PMID- 9754836
TI  - Chemistry and pharmacology of hallucinogens, entactogens and stimulants.
AB  - Amphetamines, tryptamines, phencyclidines, tetrahydrocannabinol and substances of
      the ecstasy group are characterized as stimulants, hallucinogens and entactogens.
      The various effects of each group and their mode of action in different
      transmitter systems are described. 28 new compounds of the amphetamine and
      tryptamine series has been calculated, which exceed the hallucinogenic effects of
      mescaline. The different pathways of the metabolism of MDMA (ecstasy) and MDE in
      humans may probably explain their individual effects.

PMID- 9754837
TI  - Behavioral studies of hallucinogenic drugs in animals: implications for
      schizophrenia research.
AB  - Schizophrenic and schizotypal patients exhibit deficits in the habituation and
      prepulse inhibition (PPI) of startle responses, providing operational measures of
      the sensorimotor gating or filtering deficits suggested to contribute to
      cognitive disorganization in these patients. In rats, hallucinogens, entactogens,
      and NMDA antagonists share the ability to both retard startle habituation and
      disrupt PPI. Extensive pharmacological studies in rats have indicated that the
      effects of hallucinogens on habituation are mediated by direct agonist actions at
      5-HT2 receptors. The effects of the entactogens on both habituation and PPI
      reflect indirect agonist actions due to the stimulation of presynaptic serotonin
      release. These observations in rats have supported the development of 5-HT2A
      antagonists for the treatment of schizophrenia. Animal studies have shown that
      PPI is modulated by multiple interacting neurotransmitters, including
      dopaminergic, serotonergic, cholinergic, GABAergic, and glutamatergic systems
      within cortical, limbic, striatal, and brainstem structures. The effects of PCP
      and other NMDA antagonists on PPI are insensitive to either dopaminergic or
      serotonergic antagonists, but are reduced by atypical antipsychotics such as
      clozapine, olanzapine, and Seroquel. Thus, the PCP model of schizophrenia-like
      deficits in sensorimotor gating offers promise for the identification and
      neurobiological investigation of atypical antipsychotics. The cross-species study
      of homologous gating functions, such as habituation and PPI, in animal models and
      psychiatric patients provides novel opportunities for the exploration of
      neurobiological substrates relevant to the group of schizophrenias.

PMID- 9754838
TI  - The standardized psychometric assessment of altered states of consciousness
      (ASCs) in humans.
AB  - The APZ questionnaire was developed in order to explore hypotheses on ASCs. First
      -- in a series of 11 experiments using different induction methods on N = 393
      healthy subjects -- the hypothesis was tested that ASCs have major dimensions in
      common irrespective of the mode of their induction. In the International Study on
      Altered States of Consciousness (ISASC) the external validity of the experimental
      results was assessed. The ISASC was carried out on a total of N = 1133 subjects
      in six countries. The main results of the experimental studies were corroborated
      in the field studies. The results can be summarized as follows: the common
      denominator of ASCs is described by three oblique dimensions, designated as
      "Oceanic Boundlessness (OSE)", "Dread of Ego Dissolution (AIA)" and "Visionary
      Restructuralization (VUS)". The reliability and validity of the scales are
      satisfactory. Tested versions of the APZ scales are available in English (UK,
      USA), German, Italian and Portuguese. Psychometrically as yet untested versions
      exist in Dutch, Finnish, French, Greek, Spanish and Russian. The APZ
      questionnaire has become the international standard for the assessment of ASCs,
      thus helping to integrate research. A psychometrically improved version exists in
      German (OAV questionnaire). The BETA questionnaire, which measures the dimensions
      "Vigilance Reduction (VIR)" and "Auditive Alteration (AVE)" is also available in
      German. These dimensions are most likely etiology-dependent.

PMID- 9754839
TI  - Blood flow and cerebral laterality in the mescaline model of psychosis.
AB  - The psychological, neuropsychological, and neurometabolic effects of the
      hallucinogenic agent mescaline were investigated in 12 normal male volunteers.
      Between 3 1/2 and 4 hours after drug intake, mescaline produced an acute
      psychotomimetic state, as measured by the BPRS and PDS-P. The APZ questionnaire
      revealed the specific effects of mescaline in the visual system.
      Neuropsychological effects were studied with a face/non-face decision task with
      known right hemisphere advantage, in which mescaline induced a decrease in
      functioning of the right hemisphere. In functional brain imaging using SPECT,
      mescaline produced a "hyperfrontal" pattern with an emphasis on the right
      hemisphere, which was correlated with mescaline-induced psychotomimetic
      psychopathology. Our findings question the validity of the concept of
      hypofrontality as an explanation for acute psychotic symptomatology.

PMID- 9754840
TI  - Advances and pathophysiological models of hallucinogenic drug actions in humans:
      a preamble to schizophrenia research.
AB  - Recent research into the pharmacological mechanism of hallucinogens (LSD,
      psilocybin) and dissociative anesthetics (PCP, ketamine) suggest that multiple
      neurotransmitter systems are involved in drug-induced and possibly also in
      naturally occurring psychoses. Specifically, animal models suggest that a
      dysbalance between serotonin, glutamate, and dopamine in the limbic cortico
      striato-thalamic circuitry may be critical to psychotic symptom formation. To
      test this hypothesis, psychometric measures and metabolic PET investigations were
      performed (1) with FDG to elucidate the common neuronal substrates of different
      hallucinogens, (2) with specific receptor ligands before and after pretreatment
      with specific receptor antagonists to explore the putative interactions of
      hallucinogens with various neurotransmitter systems. Our data demonstrate that
      the neuronal substrate of normal and abnormal thought and behavior is associated
      with a distributed neuronal network and with multiple interactive
      neurotransmitter systems. The data also support the view that the hallucinogen
      challenge paradigm constitutes a powerful tool for elucidating the
      pathophysiology of neuropsychiatric disorders.

PMID- 9754841
TI  - The NMDA antagonist model for schizophrenia: promise and pitfalls.
AB  - Drug models have been extensively used to study the pathophysiology of
      schizophrenia. While they provide good insight into the neurobiology of this
      disorder, they have several shortcomings, which if known, help in the
      interpretation of results. In this paper we will discuss these shortcomings in
      general, and in relation to the N-methyl D-aspartate antagonist model for
      schizophrenia. This model has recently received a great deal of attention since
      both phencyclidine and the structurally related drug ketamine, produce symptoms
      that extend beyond psychosis per se to include other symptoms associated with
      schizophrenia. In fact, subanesthetic doses of ketamine in healthy individuals
      produce not only paranoia and perceptual alterations but also thought disorder,
      negative symptoms, cognitive deficits, as well as impairment on a number of
      electrophysiologic tests known to be abnormal in schizophrenia. These effects of
      ketamine will be discussed with a particular emphasis on implications for the
      pathophysiology and therapeutics of this disorder.

PMID- 9754842
TI  - Cannabinoid/anandamide system and schizophrenia: is there evidence for
      association?
AB  - Cognitive impairments during psychotic episodes are assumed to be caused not only
      by one single putative classical neurotransmitter dysfunction but also to be due
      to an impaired equilibrium of the interaction between different neurobiological
      generators of cognitive processes. Here, the perceptual abnormalities induced by
      psychotogenic agents play a major role as tools for understanding model
      psychoses. The recently discovered cannabinoid receptor system with its
      endogenous ligand anandamide can be regarded as an extremely relevant regulation
      system, a dysfunctionality of which may explain at least one subtype of
      endogenous psychoses. The present paper discusses the possible associations
      between the endogenous anandamide/cannabinoid system and schizophrenic psychoses.
      Neuropsychological experiments with the 3-D inversion paradigm were performed in
      healthy volunteers intoxicated with delta9-Tetrahydrocannabinol (delta9-THC). The
      3-D inversion paradigm represents a visual illusion of binocular depth
      perception. Such an inversion occurs in many cases, especially when objects with
      a higher degree of familiarity (e.g. photographs of faces) are displayed. It is
      assumed that cognitive factors override the binocular disparity cues of
      stereopsis. We tested the hypothesis that, during psychotic and related
      prepsychotic states, the human CNS is unable to correct implausible perceptual
      hypotheses. Our study provides evidence of strong similarities between data
      acquired from patients, suffering from productive schizophrenic psychoses and
      delta9-THC-intoxicated healthy volunteers, as concerns disturbances in the
      internal regulation of perceptual processes.

PMID- 9754843
TI  - Methodological issues of human experimental research with hallucinogens.
AB  - Human experimental research with hallucinogenic drugs is potentially able to
      identify linking variables between the psycho(patho)logical conditions and
      neurobiological alterations involved in both pharmacologically induced and
      naturally occurring acute psychotic states. A number of methodological aspects
      should be considered when planning modern experimental studies with
      hallucinogenic drugs. The issues of subject selection, repeated measures, and
      adequate control groups are discussed in this paper. Examples of recent
      experimental studies are presented which take these aspects into account. The
      first study examined psychopathological changes, facial expression and semantic
      priming effects during a psilocybin-induced state. In the second study, semantic
      priming effects after intake of psilocybin, 3,4-methylenedioxyethylamphetamine
      (MDE), and d-methamphetamine were investigated. Results confirmed time-dependent
      effects of psilocybin and the restriction of increased priming effects in the
      psilocybin group.

PMID- 9754844
TI  - Fluvoxamine or placebo in the treatment of panic disorder and relationship to
      blood concentrations of fluvoxamine.
AB  - A six-week double-blind placebo-controlled trial of fluvoxamine was undertaken in
      46 patients suffering from panic disorder with or without agoraphobia diagnosed
      by DSM-III-R guidelines. Average daily dosage of fluvoxamine was 160 mg, with a
      highest permitted dose of 300 mg/day. Weekly evaluation included a diary in which
      the number, severity, and duration of full-blown and limited panic attacks and
      the duration and severity of anticipating fear, CAS, GAS, CGI, HAM-D, adverse
      effects and the number of capsules not taken were noted. Fluvoxamine was not
      significantly superior to placebo with regard to the main outcome criterion,
      i.e., the reduction in the number of panic attacks, but it was significantly more
      effective with regard to the diminution in the number of limited panic attacks
      and showed a tendency to significance in respect of GAS and CGI. Plasma levels of
      fluvoxamine were measured at the end of week one and at the end of the study.
      Most patients with complete remission at the end of the study were found in the
      verum group with plasma fluvoxamine levels ranging from 10 to 100ng/ml. It is
      suggested that therapeutic response might be maximized by monitoring fluvoxamine
      concentrations in blood.

PMID- 9754845
TI  - Combined treatment of schizophrenic psychoses with haloperidol and valproate.
AB  - In accordance with a previous study of adjuvant effects of the anticonvulsant
      carbamazepine (CBZ) on the neuroleptic treatment of schizophrenic psychoses, the
      effects of valproate (VPA) were tested in a randomly assigned double-blind,
      placebo-controlled study. Apart from a (statistically nonsignificant)
      psychopathological deterioration following discontinuation of VPA while on
      continuous neuroleptic mediation after four weeks and a statistically significant
      effect on "hostile belligerence", no overall therapeutic effects of the
      combination of haloperidol (HPD) with VPA were observed under controlled
      conditions. Unlike the results with CBZ, concomitant use of VPA led to an even
      higher consumption of haloperidol and biperiden and to a higher rate of
      extrapyramidal symptoms compared with the corresponding placebo group, although
      these differences did not attain statistical significance. In regard to use of
      the sedative neuroleptic chlorprothixene, there was a trend toward lower doses in
      the VPA group than in the placebo group. From these results, adjuvant effects
      like those of carbamazepine in the neuroleptic treatment of schizophrenic
      psychoses could not be confirmed for valproate in the present study. However, the
      trend toward lower doses of sedative medication and observed effects on "hostile
      belligerence" may indicate sedative and/or antimanic properties of valproate
      which have recently been demonstrated in several controlled studies.

PMID- 9754846
TI  - A risk for obstruction of the airways in the parenteral use of levomepromazine
      with benzodiazepine.
AB  - Arrhythmogenic effects of phenothiazines appear to be associated with sudden
      death, whereas respiratory complications have received little attention. In this
      report we describe 5 cases with accompanying obstruction of the airways after
      intramuscular injections of levomepromazine (LPZ), a potent sedative
      phenothiazine, in combination with intravenous injections of benzodiazepine (BZ)
      during a 3-month period in a psychiatric intensive care unit. Two out of 5 cases
      were unpredictable because obstruction of the airways occurred 2 hours or more
      after the last injection. As compared with patients who received parenteral
      (intravenous or intramuscular) injections during the same period, the dose of
      intramuscular LPZ was significantly large in the 5 cases with obstruction of the
      airways. All 5 of these cases received intramuscular LPZ 0.52 mg/kg or more. In
      contrast, there was no patient with obstruction of the airways who received only
      intramuscular LPZ, the combination of LPZ and HDL, or BZ and HDL. The occurrence
      of obstruction of the airways among patients who received both intramuscular LPZ
      and intravenous BZ was significantly higher than among patients who received
      other drug regimes. These preliminary results suggest that the intramuscular use
      of LPZ with intravenous BZ may be a risk for obstruction of the airways.

PMID- 9754847
TI  - The influence of alprazolam on the monoaminergic neurotransmitter systems in
      dysthymic patients. Relationship to clinical response.
AB  - The effects of alprazolam (1.5 mg/die) on the levels of the monoaminergic
      neurotransmitter metabolites, on the activity of the hypothalamic-pituitary
      adrenal axis and on clinical outcome in subjects with primary late-onset
      dysthymia were investigated. Drug treatment significantly decreased plasma and
      urinary cortisol levels, serotonin platelet-bound and urinary 3-methoxy-4
      hydroxyphenylglycol concentrations, while it increased plasma homovanillic acid
      (HVA) concentrations. Significant relationships were observed between
      neurochemicals and global scores or some items of the Hamilton Depression Rating
      Scale, before and after treatment. Patients responded positively (73%) to the
      therapy; clinical outcome was significantly correlated with plasma and urinary
      HVA levels. Collected data seem to support the hypothesis that central
      monoaminergic systems are in part involved in therapeutic response to alprazolam.

PMID- 9754848
TI  - Evaluation of sedative effects of single and repeated doses of 50 mg and 150 mg
      tolperisone hydrochloride. Results of a prospective, randomized, double-blind,
      placebo-controlled trial.
AB  - Sedative effects of single and repeated doses of 50 mg and 150 mg tolperisone
      hydrochloride (Mydocalm), a centrally active muscle-relaxing agent, were
      evaluated in a placebo-controlled double-blind clinical trial. A total of 72
      healthy young adults balanced by sex were randomized to receive 50 mg or 150 mg
      tolperisone hydrochloride or placebo t.i.d. for a period of 8 days. Control
      examinations were performed in the mornings of days 1 and 8 before intake of the
      morning dose and at 1.5, 4 and 6 hours postdose. The psychomotoric test battery
      used in this trial revealed no sedative effects of tolperisone hydrochloride in
      the given doses at any control examination. Subjective mood ratings quantified by
      the Welzel Colored Scales were not impaired either. The lack of differences in
      sedative potentials of tolperisone hydrochloride and placebo was confirmed by
      tests on differences and by tests on equivalence using 95% CI. The present study
      substantiates clinical experience and previous clinical trials demonstrating that
      tolperisone hydrochloride, though being a centrally active muscle relaxant, does
      not cause any sedation and does not impair reaction times.

PMID- 9754849
TI  - Choreoathetoid movements associated with rapid adjustment to methadone.
AB  - Choreatiform hyperkinesias are known to be occasional movement abnormalities
      during intoxications with cocaine but not opiates. This is a case report of
      euphoria and choreoathetoid movements both transiently induced by rapid
      adjustment to the selective mu-opioid receptor agonist methadone in an inpatient
      previously abusing heroine and cocaine. In addition, minor EEG abnormalities
      occurred. Possible underlying neurobiological phenomena are discussed.

PMID- 9754850
TI  - Severe akathisia during olanzapine treatment of acute schizophrenia.
AB  - Olanzapine is a newly developed atypical neuroleptic with a marked affinity to
      the 5-HT2, D2 and D4 dopamine receptors. Like other atypical neuroleptics
      olanzapine is considered to show a reduced prevalence of extrapyramidal side
      effects when compared to classical neuroleptic drugs. We report on three patients
      with acute schizophrenia, who developed severe akathisia during treatment with
      olanzapine (20-25 mg/d). In two of these cases akathisia resolved after
      withdrawal of olanzapine and substitution by a classical or an atypical
      neuroleptic agent, respectively. In one of these patients olanzapine was well
      tolerated when reintroduced in combination with lorazepam after complete
      remission of akathisia. In the third patient akathisia was sufficiently
      controlled by dose reduction. Akathisia is generally considered to result from D2
      dopamine receptor antagonism. In the case of atypical neuroleptics such as
      olanzapine a low but still considerable D2 dopamine receptor occupancy may be
      compensated by the 5-HT2 antagonism. However, this mechanism may fail under
      certain circumstances, in particular if D2 dopamine antagonism exceeds a certain
      threshold. One should therefore be aware of possible extrapyramidal side effects
      with olanzapine that are reduced compared to classical neuroleptic drugs but not
      completely eliminated.

PMID- 9754851
TI  - Acute clozapine overdose: plasma concentration and outcome.
AB  - Clozapine is a tricyclic dibenzodiazepine derivative that is classified as an
      "atypical neuroleptic" drug for treatment of psychotic diseases. A 19-year-old
      schizophrenic female, treated with 400 mg clozapine per day, was admitted to the
      emergency department after ingestion of 5000 mg (50 x 100 mg tablets) of
      clozapine. Clozapine plasma level 2.5 hours after ingestion was 3.8 microg/ml
      (normal range 0.2-0.7 microg/ml) and very high in gastric lavage. Contrary to
      reported cases with such high plasma concentrations the patient suffered only
      from somnolence with intermittent periods of agitation and a mild anticholinergic
      syndrome with sinus tachycardia and slight hypotension. After detoxication with
      gastric lavage and short-term administration of pyridostigmine she remained
      stable, and 24 hours after ingestion she was transferred to the psychiatric unit
      without further sequelae. To prevent late-onset complications she was carefully
      monitored for five days. The clozapine plasma level 24 hours after the first
      measurement was normal. This case and others reported in the literature confirm
      that signs and symptoms after clozapine intoxication are variable and that high
      plasma levels are not lethal in every case.

PMID- 9754852
TI  - Hepatitis caused by antidepressive therapy with maprotiline and opipramol.
AB  - There are few published reports of antidepressive therapy induced hepatotoxicity.
      In most cases antidepressants cause only slight elevation of liver enzymes
      without clinical relevance. However, our patient with recidivation of unipolar
      depressive disorder developed severe laboratory abnormalities and clinical
      symptoms during therapy with maprotiline (Ludiomil) and opipramol (Insidon). To
      our knowledge, this is the first case report of bioptically proven severe acute
      hepatitis caused by these antidepressants. After their withdrawal, the patient's
      fatigue symptoms, scleric jaundice, and marked increase of liver enzymes
      completely disappeared. Hepatic side effects should be considered during
      antidepressive therapy with maprotiline and opipramol especially when additional
      clinical symptoms emerge.

PMID- 9754853
TI  - Clozapine treatment of HIV-associated psychosis--too much bone marrow toxicity?

PMID- 9754854
TI  - Solving mysteries of the bioeffects of nonionizing radiation.

PMID- 9754855
TI  - Biological effects of amplitude-modulated radiofrequency radiation.
AB  - Users of mobile telephones are exposed to radiofrequency radiation. One of the
      questions still open today is whether amplitude-modulated radiofrequency signals
      from digital phones exert specific bioeffects different from those of continuous
      (unmodulated) radiofrequency radiation. This paper reviews recent literature on
      the bioeffects of amplitude-modulated radiofrequency radiation, from cells to
      humans. The consistency of the results is discussed, and exposure parameters are
      compared to identify possible biologically active forms of amplitude modulation.
      Several studies have reported findings consistent with effects on the nervous
      system and cancer-related biological processes. However, the methods and exposure
      parameters vary widely, and no independent replications of the positive findings
      have been reported. The results available today fail to support the existence of
      well-defined modulation-specific bioeffects from exposure to radiofrequency
      radiation. Additional systematic studies are needed to identify possible
      reproducible modulation-dependent effects and biologically active modulation
      parameters.

PMID- 9754856
TI  - Meta-analyses of non-Hodgkin's lymphoma and farming.
AB  - OBJECTIVES: This study examined the association between non-Hodgkin's lymphoma
      (NHL) and farming. METHODS: A series of meta-analyses of peer-reviewed studies
      was performed using 36 studies published between 1982 and 1997. Prior to the meta
      analyses, all the studies were reviewed and evaluated for heterogeneity and
      publication bias. Combined relative risks (RR) were calculated using the random
      effect model. RESULTS: The combined RR was 1.10 [95% confidence interval (95% CI)
      1.03-1.19] for all the studies and 0.93 (95% CI 0.82-1.06) for studies involving
      female farmers. Significant heterogeneity was detected for study design and
      country of study among the studies. Significantly elevated RR values were
      obtained for case-referent studies (combined RR 1.19, 95% CI 1.06-1.33) and for
      studies conducted on farmers residing in the United States (combined RR 1.26, 95%
      CI 1.15-1.37). These findings were not influenced by a publication bias.
      CONCLUSIONS: The findings suggest that male farmers residing in the United States
      have a slightly elevated risk of contracting NHL. Commonly experienced exposures
      that might contribute to the occurrence of NHL in this group include infectious
      microorganisms, herbicides, and insecticides.

PMID- 9754857
TI  - Determinants of asthma in a farming population.
AB  - OBJECTIVES: This study examined the determinants of asthma in a population of
      farmers, including as a crude indicator of genetic predisposition "history of
      asthma in next-of-kin" (family history), and exposure factors such as animal
      production and smoking. METHODS: In a cross-sectional study of 8482 farmers or
      farmers' spouses in Norway a questionnaire with information on asthma among the
      subjects and their next-of-kin, production type and farming activities, exposures
      outside farming, and smoking was applied. Spirometry was performed. RESULTS: The
      lifetime prevalence of self-reported asthma in the population was 6.3%.
      Significant risk factors for current asthma were asthma among next-of-kin, asthma
      as child or adolescent, animal production, and age. In a comparison with subjects
      with no family history of asthma and no animal production the adjusted odds ratio
      for current asthma in never smokers was 1.9 [95% confidence interval (95% CI) 0.4
      8.9] for subjects with family history only, 2.2 (95% CI 1.1-4.2) for subjects
      with animal production only, and 6.3 (95% CI 3.1-13.1) for subjects with both
      factors. A combination of animal production, smoking, and a positive family
      history gave an odds ratio of 8.1 (95% CI 4.0-16.2) for current asthma.
      CONCLUSIONS: The study can be interpreted as support for the hypothesis of an
      interaction between genetic factors and exposure factors in the causation of
      asthma. Since familial associations may be exposure-related, the necessity of
      considering indicators of both inheritance and exposure in epidemiologic studies
      of asthma is emphasized.

PMID- 9754858
TI  - Mortality and cancer incidence among Swedish paint industry workers with long
      term exposure to organic solvents.
AB  - OBJECTIVES: The aim of this update on a cohort of male paint industry workers was
      to determine whether an excess of mortality and incidence of lymphatic and
      hematopoietic tumors, particularly multiple myeloma, still exists, and, if so, to
      determine if it is due to exposures occurring before the mid-1950s, when benzene
      disappeared as a solvent in the Swedish paint industry. METHODS: The cohort of
      411 men who had worked in the Swedish paint industry and had been exposed to
      organic solvents for at least 5 years during 1955-1975 was followed from 1961 to
      1994 for causes of death in the mortality register and from 1961 to 1992 for
      cases of cancer in the Swedish cancer register. RESULTS: The number of paint
      industry workers who had died, plus the number of deaths in the major disease
      groups and the number of cancers reported to the cancer registry, was close to
      the expected. The incidence of prostatic cancer increased somewhat [standardized
      incidence ratio (SIR) 1.5, 95% confidence interval (95% CI) 1.0-2.2]. Among the
      workers first employed in 1956 or earlier, there was an increase in both the
      incidence and mortality from all lymphatic and hematopoietic tumors [SIR 2.3, 95%
      CI 1.0-2.2; standardized mortality ratio (SMR) 2.0, 95% CI 0.7-4.4]. The excess
      was particularly marked for multiple myeloma (SIR 3.8, 95% CI 0.8-11; SMR 4.4,
      95% CI 0.9-13). CONCLUSIONS: Employment in the Swedish paint industry before 1957
      may have entailed some excess risk of lymphatic and hematopoietic tumors,
      particularly multiple myeloma. A significant excess of prostatic cancer was not
      linked to any particular employment period and deserves further investigation.

PMID- 9754859
TI  - Immunologic and renal markers among photogravure printers exposed to toluene.
AB  - OBJECTIVES: This study assessed immunologic and early renal effects of chronic
      toluene exposure. METHODS: In a longitudinal study of 92 printers and 74
      referents, 145 subjects had pre- and poststudy samples of blood and urine taken
      for the following measurements: immunoglobulin E (IgE), antiglomerular basement
      membrane (anti-GBM) and antilaminin (anti-LAM) antibodies in blood; creatinine
      and beta2-microglobulin in blood and urine; and microalbumin, N-acetyl-b-D
      glucosaminidase (NAG) and alanine-aminopeptidase in urine. Creatinine clearance
      was calculated according to the Cockroft-Gault formula. Eight-hour personal air
      samples were collected twice to assess present exposure to toluene. A job
      exposure matrix was developed to estimate past cumulative exposure. Information
      about potential confounders was recorded by questionnaire. Multiple regression
      analysis was performed to study dose-effect relations adjusted for age and
      smoking. RESULTS: No subject was positive for anti-GBM antibodies, and only 12
      were positive for anti-LAM. No relation was observed between the markers studied
      and present exposure to toluene except that creatinine clearance was higher among
      the exposed subjects than among the referents. A dose-response relation was
      observed between cumulative toluene exposure and both IgE and NAG excretion. No
      interaction was observed between hypertension and exposure, but the relationship
      with NAG did not persist when subjects with hypertension were excluded. Past or
      present exposure did not alter the 2-year trend of any marker studied.
      CONCLUSIONS: According to the results of this study, toluene at 50 ppm is not
      related to detectable renal dysfunction. The increased IgE levels associated with
      present and past exposure require further investigation.

PMID- 9754860
TI  - Occurrence of carpal tunnel syndrome among slaughterhouse workers.
AB  - OBJECTIVES: The aim of this study was to examine the risk of carpal tunnel
      syndrome (CTS) among workers with daily occupational exposure to high-force and
      high-velocity manual work. METHODS: The study was carried out retrospectively
      among a cohort of 1591 workers employed at a slaughterhouse or at a chemical
      factory; 1141 persons (71.7%) participated. Workers not doing tasks in
      slaughtering or meat processing constituted the reference group. Exposure
      assessments were made for 46 different tasks in slaughtering and meat processing
      from video-based observations at the workplace. CTS was diagnosed if there were
      current symptoms typical of CTS in combination with positive neurophysiological
      signs of CTS or if the subject had previously been operated on for CTS. RESULTS:
      Altogether 1.6% of the reference group, 5.1% of the nondeboning slaughterhouse
      workers [prevalence ratio (PR) 3.23, 95% confidence interval (95% CI) 1.3-7.99]
      and 7.8% of the deboning slaughterhouse workers (PR 4.91, 95% CI 2.03-11.81) had
      CTS. Increased risk estimates persisted after adjustment for other potential risk
      factors by logistic regression. The prevalence of CTS in the dominant hand was
      equally increased in both groups of slaughterhouse workers (but only
      statistically significant for the workers in deboning tasks), while the
      prevalence of CTS in the nondominant hand was significantly increased only among
      the slaughterhouse workers in deboning tasks. CONCLUSIONS: This study supports
      the hypothesis that daily high-velocity and high-force manual work is a risk
      factor for CTS.

PMID- 9754861
TI  - From a unidimensional to a bidimensional concept and measurement of workers'
      safety behavior.
AB  - OBJECTIVES: This study examines the concept and measurement of worker's safety
      behavior. It shows that the traditional concept of safety behavior centered on
      workers' carefulness or compliance with safety rules is limited and proposes that
      an additional dimension, namely, workers' safety initiatives, be taken into
      account. METHODS: Confirmatory factor analyses were carried out for a random
      sample of 828 workers drawn from 9 manufacturing facilities located in the
      province of Quebec (Canada). RESULTS: A 2-correlated congeneric factor model gave
      parameters in the expected direction, but the overall model was unable to reach a
      good fit. Separate construct analyses showed that compliance with safety rules is
      not a consistent dimension. The safety-initiatives dimension achieved a good fit
      with a high composite reliability (p=0.85). CONCLUSIONS: Workers' compliance with
      safety rules was not structured as a unitary dimension; therefore a selective
      process of safety-rules compliance by workers is suggested. Each category of
      safety rules should be considered as 1 single dimension and measured by several
      specific indicators. Indicators for safety initiatives provide high reliability,
      and, since this dimension is an important predictor of effectiveness in accident
      prevention, the items tested provide a better measurement than those previously
      published.

PMID- 9754862
TI  - Combined effects of shift work and life-style on the prevalence of insomnia,
      sleep deprivation and daytime sleepiness.
AB  - OBJECTIVES: The combined effects of age, leisure-time physical activity, smoking,
      alcohol consumption, and different forms of shift work on the prevalence of sleep
      complaints and daytime sleepiness were studied among workers in industry,
      transport, and traffic. METHODS: Altogether 3020 subjects were studied using a
      psychosocial questionnaire. The participants were currently employed men, aged 45
      60 years, from a postal and telecommunication agency, the railway company, and 5
      industrial companies. On the basis of a factor analysis of an 11-item sleep
      questionnaire, the sleep complaints were grouped into the categories of insomnia,
      sleep deprivation, daytime sleepiness, and snoring. The importance of the shift
      schedule, age, and life-style factors as simultaneous predictors of the
      complaints was studied in a logistic regression analysis and an analysis of
      covariance. RESULTS: The prevalence of insomnia, sleep deprivation, and daytime
      sleepiness depended significantly on the shift system. All sleep complaints were
      more common in 2- and 3-shift work and in irregular shift work than in day work.
      The prevalence of daytime sleepiness was 20-37%, depending on the shift system.
      Leisure-time physical activity and alcohol consumption were the most important
      life-style factors predicting all sleep complaints, except snoring. The effects
      of physical activity and alcohol consumption differed for different shift
      schedules. CONCLUSIONS: Different shift systems, also 2-shift work and permanent
      night work, seem to increase the frequency of sleep complaints. Especially 3
      shift work seems to interact with life-style factors by increasing the adverse
      effects and decreasing the beneficial effects on sleep and sleepiness.

PMID- 9754863
TI  - Experience with a vocabulary test for workers previously and still exposed to
      styrene.
AB  - OBJECTIVES: This study examined the possible influence of styrene exposure on the
      results of vocabulary tests because verbal ability is assumed to be relatively
      resistant to the toxic effects of organic solvents and short vocabulary tests are
      used as "hold tests" in many neurobehavioral epidemiologic studies, METHODS: To
      evaluate the chronic neurotoxic effects of styrene, a vocabulary test was
      administered to a group of still-exposed workers (N=27) and an earlier exposed
      group of workers (N=90). A self-administered questionnaire was filled out on life
      events, general health, educational level, and amount of education. The still
      exposed group had a mean exposure duration of 4700 hours, and that for the
      formerly exposed group was 3610 hours. RESULTS: The vocabulary score of the still
      exposed group was significantly lower [12.5 (SD 2.9, range 6-18)] than that of
      their former colleagues [14.3 (SD 3.4, range 8-22)], even though they originally
      belonged to the same group and had done the same tasks. The exposure duration
      explained a significant part of the vocabulary results, resulting in decreasing
      vocabulary scores even when the influence of years of education and age was taken
      into account. Even after correction for the possible influence of having been
      laid off or staying at work, there remained a negative influence on the
      vocabulary score for the duration of styrene exposure. CONCLUSIONS: The use of
      short vocabulary tests as hold tests in cross-sectional studies of solvent
      exposed workers may be limited as they seem to lack the essential toxicity
      independent property.

PMID- 9754864
TI  - Towards the coordination of European research on the carcinogenic effects of
      asbestos.

PMID- 9754865
TI  - Ligation of selectin L and integrin CD11b/CD18 (Mac-1) induces release of
      gelatinase B (MMP-9) from human neutrophils.
AB  - OBJECTIVE AND DESIGN: To examine whether ligation of the adhesive receptors -
      selectin L and Mac-1 on the neutrophil surface could induce gelatinase B
      exocytosis. MATERIALS: Neutrophils were isolated from fresh heparinized blood of
      human donors by Gradisol G centrifugation and hypotonic lysis of erythrocytes.
      METHODS: Integrin CD1 1b/CD18 and selectin L mediated adhesive interaction of
      human neutrophils were mimicked by binding antibodies to these receptors on the
      surface of isolated leukocytes. Neutrophils (5 x 10(6)/ml) were incubated with
      antibodies against selectin L (40/microg/ml) and CD18 or CDI 1b (10microg/ml).
      The secretion of gelatinase was examined by determination of enzyme activity and
      gelatin substrate zymography of cell supernatants. RESULTS: Ligation of selectin
      L, CD18 and CD11b integrin subunits by monoclonal antibodies induced a rapid
      release of 24.6+/-1.8% (p<0.005), 24.0+/-2.9% (p<0.001) and 22.7+/-2.0% (p <
      0.005) of total neutrophil gelatinase, respectively as compared with 11.1+/-1.6%
      in the control. These values were equivalent to N-formyl-methionylleucyl
      phenylalanine (fMLP)-stimulated secretion of gelatinase. Under these experimental
      conditions there was no significant beta-glucuronidase release from azurophilic
      granules. Gelatinase exocytosis elicited by selectin L and CD18 ligation was
      inhibited by 82.7+/-10.1% and 49.3+/-5.9%, respectively after preincubation of
      the neutrophils with 10 microM herbimycin A. CONCLUSIONS: Ligation of selectin L
      and integrin CD11b/ CD18 provides stimulatory signals to neutrophils which induce
      secretion of gelatinase B that may facilitate their transmigration into sites of
      inflammation.

PMID- 9754866
TI  - Ca2+-ATPase inhibitors and PKC activation synergistically stimulate TNF-alpha
      production in RBL-2H3 cells.
AB  - OBJECTIVE AND DESIGN: To investigate the effect of Ca2+-ATPase inhibitors on the
      production of TNF-alpha in rat basophilic leukemia (RBL-2H3) cells. MATERIAL: Two
      Ca2+-ATPase inhibitors, thapsigargin (TG) and cyclopiazonic acid (CPA), and three
      hydroquinone-antioxidants, 2,5-di-(tert-butyl)-1,4-hydroquinone (DTBHQ), 2,5-di
      (tert/amyl)-1,4-hydroquinone (DTAHQ), 2-(tertbutyl)-1,4-hydroquinone (MTBHQ) were
      used. TREATMENT: Cells were treated with TG, CPA, DTBHQ, DTAHQ and MTBHQ for 3 h
      in the presence of 12-Otetradecanoylphorbol-13-acetate (TPA) and released TNF
      alpha from the cells was measured (n > or = 4). RESULTS: All Ca2--ATPase
      inhibitors (TG, CPA, DTBHQ and DTAHQ) induced TNF-alpha release in a dose
      dependent manner. TNF-alpha release was inhibited by treatment with protein
      kinase C inhibitors (staurosporine, Ro31-8220, calophostin C) (p < or = 0.05). In
      contrast, MTBHQ, which does not induce increases in [Ca2+]i, did not induce the
      release of TNF-alpha. TNF-alpha release induced by DTBHQ and CPA was inhibited by
      treatment with actinomycin-D, the immunosuppressant FK506 and the glucocorticoid
      dexamethasone (p < or = 0.01). CONCLUSIONS: These results suggest 1) that [Ca2+]i
      increase and subsequent activation of protein kinase C is necessary for the
      release of TNF-alpha, and they work synergistically, 2) that the TNF-alpha
      release induced by Ca2+-ATPase inhibitors can be regulated at the transcriptional
      level.

PMID- 9754867
TI  - Further studies on anti-inflammatory activity of phycocyanin in some animal
      models of inflammation.
AB  - OBJECTIVE: To examine the effects of C-phycocyanin, a pigment found in blue-green
      algae which acts as an antioxidant in vitro and in vivo, in different animal
      models of inflammation. MATERIAL: Male Sprague Dawley rats and OF1 mice were
      used. TREATMENTS: Oedema was induced by: a) AA (0.5 mg/ear) or TPA (4 microg/ear)
      in the mouse ear b) carrageenan injection (0.1 mL of 1% suspension) in the rat
      paw (+/-adrenalectomy) and c) cotton pellet implantation in the rat axilla.
      Phycocyanin (50-300mg/kg, p.o.) or indomethacin (1 mg/ear or 3-10mg/kg, p.o.) as
      control were tested in the four animal models. METHODS: Measurement of the
      increase in the weight (mg) of 6 mm ear punch biopsies from treated ears were
      made in comparison to control ears, together with myeloperoxidase (MPO) activity
      as an index of neutrophil infiltration. The increase in the paw thickness (mm)
      was measured with a dial caliper. Cotton pellet was implanted and seven days
      afterwards the granuloma was removed and the dry weight was determined. Acute
      toxicity was studied in mice and rats. Statistics were performed using one-way
      analysis of variance with the Duncan Multirange test. RESULTS: Phycocyanin
      reduced significantly (p < 0.05) and in a dose-dependent manner ear oedema
      induced by AA and TPA in mice as well as carrageenan-induced rat paw oedema (both
      in intact and adrenalectomized animals). In the TPA test, phycocyanin also
      reduced MPO content. Phycocyanin also exerted an inhibitory effect in the cotton
      pellet granuloma test. In the acute toxicity test in rats and mice, even at the
      highest dose tested (3000 mg/kg, p.o.), no toxicity was found. CONCLUSIONS:
      Phycocyanin shows anti-inflammatory activity in four experimental models of
      inflammation. Its antioxidative and oxygen free radical scavenging properties may
      contribute, at least in part, to its anti-inflammatory activity.

PMID- 9754868
TI  - Sirolimus (rapamycin, Rapamune) and combination therapy with cyclosporin A in the
      rat developing adjuvant arthritis model: correlation with blood levels and the
      effects of different oral formulations.
AB  - OBJECTIVE AND DESIGN: To determine whole blood levels of sirolimus, a macrolide
      antibiotic in the rat developing adjuvant arthritis (AA) model after dosing
      orally with two different vehicles, and whether combinational doses of sirolimus
      and cyclosporin A (CsA) produced additive or synergistic inhibitory effects in
      this model. MATERIAL: Male Lewis rats (150-180g). TREATMENT: Arthritis was
      induced by the injection (0.5 mg/ rat) of heat-killed Mycobacterium butyricum
      suspended in light mineral oil. Drugs were administered orally either in fine
      suspension (0.5% Tween 80) or in emulsion (phosal 50 PG in 1% Tween 80) at doses
      of 0.1 to 5 mg/kg in a 7 day, MWF or daily regimen. METHOD: Paw volumes (ml) were
      measured by automated mercury plethysmograph and sirolimus concentrations in
      whole blood were quantitated by liquid chromatography/ mass spectroscopy.
      RESULTS: At 72h (7 days after adjuvant) after receiving the third oral dose (4.5
      mg/kg p.o.), the phosal vehicle resulted in higher sirolimus blood levels (2.5
      ng/ml) than in Tween 80 (1.6 ng/ml). After the rats received the last oral dose
      on day 14, (7 total doses of sirolimus at 4.5 mg/kg) the sirolimus blood levels
      (2h after the last dose) were about 2 times higher for the phosal dosed rats (9.8
      ng/ml) compared to Tween 80 dosed rats (4.6ng/ml). Even 24h after the last dose,
      sirolimus blood levels were still elevated in the phosal dosed rats (0.8 ng/ml)
      relative to 0.5% Tween 80 dosed rats (0.5 ng/ml). At day 16 in the rat developing
      model, sirolimus, when given in phosal vehicle, produced an ED50 of 0.28 mg/ kg
      (i.e. inhibition of uninjected paw edema) that was about 5.5 times lower than
      using 0.5% Tween 80 as the suspending agent (ED50 = 1.6mg/kg). When combining
      sirolimus and CsA using precalculated doses for producing an additive effect in
      this adjuvant model, an additive inhibitory effect on uninjected paw edema was
      observed at equal combinational doses of 0.5 and 2 mg/kg, respectively.
      CONCLUSIONS: The phosal vehicle used in administering sirolimus increases the
      absorption and whole blood levels in the rat and the elevated blood levels
      correlated positively with the therapeutic effect in the rat developing AA model.
      In addition, combination therapy using sirolimus and CsA produced an additive
      effect in rat developing AA.

PMID- 9754869
TI  - Activation of neutrophil respiratory burst by cytokines and chemoattractants.
      Regulatory role of extracellular matrix glycoproteins.
AB  - OBJECTIVE AND DESIGN: We investigated the in vitro responsiveness of neutrophils
      adherent to fibronectin (FN) and laminin (LM), toward natural pro-inflammatory
      and/or phagocyte-activating agents. MATERIALS AND METHODS: Neutrophils from
      normal volunteers were layered on polystyrene wells precoated or not with FN
      and/or LM and tested for their ability of responding to eleven pro-inflammatory
      mediators by evaluation of superoxide anion (O2-) production and adherence.
      Results, expressed as mean +/-1SEM, were evaluated by non-parametric analyses
      (Mann-Whitney U-test or Kruskal-Wallis non-parametric ANOVA analysis) RESULTS:
      Precoating polystyrene wells with LM or FN prevented the plastic-induced
      neutrophil (O2-) production. Among eleven agents, tumor necrosis factor-alpha
      (TNF, 3.0+/-0.3 nmoles (O2-)/5 x 10(4) neutrophils/180 min, p < 0.001),
      granulocyte-macrophage colony stimulating factor (GM-CSF, 2.1+/-0.3 nmoles (O2
      )/5 x 10(4) neutrophils/180 min, p < 0.05) and formyl-peptides (fMLP, 2.5+/-0.5
      nmoles (O2-)/5 x 10(4) neutrophils/180min, p < 0.01) caused massive (O2-)
      production by neutrophils adherent to FN. None of the mediators was capable of
      triggering (O2-) production by neutrophils adherent to LM. LM, mixed with FN to
      coat wells, caused a dose-dependent inhibition of the oxidative burst triggered
      by TNF (IC50 LM: 0.84+/-0.03 microg, mean+/-1 SEM), GM-CSF (IC50 LM: 0.36+/
      0.16micro/g, mean+/-1SEM) and fMLP (IC50 LM: 0.54+/-0.008 microg, mean+/-1 SEM).
      To the contrary, fMLP (85.5+/-27.7%), TNF (163.1+/-67.5%), and GM-CSF (121.8+/
      66.4%) caused a significant augmentation of neutrophil adherence to LM,
      suggesting that LM-mediated inhibition of neutrophil oxidative metabolism does
      not depend on the concomitant LM-induced inhibition of neutrophil adherence.
      Finally, neither solid-phase FN nor LM affected (O2-) production by neutrophils
      in response to immune complexes. CONCLUSIONS: Extracellular matrix glycoproteins
      dictate the response of neutrophils to soluble mediators but not to immune
      complexes. This appears to be a biologically meaningful mechanism to localise the
      risk of cellular reactions to mediators that are able to diffuse easily from
      tissue sites of generation and become widely distributed in body fluids during
      inflammatory diseases.

PMID- 9754870
TI  - Increased release of ATP from endothelial cells during acute inflammation.
AB  - OBJECTIVE AND DESIGN: The effects of lipopolysaccharide (LPS), a potent
      inflammatory mediator, on the shear stress stimulated release of adenosine
      triphosphate (ATP) were investigated on endothelial cells from human umbilical
      vein in primary culture. METHODS: Human umbilical vein endothelial cells (HUVEC)
      in primary cultures were subjected to shear stress using a cone and plate
      apparatus. ATP released by the cells was measured by luminometry, using a
      luciferin-luciferase assay. RESULTS: Under conditions of shear stress alone
      (25dyn/cm2), ATP accumulates into the culture medium and reaches a maximum after
      3 to 5 min of stimulation (121.7+/-13.2 pmol/ml). The shear stress-stimulated
      release of ATP was significantly increased after a 4 h pre-incubation of
      endothelial cells with 50 microg/ml (314.4+/-26.7 pmol/ml) and 10microg/ml
      lipopolysaccharide (207.7+/-22.2 pmol/ml). Dexamethasone, an anti-inflammatory
      glucocorticoid, inhibited the effects of lipopolysaccharide. CONCLUSIONS: These
      results show that non-damaged endothelial cells release ATP under experimental
      inflammatory conditions and support an early role of extracellular ATP in the
      inflammatory process.

PMID- 9754871
TI  - Genetic lesions in Drosophila behavioural mutants.
AB  - Over the last 30 years, several hundred behavioural mutants have been isolated in
      Drosophila. Only a fraction of these are well characterized genetically,
      behaviourally, and structurally. From six areas of behaviour a set of 24 well
      studied mutants was chosen, in which the behavioural defect is probably caused by
      a central dysfunction and not by an impairment of sensory input or motor output.
      In all cases, the affected genes can be mutated to more than just a behavioural
      phenotype. Most genes in the sample are essential. Thus, phenotypic specificity
      is caused by the specificity of the mutation and not by the gene being a
      'behavioural gene'. This study investigates how partial functional inactivation
      in these loci is brought about genetically. In particular, an attempt is made to
      discern whether behavioural mutations affect part of a protein's functional
      repertoire, a subset of protein isoforms, or the spatio-temporal expression of a
      gene. Not unexpectedly, in view of the predominant use of ethyl methanesulfonate
      (EMS) as mutagen, the majority of sampled mutations fall into the first two
      categories. The potentially richest source of genetic versatility, the spatio
      temporal modulation of promoter activity by enhancers and silencers, has thus
      been insufficiently exploited for obtaining behavioural mutants. Various mutagens
      are reviewed as to their suitability in inducing selective regulatory mutations.

PMID- 9754872
TI  - The cerebellum and postural sensorimotor learning in mice and rats.
AB  - Animals with cerebellar damage caused by gene mutations, surgical ablations and
      irradiation by X-rays during developmental stages are impaired in maintaining
      posture and equilibrium. For most tests, even in animals with total
      cerebellectomy, postural sensorimotor learning is not abolished. Simpler
      compensatory movements may be adopted. The acquisition of simple sensorimotor
      skills occurring after massive damage of the cerebellar cortex may be explained
      by the modulatory role of the cerebellar deep nuclei during learning processes or
      by the influence of extracerebellar regions taking over lost cerebellar function.

PMID- 9754873
TI  - The foraging gene affects adult but not larval olfactory-related behavior in
      Drosophila melanogaster.
AB  - This study investigates the ability of larvae and adult rover and sitter
      Drosophila melanogaster to detect and migrate towards the source of a fly medium
      attractant using larval plate assays and an adult olfactory trap assay. Allelic
      variation at the foraging locus which encodes a cGMP-dependent protein kinase
      (PKG) did not affect larval olfactory response in the larval plate assays. In
      contrast, adult males of the sitter mutant for(s2) exhibited an olfactory trap
      response (OTR) which was significantly greater than that of males of the wild
      type forR strain from which for(s2) was derived and further genetic analysis
      showed that this was attributable to the for(s2) allele. The olfactory responses
      of fbrR and for(s2) flies to three odours (propionic acid, ethyl acetate and
      acetone) in a T-maze assay was normal indicating that they did not have general
      olfactory deficits. The finding that adult flies who differ in their PKG enzyme
      activities differ in foraging behaviours and olfactory trap responses to yeast
      odours suggests that PKG signalling pathways are involved in olfactory related
      responses to food.

PMID- 9754874
TI  - New functions for nicotinic acetylcholine receptors?
AB  - Although the neuronal nicotinic acetylcholine receptor is found in most parts of
      the brain, not much is known about its functional significance. At least ten
      different subunits are expressed in the central nervous system, theoretically
      able to give rise to more than a thousand different receptor subtypes. Despite,
      or perhaps because of, this astonishing diversity, the biological role of this
      receptor type remains to be investigated. It has recently been found that a
      mutated alpha4-subunit is associated with an inherited epilepsy syndrome. A
      missense mutation replacing a serine in position 248 of the second transmembrane
      domain by phenylalanine leads to hypoactivity of the receptor due to accelerated
      desensitization and delayed resensitization. Thus, for the first time a link
      between a human disease and a mutated neuronal nicotinic acetylcholine receptor
      has been found, pointing to a possible involvement of this ligand-gated receptor
      family in the modulation of brain excitability levels.

PMID- 9754875
TI  - Multiple behavioral anomalies in GluR2 mutant mice exhibiting enhanced LTP.
AB  - We have previously disrupted the ionotropic glutamate receptor type 2 gene
      (GluR2) using gene targeting in embryonic stem cells and generated mice which
      lacked the GluR2 gene product. Neurophysiological analyses of these mice showed a
      markedly enhanced long-term potentiation (LTP) and a 9-fold increase in kainate
      induced Ca2+ permeability in the hippocampus. Here, we analyze the behavioral and
      neuroanatomical consequences of GluR2 deficiency in homozygous null mutant and
      age-matched littermate control mice. We show that despite unaltered gross brain
      morphology, several aspects of behavior were abnormal in the mutants. Object
      exploration, rearing, grooming and locomotion were altered in the novel arena.
      Eye-closure reflex, motor performance on the rotating rod and spatial and non
      spatial learning performance in the water maze were also abnormal in the mutants.
      These abnormalities together with the widespread expression pattern of GluR2 in
      most excitatory CNS pathways suggest that the absence of GluR2 leads to
      neurological phenotypes associated with not only the hippocampus but several
      other brain regions potentially including the cortex and cerebellum. We speculate
      that GluR2 mutant mice suffer from an overall non-specifically increased
      excitability that may alter cognitive functions ranging from stimulus processing
      to motivation and learning.

PMID- 9754876
TI  - A 2-year longitudinal study of swimming navigation in mice devoid of the prion
      protein: no evidence for neurological anomalies or spatial learning impairments.
AB  - Uncontrolled accumulation of a conformationally distorted protein (PrP(Sc)) is
      supposed to be the pathological process leading to spongiform encephalopathy.
      Targeted disruptions of the Prn-P gene in the mouse have resulted in animals that
      did not show anomalies in spatial and avoidance learning and were resistant to
      experimental infections. However, another Prn-P knockout mouse was reported to
      show ataxia and Purkinje cell degeneration developing after 70 weeks of age. In
      this study the initial observations are confirmed on swimming navigation of PrP
      null mutant mice using an enlarged sample of 58 mice. A representative subsample
      of 16 mice was then followed up for their ability of swimming navigation up to an
      age of two years (104 weeks). Surviving PrP-null mutants (n = 4) and controls (n
      = 6) did not differ in any measure, nor were there indications of ataxia and
      Purkinje cell degeneration. It was concluded that the PrP-knockout mice used by
      Bueler et al. were probably normal with respect to aging processes and that
      resistance to scrapie is not necessarily paid for by late neuronal degeneration.
      The reasons for the discrepancy between different knockout experiments require
      experimental clarification, however.

PMID- 9754877
TI  - Transgenic mice expressing an alpha-secretion mutant of the amyloid precursor
      protein in the brain develop a progressive CNS disorder.
AB  - Expression of alpha-secretion mutant APP/RK in mouse brain results in a
      progressive disorganization of the central nervous system, exemplified by
      behavioral deficits, premature death and neuropathology. Here we report on the
      progressive nature of this CNS disorder as indicated by the age dependency of the
      neophobic reaction in the open-field test. The earlier reported NMDA hypo
      sensitivity in the transgenic APP/RK mice is likely to represent a subtle
      functional disturbance, since no changes in NMDA receptor density or distribution
      could be detected. None of the typical neuropathological hallmarks of Alzheimer's
      Disease, i.e. amyloid deposits and neurofibrillary tangles are detected in the
      brain of these transgenic mice. Nevertheless, the progressive CNS disorder
      elicited in the transgenic APP/RK mice recapitulates certain features and
      symptoms of patients with Alzheimer's disease as discussed.

PMID- 9754879
TI  - The genetic basis of the relation between speed-of-information-processing and IQ.
AB  - The relationship of speed-of-information-processing (SIP), as derived from
      reaction times (RTs) on experimental tasks, and intelligence has been extensively
      studied. SIP is suggested to measure the efficiency with which subjects can
      perform basic cognitive operations underlying a wide range of intellectual
      abilities. Observed phenotypic correlations between RT and IQ typically are in
      the -0.2 to -0.4 range, and the question is addressed to what extent this
      relationship is determined by genetic or environmental influences. In a group of
      Dutch twins the heritabilities for RT tasks at age 16 and 18 years were estimated
      longitudinally and the nature of the RT-IQ relationship was investigated. At age
      16 years heritabilities for a simple reaction time (SRT) and choice reaction time
      (CRT) were 64 and 62% and the average phenotypic correlations between the RTs and
      IQ, assessed by the Raven standard progressive matrices, was -0.21. At the second
      test occasion lower heritabilities were observed for the RTs, probably due to
      modifications in administration procedures. The mean correlations between the RTs
      and WAIS verbal and per formal subtests were -0.18 and -0.16. Multivariate
      genetic analyses at both ages showed that the RT-IQ correlations were explained
      by genetic influences. These results are in agreement with earlier findings
      (Baker et al., Behav Genet 1991;21:351-67; Ho et al., Behav Genet 1988;18:247-61)
      and support the existence of a common, heritable biological basis underlying the
      SIP-IQ relationship.

PMID- 9754878
TI  - Neurobehavioral development, adult openfield exploration and swimming navigation
      learning in mice with a modified beta-amyloid precursor protein gene.
AB  - The processing of beta-amyloid precursor protein (betaAPP) and its metabolites
      plays an important role in the pathogenesis of Alzheimer's disease (AD) and
      Down's syndrome. The authors have reported elsewhere that a targeted mutation
      resulting in low expression of a shortened betaAPP protein (betaAPP(delta/delta))
      entails reduced learning abilities. Here the authors investigate whether these
      effects were caused by postnatal developmental actions of the altered protein.
      The authors examined 35 mice carrying the betaAPP(delta/delta) mutation for
      somatic growth and sensorimotor development during the first 4 postnatal weeks
      (pw) and compared them with 31 wildtype litter-mates. Thereafter, the same mice
      were tested at about 10 weeks of age for openfield behavior and for swimming
      navigation learning. Mutant mice showed both transient and long-lasting deficits
      in development. Body weight deficit started to emerge at postnatal day (pd) 12,
      peaked with a 15.1% deficit at pd 27 and lasted until pw 33-37. Significant
      transient deficits in mutant mice during sensorimotor development were observed
      in three time windows (pd 3-10, pd 11-19 and pd 20-27), long-lasting effects,
      manifest at pw 8-12 and pw 33-37, emerged at any of the three periods. In the
      adult mice, exploratory activity of betaAPP mutants in the openfield arena was
      severely reduced. In the Morris water maze task, mutant mice showed moderate
      escape performance deficits during the acquisition period but no impairment in
      spatial memory. The authors conclude that a defective betaAPP gene impairs
      postnatal somatic development, associated with transient as well as long-lasting
      neurobehavioral retardation and muscular weakness. Comparison with earlier data
      suggests that early postnatal handling may attenuate some of the non-cognitive
      performance deficits in the water maze. Further, the manifestation and time
      course of behavioral yet not neuropathological symptoms in betaAPP mutant mice
      resemble in some aspects those of the human Down's syndrome.

PMID- 9754880
TI  - Posterior parietal cortex lesions severely disrupt spatial learning in DBA mice
      characterized by a genetic hippocampal dysfunction.
AB  - C57BL/6 (C57) and DBA/2 (DBA) inbred mice with posterior parietal cortex or sham
      lesions were tested in a radial eight-arm maze task with all the paths baited. In
      the high learner C57 strain, parietal lesions produced a limited impairment of
      performance without affecting maze-running strategies while the same lesions were
      found to affect more severely performance in the poor learner DBA strain. Because
      (1) the processing of spatial information has been found to depend on the
      conjunctive participation of the hippocampus and the posterior parietal cortex,
      and (2) DBA mice represent a genetic model of hippocampal dysfunction, the fact
      that parietal lesions impair spatial performance more severely in the DBA strain
      suggests that the contribution of the posterior parietal cortex to spatial
      learning depends on the degree of functionality of the hippocampus.

PMID- 9754881
TI  - A new continuous alternation task in T-maze detects hippocampal dysfunction in
      mice. A strain comparison and lesion study.
AB  - The mammalian hippocampus has been the focus of several neurobiology studies
      because of its important behavioral function and because long-term potentiation
      (LTP) is a prominent feature of this brain region. Converging evidence suggests
      that hippocampal function is associated with learning multiple relationships of
      environmental cues. In this paper a novel behavioral test procedure is
      introduced, a modified T-maze continuous alternation task (T-CAT), that may serve
      as a simple, automatable, and quick test of hippocampal function in addition to
      the frequently applied water maze and fear conditioning paradigms. A comparison
      is made between mice (strain C57BL/6) with ibotenic acid lesioned or vehicle
      injected hippocampus, two transgenic strains (on CD1 background) overexpressing a
      calcium binding protein, S100beta, and inbred (C57BL/6, DBA/2, 129/SV and
      129/SVEV) and outbred (CD1) strains of mice. This study shows that hippocampal
      lesioning led to a significant impairment in T-CAT. Furthermore, overexpression
      of S100beta, which impairs hippocampal LTP, also led to an impairment
      demonstrating that T-CAT is sensitive to detect hippocampal dysfunction. Analysis
      of the mouse strains revealed that C57BL/6 and CD1 mice performed well in T-CAT,
      whereas 129/SV, 129/SVEV and DBA/2 were significantly impaired, a finding that
      underscores the importance of strain differences in pharmacological or single
      gene manipulation studies of hippocampal function in mice.

PMID- 9754882
TI  - D1 dopamine receptors and the reversal of isolation-induced behaviors in mice.
AB  - In a previous study, it was demonstrated that the high rates of social reactivity
      exhibited by isolated male mice in a dyadic encounter were mediated, at least in
      part, by an increased sensitivity of the D1 dopamine receptors. The present
      research was guided by the hypothesis that the behavioral effects of isolation
      are reversible, and that changes in dopaminergic function support this
      reversibility. To this end, mice selectively bred for high and low levels of
      aggression were reared in isolation from weaning (21 days) to puberty (45 days),
      at which point they were either assigned to groups or left in isolation until day
      69. By comparison to the continuous isolation condition, mice that eventually
      formed groups exhibited significantly less reactivity in a dyadic test conducted
      on day 69, showed a reduced response to dihydrexidine (DHX), and a decreased
      density of D1 dopamine receptors. This experiment provided evidence for the
      plasticity of the neurobiological system supporting reactive responses, and
      confirmed the view that its functional organization is open to experientially
      induced changes.

PMID- 9754883
TI  - Drug withdrawal convulsions and susceptibility to convulsants after short-term
      selective breeding for acute ethanol withdrawal.
AB  - High Alcohol Withdrawal (HAW) and Low Alcohol Withdrawal (LAW) mice were
      selectively bred from a foundation population of C57BL6/J (B6) x DBA/2J (D2) F2
      intercross progeny for display of intense or mild handling-induced withdrawal
      convulsions, respectively, following a single injection of a hypnotic dose of
      ethanol (alcohol; 4 g/kg). The HAW line had significantly greater alcohol
      withdrawal severity scores compared to the LAW line after only a single
      generation of selection; the magnitude of the line difference was 8-fold by the
      fourth selected generation. We tested these lines for severity of withdrawal
      convulsions following the benzodiazepine, diazepam; the gaseous anesthetic,
      nitrous oxide; the imidazopyridine, zolpidem and the barbiturate, pentobarbital.
      In all cases, HAW mice had significantly greater withdrawal severity than mice of
      the LAW line. These results indicate that some genes influencing withdrawal
      convulsion severity following ethanol also affect withdrawal from other CNS
      depressants. D2 mice are more sensitive to a variety of convulsants than B6 mice
      (and have more severe withdrawal convulsions). We, therefore, tested separate
      groups of mice of both selectively bred lines for threshold sensitivity to
      pentylenetetrazol (PTZ), N-methyl-D-aspartate (NMDA) and kainic acid (KA). No
      line differences were detected. These results indicate that genes influencing
      severity of withdrawal from several depressant drugs are largely different from
      those affecting susceptibility to GABAergic or glutamatergic convulsants.

PMID- 9754884
TI  - Non-selective attention and nitric oxide in putative animal models of Attention
      Deficit Hyperactivity Disorder.
AB  - Non-selective attention (NSA) to environmental stimuli has been measured in
      putative animal models of Attention-Deficit Hyperactivity Disorder (ADHD), such
      as the Spontaneously Hypertensive (SHR) and the Naples High-Excitability (NHE)
      rat lines. A series of experiments has been carried out on male juvenile SHR and
      Wistar-Kyoto (WKY) controls (experiment 1) and on the NHE and two controls, i.e.
      the Naples Low-Excitability (NLE) and a random-bred (NRB) line (experiment 2). It
      was done under basal conditions or following a single injection of the nitric
      oxide synthase (NOS) inhibitor L-nitro-arginine-methylester (L-NAME: 0.1-10
      mg/kg, i.p.), or vehicle, 30 min before testing on day 1 and vehicle alone before
      testing on days 2 and 3 in SHR/WKY (experiment 3) and the Naples lines
      (experiment 4). The behavior in a Lat maze during three consecutive 10-min
      exposures at 24-h intervals was monitored by a CCD video camera and analyzed off
      line for frequency and duration of rearings on hindlimbs per 1-min blocks. The
      results demonstrated that both SHR and NHE rats showed a higher frequency of
      rearings of shorter duration than controls. With time of testing, the duration of
      rearings tended to increase in the WKY but not the SHR. In the Naples lines the
      duration tended to increase in all but mostly in the NHE rats. The acute
      inhibition of NOS by L-NAME significantly increased the duration of rearing
      episodes both in SHR and NHE rats only at 10 mg/kg in the second part of the
      testing period. Therefore, NSA, as indexed by the duration of rearings, is
      defective in both hyperactivity models against different genetic backgrounds. In
      addition, this impairment is dependent upon nitric oxide (NO), which appears to
      play a significant role in these processes.

PMID- 9754885
TI  - Neuronal and behavioral differences between Mus musculus domesticus (C57BL/6JBy)
      and Mus musculus castaneus (CAST/Ei).
AB  - Previous studies have demonstrated that classical inbred strains of laboratory
      mice do not exhibit large genetic distances when simple sequence repeats (SSRs)
      are used to test for their polymorphisms whereas mice from wild origin exhibit
      high polymorphisms (more than 90%) for these sequence when compared with
      classical inbred strains of laboratory mice. The difference between Mus musculus
      castaneus and C57BL/6J reaches 98% and F1s male and female are fertile. These two
      properties pave the way for gene mapping derivating segregating generations
      between these strains. The phenotypical characteristics of Mus musculus castaneus
      have not been investigated, unfortunately. The first screening of Mus musculus
      castaneus and C57BL/6By was carried out for sensorial and motor development,
      spontaneous behavior in new environment, paw preference, maternal behavior,
      aggression in two different situations and time to learn escape in a water maze.
      Morphometry of hippocampus and weight of the male reproductive organs for
      measures that have been reported to be correlated with several of the examined
      behavior are also reported. The authors tested also reactivity to one drug (beta
      CCM) revealing seizure proneness. The two strains differ for 69% of the reported
      measures. Comparison to other strains for the same measures obtained in the
      laboratory for identical tests with mice reared in identical situations provided
      the mean to compare Mus musculus castaneus with a large set of more or less
      traditional mice. This strain has the most extreme position for 80% of the
      comparisons.

PMID- 9754886
TI  - The role of non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the
      therapy of HIV-1 infection.
AB  - Non-nucleoside reverse transcriptase inhibitors (NNRTIs) have, in addition to the
      nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors
      (PIs), gained a definitive place in the treatment of HIV-1 infections. Starting
      from the HEPT and TIBO derivatives, more than 30 structurally different classes
      of compounds have been identified as NNRTIs, that is compounds that are
      specifically inhibitory to HIV-1 replication and targeted at the HIV-1 reverse
      transcriptase (RT). Two NNRTIs (nevirapine and delavirdine) have been formally
      licensed for clinical use and several others are in preclinical or clinical
      development [thiocarboxanilide UC-781, HEPT derivative MKC-442, quinoxaline HBY
      097 and DMP 266 (efavirenz)]. The NNRTIs interact with a specific 'pocket' site
      of HIV-1 RT that is closely associated with, but distinct from, the NRTI binding
      site. NNRTIs are notorious for rapidly eliciting resistance due to mutations of
      the amino acids surrounding the NNRTI-binding site. However, the emergence of
      resistant HIV strains can be circumvented if the NNRTIs, alone or in combination,
      are used from the start at sufficiently high concentrations. In vitro, this
      procedure has proved to 'knock-out' virus replication and to prevent resistance
      from arising. In vivo, various triple-drug combinations of NNRTIs (nevirapine,
      delavirdine or efavirenz) with NRTIs (AZT, 3TC, ddI or d4T) and/or PIs (indinavir
      or nelfinavir) have been shown to afford a durable anti-HIV activity, as
      reflected by both a decrease in plasma HIV-1 RNA levels and increased CD4 T
      lymphocyte counts.

PMID- 9754887
TI  - Cartesian coordinate analysis of viral burden and CD4+ T-cell count in human
      immunodeficiency virus type-1 infection.
AB  - We have used a Cartesian coordinate plot to analyze the inverse relationship
      between viral burden (x-axis) and peripheral blood CD4+ cell count (y-axis) to
      extend our understanding of the mechanisms of antiviral drugs and differences in
      outcome resulting from variability in virus and host responses. Each of 186
      subjects studied were assigned to one of four response quadrants. Quadrants A (x
      , y+) and D (x+, y-) defined the effect of a change in virus load on the inverse
      change in CD4+ cell count expected from the natural history of HIV infection or
      antiretroviral therapy. Quadrants B (x+, y+) and C (x-, y-) defined the
      dissociation of the inverse relationship between the relative changes in CD4+
      cell count and viral load that resulted from the hypothesized effect of putative
      virologic or immunologic response modifiers. Of the response modifiers studied,
      only the syncytium-inducing phenotype resulted in a complete dissociation of this
      inverse relationship. The analysis provided an integrated virological and
      immunological approach to better understand therapeutic responses and potential
      dissociation between changes in viral RNA and CD4+ cell count. This type of
      analysis may be helpful for individualizing patient management as well as
      designing and analyzing studies of HIV-1 antiretroviral drugs and disease
      pathogenesis.

PMID- 9754888
TI  - Interferon-alpha inhibits the emergence of cellular stress response-dependent
      morbillivirus large plaque variants.
AB  - Cellular levels of heat shock proteins (HSPs) are elevated in response to
      physiologic states accompanying acute virus infection (e.g. fever). The objective
      of the present work was to define the antiviral effect of purified human
      lymphoblastoid IFN in the presence of HSP over-expression. For this purpose,
      canine distemper virus (CDV) was used since the response of CDV transcription and
      persistent infection phenotype to elevated HSP is characterized. First, the
      effect of elevated HSP on CDV lytic infection phenotype in Vero and CV1 cells was
      defined, and results extended to the closely related measles virus (MV). Cells
      expressing elevated levels of the major inducible 70-kDa HSP (hsp72) supported
      the emergence of large plaque variants of both CDV and MV from small plaque
      purified inocula. IFN treatment concurrent with infection caused a dosage
      dependent reduction in the expression of large plaque variants without affecting
      hsp72 levels or total plaque number. In contrast to the stress response-induced
      large plaque variant, small plaques were resistant to the antiviral effects of
      IFN. These data demonstrate the ability of IFN to selectively abrogate the pro
      viral effects of HSP over-expression, inhibiting the formation of a plaque
      phenotype that is correlated to enhanced virulence in animal models of
      morbillivirus encephalitis.

PMID- 9754889
TI  - The effect of increasing gastric pH upon the bioavailability of orally
      administered foscarnet.
AB  - For systemic use, the anti-cytomegalovirus (CMV) agent foscarnet must be given
      intravenously because oral administration results in unmeasurable or barely
      measurable plasma levels. At low pH, foscarnet decomposes via an acid-catalyzed
      decarboxylation; therefore, poor oral bioavailability might be due to
      decomposition of foscarnet in gastric acid. We evaluated whether increasing
      gastric pH with ranitidine would enhance the absorption of oral foscarnet in six
      asymptomatic HIV-infected individuals. Each volunteer received two oral 4000-mg
      (60 mg/kg) doses of foscarnet, preceded intravenously by a 20-min infusion of
      either ranitidine 50 mg in D5W or D5W alone in a randomized, double-blind, cross
      over study. Intragastric pH monitoring revealed that subjects had evidence of
      gastric acid production (pH < 2.0) prior to administration of ranitidine and
      increased gastric pH (pH > 6.0) following ranitidine administration. Most
      foscarnet plasma levels were below the assay limit of detection (33 microM) with
      only 4/30 levels detectable after D5W and 8/30 after ranitidine. Urinary recovery
      of foscarnet increased after ranitidine pretreatment. A mean recovery of 9.9% of
      the drug was realized in the urine in 24 h following ranitidine pretreatment
      compared to 6.2% of the dose after D5W pretreatment (P < 0.03). We estimate that
      9.9% recovery in the urine in 24 h is equivalent to absorption of 17.1% of the
      oral dose. In spite of the enhanced bioavailability associated with ranitidine
      pretreatment, the degree of absorption is still insufficient to achieve effective
      plasma concentrations for the treatment of CMV or acyclovir-resistant herpes
      viruses. We conclude that gastric acidity is a determinant of foscarnet
      absorption, albeit not a major one. Oral foscarnet is unlikely to be clinically
      useful even if administered in the setting of increased gastric pH.

PMID- 9754890
TI  - Long-term stability of the anti-influenza A compounds--amantadine and
      rimantadine.
AB  - Amantadine and rimantadine hydrochloride were tested for stability after storage
      at different temperatures and under different conditions for extended periods of
      time. Both compounds were quite stable after storage for at least 25 years at
      ambient temperature; they both retained full antiviral activity after long-term
      storage or after boiling and holding at 65-85 degrees C for several days. Thus,
      amantadine and rimantadine could be synthesized in large quantities and stored
      for at least one generation without loss of activity in preparation for the next
      influenza A pandemic in humans.

PMID- 9754891
TI  - Staged basilic vein transposition for dialysis angioaccess.
AB  - BACKGROUND: To find out a suitable procedure to dissect an arterialised thick
      walled vein to create secondary angioaccess for dialysis. Delicacy of the vein
      wall, high rate of thrombosis and difficulty to find out a suitable vein are the
      main obstacles to vascular surgeons during the creation of secondary angioaccess.
      METHODS: Forty patients in need for secondary angioaccess for dialysis were
      admitted for basilic vein transposition. They were classified randomly into two
      equal groups matched for age and sex. Group A patients were submitted to
      traditional basilic vein transposition. In group B, the operation was done in two
      stages. In the first stage, brachiobasilic anastomosis was done. Two to four
      weeks later the second stage was done to 19 patients (one patient had occluded
      shunt before the second stage) in the form of superficialization of the vein to
      be placed in the subcutaneous tissue. RESULTS: Follow-up period for 6-24 months
      revealed that in the early postoperative period (4 weeks after operation) patency
      rate was 12/20 (60%) in group A and 18/20 (90%) with significant difference
      (p<0.05) between the two groups. Later, occlusion occurred in two patients in
      each group. At the end of the study the overall patency was 10/20 (50%) and 16/20
      (80%) in group A and B respectively with significant difference between them.
      Both groups were similar in minor complications. CONCLUSIONS: The staged basilic
      vein transposition is superior to the traditional operation in the patency rate
      and is recommended as a safe operation for a successful secondary angioaccess.

PMID- 9754892
TI  - Clinical evaluation of new global clotting assay for monitoring of LMWH
      treatment: pilot study.
AB  - Until now, there has been no reliable method for the monitoring low molecular
      weight heparin (LMWH) therapy. Based on our observations of the coagulant
      activity of pseudoserum obtained after clotting of recalcified plasma from
      patients who were treated with LMWH, we were led to develop a new global clotting
      assay for the monitoring of this treatment. Methods description. After performing
      Howell time on PPP, samples were incubated for 30 min in 37 degrees C and they
      were then centrifuged for 10 min 0.2 ml of this pseudoserum is added to 0.2 ml of
      citrated normal plasma. Pseudoserum triggered coagulation of normal plasma and
      the time of new clot formation is expressed in seconds. This assay was called
      ATHU-test (AHEPA Thromb Haem Unit). We tested 21 normal subjects a in order to
      define the normal mean value and the range of the method. b) We also checked the
      reproducibility of the method by repeating the ATHU-test 17 times on the same
      normal plasma. c) We performed in vitro experiments to study its reliability and
      we added increasing concentrations using given doses of enoxaparine (4, 8, 12, 16
      mg/ml) or fraxiparine (1.5, 3.0, 4.5, 6 u aXa/ml) which was added in vitro to
      normal plasma confirming the proportional linear regression between duration of
      our test and the amount of LMWH. Finally d) we checked on the therapy response
      and the LMWH levels in blood for thrombophiliacs. Results. a) NP, n=21, X=138.6+/
      41.1, range 75-225 sec which means that values >X+/-3S=261.9 are distinctively
      pathological. b) The reproducibility of the method is acceptable, CV=9%. c) It is
      confirmed that in vitro addition of precautionary doses of LMWH (1.5 u aXa/ml)
      exceeds the coagulation time of ATHU-test up to 300 sec and it follows a
      distinctively proportional relationship. d) The monitoring of 20 thrombophiliacs
      for 2 months proved that: i) All their test times were between 4-15 min. The more
      we approach the value of 15 min the more danger there is of haemorrhage while, on
      the contrary, the more values approach 4 min the more the danger of rethrombosis
      increases. We present the ATHU-test, a simple test which has been used for 6
      months now by our Unit, in order to control the LMWH therapy for patients with
      thromboembolic diseases. The ATHU-test's reproducibility and its small range of
      normal values, the distinct relationship between therapeutic doses and
      therapeutic clinical results, as well as the in vitro proof of the linear
      regression between the coagulation time and the containing amount of LMWH, are
      likely to establish a new method of choice for the monitoring of LMWH therapy.

PMID- 9754893
TI  - Color duplex sonography guided stent placement in a stenosis of the superficial
      femoral artery. A case report.
AB  - We report the first case of a successful stent placement under color coded
      ultrasound guidance alone in the superficial femoral artery of a 73-year-old
      woman suffering from intermittent calf claudication following restenosis after an
      uncomplicated angioplasty five months previously. Because of a hemodynamically
      residual stenosis after three attempts at dilatation, a percutaneous transluminal
      angioplasty and stent insertion were performed under the sole guidance of color
      coded ultrasound. The intervention was performed without complication and at the
      six-month follow-up examination, the patient was symptom-free and the stent was
      morphologically intact and hemodynamically functional. This case shows that
      successful stent placement under ultrasonic guidance alone, without fluoroscopic
      control is possible, provided that there is adequate sonographic visualization.

PMID- 9754894
TI  - How "gold" is the standard? Interobservers' variation on venograms.
AB  - BACKGROUND: The aim of this study was to determine the degree of agreement
      between radiologists having different levels of experience, in reporting 151
      venograms independently. It was also aimed to assess whether the degree of
      disagreement would have influenced the final outcome of a thromboprophylactic
      study and the decision to anticoagulate the patients. METHODS: Seventy-eight
      patients undergoing total hip replacement had bilateral venography on
      postoperative days 8-12. Patients were allocated to receive either a low
      molecular weight heparin (enoxaparin) with or without TED stockings or a placebo
      Each of the 151 venograms obtained has been reported on four times. RESULTS: The
      overall incidence of deep venous thrombosis was 42% (33 of 78 patients). The
      range of the Kappa value of each radiologist versus the others was 0.568 to
      0.669. There was a significant decrease in the incidence of deep venous
      thrombosis in the treatment versus the placebo groups. On an intention to treat
      all diagnosed thrombi, a difference of up to 16% was demonstrated between the
      report of individual radiologists and the panel. This difference was reduced to
      8% when only thrombi proximal to the calf were considered clinically significant.
      CONCLUSIONS: These differences reflect the radiologist's experience and frequency
      of reporting on venograms and should be taken into account when studies for
      thromboprophylaxis are planned.

PMID- 9754895
TI  - Restricted usage of T-cell receptor Valpha-Vbeta genes in infiltrating cells in
      the aortic tissue of a patient with atherosclerotic aortic aneurysm.
AB  - We report a rare case of an atherosclerotic aortic aneurysm with lymphocyte
      infiltration in which T-cell receptor (TCR) Valpha as well as Vbeta gene usage
      was restricted. Immunohistochemical studies showed that the infiltrating cells
      mainly consisted of macrophages, natural killer (NK) cells, cytotoxic T
      lymphocytes (CTLs) and T-helper (Th) cells, and that there were almost no
      infiltrating delta T lymphocytes, and human leukocyte antigen (HLA) class I and
      65-kD heat-shock protein (HSP-65) was not strongly expressed in the aortic
      tissue. Although the immunohistochemical data were consistent with an ordinary
      atherosclerotic aortic aneurysm, in which TCR Valpha-Vbeta gene usage is known to
      be polyclonal, the restricted TCR gene usage suggests that a certain autoimmune
      mechanism was involved in the pathogenesis of this case similar to Takayasu's
      arteritis, in which massive infiltration of delta T lymphocytes and strong
      expression of HSP-65 in the aortic tissue are characteristic.

PMID- 9754896
TI  - Prevention of deep vein thrombosis in knee arthroplasty. Preliminary results from
      a randomized controlled study of low molecular weight heparin vs foot pump
      compression.
AB  - BACKGROUND: We evaluated in a randomized controlled study the possibility to use
      foot pump mechanical compression compared to routine LMWH as prophylaxis against
      deep vein thrombosis during knee arthroplasty. METHODS: Forty patients were
      included in this preliminary report. Eleven patients withdrew, usually during the
      early phase of the study. RESULTS: Among the 29 patients completing a venography,
      27% in the compression group and none in the LMWH group had a DVT. This
      difference was statistically significant (p<0.05). One further patient in the
      compression group died from pulmonary embolism 17 days postoperatively.
      CONCLUSIONS: With the present study protocol, mechanical foot pump compression
      failed to be as efficient as LMWH prophylaxis.

PMID- 9754897
TI  - Plasma endothelin-1 concentrations in non-insulin-dependent diabetes mellitus and
      nondiabetic patients with chronic arterial obstructive disease of the lower
      limbs.
AB  - BACKGROUND: Endothelin-1 (ET-1), a vasoconstrictor and mitogenic endothelium
      derived peptide, has been considered as a marker for endothelial damage and
      potential contributor to the development of the atherogenic process. METHODS: To
      evaluate the pattern of plasma ET-1 secretion in non-insulin-dependent diabetes
      mellitus (NIDDM) and nondiabetic patients with chronic arterial obstructive
      disease (CAOD) of the lower limbs, plasma levels of ET-1 were determined in 12
      NIDDM patients (10 men and 2 women; mean age 63+/-8 years) with CAOD of the lower
      limbs at Fontaine stage II and in 12 nondiabetic patients (11 men and 1 woman;
      mean age 62+/-4 years) with comparable arteriopathy. Ten normal subjects
      comprised the control population. RESULTS: The plasma levels of ET-1 in NIDDM
      patients with CAOD of the lower limbs were 5.7+/-0.3 pmol/L, which represented a
      significant (p<0.001) difference from the values in nondiabetic patients with
      comparable arteriopathy (4.1+/-0.6 pmol/L) and those in the control group (2.7+/
      0.7 pmol/L). Plasma levels of ET-1 showed a significant (p<0.0001) positive
      correlation with the levels of fasting insulin in NIDDM patients with CAOD of the
      lower limbs. Increased plasma ET-1 could reflect a major and/or more diffuse
      endothelial cell damage or dysfunction in NIDDM than in nondiabetic patients with
      comparable CAOD of the lower limbs. Augmented mitogenic ET-1 levels could also
      have a role both in diabetic and nondiabetic angiopathy. CONCLUSIONS: The
      positive correlation between ET-1 plasma levels and fasting insulin levels in
      NIDDM patients with CAOD of the lower limbs suggests that the increased ET-1
      release could be related to the augmented insulin secretion in these patients.
      Insulin-related overproduction of ET-1 could promote the atherogenic process and
      enhance the vascular tone to a greater extent in NIDDM than in nondiabetic
      patients with CAOD of the lower limbs.

PMID- 9754898
TI  - Duplex sonography of vascularization of venous thrombosis.
AB  - BACKGROUND: Changes in the echogenicity of an ageing intravenous thrombus have
      already been described in B-mode sonography. We tried to investigate the
      phenomena of vascularisation of the intravenous thrombotic material during the
      organisation using colour Doppler sonography. METHODS: We carried out a
      prospective investigation of 8 jugular vein, 6 femoral vein and 1 inferior caval
      vein thrombosis. The thromboses were investigated with a colour Doppler
      sonographic device from Siemens, type Elegra, every second or third day for 4
      weeks after making the diagnosis. We looked for intrathrombotic colour Doppler
      signals with an arterial pulsatile blood flow in the pulsed Doppler mode.
      RESULTS: We found arterial signals in the intravenous thrombus in 8 of the 15
      patients. Such arterial Doppler signals were supposed to be arterial vessels
      which develop during the organisation of the thrombotic material. The arterial
      vessels appeared only in a short range of time from the 11th to the 25th day and
      were present in circumscribed areas of the thrombus. Arterial blood vessels in
      the surrounding tissue of the veins which may supply blood to the intrathrombotic
      vessels could not be demonstrated. CONCLUSIONS: Thus the intravenous
      documentation of arterial vessels in an organising intravenous thrombus is
      possible. This may give information about the mechanism of thrombogenesis and
      about the degree of organisation and may also help in determining the age of the
      thrombosis.

PMID- 9754899
TI  - Venous ulcers in chronic venous insufficiency: King Khalid University Hospital
      experience.
AB  - BACKGROUND: The purpose of this study was to identify the anatomical location of
      the venous disease in C.V.I. patients presented with venous ulcers in addition to
      discussing the management. DESIGN: Retrospective study, at King Khalid University
      Hospital. METHODS: Between January 1991 to January 1997, 90 patients (63 females,
      27 males) with CVI were evaluated. The evaluation included history, clinical
      examination, bidirectional ultrasound continuous wave Doppler, Duplex, ambulatory
      venous pressure (AVP), ascending and descending venography. RESULTS: Forty eight
      (48) patients (57 limbs) had Stage III with venous ulcers. Out of these 48
      patients, fifteen (15) showed deep venous system involvement with deep vein
      thrombosis (DVT). Thirty three (33) patients had venous reflux in the superficial
      or deep systems without occlusion. Out of these 33 patients, 24 patients had
      superficial system reflux, while the remaining 9 patients revealed deep system
      reflux with a competent superficial system. CONCLUSIONS: Superficial venous
      incompetence plays a major role in venous ulcer formation and that location and
      type of venous disease should be thoroughly investigated as surgical excision of
      the superficial system leads to a long standing recurrence free period.

PMID- 9754900
TI  - Aneurysm induced by periarterial application of elastase heals spontaneously.
AB  - BACKGROUND: The pathogenesis of aortic aneurysms remains largely unknown, despite
      aneurysmal rupture being an increasingly common catastrophe. METHODS: This study
      was designed to elucidate the mechanism of arterial dilatation histologically and
      electron microscopically, utilising a new animal model. Elastase, 3.0 mg/ml, was
      applied to the abdominal aortae of 18 New Zealand white rabbits from the
      adventitia side for 3 hours. The rabbits were sacrificed at 0, 3, 14, 28, 42 and
      90 days after the procedure (n=4, 3, 2, 2, 2, 3). RESULTS: Two rabbits were found
      to have developed aortic rupture. On day 0, elastase application induced fusiform
      aneurysms up to 1.62+/-0.14 times the pre-elastase application aortic diameter.
      Dilated walls revealed medial elastolysis, degeneration of smooth muscle cells
      (SMCs) and damaged endothelial cells. By day 3, the smooth muscle cells had
      changed to the synthetic type. Aneurysms did not progress, and after 42 days,
      showed gradual shrinkage. By day 90, aortic diameters had nearly normalised.
      CONCLUSIONS: Aortic walls also returned to the pre-elastase application thickness
      and some mature medial elastic lamellae showed regeneration. Medial smooth muscle
      cells reverted to the contractile type. Aortic dilatation induced by peri-aortic
      application of elastase heals spontaneously, accompanied by regeneration of
      smooth muscle cells. Irreversible degeneration of medial smooth muscle cells
      appears to be more critical to aneurysm formation than degeneration of elastic
      lamellae.

PMID- 9754901
TI  - The white blood cell and plasma fibrinogen in thrombotic stroke. A significant
      correlation.
AB  - OBJECTIVES: Thrombotic stroke is a common disorder with considerable mortality
      and morbidity. Risk factors for stroke include cigarette smoking, hypertension
      and hyperlipidaemia and these have been linked to abnormalities of haemorrheology
      and coagulation such as increased fibrinogen. Other haemorrheological
      abnormalities have also been documented. These include an elevation in the white
      blood cell (WBC) count. The aim of our study was to evaluate plasma fibrinogen,
      WBC aggregation and the release of free radicals in thrombotic stroke.
      EXPERIMENTAL DESIGN: Thirty-four patients with thrombotic stroke were enrolled in
      the study. The data were compared to 58 matched controls. SETTING: This study was
      carried out in Ninewells Hospital, Dundee on patients previously admitted to the
      medical wards with acute stroke. MEASURES: Plasma fibrinogen, WBC aggregation and
      plasma malondialdehyde (MDA) were measured in this study. RESULTS: As expected,
      the stroke patients have a significantly higher fibrinogen level (4.3+/-1.2 g/dl
      versus 3.1+/-0.6, p<0.001). WBC aggregation is also increased in the patient
      group (47.5+/-10.4% versus 42.7+/-10.6, p=0.036), as is plasma MDA (8.6+/-2.0
      micromol/l versus 7.1+/-1.07, p<0.001). The factor VIII von Willebrand factor
      antigen measured as a marker as vascular damage was also significantly higher in
      the patient group (251+/-87% versus 182+/-64, p<0.001). There was also a
      statistically significant correlation between fibrinogen level and WBC
      aggregation, and fibrinogen and MDA. These are both statistically significant
      p=0.012 and p<0.001 respectively. CONCLUSIONS: We believe our study suggests that
      enhanced WBC aggregation/adhesion with release of free radicals may be another
      mechanism whereby fibrinogen exerts its known detrimental effect in stroke
      development. This may allow planning of therapeutic strategies as yet
      undeveloped.

PMID- 9754902
TI  - Surgical treatment of spontaneous internal carotid dissection.
AB  - Spontaneous dissection of the internal carotid artery is rarely submitted to
      surgery. We report a case successfully operated on with complete restoration of
      the cerebral blood flow. A 43-year-old male was admitted to our hospital 10 days
      after an episode of amaurosis fugax of the left eye, left sided headache and
      paresis of the right arm of a few hours duration. A diagnosis of dissection of
      the left internal carotid artery was made by duplex and triplex ultrasound
      examination and was confirmed by cerebral arteriography in contrast to magnetic
      resonance angiography which was misleading. Due to the slow arterial flow from
      the right to the left cerebral hemisphere through only the posterior
      communicating arteries we envisaged the possibility of a cerebral infarction if
      the dissection were to be extended. For this reason a surgical procedure was
      performed by excising the dissected segment and inserting a venous graft for the
      re-establishment of the arterial flow. Surgical treatment of spontaneous internal
      carotid dissection should be considered very carefully when the clinical and
      laboratory findings suggest the possibility of an impending stroke.

PMID- 9754903
TI  - Microglial and astrocytic involvement in a murine model of Parkinson's disease
      induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
AB  - We have studied the reaction of glial cells in mice treated with an
      intraperitoneal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP), a selective neurotoxin of dopaminergic nigrostriatal neurons. Signs of
      injury to the dopaminergic neurons started on the 1st day after MPTP
      administration and progressed up to the end of the observation time (21st day). A
      transient microglial reaction was demonstrated from the 1st until the 14th day in
      the substantia nigra (SN) and striatum. The cells showed an increase in number
      and changes in morphology. At the ultrastructural level, signs of phagocytosis
      and features indicating the secretion of biologically active substances were
      observed. Astrocytosis followed the microglial reaction by one day and was
      noticed until the end of the observation time. Interleukin-6 immunoreactivity was
      observed within microglia and astrocytes in the SN on days 2 and 3. There were no
      signs of depletion of dopaminergic cells or glial activation after the
      administration of MPTP simultaneously with pargyline, an inhibitor of monoamine
      oxidase-B that prevents MPTP neurotoxicity. Our study indicates that microglia
      and astrocytes are involved in the pathological process in the nigrostriatal
      system following MPTP administration. MPTP alone is not responsible for glial
      cell activation but its metabolite MPP+ and/or agents released by injured neurons
      may participate in this process.

PMID- 9754904
TI  - The inhibitory effect of ursodeoxycholic acid and pentoxifylline on platelet
      derived growth factor-stimulated proliferation is distinct from an effect by
      cyclic AMP.
AB  - This study assessed the ability of ursodeoxycholic acid (UDCA) and one of its
      metabolites, tauroursodeoxycholic acid (TUDCA), to inhibit platelet derived
      growth factor (PDGF) stimulated fibroproliferation and compared these results to
      the effect of pentoxifylline and its metabolite-1 [1-(5-hydroxyhexyl)-3,7
      dimethylxanthine] and assessed the potential role of cyclic AMP in this process.
      Fibroproliferative activity was measured by the tritiated thymidine uptake assay
      in human fibroblast cultures. All four compounds: pentoxifylline, metabolite-1,
      UDCA and TUDCA inhibited the fibroproliferative activity stimulated by PDGF (8
      ng/ml). Incubation of fibroblasts with dibutyryl cyclic AMP reduced proliferation
      stimulated by PDGF suggesting that the PDGF stimulated proliferation was
      sensitive to inhibition by a membrane permeable analogue of cyclic AMP.
      Incubation of myofibroblasts with dibutyryl cyclic AMP significantly inhibited
      PDGF stimulated proliferation suggesting that cyclic AMP can regulate PDGF
      stimulated proliferation in the myofibroblast. To determine if the effect of
      pentoxifylline on fibroproliferation was mediated by cyclic AMP, we used
      dideoxyadenosine, a potent inhibitor of adenylyl cyclase. The effect of
      pentoxifylline on fibroproliferation was not prevented by dideoxyadenosine, which
      inhibits formation of cyclic AMP, thus suggesting that the inhibitory effect of
      pentoxifylline on PDGF-stimulated proliferation of fibroblasts was not mediated
      by cyclic AMP, arguing against a role for cyclic AMP in this process.
      Combinations of UDCA (250 microM) plus pentoxifylline (120 microM) or UDCA (250
      microM) plus TUDCA (250 microM) inhibited fibroproliferative activity stimulated
      by PDGF to a greater extent than either drug alone. As UDCA has been reported to
      decrease cyclic AMP these results argue against a role for cyclic AMP in this
      process. Finally the results suggest that UDCA may inhibit PDGF-stimulated
      proliferation via an inhibition of C-kinase.

PMID- 9754905
TI  - The effect of fluticasone propionate on respiratory syncytial virus-induced
      chemokine release by a human bronchial epithelial cell line.
AB  - Respiratory syncytial virus (RSV) is an important cause of bronchiolitis in
      infants, is an important trigger of asthma exacerbation, and stimulates chemokine
      production by human respiratory epithelial cells in vitro. We tested the effect
      of the corticosteroid fluticasone propionate (FP) on RSV-stimulated production of
      the chemokines interleukin 8 (IL-8) and RANTES (regulated upon activation, normal
      T cell expressed and secreted) by a human bronchial epithelial cell line, BEAS
      2B. Confluent BEAS-2B cultures were inoculated with RSV at approximately 1 plaque
      forming unit/cell, and media were collected at 24 h intervals. Concentrations of
      IL-8 and RANTES were measured in supernatants using ELISA. The effect of FP at
      varying concentrations on RSV-induced chemokine release was determined. RSV
      stimulated increased release of both IL-8 and RANTES, particularly at 24-48 h
      after virus inoculation. Significant but incomplete inhibition of RSV-stimulated
      increases for both chemokines was found when cultures were treated with FP at >
      or = 10(-8) M (for IL-8) or > or = 10(-7) M (for RANTES). There was no
      significant effect of FP on release of RSV itself from infected BEAS-2B cells. We
      conclude that a possible mechanism for the efficacy of inhaled corticosteroids in
      reducing the frequency or severity of asthma exacerbations is inhibition of virus
      induced chemokine production by airway cells.

PMID- 9754906
TI  - Effects of 2-deoxy-D-glucose administration on immune parameters in mice.
AB  - Physical exercise and diet alterations have been shown to affect immune
      parameters. Similar effects are also induced by the administration of the non
      metabolizable glucose analog, 2-deoxy-D-glucose (2-DG). The current study was
      designed to characterize the effects of glucoprivation induced by 2-DG
      administration on leukocyte subset distribution and function. BDF1 mice (n = 8
      per group) were injected intraperitoneally one or three times with 0, 500, 750,
      1000 or 1500 mg/kg of 2-DG. Two hours after the last injection of 2-DG,
      immunological parameters were analyzed. A dose-dependent increase in plasma
      glucose concentrations of mice injected once with up to 1500 mg/kg of 2-DG was
      observed (p < 0.001). After either one or three injections of up to 1500 mg/kg of
      2-DG, corticosterone levels, leukocyte counts in the spleen, and CD3+ cells in
      the thymus increased. In vitro proliferation of partially purified lymphocytes
      from the spleen in the presence of both concanavalin-A and lipopolysaccharide
      decreased in a dose dependent manner (p < 0.05). In addition, after three
      injections, the proportion of both thymocytes and splenocytes bearing alphabeta
      TCR increased as the concentration of 2-DG increased (p < 0.01). These results
      demonstrate that 2-DG administration induced dose-dependent changes in both
      thymus and spleen cell distribution and function.

PMID- 9754907
TI  - Effect of a traditional Chinese medicine, Bu-zhong-yi-qi-tang on the protection
      against an oral infection with Listeria monocytogenes.
AB  - The protective effect against an oral infection with Listeria monocytogenes was
      observed in BALB/c mice who were orally administered a traditional Chinese
      medicine, Bu-zhong-yi-qi-tang (Japanese name: Hochu-ekki-to, HOT) daily for 7
      days. Bacterial numbers in the Peyer's patch (PP) at 18 h, in the mesenteric
      lymph nodes (MLN) at 18 h, 1 day and 3 days and in the liver at 3 days after
      infection were significantly suppressed in HOT-treated mice, although there was
      no difference in the bacterial number in the small intestinal contents. The
      enhanced bactericidal activities of PP and liver macrophages by pretreatments of
      HOT were observed. The protective effect of HOT was not observed in athymic nu/nu
      and IFN-gamma deficient mice. The administration of HOT increased IFN-gamma
      producing cells in the intestinal intraepithelial lymphocytes (IEL) but did not
      in the PP, MLN and liver. HOT exerts effects mainly on CD8alphabeta+ IEL which
      are thymus-dependent, and induced IFN-gamma production from their cells. These
      results suggest that HOT acts on the gut-associated lymphoid tissues and induces
      IFN-gamma from CD8alphabeta+ IEL, which activates PP and liver macrophages and
      consequently the resistance to L. monocytogenes is augmented in the mice.

PMID- 9754908
TI  - Modulation of serum histamine releasing activity in chronic idiopathic urticaria.
AB  - BACKGROUND: Sera of about 30% of patients with chronic idiopathic urticaria (CIU)
      have increased histamine releasing activity (HRA+) on normal basophils. It is not
      known whether other CIU sera would be HRA+ if a more sensitive histamine release
      assay was used. Although most HRA+ CIU sera appear to have anti Fc(epsilon)R1
      activity, it is not known whether post-binding basophil intracellular events are
      similar to those after anti-IgE stimulation. RESULTS: In the presence of D2O, the
      HR stimulated by 28 previously documented HRA- sera increased from 4+/-0.4 to
      21+/-4% with 13 of the 28 sera now considered HRA+. No previous HRA sera was HRA+
      with IL-3 treated cells. Histamine release induced by both HRA+ sera and anti-IgE
      were inhibited by genistein, and Ca2+/Mg2+ depletion but not by
      bisindoylmaleimide. HRA+ sera induced prominent HR from normal basophils with
      little surface IgE, but induced no increased HR from basophils unresponsive to
      anti-IgE. CONCLUSIONS: Up to 61% of CIU sera will induce increased HR from normal
      basophils in a sufficiently sensitive assay system. HR induced by most HRA+ sera
      is more prominent in basophils with very little surface IgE. However, there may
      be similar post-binding intracellular activation pathways following stimulation
      by HRA+ sera and anti-IgE.

PMID- 9754909
TI  - Different bronchial responsiveness to Ach between normal and OA-sensitized guinea
      pigs after acoustic stress: a role for adenosine.
AB  - Noise-exposure makes non-sensitized guinea pigs hyporesponsive to Acetylcholine
      (Ach), while in Ovalbumin (OA)-sensitized guinea pigs the responsiveness to the
      cholinergic mediator is not modified by acoustic stress (Nieri et al., 1996). The
      occurrence of bronchial hyporesponsiveness after acoustic stress in non
      sensitized guinea pigs was verified also with histamine, obtaining a result
      similar to that observed with Ach. Moreover, the role of adenosine as modulator
      of the bronchial responsiveness to Ach after noise-exposure was assessed both in
      normal and in sensitized guinea pigs. In non-sensitized noise-exposed guinea
      pigs, the hyporesponsiveness to Ach was abolished by pretreatment of the animals
      with the peripheral A1/A2 antagonist 8-p-(sulfophenyl)theophylline (8-pSPT, 3
      mg/kg i.v.) or with the A2-selective blocker 3,7-dimethyl-1-propargylxanthine
      (DMPX, 80 microg/kg i.v.) but not with the A1-selective antagonist Xanthine Amine
      Congener (XAC, 0.1 mg/kg i.v.). In sensitized guinea pigs, pretreatment with
      theophylline (25 mg/kg i.v.) makes noise-exposed animals again hyporesponsive to
      Ach, while no effect was obtained with the selective A1 and A2 antagonists
      employed. Also enprofylline (10 mg/kg i.v.), a phosphodiesterase inhibitor more
      potent than theophylline, does not modify the responsiveness to Ach in sensitized
      noise-exposed guinea pigs. The overall data presented suggest the involvement of
      the peripheral purinergic system in the regulation of airway reactivity after the
      stressful condition and indicate an altered functionality of this system as a
      consequence of sensitization. Furthermore, noise-exposure makes it possible to
      reveal in guinea pigs an opposite influence by theophylline on airway
      responsiveness to Ach, in sensitized, with respect to normal, animals.

PMID- 9754910
TI  - Induction of human B2 bradykinin receptor mRNA and membrane receptors by
      IFNgamma.
AB  - A potential mechanism for the increased sensitivity of inflamed tissues to
      bradykinin is the upregulation of bradykinin receptor expression. We report that
      recombinant human IFNgamma stimulated a concentration-dependent increase in cell
      surface bradykinin receptor expression in intact T24 human epithelial-like cells,
      determined by radioligand binding analysis. Analysis of specific [3H]-bradykinin
      binding revealed that IFNgamma-treated cells had a two- to threefold increase in
      bradykinin receptor number compared to the controls with no effect on receptor
      affinity. The ability of IFNgamma to stimulate increased bradykinin receptor
      expression was abrogated by treatment with either the transcription inhibitor
      actinomycin D or the protein synthesis inhibitor cycloheximide. IFNgamma enhanced
      steady-state human B2 bradykinin receptor mRNA expression in the T24 cells in a
      dose-dependent manner. B2 bradykinin receptor mRNA expression was increased as
      early as 1 h following IFNgamma stimulation, and continued to accumulate for 24
      h. Bradykinin-stimulated intracellular calcium mobilization was also increased in
      IFNgamma-treated T24 cells compared to controls. The ability of IFNgamma to
      upregulate B2 bradykinin receptors in primary epithelial cells was demonstrated
      using cultured human airway epithelial cells. These observations suggest that
      increasing IFNgamma levels during inflammation may upregulate the expression of
      B2 bradykinin receptors, leading to increased sensitivity to bradykinin.

PMID- 9754911
TI  - Vascular leak syndrome: a troublesome side effect of immunotherapy,
      Immunopharmacology, 39/3 (1998) 255.

PMID- 9754912
TI  - Anxiolytic-like action of neurokinin substance P administered systemically or
      into the nucleus basalis magnocellularis region.
AB  - There is evidence that the neurokinin substance P plays a role in neural
      mechanisms governing learning and reinforcement. Reinforcing and memory-promoting
      effects of substance P were found after it was injected into several parts of the
      brain and intraperitoneally. With regard to the close link between anxiety and
      memory processes for negative reinforcement learning, the aim of the present
      study was to gauge the effect of substance P on anxiety-related behaviors in the
      rat elevated plus-maze and social interaction test. Substance P was tested at
      injection sites where the neurokinin has been shown to promote learning and to
      serve as a reinforcer, namely in the periphery (after i.p. administration) and
      after injection into the nucleus basalis magnocellularis region. When
      administered i.p., substance P had a biphasic dose-response effect on behavior in
      the plus-maze with an anxiolytic-like action at 50 microg/kg and an anxiogenic
      like one at 500 microg/kg. After unilateral microinjection into the nucleus
      basalis magnocellularis region, substance P (1 ng) was found to exert anxiolytic
      like effects, because substance P-treated rats spent more time on the open arms
      of the plus-maze and showed an increase in time spent in social interaction.
      Furthermore, the anxiolytic effects of intrabasalis substance P were sequence
      specific since injection of a compound with the inverse amino acid sequence of
      substance P (0.1 to 100 ng) did not influence anxiety parameters. These results
      show that substance P has anxiolytic-like properties in addition to its known
      promnestic and reinforcing effects, supporting the hypothesis of a close
      relationship between anxiety, memory and reinforcement processes.

PMID- 9754913
TI  - Ethanol-reinforced behaviour in the rat: effects of uncompetitive NMDA receptor
      antagonist, memantine.
AB  - Ethanol has been reported to alter NMDA receptor-mediated biochemical and
      electrophysiological responses in vitro. The aim of the present study was to
      evaluate the effects of an uncompetitive NMDA receptor antagonist memantine, in
      animal models of alcoholism. Male Wistar rats were trained to drink 8% ethanol in
      a free-choice, limited access procedure. A separate group of animals was trained
      to lever press for 8% ethanol in an operant procedure where ethanol was
      introduced in the presence of sucrose. The selectivity of memantine's actions was
      assessed by studying its effects on food or water consumption in separate control
      experiments. Memantine (4.5-24 mg/kg) significantly, but not dose dependently,
      affected ethanol drinking in the limited access procedure. However, only 6 mg/kg
      memantine selectively decreased ethanol drinking. Memantine did not alter ethanol
      intake in rats trained to lever press for ethanol in the operant procedure. Only
      9 mg/kg memantine reduced operant responding in the extinction procedure in the
      rats trained to lever press for ethanol. The same dose of memantine significantly
      reduced the operant behaviour of rats trained to respond for water. These results
      indicate that: (i) single doses of memantine only moderately and not dose
      dependently reduce alcohol drinking in the limited access procedure; (ii)
      memantine produces non-selective effects on operant behaviour in rats trained to
      lever press for ethanol in an oral self-administration procedure.

PMID- 9754914
TI  - Autoradiographic study of [3H]flunitrazepam binding sites in the subnuclei of the
      thalamus of rats rendered tolerant to and dependent on pentobarbital.
AB  - We examined changes in benzodiazepine binding sites labeled by [3H]flunitrazepam
      in five nuclei of the thalamus, the central medial, central lateral,
      intermediodorsal, ventroposterior, and laterodorsal nuclei, in rats made tolerant
      to and dependent on pentobarbital. Animals were made tolerant by
      intracerebroventricular infusion with pentobarbital (300 microg (10 microl)(-1)
      h(-1) for six days) through pre-implanted cannulae. Pentobarbital dependence was
      assessed 24 h after abrupt withdrawal from pentobarbital. Pentobarbital-tolerant
      rats showed no significant change in [3H]flunitrazepam binding sites (Bmax and
      Kd) in any nucleus examined in the thalamus. In the rats made dependent on
      pentobarbital, significant increases in the Bmax of [3H]flunitrazepam binding
      without changes in Kd were noted in central medial and central lateral nuclei.
      GABAergic (gamma-aminobutyric acid) neurons in the ventrobasal nucleus and in
      nuclei in the midline group are important in seizure regulation and arousal.
      These findings suggest that alterations of benzodiazepine receptors in certain
      nuclei of thalami are involved in the physiological changes induced by
      pentobarbital dependence. There were no changes in the binding parameters for
      [3H]flunitrazepam in pentobarbital-tolerant rats.

PMID- 9754915
TI  - Alterations in [3H]L-N(G)-nitroarginine binding in brain after transient global
      or transient focal ischemia in gerbils and rats.
AB  - We investigated the post-ischemic change in [3H]L-N(G)-nitroarginine binding as a
      marker of nitric oxide (NO) synthase in the animal brain after transient global
      ischemia or transient focal ischemia. Transient global ischemia in gerbils was
      induced for 10 min followed by 1 h to 7 days of recirculation. Transient focal
      ischemia in rats was induced for 45 min followed by 3 days of recirculation.
      Following transient global ischemia, [3H]L-N(G)-nitroarginine binding showed a
      significant increase in the striatum (17-18%) and hippocampal CA1 sector (24%) at
      48 and 24 h after recirculation, respectively. The hippocampal CA3 sector also
      showed a significant elevation (32-40%) in [3H]L-N(G)-nitroarginine binding at 24
      and 48 h after global ischemia. Furthermore, the dentate gyrus showed a
      significant increase (30-32%) in [3H]L-N(G)-nitroarginine binding at 5, 24 and 48
      h after global ischemia. Thereafter, a significant reduction in [3H]L-N(G)
      nitroarginine binding was observed only in the dentate gyrus 7 days after
      recirculation. In contrast, [3H]L-N(G)-nitroarginine binding was unchanged in the
      thalamus throughout the recirculation periods. Histological analysis revealed
      that transient global ischemia caused severe damage or cellular damage in the
      striatum and the hippocampal CA1 sector. The hippocampal CA3 sector and thalamus
      were mildly damaged, whereas the dentate gyrus was morphologically intact.
      Following transient focal ischemia, a marked elevation (50-52%) in [3H]L-N(G)
      nitroarginine binding was found in the regions of the ipsilateral striatum in
      which severe infarction occurred. Our findings suggest that [3H]L-N(G)
      nitroarginine binding increases in the striatum and hippocampus after transient
      global ischemia or transient focal ischemia. This increase in [3H]L-N(G)
      nitroarginine binding may play a pivotal role not only in the pathogenesis of
      ischemic brain damage, but also in the restoration of injury areas after cerebral
      ischemia.

PMID- 9754916
TI  - Protective effect of N-(3-(aminomethyl)benzyl) acetamidine, an inducible nitric
      oxide synthase inhibitor, in brain slices exposed to oxygen-glucose deprivation.
AB  - It has been suggested that large amounts of nitric oxide (NO) produced by
      inducible NO synthase are involved in the mechanisms of neurotoxicity after
      cerebral ischaemia. We have recently demonstrated that inducible NO synthase was
      expressed within hours after rat forebrain slices were exposed to oxygen-glucose
      deprivation. Therefore, we sought to determine whether NO produced by inducible
      NO synthase contributes to tissue damage in this model, by using a new, highly
      selective, inhibitor of inducible NO synthase, N-(3
      (aminomethyl)benzyl)acetamidine (1400W). We found that incubation with 1400W from
      the start of the oxygen-glucose deprivation period until the end of the
      experiment decreases tissue damage determined as lactate dehydrogenase (LDH)
      efflux 4 h after the oxygen-glucose deprivation period, the time at which
      inducible NO synthase expression is maximal in this model. This effect may be a
      result of direct inhibition of inducible NO synthase activity, raising the
      possibility of a clinical use of selective inhibitors of this NO synthase isoform
      in the management of cerebral ischaemia.

PMID- 9754917
TI  - Biochemical, cellular and pharmacological activities of a human neuropeptide FF
      related peptide.
AB  - We report on the biochemical, cellular and pharmacological activities of SQA
      neuropeptide FF (Ser-Gln-Ala-Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2), a peptide
      sequence contained in the human neuropeptide FF (neuropeptide FF, Phe-Leu-Phe-Gln
      Pro-Gln-Arg-Phe-NH2) precursor. Quantitative autoradiography revealed that, in
      the superficial layers of the rat spinal cord, SQA-neuropeptide FF displayed the
      same high affinity for [125I]1DMe ([125I]D-Tyr-Leu-(NMe)Phe-Gln-Pro-Gln-Arg-Phe
      NH2) binding sites (Ki = 0.33 nM) as did neuropeptide FF (Ki = 0.38 nM). In
      acutely dissociated mouse dorsal root ganglion neurones, SQA-neuropeptide FF
      reduced by 40% the depolarisation-induced rise in intracellular Ca2+ as measured
      with the Ca2+ indicator, Fluo-3. In mice, 1DMe and SQA-neuropeptide FF dose
      dependently inhibited the antinociceptive effect of intracerebroventricular
      (i.c.v.) injections of morphine, but SQA-neuropeptide FF was less potent than
      1DMe. Furthermore, SQA-neuropeptide FF, as well as 1DMe, produced marked
      hypothermia following third ventricle injections in mice. These data demonstrate
      that the human peptide, SQA-neuropeptide FF, exhibits biochemical and
      pharmacological properties similar to those of neuropeptide FF or neuropeptide FF
      analogues, and belongs to the neuropeptide FF family.

PMID- 9754918
TI  - Interspecies differences in thromboxane A2 receptors are distinguished by
      glibenclamide.
AB  - The ability of the thromboxane A2 receptor antagonist, GR32191 ([1R
      [1alpha(Z),2beta3beta,5alpha]]-7-[5-[[(1,1'-biphe nyl)-4-yl]methoxy]-3-hydroxy-2
      (1-piperidinyl)cyclopentyl]-4-heptenoic acid), and the sulphonylurea,
      glibenclamide, to antagonise contractions to the thromboxane A2 mimetic, U46619
      ((15S)-hydroxy-11alpha,9alpha(epoxymethano)prosta-5Z, 13E-dienoic acid), were
      assessed in rat and guinea-pig isolated large (aorta) and small (mesentery and
      coronary) arteries. U46619 concentration-response curves were constructed in the
      absence and presence of GR32191 and glibenclamide and pKB values calculated.
      GR32191 caused significant rightward shifts in U46619 concentration-response
      curves and was a more potent antagonist in guinea-pig vessels (pKB approximately
      9.4) than rat arteries (pKB approximately 7.9). Conversely, glibenclamide failed
      to inhibit contractions to U46619 in guinea-pig vessels but antagonised responses
      to U46619 in rat aorta (pKB = 6.1) and mesenteric artery (pKB = 6.3). In
      combination, GR32191 and glibenclamide caused a shift in the concentration-effect
      curve to U46619 in rat aorta that was additive. These results suggest that
      glibenclamide can discriminate between species differences in thromboxane A2
      receptors and may exert its inhibitory effect upon U46619-mediated contractions
      at the level of the thromboxane A2 receptor.

PMID- 9754919
TI  - Possible mechanism for the anemia induced by candesartan cilexetil (TCV-116), an
      angiotensin II receptor antagonist, in rats.
AB  - Candesartan cilexetil (TCV-116), an angiotensin II receptor antagonist, was
      administered orally to male F344/Jcl and Crj:CD (SD) rats at 1000 mg kg(-1) day(
      1) for 1-28 days, and the possible mechanism for the anemia induced by TCV-116
      was investigated. In the TCV-116 group, the erythrocyte count, hematocrit value
      and hemoglobin concentration were decreased by 7-8% as compared with the values
      in the control group after dosing for 28 days. The plasma and renal
      erythropoietin levels, the reticulocyte count in the peripheral blood and the
      erythroid cell count upon bone marrow examination were decreased on day 7, but
      there were no accompanying histopathological renal lesions. Renal blood flow was
      increased, and mean blood pressure was decreased after TCV-116. These results
      suggest that the primary cause of the anemia induced by TCV-116 treatment is the
      increase in renal blood flow followed by a decrease in erythropoietin production.

PMID- 9754920
TI  - Anti-ulcer effects of antioxidants: effect of probucol.
AB  - We investigated the effect of probucol, a lipid-lowering agent with antioxidant
      properties, on HCl plus ethanol-induced gastric mucosal injury and on the healing
      of acetic acid-induced gastric ulcers in rats. When the free radical-scavenging
      activity of probucol was measured by an electron spin resonance technique, the
      agent (10(-5)-10(-3) M) scavenged both superoxide anions and hydroxyl radicals.
      Oral administration of probucol (250-1000 mg/kg) dose dependently prevented the
      HCl plus ethanol-induced gastric mucosal injury and the increase in
      thiobarbituric acid-reactive substances, an index of lipid peroxidation, in the
      injured mucosa. Repeated oral administration of probucol (250-1000 mg/kg twice
      daily) dose dependently accelerated the healing of acetic acid-induced gastric
      ulcers. In addition, probucol already inhibited the increase in the content of
      thiobarbituric acid-reactive substances in the ulcerated region before the ulcer
      healing effect of this agent was recognized. These results suggest that probucol
      may partly protect gastric mucosa from acute gastric mucosal injury and promote
      the healing of chronic gastric ulcers by its antioxidant activity.

PMID- 9754921
TI  - Glucocorticosteroids and in vitro effects on chemiluminescence of isolated bovine
      blood granulocytes.
AB  - The effects of glucocorticosteroids on respiratory burst of bovine granulocytes
      were studied in vitro by means of (1) chemiluminescence (luminol-dependent,
      phorbol 12-myristate 13-acetate (PMA)-stimulated), (2) a cell-free
      chemiluminescence assay, and (3) a myeloperoxidase assay. Significant effects on
      cellular chemiluminescence were only observed at the highest, not obtainable in
      vivo, concentration for all drugs except betamethasone. Prednisolone induced
      inhibition at therapeutic doses. Also, flumethasone and dexamethasone induced
      significant inhibition at lower concentrations. In the cell-free assay, all
      glucocorticosteroids, except betamethasone, inhibited chemiluminescence at high
      concentrations. None of the glucocorticosteroids tested affected myeloperoxidase
      activity. The results indicated that the drugs do not affect NADPH-oxidase
      activity. The adverse effects may be due to scavenging of free oxygen radicals,
      or to interference with the interaction between luminol and the myeloperoxidase
      H2O2-halide system. It can be concluded that most glucocorticosteroids show no
      adverse effects on the respiratory burst of bovine granulocytes in vitro at
      therapeutical concentrations.

PMID- 9754922
TI  - 2-Phenyl-4-quinolone prevents serotonin-induced increases in endothelial
      permeability to albumin.
AB  - To investigate the role of 2-phenyl-4-quinolone in enhancing endothelial
      monolayer paracellular barrier function and preventing the disturbance of
      paracellular barrier function by vasoactive agents, the study examined the effect
      of 2-phenyl-4-quinolone on serotonin-mediated macromolecule transfer and
      microfilament changes in cultured rat heart endothelial cells. Serotonin-treated
      endothelial cells induced concentration-dependent increases in the passage of
      Evans blue dye-bound bovine serum albumin. Incubation of the endothelial
      monolayers with 2-phenyl-4-quinolone antagonized serotonin- and cytochalasin B
      induced macromolecular permeability. 2-Phenyl-4-quinolone also opposed the effect
      of serotonin or cytochalasin B on the distribution and quantity of actin
      filaments in the endothelial cytoskeleton. Furthermore, 2-phenyl-4-quinolone
      alone led to an apparent quantitative increase in F actin fluorescence in
      endothelial cells. The addition of 10(-7) M 2-phenyl-4-quinolone had an effect on
      serotonin-induced changes in the myosin and distribution of myosin were
      comparable to that on serotonin monolayers. In conclusion, 2-phenyl-4-quinolone
      attenuated the serotonin-induced permeability of rat heart endothelial cells and
      this was associated with stabilization of F actin microfilaments and changes in
      the myosin organization. This result suggests that influences on cytoskeletal
      assembly may be involved in this process.

PMID- 9754923
TI  - Modulation of the chemotactic peptide- and immunoglobulin G-triggered respiratory
      burst in human neutrophils by exogenous and endogenous adenosine.
AB  - The effects of exogenous and endogenous adenosine on the production of oxygen
      metabolites in neutrophils triggered by the chemotactic peptide N-formyl
      methionyl-leucyl-phenylalanine (fMLP) or immunoglobulin G (IgG)-opsonized yeast
      particles, were investigated. By using luminol-enhanced chemiluminescence, we
      found that adenosine A1 receptor activation did not affect, whereas adenosine A
      receptor activation, through a mechanism involving the cyclic AMP (cAMP)-protein
      kinase A signalling pathway, both inhibited the fMLP- and IgG-triggered
      respiratory burst. The adenosine-induced inhibition was however more pronounced
      after exposure to fMLP than to IgG-yeast. Stimulation with fMLP caused an
      extracellular accumulation of endogenous adenosine, which indicates that this
      event is a negative-feedback mechanism preventing an uncontrolled activation of
      chemoattractant-stimulated neutrophils. On the contrary, exposure of neutrophils
      to IgG-yeast did not appear to accumulate extracellular adenosine, probably due
      to increased adenosine deaminase activity during phagocytosis. In conclusion,
      this work accentuates the importance of adenosine, both exogenously applied and
      endogenously formed, as an inflammatory agent modulating the respiratory burst
      during the different phases in neutrophil activation.

PMID- 9754924
TI  - Apparent thermodynamic parameters of ligand binding to the cloned rat mu-opioid
      receptor.
AB  - The apparent thermodynamic parameters of binding of ten ligands to the cloned rat
      mu-opioid receptor stably expressed in Chinese hamster ovary (CHO) cells were
      investigated. For every ligand, the Kd or Ki values at 0 degrees C, 12 degrees C,
      25 degrees C and 37 degrees C were determined, a van't Hoff plot was generated
      and deltaH degrees' , deltaS degrees' and -TdeltaS degrees' and deltaG degrees'
      were calculated. Changes in free energy (deltaG degrees') ranged from -10.35 to 
      15.65 kcal/mol. The binding of sufentanil, ohmefentanyl, diprenorphine and D-Phe
      Cys-Tyr-D-Trp-Arg-Thr-penicillamineThr-NH2 (CTAP) was endothermic (deltaH
      degrees' > 0) and driven by an increase in entropy (-TdeltaS degrees' = -13.08 to
      -18.57 kcal/mol). The binding of naltrexone was exothermic (deltaH degrees' = 
      12.56 kcal/mol) and essentially enthalpy-driven. The binding of morphine,
      methadone, pentazocine, [D-Ala2, NMePhe4, Gly-ol]enkephalin (DAMGO) and Tyr-Pro
      NMePhe-D-Pro-NH2 (PL017) was exothermic (deltaH degrees' = -3.53 to -9.95
      kcal/mol) and occurred with an increase in entropy (-TdeltaS degrees' = -2.48 to 
      7.92 kcal/mol). Plots of enthalpy versus entropy and enthalpy versus free energy
      were linear, although enthalpy-entropy compensation was not evident. The entropy
      changes were not correlated with apparent lipophilicity of the compounds. These
      results suggest that: (1) opioid ligands bind to the mu receptor by specific
      mechanisms, unrelated to lipid solubility; (2) the mechanism of binding is not
      universally different for peptide and non-peptide ligands; (3) the nature of
      binding does not a priori determine intrinsic activity. The results reveal a
      novel differentiation of opioid ligands into two groups (group 1: ohmefentanyl,
      sufentanil, diprenorphine, CTAP and PL017; group 2: naltrexone, morphine,
      methadone, DAMGO, pentazocine), based on two distinct relationships between
      enthalpy versus free energy of binding, the details of which are yet to be
      elucidated.

PMID- 9754925
TI  - Ethanol affects the function of a neurotransmitter receptor protein without
      altering the membrane lipid phase.
AB  - Using patch-clamp and fluorescence techniques we found that ethanol (10-200 mM)
      potentiated strychnine-sensitive glycine receptors without having detectable
      effects on lipid order parameters in mouse spinal cord neurons. Hepthanol (0.01-1
      mM), in contrast, did not affect the glycine current, but it altered the core and
      surface of spinal neuron membranes as detected by changes in 1,6-diphenyl-1,3,5
      hexatriene (DPH) and Laurdan fluorescence parameters. These findings support the
      idea that ethanol affects these membrane proteins without changing lipid
      fluidity.

PMID- 9754926
TI  - 2-Hydroxycarbazole induces Ca2+ release from sarcoplasmic reticulum by activating
      the ryanodine receptor.
AB  - 2-Hydroxycarbazole was shown to induce Ca2+ release from skeletal muscle and
      cardiac muscle sarcoplasmic reticulum at concentrations between 100-500 microM.
      This release was blocked by both 1 mM tetracaine and 30 microM ruthenium red
      which inhibit the ryanodine receptor or by pre-treatment with 10 mM caffeine
      which depletes the ryanodine receptor-containing Ca2+ stores. This, in addition
      to the fact that 2-hydroxycarbazole has little effect on Ca2+ ATPase activity,
      indicates that it activates Ca2+ release through the ryanodine receptor. The
      apparent EC50 value for release from both skeletal muscle and cardiac muscle
      sarcoplasmic reticulum was approximately 200 microM and maximal release occurred
      at 400-500 microM, making it approximately 20 times more potent than caffeine.
      The dose-dependency in the extent of Ca2+ release induced by 2-hydroxycarbazole
      was also apparently highly cooperative for both preparations. That 2
      hydroxycarbazole was able to mobilize Ca2+ from non-muscle cell microsomes and in
      intact TM4 cells (which contain ryanodine receptors), makes this compound a more
      potent and commercially available alternative to caffeine in studying the role of
      this intracellular Ca2+ channel in a variety of systems.

PMID- 9754927
TI  - Chicken GABA(A) receptor beta4 subunits form robust homomeric GABA-gated channels
      in Xenopus oocytes.
AB  - Chicken GABA(A) receptor beta4L and beta4S subunits were expressed in Xenopus
      oocytes by cRNA injection. Oocytes expressing either beta4 subunit alone or in
      combination with the chicken alpha1 subunit were studied using the two-electrode
      voltage-clamp technique. Both the beta4L and beta4S subunits form homomeric GABA
      gated Cl- channels with similar efficiencies. In comparison, oocytes expressing
      either the chicken alpha1 or beta2S polypeptide show no or barely detectable GABA
      responses, as reported by others for most single-subunit vertebrate GABA(A)
      receptors. The GABA-gated currents due to the beta4L-subunit homomer were not
      affected by the presence of actinomycin D during cRNA expression, indicating that
      nascent oocyte polypeptides are not required for channel formation. The homomeric
      beta4L-subunit receptors show high affinity for GABA with an EC50 value of 4.3 +/
      0.4 microM and a Hill coefficient of 1.1 +/- 0.1 (n = 6). In response to GABA
      application at the EC25 value, currents elicited from the beta4L-subunit receptor
      are enhanced by 50 microM pentobarbital (110 +/- 10%, n = 3) and 10 microM
      loreclezole (60 +/- 3%, n = 3), inhibited by 10 microM picrotoxinin (93 +/- 3%, n
      = 3), but not affected by 1 microM diazepam. These properties are similar to
      those found for oocytes expressing heteromeric chicken alpha1beta4L and
      alpha1beta2S receptors. Since the beta subunits of GABA(A) receptors provide
      essential determinants for receptor assembly and subcellular localization,
      homomeric beta4-subunit receptors are a useful model system for further study of
      the structure and function of GABA(A) receptors.

PMID- 9754928
TI  - Inhibition of ligand-gated cation-selective channels by tamoxifen.
AB  - The nonsteroidal antioestrogen tamoxifen has been shown to block a number of
      voltage-gated cation-selective channels but its effect on ligand-gated cation
      selective channels has not been studied. We have investigated the action of
      tamoxifen and the related derivative toremifene on ligand-gated cationic
      nicotinic acetylcholine and 5-HT3 receptor channels. Tamoxifen and toremifene
      both inhibited cationic currents of adult-type human muscle nicotinic
      acetylcholine receptors expressed in Xenopus oocytes with similar IC50 values of
      1.2 +/- 0.03 microM (nH = 0.84 +/- 0.02) and 1.2 +/- 0.1 microM (nH = 1.1 +/-
      0.1), respectively. Tamoxifen could also block native 5-HT3 receptors in NG108-15
      neuroblastoma/glioma hybrid cells with IC50 = 0.81 +/- 0.15 microM and nH of 1.3
      +/- 0.3. The characteristics of block by tamoxifen at the 5-HT3 receptor were
      voltage- and use-independent. The inhibition of the 5-HT-evoked currents were not
      overcome by increasing concentrations of 5-HT consistent with a noncompetitive
      mechanism of block.

PMID- 9754929
TI  - Effects of insulin-like growth factor I and II on DNA synthesis and proliferation
      in primary cultures of adult rat hepatocytes.
AB  - We compared the effects of insulin-like growth factor I (IGF-I) and II (IGF-II)
      on DNA synthesis and proliferation and investigated various signal transduction
      mechanisms involved in insulin-like growth factor-induced mitogenesis in primary
      cultures of adult rat hepatocytes. IGF-I stimulated hepatocyte DNA synthesis and
      proliferation with an EC50 of 75 ng/ml within 4 h of culture. These effects were
      sensitive to the IGF-I concentration and cell density. Hepatocyte proliferation
      induced by IGF-I was potentiated by metaproterenol (10(-6) M) as well as by 8
      bromo-cAMP, phorbol 12-myristate 13-acetate (PMA; 10(-8) M) and was inhibited by
      U-73122 (1-(-[[17beta-3-methoxyestra-1,3,5(10)-triene-17-yl]amino]hexyl]-+
      ++1Hpyrrol-2,5-dione)), genistein, wortmannin, PD98059 (2'-amino-3'
      methoxyflavone) and rapamycin. The IGF-I effect was independent of pertussis
      toxin (100 ng/ml). IGF-II also dose dependently stimulated hepatocyte DNA
      synthesis and proliferation with an EC50 of 0.75 ng/ml within 4 h of culture.
      However, these effects were not dependent on the initial plating density. The
      stimulatory effects of IGF-II were potentiated by UK-14304 (5-bromo-6-[2
      imidazolin-2-ylamino]-quinoxaline) (10(-5) M) and inhibited by phenylephrine,
      PMA, metaproterenol, 8-bromo-cAMP, PD98059, rapamycin, and pertussis toxin. The
      IGF-II effects were not affected by genistein, U-73122, and wortmannin. These
      results suggest that IGF-I and IGF-II rapidly stimulate the DNA synthesis and
      proliferation of adult rat hepatocytes by separate mechanisms.

PMID- 9754930
TI  - Amino acid residue 200 on the alpha1 subunit of GABA(A) receptors affects the
      interaction with selected benzodiazepine binding site ligands.
AB  - Mutant alph1 subunits of the GABA(A) receptor were coexpressed in combination
      with the wild-type beta2 and gamma2 subunits in human embryonic kidney (HEK) 293
      cells. The binding properties of various benzodiazepine site ligands were
      determined by displacement of ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H
      imidazo[1,5a]-[1,4]benzodia zepine-3-carboxylate ([3H]Ro 15-1788). The mutation
      G200E led to a decrease in zolpidem and 3-methyl-6-[3-(trifluoromethyl)phenyl]
      1,2,4-triazolo[4,3-b]pyridazine (CL 218872) affinity amounting to 16- and 8-fold.
      Receptors containing a conservative T206V substitution showed a 41- and 38-fold
      increase in methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) and
      CL 218872 affinity combined with a decrease in diazepam and zolpidem affinity,
      amounting to 7- and 10-fold. Two mutations, Q203A and Q203S showed almost no
      effects on the binding of benzodiazepine site ligands, indicating that this
      residue is not involved in the binding of benzodiazepines and related compounds.

PMID- 9754931
TI  - Studies on the teratogen pharmacophore of valproic acid analogues: evidence of
      interactions at a hydrophobic centre.
AB  - Propyl-4-yn-valproic acid (2-propyl-4-pentynoic acid), an analogue of valproic
      acid with a triple bond in one alkyl side chain, potently induces exencephaly in
      mice. Given that propyl-4-yn-valproic acid is a branched chain carboxylic acid,
      we synthesized a series of analogues with n-alkyl side chains of increasing
      length and correlated their potential to induce neural tube defects and to
      inhibit proliferation and induce differentiation in cells of neural origin, the
      latter being crucial to the orderly structuring of the embryo. All analogues
      significantly increased the incidence of neural tube defects in the embryos of
      dams exposed to a single dose of 1.25 mmol/kg on day 8 of gestation. This effect
      occurred in a dose-dependent manner and the rate of exencephaly increased with
      the progressive increase in n-alkyl side chain length. Moreover, increasing chain
      length resulted in a dose-dependent inhibition of C6 glioma proliferation rate
      over a concentration range of 0-3 mM and this was independent of the cell type
      employed and mode of estimating proliferative rate. The antiproliferative action
      of these analogues was associated with profound shape change in neuro-2A
      neuroblastoma involving extensive neuritogenesis and an associated increase in
      neural cell adhesion molecule (NCAM) prevalence at points of cell-cell contact,
      the latter exhibiting a dose-dependent increase when the n-alkyl chain was
      extended to five carbon units. These results suggest an interaction with a
      specific site in which the n-alkyl side is proposed to serve as an 'anchor'
      within a hydrophobic pocket to facilitate the ionic and/or H-bonding of the
      carboxylic acid and high electron density of the carbon-carbon triple bond.

PMID- 9754932
TI  - Sigma receptor ligands (+)-SKF10,047 and SA4503 improve dizocilpine-induced
      spatial memory deficits in rats.
AB  - This study examined the effects of the sigma receptor ligands (+)-N
      allylnormetazocine ((+)-SKF10,047) and 1-(3,4-dimethoxyphenethyl)-4-(3
      phenylpropyl)piperazine dihydrochloride (SA4503) on dizocilpine-induced
      impairment of working and reference memory in a radial arm maze task in rats.
      Dizocilpine, a non-competitive NMDA receptor antagonist, significantly impaired
      both reference and working memory, an effect which was accompanied by ataxia and
      impairment of food intake. The dizocilpine-induced impairment of reference memory
      was dose-dependently attenuated by (+)-SKF10,047 and SA4503. SA4503 also
      attenuated the dizocilpine-induced working memory impairment, although (+)
      SKF10,047 had no effect. Neither sigma receptor ligand affected the behavioral
      symptoms such as ataxia and impairment of food intake induced by dizocilpine. The
      ameliorating effects of both (+)-SKF10,047 and SA4503 on dizocilpine-induced
      spatial memory impairment were completely antagonized by a sigma1 receptor
      antagonist N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine-mon
      ohydrochloride. These results suggest that the interaction of sigma1 receptors
      with NMDA receptors modulates spatial memory in rats.

PMID- 9754933
TI  - Vasopressin opposes locomotor stimulation by ethanol, cocaine and amphetamine in
      mice.
AB  - The effects of arginine8-vasopressin on the stimulation of locomotor activity
      induced by ethanol, cocaine and amphetamine were examined in DBA/2N mice.
      Locomotor activity was measured by photocell beam interruption for a period of 45
      min following ethanol, cocaine or amphetamine administration. Pretreatment with
      vasopressin alone in a dose of 2 (but not 1) microg/mouse s.c. reduced locomotor
      activity. The low dose of vasopressin did not modify the stimulation of locomotor
      activity induced by i.p. administration of ethanol in doses of either 1.5 or 2
      g/kg. The high dose of vasopressin reduced locomotor activity induced by both
      doses of ethanol, in an apparently additive manner. Cocaine in doses of 15 and 20
      mg/kg strongly stimulated locomotor activity, but this stimulation was completely
      antagonized by pretreatment with 1 microg of vasopressin. Similarly, the
      stimulation of locomotor activity induced by amphetamine (5 mg/kg) was also
      blocked by pretreatment with vasopressin. These findings raise the possibility
      that the effect of vasopressin varies with the extent and nature of dopaminergic
      involvement in the drug-induced stimulation of activity. For drugs like cocaine
      or amphetamine which stimulate locomotor activity primarily through the
      mesolimbic dopaminergic system, vasopressin can completely antagonize the
      stimulation. For ethanol, which stimulates locomotor activity through action on a
      number of other neurotransmitters as well as dopamine, vasopressin treatment only
      reduces its stimulation of locomotor activity in an additive manner. These
      results suggest a close interaction between vasopressin and dopamine action.

PMID- 9754934
TI  - Cocaine sensitization prevents the hypolocomotor effects of high but not low
      doses of PD 128,907.
AB  - In this study we examined the effects of the preferential dopamine D3 receptor
      agonist S(+)-(4aR,10bR)-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]b enzopyrano-[4,3
      b]-1,4-oxazin-9-ol (PD 128,907) on locomotion in mice sensitized to cocaine. In
      mice repeatedly treated with saline, PD 128,907 induced hypoactivity over a wide
      dose range (0.01-40 mg/kg); however, after repeated treatment with 40 mg/kg
      cocaine, higher doses of PD 128,907 (2.5-40 mg/kg) no longer induced hypoactivity
      whereas the effects of lower doses (0.01-0.16 mg/kg) were not altered. Because
      lower doses of PD 128,907 are thought to induce hypoactivity via activation of
      dopamine D3 receptors, the present data suggest that, under conditions where
      cocaine induces marked sensitization to its locomotor effects, the sensitivity of
      these receptors is not altered. In contrast, because higher doses of PD 128,907
      can activate dopamine D2 receptors, it is conceivable that apparent cross
      sensitization to its dopamine D2 receptor agonist properties is responsible for
      the lack of hypolocomotor effects at high doses. Overall, the results indicate
      that altered dopamine D3 receptor sensitivity does not play an important role in
      the expression of cocaine-induced sensitization.

PMID- 9754935
TI  - Effects of nonintermittent treatment of rabbits with pentaerythritol tetranitrate
      on vascular reactivity and superoxide production.
AB  - Pentaerythritol tetranitrate is an organic nitrate ester that undergoes
      metabolization to pentaerythritol, pentaerythritol trinitrate, pentaerythritol
      dinitrate and pentaerythritol mononitrate. Recent data suggested that
      pentaerythritol tetranitrate is endowed with vasoprotective activities in
      experimental atherosclerosis. This study was undertaken to gain insight into the
      underlying mechanism. The basic mechanism of action of all pentaerythritol
      nitrates was evaluated by measuring liberation of nitric oxide (NO), stimulation
      of human soluble guanylate cyclase and vasorelaxation in rabbit aorta. A
      subsequent in vivo study in New Zealand White rabbits was performed to
      investigate the effects of a 4 months lasting nonintermittent oral treatment with
      6 mg pentaerythritol tetranitrate kg(-1) day(-1) on vascular superoxide
      production, endothelium dependent vasorelaxation and vasorelaxation to
      pentaerythritol tetranitrate itself. The formation rates of NO from the
      pentaerythritol nitrates (100 microM, n = 5) in presence of 5 mM cystein were (in
      nM min(-1)): 62.1 +/- 3.2 (pentaerythritol tetranitrate), 21.3 +/- 0.9
      (pentaerythritol trinitrate), 6.4 +/- 0.6 (pentaerythritol dinitrate) and 3.2 +/-
      0.4 (pentaerythritol mononitrate). Similarly, the pD2 values (-log M) for half
      maximal activation of soluble guanylate cyclase decreased from pentaerythritol
      tetranitrate (3.391 +/- 0.09, n = 4) to pentaerythritol mononitrate (2.655 +/-
      0.04, n = 3) as did the pD2 values (in -log M) for half-maximal relaxation of
      rabbit aortic rings (n = 7) from pentaerythritol tetranitrate (8.3 +/- 0.17) to
      pentaerythritol mononitrate (5.0 +/- 0.11). Significant correlations were found
      between the NO formation rates and the pD2 values for enzyme stimulation (r =
      0.98, P = 0.002) and vasorelaxation (r = 0.90, P = 0.049) suggesting that these
      effects of the pentaerythritol nitrates were mediated by NO. The results of the
      in vivo study showed that aging induces a significant increase of aortic
      superoxide production (median values, n = 10) from 2.45 nM mg(-1) min(-1) (age 7
      months) to 3.39 nM mg(-1) min(-1) (age 11 months, P < 0.01) that was prevented by
      concurrent treatment with pentaerythritol tetranitrate (2.76 nM mg(-1) min(-1)).
      In vitro vasorelaxation to pentaerythritol tetranitrate was identical in all
      groups indicating absence of nitrate tolerance. Endothelium-dependent
      vasorelaxation was also identical in all groups. These data suggest that oral
      treatment with pentaerythritol tetranitrate reduces vascular oxidant stress by an
      NO-dependent pathway, which may contribute to the vasoprotective activity of
      pentaerythritol tetranitrate in experimental atherosclerosis.

PMID- 9754936
TI  - Chronic infusion of adrenomedullin reduces pulmonary hypertension and lessens
      right ventricular hypertrophy in rats administered monocrotaline.
AB  - A novel vasorelaxant peptide, adrenomedullin, its messenger ribonucleic acid
      (mRNA), and the mRNA for its receptor are highly expressed in the lung,
      suggesting that adrenomedullin may play a role in the regulation of the pulmonary
      circulation. We investigated whether the chronic infusion of rat adrenomedullin
      would affect pulmonary hypertension and right ventricular hypertrophy produced by
      the administration of monocrotaline. Four-week-old male Wistar rats received a
      single subcutaneous injection of 60 mg/kg monocrotaline and were then chronically
      and subcutaneously infused with rat adrenomedullin (PH + AM group, n = 8) or
      saline (PH group, n = 10) by an osmotic minipump for a period of 21 days. Plasma
      levels of adrenomedullin were significantly higher in the PH vs. the control
      group. The chronic infusion of adrenomedullin in rats with pulmonary hypertension
      increased the plasma levels of adrenomedullin to a value 94% greater than that of
      the control group and 55% greater than that of the untreated PH group. Chronic
      infusion of adrenomedullin significantly lessened the increase in right
      ventricular systolic pressure and the ratio of right ventricular weight to body
      weight seen after monocrotaline treatment. Histological examination revealed that
      adrenomedullin also attenuated the medial thickening of the pulmonary artery.
      These results suggest that chronic infusion of adrenomedullin attenuates the
      pulmonary hypertension and right ventricular hypertrophy seen in rats treated
      with monocrotaline.

PMID- 9754937
TI  - Vasopressin receptors involved in adrenergic neurotransmission in the circular
      muscle of the human vas deferens.
AB  - We studied the effects of vasopressin on the adrenergic responses of in vitro
      preparations of circular muscle from the vas deferens obtained from 28 men
      undergoing elective vasectomy. Vasopressin (3 x 10(-9)-3 x 10(-8) M) enhanced the
      phasic contractions elicited by electrical field stimulation and noradrenaline.
      This potentiation was blocked by the vasopressin V1 receptor antagonist
      d(CH2)5Tyr(Me)vasopressin (10(-6) M) but not by the vasopressin V2 receptor
      antagonist [d(CH2)5, D-Ile2,Ile4,Arg8]vasopressin (10(-6) M). The Ca2+ antagonist
      nifedipine (10(-6) M) did not affect the potentiation of electrical field
      stimulation induced by vasopressin and noradrenaline but reduced KCl-induced
      contractions and abolished the induction of phasic activity by vasopressin in the
      presence of KCl. The results demonstrate that vasopressin, in addition to its
      direct contractile effects, strongly potentiates contractions of human vas
      deferens elicited by adrenergic stimulation. Both the direct and indirect effects
      of vasopressin appear to be mediated by vasopressin V1 receptor stimulation and
      are independent of Ca2+ entry through dihydropyridine Ca2+ channels.

PMID- 9754938
TI  - Facilitation by endogenous acetylcholine and nitric oxide of luminal serotonin
      release from the guinea-pig colon.
AB  - The present study was designed to determine the influence of endogenous
      acetylcholine and nitric oxide (NO) on spontaneous luminal serotonin (5
      hydroxytryptamine, 5-HT) release in the luminally perfused isolated guinea-pig
      proximal colon in vitro. 5-HT was determined by high-performance liquid
      chromatography with electro-chemical detection. The luminal outflow of 5-HT was
      significantly reduced by atropine (0.2 microM), hexamethonium (100 microM), the
      NO synthase inhibitor NG-nitro-L-arginine (L-NNA, 10 microM) and the NO-trapping
      agent 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (carboxy
      PTIO, 30 microM). Addition of excess L-arginine (300 microM) reversed the
      inhibitory effect of L-NNA on the 5-HT outflow. Physostigmine (1 microM) caused a
      great increase (atropine-sensitive) in 5-HT outflow. The enhancing action of
      physostigmine on 5-HT outflow was partially inhibited by L-NNA (100 microM) or
      carboxy-PTIO (30 microM), but was unaffected by the muscarinic M1 receptor
      antagonist pirenzepine (0.2 microM) or a muscarinic M3 receptor antagonist 4
      diphenyl-acetoxy-N-methyl-piperidine methiodide (0.2 microM). These results
      suggest that 5-HT release from luminally perfused proximal colon of the guinea
      pig is stimulated via a NO pathway and cholinergic pathways which utilize
      muscarinic synapses and nicotinic synapses. Further, an intrinsic cholinergic-NO
      link appears to play a role in the stimulation of luminal 5-HT release, which may
      reflect the release of 5-HT from entero-chromaffin cells.

PMID- 9754939
TI  - Pulmonary actions of anandamide, an endogenous cannabinoid receptor agonist, in
      guinea pigs.
AB  - Anandamide (arachidonylethanolamide), 5,8,11,14-eicosatetraenamide, (N-2
      hydroxyethyl), was tested for bronchodilator and anti-inflammatory activities.
      Conscious guinea pigs were given cumulative i.v. doses of anandamide (1.0, 3.0,
      and 10.0 mg/kg) to assess its effect on dynamic compliance (Cdyn), total
      pulmonary resistance (RL), tidal volume (VT) and breathing frequency (f). Other
      guinea pigs were exposed to an aerosol of A23187 (6S
      [6alpha(2S*,3S*),8beta(R*),9beta,11alpha]-5- (methylamino)-2-[[3,9,11-trimethyl-8
      [1-methyl-2-oxo-2-(1H-pyrrol-2-yl)e thyl]-1,7-dioxaspiro[5.5]undec-2-yl]methyl]-4
      benzoxazole carboxylic acid) until Cdyn decreased by 50% (approximately 5 min)
      and at 20 min, cumulative i.v. doses of anandamide (1.0, 3.0, and 10.0 mg/kg)
      were administered and reversal of Cdyn examined. After the final dose of
      anandamide, the animals were killed and excised lung gas volumes (ELGV), i.e.,
      pulmonary gas trapping, measured. Other animals were treated i.v. with anandamide
      (10.0 mg/kg), exposed to an aerosol of A23187 until labored breathing began, and
      then killed 1 h later. Anandamide did not significantly affect Cdyn, RL, VT and
      f. ELGV values of anandamide-treated guinea pigs were not different from those of
      vehicle-treated animals. Anandamide failed to reverse A23187-induced decreases in
      Cdyn and to reduce A23187-associated ELGV increases. Also, it did not prevent the
      prolonged airway obstruction caused by A23187. Histological evaluation revealed
      that anandamide significantly reduced A23187-related airway epithelial injury and
      pulmonary leukocytosis. However, it did not prevent A23187-induced
      peribronchiolar granulocytic accumulation. Our results suggest that in vivo
      anandamide has minimal direct airway smooth muscle-related actions, however it
      may possess modest anti-inflammatory properties.

PMID- 9754940
TI  - Characterisation of new efaroxan derivatives for use in purification of
      imidazoline-binding sites.
AB  - The insulin secretagogue activity of certain imidazoline compounds is mediated by
      a binding site associated with ATP-sensitive K+ (K(ATP)) channels in the
      pancreatic beta-cell. We describe the effects of a series of structural
      modifications to efaroxan on its activity at this site. Substitution of amino-,
      nitro- or azide- groups onto the 5-position of the benzene ring of efaroxan did
      not significantly affect the functional interaction of the ligand with the islet
      imidazoline binding site. Modification of the imidazoline ring to an imidazole to
      generate 2-(2-ethyl-2,3-dihydrobenzo[b]furan-2-yl)-1H-imidazole (KU14R) resulted
      in loss of secretagogue activity. Indeed, this reagent appeared to act as an
      imidazoline antagonist since it blocked the secretory responses to imidazoline
      compounds and also inhibited the blockade of beta-cell K(ATP) channels by
      efaroxan in patch clamp experiments. Application of KU14R alone resulted in a
      modest reduction in K(ATP) channel opening, suggesting that it may display weak
      partial agonism, at least in patch-clamp experiments.

PMID- 9754941
TI  - Picotamide, an antithromboxane agent, inhibits the migration and proliferation of
      arterial myocytes.
AB  - Picotamide is an antiplatelet drug with a peculiar dual mechanism of action: it
      inhibits thromboxane A2 synthase and antagonizes the pharmacological responses
      mediated by thromboxane A2 receptor. We investigated the in vitro effect of
      picotamide on smooth muscle cell migration and proliferation. Picotamide (1-500
      microM) decreased human and rat smooth muscle cell proliferation, evaluated as
      cell number, in a concentration-dependent and reversible manner. Picotamide
      inhibited DNA synthesis induced by fetal calf serum (10%), platelet-derived
      growth factor (PDGF-BB (20 ng/ml)), epidermal growth factor (EGF (1 nM)) and
      (15S)-hydroxy-11,9-(epoxymethano)prosta-5Z,13E-dienoic acid (U46619 (10 microM,
      thromboxane A2 receptor agonist)). Co-incubation of U46619 together with EGF or
      PDGF-BB resulted in a marked amplification of [3H]thymidine incorporation that
      was completely reversed by picotamide. The drug also inhibited smooth muscle cell
      migration induced by fibrinogen (600 microg/ml) or PDGF-BB (20 ng/ml) in a
      concentration-dependent manner. The ability of picotamide to interfere with
      myocyte migration and proliferation confers, at least in vitro, a pharmacological
      interest on the compound in atherogenesis.

PMID- 9754942
TI  - Involvement of G-protein betagamma subunits in coupling the adenosine A1 receptor
      to phospholipase C in transfected CHO cells.
AB  - In transfected Chinese hamster ovary (CHO-A1) cells the human adenosine A1
      receptor directly stimulates pertussis toxin-sensitive increases in inositol
      phosphate production and potentiates (synergistically) the inositol phosphate
      responses mediated by Gq-coupled P2Y2 purinoceptor and CCK(A) receptors. In the
      present study we have investigated the role of Gbetagamma subunits in mediating
      adenosine A1 receptor effects on phospholipase C activation (both direct and
      synergistic) by transiently transfecting CHO-A1 cells with a scavenger of
      Gbetagamma subunits: the C-terminus of beta-adrenoceptor kinase 1 (beta ark1
      residues 495-689). [3H]inositol phosphate responses to the selective adenosine A1
      receptor agonist N6-cyclopentyladenosine (CPA; 1 microM) were inhibited (41 +/-
      1%) in CHO-A1 cells transiently transfected with the Gbetagamma scavenger, beta
      ark1 (495-689). Expression of beta ark1 (495-689) protein was confirmed by
      Western blotting. In contrast, adenosine A1 receptor-mediated inhibition of
      forskolin stimulated [3H]cyclic AMP accumulation was unaffected by transient
      expression of beta ark1 (495-689). Beta ark1 (495-689) expression had no
      significant effect on the [3H]inositol phosphate responses produced by activation
      of the endogenous P2Y2 purinoceptor (100 microM UTP; 92 +/- 0.8% of control).
      [3H]inositol phosphate accumulation in response to adenosine A receptor
      activation was also attenuated in CHO-K1 cells co-transfected with the beta ark1
      (495-689) minigene (59 +/- 4% inhibition of control response to 1 microM CPA).
      Finally, transient expression of beta ark1 (495-689) in CHO-A1 cells inhibited
      the augmentation of [3H]inositol phosphate responses resulting from co-activation
      of adenosine A1 receptors and P2Y2 purinoceptors. These experiments indicate that
      Gbetagamma subunits are involved in the direct coupling the adenosine A1 receptor
      to phospholipase C and that they also participate in the augmentation of P2Y2
      purinoceptor-mediated [3H]inositol phosphate responses by the adenosine A1
      receptor.

PMID- 9754943
TI  - The 5-HT1A receptor agonist BAY x 3702 prevents staurosporine-induced apoptosis.
AB  - The 5-HT1A receptor agonist (-)-(R)-2-[4-[[(3,4-dihydro-2H-1-benzopyran-2
      yl)methyl]amino]butyl]-1,2 -benzisothiazol-3(2H)-one1,1-dioxide monohydrochloride
      (BAY x 3702) was recently shown to have pronounced neuroprotective effects in rat
      models of cerebral ischemia and traumatic brain injury. In the present study we
      investigated the neuroprotective effects of BAY x 3702 in primary cultures of
      hippocampal and cortical neurons. Cell death was induced by 25 nM of the
      apoptosis inducing agent staurosporine and analyzed 24 h later by release of
      lactate dehydrogenase, formation of apoptotic bodies and DNA fragmentation. A
      significant neuroprotection was seen after pretreatment of the affected neurons
      with 50 pM to 1 microM BAY x 3702. The effects of BAY x 3702 were completely
      blocked by the selective 5-HT1A receptor antagonist N-(2-(4-(2-methoxyphenyl)-1
      piperazinyl)ethyl)-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride) (WAY
      100635). These results indicate that low concentrations of BAY x 3702 protect
      cortical as well as hippocampal neurons from apoptotic cell death via a 5-HT1A
      receptor mediated pathway.

PMID- 9754944
TI  - Use of a spreadsheet to quantitate the equilibrium binding of an allosteric
      modulator.
AB  - Using the program Microsoft EXCEL, a spreadsheet was developed for constrained,
      simultaneous analysis of multiple datasets obtained from equilibrium binding
      experiments, according to an allosteric model of interaction. This approach was
      used to quantitate the interaction between the modulator (heptane-1,7-bis
      (dimethyl 3'-phthalimidopropyl) ammonium bromide) (C7/3-phth) and the
      radioligands [3H]N-methylscopolamine and [3H]quinuclidinyl benzilate at cortical
      and atrial muscarinic receptors. The interaction between various concentrations
      of the radioligands and C7/3-phth, in the guinea pig atrium and in the rat
      cerebral cortex, could be well described by the allosteric model. The affinity of
      C7/3-phth for unoccupied atrial receptors was significantly higher than for
      cortical receptors. The negative cooperativity between [3H]quinuclidinyl
      benzilate and the modulator was higher in cortex than that between the modulator
      and [3H]N-methylscopolamine. It is suggested that the described method has wide
      applicability because of the extensive availability of spreadsheet programs, the
      analytical advantages offered by constrained, simultaneous nonlinear regression
      and the ability to adapt the spreadsheet to almost any model of ligand-receptor
      interaction.

PMID- 9754945
TI  - No heroin or morphine 6beta-glucuronide analgesia in mu-opioid receptor knockout
      mice.
AB  - Recent reports suggest that heroin and its metabolite morphine 6beta-glucuronide
      can produce analgesia independent of the morphine-preferring mu-opioid receptor.
      We have tested heroin and morphine 6beta-glucuronide analgesia in wild-type,
      homozygous and heterozygous mu-opioid receptor knockout mice. Homozygotes display
      no heroin or morphine 6beta-glucuronide analgesia. Heterozygous mice with one mu
      opioid receptor gene copy reveal reduced heroin and morphine 6beta-glucuronide
      analgesia. The mu-opioid receptor-dependence of heroin and morphine 6beta
      glucuronide fails to support a requirement for a heroin-specific opiate receptor
      subtype.

PMID- 9754946
TI  - Recent developments in HIV protease inhibitor therapy.

PMID- 9754947
TI  - Suppression of recurrent genital herpes simplex virus type 2 infection by Rhus
      javanica in guinea pigs.
AB  - Rhus javanica has been shown to exhibit anti-herpes simplex virus (HSV) activity
      and potentiate the anti-HSV activity of acyclovir in vitro and in vivo. This
      extract was examined for its suppressive efficacy on recurrent genital infection
      in guinea pigs. Guinea pigs were primarily infected intravaginally with HSV type
      2 (HSV-2). Prophylactic oral administration, at the dose corresponding to human
      use, of R. javanica significantly reduced the incidence, severity and/or
      frequency of spontaneous and severe skin lesions as compared with latently
      infected guinea pigs administered with water. This prophylactic efficacy was
      confirmed by the crossover administration, for more than 2 months, of R. javanica
      and water to the infected guinea pigs. Toxicity, such as weight loss, from R.
      javanica administration was not observed in the guinea pigs. When recurrent HSV-2
      disease was induced by ultraviolet irradiation 3 months after primary infection,
      the prophylaxis with R. javanica was also significantly effective in reducing the
      severity of ultraviolet-induced skin lesions. Thus, prophylaxis of recurrent
      genital HSV-2 infection with R. javanica may preserve the efficacy of acyclovir
      by reducing both the use of acyclovir and the appearance of acyclovir-resistant
      viruses.

PMID- 9754948
TI  - The antiviral activity of the ribonucleotide reductase inhibitor BILD 1351 SE in
      combination with acyclovir against HSV type-1 in cell culture.
AB  - BILD 1351 SE is a selective peptidomimetic subunit association inhibitor of the
      herpes simplex virus (HSV) ribonucleotide reductase (RR) with potent antiviral
      activity both in cell culture assays and animal models of HSV disease. The
      ability of BILD 1351 SE to inhibit the replication of HSV-1 when used in
      combination with acyclovir (ACV) for the treatment of HSV infections was
      investigated in baby hamster kidney cells using a 96-well enzyme-linked
      immunosorbent assay. The effective concentrations to achieve 50% inhibition
      (EC50) of virus replication by BILD 1351 SE in serum-starved and non serum
      starved cells were 2 +/- 0.9 and 4.1 + 1.6 microM, respectively. The EC50 of ACV
      under both assay conditions was equal to 2.7 +/- 0.9 microM when tested alone.
      However, upon addition of BILD 1351 SE, the antiviral activity of ACV was
      potentiated in a synergistic manner as determined by the isobole method. At a
      concentration of BILD 1351 SE that produced 30% inhibition of HSV-1 replication,
      the EC50 of ACV decreased by about 15-fold in confluent cells and 17-fold in
      serum-starved cells. Similar conclusions were reached when evaluating drug
      interactions by the median dose-effect. Assuming mutually non-exclusive
      conditions at a drug ratio of ACV/BILD 1351 SE of 1/2, synergy was demonstrated
      in confluent cells with a drug enhancement index at EC50 of 14 and a combination
      index of 0.25. None of the drug combinations tested showed increased cytotoxicity
      in comparison with each drug alone. These results are consistent with the
      expected mode of action of a selective HSV RR inhibitor and support the strategy
      of combining these inhibitors with ACV for improved therapy of HSV infections.

PMID- 9754949
TI  - The sequential occurrence of pol 215 and pol 41 zidovudine resistance mutations
      is associated in an additive fashion with low CD4 cell counts and high plasma and
      cellular HIV viral load.
AB  - We report on a cross-sectional study of virological and immunological surrogate
      markers of HIV infection in 115 patients for whom a determination of the pol 215
      and pol 41 zidovudine (ZDV) resistance mutations had been described between
      January 1995 and February 1996. The patients received ZDV alone or a combination
      of ZDV and zalcitabine or didanosine. A total of 55, 15 and 45 patients exhibited
      a wild (W), a mixed (MIX) or a mutant (M) genotype at codon pol 215,
      respectively; 85, 10 and 20 patients exhibited a W, a MIX or a M genotype at
      codon pol 41, respectively. Patients exhibiting the pol 215 M genotype had lower
      CD4 cells, higher plasma viral load and higher proviral burden than patients
      exhibiting the pol 215 W genotype. Patients who had variants exhibiting both pol
      215 M and pol 41 M or MIX genotypes had significantly worsened surrogate marker
      values than patients having variants only carrying the pol 215 M genotype. These
      observations demonstrate that the two mutations additively associate with
      pejorative surrogate markers.

PMID- 9754950
TI  - Antiviral activity of Viracea against acyclovir susceptible and acyclovir
      resistant strains of herpes simplex virus.
AB  - Viracea, a topical microbicide, is a blend of benzalkonium chloride and
      phytochemicals derived from Echinacea purpurea and is a proprietary formula from
      Destiny BioMediX Corp. Viracea was tested against 40 strains of herpes simplex
      virus (HSV): 15 strains (five HSV-1 and ten HSV-2) were resistant to acyclovir
      (ACV-R) and 25 strains (13 HSV-1 and 12 HSV-2) were susceptible to ACV (ACV-S).
      The median ED50 of Viracea for the five ACV-R strains of HSV-1 was a 1:100
      dilution of the drug with a range of 1:50-1:400. The median ED50 of Viracea for
      the ten ACV-R strains of HSV-2 was 1:200 with a range of 1:50-1:3200. For the ACV
      S strains of HSV-1 and HSV-2, the median ED50 of Viracea was 1:100 and 1:200,
      respectively. The cytotoxicity of Viracea was evaluated in a standard neutral red
      dye uptake assay in human foreskin fibroblasts. The cytotoxicity of Viracea
      approached only 50% at the highest concentration of the drug tested, a 1:2
      dilution, indicating that Viracea is non-toxic in this cell cytotoxicity assay.
      Although the active component(s) in Viracea that has anti-HSV activity is not
      known, it appears that this extract has good antiviral activity against both ACV
      resistant and ACV susceptible strains of HSV-1 and HSV-2.

PMID- 9754951
TI  - Plectin in the human central nervous system: predominant expression at pia/glia
      and endothelia/glia interfaces.
AB  - Plectin is a high molecular weight protein that serves as a versatile
      cytoskeletal cross-linker molecule. Mutations of the human plectin gene have
      recently been identified to cause the autosomal recessive disorder epidermolysis
      bullosa simplex with muscular dystrophy (EBS-MD). A subgroup of EBS-MD patients
      display signs of a neurodegenerative disorder suggesting that the expression of
      defective plectin may also interfere with the structural and functional integrity
      of the human central nervous system. However, the expression pattern of plectin
      in the human brain is still unknown. We therefore analyzed the
      immunohistochemical distribution of plectin in normal hippocampal specimens
      obtained at autopsy and in neocortical and hippocampal tissue of patients who had
      undergone epilepsy surgery. In general, plectin-immunoreactive cells were
      identified as capillary endothelia and astrocytes. A striking feature seen in all
      specimens was the accentuated plectin immunoreactivity of astrocytic end feet
      abutting on blood vessels and on the pial surface. Furthermore, the analysis of
      hippocampal tissue of epilepsy patients with Ammon's horn sclerosis (AHS)
      revealed a strong plectin labeling of reactive astrocytes. The latter finding
      suggests that the up-regulation of plectin, which parallels the increase of glial
      fibrillary acidic protein, may be a general feature of reactive astroglia. The
      predominant expression of plectin at pia/glia and endothelia/glia interfaces in
      the human brain indicates that plectin may have an integral role in the
      structural organization of the blood-brain barrier and the leptomeninges.

PMID- 9754952
TI  - Argyrophilic grain disease is associated with apolipoprotein E epsilon 2 allele.
AB  - Argyrophilic grain disease (AGD) is a distinct degenerative disorder of the human
      brain associated with the formation of abnormally phosphorylated tau protein. AGD
      related cytoskeletal changes are known to affect specific subsets of nerve cells
      and oligodendrocytes. Here we demonstrate a remarkable association between the
      apolipoprotein E (ApoE) epsilon2 allele and AGD. Individuals afflicted with AGD
      (n = 48) reveal a significantly higher frequency of the epsilon2 allele compared
      with controls (n = 43) (22% versus 4%, P < 0.0002). The association between AGD
      and epsilon2 allele of ApoE suggests that AGD can be distinguished from other
      neurodegenerative disorders not only neuropathologically, but also genetically.

PMID- 9754953
TI  - Apolipoprotein E allele frequencies in argyrophilic grain disease.
AB  - Apolipoprotein E (ApoE) genotypes were analyzed in 35 subjects with argyrophilic
      grain diseases (AgD). Neuropathologically, all cases were characterized by
      abundant argyrophilic grains in the hippocampus and in the entorhinal or
      parahippocampal cortex. We found an ApoE epsilon4 allele frequency of 0.007 in
      AgD patients, which is significantly different from the epsilon4 allele
      frequencies reported in age-matched Alzheimer's disease (AD) patients (0.24), but
      not from age-matched controls (0.09). We conclude that the ApoE epsilon4 allele
      does not constitute a risk factor for the development of AgD. Our results further
      suggest that AgD is a progressive disorder differentiated from AD by
      morphological and genetic criteria.

PMID- 9754954
TI  - Fiber-type-dependent expression of adenovirus-mediated transgene in mouse
      skeletal muscle fibers.
AB  - We show the efficient transduction and expression of the lacZ gene in the
      skeletal muscle of adult C57BL/10ScSn mice after adenovirus-mediated gene
      transfer. Of the myofibers in the tibialis anterior muscle 62% were beta
      galactosidase positive after injection of the lacZ gene under the control of the
      chicken beta-actin promoter and the cytomegalovirus enhancer. The transduced gene
      was preferentially expressed in type IIA and IIX fibers, which were richer in
      oxidative enzymes than type IIB fibers.

PMID- 9754955
TI  - Bcl-2, Bax and Bcl-x expression in neuronal apoptosis: a study of mutant weaver
      and lurcher mice.
AB  - We investigated the expression of the apoptosis modulating proteins Bcl-2, Bax
      and Bcl-x in the cerebellum of mutant lurcher and weaver mice. Lurcher Purkinje
      cells and weaver germinal (granule neuron progenitor) cells both die via
      apoptosis during the postnatal cerebellar development. No significant changes in
      the expression patterns were detected prior to the actual cell death process.
      Instead apoptotic lurcher Purkinje cells exhibited increased Bax and Bcl-x
      expression, while surviving cells had an expression pattern similar to that of
      healthy littermates. Increased Bax expression was also found in apoptotic weaver
      germinal cells, while no change of Bcl-x expression was detected. Bcl-2 was
      expressed at low levels in cerebellar neurons and no loss of Bcl-2 was evident.
      The observed expression patterns of Bcl-2, Bax and Bcl-x protein in apoptotic
      lurcher and weaver neurons support the hypothesis that the execution of neuronal
      apoptosis involves increased expression of Bax, which could represent a general
      mechanism in diverse neurodegenerative processes.

PMID- 9754956
TI  - Murine cytomegalovirus induces apoptosis in non-infected cells of the developing
      mouse brain and blocks apoptosis in primary neuronal culture.
AB  - Cytomegalovirus (CMV) is the most common cause of congenital infection, resulting
      in birth defects such as microcephaly. In this study, we found that apoptosis is
      induced in the developing mouse brain infected with murine cytomegalovirus (MCMV)
      in an association with neuronal cell loss. With the combination of the terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) technique
      and immunohistochemical staining, 3.8% of the TUNEL-positive cells were double
      stained with the antibody to neuron-specific enolase, while none of the TUNEL
      positive cells were stained with antibodies to the immediate early and early
      viral antigens of MCMV. Furthermore, distribution pattern of the TUNEL-positive
      cells was different from that of viral DNA-positive cells detected by the in situ
      DNA-DNA hybridization. More than 30% of the TUNEL-positive cells were double
      stained with the F4/80 antibody specific for microglia/macrophages, which were
      sometimes swollen, presumably the consequence of engulfment of the neuronal
      apoptotic cells. In the primary neuronal cultures, MCMV infection inhibited the
      induction of apoptosis either by serum deprivation or by glutamate treatment. It
      was also confirmed by the double-staining method that apoptosis was not induced
      in the viral-infected neuronal cultures. These results suggest that MCMV
      infection induces apoptosis in non-infected neuronal cells, presumably by
      indirect mechanisms, and that apoptotic cells are engulfed by
      microglia/macrophages. The induction and blocking of neuronal apoptosis by viral
      infection may be important for morphological and functional brain disorders in
      the congenital CMV infection.

PMID- 9754957
TI  - Astrocytic pathology in progressive supranuclear palsy: significance for
      neuropathological diagnosis.
AB  - Progressive supranuclear palsy (PSP) is known to have tau-positive cytoskeletal
      abnormalities in astrocytes and oligodendroglia as well as neurons. Astrocytic
      tau-positive structures (tuft-shaped astrocytes; Tu-SA) were studied to elucidate
      their proper significance in the neuropathological diagnosis of PSP. The
      distribution and incidence of Tu-SA were examined in 26 cases of PSP. The disease
      specificity of Tu-SA was demonstrated by comparison with diseases accompanied by
      neurofibrillary tangles (NFTs) and those with or without cytoskeletal
      abnormalities other than NFTs. In PSP, Tu-SA appeared prominently in the
      precentral and premotor cortex (areas 4 and 6) of the superior and middle frontal
      gyri, but were quite scare in the temporal lobe and limbic area. In the
      subcortical nuclei, they appeared preferentially in the putamen and were also
      scattered in other degenerating regions. In the cerebrum the Tu-SA and NFTs were
      distributed in quite different regions. The assessment of the incidence of Tu-SA
      in area 6 revealed that only 5 of 26 PSP cases lacked Tu-SA in the examined
      fields. In contrast, in the control diseases, Tu-SA were found only rarely in
      cases of corticobasal degeneration in the cerebral cortex among other frequent
      tau-positive structures. One case of Pick's disease showed occasional Tu-SA but
      only in the hippocampal region and not in the frontal lobe or putamen. In
      summary, although the absence of Tu-SA does not necessarily exclude the
      possibility of PSP, Tu-SA in the frontal lobe and putamen is highly suggestive
      for PSP. Thus, detection of Tu-SA and the ranking of the characteristic
      distribution of NFTs contribute to the neuropathological diagnosis of PSP.

PMID- 9754958
TI  - Presenile Alzheimer dementia characterized by amyloid angiopathy and large
      amyloid core type senile plaques in the APP 692Ala-->Gly mutation.
AB  - Mutations at codons 717 and 670/671 in the amyloid precursor protein (APP) are
      rare genetic causes of familial Alzheimer's disease (AD). A mutation at codon 693
      of APP has also been described as the genetic defect in hereditary cerebral
      hemorrhage with amyloidosis of the Dutch type (HCHWA-D). We have reported a
      APP692Ala-->Gly (Flemish) mutation as a cause of intracerebral hemorrhage and
      presenile dementia diagnosed as probable AD in a Dutch family. We now describe
      the post-mortem examination of two demented patients with the APP692 mutation.
      The neuropathological findings support the diagnosis of AD. Leptomeningial and
      parenchymal vessels showed extensive deposition of Abeta amyloid protein.
      Numerous senile plaques consisted of large Abeta amyloid cores, often measuring
      more than 30 microm in diameter and were surrounded by a fine meshwork of
      dystrophic neurites. In addition, there were a large number of paired helical
      filaments in pyramidal neurons and dystrophic neurites. Our findings show that
      the APP692 mutation leads to morphological abnormalities that are similar to AD,
      but the morphology of senile plaques is clearly distinct from that described in
      sporadic and chromosome 14-linked AD patients, in patients with APP717 mutations
      causing familial, presenile AD and in patients with the APP693 mutation causing
      HCHWA-D.

PMID- 9754959
TI  - Ultrastructural and permeability features of microvessels in the olfactory bulbs
      of SAM mice.
AB  - The ultrastructural features of microvessels showing increased permeability to
      intravenously injected horseradish peroxidase (HRP) were examined in the
      olfactory bulbs of senescence-accelerated prone mice (SAMP8), which showed age
      related deficits in learning and memory, and senescence-accelerated resistant
      mice (SAMR1), which did not show the age-related deficits. HRP was visualized
      with tetramethyl benzidine (TMB) and diaminobenzidine (DAB) for light and
      electron microscopic examination, respectively. In the olfactory bulbs of 13
      month-old SAMP8 mice, the staining reaction with TMB for HRP appeared in the
      neuropil of central area (granule cell layer and subependymal layer), in the pia
      mater and in the vascular wall. Some vessels located in the central area showed
      several changes observed at the ultrastructural level. The cytoplasm of the
      endothelial cells, especially in the arterioles, was segmentally thickened and
      contained numerous vesicles and vacuoles, some of which were HRP positive. The
      endothelial cell surface was occasionally undulated with microvillous
      protrusions. Membranous inclusions within the basal lamina, suggesting the
      cellular (presumably pericytal) degeneration, were frequently observed,
      especially in venules. The collagen deposits were occasionally observed in the
      subendothelial space of some vessels. Perivascular cells with vacuolated
      inclusions or lipid-like droplets were present around some vessels in the central
      area of the olfactory bulbs of aged SAMP8 mice. On the other hand, in the
      microvessels located in the areas negative for HRP-TMB reaction, except the
      vessel walls, the cytoplasm of the endothelial cells with smooth luminal surface
      was flattened and some vesicles located there contained HRP-DAB reaction product.
      Weak staining reaction with TMB for HRP appeared also in the central area of the
      olfactory bulbs of 3-month-old SAMP8 mice and 3- and 13-month-old SAMR1 mice. The
      cytoplasm of the endothelial cells in the olfactory bulbs of these mice was
      focally thickened and contained some cytoplasmic vesicles. Occasionally, the
      endothelial cell surface was moderately undulated with few microvillous
      protrusions. Membranous inclusions within the basal lamina were not observed in
      these animals. These findings indicate that the endothelial cells and pericytes
      in some vessels located in the central area of the olfactory bulb of aged SAMP8
      mice, which show staining reaction with TMB for HRP, are ultrastructurally
      changed, suggesting their altered functions.

PMID- 9754960
TI  - Reappraisal of progressive multifocal leukoencephalopathy due to simian virus 40.
AB  - Several cases of progressive multifocal leukoencephalopathy (PML) have been
      associated with simian virus 40 (SV40), rather than with JC virus (JCV), the
      polyomavirus originally isolated from PML tissue. PML has, therefore, been
      defined as a demyelinating syndrome with possible multiple viral etiologies.
      Tissues from three of the cases thought to be associated with SV40 were available
      for reexamination. Monoclonal antibodies specific for SV40 capsid antigen VPI,
      virus-specific biotinylated DNA probes for in situ hybridization, and virus
      specific primers in the polymerase chain reaction (PCR) were used. Macaque PML
      brain served as a positive control tissue for SV40 brain infection. Monoclonal
      antibodies to SV40 VPI failed to recognize viral antigen in lesions from all
      three human PML cases. The biotinylated DNA probe, which reacted with SV40 in
      macaque PML, failed to detect SV40 in human PML. However, JCV could be detected
      by in situ hybridization with a JCV-specific DNA probe. Moreover, JCV DNA
      sequences were amplified by PCR from the human PML tissues, whereas SV40 DNA
      sequences were amplified only from the macaque brain. Thus, we could not confirm
      the original reports that the demyelinating agent in these three cases of PML was
      SV40, rather than JCV. We conclude that SV40 infection of the central nervous
      system need not be ruled out in the differential diagnosis of PML.

PMID- 9754961
TI  - Mitochondrial dysfunction induced by oxidative stress in the brains of hamsters
      infected with the 263 K scrapie agent.
AB  - Scrapie, one of the prion diseases, is a transmissible neurodegenerative disease
      of sheep and other animals. Clinical symptoms of prion diseases are characterized
      by a long latent period, followed by progressive ataxia, tremor, and death. To
      study the induction of neurodegeneration during scrapie infection, we have
      analyzed the activities of various antioxidant enzymes and mitochondrial enzymes
      in cerebral cortex, brain stem, and cerebellum of scrapie-infected hamsters. The
      activity of mitochondrial Mn-superoxide dismutase (SOD) was decreased, while the
      activities of cytosolic Cu/Zn-SOD and catalase were not altered in infected
      brains. The activities of glutathione peroxidase and glutathione reductase were
      increased in scrapie-infected hamsters. The decreased activity of Mn-SOD might
      result in increasing oxidative stress in the mitochondria of infected brain; this
      concept is supported by our findings of a high level of lipid peroxidation, and
      low levels of ATPase and cytochrome c oxidase activity in the infected cerebral
      mitochondria. In addition, structural abnormalities of mitochondria have been
      observed in the neurons of hippocampus and cerebral cortex of infected brain.
      These results suggest that mitochondrial dysfunction caused by oxidative stress
      gives rise to neurodegeneration in prion disease.

PMID- 9754962
TI  - Complement C1-inhibitor expression in Alzheimer's disease.
AB  - In situ and in vitro studies suggest that activation of locally produced
      complement factors may act as a mediator between amyloid deposits and
      neurodegenerative changes seen in Alzheimer's disease (AD). C1-esterase inhibitor
      (C1-Inh), which regulates activation of C1 of the complement classical pathway,
      can be detected immunohistochemically in its inactivated form in activated
      astrocytes and dystrophic neurites in AD plaque areas. In this study, designed to
      investigate the cellular source of C1-Inh, C1-Inh was found to be secreted in a
      functionally active form by astrocytes cultured from postmortem human brain
      specimens as well as by neuroblastoma cell lines. Recombinant human interferon
      gamma (IFN-gamma), which stimulates C1-Inh synthesis in various cell types,
      several-fold stimulated C1-Inh protein secretion by cultured human astrocytes
      derived from different regions of the central nervous system and by one (SK-N-SH)
      of two neuroblastoma cell lines (SK-N-SH and IMR-32) included in this study. In
      contrast to IFN-gamma, other cytokines [interleukin (IL)-1beta, IL-6 and tumor
      necrosis factor (TNF)-alpha] that can be found in brain areas affected by AD, did
      not stimulate C1-Inh secretion by astrocytes or neuroblastomas in vitro. This
      inability to secrete C1-Inh is probably due to unresponsiveness at the
      transcriptional level, since C1-Inh secretion paralleled the expression of the
      2.1-kb C1-Inh mRNA. In situ hybridization with a C1-Inh RNA antisense probe
      labeled neurons rather than astrocytes, suggesting a role for neurons as
      producers of complement regulatory proteins in vivo. Since IFN-gamma is
      apparently lacking in the brain parenchyma, and amyloid plaque-associated
      cytokines (IL-1beta, IL-6, TNF-alpha) do not stimulate C1-Inh expression in
      vitro, the nature of the stimulus responsible for neuronal C1-Inh expression in
      AD brains remains to be investigated.

PMID- 9754963
TI  - Polyneuropathy with endoneurial immune complex deposition as the first
      manifestation of systemic lupus erythematosus.
AB  - A 72-year-old male presented with progressive sensorimotor polyneuropathy. Later
      weight loss, proteinuria and deteriorating renal function were noted. The
      electrophysiological examinations revealed extensive, symmetrical demyelinating
      and axonal polyneuropathy. Frozen sections obtained from sural nerve biopsy
      sample showed the presence of immune complexes and complements in the walls of
      the epi- and endoneurial blood vessels, and perineurium suggestive of systemic
      lupus erythematous (SLE). IgG and Clq deposits were also present along the
      basement membranes of Schwann cells. The electron microscopy confirmed the
      presence of immune complex deposition. Diagnosis of SLE was proven by positive
      serology (anti-nuclear antibodies, anti-Sm, anti-RNP, anti-double-stranded DNA)
      and renal biopsy showing membranous lupus nephritis with extensive immune complex
      deposition in the tubular basement membranes. Despite combined immunosuppressive
      treatment for 10 months, the patient died of complications of generalized immune
      complex vasculitis. The manifestation of SLE in elderly patients, especially in
      males, is very rare. Moreover, the polyneuropathy is an unusual initial symptom
      of SLE. Immune complex deposition in Schwann cell basement membrane probably
      plays an important role in the pathomechanism of sensorimotor polyneuropathy in
      SLE.

PMID- 9754964
TI  - Retroperitoneal ectopic neural mass: "abdominal brain"--presentation of two cases
      and proposal of classification of paraneuraxial neural ectopia.
AB  - An encapsulated mass of brain tissue was found in the retroperitoneum of a fetus
      of gestational week 15 and a boy of age 3 years. The masses possessed fibrous
      tissue that bound them to the spine and intraspinal connective tissue,
      respectively, but there was no evidence of direct continuity of the ectopic brain
      tissue with the normal central nervous system. There was no dysraphism. In our
      fetal case, possible Foix-Alajouanine anomaly was additionally found. The ectopic
      neural tissue in the retroperitoneal region may be termed "abdominal brain." In
      the literature, an identical state has been described in the head (paracranial
      region) but there are no other records of the paraspinal region. Despite the
      different locations of the masses (head/paracranial or
      retroperitoneum/paraspinal), these ectopic brain masses should belong to the same
      disorder spectrum of the paraneuraxial neural ectopia, a new concept.

PMID- 9754965
TI  - Beta-galactosidase deficiency in a Korat cat: a new form of feline GM1
      gangliosidosis.
AB  - A 7-month-old Korat cat was referred for a slowly progressive neurological
      disease. Circulating monocytes and lymphocytes showed the presence of single or
      multiple empty vacuoles and blood leukocytes enzyme assay revealed a very low
      beta-galactosidase activity level (4.7 nmol/mg per h) as compared to unaffected
      parents and relatives. Histologically, the cat, euthanized at the owner request
      at 21 months of age, presented diffuse vacuolization and enlargement of neurons
      throughout the brain, spinal cord and peripheral ganglia, severe cerebellar
      neuronal cell loss, and moderate astrocytosis. Stored material was stained with
      periodic acid-Schiff on frozen sections and with the lectins Ricinus conmmunis
      agglutinin-I, concanavalin A and wheat germ agglutinin on paraffin-embedded
      sections. Ultrastructurally, neuronal vacuoles were filled with concentrically
      whorled lamellae and small membrane-bound vesicles. In the affected cat, beta
      galactosidase activity was markedly reduced in brain (18.9%) and liver (33.25%),
      while total beta-hexosaminidase activity showed a remarkable increase.
      Quantitation of total gangliosides revealed a 3-fold increase in brain and 1.7
      fold in liver of affected cat. High-performance thin layer chromatography (HPTLC)
      detected a striking increase of GM1-ganglioside. On densitometric analysis of
      HPTLC bands, the absorption of GM1-ganglioside band was 98.52% of all stained
      bands (GD1a, GD1b, GT1b). Based on clinical onset, morphological and
      histochemical features, and biochemical findings, the Korat cat GM1
      gangliosidosis is comparable with the human type II (juvenile) form. However,
      clinical progression, survival time and level of beta-galactosidase deficiency do
      not completely fit with those of human type II GM1-gangliosidosis. The disease in
      the Korat cat is also different from other reported forms of feline GM1
      gangliosidosis.

PMID- 9754966
TI  - Relationship between mechanomyogram signals and changes in force of human
      forefinger flexor muscles during voluntary contraction.
AB  - In previous studies on mechanomyogram (MMG) signals no analysis of these signals
      accompanying force generation has been performed. Therefore, we have recorded MMG
      signals (previously referred to as muscle sound or acoustomyographic signals)
      during voluntary contractions of forefinger flexor muscles in 31 young subjects.
      These subjects made contractions to produce force records of triangular or
      trapeziform shape. The peak target force amounted to 10, 20 or 40 N which
      represented less than 40% of maximal voluntary contraction. The MMG signals
      during the transient phases of force generation at three different rates were
      analysed. The MMG intensity level calculated for MMG records and the peak-to-peak
      amplitude of MMG signals correlated with both the velocity of force increase and
      the contraction force. The occurrence of the strongest MMG signals corresponded
      to changes in contractile force. Therefore, it is suggested that measurements of
      these parameters could be a useful tool in studies of changes in contractile
      force.

PMID- 9754967
TI  - Mechanomyogram from the different heads of the quadriceps muscle during
      incremental knee extension.
AB  - To investigate the time- and frequency-domain responses of mechanomyograms (MMGs)
      during the progressive fatigue induced by intermittent incremental contractions,
      a surface MMG was obtained from the three muscle heads of the quadriceps muscle
      in seven subjects while they performed isometric knee extensions lasting 7.6 min.
      Isometric intermittent incremental contractions started at 1% of the maximal
      voluntary contraction (MVC) for 3 s, with a 3-s relaxation period in between each
      contraction, and the contraction level was increased by 1% of MVC for every
      contraction (by 10% of MVC per min) up to exhaustion. Separate contractions with
      sufficient rest periods were also conducted to serve for the MMG characteristics
      without fatigue. The integrated MMG (iMMG) was linearly related to force in all
      of the muscles when fatigue was not involved. With regard to the incremental
      contractions, the relationship exhibited an ascending-descending shape, but the
      behavior was not the same for the individual muscle heads, especially for the
      rectus femoris muscle. A steep increase in the median frequency of MMG from
      around 60% of MVC corresponded to a decrease in iMMG. These results suggest that
      analysis of MMG in the time- and frequency-domain during an incremental protocol
      is a useful way of characterizing the motor unit recruitment strategy and fatigue
      properties of individual muscles.

PMID- 9754968
TI  - Regional blood flow in conscious rats after head-down suspension.
AB  - Exposure to microgravity in humans causes cardiovascular deconditioning affecting
      blood pressure, heart rate and vascular responsiveness. This study investigated
      cardiac output, arterial blood pressure and regional blood flows [radioactive
      microspheres: 57Co, 15.5 (SEM 0.1) microm in diameter] in conscious and freely
      moving rats subjected to 14 days of simulated microgravity (head-down suspension,
      HDS) in male Wistar rats: control (horizontally attached, n = 7), suspended for
      14 days (n = 8) and suspended/allowed to recover for 10 min (R10min, n = 5) or 24
      h (n = 9). Compared to the control group, 14 days of HDS resulted in reduced
      total peripheral resistance (37%); an increased cardiac index (65%) was
      associated with no significant change in the mean arterial pressure BPa. There
      were elevated brain (63%), visceral (> 20%), hindlimb (> 80%) and forelimb (>
      215%) muscle blood flows. In the R10min group, the BPa decreased (18%) and the
      regional blood flows returned to control values. Within 24 h the BPa as well as
      cardiac index and total peripheral resistance were restored. In conclusion, 14
      days of HDS engendered local circulatory changes resulting in transient blood
      pressure instability during recovery.

PMID- 9754969
TI  - Influence of bright light exposure for several hours during the daytime on
      cutaneous vasodilatation and local sweating induced by an exercise heat load.
AB  - The aim of the present study was to investigate the effect of exposure to
      differing light intensities for several hours during the daytime on the cutaneous
      vasodilatation and local forearm sweat rate induced by exercise. Seven healthy
      female subjects were exposed to bright light of 6000 lux (bright) or dim light of
      100 lux (dim) during the daytime between 0900 hours to 1330 hours, followed by
      exposure to 150 lux until the test was over at 1600 hours. They spent their time
      in neutral conditions (29 degrees C, 40% relative humidity) from 0900 hours to
      1500 hours, and then exercised on a cycle ergometer for 30 min at 50% maximal
      physical work capacity. Average tympanic temperatures were significantly lower in
      bright than in dim from 1133 hours to 1430 hours. The onset of cutaneous
      vasodilatation and local forearm sweating occurred at significantly lower
      tympanic temperature (Tty) during exercise after bright than after dim. After
      exercise, the cessation of forearm sweating and the rapid change of skin blood
      flow occurred at significantly lower Tty after bright than after dim. It was
      concluded that exposure to bright light over several hours during the daytime
      could reduce Tty and shift the threshold Tty for cutaneous vasodilatation and
      forearm sweating to a lower level.

PMID- 9754970
TI  - Energy and substrate metabolism during a 42-day bed-rest in a head-down tilt
      position in humans.
AB  - Microgravity-induced changes in body composition (decrease in muscle mass and
      increase in fat mass) and energy metabolism were studied in seven healthy male
      subjects during a 42-day bed-rest in a head-down tilt (HDT) position. Resting
      energy expenditure (REE), fat and glucose oxidation were estimated by indirect
      calorimetry on days 0, +8 and +40 of the HDT period. Assessments were performed
      both in post-absorptive conditions and following two identical test meals given
      at 3-h intervals. Body composition (dual x-ray absorptiometry) was measured on
      days 0, +27, +42. Mean post-absorptive lipid oxidation decreased from 53 (SEM 8)
      mg x min(-1) (day 0) to 32 (SEM 10) mg x min(-1) (day 8, P = 0.04) and 36 (SEM 8)
      mg x min(-1) (day 40, P = 0.06). Mean post-absorptive glucose oxidation rose from
      126 (SEM 15) mg x min(-1) (day 0) to 164 (SEM 14) mg x min(-1) (day 8, P = 0.04)
      and 160 (SEM 20) mg x min(-1) (day 40, P = 0.07). Mean fat-free mass (FFM)
      decreased between days 0 and 42 [58.0 (SEM 1.8) kg and 55.3 (SEM 1.7) kg, P <
      0.01] while fat mass increased without reaching statistical significance. The
      mean REE decreased from 1688 (SEM 50) kcal x day(-1) to 1589 (SEM 42) kcal x day(
      1) (P = 0.056). Changes in REE were accounted for by changes in FFM. Mean energy
      intake decreased from 2532 (SEM 43) kcal x day(-1) to 2237 (SEM 50) kcal x day(
      1) (day 40, P < 0.01) with only a minor decrease in the proportion of fat. We
      concluded that changes in fat oxidation at the whole body level can be found
      during HDT experiments. These changes were related to the decrease in FFM and
      could have promoted positive fat balance hence an increase in fat mass.

PMID- 9754971
TI  - Electromyogram as an indicator of neuromuscular fatigue during incremental
      exercise.
AB  - This study analysed the changes in the electromyographic activity (EMG) of the
      vastus lateralis muscle (VL) during an incremental maximal oxygen uptake test on
      a treadmill. A breakpoint in the integrated electromyogram (iEMG)-velocity
      relationship has already been interpreted in two ways: either as a sign of
      neuromuscular fatigue or as an expression of the iEMG-velocity relationship
      characteristics. The aim of this study was to test a method of distinguishing
      fatigue effects from those due to increases in exercise power. Eight well-trained
      male runners took part in the study. They completed a running protocol consisting
      of 4-min stages of increments in power output. Between each stage (about 15 s
      after the start of a minute at rest), the subjects had to maintain a standard
      effort: a 10-s isometric leg extension contraction [50% isometric maximal
      voluntary contraction (IMVC)]. The EMG was recorded during the running and
      isometric protocols, a change in the EMG signal during the isometric exercise
      being considered as the sign of fatigue. The iEMG-velocity relationships were
      strongly fitted by a second-order polynomial function for data taken at both the
      start (r = 0.98) and the end (r = 0.98) of the stage. Based on the stability of
      the 50%IMVC-iEMG relationship noted between stages, the start-iEMG has been
      identified as expressing the iEMG-velocity relationship without fatigue. The
      stage after which end-iEMG increased significantly more steeply than start-iEMG
      was considered as the iEMG threshold and was simultaneous with the ventilatory
      equivalent for carbon dioxide threshold. The parallel changes of minute
      ventilation and iEMG would suggest the existence of common regulation stimuli
      linked either to effort intensity and/or to metabolic conditions. The fall in
      intracellular [K+] has been discussed as being one of the main factors in
      regulating ventilation.

PMID- 9754972
TI  - A comparison of physiological responses and rating of perceived exertion between
      high-impact and low-impact aerobic dance sessions.
AB  - The aim of this study was to compare the exercise intensity and rating of
      perceived exertion (RPE) of a high-impact (HIP) and a low-impact (LIP) university
      aerobic dance session. Ten women [mean (SD) age 22.9 (2.6) years] took part in
      the study. An incremental treadmill test was performed by each subject to
      determine maximum oxygen consumption (VO2max) and maximum heart rate (HRmax). The
      measured VO2max [mean (SD)] was 49.0 (7.5) ml x kg(-1) x min(-1). The subjects
      were randomly assigned to LIP and HIP sessions (i.e. five of the subjects
      participated in the HIP session first, and the other five participated in the LIP
      session first). In a laboratory, heart rate, oxygen uptake and RPE were measured
      throughout each session for each subject. Expired air was collected continuously
      throughout the sessions using Douglas bags (ten bags over a 30-min period). The
      sessions consisted of 20 min of aerobic exercise (bags 1-7) followed by 5 min of
      local muscular endurance exercise (bags 8 and 9) and 5 min of flexibility
      exercises (bag 10). The mean intensity of the aerobic section of the LIP and HIP
      sessions was 51.6% and 64.7% VO2max, respectively. Ninety-five percent confidence
      intervals for the average difference between the HIP and LIP sessions demonstrate
      that the %VO2max was between 12% and 14% higher for the HIP session. The mean
      %HRmax for the LIP and HIP sessions was 71.4% and 76.7%, respectively, with the
      %HRmax in the HIP session being between 5.4% and 7.2% higher on average than that
      of the LIP session. On average, the RPE for the aerobic section of the HIP
      session (12.1) was consistently higher than that of the LIP session (11.1). HIP
      activity has the potential to maintain/improve the aerobic fitness of its
      participants. According to the literature, the exercise intensity elicited by LIP
      activity may have a limited training effect for the population utilised in this
      study, and for some individuals may result in detraining. Conversely, LIP
      activities may be an appropriate mode of exercise for overweight and unfit
      individuals.

PMID- 9754973
TI  - Transient oxygen uptake response to exercise characterizes functional capacity of
      the cardiocirculatory system in patients with chronic heart failure: a random
      stimulus approach.
AB  - The transient response of oxygen uptake (VO2) to submaximal exercise, known to be
      abnormal in patients with cardiovascular disorders, can be useful in assessing
      the functional status of the cardiocirculatory system, however, a method for
      evaluating it accurately has not yet been established. As an alternative approach
      to the conventional test at constant exercise intensity, we applied a random
      stimulus technique that has been shown to provide relatively noise immune
      responses of system being investigated. In 27 patients with heart failure and 24
      age-matched control subjects, we imposed cycle exercise at 50 W intermittently
      according to a pseudo-random binary (exercise-rest) sequence, while measuring
      breath-by-breath VO2. After determining the transfer function relating exercise
      intensity (W) to VO2 and attenuating the high frequency ranges (> 6 exercise-rest
      cycles x min(-1)), we computed the high resolution band-limited (0-6 cycles x
      min(-1)) VO2 response (0-120 s) to a hypothetical step exercise. The VO2 response
      showed a longer time constant in the patients than in the control subjects [47
      (SD 37) and 31 (SD 8) s, respectively, P < 0.05]. Furthermore, the amplitude of
      the VO2 response after the initial response was shown to be significantly smaller
      in the patients than in the control subjects [176 (SD 50) and 267 (SD 54) ml x
      min(-1) at 120 s]. The average amplitude over 120 s correlated well with peak VO2
      (r = 0.73) and deltaVO2/deltaW (r = 0.70), both of which are well-established
      indexes of exercise tolerance. The data indicated that our band-limited VO2 step
      response using random exercise was more markedly attenuated and delayed in the
      patients with heart failure than in the normal controls and that it could be
      useful in quantifying the overall functional status of the cardiocirculatory
      system.

PMID- 9754974
TI  - Effect of increasing running velocity on electroencephalogram in a field test.
AB  - This study was designed to measure the electroencephalogram (EEG) after exercise
      with increasing intensity. In a field test with increments in running velocity a
      2-min EEG was recorded, together with blood lactate concentration and heart rate,
      after each stage. An individual protocol was used, with up to six stages of
      running to ensure comparability of exercise intensity among the subjects, in each
      of 19 athletes (17 men, 2 women) experienced in leisure-time running. The
      exercise consisted initially of three running stages of aerobic exercise
      intensity without blood lactate accumulation followed by stages with an increase
      of lactate concentration. The protocol of the field test led to a progressive
      increase in cortical activity directly after the stages without blood lactate
      accumulation mainly in the delta frequency band, followed by theta and alpha-1
      frequency band, and less pronounced in the alpha-2 and in the beta frequency
      bands. After the stages with an onset and further increase of blood lactate
      accumulation significant decreases in the beta-2, beta-1 and alpha-1 frequency
      bands occurred predominantly in temporal (T3, T4, T5, and T6) and occipital (O1,
      and O2) electrode positions, indicating a stage-by-stage decrease of activity.
      This decrease may be explained by feed-back from working muscle, via afferents to
      the cortex from intero- and proprio-receptors and affective processes. This could
      suggest that through a higher running intensity indicated by an onset of blood
      lactate accumulation metabolic and mechanical changes led to alterations within
      the afferent systems influencing the level of cortical activity.

PMID- 9754975
TI  - Dynamic calibration of mechanically, air- and electromagnetically braked cycle
      ergometers.
AB  - In this study we measured the accuracy of the following types of cycle ergometer
      against the criterion of a dynamic calibration rig (DCR): 35 friction-braked
      (Monark), 5 research-grade air-braked (Repco) and 5 electromagnetically braked (2
      Siemens, 1 Elema-Schonander, 1 Ergoline, 1 Warren E. Collins). Monark ergometer
      power outputs over the range 58.9-353.2 W significantly (P < 0.001)
      underestimated those registered by the DCR with mean accuracies of 91.7-97.8%.
      The least accurate individual reading for each of the six up-scale (0-353.2 W)
      power outputs ranged from 81.6 to 91.6%; corresponding down-scale (353.2-0 W)
      accuracies were 85.1-92.5%. A hysteresis effect was furthermore evident for this
      ergometer in that up-scale measurements were significantly (P < 0.05) greater
      than down-scale ones. In addition, when the oldest [mean (SD): 11.3 (2.3) years
      old] and newest [1.4 (0.8) years old] eight ergometers were compared, the latter
      were significantly (P < 0.05) more accurate over the range 117.7-294.3 W. Apart
      from the two lowest power outputs of 47 W (62.2-96.0% accuracy) and 127 W (88.0
      97.7% accuracy), the individual up-scale and down-scale accuracies of the Repco
      ergometers ranged from 98.0 to 104.2% for power outputs of 272.7-1137.8 W and the
      means were not significantly different from those of the DCR. There was also no
      evidence of hysteresis. Except for the initial power output of 50 W (40 rev/min:
      83.8-99.2% accuracy; 60 rev/min: 93.2-122.6% accuracy), the individual accuracies
      of the electromagnetically braked ergometers ranged from 89.3 to 101.4% over the
      up-scale range of 100-400 W, and none of the means were significantly different
      from those of the DCR. The variability of individual errors for the preceding
      data emphasises that all cycle ergometers should be validated against the
      criterion of a DCR if accurate power outputs are required.

PMID- 9754976
TI  - Brain temperature and limits on transcranial cooling in humans: quantitative
      modeling results.
AB  - Selective brain cooling (SBC) of varying strengths has been demonstrated in a
      number of mammals and appears to play a role in systemic thermoregulation.
      Although primates lack obvious specialization for SBC, the possibility of brain
      cooling in humans has been debated for many years. This paper reports on the use
      of mathematical modeling to explore whether surface cooling can control
      effectively the temperature of the human cerebrum. The brain was modeled as a
      hemisphere with a volume of 1.33 1 and overlying layers of cerebrospinal fluid,
      skull, and scalp. Each component was assigned appropriate dimensions, physical
      properties and physiological characteristics that were determined from the
      literature. The effects of blood flow and of thermal conduction were modeled
      using the steady-state form of the bio-heat equation. Input parameters included
      core (arterial) temperature: normal (37 degrees C) or hyperthermic (40 degrees
      C), air temperature: warm (30 degrees C) or hot (40 degrees C), and sweat
      evaporation rate: 0, 0.25, or 0.50 l x m(-2) x h(-1). The resulting skin
      temperatures of the model ranged from 31.8 degrees C to 40.2 degrees C, values
      which are consistent with data obtained from the literature. Cerebral
      temperatures were generally insensitive to surface conditions (air temperature
      and evaporation rate), which affected only the most superficial level of the
      cerebrum (< or =1.5 mm) The remaining parenchymal temperatures were 0.2-0.3
      degrees C above arterial temperatures, regardless of surface conditions. This
      held true even for the worst-case conditions combining core hyperthermia in a hot
      environment with zero evaporative cooling. Modeling showed that the low surface
      to-volume ratio, low tissue conductivity, and high rate of cerebral perfusion
      combine to minimize the potential impact of surface cooling, whether by
      transcranial venous flow or by conduction through intervening layers to the skin
      or mucosal surfaces. The dense capillary network in the brain assures that its
      temperature closely follows arterial temperature and is controlled through
      systemic thermoregulation independent of head surface temperature. A review of
      the literature reveals several independent lines of evidence which support these
      findings and indicate the absence of functionally significant transcranial venous
      flow in either direction. Given the fact that humans sometimes work under
      conditions which produce face and scalp temperatures that are above core
      temperature, a transcranial thermal link would not necessarily protect the brain,
      but might instead increase its vulnerability to environmentally induced thermal
      injury.

PMID- 9754977
TI  - Implications of moderate altitude training for sea-level endurance in elite
      distance runners.
AB  - Elite distance runners participated in one of two studies designed to investigate
      the effects of moderate altitude training (inspiratory partial pressure of oxygen
      approximately 115-125 mmHg) on submaximal, maximal and supramaximal exercise
      performance following return to sea-level. Study 1 (New Mexico, USA) involved 14
      subjects who were assigned to a 4-week altitude training camp (1500-2000 m)
      whilst 9 performance-matched subjects continued with an identical training
      programme at sea-level (CON). Ten EXP subjects who trained at 1640 m and 19 CON
      subjects also participated in study 2 (Krugersdorp, South Africa). Selected
      metabolic and cardiorespiratory parameters were determined with the subjects at
      rest and during exercise 21 days prior to (PRE) and 10 and 20 days following
      their return to sea-level (POST). Whole blood lactate decreased by 23% (P < 0.05
      vs PRE) during submaximal exercise in the EXP group only after 20 days at sea
      level (study 1). However, the lactate threshold and other measures of running
      economy remained unchanged. Similarly, supramaximal performance during a
      standardised track session did not change. Study 2 demonstrated that hypoxia per
      se did not alter performance. In contrast, in the EXP group supramaximal running
      velocity decreased by 2% (P < 0.05) after 20 days at sea-level. Both studies were
      characterised by a 50% increase in the frequency of upper respiratory and
      gastrointestinal tract infections during the altitude sojourns, and two male
      subjects were diagnosed with infectious mononucleosis following their return to
      sea-level (study 1). Group mean plasma glutamine concentrations at rest decreased
      by 19% or 143 (74) microM (P < 0.001) after 3 weeks at altitude, which may have
      been implicated in the increased incidence of infectious illness.

PMID- 9754978
TI  - Detection of the change point in oxygen uptake during an incremental exercise
      test using recursive residuals: relationship to the plasma lactate accumulation
      and blood acid base balance.
AB  - The purpose of this study was to develop a method to determine the power output
      at which oxygen uptake (VO2) during an incremental exercise test begins to rise
      non-linearly. A group of 26 healthy non-smoking men [mean age 22.1 (SD 1.4)
      years, body mass 73.6 (SD 7.4) kg, height 179.4 (SD 7.5) cm, maximal oxygen
      uptake (VO2max) 3.726 (SD 0.363) l x min(-1)], experienced in laboratory tests,
      were the subjects in this study. They performed an incremental exercise test on a
      cycle ergometer at a pedalling rate of 70 rev x min(-1). The test started at a
      power output of 30 W, followed by increases amounting to 30 W every 3 min. At 5
      min prior to the first exercise intensity, at the end of each stage of exercise
      protocol, blood samples (1 ml each) were taken from an antecubital vein. The
      samples were analysed for plasma lactate concentration [La]pl, partial pressure
      of O2 and CO2 and hydrogen ion concentration [H+]b. The lactate threshold (LT) in
      this study was defined as the highest power output above which [La-]pl showed a
      sustained increase of more than 0.5 mmol x l(-1) x step(-1). The VO2 was measured
      breath-by-breath. In the analysis of the change point (CP) of VO2 during the
      incremental exercise test, a two-phase model was assumed for the 3rd-min-data of
      each step of the test: Xi = at(i) + b + epsilon(i) for i = 1,2, ..., T, and E(Xi)
      > at(i) + b for i = T + 1, ..., n, where X1, ..., Xn are independent and
      epsilon(i) approximately N(0, sigma2). In the first phase, a linear relationship
      between VO2 and power output was assumed, whereas in the second phase an
      additional increase in VO2 above the values expected from the linear model was
      allowed. The power output at which the first phase ended was called the change
      point in oxygen uptake (CP-VO2). The identification of the model consisted of two
      steps: testing for the existence of CP and estimating its location. Both
      procedures were based on suitably normalised recursive residuals. We showed that
      in 25 out of 26 subjects it was possible to determine the CP-VO2 as described in
      our model. The power output at CP-VO2 amounted to 136.8 (SD 31.3) W. It was only
      11 W -- non significantly -- higher than the power output corresponding to LT.
      The VO2 at CP-VO2 amounted to 1.828 (SD 0.356) l x min(-1) was [48.9 (SD 7.9)%
      VO2max]. The [La-]pl at CP-VO2, amounting to 2.57 (SD 0.69) mmol x l(-1) was
      significantly elevated (P < 0.01) above the resting level [1.85 (SD 0.46) mmol x
      l(-1)], however the [H+]b at CP-VO2 amounting to 45.1 (SD 3.0) nmol x l(-1), was
      not significantly different from the values at rest which amounted to 44.14 (SD
      2.79) nmol x l(-1). An increase of power output of 30 W above CP-VO2 was
      accompanied by a significant increase in [H+]b above the resting level (P =
      0.03).

PMID- 9754979
TI  - Concomitant inhaled corticosteroid resensitises cardiac beta2-adrenoceptors in
      the presence of long-acting beta2-agonist therapy.
AB  - OBJECTIVE: The aim of the present study was to evaluate the effects of
      concomitant inhaled corticosteroid therapy on the sensitivity of cardiac beta2
      adrenoceptors in patients receiving regular long-acting beta2-agonists. METHODS:
      Twelve healthy subjects (6 female), mean age 29 years, were randomised in a
      double-blind cross-over study to receive either inhaled placebo or inhaled
      budesonide 1.2 mg twice daily, each for 7 days, with a minimum of 7 days washout
      period between the two treatments. Patients also received concomitant treatment
      with inhaled eformoterol 24 microg twice daily during each of the 2 treatment
      periods. The patients attended the laboratory during both treatment periods at
      0730 hours, when a dose-response curve for systemic beta2-adrenoceptor responses
      to inhaled salbutamol (0.8-3.2 mg) was constructed before and after completing 7
      days of each treatment. Early morning (0800 hours) plasma cortisol was also
      evaluated as a marker of systemic glucocorticoid activity. RESULTS: There was a
      significant fall in 0800 hours plasma cortisol induced by budesonide comparing
      pre- and post-values (407 vs 322 nmol.1(-1), but not with placebo. There were no
      differences in the response to salbutamol prior to treatment when comparing
      eformoterol with placebo versus eformoterol with budesonide. Comparing before and
      after within-treatment heart rate response, there was a significant reduction in
      peak salbutamol response with eformoterol and placebo, which was partially
      reversed by eformoterol and budesonide. For between-treatment comparisons after
      eformoterol treatment, the heart rate was significantly higher in the presence of
      budesonide in comparison with placebo for peak salbutamol response (change from
      baseline), i.e. 24.2 vs 34.7 beats min(-l). There was, however, no significant
      difference in the peak delta potassium response to salbutamol after eformoterol
      treatment when comparing budesonide with placebo (-0.39 vs -0.48 mmol.1(-1)).
      CONCLUSION: Concomitant therapy with inhaled budesonide resensitised the cardiac
      beta2-adrenoceptor response to salbutamol in subjects who were receiving regular
      twice-daily eformoterol. This may be of clinical relevance in terms of the
      propensity for systemic beta2-mediated adverse effects with repeated puffs of
      salbutamol, which might conceivably occur in the setting of acute asthma.

PMID- 9754980
TI  - The effect of nimesulide versus placebo on hemostasis in healthy volunteers.
AB  - OBJECTIVE: The primary objective was to evaluate the effect of 7 days treatment
      with nimesulide on bleeding time. Blood coagulation, von Willebrand factor and
      platelet aggregation ex vivo were investigated as a secondary objective. METHOD:
      A randomised, double-blind, placebo-controlled, parallel group, single centre
      study performed on 20 healthy male volunteers who received either placebo or
      nimesulide 100 mg twice daily for 7 days. Bleeding time, platelet count and
      platelet aggregation, thromboplastin time (prothrombin time), activated partial
      thromboplastin time, fibrinogen, Factor VIII:C, vWF:Ag, vWF:RCof and platelet
      rich plasma aggregation following stimulation with adenosine 5'-diphosphate,
      collagen, arachidonic acid, ristocetin, thrombin and thrombin receptor-activating
      peptide were measured at baseline (day 0), and then 3 h after the first (day 1)
      and last (day 7) treatment. RESULTS: The bleeding times for all subjects remained
      within the normal range throughout the study period, with no significant
      differences between the two treatment groups. There were no significant changes
      from baseline in platelet aggregation studies or in any of the other haemostasis
      tests, with no significant differences between the two groups. No clinically
      significant adverse events were reported or observed. CONCLUSIONS: Daily
      administration of 200 mg nimesulide for 7 days neither prolongs bleeding time nor
      modifies any of the other haemostasis variables measured. The lack of
      interactions with important haemostatic mechanisms suggests that nimesulide may
      also be used in patients with bleeding problems. This expectation has still to be
      confirmed by clinical experience.

PMID- 9754981
TI  - Aqueous humour concentration and the intraocular pressure-lowering effect of
      topical betaxolol before cataract surgery.
AB  - OBJECTIVE: The aim was to study the relationship between aqueous humour betaxolol
      concentration and intraocular pressure (IOP). METHODS: In this double-blind,
      randomized study, we administered betaxolol (a) or placebo (b) ocularly to 131
      patients scheduled for cataract surgery. The patients were randomly divided into
      ten groups. In groups 1a and 1b, the drug was scheduled to be instilled 1-2 h, in
      groups 2a and 2b 12 h, in groups 3a and 3b 24 h, and in groups 4a and 4b 48 h
      before surgery. The pupil was dilated in all eyes prior to surgery. The IOP was
      measured with Perkins' applanation tonometer before the instillation of the drug
      and just before the peribulbar block. Twenty microlitres of 0.5% betaxolol or
      placebo solution was instilled into the eye. IOP was also measured before
      instillation of the drug and after 1 2 h in undilated eyes of 20 patients, whose
      contralateral eye was to be operated on, to rule out the effect of pupil dilation
      on IOP (groups 5a and 5b). Aqueous humour betaxolol concentrations were analysed
      using a radioreceptor assay. RESULTS: Betaxolol did not decrease IOP
      significantly in eyes with pupillary dilation. Both betaxolol and placebo
      decreased IOP significantly in patients without pupillary dilation, the effect of
      betaxolol being slightly more pronounced. The betaxolol concentration in aqueous
      humour was 731 ng m-1 in group la, 2.4 h after drug instillation. Measurable
      concentrations of betaxolol were also detected in aqueous humour in group 4a 47.7
      h after drug administration. CONCLUSION: No correlation between aqueous humour
      concentration of betaxolol and the effect on IOP was found in eyes where the
      pupil was dilated before surgery. A single betaxolol dose did not decrease IOP
      significantly in patients undergoing cataract surgery, but the IOP decreasing
      effect was, however, clearly seen in patients who did not receive mydriatic
      drugs. The routine use of topical betaxolol prior to cataract surgery to decrease
      IOP is not recommended.

PMID- 9754982
TI  - Ketorolac use in outpatients and gastrointestinal hospitalization: a comparison
      with other non-steroidal anti-inflammatory drugs in Italy.
AB  - OBJECTIVE: To compare the risk of hospitalization for gastroduodenal ulcer
      associated with the use of ketorolac and other non-steroidal anti-inflammatory
      drugs (NSAIDs). METHODS: A cohort and a nested case-control study were carried
      out. All residents in the region of Umbria (Italy), aged 35-84 years, who had
      been given at least one NSAID prescription in 1993 and 1994 were identified.
      Exposure to drugs was ascertained through a drug prescription database. We
      estimated rate ratios of hospitalization for gastroduodenal ulcer with or without
      complications in the current, recent or past period according to exposure to
      different NSAIDs. RESULTS: Rate ratio estimates, adjusted for age and sex, were
      2.8 for any current NSAID and 1.4 for any recent NSAID. The highest rate ratios
      of lesions of any severity for current NSAID use were observed for piroxicam (RR:
      4.6) and ketorolac (RR: 3.4). For gastrointestinal haemorrhage or perforation the
      highest rate ratios were those for ketorolac (RR: 5.9) and piroxicam (RR: 4.8).
      Rate ratio estimates did not change after adjustment for concomitant use of
      gastrotoxic drugs, use of gastroprotective agents not associated with NSAIDs and
      prior use of NSAIDs. CONCLUSION: Our study demonstrates the need to adhere to the
      restrictions relating to the indications and duration of use of ketorolac. At
      present piroxicam represents a greater public health concern since it is
      confirmed to be among the most gastrotoxic NSAIDs and is one of the most commonly
      prescribed NSAIDs in Italy.

PMID- 9754983
TI  - Lack of drug-drug interaction between three different non-steroidal anti
      inflammatory drugs and omeprazole.
AB  - OBJECTIVE: To study, in three separate investigations, the potential interaction
      between omeprazole and three different non-steroidal anti-inflammatory drugs
      (NSAIDs; diclofenac, naproxen and piroxicam) in healthy male and female subjects.
      METHODS: Each investigation was an open, randomized, three-way cross-over study,
      in which the subjects were given omeprazole 20 mg once daily for 1 week, the
      NSAID in therapeutic daily doses (diclofenac 50 mg bid, naproxen 250 mg bid, or
      piroxicam 10 mg om), or a combination of omeprazole and each NSAID. The plasma
      concentrations of the NSAID as well as of omeprazole were determined on the last
      day of each investigation period. RESULTS: None of the NSAIDs studied had any
      effect on the plasma concentration versus time curve (AUC) of omeprazole. It was
      also demonstrated that omeprazole 20 mg daily had no significant influence on the
      pharmacokinetics of the NSAIDs. The AUC ratio, (NSAID +omeprazole):NSAID alone,
      was 1.11, 0.99, and 0.99 for diclofenac, naproxen, and piroxicam, respectively.
      CONCLUSION: Diclofenac, naproxen, and piroxicam can be administered together with
      omeprazole 20 mg daily without need for dosage alteration. There was no
      significant change in the bioavailability of theses NSAIDs during omeprazole
      therapy in this study.

PMID- 9754984
TI  - Safety and pharmacokinetics of a single oral dose of amisulpride in healthy
      elderly volunteers.
AB  - OBJECTIVE: Amisulpride is a substituted benzamide neuroleptic, which binds
      selectively to dopamine D2 and D3 receptors, mainly in the limbic structures.
      States of delusion and agitation occur frequently in the population aged more
      than 65 years, especially in demented patients and this sometimes requires the
      use of neuroleptics. The objectives of this study were to determine the safety
      and the pharmacokinetic profile of 50 mg of amisulpride administered orally as a
      single dose to elderly volunteers. METHODS: Twenty healthy volunteers (10 men and
      10 women) aged 65 79 years were included in this open trial. Frequent
      measurements of blood pressure and heart rate were made and ECG and blood samples
      were performed up to 72 h after drug intake. RESULTS: The overall clinical and
      cardiovascular safety was satisfactory. The mean Cmax of the racemate amisulpride
      in elderly people was 64.1+/-6.7 ng ml(-1), and was not different from the value
      of 56+/-4.1 ng ml(-1) in young subjects. As with the Cmax, the mean values of
      t1/2 and AUC in elderly people (15.6+/-1.3 h and 667+/-51 ng. ml(-1).h,
      respectively) were not different to values observed in young subject
      (respectively 11.7+/-0.5 h and 603+/-25 ng m1(-1) h). CONCLUSION: A single oral
      dose of amisulpride was well tolerated and showed a similar pharmacokinetic
      profile in healthy elderly and young subjects. However, these findings should be
      confirmed after multiple dosing in a larger population in order to establish the
      lack of need of dosage adjustment in this elderly population.

PMID- 9754985
TI  - Comparative pharmacokinetic study of oral and rectal formulations of artesunic
      acid in healthy volunteers.
AB  - OBJECTIVE: A single cross-over, comparative pharmacokinetic study of oral and
      rectal formulations of 200 mg artesunic acid in 12 healthy Malaysian volunteers
      is reported. METHODS: Plasma concentrations of artesunic acid and
      dihydroartemisinin were determined simultaneously by HPLC with electrochemical
      detection. The test drug was well tolerated and no undesirable adverse effects
      were observed. RESULTS: Comparison of pharmacokinetic parameters of artesunic
      acid after oral and rectal administration showed statistically significant
      differences in t(max) and AUC, with no changes for Cmax and t1/2. As for
      dihydroartemisinin, differences were observed for t(max) and Cmax but not for
      AUC. CONCLUSION: There appear to be pharmacokinetic differences between oral and
      rectal modes of administration. The significance of these findings should be
      explored in malaria patients before appropriate therapeutic regimens are devised.

PMID- 9754986
TI  - Pharmacokinetics of nimustine, methotrexate, and cytosine arabinoside during
      cerebrospinal fluid perfusion chemotherapy in patients with disseminated brain
      tumors.
AB  - OBJECTIVE: This study was conducted to evaluate the pharmacokinetics of
      anticancer drugs in cerebrospinal fluid (CSF) perfusion chemotherapy. METHODS: We
      administered CSF perfusion chemotherapy with nimustine (ACNU), methotrexate
      (MTX), and cytosine arabinoside (Ara-C) to three patients with disseminated
      malignant brain disease. The drugs were infused via Ommaya's reservoirs to the
      lateral ventricle and removed by drainage from the temporal lobe or lumbar spine.
      CSF and plasma concentrations of the anticancer drugs were determined by high
      performance liquid chromatography and fluorescence polarization immunoassay.
      RESULTS: The concentrations of anticancer drugs in the discharged CSF peaked
      about 40 min after the start of a 1-h CSF perfusion. After the perfusion, the
      drug level in CSF decreased exponentially in a monophasic manner. ACNU and Ara-C
      were not detectable in the discharged CSF in the temporal lobe at 6 h and 48 h
      after perfusion, respectively, but MTX was detectable at 48 h. The maximum
      concentration ratio of anticancer drugs and the duration of perfusion were
      inversely correlated. The plasma concentrations of anticancer drugs were much
      lower than those in CSF. The half-life of ACNU was very short (0.2-1.1 h),
      whereas the half-lives of MTX and Ara-C were relatively long (2.81-13.5 h and
      1.84 6.25 h, respectively). The half-lives of the anticancer drugs in CSF tended
      to decrease with repeated CSF perfusion chemotherapy. CONCLUSION: Results suggest
      that CSF perfusion chemotherapy enables a high concentration of anticancer drug
      to be administered for dissemination in the spinal cord within a short period of
      time, with minimal adverse effects.

PMID- 9754987
TI  - Zolpidem 10 mg given at daytime is not antagonized by 300 mg caffeine in man.
AB  - OBJECTIVE: Caffeine counteracts various effects of traditional benzodiazepines
      (BZDs). As zolpidem, a short-acting hypnotic, is an atypical GABAA-BZD agonist,
      we investigated when caffeine would counteract the effects of zolpidem as well.
      METHODS: In daytime study I, zolpidem 10 mg (capsule) and caffeine 150 or 300 mg
      (in decaffeinated coffee) were given, alone and in combinations, to parallel
      groups (n = 15-17) of healthy students in double-blind and placebo-controlled
      manner. Objective and subjective tests were done before and 45 min and 90 min
      after intake. Ranked delta values (changes from baseline) were analysed by one
      way contrast ANOVA and Scheffe's tests. In daytime study II, four healthy
      subjects took zolpidem 10 mg alone, and together with blinded caffeine 250 mg or
      (at -45 min) erythromycin 750 mg. Objective and subjective effects were measured
      and plasma zolpidem concentrations assayed at baseline and 45 min and 90 min
      after zolpidem intake. RESULTS: In study I, practice effects after placebo (ad +
      30%) were seen for letter cancellation and digit symbol substitution but not for
      flicker fusion tests. Zolpidem alone significantly impaired (P < 0.05 vs delta
      placebo) letter cancellation and digit symbol substitution at 45 min and 90 min,
      lowered the flicker fusion threshold at 45 min, and caused subjective drowsiness,
      mental slowness, clumsiness and feeling of poor performance. Caffeine alone
      showed a non-significant trend to improve objective performance. The combined
      effects of zolpidem and either dose of caffeine matched those measured after
      zolpidem alone. Zolpidem + caffeine 300 mg was not stronger than zolpidem +
      caffeine 150 mg in impairing immediate memory and causing subjective sedation. In
      study II, zolpidem caused objective and subjective sedation; neither caffeine nor
      erythromycin modulated the effects of zolpidem or plasma zolpidem concentrations.
      CONCLUSION: The sedative effects of 10 mg of zolpidem are not antagonized by 150
      300 mg of caffeine in pharmacodynamic or pharmacokinetic terms.

PMID- 9754988
TI  - Genotypes for the cytochrome P450 enzymes CYP2D6 and CYP2C19 in human longevitY.
      Role of CYP2D6 and CYP2C19 in longevity.
AB  - OBJECTIVE: To test whether some genotypes for CYP2D6 or CYP2C19 could contribute
      to longevity, we genotyped 241 Danish nonagenarians and centenarians for CYP2D6
      and CYP2C19. METHODS: For CYP2D6 we identified the alleles CYP2D6*1, CYP2D6*3 and
      CYP2D6*4 with allele-specific polymerase chain reaction (PCR). The CYP2D6*5
      alleles were identified with a long PCR method. For CYP2C19 we identified the
      alleles CYP2C19*1, CYP2C19*2 and CYP2C19*3 with an oligonucleotide ligation
      assay. RESULTS: The four alleles for CYP2D6 did not occur in Hardy-Weinberg
      proportions. The frequency of poor metabolism was slightly higher (10.2%) than
      expected [7.7%; odds ratio (OR) = 1.36 (0.75-2.40)]. The genotypes for CYP2C19
      occur in Hardy-Weinberg proportions. The frequency of poor metabolism (3.8%) was
      not significantly different from a young control group [3.1%; OR = 1.21 (0.26
      5.75)]. CONCLUSION: CYP2D6 could play a role in human longevity due to the lack
      of Hardy-Weinberg proportions. If CYP2D6 only plays a role in longevity by
      protecting the poor metabolizers from cancer, we should expect a rise in the
      frequency in these genotypes in Denmark from 7.7% among young adults to 10-11%
      among very old people. We found a frequency of poor metabolism of 10.2% in the
      very old group. CYP2C19 is - due to the occurrence of Hardy-Weinberg proportions
      and the expected number of poor metabolizers unlikely to contribute to human
      longevity.

PMID- 9754989
TI  - Genetic polymorphism of debrisoquine (CYP2D6) and proguanil (CYP2C19) in South
      Pacific Polynesian populations.
AB  - OBJECTIVE: Genetic oxidation polymorphisms of debrisoquine (CYP2D6) and proguanil
      (CYP2C19) were studied in unrelated healthy South Pacific Polynesian volunteers
      recruited in the South Island of New Zealand. METHODS: Phenotyping for CYP2D6 and
      CYP2C19 activities was determined using debrisoquine and proguanil, respectively,
      as probe drugs by measuring the urinary metabolic ratio of parent drug and its
      metabolite. RESULTS: Of 100 Polynesian subjects phenotyped, the metabolic ratio
      of debrisoquine ranged from 0.01 to 9.94. Therefore, all South Pacific
      Polynesians were classified as extensive metabolizers of debrisoquine according
      to previously established criteria of the antimode. The prevalence of poor
      metabolizers of debrisoquine (CYP2D6) in this Polynesian population is 0% (95%
      confidence interval of 0-3.6%). Oxidation polymorphism of CYP2C19 using proguanil
      as a probe was also studied in 59 Polynesian volunteers. The frequency
      distribution of the proguanil/cycloguanil ratio was bimodal. The
      proguanil/cycloguanil ratios for these subjects ranged from 0.09 to 34.4. Using a
      recommended proguanil/cycloguanil ratio cut-off point of 10 established in
      Caucasian populations, eight Polynesian subjects were identified as poor
      metabolizers of proguanil (CYP2C19), which corresponds to a poor metabolizer
      phenotype frequency of 13.6% (a 95% confidence interval of 5.9-24.6%).
      CONCLUSION: The incidence of poor metabolizer phenotypes for debrisoquine
      (CYP2D6) in South Pacific Polynesians appears to lower than in Caucasian
      populations, while the prevalence of poor metabolizers for proguanil (CYP2C19) in
      this ethnic population is higher. The frequencies of the poor metabolizer
      phenotype for debrisoquine and also for proguanil in South Pacific Polynesians
      are similar to those reported in Asian populations.

PMID- 9754990
TI  - Variability of coumarin 7- and 3-hydroxylation in a Jordanian population is
      suggestive of a functional polymorphism in cytochrome P450 CYP2A6.
AB  - OBJECTIVE: To determine the variability of coumarin 7- and 3-hydroxylation in a
      human population and to evaluate the evidence for the existence of genetic
      polymorphism in these pathways. 7-Hydroxylation of coumarin is considered to be a
      detoxication pathway, whilst 3-hydroxylation, which predominates in rats, leads
      to hepatotoxicity in the rat. Coumarin metabolic phenotypes could aid in refining
      the risk evaluation for humans of dietary and environmental exposure to coumarin
      and for the chronic use of coumarin in high doses as a drug to treat lymphoedema
      and certain cancers. METHODS: Healthy male and female Jordanian volunteers (n =
      103) were administered 2 mg coumarin by mouth and collected their 0-8-h urines.
      These, together with pre-dose blank urines, were analysed by selected-ion
      monitoring gas chromatography mass spectrometry for their content of the coumarin
      metabolites 7-hydroxycoumarin (70HC) and 2-hydroxyphenylacetic acid (2OHPAA), the
      latter arising from the 3-hydroxylation pathway. RESULTS: After coumarin
      administration, excretion of both 70HC and 2OHPAA was highly variable. A coumarin
      metabolic ratio (2OHPAA/7OHC) was suggestive of polymorphism. At least one
      subject had a metabolic response similar to an individual known to be both
      phenotypically and genotypically (CYP2A6 gene) 7-hydroxylation-deficient.
      CONCLUSION: In the light of the finding of high variability and possible
      polymorphism in both the 7- and 3-hydroxylation of coumarin in a human
      population. we recommend a reappraisal of the risk evaluation of human exposure
      to coumarin, particularly in pharmaceutical doses.

PMID- 9754991
TI  - Pharmacokinetics and pharmacodynamics after oral and intravenous administration
      of tolcapone, a novel adjunct to Parkinson's disease therapy.
AB  - OBJECTIVE: To evaluate fully the pharmacokinetics and pharmacodynamics of
      tolcapone, a novel inhibitor of catechol-O-methyltransferase (COMT), after oral
      and intravenous administration. METHODS: Sixteen healthy male volunteers were
      given tolcapone in single doses of 200 mg orally and 50 mg intravenously,
      separated by a washout period of 7 days or more, in a single-center, open-label,
      randomized, cross-over study. Pharmacokinetic parameters were calculated using
      both compartmental and non-compartmental methods; pharmacodynamics were evaluated
      from erythrocyte COMT activity. RESULTS: After an initial lag time of 0.5 h,
      tolcapone was rapidly absorbed (peak plasma concentrations were reached within
      approximately 2 h) following either zero- or first-order absorption kinetics. The
      absolute bioavailability of an oral dose was approximately 60%. The volume of
      distribution was approximately 9 1, and the total clearance was approximately
      71.h-l, resulting in a mean plasma half-life of 1.8 h. The degree of erythrocyte
      COMT inhibition was closely related to tolcapone plasma concentration; a rebound
      in COMT activity was observed after tolcapone withdrawal. Both oral and
      intravenous tolcapone were well tolerated. DISCUSSION: Because of its relatively
      low systemic clearance, tolcapone exhibits only a small degree of first-pass
      metabolism and a relatively good oral bioavailability, which explains the higher
      plasma concentrations and stronger COMT inhibition observed with tolcapone
      compared with entacapone, another COMT inhibitor. The pharmacokinetic and
      pharmacodynamic profile of tolcapone obtained in this study underlines the
      potential of the agent to be used as an adjunct to levodopa in the treatment of
      Parkinson's disease.

PMID- 9754992
TI  - Chronic hypercapnia should not exclude patients from lung volume reduction
      surgery.
AB  - OBJECTIVE: Chronic hypercapnia is still considered to increase the risk for
      perioperative mortality and therefore to be a contraindication for lung volume
      reduction surgery (LVRS). The aim of this study was to analyse the influences of
      hypercapnia upon postoperative outcome. METHODS: The functional improvement
      (preop vs. 3 months postop) and clinical outcome was studied in 22 patients with
      chronic hypercapnia (preoperative arterial pCO2 > or = 45 mmHg) who underwent
      LVRS between 9/94 and 2/97 and were compared to all other patients (n = 58)
      without hypercapnia. Data are expressed as the mean +/- SEM. RESULTS: The 30-day
      mortality was 9.1% (2/22) in patients with chronic hypercapnia (HC) and 5.2%
      (3/58) in patients with normal arterial pCO2 levels (control) (P = n.s). The stay
      on the ICU (3.5 +/- 0.8 vs. 2.1 +/- 0.3 days) and duration of chest drainage (7.3
      +/- 1.2 vs. 7.2 +/- 0.8 days) was similar between both groups (HC vs. control) (P
      = n.s). The preoperative lung function (% of predicted) and blood gas (mmHg)
      parameters were significantly worse in HC patients compared to control patients.
      In both groups significant functional improvements were observed: FeV1 in the
      control group increased by 37% within the first 3 months (29.1 +/- 1.7% of
      predicted vs. 39.9 +/- 3.1% of predicted, P = 0.0198). In the HC group, FeV1
      increased by 73% which was even higher than in the controls (19.5 +/- 1.5% of
      predicted vs. 33.7 +/- 4.7% of predicted, P = 0.0385). All patients of both
      groups who died perioperatively had a significantly higher severity of
      parenchymal destruction than those who survived (P = 0.0277 and 0.0380,
      respectively). CONCLUSIONS: Patients with chronic hypercapnia alone, had no
      significantly higher mortality and morbidity, and therefore should not be
      excluded from LVRS. However, the presence of additional risk factors, such as
      homogeneity of disease, high degree of parenchymal destruction or pulmonary
      hypertension should be considered as contraindications for the procedure.

PMID- 9754993
TI  - Video-assisted thoracoscopic surgery: experience with 341 cases.
AB  - OBJECTIVE: Until recently, thoracoscopy had been used primarily for diagnostic
      purposes for more than 80 years in thoracic diseases. In this report we reviewed
      our video-assisted thoracoscopic surgery experience with 341 cases focusing on
      indications, operative procedures, complications or failure rates. PATIENTS AND
      METHODS: Over the last 3 years, we performed 459 video-assisted thoracoscopic
      procedures. There were 206 male and 135 female patients. RESULTS: The indications
      were diagnostic in 171 cases, and therapeutic in 170 cases. There were no
      operative mortality. Non-fatal complications were seen in 15 cases (4.4%). The
      mean postoperative stay was 5 days. The specific procedures performed were
      operations on the pleura (237 cases), lung (158 cases), mediastinum (56 cases)
      and pericardium (four cases). Conversion to thoracotomy was needed in 43 cases
      (12.6%). Definitive diagnosis was obtained in 100% of patients with pulmonary
      nodule/mass or diffuse lung disease, and 95.2% of patients with undiagnosed
      pleural effusions. The success rate of thoracoscopic approach in non-tuberculous
      thoracic empyema was 87.3%. CONCLUSIONS: Video-assisted thoracoscopic surgery is
      an ideal procedure in the following situations: (1) undiagnosed pleural effusion,
      (2) recurrent pneumothorax or bullous lung disease, (3) stage II thoracic
      empyema, (4) lung cancer staging, (5) peripheral pulmonary nodule, and (6) wedge
      biopsy for diffuse lung disease.

PMID- 9754994
TI  - Is aggressive surgery in pleural empyema justified?
AB  - OBJECTIVE: High risk and a long hospitalization time are often quoted as negative
      aspects of aggressive surgery in pleural empyema. We did a retrospective analysis
      evaluating outcome and duration of hospitalization in patients treated according
      to an aggressive schedule. METHODS: Since 1989 we have treated 101 patients with
      pleural empyema (72 males, 29 females; mean age 50.3 years, range 11-91 years; 77
      metapneumonic empyema, 24 empyema following trauma or abdominal surgery). Sixty
      nine patients had had unsuccessful conservative pre-treatment (antibiotics,
      thorcozentses, drainage/irrigation, VATS). Thirty-one were critically ill
      patients. In eight cases a seropurulent stage of empyema was present, 17 patients
      had fibrinous membranes, 30 an organizing stage with and 46 without well
      identifiable dissection plane. Eighty-five patients proceeded to thoracotomy.
      Pulmonary abscesses or indurative pneumonia necessitated wedge-resection,
      lobectomy, or pneumonectomy in 29 cases. In the presence of gross necroses or
      callosities not amenable to decortication primary open-window thoracostomy (n =
      22) was carried out. In six cases a secondary open-window thoracostomy was
      carried out because of persisting putrid secretion and sepsis persisting after
      decortication or after drainage. The thoracostomy was closed when clean
      granulative tissue developed. Sixteen patients underwent only drainage and
      irrigation because of an early stage or because of a general condition not
      permitting thoracotomy. RESULTS: Three patients died due to severe sepsis not
      responding to treatment, one had fatal bleeding from a duodenal ulcer (mortality
      rate 3.9%). The others were able to resume their preoperative activities. The
      median duration of hospitalization was 14 days (mean 21.1 days; SEM 1.7 days).
      CONCLUSION: Aggressive surgery for pleural empyema beyond the seropurulent stage
      ensures rapid relief from sepsis at a low mortality rate even in very ill
      patients.

PMID- 9754995
TI  - Posptneumonectomy empyema.
AB  - OBJECTIVE: Postpneumonectomy empyema can be managed in many different ways, with
      variable results. In the presence of bronchopleural fistula treatment is much
      more complicated. The results of therapy of postpneumonectomy empyema managed by
      thoracomyoplasty and closure of the bronchial fistula by pedicled muscle flap are
      presented. METHODS: Seven hundred and seventy-eight pneumonectomies had been
      performed for bronchogenic carcinoma. Empyema occurred in 35 (4.5%) cases. There
      were 22 (62.8%) patients with associated bronchopleural fistula. Depending on
      their management, patients were divided into two groups: I: 15 patients managed
      with tube and/or open-window thoracostomy only, II: 20 patients who were treated
      with thoracomyoplasty, which meant the excision of the fibrotic thoracic wall,
      combined with the transposition of the pedicled muscle flap into the empyema.
      There was a need to resect three to four ribs. Eight patients had large
      bronchopleural fistulas. Before thoracomyoplasty was conducted, tube drainage
      ranged from 16 to 120 days (average 46.6 days), the open-window thoracostomy
      ranged from 27 days to 13 years (average 574 days). RESULTS: Only one patient
      from group I was cured, there were five (33.3%) deaths. Nineteen (95.0%) patients
      from group II were successfully cured. Eight large bronchial fistulas were closed
      by suturing the muscle flap into the fistula lumen. The length of hospitalisation
      ranged from 9 to 30 days (median 17.6). The mortality rate in this group was 0%.
      CONCLUSIONS: The excision of the thoracic wall combined with the transposition of
      the pedicled muscle flap is safe and effective in the management of
      postpneumonectomy empyema. Bronchopleural fistulae can be definitely closed by
      suturing the pedicled muscle flap into fistular lumen.

PMID- 9754996
TI  - Pulmonary sequestration: a review of 26 cases.
AB  - OBJECTIVES: Pulmonary sequestration is a continuum of lung anomalies for which no
      single embryonic hypothesis is yet available. The aim of this study was to assess
      the diagnostic tools and treatment for the rare condition, pulmonary
      sequestration, in an unspecialised centre. METHODS: We performed an analysis of
      26 cases of pulmonary sequestration (paediatric and adult) operated at the Centre
      Hospitalier Universitaire Vaudois between May 1959 and May 1997. A review of the
      extralobar and intralobar types of sequestrations is discussed. Angiography is
      compared to other diagnostic tools in this condition, and treatment is discussed.
      RESULTS: Twenty-six cases of pulmonary sequestrations, a rare congenital
      pulmonary malformation, were operated on in the defined time period. Seventy
      three percent (19) of the cases were intralobar and 27% (seven) extralobar.
      Extralobar localisation was basal in 71% and situated between the upper and the
      lower lobe in 29%. In six cases, the diagnosis was made by exploratory
      thoracotomy. In the other 20 cases, diagnosis was evoked on chest X-ray and
      confirmed by angiography. Lobectomy (46%) was the most common treatment
      procedure. Segmental resection was performed in 30% of the cases and bilobectomy
      in 4%. Post-operative morbidity was low. The most significant complications were
      pleural empyema, haemothorax and haemopneumoperitoneum in case of extralobar
      sequestration. There was no evidence of metaplasia or pre-neoplastic changes.
      CONCLUSIONS: Despite its rarity, some radiological features are sufficiently
      suggestive of diagnosis of pulmonary sequestration. Investigations are necessary
      in order to avoid unexpected pathology at the time of operation. Resection of the
      involved lung leads to excellent results and the long-term outcome is highly
      favourable.

PMID- 9754997
TI  - Surgical treatment of echinococcosis by a transthoracic approach: a review of 85
      cases.
AB  - OBJECTIVE: Human echinococcosis remains a serious health problem for the
      Mediterranean countries, among them Greece. As there is no effective medical
      therapy, surgery is still the treatment of choice. MATERIAL AND METHODS: We
      present our experience in the surgical management of hydatidosis by a
      transthoracic approach, based on 85 patients (49 male, 36 female, aged 4-86
      years) treated during 1986-1996. RESULTS: Twenty-one patients (26.3%) appeared
      with complications as: hydatidemesis (n = 5), hydropneumothorax (n = 3), cyst
      infection (n = 3), empyema thoracis (n = 8), cholebronchial (n = 3) and
      cholebronchopleural fistula (n = 1). The location of the cysts was: 61 in the
      lungs (right, 29; left, 24; bilateral, eight), 31 on the liver dome, six in the
      pleural cavity, two in the mediastinum, and one in each of pericardium, chest
      wall, and right pararenal space. Surgical approach involved a thoracotomy or
      median sternotomy in all cases. Pulmonary endocystectomy and capitonnage was the
      procedure of choice in the surgical management. Hepatic cysts were approached
      through a right thoracophrenotomy and were managed with evacuation of the main
      and daughter cysts, suture of the diaphragm to the margins of the cyst, and
      drainage of the cystic and pleural cavities. There was no in-hospital mortality.
      Major postoperative complications were: empyema thoracis (n = 3), biliary fistula
      (n = 2), and bronchopleural fistula (n = 1). Five patients presented later with
      seven recurrences of the disease. CONCLUSION: Transthoracic approach is a good
      and safe choice in surgical treatment of both the intrathoracic and the
      (concomitant or not) hydatid cysts on the upper surface of the liver.

PMID- 9754998
TI  - Clinical experiences with minimally invasive mitral valve surgery using a
      simplified Port Access technique.
AB  - OBJECTIVE: Using the initial experiences with the Port-Access technique for the
      treatment of mitral valve disease some changes were made thus resulting in more
      simple and faster procedures. METHODS: Twenty-nine patients (13 male, 16 female,
      aged 30 to 75 years, median 62.5 +/- 11.0 years) underwent minimally invasive
      mitral valve surgery between May 1996 and December 1997. The underlying diseases
      were: mitral valve insufficiency (n = 16), mitral valve stenosis (n = 7) and
      combined mitral valve disease (n = 6). Through a small right thoracotomy (5-7 cm)
      access to the pericardium and the heart was gained. Cardiopulmonary bypass was
      instituted through femoral cannulation and an intraaortic balloon-catheter was
      introduced for aortic occlusion, aortic root venting and delivery of cold
      crystalloid cardioplegia. Mitral valve repair (five patients) or replacement (24
      patients) was performed. RESULTS: There was no death during the whole follow-up
      period. There was no perivalvular leak and only minor residual mitral valve
      regurgitation was observed on intraoperative or postoperative (3 months)
      transesophageal echocardiography in three patients. There was no postoperative
      study-related complication. Time of ventilation and intensive care unit were
      comparable with the data of patients undergoing conventional mitral valve surgery
      but hospital stay was shorter in the last 10 consecutive cases. CONCLUSIONS: This
      simplified technique of mitral valve surgery combines the advantage of less
      invasive operative and good cosmetic results with the safety of conventional
      mitral valve surgery. At our institution this technique presents in well selected
      patients suffering from mitral valve disease the procedure of choice.

PMID- 9754999
TI  - Aortic valve reconstruction associated to ascending aorta tubular graft
      replacement in aortic incompetence by annuloaortic ectasia.
AB  - OBJECTIVE: Aortic valve incompetence associated with severe aortic ectasia is
      usually treated by aortic valve and ascending aorta replacement. In cases of
      isolated aortic ectasia or in Type A aortic dissection the valve is often normal
      and the incompetence is just due to annular dilatation. Such conditions lead to
      the application of various valve-sparing surgical techniques, as described by
      Senning et al., showing the advantages of preservation of the native valve, but
      the disadvantage of a high technical complexity and a high incidence of
      recidivation. METHODS: We describe a valve-sparing surgical procedure, which has
      the advantage of a direct and simple approach together with satisfying mid-term
      results. After the aortic bulb has been fully transected, the excessive wall
      tissue is resected by two or three triangular excisions just above the valve
      commissures. Wall excision was indicated in those patients with an aortic
      diameter exceeding 65 mm at the sino-tubular junction. Tissue excision should not
      exert tension on to the coronary ostia or excessively reduce aortic diameter.
      Three external Teflon strips, overriding each other, are placed around the aortic
      bulb and are included in the direct suture of the edges of the triangular
      excisions. They are fixed by a running suture over the free border of the bulb.
      Aortic valve commissures are resuspended when needed. In this way, the aortic
      bulb, with a competent valve, is wrapped in a prosthetic and inextensible graft.
      The aortic continuity is then re-established with the interposition of a tubular
      dacron graft. RESULTS: From April 1990 to December 1995, 21 patients (mean age 48
      years, range 32-70) scheduled for surgery for aortic valve incompetence
      associated with annuloaortic ectasia were treated with this technique. In one
      patient the procedure failed to achieve a satisfying valve competence and the
      valve was replaced. In another case a prolapse of the non-coronary cusp required
      reoperation with aortic valve replacement, without further complications. At
      follow-up time (mean 42 months, range 18-78), all patients were well and healthy,
      with control echoes showing no residual valve incompetence and with invariate
      bulb diameters at every successive examination. CONCLUSIONS: Our experience shows
      that this new valve-sparing approach allows safe and persistent correction of
      aortic valve incompetence and annuloaortic ectasia although longer term follow up
      is needed.

PMID- 9755000
TI  - Long-term survivors with pN2 non-small cell lung cancer after a complete
      resection with a systematic mediastinal node dissection.
AB  - OBJECTIVE: A substantial number of surgical patients with pN2 disease have
      survived longer than 5 years without any evidence of recurrence, although the
      surgical indications for those patients remain controversial. The present study
      was performed in order to clarify the clinical characteristics of the long-term
      survivors with pN2 disease. METHODS: We retrospectively reviewed the cases of 111
      patients with pN2 disease who had undergone a complete resection with a
      systematic mediastinal lymph node dissection from 1974 through 1991. RESULTS: Of
      the 111 patients with pN2 disease, 20 survived longer than 5 years after a
      surgical resection. When both the pre- and post-operative conditions were
      compared between the long-term survivors and the others, the long-term survivors
      were characterized by significantly higher proportions of cN0 disease (P =
      0.031), pT1 disease (P = 0.004), skip metastasis without hilar node metastasis (P
      = 0.028), and metastasis of a single mediastinal station (0.044). Of those
      characteristics, only the likelihood of having cN0 disease could be pre
      operatively determined. The survival rate of such a population with cN0-pN2
      disease was 34.5% at 5 years and 29.6% at 10 years after a complete resection,
      respectively. CONCLUSIONS: Pathologic N2 patients with some favorable prognostic
      factors can survive long-term after a complete resection combined with a
      systematic mediastinal lymph node dissection. At present, due to the lack of any
      effective adjuvant therapy, a systematic mediastinal node dissection should be
      routinely performed even in patients with cN0 disease.

PMID- 9755001
TI  - Thirty-day mortality and long-term survival following surgery for prosthetic
      endocarditis: a study from the UK heart valve registry.
AB  - OBJECTIVE: To assess the 30-day mortality, long-term survival and freedom from
      reoperation following surgery for prosthetic endocarditis (PVE). METHOD: A
      retrospective analysis of data from the UK Heart Valve Registry of 322 patients
      who had undergone single mechanical/bioprosthetic valve replacement for PVE
      between 1 January 1986 and 31 December 1996. The mean age was 54.9 +/- 12.8 years
      and 213 (66.1%) were males. There were 170 aortic and 152 mitral valve
      implantations. Eighty-five (26%) of the infected valves were bioprosthetic and
      237 (74%) were mechanical. Of the new prostheses implanted 53 (17%) were
      bioprosthetic and 269 (83%) were mechanical. Of those with infected
      bioprostheses, 50 (15.2%) had mechanical valves at redo surgery, whilst 219
      (68.3%) of infected mechanical prostheses were re-replaced by mechanical
      prostheses. The follow-up was 98% complete with a total of 1084.9 patient years.
      RESULTS: The 30-day mortality was 63 (19.9%; 95%CI 15.9-24.7%). There were 85
      late deaths. One, 5 and 10 year survival rates were 67.1% (61.6-72.0%), 55.0%
      (49.0-60.7%) and 37.6% (27.9-47.2%), respectively. Age was the only significant
      determinant of 30-day mortality (P = 0.04). Age (P = 0.001) and explanting of
      infected bioprosthesis and replacement by mechanical valve (P = 0.04) determined
      long-term survival (P = 0.001). The incidence of re-reoperation was 9.9%. Freedom
      from reoperation for PVE was 88.4, 87.3 and 87.3% at 1, 5 and 10 years,
      respectively. Explanting of bioprosthesis and replacement by mechanical valve (P
      < 0.001) and reoperation within 60 days of native valve replacement (P = 0.02)
      were determinants of reoperation for PVE. Freedom from death or reoperation was
      61.1, 50.6 and 34.2% at 1, 5 and 10 years, respectively. Age (P = 0.003),
      explanting of bioprosthesis and replacement by mechanical valve (P = 0.002) and
      the period between prosthetic re-replacement (P = 0.04) determined freedom from
      death or reoperation. CONCLUSION: Operation for PVE carries a high 30-day
      mortality and reduced long-term survival. There is no evidence that type of
      prosthesis used for re-reoperation determines survival or freedom from re
      reoperation.

PMID- 9755002
TI  - Cardiac surgery with extracorporeal circulation in 23 infants weighing 2500 g or
      less: short and intermediate term outcome.
AB  - OBJECTIVE AND METHODS: From September 1990 to February 1997, 23 consecutive
      critically ill infants (12 males, 11 females) weighing 2500 g or less underwent
      cardiac surgery necessitating extracorporeal circulation (ECC). A retrospective
      study was carried out to evaluate short- and intermediate-term outcome. Mean
      weight at operation was 2265 g (range 1750-2500 g). Mean age at operation was 24
      days. The indications for surgery were transposition of the great arteries (TGA;
      7), ventricular septal defect (VSD; 4), aortic stenosis (AS; 3), univentricular
      heart (UVH; 2), tetralogy of Fallot (TOF; 2), interrupted aortic arch (IAA; 2),
      atrial septal defect (ASD; 1), atrioventicular septal defect (AVSD; 1) and total
      abnormal pulmonary venous return (TAPVR; 1). All patients were in NYHA class IV;
      17 patients (74%) were intubated pre-operatively. RESULTS: The mean aortic cross
      clamping time was 40 min. Twelve patients required deep hypothermia (<20 degrees
      C) with total circulatory arrest (mean duration 19 min). All patients were
      successfully weaned from extracorporeal circulation (ECC). Five patients left the
      operating room with an open sternum (mean duration before closure: 3.5 days).
      Mean duration of artificial ventilation was 10.6 days; of inotropic support 6.7
      days and of intensive care stay 17.8 days. Severe complications were observed in
      19 patients (83%): cardiac failure requiring high inotropic support (13), sepsis
      (7), and acute renal insufficiency (5). One patient needed a ventricular assist
      device. Five patients (22%) died in the intensive care unit (ICU): 2 AS with
      fibroelastosis, 2 IAA with VSD. and 1 UVH with pulmonary atresia. At discharge
      from the ICU, 7 patients were receiving no treatment. Mean duration of follow-up
      was 32 months (range 2-80 months). We had 2 reoperations: 1 for right ventricular
      outflow tract obstruction 1 year after a switch operation and 1 for mitral valve
      replacement 1 year after total abnormal pulmonary venous return repair (death 30
      days post mitral valve replacement). Survival at I year was 73%. At the last
      clinical examination 16 patients were in NYHA class I. CONCLUSION: Despite the
      severity of pre-operative cardiac disease, early surgical repair with ECC in
      infants weighing 2500 g or less is feasible with tolerable mortality yet with
      significant early morbidity.

PMID- 9755003
TI  - Ventriculo-arterial discordance: switching the morphologically left ventricle
      into the systemic circulation after 3 months of age.
AB  - OBJECTIVE: To retrospectively examine a 4 year policy of restoring the
      morphologically left ventricle to the systemic circuit in patients presenting
      after 3 months of age with ventriculo-arterial discordance with or without
      associated atrio-ventricular discordance. This policy was stimulated by the known
      tendency of the morphologically right ventricle to develop dysfunction sooner or
      later when left in the systemic circuit. Such a policy dictates a more complex
      surgical approach and, at this point, it remains controversial whether or not the
      increased surgical complexity is warranted. METHODS: From July 1, 1993 to March
      31, 1997, a total of 29 patients were entered into a protocol for placement of
      the morphologically left ventricle into the systemic circuit. Three groups of
      patients were identified. Group I; congenitally corrected transposition in 14
      patients -- were treated with either a Senning plus arterial switch operation or
      Senning plus Rastelli procedure. Group II; failed atrial switch procedure in 12
      patients of which nine proceeded to arterial switch operation with Senning or
      Mustard takedown and atrial reseptation. Group III; D-transposition of the great
      vessels presenting more than 1 year after birth in three patients who underwent
      arterial switch operation alone. A deconditioned morphologically left ventricle
      required reconditioning by means of preparatory pulmonary artery banding in 17 of
      29 patients. In the patients requiring pulmonary artery banding, an average of
      2.1 pulmonary artery bandings was required to prepare the morphologically left
      ventricle for a systemic pressure workload. RESULTS: In those patients with a
      deconditioned morphologically left ventricle requiring preparatory pulmonary
      artery banding, the mean ratio between the left ventricular and right ventricular
      systolic pressure increased from 0.48 to 0.95. The left ventricular mass
      increased from 46.6 to 81.8 g/m2 in five patients subjected to serial MRI
      measurement. Three patients failed the preparatory pulmonary artery banding and
      did not proceed to anatomical correction. Two subsequently died at a later time.
      In the patients proceeding to complete anatomical correction: group I -- there
      were no early or late deaths. Two patients required pacemaker implantation post
      operatively. Group II -- there were two in-hospital deaths, one early due to
      intrapulmonary hemorrhage and one late, secondary to postoperative left
      ventricular failure with a stormy post-operative course requiring successful ECMO
      placement and weaning. These patients were 18 and 25 years old, respectively. One
      patient proceeded to cardiac transplantation 3 months after surgery due to
      ongoing morphologically left and right ventricular dysfunction. Group III -- all
      patients continue to do well. CONCLUSIONS: Late anatomic correction of ventriculo
      arterial discordance with or without atrio-ventricular discordance can be
      performed at a relatively low risk. Reconditioning of the morphologically left
      ventricle can be achieved by sequential pulmonary banding but is not without
      risk. Failure to achieve adequate reconditioning of the morphologically left
      ventricle by pulmonary artery banding in the older patient probably increases the
      risk of non-survival and may be offset by timely transplantation. Longer follow
      up and an assessment of the functional status of these patients is required to
      assess whether or not this complex surgical approach is indeed warranted.

PMID- 9755004
TI  - Post cardiac surgery phrenic nerve palsy: value of plication and potential for
      recovery.
AB  - OBJECTIVES: Evaluation of an aggressive policy for the treatment of phrenic nerve
      palsy (PNP), following cardiac operations, with emphasis on early diaphragmatic
      plication. Attention was given to the incidence and predisposing factors for PNP
      and the potential for recovery following plication. METHODS: From 1 June 1991 to
      1 January 1996 we prospectively screened patients for PNP following cardiac
      surgery. The diagnosis was suspected if difficulty was experienced in weaning the
      child from the ventilator. If abnormal elevation of the hemidiaphragm was present
      diaphragmatic plication was performed. Echocardiography was used to assess
      subsequent return of diaphragmatic function. RESULTS: Seventeen children (nine
      boys, eight girls), out of 867 (1.9%) children younger than 16 years of age,
      undergoing cardiac operations were found to have PNP. The mean age was 66 days
      (range 1-17 months) with 16 patients below 1 year out of a total of 285 patients
      (incidence 5.6%) and one patient 17 months old. The incidence following open
      procedures was 11/190, following closed procedures 2/95 and following reoperation
      4/83. PNP was diagnosed from 2 to 44 days (mean 14 days) following surgery. It
      was present on the right side in seven cases, the left in nine and was bilateral
      in one patient. Two patients were extubated at the time of diagnosis, one patient
      could be extubated shortly thereafter. Fourteen children underwent diaphragmatic
      plication, at a median 5 days post diagnosis. Extubation was possible 1-60 days
      (mean 4 days) after plication. Mean follow-up was 19 +/- 5 months. Subsequent
      recovery of diaphragmatic movement was documented in seven (41%) children. Time
      to recovery following plication was 16 months, without plication 38 months.
      CONCLUSION: Prospective screening for PNP revealed an incidence in children
      younger than 1 year of 6%. Early plication substantially reduces the duration of
      ventilation, with its associated reduced morbidity and ICU stay.

PMID- 9755005
TI  - Aspartate improves recovery of the recently infarcted rat heart after
      cardioplegic arrest.
AB  - BACKGROUND: We have previously shown that aspartate improves the tolerance of
      normal hearts to cardioplegia. The aim of this study was to investigate whether
      aspartate is also beneficial in the recently infarcted heart. METHODS: Myocardial
      infarction was produced in rats by left coronary artery ligation. Twenty hours
      later their hearts were perfused on an isolated working rat heart apparatus and
      underwent cardioplegic arrest for 30 min at 37 degrees C with or without 20 mM
      aspartate in the cardioplegic solution (n = 11 per group). Functional recovery
      and myocardial high energy phosphate levels were measured at the end of arrest
      and after 30 min of reperfusion. RESULTS: There was no difference in pre-arrest
      pump function between the untreated and aspartate-treated groups. However, after
      reperfusion the aspartate group generated more power (3.4 +/- 0.2 mJ/s per g)
      than the untreated group (2.5 +/- 0.3 mJ/s per g; P < 0.05) such that the
      percentage recovery of pre-arrest power in the aspartate group (67.7 +/- 3.5%)
      was greater than in the untreated group (53.6 +/- 4.9%; P < 0.05). The aspartate
      group also showed increases in aortic flow and myocardial oxygen consumption
      compared to the untreated group (P < 0.05). There were no between-group
      differences in high energy phosphate levels at the end of arrest or after
      reperfusion. CONCLUSION: Aspartate improves functional recovery of the recently
      infarcted heart during cardioplegic arrest, and therefore has potential as a
      useful adjunct to myocardial protection in patients with recent myocardial
      infarction undergoing cardiac surgery.

PMID- 9755006
TI  - Lung transplantation for cystic fibrosis--a single center experience over 8
      years.
AB  - OBJECTIVE: Colonization of the lung and mediastinal lymph nodes with multi
      resistant bacteria, diabetes and malnutrition represent potential risk factors
      for lung transplantation in cystic fibrosis. We therefore reviewed our experience
      in this patient population. METHODS: Between December 1988 and March 1997, 219
      lung and heart-lung transplantations were performed at our institution. Of these,
      39 procedures were done in 35 patients with cystic fibrosis. All candidates (mean
      age 26 years) were oxygen dependent (preoperative mean PO2: 44.8 +/- 9.1 Torr,
      preoperative mean PCO2: 53.4 +/- 10.5 Torr, one patient on respirator). Of the
      primary operations, 34 were performed as bilateral sequential lung transplants,
      one as a heart-lung transplantation. RESULTS: Mean duration on respirator for
      survivors was 3.1 (1-12) days, mean ICU and hospital stay were 4.7 (1-13) and 28
      (12-79) days, respectively. The 3-month mortality rate was 5.7% (two patients
      died due to acute graft failure on days 36 and 73). Other causes of death in the
      follow-up were cerebral bleeding (one patient) and chronic graft failure (three
      patients). The survival rates were 91% at 1 year, 83% at 3 years and 76% at 5
      years. In eight patients, a bronchiolitis obliterans syndrome (BOS) developed (in
      four cases grade 3). The freedom of BOS (grade 1 or more) at 1, 3 and 5 years was
      87, 79 and 55%, respectively. Four retransplantations were performed. Of the 29
      patients alive, only seven are physically limited. CONCLUSION: Bilateral lung
      transplantation for cystic fibrosis allows for acceptable early- and long-term
      results. Postoperative survival is not impaired by infection, diabetes and
      malnutrition. Long-term functional outcome seems to be comparable to lung
      transplantation in patients without infectious pulmonary disease.

PMID- 9755007
TI  - Vascular rejection post heart transplantation is associated with positive flow
      cytometric cross-matching.
AB  - OBJECTIVE: Use of flow cytometry cross-matching for measurement of donor-specific
      alloreactivity and monitoring anti-donor antibodies is well established. This
      study was performed to determine (1) its accuracy as a marker of vascular
      rejection, (2) its correlation with post-transplant outcome and (3) its ability
      to monitor highly sensitized patients requiring antibody removal with plasma
      exchange. METHODS: Serial serum samples from 99 heart transplant recipients were
      examined for the presence of anti-donor antibodies of the IgG class that were
      reactive with T and/or B cryopreserved donor lymphocytes. A sub-group of 20 HLA
      sensitized patients required plasma exchange to remove the anti-HLA antibodies
      and were monitored with flow cytometry cross-matching to assess the degree of
      antibody removal. RESULTS: Positive T-cell reactions were observed in 26 patients
      and positive B-cell reactions in 54. Twenty patients had vascular rejection. A
      significantly larger number of patients with a positive flow cytometry cross
      match had vascular rejection (42% versus 12% for T-cell reactions, and 32% versus
      7% for B-cell reactions; P = 0.002 each). Of the patients who had vascular
      rejection, 11 had a positive T-cell reaction (flow cytometry cross-match
      sensitivity of 55%), and 17 had a positive B-cell reaction (sensitivity of 85%).
      Of the 79 patients who did not develop vascular rejection, 64 had a negative T
      cell reaction (specificity of 81%), and 42 had a negative B-cell reaction
      (specificity of 53%). The actuarial 2-year survival estimates were significantly
      higher in patients with negative T-cell reactions (90% versus 75%; P = 0.04), and
      B-cell reactions (95% versus 78%; P = 0.02). In the highly sensitized subgroup (n
      = 20) the effectiveness of plasma exchange to decrease anti-HLA antibody
      reactivity was a strong predictor of outcome. For patients in whom plasma
      exchange (PE) reduced anti-donor reactivity, 1-year survival was 87% compared to
      25% in those whom PE did not reduce the level of antibody binding as assessed
      with flow cytometry cross-matching (P < 0.0001). CONCLUSIONS: Flow cytometry
      cross-matching provides a valuable marker for the detection of vascular rejection
      after cardiac transplantation. Quantitative measurements may allow evaluation of
      the efficacy of treatment modalities employed in the management of vascular
      rejection in an attempt to improve outcome.

PMID- 9755008
TI  - Reduced renal failure following thoracoabdominal aortic aneurysm repair by
      selective perfusion.
AB  - OBJECTIVES: Renal failure and visceral ischemia are feared complications
      following thoracoabdominal aortic aneurysm (TAAA) repair, significantly
      contributing to mortality. This prospective study describes volume- and pressure
      controlled perfusion of the renal and visceral arteries during TAAA surgery.
      METHODS: In 73 consecutive patients (mean age 59 years), TAAA repair (27 type I,
      28 type II, 8 type III and 10 type IV) was performed, using retrograde and
      selective organ perfusion. Sixteen patients had impaired renal function with
      blood creatinine higher than 100 mmol/l. During the thoracic part of the
      procedure, the mean distal aortic pressure was kept above 60 mm Hg by means of
      left-heart bypass. After opening the abdominal aorta, the renal and visceral
      arteries were individually perfused by means of perfusion catheters (9 French) in
      the first 33 patients (group I). Volume flow through each catheter was assessed
      with ultrasound flow meters and maintained at least at 60 ml/min. In addition to
      volume flow measurements, catheters with pressure sensors were used in the last
      40 patients (group II), allowing pressure-controlled selective perfusion. The
      extent of the aneurysm was comparable in both groups. RESULTS: Mean cross-clamp
      time for the thoracic part was 46 min, including proximal anastomosis and
      reattachment of intercostal arteries. Mean cross-clamp time for the abdominal
      part was 74 min, including re-implantation of intestinal and renal arteries and
      selective dacron grafts to the celiac-axis arteries (n = 5), superior mesenteric
      arteries (n = 8) and renal arteries (n = 25), through which the catheters
      guaranteed continuous perfusion during the time the anastomosis was performed.
      Urine output was uninterrupted in all patients, irrespective of cross-clamp time.
      In group I, one patient (3%) developed renal failure and three patients (9%)
      required temporary peritoneal dialysis. In group II, no patients developed renal
      failure and two patients (5%) required temporary peritoneal dialysis. Thirteen
      patients with pre-existing renal impairment did not deteriorate. No patients
      developed visceral ischemia or multiple-organ failure. Total in-hospital
      mortality was 6/73 (8%) and was related to cardiopulmonary complications.
      CONCLUSIONS: Renal and visceral ischemia can be reduced significantly by
      continuous perfusion during cross-clamping in TAAA repair. Not only sufficient
      volume flow but also adequate arterial pressure appears to be essential in
      maintaining renal function.

PMID- 9755009
TI  - The conventionally ventilated operating theatre and air contamination control
      during cardiac surgery--bacteriological and particulate matter control garment
      options for low level contamination.
AB  - OBJECTIVE: The purpose of the study was to compare the usefulness of a
      conventional bacteriological technique with that of particle counting under lower
      air contamination and better aseptic conditions achieved with special staff
      garments and covering for the patient. Contamination levels were estimated with
      continuous on line air particle counting measurement, volumetric intermittent
      short period aerobic bacteriological cultures and wound surface contact cultures.
      METHODS: In a series of 66 consecutive coronary artery bypass operations
      performed by the same team and in the same theatre using different types of
      patient and staff clothing, the impact of a reduced bacteriological and
      particulate contamination were assessed. The volumetric air contamination of
      particles > or =5 microm and bacteria-carrying particles were monitored 30 cm
      above the sternal wound. The bacterial contamination and bacterial wound
      infections in the sternal and leg wounds were assessed as well. RESULTS: With the
      alternative garment and textile system, the air counts fell from 25 colony
      forming units (CFU)/m3 to 7 CFU/m3 (P < 0.0038). The contamination of the sternal
      wound was reduced by 46% and that of the leg wound by >90%. In order to give
      continuous contamination feedback during the whole operation to the theatre
      staff, particle counts > or =5 microm were monitored and visualized. Air particle
      counts decreased rapidly from 850 particles/m3 and stabilized to approximately 50
      particles/m3 when the alternative clothing system was used (P < 0.001). Low
      particle counts > or =5 microm should offer the possibility to indirectly
      estimate air bacteria carrying particle counts during the entire operation. Less
      than 20% of the total count in this size group carries bacteria. The low air
      contamination was achieved even in an ordinary ventilated theatre when individual
      team members used clean air suits in combination with impermeable patient drapes.
      When air particle level < or =50 particles/m3 is reached, the bacterial air
      contamination is in the order of that of orthopaedic hip operations. The staff
      must during the entire operation adjust their activity to air asepsis.
      CONCLUSIONS: The use of clean air suits and impermeable patient clothing results
      in a low exogenous contamination of air and wound. Continuous air particle
      monitoring is a good intraoperative method to monitor the air contamination
      longitudinally in an operating theatre.

PMID- 9755010
TI  - A case of giant benign localized fibrous tumor of the pleura.
AB  - A 60-year-old man had noted exertional dyspnea and left anterior chest pain. A
      chest roentgenogram showed the presence of a giant mass and computed tomography
      (CT) of the chest confirmed the mass with an inhomogeneous density in the left
      hemithorax. A transthoracic TruCut needle biopsy of the mass showed benign
      fibrous tissue. The patient underwent a thoracotomy. A tumor arose from the
      visceral pleura of left lower lobe and pedinculated. Size of the tumor was 19 x
      18 x 7 cm and weighed 1500 g. It was successfully resected. The pathological
      diagnosis of the tumor was benign localized fibrous tumor of the pleura.

PMID- 9755011
TI  - Repair of aortico-right ventricular tunnel.
AB  - Aortico-right ventricular tunnel was successfully corrected in a 15-month-old
      child. Both the aortic and right ventricular openings were closed with pledgeted
      sutures. The coronary artery anatomy was normal. At 12-month follow-up the
      patient is in excellent clinical condition. Before surgical intervention for
      aortico-right ventricular tunnel is undertaken, every effort should be made to
      diagnose the coronary artery anatomy, because failure to do so in the case of
      aberrant origin of a coronary artery may prevent successful surgical correction.

PMID- 9755012
TI  - The effectiveness of diaphragmatic pedicled grafts in esophageal injuries and
      wall reconstruction.

PMID- 9755013
TI  - The clinical course and prognostic factors of non-specific neck pain: a
      systematic review.
AB  - Neck pain occurs frequently in western societies. In the majority of cases, no
      specific cause can be identified. In order to gain insight into the clinical
      course and prognostic factors of non-specific neck pain, a systematic review was
      conducted. A computerized literature search was carried out to identify
      observational studies on non-specific neck pain and randomized clinical trials
      (RCTs) on conservative treatment of non-specific neck pain. Two reviewers scored
      independently, the methodological quality of all identified publications, using a
      standardized set of 13 criteria which were divided into five categories according
      to: study population, study design, follow-up, outcome measures and analysis/data
      presentation. To determine prognosis per study, an overall percentage of recovery
      for the most important outcome measures (pain, general improvement, functional
      status, health care utilization and lost days of work) was calculated. In total
      23 eligible publications were identified (six observational studies and 17 RCTs).
      Only seven of 23 studies scored 50% or more of the 13 items, indicating a
      generally poor quality of methods. The most prevalent methodological shortcomings
      appeared to be selection of the study population, the sample size and analysis
      techniques. Most information regarding the clinical course is available for the
      group of patients with complaints for more than 6 months, who are treated in a
      secondary care or an occupational setting. In this group of patients, 46%
      (median) had less pain, with a range of 22-79% and a general improvement that
      ranged between 37 and 95% (47% median). The reduction in the use of analgesics
      ranged between 32 and 80% (37% median). Six studies reported on prognostic
      factors. Bearing in mind the limited number of studies and the low methodological
      quality, there are some indications that the localization (radiation to the
      arms/neurologic signs) and radiologic findings (degenerative changes in the discs
      and joints) are not associated with a worse prognosis. A higher severity of pain
      and a history of previous attacks however, seems to be associated with a worse
      prognosis.

PMID- 9755014
TI  - An experimental model for chronic compression of dorsal root ganglion produced by
      intervertebral foramen stenosis in the rat.
AB  - Under anesthesia and sterile surgery, a small stainless steel rod (4 mm in length
      and 0.5-0.8 mm in diameter) was inserted into the L5 intervertebral foramen in
      the rat, developing intervertebral foramen stenosis and hence producing a chronic
      steady compression of the dorsal root ganglion (DRG). The hind paw on the injured
      side exhibited a significant reduction in the latency of foot withdrawal to
      noxious heat and manifested a persistent heat hyperalgesia 5-35 days after
      surgery. Injection of 1% carrageenan into the intervertebral foramen, presumably
      causing inflammation of the DRG, also produced hyperalgesia to heat on the hind
      paw of the injured side 5-21 days after surgery. Extracellular
      electrophysiological recordings from myelinated dorsal root fibers were performed
      in vivo. Spontaneous activity was present in 21.5% of the fibers recorded from
      DRG neurons injured with chronic compression in contrast to 1.98% from uninjured
      DRG neurons. The pattern of spontaneous activity was periodic and bursting in
      75.3% of the spontaneously active fibers. These neurons had a greatly enhanced
      sensitivity to mechanical stimulation of the injured DRG and a prolonged after
      discharge. In response to TEA, topically applied to the DRG, excitatory responses
      were evoked in the injured, but not the uninjured, DRG neurons. Application of
      this experimental model may further our understanding of the neural mechanisms by
      which chronic compression of DRG induces low back pain and sciatica.

PMID- 9755015
TI  - The relationship between gender and family history of pain with current pain
      experience and awareness of pain in others.
AB  - This study aimed to evaluate the relationship between family history of pain and
      current pain experience in a student population. In a sample of 180 students who
      completed a pain history questionnaire there was a significant difference between
      males and females with women reporting significantly more pain models than men
      even when menstrual pain models were excluded from the analysis. There was also a
      difference on current pain symptoms, with women reporting more pain symptoms but
      this difference was no longer significant when menstrual pain was excluded. These
      results suggest that differences observed between sexes in a young student
      population in relation to current pain symptom reports may be accounted for by
      the presence of menstrual pain rather than by differences in family history of
      pain as it has previously been suggested. The higher incidence of pain models
      reported by females for menstrual as well as non-menstrual pain suggests a
      greater awareness of pain in others without implying a greater tendency for the
      young females as a group to report pain themselves.

PMID- 9755016
TI  - Pain coping strategies predict perceived control over pain.
AB  - Perceptions of control over pain and specific pain coping strategies are
      associated with a number of positive outcomes in patients with chronic pain
      conditions. Transactional models of stress have emphasized coping as a process
      that is both determined by, and influences appraisals of control. While
      perceptions of control and coping efforts are associated with better adjustment,
      little is known about the specific coping strategies that contribute to
      perceptions that pain is controllable. One hundred and ninety-five (65% female)
      individuals with chronic pain conditions admitted to an inpatient unit completed
      the Multidimensional Pain Inventory, the Survey of Pain Attitudes and the Coping
      Strategies Questionnaire. Stepwise multiple regression analyses were used to
      predict perceived pain control from measures of pain severity and coping. After
      controlling for pain severity and education, coping self-statements and
      reinterpreting pain sensations predicted greater perceptions of control over
      pain, whereas ignoring pain sensations predicted lower perceptions of control
      over pain. The coping strategies did not interact with pain severity in
      predicting perceptions of control. Coping flexibility, or the number of pain
      coping strategies reported at a high frequency, also predicted perceptions of
      control over pain and did not interact with pain severity. The present findings
      suggest that, regardless of pain severity, the use of specific cognitive pain
      coping strategies may increase perceptions of control over pain. Since the
      existing coping literature largely identifies maladaptive pain coping strategies,
      it is especially critical to establish which pain coping strategies are adaptive.
      Specific cognitive strategies, particularly coping self statements, are important
      components for cognitive-behavioral interventions for chronic pain management.
      Future research will need to determine whether other adaptive cognitive
      strategies such as reinterpreting pain sensations can be increased with cognitive
      interventions, since this strategy is infrequently used.

PMID- 9755017
TI  - The physical and psychological experience of pain: the effects of labeling and
      cold pressor temperature on three pain measures in college women.
AB  - Using the cold pressor test, three experiments were conducted to investigate the
      effects of water temperature and labeling on three dependent measures in college
      women: behavioral pain tolerance (BPT), a sensory rating of the pain experience
      (SR) and a parallel affective rating of the experience (AR). Temperature of the
      cold pressor was varied as the physical factor; labels (discomfort, pain,
      vasoconstriction pain) were varied as the psychological factor. Experiment I
      varied only water temperature; colder temperatures led to significantly lower BPT
      scores and significantly higher SR and AR scores. Experiment 2 varied only
      labeling and demonstrated that BPT decreased and AR increased as labels became
      more painful-sounding; in contrast, SR was unaffected by labeling. In Experiment
      3 both the psychological and physical factors were varied simultaneously. Results
      indicated significantly higher BPT scores as the water temperature increased and
      the pain label became more benign. In addition, both SR and AR were sensitive to
      changes in temperature, whereas only AR was affected by changes in labeling.

PMID- 9755018
TI  - Morphine, the NMDA receptor antagonist MK801 and the tachykinin NK1 receptor
      antagonist RP67580 attenuate the development of inflammation-induced progressive
      tactile hypersensitivity.
AB  - Normally-innocuous low-intensity tactile stimuli applied to inflamed tissue
      induce a progressive decrease in the mechanical flexion withdrawal threshold, the
      phenomenon of progressive tactile hypersensitivity (PTH). The effects of the mu
      opioid receptor agonist morphine, the non-competitive NMDA receptor antagonist
      MK801 and the tachykinin NK1 receptor antagonist RP67580 on the development and
      maintenance of PTH has now been investigated behaviourally in rats inflamed 48 h
      earlier by intraplantar complete Freund's adjuvant injection. A standard protocol
      of eight light tactile stimuli applied to the dorsum of the inflamed paw every 4
      s at 5 min intervals resulted, over 60 min, in a 70% fall in mechanical threshold
      from the pre-conditioning baseline value. Morphine administered before the
      tactile stimuli at 0.05 mg/kg i.p. had no effect on either baseline thresholds or
      PTH. At 0.5 mg/kg, morphine prevented the establishment of PTH without changing
      baseline thresholds. At 5 mg/kg morphine produced analgesia, increasing
      thresholds above the baseline. MK801 pre-treatment at 0.01 and 0.001 mg/kg i.p.
      significantly attenuated the development of progressive tactile hyperalgesia
      without an effect on basal thresholds. RP67580 pre-treatment at 0.1 mg/kg i.p.
      had no effect, but at both I and 10 mg/kg, attenuated progressive tactile
      hypersensitivity without changing baseline values. To test the effect of the
      drugs on established PTH, they were administered 90 min after the commencement of
      intermittent tactile stimulation to the inflamed hindpaw, when thresholds had
      reached a plateau. Morphine (0.5 mg/kg) and MK801 (0.01 mg/kg) produced only a
      small reduction in sensitivity and RP67580 (1 mg/kg) had no effect. These results
      suggest that the induction of inflammatory progressive tactile hypersensitivity
      is sensitive to morphine, and to a lesser extent NMDA and NKI receptor
      antagonists, but these compounds at a dose that do not alter baseline values, do
      not normalise established tactile hypersensitivity.

PMID- 9755019
TI  - Intrathecal administration of the mGluR compound, (S)-4CPG, attenuates
      hyperalgesia and allodynia associated with sciatic nerve constriction injury in
      rats.
AB  - The present study examined the effects of intrathecal (i.t.) treatment (twice
      daily injections on post-operative (PO) days 0-8) with the metabotropic glutamate
      receptor (mGluR) compound, (S)-4-carboxyphenylglycine ((S)-4CPG), or the non
      competitive N-methyl-D-aspartate (NMDA) antagonist, dizocilipine maleate (MK
      801), on mechanical allodynia and cold hyperalgesia associated with chronic
      constriction injury (CCI) of the sciatic nerve in rats. Also, the effects of
      early (twice-daily injections on days 0-3) or late (twice-daily injections on
      days 8-11) (S)-4CPG treatment on the injury-related mechanical allodynia and cold
      hyperalgesia were assessed in CCI rats. Results demonstrated that 8-day (S)-4CPG
      or MK-801 treatment attenuated mechanical allodynia (up to PO days 12 or 16,
      respectively) and cold hyperalgesia (up to PO days 8 or 16, respectively).
      Results also demonstrated that early (S)-4CPG treatment significantly attenuated
      the development of mechanical allodynia (90 and 270 nmol) and cold hyperalgesia
      (270 nmol). However, late treatment with (S)-4CPG did not reduce the nociceptive
      behaviours in either behavioural task. These data not only confirm that the NMDA
      receptor plays a role in chronic nociception, but also suggest that Group I
      mGluRs are more critically involved in the development, and not the maintenance,
      of mechanical allodynia and cold hyperalgesia associated with CCI in rats.

PMID- 9755020
TI  - Contributing factors to the persistence of musculoskeletal pain in
      preadolescents: a prospective 1-year follow-up study.
AB  - A 1-year follow-up of two preadolescent age cohorts with musculoskeletal pain at
      least once a week was conducted to analyze predictive factors for the persistence
      of musculoskeletal pain. Of the 564 children with pain at baseline, representing
      one third of the sample studied, 515 (91.3%) could be followed and 452 (80.1%)
      children with complete data were included for the logistic regression analysis. A
      structured questionnaire included questions on pain and also on several
      psychosomatic symptoms and amount of exercise. Joint hypermobility together with
      the questionnaire data were included in the logistic regression analysis. One
      half of subjects with pain at baseline still reported pain at follow-up,
      indicating persistent pain. Boys had a lower risk for the persistence of pain
      than girls and the risk for the persistence of pain increased 1.2 times per age
      year. When further adjusted for all the other studied risk determinants, high
      subjective disability index due to pain (OR 3.2, 95% CI 1.5-6.6) and day
      tiredness (OR 1.9, 95% CI 1.2-3.0) were the most significant predictors. This
      might indicate that psychological distress contributes to the persistence of non
      specific musculoskeletal pain of different locations in preadolescents. In
      clinical work not only pain but its interference with daily activities should be
      noticed.

PMID- 9755021
TI  - Treatment of myofascial trigger-points with ultrasound combined with massage and
      exercise--a randomised controlled trial.
AB  - The effect of treatment with ultrasound, massage and exercises on myofascial
      trigger-points (MTrP) in the neck and shoulder was assessed in a randomised
      controlled trial. The outcome measures were pain at rest and on daily function
      (Visual Analogue Scale, VAS), analgesic usage, global preference and index of
      MTrP. Long-term effect for treatment and control groups was assessed after 6
      months using a questionnaire. The patients were randomised to three groups. The
      first group was treated with ultrasound, massage and exercise (A), the second
      group with sham-ultrasound, massage and exercise (B), while the third group was a
      control group (C). The duration of the study was 6 weeks. Treatment was given
      twice a week from the second to the fifth week. The number and index of MTrPs
      were recorded at each treatment session in groups A and B but only at entry as
      well as end of study in group C. VAS and analgesic usage was recorded in all
      three groups throughout the study period. Six months after the last treatment
      session a questionnaire was send to the patients. A total of 67 patients were
      included. Nine patients dropped-out during the study, which left 58 patients that
      could be included in the final analysis. Twenty patients were randomised to group
      A, 18 to group B and 18 to group C. A significant reduction in index were found
      between treatment groups (A and B) and control group (C), but no difference
      between group A and B. VAS scores, analgesic usage or global preference showed no
      difference between group A, B or C. The patients in the group C were offered
      treatment (ultrasound, massage, exercise) after the 6 weeks treatment period. At
      the questionnaire after 6 month 44 (87%) of the 52 patients from all three groups
      who had treatment responded. Sixty-four percent answered that they had had good
      or some effects, 68 percent were still doing the exercise programme and 17
      percent had received other forms of therapy after they had completed the study.
      No difference between groups given ultrasound or sham ultrasound were found. It
      is concluded that US give no pain reduction, but apparently massage and exercise
      reduces the number and intensity of MTrP. The impact of this reduction on neck
      and shoulder pain is weak.

PMID- 9755022
TI  - Risk factors for back pain incidence in industry: a prospective study.
AB  - The objective of this study was to examine the relationship between physical and
      psychological risk factors on the one hand, and the occurrence of new episodes of
      back pain on the other hand. A prospective study was conducted with 12 months
      follow-up by means of self-administered questionnaires. The study took place in
      the Cargo Department of a major Dutch airline company. The subjects for this
      study were 270 workers involved in heavy physical work. Only workers without back
      pain at baseline were included. Self-reported back pain and sick leave due to
      back pain during the follow-up period were measured. Of the 238 workers included
      in the analysis, 73 (31%) developed a new episode of back pain during the follow
      up period, and 27 (11%) subjects reported sick leave due to back pain. Multiple
      logistic regression analysis showed that the history of back pain was the best
      predictor for the occurrence of a new episode of back pain during follow-up (OR
      9.8; 95% CI 2.8-34.4 for subjects who had back pain more than twice in the past
      year). Low job satisfaction was also associated with an increased risk for the
      occurrence of back pain during follow-up (OR 1.2; 95% CI 1.01-1.4). Riding a
      forklift truck appeared to be a protective factor for the occurrence of back pain
      (OR 0.7; 95% CI 0.5-0.99). In this study the best predictors for the occurrence
      of back pain were the history of back complaints and low job satisfaction.
      Although it needs to be confirmed by future intervention studies, the results
      indicate that increasing job satisfaction may be a successful (co-)intervention
      for the prevention of back pain at the workplace.

PMID- 9755023
TI  - Milacemide, a glycine pro-drug, inhibits strychnine-allodynia without affecting
      normal nociception in the rat.
AB  - The blockade of spinal glycine receptors with intrathecal (i.t.) strychnine (STR)
      produces reversible, segmentally localized allodynia in the rat. The purpose of
      this study was: (1) to investigate the effect of the anticonvulsant agent,
      milacemide, a glycine pro-drug on STR-allodynia; (2) to compare this effect with
      that of milacemide on normal nociception (without STR); and (3) to determine the
      sensitivity of the anti-allodynic effect of milacemide to pretreatment with
      selective monoamine oxidase (MAO)-A (clorgyline) and MAO-B (L-deprenyl)
      inhibitors. Male Sprague-Dawley rats, fitted with chronic i.t. catheters, were
      lightly anesthetized with urethane. Hair deflection (HD) evoked maximum changes
      in blood pressure and heart rate were recorded from left carotid artery, and
      cortical electroencephalographic (EEG) activity was continuously monitored using
      subdermal needle electrodes before and after i.t. STR (40 microg). Rats were
      pretreated with a single intravenous (i.v.) injection of milacemide (100-600
      mg/kg), 1 h before i.t. STR. To sustain the allodynic state, STR was injected
      every hour for up to 4 h. HD was applied to the affected dermatomes (2 min
      duration) using a cotton-tipped applicator at 5-min intervals for the duration of
      the STR effect. Normally innocuous HD elicited a marked increase in mean arterial
      blood pressure and heart rate, an immediate motor responses, and
      desynchronisation of EEG when applied to the cutaneous dermatomes affected by
      i.t. STR. Milacemide (100-600 mg/kg, i.v.) dose-dependently inhibited the heart
      rate and pressor responses (ED50 = 398 mg/kg; 95%CI = 196-873) and the motor
      responses (ED50 = 404 mg/kg; 95%CI = 275-727). Maximum inhibition was observed
      approximately 2 h after i.v. injection. The duration of action ranged from 3 h
      (400 mg/kg) to 4 h (600 mg/kg). Milacemide had no effect on the percent synchrony
      in the EEG. At the time of maximum inhibition of STR-allodynia (2 h post
      infusion), responses evoked by noxious pinch were unaffected by milacemide.
      Pretreatment with L-deprenyl (3 mg/kg, i.p.), but not clorgyline (10 mg/kg, i.p.)
      significantly blocked the anti-allodynic effect of milacemide (600 mg/kg i.v).
      These data indicate that i.v. milacemide significantly attenuates the allodynia
      arising from spinal glycine receptor blockade, and are consistent with: (1) the
      selective modulation of low threshold afferent input by STR-sensitive, glycine
      interneurons in the rat spinal cord; and (2) the pharmacological actions of
      milacemide as a glycine pro-drug.

PMID- 9755024
TI  - Treatment with either high or low frequency TENS reduces the secondary
      hyperalgesia observed after injection of kaolin and carrageenan into the knee
      joint.
AB  - For years, physical therapists have been utilizing a variety of modalities,
      including transcutaneous electrical nerve stimulation (TENS), in an attempt to
      manage pain associated with inflammation. However, the data on clinical
      effectiveness is conflicting and the neurophysiological mechanism of action is
      not known. The purpose of this study was to investigate the effects of high and
      low frequency TENS on the secondary hyperalgesia that occurs after joint
      inflammation. Secondary hyperalgesia is thought to reflect changes in central
      neurons and is thus a measure of activity of central neurons. This study utilized
      the kaolin and carrageenan model of knee joint inflammation and measured the
      effects of TENS treatment on paw withdrawal latency to radiant heat (secondary
      hyperalgesia), spontaneous pain behaviors and joint circumference. Either high
      (100 Hz) or low (4 Hz) frequency TENS was applied to the knee joint for 20 min
      after the development of hyperalgesia. Both high and low frequency TENS resulted
      in a reversal of the hyperalgesia immediately following treatment. The effects of
      high frequency TENS lasted through at least 24 h while those of low frequency
      TENS lasted through 12 h. There was no effect of TENS on spontaneous pain
      behaviors or joint swelling when compared to controls. Thus, TENS appears to be
      more effective in reducing referred pain (or secondary hyperalgesia) without
      affecting guarding or splinting of the affected limb. Thus, clinically, the
      choice to use TENS may depend on patient symptoms; specifically TENS should be
      effective in reducing referred or radiating pain.

PMID- 9755025
TI  - Comment on Manfredi et al.,Pain, 70 (1997) 199-101.

PMID- 9755026
TI  - The seasonal interrelationship between melatonin, vasopressin, and serum
      osmolality in elderly subjects.
AB  - Plasma concentration of arginine vasopressin (AVP) and melatonin and serum
      osmolality were measured at noon and at midnight in individuals living in the
      northern hemisphere on March 22-23, June 13-14, September 26-27, and December 12
      13 in 35 healthy volunteers (15 men and 20 women) aged 60-74 years. The nocturnal
      increase in melatonin was highest in the autumn and lowest in the winter in both
      sexes. The midnight serum osmolality level was lower in the autumn than in any
      other time of the year. In both the men and the women the AVP level was higher in
      winter than in any other season (P < 0.01 and P < 0.0001, respectively). In men,
      the AVP level was higher at noon than at midnight in 49% of the investigated 24
      hr periods, at the same level in 15% and lower in 36% (NS). The corresponding
      figures for women were 55%, 25%, and 20%, respectively (P < 0.05). This study
      suggests a possible relationship between melatonin and serum osmolality.

PMID- 9755027
TI  - Circadian secretion patterns of melatonin after major surgery.
AB  - Biorhythms, such as regular variation in core body temperature and the pattern of
      the secretion of melatonin, are thought to be mediated by the same biological
      clock. Core body temperature is affected by the inflammatory response to major
      surgery. Apart from the well-known inhibitory effect of bright light on its
      secretion, melatonin is an exceedingly good marker of one of the central
      generating systems of circadian rhythms. We sequentially measured the plasma
      melatonin concentration pattern in patients who had undergone esophagectomy with
      thoracotomy to elucidate the circadian rhythm after major surgery. From seven
      patients who had received esophagectomy with thoracotomy for esophageal cancer,
      plasma concentrations of melatonin were measured using an RIA method. Blood
      samples were collected via each patient's arterial line at 00.00, 02.00, 04.00,
      06.00, 08.00, 12.00, 16.00, 20.00, and 24.00 hr on the first postoperative day
      for six of the patients, and, for one patient, every 2 hr until the third
      postoperative day and every 4 hr thereafter until the sixth postoperative day.
      Four patients out of seven had melatonin concentrations of over 30 pg/ml (mean 34
      pg/ml) at 24.00 hr on the first postoperative day. Five patients showed circadian
      secretion patterns of melatonin during the first postoperative day. One patient
      whose melatonin concentrations were measured consecutively for 6 days showed a
      regular circadian secretion pattern through the 6 days of the study. Even the
      stress caused by extremely invasive surgery did not significantly disturb the
      melatonin secretion pattern.

PMID- 9755028
TI  - Protective effect of melatonin on cellular energy depletion mediated by
      peroxynitrite and poly (ADP-ribose) synthetase activation in a non-septic shock
      model induced by zymosan in the rat.
AB  - 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. Recently it was proposed
      that zymosan, a non-bacterial agent, causes cellular injury by inducing the
      production of peroxynitrite and consequent PARS activation. Here we investigated
      whether in vivo melatonin treatment inhibits cellular injury induced by
      peroxynitrite production and PARS activation in macrophages collected from rats
      subjected to zymosan-induced shock. Macrophages harvested from the peritoneal
      cavity exhibited a significant production of peroxynitrite, as measured by the
      oxidation of the fluorescent dye dihydrorhodamine 123. Furthermore, zymosan
      induced shock caused a suppression of macrophage mitochondrial respiration, DNA
      strand breakage, activation of PARS and reduction of cellular levels of NAD+. In
      vivo treatment with melatonin (25 and 50 mg/kg, intraperitoneally, 1 hr after
      zymosan injection) significantly reduced in dose-dependent manner peroxynitrite
      formation and prevented the appearance of DNA damage, the decrease in
      mitochondrial respiration, the loss of cellular levels of NAD+, and the PARS
      activation. Our study supports the view that the antioxidant and antiinflammatory
      effect of melatonin is also correlated with the inhibition of peroxynitrite
      production and PARS activation. In conclusion, melatonin may be a novel
      pharmacological approach to prevent cell injury in inflammation.

PMID- 9755029
TI  - Protective role of melatonin and retinol palmitate in oxidative stress and
      hyperlipidemic nephropathy induced by adriamycin in rats.
AB  - We have studied the effects of melatonin and retinol palmitate (RP) on the
      nephropathy and oxidative stress induced by a single and high dose of adriamycin
      (AD) in Wistar male rats. A dose of melatonin (75 microg/kg/day) and a dose of RP
      (0.25 g oily solution/kg/day, s.c.) were injected 3 and 9 days before and after
      the administration of AD (25 mg/kg, i.p.), respectively. After the decapitation,
      samples were taken from the neck vascular trunk in order to determine the
      triglycerides, total cholesterol, phospholipids, HDL-cholesterol, total proteins,
      urea, lipoperoxides, and reduced glutathione (GSH). We estimated the lipoperoxide
      and glutathione (GSH) contents in renal homogenates, and the excretion of
      proteins in urine over a 24 hr period. The administration of AD caused
      significant increases in proteinuria and in the other parameters studied [lipids
      (triglycerides, total cholesterol, phospholipids, and HDL-cholesterol), non
      protein nitrogen compounds, and lipoperoxides]. AD increased the lipoperoxide
      content, but it decreased the GSH content in the kidney. Both melatonin and RP,
      although melatonin more significantly, decreased the intensity of the changes
      produced by the administration of AD alone. In fact, melatonin was quite
      efficient in reducing the formation of lipoperoxides, restoring renal GSH content
      and decreasing remarkably the severity of proteinuria. These results support the
      powerful antioxidant action of melatonin at renal level and a lower antioxidant
      action of retinol. Likewise, these data reinforce the hypothesis which supports
      the pathogenetic role and the close relation between the oxidative stress and the
      expression of the nephropathy induced by AD. However, in spite of this obvious
      antioxidant effect of melatonin in the kidney, additional studies are required to
      establish accurately the role of this pineal indole in the regulation and
      dynamics of the antioxidative defense enzyme system, which neutralizes the
      damaging effect of free radicals, both endogenous and exogenous, in this organ.

PMID- 9755030
TI  - Oxidative stress in diabetic rats induced by streptozotocin: protective effects
      of melatonin.
AB  - We have studied the effect of the administration of two doses of melatonin
      (melatonin 100 and melatonin 200 microg/kg bw) on diabetes and oxidative stress
      experimentally induced by the injection of streptozotocin (STZ) in female Wistar
      rats. STZ was injected as a single dose (60 mg/kg i.p. in buffered citrate
      solution, pH 4.0) and melatonin (melatonin 100, 100 microg/kg/day i.p.; melatonin
      200, 200 microg/kg/day i.p.) beginning 3 days before diabetes induction and
      continuing until the end of the study (8 weeks). The parameters analysed to
      evaluate oxidative stress and the diabetic state were a) for oxidative stress,
      changes of lipoperoxides (i.e., malondialdehyde, MDA) in plasma and erythrocytes
      and the changes in reduced glutathione (GSH) in erythrocytes and b) for diabetes,
      changes in glycemia, lipids (triglycerides: TG; total cholesterol: TC; HDL
      cholesterol, HDL-c), percentage of glycosylated hemoglobin (Hb%), and plasma
      fructosamine. The injection of STZ caused significant increases in the levels of
      glycemia, percentage of glycosylated hemoglobin, fructosamine, cholesterol,
      triglycerides, and lipoperoxides in plasma and erythrocytes, whereas it decreased
      the levels of HDL-c and the GSH content in erythrocytes. The melatonin 100 dose
      reduced significantly all these increases, except the percentage of glycosylated
      hemoglobin. With regard to the decreases of plasma HDL-c and GSH content in
      erythrocytes, this melatonin dose returned them to normal levels. The melatonin
      200 dose produced similar changes, though the effects were especially noticeable
      in the decrease of glycemia (55% vs. diabetes), percentage of hemoglobin (P <
      0.001 vs diabetes), and fructosamine (31% vs. diabetes). This dose also reversed
      the decreases of HDL-c and GSH in erythrocytes. Both doses of melatonin caused
      significant reduction of the percentage of glycosylated hemoglobin in those
      groups that were non-diabetic. These illustrate the protective effect of
      melatonin against oxidative stress and the severity of diabetes induced by STZ.
      In particular, this study confirms two facts: 1) the powerful antioxidant action
      of this pineal indole and 2) the importance of the severity of oxidative stress
      to maintain hyperglycemia and protein glycosylation, two pathogenetic
      cornerstones indicative of diabetic complications. Melatonin reduces remarkably
      the degree of lipoperoxidation, hyperglycemia, and protein glycosylation, which
      gives hope to a promising perspective of this product, together with other
      biological antioxidants, in the treatment of diabetic complications where
      oxidative stress, either in a high or in a low degree, is present.

PMID- 9755031
TI  - Short photoperiod affects reproductive function but not dehydroepiandrosterone
      concentrations in male deer mice (Peromyscus maniculatus).
AB  - Cessation of breeding is central among the suite of winter-coping strategies used
      by small rodents to survive energy-demanding winter conditions. Animals use
      photoperiod to predict the onset of winter and initiate, well in advance of
      deteriorating conditions, seasonal adaptations. Exposure to short photoperiod
      leads to regression of the reproductive system in long-day breeding animals.
      Likewise, exposure to short days leads to enhanced immune function among several
      rodent species studied. Because dehydroepiandrosterone (DHEA) increases immune
      function in virtually all studies reported to date, we sought to determine if
      DHEA concentrations might be influenced by photoperiod, thereby suggesting a
      mechanism whereby short photoperiod may enhance immune function. Male deer mice
      (Peromyscus maniculatus) were exposed to either short or long days for 10 weeks.
      Short photoperiods caused significant reduction in all reproductive organs
      measured relative to animals housed in long days. However, DHEA concentrations
      did not differ between short- and long-day mice. Taken together, these data
      suggest that short-day enhancement of immune function in deer mice is independent
      of DHEA concentrations.

PMID- 9755032
TI  - Changes with age in daytime and nighttime contents of melatonin, indoleamines,
      and catecholamines in the pineal gland: a comparative study in rat and Syrian
      hamster.
AB  - Previous studies in rodents showed a severe deterioration of pineal physiology
      with aging. The present study investigated the age-related changes in the content
      of monoamines and metabolites in rat and Syrian hamster pineal gland. In addition
      to melatonin, the levels of 5-hydroxytryptophan (5HTP), serotonin (5HT), 5
      hydroxyindoleacetic acid (5HIAA), N-acetylserotonin (N-Ac-SHT), dopamine (DA),
      3,4-dihydroxyphenylacetic acid (DOPAC), and noradrenaline (NA) were measured by
      HPLC. Pronounced reductions were found in 5HT and 5HIAA contents during daytime
      in rats of 24 months, which had not been observed in animals of 12 months. In
      addition, nighttime pineal 5HIAA, N-Ac-5HT, and melatonin contents were decreased
      in the old rats, although a significant day:night variation persisted. Also a
      diurnal fluctuation in NA, DA, and DOPAC contents was present in young and middle
      aged rats but not for NA and DOPAC in the oldest rats due to a decrease in the
      nighttime levels. Pineal DA levels were also reduced in 24-month-old rats during
      the night, although a marked day:night change was still found. In the Syrian
      hamster pineal, significant reductions in daytime 5HT and 5HIAA were found
      respectively at 12 and 18 months, while nighttime levels of these compounds were
      decreased from 18 months. The nocturnal content of N-Ac-5HT dropped gradually
      from 12 months, and melatonin was reduced by 74% and 86% in hamsters of 18 and 24
      months, respectively. In all these compounds, a significant day:night variation
      was observed irrespective of age. However, neither a day:night variation nor an
      effect of aging was found in terms of pineal NA content. In contrast, pineal DA
      and DOPAC levels displayed a diurnal variation in hamsters of 1.5 and 6 months,
      but not in animals of 12 and 18 months due a reduced nighttime content. These
      data suggest that the decline of pineal melatonin with age is a consequence of a
      deficit in the pathway of serotonin utilization. This probably is explained by a
      reduced N-acetyltransferase activity, which may be linked to impaired pineal
      catecholaminergic neurotransmission.

PMID- 9755033
TI  - Changes in human plasma melatonin profiles in response to 50 Hz magnetic field
      exposure.
AB  - The effects of power-frequency magnetic fields on nighttime plasma melatonin were
      studied in a group of 30 adult male human subjects. Exposure consisted of 20
      microT (200 mG) at 50 Hz (circularly polarized) at certain times in relation to
      the predicted time of onset of rise in melatonin concentration for a particular
      individual (the time of onset was predicted from a previous screening night).
      Response to this exposure was compared to sham-exposure (in random order). When
      exposure preceded onset of rise, a significant delay in onset time relative to
      sham-exposure of approximately half an hour was observed, with indications
      (marginally significant) of a reduction in maximum melatonin level. Analysis of
      distribution of time-delays is consistent with two populations: those individuals
      who respond (around 20%) and those that do not. Magnetic fields generated by
      square-wave currents produce more marked reductions in the maximum level when
      compared to sinusoidal waveforms, but there was no significant difference in
      onset time.

PMID- 9755034
TI  - Axial stiffness of human lumbar motion segments, force dependence.
AB  - This paper addresses the axial stiffness of human lumbar motion segments while
      subjected to moderate loads. Impacts in axial direction were applied to
      Functional Spinal Units while they were subjected to weights acting as static pre
      load. Accelerations were recorded proximal and distal of the FSU. The transfer
      function and the resonant frequency were calculated from this data. The stiffness
      was calculated from the resonant frequency and the load. A simple non-linear
      model was fitted to the data and a linear relationship was found between
      stiffness squared and force. The non-linear component in the model strongly
      affected the stiffness within the chosen load range. The present model may allow
      in vivo dynamic force determination with improved accuracy, e.g. in experiments
      where accelerometers have been fixated to pins inserted into the spinous
      processes of lumbar vertebrae if the static force is known.

PMID- 9755035
TI  - One-year changes in hind limb kinematics, ground reaction forces and knee
      stability in an experimental model of osteoarthritis.
AB  - Long-term changes in the three-dimensional external loading, hind limb kinematics
      and knee stability were assessed in an anterior cruciate ligament (ACL)
      transected cat model of osteoarthritis (OA). Seven skeletally mature cats (mean
      mass 4.6+/-1.4 kg) were studied before ACL transection (ACLT) and at 1 and 3
      weeks, and at 3, 6, 9 and 12 months following ACLT. One week following ACLT,
      significant changes from the normal locomotion pattern were observed: peak
      vertical and anterior posterior ground reaction forces were decreased,
      particularly the peak posterior forces in the early phase of stance. Furthermore,
      knee angles were reduced by about 15 degrees throughout the whole gait cycle,
      while ankle and hip angles were reduced at paw off in the experimental compared
      to the contralateral hind limbs. Ground reaction forces and hind limb kinematics
      recovered to near pre-surgical patterns over the one year period assessed. ACLT
      was also associated with an increased knee instability which improved over time.
      X-rays suggested that there was a continued degeneration in the experimental knee
      over the one year period; there was osteophyte formation at the joint margins and
      an increase in cartilage thickness throughout the joint. It was speculated that
      the more flexed knee angles and the reduced anterior-posterior ground reaction
      forces in the ACL-transected compared to the intact hind limb represent an
      adaptive strategy aimed at avoiding excessive anterior displacement of the tibia
      in the early phase of stance. The recovery of the locomotion pattern with time
      might be related to the corresponding improvement of knee stability.

PMID- 9755036
TI  - Anterior cruciate ligament strain in-vivo: a review of previous work.
AB  - Disruption of the anterior cruciate ligament (ACL), a primary stabilizer of the
      knee, can produce disability. The purpose of our work has been to study the
      normal ACL in humans, in the presence of normal muscle function and body weight,
      and develop clinical criteria for reconstruction, establish a basis for
      rehabilitation programs, and evaluate how knee braces protect this important
      ligament. The strain behavior of the ACL has been measured by arthroscopic
      implantation of the Differential Variable Reluctance Transducer while subjects
      are under local anesthesia. Movement of the knee from a flexed to an extended
      position, either passively or through contraction of the leg muscles, produces an
      increase in ACL strain values. Isolated contraction of the dominant quadriceps
      with the knee between 50 degrees and extension creates substantial increases in
      strain. In contrast, isolated contraction of the hamstrings at any knee position
      does not increase strain. With the knee un-weighted, the protective strain
      shielding effect of a functional knee brace decreases as the magnitude of
      anterior shear load applied to the tibia increases. A different behavior occurs
      during weight bearing, the strain shielding effect of the brace remains constant
      as the magnitude of anterior load increases. Our approach is novel in that it can
      be used to measure on important portion of the ACLs strain distribution while
      clinically relevant loads are applied to the knee, subjects perform
      rehabilitation exercises, or in the presence of different orthoses such as
      functional knee braces.

PMID- 9755037
TI  - Asymmetric low back loading in asymmetric lifting movements is not prevented by
      pelvic twist.
AB  - Asymmetric lifting is associated with an increased risk of low back disorders.
      Especially in lifting movements, characterized by a small amount of asymmetry, it
      is still the question if asymmetric lumbosacral torques occur, or if subjects try
      to avoid asymmetric back loading by twisting their pelvis with respect to the
      feet. An increase of the lifting speed or the box weight might amplify the lumbar
      torques but might also result in an attempt to limit further increase of
      asymmetric torques by increasing pelvic twist. In the current study, asymmetrical
      lifting movements were analyzed with the aid of a 3D linked segment model, using
      cuffs mounted to the body segments. Eight subjects performed lifting movements
      with five different asymmetry conditions, ranging from 0 to 90 degrees lifting
      asymmetry with respect to the sagittal plane, using two lifting speeds and two
      box weights. A significant increase in lateral flexing and twisting low back
      torque was found for each increase in asymmetry of the lifting movement. Pelvic
      twist accounted more or less constantly for about 25% of the lifting asymmetry
      and was hardly influenced by lifting speed or box weight. Even for 10 or 30
      degrees of lifting asymmetry, subjects did not twist their pelvis far enough to
      avoid asymmetric loading of the low back. Assuming that asymmetric loading of the
      low back is more strenuous to the spine than symmetric loading, the current
      results indicate that even small deviations of a lifting movement from the
      sagittal plane can explain an increased risk of low back disorders.

PMID- 9755038
TI  - Degeneration affects the anisotropic and nonlinear behaviors of human anulus
      fibrosus in compression.
AB  - Axial and radial specimens of non-degenerate and degenerate human anulus fibrosus
      (AF) were tested in confined compression to test the hypothesis that degeneration
      significantly affects the compressive properties of AF. Due to the highly
      oriented structure of AF, a secondary objective was to investigate anisotropic
      behaviors of AF in compression. Uniaxial swelling and stress relaxation
      experiments were performed on site-matched samples of anulus from the anterior
      outer region of L2-3 intervertebral discs. The experimental stress-relaxation
      behavior was modeled using the finite deformation biphasic theory and a finite
      difference approximation scheme. Significant effects of degeneration but not
      orientation were detected for the reference stress offset, sigma(offset), and
      parameters describing the compressive stiffness (i.e. reference aggregate
      modulus, H(A0), and nonlinear stiffening coefficient, beta). Average values were
      0.13+/-0.06 and 0.05+/-0.05 MPa for sigma(offset), 0.56+/-0.21 and 1.10+/-0.53
      MPa for H(A0) and 2.13+/-1.48 and 0.44+/-0.61 for beta for all normal and
      degenerate specimens, respectively. No significant effect of degeneration or
      orientation were detected for either of the parameters describing the strain
      dependent permeability (i.e. reference permeability, k0 and strain-dependent
      permeability coefficient, M) with average values for all specimens of 0.20+/-0.10
      x 10(-15) m4/N-s and 1.18+/-1.30 for k0 and M, respectively. The loss of
      sigma(offset) was compensated with an elastic stiffening and change in the shape
      of the equilibrium stress-strain curve with H(A0) for degenerate tissues almost
      twice that of normal tissues and beta less than one sixth. The increase in
      reference elastic modulus with degeneration is likely related to an increase in
      tissue density resulting from the loss of water content. The significant effects
      of degeneration reported in this study suggested a shift in load carriage from
      fluid pressurization and swelling pressure to deformation of the solid matrix of
      the AF. The results also suggest that the highly organized and layered network of
      the anulus fibrosus, which gives rise to significant anisotropic effects in
      tension, does not play a major role in contributing to the magnitude of
      compressive stiffness or the mechanisms of fluid flow of the anulus in the
      confined compression configuration.

PMID- 9755039
TI  - Static torque-angle relation of human elbow joint estimated with artificial
      neural network technique.
AB  - Static relations between elbow joint angle and torque at constant muscle activity
      in normal volunteers were investigated with the aid of an artificial neural
      network technique. A subject sat on a chair and moved his upper- and forearm in a
      horizontal plane at the height of his shoulder. The subject was instructed to
      maintain the elbow joint at a pre-determined angle. The wrist was then pulled to
      extend the elbow joint by the gravitational force of a weight hanging from a
      pulley. Integrated electromyograms (IEMGs), elbow and shoulder joint angles and
      elbow joint torque were measured. Then the relation among IEMGs, joint angles and
      torque was modeled with the aid of the artificial neural network, where IEMGs and
      joint angles were the inputs and torque was the output. After back propagation
      learning, we presented various combinations of IEMGs, shoulder and elbow joint
      angles to the model and estimated the elbow joint torque to obtain the torque
      angle relation for constant muscle activation. The elbow joint torque increased
      and then decreased with extension of the elbow joint. This suggests that if the
      forearm is displaced from an equilibrium point, the torque angle relation would
      not act like a simple spring. In a view of the musculoskeletal structure of the
      elbow joint, the relation between the elbow joint angle and the moment arm of the
      elbow flexor muscles seems to have a dominant effect on the torque-angle
      relation.

PMID- 9755040
TI  - A Hill type model of rat medial gastrocnemius muscle that accounts for shortening
      history effects.
AB  - The aim of the present study was to develop a Hill type muscle model that
      accounts for the effects of shortening history. For this purpose, a function was
      derived that relates force depression to starting length, shortening amplitude
      and contraction velocity. History parameters were determined from short-range
      isokinetic experiments on rat medial gastrocnemius muscle (GM). Simulations of
      isokinetic as well as isotonic experiments were performed with the new model and
      a standard Hill type model. The simulation results were compared with
      experimental results of rat GM to evaluate if incorporation of history effects
      leads to improvements in model predictions. In agreement with the experimental
      results, the new model qualitatively described force reduction during and after
      isokinetic shortening as well as the experimental observation that isometric
      endpoints of isotonic contractions are attained at higher muscle lengths than is
      expected from the fully isometric length-force curve. Consequently, the new model
      gave a better quantitative prediction of the experimental results compared to the
      standard model. It was concluded that incorporation of history effects can
      improve the predictive power of a Hill type model considerably. The applicability
      of the model to conditions other than those described in the present paper is
      discussed.

PMID- 9755041
TI  - Mechanical advantage of the thumb muscles.
AB  - The purpose of this study was to measure the moment arms of four extrinsic
      muscles (flexor pollicis longus, extensor pollicis longus, extensor pollicis
      brevis, and abductor pollicis longus) and four intrinsic muscles (flexor pollicis
      brevis, abductor pollicis brevis, adductor pollicis, and opponents pollicis) of
      the thumb at the interphalangeal, the metacarpophalangeal, and the
      carpometacarpal joints in the same cadaver specimens and to examine the specific
      role of each muscle. Measurements were made on seven fresh frozen cadaver hands.
      The moment arms were measured during flexion/extension of the interphalangeal
      joint, flexion/extension and adduction/abduction of the metacarpophalangeal
      joint, and flexion/extension and adduction/abduction of the carpometacarpal
      joint. Moment arms were computed using the slope of the tendon excursion joint
      angle relationship. The specific function of each muscle was determined by
      multiplying the measured moment arms by the maximum force that each muscle can
      generate. It was found that the flexor pollicis longus was a pure flexor while
      flexor pollicis brevis was an adductor as well as a flexor, the extensor pollicis
      longus was an extensor and an adductor, extensor pollicis brevis was an extensor
      and a mild abductor, the abductor pollicis longus was an extensor as well as an
      abductor, the abductor pollicis brevis was mainly an abductor, the adductor
      pollicis was a major flexor as well as an adductor, and the opponents pollicis
      was a flexor and an abductor.

PMID- 9755042
TI  - A high-accuracy three-dimensional coordinate digitizing system for reconstructing
      the geometry of diarthrodial joints.
AB  - This paper describes the design and performance evaluation of a three-dimensional
      (3-D) coordinate digitizing system (3-DCDS) for measuring both soft and hard
      biological tissue. The system incorporates a visible semiconducting laser beam
      and an X-Y positioning table to directly measure 3-D coordinates that define
      surface points. Experiments conducted to evaluate the performance of the system
      showed that it delivers an accuracy of 0.1 microm in the Z-direction and 1.4
      microm in the X-Y plane, and an overall system root-mean-squared error (RMSE) of
      8 microm on surfaces with slopes of less than 45 degrees . This error is lower
      than that of previously reported measurement techniques. The 3-DCDS measures 3-D
      coordinates of surface points uniformly separated by 500 microm in the X-Y plane.
      Because the 3-DCDS is automated, the coordinates are measured efficiently and the
      accuracy is independent of operator skill. These highly accurate coordinates can
      be easily incorporated into nodal values for 3-D finite element models (FEM) of
      diarthrodial joints. To show the use of the 3-DCDS, the 3-D surface coordinates
      of human menisci were measured from a cadaver specimen.

PMID- 9755043
TI  - Focus on "exocytosis is not involved in activation of Cl- secretion via CFTR in
      Calu-3 airway epithelial cells".

PMID- 9755044
TI  - Exocytosis is not involved in activation of Cl- secretion via CFTR in Calu-3
      airway epithelial cells.
AB  - Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane
      conductance regulator (CFTR) Cl- channel, which mediates transepithelial Cl-
      transport in a variety of epithelia, including airway, intestine, pancreas, and
      sweat duct. In some but not all epithelial cells, cAMP stimulates Cl- secretion
      in part by increasing the number of CFTR Cl- channels in the apical plasma
      membrane. Because the mechanism whereby cAMP stimulates CFTR Cl- secretion is
      cell-type specific, our goal was to determine whether cAMP elevates CFTR-mediated
      Cl- secretion across serous airway epithelial cells by stimulating the insertion
      of CFTR Cl- channels from an intracellular pool into the apical plasma membrane.
      To this end we studied Calu-3 cells, a human airway cell line with a serous cell
      phenotype. Serous cells in human airways, such as Calu-3 cells, express high
      levels of CFTR, secrete antibiotic-rich fluid, and play a critical role in airway
      function. Moreover, dysregulation of CFTR-mediated Cl- secretion in serous cells
      is thought to contribute to the pathophysiology of cystic fibrosis lung disease.
      We report that cAMP activation of CFTR-mediated Cl- secretion across human serous
      cells involves stimulation of CFTR channels present in the apical plasma membrane
      and does not involve the recruitment of CFTR from an intracellular pool to the
      apical plasma membrane.

PMID- 9755045
TI  - Collagen gel overlay induces apoptosis of polarized cells in cultures:
      disoriented cell death.
AB  - In this study, we attempted to investigate the response of polarized cells to
      inappropriate interaction with the extracellular matrix. Cell lines of epithelial
      [Madin-Darby canine kidney (MDCK) and LLC-PK1], endothelial [bovine aortic
      endothelial cells (BAEC)], and mesenchymal (ESK-4 and NIH/3T3) origins were
      employed. With collagen gel overlay, MDCK cells underwent membrane remodeling and
      gradually developed lumen formation within 24 h. Apoptosis could also be observed
      following cell remodeling. The ratio of apoptosis was enhanced from 12.1 +/- 2.4%
      within 24 h to 58.4 +/- 9.8% at day 3, and finally the monolayer was
      disintegrated. Collagen gel overlay-induced apoptosis was not a result of
      physical stress, since agarose gel overlay did not induce any morphological
      alterations. All epithelial and endothelial cells examined developed apoptosis in
      response to collagen overlay. In contrast, collagen overlay did not affect growth
      of fibroblasts at all, although their growth under agarose gel was slightly
      hindered due to physical stress. Collagen overlay-induced apoptosis seems to be a
      unique phenomenon for polarized cells and thus is defined as "disoriented cell
      death." Furthermore, anti-alpha2-integrin antibody could abolish collagen overlay
      induced morphological changes and apoptosis in MDCK cells, indicating that
      signals through alpha2-integrin on the apical membrane are required for
      disoriented cell death. Finally, Bcl-2 overexpression prolonged survival of MDCK
      cells in response to collagen overlay, but these cells eventually developed
      apoptosis due to downregulation of Bcl-2 protein. These findings indicate that
      inappropriate cell-matrix interaction results in apoptosis, which may account for
      cell death mechanisms during developmental processes or under pathological
      conditions.

PMID- 9755046
TI  - Monocyte/macrophages evoke epithelial dysfunction: indirect role of tumor
      necrosis factor-alpha.
AB  - We examined the ability of monocytes (MPhi) activated by bacterial products to
      alter epithelial physiology. Confluent monolayers of the T84 colonic epithelial
      cell line were grown on filter supports and then cocultured in the presence of
      human MPhi with or without the activating agents bacterial lipopolysaccharide and
      the bacterial tripeptide formyl-methionyl-leucyl-phenylalanine. After 24 or 48 h,
      monolayers were mounted in Ussing chambers where parameters of epithelial
      function were measured. Exposure to activated MPhi resulted in a significant
      increase (P < 0.05) in baseline short-circuit current (250% after 48 h) that was
      associated with enhanced secretion of Cl-. In addition, epithelial permeability
      was significantly increased as shown by reduced transepithelial resistance and
      increased flux of 51Cr-EDTA. Activated MPhi produced substantial amounts
      (approximately 3 ng/ml at 48 h) of tumor necrosis factor-alpha (TNF-alpha). TNF
      alpha was identified as a key mediator acting via an autocrine mechanism to
      induce epithelial pathophysiology. Our data show that MPhi, when activated by
      common bacterial components, are potent effector cells capable of initiating
      significant changes in the transport and barrier properties of a model
      epithelium.

PMID- 9755048
TI  - In vivo and in vitro induction of c-fos in avian exocrine salt gland cells.
AB  - Osmotic stress in ducklings (Anas platyrhynchos) results in salt secretion and
      adaptive cell proliferation and differentiation in the nasal glands. We
      investigated whether osmotic stress in vivo or muscarinic ACh receptor activation
      in vitro changed the expression levels of the cellular protooncogene products Fos
      and Jun, which may play a role in the initiation of the adaptive processes. Using
      Fos- and Jun-specific polyclonal antisera in Western blot experiments, we
      demonstrated that Jun is constitutively expressed in nasal gland tissue, whereas
      Fos is not detectable in tissue from unstressed (naive) animals. Under conditions
      of osmotic stress imposed by replacing the drinking water of the animals with a
      1% NaCl solution, Jun protein remains constant in nasal gland tissue, whereas Fos
      protein is transiently upregulated. Treatment of cultured nasal gland tissue with
      muscarinic agonists results in a transcriptionally regulated expression of Fos in
      an atropine-sensitive manner. Immunohistochemical experiments show that Fos
      accumulation occurs in the nuclei of the secretory cells. These results indicate
      that the activation of the c-fos gene induced by muscarinic ACh receptor-mediated
      signaling pathways may play an important role in the initiation of adaptive
      growth and differentiation processes in nasal glands of osmotically stressed
      ducklings.

PMID- 9755047
TI  - Functional and molecular identification of a novel chloride conductance in canine
      colonic smooth muscle.
AB  - Swelling-activated or volume-sensitive Cl- currents are found in numerous cell
      types and play a variety of roles in their function; however, molecular
      characterization of the channels is generally lacking. Recently, the molecular
      entity responsible for swelling-activated Cl- current in cardiac myocytes has
      been identified as ClC-3. The goal of our study was to determine whether such a
      channel exists in smooth muscle cells of the canine colon using both molecular
      biological and electrophysiological techniques and, if present, to characterize
      its functional and molecular properties. We hypothesized that ClC-3 is present in
      colonic smooth muscle and is regulated in a manner similar to the molecular
      entity cloned from heart. Indeed, the ClC-3 gene was expressed in colonic
      myocytes, as demonstrated by reverse transcriptase polymerase chain reaction
      performed on isolated cells. The current activated by decreasing extracellular
      osmolarity from 300 to 250 mosM was outwardly rectifying and dependent on the Cl-
      gradient. Current magnitude increased and reversed at more negative potentials
      when Cl- was replaced by I- or Br-. Tamoxifen ([Z]-1-[p-dimethylaminoethoxy
      phenyl]-1,2-diphenyl-1-butene; 10 microM) and DIDS (100 microM) inhibited the
      current, whereas 25 microM niflumic acid, 10 microM nicardipine, and Ca2+ removal
      had no effect. Current was inhibited by 1 mM extracellular ATP in a voltage
      dependent manner. Cl- current was also regulated by protein kinase C, as phorbol
      12,13-dibutyrate (300 nM) decreased Cl- current magnitude, while chelerythrine
      chloride (30 microM) activated it under isotonic conditions. Our findings
      indicate that a current activated by hypotonic solution is present in colonic
      myocytes and is likely mediated by ClC-3. Furthermore, we suggest that the ClC-3
      may be an important mechanism controlling depolarization and contraction of
      colonic smooth muscle under conditions that impose physical stress on the cells.

PMID- 9755049
TI  - Cystic fibrosis transmembrane conductance regulator activation by cAMP
      independent mechanisms.
AB  - Recent studies have demonstrated that several compounds with diverse structures
      can activate wild-type cystic fibrosis transmembrane conductance regulator (CFTR)
      by non-receptor-mediated mechanisms. Some of these compounds have been shown to
      enhance cAMP-dependent activation of DeltaF508-CFTR. This study was undertaken to
      compare the mechanisms by which genistein, IBMX, milrinone, 8-cyclopentyl-1, 3
      dipropylxanthine (CPX), the benzimidazolone NS004, and calyculin A increase CFTR
      activity. Our studies demonstrate that, in transfected NIH-3T3 cells, maximal
      enhancements of forskolin-dependent DeltaF508-CFTR activity are greatest with
      genistein, IBMX, and NS004. Milrinone, genistein, CPX, NS004, and calyculin A do
      not increase cellular cAMP. Because forskolin and calyculin A increase in vivo
      phosphorylation of cAMP binding response element (CREB), the inability of
      milrinone, genistein, CPX, and NS004 to increase CREB phosphorylation suggests
      that they do not stimulate protein kinase A or inhibit phosphatase activity. Our
      data suggest that the mechanisms by which genistein and NS004 activate CFTR
      differ. We also demonstrate that, in NIH-3T3 cells, IBMX-dependent enhancement of
      cAMP-dependent CFTR activity is not due to an increase in cellular cAMP and may
      involve a mechanism like that of genistein.

PMID- 9755050
TI  - Electrophysiological characteristics of the proton-coupled peptide transporter
      PEPT2 cloned from rat brain.
AB  - We have cloned a peptide transporter from rat brain and found it to be identical
      to rat kidney PEPT2. In the present study we characterize the transport function
      of the rat brain PEPT2, with special emphasis on electrophysiological properties
      and interaction with N-acetyl-L-aspartyl-L-glutamate (NAAG). When heterologously
      expressed in HeLa cells and in SK-N-SH cells, PEPT2 transports several dipeptides
      but not free amino acids in the presence of a proton gradient. NAAG competes with
      other peptides for the PEPT2-mediated transport process. When PEPT2 is expressed
      in Xenopus laevis oocytes, substrate-induced inward currents are detectable with
      dipeptides of differing charge in the presence of a proton gradient. Proton
      activation kinetics are similar for differently charged peptides. NAAG is a
      transportable substrate for PEPT2, as evidenced by NAAG-induced currents. The
      Hill coefficient for protons for the activation of the transport of differently
      charged peptides, including NAAG, is 1. Although the peptide-to-proton
      stoichiometry for negatively charged peptides is 1, the transport nonetheless is
      associated with transfer of positive charge into the oocyte, as indicated by
      peptide-induced inward currents.

PMID- 9755051
TI  - Expression of myosin isoforms in smooth muscle cells in the corpus cavernosum
      penis.
AB  - Corpus cavernosum smooth muscle (CCSM) in the penis is unique in that it exhibits
      a high resting tone and, on stimulation, the muscle cells relax, allowing
      cavernous spaces to fill with blood, which results in an erection (tumescence).
      During detumescence, the muscle cells contract and return to the state of high
      resting tone. This study was undertaken to determine whether CCSM with these
      unique properties contains myosin isoforms typical of aorta or bladder smooth
      muscles, muscles that exhibit tonic and phasic characteristics, respectively. RT
      PCR revealed that normal CCSM contains an SM2/SM1 mRNA ratio of 1.2:1 (similar to
      the rabbit aorta). Approximately 31% of the myosin heavy chain transcripts
      possess a 21-nt insert (predominant in bladder smooth muscle but not expressed in
      aorta) that encodes the seven-amino acid insert near the NH2-terminal ATP binding
      region in the head portion of the myosin molecule found in SMB, with the
      remaining mRNA being noninserted (SMA). Quantitative competitive RT-PCR revealed
      that the CCSM possesses approximately 4.5-fold less SMB than the bladder smooth
      muscle. Western blot analysis using an antibody specific for the seven-amino acid
      insert reveals that both SM1 and SM2 in the CCSM contain the seven-amino acid
      insert. Furthermore, SMB containing the seven-amino acid insert was localized in
      the CCSM by immunofluorescence microscopy using this highly specific antibody.
      The analysis of the expression of LC17 isoforms a and b in the CCSM revealed that
      it is similar to that of bladder smooth muscle. Thus the CCSM possesses an
      overall myosin isoform composition intermediate between aorta and bladder smooth
      muscles, which generally express tonic- and phasiclike characteristics,
      respectively. Two-dimensional gel electrophoresis showed a relatively low level
      (approximately 10%) of Ca2+-dependent light-chain (LC20) phosphorylation at the
      basal tone, which reaches approximately 23% in response to maximal stimulation.
      The presence of noninserted and inserted myosin isoforms with low and high levels
      of actin-activated ATPase activities, respectively, in the CCSM may contribute to
      the ability of the CCSM to remain in a state of high resting tone and to relax
      rapidly for normal penile function.

PMID- 9755052
TI  - Cytokine-mediated PGE2 expression in human colonic fibroblasts.
AB  - We investigated prostanoid biogenesis in human colonic fibroblasts (CCD-18Co and
      5 primary fibroblast cultures) and epithelial cell lines (NCM460, T84, HT-29, and
      LS 174T) and the effect of PGE2 on fibroblast morphology. Cytokine-stimulated
      PGE2 production was measured. PGH synthase-1 and -2 (PGHS-1 and -2) protein and
      mRNA expression were evaluated. Basal PGE2 levels were low in all cell types
      (0.15-6.47 ng/mg protein). Treatment for 24 h with interleukin-1beta (IL-1beta;
      10 ng/ml) or tumor necrosis factor-alpha (50 ng/ml), respectively, elicited
      maximal 25- and 6-fold inductions of PGE2 synthesis in CCD-18Co cultures and
      similar results in primary fibroblast cultures; maximal inductions with IL-1beta
      in colonic epithelial cell lines were from zero to fivefold. Treatment of CCD
      18Co fibroblasts with IL-1beta caused maximal 21- and 53-fold increases,
      respectively, in PGHS-2 protein and mRNA levels without altering PGHS-1
      expression. PGE2 (0.1 micromol/l) elicited a dramatic shape change in selected
      fibroblasts. Colonic fibroblasts are potentially important as cytokine targets
      and a source of and target for colonic prostanoids in vivo.

PMID- 9755053
TI  - Characterization of two Mg2+ transporters in sealed plasma membrane vesicles from
      rat liver.
AB  - The plasma membrane of mammalian cells possesses rapid Mg2+ transport mechanisms.
      The identity of Mg2+ transporters is unknown, and so are their properties. In
      this study, Mg2+ transporters were characterized using a biochemically and
      morphologically standardized preparation of sealed rat liver plasma membranes
      (LPM) whose intravesicular content could be set and controlled. The system has
      the advantages that it is not regulated by intracellular signaling machinery and
      that the intravesicular ion milieu can be designed. The results indicate that 1)
      LPM retain trapped intravesicular total Mg2+ with negligible leak; 2) the
      addition of Na+ or Ca2+ induces a concentration- and temperature-dependent efflux
      corresponding to 30-50% of the intravesicular Mg2+; 3) the rate of flux is very
      rapid (137.6 and 86.8 nmol total Mg2+ . micrometer -2 . min-1 after Na+ and Ca2+
      addition, respectively); 4) coaddition of maximal concentrations of Na+ and Ca2+
      induces an additive Mg2+ efflux; 5) both Na+- and Ca2+-stimulated Mg2+ effluxes
      are inhibited by amiloride, imipramine, or quinidine but not by vanadate or Ca2+
      channel blockers; 6) extracellular Na+ or Ca2+ can stimulate Mg2+ efflux in the
      absence of Mg2+ gradients; and 7) Mg2+ uptake occurs in LPM loaded with Na+ but
      not with Ca2+, thus indicating that Na+/Mg2+ but not Ca2+/Mg2+ exchange is
      reversible. These data are consistent with the operation of two distinct Mg2+
      transport mechanisms and provide new information on rates of Mg2+ transport,
      specificity of the cotransported ions, and reversibility of the transport.

PMID- 9755054
TI  - Gating kinetics of Shaker K+ channels are differentially modified by general
      anesthetics.
AB  - The ShakerB K+ channel was used as a model voltage-gated channel to probe the
      interaction of volatile general anesthetics with gating mechanisms. The effects
      of three anesthetics, chloroform (CHCl3), isoflurane, and halothane, were studied
      using recombinant native and mutant Shaker channels expressed in Xenopus oocytes.
      Gating currents and macroscopic ionic currents were recorded with the cut-open
      oocyte voltage-clamp technique. The effects of CHCl3 and isoflurane on gating
      kinetics of noninactivating mutants were opposite, whereas halothane had no
      effect. The effects on ionic currents were also agent dependent: CHCl3 and
      halothane produced a reduction of the macroscopic conductance, whereas isoflurane
      increased it. The results indicate that the gating machinery of the channel is
      mostly insensitive to the anesthetics during activation until near the open
      state. The effects on the conductance are mainly due to changes in the
      transitions in and out of the open state. The data give support to direct protein
      anesthetic interactions. The magnitude and nature of the effects invite
      reconsideration of Shaker-like K+ channels as important sites of action of
      general anesthetics.

PMID- 9755055
TI  - Energy-dependent redox state of heme a + a3 and copper of cytochrome oxidase in
      perfused rat brain in situ.
AB  - Using the blood-free perfused rat brain, we examined the redox behavior of
      cytochrome oxidase of two chromophores, heme a + a3 and copper. When perfusate
      inflow was stopped to induce global ischemia, the reduction of heme a + a3 was
      triphasic, with a rapid phase, a slow phase, and a second rapid phase. In
      contrast, the reduction of copper was monophasic after the rapid phase of heme a
      + a3. The triphasic reduction of heme a + a3 was diminished by energy-depleting
      treatments, such as addition of an uncoupler. The time course of the reduction of
      copper was not affected by the energy depletion. During global ischemia the
      decrease in creatine phosphate nearly paralleled the reduction of heme a + a3,
      whereas ATP remained at the control level until approximately 60% of heme a + a3
      was reduced in the rapid phase. In the slow phase, ATP started to decrease with
      the reduction of copper. The redox behavior of copper was similar to the slow
      phase of the reduction of heme a + a3 because of the higher oxygen affinity of
      copper than of heme a + a3. Therefore, the rapid phase of the reduction of heme a
      + a3 can be used as an alarm before a decrease in ATP, whereas the reduction of
      copper indicates a decrease in ATP under severe hypoxia. Thus the copper signal
      in noninvasive near-infrared spectroscopy is a useful parameter for the clinical
      setting.

PMID- 9755056
TI  - Ascorbate and glutathione homeostasis in vascular smooth muscle cells:
      cooperation with endothelial cells.
AB  - Human umbilical vein smooth muscle cells (HUVSMCs) utilize extracellular cystine,
      glutathione (GSH), and N-acetylcysteine (NAC) to synthesize cellular GSH.
      Extracellular cystine was effective from 5 microM, whereas GSH and NAC were
      required at 100 microM for comparable effects. The efficacy of extracellular GSH
      was dependent on de novo GSH synthesis, indicating a dependence on cellular gamma
      glutamyltransferase (glutamyl transpeptidase). Coculture of syngenetic HUVSMCs
      and corresponding human umbilical vein endothelial cells (HUVECs) on porous
      supports restricted cystine- or GSH-stimulated synthesis of HUVSMC GSH when
      supplied on the "luminal" endothelial side. Thus HUVSMC GSH rapidly attained a
      steady-state level below that achieved in the absence of interposed HUVECs.
      HUVSMCs also readily utilize both reduced ascorbate (AA) and oxidized
      dehydroascorbate (DHAA) over the range 50-500 microM. Phloretin effectively
      blocked both AA- and DHAA-stimulated assimilation of intracellular AA, indicating
      a role for a glucose transporter in their transport. Uptake of extracellular AA
      was also sensitive to extracellular, but not intracellular, thiol depletion. When
      AA was applied to the endothelial side of the coculture model, assimilation of
      intracellular AA in HUVSMCs was restricted to a steady-state level below that
      achieved by free access.

PMID- 9755057
TI  - Cytosolic pH regulates GCl through control of phosphorylation states of CFTR.
AB  - Our objective in this study was to determine the effect of changes in luminal and
      cytoplasmic pH on cystic fibrosis transmembrane regulator (CFTR) Cl- conductance
      (GCl). We monitored CFTR GCl in the apical membranes of sweat ducts as reflected
      by Cl- diffusion potentials (VCl) and transepithelial conductance (GCl). We found
      that luminal pH (5.0-8.5) had little effect on the cAMP/ATP-activated CFTR GCl,
      showing that CFTR GCl is maintained over a broad range of extracellular pH in
      which it functions physiologically. However, we found that phosphorylation
      activation of CFTR GCl is sensitive to intracellular pH. That is, in the presence
      of cAMP and ATP [adenosine 5'-O-(3-thiotriphosphate)], CFTR could be
      phosphorylated at physiological pH (6.8) but not at low pH (approximately 5.5).
      On the other hand, basic pH prevented endogenous phosphatase(s) from
      dephosphorylating CFTR. After phosphorylation of CFTR with cAMP and ATP, CFTR GCl
      is normally deactivated within 1 min after cAMP is removed, even in the presence
      of 5 mM ATP. This deactivation was due to an increase in endogenous phosphatase
      activity relative to kinase activity, since it was reversed by the reapplication
      of ATP and cAMP. However, increasing cytoplasmic pH significantly delayed the
      deactivation of CFTR GCl in a dose-dependent manner, indicating inhibition of
      dephosphorylation. We conclude that CFTR GCl may be regulated via shifts in
      cytoplasmic pH that mediate reciprocal control of endogenous kinase and
      phosphatase activities. Luminal pH probably has little direct effect on these
      mechanisms. This regulation of CFTR may be important in shifting electrolyte
      transport in the duct from conductive to nonconductive modes.

PMID- 9755058
TI  - Cl- transport in an immortalized human epithelial cell line (NCM460) derived from
      the normal transverse colon.
AB  - Cells of a newly described, immortalized, epithelial, human transverse colonic
      cell line, NCM460, reach approximately 90% confluence on plastic and develop
      transepithelial resistances of 120-250 Omega . cm2 on porous substrates. Its
      utility as a model for the transverse human colon was validated by comparing
      second messenger-mediated Cl- transport, using the fluorescent probe 6-methoxy
      quinolyl acetoethyl ester, in NCM460 cells and colonocytes isolated from human
      transverse crypts. Basal Cl- influx was increased (P < 0.01) by PGE1 (1 microM),
      forskolin (1 microM), 8-bromoadenosine 3'5'-cyclic monophosphate (100 microM),
      heat-stable Escherichia coli enterotoxin (STa; 1 microM), 8-bromoguanosine 3'5'
      cyclic monophosphate (100 microM), histamine (1 microM), and phorbol 12,13
      dibutyrate (1 microM) in both cell types. The Cl- channel blocker diphenylamine 2
      carboxylic acid (50 microM) and the Na+-K+-2Cl- cotransport inhibitor furosemide
      (1 microM), but not the K+ channel blocker Ba2+ (3 mM), inhibited these Cl-
      permeabilities. These cells possess transcripts for cystic fibrosis transmembrane
      conductance regulator, Na+-K+-2Cl- cotransporter, STa receptor, and intestine
      specific cGMP-dependent protein kinase II. Thus cAMP-, cGMP-, and Ca2+-dependent
      secretagogues act on NCM460 and primary colonocytes to stimulate Cl- transport.
      This validates the utility of NCM460 as a model for transverse colonic crypts and
      is the first demonstration of a colonic cell line whose origin is known.

PMID- 9755059
TI  - NF-kappaB inactivation converts a hepatocyte cell line TNF-alpha response from
      proliferation to apoptosis.
AB  - Toxins convert the hepatocellular response to tumor necrosis factor-alpha (TNF
      alpha) stimulation from proliferation to cell death, suggesting that hepatotoxins
      somehow sensitize hepatocytes to TNF-alpha toxicity. Because nuclear factor
      kappaB (NF-kappaB) activation confers resistance to TNF-alpha cytotoxicity in
      nonhepatic cells, the possibility that toxin-induced sensitization to TNF-alpha
      killing results from inhibition of NF-kappaB-dependent gene expression was
      examined in the RALA rat hepatocyte cell line sensitized to TNF-alpha
      cytotoxicity by actinomycin D (ActD). ActD did not affect TNF-alpha-induced
      hepatocyte NF-kappaB activation but decreased NF-kappaB-dependent gene
      expression. Expression of an IkappaB superrepressor rendered RALA hepatocytes
      sensitive to TNF-alpha-induced apoptosis in the absence of ActD. Apoptosis was
      blocked by caspase inhibitors, and TNF-alpha treatment led to activation of
      caspase-2, caspase-3, and caspase-8 only when NF-kappaB activation was blocked.
      Although apoptosis was blocked by the NF-kappaB-dependent factor nitric oxide
      (NO), inhibition of endogenous NO production did not sensitize cells to TNF-alpha
      induced cytotoxicity. Thus NF-kappaB activation is the critical intracellular
      signal that determines whether TNF-alpha stimulates hepatocyte proliferation or
      apoptosis. Although exogenous NO blocks RALA hepatocyte TNF-alpha cytotoxicity,
      endogenous production of NO is not the mechanism by which NF-kappaB activation
      inhibits this death pathway.

PMID- 9755060
TI  - Modeling cell volume regulation in nonexcitable cells: the roles of the Na+ pump
      and of cotransport systems.
AB  - The purpose of this study is to contribute to understanding the role of Na+-K+
      ATPase and of ionic cotransporters in the regulation of cell volume, by employing
      a model that describes the rates of change of the intracellular concentrations of
      Na+, K+, and Cl-, of the cell volume, and of the membrane potential. In most
      previous models of dynamic cellular phenomena, Na+-K+-ATPase is incorporated via
      phenomenological formulations; the enzyme is incorporated here via an explicit
      kinetic scheme. Another feature of the present model is the capability to perform
      short-term cell volume regulation mediated by cotransporters of KCl and NaCl. The
      model is employed to perform numerical simulations for a "typical" nonpolarized
      animal cell. Basically, the results are consistent with the view that the Na+
      pump mainly plays a long-term role in the maintenance of the electrochemical
      gradients of Na+ and K+ and that short-term cell volume regulation is achieved
      via passive transport, exemplified in this case by the cotransport of KCl and
      NaCl.

PMID- 9755062
TI  - Heme oxygenase-1 induction in skeletal muscle cells: hemin and sodium
      nitroprusside are regulators in vitro.
AB  - The heat shock protein heme oxygenase-1 (HO-1) is regulated by a variety of
      physiological and pharmacological factors. In skeletal muscle tissue, HO-1 has
      been shown to be induced only by exercise and electrical stimulation in vivo.
      Both hemin and sodium nitroprusside (SNP) are potent inducers of HO-1 in other
      tissues. In this study, we examined the effects of these two agents on HO-1
      induction in L6.G8 rat skeletal myoblast cells. Hemin and SNP increased cellular
      heme oxygenase activity in both a time- and concentration-dependent manner.
      Increases in the HO-1 mRNA level and protein expression accompanied changes in
      heme oxygenase activity. The ability of SNP to induce HO-1 in L6.G8 cells was
      reduced by coincubation with hydroxocobalamin, a known nitric oxide (NO)
      scavenger, suggesting that NO itself may be involved in HO-1 gene stimulation.
      These results indicate that HO-1 expression is sensitive to both hemin and SNP in
      skeletal myoblast cells and may indicate an important regulatory mechanism of
      heme catabolism in skeletal muscle tissue.

PMID- 9755061
TI  - A role for MAP kinase in differentiated smooth muscle contraction evoked by alpha
      adrenoceptor stimulation.
AB  - The purpose of this study was to investigate the potential role of mitogen
      activated protein (MAP) kinase in smooth muscle contraction by monitoring MAP
      kinase activation, caldesmon phosphorylation, and contractile force during
      agonist stimulation. Isometric tension in response to KCl and phenylephrine (PE)
      was measured from strips of ferret aorta. MAP kinase activation was monitored by
      Western blot using a phosphospecific p44/p42 MAP kinase antibody. Caldesmon
      phosphorylation was assessed using specific phosphocaldesmon antibodies. We
      report here that treatment of smooth muscle strips with PD-098059, a specific
      inhibitor of MAP kinase kinase, did not detectably modify the KCl-evoked
      contraction but significantly inhibited the contraction to PE in the absence of
      extracellular Ca2+. In this experimental condition, where the contraction occurs
      in the absence of increases in 20-kDa myosin light chain phosphorylation, PD
      098059 also inhibited significantly MAP kinase and caldesmon phosphorylation.
      Collectively, these results demonstrate a direct cause-and-effect relationship
      between MAP kinase activation and Ca2+-independent smooth muscle contraction and
      support the concept of caldesmon phosphorylation as the missing link between both
      events.

PMID- 9755063
TI  - Minor role of a Ca2+-depleted sarcoplasmic reticulum in heterologous
      desensitization of smooth muscle to K+.
AB  - Exposure of porcine carotid artery smooth muscle (PCASM) to histamine was
      followed by a large reduction in the rate of force generation in response to 40
      mM KCl. This was shown to be a manifestation of slow attainment of a steady-state
      myoplasmic Ca2+ concentration ([Ca2+]i). We hypothesized that if net
      transsarcolemmal Ca2+ flux into the depolarized PCASM cells is the same before
      and after a desensitizing histamine treatment, then the transient attenuation of
      the increase in [Ca2+]i may be due to accelerated uptake of Ca2+ by a partially
      depleted sarcoplasmic reticulum (SR) acting as a Ca2+ sink or superficial buffer
      barrier. We tested this hypothesis by eliciting responses of "desensitized PCASM"
      to 40 mM KCl in the presence of cyclopiazonic acid (CPA), an SR Ca2+-ATPase
      inhibitor. Contractions of CPA-treated tissues were attenuated less than those of
      tissues not treated with CPA, but they were not abolished. CPA-insensitive
      mechanism(s) dominated the desensitization. We conclude that histamine
      pretreatment reduced net transsarcolemmal Ca2+ flux into PCASM in response to 40
      mM KCl.

PMID- 9755064
TI  - Hypotonicity activates transcription through ERK-dependent and -independent
      pathways in renal cells.
AB  - Acute hypotonic shock (50% dilution of medium with sterile water, but not with
      isotonic NaCl) activated the extracellular signal response kinase (ERK) mitogen
      activated protein (MAP) kinases in renal medullary cells, as measured by Western
      analysis with a phospho-ERK-specific antibody and by in vitro kinase assay of
      epitope-tagged ERKs immunoprecipitated from stable HA-ERK transfectants.
      Hypotonicity also activated the transcription factor and ERK substrate Elk-1 in a
      partially PD-98059-sensitive fashion, as assessed by chimeric reporter gene
      assay. Consistent with these data, hypotonic stress activated transcription of
      the immediate-early gene transcription factor Egr-1 in a partially PD-98059
      sensitive fashion. Hypotonicity-inducible Egr-1 transcription was mediated in
      part through 5'-flanking regions containing serum response elements and in part
      through the minimal Egr-1 promoter. Elimination of the Ets motifs adjacent to key
      regulatory serum response elements in the Egr-1 promoter diminished the effect of
      hypotonicity but failed to abolish it. Interestingly, hypotonicity also
      transiently activated p38 and c-Jun NH2-terminal kinase 1, as determined by
      immunoblotting with anti-phospho-MAP kinase antibodies. Taken together, these
      data strongly suggest that hypotonicity activates immediate-early gene
      transcription in renal medullary cells via MAP kinase kinase-dependent and 
      independent mechanisms.

PMID- 9755065
TI  - Identification of the pH sensor and activation by chemical modification of the
      ClC-2G Cl- channel.
AB  - Rabbit and human ClC-2G Cl- channels are voltage sensitive and activated by
      protein kinase A and low extracellular pH. The objective of the present study was
      to investigate the mechanism involved in acid activation of the ClC-2G Cl-
      channel and to determine which amino acid residues play a role in this acid
      activation. Channel open probability (Po) at +/-80 mV holding potentials
      increased fourfold in a concentration-dependent manner with extracellular H+
      concentration (that is, extracellular pH, pHtrans), with an apparent acidic
      dissociation constant of pH 4.95 +/- 0.27. 1-Ethyl-3(3
      dimethylaminopropyl)carbodiimide-catalyzed amidation of the channel with glycine
      methyl ester increased Po threefold at pHtrans 7.4, at which the channel normally
      exhibits low Po. With extracellular pH reduction (protonation) or amidation,
      increased Po was due to a significant increase in open time constants and a
      significant decrease in closed time constants of the channel gating, and this
      effect was insensitive to applied voltage. With the use of site-directed
      mutagenesis, the extracellular region EELE (amino acids 416-419) was identified
      as the pH sensor and amino acid Glu-419 was found to play the key or predominant
      role in activation of the ClC-2G Cl- channel by extracellular acid.

PMID- 9755066
TI  - Early changes in muscle fiber size and gene expression in response to spinal cord
      transection and exercise.
AB  - Muscles of spinal cord-transected rats exhibit severe atrophy and a shift toward
      a faster phenotype. Exercise can partially prevent these changes. The goal of
      this study was to investigate early events involved in regulating the muscle
      response to spinal transection and passive hindlimb exercise. Adult female
      Sprague-Dawley rats were anesthetized, and a complete spinal cord transection
      lesion (T10) was created in all rats except controls. Rats were killed 5 or 10
      days after transection or they were exercised daily on motor-driven bicycles
      starting at 5 days after transection and were killed 0.5, 1, or 5 days after the
      first bout of exercise. Structural and biochemical features of soleus and
      extensor digitorum longus (EDL) muscles were studied. Atrophy was decreased in
      all fiber types of soleus and in type 2a and type 2x fibers of EDL after 5 days
      of exercise. However, exercise did not appear to affect fiber type that was
      altered within 5 days of spinal cord transection: fibers expressing myosin heavy
      chain 2x increased in soleus and EDL, and extensive coexpression of myosin heavy
      chain in soleus was apparent. Activation of satellite cells was observed in both
      muscles of transected rats regardless of exercise status, evidenced by increased
      accumulation of MyoD and myogenin. Increased expression was transient, except for
      MyoD, which remained elevated in soleus. MyoD and myogenin were detected both in
      myofiber and in satellite cell nuclei in both muscles, but in soleus, MyoD was
      preferentially expressed in satellite cell nuclei, and in EDL, MyoD was more
      readily detectable in myofiber nuclei, suggesting that MyoD and myogenin have
      different functions in different muscles. Exercise did not affect the level or
      localization of MyoD and myogenin expression. Similarly, Id-1 expression was
      transiently increased in soleus and EDL upon spinal cord transection, and no
      effect of exercise was observed. These results indicate that passive exercise can
      ameliorate muscle atrophy after spinal cord transection and that satellite cell
      activation may play a role in muscle plasticity in response to spinal cord
      transection and exercise. Finally, the mechanisms underlying maintenance of
      muscle mass are likely distinct from those controlling myosin heavy chain
      expression.

PMID- 9755068
TI  - Increased NHE2 expression in rat intestinal epithelium during ontogeny is
      transcriptionally mediated.
AB  - We have previously described changes in intestinal brush-border membrane vesicle
      (BBMV) Na+/H+ exchange activity and characterized Na+/H+ exchanger (NHE3)
      expression during rat ontogeny. The current studies were designed to investigate
      developmental changes in NHE2 expression in rat intestine. In previous studies,
      pH-dependent uptake of Na+ in jejunal BBMV utilizing HOE-694 inhibition
      demonstrated that NHE2 functional protein levels were lowest in 2-wk-old rats,
      higher in 3-wk-old and adult rats, and highest in 6-wk-old rats [Collins et al.
      Am. J. Physiol. 273 (Cell Physiol. 42): C1937-C1946, 1997]. In the current
      investigation, Northern blot analyses showed that NHE2 mRNA levels in the jejunum
      were similar in 6-wk-old, adult, and 3-wk-old rats and three- to fivefold lower
      in 2-wk-old rats. In situ hybridization of 2- and 6-wk-old rat intestine with
      NHE2-specific probes confirmed Northern blot observations. Polyclonal antibodies
      were developed against an NHE2-specific peptide from amino acids 652-661. Western
      blots with NHE2 antiserum showed that the intensity of a specific 90-kDa band was
      lowest in 2-wk-old animals and four- to sixfold higher in 3- and 6-wk-old and
      adult animals. Immunohistochemical analysis showed specific staining of NHE2
      antiserum to only the apical intestinal membrane. Furthermore, nuclear run-on
      analyses showed a 1.7-fold higher NHE2 transcription rate in 6-wk-old rats than
      in 2-wk-old rats. Overall, the current data suggest that increases in NHE2
      expression upon weaning are mediated by increased gene transcription.

PMID- 9755067
TI  - Proton secretion in the male reproductive tract: involvement of Cl--independent
      HCO-3 transport.
AB  - The lumen of the epididymis is the site where spermatozoa undergo their final
      maturation and acquire the capacity to become motile. An acidic luminal fluid is
      required for the maintenance of sperm quiescence and for the prevention of
      premature activation of acrosomal enzymes during their storage in the cauda
      epididymis and vas deferens. We have previously demonstrated that a vacuolar H+
      ATPase [proton pump (PP)] is present in the apical pole of apical and narrow
      cells in the caput epididymis and of clear cells in the corpus and cauda
      epididymis and that this PP is responsible for the majority of proton secretion
      in the proximal vas deferens. We now show that PP-rich cells in the vas deferens
      express a high level of carbonic anhydrase type II (CAII) and that acetazolamide
      markedly inhibits the rate of proton secretion by 46.2 +/- 6.1%. The rate of
      acidification was independent of Cl- and was strongly inhibited by SITS under
      both normal and Cl--free conditions (50.6 +/- 5.0 and 57. 5 +/- 6.0%,
      respectively). In the presence of Cl-, diphenylamine-2-carboxylate (DPC) had no
      effect, whereas SITS inhibited proton secretion by 63.7 +/- 11.3% when applied
      together with DPC. In Cl--free solution, DPC markedly inhibited proton efflux by
      45.1 +/- 7.6%, SITS produced an additional inhibition of 18.2 +/- 6.6%, and
      bafilomycin had no additive effect. In conclusion, we propose that CAII plays a
      major role in proton secretion by the proximal vas deferens. Acidification does
      not require the presence of Cl-, but DPC-sensitive Cl- channels might contribute
      to basolateral extrusion of HCO-3 under Cl--free conditions. The inhibition by
      SITS observed under both normal and Cl--free conditions indicates that a Cl-/HCO
      3 exchanger is not involved and that an alternative HCO-3 transporter
      participates in proton secretion in the proximal vas deferens.

PMID- 9755070
TI  - Loading pyranine via purinergic receptors or hypotonic stress for measurement of
      cytosolic pH by imaging.
AB  - Although used extensively for the measurement of intracellular pH, derivatives of
      fluorescein such as 2', 7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF)
      have suboptimal sensitivity and can generate toxic photoproducts. These
      limitations can be overcome using the pH-sensitive fluorescent dye 8
      hydroxypyrene-1,3,6-trisulfonic acid (pyranine), which has improved spectroscopic
      properties. However, the use of pyranine has been limited by the difficulties
      encountered in delivering this highly hydrophilic dye to the cell interior. We
      describe a strategy for intracellular delivery of pyranine based on the
      reversible activation of purinergic P2x7 receptors, which allow permeation of the
      dye into otherwise intact cells. When loaded into J774 or RAW cells by this
      method, pyranine is not only more sensitive than BCECF (the dynamic range is
      approximately 7-fold greater), but is retained better and is less toxic. Pyranine
      was distributed throughout the cytosol but was not detectable in endomembrane
      compartments. Repeated illumination resulted in blebbing and loss of functional
      responsiveness of cells loaded with BCECF, whereas comparably irradiated cells
      loaded with pyranine remained healthy and responsive. Pyranine can also be loaded
      into cells not expressing P2x7 receptors by brief exposure to a hypotonic
      solution. The properties of cells labeled by this method are similar to those
      loaded via purinergic receptors and compare favorably with those of BCECF-loaded
      cells. Pyranine thus provides a useful alternative to fluorescein derivatives for
      the measurement of intracellular pH, particularly when using the high excitation
      intensities required for microscopic digital imaging.

PMID- 9755069
TI  - Localization and expression of AQP5 in cornea, serous salivary glands, and
      pulmonary epithelial cells.
AB  - Aquaporin (AQP) 5 gene was recently isolated from salivary gland and identified
      as a member of the AQP family. The mRNA expression and localization have been
      examined in several organs. The present study was focused on elucidation of AQP5
      expression and localization in the eye, salivary gland, and lung in rat. RNase
      protection assay confirmed intense expression of AQP5 mRNA in these organs but
      negligible expression in other organs. To examine the mRNA expression sites in
      the eye, several portions were microdissected for total RNA isolation. AQP5 mRNA
      was enriched in cornea but not in other portions (retina, lens, iris/ciliary
      body, conjunctiva, or sclera). AQP5 was selectively localized on the surface of
      corneal epithelium in the eye by immunohistochemistry and immunoelectron
      microscopy using an affinity-purified anti-AQP5 antibody. AQP5 was also localized
      on apical membranes of acinar cells in the lacrimal gland and on the microvilli
      protruding into intracellular secretory canaliculi of the serous salivary gland.
      In the lung, apical membranes of type I pulmonary epithelial cells were also
      immunostained with the antibody. These findings suggest a role of AQP5 in water
      transport to prevent dehydration or to secrete watery products in these tissues.

PMID- 9755071
TI  - Purification of active Na+-K+-ATPase using a new ouabain-affinity column.
AB  - Ouabain, a specific inhibitor of Na+-K+-ATPase, was coupled to epoxy agarose via
      a 13-atom spacer to make an affinity column that specifically binds Na+-K+
      ATPase. Na+-K+-ATPase from rat and dog kidney was bound to the column and was
      eluted as a function of enzyme conformation, altered by adding specific
      combinations of ligands. Na+-K+-ATPase from both sources bound to the column in
      the presence of Na + ATP + Mg and in solutions containing 30 mM K. No binding was
      observed in the presence of Na or Na + ATP. These experiments suggest that Na+-K+
      ATPase binds to the column under the same conditions that it binds to untethered
      ouabain. Na+-K+-ATPase already bound to the column was competitively eluted with
      excess free Na + ouabain or with Na + ATP. The latter eluted active enzyme. For
      comparable amounts of bound Na+-K+-ATPase, Na + ouabain and Na + ATP eluted more
      rat than dog Na+-K+-ATPase, consistent with the lower affinity of the rat Na+-K+
      ATPase for ouabain. The ouabain-affinity column was used to purify active Na+-K+
      ATPase from rat kidney microsomes and rat adrenal glomerulosa cells. The specific
      activity of the kidney enzyme was increased from approximately 2 to 15 micromol
      Pi . mg-1 . min-1. Na+-K+-ATPase purified from glomerulosa cells that were
      prelabeled with [32P]orthophosphate was phosphorylated on the alpha-subunit,
      suggesting that these cells contain a kinase that phosphorylates Na+-K+-ATPase.

PMID- 9755072
TI  - Transduction pathways involved in rapid hormone receptor regulation in the
      mammary epithelium.
AB  - Previous studies have shown that the envelope protein of the mouse mammary tumor
      virus (MMTV) rapidly upregulates prolactin (PRL) receptors by shifting them from
      internal pools to the cell surface and downregulates epidermal growth factor
      (EGF) receptors by inducing their internalization and degradation. This study
      shows that the effect on PRL receptors is mediated by the nitric oxide (NO)/cGMP
      pathway, since it can be mimicked by an NO donor or 8-bromo-cGMP and can be
      blocked by an NO synthase inhibitor. In contrast, the effect on EGF receptors is
      mediated by tyrosine phosphorylation and phosphatidylinositol 3-kinase (PI3K),
      since it can be blocked by either a tyrosine kinase inhibitor or by a PI3K
      inhibitor. Both of these pathways can be activated by a calcium ionophore and
      inhibited by calcium chelation. Therefore, it appears that the mouse mammary
      tumor virus envelope protein, like other retroviral envelope proteins, initially
      elevates cytoplasmic calcium, which can then stimulate both the NO/cGMP and the
      tyrosine phosphorylation/PI3K pathways, leading to PRL receptor upregulation and
      EGF receptor downregulation, respectively.

PMID- 9755073
TI  - Insulin does not change the intracellular distribution of hexokinase in rat
      heart.
AB  - Preliminary evidence has suggested that hexokinase in rat heart changes its
      kinetic properties in response to insulin through translocation to the outer
      mitochondrial membrane. We reexamined this hypothesis in light of tracer kinetic
      evidence to the contrary. Our methods were as follows. Working rat hearts were
      perfused with Krebs-Henseleit buffer containing glucose (5 mmol/l) and sodium
      oleate (0.4 mmol/l). Dynamic glucose uptake was measured with [2-3H]glucose and
      with 2-deoxy-2-[18F]fluoroglucose (2-[18F]DG). Hexokinase activity was determined
      in the cytosolic and mitochondrial fractions. Our results are as follows. Uptake
      of glucose and uptake of 2-[18F]DG were parallel. Insulin (1 mU/ml) increased
      glucose uptake threefold but had no effect on 2-[18F]DG uptake. The tracer-to
      tracee ratio decreased significantly. The Michaelis-Menten constant of hexokinase
      for 2-deoxyglucose was up to 10 times higher than for glucose. There was no
      difference in maximal reaction velocity. Two-thirds of hexokinase was bound to
      mitochondria. Insulin neither caused translocation nor changed Michaelis-Menten
      constant or maximal reaction velocity. In conclusion, the insulin-induced changes
      in the tracer-to-tracee ratio are due to a shift of the rate-limiting step for
      glucose uptake from transport to phosphorylation by hexokinase. Insulin does not
      affect the intracellular distribution or the kinetics of hexokinase.

PMID- 9755074
TI  - Altered ATP sensitivity of ATP-dependent K+ channels in diabetic rat hearts.
AB  - The effects of streptozotocin-induced diabetes (5-7 days or 7 wk) on cardiac ATP
      sensitive potassium channels (KATP channels) were investigated with the use of
      single-channel and action potential recordings from dissociated ventricular
      myocytes isolated from control and diabetic rat hearts. In inside-out patches
      from diabetic myocytes (5-7 days), the IC50 for ATP inhibition was 82 +/- 7.2
      microM (mean +/- SE, n = 8), twice that in controls (43 +/- 3.6 microM, n = 12).
      For 7-wk diabetic rats, the IC50 was 75 +/- 2.3 microM (n = 6). Increasing
      internal ADP concentration attenuated ATP-induced inhibition in both controls and
      diabetics. On reducing the internal pH from 7.4 to 6.8, both control and diabetic
      myocytes showed a 1.7-fold increase in the IC50 for ATP inhibition. No
      differences were observed in either intraburst kinetics or unitary conductance of
      single channels from control and diabetic myocytes. In diabetic myocytes, action
      potential duration at 90% repolarization (APD90) was longer and more variable
      than in controls and was significantly shortened by application of the KATP
      channel opener cromakalim (50 microM). Cromakalim scarcely affected APD90 in
      controls. Computer simulation of the longer diabetic APD90 required a lower
      background conductance during the plateau phase in addition to small, measured
      changes in the delayed rectifier current, transient outward current, and ATP
      sensitive K+ current (KATP current, IKATP). The simulations reproduced the
      enhanced sensitivity of the diabetic APD90 to changes in IKATP. These results
      have important implications for cardiac function in diabetics and their treatment
      by sulfonylureas.

PMID- 9755075
TI  - Increased plasma gln and Leu Ra and inappropriately low muscle protein synthesis
      rate in AIDS wasting.
AB  - Muscle protein wasting occurs in human immunodeficiency virus (HIV)-infected
      individuals and is often the initial indication of acquired immunodeficiency
      syndrome (AIDS). Little is known about the alterations in muscle protein
      metabolism that occur with HIV infection. Nine subjects with AIDS wasting (CD4 <
      200/mm3), chronic stable opportunistic infections (OI), and >/=10% weight loss,
      fourteen HIV-infected men and one woman (CD4 > 200/mm3) without wasting or OI
      (asymptomatic), and six HIV-seronegative lean men (control) received a constant
      intravenous infusion of [1-13C]leucine (Leu) and [2-15N]glutamine (Gln). Plasma
      Leu and Gln rate of appearance (Ra), whole body Leu turnover, disposal and
      oxidation rates, and [13C]Leu incorporation rate into mixed muscle protein were
      assessed. Total body muscle mass/fat-free mass was greater in controls (53%) than
      in AIDS wasting (43%; P = 0.04). Fasting whole body proteolysis and synthesis
      rates were increased above control in the HIV+ asymptomatic group and in the AIDS
      wasting group (P = 0. 009). Whole body Leu oxidation rate was greater in the HIV+
      asymptomatic group than in the control and AIDS-wasting groups (P < 0.05).
      Fasting mixed muscle protein synthesis rate was increased in the asymptomatic
      subjects (0.048%/h; P = 0.01) but was similar in AIDS-wasting and control
      subjects (0.035 vs. 0.037%/h). Plasma Gln Ra was increased in AIDS-wasting
      subjects but was similar in control and HIV+ asymptomatic subjects (P < 0.001).
      These findings suggest that AIDS wasting results from 1) a preferential reduction
      in muscle protein, 2) a failure to sustain an elevated rate of mixed muscle
      protein synthesis while whole body protein synthesis is increased, and 3) a
      significant increase in Gln release into the circulation, probably from muscle.
      Several interesting explanations for the increased Gln Ra in AIDS wasting exist.

PMID- 9755076
TI  - Differential regulation of skeletal muscle protein turnover by insulin and IGF-I
      after bacteremia.
AB  - Skeletal muscle catabolism is a characteristic metabolic response to sepsis. We
      investigated the ability of physiological insulin (2 nM) or insulin-like growth
      factor I (IGF-I, 10 nM) concentrations to modify protein metabolism during
      incubation of epitrochlearis 2, 6, or 15 days after injection of live Escherichia
      coli. On days 2 and 6 postinfection, skeletal muscle exhibited an exacerbated
      negative protein balance resulting from both an inhibition in protein synthesis
      (25%) and an enhanced proteolysis (90%) compared with controls. By day 15
      postinfection, protein balance in infected rats was significantly improved
      compared with either day 2 or 6. At this time, protein synthesis was augmented
      and protein degradation was decreased in infected rats relative to day 6. Insulin
      or IGF-I stimulated protein synthesis in muscles from septic and control rats in
      vitro to the same extent at each time point examined. The ability of insulin or
      IGF-I to limit protein degradation was severely blunted 48 h after infection. On
      day 6 postinfection, the effect of insulin or IGF-I to inhibit proteolysis was
      more pronounced than on day 2. Incubation with IGF-I limited proteolysis to a
      greater extent than insulin on both days in infected but not control rats. By day
      15, insulin diminished proteolysis to the same extent as in controls. The results
      suggest that injection of bacteria causes fundamental derangements in protein
      metabolism that persist for days after infection.

PMID- 9755077
TI  - Influence of age, hyperglycemia, leptin, and NPY on islet blood flow in obese
      hyperglycemic mice.
AB  - This study aimed to elucidate possible age-related changes in islet blood
      perfusion in lean and obese C57BL/6 mice. Obese mice aged 1 mo were hyperglycemic
      and hyperinsulinemic and had an increased islet blood flow compared with age
      matched lean mice. This augmented blood flow could be abolished by pretreatment
      with leptin. The islet blood perfusion was, in contrast to this, markedly
      decreased in obese 6- to 7-mo-old animals compared with age-matched lean mice.
      Reversal of hyperglycemia, but not hyperinsulinemia, in these obese mice with
      phlorizin normalized the islet blood flow. Spontaneous reversal of hyperglycemia,
      but not hyperinsulinemia, was seen in the 12-mo-old obese mice. Islet blood
      perfusion in obese mice at this age did not differ compared with lean mice. It is
      suggested that the initial increase in islet blood flow in obese mice is due to
      the leptin deficiency. The subsequent decrease in islet blood perfusion is
      probably caused by the chronic hyperglycemia. The described islet blood flow
      changes may be of importance for impairment of islet function in obese
      hyperglycemic mice.

PMID- 9755078
TI  - Response of skeletal muscle protein synthesis to insulin in suckling pigs
      decreases with development.
AB  - The elevated rate of muscle protein deposition in the neonate is largely due to
      an enhanced stimulation of skeletal muscle protein synthesis by feeding. To
      examine the role of insulin in this response, hyperinsulinemic-euglycemic-amino
      acid clamps were performed in 7- and 26-day-old pigs. Pigs were infused with 0,
      30, 100, or 1,000 ng . kg-0.66 . min-1 of insulin to mimic the plasma insulin
      levels observed under fasted, fed, refed, and supraphysiological conditions,
      respectively. Whole body amino acid disposal was determined from the rate of
      infusion of an amino acid mixture necessary to maintain plasma essential amino
      acid concentrations near their basal fasting levels. A flooding dose of L-[4
      3H]phenylalanine was used to measure skeletal muscle protein synthesis. Whole
      body amino acid disposal increased progressively as the insulin infusion rate
      increased, and this response was greater in 7- than in 26-day-old pigs. Skeletal
      muscle protein synthesis was stimulated by insulin, and this response was maximal
      at a low insulin infusion rate (30 ng . kg-0.66 . min-1). The stimulation of
      muscle protein synthesis by insulin was also greater in 7- than in 26- day-old
      pigs. These data suggest that muscle protein synthesis is more sensitive to
      insulin than whole body amino acid disposal. The results further suggest that
      insulin is a central regulatory factor in the elevated rate of muscle protein
      deposition and the increased response of skeletal muscle protein synthesis to
      feeding in the neonate.

PMID- 9755079
TI  - Dual mode of action of glucose pentaacetates on hormonal secretion from the
      isolated perfused rat pancreas.
AB  - Isolated perfused rat pancreases were exposed, in the presence of 10. 0 mM L
      leucine, to either alpha-D-glucose pentaacetate, beta-L-glucose pentaacetate, or
      unesterified D-glucose, all tested at a 1.7 mM concentration. The pentaacetate
      ester of alpha-D-glucose and, to a lesser extent, that of beta-L-glucose
      stimulated both insulin and somatostatin release, whereas unesterified D-glucose
      failed to do so. In the case of insulin output, the two esters differed from one
      another not solely by the magnitude of the secretory response but also by its
      time course and reversibility. Compared with these data, the most salient
      difference found in the case of somatostatin release consisted of the absence of
      an early secretory peak in response to alpha-D-glucose pentaacetate
      administration and the higher paired ratio between the secretory responses evoked
      by the esters of glucose and by unesterified D-glucose (5.5 mM) administered at
      the end of the experiments. The two esters provoked an initial and short-lived
      stimulation of glucagon secretion, in sharp contrast to the immediate inhibitory
      action of unesterified D-glucose. Thereafter, alpha-D-glucose pentaacetate, but
      not beta-L-glucose pentaacetate, caused inhibition of glucagon release, such an
      effect being reversed when the administration of the ester was halted. These
      findings indicate a dual mode of action of glucose pentaacetate esters on
      hormonal secretion from the endocrine pancreas. The intracellular hydrolysis of
      alpha-D-glucose pentaacetate and subsequent catabolism of its hexose moiety may
      contribute to the early peak-shaped insulin response to this ester, to the
      persistence of a positive secretory effect in B and D cells after cessation of
      its administration, and to the late inhibition of glucagon release. However, a
      direct effect of the esters themselves, by some as-of-yet unidentified coupling
      process, is postulated to account for the stimulation of insulin and somatostatin
      release by beta-L-glucose pentaacetate and for the initial enhancement of
      glucagon secretion provoked by both glucose esters.

PMID- 9755080
TI  - Temporal activation of p70 S6 kinase and Akt1 by insulin: PI 3-kinase-dependent
      and -independent mechanisms.
AB  - Several studies have suggested that activation of p70 ribosomal S6 kinase (p70 S6
      kinase) by insulin may be mediated by the phosphatidylinositol 3-kinase (PI 3
      kinase)-Akt pathway. However, by temporal analysis of the activation of each
      kinase in L6 muscle cells, we report that the activation of the two
      serine/threonine kinases (Akt and p70 S6 kinase) can be dissociated. Insulin
      stimulated p70 S6 kinase in intact cells in two phases. The first phase (5 min)
      of stimulation was fully inhibited by wortmannin (IC50 = 20 nM) and LY-294002
      (full inhibition at 5 microM). After this early inhibition, p70 S6 kinase was
      gradually stimulated by insulin in the presence of 100 nM wortmannin. After 30
      min, the stimulation was 65% of the maximum attained in the absence of
      wortmannin. The IC50 of wortmannin for inhibition of this second phase was
      approximately 150 nM. In contrast, activation of Akt1 by insulin was completely
      inhibited by 100 nM wortmannin at all time points investigated. Inhibition of
      mitogen-activated protein kinase/extracellular signal-regulated protein kinase
      kinase with PD-098059 (10 microM) or treatment with the protein kinase C
      inhibitor bisindolylmaleimide (10 microM) had no effect on the late phase of
      insulin stimulation of p70 S6 kinase. We have previously shown that GLUT-1
      protein synthesis in these cells is stimulated by insulin via the mTOR-p70 S6
      kinase pathway, based on its sensitivity to rapamycin. We therefore investigated
      whether the signals leading to GLUT-1 synthesis correlated with the early or late
      phase of stimulation of p70 S6 kinase. GLUT-1 synthesis was not inhibited by
      wortmannin (100 nM). In summary, insulin activates p70 ribosomal S6 kinase in L6
      muscle cells by two mechanisms, one dependent on and one independent of the
      activation of PI 3-kinase. In addition, activation of Akt1 is fully inhibited by
      wortmannin, suggesting that Akt1 does not participate in the late activation of
      p70 S6 kinase. Wortmannin-sensitive PI 3-kinases and Akt1 are not required for
      insulin stimulation of GLUT-1 protein biosynthesis.

PMID- 9755081
TI  - Smaller differences in total and regional adiposity with age in women who
      regularly perform endurance exercise.
AB  - Our aim was to determine if women who regularly perform endurance exercise
      demonstrate age-related elevations in body mass and adiposity. Ninety-five
      healthy females were studied: premenopausal (n = 28; mean +/- SE age 30 +/- 1 yr)
      and postmenopausal (n = 31; 56 +/- 1 yr) endurance-trained runners and
      premenopausal (n = 17; 29 +/- 1 yr) and postmenopausal (n = 19; 61 +/- 1 yr)
      sedentary controls. In the runners, body mass did not differ across age, but
      percent fat and fat mass were higher (P < 0.05) in the postmenopausal women. The
      age-related difference in total body fat, however, was only approximately 50% as
      great (P < 0.01) as that observed in the sedentary controls due in part to
      smaller age-related differences in central (truncal) fat. The higher fat mass in
      the postmenopausal runners was modestly (inversely) related to both exercise
      volume (r = -0.44, P < 0.01) and maximal oxygen consumption (r = -0.41, P <
      0.01). The present findings provide experimental support for the hypothesis that
      women who regularly engage in vigorous endurance exercise may not gain body
      weight, undergo only a modest increase in total body fat, and do not demonstrate
      a significant elevation in central adiposity with age.

PMID- 9755082
TI  - Effect of fentanyl on morphine levels in the brain in rats receiving
      intracerebroventricular injection of TNF-alpha.
AB  - Fentanyl citrate analgesia attenuates the excess nitrogen excretion in the urine
      and glucose production induced by trauma. On the other hand,
      intracerebroventricular injection of morphine stimulates excretion of stress
      hormones, such as catecholamines and corticosterone. Furthermore, morphine levels
      in the brain are increased during fasting and sepsis. The aims of this study were
      to determine whether intracerebroventricular injection of tumor necrosis factor
      alpha (TNF-alpha) elevates morphine levels in the rat brain and whether
      prophylactic administration of fentanyl blocks metabolic responses induced by
      intracerebroventricular injection of TNF-alpha because of a reduction of morphine
      levels in the brain. Morphine levels in the brain were increased from 648 to
      1,134 fmol/g at 30 min after intracerebroventricular injection of TNF-alpha (P <
      0.05 vs. control). This increase was associated with an increase in stress
      hormones (corticosterone: 416.1 +/- 69.1 ng/ml, P < 0.05 vs. control;
      epinephrine: 3,778.3 +/- 681.3 pg/ml, P < 0.01 vs. control) and an enhancement of
      proteolysis (254.2 +/- 45.7 micromol Leu . kg-1 . h-1, P < 0.01 vs. control) and
      glucose production (7.5 +/- 0. 7 mg . kg-1 . min-1, P < 0.05 vs. control).
      Fentanyl reduced morphine levels in the brain to 624 fmol/g (not significant vs.
      control), resulting in a reduction of stress hormone levels in the plasma and
      blunted metabolic responses. In conclusion, prophylactic administration of
      fentanyl prevented an increase in morphine levels in the brain induced by
      intracerebroventricular injection of TNF-alpha, leading to a reduction in stress
      hormone levels and subsequent metabolic responses.

PMID- 9755083
TI  - Mechanisms of glucose intolerance during triglyceride infusion.
AB  - Lipid infusions may affect glucose tolerance by effects on glucose production or
      utilization. We performed double-labeled oral glucose tolerance tests with and
      without a lipid infusion in eight normal subjects. During the lipid infusion,
      plasma glucose and insulin levels were higher, showing some insulin resistance.
      The increased glucose level was due to a higher total glucose appearance rate,
      partly reproducible by a control infusion of glycerol [saline 1,181 +/- 71 mg .
      kg-1 . 330 min-1 vs. lipid 1,388 +/- 100 (P < 0.05) vs. glycerol 1,276 +/- 126
      (NS)]. The tracer-determined appearance rate of exogenous glucose was higher with
      lipid infusion but was probably overestimated because of higher 13C recycling
      into glucose. Residual systemic glucose production was increased but was
      reproducible by the glycerol infusion. Total glucose disposal was increased. This
      was observed despite a lower stimulation of total glucose oxidation as measured
      by indirect calorimetry, whereas oxidation of exogenous glucose was normal after
      correction for the lipid-induced modification of excretion rate of 13CO2.
      Accordingly, glucose nonoxidative disposal was increased. These moderate
      modifications of glucose metabolism (increased appearance, increased nonoxidative
      disposal, and lower total oxidation) have been reported in starvation-induced or
      spontaneously impaired glucose tolerance. Further impairment, especially
      decreased nonoxidative glucose disposal, seems to be required to produce non
      insulin-dependent diabetes mellitus.

PMID- 9755084
TI  - Effect of Ca2+ and cAMP on capacitance-measured hormone secretion in human GH
      secreting adenoma cells.
AB  - Membrane capacitance (Cm) was measured as an index of exocytosis in human growth
      hormone-secreting adenoma cells using the perforated whole cell, patch-clamp
      technique; the effects of membrane depolarization, growth hormone-releasing
      hormone, and 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) were
      examined. Cm was increased by membrane depolarization to potentials beyond the
      threshold necessary to open voltage-gated Ca2+ channels. These voltage-dependent
      changes in Cm varied as a function of both depolarization amplitude and duration
      and were blocked in the presence of the Ca2+ channel antagonist nitrendipine (10(
      6) M). When membrane potential was clamped at the holding potential (-78 mV),
      voltage-gated Ca2+ channels were closed, and neither application of growth
      hormone-releasing hormone nor 8-BrcAMP affected Cm. However, when these agents
      were applied to depolarized cells, where the voltage-gated Ca2+ channels were
      open, the increases in Cm were augmented. From these data, it was concluded that
      elevation of intracellular cAMP, per se, did not stimulate exocytosis. Rather,
      Ca2+ influx through voltage-gated channels was a prerequisite for cAMP-induced
      exocytosis.

PMID- 9755085
TI  - Regulation of hepatic glutamine metabolism during exercise in the dog.
AB  - The goal of this study was to determine how liver glutamine (Gln) metabolism
      adapts to acute exercise in the 18-h-fasted dogs (n = 7) and in dogs that were
      glycogen depleted by a 42-h fast (n = 8). For this purpose, sampling (carotid
      artery, portal vein, and hepatic vein) and infusion (vena cava) catheters and
      Doppler flow probes (portal vein, hepatic artery) were implanted under general
      anesthesia. At least 16 days later an experiment, consisting of a 120-min
      equilibration period, a 30-min basal sampling period, and a 150-min exercise
      period was performed. At the start of the equilibration period, a constant-rate
      infusion of [5-15N]Gln was initiated. Arterial Gln flux was determined by isotope
      dilution. Gut and liver Gln release into and uptake from the blood were
      calculated by combining stable isotopic and arteriovenous difference methods. The
      results of this study show that 1) in the 18-h-fasted dog, approximately 10% and
      approximately 35% of the basal Gln appearance in arterial blood is due to Gln
      release from the gut and liver, respectively, whereas approximately 30% and
      approximately 25% of the basal Gln disappearance is due to removal by these
      tissues; 2) extending the fast to 42 h does not affect basal arterial Gln flux or
      the contribution of the gut to arterial Gln fluxes but decreases hepatic Gln
      release, causing a greater retention of gluconeogenic carbon by the liver; 3)
      moderate-intensity exercise increases hepatic Gln removal from the blood
      regardless of fast duration but does not affect the hepatic release of Gln; and
      4) Gln plays an important role in channeling nitrogen into the ureagenic pathway
      in the basal state, and this role is increased by approximately 80% in response
      to exercise. These studies illustrate the quantitative importance of the
      splanchnic bed contribution to arterial Gln flux during exercise and the ability
      of the liver to acutely adapt to changes in metabolic requirements induced by the
      combined effects of fasting and exercise.

PMID- 9755086
TI  - Skeletal muscle phosphatidylcholine fatty acids and insulin sensitivity in normal
      humans.
AB  - The fatty acid composition of skeletal muscle membrane phospholipids (PL) is
      known to influence insulin responsiveness in humans. However, the contribution of
      the major PL of the outer (phosphatidylcholine, PC) and inner
      (phosphatidylethanolamine, PE) layers of the sarcolemma to insulin sensitivity is
      not known. Fatty acid composition of PC and PE from biopsies of vastus lateralis
      from 27 normal men and women were correlated with insulin sensitivity determined
      by the hyperinsulinemic euglycemic clamp technique at insulin infusion rates of
      0.4, 1.0, and 10.0 mU . kg-1 . min-1. Significant variation in the half-maximal
      insulin concentration (ED50) was observed in the normal volunteers (range 24.0
      146.0 microU/ml), which correlated directly with fasting plasma insulin (r =
      0.75, P < 0.0001). ED50 was inversely correlated with the degree of membrane
      unsaturation (C20-C22 polyunsaturated fatty acids; r = 0. 58, P < 0.01) and
      directly correlated with fatty acid elongation (ratio of 16:0 to 18:0, r = 0.45,
      P < 0.05) in PC. However, no relationship between fatty acid composition and
      insulin sensitivity was observed in PE (NS). These studies suggest that the fatty
      acid composition of PC may be of particular importance in the relationship
      between fatty acids and insulin sensitivity in normal humans.

PMID- 9755087
TI  - Effects of estrogen and estrous cycle on glucocorticoid and catecholamine
      responses to stress in sheep.
AB  - There have been relatively few studies of the effects of estrogen on hormonal
      responses to stress. We therefore studied changes in ACTH, cortisol,
      norepinephrine (NE), and epinephrine (Epi) after stress induced by a barking dog
      (audiovisual stressor) and insulin-induced hypoglycemia (metabolic stressor) in
      ovariectomized sheep treated with estradiol or placebo and in intact sheep in the
      follicular and luteal phases of the estrous cycle. Both stressors produced acute
      increases in ACTH, cortisol, Epi, and NE. A high physiological dose of estradiol
      significantly reduced the ACTH and cortisol responses to both stressors but did
      not affect Epi and NE responses. Plasma ACTH and cortisol responses to both
      stressors and Epi and NE responses to insulin were lower in the follicular than
      in the luteal phase, but catecholamine responses to the audiovisual stressor did
      not change during the estrous cycle. We conclude that in sheep, estrogen
      attenuates glucocorticoid responses to stress and that hormonal changes during
      the estrous cycle affect glucocorticoid responses to both metabolic and
      audiovisual stressors and catecholamine responses to a metabolic stressor.

PMID- 9755088
TI  - A modified high-fat diet induces insulin resistance in rat skeletal muscle but
      not adipocytes.
AB  - We hypothesized that variation in dietary fatty acid composition in rats fed a
      high-fat diet had tissue-specific effects on glucose uptake sufficient to
      maintain normal glucose tolerance. Rats were fed one of three diets for 3 wk. The
      isocaloric high-fat-mixed oil (HF-mixed) diet and the high-fat-safflower oil (HF
      saff) diet both provided 60% kcal fat, but fat composition differed [HF-mixed =
      saturated, polyunsaturated (n-3 and n-6), and monounsaturated fatty acids; HF
      saff = polyunsaturated fatty acids (mainly n-6)]. The control diet was high
      carbohydrate (HCHO, 10% kcal fat). Insulin-stimulated 3-O-methylglucose uptake
      into perfused hindlimb muscles was reduced in rats fed HF-saff and HF-mixed diets
      compared with those fed HCHO diet (P < 0.02). Basal uptake increased in HF-saff-
      and HF-mixed-fed rats vs. HCHO-fed rats (P < 0.04). In adipocytes, HF-saff
      feeding decreased 2-deoxyglucose uptake vs. HF-mixed feeding and HCHO feeding (P
      < 0.05), but 2-deoxyglucose uptake in HF-mixed-fed rats did not differ from that
      in HCHO-fed rats (P > 0.05). Glucose tolerance was significantly reduced in HF
      saff-fed rats but was unaffected by the HF-mixed diet. Therefore, in skeletal
      muscle of rats, 1) feeding a diet high in fat induces a reduction in insulin
      stimulated glucose uptake but 2) provides an increase in basal glucose uptake. In
      contrast, 3) in adipocytes, insulin-stimulated glucose transport is reduced only
      when the high-fat diet is high in n-6 polyunsaturated fatty acids but not when
      fat comes from these mixed sources. Glucose intolerance becomes evident when
      insulin resistance is seen in multiple tissues.

PMID- 9755089
TI  - Dopaminergic control of angiotensin II-induced vasopressin secretion in vitro.
AB  - Because dopamine influences arginine vasopressin (AVP) release, the present
      studies were designed to ascertain the dopamine receptor subtype that potentiates
      angiotensin II-induced AVP secretion in cultured hypothalamo-neurohypophysial
      explants. Dopamine (a nonselective D1/D2 agonist), apomorphine (a D2 >> D1
      agonist), and SKF-38393 (a selective D1 agonist) dose dependently increased AVP
      secretion. Maximal AVP release was observed with 5 microM dopamine, 307 +/- 66% .
      explant-1 . h-1, 1 microM SKF-38393, 369 +/- 41% . explant-1 . h-1, and 0.1
      microM apomorphine, 374 +/- 67% . explant-1 . h-1. Selective D1 antagonism with 1
      microM SCH-23390 blocked AVP secretion to values no different from basal.
      Domperidone (D2 antagonist), phenoxybenzamine (nonselective adrenergic
      antagonist), and prazosin (alpha1-antagonist) failed to prevent release. D1
      antagonism also prevented AVP secretion to 1 microM angiotensin II [angiotensin
      II, 422 +/- 87% . explant-1 . h-1 vs. angiotensin II plus SCH-23390, 169 +/- 28%
      . explant-1 . h-1 (P < 0.05)], but D2 and alpha1-adrenergic blockade did not. In
      contrast, AT1 receptor inhibition with 0.5 microM losartan blocked angiotensin II
      but not dopamine-induced AVP release. AT2 antagonism had no effect. Although
      subthreshold doses of the agonists did not increase AVP secretion (0. 05 microM
      dopamine, 133 +/- 44% . explant-1 . h-1; 0.01 microM SKF-38393, 116 +/- 26% .
      explant-1 . h-1;and 0.001 microM angiotensin II, 104 +/- 29% . explant-1 . h-1 ),
      the combination of dopamine and angiotensin II provoked a significant rise in AVP
      [420 +/- 83% . explant-1 . h-1 (P < 0.01)]. Similar results were observed with
      SKF-38393 and angiotensin II, and the AVP response was blocked to basal levels by
      either D1 or AT1 antagonism. These findings support a role for D1 receptor
      activation to increase AVP release and mediate angiotensin II-induced AVP release
      within the hypothalamo-neurohypophysial system. The data also suggest that the
      combined subthreshold stimulation of receptors that use distinct intracellular
      pathways can prompt substantial AVP release.

PMID- 9755090
TI  - Systemic administration of amylin increases bone mass, linear growth, and
      adiposity in adult male mice.
AB  - Amylin is a peptide hormone cosecreted with insulin from the pancreatic beta
      cells that can act as an osteoblast mitogen and as an inhibitor of bone
      resorption. The effects on bone of its systemic administration are uncertain. The
      present study addresses this question in adult male mice that were given daily
      subcutaneous injections of amylin (10.5 microgram) or vehicle (n = 20 in each
      group) for 4 wk. Histomorphometric indices of bone formation increased 30-100% in
      the amylin-treated group, whereas resorption indices were reduced by
      approximately 70% (P < 0.005 for all indices). Total bone volume in the proximal
      tibia was 13.5 +/- 1.4% in control animals and 23.0 +/- 2.0% in those receiving
      amylin (P = 0.0005). Cortical width, tibial growth plate width, tibial length,
      body weight, and fat mass were all increased in the amylin-treated group. It is
      concluded that systemic administration of amylin increases skeletal mass and
      linear bone growth. This peptide has potential as a therapy for osteoporosis if
      its bone effects can be dissociated from those on soft tissue mass.

PMID- 9755091
TI  - Intrinsic mineralization defect in Hyp mouse osteoblasts.
AB  - X-linked hypophosphatemia (XLH) is caused by inactivating mutations of PEX, an
      endopeptidase of uncertain function. This defect is shared by Hyp mice, the
      murine homologue of the human disease, in which a 3' Pex deletion has been
      documented. In the present study, we report that immortalized osteoblasts derived
      from the simian virus 40 (SV40) transgenic Hyp mouse (TMOb-Hyp) have an impaired
      capacity to mineralize extracellular matrix in vitro. Compared with immortalized
      osteoblasts from the SV40 transgenic normal mouse (TMOb-Nl), osteoblast cultures
      from the SV40 Hyp mouse exhibit diminished 45Ca accumulation into extracellular
      matrix (37 +/- 6 vs. 1,484 +/- 68 counts . min-1 . microgram protein-1) and
      reduced formation of mineralization nodules. Moreover, in coculture experiments,
      we found evidence that osteoblasts from the SV40 Hyp mouse produce a diffusible
      factor that blocks mineralization of extracellular matrix in normal osteoblasts.
      Our findings indicate that abnormal PEX in osteoblasts is associated with the
      accumulation of a factor(s) that inhibits mineralization of extracellular matrix
      in vitro.

PMID- 9755092
TI  - Splanchnic retention of intraduodenal and intrajejunal glucose in healthy adults.
AB  - Estimates of the spanchnic retention and appearance in the systemic circulation
      of orally administered glucose vary among laboratories even after recently
      identified sources of error have been accounted for [Livesey, G., P. D. G.
      Wilson, J. R. Dainty, J. C. Brown, R. M. Faulks, M. A. Roe, T. A. Newman, J.
      Eagles, F. A. Mellon, and R. Greenwood. Am. J. Physiol. 275 (Endocrinol. Metab.
      38): E717-E728, 1998]. We questioned whether, in healthy humans, D-glucose
      delivered intraluminally to the midjejunum appeared systemically as extensively
      as that delivered intraduodenally. Subjects were infused over a period of 90 min
      with 50 g of glucose in 1 liter of isotonic saline (incorporating 0.5 g D
      [13C6]glucose) per 70 kg of body weight. Infusions were via enteral tubes
      terminating approximately 15 and 100 cm postpylorus. The systemic appearance of
      glucose was monitored by means of a primed-continuous intravenous infusion of D
      [6,6-2H2]glucose. Whereas 98 +/- 2% (n = 7) of the duodenally infused glucose
      appeared in the systemic circulation, only 35 +/- 9% (n = 7) of midjejunally
      infused glucose did so, implying that 65 +/- 9% was retained in the splanchnic
      bed. Either glucose was less efficiently absorbed at the midintestinal site or
      hepatic glucose sequestration was increased 10-fold, or both. The proximal
      intestine plays a key role in the delivery of glucose to the systemic
      circulation, and the distal intestine potentially delivers more glucose to the
      liver.

PMID- 9755093
TI  - Simultaneous time-varying systemic appearance of oral and hepatic glucose in
      adults monitored with stable isotopes.
AB  - The rates (and extent) of appearance of glucose in arterialized plasma from an
      oral glucose load and from liver (RaO, RaH) can be estimated in humans using
      radioisotopes, but estimates vary among laboratories. We investigated the use of
      stable isotopes and undertook 22 primed intravenous infusions of D-[6,6
      2H2]glucose with an oral load including D-[13C6]glucose in healthy humans. The
      effective glucose pool volume (VS) had a lower limit of 230 ml/kg body weight
      (cf. 130 ml/kg commonly assumed). This VS in Steele's one-compartment model of
      glucose kinetics gave a systemic appearance from a 50-g oral glucose load per 70
      kg body weight of 96 +/- 3% of that ingested, which compared with a theoretical
      value of approximately 95%. Mari's two-compartment model gave 100 +/- 3%. The two
      models gave practically identical RaO and RaH at each point in time and a plateau
      in the cumulative RaO when absorption was complete. Less than 3% of 13C was
      recycled to [13C3]glucose, suggesting that recycling errors were practically
      negligible in this study. Causes of variation among laboratories are identified.
      We conclude that stable isotopes provide a reliable and safe alternative to
      radioactive isotopes in these studies.

PMID- 9755094
TI  - Lactate clamp: a method to measure lactate utilization in vivo.
AB  - A lactate clamp method has been developed to quantify the whole body lactate
      utilization in conscious, unstressed rats. Dichloroacetate (DCA), a known lactate
      utilization enhancer, was used to validate the method. Fasting blood lactate
      concentrations before the clamps were identical for DCA-treated (1 mmol/kg) and
      control groups (1.65 +/- 0.37 vs. 1.65 +/- 0.19 mM). The animals received a
      primed continuous lactate infusion for 90 min at variable rates to clamp the
      blood lactate concentration at 2 mM. The steady-state (60-90 min) lactate
      infusion rate, which represents the whole body lactate utilization in DCA-treated
      animals, was 144% higher than that in the control animals (13.2 +/- 1.0 vs. 5.4
      +/- 1.1 mg . kg-1 . min-1; P < 0.001). The markedly increased lactate infusion
      rate indicates an enhanced lactate flux by DCA. To determine whether the
      increased lactate infusion by DCA reflected reduced endogenous lactate
      production, lactate production was measured. The results indicate that endogenous
      lactate production was not affected by DCA. In conclusion, the lactate clamp
      provides a sensitive and reliable method to assess lactate utilization in vivo, a
      dynamic measurement that may not be clearly demonstrated by blood lactate
      concentrations per se.

PMID- 9755095
TI  - Regulation of extracellular matrix synthesis by TNF-alpha and TGF-beta1 in type
      II cells exposed to coal dust.
AB  - Type II pulmonary epithelial cells respond to anthracite coal dust PSOC 867 with
      increased synthesis of extracellular matrix (ECM) components. Alveolar
      macrophages modulate this response by pathways that may involve soluble
      mediators, including tumor necrosis factor-alpha (TNF-alpha) or transforming
      growth factor-beta1 (TGF-beta1). The effects of TNF-alpha (10 ng/ml) and/or TGF
      beta1 (2 ng/ml) were thus investigated in dust-exposed primary type II cell
      cultures. In control day 1 or day 3 cultures, TNF-alpha and/or TGF-beta1 had
      little or no effect on the synthesis of type II cellular proteins, independent of
      whether the cells were exposed to dust. With PSOC 867 exposure, where ECM protein
      synthesis is elevated, TNF-alpha and TGF-beta1 further increased both the
      absolute and relative rates of ECM synthesis on day 3 but had little effect on
      day 1. Each mediator increased expression of fibronectin mRNA, as well as of ECM
      fibronectin content, in a manner qualitatively similar to their effects on
      synthesis. Thus TNF-alpha and TGF-beta1 modulate both ECM synthesis and
      fibronectin content in coal dust-exposed type II cell cultures.

PMID- 9755096
TI  - C-type natriuretic peptide expression and pulmonary vasodilation in hypoxia
      adapted rats.
AB  - Atrial and brain natriuretic peptides (ANP and BNP, respectively) are potent
      pulmonary vasodilators that are upregulated in hypoxia-adapted rats and may
      protect against hypoxic pulmonary hypertension. To test the hypothesis that C
      type natriuretic peptide (CNP) also modulates pulmonary vascular responses to
      hypoxia, we compared the vasodilator effect of CNP with that of ANP on pulmonary
      arterial rings, thoracic aortic rings, and isolated perfused lungs obtained from
      normoxic and hypoxia-adapted rats. We also measured CNP and ANP levels in heart,
      lung, brain, and plasma in normoxic and hypoxia-adapted rats. Steady-state CNP
      mRNA levels were quantified in the same organs by relative RT-PCR. CNP was a less
      potent vasodilator than ANP in preconstricted thoracic aortic and pulmonary
      arterial rings and in isolated lungs from normoxic and hypoxia-adapted rats.
      Chronic hypoxia increased plasma CNP (15 +/- 2 vs. 6 +/- 1 pg/ml; P < 0.05) and
      decreased CNP in the right atrium (35 +/- 14 vs. 65 +/- 17 pg/mg protein; P <
      0.05) and in the lung (3 +/- 1 vs. 14 +/- 3 pg/mg protein; P < 0.05) but had no
      effect on CNP in brain or right ventricle. Chronic hypoxia increased ANP levels
      fivefold in the right ventricle (49 +/- 5 vs. 11 +/- 2 pg/mg protein; P < 0.05)
      but had no effect on ANP in lung or brain. There was a trend toward decreased ANP
      levels in the right atrium (2,009 +/- 323 vs. 2,934 +/- 397 pg/mg protein; P =
      not significant). No differences in CNP transcript levels were observed between
      the two groups of rats except that the right atrial CNP mRNA levels were lower in
      hypoxia-adapted rats. We conclude that CNP is a less potent pulmonary vasodilator
      than ANP in normoxic and hypoxia-adapted rats and that hypoxia raises circulating
      CNP levels without increasing cardiopulmonary CNP expression. These findings
      suggest that CNP may be less important than ANP or BNP in protecting against
      hypoxic pulmonary hypertension in rats.

PMID- 9755097
TI  - Human surfactant proteins A1 and A2 are differentially regulated during
      development and by soluble factors.
AB  - An RT-PCR method for the relative quantitation of the mRNAs for human surfactant
      protein (SP) A1 and SP-A2 was developed, verified, and then utilized to determine
      the relative levels of these mRNAs in fetal and adult lung samples in vivo, as
      well as in cultured human fetal lung explants and H441 cells. For the cultured
      tissue and cells, we assessed the effects of a variety of soluble factors known
      to modulate total SP-A. Comprehensive analysis revealed many significant
      findings, including the following: both mRNAs were expressed as early as 15 wk of
      gestation; throughout midgestation, SP-A1 was present at higher levels than SP
      A2, with an average ratio of 30:1. In the adult lung, SP-A1 mRNA was present at
      lower levels than SP-A2, with a ratio of 0.4:1, whereas in H441 cells, the ratio
      was 0.85:1. In fetal lung cultured for 4 days, both mRNAs increased, with a
      greater increase in SP-A2 (97-fold) than in SP-A1 (15-fold), resulting in a final
      ratio of 4:1. Differential regulation was demonstrated for 8-(4-chlorophenylthio)
      cAMP, interferon (IFN)-gamma, tumor necrosis factor-alpha, and transforming
      growth factor (TGF)-beta in the human fetal lung explant system, with SP-A2 being
      more affected, and for IFN-gamma and TGF-beta in the H441 cells, where SP-A1
      showed greater regulation. Of the soluble factors tested, IFN-gamma and TGF-beta
      had the most potent and consistent effects in both systems.

PMID- 9755098
TI  - Osmotic stress induces both secretion and apoptosis in rat alveolar type II
      cells.
AB  - The aim of this study was to analyze the effects of osmotic shock and
      secretagogues such as ATP and 12-O-tetradecanoylphorbol 13-acetate (TPA) on
      various intracellular signaling pathways in primary cultures of alveolar type II
      cells and examine their potential role in regulating events such as secretion and
      apoptosis in these cells. Sorbitol-induced osmotic stress caused the sustained
      release of [3H]phosphatidylcholine ([3H]PC) from primary cultures of rat alveolar
      type II cells prelabeled with [3H]choline chloride. This release was not
      dependent on protein kinase C because downregulation of the major protein kinase
      C isoforms (alpha, betaII, delta, and eta) expressed in alveolar type II cells
      had no effect on [3H]PC secretion. Sorbitol, as well as the known secretagogues
      TPA and ATP, activated extracellular signal-regulated kinase. Although an
      inhibitor of the extracellular signal-regulated kinase cascade, PD-98059, blocked
      this activation, it had no effect on the release of [3H]PC. Sorbitol and
      ultraviolet C radiation, but not TPA or ATP, were also found to activate both p38
      and stress-activated protein kinase/c-Jun NH2-terminal kinase. Furthermore, both
      sorbitol and ultraviolet C radiation induced apoptosis in alveolar type II cells
      as demonstrated by Hoechst 33258 staining of the condensed nuclei, the generation
      of DNA ladders, and the activation of caspases. The data indicate that multiple
      signaling pathways are activated by traditional secretagogues such as TPA and ATP
      and by cellular stresses such as osmotic shock and that these may be involved in
      regulating secretory and apoptotic events in alveolar type II cells.

PMID- 9755100
TI  - Alveolar type II-like cells release G-CSF as neutrophil chemotactic activity.
AB  - We evaluated the potential of A549 cells, an alveolar type II epithelial cell
      line, to release granulocyte colony-stimulating factor (G-CSF), in addition to
      interleukin (IL)-8 and leukotriene B4, as neutrophil chemotactic activity (NCA).
      Human recombinant IL-1beta stimulated A549 cells to release NCA in a time- and
      dose-dependent fashion. The released NCA was blocked by mouse anti-human G-CSF
      polyclonal antibody. Molecular-sieve column chromatography revealed that IL-1beta
      induced the release of a 19- to 20-kDa chemotactic mass that was inhibited by
      anti-human G-CSF antibody. IL-1beta stimulated the release of G-CSF in a dose
      dependent fashion, but the time-dependent profile of G-CSF showed that the
      concentration of G-CSF declined after 48 h. Tumor necrosis factor (TNF)-alpha,
      Escherichia coli lipopolysaccharide (LPS), and bradykinin (BK) stimulated A549
      cells to release NCA that was inhibited by anti-G-CSF antibody. The release of G
      CSF in response to TNF-alpha, LPS, and BK was significantly increased. The
      similar concentrations of human recombinant G-CSF (10-1,000 pg/ml) as in the
      supernatant fluid induced neutrophil chemotaxis. G-CSF mRNA was expressed time
      and dose dependently at 4 h and declined after 4 h in response to IL-1beta as
      evaluated by RT-PCR. The expression of G-CSF mRNA was also observed by TNF-alpha,
      LPS, and BK stimulation. These data suggest that type II alveolar epithelial
      cells may produce G-CSF as NCA and may participate in the regulation of leukocyte
      extravasation.

PMID- 9755099
TI  - Surfactant protein A inhibits T cell proliferation via its collagen-like tail and
      a 210-kDa receptor.
AB  - Investigation of possible mechanisms to describe the hyporesponsiveness of
      pulmonary leukocytes has led to the study of pulmonary surfactant and its
      constituents as immune suppressive agents. Pulmonary surfactant is a phospholipid
      protein mixture that reduces surface tension in the lung and prevents collapse of
      the alveoli. The most abundant protein in this mixture is a hydrophilic molecule
      termed surfactant-associated protein A (SP-A). Previously, we showed that bovine
      (b) SP-A can inhibit human T lymphocyte proliferation and interleukin-2
      production in vitro. Results presented in this investigation showed that
      different sources of human SP-A and bSP-A as well as recombinant rat SP-A
      inhibited human T lymphocyte proliferation in a dose-dependent manner. A
      structurally similar collagenous protein, C1q, did not block the in vitro
      inhibitory action of SP-A. The addition of large concentrations of mannan to SP-A
      treated cultures also did not disrupt inhibition, suggesting that the effect is
      not mediated by the carbohydrate recognition domain of SP-A. Use of recombinant
      mutant SP-As revealed that a 36-amino acid Arg-Gly-Asp (RGD) motif-containing
      span of the collagen-like domain was responsible for the inhibition of T cell
      proliferation. A polyclonal antiserum directed against an SP-A receptor (SP-R210)
      completely blocked the inhibition of T cell proliferation by SP-A. These results
      emphasize a potential role for SP-A in dampening lymphocyte responses to
      exogenous stimuli. The data also provide further support for the concept that SP
      A maintains a balance between the clearance of inhaled pathogens and protection
      against collateral immune-mediated damage.

PMID- 9755101
TI  - Phosphodiesterase expression in human epithelial cells.
AB  - Epithelial cells play a critical role in airway inflammation and have the
      capacity to produce many inflammatory mediators, including bioactive lipids and
      proinflammatory cytokines. Intracellular levels of cAMP and cGMP are important in
      the control of inflammatory cell function. These cyclic nucleotides are
      inactivated via a family of phosphodiesterase (PDE) enzymes, providing a possible
      site for drug intervention in chronic inflammatory conditions. We studied the
      expression of PDE activity in an epithelial cell line (A549) and in primary human
      airway epithelial cells (HAECs). We measured PDE function using specific
      inhibitors to identify the PDE families present and used RT-PCR to elucidate the
      expression of PDE isogenes. Both A549 cells and HAECs predominantly expressed
      PDE4 activity, with lesser PDE1, PDE3, and PDE5 activity. RT-PCR identified
      HSPDE4A5 and HSPDE4D3 together with HSPDE7. Inhibition of PDE4 and PDE3 reduced
      secretion by these cells. Epithelial PDE may be an important target for PDE4
      inhibitors in the development of the control of asthmatic inflammation,
      particularly when delivered via the inhaled route.

PMID- 9755102
TI  - Sulfation of extracellular matrices modifies growth factor effects on type II
      cells on laminin substrata.
AB  - The alveolar basement membrane contains a variety of extracellular matrix (ECM)
      molecules, including laminin and sulfated glycosaminoglycans of proteoglycans.
      These mixtures exist within microdomains of differing levels of sulfate, which
      may specifically interact to be key determinants of the known capacity of the
      type II cell to respond to certain growth factors. Isolated type II cells were
      exposed to either acidic fibroblast growth factor (FGF-1), basic fibroblast
      growth factor (FGF-2), or keratinocyte growth factor (KGF; FGF-7) on culture
      wells precoated with laminin alone or in combination with chondroitin sulfate
      (CS), high-molecular-weight heparin, or their desulfated forms. Desulfated
      heparin significantly elevated FGF-1- and FGF-2-stimulated DNA synthesis, whereas
      desulfated CS and N-desulfated heparin elevated FGF-7-stimulated DNA synthesis by
      type II cells on laminin substrata. When FGF-1 was mixed into the various test
      matrix substrata, DNA synthesis was significantly increased in all cases. These
      results demonstrated that decreased levels of sulfate in ECM substrata act to
      upregulate responses to heparin-binding growth factors by alveolar epithelial
      cells on laminin substrata.

PMID- 9755103
TI  - O2-sensitive K+ channels in neuroepithelial body-derived small cell carcinoma
      cells of the human lung.
AB  - Neuroepithelial bodies act as airway O2 sensors, but studies of their activity at
      the cellular level have been severely limited because they are present at such a
      low density in lung tissue. Small cell lung carcinoma (SCLC) cells are believed
      to be derived from neuroepithelial body cells and may represent a model system
      for investigating the mechanisms of airway chemoreception. Here we have used the
      whole cell patch-clamp technique to investigate the effects of acute hypoxia on
      voltage-gated ionic currents and membrane potential in H-146 SCLC cells. Step
      depolarizations evoked transient inward currents due to activation of Na+ and
      Ca2+ channels, followed by outward K+ currents. K+ currents were partially
      inhibited by 200 microM Cd2+ (indicative of the presence of a Ca2+-dependent
      component of the K+ current) and were inhibited by tetraethylammonium (TEA) in a
      concentration-dependent manner, although even at 100 mM TEA, a residual K+
      current could be detected. Hypoxia (PO2 15-20 mmHg) caused a reversible
      inhibition of outward K+ currents without affecting inward currents. Inhibition
      by hypoxia was also observed in the presence of Cd2+. Hypoxia and TEA caused
      membrane depolarization in H-146 cells, and their effects appeared additive.
      These findings indicate that H-146 cells possess O2-sensitive, Ca2+-independent
      K+ channels that can influence cell membrane potential. SCLC cells may,
      therefore, represent a good model for investigating the mechanisms underlying O2
      sensing by airway chemoreceptor cells.

PMID- 9755104
TI  - Nitric oxide inhibits lipopolysaccharide-induced apoptosis in pulmonary artery
      endothelial cells.
AB  - Our group recently reported that cultured sheep pulmonary artery endothelial
      cells (SPAECs) became resistant to lipopolysaccharide (LPS)-induced apoptosis
      several days after constitutive synthesis of nitric oxide (NO) after adenoviral
      (Ad) transfer of inducible NO synthase (iNOS) or exposure to the NO donor S
      nitroso-N-acetylpenicillamine (SNAP) (E. Tzeng, Y.-M. Kim, B. R. Pitt, A.
      Lizonova, I. Kovesdi, and T. R. Billiar. Surgery 122: 255-263, 1997). In the
      present study, we confirmed this observation by establishing stable transfectants
      after retroviral gene transfer [replication-deficient retrovirus (DFG)] of human
      iNOS (DFG-iNOS) SPAECs and then used all three approaches (Ad, DFG, and SNAP) to
      determine underlying mechanisms of this phenomenon. Continuous endogenous
      production of NO in itself did not cause apoptosis as assessed by phase-contrast
      microscopy, nuclear morphology, and internucleosomal DNA fragmentation. Prolonged
      (72-96 h) synthesis of NO, however, after DFG- or replication-deficient
      adenovirus (Ad. CMV)-iNOS or SNAP (100 microM, 96 h) inhibited LPS-induced
      apoptosis. The kinetics of such protection suggested that NO may be inducing
      other gene products. Ad-mediated transfer of manganese superoxide dismutase
      (MnSOD) decreased the sensitivity of wild-type SPAECs to LPS-induced apoptosis.
      MnSOD, however, was not induced in an NG-monomethyl-L-arginine (L-NMMA)-sensitive
      time-dependent fashion after Ad.CMV-iNOS. Other inducible genes that may be
      affected by NO and that may protect against potential oxidant-mediated LPS
      induced apoptosis including 70-kDa heat shock protein, heme oxygenase-1,
      metallothionein, and Bcl-2 also were not elevated in an L-NMMA-sensitive, time
      dependent fashion. Although the candidate gene product underlying NO-induced
      protection remains unclear, we did note that prolonged synthesis of NO inhibited
      LPS-induced activation of an interleukin-1beta-converting enzyme-like cysteine
      protease (cysteine protease protein-32-like) in a dithiothreitol-sensitive
      fashion, suggesting that S-nitrosylation of an important downstream target of
      convergence of apoptotic signals may contribute to the sensitivity of SPAECs to
      LPS.

PMID- 9755105
TI  - ET-1 modulates KCa-channel activity and arterial tension in normoxic and hypoxic
      human pulmonary vasculature.
AB  - The molecular mechanisms by which endothelin (ET)-1 induces pulmonary
      hypertension are poorly understood. We investigated the effects of ET-1 on
      outward K+ currents of normoxic and chronically hypoxic human pulmonary arterial
      (PA) smooth muscle cells (HPSMCs). In normoxic HPSMCs, ET-1 has dual effects. In
      intact cells, 5 nM ET-1 activates the large-conductance and Ca2+-activated K+
      (KCa)-channel current [IK(Ca)] by increasing intracellular Ca2+ concentration,
      whereas it directly inhibits IK(Ca) in isolated membrane patches. At a higher
      concentration (10 nM), ET-1-induced IK(Ca) inhibition predominates. In hypoxic
      HPSMCs, ET-1 at 5 nM significantly reduces IK(Ca). The ETA-receptor antagonist BQ
      123 reverses the ET-1-induced decrease in IK(Ca). Chronic BQ-123 treatment also
      prevents the hypoxia-induced decrease in IK(Ca). In PA rings obtained from human
      organ donors, ET-1 causes a concentration-dependent increase in tension. The ET-1
      mediated increase in tension is reversed by a KCa-channel agonist. The increase
      in tension at the highest concentration studied (9 nM) was more pronounced in PA
      rings obtained from patients with chronic obstructive pulmonary disease. These
      results imply that an ET-1-induced decrease in IK(Ca) contributes to chronic
      hypoxia-induced pulmonary hypertension.

PMID- 9755106
TI  - Hydrolysis of surfactant-associated phosphatidylcholine by mammalian secretory
      phospholipases A2.
AB  - Hydrolysis of surfactant-associated phospholipids by secretory phospholipases A2
      is an important potential mechanism for surfactant dysfunction in inflammatory
      lung diseases. In these conditions, airway secretory phospholipase A2 (sPLA2)
      activity is increased, but the type of sPLA2 and its impact on surfactant
      function are not well understood. We examined in vitro the effect of multiple
      secretory phospholipases A2 on surfactant, including their ability to 1) release
      free fatty acids, 2) release lysophospholipids, and 3) increase the minimum
      surface tension (gammamin) on a pulsating bubble surfactometer. Natural porcine
      surfactant and Survanta were exposed to mammalian group I (recombinant porcine
      pancreatic) and group II (recombinant human) secretory phospholipases A2. Our
      results demonstrate that mammalian group I sPLA2 hydrolyzes phosphatidylcholine
      (PC), producing free fatty acids and lysophosphatidylcholine, and increases
      gammamin. In contrast, mammalian group II sPLA2 demonstrates limited hydrolysis
      of PC and does not increase gammamin. Group I and group II secretory
      phospholipases A2 from snake venom hydrolyze PC and inhibit surfactant function.
      In summary, mammalian secretory phospholipases A2 from groups I and II differ
      significantly from each other and from snake venom in their ability to hydrolyze
      surfactant-associated PC.

PMID- 9755107
TI  - Role of G proteins in agonist-induced Ca2+ sensitization of tracheal smooth
      muscle.
AB  - Increased sensitivity to intracellular Ca2+ concentration ([Ca2+]) is an
      important mechanism for agonist-induced contraction of airway smooth muscle, but
      the signal transduction pathways involved are uncertain. We studied Ca2+
      sensitization with acetylcholine (ACh) and endothelin (ET)-1 in porcine tracheal
      smooth muscle by measuring contractions at a constant [Ca2+] in strips
      permeabilized with alpha-toxin or beta-escin. The peptide inhibitor G protein
      antagonist 2A (GP Ant-2A), which has selectivity for Gq over Gi, inhibited
      contractile responses to ET-1, ACh, and guanosine 5'-O-(3-thiotriphosphate)
      (GTPgammaS), but the proportional inhibition of ACh responses was less than that
      of ET-1. Pretreatment with pertussis toxin reduced ACh contractions but had no
      effect on those of ET-1 or GTPgammaS. Clostridium botulinum C3 exoenzyme, which
      inactivates Rho family monomeric G proteins, caused similar reductions in
      contractile responses to ACh, ET-1, and GTPgammaS. Farnesyltransferase
      inhibition, which inhibits Ras G proteins, reduced responses to ET-1. We conclude
      that the heterotrimeric G proteins Gq and Gi both contribute to Ca2+
      sensitization by ACh, whereas ET-1 responses involve Gq but not Gi. Both Gq and
      Gi pathways likely involve Rho family small G proteins. A Ras-mediated pathway
      also contributes to Ca2+ sensitization by ET-1 in airway smooth muscle.

PMID- 9755108
TI  - Involvement of cytochrome P-450 enzyme activity in the control of microvascular
      permeability in canine lung.
AB  - Products of cytochrome P-450 enzymes may play a role in capacitative Ca2+ entry
      in endothelial cells, which can promote a rise in vascular permeability.
      Thapsigargin (150 nM) stimulated capacitative Ca2+ entry and increased the
      capillary filtration coefficient (Kf,c) in isolated normal canine lung lobes.
      Pretreatment of the lobes with cytochrome P-450 inhibitors clotrimazole (10
      microM) or 17-octadecynoic acid (5 microM) abolished the thapsigargin-induced
      increases in Kf,c. Because clotrimazole also blocks Ca2+-activated K+ channels,
      the K+-channel blocker tetraethylammonium (10 mM) was used to ensure that
      permeability was not influenced by this mechanism. Tetraethylammonium did not
      affect thapsigargin-induced permeability. The effects of the cytochrome P-450
      arachidonic acid metabolite 5,6-epoxyeicosatrienoic acid (EET) were also
      investigated in lobes taken from control dogs and dogs with pacing-induced heart
      failure (paced at 245 beats/min for 4 wk). 5,6-EET (10 microM) significantly
      increased Kf,c in lobes from the control but not from the paced animals. We
      conclude that cytochrome P-450 metabolites are involved in mediating
      microvascular permeability in normal canine lungs, but an absence of 5,6-EET
      after heart failure does not explain the resistance of lungs from these animals
      to permeability changes.

PMID- 9755109
TI  - O2-induced ENaC expression is associated with NF-kappaB activation and blocked by
      superoxide scavenger.
AB  - Cultured rat fetal distal lung epithelial cells (FDLEs), when switched from fetal
      (3%) to postnatal (21%) O2 concentrations, have increased epithelial Na+ channel
      (ENaC) mRNA levels and amiloride-sensitive Na+ transport [O. Pitkanen, A. K.
      Tanswell, G. Downey, and H. O'Brodovich. Am. J. Physiol. 270 (Lung Cell. Mol.
      Physiol. 14): L1060-L1066, 1996]. The mechanisms by which O2 mediates these
      effects are unknown. After isolation, FDLEs were kept at 3% O2 overnight, then
      switched to 21% O2 (3-21% O2 group) or maintained at 3% O2 (3-3% O2 group) for 48
      h. The amiloride-sensitive short-circuit current (Isc) in the 3-21% O2 group was
      double that in the 3-3% O2 group. Amiloride-sensitive Isc could not be induced by
      medium conditioned by 21% O2-exposed FDLEs but was reversed by returning the
      cells to 3% O2. Neither the cyclooxygenase inhibitor ibuprofen, liposome
      encapsulated catalase, nor hydroperoxide scavengers (U-74389G or Trolox) blocked
      the O2-induced amiloride-sensitive Isc. In contrast, the cell-permeable
      superoxide scavenger tetramethylpiperidine-N-oxyl (TEMPO) eliminated the O2
      induced increases in amiloride-sensitive Isc and ENaC mRNA levels. The switch
      from 3 to 21% O2 induced the transcription factor nuclear factor-kappaB, which
      could also be blocked by TEMPO. We conclude that 1) the O2-induced increase in
      amiloride-sensitive Isc is reversible and 2) the O2-induced increase in amiloride
      sensitive Isc and ENaC mRNA levels is associated with activation of nuclear
      factor-kappaB and may be mediated, at least in part, by superoxide.

PMID- 9755110
TI  - Tobacco smoke induces both apoptosis and necrosis in mammalian cells:
      differential effects of HSP70.
AB  - Tobacco smoke (TS) has been implicated as a major risk factor in human pulmonary
      diseases including cancer. In this study, we used TS as a model of oxidative
      stress. TS-mediated oxidative stress has been shown to induce protein oxidation,
      DNA damage, and cell death. Here we investigated, in human and rodent cell lines,
      whether TS induces cell death by apoptosis or by necrosis. As described for
      classic oxidants, TS induced apoptosis at low concentrations and necrosis at
      higher concentrations. We have previously described the induction of heat shock
      (HS) protein (HSP) (in particular, HSP70) in human monocytes exposed to TS. HSP70
      is implicated in the regulation of cell injury and cell death and, in particular,
      modulates apoptosis, as does the antiapoptotic oncoprotein Bcl-2. At both
      apoptotic and necrotic concentrations, TS induced a dose-dependent HSP70
      expression, whereas Bcl-2 was induced only at necrotic concentrations. TS- or HS
      induced HSP had no protective effects either on apoptosis or on necrosis, but
      HSP70 overexpression prevented TS-induced necrosis and consequently led to
      increased apoptosis. These results might reconcile the apparently contradictory
      data previously reported on the effects of HSP on apoptosis.

PMID- 9755111
TI  - Keratinocyte growth factor promotes alveolar epithelial cell DNA repair after
      H2O2 exposure.
AB  - Alveolar epithelial cell (AEC) injury and repair are important in the
      pathogenesis of oxidant-induced lung damage. Keratinocyte growth factor (KGF)
      prevents lung damage and mortality in animals exposed to various forms of oxidant
      stress, but the protective mechanisms are not yet established. Because DNA strand
      break (DNA-SB) formation is one of the earliest cellular changes that occurs
      after cells are exposed to an oxidant stress, we determined whether KGF reduces
      H2O2-induced pulmonary toxicity by attenuating AEC DNA damage. KGF (10-100 ng/ml)
      decreased H2O2 (0.05-0.5 mM)-induced DNA-SB formation in cultured A549 and rat
      alveolar type II cells measured by an alkaline unwinding, ethidium bromide
      fluorometric technique. The protective effects of KGF were independent of
      alterations in catalase, glutathione (GSH), or the expression of bcl-2 and bax,
      two protooncogenes known to regulate oxidant-induced apoptosis. Actinomycin D and
      cycloheximide abrogated protective effects of KGF. Furthermore, protection by KGF
      was completely blocked by 1) genistein, a tyrosine kinase inhibitor; 2)
      staurosporine and calphostin C, protein kinase C (PKC) inhibitors; and 3)
      aphidicolin, butylphenyl dGTP, and 2',3'-dideoxythymidine 5'-triphosphate,
      inhibitors of DNA polymerase. We conclude that KGF attenuates H2O2-induced DNA-SB
      formation in cultured AECs by mechanisms that involve tyrosine kinase, PKC, and
      DNA polymerases. These data suggest that the ability of KGF to protect against
      oxidant-induced lung injury is partly due to enhanced AEC DNA repair.

PMID- 9755112
TI  - Role of Ca2+/calmodulin-dependent phosphatase 2B in thrombin-induced endothelial
      cell contractile responses.
AB  - Thrombin-induced Ca2+ mobilization, activation of Ca2+/calmodulin-dependent
      myosin light chain (MLC) kinase (MLCK), and increased phosphorylation of MLCs
      precede and are critical to endothelial cell (EC) barrier dysfunction. Net MLC
      dephosphorylation after thrombin is nearly complete by 60 min and involves type 1
      phosphatase (PPase 1) activity. We now report that thrombin does not alter total
      PPase 1 activity in EC homogenates but rather decreases myosin-associated PPase 1
      activity. The PPase 1 inhibitor calyculin fails to prevent thrombin-induced MLC
      dephosphorylation. However, thrombin significantly increased the activity of Ca2+
      dependent PPase 2B in EC homogenates (approximately 1.5- to 2-fold), with PPase
      2B activation correlating with phosphorylation of the PPase 2B catalytic subunit.
      Western immunoblotting revealed PPase 2B to be present in cytoskeletal EC
      fractions, with specific PPase 2B inhibitors such as cyclosporin (200 nM) and
      deltamethrin (100 nM to 1 microM) attenuating thrombin-induced cytoskeletal
      protein dephosphorylation, including EC MLC dephosphorylation. These results
      suggest a model whereby thrombin-inducible contraction is determined by the
      phosphorylation status of EC MLC regulated by the balance between EC MLCK, PPase
      1 (constitutive), and PPase 2B (inducible) activities.

PMID- 9755113
TI  - Intravenous keratinocyte growth factor protects against experimental pulmonary
      injury.
AB  - Keratinocyte growth factor (KGF) administered by intratracheal instillation is
      well documented to stimulate the proliferation of alveolar and bronchial cells.
      In the present study, intravenous KGF was also shown to stimulate the
      proliferation of alveolar and bronchial cells in mice and rats, although to a
      lesser degree than intratracheal KGF. Despite the decreased potency of
      intravenous KGF on pulmonary cell 5-bromo-2'-deoxyuridine incorporation compared
      with intratracheal KGF, intravenous KGF was very effective in preventing
      experimental bleomycin-induced pulmonary dysfunction, weight loss, and mortality
      in either mice or rats and experimental hyperoxia-induced mortality in mice. The
      effectiveness of intravenous administration of KGF in preventing lung injury
      suggests that the mechanisms of the protective effect of KGF may involve more
      than pulmonary cell proliferation and also suggests the potential use of systemic
      KGF for clinical trials in settings of pulmonary injury.

PMID- 9755114
TI  - Immunotargeting of catalase to ACE or ICAM-1 protects perfused rat lungs against
      oxidative stress.
AB  - The pulmonary endothelium is susceptible to oxidative insults. Catalase
      conjugated with monoclonal antibodies (MAbs) against endothelial surface
      antigens, angiotensin-converting enzyme (MAb 9B9) or intercellular adhesion
      molecule-1 (MAb 1A29), accumulates in the lungs after systemic injection in rats
      (V. Muzykantov, E. Atochina, H. Ischiropoulos, S. Danilov, and A. Fisher. Proc.
      Natl. Acad. Sci. USA 93: 5213-5218, 1996). The present study characterizes the
      augmentation of antioxidant defense by these antibody-catalase conjugates in
      isolated rat lungs perfused for 1 h with catalase conjugated with either MAb 9B9,
      MAb 1A29, or control mouse IgG. Approximately 20% of the injected dose of Ab-125I
      catalase accumulated in the perfused rat lungs (vs. <5% for IgG-125I-catalase).
      After elimination of nonbound material, the lungs were perfused further for 1 h
      with 5 mM hydrogen peroxide (H2O2). H2O2 induced an elevation in tracheal and
      pulmonary arterial pressures (126 +/- 7 and 132 +/- 5%, respectively, of the
      control level), lung wet-to-dry weight ratio (7.1 +/- 0.4 vs. 6.0 +/- 0.01 in the
      control lungs), and ACE release into the perfusate (436 +/- 20 vs. 75 +/- 7 mU in
      the control perfusates). Both MAb 9B9-catalase and MAb 1A29-catalase
      significantly attenuated the H2O2-induced elevation in 1) angiotensin-converting
      enzyme release to the perfusate (215 +/- 14 and 217 +/- 38 mU, respectively), 2)
      lung wet-to-dry ratio (6.25 +/- 0.1 and 6.3 +/- 0.3, respectively), 3) tracheal
      pressure (94 +/- 4 and 101 +/- 4%, respectively, of the control level), and 4)
      pulmonary arterial pressure (103 +/- 3 and 104 +/- 7%, respectively, of the
      control level). Nonconjugated catalase, nonconjugated antibodies, nonspecific
      IgG, and IgG-catalase conjugate had no protective effect, thus confirming the
      specificity of the effect of MAb-catalase. These results support a strategy of
      catalase immunotargeting for protection against pulmonary oxidative injury.

PMID- 9755115
TI  - Temporal, spatial, and oxygen-regulated expression of hypoxia-inducible factor-1
      in the lung.
AB  - Hypoxia-inducible factor (HIF)-1 is a basic helix-loop-helix transcription factor
      that transactivates genes encoding proteins that participate in homeostatic
      responses to hypoxia. Several of these downstream gene products, such as
      erythropoietin, vascular endothelial growth factor, heme oxygenase-1, and
      inducible nitric oxide synthase, may contribute to the pathogenesis of pulmonary
      hypertension. Previous studies demonstrated increased HIF-1 mRNA levels in rats
      and mice subjected to hypoxia. In this study, we have demonstrated spatial,
      temporal, and O2-dependent expression of HIF-1 protein. Immunoblot analysis
      revealed hypoxic induction of HIF-1 in all cultured pulmonary cell types assayed,
      including those derived from pulmonary arterial endothelium and smooth muscle,
      bronchial epithelium, alveolar macrophages, alveolar epithelium, and
      microvascular endothelium. In contrast to all other cell types, pulmonary
      arterial smooth muscle cells expressed HIF-1 under nonhypoxic conditions.
      Immunohistochemistry and immunoblot analysis of ferret lungs demonstrated
      pulmonary expression of HIF-1 in vivo. HIF-1 protein expression was induced
      maximally when lungs were ventilated with 0 or 1% O2 for 4 h. On reoxygenation,
      HIF-1 was rapidly degraded, with a half-life of <1 min. These findings
      demonstrate that HIF-1 expression is tightly coupled to O2 concentration in vivo
      and are consistent with the involvement of HIF-1 in the physiological and
      pathophysiological responses to hypoxia in the lung.

PMID- 9755116
TI  - Regulation of ciliary beat frequency by both PKA and PKG in bovine airway
      epithelial cells.
AB  - Ciliary beating is required for the maintenance of lung mucociliary transport. We
      investigated the role of cyclic nucleotide-dependent protein kinases in
      stimulating ciliary beat frequency (CBF) in bovine bronchial epithelial cells
      (BBECs). cAMP-dependent protein kinase (PKA) activity and cGMP-dependent protein
      kinase (PKG) activity were distinguished after DEAE-Sephacel chromatography of
      BBEC extracts. cAMP levels and PKA activity are increased in BBECs stimulated
      with 0.01-1 mM isoproterenol, with a corresponding increase in CBF. cGMP levels
      and PKG activity are increased in BBECs stimulated with 0.1-10 microM sodium
      nitroprusside, with a corresponding increase in CBF. Direct protein kinase
      activating analogs of cAMP and cGMP (dibutyryl cAMP and 8-bromo-cGMP,
      respectively) also activate their specific kinases and stimulate CBF.
      Preincubation of BBECs with inhibitors of PKA or PKG [KT-5720 or Rp-8-(p
      chlorophenylthio)-guanosine 3',5'-cyclic monophosphothioate] results in the
      inhibition of specific kinase activity as well as in the inhibition of CBF. These
      studies suggest that the activation of either PKA or PKG can lead to the
      stimulation of CBF in bovine airway epithelium.

PMID- 9755117
TI  - Increased expression of heat shock protein-70 protects A549 cells against
      hyperoxia.
AB  - Acute and chronic lung injury secondary to hyperoxia remains an important
      complication in critically ill patients, and, consequently, there is interest in
      developing strategies to protect the lung against hyperoxia. Heat shock proteins
      (HSPs) confer protection against a broad array of cytotoxic agents. In this
      study, we tested the hypothesis that increased expression of the 70-kDa HSP
      (HSP70) would protect cultured human respiratory epithelium against hyperoxia.
      Recombinant A549 cells were generated in which human HSP70 was increased by
      stable transfection with a plasmid containing human HSP70 cDNA under control of
      the cytomegalovirus promoter (A549-HSP70 cells). A549-HSP70 cells exposed to
      hyperoxia had greater acute survival rates and clonogenic capacity compared with
      wild-type A549 cells and with control cells stably transfected with the empty
      expression plasmid. Hyperoxia-mediated lipid peroxidation and ATP depletion were
      also attenuated in A549-HSP70 cells exposed to hyperoxia. Increased expression of
      HSP70 did not detectably alter mRNA levels of the intracellular antioxidants
      manganese superoxide dismutase, catalase, and glutathione peroxidase.
      Collectively, these data demonstrate a specific in vitro protective role for
      HSP70 against hyperoxia and suggest that potential mechanisms of protection
      involve attenuation of hyperoxia-mediated lipid peroxidation and ATP depletion.

PMID- 9755118
TI  - Relevance of extracellular matrix, its receptors, and cell adhesion molecules in
      mammalian nephrogenesis.
AB  - Mammalian nephrogenesis begins by the reciprocal interaction of the ureteric bud
      with the undifferentiated mesenchyme. The mesenchyme differentiates into an
      epithelial phenotype with the development of the glomerulus and proximal and
      distal tubules. At the same time, the mesenchyme stimulates the branching
      morphogenesis of the ureteric bud that differentiates into the collecting ducts.
      These inductive interactions and differentiation events are modulated by a number
      of macromolecules, including the extracellular matrix (ECM), integrin receptors,
      and cell adhesion molecules. Many of these macromolecules exhibit spatiotemporal
      developmental regulation in the metanephros. Some are expressed in the
      mesenchyme, whereas others appear in the ureteric bud epithelia. The molecules
      expressed in the mesenchyme or at the epithelial:mesenchymal interface may serve
      as ligands while those in the epithelia serve as the receptors. In such a
      scenario the ligand and the receptor would be ideally suited for
      epithelial:mesenchymal paracrine/juxtacrine interactions that are also influenced
      by RGD sequences and Ca2+ binding domains of the ECM proteins and their
      receptors. This review addresses the role of such interactions in metanephric
      development.

PMID- 9755119
TI  - Hypertonicity activates MAP kinases and inhibits HCO-3 absorption via distinct
      pathways in thick ascending limb.
AB  - Mitogen-activated protein (MAP) kinases are activated by osmotic stress in a
      variety of cells, but their function and regulation in renal tubules is poorly
      understood. The present study was designed to examine the osmotic regulation of
      MAP kinases in the medullary thick ascending limb (MTAL) of the rat and to
      determine their possible role in the hyperosmotic inhibition of HCO-3 absorption
      in this segment. Tissues from the inner stripe of the outer medulla and
      microdissected MTALs were incubated at 37 degreesC in control (290 mosmol/kgH2O)
      or hyperosmotic (300 mM added mannitol) solution for 15 min. Activities of
      extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and
      p38 MAP kinase were then measured using immune complex assays. Hyperosmolality
      increased p38 MAP kinase activity (2.3-fold) and ERK activity (2.0-fold) but had
      no effect on JNK activity (1.1-fold). Exposure to hyperosmolality for various
      times showed that the activation of p38 MAP kinase was rapid (</=5 min) and was
      sustained for up to 60 min, whereas the activation of ERK was transient (ERK
      activity peaked at 15 min, then declined to basal levels at 30 min). Pretreatment
      with the MAP kinase kinase inhibitor PD98059 (15 microM) blocked the hyperosmotic
      activation of p38 MAP kinase and ERK but did not prevent hyperosmotic inhibition
      of HCO-3 absorption. These results show that hyperosmolality differentially
      activates p38 MAP kinase and ERK in the MTAL. In contrast, we found no evidence
      for involvement of JNK in the early response to hyperosmotic stress. Eliminating
      the activation of p38 MAP kinase and ERK does not prevent hyperosmotic inhibition
      of HCO-3 absorption, suggesting that hyperosmolality inhibits apical membrane
      Na+/H+ exchange (NHE3) activity via a signaling pathway distinct from these MAP
      kinase pathways.

PMID- 9755120
TI  - Activation of H+-ATPase by hypotonicity: a novel regulatory mechanism for H+
      secretion in IMCD cells.
AB  - The effect of hypotonicity on H+-ATPase activity was examined in cultured inner
      medullary collecting duct (mIMCD-3) cells. mIMCD-3 cells were grown to
      confluence, loaded with 2', 7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein
      (BCECF), and assayed for H+-ATPase activity measured as the Na+- and K+
      independent intracellular pH (pHi) recovery following an acid load. Exposure of
      mIMCD-3 cells to a hypotonic solution (150 mosmol/kgH2O) increased pHi recovery
      by approximately 350% (P < 0.0001). This effect was inhibited by
      diethylstilbestrol (an inhibitor of H+-ATPase) and was not dependent on external
      K+, indicating lack of involvement of H+-K+-ATPase. H+-ATPase activation was
      acute, independent of cell calcium, and was not secondary to Cl- channel
      activation. The magnitude of H+-ATPase upregulation was dependent on the
      osmolarity of the media, with maximum stimulation at 150 mosmol/kgH2O. H+-ATPase
      upregulation in hypotonicity was significantly blocked in the presence of
      staurosporine or calphostin C or in cells pretreated with phorbol 12-myristate 13
      acetate (PMA), indicating involvement of protein kinase C. Hypotonicity inhibited
      the Na+/H+ exchanger activity in mIMCD-3 cells, indicating that its stimulatory
      effect is specific to H+-ATPase. In conclusion, a novel regulatory mechanism of
      H+-ATPase by hypotonicity is described. The increased H+-ATPase activity in
      hypotonicity may be responsible for increased HCO-3 reabsorption and maintained
      acid-base homeostasis in hyposmolar states.

PMID- 9755121
TI  - Bradykinin may be involved in neuropeptide Y-induced diuresis, natriuresis, and
      calciuresis.
AB  - Neuropeptide Y (NPY) can cause diuresis, natriuresis, and calciuresis in rats
      independently of the pressure-natriuresis mechanism (A. Bischoff and M. C.
      Michel. Pflugers Arch. 435: 443-453, 1998). Because this is seen in systemic but
      not intrarenal NPY infusion, we have investigated the possible mediator of
      tubular NPY effects in anesthetized rats. In the present study, infusion of NPY
      (2 micrograms . kg-1 . min-1) enhanced renovascular resistance by approximately 8
      mmHg . ml-1 . min and enhanced urine and sodium excretion by approximately 450
      microliter/15 min and approximately 60-85 micromol/15 min, respectively. Acute
      renal denervation did not alter renovascular or tubular NPY effects, indicating
      that a neuronally released mediator is not involved. Treatment with the
      angiotensin II-receptor antagonist losartan prevented the decline of the
      renovascular response with time but did not modify tubular NPY effects. The
      bradykinin B2-receptor antagonist icatibant accelerated the decline of the
      renovascular NPY effects with time; concomitantly, it attenuated NPY-induced
      diuresis and natriuresis and abolished NPY-induced calciuresis. The converting
      enzyme inhibitor ramiprilat prevented the decline of the renovascular response
      with time; concomitantly, it magnified the NPY-induced diuresis, natriuresis, and
      calciuresis. We conclude that bradykinin may be involved in NPY-induced diuresis,
      natriuresis, and, in particular, calciuresis.

PMID- 9755122
TI  - Immunochemical characterization of Na+/H+ exchanger isoform NHE4.
AB  - Mammalian Na+/H+ exchangers (NHEs) are a family of transport proteins (NHE1
      NHE5). To date, the cellular and subcellular localization of NHE4 has not been
      characterized using immunochemical techniques. We purified a fusion protein
      containing a portion of rat NHE4 (amino acids 565-675) to use as immunogen. A
      monoclonal antibody (11H11) was selected by ELISA. It reacted specifically with
      both the fusion protein and to a 60- to 65-kDa polypeptide expressed in NHE4
      transfected LAP1 cells. By Western blot analysis, NHE4 was identified as a 65- to
      70-kDa protein that was expressed most abundantly in stomach and in multiple
      additional epithelial and nonepithelial rat tissues including skeletal muscle,
      heart, kidney, uterus, and liver. Subcellular localization of NHE4 in the kidney
      was evaluated by Western blot analysis of membrane fractions isolated by Percoll
      gradient centrifugation. NHE4 was found to cofractionate with the basolateral
      markers NHE1 and Na+-K+-ATPase rather than the luminal marker gamma-glutamyl
      transferase. In stomach, NHE4 was detected by immunoperoxidase labeling on the
      basolateral membrane of cells at the base of the gastric gland. We conclude that
      NHE4 is a 65- to 70-kDa protein with a broad tissue distribution. In two types of
      epithelial cells, kidney and stomach, NHE4 is localized to the basolateral
      membrane.

PMID- 9755123
TI  - Inducible transcriptional activity of bcn-1 element from laminin gamma1-chain
      gene promoter in renal and nonrenal cells.
AB  - Laminin is a major component of the extracellular matrix whose expression is
      regulated by growth factors. The laminin gamma1-chain promoter contains a newly
      identified transcriptional element denoted bcn-1 that is both active and
      inducible in mesangial cells. In this study, we explored activation of the bcn-1
      element in other renal and nonrenal cells. Treatment of rat glomerular epithelial
      cells (GEC) with phorbol 12-myristate 13-acetate (PMA) increased activity of the
      bcn-1 transcriptional element, within the context of the native laminin gamma1
      chain promoter or when cloned upstream of a heterologous promoter. Treatment of
      GEC with PMA induced nuclear DNA-binding activity, BCN-1, which was recognized by
      the bcn-1 motif in a gel shift assay. These results provide evidence that the bcn
      1 motif and its cognate BCN-1 factor(s) may regulate transcription of the laminin
      gamma1-chain in GEC. The bcn-1 element and its cognate BCN-1 DNA-binding activity
      were also inducible in monkey kidney COS-7 and in human T cell Jurkat lines. SDS
      PAGE of in situ ultraviolet cross-linked nucleoproteins from GEC, COS, and Jurkat
      cells revealed one major 110-115 kDa adduct in all three cell lines. These
      results demonstrate that the bcn-1 element is active in renal and nonrenal cells
      from different mammalian species where the same protein contributes to the
      inducible BCN-1 DNA-binding activity.

PMID- 9755124
TI  - Differential expression, abundance, and regulation of Na+-phosphate cotransporter
      genes in murine kidney.
AB  - Three classes of high-affinity Na+-Pi cotransporters are expressed in mammalian
      kidney. These include Npt1 (type I), Npt2 (type II), and the cellular receptors
      for gibbon ape leukemia virus (Glvr-1) and amphotropic murine retrovirus (Ram-1)
      (type III). We defined the tissue distribution as well as the relative renal
      abundance of Npt1, Npt2, Glvr-1, and Ram-1 mRNAs and examined the effects of low
      Pi diet, the Hyp mutation, and growth hormone (GH) on their renal expression by
      ribonuclease protection assay. In normal mouse kidney, Npt1, Npt2, Glvr-1, and
      Ram-1 accounted for 15 +/- 1.0, 84 +/- 1.0, 0.5 +/- 0.2, and 0.5 +/- 0.3% of
      total Na+-Pi cotransporter mRNAs, respectively. Evidence was obtained for low
      abundance Npt1 mRNA expression in liver and Npt2 mRNA expression in intestine,
      whereas Glvr-1 and Ram-1 mRNAs were also detected in bone, intestine, heart, and
      liver. Npt2 mRNA was localized to proximal tubules in the renal outer cortex,
      whereas Glvr-1 transcripts were detected throughout the kidney by in situ
      hybridization. The Hyp mutation elicited a significant reduction in renal Npt1
      and Npt2 mRNAs (78 +/- 8 and 57 +/- 3% of normal, respectively), whereas neither
      low-Pi diet nor GH influenced the renal abundance of Npt1 and Npt2 transcripts.
      Renal Glvr-1 mRNA expression was significantly increased in Hyp mice and GH
      treated mice (145 +/- 6 and 165 +/- 5% of control, respectively), whereas the
      renal abundance of Ram-1 transcript was unaffected by either the Hyp mutation,
      low-Pi diet, or GH treatment. In summary, we demonstrate that Npt2 is the
      predominant Na+-Pi cotransporter in mouse kidney, that Npt2 and Glvr-1 have
      distinct patterns of renal expression, and that the Hyp mutation modulates the
      renal expression of Npt1, Npt2, and Glvr-1 mRNAs. Our results suggest that
      increased renal Glvr-1 mRNA may contribute to GH stimulation of renal Na+-Pi
      cotransport.

PMID- 9755125
TI  - Characterization of angiotensin IV-degrading enzymes and receptors on rat
      mesangial cells.
AB  - Because mesangial cells (MC) are a target and a degradation site for angiotensin
      II (ANG II), we characterized the degrading enzymes and receptors of ANG IV, a
      metabolite of ANG II, on these cells. ANG IV was metabolized into its NH2
      terminal deleted peptides, ANG II-(4-8), ANG II-(5-8), and ANG II-(6-8) by rat
      MC. Total protection of ANG IV was obtained only when PC-18, a specific
      aminopeptidase N (APN) inhibitor, and JFH-27A, a mixed inhibitor of
      dipeptidylaminopeptidase (DAP) and neutral endopeptidase (NEP), were
      simultaneously added. In contrast, thiorphan, an NEP inhibitor, was inactive.
      These results demonstrate the exclusive role of APN and DAP in ANG IV
      degradation. 125I-labeled ANG IV binding was studied in the presence of PC-18 and
      JFH-27A to suppress ligand degradation. Under these conditions, ANG IV-specific
      receptors could be demonstrated with a KD of 1.8 nM and a density of 55 fmol/mg.
      In contrast with MC, no evidence for ANG IV receptors could be obtained in
      freshly isolated glomeruli. ANG IV stimulated cytosolic calcium concentration in
      MC, whereas its NH2-terminal deleted metabolites were inactive. Therefore, ANG IV
      must be protected from degradation by APN and DAP in studies on the nonimmediate
      biological effects of this peptide.

PMID- 9755126
TI  - Dietary K+ restriction upregulates total and Sch-28080-sensitive bicarbonate
      absorption in rat tIMCD.
AB  - In tubules from the terminal segment of the inner medullary collecting duct
      (tIMCD) from rats with chronic metabolic acidosis, our laboratory has shown that
      bicarbonate absorption (JtCO2) is inhibited by removal of K+ from the luminal
      fluid or by the addition of Sch-28080 to the perfusate. The present study asked
      whether total and/or Sch-28080-sensitive JtCO2 is regulated by changes in
      systemic K+ homeostasis. Rat tIMCD tubules were perfused in vitro in symmetrical,
      HCO-3/CO2-buffered solutions containing 10 mM KCl + 6 mM NH4Cl. Total and Sch
      28080-sensitive JtCO2 were measured in rats with varying K+ intake. In K+-replete
      rats, baseline JtCO2 was 2.1 +/- 0.3 pmol . mm-1 . min-1 (n = 6). In rats fed a
      K+-deficient diet for 3 days, JtCO2 was 5.4 +/- 0.7 pmol . mm-1 . min-1 (n = 16,
      P < 0. 05). To determine the mechanism for the increase in HCO-3 absorption
      observed with K+ restriction, the Sch-28080-sensitive component of JtCO2 was
      measured in each treatment group. Following the addition of Sch-28080 (10 microM)
      to the perfusate, a 40% reduction in JtCO2 was observed in K+-restricted rats.
      JtCO2 was not reduced following the addition of Sch-28080 in rats with normal K+
      intake. Because Sch-28080-sensitive JtCO2 was increased in K+-restricted rats,
      Sch-28080-sensitive JtCO2 was studied further in tIMCD tubules from rats in this
      treatment group. In K+-restricted rats, JtCO2 decreased by 20% following the
      addition of 5 mM ouabain to the perfusate. This ouabain-induced decline in JtCO2
      was observed both in the presence and in the absence of Sch-28080. We conclude
      that total and Sch-28080-sensitive net acid secretion is increased with dietary
      K+ restriction. However, since approximately 50% of JtCO2 is insensitive to both
      Sch-28080 and ouabain, future studies will be necessary to define other
      mechanisms of luminal acidification in the rat tIMCD.

PMID- 9755127
TI  - Cloning, characterization, and gene organization of K-Cl cotransporter from pig
      and human kidney and C. elegans.
AB  - We isolated and characterized the cDNAs for the human, pig, and Caenorhabditis
      elegans K-Cl cotransporters. The pig and human homologs are 94% identical and
      contain 1,085 and 1,086 amino acids, respectively. The deduced protein of the C.
      elegans K-Cl cotransporter clone (CE-KCC1) contains 1,003 amino acids. The
      mammalian K-Cl cotransporters share approximately 45% similarity with CE-KCC1.
      Hydropathy analyses of the three clones indicate typical KCC topology patterns
      with 12 transmembrane segments, large extracellular loops between transmembrane
      domains 5 and 6 (unique to KCC), and large COOH-terminal domains. Human KCC1 is
      widely expressed among various tissues. This KCC1 gene spans 23 kb and is
      organized in 24 exons, whereas the CE-KCC1 gene spans 3.5 kb and contains 10
      exons. Transiently and stably transfected human embryonic kidney cells (HEK-293)
      expressing the human, pig, and C. elegans K-Cl cotransporter fulfilled two (pig)
      or five (human and C. elegans) criteria for increased expression of the K-Cl
      cotransporter. The criteria employed were basal K-Cl cotransport; stimulation of
      cotransport by swelling, N-ethylmaleimide, staurosporine, and reduced cell Mg
      concentration; and secondary stimulation of Na-K-Cl cotransport.

PMID- 9755128
TI  - Redistribution of Na+/H+ exchanger isoform NHE3 in proximal tubules induced by
      acute and chronic hypertension.
AB  - Redistribution of apical Na+/H+ exchangers (NHE) in the proximal tubules as a
      plausible mechanism of pressure natriuresis was investigated with confocal
      immunofluorescence microscopy in Sprague-Dawley rats (SD), spontaneously
      hypertensive rats (SHR), and two-kidney, one-clip Goldblatt hypertensive rats
      (GH). NHE isoform NHE3 was localized in the brush border of proximal tubules in
      SD. Twenty minutes of induced acute hypertension (20-40 mmHg) resulted in a
      pronounced redistribution of isoform NHE3 from the brush border into the base of
      microvilli, where clathrin-coated pits were localized. Prehypertensive young SHR
      (5 wk old, mean blood pressure 105 +/- 3 mmHg, n = 11) produced similar findings.
      However, NHE3 was found to concentrate in the base of microvilli in adult SHR (12
      wk old, mean blood pressure 134 +/- 6 mmHg, n = 12) and nonclipped kidneys of GH
      (mean blood pressure 131 +/- 6 mmHg, n = 6). In clipped kidneys of GH, which were
      not exposed to the hypertension because of the arterial clips, NHE3 was localized
      on the brush border as in normal SD. No further redistribution of NHE3 was
      detected in adult SHR or GH when acute hypertension was induced. Since both acute
      and chronic increase of arterial pressure can provoke the redistribution of
      apical NHE in proximal tubules, the pressure-induced NHE redistribution could be
      a physiological response and an integral part of pressure natriuresis.

PMID- 9755129
TI  - Effects of antihypertensive drugs on autoregulation of RBF and glomerular
      capillary pressure in SHR.
AB  - The relationship between systemic blood pressure and glomerular capillary
      pressure (Pgc) in spontaneously hypertensive rats (SHR) during treatment with
      antihypertensive drugs is still unclear. The effects of an angiotensin-converting
      enzyme inhibitor (enalapril), two calcium channel antagonists (nifedipine and
      verapamil), and an alpha1-receptor blocker (doxazosin) on renal blood flow (RBF)
      autoregulation, Pgc, and renal segmental resistances were therefore studied in
      SHR. Recordings of RBF autoregulation were done before and 30 min after
      intravenous infusion of the different drugs, and Pgc was thereafter measured with
      the stop-flow technique. When the mean arterial pressure (MAP) was reduced to
      approximately 120 mmHg by infusions of doxazosin or enalapril, the lower pressure
      limit of RBF autoregulation was reduced significantly. Nifedipine or verapamil
      abolished RBF autoregulation. Doxazosin did not change Pgc (43.6 +/- 1.4 vs. 46.7
      +/- 1.5 mmHg in controls, P > 0.5), enalapril lowered (41.3 +/- 0.8 mmHg, P <
      0.01), and the calcium channel antagonists increased Pgc [53.7 +/- 1.4 mmHg
      (nifedipine) and 54.8 +/- 1.2 mmHg (verapamil), P < 0.01]. When MAP was reduced
      to approximately 85 mmHg by drugs, Pgc was reduced to 43.3 +/- 1.7 mmHg after
      nifedipine (P > 0.2 vs. control), whereas Pgc after enalapril was 38.5 +/- 0.5
      mmHg (P < 0.05 vs. control). Enalapril reduced Pgc mainly by reducing efferent
      resistance. During treatment with calcium channel antagonists, Pgc became
      strictly dependent on MAP. Monotherapy with nifedipine may increase Pgc and by
      this mechanism accelerate glomerulosclerosis if a strict blood pressure control
      is not obtained.

PMID- 9755130
TI  - Inactivation of kinase cascades in mesangial cells grown on collagen type I.
AB  - Growth on collagen type I gels is known to suppress the mitogenic responsiveness
      of mesangial cells. Because these cells proliferate in some renal diseases and
      themselves synthesize collagen type I, we examined the influence of growth on
      collagen upon several kinase signaling cascades involved in mesangial cell
      proliferation. Quiescent mesangial cells grown on collagen type I and then
      stimulated with serum showed a markedly diminished induction of the protooncogene
      c-fos, compared with their counterparts on plastic or fibronectin. This effect
      was accompanied by decreased activation of mitogen-activated (Erk family) and
      Ca2+/calmodulin-dependent protein kinases. Cells on collagen showed lower basal
      protein kinase C (PKC) activity and diminished levels of PKC-alpha and -zeta
      isoforms. Global phosphorylation of tyrosine residues was diminished on collagen,
      and tyrosine phosphorylation of Erk and focal adhesion kinase in response to
      serum was not detected, in contrast to cells on plastic. We conclude that
      attachment of mesangial cells to collagen type I results in a broad suppression
      of protein phosphorylation that is reflected in diminished induction of the c-fos
      gene and probably underlies the conversion of cultured mesangial cells to a
      nonproliferative phenotype.

PMID- 9755131
TI  - Cyclosporin A increases hypoxia and free radical production in rat kidneys:
      prevention by dietary glycine.
AB  - The major side effect of cyclosporin A is severe nephrotoxicity. It is likely
      that cyclosporin A causes vasoconstriction leading to hypoxia-reperfusion injury;
      therefore, these experiments were designed to attempt to obtain physical evidence
      for hypoxia and free radical production in kidney following cyclosporin A. Rats
      were treated daily with cyclosporin A (25 mg/kg ig) for 5 days, and pimonidazole,
      a hypoxia marker, was injected 2 h after the last dose of cyclosporin A. A dose
      of alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN) was injected 3 h after
      cyclosporin A to trap free radicals. Cyclosporin A doubled serum creatinine and
      decreased glomerular filtration rates by 65% as expected. Pimonidazole adduct
      binding in the kidney was increased nearly threefold by cyclosporin A, providing
      physical evidence for tissue hypoxia. Moreover, cyclosporin A increased 4
      POBN/radical adducts nearly sixfold in the urine but did not alter levels in the
      serum. Glycine, which causes vasodilatation and prevents cyclosporin A toxicity,
      minimized hypoxia and blocked free radical production; however, it did not alter
      cyclosporin A blood levels. These results demonstrate for the first time that
      cyclosporin A causes hypoxia and increases production of a new free radical
      species exclusively in the kidney. Therefore, it is concluded that cyclosporin A
      causes renal injury by mechanisms involving hypoxia-reoxygenation, effects which
      can be prevented effectively by dietary glycine.

PMID- 9755132
TI  - Cyclooxygenase-2 participates in tubular flow-dependent afferent arteriolar tone:
      interaction with neuronal NOS.
AB  - To delineate the microvascular role of cyclooxygenase-2 (Cox-2) in modulating
      tubuloglomerular feedback (TGF) signals and to determine its relationship to
      neuronal nitric oxide synthase (nNOS), afferent (AA) and efferent (EA) arteriolar
      diameters of rat kidneys were assessed using the blood-perfused juxtamedullary
      nephron technique. The Cox-2 inhibitor NS-398 (10 microM) did not alter AA
      diameters in untreated kidneys but significantly constricted AAs by 17.0 +/- 2.2%
      in kidneys treated with 10 mM acetazolamide, which enhances TGF-mediated AA
      constriction by increasing distal volume delivery. The NS-398-induced AA
      constriction was prevented after interruption of distal delivery by transection
      of the loops of Henle. The effect was selective for AAs since NS-398 did not
      influence EAs of untreated or acetazolamide-treated kidneys. Pretreatment with
      the nNOS inhibitor S-methyl-L-thiocitrulline (10 microM) prevented the NS-398
      induced AA constriction observed during acetazolamide treatment. Although we
      previously demonstrated that acetazolamide treatment enhanced AA constrictor
      response to S-methyl-L-thiocitrulline, the enhancement by acetazolamide was
      inhibited by pretreatment with 10 microM NS-398 (16.4 +/- 1.9 and 15. 0 +/- 0.5%
      with and without acetazolamide, respectively, P > 0.05). These results indicate
      that, during increased activation of TGF-dependent vasoconstrictor signals, Cox-2
      generates vasodilatory metabolites in response to increased nNOS activity and
      thus participates in the counteracting modulation of TGF-mediated AA
      constriction.

PMID- 9755133
TI  - Selective increase of cyclooxygenase-2 expression in a model of renal ablation.
AB  - Previous studies have suggested a possible role for prostaglandins (PGs) in
      mediating alterations in nephron structure and function ensuing after renal
      ablation. Two isoforms of cyclooxygenase (COX) have been described: constitutive
      (COX-1) and inducible (COX-2). We examined expression of these isoforms following
      subtotal renal ablation (5/6 ablation, RA) in rats. In renal cortex, COX-2 mRNA
      and immunoreactive protein (IP) increased progressively compared with sham
      operated littermates. In contrast, there were no significant changes in COX-1
      mRNA expression. In normal kidney, cortical COX-1 IP was immunolocalized
      predominantly to mesangial cells and collecting tubules, whereas COX-2 IP was
      found in a subset of cortical thick ascending limb of Henle's loop (CTAL) cells
      in the region of the macula densa (MD). Following RA, significantly increased COX
      2 IP was detected in the MD and surrounding CTAL cells. In addition, fainter
      immunoreactive COX-2 was detected in scattered visceral epithelial cells and
      mesangial cells of the glomerulus. Immunoblotting of isolated glomeruli
      demonstrated a selective increase of glomerular immunoreactive COX-2 expression
      following RA. No change of COX-1 expression was seen. To determine COX activity,
      isolated glomeruli were incubated with arachidonic acid and PGE2 measured by
      enzyme immunoassay (EIA). Compared with sham, glomeruli from 2 wk RA produced
      significantly more PGs. SC-58560, a selective COX-1 inhibitor, did not inhibit PG
      production in the remnant glomeruli at concentrations up to 10(-4) M, whereas SC
      58236, a relatively selective COX-2 inhibitor, significantly inhibited PG
      production by RA glomeruli. In preliminary studies, to define mechanisms of
      altered expression of glomerular COX-2, rat mesangial cells were incubated with
      serum from sham or 2 wk RA. There were significant increases in COX-2 expression
      in response to 2 wk RA serum. In summary, these results indicate selective
      increases in renal cortical COX-2 expression following renal ablation.

PMID- 9755134
TI  - Size characteristics of larger academic human environmental health programs in
      the United States.
AB  - We have performed a benchmark exercise evaluating larger academic programs in
      human environmental health sciences. These programs are located at schools of
      public health and at other institutions that have NIEHS Centers of Excellence.
      The largest programs were those in which there was both an NIEHS center and a
      public health graduate education program. This suggests that there is synergy
      between environmental health sciences research and involvement in public and
      community health.

PMID- 9755135
TI  - Update on national toxicology program (NTP) assays with genetically altered or
      "transgenic" mice.
AB  - The NTP is evaluating several lines of genetically altered mice for possible use
      in identifying and assessing carcinogens. The NIEHS/NTP programs and progress in
      this area were recently reviewed by the NTP Board of Scientific Counselors (BSC).
      A number of comments and concerns were raised. This commentary summarizes and
      responds to the BSC review and offers some thoughts on future directions for this
      line of research as well as possible ways genetically altered mice might be
      integrated into a comprehensive testing strategy.

PMID- 9755136
TI  - Human exposure assessment and the National Toxicology Program.
AB  - The National Institute of Environmental Health Sciences/National Toxicology
      Program (NIEHS/NTP) is developing a new interagency initiative in exposure
      assessment. This initiative involves the NIEHS, the Centers for Disease Control
      and Prevention through its National Center for Environmental Health, the National
      Institute for Occupational Safety and Health, the EPA, and other participating
      institutes and agencies of the NTP. This initiative will benefit public health
      and priority setting in a number of ways. First, as discussed above, it will
      strengthen the scientific foundation for risk assessments by the development of
      more credible exposure/response relationships in people by improving cross
      species extrapolation, the development of biologically based dose-response
      models, and the identification of sensitive subpopulations and for "margin of
      exposure" based estimates of risk. Second, it will provide the kind of
      information necessary for deciding which chemicals should be studied with the
      limited resources available for toxicological testing. For example, there are
      85,000 chemicals in commerce today, and the NTP can only provide toxicological
      evaluations on 10-20 per year. Third, we would use the information obtained from
      the exposure initiative to focus our research on mixtures that are actually
      present in people's bodies. Fourth, we would obtain information on the kinds and
      amount of chemicals in children and other potentially sensitive subpopulations.
      Determinations of whether additional safety factors need to be applied to
      children must rest, in part, upon comparative exposure analyses between children
      and adults. Fifth, this initiative, taken together with the environmental genome
      initiative, will provide the science base essential for meaningful studies on
      gene/environment interactions, particularly for strengthening the evaluation of
      epidemiology studies. Sixth, efficacy of public health policies aimed at reducing
      human exposure to chemical agents could be evaluated in a more meaningful way if
      body burden data were available over time, including remediation around Superfund
      sites and efforts to achieve environmental justice. The exposure assessment
      initiative is needed to address public health needs. It is feasible because of
      recent advances in analytical technology and molecular biology, and it is an
      example of how different agencies can work together to better fulfill their
      respective missions.

PMID- 9755137
TI  - New findings on sources and biokinetics of lead in human breast milk: bone lead
      can target both nursing infant and fetus.

PMID- 9755138
TI  - Cytochromes P450 and species differences in xenobiotic metabolism and activation
      of carcinogen.
AB  - The importance of cytochrome P450 isoforms to species differences in the
      metabolism of foreign compounds and activation of procarcinogens has been
      identified. The possible range of P450 isozymes in significant variations in
      toxicity exhibited by experimental rodent species may have a relevance to
      chemical risk assessment, especially as human P450s are likely to show changes in
      the way they metabolize xenobiotics. Consequently, in the safety evaluation of
      chemicals, we should be cautious in extrapolating results from experimental
      animal models to humans. This paper focuses on examples in which species
      differences in P450s lead to significant alterations in carcinogenic response,
      and includes a discussion of the current procedures for toxicity screening, with
      an emphasis on short-term tests.

PMID- 9755139
TI  - Effect of NOx on the somatic chromosomes of goldsmiths.
AB  - The genotoxic effect of NOx was investigated on somatic human chromosomes
      obtained from lymphocytes of 45 goldsmiths exposed to 1770.5 mg/m3 NOx in ambient
      air at normal temperature and pressure and compared to an equal number of matched
      controls breathing air containing 50 microgram/m3 NOx. Short-term lymphocyte
      cultures were set up from blood collected from both exposed and control
      individuals by venipuncture in heparinized sterile syringes. Mitotic index (MI),
      chromosome aberrations (CAs), sister chromatid exchanges (SCEs), and satellite
      associations (SAs) were analyzed. All the parameters showed a significant
      increase (p<0.01 and p<0.05) in the exposed individuals as compared to the
      controls: MI (9.57 vs. 5.01), CAs (3. 48 vs. 0.711), SCEs (10.56 vs. 7.02), and
      SAs (25.97 vs. 12.84), respectively. Occurrence of DG-type SAs (one D-group
      chromosome and one G-group chromosome) was highest and 3 D-type (three D-group
      chromosomes) lowest. NOx was thus found to be genotoxic for humans.

PMID- 9755140
TI  - Carbon monoxide and hospital admissions for congestive heart failure: evidence of
      an increased effect at low temperatures.
AB  - The combined effects of carbon monoxide and low temperature on daily variation in
      hospital admissions for congestive heart failure (CHF) were examined for a 4-year
      period in Chicago, Illinois. Medicare hospital admissions for CHF were analyzed
      as a function of the maximum hourly temperature, maximum hourly levels of carbon
      monoxide (CO), and other criteria pollutants in Chicago for each day of the 4
      year period (1986-1989). The regression analyses for the time series were
      conducted using single and multipollutant models with interaction terms and
      adjustments for weather, weekly cycles, seasonal effects, and secular trend. The
      data were also grouped into three temperature ranges, <40 degrees, 40 degrees-75
      degrees, and >75 degrees F, and the relationship between CO and CHF admissions
      was evaluated for each range. For the 4-year time series, the CO level was
      positively associated with hospital admissions for CHF in the single pollutant
      and multipollutant models after adjustment for seasonal effects and weather
      pattern. The relative risks of hospital admissions for CHF in Chicago associated
      with the 75th percentile of exposure to CO in the high, medium, and low
      temperature ranges were 1.02 [95% confidence interval (CI), 0.95-1.10], 1.09 (CI,
      1.04-1.14), and 1.15 (CI, 1.09-1.22), respectively. In these data, the effect of
      CO on hospital admissions for CHF was temperature dependent, with the magnitude
      of the effect increasing with decreasing temperature. This synergy may help to
      explain the association between ambient CO and CHF admissions demonstrated in
      other studies.

PMID- 9755142
TI  - Variability of house dust mite allergen exposure in dwellings.
AB  - The variability of repeated house dust mite (HDM) allergen determinations at the
      same site within 3-24 months was evaluated on previously collected samples.
      Between two and four repeated measurements of Der p 1, a major allergen of
      Dermatophagoides pteronyssinus and Der f 1, a major allergen of D. farinae, on 46
      carpets and 31 mattresses were analyzed. In 90% of carpets and mattresses, HDM
      allergen concentrations were clinically relevant (at least one measurement >0.1
      microg Der p 1 + Der f 1/g dust). The coefficients of variation (CVs) for
      allergen concentrations in repeated samples over time (55.3-82.0% for the two
      allergens in beds and carpets) were clearly greater than the CVs for multiple
      samples collected at the same time (4.0-32.6%). Determination of allergen mass
      per square meter of surface instead of concentration per gram of dust resulted in
      an even greater CV (72.3-86.7%). The 95% range of expected values was about 10
      fold above and below the result of a single determination. We conclude that
      single determinations of HDM allergen in dust give very limited information about
      long-term exposure of an individual to the allergen. Repeated measurements are
      recommended. Studies of factors that affect HDM allergen exposure must be planned
      with appropriate sample sizes.

PMID- 9755141
TI  - Prevalence of elevated blood lead levels in an inner-city pediatric clinic
      population.
AB  - In November 1997, the Centers for Disease Control and Prevention (CDC) released
      revised guidelines for lead poisoning screening, including a recommendation that
      states and regions individualize screening policies based on local prevalence of
      elevated lead levels. The purpose of this study was to collect prevalence data
      for a Philadelphia, Pennsylvania, inner-city pediatric outpatient population
      previously not known to have elevated blood lead levels in order to determine its
      risk for lead exposure and screening requirements. Charts were reviewed for 817
      children of 10 months through 6 years of age whose venous blood lead levels were
      obtained as part of their routine health care over a 12-month period ending
      October 1992. None of these children had a history of previously elevated lead
      levels. Prevalence of elevated lead levels was determined for this population and
      correlated with patient age, sex, race, and insurance type. More than two-thirds
      (68%) of the study patients had a blood lead level of [Greater than and equal
      to]10 microg/dl. Elevated blood lead levels were associated with black race
      (p<0.0001), but not with sex or insurance type. The percentage of children with
      elevated blood lead levels was highest at ages 37-48 months. A majority of the
      children screened had lead levels in excess of the CDC threshold for an abnormal
      lead level (10 microgram/dl). This is the highest reported prevalence within a
      U.S. pediatric clinic population. In view of this extremely high prevalence,
      clinicians and public health personnel caring for children in Philadelphia inner
      city clinics must follow the intent of the new CDC guidelines by increasing their
      efforts in the areas of screening, follow-up, and environmental interventions. To
      ensure a lead-safe upbringing for children in the United States, state health
      officials nationwide should perform local risk assessments before considering
      policy transitions from universal to targeted screening.

PMID- 9755143
TI  - Antibodies to toluene diisocyanate in an environmentally exposed population.
AB  - Residents living near a polyurethane foam manufacturing facility expressed
      concern to health officials over chemical emissions from the plant. Environmental
      monitoring of ambient air near the plant indicated the presence of toluene
      diisocyanate (TDI), which was used in foam production. Health officials collected
      blood samples from 113 residents and analyzed the blood sera for antibodies to
      TDI and related diisocyanates. Ten of the 113 residents (9%) had elevated levels
      of IgG or IgE antibodies specific for one or more diisocyanates. Exposure
      histories were taken from antibody-positive individuals to identify possible
      occupational exposure to TDI or the use of diisocyanate-containing consumer
      products. Exposure to TDI in ambient air may be responsible for the positive
      antibody responses detected in some residents of the community.

PMID- 9755144
TI  - Relationships of lead in breast milk to lead in blood, urine, and diet of the
      infant and mother.
AB  - We have obtained stable lead isotope and lead concentration data from a
      longitudinal study of mobilization of lead from the maternal skeleton during
      pregnancy and lactation and in which the newly born infants were monitored for 6
      months postpartum to evaluate the effects of the local environment on lead body
      burden of the infant. Samples of maternal and infant blood, urine, and diet and
      especially breast milk were measured for 21 mothers and 24 infants. Blood lead
      concentrations were less than 5 microg/dl in all except one subject. The mean
      lead concentration in breast milk +/- standard deviation was 0.73 +/- 0.70
      microg/kg. In seven subjects for whom serial breast milk sampling was possible,
      the lead concentration varied by factors of from 2 to 4, and for three subjects
      there was an increase at or after 90 days postpartum. For the first 60-90 days
      postpartum, the contribution from breast milk to blood lead in the infants varied
      from 36 to 80%. Multiple linear regression analyses indicated statistically
      significant relationships for some of the variables of isotope ratios and lead
      concentrations between breast milk, blood, urine, and diet for infants and
      mothers. For example, the analyses revealed that both a mother's breast milk
      207Pb/206Pb and 206Pb/204Pb ratios and lead concentration provide information to
      predict her infant's blood 207Pb/206Pb and 206Pb/204Pb ratios. The major sources
      of lead in breast milk are from the maternal bone and diet. An evaluation of
      breast milk lead concentrations published over the last 15 years indicates that
      studies in which the ratio of lead concentrations in breast milk to lead
      concentrations in whole maternal blood (Multiple>100) were greater than 15 should
      be viewed with caution because of potential contamination during sampling and/or
      laboratory analyses. Selected studies also appear to show a linear relationship
      between breast milk and maternal whole blood, with the percentage of lead in
      breast milk compared with whole blood of <3% in subjects with blood lead levels
      ranging from 2 to 34 microgram/dl. The levels of lead in breast milk are thus
      similar to those in plasma. Breast-fed infants are only at risk if the mother is
      exposed to high concentrations of contaminants either from endogenous sources
      such as the skeleton or exogenous sources.

PMID- 9755145
TI  - Chlorinated hydrocarbons in women with repeated miscarriages.
AB  - This study was conducted to investigate a possible etiological role of
      chlorinated hydrocarbons in the pathogenesis of repeated miscarriages. The blood
      levels of chlorinated hydrocarbons [CHCs: pentachlorophenol,
      hexachlorocyclohexane, hexachlorobenzene, the dichlorodiphenyltrichloroethane
      (DDT) group, polychlorinated biphenyls] were determined in 89 women with repeated
      miscarriages, who were referred to the University Hospital of Obstetrics and
      Gynecology of Heidelberg for investigations between 1989 and 1993, and compared
      to a previously investigated reference population. In more than 20% of the women,
      at least one of the CHC levels exceeded the reference range. CHC levels did not
      differ significantly between women with primary or secondary and early or late
      miscarriages; neither did they differ between women with hormonal or
      immunological disorders as causes of repeated miscarriages or women with
      idiopathic repeated miscarriages. No significant associations were detected
      between CHC levels and further conceptions or the outcome of further pregnancies.
      As significant associations were found between increasing CHC blood
      concentrations and immunological and hormonal changes, CHCs may have an impact on
      the pregnancy course in certain cases.

PMID- 9755146
TI  - Public health policy and the National Toxicology Program.

PMID- 9755147
TI  - Re: the use of offspring sex ratios in the search for endocrine disruptors.

PMID- 9755148
TI  - New NTP centers meet the need to know.

PMID- 9755149
TI  - 20 years of toxicology.
AB  - With over 80,000 chemicals being used in commerce worldwide, it is important to
      identify the human health effects of these chemicals and the levels of exposure
      at which they are harmful to humans. In order to address this need, the National
      Toxicology Program (NTP) was established in 1978; since then, the NTP has become
      the world's leader in designing, conducting, and interpreting various types of
      toxicity assays.

PMID- 9755150
TI  - New tricks for an old assay.
AB  - For decades, a number of guinea pig tests have been used to identify human
      contact allergens in workplace and consumer products, but these tests have
      limitations. In addition to using large numbers of test animals, they also
      provide only subjective measurements, because the allergic activity is measured
      by watching the skin for redness. Furthermore, coloring in some chemicals that
      are evaluated may mask reddening of the skin, thus obscuring the results. Since
      the 1980s, investigators have sought alternative test methods that would reduce
      the number of animals required and address the limitations of current tests.

PMID- 9755151
TI  - Trinucleotide expansion diseases in the context of micro- and minisatellite
      evolution, Hammersmith Hospital, April 1-3, 1998.

PMID- 9755152
TI  - DNA damage checkpoint in budding yeast.
AB  - Eukaryotic cells have evolved a network of control mechanisms, known as
      checkpoints, which coordinate cell-cycle progression in response to internal and
      external cues. The yeast Saccharomyces cerevisiae has been invaluable in
      dissecting genetically the DNA damage checkpoint pathway. Recent results on
      posttranslational modifications and protein-protein interactions of some key
      factors provide new insights into the architecture of checkpoint protein
      complexes and their order of function.

PMID- 9755153
TI  - Potassium channel openers require ATP to bind to and act through sulfonylurea
      receptors.
AB  - KATP channels are composed of a small inwardly rectifying K+ channel subunit,
      either KIR6.1 or KIR6.2, plus a sulfonylurea receptor, SUR1 or SUR2 (A or B),
      which belong to the ATP-binding cassette superfamily. SUR1/KIR6.2 reconstitute
      the neuronal/pancreatic beta-cell channel, whereas SUR2A/KIR6.2 and SUR2B/KIR6.1
      (or KIR6.2) are proposed to reconstitute the cardiac and the vascular-smooth
      muscle-type KATP channels, respectively. We report that potassium channel openers
      (KCOs) bind to and act through SURs and that binding to SUR1, SUR2A and SUR2B
      requires ATP. Non-hydrolysable ATP-analogues do not support binding, and Mg2+ or
      Mn2+ are required. Point mutations in the Walker A motifs or linker regions of
      both nucleotide-binding folds (NBFs) abolish or weaken [3H]P1075 binding to
      SUR2B, rendering reconstituted SUR2B/KIR6.2 channels insensitive towards KCOs.
      The C-terminus of SUR affects KCO affinity with SUR2B approximately SUR1 > SUR2A.
      KCOs belonging to different structural classes inhibited specific [3H]P1075
      binding to SUR2B in a monophasic manner, with the exception of minoxidil sulfate,
      which induced a biphasic displacement. The affinities of KCO binding to SUR2B
      were 3.5-8-fold higher than their potencies for activation of SUR2B/KIR6.2
      channels. The results establish that SURs are the KCO receptors of KATP channels
      and suggest that KCO binding requires a conformational change induced by ATP
      hydrolysis in both NBFs.

PMID- 9755154
TI  - Importance of a flexible hinge near the motor domain in kinesin-driven motility.
AB  - Conventional kinesin is a molecular motor consisting of an N-terminal catalytic
      motor domain, an extended stalk and a small globular C-terminus. Whereas the
      structure and function of the catalytic motor domain has been investigated,
      little is known about the function of domains outside the globular head. A short
      coiled-coil region adjacent to the motor domain, termed the neck, is known to be
      important for dimerization and may be required for kinesin processivity. We now
      provide evidence that a helix-disrupting hinge region (hinge 1) that separates
      the neck from the first extended coiled-coil of the stalk plays an essential role
      in basic motor activity. A fast fungal kinesin from Syncephalastrum racemosum was
      used for these studies. Deletion, substitution by a coiled-coil and truncation of
      the hinge 1 region all reduce motor speed and uncouple ATP turnover from gliding
      velocity. Insertion of hinge 1 regions from two conventional kinesins, Nkin and
      DmKHC, fully restores motor activity, whereas insertion of putative flexible
      linkers of other proteins does not, suggesting that hinge 1 regions of
      conventional kinesins can functionally replace each other. We suggest that this
      region is essential for kinesin movement in its promotion of chemo-mechanical
      coupling of the two heads and therefore the functional motor domain should be
      redefined to include not only the catalytic head but also the adjacent neck and
      hinge 1 domains.

PMID- 9755155
TI  - Disulfide bond formation in the Escherichia coli cytoplasm: an in vivo role
      reversal for the thioredoxins.
AB  - Cytoplasmic proteins do not generally contain structural disulfide bonds,
      although certain cytoplasmic enzymes form such bonds as part of their catalytic
      cycles. The disulfide bonds in these latter enzymes are reduced in Escherichia
      coli by two systems; the thioredoxin pathway and the glutathione/glutaredoxin
      pathway. However, structural disulfide bonds can form in proteins in the
      cytoplasm when the gene (trxB) for the enzyme thioredoxin reductase is
      inactivated by mutation. This disulfide bond formation can be detected by
      assessing the state of the normally periplasmic enzyme alkaline phosphatase (AP)
      when it is localized to the cytoplasm. Here we show that the formation of
      disulfide bonds in cytoplasmic AP in the trxB mutant is dependent on the presence
      of two thioredoxins in the cell, thioredoxins 1 and 2, the products of the genes
      trxA and trxC, respectively. Our evidence supports a model in which the oxidized
      forms of these thioredoxins directly catalyze disulfide bond formation in
      cytoplasmic AP, a reversal of their normal role. In addition, we show that the
      recently discovered thioredoxin 2 can perform many of the roles of thioredoxin 1
      in vivo, and thus is able to reduce certain essential cytoplasmic enzymes. Our
      results suggest that the three most effective cytoplasmic disulfide-reducing
      proteins are thioredoxin 1, thioredoxin 2 and glutaredoxin 1; expression of any
      one of these is sufficient to support aerobic growth. Our results help to explain
      how the reducing environment in the cytoplasm is maintained so that disulfide
      bonds do not normally occur.

PMID- 9755156
TI  - The crystal structure of the processive endocellulase CelF of Clostridium
      cellulolyticum in complex with a thiooligosaccharide inhibitor at 2.0 A
      resolution.
AB  - The mesophilic bacterium Clostridium cellulolyticum exports multienzyme complexes
      called cellulosomes to digest cellulose. One of the three major components of the
      cellulosome is the processive endocellulase CelF. The crystal structure of the
      catalytic domain of CelF in complex with two molecules of a thiooligosaccharide
      inhibitor was determined at 2.0 A resolution. This is the first three-dimensional
      structure to be solved of a member of the family 48 glycosyl hydrolases. The
      structure consists of an (alpha alpha)6-helix barrel with long loops on the N
      terminal side of the inner helices, which form a tunnel, and an open cleft region
      covering one side of the barrel. One inhibitor molecule is enclosed in the
      tunnel, the other exposed in the open cleft. The active centre is located in a
      depression at the junction of the cleft and tunnel regions. Glu55 is the proposed
      proton donor in the cleavage reaction, while the corresponding base is proposed
      to be either Glu44 or Asp230. The orientation of the reducing ends of the
      inhibitor molecules together with the chain translation through the tunnel in the
      direction of the active centre indicates that CelF cleaves processively
      cellobiose from the reducing to the non-reducing end of the cellulose chain.

PMID- 9755157
TI  - A plasma membrane-bound putative endo-1,4-beta-D-glucanase is required for normal
      wall assembly and cell elongation in Arabidopsis.
AB  - Endo-1,4-beta-D-glucanases (EGases) form a large family of hydrolytic enzymes in
      prokaryotes and eukaryotes. In higher plants, potential substrates in vivo are
      xyloglucan and non-crystalline cellulose in the cell wall. Gene expression
      patterns suggest a role for EGases in various developmental processes such as
      leaf abscission, fruit ripening and cell expansion. Using Arabidopsis thaliana
      genetics, we demonstrate the requirement of a specialized member of the EGase
      family for the correct assembly of the walls of elongating cells. KORRIGAN (KOR)
      is identified by an extreme dwarf mutant with pronounced architectural
      alterations in the primary cell wall. The KOR gene was isolated and encodes a
      membrane-anchored member of the EGase family, which is highly conserved between
      mono- and dicotyledonous plants. KOR is located primarily in the plasma membrane
      and presumably acts at the plasma membrane-cell wall interface. KOR mRNA was
      found in all organs examined, and in the developing dark-grown hypocotyl, mRNA
      levels were correlated with rapid cell elongation. Among plant growth factors
      involved in the control of hypocotyl elongation (auxin, gibberellins and
      ethylene) none significantly influenced KOR-mRNA levels. However, reduced KOR
      mRNA levels were observed in det2, a mutant deficient for brassinosteroids.
      Although the in vivo substrate remains to be determined, the mutant phenotype is
      consistent with a central role for KOR in the assembly of the cellulose
      hemicellulose network in the expanding cell wall.

PMID- 9755158
TI  - Functional dissection of Arabidopsis COP1 reveals specific roles of its three
      structural modules in light control of seedling development.
AB  - Arabidopsis COP1 acts as a repressor of photomorphogenesis in darkness, and light
      stimuli abrogate the repressive ability and nuclear abundance of COP1. COP1 has
      three known structural modules: an N-terminal RING-finger, followed by a
      predicted coiled-coil and C-terminal WD-40 repeats. A systematic study was
      undertaken to dissect the functional roles of these three COP1 domains in light
      control of Arabidopsis seedling development. Our data suggest that COP1 acts
      primarily as a homodimer, and probably dimerizes through the coiled-coil domain.
      The RING-finger and the coiled-coil domains can function independently as light
      responsive modules mediating the light-controlled nucleocytoplasmic partitioning
      of COP1. The C-terminal WD-40 domain functions as an autonomous repressor module
      since the overexpression of COP1 mutant proteins with intact WD-40 repeats are
      able to suppress photomorphogenic development. This WD-40 domain-mediated
      repression can be at least in part accounted for by COP1's direct interaction
      with and negative regulation of HY5, a bZIP transcription factor that positively
      regulates photomorphogenesis. However, COP1 self-association is a prerequisite
      for the observed interaction of the COP1 WD-40 repeats with HY5. This work thus
      provides a structural basis of COP1 as a molecular switch.

PMID- 9755159
TI  - Coexpression of IL-6 and soluble IL-6R causes nodular regenerative hyperplasia
      and adenomas of the liver.
AB  - Studies with tumor necrosis factor p55 receptor- and interleukin-6 (IL-6)
      deficient mice have shown that IL-6 is required for hepatocyte proliferation and
      reconstitution of the liver mass after partial hepatectomy. The biological
      activities of IL-6 are potentiated when this cytokine binds soluble forms of its
      specific receptor subunit (sIL-6R) and the resulting complex interacts with the
      transmembrane signaling chain gp130. We show here that double transgenic mice
      expressing high levels of both human IL-6 and sIL-6R under the control of liver
      specific promoters spontaneously develop nodules of hepatocellular hyperplasia
      around periportal spaces and present signs of sustained hepatocyte proliferation.
      The resulting picture is identical to that of human nodular regenerative
      hyperplasia, a condition frequently associated with immunological and
      myeloproliferative disorders. In high expressors, hyperplastic lesions progress
      with time into discrete liver adenomas. These data strongly suggest that the IL
      6/sIL-6R complex is both a primary stimulus to hepatocyte proliferation and a
      pathogenic factor of hepatocellular transformation.

PMID- 9755160
TI  - alphaKAP is an anchoring protein for a novel CaM kinase II isoform in skeletal
      muscle.
AB  - Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) is present in a
      membrane-bound form that phosphorylates synapsin I on neuronal synaptic vesicles
      and the ryanodine receptor at skeletal muscle sarcoplasmic reticulum (SR), but it
      is unclear how this soluble enzyme is targeted to membranes. We demonstrate that
      alphaKAP, a non-kinase protein encoded by a gene within the gene of alpha-CaM
      kinase II, can target the CaM kinase II holoenzyme to the SR membrane. Our
      results indicate that alphaKAP (i) is anchored to the membrane via its N-terminal
      hydrophobic domain, (ii) can co-assemble with catalytically competent CaM kinase
      II isoforms and target them to the membrane regardless of their state of
      activation, and (iii) is co-localized and associated with rat skeletal muscle CaM
      kinase II in vivo. alphaKAP is therefore the first demonstrated anchoring protein
      for CaM kinase II. CaM kinase II assembled with alphaKAP retains normal enzymatic
      activity and the ability to become Ca2+-independent following
      autophosphorylation. A new variant of beta-CaM kinase II, termed betaM-CaM kinase
      II, is one of the predominant CaM kinase II isoforms associated with alphaKAP in
      skeletal muscle SR.

PMID- 9755161
TI  - Regulated nucleo/cytoplasmic exchange of HOG1 MAPK requires the importin beta
      homologs NMD5 and XPO1.
AB  - MAP kinase signaling modules serve to transduce extracellular signals to the
      nucleus of eukaryotic cells, but little is known about how signals cross the
      nuclear envelope. Exposure of yeast cells to increases in extracellular
      osmolarity activates the HOG1 MAP kinase cascade, which is composed of three
      tiers of protein kinases, namely the SSK2, SSK22 and STE11 MAPKKKs, the PBS2
      MAPKK, and the HOG1 MAPK. Using green fluorescent protein (GFP) fusions of these
      kinases, we found that HOG1, PBS2 and STE11 localize to the cytoplasm of
      unstressed cells. Following osmotic stress, HOG1, but neither PBS2 nor STE11,
      translocates into the nucleus. HOG1 translocation occurs very rapidly, is
      transient, and correlates with the phosphorylation and activation of the MAP
      kinase by its MAPKK. HOG1 phosphorylation is necessary and sufficient for nuclear
      translocation, because a catalytically inactive kinase when phosphorylated is
      translocated to the nucleus as efficiently as the wild-type. Nuclear import of
      the MAPK under stress conditions requires the activity of the small GTP binding
      protein Ran-GSP1, but not the NLS-binding importin alpha/beta heterodimer.
      Rather, HOG1 import requires the activity of a gene, NMD5, that encodes a novel
      importin beta homolog. Similarly, export of dephosphorylated HOG1 from the
      nucleus requires the activity of the NES receptor XPO1/CRM1. Our findings define
      the requirements for the regulated nuclear transport of a stress-activated MAP
      kinase.

PMID- 9755162
TI  - Stress-activated protein kinases are negatively regulated by cell density.
AB  - Stimulation by UV irradiation, TNFalpha, as well as PDGF or EGF activates the
      JNK/SAPK signalling pathway in mouse fibroblasts. This results in the
      phosphorylation of the N-terminal domain of c-Jun, increasing its transactivation
      potency. Using an antibody that specifically recognizes c-Jun phosphorylated at
      Ser63, we show that culture confluency drastically inhibited c-Jun N-terminal
      phosphorylation due to the inhibition of the JNK/SAPK pathway. Transfection
      experiments demonstrate that the inhibition occurs at the same level as, or
      upstream of, the small G-proteins cdc42 and Rac1. In contrast, the classical MAPK
      pathway was insensitive to confluency. The inhibition of JNK/SAPK activation
      depended on the integrity of the actin microfilament network. These results were
      confirmed and extended in monolayer wounding experiments. After PDGF, EGF or UV
      stimulation, c-Jun was predominantly phosphorylated in cells bordering the wound,
      which are the cells that move to occupy the wounded area. Thus, modulation of the
      stress-dependent signal cascade by confluency will restrict c-Jun N-terminal
      phosphorylation in response to mitogenic or chemotactic agents to cells that
      border a wounded area.

PMID- 9755163
TI  - The kinase Eg2 is a component of the Xenopus oocyte progesterone-activated
      signaling pathway.
AB  - Quiescent Xenopus oocytes are activated by progesterone, which binds to an
      unidentified surface-associated receptor. Progesterone activates a poorly
      understood signaling pathway that results in the translational activation of mRNA
      encoding Mos, a MAP kinase kinase kinase necessary for the activation of MAP
      kinase and MPF, the resumption of meiosis, and maturation of the oocyte into the
      sperm-responsive egg. We have designed a screen to identify early signaling
      proteins based on the premise that some of these proteins would be phosphorylated
      or otherwise modified within minutes of progesterone addition. This screen has
      revealed Eg2, a Ser/Thr kinase. We find that Eg2 is phosphorylated soon after
      progesterone stimulation and provide evidence that it functions in the signaling
      pathway. Overexpression of Eg2 via mRNA microinjection shortens the time between
      progesterone stimulation and the appearance of new Mos protein, accelerates
      activation of MAP kinase and advances entry into the meiotic cell cycle. Finally,
      overexpression of Eg2 dramatically reduces the concentration of progesterone
      needed to trigger oocyte activation. These results argue that the kinase Eg2 is a
      component of the progesterone-activated signaling pathway that releases frog
      oocytes from cell cycle arrest.

PMID- 9755164
TI  - Tec/Bmx non-receptor tyrosine kinases are involved in regulation of Rho and serum
      response factor by Galpha12/13.
AB  - A transient transfection system was used to identify regulators and effectors for
      Tec and Bmx, members of the Tec non-receptor tyrosine kinase family. We found
      that Tec and Bmx activate serum response factor (SRF), in synergy with
      constitutively active alpha subunits of the G12 family of GTP-binding proteins,
      in transiently transfected NIH 3T3 cells. The SRF activation is sensitive to C3,
      suggesting the involvement of Rho. The kinase and Tec homology (TH) domains of
      the kinases are required for SRF activation. In addition, kinase-deficient
      mutants of Bmx are able to inhibit Galpha13- and Galpha12-induced SRF activation,
      and to suppress thrombin-induced SRF activation in cells lacking Galphaq/11,
      where thrombin's effect is mediated by G12/13 proteins. Moreover, expression of
      Galpha12 and Galpha13 stimulates autophosphorylation and transphosphorylation
      activities of Tec. Thus, the evidence indicates that Tec kinases are involved in
      Galpha12/13-induced, Rho-mediated activation of SRF. Furthermore, Src, which was
      previously shown to activate kinase activities of Tec kinases, activates SRF
      predominantly in Rho-independent pathways in 3T3 cells, as shown by the fact that
      C3 did not block Src-mediated SRF activation. However, the Rho-dependent pathway
      becomes significant when Tec is overexpressed.

PMID- 9755165
TI  - A Nck-Pak1 signaling module is required for T-cell receptor-mediated activation
      of NFAT, but not of JNK.
AB  - The T-cell antigen receptor (TCR) triggers a signaling cascade initiated by the
      tyrosine kinase Lck and requiring the proto-oncogene p95(vav). Vav is activated
      by Lck and can function as a guanine nucleotide exchange factor for the Rho
      family GTPases, Rac1 and Cdc42. To investigate the involvement of these GTPases
      in TCR signaling, we focused on their well characterized effector, Pak1. This
      serine/threonine kinase is activated by GTP-bound Rac1 or Cdc42. However, its
      role in mediating downstream signaling events is controversial. We observed
      rapid, TCR-dependent activation of Pak1 and TCR-inducible association of Pak1
      with Nck, which was tyrosine phosphorylated following stimulation. Pak1
      activation occurred independently of Ras activation or calcium flux, but was
      dependent on the Lck tyrosine kinase, and was downstream of Vav and Cdc42.
      Dominant negative Pak1 or Nck specifically inhibited TCR-mediated activation of
      the nuclear factor of activated T cells (NFAT) transcription factor. TCR-mediated
      activation of Erk2 was also inhibited by dominant negative Pak. However, Pak1
      activation was neither necessary nor sufficient for TCR-dependent c-Jun N
      terminal kinase (JNK) activation. Therefore, Pak1 acts downstream of Vav and is
      required for activation of Erk2 and NFAT by a JNK-independent pathway. This is
      the first demonstration of a requirement for Pak to mediate the regulation of
      gene expression by an extracellular ligand.

PMID- 9755166
TI  - An essential protease involved in bacterial cell-cycle control.
AB  - Proteolytic inactivation of key regulatory proteins is essential in eukaryotic
      cell-cycle control. We have identified a protease in the eubacterium Caulobacter
      crescentus that is indispensable for viability and cell-cycle progression,
      indicating that proteolysis is also involved in controlling the bacterial cell
      cycle. Mutants of Caulobacter that lack the ATP-dependent serine protease ClpXP
      are arrested in the cell cycle before the initiation of chromosome replication
      and are blocked in the cell division process. ClpXP is composed of two types of
      polypeptides, the ClpX ATPase and the ClpP peptidase. Site-directed mutagenesis
      of the catalytically active serine residue of ClpP confirmed that the proteolytic
      activity of ClpXP is essential. Analysis of mutants lacking ClpX or ClpP revealed
      that both proteins are required in vivo for the cell-cycle-dependent degradation
      of the regulatory protein CtrA. CtrA is a member of the response regulator family
      of two-component signal transduction systems and controls multiple cell-cycle
      processes in Caulobacter. In particular, CtrA negatively controls DNA replication
      and our findings suggest that specific degradation of the CtrA protein by the
      ClpXP protease contributes to G1-to-S transition in this organism.

PMID- 9755167
TI  - The role of the destruction box and its neighbouring lysine residues in cyclin B
      for anaphase ubiquitin-dependent proteolysis in fission yeast: defining the D-box
      receptor.
AB  - Programmed proteolysis of proteins such as mitotic cyclins and Cut2/Pds1p
      requires a 9-residue conserved motif known as the destruction box (D-box). Strong
      expression of protein fragments containing destruction boxes, such as the first
      70 residues of Cdc13 (N70), inhibits the growth of Schizosaccharomyces pombe at
      metaphase. This inhibition can be overcome either by removal of all lysine
      residues from N70 using site-directed mutagenesis (K0-N70) or by raising the
      concentration of intracellular ubiquitin. Consistent with the idea that
      competition for ubiquitin accounts for some of its inhibitory effects, wild-type
      N70 not only stabilized D-box proteins, but also Rum1 and Cdc18, which are
      degraded by a different pathway. The K0-N70 construct was neither
      polyubiquitinated nor degraded in vitro, but it blocked the growth of strains of
      yeast in which anaphase-promoting complex/cyclosome (APC/C) function was
      compromised by mutation, and specifically inhibited proteolysis of APC/C
      substrates in vivo. Both K0-N70 and 20-residue D-box peptides blocked
      polyubiquitination of other D-box-containing substrates in a cell-free
      ubiquitination assay system. These data suggest the existence of a D-box receptor
      protein that recognizes D-boxes prior to ubiquitination.

PMID- 9755168
TI  - The budding yeast Rad9 checkpoint protein is subjected to Mec1/Tel1-dependent
      hyperphosphorylation and interacts with Rad53 after DNA damage.
AB  - The Saccharomyces cerevisiae RAD9 checkpoint gene is required for transient cell
      cycle arrests and transcriptional induction of DNA repair genes in response to
      DNA damage. Polyclonal antibodies raised against the Rad9 protein recognized
      several polypeptides in asynchronous cultures, and in cells arrested in S or G2/M
      phases while a single form was observed in G1-arrested cells. Treatment with
      various DNA damaging agents, i.e. UV, ionizing radiation or methyl methane
      sulfonate, resulted in the appearance of hypermodified forms of the protein. All
      modifications detected during a normal cell cycle and after DNA damage were
      sensitive to phosphatase treatment, indicating that they resulted from
      phosphorylation. Damage-induced hyperphosphorylation of Rad9 correlated with
      checkpoint functions (cell-cycle arrest and transcriptional induction) and was
      cell-cycle stage- and progression-independent. In asynchronous cultures, Rad9
      hyperphosphorylation was dependent on MEC1 and TEL1, homologues of the ATR and
      ATM genes. In G1-arrested cells, damage-dependent hyperphosphorylation required
      functional MEC1 in addition to RAD17, RAD24, MEC3 and DDC1, demonstrating cell
      cycle stage specificity of the checkpoint genes in this response to DNA damage.
      Analysis of checkpoint protein interactions after DNA damage revealed that Rad9
      physically associates with Rad53.

PMID- 9755169
TI  - Cdc18 transcription and proteolysis couple S phase to passage through mitosis.
AB  - In fission yeast, cdc18p plays a critical role in bringing about the onset of S
      phase. We show that cdc18p expression is subject to a complex sequence of cell
      cycle controls which ensure that cdc18p levels rise dramatically as cells exit
      mitosis, before the appearance of CDK activity in G1. We find that transcription
      of cdc18, together with the transcription of other cdc10p/res1p targets, is first
      initiated as cells enter mitosis and continues even in cells arrested in mitosis
      with highly condensed chromatin. However, cdc18p cannot accumulate during mitosis
      because it is targeted for proteolysis by mitotic cdc2p-protein kinase-mediated
      phosphorylation. On exit from mitosis, the cdc2p mitotic kinase activity falls,
      stabilizing cdc18p, which then rapidly accumulates. This combination of mitotic
      transcription and CDK-mediated proteolysis ensures that progression through
      mitosis simultaneously prepares cells for DNA replication. During S phase, cdc18
      transcription is then switched off, preventing the re-initiation of DNA synthesis
      until the completion of the next round of mitosis.

PMID- 9755170
TI  - Xenopus Cdc45-dependent loading of DNA polymerase alpha onto chromatin under the
      control of S-phase Cdk.
AB  - At the onset of S phase, chromosomal replication is initiated by the loading of
      DNA polymerase alpha onto replication origins. However, the molecular mechanisms
      for controlling the initiation are poorly understood. Using Xenopus egg extract,
      we report here the identification of a Xenopus homolog of Cdc45, a yeast protein
      essential for the initiation of replication, which is shown to be an essential
      molecule for the initiation of replication via the loading of DNA polymerase
      alpha onto chromatin. XCdc45, by physically interacting with the polymerase in
      the extract, became associated with chromatin only after nuclear formation.
      During S phase, XCdc45 co-localized with the polymerase in the nuclei, and the
      loading of the polymerase, which depended on endogenous XCdc45, was facilitated
      by exogenously added recombinant XCdc45. These findings, together with the
      apparent requirement of S-phase-cdk activity for the loading of XCdc45, suggest
      that XCdc45, under the control of S-phase cdk, plays a pivotal role in the
      loading of DNA polymerase alpha onto chromatin.

PMID- 9755171
TI  - Cloning of mammalian Ire1 reveals diversity in the ER stress responses.
AB  - Cells modify their gene expression pattern in response to stress signals
      emanating from the endoplasmic reticulum (ER). The well-characterized aspect of
      this response consists of the activation of genes that encode protein chaperones
      and other ER resident proteins, and is conserved between mammals and yeast. In
      mammalian cells, however, ER stress also activates other pathways, including the
      expression of the transcription factor CHOP/GADD153 and its downstream target
      genes. ER stress is also linked to the development of programmed cell death, a
      phenomenon in which CHOP plays an important role. Here we report on the cloning
      of a murine homolog of yeast IRE1, an essential upstream component of the ER
      stress-response in yeast. The mammalian Ire1 is located in the ER membrane and
      its over-expression in mammalian cells activates both the endogenous ER chaperone
      GRP78/BiP and CHOP-encoding genes. Over-expression of a dominant-negative form of
      Ire1 blocks the induction of GRP78/BiP and CHOP in response to the ER stress
      induced by tunicamycin treatment. Over-expression of murine Ire1 also leads to
      the development of programmed cell death in transfected cells. These results
      indicate that a single upstream component, Ire1, plays a role in multiple facets
      of the ER stress-response in mammalian cells.

PMID- 9755172
TI  - A new long form of Sox5 (L-Sox5), Sox6 and Sox9 are coexpressed in chondrogenesis
      and cooperatively activate the type II collagen gene.
AB  - Transcripts for a new form of Sox5, called L-Sox5, and Sox6 are coexpressed with
      Sox9 in all chondrogenic sites of mouse embryos. A coiled-coil domain located in
      the N-terminal part of L-Sox5, and absent in Sox5, showed >90% identity with a
      similar domain in Sox6 and mediated homodimerization and heterodimerization with
      Sox6. Dimerization of L-Sox5/Sox6 greatly increased efficiency of binding of the
      two Sox proteins to DNA containing adjacent HMG sites. L-Sox5, Sox6 and Sox9
      cooperatively activated expression of the chondrocyte differentiation marker
      Col2a1 in 10T1/2 and MC615 cells. A 48 bp chondrocyte-specific enhancer in this
      gene, which contains several HMG-like sites that are necessary for enhancer
      activity, bound the three Sox proteins and was cooperatively activated by the
      three Sox proteins in non-chondrogenic cells. Our data suggest that L-Sox5/Sox6
      and Sox9, which belong to two different classes of Sox transcription factors,
      cooperate with each other in expression of Col2a1 and possibly other genes of the
      chondrocytic program.

PMID- 9755173
TI  - Identification of Bach2 as a B-cell-specific partner for small maf proteins that
      negatively regulate the immunoglobulin heavy chain gene 3' enhancer.
AB  - Maf family transcription factors are important regulators in various
      differentiation systems. Putative Maf recognition elements (MAREs) are found in
      the 3' enhancer region of the immunoglobulin heavy chain (IgH) gene. These
      elements are bound in B-cell extracts by a heterodimeric protein complex
      containing both Bach2 and a small Maf protein. Analysis of normal hematopoietic
      cells revealed that Bach2 is specifically expressed in B cells. Bach2 is
      abundantly expressed in the early stages of B-cell differentiation and turned off
      in terminally differentiated cells. Bach2 acts together with MafK as a negative
      effector of the IgH 3' enhancer and binds to the co-repressor SMRT (silencing
      mediator of retinoid and thyroid receptor). Hence the Bach2-small-Maf heterodimer
      may represent the first example of a B-cell lineage, and of a developmental stage
      restricted negative effector of the MARE in the IgH 3' enhancer region.

PMID- 9755175
TI  - Srb/mediator proteins interact functionally and physically with transcriptional
      repressor Sfl1.
AB  - Srb/mediator proteins that are associated with RNA polymerase II holoenzyme have
      been implicated in transcriptional repression in Saccharomyces cerevisiae. We
      show here that the defect in repression of SUC2 caused by mutation of SRB8, SRB9,
      SRB11, SIN4 or ROX3 is suppressed by increased dosage of the SFL1 gene, and the
      genetic behavior of the sfl1Delta mutation provides further evidence for a
      functional relationship. Sfl1 acts on SUC2 through a repression site located
      immediately 5' to the TATA box, and Sfl1 binds this DNA sequence in vitro.
      Moreover, LexA-Sfl1 represses transcription of a reporter, and repression is
      reduced in an srb9 mutant. Finally, we show that Sfl1 co-immunoprecipitates from
      cell extracts with Srb9, Srb11, Sin4 and Rox3. We propose that Sfl1, when bound
      to its site, interacts with Srb/mediator proteins to inhibit transcription by RNA
      polymerase II holoenzyme.

PMID- 9755174
TI  - Expression of the LIM-homeobox gene LH2 generates immortalized steel factor
      dependent multipotent hematopoietic precursors.
AB  - The genes controlling self-renewal and differentiation in the hematopoietic
      system are largely unknown. The LIM-homeobox genes are known to be important for
      asymmetric cell divisions and differentiation of specific cell types and organs.
      One member of this family, LH2, is expressed in fetal liver at the time of active
      hematopoiesis. Therefore, we have assessed the function of LH2 during the
      formation and initial expansion of the hematopoietic system by differentiating
      LH2-transduced embryonic stem (ES) cells in vitro. This procedure generated
      multipotent hematopoietic precursor cell (HPC) lines that required Steel factor
      for growth. HPC lines have been maintained in an undifferentiated state in
      culture for >7 months. Other growth factors tested efficiently induce terminal
      differentiation of HPCs into various mature myeloid lineages. Steel factor is
      also required and acts synergistically with the other growth factors to generate
      multilineage colonies from the HPCs. These HPC lines express transcription
      factors that are consistent with an immature progenitor, and the pattern of cell
      surface marker expression is similar to that of early fetal multipotent
      hematopoietic progenitors. Collectively, these data suggest that the HPC lines
      represent an early fetal multipotent hematopoietic progenitor, and suggest a role
      for LH2 in the control of cell fate decision and/or proliferation in the
      hematopoietic system.

PMID- 9755176
TI  - Kruppel acts as a developmental switch gene that mediates Notch signalling
      dependent tip cell differentiation in the excretory organs of Drosophila.
AB  - Cell proliferation in the excretory organs of Drosophila, the Malpighian tubules
      (MT), is under the control of a neural tip cell. This unique cell is singled out
      from equivalent MT primordial cells in response to Notch signalling. We show that
      the gene Kruppel (Kr), best known for its segmentation function in the early
      embryo, is under the control of the Notch-dependent signalling process. Lack-of
      function and gain-of-function experiments demonstrate that Kr activity determines
      the neural fate of tip cells by acting as a direct downstream target of proneural
      basic helix-loop-helix (bHLH) proteins that are restricted in response to Notch
      signalling. We have identified a unique cis-acting element that mediates all
      spatial and temporal aspects of Kr gene expression during MT development. This
      element contains functional binding sites for the restricted proneural bHLH
      factors and Fork head protein which is expressed in all MT cells. Our results
      suggest a mechanism in which these transcription factors cooperate to set up a
      unique cell fate within an equivalence group of cells by restricting the activity
      of the developmental switch gene Kr in response to Notch signalling.

PMID- 9755177
TI  - sigmaR, an RNA polymerase sigma factor that modulates expression of the
      thioredoxin system in response to oxidative stress in Streptomyces coelicolor
      A3(2).
AB  - We have identified an RNA polymerase sigma factor, sigmaR, that is part of a
      system that senses and responds to thiol oxidation in the Gram-positive,
      antibiotic-producing bacterium Streptomyces coelicolor A3(2). Deletion of the
      gene (sigR) encoding sigmaR caused sensitivity to the thiol-specific oxidant
      diamide and to the redox cycling compounds menadione and plumbagin. This
      correlated with reduced levels of disulfide reductase activity and an inability
      to induce this activity on exposure to diamide. The trxBA operon, encoding
      thioredoxin reductase and thioredoxin, was found to be under the direct control
      of sigmaR. trxBA is transcribed from two promoters, trxBp1 and trxBp2, separated
      by 5-6 bp. trxBp1 is transiently induced at least 50-fold in response to diamide
      treatment in a sigR-dependent manner. Purified sigmaR directed transcription from
      trxBp1 in vitro, indicating that trxBp1 is a target for sigmaR. Transcription of
      sigR itself initiates at two promoters, sigRp1 and sigRp2, which are separated by
      173 bp. The sigRp2 transcript was undetectable in a sigR-null mutant, and
      purified sigmaR could direct transcription from sigRp2 in vitro, indicating that
      sigR is positively autoregulated. Transcription from sigRp2 was also transiently
      induced (70-fold) following treatment with diamide. We propose a model in which
      sigmaR induces expression of the thioredoxin system in response to cytoplasmic
      disulfide bond formation. Upon reestablishment of normal thiol levels, sigmaR
      activity is switched off, resulting in down-regulation of trxBA and sigR. We
      present evidence that the sigmaR system also functions in the actinomycete
      pathogen Mycobacterium tuberculosis.

PMID- 9755178
TI  - Modifications of U2 snRNA are required for snRNP assembly and pre-mRNA splicing.
AB  - Among the spliceosomal snRNAs, U2 has the most extensive modifications, including
      a 5' trimethyl guanosine (TMG) cap, ten 2'-O-methylated residues and 13
      pseudouridines. At short times after injection, cellularly derived (modified) U2
      but not synthetic (unmodified) U2 rescues splicing in Xenopus oocytes depleted of
      endogenous U2 by RNase H targeting. After prolonged reconstitution, synthetic U2
      regenerates splicing activity; a correlation between the extent of U2
      modification and U2 function in splicing is observed. Moreover, 5-fluorouridine
      containing U2 RNA, a potent inhibitor of U2 pseudouridylation, specifically
      abolishes rescue by synthetic U2, while rescue by cellularly derived U2 is not
      affected. By creating chimeric U2 molecules in which some sequences are from
      cellularly derived U2 and others are from in vitro transcribed U2, we demonstrate
      that the functionally important modifications reside within the 27 nucleotides at
      the 5' end of U2. We further show that 2'-O-methylation and pseudouridylation
      activities reside in the nucleus and that the 5' TMG cap is not necessary for
      internal modification but is crucial for splicing activity. Native gel analysis
      reveals that unmodified U2 is not incorporated into the spliceosome. Examination
      of the U2 protein profile and glycerol-gradient analysis argue that U2
      modifications directly contribute to conversion of the 12S to the 17S U2 snRNP
      particle, which is essential for spliceosome assembly.

PMID- 9755179
TI  - Accumulation of mitochondrially synthesized Saccharomyces cerevisiae Cox2p and
      Cox3p depends on targeting information in untranslated portions of their mRNAs.
AB  - The essential products of the yeast mitochondrial translation system are seven
      hydrophobic membrane proteins and Var1p, a hydrophilic protein in the small
      ribosomal subunit. Translation of the membrane proteins depends on nuclearly
      encoded, mRNA-specific translational activators that recognize the 5'
      untranslated leaders of their target mRNAs. These translational activators are
      themselves membrane associated and could therefore tether translation to the
      inner membrane. In this study, we tested whether chimeric mRNAs with the
      untranslated sequences normally present on the mRNA encoding soluble Var1p, can
      direct functional expression of coding sequences specifying the integral membrane
      proteins Cox2p and Cox3p. DNA sequences specifying these chimeric mRNAs were
      inserted into mtDNA at the VAR1 locus and expressed in strains containing a
      nuclearly localized plasmid that supplies a functional form of Var1p, imported
      from the cytoplasm. Although cells expressing these chimeric mRNAs actively
      synthesized both membrane proteins, they were severely deficient in cytochrome c
      oxidase activity and in the accumulation of Cox2p and Cox3p, respectively. These
      data strongly support the physiological importance of interactions between
      membrane-bound mRNA-specific translational activators and the native 5'
      untranslated leaders of the COX2 and COX3 mRNAs for localizing productive
      synthesis of Cox2p and Cox3p to the inner membrane.

PMID- 9755180
TI  - Mechanism of inhibition of Psi+ prion determinant propagation by a mutation of
      the N-terminus of the yeast Sup35 protein.
AB  - The SUP35 gene of Saccharomyces cerevisiae encodes the polypeptide chain release
      factor eRF3. This protein (also called Sup35p) is thought to be able to undergo a
      heritable conformational switch, similarly to mammalian prions, giving rise to
      the cytoplasmically inherited Psi+ determinant. A dominant mutation (PNM2 allele)
      in the SUP35 gene causing a Gly58-->Asp change in the Sup35p N-terminal domain
      eliminates Psi+. Here we observed that the mutant Sup35p can be converted to the
      prion-like form in vitro, but such conversion proceeds slower than that of wild
      type Sup35p. The overexpression of mutant Sup35p induced the de novo appearance
      of Psi+ cells containing the prion-like form of mutant Sup35p, which was able to
      transmit its properties to wild-type Sup35p both in vitro and in vivo. Our data
      indicate that this Psi+-eliminating mutation does not alter the initial binding
      of Sup35p molecules to the Sup35p Psi+-specific aggregates, but rather inhibits
      its subsequent prion-like rearrangement and/or binding of the next Sup35p
      molecule to the growing prion-like Sup35p aggregate.

PMID- 9755181
TI  - Rotavirus RNA-binding protein NSP3 interacts with eIF4GI and evicts the poly(A)
      binding protein from eIF4F.
AB  - Most eukaryotic mRNAs contain a 5'cap structure and a 3'poly(A) sequence that
      synergistically increase the efficiency of translation. Rotavirus mRNAs are
      capped, but lack poly(A) sequences. During rotavirus infection, the viral protein
      NSP3A is bound to the viral mRNAs 3' end. We looked for cellular proteins that
      could interact with NSP3A, using the two-hybrid system in yeast. Screening a CV1
      cell cDNA library allowed us to isolate a partial cDNA of the human eukaryotic
      initiation factor 4GI (eIF4GI). The interaction of NSP3A with eIF4GI was
      confirmed in rotavirus infected cells by co-immunoprecipitation and in vitro with
      NSP3A produced in Escherichia coli. In addition, we show that the amount of
      poly(A) binding protein (PABP) present in eIF4F complexes decreases during
      rotavirus infection, even though eIF4A and eIF4E remain unaffected. PABP is
      removed from the eIF4F complex after incubation in vitro with the C-terminal part
      of NSP3A, but not with its N-terminal part produced in E.coli. These results show
      that a physical link between the 5' and the 3' ends of mRNA is necessary for the
      efficient translation of viral mRNAs and strongly support the closed loop model
      for the initiation of translation. These results also suggest that NSP3A, by
      taking the place of PABP on eIF4GI, is responsible for the shut-off of cellular
      protein synthesis.

PMID- 9755182
TI  - Host proteins can stimulate Tn7 transposition: a novel role for the ribosomal
      protein L29 and the acyl carrier protein.
AB  - The bacterial transposon Tn7 is distinguished by its ability to insert at a high
      frequency into a specific site in the Escherichia coli chromosome called attTn7.
      Tn7 insertion into attTn7 requires four Tn7-encoded transposition proteins: TnsA,
      TnsB, TnsC and TnsD. The selection of attTn7 is determined by TnsD, a sequence
      specific DNA-binding protein. TnsD binds attTn7 and interacts with TnsABC, the
      core transposition machinery, which facilitates the insertion of Tn7 into attTn7.
      In this work, we report the identification of two host proteins, the ribosomal
      protein L29 and the acyl carrier protein (ACP), which together stimulate the
      binding of TnsD to attTn7. The combination of L29 and ACP also stimulates Tn7
      transposition in vitro. Interestingly, mutations in L29 drastically decrease Tn7
      transposition in vivo, and this effect of L29 on Tn7 transposition is specific
      for TnsABC+D reactions.

PMID- 9755184
TI  - RNA-dependent activation of primer RNA production by influenza virus polymerase:
      different regions of the same protein subunit constitute the two required RNA
      binding sites.
AB  - The capped RNA primers required for the initiation of influenza virus mRNA
      synthesis are produced by the viral polymerase itself, which consists of three
      proteins PB1, PB2 and PA. Production of primers is activated only when the 5'-
      and 3'-terminal sequences of virion RNA (vRNA) bind sequentially to the
      polymerase, indicating that vRNA molecules function not only as templates for
      mRNA synthesis but also as essential cofactors which activate catalytic
      functions. Using thio U-substituted RNA and UV crosslinking, we demonstrate that
      the 5' and 3' sequences of vRNA bind to different amino acid sequences in the
      same protein subunit, the PB1 protein. Mutagenesis experiments proved that these
      two amino acid sequences constitute the functional RNA-binding sites. The 5'
      sequence of vRNA binds to an amino acid sequence centered around two arginine
      residues at positions 571 and 572, causing an allosteric alteration which
      activates two new functions of the polymerase complex. In addition to the PB2
      protein subunit acquiring the ability to bind 5'-capped ends of RNAs, the PB1
      protein itself acquires the ability to bind the 3' sequence of vRNA, via a
      ribonucleoprotein 1 (RNP1)-like motif, amino acids 249-256, which contains two
      phenylalanine residues required for binding. Binding to this site induces a
      second allosteric alteration which results in the activation of the endonuclease
      that produces the capped RNA primers needed for mRNA synthesis. Hence, the PB1
      protein plays a central role in the catalytic activity of the viral polymerase,
      not only in the catalysis of RNA-chain elongation but also in the activation of
      the enzyme activities that produce capped RNA primers.

PMID- 9755183
TI  - Sequence specificity of viral end DNA binding by HIV-1 integrase reveals critical
      regions for protein-DNA interaction.
AB  - HIV-1 integrase specifically recognizes and cleaves viral end DNA during the
      initial step of retroviral integration. The protein and DNA determinants of the
      specificity of viral end DNA binding have not been clearly identified. We have
      used mutational analysis of the viral end LTR sequence, in vitro selection of
      optimal viral end sequences, and specific photocrosslinking to identify regions
      of integrase that interact with specific bases in the LTR termini. The results
      highlight the involvement of the disordered loop of the integrase core domain,
      specifically residues Q148 and Y143, in binding to the terminal portion of the
      viral DNA ends. Additionally, we have identified positions upstream in the LTR
      termini which interact with the C-terminal domain of integrase, providing
      evidence for the role of that domain in stabilization of viral DNA binding.
      Finally, we have located a region centered 12 bases from the viral DNA terminus
      which appears essential for viral end DNA binding in the presence of magnesium,
      but not in the presence of manganese, suggesting a differential effect of
      divalent cations on sequence-specific binding. These results help to define
      important regions of contact between integrase and viral DNA, and assist in the
      formulation of a molecular model of this vital interaction.

PMID- 9755185
TI  - An extract from "Memoirs for family and friends".

PMID- 9755186
TI  - Sex and the evolution of intrahost competition in RNA virus phi6.
AB  - Sex allows beneficial mutations that occur in separate lineages to be fixed in
      the same genome. For this reason, the Fisher-Muller model predicts that
      adaptation to the environment is more rapid in a large sexual population than in
      an equally large asexual population. Sexual reproduction occurs in populations of
      the RNA virus phi6 when multiple bacteriophages coinfect the same host cell.
      Here, we tested the model's predictions by determining whether sex favors more
      rapid adaptation of phi6 to a bacterial host, Pseudomonas phaseolicola. Replicate
      populations of phi6 were allowed to evolve in either the presence or absence of
      sex for 250 generations. All experimental populations showed a significant
      increase in fitness relative to the ancestor, but sex did not increase the rate
      of adaptation. Rather, we found that the sexual and asexual treatments also
      differ because intense intrahost competition between viruses occurs during
      coinfection. Results showed that the derived sexual viruses were selectively
      favored only when coinfection is common, indicating that within-host competition
      detracts from the ability of viruses to exploit the host. Thus, sex was not
      advantageous because the cost created by intrahost competition was too strong.
      Our findings indicate that high levels of coinfection exceed an optimum where sex
      may be beneficial to populations of phi6, and suggest that genetic conflicts can
      evolve in RNA viruses.

PMID- 9755187
TI  - Mechanism and control of interspecies recombination in Escherichia coli. I.
      Mismatch repair, methylation, recombination and replication functions.
AB  - A genetic analysis of interspecies recombination in Escherichia coli between the
      linear Hfr DNA from Salmonella typhimurium and the circular recipient chromosome
      reveals some fundamental aspects of recombination between related DNA sequences.
      The MutS and MutL mismatch binding proteins edit (prevent) homeologous
      recombination between these 16% diverged genomes by at least two distinct
      mechanisms. One is MutH independent and presumably acts by aborting the initiated
      recombination through the UvrD helicase activity. The RecBCD nuclease might
      contribute to this editing step, presumably by preventing reiterated initiations
      of recombination at a given locus. The other editing mechanism is MutH dependent,
      requires unmethylated GATC sequences, and probably corresponds to an incomplete
      long-patch mismatch repair process that does not depend on UvrD helicase
      activity. Insignificant effects of the Dam methylation of parental DNAs suggest
      that unmethylated GATC sequences involved in the MutH-dependent editing are newly
      synthesized in the course of recombination. This hypothetical, recombination
      associated DNA synthesis involves PriA and RecF functions, which, therefore,
      determine the extent of MutH effect on interspecies recombination. Sequence
      divergence of recombining DNAs appears to limit the frequency, length, and
      stability of early heteroduplex intermediates, which can be stabilized, and the
      recombinants mature via the initiation of DNA replication.

PMID- 9755188
TI  - Reassigning cysteine in the genetic code of Escherichia coli.
AB  - We investigated directed deviations from the universal genetic code. Mutant tRNAs
      that incorporate cysteine at positions corresponding to the isoleucine AUU, AUC,
      and AUA and methionine AUG codons were introduced in Escherichia coli K12.
      Missense mutations at the cysteine catalytic site of thymidylate synthase were
      systematically crossed with synthetic suppressor tRNACys genes coexpressed from
      compatible plasmids. Strains harboring complementary codon/anticodon associations
      could be stably propagated as thymidine prototrophs. A plasmid-encoded tRNACys
      reading the codon AUA persisted for more than 500 generations in a strain
      requiring its suppressor activity for thymidylate biosynthesis, but was
      eliminated from a strain not requiring it. Cysteine miscoding at the codon AUA
      was also enforced in the active site of amidase, an enzyme found in Helicobacter
      pylori and not present in wild-type E. coli. Propagating the amidase missense
      mutation in E. coli with an aliphatic amide as nitrogen source required the
      overproduction of Cys-tRNA synthetase together with the complementary suppressor
      tRNACys. The toxicity of cysteine miscoding was low in all our strains. The small
      size and amphiphilic character of this amino acid may render it acceptable as a
      replacement at most protein positions and thus apt to overcome the steric and
      polar constraints that limit evolution of the genetic code.

PMID- 9755189
TI  - The Schizosaccharomyces pombe cho1+ gene encodes a phospholipid
      methyltransferase.
AB  - The isolation of mutants of Schizosaccharomyces pombe defective in the synthesis
      of phosphatidylcholine via the methylation of phosphatidylethanolamine is
      reported. These mutants are choline auxotrophs and fall into two unlinked
      complementation groups, cho1 and cho2. We also report the analysis of the cho1+
      gene, the first structural gene encoding a phospholipid biosynthetic enzyme from
      S. pombe to be cloned and characterized. The cho1+ gene disruption mutant
      (cho1Delta) is viable if choline is supplied and resembles the cho1 mutants
      isolated after mutagenesis. Sequence analysis of the cho1+ gene indicates that it
      encodes a protein closely related to phospholipid methyltransferases from
      Saccharomyces cerevisiae and rat. Phospholipid methyltransferases encoded by a
      rat liver cDNA and the S. cerevisiae OPI3 gene are both able to complement the
      choline auxotrophy of the S. pombe cho1 mutants. These results suggest that both
      the structure and function of the phospholipid N-methyltransferases are broadly
      conserved among eukaryotic organisms.

PMID- 9755190
TI  - Histone deacetylase homologs regulate epigenetic inheritance of transcriptional
      silencing and chromosome segregation in fission yeast.
AB  - Position-effect control at the silent mat2-mat3 interval and at centromeres and
      telomeres in fission yeast is suggested to be mediated through the assembly of
      heterochromatin-like structures. Therefore, trans-acting genes that affect
      silencing may encode either chromatin proteins, factors that modify them, or
      factors that affect chromatin assembly. Here, we report the identification of an
      essential gene, clr6 (cryptic loci regulator), which encodes a putative histone
      deacetylase that when mutated affects epigenetically maintained repression at the
      mat2-mat3 region and at centromeres and reduces the fidelity of chromosome
      segregation. Furthermore, we show that the Clr3 protein, when mutated, alleviates
      recombination block at mat region as well as silencing at donor loci and at
      centromeres and telomeres, also shares strong homology to known histone
      deacetylases. Genetic analyses indicate that silencing might be regulated by at
      least two overlapping histone deacetylase activities. We also found that
      transient inhibition of histone deacetylase activity by trichostatin A results in
      the increased missegregation of chromosomes in subsequent generations and,
      remarkably, alters the imprint at the mat locus, causing the heritable conversion
      of the repressed epigenetic state to the expressed state. This work supports the
      model that the level of histone deacetylation has a role in the assembly of
      repressive heterochromatin and provides insight into the mechanism of epigenetic
      inheritance.

PMID- 9755191
TI  - An arf1Delta synthetic lethal screen identifies a new clathrin heavy chain
      conditional allele that perturbs vacuolar protein transport in Saccharomyces
      cerevisiae.
AB  - ADP-ribosylation factor (ARF) is a small GTP-binding protein that is thought to
      regulate the assembly of coat proteins on transport vesicles. To identify factors
      that functionally interact with ARF, we have performed a genetic screen in
      Saccharomyces cerevisiae for mutations that exhibit synthetic lethality with an
      arf1Delta allele and defined seven genes by complementation tests (SWA1-7 for
      synthetically lethal with arf1Delta). Most of the swa mutants exhibit phenotypes
      comparable to arf1Delta mutants such as temperature-conditional growth,
      hypersensitivity to fluoride ions, and partial protein transport and
      glycosylation defects. Here, we report that swa5-1 is a new temperature-sensitive
      allele of the clathrin heavy chain gene (chc1-5), which carries a frameshift
      mutation near the 3' end of the CHC1 open reading frame. This genetic interaction
      between arf1 and chc1 provides in vivo evidence for a role for ARF in clathrin
      coat assembly. Surprisingly, strains harboring chc1-5 exhibited a significant
      defect in transport of carboxypeptidase Y or carboxypeptidase S to the vacuole
      that was not observed in other chc1 ts mutants. The kinetics of invertase
      secretion or transport of alkaline phosphatase to the vacuole were not
      significantly affected in the chc1-5 mutant, further implicating clathrin
      specifically in the Golgi to vacuole transport pathway for carboxypeptidase Y.

PMID- 9755192
TI  - Alteration of N-terminal phosphoesterase signature motifs inactivates
      Saccharomyces cerevisiae Mre11.
AB  - Saccharomyces cerevisiae Mre11, Rad50, and Xrs2 function in a protein complex
      that is important for nonhomologous recombination. Null mutants of MRE11, RAD50,
      and XRS2 are characterized by ionizing radiation sensitivity and mitotic
      interhomologue hyperrecombination. We mutagenized the four highly conserved
      phosphoesterase signature motifs of Mre11 to create mre11-11, mre11-2, mre11-3,
      and mre11-4 and assessed the functional consequences of these mutant alleles with
      respect to mitotic interhomologue recombination, chromosome loss, ionizing
      radiation sensitivity, double-strand break repair, and protein interaction. We
      found that mre11 mutants that behaved as the null were sensitive to ionizing
      radiation and deficient in double-strand break repair. We also observed that
      these null mutants exhibited a hyperrecombination phenotype in mitotic cells,
      consistent with previous reports, but did not exhibit an increased frequency of
      chromosome loss. Differential ionizing radiation sensitivities among the
      hypomorphic mre11 alleles correlated with the trends observed in the other
      phenotypes examined. Two-hybrid interaction testing showed that all but one of
      the mre11 mutations disrupted the Mre11-Rad50 interaction. Mutagenesis of the
      phosphoesterase signatures in Mre11 thus demonstrated the importance of these
      conserved motifs for recombinational DNA repair.

PMID- 9755193
TI  - Mutations in the membrane anchor of yeast cytochrome c1 compensate for the
      absence of Oxa1p and generate carbonate-extractable forms of cytochrome c1.
AB  - Oxa1p is a mitochondrial inner membrane protein that is mainly required for the
      insertion/assembly of complex IV and ATP synthase and is functionally conserved
      in yeasts, humans, and plants. We have isolated several independent suppressors
      that compensate for the absence of Oxa1p. Molecular cloning and sequencing reveal
      that the suppressor mutations (CYT1-1 to -6) correspond to amino acid
      substitutions that are all located in the membrane anchor of cytochrome c1 and
      decrease the hydrophobicity of this anchor. Cytochrome c1 is a catalytic subunit
      of complex III, but the CYT1-1 mutation does not seem to affect the electron
      transfer activity. The double-mutant cyt1-1,164, which has a drastically reduced
      electron transfer activity, still retains the suppressor activity. Altogether,
      these results suggest that the suppressor function of cytochrome c1 is
      independent of its electron transfer activity. In addition to the membrane-bound
      cytochrome c1, carbonate-extractable forms accumulate in all the suppressor
      strains. We propose that these carbonate-extractable forms of cytochrome c1 are
      responsible for the suppressor function by preventing the degradation of the
      respiratory complex subunits that occur in the absence of Oxa1p.

PMID- 9755195
TI  - Regulation of gene expression during the vegetative incompatibility reaction in
      Podospora anserina. Characterization of three induced genes.
AB  - Vegetative incompatibility in fungi limits the formation of viable heterokaryons.
      It results from the coexpression of incompatible genes in the heterokaryotic
      cells and leads to a cell death reaction. In Podospora anserina, a modification
      of gene expression takes place during this reaction, including a strong decrease
      of total RNA synthesis and the appearance of a new set of proteins. Using in
      vitro translation of mRNA and separation of protein products by two-dimensional
      gel electrophoresis, we have shown that the mRNA content of cells is
      qualitatively modified during the progress of the incompatibility reaction. Thus,
      gene expression during vegetative incompatibility is regulated, at least in part,
      by variation of the mRNA content of specific genes. A subtractive cDNA library
      enriched in sequences preferentially expressed during incompatibility was
      constructed. This library was used to identify genomic loci corresponding to
      genes whose mRNA is induced during incompatibility. Three such genes were
      characterized and named idi genes for genes induced during incompatibility. Their
      expression profiles suggest that they may be involved in different steps of the
      incompatibility reaction. The putative IDI proteins encoded by these genes are
      small proteins with signal peptides. IDI-2 protein is a cysteine-rich protein.
      IDI-2 and IDI-3 proteins display some similarity in a tryptophan-rich region.

PMID- 9755194
TI  - Identification of high-copy disruptors of telomeric silencing in Saccharomyces
      cerevisiae.
AB  - The ends of chromosomes in Saccharomyces cerevisiae initiate a repressive
      chromatin structure that spreads internally and inhibits the transcription of
      nearby genes, a phenomenon termed telomeric silencing. To investigate the
      molecular basis of this process, we carried out a genetic screen to identify
      genes whose overexpression disrupts telomeric silencing. We thus isolated 10 DOT
      genes (disruptor of telomeric silencing). Among these were genes encoding
      chromatin component Sir4p, DNA helicase Dna2p, ribosomal protein L32, and two
      proteins of unknown function, Asf1p and Ifh1p. The collection also included genes
      that had not previously been identified: DOT1, DOT4, DOT5, DOT6, and TLC1, which
      encodes the RNA template component of telomerase. With the exception of TLC1, all
      these genes, particularly DOT1 and DOT4, also reduced silencing at other
      repressed loci (HM loci and rDNA) when overexpressed. Moreover, deletion of the
      latter two genes weakened silencing as well, suggesting that DOT1 and DOT4
      normally play important roles in gene repression. DOT1 deletion also affected
      telomere tract length. The function of Dot1p is not known. The sequence of Dot4p
      suggests that it is a ubiquitin-processing protease. Taken together, the DOT
      genes include both components and regulators of silent chromatin.

PMID- 9755196
TI  - Tetrahymena mutants with short telomeres.
AB  - Telomere length is dynamic in many organisms. Genetic screens that identify
      mutants with altered telomere lengths are essential if we are to understand how
      telomere length is regulated in vivo. In Tetrahymena thermophila, telomeres
      become long at 30 degrees, and growth rate slows. A slow-growing culture with
      long telomeres is often overgrown by a variant cell type with short telomeres and
      a rapid-doubling rate. Here we show that this variant cell type with short
      telomeres is in fact a mutant with a genetic defect in telomere length
      regulation. One of these telomere growth inhibited forever (tgi) mutants was
      heterozygous for a telomerase RNA mutation, and this mutant telomerase RNA caused
      telomere shortening when overexpressed in wild-type cells. Several other tgi
      mutants were also likely to be heterozygous at their mutant loci, since they
      reverted to wild type when selective pressure for short telomeres was removed.
      These results illustrate that telomere length can regulate growth rate in
      Tetrahymena and that this phenomenon can be exploited to identify genes involved
      in telomere length regulation.

PMID- 9755197
TI  - The male-determining activity on the Y chromosome of the housefly (Musca
      domestica L.) consists of separable elements.
AB  - In the common housefly, the presence or absence of a male-determining factor, M,
      is responsible for sex determination. In different strains, M has been found on
      the Y, on the X, or on any of the five autosomes. By analyzing a Y-autosomal
      translocation and a ring-shaped, truncated Y chromosome, we could show that M on
      the Y consists of at least two regions with M activity: One of them can be
      assigned to the short arm of the Y chromosome (MYS), which is largely C-banding
      negative, the other region lies on the C-banding positive long arm of the Y,
      including the centromeric part (MYL). Each region alone behaves as a hypomorphic
      M factor, causing many carriers to develop as intersexes of the mosaic type
      instead of as males. When introduced into the female germ line by transplantation
      of progenitor germ cells (pole cells), the MYS shows an almost complete maternal
      effect that predetermines 96% of the genotypic female (NoM) animals to develop as
      males. In contrast, the MYL has largely lost its maternal effect, and most of the
      NoM animals develop as females. Increasing the amount of product made by either
      of the two hypomorphic M factors (by combining the MYS and MYL or two MYS) leads
      to complete male development in almost every case. We thus assume that the Y
      chromosome carries at least two copies of M, and that these are functionally
      equivalent.

PMID- 9755198
TI  - Functional analysis of the fibrinogen-related scabrous gene from Drosophila
      melanogaster identifies potential effector and stimulatory protein domains.
AB  - The scabrous (sca) gene encodes a secreted dimeric glycoprotein with putative
      coiled-coil domains N-terminally and a C-terminal region related to the blood
      clot protein fibrinogen. Homozygous sca mutants have extra bristle organs and
      rough eyes. We describe a GAL4-based expression system for testing rescue of the
      sca mutant phenotype by altered SCA proteins and for misexpression. We find that
      deletion of the fibrinogen-related domain (FReD) greatly decreases SCA function,
      confirming the importance of this conserved region. SCA function could not be
      restored by FReDs from human fibrinogen chain genes. However, proteins lacking
      any FReD still showed some function in both rescue and misexpression experiments,
      suggesting that putative effector-binding regions lie outside this domain.
      Consistent with this, proteins expressing only the FReD had no rescuing activity
      but were recessive negative; i.e., they enhanced the phenotype of sca mutations
      but had no phenotype in the presence of a wild-type sca allele. This suggests
      that the FReD contributes to SCA function by binding to other components of the
      bristle determination pathway, increasing the activity of the linked N-terminal
      region.

PMID- 9755199
TI  - Expression and properties of wild-type and mutant forms of the Drosophila sex
      comb on midleg (SCM) repressor protein.
AB  - The Sex comb on midleg (Scm) gene encodes a transcriptional repressor of the
      Polycomb group (PcG). Here we show that SCM protein is nuclear and that its
      expression is widespread during fly development. SCM protein contains a C
      terminal domain, termed the SPM domain, which mediates protein-protein
      interactions. The biochemical function of another domain consisting of two 100
      amino-acid-long repeats, termed "mbt" repeats, is unknown. We have determined the
      molecular lesions of nine Scm mutant alleles, which identify functional
      requirements for specific domains. The Scm alleles were tested for genetic
      interactions with mutations in other PcG genes. Intriguingly, three hypomorphic
      Scm mutations, which map within an mbt repeat, interact with PcG mutations more
      strongly than do Scm null alleles. The strongest interactions produce partial
      synthetic lethality that affects doubly heterozygous females more severely than
      males. We show that mbt repeat alleles produce stable SCM proteins that associate
      with normal sites in polytene chromosomes. We also analyzed progeny from Scm
      mutant germline clones to compare the effects of an mbt repeat mutation during
      embryonic vs. pupal development. We suggest that the mbt repeat alleles produce
      altered SCM proteins that incorporate into and impair function of PcG protein
      complexes.

PMID- 9755200
TI  - P-Element insertion at the polyhomeotic gene leads to formation of a novel
      chimeric protein that negatively regulates yellow gene expression in P-element
      induced alleles of Drosophila melanogaster.
AB  - Polyhomeotic is a member of the Polycomb group (Pc-G) of homeotic repressors. The
      proteins encoded by the Pc-G genes form repressive complexes on the polycomb
      group response element sites. The phP1 mutation was induced by insertion of a 1.2
      kb P element into the 5' transcribed nontranslated region of the proximal
      polyhomeotic gene. The phP1 allele confers no mutant phenotype, but represses
      transcription of P-element-induced alleles at the yellow locus. The phP1 allele
      encodes a chimeric P-PH protein, consisting of the DNA-binding domain of the P
      element and the PH protein lacking 12 amino-terminal amino acids. The P-PH,
      Polycomb (PC), and Posterior sex combs (PSC) proteins were immunohistochemically
      detected on polytene chromosomes in the regions of P-element insertions.

PMID- 9755201
TI  - Modulation of MSL1 abundance in female Drosophila contributes to the sex
      specificity of dosage compensation.
AB  - Dosage compensation in Drosophila is the mechanism by which X-linked gene
      expression is made equal in males and females. Proper regulation of this process
      is critical to the survival of both sexes. Males must turn the male-specific
      lethal (msl)-mediated pathway of dosage compensation on and females must keep it
      off. The msl2 gene is the primary target of negative regulation in females.
      Preventing production of MSL2 protein is sufficient to prevent dosage
      compensation; however, ectopic expression of MSL2 protein in females is not
      sufficient to induce an insurmountable level of dosage compensation, suggesting
      that an additional component is limiting in females. A candidate for this
      limiting factor is MSL1, because the amount of MSL1 protein in females is reduced
      compared to males. We have identified two levels of negative regulation of msl1
      in females. The predominant regulation is at the level of protein stability,
      while a second regulatory mechanism functions at the level of protein synthesis.
      Overcoming these control mechanisms by overexpressing both MSL1 and MSL2 in
      females results in 100% female-specific lethality.

PMID- 9755202
TI  - LUSH odorant-binding protein mediates chemosensory responses to alcohols in
      Drosophila melanogaster.
AB  - The molecular mechanisms mediating chemosensory discrimination in insects are
      unknown. Using the enhancer trapping approach, we identified a new Drosophila
      mutant, lush, with odorant-specific defects in olfactory behavior. lush mutant
      flies are abnormally attracted to high concentrations of ethanol, propanol, and
      butanol but have normal chemosensory responses to other odorants. We show that
      wild-type flies have an active olfactory avoidance mechanism to prevent
      attraction to concentrated alcohol, and this response is defective in lush
      mutants. This suggests that the defective olfactory behavior associated with the
      lush mutation may result from a specific defect in chemoavoidance. lush mutants
      have a 3-kb deletion that produces a null allele of a new member of the
      invertebrate odorant-binding protein family, LUSH. LUSH is normally expressed
      exclusively in a subset of trichoid chemosensory sensilla located on the ventral
      lateral surface of the third antennal segment. LUSH is secreted from nonneuronal
      support cells into the sensillum lymph that bathes the olfactory neurons within
      these sensilla. Reintroduction of a cloned wild-type copy of lush into the mutant
      background completely restores wild-type olfactory behavior, demonstrating that
      this odorant-binding protein is required in a subset of sensilla for normal
      chemosensory behavior to a subset of odorants. These findings provide direct
      evidence that odorant-binding proteins are required for normal chemosensory
      behavior in Drosophila and may partially determine the chemical specificity of
      olfactory neurons in vivo.

PMID- 9755203
TI  - Evidence for 3' untranslated region-dependent autoregulation of the Drosophila
      gene encoding the neuronal nuclear RNA-binding protein ELAV.
AB  - The Drosophila locus embryonic lethal abnormal visual system (elav) encodes a
      nuclear RNA-binding protein essential for normal neuronal differentiation and
      maintenance of neurons. ELAV is thought to play its role by binding to RNAs
      produced by other genes necessary for neuronal differentiation and consequently
      to affect their metabolism by an as yet unknown mechanism. ELAV structural
      homologues have been identified in a wide range of organisms, including humans,
      indicating an important conserved role for the protein. Analysis of elav germline
      transformants presented here shows that one copy of elav minigenes lacking a
      complete 3' untranslated region (3' UTR) rescues null mutations at elav, but that
      two copies are lethal. Additional in vivo experiments demonstrate that elav
      expression is regulated through the 3' UTR of the gene and indicate that this
      level of regulation is dependent upon ELAV itself. Because ELAV is an RNA-binding
      protein, the simplest model to account for these findings is that ELAV binds to
      the 3' UTR of its own RNA to autoregulate its expression. I discuss the
      implications of these results for normal elav function.

PMID- 9755204
TI  - Y-Linked male sterile mutations induced by P element in Drosophila melanogaster.
AB  - The Y chromosome in Drosophila melanogaster is composed of highly repetitive
      sequences and is essential only in the male germ line. We employed P-element
      insertional mutagenesis to induce male sterile mutations in the Y chromosome. By
      using a combination of two modifiers of position effect variegation, adding an
      extra Y chromosome and increasing temperature, we isolated 61 P(ry+) elements in
      the Y chromosome. Six of these Y-linked insertions (approximately 10%) induced
      male sterile mutations that are mapped to two genes on the long and one on the
      short arms of the Y chromosome. These mutations are revertible to the wild type
      in a cell-autonomous and germ-line-dependent manner, consistent with previously
      defined Y-linked gene functions. Phenotypes associated with these P-induced
      mutations are similar to those resulting from deletions of the Y chromosome
      regions corresponding to the male fertility genes. Three alleles of the kl-3 gene
      on the Y long arm result in loss of the axonemal outer dynein arms in the
      spermatid tail, while three ks-2 alleles on the Y short arm induce defects at
      early postmeiotic stages. The recovery of the ms(Y) mutations induced by single P
      element insertions will facilitate our effort to understand the structural and
      functional properties of the Y chromosome.

PMID- 9755205
TI  - Hidden effects of X chromosome introgressions on spermatogenesis in Drosophila
      simulans x D. mauritiana hybrids unveiled by interactions among minor genetic
      factors.
AB  - One of the most frequent outcomes of interspecific hybridizations in Drosophila
      is hybrid male sterility. Genetic dissection of this reproductive barrier has
      revealed that the number of responsible factors is very high and that these
      factors are frequently engaged in complex epistatic interactions. Traditionally,
      research strategies have been based on contrasting introgressions of chromosome
      segments that produce male sterility with those that allow fertility. Few studies
      have investigated the phenotypes associated with the boundary between fertility
      and sterility. In this study, we cointrogressed three different X chromosome
      segments from Drosophila mauritiana into D. simulans. Hybrid males with these
      three segments are usually fertile, by conventional fertility assays. However,
      their spermatogenesis shows a significant slowdown, most manifest at lower
      temperatures. Each of the three introgressed segments retards the arrival of
      sperm to the seminal vesicles. Other small disturbances in spermatogenesis are
      evident, which altogether lead to an overall reduction in the amount of motile
      sperm in their seminal vesicles. These results suggest that a delay in the timing
      of spermatogenesis, which might be brought about by the cumulative action of many
      different factors of minor segment, may be the primary cause of hybrid male
      sterility.

PMID- 9755206
TI  - Quantitative genetic analysis of copia retrotransposon activity in inbred
      Drosophila melanogaster lines.
AB  - The rates of transcription and transposition of retrotransposons vary between
      lines of Drosophila melanogaster. We have studied the genetics of differences in
      copia retrotransposon activity by quantitative trait loci (QTL) mapping. Ninety
      eight recombinant inbred lines were constructed from two parental lines
      exhibiting a 10-fold difference in copia transcript level and a 100-fold
      difference in transposition rate. The lines were scored for 126 molecular
      markers, copia transcript level, and rate of copia transposition. Transcript
      level correlated with copia copy number, and the difference in copia copy number
      between parental lines accounted for 45.1% of copia transcript-level difference.
      Most of the remaining difference was accounted for by two transcript-level QTL
      mapping to cytological positions 27B-30D and 50F-57C on the second chromosome,
      which accounted for 11.5 and 30.4%, respectively. copia transposition rate was
      controlled by interacting QTL mapping to the region 27B-48D on the second and 61A
      65A and 97D-100A on the third chromosome. The genes controlling copia transcript
      level are thus not necessarily those involved in controlling copia transposition
      rate. Segregation of modifying genes, rather than mutations, might explain the
      variability in copia retrotransposon activity between lines.

PMID- 9755207
TI  - The correlation between synonymous and nonsynonymous substitutions in Drosophila:
      mutation, selection or relaxed constraints?
AB  - Codon usage bias, the preferential use of particular codons within each codon
      family, is characteristic of synonymous base composition in many species,
      including Drosophila, yeast, and many bacteria. Preferential usage of particular
      codons in these species is maintained by natural selection acting largely at the
      level of translation. In Drosophila, as in bacteria, the rate of synonymous
      substitution per site is negatively correlated with the degree of codon usage
      bias, indicating stronger selection on codon usage in genes with high codon bias
      than in genes with low codon bias. Surprisingly, in these organisms, as well as
      in mammals, the rate of synonymous substitution is also positively correlated
      with the rate of nonsynonymous substitution. To investigate this correlation, we
      carried out a phylogenetic analysis of substitutions in 22 genes between two
      species of Drosophila, Drosophila pseudoobscura and D. subobscura, in codons that
      differ by one replacement and one synonymous change. We provide evidence for a
      relative excess of double substitutions in the same species lineage that cannot
      be explained by the simultaneous mutation of two adjacent bases. The synonymous
      changes in these codons also cannot be explained by a shift to a more preferred
      codon following a replacement substitution. We, therefore, interpret the excess
      of double codon substitutions within a lineage as being the result of relaxed
      constraints on both kinds of substitutions in particular codons.

PMID- 9755208
TI  - Genetic variation and differentiation at microsatellite loci in Drosophila
      simulans. Evidence for founder effects in new world populations.
AB  - Drosophila simulans isofemale lines from Africa, South America, and two locations
      in North America were surveyed for variation at 16 microsatellite loci on the X,
      second, and third chromosomes, and 18 microsatellites, which are unmapped. D.
      simulans is thought to have colonized New World habitats only relatively recently
      (within the last few hundred years). Consistent with a founder effect occurring
      as colonizers moved into these New World habitats, we find less microsatellite
      variability in North and South American D. simulans populations than for an
      African population. Population subdivision as measured at microsatellites is
      moderate when averaged across all loci (FST = 0.136), but contrasts sharply with
      previous studies of allozyme variation, which have showed significantly less
      differentiation in D. simulans than in D. melanogaster. There are substantially
      fewer private alleles observed in New World populations of D. simulans than seen
      in a similar survey of D. melanogaster. In addition to possible differences in
      population size during their evolutionary histories, varying colonization
      histories or other demographic events may be necessary to explain discrepancies
      in the patterns of variation observed at various genetic markers between these
      closely related species.

PMID- 9755210
TI  - Multiple origins of cytologically identical chromosome inversions in the
      Anopheles gambiae complex.
AB  - For more than 60 years, evolutionary cytogeneticists have been using naturally
      occurring chromosomal inversions to infer phylogenetic histories, especially in
      insects with polytene chromosomes. The validity of this method is predicated on
      the assumption that inversions arise only once in the history of a lineage, so
      that sharing a particular inversion implies shared common ancestry. This
      assumption of monophyly has been generally validated by independent data. We
      present the first clear evidence that naturally occurring inversions, identical
      at the level of light microscopic examination of polytene chromosomes, may not
      always be monophyletic. The evidence comes from DNA sequence analyses of regions
      within or very near the breakpoints of an inversion called the 2La that is found
      in the Anopheles gambiae complex. Two species, A. merus and A. arabiensis, which
      are fixed for the "same" inversion, do not cluster with each other in a
      phylogenetic analysis of the DNA sequences within the 2La. Rather, A. merus 2La
      is most closely related to strains of A. gambiae homozygous for the 2L+. A.
      gambiae and A. merus are sister taxa, the immediate ancestor was evidently
      homozygous 2L+, and A. merus became fixed for an inversion cytologically
      identical to that in A. arabiensis. A. gambiae is polymorphic for 2La/2L+, and
      the 2La in this species is nearly identical at the DNA level to that in A.
      arabiensis, consistent with the growing evidence that introgression has or is
      occurring between these two most important vectors of malaria in the world. The
      parallel evolution of the "same" inversion may be promoted by the presence of
      selectively important genes within the breakpoints.

PMID- 9755211
TI  - Deletion mapping of the head tilt (het) gene in mice: a vestibular mutation
      causing specific absence of otoliths.
AB  - Head tilt (het) is a recessive mutation in mice causing vestibular dysfunction.
      Homozygotes display abnormal responses to position change and linear acceleration
      and cannot swim. However, they are not deaf. het was mapped to the proximal
      region of mouse chromosome 17, near the T locus. Here we report anatomical
      characterization of het mutants and high resolution mapping using a set of
      chromosome deletions. The defect in het mutants is limited to the utricle and
      saccule of the inner ear, which completely lack otoliths. The unique specificity
      of the het mutation provides an opportunity to better understand the development
      of the vestibular system. Complementation analyses with a collection of embryonic
      stem (ES)- and germ cell-induced deletions localized het to an interval near the
      centromere of chromosome 17 that was indivisible by recombination mapping. This
      approach demonstrates the utility of chromosome deletions as reagents for mapping
      and characterizing mutations, particularly in situations where recombinational
      mapping is inadequate.

PMID- 9755209
TI  - A screen to identify Drosophila genes required for integrin-mediated adhesion.
AB  - Drosophila integrins have essential adhesive roles during development, including
      adhesion between the two wing surfaces. Most position-specific integrin mutations
      cause lethality, and clones of homozygous mutant cells in the wing do not adhere
      to the apposing surface, causing blisters. We have used FLP-FRT induced mitotic
      recombination to generate clones of randomly induced mutations in the F1
      generation and screened for mutations that cause wing blisters. This phenotype is
      highly selective, since only 14 lethal complementation groups were identified in
      screens of the five major chromosome arms. Of the loci identified, 3 are PS
      integrin genes, 2 are blistered and bloated, and the remaining 9 appear to be
      newly characterized loci. All 11 nonintegrin loci are required on both sides of
      the wing, in contrast to integrin alpha subunit genes. Mutations in 8 loci only
      disrupt adhesion in the wing, similar to integrin mutations, while mutations in
      the 3 other loci cause additional wing defects. Mutations in 4 loci, like the
      strongest integrin mutations, cause a "tail-up" embryonic lethal phenotype, and
      mutant alleles of 1 of these loci strongly enhance an integrin mutation. Thus
      several of these loci are good candidates for genes encoding cytoplasmic proteins
      required for integrin function.

PMID- 9755212
TI  - Molecular evolution of an imprinted gene: repeatability of patterns of evolution
      within the mammalian insulin-like growth factor type II receptor.
AB  - The repeatability of patterns of variation in Ka/Ks and Ks is expected if such
      patterns are the result of deterministic forces. We have contrasted the molecular
      evolution of the mammalian insulin-like growth factor type II receptor (Igf2r) in
      the mouse-rat comparison with that in the human-cow comparison. In so doing, we
      investigate explanations for both the evolution of genomic imprinting and for Ks
      variation (and hence putatively for mutation rate evolution). Previous analysis
      of Igf2r, in the mouse-rat comparison, found Ka/Ks patterns that were suggested
      to be contrary to those expected under the conflict theory of imprinting. We find
      that Ka/Ks variation is repeatable and hence confirm these patterns. However, we
      also find that the molecular evolution of Igf2r signal sequences suggests that
      positive selection, and hence conflict, may be affecting this region. The
      variation in Ks across Igf2r is also repeatable. To the best of our knowledge
      this is the first demonstration of such repeatability. We consider three
      explanations for the variation in Ks across the gene: (1) that it is the result
      of mutational biases, (2) that it is the result of selection on the mutation
      rate, and (3) that it is the product of selection on codon usage. Explanations 2
      and 3 predict a Ka-Ks correlation, which is not found. Explanation 3 also
      predicts a negative correlation between codon bias and Ks, which is also not
      found. However, in support of explanation 1 we do find that in rodents the rate
      of silent C --> T mutations at CpG sites does covary with Ks, suggesting that
      methylation-induced mutational patterns can explain some of the variation in Ks.
      We find evidence to suggest that this CpG effect is due to both variation in CpG
      density, and to variation in the frequency with which CpGs mutate. Interestingly,
      however, a GC4 analysis shows no covariance with Ks, suggesting that to eliminate
      methyl-associated effects CpG rates themselves must be analyzed. These results
      suggest that, in contrast to previous studies of intragenic variation, Ks
      patterns are not simply caused by the same forces responsible for Ka/Ks
      correlations.

PMID- 9755214
TI  - Speciation and domestication in maize and its wild relatives: evidence from the
      globulin-1 gene.
AB  - The grass genus Zea contains the domesticate maize and several wild taxa
      indigenous to Central and South America. Here we study the genetic consequences
      of speciation and domestication in this group by sampling DNA sequences from four
      taxa-maize (Zea mays ssp. mays), its wild progenitor (Z. mays ssp. parviglumis),
      a more distant species within the genus (Z. luxurians), and a representative of
      the sister genus (Tripsacum dactyloides). We sampled a total of 26 sequences from
      the glb1 locus, which encodes a nonessential seed storage protein. Within the Zea
      taxa sampled, the progenitor to maize contains the most sequence diversity. Maize
      contains 60% of the level of genetic diversity of its progenitor, and Z.
      luxurians contains even less diversity (32% of the level of diversity of Z. mays
      ssp. parviglumis). Sequence variation within the glb1 locus is consistent with
      neutral evolution in all four taxa. The glb1 data were combined with adh1 data
      from a previous study to make inferences about the population genetic histories
      of these taxa. Comparisons of sequence data between the two morphologically
      similar wild Zea taxa indicate that the species diverged approximately 700, 000
      years ago from a common ancestor of intermediate size to their present
      populations. Conversely, the domestication of maize was a recent event that could
      have been based on a very small number of founding individuals. Maize retained a
      substantial proportion of the genetic variation of its progenitor through this
      founder event, but diverged rapidly in morphology.

PMID- 9755213
TI  - Genetic variation and phylogeography of central Asian and other house mice,
      including a major new mitochondrial lineage in Yemen.
AB  - The mitochondrial DNA (mtDNA) control region and flanking tRNAs were sequenced
      from 76 mice collected at 60 localities extending from Egypt through Turkey,
      Yemen, Iran, Afghanistan, Pakistan, and Nepal to eastern Asia. Segments of the Y
      chromosome and of a processed p53 pseudogene (Psip53) were amplified from many of
      these mice and from others collected elsewhere in Eurasia and North Africa. The
      251 mtDNA types, including 54 new ones reported here, now identified from
      commensal house mice (Mus musculus group) by sequencing this segment can be
      organized into four major lineages-domesticus, musculus, castaneus, and a new
      lineage found in Yemen. Evolutionary tree analysis suggested the domesticus
      mtDNAs as the sister group to the other three commensal mtDNA lineages and the
      Yemeni mtDNAs as the next oldest lineage. Using this tree and the phylogeographic
      approach, we derived a new model for the origin and radiation of commensal house
      mice whose main features are an origin in west-central Asia (within the present
      day range of M. domesticus) and the sequential spreading of mice first to the
      southern Arabian Peninsula, thence eastward and northward into south-central
      Asia, and later from south-central Asia to north-central Asia (and thence into
      most of northern Eurasia) and to southeastern Asia. Y chromosomes with and
      without an 18-bp deletion in the Zfy-2 gene were detected among mice from Iran
      and Afghanistan, while only undeleted Ys were found in Turkey, Yemen, Pakistan,
      and Nepal. Polymorphism for the presence of a Psip53 was observed in Georgia,
      Iran, Turkmenistan, Afghanistan, and Pakistan. Sequencing of a 128-bp Psip53
      segment from 79 commensal mice revealed 12 variable sites and implicated >/=14
      alleles. The allele that appeared to be phylogenetically ancestral was
      widespread, and the greatest diversity was observed in Turkey, Afghanistan,
      Pakistan, and Nepal. Two mice provided evidence for a second Psip53 locus in some
      commensal populations.

PMID- 9755215
TI  - Organization and expression of the mitochondrial genome in the Nicotiana
      sylvestris CMSII mutant.
AB  - Previous analyses suggested that the Nicotiana sylvestris CMSII mutant carried a
      large deletion in its mitochondrial genome. Here, we show by cosmid mapping that
      the deletion is 60 kb in length and contains several mitochondrial genes or ORFs,
      including the complex I nad7 gene. However, due to the presence of large
      duplications in the progenitor mitochondrial genome, the only unique gene that
      appears to be deleted is nad7. RNA gel blot data confirm the absence of nad7
      expression, strongly suggesting that the molecular basis for the CMSII abnormal
      phenotype, poor growth and male sterility, is the altered complex I structure.
      The CMSII mitochondrial genome appears to consist essentially of one of two
      subgenomes resulting from recombination between direct short repeats. In the
      progenitor mitochondrial genome both recombination products are detected by PCR
      and, reciprocally, the parental fragments are detected at the substoichiometric
      level in the mutant. The CMSII mtDNA organization has been maintained through six
      sexual generations.

PMID- 9755216
TI  - A high-resolution linkage map of the citrus tristeza virus resistance gene region
      in Poncirus trifoliata (L.) Raf.
AB  - Resistance to citrus tristeza virus (CTV) was evaluated in 554 progeny of 10
      populations derived from Poncirus trifoliata. A dominant gene (Ctv) controlled
      CTV resistance in P. trifoliata. Twenty-one dominant PCR-based DNA markers were
      identified as linked to Ctv by bulked segregant analysis. Of the 11 closest
      markers to Ctv, only 2 segregated in all populations. Ten of these markers were
      cloned and sequenced, and codominant RFLP markers were developed. Seven RFLP
      markers were then evaluated in 10 populations. Marker orders were consistent in
      all linkage maps based on data of single populations or on combined data of
      populations with similar segregation patterns. In a consensus map, the six
      closest marker loci spanned 5.3 cM of the Ctv region. Z16 cosegregated with Ctv.
      C19 and AD08 flanked Ctv at distances of 0.5 and 0.8 cM, respectively. These 3
      markers were present as single copies in the Poncirus genome, and could be used
      directly for bacterial artificial chromosome library screening to initiate a walk
      toward Ctv. BLAST searches of the GenBank database revealed high sequence
      similarities between 2 markers and known plant disease resistance genes,
      indicating that a resistance gene cluster exists in the Ctv region in P.
      trifoliata.

PMID- 9755217
TI  - Epigenetic allelic states of a maize transcriptional regulatory locus exhibit
      overdominant gene action.
AB  - Using alleles of the maize purple plant locus (pl), which encodes a
      transcriptional regulator of anthocyanin pigment synthesis, we describe a case of
      single-locus heterosis, or overdominance, where the heterozygote displays a
      phenotype that is greater than either homozygote. The Pl-Rhoades (Pl-Rh) allele
      is subject to epigenetic changes in gene expression, resulting in quantitatively
      distinct expression states. Allelic states with low-expression levels, designated
      Pl'-mahogany (Pl'-mah), are dominant to the high-expression state of Pl-Rh. Pl'
      mah states retain low-expression levels in subsequent generations when homozygous
      or heterozygous with Pl-Rh. However, Pl'-mah alleles frequently exhibit higher
      expression levels when heterozygous with other pl alleles; illustrating an
      overdominant allelic relationship. Higher expression levels are also observed
      when Pl'-mah is hemizygous. These results suggest that persistent allelic
      interactions between Pl'-mah and Pl-Rh are required to maintain the low
      expression state and that other pl alleles are missing sequences required for
      this interaction. The Pl-Rh state can be sexually transmitted from Pl'-mah/pl
      heterozygotes, but not from Pl'-mah hemizygotes, suggesting that fixation of the
      high-expression state may involve synapsis. The existence of such allele
      dependent regulatory mechanisms implicates a novel importance of allele
      polymorphisms in the genesis and maintenance of genetic variation.

PMID- 9755218
TI  - Identification of trait-improving quantitative trait loci alleles from a wild
      rice relative, Oryza rufipogon.
AB  - Wild species are valued as a unique source of genetic variation, but they have
      rarely been used for the genetic improvement of quantitative traits. To identify
      trait-improving quantitative trait loci (QTL) alleles from exotic species, an
      accession of Oryza rufipogon, a relative of cultivated rice, was chosen on the
      basis of a genetic diversity study. An interspecific BC2 testcross population
      (V20A/O. rufipogon//V20B///V20B////Ce64) consisting of 300 families was evaluated
      for 12 agronomically important quantitative traits. The O. rufipogon accession
      was phenotypically inferior for all 12 traits. However, transgressive segregants
      that outperformed the original elite hybrid variety, V20A/Ce64, were observed for
      all traits examined. A set of 122 RFLP and microsatellite markers was used to
      identify QTL. A total of 68 significant QTL were identified, and of these, 35
      (51%) had beneficial alleles derived from the phenotypically inferior O.
      rufipogon parent. Nineteen (54%) of these beneficial QTL alleles were free of
      deleterious effects on other characters. O. rufipogon alleles at two QTL on
      chromosomes 1 and 2 were associated with an 18 and 17% increase in grain yield
      per plant, respectively, without delaying maturity or increasing plant height.
      This discovery suggests that the innovative use of molecular maps and markers can
      alter the way geneticists utilize wild and exotic germplasm.

PMID- 9755220
TI  - Analysis of population structure in autotetraploid species.
AB  - Population structure parameters commonly used for diploid species are reexamined
      for the particular case of tetrasomic inheritance (autotetraploid species).
      Recurrence equations that describe the evolution of identity probabilities for
      neutral genes in an "island model" of population structure are derived assuming
      tetrasomic inheritance. The expected equilibrium value of FST is computed. In
      contrast to diploids, the correlation of genes between individuals within
      populations with respect to genes between populations (FST) may vary among loci
      due to the particular segregation patterns expected under tetrasomic inheritance
      and is consequently inappropriate for estimating demographic parameters in such
      populations. We thus define a new parameter (rho) and derive its relationship
      with Nm. This relationship is shown to be independent from both the selfing rate
      and the proportion of double reduction. Finally, the statistical procedure
      required to evaluate these parameters using data on gene frequencies distribution
      among autotetraploid populations is developed.

PMID- 9755219
TI  - Should we expect substitution rate to depend on population size?
AB  - The rate of nucleotide substitution is generally believed to be a decreasing
      function of effective population size, at least for nonsynonymous substitutions.
      This view was originally based on consideration of slightly deleterious mutations
      with a fixed distribution of selection coefficients. A realistic model must
      include the occurrence and fixation of some advantageous mutations that
      compensate for the loss of fitness due to deleterious substitutions. Some such
      models, such as so-called "fixed" models, also predict a population size effect
      on substitution rate. An alternative model, presented here, predicts the near
      absence of a population size effect on substitution rate. This model is based on
      concave log-fitness functions and a fixed distribution of mutational effects on
      the selectively important trait. Simulations of an instance of the model confirm
      the approximate insensitivity of the substitution rate to population size.
      Although much experimental evidence has been claimed to support the existence of
      a population size effect, the body of evidence as a whole is equivocal, and much
      of the evidence that is supposed to demonstrate such an effect would also suggest
      that it is very small. Perhaps the proposed model applies well to some genes and
      not so well to others, and genes therefore vary with regard to the population
      size effect.

PMID- 9755221
TI  - A nonparametric bootstrap method for testing close linkage vs. pleiotropy of
      coincident quantitative trait loci.
AB  - A novel method using the nonparametric bootstrap is proposed for testing whether
      a quantitative trait locus (QTL) at one chromosomal position could explain
      effects on two separate traits. If the single-QTL hypothesis is accepted,
      pleiotropy could explain the effect on two traits. If it is rejected, then the
      effects on two traits are due to linked QTLs. The method can be used in
      conjunction with several QTL mapping methods as long as they provide a
      straightforward estimate of the number of QTLs detectable from the data set. A
      selection step was introduced in the bootstrap procedure to reduce the
      conservativeness of the test of close linkage vs. pleiotropy, so that the
      erroneous rejection of the null hypothesis of pleiotropy only happens at a
      frequency equal to the nominal type I error risk specified by the user. The
      approach was assessed using computer simulations and proved to be relatively
      unbiased and robust over the range of genetic situations tested. An example of
      its application on a real data set from a saline stress experiment performed on a
      recombinant population of wheat (Triticum aestivum L. ) doubled haploid lines is
      also provided.

PMID- 9755222
TI  - Characterization of deleterious mutations in outcrossing populations.
AB  - Deng and Lynch recently proposed estimating the rate and effects of deleterious
      genomic mutations from changes in the mean and genetic variance of fitness upon
      selfing/outcrossing in outcrossing/highly selfing populations. The utility of our
      original estimation approach is limited in outcrossing populations, since selfing
      may not always be feasible. Here we extend the approach to any form of inbreeding
      in outcrossing populations. By simulations, the statistical properties of the
      estimation under a common form of inbreeding (sib mating) are investigated under
      a range of biologically plausible situations. The efficiencies of different
      degrees of inbreeding and two different experimental designs of estimation are
      also investigated. We found that estimation using the total genetic variation in
      the inbred generation is generally more efficient than employing the genetic
      variation among the mean of inbred families, and that higher degree of inbreeding
      employed in experiments yields higher power for estimation. The simulation
      results of the magnitude and direction of estimation bias under variable or
      epistatic mutation effects may provide a basis for accurate inferences of
      deleterious mutations. Simulations accounting for environmental variance of
      fitness suggest that, under full-sib mating, our extension can achieve reasonably
      well an estimation with sample sizes of only approximately 2000-3000.

PMID- 9755223
TI  - Dietary fat and alcoholic liver disease.

PMID- 9755224
TI  - Cryptosporidium parvum is cytopathic for cultured human biliary epithelia via an
      apoptotic mechanism.
AB  - While the clinical features of sclerosing cholangitis secondary to opportunistic
      infections of the biliary tree in patients with acquired immunodeficiency
      syndrome (AIDS) are well known, the mechanisms by which microbial pathogens such
      as Cryptosporidium parvum associated with this syndrome actually cause disease
      are obscure. We established an in vitro model of biliary cryptosporidiosis
      employing a human biliary epithelial cell line. Using morphological and
      biochemical techniques, we examined the interaction of C. parvum with cultured
      human cholangiocytes. When the apical plasma membrane of polarized, confluent
      monolayers of human biliary epithelial cells was exposed to C. parvum oocysts
      that had been excysted in vitro, sporozoites attached to and invaded the cells in
      a time-, dose-, temperature-, and pH-dependent manner. The infectious process was
      both plasma membrane domain- and cell-specific, because no attachment or invasion
      occurred when the basolateral membrane of cholangiocytes was exposed to the
      parasite, or when a human hepatocyte cell line (HepG2) was used. Time-lapse video
      microscopy and scanning electron microscopy (SEM) showed that sporozoite
      attachment was rapid, involved extensive cholangiocyte membrane ruffling, and
      culminated in parasite penetration into a tight-fitting vacuole formed by
      invagination of the plasma membrane similar to those found in naturally occurring
      infection in vivo. Transmission electron microscopy (TEM) showed that C. parvum
      organisms formed parasitophorus vacuoles and were able to undergo a complete
      reproductive cycle, forming both asexual and sexual reproductive stages.
      Unexpectedly, direct cytopathic effects were noted in infected monolayers, with
      widespread programmed cell death (i.e., apoptosis) of biliary epithelial cells as
      assessed both morphologically and biochemically beginning within hours after
      exposure to the organism. The novel finding of specific cytopathic invasion of
      biliary epithelia by C. parvum may be relevant to the pathogenesis and possible
      therapy of the secondary sclerosing cholangitis seen in AIDS patients with
      biliary cryptosporidiosis.

PMID- 9755225
TI  - Purinergic regulation of acid/base transport in human and rat biliary epithelial
      cell lines.
AB  - Biliary epithelial cells (cholangiocytes) are responsible for rapid regulation of
      bile volume and alkalinity. Secretin and other hormones raising intracellular
      cyclic adenosine monophosphate (cAMP) concentrations promote biliary HCO3
      secretion by stimulating apical Cl- channels and Cl-/HCO3- exchange (AE2).
      Cholangiocyte ion transport may also be stimulated by locally acting mediators;
      for example, adenosine 5'-triphosphate (ATP), a secretagogue that can be released
      into the bile by hepatocytes and cholangiocytes, activates Cl- conductances and
      Na+/H+ exchange (NHE) in cholangiocyte cell lines. To further explore the role of
      extracellular ATP in the paracrine regulation of carrier mechanisms regulating
      cholangiocyte H+/HCO3- secretion, we investigated the effects of nucleotides on
      intracellular pH regulation (measured by microfluorimetry with 2'7'-bis(2
      carboxyethyl)-5,6,carboxyfluorescein [BCECF]) in human (MZ-ChA-1) and rat (NRC-1)
      cholangiocyte cell lines. In MZ-ChA-1 cells, 10 mol/L ATP, uridine 5'
      triphosphate (UTP), and ATPgammas significantly increased NHE activity. The
      pharmacological profile of agonists was consistent with that anticipated for
      receptors of the P2Y2 class. ATP did not increase AE2 activity, but, when given
      to cells pretreated with agents raising intracellular cAMP, had a synergistic
      stimulatory effect that was inhibited by amiloride. To assess the polarity of
      purinergic receptors, monolayers of NRC-1 cells were exposed to apical or
      basolateral nucleotides. Apical administration of purinergic agonists, but not
      adenosine, increased basolateral NHE activity (ATPgammaS > UTP > ATP).
      Basolateral administration of purinergic agonists induced a weaker activation of
      NHE, which was instead strongly stimulated by adenosine and by adenosine receptor
      agonists (NECA = R-PIA = S-PIA). In conclusion, this study demonstrates that,
      consistent with the proposed role for biliary ATP in paracrine and autocrine
      control of cholangiocyte ion secretion, extracellular ATP stimulates
      cholangiocyte basolateral NHE activity through P2Y2 receptors that are
      predominantly expressed at the apical cell membrane.

PMID- 9755226
TI  - Risk of liver and other types of cancer in patients with cirrhosis: a nationwide
      cohort study in Denmark.
AB  - Cancer risk in patients with cirrhosis could be modified by factors such as
      changes in hormonal levels, impaired metabolism of carcinogens, or alteration of
      immunological status. We investigated the risk of liver and various forms of
      cancer in patients with cirrhosis in a follow-up study. We identified 11,605 1
      year survivors of cirrhosis from the files of the Danish National Registry of
      Patients (NRP) from 1977 to 1989. Occurrence of cancer through 1993 was
      determined by linkage to the Danish Cancer Registry. For comparison, the expected
      number of cancer cases was estimated from national age-, sex-, and site-specific
      incidence rates. Overall, 1,447 cancers were diagnosed among the study subjects,
      as compared with 708.1 expected, to yield a standardized incidence ratio (SIR) of
      2.0 (95% CI: 1.9 to 2.2). In all diagnostic subgroups of cirrhosis, the risk of
      primary liver cancer, mainly hepatocellular carcinoma, was markedly elevated,
      with 245 observed cases and an overall 36-fold elevated risk (59.9-fold elevated
      for hepatocellular carcinoma and 10-fold for cholangiocarcinoma). Substantial and
      persistent excesses during follow-up were seen for all types of cancer associated
      with tobacco and alcohol habits (cancer of the lung, larynx, buccal cavity,
      pharynx, pancreas, urinary bladder, and kidney), while moderate excesses were
      seen for cancers of the colon and breast. The latter, however, were not
      complemented by any decrease in the risk of prostate cancer (SIR: 1.0; 95% CI:
      0.7 to 1. 3). A slightly increased risk was seen for testis cancer, but
      disappeared after 10 years. We found evidence of an increased risk for liver and
      several extrahepatic cancers in patients with cirrhosis. Although part of this
      increase is likely attributable to alcohol and tobacco consumption, our study
      opens up the possibility that cirrhosis plays a role in the carcinogenesis of
      types of cancer other than liver cancer.

PMID- 9755227
TI  - Endothelial dysfunction and decreased production of nitric oxide in the
      intrahepatic microcirculation of cirrhotic rats.
AB  - Increased intrahepatic resistance in cirrhotic livers is in part caused by
      increased vascular tone. Several morphological abnormalities have been described
      in the sinusoidal endothelial cells of cirrhotic livers, but the functional
      impact of these abnormalities on the intrahepatic vascular tone has not been
      studied. The aim of this study was to investigate the intrahepatic endothelial
      function and the role of nitric oxide (NO) with regard to vascular tone in
      cirrhotic livers. Isolated rat liver perfusions were performed in cirrhotic rats
      (induced by chronic carbon tetrachloride inhalation) and weight-matched normal
      controls. After preconstricting the intrahepatic microcirculation with
      methoxamine (10(-4) mol/L), response to cumulative doses of receptor-mediated
      endothelial agonist, acetylcholine (10(-7) mol/L-10(-5) mol/L), was obtained. In
      another series, response to the receptor-independent endothelial agonist, calcium
      ionophore A23187 (10(-7) mol/L and 3 x 10(-7) mol/L), was obtained in the absence
      and presence of Nomega-nitro-L-arginine (NNA) and indomethacin. In a third series
      of rats, nitrate and nitrite production was measured in the perfusate of perfused
      normal and cirrhotic livers. There was significantly less vasorelaxation in
      cirrhotic livers as compared with normal livers in response to acetylcholine and
      calcium ionophore A23187 (P < .0001). The impaired vasorelaxation was a result of
      a decrease in both NO-mediated and non-NO-mediated components of vasorelaxation.
      Cirrhotic livers from ascitic rats had significantly less vasorelaxation as
      compared with livers from nonascitic rats (P < .005). There was significantly
      less production of nitrates and nitrites in cirrhotic livers (P < .05). The liver
      microcirculation of cirrhotic livers is characterized by endothelial dysfunction
      that results in impaired release of endothelial relaxing factors including NO.

PMID- 9755228
TI  - Doppler study of mesenteric, hepatic, and portal circulation in alcoholic
      cirrhosis: relationship between quantitative Doppler measurements and the
      severity of portal hypertension and hepatic failure.
AB  - To determine the relationship between quantitative Doppler parameters of portal,
      hepatic, and splanchnic circulation and hepatic venous pressure gradient (HVPG),
      variceal size, and Child-Pugh class in patients with alcoholic cirrhosis, we
      studied forty patients with proved alcoholic cirrhosis who underwent Doppler
      ultrasonography, hepatic vein catheterization, and esophagoscopy. The following
      Doppler parameters were recorded: time-averaged mean blood velocity, volume flow
      of the main portal vein flow, and resistance index (RI) of the hepatic and of the
      superior mesenteric artery. Doppler findings were compared with HVPG, presence
      and size of esophageal varices, and Child-Pugh class. There was a significant
      inverse correlation between portal velocity and HVPG (r = -.69), as well as
      between portal vein flow and HVPG (r = -.58). No correlation was found between RI
      in the hepatic artery or superior mesenteric artery and HVPG. No correlation was
      found between portal vein measurements and presence and size of varices. Severe
      liver failure was associated with lower portal velocity and flow. In patients
      with alcoholic cirrhosis, only portal vein blood velocity and flow, but neither
      hepatic nor mesenteric artery RI, are correlated to the severity of portal
      hypertension and to the severity of liver failure.

PMID- 9755229
TI  - Acute effects of the oral administration of midodrine, an alpha-adrenergic
      agonist, on renal hemodynamics and renal function in cirrhotic patients with
      ascites.
AB  - The effects of the acute administration of arterial vasoconstrictors on renal
      plasma flow (RPF) and urinary sodium excretion (UNaV) in cirrhotic patients with
      ascites with or without hepatorenal syndrome (HRS) are still controversial. As a
      consequence, vasoconstrictors are not actually used in the treatment of renal
      sodium retention or HRS in these patients, regardless of the several lines of
      evidence suggesting that these renal functional abnormalities are related to a
      marked arterial vasodilation. The lack of an orally available effective arterial
      vasoconstrictor probably represents a further reason for this omission.
      Consequently, the present study was made to evaluate the acute effects of the
      oral administration of midodrine, an orally available -mimetic drug, on systemic
      and renal hemodynamics and on UNaV in cirrhotic patients with ascites. Mean
      arterial pressure (MAP), heart rate (HR), cardiac index (CI), systemic vascular
      resistance (SVR), left forearm blood flow (LFBF), left leg blood flow (LLBF),
      RPF, glomerular filtration rate (GFR), UNaV, plasma renin activity (PRA), plasma
      concentration of antidiuretic hormone (ADH), and the serum levels of nitrite and
      nitrate (NOx) were evaluated in 25 cirrhotic patients with ascites (17 without
      HRS and 8 with type 2 HRS) before and during the 6 hours following the oral
      administration of 15 mg of midodrine. During the first 3 hours after the drug
      administration, a significant increase in MAP (89.6 +/- 1.7 vs. 81.80 +/- 1.3 mm
      Hg; P < .0001) and SVR (1, 313.9 +/- 44.4 vs. 1,121.2 +/- 60.1 dyn . sec . cm-5;
      P < .0001) accompanied by a decrease in HR (69 +/- 2 vs. 77 +/- 3 bpm; P < .005)
      and CI (2,932.7 +/- 131.4 vs. 3,152.5 +/- 131.4 mL . min-1 . m2 BSA; P < .0025)
      was observed in patients without HRS. No change was observed in LFBF and LLBF.
      The improvement in systemic hemodynamics, which was also maintained during the
      the 3- to 6-hour period after midodrine administration, was accompanied by a
      significant increase in RPF (541.5 +/- 43.1 vs. 385.7 +/- 39.9 mL . min-1; P <
      .005), GFR (93.1 +/- 6.5 vs. 77.0 +/- 6.7 mL . min-1; P < .025), and UNaV (92.7
      +/- 16.4 vs. 72.2 +/- 10.7 microEq . min-1; P < .025). In addition, a decrease in
      PRA (5.33 +/- 1.47 vs. 7.74 +/- 2.17 ng . mL-1 . h; P < .05), ADH (1.4 +/- 0.2
      vs. 1.7 +/- 0.2 pg . mL-1; P < .05), and NOx (33.4 +/- 5.0 vs. 49.3 +/- 7.3
      micromol-1; P < .05) was found. In patients with HRS, the effects of the drug on
      the systemic hemodynamics was smaller and shorter. Accordingly, regardless of a
      significant decrease in PRA (15.87 +/- 3.70 vs. 20.70 +/- 4.82 ng . mL-1 . h; P <
      .0025) in patients with HRS, no significant improvement was observed in RPF, GFR,
      or UNaV. In conclusion, the acute oral administration of midodrine is associated
      with a significant improvement in systemic hemodynamics in nonazotemic cirrhotic
      patients with ascites. As a result, renal perfusion and UNaV also improve in
      these patients. By contrast, midodrine only slightly improves systemic
      hemodynamics in patients with type 2 HRS, with no effect on renal hemodynamics
      and renal function.

PMID- 9755230
TI  - Gene expression of alpha1-6 fucosyltransferase in human hepatoma tissues: a
      possible implication for increased fucosylation of alpha-fetoprotein.
AB  - The 1-6 fucosylated -fetoprotein (AFP) present in serum of patients with
      hepatocellular carcinoma (HCC) has been employed for the differential clinical
      diagnosis of HCC from chronic liver diseases. The molecular mechanism by which
      this alteration occurs, however, remains largely unknown. To address this issue,
      we purified GDP-L-Fuc:N-acetyl-beta-D-glucosaminide 1-6 fucosyltransferase (1-6
      FucT), an enzyme involved in the 1-6 fucosylation of N-glycans from porcine
      brain, as well as from a human gastric cancer cell line, and cloned their genes.
      In this study, levels of 1-6 FucT mRNA expression and the activity of this enzyme
      for 12 human HCC tissues were examined and compared with that in surrounding
      tissues and normal livers. The mean +/- SD for 1-6 FucT activity was 78 +/- 41
      pmol/h/mg in normal control liver, 202 +/- 127 pmol/h/mg in adjacent uninvolved
      liver tissues (chronic hepatitis: 181 +/- 106 pmol/h/mg; liver cirrhosis: 233 +/-
      164 pmol/h/mg), and 195 +/- 72 pmol/h/mg in HCC tissues. The mRNA expression of 1
      6 FucT was also enhanced in proportion to enzymatic activity except for a few
      cases, suggesting that 1-6 FucT expression is increased in chronic liver
      diseases, especially liver cirrhosis. Transfection of 1-6 FucT gene into cultured
      rat hepatocytes markedly increased 1-6 FucT activity and led to an increase in
      lens culinaris agglutinin (LCA) binding proteins in both cell lysates and
      condition media. When the 1-6 FucT gene was transfected into a human HCC cell
      line, Hep3B, which originally showed low levels of 1-6 FucT expression, 1-6
      fucosylated AFP was dramatically increased in the condition media. Collectively,
      these results suggest that the enhancement of 1-6 FucT expression increased the
      fucosylation of several proteins, including AFP, and that the level of 1-6
      fucosylated AFP in patients with HCC was in part caused by up-regulation of the 1
      6 FucT gene expression.

PMID- 9755231
TI  - Clonal analysis of macronodules in cirrhosis.
AB  - Several arguments suggest that most hepatocellular carcinomas (HCCs) occurring in
      human cirrhotic livers arise from large hepatocellular nodules or macronodules.
      Except for nodules with obvious features of HCC, there exist no consistent
      criteria enabling the differentiation between benign regenerative and neoplastic,
      potentially malignant macronodules. Surrogate markers able to accurately
      discriminate those lesions that will evolve toward a HCC are required. In this
      study, we investigated the clonality of 26 macronodules isolated from eight cases
      of explanted cirrhotic livers in women by analyzing X-chromosome inactivation, as
      indicated by the methylation status of the human androgen receptor gene (HUMARA).
      For each macronodule, a large set of pathological features was evaluated and used
      to classify the macronodules into four groups: entirely benign-looking nodule
      (type 1), low-grade dysplastic nodule (type 2), high-grade dysplastic nodule
      (type 3), and HCC (type 4). Clonal analysis showed that 14 macronodules (54%)
      were monoclonal and 12 (46%) were polyclonal. Monoclonality was detected in 5 of
      11 (45%) nodules from groups of entirely benign-looking and low-grade dysplastic
      nodules (types 1 and 2) and in 9 of 15 (60%) nodules from the group of high-grade
      dysplastic nodule and HCC (types 3 and 4). Neither the etiology of cirrhosis nor
      the size or histological classification of macronodules was correlated with the
      clonal status. In conclusion, clonal analysis of macronodules enables the
      differentiation between mono- and polyclonal macronodules in cirrhosis. Because
      monoclonal macronodules are prone to evolve to HCC, the determination of the
      clonal status of a macronodule could provide additional information for
      evaluating the prognosis of these lesions.

PMID- 9755232
TI  - Analysis of liver regeneration in mice lacking type 1 or type 2 tumor necrosis
      factor receptor: requirement for type 1 but not type 2 receptor.
AB  - We used KO mice lacking either TNF receptor 1 (TNFR-1) or receptor 2 (TNFR-2) to
      determine whether signaling at the start of liver regeneration after partial
      hepatectomy (PH) involves only one or both TNF receptors and to analyze in more
      detail the abnormalities caused by lack of TNFR-1 receptor, which is required for
      the initiation of liver regeneration. Lack of TNFR-2 had little effect on NF
      kappaB and STAT3 binding, and no effect in interleukin-6 production after PH, but
      caused a delay in AP-1 and C/EBP binding and in the expression of c-jun and c-myc
      messenger RNA (mRNA). In contrast to mice lacking TNFR-1, which had deficient
      hepatocyte DNA synthesis and massive lipid accumulation in hepatocytes, TNFR-2 KO
      mice had normal liver structure and similar levels of hepatocyte DNA replication
      as those of wild type mice. We conclude that TNFR-1, but not TNFR-2, is necessary
      for liver regeneration, and that NF-kappaB and STAT3 binding are activated by
      signals transduced by TNFR-1. Inhibition of AP-1 and C/EBP binding and in the
      expression of c-jun and c-myc mRNA in the first 4 hours after PH, as well as the
      apparent lack of Fos in AP-1 complexes, had no effect on the timing or extent of
      DNA replication.

PMID- 9755233
TI  - Clinical relevance of transforming growth factor alpha, epidermal growth factor
      receptor, p53, and Ki67 in colorectal liver metastases and corresponding primary
      tumors.
AB  - To determine whether the expression of transforming growth factor alpha (TGF
      alpha), its receptor (epidermal growth factor receptor [EGFr]), p53 nuclear
      protein, and proliferation influences prognosis of patients with liver
      metastases, a study was performed in 45 liver metastases and 33 corresponding
      primary colorectal carcinomas in patients referred for liver surgery. The
      expression of TGF-alpha, EGFr, p53 nuclear protein, and proliferation rate was
      correlated with clinicopathological characteristics and survival after partial
      liver resection. In liver metastases, TGF-alpha expression was low in 42%,
      intermediate in 35%, and high in 23%. TGF-alpha expression was higher in liver
      metastases derived from lymph node-positive primary carcinomas, in synchronous
      and in irresectable liver metastases compared with those derived from lymph node
      negative primary carcinomas, metachronous, and resectable liver metastases.
      Nuclear p53 expression was found in 83% of primary tumors and 71% of liver
      metastases. p53 expression did not correlate with the various clinicopathological
      characteristics. Ki67 expression was not associated with clinicopathological
      characteristics in primary and metastatic tumors. In the 38 patients in whom a
      partial liver resection was performed, median survival was 25 months in patients
      with a higher TGF-alpha expression in the metastasis than in the primary tumor
      and 60 months in patients with comparable or lower TGF-alpha expression in the
      metastasis than in the primary tumor (P = .036). Median survival after liver
      resection was 21 months in patients with p53-negative liver metastases and 58
      months in patients with p53-positive metastases (P = .043). By multivariate
      analysis, p53 and EGFr expression on liver metastases were the best predictors of
      disease-free survival after partial liver resection, with relative risks of 2.38
      and 3.33, respectively. In patients with colorectal liver metastases, referred
      for liver surgery, a higher TGF-alpha expression is associated with unfavorable
      tumor characteristics, whereas p53 and absence of EGFr expression is associated
      with a better survival after partial liver resection.

PMID- 9755234
TI  - Immunolocalization of OV-6, a putative progenitor cell marker in human fetal and
      diseased pediatric liver.
AB  - The existence of progenitor (stem) cells in the human liver remains a matter of
      debate. In rodent models of hepatocarcinogenesis and injury, oval cells
      proliferate in the periportal regions of the portal tracts and are suggested to
      derive from a stem cell compartment, because they are capable of differentiating
      into hepatocytes or biliary epithelial cells. In this study, the rat oval cell
      marker, OV-6 has been used to investigate the hypothesis that there are stem
      cells present in fetal and pediatric human liver. The pattern of OV-6 expression
      was compared with the established adult biliary cell markers human epithelial
      antigen-125 (HEA-125) and cytokeratin-19 (CK-19). In normal pediatric liver (n =
      7), bile ducts and ductules were immunostained with CK-19 and HEA-125, whereas OV
      6 staining was consistently negative. In fetal tissue (n = 10), ductal plate
      cells, primitive bile ducts, and hepatoblasts were stained with CK-19 and HEA-125
      although only some of the ductal plate cells and hepatoblasts were OV-6 positive.
      In biliary atresia (n = 6) and 1, anti-trypsin deficiency (1,AT) (n = 4), CK-19
      and HEA-125 immunostained ductular proliferative cells that tended to form finely
      anastomosing ductules, whereas OV-6 staining was found more on discrete cells
      confined to portal tract margins. Additionally, in diseased liver, OV-6 was
      strongly positive in hepatocyte lobules with greatest intensity in the periseptal
      regions. This widespread hepatocyte OV-6 positivity suggests that the antibody
      may identify cells of a less differentiated phenotype (transitional hepatocytes)
      that have replaced the mature cells. Therefore, it is proposed that in human
      liver, OV-6 is recognizing cells with a progenitor stem cell-like phenotype with
      the capacity to differentiate into OV-6 positive ductular cells or lobular
      hepatocytes.

PMID- 9755236
TI  - Interaction between heat shock and interleukin 6 stimulation in the acute-phase
      response of human hepatoma (HepG2) cells.
AB  - Two characteristic elements of the acute-phase response are an altered pattern of
      circulating hepatic proteins and fever. Whereas a fever-induced heat shock
      response could affect expression of acute-phase proteins in the liver, the
      effects of a modest temperature increase on protein secretion in interleukin-6
      (IL-6)-stimulated HepG2 cells were investigated. The response of HepG2 cells to
      IL-6 stimulation was significantly affected by heat treatment at 40 degreesC.
      Albumin secretion rates, which were reduced by a factor of 2 in response to
      either heat shock or IL-6 stimulation alone, were down-regulated by a factor of 4
      when IL-6 was administered simultaneously with a continuous 40 degrees C heat
      shock. IL-6-induced fibrinogen up-regulation was significantly reduced by heat
      treatment (P < .01), and secretion rates were indistinguishable from control
      levels after 2 days (P > .10). Unexpectedly, heat shock at 40 degrees C induced a
      fivefold up-regulation of haptoglobin production in the absence of IL-6.
      Simultaneous heat shock and IL-6 stimulation caused a synergistic enhancement of
      haptoglobin expression, with secretion rates increasing up to 30-fold compared
      with unstimulated control cells. For all three proteins, the interaction between
      temperature and IL-6 concentration was statistically significant (P < .001). Heat
      treatment resulted in significant alterations of both the kinetics and
      sensitivity of IL-6-induced protein synthesis, suggesting a major modification of
      the mechanism of acute-phase protein regulation at 40 degreesC. In summary, the
      data show that heat shock can significantly modulate the pattern of acute-phase
      protein expression and that fever may be an important regulatory factor in the
      acute-phase response.

PMID- 9755235
TI  - Expression of human macrophage metalloelastase gene in hepatocellular carcinoma:
      correlation with angiostatin generation and its clinical significance.
AB  - Macrophage metalloelastase, a member of the human matrix metalloproteinase
      family, is believed to play an important role in angiostatin generation, which,
      in experimental studies, has an antiangiogenic function and is a key molecule in
      tumor dormancy. However, no clinical studies have been reported regarding the
      correlation between human macrophage metalloelastase (HME) gene expression and
      angiostatin production. Therefore, the present study was designed to evaluate the
      HME messenger RNA (mRNA) expression and angiostatin generation in hepatocellular
      carcinoma (HCC). Tumorous and contiguous nontumorous tissues were obtained from
      40 HCC patients who underwent curative partial hepatectomy. By using Northern
      blot hybridization, HME mRNA was detected in 25 of the 40 HCC samples and, in all
      of these cases, the expression in tumorous tissues was stronger than in the
      nontumorous tissues. In situ hybridization identified the HCC cells as mainly
      responsible for the signals shown in Northern blot. Angiostatin was detected by
      Western blot mainly in tumors and showed significant association with HME mRNA
      expression in tumorous tissues (P = .0008). The patients whose tumors did not
      express HME mRNA and, thus, did not produce angiostatin, demonstrated poorer
      survival than those whose tumors showed high expression of HME mRNA and
      angiostatin generation (P = . 002). The univariate and multivariate analyses
      revealed that HME mRNA expression is a new and independent variable affecting
      overall survival (P = .001 and P = .03, respectively). These findings show that
      the HME gene is expressed in HCC being significantly associated with angiostatin
      generation by such tumors and that HME mRNA expression may serve as a new
      molecular prognostic marker in HCC patients after partial hepatectomy.

PMID- 9755237
TI  - Efficacy of anti-intercellular adhesion molecule-1 immunotherapy on immune
      responses to allogeneic hepatocytes in mice.
AB  - Adhesion molecules appear to play important roles in vascularized organ allograft
      rejection, because antibodies directed against them are effective in prolonging
      survival of vascularized organ allografts in rodents. However, the efficacy of
      these agents for cellular allografts is unknown. The current studies were
      undertaken to determine the role of intercellular adhesion molecule-1 (ICAM-1)
      and vascular cell adhesion molecule-1 (VCAM-1) on host immune responses to
      purified hepatocytes. Host mice (C3H, H-2(k)) grafted with hepatocytes in sponge
      matrix allografts (HC-SMA) received IgG isotype control, anti-ICAM-1, or anti
      VCAM-1 monoclonal antibody (mAb) on days 0 through 9 after grafting. Twelve to 14
      days later, host cells infiltrating the HC-SMA were assessed for the development
      of allospecific cytolytic T cells (allo-CTLs). Treatment with anti-ICAM-1 or anti
      VCAM-1 mAb resulted in significantly decreased recruitment of host cells into HC
      SMA (P < .035). However, only anti-ICAM-1 mAb resulted in abrogation of
      development of allo-CTLs in HC-SMA (P = .001). C3H (H-2(k)) hosts grafted with
      allogeneic hepatocytes from control C57BL/6 (H-2(b)) or ICAM-1 knockout [H-2(b)]
      mice elicited the development of allo-CTLs in HC-SMA (P = not significant).
      Furthermore, there was no difference in the development of allo-CTLs in HC-SMA of
      control hosts [C57BL/6, H-2(b)] compared with ICAM-1 knockout hosts (H-2(b)) (P =
      not significant). Treatment with anti-ICAM-1 mAb had no effect on the development
      of allo-CTLs in ICAM-1 knockout (H-2(b)) hosts bearing HC-SMA. The
      immunosuppressive effect of host treatment with anti-ICAM-1 mAb does not appear
      to be a consequence of simple blockage of donor hepatocyte or host immune cell
      expression of ICAM-1, but suggests a potential inhibitory effect on host immune
      cell activation or function, as well as an effect on recruitment of host cells to
      the allograft.

PMID- 9755238
TI  - The hepatitis B virus X protein up-regulates tumor necrosis factor alpha gene
      expression in hepatocytes.
AB  - Human hepatocytes infected by hepatitis B virus (HBV) produce the proinflammatory
      cytokine, tumor necrosis factor (TNF-). In this study, we explored the mechanism
      of induction of TNF- synthesis by HBV. We found that the stable HBV-transfected
      hepatoma cell line, 2. 2.15, expressed high-molecular-weight (HMW) TNF- mRNAs,
      which were absent in the parent HepG2 cells. Treatment of 2.2.15 cells with
      interferon alfa (IFN-) and/or interleukin-1beta (IL-1beta) reduced both viral
      gene transcription and TNF- mRNA expression. Transient or stable transfection of
      hepatocyte-derived cell lines with HBV X protein (HBx) expression vectors induced
      the production of biologically active TNF-. In these cells, the HBx-induced TNF-
      was detected both as cell-associated and soluble forms. Luciferase gene
      expression assays showed that the TNF- gene promoter contained target sequences
      for HBx trans-activation within the proximal region of the promoter. These
      results indicate that the hepatocyte TNF- synthesis induced by HBV is
      transcriptionally up-regulated by HBx. Thus, HBx may have a role in the induction
      of the intrahepatic inflammatory processes that take place during acute and
      chronic hepatitis B.

PMID- 9755239
TI  - Ischemia/reperfusion injury in the liver of BALB/c mice activates AP-1 and
      nuclear factor kappaB independently of IkappaB degradation.
AB  - For many inherited and acquired hepatic diseases, liver transplantation is the
      only possible therapeutic strategy. Ischemia/reperfusion (I/R) damage to donor
      tissue is thought to be one component that may play a role in the decline of
      posttransplant tissue function and ultimately rejection. The transcription
      factors, AP-1 and nuclear factor kappaB (NF-kappaB), play important roles in the
      acute cellular responses to tissue damage, as well as the inflammatory phase
      following I/R. We have found that the DNA binding activity of AP-1 was
      dramatically increased following warm ischemia at 1 to 3 hours postreperfusion.
      Induced DNA binding activity was composed of predominately c-Jun and JunD hetero-
      and homodimers as determined by electrophoretic mobility supershift assays. This
      increase in AP-1 activity occurred in the absence of significant changes in the
      steady-state protein levels of c-Jun and JunB. Maximal activation of Jun amino
      terminal kinase ( JNK) occurred within the 25 to 30 minutes postreperfusion, just
      before the peak in AP-1 DNA binding. These findings suggest that phosphorylation
      may play an important role in regulating AP-1 transcriptional complexes.
      Furthermore, JunD protein levels slightly increased at 3 hours postreperfusion,
      concordant with changes in AP-1 DNA binding activity. The activation of NF-kappaB
      at 1 hour postreperfusion was independent of proteolytic degradation of IkappaB-
      or IkappaB-beta. This activation of NF-kappaB DNA binding activity in the nucleus
      was preceded by an increase in tyrosine phosphorylation of IkappaB-. These
      studies suggest that JNK, IkappaB tyrosine kinase, and JunD are potential targets
      for therapeutic intervention during liver I/R injury.

PMID- 9755240
TI  - Vasopressin-induced disruption of actin cytoskeletal organization and canalicular
      function in isolated rat hepatocyte couplets: possible involvement of protein
      kinase C.
AB  - The effect of vasopressin (VP) on canalicular function and hepatocellular
      morphology, with particular regard to actin cytoskeletal organization and the
      concomitant plasma membrane bleb formation, was studied in isolated rat
      hepatocyte couplets. VP induced the concentration-dependent formation of multiple
      plasma membrane blebs as well as simultaneous impairment in both canalicular
      vacuolar accumulation (cVA) and retention (cVR) of the fluorescent bile acid,
      cholyl-lysyl-fluorescein (CLF), which evaluate couplet secretory function and
      tight-junction integrity, respectively. These effects were mimicked by the
      protein kinase C (PKC) activator, phorbol dibutyrate (PDB), but not by the
      protein kinase A (PKA) activator, dibutyryl-cAMP. VP-induced bleb formation and
      canalicular dysfunction were fully prevented by the protein kinase inhibitor, H
      7, but not by the PKA inhibitor, KT5720, further suggesting a specific role of
      PKC. VP-induced alterations were also prevented by pretreatment with the Ca2+
      buffering agent, BAPTA/AM, but not with the calmodulin-dependent protein kinase
      II antagonist, calmidazolium. Neither the Ca2+-activated neutral protease
      inhibitor, leupeptin, nor the antioxidants, alpha-tocopherol or deferoxamine,
      were able to prevent either VP-induced plasma membrane blebbing or canalicular
      dysfunction. The Ca2+-ionophore, A23187, mimicked the VP-induced alterations, but
      its harmful effects were completely prevented by H-7. Bleb formation induced by
      VP and PDB was accompanied by an extensive redistribution of filamentous actin
      from the pericanalicular area to the cell body, and this effect was fully
      prevented by H-7. These results suggest that VP-induced canalicular and
      cytoskeletal dysfunction is mediated by PKC and that classical (Ca2+-dependent)
      PKC appear to be involved because intracellular Ca2+ is required for VP to induce
      its harmful effects.

PMID- 9755241
TI  - Dietary juniper berry oil minimizes hepatic reperfusion injury in the rat.
AB  - Juniper berry oil is rich in 5,11,14-eicosatrienoic acid, a polyunsaturated fatty
      acid similar to one found in fish oil, yet less prone to peroxidation. Dietary
      fish oil treatment has been shown to effectively reduce reperfusion injury;
      therefore, the effects of a diet containing juniper berry oil on hepatic
      reperfusion injury in a low-flow, reflow reperfusion model were investigated in
      the rat. Rats were fed semisynthetic diets containing either juniper berry oil,
      fish oil, or corn oil for 14 to 16 days. Daily food consumption averaged around
      20 g/d in both the control and treatment groups; average daily weight gain was
      around 4 g per 100 g rat weight in all three groups studied, and there were no
      significant differences in these parameters. Livers were initially perfused at
      low-flow rates to induce pericentral hypoxia followed by a 40-minute reperfusion
      period. Peak lactate dehydrogenase (LDH) release during reflow averaged 44 U/g/h
      in the corn oil group and 32 U/g/h in the fish oil group, but was only 21 U/g/h
      as a result of juniper berry oil treatment. Malondialdehyde (MDA), an end-product
      of lipid peroxidation, reached a maximum value of 62 nmol/g/h in the corn oil
      group, but only reached 43 nmol/g/h and 34 nmol/g/h in the fish oil and juniper
      berry oil groups, respectively. Both juniper berry oil and fish oil treatment
      improved rates of bile flow from 25 microL/g/h (corn oil) to 36 and 38
      microL/g/h, respectively. Importantly, juniper berry oil reduced cell death in
      pericentral regions of the liver lobule by 75%. Trypan blue distribution time, an
      indicator of the hepatic microcirculation, was reduced by approximately 25% with
      fish oil and over 50% by juniper berry oil diets compared with corn oil controls.
      The rates of entry of fluorescein-dextran, a dye confined to the vascular space,
      were increased 1.8- and 2.6-fold, and rates of outflow were increased 4.4- and
      4.3-fold by fish oil and juniper berry oil, respectively, also reflecting
      improved microcirculation. Juniper berry oil also blunted increases in
      intracellular calcium and release of prostaglandin E2 (PGE2) by cultured Kupffer
      cells stimulated by endotoxin. These results are consistent with the hypothesis
      that feeding a diet containing juniper berry oil reduces reperfusion injury by
      inhibiting activation of Kupffer cells, thus reducing vasoactive eicosanoid
      release and improving the hepatic microcirculation in livers undergoing oxidant
      stress.

PMID- 9755242
TI  - Nitric oxide inactivates rat hepatic methionine adenosyltransferase In vivo by S
      nitrosylation.
AB  - We investigated the mechanism of nitric oxide (NO) action on hepatic methionine
      adenosyltransferase (MAT) activity using S-nitrosoglutathione (GSNO) as NO donor.
      Hepatic MAT plays an essential role in the metabolism of methionine, converting
      this amino acid into S-adenosylmethionine. Hepatic MAT exists in two oligomeric
      states: as a tetramer (MAT I) and as a dimer (MAT III) of the same subunit. This
      subunit contains 10 cysteine residues. In MAT I, S-nitrosylation of 1 thiol
      residue per subunit was associated with a marked inactivation of the enzyme
      (about 70%) that was reversed by glutathione (GSH). In MAT III, S-nitrosylation
      of 3 thiol residues per subunit led to a similar inactivation of the enzyme,
      which was also reversed by GSH. Incubation of isolated rat hepatocytes with S
      nitrosoglutathione monoethyl ester (EGSNO), a NO donor permeable through the
      cellular membrane, induced a dose-dependent inactivation of MAT that was reversed
      by removing the NO donor from the cell suspension. MAT, purified from isolated
      rat hepatocytes, contained S-nitrosothiol groups and the addition of increasing
      concentrations of EGSNO to the hepatocyte suspension led to a progressive S
      nitrosylation of the enzyme. Removal of the NO donor from the incubation media
      resulted in loss of most NO groups associated to the enzyme. Finally, induction
      in rats of the production of NO, by the administration of bacterial
      lipopolysaccharide (LPS), induced a fivefold increase in the S-nitrosylation of
      hepatic MAT, which led to a marked inactivation of the enzyme. Thus, the activity
      of liver MAT appears to be regulated in vivo by S-nitrosylation.

PMID- 9755243
TI  - Increased risk of chronic liver failure in adults with heterozygous alpha1
      antitrypsin deficiency.
AB  - Controversy exists whether patients who are genetically heterozygous for 1
      antitrypsin deficiency (1ATD), carrying a single PI*Z allele, are at increased
      risk of developing chronic liver disease. In these investigations, we determined
      the prevalence of heterozygous 1AT phenotypes (PI MZ, PI SZ) in a well
      characterized cohort of patients presenting with chronic liver failure before
      orthotopic liver transplantation (OLT). We analyzed data collected from all adult
      patients (n = 641) who underwent OLT at our tertiary referral center between
      March 1985 and December 1996. Study patients entered a prospective protocol
      designed to test for all known etiologies of liver disease. Complete testing
      including 1AT phenotyping was successfully performed in 599 adults. We compared
      the overall number of heterozygous PI*Z carriers in our OLT cohort with
      established prevalence figures for general and regional American populations, and
      examined their distribution among various liver disease subgroups. Fifty-one
      patients were found to be heterozygous carriers of a single PI*Z allele for 1AT.
      The predominant phenotype in our transplantation cohort was PI MZ, identified in
      49 patients (8.2%), which is a significantly higher prevalence than that reported
      from previous American population studies (2%-4%). Additionally, a significantly
      greater number of PI MZ carriers existed in patients with cryptogenic cirrhosis
      compared with other liver disease categories (26.9%; P < .001). These data
      suggest that individuals carrying a single PI*Z allele for 1AT may be at
      increased risk of developing cirrhosis and liver failure, even in the absence of
      an identifiable coexisting liver disease.

PMID- 9755244
TI  - Cholesterol 7alpha-hydroxylase (CYP7A): patterns of messenger RNA expression
      during rat liver development.
AB  - Cholesterol 7-hydroxylase is a rate-limiting enzyme in bile acid synthesis, a
      major pathway for cholesterol catabolism. It plays a crucial role in postnatal
      development and survival. In an adult liver, its activity and messenger RNA
      (mRNA) are heterogeneously distributed with concentration in the pericentral
      area. We defined how the pattern of cholesterol 7-hydroxylase mRNA evolves during
      rat liver development, correlated this with its total liver mRNA levels, and
      determined when its heterogeneous pattern of expression is established.
      Cholesterol 7-hydroxylase mRNA was undetectable in 18-day-old fetal livers by
      Northern blot. It was increased markedly in newborns with a homogeneous liver
      lobular distribution as determined by in situ hybridization. At postnatal day
      four, mRNA levels were markedly decreased with concomitant appearance of a
      lobular gradient: mRNA was detected only in a few hepatocytes located around
      efferent venules. At 22 days, the time of highest mRNA expression, a marked
      extension of the gradient towards the periportal area was observed, indicating
      that the increase in total liver cholesterol 7-hydroxylase mRNA level was a
      result of recruitment of hepatocytes upstream from the central vein area. By 28
      days, the adult pattern was observed. Thus, expression of cholesterol 7
      hydroxylase mRNA is tightly regulated during rat liver development, both
      temporally and spatially supporting its critical role in normal postnatal
      development.

PMID- 9755245
TI  - Activation of protein kinase Calpha couples cell volume to membrane Cl-
      permeability in HTC hepatoma and Mz-ChA-1 cholangiocarcinoma cells.
AB  - Physiological increases in liver cell volume lead to an adaptive response that
      includes opening of membrane Cl- channels, which is critical for volume recovery.
      The purpose of these studies was to assess the potential role for protein kinase
      C (PKC) as a signal involved in cell volume homeostasis. Studies were performed
      in HTC rat hepatoma and Mz-ChA-1 human cholangiocarcinoma cells, which were used
      as model hepatocytes and cholangiocytes, respectively. In each cell type, cell
      volume increases were followed by: 1) translocation of PKC from cytosolic to
      particulate (membrane) fractions; 2) a 10- to 40-fold increase in whole-cell
      membrane Cl- current density; and 3) partial recovery of cell volume. In HTC
      cells, the volume-dependent Cl- current response (-46 +/- 5 pA/pF) was inhibited
      by down-regulation of PKC (100 nmol/L phorbol 12-myristate 13-acetate for 18
      hours [PMA]; -1.97 +/- 1.5 pA/pF), chelation of cytosolic Ca2+ (2 mmol/L EGTA; 
      5.3 +/- 4.0 pA/pF), depletion of cytosolic adenosine triphosphate (ATP) (3 U/mL
      apyrase; -12.58 +/- 1. 45 pA/pF), and by the putative PKC inhibitor,
      chelerythrine (25 micromol/L; -7 +/- 3 pA/pF). In addition, PKC inhibition by
      chelerythrine and calphostin C (500 nmol/L) prevented cell volume recovery from
      swelling. Similar results were obtained in Mz-ChA-1 biliary cells. These findings
      indicate that swelling-induced activation of PKC represents an important signal
      coupling cell volume to membrane Cl- permeability in both hepatic and biliary
      cell models.

PMID- 9755246
TI  - Neither intestinal sequestration of bile acids nor common bile duct ligation
      modulate the expression and function of the rat ileal bile acid transporter.
AB  - The regulatory responses of bile acid (BA) transport in the terminal ileum to
      perturbations in BA homeostasis are complex, and conflicting results have been
      reported by different investigators. These studies were designed to examine the
      response of this system to a reduction in ileal bile salt concentrations at both
      a functional and molecular level. Common bile duct ligation (BDL) or feeding of a
      novel bile acid-binding compound, GT31-104HB, for 7 days were used to reduce
      ileal apical membrane bile salt flux. Apical bile acid transport function was
      assessed by examining sodium-dependent uptake of [3H]-taurocholate (TC) into
      brush border membrane vesicles (BBMV). Expression of the apical sodium-dependent
      bile acid transporter (ASBT) and the ileal lipid-binding protein (ILBP) were
      assessed by Western blotting with quantitation using [125I]-labeled secondary
      antibody and a phosphorimager. Neither common BDL nor intestinal sequestration of
      BA led to a change in ileal bile acid transport function or the expression of the
      ASBT or the ILBP. These results indicate that a reduction in presentation of bile
      salts to the apical surface of the terminal ileum does not modulate the
      expression of the genes involved in their transport.

PMID- 9755247
TI  - Gender-related differences in bile acid and sterol metabolism in outbred CD-1
      mice fed low- and high-cholesterol diets.
AB  - These studies were undertaken to determine whether in young adult outbred CD-1
      mice there were any gender-related differences in basal bile acid metabolism that
      might be important in determining how males and females in this species responded
      to a dietary cholesterol challenge. When fed a plain cereal-based rodent diet
      without added cholesterol, 3-month-old females, compared with age-matched males,
      manifested a significantly larger bile acid pool (89.1 vs. 54.1 micromol/100 g
      body weight), a higher rate of fecal bile acid excretion (13.6 vs. 8.5
      micromol/d/100 g body weight), a more efficient level of intestinal cholesterol
      absorption (41.1% vs. 25. 3%), and a lower rate of hepatic sterol synthesis (338
      vs. 847 nmol/h/g). Similar results were found in C57BL/6 and 129Sv inbred mice.
      In matching groups of CD-1 mice fed a diet containing 1% cholesterol for 21 days,
      hepatic cholesterol levels increased much more in the females (from 2.4 to 9.1
      mg/g) than in the males (from 2. 1 to 5.2 mg/g). This occurred even though the
      level of stimulation of cholesterol 7-hydroxylase activity in the females (79%)
      exceeded that in the males (55%), as did the magnitude of the increase in fecal
      bile acid excretion (females: 262% vs. males: 218%). However, in both sexes, bile
      acid pool size expanded only modestly and by a comparable degree (females: 19%
      vs. males: 26%) so that in the cholesterol-fed groups, the pool remained
      substantially larger in the females than in the males (102.3 vs. 67.6
      micromol/100 g body weight). Together, these data demonstrate that while male and
      female CD-1 mice do not differ qualitatively in the way cholesterol feeding
      changes their bile acid metabolism, the inherently larger bile acid pool in the
      female likely facilitates the delivery of significantly more dietary cholesterol
      to the liver than is the case in males, thereby resulting in higher steady-state
      hepatic cholesterol levels.

PMID- 9755248
TI  - Alpha3beta1-integrin as a critical mediator of the hepatic differentiation
      response to the extracellular matrix.
AB  - The extracellular matrix (ECM) promotes the differentiation of many cell types,
      and ECM remodeling in the liver has been implicated in embryonic development,
      tissue injury, and oncogenesis. Integrins are heterodimeric ECM receptors that
      play critical roles in transducing the composition of the ECM in the cell
      environment. We previously showed that mouse H2.35 cells, a conditionally
      transformed, liver-derived cell line, assume a more differentiated hepatocyte
      morphology and enhanced liver-specific gene expression when the cells are
      cultured on gelatinous ECM substrata. Here we show that H2. 35 cells express
      relatively high levels of alpha3beta1-integrins, similar to that previously shown
      for immature hepatocytes, transformed hepatocytes, and biliary cells. However,
      the cell morphological responses that depend on alpha3beta1-integrin have not
      been defined. We found that transfecting H2.35 cells with antisense RNA construct
      directed to alpha3-subunit messenger RNA perturbs the initial cell attachment to
      laminin and collagen, and strongly inhibits cell morphological, proliferative,
      and gene expression responses to a collagen gel substratum. In situ hybridization
      to mouse embryo tissues demonstrates the presence of alpha3-subunit messenger
      RNAs in newly formed hepatocytes. We suggest that alpha3beta1-integrins are
      important for immature and transformed hepatocytes to respond morphologically to
      the extracellular matrix.

PMID- 9755249
TI  - Hepatic iron overload in patients with chronic viral hepatitis: role of HFE gene
      mutations.
AB  - Mild to moderate hepatic iron overload is frequent in patients with chronic viral
      hepatitis (CH). We evaluated the role of hemochromatosis (HFE) gene mutations and
      other acquired factors in the development of iron overload in these patients. We
      studied 110 patients with chronic B or C viral hepatitis (31 women, 79 men),
      including 20 with cirrhosis, and 139 controls. Hepatic iron was evaluated by
      semiquantitative analysis in all the patients, and hepatic iron concentration
      (HIC) was determined in 97 of them (26 women, 71 men). C282Y and H63D mutations
      were sought in all the subjects by a polymerase chain reaction-restriction assay.
      The frequency of HFE genotypes and alleles did not differ in patients and
      controls. No relation was detected between hepatic iron stores and HFE gene
      mutations in women. In men, all C282Y heterozygotes had iron overload, and the
      H63D mutation was significantly more frequent in patients with more marked
      hepatic siderosis than in those with mild or no siderosis (P = .0039) and in
      controls (P = .0008). Heavy alcohol intake and hepatic cirrhosis were also
      associated with increased hepatic iron stores in the men. In the 71 men in whom
      HIC was measured, multiple regression analysis showed that this variable was
      related independently only to alcohol intake and HFE gene mutations. We suggest
      that in patients with CH, iron accumulates in the liver as the result of an
      interplay between genetic and acquired factors, and that increased liver iron
      stores may influence progression toward liver fibrosis.

PMID- 9755250
TI  - Effect of interferon therapy on hepatitis C virus RNA in whole blood, plasma, and
      peripheral blood mononuclear cells.
AB  - Fifty-two patients with chronic hepatitis C virus (HCV) infection were treated
      with standard doses of interferon alfa-2b. During treatment, HCV RNA detection
      was studied in samples of whole blood (WB), plasma (Pl), and peripheral blood
      mononuclear cells (PBMCs). Individuals were classified as sustained responders
      (SRs), complete responders with relapse (CRs), partial responders (PRs), or
      nonresponders (NRs) according to normalization of serum alanine transaminase
      (ALT) during treatment and follow-up. Before treatment, 100% of WB samples and
      more than 95% of Pl and PBMC samples were positive for HCV RNA. During treatment,
      there was progressive clearance of HCV RNA from Pl and PBMCs in SRs and CRs, but
      CRs had significantly more positive WB samples during and following treatment (P
      <.0001). At 6 months, only 10% of CR patients were positive by Pl assay, but 50%
      were positive by WB assay (P <.01). In the PR group, all WB samples remained
      positive throughout treatment, although 25% to 40% of PBMC and Pl samples became
      negative for HCV RNA during the first 2 months of therapy (WB > Pl or PBMC; P <
      .001). However, at later times during treatment most Pl and PBMC samples in the
      PR group were positive. Samples from the NR group showed no clearance of HCV RNA
      from WB, Pl, or PBMC fractions. These data document the increased sensitivity of
      WB assays for detecting HCV RNA in the peripheral blood of patients during
      interferon therapy. Furthermore, our findings suggest that WB analysis of HCV RNA
      may be a useful parameter to monitor in determining the end point of interferon
      therapy.

PMID- 9755251
TI  - High titers of antibodies inhibiting the binding of envelope to human cells
      correlate with natural resolution of chronic hepatitis C.
AB  - Most cases of hepatitis C virus (HCV) infection result in chronic disease;
      however, a very small fraction of patients naturally clear the virus and resolve
      chronic hepatitis. In an attempt to correlate immune response with chronic
      disease resolution, we compared the antibody response in patients with different
      outcomes of the infection. Antibody responses to HCV structural proteins were
      assessed in 34 patients originally diagnosed with acute hepatitis. Five cases
      resolved acute infection, 22 developed chronic hepatitis, and 7 naturally
      resolved chronic hepatitis C. To estimate HCV neutralizing antibodies we used the
      neutralization of binding (NOB) assay, which evaluates inhibition of the envelope
      2 protein binding to human cells. Enzyme-linked immunosorbent assay was used for
      the quantitative assessment of serum antibodies. The presence of HCV RNA was
      ascertained by reverse transcription-polymerase chain reaction. In 6 of 7
      patients naturally recovered from chronic hepatitis C, the emergence and the
      persistence (for more than 3 months) of high serum titers (>1/600) of NOB
      antibodies coincided with virus clearance and clinical resolution of hepatitis.
      NOB antibody activity was observed in only 2 of 5 patients recovered from acute
      hepatitis C. Chronic patients who did not show any resolution during the course
      of the study developed low or no NOB antibodies. Because of the correlation
      between prolonged high NOB titers and natural resolution of chronic hepatitis C,
      vaccination or passive immunization aimed at high titers of NOB antibodies may be
      valuable new therapeutic approaches for chronic hepatitis C.

PMID- 9755252
TI  - 10-Year follow-up after interferon-alpha therapy for chronic hepatitis C.
AB  - Sustained responses to interferon-alpha occur in 10% to 25% of patients with
      chronic hepatitis C, but the long-term outcome is not well defined. We evaluated
      the long-term clinical, histological, and virological outcomes of 10 patients
      with chronic hepatitis C who were treated between 1984 and 1987 with interferon
      alpha-2b for 52 +/- 6 weeks (total doses of 492 +/- 116 MU). Before therapy, all
      10 had hepatitis C virus (HCV) RNA, elevations of serum aminotransferases, and
      chronic hepatitis with fibrosis on liver biopsy. Clinical follow up was 6 to 13
      years, and liver biopsies were done 5 to 11 years after initiation of therapy.
      HCV RNA was assayed by qualitative and quantitative reverse transcriptase
      polymerase chain reaction assays. Among 5 patients who had a 6-month sustained
      response after therapy, all remained HCV RNA negative, and at last follow-up, 4
      had normal and 1 minimally elevated serum aminotransferase levels. Liver biopsy
      specimens were nonreactive for HCV RNA, and all the patients showed improvements
      in both inflammation and fibrosis and were either normal or had mild, nonspecific
      inflammatory changes. Among 5 patients without a sustained response, all
      continued to have HCV RNA in serum and persistent or intermittent
      aminotransferase elevations. Liver biopsy specimens showed little or no change in
      necrosis and inflammation; all except 1 patient had progression of fibrosis
      scores or cirrhosis. All 5 patients had symptoms of chronic hepatitis, 1
      underwent liver transplantation, and another had progressive hepatic
      decompensation. In conclusion, patients with a 6-month posttreatment virological
      response have a favorable long-term clinical and histological outcome.

PMID- 9755253
TI  - Ultrastructural analysis of hepatitis B virus in HepG2-transfected cells with
      special emphasis on subviral filament morphogenesis.
AB  - The intracellular accumulation of empty hepatitis B virus (HBV) particles of
      filamentous shape leads to a direct cytopathic effect in so-called ground-glass
      hepatocytes. The aim of this study was to investigate how these filaments can be
      structurally formed at the cellular level. By electron microscopy, we reexamined
      the HBV-producer HepG2T-14 cells, which have been described as producing a
      substantial amount of empty HBV filaments compared with the other forms of HBV
      particles. Examination of ultrathin sections of HepG2T14 cells revealed the
      presence of HBV virions and filaments at the periphery of extremely large
      intracellular cisternae, probably related to a pre-Golgi compartment. Very long
      filaments appeared to be formed by a tubular budding of a long portion of the
      cisterna membrane. This phenomenon may be identical to that observed in the
      hepatocytes of HBV chronic carriers, in which the inability of the infected cell
      to export long HBV filamentous particles through the cellular secretion pathway
      seems to be at the origin of a direct cytopathic effect.

PMID- 9755254
TI  - Hepatitis B virus replication in human HepG2 cells mediated by hepatitis B virus
      recombinant baculovirus.
AB  - A novel transient mechanism for studying hepatitis B virus (HBV) gene expression
      and replication using recombinant HBV baculovirus to deliver the HBV genome to
      HepG2 cells was generated. In HBV baculovirus infected HepG2 cells, HBV
      transcripts, and intracellular and secreted HBV antigens are produced;
      replication occurs as evidenced by the presence of high levels of intracellular
      replicative intermediates and protected HBV DNA in the medium. Density-gradient
      analysis of extracellular HBV DNA indicated that the DNA was contained
      predominantly in enveloped HBV virions. Covalently closed circular (CCC) DNA is
      present indicating that, in this system, HBV core particles are capable of
      delivering newly synthesized HBV genomes back into the nuclei of infected cells.
      HBV gene expression is driven exclusively from endogenous promoters. Levels of
      HBV gene expression and replication can be achieved in HBV baculovirus-infected
      HepG2 cells which far exceed levels found in HepG2 2.2.15 cells. HBV baculovirus
      infection of HepG2 cells lends itself readily to experimental manipulation as
      follows: 1) HBV expression can be initiated any time relative to seeding of HepG2
      cells; 2) levels of HBV replication can be regulated over a wide range simply by
      changing the baculovirus multiplicity of infection; 3) HBV replication is readily
      detectable by one day post infection with HBV baculovirus and persists at least
      through day eleven post infection; and (4) the transient nature of the infection
      can be extended and/or enhanced by superinfecting the cultures. We conclude that
      infection of HepG2 cells by HBV recombinant baculovirus represents a simple to
      use and highly flexible system for studying the effects of antivirals and/or
      cytokines on HBV production and for understanding HBV replication and
      pathogenesis at the molecular level.

PMID- 9755256
TI  - Management of ectopic varices.

PMID- 9755257
TI  - New perspectives on the pathogenesis of Cryptosporidium biliary disease.

PMID- 9755255
TI  - Mutations in the interferon-sensitivity determining region of hepatitis C virus
      and transcriptional activity of the nonstructural region 5A protein.
AB  - Amino acid (aa) mutations in the interferon-sensitivity determining region (ISDR)
      (aa position 237-276 of the nonstructural region 5A [NS5A] protein consisting of
      447 amino acids) of hepatitis C virus (HCV) are related to increased interferon
      sensitivity and low viral load, but its mechanism has not been clarified.
      Recently, the NS5A protein has been reported to have a transcriptional activation
      function, like other viral transactivator proteins known to repress interferon
      induced gene expression, and the ISDR overlaps one of the acidic amino acid
      regions, putative domains conferring this activity. In the present study, we
      investigated the transcriptional activation function of the ISDR itself and the
      effect of amino acid mutations in the ISDR on this activity. The full-length or
      truncated NS5A cDNA with different ISDR sequences was cloned into a yeast or
      mammalian expression vector to form a fusion protein consisting of the GAL4 DNA
      binding domain (GAL4-DBD) and NS5A protein. Following transfection, the
      transcriptional activities of these constructs were determined using beta
      galactosidase (yeast) or chloramphenicol acetyltransferase (CAT) (mammalian cell)
      reporter gene expression under the control of GAL4 binding sites. In yeast, both
      the full-length sequence of NS5A-R (a clone with one aa mutation in the ISDR) and
      NS5A-S (a derivative of NS5A-R with six aa mutations in the ISDR) had no
      distinguishable transcriptional activity, whereas an amino-terminal deletion
      construct of NS5A-R (aa position 228-447) lacking 227 aa, showed remarkable
      activity with the relative value of 117.0 over that of the backbone vector. The
      same deletion mutant of NS5A-S produced five times higher activity with the
      relative value of 575.0, indicating that aa mutations in the ISDR profoundly
      affect this transcriptional activity. In a hepatoma cell line, HuH-7, the
      transcriptional activity was more prominent with a construct consisting of only
      the ISDR and short flanking sequences (aa 228-284) than larger deletion
      constructs of NS5A-R. Analysis using six different ISDR clones revealed that
      different mutations enhanced this activity to various extent compared with the
      wild-type ISDR. In particular, site-directed mutagenesis targeted to the aa
      position 252 showed that this aa residue had profound influence on the activity.
      These results suggest that the ISDR has a transcriptional activity, and it is
      enhanced by aa mutations that are also related to decreased viral load and
      increased interferon sensitivity. The possible association between
      transcriptional activation and interferon sensitivity or viral replication should
      be studied further.

PMID- 9755258
TI  - Hepatocellular carcinoma.

PMID- 9755259
TI  - A novel use of xylitol sugar in preventing acute otitis media.
AB  - BACKGROUND: Xylitol, a commonly used sweetener, is effective in preventing dental
      caries. As it inhibits the growth of pneumococci, we evaluated whether xylitol
      could be effective in preventing acute otitis media (AOM). DESIGN: Altogether,
      857 healthy children recruited from day care centers were randomized to one of
      five treatment groups to receive control syrup (n = 165), xylitol syrup (n =
      159), control chewing gum (n = 178), xylitol gum (n = 179), or xylitol lozenge (n
      = 176). The daily dose of xylitol varied from 8.4 g (chewing gum) to 10 g
      (syrup). The design was a 3-month randomized, controlled trial, blinded within
      the chewing gum and syrup groups. The occurrence of AOM each time the child
      showed any symptoms of respiratory infection was the main outcome. RESULTS:
      Although at least one event of AOM was experienced by 68 (41%) of the 165
      children who received control syrup, only 46 (29%) of the 159 children receiving
      xylitol syrup were affected, for a 30% decrease (95% confidence interval [CI]:
      4.6%-55.4%). Likewise, the occurrence of otitis decreased by 40% compared with
      control subjects in the children who received xylitol chewing gum (CI: 10.0%
      71.1%) and by 20% in the lozenge group (CI: -12.9%-51.4%). Thus, the occurrence
      of AOM during the follow-up period was significantly lower in those who received
      xylitol syrup or gum, and these children required antimicrobials less often than
      did controls. Xylitol was well tolerated. CONCLUSIONS: Xylitol sugar, when given
      in a syrup or chewing gum, was effective in preventing AOM and decreasing the
      need for antimicrobials.

PMID- 9755260
TI  - Selective head cooling in newborn infants after perinatal asphyxia: a safety
      study.
AB  - AIMS: To determine the practicality and safety of head cooling with mild or
      minimal systemic hypothermia in term neonates with moderate to severe hypoxic
      ischemic encephalopathy. METHODS: Study group infants >/=37 weeks' gestation, who
      had an umbilical artery pH </=7. 09 or Apgars </=6 at 5 minutes, plus evidence of
      encephalopathy. Infants with major congenital abnormalities were excluded. TRAIL
      DESIGN: Infants were randomized to either no cooling (controls; rectal
      temperature = 37.0 +/- 0.2 degreesC, n = 10) or sequentially, either minimal
      systemic cooling (rectal temperature = 36.3 +/- 0.2 degreesC, n = 6) or mild
      systemic cooling (rectal temperature = 35.7 +/- 0.2 degreesC, n = 6). Head
      cooling was accomplished by circulating water at 10 degreesC through a coil of
      tubing wrapped around the head for up to 72 hours. All infants were warmed by
      servo-controlled overhead heaters to maintain the allocated rectal temperature.
      The rectal, fontanelle, and nasopharyngeal temperatures were continuously
      monitored. RESULTS: From January 1996 to October 1997, 22 term infants were
      randomized from 2 to 5 hours after birth. All infants showed a metabolic acidosis
      at delivery, with similar umbilical artery pH in the control group (mean +/-
      standard deviation, 6.79 +/- 0.25), minimal cooling group (6.98 +/- 0.21), and
      mild cooling group (6.93 +/- 0.11), and depressed Apgar scores at 5 minutes in
      the control group (4.5 +/- 2), minimal cooling group, (4.7 +/- 2) and mild
      cooling group (6.0 +/- 1). In the mild-cooled infants, the nasopharyngeal
      temperature was 34.5 degreesC during cooling, 1.2 degreesC lower than the rectal
      temperature. This gradient narrowed to 0.5 degreesC after cooling was stopped. No
      adverse effects because of cooling were observed. No infants developed cardiac
      arrhythmias, hypotension, or bradycardia during cooling. Thrombocytopenia
      occurred in 2 out of 10 controls, 2 out of 6 minimal cooling infants, and 1 out
      of 6 mild cooling infants. Hypoglycemia (glucose <2.6 mM) was seen on at least
      one occasion in 2 out of 10 controls, 4 out of 6 minimal cooling infants, and 1
      out of 6 mild cooling infants. Acute renal failure occurred in all infants. The
      metabolic acidosis present in all infants at the time of enrollment into the
      study progressively resolved despite cooling, even in the mild hypothermia group.
      CONCLUSIONS: Mild selective head cooling combined with mild systemic hypothermia
      in term newborn infants after perinatal asphyxia is a safe and convenient method
      of quickly reducing cerebral temperature with an increased gradient between the
      surface of the scalp and core temperature. The safety of mild hypothermia with
      selective head cooling is in contrast with the historical evidence of adverse
      effects with greater depths of whole-body hypothermia. This safety study and the
      strong experimental evidence for improved cerebral outcome justify a multicenter
      trial of selective head cooling for neonatal encephalopathy in term infants.

PMID- 9755261
TI  - Declining severity adjusted mortality: evidence of improving neonatal intensive
      care.
AB  - OBJECTIVES: Declines in neonatal mortality have been attributed to neonatal
      intensive care. An alternative to the "better care" hypothesis is the "better
      babies" hypothesis; ie, very low birth weight infants are delivered less ill and
      therefore have better survival. DESIGN: We ascertained outcomes of all live
      births <1500 g in two prospective inception cohorts. We estimated mortality risk
      from birth weight and illness severity on admission and measured therapeutic
      intensity. We calculated logistic regression models to estimate the changing odds
      of mortality between cohorts. PATIENTS AND SETTING: Two cohorts in the same two
      hospitals, 5 years apart (1989-1990 and 1994-1995) (total n = 739). RESULTS:
      Neonatal intensive care unit mortality declined from 17.1% to 9.5%, and total
      mortality declined from 31.6% to 18.4%. Cohort 2 had lower risk (higher birth
      weight, gestational age, and Apgar scores and lower admission illness severity
      for newborns >/=750 g). Risk-adjusted mortality declined (odds ratio, 0.52;
      confidence interval, 0.29-0. 96). One third of the decline was attributable to
      "better babies" and two thirds to "better care." Use of surfactant, mechanical
      ventilation, and pressors became more aggressive, but decreases in monitoring,
      procedures, and transfusions resulted in little change in therapeutic intensity.
      CONCLUSIONS: Mortality decreased nearly 50% for infants <1500 g in 5 years. One
      third of this decline is attributable to improved condition on admission that
      reflects improving obstetric and delivery room care. Two thirds of the decline is
      attributable to more effective newborn intensive care, which was associated with
      greater aggressiveness of respiratory and cardiovascular treatments. Attribution
      of improved birth weight specific mortality solely to neonatal intensive care may
      underestimate the contribution of high-risk obstetric care in providing "better
      babies."

PMID- 9755262
TI  - Prospective study of persistence and excretion of human herpesvirus-6 in patients
      with exanthem subitum and their parents.
AB  - OBJECTIVE: To elucidate persistence of human herpesvirus-6 (HHV-6) in the blood
      and excretion of the virus into several body fluids of patients with exanthem
      subitum (ES), and to examine serologic and virologic findings of the parents
      caring for the patients in the family setting. MATERIALS AND METHODS: During a 15
      month period, 20 infants from 20 families (11 boys and 9 girls; mean age, 7.7
      months; range, 4-11 months) with primary HHV-6 infection and a typical clinical
      course of ES, and 15 parents from the 20 families (2 males and 13 females; mean
      age, 28.2 years; range, 21-34 years) were enrolled in the study and examined
      clinically and virologically. Primary infection with HHV-6 was confirmed by
      isolation of the virus from peripheral blood mononuclear cells (MNCs), and
      seroconversion or a significant increase in the antibody titers to HHV-6 by a
      neutralization test. Viral persistence or excretion was examined by amplifying
      the viral deoxyribonucleic acid (DNA) in serially collected peripheral blood
      MNCs, plasma, saliva, stool, and urine samples with a nested polymerase chain
      reaction method. Data on saliva from the parents were compared with those of 21
      age-matched controls. RESULTS: Twenty infants with virologically confirmed ES had
      HHV-6 DNA in MNCs persistently during and after the disease but in plasma only in
      the first 5 days of ES. The viral DNA was also detected persistently or
      intermittently in saliva and stool during and after the disease but rarely in
      urine. On the other hand, the 15 parents examined of the 20 infants had no HHV-6
      viremia nor viral DNA in peripheral blood MNCs and plasma except 1, but half of
      them excreted viral DNA in saliva during and after ES. The frequency of excretion
      of viral DNA into saliva was not significantly different from that of 21 control
      parents. Only 1 of the 15 showed a fourfold increase in antibody titers to HHV-6
      after possible exposure from their children. CONCLUSIONS: After systemic
      replication of HHV-6 in the blood of patients with ES during the first 5 days of
      the disease, the virus is excreted into saliva and stool persistently or
      intermittently but rarely into urine. The presence of HHV-6 DNA in plasma
      suggested active infection with the virus. Excretion of the virus into the saliva
      of infants with ES and their parents suggests the source and transmission route
      of infection with HHV-6.

PMID- 9755263
TI  - Lyme arthritis in children: clinical epidemiology and long-term outcomes.
AB  - OBJECTIVE: Although Lyme disease has become a relatively common cause of
      arthritis among children in areas of the country in which the disease is endemic,
      little information is available about the clinical epidemiology and long-term
      outcomes of children with Lyme arthritis. We conducted a long-term follow-up
      study to determine the clinical epidemiology of Lyme arthritis in children as
      well as their long-term outcomes. PATIENTS AND METHODS: All children seen between
      1982 and 1991 at the Pediatric Rheumatology Clinic at Newington Children's
      Hospital (Newington, CT) with an initial diagnosis of Lyme disease were
      identified. Medical records were reviewed and structured telephone interviews
      were conducted to obtain demographic, clinical, and follow-up data. RESULTS: A
      total of 90 children (63% boys) with a mean age of 8.3 years (range, 1.8-16
      years) at the time of diagnosis of Lyme arthritis were evaluated. Lyme arthritis
      was preceded by early Lyme disease in 23 (26%) of the children; however, only 8
      (35%) of these children had been treated with appropriate antimicrobial therapy
      at that early stage. Ninety percent of the children had arthritis of at least one
      knee, while small joints were rarely involved. For the 31 children who underwent
      arthrocentesis, the mean white blood cell count in the synovial fluid was 38 000
      cells/mm3 (range, 7000-99 000 cells/mm3) with predominantly neutrophils. For the
      79 children for whom an erythrocyte sedimentation rate was determined, the
      highest level for 61 (77%) was >20 mm/h and for 36 (46%) was >50 mm/h.
      Antimicrobial therapy was initiated 2 days to 5.5 years (median, 2 months) after
      the onset of symptoms. However, 5 of the children were never treated with
      antimicrobials. Fifty-one percent of the patients had a single episode of
      arthritis, while 49% reported recurrent episodes of arthritis over a period of 1
      week to 8 years (median, 6 months). Two children (2%) developed chronic arthritis
      and underwent arthroscopic synovectomy. At the time of the telephone follow-up
      evaluation, performed 2 to 12 years (median, 7 years) after the onset of the Lyme
      arthritis, 4 children had ongoing musculoskeletal complaints that resulted in
      mild to moderate impairment of school or sports activities, but none of the
      children had evidence of active arthritis. CONCLUSION: The results of this
      investigation suggest that the prognosis for children with Lyme arthritis who are
      treated with appropriate antimicrobial therapy is excellent.

PMID- 9755264
TI  - The effect of investigator compliance (observer bias) on calculated efficacy in a
      pertussis vaccine trial.
AB  - BACKGROUND: In the course of a large pertussis vaccine efficacy trial we realized
      that investigator compliance could have a major impact on calculated vaccine
      efficacy. DESIGN: In our pertussis vaccine efficacy trial, the study
      investigators were to monitor illness in study families by telephone every 2
      weeks. If a cough illness of >/=7 days duration was noted, the study child was to
      be evaluated. If the cough illness persisted for >/=14 days, the child was to be
      referred to a central investigator. For this report we analyzed study physician
      evaluation rates and rates of referral to the central investigators. Physician
      practices were separated into three compliance categories: high, intermediate,
      and low. We analyzed vaccine efficacy of an acellular pertussis component DTP
      vaccine (DTaP) and a whole cell pertussis component DTP vaccine (DTP) by
      compliance category. Bordetella pertussis infection was documented by culture of
      the organism in the study child or in a household contact or by a significant
      antibody response to pertussis toxin determined by enzyme-linked immunosorbent
      assay. RESULTS: Using a clinical case definition that included both mild and
      typical pertussis (cough illness >/=7 days duration) efficacy of DTaP vaccine was
      40% (95% confidence interval [CI] = -3-65) in the high compliance category and
      78% (95% CI = 65-86) and 75% (95% CI = 53-87) in the intermediate and low
      compliance groups, respectively. Similar, but less marked, differences in
      efficacy were noted with DTP vaccine recipients. Using a clinical case definition
      that required >/=21 days of cough with paroxysms, whoop, or vomiting (typical
      pertussis) the efficacy of DTaP vaccine was 69% (95% CI = 41-83) in the high
      compliance category and 86% (95% CI = 76-92) and 84% (95% CI = 64-93) in the
      intermediate and low compliance groups, respectively. In contrast, the efficacy
      of DTP vaccine did not vary by compliance category using this case definition.
      The attack rate in children vaccinated with diphtheria and tetanus toxoids
      vaccine (DT) was twofold less in low compliance physician practices when compared
      with the rates in high and intermediate groups. The DT/DTaP and DT/DTP fold
      change differences were less in the high compliance group compared with the
      intermediate and low compliance groups. CONCLUSIONS: Our data suggest that
      observer compliance (observer bias), can significantly inflate calculated vaccine
      efficacy. It is likely that all recently completed efficacy trials have been
      effected by this type of observer bias and all vaccines have considerably less
      efficacy against mild disease than published data suggest.

PMID- 9755265
TI  - Dietary sources of nutrients among US children, 1989-1991.
AB  - OBJECTIVE: To identify major food sources of nutrients and dietary constituents
      for US children. METHODS: Twenty-four-hour dietary recalls were collected from a
      nationally representative sample of children age 2 to 18 years (n = 4008) from
      the US Department of Agriculture's 1989-1991 Continuing Survey of Food Intakes by
      Individuals. For each of 16 dietary constituents, the contribution of each of 113
      food groups was obtained by summing the amount provided by the food group for all
      individuals and dividing by total intake from all food groups for all
      individuals. RESULTS: Milk, yeast bread, cakes/cookies/quick breads/donuts, beef,
      and cheese are among the top 10 sources of energy, fat, and protein. Many of the
      top 10 sources of carbohydrate (yeast bread, soft drinks/sodas, milk, ready-to
      eat cereal, cakes/cookies/quick breads/donuts, sugars/syrups/jams, fruit drinks,
      pasta, white potatoes); protein (poultry, ready-to-eat cereal, pasta); and fat
      (potato chips/corn chips/popcorn) also contributed >2% each to energy intakes.
      Ready-to-eat cereal is among the top contributors to folate, vitamin A, vitamin
      C, iron, and zinc intakes. Fruit drinks, containing little juice, contribute
      approximately 14% of total vitamin C intakes. CONCLUSIONS: Fortified foods are
      influential contributors to many vitamins and minerals. Low nutrient-dense foods
      are major contributors to energy, fats, and carbohydrate. This compromises
      intakes of more nutritious foods and may impede compliance with current dietary
      guidance.

PMID- 9755266
TI  - Syncope recurrence in children: relation to tilt-test results.
AB  - OBJECTIVES: To examine the intermediate-term outcome of children with syncope and
      its relationship to tilt test. DESIGN: This was a retrospective study of 45
      children. In 20, the tilt test was negative. Follow-up with respect to the
      recurrence of syncope was obtained via chart review, a mailed questionnaire, or
      telephone interview. RESULTS: Follow-up data were available on 15 children whose
      tilt test was negative and on all 25 tilt-test positive children. Recurrent
      syncope was significantly greater in the positive-tilt children (13 of 25) than
      the negative-tilt children (2 of 15). There was no difference between the syncope
      free group and the recurrent syncope group or between the tilt-positive and tilt
      negative groups with respect to age at initial syncope, duration of symptoms, age
      at tilt test, and duration of follow-up. Children with a positive tilt test and
      those with recurrent syncope had more syncopal episodes before their evaluation
      than either the group with a negative tilt test or the group with no recurrent
      syncope, respectively. CONCLUSIONS: Syncope may recur after either a negative or
      a positive tilt test. The recurrence rate, however, is higher for the tilt
      positive children.

PMID- 9755267
TI  - Early clinical markers for the development of bronchopulmonary dysplasia: soluble
      E-Selectin and ICAM-1.
AB  - OBJECTIVE: To test the hypothesis that in infants born at </=29 weeks' gestation
      soluble adhesion molecule concentrations would be higher in the first week of
      life in infants that subsequently develop bronchopulmonary dysplasia than in
      infants that do not. DESIGN AND METHODS: In cord blood and on days of life 1, 3,
      and 7, we measured serum concentrations of soluble P-Selectin, E-Selectin, and
      intercellular adhesion molecule-1 in samples obtained from infants </=29 weeks'
      gestational age. At 1 month of age we assessed the infants' clinical courses to
      determine whether the infants met the criteria for the diagnosis of
      bronchopulmonary dysplasia (BPD) and evaluated the infants' radiographic studies
      to stage the level of BPD. On discharge, the duration of oxygen therapy, the
      requirement for home oxygen therapy, and length of hospital stay were determined.
      RESULTS: Concentrations of soluble P-Selectin were greatest in cord blood samples
      obtained from all infants and were markedly reduced on day of life 1, regardless
      of the subsequent development of BPD. In serum samples obtained from cord blood
      and on days of life 1 and 3, soluble E-Selectin levels were higher in infants
      that developed BPD than in infants that did not develop BPD. In addition, the
      highest concentrations of soluble E-Selectin in serum samples from cord blood and
      on day of life 1 were associated with the development of stage 3 or 4 BPD.
      Soluble intercellular adhesion molecule-1 concentrations were higher on days of
      life 3 and 7 in the infants that went on to develop BPD than in those that did
      not. CONCLUSIONS: Because neutrophil attachment to endothelial cell adhesion
      molecules is a key event in the initiation of an inflammatory response, the
      association of higher early concentrations of soluble E-Selectin with the
      development of BPD suggests that E-Selectin may play a key role in the
      pathogenesis of lung inflammation and the development of BPD. This association
      also suggests that inflammatory events or effects leading to inflammatory
      responses occurring in the prenatal and/or very early perinatal periods
      contribute significantly to the pathogenesis of BPD.

PMID- 9755268
TI  - Clinically significant upper gastrointestinal bleeding acquired in a pediatric
      intensive care unit: a prospective study.
AB  - OBJECTIVES: To determine the incidence, risk factors, and complications
      associated with or attributable to clinically significant upper gastrointestinal
      (GI) bleeding acquired in a pediatric intensive care unit (ICU). METHODS:
      Prospective, descriptive epidemiologic study in a multidisciplinary pediatric ICU
      of a tertiary-care university hospital. Upper GI bleeding was considered to be
      present if hematemesis occurred or blood was present in the gastric tube. An
      upper GI bleed was qualified as clinically significant if two or three reviewers
      independently assessed that at least one of the six complications considered for
      analysis was attributable to the upper GI bleed. RESULTS: A cohort of 1114
      consecutive admissions was enrolled; 108 (9.7%) were excluded mostly (37.0%)
      because they already had an upper GI bleed at entry to the pediatric ICU. The
      final sample included 1006 admissions (881 patients); 103 upper GI bleeds (10.2%)
      were diagnosed, including 16 clinically significant upper GI bleeds (1. 6%).
      Complications attributed to an upper GI bleed included: decreased hemoglobin
      concentration (10 cases), transfusion (10), hypotension (3), and surgery (1).
      Three independent risk factors for clinically significant upper GI bleeding were
      retained by multivariate analysis: respiratory failure, coagulopathy, and
      pediatric risk of mortality score >/=10. Nine of the 16 cases (56. 3%) with
      clinically significant upper GI bleeding had three risk factors, 14 (87.5%) had
      two, and 1 (6.3%) had none. CONCLUSIONS: Clinically significant upper GI bleeds
      are rare in critically ill children. Prophylaxis to prevent them may be limited
      to patients who present with at least two risk factors.

PMID- 9755269
TI  - Evaluation of vaginal infections in adolescent women: can it be done without a
      speculum?
AB  - OBJECTIVE: Given that highly sensitive urine-based nucleic acid amplification
      tests may eliminate the need for speculum exam to diagnose gonorrhea and
      chlamydia cervicitis, we sought to determine if vaginal infections could be
      diagnosed without using a speculum. METHODS: Matched pairs of vaginal specimens
      were collected from participants before and during speculum exam for diagnosis of
      trichomoniasis, bacterial vaginosis, and vulvovaginal candidiasis. Females age 12
      to 22 years presenting to the Johns Hopkins adolescent primary care clinics who
      required a pelvic examination were eligible to participate. A convenience sample
      of 686 patients was recruited between July 1995 and August 1996. Paired vaginal
      specimens were evaluated with blinded microscopic evaluation. Analysis consisted
      of: 1) comparison of collection method sensitivities; and 2) assessment of
      proportions of infections detected by one method that were also detected by the
      other method. RESULTS: Sensitivities of speculum and nonspeculum collection
      methods were 75% and 77% (difference = -2%; 95% confidence interval, -11%, 7%)
      for trichomoniasis, 64% and 68% (difference = -4% [-10%, 3%]) for bacterial
      vaginosis, and 85% and 80% (difference = 5% [-12%, 22%]) for vulvovaginal
      candidiasis. The speculum method identified 88% (trichomoniasis), 90% (bacterial
      vaginosis), and 81% (vulvovaginal candidiasis) of infections detected by the
      nonspeculum method. The nonspeculum method identified 91% (trichomoniasis), 95%
      (bacterial vaginosis), and 76% (vulvovaginal candidiasis) of infections detected
      by the speculum method. CONCLUSIONS: Vaginal infections can be adequately
      diagnosed without a speculum. Once urine-based diagnosis of gonorrhea and
      chlamydia becomes well established, it may be possible to perform evaluations for
      uncomplicated genitourinary complaints without using a speculum.

PMID- 9755270
TI  - Prenatal cocaine exposure and child behavior.
AB  - OBJECTIVE: The aim of this study was to evaluate previous teacher reports that
      children exposed to cocaine prenatally have more problem behaviors. METHODS: A
      historical, prospective design was used. Maternal subjects (n = 116) of 6-year
      old singleton, term (>/=36 weeks) children, and the children's first-grade
      teachers (n = 102) agreed to participate. The child's first-grade teacher,
      blinded to study design and exposure status, rated the child's behavior with the
      Conners' Teacher Rating Scales (CTRS) and an investigator-developed scale, the
      Problem Behavior Scale (PROBS 14), measuring behaviors reported by educators to
      be specific to cocaine exposure. Mothers were interviewed by telephone regarding
      demographic and socioeconomic factors. RESULTS: Although the cocaine-exposed
      group had higher (more problem behaviors) for each of the CTRS subscales, the
      overall multivariate analysis of variance for the CTRS was not significant.
      Children exposed to cocaine prenatally had higher scores (more problem behaviors)
      for 11 of the 14 PROBS items and the overall multivariate analysis of variance
      relating prenatal cocaine exposure to the PROBS was significant (Wilkes' lambda
      =.775), even after controlling for gender and prenatal exposure to alcohol and
      cigarettes. CONCLUSIONS: This pilot study supports that teachers blinded to
      exposure status of early elementary students did rate the cocaine-exposed group
      as demonstrating significantly more problem behaviors than control children.
      Although an important first step, postnatal factors that also may influence
      behavior were not evaluated; hence, causation is not addressed.

PMID- 9755271
TI  - Catch-up growth in children treated with home enteral nutrition.
AB  - OBJECTIVE: This study was designed to determine the effect of home enteral
      nutrition on the outcomes of growth and the relationship between growth and
      entrance anthropometric criteria. METHODS: We reviewed the medical records of 78
      consecutive children (median age, 20 months) who were enrolled in the home
      enteral feeding program at the Alberta Children's Hospital (Calgary, Alberta,
      Canada) between 1993 and 1995. Weights, heights, and weight-for-heights were
      expressed as Z scores, using the Centers for Disease Control and Prevention
      anthropometric growth curve software. To evaluate growth outcome, the total group
      was further subdivided using anthropometric criteria into appropriate, wasted, or
      stunted at the time of entry to the program. In a subgroup of 36 children on whom
      anthropometric data was available for a median length of 5.7 months, Z scores
      were compared at 3 points in time: before entry, at time of entry, and last
      follow-up. RESULTS: Patients were classified into five main groups: 11 (14%) had
      pulmonary disease, 26 (33%) had a gastrointestinal disorder, 21 (27%) had
      congenital defects, 10 (13%) had a neurologic disorder, and the remaining 10
      (13%) had a variety of other illnesses, including malignancies and metabolic
      disorders. Patients were on the program for a median duration of 8.9 months. It
      was found that during the period of support within the program, enteral feeding
      was successful in improving weight-for-age Z scores by 0.42 standard deviations
      but the effect on height-for-age Z scores and weight-for-height Z scores did not
      reach significance for this population. The subgroup of 36 children on whom
      longitudinal anthropometric data was available before entering the program was
      found to have had a significant drop in weight Z scores between the time before
      program entry (median length of time, 5.7 months) and the time of program entry,
      which indicates that these children were falling off the growth curve before
      commencing enteral feeding. To evaluate growth outcome, the total group was
      further subdivided using anthropometric criteria into appropriate, wasted, or
      stunted at the time of entry to the program. In the group of appropriate growth
      patients, while in the program, 50% had catch-up growth for weight (positive
      change in Z scores) and 33% for height. In the wasted patients, 92% improved
      their weight percentile and 75% their height percentile. In the stunted group,
      71% had catch-up growth for weight and 74% for height. CONCLUSION: We concluded
      that the enteral feeding program was able to promote catch-up growth or maintain
      growth along percentiles in the majority of children.

PMID- 9755274
TI  - Bisphosphonates for treatment of childhood hypercalcemia.
AB  - Most clinicians only have a limited experience in treating childhood
      hypercalcemia with bisphosphonates. We report our experience in the use of
      intravenous and oral bisphosphonates in a 5-year-old with hypercalcemia secondary
      to acute lymphocytic leukemia, a 16-year-old with immobilization hypercalcemia,
      and a 14-year-old with chronic hypercalcemia of unknown cause. Single infusions
      of 0.5 mg/kg and 1 mg/kg of intravenous pamidronate were administered over 4
      hours. No adverse reactions were observed except for hypocalcemia. A dose between
      10 and 20 mg of oral alendronate was successfully used to maintain normocalcemia
      in the patient with chronic hypercalcemia. In our experience, the administration
      of bisphosphonates has enabled us to achieve normocalcemia in all cases, and in
      all cases there were no significant side effects. Long-term potential side
      effects from their use in children during the active phase of growth remain
      unknown.

PMID- 9755273
TI  - Pertussis encephalopathy with high cerebrospinal fluid antibody titers to
      pertussis toxin and filamentous hemagglutinin.
AB  - A 7-year-old unimmunized girl with pertussis presented with respiratory failure
      and electroencephalographic evidence of an encephalopathy. The cerebrospinal
      fluid (CSF)/serum ratio of antibodies to pertussis toxin and filamentous
      hemagglutinin were 11- and ninefold higher than the CSF/serum ratio of total
      immunoglobulin G. The CSF/serum ratio of albumin was normal. These findings
      indicate production of antibodies in the central nervous system to Bordetella
      pertussis antigens and imply, therefore, that the pertussis encephalopathy in
      this girl was associated with the entry of pertussis antigens into the central
      nervous system.

PMID- 9755272
TI  - Comparison of fentanyl/midazolam with ketamine/midazolam for pediatric orthopedic
      emergencies.
AB  - OBJECTIVE: Emergency management of pediatric fractures and dislocations requires
      effective analgesia, yet children's pain is often undertreated. We compared the
      safety and efficacy of fentanyl- versus ketamine- based protocols. METHODOLOGY:
      Patients 5 to 15 years of age needing emergency fracture or joint reduction (FR)
      were randomized to receive intravenous midazolam plus either fentanyl (F/M) or
      ketamine (K/M). Measures of efficacy were observational distress scores and self-
      and parental-report. Measures of safety were frequency of abnormalities in and
      need for support of cardiopulmonary function and other adverse effects. RESULTS:
      During FR, K/M subjects (n = 130) had lower distress scores and parental ratings
      of pain and anxiety than did F/M subjects (n = 130). Although both regimens
      equally facilitated reductions, deep sedation, and procedural amnesia,
      orthopedists favored K/M. Recovery was 14 minutes longer for K/M. Fewer K/M
      subjects had hypoxia (6% vs 25%), needed breathing cues (1% vs 12%), or required
      oxygen (10% vs 20%) than did F/M subjects. Two K/M subjects required assisted
      ventilation briefly. More K/M subjects vomited. Adverse emergence reactions were
      rare but equivalent between regimens. CONCLUSIONS: During emergency pediatric
      orthopedic procedures, K/M is more effective than F/M for pain and anxiety
      relief. Respiratory complications occurred less frequently with K/M, but
      respiratory support may be needed with either regimen. Both regimens facilitate
      reduction, produce amnesia, and rarely cause emergence delirium. Vomiting is more
      frequent and recovery more prolonged with K/M.

PMID- 9755275
TI  - Principles of child health care financing. American Academy of Pediatrics.
      Committee on Child Health Financing.
AB  - Child health care financing must maximize access to and ensure quality
      comprehensive child and maternal care. This policy statement replaces the 1993
      policy statement, "Principles of Child Health Care Financing." Changes reflect
      new state and federal legislation that affect child health care financing. The
      principles outlined in the policy statement will be used to evaluate the changing
      structure of health care financing.

PMID- 9755276
TI  - Issues in the application of the resource-based relative value scale system to
      pediatrics: a subject review. American Academy of Pediatrics. Resource-Based
      Relative Value Scale Project Advisory Committee.
AB  - In today's rapidly changing health care environment, it is crucial to understand
      the genesis and concepts of the Medicare Resource-based Relative Value Scale
      (RBRVS) physician fee schedule. Many third-party payers, including state Medicaid
      programs, Blue Cross-Blue Shield agencies, and managed care organizations are
      using variations of the Medicare RBRVS to determine physician reimbursement and
      capitation rates. Because the RBRVS fee schedule was originally created for
      Medicare only, pediatric-specific Current Procedural Terminology codes and
      pediatric practice expense issues were not included. The American Academy of
      Pediatrics agrees with the use of the Current Procedural Terminology codes and
      the RBRVS physician fee schedule and continues to work to rectify the inequities
      of the RBRVS system as they pertain to pediatrics.

PMID- 9755277
TI  - Detection of Mycobacterium tuberculosis in gastric aspirates collected from
      children: hospitalization is not necessary.
AB  - OBJECTIVE: To compare the yields of gastric aspirates collected for culture of
      Mycobacterium tuberculosis from children evaluated as outpatients versus
      inpatients and to determine factors associated with a positive culture. METHODS:
      Retrospective study of 100 children <12 years of age with tuberculosis diagnosed
      at a pediatric referral hospital or in one of two tuberculosis control programs
      in California. RESULTS: Of the 100 children who had tuberculosis, 80 had at least
      one gastric aspirate collected. M tuberculosis was isolated from 33 (41%) of the
      80 children who had a gastric aspirate; 4 children had a positive culture from an
      aspirate subsequent to the first. Inpatients had a higher proportion of positive
      gastric aspirates than that of children who had aspirates collected as
      outpatients (48% vs 37%); however, this difference was not statistically
      significant. Resistance to isoniazid was found in three isolates (9%) of children
      all of whose presumptive source case had a susceptible strain of M tuberculosis.
      Characteristics that were associated with an approximately 50% yield from gastric
      aspirates were identification of a source case, age <2 years, birth in the United
      States, symptomatic tuberculosis, and pulmonary disease. CONCLUSIONS: The culture
      of M tuberculosis from gastric aspirates of children in the outpatient setting
      has a yield comparable to aspirates collected from hospitalized children.
      Collection of gastric aspirates in the outpatient setting will reduce both the
      cost and the inconvenience of the procedure. Although the yield from gastric
      aspirates is relatively low, important information including drug susceptibility
      patterns may be obtained. tuberculosis, gastric aspirate, children.

PMID- 9755278
TI  - Serial serum C-reactive protein levels in the diagnosis of neonatal infection.
AB  - OBJECTIVE: To evaluate serial serum C-reactive protein (CRP) levels for diagnosis
      of neonatal infection. SETTING: A regional intensive care nursery and two
      community intensive care nurseries. METHODS: All neonates treated for suspected
      bacterial infection were prospectively evaluated using a standardized clinical
      pathway. Infants were categorized as having proven sepsis (bacteria isolated from
      blood, cerebrospinal fluid, or urine culture), probable sepsis (clinical and
      laboratory findings consistent with bacterial infection without a positive
      culture), or no sepsis (findings not consistent with sepsis), without
      consideration of CRP levels. Infants whose blood cultures yielded skin flora but
      who demonstrated no other signs of bacterial infection were not considered to
      have sepsis. CRP levels were determined at the initial evaluation and on each of
      the next two mornings. Sensitivity, specificity, predictive values, and
      likelihood ratios were calculated for the first (CRP #1), second (CRP #2), higher
      of the second and third (CRP #2 and #3), or highest of all three CRP levels (CRP
      x 3). RESULTS: Sepsis was suspected within the first 3 days after birth in 1002
      infants (early-onset) and on 184 occasions in 134 older infants (late-onset).
      There were 20 early-onset and 53 late-onset episodes of proven sepsis, and 74
      early-onset and 12 late-onset episodes of probable sepsis. CRP #1 had
      sensitivities of 39.4% and 64.6% for proven or probable sepsis and 35.0% and
      61.5% for proven sepsis in early-onset and late-onset episodes, respectively. CRP
      levels on the morning after the initial evaluation (CRP #2) had higher
      sensitivities (92. 9% and 85.0% for proven or probable sepsis and 78.9% and 84.4%
      for proven sepsis in early-onset and late-onset episodes, respectively), and
      normal results were associated with lower likelihoods of infection (likelihood
      ratios for normal results of 0.10 and 0.19 for proven or probable sepsis and 0.27
      and 0.21 for proven sepsis, in early-onset and late-onset episodes,
      respectively). Three serial serum CRP levels had sensitivities of 97.8% and 98.1%
      for proven or probable sepsis and 88.9% and 97.5% for proven sepsis in early
      onset and late-onset episodes, respectively. The negative predictive values for
      CRP x 3 were 99.7% and 98.7% for both proven or probable sepsis and for proven
      sepsis in early-onset and late-onset episodes, respectively. A CRP level obtained
      at the time of the initial evaluation can be omitted without significant loss of
      sensitivity or negative predictive value: the sensitivities of CRP #2 and #3 were
      97.6% and 94.4% for proven or probable sepsis and 88.9% and 96.4% for proven
      sepsis in early-onset and late-onset episodes, respectively; negative predictive
      values were 99.7% both for proven and for proven or probable early-onset sepsis,
      97.6% for proven or probable late-onset infection, and 98.8% for proven late
      onset infection. Serial normal CRP levels were associated with a markedly reduced
      likelihood of infection as compared with that in the entire population before
      testing, with likelihood ratios ranging from 0.03 to 0.16 for the various
      subgroups. Maximum CRP levels >3 mg/dL had positive predictive values >20% for
      proven or probable early-onset infections and for proven or probable and proven
      late-onset infections, but only those >6 mg/dL had such a high positive
      predictive value for proven early-onset sepsis. CONCLUSIONS: Serial CRP levels
      are useful in the diagnostic evaluation of neonates with suspected infection. Two
      CRP levels <1 mg/dL obtained 24 hours apart, 8 to 48 hours after presentation,
      indicate that bacterial infection is unlikely. The sensitivity of a normal CRP at
      the initial evaluation is not sufficient to justify withholding antibiotic
      therapy. The positive predictive value of elevated CRP levels is low, especially
      for culture-proven early-onset infections.

PMID- 9755279
TI  - Limited evaluation of microscopic hematuria in pediatrics.
AB  - OBJECTIVE: The purpose was to determine the value of the standard laboratory and
      radiologic evaluation of microscopic hematuria in children, and to determine the
      prevalence of idiopathic hypercalciuria in those children referred for evaluation
      of unexplained microscopic hematuria. METHODS: This was a retrospective study of
      325 children referred from 1985 to 1994 for the evaluation of asymptomatic
      microscopic hematuria. The diagnostic studies reviewed included serum creatinine,
      blood urea nitrogen, serum electrolyte studies, serum complement concentration,
      antinuclear antibody, urinalysis, urine calcium to creatinine ratios, urinary
      protein to creatinine ratio and/or 24-hour urinary protein excretion, renal
      ultrasounds, intravenous pyelograms, voiding cystourethrograms, and historical
      information. RESULTS: All creatinine and electrolyte values were normal for age,
      and none of the biochemical tests obtained in the children with hypercalciuria
      was abnormal. Of the 325 patients with idiopathic microscopic hematuria, only 18
      had abnormal renal ultrasound examinations and 9 voiding cystourethrograms showed
      low-grade reflux. Hypercalciuria was found in 29 patients. The family history was
      positive for urolithiasis in 16% of patients without hypercalciuria compared with
      14% of patients with hypercalciuria. A positive family history of hematuria was
      reported in 25% of patients; 62 patients did not have hypercalciuria and 4 of the
      patients had hypercalciuria. Microscopic hematuria in children is a benign
      finding in the vast majority of children. CONCLUSIONS: Our data demonstrate that
      a renal ultrasound, voiding cystourethrogram, cystoscopy, and renal biopsy are
      not indicated in the work-up of microscopic hematuria, and microhematuria in the
      otherwise healthy child is a minimal health threat, rarely indicative of serious
      illness.

PMID- 9755280
TI  - Cost-effective treatment of phimosis.
AB  - OBJECTIVE: To determine the most cost-effective treatment for phimosis. DESIGN:
      The costs of three treatment strategies for treating phimosis were evaluated
      using a decision-tree analysis. Three therapeutic approaches were considered:
      circumcision, preputial plasty (the use of plastic surgical techniques to enlarge
      the preputial opening without removing tissue), and topical therapy with steroids
      and nonsteroidal antiinflammatories. Published failure and complication rates
      were used to calculate the cost per case. Outcome Measures. Cost in dollars to
      treat each case of phimosis. RESULTS: Topical steroid therapy was the most cost
      effective strategy, costing between $758 and $800 per case. Preputial plasty cost
      between $2515 and $2580 per case. Circumcision cost between $3009 and $3241 per
      case. CONCLUSIONS: The most cost-effective management for treating phimosis is to
      initiate topical therapy. Daily external application from the tip of the foreskin
      to the glandis corona with betamethasone 0.05% cream for 4 to 6 weeks has been
      demonstrated to be very effective, resulting in a 75% savings compared with
      circumcision. Surgical intervention should not be considered until topical
      therapy has been given an adequate trial. When contemplating surgery, the lower
      morbidity, lower costs, and tissue preservation of preputial plasty may make it
      preferable.

PMID- 9755281
TI  - Health care utilization by children with chronic illnesses: a comparison of
      medicaid and employer-insured managed care.
AB  - OBJECTIVES: This study compared utilization of health care services by children
      with chronic conditions who were insured by either Medicaid or an employer group
      in 1992 and 1993. Five chronic conditions were selected to illustrate patterns of
      service use: asthma, attention deficit disorder, diabetes, epilepsy, and sickle
      cell anemia. METHODOLOGY: Administrative databases were used to develop estimates
      of health services utilization for children <18 years of age with the five
      selected conditions, who had been enrolled for at least 6 continuous months. All
      claims for a child identified with one of these five conditions were included in
      the analysis, including claims for diagnoses and procedures not directly related
      to the primary diagnosis. Estimates were derived for eight services (eg, hospital
      admissions, emergency department (ED), home health). Data were used from two
      Independent Practice Association model health plans in two states. Differences
      across the states were controlled by selecting one Medicaid and one employer
      insured program from each of the two plans in both states. Regional variation was
      controlled for because both health plans were located in one geographical region.
      In each case, physicians were paid on a fee-for-service basis, with generally
      open access to specialists rather than primary care gatekeeper models of
      delivery: t tests were used to compare service use rates between Medicaid and
      employer-insured populations. RESULTS: A total of 8668 children across all health
      plan groups had at least one of the selected conditions. Because Medicaid
      enrolled-children tended to be younger, analyses were adjusted for age. In both
      systems, a greater percentage of Medicaid children had these five study
      conditions (5%) compared with employer-insured children (3%), suggesting that the
      Medicaid population was sicker. Mean length of enrollment during the 2-year study
      was longer for children in employer-insured programs. Children with chronic
      conditions enrolled in Medicaid managed care generally used services at a higher
      rate compared with children with similar conditions enrolled in employer-insured
      managed care. The extent of the increased use varied by condition, by service
      type, and by plan. Children with any of the chronic conditions studied had from 2
      to almost 5 times more ED visits if they were enrolled in Medicaid than if they
      were enrolled in employer-based managed care, depending on the specific
      condition. In one of the two plans, Medicaid-enrolled children had more
      outpatient services, laboratory services, and radiography services than their
      counterparts in employer-based managed care. The same pattern of use was found
      for home health services (except for children with diabetes) and for office
      visits (except for children with sickle cell). The results show higher use of all
      services by children with asthma and diabetes in Medicaid managed care compared
      with employer-based managed care. In contrast, the pattern is mixed for children
      with epilepsy and sickle cell. The sample size of children with these conditions
      was smaller than with the three other conditions, which may account, in part, for
      a varied pattern of results. The pattern of use for attention deficit
      hyperactivity disorder (ADHD) was generally different from the other conditions.
      Children with ADHD in employer-based managed care had more hospital admissions,
      hospital days, and office visits than their counterparts in Medicaid managed
      care. In contrast, Medicaid-enrolled children with ADHD had more ED visits,
      laboratory services, outpatient hospital visits, and radiography services. Other
      than ED visits, the differences in service use between Medicaid and employer
      insured children with ADHD were minimal. Of note, the pattern for ADHD is the
      same for most services for Plans A and B (excluding home health visits). This
      utilization pattern may reflect service use for comorbid conditions. Part of this
      difference may be explained by differences in Medicaid e

PMID- 9755282
TI  - Risk factors for early childhood malnutrition in Uganda.
AB  - OBJECTIVE: To assess the dietary and environmental factors influencing stunting
      and other signs of poor nutritional status of children <30 months of age in a
      central Ugandan community, whose main dietary staples are banana (matoki) and
      maize. METHODS: The study was a cross-sectional survey using stratified
      multistage random sampling to select households with a child <30 months of age in
      rural and semi-urban environments. A questionnaire was administered to mothers of
      261 infants and toddlers in their home setting. Their health status was assessed
      by clinical examination and anthropometric measurements (mid-upper arm
      circumference [MUAC], weight, and supine length). RESULTS: A large minority
      (21.5%) of the children surveyed were found in poor health after clinical
      examination: 3.8% being classified as suffering from kwashiorkor and 5.7% with
      marasmus. A high proportion of children were stunted (23. 8%), underweight
      (24.1%), or had low MUAC (21.6%). Although rural living, poor health, the use of
      unprotected water supplies, lack of charcoal as fuel, lack of milk consumption,
      and lack of personal hygiene were shown as risk factors for marasmus and
      underweight, different factors were found to be associated with risk of stunting
      and low MUAC, despite these three parameters being significantly correlated. For
      stunting the risk factors were: age of the child, poor health, prolonged
      breastfeeding (from >18 months to <24 months), low socioeconomic status of the
      family, poor education of the mother of infants <12 months, lack of paraffin as
      fuel, consumption of food of low energy density (<350 kcal/100 g dry matter),
      presence of eye pathology, and consumption of small meals. Risk factors for low
      MUAC were poor health, lack of meat and cow's milk consumption, low intake of
      energy from fat, and less well educated and older mothers. Food taboos had no
      influence on any of the anthropometric measurements. Although 93.1% of the
      children had been immunized against tuberculosis, polio, diphtheria, and measles
      and showed better general health than children who were not immunized, there was
      a high prevalence of infection in the week preceding the survey interview,
      including diarrhea (23.0%), malaria (32.3%), or cough/influenza (72.8%).
      CONCLUSIONS: This first account of dietary and environmental risk factors
      involved in the etiology of early childhood malnutrition in Uganda indicates
      differences in risk factors for marasmus and underweight compared with stunting
      and low MUAC. The high prevalence of malnutrition and current infection of
      children in this survey suggests poor immune function as a result of inadequate
      nutrition.

PMID- 9755283
TI  - Sexual abuse of children: intersection with the HIV epidemic.
AB  - OBJECTIVE: Sexual transmission of human immunodeficiency virus (HIV) is the
      predominant risk exposure among adolescents and adults reported with HIV
      infection and acquired immunodeficiency syndrome (AIDS). Although perinatal
      transmission accounts for the majority of HIV infection in children, there have
      been reports of HIV transmission through sexual abuse of children. We
      characterized children <13 years of age who may have acquired HIV infection
      through sexual abuse. METHODS: All reports by state and local health departments
      to the national HIV/AIDS surveillance system of children with HIV infection not
      AIDS (n = 1507) and AIDS (n = 7629) through December 1996 were reviewed for
      history of sexual abuse. Information was ascertained from data recorded on the
      case report form as well as investigations of children with no risk for HIV
      infection reported or identified on initial investigation. For children with a
      possible history of sexual abuse, additional data were collected, including how
      sexual abuse was diagnosed; characteristics of the perpetrator(s) (ie, HIV status
      and HIV risks); and other possible risk factors for the child's HIV infection.
      RESULTS: Of 9136 children reported with HIV or AIDS, 26 were sexually abused with
      confirmed (n = 17) or suspected (n = 9) exposure to HIV infection; mean age of
      these children at diagnosis of HIV infection was 8.8 years (range, 3 to 12
      years). There were 14 females and 3 males who had confirmed sexual exposure to an
      adult male perpetrator at risk for or infected with HIV; of these, 14 had no
      other risk for HIV infection, and 3 had multiple risks for HIV infection (ie,
      through sexual abuse, perinatal exposure, and physical abuse through drug
      injection). The other 9 children (8 females, 1 male) had no other risk factors
      for HIV infection and were suspected to have been infected through sexual abuse,
      but the identity, HIV risk, or HIV status of all the perpetrator(s) was not
      known. All cases of sexual abuse had been reported to local children's protective
      agencies. Sexual abuse was established on the basis of physician diagnosis or
      physical examination (n = 20), child disclosure (n = 15), previous or concurrent
      noncongenital sexually transmitted disease (n = 9), and for confirmed cases,
      criminal prosecution of the HIV-infected or at-risk perpetrator (n = 8). For the
      17 children with confirmed sexual exposure to HIV infection, 19 male perpetrators
      were identified who were either known to be HIV infected (n = 18) or had risk
      factors for HIV infection (n = 17), most of whom were a parent or relative.
      CONCLUSIONS: These 26 cases highlight the tragic intersection of child sexual
      abuse and the HIV epidemic. Although the number of reported cases of sexual
      transmission of HIV infection among children is small, it is a minimum estimate
      based on population-based surveillance and is an important and likely
      underrecognized public health problem. Health care providers should consider
      sexual abuse as a possible means of HIV transmission, particularly among children
      whose mothers are HIV-antibody negative and also among older HIV-infected
      children. The intersection of child abuse with the HIV epidemic highlights the
      critical need for clinicians and public health professionals to be aware of the
      risk for HIV transmission among children who have been sexually abused, and of
      guidelines for HIV testing among sexually abused children, and to evaluate and
      report such cases.

PMID- 9755284
TI  - Parent reports on willingness to accept childhood immunizations during urgent
      care visits.
AB  - OBJECTIVES: To 1) describe whether parents would be willing to accept childhood
      immunizations at urgent care visits; and 2) identify predictors of parents'
      willingness to accept childhood immunizations at urgent care visits. DESIGN AND
      PARTICIPANTS: Cross-sectional telephone survey of parents of children aged 18 to
      24 months who were underimmunized according to a computerized immunization
      tracking system and who had recently made an urgent care visit in a regional
      group-model health maintenance organization in Northern California. Chart review
      was conducted to confirm immunization status and to identify contraindications to
      vaccination. RESULTS: Of the 424 eligible participants, 351 (83%) completed
      interviews. Children with contraindications to vaccination and children who were
      actually up-to-date at the time of the urgent care visit were excluded, leaving
      263 families in the final analysis. Among these parents, 75% said they would have
      been willing to have their child immunized at the urgent care visit in question
      if the physician had suggested it. An additional 11% said they would have
      accepted vaccination if the physician told them that the shot would be safe and
      strongly encouraged them to accept it. Overall, 86% reported they theoretically
      would have accepted an immunization during the urgent care visit. In the
      multivariate analysis, the strongest predictors of stated willingness to accept
      shots at the urgent care visit were the parent: 1) not being aware that their
      child was underimmunized (odds ratio [OR] 3.5, 95% confidence interval [CI], 1.6
      7.7); 2) perceiving that the child was not very sick at the visit (OR 1.8, 95%
      CI, 1.1-3.0); 3) being less concerned about the risk of shots (OR 1.8, 95% CI,
      1.2-2.5); and 4) being of nonwhite race (OR 3.6, 95% CI, 1.6-7.7). Income and
      education were not significantly associated with reported willingness to accept
      immunization. CONCLUSIONS: We conclude that most parents of underimmunized
      toddlers report being willing to accept immunizations during urgent care visits
      if the clinician recommends it. More effective ways of alerting providers in
      urgent care settings when immunizations are due, such as indications on a chart
      or registration form, hold promise for improving immunization coverage rates.

PMID- 9755285
TI  - Computer-assisted diagnosis of pediatric rheumatic diseases.
AB  - OBJECTIVE: AI/RHEUM is a multimedia expert system developed originally to assist
      in the diagnosis of rheumatic diseases in adults. In the present study we
      evaluated the usefulness of a modified version of this diagnostic decision
      support system in diagnosing childhood rheumatic diseases. METHODOLOGY: AI/RHEUM
      was modified by the addition of 5 new diseases to the knowledge base of the
      system. Criteria tables for each of the diseases included in the knowledge base
      were modified to suit the needs of children. The modified system was tested on 94
      consecutive children seen in a pediatric rheumatology clinic. RESULTS: AI/RHEUM
      made the correct diagnosis in 92% of the cases when the diagnosis was available
      in the knowledge base of the system. It was also shown to be effective in the
      education of pediatric trainees through its multimedia features. CONCLUSIONS:
      AI/RHEUM is an expert system that may be helpful to the nonspecialist as a
      diagnostic decision support system and as an educational tool.

PMID- 9755286
TI  - Endogenous glutathione conjugates: occurrence and biological functions.

PMID- 9755287
TI  - The B1 receptors for kinins.

PMID- 9755288
TI  - Prediction of pharmacokinetic alterations caused by drug-drug interactions:
      metabolic interaction in the liver.

PMID- 9755289
TI  - Receptors for purines and pyrimidines.

PMID- 9755290
TI  - Classification and biology of astrocytic gliomas.
AB  - The presented classification of astrocytic gliomas follows the system adopted by
      the WHO which was last published in 1993. The nosographic position of each tumour
      type is discussed in relation to previous positions and the rationale of changes
      is provided. The biology and pathology of anaplasia, leading from astrocytoma to
      glioblastoma, are discussed briefly. The increasing genotypic and phenotypic
      heterogeneity is described in its progressive stages. A series of genetic changes
      are associated with the main histologic features of malignancy , such as TP53
      mutations, EGFR amplification, CDKN2 deletion, etc. The genetic differences
      between primary and secondary glioblastomas are emphasised. Tumour-associated
      biological events are presented: cell invasion and spread, necrosis and apoptosis
      and angiogenesis are all discussed in some detail. Of each event a short survey
      on the principal phenotypic and molecular features is given with emphasis on
      their significance to pathogenesis. Each tumour type is briefly summarised from
      epidemiological, clinical and pathological standpoints.

PMID- 9755291
TI  - New frontiers in therapy of malignant gliomas.
AB  - The prognosis of patients with malignant gliomas remains dismal despite the
      development of a multidisciplinary approach to their treatment. There is a strong
      need for novel therapeutic approaches that can make a definite impact in the
      clinical course of these tumours. Although there have been several advances in
      diagnostic modalities, surgical techniques and cytotoxic therapies, the
      development of newer therapies has been hampered by the limited understanding of
      the factors that determine the biological nature of gliomas. However, inroads are
      now being made into the understanding of the genetic make-up, biological
      behaviour and therapeutic response of these tumours, which are expected to pave
      the way for new modes of treatment. In this article, we review the advances made
      in the identification of potential targets for glioma therapy and the recent
      clinical trials utilising biological therapies and newer cytotoxic agents.

PMID- 9755292
TI  - Trends in surgical management of astrocytomas and other brain gliomas.
AB  - In recent years, surgical treatment of cerebral gliomas has made significant
      technical advances (e.g. microsurgery and neuronavigation) and has also
      benefitted from improvement in diagnostic techniques and biopathology. Thanks to
      this progress, there has been a reduction in the surgical mortality and morbidity
      of highly malignant neoplasms such as glioblastoma multiforme and
      medulloblastoma, although there has not been any significant improvement in
      survival. On the other hand, for a specific group of circumscribed and resectable
      brain gliomas, modern neurosurgery is potentially curative in a high proportion
      of cases, even if the gliomas are located in deep and previously inaccessible
      brain regions. These "benign" variants of cerebral gliomas occur mainly in
      children and young adults, i.e., in subjects with a long life-expectancy.
      Astrocytoma, oligodendroglioma and ependymoma are a third group of cerebral
      gliomas for which modern neurosurgery offers interesting new possibilities.

PMID- 9755293
TI  - Modern aspects of radiation therapy for glial tumours of the brain.
AB  - Radiation was conclusively proved to be of value in the treatment of malignant
      gliomas in the late 1970's where it enabled an approximate doubling of the
      survival time. Further study defined a number of prognostic factors which provide
      a basis for selecting patients for treatment. The introduction of computer
      tomography (and later magnetic resonance) scanning allowed a more rational
      approach to target volume definition and a reduction in radiation-related
      morbidity. Dose-ranging studies defined a standard approach to treatment (60 Gray
      in 30 fractions). Since then numerous attempts have been made to improve on these
      results. Marginal benefits have been claimed for altered fractionation schemes,
      limited volume dose escalation (implants and stereotaxy), radiation sensitisers
      and particle therapies. However none has become routine in clinical practice.
      Advances in planning technology have allowed a further reduction in the volume of
      normal brain irradiated and the potential for dose escalation. Low grade
      astrocytoma has not been examined in the same way and great doubt exists with
      respect to optimal treatment. There is a great opportunity for research to
      realise the potential in the new techniques for improving the outlook for
      patients with malignant glioma and in clarifying the role of radiation in low
      grade tumours.

PMID- 9755294
TI  - Heparin and nitric oxide treatment in experimental acute pancreatitis in rats.
AB  - The aim of this study was to investigate the impact of L-arginine (nitric oxide
      synthase substrate), L-NG-nitro-L-arginine (nitric oxide synthase inhibitor), and
      heparin on the pancreas microcirculation, serum IL-6 level and microscopic
      alterations of the pancreas in acute pancreatitis in rats. Acute pancreatitis was
      induced by 4 i.p. injections of cerulein (15mg/kg). Microcirculatory values were
      measured by means of laser Doppler flowmetry 5 h after the first cerulein
      injection. Remarkable histopathological changes in the pancreas, including
      parenchymal necrosis, an elevation of serum IL-6 level, and a significant drop of
      pancreatic capillary perfusion was observed in rats with nitric oxide synthase
      inhibition. L-arginine improved the pancreatic microcirculation but worsened the
      microscopic alterations within the pancreas. Heparin had a beneficial effect on
      the microcirculatory values, serum IL-6 concentration, and morphologic changes.
      Authors conclude that inhibition of nitric oxide synthase aggravates acute
      pancreatitis. L-arginine treatment improves pancreatic perfusion but potentiates
      morphological alterations. Heparin, improving the microcirculation and
      inflammatory changes within the pancreatic gland, may be considered as a
      promising therapeutic agent in acute pancreatitis.

PMID- 9755295
TI  - Single-dose pharmacokinetic study of ciprofloxacin and fleroxacin in healthy
      adult Nigerian volunteers.
AB  - The kinetics of absorption, distribution and elimination of ciprofloxacin and
      fleroxacin (following an intravenous dose of 200 mg), were evaluated in 24 adult
      healthy male Nigerian volunteers. Appropriate mathematical models were applied
      with the aid of a microcomputer software program for the estimation of the basic
      pharmacokinetic parameters. Appropriate statistical tests and profiles formed the
      basis for accepting or rejecting a proposed model. For parametric comparisons
      between the profile of the two drugs, the null hypothesis of no difference in
      their pharmacokinetic profile was proposed. All statistical tests were performed
      at a significance level of 95% (alpha = 0.05) and the 95% confidence level was
      determined where appropriate. Additionally, the model-independent or stochastic
      method of analysis was also employed in the pharmacokinetic evaluation of the
      blood level data. The parametric estimates obtained from both methods were
      compared. The plasma elimination half-life (t1/2) was estimated as 13.8 +/- 5.5 h
      for fleroxacin and 7.5 +/- 4.0 h for ciprofloxacin; the maximal plasma
      concentration (Cmax) was 0.8 +/- 0.3 and 2.3 +/- 1.0 mg/l for fleroxacin and
      ciprofloxacin, respectively, whilst the volume of distribution (Vd) was 2.5 +/-
      1.6 and 0.4 +/- 0.3 liters/kg for fleroxacin and ciprofloxacin, respectively. 71
      and 70% of unchanged drug were excreted in urine for fleroxacin and
      ciprofloxacin, respectively. With respect to comparative values, the results
      confirmed trends already observed in the literature, particularly as regards the
      t1/2. However, for fleroxacin there was a significant deviation from the
      literature trends with respect to Vd, Cmax and AUC. The results also confirmed
      earlier findings, advocating a once-daily dosage schedule for fleroxacin also in
      the Negroid population.

PMID- 9755297
TI  - Erythromycin resistance in group A beta hemolytic streptococcus.
AB  - The incidence of erythromycin resistance and the phenotypic pattern of resistance
      have been studied in 130 group A beta-hemolytic streptococcus (GABHS) strains,
      isolated from throat swab obtained in children affected by acute
      pharyngotonsillitis. A total of 56 (43%) GABHS strains of 130 were resistant to
      erythromycin. Among these 56 strains, we found that 7 (12.5%), 18 (32.1%) and 31
      (55.3%) showed the cMLS, iMLS and M phenotype, respectively. The iMLS and M
      phenotypes appear to be the most widely represented ones. Their low level of
      resistance to macrolides could allow the use of the more recent macrolides
      characterized by higher tissue concentration which could overcome such a
      resistance.

PMID- 9755296
TI  - Comparative activity of piperacillin/tazobactam against clinical isolates of
      extended-spectrum beta-lactamase-producing Enterobacteriaceae.
AB  - beta-Lactam resistance on the part of the Enterobacteriaceae causes serious
      therapeutic problems in our institutions due to their production of extended
      spectrum beta-lactamases (ESbetaLs). We studied the in vitro activity of beta
      lactam/beta-lactamase inhibitor combinations and third-generation cephalosporins
      and monobactams against 71 clinically relevant Enterobacteriaceae which produced
      TEM- and SHV-derivative ESbetaLs. Of the single drugs and combinations tested,
      piperacillin/tazobactam proved to be the most effective. Piperacillin/tazobactam
      was highly active against Proteus mirabilis, with minimum inhibitory
      concentrations (MICs) ranging from 0.125 to 16 microg/ml; Escherichia coli (MICs
      from 2 to 16 microg/ml) and Serratia marcescens (MICs from 4 to 8 microg/ml),
      while its activity against Klebsiella pneumoniae ESbetaL producers turned out to
      be closely related to the type and the amount of enzyme produced, the MIC ranging
      from 1 to 128 microg/ml. The antibacterial activity of piperacillin/tazobactam
      was stronger than that of ticarcillin/clavulanate, ceftriaxone, cefotaxime,
      ceftazidime and aztreonam, and the combination shared favorable in vitro activity
      properties against the ESbetaL producers with imipenem which, however, should be
      kept as reserve product.

PMID- 9755298
TI  - Mecillinam activity compared to ampicillin, trimethoprim/sulfamethoxazole,
      ciprofloxacin and nitrofurantoin against urinary tract isolates of gram-negative
      bacilli.
AB  - Recent Canadian, American and European studies have reported increased ampicillin
      and trimethoprim/sulfamethoxazole resistance among urinary tract isolates of
      Escherichia coli. This trend suggests that a reevaluation of first- and second
      line therapies for the treatment of community-acquired urinary tract infections
      is necessary. Mecillinam, a beta-lactam with preferential activity against gram
      negative penicillin binding protein 2 (unlike other beta-lactams which
      preferentially bind gram-negative penicillin binding proteins 1a, 1b or 3), may
      offer clinically significant activity against ampicillin-resistant and
      trimethoprim/sulfamethoxazole-resistant E. coli. To test this assertion, the
      activity of mecillinam was compared with ampicillin,
      trimethoprim/sulfamethoxazole, nitrofurantoin and ciprofloxacin against 258
      consecutive gram-negative urinary tract isolates collected at a Canadian tertiary
      care hospital. Mecillinam demonstrated significantly better activity than
      ampicillin and trimethoprim/sulfamethoxazole and significantly less activity than
      ciprofloxacin and nitrofurantoin against the 258 isolates tested. Against E. coli
      isolates specifically, mecillinam was significantly more active than ampicillin
      and trimethoprim/sulfamethoxazole (p < 0. 001) and as active as ciprofloxacin and
      nitrofurantoin. Mecillinam was active against 91.9% of ampicillin-resistant E.
      coli and 95.9% of trimethoprim/sulfamethoxazole-resistant E. coli. We conclude
      that mecillinam should be reevaluated for potential use in the treatment of
      community-acquired urinary tract infections.

PMID- 9755299
TI  - Effects of a new topic amikacin formulation on chemotaxis and release of
      profibrotic factors by human monocytes.
AB  - Aminoglycosides, widely used because of their large-spectrum antibiotic effects,
      should not interfere with the healing process of an ulcer or an infected wound.
      We evaluated the effects of amikacin or the excipients present in the topic
      formulation BG 90, powder 2. 5% (Boniscontro e Gazzone S.r.l., Rome, Italy), on
      human monocyte chemotaxis and the release of profibrotic factors by resting or
      lipopolysaccharide (LPS)-activated monocytes. The chemotactic response of
      monocytes to zymosan-activated serum is not modified in vitro by pre-incubation
      of the cells with amikacin (2 and 10 microg/ml/10(6) cells) or excipients.
      Unstimulated monocytes did not secrete appreciable amounts of cytokines. Vice
      versa, amikacin-stimulated cells released platelet-derived growth factor AB (PDGF
      AB) (about 340 pg/ml), transforming growth factor (TGF)-beta1 (about 10 pg/ml),
      and tumour necrosis factor (TNF)-alpha (over 1,100 pg/ml); among excipients, ZnO
      and vitamin E induced PDGF-AB release (about 320 and, respectively, 200 pg/ml),
      while stimulation of monocyte monolayers by the other excipients did not lead to
      appreciable cytokine release. As expected, LPS-activated human monocytes produced
      PDGF-AB, TGF-beta1, and TNF-alpha. When monocytes were co-stimulated with LPS and
      amikacin, the PDGF-AB and TGF-beta1 values almost overlapped with those from the
      stimulation of cells with LPS alone, while TNF-alpha production was slowly
      reduced. The results show a stimulating effect of aminoglycoside on the
      production of profibrotic factors and, therefore, on the healing process of
      wounds in addition to a modulating effect on the production of pro-inflammatory
      cytokines like TNF-alpha. Moreover, ZnO and tocopherol (free-radical scavengers),
      used as excipients in the topic formulation, induce the release of growth factors
      with profibrotic activity (PDGF-AB). Further research is warranted to explore the
      effects of this formulation in vivo, verifying whether the association of the
      antibiotic with scavengers has a double advantage in topical amikacin: on the one
      hand, it could limit the damage from free radicals, and on the other it could
      favour tissue healing.

PMID- 9755300
TI  - Effects of cefepime, cefixime and ceftibuten on murine gut colonization by
      Candida albicans.
AB  - Crl:CD1(ICR) BR mice were fed chow containing Candida albicans or regular chow.
      Both groups were subsequently given either antibiotics or normal saline. Stool
      cultures were performed before, at the end of treatment and 1 week after
      treatment, to determine the effect on the stool yeast concentration. Candida
      colonized mice treated with cefepime, cefixime or ceftibuten had higher (however
      not significantly) counts of the yeast in their stools than control Candida-fed
      mice treated with saline. A group of Candida-fed mice were treated with
      ceftriaxone, which is known to increase the yeast stool concentration
      significantly and served as positive control. Mice fed regular chow and treated
      with the study drugs or saline did not have any yeasts in their stools.
      Dissemination of Candida did not occur.

PMID- 9755301
TI  - Inhibition of malaria-infected erythrocytes by deoxyspergualin: effect on in
      vitro growth of malarial cultures.
AB  - The effect of deoxyspergualin (DSG) on the K1 strain of human malarial parasite
      Plasmodium falciparum in vitro was studied to test a possible new antimalarial
      chemotherapy. Hypoxanthine labeled with tritium (3H) was used to assess
      macromolecular synthesis. The inhibitory effects of DSG on the parasite peaked
      after 72 h of incubation. Parasitemia without DSG treatment was 9%, whereas at a
      DSG concentration of more than 156 microg/ml it was less than 1%. The amount of
      [3H]hypoxanthine taken up decreased with increasing DSG concentration. DNA
      synthesis of malarial activity decreased with increasing DSG concentration. These
      findings provide more evidence for the effects of DSG on this malarial parasite.
      As in previous in vivo studies done with DSG, the in vitro findings showed that
      DSG may be a new antimalarial drug.

PMID- 9755302
TI  - Establishment and characterization of cisplatin-resistant human epidermoid
      carcinoma cell line, A431 cell.
AB  - Cisplatin, cis-diamminedichloroplatinum(II) (CDDP) is one of the most important
      anticancer agents, initially producing good responses in various tumors. However,
      resistance to this drug often develops in various tumors, and additional
      administration decreases its chemotherapeutic efficacy. The precise mechanism of
      acquisition of resistance to this drug is still uncertain. However in the present
      study, we established two CDDP-resistant sublines A431/CDDP1 and A431/CDDP2 from
      human epidermoid carcinoma cell line A431. These resistant sublines were
      constituted by exposing A431 cells to a gradually increasing dose of CDDP
      (A431/CDDP1), and by mutagenic induction with mutagen (A431/CDDP2). A431/CDDP1
      and A431/CDDP2 have developed 3.1 and 2.7 times more resistance to CDDP than the
      original A431 cell in terms of IC50. The two CDDP-resistant sublines showed cross
      resistance to the CDDP analogue, carboplatin (CBDCA), but not to other
      chemotherapeutic drugs such as Adriamycin (ADR) and 5-fluorouracil (5-FU). These
      CDDP-resistant sublines were transplanted into nude mice to demonstrate the
      resistance to CDDP treatment in vivo. According to the in vitro assay, the
      mechanism of resistance in A431/CDDP1 and A431/CDDP2 seems to be based on a
      reduction of intracellular accumulation of CDDP, because their platinum
      concentration, which is the major component of CDDP, significantly declined. The
      established CDDP-resistant sublines may be used in further trials to improve the
      understanding of the mechanisms of resistance to CDDP.

PMID- 9755303
TI  - Antineoplastic and cytogenetic effects of platinum(II) and palladium(II)
      complexes with pyridine-2-carboxyaldehyde-thiosemicarbazone.
AB  - The effect of six novel complexes of Pt(II) and Pd(II) with pyridine-2
      carboxyaldehyde thiosemicarbazone (HPyTsc) on sister chromatid exchange rate and
      human lymphocyte proliferation kinetic was studied. Also, the effect of Pt(II)
      and Pd(II) complexes against leukemia P388 was investigated. Among these
      compounds, the most effective in inducing cytogenetic and antineoplastic effects
      are the complexes [Pd(PyTsc)2] and [Pt(PyTsc)2]. Next in order of magnitude in
      inducing antineoplastic and cytogenetic effects is the compound [Pt(HPyTsc)2]Cl2
      while the rest, i.e. [Pd(PyTsc)Cl], HPyTsc, [Pd(HPyTsc)2]Cl2, and [Pt(PyTsc)Cl],
      show marginal cytogenetic and antineoplastic effects.

PMID- 9755304
TI  - New strategies in the treatment of infectious complications in haematology and
      oncology: is there a role for out-patient antibiotic treatment of febrile
      neutropenia?
AB  - Febrile neutropenia is associated with a significant risk of complications and
      mortality. Patients with neutropenia secondary to cytostatic chemotherapy who
      develop fever are normally admitted to hospital and treated promptly with broad
      spectrum antibiotics. Over the last 10 years, chemotherapy for solid tumours has
      been shifting out of the hospital setting into the ambit of community-based
      oncologists, and out-patient treatment with complex multidrug protocols is
      becoming increasingly common. In North America high-dose protocols combined with
      peripheral blood stem cell transfusion are already being administered on an out
      patient basis. With the increase in the numbers of out-patients undergoing
      multidrug chemotherapy, there has been a corresponding rise in the severity and
      duration of neutropenia and in the incidence of associated infections. Patients
      with neutropenia of short duration (<7 days) and fever are at a relatively low
      risk for complications, and in these circumstances, out-patient antibiotic
      treatment is an alternative to costly hospitalisation. Drugs, whose antimicrobial
      coverage and pharmacokinetics make them particularly suitable for out-patient
      treatment of febrile neutropenia, include intravenous and oral quinolones and,
      for once-daily dosing, intravenous glycopeptides, ceftriaxone and intravenous
      aminoglycosides. Response rates of 60-95% have been achieved with such regimens
      in clinical trials, with hospital admission avoided in 75-95% of the cases. There
      is no doubt that out-patient treatment improves the quality of life of cancer
      patients. In Europe, however, there is a need for randomised clinical trials to
      support the establishment of out-patient-based treatment of febrile neutropenia.
      Out-patient antibiotic treatment of febrile neutropenia is still not standard
      practice, and community-based providers of such treatment must be adequately
      equipped and experienced in the management of this condition.

PMID- 9755305
TI  - Growth factor receptors as targets for therapy in pediatric brain tumors.
AB  - Growth factor receptors (GFRs) have been described as overexpressed in several
      types of brain tumors. Overexpression of these transmembrane proteins is
      considered to be an important part of tumorigenesis. Genetic as well as
      epigenetic modulation of the receptors have to be considered when trying to
      understand the role of GFRs in tumors or as targets for tumor therapy. GFR
      function can be modulated by membrane components (e.g. gangliosides) or by the
      change in receptor glycosylation. These types of changes and the occurrence of
      the expression of mutated receptor expressed in tumor cell can result in altered
      signaling. In this review, we have focused on GFRs, their expression and
      mutations in brain tumors. Recently the correlation between GFR expression and
      patient outcome has suggested that these tyrosine kinases and their signaling
      might play a decisive role in the course of patients with brain tumors. The
      importance of GFRs as possible targets for brain tumor therapy is also discussed.

PMID- 9755306
TI  - Headache and Chiari I malformation in the pediatric population.
AB  - There has been disagreement regarding surgical intervention in treating pediatric
      patients with Chiari I malformation with headache as sole complaint. Therefore,
      we retrospectively reviewed our experience over a 6-year period, with patients
      less than 5 years of age (mean = 34.8 months) with radiographically confirmed
      Chiari I malformation. We identified 7 patients who presented with headaches as
      their only complaint. The headaches varied in location and severity. All patients
      were treated with posterior fossa decompression and syringosubarachnoid shunt
      when indicated. At follow-up, all patients were noted to have rapid clinical
      improvement (mean = 11.6 weeks) and remain asymptomatic. Our data suggest that
      patients less than 5 years of age with Chiari I malformation benefit from
      surgical decompression when presenting with a chief complaint of headache.

PMID- 9755307
TI  - Suprasellar germinoma associated with Cushing's disease and diabetes insipidus in
      a child.
AB  - Cushing's disease is described in a child with a suprasellar germinoma. The
      patient presented with all of the classic stigmata of Cushing's disease as well
      as diabetes insipidus, but after surgical resection of the lesion was found to
      have pathology incompatible with an ACTH-secreting tumor. We believe that this is
      the first reported incidence of Cushing's disease associated with a suprasellar
      germinoma. The implications of this unusual association are discussed.

PMID- 9755308
TI  - Potential prognostic factors of relapse-free survival in childhood optic pathway
      glioma: a multivariate analysis.
AB  - There is still no consensus on the natural history and optimal management of
      optic pathway gliomas (OPG) in children. In order to tackle optimal management
      issues, we need to clearly understand the prognostic and confounding factors
      affecting relapse of OPG. We propose the use of the Cox proportional hazards (PH)
      model in a retrospective study of childhood OPG of 69 children seen from 1977 to
      1994. We have developed a comprehensive model capable of multivariate analyses
      and handling time-dependencies. Our studies showed that relapse-free survival
      improves with increasing age, the presence of neurofibromatosis 1 (NF1), and
      chemotherapy and radiotherapy (p < 0.0005). Sex, tumor position and surgery do
      not significantly affect survival. Older children with NF1 have extremely good
      prognosis. We noted behavior that departs from the strictly proportional hazards
      model, but results were inconclusive.

PMID- 9755309
TI  - Spinal teratomas versus hamartomas.

PMID- 9755310
TI  - An unusual variant of a growing skull fracture in an adolescent.
AB  - A great majority of growing skull fractures occur in infancy and earlychildhood.
      Since the growth of brain is necessary as a driving force for these lesions to
      occur, almost all reported cases have been before the first 3 years of life.
      Although a number of uncommon locations, such as basiooccipital and skull base
      areas, have been reported, they are commonly located on calvaria. The authors
      report a growing skull fracture on the orbital roof in a 16-year-old female
      admitted to hospital with complaints of headache and seizures. She had had an
      orbital trauma 8 years before. CT scan revealed a hypodense lesion in the right
      frontal lobe and a diastatic fracture line on the right orbital roof. A right
      craniotomy was performed. Excision of arachnoid loculations and duraplasty were
      carried out. This is an unusual condition with respect to the location of the
      lesion, as well as the age of the patient.

PMID- 9755311
TI  - Treatment of intracranial ependymoma by surgery alone.
AB  - OBJECTIVE: This study aimed to determine the safety of deferring radiotherapy in
      pediatric intracranial ependymoma following a radiographically confirmed gross
      total resection in patients with localized disease. METHODS: Children over age 3
      were recruited prospectively from 1990 to 1997, following a surgical impression
      and radiologic confirmation of a gross total resection of an intracranial
      ependymoma. RESULTS: 10/32 cases of intracranial ependymomas were both eligible
      and gave consent. 7 remain free of disease without further intervention. 3
      recurred, 2 were salvaged with surgery and radiotherapy, none died. CONCLUSIONS:
      Deferral of radiotherapy following gross total resection alone is a safe option
      in supratentorial ependymomas. The pattern of recurrence is usually local and
      patients may be salvaged with additional surgery with or without radiotherapy.

PMID- 9755312
TI  - 15-year-old young woman with morning headaches.

PMID- 9755314
TI  - Spinal teratomas versus hamartomas 

PMID- 9755313
TI  - Ventriculoperitoneal shunt obstruction presenting as apnea and bradycardia.

PMID- 9755315
TI  - Intraoperative monitoring.

PMID- 9755316
TI  - Bisphenol A diglycidyl ether as a potential metabolic source of bisphenol A.

PMID- 9755317
TI  - Surgical results after soft system stabilization of the lumbar spine in
      degenerative disc disease--long-term results.
AB  - After having reported preliminary results of soft system stabilization according
      to Graf in a series of 27 patients with degenerative disc disease of the lumbar
      spine in early 1995 the authors report long term clinical and radiological
      results of this patient series (n = 25). At a mean period of postoperative
      observation of 50 months excellent, good, satisfactory, moderate and poor results
      were obtained in 62, 9%, 11, 1% and 11, 1%, 7, 4% and 7, 4% of the patients,
      respectively. The well-known phenomenon of loss of disc height at the level of
      posterolateral fusion and instrumentation as well as overcharge of adjacent
      segments were not observed after soft system stabilization. Regional as well as
      global lumbar lordosis were maintained and, although statistically not
      significant, an increase of intervertebral distance was observed in adjacent
      segments in flexion of the lumbar spine. These phenomena might represent
      pressurization of instrumented as well as adjacent discs after the insertion of
      ligament prostheses. It is the impression of the authors, that the Graf technique
      leads to good surgical results in degenerative disc disease with destabilization
      of lumbar motion segment(s) if the following criteria are strictly respected: 1.
      No or only mild arthrotic changes of the facet joints 2. Preferably minor disc
      degeneration/only mild loss of intervertebral distance. 3. Well trained low back
      muscles and 4. A clear-cut, repeatedly demonstrated pain-relief on trial
      anaesthesia of the corresponding articular nerves and while wearing a probatory
      jacket.

PMID- 9755318
TI  - Radiological investigations and intra-operative evoked potentials for the
      diagnosis of nerve root avulsion: evaluation of both modalities by intradural
      root inspection.
AB  - Fourteen patients with traumatic brachial plexus injuries underwent intradural
      inspection of cervical nerve roots to evaluate radiological and intra-operative
      electrophysiological findings concerning cervical nerve root avulsion from the
      spinal cord. Four neurosurgeons of our department assessed independently from
      each other both myelography and CT-myelography concerning intradural nerve root
      lesions. Each neurosurgeon assessed a total of 26 cervical nerve roots. Two
      investigators assessed 6/26 and 2 investigators 7/26 nerve roots falsely
      concerning ventral or/and dorsal root lesions compared with the findings on
      intradural inspection (23% and 27% false findings). There was a considerable
      variance concerning the assessibility and findings among the 4 neurosurgeons.
      Reconstructive surgery was performed after a mean interval of 6.5 months
      following trauma and 2 weeks following intradural inspection. After exposure of
      the brachial plexus and the cervical nerve roots in question via a ventral
      approach, 13 cervical nerve roots were stimulated electrically close to the
      neuroforamen and cortical evoked potentials (root-SEPs) were recorded from the
      contralateral postcentral region. All 5 roots with SEPs were intact (no root
      lesion) and all 8 roots without SEPs showed interrupted (ventral or/and dorsal)
      rootlets on intradural inspection. Our results demonstrate that false
      radiological findings concerning root lesions are possible. Intra-operative root
      SEPs seem to be a useful aid for evaluation of cervical nerve root lesions.
      However, more electrophysiological data are necessary to ascertain, if this
      modality is able to replace intradural inspection in unclear radiological cases
      in the future.

PMID- 9755319
TI  - Somatosensory and motor evoked potentials in patients with tumours in the spinal
      canal.
AB  - Motor and sensory evoked potentials were recorded in 27 patients with expanding
      spinal tumour. The patients were divided into 2 groups: I. tumours at the level
      of the spinal cord and II. at the level of the cauda equina. On the basis of the
      localization of the tumour, midline and lateral subgroups were distinguished. The
      latencies of motor evoked potentials were prolonged in most of the patients, even
      those without paresis, in both groups. The motor evoked potentials detected
      subclinical motor lesions in 7 patients. All patients but one manifested sensory
      deficits, which could not be shown with the somatosensory evoked potentials.
      Significantly more prolonged cortical motor latencies were found in most of the
      patients with a laterally located tumour on the tumour side than contralaterally,
      whereas in somatosensory evoked potentials this difference was not apparent. On
      the basis of these observations, we concluded that motor evoked potentials, 1.
      could more reliably detect the neural deficit than somatosensory evoked
      potentials; 2. could show the side where the tumour was located; 3. proved useful
      in the detection of subclinical motor lesions. The general conclusion may be
      drawn that this electrophysiological method can provide useful information for
      the surgeon.

PMID- 9755320
TI  - Demonstration of the optic pathway in sellar/juxtasellar tumours with visual
      disturbance on MR imaging.
AB  - OBJECTIVE: To prospectively compare the demonstration of the intracranial optic
      pathway in patients with sellar/juxtasellar tumours and with clinical evidence of
      visual disturbance using either spoiled gradient recalled acquisition in steady
      state (SPGR) or conventional spin echo (CSE) T1-weighted imaging. MATERIALS AND
      METHODS: We studied 108 patients with sellar/juxtasellar tumours presenting
      visual disturbance. Visualization of the optic pathway (nerves, chiasm, tracts)
      was compared between CSE T1-weighted coronal image and SPGR coronal image. In 18
      patients, SPGR imaging was performed before and after administration of Gd-DTPA
      and visualization of the optic pathway was compared. RESULTS: On CSE T1-weighted
      coronal images of 108 patients with visual disturbance, the rates for
      visualization of the optic nerves, chiasms and tracts were 50%, 77.8% and 89.8%
      respectively. In contrast, on SPGR coronal image the rates were 80.6%, 96.3% and
      92.6% respectively. The rates of visualization of the optic pathway were greater
      in non-enhanced that in those with enhancement. The rates of visualization in
      patients with recurrent tumours were less than those in patients with primary
      tumours. The rate of visualization of optic nerves in patients with meningioma
      was less than in patients with pituitary adenoma, craniopharyngioma or Rathke
      cleft cyst. CONCLUSION: The rate of visualization of optic pathway structures on
      SPGR imaging (without enhancement) is greater than that on CSE T1-weighted
      imaging. It is important to understand the accurate position of the optic
      pathways with using new MR modality especially in surgical planning for lesions
      around the sella turcica.

PMID- 9755321
TI  - Gamma-knife radiosurgery for brain metastases of renal cell carcinoma: results in
      23 patients.
AB  - From Jan. 1993 to Sept. 1995 23 patients suffering from brain metastases from
      renal cell carcinoma were treated with the Leksell Gamma Knife at the University
      of Vienna. At the time of diagnosis 13 patients had single and 10 patients
      presented with multiple metastatic lesions with a total of 44 metastases in MRI
      scans. Median tumour volume was 5500 cmm (range 100-24000 cmm). Predominant
      neurological symptoms and signs were different forms of hemiparesis, focal and
      generalized seizures, cognitive deficit, headache, dizziness, ataxia and CN XII
      paresis. Fourteen patients received Gamma Knife Radiosurgery (GKRS) with a median
      dose of 22 Gy (range 8-30 Gy) at the tumour margin. Nine patients underwent a
      combined treatment of a radiosurgical boost with a median dose of 18 Gy (range 10
      22 Gy) at the tumour margin followed by Whole Brain Radiotherapy (total dose 30
      Gy/2 weeks). In 20 patients tumour volume reduction up to 30% of the primary
      tumour volume was found after 4 weeks, evaluated on CT or MRI. A total remission
      was seen in 4 cases 3 months after GKRS. We achieved a local tumour control of
      96%. Rapid neurological improvement after GKRS was seen in 17 patients. The
      median survival time was 11 months; the one-year actual survival in this
      unselected group was 48%. Five long term survivors were still alive, 18 patients
      had subsequently died, 15 of them of general tumour progression. GKRS induces a
      significant tumour remission accompanied by rapid neurological improvement and
      therefore provides the opportunity for extended high quality survival. Neither
      local tumour control was improved nor CNS relapse free survival was prolonged
      significantly by additional WBRT.

PMID- 9755322
TI  - Choroid plexus carcinoma in infants: report of two cases and review of the
      literature.
AB  - Choroid plexus carcinoma (CPC) is a rare malignant brain tumour which occurs
      predominantly in childhood. We present the cases of two infants with CPC. One, a
      6-month-old boy with the tumour in the right lateral ventricle, who died of a
      postoperative intracranial haemorrhage and severe gastrointestinal bleeding, and
      the other, a 9-month-old boy with the tumour in the fourth ventricle, who has
      been well without recurrence for 12 months after total removal in combination
      with chemotherapy using cisplatin and VP-16 and local radiotherapy. In the 54 CPC
      cases in children under 2 years of age including our 2 cases in which the
      clinical results were described in the literature since 1983, tumour location
      (lateral ventricle, p = 0.0225), surgery (gross total resection, p = 0.0447), and
      chemotherapy (yes, p = 0.0010) were revealed to be significant positive
      prognostic factors by the univariate analysis using the log rank test, and
      surgery (gross total removal, p = 0.0259) and chemotherapy (yes, p = 0.0016) were
      independent, significant positive prognostic factors in the multivariate analysis
      using the Cox proportional hazard regression model. Although there is a risk in
      doing a statistical analysis of other people's reports, these results suggest
      that, at present, the gross total removal of the tumour with intensive
      chemotherapy is the best choice of initial treatment for young children with CPC,
      and that radiotherapy should be considered for patients after 24 months of age
      and/or should be performed locally.

PMID- 9755323
TI  - Prediction of vertebral artery compression in patients with hemifacial spasm
      using oblique sagittal MR imaging.
AB  - To discriminate between the various compressing vessels of the facial nerves in
      patients with hemifacial spasm, pre-operative oblique sagittal gradient-echo MR
      imaging was performed. Forty-two patients underwent pre-operative MR imaging and
      microvascular decompression. The MR images were divided according to findings
      into three groups as follows: Group A, a thick and/or long high-intensity line
      along the root exit zone (REZ) of the facial nerve; Group B, a thin and/or short
      high-intensity line along the REZ; and Group C, an unreliable image around the
      REZ. Fifteen images were classified as Group A, 19 as Group B, and 8 as Group C.
      In Group A, vertebral artery (VA) compression was confirmed intra-operatively in
      12 cases and posterior inferior cerebellar artery (PICA) or anterior inferior
      cerebellar artery (AICA) compression in 3. In Group B, PICA or AICA compression
      was confirmed intra-operatively in all cases. In Group C, PICA or AICA
      compression was confirmed intra-operatively in 7 cases and no compression in one.
      In all cases of VA compression of the facial nerve, the oblique sagittal gradient
      echo images demonstrated a thick and/or long high intensity line along the REZ.
      Oblique sagittal gradient-echo MR imaging is a useful preoperative planning aid,
      which can predict the possibility of VA compression prior to microvascular
      decompression for hemifacial spasm.

PMID- 9755324
TI  - Cerebral blood flow velocities after subarachnoid haemorrhage in relation to the
      amount of blood clots in the initial computed tomography.
AB  - In 72 patients with acute subarachnoid haemorrhage (SAH) the relationship between
      the amount of subarachnoid blood clots detected by initial cranial computed
      tomography (CCT) up to 48 hours after bleeding and the later development of
      vasospasm, established by blood flow velocity measurement with transcranial
      Doppler ultrasound (TCD) was investigated. The serial Doppler examinations
      started within the first 72 hours after SAH and were carried out every second day
      up to three weeks. Each Doppler recording was accompanied by a neurological
      examination. Patients classified as Hunt and Hess grade V were excluded from the
      study. All patients with remarkable brain oedema in CCT or with intracranial
      pressure above 25 mmHg were also excluded. Because of the well known age
      dependence of vasospasm after SAH, two age groups were formed. A statistically
      significant correlation (p > 0.05) between blood flow velocities and blood load
      after SAH was not found. The mean age of the investigated 72 individuals was 48.9
      years (14 up to 76 years). 47 patients were younger than 56 years. Linear
      regression analysis indicated a correlation with a quite low significance level
      (r = 0.350, p < 0.025) between TCD blood flow velocities and blood load in CCT in
      these younger subjects. No significant correlation (p > 0.05) between these two
      variables could be established in the 25 patients older than 55 years. In a
      second step an intra-individual comparison of side-to-side differences in TCD and
      CCT was made. There were no significant differences in blood flow velocities
      between subjects with or without side-to-side differences in cisternal blood
      load. It is concluded that the amount of blood visible on initial CCT after SAH
      is not a powerful predictor of cerebral blood flow velocities measured by TCD.

PMID- 9755325
TI  - Thrombin activity in CSF after SAH is correlated with the degree of SAH the
      persistence of subarachnoid clot and the development of vasospasm.
AB  - We previously reported that the coagulation system in cerebrospinal fluid (CSF)
      is strongly activated in the early stage of a subarachnoid haemorrhage (SAH). We
      evaluated the relationship among thrombin activity, degree of SAH, amount of
      clearance of SAH, and vasospasm. The CSF levels of fibrinopeptide A (FPA) were
      measured by radio-immunoassay in 36 SAH patients, who were diagnosed by
      computerized tomography (CT) within 12 hours and on whom surgery was performed
      within 48 hours. Clearance of SAH (%) was evaluated as the size of the clot in
      the basal cistern visualized between the initial and postoperative CT. The mean
      level of FPA in the patients of Group 3 (Fisher's CT classification) (182.2
      ng/ml) was significantly higher than those in the patients of Group 2 (36.2
      ng/ml). There was a significant difference in the mean level of FPA between
      patients with (47.6 ng/ml) and without infarction (408.3 ng/ml). In 18 of the 27
      patients of Group 3 for whom the clearance of the SAH was determined, the
      patients showing a lower clearance rate (< 50%) of SAH demonstrated a
      significantly higher rate of infarction and a significantly higher level of FPA
      (466.6 ng/ml) than did the patients with a higher clearance rate (> 50%) of SAH
      (79.2 ng/ml). These results suggest that, the thrombin activity in CSF is
      correlated with the degree of SAH, the persistence of subarachnoid clot and the
      development of vasospasm.

PMID- 9755326
TI  - No specific brain protection against thermal stress in fever.
AB  - Knowledge about human brain temperature is still very limited, despite evidence
      demonstrating the critical influence of mild increases in temperature on the
      ischaemic brain. It has been suggested that in passive and exercise hyperthermia
      the brain may be protected against thermal damage by a mechanism of selective
      brain cooling (SBC). It is said to bring about suppression of the temperature of
      the brain, rendering it significantly lower than trunk and arterial blood
      temperature. Yet very little is known about the possible role of this mechanism
      in fever, a condition fundamentally different from "physiological" hyperthermia,
      especially when it occurs in brain-damaged patients. In our investigation we
      retrospectively analysed the results of direct recordings of cerebral temperature
      within the subdural space (Tsd) and within the brain parenchyma (Tbr-16 cases) in
      63 unanaesthetized patients following neurosurgical procedures, including 23 with
      fever > 38 degrees C. The difference between trunk temperature, measured in the
      rectum (Tre) or in the oesophagus (Tes), and the intracranial temperature, were
      calculated in all subjects. A statistically significant reduction of these
      differences, in step with increasing fever, would be compatible with
      demonstrating a process of selective brain cooling. The offsets Tre-Tsd, Tre-Tbr,
      and Tes-Tsd were plotted against Tre over a wide range of body temperature and
      near zero correlation was found. This finding suggests that brain temperature in
      fever was not selectively suppressed by any specific thermolytic mechanism and
      that dissipation of the main bulk of cerebral metabolic heat both in normothermia
      and in fever depends on heat uptake by arterial blood. The results suggest that
      the brain in fever can be seriously jeopardized by heat stress and no specific
      cooling mechanism exists, to reduce it below body temperature in feverish
      neurosurgical patients. Tbr and/or Tsd remained the highest body temperature in
      14 out of the 23 patients during fever.

PMID- 9755327
TI  - Intraoperative hypothermia and ventricular shunt infections.
AB  - Several recent studies have demonstrated a relationship between intraoperative
      hypothermia and postoperative infection. A study was therefore conducted to
      evaluate the relationship between intraoperative hypothermia and ventricular
      shunt infections. Sixty-eight children who underwent ventricular shunt placement,
      including revisions, over a six year period subsequently developed a shunt
      infection (overall shunt infection rate of 5%). Mean age was 8 years (range,
      neonate to 20 years). The last 74 children who underwent ventricular shunt
      placement without subsequent infection served as a comparison group. The
      anesthetic records of all cases were reviewed to determine the lowest core
      temperature recorded during the surgical procedure. The lowest core temperature
      varied from 33.9 degrees C to 37.7 degrees C (mean 36.0 degrees C). Hypothermia
      was defined as a temperature less than 35.1 degrees C. No relationship was found
      between hypothermia and the subsequent occurrence of a shunt infection (P =
      0.45). When those children less than 2 years old were excluded from analysis,
      there was a trend towards statistical significance (P = 0.07). In summary, this
      study failed to show any significant relationship between the occurrence of
      intraoperative hypothermia and subsequent ventriculoperitoneal shunt infection in
      a group of pediatric patients.

PMID- 9755328
TI  - Low rate of shunt revision in tumoural obstructive hydrocephalus.
AB  - The authors calculated the shunt revision rate for 77 consecutive patients with
      tumoural obstructive hydrocephalus. At a mean follow up of 23.7 months, the
      annual revision rate was 0.06 which is significantly lower than the annual
      revision rate of 0.39 for other hydrocephalic patients treated during the same
      period. Shunted patients who had total excision of their lesions had a
      significantly lower revision rate than patients who had a partial excision or a
      biopsy. It is therefore, suggested that cases with tumoural obstructive
      hydrocephalus may represent a subset of hydrocephalic patients who are associated
      with a relatively low risk of shunt complications. The observation has to be
      addressed when the role of endoscopic third ventriculostomy in these patients is
      being considered.

PMID- 9755329
TI  - Cerebral blood flow velocity and vasomotor reactivity before and after shunting
      surgery in patients with normal pressure hydrocephalus.
AB  - The purpose of this study was to evaluate pre- and post-shunting haemodynamic
      changes and their correlation with the clinical results in normal pressure
      hydrocephalus (NPH). Accordingly, eleven demented patients with clinical signs
      suggestive of NPH received examinations of cerebral blood flow velocity (BFV) and
      vasomotor reactivity (VMR) by transcranial Doppler sonography with carbogen
      testing before and after shunt treatment. Computerized tomography (CT), clinical
      assessment and neuropsychological grading were performed prior to and at 3 months
      following surgery. A control group consisting of 10 patients was included to
      establish baseline data. The pre-operative CBF studies in the anterior cerebral
      artery (ACA) and the middle cerebral artery (MCA) revealed the NPH patients did
      not have significant decreases of BFVs, but had significant decreases of carbogen
      VMR (P < 0.05). After shunting, there were no significant changes of the BFVs as
      compared with the pre-shunting data. The post-shunting VMR of the ACA was
      significantly higher than the pre-shunting one (p < 0.05), but there was no
      variation in that of the MCA. Both the values of post-shunting VMR in ACA and the
      post-shunting increase in VMR in MCA of the 7 shunt-responsive patients who
      improved mentally and in other symptoms were significantly higher than those of
      patients without improvement (p < 0.05). In addition, the five patients with gait
      improvement showed significantly higher values of post-shunting VMR of ACA and
      the post-shunting increase of VMR for both ACA and MCA when compared with those
      patients without gait improvement (p < 0.05, respectively). Our study supports
      the view that patients with NPH had various degrees of impaired VMR in both the
      ACA and the MCA, but showed insignificant reduction in BFVs, indicating a
      compensatory mechanism of CBF over time to accommodate the subnormal state of
      cerebral perfusion pressure. Shunt placement would improve the VMR in responsive
      patients. Postoperatively, an increase of VMR tends to accompany improvement of
      the functional state: that in the MCA alone is associated with symptomatic
      improvement in mental function and that increase in VMR in both the ACA and the
      MCA with improvement in gait, respectively.

PMID- 9755330
TI  - Estimation of volume doubling time and cell loss in an experimental rat glioma
      model in vivo.
AB  - We estimated the volume doubling time (Vd) of the ethyl-nitrosourea-induced rat
      glioma by serial magnetic resonance imaging, and the results were compared with
      potential doubling time (Tp) determined immunohistochemically. Vd ranged from 3.3
      to 29.2 days (11.3 +/- 7.74) and Tp ranged from 2.3 to 13.3 days (6.81 +/- 3.33).
      Each tumour showed a wide range of bromodeoxyuridine (BUdR) labelling indices
      (LI), however, Vd and Tp correlated well with BUdR-LI. Vd was estimated as 17.6 x
      BUdR-LI-0.63 (R = -0.76, P < 0.001, n = 13) and Tp was estimated as 22.6 x BUdR
      LI-1.02 (R = -0.92, P < 0.0001, n = 12). In addition, we compared the apoptotic
      indices (AI), determined by terminal deoxynucleotidyltransferase (Tdt)-mediated
      biotinylated dUTP-biotin nick-end labelling (TUNEL) techniques, with BUdR-LI and
      mitoses indices (MI). The results were: AI = 0.23 + 0.25Ln(BUdR-LI) (R = 0.971, n
      = 8, P < 0.0001) and AI = 1.05 + 0.29Ln(MI) (R = 0.937, n = 8, P < 0.001). Cell
      loss factors (CLF) also correlated well with BUdR-LI and MI. However, CLF
      calculated from Tp and Vd were lower than the values previously presumed,
      probably because of shorter Vd than true doubling time for tumour cell
      population. These results suggest that even malignant tumours retain a mechanism
      of adjusting their growth at least partly.

PMID- 9755331
TI  - Repair of dural defects in awkward areas-technical note.
AB  - Dural tears located at the base of the skull are difficult to repair due to the
      difficulties in the appropriate access and the fragility of the dura in such
      areas. In our experience the biggest problem when attempting to perform a dural
      repair in a deep narrow field is not to place the stitches, but rather to set the
      knots. A newly designed, easy-to-learn technique has been developed for dural
      closure in these situations. We present here a new technique for dural suturing
      of special interest when the space available is limited. In our hands it is
      possible to obtain a watertight dural closure in most microsurgical operations
      performed through a small hole and/or into a narrow, deep surgical field. These
      techniques can also be applied during a secondary procedure following development
      of a postoperative CSF leak. While simple and easy to learn, these techniques
      require practice in the laboratory setting before clinical application.

PMID- 9755332
TI  - A new coated bipolar coagulator: technical note.
AB  - BACKGROUND: Sometimes charring or popping occurs and the bipolar blades get stuck
      to the vessel. METHODS: The tips of one of the many commercially available
      bipolar forceps were coated in a striped manner with Teflon--50 micro in
      thickness. RESULTS: The new bipolar coagulator coated with Teflon reduced the
      incidence of tissue sticking. CONCLUSIONS: Experience with this instrument was
      still quite limited, but preliminary results were promising.

PMID- 9755333
TI  - Unusual clinical presentation of a meningeal melanocytoma with seizures: case
      report and review of the literature.
AB  - The 17th case of an intracranial meningeal melanocytoma is presented in a 67-year
      old man. It is the 6th melanocytoma arising from the cavum Meckeli and the first
      presenting with seizures. Surgical removal was curative for a follow up period of
      32 months. Besides the clinical and neuroradiological presentation, the
      histological, ultrastructural and immunohistochemical features are described. A
      review of the literature including cases with malignant transformation is given
      and differential diagnostic problems are discussed.

PMID- 9755334
TI  - Ruptured aneurysm at the bifurcation of the posterior meningeal artery from the
      proximal posterior inferior cerebellar artery.

PMID- 9755335
TI  - Turcot's syndrome presenting with medulloblastoma and familiar adenomatous
      polyposis: a case report and review of the literature.

PMID- 9755336
TI  - Internal carotid artery injury and occlusion from camel collision.

PMID- 9755338
TI  - Interleukin-12: a cytokine at the interface of inflammation and immunity.

PMID- 9755337
TI  - Biology of the interleukin-2 receptor.
AB  - Studies of the biology of the IL-2 receptor have played a major part in
      establishing several of the fundamental principles that govern our current
      understanding of immunology. Chief among these is the contribution made by
      lymphokines to regulation of the interactions among vast numbers of lymphocytes,
      comprising a number of functionally distinct lineages. These soluble mediators
      likely act locally, within the context of the microanatomic organization of the
      primary and secondary lymphoid organs, where, in combination with signals
      generated by direct membrane-membrane interactions, a wide spectrum of cell fate
      decisions is influenced. The properties of IL-2 as a T-cell growth factor spawned
      the view that IL-2 worked in vivo to promote clonal T-cell expansion during
      immune responses. Over time, this singular view has suffered from increasing
      appreciation that the biologic effects of IL-2R signals are much more complex
      than simply mediating T-cell growth: depending on the set of conditions, IL-2R
      signals may also promote cell survival, effector function, and apoptosis. These
      sometimes contradictory effects underscore the fact that a diversity of
      intracellular signaling pathways are potentially activated by IL-2R. Furthermore,
      cell fate decisions are based on the integration of multiple signals received by
      a lymphocyte from the environment; IL-2R signals can thus be regarded as one
      input to this integration process. In part because IL-2 was first identified as a
      T-cell growth factor, the major focus of investigation in IL-R2 signaling has
      been on the mechanism of mitogenic effects in cultured cell lines. Three critical
      events have been identified in the generation of the IL-2R signal for cell cycle
      progression, including heterodimerization of the cytoplasmic domains of the IL-2R
      beta and gamma(c) chains, activation of the tyrosine kinase Jak3, and
      phosphorylation of tyrosine residues on the IL-2R beta chain. These proximal
      events led to the creation of an activated receptor complex, to which various
      cytoplasmic signaling molecules are recruited and become substrates for
      regulatory enzymes (especially tyrosine kinases) that are associated with the
      receptor. One intriguing outcome of the IL-2R signaling studies performed in cell
      lines is the apparent functional redundancy of the A and H regions of IL-2R beta,
      and their corresponding downstream pathways, with respect to the proliferative
      response. Why should the receptor complex induce cell proliferation through more
      than one mechanism or pathway? One possibility is that this redundancy is an
      unusual property of cultured cell lines and that primary lymphocytes require
      signals from both the A and the H regions of IL-2R beta for optimal proliferative
      responses in vivo. An alternative possibility is that the A and H regions of IL
      2R beta are only redundant with respect to proliferation and that each region
      plays a unique and essential role in regulating other aspects of lymphocyte
      physiology. As examples, the A or H region could prove to be important for
      regulating the sensitivity of lymphocytes to AICD or for promoting the
      development of NK cells. These issues may be resolved by reconstituting IL-2R
      beta-/-mice with A-and H-deleted forms of the receptor chain and analyzing the
      effect on lymphocyte development and function in vivo. In addition to the
      redundant nature of the A and H regions, there remains a large number of
      biochemical activities mediated by the IL-2R for which no clear physiological
      role has been identified. Therefore, the circumstances are ripe for discovering
      new connections between molecular signaling events activated by the IL-2R and the
      regulation of immune physiology. Translating biochemical studies of Il-2R
      function into an understanding of how these signals regulate the immune system
      has been facilitated by the identification of natural mutations in IL-2R
      components in humans with immunodeficiency and by the generation of mice with
      targeted mutations in these gen

PMID- 9755339
TI  - Recent progress on the regulation of apoptosis by Bcl-2 family members.

PMID- 9755340
TI  - Interleukin-18: a novel cytokine that augments both innate and acquired immunity.

PMID- 9755341
TI  - CD4+ T-cell induction and effector functions: a comparison of immunity against
      soluble antigens and viral infections.

PMID- 9755342
TI  - Current views in intracellular transport: insights from studies in immunology.

PMID- 9755343
TI  - Phylogenetic emergence and molecular evolution of the immunoglobulin family.

PMID- 9755345
TI  - Characteristics of successful and unsuccessful dieters: an application of signal
      detection methodology.
AB  - Signal detection methods were used to identify predictors of successful weight
      loss in 177 mildly to moderately overweight women and men assigned to one of two
      weight-loss programs. Predictors included initial demographic, physiological,
      behavioral, and psychosocial characteristics, and program type (e.g. diet-only
      and diet-plus-exercise). Successful weight loss was defined as a loss of at least
      two units of body mass index at one year. Four subgroups were identified.
      Participants in the diet-plus-exercise program who were initially more satisfied
      with their bodies and did not have a history of repeated weight loss were most
      likely to succeed (63% succeeded). In contrast, participants assigned to the diet
      plus-exercise program who were either extremely dissatisfied with their bodies or
      who had a history of repeated weight loss were at similar risk for failure as
      participants in the diet-only program (only 26% to 35% succeeded). The results
      underscore the potential utility of exploring these subgroups further to inform
      the development of new treatment strategies to increase the likelihood of
      success.

PMID- 9755344
TI  - Current insights into the "antiphospholipid" syndrome: clinical, immunological,
      and molecular aspects.
AB  - Advances in defining the target antigen(s) for the autoantibodies in the APS
      highlight the inadequacies of the current classification of these autoantibodies
      into anticardiolipin and LA antibodies. The discovery that beta 2GPI is the
      target antigen for the autoantibodies detected in solid-phase immunoassays has
      opened a number of areas of research linking these autoantibodies to
      atherogenesis and thrombus formation. Although the role of beta 2GPI in the
      regulation of blood coagulation in unclear, current evidence suggests that anti
      beta 2GPI antibodies interfere with its "normal" role and appear to promote a
      procoagulant tendency. The expansion of research in this area and the diversity
      of the clinical manifestations of patients with APS have resulted in the
      inclusion of molecular biologists and pharmaceutical companies joining
      immunologists, hematologists, rheumatologists, obstetricians, neurologists,
      vascular surgeons, and protein and lipid biochemists in attempting to understand
      the pathophysiology of this condition. Although the published literature may
      result in conflicting results and introduce new controversies, developing
      standardized laboratory methods and extrapolation of in vitro experimental
      results to the vivo situation will advance our understanding of the regulation of
      the immune system and its interaction with normal hemostatic mechanisms. Since
      the authors' last review in 1991, the study and understanding of the
      pathophysiology of APS have evolved from lipid biochemistry to molecular
      techniques that may eventually provide specific therapies for the clinical
      manifestations of this condition. Although current treatment has improved the
      morbidity associated with this condition, especially in improving pregnancy
      outcomes, future therapies, as outlined in this review, may specifically address
      the biological abnormalities and have fewer side effects. Better diagnostic
      tools, such as magnetic resonance imaging with perfusion studies, will allow the
      study of the true incidence and prevalence of vascular flow changes/tissue
      ischemia and infarction associated with aPL antibodies and help determine
      treatment and prophylaxis for APS patients. APS is still the only hypercoagulable
      condition where both arterial and venous beds can be affected independently or in
      the same individual.

PMID- 9755346
TI  - The impact of a brief problem-solving training intervention for relatives of
      recently diagnosed breast cancer patients.
AB  - Previous studies have found high levels of psychological distress in women who
      have a family history of breast cancer. We evaluated a brief Problem-Solving
      Training (PST) intervention designed to reduce distress among women with a first
      degree relative recently diagnosed with this disease. Participants were randomly
      assigned to either the PST group (N = 144) or a General Health Counseling (GHC)
      control group (N = 197). At baseline, these groups did not differ on any
      sociodemographic, risk factor, or psychological distress variables. We evaluated
      the impact of PST, relative to GHC, at the three-month follow-up assessment using
      a 2 (treatment group) x 2 (time of assessment) mixed factor analysis of variance
      (ANOVA). Although there were significant decreases in both cancer-specific and
      general distress in both the PST and GHC groups, the magnitude of these decreases
      did not differ. However, when PST participants were divided into those who
      regularly practiced the PST techniques and those who did not, significant
      differences emerged. Participants who regularly practiced the PST techniques had
      significantly greater decreases in cancer-specific distress [Impact of Event
      Scale (IEs) intrusion and avoidance subscales] compared to infrequent practicers
      and GHC participants. Effects on general distress were not found. Additional
      studies are needed to identify ways to promote the practice of PST techniques and
      to evaluate other psychosocial interventions for female relatives of breast
      cancer patients.

PMID- 9755347
TI  - Body images and obesity risk among black females: a review of the literature.
AB  - The prevalence of obesity among Black women has reached epidemic proportions.
      Some researchers have suggested that the body images of Black females may
      contribute to their high risk for obesity by inhibiting motivation for weight
      control. While a number of empirical studies have examined the body images of
      Black females, findings are complex and at times, inconsistent. For example, some
      studies show that Black females consider overweight bodies more attractive, while
      other studies show that Black females prefer normal-weight bodies. Divergent
      findings may be due, in part, to the multidimensional nature of body image.
      Inconsistencies may also be due to differences between the Black females sampled.
      Methodological problems, including the use of measures that have been validated
      among Black females, the use of various weight-for-height standards, and the
      inconsistent analyses of or lack of physiological data, also may contribute to
      conflicting results. This review addresses the complexity of body image findings
      among a heterogeneous Black female population and the relationship between their
      body images and obesity risk. Implications for effective obesity treatment
      programs and suggestions for improvements in future body image studies are also
      discussed.

PMID- 9755348
TI  - Reliability of the timeline follow-back sexual behavior interview.
AB  - The reliability of self-reported sexual behavior is a question of utmost
      importance to human immunodeficiency virus (HIV) prevention research. The
      Timeline Follow-Back (TLFB) interview, which was developed to assess alcohol
      consumption on the event level, incorporates recall-enhancing techniques that
      result in reliable information. In this study, the TLFB interview was adapted to
      assess HIV-related sexual behaviors and their antecedents, and its reliability
      was assessed. The interview was administered to 110 participants (46% women, M
      age = 19.7; range = 18-41), and 58 participants who reported sexual behavior
      during the previous three months returned one week later for a second interview.
      Test-retest intraclass correlations (rho) from the TLFB protocol showed that all
      sexual behaviors were reported reliably (rho range = .86 to .97, median = .96).
      Bootstrapping, a nonparametric statistical technique, was used for significance
      testing in the reliability analyses. Reliability was equivalent across each of
      the three months assessed with the TLFB and was equivalent to conventional
      assessment methods (i.e. single-item questions). These findings show that the
      TLFB sexual behavior interview provides reliable reports of sexual behavior over
      three months and yields event-level data that are extremely valuable for sexual
      behavior and HIV-prevention research.

PMID- 9755349
TI  - The effect of pain on memory for affective words.
AB  - Memory is a key cognitive variable in pain management, but lacks extensive
      research. This study is a replication and extension of Seltzer and Yarczower's
      investigation of pain's influence on memory for affective words, which found
      fewer positive words and more negative words recalled if subjects were in acute
      pain (versus no pain). In the present study, two experiments were conducted: one
      with a recall memory test and one with a recognition memory test. One hundred
      sixty undergraduate subjects were randomly placed in one of four groups: two
      groups had the same condition (pain or no pain) for both the encoding task and
      memory test, and two groups had mixed conditions (pain at encoding-no pain at
      memory test or no pain at encoding-pain at memory test). Pain was induced by 0
      degrees-2 degrees C water immersion. At encoding, subjects categorized words by
      judging them as either positive or negative. Results of both experiments show
      that pain impairs memory. In neither experiment were differences found on memory
      for positive and negative words. These results do not support Seltzer and
      Yarczower's discriminative effects of pain on word category, but they are
      consistent with other research using acute pain manipulations and chronic pain
      populations, suggesting that pain interferes with memory. It is hypothesized that
      pain depletes scarce attentional resources, thereby interfering with concurrent
      cognitive tasks such as thinking, reasoning, and remembering.

PMID- 9755350
TI  - Compliance with inhaled medications: the relationship between diary and
      electronic monitor.
AB  - Self-report is a frequently-used method of assessing compliance with prescribed
      medications in patients with chronic illnesses. Most researchers agree, however,
      that self-report misrepresents patient adherence to regimen prescription. In this
      randomized, controlled study evaluating inhaler medication compliance, diary data
      was compared to electronic monitoring in 55 adults with asthma. Subjects
      randomized to the treatment group received a six-week self-management program. An
      electronic monitor, the MDI Chronolog, was used in this study to assess inhaler
      use. The MDI Chronolog records the date and time of each inhaled activation. The
      self-report measure used was a daily asthma diary. Subjects were asked to use
      their inhaled medications as usual and record the date and time they administered
      their medication over a one-week period. Moderate correlations (rs = .55, Mdnd =
      95.8, Mdnc = 91.6) were found when comparing the number of administrations
      calculated using the MDI Chronolog to the number of administrations reported in
      the subject's diary. When the dosing interval was examined, however, the
      correlation was weaker (rs = .44, Mdndiary = 92.8, Mdnchronolog = 37.5). In each
      case, self-reported compliance was higher than monitored adherence.

PMID- 9755351
TI  - Effects of preparatory videotapes on self-efficacy beliefs and recovery from
      coronary bypass surgery.
AB  - This study evaluated the relative effects of three experimental videotapes that
      involved different approaches for preparing coronary artery bypass graft (CABG)
      patients for surgery and the inhospital recovery period. One of the tapes
      conveyed information via a health care expert only. The other two featured the
      same health care expert and also included clips of interviews with patient
      models. These latter two tapes differed in the extent to which they portrayed the
      recovery period as a steady, forward progression or as consisting of "ups and
      downs". Two hundred fifty-eight male CABG patients were randomly assigned to view
      one of the three videotapes on the evening prior to surgery or to a control
      condition. Overall, patients who viewed any of the videotapes felt significantly
      better prepared for the recovery period, reported higher self-efficacy for using
      the incentive spirometer and for speeding their recovery, performed more
      repetitions with their incentive spirometer each time they used it
      postoperatively, had shorter intensive care unit stays, and were released from
      the hospital more quickly than patients in the control condition. There was also
      evidence that patients' self-efficacy beliefs for speeding recovery directly
      mediated the effects of the videotapes on length of stay both in the intensive
      care unit and in the hospital.

PMID- 9755352
TI  - Serotonin: how much we have learned! So much to discover...

PMID- 9755353
TI  - Possible serotonergic mechanisms underlying the antidepressant and anti-obsessive
      compulsive disorder responses.
AB  - Considerable evidence is now available to support the pivotal role of the
      serotonin (5-HT) system is exerting the antidepressant response in humans.
      Different type of antidepressant treatments enhance 5-HT neurotransmission via
      different pre- or postsynaptic mechanisms. The time course for the occurrence of
      these adaptive changes in the brain of laboratory animals is consistent with the
      delayed onset of the antidepressant response in humans. The drugs effective in
      obsessive-compulsive disorder (OCD) also enhance 5-HT neurotransmission in brain
      regions involved in mediating OCD symptoms but with a more prolonged delay,
      consistently with the larger time necessary to obtain therapeutic effect in OCD
      than in depression. The elucidation of these mechanisms of action lead to the
      development of new pharmacologic strategies to potentiate the therapeutic effect
      of the drugs currently available and the identification of novel targets to
      accelerate and further improve treatment response in depression and OCD.

PMID- 9755354
TI  - Novel therapeutic approaches beyond the serotonin receptor.
AB  - The influence of serotonin (5-HT) on neuronal function is mediated by regulation
      of receptor-coupled intracellular signal transduction pathways, and the
      therapeutic action of 5-HT selective reuptake inhibitors (SSRIs), as well as
      other types of antidepressants, most likely involves regulation of these
      intracellular pathways. The cyclic adenosine monophosphate (cAMP) second
      messenger system is one pathway that could be involved in antidepressant action.
      Chronic administration of antidepressants, including SSRIs, up-regulates the cAMP
      pathway at several levels, including increased expression of the cAMP response
      element binding protein (CREB). Among the multiple target genes that could be
      regulated by CREB and that could be involved in antidepressant actions and the
      pathophysiology of depression in brain-derived neurotrophic factor (BDNF). Stress
      decreases the expression of BDNF, and reduce levels of this neurotrophic factor
      could contribute to the atrophy and decreased function of stress-vulnerable
      hippocampal neurons. In contrast, antidepressant treatment increases the
      expression of BDNF in hippocampus, and could thereby reverse the stress-induced
      atrophy of neurons or protect these neurons from further damage. Up-regulation of
      the cAMP and BDNF systems has resulted in a novel model for the mechanism of
      action of antidepressants and new targets for the development of therapeutic
      agents.

PMID- 9755355
TI  - Child and adolescent mood disorders--experience with serotonin-based therapies.
AB  - By most measures, child and adolescent depression is much like and continuous
      with adult depression. Aggregating all available data, much of which is
      relatively new, it seems most likely that noradrenergic and mixed
      serotonergic/noradrenergic tricyclic antidepressants are ineffective in child and
      adolescent depression, whereas serotonergic antidepressants (e.g., selective
      serotonin reuptake inhibitors) are probably effective).

PMID- 9755356
TI  - Serotonergic synergism: the risks and benefits of combining the selective
      serotonin reuptake inhibitors with other serotonergic drugs.
AB  - It has become common clinical practice to combine the selective serotonin
      reuptake inhibitors with other serotonergic agents for augmentation or adjunctive
      purposes. The empirical basis for using these combinations remains limited, but
      is growing. Also growing is a literature that suggests that even the most
      apparently benign combinations of serotonergic drugs carry at least some risk of
      serious pharmacokinetic or pharmacodynamic drug interactions, such as a serotonin
      syndrome.

PMID- 9755357
TI  - Implications of failing to achieve successful long-term maintenance treatment of
      recurrent unipolar major depression.
AB  - This is a review article that describes current data, issues, and controversies
      regarding long-term maintenance treatment of depression. The authors suggest that
      the issues represent a public health crisis. This paper will identify the need,
      from both a health-care and economic perspective, for more research on the
      efficacy of maintenance treatment for this pernicious and lifelong disorder. Data
      will be reviewed on the natural course of unipolar depression, focusing on
      clinical predictors that increase the risk of a relapse or recurrence. This
      review will include new data from the National Institute of Mental Health
      Collaborative Depression Study. Failing to achieve adequate maintenance treatment
      for unipolar recurrent major depression has psychopathological and psychosocial
      consequences, decreasing work productivity and the quality of a person's life.
      Published double-blind placebo-controlled studies on continuation treatment of
      major depression will be reviewed. The two competed double-blind placebo
      controlled long-term maintenance studies of recurrent unipolar major depression
      will be discussed in detail. Despite the positive findings from research done to
      date, there remain many unresolved questions relating to the maintenance
      treatment of recurrent unipolar major depression, and the need for research in
      this area is critical. The paper concludes with recommendations for long-term
      maintenance treatment of unipolar major depression.

PMID- 9755358
TI  - MN blood groups and bipolar disorder: evidence of genotypic association and Hardy
      Weinberg disequilibrium.
AB  - BACKGROUND: MN blood groups have been studied in the past as a genetic marker of
      biopolar disorder (BD). Several previous studies reported an association of the
      illness with lower frequency of blood group NN. METHODS: We analyzed distribution
      of MN blood groups in a sample of 174 patients with BD, 176 with unipolar
      depression, 98 with schizophrenia, and 331 healthy controls. In addition, we
      tested whether the inferred genotypes. conform to Hardy-Weinberg equilibrium
      (HWE). RESULTS: The frequency of NN phenotype was significantly lower among the
      bipolar patients than in any of the other three groups (p < .001). The genotype
      frequencies in the BD group deviated significantly from those expected under HWE
      (p < .01). CONCLUSIONS: These results suggest a possible locus on chromosome 4
      (4q28-q31.1) associated with genetic susceptibility to bipolar illness.

PMID- 9755359
TI  - The role of the beta-noradrenergic system in cholecystokinin-tetrapeptide-induced
      panic symptoms.
AB  - BACKGROUND: The authors determined whether effective beta-adrenergic blockade
      could attenuate the panicogenic effects of cholecystokinin-tetrapeptide (CCK-4)
      in healthy volunteers. METHODS: Subjects were randomly assigned to either a
      propranolol (n = 14) or placebo (n = 16) infusion. Ten minutes after completion
      of the infusion subjects received a bolus injection of CCK-4 (50 micrograms).
      RESULTS: Acute pretreatment with propranolol was more effective than placebo in
      decreasing behavioral and cardiovascular sensitivity. CONCLUSIONS: These
      preliminary results suggest that the panicogenic effects of CCK-4 are mediated,
      in part, through the beta-adrenergic system.

PMID- 9755360
TI  - Effects of meta-chlorophenylpiperazine on cerebral blood flow in obsessive
      compulsive disorder and controls.
AB  - BACKGROUND: A number of studies have shown that the serotonin receptor agonist
      meta-chlorophenylpiperazine (mCPP) can exacerbate symptoms in patients with
      obsessive-compulsive disorder (OCD). The aim of the present study was to study
      the effect of this compound on regional cerebral blood flow (rCBF) in patients
      and controls. METHODS: Seven OCD patients and 8 healthy controls were randomly
      allocated to a double-blind challenge study with mCPP (0.5 mg/kg orally). rCBF
      was measured by 99m-Tc-hexamethyl-propyleneamineoxime single photon emission
      computed tomography. RESULTS: mCPP did not induce OCD symptoms in patients, but
      caused a significant decrease in rCBF in OCD patients, but not in controls. The
      decrease was seen in the reference regions cerebellum and whole brain, and in the
      frontal cortex, caudate nucleus, putamen, and thalamus. CONCLUSIONS: The effect
      of mCPP on the reference regions in patients posed methodological problems in the
      normalization methods. A possible role of the cerebellum in OCD is discussed.

PMID- 9755361
TI  - No mitochondrial haplotype was found to increase risk for Alzheimer's disease.
AB  - BACKGROUND: Seventy Alzheimer's disease (AD) patients and 80 age- and sex-matched
      controls were analyzed for mitochondrial mutations T4336C and A3397G, reported to
      be associated with AD, and for mutations T4216C/G13708A characteristic for a
      normal human haplotype associated with increased frequency of occurrence of some
      hereditary diseases. The distribution of apolipoprotein E (apoE) alleles was also
      analyzed. METHODS: Mitochondrial DNA was amplified by polymerase chain reaction,
      and the presence of mutations was detected by digestion with approximately chosen
      restriction endonucleases (restriction fragment length polymorphism). RESULTS:
      One patient and 2 controls were found to belong to the T4336C/T1630C haplotype.
      No A3397G mutant was detected. The T4216C/G13708A haplotype occurred at 5/70 and
      5/80 frequency in the two groups. Prevalence of the apoE4 allele was
      significantly higher in AD patients (25%) than in the control group (8.1%).
      CONCLUSIONS: The T4336C/T16304C mutations were not found to associated with AD,
      and no predisposing mitochondrial haplotypes were found.

PMID- 9755362
TI  - Sexual dysfunction and selective serotonin reuptake inhibitors.

PMID- 9755363
TI  - Dual relation between leptin and cortisol in humans is disturbed in Alzheimer's
      disease.

PMID- 9755366
TI  - Performance of healthy adults versus individuals with brain injuries on the
      supplemental measures of the WAIS-R NI.
AB  - The Wechsler Adult Intelligence Scale-Revised as a Neuropsychological Instrument
      (WAIS-R NI) provides methods to uniformly interpret atypical responses or
      response patterns. To date, little research has examined the primary population
      for which the supplemental measures of the WAIS-R NI were intended. The purpose
      of the present study was to compare the performance of individuals with brain
      injuries versus healthy adults on the supplemental measures of the WAIS-R NI.
      Forty-nine healthy adults and 45 individuals with brain injuries were tested.
      MANOVA indicated a significant main effect for group membership and the results
      suggest the WAIS-R NI supplemental measures differentiate individuals with brain
      injuries from healthy adults.

PMID- 9755365
TI  - Depression after traumatic brain injury: conceptualization and treatment
      considerations.
AB  - The understanding and treatment of depression that develops following traumatic
      brain injury (TBI) is still unclear and likely to be the result of a complex
      variety of interacting factors. Past researchers have developed ways to classify
      important variables related to patients' depression into broad domains such as:
      Pre-injury assets and liabilities, the nature and severity of brain injury; and
      reaction to difficulties. However, a better conceptualization of the problem is
      required in order to guide the assessment and treatment considerations for
      depressed patients with TBI. This review provides this conceptualization by
      postulating six theoretical relationships between depression and TBI. The degree
      of empirical support provided in the literature for these links is indicated.
      Research findings suggested that an individual with TBI is the most susceptible
      to depression when any of the following conditions exist: a pre-existing
      psychiatric disturbance is exacerbated; the injury sustained involved the left
      anterior region of the brain; and when her individual has poor insight into her
      deficits, attempts to resume her pre-injury roles and experiences significant
      failure. For each relationship, a likely outcome is predicted if the recommended
      treatment plan is not conducted. The present conceptualization and treatment
      considerations will be of substantial benefit to clinicians working in the area.

PMID- 9755364
TI  - Blood alcohol level and early cognitive status after traumatic brain injury.
AB  - STATEMENT OF PURPOSE: This archival study sought to clarify the relationship
      between admission blood alcohol level (BAL) after traumatic brain injury (TBI)
      and subsequent neuropsychological functioning. It was hypothesized that BAL would
      be positively correlated with impairment on basic neuropsychological tests and
      that this relation would weaken as time since TBI increased. METHODS: Fifty-eight
      patients were tested within 60 days of their TBI. Correlational analyses were
      used to test the relation between neuropsychological performance and admission
      BAL. RESULTS: As expected, BAL was unrelated to demographic variables or lag time
      between TBI and time of testing, Bivariate correlations showed that higher BAL
      predicted poorer performance on a broad range of neuropsychological tests.
      Patients tested less than 30 days after their TBI showed the strongest effects.
      CONCLUSIONS: Neuropsychological impairments detected 1-2 months after TBI may be
      affected by BAL at the time of hospital admission. The influence of BAL seems
      greatest during the first month post-injury, but may persist beyond 30 days in
      some areas of cognitive function. Blood alcohol at the time of injury may have a
      direct effect on cognitive functioning or may be a proxy for the effects of
      chronic alcohol use or abuse. Clinical implications are discussed.

PMID- 9755367
TI  - Spontaneous complaints of long-term traumatic brain injured subjects and their
      close relatives.
AB  - Long-term consequences of head injury for patients and families are not well
      known, given the complexity of variables that have to be studied. Subject's self
      experience is one of these less studied aspects. The purpose of this study is to
      examine the spontaneous complaints of long-term brain injured adult subjects to
      be compared to the impression of their relatives. A total of 48 chronic head
      trauma subjects were studied more than 6 years after injury together with a
      relative, usually a mother or wife. At the beginning of the interview the
      participants were asked to freely refer their present complaints. In general,
      relatives referred more complaints about the injured subjects than the injured
      subjects referred about themselves. This occurred in several domains: somatic,
      physical, cognitive, and behavioural. Memory problems were highly reported by
      both groups. Somatic complaints were more frequently reported by patients and
      behavioural problems were more often reported by relatives. Mothers and wives had
      different profiles or responses. Mothers' opinions were identical to those of
      their TBI sons in all domains. These different results must be taken into
      consideration so that the real needs of patients and relatives can be addressed.

PMID- 9755368
TI  - Competence in discourse as a measure of social integration and quality of life in
      persons with traumatic brain injury.
AB  - Persisting difficulties in communication are a serious handicap faced by many
      after traumatic brain injury (TBI) and a major barrier to community
      reintegration. Conventional approaches to the study of communication problems
      after TBI have focused on the form of language production and expression, usually
      in terms of phonological, semantic, and syntactical features. Most TBI patients,
      however, perform overall within normal ranges on these conventional indicators.
      More recently, attention has focused on language in its naturally-occurring form,
      that is, discourse, which is heavily influenced by linguistic, cognitive and
      social skills. Because most TBI patients are left with residual deficits in these
      areas, study of discourse abilities seem to be particularly suited to
      understanding their problems in communication and facilitating eventual
      reintegration into the community. This study was designed to determine if and how
      the conversational discourse of TBI patients differs from a matched non-TBI group
      and whether any identified variables are related to measures of outcome as
      measured by community integration and quality of life. Additionally, the study
      was designed to explore the relationship between TBI and features of discourse
      across conversational, narrative, procedural genres. TBI patients (n = 30) from
      an out-patient brain injury programme were compared to matched controls (n = 10)
      in the three discourse genres. Bivariate and multivariate analyses evaluated 23
      measures of discourse efficiency, complexity, topic management, information and
      pragmatic behaviours in each genre as well as measures of psychosocial
      adjustment, particularly social integration and quality of life. Results
      indicated that TBIs were significantly different from controls on several
      measures of discourse and psychosocial adjustment. A number of other features of
      discourse were found to correlate significantly with social integration and
      quality of life. Interestingly, discourse variables appeared to correlate with
      social integration more strongly than age, gender, education, and other
      conventional psychosocial factors. Contrary to prediction, features of
      conversational discourse did not correlate more strongly than other types of
      discourse with social integration and quality of life. Discussion centred on the
      apparent comorbidity of features in everyday discourse and psychosocial
      determinants that were associated with quality of life and social integration.

PMID- 9755369
TI  - Effects of mild traumatic brain injury on narrative discourse production.
AB  - Mild traumatic brain injury (MTBI) and postconcussive syndrome can result in
      difficult to document complaints regarding subtle language use. Narrative
      discourse production has been shown to be a sensitive index of linguistic and
      cognitive deficits in the more severe TBI population. The narrative discourse
      production of MTBI subjects was investigated to determine whether cognitive
      changes were reflected in linguistic production. Eight MTBI, five moderate TBI,
      and five neurologically normal subjects were matched for age, education, and
      gender. The TBI subjects were matched on a number of neuropsychological measures.
      The subjects produced narratives about their correct picture sequences on five
      items from the Wechsler Adult Intelligence Scale-Revised picture arrangement
      subtest. The narratives were scored for correct arrangement, content essential
      information, correct story, and implied meaning. Significant differences were
      found between the normal control group and both the TBI groups on accuracy of
      narrative description of the correct picture sequences. Although differences in
      generation of implied meaning failed to reach significance, a trend was noted for
      both the TBI groups to produce fewer implied meanings than the control group. The
      results suggest that cognitive disruptions associated with MTBI may affect the
      quality of narrative discourse.

PMID- 9755370
TI  - Auditory vs visual speech timing cues as external rate control to enhance verbal
      intelligibility in mixed spastic-ataxic dysarthric speakers: a pilot study.
AB  - Metronome, singing, and board pacing were used as external rate control
      techniques for the purpose of comparing the effectiveness of auditory and visual
      speech timing cues for reducing speech rate and increasing intelligibility in
      three traumatically brain injured mixed spastic-ataxic dysarthric speakers. A
      single system design with baseline reversal (ABACAD) was used in this preliminary
      investigation. Results demonstrated statistically significant (p < 0.05) changes
      in increased speech intelligibility during all three pacing conditions for the
      two more involved subjects. Differences between treatment conditions were not
      statistically significant. However, auditory metronome cuing showed the best
      results for the two subjects who benefited from rate control. Lower baseline
      intelligibility was strongly correlated with higher benefit from rate control.
      Furthermore, the two auditory rhythmic pacing conditions exhibited a close
      synthronization effect between the frequency rate of the cue and speech rate.
      Significant correlation coefficients between decreased speech rate and increased
      intelligibility were only found for the two more involved subjects. These
      findings suggested a differential benefit of slowing speech rate to improve
      intelligibility contingent upon severity of speech deficits.

PMID- 9755371
TI  - Female TBI patients recover better than males.
AB  - The purpose of the present study was to look at possible gender differences in
      outcome after severe traumatic brain injury. Three hundred and thirty four
      consecutive patients, 72 females and 262 males, age range 5-65 years, were
      included in the study. Age range and severity of injury, evaluated by duration of
      unconsciousness, did not differ between male and female patients. Predicted
      outcome at the time of discharge from an in-patient rehabilitation programme was
      evaluated according to work capacity. Female TBI patients had a better predicted
      outcome (p < 0.015). It is suggested that progesterone, acting as a
      neuroprotective agent, may explain this difference in outcome.

PMID- 9755372
TI  - The snail companies. Neurex Corporation & Cognetix Inc.

PMID- 9755373
TI  - Show me the money.

PMID- 9755374
TI  - [10 years of Fraxiparin. Milestones in the prophylaxis of thromboembolism].

PMID- 9755376
TI  - Meaningful quotations from Paul Dudley White.

PMID- 9755375
TI  - Viagra, the latest cardio-VASCULAR drug.

PMID- 9755377
TI  - Potential cardiovascular applications of glutamate, aspartate, and other amino
      acids.
AB  - Cardioplegic solutions rich in the hydrophilic, basic amino acids, glutamate and
      aspartate, have enhanced myocardial preservation and left ventricular function.
      This has been demonstrated in assorted animal preparations involving ischemia
      with and without reperfusion. Published clinical data, though limited, strongly
      support the contention that these amino acids have myocardial protective
      properties. Several biochemical mechanisms exist by which certain amino acids may
      attenuate ischemic or reperfusion injury. Glutamate and aspartate may become
      preferred myocardial fuels in the setting of ischemia. They may also reduce
      myocardial ammonia production and reduce cytoplasmic lactate levels, thereby
      deinhibiting glycolysis. Some amino acids may become substrate for the citric
      acid cycle. Glutamate and aspartate also move reducing equivalents from cytoplasm
      to mitochondria where they are necessary for oxidative phosphorylation and energy
      generation. A rationale exists for the use of an amino acid-rich cardioplegia
      like solution in myocardial infarction. These solutions are safe and inexpensive.

PMID- 9755378
TI  - Acute ischemic syndromes following coronary artery bypass graft surgery.
AB  - Coronary artery bypass graft (CABG) surgery, performed for the control of angina
      pectoris, leads to postoperative relief from symptoms in most patients.
      Amelioration of ischemia and improvement in exercise capacity after CABG are well
      documented. However, patients currently undergoing CABG are more complex than in
      the past--they are older and are maintained on medical therapy for longer
      periods. A large number of these patients have had one or more previous
      myocardial revascularization procedures. The post-operative period would appear
      to be a time of vulnerability for coronary events. However, previous
      investigators have focused on the pre- and intraoperative aspects of peri-CABG
      ischemia. Outcome data suggest that the postoperative interval is at least
      equally important as a determinant of short- and long-term morbidity and
      mortality. We discuss the epidemiology, etiology, pathophysiology, and treatment
      of ischemic syndromes in the postoperative period after CABG. In addition, we
      review recent data from a series of 14 patients, observed at our institution, who
      underwent cardiac catheterization and, in some cases, angioplasty of the culprit
      vessel in the immediate postoperative period.

PMID- 9755379
TI  - Verapamil use in patients with cardiovascular disease: an overview of randomized
      trials.
AB  - BACKGROUND: Several reports have questioned the lack of safety data on calcium
      antagonists as a drug class. Because this drug class is heterogeneous, unique
      features of certain calcium antagonists may set them apart in terms of safety and
      efficacy. HYPOTHESIS: With in excess of 7,000 person-years of observation from
      randomized clinical trials, verapamil was selected to evaluate whether there was
      evidence of harm in patients with cardiovascular disease. METHODS: MEDLINE search
      of English-language articles, Science Citation Index, Current Contents, manual
      review of cited references, pharmaceutical files, and investigator correspondence
      was performed. Independent review of 66 articles identified 14 randomized,
      parallel-group studies for inclusion. Independent, duplicate assessments were
      made of patient outcomes and trial characteristics (including study design,
      treatment dosage and schedule, duration of treatment, inclusion criteria, and
      sample size). Standard meta-analytic techniques were employed for analysis and
      interpretation of results. RESULTS: Based on over 4,000 person-years of
      observation, patients with acute myocardial infarction (MI) treated with
      verapamil had a decreased risk of nonfatal reinfarction compared with placebo
      (relative risk 0.79; 2-sided 95% confidence interval 0.65.0.97; p = 0.024).
      Verapamil had no significant effect on overall mortality compared with placebo
      (relative risk ranged from 0.93; 2-sided 95% confidence interval 0.78, 1.10; p =
      0.40 to 0.86; 2-sided 95% confidence interval 0.71, 1.04; p = 0.13) depending on
      rules used to include or exclude patients from the pooling process. For the
      combined outcome of death or reinfarction, verapamil use was associated with a
      decreased risk compared with placebo (relative risk 0.82; 2-sided 95% confidence
      interval 0.70, 0.97; p = 0.016). In patients with angina involving a wide
      spectrum of disease severity, data were limited to 2,900 person-years of
      observation, and verapamil use did not appear to be associated with an apparent
      effect on mortality or MI. Data available from randomized studies of verapamil in
      patients with hypertension were too limited to reach conclusions (50 person-years
      of observation, with no deaths or MIs reported). Subgroups of hypertensive
      patients in two of the largest post-MI studies and the largest angina study,
      involving over 600 patients, yielded little useful added information.
      CONCLUSIONS: In patients with MI, the risks of both nonfatal reinfarction and the
      combined outcome of death or nonfatal MI were reduced over intermediate-term
      follow-up among patients treated with verapamil compared with controls (p = 0.024
      and p = 0.016, respectively). In patients with angina, no evidence for harm was
      noted, but in hypertension the data were too limited to draw conclusions. These
      findings support the need to distinguish among different calcium antagonist
      compounds and to emphasize the need for more data in patients with hypertension.

PMID- 9755381
TI  - Maximizing the hemodynamic benefit of enhanced external counterpulsation.
AB  - BACKGROUND: Enhanced external counterpulsation (EECP) has been demonstrated to be
      an effective treatment for angina and exertional ischemia in patients with
      coronary disease. HYPOTHESIS: It is hypothesized that the ability of EECP to
      enhance the recruitment or development of coronary collaterals in coronary artery
      disease may be determined by the relative magnitude of diastolic augmentation
      (DA) and systolic unloading (SU). This study examines the relation between the
      proposed EECP effectiveness ratio (DA/SU), as assessed by finger plethysmography,
      and changes in descending aortic flow as assessed by Doppler echocardiography in
      15 patients during EECP. METHODS: Varying external cuff pressures (0-275 mmHg)
      were used to generate a range of DA/SU ratios. The effect on aortic antegrade
      systolic and retrograde diastolic flow was assessed by Doppler echocardiography
      to determine whether there was an optimal EECP effectiveness ratio that maximizes
      the hemodynamic effects of EECP. With increasing DA/SU there was an initial
      positive linear increase in both systolic and diastolic flow volume. Systolic
      flow maximized at an effectiveness ratio of 1.5 and diastolic flow at a ratio of
      2.0 RESULT: Therefore, effectiveness ratios (DA/SU) in the range of 1.5-2.0 are
      optimal for maximizing the hemodynamic effects of EECP.

PMID- 9755380
TI  - A comparative study of eccentric and concentric coronary stenosis vasomotion in
      patients with Prinzmental's variant angina and patients with stable angina
      pectoris.
AB  - BACKGROUND AND HYPOTHESIS: In patients with stable angina pectoris, eccentric
      stenoses have a greater potential for dynamic changes of caliber in response to
      vasoactive stimuli than concentric lesions. It is not known whether in patients
      with coronary artery spasm the degree of coronary vasoconstriction differs in
      eccentric versus concentric stenoses. Therefore, we examined the relationship
      between coronary stenosis morphology and the vasomotor response to vasoactive
      stimuli in patients with variant angina. METHODS: Computerized quantitative
      angiography was used to measure minimum luminal diameter of eccentric and
      concentric stenoses before and after the administration of ergonovine and
      isosorbide dinitrate in 22 patients with Prinzmetal's variant angina and in 20
      patients with chronic stable angina. RESULTS: In patients with variant angina,
      mean stenosis diameter reduction with ergonovine was -0.85 +/- 0.38 and -1.12 +/-
      0.69 mm in eccentric and concentric stenoses, respectively (p = NS). Isosorbide
      dinitrate promptly relieved spasm in all patients and increased the diameter of
      eccentric stenoses by 0.26 +/- 0.34 mm and that of concentric stenoses by 0.24 +/
      0.32 mm (p = NS). In patients with chronic stable angina, mean diameter
      reduction with ergonovine was -0.23 +/- 0.12 and -0.12 +/- 0.10 mm for eccentric
      and concentric stenoses, respectively (p < 0.05). Isosorbide dinitrate increased
      coronary diameter by 10% from baseline in 70% of eccentric and 38% of concentric
      stenoses (p < 0.01). CONCLUSION: In patients with variant angina pectoris,
      eccentric and concentric spastic stenoses react similarly in response to
      vasoactive stimuli. In patients with chronic stable angina, eccentric stenoses
      are more likely to show vasomotor responses than concentric stenoses.

PMID- 9755382
TI  - Serum amyloid type A may be a predictor of restenosis.
AB  - BACKGROUND: Elevation of acute phase proteins [C-reactive protein (CRP) and serum
      amyloid type A (SAA)] has been demonstrated in unstable angina with an adverse
      clinical prognosis. HYPOTHESIS: The study was undertaken to determine the effect
      of angioplasty on the levels of SAA and the correlation with postangioplasty
      restenosis. METHODS: In a university-affiliated tertiary medical center, a
      prospective case study was undertaken in 55 patients who underwent successful
      percutaneous transluminal coronary angioplasty (PTCA) of a single coronary lesion
      for angina pectoris. Three groups of patients were clinically characterized
      according to Braunwald's classification of anginal syndrome: Group A: class III;
      Group B: class I; Group C: stable angina. Serum amyloid type A was measured by an
      ELISA method before PTCA and after 24 h, 1, and 3 months. Patients were followed
      clinically for 12 months. A thallium stress perfusion scan was performed 3 months
      after PTCA and coronary angiography was repeated in patients with an abnormal
      thallium perfusion scan. RESULTS: Serum amyloid type A levels > 100 micrograms/ml
      could identify Group A patients with a high sensitivity and specificity (r = 0.85
      and 0.86, respectively). Of the patients studied, 75% increased their SAA level
      24 h after angioplasty. An increase of SAA by > 100% was associated with an
      increased risk of restenosis, with a relative risk of 6.4 (p < 0.05). CONCLUSION:
      Increased levels of SAA characterize patients with unstable angina pectoris with
      a high specificity and sensitivity. Levels of SAA that increase > 100% 24 h after
      angioplasty may serve as a marker of restenosis.

PMID- 9755383
TI  - Treatment of severe mitral stenosis with percutaneous balloon valvotomy in
      pregnant patients.
AB  - BACKGROUND: Pregnancy can cause life-threatening complications in women with
      mitral stenosis. Frequently, there is an urgent need to increase the mitral valve
      area mechanically. In selected cases, percutaneous mitral balloon valvotomy
      (PMBV) has emerged as a safe and effective alternative to surgical
      commissurotomy. HYPOTHESIS: The study evaluates the effects of PMBV by the Inoue
      technique in nine pregnant patients with severe symptomatic mitral stenosis.
      METHODS: The patients were in New York Heart Association (NYHA) functional class
      II to IV and had echocardiographic scores of < or = 8. The mean gestational age
      was 24.8 +/- 6.1 weeks. The patient's pelvic and abdominal regions were covered
      with a lead apron to protect the fetus from radiation. A stepwise dilatation
      technique was used. Fluoroscopy time was kept to 10 to 15 min. RESULTS: One
      patient developed severe mitral regurgitation requiring emergency valve
      replacement. The remaining eight patients showed marked immediate symptomatic and
      hemodynamic improvement. After dilatation, the transmitral pressure gradient
      decreased from 20.8 +/- 6.5 to 7.3 +/- 1.4 mmHg (p = 0.001) and the calculated
      mitral valve area increased from 0.9 +/- 0.1 to 1.8 +/- 0.4 (p < 0.001). All
      patients had uneventful term deliveries of normal babies. On follow-up they were
      in NYHA functional class I. CONCLUSIONS: Percutaneous mitral balloon valvotomy is
      a safe and effective procedure for selected pregnant patients with severe mitral
      stenosis. The procedure is well tolerated by the fetus. Severe mitral
      regurgitation requiring immediate surgery may occur occasionally. The possible
      harmful effects to the fetus from its exposure to radiation during PMBV are
      unknown.

PMID- 9755384
TI  - Comparison of epirubicin and doxorubicin cardiotoxicity induced by low doses:
      evolution of the diastolic and systolic parameters studied by radionuclide
      angiography.
AB  - BACKGROUND: Previous studies have demonstrated that epirubicin (EPI) has a lower
      propensity to produce cardiotoxic effects than doxorubicin (DXR) at high doses.
      HYPOTHESIS: The aim of the study was to compare the cardiotoxicity induced by low
      doses of EPI and DXR in patients before and 1 month after the end of
      chemotherapy. METHOD: In a prospective study, 99 patients with a mean age of 51
      +/- 12 years and without cardiac disease were studied before and 1 month after
      the end of chemotherapy. Group 1 included 38 patients receiving 246 +/- 96 mg/m2
      of DXR and Group 2 included 61 patients receiving EPI with and equivalent dose of
      219 +/- 92 mg/m2 of DXR. Ejection fraction (EF) of the left ventricle (LV), peak
      ejection rate (PER), and peak filling rate (PFR) [expressed in end-diastolic
      volume/s (EDV/s)] were evaluated by gated radionuclide angiography; PFR/PER were
      also calculated. RESULTS: Moderate and similar alterations of left ventricular
      ejection fraction were shown for low doses of anthracyclines. The EF of the LV
      decreased from 57 +/- 6% to 54 +/- 6% for DXR group (Group 1) (p = 0.005), and
      from 58 +/- 5% to 55 +/- 5% for the EPI group (Group 2)(p = 0.001). The PER of
      the left ventricle fell from 3.08 +/- 0.46 EDV/s to 2.79 +/- 0.49 in Group 1 (p =
      0.004) and from 2.98 +/- 0.50 to 2.73 +/- 0.34 EDV/s in Group 2 (p = 0.001). In
      contrast, no significant alteration of PFR appeared in Group 2 (from 2.72 +/-
      0.51 to 2.62 +/- 0.41 EDV/s) for the equivalent dose of anthracycline, while PFR
      of the LV dropped from 2.82 +/- 0.76 (EDV/s) to 2.41 +/- 0.55 after doxorubicin
      (p = 0.004). No difference was found between 1 and 12 months after the end of the
      treatment in 25 patients in Group 1 and 28 patients in Group 2. These results
      confirm the advantage of EPI over DXR in terms of cardiotoxicity and help explain
      the relationship of cellular damage mechanisms with the functional parameters of
      nuclear investigation. CONCLUSION: A possible explanation for specific alteration
      after DXR could be the increased production of semiquinone free radicals, which
      are known to induce membrane damage and, consequently, myocardial edema and
      diastolic alteration.

PMID- 9755385
TI  - Symmetric and asymmetric left ventricular hypertrophy in patients with end-stage
      renal failure on long-term hemodialysis.
AB  - BACKGROUND: Patients with end-stage renal disease on regular hemodialysis have an
      increased prevalence of left ventricular (LV) hypertrophy that is associated with
      morbidity and mortality. Asymmetric septal hypertrophy and impairment of LV
      outflow can occur in these patients and may contribute to adverse outcomes. More
      insight into the prevalence, extent, geometry, and promoting factors of LV
      hypertrophy is important. METHODS: An unselected group of 62 patients (31 women),
      aged 55 +/- 14 years, on maintenance hemodialysis was investigated by Doppler
      echocardiography. Eight patients with valvular heart disease were excluded from
      further analysis. We assessed prevalence of LV hypertrophy and asymmetric septal
      hypertrophy, as well as parameters of LV geometry and LV filling and outflow
      dynamics. RESULTS: Prevalence of LV hypertrophy was 65%. Patients were analyzed
      according to LV mass and geometry. Mean LV mass index was normal (105 +/- 17
      g/m2) in Group 1 without LV hypertrophy (n = 19); it was markedly elevated in
      Group 2 (symmetric hypertrophy, n = 22) and Group 3 (asymmetric hypertrophy with
      systolic anterior movement of mitral valve, n = 7), and highest (191 +/- 54 g/m2)
      in Group 4 (asymmetric hypertrophy without systolic anterior movement of mitral
      valve, n = 6, p < 0.001). Age, body mass index, and duration of hypertension were
      associated with LV hypertrophy and asymmetric septal hypertrophy (p = 0.01).
      Group 3 with systolic anterior motion of mitral valve had the smallest end
      diastolic LV diameters (p = 0.02); increased heart rates, and increased ejection
      velocities in the LV outflow tract (p = 0.03, and p = 0.005, respectively, vs.
      Groups 1, 2, and 4) which pointed to an impairment of LV outflow. CONCLUSIONS:
      Symmetric LV hypertrophy and asymmetric septal hypertrophy are frequent in
      patients on maintenance hemodialysis. Predictors for LV hypertrophy were age and
      body mass index, and, particularly for asymmetric septal hypertrophy, age and
      hypertension duration. Volume withdrawal during hemodialysis may lead to
      symptomatic hypotension due to dynamic obstruction in some patients with severe
      asymmetric septal hypertrophy.

PMID- 9755386
TI  - Incidence and prognostic value of electrocardiographic abnormalities after heart
      transplantation.
AB  - BACKGROUND: The improvement of surgical techniques and the use of
      immunosuppressive drugs within the past 15 years has made heart transplantation
      an increasingly performed procedure and an accepted treatment for end-stage
      cardiac failure. HYPOTHESIS: The aim of this study was to describe the changes of
      the 12-lead electrocardiogram (ECG) after heart transplantation and to determine
      their prognostic value on complications such as rejection or graft coronary
      artery disease during follow-up. METHODS: The ECGs of 62 consecutive patients
      were analyzed for 5 years at follow-up periods of 1, 2, 3, 6 months and yearly
      after transplantation. RESULTS: The most prevalent abnormality was the presence
      of complete or incomplete right bundle-branch block (RBBB). New RBBB appeared in
      69% (43/62) of the patients, mainly during the first month (21/43). There was no
      left bundle-branch block. We detected nine episodes of supraventricular
      arrhythmias: one atrial fibrillation, six atrial flutter, one junctional
      tachycardia, one orthodromic tachycardia on a Wolff-Parkinson-White syndrome; all
      appearing during the first 3 months. Three of the six episodes of atrial flutter
      occurred during an episode of acute rejection. There was no relation between RBBB
      and the gender and age of recipients and donors, nor with the graft ischemic time
      and the pretransplantation hemodynamic values. Right bundle-branch block was not
      associated with acute rejection nor with graft coronary artery disease.
      CONCLUSION: The ECG abnormalities after heart transplantation have no predictive
      value on the long-term evolution. Right bundle-branch block is very frequent and
      is not associated with adverse prognosis.

PMID- 9755387
TI  - Images in cardiology. Acquired interventricular septal defect.

PMID- 9755388
TI  - Acute myocardial infarction in two adolescent males.
AB  - Acute myocardial infarction in previously healthy children is rare in the absence
      of congenital anomalies. We describe two cases of acute anterior myocardial
      infarction in adolescent males with no congenital heart disease, without prior
      history of or risk factors for coronary heart disease, and with no history of
      drug abuse. These cases illustrate that myocardial infarction in the absence of
      systemic illness or coronary anomalies can occur in an adolescent population.

PMID- 9755389
TI  - Constrictive pericarditis after coronary artery bypass surgery as a cause of
      unexplained dyspnea: a report of five cases.
AB  - Constrictive pericarditis after coronary artery bypass grafting (CABG) is rare
      and can present as unexplained dyspnea. We report five consecutive cases of post
      CABG constrictive pericarditis seen within a period of 17 months at our
      institution. All patients presented with heart failure of unknown etiology within
      a period of 8-84 months after surgery. During the initial post-CABG period, two
      patients had developed postcardiotomy syndrome that was successfully treated with
      steroids. They were all assessed noninvasively and invasively. In all patients,
      the diagnosis of constriction was initially suspected clinically (symptoms, high
      jugular venous pressure with deep "X" and "Y" descents, pericardial knock).
      Echocardiography showed transmitral flow typical of constriction in all patients
      and hepatic venous flow in two. Two patients showed rapid left ventricular
      relaxation. In all patients, hemodynamic assessment showed diastolic equalization
      of pressures in all chambers, "W" shape waveform in right atrial pressure, and
      "dip and plateau" configuration in right and left ventricular pressure waveforms.
      Diagnosis was confirmed surgically in four patients who were subjected to
      pericardiectomy-pericardial stripping (three survived, one died). One patient
      refused surgery. We conclude that constrictive pericarditis, although rare,
      should be suspected in every case of unexplained dyspnea post CABG. It can appear
      early or late after surgery, and clinical examination plays an important role in
      its early recognition. It requires a full noninvasive and invasive assessment in
      case of clinical suspicion.

PMID- 9755390
TI  - Obituary: Herbert N. Hultgren.

PMID- 9755391
TI  - Atheromatous plaque reflects serum total cholesterol levels: a comparative
      morphologic study of endarterectomy coronary atherosclerotic plaques removed from
      patients from the southern part of India and Caucasians from Ottawa, Canada.

PMID- 9755392
TI  - Correlation of 3D MRI and clinical findings in the patients with sensorineural
      hearing loss and/or vertigo.
AB  - The aim of the study was to correlate clinical and magnetic resonance imaging
      (MRI) (3D CISS and MP-RANGE) findings in patients with sensorineural hearing loss
      (SNHL) and/or vertigo. We found a high correlation of MRI and symptoms (17 out of
      18 patients, 13 out of 13, respectively) concerning detectability of tumors and
      acute labyrinthitis. In the case of labyrinthine fibrosis, the correlation
      between clinical and MRI findings was lower. In conclusion, high-resolution MRI
      is very suitable in patients with SNHL or vertigo caused by tumors or acute
      labyrinthitis.

PMID- 9755393
TI  - Neurosarcoidosis presenting as a large suprasellar mass. Magnetic resonance
      imaging findings.
AB  - We present unusual magnetic resonance imaging (MRI) findings in a case of
      neurosarcoidosis. MRI revealed a large solitary suprasellar mass which resembled
      a neoplasm. The lesion was isointense and hyperintense on T1-weighted images,
      hypointense on T2-weighted images, and intensely homogeneously enhancing. Biopsy
      revealed a polymorphous inflammatory lesion with giant cells, which extended from
      the hypothalamus, consistent with neurosarcoidosis. The diagnosis of
      neurosarcoidosis should be considered in patients presenting with large midline
      tumor-like suprasellar mass lesions.

PMID- 9755394
TI  - Pituitary gland. Variable signal intensities on MRI. A pictorial essay.
AB  - The anterior pituitary gland may exhibit high signal on T1-weighted (T1w) images
      and/or low signal on T2-weighted (T2w) images in several normal and pathological
      states. High T1w signal may be seen in normal fetuses, neonates, and in pregnant
      and postpartum women. It may also occur in Rathke's cleft cyst,
      craniopharyngioma, subacute hemorrhage, manganese deposition, melanoma, dermoid,
      and lipoma. Low T2w signal may be seen in hemorrhage, calcification, cystic
      lesion, hemochromatosis, melanoma, and vascular lesions. These are described and
      illustrated.

PMID- 9755395
TI  - Small cortical infarcts mimicking metastatic tumors.
AB  - Small cortical enhancing lesions mimicking metastases were demonstrated on
      contrast imaging in three patients without specific neurologic deficits
      corresponding to the lesions. One patient had a long carcinoma. However, all had
      cardiac arrhythmias known as major sources of cerebral emboli. Two had early
      cerebral infarcts and ischemic heart diseases. The lesions disappeared
      spontaneously on follow-up studies. They were subsequently presumed to be small
      infarcts. Clinical information and follow-up examinations are important to
      differentiate these small cortical lesions from metastases.

PMID- 9755396
TI  - High-resolution CT pulmonary findings in adults with Gaucher's disease.
AB  - The purpose of this study was to illustrate high-resolution computed tomography
      (HRCT) findings in symptomatic adult Gaucher's disease patients. Five adult
      patients with Gaucher's disease experienced dyspnea. These patient were first
      evaluated by chest X-ray (CXR) followed by HRCT. The chest X-ray on one patient
      demonstrated a calcified granuloma. Two patients had interstitial disease only
      seen on HRCT, and two patients had a combination of interstitial and alveolar
      disease giving a mosaic pattern better illustrated on HRCT. HRCT can be used
      following CXR to evaluate lung pathology in symptomatic adult Gaucher's disease
      patients.

PMID- 9755397
TI  - Breast carcinoma metastatic to the esophagus. CT findings with pathologic
      correlation.
AB  - The common sites of metastasis from breast carcinoma include local and distant
      lymph nodes, lung parenchyma, bone, liver and brain. While less common,
      gastrointestinal carcinoma, involving everything from the tip of the tongue to
      the rectum, secondary to metastatic breast carcinoma have been reported. Many of
      these lesions occur years after treatment of the primary breast cancer and they
      can be confused with a second primary. We present a case of breast cancer
      metastatic to the esophagus which produced symptoms of progressive dysphagia in a
      women thirteen years after mastectomy and radiation therapy for breast cancer.

PMID- 9755398
TI  - Cystic fibrosis: spectrum of thoracic and abdominal CT findings in the adult
      patient.
AB  - Cystic fibrosis (CF) is an autosomal recessive disorder that is characterized by
      an abnormality of exocrine gland function. Adult patients represent a rapidly
      growing percentage of the CF population. Pulmonary changes are seen in nearly
      every case and are the most serious complication of CF. In advanced lung disease,
      bronchiectasis, emphysematous bullae, and subpleural blebs can frequently
      develop. Although pulmonary disease is the most common cause of death and
      morbidity among CF patients, there also can be involvement of other groups,
      particularly in adults, which show characteristic signs on CT and spiral CT.
      Pancreatic abnormalities are present in 85-90% of CF patients. The degree of
      pancreatic involvement varies, ranging form accumulations of mucus in the small
      ducts to totally plugged ducts, which can cause atrophy of the exocrine glands
      and progressive fibrosis. Pancreatic dysfunction on CT is demonstrated as fatty
      replacement and fibrosis of the pancreas. However, there may be scattered foci of
      pancreatic calcifications that can be detectable on plain radiographs.
      Hepatobiliary involvement follows the same pattern as pancreatic abnormalities.
      Bile canaliculi are plugged by mucinous material and when this plugging is of
      long duration, biliary cirrhosis with diffuse hepatic nodularity may develop.
      Such severe hepatic involvement is see in only about 2-5% of patients, although
      minor hepatic alterations, such as diffuse fatty changes, are fairly common.
      Hepatobiliary involvement is characterized by hepatic nodularity, compatible with
      cirrhosis, splenomegaly, and ascites. Complete obstruction of the ileum by
      meconium occurs in approximately 10% of newborns with CF. Intestinal findings on
      CT include obstruction, although this is more common in children. These CT signs
      should be evaluated carefully in adult patients since they may be suggestive of
      CF. Computed tomography offers unique information about organ involvement (other
      than pulmonary) that can alter diagnosis and patient management.

PMID- 9755399
TI  - Endoscopic ultrasonography for preoperative locoregional staging and assessment
      of resectability in gastric cancer.
AB  - We performed a prospective study from November 1989 to December 1996 to assess
      the accuracy of endoscopic ultrasonography (EUS) in the locoregional staging and
      resectability of patients with gastric carcinoma. One hundred and nineteen
      patients with gastric cancer who received preoperative assessment by EUS
      underwent subsequent surgery. The endosonographic tumor-node-metastasis (TNM)
      classification was used for comparison with the histopathologic findings of the
      resected specimens. The ability of EUS to accurately predict the T stage (depth
      of tumor invasion) and N stage (involvement of lymph node) was 70% and 65%,
      respectively. EUS displayed a tendency to overestimate T stage and underestimate
      N state. The differentiation of early gastric cancer from advanced gastric cancer
      showed a concordance rate of 89% and underestimation rate of 8% and
      underestimation rate of 3%. The accuracy of EUS in predicting the stage T1 to T3,
      which correspond to D0 resectability (no macroscopic or microscopic tumor
      remains), was 91%. In conclusion, these results revealed EUS as a valuable tool
      for evaluating the local staging and resectability of gastric cancer. We suggest
      that EUS should be introduced in the preoperative assessment of patients with
      gastric cancer.

PMID- 9755400
TI  - Portal venous aneurysm demonstrated by magnetic resonance imaging.
AB  - Portal venous aneurysm is an unusual vascular abnormality. We present this entity
      with magnetic resonance imaging (MRI) findings showing characteristic flow
      abnormality in two patients. Ultrasound examination revealed hyperechoic
      lobulated masses in the portal vein and the duplex Doppler study confirmed the
      venous flow patterns of low resistance within the lesion. The literature
      regarding this entity and the potential role of MRI are briefly discussed.

PMID- 9755401
TI  - Thin-section CT follow-up of metastatic ovarian carcinoma correlation with levels
      of CA-125 marker and clinical history.
AB  - Second-look laparotomy and CA-125 are the gold standard in follow-up of ovarian
      carcinoma. Since no definite role seems established for cross-sectional imaging
      in assessment of recurrence we employed thin-section computed tomography (CT),
      correlated with CA-125 levels and detailed knowledge of the clinical history as a
      follow-up protocol One hundred seventy-seven patients with ovarian carcinoma were
      selected because of: (a) pathologically proven remission after first-line
      chemotherapy, (b) follow-up by means of thin-section CT every 6 months for the
      fist 3 years and every 10 months subsequently, (c) monitoring CA-125 serum levels
      every 3 months for the first 3 years and every 6 months subsequently; (d)
      pathologic confirmation or clinical and laboratory follow-up after 12 months or
      longer for the CT findings. Fifty percent of the patients showed recurrence of
      disease. Our protocol yielded 93.2% true positive, dubious findings in 5.6% 1.0%
      false negatives, 97.7% true negative, and 2.3% false positive. With a tailored
      technique, CT was particularly sensitive in early diagnosis of peritoneal
      seeding, even in the absence of ascites or increases in the levels of CA-125.
      Repeated administration of contrast medium, water enemas, and repeated scanning
      of suspicious volumes with differing scanning parameters were the factors managed
      by the radiologist. We conclude that thin-section CT, correlated with CA-125
      levels and careful review of the clinical history could represent a valid
      alternative to repeated explorative laparotomies in the follow-up of ovarian
      carcinomas.

PMID- 9755402
TI  - Prevalence and patterns of tendon calcification in patients with
      chondrocalcinosis of the knee: radiologic study of 156 patients.
AB  - The presence or absence of tendon calcification was studied at six anatomic
      sites: Achilles, gastrocnemius, quadriceps, triceps (elbow), triceps long head
      (shoulder), and rotator cuff. The morphology of the calcifications was
      categorized in 156 patients with chondrocalcinosis in the knee. Achilles tendon,
      gastrocnemius, and quadriceps tendon calcifications were most common, ranging
      from 21%-25% of our patient population was thin linear bands. Triceps
      calcification at the elbow, rotator cuff calcifications, and long head of triceps
      tendon calcification were less common.

PMID- 9755403
TI  - Auditing surgical outcome: ten years with the Swedish Vascular Registry-
      Swedvasc. The Steering Committee of Swedvasc.

PMID- 9755404
TI  - Vascular registries as a method for research and quality development.

PMID- 9755405
TI  - Auditing surgical outcome. The Swedish experience.

PMID- 9755406
TI  - Examples of studies performed within Swedvasc.

PMID- 9755407
TI  - Intestinal ischaemia after aortoiliac surgery--a case-control study within the
      Swedvasc Registry.

PMID- 9755409
TI  - Outcome and influence of age after infrainguinal revascularization in critical
      limb ischemia.

PMID- 9755408
TI  - Low-molecular weight heparin versus dextran in the prevention of early occlusion
      following arterial bypass surgery distal to the groin.

PMID- 9755412
TI  - Follicle stimulating hormone and its receptor: future perspectives.
AB  - In this report, we review our present effort in the field of molecular
      reproductive endocrinology: to identify a small molecular weight follicle
      stimulating hormone (FSH) agonistic molecule. To achieve this goal we require a
      number of molecular tools. We have cloned and expressed the human gonadotrophin,
      FSH and the human FSH receptor and developed a reliable high throughput assay. We
      have also proposed a model to explain FSH receptor activation and from that
      model, begun to create small molecules predicted to induce FSH signal
      transduction without binding to the extracellular domain of the membrane protein.
      In this report, we summarize our efforts to date and discuss our future research
      efforts in this area.

PMID- 9755411
TI  - New approaches to ovarian stimulation.
AB  - Suppression of endogenous hormone production by gonadotrophin-releasing hormone
      (GnRH) agonists followed by controlled ovarian hyperstimulation (COH) with human
      gonadotrophins, especially the so-called 'long protocol' has developed from
      second-line into first-line therapy. Due to this attitude premature luteinization
      can be safely avoided, enhancing therapeutic efficacy. Recombinant preparations
      of human follicle stimulating hormone (FSH) have been proven to be effective
      within COH according to the long protocol. The high purity of these compounds may
      have clinical advantages. GnRH antagonists could be successfully introduced in
      COH protocols. Also, daily injections in the midcycle phase according to the
      'Lubeck protocol', as single or only dual administrations around day 9 seem to
      abolish any premature LH rises. Due to their different pharmacological mode of
      action, based on a classic competitive receptor blockage GnRH antagonists avoid
      any flare-up period and allow ovarian stimulation to start within the spontaneous
      cycle. Pregnancy rates are comparable to those after long protocol stimulation.
      Combination of softer stimulation regimes like clomiphene citrate and low dose
      HMG with midcycle administration of GnRH antagonists may be the way to a cheap,
      safe and efficient ovarian stimulation. It seems to be high time for modest forms
      of ovarian stimulation, lowering burden and risk for our patients.

PMID- 9755413
TI  - Developments in human recombinant follicle stimulating hormone technology: are we
      going in the right direction?
AB  - Recent developments in recombinant DNA technology have enabled the large scale
      production of human recombinant follicle stimulating hormone (rFSH); and this
      compound has recently been introduced to the market. Understanding of the
      structure-function relationship of FSH isohormones is crucial in understanding
      discussions on the standardization procedures of gonadotrophin preparations,
      potential differences in clinical efficacy of the various gonadotrophin
      preparations and in comprehending future developments (long-acting and short
      acting forms, and rFSH preparations with altered isohormone profiles).
      Differences between immunoreactive and bioactive serum FSH concentrations have
      been observed following the administration of rFSH. Accordingly, the isohormone
      distribution of rFSH is similar to, but not identical with, natural human FSH.
      Issues relevant to daily practice discussed in this review include: the total
      absence of urinary contaminants allowing for the safe s.c. administration of the
      compound. Production is independent from urine, and the capacity can be adjusted
      according to clinical needs. The relationship between serum oestradiol
      concentrations and number and size of follicles observed by ultrasound may change
      when rFSH is combined with gonadotrophin-releasing hormone (GnRH) agonist, due to
      low serum lueinizing hormone (LH) concentrations. In the case of endogenous serum
      LH concentrations within the normal range, exogenous administration of LH is
      redundant. In the near future, rFSH preparations with altered bioactivity will be
      available.

PMID- 9755415
TI  - Immature oocyte retrieval combined with in-vitro oocyte maturation.
AB  - Immature oocyte retrieval combined with in-vitro oocyte maturation has a
      considerable potential to increase knowledge on the microenvironment and nuclear
      and cytoplasmic maturation, and may be an alternative or even replacement for
      routine in-vitro fertilization as practised today. Understanding the critical
      steps to accomplish this task demands ongoing research to produce a comparable
      microenvironment to that of the developing follicle. This will allow cytoplasmic
      maturation to occur, and clarify knowledge on the selection of the dominant
      follicle, and utilize novel aspects fertilization and embryo culture in vitro. A
      second aspect of the produce concerns its clinical aspects. These include a
      better understanding of the number of antral follicles that can be retrieved
      transvaginally and the nature of the endometrial window and its advancement in
      order to provide a window of opportunity for implantation to occur.

PMID- 9755414
TI  - Oocyte maturation.
AB  - Primary oocytes recovered from small and growing follicles of > or = 3 mm in the
      ovaries of untreated women, can be matured in vitro, will fertilize and develop
      in vitro, and when transferred to the patient, develop to term. However, the
      implantation rate of cleaved embryos has been disappointingly low and when
      embryos are allowed to develop beyond the 4-cell in vitro, retardation of
      development and blockage is frequently observed, with relatively few embryos
      developing to blastocysts. We have devised new culture systems for human embryos
      to enable high rates of development of in-vivo matured oocytes to blastocysts
      within 5-6 days of culture, and high implantation rates of these blastocysts when
      they are transferred to the patients' uterus. These culture systems are now being
      used for in-vitro matured oocytes. In order to determine whether embryo
      developmental competence could be improved, a number of factors were examined.
      Treatment of patients with pure follicle stimulating hormone (FSH) early in the
      follicular phase, or treatment with oestrogen prior to oocyte recovery, had no
      apparent effect on any parameters of oocyte developmental competence. There was
      no indication that a medium made specifically for human oocyte maturation
      improved oocyte developmental competence. Nuclear and cytoplasmic changes in
      oocytes matured in vitro appear to be similar to that in vivo, although some lack
      of synchronization in completing maturation is evident. It is possible that
      follicles of < 10 mm diameter in the human contain developmentally-incompetent
      oocytes. However, the development to term and birth of normal babies from
      germinal vesicle stage oocytes recovered from small follicles and matured in
      vitro, suggests that further research will identify the factors necessary to
      improve embryo developmental competence. The application of immature oocyte
      collection (IOC) and in vitro maturation (IVM) as an alternative to ovulation
      stimulation with high doses of gonadotrophins for in-vitro fertilization (IVF),
      remains a priority for research in human medicine.

PMID- 9755416
TI  - Genetic contribution to male infertility.
AB  - Worldwide, of couples trying for a child, 2-7% fail to conceive. Extensive
      screening programmes of men attending infertility clinics show that chromosomal
      and gene disorders make a significant contribution to spermatogenic impairment.
      It appears that an orderly genome is essential for normal germ cell development,
      since numerical and structural chromosome abnormalities are found in association
      with germ cell breakdown. The most recent research indicates that genes on the Y
      chromosome and autosomes are involved in spermatogenic control.

PMID- 9755417
TI  - Spermatids as gametes: indications and limitations.
AB  - The feasibility of achieving viable embryos, developing to term after transfer
      into the uterus, by fertilizing oocytes with spermatids has been demonstrated
      both in animal studies and in preliminary human clinical trials. Here we review
      the current clinical indications of spermatid conception and discuss the
      predictable success rates associated with each of these indications. Potential
      health hazards relating to the use of spermatids for conception are updated
      taking into account the risk of abnormal or incomplete epigenetic modifications
      of newly discovered human imprinted genes. We also add new experimental data
      showing the occurrence of spermatids in patients lacking spermatozoa and
      demonstrating that round spermatids recovered from patients with complete
      spermiogenesis failure (no elongated spermatids or spermatozoa ever detected in
      the patient's history) are often deficient in the factor(s) responsible for
      oocyte activation. The possible consequences of this deficiency for the
      occurrence of abnormal fertilization patterns and for the impairment of further
      preimplantation and post-implantation development are discussed. It is concluded
      that the development of diagnostic tests to assess the intrinsic quality of
      spermatids, with regard to their ability to act as gametes, is urgently needed as
      part of pre-treatment diagnosis before infertile couples are included in a
      spermatid conception programme. Centres wishing to use spermatids in human
      assisted reproduction should also be prepared to offer adequate diagnostic
      methods to control genomic imprinting abnormalities in the progeny.

PMID- 9755418
TI  - Clinical application of new micromanipulative technologies to treat the male.
AB  - Traditional treatments of the male have produced no improvement in sperm
      parameters. Since the rate of normal fertilization rate is significantly lower in
      these cases after classic in-vitro fertilization (IVF), intracytoplasmic sperm
      injection (ICSI) has become the preferred method of treatment. It has been
      successfully applied in cases of extreme oligoasthenoteratozoospermia, and
      obstructive and non-obstructive azoospermia. Cryopreservation of testicular
      tissue will replace the repeated use of fresh testicular tissue. Full information
      has to be provided to patients about the frequency (approximately 3%) of sex
      chromosome and autosomal aberrations in men with extreme
      oligoasthenoteratospermia. The need for screening for Yq deletions is still under
      study, and any therapeutic consequences for the newborn child will have to be
      analysed. The incidence of major malformations in newborn children is
      approximately 2.5%, i.e. comparable with that of the general population.
      Screening for de-novo sex chromosome aberrations may be particularly useful for
      men with sperm counts of < 5 x 10(6) and those with non-obstructive azoospermia.

PMID- 9755419
TI  - New approaches to achieving human fertilization: a resume.

PMID- 9755420
TI  - Culture and quality control of embryos.
AB  - Improvement of embryo quality during in-vitro culture can be achieved by
      understanding and controlling the requirements of gametes and embryos. The most
      obvious route is to alter culture media, but standardization could be influenced
      by diverse environmental factors. Abnormal embryos from patients with multiple
      failures probably do not benefit from standardization and require specialized
      therapy, that is if their physiology is not already irreversibly jeopardized
      during gametogenesis. This paper describes the adverse environmental factors
      present in laboratory air and released by common products used by laboratories.
      Assays and results of the air determinations in several laboratories are
      reported, as well as potential counter measures. The possibility of altering the
      immediate environment of the nucleus of the egg by ooplasmic transplantation is
      also considered, and the first attempts resulting in two ongoing pregnancies are
      reported.

PMID- 9755421
TI  - Culture of viable human blastocysts in defined sequential serum-free media.
AB  - In human in-vitro fertilization (IVF), embryos are routinely transferred to the
      uterus on either day 2 or day 3 of development, resulting in a 10-15%
      implantation rate. However, in other mammalian species, the transfer of cleavage
      stage embryos, which normally reside in the oviduct, to the uterus results in a
      significantly lower implantation rate compared with blastocysts. It is therefore
      proposed that, in order to increase implantation rates in human IVF, one has to
      move to extended culture and transfer at the blastocyst stage. The transfer of
      blastocysts will not only help synchronize the embryo with the female tract but
      will facilitate the identification of those embryos with little or no
      developmental potential. In order to culture viable blastocysts it is important
      to use more than one culture medium to cater for the changing requirements of the
      preimplantation embryo as it develops and differentiates. If sequential culture
      media are not used, one can obtain blastocysts but their resultant viability is
      low. The use of sequential serum-free media in human IVF has resulted in > 50% of
      embryos becoming blastocysts with an implantation rate of approximately 50%.
      Further advances in human embryo culture should come from the replacement of
      protein with the glycosaminoglycan hyaluronate, which is more suitable than
      albumin in supporting implantation in the mouse, and which will eliminate
      biological variation and possible contamination from blood products. With the
      routine culture of human blastocysts will come the introduction of non-invasive
      tests of embryo viability, capable of identifying those blastocysts most likely
      to develop from a given cohort. As the implantation rate of blastocysts is higher
      than that of the cleavage stage embryo, fewer embryos will be required for
      transfer in order to establish a successful pregnancy, thereby reducing the
      number of multiple gestations and increasing the overall efficiency of human IVF.

PMID- 9755422
TI  - Cryopreservation in human assisted reproduction is now routine for embryos but
      remains a research procedure for oocytes.
AB  - Human embryo cryopreservation represents an indispensable extension of in-vitro
      fertilization (IVF) programmes as long as they are based upon the recovery of a
      large number of oocytes. The most widely used procedures include the
      cryopreservation of human zygotes or embryos in early cleavage, using 1,2
      propanediol and sucrose as cryoprotectants. Our results over a 10 year period
      (1986-1995) on 5032 thawed cycles involving 14 222 stored embryos make it
      possible to appraise the results and the contribution of embryo freezing to
      assisted reproduction. Embryos survived the freeze-thaw process in 73% of cases
      leading to 4590 transfers of 2.2 embryos (91% of thawed cycles). The clinical
      pregnancy rate per transfer was 16%, the live birth rate 12%, and the rate of
      babies born alive per transferred embryo was 6%. Embryo freezing monitored 10
      years later produced an average of 8% of additional births. By then, 86% of
      stored embryos had been thawed for transfer to patients. Destruction or donation
      were required for only 8% of all frozen embryos and there was no news from the
      parental couple in relation to almost 6% of embryos. The fate of the vast
      majority of embryos was decided during the first 5 years of storage. Blastocyst
      cryopreservation is making new strides, thanks to co-culture systems and embryo
      selection. Micromanipulation procedures seem to have little impact on the outcome
      of embryo freezing. Human oocyte freezing is again clinically applied. Indeed,
      much of the concern about injuries to the oocyte structures through the freeze
      thaw process do not seem to be justified, and the problems with frozen-thawed
      oocyte fertilization has been overcome using intracytoplasmic sperm injection
      (ICSI). As long as oocyte in-vitro maturation is not well controlled, better
      results will probably be obtained with mature oocyte cryopreservation. Emerging
      methods include the freezing of immature oocytes, follicles and ovarian tissue.

PMID- 9755423
TI  - Genetic regulation of egg and embryo survival.
AB  - In both mice and humans, 15-50% of embryos die during the preimplantation period
      from mechanisms that are largely unknown. Two major criteria predict
      preimplantation embryo quality, the rate of development and the degree of
      fragmentation. We review evidence that both of these criteria have a genetic
      basis. Rate of development and subsequent embryo survival are controlled by a
      gene, Ped, we discovered in the mouse. Although progress is being made in the
      search for the human homologue of the mouse Ped gene, it has not yet been
      identified. Fragmentation, observed in both mouse and human embryos, is probably
      the result of apoptosis. We analysed transcription of two genes that regulate
      apoptosis, bcl-2 and bax, and found that both are transcribed in mouse and human
      preimplantation embryos. Overall, the literature reviewed and new data presented
      in this paper support the concept that there is a genetic basis for
      preimplantation egg and embryo survival.

PMID- 9755424
TI  - How to avoid multiple pregnancies in assisted reproduction.
AB  - The international rates of triplet or higher order pregnancies after assisted
      reproduction are 7.3% at conception, 6.5% before reduction and 3.85% at birth.
      The obstetric and neonatal outcomes for twins and triplets show that reducing the
      proportion of multiple pregnancies should be a goal for centres undertaking in
      vitro fertilization (IVF) and embryo transfer.

PMID- 9755425
TI  - Molecular interactions between embryo and uterus in the adhesion phase of human
      implantation.
AB  - Molecular interactions at the embryo-maternal interface at the time of
      implantation is an exciting field demanding a wide effort in order to understand
      the crucial process of embryonic implantation. The objective of the present work
      is to demonstrate the existence of a specific communication pathway (at the
      molecular level) between embryo and endometrium in the adhesion phase of human
      embryonic implantation. This pathway of molecular interactions is apparently
      initiated by the endometrium in the presence of an implanting blastocyst. It is
      mediated through the embryonic interleukin 0(IL)-1-alpha + IL-1-beta, and the
      target is the endometrial epithelial beta-3 integrin subunit. If the relevance of
      beta-3 is accepted as a marker of uterine receptively, these observations may
      imply that the normal hormonally-regulated human endometrium is the trigger of
      molecular events preparing the blastocyst to efficiently communicate and regulate
      endometrial adhesion molecules in order to implant.

PMID- 9755426
TI  - The role of leukemia inhibitory factor and interleukin-6 in human reproduction.
AB  - There is now strong evidence that many of the actions of steroids in controlling
      reproduction are mediated by locally acting factors such as growth factors and
      cytokines. These have been shown to act both in an autocrine and paracrine manner
      to regulate preimplantation embryo development and migration which is necessary
      for placental development. The creation of mouse strains lacking genes for
      receptors or growth factors has proved important in defining which of these are
      essential in reproduction in this species and those that play a lesser role.
      Using this approach, a lack of leukemia inhibitory factor (LIF) in the murine
      endometrium has been shown to result in failed implantation. Evidence from
      infertile women supports the notion that abnormal expression of LIF, or the
      related cytokine interleukin-6 (IL-6) in the endometrium may underlie some forms
      of human infertility. This offers the opportunity for therapeutic intervention,
      if levels of these cytokines can be altered in a specific and controlled way. The
      recently described method of delivery of genes to the uterine epithelium provides
      a powerful new approach by which this could be achieved. The ability to regulate
      the function of specific genes in the endometrium by direct gene transfer raises
      the prospect of novel opportunities for therapeutic intervention.

PMID- 9755427
TI  - Endometrial integrins and the establishment of uterine receptivity.
AB  - Our understanding of the factors responsible for the initial interaction between
      maternal and embryonic epithelium leading to successful implantation remains
      incomplete. Temporal and spatial expression of specific endometrial peptides may
      contribute to the establishment of a period of uterine receptivity, whereby the
      endometrium becomes hospitable to the implanting blastocyst. The failure to
      establish receptivity may account for a significant number of cases of
      infertility in the female, especially affecting women with luteal phase
      deficiency, endometriosis, hydrosalpinges, recurrent pregnancy loss and
      unexplained infertility. Integrins are a family of cell adhesion molecules that
      have now been largely accepted as markers of uterine receptivity. Their pattern
      of expression during the menstrual cycle suggests that integrins may also provide
      a means to study the factors that regulate the establishment of uterine
      receptivity in general. The vitronectin receptor is an alpha-v-beta-3 integrin
      that appears during the opening of the putative window of implantation. Its
      expression appears to be associated with the down-regulation of epithelial
      oestrogen and progesterone receptors (PR). We postulate that the selective loss
      of PR on endometrial epithelium is critical to the establishment of uterine
      receptivity and allows the emergence of paracrine influence by underlying stroma
      through specific growth factors. Disruption of the normal pattern of integrins
      found in certain infertility states may also reflect a shift in the paracrine
      milieu, possibly due to the influence of inflammatory cytokines associated with
      endometriosis or tubal disease. Understanding what regulates and dysregulates
      endometrial integrins may lead to better treatment and diagnostic strategies for
      infertility patients as well as novel approaches to contraception.

PMID- 9755428
TI  - Glycodelins: role in regulation of reproduction, potential for contraceptive
      development and diagnosis of male infertility.
AB  - Glycodelins are glycoproteins synthesized in various glands, with sequence
      homology to beta-lactoglobulins, and named according to their unique
      oligosaccharide structures. We purified, cloned and sequenced endometrium- and
      seminal plasma-derived glycodelins (GdA and GdS respectively) and found that they
      are involved in various types of cell-cell communications. These include
      interactions between the spermatozoon and the egg, and between immune cells and
      their targets. Endometrial GdA inhibits sperm-egg binding, whereas the
      differently glycosylated GdS in seminal plasma does not. These observation are of
      interest for reproductive physiology, detection of causes of infertility, and
      they also may have potential for contraceptive development.

PMID- 9755429
TI  - New concepts in embryonic growth and implantation.

PMID- 9755432
TI  - [In vitro antibacterial activity of vancomycin in combination with panipenem
      against carbapenem-resistant MRSA].
AB  - The synergistic relationship between vancomycin (VCM) and carbapenem (CRB) has
      been reported in antibacterial activity against CRB-resistant strains of MRSA.
      The purpose of this study is to investigate the antibacterial activity against
      CRB-resistant MRSA using VCM, panipenem (PAPM), and a combination of both. 8
      strains of CRB-resistant MRSA were used to examine the effects of these
      antibiotics by the broth microdiluton technique. The effect of pH (pH 6, 7, 8) on
      MIC of VCM alone was not observed in 7 out of 8 strains; MICs were between 1.0
      2.0 micrograms/ml. PAPM alone, however, showed an enhancing tendency in alkaline
      condition in 6 out of 8 strains. There was no influence of pH on MICs in the
      combination use of VCM and PAPM, showing additive effect in 1 strain and
      synergistic in 6 strains. Killing-curves against PAPM-resistant MRSA were
      examined under the following drug combinations; 1/4 MIC of VCM (0.5
      micrograms/ml) plus 1/4 MIC of PAPM (16 micrograms/ml), and 1/4 MIC of VCM plus
      1/8 MIC of PAPM (8 micrograms/ml). The former drug combination showed synersistic
      effect; decrease from 1.05 x 10(5) to 6.45 x 10(4) CFU/ml after 6 hours'
      incubation and to less than 10 CFU/ml after 24 hours. The latter drug combination
      showed synergistic activity (2.68 x 10(2) CFU/ml) after 24 hours' incubation, but
      lost antibacterial activity after 48 hours. In conclusion, PAPM in combination
      with VCM showed synergistic effects on CRB-resistant MRSA. This combination
      therapy should be evaluated for the treatment of MRSA infection in patients with
      renal dysfunction.

PMID- 9755430
TI  - [Susceptibilities of bacteria isolated from patients with lower respiratory
      infectious diseases to antibiotics (1996)].
AB  - The bacteria isolated from the patients with lower respiratory tract infections
      were collected by institutions located throughout Japan, since 1981. Ikemoto et
      al. have been investigating susceptibilities of these isolates to various
      antibacterial agents and antibiotics, and characteristics of the patients and
      isolates from them each year. Results obtained from these investigations are
      discussed. In 16 institutions around the entire Japan, 557 strains of presumably
      etiological bacteria were isolated mainly from the sputa of 449 patients with
      lower respiratory tract infections during the period from October 1996 to
      September 1997. MICs of various antibacterial agents and antibiotics were
      determined against 98 strains of Staphylococcus aureus, 93 strains of
      Streptococcus pneumoniae, 84 strains of Haemophilus influenzae, 84 strains of
      Pseudomonas aeruginosa (non-mucoid strains), 17 strains of Pseudomonas aeruginosa
      (mucoid strains), 31 strains of Moraxella subgenus Branhamella catarrhalis, 21
      strains of Klebsiella pneumoniae etc., and the drug susceptibilities of these
      strains were assessed except for those strains that died during transportation.
      1) S. aureus S. aureus strains for which MICs of oxacillin (MPIPC) were higher
      than 4 micrograms/ml (methicillin-resistant S. aureus) accounted for 67.3%. The
      frequency of the drug resistant bacteria increased comparing to the previous
      year's 52.7%. Arbekacin (ABK) and vancomycin (VCM) showed the highest activities
      against both S. aureus and MRSA with MIC80s of 1 microgram/ml. 2) S. pneumoniae
      Imipenem (IPM) and panipenem (PAPM) of carbapenems showed the most potent
      activities with MIC80s of 0.063 microgram/ml. Faropenem (FRPM) showed the next
      potent activity with MIC80 of 0.125 microgram/ml. The other drugs except
      erythromycin (EM), clindamycin (CLDM) and tetracycline (TC) were active against
      S. pneumoniae tested with MIC80s of 8 micrograms/ml or below. 3) H. influenzae
      The activities of all drugs were potent against H. influenzae tested with MIC80s
      of 4 micrograms/ml or below. Cefotiam (CTM), cefmenoxime (CMX), cefditoren (CDTR)
      and ofloxacin (OFLX) showed the most potent activities with MIC80s of 0.063
      microgram/ml. 4) P. aeruginosa (mucoid strains) Tobramycin (TOB) showed the most
      potent activity against P. aeruginosa (mucoid strains) with MIC80 of 1
      microgram/ml. Ceftazidime (CAZ), cefsulodin (CFS), IPM, gentamicin (GM), ABK and
      ciprofloxacin (CPFX) showed the next potent activities, with MIC80s of 2
      micrograms/ml. The MIC80s of the other drugs ranged from 4 micrograms/ml to 16
      micrograms/ml. 5) P. aeruginosa (non-mucoid strains) TOB and CPFX showed the most
      potent activities against P. aeruginosa (non-mucoid strains) with MIC80s of 1
      microgram/ml. The MIC80s of piperacillin (PIPC) and cefoperazone (CPZ) were 16
      micrograms/ml in 1995, and they were 64 micrograms/ml in 1996. 6) K. pneumoniae
      All drugs except ampicillin (ABPC) were active against K. pneumoniae. CMX,
      cefpirome (CPR), cefozopran (CZOP) and carumonam (CRMN) showed the most potent
      activities against K. pneumoniae with MIC80s of 0.125 microgram/ml. The MIC80s of
      the other drugs ranged from 0.25 microgram/ml to 2 micrograms/ml. 7) M.(B)
      catarrhalis Against M.(B.) catarrhalis, all drugs showed good activities with
      MICs of 4 micrograms/ml or below. IPM and minocycline (MINO) showed the most
      potent activities with MICs of 0.063 microgram/ml. Also, we investigated year to
      year changes in the characteristics of patients, their respiratory infectious
      diseases, and the etiology. Patients' backgrounds were examined for 557 isolates
      from 449 cases. The examination of age distribution indicated that the proportion
      of patients with ages over 60 years was 71.0% of all the patients showing a
      slight increase over that in 1994. Proportions of diagnosed diseases were as
      follows: Bacterial pneumonia and chronic bronchitis were the most frequent with
      35.9% and 30.3% respectively. They were followed by bronchiectasis with a
      proportion of 10.

PMID- 9755431
TI  - [Evaluation of antibacterial activities of various antibiotics against glucose
      non-fermentative gram-negative rods other than Pseudomonas aeruginosa].
AB  - MICs of piperacillin, sulbactam/cefoperazone, minocycline (MINO), gentamicin,
      amikacin, flomoxef, ceftazidime, cefozopran, cefsulodin and imipenem were
      determined, against 189 clinical isolated strains of glucose non-fermentative
      Gram-negative Rods (NFGNR; Acinetobacter baumannii (44), Alcaligenes faecalis
      (5), Alcaligenes xylosoxidans (25), Burkholderia cepacia (12), Chryseobacterium
      indologenes (23), Chryseobacterium meningosepticum (9), Pseudomonas fluorescens
      (8), Pseudomonas putida (12), Stenotrophomonas maltophilia (51). Most species of
      these NFGNR show resistance to many antibiotics tested. Among the antibiotics
      used in this study, the only antibiotic effective against all species of NFGNR
      tested is MINO. The spectrums of antibacterial activities of various antibiotics
      determined by MICs may be useful in preliminary test for identification of these
      NFGNR.

PMID- 9755433
TI  - [Resistance to macrolide antibiotics found in methicillin-resistant Japanese
      clinical isolates of Staphylococcus aureus in 1996].
AB  - Minimum inhibitory concentrations (MICs) of erythromycin, clarithromycin,
      roxithromycin, oleandomycin, triacetyloleandomycin, azithromycin, josamycin and
      midecamycin were investigated using 200 strains of methicillin-resistant
      Staphylococcus aureus (MRSA) clinically isolated in Japan during 1996. The
      results show that the MRSAs could be classified into five groups according to MIC
      patterns to various macrolides and that more than 88% of the strains used were
      highly-resistant to all macrolides tested. It was found that 9.0% of the strains
      examined showed a unique MIC pattern different to that of macrolide-lincosamide
      streptogramin B antibiotic resistance type. This group was found to be highly
      resistant to 14-membered but susceptible to 16-membered macrolides. The
      resistance induction by erythromycin or oleandomycin was observed to increase for
      clarithromycin and roxithromycin resistances in a part of strains used. On the
      other hand, for azithromycin, such induction was not observed.

PMID- 9755434
TI  - Indium-111 satumomab pendetide: the first FDA-approved monoclonal antibody for
      tumor imaging.
AB  - OBJECTIVE: Colon cancer is the second most common cause of cancer mortality.
      Ovarian cancer is the most common gynecologic malignancy cause of death in women.
      A labeled monoclonal antibody attaches to a tumor-associated antigen and allows
      these tumor masses to be imaged or treated, depending on the radionuclide used.
      Indium-111 satumomab pendetide was the first labeled monoclonal antibody to be
      approved by the Food and Drug Administration (FDA) for tumor imaging. It is
      reactive with most colorectal and ovarian cancers, as well as other cancers.
      After reading this article, the technologist will understand the FDA approval
      process, phase trial results, safety and adverse reactions, human antimurine
      antibody response, indications, imaging protocol, and strengths and weaknesses of
      imaging with satumomab pendetide. Representative cases are presented.

PMID- 9755435
TI  - Nuclear cardiology, Part III: Scintigraphic evaluation of cardiac perfusion.
AB  - OBJECTIVE: After reading Part III of this series of nuclear cardiology articles,
      the technologist should be able to: (a) compare and contrast radiopharmaceuticals
      used for myocardial perfusion imaging; (b) describe imaging protocols used for
      detecting coronary artery disease; and (c) describe imaging patterns seen
      following reconstruction of myocardial images.

PMID- 9755437
TI  - Effects of the attenuation map used in the Chang algorithm on quantitative SPECT
      results.
AB  - OBJECTIVE: This study examined the effects on SPECT quantitation caused by
      erroneous size and position of the attenuation map and inaccurate pixel size used
      in the Chang algorithm. METHODS: Projection data of a three-dimensional head
      phantom were simulated with a uniform attenuation coefficient of 0.15/cm for the
      inside of the phantom. Images were reconstructed using the filtered
      backprojection algorithm without attenuation compensation and the Chang algorithm
      with different attenuation maps. Quantitative comparison then was performed
      between the reconstructed images and the phantom. RESULTS: The pixel values
      obtained for noisy data by using the first-order Chang algorithm with an accurate
      attenuation map were less than 10% different from the true values and the left
      right asymmetry was under 5%. Small errors in the geometric parameters of the
      attenuation map, however, caused considerable quantitative inaccuracy in the
      reconstructed image. For example, a 0.64-cm error in the size of the map caused
      10% deviation from the true value and a 0.64-cm shift of the position of the map
      towards the left produced 10% left-right pixel value asymmetry. CONCLUSION: The
      accuracy of the Chang algorithm critically depends on the geometric parameters.
      For a uniform attenuator with symmetric geometry, such as the human brain, a true
      left-right symmetry in the pixel value can be altered significantly by a small
      error in the geometric parameters, while symmetry can be maintained with no
      attenuation compensation.

PMID- 9755436
TI  - Dual-isotope protocol for indium-111 capromab pendetide monoclonal antibody
      imaging.
AB  - OBJECTIVE: A dual-isotope imaging protocol using 99mTc-labeled red blood cells
      with 111In capromab pendetide monoclonal antibody imaging for detective and
      localizing nodal metastasis in prostate cancer is described. METHODS: This
      protocol involves a single SPECT acquisition that is less time consuming and more
      comfortable for the patient than the currently recommended method, which requires
      two separate SPECT acquisitions performed on different days. RESULTS: Forty
      patients were studied with the dual-isotope protocol. Preliminary data suggest
      increased accuracy compared with the single-isotope technique. CONCLUSION: The
      dual-isotope technique assures the precise image registration needed for accurate
      comparison of blood pool and pelvic lymph node activity that is required for
      confident and accurate image interpretation.

PMID- 9755438
TI  - Effect of time on liver clearance of technetium-99m-tetrofosmin in patients with
      acute chest pain: when should imaging begin?
AB  - OBJECTIVE: Due to stable myocardial retention and technetium imaging
      characteristics, 99mTc-tetrofosmin has been considered potentially useful for
      acute chest pain imaging. Tetrofosmin also has favorable biokinetics with
      reported rapid liver clearance, 5 min poststress and 30-45 min post-rest
      injection. Since comparable data are not available, the effect of time on liver
      clearance was evaluated in patients with acute chest pain. METHODS: One hundred
      six patients received an intravenous injection of 25-30 mCi 99mTc-tetrofosmin to
      evaluate acute chest pain. SPECT imaging was performed 15-120 min after injection
      of the tracer. Patient images were grouped according to the time of acquisition
      after acute injection: 15-30 min, 31-45 min, 46-60 min, 61-90 min and > 90 min.
      Quantitative analysis was performed of a similar anterior projection for each
      patient consisting of 6 X 6-pixel region of interest over the myocardium and
      adjacent liver. Average counts per pixel were determined and a heart/liver (H/Li)
      ratio was calculated. RESULTS: The mean H/Li ratio was < 1.0 for patient images
      acquired 15-45 min after injection, and > 1.0 for patient images acquired after
      45 min. The difference was statistically significant (p < 0.05). CONCLUSION:
      Quantitative analysis suggests that the optimal imaging time should be at least
      45 min after the injection of 99mTc-tetrofosmin to allow adequate liver clearance
      before image acquisition of acute chest pain syndromes.

PMID- 9755439
TI  - Measurement of blood radioactivity for quantification of cerebral blood flow
      using a gamma camera.
AB  - OBJECTIVE: This study was designed to determine whether gamma cameras can be
      substituted for well-type scintillation counters in measuring blood radioactivity
      counts to be used as an input function for the quantitative measurement of
      cerebral blood flow (CBF). METHODS: Twelve different aqueous 123I solutions were
      prepared by serial dilution of the original concentration of 281.9 kBq/ml, and
      the radioactivity count of each dilution was measured with a gamma camera with
      the collimator removed, and with a well-type scintillation counter. When
      measuring the radioactivity counts with a gamma camera, static images were
      acquired using a 128 x 128 matrix for 5 min, and the regions of interest with 14
      x 14 pixels (21 mm x 21 mm) were defined. RESULTS: There was a good correlation
      between the results obtained by these two procedures in the range of
      concentration between 0.008 kBq/ml and 281.9 kBq/ml (y = 4.245x-2.549, r = 1.0, n
      = 12, s.e.e. = 7.217 kcpm). There was good agreement between the CBF values
      (ml/100 g/min) obtained using the cross-calibration factor (CCF) and blood
      radioactivity counts measured with the two procedures (y = 0.990x + 0.552, r =
      0.990, n = 231, s.e.e. = 1.340 ml/100 g/min). CONCLUSION: The results suggest
      that gamma cameras can be substituted for well-type scintillation counters in the
      quantitative measurement of CBF, and make it unnecessary to measure CCF after
      routine calibration of a SPECT apparatus.

PMID- 9755440
TI  - Adsorption of some technetium-99m radiopharmaceuticals onto disposable plastic
      syringes.
AB  - OBJECTIVE: The purpose of this study was to determine the adsorption behavior of
      some widely used, commercially available 99mTc radiopharmaceuticals onto
      different types of plastic syringes. METHODS: Kits were reconstituted with 99mTc
      pertechnetate diluted with 0.9% saline to produce maximum radioactive
      concentrations, as stated by the manufacturers. Aliquots of the solutions were
      transferred to four different brands of 2-ml syringes. The activity in the
      syringes was measured before and after injections or simulated injections. The
      amount adsorbed to the plastic syringe barrel and plunger before and after
      washout also was measured at different time intervals. Comparisons between
      products from different manufacturers were made for 99mTc succimer (DMSA) and
      99mTc macroaggregated albumin (MAA). RESULTS: Some 99mTC preparations undergo
      significant adsorption to plastic syringes. Adsorption differs considerably
      between products from different manufacturers. There was significantly higher
      residual activity in some types of syringes. In some cases the residual was as
      high as 40%-50% of the initial activity, and most of the adsorption occurred
      within 15 min of filling the syringe. CONCLUSION: The data suggest that the
      extent of adsorption depends on pharmaceutical excipients in the kits and/or the
      type of syringe used. When inappropriate syringes are used, the reduction in the
      administered activity may result in poor-quality images. Therefore, the
      compatibility between radiopharmaceutical and syringe should be investigated
      under normal conditions of preparation and use every time a new brand of syringe
      or a new radiopharmaceutical comes into use in diagnostic nuclear medicine.

PMID- 9755441
TI  - The incidence of blood contamination of lead unit dose containers with and
      without single-use protective inserts used with commercially prepared
      radiopharmaceutical unit doses.
AB  - OBJECTIVE: This investigation evaluated the effectiveness of disposable plastic
      inserts in radiopharmaceutical unit dose lead containers (pigs) in preventing the
      distribution of doses in blood-contaminated containers. Technologists commonly
      dispose of the syringes by placing them into the lead pigs, leaving the needles
      uncapped. This process raises the question of unsuspected blood contamination of
      these pigs. Consequently, the distribution of commercially prepared
      radiopharmaceutical doses in reusable lead pigs may result in radiopharmaceutical
      doses being distributed in containers that are contaminated with blood. METHODS:
      Using a simple chemical wipe test designed to determine the presence or absence
      of blood contamination, 618 pigs from commercial radiopharmacies throughout the
      U.S. were tested for contamination. The inside of the pigs and inserts, if
      present, were wiped before and after dose administration. Of the pigs tested, 292
      came from radiopharmacies that used a protective, disposable plastic insert
      inside the pig, and 326 came from radiopharmacies that did not use an insert.
      RESULTS: Of those pigs without the protective disposable inserts, 39.3% arrived
      in the nuclear medicine department in pigs contaminated with blood. Of those pigs
      with inserts, 1% arrived with blood-contaminated inserts. After dose
      administration, 46.3% of the pigs without inserts were contaminated with blood
      and 3% of the protective inserts were contaminated. CONCLUSION: The proper use of
      disposable plastic inserts reduces the possibility of distributing
      radiopharmaceutical unit doses in containers contaminated with blood.

PMID- 9755442
TI  - A safe, simple method for preparing heat-damaged red cells for diagnosing splenic
      infarct or trauma.
AB  - OBJECTIVE: The purpose of this study was to demonstrate a fast, safe and simple
      method for preparing heat-damaged red blood cells. METHODS: Patient blood was
      radiolabeled using the Ultra-Tag RBC kit and then heated to 49.5 degrees C for 20
      min. The reaction vial was cooled in ice water for 1 min and the required
      activity was administered to the patient. The patient was imaged 60 min
      postinjection. RESULTS: High-quality planar and SPECT images of the spleen were
      obtained with low background activity noted. Radiolabeling efficiency was greater
      than 95%. CONCLUSION: The method was safe and simple to perform. High-quality
      images of the spleen were obtained.

PMID- 9755443
TI  - Radiation safety when a patient dies after therapy.
AB  - OBJECTIVE: When a patient dies a short time after radionuclide therapy, several
      issues arise due to the shifting of responsibility from patient care to
      protection of the public, while respecting societal values and rites. Such a
      situation occurred in our institution after administering a large therapeutic
      dose of 131I for metastatic thyroid cancer. The requirements of safe practice,
      the shift accountability, the ethical aspects and forthcoming changes in the
      regulatory constraints are discussed.

PMID- 9755444
TI  - 'Nano-dumpling' with drug delivery potential.

PMID- 9755445
TI  - Cost-effective carbohydrate synthesis permits large-scale production of an anti
      inflammatory drug.

PMID- 9755446
TI  - Combining strategies to improve non-viral vectors.

PMID- 9755447
TI  - Early-warning cancer tests in development.

PMID- 9755448
TI  - Cancer vaccines '98: a reductionistic approach. Bethesda, MD, USA, 27-28 April
      1998.

PMID- 9755449
TI  - Multiple sclerosis: modelling the future. The Multiple Sclerosis Society of Great
      Britain and Northern Ireland Conference: Frontiers in Science and Patient Care
      Disease Management.

PMID- 9755451
TI  - Data disclosure in the human genome project.

PMID- 9755450
TI  - Tuberculosis research comes of age. Keystone Symposium on Tuberculosis: Molecular
      Mechanisms and Immunologic Aspects.

PMID- 9755452
TI  - Restricted inflammatory reaction in the CNS: a key impediment to axonal
      regeneration?
AB  - Axons in the central nervous system (CNS) of adult mammals do not regenerate
      after injury. Mammalian CNS differs in this respect from other mammalian tissues,
      including the peripheral nervous system (PNS), and from the CNS of lower
      vertebrates. In most parts of the body, including the nervous system, injury
      triggers an inflammatory reaction involving macrophages. This reaction is needed
      for tissue healing; when it is delayed or insufficient, healing is incomplete.
      The CNS, although needing an efficient inflammatory reaction resembling that in
      the periphery for tissue healing, appears to have lost the ability to supply it.
      We suggest that restricted CNS recruitment and activation of macrophages are
      linked to regeneration failure and might reflect the immune privilege that
      characterizes the mammalian CNS. As macrophages play a critical role in tissue
      restoration, and because their recruitment and activation are among the most
      upstream of the events leading to tissue healing, overcoming the deficiencies in
      these steps might trigger a self-repair processing leading to recovery after CNS
      injury.

PMID- 9755454
TI  - Congenital heart defects and 22q11 deletions: which genes count?
AB  - Hemizygous deletions on the long arm of chromosome 22 (del22q11) are a relatively
      common cause of congenital heart disease. For some specific heart defects such as
      interrupted aortic arch type B and tetralogy of Fallot with absent pulmonary
      valve, del22q11 is probably the most frequent genetic cause. Although extensive
      gene searches have been successful in discovering many novel genes in the deleted
      segment, standard positional cloning has so far failed to demonstrate a role for
      any of these genes in the disease. We show how the use of experimental animal
      models is beginning to provide an insight into the developmental role of some of
      these genes, while novel genome manipulation technologies promise to dissect the
      genetic aspects of this complex syndrome.

PMID- 9755453
TI  - Human developmental disorders and the Sonic hedgehog pathway.
AB  - Sonic hedgehog (Shh) is a morphogen that is crucial for normal development of a
      variety of organ systems, including the brain and spinal cord, the eye,
      craniofacial structures, and the limbs. Mutations in the human SHH gene and genes
      that encode its downstream intracellular signaling pathway cause several clinical
      disorders. These include holoprosencephaly (HPE, the most common anomaly of the
      developing forebrain), nevoid basal cell carcinoma syndrome, sporadic tumors,
      including basal cell carcinomas, and three distinct congenital disorders: Greig
      syndrome Pallister-Hall syndrome, and isolated postaxial polydactyly. These
      conditions caused by abnormalities in the SHH pathway demonstrate the crucial
      role of SHH in complex developmental processes, and molecular analyses of these
      disorders provide insight into the normal function of the SHH pathway in human
      development.

PMID- 9755455
TI  - Transcription-factor-modulating agents: precision and selectivity in drug design.
AB  - Transcription factors play an important role in the long-term regulation of cell
      growth, differentiation and responses to environmental cues. There is growing
      evidence that these proteins are closely associated with control at the genetic
      level of the development and maintenance of the diseased state, and might
      therefore provide selective targets for novel pharmaceutical intervention. The
      vast array of information available on the three-dimensional structure of
      transcription factors and the intricate molecular machineries that fine-tune
      their activity offer opportunities for embarking on the rational design of drugs
      directed against specific transcription factors, thus producing potent new agents
      that modulate their function in a plethora of clinically important situations.

PMID- 9755457
TI  - [Genetic polymorphism of drug metabolizing enzymes: new mutations in CYP2D6 and
      CYP2A6 genes in Japanese].
AB  - Interindividual variation of drug effects in humans can be attributed to many
      factors. Among the factors, the rate of drug metabolism has been regarded as the
      most important one. A genetic defect of enzymes involved in drug metabolism,
      particularly cytochrome P450 (CYP), has been believed to be one of the important
      causal factors of adverse drug reactions. There are multiple gene mutations for
      CYP causing the poor metabolizer phenotype. The occurrence of genetic
      polymorphism has been seen in genes for CYP1A1, CYP2A6, CYP2C9, CYP2D19, CYP2D6,
      CYP2E1 and CYP3A5. Among them, the molecular mechanisms of genetic polymorphisms
      of CYP2D6 (debrisoquine/sparteine type) and CYP2A6 (coumarin type) in Japanese
      have been the focus of investigations. Only 20-30% of the Japanese population
      that shows the CYP2D6 poor metabolizer phenotype can be diagnosed by gene
      analysis. By other means, we found two new mutations, CYP2D6/J9 and CYP2D6/C8, in
      Japanese. With regard to CYP2A6, we discovered SM-12502, a new probe drug in
      addition to coumarin, that is currently under development; this drug is mainly
      metabolized by CYP2A6. Using this drug as a probe, we found poor metabolizers and
      analyzed the genes for CYP2A6. We found a new mutation (CYP2A6 whole deletion)
      responsible for the poor metabolizer phenotype. These results should contribute
      to the selection of an effective drug prescription and a reduced incidence of
      adverse effects.

PMID- 9755458
TI  - [Genetic polymorphism of the CYP2C subfamily].
AB  - Cytochromes P450 (CYP) are a superfamily of hemoproteins that metabolize various
      foreign compounds. The human CYP2C subfamily is one of the subfamilies of the
      CYP2 family and it consists of four members of CYP isoforms, CYP2C8, CYP2C9,
      CYP2C18 and CYP2C19. A well-characterized genetic polymorphism occurs in CYP2C19,
      which is associated with the 4'-hydroxylation of S-mephenytoin. There are two
      phenotypes, extensive metabolizers and poor metabolizers (PM) of mephenytoin. The
      frequency of PM in the Japanese population is 20%, while only 3% of Caucasians
      are PM of mephenytoin. Two defective alleles, designated as CYP2C19*2 and
      CYP2C19*3, have been described, and the latter mutation has been detected only in
      Oriental populations. Recently, an allelic variant of CYP2C9 that causes
      substitution of Leu359 for Ile359 has been shown to be associated with the
      decreased metabolic clearance of various therapeutic agents including warfarin,
      tolbutamide and phenytoin. The frequency of this variant allele in the Japanese
      population is 2%, while those of the Caucasians are 6-9%. Although the role of
      CYP2C18 in the drug metabolism remains obscure, we have recently found that
      defective alleles of CYP2C19*3 and CYP2C18m1 are completely linked, suggesting
      that PM of CYP2C19 with CYP2C19*3 alleles is a PM of CYP2C18 and vice versa.

PMID- 9755459
TI  - [The physiological role of P450-derived arachidonic acid metabolites].
AB  - Arachidonic acid is metabolized to biologically active substances by three major
      enzyme systems including cyclooxygenases, lipoxygenases and cytochrome P450s. The
      third pathway, P450-dependent pathway, includes allylic oxidation, omega
      hydroxylation, and epoxidation of arachidonic acid. Of these metabolites, the
      physiological role of 20-hydroxyeicosatetraenoic acid (20-HETE) produced by CYP4A
      isoforms has been extensively studied. 20-HETE affects ion transport, constricts
      blood vessels and participates in tubuloglomerular feed back. Increased
      production of 20-HETE is a major factor in elevating blood pressure in
      spontaneously hypertensive rats (SHR). We have found that CYP4A2 level in SHR is
      much higher than that of normotensive rat. Recently, factors of endothelial
      origin other than nitric oxide and prostaglandins were reported. Inhibitors of
      P450-dependent arachidonic acid metabolism greatly reduce the vasodilator effect
      and this factor is speculated to be an epoxide of arachidonic acid. We have
      isolated CYP2C23 from rat kidney and have found that it produces arachidonic acid
      epoxides. We have investigated changes in the CYP2C23 levels in physiological and
      pathophysiological conditions. Multiple pathways of arachidonic acid metabolism
      by P450 have been reported and the diverse properties of these metabolites and
      the wide distribution of the P450 system make them prime candidates for
      participation in regulatory mechanisms of the circulation and transporting
      epithelia.

PMID- 9755460
TI  - [Inhibition of cytochrome P450 by nitric oxide].
AB  - Nitric oxide (NO) reacts with iron, superoxide, thiols and oxygen. Although NO
      reversibly interacts with the heme-iron of P450, the pathophysiological role of
      this interaction remains to be elucidated. We found that hepatic levels of P450
      markedly decreased in endotoxemic rats, particularly when the rate of NO
      generation was increased. To determine the possible role of NO in the modulation
      of the structure and function of P450, changes in the levels and activities of
      P450 isozymes were determined in liver microsomes from normal and endotoxemic
      rats. Electron spin resonance analysis revealed that incubation of microsomes
      with the NO donor NOC-7 rapidly generated NO-P450 adducts. Microsomal levels of
      NO-P450 adducts increased and peaked at 10 min after incubation and decreased
      thereafter; it disappeared completely within 60 min. In contrast, microsomal
      levels of the low-spin ferric form and CO-differential spectrally detectable P450
      rapidly decreased during the initial 10 min; the signal intensity for P450
      recovered thereafter. Western blot analysis using specific antibodies against
      CYP3A2 and CYP2C11 isozymes revealed no detectable degradation of these isoforms.
      Effect of NO on the catalytic activity of the enzymes was also determined by
      using testosterone as the substrate. The hydroxylation activity in microsomes
      rapidly decreased during the initial 10 min and disappeared slowly thereafter.
      These results suggested that NO might form dissociable complexes with the heme
      moiety of P450 and irreversibly inactivate them. The mechanism for P450
      inactivation by NO and the role of NO-P450 interaction in the pathogenesis of
      liver injury in endotoxemia are discussed.

PMID- 9755461
TI  - [The regulation of steroidogenesis by 17 alpha-hydroxylase/17,20-lyase
      (P450c17)].
AB  - Cytochrome P450c17 (P450c17) catalyzes 17 alpha-hydroxylation and 17, 20-lyase
      reactions. This enzyme plays a key role in determination of the balance between
      glucocorticoids and steroid sex hormones. In this review we discuss recent
      progress in the studies of both transcriptional regulation of CYP17 encoding
      P450c17 and enzymatic regulation of P450c17. Several transcription factors
      involved in cAMP-dependent transcription of the gene have been isolated and
      identified to be members of the atypical homeodomain "TALE" superfamily
      containing Pbx, Meis, Pknox and TGIF families. The studies of enzymatic
      regulation of P450c17 suggest that cytochrome b5 (b5), a heme protein, may switch
      the reaction of P450c17 by enhancing the 17, 20-lyase activity to increase the
      level of plasma C19 steroids. The importance of b5 in the synthesis of C19
      steroids has also been shown in a clinical study reporting that the external
      genitalia was abnormal in a patient having a defect in b5. Therefore, this
      enhancement by b5 on the lyase activity of P450c17 may be essential to normal
      sexual differentiation in humans and also important in control of an optimal
      balance between sex steroid hormones and glucocorticoids. In addition, the age
      dependent expression of P450c17 in immature rat livers is also discussed.

PMID- 9755462
TI  - [A new aspect of the pharmacological and physiological significance of the
      aromatase/estrogen system].
AB  - Aromatase (estrogen synthetase) catalyzes a key step in estrogen biosynthesis and
      plays an important role in reproductive processes in the ovary and placenta. In
      this context, aromatase is an enzyme producing estrogen as an endocrine female
      sex hormone. Recently, it has reported that aromatase is also present in various
      extra-gonadal tissues and is tissue-specifically regulated by various factors.
      This tissue-specific regulation of human aromatase gene is realized by
      alternative utilization of multiple exon 1's; exons la, 1b, 1c, 1d, 1e, and 1f
      that are specific for expression in the placenta, skin fibroblasts/fetal liver,
      ovary, ovary/prostate/testis, placenta, and brain, respectively. Each of the
      tissue-specific exon 1's is flanked by a unique promoter containing basic and
      regulatory elements. The facts that (i) aromatase is distributed in various
      gonadal and extra-gonadal tissues and (ii) regulated tissue-specifically by
      various factors, (iii) estrogen participates in specific physiological functions
      of various tissues, and (iv) estrogen receptor is also distributed in various
      tissues strongly indicate that estrogen locally produced by aromatase acts in
      various tissues as a multi-functional paracrine or autocrine hormone. This idea
      was discussed in connection with the Kd value for the estrogen receptor and serum
      concentration of estrogen.

PMID- 9755463
TI  - [Production of various antibodies and single chain Fv molecule against signal
      transducing proteins].
AB  - In the present review, we described the procedures of production of polyclonal
      and monoclonal antibodies and single chain Fv molecule (scFv). Among several
      animal species, the rabbit is the best animal for polyclonal antibody production
      and the mouse is the best animal for monoclonal antibody production. In this
      review, we discussed problems that might be encountered when trying to produce
      antibodies. Polyclonal antibodies are easily produced in rabbits by immunizing
      them with glutathione-S-transferase fusion proteins. However, it is difficult to
      eliminate nonspecifically reacting antibodies, even after the antibodies were
      purified from sera by an antigen column. Monoclonal antibody production is a time
      consuming process, but it successful, will produce a very useful reagent due to
      no limitation of supply and constant quality. We described monoclonal antibody
      production by means of glutathione-S-transferase fusion protein. scFv is a
      portion of the antibody and is constructed by PCR of VH and VL regions of the
      antibody. We recommend that scFv should be constructed from a hybridoma that
      secretes monoclonal antibody, although some researchers have claimed that scFv
      can be constructed from the spleen of immunized mice. The expression of scFv is a
      promising approach to analyze the function of one of the subtypes, when the
      original monoclonal antibody can block the function of the protein.

PMID- 9755464
TI  - [Effects of personality, cognitive, and situational variables on risk taking
      behavior].
AB  - This study examined the effects of individual difference and situation on risk
      taking behavior. In Experiment 1, 115 undergraduates completed a questionnaire of
      personality (sensation seeking, optimism, etc.) and their risk taking behavior,
      risk perception, and anxiety in eight situations: personal, social, gain-loss,
      and loss situations. Results indicated an effect of personality on risk taking
      behavior in personal gain-loss situations (sports and life event), which was
      mediated by perceived risk controllability. In Experiment 2, 137 undergraduates
      completed a questionnaire of personality, cognitive variables (risk perception,
      own competence, and perceived cost and benefit), and risk taking behavior in
      personal gain-loss situations (sports, life event, and gambling). Results of
      covariance structure analysis showed that perceived risk controllability affected
      the relationship between the variables. For instance, risk significance and
      perceived cost and benefit mediated the effect of 'controllability with skills'
      on risk taking behavior in the controllable situation (e.g., sports). Similarly,
      competence and risk perception mediated the effect of 'uncontrollable luck
      factors' in the chance situation (e.g., life event).

PMID- 9755465
TI  - [The effects of media violence on affective, cognitive, and physiological
      reactions of viewers].
AB  - The present study investigated the effects of media violence on affective,
      cognitive, and physiological reactions of viewers. Eighty undergraduate student
      (male = 40, female = 40) participated in the experiment. First, subjects were
      exposed to one of four violent films whose levels of violence and entertainment
      were based on ratings taken in a previous study (Yoshida & Yukawa, 1996).
      Immediately after viewing the film, subjects described their thoughts which
      occurred during watching the film and rated their affective reactions toward the
      film. Heart rate and eyeblink rate as indicators of physiological arousal were
      measured continuously before, during, and after the film. Results showed that the
      film high in violence elicited more negative and empty-powerless affects, while
      the film high in entertainment evoked more positive affects.

PMID- 9755466
TI  - [Delays in recognizing facial expressions resulting from prolonged viewing of
      adaptation face stimuli].
AB  - The main purpose of the present study was to investigate the mechanism underlying
      fundamental dimensions in recognition of facial expressions, using the prolonged
      viewing method. Pictures of female faces were used, which displayed one of the
      following six: happiness, sadness, surprise, anger, disgust, and neutral
      expressions. In Experiment 1, the mean ratings of each expression on each picture
      were analyzed with principal component analysis (PCA). In Experiment 2, subjects
      orally judged the expressions of test faces following either one or 25 seconds of
      viewing of an adaptation face. Significant delays occurred in the prolonged
      viewing condition only when the adaptation face had a higher absolute value on
      'pleasantness' the first component of PCA, than the test face. In contrast,
      adaptation faces that were high only on 'arousal,' the second component, produced
      no such effects. It was suggested that there are at least two subsystems involved
      in the recognition of facial expressions and that each system has different
      temporal characteristics.

PMID- 9755467
TI  - [Preference for high frequency sounds of contact calls in primates: Japanese
      macaques and ringtailed lemurs].
AB  - Preference for high frequency sounds in human infants are found by other
      researchers. The purpose of this study is to examine whether nonhuman primates
      also have the same tendency as human infants. It is important to consider
      language origins. Two types of tape recorded coo calls, contact calls, with high
      and low fundamental frequencies were played back as stimuli for two groups of
      Japanese macaques (Macaca fuscata). The result showed that the animals of both
      groups preferred high frequency sounds. To ascertain whether other species also
      have the same tendency as the Japanese macaques, a playback experiment similar to
      that for Japanese macaques was conducted for one group of ringtailed lemurs
      (Lemur catta). Tape recorded mew calls, contact calls, were used as stimuli. The
      results showed that ringtailed lemurs also preferred high frequency sounds.
      Moreover, it was clarified by an additional playback experiment for one group of
      Japanese macaques that animals had an affective preference for high frequency
      sounds. These results suggest that nonhuman primates have a consistent tendency
      to prefer high frequency sounds.

PMID- 9755468
TI  - [Effects of modality on rats' short-term memory in successive matching-to-sample
      task].
AB  - This study examined the effects of modality on rats' short-term memory by using
      the go/no-go delayed paired stimuli comparison task (Konorski task). Each of
      paired stimuli (S1, S2) was successively presented in order with delay intervals,
      and a food pellet was contingent upon the lever pressing only when S2 matched S1
      (light; L or tone; T). The accuracy of discrimination between the matched and
      nonmatched pairs decreased as a function of delay interval. Steeper forgetting
      was shown when a visual stimulus was presented as S1 (S1-L trials) than when an
      auditory S1 (S1-T trials) was presented. The longer was the ITI duration, the
      better was the performance in the S1-T trials, but this was not true for the S1-L
      trials. Further, discrimination performance was an increasing function of the
      duration of S1 regardless of the modality of S1. These results were discussed
      mainly on the basis of interference theory and decay theory of forgetting.

PMID- 9755469
TI  - [Preschooler peer interaction and performance on Doise spatial task].
AB  - Using Doise spatial task, this study examined the following three hypotheses
      about preschoolers' attainment of spatial skills: (1) A different viewpoint
      promotes faster advancement through developmental levels of spatial skills than
      the same viewpoint. (2) An interaction partner with a different skill level,
      rather than the same level, promotes faster advancement. And (3) a socio
      cognitive conflict with the partner promotes faster advancement. To test these
      hypotheses, the method of Doise and Mugny (1984) was used in Experiment 1. In
      Experiment 2, the method was modified in several ways. Most notably by pointing
      out and changing the shape of the marker, and by decreasing the number of objects
      to be arranged. Results of the experiments supported Hypothesis 3, but not 1 or
      2. It was concluded that socio-cognitive conflicts in preschooler peer
      interaction contributed to children's development of spatial skills.

PMID- 9755470
TI  - [Determinants of time-monitoring on prospective memory tasks].
AB  - The purpose of this study was to examine determinants of time-monitoring to
      clarify the cognitive process in prospective memory tasks (i.e., tasks which
      require the timely execution of a previously intended action). Thirty-two
      participants were asked to perform future activities three minutes after the
      start of background tasks, and their time-monitoring responses were recorded. The
      results showed that higher motivation and less cognitive load led to higher time
      monitoring frequency and better performance in prospective memory tasks. However,
      with time presentation, time-monitoring frequency could be reduced, while the
      performance in prospective memory tasks was improved. The findings indicate that
      information which facilitates the maintenance of inner time model is an important
      factor for effective time-monitoring. This study suggested that frequency of time
      monitoring could be regarded as a critical factor in the theoretical analysis of
      prospective memory tasks.

PMID- 9755471
TI  - [Subjective well-being and self acceptance].
AB  - The purpose of the present study was to examine the relationship between
      subjective well-being and self acceptance, and to design a happiness self-writing
      program to increase self acceptance and subjective well-being of adolescents. In
      study 1, we examined the relationship between social interaction and self
      acceptance. In study 2, we created a happiness self-writing program in cognitive
      behavioral approach, and examined whether the program promoted self acceptance
      and subjective well-being. Results indicated that acceptance of self-openness, an
      aspect of self acceptance, was related to subjective well-being. The happiness
      self-writing program increased subjective well-being, but it was not found to
      have increased self acceptance. It was discussed why the program could promote
      subjective well-being, but not self acceptance.

PMID- 9755472
TI  - [Contingent negative variation (CNV) in the detection of deception task using a
      serial presentation of pictures].
AB  - The purpose of the experiment was to investigate the feasibility of using
      contingent negative variation (CNV) as an index of detection of deception. Twelve
      subjects were required to complete both an innocent and guilty condition in that
      order. In the innocent condition, a series of six pictures, two of which depicted
      different landscapes and four others which depicted different female faces, was
      presented repeatedly on a computer display. Subjects responded by pressing a
      button following the landscape picture (target stimulus) that was presented last
      in the sequence. In the guilty condition, the procedures were the same except
      that subjects were also required not to detect one of the female pictures in mind
      (critical item), which they had chosen after the completion of the innocent
      condition. As compared with the innocent condition, the CNV amplitudes decreased
      significantly immediately before the target stimulus in the guilty condition
      where subjects had to conceal the critical item. The implication of these data
      both for the psychological completion of the concealed task and the practice in
      the field were discussed.

PMID- 9755473
TI  - Comparison of proteolytic enzyme activities in adults of insecticide resistant
      and susceptible strains of the housefly M. domestica L.
AB  - Intracellular proteolytic activity in a DDT-resistant and a susceptible strain of
      M. domestica was determined by assaying a comprehensive range of cytoplasmic and
      lysosomal enzymes. The resistant strain showed significantly higher protease
      activities in whole body, head, thorax, abdomen and gut homogenates compared to
      the susceptible strain. The activity of alanyl- and arginyl aminopeptidase from
      both strains increased substantially after topical treatment with DDT at 1, 2 and
      3 h, suggesting an involvement of proteolytic enzymes in the induction of
      detoxifying enzymes, thus indicating a possible role of the intracellular
      proteolytic activities in the resistance mechanism.

PMID- 9755474
TI  - Isolation, sequence determination, physical and physiological characterization of
      the neuroparsins and ovary maturing parsins of Schistocerca gregaria.
AB  - Neurosecretory products immunologically related to either neuroparsin (NP) or
      ovary maturing parsin (OMP) of Locusta migratoria (Lom) were purified from the
      nervous corpora cardiaca of Schistocerca gregaria (Scg). The determination of
      both their molecular masses by mass spectrometry and their sequences by automated
      Edman degradation established that they are members of the NP and OMP families
      respectively. NP molecules of Schistocerca (Scg NPs) consisted of two major forms
      having about the same molecular masses as NPA and NPB of Locusta and 88% primary
      structure similarity. They had also the same antidiuretic activity. OMP molecules
      of Schistocerca (Scg OMPs) were composed in young adults of four isoforms: two
      long isoforms corresponding to Lom OMP, and differing by a tripeptide insertion
      (Pro-Ala-Ala) at position 21 and two short isoforms deprived of the 13-residue N
      terminal peptide of Lom OMP and differing by the same tripeptide insertion. The
      PAA isoforms were observed in low amounts as compared to the other isoforms. In
      mature adults, only the two short isoforms were present. The complete sequence of
      PAA Scg OMP presents a large degree of sequence homology with Lom OMP (83%). The
      mixed Scg OMPs had the same biological effects as Lom OMPs. They induced
      precocious occurrence of both ecdysteroids and vitellogenin in the haemolymph and
      stimulated oocyte growth.

PMID- 9755476
TI  - A cuticular protein from the moulting stages of an insect.
AB  - A 22 kDa peptide was purified from prepupal cuticles of 5th instar Calpodes
      ethlius caterpillars. It was absent earlier in the stadium and from the egg and
      adult, i.e. it is related to cuticle turnover rather than cuticle structure. It
      was present at larval and metamorphic moults, showing that it is related to
      moulting not just metamorphosis. The cDNA corresponding to the 22 kDa peptide was
      isolated by antibody screening of an epidermal cDNA expression library.
      Hybridization to Calpodes genomic DNA showed that the gene was present as a
      single copy. The deduced amino acid sequence is not like any of the sequences of
      cuticular structural proteins that have been published, but has a 47 amino acid
      sequence similar to bacteriophage T7 N-acetylmuramoyl-L-alanine amidase (34%
      identical, 51% similar). The amino acid sequence, the timing of expression in
      development, and the similarity between the substrate of the bacteriophage
      amidase and components of insect cuticle, all suggest that the 22 kDa protein may
      have a role in cleaving chitin-peptide bonds as a prerequisite for digestion of
      the cuticle by chitinases and proteases.

PMID- 9755475
TI  - Molecular cloning and heterologous expression of a glutathione S-transferase
      involved in insecticide resistance from the diamondback moth, Plutella
      xylostella.
AB  - Four glutathione S-transferase (GST, EC 2.5.1.18) isozymes have been
      characterized in the larvae of the diamondback moth (DBM), Plutella xylostella
      L., a cosmopolitan insect pest of crucifiers. This work aimed at cloning and
      heterologously expressing the cDNA of DBM GST-3, an isozyme involved in this
      insect resistance to some organophosphorus insecticides, and studying the
      molecular basis for its increased expression in the resistant strains. Reverse
      transcription polymerase chain reaction (RT-PCR) using midgut mRNA from a methyl
      parathion resistant MPA strain and degenerate primers complimentary to the N
      terminal and internal amino acid sequences of GST-3 generated a 128 bp DNA
      product. A clone of 809 bp, obtained by screening a midgut cDNA library of MPA
      strain using this PCR product as probe, encoded a protein of 216 amino acids
      (calculated Mr 24,083 and pI 8.50). This GST of DBM, PxGST3, shared the highest
      (46.3%) amino acid sequence identity, among insects, to MsGST1 of Manduca sexta.
      PxGST3 mRNA level was considerably higher in MPA than in susceptible strains, and
      Southern blots suggested that gene amplification was probably not involved in the
      increased expression of this GST isozyme. Enzymatically active PxGST3 expressed
      heterologously in E. coli exhibited similar biochemical and toxicological
      properties as GST-3 purified from DBM larvae. It is the first cloned GST with a
      well-defined role in insecticide resistance.

PMID- 9755477
TI  - A hydrophobic peptide (VAP-peptide) of the silkworm, Bombyx mori: a unique role
      for adult activity proposed from gene expression and production at the terminal
      phase of metamorphosis.
AB  - A unique hydrophobic peptide (VAP-peptide) isolated from male adult heads of the
      silkworm, Bombyx mori, has been shown to act as a synergist to the diapause
      hormone when administered exogenously. Here, we investigated the true role of the
      endogenous VAP-peptide on differentiation and development of adult organs in the
      silkworm. By northern blot analyses, the VAP-peptide gene was shown to be
      exclusively expressed at the terminal phase of adult development in epithelial
      tissues, especially in the wing and the thoracic integument. In situ
      hybridization analysis revealed that the gene was highly expressed in the
      epidermal cells of the wing vein and the thoracic integument. The stage- and
      tissue-dependent gene expression were clearly correlated to the accumulation
      profile of VAP-peptide. In the adult thoracic integument, VAP-peptide was
      predominantly deposited in the cuticle layer. Affinity chromatography indicated
      the ability of VAP-peptide to bind to chitin. Based on its expression patterns,
      localization, and chemical properties, VAP-peptide is conceived to be a
      structural protein that participates in mechanical strengthening of specific
      cuticle structures, supporting their physical requirements in the adult life of
      the silkworm.

PMID- 9755478
TI  - Upregulation of a 23 kDa small heat shock protein transcript during pupal
      diapause in the flesh fly, Sarcophaga, crassipalpis.
AB  - A diapause upregulated cDNA clone was isolated from a cDNA library generated from
      brain mRNA of diapausing Sarcophaga crassipalpis pupae. The clone hybridized to a
      1600 bp transcript on a northern blot. The insert is 823 bp in length, has a
      tentative open reading frame of 615 bp, and codes for a 23 kDa protein. The clone
      has a high level of identity at the amino acid level with the four small heat
      shock proteins of Drosophila melanogaster. Northern analysis revealed no
      detectable expression of the transcript in diapause- or nondiapause-programmed
      wandering larvae, and only trace expression in nondiapausing pupae. But, the
      transcript was highly expressed beginning at the onset of diapause and continuing
      throughout diapause. Expression promptly decreased when diapause was terminated.
      In nondiapausing individuals the transcript was highly expressed in response to
      cold shock or heat shock, but temperature stress did not cause greater expression
      in diapausing pupae. The results imply that expression of this small heat shock
      protein, a response elicited by temperature stress in nondiapausing individuals,
      is a normal component of the diapause syndrome. The upregulation of this gene
      during diapause suggests that it plays an essential role during this
      overwintering developmental arrest.

PMID- 9755479
TI  - Basis for selective action of a synthetic molting hormone agonist, RH-5992 on
      lepidopteran insects.
AB  - The non-steroidal ecdysone agonist, RH-5992, induces a precocious incomplete molt
      in lepidopteran insects but is refractory to insects of other orders. We used two
      lepidopteran cell lines, FPMI-CF-203 (CF-203) and IPRI-MD-66 (MD-66) and two
      dipteran cell lines, DM-2 and Kc, to investigate the lepidopteran specificity of
      RH-5992. The mRNAs for hormone receptor 3 homologues cloned from Drosophila
      (DHR3) and Choristoneura (CHR3) are directly induced by 20-hydroxyecdysone (20E)
      and serve as suitable markers for studying ecdysone action. Dose response
      experiments showed that 10(-7) M 20E induced CHR3 mRNA in CF-203 cell and DHR3
      mRNA in DM-2 cells. Concentrations of RH-5992 as low as 10(-10) M induced CHR3
      mRNA in CF-203 cells, whereas concentrations as high as 10(-6) M induced only
      very low levels of DHR3 mRNA in DM-2 cells. Studies using 14C-RH-5992 revealed
      that lepidopteran cell lines (CF-203 and MD-66) retained more of this compound
      within the cells than the dipteran cell lines (DM-2 and Kc). The clearance of RH
      5992 from DM-2 cells was temperature dependent and was blocked by 10(-5) M
      ouabain, an inhibitor of Na+, K(+)-ATPase suggesting that the efflux was due to
      active transport.

PMID- 9755480
TI  - Osmoregulation and salinity effects on the expression and activity of Na+,K(+)
      ATPase in the gills of European sea bass, Dicentrarchus labrax (L.).
AB  - The European sea bass, Dicentrarchus labrax, tolerates salinities ranging from
      freshwater (FW) to hypersaline conditions. In two experiments, we analysed
      changes in plasma ions, muscle water content (MWC), gill Na+,K(+)-ATPase
      activity, and alpha-subunit mRNA expression during the course of acclimation from
      15 ppt salt water to FW or high salinity seawater (HSSW). In Experiment 1, fish
      (6.2 +/- 1.1 g) were acclimated from 15 ppt to either FW, 5, 15, 25, 50, or 60
      ppt SW and sampled after 10 days. Gill Na+,K(+)-ATPase activity was stimulated in
      FW- and in 50 and 60 ppt SW-groups relative to the 15 ppt control group. In
      Experiment 2, subgroups of fish (89 +/- 7 g) were transferred from 15 ppt SW to
      FW or 50 ppt SW, and sampled 1, 2, 4, and 10 days later. Plasma osmolality, [Na+]
      and [Cl-] decreased in the FW-group and increased in the HSSW-group one day after
      transfer and lasting until day 10. This was accompanied by a pronounced increase
      in MWC in the FW-group and an insignificant decrease in the HSSW-group. The
      plasma [Na+]:[Cl-]-ratio increased markedly in the FW-group and decreased
      slightly in the HSSW-group, suggesting acid-base balance disturbances after
      transfer. Gill Na+,K(+)-ATPase activity was unchanged in 15 ppt SW but doubled in
      FW- and HSSW-groups after transfer. In both groups, this was preceded by a 2- to
      5-fold elevation of the gill alpha-subunit Na+,K(+)-ATPase mRNA level. Thus
      increased expression of alpha-subunit mRNA is part of the molecular mechanism of
      both FW and SW acclimation in sea bass. Gill Na+,K(+)-ATPase Na(+)-, K(+)-, and
      ouabain-affinity were similar in fish acclimated to FW, 15 ppt, and HSSW,
      suggesting that identical isoforms of the catalytic subunit of the enzyme are
      expressed irrespective of salinity.

PMID- 9755481
TI  - Partial clone of the gene for AS protein of the lamprey Petromyzon marinus, a
      member of the albumin supergene family whose expression is restricted to the
      larval and metamorphic phases of the life cycle.
AB  - AS was previously found to be a liver-synthesized serum protein that is found in
      the larval (ammocoete), metamorphosing, and juvenile individuals during the life
      cycle of Petromyzon marinus but not in the sexually mature upstream-migrant
      individuals (Filosa et al. [1982] Comp. Biochem. Physiol., 72B:521-530; [1986]
      Comp. Biochem. Physiol., 83B:143-149; Ito et al. [1988] J. Exp. Zool., 245:256
      263). In the present work, a partial clone for the gene for the AS protein was
      isolated from a cDNA expression library made from ammocoete liver. Northern blots
      using this clone showed hybridization with mRNA from the intervals of the life
      cycle prior to the upstream-migration period but not from the upstream-migration
      period itself. The cloned DNA was sequenced and the deduced amino acid sequence
      was found to have 40% identity with an albumin (our SDS-1 protein) from the
      upstream migrants of P. marinus (Gray and Doolittle, [1992] Protein Sci., 1:289
      302), which is homologous to mammalian serum albumin. Thus the lamprey has two
      genes, AS and SDS-1, that code for different but similar albumin-like proteins,
      which predominate at different phases in its life cycle. It is suggested that AS
      protein, because it is present only at the earlier phases of the life cycle and
      because its gene is transcribed only during this same period, may be an early
      version of the alpha-fetoprotein (AFP) of mammals that is found only in the
      embryonic, fetal, and neonatal phase of their life cycle.

PMID- 9755482
TI  - Sulfur reduction by human erythrocytes.
AB  - Washed human erythrocytes incubated with glucose and S8 and purged with N2
      produced H2S at a nearly constant rate of 170 mumol (L cells)-1 min-1, which
      continued for several hours. In sealed vials up to 25 mM HS- accumulated. Glucose
      caused the fastest H2S production, although either lactate or glycerol could
      support slower rates. When glucose was added without S8, anoxic H2S production
      nonetheless occurred at about 1.5% of the maximum rate, after 24 hr totaling 0.5
      mmol H2S (L cells)-1, suggesting the presence of endogenous reducible sulfur.
      Anaerobic conditions were not required, since oxygenated cells produced H2S from
      S8 at 80% of the anoxic rate. Using cell lysates, production of H2S occurred
      after addition of either glutathione, NADH, or NADPH. The observations suggest
      possible physiological roles for H2S as an electron carrier, and are consistent
      with an evolutionary relationship between eukaryotic cytoplasm and sulfur
      reducing Archaea.

PMID- 9755483
TI  - Putative multiadhesive protein from the marine sponge Geodia cydonium: cloning of
      the cDNA encoding a fibronectin-, an SRCR-, and a complement control protein
      module.
AB  - Sponges (Porifera) representing the simplest metazoan phylum so far have been
      thought to possess no basal lamina tissue structures. One major extracellular
      matrix protein that is also a constitutive glycoprotein of the basal lamina is
      fibronectin. It was the aim of the present study to identify the native protein
      from the marine sponge Geodia cydonium and to isolate the corresponding cDNA. In
      crude extracts from this sponge protein(s) of M(r) of approximately 230 and
      approximately 210 kDa could be visualized by Western-blotting using an anti
      fibronectin [human] antibody. By PCR cloning from a cDNA library of G. cydonium
      we isolated a cDNA comprising one element of fibronectin, the type-III (FN3)
      module. The cDNA (2.3 kb long), encoding a 701 amino acid [aa] long putative
      "multiadhesive protein" termed MAP_GEOCY, was found to contain (i) a fibronectin
      , (ii) a scavenger receptor cysteine-rich [SRCR]-, and (iii) a short consensus
      repeat [SCR] module. The 89 aa long fibronectin module comprises the
      characteristic topology and conserved aa found in fibronectin type-III (FN3)
      elements. The SRCR module (101 aa) features the characteristics of group B SRCR
      molecules. The predominant proteins belonging to this group are the mammalian WC1
      , M130-, CD6- and CD5 antigens that probably are involved in immunological
      reactions. The SCR module (54 aa) shows the characteristics of type III SCR
      modules found in complement receptors. Phylogenetic analyses performed with all
      three building blocks of the "multiadhesive protein" showed that the respective
      sponge modules form independent, possibly basal, lineages in trees that include
      the corresponding modules from higher metazoan animals. In summary, these data
      demonstrate for the first time that the phylogenetically oldest Metazoa, the
      sponges, contain protein modules seen in higher animals in proteins of the
      extracellular matrix and in molecules involved in cell-mediated immune reactions
      in vertebrates.

PMID- 9755484
TI  - Acrosomal status of mouse spermatozoa in the oviductal isthmus.
AB  - The principal purpose of this study was to establish the acrosomal status of
      mouse spermatozoa stored in the isthmus of the oviduct after natural mating.
      Scanning electron microscopy of oviducts fixed about 6 hr before the estimated
      ovulation time showed numerous acrosome-intact spermatozoa attached to the
      mucosal surface of the oviduct, or trapped in the oviductal crypts. Nevertheless,
      an unambiguous assessment of the state of the acrosome requires transmission
      electron microscopy. Using this method, it was observed that the acrosome was
      intact in the 81% of spermatozoa attached to the mucosal surface but in only 31%
      of spermatozoa that were free in the lumen. Most of the free spermatozoa showed
      swelling or disruption of the acrosome. This result might indicate that the in
      vivo spermatozoon-oviductal mucosa interaction maintains the acrosome intact.
      Alternatively, it could mean that only ejaculated spermatozoa with a normal
      acrosome can establish such a mucosal relationship.

PMID- 9755485
TI  - Precursors of the purine backbone augment the inhibitory action of hypoxanthine
      and dibutyryl cAMP on mouse oocyte maturation.
AB  - In this study we have tested the hypothesis that precursors of the purine base
      backbone--glutamine, glycine, aspartic acid, and formate--promote meiotic arrest
      when included in medium containing established meiotic inhibitors and that this
      occurs in glucose-dependent fashion. An initial experiment established that in
      medium supplemented with 4 mM hypoxanthine and containing no purine precursors,
      very little meiotic arrest was maintained in cumulus cell-enclosed oocytes after
      17-18 hr (90% germinal vesicle breakdown; GVB). Increasing concentrations of
      glucose reduced the maturation percentage such that only 57% had matured at 0.55
      mM. The addition of 2 mM glutamine (Gln) alone reduced the maturation percentage
      in the absence of glucose (70% GVB), and the further addition of glucose revealed
      an additive inhibitory effect between these two supplements. Dose response
      experiments with Gln, glycine (Gly), aspartic acid and formate showed that in
      medium supplemented with hypoxanthine, very little inhibitory action was observed
      in the absence of glucose but that upon addition of this hexose, a dramatic
      decrease in maturation percentage was observed in the Gln and Gly groups. Results
      of experiments using combinations of precursors showed that when Gln and Gly were
      added together, greater augmentation of meiotic arrest maintained by either
      hypoxanthine or dibutyryl cAMP was achieved in the presence of glucose than with
      either amino acid alone. The addition of purine precursors significantly
      increased the extent of purine nucleotide production by oocyte-cumulus cell
      complexes, and this was accentuated by glucose. It is concluded that the presence
      of purine precursors can augment the meiosis-arresting action of established
      meiotic inhibitors in glucose-dependent fashion, and that this is due, at least
      in part, to their incorporation into purine nucleotides via the de novo synthetic
      pathway.

PMID- 9755486
TI  - Purification of the precursors to vitelline envelope proteins from serum of
      Sakhalin taimen, Hucho perryi.
AB  - High and low molecular weight vitelline envelope-related proteins (hVERP and
      lVERP) were purified from serum of vitellogenic female Sakhalin taimen (Hucho
      perryi) by a combination of ion-exchange, hydroxylapatite and gel filtration
      chromatography. The molecular weight of hVERP was estimated to be 83 kDa by gel
      filtration, and 48 kDa and 54 kDa in SDS-PAGE under non-reduced and reduced
      conditions, respectively. The molecular weight of lVERP was 56 kDa by gel
      filtration, and 42 kDa and 46 kDa on SDS-PAGE (non-reduced and reduced,
      respectively). Amino acid composition of hVERP was characterized by high content
      of proline (15.9%) and glutamic acid (13.8%). The lVERP had high contents of
      glutamic acid (10.8%) and aspartic acid (10.5%). Specific antibodies against
      hVERP and against lVERP were prepared by immunizing rabbits. The antiserum to
      hVERP stained bands corresponding to 98 kDa and 48 kDa of vitelline envelope (VE)
      in SDS-PAGE without reduction, whereas the antiserum to lVERP immunostained 98
      kDa and 42 kDa bands. Both specific antibodies recognized the vitelline envelope
      of vitellogenic oocytes immunocytochemically. Thus, hVERP and lVERP are
      precursors to vitelline envelope proteins in this species.

PMID- 9755487
TI  - Interaction of the copper(II) macrocyclic complexes with DNA studied by
      fluorescence quenching of ethidium.
AB  - The fluorescence quenching of DNA bound ethidium ion by copper(II) macrocyclic
      complexes has been investigated. The binding constant indicates that the stable
      assembly can be formed between the DNA and the metal complex. The replacement of
      the fluorophore by the metal complexes results in a decrease of the ethidium
      moles intercalating to the molar DNA base pair and the binding constant of the
      ethidium to the DNA. The quenching of the ethidium excited state by the Cu(II)
      complex follows linear Stern-Volmer behavior. The quenching constant decreases
      regularly with an increase of the ratio of the concentration of the bound
      ethidium to that of DNA base pair. The dependence of the quenching constant on
      the ratio can be used to estimate binding constants for the fluorescent molecule
      and metal complexes to DNA. This method does not depend strongly on the type and
      the extent of interaction of metal complexes with DNA, allowing for the
      determination of binding constants for metal complexes that exhibit small changes
      in absorption spectra upon binding. The precision of this method will ultimately
      be governed by outstanding agreement between the quenching constant measured and
      that calculated by using a correlation function of the ratio or the DNA bound
      concentration of ethidium with quenching constant.

PMID- 9755488
TI  - Bis(acetato)bis(1-methyl-4,5-diphenylimidazole)copper(II): preparation,
      characterization, crystal structure, DNA strand breakage and cytogenetic effect.
AB  - The preparation, characterization and antitumour properties of the complex
      [Cu(O2CMe)2L2] (1), where L = 1-methyl-4,5-diphenylimidazole, are described. The
      crystal structure of 1 (triclinic, space group P1, a = 6.743(1), b = 8.006(1), c
      = 15.898(1) A, alpha = 102.87(1), beta = 101.10(1), gamma = 76.76(1) degree, Z =
      1) has been determined (R = 0.0254, Rw = 0.0275). In the centrosymmetric complex
      the copper ion is in an essentially square planar environment consisting of two
      pyridine-type imidazole nitrogen atoms and an oxygen atom from each acetate
      ligand; the second oxygen atoms of the carboxylate functionalities are involved
      in weak interactions with the metal completing the coordination to a very
      distorted tetragonal bipyramid. Complex 1 has been also characterized by
      elemental analyses, thermal methods, variable-temperature magnetic susceptibility
      and spectroscopic (IR and far-IR, FT-Raman, UV/VIS, EPR) techniques. The effect
      of the complex on the in vitro DNA strand breakage was examined. It was found
      that 1 causes degradation on the linearized pKS DNA, ds and ss DNA. High
      concentrations of this Cu(II) complex cause scissions on the relaxed and the
      supercoiled DNA. Furthermore, the in vivo cytogenic effect of 1 was examined on
      human lymphocyte cells. This study presents indications that 1 could have some
      relevance in the treatment of tumour cell lines. An orbital interpretation of the
      interaction of 1 with the DNA bases is proposed.

PMID- 9755489
TI  - Synthesis, characterization, and antitumor activity of new platinum(IV) trans
      carboxylate complexes: crystal structure of [Pt(cis-1,4-DACH)trans
      (acetate)2Cl2].
AB  - A series of novel platinum(IV) cisplatin analogues of the type [Pt(cis-1,4
      DACH)trans-(L)2Cl2] (where cis-1,4-DACH = cis-1,4-diaminocyclohexane and L =
      acetate, propionate, butyrate, valerate, hexanoate, heptanoate, octanoate,
      nonanoate, or decanoate) was synthesized and characterized by elemental analysis,
      IR, 13C-NMR, and 195Pt-NMR spectroscopy. The structure of [Pt(cis-1,4-DACH)trans
      (acetate)2Cl2] (1) was determined by X-ray crystallography. The crystals were
      monoclinic, space group P2(1)/n (no. 14) with a = 10.193(2), b = 10.687(2), c =
      14.265(3) A, beta = 99.67(3) degrees, Z = 4. The total reflections collected were
      2556. The structure refinement converged to R1 = 0.0539 and wR2 = 0.1531. In this
      complex, platinum has distorted octahedral geometry, and cis-1,4-DACH is in a
      unique twist-boat configuration. cis-1,4-DACH forms a seven-member chelating ring
      with platinum, leading to considerable strain in bidentate DACH binding. The
      strain is evidenced by a large 126.5(9) degrees C-N-Pt angle. The N-Pt-N angle is
      expanded to 97.4(5) degrees owing to geometric constraints of the cis-1,4-DACH
      geometry. Three lower homologs of the cis-1,4-DACH-Pt(IV) series were tested in
      the murine L1210/0 leukemia model for antitumor activity. The results indicate
      that activity decreases in ascending the homologous series, and that the activity
      of two of the complexes is substantially better than that of cisplatin with
      respect to increase in life span and cures.

PMID- 9755490
TI  - Stabilization of the T-state of ferrous human adult and fetal hemoglobin by
      Ln(III) complexes: a thermodynamic study.
AB  - The effect of the lanthanide(III) complexes [Gd(1,4,7,10-tetraazacyclododecane
      N,N',N", N"'-tetrakis(methylenephosphonate))]5- (Gd-DOTP) and La-DOTP on the
      oxygen binding and spectroscopic properties of human adult and fetal hemoglobin
      (HbA and HbF, respectively) has been investigated. The affinity of Gd-DOTP and La
      DOTP for oxygenated HbA (HbAO2; KHbAO2 = 2.6 x 10(-3) M) is closely similar to
      that observed for Ln(III) complexes association to nitrosylated HbA (HbANO KHbANO
      = 1.8 x 10(-3) M) and to aquo-met HbA (met-HbA; Kmet-HbA = 1.9 x 10(-3) M), being
      lower than that determined for Gd-DOTP and La-DOTP binding to the deoxygenated
      form of the tetramer (HbAd; KHbAd = 3.0 x 10(-4) M). The affinity of Gd-DOTP for
      deoxygenated HbF (HbFd; KHbFd = 9.5 x 10(-4) M) and oxygenated HbF (HbFO2; KHbFO2
      = 3.7 x 10(-3) M) is lower than that observed for Ln(III) complexes association
      to HbAd and HbAO2, respectively. Gd-DOTP and La-DOTP bind to HbA and HbF with a
      1:1 stoichiometry per tetramer. Increasing Gd-DOTP and La-DOTP concentration,
      oxygen affinity for HbA decreases (i.e. P50 increases), this effect being minor
      for HbF. Upon binding of Ln(III) complexes to HbANO, the X-band EPR spectrum and
      the absorption spectrum in the Soret region display the characteristics which
      have been attributed to the T-state of the ligated tetramer. These results
      represent a clear cut evidence for the specific binding of Gd-DOTP and La-DOTP to
      the 2,3-D-glycerate bisphosphate (BPG) pocket (i.e. at the dyad axis, in between
      the beta-chains) of HbA and HbF. The effect of Ln(III) complexes on the ligand
      binding and spectroscopic properties of HbA and HbF is reminiscent that of BPG,
      the physiological modulator of human Hb action.

PMID- 9755491
TI  - Solution studies of the antitumor complex dichloro 1,2
      propylendiaminetetraacetate ruthenium (III) and of its interactions with
      proteins.
AB  - A mixed complex of ruthenium (III) with 1,2-propylendiaminetetraacetate (PDTA)
      and chloride--RAP hereafter--has been found to exhibit favorable anticancer
      properties in vivo. To get some insight into the possible mechanism of action of
      this ruthenium (III) complex, its solution behavior and reactivity with proteins
      were investigated through absorption, circular dichroism and 1H NMR
      spectroscopies. Under physiological conditions RAP slowly looses the two
      coordinated chlorine atoms to produce a number of ruthenium (III) reactive
      species; a description of the distribution of these species on the dependence of
      pH has been obtained through 1H NMR studies of the hyperfine shifted signals.
      Remarkably, through the different solution conditions employed in this study, the
      ruthenium ion always remains in the 3+ oxidation state and the PDTA ligand is
      always bound to the metal. Upon reaction with albumin, apotransferrin or diferric
      transferrin, at a 1:1 ratio, RAP rapidly binds to these proteins to produce
      substantially equivalent and relatively stable adducts. This behavior is
      tentatively interpreted in terms of a tight interaction between RAP and surface
      residues of these proteins. The implications of these findings for the biological
      action of this novel ruthenium (III) compound are discussed.

PMID- 9755492
TI  - Antibacterial tests of bismuth(III)-quinolone (ciprofloxacin, cf) compounds
      against Helicobacter pylori and some other bacteria. Crystal structure of
      (cfH2)2[Bi2Cl10].4H2O.
AB  - The antibacterial tests of two bismuth(III)-ciprofloxacin (cf) compounds against
      Helicobacter pylori (H. pylori) and some other bacteria were performed. The
      results have shown that the activity of both compounds is comparable to that of
      ciprofloxacin hydrochloride. The crystal structure of (cfH2)2[Bi2Cl10].4H2O (cfH2
      = doubly protonated molecule of cf) is presented and discussed. The compound was
      isolated from acidic medium where quinolone is protonated and thus no bonding
      between quinolone and bismuth was observed. The bismuth(III) ions are coordinated
      by chloride ions forming dinuclear [Bi2Cl10]4- anions. The charge of this ion is
      compensated with protonated quinolone molecules (ionic interactions).

PMID- 9755493
TI  - The bidirectional effect of vanadyl ion on the oxygen affinity of human
      hemoglobin.
AB  - The bidirectional effects of vanadyl on the oxygen affinity of hemoglobin depend
      on the mole ratio of vanadyl to Hb(R). In low R, the vanadyl ion increases Hb's
      oxygen affinity due to DPG hydrolysis. The lowered oxygen affinity in higher R is
      mainly due to the reactive-oxygen-species, probably superoxide, induced oxidation
      of Fe(II)-Hb to Fe(III)-Hb. The conformation change due to vanadyl binding
      contribute also to the lowered oxygen binding, but is monotonously decreasing
      with increasing of R values.

PMID- 9755494
TI  - Complexation of type 2 copper by cytochrome c oxidase: probing of metal-specific
      binding sites by electron paramagnetic resonance.
AB  - Cytochrome c oxidase, CcO, contains at least four, probably five type 2 copper
      binding sites per monomer in addition to the mixed valence [CuA(1.5+)CuA(1.5+)],
      S = 1/2 center and the EPR-silent CuB. Electron paramagnetic resonance (EPR)
      parameters for these site are g parallel = 2.22 and A parallel = 195 G. Nitrogen
      superhyperfine structure is observed in the g perpendicular region, with A
      perpendicular N of around 15 G. The EPR parameters for Cu(2+) bound to a
      synthetic peptide, AHGSVVKSEDYALPS, are similar to the parameters for the type 2
      sites in CcO. The lines in the EPR spectrum of the type 2 site in the synthetic
      peptide are better resolved at low microwave frequency (3.4 GHz). Resolved lines
      in the expansion of the MI = -1/2 line in the g parallel region of the low
      frequency spectrum are attributed to superhyperfine structure from three almost
      equivalent nitrogen donor atoms bound to Cu(2+) in a square planar configuration.
      The MI = -1/2 line in the g parallel region for excess Cu(2+) bound to CcO is not
      as well resolved as for the synthetic peptide, presumably because the four or
      five binding sites per monomer are similar, but not exactly equivalent. These
      binding sites are proposed to be at the N-terminus of subunits of CcO, for
      example, at subunit IV where the sequence is AHGS-. Nitrogen donor atoms from the
      alpha-amino group of the amino terminal residue, the imidazole group of
      histidine, and a peptide nitrogen are predicted to comprise the binding site.

PMID- 9755495
TI  - A quantitative method for analysing AFM images of the outer surfaces of human
      hair.
AB  - Cuticle step height is an important parameter for the quantitative assessment of
      human hair. This paper describes a novel, computational method for the rapid
      calculation of step heights from atomic force microscope images obtained from
      large numbers of specimens. Such an approach is necessary to allow a statistical
      analysis of the inherently wide distribution of cuticle step heights
      characteristic of a single hair sample. The method described will be of use to
      cosmetic formulation chemists and forensic scientists and also to dermatologists
      in the field of disease diagnosis.

PMID- 9755496
TI  - Neurofilament-L homopolymers are less mechanically stable than native
      neurofilaments.
AB  - Neurofilaments are cytoskeletal components of neurones that are thought to play
      an important structural role in the axon. Specific functions of neurofilaments
      are not yet well defined; however, other intermediate filaments are known to have
      structural and mechanical functions in different cell types. The atomic force
      microscope (AFM) can be used to visualize and manipulate biological structures
      through direct physical contact. This allows the AFM to be used to probe the
      mechanical properties of these structures. In this paper we present AFM images of
      native neurofilaments isolated from bovine spinal cord, composed of NF-L, NF-M
      and NF-H, and filaments polymerized in vitro from purified NF-L. Morphologically
      these structures, in solution and under ambient conditions, are in agreement with
      previous data from electron microscopy. However, repeated scanning of NF-L
      homopolymers (in solution) produced significant disruptions of segments of
      filaments, both within and at the ends of the filaments. This disruption resulted
      in complete loss of portions of the filaments and in breaks in the continuity of
      the filaments. Repeated scanning of isolated native neurofilaments under similar
      conditions produced no detectable structural changes. Under extremely high
      applied forces the native neurofilaments were bent and distorted by the action of
      the AFM tip, but were never broken. These data suggest that purified NF-L is not
      sufficient to confer complete mechanical stability to neurofilaments.

PMID- 9755497
TI  - Star length distribution: a volume-based concept for the characterization of
      structural anisotropy.
AB  - Determination and quantification of anisotropy is of great interest in research
      fields dealing with physical structures or surface textures. In this paper, a
      volume-based method is presented, which essentially determines the mean object
      length in a certain direction for a typical point within a structure or texture.
      The mean object lengths for all orientations together form the so-called star
      length distribution (SLD). The validity and the accuracy of the SLD method are
      investigated, and illustrated by applying it to trabecular bone. By using a line
      sampling algorithm, the relation with other anisotropy measures could be studied
      analytically. Preliminary tests suggest that with SLD a more exact description of
      the mechanical properties of porous structures may be obtained than with other
      anisotropy measures. However, due to possible secondary orientations that become
      apparent with SLD, a fabric tensor must be of rank higher than two in order to
      properly describe an orthogonal structure mathematically.

PMID- 9755498
TI  - X-ray microanalysis of native airway surface liquid collected by cryotechnique.
AB  - The airway surface liquid (ASL) that lines the surface epithelium of the
      tracheobronchial tree is of vital importance to the airway defence against
      microbial invasion and damage due to environmental factors. Little is known about
      the ASL collected in situ in native conditions, owing to difficulties in
      collecting ASL without causing damage to the airway mucosa. We have developed a
      method to collect and analyse the elemental composition of tracheal ASL in
      pathogen-free mice. A specially designed cryoprobe, adapted to the internal
      curvature of the mouse trachea, was used to collect the native ASL from the
      tracheal surface. The complete ASL elemental composition including [Na] = 5.5 +/-
      0.3, [Cl] = 1.3 +/- 0.3, [K] = 1.1 +/- 0.2, [Ca] = 1.2 +/- 0.3, [P] = 1.5 +/-
      0.8, [S] = 1.7 +/- 0.4 and [Mg] = 1.3 +/- 0.4 mmol L-1 was determined by X-ray
      micro-analysis. We demonstrate here that the technique that we used for ASL
      collection maintained perfectly the airway epithelial integrity and
      functionality.

PMID- 9755499
TI  - Cryo-TEM liquid nitrogen splash guard.

PMID- 9755500
TI  - Determination of calcium binding sites in gas-phase small peptides by tandem mass
      spectrometry.
AB  - Low-energy (LE) and high-energy (HE) collisionally activated decompositions (CAD)
      of calcium/peptide complexes of the form [M - H + Ca]+ and [M + Ca]2+ reflect the
      site of calcium binding in various gas-phase peptides that are models of the
      calcium binding site III of rabbit skeletal troponin C. The Ca2+ binding sites
      involve an aspartic acid, glutamic acid, and asparagine, which are in the metal
      binding loops of calcium-binding proteins. Both fast atom bombardment (FAB) and
      electrospray ionization (ESI) were used to generate the metal/peptide complexes.
      When submitted to LE CAD, ESI-produced Ca2+/peptide complexes undergo
      fragmentations that are controlled by Ca2+ binding and provide information on the
      Ca2+ binding site. The LE CAD spectra are simple, indicating that Ca2+ binding
      involves specific oxygen ligands including acidic side chains and that only a few
      low-energy fragmentation channels exist. The HE CAD spectra of FAB-produced
      Ca2+/peptide complexes are more complex, owing to the introduction of high
      internal energy into the precursor ion. Interactions of the other alkaline-earth
      metal ions Mg2+ and Ba2+ with these peptides reveal that the ligand preferences
      of these metal ions are slightly different than those of Ca2+.

PMID- 9755501
TI  - Analysis of peptides, proteins, protein digests, and whole human blood by
      capillary electrophoresis/electrospray ionization-mass spectrometry using an in
      capillary electrode sheathless interface.
AB  - An in-capillary electrode sheathless interface was applied to the capillary
      electrophoresis/electrospray ionization-mass spectrometry (CE/ESI-MS) analysis of
      mixtures of small peptides, proteins, and tryptic digests of proteins. The
      effects of different experimental parameters on the performance of this CE/ESI-MS
      interface were studied. The distance of the in-capillary electrode from the CE
      outlet and the length of the electrode inside the capillary had no significant
      effects on the CE separation and ESI behavior under the experimental conditions
      used. However, significant enhancement of the sensitivity resulted from the use
      of narrower CE capillaries. Using a quadrupole mass spectrometer, an
      aminopropylsilane-coated capillary, and a wide scan mass-to-charge ratio range of
      500-1400, detection limits of approximately 4, 1, and 0.6 fmol for cytochrome c
      and myoglobin were achieved for 75-, 50-, and 30-micron inner diameter
      capillaries, respectively. Approximately one order of magnitude lower detection
      limits were achieved under the multiple-ion monitoring mode. The application of
      the in-capillary electrode sheathless interface to real-world samples was
      demonstrated by CE/ESI-MS analysis of a human blood sample.

PMID- 9755502
TI  - Antimicrobial susceptibilities of strains of Nocardia brasiliensis isolated from
      soil of Tucuman.
AB  - The activity of antimicrobial agents against soil isolates of N. brasiliensis was
      studied by determination of the minimum inhibitory concentrations (MICs) and disk
      diffusion technique, according to the National Committee for Clinical Laboratory
      Standards (NCCLS). The objectives were: (a) to study the patterns of sensitivity
      among regional strains of N. brasiliensis isolated from natural sources (soil) of
      different zones of Tucuman province; (b) to correlate these results with those
      previously obtained with regional strains of N. brasiliensis isolated from human
      mycetomas, as a contribution in the evaluation of the importance of the natural
      reservoir area of the potentially pathogen strains. The results obtained by both
      methods identified strains of N. brasiliensis from soils with similar patterns of
      susceptibility to the strains N. brasiliensis isolated from human mycetomas. This
      showed strains sensitive and resistant to antibiotics. The majority of the
      isolates of N. brasiliensis from soils showed higher susceptibilities to
      antibiotics than the strains isolated from human mycetomas. Among the antibiotics
      studied, cefotaxime, ceftriaxone and gentamicin were the most effective against
      all the regional strains tested, and these results are correlated with those
      obtained with regional strains that cause human mycetomas.

PMID- 9755503
TI  - Cutaneous Pythiosis insidiosi in calves from the Pantanal region of Brazil.
AB  - Two cases of cutaneous Pythiosis insidiosi were diagnosed in cattle from the
      Pantanal region, Brazil. The lesions were observed in the limbs of two 8-month
      old beef calves. Close examination showed local swelling and focal ulceration of
      the skin. Microscopically, there was multifocal granulomatous dermatitis with
      intralesional Pythium insidivosum hyphae. The diagnosis was based on the
      morphological aspects, immunohistochemical findings and culture of the etiologic
      agent.

PMID- 9755504
TI  - Isolation of a petite mutant from a histidine auxotroph of Candida albicans and
      its characterization.
AB  - Respiration-deficient (petite) mutations have been induced in various yeasts,
      which are categorized as petite-positive. Candida albicans was classified among
      the petite-negative yeasts. Since then, a few reports have appeared, describing
      the isolation of petite mutants in C. albicans. We report in the present study on
      the isolation of a petite mutant of C. albicans-SAR1. This mutant was isolated
      from a histidine auxotroph of C. albicans after mutagenesis with N-methyl-N'
      nitro-N-nitrosoguanidine, thus our petite mutant carries a double mutation. SAR1
      was characterized morphologically, biochemically and ultrastructurally. The
      results revealed differences from the wild type in respect to morphological,
      physiological and biochemical characteristics. Electron microscopy showed that
      the cells of the petite mutant contain only very few mitochondria that looked
      'thread like' without any cristae. The significance of the mutation in the
      virulence of the mutant vs. that of the wild-type is being assessed.

PMID- 9755505
TI  - Monoclonal antibodies directed against extracellular matrix proteins reduce the
      adherence of Candida albicans to HEp-2 cells.
AB  - The presence of the extracellular matrix (ECM) proteins collagen types I and IV,
      laminin and fibronectin on the surface of HEp-2 cells was confirmed by flow
      cytometry using monoclonal antibodies. Monoclonal antibodies directed against
      these ECM proteins reduced the adherence of C. albicans ATCC 44990 to HEp-2
      cells, the greatest reductions being evident in assays which incorporated anti
      collagen type IV monoclonal antibody. The ability of sugaramines to inhibit the
      adherence of C. albicans to a variety of cell types has been demonstrated
      previously and the most significant reduction in C. albicans-HEp-2 adherence was
      in assays which incorporated 0.2M galactosamine. The combination of anti-collagen
      IV monoclonal antibody and galactosamine reduced the adherence of C. albicans to
      HEp-2 cells by approximately 70% (p < 0.05).

PMID- 9755506
TI  - Experimental penetration of Trichophyton mentagrophytes into human stratum
      corneum.
AB  - We present confirmation of the experimental penetration of Trichophyton
      mentagrophytes into human stratum corneum under designated conditions of
      temperature and humidity. When stratum corneum, obtained from healthy human heel
      region, was incubated at 100% humidity, mycelium was observed in the corneum
      layer on day 2 at 35 degrees C and 27 degrees C, and on day 4 at 15 degrees C. At
      90% humidity, the hyphae penetrated into the stratum corneum on day 4 at 35
      degrees C, and on day 6 at 27 degrees C. Whereas, at 80% humidity, no fungal
      elements were observed in the stratum corneum at both 27 degrees C and 35 degrees
      C for up to 7 days. These data suggested that humidity was a more important
      environmental factor for penetration than temperature, and that at least 90%
      humidity is necessary for dermatophytes to penetrate into the stratum corneum
      within a few days. Mean humidity in the interdigital space between the fourth and
      fifth toes was found to be approximately 98%.

PMID- 9755507
TI  - Comparing properties of brains and computers.
AB  - The criterion that pure natural science can only investigate objective phenomena
      which can be observed by independent observers sets certain limits to pure
      natural scientific understanding of brain functions. It excludes consciousness
      and feelings since these are only subjectively accessible and alternatives cannot
      be decided objectively. The limitations of brain research are discussed by
      comparing the properties of brains and computers. At least for the time being we
      do not know of any natural scientific--i.e. physical or chemical--method which
      allows the objective measurement of consciousness, sensations, and emotions. In
      addition it is discussed how and in how far our brain understands its surrounding
      nature.

PMID- 9755508
TI  - Representation in natural and artificial agents: an embodied cognitive science
      perspective.
AB  - The goal of the present paper is to provide an embodied cognitive science view on
      representation. Using the fundamental task of category learning, we will
      demonstrate that this perspective enables us to shed new light on many pertinent
      issues and opens up new prospects for investigation. The main focus of this paper
      is on the prerequisites to acquire representations of objects in the real world.
      We suggest that the main prerequisite is embodiment which allows an agent--human,
      animal or robot--to manipulate its sensory input such that invariances are
      generated. These invariances, in turn, are the basis of representation formation.
      In other words, the paper does not focus on representations per se, but rather
      discusses the various processes involved in order to make learning and
      representation acquisition possible. The argument structure is as follows. First
      we introduce two new perspectives on representation, namely frame-of-reference,
      and complete agent. Then we elaborate the complete agent perspective and focus in
      particular on embodiment and situatedness. We argue that embodiment has two main
      aspects, a dynamic and an information theoretic one. Focusing on the latter,
      there are a number of implications: Representation can only be understood if the
      embedding of the neural substrate in the physical agent is known, which includes
      morphology (shape), positioning and nature of sensors. Because an autonomous
      mobile agent in the real world is exposed to a continuously changing high
      dimensional stream of sensory stimulation, if it is to learn category
      distinctions, it first needs a focus of attention mechanism, and then it must
      have a way to reduce the dimensionality of this high-dimensional sensory stream.
      Learning is very hard because the invariances are typically not found in the
      sensory data directly--the classical problem of object constancy: it is a so
      called type 2 problem. Rather than trying to improve the learning algorithms-
      which is the standard approach--the embodied cognitive science view suggests a
      different approach which focuses on the nature of the data: the agent is not
      passively exposed to a given data distribution, but, by exploiting its body and
      through the interaction with the environment, it can actually generate the data.
      More specifically, it can generate correlated data that has the property that it
      can be easily learned. This learnability is due to redundancies resulting from
      the appropriate interactions with the environment. Through such interactions, the
      former type 2 problem is transformed into a type 1 problem, thus reducing the
      complexity of the learning task by orders of magnitude. By observing the frame-of
      reference problem we will discuss to what extent these invariances are reflected-
      represented--in the "neural substrate", i.e. the internal mechanisms of the
      agent. It is concluded, that representation is not a concept that can be studied
      in the abstract, but should be elaborated in the context of concrete agent
      environment interactions. These ideas are all illustrated with examples of
      natural agents and artificial agents. In particular, we will present a suite of
      experiments on simulated and real-world artificial agents instantiating the main
      arguments.

PMID- 9755509
TI  - The representation of space and the hippocampus in rats, robots and humans.
AB  - Experimental evidence suggests that the hippocampus represents locations within
      an allocentric representation of space. The environmental inputs that underlie
      the rat's representation of its own location within an environment (in the firing
      of place cells) are the distances to walls, and different walls are identified by
      their allocentric direction from the rat. We propose that the locations of goals
      in an environment is stored downstream of the place cells, in the subiculum. In
      addition to firing rate coding, place cells may use phase coding relative to the
      theta rhythm of the EEG. In some circumstances path integration may be used, in
      addition to environmental information, as an input to the hippocampal system. A
      detailed computational model of the hippocampus successfully guides the
      navigation of a mobile robot. The model's behaviour is compared to
      electrophysiological and behavioural data in rats, and implications for the role
      of the hippocampus in primates are explored.

PMID- 9755510
TI  - Modular organization of motor behavior.
AB  - The issue of translating the planning of arm movements into muscle forces is
      discussed in relation to the recent discovery of structures in the spinal cord.
      These structures contain circuitry that, when activated, produce precisely
      balanced contractions in groups of muscles. These synergistic contractions
      generate forces that direct the limb toward an equilibrium point in space.
      Remarkably, the force outputs, produced by activating different spinal-cord
      structures, sum vectorially. This vectorial combination of motor outputs might be
      a mechanism for producing a vast repertoire of motor behaviors in a simple
      manner.

PMID- 9755511
TI  - Visual recognition based on temporal cortex cells: viewer-centred processing of
      pattern configuration.
AB  - A model of recognition is described based on cell properties in the ventral
      cortical stream of visual processing in the primate brain. At a critical
      intermediate stage in this system, 'Elaborate' feature sensitive cells respond
      selectively to visual features in a way that depends on size (+/- 1 octave),
      orientation (+/- 45 degrees) but does not depend on position within central
      vision (+/- 5 degrees). These features are simple conjunctions of 2-D elements
      (e.g. a horizontal dark area above a dark smoothly convex area). They can arise
      either as elements of an object's surface pattern or as a 3-D component bounded
      by an object's external contour. By requiring a combination of several such
      features without regard to their position within the central region of the visual
      image, 'Pattern' sensitive cells at higher levels can exhibit selectivity for
      complex configurations that typify objects seen under particular viewing
      conditions. Given that input features to such Pattern sensitive cells are
      specified in approximate size and orientation, initial cellular 'representations'
      of the visual appearance of object type (or object example) are also selective
      for orientation and size. At this level, sensitivity to object view (+/- 60
      degrees) arises because visual features disappear as objects are rotated in
      perspective. Processing is thus viewer-centred and the neurones only respond to
      objects seen from particular viewing conditions or 'object instances'. Combined
      sensitivity to multiple features (conjunctions of elements) independent of their
      position, establishes selectivity for the configurations of object parts (from
      one view) because rearranged configurations of the same parts yield images
      lacking some of the 2-D visual features present in the normal configuration.
      Different neural populations appear to be selectively tuned to particular
      components of the same biological object (e.g. face, eyes, hands, legs), perhaps
      because the independent articulation of these components gives rise to correlated
      activity in different sets of input visual features. Generalisation over viewing
      conditions for a given object can be established by hierarchically pooling
      outputs of view-condition specific cells with pooling operations dependent on the
      continuity in experience across viewing conditions. Different object parts are
      seen together and different views are seen in succession when the observer walks
      around the object. The view specific coding that characterises the selectivity of
      cells in the temporal lobe can be seen as a natural consequence of selective
      experience of objects from particular vantage points. View specific coding for
      the face and body also has great utility in understanding complex social signals,
      a property that may not be feasible with object-centred processing.

PMID- 9755512
TI  - An architecture for distributed visual memory.
AB  - The development of autonomous as well as situated robots is one of the great
      remaining challenges and involves a number of different scientific disciplines.
      In spite of recent dramatic progress, it remains worthwhile to examine natural
      systems, because their abilities are still out of reach. Motivated by research
      work done in the fields of cognitive systems, visual perception, and psychology
      of memory we designed and implemented a memory architecture for visual tasks.
      Structural and functional concepts of the memory architecture were modeled on the
      ones found in natural systems. We present an efficient implementation based on
      parallel programming techniques. The memory module is integrated into a
      distributed system for speech and image analysis, which is currently developed in
      the Sonderforschungsbereich (SFB) 360, Situated Artificial Communicators, where a
      hybrid vision system combining neural and semantic networks is used.

PMID- 9755513
TI  - How can adaptive behavioural plasticity be implemented in the mammalian brain?
AB  - The adaptive control of behaviour requires brain mechanisms for the selection
      (i.e. activation and suppression) of responses, as well as mechanisms for the
      modulation of the response vigour. The concept of motivation postulates the
      existence of brain centres that regulate the selection and strength of
      behavioural responses. The present paper provides examples from the behavioural
      neurosciences for brain mechanisms that lead to adaptive changes of an organisms
      responsiveness to external stimuli. The mammalian startle response is a simple
      defensive behaviour which is mediated by an oligosynaptic pathway located in the
      lower brainstem. The startle response is enhanced by aversive states (fear,
      anxiety) and attenuated by appetitive states (pleasure), which can be regarded as
      an example of motivational priming. Furthermore, the startle response is
      inhibited by a weak sensory stimulus presented shortly before the startling
      stimulus. The suppression of startle by a prepulse is an example of sensorimotor
      gating, a principle that is important for the hierarchical organisation of
      behaviour. This paper describes the neuronal mechanisms underlying the modulation
      (prepulse inhibition and fear potentiation) of the startle response in rats, and
      discusses the possible adaptive significance of these different phenomena of
      behavioural plasticity.

PMID- 9755515
TI  - Motion segmentation in artificial and biological system.
AB  - In the early steps of visual information processing motion is one of the most
      important queues for the development of spatial representations. Obstacle
      detection and egomotion estimation are only two examples of the powerfulness of
      visual motion detection systems. The underlying process of information extraction
      has to be active due to the observer's capabilities of egomotion. This means that
      the observer's motion has an impact on the projected retinal motion field.
      Therefore one of the challenging tasks for biological as well as for technical
      vision systems is to couple retinal motion and egomotion and to uncouple
      egomotion and object motion. The following sections describe a model that couples
      visual motion processing with the egomotion parameters of a moving observer.
      Beneath a theoretical introduction of the model an application to traffic scene
      analysis is presented. At last the paper relates the model to biological motion
      processing systems.

PMID- 9755514
TI  - How it is to be the brain of a monkey.
AB  - Hypotheses are presented on neural peculiarities of the monkey brain that
      distinguish monkeys from other mammals and man: The unique feature of cortical
      tissue is that it can be applied serially. It fulfils some requirements of a
      powerful visual system. The richness of visual as compared to other signals has
      yielded a basis for recognizing the bodily similarity of oneself to conspecifics.
      A visuo/motor coupling trained on oneself but applied to conspecifics ("aping")
      evolved. Long series of (generalized visuo/visual) computations feasible in a
      very large cortex would produce excessive delays that would not correspond to
      outer world delays. The new human solution to this is an "offline" system in
      which temporal relationships are described by excitation patterns. This gives
      rise to a rapid expansion of the cortex. In humans, a "meaning" has to be
      attributed to the mutual (computational) relationships of excitation patterns in
      the offline system, by a reference to the corresponding relationships that would
      be valid in the normal (online) system. "Perception" is a corollary of this. The
      offline treatment of time, together with "aping", leads to new types of helping
      and other social interactions. Monkeys may be compared to humans not using their
      offline system in the state of "absent-mindedness". Experimental approaches
      departing from excitation patterns are discussed.

PMID- 9755517
TI  - Emergence of spatio-temporal patterns in neuronal activity.
AB  - This paper explores if dynamic modulation of coherent firing serves cortical
      functions. We recorded neuronal activity in the frontal cortex of behaving
      monkeys and found that temporal coincidences of spikes firing of different
      neurons can emerge within a fraction of a second in relation to the animal
      behavior. The temporal patterns of the correlation could not be predicted from
      the modulations of the neurons firing rate and finally, the patterns of
      correlation depend on the distance between neurons. These findings call for a
      revision of prevailing models of neural coding that solely rely on firing rates.
      The findings suggest that modification of neuronal interactions can serve as a
      mechanism by which neurons associate rapidly into a functional group in order to
      perform a specific computational task. Increased correlation between members of
      the groups, and decreased or negative correlation with others, enhance the
      ability to dissociate one group from concurrently activated competing groups.
      Such modulation of neuronal interactions allows each neuron to become a member of
      several different groups and participate in different computational tasks.

PMID- 9755518
TI  - Cellular dynamics of network memory.
AB  - One example of "emergence" is the development, as a result of neural ontogeny and
      living experience, of cortical networks capable of representing and retaining
      cognitive information. A large body of evidence from neuropsychology,
      electrophysiology and neuroimaging indicates that so-called working memory and
      long-term memory share the same neural substrate in the cerebral cortex. That
      substrate consists in a system of widespread, overlapping and hierarchically
      organized networks of cortical neurons. In this system, any neuron or group of
      neurons can be part of many networks, and thus many memories. Working memory is
      the temporary activation of one such network of long-term memory for the purpose
      of executing an action in the near future. The activation of the network may be
      brought about by stimuli that by virtue of prior experience are in some manner
      associated with the cognitive content of the network, including the response of
      the organism to those stimuli. The mechanisms by which the network stays
      activated are presumed to include the recurrent re-entry of impulses through
      associated neuronal assemblies of the network. Consistent with this notion is the
      following evidence: (1) working memory depends on the functional integrity of
      cortico-cortical connective loops; and (2) during working memory, remarkable
      similarities--including "attractor behavior"--have been observed between firing
      patterns in real cortex and in an artificial recurrent network.

PMID- 9755516
TI  - Simulation of complex movements using artificial neural networks.
AB  - A simulated network for controlling a six-legged, insect-like walking system is
      proposed. The network contains internal recurrent connections, but important
      recurrent connections utilize the loop through the environment. This approach
      leads to a subnet for controlling the three joints of a leg during its swing
      which is arguably the simplest possible solution. The task for the stance subnet
      appears more difficult because the movements of a larger and varying number of
      joints (9-18: three for each leg in stance) have to be controlled such that each
      leg contributes efficiently to support and propulsion and legs do not work at
      cross purposes. Already inherently non-linear, this task is further complicated
      by four factors: 1) the combination of legs in stance varies continuously. 2)
      during curve walking, legs must move at different speeds, 3) on compliant
      substrates, the speed of the individual legs may vary unpredictably, and 4) the
      geometry of the system may vary through growth and injury or due to non-rigid
      suspension of the joints. This task appears to require some kind of "motor
      intelligence". We show that an extremely decentralized, simple controller, based
      on a combination of negative and positive feedback at the joint level, copes with
      all these problems by exploiting the physical properties of the system.

PMID- 9755519
TI  - Non-linear mechanisms in the brain.
AB  - Non-linear dynamical models of brain activity can describe the spontaneous
      emergence of large-scale coherent structures both in a temporal and spatial
      domain. We discuss a number of discrete time dynamical neuron models that
      illustrate some of the mechanisms involved. Of special interest is the phenomenon
      of spatio-temporal stochastic resonance in which coherent structures emerge as a
      result of the interaction of the neuronal system with external noise at a given
      level punitive data. We then discuss the general role of stochastic noise in
      brain dynamics and how similar concepts can be studied in the context of networks
      of connected brains on the Internet.

PMID- 9755520
TI  - Accurate spike synchronization in cortex.
AB  - In view of the enormous capacity and complexity of mammalian brains it is evident
      that a detailed account of their anatomy and physiology alone cannot lead to a
      complete understanding of their function. Computer simulation and mathematical
      analysis of abstract, yet biologically realistic models for neurons and networks
      yield additional and useful information about the interplay of the underlying
      anatomical structures, the physiological processes operating on the neuronal
      substrate, and the resulting brain functions during the performance of behavioral
      tasks. We discuss some contributions of such experiment-guided theory to the
      issue of accurate spike synchronization.

PMID- 9755521
TI  - Solutions for the binding problem.
AB  - Visual cortical neurons are broadly tuned to one or a few feature dimensions,
      like color and motion. This is advantageous because broadly tuned neurons can
      contribute to the representation of many visual scenes. However, if there are
      multiple objects in a visual scene, the cortex is at risk to combine features of
      different objects as if they belong to a single object. The term "binding
      problem" was introduced to refer to the difficulties that may occur in sorting
      out those responses that are evoked by a single perceptual object. The present
      article reviews proposals suggesting that the binding problem is solved by
      labelling an assembly of neurons that is responsive to a single perceptual
      object. Evidence is reviewed in favor of two possible assembly-labels: rate
      enhancement due to visual attention and neuronal synchrony. Assembly-labels
      should be spread through the cortical network to all neurons that have to
      participate in an assembly. The present article tries to shed light on the
      mechanisms that subserve such a selective spread of assembly labels. Moreover, it
      is suggested that assembly labels may fulfill an equivalent role in the motor
      system, since binding problems can also occur during the generation of useful
      patterns of motor activity.

PMID- 9755522
TI  - Networks of gene regulation, neural development and the evolution of general
      capabilities, such as human empathy.
AB  - A network of gene regulation organized in a hierarchical and combinatorial manner
      is crucially involved in the development of the neural network, and has to be
      considered one of the main substrates of genetic change in its evolution. Though
      qualitative features may emerge by way of the accumulation of rather unspecific
      quantitative changes, it is reasonable to assume that at least in some cases
      specific combinations of regulatory parts of the genome initiated new directions
      of evolution, leading to novel capabilities of the brain. These notions are
      applied, in this paper, to the evolution of the capability of cognition-based
      human empathy. It is suggested that it has evolved as a secondary effect of the
      evolution of strategic thought. Development of strategies depends on abstract
      representations of one's own possible future states in one's own brain to allow
      assessment of their emotional desirability, but also on the representation and
      emotional evaluation of possible states of others, allowing anticipation of their
      behaviour. This is best achieved if representations of others are connected to
      one's own emotional centres in a manner similar to self-representations. For this
      reason, the evolution of the human brain is assumed to have established
      representations with such linkages. No group selection is involved, because the
      quality of strategic thought affects the fitness of the individual. A secondary
      effect of this linkage is that both the actual states and the future perspectives
      of others elicit vicarious emotions, which may contribute to the motivations of
      altruistic behaviour.

PMID- 9755523
TI  - Emergence and the cognitive neuroscience approach to psychiatry.
AB  - In this paper, I introduce the philosophical notion of strong emergence and argue
      that it is almost exclusively applied to properties related to (conscious)
      subjective experience. Contrary to the still common attitude of refraining
      anxiously from these topics, I argue that we have a promising scientific approach
      to them: the cognitive neurosciences. I list a spectrum of interesting,
      potentially strongly emergent properties already investigated, and discuss the
      example of volition in more detail. Psychiatric disorders, like antisocial
      personality disorder, schizophrenia, and obsessive compulsive disorder, open new
      ways for understanding aspects of volition such as willed action, decision
      making, and agency. I conclude that the notion of strong emergence is only a
      preliminary label which, however, might be understood as a challenge for
      empirical scientists to explain and understand phenomena related to subjectivity
      and consciousness.

PMID- 9755524
TI  - Group report: influence of brain and computer design on the performance of
      natural and artificial organisms.

PMID- 9755526
TI  - [Current view of the indications for surgical treatment of congenital heart
      diseases].

PMID- 9755525
TI  - Group report: emergent properties of natural and artificial systems.

PMID- 9755527
TI  - [Evidence based cardiology in focus. Solid and robust cardiology practice].

PMID- 9755528
TI  - [Evidence based cardiology. I. Principles, rationale and applications of a new
      cardiology practice and critical analysis of the literature].

PMID- 9755530
TI  - [Cardiovascular diseases observed during follow-up of a group of patients with
      undetermined form of Chagas' disease].
AB  - PURPOSE: The aim of this study was to evaluate the cardiovascular outcome in
      patients with the undetermined form of Chagas' disease and whether or not it is
      related to the infectious disease in the long-term. METHODS: One hundred and
      sixty patients were prospectively followed-up at three month intervals for up to
      177 months. RESULTS: Twenty and three (14.4%) patients developed hypertension
      complicated by ischemic stroke in two (1.2%) and symptomatic heart failure in one
      (0.6%). Cardiac arrhythmias occurred in four (2.4%) patients corresponding to
      isolated ventricular ectopic beats in two (1.2%), isolated supraventricular
      ectopic beats in one (0.6%) and an isolated episode of acute atrial fibrillation
      in another (0.6%). Two (1.2%) patients developed symptoms of coronary artery
      disease, one of them had one episode of acute chest pain diagnosed as myocardial
      infarction and the other had chronic chest pain diagnosed as angina. CONCLUSION:
      Hypertension is the most common cardiovascular disease occurring in the long-term
      follow-up of patients with the undetermined form of Chagas' disease. Cardiac
      rhythm disturbances and coronary artery disease were not more frequent than those
      generally found in a healthy population. These data confirm a favorable long-term
      prognosis in patients with the undetermined form of Chagas' disease.

PMID- 9755529
TI  - [Heart failure at a large tertiary hospital of Sao Paulo].
AB  - PURPOSE: To study the incidence, main causes, aggravating factors and secondary
      diagnoses of heart failure (HF) during 1995 at the Instituto do Coracao of Sao
      Paulo. METHODS: Data from hospitalized patients according to the PRODESP data
      base were analyzed. The following data were studied; age, sex, principal and
      secondary diagnoses, surgical procedures and mortality. To analyze the data,
      tables according to sex, age and main cause were built. Analysis of variance and
      t test were employed to verify differences between groups. RESULTS: In 1995, 903
      out of 9620 patients were hospitalized due to HF. The majority were male (60.4%)
      and the patients' age was between two days and 98 years old (mean 52.6). Ischemic
      (32.6), dilated (25.8%) and valvar heart disease (22%) were the main causes of
      HF. 32.1% were submitted to correction of the HF main cause, specially those with
      valvar heart disease (62.3%). There was greater incidence of multiple diagnoses
      in aged patients. The mortality was greater in patients younger than 20 and in
      those older than 80 years old. CONCLUSION: The incidence of HF at INCOR during
      1995 was 9.38%. Ischemic myocardiopathy was the most frequent HF cause. The
      mortality was greater among children, probably because of heart disease
      complexity and, in the above-80 group due to the greater comorbidity.

PMID- 9755531
TI  - [Comparison of coronary arteriosclerosis in patients with myocardial infarction
      and angina pectoris].
AB  - PURPOSE: To compare the severity of the coronary heart disease and the presence
      of coronary risk factors between angina and myocardial infarction (MI) patients.
      METHODS: We studied 62 patients with MI and 129 with angina through coronary
      angiography to evaluate occlusion (lesion of 99% or 100%), extent (with a score
      of 0-5 derived by the number of vessels affected) and severity (3 groups of
      different stenosis degrees). Two experiment observers blindly interpreted the
      angiograms. RESULTS: Patients with MI had more occlusions (50% vs 13.2% [p <
      0.01]), more severity (79% vs 54.3% with > 90% stenosis [p < 0.02]) and more
      extent (2.0 vs 0.87; [p < 0.001]), even when controlled for current coronary risk
      factors and disease duration. Smoking was the only independent risk factor
      related to MI (p < 0.001). CONCLUSION: Among the studied patients, coronary heart
      disease extent and severity was greater in the MI group, as well as the
      prevalence smoking.

PMID- 9755532
TI  - [Electro-cardiographic correlation in the diagnosis of left ventricular
      hypertrophy].
AB  - PURPOSE: To compare the efficacy of four electrocardiographic criteria: Sokolov,
      Gubner, Cornell and Romhilt indexes, in the diagnosis of left ventricular
      hypertrophy (LVH) in hypertensive patients. METHODS: LVH was analyzed in the
      electrocardiogram of 30 ambulatory patients presenting with systemic arterial
      hypertension, classified as mild, moderate and severe, according to the following
      indexes: Sokolov > or = 35 mm, Gubner > or = 22 mm, Romhilt > or = 5 points and
      Cornell > or = 20 mm for women and 28 mm for men. Sensitivity, specificity,
      diagnostic accuracy and other diagnostic variables were determined Mass index of
      the left ventricle, > or = 98 g/m2 for women and > or = 120 g/m2 for men,
      obtained by echocardiography, was considered the gold standard for the diagnosis
      of LVH. RESULTS: When electrocardiographic criteria were considered separately,
      the Sokolov index showed the highest accuracy, with a sensitivity of 40%,
      diagnostic accuracy of 50% and specificity of 100%; the second most accurate
      index was Gubner, and Romhilt and Cornell indexes followed. When at least one of
      the indexes was positive, the sensitivity was 52% and diagnostic accuracy was
      57%. CONCLUSION: The four electrocardiographic indexes were not diagnostic of
      LVH, when analyzed either separately or together. Considering the high prevalence
      of this pathological condition, we conclude that a more accurate diagnostic
      method should be used in this diagnosis.

PMID- 9755533
TI  - [Catheter ablation of atrial flutter. Electrophysiological characterization of
      posterior and septal isthmus block].
AB  - PURPOSE: Evaluate the different types of conduction blocks obtained between
      inferior vena cava-tricuspid annulus (posterior isthmus) and between tricuspid
      annulus-coronary sinus ostium (septal isthmus) after radiofrequency (RF) catheter
      ablation of atrial flutter (AFL). METHODS: In 16 procedures, 14 patients (pts), 9
      male, with type I AFL underwent RF ablation. Atrial activation around tricuspid
      annulus was performed with a 10-bipole "Halo" catheter (H1-2; H19-20). In sinus
      rhythm, isthmus conduction was evaluated during proximal coronary sinus (PCS) and
      low lateral right atrium (H1-2) pacing, before and after linear ablation.
      According to the wave front of impulse propagation we assessed absence of block
      (bidirectional conduction); incomplete block (bidirectional conduction with delay
      in one front of impulse propagation) and complete block (absence of conduction).
      The PCS/H1-2 interval was measured before and after ablation. RESULTS: Complete
      isthmus block was achieved in 7 (44%) and incomplete block in 4 (25%) procedures.
      Conduction block was not achieved in 5 procedures. At a mean follow-up of 12
      months, there were no recurrences in the pts with complete block, whereas AFL
      recurred in the 6 pts with incomplete or no conduction block (p < 0.001). Pts
      with complete block had delta PCS/H1-2 interval (74.0 +/- 26.0 ms) greater than
      incomplete (30.5 +/- 7.5 ms) or absent block (p < 0.05). CONCLUSION: The
      verification of complete isthmus conduction block with atrial multipolar mapping
      is an effective strategy to assess electrophysiological success and absence of
      late recurrence in common atrial flutter ablation.

PMID- 9755534
TI  - [Contribution of dynamic electrocardiography by Holter monitoring in the
      evaluation of congenital long QT syndrome patients].
AB  - PURPOSE: The purpose of this study was to evaluate the value of ambulatory
      electrocardiogram as a clinical tool to assess ventricular repolarization in
      patients with the congenital long QT syndrome. METHODS: The study population
      comprised six patients and their data were compared to a control group of six
      patients matched in age and gender. The QT interval (ms), corrected by the heart
      rate, was measured in the first minute of each hour using two monitoring leads,
      with the mean of six consecutive complexes. The data obtained include the
      morphologic pattern of T wave, the mean 24-h QTc interval, relation between QT
      and cardiac cycle, QTc variability (assessed calculating hourly standard
      deviation of the interval and then obtaining the global 24-h mean), QTc
      dispersion (difference between the longest and shortest QTc interval). RESULTS:
      In all patients abnormal patterns of T waves were detected with frequent episodes
      of T wave alternans. Mean 24-h QTc--patients: 598.2 +/- 73.8 ms; controls: 436.1
      +/- 8.9 ms (p = 0.000). Linear correlation and regression between QT and heart
      rate-patients: r = 0.812; controls: r = 0.967 (p = 0.000). QTc variability
      patients: 36.9 +/- 17.2 ms; controls: 14.7 +/- 2.1 ms (p = 0.01). QTc dispersion
      patients: 168.3 +/- 70.2 ms; controls: 53.3 +/- 8.1 ms (p = 0.000). CONCLUSION:
      The data showed increased hourly QTc variability. QTc dispersion and worse
      correlation between QT and heart rate. This data may reflect an abnormally
      augmented ventricular vulnerability.

PMID- 9755535
TI  - [Antihypertensive treatment. Prescription and cost of drugs. Survey in a tertiary
      care hospital].
AB  - PURPOSE: To study the most prescribed anti-hypertensive drugs, evaluating their
      agreement with established guidelines and drug cost. METHODS: One hundred and
      forty one (101 women, mean age = 53.3 years) hypertensive patients who searched
      spontaneous attention were interviewed in a tertiary-care hospital. The inclusion
      criteria were previous diagnosis of hypertension and non cardiovascular
      complaints. RESULTS: The majority of the 107 (75.9%) patients were on medical
      treatment. In those receiving monotherapy, thiazides were the most utilized
      drugs, followed by methyldopa, ACE inhibitors, calcium channel-blockers, and beta
      blockers. The association with thiazides (26.3%) followed the same preference.
      The second most prescribed drug, methyldopa, was the more expensive. Fifty
      percent of the patients purchased the drugs at their own expense. CONCLUSION: A
      preference for prescription of expensive drugs for hypertension was detected in
      this sample in Brazil. This does not agree with major guidelines, mainly the V
      JNC, which suggest thiazides and betablockers as first choice drugs for
      hypertensives with no complications or associated comorbidity.

PMID- 9755537
TI  - [Aneurysm of arterial duct associated to aortic arch interruption].
AB  - Aneurysm of the arterial duct is an infrequent finding, which is very rarely
      detected prenatally. A case of antenatal diagnosis in a pregnant patient (33
      weeks) is reported. The fetus presented an aneurysmatic dilation of the arterial
      duct with uniformly enlarged diameter, inserting into the descending aorta, which
      was interrupted. The neonate was born by cesarean section and was kept on
      postaglandins till the 9th day of life, when he was sent to surgery. During the
      surgical procedure, the baby died as a result of biventricular failure. This is
      the first report of prenatal association of aneurysm of the ducts anteriosus with
      other cardiovascular malformations and emphasizes that this finding does not
      always have a benign course.

PMID- 9755536
TI  - [Single balloon versus Inoue balloon in percutaneous mitral balloon
      valvuloplasty. Short-term results and complications].
AB  - PURPOSE: To assess short-term results and complications of percutaneous mitral
      balloon valvuloplasty (PMBV) performed with Inoue balloon (IB) and single low
      profile balloon (SB). METHODS: We performed 390 PMBV procedures, 29 with IB and
      337 with SB. There were no differences in age, sex, echocardiographic score
      distribution and echocardiographic mitral valve area (MVA). RESULTS: We performed
      29 complete procedures with IB and 330 of 337 in SB group. Comparing IB and pre
      and pos-PMBV data we obtained: mean pulmonary artery pressure (MPAP) 36 +/- 15
      and 39 +/- 14 mmHg, p = 0.2033, mean mitral gradient 17 +/- 6 and 20 +/- 77 mmHg,
      p = 0.0396 and MVA 0.9 +/- 0.2 and 0.9 +/- 0.2 cm2, p = 0.8043 and pos-PMBV:MPAP
      25 +/- 8 and 28 +/- 10 mmHg, p = 0.2881, gradient 5 +/- 3 and 5 +/- 4 mmHg, p =
      0.2778 and MVA 2.2 +/- 0.2 and 2.0 +/- 0.4 cm2, p = 0.0362. Mitral valve (MV) was
      competent in 26 patients in IB and in 280 in SB group and we had +/4 mitral
      regurgitation in 3 patients in IB and in 57 in SB group (p = 0.3591) pre-PMBV
      respectively and pos-PMBV there was also no difference in MV competence (p =
      0.7439). CONCLUSION: Both techniques were effective. Hemodynamic data were also
      similar although MVA was greater in IB group after PMBV.

PMID- 9755538
TI  - [Hyperhomocysteinemia and vaso-occlusive diseases].

PMID- 9755540
TI  - [Effect of eggplant on plasma lipid levels, lipidic peroxidation and the
      reversion of endothelial dysfunction in experimental hypercholesterolemia].

PMID- 9755539
TI  - [Stents. Review of the literature].

PMID- 9755541
TI  - [Effect of eggplant on plasma lipid levels, lipidic peroxidation and the
      reversion of endothelial dysfunction in experimental hypercholesterolemia].

PMID- 9755542
TI  - [Teaching at the bedside--a solid truth].

PMID- 9755543
TI  - [Efficacy of and tolerance to salmeterol compared to salbutamol in patients with
      bronchial asthma].
AB  - Beta 2-agonists are considered one of the cornerstones of the asthma therapy, but
      their short action requires frequent administration and an association with other
      broncodilators. The development of long-acting beta 2-agonists may represent an
      important improvement in asthma treatment. PURPOSE: The present study was
      designed to assess the efficacy and safety of inhaled salmeterol compared to
      salbutamol in patients with mild-to-moderate asthma. METHODS: After the two run
      in weeks, the patients received either salmeterol 50 mg twice a day or salbutamol
      200 mg four times a day, over a four week period, following a double blind,
      parallel group study. Sixty patients had the following inclusion criteria: FEV1 >
      50% or PEFR over the past seven days > 50% of predicted normal; reversibility of
      FEV1 > 15%; symptoms scores > 2 (score 0 and 5) in 4 of the last seven days or
      PEFR variation > 15%. RESULTS: Seven patients discontinued the protocol (see
      methods). Of the 53 analyzable patients, 25 were of the salmeterol group and 28
      of the salbutamol group. Our results showed that in the run-in period there were
      not differences among the groups comparing the values of FEV1 in % predicted,
      morning PEFR and asthma symptoms scores. The improvement rate of morning FEV1 and
      PEFR in patients who received salmeterol was significantly higher (p < 0.05)
      compared to the patients who received salbutamol, for two and four weeks of
      treatment. Also, the salmeterol group have shown reduction of the symptoms in the
      nocturnal period(significantly in the first fortnight of treatment) demonstrated
      by the significative increase in the symptoms improvement rate when compared
      salmeterol and to salbutamol groups. The number of rescue medication inhaled,
      side effects, heart rate, blood pressure, serum potassium dosage and
      electrocardiograms, did no show significative differences between the groups.
      CONCLUSION: This study showed that in mild to moderate asthmatic patients,
      salmeterol in the dosage of 100 mg/day raised the FEV1 and the morning PEF and
      led to pronounced decrease in the nocturnal symptoms as compared to salbutamol.
      The side effects were similar.

PMID- 9755544
TI  - [Measuring cyclosporine levels in whole blood in kidney transplantation].
AB  - BACKGROUND: Cyclosporin A is a potent immunosuppressive drug effective in
      combatting rejection following organ transplantation. In na effort to replace a
      radioimmunoassay (RIA) for whole blood determination of cyclosporine (Cya) we
      compared RIA with fluorescence polarization immunoassay (FPIAm). METHOD: 65 blood
      samples were analysed from kidney transplanted patients. The samples were
      collected into tubes containing EDTA as anticoagulant and analysed by RIA and
      FPIAm. RESULTS: The statistical analysis revealed a difference between both
      methods (p < 0.05). The linear-regression comparison of Cya concentration
      measured by RIA and FPIAm showed the following relationship: Cya(FPIAm) = 1.06 x
      Cya(RIA) + 5.8 (r = 0.9817). CONCLUSION: We conclude that FPIAm provides na
      alternative method for measuring cyclosporine in whole blood with the added
      advantages of being reasonably rapid, precise and easy to perform.

PMID- 9755545
TI  - [Technical aspects of esophagocardiomyotomy with divulsion for the surgical
      treatment of non advanced chagasic megaesophagus].
AB  - BACKGROUND: The authors describe a Heller's technique alteration used for
      treatment of early Chagasic megaesphagus (ECM): esophagocardiomyotomy with
      divulsion plus esophagocardiopexy. PATIENTS AND METHODS: Between June 1988 and
      March 1996, fifty patients were operated on at Surgery Department of FAMEMA. All
      had chagasic megaesophagus degrees I, II and III. RESULTS: The results were
      excellent in 86% (43/50) and good in 14% (7/50), for 6 months to 7.6 years of
      follow up. The radiological and endoscopic studies showed neither esophagic
      stasis nor food residues and esophagitis. CONCLUSION: The authors concluded that
      esophagocardiomyotomy with divulsion plus esophagocardiogastropexy is efficient
      in ECM degrees I, II e III and emphasize both technical facility and security.

PMID- 9755546
TI  - [Immunological indicators (IgM and C-reactive protein) in neonatal infections].
AB  - Sepsis in the neonatal age is associated with risk factors for infections and
      with the immunological state of the newborn infant. BACKGROUND: Verify if IgM and
      C-reactive protein were indicators of infection in newborn infants with risk
      factors. MATERIAL AND METHODS: We studied 57 newborn infants that had: premature
      rupture of amniotic membranes associated ou no with clinical amniotics or with
      urinary tract infection. They were classified in three gestational age groups (<
      34 weeks, between 34-36 6/7 and (37 weeks) Sepsis diagnosis was made through
      clinical and laboratorial criterious and we also included: IgM and C-reactive
      protein obtained of the newborn at birth and at fifth day of life. RESULTS:
      Sepsis diagnosis was made in 18 (31.5%) of 57 newborn infants, 13 (22.8%) with
      early sepsis and 5 (8.7%) with late sepsis. The infection had statistical
      association with gestational age and with weight at birth. The gestational group
      < 34 weeks was more infected and in this group the number of newborn that died
      had association with infection. We did not observed association in the three
      groups studied between infection and sex. There were significant differences of
      levels of IgM between infected and not infected newborn infants in the same group
      of gestational age, this difference was more evident in the fifth day. There were
      association between levels of C-reactive protein > 10 mg/L and infection in the
      three groups studied. CONCLUSION: C-reactive protein was the better indicator of
      infection at birth and in the fifth day of life and this was very important for
      the clinical evolution of the infection and in the late sepsis was the first
      prove that was altered.

PMID- 9755547
TI  - [Increase in the frequency of norfloxacin and ciprofloxacin resistance of
      bacteria isolated from urine culture].
AB  - OBJECTIVE: To assess time trends in the frequency of norfloxacin and
      ciprofloxacin resistance of bacteria isolated from urine culture. METHODS:
      Results of all urine cultures with a bacterial growth of at least 10(5) colony
      forming units per milliliter, performed at the Renal Service of the Federal
      University of Bahia, Brazil, from 1983 to 1994 were analyzed. The bacteria
      considered for this analysis were those most often isolated: Escherichia coli (n
      = 668), Klebsiella spp. (n = 286), Staphylococcus spp. (n = 186), Proteus spp. (n
      = 135) and Enterobacter spp. (n = 129). RESULTS: The frequencies of norfloxacin
      resistance for the periods 1983-1986, 1987-1990 and 1991-1994 were 3.2%, 5.9% and
      9.1%, respectively (p-value < 0.05). The most pronounced increases in the
      frequencies of norfloxacin-resistance were observed for Klebsiella spp. and
      Enterobacter spp. The frequency of ciprofloxacin resistance was 7.4% in the
      period 1985-1989 and 16.5% in the period 1990-1994 (p-value < 0.05). This time
      trend in ciprofloxacin resistance was more striking for Enterobacter spp. and
      Staphylococcus spp. CONCLUSION: The results show a gradual increase in the
      frequency of norfloxacin and ciprofloxacin resistance of the bacteria most
      commonly isolated from urine cultures. The influence of previous treatment with
      quinolones and characteristics of the infecting bacteria on these findings are
      important questions to to be addressed in future investigations.

PMID- 9755548
TI  - [Blood component transfusion in full-term and premature new born infants].
AB  - BACKGROUND: Blood transfusion requirements for preterm infants are greater than
      for newborn ones. We compare blood transfusion requirements for newborn and
      premature infants and their pathology: clinical or surgical; hemorrhagic
      accidents and survival. METHODS: 48 newborns classified in 2 groups: 26 newborn
      and 22 preterm infants received 251 units of blood components: 177 units of red
      cell concentrates, 36 of platelet concentrates, 30 of fresh frozen plasma and 8
      of total blood in a 186 days period. We analyzed total requirements of components
      in each group and daily, under a live-infant/day rate until 120 days. RESULTS:
      The all-components median requirements were 7.31 units for premature and 3.46 for
      newborn infants. Daily requirements analyzes reveal that requirements were
      greater before 60th day of life (d.l.) on clinical patients and after 86th d.l.
      may be caused by surgical acts. Hemorrhagic accidents happen on premature with
      less than 60,000 platelets/mm3. The survival wave by number of transfusions,
      until 186 d.l., show an inversely proportional trend between the number of
      transfusions done and the hope of life. CONCLUSIONS: Blood requirements for
      preterm infants are greater than for term ones. Those requirements are related to
      their pathology. Prophylatic platelet transfusions may reduce hemorrhagic
      accidents then red blood cell transfusions in preterm infants group. The number
      of transfusions over 10 is a surrogate marker of bad prognosis for both groups up
      to 120 d.l.

PMID- 9755549
TI  - [Frequency of stenosis of renal the artery in 676 renal transplantations].
AB  - Kidney transplantation is the permanent and safe treatment for patients with
      chronic renal failure, although surgical treatment is susceptible both to
      urological and many vascular complications, and post-transplantation, renal
      artery stenosis being the most important. OBJECTIVE: To verify the incidence of
      renal artery stenosis of 676 patients submitted to renal transplants, from living
      and cadaver donors, in the period of February of 1985 to December of 1994, when
      compared the end-to-end and end-to-side anastomosis with the external iliac
      artery of the recipient. METHODS: The data shown were obtained from charts of 676
      patients submitted to renal transplants performed by the same surgery staff at
      the Hospital Sao Paulo--Universidade Federal de Sao Paulo--Escola Paulista de
      Medicina, between 1985 and 1994. RESULTS: Eleven cases (1.63%) of post
      transplantation renal artery stenosis were found. CONCLUSION: 1) Frequency of
      post-transplantation renal artery stenosis was low and observed only in
      recipients of cadavers donors. 2) Frequency of post-transplantation renal artery
      stenosis with end-to-end artery anastomosis did not significantly differ from end
      to-side anastomosis. 3) Age, sex and ethnic groups of patients did not interfere
      in the frequency of renal artery stenosis.

PMID- 9755550
TI  - [Development of puberty in girls treated for acute lymphocytic leukemia].
AB  - BACKGROUND: In order to evaluate the puberal development of girls treated by
      Acute Lymphocytic Leukaemia (ALL) a retrospective study was done at Campinas-SP,
      Brazil. MATERIAL AND METHODS: Forty two girls were treated by ALL with either 18
      or 24 Grays of cranial irradiation. All patients were treated with chemotherapy
      including intrathecal methotrexate in similar dose regimens in either groups.
      RESULTS: The results showed lower mean ages at telarche, pubarche and menarche in
      the treated group, mainly in the group treated before five years old. No
      differences were observed in the 18 Grays or 24 Grays group. CONCLUSIONS: Our
      data suggest that girls treated by ALL have a precocious puberal development.

PMID- 9755551
TI  - [Surgical removal of pulmonary metastasis: prospective study in 182 patients].
AB  - PURPOSE: The present study evaluates the results of surgical treatment of lung
      metastases, as well as attempts to identify subgroups of patients who would
      benefit the most from the operation. CASE AND METHODS: This is a prospective
      analysis of patients with history of neoplasia, submitted to resection of
      pulmonary nodules, with the diagnosis or suspicion of metastases. The 182
      patients were operated upon through a lateral thoracotomy. RESULTS: The patients
      submitted to pulmonary resection for suspected metastases showed no malignant
      tissue in 34 patients (18.6%), and in six patients (3.2%) were diagnosed a second
      lung primary tumor. Overall survival of the patients was 28% at 56 months, and
      disease-free survival was 9%. Multivariate analysis showed that disease free
      interval (p = 0.002), complete resection (p = 0.039), and number of malignant
      nodules resected (p = 0.016) significantly affected overall survival. Disease
      free survival was affected only by complete resection (p = 0.0001) and number of
      malignant nodules resected (p = 0.004). CONCLUSION: Resection of pulmonary
      metastasis improve survival in a selected group of patients. More studies are
      necessary to define the value of other therapies in the results of survival in
      resected pulmonary metastasis.

PMID- 9755552
TI  - [Cholangiopancreatography with magnetic resonance: a new approach for assessing
      the bile and pancreatic ducts].

PMID- 9755553
TI  - [Chest pain in patients with normal coronary angiography (syndrome X): new
      concepts].

PMID- 9755554
TI  - [Work shifts, sleep and biological rhythms].

PMID- 9755555
TI  - [Lung volume reduction--surgical alternative to the treatment of severe diffuse
      pulmonary emphysema?].

PMID- 9755556
TI  - [Ph1-positive acute myeloid leukemia de novo or blast crisis of chronic myeloid
      leukemia? Molecular analysis and clinical course of a case].
AB  - A case of AML presented with basophilia in peripheral blood and Ph1 chromosome in
      karyotype analysis is reported. After one year of treatment with intensive
      chemotherapy and clinical and hematological remission, molecular analysis (RT
      PCR) detected minimal residual disease (b2-a2 rearrangement). Thus, the patient
      relapsed as AML and, after second remission, he developed a hematological picture
      of chronic CML. Ten months later, he relapsed again as AML. The difficulties of
      diagnosis between AML Ph1-positive de novo and myeloid blast crisis of CML, as
      the first manifestation of disease, based on clinical and molecular aspects are
      discussed.

PMID- 9755557
TI  - [Reconstructive surgery of the lower lip with esthetic-functional recovery:
      report of 2 cases].
AB  - Two cases of patients with large squamous cell carcinoma in the lower lip, that
      were submitted to the reconstructive surgery, using technique of lateral progress
      with reconstruction of the red lip, always tends the concern of the recovery not
      only functional as well as aesthetic of these patients ones, are reported. A
      classification is given suggesting the main locations of the squamous cell
      carcinoma of the lip, allowing better definition with relationship to the
      surgical technique to be used in each case, depending on the location and
      involvement or not of the lip comissure.

PMID- 9755558
TI  - Meningococcal disease caused by Neisseria meningitidis serogroup B serotype 4 in
      Sao Paulo, Brazil, 1990 to 1996.
AB  - A large epidemic of serogroup B meningococcal disease (MD), has been occurring in
      greater Sao Paulo, Brazil, since 1988. A Cuban-produced vaccine, based on outer
      membrane-protein (OMP) from serogroup B: serotype 4: serosubtype P1.15
      (B:4:P1.15) Neisseria meningitidis, was given to about 2.4 million children aged
      from 3 months to 6 years during 1989 and 1990. The administration of vaccine had
      little or no measurable effects on this outbreak. In order to detect clonal
      changes that could explain the continued increase in the incidence of disease
      after the vaccination, we serotyped isolates recovered between 1990 and 1996 from
      834 patients with systemic disease. Strains B:4:P1.15, which was detected in the
      area as early as 1977, has been the most prevalent phenotype since 1988. These
      strains are still prevalent in the area and were responsible for about 68% of 834
      serogroup B cases in the last 7 years. We analyzed 438 (52%) of these strains by
      restriction fragment length polymorphism (RFLPs) of rRNA genes (ribotyping). The
      most frequent pattern obtained was referred to as Rb1 (68%). We concluded that
      the same clone of B:4:P1.15-Rb1 strains was the most prevalent strain and
      responsible for the continued increase of incidence of serogroup B MD cases in
      greater Sao Paulo during the last 7 years in spite of the vaccination trial.

PMID- 9755559
TI  - Frequency of dermatophytes in the metropolitan area of Porto Alegre, RS, Brazil.
AB  - In order to evaluate the distribution of dermatophytes in Porto Alegre, the
      capital of the state of Rio Grande do Sul, Brazil, they were isolated from the
      skin, hairs and nails samples and retrospectively analyzed from June 1981 to June
      1995, in two different institutions in the city of Porto Alegre: (i) the Servico
      de Micologia do Instituto de Pesquisas Biologicas Jandyr Maya Faillace, da
      Secretaria de Saude e Meio Ambiente do Rio Grande do Sul which attends the low
      income population (low and middle classes) and, (ii) Laboratorio Weinmann, a
      clinical pathology laboratory which attends predominantly the higher income
      population (middle and upper classes), both which attend in the metropolitan area
      of Porto Alegre. The dermatophyte predominance of Trichophyton rubrum was
      confirmed (55.33%) followed by T. mentagrophytes (21.46%). The data obtained were
      compared with the existing prevalence data which were collected in the interior
      of the state over a period of 32 years (1960-1992). T. verrucosum, T. simii,
      Microsporum persicolor, T. schoenleinii, M. nanum and M. cookei were isolated in
      the interior and have not been found in the capital so far. On the other side, T.
      violaceum was, isolated in the capital and has not been found in the interior so
      far.

PMID- 9755560
TI  - Evolution of IgG antibody response against Toxoplasma gondii tissue cyst in acute
      and chronic human infections.
AB  - The recognition profile of the tissue cysts antigens by IgG antibodies was
      studied during acute and chronic human toxoplasmic infection. Thus the IgG
      response against Toxoplasma gondii was investigated by immunoblotting in two
      patients accidentally infected with the RH strain as well as in group of
      naturally infected patients at acute and chronic phase. There was an overall
      coincidence of molecular mass among antigens of tachyzoites and tissue cysts
      recognized by these sera, however, they appear not to be the same molecules. The
      response against tissue cysts starts early during acute infection, and the
      reactivity of antibodies is strong against a wide range of antigens. Six bands
      (between 82 and 151 kDa) were exclusively recognized by chronic phase sera but
      only the 132 kDa band was positive in more than 50% of the sera analysed. A
      mixture of these antigens could be used to discriminate between the two infection
      phases. The most important antigens recognized by the acute and the chronic phase
      sera were 4 clusters in the ranges 20-24 kDa, 34-39 kDa, 58-80 kDa and 105-130
      kDa as well as two additional antigens of 18 and 29 kDa. Both accidentally
      infected patients and some of the naturally infected patients showed a weak
      specific response against tissue cyst antigens.

PMID- 9755561
TI  - A comparative epidemiologic study of specific antibodies (IgM and IgA) and
      parasitological findings in an endemic area of low transmission of schistosoma
      mansoni.
AB  - The diagnostic potential of circulating IgM and IgA antibodies against
      Schistosoma mansoni gut-associated antigens detected by the immunofluorescence
      test (IFT) on adult worm paraffin sections was evaluated comparatively to the
      fecal parasitological method, for epidemiological purposes in low endemic areas
      for schistosomiasis. Blood samples were collected on filter paper from two groups
      of schoolchildren living in two different localities of the municipality of
      Itariri (Sao Paulo, Brazil) with different histories and prevalences of
      schistosomiasis. The parasitological and serological data were compared to those
      obtained for another group of schoolchildren from a non-endemic area for
      schistosomiasis. The results showed poor sensitivity of the parasitological
      method in detecting individuals with low worm burden and indicate the potential
      of the serological method as an important tool to be incorporated into
      schistosomiasis control and vigilance programs for determining the real situation
      of schistosomiasis in low endemic areas.

PMID- 9755562
TI  - Questionnaires in the screening for Schistosoma mansoni infection: a study of
      socio demographic and water contact variables in four communities in Brazil.
AB  - The use of questionnaires has been recommended for identifying, at a lower cost,
      individuals at risk for schistosomiasis. In this study, validity of information
      obtained by questionnaire in the screening for Schistosoma mansoni infection was
      assessed in four communities in the State of Minas Gerais, Brazil. Explanatory
      variables were water contact activities, sociodemographic characteristics and
      previous treatment for schistosomiasis. From 677, 1474, 766 and 3290 individuals
      eligible for stool examination in the communities, 89 to 97% participated in the
      study. The estimated probability of individuals to be infected, if they have all
      characteristics identified as independently associated with S.mansoni infection,
      varied from 15% in Canabrava, to 42% in Belo Horizonte, 48% in Comercinho and 80%
      in Sao Jose do Acacio. Our results do not support the hypothesis that a same
      questionnaire on risk factors could be used in screening for S.mansoni infection
      in different communities.

PMID- 9755563
TI  - Rubber contact dermatitis in patients attended at Walter Cantidio Hospital,
      Federal University of Ceara, Brasil.
AB  - Nowadays 70% of the world's rubber supply is synthesized artificially. The
      process involved in its manufacture is vulcanization which requires many chemical
      substances for speeding the process, as antioxidants to prevent deterioration of
      rubber, or others. These substances may constitute important sensitizers and thus
      be responsible for dermatological diseases like contact dermatitis. The objective
      of this study is to search for the main sensitizers among these rubber chemicals
      in a population mostly composed by women of a tropical country and compare the
      results with the ones obtained from previous studies which tested populations
      mainly composed by men and on different climates.

PMID- 9755564
TI  - Duality of patterns in hepatitis A epidemiology: a study involving two
      socioeconomically distinct populations in Campinas, Sao Paulo State, Brazil.
AB  - To evaluate the prevalence of antibodies against hepatitis A in two
      socioeconomically distinct populations, 101 and 82 serum samples from high and
      low socioeconomic groups, respectively, were analysed for the presence of IgG
      anti-HAV using a commercial ELISA. The prevalence in low socioeconomic level
      subjects was 95.0%, whereas in high socioeconomic subjects was only 19.6% (p <
      0.001). These data show a duality in Brazil: anti-HAV prevalence in low
      socioeconomic subjects is similar to that of developing countries, while in high
      socioeconomic subjects, a pattern typical of developed countries is found. The
      control of this infection in our country is primarily related to the improvement
      of sanitation, but especially for high socioeconomic level populations, the use
      of vaccination against hepatitis A is strongly advisable to avoid the occasional
      appearance of this disease in adults.

PMID- 9755565
TI  - The control of anopheline mosquitos by the spraying of Deltamethrin on raffia
      curtains used in miners' huts in areas endemic for malaria.
AB  - The residual potential of an aqueous solution of Deltamethrin (FW 25 mg i.a./m)
      was evaluated on raffia curtains. These are sheets of synthetic material used in
      the construction of huts to house miners. Experiments were conducted during 420
      days and the curtains were always rolled up in the daytime and unrolled in late
      afternoon. Data analyzed by logarithmic regression indicated that raffia treated
      with Deltamethrin had higher mortality indices than that covered with DDT. The
      residual capacity of Deltamethrin on raffia was high. The mortality percentage
      was above 85% after 360 days and dropped to about 50% at 420 days. The effect of
      DDT was reduced after 180 days and reached zero by the end of the experiment.
      Based or the results of these experiments, it is recommended that Deltamethrin be
      used to spray raffia curtains in mining regions and other areas that are endemic
      for malaria.

PMID- 9755566
TI  - The use of oligonucleotide probes for meningococcal serotype characterization.
AB  - In the present study we examine the potential use of oligonucleotide probes to
      characterize Neisseria meningitidis serotypes without the use of monoclonal
      antibodies (MAbs). Antigenic diversity on PorB protein forms the bases of
      serotyping method. However, the current panel of MAbs underestimated, by at least
      50% the PorB variability, presumably because reagents for several PorB variable
      regions (VRs) are lacking, or because a number of VR variants are not recognized
      by serotype-defining MAbs. We analyzed the use of oligonucleotide probes to
      characterize serotype 10 and serotype 19 of N. meningitidis. The porB gene
      sequence for the prototype strain of serotype 10 was determined, aligned with 7
      other porB sequences from different serotypes, and analysis of individual VRs
      were performed. The results of DNA probes 21U (VR1-A) and 615U (VR3-B) used
      against 72 N. meningitidis strains confirm that VR1 type A and VR3 type B encode
      epitopes for serotype-defined MAbs 19 and 10, respectively. The use of probes for
      characterizing serotypes possible can type 100% of the PorB VR diversity. It is a
      simple and rapid method specially useful for analysis of large number of samples.

PMID- 9755567
TI  - Hemorrhagic syndrome and acute renal failure in a pregnant woman after contact
      with Lonomia caterpillars: a case report.
AB  - A case of a 37-week pregnant woman who developed a hemorrhagic syndrome and acute
      renal failure after contact with Lonomia caterpillars is reported. The accident
      also initiated labour and the patient gave birth to an alive child. Some
      pathophysiological aspects of the genital bleeding and of the acute renal failure
      are discussed.

PMID- 9755568
TI  - An unusual ground larval habitat of Aedes albopictus.

PMID- 9755569
TI  - Immune response and severity of pulmonary tuberculosis in children.

PMID- 9755570
TI  - [The classical or laparoscopic operation in inguinal hernias].
AB  - AIM: Results evaluation in two trials of patients undergoing classical or
      laparoscopic surgery for inguinal hernia. MATERIAL AND METHOD: We compared 2
      homogeneous trials of 80 patients with inguinal hernias treated by classic
      procedures: Bassini, Shouldice, Lichtenstein (trial I) or by laparoscopic
      approach with Plastex, Mercilene or Prolene prosthesis (trial II) between 1995
      1997. RESULTS: Postoperative morbidity consisted in trial I in 5 seromas, 2
      hematomas, 4 cases with neuralgic pain, 1 with testicular hypotrophy and 4
      recurrences. In this trial the mean operative time was 22 min. and the mean
      hospitalization was 7 days. In trial II we registered a parietal bleeding at a
      lateral port imposing the conversion, 3 serohematomas, 2 recurrences by
      displacement of the prosthesis and 2 cases of neurologic pain. The mean operative
      time was 50 minutes and the mean hospitalization was 3 days. CONCLUSION: In spite
      of the longer operative time and the higher cost (the price of the prosthesis),
      in trial II the benefits of shorter hospitalization, lower morbidity and rapid
      socioprofessional reintegration are significant.

PMID- 9755571
TI  - [The laparoscopic approach to the retroperitoneal space].

PMID- 9755572
TI  - [The indications for and limits to the surgical treatment of congenital
      dilatations of the intra- and extrahepatic bile ducts].
AB  - Congenital cystic dilatations of the biliary ducts are defects in the genetic
      program which are transmitted in an autosomal recessive way. Todani classified
      cystic dilatations of extra and intrahepatic ducts in 5 types. In classified
      cystic dilatations of extra and intrahepatic ducts in 5 types. In "N. Gh. Lupu"
      Surgical Clinical were treated 9 cases of congenital dilatations of the biliary
      tree during the last 40 years (1958-1998); five of them were belonging to the
      type V Todani (Caroli's disease), three to the type I Todani and one case in the
      type IV a of Todoni's classification. The mean age of the patients was 42.4
      years, five of them being men and 4 women. Surgical treatment was particular to
      each case depending on age, associated diseases, the length of disease's
      evolution and the general state of the patient. The prognosis of this disease is
      a reserved one.

PMID- 9755574
TI  - [Occult breast cancer].
AB  - In 20 years we registered seven observations of breast cancer presenting as an
      axillary mass (BCAM), meaning 0.9% out of the global breast cancer series (767
      cases). All the cases were females. The main clinical sign was only the presence
      of axillary lymph nodes. Diagnosis was precised by the pathological examination
      of the excised nodes (six observations) or needle aspiration of the axillary
      lymph nodes. Mammography showed tumors less than one centimeter in three out of
      the seven cases. As for the stadialisation, we had two cases in the II-nd stage,
      four patients in the III-rd stage and one in IV-th. All the patients were
      operated on. There were four simple mastectomies anti three Patey radical
      modified mastectomies. Postoperative chemotherapy and radiotherapy were performed
      to all the patients. Only two of the seven patients survived five years after
      surgery.

PMID- 9755573
TI  - [A plea for the conservative treatment of breast cancer].
AB  - This article is a plea for the implementation of early-stage breast cancer
      conservative therapy into as many surgical clinics as possible. The
      aforementioned statement relies mainly on published papers and data (the protocol
      included) provided to us by Instituti Clinici di Perfezionamento di Milano
      experts in breast cancer conservative therapy and to a lesser extent on our not
      too numerous results (30 cases) obtained over the past 2 years since we applied
      the Milano protocol on a regular basis. Thus we support the view that the breast
      conserving treatment is suitable for clinical stage I or II carcinoma whose
      tumors are 3 cm or less in greatest diameter, provided axillary lymphadenectomy
      is associated for prognostic and future management guidance reasons, but not for
      cure. Breast-limited postoperative radiation treatment is foremost aimed at local
      recurrences rate reduction without significantly influencing survival rate.
      Postoperative chemotherapy, indicated for node-positive patients and/or primary
      tumors over 1 cm in greatest, diameter, has been proved to contribute to long
      term survival rate. However, both the small sample size and the short period of
      observation of our study prevented us from drawing firm conclusions directly.

PMID- 9755575
TI  - [The duodenal compression syndrome (DCS) due to an aorto-mesenteric shunt
      associated with primary intestinal malrotation].
AB  - It is presented the cases of a patient suffering from a rare surgical condition,
      Wilkie's syndrome, duodenal compression syndrome through aorto-mesenteric clamp,
      also known as the superior mesenteric artery syndrome (SMAS). The authors wish to
      underline the diagnosis difficulties which concurred to a delay of surgical cure,
      also presenting the surgical technique methods used for solving this case. Among
      the large number of operations till now proposed for the management of this
      syndrome, the chosen solution-resection of the first jejunal loop together with
      the duodenojejunal junction followed by prevascular lateroterminal duodenojejunal
      anastomosis--was imposed by the coexistence of an intestinal malrotation, forming
      the so called "common mesentery".

PMID- 9755576
TI  - [Rectal hemangioma--a pseudoneoplastic form. A case report and review of the
      literature].
AB  - A patient, 23 years old, is presented. He was admitted on in our clinic for a
      lower, very bleeding rectal tumor, the macroscopically characters evoking quite
      sure a malignant neoplasm. Three successive histopathologically examinations
      remained inconclusive and only the fourth suggested the diagnosis of benign
      glandular polyp. That conclusion strongly contrasted with all the data obtained
      by the macroscopically examinations. Nevertheless the therapeutically option was
      in favor of a sphincter-saving surgery, the practiced operation being a pull
      through rectosigmoid resection (Babcock). Recovery of the patient which is in a
      good condition at present (two years after surgery). The histopathological
      examination of the operative specimen stipulated like diagnosis: rectal
      haemangioma with component parts of lymphangioma. Carrying on, the paper
      presented a review of the literature data referring to the very limited
      experience of others authors, regarding clinical aspects, diagnostics and
      therapeutically problems of the rectal haemangioma. In similar cases presenting
      voluminous rectal (or colonic) possibly benign tumors, haemangioma like,
      macroscopically diagnostic being difficult or unsure, but also without a
      certitude for a malignant tumor, it is recommended a sphincter-saving operation,
      adapted to the general status of the patient. In cases with malignant characters
      at the final histopathological examination, on the operative specimen, the
      transformation of the initial intervention in a amputation type surgery may be a
      possible alternative.

PMID- 9755577
TI  - [A voluminous hepatic hydatid cyst of the right lobe in a patient with
      hypertrophic liver cirrhosis--comments on a case].
AB  - There is presented the case of a patient with liver cirrhosis hepatomegalic form,
      echinococcosis and gallbladder stones. After the presentation of the clinical
      findings, there are discussed the problems of the surgical treatment. The
      remaining cavity was treated by pericysto-jejunostomy. The postoperative recovery
      was uneventful.

PMID- 9755578
TI  - [Myocardial revascularization interventions].
AB  - Elective coronary artery bypass surgery (CABG) can be performed with low
      operative mortality. There is a controversial discussion whether short- and long
      term results of CABG can justify this procedure even in elderly patients.
      MATERIAL AND METHODS: We retrospectively evaluated the clinical profile,
      operative procedure, postoperative short- and long-term results of 1127 patients
      over 70 years of age who underwent myocardial revascularization between January
      1985 and December 1996. RESULTS: Mean age was 73.9 years. In 1996,
      septuagenarians represented 21.5% of our operated coronary patients, when
      compared with 6.4% in 1985. Analysis of risk factors showed an increasing
      prevalence of renal failure, obesity, hyperuricemia and a history of smoking.
      Preoperatively 87% of our patients were in NYHA-class III and IV. The percentage
      of emergent operations decreased over the observed period by 10.3%. Internal
      mammary artery was used with increasing frequency (44.8% in 1985-92 vs. 61.5% in
      1993-96). The number of simultaneous valve replacements increased, too.
      Postoperatively, we noted rising incidence of respiratory failure (17.1%) and
      neurological disorders (13.7%). On the other hand, the need for intraaortic
      balloon pumping and hemofiltration declined by 6.6% and 2.9%. Perioperative
      mortality (< or = 24 h) was 3.65%, hospital mortality (< or = 30 days) was 9.64%.
      Actuarial 1 year at was 82% (+/- 4.3%), and 65.7% (+/- 3.8%) at 5 years.
      CONCLUSIONS: Our data suggest that CABG can be performed in septuagenarians with
      an acceptable operative risk. Since the large majority of patients improve
      symptomatically, surgery is the recommendable option for a growing number of
      elderly patients suffering from severe angina.

PMID- 9755579
TI  - [The place of laparoscopy in assessing and treating a pain syndrome of the right
      iliac fossa].
AB  - The study is considering a trial of 87 patients (61 women 17 and 76 years old)
      admitted in our clinic between 1995-1996. The preoperative diagnosis was
      coincident with the laparoscopic one in 10 cases the laparoscopic one in 10 cases
      the laparoscopy completed the diagnosis and in 12 cases it showed out other
      organ's disease, evicting useless operations. In the 87 patients we performed: 53
      appendectomies, 20 oophorectomies, 15 partial oophorectomies, 9 right
      adnexectomies, 2 adhesiolysis, 2 lymph node biopsies, 1 epiploic fringe excision
      for necrosis, 1 appendicular stump removal. The evolution was favourable in all
      patients, the mean postoperative hospitalization was 48 hours.

PMID- 9755580
TI  - [Total gastrectomy with mechanical sutures].
AB  - Between 1994-1996, nine consecutive patients underwent total gastrectomy with
      stapled sutures for II, III or IV TNM stage carcinoma (8 patients) or lymphoma (1
      patient) of the middle or upper stomach. Digestive continuity was established by
      stapled end-to-side "ended", end-to-side and end-to-end Roux-en-Y (7 patients)
      and omega loop (2 patients) esophagojejunal anastomoses using circular staplers
      (EEA or ILS). The duodenal stump and the end of the Roux loop were closed with TA
      55 or TA 30 linear stapler. Interjejunal anastomoses were hand sewn. Nasojejunal
      feeding catheter was placed for ten days in all patients. No postoperative
      mortality non anastomotic fistula occurred. One patient had duodenal stump
      leakage which closed spontaneously. In three patients postoperative chemotherapy
      with 5-FU and Leucovorian was associated. At late follow-up, there were two
      patients with reflux esophagitis cured by medical treatment and one patient with
      peritoneal and hepatic metastases at relaparotomy. In conclusion, the use of
      stapled sutures in total gastrectomy facilitates esophagojejunal anastomosis and
      improves suture reliability.

PMID- 9755581
TI  - [An iliac-mesenteric-atrial shunt in the Budd-Chiari syndrome with extensive
      thrombosis of the inferior vena cava].
AB  - A 34-year-old woman with no history of any liver diseases was admitted to the
      service for a Budd-Chiari syndrome and an extensive thrombosis of the inferior
      vena cava. The symptoms of the portal hypertension were present, with an enormous
      ascites, mild esophagogastric varices, associated with increased edema of the
      lower limbs, perineum and abdominal wall. The diagnosis was established by color
      Doppler ultrasonography, CT and cavography. An ilio-mesenterico-atrial shunt,
      between the right iliac vein, the superior mesenteric vein and the right atrium
      was successfully performed, transdiaphragmatically, by abdominally and right
      thoracic approach, using a 35 cm Dacron prosthesis. Postoperative evolution was
      very good. The color Doppler ultrasonography showed a good flow in the shunts.
      After 14 days ascites decreased over 70% and the inferior edema almost
      disappeared. 2 month later ascites decreased over 80%, the esophageal varices and
      edema disappeared completely. To our knowledge, this is the first case in the
      country, in which a patient underwent ilio-mesenterico-atrial shunt for Budd
      Chiari syndrome and inferior vena cava extensive thrombosis.

PMID- 9755582
TI  - [An endoscopic treatment alternative in vesico-ureteral reflux (VUR)].
AB  - Vesicoureteral reflux (VUR) represent an important pathology (surgical treatment
      was until recently the "gold standard" therapy) in urology. Between September
      1995 and October 1997 we used endoscopic Romanian collagen injection in 21 cases
      with VUR (3 cases grade II, 14 cases grade III, 4 cases grade IV). The collagen
      solution (1/1 with distilled water) was injected at the 6 hour of the ureteral
      large ostium (15/35 ml). In some cases we obtained the perfect occlusion of the
      incompetent ureteral ostium by complementary injections at 3 and 9 hours. It was
      necessary to reinject collagen twice in 8 cases and three times in 3 cases.
      Success rate appeared in 66.66% cases. We did not confront ourselves with
      postoperative complications. Hospitalization period was 3.2 days. The mean follow
      up period was 12 months (range 6 to 28). Our results prove that endoscopic
      collagen injection applied in VUR is a simple, efficient, without complications
      method, minimally invasive.

PMID- 9755583
TI  - [An endoscopic treatment method for postoperative stenoses].
AB  - The endoscopic procedures include a great variety of procedures for the treatment
      of the upper and lower gastrointestinal bleeding of the benign and malign
      jaundice, of the primary or secondary gastrointestinal strictures. The authors
      present the case of a patient with a postcaustic oesophageal stricture for whom
      the surgical treatment was an esogastroanastomosis. Quite early in the
      postoperative course the anastomosis got, very tight due to a anastomotic
      fistula, and we succeed to dilate it with endoscopic procedures.

PMID- 9755584
TI  - [Synthetic fabrics in reparative surgery of the abdominal wall].
AB  - Prosthesis use in surgical repair of abdominal wall is becoming nowadays a
      worldwide method, being imposed by its efficiency in solving the defects. The
      authors are speaking in the light of their experience gained with 100 patients
      that underwent the operation of prosthesis implant inside the abdominal wall
      between 1990 and 1996. There have been correlated the early and late
      postoperative results with some features of this surgical procedure (see below),
      to prove its efficacy. The authors discuss some principles of alloplastic
      treatment, which represent also the conclusions of the study: the moment of when
      a prosthesis is recommended, the choice of synthetic material, where and how is
      placed the prosthesis, some additional measures which contribute to therapeutic
      success.

PMID- 9755585
TI  - [The advantage of preparing the colon with Fortrans for diagnostic explorations
      or surgical interventions].

PMID- 9755586
TI  - Two endemic foci of heterophyids and other intestinal fluke infections in
      southern and western coastal areas in Korea.
AB  - Two endemic foci of heterophyid infections were discovered in coastal villages of
      Puan-gun, Chollabuk-do, and Sachon-gun. Kyongsangnam-do, Korea. Fecal
      examinations were performed on 153 inhabitants of Puan-gun and 138 of Sachon-gun,
      using cellophane thick smear and formalin-ether sedimentation technique. The
      helminth egg and/or protozoan cyst positive rate was 21.5% (33/153) in Puan-gun
      and 39.1% (54/138) in Sachon-gun. In Puan-gun, the egg positive rate of
      heterophyids was the highest, 17.6%, and that of other parasites was 0.7-2.6% by
      parasite species. In Sachon-gun, that of heterophyids was 18.8%, followed by
      Clonorchis sinensis (12.3%), and other parasites (0.7-5.0%). Twenth-two (Puan
      gun) and six (Sachon-gun) heterophyid egg positive cases were treated with
      praziquantel, and adult flukes were collected from their diarrheic stools. A
      total of 3,284 adult flukes of Heterophyes nocens was collected from all of the
      22 patients treated in Puan-gun (3-778 individually), and other trematodes were
      also collected from 2-15 patients: Pygidiopsis summa, Stellantchasmus falcalus.
      Metagonimus yokogawai, M. miyatai, Stictodora fuscata. Heterophyopsis continua,
      Acanthoparyphium kurogamo, and Gymnophalloides seoi. In Sachon-gun, M. yokogawai
      (3,007 specimens), H. nocens (120), and S. falcatus (46) were collected from 5 of
      6 treated patients, and H. continua and S. lari each from one patient. The
      present study revealed that heterophyid flukes, especially H. nocens and M.
      yokogawai, are prevalent in the southern and western coastal areas of Korea where
      fresh and/or brackish water fishes are popularly eaten raw.

PMID- 9755587
TI  - Discovery of Gymnophalloides seoi metacercariae in oysters from islands of the
      West Sea known as the habitats of paleartic oystercatchers.
AB  - An epidemiological survey was performed to know the infection status of oysters
      with Gymnophalloides seoi metacercariae in 7 islands of the West Sea known as the
      habitat of paleartic oystercatchers, Haematopus ostralegus osculans, in Korea.
      The surveyed areas were Aphaedo (Shinan-gun, Chollanam-do), Jangjado, Sonyudo and
      Munyodo (Okdo-myon, Kunsan-shi, Chollabuk-do), Yubudo (Changhang-up, Sochon-gun
      Chungchongnam-do), and Polumdo and Chumoondo (Sodo-myon, Kangwha-gun. Inchonshi).
      The oysters collected from Aphaedo, the known endemic focus, were examined
      monthly from August 1995 to October 1996 for observation of any seasonal
      variation of the metacercarial density. The average metacercarial burden was 761
      2,077 by month, but the seasonal variation of the metacercarial density was not
      obvious. A total of 54 metacercariae was detected in 63 oysters collected from
      Yubudo. Out of 30 oysters from Sonyudo, 25 (83.3%) were infected with 1-66
      metacercariae (12.6 in average). All of 50 oysters (100%) from Munyodo were
      infected with 3-162 metacercariae (53.5 in average). Only 4 metacercariae were
      detected in 100 oysters from Chumoondo. However, no metacercariae were found in
      55 oysters from Jangjado and 50 oysters from Polumdo. From the above results, it
      was confirmed that G. seoi is still highly prevalent in oysters from Aphaedo, and
      several islands of the West Sea known as the habitats of paleartic oystercatchers
      are new endemic areas of this fluke.

PMID- 9755588
TI  - Infection kinetics and developmental biology of Cryptosporidium muris (strain
      MCR) in Korean native kids and Corriedale lambs.
AB  - A total of nine Korean native kids and two Corriedale lambs, 1-20 days old, were
      each inoculated per os with a single dose of 2 x 10(7) oocysts of Cryptosporidium
      muris (strain MCR) originated from mice to elucidate the kinetics and
      developmental stages of the coccidium in small ruminants. Irrespective of host's
      age, the prepatent period for both animals ranged from 19 to 35 days (28.1 days,
      on the average) and the patent period 16-85 days (47.8 days), and the total
      oocyst outputs showed enormous differences. Infection with greater numbers of
      oocyst outputs was not ordinarily established by transmission experiments.
      Oocysts discharged from the kids retained their infectivity by the mouse
      titration method. The immunogenicity of the coccidium and oocyst reproduction
      were proven by challenge infection and administration of prednisolone acetate,
      respectively. All the developmental stages of the coccidium in parasitophorous
      vacuoles were found by transmission electron microscopy in the pits of the
      gastric glands of a kid inoculated with oocysts and then necropsied on day 44
      postinoculation. It indicated the full course of the host-parasite relationship
      in kids and lambs as well as mice.

PMID- 9755589
TI  - Immunodiagnosis of clonorchiasis using a recombinant antigen.
AB  - A cDNA expression library of Clonorchis sinensis adult worm was constructed, and
      screened out immunologically. One clone, pBCs31, was selected in view of its
      predominant reactivity with an experimentally infected rabbit serum. Recombinant
      C. sinensis antigen with 28 kDa as a beta-galactosidase fusion protein produced
      in Escherichia coli was identified by immunoblot analysis. The cloned gene was
      composed of 16 copies of a 30 base pair repeat and an additional 320 bases. The
      deduced amino acid sequence of the tandem repeat was AQPPKSGDGG. On RNA slot blot
      analysis. C. sinensis adult worm RNA showed a positive reaction with the cloned
      gene. Enzyme-linked immunosorbent assay using a purified recombinant antigen of
      pBCs31 showed high specificity for diagnosis of clonorchiasis.

PMID- 9755591
TI  - Neoplagioporus zacconis (Trematoda: Opecoelidae) from the intestine of the pale
      chub, Zacco platypus, in Korea.
AB  - Neoplagioporus zacconis (Yamaguti, 1934) (Trematoda: Opecoelidae) was found from
      the intestine of the pale chub, Zacco platypus, for the first time in Korea. The
      worms were characterized morphologically by oval body shape, bipartited seminal
      vesicle, sinistrally located genital pore, and lobed ovary, and distinguished
      from the two other species of Neoplagioporous by body shape and distribution of
      vitelline follicles. The morphological characteristics, except the ovary, well
      corresponded to those of the previous descriptions. The morphological difference
      of the ovary was considered as a character of geographical phenotypic variation.

PMID- 9755590
TI  - Changes in enzyme activity and expression of DHFR of Toxoplasma gondii by
      antifolates.
AB  - The responses to antifolates of Toxoplasma gondii were investigated by measuring
      the dihydrofolate reductase (DHFR) activity, quantity of DHFR mRNA, and single
      strand conformational polymorphism (SSCP) pattern. Pyrimethamine (PYM) and
      methotrexate (MTX) were tested as antifolates. When T. gondii was treated with
      PYM, the viability was decreased by the increasing concentration of PYM, DHFR
      activity tended to increase as the passage proceeded, and the quantity of mRNA
      expressed was also increased according to passages. The viability of T. gondii
      was decreased by the increasing concentration of MTX, but it was maintained over
      40% up to 100 microM MTX. DHFR activity was 77.4% in the 1st passage (1 microM).
      82.2% in the 4th passage (10 microM), and 141.3% in the 7th passage (100 microM).
      But no changes were detected in SSCP pattern of T. gondii exposed to PYM and MTX,
      both. These results suggested that the response of T. gondii to PYM was regulated
      by transcriptional level and that, in MTX, the viability of T. gondii was derived
      from increasing DHFR activity.

PMID- 9755592
TI  - Immunosuppressive effect of Cryptosporidium baileyi infection on vaccination
      against avian infectious bronchitis in chicks.
AB  - Two-day-old commercial chicks were inoculated orally with 2 x 10(6) oocysts of
      Cryptosporidium baileyi and vaccinated with 10(3.5) EID50/head of a commercially
      available avian infectious bronchitis (IB) live virus vaccine at 4 and 14 days
      following inoculation. Chicks infected with C. baileyi were shown to have an
      immunosuppressive effect on IB virus. It is concluded that infection with the
      protozoon in early life may increase their susceptibility to IB.

PMID- 9755593
TI  - Genetic variance of Trichomonas vaginalis isolates by Southern hybridization.
AB  - In the present study, genomic DNAs were purified from Korean isolates (KT8, KT6,
      KT-Kim and KT-Lee) and foreign strains (CDC85, IR78 and NYH 286) of Trichomonas
      vaginalis, and hybridized with a probe based on the repetitive sequence cloned
      from T. vaginalis to observe the genetic differences. By Southern hybridization,
      all isolates of T. vaginalis except the NYH286 strain had 11 bands. Therefore all
      isolates examined were distinguishable into 3 groups according to their banding
      patterns; i) KT8, KT6 and KT-Kim isolates had 11 identical bands such as 1 kb,
      1.2 kb, 1.6 kb, 1.9 kb, 2.3 kb, 2.7 kb, 3.2 kb, 3.4 kb, 3.8 kb, 4.9 kb and 6.0
      kb. ii) The metronidazole-resistant IR78 strain had the same bands as KT-Lee
      isolate at bands of 1 kb, 1.2 kb, 1.6 kb, 1.8 kb, 2.1 kb, 2.5 kb, 2.7 kb, 2.9 kb,
      3.4 kb, 5.0 kb and 6.0 kb. Bands of CDC85, metronidazole-resistant strain, were
      similar to those of IR78 and KT-Lee, except that 3.2 kb replaced 2.9 kb. iii)
      NYH286 particularly had 12 bands and band patterns were similar to IR78 with a
      few exceptions as follows: i) 6.2 kb in place of 6.0 kb, ii) 2.0 kb and 2.2 kb
      instead of 2.1 kb. Through the results obtained, genetic variance of T. vaginalis
      isolates was demonstrated by Southern hybridization.

PMID- 9755594
TI  - Biological roles of vascular endothelial cell in various pathologic processes.

PMID- 9755595
TI  - [Effect of phenylephrine, endothelin and angiotensin II on reperfusion
      arrhythmias. A role for Na+/H+ exchanger activation via protein kinase C].
AB  - Stimulation of receptors for alpha 1-adrenergic agonist, endothelin (ET) and
      angiotensin II (AT) activates the cardiac sarcolemmal Na+/H+ exchanger (NHE),
      perhaps via protein kinase C(PKC)-mediated pathway(s). We tested for the ability
      of these extracellular stimuli to exacerbate reperfusion arrhythmias and for the
      possible role of NHE activation and PKC in such phenomena. Isolated rat hearts (n
      = 12/group) were subjected to dual coronary perfusion. After 15 min of aerobic
      perfusion, flow to the left coronary bed was reduced to 5% of basal values for 12
      min, and the same bed was then reperfused for 5 min. An alpha 1-adrenergic
      agonist phenylephrine (PE) at 1 or 10 mumol/L, ET at 0.5 or 5nmol/L or AT at 1 or
      10mumol/L was infused selectively into the left coronary bed during 12 min of
      regional low flow ischemia. The incidence of reperfusion-induced ventricular
      fibrillation (VF) was increased from 17% in control to 33% and 75%* with 1 and 10
      mumol/L PE(*p < 0.05 vs control) from 8% in control to 8% and 12% with 0.5 and 5
      nmol/L of ET. However, AT had no effect. The selective NHE inhibitor NOE642 at 1
      mumol/L, infused concomitantly with 10 mumol/L PE, reversed the proarrhythmic
      effects of PE; VF incidence was reduced from 67% to 8%*. However, glibenclamide
      (a blocker for the ATP-sensitive K+ channel) at 1 mumol/L did not affect the
      proarrhythmic effects of PE. Infusion of a specific PKC inhibitor GF109203X(GF)
      at 30 or 300 nmol/L, starting from 5 min before ischemia and maintained
      throughout ischemia concomitantly with 10 mumol/L of PE, was partially effective
      in reducing VF incidence; which reduced from 75% in control to 42% with 300
      nmol/L of GF. These results suggest that, in rat hearts subjected to regional low
      flow ischemia and reperfusion, stimulation of alpha 1-adrenergic receptor can
      exacerbate reperfusion-induced VF, whose mechanism(s) may involve NHE activation.
      Moreover, PKC activation does not appear to be the sole signaling mechanism for
      this phenomenon.

PMID- 9755597
TI  - Role of dorsal neck proprioceptive inputs to vestibular compensation in humans.
AB  - To investigate the role of cervical proprioceptive inputs in the process of
      vestibular compensation, we performed static posturography in patients with acute
      and compensated unilateral vestibular dysfunction, by applying vibratory
      stimulation to the dorsal neck muscles. Neck vibration induced disequilibrium in
      both groups of patients, but was more pronounced in the compensated patients.
      These results indicate that manipulation of the neck afferents causes
      discompensation in subjects whose vestibular dysfunction has already been
      compensated by multisensory inputs including neck afferents.

PMID- 9755596
TI  - Effects of serum of streptozotocin-induced diabetic rats on vascular smooth
      muscle cell growth in vitro.
AB  - This study was undertaken to biochemically and immunohistochemically clarify the
      expression of basic fibroblast growth factor (bFGF), insulin-like growth factor-I
      (IGF-I), fibroblast growth factor receptor (bFGFR), insulin-like growth factor-I
      receptor (IGF-IR) and vascular smooth muscle cell (VSMC) growth by using
      Streptozotocin (STZ) treated rat serum. At 12, 16, 24 weeks after STZ
      administration, blood sera were collected from STZ treated rats. STZ treated rat
      sera promoted much more vascular smooth muscle cel proliferation than control
      sera. IGF-I was increased in the sera of STZ treated rats. Also according to
      western blot analysis, the protein synthesis of bFGFR and IGF-IR in the VSMCs was
      increased in STZ treated rat sera. Immunohistochemically, bFGF, IGF-I and their
      receptors were much more localized in VSMCs in STZ treated rat sera than in
      control sera. These results suggest that the growth factors and their receptors
      produced in VSMCs in STZ treated rat serum may contribute to the proliferation of
      VSMCs in autocrine and paracrine patterns.

PMID- 9755598
TI  - Veins of the lumbar spinal ganglia in human adults and fetuses.
AB  - To obtain a fundamental knowledge of the morphological relationship between nerve
      root symptoms and circulatory disorders, the distribution pattern of the veins in
      the lumbar spinal ganglia from the first to fifth vertebrae was investigated in 5
      adult human cadavers (mean age 69.6 years) and 5 human fetuses (mean age 6.6
      months). The following results were obtained: 1) In the adults the veins
      perforating from the outer surface of the fifth lumbar spinal ganglion were
      smaller in number than those perforating from the first to fourth ganglia. In
      contrast, in the fetuses the number of such veins was increased in the lower
      lumbar spinal ganglia. In each of the ganglia, the number of veins emerging
      through the dorsal side was much higher than the number perforating from the
      outer surface of the ventral sides. The veins perforating through the outer
      surface of the ganglion formed weak venous networks (periganglionic venous
      plexus) surrounding the dorsal ramus of the spinal nerve. 2) The veins
      communicating with the tributaries from the periganglionic venous plexus were
      classified into three types. Type 1 veins flowed into the intervertebral veins
      (the frequency ranged from 9.2 to 18.2 in the adults and from 22.4 to 37.0 in the
      fetuses). Type 2 veins coursed in the spinal cord along the dorsal root fibers
      and penetrated the dura mater on the way (the frequency ranged from 0.4 to 4.8 in
      the adults and from 1.2 to 2.2 in the fetuses). Type 3 veins opened directly into
      the internal vertebral plexus (the frequency ranged from 0.4 to 1.8 in the adults
      and from 0 to 0.4 in the fetuses). Type 1 veins were the most frequent among the
      three types of veins in both adults and fetuses. Few type 3 veins were observed
      in either group. 3) In the first and second lumbar vertebrae in the adults, three
      quarters of each spinal ganglion was situated in the vertebral canal. In the
      lower lumbar region (L3-L5), three quarters of each spinal ganglion lay on the
      outside of the vertebral canal. In the fetuses, approximately one half to three
      quarters of each lumbar spinal ganglion was located in the vertebral canal.

PMID- 9755599
TI  - Combination of low back pain and previous low back pain and shoulder stiffness in
      construction employees.
AB  - A postal questionnaire for the prevalence of low back pain was studied with
      relevance to stiffness of that shoulder and a history of low back disorders in
      construction employees. The percentage of clerical employees with low back pain
      was 31.3% and of field workers was 30.3%. Odds ratios representing a relative
      risk factor for low back pain relating to each age group showed 2.35 in the
      clerical and 2.10 in the field workers at the age of 30-34 years, and 3.34 and
      2.58 at the age of 35-39 years, respectively. In the persons with positive
      previous low back pain, the prevalence rate of low back pain was 52.6% in the
      clerical, and 50.2% in the field workers. Odds ratios for low back pain relating
      to previous low back pain significantly exceeded unity for the clerical employees
      (OR = 9.53) and the field workers (OR = 10.28), compared to those without a
      history of previous low back pain. The incidence of stiffness of the shoulder was
      48.2% in the clerical and 45.2% in the field workers, and the prevalence rate of
      low back pain among those with stiffness of the shoulder was 68.5% in the
      clerical and 65.8% in the field workers. Odds ratio were 3.03 in both groups.
      Among each age group, the prevalence rate of stiffness of the shoulder with low
      back pain increased gradually to a maximum in the 45-49 age group of 19%, and
      then dropped. In those with a history of low back pain and/or stiffness of the
      shoulder, the prevalence of low back pain showed significantly greater value than
      other risk factors.

PMID- 9755600
TI  - Successful treatment of anomalous origin of the left coronary artery from the
      pulmonary artery in a 5-week-old male infant.
AB  - A 5-week-old male infant who was referred to our hospital because of tachypnea
      and poor feeding. An electrocardiogram showed a deep Q wave in lead aVL, negative
      T waves in leads I, II, III, aVF and V6 and a positive T wave in VL.
      Echocardiography revealed severely impaired left ventricular function.
      Aortography confirmed with a diagnosis of anomalous origin of the left coronary
      artery from the pulmonary artery (ALCAPA). Takeuchi's procedure was performed and
      the patient maintained postoperatively on assisted circulation for 7 hours even
      though sternal closure delayed until 7 days post operatively. His left
      ventricular function showed and marked improvement gradually.

PMID- 9755601
TI  - Treatment of posterior skull base tumors.
AB  - Surgery for posterior skull base tumors may be associated with high morbidity and
      mortality because of the complex anatomy, irregular bony topography, and vital
      neurovascular structures in this region. We experienced three benign posterior
      skull base tumors. These were petroclival and foramen magnum meningiomas and a
      jugular formen neurinoma. Three dimensional computed tomography (3 D-CT) in
      addition to the conventional CT, magnetic resonance imaging (MRI), and cerebral
      angiography were performed preoperatively. Preoperative embolizations for the
      tumors were also done, and intraoperative neurophysiological monitorings were
      performed. The tumors could be subtotally removed with no damage to the
      brainstem, cranial nerves, and vessels. No newly developed postoperative
      neurological symptoms were observed. As to the remaining tumors, gamma knife
      (gamma-knife) therapy was planned. 3 D-CT was very useful in the preoperative
      evaluation of the surgical approach, and the intraoperative neurophysiological
      monitoring was considered to be necessary to prevent permanent damage. gamma
      knife after direct approach was recommended for the benign posterior skull base
      tumors.

PMID- 9755602
TI  - [Endocrine surgery. Diagnosis and therapy for thyroid malignant lymphoma].

PMID- 9755603
TI  - [Osteoporosis and the prevention of age-related fractures].

PMID- 9755604
TI  - [Removal of bile duct stones by endoscopic papillary balloon dilatation (EPBD) of
      papilla of Vater].

PMID- 9755605
TI  - [A case of bilateral paramedian thalamic infarct syndrome that presented with
      consciousness disturbance and vertical gaze palsy].

PMID- 9755606
TI  - [The basic concepts of public health].

PMID- 9755607
TI  - [Health from human ecology view point].

PMID- 9755608
TI  - [Home care service utilization by severely mentally and physically handicapped
      persons].
AB  - PURPOSE: To investigate the utilization of in-home services by severely mentally
      and physically handicapped persons at home in order to clarify the vital factors
      associated with the services. METHODS: Questionnaires were delivered to 174
      severely mentally and physically handicapped persons who were registered with 8
      institutions in Tokyo and Kanagawa prefecture through each institution. One
      hundred and thirteen respondents among them were the subjects of this study. As a
      conceptual model Andersen's model was adopted. RESULTS: (1) The age of subjects
      varied from 2 to 50. There were no subjects between the age of 7 to 17. The mean
      functional handicap severity score (SCORE) was 5.8 +/- 8.4 standard deviation.
      Ninety seven percent of main caregivers were mothers, even among the aged. (2)
      Over 1/2 of the subjects reported having utilized institutional services. On the
      other hand the percentage for visiting nurse service (VNS) and home help services
      were 28.3% and 7.7% respectively. (3) Subject who used V.N.S. had significantly
      higher SCORES and higher luck of health of caregivers. Caregivers utilized V.N.S.
      as a substitute to reduce their burden in activities care at home. On the other
      hand, users of institutional services showed high scores in difficulties with
      daily help and perceived difficulties with medical treatments: it showed that
      they sought institutional care to reduce there careburden. (4) Total number of
      used by each client for in-home service was explained only by both difficulties
      of daily help and SCORE from multiple regression analysis. CONCLUSION: Users of
      visiting nursing service expect highquality care based on current medical
      knowledge and also with the aim of caregiver's health. With the increasing age of
      caregivers it appears to be important to enhance visiting nurse services, reduce
      the caregiver burden, and provide active support of home care for the
      handicapped.

PMID- 9755609
TI  - [Factors influencing grief due to bereavement among elderly widows and widowers].
AB  - OBJECTIVES: To identify the factors that influence the grief of bereaved elderly
      people due to the death of a spouse. METHOD: Subjects consisted of 172 widows and
      widowers (137 females, 35 males) aged 60 or older who experienced bereavement of
      a spouse in the last three years. Between August 1994 and October 1996, the
      subjects were interviewed using a semi-structured questionnaire and data was also
      obtained from self-report measures which were returned by mail. A questionnaire
      consisting of 26 items was prepared based on the theories of Parkes and Deeken.
      These responses were classified into 4 categories (sensory paralysis, deep
      attachment and protest, disintegration, reconstruction) and analysis was made by
      these categories. The time course of the grief was evaluated at 1 week, 49 days
      and 1 year after the death of the spouse and the time of survey. RESULTS: (1) Of
      the 172 subjects, general health was graded as poor or slightly poor in 33.6%,
      67.4% cared for their spouse during medical treatment; and the average GDS
      depression score was 5.85 (SD = 3.50). (2) With respect to anticipated grief,
      while their spouses were under medical treatment, more than 50% of the subjects
      were thinking "I will do Whatever I can to cope". (3) Change in grief response
      over time: For "sensory paralysis", "I have done whatever I can" rated the
      highest at 3 points or more on a scale of 4, from immediately after the spouse's
      death to the present. For "deep attachment and protest", deep attachment
      including "always thinking of the lost one" marked higher (3.4 points immediately
      after death to 2.9 at present) than protest. For "disintegration", "nobody
      understands what I feel" rated the highest (2.6-2.9 points). For
      "reconstruction", the subjects gradually accepted the death as "unavoidable" and
      had started to adapt. (4) Factors that significantly influenced grief were the
      subject's health condition, whether the subject had been notified of the name of
      the disease or given a prognosis; whether subject provided care for the spouse
      and GDS depression score. CONCLUSION: Sufficient anticipated grief resulted in a
      feeling of achievement in the sensory paralysis aspect of the grief response and
      in a long lasting feeling of deep attachment as loneliness and solitude.
      Disintegration was largely related to depression according to GDS score. Grief
      was less deeply felt when the subject was healthy, had been informed of the name
      of the spouse's disease, and had cared for the spouse during medical treatment
      before bereavement.

PMID- 9755610
TI  - [Geographical distribution of medical expenditure for the aged insured by
      National Health Insurance in secondary medical care areas in Japan].
AB  - PURPOSES: To determine what factors affect medical expenditure for the aged
      insured by the National Health Insurance among secondary medical care areas.
      METHOD: The original data of municipalities were combined and converted into the
      data of secondary medical areas. The original data included medical expenditure
      of the aged in 1994, medical supply factors per 100,000 population (numbers of
      doctors, numbers of general beds in hospitals, numbers of clinics, etc.) and
      socio-economic factors (income, proportion of employees for three sectors of
      industries, population density, average size of family, etc.). Medical
      expenditures for inpatients and outpatients were used separately as independent
      variables. The medical supply and socio-economic factors have been used as
      dependent variables. Multiple regression models were applied to clarify the
      differences in the contributing factors between inpatient and outpatient.
      RESULTS: 1. The maximum inpatient and outpatient medical expenditures for the
      aged are respectively 4 times and 2.6 times more expensive than minimum
      expenditures among secondary medical care areas. 2. The numbers of beds, income
      per capita, numbers of doctor, average size of family, proportion of employees
      for third level industry and income accounted for 57.4% of variance in inpatient
      medical expenditure of the aged. 3. The proportion of employees for first level
      industry, the numbers of beds and average members of family accounted for 21.4%
      of variance in outpatient medical expenditure of the aged. 4. Medical expenditure
      for inpatients related with medical supply and socioeconomic factors differently
      from that of outpatients.

PMID- 9755611
TI  - [The relation between platelet aggregation and constitutional and lifestyle
      variables in two Japanese communities].
AB  - To investigate the contribution of the platelet aggregation in the development of
      cardiovascular diseases, we examined the relation of constitutional and lifestyle
      variables with platelet aggregation for a total of 306 males aged 50 to 70 in
      Ikawa town, Akita prefecture (n = 163) and Noichi town, Kochi prefecture (n =
      143). The examination of platelet aggregation was completed within 3 hours of
      obtaining blood samples. We used ADP (Adenosine 5'-diphosphate) as an agonist and
      obtained PATI (the platelet aggregatory threshold index) by nephelometry.
      Platelet count, mean platelet volume, white blood cell count, serum fatty acid
      compositions were also examined and dietary intake of fish, seafood and soy bean
      foods were inquired using one-week dietary records. PATI indicated a logarithmic
      normal distribution in both Ikawa and Noichi. The mean of logarithmic transformed
      PATI (log PATI) was higher in Ikawa than in Noichi. Thus platelet aggregation was
      lower in Ikawa than in Noichi. According to multiple regression analysis, age,
      platelet count in platelet rich plasma, mean platelet volume in platelet rich
      plasma, and white blood cell count were inversely associated with log PATI. Serum
      arachidonic acid composition tended to be inversely related with log PATI. Serum
      n3-polyunsaturated fatty acid composition was positively related with log PATI,
      and log gamma-GTP tended to be positively associated with log PATI. Soy protein
      intake and cigarette smoking showed no consistent associations with log PATI.
      This cross-sectional study suggests that serum n3-polyunsaturated fatty acid, and
      gamma-GTP, as an index of alcohol intake, reduce platelet aggregation while age,
      white blood cell count, platelet count, mean platelet volume, and serum
      arachidonic acid raise platelet aggregation.

PMID- 9755612
TI  - [Survival and disability in stroke by stroke subtype based on computed
      tomographic findings in three rural Japanese communities].
AB  - PURPOSE: We conducted an epidemiological study of survival and disability in
      stroke in three Japanese communities to seek community strategies for improvement
      in survival and disability. METHODS: A total of 297 first-ever strokes were
      identified between 1988 and 1992 in three rural communities (total population =
      47,000) located in Akita and Ibaraki. We analyzed survival rates and activity of
      daily living by sex, age-group and stroke subtypes. Successful review of computed
      tomography (CT) for 84 percent of the strokes (249 out of 297) was possible and
      the data were used for subtype analyses. RESULTS: For all strokes (n = 297)
      survival rates were 85% for 30 day, 70% for one year, 62% for three year. The
      rates tended to be lower in women than in men. The rates were lowest in ages less
      than 60 at thirty day, and in ages 80 and older at the end of the first and third
      year. Intracerebral hemorrhage with ventricular rupture, subarachnoid hemorrhage
      and cortical cerebral infarction had lower survival rates than intracerebral
      hemorrhage without ventricular rupture and lacunar infarction. Based on Cox's
      proportional hazard model, risk ratio for death was 2.07 in ages 70-79, and 3.80
      in ages 80 and older compared with ages 60-69. The risk ratio was 3.46 for
      intracerebral hemorrhage with ventricular rupture, 3.38 for subarachnoid
      hemorrhage and 2.46 for cortical cerebral infarction compared with lacunar
      infarction. The proportion of stroke survivors who need assistance from others in
      the first and third years tended to be higher in women than in men. The
      proportion was higher in older patients than in the younger, and higher for
      intracerebral hemorrhage with ventricular rupture and cortical cerebral
      infarction than in other subtypes of stroke. From logistic regression analysis,
      the odds ratio for disability in the first year was 6.55 for ages 80 and older
      compared with ages 60-69. The odds ratio was 5.61 for intracerebral hemorrhage
      with ventricular rupture, 4.53 for cortical cerebral infarction compared with
      lacunar infarction. In the third year the odds ratio was significant for ages 70
      79, and decreased for intracerebral hemorrhage with ventricular rupture (odds
      ratio = 2.98), and increased for cortical cerebral infarction (odds ratio =
      6.06). CONCLUSIONS: Survival and disability in stroke depended on age and stroke
      subtypes. Even after age adjustment, stroke subtypes with large cerebral
      involvement had worse prognosis than stroke subtypes. Community-based
      hypertension control programs are important to prevent any subtypes of stroke.
      Stroke subtypes as well as age should be taken into account to develop effective
      care and medical treatments for strokes.

PMID- 9755613
TI  - [Postpartum depression and social support].
AB  - OBJECTIVES: To ascertain the state of a mother's depression three months after
      childbirth and to what sort of or to whose social support it is related. METHOD:
      In October 1993, a questionnaire survey was conducted on the attributes, state of
      depression by Zung Self-rating Depression Scale, and social support of 300
      mothers who received health examinations of their 3 to 4 months' old infants at
      five health centers in Tokyo. Relationship between depression and social support
      of 256 mothers (rate of valid answer 85.3%) was examined by one-way analysis of
      variance, Pearson's product moment correlation coefficient and multiple
      regression analysis. RESULTS: The depression score averaged 37.3 points, with 73
      persons (28.5%) scoring 40 to 47 points (light) and 27 persons (10.5%) scoring 48
      or more points (medium level or higher). The following were the variables which
      individually showed a significant relationship to the depression score after
      controlling for age, education, number of children, type of family, and whether
      or not the mother was working: The emotional support score from the husband and
      his parents, such as the frequency in which the husband "listened to the mother's
      worries and anxieties" "was attentive or considerate to the mother" and "helped
      in feeding the child", the frequency in which the husband's parents "could be
      consulted on worries the mother had about childbirth, child care and child
      development" and "nursed and played with the child". It was found that the better
      the state of such support, the less the state of depression. On the other hand,
      support from the mother's parents, neighbors, and friends had no bearing on
      depression. CONCLUSION: The level of depression of the surveyed group was the
      same as that of the general female public. Postpartum depression was related to
      emotional support from the husband and emotional and practical support from the
      husband's parents. Therefore, from the aspect of preventing depression, we
      believe it is important that, firstly, the mother and family should understand
      the importance of support and improve the support by the family, and, secondly,
      the mother herself should improve her ability to cope.

PMID- 9755614
TI  - [Combination care of a patient with Joseph's disease local community].

PMID- 9755615
TI  - [Primary health care in Thailand with community participation special reference
      to Japanese assistance].
AB  - The international health cooperation of Japan for developing countries has been
      mostly concentrated on matters such as improvement of hygienic environment,
      prevention of tropical infectious diseases, establishment of hospitals with
      modern medical instruments and devices, and dispatch of medical experts. PHC
      (Primary Health Care) activities based on voluntary participation of local
      inhabitants in developing countries have been largely neglected. In the field of
      health and medical care, sufficient effect may not be achieved unless the local
      health activity is based on voluntary participation of the inhabitants. The
      introduction of highly advanced modern medical techniques may be beneficial to
      some of the inhabitants, while most of the local inhabitants may not have the
      chance to receive such benefits, and additionally it is difficult to propagate
      modern medical care and technique widely to rural areas in Thailand. In Thailand,
      PHC activity based on community participation was started in 1985, with the
      following three items as main themes: (1) Training of Village Health Volunteers
      (VHV) and Village Health Communicators (VHC), and development of their
      activities. (2) Establishment and operation of Health Centers. (3) Establishment
      and operation of Drug Cooperative System (DC). Earlier, as one of PHC activities
      developed by Japan, "Thailand Local Health Activity Improvement Project" based on
      the program of Thailand-Japan Partnership was initiated in 1976 in rural areas of
      Chanthaburi Prefecture. From 1982, third country training programs have been
      carried out by Japan International Cooperation Agency (JICA). Since 10 years have
      elapsed the initiation of PHC activity in rural areas in Thailand under the
      cooperation of the Governments of Thailand and Japan, it seems to be time to
      reconsider and study again how PHC activity should be developed in future based
      on candid evaluation of achievements and results.

PMID- 9755616
TI  - [Physician demand projection models in U.S.A].

PMID- 9755617
TI  - [Salt intake in young children].
AB  - Among adult Finns salt intake is about twice as high as the recommended levels
      and almost five-fold greater than the physiological requirement. Information as
      to salt intake in children has hitherto been sparse. Daily sodium intake among 1
      5-year-olds was investigated in this study, and the foodstuffs from which it was
      derived were identified. In all age groups, sodium intake was at least two-fold
      greater than the Nordic recommendations, and among five-year-olds it exceeded the
      recommended intake for adults. Approximately half of the sodium intake was found
      to have derived from salt used in cooking. Levels of sodium derived by children
      from dairy, meat and grain products were also relatively high. Sodium intake in
      children after infancy merits greater attention than previously accorded it, as
      permanent eating habits and taste preferences are already formed at this age, and
      reasonable limits for salt intake should therefore be established during
      childhood.

PMID- 9755618
TI  - [PET as a tool in pharmacologic development].
AB  - Positron emission tomography (PET) allows the in vivo recording of tracer
      compounds with respect to anatomical distribution, time course and absolute
      concentration. These features has proven of great value in drug development,
      especially in the phase of early clinical trials. PET can be used to assess the
      tissue kinetics of a new drug, or to evaluate a drugs interaction with a target
      system and thereby aid in decisions regarding dosing regimes.

PMID- 9755619
TI  - [Back pain--from the viewpoint of medical technology. Danish National Board of
      Health].
AB  - The appearance of various consensus reports, guidelines, Cochrane Centers, and
      other evidence-based medicine initiatives during the past decade has resulted in
      marked improvement in the rational utilisation of available knowledge of
      attitudes toward the issue of low back pain (LBP). Moreover, owing to the ready
      access to updated data bases, this knowledge has been disseminated with
      incredible speed. In the spring of 1995, the Danish National Board of Health in
      Denmark convinced a multidisciplinary team of back specialists to tailor data
      available in the international reports for Danish needs. The article outlines the
      findings of this team, the major recommendations being that providing information
      is preferable to treatment, that patients should be encouraged to remain active,
      that physical exercise should be kept up except during the acute phases, that
      most episodes of LBP are to be considered life events rather than automatic
      reasons to seek treatment, and that passive treatment should be minimised, though
      manipulation may be helpful in the short term.

PMID- 9755620
TI  - [Sciatica--diagnosis and surgical management].
AB  - Sciatica (a term used synonymously with lumbar radiculopathy) is usually caused
      by lumbar disc herniation or lumbar spinal stenosis. Mechanical compression of
      nerve roots is a predominant factor, and decompression the surgical goal.
      Emphasis should be placed on clinical identification of the nerve roots causing
      the complaint. Although computed tomography (CT) and magnetic resonance imaging
      (MRI) are the most important diagnostic tools used today, plain x-ray may be
      required for correct identification of the lowest mobile segment, and the
      functional myelography combined with CT may be required if lumbar spinal stenosis
      is suspected, or if the clinical findings are unclear--especially if the patient
      has already undergone surgery for sciatica. The proper selection for candidates
      for surgery seems to be a more important determinant of successful outcome than
      whether macro- or micro-surgery is used, or whether one or more segments are
      operated upon (12, 13). Clear clinical identification of the roots affected and
      corresponding pathological findings at imaging are the best predictors of
      successful surgical outcome, an additional factor of positive predictive value
      being psychosocial stability. Impaired fibrinolysis, occurring in smokers and in
      the sedentary and obese, may be a negative predictive factor (10, 11). Published
      findings suggest that, unlike the case with disc surgery (9), neither long
      duration of symptoms nor long preoperative sick leave is associated with poor
      outcome of surgery for spinal stenosis (14).

PMID- 9755621
TI  - [Back pain. Experimental studies are successful].
AB  - Recent experimental studies performed at the Dept of Orthopaedics at Gothenburg
      University have systematically assessed the basic pathophysiological mechanisms
      behind sciatica due to disc herniation. It has hereby been seen that the epidural
      presence of nucleus pulposus may induce structural and functional injury of the
      adjacent nerve roots similar in magnitude to those induced by mechanical
      deformation. By increasing the knowledge of the substances and mechanisms leading
      to this nucleus pulposus-induced nerve injury it may be assumed that sciatica to
      a certain extent may be treated by specific pharmacologic agents in the future,
      in combination with existing treatment modalities.

PMID- 9755622
TI  - [Decentralized special training in pulmonary medicine. A project using
      telemedicine].
AB  - In arctic Norway, where there is a lack of specialists in pulmonary medicine two
      postgraduate students, already qualified as specialists in internal medicine at
      Tromso Regional Hospital, applied to continue their training at their respective
      local hospitals. The regional hospital in Tromso has a long tradition of
      telemedicine, with network links to local hospitals in the region, and is
      equipped for interactive consultation and the bilateral transmission of x-rays
      and video recordings, and digital transmission of x-rays. Accordingly, supported
      by their supervisor, the two postgraduate students applied to the committee for
      postgraduate education in pulmonary medicine to have a year's work at their
      respective local hospitals, supervised via the telemedicine facilities, accepted
      as equivalent to a six-month module of the normal syllabus. The project was
      approved and executed as planned. The registrars, who were responsible for
      pulmonary service at their local hospitals, served four days a month at the
      regional hospital, and their supervisor visited the local hospitals one day each
      month. All internal education at the regional hospital was made available by
      means of a weekly interactive televised link-up, x-rays being displayed on screen
      as transmitted digitally; bronchoscopies were shown by video, and ad hoc
      tutorials arranged as needed. Evaluated by the national committee, the project
      was found satisfactory, and the registrars were duly qualified.

PMID- 9755623
TI  - [Decisions about life and death. An empirical study of the position of Danish
      physicians concerning end-of-life decisions].
AB  - In a postal questionnaire investigation of experiences and attitudes concerning
      end-of-life decisions among Danish physicians, most of the respondents reported
      having made decisions involving the hastening of a patient's death, and
      considered this acceptable. Such decisions were more frequent, and were
      considered ethically more acceptable, when made with the patient's informed
      consent than without. Of the respondents, two per cent had participated in
      assisted suicide, and five per cent had administered a lethal injection at the
      patient's request, practices considered ethically acceptable by 37 per cent and
      34 per cent, respectively, of the respondents. The most frequently cited reasons
      for opposing such practices were double effect principle, the active
      killing/allowed-death distinction, and the sanctity of life; and the most
      frequently cited justifications were respect for the patient's autonomy, the
      avoidance of unnecessary suffering, and the patient's right to a death with
      dignity.

PMID- 9755624
TI  - [Feto-maternal transfusion following cordocentesis].
AB  - Invasive intrauterine diagnostic procedures may be followed by feto-maternal
      transfusion. The authors studied the feto-maternal transfusion after
      cordocentesis. 199 women underwent fetal umbilical cord blood sampling for fetal
      karyotyping in weeks 15-26. Maternal serum alpha-fetoprotein level was measured
      before and after the procedure. The data were statistically analysed by multiple
      regression analysis and the paired and unpaired Student's t-tests. Twenty percent
      of more maternal serum alpha-fetoprotein level increase was observed in 73
      (36.7%) women. Maximum feto-maternal transfusion was 0.684 ml. The average feto
      maternal transfusion was 0.045 ml. No fetal exsanguination was observed. Positive
      correlation was found between bleeding time after cordocentesis (p = 0.0171) and
      feto-maternal transfusion as well as the duration of the procedure (p = 0.0275)
      and feto-maternal transfusion. Negative correlation was found between the amount
      of fetal blood sample and feto-maternal transfusion (p = 0.0431). The puncture
      site also influenced feto-maternal transfusion. If the cordocentesis has been
      performed at the insertion of the cord the feto-maternal transfusion was less
      than at the free floating umbilical cord (p = 0.0293). Higher feto-maternal
      transfusion was seen more often after transplacental cordocentesis (p = 0.002).
      These data suggest that fetomaternal transfusion in the indicator of the
      difficulty of the procedure.

PMID- 9755625
TI  - [Food allergy in patients with respiratory allergy. Diagnostic possibilities and
      problems].
AB  - In the past two years the authors examined 28 patients with abdominal complaints
      and allergic respiratory symptoms. Detailed internal, gastroenterological,
      allergological examinations were made. METHODS: 1 skin Prick-test (SPT) with
      inhalative and nutritive panel 2. measuring of food-specific (gliadin, alpha
      lactalbumin beta-lactoglobulin, ovalbumin) IgG-antibody level detecting with
      ELISA method, 3. leukocyte migration inhibition (LMI) test against the same
      foodstuffs, 4. histological examination of the stomach and the duodenum
      especially for mucosal mastocytes (MMCs). RESULTS: 1. SPT was positive in 23/28
      patients for inhalative, but in the 5 cases we did not identify any inhalative
      allergen. The SPT for the main foodstuffs were positive in 18 patients while in 3
      other patients there was urtica only for the other antigens. 2. The food-specific
      IgG-antibody level was increased in 18/27 patients against one or more antigens.
      The SPTs and the antibody determination showed identity in 8/18 cases. 3. The LMI
      tests were positive against one or more main food-products in 23/27 cases. There
      was common positivity in respect of antigens (between LMI test and antibody
      identification) in 17 cases. Pathological immunological reactions were presented
      against the same main foodstuffs with at least two methods for flour in 11, for
      egg in 10 and for milk in 12 patients. Endoscopic examinations were performed in
      27 cases. The number of the MMCs were increased in 22/27 patients. After a
      specific elimination diet open-food challenges were performed and they confirmed
      the results of the in vitro and in vivo examinations. CONCLUSION: It is common
      that the respiratory allergic symptoms in atopic patients accompanied with food
      allergy for the main foodstuffs caused not only more severe respiratory symptoms,
      but abdominal complaints too. In respect to the many positive LMI tests the late
      type hypersensitivity have important pathogenetical role in it. This three
      methods together define well the main food-products, which can be antigens as
      well. The examination of the MMCs supports the local disturbance in the
      immunoregulatory system.

PMID- 9755626
TI  - [Iodine deficiency in cardiovascular diseases].
AB  - The thyroid hormone deficiency on cardiovascular function can be characterized
      with decreased myocardial contractility and increased peripheral vascular
      resistance as well as with the changes in lipid metabolism. 42 patients with
      cardiovascular disease (mean age 65 +/- 13 yr, 16 males) were investigated if
      iodine insufficiency can play a role as a risk factor for the cardiovascular
      diseases. The patients were divided in 5 subgroups on the ground of the presence
      of hypertension, congestive heart failure, cardiomyopathy, coronary disfunction
      and arrhythmia. Urine iodine concentration (5.29 +/- 4.52 micrograms/dl) was
      detected with Sandell-Kolthoff colorimetric reaction. The most decreased urine
      iodine concentration was detected in the subgroups with arrhythmia and congestive
      heart failure (4.7 +/- 4.94 micrograms/dl and 4.9 +/- 4.81 micrograms/dl,
      respectively). An elevated TSH level was found by 3 patients (5.3 +/- 1.4 mlU/l).
      An elevation in lipid metabolism (cholesterol, triglyceride) associated with all
      subgroups without arrhythmia. In conclusion, the occurrence of iodine deficiency
      in cardiovascular disease is frequent. Iodine supplementation might prevent the
      worsing effect of iodine deficiency on cardiovascular disease.

PMID- 9755627
TI  - [Polysomnography in the prevention of crib death].
AB  - The authors stress the importance of polysomnography--a new electrophysiologic
      method--in the prevention of SIDS (cot death). SIDS is the most important and
      frequent cause of infant mortality between 1 and 12 months of age in western
      countries (nowadays between 1-2/1000!). In Hungary the frequency is not so high.
      In the last few years the incidence declined after the "back to sleep" campaigns,
      but to reach further success, it is very important to seek the so called "risk"
      babies. The unique cause of cot death is not yet understood exactly, but some
      instability in respiration (mostly during the sleep) is one of the accepted
      principal basic factors. The mentioned new method helps in choosing the SIDS risk
      infants from the "normal" population, allows to examine their respiratory
      irregularity or even disorders during the sleep and gives possibility for the
      prevention of lethal apneas. The authors describe the details of the prevention
      in case of abnormal polysomnography in their other publications.

PMID- 9755628
TI  - [Pacemaker syndrome without a pacemaker].
AB  - Circulatory consequences of cardiac arrhythmias are not always evident. Proper
      interpretation of the clinical symptoms in certain cases requires assessment of
      the patients' other hemodynamic characteristics. The authors present the case of
      a patient with left ventricular hypertrophy, who developed severe circulatory
      failure at the time of artrioventricular dyssynchrony in association with
      junctional rhythm. Analogy between the circulatory consequences of the junctional
      rhythm and ventricular pacing was documented by hemodynamic measurements. The
      patient was subsequently treated by implanting an atrioventricular pacemaker.

PMID- 9755629
TI  - [Quo vadis "suprema lex"?].

PMID- 9755630
TI  - [Computed tomographic angiography of the thoracic vessels: the method, initial
      experience and outlook for its use].
AB  - The paper presents the data available in the literature on computed tomographic
      angiography and the first experience with it to study thoracic vessels. It
      details the principles of spiral computed tomography and CT angiography.
      Practical aspects of their implementation, as well as basic concepts are
      outlined. It is concluded that CT angiography is promising in studying thoracic
      vessels in various abnormalities.

PMID- 9755631
TI  - [A comparative analysis of the immediate and late results of coronary balloon
      angioplasty in bifurcation stenoses performed by the traditional method and by
      the "2-guide" method].
AB  - To evaluate the efficiency of balloon coronary angioplasty (BCA) for bifurcation
      stenoses, which had been made by the two-guide method, the results of the
      angioplasties were examined in 147 patients with coronary heart disease. BCA had
      been performed routinely in 54 patients and by the two-guide method in 32. Sixty
      one patients undergone angioplasty for nonbifurcation lesions served as a control
      group. In the group of routine BCA procedure, poor results with residual stenosis
      of the major vessel were seen in 13% of cases, the incidence of complication
      (dissection of unfavourable types, thrombosis of the major vessel) was 29.6%. In
      the two-guide BCA, these indices were 15.6 and 2%, respectively, the incidence of
      restenosis was 46.9% and that of branch lesions was 6.3%. The findings have led
      to the following conclusions that routine angioplasty of bifurcation stenoses
      yields poor early and late results of dilatation of lateral branches. The use of
      the two-guide method substantially reduces the risk of damage to a lateral
      branch, improves immediate dilatation of the major vessel, yet fails to affect
      the number of restenosis in the late period.

PMID- 9755632
TI  - [The X-ray diagnosis of congenital absence of the pericardium].
AB  - The X-ray signs of such a rare abnormality as the congenital absence of the
      pericardium are presented. The results of examinations and follow-up of 4
      patients with this abnormality are analyzed. The patients underwent X-ray,
      echocardiographic studies, cardiac catheterization and angiography. The diagnosis
      of the absence of pericardium was confirmed at surgery and in one case at
      autopsy.

PMID- 9755633
TI  - [The puncture and catheterization of the peripheral vessels using ultrasonic
      scanning].
AB  - Having many-year experience with angiographic interventions, the authors examined
      the potentialities of ultrasonic angioscanning to monitor the implementation of
      endovascular interventions (EVI). During the study, they developed an original
      procedure of different EVI with intraoperative ultrasonic monitoring, refined the
      ultrasonic semiotics of the procedure, achieved positive results in preventing
      possible complications. The authors made indications for the procedure and
      rational ways of its application more concrete. They provide evidence for that
      the proposed procedure greatly facilitates the performance of different
      intravascular procedures and reduces the time (or excludes) teleradioscopy, thus
      lowering the radiation burden on the staff and the patient.

PMID- 9755634
TI  - [Diagnostic catheterization and angiography in the examination of patients with
      ischemic heart disease].

PMID- 9755635
TI  - [Experience in using at a polyclinic the Siberia low-dose digital X-ray unit].

PMID- 9755636
TI  - [Sarcoidosis of the respiratory organs: the problems of etiology and
      pathogenesis, classification and X-ray diagnosis].

PMID- 9755637
TI  - [The University of X-ray Laboratory Assistants. Lesson 5. Image contrast].

PMID- 9755638
TI  - [Magnetic resonance tomography and angiography in the assessment of the status of
      the kidneys and renal arteries in patients with renovascular hypertension].

PMID- 9755639
TI  - Molecular mechanisms of programmed cell death.
AB  - Programmed cell death and apoptosis have now been recognised as biological
      phenomena which are of fundamental importance to the integrity of organisms. What
      may have evolved as an altruistic defence against pathogen invasion in simple
      organisms is now a major regulatory mechanism in the development and maintenance
      of multi-cellular organisms. The classically defined morphological
      characteristics of apoptosis are now accompanied by a plethora of information
      regarding common biochemical and genetic mediators of programmed cell death. It
      is apparent that life and death decisions are taken by individual cells based on
      their interpretation of physiological signals, or their own self-assessment of
      internal damage. The knowledge that cell death is a genetically regulated process
      has highlighted an inherent potential for manipulation and offered new avenues
      for research into several diseases, and also productivity improvements in the
      biotechnology industry. This relatively "new frontier" in cell science has
      undoubtedly widened our perspectives and may provide novel strategies to expedite
      both medical and biotechnological research.

PMID- 9755640
TI  - Measurement of apoptosis.
AB  - The cell dying by apoptosis undergoes a sequence of morphological, biochemical,
      and molecular changes which are characteristic, and often unique, to this mode of
      cell death. Specific features of apoptotic cells resulting from these changes,
      which serve as markers used to reveal the apoptotic mode of cell death and to
      quantify the extent of apoptosis in cultures or in tissue, are reviewed. Analysis
      of these features by flow or image cytometry is the most commonly used approach
      to detect, quantify, and study various aspects of apoptosis. Flow or laser
      scanning cytometry also offer all the advantages of rapid, accurate and
      multiparametric measurements to investigate the biological processes associated
      with cell death. Numerous methods have been developed to identify apoptotic and
      necrotic cells, which are widely used in various disciplines, particularly in
      oncology and immunology. The methods based on changes in cell morphology, plasma
      membrane molecular structure and transport function, function of cell organelles,
      DNA stability to denaturation and endonucleolytic DNA degradation are reviewed
      and their applicability in the research laboratory and in the clinical setting is
      discussed. The most common pitfalls and improper use of the methodology in
      analysis of cell death and in data interpretation are also discussed.

PMID- 9755641
TI  - The Bcl-2 gene family and apoptosis.
AB  - Apoptosis, or programmed cell death, is an essential process for normal embryonic
      development, maintaining homeostasis in adult tissues, and suppressing
      carcinogenesis. The bcl-2 protein, discovered in association with follicular
      lymphoma, plays a prominent role in controlling apoptosis and enhancing cell
      survival in response to diverse apoptotic stimuli. The evolutionarily conserved
      bcl-2 protein is now recognized as being a member of a family of related proteins
      which can be categorized as death agonists or death antagonists. Progress in
      defining the role of bcl-2 and its family members in regulating apoptosis is
      rapidly advancing. This review describes, in detail, current bcl-2 family members
      and the possible mechanisms of function which allow the bcl-2 family of proteins
      to either promote or suppress cell death.

PMID- 9755642
TI  - The role of caspases in apoptosis.
AB  - The process of apoptosis, or programmed cell death, is fundamental during normal
      development and homeostasis and aberrant apoptosis has been implicated in a
      number of human diseases. The cellular machinery involved in the execution of
      apoptosis includes a family of cysteine proteases termed caspases. Caspases
      exhibit the rare substrate preference of cleavage C-terminal to aspartate
      residues, a property shared only by the cytotoxic lymphocyte serine protease,
      granzyme B. Experimental evidence demonstrates a vital role for caspase
      activation in the apoptotic pathway, and, as such, caspases are a target for the
      development of agents that can modulate their activity. This article reviews the
      members of the caspase family and the role that each contributes to the execution
      of cell death induced by apoptotic stimuli.

PMID- 9755643
TI  - "Tissue" transglutaminase and apoptosis.
AB  - In this paper we discuss the role of "tissue" transglutaminase (tTG) in
      apoptosis. This enzyme by catalizing the Ca(2+)-dependent cross-linking of
      intracellular proteins leads to the formation of the SDS-insoluble protein
      scaffold in cells undergoing programmed cell death. These intracellular
      structures confer resistance to mechanical and chemical attack to the
      polipeptides involved in the linkages. tTG is induced during apoptosis, in fact,
      tTG mRNA is transcripted as a consequence of apoptosis induction. Overexpression
      of tTG in many cell lines enhances their susceptibility to apoptosis, indicating
      a pivotal role for tTG in this process. In keeping with these findings
      transfection of the human tTG complementary DNA in antisense orientation leads in
      a pronounced decrease of both spontaneous as well as induced apoptosis.
      Interestingly, the identification of the tTG substrate proteins in cells
      undergoing apoptosis has evidenced that many of the tTG proteins are also
      substrates of caspases.

PMID- 9755644
TI  - Survival factors and apoptosis.
AB  - This chapter will explore the role of survival factors in suppression of
      apoptosis, and illustrate how survival signals play a critical role in the
      survival of both normal and tumor cells. Survival factors necessary for the
      development and maintenance of the nervous system and hemopoietic system will be
      surveyed. This will be followed by a detailed discussion of the role of insulin
      like growth factor I (IGF-I) and its receptor in suppression of apoptosis. The
      importance of survival signals from the IGF-IR for development and tumorigenesis
      will be discussed, and results of a mutational analysis of the receptor to assign
      domains necessary for suppression of apoptosis will be summarized. Finally, a
      discussion of the signal transduction pathways involved in survival factor
      signaling will review the roles played by PI-3 kinase and AKT and speculate on
      how activation of these kinases by survival factors might regulate the apoptotic
      pathway.

PMID- 9755645
TI  - Apoptosis and bioprocess technology.
AB  - Optimisation of the production of biopharmaceuticals in animal cell lines has
      become a key area of research. The identification of apoptosis as the major
      mechanism of cell death during such processes has raised the importance of
      studies of cell death when implementing culture optimisation strategies. In this
      article we present an overview of the studies which have demonstrated the
      induction of apoptosis during the cultivation of industrially important animal
      cell lines. We also discuss studies which have shown that deprivation of factors
      such as amino acids, glucose, serum and oxygen are potent inducers of apoptosis
      in industrial cultures. The suppression of apoptosis under these conditions has
      been demonstrated by a number of recent reports, and we describe ways in which
      this knowledge may be applied in the development of novel solutions to some of
      the technical problems associated with the development of successful large scale
      culture process. The article concludes with a discussion of future directions for
      apoptosis research in bioprocess technology.

PMID- 9755646
TI  - The outcome of parent training using the behavior management flow chart with
      mothers and their children with oppositional defiant disorder and attention
      deficit hyperactivity disorder.
AB  - The effects of parent training, using parameters established in the Behavior
      Management Flow Chart, on mother behavior and on the disruptive behavior of eight
      children who emitted behavior consistent with the diagnoses of both Oppositional
      Defiant Disorder and Attention-Deficit Hyperactivity Disorder were evaluated.
      There are important differences between the Behavior Management Flow Chart and
      well-known parent-training programs that are based on the Hanf model. Parent
      training was conducted within a multiple baseline design across children. Direct
      observation of mother and child behavior, phone interviews, and standardized
      rating scales showed that training improved parenting behavior, reduced maternal
      stress, and reduced oppositional child behavior. A 6-month follow-up revealed
      that parenting and child behavior remained stable. The results are comparable
      with prior research on behavioral parent training for families that have children
      with oppositional/hyperactive behavior.

PMID- 9755647
TI  - The effects of noncontingent and contingent attention for self-injury, manding,
      and collateral responses.
AB  - To date, most functional analysis studies have focused on the effects of
      treatment contingencies on specific targeted aberrant and alternative responses.
      In the current investigation, the main and collateral effects of the assessment
      and treatment of attention-maintained self-injury were assessed. Specifically, we
      evaluated the effects of noncontingent and contingent social attention on four
      categories of behavior: self-injury, a novel mand, preexisting prosocial
      responses (e.g., babbling and reaching out), and other aberrant responses (i.e.,
      aggression and destruction). Results suggested that self-injury, prosocial
      responses, and other aberrant behaviors were within the same functional response
      class. Possible impact of these results when selecting mands for functional
      communication training is discussed.

PMID- 9755648
TI  - Evaluating outpatient behavior therapy of sex offenders. A pretest-posttest
      study.
AB  - This study compared the entrance and exit scores of 16 patients completing
      treatment at the Highland Institute for Behavioral Change (HIBC), an outpatient
      program specializing in the behavioral treatment of sex offenders. Outcome
      measures included the Minnesota Multiphasic Personality Inventory (MMPI), the
      Multiphasic Sexual Inventory, and recidivism (rearrest record) posttreatment.
      Statistically significant and clinical improvements were obtained on a number of
      these measures. One of the 16 graduates reoffended during the average follow-up
      period of 26 months (he is now incarcerated). These data are supportive of the
      contention that outpatient behavior therapy can be effective in reducing deviant
      sexual arousal and in enhancing appropriate consensual sexual behavior.

PMID- 9755649
TI  - A supported relationships intervention to increase the social integration of
      persons with traumatic brain injuries.
AB  - A supported relationships intervention was used to increase the integrated social
      contacts (ISCs) of 3 persons with traumatic brain injury (TBI) who were each
      matched with 4 community participants. The intervention consisted of asking
      participants to meet with their matched counterpart to engage in leisure
      activities once per week for 4 weeks. Additionally, community participants were
      provided with a brief training session on TBI, were given specific suggestions on
      interacting with the persons with TBI with whom they were matched, and received
      weekly phone calls from the researcher. Frequency of ISCs were analyzed with a
      multiple baseline design across participants. All 3 participants with TBI
      increased the frequency of ISCs after implementation of the supported
      relationships intervention and continued to experience more than baseline levels
      of ISCs during 8 weeks of follow-up. These data suggest that social integration
      can be enhanced with a procedure requiring limited staff intervention.

PMID- 9755650
TI  - Use of noncontingent reinforcement in the treatment of challenging behavior. A
      review and clinical guide.
AB  - Recently, noncontingent reinforcement (NCR) has been used to reduce challenging
      behavior in persons with developmental disabilities. In this context, NCR
      involves reinforcement on a fixed-time schedule irrespective of behavior. The
      present article reviews studies involving NCR for the treatment of challenging
      behavior. Based on this review, a clinical guide for the implementation of NCR is
      delineated. NCR appears to depend on ensuring that reinforcement matches the
      function of the challenging behavior. Initially, noncontingent reinforcement
      should be provided on a continuous basis. The schedule can then be faded from
      continuous reinforcement to a more appropriate level in a number of ways. NCR can
      also be combined with additional educationally oriented interventions to promote
      skill development. Given its ease of implementation and other potential
      advantages, NCR would appear particularly relevant for applied settings. The
      clinical guide may offer some assistance to practitioners.

PMID- 9755651
TI  - Staff attitudes that impede the implementation of behavioral treatment programs.
AB  - Staff who have negative attitudes about behavioral treatments are less likely to
      implement them. Previous research suggests that negative attitudes are associated
      with staff burnout and perceived collegial support. A path analysis is conducted
      in this study to determine the direction of these effects. Ninety staff members
      who work in treatment programs for severely mentally ill adults completed
      measures of attitudes about behavior therapy, experience with behavior therapy,
      burnout, and collegial support. Results of the path analysis yielded a model with
      good fit that confirmed our hypotheses; namely, burnout leads to negative
      attitudes and experience with behavior therapy yields positive attitudes.
      Insufficient collegial support leads to negative attitudes through burnout.
      Implications of these findings for improving the use of behavior treatments in
      real-world programs are discussed.

PMID- 9755652
TI  - Behavioral treatment of pulsatile tinnitus and headache following traumatic head
      injury. Objective polygraphic assessment of change.
AB  - Pulsatile tinnitus is a disorder that can be extremely disabling. Nonetheless, it
      has not been well-researched in the fields of psychology or behavioral therapy.
      This article describes the evaluation and behavioral treatment of a gentleman
      with pulsatile tinnitus. The evaluation included polygraphic assessment of
      vasomotor and electromyographic function both before and after treatment. The
      results show that the combination of lifestyle modifications and specific
      behavioral interventions were successful in modifying not only self-report
      indices of functioning, but also the underlying physiology related to the
      disorder. The potential role of the various treatment components and the value of
      including polygraphic assessment for informing treatment and evaluating outcome
      are discussed.

PMID- 9755653
TI  - Obsessive-compulsive disorder--Part I.

PMID- 9755655
TI  - Diagnosis by computer.

PMID- 9755654
TI  - The social usefulness of self-esteem: a skeptical view.

PMID- 9755656
TI  - Experimental procedures and the placebo response.

PMID- 9755657
TI  - Poorly controlled?

PMID- 9755658
TI  - Gender, culture, and psychiatric symptoms.

PMID- 9755659
TI  - Schizophrenic mother and child.

PMID- 9755660
TI  - What is anxiety sensitivity?

PMID- 9755661
TI  - Detection of high-risk human papillomavirus nucleic acid in archival cervical
      smears.
AB  - OBJECTIVE: To test the usefulness of a commercial DNA hybridization assay for the
      detection of high-risk (HR) human papillomavirus (HPV) types in archival cervical
      smears and to compare the sensitivity with that of polymerase chain reaction
      (PCR) using consensus primers. STUDY DESIGN: Stained material was scraped from
      archival slides and the pellet volume noted. DNA was extracted using
      silica/guanidinium isothiocyanate and the quality checked by amplification of the
      beta-globin gene. HR-HPV DNA was detected using a commercial hybrid capture assay
      (HCA) and the results compared with an in-house amplification system with
      consensus primers. RESULTS: Of 156 archival smears stored for 12-13 years, 20
      were positive by HCA using an HR probe cocktail. Ninety-eight were also tested by
      PCR, and 35 were positive. The percentage of HPV-positive samples increased with
      the increasing size of the pellet. HR-HCA detected more positives in samples with
      high grade squamous intraepithelial lesion (moderate/severe dyskaryosis).
      CONCLUSION: Both hybridization by HCA and amplification by PCR could be used to
      detect genital HPV in archival smears. The general primers PCR detected more
      positives than HR-HCA but included HPV 6/11. While variation in sample size and
      prolonged storage may reduce the quality of DNA, the use of archival material for
      longitudinal studies of HPV presence is potentially worthwhile.

PMID- 9755662
TI  - Radiation-induced acute immediate nuclear abnormalities in oral cancer cells:
      serial cytologic evaluation.
AB  - OBJECTIVE: To evaluate the dose-response relationship of nuclear abnormalities in
      tumor cells collected by serial scrape smears from oral cancer patients on
      fractionated radiotherapy. STUDY DESIGN: The study included 31 patients with
      squamous cell carcinoma of the oral cavity treated by radiotherapy (60 Gy in 25
      fractions; 2.4 Gy per fraction). Serial scrape smears were taken from each tumor
      before treatment and after delivery of various fractions, usually 2 (4.8 Gy), 5
      (12.0 Gy), 8 (19.2 Gy) or 12 (28.8 Gy). The smears were stained by Giemsa stain
      and evaluated by light microscopy, and the number of micronucleated, binucleated,
      nuclear budded and multinucleated cells were scored. Their relation to cumulative
      dose was analyzed by Kruskal-Wallis one-way analysis of variance. The results
      were expressed in terms of 1,000 mononucleated cells. RESULTS: Even before
      treatment, most of the tumors showed various abnormally nucleated cells, and,
      despite the high intertumoral variation (as indicated by the high variance), all
      of them showed statistically significant dose-related increases. The mean values
      before treatment and after irradiation with 28.8 Gy, respectively, were 2.8 and
      19.5 (P < .0001) for micronucleated cells, 1.5 and 8.5 (P < .000001) for nuclear
      budded cells, 8.2 and 35.5 (P < .0001) for binucleated cells, and 3.7 and 16.8 (P
      < .0001) for multinucleated cells. When the different types of nuclear
      abnormalities were combined and analyzed as "abnormally nucleated cells," the
      mean count before treatment and after 28.8 Gy were 7.9 and 44.9 (P < .00001),
      respectively. CONCLUSION: The study showed that radiation-induced
      micronucleation, multinucleation, binucleation and nuclear budding in oral cancer
      cells has statistically significant dose-related increases that become evident in
      the initial few days of radiotherapy and that they can be differentiated well by
      cytology. This dose-response relationship and the high intertumoral variations
      suggest that serial assay of these changes has potential use for radiosensitivity
      prediction.

PMID- 9755663
TI  - Peritoneal washing cytology of ovarian tumors of low malignant potential:
      correlation with surface ovarian involvement and peritoneal implants.
AB  - OBJECTIVE: To correlate the cytologic diagnoses of peritoneal washings (PWs) with
      histologic findings of ovarian tumors of low malignant potential (LMP). METHODS:
      PW cytology from 90 patients with histologically confirmed ovarian tumors of LMP
      were reviewed and correlated with histologic findings. RESULTS: In 90 LMP tumor
      patients who underwent PW, cytologic diagnoses were reported as positive in 30
      (33%) cases, atypical in 5 (6%) cases and negative in 55 (61%) cases. On review
      of the five atypical cases, three were reclassified as negative and two as
      positive. Peritoneal washings were positive in 20 (33%) of 60 patients with
      serous LMP tumors, 12 (44%) of 27 patients with mucinous LMP tumors and none of 3
      patients with mixed LMP tumors. The presence of positive cytology was highly
      indicative of surface ovarian involvement or peritoneal implants in completely
      staged or selectively biopsied patients (P < .0001). Of 60 (67%) patients who had
      a staging laparotomy, positive PWs were seen in 3 (75%) of 4 cases with surface
      involvement only, 13 (94%) of 14 cases with peritoneal implants only, 3 (100%) of
      3 cases with both peritoneal implants and ovarian surface involvement, and 9
      (23%) of 39 cases without evidence of surface involvement or peritoneal implants.
      PWs were positive in 4 (13%) of 30 cases without staging laparotomy. CONCLUSION:
      PW cytology is a sensitive indicator of peritoneal dissemination of ovarian
      tumors of LMP. In addition, PWs will detect a high percentage of patients with
      subclinical intraperitoneal extension of such tumors and should be used routinely
      in the staging of ovarian tumors of LMP.

PMID- 9755664
TI  - Electron microscopic examination of cytologic samples.
AB  - OBJECTIVE: To review the results of observations of cytologic samples performed
      in our laboratory by light microscopy (LM), scanning electron microscopy (SEM)
      and transmission electron microscopy (TEM) performed in succession (LM-SEM-TEM
      examination) using the same cytologic sample and to assess the diagnostic value
      of this method of successive examination. STUDY DESIGN: Using a previously
      reported method of LM-SEM-TEM sample preparation and observation, we analyzed 201
      cytologic specimens over a seven-year period (1986-1993) and investigated whether
      the histologic origin and malignancy can be estimated from SEM and TEM findings
      on the cells. RESULTS: Observations of many cytologic samples over a seven-year
      period (by LM, SEM and TEM) showed that several basic interpretations of cellular
      ultrastructure are possible. In cases where cell identification was difficult by
      LM, electron microscopic findings were sometimes useful for determining the
      biologic characteristics of cells and for estimating their tissue origin.
      Electron microscopic findings also provided important information for
      cytodiagnosis. CONCLUSION: SEM and/or TEM findings are useful for determining the
      morphologic (including biologic) characteristics of cells in cases where they
      cannot be determined by LM. With the accumulation of data on electron microscopic
      examination of cytologic samples, it is expected that in the future, electron
      microscopy will continue to provide new information that can be used to improve
      the accuracy of cytodiagnosis by LM.

PMID- 9755665
TI  - Cytologic features of hemangioblastoma: comparison with meningioma, anaplastic
      astrocytoma and renal cell carcinoma.
AB  - OBJECTIVE: To compare the features of intraoperative smears of hemangioblastomas
      with those of tumors with which it is most likely to be confused: meningiomas,
      anaplastic astrocytomas and renal cell carcinomas. STUDY DESIGN: Examples of
      hemangioblastomas with high-quality intraoperative smears were retrieved from the
      files of University Hospital, University of Southern California and Los Angeles
      County-University of Southern California. The characteristics of these smears
      were compared to those of meningiomas, anaplastic astrocytomas and renal cell
      carcinomas by two observes. RESULTS: Smears of hemangioblastomas were cellular
      but remarkably cohesive. Cytoplasmic borders were indistinct. The nuclei were
      hyperchromatic and mildly pleomorphic and had a relatively evenly dispersed
      chromatin pattern. Hemosiderin was invariably present. Smears of meningiomas,
      anaplastic astrocytomas and renal cell carcinomas were more discohesive than
      those of hemangioblastomas. Smears of hemangioblastomas lacked the cytoplasmic
      fibrillarity of those of astrocytic neoplasms and distinct cytoplasmic borders
      seen in smears of renal cell carcinoma. The nuclear features of the four
      neoplasms studied also differed. CONCLUSION: Smears of hemangioblastomas have
      characteristic features that differ reliably from those of meningiomas,
      anaplastic astrocytoma and renal cell carcinoma, neoplasms that commonly enter
      the differential with hemangioblastoma. Thus, a cytologic smear preparation made
      at the time of frozen section may be an invaluable aid in the intraoperative
      diagnosis of hemangioblastoma.

PMID- 9755667
TI  - Extramedullary hematopoietic effusions.
AB  - OBJECTIVE: To investigate the frequency and diagnostic implications of
      extramedullary hematopoietic effusions. STUDY DESIGN: Smears of the effusions
      diagnosed cytologically as myeloid metaplasia or extramedullary hematopoiesis and
      their clinical records were reviewed and compared with the histologic diagnoses.
      RESULTS: There were 7 pleural and 1 peritoneal effusion from 5 patients out of
      20,793 pericardial, peritoneal and pleural effusions studied during a period of
      21 years. CONCLUSION: When compensatory responses can be ruled out, the diagnosis
      of extramedullary hematopoietic effusion points toward replacement of the bone
      marrow by a metastatic process. The first primary to consider in males is lung
      carcinoma.

PMID- 9755666
TI  - Malignant pleural effusions after resection of pulmonary adenocarcinoma.
AB  - OBJECTIVE: To evaluate the clinicopathologic features of malignant pleural
      effusions secondary to pulmonary adenocarcinoma in patients who have undergone
      surgical resection of the primary tumor. STUDY DESIGN: Clinical, pathologic and
      cytologic material from 19 patients who developed malignant pleural effusions
      after resection of pulmonary adenocarcinoma was reviewed. RESULTS: Malignant
      effusions developed only in patients with either lymph node or pleural
      involvement by neoplasm. Time to development of the effusion after resection and
      overall survival correlated with histologic findings. Malignant effusions in
      patients who survived > 24 months were secondary to another primary tumor (either
      breast or a new pulmonary carcinoma). Malignant effusions developed significantly
      sooner after resection (mean 5.0 +/- 2.0 months, median 5) in patients with lymph
      nodal metastases than in those with pleural involvement by neoplasm (mean 11.2 +/
      2.5 months, median 12) (Student's t test P = .01, Mann-Whitney U test .04).
      Nevertheless, survival after resection for patients with lymph node involvement
      (mean 9.0 +/- 3.6 months, median 8) and those with pleural involvement (mean 12.3
      +/- 2.5 months, median 12) was not significantly different. CONCLUSION: Malignant
      effusions developing in patients more than two years following resection of a
      pulmonary adenocarcinoma are likely to be secondary to another primary neoplasm.
      Lymph node and pleural involvement at the time of resection are risk factors for
      the development of a malignant effusion. Patients with lymph node involvement
      develop malignant effusions sooner than those with pleural involvement, but the
      overall survival is not significantly different.

PMID- 9755668
TI  - Marginal vacuoles in thyroid aspirates.
AB  - OBJECTIVES: To report on two cases of metastatic follicular carcinoma with
      marginal vacuoles (MVs) and review smear results in 441 solitary nodular goiters
      (SNGs) for this cytologic feature. STUDY DESIGN: The first case was a 55-year-old
      male who presented with a huge mass in the left hip region; the second case was a
      50-year-old male with a thyroid nodule and a large mass on the scalp. The age of
      the 441 ultrasonographically diagnosed SNG cases ranged from 11 to 75 years. The
      May-Grunwald-Giemsa-stained fine needle aspiration (FNA) smears of these cases
      were reviewed by one of the authors (D.K.D.) for various cytomorphologic
      features, including MVs. RESULTS: FNA smears from the mass in the hip in the
      first case showed follicular cells with acinar formation and MVs, indicating
      metastatic follicular thyroid carcinoma (FTC). These features were of help in
      detecting the thyroid primary, which had previously gone undetected. Aspiration
      smears from the thyroid nodule and the mass on the scalp in the second case
      showed tumor cells of FTC with MVs and microfilariae. Review of 441 SNG cases
      revealed MVs in 42.6% of hyperplastic nodules; that rate was significantly higher
      (P < .001) than that of colloid goiter (5.2%) and neoplastic goiter (13.3%) but
      lower (P < .05) than that of thyrotoxic goiter (100%). MVs were limited to
      neoplasms with a follicular component; that included 15% of follicular neoplasms
      and 50% of follicular variant of papillary carcinoma (FVPC). The difference
      between FVPC and the rest of the neoplastic goiters (6%) was statistically
      significant (P = .002).

PMID- 9755669
TI  - Bar-shaped nuclear chromatin in conjunctival samples: with cytologic features and
      ultrastructural correlation.
AB  - OBJECTIVE: To study the cytomorphologic features of bar-shaped chromatin in
      conjunctival samples and assess whether there are morphologic similarities
      between nuclear grooves seen in thyroid papillary carcinoma and bar-shaped
      chromatin. STUDY DESIGN: A total of 10 conjunctival samples from five volunteers
      were studied cytologically. Of the 10 samples, 2 showed barshaped chromatin. This
      chromatin was studied using a light microscope, scanning electron microscope
      (SEM) and transmission electron microscope (TEM). RESULTS: On SEM, bar-shaped
      chromatin was observed as a fissure or shallow cracks. On TEM the barshaped
      chromatin existed both in the center of the nuclei and in the nuclear membrane
      and cytoplasm. It was surrounded by outer and inner membranes. CONCLUSION: It
      seems that bar-shaped chromatin is formed by the nuclear membrane and that these
      changes are essentially the same configuration as cytoplasmic invaginations
      commonly present in papillary carcinoma of the thyroid.

PMID- 9755670
TI  - Rescreen effect in conventional and PAPNET screening: observed in a study using
      material enriched with positive smears.
AB  - OBJECTIVE: To study the rescreen and PAPNET effects on enriched material derived
      from smears screened routinely using PAPNET and conventional microscopy. STUDY
      DESIGN: A series of 432 smears (containing 122 atypical squamous cells of
      undetermined significance [ASCUS] plus 44 at least dysplastic squamous
      intraepithelial lesion-positive [SIL+] ones), screened routinely with the
      conventional method, were rescreened using the PAPNET system. Another series of
      461 smears (containing 140 ASCUS + 52 SIL+ ones) screened routinely with PAPNET
      were rescreened conventionally. The rescreen effect, defined as the effect of
      differences between the rescreen and routine screening situation, was
      investigated by comparing the rescreen results in both series of smears with the
      routine results in both series. The effect of using either method of screening
      was studied by comparing the PAPNET results in both series with the results of
      conventional screening in both series. RESULTS: The rescreen effect was
      statistically significant both for a higher number of smears classified as
      negative (less than ASCUS) and a higher number of smears classified as high grade
      SIL or more. PAPNET-assisted screening resulted in a significantly higher number
      of smears classified as high grade SIL+, although for this latter finding there
      is an unexplained significant difference between conventional and PAPNET-screened
      cases in the changes made by the cytopathologist in the cytotechnologists'
      diagnoses. CONCLUSION: The rescreen effect should not be ignored when enriched
      material is used.

PMID- 9755671
TI  - The immediate postconization endocervical smear: evaluation of its utility in the
      detection of residual dysplasia.
AB  - OBJECTIVE: To determine the diagnostic value of obtaining an endocervical smear
      for cytologic examination immediately following cervical conization (by either
      the loop electrosurgical excision procedure or large loop excision of the
      transformation zone) in the detection of residual squamous dysplasia. STUDY
      DESIGN: Thirty-eight cases were identified in which cervical conization was
      immediately followed by endocervical sampling (most commonly using a brush) and
      smear. RESULTS: Twenty-one of the 38 postconization endocervical smears (55%)
      were either unsatisfactory or sub-optimal for evaluation due to cellular
      distortion (i.e., cautery artifact), degeneration or obscuring blood. Histologic
      in evaluation showed negative endocervical margins in 32 cases (84%) and positive
      endocervical margins in 6 cases (16%), including both low and high grade squamous
      intraepithelial lesions. The endocervical smears in the 32 cases with a negative
      surgical margin did not demonstrate evidence of dysplasia. However, in the six
      cases with histologically positive margins, postconization endocervical smears
      also failed to identify any evidence of dysplasia. CONCLUSION: Immediate
      postconization endocervical smears do not appear to be useful for the detection
      of residual disease in patients undergoing conization for squamous dysplasia of
      the cervix.

PMID- 9755672
TI  - Cell block preparation of a Burkitt's lymphoma cell line as a positive control
      for in situ hybridization for Epstein-Barr virus.
AB  - OBJECTIVE: To examine the feasibility of the use of a cell block preparation of
      Epstein-Barr virus (EBV)-infected Burkitt's lymphoma cell line (EB-3) as a
      positive control for in situ hybridization (ISH) for EBV-encoded RNA (EBER).
      STUDY DESIGN: EB-3 cells were processed into cell block and cytocentrifuge
      preparations. ISH for EBER was performed, and the results were compared with a
      commercially available EBV positive control slide (cytocentrifuge). RESULTS: The
      cost of preparing the cell block and cytocentrifuge sample was only a fraction of
      the price of commercial control slides. ISH for EBER was strongly stained in all
      preparations with similar intensity of staining but with a much higher number of
      positive cells in the cell block. Although the cellular details in the cell block
      were considerably inferior to those on the cytocentrifuge and commercial control
      slide, with distortion of nuclei and smudging of chromatin, the interpretation of
      the ISH results was unaffected. The cell block was stable at room temperature
      when examined after one year. CONCLUSION: The cell block preparation of an EBV
      infected Burkitt's lymphoma cell line serves as a reliable, stable and a
      relatively inexpensive control, with good preservation of cellular details of
      cellular RNA for ISH study for EBER in the detection of latent infection with
      EBV.

PMID- 9755673
TI  - Squash preparation and frozen section in intraoperative diagnosis of central
      nervous system tumors.
AB  - OBJECTIVE: To investigate the diagnostic accuracy of squash preparation (smears)
      and frozen section (FS) in the rapid intraoperative diagnosis of central nervous
      system (CNS) tumors. STUDY DESIGN: One hundred eighty-three CNS tumors were
      examined over a period of 18 months (January 1995-June 1996). All these were open
      biopsies, and the smear interpretation was compared with FS findings and paraffin
      section diagnosis. RESULTS: In 183 tumors, squash preparation was satisfactory in
      156 cases (85.2%), and the diagnostic accuracy was 89.7% (140/156). The accuracy
      of FS diagnosis was 90.4% (141/156). CONCLUSION: The squash smear preparation is
      a fairly accurate and reliable tool in the rapid intraoperative diagnosis of CNS
      tumors. The accuracy of this technique is nearly as good as that of FS (P value =
      .9877). With the advent of stereotactic biopsies, the pathologist may have to
      depend entirely upon cytologic features for a definitive diagnosis.

PMID- 9755674
TI  - Fine needle aspiration cytology of malignant chondroid syringoma: a case report.
AB  - BACKGROUND: Chondroid syringoma, a tumor of the eccrine glands, was previously
      called mixed tumor of skin as it has both mesenchymal and epithelial elements.
      Malignancy in this tumor is extremely rare. Although there are a few reports
      describing the cytomorphologic features of chondroid syringoma, the cytologic
      findings of its malignant counterpart have not been described. CASE: A 40-year
      old female presented with a recurrent swelling on the scalp of one year's
      duration. Fine needle aspiration yielded blood-mixed gelatinous material. May
      Grunwald-Giemsastained smears showed epithelial cells arranged in cordlike
      structures and ill-formed glands against a myxomatous background. The epithelial
      cells had scanty cytoplasm and markedly pleomorphic nuclei with prominent
      nucleoli. A few cells in the stroma had a halo around them and a resemblance to
      cartilage cells. A preoperative diagnosis of malignant chondroid syringoma was
      made. The tumor was excised, and the cytologic diagnosis was confirmed on
      histopathology. CONCLUSION: Cytomorphologic features of a rare case of malignant
      chondroid syringoma are reported for the first time. The presence of malignant
      epithelial cells against a myxoid background with a few chondroid foci helped in
      making a correct preoperative diagnosis.

PMID- 9755675
TI  - Fine needle aspiration cytology of gastric solitary fibrous tumor: a case report.
AB  - BACKGROUND: Solitary fibrous tumors (SFT) occur mainly in the pleura and other
      serosal sites. However, they have been found in extraserosal sites and should be
      considered in the differential diagnosis (DDx) of any spindle cell lesion,
      including those in the gastrointestinal tract. In this report, we describe fine
      needle aspiration (FNA) cytologic evaluation of a gastric SFT, emphasizing the
      role of immunocytochemistry in the DDx. CASE: Computerized tomography-guided FNA
      of a subserosal gastric mass in a 77-year-old female was performed. The
      moderately cellular smears showed neoplastic cells arranged in interlacing
      fascicles and in a "patternless" pattern. There was variable collagenous stroma.
      The cell block revealed a similar pattern, with a single mitotic figure. Nuclear
      atypia and necrosis were absent. The neoplastic cells were strongly reactive for
      vimentin and CD34, with weak focal reactivity for smooth muscle actin, suggestive
      of vessels in tangential section. They were nonreactive for muscle specific
      actin, desmin, S-100 and pancytokeratin. Other immunocytochemical markers were
      also studied. CONCLUSION: SFT should be considered in the DDx of spindle cell
      lesion of the stomach. Cell block and immunocytochemical markers, especially
      CD34, were extremely useful in the diagnosis of SFT on FNA.

PMID- 9755676
TI  - Aspiration cytology of ectopic cervical thymoma mimicking a thyroid mass. A case
      report.
AB  - BACKGROUND: Ectopic cervical thymoma, first described in 1941 by Boman, is an
      uncommon tumor of the neck displaying the same histologic features as mediastinal
      thymoma. Since it is commonly located in the anterolateral part of the neck or is
      subjacent to or inside the lower pole of the thyroid, the mass is often confused
      as being of thyroid origin. CASE: A 68-year-old female presented with dyspnea and
      an anterior neck mass found on routine chest roentgenography. The thyroid scan
      showed a cold nodule in the lower pole of the left part of the thyroid. Fine
      needle aspiration (FNA) cytology revealed large numbers of small lymphocytes with
      hyperchromatic nuclei and frequent clumping pattern in the pale, eosinophilic,
      fluid background. A few clusters of epithelial cells without atypism were
      interpreted as thyroid follicular cells. The overall cytologic features were
      misinterpreted as malignant lymphoma of the thyroid. However, the histologic
      diagnosis was thymoma, predominantly cortical type. CONCLUSION: The ectopic
      cervical thymoma is sometimes misdiagnosed as Hashimoto's thyroiditis, anaplastic
      carcinoma and malignant lymphoma of thyroid on FNA cytology or frozen diagnosis
      due to its rarity. Therefore, the differential diagnosis of a neck mass showing a
      variable composition of lymphocyte and epithelial component in a pale,
      eosinophilic, fluid background should also include ectopic cervical thymoma,
      especially in elderly females.

PMID- 9755677
TI  - Fine needle aspiration cytology of fibrous dysplasia: a case report.
AB  - BACKGROUND: Fibrous dysplasia (FD) is a benign disorder of bone consisting of
      intramedullary proliferation of fibrous tissue and irregularly distributed,
      poorly developed bone. Although tumorlike in appearance, FD is probably a
      condition resulting from failure of maturation from woven to lamellar bone. The
      histology of FD has been well characterized since Lichtenstein first reported it,
      in 1938; however, the cytologic appearance has been described only rarely. To our
      knowledge, this is the first case report of fine needle aspiration (FNA)
      cytomorphology of FD. CASE: A 30-year-old female with breast carcinoma, diagnosed
      a month earlier, underwent computed tomography-guided FNA of a rib lesion
      radiologically thought to represent FD, although metastatic cancer could not be
      excluded. The smears contained blood, occasional osteoclastic multinucleated
      giant cells and frequent C-shaped fibrillary structures with dark central areas
      and lighter peripheries, representing woven bone. The cytologic/radiologic
      impression of FD was confirmed histologically. CONCLUSION: FNA cytodiagnosis of
      FD is possible in the setting of consistent clinical and radiologic findings.

PMID- 9755678
TI  - Cytodiagnosis of malignant melanoma of soft tissue: report of a case with
      diagnosis by intraoperative cytology.
AB  - BACKGROUND: Malignant melanoma of soft tissue (MMST) is a rare tumor and consists
      of < 1% of all soft tissue neoplasms. There are few reports on its cytodiagnosis.
      CASE: A 14-year-old male attended the Department of Orthopedics, Juntendo
      University Urayasu Hospital, in August 1994 because of a painless tumor in the
      distal portion of the left thigh. Intraoperative imprint smear examination led to
      a diagnosis of malignant melanoma, and wide resection of the tumor, including the
      surrounding normal tissue, was performed. On cytologic examination, the
      background was relatively clean, with tumor cells distributing individually or in
      clusters. Under high magnification, the tumor cells were seen to contain a
      slightly enlarged, conspicuous nucleolus and large cell body. The cells varied in
      shape from polygonal to spindle shaped, with a few multinuclear giant cells.
      Melanin and glycogen were observed in varying degrees in the tumor cells.
      CONCLUSION: MMST can be diagnosed easily if melanin is observed in the cytoplasm.
      Even in the absence of melanin, the tumor has relatively characteristic
      cytomorphology. Intraoperative cytology is useful for an accurate diagnosis of
      the tumor.

PMID- 9755679
TI  - Sclerosing lipogranuloma of the scrotum: report of a case with fine needle
      aspiration biopsy findings.
AB  - BACKGROUND: Sclerosing lipogranuloma of the scrotum is a rare granulomatous
      lesion of the subcutis. To the best of our knowledge, there have been no English
      language reports dealing with its cytologic findings. CASE: A fine needle
      aspiration specimen from a mass in the scrotum in a 62-year-old male showed
      epithelioid cells, multinucleated giant cells and fibroblasts, which were
      suggestive of sclerosing lipogranuloma. The diagnosis was confirmed by histology
      of the resected specimen. CONCLUSION: Fine needle aspiration cytology is useful
      for the diagnosis of sclerosing lipogranuloma. It is important, however, to
      interpret the fine needle aspiration cytology specimen in conjunction with the
      clinical information.

PMID- 9755680
TI  - Macrofollicular variant of papillary thyroid carcinoma diagnosed by fine needle
      aspiration biopsy: a case report.
AB  - BACKGROUND: Macrofollicular variant of papillary thyroid carcinoma (PTC) is an
      uncommon, recently described thyroid tumor. By frozen section it can be confused
      easily with goiter or macrofollicular adenoma. CASE: A 41-year-old female
      presented with a huge mass in the right thyroid lobe, cold on scintigraphy. By
      fine needle aspiration fluid was obtained. Smears of the sediment of the fluid
      showed epithelial cells with morphologic features diagnostic of PTC. Frozen
      section diagnosis was benign. CONCLUSION: This is the first reported case of
      macrofollicular variant of PTC diagnosed preoperatively by cytology. In our case
      the cytology was similar to that of cystic PTC.

PMID- 9755681
TI  - Gastrointestinal autonomic nerve tumor (plexosarcoma): report of a case with fine
      needle aspiration biopsy and histologic, immunocytochemical and ultrastructural
      study.
AB  - BACKGROUND: Gastrointestinal stromal tumors (GISTs) encompass a large group of
      mesenchymal neoplasms that display common cytologic spindle-shaped morphology on
      light microscopy. Immunocytochemical and ultrastructural studies can demonstrate
      several patterns of differentiation. CASE: A 70-year-old male presented with two
      intraabdominal small bowel masses. The cytopathologic features of a fine needle
      aspiration biopsy (FNAB) included plump spindle cells in densely populated
      aggregates or in a fasciculated pattern, without significant pleomorphism. An
      epithelioid component in a lobular arrangement with abundant, eosinophilic
      cytoplasm was also noted. The nuclei were vesicular, with a very evident,
      eosinophilic nucleolus and finely distributed chromatin. Groups of loosely
      cohesive cells with slender, dendritic-like cytoplasm were evident.
      Immunocytochemical study of the embedded, fine needle aspirated fragments of the
      neoplasm demonstrated immunoreactivity for vimentin and neuron-specific enolase.
      Cytokeratin immunoreactivity or muscular, vascular, neuroendocrine or nerve
      sheath differentiation failed to be demonstrated. The cytologic and
      immunocytochemical findings correlated well with the histologic features of the
      neoplasm. The morphologic diagnosis was confirmed by ultrastructural study.
      CONCLUSION: FNAB and immunocytochemistry can be valuable in making the correct
      diagnosis between gastrointestinal stromal tumors.

PMID- 9755682
TI  - Recurrent secondary hyperparathyroidism after autotransplantation into the
      sternocleidomastoid muscle: report of a case with fine needle aspiration
      findings.
AB  - BACKGROUND: Recurrent hyperparathyroidism may occur following parathyroid
      autotransplantation due to autogenous function of the muscle-engrafted tissue.
      Parathyroid lesions are uncommonly diagnosed on cytology. CASE: A 31-year-old
      female with chronic renal failure presented with an elevated parathyroid hormone
      level and a neck mass in the left sternocleidomastoid muscle, the site of a
      previous parathyroid autograft. Fine needle aspiration of the mass revealed high
      cellularity, with perivascularly arranged, three-dimensional, branching clusters;
      individual cells; and naked nuclei exhibiting anisonucleosis. A diagnosis of
      parathyroid graft hyperplasia was made by fine needle aspiration and subsequently
      by histopathologic examination. CONCLUSION: Fine needle aspiration is an
      effective tool for confirming the presence of parathyroid autograft hyperplasia,
      thus allowing the correct surgical approach.

PMID- 9755683
TI  - Primary small cell anaplastic carcinoma of the breast diagnosed by fine needle
      aspiration cytology: a case report.
AB  - BACKGROUND: Small cell anaplastic carcinoma most commonly presents as a lesion in
      the central portion of the lung but occasionally is found in peripheral
      locations. Only seven cases originating in the breast have been described. To our
      knowledge, the preoperative diagnosis of this entity by fine needle aspiration
      has not been previously reported in the cytologic literature. CASE: A 67-year-old
      female presented with a 4 x 3-cm, rapidly growing mass in the left breast. On
      fine needle aspiration (FNA) the tumor was soft to the needle and yielded a
      highly cellular aspirate. CONCLUSION: In this case the morphologic interpretation
      of FNA, combined with the immunocytochemical demonstration of neuron-specific
      enolase in tumor cells, was extremely helpful in establishing the nature of the
      breast tumor.

PMID- 9755684
TI  - AgNOR evaluation in pulmonary aspiration cytology.

PMID- 9755685
TI  - Current state of malpractice litigation.

PMID- 9755686
TI  - Breast metastases.

PMID- 9755687
TI  - Plant cells mimicking adenocarcinoma in sputum.

PMID- 9755689
TI  - Echinococcus oligarthrus.

PMID- 9755688
TI  - Infarction of a thyroid nodule after fine needle aspiration biopsy.

PMID- 9755690
TI  - Necrosis and Charcot-Leyden crystals.

PMID- 9755691
TI  - A proposed methodology for evaluating secondary screening (rescreening)
      instruments for gynecologic cytology: Intersociety Working Group for Cytology
      Technologies.

PMID- 9755692
TI  - Diffusion-weighted MR imaging of acute cerebral ischemia.
AB  - Diffusion-weighted MR imaging has been used in studies on experimental animal
      models and on patients with acute cerebral ischemia. Compared with CT and
      conventional MR techniques, diffusion-weighted imaging can provide earlier and
      more precise detection of the location and the extent of an ischemic lesion
      during the critical first few hours after the onset of stroke. Quantitative
      apparent diffusion coefficient (ADC) mapping of the brain water can also be
      carried out by recording a series of diffusion-weighted images with different
      amplitudes of the displacement encoding gradients. ADC maps can provide important
      information about the extra- and intracellular water homeostasis. ADC reduction
      of the tissue water is one of the early signals of the pathophysiological cascade
      resulting from ischemic tissue injury. Diffusion MR imaging has become a valuable
      tool in stroke research. It may also prove a valuable tool in monitoring the
      efficiency of therapeutic effects in stroke patients. It is our intention to
      provide an overview of the recent development in this area with emphasis on the
      diffusion-weighted MR techniques, and to discuss the possible underlying
      biophysical mechanisms responsible for the contrast of diffusion-weighted
      imaging.

PMID- 9755693
TI  - The effect of paramagnetic contrast media on T1 relaxation times in brain tumors.
AB  - PURPOSE: To study T1 relaxation times in brain tumors before and after
      paramagnetic contrast medium injection. MATERIAL AND METHODS: Seventeen patients
      with a known or suspected brain tumor were studied with an echo planar inversion
      recovery imaging sequence using 10 different inversion times. Double injections
      of Gd chelate (0.1 mmol/kg + 0.2 mmol/kg) were administered in 5 patients, and a
      single 0.2-mmol/kg dose in 12 patients. RESULTS: After the 0.2-mmol/kg dose, T1
      decreased from 1121 +/- 130 ms to 987 +/- 103 ms in gray matter (p < 0.001), and
      from 666 +/- 29 ms to 646 +/- 27 ms in white matter (p < 0.001). Tumor T1
      shortened from 1515 +/- 319 ms to 717 +/- 383 ms. After the 0.1-mmol/kg dose (n =
      5), tumor T1 decreased from 1116 +/- 261 ms to 793 +/- 202 ms and after the
      additional 0.2-mmol/kg dose it decreased further to 526 +/- 141 ms. CONCLUSION:
      Postcontrast T1 relaxation times in tumors showed considerable variation and
      remained, on average, relatively long compared to white matter. This should be
      taken into account when deciding which pulse sequences, imaging parameters, and
      contrast agent doses are optimal for brain tumor imaging.

PMID- 9755694
TI  - White matter abnormalities in tuberous sclerosis complex.
AB  - PURPOSE: The aim of this study was to investigate and describe the range of white
      matter abnormalities in children with tuberous sclerosis complex by means of MR
      imaging. MATERIAL AND METHODS: A retrospective cross-sectional study was
      performed on the basis of MR imaging findings in 20 cases of tuberous sclerosis
      complex in children aged 17 years or younger. RESULTS: White matter abnormalities
      were present in 19/20 (95%) cases of tuberous sclerosis complex. These were most
      frequently (19/20 cases) found in relation to cortical tubers in the
      supratentorial compartment. White matter abnormalities related to tubers were
      found in the cerebellum in 3/20 (15%) cases. White matter abnormalities described
      as radial migration lines were found in relation to 5 tubers in 3 (15%) children.
      In 4/20 (20%) cases, white matter abnormalities were found that were not related
      to cortical tubers. These areas had the appearance of white matter cysts in 3
      cases and infarction in the fourth. In the latter case there was a definable
      event in the clinical history, supporting the diagnosis of stroke. CONCLUSION: A
      range of white matter abnormalities were found by MR imaging in tuberous
      sclerosis complex, the commonest being gliosis and hypomyelination related to
      cortical tubers. Radial migration lines were seen infrequently in relation to
      cortical tubers and these are thought to represent heterotopic glia and neurons
      along the expected path of cortical migration.

PMID- 9755695
TI  - An experimental high-resolution MR coil for the imaging of pathological findings
      in the post mortem brain stem.
AB  - PURPOSE: The purpose of this study was to evaluate the potential of an
      experimental coil using a whole-body MR unit to delineate pathological changes
      within formalin-fixed human brain stems. MATERIAL, METHODS, AND RESULTS: The MR
      images of 9 brain stems were compared with gross anatomy and corresponding
      histological sections. The resolution of the images was high enough to depict
      areas of clinically relevant pathological alterations.

PMID- 9755696
TI  - MR findings in three pituitary abscesses. Case reports.
AB  - We present MR findings in 3 surgically proved cases of pituitary abscess. All
      lesions were seen as a sellar cystic mass with a thin rim of enhancement. In
      addition, the pituitary stalk was thickened in 2 cases in which central diabetes
      insipidus developed. These findings may be suggestive of pituitary abscess.

PMID- 9755697
TI  - Mechanism of contrast enhancement in breast lesions at MR imaging.
AB  - PURPOSE: The aim of the study was to explain why breast lesions are enhanced by
      contrast medium at MR imaging and to elucidate the histopathological basis for
      the overlap in the enhancement patterns of benign and malignant breast lesions.
      MATERIAL AND METHODS: Ten invasive breast carcinomas and 10 benign breast lesions
      were selected for the study. Of the 10 carcinomas, 5 showed a strong and early
      contrast enhancement, and 5 did not. Of the 10 benign lesions, 5 showed a strong
      and early contrast enhancement, and 5 showed no enhancement. The following
      morphometric variables were evaluated: proliferation cell index of neoplastic
      parenchymal cells, S-phase fraction, nuclear ploidy analysed by image DNA
      cytometry, microvessel density, and the percentage proportion of the interstitial
      area. RESULTS: Contrast enhancement was related to the proliferating activity of
      the hyperplastic or neoplastic parenchymal cells and was inversely correlated
      with the interstitial area in carcinomas as well as in benign tumours and non
      neoplastic lesions of the breast. CONCLUSION: Morphometric variables play an
      important role in the general mechanism of MR contrast enhancement in
      examinations of the breast and explain the histopathological basis for the
      overlap in the enhancement patterns of benign and malignant breast lesions.

PMID- 9755698
TI  - Detectability of simulated masses and calcifications in mammography. Development
      of a phantom and a new method for determination of receiver operating
      characteristics.
AB  - PURPOSE: To develop a method for receiver operating characteristics (ROC) studies
      in mammography. MATERIAL AND METHODS: We developed a phantom based on excised
      breast tissue and overlay tiles that could be arranged in an arbitrary pattern
      across the surface of the breast tissue. Some of the tiles contained structures
      simulating calcifications or masses that produced image contrast near the
      experimentally determined detection threshold. Based on this phantom, a
      methodology for performing ROC studies in mammography was developed. The ROC
      curves were constructed from reporting schemes filled in by radiologists at five
      different laboratories. The curves were determined by a novel method: a non
      linear least-squares fit of a mathematical model to the data. RESULTS: There were
      large differences among the areas under the ROC curves obtained from the five
      laboratories.

PMID- 9755699
TI  - Assessment of image quality and total performance in Norwegian mammography
      laboratories. Findings in a national survey based on different phantoms and ROC
      methodology.
AB  - PURPOSE: To assess the image quality at different mammography laboratories.
      MATERIAL AND METHODS: Two commercial mammographic test phantoms and one phantom
      based on excised mammary tissue were used in an assessment of the imaging chain
      and total performance at 45 Norwegian mammography laboratories. The breast-tissue
      phantom was used for a receiver operating characteristics (ROC) analysis. This
      was carried out by putting overlays with identifiable regions (some of which
      contained a cluster of simulated calcifications) on top of the mammary tissue,
      and then having a radiologist report the confidence of a finding for each region.
      RESULTS AND CONCLUSION: The areas under the ROC curves were in general high. In
      nearly all the laboratories, performance was improved when a magnification
      technique was applied. There were wide variations among the laboratories in total
      performance as measured by the area under the ROC curve, and also in the physical
      parameters derived by means of the commercial phantoms. In general, a good ROC
      performance was associated with a good physical performance in the imaging chain.

PMID- 9755700
TI  - Dose reduction in thorax radiography in simulated neonates with additional
      filtration and digital luminescence radiography.
AB  - PURPOSE: To determine the minimum acceptable radiation dose for an adequate image
      quality in thorax a.p. radiographs of neonates using mobile X-ray equipment.
      MATERIAL AND METHODS: The influence of additional filtration (1.0 mm Al + 0.1 mm
      Cu) on image quality and radiation dose was determined for the speed class 400
      screen-film system (SFS) and digital luminescence radiography (DLR) by making
      radiographs of a test phantom. Conventional and digital thorax a.p. radiographs
      of a rabbit were produced using various tube current-time products. The quality
      of the rabbit radiographs was judged by eight radiologists applying image quality
      criteria according to the German guidelines and the recommendations of the
      European Community. RESULTS: The added filter resulted in a dose reduction of 39%
      at 66 kV. DLR gave a further dose reduction of 25% in comparison to the speed
      class 400 SFS while maintaining adequate image quality, i.e. the radiographs were
      clinically acceptable with regard to quality criteria. CONCLUSION: The radiation
      dose resulting from thorax a.p. radiographs of neonates can be reduced by
      approximately 50% with the use of additional filtration and DLR.

PMID- 9755701
TI  - Pleural pneumatocoeles mimicking congenital cystic adenomatoid malformation of
      the lung. A case report.
AB  - We present the plain radiographic and CT appearances of large intrapleural
      pneumatocoeles in a 13-week-old infant, resulting in compression atelectasis of
      the left upper and lower lobes, and mimicking congenital cystic adenomatoid
      malformation.

PMID- 9755702
TI  - Clinical value of imaging techniques in childhood osteomyelitis.
AB  - PURPOSE: The traditional approach to investigating suspected osteomyelitis in
      children includes conventional radiography and bone scintigraphy. The roles of
      US, CT and MR imaging are controversial. Our objective was to determine whether
      the additional use of these modalities would yield information likely to lead to
      treatment modification. MATERIAL AND METHODS: Sixty-five children with clinically
      suspected osteomyelitis took part in a prospective study. All patients underwent
      conventional radiography and bone scintigraphy. In addition to this, US, CT and
      MR imaging were all performed in 33 patients; the remaining 32 patients were
      examined with various combinations of these three modalities. The value of the
      additional information obtained was estimated retrospectively by a pediatric
      orthopedic surgeon in terms of possible modification of treatment. RESULTS: MR
      imaging was the modality with the highest sensitivity and specificity for
      detecting osteomyelitis. MR yielded information likely to influence treatment in
      the greatest proportion of patients (45%) followed by US (30%). CONCLUSION: The
      standard investigation protocol with the addition of US (because of its ability
      to detect subperiosteal abscesses early and simply) is adequate in uncomplicated
      cases. When additional imaging is required to outline a lesion, or in complicated
      cases, and when bone scintigraphy is inconclusive, MR imaging should also be
      performed. CT should be considered when MR investigation is not available or when
      anesthesia is required but cannot be provided.

PMID- 9755703
TI  - Synovitis in Legg-Calve-Perthes disease. Evaluation with MR imaging in 84 hips.
AB  - PURPOSE: To evaluate, by means of MR imaging, the degree and persistence of
      synovitis in the hip joint in Legg-Calve-Perthes disease and to correlate the
      degree of synovitis with the degree of epiphyseal necrosis. MATERIAL AND METHODS:
      A total of 170 MR images in 72 patients (84 hips) were examined. The T2-weighted
      MR images were taken in the coronal plane in order to evaluate the degree of
      synovitis in the hip joint. RESULTS: MR revealed synovitis in all cases in the
      early phase of the disease. In Catterall group II, synovitis was discreet to
      moderate for up to 6 months after diagnosis. Hips with more severe necrosis,
      Catterall groups III and IV, had moderate or intense degrees of synovitis. There
      was a correlation between the degree of synovitis and the lateral pillar
      classification according to HERRING et al. Also, there was a good correlation
      between the extent of signal changes in the epiphysis on MR imaging and the
      degree of synovitis. There was no difference when signal changes were evaluated
      on T1- or T2-weighted images. Signs of synovitis could be seen for up to 30
      months after diagnosis in Catterall group I hips, and in Catterall groups II and
      III for up to 36 months, and in 2 cases even longer. Some Catterall group IV hips
      had discreet or mild synovitis for 60 months or more, after diagnosis.
      CONCLUSION: The degree of synovitis on MR imaging correlates to the extent of
      epiphyseal necrosis seen on radiographs or MR imaging as well as to the lateral
      pillar classification, i.e. to a poor clinical outcome. In Catterall group IV
      hips, synovitis can even persist for up to 60 months after diagnosis.

PMID- 9755704
TI  - Bone mineral density and spongiosa architecture in correlation to vertebral body
      insufficiency fractures.
AB  - OBJECTIVE: The clinical value of spinal quantitative CT (sQCT) and the structural
      patterns of the vertebral bone were studied. MATERIAL AND METHODS: sQCT was
      performed on 246 patients with a mean age of 57 years for whom conventional
      lateral radiographies of the thoracic and lumbar spine were available. All
      patients were suffering from back pain of unknown etiology. The bone mineral
      density (BMD) of the midvertebral section of 3 lumbar vertebral bodies was
      determined by means of single-energy-(SE)-weighted QCT (85 kV). Spongiosa
      architecture and density profile analyses were made in the axial images. This was
      contrasted to BMD values ascertained in SE QCT. The mean BMD was compared to the
      number of fractures and the patients were divided into three groups: group I--no
      fracture; group II--one fracture; and group III > 1 fracture. RESULTS: The mean
      BMD was: 134.3 (74.1-187.5) mg hydroxyapatite (HA)/ml in group I; 79.6 (58.6
      114.3) mg HA/ml in group II; and 52.4 (13.1-79.1) mg HA/ml in group III. A
      significant deterioration in spongiosa structure was found with increasing
      demineralization: strongly rarefied patterns predominated in the fracture groups
      II and III. CONCLUSION: sQCT provides a good risk assessment of the occurrence of
      vertebral body insufficiency fractures.

PMID- 9755705
TI  - Functional MR imaging of the cervical spine in patients with rheumatoid
      arthritis.
AB  - PURPOSE: To evaluate functional MR imaging in patients with rheumatoid arthritis
      (RA) involving the cervical spine. MATERIAL AND METHODS: We used a device that
      allows MR examination to be made of the cervical spine in infinitely variable
      degrees of flexion and extension. Dynamic functional MR imaging was performed on
      25 patients with RA. RESULTS: Functional MR imaging was able to show the degree
      of vertebral instability of the occipito-atlantal or atlanto-axial level as well
      as the subaxial level. By performing functional MR imaging, we were able to
      demonstrate the extent of synovial tissue around the dens, and the impingement
      and displacement of the spinal cord during flexion and extension. The basilar
      impression, the cord impingement into the foramen magnum, the cord compression,
      the slipping of vertebrae, and the angulation of the cord were all much more
      evident in functional than in static MR imaging. CONCLUSION: Functional MR
      imaging provided additional information in patients with RA, and is valuable in
      patients who have a normal MR study in the neutral position and yet have signs of
      a neurological deficit. Functional MR imaging is important in the planning of
      stabilizing operations of the cervical spine.

PMID- 9755706
TI  - High-resolution MR imaging of the cutis and subcutis. Histological correlation.
AB  - OBJECTIVE: To determine whether the spatial resolution that can be achieved with
      currently available MR devices is adequate for the evaluation of skin disease.
      MATERIAL AND METHODS: We correlated high-resolution MR images of the skin with
      dermatohistopathology in 26 patients. The examinations were carried out on a 1.0
      T imager using a commercially available surface coil (ID 7.5 cm) and optimized SE
      and GE sequences. Image quality was assessed by four readers on a questionnaire.
      RESULTS: The visualization of the dermis, subcutaneous tissue, and muscle fascia
      allowed a pattern analysis that gave findings identical to those at
      dermatohistopathology. It was possible to distinguish septal from lobular
      panniculitis, and lipatrophia from sclerodermia. Images with contrast media
      infusion were useful in the differential diagnosis. CONCLUSION: High-resolution
      MR imaging may narrow down the differential diagnosis of various skin diseases
      and may help to reduce the number of skin biopsies on certain indications.

PMID- 9755707
TI  - MR appearance of anomalous insertion of the medial meniscus. A case report.
AB  - We report on the MR imaging of an anomalous medial meniscus with a tear in a 41
      year-old man. Anomaly of the medial meniscus is rare and difficult to diagnose
      clinically. The MR images contributed to the pre-arthroscopic diagnosis and
      arthroscopy confirmed the lesion. The anomalous meniscus was not related to the
      symptoms.

PMID- 9755708
TI  - MR and CT cholangiography in evaluation of the biliary tract.
AB  - OBJECTIVE: To compare MR and CT cholangiography (MRC and CTC) in evaluating the
      anatomy of the extrahepatic biliary tract and the pathology related to the
      gallbladder. MATERIAL AND METHODS: Twenty-three patients underwent MRC and CTC
      with a biliary contrast medium for investigation of biliary disease. 3D displays
      of both were also obtained. Endoscopic retrograde cholangiography was performed
      in 17 patients, and the pathology of all 23 was evaluated. RESULTS: Overall, the
      image quality was higher with CTC than with MRC (4.7 vs 3.9, p < 0.05). The
      cystic duct was demonstrated better by CTC than MRC (p < 0.05). Multiplanar
      reformation (MPR) and source images provided additional information to that
      obtained from 3D MRC and CTC images. Gallstones were revealed in 6 patients by
      CTC and in 5 of these 6 by MRC. In 2 patients with cholecystitis, CTC
      demonstrated gallbladder wall thickening but MRC did not. In 3 patients with
      adenomyomatosis. MRC demonstrated Rokitansky-Aschoff sinuses (RAS) while CTC
      demonstrated focal gallbladder wall thickening in all 3 and RAS in 1 of them.
      CONCLUSION: Both MRC and CTC provided anatomical and pathological information
      about the biliary system. With both techniques, however, either MPR or source
      images proved necessary in addition for evaluating the biliary system anatomy and
      pathology. The gallbladder wall was depicted clearly in source CTC, but MRC is
      recommended for the evaluation of adenomyomatosis because it depicts RAS clearly.

PMID- 9755709
TI  - Colour Doppler imaging of shunts from the left portal branch in portal
      hypertension. Description of a typical pattern.
AB  - PURPOSE: To describe the typical colour Doppler appearance of a shunt through the
      parenchyma of the left lobe of the liver in portal hypertension. MATERIAL AND
      METHODS: Ultrasound images of 141 patients with biopsy-verified cirrhosis were
      reviewed. Special note was taken of the appearance of shunts from the left portal
      branch. RESULTS: In 28 patients, shunts from the left portal branch were detected
      ultrasonographically, 10 of which ran through the liver parenchyma on a course
      separated from the ligamentum teres. Seven of these 10 followed a tortuous course
      just below the surface of the liver creating a ball or corkscrew-like pattern.
      CONCLUSION: Shunts from the left portal branch are not uncommon and may represent
      the only ultrasonographically detectable pathology in these patients. Recognition
      of the typical pattern will facilitate their detection.

PMID- 9755710
TI  - The efficacy of FP 736-04 in experimental liver cirrhosis.
AB  - PURPOSE: To determine whether the uptake of FP 736-04, a hepatocyte-specific CT
      contrast agent, is influenced by cirrhotic changes in the liver. MATERIAL AND
      METHODS: Liver cirrhosis was induced by bile duct ligation (BDL) in Sprague
      Dawley rats. Seventy-four animals were divided into three groups comprising: rats
      with acute BDL; rats with chronic BDL; and normal controls. CT was performed
      after i.v. infusion of FP 736-04 or saline at a dose of 2 ml/kg b.w., and the
      mean attenuation in the liver and spleen was measured. The livers from the
      chronic BDL group were taken for histopathological examination and the extent of
      the disease was graded according to an arbitrary scale. RESULTS AND CONCLUSION:
      There was a significant reduction of the native liver attenuation in both chronic
      and acute BDL groups as compared with the normal controls. FP 736-04 was taken up
      by the liver parenchyma with a similar degree of enhancement in all three groups.

PMID- 9755712
TI  - Gadopentetate dimeglumine as a contrast agent in peripheral angioplasty. A case
      report.
AB  - Gadopentetate dimeglumine (Gd-DTPA) is widely used as a contrast agent in MR
      imaging. We report on a case in which Gd-DTPA was used as the contrast agent
      during angioplasty in a patient who had recently had an adverse reaction to a non
      ionic iodinated contrast medium. Gd-DTPA allowed a diagnostic angiogram to be
      performed with no side effects, and may thus be a useful contrast agent at
      angioplasty in patients with contra-indications to iodinated contrast media.

PMID- 9755711
TI  - Changes in tissue oxygen tension caused by contrast media injected into the
      femoral artery of the dog.
AB  - PURPOSE: To document changes in tissue oxygen tension as measured directly in an
      area perfused with contrast medium. MATERIAL AND METHODS: Changes in tissue
      oxygen tension in response to the injection of ionic and non-ionic contrast media
      into the femoral arteries were measured in the femoral adductor (proximal) and
      gastrocnemius (distal) muscles of 8 dogs. Amidotrizoic-acid and iopamidol were
      injected in two different iodine concentrations (370 mg I/ml and 185 mg I/ml
      respectively) and tissue oxygen tension in the proximal and distal muscles was
      monitored continuously using polarographic needle electrodes. RESULTS AND
      CONCLUSION: A transient decrease and subsequent increase of muscle tissue oxygen
      tension were observed after the injection. The extent of these changes depended
      on the concentration and osmolality of the medium. To minimize changes in
      peripheral tissue oxygen tension, contrast media with low osmolality and low
      concentration are recommended for femoral angiography.

PMID- 9755713
TI  - Correlation between dose rate and T1 in blood at Gd-enhanced MR angiography.
AB  - PURPOSE: To determine the correlation between dose rate and T1 in blood at Gd
      enhanced MR angiography (MRA). MATERIAL AND METHODS: A test dose of contrast
      agent was used to calculate the time delay between injection and arrival in the
      abdominal aorta. The dose rate was expressed as ml.kg b.w.-1.s-1. The correlation
      between dose rate and T1 was determined by varying the dose rate while keeping
      the scanning and infusion times constant. The signal intensity in the abdominal
      aorta was measured during the first pass of Gd and compared with markers of known
      T1 values. RESULTS: A correlation between dose rate and T1 in blood was obtained.
      CONCLUSION: A Gd dose rate of 0.01 ml.kg b.w.-1.s-1 gives a T1 in blood of 100
      ms. This can be used to calculate the optimal pulse sequence for contrast
      enhanced MRA.

PMID- 9755714
TI  - Testicular microlithiasis--a possibly premalignant condition. Report of five
      cases and a review of the literature.
AB  - Testicular microlithiasis (TM) is a rare condition characterized by the presence
      of multiple small intratesticular calcifications. The etiology is unknown but the
      condition has been observed in a variety of different urological conditions. We
      report on 5 cases diagnosed by ultrasonography at our departments from 1992 to
      1994. A review of the literature plus our present 5 cases gives a total of 124
      reported cases of TM. TM was associated with testicular malignancy in 44 patients
      (35%) of whom 24 (19%) had a seminoma and 20 (16%) a non-seminoma. There were 4
      reports of testicular malignancy developing in patients with a prior diagnosis of
      TM. The condition should be considered premalignant and a careful follow-up of TM
      patients is advocated.

PMID- 9755715
TI  - Atypical CT findings of cervical lymphadenopathy due to Hodgkin's disease. A case
      report.
AB  - We describe a case of Hodgkin's disease with cervical lymphadenopathy which may
      easily be confused with a granulomatous process both radiologically and
      pathologically.

PMID- 9755716
TI  - Bioreductive drugs into the next millennium.

PMID- 9755717
TI  - Tirapazamine: laboratory data relevant to clinical activity.
AB  - Tirapazamine (TPZ, SR 4233, WIN 59075, 3-amino-1,2,4-benzotriazine 1,4-dioxide,
      Tirazone) is the lead compound in the benzotriazine di-N-oxide class of
      bioreductive anticancer agents. Extensive preclinical testing has established
      that the mechanism for the selective toxicity towards hypoxic cells is the result
      of a one-electron reduction of the parent molecule to a free radical species that
      interacts with DNA to produce single- and double-strand breaks and lethal
      chromosome aberrations. It has also shown activity when combined with
      fractionated irradiation and when combined with some chemotherapy agents,
      particularly cisplatin and carboplatin. In this review we address those questions
      about the drug that are most relevance to the clinical use of the compound. In
      particular we review the evidence for the mechanism of action of the drug, and
      also show that a large portion of the synergy seen in experimental tumors when
      TPZ is combined with cisplatin is the result of a cellular interaction between
      TPZ and cisplatin that depends on hypoxia. Also of relevance to clinical use is
      whether the toxicity of TPZ is cumulative such as occurs with nitroimidazoles,
      another class of hypoxia-activated agents. Such cumulative toxicity is not
      evident. Finally, we present an analysis based on the area under the curve for
      mice and humans that demonstrates that the doses being used in current Phase II
      radiotherapy protocols and Phase III chemotherapy protocols should be sufficient
      to produce clinical activity. We conclude that the preclinical data suggest that
      it is likely that TPZ will be active in the clinic, particularly when combined
      with cisplatin.

PMID- 9755718
TI  - Enzymology of tirapazamine metabolism: a review.
AB  - The enzymology of triapazamine (TPZ, SR 4233, WIN 59075, 3-amino-1,2,4
      benzotriazene 1,4-dioxide, Tirazone) has been extensively studied in rodents and
      to a lesser extent in human systems. While it is clear that the initial reductive
      step in TPZ activation is enzyme-mediated, there is limited consensus in the
      published literature as to the relative contributions of the cellular reductases
      involved. Moreover, not only is the importance of subcellular localization for
      these putative activating reductase(s) far from clear, but their activity
      profiles in vivo are poorly defined. The same might also be said of the potential
      detoxifying enzymes. This review will attempt to establish what common ground
      exists regarding the enzymology of TPZ metabolism, and will relate the available
      evidence to the enzyme profiles found in human cell lines in vitro, as well as in
      xenograft models and human solid tumours.

PMID- 9755719
TI  - 1,2,4-Benzotriazine 1,4-dioxides. An important class of hypoxic cytotoxins with
      antitumor activity.
AB  - Tirapazamine (1,2,4-benzotriazin-3-amine 1,4-dioxide, SR 4233, WIN 59075) is the
      lead compound representing this class of anticancer drugs. It is also the first
      compound to be introduced in the clinic as a pure bioreductive cytotoxic agent.
      Tirapazamine represents a completely novel approach to the treatment of solid
      tumors and has generated considerable interest, with research being carried out
      on all aspects of the its anticancer activity. Phase III trials of tirapazamine
      in combination with cisplatin (cDDP) have recently been concluded, and phase II
      trials of triapazamine in combination with irradiation are presently being
      performed. We developed a drug discovery program into this class of compounds
      designed to produce derivatives with improved in vivo activity against solid
      tumors. Based on the hypothesis that these compounds require bioreductive
      activation for antitumor activity, the research was primarily directed at
      producing analogues with greater electron affinity and improved aqueous
      solubility. The in vitro and in vivo data for a variety of structural analogues
      clearly show that 1,2,4-benzotriazine 1,4-dioxides have considerable potential as
      anticancer agents. When their activity is compared directly with the activity
      observed for triapazamine, the most promising series of analogues appears to be
      the 3-alkyl-substituted derivatives, especially the 3-ethyl- and 3-(2'
      methoxyethyl)-derivatives, SR 4895 and SR 4941 respectively.

PMID- 9755720
TI  - Targeting hypoxia with a new generation of indolequinones.
AB  - The indolequinone class of bioreductive alkylating agents has been developed to
      effectively target the hypoxic cell population of the tumour. The mechanism of
      activation of these prodrugs relies initially on the reduction of the p-quinonoid
      moiety utilizing reductive enzymes to form electrophilic sites which can be
      attacked by DNA to promote cell kill. Minor structural changes of the indole
      'nucleus' may result in substantial favourable pharmacological and physiological
      changes. Investigation of the mode of action of these compounds has resulted in
      the use of novel indolequinones as 'trigger' molecules that can efficiently
      release secondary agents into the hypoxic site of action.

PMID- 9755721
TI  - Cyclopropyl indolequinones: mechanistic probes for bioreductive anticancer drug
      action.
AB  - A series of cyclopropyl indolequinones based on structures 5-7 was designed and
      synthesized to probe the structural features essential for bioreductive
      cytotoxicity. Ring opening of the cyclopropane ring under radical conditions was
      demonstrated to be mechanistically feasible, and related to the involvement of
      such one-electron processes in the cytotoxicity of cyclopropyl indolequinones
      under hypoxic conditions.

PMID- 9755722
TI  - Indolequinone bioreductive drugs: kinetic factors which influence selectivity for
      hypoxia.
AB  - The factors influencing the kinetics of the oxygen-sensitive reduction of
      indolequinones, including those bearing leaving groups in the (indol-3-yl)methyl
      position, have been studied. The hydroquinones derived from some representative
      indolequinones were found to autoxidize slowly in oxygenated solution at rates
      (effective rate constant with O2 approximately 40-300 M-1 s-1) that cannot
      compete with the reductive elimination of leaving groups. The rates of reaction
      between hydroquinone and O2 were even slower in the presence of approximately 4
      microM superoxide dismutase (effective rate constant approximately 2-7 M-1 s-1),
      indicating the role of superoxide radicals in hydroquinone autoxidation. Since
      the release of the leaving groups from the hydroquinones is not significantly
      oxygen-sensitive, tumour selectivity requires specific reduction by enzymes that
      are overexpressed in some tumours. Conversely, the release of leaving groups from
      semiquinone radicals is inhibited by oxygen too efficiently unless the
      semiquinone reacts with targets on a timescale of milliseconds. Modification of
      redox properties has been explored with the aim of changing this oxygen
      sensitivity. The new 2-phenylindolequinones are approximately 60-100 mV higher in
      reduction potential than 2-alkyl derivatives but this is insufficient to decrease
      the rate of electron transfer from semiquinone to oxygen to a degree which might
      confer hypoxia-selective cytotoxicity. These results are discussed in the context
      of toxicity of EO9 and related compounds towards hypoxic rather than anoxic
      cells.

PMID- 9755723
TI  - The 5-nitrofuran-2-ylmethylidene group as a potential bioreductively activated
      prodrug system for diol-containing drugs.
AB  - Acid-catalysed condensation of 5-nitrofuran-2-carboxaldehyde with 1-phenylethane
      1,2-diol and with 2,2-dimethyl-1-phenylproane-1,3-diol in boiling benzene gave
      the expected cyclic nitrofuranyl acetals. Biomimetic reduction of these acetals
      with sodium borohydride in the presence of palladium triggered release of the
      parent diols. Thus these nitrofuran acetals may have potential for applications
      as prodrugs for selective release of diol-containing drugs in hypoxic solid
      tumours.

PMID- 9755724
TI  - Radiation-activated prodrugs as hypoxia-selective cytotoxins: model studies with
      nitroarylmethyl quaternary salts.
AB  - Bioreductive drugs are designed to be activated by enzymatic reduction in hypoxic
      regions of tumours, but activation of these drugs is not always fully suppressed
      by oxygen in normal tissues. A further limitation is that bioreductive drug
      activation depends on suitable reductases being expressed in the hypoxic zone.
      This essay proposes an alternative approach in which prodrugs are reduced, and
      thereby activated, in hypoxic regions by ionizing radiation rather than by
      enzymes. This strategy is theoretically attractive, but design requirements for
      such radiation-activated cytotoxins are challenging. In particular, the reducing
      capacity of radiation at clinically relevant doses is small, which necessitates
      the development of prodrugs capable of releasing very potent cytotoxins
      efficiently in hypoxic tissue. It is shown that nitroarylmethyl quaternary (NMQ)
      salts possess many of the features required of a radiation-activated prodrug. In
      some heterocyclic NMQ compounds the cytotoxicity of the latent cytotoxic amine
      effector is suppressed by > 100-fold in the prodrug form, and the effector is
      released rapidly by fragmentation following reduction by a single electron.
      Appreciable cytotoxic activation of NMQ prodrugs can be achieved by irradiation
      at clinically relevant doses in anoxic plasma. Some of the further drug design
      challenges required to develop a clinical agent based on this approach are
      outlined.

PMID- 9755725
TI  - Use of 2-nitroimidazoles as bioreductive markers for tumour hypoxia.
AB  - Tumour hypoxia is thought to contribute to some failures of radiotherapy to
      achieve local control. Polarographic measurements of tumour oxygenation have been
      shown to predict clinical response to radiotherapy and patient survival. Hypoxia
      is also involved in many common types of normal tissue morbidity. However, at
      present there is no widely used method of measuring hypoxia in the clinic, or for
      individualizing therapy on the basis of tumour or tissue oxygenation. The
      bioreductive metabolism of 2-nitroimidazoles provides a way of labelling hypoxic
      cells in vivo and a variety of isotopic labels have been proposed for the non
      invasive detection of bound metabolites of these markers. Several 2
      nitroimidazoles with immunologically identifiable side-chains have been described
      and conventional immunostaining procedures can be used to locate their
      metabolites, bound to hypoxic cells in histological sections. Use of fluorescent
      immunoreagents allows flow cytometric assessment of hypoxia and multiple colour
      fluorescent staining allows hypoxia to be correlated with other markers on a cell
      by cell basis. 2-Nitroimidazole hypoxia markers show considerable promise for
      clinical use in diagnosing hypoxia and their use could allow rational application
      of hypoxia-related therapies to those patients most likely to benefit from them.

PMID- 9755726
TI  - Preclinical development and current status of the fluorinated 2-nitroimidazole
      hypoxia probe N-(2-hydroxy-3,3,3-trifluoropropyl)-2-(2-nitro-1-imidazolyl)
      acetamide (SR 4554, CRC 94/17): a non-invasive diagnostic probe for the
      measurement of tumor hypoxia by magnetic resonance spectroscopy and imaging, and
      by positron emission tomography.
AB  - Hypoxia occurs to a variable extent in a vast majority of rodent and human solid
      tumors. It results from an inadequate and disorganized tumor vasculature, and
      hence an impaired oxygen delivery. A probe for the non-invasive detection of
      tumor hypoxia could find important utility in the selection of patients for
      therapy with bioreductive agents, anti-angiogenic/anti-vascular therapies and
      hypoxia-targeted gene therapy. In addition, tumor hypoxia has been shown to
      predict for treatment outcome following radio- or chemotherapy in human cancers,
      the underlying mechanism for which may involve hypoxia driving genetic
      instability and resulting tumor progression. Beyond oncology, utility can also be
      envisaged in stroke, ischemic heart disease, peripheral vascular disease,
      arthritis and other disorders. Design, validation, preclinical development and
      current status of a fluorinated 2-nitroimidazole, N-(2-hydroxy-3,3,3
      trifluoropropyl)-2-(2-nitro-l-imidazolyl) acetamide (SR 4554, CRC 94/17), which
      has been rationally designed for the measurement of tumor hypoxia by magnetic
      resonance spectroscopy (MRS) and imaging (MRI), are reviewed. Application in
      positron emission tomography (PET) detection is also proposed. Design goals were:
      (i) a nitro group with appropriate redox potential for selective reduction and
      binding in hypoxic tumor cells; (ii) hydrophilic/hydrogen bonding character in
      the side chain to limit nervous tissue penetration and prevent neurotoxicity; and
      (iii) three equivalent fluorine atoms to enhance MRS/MRI detection, located in a
      metabolically stable position. Reduction of SR 4554 by mouse liver microsomes was
      dependent on oxygen content, with a half-maximal inhibition at 0.48 +/- 0.06%. SR
      4554 underwent nitroreduction by hypoxic but not oxic tumor cells in vitro and
      electron energy loss spectroscopic analysis showed selective retention in the
      hypoxic regions of multicellular tumor spheroids. Pharmacokinetic design goals
      were met. In particular, low brain tissue concentrations were seen in contrast to
      excellent tumor levels, as measured by high performance liquid chromatography.
      The extent of this restricted entry to brain tumor was surprising given the
      overall octanol/water partition coefficient and was attributed to the
      hydrophilic/hydrogen bonding character of the side chain. Quantitative MRS was
      used to assess the retention of 19F signal in murine tumors and human tumor
      xenografts. The 19F retention index (FRI; ratio of 19F signal levels at 6 h
      relative to that at 45 min) ranged from 0.5 to 1.0 and 0.2 to 0.9 for murine
      tumors and human xenografts respectively. The correlation between SR 4554
      retention and pO2 was not a linear one, but when FRI was > 0.5, the % pO2 < or =
      5 mmHg was always > 60%, indicating that high FRI was associated with low levels
      of oxygenation. Finally, whole body 19F-MRI in mice demonstrated that SR 4554 and
      related metabolites localized mainly in tumor, liver and bladder regions. A
      selective MRS signal was readily detectable in tumors at doses at least 7-fold
      lower than those likely to cause toxicity in mice. We conclude that proof of
      principle is established for the use of SR 4554 as a non-invasive MRS/MRI probe
      for the detection of tumor hypoxia. Based on these promising studies, SR 4554 has
      been selected for clinical development.

PMID- 9755727
TI  - Altered efficacy and selectivity of tyrosine kinase inhibitors of the activated
      states of protein tyrosine kinases.

PMID- 9755728
TI  - Picture of the month. Cutaneous larva migrans (creeping eruption).

PMID- 9755729
TI  - Change in coronary risk factor levels in couples after lifestyle intervention.

PMID- 9755730
TI  - Chiropractic: a fantasy and delusion.

PMID- 9755731
TI  - Assessing quality of care via HEDIS 3.0. Is there a better way?
AB  - Patients, employers, and third-party payers are all calling for improved measures
      of health care quality. This has led to the development of "report cards,"
      assessments that are many times applied not just to health plans but also to
      providers. One attempt at creating a standardized set of quality and
      effectiveness measures is the Health Plan Employer Data and Information Set
      (HEDIS). The HEDIS measures are based primarily on analyses of administrative
      data sets. Problems with HEDIS measures, including the probability that plans
      will use different data collection methods and a lack of risk adjustment, may
      result in incorrect conclusions about the quality of care delivered by various
      providers. An alternative method of standardized surveys is proposed that will
      overcome many of the limitations of the current HEDIS measures, provide outcome
      rather than process data, and provide data for developing interventions to
      improve quality.

PMID- 9755732
TI  - Measuring the health of seniors.

PMID- 9755733
TI  - The patient self-determination act and advance directive completion in nursing
      homes.
AB  - OBJECTIVES: To assess the prevalence of advance directives among nursing home
      residents before and after passage of the Patient Self-Determination Act (PSDA)
      and to identify factors associated with advance directive completion. DESIGN:
      Prestudy and poststudy nursing home admissions using medical record reviews and a
      companion cross-sectional survey of alert and oriented residents. SETTING: Six
      nursing homes in Connecticut. PARTICIPANTS: Residents (N = 635) from 6 randomly
      chosen nursing homes in the greater Hartford and greater New Haven areas. MAIN
      OUTCOME MEASURES: The existence of a documented advance directive, the timing of
      advance directive completion, and reported reasons for completion and
      noncompletion. RESULTS: The prevalence of advance directives documentation in
      nursing home medical records has increased significantly since the implementation
      of the PSDA (4.7% [14/300] before vs 34.7% [104/300] after PSDA; odds ratio,
      10.84; P < .001). The increase in documented advance directives was significant
      after controlling for sociodemographic and health status factors (odds ratio,
      11.5; P < .001). Residents admitted to the nursing homes from hospitals (vs from
      their home or other source), residents with more education, and residents paying
      privately for nursing home care (vs using Medicare or Medicaid benefits) were
      more likely to have documented advance directives. Younger residents (aged < 75
      years) were less likely than older residents to have completed a directive. Among
      the 35 interviewed residents, the most common reason for completing an advance
      directive was experience with a prolonged death of a friend or family member.
      Only 1 of the interviewed residents reported that the information provided under
      the PSDA at the time of admission was an important factor in choosing to complete
      an advance directive. CONCLUSIONS: Nearly 35% of the residents in the post PSDA
      cohort had an advance directive documented in the medical record. Most residents
      with advance directives had completed them more than 6 months before the nursing
      home admission. The major effect of the PSDA for nursing homes has been to
      enhance the documentation of existing advance directives. Little evidence exists
      that providing advance directive information at the time of nursing home
      admission has enhanced the completion of an advance directive after admission.

PMID- 9755734
TI  - Transdermal nicotine therapy and primary care. Importance of counseling,
      demographic, and participant selection factors on 1-year quit rates. The Nebraska
      Primary Practice Smoking Cessation Trial Group.
AB  - OBJECTIVE: To evaluate the smoking cessation efficacy of nicotine patch therapy
      as an adjunct to low-intensity, primary care intervention. DESIGN: Randomized,
      placebo-controlled, double-blind, multisite trial. SETTINGS: Twenty-one primary
      care sites in Nebraska. PATIENTS: A total of 369 smokers of 20 or more cigarettes
      per day. INTERVENTION: Two brief primary care visits for smoking intervention
      with 10 weeks of active or placebo-patch therapy. MAIN OUTCOME MEASURES:
      Confirmed self-reported abstinence 3, 6, and 12 months after the quit day.
      RESULTS: Compared with placebo control subjects, participants assigned nicotine
      patches had higher 3-month (23.4% vs 11.4%; P < .01) and 6-month (18.5% vs 10.3%;
      P < .05) abstinence rates. The 1-year abstinence rates for the active and placebo
      patch groups were 14.7% and 8.7%, respectively (P = .07). Of smokers aged 45
      years and older, 9 (18.8%) of 48 using active patches compared with 0 of 31 using
      placebo patches achieved 12-month abstinence (chi 2 = 6.56; P < .05). Among those
      with high nicotine dependency scores (Fagerstrom score > or = 7), 1-year
      abstinence rates were significantly higher in the nicotine patch group (19.1%)
      compared with the placebo group (5.0%) (chi 2 = 10.7; P = .001). However, there
      was no significant difference in 1-year quit rates for participants with low
      Fagerstrom scores (< 7). CONCLUSIONS: Nicotine patch therapy enhanced 6 month
      quit rates as an adjunct to brief primary care intervention. The highest quit
      rates were achieved by participants who specifically contacted the site to enroll
      in the study or to obtain a prescription for nicotine patches. Differences in
      participant selection factors may account, in part, for the lower smoking
      cessation rates associated with primary care intervention. Duration of
      counseling, patient age, and Fagerstrom scores may be important factors related
      to the long-term smoking cessation success of nicotine patch therapy.

PMID- 9755735
TI  - Religious beliefs and practices in family medicine.
AB  - OBJECTIVES: To determine whether the religious beliefs and behaviors of family
      medicine outpatients differed from those of their physicians and whether
      patients' religiousness affects their expectations of their physicians regarding
      religious matters. DESIGN: A survey study was performed on a consecutive sample
      of 380 family medicine clinic outpatients and 31 family medicine faculty and
      residents in 2 family medicine residency programs. SETTING AND SUBJECTS:
      Outpatients were recruited from an outpatient clinic of a family medicine
      residency program in North Carolina. Family medicine physicians and residents
      were recruited from this program and another in Texas. MAIN OUTCOME MEASURES:
      Scores were obtained from the Springfield Religiosity Scale, the Hoge Intrinsic
      Religiosity Scale, and a religious beliefs questionnaire designed for this study.
      RESULTS: Absence of religious affiliation was more common for physicians than
      patients. Physicians were less likely than patients to pray privately and less
      likely to hold intrinsic religious attitudes. Patients were more likely than
      physicians to be interested in their own physician's religious beliefs, more
      likely to feel that they should know their physician's religious beliefs, and
      more likely to want their physician to pray with them under certain
      circumstances. When sex and age were controlled, some of these differences
      disappeared. When compared with patients, physicians tended to be younger and
      male--characteristics inversely associated with religious belief and practice.
      Regardless of sex or age, however, the more religious the patients, the more
      likely the desire to know their physician's religious beliefs and share their own
      religious beliefs. CONCLUSIONS: Patients are more involved in religious beliefs
      and practices than physicians, a finding partially explained by age and sex. The
      more religious the patients, the more important it is for them to know their
      physician's beliefs, share their beliefs with their physician, and want their
      physicians to pray with them.

PMID- 9755736
TI  - Knowledge of periconceptional folic acid for the prevention of neural tube
      defects. The missing links. Northeastern Ontario Primary Care Research Group.
AB  - BACKGROUND: Periconceptional folic acid supplementation is effective in
      preventing primary and secondary neural tube defects (NTDs) and other congenital
      defects. However, debate exists regarding the effectiveness of public and
      physician education on patient knowledge and compliance. OBJECTIVE: To examine
      the level of knowledge about the usefulness of periconceptional folic acid
      supplementation in a sample of patients from primary care practices. DESIGN:
      Cross-sectional survey. A confidential, anonymous questionnaire was completed by
      patients before physician encounters. A maximum of 20 consecutive female patients
      from each of 3 age groups (16-24, 25-32, and 33-40 years) were recruited from
      each primary care practice. SETTINGS: Twenty-two Canadian teaching practices
      affiliated with the Northeastern Ontario Primary Care Research Group. OUTCOME:
      Women's knowledge of periconceptional folic acid supplementation for the
      prevention of NTDs. RESULTS: Of 1125 eligible female patients between the ages of
      16 and 40 years visiting their family physician in 1996, 1124 (99.9%) completed
      the questionnaire. General awareness of NTDs was high (62.7%); however, knowledge
      that these defects were preventable was lower (22.5%). Only 7.8% of the women
      made the association between folic acid intake and NTDs. The specific knowledge
      that NTDs could be prevented with folic acid supplementation before conception
      was identified by 1.8% of the sample. Pregnant participants were at least twice
      as likely to be informed about the link. Interpractice variability existed with
      respect to knowledge of folic acid supplementation. CONCLUSION: Knowledge of
      periconceptional folic acid supplementation for the prevention of NTDs was low in
      this sample and is likely to be reflected in missed opportunities to prevent an
      important class of congenital malformations.

PMID- 9755737
TI  - Relapse of depression in primary care. Rate and clinical predictors.
AB  - OBJECTIVE: To determine the clinical predictors and rate of relapse for major
      depression in primary care. DESIGN: A cohort study of subjects in 2 randomized
      trials of depressed patients diagnosed and prescribed antidepressant medicine by
      primary care physicians. Baseline, 7-month, and 19-month assessments were
      conducted. SETTING: A large primary care clinic of a staff-model health
      maintenance organization. PATIENTS: Two hundred fifty-one primary care patients
      who did not satisfy Diagnostic and Statistical Manual of Mental Disorders,
      Revised Third Edition (DSM-III-R) criteria for major depression at 7 months. MAIN
      OUTCOME MEASURES: Relapse was defined as (1) satisfying DSM-III-R criteria for
      major depression at 19 months, or (2) reporting an interval episode of 2 weeks or
      more of depressed mood and symptoms between 7 and 19 months. Predictors examined
      included demographic characteristics, medical comorbidity, disability, and
      psychological symptoms. Depressive symptoms were measured by Inventory of
      Depressive Symptoms and Hopkins Symptoms Checklist. RESULTS: Of the patients,
      37.1% reported relapse of depression in the 12-month relapse-risk period. The 2
      major risk factors associated with relapse were (1) persistence of subthreshold
      depressive symptoms 7 months after the initiation of antidepressant therapy (odds
      ratio, 3.3; 95% confidence interval, 2.74-3.93) and (2) history of 2 or more
      episodes of major depression, or chronic mood symptoms for 2 years (odds ratio,
      2.1; 95% confidence interval, 1.41-2.76). Patients with both risk factors were
      approximately 3 times more likely to relapse than patients with neither.
      CONCLUSIONS: The relapse rate among primary care patients treated for depression
      approached that of specialty samples, with more than one third reporting relapse
      in 1 year. Clinical characteristics can help target high-risk patients for
      relapse prevention efforts.

PMID- 9755738
TI  - False positives, false negatives, and the validity of the diagnosis of major
      depression in primary care.
AB  - OBJECTIVE: To explore the issues of diagnostic specificity and psychiatric
      "caseness" (i.e., whether a patient meets the conditions to qualify as a "case"
      of a disease or syndrome) for major depression in the primary care setting.
      DESIGN: A cross-sectional study comparing the demographic, clinical, and mental
      health characteristics of patients identified as depressed by their family
      physicians with those meeting diagnostic criteria for major depression on the
      criterion standard Structured Clinical Interview for Diagnostic and Statistical
      Manual of Mental Disorders, Revised Third Edition. SETTING: The offices of 50
      family physicians from private and academic practice in southeast Michigan.
      PATIENTS: A total of 1580 consecutive adult patients being seen for routine
      primary care services, from whom a weighted sample of 372 patients completed a
      set of mental health screening and diagnostic instruments. MAIN OUTCOME MEASURES:
      Patients were assigned to 1 of 4 groups (true positive, false positive, false
      negative, and true negative) based on clinician identification and Structured
      Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders,
      Revised Third Edition diagnosis. Differences between the 4 groups in demographic
      and clinical characteristics, scores on mental health instruments and mental
      health history were explored. RESULTS: Physician identification of depression was
      strongly associated with increased familiarity with the patient and the presence
      of suggestive clinical cues, such as history of or treatment for depression,
      patient distress, and presence of vegetative symptoms. Patients in the false
      positive group displayed significantly higher levels of distress and impairment
      and were significantly more likely to have a history of mental health problems
      and treatment than were those in the true-negative group. The 2 "misidentified"
      groups, false positives and false negatives, were indistinguishable in their
      clinical characteristics (impairment, distress, or mental health history). Both
      groups' scores occupied the middle ground between true positives and true
      negatives on most clinical characteristics. Physicians appeared to discriminate
      between these 2 groups on the basis of their knowledge of the patient's clinical
      history. CONCLUSIONS: Misidentification of depression in primary care may be in
      part an artifact of the use of the psychiatric model of caseness in the primary
      care setting. Our results are most consistent with a chronic disease-based model
      of depressive disorder, in which patients classified as false positive and false
      negative occupy a clinical middle ground between clearly depressed and clearly
      nondepressed patients. Family physicians appear to respond to meaningful clinical
      cues in assigning the diagnosis of depression to these distressed and impaired
      patients.

PMID- 9755739
TI  - Managing our depressed patients. Gold standards vs higher standards.

PMID- 9755740
TI  - Diagnostic efficiency of home pregnancy test kits. A meta-analysis.
AB  - OBJECTIVE: To assess the diagnostic efficiency of home pregnancy test (HPT) kits.
      DATA SOURCES: A literature search of English-language studies was performed with
      MEDLINE and a review of bibliographies. STUDY SELECTION: Studies were included if
      HPT kits were compared with a criterion standard (laboratory testing), if they
      used appropriate controls, and if data were available to determine sensitivity
      and specificity. DATA EXTRACTION: Two investigators independently extracted data,
      and disagreement was resolved by consensus. Sensitivity, specificity, and an
      effectiveness score (a measure of the discriminatory power of the test, with
      higher scores implying greater effectiveness) were calculated. DATA SYNTHESIS:
      Five studies evaluating 16 HPT kits met the inclusion criteria. The range of
      sensitivities for HPT kits was 0.52 to 1.0. In studies where urine samples
      obtained by the investigators were tested by volunteers, sensitivity was 0.91
      (95% confidence interval [CI], 0.84-0.96). However, the sensitivity was less in
      studies where subjects were actual patients who performed the test on their own
      urine samples (sensitivity, 0.75 [95% CI, 0.64-0.85]). The test effectiveness
      score was 2.75 (95% CI, 2.3-3.2) for studies where subjects were volunteers but
      deteriorated to 0.82 (95% CI, 0.4-1.2) for studies with actual patients.
      CONCLUSIONS: The diagnostic efficiency of HPT kits is greatly affected by
      characteristics of the users. Despite the popularity of these kits, the
      relatively low effectiveness scores of these kits when used by actual patients
      are of concern. We suggest that manufacturers of HPT kits publish results of
      trials in actual patients before marketing them to the general public.

PMID- 9755741
TI  - Are serotonin uptake inhibitors useful in chronic pain syndromes such as
      fibromyalgia or diabetic neuropathy?

PMID- 9755742
TI  - Narcolepsy. Signs, symptoms, differential diagnosis, and management.
AB  - Narcolepsy is a chronic neurologic disorder characterized by excessive daytime
      sleepiness and cataplexy and less often by hypnagogic hallucinations and sleep
      paralysis. While patients report excessive daytime sleepiness and cataplexy as
      the more frequent symptoms of this condition, excessive daytime sleepiness is
      generally believed to be the most debilitating. Narcolepsy often is undiagnosed
      or misdiagnosed for a variety of reasons. Although confirmation of an initial
      diagnosis requires monitoring of physiologic variables conducted at a sleep
      center by specialists, the primary care physician has a critical role in the
      identification and management of this incurable affliction. This article provides
      recommendations for the diagnosis and management of narcolepsy. The cataplexy
      associated with narcolepsy can be managed with tricyclic antidepressants. The
      excessive sleepiness is managed with stimulants but newer agents, such as
      modafinil, which will be marketed as Provigil, and selegiline hydrochloride, with
      fewer adverse effects and less abuse potential, may offer means of promoting
      daytime wakefulness. Groups such as the National Sleep Foundation, Washington,
      DC, and the Narcolepsy Network, Cincinnati, Ohio, can provide patients with
      needed support and information.

PMID- 9755743
TI  - Use of a structured encounter form to improve well-child care documentation.
AB  - OBJECTIVE: To determine if a structured encounter form for well-child care
      improves documentation of well-child care. DESIGN: Retrospective medical record
      review of a before-and-after trial. SETTING: Family practice residency clinic
      serving a primarily low-socioeconomic urban population. PATIENTS: Children
      younger than 6 years receiving well-child care visits. INTERVENTION: Detailed
      checklists were developed and implemented in 1994 for each of 12 well-child
      examinations for the assessment of children aged 2 weeks to 5 years based on
      recommendations from the American Academy of Pediatrics and the US Preventive
      Services Task Force. MAIN OUTCOME MEASURES: Documentation of multiple aspects of
      well-child care, including developmental assessment, safety and nutrition
      counseling, and laboratory tests for 6-month periods in 1993 and 1994, before and
      after implementation of the structured encounter form. RESULTS: A total of 842
      well-child visits were reviewed. Documentation improved significantly with the
      use of the encounter form for 19 of the 23 aspects of well-child care that were
      studied. Screening test rates were less than optimal despite the encounter form.
      CONCLUSIONS: The structured encounter form was very effective in improving
      documentation of almost all aspects of well-child care. However, effective
      communication is needed among physicians, nurses, and parents to ensure optimal
      screening test rates.

PMID- 9755744
TI  - Elderly patients' preferences for long-term life support.
AB  - OBJECTIVE: To study elderly patients' preferences regarding mechanical
      ventilation and tube feeding and to compare their preferences for short-term use
      with their preferences for long-term use of these life support interventions.
      DESIGN: Interviews with patients by clinicians during routine office visits.
      SETTING: Hospital-based, primary care geriatrics clinic in downtown Denver, Colo.
      PATIENTS: Two hundred eighty-seven elderly persons (mean age, 77 years; range, 60
      99 years). MAIN OUTCOME MEASURES: Preferences to use or withhold: (1) short-term
      mechanical ventilation; (2) long-term mechanical ventilation; (3) short-term tube
      feeding; and (4) long-term tube feeding. RESULTS: Of the total sample, 253
      patients (88%) would prefer short-term mechanical ventilation if the chance of
      recovering was reasonably good but only 11 (3.5%) would prefer long-term
      mechanical ventilation. One hundred eighty-nine (65%) would prefer short-term
      tube feeding, but only 13 (4.5%) would prefer long-term tube feeding in the
      setting of significant cognitive impairment. CONCLUSIONS: Most elderly persons
      opt for short-term mechanical ventilation or tube feeding if the chance of
      recovering is reasonably good. Only a small minority would opt for long-term
      mechanical ventilation or tube feeding.

PMID- 9755745
TI  - One more test.

PMID- 9755746
TI  - [Role of intravascular brachytherapy in the prevention of vascular restenosis
      after angioplasty].
AB  - About 30% of patients who underwent percutaneous transluminal coronary
      angioplasty show evidence of restenosis, which appears to be independent of the
      angioplasty method used. The restenosis is due of two factors, firstly migration
      of smooth vascular muscle cells of the vascular media to the intima and
      multiplication which lead to the formation of a neo-intima. Irradiation limits
      the proliferation by acting of the cells in the mitotic stage. The vascular
      target volume is not very thick and is difficult to define it, that why
      brachytherapy seems to be the best procedure to prevent restenosis. However, the
      development of this treatment present many difficulties. Different irradiation
      techniques have been studied. Such techniques include catheter containing
      radioactive sealed source, radioactive stent, or balloon containing radioactive
      liquid inside. Each of these methods have their own advantages, inconveniences,
      problems and risks. Radioisotope may be either beta or gamma emitters. Gamma
      emitter presents problems for radioprotection but the satisfactory dose
      distribution may be difficult to obtain using beta emitter. Choice of dose, dose
      rate and delay between the end of angioplasty and the beginning of brachytherapy
      is subject to some discuss. Animal experiments using radioisotope have shown
      reduction in cell proliferation. Human trials showed feasibility, safety of the
      method and real impact on restenosis prevention. However, long-term efficacy has
      not been proved because the follow-up of the patients is too short. A randomized
      trial of 192Ir brachytherapy for prevention of restenosis has recently shown the
      efficacy in short and median term. However, long term efficiency and secondary
      effects have not yet been established as the follow up time of this study is
      still too short. That is why, collaboration between cardiologists and
      radiotherapists and physicists is indispensable to enable the development of an
      optimal technique.

PMID- 9755747
TI  - [Radiotherapy of stage T1-T2 M0 prostatic adenocarcinoma. Analysis of the
      carcinologic results of a multicenter study of 610 patients. Groupe Radiotherapie
      de la Commission de Cooperation Medicale Intercentres (CCMI)].
AB  - PURPOSE: Retrospective analysis of the results of radiotherapy in localized
      prostatic adenocarcinoma. Complications were excluded. PATIENTS AND METHODS: Six
      hundred-and-ten T1-T2 adenocarcinomas of the prostate were treated with
      continuous courses of external beam radiation therapy in 19 participating
      Institutes between January 1983 and January 1988. The mean follow-up was 10.4
      years; the mean age of patients at the beginning of radiotherapy was 68.5 years.
      RESULTS: A 10-year, local control had been achieved in 86% of T1-T2 (81.4% for
      T2). The 5- and 10-year metastatic relapse rates were 25.3% and 30% (29% and
      38.1% for T2), respectively. At 10 years, 62.4% of T1-T2 were recurrence-free;
      overall survival rate was 45.8% and cause-specific survival rate was 70.5%; 29.9%
      of T1-T2 patients were alive and disease-free. T category (TNM), pathologic
      grade, pelvic lymph node status, local tumor control, and obstructive ureteral
      symptoms were correlated with survival. The influence of pelvic nodes radiation,
      dose, overall treatment time, previous endocrine treatment, and transuretral
      resection was not significant for disease-free survival (alive and disease-free)
      and other endpoints. CONCLUSION: There was no difference between the French
      series (1975-1982 and 1983-1988). The results of the literature are comparable to
      ours. As far as prognostic factors are concerned, this report provides evidence
      that the explainable variables which influence survival depend on the tumor and
      patient status.

PMID- 9755749
TI  - [Retrospective analysis of the reproducibility of the daily set-up of the
      irradiation fields of cancer of the rectum using a megavoltage imaging system].
AB  - PURPOSE: To evaluate a ionization chamber on-line portal imaging system in
      routine clinical radiotherapy of rectum cancers. PATIENTS AND METHODS: Megavolt
      portal images were obtained using a fast electronic megavoltage radiotherapy
      imaging system in 13 cases of pelvic fields. A total of 208 portal images and 13
      simulator films were used to determine the values of set-up deviations in the X-Z
      directions of a fixed co-ordinate system, and of the rotation fields (R).
      RESULTS: Mean standard deviations of the difference between simulation and
      treatment images were 3.2 mm and 0.9 mm for X and Z, 3.6 mm for the rotation
      fault. The standard deviations were, respectively, 7.1 mm, 7.1 mm and 1.5 mm. The
      cumulative frequency distributions revealed that 80% and 95% of the absolute
      differences were less than 10 mm and 17.5 mm, respectively. CONCLUSION: These
      results indicate the difficulty of a reproducible daily set-up. A weekly control
      could be proposed in order to increase the quality of pelvic site treatment. The
      introduction of masks to improve the set-up is also discussed.

PMID- 9755748
TI  - Radical radiotherapy of localised prostate cancer: the relationship between
      radiation dose and survival.
AB  - PURPOSE: This retrospective study aims to define the effects of different
      radiation dose levels on survival, local control and toxicity in a series of 208
      patients with localised prostate cancer consecutively treated with radical
      radiation therapy. PATIENTS AND METHODS: From 1982 through 1996, 365 patients
      with prostate cancer have been consecutively treated with radical radiotherapy in
      Florence (n = 306) and Arezzo (n = 59). The 208 cases treated until January 1994
      with Stage B (125/208, 60%) and C (83/208, 40%) are the objects of the present
      study. The treatment was most often limited to the prostatic area (81%), using a
      four-field "box technique" and 25 MV photon beams, up to a total dose of 60-65 Gy
      (21% of the patients), of 66-69 Gy (26%) and of 70 Gy (53%); conventional
      fractionation was used (fractional dose: 2 Gy; five fractions/week). Hormonal
      therapy was also given to 39% of the cases. The possible relationship between
      dose, stage, grading and survival has been analysed. The survival figures and the
      types of relapse observed (prostatic, lymphnodal or "biochemical") have been
      analysed also according to the extent of the target volume and to the prostate
      specific antigen (PSA) value at diagnosis, in the entire series or in selected
      subgroups. RESULTS: In the whole series and also after radiation alone, the
      patients with Stage B, with more differentiated tumours and those treated with
      higher doses to the prostate obtained significantly better survival results.
      Multivariate analysis confirmed that the dose level has an independent prognostic
      value. The use of a limited target volume did not produce an excess of pelvic
      lymphnodal failures. Among the patients more recently treated with radiation
      alone, the PSA level at diagnosis is strongly related with the risk of local and
      "biochemical" failure, and also with the relapse-free survival. Toxicity was
      acceptable, also for the patients treated with higher doses, but late treatment
      related damage is more frequent in patients treated on larger volumes.
      CONCLUSION: The results of this retrospective analysis confirm the good results
      of small volume, high dose radiation therapy of prostatic cancer, even taking
      into account the possible biases due to the retrospective nature of the study,
      and the relevance of the PSA level at diagnosis to define the risk of local
      failure.

PMID- 9755750
TI  - [Tolerance and role of irradiation in the treatment of epithelial cancer of the
      ovary].
AB  - PURPOSE: In a retrospective analysis, our aim was to evaluate the immediate
      tolerance and the early and late complications of abdomino-pelvic radiotherapy in
      the Centre Alexis-Vautrin (France). PATIENTS AND METHODS: From 1st January 1983
      to 31st December 1993, 117 patients were treated at Centre Alexis Vautrin in
      Nancy for epithelial ovarian cancer by abdominal and/or pelvic irradiation after
      surgery. They were aged from 24 to 85 with a median of 56 years. There were ten
      patients with stage I (9%), 28 patients with stage II (24%), 60 patients with
      stage III (61%) and 19 patients with stage IV (16%) disease. Results of surgery
      were determined as follows: satisfactory with absence of tumoral residuum in 26%
      cases (30 patients) and with residuum inferior to 20 mm in 46% cases (52
      patients; incomplete in 26% cases (31 patients) either because of residuum
      superior in 20 mm and/or incomplete surgery; and not evaluable in 3% cases (four
      patients). Seventy-seven patients were sent to the Centre for postoperative
      treatment (66% patients of the series), 48 of them (62.4%) after non-satisfactory
      surgery, 29 after satisfactory surgery (37.6%). Chemotherapy was administered to
      only 104 patients (89% cases), and contained platinum salts and cyclophosphamid
      for 87% of these patients. Fourteen patients (12%) received a single irradiation
      dose after surgery: three in stage I, three with poor evaluation of the disease
      in the initial stage, three with medical contraindications to chemotherapy
      treatment, six with contraindications due to advanced age (?? Makes 15 ).
      Histologically, 46% of patients had a serous adenocarcinoma, 9% a mucinous
      adenocarcinoma, 11% an endometrioid adenocarcinoma, 2% a clear cell
      adenocarcinoma, 1% an undifferentiated adenocarcinoma, and 31% an epithelial
      carcinoma without any other indication. The histological grade which was recently
      introduced was rarely indicated. Complementary radiotherapeutic treatment
      consisted of pelvic irradiation for 14 patients (12%), abdomino-pelvic
      irradiation for 63 patients (54%), and total abdominal irradiation with a pelvic
      boost for 40 patients (34%). RESULTS: The immediate tolerance to irradiation can
      be considered as globally satisfactory since 9% of the patients (ten cases) had
      no problems and 64% of the patients developed a minor intolerance easily
      controlled by symptomatic treatments. There were also digestive complications:
      nausea, vomiting and diarrhea for 66% of the patients (50 cases); to a lesser
      extent, 20% of the cases experienced associated digestive and hematological
      complications (15 patients); 9% isolated hematological troubles such as anemia
      (seven patients); 4% digestive complications (three patients) and 1%
      hematological and urinary digestive troubles (one patients). Late irradiation
      sequelae were evaluated for 89 patients with a follow-up lasting from 4 months to
      11 years. Sixty-six patients had no sequelae, eleven patients had minor
      tolerability problems--mainly digestive for more than half of them. Five patients
      presented severe complications, including hematological problems such as chronic
      thrombopenia in two cases, urinary-problems in two other cases, and one patient
      presented with a case of histologically proven malabsorption. Two patients
      presented major problems; one case of radic cystitis and one of radic bowel. Two
      patients died of iatrogenic causes: one of induced leukemia, the other of
      treatment-induced digestive and renal complications. The overall survival rate
      was 30% at 5 years and 22% at 10 years. It was 90% at 5 and 10 years for stage I
      patients, 60% at 5 years and 30% at 10 years for stage II patients, 22% at 5
      years and 8% at 10 years for stage III patients, and finally 10% at 5 years for
      stage IV patients. CONCLUSION: In this retrospective analysis of 117 epithelial
      ovarian cancers, treated over 10 years and which all received pelvic and/or
      abdominal irradiation, we can conclude that this treatment is globally well
      tolerated and that it yields a

PMID- 9755751
TI  - [Radiosurgery of single brain metastasis without combined total cerebral
      irradiation. Results of a consecutive series of 12 cases].
AB  - PURPOSE: To evaluate the usefulness of radiosurgery without whole brain
      irradiation for a solitary brain metastasis. PATIENTS AND METHODS: Between
      December 1994 and November 1996, 12 patients were treated for a single brain
      metastasis by radiosurgery alone. Median age was 53, and 10 patients had a
      Karnofsky performance status above 70. Half the patients had active extracranial
      disease at the time of radiosurgery. Stereotactic radiosurgery delivered a single
      dose of 20 Gy (specified at the isocenter with a 70% isodose reference curve).
      Evaluation of results was performed according to local control, survival,
      evolution of performance status, as well as evolution of neurologic symptoms.
      RESULTS: No patient had immediate toxicity. One month later, ten patients showed
      improvement in their neurologic impairments, and none had progression of the
      cerebral lesion according to CT scan evaluation (diminution for seven patients,
      and stabilization for five). Local control rate was 58%, and median time to
      failure was 4 months. The overall median survival time was 10 months. Three
      patients were alive, with good performance status, and six died following
      cerebral progression. CONCLUSION: These poor results in terms of local control
      are in favor of supplementary whole brain irradiation, except for particular
      cases.

PMID- 9755752
TI  - [Radiation-induced sarcoma after breast cancer. Apropos of 8 cases and review of
      the literature].
AB  - PURPOSE: Retrospective analysis of eight new cases of radiation-induced sarcomas
      following radiotherapy for breast carcinoma and literature review. PATIENTS AND
      METHODS: Eleven patients presenting with radiation-induced sarcoma after
      radiotherapy for breast cancer have been treated between 1983 and 1997 at Henri
      Mondor University Hospital (France). Eight of these patients respected the
      criteria established by Cahan et al. The others had Stewart-Treves Syndrome and
      were thus excluded from the analysis. Only one of the eight patients had received
      chemotherapy. All of the patients at the time of diagnosis of radiation-induced
      sarcoma were free of breast cancer recurrence. Radiation-induced sarcoma appeared
      with a latency period of 5 to 18 years (mean: 10.3 years). Patients' ages ranged
      from 39 to 88 years (mean: 57.6 years) at the time of diagnosis of sarcoma. Three
      sarcomas occurred in the treated breast, two in the chest wall, one in the
      preclavicular area and two in the axillary region. There were two angiosarcomas,
      three fibrosarcomas, one osteosarcoma, one malignant fibrous histiocytoma (MFH),
      and one undifferentiated sarcoma. All patients have received treatment for their
      sarcoma: all of them underwent surgery, one patient combined radiotherapy and
      chemotherapy, and three patients chemotherapy. RESULTS: Two patients were alive
      and free from disease. Six patients died (5-34 months); all six had local and/or
      metastatic recurrence. CONCLUSIONS: Radiotherapy can induce malignancies after a
      latent period of several years. Radiation-induced sarcomas are associated with
      poor overall prognosis. The treatment in most of the cases is late and
      ineffective, therefore careful follow-up is needed. There are still many
      uncertainties and questions about radiation-induced sarcomas.

PMID- 9755753
TI  - [Chondrosarcoma in Ollier's disease. Apropos of 2 cases and review of the
      literature].
AB  - Ollier's disease is a rate affliction (not more than approximately 100 cases have
      been reported over a 30-year period) characterized by bone dysplasia in which
      evolution to degenerative neoplasia has been described. Diagnosis of
      chondrosarcoma is delicate in these cases. It is a kind of slowly evolving low
      grade malignant tumor. Surgery is the primary treatment course, and can lead to
      remission. Prognosis, depending on the number and dimension of the lesions, their
      localization and metastasis prevention, is usually good, but relapses are
      relatively frequent: 25 to 50%. In case of relapse, radiotherapy and chemotherapy
      were tested but their efficacy is limited. We report here two clinical cases and
      discuss literature data.

PMID- 9755754
TI  - [Use of a multileaf collimator for the production of intensity-modulated beams].
AB  - In external radiotherapy, the use of intensity modulated fields has been proposed
      for tissue and non-homogeneity compensation or for the generation of conformal
      dose distributions. Multileaf collimators can be employed dynamically for the
      modulation of the X-ray field in two dimensions. Efficient dynamic collimation
      became possible due to advances in computer and linear accelerator technology. It
      presents a number of advantages over conventional methods such as the use of
      compensators. We have developed a program which calculates, from a given
      intensity distribution, the motion of the MLC leaves as a function of monitor
      units, and we have applied it on a Varian linear accelerator with a 40 pair
      multileaf collimator. The analysis of the experimental results demonstrates the
      feasibility and the potential of the method.

PMID- 9755756
TI  - [Activity of stereotactic radiosurgery and radiotherapy in France. SFRO-1997
      survey].

PMID- 9755757
TI  - What is computer assisted orthopaedic surgery?

PMID- 9755755
TI  - [Cutaneous lymphoma in Tunisia: clinical profile and therapeutic results].
AB  - PURPOSE: The aim of this retrospective study was to investigate therapeutic
      result of cutaneous lymphoma in Tunisia. PATIENTS AND METHODS: Between January
      1969 and June 1994, 100 patients with cutaneous lymphoma were referred either to
      Salah Azaiz Institute or the other University Hospitals of Tunisia. Fifty-one
      patients had epidermotropic lymphoma and 49 non-epidermotropic lesions. Eighty
      seven patients received complete treatment. Puvatherapy and other local
      dermatologic treatments were used for early stage mycosis fungoides. Thirty-two
      patients benefited from radiotherapy, with curative dose in 28 cases.
      Chemotherapy including anthracyclin agents was used for high grade lymphoma.
      Thirteen patients had association of radiotherapy and chemotherapy. RESULTS: Five
      year survival rates were 50% for patients with epidermotropic lesions and 56% for
      patients with non-epidermotropic cutaneous lymphoma. Statistical study has not
      identified any significant prognosis factor. CONCLUSION: Radiotherapy and
      chemotherapy are both effective. Treatment should depend on stage and histologic
      type.

PMID- 9755758
TI  - Computer-integrated surgery. Technology and clinical applications. 1996.

PMID- 9755759
TI  - Computer assisted orthopaedic surgery. Image guided and robotic assistive
      technologies.
AB  - Technologies are emerging that will influence the way in which orthopaedic
      surgery is planned, simulated, and performed. Recent advances in the fields of
      medical imaging, computer vision, and robotics have provided the enabling
      technologies to permit computer aided surgery to become an established area which
      can address clinical needs. Although these technologies have been applied in
      industry for more than 20 years, the field of computer assisted orthopaedic
      surgery is still in its infancy. Image guided and surgical navigation systems,
      robotic assistive devices, and surgical simulators have begun to emerge from the
      laboratory and hold the potential to improve current surgical practice and
      patients' outcomes. The goals of these new clinically focused technologies are to
      develop interactive, patient specific preoperative planners to optimize the
      performance of surgery and the postoperative biologic response, and develop more
      precise and less invasive interactive smart tools and sensors to assist in the
      accurate and precise performance of surgery. The medical community is beginning
      to see the benefit of these enabling technologies which can be realized only
      through the collaboration and combined expertise of engineers, roboticists,
      computer scientists, and surgeons.

PMID- 9755760
TI  - Medical imaging and registration in computer assisted surgery.
AB  - Imaging, sensing, and computing technologies that are being introduced to aid in
      the planning and execution of surgical procedures are providing orthopaedic
      surgeons with a powerful new set of tools for improving clinical accuracy,
      reliability, and patient outcomes while reducing costs and operating times.
      Current computer assisted surgery systems typically include a measurement process
      for collecting patient specific medical data, a decision making process for
      generating a surgical plan, a registration process for aligning the surgical plan
      to the patient, and an action process for accurately achieving the goals
      specified in the plan. Some of the key concepts in computer assisted surgery
      applied to orthopaedics with a focus on the basic framework and underlying
      technologies is outlined. In addition, technical challenges and future trends in
      the field are discussed.

PMID- 9755761
TI  - Computer assisted orthopaedic surgery with image based individual templates.
AB  - Recent developments in computer assisted surgery offer promising solutions for
      the translation of the high accuracy of the preoperative imaging and planning
      into precise intraoperative surgery. Broad clinical application is hindered by
      high costs, additional time during intervention, problems of intraoperative man
      and machine interaction, and the spatially constrained arrangement of additional
      equipment within the operating theater. An alternative technique for computerized
      tomographic image based preoperative three-dimensional planning and precise
      surgery on bone structures using individual templates has been developed. For the
      preoperative customization of these mechanical tool guides, a desktop computer
      controlled milling device is used as a three-dimensional printer to mold the
      shape of small reference areas of the bone surface automatically into the body of
      the template. Thus, the planned position and orientation of the tool guide in
      spatial relation to bone is stored in a structural way and can be reproduced
      intraoperatively by adjusting the position of the customized contact faces of the
      template until the location of exact fit to the bone is found. No additional
      computerized equipment or time is needed during surgery. The feasibility of this
      approach has been shown in spine, hip, and knee surgery, and it has been applied
      clinically for pelvic repositioning osteotomies in acetabular dysplasia therapy.

PMID- 9755762
TI  - Pedicle screw placement using image guided techniques.
AB  - Clinical evaluation of a computer assisted spine surgical system is presented.
      Eighty pedicle screws were inserted using computer assisted technology in
      thoracic and lumbar vertebrae for treatment of different types of disorders
      including fractures, spondylolisthesis, and scoliosis. Fifty-two patients with
      severe fractures, spondylolisthesis, or pseudoarthrosis of T10 to L5 were treated
      using a computer assisted technique on 1/2 the patients and performing the screw
      insertion manually for the other 1/2. At the same time, 28 pedicle screws were
      inserted in T12 to L4 vertebrae for scoliosis with the help of the computer
      assisted technique. Surgery was followed in all cases (66 vertebrae; 132 pedicle
      screws) by postoperative radiographs and computed tomographic examination, on
      which measurements of screw position relative to pedicle position could be done.
      For fractures, spondylolisthesis, or pseudarthrosis, comparison between the two
      groups showed that four screws in 52 (8%) vertebrae had incorrect placement with
      computer assisted technique whereas 22 screws in 52 (42%) vertebrae had incorrect
      placement with manual insertion. In patients with scoliosis, four screws in 28
      (14%) vertebrae had incorrect placement. In all of the patients (132 pedicle
      screws) there were no neurologic complications. These results show that a
      computer assisted technique is much more accurate and safe than manual insertion.

PMID- 9755763
TI  - Computer assisted knee replacement.
AB  - Accurate alignment of knee implants is essential for the success of total knee
      replacement. Although mechanical alignment guides have been designed to improve
      alignment accuracy, there are several fundamental limitations of this technology
      that will inhibit additional improvements. Various computer assisted techniques
      have been developed to examine the potential to install knee implants more
      accurately and consistently than can be done with mechanical guides. For example,
      computer integrated instrumentation incorporates highly accurate measurement
      devices to locate joint centers, track surgical tools, and align prosthetic
      components. Image guided knee replacement provides a three-dimensional
      preoperative plan that guides the placement of the cutting blocks and prosthetic
      components. Robot assisted knee replacement allows one to machine bones
      accurately without the use of standard cutting blocks. The rationale for the
      development of computer assisted knee replacement systems is presented, the
      operation of several different systems is described, the advantages and
      disadvantages of different approaches are discussed, and areas for future
      research are suggested.

PMID- 9755764
TI  - Computer assisted reconstruction of the anterior cruciate ligament.
AB  - Reconstruction of the anterior cruciate ligament is a delicate task for which
      many different techniques have been proposed. A system consisting of a computer
      and a three-dimensional optical sensor is proposed to help the surgeon control
      the placement of a graft. This system can be used to minimize anisometry of the
      graft and avoid notch impingement. The same system, which had been validated by
      previous testing on 20 fresh human anatomic specimen knees, was tested on 23
      patients who had an anterior cruciate ligament injury. Tunnel placement was
      performed using the standard technique of Morgan et al and was measured with the
      computer based system. It was found that all cases had different configurations
      of tibial and femoral placement. The computer based anisometry measurements
      ranged from 1.9 mm to 8.8 mm in the anterior part of the graft, and from 1 mm to
      13 mm in the centers of the tunnels. Using the computer retrospectively, it was
      possible to find configurations of the graft in all cases that avoid notch
      impingement, with anisometry values ranging from 1.3 mm to 3.7 mm. This study
      shows that a computer based system can be a useful tool for routine anterior
      cruciate ligament reconstruction and can be useful for research purposes.

PMID- 9755765
TI  - Computer assistance in arthroscopic anterior cruciate ligament reconstruction.
AB  - Accurate placement of the graft is considered one of the most important factors
      in anterior cruciate ligament surgery. However, reconstruction with contemporary
      guiding systems still can result in unacceptable graft placement variability. To
      improve the reproducibility of graft placement, intraoperative visual feedback
      was added to the arthroscopic technique. First, fluoroscopic visualization was
      added to evaluate guidewire placement before tunnel drilling. Second, computer
      graphic overlays were added to the fluoroscopic view. Three groups of patients
      were treated: 29 patients with arthroscopy, 53 patients with fluoroscopy added,
      and 50 patients with computer overlays added. Graft placement variability was
      reduced significantly with fluoroscopic visualization. Computer overlays resulted
      in additional significant reductions in graft placement variability. Simple
      visual enhancements seem to be useful in improving the accuracy of arthroscopic
      anterior cruciate ligament reconstruction.

PMID- 9755766
TI  - Computer assisted measurement of cup placement in total hip replacement.
AB  - The introduction of image guided systems in total hip replacement surgery
      provides the ability to plan precisely the alignment of the acetabular cup before
      surgery, and to perform the surgery according to the preoperative plan.
      Preoperative planners (interactive computer programs for surgical planning) based
      on three-dimensional medical images allow planning of optimal placement of
      implant components based on simulated implant performance. Exact measurement of
      the cup position during surgery allows precise placement of the cup and accurate
      measurement of the final position of the cup relative to the pelvis. This
      measurement is used to evaluate the radiographic techniques for postoperative
      measurement of cup alignment. Malposition of the acetabular component increases
      the occurrence of impingement, reduces the safe range of motion, and increases
      the risk of dislocation and wear. Dislocation of the implant after total hip
      replacement remains a significant clinical problem. Not fully understanding the
      interaction between pelvic orientation and final acetabular cup alignment may be
      one of the main contributing factors in the continued significant incidence of
      dislocations after total hip replacement. In this study an attempt was made to
      link the preoperative planning, intraoperative placement, and postoperative
      measurement of cup placement in total hip replacement using computer assisted
      techniques.

PMID- 9755767
TI  - Primary and revision total hip replacement using the Robodoc system.
AB  - The ROBODOC system was designed to address potential human errors in performing
      cementless total hip replacement. The system consists of a preoperative planning
      computer workstation (called ORTHODOC) and a five-axis robotic arm with a high
      speed milling device as an end effector. The combined experience of the United
      States Food and Drug Administration multicenter trial and the German postmarket
      use of the system are reported. The United States study is controlled and
      randomized with 136 hip replacements performed at three centers (65 ROBODOC and
      62 control). Followup was 1 year on 127 hip replacements and 2 years on 93 hip
      replacements. No differences were found in the Harris hip scores or the Short
      Form Health Survey outcomes questionnaire. Length of stay also was not different,
      but the surgical time and blood loss were greater in the ROBODOC group. This was
      attributed to a learning curve at each center. Radiographs were evaluated by an
      independent bone radiologist and showed statistically better fit and positioning
      of the femoral component in the ROBODOC group. Complications were not different,
      except for three cases of intraoperative femoral fracture in the control group
      and none in the ROBODOC group. The German study reports on 858 patients, 42 with
      bilateral hip replacements and this includes 30 revision cases for a total of 900
      hip replacements. The Harris hip score rose from 43.7 to 91.5. In these cases the
      surgical time declined quickly from 240 minutes for the first case to 90 minutes.
      No intraoperative femoral fractures occurred in 900 cases. Other complications
      were comparable with total hip replacements performed using conventional
      techniques. The ROBODOC system is thought to be safe and effective in producing
      radiographically superior implant fit and positioning while eliminating femoral
      fractures.

PMID- 9755768
TI  - Computer assistance for pelvic osteotomies.
AB  - To assist surgeons performing pelvic osteotomies for the treatment of dysplastic
      hips, an image guided freehand navigation system has been developed. Preoperative
      computed tomographic scan images are presented in various ways to the surgeon
      together with real time display of the instruments and surgical action on the
      computer screen. The system supports the preoperative plan and provides optimized
      control of surgical action. The main focus of the image guidance has been placed
      on the execution of the different required cuts and the reorientation of the
      acetabular fragment. Special attention also has been given to the development of
      a sophisticated surgeon-machine interface. Fourteen surgeries have been performed
      with image guidance so far. The visualization aids provided by the system are
      able to help reduce potential risk and thus increase safety and accuracy for this
      difficult class of surgical interventions.

PMID- 9755769
TI  - Percutaneous iliosacral screw placement using image guided techniques.
AB  - A computer assisted technique of iliosacral screw placement that is applicable to
      unstable pelvic ring fractures is proposed. The goals are to operate
      noninvasively with a percutaneous procedure to decrease the complications of
      surgical exposure and to provide greater accuracy in locating the close
      neurovascular structures. Preoperative computed tomographic images of the pelvis
      are provided and a computed tomography three-dimensional model is built. In this
      model, the optimal trajectories for the drilling are planned. An ultrasound based
      registration is performed intraoperatively. This registration is the most
      original part of this work. After performing the passive drilling guidance step,
      the surgeon places the screws. The accuracy of the ultrasound based registration
      is checked by comparison with a standard surface based registration at the end of
      the test experiment. Each screw position is verified by a computed tomographic
      examination. Four human anatomic specimen pelves were tested with three screw
      insertions for each pelvis (12 screws). All of the screws were considered to be
      placed correctly. The method is safe and encourages the start of clinical
      application.

PMID- 9755770
TI  - Augmented reality and its future in orthopaedics.
AB  - Augmented reality is a display technique that combines supplemental information
      with the real world environment. Augmented reality systems are on the verge of
      being used everyday in medical training, preoperative planning, preoperative and
      intraoperative data visualization, and intraoperative tool guidance. The basic
      technologies of augmented reality are discussed, augmented reality systems
      currently being used in the medical domain are examined, and some future uses of
      these systems in orthopaedic applications are explored.

PMID- 9755771
TI  - Electromyographic analysis of shoulder joint function of the biceps brachii
      muscle during isometric contraction.
AB  - Surface electromyography was performed for both heads of the biceps brachii in 11
      healthy men while the muscles were under 30% maximum isometric shoulder flexion
      and abduction. Elbow related biceps activity was minimized by using a brace
      locked in neutral forearm rotation. Electromyographic activity was normalized as
      a percentage of maximal muscle contraction during 24 shoulder motions.
      Electromyographic activity was detected in all motions examined, suggesting that
      the biceps muscle acts as a flexor and an abductor of the shoulder. Both heads of
      the biceps muscle had higher activities during external rotation than during
      internal rotation for most motions. Activities of both heads increased with arm
      elevation, but showed little dependence on elbow position. The long head was
      still active during internal rotation of the shoulder. These findings also
      suggest that the biceps muscle is a flexor and an abductor of the shoulder, and
      that the long head can act as a humeral head stabilizer in superior and anterior
      directions. Muscle fatigue of the biceps and the deltoid muscle also was
      determined at 30% of maximum isometric flexion. All muscles had significantly
      decreased mean power frequency and turns count, and increased amplitude and
      integrated electromyography. The rate of decrease in mean power frequency was
      larger for the biceps than for the deltoid muscle, and the rate of increase in
      amplitude was larger for the long head of the biceps than for the short head or
      for the deltoid muscle. These findings suggest that the long head of the biceps
      must increase its mechanical output to keep the arm in elevation to a greater
      extent than do the short head and the deltoid muscle. This may be one of the
      causes of tendinitis or rupture of the long head.

PMID- 9755772
TI  - Shoulder joint kinetics during the push phase of wheelchair propulsion.
AB  - The purpose of this investigation was to quantify the forces and moments at the
      shoulder joint during free, level wheelchair propulsion and to document changes
      imposed by increased speed, inclined terrain, and 15 minutes of continuous
      propulsion. Data were collected using a six-camera VICON motion analysis system,
      a strain gauge instrumented wheel, and a wheelchair ergometer. Seventeen men with
      low level paraplegia participated in this study. Shoulder joint forces and
      moments were calculated using a three-dimensional model applying the inverse
      dynamics approach. During free propulsion, peak shoulder joint forces were in the
      posterior (46 N) and superior directions (14 N), producing a peak resultant force
      of 51 N at an angle of 185 degrees (180 degrees = posterior). Peak shoulder joint
      moments were greatest in extension (14 Newton-meters [Nm]), followed by abduction
      (10 Nm), and internal rotation (6 Nm). With fast and inclined propulsion, peak
      vertical force increased by greater than 360%, and the increase in posterior
      force and shoulder moments ranged from 107% to 167%. At the end of 15 minutes of
      continuous free propulsion, there were no significant changes compared with short
      duration free propulsion. The increased joint loads documented during fast and
      inclined propulsion could lead to compression of subacromial structures against
      the overlying acromion.

PMID- 9755773
TI  - The triceps preserving approach to total elbow arthroplasty.
AB  - Elbow arthroplasty most commonly is performed through a posterior approach by
      detaching or reflecting the triceps off the olecranon. Surgical approaches to the
      elbow joint that dissociate the triceps from the olecranon have distinct
      disadvantages. Triceps avulsion, triceps weakness, and wound healing problems
      have been reported. Such complications necessitate more surgery and predispose
      the joint to an infection. To avoid these complications a modified posterior
      approach to the elbow joint that preserves the triceps muscle insertion on the
      olecranon was used in 10 consecutive elbow arthroplasties. This method provides
      adequate exposure, allows early rehabilitation, and avoids triceps weakness.

PMID- 9755774
TI  - Right versus left symmetry of ulnar variance. A radiographic assessment.
AB  - One hundred skeletally mature healthy volunteers underwent standardized bilateral
      posteroanterior radiographs in unloaded (static) and loaded (dynamic) conditions
      to determine the symmetry of ulnar variance. The mean age was 32 +/- 9 years
      (range, 19-61 years), with 58 women and 42 men. Ulnar variance was measured to
      the closest 0.5 mm using the method of perpendiculars. Three separate
      measurements were made of each radiograph in a blinded fashion by the same
      investigator. An intraobserver standard deviation of 0.21 was used to calculate a
      95% tolerance interval of 0.7 mm (rounded up to 1 mm) as a measure of
      significance. The average static ulnar variance was -0.13 +/- 1.5 mm on the left
      and -0.29 +/- 1.6 mm on the right. The average dynamic ulnar variance was 0.93 +/
      1.5 mm on the left and 0.82 +/- 1.5 mm on the right. When compared individually,
      there was a greater than or equal to 1 mm side to side difference in 37% of
      volunteers under static and 38% under dynamic conditions. There were no
      significant correlations between ulnar variance measurements and patient age,
      gender, race, or handedness. Use of the normal wrist radiograph as a baseline for
      static radial length measurements is valid in only 63% of cases.

PMID- 9755775
TI  - Radiographic predictors of outcome of core decompression for hips with
      osteonecrosis stage III.
AB  - Various investigators have studied the prognostic influence of various
      demographic, laboratory, and radiographic parameters on outcome for different
      treatment methods for osteonecrosis of the femoral head. A cross sectional study
      was done of 52 patients (68 hips) who had a core decompression for Ficat and
      Arlet Stage III osteonecrosis of the femoral head. The purpose of this study was
      to evaluate the prognostic significance of various radiographic factors for risk
      of disease progression after treatment with core decompression. Radiographic
      parameters included Steinberg stages (III or IV), Ohzono stage (central or
      lateral location), amount of head depression, extent of crescent sign arc, and
      extent of lesion by Kerboul combined necrotic angle measurements. Patient outcome
      assessment was at a followup mean of 12 years (range, 4-18 years) after core
      decompression. Overall, 20 of the 68 hips (29%) had satisfactory outcomes. Of the
      44 hips with Steinberg Stage III disease, 18 (41%) underwent total hip
      arthroplasty. In comparison, in the Steinberg Stage IV hips, 22 of 24 hips (92%)
      underwent arthroplasty. Ohzono Stage B lesions had 50% survival (eight of 16
      hips) compared with 23% survival (12 of 52 hips) for Ohzono Stage C. Hips with
      combined necrotic angles greater than 250 degrees had 16% survival (seven of 45)
      which can be compared with 57% survival (13 of 23) for hips with angles less than
      250 degrees. The best multiple regression model for a satisfactory outcome was a
      Steinberg Stage III hip (no head depression), a central lesion (Ohzono Stage B),
      and a small lesion (< 250 degrees combined necrotic angle). With this
      combination, there were 89% satisfactory outcomes (8 of 9 hips). Conversely, the
      best generalized linear model for unsatisfactory outcomes (0 hips surviving of
      14) was Steinberg Stage IV disease (head depression), lateral location (Ohzono
      Stage C lesion), and a large extent of the lesion (> 250 degrees combined
      necrotic angle).

PMID- 9755776
TI  - Patella height after high tibial osteotomy with internal fixation and early
      motion.
AB  - The purpose of this study was to compare the incidence of patella infera in
      patients after high tibial osteotomy treated with either postoperative
      immobilization or internal fixation and early range of motion. A retrospective
      review of 98 patients with high tibial osteotomy was done at the authors'
      institution. Thirty-three patients who had secondary procedures such as
      concomitant ligamentous reconstruction with early motion were excluded.
      Therefore, 69 knees in 65 patients remained in the study cohort. Group A
      consisted of 32 patients (34 knees) treated with postoperative immobilization,
      whereas Group B included 33 patients (35 knees) treated with internal fixation
      and early motion. The preoperative and postoperative Insall-Salvati index,
      Blackburne-Peel index, and angular alignment were determined for each group.
      Between Groups A and B, the differences in the Insall-Salvati index and the
      Blackburne-Peel index were statistically significant, although the difference in
      angular correction was not significant. With rigid fixation and early motion the
      Insall-Salvati index showed that there was less postoperative shortening of the
      patellar tendon. The relationship of the patella to the remainder of the knee was
      affected less adversely as evidenced by the Blackburne-Peel index. High tibial
      osteotomy with internal fixation and early range of motion should result in a
      better knee and ease the subsequent performance of a total knee arthroplasty.

PMID- 9755777
TI  - Pseudoaneurysm after high tibial osteotomy and limb lengthening.
AB  - A case of a young man with anterior tibial artery rupture and pseudoaneurysm
      formation that occurred during lengthening of a scarred limb is presented. Leg
      length discrepancy occurred because of previous distal femoral and proximal
      tibial fractures. Two corrective operations were performed 11 and 2 years earlier
      at another hospital. As limb deformity persisted, distal femoral and proximal
      tibial osteotomies combined with limb lengthening were performed. The aim was to
      achieve 120 mm (70 mm femoral, 50 mm tibial) lengthening. The operative and early
      postoperative course was uneventful. Twenty-six days after surgery (when femoral
      and tibial lengthening was 13.5 mm and 5.5 mm, respectively), blood began oozing
      from the operative scar during limb distraction. At 70 days after surgery (when
      femoral and tibia lengthening was 41.5 mm and 14 mm, respectively), a rupture and
      pseudoaneurysm of the anterior tibial artery became apparent. Documentation of a
      normal pulses in the foot after surgery, the late presentation of pseudoaneurysm,
      and the initiation of bleeding by limb distraction indicate that limb lengthening
      either aggravated an unrecognized arterial injury or precipitated de novo rupture
      of the anterior tibial artery scarred from previous trauma. The pseudoaneurysm
      was treated successfully by transarterial embolization.

PMID- 9755778
TI  - Relationship between gait and clinical results after high tibial osteotomy.
AB  - Thirty-two patients with primary osteoarthritis of the medial compartment of the
      knee were studied prospectively to assess the relationship between clinical
      results, limb alignment, and adduction moment of the knee. Clinical and
      radiographic examination and gait analyses were performed preoperatively and
      repeated at 6 months and at 1, 3, and 6 years after high tibial osteotomy. The
      preoperative peak adduction moment was high in 25 patients and low in seven. In
      both groups, the adduction moment of the knee decreased at 6 months after surgery
      but increased after that period. Alignment of the affected knee in both groups
      remained valgus after surgery (average femorotibial angle, 167 degrees-169
      degrees). Clinical outcome in both groups improved after surgery and remained
      unchanged after 1 year. The peak adduction moment of the knee for the whole group
      significantly correlated with alignment and foot angle before and 6 years after
      surgery but did not correlate with stride length and walking velocity. In
      addition, only alignment was associated significantly with clinical results at 6
      years. These results suggest that the preoperative peak adduction moment of the
      knee does not correlate with clinical or radiographic outcomes of high tibial
      osteotomy, provided sufficient valgus alignment is achieved at surgery.

PMID- 9755779
TI  - Postlaminectomy and postirradiation kyphosis in children and adolescents.
AB  - This is a retrospective review of 12 patients treated for severe postlaminectomy
      and postirradiation kyphosis by one surgeon from 1977 to 1994. The average age of
      the patients was 15 years with a range from 2 to 35 years. The duration of
      followup ranged from 24 months to 156 months with an average of 65 months. All
      patients had undergone multilevel laminectomies or irradiation of the thoracic or
      lumbar spine for an intraspinal lesion or trauma. The average preoperative
      kyphosis was 84 degrees and this was reduced to an average of 39 degrees after
      surgery. There were no pseudarthroses and there was an average loss of correction
      of 5 degrees. There were no complaints of back pain. Moderately severe but
      flexible kyphoses were treated in three patients by posterior instrumentation and
      spinal fusion. The other nine patients had combined anterior release or
      decompression and fusion combined with posterior instrumentation and spinal
      fusion. Bracing failed to halt the progressive kyphosis in those patients for
      whom it had been attempted. The only major complications in this series were two
      wound infections in patients previously treated with irradiation.

PMID- 9755780
TI  - The evolution of femoral shaft plating technique.
AB  - There has been an evolution in the AO/Association for the Study of Internal
      Fixation plating technique during the past 3 decades that includes the use of
      longer plates and fewer plate screws, fewer lag screws outside the plate, fewer
      unicortical screws at the plate periphery, and greater use of the 95 degrees
      blade plate to achieve balanced fixation of proximal and distal shaft fractures.
      These changes reflect an evolving technique of plate osteosynthesis that
      emphasizes indirect reduction techniques, biologic internal fixation, and
      improved biomechanics. Outcome data suggest that there has been an improvement
      with time that is reflected by shorter time to union, a decrease in the frequency
      of implant failures, delayed unions, nonunions, malunions, number of
      reoperations, and in overall rate of failure. The best predictor of success was
      the length of plate by logistic regression analysis. With the evolution of
      plating techniques and a greater emphasis on biology of fracture healing, the
      incidence of complications and failures has decreased after femoral shaft
      plating. Plate osteosynthesis of the femoral shaft is particularly advantageous
      in many situations and can be quite successful (87% success rate in Group III).

PMID- 9755781
TI  - Effect of methotrexate on distraction osteogenesis.
AB  - To assess the potential of using distraction osteogenesis to reconstruct bone
      deficient limbs after limb salvage for musculoskeletal sarcomas, the authors
      examined the effect of methotrexate on distraction osteogenesis in a rabbit
      tibial lengthening model. Eighteen rabbits underwent tibial corticotomy and
      application of a ring external fixator. Rabbits were assigned randomly to one of
      two groups in which either methotrexate (n = 12) or placebo (n = 6) was
      administered during a 21-day distraction period. Serum methotrexate levels and
      complete blood cell counts were monitored during distraction, and radiographs of
      the tibia were obtained weekly. Half of the animals from each group were
      sacrificed at the end of distraction, and the remaining animals were sacrificed
      after 6 weeks of neutral fixation when bone normally bridges the gap. Using
      methotrexate at serum concentrations similar to those used clinically for the
      treatment of human osteosarcomas, the authors were unable to show significant
      radiographic, histologic, or chemical differences in the effect of this
      antineoplastic drug on distraction osteogenesis in the rabbit model.

PMID- 9755782
TI  - Periosteal augmentation of the acetabulum.
AB  - The periosteum in children and especially infants has significant osteogenic
      potential. To determine the efficacy of periosteal flaps to assist in improving
      acetabular coverage in children with acetabular dysplasia, a series of
      experiments were designed using young rabbits. Three groups of five rabbits each
      had periosteal flaps fashioned and brought down from the anterolateral aspect of
      the innominate bone superior to the acetabulum and sutured to the capsule of the
      hip. The study was designed to examine the effects of the periosteal cambium
      layer in the formation of new bone to augment the acetabulum and to determine the
      effects of a periosteal flap plus cancellous bone graft. A control group of five
      rabbits underwent a sham operation of an open arthrotomy of the hip. Radiographic
      and histologic examination at 12 weeks revealed augmentation of the acetabulum
      with periosteal flaps that resulted in an average improvement of the acetabular
      index of 3.5 degrees and 6.6 degrees, without and with bone graft, respectively.
      New bone formation from the rim of the acetabulum averaged 3.9 mm with periosteal
      flaps alone and 4.6 mm with bone graft added. Periosteal augmentation of the
      acetabulum in conjunction with established procedures for augmenting acetabular
      coverage would appear to be a useful procedure for improving coverage of the
      femoral head in children with acetabular dysplasia.

PMID- 9755783
TI  - Cartilage changes caused by a coronal surface stepoff in a rabbit model.
AB  - Coronal stepoffs of 0.5 mm (equal to the cartilage height) were created on the
      medial femoral condyles of adult, skeletally mature rabbits as a model for
      articular surface incongruity. After 3, 6, 12, and 24 weeks, tissue was analyzed
      histologically using hematoxylin and eosin and Safranin O staining,
      autoradiographs were made of the femoral condyles, and immunohistologic analysis
      was done for 3-B-3(-) and 7-D-4 chondroitin sulfate epitopes. An overlapping flap
      from the high toward the low side and an increase of the cartilage height on the
      low side of the defect were observed as permanent features of adaptation
      throughout the entire followup. Significant degeneration was not seen around the
      lesion or in the tibial cartilage opposing a stepoff defect. Autoradiography
      showed a three-phase response to the lesion: an early increase in radiolabeled
      sulfate (35SO4) uptake, a sharp decline of 35SO4 uptake, and finally a late
      recovery of the autoradiographic signal indicating partial recovery of
      proteoglycan synthetic activity. After an early increase, immunohistologic
      analysis for 3-B-3(-) showed a subsiding tendency by 24 weeks, and the staining
      with 7-D-4 remained elevated uniformly in the vicinity of the lesion. A rabbit
      femoral stepoff defect with an offset of 0.5 mm may remodel and not lead to
      degeneration within the first 6 months after injury in a stable joint.

PMID- 9755784
TI  - Role of medical capsule and transverse metatarsal ligament in hallux valgus
      deformity.
AB  - The role of the medial capsule and transverse metatarsal ligament in hallux
      valgus deformity including stability of the first metatarsophalangeal and
      adjacent joints was investigated in vitro. The three-dimensional positions of the
      proximal phalanx, first metatarsal, and second metatarsal before and after
      sectioning the medial capsule and metatarsal ligament were measured using a
      magnetic tracking system. Valgus deformity of the hallux increased with medial
      capsule sectioning an average of 22.3 degrees +/- 6 degrees. Valgus deformity of
      the hallux increased with medial capsule and metatarsal ligament sectioning an
      average of 27.4 degrees +/- 9.1 degrees. Valgus deformity of the hallux did not
      change significantly after sectioning the metatarsal ligament only. No
      significant changes were found in varus and eversion of the first metatarsal, in
      valgus of the second metatarsal, in the distance between first and second
      metatarsal heads after sectioning the medial capsule, or in the metatarsal
      ligament. This study shows the importance of the medial capsule in hallux valgus
      deformity. The transverse ligament did not contribute substantially to cause the
      deformity.

PMID- 9755785
TI  - Kappa Delta Award. Low back pain and whole body vibration.
AB  - The investigators describe their multifaceted approach to the study of the
      relationship between whole body vibration and low back pain. The epidemiologic
      study was a two center study of drivers and sedentary workers in the United
      States and Sweden. The vibration exposure was measured in the vehicles. It was
      found that the career vibration exposure was related to low back, neck, and
      shoulder pain. However, disability was related to job satisfaction. In vivo
      experiments, using percutaneous pin mounted accelerometers have shown that the
      natural frequency is at 4.5 Hz. The frequency response is affected by posture,
      seating, and seat back inclination. The response appears to be determined largely
      by the rocking of the pelvis. Electromyographic studies have shown that muscle
      fatigue occurs under whole body vibration. After whole body vibration exposure
      the muscle response to a sudden load has greater latency. Vehicle driving may be
      a reason for low back pain or herniated nucleus pulposus. Prolonged seating
      exposure, coupled with the whole body vibration, should be reduced for those
      recovering from these problems. Vibration attenuating seats and correct ergonomic
      layout of the cabs may reduce the risks of recurrence.

PMID- 9755786
TI  - Unusual soft tissue mass in a 43-year-old man.

PMID- 9755787
TI  - Possibility of a late infection of a joint implant because of dental procedures.

PMID- 9755788
TI  - A personal history of stapedectomy.
AB  - Aristotle has said the essential ingredient of tragedy is first hubris. Fame
      leads to the hubris that offends the gods, who send great punishment. This is so
      true in the history of stapedectomy. The three distinct eras of surgery for
      otosclerosis teach us a lot about what happens in science and in life. The first
      stapes era began in Europe, ahead of its time, and in those halcyon days before
      the turn of the century, the Belle Epoch, proceeded, uncorrected to its tragic
      extreme, and then was stopped suddenly, quite rightly, by the establishment. The
      fenestration era proceeded to an extreme, when its technical master Julius
      Lempert would allow no criticism or improvement in "his" one-stage endaural
      technique, however good, nor would he accept the new mobilization and
      stapedectomy operations, and he and it ended badly. The fact that Jenkins and
      Holmgren would make an opening in the lateral semicircular canal and then close
      it in the epitympanum, not open to the ear canal, to expect to improve hearing is
      amazing. Until Sourdille went to Stockholm and saw one closed fenestration
      operation performed by Holmgren and devised his "open to the ear canal
      technique," the closed fenestration operation was not reasonable. Then Sourdille
      came to New York City, and Lempert heard him speak and read and reread his
      publication and greatly improved on his operation. It was Lempert's one-stage
      endaural open operation that gave the fenestration operation the worldwide
      acceptance it gained. The second stapedectomy era began before the fenestration
      era ended with the accidental and originally unrecognized mobilization of the
      stapes by Rosen and my resurrection of stapedectomy. I realized in reading the
      literature of the past that stapedectomy was not necessarily fatal to the ear or
      the patient as was generally believed, and what was needed was to seal the oval
      window with a living elastic membrane and reconstruct the sound-conducting
      mechanism of the middle ear with a biocompatible implant prosthesis to make it
      successful. But for me, in 1955-1956, the "Zeitgeist" was finally right. I
      realized the stapes could be removed and covered the oval window with a vein
      graft, and Harry Treace made me a biocompatible implant prosthesis out of the
      newly discovered Teflon. For a new technology to be accepted, it must be much
      better than what it replaces, and stapedectomy was much better than fenestration.
      In the new microsurgical era of otology that began, improvements in the
      stapedectomy operation came from everywhere and were readily accepted.
      Stapedectomy has now become so successful, like many treatments in medicine, the
      problem has now largely disappeared. If the measles virus is the cause of the
      growth of the otosclerotic focus, as it seems to be, then vaccination against
      measles eventually will eliminate the hearing loss of otosclerosis completely.
      What the history of stapedectomy reveals is the truth of the quotation from
      Ecclesiastes, "There is nothing new under the sun." Progress is only made when
      the Zeitgeist is right, by someone who puts together the truths of the past with
      the new discoveries of the present.

PMID- 9755789
TI  - Lymphocytes: attackers and targets of the same oncogenic viruses, depending on
      their immunogenic strength.

PMID- 9755790
TI  - Possible retroviral etiology of human breast cancer.
AB  - Since the discovery in the early 1980s that retroviruses are pathogenic to man,
      the mouse mammary tumor viruses (MMTVs) received great attention. Studies of
      MMTVs allowed considerable insights into the mechanisms at work in breast
      tumorigenesis. MMTVs are essentially insertional mutagenes. Numerous oncogenes
      have been found altered by MMTVs, either specific for MMTVs or not. However,
      despite considerable attempts, the involvement of MMTVs in human breast cancer
      remains questionable. Yet a retroviral etiology of human breast cancer cannot be
      discarded since retroviruses are good candidates to play a role in diseases
      which, like human breast cancer, appear either as sporadic or inherited. Due to
      their replication cycle, retroviruses can be propagated not only as infectious
      agents able to freely infect host cells, but also as cellular genes which can be
      passed on to progeny. It is suggested here to search for a new human retrovirus
      in sporadic breast cancer, using the techniques which led to the isolation of
      human T-cell leukemia virus-1 (HTLV-1). Indeed, finding an infectious retrovirus
      in sporadic cases could lead, via the c-DNA probes derived from it, to testing
      the hypothesis that the inherited form of human breast cancer may result from the
      action of retroviral genes integrated in the germ line.

PMID- 9755791
TI  - Epstein-Barr virus in the pathogenesis of Hodgkin's disease.
AB  - Epidemiologic and clinico-pathologic features of Hodgkin's disease suggest that
      an infectious agent may be involved in the pathogenesis of this puzzling
      disorder. Recently accumulated data provide direct evidence supporting a causal
      role of Epstein-Barr virus in a significant proportion of cases. In addition to
      allowing a better understanding of the complex pathogenesis of Hodgkin's disease,
      these virological advances, briefly reviewed herein, also constitute an important
      basis for the development of new therapeutic strategies.

PMID- 9755792
TI  - Human papillomavirus infections in skin cancers.
AB  - Non-melanoma skin cancer (NMSC) is the most frequent cancer among Caucasians
      worldwide. The lesions occur preferentially on sun-exposed sites of the body. The
      role of human papillomavirus (HPV) in the etiology of carcinoma of the genital
      tract is well established. Epidermodysplasia verruciformis (EV) has been regarded
      as a model for NMSC developing on sun-exposed sites. Infection with a specific
      group of HPV types has been associated with the benign and malignant lesions
      occurring in these patients. Recent studies using improved detection methods, as
      well as re-examining material used in previously published studies, reported the
      presence of HPV DNA in NMSC from immunocompetent patients, as well as more than
      90% of NMSC occurring in organ transplant recipients. Five HPV types were
      identified as the most prevalent in these tumors, i.e., HPV 20, HPV 23, HPV 38
      and two newly identified HPV types, DL40 and DL267. These and other HPV types
      were also demonstrated in normal skin biopsies (35%) and a small number of
      melanomas. The frequent presence of more than one HPV type within a lesion was
      noticeable, with at least one type belonging to the EV-associated HPV types.
      Present data indicate that the primary infection with the majority of, if not
      all, HPV types, apparently occurs early in life, after which it remains latent.
      Prolonged ultraviolet (UV) radiation is needed either to activate viral gene
      functions, and/or to inactivate cellular genes responsible for controlled cell
      growth. Further studies are clearly needed to determine the molecular mechanisms
      by which these HPV infections in combination with UV-radiation may contribute to
      this carcinogenic process.

PMID- 9755793
TI  - Hepatitis B viruses and cancerogenesis.
AB  - Hepatitis B virus (HBV) is a small, enveloped DNA virus which primarily infects
      liver cells and causes acute and persistent liver disease. Chronic HBV infection,
      frequently associated with cirrhosis and eventually hepatocellular carcinoma
      (HCC), represents a major health problem in the world. HBV is the prototype
      member of the hepadnavirus family, which includes several related mammalian
      viruses also implicated in liver carcinogenesis in the host. Although
      epidemiological evidence has clearly linked HBV infection with HCC development,
      the precise role of the virus and the molecular mechanisms of liver cell
      transformation remain elusive. Here we discuss potential oncogenic strategies of
      HBV, ranging from indirect mechanisms related to chronic necroinflammatory
      disease and to the effects of viral gene products on cell proliferation and
      apoptosis, to direct insertional activation of cellular (onco)genes. Presently,
      vaccination of high risk populations represents a major way to prevent the
      development of HBV-related liver cancer.

PMID- 9755794
TI  - Latest developments in radiology.

PMID- 9755795
TI  - Contrast agents in magnetic resonance imaging of the liver: present and future.
AB  - New contrast agents are being developed by drug companies to better image the
      liver magnetic resonance imaging (MRI). They can be divided into hepatobiliary
      agents (Gd-EOB-DTPA, Gd-BOPTA, Mangafodipir) and nanoparticulate agents directed
      to the reticulo-endothelial system (ferumoxides, SHU 555A). After intravenous
      injection, all these agents concentrate in the liver and induce profound signal
      changes. Particulate agents induce predominantly a darkening of the liver
      parenchyma, while hepatobiliary agents induce a brightening. In both cases, liver
      lesion conspicuity is enhanced, leading to a better visualization of the lesion.
      After a description of the principal pharmacokinetic characteristics of the
      compounds, this review paper summarizes the utility of the agents in the
      detection and characterization of focal liver diseases.

PMID- 9755797
TI  - Teleradiology.
AB  - According to the American College of Radiology, teleradiology is an electronic
      transmission of radiological images from one location to another for the purposes
      of interpretation or consultation. This article provides a historical perspective
      and discusses both solved and unsolved problems concerning the different elements
      of a teleradiology system (image acquisition, image transmission, image display,
      image compression). It concludes that teleradiology will in the future be a part
      of picture archiving and communication systems (PACS). Technical problems have
      for the most part been solved, with the exception of quality of gray-scale
      monitors. The characteristics of such a system depends on its goals.

PMID- 9755796
TI  - Computed radiography.
AB  - In several medical centers computed radiography has almost completely replaced
      the use of conventional screen-film systems for general radiography. The aim of
      this paper is to explain the basic principles of the four most frequently
      numerical detectors used in the world, with emphasis on the phosphor plates,
      which are the most frequently used both in hospitals and by practitioners. The
      other two systems are based on a receptor with selenium. The fourth uses charged
      coupled device (CCD) detectors. The most important principles of digital
      processing are then described with concentration on unsharp mask filtering. In
      the future computed radiography will replace standard radiology and will create a
      system in medicine using the power of computers to archive--with more efficiency
      and less space--patient medical data. The transmission of data to workstations
      and the processing of this data is the topic of a new field in medicine.

PMID- 9755798
TI  - Fat suppression techniques in MRI: an update.
AB  - Due to short relaxation times, fat has a high signal on magnetic resonance images
      (MRI). This high signal, easily recognized on MRI, may be useful to characterize
      a lesion. However, small amounts of lipids are more difficult to detect on
      conventional MRI. In addition, the high signal due to fat may be responsible for
      artifacts such as ghosting and chemical shift. Lastly, a contrast enhancing tumor
      may be hidden by the surrounding fat. These problems have prompted development of
      fat suppression techniques in MRI. Fat may be suppressed on the basis of its
      difference in resonance frequency with water by means of frequency selective
      pulses or phase contrast techniques, or on the basis of its short T1 relaxation
      time by means of inversion recovery sequences. Lastly, hybrid techniques
      combining several of these fat suppression techniques are also possible. The aim
      of this paper is to review the basic principles of all these fat suppression
      techniques and to exemplify their clinical use.

PMID- 9755799
TI  - Materials and biomaterials for interventional radiology.
AB  - Devices used in interventional radiology have significantly developed in the past
      few years. In order to understand the trends of this development, we analyzed how
      new interventional devices are progressively incorporating materials having
      original physical properties, and how developers are today progressively turning
      towards biomaterials, with respect to the new regulatory environment, and the
      requirements of biocompatibility.

PMID- 9755800
TI  - Novel implications of the potential role of selenium on antioxidant status in
      streptozotocin-induced diabetic mice.
AB  - Levels of blood glucose, lipid peroxidation, glutathione (GSH), glutathione
      peroxidase (GPx), glutathione S-transferase (GST) activities and blood selenium
      levels were determined in streptozotocin (STZ)-induced diabetic mice. The effect
      of oral administration of sodium selenite was studied on the above parameters.
      Diabetes caused hyperglycemia (2.8-fold increase) with a significant increase in
      the malondialdehyde levels (89% in liver and 83% in blood) and GST activity (55%)
      and marked decreases in GSH levels (approximately 73% in blood and 79% in liver)
      in the 5th week after STZ treatment as compared to normal control animals.
      Treatment of STZ-induced diabetic mice with sodium selenite changed these
      parameters to near control values in almost all cases. These results suggest that
      selenium plays a role in reducing the oxidative stress associated with diabetes.

PMID- 9755801
TI  - Possible respect of patient quality of life--without reducing survival expectancy
      -in breast cancer treatment.
AB  - The treatment of breast cancer by some doctors in all countries and all in some
      does not concern itself with quality of life considerations. Partial breast
      cancer surgery is possible in cases of neither voluminous nor central tumors, and
      surgery can also be partial after pre-surgical chemotherapy reduction. The
      apoptotic test for cytostatic choice should assist in obviating toxicities which
      are minor for the physician, i.e., alopecia, cardiac lesion, etc, but which are
      major for the patient. Cytostatics will be useless in treatment if they are not
      apoptogenic. Hormonal treatment may, when there are estrogen receptors involved,
      be advantageously combined with chemotherapy. In estrogen receptors absence,
      growth factor receptors should be considered, as there is a possible indication
      of somatostatin analogs (instead of hormones, which are useless). Quality of life
      is mainly determined by the partial character of the surgery, hence by the volume
      and localization of the tumor. Cancer screening allows diagnosis when tumors are
      smaller as opposed to those which are the object of spontaneous diagnosis. We
      even propose screening of dysplasias and their biological treatment between 40
      and 50 years--hormonal if the specific cells carry hormone receptors, and based
      on somatostatin analogs if they carry growth factor receptors.

PMID- 9755802
TI  - The clinical role of growth factors in the treatment of breast cancer.
AB  - Growth factors have had an increasingly strong impact in breast cancer management
      in recent years. The main role of growth factors, particularly hematopoietic
      growth factors, in this setting has been to promote better tolerance of standard
      doses, and for the implementation of high-dose chemotherapy in innovative
      protocols. After a brief overview of growth factor biology, the current clinical
      guidelines for their use in cancer management is reviewed. Finally, the role
      growth factors in palliative and curative chemotherapy of breast cancer and
      methods to reduce tumor cell contamination of peripheral stem cell harvests will
      be discussed.

PMID- 9755804
TI  - Primary chemotherapy in breast cancer.
AB  - Primary (neoadjuvant) chemotherapy is a rapidly evolving area in the management
      of early operable breast cancer. This approach achieves significant responses in
      around 80% of patients, with a reduction in the need for immediate mastectomy in
      patients presenting with large primaries, with no evidence of increased local
      recurrence. So far randomised trials suggest that survival is as good with
      primary chemotherapy as with post-operative adjuvant chemotherapy. Primary
      chemotherapy offers the potential short term tumour response as a predictor for
      longer term survival. More importantly, it allows serial biological measurements
      of treated breast cancers which, in turn, may aid the selection of appropriate
      treatment for individual patients and allow the rapid assessment of new
      therapies.

PMID- 9755803
TI  - Diet and risk of breast cancer: major findings from an Italian case-control
      study.
AB  - A large case-control study (2,569 women with breast cancer and 2,588 control
      women) carried out in Italy between 1991 and 1994 permits elucidation of breast
      cancer risk in relation to dietary patterns in a southern European population.
      Major findings include direct associations with the intake of bread and cereal
      dishes, sugar, and pork meat, and inverse associations with the intake of
      vegetable oils, raw vegetables, fish, beta-carotene, vitamin E, and calcium.

PMID- 9755805
TI  - New endocrine approaches in the treatment of breast cancer.
AB  - As a result of tamoxifen becoming the first endocrine compound with proven
      activity in breast cancer, a. broad spectrum of new substances have been tested
      and several are now available for clinical use. New pure antiestrogens show no
      estrogenic activity as a result of different receptor binding, and some other
      derivatives of tamoxifen demonstrate varied toxicity profiles. The second and
      third generation of aromatase inhibitors can selectively inhibit the aromatase
      enzyme in the peripheral tissue and perhaps even in tumor cells. Gonadotrophin
      releasing hormone (GnRH)-analogues can suppress ovarian function in premenopausal
      patients and thus prevent surgical ovarectomy. The value of a new group of anti
      progestional substances has not yet been clarified. In this overview the most
      important compounds are reviewed for efficacy and toxicity in breast cancer
      patients.

PMID- 9755806
TI  - A review of breast cancer chemoprevention.
AB  - Breast cancer remains a major cause of mortality and morbidity, and may be
      amenable to chemoprevention as estrogen stimulation is believed to be responsible
      for the promotion of this disease. Tamoxifen is the most widely studied compound
      for chemoprevention and clinical trials involving over 20,000 women world-wide
      are currently underway. This drug is well-tolerated with low acute toxicity and
      high compliance, and has a favorable profile in both decreasing serum cholesterol
      and increasing bone mineral density in postmenopausal women. However, there are
      fears of its potential carcinogenicity, especially an increased risk of
      endometrial cancers, which may jeopardize further recruitment and compliance of
      women in these chemoprevention studies. Meta-analyses of these studies are
      expected to be conducted in the year 2000 to address the efficacy of tamoxifen in
      women with an increased familial predisposition and in those with known germline
      BRCA mutations.

PMID- 9755807
TI  - Suppression of alloreactivity with gamma delta T-cells: relevance to increased
      gamma delta T-cells following bone marrow transplantation.
AB  - Several reports have shown that an increase in T-cell receptor gamma/delta
      positive T-cells (gamma delta T-cells) have been observed following bone marrow
      transplantation. gamma delta T-cells expanded from peripheral blood mononuclear
      cells from normal volunteers were used to investigate the function of gamma delta
      T-cells in vitro. Peripheral blood mononuclear cells were cultured with synthetic
      ligand of gamma delta T-cells, monoethyl phosphates (MEP), for 7 days. MEP
      specifically expanded gamma delta T-cells. Expanded gamma delta T-cells from
      subject "B" were added to an A anti-B or A anti-C mixed lymphocyte culture (MLC)
      containing responder cells from subject "A" and irradiated stimulator cells from
      subjects "B" or "C". The cultures were harvested on day 6 and tested for
      cytotoxicity against stimulator-type Con A blasts. gamma delta T-cells from
      subject "B" specifically inhibit generation of allospecific cytotoxic T
      lymphocytes (CTL) in A anti-B MLC. The results indicate that gamma delta T-cells
      exhibit veto-type suppression of alloreaction. If the current experiments are
      also applicable in vivo, gamma delta T-cells originating from the donor after
      bone marrow transplantation may inhibit graft rejection by suppressing recipient
      anti-donor reactivity. gamma delta T-cells may be involved in the suppression of
      allogeneic reaction in vivo following allogeneic bone marrow transplantation.

PMID- 9755808
TI  - Mode-actions of the Na(+)-Ca2+ exchanger: from genes to mechanisms to a new
      strategy in brain disorders.
AB  - Mode-actions of the Na(+)-Ca2+ exchanger from genes to mechanisms to a new
      strategy for brain disorders were comparatively studied in oxidative stress. In
      transfected Chinese hamster ovary (CHO) cells steadily expressing the Na(+)-Ca2+
      exchanger's gene, Ca(2+)-efflux via an active mode of the Na(+)-Ca2+ exchanger
      was elicited by hydrogen peroxide (H2O2) after preincubation of the cell with a
      Ca(2+)-free medium, whereas Ca(2+)-influx via a reverse mode of the Na(+)-Ca2+
      exchanger was dramatically evoked by H2O2 after preincubation of the cell with a
      Ca2+ medium, as a prelude to neuronal death. According to [45Ca2+] uptake of
      transfected CHO cells at given time intervals or extracellular Na+[Na+]o
      gradients, hyperbola, logarithmic and sigmoid curve equations of the Na(+)-Ca2+
      exchanger's mode-actions were respectively defined in the absence and the
      presence of H2O2. The Na(+)-Ca2+ exchanger's conformational transition in
      oxidative stress was dominated by adenosine triphosphate (ATP)-dependent
      cytoskeletal redox modification, cation-pi interactions and secondary Ca2+
      activation. These mechanisms were used to generate an intracellulary distributed
      tetra-cluster (named VISA931) for rescuing G-protein agonist-sensitive signal
      transduction and cortico-cerebral somatosensory evoke potential (SEP) from
      oxidation via activating forward operation of the Na(+)-Ca2+ exchanger, the beta
      adrenergic and the P2-purinergic receptors, blocking Ca2+ influx and catalyzing
      the dismutation of superoxide anions (O2-.) to H2O2. In conclusion, knowledge
      based drug design is a new strategy for developing promising candidates of
      neuroprotective agents.

PMID- 9755809
TI  - Effect of pyridoxal 5'-phosphate on human neutrophil respiratory burst and
      adhesion on serum coated microplates.
AB  - The effect of pyridoxal 5'-phosphate (PP) on human polymorphonuclear leukocytes
      respiratory burst and on cellular adhesion on serum coated microplates was
      investigated. No dose-response effect was observed after 10 min pre-treatment at
      37 degrees C of human neutrophils with increasing doses of PP, ranging from 0.05
      mM/L to 0.5 mM/L. The production of superoxide anion (O2-), after challenging
      cells with 0.5 pM/L formyl-methyonyl-leucyl-phenylalanine, 50 ng/mL phorbol
      myristate acetate or 50 pg/mL concanavalin A was comparable to that observed by
      pre-treating cells with phosphate buffered saline only (control, no PP),
      therefore indicating that PP did not affect neutrophil respiratory burst in our
      assay conditions. Evaluation of the effect on cellular adhesion onto fetal bovine
      serum pre-coated microplates produced the same results. As previous results
      showed that PP in the range of 0.01 mM/L to 0.6 mM/L proved to be an efficient
      inhibitor of neutrophil aggregation, the evidence reported here might contribute
      to establish PP as a good in vitro leukocyte anti-aggregant which does not affect
      other functional parameters.

PMID- 9755810
TI  - Protective effect of Crassostrea gigas extract on audiogenic seizures in
      magnesium deficient mice.
AB  - Audiogenic seizures associated with loss of weight, prostration, piloerection,
      palpebral ptosis and motor deficiency were induced after sound stimulation of
      determined frequency and amplitude in magnesium-deficient DBA/2 mice. These
      symptoms were maintained when standard diet conditions (1700 ppm Mg2+) were
      restored. In contrast, mice were protected from audiogenic seizure in a dose
      related manner when Crassostrea gigas extract (JCOE) were added to the diet for
      10 consecutive days. Although a rational explanation for this protective effect
      has not yet been determined, it is assumed that it might be due to a chelating
      complex formed between Mg2+ and taurine, which enhance the uptake of Mg2+.

PMID- 9755811
TI  - Relation between the osmolality trend and ornithynedecarboxylase activity in red
      blood cells of uremic patients during hemodialytic treatment.
AB  - In uremic patients during chronic hemodialysis an increase in the volume of red
      blood cells is observed. Contemporaneously there is an increase in
      intraerythrocytic ornithynedecarboxylase activity beyond the normal content (P <
      0.01), a high level of seric and plasmatic polyamines (P < 0.01) and a decrease
      in seric osmolality (P < 0.01) with pH improvement. The trends of osmolality,
      ornithynedecarboxylase, mean cell volume and pH are significantly related. Our
      data support the hypothesis that, during hemodialysis, red blood cell volume
      changes and increased ornithynedecarboxylase activity are dependent on the
      general improvement of plasma tonicity. Moreover, the absence of inhibition of
      ornithynedecarboxylase activity by high levels of putrescine is noted.

PMID- 9755812
TI  - Relationship between amine-carboxyboranes and TNF alpha for the regulation of
      cell growth in different tumor cell lines.
AB  - The amine-carboxyboranes were shown to be synergistic with tumor necrosis factor
      alpha (TNF alpha) in cytotoxicity and inhibition of DNA synthesis in select types
      of cancer cells depending on the presence of a TNF alpha high affinity receptor
      on the membrane of the cell. Initially both TNF alpha and the amine
      carboxyboranes reduce the influx of calcium but later cause a significant
      increase intracellularly. This influx is not linked with the amine-carboxyborane
      activating the calcitonin receptor in the tumor cells. Neither the agents nor TNF
      alpha directly inhibits DNA topoisomerase II activity but both did cause
      decreased phosphorylation of the enzyme by protein kinase C (PKC). The two agents
      caused synergistic inhibition. This event correlated with increased DNA protein
      linked breaks, DNA fragmentation and cell death. These protein linked breaks are
      additive with etoposide's effects but the latter agent's mechanism is different
      than phosphorylation of topoisomerase II. There was no evidence that the DNA
      fragmentation was caused by a calcium induced endonuclease enzyme in these cancer
      cells. The low-molecular weight amine-carboxyboranes appear to play an identical
      function as TNF alpha in its role to cause DNA breaks and fragmentation to cause
      apoptosis.

PMID- 9755813
TI  - Ca2+ dependent purinergic regulation of p42 and p44 MAP kinases in astroglial
      cultured cells.
AB  - Adenosine triphosphate (ATP) is a signaling molecule for brain cells including
      astrocytes. In these cells, it has been shown that ATP stimulates myelin basic
      protein (MBP) kinase activity which is believed to represent the Erk family of
      MAP kinases. Indeed, we show that ATP activates simultaneously MBP kinase
      activity and phosphotyrosine incorporation in p42 Erk2 and p44 Erk1. Maximal
      effect of ATP is obtained at 50 microM after 5 min and disappears after 60 min.
      Effect of ATP is mimicked by 2-methylthio-ATP whereas alpha beta
      methyleneadenosine 5' triphosphate (AMP-CPP) and adenosine do not promote any
      effect. Uridine triphosphate (UTP) activates also p42 and p44 MAP kinases. These
      observations indicate that p42-p44 MAP kinases activation can be obtained through
      P2v and P2u receptors. Purinergic stimulation of Erk is insensitive to pertussis
      toxin which inactivates heterotrimeric Gi protein. It is not inhibited by a PLA2
      inhibitor (4 bromophenacyl bromide [B phi B]) and the PI3 kinase inhibitor,
      wortmannin. In contrast, purinergic stimulation of Erk is partially inhibited by
      the PKC inhibitor. GF109203X, at 5 microM and suppressed when extracellular
      calcium is complexed by ethylene glycol-bis(2-aminoethyl ether)-N,N,N',N'
      tetraacetic acid (EGTA).

PMID- 9755814
TI  - Iatrogen male infertility.

PMID- 9755815
TI  - Genetic diseases of the seminal ducts.
AB  - Azoospermia due to an obstruction of the genital tract is one of numerous
      possible pathophysiologic mechanisms underlying male infertility. The blockage of
      the seminal ducts may be acquired or congenital. Only recently has the strong
      association between mutations in the cystic fibrosis transmembrane conductance
      regulator (CFTR) gene and various subtypes of obstructive azoospermia been
      elucidated. Most patients with congenital bilateral absence of the vas deferens
      or bilateral ejaculatory duct obstruction are carriers of such mutations. The
      relationship between abnormal CFTR alleles and unilateral absence of the vas
      deferens, isolated seminal vesicle anomalies, and Young syndrome is less well
      characterized and awaits further investigation.

PMID- 9755816
TI  - Ethical aspects of in vitro fertilization and embryo transfer.
AB  - In vitro fertilization and embryo transfer (IVF-ET) confronts moral reflection
      with a wide range of concerns. Some are similar to those raised by artificial
      insemination such as the procurement of sperm, the goods of marriage and donor
      gametes. Others are unique to IVF-ET such as surrogacy, the status of the embryo
      and cryopreservation.

PMID- 9755817
TI  - Somatostatin release in response to glucose is impaired in chronic renal failure.
AB  - In order to evaluate somatostatin (SRIH) secretion in uremia, plasma SRIH
      concentrations were determined in basal conditions and after an oral glucose
      tolerance test (OGTT) in 14 non-dialysed patients with chronic renal failure
      (CRF), seven of whom had normal glucose tolerance (NGT) and seven impaired
      glucose tolerance (IGT). Plasma insulin, C-peptide and glucagon and blood glucose
      concentrations were also evaluated. The results were compared with those obtained
      in a group of age- and sex-matched normal subjects. In CRF patients, plasma SRIH
      fasting values (8.6 +/- 0.6 and 7.8 +/- 0.6 pmol/L in NGT and IGT patients,
      respectively) were comparable to those recorded in controls (7.7 +/- 0.5 pmol/L).
      SRIH response to OGTT, evaluated as area under curves (AUC) above basal, was
      similar in both groups of CRF patients (412.9 +/- 84.5 and 415.6 +/- 51.9 pmol/L
      per min), and significantly lower than in controls (660.1 +/- 58.5 pmol/L per
      min). Data indicate that chronic uremia induces a loss of SRIH secretory cell
      responsiveness to glucose. A possible effect of impaired SRIH secretion on
      glucose metabolism in CRF is discussed.

PMID- 9755818
TI  - GABA modulates cytotoxicity of immunocompetent cells expressing GABAA receptor
      subunits.
AB  - C57 black mouse splenic T lymphocytes effector cells were co-cultivated with
      Balb/c mouse splenic cells for sensitization; P815 DBA mouse mastocytoma target
      cells were then added and specific T cell-dependent cytotoxicity determined. This
      cytotoxicity increased after gamma-aminobutyric acid (GABA) treatment of the
      sensitized effectors, but decreased after GABA treatment of the targets. These
      GABA effects seemed to be specific since they were partially mimicked by linear
      but not ramified GABA analogues. Furthermore, they were likely mediated by GABAA
      receptor since GABAA receptor subunit mRNAs and protein could be demonstrated in
      effector or target immune specific cells, suggesting that under yet to be defined
      circumstances, GABA may affect T cell functions.

PMID- 9755819
TI  - Epidemiological study of p53 tumor suppressor gene mutations in patients from
      Luxembourg and the German Saar region with an advanced colorectal cancer using
      PCR-SSCP analysis.
AB  - Mutations in the p53 tumor suppressor gene are usually associated with an
      advanced development of colorectal cancer characterized by the transition from
      the adenoma to the carcinoma stage. We used the polymerase chain reaction (PCR)
      followed by single-strand conformation polymorphism (SSCP) analysis to screen for
      the presence of mutations in the p53 gene of patients from Luxembourg and the
      German Saar region with colorectal cancers at various developmental stages. While
      we detected no mutations in 16 colic polypi at an early to intermediate stage
      (adenoma), we revealed seven (13.7%) non-silent point mutations (transitions) in
      exons 5 to 9 of the p53 gene in 51 colorectal tumors at a late stage (carcinoma).
      In addition to confirming previous observations, these results show that PCR-SSCP
      analysis can provide both a sensitive and rapid method for the genetic
      determination of the histopathological stage of colorectal samples.

PMID- 9755821
TI  - Ajoene [(e,z)-4,5,9-trithiadodeca-1,6,11-triene 9 oxide] does not exhibit
      antiviral activity at subtoxic concentrations.

PMID- 9755820
TI  - Selective in vitro protection of SIVagm-induced cytolysis by ajoene, [(E)-(Z)
      4,5,9-trithiadodeca-1,6,11-triene-9 oxide].
AB  - We studied the effect of synthetic ajoene on simian immunodeficiency virus
      (SIVagm)-mediated cell fusion and subsequent virus-induced cytolysis. Our data
      indicate that this compound is a strong antifusion agent with a 50% syncytium
      inhibitory concentration (SIC50%) value of about 2.9 microM. We suggest that
      ajoene interacts with the cell-specific integrin molecules and sterically hinders
      the association between fusion (or other co-receptors) and the CD4-gp120 complex
      at the cell surface of SIV-infected cells. Although ajoene was maximally
      effective in suppressing syncytium formation during the early period (ie, up to 6
      h) of the fusion process, when the compound was recurrently added to the co
      cultures, the inhibitory effect was regained and further cell death was markedly
      delayed. This indicates that ajoene was also effective after the initial cell-to
      cell contact stage. These data suggest that ajoene may be a promising approach
      for the treatment of SIV/human immunodeficiency virus (HIV) infections.

PMID- 9755822
TI  - The cells are mortal or immortal, divide and disappear with reincarnation or
      after metabolic or apoptotic death.

PMID- 9755823
TI  - The central role of the mitochondrial megachannel in apoptosis: evidence obtained
      with intact cells, isolated mitochondria, and purified protein complexes.
AB  - The mitochondrial megachannel (also called permeability transition pore) is a
      polyprotein complex formed in the contact site between the inner and the outer
      mitochondrial membranes and participates in the regulation of mitochondrial
      membrane permeability. We have obtained three independent lines of evidence
      suggesting the implication of the mitochondrial megachannel in apoptosis. First,
      in intact cells, apoptosis is accompanied by an early dissipation of the
      mitochondrial transmembrane potential (delta psi m). In several models of
      apoptosis, specific agents inhibiting the mitochondrial megachannels prevent this
      delta psi m dissipation and simultaneously abolish the manifestations of caspase-
      and endonuclease activation, indicating that megachannel opening is a critical
      event of the apoptotic process. Second, mitochondria are rate-limiting for
      caspase and nuclease activation in several cell-free systems of apoptosis.
      Isolated mitochondria release apoptogenic factors capable of activating pro
      caspases or endonucleases upon opening of the mitochondrial megachannel in vitro.
      Third, opening of the purified megachannel reconstituted into liposomes is
      inhibited by recombinant Bcl-2 or Bcl-XL, two apoptosis-inhibitory proteins which
      also prevent megachannel opening in cells and isolated mitochondria. This
      indicates that the megachannel is under the direct regulatory control of anti
      apoptotic members of the Bcl-2 family. Altogether, our results suggest that
      megachannel opening is sufficient and (mostly) necessary for triggering
      apoptosis.

PMID- 9755824
TI  - Importance of DNA fragmentation in apoptosis with regard to TUNEL specificity.
AB  - In the absence of a universal specific molecular tracer of apoptosis, structural
      DNA alterations provide the basis of labeling systems: double-strand
      fragmentation for TUNEL (terminal transferase-mediated dUTP nick end-labeling),
      denaturation for poly (A) in situ hybridization, immunogenicity of single strand
      DNA, all methods which imply limited specificity due to the unavoidable presence
      of DNA breaks in virtually all cells. Thus, TUNEL application has been restrained
      to a narrow spectrum of sample conditions which has limited, in particular,
      retrospective surveys and apoptotic nuclei-protein double labelings. In the
      apoptotic nucleus two main obstacles intervene between TUNEL reagents and their
      targets: DNA hypercondensation and proteins around DNA. The former increases in
      the course of apoptosis and both are worsened by crosslinking and precipitating
      fixatives. This point out that TUNEL is an ambitious approach whose target,
      apoptotic DNA breaks, is less accessible than breaks occurring in non-apoptotic
      less compacted DNA. However, TUNEL has an advantage: the far greater degree of
      apoptotic DNA fragmentation. How to obtain a frank differential staining between
      apoptotic and non-apoptotic DNA? It appears that the answer relies on the
      pretreatment step and not in modifying the TUNEL staining protocol, which is
      optimal. Adapted pretreatments are able to circumvent accessibility obstacles and
      to extend TUNEL applicability to the most demanding conditions, those of archived
      tissue samples and of TUNEL--protein double labelings.

PMID- 9755825
TI  - Apoptosis and liver fibrosis: antifibrotic strategies.
AB  - Hepatic fibrosis is a frequent response of the liver and is similar to
      parenchymal wound healing in other tissues. Apoptosis has been described in
      different models of liver fibrosis. Hepatic stellate cells are the main source of
      extracellular matrix. At present, one can speculate that inhibition of apoptosis
      is responsible for activation and proliferation of hepatic stellate cells. Thus,
      the inhibition of hepatic stellate cell apoptosis could be a target for
      antifibrotic strategies. Until now, no drugs have been clearly shown to be
      effective in reducing specifically the development of hepatic fibrosis. However,
      serious candidates are presently under studies in clinical trials, including
      especially alpha interferon and phosphatidylcholine.

PMID- 9755826
TI  - Apoptosis and programmed cell death: a role in cerebral ischemia.
AB  - Hypoxic-ischemic neuronal death has long been considered to represent necrosis,
      but it now appears that many brain neurons undergo apoptosis after either global
      or focal ischemic insults. Recent studies demonstrated: 1) DNA cleavage into
      oligonucleosome-sized fragments demonstrated by a typical ladder pattern; 2)
      early endonuclease activation, as demonstrated by the presence of high molecular
      weight DNA fragments (300 to 50 kbp); 3) chromatin condensation and apoptotic
      bodies formation; 4) activation of apoptosis-associated proteins. These results
      may indicate that apoptosis contributes to the development of the ischemic
      infarct and is probably substantially distinct from ischemia-triggered
      excitotoxicity, which tends to produce necrosis.

PMID- 9755827
TI  - 3-Bromoacetylamino benzoylurea (3-BAABU), a new antimicrotubule cancericidal
      agent applied in cytogenetic analysis in hematology.
AB  - 3-Bromoacetylamino benzoylurea (3-BAABU) is a newly synthesized antimicrotubule
      cancericidal compound. In the present study, we investigated the possibility of
      using 3-BAABU as a mitotic blocking agent for hematologic karyotyping. Treatment
      with 3-BAABU caused scattering of metaphase chromosomes throughout the cytoplasm
      both in phytohemagglutinine (PHA)-stimulated human lymphocytes and in human
      leukemic cells. Kinetic showed a rapid uptake of 3-BAABU by treated cells and
      irreversibility of its effect. Using 3-BAABU in routine procedure, a karyotype of
      lymphocytes from a normal male was 46, XY, with normal structure and CEM leukemic
      line was 85, XX, in a representative spread with abnormalities similar to reports
      using other blocking agents. Using 3-BAABU in spectral karyotyping, details of
      translocations in CEM leukemic cells were readily detected in several
      chromosomes, such as 7 [t(7;11)], 8 [t(8;9)], 9 [t(8;9) & t(9;19)], 11 [t(7;11)],
      16 [t(16;18;20)] and 20 [t(1;20)]. 3-BAABU displayed two important characters in
      cytogenetics, 1) it caused dispersion of chromosomes, avoiding chance of overlap;
      2) compared to the conventional mitotic blocking agent, vinblastine sulfate, 3
      BAABU exhibited much gentle effect on chromosomes, thus providing more
      flexibility in time to perform karyotyping.

PMID- 9755828
TI  - Structurally different anthracyclines provoke different effects on cell cycle and
      tumor B cell differentiation.
AB  - Previously we have detected a stimulatory effect on immunoglobulin (IgG)
      synthesis when hybridoma cells were treated with doxorubicin. In order to
      determine whether this is a general property of anthracycline, we have selected
      three analogs--doxorubicin (DOX), pirarubicin (THP-DOX) and aclarubicin (ACR)-
      which differ mainly in the methylation state of their amino sugars. Cell cycle
      analysis by flow cytometry and drug localization by scanning confocal microscopy
      were also performed. The results show that when cells (UN2 hybridoma B cells),
      were exposed to subtoxic doses of DOX or THP (with unmethylated amino sugars), a
      strong increases in IgG secretion, heavy (H) and light (L) chain synthesis and
      the corresponding mRNA levels were induced. Furthermore these two drugs arrested
      the cells in the G2/M phase of the cell cycle. In contrast, exposure to ACR (with
      its methylated amino sugar) at similar subtoxic doses induced a blockade of cells
      in the G1 phase with no increase of IgG synthesis, at the subtoxic doses used,
      all three drugs could still be detected in the nucleus as well as in the
      cytoplasm, as determined by confocal laser microscopy. Thus, the relationship
      between cell cycle blockade, IgG stimulation and anthracycline structure is
      suggested by these results.

PMID- 9755829
TI  - [Laboratory and clinical studies on tazobactam/piperacillin in the field of
      pediatrics].
AB  - Laboratory and clinical studies on tazobactam/piperacillin (TAZ/PIPC), a
      combination drug of piperacillin (PIPC) with the new beta-lactamase inhibitor
      tazobactam (TAZ), were carried out in the field of pediatrics. 1. After
      intravenous administration of TAZ/PIPC at a dose of 25 mg/kg to one child, the
      peak plasma levels of TAZ and PIPC were 24.4 micrograms/ml and 119 micrograms/ml
      respectively after 5 min. The half-lives of TAZ and PIPC were 0.48 and 0.60 hours
      respectively. Same as 50 mg/kg to two children, the peak plasma levels of TAZ and
      PIPC were 17.5, 32.2 micrograms/ml and 92.8, 163 micrograms/ml after 5 min. The
      half-lives of TAZ and PIPC were 0.37, 0.50 hours and 0.51, 0.59 hours. A ratio of
      TAZ to PIPC was about 1 to 4 in plasma levels. The cumulative urinary recovery
      rates of TAZ and PIPC in the first 6 hours after intravenous administration were
      15.8, 64.9% and 39.8, 53.4%. 2. The antibacterial activity of TAZ/PIPC against
      clinically isolated organisms was determined. The MICs of TAZ/PIPC were < or =
      0.05 microgram/ml against Haemophilus influenzae and Streptococcus pneumoniae and
      > or = 1.56 micrograms/ml against Escherichia coli, Staphylococcus aureus and
      Haemophilus parainfluenzae. 3. The clinical efficacy of TAZ/PIPC could be
      evaluated in 14 patients with various bacterial infections, and was evaluated as
      "excellent" in 9 patients and as "good" in 5. The overall clinical efficacy rate
      in 14 cases was 100% and excellent was 64.3%. Bacteriological efficacy rate was
      91.7% (10/11). 4. As a side effect, loose stool was observed in one case, no
      abnormal laboratory test values were observed. It has been concluded that
      TAZ/PIPC was a useful drug in the field of pediatrics.

PMID- 9755830
TI  - [Fundamental and clinical studies on tazobactam/piperacillin in the pediatric
      field].
AB  - Pharmacokinetics, efficacy and safety of tazobactam/piperacillin (TAZ/PIPC), a
      new beta-lactamase inhibitor combined with a penicillin antibiotic, were studied
      in pediatrics and the following results were obtained. 1) Serum concentration and
      urinary excretion of TAZ/PIPC after intravenous administration at a dose of 46
      mg/kg to one child were investigated. Serum half-lives were 0.5 hours for TAZ and
      0.6 hours for PIPC, while the urinary recovery rates in the first 6 hours after
      administration, were 61.6% and 56.3% respectively. 2) TAZ/PIPC was administered
      at a dose of 46.0-73.5 mg/kg t.i.d. for 3-13 days to 10 patients, 6 with
      respiratory infection, 1 with pharyngotonsillitis, 1 with pertussis and 2 with
      soft tissue infection of skin. Clinical response were excellent in 5 cases and
      good in 5 cases, and the efficacy rate was 100%. Bacteriologically, 2 strains
      (Staphylococcus aureus and Streptococcus pyogenes) isolated from 2 patients were
      eradicated after the treatment. As for adverse reaction, mild skin rash was
      observed in 1 case but disappeared within 2 days after withdrawal of the drug. As
      for abnormal laboratory test results decrease in neutrophiles and increase in
      eosinophiles in each 1 case were observed, which were, however, normalized after
      administration. From the above results, tazobactam/piperacillin was considered to
      be a useful antibiotic in the pediatric field.

PMID- 9755831
TI  - [Basic and clinical studies on tazobactam/piperacillin in pediatric field].
AB  - A drug susceptibility test of the combination drug TAZ/PIPC, which consists of a
      newly developed beta-lactamase inhibitor, tazobactam (TAZ), and one of penicillin
      antibiotics, piperacillin (PIPC), with combination ratio of 1:4 in potency, was
      conducted with stock strains and clinical isolates. The clinical efficacy and
      safety of its injection was also evaluated in children with a variety of
      infectious diseases. The results were as follows: 1. In susceptibility test, 114
      strains from 4 species of stock strains were treated with 8 drugs, that is,
      TAZ/PIPC, PIPC, penicillin G (PCG), ampicillin (ABPC), cefotiam (CTM), cefotaxime
      (CTX), ceftazidime (CAZ), and sulbactam/cefoperazone (SBT/CPZ). Of three
      clinically isolated species from patients, Staphylococcus aureus (S. aureus) was
      treated with TAZ/PIPC, PIPC, methicillin (DMPPC), CTM, CTX, and SBT/CPZ, and the
      others were treated with the same drugs except for DMPPC. The MICs were measured
      for these bacterial strains inoculated at the concentration of 10(6) CFU/ml. The
      MIC90 values of TAZ/PIPC against 45 strains of Streptococcus pyogenes (S.
      pyogenes), one of the stock cultures of Gram-positive cocci, were 0.05
      microgram/ml and similar to those of PIPC, CTM, CAZ, and SBT/CPZ. The MICs of
      TAZ/PIPC for 28 strains of Streptococcus agalactiae (S. agalactiae) were 0.39
      microgram/ml and similar to those of PIPC, CTM, CAZ, and SBT/CPZ. As for Gram
      negative bacilli, the MIC90 of TAZ/PIPC against 10 strains of Bordetella
      pertussis (B. pertussis) were 0.10 microgram/ml and similar to those of PIPC. The
      MIC90 of TAZ/PIPC against 31 strains of Haemophilus influenzae (H. influenzae)
      were 0.05 microgram/ml and similar to those of PIPC, CTX, and SBT/CPZ. Regarding
      Gram-positive cocci isolated from patients received this combination drug, the
      MIC90 of TAZ/PIPC against 2 strains of S. aureus, a non beta-lactamase producing
      strain and a low-beta-lactamase producing strain, were 0.78 microgram/ml and 3.1
      micrograms/ml, respectively; the former value was similar to those of PIPC,
      DMPPC, CTM, and CTX, and the latter was similar to those of PIPC, DMPPC, CTX, and
      SBT/CPZ. Of 4 strains of Streptococcus pneumoniae, 2 strains were inhibited at
      0.05 microgram/ml, and the others at 1.56 micrograms/ml; both values were similar
      to those of PIPC, SBT/CPZ. As for Gram-negative bacilli, 6 of 7 strains of H.
      influenzae did not produce beta-lactamase and 1 strain was a high producer. The
      MICs of TAZ/PIPC against beta-lactamase nonproducing strains were < or = 0.025
      microgram/ml in 5 strains and 0.39 microgram/ml in 1 strain, and the values were
      similar to those of PIPC and SBT/CPZ. While the MIC of TAZ/PIPC against the high
      beta-lactamase producing strain was 0.78 microgram/ml; similar to that of SBT/CPZ
      and smaller than that of PIPC. 2. The results of clinical effects on 7 diseases
      in 33 cases were as follows: TAZ/PIPC was clinically judged "excellent" in 17
      (51.5%); good in 14 (42.4%); fair in 2 (6.1%). No case with no response was seen
      in this study, and the total efficacy rate of "excellent" and "good" was 93.9%.
      3. Bacteriological effects were evaluated in 17 strains of 4 species, and all of
      them were eradicated. 4. Adverse reactions were judged in 35, which consisted of
      33 in which the clinical effects were evaluated and 2 dropped from this study. Of
      these cases, diarrhea was observed in 4 (11.4%). 5. Laboratory tests revealed an
      increase in platelets in 1 of 32 cases (3.1%), and eosinophilia in 2 of 29 cases
      (6.9%). Biochemical profile showed an increase in GPT alone and abnormal
      increases in both GOT and GPT in 1 each out of 21 cases.

PMID- 9755832
TI  - [Transferability of tazobactam/piperacillin (TAZ/PIPC) to cerebrospinal fluid of
      rabbit with meningitis caused by Staphylococcus aureus].
AB  - The transferability of tazobactam/piperacillin (TAZ/PIPC) to cerebrospinal fluid
      (CSF) was studied employing rabbits with experimental meningitis caused by
      Staphylococcus aureus. 125 or 250 mg/kg of TAZ/PIPC was intravenously
      administered to rabbits with experimental meningitis then concentrations of TAZ
      and PIPC in CSF and serum were measured. In the group to which 125 mg/kg of
      TAZ/PIPC was administered, mean concentration of TAZ in CSF was 7.3 and 2.4
      micrograms/ml at 30 and 60 min after administration, respectively, and concerning
      PIPC, it was 10.1 and 3.5 micrograms/ml, respectively. CSF/serum ratio of TAZ was
      29.4% and 31.4%, respectively, and that of PIPC was 24.3 and 35.6%, respectively.
      In the group to which 250 mg/kg of TAZ/PIPC was administered, mean concentration
      of TAZ in CSF was 16.5 and 12.6% micrograms/ml, respectively, and concerning
      PIPC, it was 25.6 and 18.2 micrograms/ml, respectively. CSF/serum ratio of TAZ
      was 22.1 and 56.1%, respectively, and that of PIPC was 12.2 and 51.9%,
      respectively. Addition of TAZ did not make significant change of transferability
      of PIPC to CSF. Considering the antibacterial effect of TAZ/PIPC against main
      causative organism of meningitis, this agent was thought to be effective for the
      treatment of purulent meningitis.

PMID- 9755833
TI  - Fibrinolytic proteins in apoptotic human umbilical vein endothelial cells.
AB  - Endothelial cells express fibrinolytic proteins including: urokinase (u-PA) and
      tissue type (t-PA) plasminogen activators, type-1 (PAI-1) and 2 (PAI-2)
      plasminogen activator inhibitors, and u-PA receptor (u-PAR). Apoptotic
      endothelial cells detach, potentially forming both local and circulating
      microthrombi in vivo. In this article, apoptotic human umbilical vein endothelium
      was obtained by serum starvation and compared with nonapoptotic cells rescued
      from death with fresh medium containing serum. Antigen levels for t-PA, PAI-1,
      PAI-2, and u-PAR were reduced greatly in apoptosis (p< 0.05). In contrast, u-PA
      levels were similar in apoptotic as compared with rescued cells (p<0.05).
      Radioactive amino acids were used to determine absolute levels of protein
      synthesis and degradation in these cells. Reduced antigen levels likely were due
      to proteolysis as there was 98% total protein degradation and very little protein
      synthesis in apoptotic endothelial cells. Also, u-PA levels in apoptotic
      endothelial cells were not affected by the protein synthesis inhibitor
      cycloheximide. Endothelial cells in inflammatory sites are exposed to cytokines,
      which increase both apoptosis and u-PA levels. Data from this article support the
      idea that maintained u-PA levels in apoptotic endothelium may protect from micro
      thrombosis in inflammatory sites as well as in the circulation.

PMID- 9755834
TI  - The effect of danaparoid sodium (danaparoid) on endotoxin-induced experimental
      disseminated intravascular coagulation (DIC) in rats.
AB  - Danaparoid sodium (danaparoid) is a low molecular weight heparinoid with
      anticoagulation properties, which mainly consists of heparan sulfate. Compared
      with heparin sodium (heparin), danaparoid has a much higher anti-Xa/anti-thrombin
      ratio. We compared the effect of danaparoid on endotoxin-induced experimental
      disseminated intravascular coagulation (DIC) in rats with heparin. A bolus
      injection of endotoxin (10 mg/kg) induced gradual decreases in the platelet
      count, and the plasma fibrinogen, antithrombin III (AT-III) and heparin cofactor
      II levels, as well as an increase in the fibrinogen/fibrin degradation products
      level from 1 to 6 hours after the injection, indicating that both coagulation and
      fibrinolysis were activated. The intravenous administration of danaparoid or
      heparin 3 hours after the endotoxin injection inhibited the endotoxin-induced
      decreases in the platelet count and plasma fibrinogen level and also inhibited
      the endotoxin-induced increase in glomerular fibrin deposition in the kidney.
      Differences between danaparoid and heparin were observed in their effects on the
      plasma AT-III level and clotting time. Danaparoid significantly inhibited both
      the decrease in the plasma AT-III level and the prolongation of the prothrombin
      time induced by endotoxin, where as heparin showed no effect on those responses.
      Moreover, danaparoid enhanced the prolongation of the activated partial
      thromboplast in time induced by endotoxin to a lesser degree than heparin. These
      findings suggest that the effects of danaparoid on the endotoxin-induced decrease
      of the plasma AT-III level and the prolongation of the clotting time are more
      advantageous than those of heparin. The results may have been due to a higher
      anti-Xa/anti-thrombin ratio of danaparoid than that of heparin, indicating that
      danaparoid may be useful in the treatment of DIC.

PMID- 9755835
TI  - A new thromboxane receptor antagonist, Z-335, ameliorates experimental thrombosis
      without prolonging the rat tail bleeding time.
AB  - We investigated the antithrombotic activity of Z-335, a new thromboxane A2
      receptor antagonist, using experimental thrombosis models, and also tested its
      effect on the rat tail bleeding time. Z-335 (0.1, 0.3, and 1 mg/kg, p.o.) dose
      dependently prevented the occurrence of arachidonic acid-induced pulmonary
      thromboembolism in mice. During photochemically induced thrombosis in the femoral
      artery of guinea pigs, Z-335 (0.3, 1, and 3 mg/kg, i.v.) dose-dependently
      prolonged the time required to form thrombi. Moreover, Z-335 (10 mg/kg/day, p.o.)
      strongly suppressed lauric acid-induced hind limb injury in rats. Z-335 (0.3, 3,
      30, and 300 mg/kg, p.o.) did not prolong the tail bleeding time in rats. These
      results strongly suggest that Z-335 ameliorates experimental thrombosis without
      prolonging the rat tail bleeding time, and may therefore be a useful
      antithrombotic drug.

PMID- 9755836
TI  - A randomized comparison of a computer-based dosing program with a manual system
      to monitor oral anticoagulant therapy.

PMID- 9755837
TI  - Relative influence of age and thrombotic history on hemostatic parameters.

PMID- 9755838
TI  - A simple and rapid method for purifying the extracellular domain of human tissue
      factor.

PMID- 9755839
TI  - Clinical significance of serum soluble Fas ligand in patients with acute self
      limited and fulminant hepatitis.
AB  - The Fas ligand (FasL), a member of the tumor necrosis factor family, induces
      apoptosis in Fas-expressing cells. A matrix metalloproteinase-like enzyme cleaves
      the membrane-bound FasL to produce the soluble FasL (sFasL). Since FasL has been
      reported to play a pivotal role in the development of hepatitis, we evaluated
      clinical significance of serum sFasL in acute liver injury including acute self
      limited and fulminant hepatitis. Serum sFasL in 19 patients including 12 with
      acute self-limited hepatitis and 7 with fulminant hepatitis was measured by an
      enzyme-linked immunosorbent assay (ELISA). The clinical data consisted of 18
      indices including age, sex, liver function tests, hepatocyte growth factor (HGF),
      outcome and sFasL. Serum sFasL in fulminant hepatitis is 0.06+/-0.01 ng/ml, being
      identical to that in acute self-limited hepatitis, Serum sFasL is positively
      correlated with AST and ALT (p<0.0001 and p<0.0001). The factors associated with
      outcome of the patients were HGF, albumin, prothrombin time, platelet count,
      cholinesterase and leukocyte count in this order. Serum sFasL serves as an
      indicator of liver injury in acute self-limited and fulminant hepatitis.

PMID- 9755840
TI  - Human colon cancer cells express the functional Fas ligand.
AB  - Fas ligand (FasL) belongs to the TNF superfamily. It is induced in activated
      lymphocytes and eliminates Fas-positive lymphocytes, resulting in the down
      regulation of immune responses. FasL has also been detected in tissues other than
      lymphoid cells. We investigated the expression and function of FasL on human
      colon cancer cells. FasL mRNA was detected by RT-PCR in all six colon cancer cell
      lines tested and was not found on fibroblasts. FasL protein was detected in DLD
      1, LoVo, HCT-116 and RPMI 4788 cells by immunohistochemical staining. DLD-1, LoVo
      and WiDr were cytotoxic against mouse T lymphoma cells which were transfected
      with human Fas receptor cDNA. The cytotoxicity was significantly enhanced by
      phorbol 12-myristate 13-acetate (PMA) and ionomycin. Our data suggest that the
      FasL expressed in human colon cancer cells may be regulated by endogenous factors
      in the microenvironment of the host and facilitates the escape from the host
      immune system.

PMID- 9755841
TI  - The somatostatin analog, octreotide, inhibits in vitro outgrowth of smooth muscle
      cells from canine coronary and carotid atherosclerotic plaque tissues.
AB  - Restenosis is caused by excessive neointima formation resulting from smooth
      muscle cell (SMC) proliferation and migration from the arterial media into the
      subendothelial space, stimulated by growth factors. A long-acting somatostatin
      analog, octreotide, activates protein tyrosine phosphatases and can inhibit the
      stimulatory effects of growth factors. In this study, we evaluated the effect of
      octreotide on SMC outgrowth from in vitro explants of both coronary and carotid
      arterial tissues in a canine endothelium-injury model. After 6 days of culture,
      SMC grew out of 33.3% and 58.3% of the explants from the injured canine carotid
      and coronary arterial tissues, respectively. In contrast, SMC outgrowth was not
      observed from any of the explants from normal canine carotid arterial tissue.
      Octreotide completely inhibited SMC outgrowth from injured canine carotid
      arterial tissue at a concentration of 10(-6) M. This agent also inhibited SMC
      outgrowth from injured canine coronary arterial tissue by 57% and 71% of the
      control value at concentrations of 10(-8) M and 10(-6) M, respectively. We
      conclude that our explant cell-culture model may prove to be valuable for
      assessing the effect of agents designed to reduce intimal proliferation, and that
      the use of the somatostatin analog octreotide in clinical settings may modify the
      high incidence of restenosis after coronary interventions by reducing SMC
      proliferation.

PMID- 9755842
TI  - Ruthenium red inhibits cytosolic Ca2+ oscillations induced by vasopressin in
      primary cultured hepatocytes.
AB  - The effects of ruthenium red were investigated on the vasopressin (Vp)-induced
      Ca2+ response in single, primary cultured rat hepatocytes loaded with fura-2. Low
      concentrations of Vp (1 nM) evoked a sustained train of baseline spike Ca2+
      oscillations, with a latency to first peak of 170 s and a frequency of 0.37 min(
      1). Treatment of hepatocytes with a higher concentration of Vp (10 nM) resulted
      in a rapid rise in intracellular Ca2+, with less delay (40 s), and which remained
      elevated and sustained. Microinjection of a low concentration of ruthenium red
      (10 microM in the injection pipette) altered the observed response to 1 nM Vp
      such that only 2 - 4 base line spikes were observed. A higher concentration of
      ruthenium red (50 microM in the injection pipette) completely abolished the 1 nM
      Vp response. However, the Ca2+ responses to higher concentrations of Vp (10 nM)
      or to the Ca2+-ATPase inhibitor, thapsigargin, were unaffected by ruthenium red.
      These results show that low concentrations of ruthenium red inhibit the Vp
      induced oscillatory Ca2+ response and suggest a contribution of a ryanodine
      receptor-mediated Ca2+-induced Ca2+ release in generating the baseline spike
      oscillations in rat hepatocytes.

PMID- 9755843
TI  - Magnetically induced motor evoked potentials and H-reflex during nembutal and
      ketamine anesthesia administration in rats.
AB  - The effects of nembutal and ketamine anesthesia on motor evoked potentials (MEPs)
      and spinal segment reflex (H-response, F and M waves) were investigated in rats
      by magnetic stimulation. These potentials were generated by magnetic stimulation
      of the motor cortex and the spinal cord (L4-L5). After application of nembutal,
      MEP and H-response decreased in amplitude, eventually disappearing. The
      amplitudes of F and M waves increased and persisted at the increased levels
      during anesthesia. The latencies of F and M waves were constant before and after
      anesthesia. Following ketamine administration, the threshold, latency and
      amplitude of the magnetically induced MEPs, and M, F and H responses were not
      influenced systematically. The results suggested that MEPs and H-response
      depression and/or disappearance due to synaptic site suppression after nembutal
      anesthesia, and the increase and persistence of increased F and M waves
      amplitudes were all due to the increasing motoneuron excitability, whereas
      ketamine did not affect synaptic sites subjected to magnetic stimulation.

PMID- 9755844
TI  - Cell death and cytoskeletal alterations in cultured hepatic fat-storing cells
      induced by 6-hydroxydopamine.
AB  - We studied the effects of the neurotoxin, 6-hydroxydopamine (6-OHDA), on cultured
      fat-storing cells (FSCs) and hepatocytes. If either FSCs or hepatocytes were
      exposed to 6-OHDA for 4 hr, the neurotoxicant induced cell death in FSCs but not
      in hepatocytes. We decided to investigate why hepatocytes were refractile to
      injury from 6-OHDA while FSCs were labile. The activity of antioxidant enzymes
      within FSCs grown in vitro is remarkably lower than the activity in hepatocytes.
      Indeed, some specific antioxidant enzymes in FSCs were undetectable by our
      assays, but were easily detected in hepatocytes. Furthermore, the profile of
      antioxidant activity in FSCs was found to be almost identical to the profiles
      seen in cultured fibroblasts or myocytes. However, indirect immunolocalization of
      tyrosine hydroxylase in FSCs using anti-tyrosine hydroxylase antibodies was
      negative. Mazindol, a dopaminergic receptor antagonist, did not alleviate the
      toxicity of 6-OHDA suggesting that FSCs do not appear to possess a dopaminergic
      receptor. When the cell morphology of FSCs was examined by an indirect
      immunofluorescence technique, treatment of FSCs with 6-OHDA at a concentration of
      200 microM for 2 hr modified the organization of alpha-smooth muscle actin into
      an irregular punctate pattern. Indeed, we found that the effects of 6-OHDA on
      cytoskeletal alterations and on the cell viability of FSCs were irreversible.
      These data suggest that : (1) 6-OHDA can cause irreparable injury to FSCs, but
      not hepatocytes; (2) hepatocytes are specially adapted to withstand an oxidative
      attack in contrast to FSCs. fibroblast and myocytes; (3) FSCs resemble other
      somatic cells in their low levels of antioxidant enzymes; and (4) this low
      profile of antioxidant activity may be responsible for the cell death and
      cytoskeletal alterations observed in FSCs in response to 6-OHDA.

PMID- 9755845
TI  - Role of tumor necrosis factor-alpha in regulating fibrotic lung repair.
AB  - To study the role of tumor necrosis factor-alpha (TNF-alpha) in fibrotic lung
      repair, we evaluated changes in lung TNF-alpha content and binding during the
      evolution of the fibrotic response. We concomitantly examined the effect of TNF
      alpha on lung fibroproliferative responses. Lung TNF-alpha increased early after
      injury, at a time when lung tissue and lung fibroblasts exhibited increased
      binding to the cytokine. Fibroblasts isolated during this phase, which have
      increased spontaneous proliferative activity, had significant reduction in DNA
      synthesis when exposed to TNF-alpha. In contrast, DNA synthesis in normal and
      repair phase fibroblasts was inhibited by TNF-alpha. We also examined mechanisms
      of transduction of the TNF-alpha fibroproliferative signal, and observed that
      phosphorylating enzymes and G-proteins were involved. We conclude that TNF-alpha
      has a dual role in fibrotic repair. During injury, when uncontrolled fibroblast
      proliferation occurs, TNF-alpha production is increased to slow down the
      fibroproliferative response. During repair, when fibroblasts participate in
      structural restitution, TNF-alpha plays a salutary role by stimulating cellular
      proliferation. These effects of TNF-alpha on cellular proliferation are mediated
      by activation of two separate signal transduction pathways, phosphorylating
      enzymes and G-proteins. The observed variability in the effect of TNF-alpha may
      be related to changes in the phenotypic and genotypic characteristics of
      repairing lung fibroblasts which alter their responsiveness to exogenous stimuli.

PMID- 9755846
TI  - No effect of probenecid on the renal excretion mechanism of a new carbapenem, DA
      1131, in dogs.
AB  - The effect of probenecid, an anion transport inhibitor, on the renal excretion
      mechanism of a new anionic carbapenem, DA-1131, was investigated after 1-min
      intravenous infusion of DA-1131, 10 mg/kg, with or without probenecid, 50 mg/kg,
      to dogs. The renal clearance (CL(R)) of DA-1131 in dogs without probenecid
      (3.18+/-0.247 ml/min/kg) was considerably smaller than the reported creatinine
      clearance (CL(CR)) in dogs, 6.13 ml/min/kg, indicating that renal tubular
      reabsorption of the drug was observed in dogs. However, the CLR of DA-1131 was
      not significantly different (3.18+/-0.247 versus 3.29+/-0.698 ml/min/kg) by
      treatment with probenecid indicating that the tubular reabsorption of DA-1131 was
      not inhibited by probenecid.

PMID- 9755847
TI  - Electroporation-mediated gene transfer in cardiac tissue.
AB  - Delivery of genes or macromolecules to cardiovascular tissues provides new
      therapeutic opportunities for the treatment of many acquired and inherited
      diseases. To investigate electroporation as a delivery method in cardiac tissue,
      embryonic chick hearts were studied for uptake of propidium iodide (PI) or DNA
      encoding either green fluorescent protein (GFP) or luciferase following
      electrical shock. PI uptake increased monotonically from 6% of heart tissue after
      3 shocks to 77% with 12 shocks. GFP and luciferase expression varied in
      proportion to shock number, with detectable levels in all electrically treated
      hearts. Thus, electroporation promotes uptake of PI and DNA in cardiac tissue,
      suggesting further application of this method for therapeutic genes.

PMID- 9755848
TI  - Rat liver mitochondria can hydrolyse thiamine pyrophosphate to thiamine
      monophosphate which can cross the mitochondrial membrane in a carrier-mediated
      process.
AB  - We show here that TPP --> TMP conversion can take place in rat liver
      mitochondria. This occurs via the novel, putative TPP pyrophosphatase localised
      in the mitochondrial matrix, as shown both by digitonin titration and by an HPLC
      enzyme assay carried out on the mitochondrial matrix fraction. Certain features
      of the reaction, including the substrate and pH dependence, are reported.
      Additional evidence is given that externally added TMP can cross the
      mitochondrial membrane in a manner consistent with the occurrence of a carrier
      mediated process. This can occur both via the TPP translocator and via a novel
      translocator, inhibited by CAT but different from the ADP/ATP carrier.

PMID- 9755850
TI  - Thimet oligopeptidase: site-directed mutagenesis disproves previous assumptions
      about the nature of the catalytic site.
AB  - Zinc metallopeptidases that contain the His-Glu-Xaa-Xaa-His (HEXXH) motif
      generally have a third ligand of the metal ion that may be either a Glu residue
      (in clan MA) or a His residue (in clan MB) (Rawlings and Barrett (1995) Methods
      Enzymol. 248, 183-228). Thimet oligopeptidase has not yet been assigned to either
      clan, and both Glu and His residues have been proposed as the third ligand. We
      mutated candidate ligand residues in the recombinant enzyme and identified Glu,
      His and Asp residues that are important for catalytic activity and/or stability
      of the protein. However, neither of the Glu and His residues close to the HEXXH
      motif that have previously been suggested to be ligands is required for the
      binding of zinc. We conclude that thimet oligopeptidase is not a member of clan
      MA or clan MB and it is likely that the enzyme possesses a catalytic site and
      protein fold different from those identified in any metallopeptidase to date. The
      definitive identification of the third zinc ligand may well require the
      determination of the crystallographic structure of thimet oligopeptidase or one
      of its homologues.

PMID- 9755849
TI  - Molecular cloning and characterization of RBCK2, a splicing variant of a RBCC
      family protein, RBCK1.
AB  - RBCK1 (RBCC protein interacting with PKC 1) has two coiled-coil regions, a RING
      finger, a B-box and a B-box-like motif. RBCK2, a cDNA fragment related to RBCK1
      was obtained, that lacks the 161-bp sequence of RBCK1 and encodes 260 amino acid
      residues. The 240-amino acid sequence in the NH2-terminal of RBCK2 is identical
      with RBCK1 and contains two coiled-coil regions but no other structural motifs,
      whereas the 20-amino acid sequence in the COOH-terminal is distinct from RBCK1.
      The analysis of genomic DNA revealed that RBCK1 and RBCK2 are generated from a
      single gene by alternative splicing. The RBCK1 protein interacted with the RBCK1
      and RBCK2 proteins, but the RBCK2 protein did not interact with itself, in vitro.
      The RBCK2 protein fused with the DNA-binding domain of yeast GAL4 (GAL4DBD) did
      not show a transcriptional activity, but the RBCK2 protein inhibited the
      transcriptional activity of the RBCK1 protein fused with GAL4DBD. These results
      suggest that RBCK2 may inhibit the transcriptional activity of RBCK1 probably
      through complex formation with RBCK1.

PMID- 9755851
TI  - Anisoosmotic regulation of the Mi-2 autoantigen mRNA in H4IIE rat hepatoma cells
      and primary hepatocytes.
AB  - Using the differential display polymerase chain reaction (DDRT-PCR) a 169 bp cDNA
      product, which is 88.8% homologous to the human Mi-2beta autoantigen, was
      identified in H4IIE rat hepatoma cells. At protein level 100% homology was found.
      The Mi-2 mRNA was downregulated after hypoosmotic exposure and upregulated after
      hyperosmotic exposure in H4IIE cells and rat hepatocytes. The human Mi-2 is an
      autoantigen in dermatomyositis and is a member of the SNF/RAD 54 helicase family.
      Accordingly, Mi-2 may not only be a target of osmosignalling but could also be
      involved in the osmosignalling pathway towards gene expression in H4IIE and liver
      parenchymal cells.

PMID- 9755852
TI  - Glucocorticoids decrease cytochrome c oxidase activity of isolated rat kidney
      mitochondria.
AB  - The importance of mitochondria is rising as a target in pathologic processes such
      as ischemia. We have investigated the effects of hydrocortisone, prednisolone,
      dexamethasone and triamcinolone on oxidative phosphorylation, Ca2+ fluxes,
      swelling and membrane potentials in isolated kidney mitochondria. The measurement
      of respiration state 3 showed a significant decrease in presence of
      glucocorticoids whereas the other respiration states were not modified. When
      mitochondria were uncoupled and either the complexes III and IV or the complex IV
      were stimulated, the O2 consumption was decreased by glucocorticoids. These
      results suggest the cytochrome c oxidase is a target of the glucocorticoid effect
      on the respiratory chain. Indeed, the other mitochondrial functions investigated
      were unchanged, ruling out a direct effect on Ca2+ fluxes or swelling. A
      regulation of cytochrome c oxidase activity by glucocorticoids will be of
      particular interest in pathology involving metabolic insult.

PMID- 9755853
TI  - Synergistic upregulation of metalloproteinase-9 by growth factors and
      inflammatory cytokines: an absolute requirement for transcription factor NF-kappa
      B.
AB  - Matrix metalloproteinase (MMPs) enzymes are implicated in matrix remodelling
      during proliferative inflammatory processes including wound healing. We report
      here synergistic upregulation of MMP-9 protein and mRNA by platelet-derived
      growth factor (PDGF) or basic fibroblast growth factor (bFGF) in combination with
      interleukin-1alpha (IL-1alpha) or tumour necrosis factor-alpha (TNF-alpha) in
      primary rabbit and human dermal fibroblasts. The synergistic interaction between
      growth factors and cytokines implies that basement membrane remodelling is
      maximal physiologically when both are present together. The signalling pathways
      mediating this synergistic regulation are not understood, although analysis of
      the MMP-9 promoter has identified an essential proximal AP-1 element and an
      upstream nuclear factor kappa-B (NF-kappaB) site. Using electromobility shift
      assays, binding to the AP-1 site was only slightly increased by growth factors
      and cytokines. NF-kappaB binding was rapidly induced by IL-1alpha or TNF-alpha
      but was neither induced nor potentiated by bFGF or PDGF. Neither AP-1 nor NF
      kappaB was therefore sufficient on its own for synergistic regulation. Using a
      recently developed adenovirus that overexpresses the inhibitory subunit, IkappaB
      alpha, we demonstrated an absolute requirement for NF-kappaB in upregulation of
      MMP-9. Activation of NF-kappaB binding by inflammatory cytokines was therefore
      necessary but not sufficient for synergistic upregulation of MMP-9.

PMID- 9755854
TI  - Potentiation of nitric oxide synthase expression by superoxide in interleukin 1
      beta-stimulated rat mesangial cells.
AB  - Exposure of mesangial cells to superoxide, generated by the hypoxanthine/xanthine
      oxidase system or by the redox cycler 2,3-dimethoxy-1,4-naphthoquinone caused a
      concentration-dependent amplification of interleukin (IL)-1beta-stimulated
      nitrite production. The effect of superoxide was accompanied by an increase in
      inducible nitric oxide synthase (iNOS) protein and iNOS mRNA levels. Incubation
      of mesangial cells with superoxide alone did not induce iNOS expression. To
      elucidate whether the increase of iNOS expression is due to transcriptional
      upregulation we fused a 4.5-kb genomic iNOS fragment that contains the
      transcriptional start site of the rat iNOS gene to a luciferase reporter gene. In
      transient transfection studies, superoxide caused a 10-fold augmentation of iNOS
      promoter activity in IL-1beta-challenged mesangial cells. Our data identify
      superoxide as a co-stimulatory factor amplifying cytokine-induced iNOS gene
      expression and subsequent nitric oxide (NO) synthesis.

PMID- 9755855
TI  - TNF-alpha converting enzyme (TACE) is inhibited by TIMP-3.
AB  - TNF-alpha converting enzyme (TACE; ADAM-17) is a membrane-bound disintegrin
      metalloproteinase that processes the membrane-associated cytokine proTNF-alpha to
      a soluble form. Because of its putative involvement in inflammatory diseases,
      TACE represents a significant target for the design of specific synthetic
      inhibitors as therapeutic agents. In order to study its inhibition by tissue
      inhibitors of metalloproteinases (TIMPs) and synthetic inhibitors of
      metalloproteinases, the catalytic domain of mouse TACE (rTACE) was overexpressed
      as a soluble Ig fusion protein from NS0 cells. rTACE was found to be well
      inhibited by peptide hydroxamate inhibitors as well as by TIMP-3 but not by TIMP
      1, -2 and -4. These results suggest that TIMP-3, unlike the other TIMPs, may be
      important in the modulation of pathological events in which TNF-alpha secretion
      is involved.

PMID- 9755856
TI  - Cleavage and activation of proteinase-activated receptor-2 on human neutrophils
      by gingipain-R from Porphyromonas gingivalis.
AB  - Gingipain-R, the major arginine-specific proteinase from Porphyromonas
      gingivalis, a causative agent of adult periodontal disease, was found to cleave a
      model peptide representing the cleavage site of proteinase-activated receptor-2
      (PAR-2), a G-protein-coupled receptor found on the surface of neutrophils. The
      bacterial proteinase was also shown to induce an increase in the intracellular
      calcium concentration of enzyme-treated neutrophils, most probably due to PAR-2
      activation. This response by neutrophils to gingipain-R may be a mechanism for
      the development of inflammation associated with periodontal disease.

PMID- 9755857
TI  - Isolation and characterization of the Candida albicans gene for mRNA 5'
      triphosphatase: association of mRNA 5'-triphosphatase and mRNA 5'
      guanylyltransferase activities is essential for the function of mRNA 5'-capping
      enzyme in vivo.
AB  - The amino acid sequence of the Saccharomyces cerevisiae mRNA 5'-triphosphatase
      (TPase) diverges from those of higher eukaryotes. In order to confirm the
      sequence divergence of TPases in lower and higher eukaryotes, the Candida
      albicans gene for TPase was identified and characterized. This gene designated
      CaCET1 (C. albicans mRNA 5'-capping enzyme triphosphatase 1) has an open reading
      frame of 1.5 kb, which can encode a 59-kDa protein. Although the N-terminal one
      fifth of S. cerevisiae TPase (ScCet1p) is missing in CaCet1p, CaCet1p shares
      significant sequence similarity with ScCet1p over the entire region of the
      protein; the recombinant CaCet1p, which was expressed as a fusion protein with
      glutathione S-transferase (GST), displayed TPase activity in vitro. CaCET1
      rescued CET1-deficient S. cerevisiae cells when expressed under the control of
      the ADH1 promoter, whereas the human capping enzyme derivatives that are active
      for TPase activity but defective in mRNA 5'-guanylyltransferase (GTase) activity
      did not. Yeast two-hybrid analysis revealed that C. albicans Cet1p can bind to
      the S. cerevisiae GTase in addition to its own partner, the C. albicans GTase. In
      contrast, neither the full-length human capping enzyme nor its TPase domain
      interacted with the yeast GTase. These results indicate that the failure of the
      human TPase activity to complement an S. cerevisiae cet1delta null mutation is
      attributable, at least in part, to the inability of the human capping enzyme to
      associate with the yeast GTase, and that the physical association of GTase and
      TPase is essential for the function of the capping enzyme in vivo.

PMID- 9755858
TI  - SKAP-HOM, a novel adaptor protein homologous to the FYN-associated protein
      SKAP55.
AB  - A recombinant GST-Fyn-SH2 domain was used to purify proteins from lysates of
      pervanadate treated EL4 cells. N-terminal sequencing and molecular cloning of one
      of the purified polypeptides resulted in the identification of a novel adaptor
      protein that shares strong structural homology to the recently cloned Fyn
      associated adaptor protein SKAP55. This protein was termed SKAP-HOM (SKAP55
      homologue). Despite their striking homology, SKAP55 and SKAP-HOM have distinct
      characteristics. Thus, unlike SKAP55, which is exclusively expressed in T
      lymphocytes, SKAP-HOM expression is ubiquitous. Furthermore, while SKAP55 is
      constitutively tyrosine phosphorylated in resting human T cells, SKAP-HOM is
      expressed as a non-phosphorylated protein in the absence of external stimulus but
      becomes phosphorylated following T cell activation. In addition, SKAP-HOM does
      not associate with p59fyn in T cells although it represents a specific substrate
      for the kinase in COS cells. Finally, we demonstrate that, as previously shown
      for SKAP55, SKAP-HOM interacts with the recently identified polypeptide SLAP-130.

PMID- 9755859
TI  - Type A botulinum neurotoxin proteolytic activity: development of competitive
      inhibitors and implications for substrate specificity at the S1' binding subsite.
AB  - Type A botulinum neurotoxin (botox A) is a zinc metalloprotease that cleaves only
      one peptide bond in the synaptosomal protein, SNAP-25. Single-residue changes in
      a 17-residue substrate peptide were used to develop the first specific,
      competitive inhibitors of its proteolytic activity. Substrate analog peptides
      with P4, P3, P2' or P3' cysteine were readily hydrolyzed by the toxin, but those
      with P1 or P2 cysteine were not cleaved and were inhibitors. Peptides with either
      D- or L-cysteine as the N-terminus, followed by the last six residues of the
      substrate, were the most effective inhibitors, each with a Ki value of 2 microM.
      Elimination of the cysteine sulfhydryl group yielded much less effective
      inhibitors, suggesting that inhibition was primarily due to binding of the active
      site zinc by the sulfhydryl group. Botox A displayed an unusual requirement for
      arginine as the P1' inhibitor residue, demonstrating that the S1' binding subsite
      of botox A is dissimilar to those of most other zinc metalloproteases. This
      characteristic is an important element in shaping the substrate specificity of
      botox A.

PMID- 9755860
TI  - Identification and differential regional expression of KOR-3/ORL-1 gene splice
      variants in mouse brain.
AB  - KOR-3, also known as ORL-1, is a member of the opioid receptor family, encoding
      the murine receptor for orphanin FQ/nociceptin. In the current studies we have
      identified five different splice variants of KOR-3 in mouse brain, three of which
      have not been previously reported. In addition to variants with a 15 bp deletion
      at the 3'-end of the first coding exon (KOR-3d) and an 81 bp insertion between
      the second and third coding exons (KOR-3e), three new variants with insertions of
      34 (KOR-3a), 98 (KOR-3b), and 139 bp (KOR-3c) between the first and second coding
      exons have been obtained. The expression of the three variants in mouse brain
      varies markedly among brain regions with a distribution which is quite distinct
      from KOR-3 itself. Of greatest interest was the presence of high levels of KOR-3a
      in the striatum, a region with no demonstrable KOR-3, and in the cortex. KOR-3c
      was seen in the periaqueductal gray and hypothalamus, regions where KOR-3
      predominated. The brainstem had similar levels of KOR-3, KOR-3a, and KOR-3d. In
      contrast, KOR-3d was most prominent in the cerebellum. KOR-3b levels were very
      low throughout.

PMID- 9755861
TI  - Probing pore topology and conformational changes of Kir2.1 potassium channels by
      cysteine scanning mutagenesis.
AB  - Using cysteine (Cys) scanning mutagenesis of the inward rectifier K+ channel
      Kir2.1, we investigated its pore structure and putative conformational changes.
      In the background of the Kir2.1 mutant C149F which showed no sensitivity towards
      Cys-modifying reagents, Cys residues were introduced at 10 positions in the H5
      pore region. Out of six functional mutants, T141C and F147C showed clear changes
      in current amplitude when Cys-modifying reagents were applied from the external
      side. These results suggest that the corresponding sections of the H5 pore region
      face to the external side which is in contrast to the results previously obtained
      for voltage-gated K+ (Kv) channels. Using the mutants T141C and F147C, we
      investigated whether or not Kir2.1 channels show state-dependent conformational
      changes of the pore structure. Substantial alterations of the holding potential
      or external K+ concentration, however, did not cause any significant change in
      the speed of channel modification upon application of Cys-specific reagents,
      suggesting that Kir2.1 channels do not undergo conformational changes, in
      contrast to C-type inactivating Kv channels.

PMID- 9755862
TI  - Following G-quartet formation by UV-spectroscopy.
AB  - Oligodeoxynucleotides which include stretches of guanines form a well-known
      tetrameric structure. We show that the recording of reversible absorbance changes
      at 295 nm allows to precisely monitor intramolecular guanine (G)-quartet
      formation and dissociation. Accurate Tm and thermodynamic values could be easily
      extracted from the data, whereas classical recordings at 260 nm led to a much
      larger uncertainty and in extreme cases, to completely inaccurate measurements.
      This inverted denaturation profile was observed for all G-quartet-forming
      oligonucleotides studied so far. This technique is very useful in all cases where
      intramolecular or intermolecular quadruplex formation is suspected.

PMID- 9755863
TI  - Poliovirus 2A proteinase cleaves directly the eIF-4G subunit of eIF-4F complex.
AB  - The initiation of translation on eukaryotic mRNA is governed by the concerted
      action of polypeptides of the eIF-4F complex. One of these polypeptides, eIF-4G,
      is proteolytically inactivated upon infection with several members of the
      Picornaviridae family. This cleavage occurs by the action of virus-encoded
      proteinases: 2Apro (entero- and rhinovirus) or Lpro (aphthovirus). An indirect
      mode of eIF-4G cleavage through the activation of a second cellular proteinase
      has been proposed in the case of poliovirus. Although cleavage of eIF4G by rhino-
      and coxsackievirus 2Apro has been achieved directly in vitro, a similar activity
      has not been documented to date for poliovirus 2Apro. We report here that a
      recombinant form of poliovirus 2Apro fused to maltose binding protein (MBP)
      directly cleaves human eIF-4G from a highly purified eIF-4F complex. Efficient
      cleavage of eIF-4G requires magnesium ions. The presence of other initiation
      factors such as eIF-3, eIF-4A or eIF-4B mimics in part the stimulatory effect of
      magnesium ions and probably stabilizes the cleavage products of eIF-4G generated
      by 2Apro. These results suggest that efficient cleavage of eIF4G by MBP-2Apro
      requires a proper conformation of this factor. Finally, MBP-2Apro protein cleaves
      an eIF-4G-derived synthetic peptide at the same site as rhino- and coxsackievirus
      2Apro (R485-G486).

PMID- 9755864
TI  - The 26-mer peptide released from SNAP-25 cleavage by botulinum neurotoxin E
      inhibits vesicle docking.
AB  - Botulinum neurotoxin E (BoNT E) cleaves SNAP-25 at the C-terminal domain
      releasing a 26-mer peptide. This peptide product may act as an excitation
      secretion uncoupling peptide (ESUP) to inhibit vesicle fusion and thus contribute
      to the efficacy of BoNT E in disabling neurosecretion. We have addressed this
      question using a synthetic 26-mer peptide which mimics the amino acid sequence of
      the naturally released peptide, and is hereafter denoted as ESUP E. This
      synthetic peptide is a potent inhibitor of Ca2+-evoked exocytosis in
      permeabilized chromaffin cells and reduces neurotransmitter release from
      identified cholinergic synapses in in vitro buccal ganglia of Aplysia
      californica. In chromaffin cells, both ESUP E and BoNT E abrogate the slow
      component of secretion without affecting the fast, Ca2+-mediated fusion event.
      Analysis of immunoprecipitates of the synaptic ternary complex involving SNAP-25,
      VAMP and syntaxin demonstrates that ESUP E interferes with the assembly of the
      docking complex. Thus, the efficacy of BoNTs as inhibitors of neurosecretion may
      arise from the synergistic action of cleaving the substrate and releasing peptide
      products that disable the fusion process by blocking specific steps of the
      exocytotic cascade.

PMID- 9755865
TI  - Gos1p, a Saccharomyces cerevisiae SNARE protein involved in Golgi transport.
AB  - Specific transport between secretory compartments requires that vesicular
      carriers contain targeting proteins known as SNAREs. Ten v-SNAREs have been
      identified in the genome of the yeast Saccharomyces cerevisiae by sequence
      analysis. We report here the characterization of Gos1p, a v-SNARE localized to
      the Golgi compartment and likely homolog of the mammalian protein GOS-28/GS28.
      Gos1p is a type II membrane protein with characteristic SNARE sequence hallmarks
      and is functionally a SNARE protein. Gos1p was originally identified as a 28 kDa
      protein in an immunoprecipitate of the cis-Golgi t-SNARE Sed5p. This interaction
      between Sed5p and Gos1p is direct as demonstrated by in vitro binding with
      recombinant proteins. Deletion of GOS1 results in viable haploids with modest
      growth and secretory defects. Close examination of the secretory phenotype of
      GOS1-disrupted cells suggests that Gos1p may play a role in multiple transport
      steps, specifically ER-Golgi and/or intra-Golgi transport.

PMID- 9755867
TI  - Truncated recombinant light harvesting complex II proteins are substrates for a
      protein kinase associated with photosystem II core complexes.
AB  - Previous studies directed towards understanding phosphorylation of the
      chlorophyll alb binding proteins comprising light harvesting complex II (LHC II)
      have concentrated on a single phosphorylation site located close to the N
      terminus of the mature proteins. Here we show that a series of recombinant pea
      Lhcb1 proteins, each missing an N-terminal segment including this site, are
      nevertheless phosphorylated by a protein kinase associated with a photosystem II
      core complex preparation. An Lhch1 protein missing the first 58 amino acid
      residues is not, however, phosphorylated. The results demonstrate that the LHC II
      proteins are phosphorylated at one or more sites, the implications of which are
      discussed.

PMID- 9755866
TI  - Agonist stimulation of B1 and B2 kinin receptors causes activation of the MAP
      kinase signaling pathway, resulting in the translocation of AP-1 in HEK 293
      cells.
AB  - In response to bradykinin, phosphorylated MAP kinases (ERK-1 and ERK-2) were
      abundantly increased in HEK 293 cells, which overexpress the rat B2 kinin
      receptor. In a similar way des-Arg9-bradykinin stimulation of B1 kinin receptor
      overexpressing HEK 293 cells caused activation of the same species of MAP kinase.
      Furthermore, nuclear translocation of transcription factor AP-1 was also found in
      the cells after stimulation with either agonist. PD98059, a MAP kinase kinase
      (MEK-1) inhibitor, blocked the agonist-induced AP-1 translocation as well as the
      phosphorylation of the MAP kinases. This communication provides the first
      evidence for both B1 and B2 kinin receptors mediating the MAP kinase signaling
      pathway to activate AP-1.

PMID- 9755868
TI  - Phosphorylation of the translational regulator, PHAS-I, by protein kinase CK2.
AB  - The primary site in PHAS-I for phosphorylation by protein kinase CK2 in vitro was
      identified as Ser111. A relatively small amount of phosphorylation of Ser99 was
      also detected, and mutating Ser99 to Ala in PHAS-I slightly decreased
      phosphorylation by CK2 in vitro. In contrast, mutating Ser111 to Ala almost
      abolished phosphorylation, confirming Ser111 as the preferred site for CK2.
      Phosphorylation of Ser111 did not decrease binding of PHAS-I to eIF4E, and
      results of peptide mapping experiments with PHAS-I immunoprecipitated from 32P
      labeled adipocytes indicated that Ser111 was not phosphorylated in cells. These
      results support the conclusion that CK2 is not involved in the control of PHAS-I.

PMID- 9755869
TI  - Site-specific regulatory interaction between spinach leaf sucrose-phosphate
      synthase and 14-3-3 proteins.
AB  - We report an Mg2+-dependent interaction between spinach leaf sucrose-phosphate
      synthase (SPS) and endogenous 14-3-3 proteins, as evidenced by co-elution during
      gel filtration and co-immunoprecipitation. The content of 14-3-3s associated with
      an SPS immunoprecipitate was inversely related to activity, and was specifically
      reduced when tissue was pretreated with 5-aminoimidazole-4-carboxamide riboside,
      suggesting metabolite control in vivo. A synthetic phosphopeptide based on Ser
      229 was shown by surface plasmon resonance to bind a recombinant plant 14-3-3,
      and addition of the phosphorylated SPS-229 peptide was found to stimulate the SPS
      activity of an SPS:14-3-3 complex. Taken together, the results suggest a
      regulatory interaction of 14-3-3 proteins with Ser-229 of SPS.

PMID- 9755870
TI  - Concomitant activation of Gi and Gq protein-coupled receptors does not require an
      increase in cytosolic calcium for platelet aggregation.
AB  - U46619 is a potent platelet agonist, its binding to the thromboxane A2 receptor
      resulting in Gq-binding protein-mediated responses; nevertheless, it is unable to
      cause platelet aggregation, unless released ADP is present. In this study we
      demonstrate that Gi activation is the step U46619 lacks to cause platelet
      aggregation; in fact, when platelets were treated with an ADP scavenger system,
      the response to U46619 was restored by the addition of epinephrine, which
      activates platelets via a Gi protein. The concomitant activation of Gi and Gq
      proteins does not require increased cytosolic calcium to cause aggregation, as
      assessed by the fact that platelets treated with the intracellular calcium
      chelator BAPTA were able to respond to U46619 provided ADP or epinephrine was
      present. Moreover, as the calcium ionophore ionomycin, at low concentrations,
      potentiated the response to U46619 but not to epinephrine, we may conclude that
      calcium influx preferentially activates a Gi downstream signalling pathway.

PMID- 9755871
TI  - The expression of epidermal growth factor and transforming growth factor-alpha
      mRNA in the small intestine of suckling rats: organ culture study.
AB  - Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha)
      are associated with regulation of various gastrointestinal functions. In order to
      better understand their role in developing small intestine EGF, TGF-alpha and EGF
      R steady-state mRNA levels and transcript stability were determined. Reverse
      transcription (RT) competitive-polymerase chain reaction (PCR) revealed that
      intestinal TGF-alpha mRNA levels were 10-fold higher in comparison with EGF mRNA.
      The primary intestinal culture technique was used to evaluate mRNA stability. The
      stability of TGF-alpha mRNA was remarkably lower than the stability of EGF mRNA.
      High levels of TGF-alpha mRNA accompanied by high degradation rate of this mRNA
      suggested a rapid turnover of intestinal TGF-alpha mRNA.

PMID- 9755872
TI  - Dephosphorylation of perilipin by protein phosphatases present in rat adipocytes.
AB  - By incubating 32P-labelled adipocytes, and extracts from these cells, in the
      presence or absence of specific inhibitors, we evaluated the contribution of
      protein phosphatases PP1, PP2A and PP2C, to the dephosphorylation of perilipin,
      an acutely hormone-regulated adipocyte phosphoprotein. Under conditions to
      completely inhibit PP2A activity, perilipin phosphatase activity in extracts
      remain unaffected, but PP1 inhibition results in abolition of perilipin
      phosphatase activity. Inhibition of PP1 (and 2A) in intact adipocytes stimulated
      lipolysis and increased phosphorylation of perilipin. No involvement of PP2C was
      found. Hence, PP1 constitutes the predominant if not sole perilipin phosphatase
      in adipocytes.

PMID- 9755873
TI  - Immunopotentiation with low-dose cyclophosphamide in the active specific
      immunotherapy of cancer.
AB  - This paper reviews the use of low-dose cyclophosphamide (CY) with active specific
      immunotherapy in patients with advanced melanoma and other metastatic cancers,
      and outlines the basic scientific research that supports this use. In various
      animal models, CY augments delayed-type hypersensitivity responses, increases
      antibody production, abrogates tolerance, and potentiates antitumor immunity. The
      mechanism of CY immunopotentiation involves inhibition of a suppressor function,
      as indicated by extensive work in the MOPC-315 plasmacytoma murine model. Human
      studies of the immunopotentiating effect of CY have yielded both positive and
      negative results. Toxicity associated with low-dose CY has been mild in these
      studies. Results of efficacy have been variable for reasons such as small sample
      sizes, short follow-up periods, and the weaker immunogenicity of human tumor
      associated antigens. Although beneficial clinical outcomes have been observed in
      historically controlled trials, there are few randomized, controlled trials that
      evaluate outcome in relation to CY immunopotentiation of active specific
      immunotherapy. Additional randomized, controlled trials should be done to examine
      the clinical efficacy of CY immunopotentiation of therapeutic cancer vaccines.

PMID- 9755874
TI  - Induction of anti-idiotypic humoral and cellular immune responses by a murine
      monoclonal antibody recognizing the ovarian carcinoma antigen CA125 encapsulated
      in biodegradable microspheres.
AB  - The use of biodegradable poly(DL-lactic-co-glycolic acid) microspheres as a
      cancer vaccine delivery system for induction of anti-idiotypic responses was
      investigated using a murine monoclonal antibody B43.13 that recognizes the human
      ovarian cancer antigen CA125. Immunization of mice with mAb B43.13 encapsulated
      in poly(DL-lactic-co-glycolic acid) microspheres resulted in enhanced humoral and
      cellular immune responses compared with mAb B43.13 alone or mAb B43.13 mixed with
      microspheres. The antibody responses could be further enhanced by the co
      encapsulation of mAb B43.13 with monophosphoryl lipid A, a non-toxic adjuvant, in
      microspheres. Anti-idiotypic humoral responses were shown to result in Ab2
      antibodies mimicking the nominal antigen CA125 and Ab3 antibodies recognizing
      CA125. Further, microsphere delivery of mAb B43.13 also resulted in induction of
      T cell responses involving T2 cells reactive with mAb B43.13 epitopes and T3
      cells recognizing CA125. These results indicate that microsphere delivery of Abl
      can induce both humoral and cellular anti-idiotypic responses relevant to cancer
      antigens. This raises the possibility of the use of such formulations for anti
      idiotypic induction immunotherapy for cancer.

PMID- 9755875
TI  - Induction of HLA-unrestricted and HLA-class-II-restricted cytotoxic T lymphocytes
      against MUC-1 from patients with colorectal carcinomas using recombinant MUC-1
      vaccinia virus.
AB  - We recently reported that immunization with a recombinant MUC-1 vaccinia virus
      (rVMUC-1) protected C57BL/6 mice from challenge with DF3/MUC-1-positive syngeneic
      tumors. To elucidate whether anti-MUC-1 tumor immunity, especially MUC-1-specific
      cytotoxic T lymphocytes (CTI), can be induced in cancer patients by rVMUC-1, we
      stimulated the peripheral blood lymphocytes from patients with DF3/MUC-1+ or
      DF3/MUC-1 colon carcinomas using the autologous monocytes infected with rVMUC-1
      (rVAMN). The stimulated T lymphocytes from two patients with DF3/MUC-1-positive
      colorectal carcinomas (rVPY+T and rVPW+T) demonstrated HLA-unrestricted
      cytotoxicity against MUC-1, whereas those from the patient with DF3/MUC-1
      negative colon carcinoma (rVPA-T) did not. The HLA-unrestricted cytotoxicity was
      demonstrated by the CD8+ T cells possibly recognizing an epitope present on the
      tandem repeats. Adoptive immunotherapy who performed three times with patient PY,
      at 4-week intervals. The adoptive transfer of the first stimulated lymphocytes,
      demonstrating a high level of HLA-unrestricted cytotoxicity against MUC-1,
      resulted in the significant reduction of the liver metastasis of patient PY.
      However, HLA-unrestricted cytotoxicity against MUC-1 was extremely reduced at the
      second transfer and finally eliminated at the third, whereas the CD4+ T cells
      demonstrating HLA-class-II-restricted cytotoxicity against MUC-1 predominantly
      proliferated at the third adoptive immunotherapy treatment. The liver metastasis
      and the serum levels of tumor markers (carcinoembryonic antigen CA19-9)
      demonstrated a rapid and marked increment after the second transfer and
      especially after the third. These results suggest that the HLA-unrestricted
      cytotoxic CD8+ T cells against MUC-1, induced in patients with DF3/MUC-1+
      colorectal carcinomas using rVMUC-1, correlate with the antitumor activity in
      vivo.

PMID- 9755876
TI  - Tumour-specific MHC-class-II-restricted responses after in vitro sensitization to
      synthetic peptides corresponding to gp100 and Annexin II eluted from melanoma
      cells.
AB  - In a search for potentially tumour-specific MHC-class-II-restricted antigens, the
      immunogenicity of endogenous peptides that had been eluted from HLA-DR molecules
      of the human melanoma cell line FM3 (HLA-DRB1*02x, DRB1*0401) was tested in
      vitro. Two 16-mers representing gp100 positions 44-59, and annexin II positions
      208-223 bound well to isolated DRB1*0401 molecules and are discussed here. HLA-DR
      matched normal donors' T cells were cultured with peptide-pulsed artificial
      antigen-presenting cells (CHO cells cotransfected with genes for HLA-DRB1*0401
      and CD80 and coexpressing high levels of both human molecules). Specific
      sensitization was achieved against both peptides, as measured in assays of
      autocrine proliferation and interleukin-2 secretion. Moreover, responses to
      native autologous melanoma cells but not to autologous B cells were also
      observed. In view of the expression of fas by the activated T cells and of fas
      ligand by the melanoma cells, blockade of potential fas/ fas-ligand interactions
      was undertaken using monoclonal antibodies (mAb). The antagonistic fas-specific
      mAb M3, but not the fas agonist M33, caused a markedly enhanced T cell response
      to FM3 cells. These results demonstrate that synthetic peptide antigens are able
      to sensitize T cells in vitro for effective MHC-class-II-restricted recognition
      of melanoma cells.

PMID- 9755877
TI  - Biodistribution of 111In-labelled engineered human antibody CTM01 (hCTM01) in
      ovarian cancer patients: influence of prior administration of unlabelled hCTM01.
AB  - mAb hCTM01 binds a carcinoma-associated antigen, the MUC1 gene product. The
      antigen is also present in the circulation, and administration of 111In-labelled
      hCTM01 results in the formation of immune complexes with enhanced accumulation in
      the liver. To avoid the unwanted effect of circulating radioactive immune
      complexes, a strategy to remove the circulating antigen was investigated using a
      split-dosage schedule. Eleven patients suspected of having ovarian carcinoma were
      injected with 1 mg/kg unlabelled hCTM01, 1 h before receiving 0.1 mg/kg 111In
      labelled hCTM01 (100 M Bq). The amount of radioactivity was determined in
      resected tumour tissue, various normal tissues and blood samples obtained at
      laparotomy 6 days postinjection (p.i.). In all patients, the circulating antigen
      decreased to its nadir after the unlabelled antibody infusion and immune complex
      formation was demonstrated. Uptake in tumour deposits 6 days p.i. was 11.1 times
      higher than in normal tissues (P < 0.0001) and 5.9 times higher than in blood (P
      < 0.0001). 111In activity in liver tissue was comparable to 111In uptake in
      tumour tissue, and considerably lower than previously reported in patients not
      pretreated with unlabelled antibody. The split-dosing strategy would appear to be
      advantageous for use of hCTM01 as a specific carrier for the delivery of
      cytotoxic agents to patients with ovarian cancer.

PMID- 9755878
TI  - Effect of interleukin-8 on production of tumor-associated substances and
      autocrine growth of human liver and pancreatic cancer cells.
AB  - We have previously reported that human liver cancer cell lines produce
      interleukin-8 (IL-8) at high levels. Those tumor cells appeared to express two
      kinds of IL-8 receptor on their surface. In order to analyze the role of IL-8 on
      the biological characteristics of those tumor cells, we suppressed IL-8
      production from human liver (HuH-7 and HuCC-T1) and pancreatic cancer cell lines
      (HuP-T4) by treatment with IL-8 antisense oligonucleotides. Suppression of IL-8
      production resulted not only in inhibition of cell growth, but also in an
      increase in the concentrations of some tumor-associated substances such as
      carbohydrate antigen 19-9 (CA19-9) in the medium. These data indicate that IL-8
      produced by human liver and pancreatic tumors may act as an autocrine growth
      factor and may control the production of some tumor-associated substances.
      Furthermore, surface expression of sialyl-Lewis(a), which is a ligand for ELAM-1
      on human umbilical vein endothelial cells (HUVEC), HuCC-T1 and HuP-T4 cells was
      decreased and the attachment of these tumor cells to HUVEC was inhibited by
      treatment with IL-8 antisense oligonucleotide. Since the soluble form of CA19-9
      (sialyl-Lewis(a)) was shown to inhibit the tumor cell binding to HUVEC, the
      decrease in release of CA19-9 into the medium and increase in the expression of
      sialyl-Lewis(a) on the cell surface may suggest that IL-8 production from the
      tumor cells enhances metastatic potential by augmenting the binding activity of
      the tumor cells to HUVEC. These data demonstrate that a cytokine produced by
      tumor cells may function as an autocrine growth factor and affect tumor cell
      dissemination.

PMID- 9755879
TI  - Immunization with a tumor-cell-lysate-loaded autologous-antigen-presenting-cell
      based vaccine in melanoma.
AB  - The discoveries of human melanoma-associated antigens in molecular terms have
      renewed interest in peptide- or peptide- and antigen-presenting-cell (APC)-based
      cancer vaccines. Considering the limited scope of immunization using defined
      peptides, we have studied an alternative approach of specific immunization with
      tumor-lysate-loaded autologous APC (adherent peripheral mononuclear cells
      cultured in 1000 U granulocyte/macrophage-colony-stimulating factor for 14 days)
      as a surrogate vaccine. Seventeen patients (11 with active metastatic disease)
      were intradermally immunized with the vaccine in a phased dose escalation (10(5)
      10(7) cells/injection) monthly for 4 months. Thirteen patients completed all four
      immunizations showing no toxicity (3 patients had to be taken off study because
      of progressive disease and 1 patient went off study as a result of myocardial
      infarction due to multi-vessel coronary artery disease). None has shown any
      immediate or delayed toxicity attributable to the immunization and none has shown
      any evidence of autoimmunity. One patient showed a partial regression of a
      subcutaneous nodule. Thirteen patients are alive after 4+ months to 30+ months
      (17-month median survival for the group). Nine patients showed evidence of
      delayed-type hypersensitivity at the vaccine sites. Monitoring of biological
      response in conventional natural killer or cytolytic T lymphocyte assays with pre
      and post-immune peripheral blood lymphocytes revealed no consistent differences.
      The vaccine-infiltrating lymphocytes (VIL) from nine specimens were adequately
      expanded following in vitro stimulation with the respective autologous-lysate
      loaded APC for phenotypic and functional analyses. Five of the nine ex vivo
      expanded VIL were predominantly CD8+. Evidence of an antigen-specific CD8+ T cell
      response (cytotoxicity and/or tumor necrosis factor production) was detected in
      three of the five CD8+ VIL. These observations suggest that this type of vaccine
      is feasible, that it has biological activity, and that the approach may be
      improved through additional strategic manipulations.

PMID- 9755880
TI  - Individual bioequivalence: attractive in principle, difficult in practice.

PMID- 9755881
TI  - Chitosan and its use as a pharmaceutical excipient.
AB  - Chitosan has been investigated as an excipient in the pharmaceutical industry, to
      be used in direct tablet compression, as a tablet disintegrant, for the
      production of controlled release solid dosage forms or for the improvement of
      drug dissolution. Chitosan has, compared to traditional excipients, been shown to
      have superior characteristics and especially flexibility in its use. Furthermore,
      chitosan has been used for production of controlled release implant systems for
      delivery of hormones over extended periods of time. Lately, the transmucosal
      absorption promoting characteristics of chitosan has been exploited especially
      for nasal and oral delivery of polar drugs to include peptides and proteins and
      for vaccine delivery. These properties, together with the very safe toxicity
      profile, makes chitosan an exciting and promising excipient for the
      pharmaceutical industry for present and future applications.

PMID- 9755882
TI  - Chitosan-based vector/DNA complexes for gene delivery: biophysical
      characteristics and transfection ability.
AB  - PURPOSE: Chitosan, a natural cationic polysaccharide, is a candidate non-viral
      vector for gene delivery. With the aim of developing this system, various
      biophysical characteristics of chitosan-condensed DNA complexes were measured,
      and transfections were performed. METHODS: Transmission electronic microscopy
      (TEM) visualizations, sedimentation experiments, dynamic light scattering (DLS),
      and zeta potential measurements were realized. Transfections were made by using
      the luciferase reporter gene. RESULTS: In defined conditions, plasmid DNA
      formulated with chitosan produced homogenous populations of complexes which were
      stable and had a diameter of approximately 50-100 nm. Discrete particles of
      nicely condensed DNA had a donut, rod, or even pretzel shape. Chitosan/DNA
      complexes efficiently transfected HeLa cells, independently of the presence of
      10% serum, and did not require an added endosomolytic agent. In addition, gene
      expression gradually increased over time. from 24 to 96 hours, whereas in the
      same conditions the efficacy of polyethylenimine-mediated transfection dropped by
      two orders of magnitude. At 96 hours, chitosan was found to be 10 times more
      efficient than PEI. However, chitosan-mediated transfection depended on the cell
      type. This dependency is discussed here. CONCLUSIONS: Chitosan presents some
      characteristics favorable for gene delivery, such as the ability to condense DNA
      and form small discrete particles in defined conditions.

PMID- 9755883
TI  - Target specific optimization of cationic lipid-based systems for pulmonary gene
      therapy.
AB  - PURPOSE: Cationic lipids are capable of transferring foreign genes to the
      pulmonary epithelium in vivo. It is becoming increasingly clear that factors
      other than lipid molecular structure also influence efficiency of delivery using
      cationic lipid systems. This study is aimed at evaluating the effect of
      formulation variables such as cationic lipid structure, cationic lipid/DNA ratio,
      particle size, co-lipid content and plasmid topology on transgene expression in
      the lung. METHODS: The effect of varying the surface and colloidal properties of
      cationic lipid-based gene delivery systems was assessed by intratracheal
      instillation into rats. An expression plasmid encoding chloramphenicol acetyl
      transferase (CAT) was used to measure transgene expression. RESULTS: Cationic
      lipid structure, cationic lipid/DNA ratio, particle size, co-lipid content and
      topology of the plasmid, were found to significantly affect transgene expression.
      Complexation with lipids was found to have a protective effect on DNA integrity
      in bronchoalveolar lavage fluid (BALF). DNA complexed with lipid showed enhanced
      persistence in rat lungs as measured by quantitative polymerase chain reaction.
      CONCLUSIONS: Fluorescence microscopy analysis indicated that the instilled
      formulation reaches the lower airways and alveolar region. Data also suggests
      cationic lipid-mediated gene expression is primarily localized in the lung
      parenchyma and not infiltrating cells isolated from the BALF.

PMID- 9755884
TI  - Beta cyclodextrins enhance adenoviral-mediated gene delivery to the intestine.
AB  - PURPOSE: In general, the intestinal epithelium is quite refractory to viral and
      non-viral methods of gene transfer. In this report, various cyclodextrin
      formulations were tested for their ability to enhance adenoviral transduction
      efficiency in two models of the intestinal epithelium: differentiated Caco-2
      cells and rat jejunum. METHODS: Transduction efficiency of replication-deficient
      adenovirus type 5 vectors encoded with either the E. coli beta-galactosidase or
      the jellyfish green fluorescent protein gene was assessed by X-gal staining or
      visualization of fluorescence 48 hours after infection. In vivo experiments were
      performed using an intestinal loop ligation technique. RESULTS: Several
      formulations of neutral and positively charged beta cyclodextrins significantly
      enhanced adenoviral-mediated gene transfer in the selected models. The
      cyclodextrin formulations studied increased adenoviral transduction in the
      intestine by enhancing both viral binding and internalization. Viral binding was
      significantly increased on cell membranes treated with positively charged
      cyclodextrins, as seen with confocal microscopy and rhodamine-labeled virus.
      Permeability studies and TEER readings revealed that the most successful
      formulations gently disrupt cell membranes. This enhances internalization of
      viral particles and results in increased levels of gene expression. CONCLUSIONS:
      These formulations can be of value in gene transfer to cells and tissues in which
      adenoviral infection is limited due to a lack of fiber and alpha(v) integrin
      receptors. They are simple to prepare and do not affect the ability of the virus
      to transduce target cells.

PMID- 9755886
TI  - Liposomes dispersed within a thermosensitive gel: a new dosage form for ocular
      delivery of oligonucleotides.
AB  - PURPOSE: The main goal of this study was to develop an ocular controlled release
      formulation of a model oligonucleotide (pdT16), contained within liposomes
      dispersed within a thermosensitive gel composed by poloxamer 407. METHODS: The
      influence of the poloxamer concentration 2% or 27% on the stability of the
      liposomes (PC: CHOL and PC: CHOL: PEG-DSPE) was investigated. The in vitro
      release profiles of pdT16 from various poloxamer formulations (free pdT16
      dispersed within 20% and 27% poloxamer gels, pdT16 encapsulated within liposomes
      dispersed within 20% and 27% poloxamer gels) were realized using a membrane-free
      release model. RESULTS: The dispersion of liposomes within a dilute 2% poloxamer
      solution resulted in a great leakage of pdT16 from liposomes. However, the
      destabilization effect of poloxamer was reduced when higher concentration (27%)
      was used. Poloxamer dissolution was found to control the release process of
      pdT16, whereas the dispersion of liposomes within 27% poloxamer gel was shown to
      slow down the diffusion of pdT16 out from the gel. CONCLUSIONS: The dispersion of
      liposomes within a 27% poloxamer gel presented an interesting system to control
      the release of a model oligonucleotide compare to a simple gel.

PMID- 9755885
TI  - Characterization and in vivo testing of a heterogeneous cationic lipid-DNA
      formulation.
AB  - PURPOSE: To identify characteristics of lipid-DNA complexes that correlate with
      in vivo expression data. METHODS: DOTIM:cholesterol liposomes (1:1 mole ratio)
      and DNA expressing chloramphenicol acetyl transferase (CAT) were complexed at a
      4.2:1 mass ratio (cationic lipid:DNA). Complexes were fractionated by density
      gradient centrifugation. analyzed for particle size and zeta potential and
      quantitated using HPLC methods. The unfractionated complexes, "purified"
      fractions of the complexes, and purified complexes supplemented with liposomes
      were administered to mice by intravenous injection (i.v.) and intratracheal
      instillation (i.t.) and their ability to express gene product was assessed.
      RESULTS: Centrifugation separated two distinct populations within complexes one
      consisting of free liposomes and the other of lipid complexed with DNA. The
      vesicle diameter and zeta potential among separated fractions varied from 113 to
      354 nm. and + 24 to + 34 mV respectively. Re-centrifugation of the 'purified'
      fractions containing the lipid-DNA population produced a single band. CAT
      expression in lung tissue 24 hr post-i.v. was observed with the unfractionated
      complex, but not the purified form. Some activity was 'restored' with the
      liposome-supplemented complexes. In contrast, the same series of complexes
      administered by i.t. resulted in no significant difference in lung expression
      (p=0.16 ANOVA). CONCLUSIONS: An uncomplexed liposome population exists within
      DOTIM:cholesterol-DNA complexes that influences the expression of complexes
      administered i.v. but not i.t..

PMID- 9755887
TI  - Prediction of intestinal drug absorption properties by three-dimensional
      solubility parameters.
AB  - PURPOSE: The purpose of this study was to investigate the use of solubility
      parameters for the prediction of gastrointestinal absorption sites and absorption
      durations of drugs. METHODS: Three-dimensional solubility parameters of drug
      substances were calculated using an advanced parameter set based on the group
      contribution methods of Fedors and Van Krevelen/Hoftyzer. The results of the
      calculations were illustrated via Bagley diagram and related to absorption data
      reported in the literature. RESULTS: Solubility parameters of drugs which are
      known to be absorbed over a long period in human's digestive tract were found in
      a limited area within the Bagley diagram. From the three-dimensional solubility
      parameters of these substances, a region for optimal absorption with the centre
      coordinates delta(v)=20.3 (J x cm(-3))(0.5) and delta(h)=11.3 (J x cm(-3))(0.5)
      could be derived. Drugs with absorption sites along the whole gastrointestinal
      tract were found in this area. Drugs which are preferably absorbed from upper
      parts of the intestine are located in another typical region with partial
      solubility parameters delta(h) of more than 17 (J x cm(-3))(0.5). CONCLUSIONS:
      The method which is presented in this paper appears as a simple but effective
      method to estimate the absorption behaviour of new substances in drug research
      and development.

PMID- 9755888
TI  - Overexpression of human intestinal oligopeptide transporter in mammalian cells
      via adenoviral transduction.
AB  - PURPOSE: Our goals are to establish an in vitro screening system and to evaluate
      a new approach in improving oral absorption of peptides and peptide-like drugs by
      overexpression of the human intestinal oligopeptide transporter (hPepT1). This
      study characterizes the expression of hPepT1 in human intestinal Caco-2 cells,
      rat intestinal epithelial cells (IEC-18), and human cervix epithelial cells
      (Hela) after adenoviral transduction. METHODS: A recombinant replication
      deficient adenovirus carrying the hPepT1 gene was made and used as a vector for
      the expression of hPepT1. The increase in the uptake permeability of cephalexin
      and Gly-Sar was determined. The effects of time, dose, apical pH, and substrate
      specificity were evaluated. RESULTS: A significant increase in the uptake
      permeability of Gly-Sar and cephalexin was found in all three cell lines after
      viral transduction. The increase of Gly-Sar permeability in Hela. IEC-18, and
      Caco-2 cells was 85-, 46-, and 15-fold respectively. Immunoblotting using an
      antibody against hPepT1 detected high levels of a 85-98-kDa protein in all three
      infected cell lines. Substrate permeability was dependent on time of infection,
      inward pH gradients, and multiplicity of infection (MOI). Decreased infectivity
      and lower hPepT1 expression were observed in differentiated Caco-2 cells. The
      uptake was inhibited by dipeptides and beta-lactam antibiotics but not amino
      acids. CONCLUSIONS: Adenoviral infected Hela cells displayed a pronounced level
      of hPepT1 expression with a low background and high specificity to dipeptides.
      These features make this system a useful tool for screening of potential
      substrates. The success of overexpression of hPepT1 in Caco-2 and IEC-18 cells
      may lead to a novel approach in improving oral absorption of peptides and
      peptidornimetic drugs.

PMID- 9755890
TI  - Permeability characteristics of tetragastrins across intestinal membranes using
      the Caco-2 monolayer system: comparison between acylation and application of
      protease inhibitors.
AB  - PURPOSE: Three types of acyl tetragastrin (TG), acetyl-TG (C2-TG), butyryl-TG (C4
      TG) and caproyl-TG (C6-TG) were synthesized and their in vitro intestinal
      permeability characteristics were examined using Caco-2 monolayers. METHODS: The
      disappearance of acyl-TGs from the apical side of Caco-2 monolayers was estimated
      by analyzing degradation and permeation processes in terms of clearance. RESULTS:
      The amount of native TG transported to the basolateral side was very low due to
      its large degradation clearance (CLd) on the apical side. Degradation of TG was
      reduced by chemical modification with fatty acids, which resulted in an increase
      in the transport of TG across Caco-2 monolayers. In addition, the permeation
      clearance (CLp) value of carboxyfluorescein (CF), a paracellular transport and
      undegradable marker, was increased in the presence of acyl-TGs. Furthermore, we
      investigated the effects of the protease inhibitors bacitracin and gabexate on
      the transport of TG across Caco-2 monolayers. In the presence of a low
      concentration (0.1 mM) of protease inhibitor, the CLd value of TG was reduced,
      but they did not affect its CLp value. However, a higher concentration (1.0 mM)
      of bacitracin significantly reduced TG degradation on the apical side, and
      further increased its CLp value. CONCLUSIONS: We demonstrated that acylation of
      TG made it resistant to intestinal proteases and caused it to enhance absorption
      of drugs, including itself, across Caco-2 monolayers. Further, bacitracin acted
      as both a protease inhibitor and an absorption enhancer.

PMID- 9755889
TI  - Cellular uptake mechanism of amino acid ester prodrugs in Caco-2/hPEPT1 cells
      overexpressing a human peptide transporter.
AB  - PURPOSE: This study characterized the cellular uptake mechanism and hydrolysis of
      the amino acid ester prodrugs of nucleoside antiviral drugs in the transiently
      transfected Caco-2 cells overexpressing a human intestinal peptide transporter,
      hPEPT1 (Caco-2/hPEPT1 cells). METHODS: Amino acid ester prodrugs of acyclovir and
      AZT were synthesized and their apical membrane permeability and hydrolysis were
      evaluated in Caco-2/hPEPT1 cells. The cellular uptake mechanism of prodrugs was
      investigated through the competitive inhibition study in Caco-2/hPEPT1 cells.
      RESULTS: L-Valyl ester of acyclovir (L-Val-ACV) was approximately ten fold more
      permeable across the apical membrane than acyclovir and four times more permeable
      than D-valyl ester of acyclovir (D-Val-ACV). Correspondingly, L-valyl ester of
      AZT (L- Val-AZT) exhibited three fold higher cellular uptake than AZT. Therefore,
      amino acid ester prodrugs significantly increased the cellular uptake of the
      parent drugs and exhibited the D,L-stereoselectivity. Furthermore, prodrugs were
      rapidly hydrolyzed to the parent drugs by the intracellular hydrolysis, following
      the apical membrane transport. In the inhibition studies, cephalexin and small
      dipeptides strongly inhibited the cellular uptake of L-Val-ACV while L-valine had
      no effect, indicating that the peptide transporter is primarily responsible for
      the apical membrane transport of L-Val-ACV. In addition, the cellular uptake of L
      Val-ACV was five times higher in Caco-2/hPEPT1 cells than the uptake in the
      untransfected Caco-2 cells, implying the cellular uptake of L-Val-ACV was related
      to the enhancement of the peptide transport activity in Caco-2/hPEPT1 cells.
      CONCLUSIONS: Caco-2/hPEPT1 system is an efficient in vitro model for the uptake
      study of peptidyl derivatives. Amino acid ester prodrugs significantly improved
      the cellular uptake of the parent drugs via peptide transport mechanism and were
      rapidly converted to the active parent drugs by the intracellular hydrolysis.

PMID- 9755891
TI  - Transport of proteolytic enzymes across Caco-2 cell monolayers.
AB  - PURPOSE: To investigate the mechanisms by which proteolytic enzymes, such as
      trypsin, chymotrypsin, papain, and bromelain, are able to cross the intestinal
      mucosal barrier after oral administration to man. METHODS: Filter-grown Caco-2
      cell monolayers were incubated with proteolytic enzymes and then the
      transepithelial electrical resistance (TEER) and the transport of the
      paracellular marker fluorescein were monitored. The effects of the enzymes on the
      cells were investigated by light microscopy and by biochemical assays. Transport
      of intact proteases across the cells was verified by monitoring the proteolytic
      activity and MALDI-TOF mass spectroscopic identification of undegraded trypsin.
      RESULTS: Depending on time, concentration, and side of exposure to Caco-2 cell
      monolayers, all proteases decreased the TEER and increased the transport of
      fluorescein. Some morphological and metabolic changes were observed. The effects
      were reversible, but until 24 hours after removal of the proteases. Under the
      conditions of this in-vitro model, approximately 10% of the apically applied dose
      reached the basolateral compartment as biologically active, non-degraded
      molecules. CONCLUSIONS: Proteolytic enzymes were found to exert considerable
      effects on the barrier function of Caco-2 monolayers, facilitating the transport
      of normally non-absorbable compounds. This suggests the also reported, but so far
      unexplained, systemic absorption of proteolytic enzymes after oral administration
      in vivo may occur by self-enhanced paracellular transport.

PMID- 9755892
TI  - Hydrophobicity of HIV protease inhibitors by immobilized artificial membrane
      chromatography: application and significance to drug transport.
AB  - PURPOSE: The feasibility of using hydrophobicity measurements as screens for
      intracellular availability in T-cells or intestinal permeability in Caco-2 cells
      was examined. METHODS: T-cell experiments: Cells were counted, collected, then
      incubated with drug solution at 37 degrees C. At selected time intervals, uptake
      was quenched by transferring a sample into oil, followed by rinsing, lysis of
      cells, protein precipitation and analysis by HPLC. Caco-2 cell experiments: Cells
      were grown on plastic dishes for 7-10 d, then rinsed and incubated with drug
      solution at 37 degrees C. Uptake was quenched, cells were lysed, protein
      precipitated and drug was analyzed by HPLC. IAM chromatography: Stock solutions
      were injected onto an IAM column for HPLC. Mobile phase consisted of varying
      amounts of acetonitrile in buffer (pH 7.4). The capacity factor, k'IAM, was
      calculated using citric acid to measure the void volume and was obtained by
      extrapolation to pure buffer. RESULTS: Nine HIV protease inhibitors were studied
      for uptake by CEM T-cell suspensions or Caco-2 cell monolayers. Capacity factors
      (log) between IAM and C-18 columns were positively correlated for this series.
      Caco-2 uptake rates correlated well with T-cell uptake rates when normalized by
      protein mass. Single-variable regression using IAM or C-18 columns was acceptable
      for analysis of T-cell data. Correlation coefficients between T-cell uptake and
      log k'IAM or log k'C-18 were not improved with multivariable regression.
      Correlation between Caco-2 uptake and log k'IAM was enhanced when molecular
      weight and hydrogen-bonding potential were included in multivariable regression
      analysis (from r2 of 0.39 to 0.91). Correlations obtained using log k'IAM, log
      k'C-18 or log distribution coefficient (log D) were comparable when regressed
      against Caco-2 uptake using this approach. Calculated log partition coefficient
      (ClogP) provided the poorest correlation in the multivariable analysis (r2=0.57
      for T-cell uptake and r2=0.71 for Caco-2 cell uptake). CONCLUSIONS: Uptake of HIV
      protease inhibitors by T-cell suspensions or Caco-2 cell monolayers was
      positively correlated. Uptake by T-cell suspensions was adequately described by
      hydrophobicity alone. Description of uptake by Caco-2 cell monolayers required
      multivariable regression analysis in which molecular weight and hydrogen bonding
      were included. Experimental measures of hydrophobicity (log k'IAM, log k'C-18 and
      log D) were superior to ClogP in the correlation analysis.

PMID- 9755894
TI  - Permeability of articular cartilage to matrix metalloprotease inhibitors.
AB  - PURPOSE: To develop an in vitro cartilage permeation model for cartilage
      permeability study and to evaluate the effects of molecular hydrophilicity and
      cartilage location on the permeability of articular cartilage to matrix
      metalloprotease inhibitors. METHODS: An in vitro cartilage permeation model was
      developed and utilized to determine the permeability of articular cartilage to
      the matrix metalloprotease inhibitors of different hydrophilicity. Permeability
      coefficients were obtained by measuring the steady-state flux of the inhibitor
      compounds. HPLC methods were also developed and employed for the analysis of drug
      levels in assay media. RESULTS: The relationship between permeability and
      hydrophilicity of drug molecules was examined. Results indicated that the
      permeability coefficient increased with increasing hydrophilicity of the
      molecule. Additionally, the relationship between the permeability and the
      location of the cartilage section within the animal joint was investigated. Our
      results showed that the drug molecules penetrated faster in the surface layer
      cartilage than in the deep layer cartilage. CONCLUSIONS: Increasing the
      hydrophilicity of a molecule would increase its permeability across articular
      cartilage. The in vitro cartilage permeation model developed could be used to
      rank order drug compounds according to their cartilage permeability profiles and
      to aid in drug selection and development.

PMID- 9755893
TI  - Mechanisms of liposomes/water partitioning of (p-methylbenzyl)alkylamines.
AB  - PURPOSE: The objective of this study was to compare and interpret the variations
      in lipophilicity of homologous (p-methylbenzyl)alkylamines (MBAAs) in isotropic
      (octanol/water) and anisotropic (zwitterionic liposomes/water) system. METHODS:
      Two experimental approaches were used, namely the pH-metric method to measure
      lipophilicity parameters in octanol/water and liposomes/water systems, and
      changes in NMR relaxation rates to validate the former method and to gain
      additional insights into the mechanisms of liposomes/water partitioning. RESULTS:
      For long-chain homologues (N-butyl to N-heptyl), the octanol/water and
      liposomes/water systems mostly expressed hydrophobicity. In contrast, the
      lipophilicity of the shorter homologues (N-methyl to N-propyl) in the two systems
      expressed various electrostatic and polar interactions. CONCLUSIONS: The study
      sheds light on the molecular interactions between zwitterionic liposomes and
      amphiphilic solutes in neutral and cationic form.

PMID- 9755895
TI  - Prodrugs of gestodene for matrix-type transdermal drug delivery systems.
AB  - PURPOSE: The aim of this study was to enhance the transdermal absorption of the
      highly active progestin gestodene from matrix type transdermal delivery systems
      (TDDS) by formation of prodrugs with improved matrix solubility. METHODS:
      Gestodene esters were synthesized via acylation of the drug with the respective
      carboxylic anhydrides. Subsequently TDDS were produced using the solvent cast
      method. Selected formulations were examined with in vitro diffusion experiments
      using skin of nude mice. RESULTS: One prodrug, gestodene caproate proved to be an
      oil at ambient temperature and showed a very high solubilty of over 10.5% in the
      TDDS matrix. Within in vitro penetration studies using those systems the prodrug
      exhibited a significantly higher transdermal penetration rate than gestodene from
      reference systems. Furthermore, the prodrug was hydrolyzed to the parent drug to
      a high extent during the passage of the skin. CONCLUSIONS: Designing prodrugs to
      the requirements of matrix TDDS is an efficient way of enhancing the transdermal
      drug flux rate.

PMID- 9755896
TI  - Characterization of three crystalline forms (VIII, XI, and XII) and the amorphous
      form (V) of delavirdine mesylate using 13C CP/MAS NMR.
AB  - PURPOSE: The application of solid-state nuclear magnetic resonance (NMR)
      characterization of three crystalline forms (VIII, XI, XII) and the amorphous
      form V of delavirdine mesylate (DLV-M) is presented. METHODS: Conventional 13CCP
      (cross-polarization)/MAS (magic angle spinning) NMR and related spectral editing
      methods were employed. NMR relaxation times (T1pH, T1H, and T1C) were also
      measured. RESULTS: Distinctly different spectral features among the four solid
      forms were observed, indicating high sensitivity of 13C NMR to the variations in
      solid structure. Assessment based on NMR data suggests that both anhydrous forms
      VIII and XI may contain one molecule per asymmetric unit. DLV may adopt a similar
      molecular conformation in the two forms. In contrast, form XII is found to
      consist of two molecules per asymmetric unit. Molecule conformation of DLV in
      forms VIII, XI, and XII is altered from the dominant conformer in solution. The
      amorphous form V may contain DLV molecules of a variety of conformations. NMR
      relaxation times (T1PH, T1H, and T1C) provide valuable information about the
      motional characteristics in these solids. Values and the rank order of T1pH, T1H,
      and T1C also reveal significant differences in local environments and the short
      range order among the four forms. CONCLUSIONS: Four solid forms of DLV-M (V,
      VIII, XI, and XII) can be distinctly differentiated by 13C CP/MAS NMR
      spectroscopy and their structural difference can be partially revealed without
      obtaining single crystal data. NMR relaxation times reveal motion dynamics and
      aid structural elucidation for these forms.

PMID- 9755897
TI  - Self-association properties of monomeric insulin analogs under formulation
      conditions.
AB  - PURPOSE: The purpose of the current study was to investigate the effects of two
      important excipients, zinc and m-cresol, on the self-association properties of a
      series of monomeric insulin analogs. In this way, the effects on formulation
      behavior of individual amino acid substitutions in the C-terminal region of the
      insulin B-chain could be compared. METHODS: The self-association of ten insulin
      analogs was monitored by equilibrium and velocity analytical ultracentrifugation
      under three different conditions: (i) in neutral buffer alone; (ii) in neutral
      buffer containing zinc ion; and (iii) in neutral buffer containing both zinc ion
      and phenolic preservative (a typical condition for insulin formulations). The
      self-association properties of these analogs were compared to those of human
      insulin and the rapid-acting insulin analog Lys(B28)Pro(B29)-human insulin.
      RESULTS: The analogs in the current study exhibited a wide range of association
      properties when examined in neutral buffer alone or in neutral buffer containing
      zinc ion. However, all of these analogs had association properties similar to
      human insulin in the presence of both zinc and m-cresol. Under these formulation
      conditions each analog had an apparent sedimentation coefficient of s* = 2.9-3.1
      S, which corresponds to the insulin hexamer. CONCLUSIONS: Analogs with changes in
      the B27-B29 region of human insulin form soluble hexamers in the presence of both
      zinc and m-cresol, and m-cresol binding overrides the otherwise destabilizing
      effects of these mutations on self assembly.

PMID- 9755898
TI  - Effect of gelation on the chemical stability and conformation of leuprolide.
AB  - PURPOSE: The purpose of this study was to characterize the conformation,
      aggregation, and stability of leuprolide on gelation. METHODS: Infrared spectra
      (FTIR) of leuprolide solutions and gels were collected in water, propylene glycol
      (PG), dimethyl sulfoxide (DMSO), and trifluoroethanol (TFE). Leuprolide solution
      and gel stability data were obtained by SEC and RP-HPLC. RESULTS: Leuprolide was
      induced to gel with increasing peptide concentration, introduction of salts, and
      gentle agitation. Leuprolide dissolved in water (400 mg/ml) demonstrated FTIR
      spectra consisting of two major bands of equal intensity at 1615 cm(-1) and 1630
      cm(-1), similar to inter- and intra-molecular beta-sheet structure in proteins.
      When samples were gently agitated for 24 hours at 25 degrees C, the formulation
      was observed to change from a viscous liquid to an opaque gel with a concomitant
      shift in infrared spectra from the equal intensity bands to mostly 1630 cm(-1),
      indicating a shift to a preferred beta-sheet structure. Incubation of leuprolide
      with 20-200 mM salts at 25 degrees C and 37 degrees C also produced gels ranging
      from clear to cloudy and stringy white precipitates. The gel and precipitate were
      marked by a shift of the predominant beta-sheet band to 1630 cm(-1) and 1615 cm(
      1), respectively. Leuprolide was also observed to gel and/or precipitate in
      mixtures of water, PG or TFE, but not in DMSO. CONCLUSIONS: Birefringence was
      noted in many of the firmer gels. Both solutions and gels demonstrated minimal
      dimer or trimer formation, with no larger order aggregates detected. The chemical
      stability profile of gelled leuprolide was similar to that of the non-gelled
      water formulation by RP-HPLC.

PMID- 9755899
TI  - Degradation kinetics of three gonadorelin analogues: developing a method for
      calculating epimerization parameters.
AB  - PURPOSE: To develop a method for calculating epimerisation parameters, find out
      if the kinetics of the independent reactions can be established, and elucidate
      primary structure-chemical degradation relationships in the degradation kinetics
      of three gonadorelin analogues. METHODS: The influences of pH, temperature, and
      buffer concentration on the degradation of the three gonadorelin analogues
      buserelin, goserelin, and triptorelin were investigated using RP-HPLC. A method
      was developed to calculate epimerisation and hydrolysis rate constants
      independently. RESULTS: Explicit structure-degradation mechanism relations were
      found in the degradation of all three compounds. The L-serine residue was found
      to be involved in both a solvent-catalysed backbone hydrolysis and a hydroxyl
      catalysed epimerisation whereas, the O-tertiary butyl D-serine residue was only
      involved in proton-catalysed ether hydrolysis. The kinetics of identical
      reactions in different analogues were generally comparable. CONCLUSIONS: The
      degradation of the gonadorelin analogues is located at a relatively small number
      of chemical residues and prediction of the degradation mechanisms and kinetics of
      other peptides with similar structural elements appears to be possible.

PMID- 9755900
TI  - Chemical degradation kinetics of recombinant hirudin (HV1) in aqueous solution:
      effect of pH.
AB  - PURPOSE: To gain information on the chemical stability pattern and the kinetics
      of the degradation of recombinant hirudin variant HV1 (rHir), a thrombin-specific
      inhibitor protein of 65 amino acids, in aqueous solution as a function of pH.
      METHODS: Stability of rHir was monitored at 50 degrees C in the framework of a
      classical pH-stability study in aqueous buffers pH 1-9.5. Two capillary
      electrophoresis (CE) protocols were used: one for the kinetics of succinimide
      formation at Asp53-Gly54 (C-terminal tail) and Asp33-Gly34 (loop section), the
      other for the kinetics of rHir degradation. To check for potential effects of
      conformational changes by thermal denaturation, circular dichroism (CD)
      measurements were performed between 25 and 80 degrees C. RESULTS: Throughout the
      pH range studied no effect of thermal denaturation on rHir confirmation at 50
      degrees C was observed. rHir was most stable at a neutral pH whereas, at slightly
      acidic pH, an intermediate stability plateau was found. Both, strongly acidic and
      alkaline conditions led to fast rHir degradation. Depending on the pH of
      degradation, rHir was found to degrade in various combinations of multiple
      parallel and sequential degradation patterns. Special focus was on succinimide
      formation at Asp53-Gly54 (C-terminal tail) and Asp33-Gly34 (loop) and on the
      potential of isoAsp formation in position 53 and 33. CONCLUSIONS: Chemical rHir
      stability in the intermediate pH range depends strongly on succinimide formation.
      At slightly acidic conditions succinimides represent the major degradation
      product (up to 40%). Around neutral pH succinimides react further, presumably by
      isoAsp formation, and concentrations remain low. Relative preference of
      succinimide formation in the C-terminal tail domain versus the loop domain is
      explained by higher backbone flexibility in the tail.

PMID- 9755901
TI  - Automated covariate model building within NONMEM.
AB  - PURPOSE: One important task in population pharmacokinetic/pharmacodynamic model
      building is to identify the relationships between the parameters and demographic
      factors (covariates). The purpose of this study is to present an automated
      procedure that accomplishes this. The benefits of the proposed procedure over
      other commonly used methods are (i) the covariate model is built for all
      parameters simultaneously, (ii) the covariate model is built within the
      population modeling program (NONMEM) giving familiar meaning to the significance
      levels used, (iii) it can appropriately handle covariates that varies over time
      and (iv) it is not dependent on the quality of the posterior Bayes estimates of
      the individual parameter values. For situations in which the computer run-times
      are a limiting factor, a linearization of the non-linear mixed effects model is
      proposed and evaluated. METHODS: The covariate model is built in a stepwise
      fashion in which both linear and non-linear relationships between the parameters
      and covariates are considered. The linearization is basically a linear mixed
      effects model in which the population predictions and their derivatives with
      respect to the parameters are fixed from a model without covariates. The stepwise
      procedure as well as the linearization was evaluated using simulations in which
      the covariates were taken from a real data set. RESULTS: The covariate models
      identified agreed well with what could be expected based on the covariates that
      were actually supported in each of the simulated data sets. The predictive
      performance of the linearized model was close to that of the non-linearized
      model. CONCLUSIONS: The proposed procedure identifies covariate models that are
      close to the model supported by the data set as well as being useful in the
      prediction of new data. The linearized model performs nearly as well as the non
      linearized model.

PMID- 9755902
TI  - Correction for non-ideal tracer pharmacokinetic disposition by disposition
      decomposition analysis (DDA).
AB  - PURPOSE: Pharmacokinetic (PK) studies assume that the tracer's PK is equivalent
      to the parent compound. This assumption is often violated. The aim of this work
      is to present a method enabling the ideal tracer PK, i.e. the PK of the parent
      compound, to be predicted from the non-ideal tracer. METHODS: The procedure uses
      a disposition decomposition-recomposition (DDR) that assumes that the labeling
      mainly changes the elimination kinetics while the distribution kinetics is not
      significantly affected. In the DDR procedure an elimination rate constant
      correction factor (kCOR) is determined from a simultaneously fitting to plasma
      concentration data resulting from an i.v. injection of both the tracer and the
      parent compound. The correction factor is subsequently used to predict the ideal
      tracer PK behavior from the disposition function (i.v. bolus response) of the non
      ideal tracer. RESULTS: The DDR method when applied to plasma level data of
      erythropoietin (r-HuEPO) and its iodinated tracer (125I-r-HuEPO) from a high
      (4000U/kg) and a low (400U/kg) dosing of r-HuEPO in newborn lambs (n=13) resulted
      in excellent agreements in the elimination rate corrected dispositions in all
      cases (r=0.995, SD=0.0095). The correction factor did not show a dose dependence
      (p > 0.05). The correction factors were all larger than 1 (kCOR=1.94, SD=0.519)
      consistent with a reduction in the EPO elimination by the iodination labeling.
      CONCLUSIONS: The DDR tracer correction methodology produces a better
      differentiation of the PK of endogenously produced compounds by correcting for
      the non-ideal PK behavior of chemically produced tracers.

PMID- 9755903
TI  - Correlation of plasma clearance of 54 extensively metabolized drugs between
      humans and rats: mean allometric coefficient of 0.66.
AB  - PURPOSE: To evaluate the distribution of allometric exponents for relationship of
      total plasma clearance of 54 extensively metabolized drugs, with wide-ranging
      linear clearance values, between humans and rats, to provide a rationale for the
      observed data, and to discuss potential significance of the findings. METHODS:
      Human and rat plasma clearance values of 54 drugs with markedly different
      physicochemical properties were obtained from the literature. Standard allometric
      analysis was performed for each drug using both rat and human data. Unbound vs.
      total plasma clearances were obtained for 15 out of 54 drugs and their
      correlations between humans and rats were compared. RESULTS: The mean+/-SD of the
      allometric exponent for the 54 drugs studied is 0.660+/-0.190. The median
      clearance ratio based on unit body weight is 7.41 and the median exponent is
      0.645. Excluding two outliers the correlation coefficient of plasma clearance
      between humans and rats was 0.745 (p < 0.0001). For the 15 drugs, use of unbound
      plasma clearance approach seems to significantly improve the correlation
      coefficient compared to total plasma clearance (0.940 vs. 0.841). CONCLUSIONS:
      The present study indicates that on average, humans and rats may eliminate
      extensively metabolized drugs at a rate similar to that expected from the
      allometric or body surface area relationship of basal metabolic rate between the
      two species. A simple statistical distribution hypothesis is used to rationalize
      the species difference in plasma drug clearance. Rat may serve as an useful
      animal model to predict (unbound) plasma clearance of drugs in humans.

PMID- 9755904
TI  - Enzymatic degradation of luteinizing hormone releasing hormone (LHRH)/[D-Ala6]
      LHRH in lung pneumocytes.
AB  - PURPOSE: To investigate the cellular proteolytic activities of various lung
      pneumocytes using luteinizing hormone releasing hormone (LHRH) and [D-Ala6]-LHRH
      as model peptide substrates. METHODS: HPLC analysis was used to investigate the
      degradation kinetics of LHRH/[D-Ala6]-LHRH and to identify their degradation
      products in isolated lung pneumocytes. RESULTS: Pulmonary macrophages exhibited
      the strongest proteolytic activity against LHRH)/[D-Ala6]-LHRH, followed by type
      II and type I-like pneumocytes. Three major degradation products of LHRH, namely
      LHRH 4-10, LHRH 6-10, and LHRH 7-10, were identified in macrophages and type II
      pneumocytes, whereas in type I-like pneumocytes only the LHRH 7-10 was found. Co
      incubation of the cells with known enzyme inhibitors including captopril (an ACE
      inhibitor), thiorphan (an EP24.11 inhibitor), and EDTA (an EP24.15 inhibitor)
      inhibited the formation of LHRH 4-10, LHRH 7-10, and LHRH 6-10 respectively. In
      all cell types, the degradation rate of [D-Ala6]-LHRH was about 3-8 times lower
      than that of LHRH. This peptide analog was resistant to degradation by EP24.15
      and EP24.11, but was susceptible to ACE. CONCLUSIONS: ACE, EP24.11, and EP24.15
      are the major enzymes responsible for the degradation of LHRH in macrophages and
      type II pneumocytes. The magnitude of peptidase activities in these cell types
      are: EP24.15 > EP24.11 approximately ACE. No EP24.15 or ACE activity was observed
      in type I-like pneumocytes and only a weak EP24.11 activity was detected.

PMID- 9755905
TI  - The roles of depot injection sites and proximal lymph nodes in the presystemic
      absorption of fluphenazine decanoate and fluphenazine: ex vivo experiments in
      rats.
AB  - PURPOSE: The release and presystemic absorption of fluphenazine and its decanoate
      ester from intramuscular depots were investigated. METHODS: Rats were sacrificed
      in groups of three at various times after injection of drug or prodrug in sesame
      oil. Muscle tissues at the injection sites and various lymph nodes were excised.
      Blood (plasma) was harvested by cardiac puncture. RESULTS: Following
      administration of fluphenazine decanoate, the amount of prodrug at the sites of
      injection declined exponentially (half-life 3.4 days). Highest concentrations of
      drug and prodrug were found in iliac and hypogastric lymph nodes nearest to
      injection sites in which both analytes were detectable 28 days post dose. The
      half-life for the decline of fluphenazine from lymph nodes (4.6 days) was similar
      to that from plasma (4.3 days). Following administration of fluphenazine base,
      only 2.8% of the dose remained at the sites of injection after 2 days.
      Concentrations of drug in iliac and hypogastric lymph nodes were comparable to
      those in distal lymph nodes. Fluphenazine concentrations in the lymphatic tissues
      decreased at about the same rate as plasma concentrations. CONCLUSIONS: The rate
      limiting step appeared to be slow partitioning of the decanoate from oily
      deposits at the injection site and proximal lymph nodes with subsequent
      hydrolysis of the ester group.

PMID- 9755906
TI  - Correlating partitioning and caco-2 cell permeability of structurally diverse
      small molecular weight compounds.

PMID- 9755907
TI  - Cellular uptake study of biodegradable nanoparticles in vascular smooth muscle
      cells.

PMID- 9755909
TI  - Endoscopic parathyroidectomy by a gasless approach.
AB  - Endoscopic approach for the treatment of primary hyperparathyroidism is one of
      the new fields of interest for minimally invasive surgery. The removal of the
      parathyroid gland can be achieved either by a gas or gasless technique. Massive
      carbon dioxide (CO2) diffusion and absorption has been reported to occur during
      the gas procedure. Endoscopic techniques that do not rely on CO2 insufflation
      have still to be set. We have developed a new procedure that was offered to 20
      selected patients with a localized parathyroid adenoma. A 3-minute CO2
      insufflation (12 mm Hg) through a conventional trocar inserted under the strap
      muscles is used just to anatomically dissect the virtual thyrotracheal groove.
      Actually, the working space is maintained by means of skin retractors so as to
      allow needlescopic instruments to perform a parathyroid adenomectomy with the
      gasless procedure. In all cases the parathyroid adenoma was removed through a 1.5
      cm skin incision. Quick parathyroid hormone assays always confirmed the removal
      of all pathologic glands and permitted unilateral cervical exploration. Mean
      operative time was 71.7 +/- 35.5 minutes. No complication was registered. At
      follow-up, all patients were normocalcemic. This new endoscopic approach to the
      neck seems to be safe, effective, and cosmetically satisfactory.

PMID- 9755908
TI  - Effect of neutral endopeptidase inhibition on the natriuresis and renal clearance
      of atrial natriuretic peptide in perfused rat kidney.

PMID- 9755910
TI  - Midterm results of thoracoscopic surgery for pulmonary metastases especially from
      colorectal cancers.
AB  - Indications for thoracoscopic metastatectomy remain controversial because not all
      metastatic tumors may be detected without the manual palpation that is possible
      with thoracotomy. However, the accuracy (92%) of preoperative lung imaging in
      patients with one or two lesions led us to re-evaluate thoracoscopic
      metastatectomy with patient survival as the primary end point. Thoracoscopic
      wedge resection using an endoscopic stapling device or video-assisted thoracic
      surgery (VATS) lobectomy was performed in patients with one or two pulmonary
      metastases. Thoracoscopic resection was performed in 27 patients with 22 solitary
      lesions and 5 patients with two lesions. The primary tumors were colorectal
      cancer (15), testicular cancer (3), osteosarcoma (2), and seven other
      histologies. In 5 of 27 patients (18.5%) a thoracoscopic operation was converted
      to a VATS procedure, which requires minithoracotomy to identify metastasis
      primary by digital palpation. The 3-year survival rate for colorectal cancer
      patients who underwent thoracoscopic resection was 56.4%, in comparison to 48.6%
      in historical control thoracotomy patients (n = 16). There was no statistically
      significant difference between the two groups. Thoracoscopic resection of one or
      two colorectal cancer lung metastases results in a survival rate similar to
      standard thoracotomy, and thereby provides an acceptable alternative to this more
      invasive approach.

PMID- 9755911
TI  - Laparoscopic resection of esophageal epiphrenic diverticulum.
AB  - Symptomatic esophageal epiphrenic diverticula are usually repaired with a
      diverticulectomy and esophagomyotomy via a left thoracotomy with substantial
      postoperative pain and morbidity. If a laparoscopic approach could be shown to be
      safe and effective, the decrease in postoperative pain and potentially shorter
      hospital stay would make this technique beneficial. We report three cases
      repaired via a transabdominal approach. The first two cases were done
      laparoscopically. The third case was attempted laparoscopically and completed via
      a midline laparotomy, demonstrating that thoracotomy is not necessary even if
      laparoscopy is not possible. All three patients had long-standing debilitating
      symptoms refractory to standard nonsurgical therapies (botulinum toxin injection,
      pneumatic dilation, antispasmodic medication) with abnormal esophageal motility.
      There was one intraoperative complication of a left pneumothorax that required
      neither laparotomy nor thoracostomy. An esophagram on the first postoperative day
      demonstrated no extravasation and good flow into the stomach. The postoperative
      course was uneventful for all three patients, with the laparoscopic patients
      discharged on the second postoperative day and the laparotomy patient discharged
      on the seventh postoperative day. In conclusion, laparoscopic repair of
      symptomatic esophageal epiphrenic diverticula is a safe and effective technique
      with minimal postoperative pain and morbidity. It should be considered as an
      alternative to the traditional transthoracic approach, and may become the
      standard technique.

PMID- 9755913
TI  - Laparoscopic cholecystectomy facilitated by hydrodissection.
AB  - Hydrodissection has been used in the past in open cholecystectomy to facilitate
      dissection in difficult cases. Injection of 50 mL of saline, with a laparoscopic
      cyst aspiration needle during laparoscopic cholecystectomy between the
      gallbladder and the liver, causes an edematous area 1-1.5 cm thick between the
      gallbladder and the liver. This allows dissection to be carried out prograde and
      retrograde with less bleeding and a much smaller chance of gallbladder
      perforation and the escape of stones. One hundred and thirty-three laparoscopic
      cholecystectomies (LC) utilizing hydrodissection were compared to 48 historical
      controls (HC), comparing blood loss, stone spillage, and dissection time. Blood
      loss was on average less than 5 mL in the LC group and 56 mL in the HC. One case
      of minor biliary spillage occurred in the LC group and 11 gallbladder
      perforations in the HC group. Time taken for the dissection was 6.4 minutes for
      LC and 16 minutes for HC. Laparoscopic hydrodissection was accompanied by less
      bleeding, fewer incidents of gallbladder damage and stone spilling, and a much
      faster dissection time. It can also be performed prograde, which is helpful in
      liver cirrhosis.

PMID- 9755914
TI  - The multimedia CD ROM: an innovative teaching tool for endoscopic sinus surgery.
AB  - The recent explosive growth in the use of endoscopic techniques in the
      performance of surgical procedures has created an important need for educational
      materials on this subject. However, limitations of currently available teaching
      tools frustrate the user and hamper the teaching and spread of these procedures.
      To improve on currently available methods, we developed a CD ROM video atlas of
      techniques in endoscopic sinus surgery (ESS). The multimedia CD ROM video atlas
      combines the best features of the surgical atlas with conventional videotapes.
      The component steps of procedures in ESS are presented to the viewer as brief,
      individual video sequences, accompanied by narration and a text of the highlights
      of each procedure. The use of digital video allows the user to access the segment
      of interest directly, in the order of preference, without having to sift through
      the other segments, as with conventional videocassettes. An interface allows
      control over playback of the video, and sequences can be reviewed instantly.
      Storage capacity of the CD ROM allows up to 60 minutes of video to be stored on
      each disk. The CD ROM combines the best elements of currently available
      educational tools and may represent a new approach for medical education.

PMID- 9755912
TI  - Interval appendectomy for perforated appendicitis in children.
AB  - To determine the efficacy, safety, and cost of managing perforated appendicitis
      with intravenous antibiotics followed by an interval appendectomy, the charts of
      87 children with ruptured appendicitis were retrospectively reviewed. These
      patients were treated with intravenous fluid resuscitation and antibiotics
      (consisting of clindamycin and ceftazidime) and underwent appendectomy, either on
      that admission (n = 46) or as a delayed interval procedure (n = 41). Antibiotics
      in all cases were discontinued either at home or in the hospital after the child
      was a febrile for 48 hours with normal white and differential blood cell counts,
      and the two groups were compared. Seven patients (17%) "failed" the interval
      appendectomy protocol. All but one "failure" was due to the development or
      persistence for >72 hours of a bowel obstruction. The data are described below as
      percent or mean +/- 1 standard deviation. [table: see text] We conclude that
      antibiotics and interval appendectomy is a safe effective alternative for the
      management of perforated appendicitis. When successful, hospitalization, charges,
      and morbidity are less with this approach. A persistent bowel obstruction for 72
      hours is an indication to proceed with appendectomy on admission.

PMID- 9755915
TI  - Laparoscopic treatment of traumatic diaphragmatic hernia.
AB  - Traumatic diaphragmatic hernia is rare, but is of utmost importance due to its
      high morbidity and mortality. It is markedly important in patients with blunt
      abdominal trauma, and diagnosis is difficult because of the numerous associated
      injuries. A patient with few symptoms of chronic traumatic diaphragmatic hernia
      is described, who underwent surgery due to a gastric volvulus. Laparoscopic
      surgery permits repair of these injuries through an abdominal approach, avoiding
      a thoracic incision or selective intubation.

PMID- 9755916
TI  - Gallbladder duplication and laparoscopic management.
AB  - Gallbladder duplication can present a significant challenge to the laparoscopic
      surgeon, primarily due to difficulties with diagnosis and recognition. Previous
      reports of attempted laparoscopic cholecystectomy in patients with gallbladder
      duplication resulted in incomplete or staged multiple procedures. The case report
      of a 35-year-old woman with successful laparoscopic management of symptomatic
      gallbladder duplication is described, emphasizing several important
      considerations. Preoperatively when evaluating radiologic studies a high index of
      suspicion is necessary in interpreting atypical findings. To further evaluate
      these abnormalities, liberal use of preoperative ERCP is helpful, and specific
      endoscopic techniques may be necessary as well. Intraoperatively, the findings
      may be confusing, and cholangiography can help clarify ductular anomalies,
      especially if the gallbladder duplication is contained within a common serosal
      coat. Missing a second gallbladder can result in persistent symptoms
      postoperatively necessitating further surgery. Laparoscopic cholecystectomy in
      the management of gallbladder duplication can be safely done and an awareness is
      necessary to avoid complications or multiple procedures.

PMID- 9755917
TI  - Laparoscopic complete excision of a splenic epidermoid cyst.
AB  - Splenic epidermoid cysts are rare lesions traditionally treated by splenectomy.
      Concerns about overwhelming postsplenectomy sepsis have led to the development of
      splenic preservation procedures in the treatment of cystic diseases of the
      spleen. We present the first case report of successful laparoscopic complete
      excision of a splenic epidermoid cyst.

PMID- 9755918
TI  - Intragastric migration of laparoscopic adjustable gastric band (Lap-Band) for
      morbid obesity.
AB  - The appearance of fistulas and the posterior intragastric inclusion of the
      adjustable silicone Lap-Band prothesis have been described, representing a severe
      complication of the Lap-Band procedure. A 45-year-old patient with severe
      obesity, weighing 115 kg, and having BMI (body max index) of 45 kg/m2 was
      assigned to a protocol to place a Lab-Band in her. An infection in the reservoir
      after 9 months indicated the beginning of the appearance of fistulas. The entire
      adjustable silicone gastric band device eroded inside the stomach between months
      9 and 14 after its placement, resulting in reoperation. The gastric inclusion of
      the Lap-Band device represents a severe complication that requires reoperation,
      and raises concerns about the safety of this new alternative weight reduction
      operation.

PMID- 9755919
TI  - Regarding laparoscopic staging for Hodgkin's disease.

PMID- 9755921
TI  - Bibliography.

PMID- 9755920
TI  - Regarding laparoscopy-associated mesenteric vascular events: descript of an
      evolving clinical syndrome.

PMID- 9755922
TI  - Tuberculosis 2000: problems and solutions.
AB  - The incidence of tuberculosis is expected to increase, from 8.8 million cases in
      1995, to 10.2 million cases by the year 2000 and 11.9 million by 2005. Three
      million deaths due to tuberculosis occurred in 1995, and 3.5 million can be
      expected in the year 2000. The most important causes of the world-wide increase
      in tuberculosis are: 1) non-compliance with control programmes; 2) inadequate
      diagnosis and treatment; 3) migration; 4) endemic human immunodeficiency virus
      (HIV); 5) ambulatory and self-administered treatment. In the 1970s it was stated
      that treatment needed to be supervised-a recommendation that went unheeded. A
      number of fundamental changes should be introduced in order to make treatment
      effective, to cure patients and thus to arrest the transmission of the disease:
      1) supervision during the whole period antituberculosis drugs are taken, and 2)
      hospitalization during the initial treatment stage for all groups at risk. It is
      already 50 years since the first antituberculosis drugs were discovered;
      effective treatments capable of curing all patients in 6 months have been
      available for the last 25 years, and the result is failure plus a growing
      mortality curve at the beginning of the twenty-first century. If we wish to alter
      this trend, we need trained doctors all over the world who possess enough
      clinical knowledge of tuberculosis; hospitalization for specific groups of
      tuberculosis patients; true supervision during the whole treatment period; fixed
      dose combinations of drugs; and prophylaxis or preventive treatment whenever
      possible. We also need to take into account other factors such as drug
      resistance, endemic HIV, and migration.

PMID- 9755923
TI  - Intensive short course chemotherapy in the management of tuberculous meningitis.
AB  - SETTING: Short course chemotherapy for tuberculous meningitis (TBM) is advocated
      by several groups, but relatively few children have been so treated and followed
      up. METHODS: A prospective, observational study of isoniazid (INH), rifampicin
      (RMP) and ethionamide (ETH) in a dosage of 20 mg/kg, and pyrazinamide (PZA) 40
      mg/kg, all given once daily in hospital for 6 months. Surviving children were
      followed up for a year after discharge. RESULTS: Ninety five children, 39 (41%)
      at stage III, 52 (55%) at stage II and 4 (4%) at stage I TBM were studied. Ten
      (26%) at stage III and 3 (6%) at stage II died before completion of therapy. Five
      surviving children (6%) moved on discharge and were untraceable; seven children
      (9%) were lost during follow up and three were inadvertently restarted on
      antituberculosis therapy. Two children with severe stage III disease died after
      discharge. One child experienced a probable disease recrudescence 1 month after
      discharge. Eighteen children (20%) developed a mildly elevated serum bilirubin
      concentration during the first month of treatment. In five of these children INH,
      RMP, ETH and PZA were stopped and streptomycin (SM) and ethambutol substituted.
      In all cases the original treatment was restarted without incident. One child
      developed overt jaundice after 5 months of treatment due to hepatitis A
      infection. CONCLUSIONS: Our experience suggests that young children with TBM can
      be safely treated for 6 months with high doses of antituberculosis agents without
      overt hepatotoxicity and with a low risk of relapse.

PMID- 9755924
TI  - Factors determining the outcome of treatment of adult smear-positive tuberculosis
      cases in The Gambia.
AB  - SETTING: Health centres in The Gambia, West Africa. OBJECTIVES: To identify
      factors determining the outcome of treatment of adult tuberculosis cases in a
      Tuberculosis Control Programme using directly observed treatment. DESIGN:
      Information on the outcome of treatment was collected on all tuberculosis cases
      registered with the Tuberculosis Control Programme in 1994 and 1995 and treated
      under supervision by tuberculosis control staff, nurses or village health
      workers. Treatment outcome was recorded as cured, completed treatment, failed,
      defaulted or died. Transferred-out patients were traced and their treatment
      outcome recorded at the health centre where they had last been seen. RESULTS:
      Data were analysed for 1357 adult smear-positive tuberculosis cases. Sputum smear
      conversion 2 months after the start of treatment was observed in 90% of smear
      positive cases and was more likely to occur if the initial bacterial load in the
      sputum was low. The total cure rate was 74.6%. Female tuberculosis patients were
      more likely to achieve cure than males. Adjusting for sex, the cure rate was
      higher when treatment was provided by tuberculosis control staff in the main
      health centres rather than by nurses or village health workers at the peripheral
      level (odds ratio [OR] = 1.60, 95% confidence interval [CI] 1.23-2.09). The
      absence of sputum smear conversion after 2 months of chemotherapy was associated
      with defaulting later during treatment (OR = 2.0, 95% CI 1.15-3.57). Adjusting
      for age and sex, the death rate during treatment was higher in human
      immunodeficiency virus (HIV) positive than in HIV-negative tuberculosis patients.
      CONCLUSION: Directly observed treatment is an effective intervention for
      improving adherence of tuberculosis patients to treatment in a resource-poor
      country, provided that drugs are effectively delivered to the most peripheral
      level, and that health staff are adequately trained and regularly supervised.
      Patients with high bacterial load in initial sputum smears need to be closely
      supervised, as they are more likely to default from treatment.

PMID- 9755925
TI  - Plasma zinc status in Indian childhood tuberculosis: impact of antituberculosis
      therapy.
AB  - SETTING: Department of Paediatrics and Biochemistry, Postgraduate Institute of
      Medical Education and Research, Chandigarh, India. OBJECTIVE: To assess the
      plasma zinc status in children with tuberculosis and to correlate it with
      nutritional status, activity and severity of disease in relation to
      antituberculosis therapy. DESIGN: The plasma zinc status of 50 children with
      different forms of tuberculosis was compared with 10 healthy and 10 malnourished
      children without tuberculosis at 0, 1, 2, 3 and 6 months of antituberculosis
      therapy. RESULT: The mean plasma zinc concentration in children with pulmonary
      tuberculosis (n = 20) was 68.65+/-2.50 microg/dl, central nervous system (CNS)
      tuberculosis (n = 10) was 64.20+/-3.82 microg/dl, tuberculous lymphadenitis (n =
      10) was 63.2+/-3.77 microg/dl and disseminated tuberculosis (n = 10) was 59.0+/
      2.75 microg/dl at 0 months. The mean plasma zinc level of healthy children was
      129.10+/-3.01 microg/dl and in malnourished non-tuberculous children it was
      108.40+/-3.16 microg/dl. Thus children with tuberculosis had significantly lower
      plasma zinc level than those without tuberculosis, irrespective of their
      nutritional status (P < 0.001). There was a significant rise in zinc level at the
      end of 6 months of antituberculosis therapy (P < 0.001). CONCLUSION: Plasma zinc
      status may prove to be a good objective marker for monitoring the severity of the
      disease and the response to therapy.

PMID- 9755926
TI  - The cost of tuberculosis to patients in Sierra Leone's war zone.
AB  - OBJECTIVE: To evaluate how the extreme poverty of the patients and the poor
      salaries of the staff combined to increase the cost of treatment to patients
      within the subsidised national tuberculosis programme in Sierra Leone.
      DESIGN/SETTING: From September to December of 1994, semi-structured interviews
      were conducted with 72 patients and 17 staff of the National Leprosy and
      Tuberculosis Control Programme of Sierra Leone, a screening and treatment
      programme funded by international donors. RESULTS: Although some extra costs were
      indeed incurred within the subsidized national tuberculosis treatment programme,
      they were much lower than those incurred during the pre-programme period when the
      patients sought intermittent help from a wide range of traditional and biomedical
      sources within the plural healing continuum. The national politico-economic
      crisis, and the consequent poverty of most patients, impeded compliance with and
      sustainability of treatment, even within the formal subsidised treatment
      programme. CONCLUSIONS: More money was spent by patients on treatment in the
      months/years preceding entry into the national tuberculosis programme. Many
      factors retarded entry, including poor communications, misinformation,
      malpractice by health professionals, and displacement resulting from chronic
      internal warfare. The war intensified all factors that predispose to tuberculosis
      and retarded access to treatment. Supra-programme cost, or 'corruption,' was
      minimal due to the poverty of health professionals, with a few salient
      exceptions.

PMID- 9755927
TI  - Drug-resistant tuberculosis in Budapest.
AB  - SETTING: Sixteen districts of Budapest, Hungary. OBJECTIVE: To determine the
      frequency of primary and secondary drug resistance, and to recommend treatment
      regimens. DESIGN: A retrospective survey. METHODS: Mycobacterium tuberculosis
      isolates were collected from 264 newly diagnosed and 147 previously treated
      patients. All strains were tested against isoniazid (INH), rifampicin (RIF),
      streptomycin (SM) and ethambutol (EMB) using the proportion method. Bacteriologic
      examinations were performed in the Diagnostic Laboratory of the Koranyi National
      Institute for Tuberculosis and Pulmonology in Budapest. RESULTS: Primary
      resistance to INH alone was 4%, to SM alone 2%, to RIF alone 0.4%, to INH and SM
      1%, and to INH, RIF, SM and EMB 0.4%. Of the isolates of 78 relapse cases, six
      (8%) were resistant to INH alone, one (1%) to INH and RIF, two (3%) to INH, RIF,
      SM and EMB. Of the isolates of 69 patients notified with active tuberculosis for
      over a year, 51 (74%) were susceptible to the drugs tested. CONCLUSION: Based on
      the level of primary drug resistance as well as on the resistance pattern of
      relapse cases, it is recommended to start the treatment of newly detected and
      relapse cases with four drugs. The high rate of chronic cases with susceptible
      strains can be explained by poor compliance. To prevent development of resistant
      cases and to achieve good compliance, it is necessary to apply direct observation
      of treatment in all types of patients.

PMID- 9755928
TI  - Metronidazole has no antibacterial effect in Cornell model murine tuberculosis.
AB  - SETTING: Experiments in vitro on the bactericidal activity of metronidazole and
      in the Cornell model of murine tuberculosis. OBJECTIVE: To assess the sterilising
      activity of maximal metronidazole dosage and its activity against bacilli held
      dormant by immunity in the mouse. DESIGN: In vitro experiments showed that
      metronidazole was only bactericidal at attainable concentrations (50-100
      microg/ml) under anaerobic conditions. In the Cornell model, isoniazid 25 mg/kg
      and high dosage pyrazinamide 1000 mg/kg was given in the diet with and without
      1500 mg/kg metronidazole for the initial 14 weeks of sterilising chemotherapy. In
      the subsequent sterile state, metronidazole at 0, 100 and 250 mg/kg was given by
      daily gavage for 6 weeks. Finally, the mice were given 3 weeks of high dosage
      steroids and their organs were cultured in selective liquid medium. RESULTS:
      Metronidazole had no activity either in the initial sterilising phase or in the
      subsequent sterile state. CONCLUSION: The O2 tension in the cellular lesions of
      murine tuberculosis is unlikely to be sufficiently low to allow metronidazole to
      act. Its activity should be assessed in caseous lesions.

PMID- 9755930
TI  - E-test for susceptibility testing of Mycobacterium tuberculosis.
AB  - SETTING: Initial isolates should be tested for drug susceptibility to confirm the
      anticipated effectiveness of chemotherapy. OBJECTIVE: To evaluate E-test strips
      for susceptibility testing of Mycobacterium tuberculosis. DESIGN: A proportion
      method using Lowenstein-Jensen medium and the Bactec radiometric system were
      compared with the E-test (isoniazid [INH], rifampicin [RMP], ethambutol [EMB] and
      streptomycin [SM]). RESULTS: For 73 of the 81 M. tuberculosis isolates (90.1%)
      the proportion and E-test methods yielded concordant susceptibility results
      against all four antimicrobial agents tested. Of these 73 strains, 69 were fully
      susceptible; the four isolates showing resistance to antimicrobial drugs by both
      methods were also resistant when tested by Bactec 460TB. While the proportion
      method indicated susceptibility for the eight remaining strains, E-test results
      showed mono EMB resistance in five strains, INH resistance for two isolates
      (including one isolate resistant to EMB plus INH), and for one strain E-test
      yielded resistance to EMB and SM. Using Bactec as the reference method, the E
      test resulted in false resistance in eight strains and no false susceptibility.
      CONCLUSION: Due to a substantial rate of false resistance, this method cannot be
      recommended at present for practical use in clinical laboratories.

PMID- 9755929
TI  - Molecular epidemiology of tuberculosis in Cuba outside of Havana, July 1994-June
      1995: utility of spoligotyping versus IS6110 restriction fragment length
      polymorphism.
AB  - SETTING: Molecular typing has become an important tool for examining the extent
      of active transmission of tuberculosis. OBJECTIVES: To examine transmission of
      tuberculosis in Cuba using IS6110 restriction fragment length polymorphism (RFLP)
      typing and to evaluate the utility of spoligotyping. DESIGN: One hundred and
      sixty Mycobacterium tuberculosis strains isolated over a one year period in Cuba
      were subjected to RFLP and spoligotyping. RESULTS: Forty-eight percent of the
      isolates were found in 19 clusters of strains with identical RFLP patterns. In
      general, cluster sizes were limited, except for two large institutional
      outbreaks. Age was strongly inversely correlated to clustering. Most streptomycin
      resistant isolates were found in clusters. Fifteen spoligotype clusters comprised
      78% of the isolates. Significantly different IS6110 RFLP types subdivided 11
      spoligotype clusters, whereas none of the IS6110 clusters were subdivided by
      spoligotyping. CONCLUSIONS: Considering the short study period, 48% clustering is
      high, indicating that recent transmission plays an important role in Cuba.
      Although resistance is still a minor problem, transmission of streptomycin
      resistant strains occurs. The high polymorphism observed with IS6110 RFLP
      indicates that this marker is useful for future molecular epidemiological studies
      in Cuba. Spoligotyping appeared less suitable for population-based studies.

PMID- 9755931
TI  - Limitations and requirements for quality control of sputum smear microscopy for
      acid-fast bacilli.
AB  - Sputum microscopy for acid-fast bacilli (AFB) is considered to be the most
      appropriate method for case-finding in a tuberculosis (TB) control programme. It
      is usually carried out by general technicians, often after minimal training.
      Quality control of their results therefore seems indispensable. The methods
      advocated for quality control are reviewed. Controls by culture leave too much
      uncertainty because of big differences in technical characteristics of the
      methods. Sets of smears sent out by a central laboratory can only be used to
      assess capability. Rechecking routine smears allows daily performance to be
      appraised and may be a strong motivation, but feasibility may be a problem. Based
      on our experience, we describe the technical requirements for cross-checking of
      routine smears. Counter-checking slides with discordant results is crucial for
      accurate assessments. A sample size should strike a balance between statistical
      accuracy and the man-power needed. Indicators for evaluation are proposed that
      allow discrimination of error gradings, to be used in a phased manner with
      priority at first being given to false negatives and false positives that pass
      the threshold for clinical decision-making. Estimates of critical values with
      suggestions about their interpretation are placed in the context of supervising
      TB laboratories.

PMID- 9755932
TI  - Pneumonia due to Leptospira spp.: results of an epidemiological and clinical
      study.
AB  - OBJECTIVE: To evaluate the prevalence of Leptospira spp. infections in a
      population of in- and out-patients with community acquired pneumonia (CAP) and
      the incidence of leptospiral pneumonia. DESIGN AND RESULTS: Of 176 patients
      infected with CAP who were evaluated for the presence of Leptospira spp. as
      causative agent, 10 were found positive for leptospiral antibodies (prevalence
      rate: 5.7%), but seroconversion was observed in only one case (incidence rate:
      0.6%). The patient had had recent contact with possibly contaminated water. She
      had pulmonary involvement and signs of mild hepatic damage, but recovered fully.
      CONCLUSION: The authors highlight the importance of testing for leptospirosis in
      case of pneumonia in endemic areas where the more common causative pathogens for
      CAP can not be documented and when initial empiric therapy is ineffective.

PMID- 9755933
TI  - Serum vitamin A levels during tuberculosis and human immunodeficiency virus
      infection.
AB  - Vitamin A deficiency during tuberculosis and human immunodeficiency virus (HIV)
      infection has not been characterized. A cross-sectional study was conducted among
      HIV-infected adults with tuberculosis in Butare, Rwanda, in which 29% of the
      subjects had serum vitamin A levels consistent with deficiency (<1.05
      micromol/L). Women had mean serum vitamin A levels of 1.22+/-0.45, compared with
      1.47+/-0.68 in men (P < 0.07). A total of 37% of subjects with recent weight loss
      had vitamin A levels consistent with deficiency, compared with 14% of subjects
      without weight loss (P < 0.02). This study suggests that vitamin A deficiency is
      common among adults with tuberculosis and HIV infection in Rwanda.

PMID- 9755934
TI  - Multidrug-resistant tuberculous meningitis in a health care worker.

PMID- 9755935
TI  - Implantation of tuberculosis into the chest wall as a complication of fine needle
      aspiration of pulmonary tuberculoma.

PMID- 9755936
TI  - TB and HIV in Bolivia.

PMID- 9755937
TI  - Measured molecular coherent scattering form factors of animal tissues, plastics
      and human breast tissue.
AB  - Photon scattering angular distributions from various animal tissues were measured
      at two energies of a monochromatic synchrotron x-ray beam. Two plastics and human
      breast tissue were also measured. From these two measurements, the molecular
      coherent scattering form factor of each material was extracted. A new data
      analysis technique that uses Monte Carlo based corrections for air scattering,
      incoherent scattering and multiple scattering was used. The form factors of the
      16 materials are presented in tabular form, suitable for use in computer
      calculations.

PMID- 9755938
TI  - Accuracy of subsurface temperature distributions computed from pulsed
      photothermal radiometry.
AB  - Pulsed photothermal radiometry (PPTR) is a non-contact method for determining the
      temperature increase in subsurface chromophore layers immediately following
      pulsed laser irradiation. In this paper the inherent limitations of PPTR are
      identified. A time record of infrared emission from a test material due to laser
      heating of a subsurface chromophore layer is calculated and used as input data
      for a non-negatively constrained conjugate gradient algorithm. Position and
      magnitude of temperature increase in a model chromophore layer immediately
      following pulsed laser irradiation are computed. Differences between simulated
      and computed temperature increase are reported as a function of thickness, depth
      and signal-to-noise ratio (SNR). The average depth of the chromophore layer and
      integral of temperature increase in the test material are accurately predicted by
      the algorithm. When the thickness/depth ratio is less than 25%, the computed peak
      temperature increase is always significantly less than the true value. Moreover,
      the computed thickness of the chromophore layer is much larger than the true
      value. The accuracy of the computed subsurface temperature distribution is
      investigated with the singular value decomposition of the kernel matrix. The
      relatively small number of right singular vectors that may be used (8% of the
      rank of the kernel matrix) to represent the simulated temperature increase in the
      test material limits the accuracy of PPTR. We show that relative error between
      simulated and computed temperature increase is essentially constant for a
      particular thickness/depth ratio.

PMID- 9755939
TI  - Near-infrared optical properties of ex vivo human skin and subcutaneous tissues
      measured using the Monte Carlo inversion technique.
AB  - The absorption and transport scattering coefficients of caucasian and negroid
      dermis, subdermal fat and muscle have been measured for all wavelengths between
      620 and 1000 nm. Samples of tissue 2 mm thick were measured ex vivo to determine
      their reflectance and transmittance. A Monte Carlo model of the measurement
      system and light transport in tissue was then used to recover the optical
      coefficients. The sample reflectance and transmittance were measured using a
      single integrating sphere 'comparison' method. This has the advantage over
      conventional double-sphere techniques in that no corrections are required for
      sphere properties, and so measurements sufficiently accurate to recover the
      absorption coefficient reliably could be made. The optical properties of
      caucasian dermis were found to be approximately twice those of the underlying fat
      layer. At 633 nm, the mean optical properties over 12 samples were 0.033 mm(-1)
      and 0.013 mm(-1) for absorption coefficient and 2.73 mm(-1) and 1.26 mm(-1) for
      transport scattering coefficient for caucasian dermis and the underlying fat
      layer respectively. The transport scattering coefficient for all biological
      samples showed a monotonic decrease with increasing wavelength. The method was
      calibrated using solid tissue phantoms and by comparison with a temporally
      resolved technique.

PMID- 9755940
TI  - Effect of temperature on the optical properties of ex vivo human dermis and
      subdermis.
AB  - The effect of temperature on the optical properties of human dermis and subdermis
      as a function of near-infrared wavelength has been studied between 25 degrees C
      and 40 degrees C. Measurements were performed ex vivo on a total of nine skin
      samples taken from the abdomen of three individuals. The results show a
      reproducible effect of temperature on the transport scattering coefficient of
      dermis and subdermis. The relative change of the transport scattering coefficient
      showed an increase for dermis ((4.7+/-0.5) x 10(-3) degrees C(-1)) and a decrease
      for subdermis ((-1.4+/-0.28) x 10(-3) degrees C(-1)). Note that the magnitude of
      the temperature coefficient of scattering was greater for dermis than subdermis.
      A reproducible effect of temperature on the absorption coefficient could not be
      found within experimental errors. System reproducibility in transport scattering
      coefficient with repeated removal and repositioning of the same tissue sample at
      the same temperature was excellent at +/-0.35% for all measurements. This
      reproducibility enabled such small changes in scattering coefficient to be
      detected.

PMID- 9755941
TI  - Calculation of microplanar beam dose profiles in a tissue/lung/tissue phantom.
AB  - Recent advances in synchrotron generated x-ray beams with a high fluence rate
      permit investigation of the application of an array of closely spaced, parallel
      or converging microplanar beams in radiotherapy. The proposed technique takes
      advantage of the hypothesized repair mechanism of capillary cells between
      alternate microbeam zones, which regenerates the lethally irradiated endothelial
      cells. The lateral and depth doses of 100 keV microplanar beams are investigated
      for different beam dimensions and spacings in a tissue, lung and
      tissue/lung/tissue phantom. The EGS4 Monte Carlo code is used to calculate dose
      profiles at different depths and bundles of beams (up to 20 x 20 cm square cross
      section). The maximum dose on the beam axis (peak) and the minimum interbeam dose
      (valley) are compared at different depths, bundles, heights, widths and beam
      spacings.

PMID- 9755942
TI  - The calibration of therapy level electron beam ionization chambers in terms of
      absorbed dose to water.
AB  - During 1998, NPL plans to introduce the world's first absorbed dose calibration
      service for electron beam radiotherapy. The service will be based on the primary
      standard graphite calorimeter, and will enable the direct calibration of electron
      ionization chambers, without reference to air kerma standards. This calibration
      is a two-step process. Firstly, a set of NACP-designed parallel-plate reference
      chambers have been calibrated against the calorimeter over the last few years.
      These chambers are then used to calibrate user chambers by direct comparison in a
      water phantom under standard conditions. This paper describes the calibration of
      the reference chambers against the calorimeter and the derivation of absorbed
      dose to water calibration factors (with an estimated uncertainty in this
      calibration of +/-1.50% at the 95% confidence level).

PMID- 9755943
TI  - Generation of discrete beam-intensity modulation by dynamic multileaf collimation
      under minimum leaf separation constraints.
AB  - An algorithm to generate discrete beam-intensity modulation by dynamic multileaf
      collimation is presented which incorporates constraints on minimum allowed leaf
      separations. MLC positioning information is derived simultaneously for all leaf
      pairs and back-up diaphragms as they progress across the field. A feedback
      mechanism allows corrections to be applied to eliminate potential violations of
      minimum separation conditions and any underexposure in the interleaf tongue-and
      groove region as they are encountered. The resulting motion correctly delivers
      the intended modulation and is physically realizable. Implementation of the
      algorithm is described. Results of the algorithm can also alternatively be
      interpreted as defining a series of static fields to deliver the same modulation.

PMID- 9755944
TI  - Use of the Cimmino algorithm and continuous approximation for the dose deposition
      kernel in the inverse problem of radiation treatment planning.
AB  - An approximate continuous data fitting model for the dose deposition kernel was
      developed. The model uses a discrete Fourier transform to interpolate dose values
      in patient space and intensity distribution in treatment space. The continuous
      kernel was applied to the inverse problem of radiation treatment planning. In the
      problem a prescribed dose distribution was to be created using intensity
      modulation of several fields. The Cimmino algorithm suitable for solving large
      systems of inequalities was adapted. Upper and lower dose constraints for
      planning target volume (PTV) and organs at risk (OAR) can be implemented into the
      algorithm. Using continuous and discrete kernels an intensity modulation was
      computed in a two-dimensional phantom with a PTV and low-dose region, and in the
      real three-dimensional patient planning. Intensity modulations obtained using
      continuous and discrete kernels were in good agreement.

PMID- 9755945
TI  - Phase mammography--a new technique for breast investigation.
AB  - A new phase radiography technique for investigation and diagnosis of neoplasms in
      breast tissue is proposed. Forty-four mammography samples with adenocarcinoma
      that had been prepared after mastectomy were tested in a new phase radiography
      device. It was shown that the phase images manifest the changes in parenchyma
      structure due to malignancy and microcalcifications up to 50 microm in size.
      Results obtained were verified by histological examination. A contrast of the
      phase images of small microcalcifications and distortions of the stroma
      architecture ranges up to 40-60%; spatial resolution is about 20 microm. The
      proposed technique offers outstanding possibilities for digital mammography. The
      small and large details of structure manifest themselves with practically the
      same contrast. Phase images differ from those obtained in mammography and many
      details still require further decoding.

PMID- 9755946
TI  - Mammography spectrum measurement using an x-ray diffraction device.
AB  - The use of a diffraction spectrometer developed by Deslattes for the
      determination of mammographic kV is extended to the measurement of accurate,
      relative x-ray spectra. Raw x-ray spectra (photon fluence versus energy) are
      determined by passing an x-ray beam through a bent quartz diffraction crystal,
      and the diffracted x-rays are detected by an x-ray intensifying screen coupled to
      a charge coupled device. Two nonlinear correction procedures, one operating on
      the energy axis and the other operating on the fluence axis, are described and
      performed on measured x-ray spectra. The corrected x-ray spectra are compared
      against tabulated x-ray spectra measured under nearly identical conditions.
      Results indicate that the current device is capable of producing accurate
      relative x-ray spectral measurements in the energy region from 12 keV to 40 keV,
      which represents most of the screen-film mammography energy range. Twelve keV is
      the low-energy cut-off, due to the design geometry of the device. The
      spectrometer was also used to determine the energy-dependent x-ray mass
      attenuation coefficients for aluminium, with excellent results in the 12-30 keV
      range. Additional utility of the device for accurately determining the
      attenuation characteristics of various normal and abnormal breast tissues and
      phantom substitutes is anticipated.

PMID- 9755947
TI  - Monte Carlo modelling of an extended DXA technique.
AB  - The precision achieved in measuring bone mineral density (BMD) by commercial dual
      energy x-ray absorptiometry (DXA) machines is typically better than 1%, but
      accuracy is considerably worse. Errors, due to inhomogeneous distributions of
      fat, of up to 10% have been reported. These errors arise because the DXA
      technique assumes a two-component model for the human body, i.e. bone mineral and
      soft tissue. This paper describes an extended DXA technique that uses a three
      component model of human tissue and significantly reduces errors due to
      inhomogeneous fat distribution. In addition to two x-ray transmission
      measurements, a measurement of the path length of the x-ray beam within the
      patient is required. This provides a third equation, i.e. T = ts + tb + tf where
      T, ts, tb and tf are the total, lean soft tissue, bone mineral and fatty tissue
      thicknesses respectively. Monte Carlo modelling was undertaken to make a
      comparison of the standard and extended DXA techniques in the presence of
      inhomogeneous fat distribution. Two geometries of varying complexity were
      simulated. In each case the extended DXA technique produced BMD measurements that
      were independent of soft tissue composition whereas the standard technique
      produced BMD measurements that were strongly dependent on soft tissue
      composition. For example, in one case, the gradients of the plots of BMD versus
      fractional fat content were for standard DXA (-0.183+/-0.037) g cm(-2) and for
      extended DXA (0.027+/-0.044) g cm(-2). In all cases the extended DXA method
      produced more accurate but less precise results than the standard DXA technique.

PMID- 9755948
TI  - MRI thermometry in phantoms by use of the proton resonance frequency shift
      method: application to interstitial laser thermotherapy.
AB  - In this work the temperature dependence of the proton resonance frequency was
      assessed in agarose gel with a high melting temperature (95 degrees C) and in
      porcine liver in vitro at temperatures relevant to thermotherapy (25-80 degrees
      C). Furthermore, an optically tissue-like agarose gel phantom was developed and
      evaluated for use in MRI. The phantom was used to visualize temperature
      distributions from a diffusing laser fibre by means of the proton resonance
      frequency shift method. An approximately linear relationship (0.0085 ppm degrees
      C(-1)) between proton resonance frequency shift and temperature change was found
      for agarose gel, whereas deviations from a linear relationship were observed for
      porcine liver. The optically tissue-like agarose gel allowed reliable MRI
      temperature monitoring, and the MR relaxation times (T1 and T2) and the optical
      properties were found to be independently alterable. Temperature distributions
      around a diffusing laser fibre, during irradiation and subsequent cooling, were
      assessed with high spatial resolution (voxel size = 4.3 mm3) and with random
      uncertainties ranging from 0.3 degrees C to 1.4 degrees C (1 SD) with a 40 s scan
      time.

PMID- 9755949
TI  - A phantom study evaluating the quantitative aspect of 3D PET imaging of the
      brain.
AB  - Phantom studies are used to develop a reliable quantitative data processing
      protocol for 3D PET brain scanning for conditions typically encountered in FDG
      and neuroreceptor brain imaging. These protocols often span several half-lives of
      the injected radiotracer thus resulting in a greatly varying statistical content
      of the acquired data over the study duration. Detector normalization, scatter
      correction and their interplay over a wide range of statistical content of
      acquired data were evaluated. Overall sensitivity calibration factors were
      determined after all other quantification corrections were applied to the data.
      The result is an optimum data processing protocol that includes an iterative
      convolution subtraction scatter correction method, a normalization procedure that
      takes into account the geometric properties of the scanner and a region of
      interest based calibration procedure, applied in this order. This protocol yields
      a 3D PET quantification accuracy within approximately 3% of independently
      measured concentration values for scanning conditions that include variation in
      the number of acquired counts from one million to several hundred millions and
      variation in size and shape from a 20 cm diameter phantom to a tapered phantom
      with minimum cross section of 3.7 x 14.5 cm2. This performance is comparable with
      that of the 2D acquisition mode.

PMID- 9755950
TI  - Mathematical model of the CA1 region of the rat hippocampus.
AB  - A mathematical transcription of the intrinsic circuit of the CA1 region of the
      rat dorsal hippocampus was made and the model parameters adjusted according to
      experimental data from intracellular recordings and single channel kinetics. This
      model was able to simulate well the profile of the field potentials recorded
      extracellularly and the well known phenomenon of the paired-pulse depression. The
      results suggest that the depression of the second pulse, often interpreted in the
      literature as resulting from GABA(A) inhibition, can also be due to 'shunting'
      effects on the CA1 pyramids' membrane. The rhythmic oscillations of the field
      potential (EEG) was obtained as an emergent property of the network dynamics. The
      frequency of the field oscillation followed the main synaptic input in the region
      (Schaffer collaterals).

PMID- 9755951
TI  - Measurement of off-axis and peripheral skin dose using radiochromic film.
AB  - A radiotheraphy skin dose profile can be obtained with radiochromic film. The
      central axis skin dose relative to Dmax for a 10 x 10 cm2 field size was found to
      be 22%, 17% and 15.5% for 6 MV, 10 MV and 18 MV photon beams. Peripheral dose
      increased with increasing field size. At 10 MV the skin dose 2 cm outside the
      geometric field edge was measured as 6%, 10% and 17% for 10 x 10 cm2, 20 x 20 cm2
      and 30 x 30 cm2 field sizes respectively. Off-axis skin dose decreased as
      distance increased from central axis for fields with Perspex block trays. For a
      20 x 20 cm2 field, an approximately 5-8% drop in percentage skin dose was
      observed from central axis to the beam edge.

PMID- 9755952
TI  - Dosimetric evaluation of the Siemens Virtual Wedge.
AB  - Recently, Siemens has introduced its Virtual Wedge (VW). On a Mevatron
      accelerator, this option generates a wedge-like dose profile by moving a
      collimator jaw at constant speed while varying the dose rate. In this paper the
      formalism is given that is used to deliver a wedge profile and from that the
      expressions for possible combinations of wedge angle, field size and delivered
      MUs are derived. Also the time needed to deliver a VW field is calculated. An
      effective attenuation coefficient mu is used in the implementation. For three
      beam energies, values of mu are determined in order to get VW angles that are as
      close as possible to the hard wedge angles, over a wide range of field sizes and
      wedge angles. Linearity with number of MUs and gantry angle dependence of the
      generated dose profiles were checked. These factors did not have a significant
      influence on the VW dose profiles. Wedge factors should be close to unity in the
      VW implementation. We have measured a number of wedge factors and found that they
      start to deviate from 1 with more than 1% for large wedge angles and field sizes,
      up to 3.5% for a 19 x 19 cm2, 60 degrees VW field. The Virtual Wedge turned out
      to be a reliable tool that can be used clinically, provided that it can be
      handled by the treatment planning system. It provides extra flexibility and
      usually results in shorter beam on times.

PMID- 9755953
TI  - Quality assurance of the dose delivered by small radiation segments.
AB  - The use of intensity modulation with multiple static fields has been suggested by
      many authors as a way to achieve highly conformal fields in radiotherapy.
      However, quality assurance of linear accelerators is generally done only for beam
      segments of 100 MU or higher, and by measuring beam profiles once the beam has
      stabilized. We propose a set of measurements to check the stability of dose
      delivery in small segments, and present measured data from three radiotherapy
      centres. The dose delivered per monitor unit, MU, was measured for various
      numbers of MU segments. The field flatness and symmetry were measured using
      either photographic films that are subsequently scanned by a densitometer, or by
      using a diode array. We performed the set of measurements at the three
      radiotherapy centres on a set of five different Philips SL accelerators with
      energies of 6 MV, 8 MV, 10 MV and 18 MV. The dose per monitor unit over the range
      of 1 to 100 MU was found to be accurate to within +/-5% of the nominal dose per
      monitor unit as defined for the delivery of 100 MU for all the energies. For four
      out of the five accelerators the dose per monitor unit over the same range was
      even found to be accurate to within +/-2%. The flatness and symmetry were in some
      cases found to be larger for small segments by a maximum of 9% of the
      flatness/symmetry for large segments. The result of this study provides the
      dosimetric evidence that the delivery of small segment doses as top-up fields for
      beam intensity modulation is feasible. However, it should be stressed that linear
      accelerators have different characteristics for the delivery of small segments,
      hence this type of measurement should be performed for each machine before the
      delivery of small dose segments is approved. In some cases it may be advisable to
      use a low pulse repetition frequency (PRF) to obtain more accurate dose delivery
      of small segments.

PMID- 9755954
TI  - Automated detection of BB pixel clusters in digital fluoroscopic images.
AB  - Small ball bearings (BBs) are often used to characterize and correct for
      geometric distortion of x-ray image intensifiers. For quantitative applications
      the number of BBs required for accurate distortion correction is prohibitively
      large for manual detection. A method to automatically determine the BB
      coordinates is described. The technique consists of image segmentation, pixel
      coalescing and centroid calculation. The dependence of calculated BB coordinates
      on segmentation threshold was also evaluated and found to be within the
      uncertainty of measurement.

PMID- 9755955
TI  - The practical implementation of a scatter model for portal imaging at 10 MV.
AB  - A detailed validation of a physical model for scattered radiation in portal
      images at 10 MV is presented. The ratio of the signal due to scattered radiation
      to the signal due to primary radiation (SPR) in an electronic portal image is
      defined. A simple physical model for SPR on the central axis (SPR*) was presented
      by Swindell and Evans for 6 MV and validated for field sizes up to 320 cm2. In
      this paper, the model is extended to 10 MV and validated for field sizes up to
      625 cm2. The model is first compared with Monte Carlo modelled data for field
      areas A from 40 to 320 cm2, scatterer thicknesses d of 5 to 35 cm water and
      scatterer to detector distances L2 of 40 to 100 cm. The physical model has one
      free parameter, which is fitted empirically using these data. Second,
      experimental measurements are performed with A from 40 to 625 cm2, d from 4.6 to
      27.4 cm and L2 fixed at 100 cm. The root mean square (rms) difference between the
      physical model and the Monte Carlo calculations was less than 0.001 for all L2
      greater than 60 cm. Agreement between experimentally measured and physically
      modelled data amounts to a radiological thickness error of at best 0.7 mm in
      273.6 mm and at worst 0.4 in 45.6 mm. The model performs equally well at all
      field sizes tested. This study shows that the Swindell and Evans SPR* model is
      accurate at 10 MV for L2 greater than 60 cm for all A up to 625 cm2.

PMID- 9755956
TI  - Influence of background correction in the estimation of myocardial uptake of
      99mTc labelled perfusion imaging agents.
AB  - The effects of different corrections for background activity in the estimation of
      low organ uptake of radiopharmaceuticals have been examined using myocardial
      perfusion imaging agents. Estimates of myocardial uptake of 99mTc-labelled MIBI
      and tetrofosmin were made both at rest and after exercise. Patients were given
      one or other of the agents (12 MIBI; 17 tetrofosmin) and the measurements at rest
      and after exercise were made within a week of each other using a planar gamma
      camera method incorporating an attenuation-corrected, geometric mean technique.
      Myocardial uptakes were estimated using two different background corrections and
      also with no background subtraction. Mean values were in the range 1.3 to 3.0%
      and showed that, for both agents, uptakes estimated with and without background
      correction could differ by a factor of two. Although the study was not designed
      to compare myocardial uptakes of the two agents, a background correction which
      accounted separately for activity in tissue over- and under-lying the heart
      resulted in similar mean values for tetrofosmin (1.7% both at rest and after
      exercise) and for MIBI (1.8% rest; 1.9% exercise). For both agents, no
      significant difference was observed between myocardial uptakes at rest and after
      exercise measured at about two hours post-injection.

PMID- 9755957
TI  - Tuberculosis among the disadvantaged. Proceedings of the 3rd annual meeting of
      the International Union Against Tuberculosis and Lung Disease, North American
      Region. Vancouver, British Columbia, Canada. 26-28 February 1998. Dedicated to
      the memory of Professor Stefan Grzybowski.

PMID- 9755958
TI  - The challenge of eradication: lessons from past eradication campaigns.

PMID- 9755959
TI  - Expanding the WHO tuberculosis control strategy: rethinking the role of active
      case-finding.

PMID- 9755960
TI  - Tuberculosis in Aboriginals in Canada.

PMID- 9755961
TI  - Aboriginal health: not just tuberculosis.

PMID- 9755962
TI  - Tuberculosis control among Alaska Native people.

PMID- 9755963
TI  - Tuberculosis among the foreign born in Massachusetts, 1982-1994: a reflection of
      social and economic disadvantage.

PMID- 9755964
TI  - Tuberculosis among the inner city poor.

PMID- 9755965
TI  - Case management of tuberculosis in New York City.

PMID- 9755966
TI  - Case management: a nursing point of view.

PMID- 9755967
TI  - Tuberculosis control in prisons.

PMID- 9755968
TI  - Tuberculosis among elderly persons, as observed among nursing home residents.

PMID- 9755969
TI  - Lung health and the environment in developing countries.

PMID- 9755970
TI  - Principles and priorities in acute respiratory infections in children.

PMID- 9755971
TI  - Tuberculosis control in refugees--policy and practices.

PMID- 9755972
TI  - Tuberculosis in refugees and displaced persons.

PMID- 9755973
TI  - Tuberculosis in health care workers: a multicentre Canadian prevalence survey:
      preliminary results. Canadian Collaborative Group in Nosocomial Transmission of
      Tuberculosis.

PMID- 9755974
TI  - The role of masks in preventing nosocomial transmission of tuberculosis.

PMID- 9755975
TI  - The role of ventilation in preventing nosocomial transmission of tuberculosis.

PMID- 9755976
TI  - Reducing the impact of tuberculosis transmission in institutions: beyond
      infection control measures.

PMID- 9755977
TI  - Scientific advances necessary for tuberculosis control.

PMID- 9755978
TI  - Prognostic determinants in extrahepatic bile duct cancer.
AB  - BACKGROUND/AIMS: The understanding of histopathological prognostic factors is
      critical to improving surgical outcome. This study investigated the microscopic
      features of cancer of the extrahepatic bile duct in order to clarify the
      prognostic determinants affecting surgical outcome. METHODOLOGY: In 90 cancers of
      the extrahepatic bile duct, the correlation between several microscopic
      parameters and survival was investigated. Lymphatic, venous, and perineural
      invasion, and the surgical margin (tumor-free or tumor-positive) were examined
      with serial step-wise sectioned specimens. RESULTS: Seven pT1-tumors showed no
      venous or perineural invasion and no lymph node involvement and were associated
      with prolonged survival (5 year survival, 86%) compared with pT2,3 tumors (23%).
      In pT2,3 tumors, lymphatic, venous, and perineural invasion was found in 80%,
      47%, and 88%, respectively, with no significant differences in occurrence of
      these parameters according to the origin of the primary tumor. As for survival
      with pT2,3 tumors, lymph node involvement (58%) and status of the surgical margin
      were significant parameters (p=.0330 and p=.0309, respectively). In addition,
      these latter parameters differed significantly according to the origin of the
      primary tumor. CONCLUSION: In cancer of the extrahepatic bile duct, lymph node
      involvement and status of the surgical margin were the most important microscopic
      parameters affecting prognosis.

PMID- 9755979
TI  - Difficult bile duct stone recurrence after endoscopy and extracorporeal shockwave
      lithotripsy.
AB  - BACKGROUND/AIMS: In a prospective study, we investigated stone recurrence in high
      risk patients with difficult common bile duct stones treated with extracorporeal
      shockwave lithotripsy (ESWL) after futile endoscopic attempts at stone extraction
      with sphincterotomy. METHODOLOGY: Endoscopic stone extraction proved unsuccessful
      in 35 of 659 patients presenting with common bile duct stones (5.5%, 11 males and
      24 females: mean age 71.0+/-10.0 yrs; BMI 25.8+/-3.9; ASA-Classification 2.63+/
      0.65), due to large stone size (10 patients), incarcerated stones (15 patients),
      stones inaccessible to the Dormia basket (7 patients) or an impacted Dormia
      basket (3 patients). The stones were localized radiologically. ESWL was performed
      using the HM3 lithotripter (Dornier, Munich/FRG). RESULTS: Immediately following
      ESWL, 17.1% of the patients treated showed complete stone clearance. In an
      additional 57.1%, further endoscopic stone extraction was required to achieve
      complete stone clearance, while 20.0% were discharged with small residual stone
      fragments. The remaining 2 patients (5.7%) required surgical intervention. Thirty
      four of 35 patients (97.1%) were followed-up for an average of 27+/-11 months.
      Five patients (14.3%) experienced stone recurrence at an average of 13.8+/-5.7
      months post ESWL. CONCLUSIONS: ESWL is a useful and safe adjunct to endoscopic
      management of difficult common bile duct stones in older, high-risk patients. The
      stone recurrence rate was about 14% after one year. All recurrent stones were
      treatable by endoscopy.

PMID- 9755980
TI  - The role of juxtapapillary duodenal diverticulum in the formation of gallbladder
      stones.
AB  - BACKGROUND/AIMS: Juxtapapillary diverticula (JPD) are considered to be associated
      with choledocholithiasis but not with cholecystolithiasis. However, there have
      been few comparative studies on the relationship between JPD and
      cholecystolithiasis under strict matching for sex and age. METHODOLOGY: Among
      4542 consecutive ERCPs at Tokyo Metropolitan Komagome Hospital, 549 patients who
      were 63 years of age or older were enrolled in this study and were matched for
      sex and age. They were divided into two groups: with and without JPD. Firstly,
      the frequency of cholecystolithiasis was compared between the two groups. Next,
      we recruited 83 patients whose JPD size could be measured by the ERCP films and
      investigated the relationship between JPD size and gallstones. RESULTS: We found
      no correlation between JPD and the overall frequency of cholecystolithiasis.
      However, an analysis of 83 patients with measurable JPD revealed that the size of
      JPD was closely linked to the occurrence of cholecystolithiasis. The JPD size was
      statistically larger in patients with cholecystolithiasis than those without.
      Moreover, when the mean diameter of JPD was 20 mm or more, the incidence of
      cholecystolithiasis rose up to 73.3%, which was significantly greater compared to
      the incidence in patients without JPD (p< 0.05). CONCLUSION: A larger JPD may
      play a role in the formation of gallbladder stones.

PMID- 9755981
TI  - Concurrent primary carcinoma of the gallbladder and acute cholecystitis.
AB  - BACKGROUND/AIMS: Primary carcinoma of the gallbladder is rare and associated with
      a late diagnosis and poor prognosis. Concurrent acute cholecystitis frequently
      obscures the presence of carcinoma. The information regarding gallbladder
      carcinoma with acute cholecystitis is limited. In order to better understand the
      presentation of gallbladder carcinoma with acute cholecystitis, we
      retrospectively reviewed the data of patients with primary carcinoma of the
      gallbladder. METHODOLOGY: The data of 86 patients with primary carcinoma of the
      gallbladder treated between 1979 and 1994 were compiled and reviewed. The
      patients were divided into 2 groups: Group 1 (with acute cholecystitis, 21
      patients) and Group 2 (without cholecystitis, 65 patients). Clinicopathological
      comparisons were made and evaluated between these two groups RESULTS: The average
      age of Group 1 patients was older than that of Group 2 patients (75+/-2 years vs.
      63+/-2 years; p<0.05). Three Group 1 patients presented with sepsis. The interval
      between the onset of symptoms and hospital admission in Group 2 patients was
      significantly (p<0.05) longer than that in Group 1 patients (243+/-95 days vs.
      20+/-11 days). Leukocytosis (>11,000/mm3) was more common in Group 1 patients
      than in Group 2 patients (47.6% vs. 15.4%). Jaundice was more common in Group 2,
      and fever was common in Group 1. The majority of Group 2 gallbladder cancers were
      stage V (75.4%). In contrast, 52.4% of Group 1 gallbladder cancers were stage III
      and 38.1% were stage V. The 30-day postoperative mortality rate in Group 1 and
      Group 2 patients was 9.5% and 7.7%, respectively. The cumulative survival of
      Group 1 patients was not different from that of Group 2 patients (log-rank test,
      p>0.05). CONCLUSIONS: Age, the interval of symptoms prior to admission, the
      location of abdominal pain, fever, leukocytosis, and the absence of jaundice
      suggested the presence of acute cholecystitis in gallbladder carcinoma. A high
      index of suspicion of the disease, intraoperative examination of gallbladder
      specimens, and more aggressive surgical treatment may improve patient survival.

PMID- 9755982
TI  - Gallbladder cancer with intratumoral anechoic foci: a mimic of adenomyomatosis.
AB  - We report a case of advanced gallbladder cancer in a 58-year-old man. On
      ultrasonography, there were anechoic foci within the tumor. Although anechoic
      foci within a thickened gallbladder wall usually represent intramural diverticula
      (dilated Rokitansky-Aschoff sinuses) of adenomyomatosis, cystically dilated
      cancerous glands were the etiology of these foci in this case. Thus, gallbladder
      cancer may also have anechoic foci within the tumor.

PMID- 9755983
TI  - Cutaneous metastatic adenocarcinoma of gallbladder origin: report of a case and
      review of the literature.
AB  - In the English literature, there have only been seven reports of metastasis from
      cancer of the gallbladder to the skin. This is the report of a 75-year-old woman
      who developed cutaneous metastasis from an adenocarcinoma of the gallbladder
      which was confirmed histologically. We report the uncommon metastatic potential
      of gallbladder carcinoma to the skin.

PMID- 9755984
TI  - Ascariasis of the alimentary tract, liver, pancreas and biliary system: its
      diagnosis by ultrasonography.
AB  - BACKGROUND/AIMS: The purpose of this study was to describe the echographic
      features of Ascaris lumbricoides invasion of the alimentary tract, biliary
      system, liver and pancreas. METHODOLOGY: We studied 38 patients with roundworm
      heavy infection whose diagnosis were primarily supported by ultrasonographic
      examination. RESULTS: Thirty-seven patients were admitted with the following
      clinical complications: bowel obstruction, intra and extrahepatic dilatation,
      acute cholecystitis, intrahepatic abscess, acute appendicitis, subphrenic
      collection and acute pancreatitis. Ultrasound scanning was able to recognize in
      30 cases the echogenic, nonshadowing images of the worms as single or multiple
      strips; in 8 cases, coiled structures and amorphous material were detected. The
      "inner tube" sign was considered as the most specific one. In two cases the
      roundworms were displayed within the stomach, a curious finding, up to now never
      reported in medical literature. CONCLUSIONS: Real-time sonography represents an
      efficient, reliable and non-invasive diagnostic approach for hepatobiliary,
      enteric and pancreatic ascariasis.

PMID- 9755985
TI  - Endoscopic ultrasonography in the evaluation of leiomyoma and extramucosal cysts
      of the esophagus.
AB  - BACKGROUND/AIMS: Leiomyoma is the most common type of benign esophageal tumor,
      whereas extramucosal cysts of the esophagus are congenital anomalies frequently
      asymptomatic in the adult and in most cases detected incidentally on chest x-ray.
      It is worthwhile considering these conditions together, because they present
      similar diagnostic and surgical problems. Conventional imaging tests do not lead
      to a precise diagnosis. The purpose of this study was to evaluate the use of
      endoscopic ultrasonography in the diagnosis of, and planning of treatment
      modalities for, these conditions. METHODOLOGY: Fifteen patients with esophageal
      leiomyoma and seven patients with extramucosal esophageal cysts were studied with
      endoscopic ultrasonography using an Olympus GF- EU-M3 instrument with a 7.5-12
      MHz echoprobe. In all patients, the results of endoscopic ultrasonography were
      compared with the histology of the resected specimens. RESULTS: The histology of
      the resected specimens confirmed the endosonographic diagnosis in all patients.
      No malignancy was found in any specimen. CONCLUSIONS: Endoscopic ultrasonography
      is very accurate in visualizing these lesions and differentiating cystic from
      solid submucosal esophageal masses; in addition, the test can establish the exact
      location of the mass in relation to the esophageal wall and mediastinum.
      Therefore, endoscopic ultrasonography has a great impact in confirming the
      diagnosis of leiomyoma and extramucosal cysts of the esophagus and facilitates
      therapeutic decision-making because of its capacity to clearly define the size,
      layer of the origin, and pattern of the mass.

PMID- 9755986
TI  - An immunohistochemical study of E-cadherin expression with correlations to
      clinicopathological features in gastric cancer.
AB  - BACKGROUND/AIMS: Reduced expression of E-cadherin leading to loss of cellular
      adhesion is crucial for cancer invasion and metastasis. The aim of this study is
      to investigate the role of E-cadherin in gastric tumorigenesis. METHODOLOGY:
      Immunohistochemical expression of E-cadherin was analyzed and correlated with
      clinicopathological characteristics of 122 patients with gastric cancer. RESULTS:
      Reduced E-cadherin expression was noted in 71 tumors (58.2%), while all normal
      epithelium showed a normal expression. Correlation of E-cadherin status to
      histological subtypes and growth patterns revealed a significantly higher
      frequency of reduced expression in diffuse type (46/60, 76.7%), advanced tumors
      (48/68, 70.6%) and stage III/IV (39/53, 73.6%) than that in intestinal type
      (25/62, 40.3%, p<0.0001), early tumors (23/54, 42.6%, p<0.005) and stage I/II
      (32/69, 46.4%, p<0.005) respectively. Moreover, abnormal expression was more
      frequent in tumors with positive lymph node metastasis (45/62, 72.6%), peritoneum
      seeding (10/11, 90.9%) and venous permeation (27/37, 73%) than that in tumors
      without lymph node metastasis (26/60, 43.3%, p<0.005), peritoneum seeding
      (61/111, 55.0%, p<0.05) and venous permeation (44/85, 51.8%, p<0.05). There is no
      statistical difference between E-cadherin expression and the status of perineural
      invasion or H. pylori infection. Analysis of survival for patients demonstrated
      that reduced E-cadherin expression was correlated with poor prognosis.
      CONCLUSIONS: These data indicate that impaired expression of E-cadherin is an
      important characteristic of gastric cancer and contributes to histogenesis, tumor
      growth, metastasis and poor survival.

PMID- 9755987
TI  - A new preoperative immunochemotherapy for the treatment of locally advanced
      esophageal cancer.
AB  - A promising preoperative immunochemotherapy regimen for locally advanced
      esophageal cancer is herein described. A 67-year-old man suffering from severe
      dysphagia was diagnosed with unresectable esophageal cancer at initial
      examination because of a tumor of 11 cm in length and suspicion of trachea
      invasion. Neoadjuvant immunochemotherapy was undertaken for the down-staging.
      Interleukin-2 (IL-2) (3.5 x 10(5) Japan reference units), nedaplatin (7 mg/m2)
      and 5-FU (300 mg/m2) were administered intravenously daily for 5 days a week for
      three weeks. The gross findings of a barium esophagogram and esophagoscopy
      revealed significant tumor regression in both size and shape. The patient
      underwent an esophagectomy through a laparotomy followed by a right thoracotomy.
      The surgical specimens were serially sectioned and examined microscopically. All
      of the surgical margins were clear (upper and lower margins as well as the
      adventitia), and there was no evidence of lymph node metastasis. The surgical
      specimen revealed neoplastic squamous ghost cells surrounding significant
      lymphocyte infiltration. This appears to be a unique feature of this particular
      neoadjuvant immunochemotherapy.

PMID- 9755988
TI  - Two cases of gall bladder agenesis and review of the literature.
AB  - Two patients with agenesis of the gall bladder are reported herein, and the
      relevant literature reviewed. It is important to be aware of this condition as
      patients often present with symptoms of gall bladder disease, which may lead to
      confusion at laparoscopic cholecystectomy.

PMID- 9755989
TI  - The relation between irregular bowel movement and the lifestyle of working women.
AB  - BACKGROUND/AIMS: It is said that constipation is related to the occurrence and
      increase of bowel disease and colon cancer; however, there are few reports on
      this subject, and information about bowel movements in connection with the
      lifestyles of working women are almost non-existent. METHODOLOGY: We conducted a
      survey of working women and obtained 509 valid responses. The odds ratios of the
      following factors were calculated: the number of bowel movements, skipping
      breakfast, dieting, suppressing bowel movements, haemorrhoids (anal fistulae),
      and stress. RESULTS: The prevention of skipping breakfast and suppressing bowel
      movement had a big effect on the increase of bowel movements and in preventing
      constipation, especially when the two factors were combined. For those
      experiencing haemorrhoids, stress had a great influence. More than half of the
      respondents admitted that the first appearance of the signs of constipation was
      during their high school days or before. The peculiar sense of shame of women in
      their adolescence, the disorder of daily life, the desire to obtain a slim figure
      and stress are thought to be triggers for the problem of constipation.
      CONCLUSIONS: It is clear that the four factors in daily life defined above can
      have significant influence on constipation in women. It is thought that a proper
      diet with the right guidance, as well as social considerations can have
      favourable effects on these factors.

PMID- 9755990
TI  - Surgery for ulcerative colitis in Greece: clinicoepidemiological features and
      long-term outcome of 69 consecutive patients.
AB  - BACKGROUND/AIMS: In this study, the various clinicoepidemiological
      characteristics and long-term follow-up of patients operated on for ulcerative
      colitis in Greece over a period of 15 years, are reviewed. METHODOLOGY: A total
      number of 69 out of 413 patients with ulcerative colitis (17.8%) seen and
      followed-up for a mean period of 12 years, had undergone ileorectal anastomosis
      (45.6%), total proctocolectomy with permanent ileostomy (35.6%), ileal-anal pouch
      anastomosis (17.6%) and Kock ileostomy (1.5%), mainly for bad response to
      conservative treatment (78.3%). Other causes for operation were large bowel
      cancer (8.7%), profound hemorrhage (4.3%), toxic megacolon (1.4%), and
      rectovaginal fistula (1.4%). Almost half of the operations (45%) were performed
      between the first and fourth year after the establishment of diagnosis. RESULTS:
      A number of statistically highly significant differences between the operated and
      non-operated group of patients were noticed. So, patients operated on had more
      extensive disease in comparison with non-operated ones and were younger at the
      time of diagnosis. The overall perioperative morbidity and mortality were 6% and
      5% respectively. Survival was not statistically significantly different between
      operated and non-operated patients and also did not differ significantly between
      men and women. Most of the deaths in the operated and non-operated group of
      patients were unrelated to ulcerative colitis. CONCLUSION: It is concluded that
      the clinicoepidemiological features and outcome of the Greek patients operated on
      for ulcerative colitis have similarities with those reported from other developed
      countries of the world.

PMID- 9755991
TI  - Circular hemorrhoidectomy in advanced hemorrhoidal disease.
AB  - BACKGROUND/AIMS: Milligan-Morgan's hemorrhoidectomy has a high recurrence rate (>
      10%) in patients with circular IV grade hemorrhoids. In such cases a circular
      hemorrhoidectomy with complete elimination of residual piles, and anoplasty might
      be more successful. The aim of this retrospective study was to compare the
      results of circular hemorrhoidectomy using the Hopital Leopold Bellan (HLB)
      technique (Paris) with the reported results of other techniques in patients with
      advanced hemorrhoidal disease. METHODOLOGY: From January 87 to December 96, 100
      consecutive patients with circular IV grade hemorrhoids underwent radical
      hemorrhoidectomy. Mean hospital stay was 4 days (range 3-7). Patients were
      strictly controlled in the postoperative period and in cases of early fibrosis
      anal dilators were used. RESULTS: Eighty one percent of patients had a complete
      recovery. The recurrence rate was 4%. The cumulative rate of early and late
      complications was 34%. Early and late hemorrhages were more frequent than in
      traditional hemorrhoidectomy, while the incidence of anal stenosis was the same.
      CONCLUSIONS: The HLB operation is the best choice for patients with advanced
      circular hemorrhoids because of its radicality and good results. The
      postoperative morbidity of HLB hemorrhoidectomy is higher than traditional
      hemorrhoidectomy; nevertheless, all complications are tractable without extension
      of hospital stay.

PMID- 9755993
TI  - Surgery in Crohn's disease: when, where and why the recurrences?
AB  - One frustrating feature in the surgical management of Crohn's disease is the high
      recurrence rate which may lead to reoperation. It is common opinion that relapses
      occur haphazardly both in time and in site, and the causes remain unknown. When
      does a recurrence really arise after surgery? Is the site of recurrence
      determined by definite causes? Is there a relapsing factor? Between 1965 and
      1995, 177 patients underwent surgery for Crohn's disease. The procedures
      performed in 145 cases were those popular at the time, while a recent series of
      20 selected patients was managed following a new approach based on
      epiploonplasty. This strategy stems from the strong conviction that Crohn's
      disease is not a primary bowel disease but the result of stasis and superimposed
      infection due to a primary hemolymphatic disorder of the mesentery. The five-year
      recurrence rate was 62% in patients operated on according to standard procedures,
      while no recurrences were reported in the epiploonplasty group. Among 12
      remaining patients with recurrent disease, two cases are reported in detail
      because they provide evidence in favor of the hemolymphatic theory. This study
      also maintains that recurrences, viewed with the hemolymphatic disorder in mind,
      occur immediately after surgery, while the superimposed intestinal inflammatory
      process and stricturing events may appear clinically at different time intervals
      during follow-up. The site of recurrences usually corresponds to the mesenteric
      region subjected to compression. Altered mesenteric microcirculation appears to
      be the true essence of the disease.

PMID- 9755992
TI  - Retroperitoneal fibrosis: unusual localization.
AB  - Six cases of retroperitoneal fibrosis, each with a different pathogenesis and
      unusual localization were observed from 1980 to 1996. Four patients had had
      previous surgery for a neoplasm, one patient had idiopathic retroperitoneal
      fibrosis, and the last patient was hardly classifiable due to the complexity of
      the clinical pattern. The mean survival in 3 patients with malignant
      retroperitoneal fibrosis was 7 months. Two patients treated with medical therapy
      are still alive and in good clinical condition. The aspecificity of the symptoms
      makes early diagnosis difficult. CT and NMR are essential procedures for
      differential diagnosis of abdominal masses. Histology differentiates benign from
      malignant retroperitoneal fibrosis. The choice between medical or surgical
      therapy depends on the general condition of each patient.

PMID- 9755994
TI  - Gamma-glutamyl transferase, intestinal alkaline phosphatase and beta
      hexosaminidase activity in duodenal biopsies from chronic alcoholics.
AB  - BACKGROUND/AIMS: Gamma-glutamyl transferase (GGT) and intestinal alkaline
      phosphatase (IAP) are present in the brush border of mucosal absorptive cells in
      the small intestine. There are few studies on the effect of alcohol consumption
      on these enzymes. Increased intestinal GGT in biopsy specimens from the duodenum
      has been described in chronic alcoholics. In experimental animals alcohol effects
      varies with duration of exposure and with nutritional factors. METHODOLOGY: IAP,
      GGT and the lysosomal enzyme beta-hexosaminidase (Hex) were examined in duodenal
      biopsy specimens from 23 defined chronic alcoholics and 33 non alcoholic
      controls. The results were correlated to serum GGT, alkaline phosphatase, CDT
      (Carbohydrate Deficient Transferrin) and the villus index. RESULTS: Both the
      intestinal GGT (0.52 + 0.05 SEM vs. 0.30 + 0.024 SEM microkat/g protein,
      p<0.0001) and the IAP (22.11 + 2.49 SEM vs. 12.28 + 1.35 SEM microkat/g protein,
      p=0.0010) were significantly higher in alcoholics than in controls. There was no
      correlation between intestinal and serum alkaline phosphatase and GGT activity
      within the two groups. CONCLUSIONS: Chronic alcohol consumption causes increased
      intestinal GGT and IAP activity in man. No effect on Hex was seen. The enzyme
      activity in the small intestine did not correlate to serum enzyme activity or to
      morphological changes in the small intestine.

PMID- 9755995
TI  - Continuous maintenance with low-dose lansoprazole versus Helicobacter pylori
      eradication in the prevention of duodenal ulcer recurrence.
AB  - BACKGROUND/AIMS: Reduction of gastric acid secretion by maintenance treatment
      with antisecretory agents and eradication of H. pylori by antibiotics constitute
      the most effective therapeutic options in preventing duodenal ulcer relapse. The
      aim of this study was to compare the effect of a 12-month low-dose lansoprazole
      maintenance treatment with H. pylori eradication on the rate of ulcer relapse in
      H. pylori-positive duodenal ulcer patients. METHODOLOGY: After a healing phase
      with lansoprazole 30 mg/die or lansoprazole 30-60 mg/die plus antibiotics
      (amoxycillin, tinidazole and colloidal bismuth subcitrate), 84 patients with
      healed duodenal ulcer entered the follow-up phase. Thirty-eight patients with
      persistent H. pylori infection received lansoprazole 15 mg at bedtime, whereas 46
      in whom H. pylori was eradicated during the acute phase received no active
      therapy during the 12-month follow-up. The two groups were well balanced
      concerning all demographic characteristics. Clinical controls were performed
      every 3 months or sooner in the event of symptomatic relapse. RESULTS: In terms
      of per protocol analysis, the overall rate of ulcer relapse at 6 months was 5.5%
      (2/36) in the maintenance group and 0 (0/42) in the antibiotic group. The
      corresponding figures at 12 months were 20.5% (7/34) and 5.7% (2/35),
      respectively (p:ns, 95% CI for the difference -0.30+0.02). On intent to treat
      analysis, the rate of ulcer relapse at 6 months was 5.2% (2/38) in the first
      group and 0% (0/46) in the second group: at 12 months the corresponding figures
      were 19.4% (7/36) and 4.3% (2/46), respectively (p=0.06; CI 95%: +0.016+0.28). No
      significant side effects were observed during long-term maintenance with
      lansoprazole. CONCLUSIONS: Continuous maintenance with low-dose lansoprazole may
      constitute a valuable alternative to H. pylori eradication for the prevention of
      relapse and complications in duodenal ulcer patients not suitable for, or who
      have failed, H. pylori eradication.

PMID- 9755997
TI  - The effects of omeprazole, a proton pump inhibitor, on early gastric stagnation
      after a pylorus-preserving pancreaticoduodenectomy: results of a randomized
      study.
AB  - BACKGROUND/AIMS: To determine the effects of Omeprazole, a proton pump inhibitor
      (PPI), on gastric stasis following a pylorus-preserving pancreatico-duodenectomy
      (PPPD) by means of a randomized trial of PPPD patients. METHODOLOGY: Forty-two
      PPPD patients were randomly divided into two groups: Group 1 (n=24) received a
      PPI through a jejunal tube after PPPD, whereas Group 2 (n=18), serving as
      controls, received a saline solution through a jejunal tube and no medication
      after a PPPD. The daily volume and total acidity of the gastric juice, aspirated
      via nasogastric tube, were measured each day for 7 days following PPPD. RESULTS:
      In Group 1 the mean daily aspirated volume of gastric juice was 160.2 ml, and the
      mean maximum volume was 222.8 ml on the first postoperative day. In Group 2, six
      patients were withdrawn from this study for therapy on the third or fourth
      postoperative day due to gastric bleeding and/or a large amount of excreted
      gastric juice (in excess of 2,000 ml). The mean daily aspirated volume of gastric
      juice in the remaining Group 2 patients was 787.4 ml, and the mean maximum volume
      was 1,039 ml on the third postoperative day. Gastric secretion was significantly
      lower in Group 1 (p<0.05). Further, the total acidity of the gastric juice was
      significantly lower in Group 1 than in Group 2 for each of the 7 postoperative
      days (p<0.05). CONCLUSIONS: These results indicate that postoperative
      administration of a PPI significantly suppresses the volume and acidity of the
      gastric juice after PPPD.

PMID- 9755996
TI  - Prognostic relevance of histomorphological parameters and DNA content and their
      therapeutic consequences in esophageal carcinoma: a multivariate approach.
AB  - BACKGROUND/AIMS: Despite recent advances in surgical and multidisciplinary
      treatment, the prognosis for patients with esophageal carcinoma remains poor. The
      low prognostic accuracy of even surgical pathological TNM staging suggests that
      additional parameters would be useful in determining the prognosis. METHODOLOGY:
      We undertook a retrospective analysis of 115 patients who had undergone
      transhiatal and transthoracic esophageal resection due to squamous cell carcinoma
      of the esophagus. In addition to TNM classification and the usual morphological
      criteria, a quantitative DNS analysis using Image DNA cytometry was performed. At
      the time of DNA analysis, histomorphological parameters and survival time was not
      known. RESULTS: The main prognostic parameter was the curativity (R
      classification) of the operation. Using only patients who had had R0 resection, a
      multivariate analysis was performed. Parameters included: patient age;
      preoperative ASA classification; tumor localization; pN category; number of intra
      thoracal lymph nodes removed; pT category; pM category; grading; lymphangiosis;
      ploidy; operative procedure, and the development of postoperative complications
      identifying the ploidy, and the depth of tumor infiltration of prognostically
      independent factors. CONCLUSIONS: In the case of a diploid or tetraploid DNA
      content, tumor resection is recommended even in the case of lymph node metastasis
      at the truncus coeliacus. Patients with a diploid or tetraploid tumor without
      distant metastasis and tumor stage pT1-pT3 may, after curative (RO) transthoracic
      resection with two-field lymph node dissection, have an advantage over patients
      having a transmediastinal procedure in terms of long-term follow up. In cases of
      aneuploid DNA content, tumor resection shows no advantage over palliative non
      operative procedures. Preoperative radio- or chemotherapy may improve the
      prognosis of these patients.

PMID- 9755998
TI  - Blood transfusion and postoperative serum interleukin-6 levels in colorectal
      cancer patients.
AB  - BACKGROUND/AIMS: Postoperative cytokine response affects various factors.
      However, excessive stress responses are deleterious as increased serum
      concentration of cytokines may induce tissue injury and an impaired immune
      system. METHODOLOGY: We determined serum IL-6 levels in 35 patients who had
      undergone resection of colorectal carcinoma. Eleven patients had a blood
      transfusion before or during the operation (transfused group) but 24 patients had
      received no blood transfusion (control group). Serum IL-6 levels were determined
      before the operation, and at the end of operation,POD-1, 3, and 7. RESULTS: There
      was no significant difference of preoperative mean levels of IL-6 between these
      two groups (p=0.20). Postoperative serum IL-6 levels were significantly elevated.
      Mean serum levels of IL-6 were significantly higher at the end of operation in
      the transfused group than in the control group (131.7 pg/ml in control group and
      269.8 pg/ml in transfused group; p=0.02). CONCLUSION: The present study suggested
      that perioperative allogeneic blood transfusion can induce an excessive cytokine
      response and may be deleterious.

PMID- 9755999
TI  - Mini-laparoscopic cholecystectomy.
AB  - BACKGROUND/AIMS: The authors describe their experience in performing
      cholecystectomy using mini-laparoscopy in selected cases of uncomplicated
      cholelithiasis. This involved making one 10 mm, one 5 mm and two 2 mm incisions.
      METHODOLOGY: From July 1996 to August 1997, 60 cholecystectomies were performed
      using mini-laparoscopy, out of a total of 203 video-laparocholecystectomies
      performed during the same period. RESULTS: Average length of the operations was
      36 minutes from insertion of the first trocar to extraction of the gallbladder.
      All patients were discharged in the second day after surgery. No short-term intra
      or post- operative complications occurred. CONCLUSIONS: The benefits of mini
      cholecystectomy are potential advantages in improved appearance, reduced pain,
      better respiratory function, fewer wall complications. Therefore, the authors
      believe that mini-laparoscopy should not be assessed in terms of percentage of
      use or success, but rather considered as a part of the laparoscopic method to be
      used in selected cases.

PMID- 9756000
TI  - Diagnosis of small intestinal bacterial overgrowth in clinical praxis: a
      comparison of the culture of small bowel aspirate, duodenal biopsies and gastric
      aspirate.
AB  - BACKGROUND/AIMS: This study was undertaken to validate the usefulness of the
      culture of duodenal biopsy specimens and gastric aspirate compared to the culture
      of small bowel aspirate for diagnosing small intestinal bacterial overgrowth. We
      also investigated the occurrence of predisposing conditions in these patients.
      METHODOLOGY: Seventy five consecutive patients, admitted because of symptoms
      which caused us to suspect small intestinal bacterial overgrowth, were studied.
      For all patients, specimens for the culture of small bowel aspirate, duodenal
      biopsies and gastric aspirate were obtained during upper endoscopy. RESULTS:
      Eighteen patients showed growth of gram negative bacteria, 22 growth of gram
      positive bacteria and 35 showed no significant growth in cultures of small bowel
      aspirate. Cultures of duodenal biopsies revealed gram negative bacteria in 11
      patients, gram positive bacteria in 9 and no growth in 55. Cultures of gastric
      aspirate revealed gram negative bacteria in 7 patients, gram positive bacteria in
      12 and no growth in 51. Ten of the 18 patients with gram negative overgrowth and
      13 of the 22 patients with gram positive overgrowth had a predisposing condition.
      In contrast, only 4 of the 35 without overgrowth had a predisposing condition.
      CONCLUSIONS: The culture of duodenal biopsy specimens or gastric aspirate is a
      less sensitive method than the culture of small bowel aspirate. Most patients
      with culture-proven small intestinal bacterial overgrowth had at least one
      predisposing condition.

PMID- 9756001
TI  - Effect of clonidine on gastrointestinal transit time.
AB  - BACKGROUND/AIMS: Orocecal time can be measured by lactulose H2 breath test.
      Duodenal entry time can be evaluated by measuring D-xylose; the duodeno-cecal
      time can be derived by subtracting duodenal entry time from orocecal time. In
      this study we established the normal value of these parameters for our laboratory
      in males and also evaluated the effect of clonidine on these parameters.
      METHODOLOGY: In 9 healthy male volunteers orocecal time was measured by the
      lactulose H2 breath test. Duodenal entry time was established by measuring blood
      D-xylose. Duodenocecal time was derived by subtracting duodenal entry time from
      orocecal time. RESULTS: The mean orocecal time was 54.44 + 3.77 minutes; the mean
      duodenal entry time was 17.22 + 3.15 minutes and the mean duodenocecal time was
      37.22 + 3.16 minutes. CONCLUSIONS: Oral clonidine prolonged orocecal, duodenal
      entry and duodenocecal times in only 33% of the subjects.

PMID- 9756002
TI  - Effects of intraoperative blood transfusion on postoperative complications and
      survival after orthotopic liver transplantation.
AB  - BACKGROUND/AIMS: Massive blood transfusion related to the coagulation disorders
      occurring during the anhepatic and reperfusion phases, remains a serious problem
      during orthotopic liver transplantation. To analyze the influence of
      intraoperative blood transfusion on postoperative complications, and survival and
      to identify the preoperative variables associated with greater intraoperative
      bleeding, 100 orthotopic liver transplantations, carried out on adults, were
      reviewed in our center. METHODOLOGY: Patients were grouped into three categories
      according to intraoperative blood volume transfused; group A, 1.5 or less blood
      volumes transfused; group B, > 1.5 and < 3 volumes used and group C, 3 or more
      volumes given. RESULTS: Group C patients had a higher incidence of upper
      abdominal surgery (p < 0.01 between groups C and A. and p<0.05 between groups C
      and B); higher values of postoperative total bilirubin and SGOT, and lower
      prothrombin activity. Acute rejection and steroid-resistant episodes per patient
      occurred less commonly (p <0.01 between groups C and A) and so did chronic
      rejection (p <0.05 between groups C and B). Higher infection rate, and
      gastrointestinal and intraabdominal complication rates were also noticed in
      groups C and B (p < 0.01 and p < 0.05 respectively). Patient survival rates were
      lower in group C (p < 0.05 between groups C and A). CONCLUSIONS: It was concluded
      that previous upper abdominal surgery was the only preoperative factor associated
      with massive blood transfusion. Poor graft function during the first days after
      transplant, higher incidence of infections, higher incidence of gastrointestinal
      and intraabdominal complications, and lower rejection episodes and survival for
      patients receiving intraoperatively large amounts of blood can be expected.

PMID- 9756003
TI  - Resectional liver surgery in metastatic liver disease.
AB  - BACKGROUND/AIMS: To increase resectability rate and decrease intra-hepatic
      recurrence of metastatic liver disease of patients suffering from secondary liver
      tumors. Metastatic liver disease remains challenging and life threatening. At the
      time of diagnosis only 10% of patients are amenable to liver resection and of
      those 60-70% will develop recurrence in the residual liver 16 to 24 months
      following liver resection METHODOLOGY: Seventy patients out of a total number of
      305 seen between November 1991 and May 1998, underwent combined liver resection
      followed by adjuvant locoregional targeted immunochemotherapy. Patients were
      divided in two groups. Group A (n=32) had uni-lobular localization of their
      disease and group B (n=38) had bi-lobular spread of the disease, but tumor
      occupied was less than 70% of liver surface. All had hepatic resection followed
      by adjuvant immuno-chemotherapy. RESULTS: Group A (n=32) had a 5 year survival of
      75% with 8 patients alive more than 6 years and a mean survival for alive and
      dead patients of 50 months. Group B (n=38) had a mean survival of 40 months with
      6 patients alive longer than 5 years. CONCLUSIONS: Liver resection combined with
      adjuvant immuno-chemotherapy enhances overall long-term survival in both patients
      with limited and advanced metastatic liver disease, and is recommended as a
      promising therapeutical alternative.

PMID- 9756004
TI  - Liver transplantation: problems and perspectives.
AB  - Orthotopic liver transplantation (OLT) has made remarkable advances. However,
      results vary according to the etiology and the severity of the liver disease.
      Shortage of donors is becoming an increasing problem because results are
      improving, more centers are embarking on transplantation and because the
      indications become wider. Measures have to be taken to improve the number of good
      donor livers and the condition of the recipient.

PMID- 9756005
TI  - The importance of initial daily administration of interferon alpha for the
      eradication of hepatitis C virus in patients with chronic hepatitis C: a
      multicenter randomized trial.
AB  - BACKGROUND/AIMS: We studied the effect of initial daily administration of
      interferon for the treatment of chronic hepatitis C, to clarify a more effective
      treatment protocol for the eradication of the hepatitis C virus. METHODOLOGY:
      Consecutive patients who met the inclusion criteria were randomly enrolled in two
      groups in this study. One hundred and five patients were randomized and assigned
      to two groups. Patients, who enrolled in group A, were treated with 6 million
      units of natural interferon-alpha given subcutaneously daily for an initial two
      weeks and then thrice a week for 22 weeks. Patients, who were enrolled in group
      B, were treated with the same dose of interferon-alpha given for 26 weeks thrice
      a week from the first administration. RESULTS: In groups A and B, 58 and 47
      patients were analyzed, respectively. At the end of treatment, 37 patients in
      group A (63.8%) had negative serum HCV-RNA test, compared with 26 in group B
      (55.3%), but at 6 months after discontinuation of interferon administration, 27
      patients in group A (46.6%), compared with 8 in group B (21.3%). The rate of
      complete remission in group A (46.6%) was higher than that in group B (21.3%)
      (P<0.01). In patients with genotype 1b virus, the rate of complete remission was
      higher in group A (31.3%) than in group B (12.5%) (not significantly), and the
      relapse rate was lower in group A (9.4%) than in group B (37.5%), significantly
      (p<0.05). CONCLUSIONS: This study suggests that initial daily interferon
      administration is necessary to gain a higher rate of serum HCV-RNA eradication in
      patients with chronic hepatitis C.

PMID- 9756006
TI  - Effects of matrix metalloproteinase inhibitor BB-94 on liver cancer growth and
      metastasis in a patient-like orthotopic model LCI-D20.
AB  - BACKGROUND/AIMS: The aim of this study was to try to understand the effects of
      the synthetic matrix metalloproteinase inhibitor Batimastat (BB-94) on
      hepatocellular carcinoma (HCC). METHODOLOGY: An orthotopic metastatic human
      hepatocellular carcinoma in nude mice model (LCI-D20) was used to study primary
      tumor growth, local invasion and metastasis of HCC. MTT assay was used to study
      the effects of BB-94 on cytotoxin and proliferation of HCC cell line SMMC-7721 in
      vitro. A gelatine zymograph was used to study the expression of MMPs in the LCI
      D20 tumor tissue. RESULTS: BB-94 can inhibit primary tumor growth, local
      invasion, intrahepatic and lung metastasis, as well as prolong survival. BB-94
      did not affect the proliferation of HCC cells in vitro. LCI-D20 tumor tissue
      expresses MMP-2 and MMP-9. CONCLUSIONS: BB-94 has a cytostatic therapeutic effect
      on HCC.

PMID- 9756007
TI  - Perihepatic lymphadenopathy: a marker of response to interferon alpha in chronic
      hepatitis C.
AB  - BACKGROUND/AIMS: Recently it was shown that perihepatic lymphadenopathy (PHL)
      correlates with histological activity in chronic hepatitis C. However, the
      question whether there is a correlation between the response to interferon alpha
      and PHL has not yet been raised. METHODOLOGY: We examined 103 patients who had
      been treated with interferon alpha for hepatitis C. Prior to treatment all
      patients had undergone high resolution ultrasonography. Thirty-six patients had
      follow up ultrasound scans during the course of the treatment. According to size
      and number of lymph nodes we introduced a grading of the PHL and determined grade
      I as minimal, grade II as medium and grade III as extensive PHL. RESULTS:
      Classification of PHL prior to treatment revealed 40 patients with PHL I, 30 with
      grade II and 33 with grade III. Hepatic inflammatory activity according to the
      Ishak score was increased in patients with PHL III (9.1+/-2.4) compared to PHL II
      (6.7+/-2.9) and PHL I (7.3+/-3.1) (p=0.01). In patients with PHL grade I prior to
      treatment 45% were initial responder, patients with grade II or III showed
      response rates of 40% and 33%, respectively. During therapy we found an increase
      of PHL in one out of 13 primary responder vs. 10 out of 23 non-responder
      (p=0.03). CONCLUSIONS: In conclusion, monitoring of PHL by abdominal
      ultrasonography is a simple, non-invasive and cheap additional marker of response
      to interferon alpha.

PMID- 9756008
TI  - Liver volume in patients with or without chronic liver diseases.
AB  - BACKGROUND/AIMS: The size of the liver is an important clinical parameter; the
      aim of this study is to examine the correlation between liver volume and etiology
      and the severity of disease, and to evaluate its usefulness in predicting
      survival. METHODOLOGY: Patients observed in this study were comprised of thirty
      three patients with non-liver disease and 44 patients with chronic liver disease
      (alcoholic hepatitis, 9; hepatitis B, 24; and hepatitis C, 11). The liver volume
      was measured from digitized CT scan images. Techniques of planimetry and
      summation of areas were utilized for calculation. RESULTS: The prediction model
      to estimate liver volume in patients without liver disease was: liver volume
      (ml)= [13 x height (cm)] +[12 x weight (Kg)] - 1530. The volume ratio (%)
      [(volume from reconstructed image /predicted volume) x 100] of alcoholic patients
      was 135.9+/-25.8, which was significantly higher than that of chronic hepatitis B
      (73.6+/-15.4) and chronic hepatitis C (74.5+/-20.7). Patients with chronic viral
      hepatitis were classified into Child-Pugh class A (N=10), B (N=14) and C (N=11).
      Analysis of variance and trend test revealed that the volume ratio had a
      significant decreasing trend from the control group (100.5+/-8.1), class A
      (83.4+/-13.9), class B (72.2+/-13.2) to class C (63.3+/-14.4). CONCLUSIONS: Liver
      volume can be predicted from patients' weight and height if they have no liver
      disease. The liver volume ratio correlates much better with etiology and severity
      of the disease and is a reliable predictor for patient's survival.

PMID- 9756009
TI  - Recovery of liver functions following surgical biliary decompression in
      obstructive jaundice.
AB  - BACKGROUND/AIMS: Derangement of liver functions in obstructive jaundice has been
      known to influence surgical outcome. The pattern and time frame of liver function
      recovery in patients with surgical obstructive jaundice undergoing a bilioenteric
      anastomosis has not been comprehensively defined in human beings. METHODOLOGY:
      Fifty patients of obstructive jaundice who underwent a bilioenteric anastomosis
      had their liver function evaluated done by biochemistry (pre-operatively and
      postoperatively on day 1,4,7 and 6 weeks) and radionuclide mebrofenin scan
      (preoperatively and 6 weeks postoperative). RESULTS: The results have shown a
      constant and significant decline in serum bilirubin levels by day 4 (p=0.04),
      however the decline in serum levels was not uniformly progressive in 54%
      patients. The decline in serum alkaline phosphatase levels has been constant and
      progressive reaching significant levels by day 4(p=0.01). Serum transaminases
      showed an initial rise followed by a rapid fall, again achieving significant
      levels by day 4 (p=0.003 & 0.009). Serum albumin decreased on day 1 itself but
      remained static after that. On isotope scanning hepatic uptake showed uniform
      improvement with 92% of patients having achieved a normal uptake after 6 weeks.
      Gastrointestinal excretion of the isotope however was still delayed in 26%
      patients at 6 weeks. Almost all these patients had an abnormal bilirubin level
      decline in the immediate postoperative period. CONCLUSIONS: Hepatic functional
      recovery has been seen to start immediately following bilioenteric anastomosis
      and has usually completed itself by 6 weeks. Patients who show an abnormal
      recovery pattern based on bilirubin levels need to be observed for a longer time.

PMID- 9756010
TI  - Zinc metabolism after transcatheter arterial embolization for hepatocellular
      carcinoma.
AB  - BACKGROUND/AIMS: Zinc metabolism after transcatheter arterial embolization (TAE)
      was studied in 15 cases of hepatocellular carcinoma (HCC) with liver cirrhosis
      (LC). METHODOLOGY: Serum zinc concentrations, 24-hr urinary excretion of zinc,
      blood ammonia (NH3) and plasma endotoxin (Et) levels were measured before and
      one, three and seven days after TAE. RESULTS: Serum zinc levels one day after TAE
      were decreased (p<0.05) as compared to those before TAE and then returned to
      pretreatment values three days or more after TAE. Urinary excretion of zinc
      increased (p<0.01) one day after TAE, but then returned to the pretreatment value
      three days after TAE. Although blood NH3 and plasma Et levels increased (P<0.05)
      the day after TAE, these parameters recovered on the third day. CONCLUSIONS:
      Decrease in the serum zinc concentration after TAE is considered to be due to
      changes in the zinc distribution in the body associated with endotoxemia, as well
      as increased urinary zinc excretion.

PMID- 9756011
TI  - Imaging of large early and early advanced hepatocellular carcinomas of more than
      5 cm in diameter: report of two cases.
AB  - In an attempt to clarify the imaging characteristics of large early and early
      advanced hepatocellular carcinoma (HCC), we present two such cases which were
      greater than 5 cm in diameter. One case had four early HCCs and the other had
      early advanced HCC which was followed for five years and nine months. Multiphasic
      CT, CT arteriography (CTA), CT arterial portography (CTAP), and MR imaging were
      performed. Early HCC was shown as a low density mass by multiphasic contrast CT,
      CTAP and as a hyperintense mass on a T1-weighted image (WI) and isointense on
      T2WI. Early advanced HCC was demonstrated as a hypodense mass with hyperenhancing
      interior nodules on CTA, and isodense with hypodense internal foci on CTAP. One
      follow-up case showed a multi-step progression from early to early advanced HCC,
      and finally to overtly advanced HCC. Despite the unusually large size of these
      two tumors, the findings of multiphasic CT, CTA, CTAP, and MR imaging were
      consistent with those seen in common-sized (less than 2 cm) early and early
      advanced HCCs. Multi-step progression of hepatocarcinogenesis was observed in one
      case.

PMID- 9756012
TI  - Asymptomatic glucagonoma presenting with an isolated hepatic nodule.
AB  - A 37-year-old male patient, without any particular symptoms apart from moderate
      right upper quadrant postprandial pain, was found to have a liver mass identified
      as a glucagon-producing tumor. Plasma glucagon levels were slightly increased,
      whereas those of other gut peptides were within the normal range. Despite an
      extensive pre- and intraoperative diagnostic work-up, a presumed primary
      glucagonoma remained undetected. This unusual presentation with the absence of
      any symptoms typical of glucagonoma, as well as the presence of histopathological
      features characteristic of both benign and malignant forms of glucagonoma, make
      this case very peculiar. A clinically silent, apparently unrelated adenocarcinoma
      of the left colon was also found. The concomitant presence of a glucagonoma and a
      carcinoma of the large intestine has not been previously reported, and its
      significance remains unclear.

PMID- 9756013
TI  - Needle track seeding following percutaneous ethanol injection for treatment of
      hepatocellular carcinoma.
AB  - We report two cases of needle track seeding in the subcutaneous tissue and
      intercostal muscles following percutaneous ethanol injection for the treatment of
      hepatocellular carcinoma. In one patient, tumor seeding was observed 11 months
      after a total of 12 alcohol injections, and in the other patient, tumor seeding
      was observed 30 months after a total of 18 alcohol injections. The cases reported
      in the literature are discussed.

PMID- 9756014
TI  - Hypoplasia of the left hepatic lobe associated with floating gallbladder: a case
      report.
AB  - Agenesis or hypoplasia of the hepatic lobe and floating gallbladder are both
      rare. We report an extremely rare case of hypoplasia of the left hepatic lobe
      accompanied by floating gallbladder. The patient was a 71-year-old woman, with no
      past history of related symptoms, who was admitted for further evaluation of
      postprandial epigastralgia, nausea, and diarrhea. Laboratory data on admission
      showed chronic liver disease with positive anti-hepatitis C virus antibody.
      Abdominal ultrasonography and computed tomography revealed the absence of the
      left hepatic lobe and displacement of the gallbladder to the left. On endoscopic
      retrograde cholangiography, the cystic duct originated from the right side of the
      bile duct, but the gallbladder was displaced to the left. Poor yolk-induced
      gallbladder contraction suggested the existence of hypotonic biliary dyskinesia.
      Angiography demonstrated no middle or left hepatic arteries, indicating
      congenital hypoplasia of the left hepatic lobe. Open cholecystectomy was carried
      out, and a diagnosis of hypoplasia of the left hepatic lobe accompanied by
      floating gallbladder and chronic hepatitis was confirmed. We believe that this is
      the first reported case of a hypoplasia of the left hepatic lobe coexisting with
      floating gallbladder.

PMID- 9756015
TI  - Metastasis and invasion of hepatocellular carcinoma mimicking a right adrenal
      tumor.
AB  - A 60-year-old man presented with a large right adrenal mass. Adrenal primary
      carcinoma invading the liver and retrohepatic inferior vena cava was suspected
      after preoperative imagings, which included ultrasonography, computed tomography,
      selective hepatic and adrenal angiography, and magnetic resonance imaging. An en
      bloc resection of the right kidney, right adrenal gland, posterior hepatic
      segment, and laterodorsal of the vena cava was performed using an active veno
      venous bypass. The defect of the inferior vena cava was closed using a 6 x 10 cm
      patch of horse pericardium. The cut surface of the resected specimens revealed a
      smaller necrotic intrahepatic tumor as well as a large extrahepatic tumor which
      involved the right adrenal gland and extended continuously to the liver,
      mimicking an adrenal tumor. As the histological features of the two tumors
      disclosed the same moderately differentiated hepatocellular carcinoma with a
      trabecular or pseudoglandular pattern, a huge mass of the right adrenal gland
      with invasion into the right lobe of the liver, which mimicked a primary adrenal
      tumor, was diagnosed as metastatic hepatocellular carcinoma from a primary
      hepatic tumor.

PMID- 9756016
TI  - Comparison of different endocrine stimulation tests in nondiabetic patients with
      chronic pancreatitis.
AB  - BACKGROUND/AIMS: The purpose of this study was to evaluate endocrine functional
      impairment in nondiabetic patients with chronic pancreatitis and to determine its
      reliability in the staging of this disease. METHODOLOGY: Eighteen patients with
      chronic pancreatitis and fasting normoglycemia (fasting blood glucose level < 100
      mg/dl) and 10 healthy subjects underwent an oral glucose tolerance test (OGTT),
      an intravenous glucose test (IGT) and an arginine stimulation test (AST). Blood
      glucose and serum concentrations of insulin, C-peptide and glucagon were measured
      before and after stimulation. Exocrine pancreatic function was assessed by the
      pancreolauryl serum test (PLT), and morphological changes were staged by
      endoscopic retrograde pancreaticography (ERP), which were rated as I (mild), II
      (moderate) or III (severe). RESULTS: Glucagon and C-peptide secretions after
      arginine stimulation were reduced in patients with moderate and severe chronic
      pancreatitis while no parameter was able to show impaired endocrine function in
      the early stage (ERP I) of the disease. Serum insulin concentrations proved to be
      of no use in the diagnosis of pathological B-cell function, since even patients
      with severe chronic pancreatitis and fasting normoglycemia demonstrated normal
      insulin secretion. CONCLUSIONS: We conclude that there is a close correlation
      between morphological changes of the pancreas and functional endocrine reserve
      capacity, whereas endocrine stimulation tests were not shown to be helpful in the
      clinical assessment of nondiabetic patients with chronic pancreatitis.

PMID- 9756017
TI  - Duodenum-preserving resection of the pancreatic head for mucinous ductal ectasia
      without overt carcinoma.
AB  - BACKGROUND/AIMS: The clinical characteristics of mucinous ductal ectasia (MDE) of
      the pancreas without overt carcinoma have not been clarified. To clarify MDE and
      assess the optimal treatment procedure, including the technique of duodenum
      preserving resection of the pancreatic head (DpRPH), we studied four patients.
      METHODOLOGY: Our patients consisted of three men and one woman, with a mean age
      of 71 years. The patients underwent DpRPH (n=3) or the pylorus-preserving Whipple
      procedure (PpW) (n=1). Clinicopathological features, postoperative pancreatic
      function, and technique to preserve duodenal blood flow were studied. RESULTS:
      All patients had intraductal mucin-hypersecretion and multilocular cysts lined by
      hyperplastic epithelium. The lesions were located in the uncinate process (n=3)
      or head-body (n=1) of the pancreas. DpRPH totally removed the lesions in the
      uncinate process. Of the three patients receiving DpRPH, dusky duodenum and a
      postoperative duodenal ulcer developed in two whose gastroduodenal arteries (GDA)
      were divided, but did not develop in one with undivided GDA. Postoperative
      glucose tolerance test and peptide para-aminobenzoic acid test after DpRPH showed
      better values than those after PpW. All patients are alive and well 22 to 40
      months after surgery. CONCLUSIONS: DpRPH is a new standard for MDE. During DpRPH,
      preservation of the GDA and the superior portion of the pancreatic head is
      recommended to maintain an adequate duodenal blood flow.

PMID- 9756018
TI  - Regional versus systemic chemotherapy for advanced pancreatic cancer: a
      randomized study.
AB  - BACKGROUND/AIMS: In an attempt to improve treatment protocols for advanced
      pancreatic cancer, the value of regional chemotherapy compared with systemic
      chemotherapy was investigated in this randomized study. METHODOLOGY: Fourteen
      patients with advanced non-resectable pancreatic adenocarcinoma were randomized
      receiving either systemic chemotherapy with mitomycin, mitoxanthrone and
      cisplatin (5pts.) or celiac axis infusion regional chemotherapy with SpherexR
      microembolization. In the systemic group one patient was stage III, four patients
      were stage IV, in the intraarterial group two patients were specified stage III
      and seven were stage IV. RESULTS: In the systemic group one stable disease and
      four progressive diseases were noted, in the regional group two stable diseases
      and seven partial responses were noted. Median survival was 11 weeks in the
      systemically treated patients versus 33 weeks in the patients treated with
      intraarterial infusion (p=0.001). One patient became resectable (R0).
      CONCLUSIONS: Performance status improved during regional chemotherapy whilst it
      steadily decreased in the patients treated systemically. The study was terminated
      at that point.

PMID- 9756019
TI  - AgNORs in duct epithelial lesions in chronic pancreatitis and in pancreas cancer
      cells.
AB  - BACKGROUND/AIMS: Argyrophilic nucleolar organizer regions (AgNORs) reflect the
      proliferative activity of cells. Since the majority of pancreatic cancers are
      ductal carcinomas, the aim of the study was to determine the AgNORs expression of
      potential pre-neoplastic ductal epithelial lesions in advanced chronic
      pancreatitis compared with pancreatic cancer cells. METHODOLOGY: Histological
      preparations obtained from 24 patients with chronic pancreatitis and 16 patients
      with pancreatic cancer were used to estimate the number of AgNORs per nucleus.
      Four types of AgNORs were distinguished and histograms with cell percentage of
      each type were performed for all forms of epithelial anomalies. RESULTS: In
      simple hyperplasia, squamous and mucous metaplasia the number of AgNORs ranged
      from 1.92 to 2.23; type I was predominant. In papillary hyperplasia, dysplasia
      and in situ carcinoma the number ranged from 2.98 to 3.34, with a predominance of
      type II-IV. In invasive carcinoma the number was 4.29 and 74% of cells were of
      type II-IV. CONCLUSIONS: Both counts of AgNORs and the percentage of type II-IV
      cells showed a gradual increase from simple hyperplasia through papillary
      hyperplasia and dysplasia to invasive carcinoma which in this respect differs
      significantly from all forms of the epithelial anomalies examined.

PMID- 9756020
TI  - End to side mucomucosal Wirsung jejunostomy after pancreaticoduodenectomy:
      immediate results and long term follow-up.
AB  - BACKGROUND/AIMS: Pancreatico-duodenectomy (PD) is nowadays a widely performed
      operation which still carries a risk of some morbidity and mortality due to
      leakage of the Pancreatico-jejunostomy. The aim of the present paper is to
      describe critically the experience of a surgical team with a large number of
      consecutive non-selective PDs, where the same surgical procedure was adopted in
      all cases to manage the pancreatic stump. METHODOLOGY: Sixty six Whipple/Child
      PDs and 4 Traverso-Longmire (Duodenum Preserving PD) were performed between 1974
      and 1993, by the same surgical team in our surgical department. The management of
      the pancreatic stump was always the same: a hand-made end-to-side mucomucosal
      Wirsung-jejunostomy, completed by a second layer between pancreatic capsula and
      jejunal sero-muscular wall. RESULTS: The overall mortality was 7.1% (5 cases).
      Only one death could be ascribed to pancreatico-jejunostomy related complications
      (post-operative acute pancreatitis). Specific morbidity was 12.6% (9 cases). Only
      one complication was related to the Wirsung-jejunostomy (leakage of the
      anastomosis, treated by a "sleeve" end-to-end pancreato-jejunostomy). Long-term
      patency of the anastomosis was shown by ERCP. CONCLUSIONS: Even if this
      anastomotic technique requires a little more time and attention by the surgeon,
      we think that the low incidence of pancreatico-jejunal anastomosis related
      complications represents a validation of the method, and a motivation to adopt
      this anastomotic technique. The long-term patency of the muco-mucosal Wirsung
      jejunostomy is another valid argument that supports this kind of management of
      the pancreatic stump after PD.

PMID- 9756021
TI  - Pancreatic trauma in patients with pancreatobiliary anomaly.
AB  - One patient with a choledochal cyst and anomalous pancreaticobiliary junction had
      pancreatic transection causing bile peritonitis. Intraoperative
      cholangiopancreatography revealed this anomaly. In another patient with pancreas
      divisum, cannulation of the minor papilla (ERCP) demonstrated focal stenosis of
      the dorsal pancreatic duct, corresponding to the site of the minor laceration.
      The possibility of a coexisting pancreatobiliary anomaly should be considered in
      the diagnosis of pancreatic trauma, particularly in terms of the interpretation
      of pancreatograms.

PMID- 9756022
TI  - Advanced small cell pancreatic cancer: relevance of laparoscopic staging.
AB  - Small cell pancreatic cancer is a rare pancreatic malignancy. Thus, it offers
      substantial therapeutic perspectives. As demonstrated in this case, surgical
      laparoscopy might not only be used for staging in resectable pancreatic cancers
      but also in advanced cases for adequate tissue sampling and rapid diagnosis.

PMID- 9756023
TI  - Idiopathic hyperamylasemia.
AB  - A 25-year-old pregnant Japanese woman was diagnosed with idiopathic
      hyperamylasemia. The administration of a beta-stimulant caused a further increase
      in the serum levels of pancreas-type amylase and lipase.The patient's
      hyperamylasemia concomitant with elevated serum levels of lipase, elastase 1, and
      trypsin lasted over a 4 year-period, in which the patient remained asymptomatic.
      It is possible that the pancreas in some women with the idiopathic
      hyperamylasemia can respond to a beta-adrenoceptor stimulation with respect to
      pancreatic enzyme secretion.

PMID- 9756024
TI  - Management of the pancreatic metastases from renal cell carcinoma: report of four
      resected cases.
AB  - The pancreas is an uncommon site for metastasis from renal cell carcinoma. In
      most cases, pancreatic metastases occur as part of widespread nodal and visceral
      involvement, and there is thus evidence of metastatic disease elsewhere in the
      body. We present 4 cases with resectable pancreatic metastases arising from renal
      cell tumors without involvement of the regional lymph nodes at the operation.
      Three cases out of 4 were asymptomatic and the pancreatic metastases were
      detected by routine follow-up examination of renal cell carcinoma. Aggressive
      surgical treatment for the solitary metastatic lesion is advocated. Spread of
      renal cell carcinoma to the pancreas is, however, via the hematogenous route, and
      even solitary pancreatic metastasis may be one of the manifestations of the
      systemic metastasis of renal cell carcinoma. No pancreatic regional lymph nodes
      metastases were noted. Pancreatectomy should be undertaken to remove the tumor
      with adequate resection margins while preserving as much of the gland as
      possible. The prognosis of pancreatic metastases arising from a renal cell
      carcinoma is discussed with a review of the literature. Adjuvant chemo- and
      endocrine therapy should also be considered in these cases.

PMID- 9756025
TI  - Injection sclerotherapy for gastric varices using N-butyl-2-cyanoacrylate and
      ethanolamine oleate.
AB  - BACKGROUND/AIMS: Tissue adhesive agents, such as the cyanoacrylates, have been
      used as an alternative to conventional sclerotherapy to treat gastric varices,
      but the long-term efficacy of this approach has not been determined. We evaluated
      the efficacy and long-term outcome of injection sclerotherapy with n-butyl-2
      cyanoacrylate and ethanolamine oleate in 16 patients with gastric varices.
      METHODOLOGY: We evaluated the effect of injection sclerotherapy in 16 Japanese
      patients with gastric varices. Injection sclerotherapy was performed on an
      emergency basis in 6 patients, an elective basis in 5 patients, and as
      prophylaxis in 5 patients. RESULTS: No bleeding was observed in the 7 patients in
      whom gastric varices disappeared during the 51 month follow-up period. The non
      bleeding rate after treatment was significantly higher in this group than in the
      9 patients in whom gastric varices did not disappear (p<0.05). Acute bleeding was
      stopped in 5 (83.3%) of 6 patients. The single failure was a patient in whom the
      sclerosant could not be injected into the gastric varices. No serious
      complications, such as emboli in other organs, were observed. CONCLUSION: The
      results suggest that this therapy is a safe and useful treatment for gastric
      varices and that the goal of injection sclerotherapy should be the disappearance
      of gastric varices.

PMID- 9756027
TI  - Gastric emptying and antral myoelectrical activity in chronic alcoholics with
      dyspepsia.
AB  - BACKGROUND/AIMS: Chronic alcoholism is known to effect gastric motor activity. An
      association between gastric motility disorders and abnormal myoelectrical
      activity has been observed in various gastrointestinal and extra-intestinal
      diseases. The aim of this study was to investigate the effect of chronic
      alcoholism on gastric emptying and antral myoelectrical activity. METHODOLOGY:
      Electrogastrography (EGG) was performed on 20 chronic alcoholics with chronic
      dyspepsia using a pair of electrodes sonographically placed on the skin overlying
      the gastric antrum. After an overnight fast, patients were tested over a period
      of one hour in the a) fasting and b) fed state, after ingestion of a 370 kcal
      liquid-solid test meal. The following EGG parameters were determined: dominant
      frequency (DF (cpm); DF (%) in the normal range (2-4 cpm); bradygastria (<2 cpm);
      tachygastria (4-10 cpm); dominant frequency instability coefficient (DFIC), and
      postprandial to fasting power ratio (PR). The data were correlated with results
      obtained from 20 controls matched for age and sex. In 18 alcoholics, the EGG data
      were compared to the percentage of radionuclides (liquid phase labeled with 99m
      Tc colloid) remaining in the stomach after 60 minutes (%) (gamma camera system).
      Moreover, for the alcoholics, various parameters such as ethanol consumption, and
      gastrointestinal symptoms were determined and related to EGG values and
      scintigraphy. RESULTS: About 50% of the alcoholics showed delayed gastric
      emptying compared to normal values previously reported (t 60 values: >68%). In
      opposite to scintigraphy, the alcoholics did not exhibit abnormalities in antral
      myoelectrical activity. They had significantly decreased bradygastria measures
      compared to controls (p<0.05). The scintigraphic t 60 values did not correlate
      either with EGG values or with dyspepsia and clinical parameters. EGG values did
      not correlate with dyspepsia. However, increased preprandial DF was significantly
      correlated with ethanol consumption. CONCLUSIONS: Chronic alcoholism induces a
      disturbance of gastric emptying, probably resulting from toxic damage of the
      gastrointestinal smooth muscles. Disturbances in antral myoelectrical activity
      were not found.

PMID- 9756026
TI  - Significant risk factors of recurrence in muscularis proprial carcinoma of the
      stomach.
AB  - BACKGROUND/AIMS: The aim of this study is to elucidate significant risk factors
      of recurrence in muscularis proprial gastric cancer (MPGC). METHODOLOGY: Seventy
      three patients who underwent curative gastrectomy for MPGC were divided into 14
      patients with postoperative recurrence (Group 1) and 59 patients without
      recurrence (Group 2). A retrospective study of Group 1 compared the
      clinicopathological features with Group 2. RESULTS: There were no significant
      differences of age, gender and operative method including frequency of lymph node
      dissection between Group 1 and Group 2. Although tumor size, gastric location and
      histological type did not significantly differ between the two groups, the rate
      of Borrman type in Group 1 (71.4%) was significantly higher than in Group 2
      (42.4%). Significant risk factors of recurrence in pathological findings were the
      presence of secondary lymph node metastasis or more, lymphatic and venous
      involvement. Median survival in Group 1 (28.8 months) was significantly worse
      than in Group 2 (59.0 months). The 1-year, 3-year, and 5-year survival rates
      between Group 1 versus Group 2 were 71.4% versus 98.3% (p<0.01), 28.6% versus
      96.7% (p<0.01), and 7. 1% versus 95.0 (p<0.01), respectively. CONCLUSIONS:
      Prognosis of the postoperative recurrence in MPGC was very poor. More careful
      prophylactic treatment against recurrence of MPGC should therefore, be prescribed
      in patients with the aforementioned risk factors of recurrence.

PMID- 9756028
TI  - Gastric re-resection in emergency.
AB  - BACKGROUND/AIMS: We reviewed a consecutive series of patients with acute
      complications following gastric resection, in order to evaluate the role of
      gastric re-resection as the operation of choice in emergency. METHODOLOGY:
      Records of 90 patients with acute complications following gastric resection
      observed from January 1991 to January 1996 were retrospectively analyzed.
      RESULTS: Hemorrhagic events occurred in the vast majority of cases (87), either
      as acute complications after a long time since surgery (78 cases) or as early
      postoperative complications (9). Among late acute complications, three cases were
      related to bleeding cancer of the gastric stump. Anastomotic obstructions
      presenting as acute complications occurred in 3 cases. Emergency surgery was
      indicated in three cases of acute obstruction, in 1 case of bleeding cancer of
      the gastric stump, in 9 (12%) out of the 75 remaining late acute hemorrhagic
      complications and in 1 (11%) out of 9 early hemorrhagic complications. Completion
      gastrectomy was chosen in the one case of bleeding cancer of the gastric stump
      with indication for emergency surgery. Gastric re-resection was performed in 11
      cases: 9 for hemorrhagic complications and 2 for obstructive acute complications.
      In two cases, one for hemorrhage and one for occlusion, other surgical procedures
      were carried out. CONCLUSIONS: Gastric re-resection can represent the most
      suitable operation in acute complications following gastric resection.

PMID- 9756029
TI  - The relationship between stapling doughnuts: characteristics and functional
      results after total gastrectomy.
AB  - BACKGROUND/AIMS: The objective of this study was to determine whether the
      thickness of the esophageal doughnut is related to postoperative results in total
      gastrectomy. METHODOLOGY: Thirty-eight total gastrectomy patients were studied,
      including 18 who underwent jejunal pouch reconstruction and 20 who did not have
      pouch reconstruction. We used the Proximate-ILS circular stapler, with purse
      string suturing at the cut end of the esophagus performing only the mucosal layer
      manually in all cases. We divided the esophageal doughnuts after stapling into
      two groups: Group A: doughnut involving muscle tissue of 0-25% of the esophageal
      circumference; Group B: doughnut involved muscle tissue of 25-100% of the
      esophageal circumference. Reflux scores and the scintigraphic reflux index were
      determined. RESULTS: No significant difference was found between the two groups
      in reflux score or scintigraphic reflux index. CONCLUSIONS: These findings
      indicate that the degree of postoperative reflux esophagitis was not affected by
      the amount of the muscular layer included in the esophageal doughnut. Continuity,
      and not variability of the degree of involved muscle in the esophageal doughnut,
      is an important factor at the time of stapling.

PMID- 9756030
TI  - Gastric cancer with metastases to the distant peritoneum: a 20-year surgical
      experience.
AB  - BACKGROUND/AIMS: The efficacy of palliative gastrectomy in gastric cancer with
      peritoneal metastases remains uncertain. The aim of the present study was to
      evaluate the benefits of gastrectomy on the postoperative course of patients with
      gastric cancer and simultaneous metastases to the distant peritoneum.
      METHODOLOGY: A total of 122 patients who had gastric cancer and metastases to the
      distant peritoneum were studied with respect to survival. RESULTS: The extent of
      peritoneal metastases did not significantly affect the prognosis. Moreover,
      multivariate analysis indicated that surgery without gastrectomy was the only
      significant prognostic factor (relative risk, 2.587). CONCLUSIONS: Our results
      suggest that the decision to perform gastrectomy does not depend on the extent of
      peritoneal metastasis in gastric cancer. Furthermore, palliative gastrectomy, if
      feasible, seems to have a beneficial effect on the postoperative course and is
      indicated for patients regardless of metastasis to the peritoneum, if the primary
      tumor is surgically resectable and there is no evidence of liver metastasis.

PMID- 9756031
TI  - Modulation of volitional ethanol intake in the rat by central delta-opioid
      receptors.
AB  - The acute effect of opioid antagonists on volitional ethanol intake was studied
      in unselected Sprague-Dawley rats using a two-bottle, free-choice model. The
      total daily intake of ethanol during saline treatment was 1.79 +/- 0.4 g/kg/day
      (n = 136). The rats were deprived of fluids for the last 4 hr of the light
      period. Saline or drug was given intraperitoneally 20 to 30 min before the onset
      of dark, and the ethanol and water intakes were measured during the following
      hour. The ethanol intake during this hour was 0.75 +/- 0.06 g/kg (n = 136).
      Naltrexone significantly reduced ethanol intake. There was also a significant
      reduction in ethanol intake following administration of ICI-174,864. Naloxonazine
      and naloxone methiodide lacked effect. None of the treatments had any effect on
      the water or food intake. The results suggest that central delta-opioid receptors
      modulate volitional ethanol intake in the rat.

PMID- 9756032
TI  - Effects of nicotine and mecamylamine microinjections into the nucleus accumbens
      on ethanol and sucrose self-administration.
AB  - Nicotine (NIC) and ethanol (ETOH) are both drugs of abuse that can affect similar
      pathways in the central nervous system. However, the role of nicotinic processes
      in ETOH's reinforcing actions is unclear. Although the mesolimbic dopamine
      systems are known to be involved in the reinforcing effects of ETOH, the role of
      nicotinic receptors within the nucleus accumbens (NAc) in ETOH reinforcement has
      not been studied. To address this issue, adult male Long-Evans rats were
      initiated to self-administer ETOH (10% v/v, n = 14) using the sucrose
      substitution procedure or sucrose (5% w/v, n = 8) in a 30-min operant session.
      They were then surgically implanted with bilateral stainless-steel guide cannulae
      to allow for microinjection into the core of the NAc. After recovery from
      surgery, presession microinjections of NIC (0.3, 3.3, 10, 30, and 60 microg/1
      microl/brain) or the antagonist mecamylamine (MEC) (1, 3, 10, 30, and 60 microg/1
      microl/brain) were performed prior to an ETOH or sucrose self-administration
      session. NIC (3.3 and 60 microg/microl) and MEC (30 microg/microl) both reduced
      ETOH self-administration behavior, without affecting sucrose-reinforced behavior.
      A reduction in the total duration of ETOH responding (termination) was also
      observed after either 60 microg/microl of NIC and 30 microg/microl of MEC. The
      lack of a clear dose-response relationship for the agonist and the antagonist
      indicates that the interaction between the NAc nicotinic system and ETOH self
      administration is complex.

PMID- 9756034
TI  - Chronic ethanol treatment leads to increased ornithine decarboxylase activity:
      implications for a role of polyamines in ethanol dependence and withdrawal.
AB  - Recent research has focused on the N-methyl-D-aspartate receptor system as a
      major site of ethanol action in the brain and specifically on compensatory
      changes in the expression of the polyamine-sensitive NR2B subunit. Therefore, we
      examined the effects of chronic ethanol treatment on polyamine homeostasis in the
      rat brain. Wistar rats were made dependent by ethanol vapor inhalation. This
      caused a rise in hippocampal ornithine decarboxylase (ODC) activity that was
      correlated with the appearance of physiological dependence. ODC activity returned
      to control levels within 3 days of ethanol withdrawal. Enzyme activity also
      increased in the cerebral cortex, striatum, and cerebellum of the ethanol
      dependent rats. The concentration of the polyamines (putrescine, spermidine, and
      spermine) in the hippocampus was increased in ethanol-dependent rats. Injection
      of the ODC inhibitor, alpha-difluoromethylornithine (500 mg/kg) at the onset of
      withdrawal resulted in a significant reduction in the severity of withdrawal
      behaviors. The level of ODC activity and the severity of withdrawal behaviors
      were positively correlated. Perturbed polyamine homeostasis may represent an
      important molecular component in the initiation of ethanol withdrawal behaviors
      in the ethanol-dependent rat.

PMID- 9756033
TI  - Reversal of ethanol-induced testosterone suppression in peripubertal male rats by
      opiate blockade.
AB  - Teenage drinking is a major problem in the United States, as well as abroad.
      Besides psychosocial implications, ethanol (EtOH) has detrimental effects on the
      reproductive system. Clinical problems associated with reduced reproductive
      hormones include osteoporosis, decreased muscle function, anemia, altered immune
      function, prostate involution, and decreased reproductive abilities. Education
      coupled with strategies aimed at preventing these deleterious consequences even
      in the face of continued EtOH intake is extremely important. We have tested the
      possibility that naltrexone, a drug currently used in patients to decrease
      alcohol craving, might also prevent the fall in the male hormone, testosterone,
      caused by EtOH exposure. Rats aged 35 days old (prepubertal), 45 days old
      (midpubertal), and 55 days old (late pubertal) were injected (intraperitoneally)
      with either saline, EtOH, naltrexone, or EtOH plus naltrexone. In the two older
      age groups, EtOH significantly suppressed testosterone, which was prevented by
      administration of naltrexone. In the youngest animals, there was no treatment
      effect presumably due to low basal levels of testosterone. EtOH similarly reduced
      luteinizing hormone (LH), but this suppression was not prevented by naltrexone.
      There was no consistent effect of any treatment on hypothalamic concentration of
      pro-LH releasing hormone (RH) (LHRH), LHRH, or on steady-state levels of LHRH
      mRNA. We conclude that, as animals progress through puberty, EtOH suppresses LH
      and testosterone. The testosterone decline can be prevented by opiate blockade
      with naltrexone, an effect primarily seen at gonadal level. Thus, naltrexone, a
      drug already used clinically to reduce EtOH intake, also has protective
      physiological effects on the endocrine system.

PMID- 9756036
TI  - Long-term ethanol consumption selectively impairs ganglioside pathway in rat
      brain.
AB  - Gangliosides are sialo-glycosphingolipids that play important roles in the
      interaction of cells with their environment and are thus involved in the
      regulation of many cellular events. Sialic acid residues are important for the
      conformation of a glycomolecule, their structural stability and their functions.
      Although decreased brain ganglioside sialic acid has been previously reported as
      a result of chronic ethanol treatment in rats, no reports are available on the
      sialylation of specific gangliosides and/or the mechanism leading to depletion of
      their sialic acid residues. Therefore, in this investigation, we have examined
      the effects of chronic ethanol treatment on (1) incorporation of [4,5-3H]N
      acetylmannosamine (ManNAc) into specific rat brain gangliosides, GD3, GD1a, GT1a,
      and GT1b; and (2) enzymatic activities of brain sialyltransferase and sialidase
      at specific subcellular levels. The experiments were done in male Wistar rats
      pair-fed with either ethanol or control liquid diets for a period of 8 weeks. The
      rats were intracerebroventricularly injected with labeled ManNAc (30 microCi/rat)
      and killed after 90 min. Radioactivity was determined in respective ganglioside
      bands separated on a thin layer chromatography system. Specific activities of
      sialyltransferase and sialidase were assessed using GM3 and GD3 as substrates,
      respectively. The results showed significant decreases of 57.7% (p < 0.001) and
      68.9% (p < 0.001), respectively, in the labeled ManNAc incorporation into GD3 and
      GD1a fractions in rats of the ethanol group, compared with rats of the control
      group. No significant changes were noted in the incorporation of labeled ManNAc
      into GT1a or GT1b ganglioside fractions between the ethanol and control groups.
      Concomitantly, compared with control rats, a decrease of 18.9% (p < 0.05), 20.6%
      (p < 0.05), and 15.8% (p < 0.001) was found in the sialyltransferase activity,
      respectively, at the whole brain, and brain Golgi and synaptosomal levels.
      However, dramatic increases of 32.4% (p < 0.05), 105% (p < 0.001), and 150% (p <
      0.001) in sialidase activity were found, respectively, at the whole brain and
      brain cytosol and synaptosomal fractions of rat treated chronically with ethanol.
      Thus, we conclude that the deleterious actions of ethanol on the sialylation of
      rat brain gangliosides is specific, and the reduced sialic acid label found in
      GD3 and GD1a in this study is mainly due to increased activity of brain
      sialidase. Furthermore, the study reaffirms our tenet that, regardless of whether
      it is the liver or the brain, glycosylation cascade is one of the main target of
      the deleterious attacks of ethanol.

PMID- 9756035
TI  - Identification of the human P-450 enzymes responsible for the sulfoxidation and
      thiono-oxidation of diethyldithiocarbamate methyl ester: role of P-450 enzymes in
      disulfiram bioactivation.
AB  - Diethyldithiocarbamate methyl ester (DDTC-Me) is a precursorto the formation of S
      methyl-N,N-diethylthiolcarbamate sulfoxide, the active metabolite proposed to be
      responsible for the alcohol deterrent effects of disulfiram. The present study
      investigated the role of human cytochrome P-450 (CYP) enzymes in sulfoxidation
      and thiono-oxidation of DDTC-Me, intermediary steps in the activation of
      disulfiram. Several approaches were used in an attempt to delineate the
      particular P-450 enzyme(s) involved in the sulfoxidation and thiono-oxidation of
      DDTC-Me. These approaches included the use of cDNA-expressed human P-450 enzymes,
      correlation analysis with sample-to-sample variation in human P-450 enzymes in a
      bank of human liver microsomes, and chemical and antibody inhibition studies.
      Multiple human P-450 enzymes (CYP3A4, CYP1A2, CYP2A6, and CYP2D6) catalyzed the
      sulfoxidation of DDTC-Me, as determined with cDNA-expressed enzymes. Several
      lines of evidence suggest that the sulfoxidation of DDTC-Me by human liver
      microsomes is primarily catalyzed by CYP3A4/5, including (1) a high correlation
      between DDTC-Me sulfoxidation and testosterone 6beta-hydroxylation; (2) increased
      DDTC-Me sulfoxidation in the presence of alpha-naphthoflavone, an activator of
      CYP3A enzymes; (3) inhibition of this reaction by inhibitors of CYP3A4/5 enzymes,
      such as troleandomycin and ketoconazole; and (4) inhibition of DDTC-Me
      sulfoxidation by antibodies against CYP3A enzymes. On the other hand, several
      lines of evidence suggested that the thiono-oxidation of DDTC-Me by human liver
      microsomes is catalyzed in part by CYP1A2, CYP2B6, CYP2E1, and CYP3A4/5,
      including (1) these human P450 enzymes among others have the capacity to catalyze
      this reaction, as determined with cDNA-expressed enzymes; (2) a high correlation
      between DDTC-Me thiono-oxidation and testosterone 6beta-hydroxylation, weak
      inhibition by ketoconazole, troleandomycin, and anti-CYP3A antibodies suggested a
      minor role for CYP3A4; (3) a high correlation with immunoreactive CYP2B6
      suggested involvement of this enzyme; (4) weak inhibition of DDTC-Me thiono
      oxidation by furafylline and anti-CYP1A antibody suggested involvement of CYP1A2;
      and (5) inhibition of DDTC-Me thiono-oxidation by DDTC and anti-CYP2E antibodies
      suggested a role for CYP2E1. Collectively, these data suggested CYP3A4/5 enzymes
      are the major contributors to the sulfoxidation of DDTC-Me by human liver
      microsomes, and CYP1A2, CYP2B6, CYP2E1, and CYP3A4/5 contribute toward DDTC-Me
      thiono-oxidation by human liver microsomes. This study, in conjunction with
      others (Madan et al., Drug Metab. Dispos. 23:1153-1162, 1995), may help explain
      the variability in disulfiram's effectiveness as an alcohol deterrent.

PMID- 9756037
TI  - A characterization of approach and avoidance learning in alcohol-preferring and
      alcohol-nonpreferring rats.
AB  - Although numerous biochemical and physiological differences have been shown to be
      correlated with alcohol preference, less is known about behavioral factors that
      may correlate with alcohol preference. Using a signaled barpressing task, alcohol
      preferring (P; n = 18) and alcohol-nonpreferring (NP; n = 19) rats were compared
      for their ability to learn an appetitive and an aversive task. Results showed
      that P rats had difficulty learning the tasks in comparison with NP and
      nonselected, control rats when appetitive training was given first. However, if
      aversive training came first, the NP rats performed poorly in comparison with the
      P and nonselected rats. These results suggest that these lines of rats may differ
      in behavioral inhibition and sensitivity to conditioned fear. Furthermore, these
      behavioral differences may offer a richer analysis of the traits that were co
      selected with the alcohol-seeking and alcohol-avoiding phenotypes.

PMID- 9756038
TI  - Ethanol-induced conditioned taste aversion in BXD recombinant inbred mice.
AB  - Genetic differences in sensitivity to ethanol's aversive effects may play an
      important role in the development of alcohol-seeking behavior and alcoholism. The
      present study examined the development of ethanol-induced conditioned taste
      aversion in 20 BXD/Ty recombinant inbred strains of mice and their progenitor
      inbred strains, C57BL/6J (B6) and DBA/2J (D2). Adult male mice were given 1-hr
      access to a saccharin-flavored solution every 48 hr for 12 days. After all but
      the first and last saccharin access periods, they received ethanol injections (0,
      2, or 4 g/kg, i.p.). Separate groups of unpaired control mice received 4 g/kg of
      ethanol 1 hr after water access. Saline control mice were also used for examining
      preference across a wide range of saccharin concentrations (0.019 to 4.864% w/v).
      As expected, saccharin consumption during taste conditioning declined over
      conditioning trials in a dose-dependent manner, indicating development of ethanol
      induced conditioned taste aversion. Correlational analyses using strain means
      from recently published papers indicated no significant genetic correlation
      between taste conditioning and two phenotypes thought to reflect ethanol
      reinforcement or reward (ethanol drinking, conditioned place preference).
      However, there were significant genetic correlations between taste conditioning
      at the high dose and sensitivity to ethanol-induced hypothermia, rotarod ataxia,
      and acute withdrawal. Quantitative trait locus (QTL) analyses of strain means
      indicated that taste aversion was associated (p < 0.01) with genetic markers on
      nine chromosomes (1, 2, 3, 4, 6, 7, 9, 11, and 17). These QTLs were located near
      several candidate genes, including genes encoding several different acetylcholine
      receptor subunits, the delta opioid receptor, and two serotonin receptors (1B and
      1D). QTLs for saccharin preference were located on several of the same
      chromosomes (2, 3, 4, 6, and 11). Two of these saccharin QTLs overlap candidate
      genes influencing sensitivity to sweet or bitter taste stimuli. In general, these
      findings support the conclusion that multiple genes influence ethanol-induced
      conditioned taste aversion. Some of these genes appear to influence taste
      sensitivity, whereas others appear to mediate sensitivity to aversive
      pharmacological effects of ethanol.

PMID- 9756039
TI  - The effects of chronic ethanol consumption on the formation of
      phosphatidylethanolamine molecular species and their appearance at the plasma
      membrane.
AB  - The purpose of our study was to determine whether chronic ethanol consumption
      affected membrane assembly by altering the formation of specific molecular
      species of phosphatidylethanolamine (PE) and their subsequent incorporation into
      the plasma membrane (PM). We investigated the effects on the PE species made by
      the two major pathways in hepatocytes: (1) from CDP-ethanolamine in the
      endoplasmic reticulum, and (2) by the decarboxylation of phosphatidylserine (PS)
      in the mitochondria. Ethanol consumption exerted significant effects on the
      formation of ethanolamine-derived PE species and affected mainly two species, the
      16:0/22:6 and 18:0/20:4 species. In cultured hepatocytes from ethanol-fed rats
      labeled with [3H]ethanolamine for 0.25 to 4 hr, the amount of the [3H]16:0/22:6
      PE species was decreased compared with that in control cells, whereas the amount
      of [3H]18:0/20:4 species was increased. The amount of the [3H]16:0/22:6 PE
      species on the cell surface was also decreased in hepatocytes from ethanol-fed
      rats, whereas the amount of [3H]18:0/20:4 species was increased. In contrast, the
      profile of [3H]PE species formed in cells treated with [3H]serine exhibited minor
      alterations, and the profile of the serine-derived [3H]PE species on the cells
      surface was not altered after 4 hr of labeling. The changes in ethanolamine
      derived species were apparently caused by time-dependent alterations in the
      metabolic processes, because the presence of 110 mM ethanol in the culture media
      did not affect the profiles of [3H]PE species in cells from control or ethanol
      fed rats and was not required to sustain the altered profiles. The results
      indicate that the synthesis of specific PE molecular species and their appearance
      on the PM may occur by compartmentalized processes which are distinguishable by
      different sensitivities to ethanol consumption. The results indicate that ethanol
      consumption may contribute alcoholic hepatic injury by interfering with the
      metabolism of specific PE molecular species and their assembly into the PM.

PMID- 9756040
TI  - Effect of prenatal ethanol exposure on the developmental profile of the NMDA
      receptor subunits in rat forebrain and hippocampus.
AB  - The effects of prenatal ethanol exposure on the NMDAR1 protein expression
      (postnatal days 1 and 7) and on the developmental profile of the NMDAR2A and
      NMDAR2B subunits in rat forebrain and hippocampus were investigated. Forebrain
      and hippocampal membrane proteins were isolated from pups of various ages
      (postnatal days 1 to 21) from prenatally ethanol exposed, pair-fed and ad libitum
      control groups. A semiquantitative immunoblot procedure was used with antibodies
      raised against the NMDAR1, NMDAR2A, and the NMDAR2B subunits to assess the NMDA
      subunit protein expression in the samples. NMDAR1 protein expression was
      unaffected by prenatal ethanol exposure at postnatal day 1 or 7 in both the
      forebrain and hippocampus. NMDAR2A protein expression levels rose rapidly in both
      forebrain and hippocampus during the time frame of study. Prenatal ethanol
      exposure caused a significant reduction in protein expression levels of the
      NMDAR2A in forebrain through postnatal day 14. NMDAR2B protein expression levels
      were high throughout the study in both forebrain and hippocampus. Prenatal
      ethanol exposure significantly reduced protein expression of the NMDAR2B in the
      forebrain (through postnatal day 14) and hippocampus (up to day 7). The results
      suggest that there may be a link between the depressed expression of the NMDAR2
      subunits and the neurodevelopmental disorders associated with fetal ethanol
      exposure.

PMID- 9756042
TI  - Development of rapid tolerance to ethanol-stimulated serotonin release in the
      ventral hippocampus.
AB  - This study was designed to examine the effects of acute intraperitoneal (i.p.)
      ethanol injection on the extracellular levels of serotonin (5-HT) in the ventral
      hippocampus (vHIP) and to determine whether a single prior exposure to ethanol
      could alter the response to a second dose of ethanol given 24 hr later. In the
      first experiment, in vivo microdialysis coupled with high pressure liquid
      chromatography-electrochemical detection (HPLC-EC) was used to assess the effects
      of 1.0, 1.75, and 2.5 g/kg ethanol on vHIP 5-HT extracellular levels in ethanol
      naive adult male Wistar rats. The largest dose significantly increased the
      extracellular concentration of 5-HT (p < 0.001) to a maximum of approximately
      180% of baseline values within 50 min; thereafter, the levels of 5-HT began to
      return toward baseline. The 1.75 g/kg dose also transiently increased 5-HT levels
      above baseline; however, no significant increase was observed with 1.0 g/kg
      ethanol. The results of the second experiment demonstrated that the i.p. dose of
      2.5 g/kg ethanol had no significant effect on the extracellular levels of 5-HT if
      rats had been given a single i.p. 2.5 g/kg dose of ethanol 24 hr earlier. Because
      the vHIP receives a major 5HT input from the median raphe nucleus (MRN), the
      results suggest that acute ethanol activates the MRN 5-HT system projecting to
      the vHIP and that rapid tolerance develops to the activating effects of alcohol
      on this pathway.

PMID- 9756041
TI  - Effect of ethanol drinking on the gene expression of opioid receptors,
      enkephalinase, and angiotensin-converting enzyme in two inbred mice strains.
AB  - There is convincing evidence that genetic factors contribute to the
      predisposition to alcoholism. In this respect, alcohol-preferring (like C57BL/6
      mice) and alcohol-avoiding lines (like DBA/2 mice) of animals served as models in
      the search for neurobiological substrates of excessive ethanol consumption. One
      of the systems that is thought to be associated with the incidence of alcoholism
      is the endogenous opioid system. In the first experiment, basal mRNA levels of mu
      and delta-opioid receptors, and of opioid-degrading enzymes enkephalinase
      (neutral endopeptidase 24.11; NEP) and angiotensin-converting enzyme (ACE) in the
      brain regions of C57BL/6 and DBA/2 mice did not reveal genetically determined
      differences in these parameters between the two strains. Furthermore, in the
      brain regions studied, the corresponding enzyme activities of NEP and ACE did not
      differ significantly between the lines of mice, except for a higher NEP activity
      in the striatum and olfactory bulb of DBA/2 mice (p < 0.01). In the second
      experiment, C57BL/6 and DBA/2 mice were offered a free choice between water and
      10% ethanol solution for 4 weeks and were killed thereafter; from another group,
      ethanol was removed for 3 days and from a third group ethanol was removed for 3
      weeks before killing. In the striatum, a highly significant increase in the ACE
      mRNA amount was detected after 3 weeks of removal of ethanol in C57BL/6 mice,
      whereas in DBA/2 mice the delta-opioid receptor mRNA level was increased at this
      time when compared with the corresponding ethanol treatment group. The most
      striking changes were seen in the hypothalamus, where mu-opioid receptor, ACE,
      and NEP mRNA amounts markedly decreased after ethanol treatment in both strains.
      Thus, chronic ethanol intake caused significant changes in the gene expression of
      distinct components of the endogenous opioid system. These findings further
      underline an involvement of the opioid system in the effects of ethanol.

PMID- 9756043
TI  - Early events in the development of neuronal polarity in vitro are altered by
      ethanol.
AB  - Among the neuropathological effects of prenatal exposure to ethanol is the
      disruption of neuromorphogenesis. The effects of ethanol on early events in the
      development of axons and dendrites were studied using cultured embryonic rat
      hippocampal neurons, which develop in vitro in a stereotypical sequence of events
      that mimics their development in vivo. During the first 24 hr in culture,
      hippocampal neurons attach to the substrate and develop into one of three stages
      identified by phase-contrast microscopy: (i) neurons having lamellipodia and no
      processes (stage 1); (ii) neurons developing minor processes (<40 microm) that
      subsequently become the cell's axon or dendrites (stage 2); or (iii) polarized
      neurons with at least one axon (process with length > or =40 microm) (stage 3).
      Exposure to ethanol (300 mg/dl or 800 mg/dl) in the culture medium resulted in an
      increase in both the number of minor processes per neuron and the number of stage
      3 neurons having more than the typical single axon. In addition, ethanol exposure
      significantly altered the proportion of neurons in the three early stages of
      development at 18 to 24 hr in vitro, without affecting overall neuron survival.
      With ethanol, there was a smaller proportion of neurons in the first stage of
      development, and a greater proportion of polarized stage 3 neurons. These
      findings suggest that ethanol alters the normal establishment of neuronal
      polarity, disrupting mechanisms that ensure the formation of the appropriate
      number of processes and that regulate the timing of process outgrowth.

PMID- 9756044
TI  - Ethanol counteraction of clonidine-evoked inhibition of norepinephrine release in
      rostral ventrolateral medulla of rats.
AB  - Previous studies from our laboratory demonstrated an antagonistic hemodynamic
      interaction between ethanol and clonidine in conscious and in urethane
      anesthetized rats. The present study tested the hypothesis that ethanol produces
      its effect by counteracting clonidine-evoked inhibition of norepinephrine (NE)
      release at its major site of action, the rostral ventrolateral medulla (RVLM). In
      vivo electrochemical measurement of real-time changes in NE level in the RVLM of
      urethane-anesthetized Sprague-Dawley rats was made along with blood pressure and
      heart rate. Clonidine (30 microg/kg, i.v.) produced significant decreases (p <
      0.05) in NE electrochemical signal and blood pressure. Ethanol (1 g/kg, i.v.)
      administered 10 min after clonidine significantly (p < 0.05) increased NE signal
      and counteracted clonidine-evoked hypotension. Equal volume of saline had no
      effect on NE signal in the RVLM nor on the hypotensive response to clonidine.
      Pretreatment with the same dose of ethanol (1 g/kg) caused slight increases in
      RVLM NE level and in blood pressure, but did not influence the electrochemical
      and blood pressure responses to clonidine; clonidine (30 microg/kg)
      administration 10 min after ethanol resulted in significant (p < 0.05) decreases
      in NE signal and blood pressure. These findings suggest that: (i) ethanol
      counteraction of the hypotensive action of clonidine involves, at least in part,
      opposite effects on central pathways that use NE as a neurotransmitter; (ii) the
      RVLM represents a possible site for the adverse hemodynamic interaction between
      ethanol and clonidine; and (iii) ethanol-evoked increase in RVLM NE, which
      correlates with its pressor effect, is much enhanced when RVLM NE level is
      reduced by clonidine.

PMID- 9756045
TI  - Acute effects of ethanol on recombinant kainate receptors: lack of role of
      protein phosphorylation.
AB  - This study examined the acute actions of ethanol on recombinant rat GluR6 kainate
      receptors expressed in Xenopus oocytes and HEK 293 cells. Electrophysiological
      recordings showed that co-application of ethanol with submaximal kainate
      concentrations resulted in similar inhibition of kainate-gated currents in both
      expression systems. Manipulation of intracellular phosphorylation pathways by
      intracellular dialysis with a solution without ATP and GTP did not modify the
      inhibitory effects of ethanol. Moreover, co-transfection of GluR6 receptor
      subunits with PKA-alpha catalytic subunit or the calcium/calmodulin-dependent
      protein kinase II (CamKII) catalytic fragment did not change the sensitivity of
      the receptor to ethanol. Treatment of Xenopus oocytes with specific inhibitors of
      PKC, PKA, CamKII, tyrosine kinases, and serine-threonine protein phosphatases did
      not affect the 100 mM ethanol-induced inhibition of GluR6 receptor-mediated
      currents. Biochemical experiments with transiently transfected HEK 293 cells
      confirmed published reports that GluR6 receptors are minimally phosphorylated
      under basal conditions in these cells and also revealed that acute ethanol did
      not increase GluR6 phosphorylation. These results suggest that, under our
      experimental conditions, ethanol inhibits recombinant GluR6 receptor function by
      a direct effect on the receptor rather than an indirect action via protein
      phosphorylation.

PMID- 9756046
TI  - Matching alcoholism treatments to client heterogeneity: Project MATCH three-year
      drinking outcomes.
AB  - This study reports 3-year outcomes for clients who had been treated in the five
      outpatient sites of Project MATCH, a multisite clinical trial designed to test a
      priori client treatment matching hypotheses. The main purpose of this study was
      to characterize the status of the matching hypotheses at the 3-year follow-up.
      This entailed investigating which matching findings were sustained or even
      strengthened across the 3-year study period, and whether any hypotheses that were
      not supported earlier eventually emerged at 3 years, or conversely, whether
      matching findings discerned earlier dissipated at this later time. This research
      also examines the prognostic effects of the client matching attributes,
      characterizes the overall outcomes at 37 to 39 months, and explores differential
      effects of the three treatments at extended follow-up. With regard to the
      matching effects, client anger demonstrated the most consistent interaction in
      the trial, with significant matching effects evident at both the 1-year and 3
      year follow-ups. As predicted, clients high in anger fared better in Motivational
      Enhancement Therapy (MET) than in the other two MATCH treatments: Cognitive
      Behavioral Therapy (CBT) and Twelve-Step Facilitation (TSF). Among subjects in
      the highest third of the anger variable, clients treated in MET had on average
      76.4% abstinent days, whereas their counterparts in the other two treatments (CBT
      and TSF) had on average 66% abstinent days. Conversely, clients low in anger
      performed better after treatment in CBT and TSF than in MET. Significant matching
      effects for the support for drinking variable emerged in the 3-year outcome
      analysis, such that clients whose social networks were more supportive of
      drinking derived greater benefit from TSF treatment than from MET. Among subjects
      in the highest third of the support for drinking variable, TSF participants were
      abstinent 16.1% more days than MET participants. At the lower end of this
      variable, difference in percent days abstinent between MET and TSF was 3%, with
      MET clients having more abstinent days. A significant matching effect for
      psychiatric severity that appeared in the first year posttreatment was not
      observed after 3 years. Of the 21 client attributes used in testing the matching
      hypotheses, 11 had prognostic value at 3 years. Among these, readiness-to-change
      and self-efficacy emerged as the strongest predictors of long-term drinking
      outcome. With regard to the overall outcomes, the reductions in drinking that
      were observed in the first year after treatment were sustained over the 3-year
      follow-up period: almost 30% of the subjects were totally abstinent in months 37
      to 39, whereas those who did report drinking nevertheless remained abstinent an
      average of two-thirds of the time. As in the 1-year follow-up, there were few
      differences among the three treatments, although TSF continued to show a possible
      slight advantage.

PMID- 9756047
TI  - Bone age and growth in fetal alcohol syndrome.
AB  - We have found delayed mean bone age in 63 children with fetal alcohol syndrome
      (FAS). The mean bone age Z-score for boys (n = 31) was -2.12 SDs and for girls (n
      = 32) was -1.62 SDs. This might suggest that they have potential for catch-up
      growth. However, experience with children with intrauterine growth retardation
      suggests that this will not be the case and that FAS children will be of reduced
      height at maturity. Further support for this assumption was gained from a sample
      of 26 patients who were followed until at least the age of 14 years for females
      and 16 years for males. There was no significant change in height Z-scores from
      early childhood to early adulthood, the mean score being -2.16 SDs and -2.11 SDs
      at mean ages of 4.83 years and 18.69 years, respectively. On the other hand,
      there were significant changes in weight and head circumference. The mean weight
      Z-score changed from -2.10 SDs to -1.14 SDs (p < 0.001). The head circumference
      mean Z-score in 16 patients was -3.13 SDs at a mean age of 2.79 years and -2.63
      SDs at a mean age of 17.37 years (p = 0.013). Short stature can continue to be
      used as a diagnostic criterion for FAS beyond childhood.

PMID- 9756049
TI  - Hyperhyaluronanemia in alcoholic hepatitis is associated with increased levels of
      circulating soluble intercellular adhesion molecule-1.
AB  - The purpose of this study was to evaluate the role of the sinusoidal endothelial
      cell (SEC) during the clinical course of alcoholic hepatitis. Twenty consenting
      patients (mean age: 49.4 +/- 11.0 years) with moderate or severe hepatitis were
      studied. The patients were selected and characterized according to their history
      of drinking and laboratory profile, including serum aminotransferases, bilirubin,
      total white blood cell and neutrophil count, and prothrombin times. C-reactive
      protein and interleukin-6 were also measured as markers of the hepatic acute
      phase response. A marker of the SEC functional state, the circulating level of
      hyaluronan, was measured in parallel with the circulating levels of soluble
      intercellular adhesion molecule (sICAM)-1 over a 6-month observation period. All
      patients were hospitalized for the first month and encouraged to abstain from
      drinking for the duration of the study. The initial increased levels of both
      hyaluronan (542 +/- 32 ng x ml(-1) serum) and sICAM-1 (488 +/- 70 ng x ml(-1)
      serum), gradually fell during the 6-month observation period, eventually reaching
      values close to those seen in healthy subjects. A positive correlation was
      obtained between changes in these two markers of SEC function/activation on the
      one hand, and between these two tests and bilirubin, on the other hand. These
      data indicate that abnormalities of SEC function/activation, as reflected by
      serum hyaluronan and siCAM-1, are prominent in alcoholic hepatitis, and these
      alterations improve within relatively short periods of time after cessation of
      alcohol consumption.

PMID- 9756048
TI  - Amplitude of visual P3 event-related potential as a phenotypic marker for a
      predisposition to alcoholism: preliminary results from the COGA Project.
      Collaborative Study on the Genetics of Alcoholism.
AB  - Recent data collected at six identical electrophysiological laboratories from the
      large national multisite Collaborative Study on the Genetics of Alcoholism
      provide evidence for considering the P3 amplitude of the event-related potential
      as a phenotypic marker for the risk of alcoholism. The distribution of P3
      amplitude to target stimuli at the Pz electrode in individuals 16 years of age
      and over from 163 randomly ascertained control families (n = 687) was compared
      with those from 219 densely affected alcoholic families (n = 1276) in which three
      directly interviewed first-degree relatives met both DSM-III-R and Feighner
      criteria at the definite level for alcohol dependence (stage II). The control
      sample did not exclude individuals with psychiatric illness or alcoholism to
      obtain incidence rates of psychiatric disorders similar to those of the general
      population. P3 amplitude data from control families was converted to Z-scores,
      and a P3 amplitude beyond 2 SD's below the mean was considered an "abnormal
      trait." When age- and sex-matched distributions of P3 amplitude were compared,
      members of densely affected stage II families were more likely to manifest low P3
      amplitudes (2 SD below the mean) than members of control families, comparing
      affected and unaffected offspring, and all individuals; all comparisons of these
      distributions between groups were significant (p < 0.00001). P3 amplitude means
      were also significantly lower in stage II family members, compared with control
      family members for all comparisons, namely probands, affected and unaffected
      individuals (p < 0.0001), and offspring (p < 0.01). Furthermore, affected
      individuals from stage II families, but not control families, had significantly
      lower P3 amplitudes than unaffected individuals (p < 0.001). Affected males from
      stage II families had significantly lower P3 amplitudes than affected females (p
      < 0.001). Recent linkage analyses indicate that visual P3 amplitude provides a
      biological phenotypic marker that has genetic underpinnings.

PMID- 9756050
TI  - Compliance with treatment and follow-up protocols in project MATCH: predictors
      and relationship to outcome.
AB  - Treatment and follow-up session attendance data from Project MATCH, a multisite
      clinical trial investigating patient-treatment matching, were analyzed to study
      compliance. High rates of compliance to both therapy and research protocols were
      achieved, enhancing treatment integrity and data quality. Strong baseline
      predictors of compliance did not emerge, and the small relationships found were
      consistent with reports from previous studies. Attendance at therapy sessions was
      moderately correlated with research follow-up participation. Treatment compliance
      predicted drinking outcome, underscoring the importance of retaining patients in
      treatment. Future studies should examine the associations between compliance and
      structural features of the treatment environment, treatment delivery, and context
      features that are often under the control of the clinician/investigator.

PMID- 9756051
TI  - Overt behavior problems and serotonergic function in middle childhood among male
      and female offspring of alcoholic fathers.
AB  - A large body of literature indicates that the serotonergic system is involved in
      behavioral regulation, as evidenced by the inverse relationship between impulsive
      aggression and serotonergic function found in adult alcoholics and nonalcoholics.
      However, studies of this relationship among child and adolescent offspring of
      alcoholics (COAs) have not previously been done. This study examines the
      potentially parallel relationship between behavioral dysregulation and low
      serotonergic function in young COAs. The relationship is of potential interest as
      a phenotypic marker of biological vulnerability to aggressiveness, which itself
      has been hypothesized to be a risk factor for later antisocial alcoholism. The
      present work is part of an ongoing prospective study of the development of risk
      for alcohol abuse/dependence and other problematic outcomes in a sample of
      families subtyped by the fathers' alcoholism classification. We examined the
      relationship between overt behavior problems in middle childhood (mean age = 10.5
      +/- 1.7 years) and whole blood serotonin (5-HT) in a subsample of the offspring
      (N = 32 boys and 12 girls). Using a Child Behavior Checklist (CBCL) index of
      behavioral undercontrol, we obtained results indicating that high total behavior
      problem (TBP) children had lower levels of whole blood 5-HT than did low-TBP
      children (p < 0.01). These results support the hypothesis that there is an
      inverse relationship between whole blood serotonin levels and behavior problems
      in young male and female COAs. A father's alcoholism status was not significantly
      related to his child's 5-HT level, i.e., the child's phenotypic expression of
      behavioral dysregulation was more reliably connected to serotonergic function
      than was paternal alcoholism.

PMID- 9756052
TI  - Predicting the development of late-life late-onset drinking problems: a 7-year
      prospective study.
AB  - There has been little empirical study of risk factors for the development of late
      life late-onset drinking problems. In the current prospective study, we compare
      two groups of older adults who, at a baseline assessment, were nonproblem
      drinkers: individuals who developed drinking problems over the course of the next
      7 years (n = 77) and those who did not (n = 197). Late-onset problem drinkers
      reported mild to moderate drinking problems and spontaneous remission rates were
      high. Compared with stable nonproblem drinkers, late-onset problem drinkers at
      baseline were more likely to report incipient problems, heavier alcohol
      consumption, greater friend approval of drinking, more reliance on avoidance
      coping strategies, were more likely to smoke, and were less likely to have acute
      medical conditions that could potentially be complicated by alcohol consumption.
      Contrary to expectation, life stressors did not predict drinking problem onset.
      However, compared with stable nonproblem drinkers, late-onset problem drinkers
      were more likely to have a history of responding to stressors and negative affect
      with increased alcohol consumption.

PMID- 9756053
TI  - Association of alcohol or other drug dependence with alleles of the mu opioid
      receptor gene (OPRM1).
AB  - Opioidergic neurotransmission and, specifically, the mu opioid receptor have been
      implicated in the reinforcing effects of a variety of drugs of abuse.
      Consequently, the present study examined the association of a polymorphic (CA)n
      repeat at the OPRM1 locus (the gene coding for the mu opioid receptor) to alcohol
      or drug dependence in 320 Caucasian and 108 African-American substance-dependent
      or control subjects. Among Caucasians, suggestion of a modest association, which
      could be interpreted as statistically significant (p = 0.03), was observed
      between OPRM1 alleles and substance (alcohol, cocaine, or opioid) dependence.
      Analysis by specific substance showed only a trend level association to alcohol
      dependence. Comparisons among African Americans yielded no evidence for
      association. Further studies of the association between alleles of the OPRM1 gene
      and substance dependence appear warranted, particularly if they use a family
      based approach to control for population stratification. Phenotypes other than a
      broad diagnostic categorization, such as opioid antagonist effects on drinking
      behavior in alcoholics, may provide more consistent evidence of a role for OPRM1
      in behavioral variability.

PMID- 9756054
TI  - Mismatch negativity in young children of alcoholics from high-density families.
AB  - The mismatch negativity (MMN) component of event-related potentials was recorded
      from a group of young children of alcoholics (n = 19, 8 females) with a high
      density family history of alcoholism and from a control group (n = 23, 12
      females), between 8 and 15 years of age. A dichotic listening task was used, and
      subjects had to pay attention to an oddball paradigm in one ear and ignore the
      stimuli in the other ear. The event-related potentials elicited by the standard
      unattended tones were subtracted from those elicited by the infrequent deviant
      unattended tones, and the MMN was measured at 10 frontal and central electrodes.
      No group differences were observed in peak latency, peak amplitude, and mean
      amplitude of the MMN. These results indicated that preattentive mechanisms of
      mismatch detection were not impaired in young subjects at high risk for
      alcoholism. Results are discussed in relation to differences in
      electrophysiological indexes of automatic versus controlled information
      processing and in relation to the characteristics of the sample.

PMID- 9756055
TI  - Effect of recent alcohol intake on parathyroid hormone and mineral metabolism in
      men.
AB  - The mechanisms by which alcohol intake, particularly moderate alcohol intake,
      effects bone metabolism are poorly defined. We have examined the relationship
      between mineral metabolism and recent self-reported alcohol intake (SRAI) across
      a wide range of such intakes in a series of 104 men aged 32 to 78 years of age in
      an outpatient setting. A morning nonfasting urine, serum specimen and recent SRAI
      were obtained from each subject. SRAI was reported as between 0 and 45 oz/week.
      SRAI correlated positively with liver function tests, including serum bilirubin
      (r = 0.30, p = 0.002), alkaline phosphatase (r = 0.30, p = 0.004), and aspartate
      aminotransferase (SGOT) (r = 0.29, p = 0.006). SRAI correlated with serum calcium
      corrected for albumin (r = -0.39, p < 0.001), estradiol (r = 0.43, p < 0.001),
      and immunoreactive parathyroid hormone (iPTH) (r = -0.51, p < 0.001), as well as
      urinary calcium (per 100 mg of creatinine) (r = 0.55, p < 0.001). We have
      arbitrarily divided the participants into two groups on the basis of their
      reported alcohol intake. Individuals in the first group had intakes ranging from
      none to moderate intake (drank 8.4 oz or less of ethanol per week, equivalent to
      an average of two drinks daily or less). Those in the second group had moderate
      or heavier intake, with >8.4 oz of ethanol intake/week. Mean serum iPTH was
      significantly greater in those in the first group (none to moderate), compared
      with the second group (moderate or heavier) (56.0 +/- 3.4 and 39.9 +/- 2.0
      pM/liter, respectively). Calcium corrected for serum albumin was significantly
      greater in individuals in the first, compared with the second, group (9.23 +/-
      0.05 vs. 8.88 +/- 0.07 mg/dl, respectively). In addition, urinary calcium
      (corrected per 100 mg of creatinine) was significantly lower in the former,
      compared with the latter (3.1 +/- 0.4 vs. 8.4 +/- 1.1 mg/100 mg of creatinine,
      respectively). Similarly, urinary excretion of collagen crosslinks (corrected per
      100 mg of creatinine) was significantly less in men in the second group, compared
      with the first group (316 +/- 38 vs. 530 +/- 78 nM/100 mg of creatinine,
      respectively). Not surprisingly, a series of correlations between iPTH and age,
      250-hydroxyvitamin D, and testosterone were significant in individuals with none
      to moderate SRAI, but not moderate or heavier SRAI. Significant independent
      predictors of serum iPTH in the entire group of men were age (beta = 0.215, p =
      0.025), SRAI (beta = -0.281, p = 0.003), 250-hydroxyvitamin D (beta = -0.309, p =
      0.002), and testosterone (beta = -184, p = 0.048). We have concluded that, in
      free-living men, alcohol intake >8.4 oz/week was associated with decreased serum
      iPTH concentrations.

PMID- 9756056
TI  - What makes alcohol-dependent individuals early in abstinence crave for alcohol:
      exposure to the drink, images of drinking, or remembrance of drinks past?
AB  - Craving is a major factor in addiction, predicting poorer outcome to treatment To
      improve our understanding of craving for alcohol, we have compared in the
      laboratory the effects of inducing craving for alcohol by exposure to the sight
      and the smell of an alcoholic beverage, imagery of craving scripts, and recall of
      autobiographical memories of craving. We used subjective measures of craving,
      together with autonomic measures, in 14 abstinent alcohol-dependent individuals
      in the first month after detoxification. All subjects reported a significant
      increase in ratings of urges after exposure to alcoholic drinks, following the
      imagery of craving and after recalling autobiographical memories of craving.
      Physiological measures have shown that craving imagery as well as memory
      induction were equally effective as exposure to alcoholic drinks in modestly
      increasing autonomic arousal (indicated by systolic blood pressure). Our
      preliminary findings support the existing evidence in nicotine and opiate
      dependence that images and memories are as effective as in vivo exposure in
      eliciting craving for drugs.

PMID- 9756057
TI  - Diagnosis and treatment of postoperative chyle leakage via percutaneous
      transabdominal catheterization of the cisterna chyli: a preliminary study.
AB  - PURPOSE: To assess the feasibility of percutaneous transabdominal puncture and
      catheterization of the cisterna chyli or lymphatic ducts (PTCLD) in patients with
      postoperative chyloperitoneum and chylothorax, and to identify and possibly
      embolize the chylous fistula. MATERIALS AND METHODS: Five patients had
      postoperative uncontrolled chyle fistulas. Two patients with chylothorax had
      thoracic duct (TD) ligation after esophagectomy and neck surgery. The other three
      patients had chylous ascites after surgery of the pancreas, the aorta, and the
      esophagus, respectively. After lymphographic opacification, the cisterna chyli
      (CC) or retroperitoneal lymph ducts were punctured transabdominally with a 21
      gauge needle and catheterized with a 3-F catheter to reach the TD if possible.
      Microcoils were used to embolize a TD laceration. RESULTS: Lymph ducts as small
      as 2-3 mm were catheterized successfully in three patients. The TD was
      catheterized in two patients; one TD fistula was embolized with cure of
      chylothorax. In one patient with a surgically tied TD, duct occlusion was
      confirmed despite continued pleural effusion. Three fistulas, not seen with
      lymphography, were identified in two of three chylous ascites and one
      chylothorax. There was no morbidity. As a result of this procedure, four of five
      patients did not require repeated operation. CONCLUSIONS: PTCLD in the study of
      chyle fistulas was feasible and safe in the management of five patients and
      clinically useful in four patients; transabdominal catheter lymphography with
      aqueous contrast medium is more sensitive than pedal lymphography. Further
      evaluation is necessary.

PMID- 9756059
TI  - Successful treatment of renal transplant ureter stenosis with use of the biliary
      Z stent.

PMID- 9756058
TI  - Real-time CT-fluoroscopy for guidance of percutaneous drainage procedures.

PMID- 9756060
TI  - Percutaneous transvesical drainage of a seminal vesicle abscess.

PMID- 9756061
TI  - Percutaneous embolotherapy of lower gastrointestinal hemorrhage.
AB  - PURPOSE: To evaluate percutaneous embolotherapy in the treatment of lower
      gastrointestinal hemorrhage. MATERIALS AND METHODS: Twenty-one patients who
      underwent attempted percutaneous embolization for acute lower gastrointestinal
      bleeding between 1982 and 1997 were retrospectively studied. Hemorrhagic sites
      included jejunum (n = 4), ileum (n = 4), cecum (n = 4), and the remaining colon
      (n = 9). RESULTS: Embolization was not technically possible in four patients
      (19%). Hemostasis was achieved in 15 patients (71%) with prolonged hemostasis in
      10 (48%). All embolizations distal to the cecum resulted in prolonged hemostasis.
      Three of four patients with jejunal bleeding had recurrent bleeding after
      apparent successful embolization. Only one of four cecal embolizations achieved
      prolonged cessation of bleeding. No ischemic complications were identified.
      CONCLUSION: Based on these data, it would appear that the risk of bowel
      ischemia/infarction in the lower gastrointestinal tract may not be as high as has
      been suggested. Two regions (cecum and proximal jejunum) were associated with
      poor results, suggesting these areas may not be as responsive to embolotherapy as
      other sites in the lower gastrointestinal tract.

PMID- 9756062
TI  - Superselective coil embolization in acute gastrointestinal hemorrhage: personal
      experience in 10 patients and review of the literature.
AB  - PURPOSE: To evaluate the safety and efficiency of microcoil embolization in upper
      and lower gastrointestinal hemorrhage. PATIENTS AND METHODS: Superselective
      microcoil embolization was performed in 10 patients (upper gastrointestinal
      bleeding, n = 3; lower gastrointestinal bleeding, n = 7) who had acute
      gastrointestinal hemorrhage. Embolization was performed as peripherally as
      possible with use of coaxial catheter systems. Embolization materials included
      microcoils (2-4 mm) alone (n = 5), microcoils and polyvinyl alcohol particles
      (355-500 microm) (n = 4), and microcoils and gelatin sponge particles (n = 1).
      RESULTS: Immediate hemostasis was achieved in eight patients. In two patients
      with dual blood supply of the bleeding site, significant reduction of hemorrhage
      resulted. In these two patients, it was technically impossible to place the
      coaxial catheter distally enough to allow safe embolization of both feeding
      vessels. No clinical signs of ischemia or infarction were observed after
      intervention. CONCLUSION: Microcoil embolization is a safe and efficient
      procedure for controlling acute lower gastrointestinal bleeding if performed in a
      superselective catheter position. In upper gastrointestinal bleeding, microcoil
      embolization is an established treatment and can be performed more proximally.

PMID- 9756063
TI  - Comparison of early deflation rate of detachable latex and silicone balloons and
      observations on persistent varicocele.
AB  - PURPOSE: To determine the frequency of and time until spontaneous deflation of
      detachable embolization balloons made of different materials and the correlation
      between persisting or recurrent varicocele and the spontaneous deflation of the
      balloons. MATERIALS AND METHODS: Forty-five patients with clinically detected
      left-sided varicocele underwent embolization with 78 silicone and 22 latex
      balloons. The minimum follow-up time was 3 months and the follow-up consisted of
      clinical examination, color duplex ultrasonography, and plain radiography of the
      balloons. Those patients who were suspected of having recurrent varicoceles
      underwent control venography to assess the internal spermatic vein. RESULTS: All
      of the latex balloons and 10% of the silicone balloons deflated spontaneously
      during the follow-up. The average time until deflation was 5.1 months for latex
      and 9.9 months for silicone balloons. Persistence of varicocele, attributed to
      perfusion through a previously occluded portion of the internal spermatic vein,
      occurred in two of 11 (18%) recurrences. Nine of 11 (72%) recurrences were due to
      bypassing collaterals past the site of detachable balloon placement. CONCLUSIONS:
      Latex balloons seem to predispose more to persisting/recurrent varicocele than
      silicone balloons. Early deflation of the balloons explained two (18%) of the 11
      persisting or recurrent varicoceles. A combination of a sclerosing agent with
      balloon embolization of the internal spermatic vein is recommended.

PMID- 9756064
TI  - Single institution prospective evaluation of the over-the-wire Greenfield vena
      caval filter.
AB  - PURPOSE: To assess the technical and clinical success of the over-the-wire (OTW)
      Greenfield inferior vena caval (IVC) filter. MATERIALS AND METHODS: Prospective
      evaluation of the OTW Greenfield filter in 47 patients was performed during the
      course of 18 months. Technical success and deployment problems were documented.
      Caval perforation, leg asymmetry, and tilt were evaluated with a postprocedure,
      noncontrast computed tomographic (CT) scan. Follow-up was performed at 6- and 12
      month intervals after the procedure and included a clinical history, chart
      review, and magnetic resonance (MR) imaging examination of the IVC. RESULTS:
      Ninety-one percent of filters were placed without technical difficulties and 100%
      were successfully deployed. Technical difficulties included sheath kinking prior
      to deployment (n = 3), initial incomplete filter opening (n = 1), and wire
      entrapment within the filter (n = 1). Of 38 patients evaluated with CT, there was
      no case of caval perforation. Twenty-one patients (55%) demonstrated tilt and 14
      (37%) had leg asymmetry. Tilting occurred more frequently when the filter was
      placed from a femoral approach (51%) than from a jugular approach (12%). Of
      patients with leg asymmetry, the vena cava was narrow in anteroposterior (AP)
      dimension in five (36%). Of 13 deaths, none were attributed to pulmonary
      embolism. One patient (2%) had a recurrent pulmonary embolus. Two of 16 patients
      (12%) with MR imaging follow-up had documented IVC thrombosis. CONCLUSIONS: The
      OTW Greenfield filter has an effective delivery system, with few difficulties
      encountered during deployment. Filter tilt and leg asymmetry are common. The
      etiology of leg asymmetry is likely multifactorial but is often associated with a
      cava with a small AP diameter. Because OTW deployment appears to offer no benefit
      in centering the filter, the authors have elected to remove the wire prior to
      filter deployment to avoid possible entanglement. MR imaging follow-up reveals an
      acceptable incidence of IVC thrombosis.

PMID- 9756065
TI  - Clinical experience with the antecubital Simon nitinol IVC filter.
AB  - PURPOSE: To evaluate the Simon nitinol vena cava filter (SNF) placed via the
      antecubital vein in a series of patients. Issues examined by the authors included
      insertion site variables, filter efficacy, and complications. The authors also
      explored the option of placement of a peripherally inserted central catheter
      (PICC) via the same access site. MATERIALS AND METHODS: This was a prospective
      study that included all patients who had undergone antecubital attempt at
      insertion of the SNF. Seventy-four consecutive patients were enrolled during a 29
      month period. A PICC was inserted concomitantly in 23 of these patients. The
      series included 38 men and 36 women, with a mean age of 62.5 years (range, 17-88
      years). The clinical indications for filter placement included contraindication
      to anticoagulation (81.1%), complication of anticoagulation (9.4%), failure of
      anticoagulation (8.1%), and prophylactic placement (1.4%). Concomitant PICCs were
      inserted for chemotherapy (56.5%), venous access (39.1%), and total parenteral
      nutrition (4.4%). Clinical follow-up was available in 61 patients. Mean follow-up
      was 124 days (range, 0-884 days). RESULTS: The SNF was successfully placed via
      the antecubital vein in 98.6% of the patients. In one patient, access was via the
      right common femoral vein because of failed right arm access. There was a
      question of pulmonary embolism (PE) after filter placement in two patients.
      Otherwise, there were no complications related to placement of either the filter
      or PICC. CONCLUSION: Antecubital venous insertion of the SNF is a safe and
      effective method for the prevention of PE in patients who cannot be managed with
      traditional anticoagulation, and offers the option of inserting a PICC with no
      added complications.

PMID- 9756066
TI  - Autogenous vein-covered stent for the endovascular management of a superior
      mesenteric artery pseudoaneurysm.

PMID- 9756067
TI  - Blunt traumatic injury to the superior mesenteric artery and celiac axis.

PMID- 9756068
TI  - In vitro evaluation of the relative thrombolytic efficiency of forced
      intrathrombic injections: saline versus urokinase.
AB  - PURPOSE: To compare the rates of thrombolysis produced by forced intrathrombic
      injections of saline versus urokinase, as well as automated versus manual
      injections of urokinase, with use of an in vitro model of a vascular occlusion.
      MATERIALS AND METHODS: The rates of thrombolysis produced by forced intrathrombic
      injections of saline and urokinase were compared in an in vitro radiometric model
      utilizing I-125-labeled thrombus. Similar experiments were performed to compare
      manual and automated injections of urokinase. The dissolution of the thrombus was
      quantitatively monitored with use of a scintillation detector. Averaged time
      activity data for each type of experiment were fit to exponential functions and
      half times of lysis calculated. The differences in the half times for the
      experiments being compared were evaluated for significance with use of the
      Student t test. RESULTS: The half times of lysis produced by forced intrathrombic
      injections of urokinase were substantially and significantly shorter than those
      produced by forced saline injections. The half time of lysis produced by
      automated injections was not significantly different than that produced by manual
      injections. CONCLUSIONS: Forced intrathrombic injections of urokinase produce
      faster and substantially more thrombolysis when compared with similarly
      administered saline. Also, for forced intrathrombic injections of lytic agents,
      an automated injector is an equivalent alternative to manual injections.

PMID- 9756069
TI  - New thrombolytic brush catheter in thrombosed polytetrafluoroethylene dialysis
      grafts: preclinical animal study.
AB  - PURPOSE: To assess the safety, efficacy, endothelial changes, and risks of
      pulmonary embolic events after the use of a new thrombolytic brush catheter in
      mature thrombosed polytetrafluoroethylene (PTFE) dialysis grafts in an animal
      model. MATERIALS AND METHODS: Loop configuration PTFE grafts were implanted in
      the femoral vessels of 12 canines 4 weeks before mechanical thrombosis was
      performed. The thrombus was allowed to consolidate for 24 hours in 10 animals, 72
      hours in one animal, and 7 days in one animal. Standard percutaneous criss-cross
      catheter access was performed, and a soft, low-speed, brush (6 mm in diameter),
      aided by 250,000 U of periprocedural urokinase, was utilized for thrombolysis.
      The native vessels, just distal to the anastomosis, and lungs were evaluated
      macro- and microscopically. RESULTS: Thrombolysis was complete in all grafts with
      the exception of a small segment between the crossing of the access vascular
      sheaths. The total thrombolysis time ranged from 8 to 12 minutes; this included 5
      minutes of pulse-spray lacing. No difference in thrombolysis time was found with
      regard to the age or amount of thrombus. Minimal endothelial changes were noted
      and no evidence of acute pulmonary embolus was found on necropsy or histologic
      studies. CONCLUSION: This method offers a simple, safe, and efficient means of
      recanalization of thrombosed PTFE dialysis grafts in this canine model.

PMID- 9756070
TI  - Phantom for calibration of preoperative imaging modalities in endoluminal stent
      graft repair of aortic aneurysms.
AB  - PURPOSE: Successful deployment of an endoluminal prosthesis for repair of an
      abdominal aortic aneurysm (AAA) is critically dependent on accurate preoperative
      assessment of aneurysm morphology with use of such modalities as contrast
      aortography (CA), spiral computed tomography (CT), magnetic resonance (MR)
      imaging, and intravascular ultrasonography (IVUWS). The authors describe a new
      phantom that could be used both to calibrate these four imaging modalities and to
      determine which imaging technique(s) is (are) best for preoperative AAA sizing.
      MATERIALS AND METHODS: A life-sized AAA model was constructed of silicone
      elastomers with luminal access ports for introduction of contrast media and
      catheters. Contrast material-filled rings were positioned circumferentially along
      the length of the model as reference points for dimension measurements. The
      modalities were compared to each other relative to the actual dimensions of the
      model, as determined at its construction. RESULTS: In this pilot study, all
      modalities were relatively similar in their ability to measure the dimensions of
      the AAA model. Length measurements accounted for most of the interinstitutional
      and interobserver variability. MR imaging had the least variability. CONCLUSIONS:
      The authors developed a new phantom that can be imaged successfully with CA, CT,
      MR imaging, and IVUS in repetitive, reproducible fashion. Structural refinements
      and future larger scale, statistically significant evaluations of such models
      should establish this as a useful adjunct in multicenter endoluminal stent-graft
      trials to allow calibration of imaging modalities and to determine which modality
      or modalities is (are) best for preoperative AAA sizing.

PMID- 9756071
TI  - Effect of iodinated contrast media on neutrophil adhesion to cultured endothelial
      cells.
AB  - PURPOSE: To investigate the influence of contrast media (CM) on endothelial cells
      (ECs) with respect to cytotoxicity and to neutrophil adhesion. MATERIALS AND
      METHODS: Human umbilical vein ECs were incubated with chromium-51-labeled human
      neutrophils in the presence of CM (diatrizoate, ioxaglate, iopamidol, and
      iodixanol) in three concentrations: 2, 20, and 50 mg I/mL. CM was compared with
      glucose solutions prepared from plain, buffered glucose solutions, iso-osmolar to
      the corresponding CM solution. Neutrophil adhesion to the EC monolayer, EC
      morphology, and cytotoxicity were evaluated. RESULTS: The effect of CM on
      neutrophil adhesion was dependent on dose, with increased adhesion at low CM
      concentrations (2 and 20 mg I/mL) and decreased adhesion at high CM concentration
      (50 mg I/mL). The response was observed only if ECs and neutrophils were exposed
      to CM simultaneously in a shared environment. Glucose solutions with the same
      osmolarity did not show similar effect. Both diatrizoate and ioxaglate had a
      greater cytotoxic effect on ECs and neutrophils than did iodixanol and iopamidol.
      CONCLUSION: The altered neutrophil adhesion to ECs may be due to CM-induced
      cytotoxicity or CM-induced EC activation because the glucose solutions did not
      cause a similar change at equal osmolality. The lack of cell death, combined with
      altered neutrophil adhesion implies modulation of cell adhesion molecules by CM.
      The results could be pertinent to the pathogenesis of peripheral vascular lesions
      and the endothelial response in immunosuppressed or septic patients receiving CM
      during imaging studies.

PMID- 9756072
TI  - Single-specimen bile cytology: a prospective study of 80 patients with
      obstructive jaundice.
AB  - PURPOSE: To determine the sensitivity, specificity, and charges associated with
      single-specimen bile cytologic study in patients with obstructive jaundice.
      MATERIALS AND METHODS: Eighty consecutive patients with presumed malignant
      biliary strictures underwent percutaneous biliary drainage (PBD). Cytologic
      evaluation was performed on a single bile specimen from each patient collected at
      the time of the PBD. Final diagnoses were obtained from either percutaneous (n =
      14) or surgical (n = 66) histologic specimens (gold standard). Both data sets
      were then compared to determine the sensitivity and specificity of bile cytology.
      The charges associated with bile cytodiagnosis were compared to those for other
      biopsy procedures utilized in the same setting. RESULTS: Eighty bile specimens
      were obtained with a mean of 14 mL (range, 3-65 mL) per patient with 79 (99%)
      specimens adequate for cytologic processing. Eleven (13%) specimens were
      acellular. The overall sensitivity was 15% and specificity was 100%; these values
      were not dependent on the volume of the bile specimen (P > .10) or type of
      malignancy (P = .10). For bile cytodiagnosis, the mean charge was $160 and the
      successful biopsy rate (true-positive plus true-negative results/total number
      procedures) was 27%. CONCLUSION: Single-specimen bile cytology has a low
      sensitivity; however, because of its convenience, simplicity, atraumatic nature,
      and low relative charge versus comparable procedures, it may be useful as an
      adjunct to PBD in patients with suspected malignant biliary disease.

PMID- 9756073
TI  - Particle embolization for hepatocellular carcinoma.
AB  - PURPOSE: To evaluate the outcome of all patients undergoing particle embolization
      for hepatocellular carcinoma at a single institution from January 1, 1993,
      through December 31, 1995. MATERIALS AND METHODS: The charts and radiographs of
      all patients undergoing particle embolization during the study period were
      reviewed. The following information was collected: patient demographics, Child
      class and Okuda stage, number of embolization treatment sessions, length of
      hospital stay, complications related to the embolization procedure, including
      postembolization syndrome, current patient status, and date of death. RESULTS:
      Forty-six patients underwent 86 embolization sessions during the study period.
      Postembolization syndrome developed after 70 of the 86 sessions (81%); in four
      cases (4.6%) this required treatment that extended the patient's hospital stay.
      Three other complications occurred (3.5%), including a splenic infarct and two
      episodes of transient hepatic failure, all treated supportively. There was one
      death within 30 days, but it was not directly attributable to embolotherapy.
      Follow-up was available for all of the patients who underwent treatment. Thirty
      four patients were classified as Child class A, and 12 were classified as Child
      class B. Thirty patients were classified as Okuda stage I, 14 were classified as
      Okuda stage II, and two were classified as Okuda stage III. Overall actuarial
      survival was 50% at 1 year and 33% at 2 years. There was a statistically
      significant difference in survival between Okuda stage I and stage II patients,
      but not between Child class A and class B patients. CONCLUSION: Particle
      embolization for hepatocellular carcinoma is well tolerated and demonstrates
      actuarial survival of 50% at 1 year and 33% at 2 years.

PMID- 9756074
TI  - Pediatric transvenous liver biopsy.

PMID- 9756075
TI  - Thrombosed dialysis grafts: percutaneous mechanical declotting using a central
      venous approach.

PMID- 9756076
TI  - Puncture-induced deformity of a metallic stent within a dialysis access graft
      causing thrombotic failure: case report and description of salvage.

PMID- 9756077
TI  - Endovascular interventional MR: balloon angioplasty in a hemodialysis access flow
      phantom [corrected].

PMID- 9756078
TI  - Stent placement in a carotid artery bypass graft in a patient with Takayasu
      arteritis.

PMID- 9756079
TI  - Thromboaspiration to treat inadvertent arterial emboli during dialysis graft
      declotting.

PMID- 9756080
TI  - Percutaneous transthoracic needle biopsy: a difference in definitions and
      calculation of diagnostic yield.

PMID- 9756081
TI  - Iliofemoral venous thrombolysis after failed surgical thrombectomy.

PMID- 9756082
TI  - Wedged hepatic venography with biplane digital subtraction imaging to facilitate
      accessing the portal venous system for TIPS.

PMID- 9756083
TI  - US-guided puncture of the internal jugular vein: an unexpected anatomic
      relationship.

PMID- 9756084
TI  - Treatment of malignant ureteric stricture with use of a Vascucoil spring stent.

PMID- 9756085
TI  - Extravasation from power injection near previous arteriotomy site: a case for
      caution.

PMID- 9756086
TI  - Thematic review series II: vasopressin: genes, receptors, water channels, and
      antagonists. Introduction.

PMID- 9756087
TI  - Vasopressin processing defects in the Brattleboro rat: implications for
      hereditary central diabetes insipidus in humans?
AB  - The arginine vasopressin (AVP) precursor gene of mammals contains three exons
      encoding the principal domains of the polyprotein precursor, including
      vasopressin (exon A), neurophysin (exon B), and glycopeptide (exon C). The AVP
      precursor (preprohormone) is processed and transported through the endoplasmic
      reticulum (ER), Golgi apparatus, and secretory vesicles, and finally, mature AVP
      is secreted from the posterior pituitary into the circulation. The exact steps of
      these processes during AVP translation and posttranslation events are not yet
      well elucidated. Defects in peptide processing are associated with several
      genetic disorders, including central diabetes insipidus (CDI). In the Brattleboro
      rat with CDI, the mRNA and protein of AVP are present in the hypothalamus, but no
      circulating AVP is detectable, thus suggesting a processing defect, transport
      defect, or both. The mutated AVP gene precursor of Brattleboro rat has a deletion
      of a single base, guanine, in the neurophysin coding region that leads to a
      frameshift resulting in the loss of the normal stop codon. It has been reported
      that the mutated precursor is trapped in the ER and does not reach the Golgi
      apparatus. Recent studies examined AVP secretion in cultured COS cells
      transfected with various constructs from wild-type and mutated Brattleboro AVP
      gene precursors. The wild-type in vitro studies demonstrated that intact
      neurophysin, but not the glycoprotein coding region, is necessary for normal AVP
      processing and secretion. Next, the results demonstrated that the guanine defect
      in the neurophysin coding region and the prolonged C-terminus accounted for the
      processing defect in the Brattleboro rat with CDI. These defects no doubt impair
      the folding and configuration necessary for normal processing of the AVP gene
      precursor in the ER. In hereditary CDI in humans, the majority of the mutations
      have also been shown to occur in the neurophysin coding region. However, in
      contrast to the recessive defect in the Brattleboro rat, in human CDI,
      neurotoxicity and denigration of the magnocellular neurons have been observed,
      and dominant inheritance occurs. Moreover, all mutations are missense, nonsense,
      or deletions in human CDI rather than the shift in reading frame and preserved
      neurons that is observed with the Brattleboro rat. Thus, the results from studies
      in the Brattleboro rat may only be partially applicable to hereditary CDI in
      humans.

PMID- 9756088
TI  - Vasopressin receptor mutations causing nephrogenic diabetes insipidus.
AB  - In congenital nephrogenic diabetes insipidus, the renal collecting ducts are
      resistant to the antidiuretic action of arginine vasopressin or to its
      antidiuretic analog 1-deamino[8-D-arginine] vasopressin (dDAVP). This is a rare,
      but now well described entity secondary to either mutations in the AVPR2 gene
      that codes for the vasopressin antidiuretic (V2) receptor or to mutations in the
      AQP2 gene that codes for the vasopressin-dependent water channel. A majority (>
      90%) of congenital nephrogenic diabetes insipidus patients have AVPR2 mutations:
      Of 115 families with congenital nephrogenic diabetes insipidus, 105 families had
      AVPR2 mutations, and 10 had AQP2 mutations. When studied in vitro, most AVPR2
      mutations lead to receptors that are trapped intracellularly and are unable to
      reach the plasma membrane. A minority of the mutant receptors reach the cell
      surface but are unable to bind vasopressin or to trigger an intracellular
      adenosine 3:5-cyclic phosphate signal properly. Most of the reported mutations
      are secondary to a complete loss of function of the receptor, and only a few
      mutations have been associated with a mild phenotype. These advances provide
      diagnostic tools for physicians caring for these patients because, when the
      disease causing mutation has been identified, carrier and perinatal testing could
      be done by mutation analysis.

PMID- 9756089
TI  - Aquaporin-2 water channel mutations causing nephrogenic diabetes insipidus.
AB  - Since the discovery of aquaporin water channels, insight into the molecular
      mechanism by which rapid osmotic water occurs across cell membranes has greatly
      improved. Aquaporin-2 is the vasopressin-responsive water channel in the
      collecting duct, and vasopressin control of water permeability in the collecting
      duct occurs in two ways: a short-term regulation and a long-term adaptation. In
      congenital nephrogenic diabetes insipidus, the kidney does not respond to
      vasopressin. Ninety percent of these patients carry a mutation in the gene coding
      for the vasopressin V2 receptor located on the X chromosome. Autosomal recessive
      and dominant forms of nephrogenic diabetes insipidus that are caused by mutations
      in the aquaporin-2 gene have now been described. This review focuses on recent
      insight in the molecular and cellular defect in autosomal nephrogenic diabetes
      insipidus.

PMID- 9756090
TI  - Disordered water channel expression and distribution in acquired nephrogenic
      diabetes insipidus.
AB  - A series of recent studies have demonstrated that expression of aquaporin-2
      (AQP2), the vasopressin-regulated water channel of the kidney collecting duct, is
      greatly reduced in acquired forms of nephrogenic diabetes insipidus (NDI). In
      some forms of NDI, there is also impaired delivery of these channels to the
      apical plasma membrane, where they permit water reabsorption from the urine. The
      combination of these factors is likely to underlie the urinary concentrating
      defect that defines these conditions. Direct infusion of vasopressin causes an
      increase in AQP2 expression, probably via a rise in cytosolic adenosine 3:5
      cyclic phosphate, which also acts as the second messenger, triggering the
      delivery of AQP2 to the plasma membrane. However, it is clear from the studies
      described that there are also vasopressin-independent pathways that regulate the
      expression of AQP2, some of which appear to reflect intranephric changes, whereas
      others involve systemic signals. These studies also show that recovery of AQP2
      expression, even after correction of the underlying condition, can be slow,
      consistent with the clinical observation that recovery of urinary-concentrating
      ability often takes weeks or months. An understanding of the cellular signals and
      mechanisms responsible for the decrease in AQP2 expression may make it possible
      to develop treatments for this common clinical problem.

PMID- 9756091
TI  - Vasopressin release, water channels, and vasopressin antagonism in cardiac
      failure, cirrhosis, and pregnancy.
AB  - Vasopressin (AVP) is released in response to both osmotic and nonosmotic stimuli.
      Nonosmotic-stimulated AVP release occurs in cardiac failure, cirrhosis, and
      pregnancy in response to alterations in arterial circulatory integrity. Cardiac
      failure in rats is associated with increased plasma AVP and hypothalamic AVP
      mRNA, and in humans, it is associated with cardiac failure. Plasma AVP
      concentrations are elevated when measured with a sensitive radioimmunoassay.
      Urinary concentrations of AVP-responsive aquaporin-2 water channels are also
      elevated in cardiac failure. V2 receptor antagonists correct the impaired solute
      free water excretion seen in rats with low-output cardiac failure and reverse the
      upregulation of renal aquaporin-2 water channels. Orally active non-peptide
      selective V2 receptor antagonists administered to patients with congestive
      cardiac failure decrease urinary concentrations of aquaporin-2, increase solute
      free water clearance, and correct the hyponatremia. Cirrhosis of the liver
      results in splanchnic arterial vasodilation and increased vascular capacity, most
      likely secondary to increased nitric oxide production. This relative underfilling
      of the arterial circulation stimulates nonosmotic AVP release with resultant
      water retention. Aquaporin-2 gene expression is upregulated in the kidneys of
      rats with cirrhosis of the liver. AVP-2 receptor antagonists administered to
      animals with cirrhosis reverse the water retention. Human studies using orally
      active, non-peptide-selective V2 receptor antagonists in patients with cirrhosis
      are currently underway. Pregnancy is another state of nitric oxide-mediated
      arterial vasodilation that is associated with plasma AVP concentrations that are
      relatively high for the degree of hypoosmolality. Upregulation of the water
      channel aquaporin-2 in the renal papillae of pregnant rats has also been
      demonstrated, and this effect is reversed by administration of a V2 receptor
      antagonist.

PMID- 9756092
TI  - Angiotensin II and bradykinin regulate the expression of P-selectin on the
      surface of endothelial cells in culture.
AB  - Cell-surface expression of endothelial P-selectin increases adhesion and
      migration of leukocytes and thus may participate in the pathogenesis of
      reperfusion injury and atherosclerosis. Angiotensin II (Ang II) is also thought
      to be involved in such disease states. Nitric oxide (NO) downregulates P-selectin
      expression, and bradykinin (BK) is known to stimulate NO release from endothelial
      cells. The objective of this study was to determine the effects of 10-min
      stimulation of cultured human umbilical endothelial cells (HUVECs) with Ang II,
      BK, or both on P-selectin expression. Ang II (10(-9)-10(-5) M) stimulated P
      selectin expression in a concentration-dependent manner, exhibiting a significant
      effect at 10(-7) M and reaching a plateau at 5 x 10(-5) M. Pretreatment of HUVECs
      with the AT1 antagonist losartan and the AT1/AT2 antagonist saralasin but not the
      AT2 antagonist PD123319 (all at 10(-5) M) markedly attenuated the effect of 10(
      7) M Ang II. The effects of Ang II on P-selectin expression were not affected by
      the presence of the NO synthase inhibitor nitro-L-arginine (L-NA, 5 x 10(-4) M)
      but were abolished by pretreatment with superoxide dismutase (SOD). BK (10(-6) M)
      abolished the effects of 10(-7) M Ang II on P-selectin expression but did not
      affect P-selectin expression induced by desmopressin (0.01-10 microM). L-NA
      obliterated the blunting effect of BK on the Ang II-induced P-selectin membrane
      expression. BK alone slightly stimulated P-selectin expression, but in the
      presence of L-NA, BK markedly enhanced P-selectin expression. The effects of BK
      in the presence of NA were not altered by SOD, indicating that at difference with
      Ang II, it acts by a mechanism other than superoxide generation. Thus, Ang II
      acting on AT1 receptors stimulates superoxide generation, which, in turn, induces
      expression of P-selectin on the endothelial cell surface. BK inhibits the effects
      of Ang II, likely acting via NO. We conclude that the balance between Ang II, BK,
      and NO can regulate P-selectin expression on the endothelial cell membrane, an
      important component of the cascade leading to leukocyte adhesion to the vascular
      endothelium.

PMID- 9756093
TI  - Streptozotocin, an analog of N-acetylglucosamine, blocks the removal of O-GlcNAc
      from intracellular proteins.
AB  - Streptozotocin (STZ), an analog of N-acetylglucosamine (GlcNAc), is a specific
      toxin for the pancreatic beta cell. We found that treatment of rats with STZ
      results in an early beta-cell-specific increase in the level of intracellular
      protein modification by O-linked GlcNAc (O-GlcNAc). Using a model O-GlcNAc
      peptide based on the transcription factor Sp1, we show that treatment of cultured
      cells with STZ during peptide biosynthesis results in hyperglycosylation of the
      peptide as a result of the ability of STZ to specifically inhibit the activity of
      O-GlcNAc-selective N-acetyl-beta-D-glucosaminidase. Although this inhibitory
      activity of STZ probably can occur in all cells, we found, using in situ
      hybridization, that beta cells express very high levels of the mRNA encoding the
      enzyme responsible for cytoplasmic protein O-glycosylation, O-GlcNAc transferase
      (OGT). These findings suggest that the pancreatic beta cell is particularly
      sensitive to the toxicity of STZ because it expresses such high levels of OGT.
      When STZ blocks O-GlcNAc removal from intracellular proteins, the cell with the
      most rapid on-rate for O-GlcNAc, the beta cell, will experience the most rapid
      accumulation of this protein modification. Because we also show that the on-rate
      of O-GlcNAc is substrate driven in several cell types, we speculate that the beta
      cell, with its high level of OGT, may also respond to elevations of blood sugar
      with increased protein modification by O-GlcNAc. Thus, this proposed mechanism of
      STZ toxicity on the beta cell may result from an exaggeration of a heretofore
      unrecognized physiological response to glucose mediated through the high level of
      OGT in these cells.

PMID- 9756094
TI  - Presidential address: meeting the challenge of change.

PMID- 9756095
TI  - Presentation of the 1998 Kober Medal to Eugene Braunwald.

PMID- 9756096
TI  - Morphogenesis of the hypothalamus and hypophysis: their association, dissociation
      and reassociation before and after "Rathke".
AB  - Recent progress in the experimental morphology of the development of amphibian
      pituitary gland is reviewed. A series of transplantation experiments were carried
      out using wild-type embryos of the toad as a donor and albino embryos as a
      recipient. Melanin granules in the wild-type cells allowed tracing of the
      developmental fate of the grafts as a visible cell marker. These studies have
      demonstrated that the pituitary gland is not a stomodeal derivative, as it has
      long been believed to be under the name of "Rathke's pouch". The adenohypophysis
      is of neural origin. The anterior part of the neural ridge (ANR) in the
      neuroectoderm of the open neurula gives rise to the whole adenohypophysis, i. e.,
      pars distatis, pars intermedia and pars tuberalis. The presumptive hypothalamus
      is apposed caudally to the pituitary primordium. A part of the ANR contributes
      neurons to the preoptic hypothalamus even after closure of the neural tube. The
      anlagen of the olfactory system, which include the nasal epithelia and the
      olfactory bulbs, are situated on both sides of the pituitary primordium in the
      neural ridge. In both hypothalamic-hypophyseal and olfactory systems, the
      peripheral and central parts derive from closely affiliated cell populations,
      suggesting their clonal relationships. Development of the hypophysis and
      hypothalamus is interdependent. On one hand, a connection with the embryonic
      hypothalamus is essential for the pituitary proopiomelanocortin cells to develop.
      On the other hand, neither the hypothalamic median eminence nor its axonal supply
      develops without the presence of the pituitary primordium. Novel aspects of the
      ontogeny and phylogeny of these organs are discussed with special reference to
      the role of the neural ridge in the generation of a spectrum of chemoreceptive
      organs.

PMID- 9756097
TI  - Immunoelectron microscopic identification of lysozyme-expressing cells in human
      labial salivary glands.
AB  - Although human labial gland secretions contain serous components such as the
      bactericidal enzyme, lysozyme, the presence of serous cells in this gland has yet
      to be clearly visualized under the electron microscope. The present study
      identifies lysozyme-expressing cells of the labial glands using microwave-fixed,
      Epon-Araldite-embedded specimens, which showed excellent preservation of both
      ultrastructural detail and antigenicity for post-embedding immunogold labeling of
      lysozyme. Ultrastructurally, all of the secretory cells of the glands appeared to
      be a mucous-type and have a serial maturation relationship, consistent with a
      previous report by TANDLER et al. (1969a): their secretory granules were electron
      lucent and exhibited reactivity for mucus staining by the periodic acid
      thiocarbohydrazide-silver proteinate (PA-TCH-SP) method. We classified them into
      two immature types (I, II) and two mature types (I, II). Their distinctive
      features were the following: 1) relatively small (0.5-1 microm) secretory
      granules and well-developed basal rough endoplasmic reticulum for the immature
      types; 2) larger (1-2 microm) secretory granules and well-developed Golgi
      apparatus, which showed intense PA-TCH-SP reactivity in the 2-3 trans-cisterns,
      for the mature types; 3) few secretory granules in the immature type I; and 4)
      the darkest appearance for the mature type II. Immunogold labeling with anti
      lysozyme showed specific labeling of the two immature-type cells, in which gold
      particles were found mainly over the secretory granules and Golgi apparatus, and
      moderately over the rough endoplasmic reticulum. In the secretory granules, the
      labeling was distributed throughout the contents and was present even if they
      showed strong PA-TCH-SP reactivity; in the Golgi area, it was seen over the
      stacked cisternae, trans-Golgi networks, and condensing vacuoles. No specific
      labeling was seen in the mature-type cells or in the duct cells. These immature-
      and mature-type cells were almost equivalent to the "serous demilune or acinus"
      and "mucous tubule" cells, respectively, at the light-microscopic level. These
      results indicate that the traditional "immature mucous-type cells" of the human
      labial glands produce lysozyme and should be classified as seromucous cells.

PMID- 9756099
TI  - Localization of cytoplasmic free calcium ions in PC12 cells with varicose fibers.
AB  - Differentiated PC12 cells with varicose fibers were used as a model of
      sympathetic neurons to demonstrate the intracellular localization of cytoplasmic
      free calcium ions. Changes in the concentration of cytoplasmic free calcium ions
      were analyzed at individual varicosities upon stimulation with acetylcholine by
      laser scanning confocal microscopy. Transient increases in cytoplasmic free
      calcium ion concentration were localized in the varicosities and recognized in
      both the absence and presence of extracellular Ca2+. Immunocytochemical analysis
      of intracellular calcium channels, 1, 4, 5-trisphosphate receptors and ryanodine
      receptors, by electron microscopy demonstrated that immunoreactive sites were
      mainly localized in large dense core vesicles in the varicosities and neurites.
      These results suggest that the exocytosis of large dense core vesicles is
      regulated by an increase in cytoplasmic free calcium ion concentration from an
      intracellular Ca2+ store.

PMID- 9756098
TI  - Identification of arterial and venous segments of blood vessels using alkaline
      phosphatase staining of ink/gelatin injected tissues.
AB  - The present study describes a method for discriminating between the arterial and
      venous segments of blood vessels in mouse tissues and organs using alkaline
      phosphatase (ALPase) staining of ink/gelatin injected tissues. Anesthetized mice
      were injected through the left ventricle with blue ink/gelatin, and various
      organs and tissues were removed from the body and fixed by immersion in 10%
      formalin. Sections 50-100 microm thick were incubated for ALPase in a medium
      containing naphthol AS-BI phosphate and fast red TR by the azocoupling method. In
      such specimens as the brain and skeletal muscles, ALPase activity was found in
      arterioles and capillaries on the arterial side, whereas it was absent in
      capillaries on the venous side and in venules. In the liver, only branches of the
      hepatic artery were positive. ALPase activity was absent in the vessels of the
      lung except for a positive reaction in branches of the bronchial arteries. These
      findings indicate that the ALPase activity is confined to the arterioles and
      arterial segments of the capillaries in the systemic circuit. Thus, ALPase
      staining of ink/gelatin injected specimens is a useful method for differentiating
      the arterial and venous segments of the micro-vascular bed in various organs and
      tissues in mice.

PMID- 9756100
TI  - MAP2 and GAP-43 expression in normal and weaver mouse cerebellum: correlative
      immunohistochemical and in situ hybridization studies.
AB  - MAP2 is a major microtubule-associated brain protein, selectively localized in
      dendrites; growth-associated phosphoprotein GAP-43 is a neuron-specific protein
      associated with axonal outgrowth. In adult cerebellum, both of these proteins and
      their corresponding RNA transcripts are most strongly expressed by granule cells.
      Using immunocytochemistry with antibodies and in situ hybridization
      histochemistry with [32P] labeled oligonucleotide probes, we examined the
      cellular localization of MAP2, GAP-43 and their mRNAs in the cerebellum of
      control and weaver (wv/wv) mutant mice, which exhibit massive granule cell death.
      In wild-type (+/+) mice, MAP2 immunoreactivity was seen in neuronal somata and
      dendrites of the granule cell layer; GAP-43 immunoreactivity was present in
      molecular layer, corresponding to the distribution of parallel fibres.
      Transcripts encoding MAP2 and GAP-43 were localized in the layer of the granule
      cell somata. In heterozygous weaver mice (wv/+), which feature an intermediate
      degree of granule cell loss, MAP2 immunoreactivity was localized in the granular
      layer, and the pattern of GAP-43 immunostaining was also similar to +/+, the only
      difference being a thinner molecular layer. Heterozygotes had an anatomical
      pattern of MAP2 and GAP-43 mRNA hybridization qualitatively similar to that of
      the wild-type with some deviations in signal intensity. In homozygous weaver
      mutants (wv/wv), MAP2 immunoreactivity was extremely weak in the area beneath
      Purkinje cells and a certain GAP-43 immunoreactivity was seen in the upper part
      of cerebellar cortex. Hybridization signals for MAP2 and GAP-43 mRNAs were
      minimal. The reported alterations in regional pattern of MAP2 and GAP-43
      expression in mutant mice offer a molecular correlate of dendritic and axonal
      protein gene transcription pertinent to the neuropathological manifestations of
      certain forms of heredodegenerative ataxia.

PMID- 9756101
TI  - Light and electron microscopic detection of anionic sites in the rat choroid
      plexus.
AB  - Electron microscopy of ultrathin sections stained with cationic iron colloid
      revealed that, in the choroid plexus of the rat brain ventricles, the luminal
      surface and fenestral diaphragm of the capillary endothelium as well as the
      basement membranes of the endothelium and epithelium are strongly anionic or
      intensely negatively charged. The iron colloid reaction to these anionic sites
      was erased by treatment with hyaluronidase or digestions with chondroitinase
      ABC/heparitinase/keratanase. These results indicate that sulfated proteoglycans
      provide such anionic sites of the choroidal capillaries. Discussion suggested
      that the negative charge on the luminal surface of the capillary endothelium
      prevents the adhesion of blood cells to capillary walls and also prevents
      endothelial adhesion by their repelling each other. It was further discussed that
      the negatively charged endothelial fenestrae and basement membranes may act as a
      charge barrier to inhibit the passage of anionic molecules.

PMID- 9756102
TI  - Electron microscopic characterization of filiform papillae in the normal human
      tongue.
AB  - The fine structure of filiform papillae on the normal human tongue was examined
      level by level, from the basal layer to the surface, in specimens taken from the
      dorsal side of the lingual body. Human lingual epithelia showed three distinct
      regions: epithelia on the anterior and on the posterior sides of filiform
      papillae and an interpapillary epithelium. While the basal and the squamous cell
      layers were similar throughout these three regions, differences were noted in the
      granular and the horny layers. The interpapillary epithelium actually lacked both
      the granular and the horny layers. The epithelium on the anterior side of
      filiform papillae was characterized by alternating layers of granular cells and
      of cornified cells. Granular cells possessed three types of keratohyaline-like
      granules within their cytoplasm: uniformly electron dense, relatively less
      electron dense, and a heterogeneous type. While the number of the keratohyaline
      like granules was remarkably diminished in the epithelium on the posterior side
      of filiform papillae, a considerable amount of tonofibrils was present in the
      cytoplasm. In the uppermost portion of the anterior side of filiform papillae,
      coherence between adjacent epithelial cells depended mainly on the interlocking
      of cytoplasmic villi and poorly developed desmosomes on villi. On the other hand,
      epithelial cells on the posterior side of filiform papillae appeared to be more
      tightly adhesive compared with those on the anterior side. This was due to focal
      thickening of the plasma membrane and to desmosomes at the interface between the
      granular and cornified cells, and to the formation of a marginal band and
      increased intercellular cement presumably derived from lamellar bodies in the
      horny layer. These findings demonstrate distinct differences between the anterior
      and the posterior sides of filiform papillae in the human tongue with respect to
      keratinization patterns, structures associated with cell-to-cell adhesion and the
      strength of cellular cohesion in the uppermost portion, and the turnover of
      cornified cells. These differences may contribute to the formation of the unique
      external configurations of filiform papillae.

PMID- 9756103
TI  - Acellular calcified columns in the normal growth plate of mouse vertebrae.
AB  - The present study aims to demonstrate the calcified columnar structures of the
      growth plate of mouse vertebrae and to show their age related changes. For light
      microscopy, paraffin sections of decalcified lumbar spines were stained with
      hematoxylin-eosin or toluidine blue; methacrylate sections of undecalcified
      specimens were stained to detect calcium precipitate. For scanning electron
      microscopy, lumbar spines treated with 5% NaClO solution were dehydrated by
      acetone and metal-coated. Light microscopy of hematoxylin-eosin stained sections
      revealed that the acellular columnar structures appeared between the chondrocyte
      stacks in the growth plate. These structures were stained more densely by
      toluidine blue. The methacrylate-embedded sections for calcium staining showed
      calcium deposition in the columns. Scanning electron microscopy of NaClO-treated
      specimens enabled the direct observation of the columns on both the epiphyseal
      and diaphyseal bone surfaces facing the cartilaginous growth plate. Numerous
      projections on each surface were distributed in mirror images ; the corresponding
      projections were similar in size and shape, indicating that the projections
      bonded with each other and formed calcified columns in the cartilaginous growth
      plate. Longitudinal sections of the spine confirmed these findings. The calcified
      columns first appeared about 2 or 3 weeks of age and increased in number with
      time. While increasing in number, they also grew in size fusing with the
      neighboring ones. The proportional area of the columns occupying the surface
      facing the growth plate also increased with age. These findings indicate that the
      calcified column ultimately concerns the cessation of the bone growth.

PMID- 9756104
TI  - Lymphatic drainage of the cerebrospinal fluid from monkey spinal meninges with
      special reference to the distribution of the epidural lymphatics.
AB  - The structural organization of the epidural lymphatics and lymphatic drainage of
      the cerebrospinal fluid from spinal meninges was studied in Japanese monkeys
      (Macaca fuscata) by an enzyme-histochemical method. The spinal meninges were
      examined at various intervals from 1 to 48 h, as well as at 30 days, following an
      injection of ultrafine carbon particles into the subarachnoidal space (cisterna
      magna). Lymphatics were differentiated from blood capillaries by the 5'
      nucleotidase (5'-Nase)-alkaline phosphatase (ALPase) double staining method (KATO
      et al. 1991, 1993) both in the whole-mount preparations and tissue sections.
      Carbon-filled collecting lymphatics and lymph nodes constantly appeared in the
      cervical and thoracic regions but only rarely in the lumbo-sacral region after
      carbon injection. Networks of 5'-Nase-positive lymphatics in the epidural
      connective tissues were seen in a large area on the dorsal surface around each
      spinal nerve root in the cervical and upper thoracic regions, especially at a
      level corresponding to the brachial plexus (C5-Th1). Carbon particles were often
      found within the 5'-Nase-positive lymphatics. In the lower thoracic and lumbo
      sacral regions, on the other hand, the epidural lymphatic network covered only a
      small area around each spinal nerve root. These findings suggest that the
      epidural lymphatics are well developed on the dorsal side of the lower cervical
      spinal dura mater and may function as an absorptive pathway for the cerebrospinal
      fluid from the subarachnoidal space.

PMID- 9756105
TI  - Non-pharmacological modification of cardiac risk factors: part 3. Smoking
      cessation and alcohol consumption.
AB  - Smoking cessation (SC) is probably the single most important risk factor
      modification for both primary and secondary prevention of cardiovascular disease.
      Interventions to stop smoking are highly cost effective. SC produces reductions
      in mortality and morbidity that generally outweigh any increase in risk due to
      weight gain, unless the gain is so great that it is accompanied by adverse
      changes in blood pressure, lipid profile or glucose tolerance. There is clear
      evidence that SC improves the lipid profile, decreases thrombotic tendency,
      reduces vascular endothelial damage and improves insulin sensitivity.
      Epidemiological studies consistently demonstrate a reduced risk of developing
      coronary heart disease (CHD) with moderate alcohol consumption (showing
      protection at < or = 2 drinks per day), but an increased risk at higher alcohol
      consumption levels. Potential mediators of these cardioprotective effects include
      an increase in high-density cholesterol (HDL-C), decreased clotting propensity,
      enhanced insulin sensitivity and glucose tolerance, and a possible lowering of
      blood pressure at low consumption levels in women. Alcohol consumption may not,
      however, compensate for the large increase in risk produced by smoking. Whereas
      moderate alcohol consumption slightly reduces the risk of death between the ages
      of 35 and 69 years, cigarette smoking approximately doubles the risk.

PMID- 9756106
TI  - Cefepime--assessment of its need at a tertiary care center.
AB  - OBJECTIVE: To assess the need and possible indications for a fourth-generation
      cephalosporin (cefepime). METHOD: A cohort study was carried out over a 17-month
      period in a 1500-bed Swiss university hospital. RESULTS: In 256 (22.6%) of the
      1135 patients followed consecutively by our Infectious Diseases Division,
      cefepime could have been chosen as an alternative to other broad-spectrum
      antibiotics, including imipenem/cilastatin (n=94), ciprofloxacine (n=52) and
      ceftazidime (n=49). Considering the low price-strategy of the pharmaceutical
      company promoting this drug in Switzerland, there would have been considerable
      cost savings for the hospital pharmacy if cefepime had been used as first-line
      treatment in these occasions. Nevertheless, we could not observe any potential
      advantage of cefepime compared to already introduced broad-spectrum antibiotics,
      except that cefepime was effective against infections caused by Enterobacter spp.
      resistant to ceftazidime. CONCLUSION: We conclude that fourth-generation
      cephalosporins such as cefepime may be introduced into large hospitals only after
      careful assessment of their potential benefits and that consultation by an
      Infectious Diseases Division is useful when evaluating the need for new broad
      spectrum antibiotics in the hospital setting.

PMID- 9756107
TI  - Placental transfer and neonatal effects of propofol in caesarean section.
AB  - OBJECTIVE: To assess transplacental passage of propofol by measuring the levels
      in maternal and foetal plasma, and the possible relationship between the latter
      and the neonatal effects when propofol is used as an induction agent in obstetric
      anaesthesia for performing a caesarean section to terminate pregnancy. METHODS:
      Intravenous propofol was administered as an anaesthesia-inducing agent at doses
      of 2 mg/kg in 10 healthy women (ASA I-II). The propofol concentrations were
      measured by high-performance liquid chromatography (HPLC). RESULTS: After
      induction, hypnosis was achieved in all patients within 75 s, and it took 4-10
      min to deliver the foetus. Apgar test scores were high in seven of the 10
      neonates, in three cases the score was 5 or less. The mean values in venous
      maternal blood were 5.01+/-1.06 microg/ml 1 min after propofol administration and
      1.47+/-0.35 microg/ml at the time of delivery. Propofol crossed the placental
      barrier with levels in the umbilical cord of 0.32+/-0.10 microg/ml in the vein
      and 0.22+/-0.08 microg/ml in the artery. CONCLUSION: Propofol plasma levels in
      the newborn at the time of delivery depend on the level in maternal plasma, and
      therefore on the dose used for induction and the time lapsed between the
      administration of the drug and the delivery of the foetus.

PMID- 9756108
TI  - Serum uric acid levels in cardiovascular diseases.
AB  - OBJECTIVE: Comparison of the serum uric acid levels of healthy people (n=71) and
      patients with cardiovascular diseases (CVD) (n=62). SUBJECTS AND METHODS: The
      patients included had either experienced acute myocardial infarction (AMI)
      (n=31), atherosclerosis (AT) (n=23) or ischaemia (n=8). The mean values (x+/-SD)
      of serum uric acid levels of the control group, the patients with CVD as a whole,
      and patients with AMI, AT and ischaemia were 4.15+/-0.45 mg%, 5.6+/-2.06 mg%,
      5.96+/-2.60 mg%, 5.38+/-1.22 mg% and 4.94+/-1.40 mg%, respectively. A
      statistically higher level of serum uric acid was found in the controls compared
      to the CVD patients (P < 0.05). CONCLUSION: The higher serum uric acid levels
      found in CVD patients suggests that any protective antioxidant effect which uric
      acid has is overwhelmed by other negative effects on pathogenesis.

PMID- 9756109
TI  - Valproic acid clearance in children with epilepsy.
AB  - OBJECTIVE: To evaluate population pharmacokinetics and the relationship between
      plasma concentration and daily dose of valproic acid (VPA) in a homogeneous group
      of children with epilepsy. METHODS: One hundred and fifty-one steady-state VPA
      plasma level measurements were made in 62 children aged 8 months to 6 years who
      were receiving VPA monotherapy. RESULTS: The level:dose ratio increased with age,
      its mean value was 1.7 in children aged under 2 years, 2.1 in children aged 2.4
      years and 3.3 in children aged 4.6 years. Weight-adjusted values of VPA clearance
      (Cl) decreased with increasing age. The Cl values in these three age groups were
      24.5+/-12.4 ml/kg/h, 19.9+/-6.1 ml/kg/h and 12.7+/-3.0 ml/kg/h, respectively. The
      relationship between VPA clearance and age was: Cl (ml/kg/h)=47.6 x age (months)(
      0.29), (r=-0.87). This equation allows the estimation of VPA plasma clearance on
      the basis of the child's age, within the range 8-72 months. Therefore, it can be
      used to establish the initial maintenance paediatric dose of VPA in monotherapy.
      CONCLUSION: The relationship between clearance and age should be useful when
      establishing a pharmacokinetic programme for VPA monotherapy in children.

PMID- 9756110
TI  - Whole saliva and plasma levels of clozapine and desmethylclozapine.
AB  - BACKGROUND: Therapeutic drug monitoring of clozapine as an aid in the treatment
      of schizophrenic states is commonly used in our hospital. OBJECTIVE: Development
      of a high-performance liquid chromatographic method for the determination of
      clozapine (CLZ) and its major metabolite desmethylclozapine (DMCLZ) in plasma and
      saliva, and investigation of the relationship between plasma concentrations of
      CLZ and DMCLZ and concentrations in saliva in patients treated with clozapine.
      METHODS: Subjects were either inpatients or outpatients with a DSM IV diagnosis
      of schizophrenia (n=34). Determination of CLZ and DMCLZ saliva concentrations
      appeared to be a satisfactory method to check compliance to treatment,
      particularly in outpatients. RESULTS: Mean CLZ and DMCLZ plasma concentrations
      were 432+/-264 ng/ml (+/-SD) (range 90-1310 ng/ml) and 257+/-144 ng/ml (range 55
      580 ng/ ml), respectively. The CLZ/DMCLZ plasma ratio was equal to 1.7+/-0-5
      (daily dosage 7.2+/-2.3 mg/kg, n=34). Mean CLZ plasma and saliva levels were
      336+/-157 ng/ ml (range 90-580 ng/ml) and 159+/-86 ng/ml (range 40-364ng/ml),
      respectively (r=0.56, n=14). Mean DMCLZ plasma and saliva levels were 196+/-112
      ng/ ml (range 55-481 ng/ml) and 109+/-67ng/ml (range 40-250ng/ml), respectively
      (r=0.73, n=14). Mean CLZ/DMCLZ ratios determined in plasma and saliva were 1.9+/
      0.6 (range 1.0-3.4) and 1.7+/-0.6 (range 1.0-3.2), respectively (r=0.85, n=14).
      CLZ and DMCLZ saliva concentrations appear to be useful for checking compliance
      to treatment, in particular among outpatients.

PMID- 9756111
TI  - Stability of cefazolin sodium eye drops.
AB  - OBJECTIVE: Assessing the stability of cefazolin sodium in preservative-free and
      preservative-containing eye drops. METHOD: Extemporaneous formulations of eye
      drops were prepared from a commercially-available parenteral product of cefazolin
      sodium: eye drops 'A' contained 50mg/ml of cefazolin sodium in 0.45% w/v sodium
      chloride solution, and eye drops 'B' contained 50 mg/ml, 0.005% w/v thiomersal
      and 1% w/v glycerol in water-for-injection. Cefazolin sodium concentrations in
      these eye drops were monitored by a stability-indicating HPLC assay method.
      Measurements of pH and osmolality, as well as tests for microbial contamination,
      were conducted. RESULTS: The eye drops stored at 4 degrees C were stable for 42
      days with minimal changes in pH and osmolality, but eye drops stored at room
      temperature were only stable for a few days with greater increments in pH and
      osmolality. None of the samples cultured had bacterial or fungal growth after 7
      days of incubation. CONCLUSION: Extemporaneously prepared formulations of
      cefazolin are unstable at room temperature and should be stored in a
      refrigerator.

PMID- 9756112
TI  - Evaluation of drug usage and expenditure in a hospital diabetes clinic.
AB  - BACKGROUND: Diabetes mellitus is a major public health problem and often coexists
      with hypertension and dyslipidaemia. A prescription-based survey was conducted to
      examine the use of antidiabetic, antihypertensive and lipid lowering drugs in a
      hospital diabetes clinic. The expenditure incurred was also evaluated. METHOD:
      Prescriptions issued from the diabetes clinic were collected for 4 consecutive
      weeks. Drugs were categorized into three main classes--antidiabetic,
      antihypertensive and lipid-lowering drugs. The unit cost of each drug and the
      total amount prescribed were used to estimate the total drug costs. RESULTS:
      During the 4-week study period, 534 prescriptions were collected, of which 520
      contained antidiabetic drugs. Oral hypoglycaemic agents were prescribed in 379
      patients (72.9%). Sulphonylurea was used as a single agent in 119 (22.9%)
      patients, in combination with metformin in 219 (42%) patients and with insulin in
      17 patients (3.3%). Among patients treated with sulphonylureas (n=342),
      glibenclamide (47.7%) and gliclazide (30.7%) were the main drugs prescribed.
      Metformin monotherapy was prescribed in only 31 patients (6%). Insulin treatment
      was prescribed in 141 (27%) patients and in combination with oral drugs in 23
      patients (4.5%). Of the 534 prescriptions, 225 (42%) contained antihypertensive
      drugs. Calcium channel blocking agents and angiotensin converting enzyme
      inhibitors were the most commonly prescribed drugs in both monotherapy (n=155)
      and combination therapy (n=70). The antidiabetic and antihypertensive drugs
      accounted for 45% and 39% of the total drug expenditure, respectively. Lipid
      lowering drugs were prescribed in 8% of the diabetic patients. Simvastatin and
      gemfibrozil were the most common drugs prescribed and accounted for 12% of the
      total drug expenditure. CONCLUSION: The use of antidiabetic drugs represents a
      major burden on the health care system. The high proportions of patients
      requiring antihypertensive drugs and lipid lowering drugs further increase drug
      expenditure. Most of these treatments have been shown to improve clinical
      outcomes and quality of life, if used appropriately. The impacts of these long
      term medications on health care financing require careful evaluation to assess
      their cost-effectiveness.

PMID- 9756113
TI  - Naproxen incorporated lipid emulsions. I. Formulation and stability studies.
AB  - BACKGROUND: Intravenous lipid emulsions stabilized with phospholipids have been
      an attractive alternative as vehicles for drug delivery, particularly for the
      parenteral administration of drugs with solubility problems. METHODS: Naproxen (a
      poorly aqueous soluble non-steroidal anti-inflammatory agent) emulsions were
      formulated with different types of emulsifiers (soybean lecithin, synperonic PEF
      127 and a 50:50 mixture of these). The stability of the various emulsion systems
      was evaluated at different temperatures (4, 25 and 40 degrees C) for a period of
      6 months by measuring changes in pH, droplet size, viscosity and percentage oil
      separation. The percentage of naproxen incorporation and the degree of haemolysis
      induced by the different types of emulsion systems was also determined. RESULTS:
      The emulsifier type showed a pronounced effect on the physicochemical properties
      of the emulsion systems, whereas storage temperature and time did not.
      Irrespective of emulsifier type, storage temperature and time, the percentage
      incorporation of naproxen in emulsions was between 80 and 100%. The degree of
      haemolysis induced by other emulsion components (dimethylsulfoxide (DMSO) and
      naproxen solution in DMSO) was about 10 times higher than that induced by
      emulsion systems. CONCLUSION: Choice of emulsifier is the most important factor
      in the stability of the naproxen emulsions.

PMID- 9756114
TI  - Compatibility and stability of fentanyl admixtures in polypropylene syringes.
AB  - OBJECTIVE: To determine the physicochemical stability of fentanyl in combination
      with midazolam and either hyoscine butylbromide or metoclopramide, and stored in
      30 ml polypropylene syringes. METHODS: Solutions containing approximately 40
      microg/ ml of fentanyl in combination with midazolam (approximately 600
      microg/ml) and either metoclopramide (approximately 700 microg/l) or hyoscine
      (approximately 850 microg/ml) were prepared from commercial ampoules of the
      drugs. The solutions were stored, in triplicate, in the dark at 32 degrees C (to
      simulate usage conditions) for 10 days, and the concentration of each constituent
      drug was periodically determined using a stability-indicating high-performance
      liquid chromatography assay. RESULTS: The combinations were relatively stable,
      with all drugs maintaining over 90% of their initial chemical potency for at
      least 1 week. There were no evident changes in either the physical appearance or
      pH values of the solutions over the course of the study. CONCLUSIONS: On the
      basis of physicochemical stability, polypropylene syringes containing fentanyl
      with midazolam and either hyoscine butylbromide or metoclopramide can be safely
      prepared and stored at or below 32 degrees C for periods of up to 1 week prior to
      use by palliative care patients receiving the drugs via a portable subcutaneous
      infusion device.

PMID- 9756115
TI  - Effective utilization of erythropoietin with intravenous iron therapy.
AB  - INTRODUCTION: Iron replacement therapy reduces the demand for erythropoietin
      (EPO) in some dialysis patients. It has been postulated that iron supply to the
      bone marrow is a rate-limiting step in the process of erythropoiesis under
      erythropoietin stimulation. METHODS: We evaluated the economic benefit of
      intravenous iron therapy for this purpose in a prospective, non-blinded study of
      22 haemodialysis patients, 16 male, six female, mean age 62 years (range 24-80
      years). All patients had a serum ferritin (SF) of < or = 60 microg/L, despite
      oral iron therapy. Patients with high aluminium and/or parathyroid hormone (PTH)
      levels, underlying bleeding/haematological disorders or active inflammatory
      diseases were excluded. Patients were established on subcutaneous EPO and given
      intravenous iron over seven consecutive dialysis sessions (total dose 1050 mg)
      and supplemental monthly doses with regular monitoring for 4 months. RESULTS: The
      median EPO dose was 4000 units/week (mean 6050 units/week) pre-treatment and 2000
      units/week (mean 3700 units) at 6 weeks post intravenous iron therapy (P=0.03).
      No serious adverse events occurred in the 154 treatment sessions of intravenous
      iron. Mean haemoglobin (Hb) level remained constant at 6 and 12 weeks (P=0.087).
      Serum ferritin levels (P< 0.0001) rose significantly, while a reduction in
      transferrin saturation (TS) became significant at the end of the study
      (P=0.0047). The use of intravenous iron allowed a substantial monthly cost saving
      per patient in our unit. CONCLUSION: Intravenous iron therapy is a safe and cost
      effective method for maintaining or improving Hb levels with a more effective
      utilization of EPO in patients with low SF levels despite oral iron therapy.

PMID- 9756116
TI  - Verapamil and acute dystonia.

PMID- 9756117
TI  - Iron stores in man in relation to diet and iron requirements.
AB  - OBJECTIVE: To calculate iron stores in man and their rates of changes in relation
      to iron requirements and dietary iron intake and bioavailability. METHOD: Newly
      established relationships between iron absorption from whole diets and serum
      ferritin (SF) and between SF and iron stores allow calculations of amounts of
      stored iron under different conditions (diets, losses) at stationary states when
      absorption equals losses. Rate of growth of stores can also be calculated. All
      calculations are based on observations and require no model assumptions. RESULTS:
      Present calculations of iron stores agree with previously observed phlebotomy
      values. Differences in intake and bioavailability of dietary iron and in iron
      requirements had marked effects on amounts of stored iron. A wide range of diets
      was studied, from a hypothetical high-meat diet typical for early man to diets in
      developing countries. A new equation is given for the translation of SF into iron
      stores. Analyses of growth rate of stores under different conditions showed a
      fast growth from zero iron stores during the first year (reaching about 80% of
      final amounts) followed by a much slower rate for 2-3 y. A marked inertia was
      seen in rate of changes in iron stores that was more marked the closer stores
      were to their stationary states making it difficult to use SF to estimate short
      term changes in iron absorption in iron replete subjects. CONCLUSIONS: Realistic
      Western-type diets with good bioavailability can cover iron requirements in most
      women and can restitute iron stores during lactation. The high prevalence of iron
      deficiency in menstruating Western women is thus mainly related to a further low
      bioavailability of iron in present diets. Present analyses also demonstrated an
      effective control of iron absorption preventing development of iron overload in
      otherwise healthy subjects even if the diet is fortified with iron and even if
      meat intake is high.

PMID- 9756118
TI  - Could antioxidants play a role in high rates of coronary heart disease in the
      Czech Republic?
AB  - OBJECTIVES: To compare plasma levels of antioxidant vitamins in the Czech
      population with those in a western European population, and to investigate
      whether plasma levels of antioxidant vitamins in Czech population are related to
      risk of MI. DESIGN: The study has two parts: a cross-sectional survey and a
      population based case-control study. SETTING: Adult population in two districts
      of the Czech Republic, and London based civil servants group as the comparison.
      SUBJECTS: A random sample of men and women aged 25-64y resident in two districts
      were selected for the cross- sectional survey. Subjects in the age group 40-49 y
      were compared to a sample of British civil servants of the same age enrolled in
      the Whitehall II Study. Men in the Czech sample served as controls to 52 male
      cases of first non-fatal myocardial infarction (MI) which occurred in the same
      population. Plasma samples were obtained from venepuncture during an interview in
      hospital in the population sample and immediately after hospitalization in the MI
      cases. MAIN OUTCOME MEASURES: Plasma levels of beta-carotene and alpha
      tocopherol, and the event of MI. Identical protocol and one laboratory was used
      for all analyses. RESULTS: The mean plasma levels of beta-carotene and alpha
      tocopherol in healthy Czech men and women were substantially lower than in a
      subsample of British civil servants examined in the same laboratory. Smoking was
      strongly related to beta-carotene in both populations but differences between
      Czechs and Brits were present in both smokers and non-smokers. In the case
      control study among Czech men, low levels of the vitamins were strongly related
      to an increases risk of MI. Age-adjusted odds ratios for concentrations below the
      median were 3.33 (95% confidence interval 1.43-8.33) for beta-carotene and 1.89
      (0.94-3.45) for alpha-tocopherol; further adjustment for a range of variables
      reduced these estimates only slightly. CONCLUSIONS: Plasma concentrations of
      antioxidants in the Czech population appeared to be very low, and men with low
      levels of these substances are at increased risk of MI. This indicates that sub
      optimal intake of antioxidants or related dietary factors may have played a role
      in the high rates of coronary heart disease in this population.

PMID- 9756119
TI  - A community based study of vitamin A and vitamin E status of adolescent girls
      living in the Shire Valley, Southern Malawi.
AB  - OBJECTIVE: To assess vitamin A and E status and anaemia in non-pregnant Malawian
      adolescent girls. DESIGN: A cross-sectional study in rural village communities in
      the Shire Valley, Southern Malawi. SUBJECTS: Adolescent girls, n = 118, aged
      between 10 and 19 y, 112 of whom were unmarried. METHODS: Socio-demographic
      information was collected by questionnaire, heights and weights were measured.
      Vitamin A was assessed by the Modified Relative Dose Response (MRDR) test, in
      addition to serum retinol values. Blood samples were collected 4-5 h after
      administration of 3,4-didehydroretinyl acetate. Retinol and alpha-tocopherol
      levels were measured by HPLC. Serum retinol results for non-pregnant girls were
      compared with values for 43 adolescent pregnant girls which were available from a
      previous study. RESULTS: 26.6% of non-pregnant girls had serum retinol values <
      0.70 micromol/L; 40.2% had an MRDR ratio > 0.060. In 59.3%, serum tocopherol
      levels were < 11.5 micromol/L and the tocopherol/cholesterol ratio was < 2.2 in
      23.9%. 11.3% had a haemoglobin > or = 12 g/dl. Vitamin A levels were
      significantly related to age, and younger girls were more likely to be deficient.
      Significant correlations were found between serum retinol, MRDR values and serum
      tocopherol. Girls with a low body mass index for age had tocopherol cholesterol
      ratios < 2.2. Low serum retinol values occurred significantly more often in
      stunted girls (P=0.01). Serum retinol values of adolescent pregnant girls were
      significantly lower than those of non-pregnant adolescents (P=0.002).
      CONCLUSIONS: Vitamin A and E deficiency and anaemia were common in adolescent non
      pregnant girls, and thought to partly result from increased growth requirements.
      Girls who become pregnant at an early age are at risk of depletion of their
      nutritional reserves. Measures to reduce nutritional deficiencies before the
      first pregnancy are needed.

PMID- 9756120
TI  - Anthropometric characteristics of older people in rural Malawi.
AB  - BACKGROUND: Older people are becoming an increasingly important proportion of the
      populations of developing countries, yet little information exists on their
      nutritional status or social conditions. OBJECTIVE: To assess the nutritional
      status of older people in rural Malawi. DESIGN: Cross-sectional study. SETTING:
      Lilongwe, Malawi. SUBJECTS: A total of 296 respondents (97 males and 199 females)
      aged from 55-94 y were studied. METHODS: Selected anthropometric measurements
      were taken by trained personnel. Among kyphotic respondents, height was estimated
      from armspan using regression equations derived from the non-kyphotic
      respondents. Body mass index (BMI) and corrected arm muscle area (CAMA) were
      computed using standard equations. RESULTS: The mean age of the respondents was
      63.3 y and 68.9 y among females and males, respectively. Kyphosis was seen in
      17.3% of all subjects and oedema in 4.1%. Nearly 90% of the subjects were
      involved in agricultural activities. Men were heavier and taller than women but
      women had larger MUACs and triceps skinfolds than males. The mean BMIs in kg/m2
      (+/- s.d.) were as follows: 19.7 (2.6) for men and 20.3 (3.0) for women. The
      prevalence of undernutrition, defined as BMI< 18.5 kg/m2, was 36.1% among males
      and 27.0% among females. In contrast, using MUAC (cut-offs 23 cm for males and 22
      cm for females), 20.4% of the men and only 10% of the women were classified as
      malnourished. CONCLUSION: The study demonstrated for the first time that
      undernutrition is a significant problem among older people in rural Malawi. It
      highlights the need to incorporate older people into existing and future
      nutrition and health programmes.

PMID- 9756121
TI  - Effects of dietary coconut oil, butter and safflower oil on plasma lipids,
      lipoproteins and lathosterol levels.
AB  - OBJECTIVE: The aim of this present study was to determine plasma levels of
      lathosterol, lipids, lipoproteins and apolipoproteins during diets rich in
      butter, coconut fat and safflower oil. DESIGN: The study consisted of sequential
      six week periods of diets rich in butter, coconut fat then safflower oil and
      measurements were made at baseline and at week 4 in each diet period. SUBJECTS:
      Forty-one healthy Pacific island polynesians living in New Zealand participated
      in the trial. INTERVENTIONS: Subjects were supplied with some foods rich in the
      test fats and were given detailed dietary advice which was reinforced regularly.
      RESULTS: Plasma lathosterol concentration (P < 0.001), the ratio plasma
      lathosterol/cholesterol (P=0.04), low density lipoprotein (LDL) cholesterol
      (P<0.001) and apoB (P<0.001) levels were significantly different among the diets
      and were significantly lower during coconut and safflower oil diets compared with
      butter diets. Plasma total cholesterol, HDL cholesterol and apoA-levels were also
      significantly (P< or =0.001) different among the diets and were not significantly
      different between buffer and coconut diets. CONCLUSIONS: These data suggest that
      cholesterol synthesis is lower during diets rich in coconut fat and safflower oil
      compared with diets rich in butter and might be associated with lower production
      rates of apoB-containing lipoproteins.

PMID- 9756122
TI  - Body composition changes in anorexia nervosa.
AB  - OBJECTIVE: To assess the body composition changes in anorexia nervosa and after
      medium term recovery. DESIGN: A descriptive study. SETTING: Rome, Italy.
      SUBJECTS: Twenty women affected by anorexia nervosa (AN) with a BMI [weight
      (kg)/height (m2)] below 17 kg/m2 and weight-stable for at least three months,
      were compared with 10 well nourished control women (CO) and nine rehabilitated
      subjects (R-AN), who had a BMI above 18.5 kg/m2 stable for at least the last six
      months. INTERVENTIONS: Body fat was assessed by underwater weighing, muscle mass
      by urinary creatinine, total body water (TBW) by impedance parameters (50 kHz and
      800 microA), skeletal mass by anthropometry and radius bone mineral density by
      dual photon absorptiometry in ultra-distal (UD-BMD) and medio-distal (MD-BMD)
      sites. RESULTS: The AN group, as compared to the control group, had a
      significantly lower weight, body mass index (BMI kg/m2) and percent body fat (P <
      0.0000). Creatinine urinary excretion was lowest in absolute term and when
      expressed as creatinine height index or per kg fat free mass (FFM) (P < 0.0000);
      muscle mass per kg body weight was 13% lower (P < 0.01). Ultra distal bone
      mineral density (UD-BMD) was 6% lower (not significant). TBW as percent of body
      weight was significant higher (P < 0.001): however TBW/FFM % was not
      statistically different with large inter-individual variability. An altered
      distribution of extra and intra-cellular water was suggested by the phase angle
      (AN: 4.4+/-0.8 degrees; CO: 6.1+/-0.4 degrees; (P < 0.0000). In rehabilitated
      anorexic patients (R-AN) the fat mass represented 53% of the weight gain. Their
      creatinine excretion remained still below the mean value of the controls (P <
      0.001). The impedance parameters were not significantly different between the R
      AN and the CO groups, however, the phase angle of the R-AN (5.0+/-0.7 degrees)
      remained lower than in the CO group, indicating that the water distribution was
      still altered. CONCLUSIONS: This study shows that AN is a condition of reduced
      body fat as well as of muscle mass, with a slightly reduced bone mass. In the
      course of rehabilitation, most of the weight regained is represented by fat,
      while the muscle mass appears to lag behind, at least in the medium term.

PMID- 9756123
TI  - Sources of bias in a dietary survey of children.
AB  - OBJECTIVE: To compare non-responders and responders to a dietary survey with
      respect to demographic variables and intention to choose selected breakfast
      foods, and to examine if there was any systematic change in number of food items
      reported during a 7 d recording period. DESIGN: Cross-sectional survey. SETTING:
      Molndal, Sweden. SUBJECTS: All pupils in 5th, 7th and 9th grades in the
      municipality were asked to complete a questionnaire during school hours. All
      those present (n = 1584, 92% of total) answered questions about lifestyle factors
      and about intentions, attitudes and beliefs concerning high-fibre bread and milk
      with varying fat content. All subjects in the initial sample were asked to fill
      in a 7 d record of food consumed. Acceptable food records were completed by 69%
      of the initial participants. RESULTS: Subjects not completing the food record
      differed significantly from participants with respect to demographic, lifestyle
      and dietary factors. Dropout was more common among those who reported not usually
      eating breakfast and among those intending to drink whole milk for breakfast. A
      decline in reported food items during the recording period was also observed.
      CONCLUSIONS: Two sources of bias were observed here, one indicating significant
      differences between non-participants and participants, the other suggesting the
      presence of a time-dependent trend in number of recorded foods. It is likely such
      biases are present in other dietary surveys involving schoolchildren, and should
      be taken into consideration in the design, analysis and interpretation of such
      studies.

PMID- 9756124
TI  - Fermented milk products are associated to ulcer disease. Results from a cross
      sectional population study.
AB  - BACKGROUND: Prevalence of peptic ulcer disease has been associated to diet. Some
      dietary factors seem to have bactericidal effect which may modify the risk of
      peptic ulcer disease. The objective was to analyze associations between dietary
      habits and peptic ulcers. DESIGN: A cross sectional population study. SUBJECTS:
      One thousand, one hundred and thirty-five subjects out of 11700 randomly invited
      men and women, aged 46-67 y, participating in a diet and disease study during
      1991-1993. The study population comprised of 764 cases with reported peptic
      ulcer, 142 with dyspeptic symptoms and 229 randomly selected controls. METHODS: X
      ray examinations and endoscopies were reviewed and 332 out of 764 peptic ulcer
      cases were verified. Mean daily intake of foods and nutrients were assessed with
      a combined 7d menu book and a quantitative food frequency questionnaire,
      including dietary supplements. RESULTS: Subjects with verified ulcer had lower
      intake of fermented milk products and vegetables and higher intake of milk, meat
      and bread than controls. Intake of total fat, saturated and monounsaturated fatty
      acids and linolenic acid were higher in the ulcer group. Higher intake of
      fermented milk products, by quintiles showed a decreased ulcer risk; odds ratio
      0.82 (0.71-40.95), adjusted for covariates below. Higher intake of milk, by
      quintiles, was associated with an increased risk of ulcer; odds ratio 1.17 (1.03
      1.32). Smoking, foreign ethnicity and being unmarried or divorced were covariates
      associated to ulcer. CONCLUSION: This study indicates the multifactorial etiology
      of peptic ulcer including dietary factors. High intake of fermented milk products
      was associated with decreased risk for ulcer, whereas increased risk was noted
      for high milk intake.

PMID- 9756125
TI  - Lipoprotein profiles and serum peroxide levels of aged women consuming palmolein
      or oleic acid-rich sunflower oil diets.
AB  - OBJECTIVE: To investigate the hypercholesterolemic effects of a dietary exchange
      between 16:0 and 18:1 while 18:2 was at relatively lower level (approximately 4%)
      in aged women with initially high total serum cholesterol (TC) and low density
      lipoprotein cholesterol (LDL-C) values and with high intakes of dietary
      cholesterol. DESIGN: Subjects were assigned to two consecutive 28 d periods. In
      the first period all subjects followed an oleic acid-rich diet in the form of
      oleic acid-rich sunflower oil. This was followed by a second period rich in
      palmitic acid in the form of palmolein. Nutrient intakes, serum lipids,
      lipoproteins, antioxidant vitamins, peroxides and LDL-peroxides were measured at
      two dietary periods. SETTING: Instituto de Nutricion y Bromatologia (CSIC),
      Departamento de Nutricion y Bromatologia I (Nutricion) and Seccion Departamental
      de Quimica Analitica, Universidad Complutense, Madrid, Spain. RESULTS: The
      palmolein period led to an increase in TC (P < 0.001; 17.7%) and serum
      apolipoprotein (Apo) B levels (P < 0.001; 18.0%). LDL-C and LDL-Apo B
      concentrations were higher (P < 0.001, 4.33+/-0.94 mmol/L and P < 0.01, 1.08+/
      0.20 g/L, respectively) following this period than following the oleic acid-rich
      sunflower oil diet (3.56+/-0.85 mmol/L, 0.93+/-0.16g/L, respectively). No
      significant differences were observed in the TC/high density lipoprotein
      cholesterol (TC/HDL-C) ratio between the two dietary periods. Serum and LDL
      peroxides were lower (P < 0.01, 49.5%, and P < 0.001, 69.0%, respectively) after
      the palmolein diet than after the oleic acid-rich sunflower oil diet. The
      palmolein diet significantly increased TC, LDL-C, Apo B, VLDL-ApoB, LDL-ApoB in
      women with TC > or = 6.21 mmol/L or with TC < 6.21 mmol/L, but the increase in
      Apo B, LDL-C and LDL-Apo B was greater among the women with high TC. The
      palmolein diet increased HDL-C in women with high or with low TC but this rise
      was on the borderline of statistical significance (P = 0.06) only in
      normocholesterolemics. Serum and LDL-peroxides tended to be higher in women with
      TC > 6.21 mmol/L than in women with TC < 6.21 mmol/L, but palmolein decreased
      serum and LDL-peroxide in hypercholesterolemics more than in the
      normocholesterolemics, resulting in serum and LDL-peroxide levels which
      theoretically are more adequate. CONCLUSIONS: Though palmolein increased LDL-C
      concentrations, it better protected LDL particles, mainly in women with high TC,
      against peroxidation than did oleic acid-rich sunflower oil.

PMID- 9756126
TI  - Plasma amino acids in anorexia nervosa.
AB  - OBJECTIVE: To evaluate the amino acid profile in a group of adolescents with
      anorexia nervosa, and to apply alternative ways of presenting and assessing
      results, so as to increase the information available for understanding the
      metabolic abnormalities developed in these patients. DESIGN: Plasma amino acid
      concentrations of a random group of patients with anorexia nervosa compared with
      values obtained from a 'healthy' adolescent population. SETTING: The study was
      performed at the tertiary children's Hospital Sant Joan de Deu. SUBJECTS: Female
      adolescents (n = 92, age: 15+/-1.8 y) at diagnosis of anorexia nervosa. Reference
      values for amino acids were obtained from apparently healthy adolescents (by
      history and analytical data) who underwent presurgical analysis for minor
      operations. INTERVENTIONS: Plasma amino acid concentrations were measured by ion
      exchange chromatography. Basic laboratory analysis, carnitine and IGF-I were also
      determined. RESULTS: In anorexic patients plasma concentrations of taurine,
      asparagine, glutamine, glycine, methionine, phenylalanine, ornithine, and
      histidine were significantly higher than reference values (Mann-Whitney, P < 0.01
      0.0001), whereas arginine and cystine were lower than our reference values (P <
      0.0001). Relative amino acid values (the molar fraction of the patient medians
      relative to control medians) were plotted. The ratios of some amino acids were
      significantly greater than those obtained from the reference population: Phe/Tyr
      (P < 0.001), Met/Cys (P < 0.0001), and Gly/Val (P < 0.01). CONCLUSIONS: A trend
      to hyperaminoacidemia is a common feature in anorexia nervosa. Although absolute
      amino acid values cannot play a significant role in the assessment of nutritional
      status in this condition, the calculation of some ratios (Phe/Tyr, Met/Cys and
      Gly/Val) and the graphical representation of relative values may be useful. The
      plasma amino acid profile in anorexia nervosa is different from those of other
      severe malnutrition states, showing a marasmic pattern of balanced protein-energy
      undernutrition. Cystine and arginine may be considered limiting amino acids in
      this disease, and the consequences of their deficient concentrations for
      oxidative damage should be further evaluated.

PMID- 9756127
TI  - Peripheral body fat has a protective role on bone mineral density in elderly
      women.
AB  - OBJECTIVES: To determine whether bone mineral density is lower in women living in
      homes for the elderly as compared to free dwelling control subjects, and to
      investigate factors affecting possible differences. This is the first study with
      this objective as the primary aim. DESIGN: Case-control study. SUBJECTS AND
      METHODS: Institutionalised independent elderly women (n = 22, mean age = 75.1 y+/
      6.43 s.d.) randomly selected in a home for the elderly and 22 age-matched control
      women randomly selected from a sample representative of the independent non
      institutionalised local population who underwent dual energy X-ray absorptiometry
      (DXA) at the lumbar spine and right femoral neck; anthropometric measurements
      (height, weight, subscapular and triceps skinfold thickness); general
      questionnaire. RESULTS: Mean bone mineral density at the femoral neck was 0.618
      g/cm2 (+/-0.130s.d.) in institutionalised women and 0.709 g/cm2 (+/-0.106 s.d.)
      in controls (P = 0.02, t-test). Controlling for confounding factors in the
      analysis of covariance, triceps skinfold thickness and living in a home for the
      elderly turned out to be significant determinants of bone mineral density.
      CONCLUSION: When compared to free dwelling control subjects, institutionalised
      women show lower bone density, that is the main risk factor for fracture. Reduced
      peripheral body fat was significantly associated with the low bone mineral
      density observed. Health programs aimed at decreasing the incidence of fractures
      among institutionalised subjects will also have to consider the effect of
      nutritional or life style factors that reduce peripheral body fat.

PMID- 9756128
TI  - Paper by Doucet, Almeras, White, Despres, Bouchard and Tremblay: Dietary fat
      composition and human adiposity, Eur J Clin Nutr (1998); 52: 2-6.

PMID- 9756130
TI  - IL-6 functions in cynomolgus monkeys blocked by a humanized antibody to human IL
      6 receptor.
AB  - A humanized antibody to the human interleukin-6 receptor (IL-6R), hPM-1, blocked
      the interleukin-6 (IL-6) functions in normal cynomolgus monkey lymphocytes in
      vitro. The binding activity of hPM-1 to non-human primate IL-6R was examined in
      peripheral blood lymphocytes by flow cytometry. PM-1 recognized the IL-6R on T
      lymphocytes of cynomolgus and rhesus monkeys, but did not on those of marmosets.
      The homology between human IL-6R and its cynomolgus monkey counterpart was 97.3%
      in the extracellular domain of the amino acid sequence, as determined by DNA
      sequencing of the PCR product from peripheral blood mononuclear cells. PM-1
      inhibited two functional parameters in vitro in cynomolgus monkeys: (1), T-cell
      proliferation stimulated by phytohemaglutinin and human IL-6; (2), Immunoglobulin
      G-production evoked by Staphylococcus aureus Cowan-1- and human IL-6-stimulated B
      lymphocytes. These data show that hPM-1 binds to and functionally blocks the
      cynomolgus monkey IL-6 receptors.

PMID- 9756129
TI  - Erratic behavior of nitric oxide within the immune system: illustrative review of
      conflicting data and their immunopharmacological aspects.
AB  - The literature data assembled in this article document the variation of
      immunobiological effects of nitric oxide (NO). A number of factors are obviously
      responsible for the diversity, ranging from inactivity, alleviation, but not
      rarely to exacerbation of certain pathogenetic processes. A better understanding
      of NO interactions with the immune system can only be reached if more complex
      experimental designs to study the effects of reactive nitrogen species are
      adopted in the future. They should integrate major participating variables and
      take into account pharmacodynamic/kinetic aspects of NO production in triggering
      the ultimate effects. If manipulation of NO in the organism by means of recently
      developed NO inhibitors and NO donors is to become a rational tool of
      immunopharmacological strategies, detailed knowledge of their pharmacologies and
      toxicologies is urgently needed in order to differentiate between the effects of
      NO and other side effects. Hopefully, this approach could improve the
      predictability of the clinical outcomes of NO manipulation.

PMID- 9756131
TI  - Stimulation of macrophages by Bacillus firmus: production of nitric oxide and
      cytokines.
AB  - Immunostimulatory properties of gram-positive Bacillus firmus were investigated
      under in vitro conditions using murine peritoneal macrophages. B. firmus
      stimulated in a concentration and time dependent manner the secretion of tumour
      necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10), but it had no
      influence upon interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) production.
      It also substantially augmented production of nitric oxide (NO) induced by
      exogenous IFN-gamma. Inhibitory experiments using neutralizing antibodies against
      TNF-alpha and/or IL-10 have demonstrated that these cytokines are responsible for
      triggering the underlying mechanism(s) leading to enhanced NO production. The
      cytokine-stimulatory and NO-costimulatory properties could participate in the
      antiinfectious and anticancer effects of B. firmus, detected previously in the in
      vivo experiments.

PMID- 9756132
TI  - The pharmacokinetics and metabolism of 14C/13C-labeled ortho-phenylphenol
      formation following dermal application to human volunteers.
AB  - 1. The pharmacokinetics and metabolism of uniformly labeled 14C/13C-ortho
      phenylphenol (OPP) were followed in six human male volunteers given a single 8 h
      dermal dose of 6 microg OPP/kg body weight formulated as a 0.4% (w/v) solution in
      isopropyl alcohol. The application site was covered with a non-occlusive dome
      allowing free movement of air, but preventing the loss of radioactivity due to
      physical contact. At 8 h post-exposure the non-occlusive dome was removed, the
      dose site was wiped with isopropyl alcohol containing swabs and the skin surface
      repeatedly stripped with tape. Blood specimens, urine, and feces were collected
      from each volunteer over a 5 day post-exposure period and were analyzed for
      radioactivity and metabolites (urine only). 2. Following dermal application, peak
      plasma levels of radioactivity were obtained within 4 h post-exposure and rapidly
      declined with virtually all of the absorbed dose rapidly excreted into the urine
      within 24 h post-exposure. A one-compartment pharmacokinetic model was used to
      describe the time-course of OPP absorption and clearance in male human
      volunteers. Approximately 43% of the dermally applied dose was absorbed through
      the skin with an average absorption half-life of 10 h. Once absorbed the renal
      clearance of OPP was rapid with an average half-life of 0.8 h. The rate limiting
      step for renal clearance was the relatively slower rate of dermal absorption;
      therefore the pharmacokinetics of OPP in humans was described by a 'flip-flop'
      single compartment model. Overall, the pharmacokinetics were similar between
      individuals, and the model parameters were in excellent agreement with the
      experimental data. 3. Approximately 73% of the total urinary radioactivity was
      accounted for as free OPP, OPP-sulfate and OPP-glucuronide conjugates. The
      sulfate conjugate was the major metabolite (approximately 69%). Therefore, total
      urinary OPP equivalents (acid-labile conjugates+free OPP) can be used to estimate
      the systemically absorbed dose of OPP. 4. The rapid excretion of OPP and
      metabolites into the urine following dermal exposure indicates that OPP is
      unlikely to accumulate in humans upon repeated exposure. Based on these data,
      blood and/or urinary OPP concentration (acid-labile conjugates) could be utilized
      to quantify the amount of OPP absorbed by humans under actual use conditions.

PMID- 9756133
TI  - Medicinal herb, Thonningia sanguinea protects against aflatoxin B1 acute
      hepatotoxicity in Fischer 344 rats.
AB  - 1. Thonningia sanguinea, a plant used prophylactically against bronchial asthma
      in Ghana was recently found to have antioxidative and hepatoprotective actions in
      our laboratory. 2. In this study, the effect of T. sanguinea extract on certain
      biochemical indices in serum and liver of Fischer 344 rats given a single
      intraperitoneal (i.p.) dose (1 mg/kg) of aflatoxin B1 (AFB1) was investigated. 3.
      Administration of AFB1 resulted in significant increases in serum alanine
      aminotransferase (ALT) and glutathione S-transferase (GST) levels and a
      significant decrease in aniline hydroxylase activity in liver microsomes. When T.
      sanguinea (5 ml/kg) was intraperitoneally administered to rats 12 h and 1 h
      before AFB1, liver injury was significantly reduced as seen in the decreased
      levels of serum ALT and serum GST. However, the decrease in aniline hydroxylase
      activity by AFB1 was not recovered but enhanced by T. sanguinea pre-treatment. 4.
      Kinetic analysis of cytochrome P450 activity of rat liver microsomes in vitro
      demonstrated that T. sanguinea inhibited aniline hydroxylase non-competitively
      suggesting depression of biotransformation of AFB1 to toxic metabolites. 5. The
      data indicate a hepatoprotective action of T. sanguinea against AFB1-induced
      liver injury.

PMID- 9756135
TI  - Implications of the hormesis hypothesis for risk perception and communication.

PMID- 9756134
TI  - Effect of single neonatal vitamin D3 treatment (hormonal imprinting) on the bone
      mineralization of adult non-treated and dexamethasone treated rats.
AB  - Hormonal imprinting (the first encounter between the hormone and receptor after
      birth) is needed for the normal development of receptor. Presence of the
      appropriate hormone in excess, or its absence, as well as presence of hormone
      like molecules able to bind to the maturing receptor in this time, can cause
      faulty imprinting. In this experiment the effect of neonatal treatment with a
      single dose of 0.05 mg cholecalciferol (vitamin D3) was studied by bone
      densitometry. The treatment caused significant decrease of body weight in 3-month
      old females and also significant reduction of bone mineral density (BMD) and bone
      mineral content (BMC) in males. Dexamethasone treatment of 3-month old rats for
      10 days increased BMD in males and BMC in females without affecting body weight.
      The double treatment (vitamin D neonatally and dexamethasone when adult)
      decreased the body weight of both sexes and increased BMD in males, and BMC,
      BMD/bw and BMC/bw in both sexes, related to the control or the only vitamin D
      treated groups. Considering the hormonal imprinting effect of neonatal vitamin D
      treatment at glucocorticoid receptorial level in other experiments, similar
      effects also can be supposed for vitamin D itself, manifested in the changes of
      bone mineralization.

PMID- 9756136
TI  - If hormesis exists...: implications for risk perception and communication.

PMID- 9756137
TI  - Regulatory implications of hormesis.

PMID- 9756138
TI  - Hormesis as a default parameter in RfD derivation.

PMID- 9756139
TI  - Molecular analyses of adaptive survival responses (ASRs): role of ASRs in
      radiotherapy.
AB  - Adaptive survival responses (ASRs), whereby cells demonstrate a survival
      advantage when exposed to very low doses of ionizing radiation (IR) 4 - 24 h
      prior to a high dose challenge, were first reported over 15 years ago. These
      responses were linked to hormesis, which implied that exposure to low levels of
      IR may be beneficial to the cell. We postulate that increased survival does not
      necessarily mean that the treatment is beneficial. Studies at the molecular level
      indicate that ASRs are the result of misregulated cell cycle checkpoint
      responses, occurring in the G1 phase of the cell cycle after IR. Specific gene
      products (i.e., PCNA, cyclin D1, cyclin A, XIP8, xip5 and xip13) appear to
      control these cell cycle checkpoint responses. Certain neoplastic cells show
      potent ASRs because they bypass checkpoints which would otherwise lead to
      apoptosis or other forms of cell death (possibly necrosis), and/or these cancer
      cells lack genetic factors, such as specific caspases (cysteine aspartate
      specific proteases), that control apoptosis. Alterations in these cell cycle
      checkpoints or apoptotic responses may also occur during IR-induced stress
      responses in normal cells, at critical times (10-18 days posttreatment) following
      IR. One IR-induced protein, XIP8, may be a critical controlling factor at this
      point where delayed-onset apoptosis occurs. Additionally, we have shown that the
      presence or absence (i.e., SCID cells) of nonhomologous DNA double strand break
      repair did not seem to influence ASRs, suggesting that ASRs may be caused by
      signal transduction stress responses. ASRs may be beneficial to survival,
      however, the consequence(s) of that survival may be dire. For example, many
      neoplastic cells exhibited far greater ASRs than normal cells. Additionally, ASRs
      were induced by as little as 1 cGy and and were enhanced by repeated exposures of
      low level radiation. The implications for radiotherapy are that when a patient
      arrives for port film imaging during the course of therapy, the dose-rate,
      overall level of exposure, and time between port film exposure and high dose IR
      treatment become potentially important factors for improved efficacy of treatment
      of certain cancers. Further research is warranted to determine what molecular
      factors are most important for ASRs, and current work is focusing on XIP8.

PMID- 9756140
TI  - Hormesis--implications for risk assessment caloric intake (body weight) as an
      exemplar.
AB  - Hormesis can be considered as a parameter which has a non-monotonic relationship
      with some endpoint. Since caloric intake is such a parameter, and the impact of
      this parameter on risk assessment has been fairly well characterized, it can
      provide clues as to how to integrate the information from a hormetic parameter
      into risk assessments for toxicants. Based on the work with caloric intake, one
      could: (a) define a biomarker for hormetic effect; (b) integrate specific
      information on when in the animals lifespan the parameter is active to influence
      parameters such as survival; (c) evaluate component effects of the overall
      hormetic response; and (d) address the consequences of a non-monotonic
      relationship between the hormetic parameter and endpoints critical for risk
      assessment. These impacts on risk assessments have been characterized for chronic
      tests, but are also true for short-term tests. A priority is the characterization
      of the dose-response curves for hormetic parameters. This quantification will be
      critical in utilizing them in risk assessment. With this information, one could
      better quantitatively address the changes one expects to result from the hormetic
      parameter, and limit the uncertainty and variability which occurs in toxicity
      testing.

PMID- 9756141
TI  - Risk assessment and risk management implications of hormesis.

PMID- 9756142
TI  - Risk management for plausibly hormetic environmental carcinogens: the case of
      radon.
AB  - Risk management typically involves efforts to reduce human exposures by
      establishing regulations that limit the concentration of the substance in
      environmental media. In cases where a substance is widely used in commerce or is
      naturally occurring in the environment, compliance costs can be substantial
      because of nationwide requirements to add expensive control technologies.
      Uncertainties in a dose-response function further impact risk management
      decisions because they may correspond to large differences in health benefit per
      unit exposure reduction. These problems are highlighted in the case of plausibly
      hormetic environmental carcinogens, for which a linear-no-threshold (LNT) dose
      response model has been the traditional regulatory default assumption. In this
      case, model uncertainty is pivotal, and risk management is consequently
      inherently controversial. However, marginal cost functions that arise for
      plausibly hormetic carcinogens are expected to possess a common analytic feature
      that may be particularly useful for this type of risk management problem.
      Specifically, marginal cost functions in this context are expected to have roots
      reflecting contaminant concentration values above which regulatory goals may be
      optimally placed subject to cost constraints. Here we illustrate this heuristic
      feature in the case of residential radon, using both a LNT model and a
      biologically plausible hormetic model to predict associated risks of lung cancer
      mortality.

PMID- 9756143
TI  - Parkinson's disease: neurodegenerative mechanisms and neuroprotective
      interventions--report of a workshop.

PMID- 9756144
TI  - N-0923, a novel soluble dopamine D2 agonist in the treatment of parkinsonism.
AB  - N-0923, a novel aminotetralin dopamine D2 agonist, was shown to effectively
      reverse parkinsonian symptoms in nine dopa/agonist-responsive Parkinson's disease
      patients. The drug was given up to 4.5 hours by continuous intravenous (i.v.)
      infusion using an i.v. pump. The onset of anti-parkinsonian effect was seen
      within minutes of the initiation of the infusion and was absent within 90 minutes
      of cessation of the infusion. The short elimination half-life of N-0923 (90 min)
      would allow for the rapid initiation of drug effect when necessary and at the
      same time permit the effect to be terminated quickly if necessary. The drug would
      be useful in situations where oral medication is not feasible or is associated
      with erratic absorption. The patients tolerated the drug well. Dose escalation
      load was limited by nausea and vomiting. It should be noted that the doses were
      increased until these symptoms occurred, but therapeutic effects were noted well
      before the side effects occurred. Using a modified Columbia scale, maximum
      improvement consisted of a 27-95% drop in score. Maximum response was obtained at
      infusion rates varying from 2-16 microg/kg per hour and at blood levels of 0.11
      1.49 microg/mL.

PMID- 9756145
TI  - Pallidotomy improves motor responses and widens the levodopa therapeutic window
      in Parkinson's disease.
AB  - Stereotactic posteroventral pallidotomy (PVP) as a treatment for Parkinson's
      disease (PD) symptoms has been increasingly used in moderate-advanced disease. We
      examined the pharmacodynamic responses of PD patients to single oral levodopa
      doses and intravenous levodopa infusions before and after PVP surgery. Nine
      subjects with advanced PD received a single oral dose and ramped intravenous
      levodopa infusions before and 3-5 weeks after unilateral PVP. Timed motor tasks,
      Unified Parkinson's Disease Rating Scale (UPDRS) evaluations, and ordinal
      dyskinesia rating were performed after oral levodopa and during i.v. levodopa
      infusions. Serum prolactin and dopa levels were measured during the levodopa
      infusions. Overall timed motor but not motor UPDRS scores were improved after PVP
      in both the worst ("off") and best ("on") states. Contralateral but not
      ipsilateral limb dyskinesias were substantially reduced at all serum (dopa)
      levels after PVP. Ipsilateral and contralateral timed motor performance at low
      serum (dopa) levels was improved by PVP. Walking speeds at all serum (dopa)
      levels were not changed by PVP. Serum prolactin was reduced equally by increasing
      (dopa) preoperatively and postoperatively. PVP significantly and favorably
      altered oral and intravenous levodopa pharmacodynamics by improving bilateral
      limb motor function and contralateral dyskinesia but did not alter walking speed.
      PVP appears to widen significantly the therapeutic window for levodopa in PD.

PMID- 9756146
TI  - A double-blind, placebo-controlled study of intranasal apomorphine spray as a
      rescue agent for off-states in Parkinson's disease.
AB  - Nine patients with advanced levodopa-responsive Parkinson's disease were enrolled
      in a double-blind, placebo-controlled crossover trial of intranasal apomorphine
      as rescue therapy for parkinsonian off-states. Patients were assigned in random
      order to each of four possible combinations of apomorphine, trimethobenzamide
      antiemetic, and their matched placebos and received detailed in-office motor
      scoring during each of the four study periods. Patients also completed diaries
      describing the effectiveness of the nasal spray for reversing off-states. A
      statistically significant reduction in the Unified Parkinson's Disease Rating
      Scale (UPDRS) motor score was seen following active apomorphine during in-office
      evaluation visits but not following placebo nasal spray. Patient diaries revealed
      that active apomorphine had a latency to onset of 11 minutes and a duration of 50
      minutes. Significant nausea from apomorphine spray was seen in only one patient
      whereas nasal irritation was disabling in three and mild in two. We conclude that
      intranasal apomorphine is an effective rescue agent for parkinsonian off-states
      although nasal irritation is a limiting factor.

PMID- 9756147
TI  - Dopamine D3 receptor is decreased and D2 receptor is elevated in the striatum of
      Parkinson's disease.
AB  - The mesolimbic dopamine (DA) system preferentially innervates the D3 receptor,
      whereas the D2 receptor is, in addition, a target of the nigrostriatal DA system.
      In human brain D3 receptors and D3 mRNA-expressing neurons are largely segregated
      to brain regions that are the targets of the mesolimbic DA system and the
      efferents of the "limbic striatum." Thus, D3 receptors may regulate effects of DA
      on the "limbic" cortico-striatal-pallidal-thalamic-cortical loop. The
      nigrostriatal DA system is considerably more damaged in Parkinson's disease (PD)
      than the mesolimbic DA system. We report here, using radioligands selective for
      the D2 and D3 receptor, that these receptors are independently changed in PD.
      Tissue collected at autopsy from nine subjects with a diagnosis of PD and eight
      age-matched subjects with no evidence of a neurologic disorder was processed for
      [125I]epidepride binding to D2 receptors, [125I] trans-7-OH-PIPAT binding to D3
      receptors, [125I]RTI-55 for the DA transporter (DAT), and immunoautoradiography
      for tyrosine hydroxylase (TH) using autoradiographic methods. Dopaminergic
      innervation to the caudal putamen was profoundly reduced and to a lesser extent
      in the rostral putamen in PD. DAT sites but not TH protein levels were reduced in
      the nucleus accumbens (NAS) in PD compared with age-matched control subjects.
      This is consistent with a loss of dopaminergic innervation from the mesolimbic DA
      system but elevation in TH production. D3 receptors were significantly reduced in
      PD by 40-45% particularly in the NAS and putamen. D2 receptors were elevated in
      PD in the dorsal putamen by 15%. The reduction in D3 receptor number was not
      observed in PD cases with a diagnosis of less than 10 years. The changes in DA D3
      receptor number is interesting in light of the development of antiparkinsonian
      agents that are D3-preferring agonists.

PMID- 9756148
TI  - Amantadine reduces levodopa-induced dyskinesias in parkinsonian monkeys.
AB  - The antidyskinetic potential of the glutamate NMDA receptor channel blocker
      amantadine was evaluated in four levodopa-primed parkinsonian monkeys using two
      different regimens (1.25 or 2.5 mg/kg administered subcutaneously twice daily for
      3-6 days). When administered with a relatively low dose of levodopa, amantadine
      produced a near-total suppression of choreiform dyskinesias and a substantial
      reduction in dystonic dyskinesias at the expense of a significant reduction in
      antiparkinsonian response. With a high dose of levodopa, amantadine had a smaller
      but still significant effect on dyskinesias without altering the antiparkinsonian
      response. These results lend support to the view that glutamate receptor-mediated
      mechanisms contribute to levodopa-induced dyskinesias. They also suggest that
      amantadine could alleviate such complications in parkinsonian patients,
      especially with careful dose optimization.

PMID- 9756149
TI  - Clinical characteristics of essential tremor: data from a community-based study.
AB  - BACKGROUND: 99.5% of individuals with essential tremor (ET) who live in the
      community have mild tremor and do not attend clinics. Clinic-based studies of ET
      have not allowed investigators to characterize the full clinical spectrum of this
      disorder. In community-based studies of ET, the primary focus has been the
      prevalence rather than the clinical characteristics of ET. OBJECTIVE: To describe
      the clinical characteristics of ET as seen in a community-based study. METHODS:
      73 subjects with ET, identified in a community-based study of ET in Washington
      Heights-Inwood, New York, underwent a standardized 84-item physician-administered
      tremor interview and a 26-item videotaped tremor examination which included 12
      bedside tests for ET. Two neurologists who specialized in movement disorders and
      who demonstrated excellent interrater agreement rated the severity of tremor
      using a 0 to +3 clinical rating scale and assigned a total tremor score (range, 0
      36) and a diagnosis of ET. RESULTS: Diagnoses in the 73 cases were: definite ET
      (18, 24.7%), probable ET (32, 43.8%), and possible ET (23, 31.5%). The mean total
      tremor score was 17.8 of 36. Thirty-six of 73 (49.3%) were asymptomatic,
      answering "no" to the question "do you often have shaking or tremor that you
      can't control?" Sixty-seven of 73 (91.8%) had not been prescribed medication for
      tremor. On average, subjects received tremor ratings of > or =+2 on only 5.4 of
      the 12 bedside tests for ET. Kinetic tremor was rated as more severe than
      postural tremor in 72 (98.6%) of 73 cases. CONCLUSIONS: We present the clinical
      findings of a group of largely untreated, unselected cases of ET that would not
      otherwise have come to neurologic attention. The tremor was mild, often
      asymptomatic, and not uniformly present throughout the examination. It was rarely
      treated. The kinetic component of the tremor was more severe than the postural
      component. These clinical data further our understanding of the clinical spectrum
      of ET.

PMID- 9756150
TI  - Sternomastoid function during hemispheric suppression by amytal: insights into
      the inputs to the spinal accessory nerve nucleus.
AB  - The debate as to whether the sternomastoids receive ipsilateral, contralateral,
      or bilateral cortical innervation is based largely on the observation of stroke
      patients and, to a lesser extent, on animal experimentation. The variability of
      vascular lesions, the lack of pathology correlation in the early reports, and the
      differences in posture between humans and laboratory animals contributed to the
      controversy. We studied the function of the sternomastoid (SM) muscles during
      transient, complete left hemiplegia in 18 right-handed patients undergoing a Wada
      test. After injection in the right internal carotid artery (ICA), 14 patients
      were able to lift and turn their heads both to the right and to the left on
      command. Ten of the 14 patients who were able to follow commands after the
      injection had weakness of the right sternomastoid compared with the left. Our
      findings demonstrate that the left hemisphere can activate both the right and the
      left sternomastoid muscles during suppression of the right hemisphere. The
      sternomastoids receive bilateral hemispheric innervation and the maximal input
      comes from the ipsilateral hemisphere.

PMID- 9756151
TI  - Brain phospholipids and fatty acids in Friedreich's ataxia and spinocerebellar
      atrophy type-1.
AB  - Previous studies of patients with spinocerebellar atrophy type 1 (SCA-1) and
      Friedreich's ataxia (FA) have suggested the occurrence of membrane disturbances
      in both disorders. We measured concentrations of phosphatidylcholine (PC), diacyl
      and plasmalogen phosphatidylethanolamine (PE), and phosphatidylserine (PS), along
      with their fatty acid profiles, in the brains of eight patients with Friedreich's
      ataxia (FA) and nine patients with dominantly inherited spinocerebellar atrophy
      type 1 (SCA-1). Compared with the controls, levels of all phospholipid types (PE,
      PS, and PC) were reduced in the cerebellar but not occipital cortex of SCA-1
      patients. In contrast, in the FA group, levels of PS and PE, but not PC, were
      reduced in both cerebellar and occipital cortices. The fatty acid composition of
      individual brain phospholipids was altered in both FA and SCA-1 patients, most
      markedly in the plasmalogen PE and PS classes of cerebellar phospholipids. Given
      the neuropathologic characteristics of each disorder, it is likely that altered
      fatty acid composition and phospholipid levels in SCA-1 cerebellar cortex occur
      as a consequence of pronounced cerebellar degeneration. In contrast, reduced
      phospholipid levels in FA cerebellar and occipital cortex, areas characterized
      by, at most, minimal neuronal loss in FA, may represent a widespread alteration
      in cellular phospholipid metabolism occurring in response to the specific gene
      defect in the disorder.

PMID- 9756152
TI  - Polysomnographic sleep measures in patients with uremic and idiopathic restless
      legs syndrome.
AB  - In the present study, the nocturnal electroencephalographic sleep pattern, the
      number of periodic leg movements (PLM) during sleep and wakefulness, and the
      subjective sleep parameters of patients with uremic (n = 10) and idiopathic (n =
      17) restless legs syndrome (RLS) were compared. The main finding was that the
      total number of PLM (p = 0.019), the PLM index (p = 0.018), and the PLM index
      while awake (p = 0.003) were significantly higher in patients with uremic RLS
      compared with patients who had idiopathic RLS. Additionally, both groups showed a
      distinct time-of-night pattern of PLM activity. Polysomnographic measures of
      sleep continuity (total sleep time, sleep efficiency, sleep onset latency, time
      awake) and sleep architecture (amount of nonrapid eye movement sleep stages 1, 2,
      3, and 4 and the amount of rapid eye movement sleep) did not differ between
      uremic and idiopathic RLS patients. With regard to subjective parameters, sleep
      quality was estimated to be worse in uremic RLS (p = 0.033), whereas other
      parameters (for example, severity of RLS, quality of life) did not differ between
      the two groups. It is suggested that uremia itself worsens the motor symptoms of
      RLS, probably as a result of increased excitability.

PMID- 9756153
TI  - Adult head-banging and stereotypic movement disorders.
AB  - Stereotypic movement disorders (SMD) such as head-banging, which are common among
      children with mental retardation or pervasive developmental disorders, may also
      occur in intellectually normal adults. We report a 27-year history of daily head
      banging with self-injury in a 49-year-old man with normal cognition. The patient
      had no personal or family history of Tourette's syndrome, tic disorder, obsessive
      compulsive disorder (OCD), or mental retardation. The frequency of his
      stereotypical head-banging increased with anxiety, loud noises with startle, and
      boredom. He reported a sense of pleasure from his head-banging, and the frequency
      of this behavior decreased when he was treated with the opioid antagonist
      naltrexone. Although not diagnostic, the self-stimulatory or pleasurable
      component of head-banging, body-rocking, thumb-sucking, and other SMD may help
      distinguish them from tics, Tourette's syndrome, OCD, and deliberate self-harming
      behavior. This report reviews the disorders associated with SMD and discusses the
      potential mechanisms for these behaviors. The treatment of SMD includes drugs
      that work through opioid, serotonergic, or dopaminergic systems.

PMID- 9756154
TI  - Effective treatment of orthostatic tremor with gabapentin.
AB  - We report seven patients with orthostatic tremor (OT) who were successfully
      treated with the anticonvulsant gabapentin. Five of the patients had been
      previously tried on clonazepam, the most commonly used drug for OT, four without
      any benefit. The degree of improvement perceived by the patients with gabapentin
      varied from 60-80% (mean 73%). The effective dose of gabapentin ranged from 300
      1800 mg/day (mean 1030 mg/day). The side effects were generally mild, transient,
      and dose-related. Duration of response has so far ranged from 2-22 months (mean
      11 months) with all patients still currently benefiting from gabapentin. We
      conclude that gabapentin may be an effective treatment for OT. Further trials are
      indicated.

PMID- 9756155
TI  - Disordered locomotion in the AS/AGU mutant rat and the effects of L-dopa or fetal
      midbrain grafts.

PMID- 9756156
TI  - An akinetic-rigid syndrome, depression, and stereotypies in a young man.
AB  - A young man is presented who developed an akinetic-rigid syndrome shortly after a
      minor illness. Rituals and stereoptypies were prominent. At its most severe he
      was unable to feed himself. There was no response to L-dopa/cardopa treatment. A
      course of ECT was followed by a marked improvement in his condition. Attempts to
      stop ECT for more than a week have led to recurrence of his bradykinesia.

PMID- 9756157
TI  - Treatment of hereditary trembling chin with botulinum toxin.

PMID- 9756158
TI  - A case of tardive tremor successfully treated with clozapine.

PMID- 9756159
TI  - Theophylline-induced stuttering.

PMID- 9756160
TI  - Complex movement disorder associated with fluvoxamine.

PMID- 9756161
TI  - New use for an old drug: amantadine benefits levodopa-induced dyskinesia.

PMID- 9756162
TI  - P450 enzymes and Parkinson's disease.

PMID- 9756163
TI  - Intranuclear neuronal inclusions in DRPLA.

PMID- 9756164
TI  - Cerebral hypoperfusion and hypometabolism in chorea-acanthocytosis.

PMID- 9756166
TI  - Modelling the enhancement of fractionated radiotherapy by gene transfer to
      sensitize tumour cells to radiation.
AB  - BACKGROUND AND PURPOSE: Several strategies now exist for the use of gene transfer
      methodologies to sensitize tumour cells to radiation. These include the
      transfection of genes synthesizing cytokines, p53 gene replacement and methods
      based on the use of HSV-tk and gancyclovir. Very recently, the sequencing of
      radioprotector or repair genes, such as ATM, Ku80 and XRCC2, has made it possible
      to consider the design of gene transfer strategies resulting in protector gene
      knock-out. Selectivity of transfected gene expression might be achieved by use of
      tissue-specific promoters or by the trophism of viral vectors. The purpose of
      this study was to evaluate the probable efficacy of such strategies. METHODS: We
      have modelled gene transfer-mediated radiosensitization of tumour cells during
      radiotherapy, focusing on anti-protector gene strategies, to explore the role of
      transfection frequency, sensitizing efficacy, transfection stability,
      untransfectable subpopulations, the timing of gene therapy and the treatment
      schedule structure. RESULTS: We predict a substantial therapeutic benefit of gene
      transfer treatment (with at least weekly transfection) which modifies cellular
      radiosensitivity by a factor of 1.5 or more, despite modest efficiency of
      cellular transfection (e.g. 50%), transient retention of the transfected gene
      (e.g. 2-day half-life) and the existence of a small minority (e.g. 1%) of
      untransfectable cells. CONCLUSIONS: The analysis shows repeated administration of
      gene transfer treatment to be obligatory and implies that the existence of
      untransfectable minority subpopulations (i.e. cells inaccessible to the vector)
      will be the major limiting factor in therapy. Experimental work is needed to
      confirm these predictions before clinical studies begin.

PMID- 9756165
TI  - Hyperthermic isolated limb perfusion with tumour necrosis factor and melphalan as
      treatment of locally advanced or recurrent soft tissue sarcomas of the
      extremities.
AB  - Hyperthermic isolated limb perfusion (HILP) with various chemotherapeutic agents
      has been used for the local treatment of high-grade soft tissue sarcomas (STS) of
      the extremities, but in most cases with a disappointing result. Most regimens
      should certainly not be considered superior to surgery plus radiotherapy.
      Although the majority of extremity STS can be resected locally, some have a very
      large size and are in close proximity to bones, nerves or blood vessels. In these
      cases, amputation is the only means of resecting the tumour. A new combination of
      drugs used in the set-up of HILP with tumour necrosis factor-alpha and melphalan
      has emerged as a very promising option for the limb-saving management of locally
      advanced STS. In recent studies, complete response rates of approximately 30% and
      partial remission rates of 50% have been achieved, while the overall limb-salvage
      rate is more than 80%.

PMID- 9756167
TI  - Radical radiotherapy for carcinoma of the oesophagus: an effective alternative to
      surgery.
AB  - BACKGROUND AND PURPOSE: Despite advances in operative and postoperative care,
      long term survival rates following radical oesophagectomy are poor. Surgery
      remains the mainstay of radical treatment despite various series reporting
      similar results for treatment with radiotherapy, in particular in the upper third
      of the oesophagus. We have studied a cohort of patients treated with definitive
      radiotherapy to examine the influence on survival of changes in diagnostic
      scanning and radiotherapy computer planning as well as various patient and
      disease related prognostic factors. PATIENTS AND METHODS: From 1985 to 1994, 101
      patients with clinically localised carcinoma of the oesophagus were treated at
      the Christie Hospital with definitive radiotherapy. This included 11 patients
      with oesophageal adenocarcinoma. Diagnostic and planning techniques changed over
      the period studied, with increasing use of both diagnostic and radiotherapy
      planning CT scanning. Radiotherapy doses ranged from 45 to 52.5 Gy in 15 or 16
      fractions over 3 weeks. RESULTS: The 3- and 5-year survival figures were 27% and
      21%, respectively, corrected for intercurrent deaths. Survival was better for
      adenocarcinoma than squamous cell carcinoma, though not statistically
      significantly. The only significant prognostic factor (P = 0.01) was the use of
      diagnostic CT scanning (42% versus 13% 5-year survival with or without diagnostic
      CT scanning, respectively) which was associated with an increase in field size.
      Radiotherapy was well tolerated with no acute mortality or significant morbidity.
      Late stenosis requiring oesophageal was seen in five of 20 patients surviving 3
      years or more. CONCLUSIONS: Survival following well planned radiotherapy is an
      effective alternative to surgery for both squamous cell and adenocarcinoma.
      Advances in staging and three-dimensional planning and the use of multimodality
      treatment may further improve survival.

PMID- 9756168
TI  - Haematological toxicity of cranio-spinal irradiation.
AB  - BACKGROUND: To assess the frequency and severity of myelosuppression due to
      cranio-spinal irradiation either alone or in combination with chemotherapy and to
      identify patients at high risk of haematological toxicity who may require
      supportive therapy. MATERIALS AND METHODS: Between 1965 and 1994, 210 patients
      received cranio-spinal axis (CSA) radiotherapy as a component of treatment for
      primary CNS tumours at the Royal Marsden Hospital. Full blood counts (FBC) were
      obtained before, during and after radiotherapy in 200 patients. Haematological
      toxicity was graded according to the WHO criteria and duration was measured from
      the onset of grades 3 and 4 toxicity until recovery to grade 2. RESULTS: Sixty
      six (33%) patients developed grades 3 and 4 haematological toxicity. Nadir
      occurred during radiotherapy and was most frequent during the second week of
      spinal radiotherapy. Low haemoglobin and white cell counts prior to radiotherapy
      increased the likelihood of myelosuppression. Nine patients had febrile episodes
      requiring antibiotic therapy. Treatment was interrupted in 49 patients but
      treatment time was extended beyond 12 weeks in only 17 (8%) patients of which
      nine were due to haematological toxicity. Chemotherapy (vincristine) during
      radiotherapy did not impact on haematological toxicity. Age and prior
      chemotherapy were independent predictive factors for haematological toxicity. The
      relative risk of leukopaenia in children compared to adults was 7.9 (95% CI 3.4
      18.6%). Patients who received prior chemotherapy had a relative risk of toxicity
      of 6.1 (95% CI 2.9-12.8%). CONCLUSION: One-third of patients undergoing CSA
      radiotherapy develop grades 3 and 4 haematological toxicity. The risk is higher
      in children and in patients who receive chemotherapy prior to radiation. There
      was no treatment-related mortality and only nine of 200 patients (9/60 of those
      with toxicity) required supportive treatment for neutropaenic sepsis. The low
      incidence severe haematological toxicity does not warrant routine use of
      haemopoietic growth factors during CSA irradiation and future studies should
      target high risk subgroups.

PMID- 9756169
TI  - Reduced incidence of the somnolence syndrome after prophylactic cranial
      irradiation in children with acute lymphoblastic leukemia.
AB  - A prospective double blind randomized trial comparing two different dose
      schedules of continuous steroid coverage during prophylactic cranial radiotherapy
      (CRT) in leukemic children was conducted to find out the optimum dose to be
      prescribed to reduce the incidence of Somnolence Syndrome (SS). Between April
      1994 and February 1996, 32 patients with acute lymphoblastic leukemia received
      CRT of 18 Gy in 10 fractions. Patients were randomized to receive oral
      dexamethasone of 2 or 4 mg/m2 during radiotherapy. The diagnosis of SS was made
      clinically based on symptoms of somnolence. All patients were followed for a
      minimum of 8 months. The overall incidence of SS was 40%. The development of SS
      was steroid dose dependent. In low dose steroid arm the incidence of SS was 64.3%
      (9/14), compared to 17.6% (3/17) in high dose arm with statistically significant
      difference (P = 0.008). The median time to development of SS was 4 weeks. The
      most common symptom of SS was drowsiness followed by anorexia, headache, nausea,
      vomiting, decreased activity, irritability, fever and ataxia, respectively. The
      duration of symptoms ranged from 2 to 14 days. The development of SS was not
      related to the presence of acute reactions, age at the time of CRT and sex. In
      all cases the symptoms subsided completely and spontaneously. Our results suggest
      that steroid coverage at a dose of 4 mg/m2 during CRT reduces the incidence of
      SS. However, a multicentric prospective randomized trial is needed to determine
      the role and the optimal dose of steroid.

PMID- 9756170
TI  - Dose-effect relations for early local pulmonary injury after irradiation for
      malignant lymphoma and breast cancer.
AB  - PURPOSE: To quantify the influence of treatment- and patient-related factors on
      the severity of early local pulmonary injury and to establish whether regional
      differences are present for local dose-effect relations for early radiation
      induced pulmonary injury. METHODS: Forty-two patients with malignant lymphoma and
      40 breast cancer patients were examined prior to and 3 months after radiotherapy.
      The lymphoma patients were irradiated with mantle fields to an average dose of 38
      Gy and the breast cancer patients were irradiated with internal mammary node
      fields with or without tangential breast fields to an average dose of 50 Gy. Dose
      effect relations for local perfusion, ventilation and density changes were
      determined using correlated single photon emission computed tomography (SPECT)
      and CT data. A multivariate analysis was performed to study the influence of
      irradiated volume, chemotherapy (CMF and MOPP/ABV), smoking, age and gender. In
      addition, dose-effect relations for different regions in the lung were
      determined. RESULTS: A similar and almost linear increase of early functional
      changes as a function of radiation dose was observed for perfusion and
      ventilation, whereas the shape of the dose-effect relation and the magnitude of
      early structural changes were different for density. For the three end-points
      studied, regional differences in radiosensitivity could not be demonstrated. For
      the posterior lung region compared to the anterior lung region, however, a
      difference was observed, which could be attributed to a gravity-related effect in
      the measuring procedure. Local structural changes (density) were significantly
      smaller for smokers (P = 0.002) and young patients (P = 0.007), whereas the CMF
      chemotherapy regimen given after radiotherapy (P = 0.017) significantly increased
      the amount of functional changes (perfusion). The magnitude of local pulmonary
      changes was independent of the irradiated volume, the MOPP/ABV chemotherapy
      regimen and gender. CONCLUSION: The dose-effect relations for early radiation
      induced local pulmonary changes were independent of the irradiated volume,
      MOPP/ABV, gender and lung region. CMF, smoking and age influenced the magnitude
      of early pulmonary changes and should be taken into account in dose-escalation
      protocols.

PMID- 9756171
TI  - Lethal pulmonary toxicity after autologous bone marrow transplantation/peripheral
      blood stem cell transplantation for hematological malignancies.
AB  - BACKGROUND AND PURPOSE: Retrospective evaluation of the incidence of lethal
      pulmonary complications (LPC) with special emphasis on interstitial pneumonia
      (IP) in a large group of patients homogeneously treated with hyperfractionated
      total body irradiation (HTBI) before autologous bone marrow transplantation
      (ABMT) or peripheral blood stem cell transplantation (PBSCT) for hematological
      malignancy. The factors influencing IP are discussed. MATERIALS AND METHODS: Of
      260 patients (maximum follow-up 137 months) that were treated with ABMT or PBSCT
      for hematological neoplasms between 1982 and 1994, 209 patients received HTBI and
      could be evaluated with respect to lethal pulmonary complications and especially
      lethal interstitial pneumonia. For most patients (n = 155), the HTBI dose was
      14.4 Gy (lung dose 9-9.5 Gy) given in 12 fractions over 4 days. Twenty-one
      patients received a total dose of > or =15 Gy with pulmonary doses of 9-10.5 Gy.
      RESULTS: The actuarial overall 5-year survival for all 209 patients evaluated was
      44 +/- 4%, enabling valid evaluation with respect to lethal pulmonary toxicity.
      The actuarial incidence of all LPC during the first year was calculated as being
      8 +/- 2%. The actuarial incidence of lethal IP is certainly lower and was
      estimated to be between 3 and 5% for all patients. The overall treatment-related
      mortality was 12% in 188 patients that received a total dose of <15 Gy and 24%
      among the patients treated with a total dose of > or =15 Gy. CONCLUSION:
      ABMT/PBSCT, like other transplant modalities without significant graft versus
      host disease (GvHD), has a low transplant-related mortality, a very small rate of
      overall LPC and a low incidence of lethal IP after HTBI. Doses up to 14.4 Gy with
      lung doses of 9-9.5 Gy can be administered safely. For total doses of > or =15 Gy
      with lung doses of 9-10.5 Gy, the risk of serious transplant-related
      complications cannot yet be finally assessed but such higher doses should be
      considered with caution because of the possibility of increasing toxicity in
      organs other than the lung.

PMID- 9756172
TI  - Regional dose response to pulmonary irradiation using a manual method.
AB  - PURPOSE: To better understand the dose dependence of radiation therapy (RT)
      induced changes in regional lung perfusion and tissue density, using a manual
      method to reduce inaccuracies that might be present in previously described
      automated methods. MATERIALS AND METHODS: Patients who were to receive RT for
      tumors in and around the thorax, wherein portions of healthy lung would be
      incidentally irradiated, were prospectively studied. Changes in regional
      perfusion and tissue density were assessed by comparison of pre- and post-RT
      single photon emission computed tomography (SPECT), lung perfusion scans and
      computed tomography (CT) scans, respectively. The three-dimensional dose
      distribution was calculated on the pre-RT CT scan and correlated to the other
      scans via image registration. Study volumes were defined by hand and individually
      visualized on pre- and post-RT scans. The manually generated dose response data
      were compared to data generated using automated methods. The relationship between
      CT density and SPECT perfusion was also determined. RESULTS: Thirteen patients
      with lung cancer were evaluated for changes in tissue density and 11 patients
      were evaluated for changes in regional perfusion at 12 months post-RT. In
      general, density increases with increasing regional dose, with marked changes at
      >60 Gy. Regional perfusion decreases with increasing regional dose. In the low
      dose regions, relative perfusion increases by 35% on average. Manually measured
      dose responses correlated well with those determined automatically. The
      relationship between regional perfusion and CT density indicates a wide range of
      perfusion over a narrow range of CT density, with markedly reduced perfusion at
      CT densities of > -600 and < -900 H. CONCLUSIONS: The manually generated CT
      density dose response data broadly agree with data previously generated using
      automated methods. The manually generated perfusion dose response data are in
      fairly good agreement with automated data, lending credibility to the accuracy of
      the automated methods. Regional perfusion is markedly diminished where CT density
      is outside the range of normal lung tissue.

PMID- 9756174
TI  - What margins should be added to the clinical target volume in radiotherapy
      treatment planning for lung cancer?
AB  - BACKGROUND: The planning target volume in radiotherapy treatment planning takes
      into account both movements of the clinical target volume (CTV) and set-up
      deviations. MATERIALS AND METHODS: A group of patients who received radiotherapy
      for lung cancer were studied. In order to measure the CTV movements due to
      respiration and other internal organ motions, fluoroscopy was performed for 20
      patients. To study the accuracy and reproducibility of patient and beam set-up,
      553 electronic portal images from 20 patients were evaluated. Discrepancies
      between planned and actual field positions were measured and the systematic and
      random errors were identified. The combined effect of these geometrical
      variations was evaluated. RESULTS: The average CTV movement with quiet
      respiration was about 2.4 mm in the medio-lateral and dorso-ventral directions.
      Movement in the cranio-caudal direction was on average 3.9 mm with a range of 0
      12 mm. The systematic set-up errors were on average 2.0 mm in the transversal
      plane and 3.0 mm in the cranio-caudal direction. The random errors can be
      described by their standard deviations of 3.2 and 2.6 mm. In this study, the
      combined effect of the two parameters (CTV movement and set-up deviations) varied
      between 7.5 and 10.3 mm in different anatomical directions. CONCLUSIONS: In our
      daily clinical routine, we use a margin of 11 mm in the transversal plane and 15
      mm cranially and caudally, also taking into account other unquantified variations
      and uncertainties.

PMID- 9756173
TI  - Evaluation of two dose-volume histogram reduction models for the prediction of
      radiation pneumonitis.
AB  - PURPOSE: To evaluate the similarities between the mean lung dose and two dose
      volume histogram (DVH) reduction techniques of 3D dose distributions of the lung.
      PATIENTS AND METHODS: DVHs of the lungs were calculated from 3D dose
      distributions of patients treated for malignant lymphoma (44), breast cancer (42)
      and lung cancer (20). With a DVH reduction technique, a DVH is summarized by the
      equivalent uniform dose (EUD), a quantity which is directly related to the normal
      tissue complication probability (NTCP). Two DVH reduction techniques were used.
      The first was based on an empirical model proposed by Kutcher et al. (Kutcher,
      G.J., Burman, C., Brewster, M.S., Goitein, M. and Mohan, R. Histogram reduction
      method for calculating complication probabilities for three-dimensional treatment
      planning evaluations. Int. J. Radiat. Oncol. Biol. Phys. 21: 137-146, 1991),
      which needs a volume exponent n. Several values for n were tested. The second
      technique was based on a radiobiological model, the parallel functional subunit
      model developed by Niemierko et al. (Niemierko, A. and Goitein, M. Modeling of
      normal tissue response to radiation: the critical volume model. Int. J. Radiat.
      Oncol. Biol. Phys. 25: 135-145, 1993) and Jackson et al. (Jackson, A., Kutcher,
      G.J. and Yorke, E.D. Probability of radiation-induced complications for normal
      tissues with parallel architecture subject to non-uniform irradiation. Med. Phys.
      20: 613-625, 1993), for which a local dose-effect relation needed to be
      specified. This relation was obtained from an analysis of perfusion and
      ventilation SPECT data. RESULTS: It can be shown analytically that the two DVH
      reduction techniques are identical, if the local dose-effect relation obeys a
      power-law relationship in the clinical dose range. Local dose-effect relations
      based on perfusion and ventilation SPECT data can indeed be fitted with a power
      law relationship in the range 0-80 Gy, from which values of n = 0.8-0.9 were
      deduced. These correspond to the commonly used value of n = 0.87 for lung tissue
      and yielded EUDn=0.87 values which were almost identical to the mean lung doses.
      For other n values, for which no experimental data are present, differences exist
      between EUD and mean dose values. Six patients with malignant lymphoma (6/44) and
      none of the breast cancer patients (0/42) developed radiation pneumonitis. These
      cases occurred only at high values for the mean lung dose. CONCLUSION: The two
      DVH reduction techniques are identical for lung and are very similar to mean dose
      calculations. The two techniques are also relatively similar for other model
      parameter values.

PMID- 9756175
TI  - The magnitude of treatment field set-up parameter correction in radiation
      therapy.
AB  - To achieve a better correction effect in radiation treatment, a correction
      (c(alpha)) is suggested which is optimal in the sense of minimal standard
      deviation of the residual systematic displacement (delta(r)) obtained after
      correction. To evaluate the improvement due to c(alpha), the performance of the
      original Bel's rule was compared to the performance of its modification, where
      same decision-making thresholds were used but a correction c(alpha) was applied.
      For this, 5000 treatment courses were simulated at different standard deviations
      (sigma(delta) and sigma(delta)) of the systematic displacement delta and random
      error delta. The experiments showed improved accuracy by up to 7% in terms of
      ?delta(r)? < or = 1.5 mm and also a reduced average number of corrections per
      patient of about 0.1 corrections.

PMID- 9756176
TI  - Quality assurance of physical parameters in radiation oncology at the University
      Hospital of Basel--a retrospect.
AB  - BACKGROUND AND PURPOSE: The necessity for and the benefit of a quality assurance
      program in radiation oncology are not questioned. Nevertheless, a retrospective
      analysis of the accumulated results of several years of quality assurance offers
      the possibility for further optimization. MATERIALS AND METHODS: The results of
      the physical quality control in radiation treatment planning and on radiation
      treatment units in the Institute for Radiation Oncology at the University
      Hospital of Basel for the years 1985, 1991 and 1994 are analyzed and compared
      mutually. The frequencies of the deviations from the nominal values for the
      different tests are stated. RESULTS: The relevance of the deviations for the
      different parameters is rated and the manifested influence of the type and age of
      the equipment on the results of the quality assurance is discussed. CONCLUSIONS:
      A condition for the maximum benefit gained from the quality assurance is the
      oncologist's understanding of the necessity for regular checks and the urgency
      for eliminating the established deficiencies. In that way the accuracy for the
      treatment planning, simulation and set-up process and for the realization of the
      radiation treatment can be increased and the methods can be improved.

PMID- 9756177
TI  - Treatment planning for radiotherapy in northern Italy: a survey by the National
      AIFB-AIRO Committee on 3D-Treatment Planning. Italian Association for Biomedical
      Physics. Italian Association for Radiation Oncology.
AB  - BACKGROUND AND PURPOSE: A survey was performed in 1996 to investigate the
      structures and the process of radiation therapy treatment planning in clinical
      practice within northern Italy, with particular emphasis on the current and
      future implementation of 3D equipment and techniques. MATERIALS AND METHODS: Of
      57 existing radiation therapy (RT) centres covering a population of 25 million
      people (45% of the total population of Italy) and treating over 58,000 cancer
      patients (70% of the cancer cases in Italy) each year, 46 centres were deemed
      eligible for the survey; a questionnaire was sent to a medical physicist working
      in each eligible RT centre, 40 of whom responded, making the basis for this
      report. RESULTS: A dedicated CT scanner was available in 25% of the responding
      centres and a total of 49 radiation therapy planning systems (RTPS) were
      reported; none of the RTPS were able to perform 3D calculations, but 50% of the
      centres had an advanced 2D or 2.5D system. Connection between CT scan and RTPS
      was by tape or disk in 62% of centres. Immobilization devices were used
      frequently for head and neck patients (88% of centres), but not for lung (16%) or
      prostate cancer (24%) patients; the number of contoured slices was largely
      variable, exceeding 10 in only about 30% of the responding centres. The average
      working time per patient seemed to closely reflect the number of slices used and
      the number of critical organs contoured. Finally, the majority of the responding
      physicists did not favour the use of more than 20 CT slices for 3D treatment
      planning, nor did they forecast a general spread of this technique in the next 2
      3 years. CONCLUSIONS: This survey has shown (1) a heterogeneous picture, with 20%
      of centres ready to implement 3D techniques and 20% of centres lacking the
      possibility of planning treatments and (2) a general difficulty in coping with
      the workload represented by 3D treatment planning.

PMID- 9756178
TI  - A dosimetric intercomparison of kilovoltage X-rays, megavoltage photons and
      electrons in the Republic of Ireland.
AB  - BACKGROUND AND PURPOSE: A comprehensive dosimetry intercomparison has been
      carried out involving all the radiotherapy centres, all external beam modalities
      and every radiotherapy treatment unit in the Republic of Ireland. MATERIALS AND
      METHODS: Reference point measurements were made for all megavoltage photon beams.
      Doses were also investigated in planned three-field distributions. One of these
      was in a homogeneous epoxy resin solid water phantom, whilst the second included
      a lung equivalent insert. The intercomparison was also carried out for three
      electron energies in each centre. The position of the depth of maximum dose for a
      standard field size was independently determined, as was the beam energy and a
      subsequent beam calibration was made. In addition, a kilovoltage X-ray
      intercomparison was carried out on every kilovoltage quality. RESULTS: For 13
      megavoltage photon beams a mean ratio of intercomparison measured dose to locally
      measured dose of 1.002 was obtained (standard deviation 1.2%). For 12 electron
      beam measurements a mean ratio of intercomparison measured dose to locally
      measured dose of 1.018 was obtained (standard deviation 0.8%). For four
      kilovoltage beams a mean ratio of intercomparison measured dose to locally
      measured dose of 0.997 was obtained (standard deviation 1.9%). CONCLUSIONS: The
      intercomparison has given confidence in the basis of clinical delivery of
      radiation dose in radiotherapy treatment and in the consistency (precision) of
      dosimetry between different centres within the Republic of Ireland. In addition,
      it has established a methodology for subsequent ongoing routine radiotherapy
      dosimetry audit and a baseline set of results to act as an initial reference
      point.

PMID- 9756179
TI  - Consistency in quality control programmes for electron accelerators in
      radiotherapy centres.
AB  - BACKGROUND AND PURPOSE: To gain insight into the current practice of quality
      control (QC) of medical electron accelerators and to reduce possible variations
      in test frequencies and test procedures. MATERIALS AND METHODS: An extensive
      questionnaire on QC procedures of medical electron accelerators was distributed
      and completed by all (21) radiotherapy institutions in The Netherlands. The
      questions were related to safety systems, mechanical parameters, beam profiles,
      beam energy, absolute dosimetry, wedge filters, the dose monitor system and
      radiation leakage. The data of the questionnaire were compared with
      recommendations given in national and international reports on QC of electron
      accelerators. RESULTS: Large variations in time spent on QC exist, especially for
      accelerators having dual energy photon beams and several electron beam energies.
      This diversity is mainly due to differences in philosophy with regard to QC and
      the differences in resources and machine time available. Furthermore, large
      variations in test frequencies and test methodologies were observed. The staffing
      level involved in the QC measurements was evaluated and compared with recent
      recommendations provided by EFOMP-ESTRO. CONCLUSIONS: From these recommendations
      and the results of the questionnaire, a set of minimum guidelines for a QC
      programme could be formulated and implemented in all radiotherapy institutions in
      The Netherlands.

PMID- 9756180
TI  - Cytokines and their receptors as therapeutic targets in asthma.
AB  - Cytokines are very potent pro-inflammatory agents. Several cytokines are present
      in abnormal quantities in asthmatic airway tissues. In vitro and in vivo
      experiments demonstrate that these cytokines have biological effects relevant to
      the pathogenesis of asthma. We review the evidence that interleukin-4 (IL-4),
      interleukin-5 (IL-5), interleukin-10 (IL-10), interleukin-12 (IL-12) and
      interferon-gamma (IFNgamma) have the potential of playing a key role in the
      pathogenesis of asthma. Inhibition of the activity of IL-4 or IL-5 and enhancing
      or mimicking the action of IL-10, IL-12 or IFNgamma are therapeutic options in
      asthma that warrant further investigations.

PMID- 9756181
TI  - IgE-Fc epsilonRI-mast cell axis in the allergic cycle.
AB  - The IgE and allergen dependent activation of mast cells via the high affinity IgE
      receptor (Fc epsilonRI) resulting in the release of inflammatory mediators is
      critical to the pathogenesis of atopic diseases like bronchial asthma and
      allergic rhinitis. However, mast cells are also involved in certain IgE
      independent biological responses, and recent studies have highlighted the role of
      mast cells in host defense. In the light of this background, we have discussed
      our recent data on the immunophenotypic characteristics of nasal mast cells in
      patients with perennial allergic rhinitis (PAR) and chronic infective rhinitis
      (CIR) based on the expression of cytokines, the Fc epsilonRI, the cell-bound IgE,
      as well as the IgE-mediated mediator release (before and after saturation of the
      IgE receptors). Although nasal mast cells (NMC) from both groups of patients
      expressed a variety of cytokines, significant differences were observed in the
      proportion of cytokine expressing cells between PAR and CIR. NMC from PAR
      patients exhibited increased Fc epsilonRI expression, cell-bound IgE and IgE
      mediated mediator release as compared with NMC from CIR patients, even after
      saturation of the IgE receptors. The density of IgE receptors and IgE molecules
      in NMC of PAR patients correlated well with the levels of serum IgE, and IL-4
      upregulated the expression of the Fc epsilonRI in NMC. Moreover, NMC from PAR
      patients induced IgE synthesis in B cells. Taken together, these results and the
      recently demonstrated IgE-induced upregulation of the Fc epsilonRI expression in
      mast cells suggest critical roles for mast cells in promoting the allergic
      reaction through an IgE-Fc epsilonRI-mast cell axis.

PMID- 9756182
TI  - The role of adhesion molecules in allergic inflammation and their suitability as
      targets of antiallergic therapy.
AB  - Adhesion molecules on leukocytes and tissue-resident cells are now known to
      mediate steps of the allergic inflammation response. Blockade of adhesion
      pathways is being actively explored as a potential strategy to therapeutically
      manage allergic diseases. The various adhesion molecules and their counterligands
      are discussed with respect to evidence supporting their role in allergic
      inflammation and suitability as therapeutic targets.

PMID- 9756183
TI  - The role of theophylline and phosphodiesterase4 isoenzyme inhibitors as anti
      inflammatory drugs.
AB  - Theophylline has been used for over a century in the treatment of asthma and
      while it is used principally as a bronchodilator, a number of recent studies have
      demonstrated potential anti-inflammatory and immunomodulatory activity. Indeed,
      regular treatment with low-dose theophylline, affords significant clinical
      benefit at the expense of unwanted side-effects associated with this drug,
      including headache and vomiting. The mechanism of action of theophylline is
      unclear, although a significant body of evidence points to an involvement of
      phosphodiesterase enzyme inhibition. Phosphodiesterases are a diverse group of
      enzymes that belong to at least seven families and of particular interest is the
      role of phosphodiesterase 4 isoenzyme as it is distributed in a number of
      inflammatory and immune cells and whose inhibition results in the downregulation
      of inflammatory and immune cell function. The discovery of pharmacological drugs
      selective for this isoenzyme has been viewed with interest in light of the
      positive results from preclinical and early clinical studies. Whether orally
      active safe phosphodiesterase 4 isoenzyme inhibitors will be useful in the
      treatment of asthma remains to be established.

PMID- 9756184
TI  - Theophylline and airway inflammation.
AB  - The view of theophylline as a second-line bronchodilator in asthma therapy has
      begun to be reconsidered in recent years as the details of its additional actions
      on airway inflammation have emerged. Increasing understanding of the mechanisms
      of action of theophylline has led to an appreciation of the ways in which this,
      and other related drugs, may influence the development and maintenance of the
      airway inflammation that underlies asthma through alteration of inflammatory cell
      function. In addition, recent demonstrations that theophylline can suppress late
      phase asthmatic reactions at serum concentrations below those traditionally
      regarded as therapeutically useful have provided evidence that theophylline's
      beneficial actions in asthma extend beyond mild bronchodilation. The apparent
      suppression of airway inflammation by theophylline in asthmatic patients
      reinforces data from ill vitro experiments, showing inhibitory actions of
      theophylline on the pro-inflammatory functions of many immune cells. Here, we
      review some recent advances in the understanding of theophylline's actions that
      suggest its role as an anti-inflammatory drug in asthmatic airways.

PMID- 9756185
TI  - Asthma, adenosine, mast cells and theophylline.
AB  - Many clinical trials have suggested that theophylline has anti-inflammatory
      properties in the treatment of bronchial asthma. Proposed mechanisms of
      theophylline inhibition include phosphodiesterase inhibition, an adenosine
      receptor antagonist, the increase of circulating adrenaline, mediator antagonist
      and inhibition of calcium ion influx. Further to these observations we report on
      the inhibition by theophylline of NF-kappaB, a key transcription factor found in
      human purified mast cells, which plays a role in the transcription of TNF alpha,
      GM-CSF, and IL-8 within this cell. The suppression of NF-kappaB activation,
      indicates that theophylline, in addition to its bronchodilator activities, has
      the potential for anti-inflammatory activity.

PMID- 9756186
TI  - Theophylline inhibits the release of eosinophil survival cytokines--is Raf-1 the
      protein kinase A target?
AB  - Increased numbers of activated eosinophils in bronchial tissue is a feature of
      asthma and may, in part, be attributed to the prolonged cytokine-dependent
      survival of eosinophils within the inflamed microenvironment. Low-dose oral
      theophylline was previously shown to reduce the number of activated eosinophils
      within the sub-mucosa following allergen exposure. A number of inhibitory actions
      of theophylline have been described which relate to eosinophil recruitment and
      activation, including inhibition of cell migration and release of granule basic
      proteins. In this study we investigated the ability of theophylline to inhibit
      the release of preformed GM-CSF and IL-8 from eosinophils in vitro, as these
      cytokines may serve an autocrine function in eosinophil survival in vivo.
      Eosinophils rapidly released GM-CSF and IL-8 spontaneously, and release was
      further enhanced in response to sIgA-coated beads. Theophylline inhibited the
      stimulated, but not the spontaneous, release of both cytokines. We previously
      reported the role of protein kinase A in inhibition of arachidonic acid
      mobilization and LTC4 synthesis. Therefore we speculate that cAMP-dependent
      activation of protein kinase A following theophylline treatment of eosinophils
      resulted in inhibition of Raf-1 and MAPK/MAPKK dependent activation of
      phospholipase A2 and consequently inhibition of degranulation and cytokine
      release.

PMID- 9756187
TI  - Therapeutic activities of theophylline in chronic obstructive pulmonary disease.
AB  - Recent observations in asthmatics demonstrated anti-inflammatory and
      immunomodulatory activities of theophylline besides the bronchodilating effect.
      Theophylline inhibits the mediator release from mast cells, peripheral blood
      monocytes and alveolar macrophages. The proliferative response of T-cells as well
      as the influx of eosinophils in BAL fluid is inhibited by treatment with
      theophylline. The production and release of pro-inflammatory cytokines are
      affected by theophylline showing a potent inhibitory effect on the production of
      IL-1beta, TNF-alpha and IFN-gamma. The production of the anti-inflammatory
      cytokine IL-10 is increased. Evidence is mounting that the anti-inflammatory
      effects and immunomodulating actions are exerted at lower plasma concentrations
      than those required for bronchodilation. These activities are of relevance in the
      treatment of chronic obstructive pulmonary disease (COPD), a disease in which the
      inflammatory component is considered to be more important than previously
      thought.

PMID- 9756188
TI  - Effect of theophylline withdrawal on airway inflammation in asthma.
AB  - Theophylline has been used as a bronchodilator in acute and chronic asthma
      management, although there is accumulating evidence that it may have anti
      inflammatory effects. We have investigated the effect of theophylline withdrawal
      for 6 weeks in asthmatic subjects whose peak expiratory flow (PEF) readings were
      more than 80% of the predicted value and its variability was less than 20% (Green
      Zone) by treatment with both a moderate dose of inhaled corticosteroids (BDP),
      400-800 microg/day) and low dose theophylline (400 mg/day) for more than 3
      months. In 38 asthmatic subjects, changes in clinical symptoms, respiratory
      function and airway inflammation detected with hypertonic saline induced sputum,
      and airway reactivity to histamine were investigated. One half of the patients
      were randomly withdrawn from theophylline, while the other half continued to take
      the same dose of theophylline for a period of 6 weeks. Mean steady state plasma
      theophylline concentrations when receiving treatment with theophylline were 8.08
      microg/mL in the theophylline withdrawal group and 7.64 microg/mL in the control
      theophylline group, respectively. Although a significant increase in asthma
      symptoms emerged in the theophylline group, there were no significant changes in
      the theophylline administration group. In the theophylline withdrawal group,
      there were small but significant falls in PEF in the morning, FEV1 and V50 at the
      end of the study period. Analysis of induced sputum showed that there was also a
      significant increase in the percentage of total and activated (EG2+) eosinophils
      only in those patients who withdrew from theophylline. These results indicate
      that chronic treatment with low dose theophylline exerts an anti-inflammatory
      effect and that the additional use of theophylline with inhaled corticosteroids
      provides an effective treatment for moderate asthma. Taken together, we conclude
      that theophylline has long-term beneficial effects on the chronic asthma
      management.

PMID- 9756189
TI  - Nocturnal asthma and the use of theophylline.
AB  - The nocturnal worsening of asthma is a common event in asthma patients. Some
      studies have shown the prevalence of nocturnal asthma to be as high as 75% of
      patients. It is important to understand this phenomenon as nocturnal asthma is
      associated with decreased daytime cognitive function and increased morbidity and
      mortality. The exact mechanism for decrements in overnight lung function is not
      known. However, there are many different processes associated with nocturnal
      asthma. Day-to-night change in both circulating bronchodilating and
      bronchoconstricting mediators occur which favour airway narrowing and increased
      bronchial hyperresponsiveness at night. The beta2 adrenergic receptors decrease
      in both number and function at night which is associated with a genetic
      polymorphism, a glycine 16 substitution. Neuroinfluences such as increased
      nocturnal cholinergic tone also contribute to nocturnal asthma, and a hallmark of
      nocturnal asthma is increased airway inflammation during sleep. Long-acting
      theophylline preparations have long been associated with improvement in overnight
      lung function. Some of these agents can be used in a chronotherapeutic modality,
      that is, higher blood levels at night when the disease is worse and lower blood
      levels during the day when lung function is routinely better. Theophylline works
      as both a bronchodilator and an anti-inflammatory agent to improve nocturnal
      asthma.

PMID- 9756190
TI  - Can we predict atopic disease using perinatal risk factors?

PMID- 9756191
TI  - Which is the true regulator of TH2 cell development in allergic immune responses?

PMID- 9756192
TI  - Immunotherapy--anergy, deviation or suppression?

PMID- 9756193
TI  - Restoration of cytokine imbalance by immunotherapy.

PMID- 9756194
TI  - The pathogenesis of nocturnal asthma in childhood.

PMID- 9756195
TI  - Asthma and respiratory syncytial virus infection in infancy: is there a link?

PMID- 9756196
TI  - Perinatal risk factors for atopic disease in conscripts.
AB  - BACKGROUND: There is evidence to suggest that atopic disease in adulthood could
      be manifestations of events in early life. OBJECTIVES: To investigate the
      relationship between perinatal risk factors and the prevalence of allergic
      rhinitis and asthma in conscripts. METHODS: A retrospective cohort study, where
      information from the Military Service Enrolment Register was linked to the
      national Medical Birth Register. The study included 149 398 male conscripts who
      were born in Sweden in 1973, 1974 and 1975. Outcome measures were current asthma
      and allergic rhinitis recognized at the compulsory military conscript
      examinations. RESULTS: Unifactorial analyses demonstrated that number of older
      siblings, young maternal age, multiple gestation, prematurity, low birth weight,
      growth retardation and perinatal asphyxia were all significantly related to a
      decreased risk of allergic rhinitis among male conscripts. The prevalence rates
      of allergic rhinitis among conscripts with and without older siblings were 14.1%
      and 16.2%, respectively (odds ratio 0.85; 95% confidence interval 0.82-0.87). The
      prevalence rates of allergic rhinitis among those with term birth (>36 weeks),
      moderately preterm birth (33-36 weeks) and very preterm birth (<33 weeks) were
      15.2%, 13.1% and 11.6%, respectively. Older siblings, multiple gestation and
      young maternal age were highly significant independent determinants of allergic
      rhinitis. By contrast, the effects of prematurity, low birthweight and asphyxia
      were weaker and highly correlated. The only independent determinants of asthma
      were maternal age, birthweight and multiple gestation. Furthermore, maternal age
      and birthweight had opposite effects on asthma and allergic rhinitis.
      CONCLUSIONS: In contrast to asthma, allergic rhinitis in young adult men was
      strongly associated with perinatal events. This may reflect the close
      relationship between allergic rhinitis and atopic sensitization, whereas asthma
      has a more multifactorial aetiology.

PMID- 9756197
TI  - Comparison between the in vitro cytokine production of mononuclear cells of young
      asthmatics with and without immunotherapy (IT)
AB  - BACKGROUND: The underlying mechanisms of immunotherapy (IT) are still unknown but
      may be related to modifications of cytokine production of T lymphocytes.
      OBJECTIVE: In this study we determined the in vitro allergen-induced production
      of IL-2, IL-4, IL-5, IL-12 and IFNgamma of peripheral blood mononuclear cells
      (PBMC) of eight young asthmatics, aged 15+/-2 years, receiving IT (IT group) and
      of eight comparable asthmatics, aged 13+/-3.5 years, who never received IT (non
      IT group). METHODS: All patients suffered from perennial asthma and were allergic
      to house dust mite (HDM). They were selected if they showed a positive
      stimulation index (SI) of PBMC after in vitro incubation with HDM (i.e. SI > 2).
      Cells were incubated with and without HDM (10 microg/mL) during 24 h, 48 h and 7
      days. Cytokines were determined in the supernatant at the three time points and
      are expressed as median values in pg/mL. RESULTS: In the IT group the secretion
      of IL-2 was lower compared with the non-IT group after 7 days incubation of PBMC
      with HDM (0 vs 33.2, P = 0.008). In both groups maximal secretion of IL-2 was
      observed after 48 h. In the non-IT group a high value of IL-2 persisted after 7
      days, whereas in the IT group a significant decline of IL-2 occurred after 7
      days. Although IL-4 secretion was low in all subjects, more patients of the non
      IT group showed detectable IL-4 in the HDM cultures after 24 h and 48 h, although
      the difference was not statistically significant (P = 0.08 and P = 0.28,
      respectively). Furthermore, IL-4 secretion was lower in the HDM cultures after 24
      h in the IT group (1.75 vs 4.1, P = 0.011) and 48 h (2.2 vs 4.1, P=0.035). IL-5
      secretion was lower in the HDM cultures after 24h (12.4 vs 47.6, P = 0.035) and
      48 h (26.8 vs 135, P = 0.046) in the IT group than in the non-IT group. After 7
      days of incubation with HDM there was no difference between the groups. There was
      no difference between both groups in secretion of IFNgamma and IL-12.
      CONCLUSIONS: These results show a difference in vitro cytokine secretion of PBMC
      of asthmatics receiving IT compared with asthmatics who never received IT. PBMC
      of patients receiving IT secrete less IL-2 and IL-5 after in vitro incubation
      with HDM and show a tendency to secrete less IL-4. The efficacy of IT may be
      attributed to a modified cytokine secretion of PBMC.

PMID- 9756198
TI  - Impaired NK1.1+ T cells do not prevent the development of an IgE-dependent
      allergic phenotype.
AB  - BACKGROUND: The induction of TH2 immune responses is critically dependent on
      initial IL-4. Although crucial, the source of this early IL-4 has not been
      identified. One candidate is a CD1 restricted NK1.1+ T cell subpopulation which
      is known to produce such early IL-4. OBJECTIVES AND METHODS: The necessity of
      NK1.1+ T cells for the expression of an IgE-dependent phenotype was investigated
      in a NK1.1+ T cell deficient mouse model. The allergic phenotype was defined as
      immediate cutaneous hypersensitivity. It was induced by immunization of mice with
      ovalbumin. Mouse strains used were C57BL/6 mice and C57BL/6 mice homozygous for a
      targeted mutation of the beta2 microglobulin gene with consecutive loss of CD1
      expression, which leads to a drastic reduction of NK1.1+ T cells. Manifestation
      of an allergic sensitization was assessed by intradermal allergen challenge after
      i.v. injection of Evans blue solution. The blue stained weal formations were
      quantified with the Bonitur method. In addition, the Th2 response was confirmed
      by the measurement of cytokines and serum immunoglobulins. The capability to
      produce early IL-4 was tested through the assessment of IL-4 mRNA shortly after a
      single challenge. RESULTS: Wild type and mutated mice did not differ in any of
      the immunological parameters measured. CONCLUSION: A single exposure to antigen
      with or without adjuvant induces early IL-4 production in C57BL/6 beta2m-/- mice.
      This early IL-4 is therefore independent of the presence of NK1.1+ T cells and
      functional MHC class I molecules and leads to IgE production and immediate
      cutaneous hypersensitivity.

PMID- 9756199
TI  - Prevalence and determinants of house dust mite allergen in East German homes.
AB  - BACKGROUND: In 1990/91, allergic sensitization to house dust mites (HDM) and
      other allergens was more prevalent in children from West Germany than from East
      Germany. OBJECTIVE: To test the hypothesis that low indoor exposure to HDM
      allergen in East Germany has contributed to this difference. METHODS: HDM
      allergen concentrations were determined in 634 East German dwellings shortly
      after the German reunification. RESULTS: HDM group I allergen (Der p 1 + Der f 1)
      levels in mattresses (median 2.16, geometric mean 2.07, maximum 278.9 microg/g
      dust) and carpets (median 0.41, geometric mean 0.48, maximum 96.3 microg/g dust)
      were within the range of levels determined in West Germany in other studies. One
      particular East German type of dwelling (light concrete buildings) was associated
      with lower mite allergen exposure, but only a minority of the population lived
      there. Coal heating, installed in the majority of dwellings before 1989, was
      associated with higher allergen exposure. Higher relative humidity (RH) was a
      main risk factor for higher Der p 1 exposure (odds ratio [OR] for exposure to >
      0.05 microg/g dust on carpets: 1.4 [95% confidence interval (CI) 1.2-1.8] for +
      10% RH) but not for higher Der f 1 exposure. Higher temperature was associated
      with a lower risk for elevated Der p 1 levels (> 0.05 microg/g dust on carpets):
      OR 0.6 (95% CI 0.5-0.8) for + 2 degrees C. CONCLUSION: Mite allergen exposure is
      not lower in East Germany than in West Germany. The data does not support the
      hypothesis, that low HDM allergen exposure in East Germany is a cause for the
      lower prevalence of HDM sensitization in East German children.

PMID- 9756200
TI  - Atopic dermatitis in early infancy predicts allergic airway disease at 5 years.
AB  - BACKGROUND: Screening tests for atopy risk in newborns have a low predictive
      value. If early atopic symptoms and signs could be used as predictors for the
      next expected atopic disorder then secondary prevention could be employed. The
      aim of this study was to evaluate the capacity of early atopic dermatitis to
      predict aeroallergen sensitization and the manifestation of respiratory atopic
      disorders at 5 years of age. METHODS: 1314 children of a German prospective birth
      cohort study MAS-90 were followed from birth up to 5 years of age. Atopic
      dermatitis, asthma and rhinoconjunctivitis were diagnosed from symptoms and signs
      at physical examinations and by interviews of the parents. Blood was drawn at 1,
      2, 3, and 5 years of age. Aeroallergen sensitization was diagnosed by a specific
      IgE value of at least 0.35 kU/L (CAP class > or = 1) against any of five
      respiratory allergens (mite, cat, dog, birch, grass). RESULTS: Atopic dermatitis
      in the first 3 months was a risk factor for aeroallergen sensitization at 5
      years. The risk increased with a positive family history for atopic diseases.
      Seventy-seven per cent of children with two atopic parents and early atopic
      dermatitis were sensitized against aeroallergens at 5 years, i.e. could have been
      predicted in early infancy without any laboratory tests. Although these risk
      factors were also significantly associated with the manifestation of allergic
      airway disease, the positive predictive value for this outcome at age 5 years was
      not yet as high, i.e. 50%. CONCLUSION: Infants with very early signs of atopic
      dermatitis and a positive family history are candidates for early intervention
      measures against respiratory allergies.

PMID- 9756202
TI  - Allergenic relationship among four common and dominant airborne palm pollen
      grains from Eastern India.
AB  - BACKGROUND: Palm pollen grains are predominant aeroallergens in the tropics
      including India. Evidence of allergenic crossreactivity had been reported from
      various parts of the world on different families, e.g. Poaceae, Asteraceae, etc.
      No such information is available about the palm pollen of tropical countries.
      OBJECTIVES: The present study was undertaken to find out the allergenic
      relationship, if any, in four common and important palm pollen in India. METHODS:
      A 2-year aerobiological survey was carried out at Madhyamgram situated at the
      suburban fringe of Calcutta Metropolis using Burkard volumetric sampler to know
      the seasonal variation of Areca catechu, Borassus flabellifer, Cocos nucifera and
      Phoenix sylvestris among others. Skin-prick tests (SPT) were performed with the
      relevant pollen extracts on the respiratory allergic patients. Sera from the
      subjects were tested directly by ELISA for estimating the allergen specific IgE.
      ELISA inhibitions and dot blotting were performed with pooled patients sera and
      four palm pollen extracts to detect the cross-reactivity. RESULTS: Among 70
      patients, Areca catechu exhibited the maximum percentage (48.5%) of positive
      responses followed by Cocos nucifera (45.7%), Phoenix sylvestris (42.85%) and
      Borassus flabellifer (38.5%). On an average, 30-50% of the patients showed
      positive skin reactions and enhanced specific IgE level to more than one palm
      pollen extract. Further evidence of allergenic crossreactivity among the four
      palm pollen grains were provided by dot blotting and ELISA inhibition studies. In
      ELISA inhibition, a distinct inhibition was obtained with comparable amounts of
      the pollen extracts. CONCLUSION: The suburban aerobiological survey of Calcutta
      and SPT results confirmed that the relevant pollen types are significant
      contributors of aeroallergen load of the study area. ELISA inhibition studies
      with the pooled patients sera using antihuman IgE probe revealed the presence of
      shared allergenic components among the four palm pollen grains.

PMID- 9756201
TI  - Comparison of skin-prick test and specific serum IgE determination for the
      diagnosis of latex allergy.
AB  - BACKGROUND: Latex IgE-mediated hypersensitivity has been recognized as an
      international health problem. However, there is poor information on the
      efficiency of the diagnostic methods available. OBJECTIVE: The purpose of this
      study was to specify the efficiency of several diagnostic methods for latex
      allergy. METHODS: We designed a prospective study involving 50 adult patients
      with latex allergy, as diagnosed by a suggestive clinical history and a positive
      skin-prick test (SPT) to a latex extract. One control group of 50 subjects paired
      for age, sex, total IgE levels and latex exposure, and another control group of
      30 subjects with pollen allergy were used. A low-ammoniated natural-latex and
      several glove-latex extracts were elaborated. SPTs with these extracts, as well
      as with four different commercial-latex extracts were performed. Latex-specific
      serum IgE was determined by the CAP and the AlaSTAT methods. RESULTS: Diagnostic
      sensitivity was 98% for the natural-latex extract SPT, from 90% to 98% for the
      commercial-latex extract SPT, and from 64% to 96% for the glove-latex extract
      SPT. Diagnostic specificity of SPT was 100%, and no severe adverse reactions were
      observed during skin testing. With respect to the latex-specific serum IgE
      determinations, sensitivity was 86% for the CAP system and 84% for the AlaSTAT
      assay, and specificity was dependent on the population considered. CONCLUSION:
      SPT with natural latex extracts has shown a diagnostic efficiency close to 100%,
      significantly higher than that of latex-specific serum IgE determination.

PMID- 9756203
TI  - Expression of two isoforms of Lep d 2, the major allergen of Lepidoglyphus
      destructor, in both prokaryotic and eukaryotic systems.
AB  - BACKGROUND: The dust mite Lepidoglyphus destructor is a major cause of allergic
      diseases among farmers. We have previously cloned and sequenced two isoforms of
      the major allergen Lep d 2 (formerly designated Lep d 1) and found significant
      homology to group 2 allergens of the house dust mite species Dermatophagoides. We
      now report on the production and characterization of recombinant Lep d 2.
      OBJECTIVE: We have expressed both isoforms in two different expression systems; a
      eukaryotic system, baculovirus in insect cells and a prokaryotic system, E. coli.
      We have compared the two systems in regard to production yields and
      immunoreactivity of the recombinant allergens. METHODS: The complete cDNA
      including the natural leader sequence was cloned into the pBlueBacIII transfer
      vector, and the rLep d 2 was produced as a secreted protein in baculovirus. For
      the expression in E. coli, the cDNA was cloned into the pET vector, and the rLep
      d 2 was produced with six C-terminal histidine residues. The purified recombinant
      allergens were tested for immunoreactivity with 10 sera from subjects allergic to
      Lepidoglyphus destructor and were compared with native Lep d 2 using inhibition
      immunoblotting. The ability of the recombinant allergens to release histamine
      from basophils was evaluated using a histamine release assay. RESULTS: Both
      expression systems produced immunoreactive recombinant allergens. They inhibited
      the binding of human sera to native Lep d 2 confirming their retained IgE binding
      properties. The yield of pure recombinant protein from the prokaryotic system was
      approximately 1 mg/L compared to the eukaryotic system which produced up to 4
      mg/L in an adherent cell culture system. CONCLUSIONS: We have produced
      recombinant Lep d 2 in prokaryotic and eukaryotic expression systems which are
      comparable to the native allergen. Recombinant Lep d 2 might now be included in
      more extensive clinical studies to confirm its usefulness in the in vitro and the
      in vivo diagnosis of Lepidoglyphus destructor.

PMID- 9756204
TI  - Dysregulation of monocyte differentiation in asthmatic subjects is reversed by IL
      10.
AB  - BACKGROUND: IL-10 can modulate the differentiation of normal monocytes to
      macrophages, increasing the proportion of maturing cells with a phenotype
      consistent with T cell suppressive activity. Analysis of the immunopathology in
      endobronchial biopsies from asthmatic subjects has revealed significantly reduced
      proportions of suppressive macrophage populations associated with chronic T-cell
      mediated inflammation. OBJECTIVE: This study investigates whether the altered
      homeostasis within the lung macrophage populations in asthma is reflected in
      aberrant differentiation of peripheral blood monocytes and whether this
      differentiation may be influenced by IL-10. METHODS: Monocytes from 14 normal
      individuals and 14 atopic asthmatics were grown in culture for 7 days in the
      presence or absence of IL-10, added on day 5. Double immunofluoresence studies
      were performed on cytospins of the differentiated macrophages using the
      monoclonal antibodies RFD1 and RFD7 to distinguish inductive and suppressive
      macrophages by their respective phenotypes. HLADR expression was quantified using
      the monoclonal antibody RFDR1. Macrophage function was determined by quantifying
      allostimulation in a mixed leucocyte reaction and by measuring TNFalpha and
      TGFbeta production. RESULTS: With no cytokine addition the proportion of maturing
      macrophages with a suppressive phenotype (D1+D7+) at day 7 was lower in the
      asthmatic samples (18%) compared with normals (25%). IL-10 increased the
      proportion of suppressive cells in cultures of both asthmatic and normal
      monocytes with the increase in the asthmatic subjects (94% increase) being
      significantly greater than that in normal subjects (32% increase) (P<0.01).
      Asthmatic monocytes had a greater effect in stimulating MLR than normals (P <
      0.05) but the addition of IL-10 reduced T cell proliferation in an MLR to a
      equivalent level in both groups. CONCLUSIONS: These results suggest that a
      fundamental problem may exist in the differentiation of monocytes in asthma which
      may be reversed by IL-10.

PMID- 9756205
TI  - Inhibition of interleukin-5 mediated eosinophil viability by fluticasone 17
      propionate: comparison with other glucocorticoids.
AB  - BACKGROUND: Inhaled glucocorticoids are commonly employed to treat patients with
      asthma. Eosinophils are important effector cells in the pathogenesis of asthma,
      and, in vitro, glucocorticoids modulate eosinophil viability. OBJECTIVE: Using
      this glucocorticoid inhibition of eosinophil viability, we compared the in vitro
      potencies of several inhaled glucocorticoids with particular attention to
      fluticasone 17-propionate. METHODS: Eosinophils from normal or mildly atopic
      donors were purified, cultured with cytokines and glucocorticoids, and on day 4,
      after staining with propidium iodide, analysed by flow cytometry. RESULTS:
      Eosinophil viability was prolonged by interleukin (IL)-5 in a concentration
      dependent manner; in contrast, dexamethasone inhibited the IL-5 effect.
      Fluticasone 17-propionate, 1.0-1000 nM, also inhibited the IL-5 effect in a
      concentration-dependent manner; interestingly, at 0.1 nM fluticasone 17
      propionate modestly, but significantly, enhanced eosinophil survival. High
      concentrations of IL-5 and granulocyte-macrophage colony-stimulating factor
      essentially completely overcame the inhibitory effect of 1000 nM fluticasone 17
      propionate on eosinophil survival. In contrast, although interferon-gamma
      mediated eosinophil viability was inhibited by 1.0-1000 nM fluticasone 17
      propionate, this inhibition was not overcome by increased concentrations of
      interferon-gamma. Comparison of the glucocorticoid inhibition of eosinophil
      viability in the presence of 10 pg/mL IL-5 resulted in these drug IC50 values (in
      nM): fluticasone 17-propionate, 1.3; budesonide, 8.5; triamcinolone acetonide,
      25; flunisolide, 32; dexamethasone, 94; beclomethasone 17-monopropionate, 210;
      beclomethasone 17,21-dipropionate, 290; and hydrocortisone, >1000. CONCLUSION:
      Fluticasone 17-propionate's effect on cytokine-mediated eosinophil viability is
      similar qualitatively to other glucocorticoid preparations. However,
      quantitatively, fluticasone 17-propionate has the most potent suppressive effects
      on IL-5 mediated eosinophil viability among the currently available inhaled
      glucocorticoids in the United States.

PMID- 9756206
TI  - Phase-contrast microscopic studies using cinematographic techniques and scanning
      electron microscopy on IgE-mediated degranulation of cultured human mast cells.
AB  - BACKGROUND: Isolating human mast cells is a laborious procedure. Recently,
      cultured human mast cells raised from umbilical cord blood cells have become
      available. It is necessary to investigate whether IgE-mediated activation of
      these cells is mediated by exocytosis. OBJECTIVE: To verify IgE-mediated
      activation of these cultured human mast cells morphologically. METHODS: The mast
      cells were raised from human umbilical cord blood cells in the presence of stem
      cell factor and interleukin-6. IgE-sensitized cultured human mast cells were
      activated by anti-IgE, and morphological changes of the cells were examined under
      phase-contrast microscopy using cinematographic techniques and scanning electron
      microscopy. Histamine release from the cells was measured with high-performance
      liquid chromatography. RESULTS: Under the condition in which a significant
      histamine release was observed from the mast cells, phase-contrast microscopy
      showed that the cultured human mast cells became swollen and extruded granules.
      Scanning electron microscopy disclosed the extrusion of smooth and round bodies
      from pores formed on the activated mast cell surface. CONCLUSION: IgE-mediated
      histamine release from cultured human mast cells is accompanied by exocytosis
      morphologically, indicating that cultured human mast cells will help in studying
      the functional properties of human mast cells.

PMID- 9756208
TI  - Alimentary allergy to pork. Crossreactivity among pork kidney and pork and lamb
      gut.
AB  - BACKGROUND: A patient suffered from anaphylaxis after the ingestion of pork gut
      and kidney, but she tolerated pork meat. Clinical symptoms were also triggered
      upon intake of lamb gut. OBJECTIVE: To demonstrate an IgE-mediated
      hypersensitivity and identify the pork proteins involved. And also, to study the
      possible cross-allergenicity among proteins from lamb gut and pork. METHODS AND
      RESULTS: The patient had strong positive skin-prick test responses to pork
      kidney, gut and liver, and lamb gut and kidney. RAST technique showed specific
      IgE to pork kidney, gut and meat. Immunoblotting after SDS-PAGE disclosed the
      presence of four prominent IgE-binding polypeptides in pork kidney (200, 90, 57,
      and 47 kDa), two in gut (57 and 27 kDa), and three in meat (51, 40, and 28-30
      kDa), apart from other weaker radiostained bands in each extract. The binding of
      IgE to 200 and 90 kDa allergens from pork kidney was inhibited by gut from pork
      and lamb in immunoblotting inhibition assays. No inhibition was produced by pork
      meat. CONCLUSIONS: A mechanism of IgE-mediated hypersensitivity has been
      demonstrated in this case of anaphylaxis provoked by pork products. Four main
      allergens were detected in pork kidney, two of which (200 and 90 kDa) share
      allergenic epitopes with proteins from pork and lamb gut. On the other hand, pork
      meat does not seem to have allergenic epitopes in common with pork kidney.

PMID- 9756209
TI  - Food allergy with monovalent sensitivity to poultry meat.
AB  - BACKGROUND: Allergy to poultry meat is only rarely covered in science. The few
      reports are usually related to patients allergic to eggs or bird feathers.
      OBJECTIVE: Two patients with a clear history of monovalent, ingestive allergy to
      chicken and turkey meat, without other food allergies, were analysed. The
      relevant allergens were to be identified by immunoblotting. METHODS: Both
      patients were evaluated with skin tests and specific IgE determination (CAP).
      Allergens were identified by SDS-PAGE and immunoblotting. Cross-reactivity of
      chicken and turkey meat was examined by IgE inhibition experiments. RESULTS: Skin
      tests and specific IgE were positive for chicken and turkey in both patients.
      Cross-reactivities to other poultry meats were documented for duck and goose
      meat. No sensitization to egg components or poultry feathers could be found.
      Allergenic proteins of poultry meat were detected at molecular weights of 21, 23
      and 50 kDa (distinct bands) and 13, 27 and 33kDa (faint bands). An additional
      band at 91 kDa for turkey, can probably not be considered a distinct allergenic
      epitope. Immunoblot inhibition confirmed cross-reactivity of chicken and turkey
      meat allergens. CONCLUSION: Food allergy to poultry meat is a distinct disorder
      with crossreactivity among chicken, turkey and other poultries. The relevant
      allergens were identified by immunoblotting. Associated food allergy to egg
      components is unlikely as the patients were able to tolerate egg and eggs
      products.

PMID- 9756207
TI  - Allergen challenge-induced extravasation of plasma in mouse airways.
AB  - BACKGROUND: Mouse models are extensively used to study genetic and immunological
      mechanisms of potential importance to inflammatory airway diseases, e.g. asthma.
      However, the airway pathophysiology in allergic mice has received less attention.
      For example, plasma extravasation and the ensuing tissue-deposition of plasma
      proteins, which is a hallmark of inflammation, has not been examined in allergic
      mice. OBJECTIVE: This study aims to examine the vascular permeability and the
      distribution of plasma proteins in mouse airways following exposure to allergen
      and serotonin. METHODS: Extravasated plasma was quantified by a dual isotop
      technique using intravascular (131I-albumin) and extrasvascular (125I-albumin)
      plasma tracers. Histological visualization of fibrinogen and colloidal gold
      revealed the tissue distribution of extravasated plasma. RESULTS: Allergen
      aerosol exposure (3% OVA, 15min) of sensitized animals resulted in a marked
      plasma extravasation response in the trachea (P < 0.01) and the bronchi but not
      in the lung parenchyma. A similar extravasation response was induced by serotonin
      (P<0.001). Extravasating vessels (assessed by Monastral blue dye) were identified
      as intercartilaginous venules. Extravasated plasma abounded in the subepithelial
      tissue but was absent in the epithelium and airway lumen. The allergen-induced
      response was dose-dependently inhibited by iv administration of formoterol (P <
      0.001), a vascular antipermeability agent. CONCLUSION: The present study
      demonstrates that serotonin and allergen challenge of sensitized mice increase
      airway venular permeability to cause transient extravasation and lamina propria
      distribution of plasma in the large airways. We suggest that the extravasation
      response is a useful measure of the intensity and the distribution of active
      inflammation

PMID- 9756210
TI  - Study of a case of hypersensitivity to lettuce (Lactuca sativa).
AB  - BACKGROUND: Allergic reactions to lettuce (Lactuca sativa) are not too frequent
      and few cases of systemic adverse reactions after its ingestion have been
      described. OBJECTIVE: We report a case of clinical sensitization to lettuce on a
      patient who presented mucocutaneous manifestations after its ingestion, with
      positive skin tests, histamine release test and serum specific-IgE to lettuce.
      The allergens responsible for this sensitization were also characterized by means
      of SDS-PAGE immunoblotting. MATERIALS AND METHODS: We performed skin tests,
      histamine release test, serum specific IgE determination and CAP inhibition with
      lettuce and mugwort (Artemisia vulgaris) extracts. An aqueous and enriched
      lettuce (from loose leaf type) extract was subjected to SDS-PAGE immunoblotting
      for determination of its IgE-binding components. RESULTS AND CONCLUSIONS: CAP
      inhibition showed antigenic community between lettuce and mugwort. Four protein
      bands from the lettuce extracts with molecular weights of 50, 43, 39 and 16 kDa
      exhibited IgE-binding properties.

PMID- 9756211
TI  - Is there a correlation between change and progress in nursing education?

PMID- 9756212
TI  - Is caring a virtue?
AB  - The significance of the question 'Is caring a virtue?' lies in the fact that both
      the ethics of virtue and the ethics of care have been proposed as alternatives to
      what may be termed 'bioethics'. The ethics of care has been of particular
      interest to nursing theorists, especially those who want to say that there is a
      body of distinctively nursing ethical theory which is different from bioethics.
      In answering the main question there are three supplementary aims: first, to
      explore the relationship between virtue ethics and the ethics of care, it is
      suggested that caring is not a virtue, but that the virtues involve caring
      correctly; second, to give a broad outline of what is meant by an ethics of
      virtue, including what it means to care correctly; and third, to examine
      implications of the theory for nursing.

PMID- 9756213
TI  - Health care reform and the transformation of nursing in Hong Kong.
AB  - Health care reform in Hong Kong in the 1990s has brought about dramatic change to
      the nursing discipline. This paper reports an ethnographic study which aimed at
      exploring the transformation of nursing in a regional hospital in Hong Kong
      during this period of reform. In the study, the restructuring of nursing work,
      its associated dynamics and resulting impacts upon the nursing profession were
      examined. A methodological triangulation approach to data collection encompassing
      interviews, participant observation and review of documents was used. The
      findings in this study suggest that the majority of nurses working in the case
      study hospital continue to be subject to medical dominance and are under
      management control. The emphasis on cost-effective care has however, fostered
      qualified nurses to claim more ownership of their professional judgement and
      autonomy. The health care reform has confirmed the status of two newly
      established groups of nurses, the nurse specialists and nurse managers. The
      development of the nursing profession is found to be closely connected to its
      work development. The preparation of the new generation of nurses, as revealed in
      this study, needs to emphasize the cognitive dimension of the professional
      competence. Some nurses need to be further educated in specialist practice and
      clinical management to maximize the contribution of nursing in health care
      delivery.

PMID- 9756214
TI  - Fund-holding and contracting for community nursing services: a selective review
      of the literature.
AB  - In the context of social, political and economic pressures fund-holding has been
      described as the 'wild card' in the Health Care Reforms in the United Kingdom of
      the 1990s. Set against an international drive to reform health care and increase
      the efficient and effective use of resources, fund-holding by general practice is
      seen as one means of enhancing the contribution of a primary care led National
      Health Service (NHS). It is advocated that a primary care led NHS will enhance
      and strengthen the position of nursing in the health care context. In order to
      fully exploit such a position it is argued that primary care nurses must adopt a
      systems view, recognizing broader strategic issues upon which to base marketing
      approaches to the contracting process.

PMID- 9756215
TI  - Emphasizing terminal care as district nursing work: a helpful strategy in a
      purchasing environment?
AB  - This paper describes how within a study on the experiences of district nurses
      since the introduction of general practitioner purchasing, participants were
      encouraged to describe and define the district nursing service. The
      identification of terminal care by district nurses and others as a significant
      and defining example of district nursing work is explored and the possible
      reasons for its emphasis over other aspects of patient care. The extent to which
      terminal care was used within contract and purchasing discussions to aid general
      practitioner understanding of district nursing work and achieve extra funding is
      described. The paper concludes by questioning the extent to which terminal care
      is a helpful and accurate representation of what district nursing work entails,
      and the implications there may be in emphasizing one aspect of care within a
      purchasing environment.

PMID- 9756216
TI  - An exploratory study of demand for the health visiting service within a marketing
      framework.
AB  - A small exploratory study was carried out to consider the concept of demand for
      the health visiting service from the clients' perspective. Because of the
      internal market introduced to the British health system under the National Health
      Service and Community Care Act, the idea of 'marketing' was used as a conceptual
      framework to underpin the study. Guided interviews were carried out with a sample
      of nine mothers of pre-school children to elicit the reasons why clients access
      the service, what they value about it and how they think it could be improved. A
      detailed qualitative analysis of these data indicates that demand for health
      visiting relates, in the first instance, to clients' knowledge of the service.
      This knowledge, and the extent to which the service meets their expectations,
      appear to influence the value the women place on health visiting and their
      subsequent use of it. A cycle is described, which illustrates critical points at
      which health visiting responses affect demand and use of service. The
      implications of the study for health visiting and for marketing the service are
      discussed.

PMID- 9756217
TI  - The distribution of community psychiatric nurses in England: are they where they
      should be?
AB  - Given the substantial increase in the numbers of community psychiatric nurses
      (CPNs) in England in the last 15 years this paper asks the question: is CPN
      activity where it should be? In-other words is activity distributed around the
      country according to need? Various indicators of need are suggested including
      population age structure, deprivation indices and suicide rates. We find no
      evidence -- based on information from scatterplots, Spearman correlations and
      more innovative measures of inequality -- that CPNs are distributed according to
      need. If this is confirmed by further research it is cause for alarm -- CPNs
      should be where they are most needed.

PMID- 9756218
TI  - The commissioning of nurse education by consortia in England: a quasi-market
      analysis.
AB  - The planning and commissioning of nurse education by consortia of NHS trusts and
      others in England is examined. These arrangements are analysed in terms of quasi
      market theory, investigating their ability to co-ordinate effectively the demand
      for nurse education and workforce demand for nurses. Hence the paper examines
      evidence concerning the success or failure of consortia to co-ordinate these
      aspects, discussing the arguments over nurse and student nurse shortages, and the
      procedure for assessing the demand for nurse training places. The paper argues
      that current nurse shortages illustrate past planning errors in commissioning
      nurse training. Consequently, the central body (National Health Service
      Executive) is still aiding consortia in their decision-making concerning numbers
      of nurse training places, modelling workforce plans and suggesting increases in
      training places (and producing the money to pay for this). As such, it is argued,
      the quasi-market is not as yet a completely devolved one. It is suggested in the
      concluding discussion that if qualitative benefits of consortia fail to
      materialize (as suggested elsewhere), and the quantitative functions are
      inadequate, the utility of consortia as planners and commissioners of nurse
      education may be questioned.

PMID- 9756219
TI  - The captive market in nurse education and the displacement of nursing knowledge.
AB  - This paper develops a framework of empowerment within which to examine the
      commissioning process for nurse education arising from market reform of the
      British National Health Service (NHS). The paper argues that an imbalance in this
      commissioning process favours theoretical products, such as the diploma-level
      nursing curricula (Project 2000). Also, the university setting of nurse education
      is seen as clinically de-skilling both nurse teachers and student nurses as well
      as influencing the discourses on clinical skills. The paper further argues that
      the effects of such trends are a captive market in nurse education contracting
      and a displacement of nursing knowledge. An approach to commissioning nurse
      education is described which may counter such trends and positively impact on NHS
      organizational development and quality. Further reform of the commissioning
      process is described in context of pragmatic health legislation.

PMID- 9756220
TI  - Evaluation of a course for charge nurses on caring for people with dementia.
AB  - The provision by nurses of appropriate levels of care for people with dementia is
      considered to be adversely affected by the inadequate provision of post basic
      education. This paper reports on a study that seeks to evaluate the effectiveness
      of a brief educational programme for charge nurses caring for people with
      dementia. In addition it focuses on behavioural change resulting from the course,
      for example, the degree of involvement of relatives in the care of their family
      member. The course is seen as a model for short courses for nurses working in
      this area. Qualitative methodology was utilized involving questionnaires and
      focused group interviews. The evaluation of the course incorporated pre- and post
      test design. The study identified factors that enhanced the charge nurses'
      educational experience. These factors included a course design incorporating
      andragogical teaching methods and the implementation of an action plan. The study
      also highlighted problems experienced by charge nurses in implementing an action
      plan. The action plan demonstrated that the type of involvement of relatives is
      more complex than presupposed and depended on such factors as the fear
      experienced by the relative of being left with the responsibility to care for
      their family member should they offer to contribute to their care in hospital.
      Recommendations for the design of future courses are made.

PMID- 9756221
TI  - Enrolled nurse conversion: trapped into training.
AB  - The introduction of Project 2000 in the late 1980s aimed to replace the existing
      two levels of nurse training with a single level of entry. This entailed phasing
      out training for enrolled nurses (ENs) and 'conversion' courses were introduced
      to allow ENs to upgrade their qualification. As part of a larger study of
      continuing education and training in the National Health Service (NHS), a cohort
      of ENs taking part in an open-learning conversion course were interviewed.
      Sixteen nurses described their motives for undertaking the course and the impact
      of the course on their work and home lives. Data collected in interviews were
      analysed using qualitative methods and revealed that all of these nurses felt
      under pressure to take part in the course. Participation in the course was
      associated with changes in home and work life. The findings of the study have
      implications in terms of study leave policy.

PMID- 9756222
TI  - Continuing care: developing a policy analysis for nursing.
AB  - Continuing care: developing a policy analysis for nursing Many authors have
      commented on the invisibility of nursing in policy development, implementation
      and analysis. Some of this invisibility may be attributed to the lack of an
      easily accessible framework to assist analysis of policy from a nursing
      perspective. In this paper we offer a framework for nursing policy analysis based
      on the domain concepts of nursing. We use continuing care for older people, a
      topical policy issue and fundamental nursing specialty, as a case study to
      demonstrate the utility and potential of such a framework in action. The
      resulting analysis helps identify areas of potential policy interest to nurses,
      raises questions for further policy analysis and offers a coherent position
      statement for action.

PMID- 9756223
TI  - Specialist practice: advancing the profession?
AB  - In 1994, the United Kingdom Central Council for Nursing, Midwifery and Health
      Visiting (UKCC) completed its framework for post-registration education and
      practice. The UKCC's strategy was based upon the two principles of compulsory re
      registration for all practising nurses and graduate-level (or equivalent) entry
      to specialist practice. It may be seen as the culmination of a gradual process of
      professionalization, as well as a response to changes in the organization and
      delivery of health care in the late 20th century. This paper uses both primary
      and secondary sources to trace the development of the new strategy, and its wider
      implications for the profession.

PMID- 9756224
TI  - Intervening to reduce anxiety for women with mild dyskaryosis: do we know what
      works and why?
AB  - In the United Kingdom women are encouraged to attend their general practice for
      cervical smear testing. Those who subsequently receive a mildly dyskaryotic
      result are placed under surveillance for 6 months before a further test is
      carried out. Receipt of a mildly abnormal result has been found to create anxiety
      in some women although it is suggested that this may be relieved by a
      specifically designed educational intervention. The qualitative investigation
      reported here explored the interaction which occurred during 10 nurse-patient
      consultations during which a practice nurse presented an educational intervention
      designed to relieve anxiety delivered as part of a randomized controlled trial.
      The investigation highlights factors relating to aspects of the intervention
      perceived by patients and nurses as successful and as unsuccessful. Implications
      for the management of women with mildly dyskaryotic results and for future nurse
      led educational interventions are proposed. The need for appropriate training for
      practice nurses is underlined. It is suggested that training should aim to assist
      the nurse to identify the patient's needs in order that interventions can be
      individually tailored and delivered effectively without creating anxiety with
      regard to other aspects of health.

PMID- 9756225
TI  - Women's lay knowledge of cervical cancer/cervical screening: accounting for non
      attendance at cervical screening clinics.
AB  - An assessment of women's knowledge of cervical screening and cervical cancer was
      considered important as up to 92% of those dying from this form of cancer had
      never been tested. What were the reasons which determined their non-attendance?
      Issues to be addressed were reactions to invitation, women's knowledge of
      screening, and the possible factors which they envisaged as being associated with
      cervical cancer. Other issues to be considered were practical problems associated
      with attendance, and preference for the sex and professional status of the health
      professionals involved; 187 women in a general practitioner practice in Lothian,
      Scotland were targeted by questionnaire. As with other studies in this field 50%
      of those contacted were ineligible for a variety of reasons. Seventy-two women
      completed the questionnaire, providing a mix of qualitative and quantitative
      data. Although the majority of women felt the invitation to attend screening was
      clear and easy to understand, there was a lack of knowledge with regard to both
      the screening itself and the possible causes of cervical cancer. The main
      'causes' were seen as higher sexual activity among those aged under 37 and
      smoking and a virus by those over 37. The majority of women showed preference for
      a female professional to take the smear. Practical problems of time and venue
      were not considered insurmountable. The main reasons cited for non-compliance
      were the fear and dislike of the test itself.

PMID- 9756226
TI  - Evidence-based care of Chinese men having transurethral resection of the prostate
      (TURP).
AB  - AIM OF STUDY: To measure the effect of specific preoperative information on
      postoperative anxiety, satisfaction with information, and demand for analgesia,
      of Chinese males having transurethral resection of the prostate (TURP). DESIGN: A
      controlled experimental design. The researchers allocated all patients (n = 30)
      undergoing TURP in a general hospital in Hong Kong, during a 3-month period, to
      one of two groups. The experimental group (n = 15) received a specific
      information pamphlet and a general preoperative counselling video. The control
      group (n = 15) received a video alone. PROCEDURE AND MEASURES: Following ethical
      approval, a researcher took baseline measures of state and trait anxiety using
      the Chinese State-Trait Anxiety Inventory (C -STAI). Five days after surgery the
      researcher administered the C-STAI (A-State), a patients' satisfaction
      questionnaire, and, recorded requests for analgesia during the first 5
      postoperative days. RESULTS: Experimental subjects reported significantly lower
      anxiety levels post-operatively and a significantly higher level of satisfaction
      with the preoperative information, than controls. Postoperative demand for
      analgesia did not significantly differ between groups. CONCLUSIONS: The findings
      support the importance of providing patients with specific, written preoperative
      information about their surgery and its effects to minimize their postoperative
      anxiety levels, and improve their satisfaction with the care provided.

PMID- 9756227
TI  - The role of the triage nurse practitioner in general medical practice: an
      analysis of the role.
AB  - A 2-year pilot study was undertaken in a group general practice to evaluate the
      nurse practitioner triage role. The study was undertaken in several stages which
      included a patient satisfaction questionnaire survey, follow-up interviews with
      30 patients from the questionnaire survey, and analysis of the nurse
      practitioner's work at different points over the 2-year study period. This paper
      describes the work of the nurse practitioner in comparison with that of seven
      general practitioners in a group general medical practice over a 5-day period in
      February 1996 and included patients' perceptions of their consultation. In this
      particular group medical practice, as in others throughout the country, many
      patients request same day appointments, often for self-limiting conditions,
      social advice and health education. This study demonstrates that the nurse
      practitioner can deal with such patients effectively and is undertaking an
      expanded and extended role in order to provide an holistic service to patients
      with which they are highly satisfied. It can be concluded that given the right
      kind of education and training and a supportive framework within the practice,
      the nurse practitioner undertaking a triage role can provide a highly effective
      service to patients and is a valuable member of the primary health care team.

PMID- 9756228
TI  - Are practice nurses an unexplored resource in the identification and management
      of alcohol misuse? Results from a study of practice nurses in England and Wales
      in 1995.
AB  - Changes in the health promotional work undertaken in primary care, including the
      work needed to meet the 'Health of the Nation' alcohol targets, have led to a
      rapid expansion of the number of practice nurses in England and Wales. However,
      there has been little evaluation of this role. This study provides data, for the
      first time at a national level, about practice nurses' work in identifying and
      managing patients drinking above recommended sensible guidelines. Data were
      collected by postal questionnaire from all nurses in a 50% random sample of 1852
      practices (drawn from a general practitioner (GP) national study, undertaken at
      the same time). 43% of nurses responded from 62% of the targeted practices.
      Respondents reported identifying a mean of 3.1 patients per month who were
      drinking above recommended sensible guidelines. These patients tended to be male,
      above 40 years of age and in contact with the nurse for the first time about this
      problem. Most patients were categorized as having a potential alcohol problem;
      few were classified as currently dependent. Very little intervention work was
      undertaken by nurses except for referral to the GP. If real progress is to be
      made in meeting the 'Health of the Nation' targets on population alcohol
      consumption, then primary care work in identifying alcohol misusing patients
      needs to be developed as a matter of urgency. The patients identified by practice
      nurses are those patients relevant to the 'Health of the Nation' alcohol targets.
      More emphasis needs to be placed on the valuable contribution practice nurses can
      make, particularly through the use of screening instruments and brief
      interventions.

PMID- 9756229
TI  - Promoting breast feeding: the perceptions of Vietnamese mothers in Sydney,
      Australia.
AB  - A review of the literature indicated that the majority of Vietnamese mothers
      bottle fed their infants after migration to western countries. Those who breast
      fed weaned their infants very early. This study aimed to explore, from the
      Vietnamese mothers' perspective, their experiences of infant feeding and the
      attributes of nurses, midwives, other health professionals and the health care
      system that were considered to be important in encouraging the immigrant
      Vietnamese women to breast feed in Sydney, Australia. A convenience sample of 124
      postnatal Vietnamese women were recruited from the western and southwestern
      suburbs of Sydney of New South Wales, Australia. In-depth interviews were
      conducted in the privacy of the respondents' homes. An ethnographic approach
      guided the concurrent data collection and content analysis. Through constant
      comparison of categories, nine concepts emerged from the findings to describe the
      women's process of decision making, experiences and perceptions of breast
      feeding: believing, complying, rewarding, facing the unexpected, experiencing
      pleasure and pain, fulfilling, communicating, counselling and supporting. These
      findings highlighted the significance of social, cultural and economic factors
      which influenced the women's decisions and maintenance of breast feeding.
      Implications for nursing practice and further research are discussed.

PMID- 9756230
TI  - Experiences and consequences of pain in persons with post-polio syndrome.
AB  - This study describes the meaning of pain and its implications for everyday life
      in 35 persons with symptoms of post-polio syndrome. The mean age of the study
      group is 65 years and the sex ratio of men to women is 1.5:1. The study persons
      were interviewed on two occasions in their homes and answered a pain
      questionnaire. The result shows that everyday vocabulary is used to express pain
      experiences. The study persons normally answered that it hurt, although the
      interviewers used pain in their questions. The results show that the lower back
      is the most common location of pain. Joint pains are most common in the upper
      extremities. The pain is worst in the evening and at night, and tangibly affects
      the daily rhythm. Physical strain and climatic factors commonly provoke pain,
      whereas rest and heat give relief. The study show that interviews and pain
      questionnaire should be supplemented with questions on activities so as to gain a
      comprehensive view of the difficulties experienced in everyday life.

PMID- 9756231
TI  - The discursive construction of dementia care: implications for mental health
      nursing.
AB  - This paper sets out a new approach to dementia that may be used to underpin
      mental health nursing practice. The paper begins by examining the development of
      community care. Various models of service provision to people with dementia are
      then critically examined. As an alternative to these approaches a new model of
      dementia is developed which highlights the position of various family members in
      the provision of dementia care including the person with dementia and also the
      importance of linguistic devices such as narrative and discourse. Finally the
      implications of this approach upon the mental health nursing practice are
      examined together with various suggestions for the development of research.

PMID- 9756232
TI  - Validation of the quality of life scale: living with HIV.
AB  - A grounded theory of Salvaging Quality of Life provided the conceptual framework
      for the development of the Living with HIV scale which was validated in this
      study. The HIV + convenience sample (n = 187) was 66% male, with a mean age of
      40.6 years, 69% African-American, and with an average CD4 count of 229 mm3. A
      principal components factor analysis with varimax rotation was conducted on the
      final 32-item scale and nine factors with Eigenvalues > 1 explained 60% of the
      variance. A second order factor analysis of these nine factors resulted in a two
      factor solution (HIV Struggles and HIV Reverence) which explained 49.4% of the
      variance. Cronbach alpha reliability coefficient for the total scale was 0.84.
      Differences between gender, ethnicity, education and presence of an AIDS
      diagnosis, and quality of life, were explored. Females had higher total scores
      which suggested they had a more positive quality of life than males. The Living
      with HIV scale can be used as a method of obtaining input from patients for care
      planning and for evaluating the effectiveness of nursing care intervention using
      quality of life as an outcome of care.

PMID- 9756233
TI  - Triangulation in nursing research: issues of conceptual clarity and purpose.
AB  - The controversy concerning the value of qualitative, quantitative and
      triangulation approaches to nursing research for understanding human behaviour
      and increasing nursing knowledge has been an increasing source of debate among
      nurse scholars. However, the differences and similarities of these three
      perspectives have not been fully compared as either philosophies or
      methodologies. The purposes of this paper are to provide an understanding of the
      origin and development of the triangulation research method, clarify major
      sources of confusion in the presentation of a triangulation study, and discuss
      the problems and possible solutions of a triangulation study. Finally, an example
      of multiple triangulation in a nursing research within a Taiwanese cultural
      context -- turning points of recovery from cardiac surgery during the intensive
      care unit transition -- is presented. In the course of the paper, suggestions are
      also given to help nurse researchers recognize when it is most appropriate to use
      a certain research method, whether that be qualitative, quantitative or
      triangulation.

PMID- 9756234
TI  - Staff views on the Resident Assessment Instrument, RAI/MDS, in nursing homes, and
      the use of the Cognitive Performance Scale, CPS, in different levels of care in
      Stockholm, Sweden.
AB  - Multidimensional functional assessment is the basis of individualized care. It is
      especially important in the care of elderly, with the complexity of
      symptomatology and often with cognitive impairment present. An assessment
      instrument for elderly persons, used in this study, is the Resident Assessment
      Instrument/Minimum Data Set (RAI/MDS) and its incorporated MDS Cognitive
      Performance Scale (CPS). The purposes of the study were to demonstrate the
      cognitive performance in elderly persons in different levels of care by using the
      CPS and to elicit the views of staff on use of the RAI/MDS. Cognitive impairment
      was found in 1276 elderly persons in six levels of care studied, an important
      factor to consider when organizing care of elderly. An intervention study was
      carried out for 1 year in three nursing home wards, with training and supervision
      in implementation of the RAI/MDS including individualized and documented care.
      Part of a questionnaire was used to evaluate staff (n = 50) views on using the
      instrument. A majority of the staff thought that the RAI/MDS could contribute to
      the improvement of quality of care, documentation in nursing records, and in co
      operation and engagement. Further research is necessary to elicit more knowledge
      on the usefulness and benefits of the instrument.

PMID- 9756235
TI  - An analysis of the effectiveness of focus groups as a method of qualitative data
      collection with Chinese populations in nursing research.
AB  - Although there has been a significant increase in the use of focus groups as a
      qualitative method of data collection in health and nursing research, literature
      on the use of this method with Chinese populations is limited. This study was
      therefore undertaken to explore the contribution of focus groups as a method of
      data collection amongst Hong Kong Chinese women. The study involved the
      comparison of the data obtained from two concurrent research studies which both
      employed case study design and focus groups as a major method of data collection.
      In both studies the samples involved Chinese women. The findings demonstrate that
      factors such as recruitment to the groups and interaction of group members did
      not adversely affect the quality of the data. Indeed the depth of data obtained
      on a range of sensitive topics suggests that the use of focus groups provides an
      effective method of collecting qualitative data with the Chinese populations in
      the described studies. However, a particular issue to emerge from this method of
      collection relates to the complexity of transcription and translation of the
      Chinese data which in the author's view has implications for the quality of the
      data. This finding indicates the importance of undertaking data analysis in the
      language of the interview, rather than that of the translated data, to avoid
      compromising the quality of data obtained from non-English speaking populations.

PMID- 9756236
TI  - Caring in nursing: a multivariate analysis.
AB  - The dimensions underlying the perceptions of caring among nurses were
      investigated using the Edinburgh Caring Dimensions Inventory (CDI). Exploratory
      and confirmatory factor analysis techniques were used. While there was a general
      caring factor on which the majority of the items in the CDI loaded, there were
      two separable major dimensions to caring, namely 'psychosocial aspects' and
      'professional and technical aspects'. In addition, two smaller dimensions were
      identified that were both related to self-giving, and it is postulated that these
      refer, respectively, to appropriate and inappropriate self-giving in nursing.

PMID- 9756237
TI  - The theory-practice gap in nursing: from research-based practice to practitioner
      based research.
AB  - The aim of nursing research is generally agreed to be the generation of
      knowledge, and whilst this is a relevant aim in theory-based disciplines such as
      sociology, the primary concern of nursing is with practice. Using examples drawn
      mainly from the field of mental health, it will be argued in this paper that the
      application of generalizable, research-based knowledge to individual, unique,
      person-centred practice, the so-called 'research-based practice' advocated by the
      Department of Health, is one of the main causes of the theory-practice gap. It
      will be further suggested that nursing requires a paradigm of clinical research
      which focuses on the individual therapeutic encounter in order to complement the
      existing sociological paradigm of theoretical research which is best suited to
      the generation of generalizable knowledge and theory. The paper will conclude by
      suggesting that such a clinically based research paradigm must not only focus on
      the individual nurse-patient relationship, but that it must be carried out by the
      nurse herself. Clinical research, if it is to make a difference to practice, must
      therefore be practitioner-based research.

PMID- 9756238
TI  - The leading edge. International Nursing Research Conference organized by the
      Royal College of Nursing of the United Kingdom Research Society at the James Watt
      Centre, Heriot Watt University, Edinburgh, Scotland, 3-5 April 1998.

PMID- 9756239
TI  - Estimates of the heights and weights of family members: accuracy of informant
      reports.
AB  - OBJECTIVE: Information about the accuracy of family informant estimates of height
      and weight should assist investigators in evaluating the costs and benefits of
      using this type of data in genetic study designs. DESIGN AND METHOD: To assess
      the accuracy of family informant estimates, 374 first-degree relatives from 94
      Caucasian families, gave estimates about the heights and weights of their first
      degree relatives. These estimates were compared with measured heights and weights
      to determine their accuracy. RESULTS: Informant estimates were highly predictive
      of measured heights (r=0.95), and weights (r=0.94), but informants systematically
      overestimated heights (mean=1.4 cm) and underestimated weights of their family
      members (mean=4.1 kg). CONCLUSIONS: On average, height estimates were generally
      within 1% of the measured height and weight estimates were within 3-5% of the
      measured weight. Therefore, these proxy measures can provide useful data, when
      measured or self-reported heights and weights are not available.

PMID- 9756240
TI  - Metabolic effects of biosynthetic growth hormone treatment in severely energy
      restricted obese women.
AB  - OBJECTIVE: Severe energy restriction in the treatment of obesity is limited by
      catabolism of body protein stores and, consequently, loss of lean as well as fat
      tissue. Growth hormone (GH), whose secretion is markedly impaired in obesity, is
      endowed with both lipolytic and protein anabolic properties. The aim of this
      study was to verify the effects of GH administration on body composition, plasma
      leptin levels and energy metabolism in obese patients undergoing severe dietary
      restriction. DESIGN: Single-blind placebo-controlled study. Twenty obese women
      were fed a diet of 41.86 kJ/kg ideal body weight (IBW) daily for 4 weeks: 10 of
      them were randomly assigned to a 4 week treatment with biosynthetic GH (rhGH,
      Saizen, Serono, Rome, Italy), 1 U/kg IBW/week in daily subcutaneous injections;
      the other 10 patients, matched for age and BMI, received vehicle only. SUBJECTS:
      Twenty women with simple obesity (age: 25.4+/-1.07 y, BMI: 35.9+/-0.35 kg/m2).
      MEASUREMENTS: Plasma IGF-I and leptin, serum markers of bone turnover (serum bone
      isoenzyme of alkaline phosphatase, osteocalcin and urinary hydroxyproline),
      nitrogen balance, body composition (by DEXA), and resting energy expenditure
      (REE, by indirect calorimetry) were evaluated at baseline and after 4 weeks.
      RESULTS: Mean IGF-I plasma levels, not influenced by energy restriction in
      patients receiving placebo, displayed a significant increase in the group treated
      with rhGH. The mean weight reduction and fat mass loss were not significantly
      different in the two groups (6.0+/-0.51 vs 7.2+/-0.30 kg, NS, and 5.36+/-0.460 vs
      4.28+/-0.572 kg, NS, with rhGH and placebo, respectively). Likewise, plasma
      leptin levels decreased significantly in weight-reduced subjects receiving either
      rhGH (from 16.2+/-2.37 to 6.4+/-0.39 ng/ml, P < 0.05) or placebo (from 14.3+/
      2.55 to 7.7+/-3.77 ng/ml, P < 0.05). On the contrary, the mean decrease of lean
      body mass (LBM) was significantly lower in the GH-treated patients than in those
      receiving vehicle (1.52+/-0.60 vs 3.79+/-0.45 kg, P < 0.05). In keeping with
      these findings, the mean daily nitrogen balance was significantly less negative
      in the GH-treated subjects than in the vehicle-injected patients (mean of the 4
      week daily urine collections -185.7+/-40.33 vs -363.9+/-55.47 mmol/d, P < 0.05,
      respectively). Further, a significant reduction of mean REE was recorded in the
      energy-restricted placebo-treated patients (from 8807+/-498 to 7580+/-321 kJ/24
      h, P < 0.05), but not in the patients receiving rhGH (from 8367+/-580 to 8903+/
      478 kJ/24 h, NS). Actually, when corrected for LBM, REE was even increased by GH
      administration (from 197.9+/-11.76 to 219.3+/-9.87 kJ/kg LBM/24 h, P < 0.05),
      whereas it was unchanged in the placebo group (from 201.7+/-13.85 to 190.0+/-9.87
      kJ/kg LBM/24 h, NS). A tendency of serum markers of bone turnover to increase was
      observed in the patients treated with rhGH, however with no changes in bone
      mineral content and density. CONCLUSION: rhGH treatment, though unable to enhance
      diet-induced weight and fat mass reduction, was effective in stimulating IGF-I
      production and conserving LBM and increasing its energy metabolism even in the
      presence of severe energy restriction.

PMID- 9756241
TI  - Weight-height relationships among eight populations of West African origin: the
      case against constant BMI standards.
AB  - OBJECTIVE: To ascertain whether constant body mass index (BMI) standards are
      appropriate in genetically similar populations. DESIGN: Data are taken from the
      International Collaborative Study of Hypertension in Blacks (ICSHIB), an
      observational study. SUBJECTS: Individuals of African descent who were included
      in ICSHIB. Subjects lived in eight different sites: Barbados; Cameroon (urban and
      rural); Jamaica; Manchester, UK; Maywood, IL; urban Nigeria; and St Lucia.
      MEASUREMENTS: Weight and height. RESULTS: Constant BMI standards effectively
      argue for the constancy of slope of the linear regression equations of In(weight)
      on In(height) across populations. Linear regression results indicate that the
      height/weight relationship implied by the use of constant BMI standards, is not
      found in these populations and that there is much variation across groups.
      CONCLUSION: The use of constant BMI standards in classifying individuals
      prognostically may be unwise, even in genetically similar populations.

PMID- 9756242
TI  - The effect of six months training on weight, body fatness and serum lipids in
      apparently healthy elderly Dutch men and women.
AB  - OBJECTIVE: To investigate the effect of a six-months training program on changes
      in body weight and lipid concentrations, and their interrelationship in elderly
      people. DESIGN: Intervention study. The elderly subjects were randomly assigned
      to a control group or one of two supervised aerobic training groups, either all
      round activities or ergometer cycling, both exercising 3-4 times a week for six
      months. SUBJECTS: 229 elderly men and women, aged 60-80 y. MEASUREMENTS: Various
      fatness parameters by anthropometry, serum lipids and peak power output. RESULTS:
      During the intervention, no significant changes were observed in weight or body
      fatness in subjects of the training groups. Serum high density lipoprotein (HDL),
      low density lipoprotein (LDL) and total cholesterol and triglycerides tended to
      change in a favourable direction in the elderly of the intervention groups, but
      only triglyceride concentration in women of the cycle ergometer group (mean
      difference with controls: -0.24 mmol/L, 95% confidence interval (CI): -0.45, 
      0.03) and total serum cholesterol and HDL-cholesterol concentrations in subjects
      of the all-round activity group, (-0.32mmol/L, 95% CI: -0.63, -0.01 and 
      0.15mmol/L, 95% CI -0.25, -0.05, respectively) were significantly reduced as
      compared to controls. Regression analysis showed that the intervention-control
      difference in change of all lipids was independent of changes in weight, body fat
      and previous engagement in sport activity. CONCLUSION: Regular physical exercise
      in an elderly population resulted in favourable changes in serum lipid
      concentrations that were not significant, but no change in body weight or
      fatness. Change in lipid concentration could not be attributed to change in
      weight or body fat.

PMID- 9756243
TI  - Agreement of skinfold measurement and bioelectrical impedance analysis (BIA)
      methods with dual energy X-ray absorptiometry (DEXA) in estimating total body fat
      in Anglo-Celtic Australians.
AB  - OBJECTIVE: To compare percentage total body fat (%BF) estimated by the four
      skinfold thickness measurement (SKF) and single-frequency bioelectrical impedance
      analysis (BIA) methods using three different sets of equations, to that assessed
      by the dual energy X-ray absorptiometric (DEXA) method using a Lunar DPX
      densitometer. DESIGN: Cross-sectional study. SUBJECTS: An Anglo-Celtic Australian
      population of 66 males and 130 females (age: 26-86 y). MEASUREMENTS: %BF by
      anthropometry, BIA using three different sets of equations and DEXA. RESULTS:
      Mean %BF assessed by DEXA (%BF(DEXA)) was similar to that estimated by SKF
      (%BF(SKF)) in males, while %BF(DEXA) was slightly higher in females. %BF
      estimated by BIA (%BF(BIA)) was significantly lower than %BF(DEXA) in females,
      regardless of equations used for calculation, while the level of agreement
      between BIA and DEXA in estimating %BF in males was dependent on prediction
      equations used for calculation of %BF(BIA). A better agreement was obtained from
      the use on the prediction equations of Segal et al (1988), compared to other two
      sets of equations. The agreement between SKF or BIA and DEXA declined with
      increasing %BF. CONCLUSIONS: There was a good agreement between DEXA and SKF, and
      slightly less so between DEXA and BIA, in estimating %BF in an Anglo-Celtic adult
      population. The agreement in most cases, however, was dependent on the degree of
      body fatness. In comparison to DEXA, both SKF and BIA, with the use of the
      equations of Segal et al (1988), are applicable to estimate %BF in an Anglo
      Celtic Australian population.

PMID- 9756244
TI  - Coping, personality and the development of a central pattern of body fat from
      youth into young adulthood: The Amsterdam Growth and Health Study.
AB  - OBJECTIVE: It has been suggested that coping behaviour, in particular a defeat
      reaction to stress, is a determinant of the central pattern of body fat. To
      verify this hypothesis, this study investigated if coping behaviour, and
      associated personality traits, are associated with a central pattern of body fat
      or total body fatness in a healthy population of males (n=83) and females (n=98)
      early in life. METHODS: Problem-focused, emotion-focused and type A behaviour
      were measured at the mean ages of 21 y and 27 y. Personality traits (inadequacy,
      social inadequacy, dominance, rigidity and debilitating anxiety), a central
      pattern of body fat (subscapular/triceps, (S/T) ratio) and total body fatness
      (sum of four skinfolds (SSF): biceps, triceps, subscapular, suprailiac) were
      measured six times between the ages of 13-27 y. RESULTS: In both genders, no
      association was found between either coping strategy and a central pattern of
      body fat or total body fatness. In males, type A behaviour was significantly
      negatively correlated with the S/T ratio (r = -0.27, P=0.01) after adjustment for
      total body fatness, at the mean age of 27 y. In a longitudinal analysis, adjusted
      for total body fatness, dominance and rigidity were negatively associated with
      the S/T ratio (beta = -0.09, 95% confidence interval (95% CI) (-0.17; -0.00) and
      beta = -0.11, 95% CI (-.19; -0.02), respectively) between the ages of 13-21 y in
      males. These associations of type A behaviour, dominance and rigidity, with a
      central pattern of body fat, were weaker and did not reach statistical
      significance with total body fatness. CONCLUSIONS: The results of this study
      justify further research on the association between coping behaviour, personality
      and the development of a central pattern of body fat.

PMID- 9756246
TI  - Gender differences in fat mass of 5-7-year old children.
AB  - OBJECTIVE: Studying gender differences in fat mass and distribution in a
      homogeneous group of children. DESIGN: Cross-sectional study. SUBJECTS: 610
      children aged 5-7 y in Kiel, Germany. METHODS: Anthropometric measures,
      bioelectrical impedance analysis (BIA). RESULTS: Although boys had increased body
      weights (P<0.05), body mass indexes (BMI's) (P<0.001) and waist/hip ratios (WHRs)
      (P<0.001), the %fat mass as assessed by BIA (P<0.05) was increased in girls.
      Although the increased BMI in boys was independent of the percentile used, gender
      differences (that is, lower values for boys than for girls at the same age) in
      WHR, the sum of four skinfolds and %fat were seen up to the 90th percentile. By
      contrast, above the 90th percentile there were no differences in skinfold
      thickness and %fat between boys and girls. Studying 42 BMI-matched pairs (boys
      and girls) also showed that the %fat estimated by BIA (P<0.001) was increased in
      girls. Plotting the average of %fat as obtained from skinfold- and BAI
      measurements against the difference between data obtained by the use of the two
      methods shows that BIA %fat overestimates skinfold %fat at low or normal percent
      fat mass (that is, up to 20%) in both genders. By contrast, at increased fat
      mass, BIA %fat seems to underestimate skinfold %fat in both genders. CONCLUSIONS:
      Gender differences in fat mass and fat distribution are obvious in children aged
      5-7 y. These differences are independent of gender differences in body weight.
      However, the nutritional state has an influence and gender differences cannot be
      detected in overweight and obese children. Our data also suggest that a children
      specific formula used to calculate %fat from skinfold measurements is
      inappropriate.

PMID- 9756245
TI  - Substrate oxidation and thyroid hormone response to the introduction of a high
      fat diet in formerly obese women.
AB  - OBJECTIVE: To investigate the adaptation in substrate utilization to a sudden
      change in dietary composition from a medium fat to a high fat diet, during a
      three day period in formerly obese and never obese women. METHODS: Energy
      expenditure (EE) and substrate oxidation rates were measured in eight healthy
      formerly obese women and eight never obese controls, during four consecutive days
      in a respiration chamber. The first day and the day prior to the experiment, the
      subjects consumed a diet with 30 energy-% fat, whereas the diet had 55 energy-%
      fat on the subsequent three days. RESULTS: The rate of adjustment of oxidative
      substrate partitioning expressed as 24 h non-protein respiratory quotient (RQnp)
      was similar in the two groups. RQnp on each of the days was also similar between
      the two groups, after accounting for a group difference in energy balance, caused
      by a non-significantly lower EE in the formerly obese women. However, the
      formerly obese subjects, demonstrated a greater suppression of postprandial fat
      oxidation after supper, which was unrelated to energy balance. Furthermore, the
      formerly obese subjects, in contrast to the controls, exhibited a reduction in
      plasma triiodothyronine/thyroxine ratio (T3/T4) following the high fat diet. A
      positive correlation between T3/T4 and EE was found in the 16 subjects.
      CONCLUSIONS: The formerly obese subjects did not show a slower adaptation rate of
      substrate utilization when challenged with a high fat diet, but exhibited an
      enhanced suppression of fat oxidation and a lower T3/T4 ratio after supper, when
      fed a high fat diet.

PMID- 9756247
TI  - Covert manipulation of energy density of high carbohydrate diets in 'pseudo free
      living' humans.
AB  - OBJECTIVE: This study examined the effects of varying the energy density (ED) of
      high carbohydrate (HC) diets on food and energy intake (EI), subjective hunger
      and body weight in humans. DESIGN: Randomised cross-over design. Subjects were
      each studied twice during 14 d, throughout which they had ad libitum access to
      one of two covertly-manipulated diets. SUBJECTS AND METHODS: Six healthy men
      (mean age (s.d.)=32.17 y s.d. (5.26 y), mean weight=69.74 kg s.d. (2.75 kg), mean
      height=1.76 m s.d. (0.05 m), body mass index (BMI)=22.57 (2.2) kg/m2) were
      studied. The fat, carbohydrate (CHO) and protein content (as % energy) and ED of
      each diet were 21:66:13% and 357 kJ/100 g, (low-energy density (LED)) or
      22:66:12% and 629 kJ/100 g (high-energy density (HED)). A medium fat diet was
      provided at maintenance (1.6 x BMR, MF for 2 d) before each ad libitum period.
      Subjects could alter the amount, but not the composition of foods eaten. RESULTS:
      Mean EI was 8.67 and 14.82 MJ/d on the LED and HED diets, respectively. Subjects
      felt significantly more hungry on the LED diet, than on the HED diet
      (F(1,160)38.28; P < 0.001) and found the diets to be similarly pleasant (72.72 mm
      vs 71.54 mm (F(1,392)0.31; P = 0.579)). Mean body weight decreased on the LED
      diet at a rate of 0.1 kg/d and increased at 0.06 kg/d on the HED diet
      (F(1,131)86.60; P < 0.001), giving total weight changes of -1.41 kg and +0.84 kg,
      respectively, both of which were significantly different from zero (P < 0.01).
      CONCLUSION: Excess EI is possible on HC, HED diets, at least under conditions
      where diet selection is precluded. Comparison of these results with previous
      studies, which altered ED using fat, suggests that CHO may be a better cue for
      hunger than fat.

PMID- 9756248
TI  - The metabolic effects of preferential reduction of visceral adipose tissue in
      abdominally obese men.
AB  - SETTING: This study was performed on free living subjects attending the body
      composition laboratory on a monthly basis for a total of six months.
      SUBJECTS/DESIGN: Thirty-one abdominally obese men (30 <body mass index (BMI) <40,
      waist-to-hip ratio (WHR)>0.95) were enrolled in a placebo-controlled randomized
      double-blind study, using either dexfenfluramine (d-fen) or placebo, whilst also
      receiving food and fitness counselling. After a two week run-in period they were
      randomized to either d-fen or placebo for three months. This was followed by a
      further three months without medication, although food and fitness counselling
      continued. METHODS: Body composition assessment included anthropometry (weight,
      height and abdominal circumferences), dual-energy X-ray absorptiometry (DEXA) for
      total body fat, and intra-abdominal fat measured via magnetic resonance imaging
      (MRI) at the L3/L4 level. Biochemistry included serum lipids, insulin and
      glucose. All measurements including blood pressure were performed at baseline,
      three months and six months. STATISTICAL ANALYSIS: The change within each group
      in the three months on medication (d-fen or placebo) was assessed by paired t
      tests, whilst the difference between the groups at baseline and at three months
      (measured by percentage change from baseline) was assessed by unpaired t-tests.
      An analysis of variance was performed over the six months for the d-fen group and
      the placebo group separately, to determine the overall effect of three months
      treatment with either d-fen or placebo, three months after medication had ceased.
      OUTCOMES AT THREE MONTHS: At three months, BMI decreased by -5.8+/-0.8% in the
      group on d-fen and by -2.7+/-0.8% in the placebo group (P<0.01 d-fen vs placebo).
      There was also a significant difference in the reduction of the visceral fat area
      between the groups (-21.0+/-4.0% in the d- fen group vs -6.7+/-2.2% in the
      placebo group, P<0.01) although there was no significant difference between
      groups with regard to reduction in subcutaneous fat area. The
      visceral:subcutaneous fat ratio (V/S ratio) was significantly reduced between
      groups at three months (-13.3+/-4.9% in the d-fen group vs -0.7+/-3.0% in the
      placebo group, P=0.03). At three months, the only metabolic parameters to show
      significant difference between the two groups were total cholesterol and LDL
      cholesterol. Total cholesterol reduced by -12.4+/-2.0% in the d-fen group
      compared with -2.3+/-2.1% in the placebo group (P<0.01). LDL cholesterol reduced
      by -15.6+/-2.6% in the d-fen group compared with -1.2+/-2.8% in the placebo group
      (P<0.01). OUTCOMES AT SIX MONTHS: In the d-fen group, the reductions in BMI,
      abdominal circumference and % total body fat (DEXA) were sustained after three
      months on no medication, whereas all changes in body composition seen in the
      group on placebo at three months, had reverted at the three month follow-up. Both
      groups sustained a reduction in the insulin to glucose (I/G) ratio and systolic
      and diastolic blood pressure for three months after medication was ceased, while
      those on d-fen initially also maintained a reduction in total and LDL
      cholesterol.

PMID- 9756249
TI  - Leptin concentrations are associated with higher proinsulin and insulin
      concentrations but a lower proinsulin/insulin ratio in non-diabetic subjects.
AB  - INTRODUCTION: Leptin (the product of the human OB gene) is increased in obese
      individuals, suggesting resistance to its effect. However, there is considerable
      variability in leptin levels at each level of body mass index (BMI), suggesting
      that genetic and environmental factors may regulate leptin concentrations.
      Previous data have suggested that leptin levels are associated with insulin
      resistance and in a few reports with impaired insulin secretion. We examined
      whether non-diabetic subjects, with elevated specific insulin and proinsulin
      levels, had increased leptin levels. METHODS: We used a radioimmunoassay (RIA) to
      measure serum leptin levels in 197 non-diabetic Mexican Americans and non
      Hispanic whites from the San Antonio Heart Study. We also evaluated whether
      leptin levels were associated with impaired insulin secretion or increased beta
      cell stress, as evaluated by the fasting proinsulin/insulin ratio. (Higher
      fasting proinsulin/insulin ratios are thought to reflect impaired insulin
      secretion.) RESULTS: Leptin levels were significantly correlated with fasting
      specific insulin (r=0.55, P<0.001) and proinsulin (r=0.57, P<0.001) and inversely
      with the proinsulin/insulin ratio (r= -0.154, P=0.035) after adjustment for age,
      gender, ethnicity and 2 h glucose. These associations were similar in men and
      women and in Mexican Americans and in non-Hispanic whites. After further
      adjustment for BMI and waist-to-hip ratio (WHR), leptin levels remained
      significantly correlated with specific insulin (r=0.31, P<0.001) and proinsulin
      (r=0.24, P<0.001) although the magnitude of the associations were considerably
      attenuated. CONCLUSION: We conclude that specific insulin and proinsulin are
      positively related to leptin levels and that these associations are to some
      degree independent of obesity and body fat distribution. Thus, subjects with
      increased insulin levels may be relatively resistant to the effects of leptin.
      However, leptin levels are associated with a decrease in the fasting
      proinsulin/insulin ratio suggesting that leptin levels are not associated with an
      impairment in insulin secretion.

PMID- 9756250
TI  - Effect of hydrolyzed guar fiber on fasting and postprandial satiety and satiety
      hormones: a double-blind, placebo-controlled trial during controlled weight loss.
AB  - OBJECTIVE: To evaluate the effects of a completely soluble fiber on fasting and
      postprandial hormone levels, respiratory quotient (RQ) and subjective ratings of
      satiety during a controlled weight-loss program. DESIGN: In a five-week
      prospective, randomized, double-blind study, a 3.3 MJ (800 kcal)/d diet was
      provided during a two-week wash-in period. Then, during the intervention weeks,
      separated by a one-week wash-out period, a 3.3 MJ (800 kcal) formula containing
      either 20 g fiber or placebo daily, was given in a cross-over design and on days
      1, 3 and 7 of the intervention weeks (weeks 3 and 5) measurements were taken
      after an overnight fast. SUBJECTS: 25 obese but otherwise healthy females (age:
      46+/-6 y, body mass index (BMI): 35+/-6 kg/m2) were studied. MEASUREMENTS: Body
      weight; hunger/satiety ratings; glucose, insulin, cholecystokinin (CCK) and
      leptin concentrations; RQ during the intervention weeks. RESULTS: In the fasting
      state, the supplement had no effect on any of the measured parameters, including
      blood concentrations of glucose, insulin, CCK, and leptin, RQ and satiety
      ratings. In the 2 h postprandial period following the test meal, none of the
      measured parameters differed significantly from that following the non-fiber
      supplemented meal, except for the CCK response. CCK demonstrated an overall
      higher concentration after the fiber-supplemented meal (P=0.007), even after
      adjustment for age, weight, height and treatment sequence. The postprandial peak
      in CCK also occurred earlier (at 15 min vs 30 min) after completion of the fiber
      supplemented meal. CONCLUSIONS: The results indicated that a hydrolyzed guar gum
      fiber supplement produced a heightened postprandial CCK response, but did not
      alter other satiety hormones or increase satiety ratings, in either the fasting
      or the postprandial state.

PMID- 9756251
TI  - Insulin sensitivity in obese normotensive adults: influence of family history of
      hypertension.
AB  - OBJECTIVE: To evaluate the influence of family history of hypertension on insulin
      sensitivity in obese normotensive adults, comparing them with lean subjects.
      SUBJECTS: 136 normotensives (N)(mean 24 h blood pressure < 130/80 mmHg; age range
      35-45 y): 32 lean (body mass index, BMI < or = 25 kg/m2) N with normotensive
      parents (F-), 37 lean N with one or two parents hypertensive (F+), 32 obese (BMI
      > or = 30 kg/m2) NF- and, 35 obese NF+. METHODS: 24 h ambulatory blood pressure
      monitoring; glucose, insulin and C-peptide before and 30, 60, 90 and 120 min
      after an oral glucose load; index of insulin peripheral activity (Ia:
      10(4)/insulin x glucose values at glucose peak); fasting insulin/C-peptide ratio
      (I/Cp). RESULTS: The four groups were comparable for age, gender and blood
      pressure values throughout the 24 h. Glucose, fasting and during test, and I/Cp
      were similar among the four groups; insulin and C-peptide, fasting and
      stimulated, were significantly higher and Ia lower in obese N than in lean N; at
      similar BMI, insulin and C-peptide were significantly higher and Ia lower, in F+
      than in F-. The correlation between insulin and BMI was significantly closer in F
      than in F+. CONCLUSIONS: Family history of hypertension appears to be
      significantly associated with insulin sensitivity in both lean and obese
      normotensive adults; moreover, overweight and a genetic predisposition to
      hypertension may have additive adverse effects on insulin sensitivity in
      normotensive adult subjects.

PMID- 9756252
TI  - Body fatness: longitudinal relationship of body mass index and the sum of
      skinfolds with other risk factors for coronary heart disease.
AB  - OBJECTIVE: To analyse the longitudinal relationships between body mass index
      (BMI)/sum of skinfolds (SSF) and biological and lifestyle risk factors for
      coronary heart disease (CHD). DESIGN: An observational longitudinal study; that
      is, the Amsterdam Growth and Health Study. SUBJECTS: 181 males and females,
      initially aged 13 y. Over a period of 15 y, six repeated measurements were
      carried out. MEASUREMENTS: BMI and SSF, biological CHD risk factors; that is,
      total cholesterol (TC), high density lipoprotein (HDL), TC:HDL ratio,
      systolic/diastolic blood pressure (SBP/DBP) and cardiopulmonary fitness (VO2-max)
      and lifestyle CHD risk factors (that is, daily physical activity, dietary
      parameters, smoking, and alcohol consumption). The longitudinal relationships
      were analysed by an autoregressive model, in which the value of the outcome
      variable at time-point t is not only related to the value of the predictor
      variable at t, but also to the value of the outcome variable at t-1. RESULTS:
      Both BMI and SSF were positively related to TC and the TC:HDL ratio. Only BMI was
      positively related to SBP and only SSF was negatively related to VO2-max.
      Physical activity was negatively related to SSF. None of the other lifestyle
      parameters were related to SSF and/or BMI. CONCLUSIONS: Both BMI and SSF were
      related to a high risk profile regarding CHD. Different relationships for SSF and
      BMI are found, because BMI not only reflects body fatness, but also lean body
      mass. Analyses with BMI as an indicator for body fatness should therefore be
      interpreted cautiously.

PMID- 9756253
TI  - Stimulation by leptin of 3H GDP binding to brown adipose tissue of fasted but not
      fed rats.
AB  - OBJECTIVES: To assess the effects of intracerebroventricular (i.c.v.) leptin
      administration on rats fed ad libitum or fasted on 3H GDP binding to brown
      adipose tissue (BAT). SUBJECTS: Groups of 5-6 ten-week-old male Wistar rats.
      EXPERIMENTAL DESIGN: An i.c.v. cannula was inserted and unilateral denervation of
      interscapular brown adipose tissue (BAT) was performed 5 d before each study.
      Thereafter, leptin was infused i.c.v. during 72 h while rats were fed ad libitum
      or fasted. Vehicle-infused, pair-fed or fasted rats were used as controls.
      MEASUREMENTS: 3H GDP binding to innervated and denervated BAT mitochondria.
      RESULTS: 3H GDP binding to innervated or denervated BAT of rats fed ab libitum
      compared to vehicle-infused, pair-fed rats was not increased by i.c.v. leptin. 3H
      GDP binding was lower in fasted than in fed rats, and the difference was larger
      in innervated than denervated BAT. I.c.v. leptin increased 3H GDP binding by 30%
      in innervated, and by 51% in denervated BAT (P < 0.05) in fasted rats.
      CONCLUSIONS: I.c.v. leptin does not increase 3H GDP binding to BAT of rats fed ad
      libitum compared to pair-fed (food-restricted) rats. In contrast, i.c.v. leptin
      produces a mild stimulation of 3H GDP binding to BAT of fasted rats. This effect
      is not mediated by the sympathetic nervous system, because it is observed in both
      innervated and denervated BAT. These results are compatible with the concept
      that, in fasting rats, the decrease in leptin secretion contributes to the
      reduction in 3H GDP binding to BAT mitochondria.

PMID- 9756254
TI  - Hormonal status and NIDDM in the European and Melanesian populations of New
      Caledonia: a case-control study. The CALedonia DIAbetes Mellitus (CALDIA) Study
      Group.
AB  - OBJECTIVE: To assess ethnic differences in androgenic status related to non
      insulin-dependent diabetes mellitus (NIDDM) in male and female Melanesians and
      Europeans of New Caledonia. DESIGN: This is a case-control study nested in a
      prevalence study for diabetes mellitus in the multiracial population of New
      Caledonia. SUBJECTS: 186 male subjects were included in the survey (77
      Melanesians and 16 Europeans in each case and control group). Each case and
      control group included 104 female Melanesian subjects (69 premenopausal and 35
      postmenopausal). METHODS: Diabetic subjects were matched for age, gender, ethnic
      group and location, with healthy normoglycaemic subjects. Testosterone levels in
      men and sex hormone-binding globulin (SHBG) levels in women (measured by
      radioimmunoassay, RIA) were compared between NIDDM and control subjects in
      relation to obesity, central adiposity and insulin levels. RESULTS: In both
      ethnic groups, NIDDM was associated with lower testosterone levels but there was
      a marked difference among Europeans. Testosterone was negatively associated with
      the body mass index (BMI) (r= -0.35, P <0.01) and fasting insulin (r= -0.37, P
      <0.001) in control Melanesians only. In Melanesian women, NIDDM was associated
      with lower SHBG levels in pre- and postmenopausal women (P <0.001). SHBG mean
      level was not associated with menopausal status. CONCLUSION: Our results confirm
      in a Pacific population that NIDDM is associated with low levels of testosterone
      in men and low levels in SHBG in women. In contrast to white populations,
      Melanesian women have a more androgenic profile, whatever their menopausal
      status.

PMID- 9756255
TI  - Renal size and composition in hypertensive, obese rabbits.
AB  - OBJECTIVE: To determine whether the renal growth associated with obesity is due
      to hypertrophy or hyperplasia. DESIGN: New Zealand white female rabbits were fed
      either standard rabbit chow (n=17) or chow fortified with 10% corn oil plus 5%
      lard (n=18) for 12-16 weeks. MEASUREMENTS: All rabbits were weighed, and intra
      arterial blood pressures were successfully measured at the end of the study in 16
      lean and 18 obese rabbits; percent water of entire kidneys (8 lean, 8 obese
      rabbits) and of defined regions of kidneys (8 lean, 10 obese rabbits) were
      obtained gravimetrically. Renal hemoglobin, protein and DNA was measured
      chemically (8 lean, 8 obese rabbits). RESULTS: Kidneys grew in size as the
      rabbits gained fat. In a series of 8 lean and 8 age-matched obese rabbits,
      weighing 3.7+/-0.1 kg and 5.4+/-0.4kg (P<0.05), the kidneys were 20% larger in
      the obese rabbits: 15.0+/-0.9 g vs 18.0+/-2.5 g (P<0.05). Kidney protein was also
      20% greater in the obese rabbit: 1.38+/-0.06 g/kidney vs 1.66+/-0.06 g/kidney
      (P<0.05). While total renal DNA was 16% greater in the obese: 18.2+/-0.5
      microg/kidney vs 21.1+/-0.61 g/kidney (P<0.05), no significant difference existed
      when the DNA was expressed as microg/mg protein. Fractional water content of the
      intact kidney declined with obesity: 78.7+/-1.1% vs 76.0+/-1.2% (P<0.05).
      Conversely, the hemoglobin content of the kidney at autopsy, an estimate of the
      unstressed vascular volume, increased with obesity: 55+/-19 mg/kidney vs 82+/-25
      mg/kidney (P<0.05). By contrast, water content of renal parenchyma was constant:
      80.8+/-1.0% vs 80.9+/-1.2% (cortex); 84.0+/-0.8% vs 83.6%+/-2.0% (outer medulla);
      and 85.7+/-0.8% vs 86.0+/-2.1% (inner medulla). CONCLUSION: The renal growth
      associated with obesity was predominantly hyperplastic and was associated with a
      partial exclusion of fluid from the renal sinus.

PMID- 9756256
TI  - Analysis of the uncoupling protein-1 (UCP1) gene in obese and lean subjects:
      identification of four amino acid variants.
AB  - Uncoupling protein-1 (UCP1) is uniquely expressed in brown adipose tissue (BAT)
      and of major importance for the tissues thermogenic capacity. This study was
      undertaken to detect variants in the UCP1 gene by single strand conformational
      polymorphism (SSCP) analysis and subsequent sequencing, and determine their
      potential association with obesity. Four variants predicting for amino acid
      substitutions were detected, of which Arg40Trp (exon 1) and Lys257Arg (exon 5)
      were rare mutations. In contrast, the allele frequency of a polymorphism in exon
      2 predicting for an Ala64Thr substitution was 8.2% in a cohort of 293 obese
      children and adolescents compared to 4.1% in 134 lean individuals, while the
      allele frequency of a Met229Leu variant (exon 5) was not markedly different
      between the obese (10.4%) and lean (12.0%) study groups. Although one of the
      identified polymorphisms tends to have a higher frequency in obese than in lean
      subjects, variants of the UCP1 gene do not seem to contribute significantly to
      the development of early-onset obesity in the German population.

PMID- 9756257
TI  - Individual effects on biomechanical variables during landing in tennis shoes with
      varying midsole density.
AB  - The aim of this study was to determine whether individuals responded uniquely to
      three different pairs of tennis shoes that differed only in midsole hardness.
      Kinematic and kinetic data were collected while the subjects (n = 3) performed a
      stereotyped lateral movement wearing each of the three pairs of tennis shoes. The
      results were analysed statistically for each subject separately. Variables were
      identified as discriminators between shoes for individual subjects based upon the
      results of separate discriminant analyses. After these analyses, a multivariate
      analysis of variance (MANOVA) was used for each subject to determine whether the
      discriminator variables differed significantly between shoes. A scoring system
      was devised that used the results of the MANOVA to assign scores to shoes for
      each variable. Cumulative scores for shoes (for each subject) were compared to
      determine which shoe was best for a subject. The results indicated that each
      subject responded uniquely to the shoes, and each demonstrated a preference for a
      particular pair of shoes. A need for single-subject designs exists when
      evaluating variations in athletic shoes.

PMID- 9756258
TI  - Anthropometric-based selection and sprint kayak training in children.
AB  - A 12 week kayak training programme was evaluated in children who either had or
      did not have the anthropometric characteristics identified as being unique to
      senior elite sprint kayakers. Altogether, 234 male and female school children
      were screened to select 10 children with and 10 children without the identified
      key anthropometric characteristics. Before and after training, the children
      completed an all-out 2 min kayak ergometer simulation test; measures of oxygen
      consumption, plasma lactate and total work accomplished were recorded. In
      addition, a 500 m time trial was performed at weeks 3 and 12. The coaches were
      unaware which 20 children possessed those anthropometric characteristics deemed
      to favour development of kayak ability. All children improved in both the 2 min
      ergometer simulation test and 500 m time trial. However, boys who were selected
      according to favourable anthropometric characteristics showed greater improvement
      than those without such characteristics in the 2 min ergometer test only. In
      summary, in a small group of children selected according to anthropometric data
      unique to elite adult kayakers, 12 weeks of intensive kayak training did not
      influence the rate of improvement of on-water sprint kayak performance.

PMID- 9756259
TI  - Comparisons of the ski turn techniques of experienced and intermediate skiers.
AB  - We compared selected kinematic variables for four different ski turn techniques
      performed by five experienced and five intermediate male skiers. The four ski
      turn techniques were the upstem turn, the downstem turn, the parallel turn and
      the parallel step turn. Each turn was divided into the initiation phase and the
      first and second steering phases. Most of the statistically significant
      differences (P < 0.05) between the two groups were found for the initiation
      phases of the four turns. Both the hip axis-hand axis angle and the edging angle
      of the uphill ski were significantly different between the two groups for the
      upstem turn at the beginning of the initiation phase. For the downstem turn,
      significant differences between the groups were found at the start of the
      initiation phase for the hip axis-hand axis angle, the shoulder axis-fall line
      angle, and the edging angle of the uphill ski. The standard deviation of the
      distance between the tips of the two skis over the second steering phase also
      differed significantly between the two groups. For the parallel step turn,
      significant differences were found at the start of the initiation phase for the
      edging angle of the downhill ski and the downhill ski to movement direction
      angle. Significant differences were also found for the edging angle of the
      downhill ski in the middle of the second steering phase and the shoulder axis to
      movement direction angle at the end of this phase. For the initiation phase of
      the parallel turn, significant differences were found for the timing of setting
      the ski pole, the uphill knee angle at the start of this phase and the range of
      the knee angle of the uphill leg from the start to the end of this phase. For
      this turn, significant differences between the two groups were also found for the
      edging angle of the downhill ski in the middle of the second steering phase and
      the shoulder axis to movement direction angle at the end of this phase. One of
      the reasons it was possible to identify a few significant differences only for
      the turns analysed, was the variability within the intermediate group: for most
      of the variables analysed, the standard deviation was much higher for the
      intermediate than for the experienced group.

PMID- 9756260
TI  - Heart rate, blood lactate and kinematic data of elite colts (under-19) rugby
      union players during competition.
AB  - Physiological and kinematic data were collected from elite under-19 rugby union
      players to provide a greater understanding of the physical demands of rugby
      union. Heart rate, blood lactate and time-motion analysis data were collected
      from 24 players (mean +/- s(x): body mass 88.7 +/- 9.9 kg, height 185 +/- 7 cm,
      age 18.4 +/- 0.5 years) during six competitive premiership fixtures. Six players
      were chosen at random from each of four groups: props and locks, back row
      forwards, inside backs, outside backs. Heart rate records were classified based
      on percent time spent in four zones (>95%, 85-95%, 75-84%, <75% HRmax). Blood
      lactate concentration was measured periodically throughout each match, with
      movements being classified as standing, walking, jogging, cruising, sprinting,
      utility, rucking/mauling and scrummaging. The heart rate data indicated that
      props and locks (58.4%) and back row forwards (56.2%) spent significantly more
      time in high exertion (85-95% HRmax) than inside backs (40.5%) and outside backs
      (33.9%) (P < 0.001). Inside backs (36.5%) and outside backs (38.5%) spent
      significantly more time in moderate exertion (75-84% HRmax) than props and locks
      (22.6%) and back row forwards (19.8%) (P < 0.05). Outside backs (20.1%) spent
      significantly more time in low exertion (<75% HRmax) than props and locks (5.8%)
      and back row forwards (5.6%) (P < 0.05). Mean blood lactate concentration did not
      differ significantly between groups (range: 4.67 mmol x l(-1) for outside backs
      to 7.22 mmol x l(-1) for back row forwards; P < 0.05). The motion analysis data
      indicated that outside backs (5750 m) covered a significantly greater total
      distance than either props and locks or back row forwards (4400 and 4080 m,
      respectively; P < 0.05). Inside backs and outside backs covered significantly
      greater distances walking (1740 and 1780 m, respectively; P < 0.001), in utility
      movements (417 and 475 m, respectively; P < 0.001) and sprinting (208 and 340 m,
      respectively; P < 0.001) than either props and locks or back row forwards
      (walking: 1000 and 991 m; utility movements: 106 and 154 m; sprinting: 72 and 94
      m, respectively). Outside backs covered a significantly greater distance
      sprinting than inside backs (208 and 340 m, respectively; P < 0.001). Forwards
      maintained a higher level of exertion than backs, due to more constant motion and
      a large involvement in static high-intensity activities. A mean blood lactate
      concentration of 4.8-7.2 mmol x l(-1) indicated a need for 'lactate tolerance'
      training to improve hydrogen ion buffering and facilitate removal following high
      intensity efforts. Furthermore, the large distances (4.2-5.6 km) covered during,
      and intermittent nature of, match-play indicated a need for sound aerobic
      conditioning in all groups (particularly backs) to minimize fatigue and
      facilitate recovery between high-intensity efforts.

PMID- 9756261
TI  - Springboard oscillation during hurdle flight.
AB  - The relative influences of board-tip rebound and fulcrum setting upon vertical
      board-tip oscillation during hurdle flight were investigated to gain insight into
      the mechanism by which highly skilled divers are able to make effective contact
      with the springboard. Data were collected on running dives executed by 3-m
      finalists at the 1995 World Diving Cup (men), the 1996 Olympic Games (women) and
      the 1996 US Junior Olympics (boys and girls). Analysis of the vertical board-tip
      patterns of motion during hurdle flight revealed substantial deviations from a
      regular damped oscillation, particularly during the first excursion above the
      horizontal. The latter was characterized by two peaks, the first resulting from
      upward momentum and the second due to the board's colliding with the fulcrum. A
      regression analysis of the senior divers' data indicated that 83.7% of the
      variance in hurdle flight time could be accounted for by the maximum height
      reached by the board-tip and only 3.6% by fulcrum setting. We conclude that,
      among senior divers, rebound of the springboard was the dominant factor
      influencing the length of time required for the board to complete its
      characteristic 2.25 and 2.50 cycles before take-off.

PMID- 9756262
TI  - The effect of industrial and agricultural pollution on human spermatogenesis.

PMID- 9756263
TI  - Time to switch from co-culture to sequential defined media for transfer at the
      blastocyst stage.

PMID- 9756264
TI  - Testicular sperm extraction and intracytoplasmic sperm injection.

PMID- 9756265
TI  - FIGO statements and world experience.

PMID- 9756266
TI  - Prevention of ovarian hyperstimulation syndrome: novel strategies.

PMID- 9756267
TI  - Infants conceived using in-vitro fertilization do not over-utilize health care
      resources after the neonatal period.
AB  - Health outcomes during the first year for 95 infants born following in-vitro
      fertilization (IVF) were compared with those of 79 naturally conceived controls
      whose mothers were of identical parity and similar age. Primigravid women were
      enrolled prospectively at 30 weeks gestation, perinatal and neonatal data were
      collected during pregnancy and following birth, and details of health care
      resource use were obtained from mothers at 4 and 12 months. Median (range) number
      of medical problems during the first year tended to be less for IVF infants, 4 (0
      41) versus 5 (0-12) (P = 0.07), whilst total number of visits to health care
      workers was similar for IVF and control infants, 19 (2-47) versus 19 (1-47). IVF
      infants were more likely to have an excessive number of visits to Early Childhood
      Health Care Centres [odds ratio (OR; 95% confidence interval, CI) = 2.44 (1.11
      5.56)], but less likely to have an excessive number of visits to general medical
      practitioners [OR = 0.45 (0.22-0.93)] and other health care workers [OR = 0.48
      (0.23-0.99)]. These data provide some degree of reassurance about medium-term
      health outcomes for children conceived using IVF. Although they are more likely
      to utilize the resources of neonatal intensive care units, IVF infants do not
      appear to have an increased number of medical problems or to over-utilize health
      care resources during the remainder of their first year of life.

PMID- 9756268
TI  - Persistent pregnanediol glucuronide secretion after gonadotrophin suppression
      indicates adrenal source of progesterone in premature ovarian failure.
AB  - A 2-3 fold higher urinary pregnanediol glucuronide excretion has been observed in
      women with premature ovarian failure, compared with age-appropriate menopausal
      women. Progesterone, the precursor of urinary pregnanediol glucuronide, is a
      secretory product of either adrenal or ovarian origin. We postulated that
      suppression of pituitary gonadotrophin secretion by down-regulation with a long
      acting gonadotrophin-releasing hormone agonist, leuprolide acetate, would
      decrease ovarian but not adrenal pregnanediol glucuronide. This would demonstrate
      a major difference in the ovarian hormonal milieu of these two groups of women.
      Four volunteers with premature ovarian failure collected daily first morning
      voided urine samples for 1 month prior to leuprolide acetate administration.
      Leuprolide acetate was then administered monthly for 3 months while continuing
      daily urinary collection. Luteinizing hormone (LH), follicle stimulating hormone
      (FSH), and pregnanediol glucuronide were measured in all samples and normalized
      for creatinine. Comparisons of pre- and post-median values for luteinizing
      hormone (LH), FSH, and pregnanediol glucuronide were made using the Wilcoxon rank
      sum test. This demonstrated significant suppression of both LH and FSH.
      Pregnanediol glucuronide, however, did not demonstrate a significant decline,
      strongly implying an adrenal source of the enhanced excretion. The decreased
      pregnanediol glucuronide noted in age-appropriate menopausal women compared with
      premature ovarian failure is likely to be a reflection of adrenal ageing.

PMID- 9756269
TI  - Steroidogenesis in luteinized granulosa cell cultures varies with follicular
      priming regimen.
AB  - During follicular development, a co-ordinated gonadotrophin and endocrine
      environment is believed to be essential for normal function of the resulting
      corpus luteum. Whether differences in the gonadotrophins used to promote
      follicular development can have lasting effects on granulosa cells after they
      have undergone luteinization and culture, remains to be studied. We measured
      steroid production under basal and human chorionic gonadotrophin (HCG)
      stimulation in short and long term cultures of luteinizing granulosa cells
      obtained from normal ovulatory women undergoing assisted folliculogenesis with
      either human menopausal gonadotrophin (HMG) or follicle stimulating hormone
      (FSH). Basal progesterone and oestradiol production by luteinized granulosa cells
      obtained from follicles stimulated to develop with FSH was significantly greater
      than that from HMG derived follicles (P < 0.001). In short term cultures,
      treatment with 10 IU HCG caused a 10-fold increase in progesterone release by
      cells from FSH stimulated follicles, whereas cells of HMG origin produced only 5
      fold more progesterone (P < 0.0001). In cultures that were maintained for 2
      weeks, progesterone secretion was reduced, but a similar trend in HCG
      responsiveness was observed. These experiments demonstrate that the composition
      of the gonadotrophins used to promote follicular development in vivo leads to
      differences in granulosa cell steroidogenesis which are evident after
      luteinization and culture. They additionally support the notion that the
      environment of follicular development will be reflected in the resulting corpus
      luteum.

PMID- 9756270
TI  - Elevated concentrations of angiogenin in serum and ascitic fluid from patients
      with severe ovarian hyperstimulation syndrome.
AB  - This study was conducted to investigate the possible role of angiogenin in the
      pathogenesis of ovarian hyperstimulation syndrome (OHSS). The study group
      consisted of 10 healthy women who developed severe OHSS (group A) following
      ovarian stimulation by a long protocol of gonadotrophin-releasing hormone
      analogues/human menopausal gonadotrophin for in-vitro fertilization. A control
      group B (n = 10) underwent stimulation by the same protocol and did not develop
      OHSS. Blood samples were taken from group A on day of admission to hospital for
      treatment of OHSS and, in group B, 1 week after oocyte retrieval. In group A,
      ascitic fluid was routinely aspirated as a treatment for severe OHSS, and a
      peritoneal fluid sample was aspirated transvaginally before oocyte retrieval in
      group B. In group A, the mean serum angiogenin, the mean ascitic fluid
      angiogenin, the mean serum oestradiol concentration on day of human chorionic
      gonadotrophin and the mean haematocrit were 8390 +/- 6836 ng/ml, 2794 +/- 1024
      ng/ml, 6300 +/- 2450 pg/ml and 46.6 +/- 4.4 respectively, as compared with 234 +/
      91 ng/ml, 254 +/- 105 ng/ml, 1850 +/- 1100 pg/ml and 36.8 +/- 4.6 in group B
      respectively. The differences between groups were highly significant for all
      parameters. Angiogenin seems to be strongly associated with the formation of
      neovascularization responsible for the development of OHSS.

PMID- 9756271
TI  - Peri-ovarian adhesions interfere with the diffusion of gonadotrophin into the
      follicular fluid.
AB  - In previous studies, patients with severe peri-ovarian adhesions have been found
      to show low pregnancy rates and a poor response to gonadotrophin stimulation
      during in-vitro fertilization (IVF) treatment. The purpose of this retrospective
      pharmacokinetic study was to assess the diffusion of exogenous human chorionic
      gonadotrophin (HCG) in patients with peri-ovarian adhesions by examining the
      concentration of exogenous HCG in the follicular fluid in patients undergoing
      down-regulation and IVF due to infertility. The patients underwent laparoscopic
      examination for the scoring of peri-ovarian adhesions (using the classification
      of adnexal adhesions adopted by the American Fertility Society, a score of 0
      means no adhesions, and a score of 32 represents bilateral expanded dense
      adhesions). Oocytes were recovered after human menopausal gonadotrophin-human
      chorionic gonadotrophin (HMG-HCG) stimulation with gonadotrophin-releasing
      hormone agonist. Serum and follicular fluid were collected at the time of oocyte
      recovery for measuring the HCG ratio (the follicular HCG concentration to the
      serum HCG concentration; a reflection of the diffusion of exogenous
      gonadotrophin) by time-resolved fluoroimmunoassay. A negative correlation was
      found between the number of oocytes recovered and the peri-ovarian adhesion score
      (r = -0.62, P < 0.01). In a given patient, the follicular HCG concentration was
      always lower than the serum HCG at the time of oocyte recovery. The HCG ratio in
      all samples was 0.9 or less (0.51 +/- 0.20; range, 0.09-0.90). Significant
      negative correlations were found between the peri-ovarian adhesion score and both
      the follicular HCG concentration (r = -0.80, P < 0.01) and the HCG ratio (r = 
      0.75, P < 0.01). In conclusion, severe peri-ovarian adhesions interfered with the
      diffusion of exogenous gonadotrophin into the follicular fluid during IVF
      treatment. Thus, the diffusion of exogenous gonadotrophin into the follicular
      fluid may represent a new parameter in the assessment of ovarian blood flow and
      IVF outcome.

PMID- 9756272
TI  - Effects of repeated abdominal paracentesis on uterine and intraovarian
      haemodynamics and pregnancy outcome in severe ovarian hyperstimulation syndrome.
AB  - The aims of this study were to investigate the effects of paracentesis on uterine
      and intraovarian haemodynamics by colour Doppler ultrasound and the influences of
      repeated paracentesis on pregnancy outcome in severe ovarian hyperstimulation
      syndrome (OHSS). Forty-one abdominal paracenteses were performed on seven
      pregnant women with tense ascites and eight thoracocenteses were performed on
      three pregnant women with pleural effusion. Pulsatility index (PI) and maximum
      peak systolic velocity (MPSV) of uterine and intraovarian arteries were measured
      before and after each intervention. The mean PI of uterine arteries was decreased
      significantly after paracentesis, but not after thoracocentesis. Furthermore,
      uterine PI was decreased in 13 out of 14 (92.9%) paracenteses with <2500 ml
      ascites removed, compared with eight out of 13 (61.5%) with >2500 ml ascites
      removed. After paracentesis, there were no significant changes in the
      intraovarian PI and MPSV in either group. The 24-hour urine output increased
      significantly in the paracentesis group, but not in the thoracocentesis group.
      There were no significant changes in haematocrit and electrolytes as a result of
      paracentesis. However, gradual falls in serum total proteins and albumin
      concentrations were observed in all patients after repeated paracentesis,
      necessitating post-paracentesis albumin infusion. There was no significant
      difference in miscarriage rates between the two groups. We conclude that repeated
      abdominal paracentesis increases uterine perfusion and has no adverse effects on
      pregnancy outcome in severe OHSS. Extraction of 2500 ml of ascitic fluid did not
      impair uterine perfusion.

PMID- 9756273
TI  - Ovarian hyperstimulation syndrome (OHSS) in a spontaneous pregnancy with fetal
      and placental triploidy: information about the general pathophysiology of OHSS.
AB  - An ovarian hyperstimulation syndrome (OHSS) in spontaneous pregnancies is a very
      rare event. Hence, clinicians might make wrong decisions, such as laparotomy,
      because of suspicion of an ovarian carcinoma, or severe complications such as
      renal insufficiency may develop because the diagnosis and treatment of OHSS are
      delayed. Here we report a case of a woman in the 15th week of gestation,
      presenting with a partial hydatidiform mole and a triploidy of fetus and
      placenta, with an ongoing and severe OHSS even after legal induced abortion. A
      low vascular endothelium growth factor (VEGF) concentration (50 ng/ml) was
      measured when human chorionic gonadotrophin (HCG) exceeded 1000 IU/l and was
      followed by VEGF concentrations >900 ng/ml, when the OHSS developed. The
      literature on spontaneous pregnancies associated with OHSS is reviewed, and
      possible reasons for the clinical course presented in this study and the reviewed
      reports are discussed. The findings in this case contribute to our theory that
      VEGF is a causative factor of OHSS, but has no impact on the course of this
      disease.

PMID- 9756274
TI  - Moderate ovarian hyperstimulation syndrome complicated by deep cerebrovascular
      thrombosis.
AB  - This report describes two cases that developed moderate ovarian hyperstimulation
      syndrome (OHSS) without evidence of haemoconcentration. Both patients developed
      serious cerebrovascular thrombosis resulting in hemiparesis, and recovered after
      treatment with anticoagulants. This report emphasizes that other factors may
      contribute to vascular thrombosis, and illustrates that cerebrovascular accidents
      may complicate even moderate OHSS.

PMID- 9756275
TI  - Female patients with cystic fibrosis suffer from reproductive endocrinological
      disorders despite good clinical status.
AB  - Ten women with cystic fibrosis (CF) were evaluated with regard to hormonal
      profiles during a natural and a clomiphene citrate (CC) stimulated cycle. Five of
      the women were found to be anovulatory during a natural cycle. All women except
      one did respond with ovulation to CC stimulation indicating adequate ovarian
      response. Neither did they show increased follicle-stimulating hormone (FSH)
      concentrations on day 10 after CC treatment confirming normal ovarian reserve.
      Clinically the anovulatory women differed from the ovulating in two aspects: more
      profound essential fatty acid deficiency (EFAD) and higher peak/basal insulin
      response during an oral glucose tolerance test. The anovulatory women had
      significantly lower luteal oestradiol and progesterone but higher total
      testosterone concentrations when compared to healthy controls and the ovulatory
      CF women. The pathological insulin response and high testosterone concentrations
      resemble those seen in women with polycystic ovarian (PCO) syndrome. However, the
      CF patients in our study had normal ovaries, as deduced from ultrasound
      examination and normal luteinizing hormone (LH)/FSH ratio. It is suggested that
      EFAD as well as hypersecretion of insulin may be of importance for the observed
      ovarian dysfunction. Further studies are needed to evaluate the relation between
      ovulatory mechanisms and EFAD in CF women as well as studies to compare
      anovulatory CF women with women with PCO syndrome.

PMID- 9756276
TI  - Screening male intracytoplasmic sperm injection candidates for mutations of the
      follicle stimulating hormone receptor gene.
AB  - Follicle stimulating hormone (FSH) is considered to be essential for
      spermatogenesis. Therefore, genetic abnormalities of FSH signalling on testicular
      Sertoli cells would be expected to affect sperm production negatively in males.
      Inactivating FSH receptor mutations have been reported earlier in both males and
      females. All affected males had elevated FSH serum concentrations and abnormal
      sperm parameters. We postulated that inactivating FSH receptor mutations might be
      a cause of oligozoospermia or azoospermia and reviewed the clinical data of 151
      male intracytoplasmic sperm injection (ICSI) candidates with special attention to
      FSH serum concentrations. The exclusion criteria for mutation screening of the
      FSH receptor gene were: a history of operative sterilization or testicular
      malignancy, congenital abnormality other than cryptorchidism, and a chromosomal
      aberration or a Y-chromosome microdeletion. The inclusion criteria were: male
      (ICSI candidate) with azoospermia or oligoasthenoteratozoospermia (OAT) and
      elevated FSH serum concentrations. In total, 23 males with OAT and five males
      with azoospermia were tested for mutations of the coding sequences and the intron
      exon boundaries of the FSH receptor gene by polymerase chain reaction (PCR)
      followed by single strand conformation polymorphism analysis (SSCP). Neutral
      polymorphisms were readily detected using this technique in both probands and
      controls. None of the 28 selected patients showed a pathogenic FSH receptor
      mutation. Mutations in the FSH receptor gene are not a common cause of
      infertility in ICSI candidates.

PMID- 9756277
TI  - Second look after laparoscopic myomectomy.
AB  - The goal of this study was to assess the risk of adhesions after laparoscopic
      myomectomy. To this end our enquiry was based on observations with a prospective
      collection of data. Between October 26, 1990 and October 1, 1996, 45 patients
      underwent a second look after laparoscopic myomectomy. Seventy-two myomectomy
      sites were checked. The overall rate of postoperative adhesion was 35.6% per
      patient. The rate of adhesions per myomectomy site was 16.7%. The factors which
      influenced the occurrence of an adhesion on the myomectomy site were posterior
      location of the myoma and the existence of sutures. The rate of adhesions on the
      adnexa after laparoscopic myomectomy was 24.4%. The factors which influenced the
      occurrence of adnexal adhesions were another surgical procedure carried out at
      the same time, the existence of adhesions prior to the operation and posterior
      location of the myoma. The rate of adhesions after laparoscopic myomectomy is low
      and the adhesions rarely involved the adnexa. We recommend that a second-look
      laparoscopy be carried out systematically after laparoscopic myomectomy in
      patients desiring pregnancy.

PMID- 9756278
TI  - Ultrasound tracking of the movement of embryo-associated air bubbles on standing
      after transfer.
AB  - The aim of this study was to investigate whether standing upright shortly after
      embryo transfer has any potential to affect the position of embryos transferred
      to the uterine cavity during treatment with in-vitro fertilization (IVF). This
      was assessed by ultrasound-guided tracking of embryo-associated air within the
      uterine cavity. A prospective study of 93 patients undergoing 101 consecutive
      embryo transfers in an IVF programme was carried out. Transvaginal ultrasound
      guided embryo transfer was performed with a second ultrasound in standing
      position immediately after transfer, allowing the movement of embryo-associated
      air to be assessed. No movement occurred in 94.1% (95/101) of transfers, movement
      of <1 cm in 4.0% (4/101) of transfers and movement of 1-5 cm in 2.0% (2/101)
      transfers. No movement of embryo-associated air out of the uterine cavity, either
      into the cervix or the intramural portion of the Fallopian tube, was seen.
      Standing shortly after embryo transfer does not play a significant role in the
      final position of embryo-associated air and is unlikely to be a factor in
      determining the position of embryos transferred to the uterine cavity during
      treatment with IVF.

PMID- 9756279
TI  - Sequential clomiphene citrate and human menopausal gonadotrophin with
      intrauterine insemination: the effect of patient age on clinical outcome.
AB  - The purpose of this investigation was to examine the influence of female and male
      patient age on pregnancy rates with sequential clomiphene citrate (CC) and human
      menopausal gonadotrophin (HMG) ovulation induction with intrauterine insemination
      (IUI) therapy after previous CC and IUI treatment failure. A total of 208
      patients previously unable to conceive with CC/IUI therapy underwent 416
      treatment cycles of sequential CC/HMG with IUI at a university fertility centre
      between May, 1991 and August, 1995. Clinical pregnancy rates, live birth rates,
      and the effect of female and male partner chronological age were retrospectively
      examined. Treatment with sequential CC/HMG with IUI resulted in clinical
      pregnancy rates ranging from 5.9 to 23.1% despite previous CC/IUI treatment
      failure. Clinical pregnancy rates, live birth rates, and cumulative pregnancy
      rates declined significantly in female patients > or = 35 years of age compared
      to those < 35 years of age. A statistically significant decline in clinical
      pregnancy rates could not be demonstrated as a function of increasing male
      partner age. Pregnancy rates in patients undergoing ovulation induction with
      sequential CC/HMG with IUI decline significantly with increasing female partner
      age.

PMID- 9756280
TI  - A prospective analysis of the accuracy of the TEST-yolk buffer enhanced hamster
      egg penetration test and acrosin activity in discriminating fertile from
      infertile males.
AB  - The aim of this study, based on a prospective analysis, was to evaluate the
      accuracy of the TEST-yolk buffer enhanced hamster egg penetration test (HEPT) and
      acrosin activity in discriminating fertile from infertile males as compared with
      the conventional semen profile. The incidence of spontaneous pregnancies was
      monitored during a follow-up period ranging between 18-24 months in 62 couples
      without untreatable female infertility. The diagnostic accuracy of the HEPT was
      significantly higher than that of the conventional semen profile, as evaluated
      with fitted ROC curves. The best discriminatory ability was exhibited by a
      penetration index (penetrations/oocyte) of 2 as cut-off value. In our series it
      gave a positive predictive value of 77.8% and a negative predictive value of
      92.3%. Acrosin activity did not show a discriminating power significantly higher
      than the conventional semen profile, but an acrosin activity <20 microIU/10(6)
      spermatozoa was found only among patients who did not achieve a pregnancy. In
      conclusion, this prospective analysis indicates that the TEST-yolk buffer
      enhanced HEPT constitutes a significant improvement over the conventional semen
      profile in discriminating fertile from infertile males. Acrosin activity could
      provide a useful adjunctive test because of the high negative predictive value of
      its poor results.

PMID- 9756281
TI  - Occupational heat exposure and male fertility: a review.
AB  - In humans, as in most mammals, spermatogenesis is temperature dependent. This
      temperature dependence has been clearly demonstrated by several experimental
      studies showing that artificial increases in scrotum or testicle temperature in
      fertile men reduce both sperm output and quality. Our knowledge of the effects of
      occupational heat exposure on male fertility comes mostly from a small number of
      epidemiological studies. We conducted an extensive review of these published
      reports, focusing on methodology and design (retrospective or prospective;
      reference group; number of subjects) and principal results (using several
      indicators such as the time taken to obtain a pregnancy or sperm
      characteristics). We concluded that occupational heat exposure is a significant
      risk factor for male infertility, affecting sperm morphology and resulting in
      delayed conception. The limits and biases involved in this type of research are
      also discussed.

PMID- 9756282
TI  - Intracytoplasmic sperm injection as a routine indication in low responder
      patients.
AB  - The aim of this study was to determine if a low response to gonadotrophin
      stimulation could be considered as an indication for intracytoplasmic sperm
      injection (ICSI). This prospective study included a total of 96 non-male
      infertile couples with six or fewer retrieved oocytes, who underwent 104 in-vitro
      fertilization (IVF) cycles between January 1996 and April 1997. They were
      randomly divided into two groups for fertilization, one by IVF and the other by
      ICSI. Groups were compared in terms of fertilization rates, fertilization
      failure, embryo quality, embryos transferred and reproductive outcome. ICSI
      provided similar fertilization rates per inseminated oocyte (77.7 versus 70.2%)
      and per obtained oocyte (56.5 versus 58.8%) as IVF. Furthermore, equal numbers
      (2.2 versus 2.5) and quality of embryos were obtained and comparable pregnancy
      (21.1 versus 17.3%) and implantation (14.0 versus 11.1%) rates. Neither the
      number of retrieved oocytes, nor patient age was relevant for the fertilization
      rates obtained with both techniques. The number of cases with complete
      fertilization failure was similar in both procedures. We conclude that the
      technique of fertilization is not related to the reproductive outcome of low
      responders, and the routine use of ICSI is not indicated.

PMID- 9756283
TI  - Combined fresh and frozen embryo transfer resulting in a twin delivery.
AB  - We report the delivery of non-identical twins resulting from the combined
      transfer of one fresh and one frozen embryo to a 31 year old patient. To our
      knowledge, this is the first reported case where both a fresh and a frozen embryo
      implanted in the same cycle led to non-identical twins. We conclude that
      supernumerary embryos after in-vitro fertilization should be frozen and used in
      subsequent cycles, with implantation potentials as high as fresh embryos. The
      possibility of mixing fresh and frozen embryos, though rarely needed, should be
      considered, particularly when there is only one fresh embryo available for
      transfer.

PMID- 9756284
TI  - A chronic, low-dose regimen of the antiprogestin ZK 137 316 prevents pregnancy in
      rhesus monkeys.
AB  - Continual administration of low doses of the antiprogestin ZK 137 316 was
      previously reported to permit ovarian/menstrual cyclicity, but disrupt
      endometrial growth in macaques. The contraceptive efficacy of this regimen was
      tested in female rhesus monkeys (10 per group) treated daily with vehicle
      (controls), 0.01 or 0.03 mg ZK 137 316 per kg body weight for 30 days before and
      during continual co-habitation with males of proven fertility. Treatment
      continued until confirmation of pregnancy or for 5 months after pair-housing with
      males. Mating and vaginal sperm were evident in all females. A cumulative
      pregnancy rate of 90% (9/10) was observed in the controls. Of the 10 animals
      receiving 0.01 mg/kg, four conceived during the first 2 months of pairing (P =
      0.06) with no further conceptions. No pregnancies were observed in the 0.03 mg/kg
      group (P < 0.01). Timely, overt menses occurred at a higher frequency in the 0.01
      mg/kg group than the 0.03 mg/kg group. However, corpora lutea were present in
      ovaries from both groups during the last treatment cycle, indicating that ovarian
      cycles occurred. Thus, chronic administration of low-dose ZK 137 316 that permits
      continued ovarian cyclicity and a high incidence of timely menses, prevents
      pregnancy in non-human primates. This regimen may provide a novel method of
      contraception for women.

PMID- 9756285
TI  - Effect of seminal plasma on capacitation and hyperactivation in human
      spermatozoa.
AB  - While hyperactivated motility is known to be a concomitant of capacitation, and a
      prerequisite for fertilization, the specific interdependence of capacitation and
      hyperactivation in human spermatozoa has not been investigated. This study was
      designed to determine the effect of seminal plasma contamination on the
      expression of hyperactivated motility and the relationship between
      hyperactivation and capacitation, since seminal plasma contains decapacitation
      factor(s). Seminal plasma was obtained by centrifugation of aliquots of liquefied
      semen layered over 1.5 ml 40.5% Percoll and mixed with human tubal fluid (HTF)
      medium containing 30 mg/ml human serum albumin (HSA) (HTF) to a final
      concentration of 5% (v/v) seminal plasma (SP). Motile spermatozoa were isolated
      from the remainder of the semen by swim-up into either HTF or SP medium. Samples
      were taken from each treatment immediately post-harvest (0 h) and after 60 min at
      37 degrees C (1 h) for hyperactivation and capacitation assessment. The
      treatments were then divided into two portions, centrifuged and resuspended in
      either HTF or SP, giving HTF control and SP control treatments and two crossover
      treatments, 1 h HTF then 1 h SP (H/SP) and 1 h SP then 1 h HTF (SP/H). All tubes
      were incubated for a further 60 min at 37 degrees C before aliquots were taken
      for hyperactivation and capacitation assessments. Hyperactivation was estimated
      using an IVOS v10.6t (Hamilton Thorne Research, Beverly, MA, USA) 60 Hz CASA
      instrument, and capacitation was estimated using the chlortetracycline (CTC)
      method. The presence of seminal plasma in the capacitation medium for 60-120 min
      post-swim-up inhibited the development of hyperactivated motility. This
      inhibition was reversible, and was not prevented by preincubation for 1 h in HTF
      medium. There was no difference in the CTC binding patterns between treatments at
      2 h, indicating that the capacitation-associated membrane changes were not
      affected by the presence of a low concentration of seminal plasma. There was no
      correlation between percentage capacitated and percentage hyperactivated
      spermatozoa for any treatment. Since the proportions of hyperactivated
      spermatozoa and capacitated spermatozoa were not related, we conclude that the
      processes leading to hyperactivation and to the membrane changes associated with
      capacitation are not tightly interlinked and consider this finding to be due to
      hyperactivated motility being associated with flagellar movement, while the CTC
      assay assesses changes in the Ca2+ levels of the sperm head plasma membrane.

PMID- 9756286
TI  - Update on treatment of varicocele: counselling as effective as occlusion of the
      vena spermatica.
AB  - This prospective randomized study was performed in order to investigate the
      effects of interventive treatment or counselling on pregnancy rates in infertile
      couples in whose male partners a varicocele was diagnosed. The present report
      extends a previous study using the same design. A total of 125 couples were
      included in the current study while the previous report comprised 95 couples.
      Couples fulfilling the inclusion criteria were allocated randomly either to
      interventive treatment (surgical ligation or angiographic embolization of the
      spermatic vein) (n = 62) or to counselling as the sole treatment (n = 63).
      Couples were followed over the subsequent 12 months and seen at 3-monthly
      intervals. At the end of the 12 month period pregnancy rates, as the main outcome
      measure, were 29% in the group given interventive treatment and 25.4% in the
      counselled group and were not significantly different. The only significant
      difference found, regardless of treatment modality, was the wives' age at
      admittance: the 34 wives achieving a pregnancy were 28.8 +/- 0.6 years (mean +/-
      SE) old while the 91 non-pregnant wives were 31.2 +/- 0.3 years old (P < 0.05).
      The study suggests that regular counselling of the infertile couples is as
      effective as interventive treatment of varicoceles in achieving pregnancies.

PMID- 9756287
TI  - Comparison of various methods of processing human cryopreserved-thawed semen
      samples.
AB  - We compared the efficacy of various methods of processing cryopreserved-thawed
      samples for the recovery of functionally adequate spermatozoa as assessed by the
      response to the sperm stress test (SST), an index of temperature activated sperm
      membrane lipid peroxidation, and immediate and delayed changes in sperm viability
      and motion parameters. Donor semen samples (n = 28) were cryopreserved-thawed and
      divided into six equal parts, one part was used as control and the remaining
      parts were used to compare five methods of sperm processing as follows: direct
      Percoll gradient processing, washing by one-step or stepwise addition of the
      washing medium followed by Percoll processing, and washing by one-step or
      stepwise addition of the washing medium. Additional samples (n = 10) were
      evaluated for the immediate and delayed (6 h at 37 degrees C) impact of one-step
      and stepwise washing (without Percoll separation). Compared with wash-only
      methods, samples processed using Percoll had a significantly higher SST score (P
      = 0.001), motility, rapid spermatozoa (>50 microm/s), curvilinear velocity and
      motility index (P < 0.001). Comparing various Percoll methods, direct Percoll
      processing resulted in the highest number of motile spermatozoa recovered (P <
      0.00001) and a higher SST score based on curvilinear velocity (P = 0.001).
      Stepwise washing gave a significantly higher number of motile spermatozoa (P <
      0.001) but with a significantly lower SST score based on the concentration of
      motile spermatozoa (P = 0.001), motility (P = 0.001) and motility index (P =
      0.01). Sperm viability and motion parameters after 6 h of incubation showed no
      difference between one-step and stepwise washing. In conclusion, compared with
      wash-only methods, Percoll processed samples resulted in the recovery of
      spermatozoa with superior quality as assessed by SST and motion analysis. One
      step washing of the samples gave an overall comparable recovery compared to the
      samples prepared stepwise. Having significantly higher SST scores, similar
      viability and the maintenance of motility, one-step washing may be a better
      method of processing thawed samples than the stepwise washing.

PMID- 9756288
TI  - The outcome of in-vitro fertilization treatment by egg donation and
      intracytoplasmatic sperm injection for severe male factor infertility: a
      preliminary report.
AB  - Due to a paucity of donated eggs, we have excluded, until recently, couples with
      severe male factor infertility from our egg donation programme, except for those
      who accepted insemination with donor spermatozoa. The purpose of this study was
      to assess the feasibility of a shared in-vitro fertilization (IVF)-embryo
      transfer treatment whenever the recipients have severe
      oligoasthenoteratozoospermia (OTA) and need intracytoplasmic sperm injection
      (ICSI) for egg fertilization. The results from 163 consecutive couples with
      ovarian failure who underwent 273 cycles of IVF with donated eggs and augmented
      with ICSI were analysed. The rate of diploid fertilization was 54.7%; in 92.3% of
      the cycles, at least one embryo was available for transfer. Forty-seven clinical
      pregnancies were achieved, representing 18.6% conceptions per transfer. The
      highest pregnancy rate was achieved in menopausal patients aged 40-45 years
      (26.2% per cycle) and the lowest in patients >45 years old (10.8% per cycle, P =
      0.03). Overall, 28.8% of the couples achieved a clinical pregnancy. A total of
      196 treatment cycles resulted in 46 clinical pregnancies (23.5%) among the
      donors. No statistical differences were found in pregnancy rate achieved by the
      donors when compared with the recipients. We conclude that ICSI with egg donation
      is a reliable treatment in patients with ovarian failure and severe OTA.

PMID- 9756289
TI  - Semen quality: is there a paternal effect on pregnancy outcome in in-vitro
      fertilization/intracytoplasmic sperm injection?
AB  - The objective of this study was to investigate the role of the spermatozoon
      (paternal effects) on implantation and pregnancy outcome in in-vitro
      fertilization/intracytoplasmic sperm injection (IVF/ICSI). Male individuals of
      three types were analysed: infertile men with oligoasthenoteratozoospermia (OAT),
      infertile men with normozoospermia and fertile men (donors). Female counterparts
      were judged to have comparable egg quality within two groups studied, i.e.
      infertile women with pure mechanical (tubal) infertility and recipients of donor
      eggs. There were significantly higher differences in implantation and pregnancy
      rates in groups using donor spermatozoa and donor egg recipients. Analyses of key
      set groups revealed a trend toward a poorer implantation and pregnancy outcome
      when comparing OAT versus normozoospermic patients within IVF, but not within
      ICSI treatments, in couples with tubal infertility. In couples who were
      recipients of donor eggs, no differences were observed between OAT patients
      treated by ICSI and normozoospermic patients treated with IVF. No significant
      differences were observed in miscarriage rates within any groups studied. In
      conclusion, the poorer results observed in OAT patients undergoing IVF may be
      secondary to spermatozoal effects due to a high insemination concentration.
      Overall, there does not seem to be a significant effect of severe male
      infertility (OAT) on implantation and pregnancy outcome. However, this does not
      preclude that specific sperm aberrations may exert a negative effect on
      embryogenesis and therefore on implantation potential following assisted or in
      vivo reproduction.

PMID- 9756290
TI  - Exogenous influences on human fertility: fluctuations in sperm parameters and
      results of in-vitro fertilization coincide with conceptions in the normal
      population.
AB  - Intra- and interindividual short-term fluctuations of sperm parameters were
      observed in assisted reproduction patients, paralleled by respective fluctuations
      of the in-vitro fertilization (IVF) results. To test whether the fertility
      fluctuations observed in the clinic were representative for the overall
      population, birth statistics of two normal subpopulations (urban and rural) were
      studied. There were highly significant parallels in the fluctuations of the
      monthly deliveries in both normal subpopulations. Also, there was a significant
      correlation when the fluctuation of sperm parameters in IVF patients was compared
      with those of a control group. Furthermore, delivery fluctuations in the overall
      population were significantly paralleled by fluctuations in sperm parameters and
      IVF results around the conception time of these deliveries. In all groups, the
      pattern and amplitude of the short-term fluctuations varied from year to year.
      Frequently observed peaks in late autumn gave rise to the appearance of a semi
      seasonal variation in fertility. The existence of an external influence on
      overall male gamete quality must be postulated, which has considerable influence
      on the IVF results. This short-term influence might be causally linked to the
      factors responsible for the previously found annual variation in human fertility
      and possibly for the long-term changes in human reproductive function.

PMID- 9756291
TI  - Selenium in human male reproductive organs.
AB  - The objective of the study was to obtain information on the concentration and
      distribution of selenium throughout the human male reproductive tract. Material
      was removed at autopsy from 41 men who had died suddenly and unexpectedly. Semen
      samples were also provided from 184 men attending an andrology clinic for
      fertility investigation and from 32 healthy volunteers. Significant positive
      correlations in the selenium concentration were demonstrated between the
      different reproductive organs, the testis having the highest concentrations. No
      correlation was found between the concentration of selenium in the genital organs
      and liver, kidney or blood, suggesting that its uptake and/or biochemical
      activity in the reproductive organs may be controlled by similar mechanisms not
      shared by the other organs. No significant age-dependent changes could be
      detected in tissue selenium concentrations. In a group of men under fertility
      investigation, a significant positive correlation was obtained between seminal
      plasma concentrations of selenium and concentrations of spermatozoa in the same
      ejaculate. A significant positive correlation between concentrations of zinc and
      selenium in the same ejaculates indicated that selenium may arise largely from
      the prostate gland.

PMID- 9756292
TI  - Triplet pregnancy and delivery after intracytoplasmic injection of round-headed
      spermatozoa.
AB  - Intracytoplasmic sperm injection (ICSI) of round-headed spermatozoa into mature
      oocyte resulted in normal fertilization, embryo development and pregnancy in a 28
      year old female. The husband had a long history of primary infertility. Three
      ICSI attempts were carried out and fertilization and embryo development occurred
      in all trials. However, only the third trial led to a pregnancy, which proved to
      be quadruplet after the transfer of four embryos. One embryo vanished and the
      remaining triplets were delivered at 35 weeks of gestation by Caesarean section.
      Two of the babies, a boy weighing 2000 g and a girl weighing 2250 g at birth were
      discharged in a good condition 1 week after delivery and the third baby, a boy
      weighing 1550 g, was discharged 3 weeks after delivery.

PMID- 9756293
TI  - Insulin-like growth factor binding protein-3 mRNA expression in endothelial cells
      of the primate corpus luteum.
AB  - Luteinization is associated with endothelial cell proliferation as part of the
      extensive angiogenesis necessary to maintain corpus luteum function. However,
      following luteal demise, the vasculature regresses and the endothelial cells
      disappear. In the rat corpus luteum, the endothelial cells express high
      concentrations of insulin-like growth factor-binding protein-3 (IGFBP-3) during
      luteolysis, suggesting a role of IGFBP-3 during endothelial cell loss. The aim of
      the present study was to determine the occurrence and location of the messenger
      ribonucleic acid (mRNA) for IGFBP-3 in the primate corpus luteum, and to
      determine whether or not induction of luteal regression is associated with
      changes in localization of the message. Marmoset corpora lutea were studied
      throughout the cycle. The effects of induced luteolysis were examined 12 h or 24
      h after treatment with either a gonadotrophin-releasing hormone antagonist or a
      prostaglandin F2alpha analogue, administered during the mid-luteal phase. High
      IGFBP-3 expression was recorded in the endothelial cells of the majority of
      microvessels and a minority of capillaries surrounding the lutein cells in all
      functionally active corpora lutea. Expression declined markedly in regressing
      corpora lutea of the late follicular phase. Expression of the IGFBP-3 mRNA in
      lutein cells in the control corpus luteum was extremely rare. There were no major
      differences in the degree and pattern of IGFBP-3 expression as a consequence of
      induced luteal regression although there was an apparent increase in the number
      of capillary endothelial cells expressing. Induction of luteolysis resulted in
      expression in a minority of lutein cells. These results support the concept that
      IGFBP-3 has an autocrine/paracrine role in regulating various cell types in the
      primate corpus luteum, including endothelial cells. However, expression of IGFBP
      3 mRNA throughout the luteal phase suggests it may regulate angiogenesis and
      luteal function rather than endothelial cell death and luteolysis.

PMID- 9756294
TI  - Leukocytes in normal-cycling human ovaries: immunohistochemical distribution and
      characterization.
AB  - We investigated, using an image analysis system, the immunohistochemical
      localization of leukocyte subpopulations and human leukocyte antigen (HLA)-DR in
      30 normal-cycling human ovaries in order to better understand local immunological
      events in human ovaries. All subtypes of T lymphocytes examined (CD3+, CD4+ and
      CD8+ cells) were sporadically observed in the stroma and theca layers of
      follicles throughout the menstrual cycle (ranging from 4.32 to 6.25 cells/10(-7)
      m2, 1.67 to 3.33 cells/10(-7) m2 and 2.33 to 3.44 cells/10(-7) m2, respectively
      for the three subtypes), and subsequently, increased in number in atretic
      follicles (78.70 +/- 6.90, 31.13 +/- 2.54 and 43.31 +/- 3.35). After ovulation,
      the number of T lymphocytes was markedly low in the early and mid corpus luteum
      (13.88 +/- 1.62, 4.18 +/- 0.50 and 6.53 +/- 0.45). The number increased in the
      late corpus luteum, and was highest in the late degenerating corpus luteum
      (255.67 +/- 27.10, 102.12 +/- 7.80 and 137.34 +/- 12.50). HLA-DR was sporadically
      positive in fibroblasts in the stroma and theca layers of follicles (means ranged
      from 1.25 to 1.82 cells/10(-7) m2), and increased in atretic follicles (24.68 +/-
      2.25). HLA-DR+ cells were markedly low in the early and mid corpus luteum (2.16
      +/- 0.88), increased in the late corpus luteum, and reached a plateau in the late
      degenerating corpus luteum (121.84 +/- 17.73). The great majority of these
      increased HLA-DR+ cells were macrophages. Results of our study suggest that T
      lymphocytes and/or macrophages play important roles in luteal regression and
      follicular atresia in normal-cycling human ovaries.

PMID- 9756295
TI  - Effect of smoking on ovarian reserve and ovarian stimulation in in-vitro
      fertilization and embryo transfer.
AB  - The effect of cigarette smoking on ovarian reserve as measured by basal serum
      follicle stimulating hormone (FSH) concentrations, and by the response to a
      standard ovarian stimulation protocol, was examined retrospectively in 173
      consecutive women (108 non-smokers and 65 smokers) undergoing in-vitro
      fertilization (IVF) and embryo transfer treatment. Women who smoked had a higher
      mean basal serum FSH concentration (P < or = 0.0001), in particular younger (<36
      years) women, and required a statistically significantly higher mean dosage of
      gonadotrophins for ovarian stimulation than the non-smokers (48.1 +/- 15.6 versus
      38.9 +/- 13.6 ampoules, 75 IU/ampoule; P < 0.0001). A lower mean number of
      oocytes was obtained in smokers than non-smokers (6.2 +/- 3.4 versus 11.1 +/-
      6.3, oocytes P < or = 0.0001) and the rate of abandoned cycles (18.5 versus 8.5%)
      and total fertilization failure (18.5 versus 8.5%) was higher. The clinical
      pregnancy rate per cycle in smokers was 16.9% versus 21.3% in non-smokers but
      this was not statistically significant. In conclusion, cigarette smoking in women
      appears to significantly reduce their ovarian reserve and lead to poor response
      to ovarian stimulation at an earlier age.

PMID- 9756296
TI  - Presence of transforming growth factor alpha and epidermal growth factor in human
      ovarian tissue and follicular fluid.
AB  - Intra-ovarian regulation of follicular maturation is modulated by various
      factors. Among these, growth factors are important local actors. We examined the
      immunohistochemical localization of transforming growth factor alpha (TGF-alpha),
      epidermal growth factor (EGF) and epidermal growth factor receptor (EGF-R) in 18
      human ovaries. The concentration of TGF-alpha and EGF in follicular fluid was
      measured by ELISA. TGF-alpha was detected in oocytes of primordial and early
      preantral follicles. Furthermore, staining was observed in granulosa cells of
      preantral follicles and in theca cells of preantral, antral and preovulatory
      follicles. EGF showed a similar distribution as TGF-alpha. Atretic follicles were
      strongly positive for TGF-alpha and EGF. In the corpus luteum, theca lutein cells
      were strongly positive for TGF-alpha and EGF. Immunoreactivity for EGF-R was
      observed only in the granulosa cells of antral follicles. Follicular fluids from
      patients undergoing in-vitro fertilization (IVF) were examined for their content
      of TGF-alpha and EGF. TGF-alpha was detected in 37% of the samples. The
      concentration ranged from 43 pg/ml to 602 pg/ml. EGF was not detected in any of
      the follicular fluids tested. These observations support the participation of
      EGF/TGF-alpha in follicular maturation. Furthermore, the presence of TGF-alpha in
      follicular fluid and the simultaneous absence of EGF suggests that TGF-alpha
      plays a more pronounced role than EGF in oocyte maturation during late follicular
      phase.

PMID- 9756297
TI  - Expression of interleukin-1 system mRNA in single blastomeres from human
      preimplantation embryos.
AB  - Gathering knowledge about the molecular events during preimplantation development
      is one of the most important challenges in in-vitro fertilization (IVF). The
      interleukin-1 (IL-1) system has been shown to be intimately involved in embryonic
      implantation. The aim of our study was to detect the major components of the IL-1
      system in single blastomeres from human preimplantation embryos and to relate our
      findings to the further development of the biopsied embryos in vitro. Single
      blastomeres were removed from morphologically normal embryos obtained from
      dipronuclear zygotes and examined by reverse transcription (RT)-nested polymerase
      chain reaction (PCR). Expression of beta-actin (external standard), IL-1beta, IL
      1 receptor antagonist (IL-1ra) and IL-1 receptor (IL-1R) type I mRNA were related
      to embryonic development and IVF outcome. Blastomeres from 12 embryos were
      examined: beta-actin and IL-1R type I mRNA were detected in all blastomeres
      (100%) whereas IL-1beta could be detected in only nine of the blastomeres (75%).
      IL-1ra was expressed in only two (17%) of the blastomeres and those were
      simultaneously positive for IL-1beta. Both IL-1ra positive embryos were arrested
      in development before reaching blastocyst stage. Five embryos (three of them IL
      1beta mRNA positive and two IL-1beta mRNA negative) were transferred as
      blastocysts; none of the transfers resulted in a pregnancy. We postulate that
      embryos expressing IL-1ra mRNA in a detectable amount appear more likely to be
      arrested in early developmental stages.

PMID- 9756298
TI  - Implications of complete fertilization failure after intracytoplasmic sperm
      injection for subsequent fertilization and reproductive outcome.
AB  - With the introduction of intracytoplasmic sperm injection (ICSI), couples with
      severe male factor infertility have achieved fertilization and clinical pregnancy
      rates comparable to other in-vitro fertilization (IVF) patients. However, failure
      of fertilization still occurs in some patients despite the utilization of
      microsurgical sperm injection techniques. How such fertilization failure after
      ICSI might impact later ICSI treatment(s) is unknown. In this investigation,
      couples with complete fertilization failure after ICSI treated from August 1993
      to August 1996 were identified (index cycle, n = 21). Additionally, fertilization
      data from any previous or subsequent infertility treatments were evaluated. Seven
      patients (33%) had at least one IVF treatment before the index cycle, although no
      deliveries occurred. Of patients with complete fertilization failure in the index
      cycle, 48% (n = 10) underwent at least one subsequent ICSI cycle which proceeded
      to oocyte retrieval. The remainder (n = 11) elected to discontinue treatment.
      Although six subsequent cycles were cancelled due to poor follicular response (<
      or = 2 mature oocytes), all patients electing to continue treatment eventually
      achieved a subsequent embryo transfer. The clinical pregnancy rate per transfer
      was 45.4% for this group; the delivery and ongoing pregnancy rate per transfer
      was 36.3%. Review of semen parameters, superovulation characteristics or other
      clinical parameters during the three study cycles (pre-index, index, and post
      index) was not prognostic of fertilization success or reproductive outcomes in
      later treatments. Fertilization failure with ICSI therefore could not be
      predicted by prior cycle performance, although total immotility of spermatozoa at
      time of oocyte retrieval, total teratozoospermia, and low oocyte yield were
      common characteristics of couples experiencing complete fertilization failure
      with ICSI. These findings suggest that fertilization failure in one ICSI cycle
      does not preclude successful fertilization and delivery in a later ICSI
      treatment.

PMID- 9756299
TI  - Microtubule and microfilament organization in maturing human oocytes.
AB  - Various stages of immature human oocytes were imaged for microtubule,
      microfilament and chromatin organization. After germinal vesicle breakdown, a
      small microtubule aster was observed near the condensed chromatin. The asters
      appeared to elongate and encompass the condensed chromatin. At metaphase I stage,
      microtubules were detected in the meiotic spindle. The meiotic spindle in
      metaphase II was a symmetric, barrel-shaped structure containing anastral broad
      poles, located peripherally and radially oriented. After germinal vesicle
      breakdown, treatment with taxol induced numerous cytoplasmic foci of
      microtubules, mainly in the cortex of the oocyte. Microfilaments were observed as
      a relatively thick uniform area around the cell cortex and were also found near
      the germinal vesicle position. After germinal vesicle breakdown, the
      microfilaments were seen in both the cortex and around the female chromatin. In
      conclusion, this study suggests that both microtubules and microfilaments are
      closely associated with the reconstruction and proper positioning of chromatin
      after germinal vesicle breakdown and during meiotic maturation in human oocytes.

PMID- 9756300
TI  - Influence of oocyte preincubation time on fertilization after intracytoplasmic
      sperm injection.
AB  - During the intracytoplasmic sperm injection (ICSI) procedure, the collected
      oocytes are incubated until just before ICSI. The ideal preincubation time of
      oocytes was investigated in 544 treatment cycles. Oocyte retrieval was carried
      out 35 h after human chorionic gonadotrophin administration. Oocytes were
      cultured for between 1 and 11 h before ICSI. Embryo transfer was performed 48 h
      after oocyte collection. The survival, fertilization and cleavage rates of
      injected oocytes indicated no statistically significant differences between
      oocytes preincubated for different lengths of time. The proportion of good
      quality embryos (grades 1 and 2) was lower at 9-11 h of preincubation time than
      for all the other preincubation times (P < 0.001). No statistically significant
      differences were detected in the pregnancy rate between each group (mean: 15.9%),
      although the pregnancy rate at 9-11 h of preincubation time appeared to be low
      (7.7%). These results suggest that the oocyte retained sufficient potential for
      fertilization between 1 and 9 h after oocyte collection in ICSI. For the
      researchers who practise more complex ICSI procedures than IVF, it would be
      convenient to be able to perform ICSI at any time between 1 and 9 h after oocyte
      collection.

PMID- 9756301
TI  - Fatty acid composition of fertilization-failed human oocytes.
AB  - The aim of the study was to assess the fatty acid composition of human
      fertilization-failed oocytes. A total of 150 unfertilized oocytes from 43 women
      undergoing in-vitro fertilization (IVF) were analysed using capillary gas
      chromatography. The majority of fatty acids were saturated (79.22%), of which
      stearic (38.65%) and palmitic (32.66%) acids were the most abundant. Of the
      monounsaturated fatty acids (14.27%) oleic acid was the most abundant (9.77%).
      Polyunsaturated fatty acids comprised 6.50% of fatty acids, the n-6:n-3 ratio
      being 7.73. The ratio of eicosapentaenoic acid:docosahexaenoic acid was
      approximately 5. It is concluded that the most common fatty acids in human
      unfertilized oocytes are either saturated or monounsaturated fatty acids, whose
      main function is to provide an energy source. A number of differences in fatty
      acid composition were observed, in comparison with other biological samples. In
      particular, stearic and eicosapentaenoic acids were more prominent, and oleic and
      linoleic acids were less prominent; this may reflect some specific peculiarity of
      oocyte metabolism.

PMID- 9756302
TI  - Monoclonal antibodies against epidermal growth factor prevent outgrowth of mouse
      embryos in vitro.
AB  - The necessity of epidermal growth factor (EGF) in the process of mouse embryo
      development and outgrowth in vitro was studied. Mouse 4-cell stage embryos were
      cultured up to spreading stage (outgrowth) in human tubal fluid (HTF) medium
      alone (control) or with 10 ng/ml EGF and 1:250 diluted monoclonal antibodies
      against EGF (study groups). Hatching and outgrowth were significantly increased
      up to 60.9 and 52.4% respectively, while in the control only 33.7 and 20.4%
      reached hatching and outgrowth respectively. Moreover monoclonal antibodies
      against EGF significantly inhibited embryo development (P < 0.01). Only 5.8% of
      the embryos reached the hatching stage and none of them reached the spreading
      stage. Our results show that EGF is probably involved in the modulation of early
      embryonic growth and in the initiation of implantation.

PMID- 9756303
TI  - Ultrasound covers and sonographic gels are embryo-toxic and could be replaced by
      non-toxic polyethylene bags and paraffin oil.
AB  - The objective of this study was to test the hypothesis that ultrasound covers and
      sonographic gels, used during vaginal ultrasound, are toxic for mouse embryonic
      development in vitro. A prospective randomized design was used on pronucleate ova
      of F1 hybrid CBA x C57Bl female mice. The mice were superovulated with pregnant
      mare's serum gonadotrophin and human chorionic gonadotrophin and mated with CBA x
      C57Bl males. The pronucleate ova were randomly divided between culture media with
      the addition of commercially available ultrasound covers and sonographic gels in
      different concentrations. As controls and potential alternatives, plastic
      polyethylene bags and paraffin oil were tested simultaneously. Embryo-toxicity
      was assessed by documenting cleavage capacity, blastocyst formation and embryo
      degeneration in vitro. Exposure of culture medium to the ultrasound covers and
      sonographic gels tested resulted in a severely reduced cleavage capacity, a high
      incidence of embryo degeneration and absent or impaired blastocyst formation.
      This toxic effect could be reduced by high dilutions in vitro. In contrast,
      plastic polyethylene bags and paraffin oil had no influence on in-vitro
      development of mouse ova. We conclude that commercially available ultrasound
      latex covers and sonographic gels are toxic for mouse embryos and can potentially
      influence embryonic development during infertility treatment. It is safer to
      perform vaginal ultrasonic measurements using non-toxic paraffin oil (as contact
      fluid) and plastic polyethylene bags (as ultrasonic cover).

PMID- 9756304
TI  - Preimplantation genetic diagnosis principles and ethics.
AB  - Preimplantation genetic diagnosis (PGD) followed by implantation of unaffected
      embryos offers high-risk couples the option to decrease the risk of genetic
      disease in their offspring without the dilemma of a prenatal diagnosis that may
      be followed by a termination of pregnancy. Polar body, blastomere and blastocyst
      biopsies are currently being performed, whereas the two major technologies used
      for single-cell genetic analysis involve the polymerase chain reaction and
      fluorescence in-situ hybridization. PGD, similar to other prenatal diagnosis
      methods, raises many ethical and legal dilemmas. The high cost of practice and
      the low pregnancy rate achieved are still considered the major drawbacks of this
      new procedure.

PMID- 9756305
TI  - Expression of class I human leukocyte antigen (HLA) and beta2-microglobulin is
      associated with decidualization of human endometrial stromal cells.
AB  - Human leukocyte antigen (HLA) class I molecules play a central role in the immune
      system through either presentation of endogenous antigen and activation of T
      lymphocytes or functional emergence of natural killer (NK) cells. Various types
      of immune cells are present in the human endometrium and are believed to be
      involved in reproductive function and/or immunological reaction. However, little
      is known about the expression status and function of HLA class I molecules in the
      human endometrium. We therefore examined mRNA expression of HLA class I. In
      addition, we analysed gene expression and localization of beta2-microglobulin
      (beta2-MG), which is the non-variant chain of all HLA class I molecules. Compared
      with non-decidualized tissues, mRNA expression of both HLA class I and beta2-MG
      was significantly higher in decidualized endometria in the late secretory phase,
      under progestin treatment and during early pregnancy. Immunohistochemical studies
      revealed that beta2-MG was localized in decidualized endometrial stromal cells,
      indicating that the distribution of beta2-MG is topologically correlated with
      that of CD56bright+ NK cells. In-vitro culture of human endometrial stromal cells
      demonstrated that HLA class I mRNA was induced during the decidualization by
      progesterone. Accordingly, the expression of HLA class I molecules is
      transcriptionally activated along with decidualization of human endometrial
      stromal cells, and may represent an immuno-endocrine function of the endometrium.

PMID- 9756306
TI  - Relationship of the menstrual cycle pattern in 14-17 year old old adolescents
      with gynaecological age, body mass index and historical parameters.
AB  - In a cross-sectional population-based study the association between the menstrual
      pattern in ninth grade schoolgirls and calendar age, gynaecological age, body
      mass index (BMI) and historical parameters was investigated. The survey was held
      in a combined urban and rural region, south of Amsterdam. A total of 2480
      adolescents, mean age 15.3 +/- 0.6 (SD) years, answered a questionnaire: response
      92%. The menstrual cycle patterns were categorized to regular menstrual cycles
      (RMC), irregular menstrual cycles (IMC), oligomenorrhoea, polymenorrhoea, pre
      menarche, <6 months after menarche, and oral contraceptive use. Gynaecological
      age was strongly associated with the prevalence of IMC but only weakly with the
      prevalence of oligomenorrhoea. In a logistic regression analysis gynaecological
      age, subjective acne and intellectual performance were independently associated
      with oligomenorrhoea. Gynaecological age, low BMI, chronic non-specific lung
      disease (CNSLD) or allergic disease, stress and strain, weight loss of >5 kg were
      independently associated with IMC. More than 8 h sports per week was associated
      with not having experienced menarche in the ninth grade but not with menstrual
      cycle disturbances. The association between CNSLD or allergic disease and IMC has
      not previously been described. The associations between weight loss, low body
      weight, stress, physical exercise or signs of hyperandrogenism and menstrual
      cycle patterns in adolescents are weak when studied on a population basis. The
      value of these parameters to explain abnormal menstrual cycle patterns is
      limited.

PMID- 9756307
TI  - A prospective randomized controlled study comparing the morphological and
      biochemical responses of the endometrium to two different forms of 'period-free'
      hormone replacement therapy.
AB  - Thirty postmenopausal women were randomized to receive either continuous combined
      (cc) 2 mg oestradiol valerate and 0.7 mg norethisterone acetate hormone
      replacement therapy (HRT) daily (15 women) or tibolone 2.5 mg daily (15 women)
      and were monitored to determine the relationship between the two biochemical
      markers placental protein 14 (PP14) and the glycoprotein CA125, endometrial
      histology and occurrence of irregular bleeding after 12 months of treatment. The
      concentrations of PP14 and CA125 in plasma and uterine flushings before and after
      therapy were measured and their concentrations were associated with the histology
      of endometrial biopsies obtained on the same day as venesection and endometrial
      flushing. The levels of PP14 in uterine flushings were significantly increased
      after the administration of both types of HRT (P < 0.05 for tibolone and P <
      0.001 for ccHRT). However, the concentrations of PP14 found in flushings after
      ccHRT were considerably greater than those found in flushings after tibolone;
      levels were increased about 150-fold by ccHRT and 6-fold by tibolone (P < 0.001).
      Plasma concentration of PP14 after both types of HRT were also significantly
      raised to a similar degree (P < 0.01). In contrast, the concentration of plasma
      and uterine CA125 were unchanged by either treatment. Histological analysis of
      the endometrium from women after 12 months of HRT treatment showed that 86% (6/7)
      of women on ccHRT had secretory activity as compared to 44% (4/9) women on
      tibolone (P < 0.05). Women with higher post-HRT uterine PP14 concentration were
      more likely to have irregular bleeding (P < 0.05). Our studies have shown that
      endometrial PP14 but not CA125 concentrations are raised to a significant degree
      by two different forms of period-free HRT regimens. Increased PP14 concentrations
      in uterine flushing may suggest endometrial stimulation of some form and predict
      the predilection to irregular bleeding. Thus uterine PP14 concentrations may be
      used to monitor endometrial responses in women on HRT.

PMID- 9756308
TI  - Results and role of rectal endoscopic ultrasonography for patients with deep
      pelvic endometriosis.
AB  - The objective of this work was to assess the advantages and the role of rectal
      endoscopic ultrasonography (EUS) when establishing evidence of infiltration of
      the rectal wall in patients with proven deep pelvic endometriosis. To this end we
      performed a retrospective study between July 1993 and December 1996 of a
      continuous series of 38 patients who presented with deep pelvic endometriosis
      which was confirmed histologically. The EUS results were considered normal in
      nine cases (23.7%). In 12 cases (31.6%) EUS revealed an image compatible with
      infiltration of the uterosacral ligaments and/or the rectovaginal septum without
      any associated bowel infiltration. In 17 cases (44.7%) EUS revealed an image
      compatible with deep infiltration of the intestinal wall. Sixteen of these 17
      patients underwent laparotomy with bowel resection. The histological results
      confirmed in each of these 16 patients (100%) that there was deep infiltration of
      the intestinal wall by endometriotic lesions. The seventeenth patient refused
      such major surgery by laparotomy, and underwent partial laparoscopy due to the
      risk of bowel injury. For the 21 patients with no EUS evidence of rectal
      infiltration complete laparoscopic surgical exeresis was achieved in every case
      (100%) without broaching the intestinal wall. These preliminary results enable us
      to state that EUS, which is a simple and non-invasive technique, provides a
      reliable indication as to the presence of deep bowel infiltration in patients
      with retroperitoneal endometriotic lesions. EUS used pre-operatively enables
      patients to be selected for treatment via laparotomy or by laparoscopic surgery.

PMID- 9756309
TI  - Surgical treatment of recurrent endometriosis: laparotomy versus laparoscopy.
AB  - The objective of this study was to clarify which is the better surgical
      conservative treatment for recurrent endometriosis. We compared two consecutive
      surgical series at a tertiary care centre for the cure of endometriosis. The
      patients were 81 women with recurrent endometriosis, 41 reoperated at laparotomy
      from 1986 to 1991 and 40 reoperated at laparoscopy from 1992 to 1996. Follow-up
      after the second operation included clinical and ultrasound examinations
      performed at least once a year to evaluate the recovery of fertility and the
      reappearance of symptoms and signs of the disease. The cumulative probability of
      recurrence of dysmenorrhoea (34 and 43 respectively), and the frequency of
      recurrence of pelvic pain and dyspareunia and of clinical findings suggestive of
      the disease were not significantly different in the two groups. The rate of
      recurrence of dyspareunia was higher in the patients operated at laparotomy as
      was the number requiring a third operation. However, this could be due to the
      longer follow-up of this group. No significant difference was observed between
      the cumulative pregnancy rates at 24 months in the two groups (45 in the
      laparotomy and 54 in the laparoscopy group). We conclude that operative
      laparoscopy seems as efficacious as conservative surgery at laparotomy in the
      treatment of recurrent endometriosis.

PMID- 9756310
TI  - Adhesion of human endometrium to the epithelial lining and extracellular matrix
      of amnion in vitro: an electron microscopic study.
AB  - One of the first steps in the pathogenesis of endometriosis is the attachment of
      the endometrium to the peritoneal lining. Since the peritoneum is extremely
      fragile and hard to obtain, amnion has been used as an in-vitro model to study
      adhesion. Scanning and transmission electron microscopy was applied to evaluate
      the adhesion of endometrial cells isolated in the proliferative and secretory
      phases of the menstrual cycle. Endometrial fragments obtained in either phase of
      the cycle were able to adhere to the extracellular matrix of the amnion.
      Fragments from proliferative phase endometrium showed active spreading and growth
      over the matrix surface, whereas fragments from secretory phase endometrium did
      not. Fragments from proliferative as well as secretory phase endometrium were
      able to adhere to the epithelial side of the amnion, but only at locations where
      the amniotic epithelium was damaged or partly absent. These observations indicate
      that the basement membrane and extracellular matrix provide a suitable substrate
      for endometrial cell attachment and growth and that endometrial cell adhesion
      occurs preferentially to subepithelial structures, whereas an intact epithelium
      prevents the adhesion of endometrial fragments to the amnion.

PMID- 9756311
TI  - The effect of dexamethasone administration at different stages of gestation on
      maternal plasma steroid concentrations in the baboon (Papio cynocephalus).
AB  - Dexamethasone administration at different stages of gestation in the baboon was
      studied for its effect on maternal steroid hormone concentrations. Dexamethasone
      (2 mg i.m. at 12 h intervals for three doses) was administered at early (days 37
      39), mid (days 76-85) or late (days 112-123) gestation and morning blood samples
      were collected before, during and after dexamethasone suppression for 6
      consecutive days. Dexamethasone treatment, at all stages of pregnancy, resulted
      in a significant decline in maternal serum cortisol concentrations, which rapidly
      return to normal concentrations after treatment. Progesterone concentrations were
      not affected by dexamethasone at any stage of gestation. Serum concentrations of
      oestradiol, testosterone and androstenedione were unchanged following
      dexamethasone administration in early pregnancy. A trend toward lower serum
      oestradiol was observed following dexamethasone administration in both mid and
      late gestation, but this was not significant. Both testosterone and
      androstenedione were significantly decreased following dexamethasone in both mid
      and late pregnancy and recovered to pretreatment concentrations within a few days
      after cessation of treatment. These results confirm other studies which
      demonstrate that adrenal precursors (maternal or fetal) are a major contributor
      to maternal serum concentrations of oestradiol. They also demonstrate that these
      adrenal precursors increase serum concentrations of testosterone and
      androstenedione in the pregnant baboon. Since these changes are only evident
      after that time (>40 days) when the fetal adrenal is steroidogenically competent,
      a role for fetal adrenal involvement in maternal serum androgen concentrations is
      suggested.

PMID- 9756312
TI  - Coffee consumption and risk of hospitalized miscarriage before 12 weeks of
      gestation.
AB  - In order to analyse the association between drinking coffee in pregnancy and risk
      of spontaneous abortion, a case-controlled study was conducted in Milan, Northern
      Italy. Cases were 782 women with spontaneous abortion within the 12th week of
      gestation. The control group was recruited from women who gave birth at term (>
      37 weeks gestation) to healthy infants on randomly selected days at the same
      hospitals where cases had been identified: 1543 controls were interviewed. A
      total of 561 (72%) cases of spontaneous abortion and 877 (57%) controls reported
      coffee drinking during the first trimester of the index pregnancy. The
      corresponding multivariate odds ratios of spontaneous abortion, in comparison
      with non-drinkers, were 1.2, 1.8 and 4.0, respectively, for drinkers of 1, 2 or
      3, and 4 or more cups of coffee per day. No relationship emerged between maternal
      decaffeinated coffee, tea and cola drinking in pregnancy, as well as paternal
      coffee consumption, and risk of spontaneous abortion. With regard to duration in
      years of coffee drinking, the estimated multivariate odds ratios of spontaneous
      abortion were, in comparison with non-coffee drinkers, 1.1 (95% confidence
      interval (CI) 0.9-1.4) and 1.9 (95% CI 1.5-2.6) for women reporting a duration of
      coffee consumption < or = 10 or > 10 years. In conclusion, coffee drinking early
      in pregnancy was associated with an increased risk of abortion. This has
      biological implications, but epidemiological inference on the causality is
      difficult and still open to debate.

PMID- 9756313
TI  - Differential concentrations of monocyte chemotactic protein-1 and interleukin-8
      within the fluid compartments present during the first trimester of pregnancy.
AB  - Monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) are important
      chemokines which effect the chemotaxis of monocytes and neutrophils,
      respectively. There is increasing evidence that such chemokines play an integral
      role in the control and maintenance of a normal pregnancy from implantation to
      parturition. However, little is known about the sites of secretion and function
      of MCP-1 and IL-8 in particular with respect to establishment of the placenta and
      membranes during first trimester. The aim of this study was therefore to
      investigate the concentrations and localization of MCP-1 and IL-8 in amniotic
      fluid and extra-embryonic coelomic fluid (EECF) collected by ultrasound-guided
      needle aspiration and maternal serum during the first trimester of pregnancy.
      Using specific enzyme-linked immunosorbent assays, MCP-1 was present at high
      concentrations in the EECF, significantly higher than those in amniotic fluid and
      maternal serum. IL-8 was also present predominantly in the EECF with
      concentrations being significantly higher than the low values detected in
      maternal serum and the very low amounts found in amniotic fluid. This strict
      compartmentalization of these cytokines in the fluid compartments of early
      pregnancy may be important for establishment and development of a viable
      pregnancy.

PMID- 9756314
TI  - Stress and anxiety do not result in pregnancy wastage.
AB  - The association between stress and reproductive outcome is unclear. In-vitro
      fertilization (IVF) is psychologically stressful and has been shown to alter
      psychological markers such as cortisol, prolactin and progesterone. This study
      was designed to assess prospectively psychological and physiological markers of
      stress and to determine if they are related to pregnancy outcome. Forty patients
      were recruited from Northwestern Medical Faculty Foundation (Chicago, Illinois,
      USA) having obtained an initial positive beta-human chorionic gonadotrophin (HCG)
      concentration 13 days after IVF with uterine embryo transfer. Patients underwent
      psychological and hormonal testing on three separate occasions (13, 20 and 27
      days after embryo transfer) early in pregnancy. All subjects were followed to
      delivery. An adverse outcome was defined as a miscarriage before or after cardiac
      activity (including vanishing twin) or a loss before 20 weeks gestation. There
      was no difference in age, duration of infertility, diagnosis between patients
      experiencing an adverse pregnancy outcome (n = 18) and those that did not (n =
      22). All patients were found to have high stress levels although this did not
      differentiate between groups of patients. There was no difference in hormonal
      markers of stress between patients. In conclusion, there is little association
      between psychological scores and physiological stress hormone concentrations.
      Also, it does not appear that high levels of anxiety and stress result in an
      adverse pregnancy outcome.

PMID- 9756315
TI  - Selective termination and elective reduction in twin pregnancies: 10 years
      experience at a single centre.
AB  - Selective termination is employed in multifetal pregnancies, in the presence of
      an abnormal fetus, in order to improve the prognosis of the normal fetuses. The
      term elective reduction is used to describe reduction in twin pregnancies for
      maternal medical conditions, psychological, or socioeconomic reasons. The purpose
      of this study was to evaluate the factors that influence outcome in such
      pregnancies. Eighty-two twin pregnancies underwent selective termination (n = 59)
      or elective reduction (n = 23) over a 10-year period. Early procedures, performed
      < or = 14 weeks (n = 31), had a pregnancy loss of 9.7% and a mean procedure-to
      loss interval of 4.1 +/- 2.8 weeks; mean birthweight was 3299 +/- 395 g in
      survivors, with a mean gestational age at delivery of 38.4 +/- 2.3 weeks. In
      comparison, procedures performed > 14 weeks (n = 51) had a pregnancy loss of
      7.8%, with a procedure-to-loss interval of 1.2 +/- 0.6 weeks. Mean birthweight
      was 2577 +/- 999 g, with a mean gestational age at delivery of 35.7 +/- 5 weeks.
      In conclusion, outcomes were more favourable among patients who underwent a first
      trimester procedure. The slight increase in pregnancy loss may be attributed to a
      higher than expected rate of spontaneous abortions in the first trimester, as
      manifested by the higher procedure-to-loss interval after a first trimester
      procedure. These facts underscore the importance of early detection of fetal
      abnormalities in twin pregnancies by ultrasonography and chorionic villus
      sampling.

PMID- 9756316
TI  - Evaluation of serum inhibin A as a surveillance marker after conservative
      management of tubal pregnancy.
AB  - Tubal pregnancy is now commonly managed by laparoscopic salpingostomy or systemic
      methotrexate. A disadvantage of such conservative management is the need for
      appropriate follow-up, with serial measurement of serum concentrations of human
      chorionic gonadotrophin (HCG), to exclude persistent ectopic pregnancy (PEP).
      Concentrations of inhibin A, also a placental product, are significantly
      increased during pregnancy and the half-life of inhibin A is significantly
      shorter than that of HCG. To assess the suitability of inhibin A as a marker of
      PEP, we studied 16 women who had undergone surgery for a tubal pregnancy,
      measuring HCG and inhibin during follow-up. The mean +/- SEM time taken to
      achieve non-pregnant concentrations of inhibin A was significantly shorter than
      for HCG (4.2 +/- 0.8 days versus 21.6 +/- 4.4 days respectively; P < 0.001
      Wilcoxon signed rank test). However, in all women the inhibin A concentration
      increased rapidly after reaching a nadir, reflecting the return of ovarian
      function, complicating the interpretation of results. In four women inhibin A was
      almost undetectable preoperatively, while the corresponding HCG concentration was
      high. These data suggest that inhibin A will not be a useful marker for PEP but
      that it may provide a more accurate preoperative assessment of trophoblast
      viability than HCG, thereby improving management.

PMID- 9756317
TI  - Shedding of tumour necrosis factor receptors from purified villous term
      trophoblasts and cytotrophoblastic BeWo cells.
AB  - Within the placenta tumour necrosis factor-alpha (TNF-alpha) and its surface
      receptors TNF-RI and -RII have been detected on villous cyto- and
      syncytiotrophoblast and a role in trophoblast function/differentiation and
      turnover has been suggested. Here, we show for the first time that purified
      villous trophoblasts and cytotrophoblastic BeWo cells extensively shed TNF
      receptors, suggesting that release of these soluble proteins is an inherent
      property of trophoblasts. In supernatants of purified villous trophoblasts, TNF
      RI and -RII increased from undetectable levels to 307 pg/ml and 484 pg/ml,
      respectively, within 12 h of cultivation. In BeWo cells, 26 pg/10(5) cells and 54
      pg/10(5) cells of soluble TNF-RI and -RII, respectively, accumulated within 24 h
      of culturing. While forskolin did not alter TNF-RI expression, TNF-RII mRNA,
      protein and secretion were selectively up-regulated in these choriocarcinoma
      cells suggesting that elevation of cAMP levels could modulate cellular events by
      TNF-RII-mediated signal transduction. Interleukin-1, which greatly enhances TNF
      alpha release from trophoblast cells, did not alter shedding of both receptors
      from villous trophoblasts or BeWo cells. Secretion of TNF receptors from the
      trophoblast may explain the high levels of soluble TNF-binding proteins in urine
      of pregnant women and could play a role in regulating TNF-alpha activity in the
      placental villus or protection against the cytotoxic effects of the cytokine.

PMID- 9756318
TI  - Placental transfer of fentanyl in early human pregnancy.
AB  - To investigate the transfer of fentanyl across the early human placenta, we have
      collected samples of maternal blood and fetal fluids and/or blood,
      simultaneously, between 5 and 22 min following an intravenous bolus of fentanyl
      (1.5 microg/kg) to the mother. The pregnancies were between 6 and 16 weeks of
      gestation and scheduled for elective termination of pregnancy under general
      anaesthesia. Total fentanyl concentration was determined by radioimmunoassay in
      11 pairs of first trimester maternal serum and fetal coelomic fluid samples, 14
      pairs of maternal serum and amniotic fluid samples, seven series of first
      trimester maternal serum and coelomic and amniotic fluid samples, and 10 series
      of early second trimester maternal and fetal sera and amniotic fluid samples.
      Fentanyl was not detected in coelomic fluid samples at any gestational age and in
      amniotic fluid samples collected after 12 weeks of gestation. Measurable
      concentrations of fentanyl were found in maternal serum collected within 15 min
      after the initial bolus and in fetal serum collected between 10 and 12 min later.
      These findings indicate that fentanyl is transferred across the early placenta
      into the amniotic cavity and fetal blood circulation but not into the exocoelomic
      cavity. The distribution of this molecule inside the early gestational sac is
      probably influenced by the increased binding by maternal and fetal sera, its
      short half-life of distribution and the specific biology of the fetal fluid
      formation and composition.

PMID- 9756320
TI  - Male to female ratio in newborns of grand grand multiparous women.
AB  - The male to female ratio in newborns of grand grand multiparous women was
      evaluated in 569 Jewish Orthodox women and 28 Muslim women. A total of 882 babies
      was born on the > or = 10th delivery; 460 (52.2%) were males and 422 (47.8%) were
      females (sex ratio = 1.06). Newborn sex ratio did not significantly change with
      respect to birth order or maternal age. It is suggested that parity and
      increasing maternal age do not affect the sex ratio of newborns and that ethnic
      and environmental variables may play a role in the deviations in offspring sex
      ratio observed among different populations.

PMID- 9756319
TI  - Decline in sex ratio at birth after Kobe earthquake.
AB  - We investigated the possible association between the Kobe earthquake (January
      1995) and the sex ratio among live-born infants after the catastrophe. A
      significant decline in the sex ratio (0.501) of Hyogo Prefecture in October 1995
      was observed 9 months after the Kobe earthquake as compared with an expected
      value of 0.516 in the period from January 1993 to January 1996 (P = 0.04; one
      tailed). Simultaneously, a reduction in fertility of approximately 6% was also
      observed, compared with the month of October 2 years previously. Thus, the acute
      stress resulting from a great natural catastrophe can be a cause of a low sex
      ratio at birth 9 months later.

PMID- 9756321
TI  - Hormones and cardiovascular diseases: oral contraceptives and hormonal
      replacement therapy: differential effects on coronary heart disease, deep venous
      thrombosis and stroke. The ESHRE Capri Workshop Group.

PMID- 9756322
TI  - Motile organisms in the epididymis?

PMID- 9756324
TI  - Secular movements in dizygotic twinning rates and in sperm counts.

PMID- 9756325
TI  - Biased postural vertical in humans with hemispheric cerebral lesions.
AB  - This study was aimed at demonstrating the existence of a biased postural vertical
      in humans with a recent cerebral lesion. The postural vertical of patients and
      controls was analysed comparatively using a self-regulated balancing task,
      performed in sitting posture. Patients displayed a quite constant (19/22)
      contralesional tilt of the postural vertical (mean -2.6 degrees), varying with
      the severity of their spatial neglect and hemianaethesia. Eight of them showed a
      pathological contralesional bias (mean -5.5 degrees) as compared to normals. This
      result indicates an asymmetric process of somatic graviceptive information due to
      some cerebral lesions. When patients were subjected to a transcutaneous
      electrical stimulation applied onto the contralesional side of the neck, body
      verticality was especially improved in those who showed a pathological bias in
      the postural vertical. This effect could thus be due to a reduced distortion in
      the egocentric co-ordinate system for spatial information processing.

PMID- 9756326
TI  - Modality-specific subregions in human inferior parietal lobule: a
      magnetoencephalographic study during cognitive tasks.
AB  - The inferior parietal lobule (IPL) has been considered to be a multimodal sensory
      association area. Both event-related potentials and magnetic responses have
      examined the relationships between IPL and cognitive processing. However, there
      have been no studies clarifying the functional subregions in IPL. We studied the
      event-related magnetic response during conventional auditory and visual oddball
      paradigms. We were able to distinguish non-invasively modality-specific
      subregions in IPL. The subregion in IPL activated by auditory target stimuli was
      located more anterior and superior than that responding to visual target stimuli
      on each hemisphere. The data suggests that modality-specific subregions in the
      IPL are differentially activated by auditory or visual stimuli.

PMID- 9756327
TI  - Cholinergic lesions of the rat brain by ibotenic acid and 192 IgG-saporin:
      effects on somatostatin, substance P and neuropeptide Y levels in the cerebral
      cortex and the hippocampus.
AB  - Impairment of the basal forebrain cholinergic system is an important change in
      the brains of Alzheimer's disease patients. Various neurotoxins have been used to
      achieve this in animal models. In this study the effects of chemical lesions by
      ibotenic acid (IBO), a glutamate analogue and by 192 IgG-saporin, a highly
      specific immunotoxin against cholinergic neurons, were investigated. The toxins
      were delivered stereotaxically into the brains of young Sprague-Dawley rats which
      were later sacrificed by decapitation. Choline acetyltransferase (ChAT) activity
      was measured by radioenzymatic assay and substance P (SP), neuropeptide Y (NPY)
      and somatostatin (SOM) levels by radioimmunoassay. Decreased ChAT and SOM levels
      were observed in the cortex and the hippocampus in both experiments. Cortical SP
      levels were increased after IBO lesions but were unaffected after 192 IgG-saporin
      lesions. NPY levels remained unchanged in both experiments. The results indicate
      that there were specific changes in neuropeptide contents in the cortex and
      hippocampus in response to cholinergic damage in the rat brain.

PMID- 9756329
TI  - Minimum light intensity required to suppress nocturnal melatonin concentration in
      human saliva.
AB  - We set out to determine the minimum intensity of light able to suppress nocturnal
      melatonin levels as measured in normal human saliva. Five healthy male volunteers
      were exposed to light at different intensities (<10, 500, 1000, 2500, and 5000
      lux) in a repeated measure design. Suppression of melatonin was dependent on both
      light intensity and duration of light exposure. Minimum intensities of light
      suppressing nocturnal melatonin levels were calculated as 393, 366, 339, and 285
      lux for exposure durations of 30, 60, 90, and 120 min, respectively. Minimum
      effective intensity and duration of light exposure showed a linear inverse
      relationship. These results suggest that less intensity of light than previously
      reported suffices to suppress melatonin in humans, and that caution is required
      in interpreting studies using long exposure to dim light as a background
      condition.

PMID- 9756328
TI  - Glial cell line-derived neurotrophic factor protects against 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in C57BL/6 mice.
AB  - To mimic chronic exposure to neurotoxins in inducing dopaminergic cell damage,
      multiple doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were
      injected in C57BL/6 mice. Effects of pre- and post-treatment with the glial cell
      line-derived neurotrophic factor (GDNF) by injections into the striatum were
      investigated. GDNF exerts protective and reverse effects on the dopaminergic
      damage, supporting the potential application of GDNF in prevention and treatment
      of Parkinson's disease.

PMID- 9756330
TI  - The -491A/T apolipoprotein E promoter polymorphism association with Alzheimer's
      disease: independent risk and linkage disequilibrium with the known APOE
      polymorphism.
AB  - The epsilon4 allele of the apolipoprotein E gene (APOE) has repeatedly been
      associated with increased risk for Alzheimer's disease (AD). Bullido and
      colleagues recently identified a polymorphism in the promoter region of the APOE
      gene (-491A/T) and found that -491A homozygosity predicted AD independently of
      APOE epsilon4. Since the -491A/T polymorphism and the known APOE polymorphism
      must be in tight linkage disequilibrium, and the later polymorphism is know to be
      associated with the disease, we wished to determine to what extent this linkage
      disequilibrium explained the -491A/T polymorphism association with Alzheimer's
      disease. We genotyped a community-based control sample (n = 132) and a clinic
      based Alzheimer's disease sample (n = 190) for the known APOE and -491A/T
      polymorphisms, and find that, while the -491A/T polymorphism confers some
      independent risk for AD, linkage disequilibrium between the known APOE and 
      491A/T polymorphic sites explains most of the -491A association. Furthermore,
      when considering the known APOE and -491A/T polymorphisms alone, APOE epsilon4
      status is the best predictor of the disease.

PMID- 9756331
TI  - Possible neural substrates of beer-craving in rats.
AB  - Rats voluntarily consumed beer in a distinctive environment during 30 min daily
      sessions over 21 days, ingesting a daily average of 0.96 g/kg of ethanol. On a
      final test day, rats in a 'craving' condition were denied access to the beer in
      the drinking environment. The expression of c-fos in the brain of 'craving' rats
      was compared with that in rats given free access on the test day ('beer'
      condition), and to rats which had been repeatedly placed in the drinking
      environment without ever having access to beer ('control' condition). Rats in the
      'craving' condition showed significantly higher c-fos counts than either the
      'beer' or 'control' rats in a variety of corticolimbic and brainstem structures,
      indicating that activation of these regions occurs when a desirable alcoholic
      beverage is expected but not received.

PMID- 9756332
TI  - Ciguatoxin (CTX-1) modulates single tetrodotoxin-sensitive sodium channels in rat
      parasympathetic neurones.
AB  - The actions of the marine neurotoxin, ciguatoxin-1 (CTX-1), were investigated in
      isolated parasympathetic neurones from neonatal rat intracardiac ganglia using
      patch-clamp recording techniques. Under current clamp conditions, bath
      application of 1-10 nM CTX-1 caused gradual membrane depolarization and tonic
      action potential firing. Action potential firing ceased with depolarization
      beyond approximately -35 mV and application of 300 nM tetrodotoxin (TTX)
      repolarized the cell to its control resting potential. In cell-attached membrane
      patches, 1-10 nM CTX-1 in the patch pipette markedly increased the open
      probability of single TTX-sensitive Na+ channels in response to depolarizing
      voltage steps but did not alter the unitary conductance (10 pS) or reversal
      potential. Under steady-state conditions, CTX-1 caused spontaneous opening of
      single Na+ channels which did not inactivate at hyperpolarized membrane
      potentials. CTX-1 increases neuronal excitability by shifting the voltage of
      activation of TTX-sensitive Na+ channels to more negative potentials.

PMID- 9756333
TI  - Glial cell line-derived neurotrophic factor and nerve growth factor receptor
      mRNAs are expressed in distinct subgroups of dorsal root ganglion neurons and are
      differentially regulated by peripheral axotomy in the rat.
AB  - We examined the colocalization of glial cell line-derived neurotrophic factor
      (GDNF) and nerve growth factor (NGF) receptor genes in rat dorsal root ganglion
      (DRG) neurons, and investigated the changes of the gene expression following
      sciatic nerve transection using in situ hybridization histochemistry. About 60%
      and 35% of the lumbar DRG neurons expressed c-ret and trkA, proto-oncogenes of
      the functional receptors for GDNF and NGF, respectively. Of the DRG neurons,
      however, only 9% was positive for both genes. A marked enhancement of the gene
      expression for GDNF receptor alpha (GDNFR alpha), which is a component of GDNF
      receptor, was observed in DRG neurons after sciatic nerve transection, but the
      percentage of c-ret mRNA-expressing neurons was not changed. The trkA mRNA
      expressing neurons were decreased in number. These findings suggest that GDNF and
      NGF support distinct subgroups in intact DRG neurons, and that these receptor
      genes are differentially regulated when a peripheral nerve is injured.

PMID- 9756334
TI  - Overexpression of glucose transporter protein 5 in sciatic nerve of
      streptozotocin-induced diabetic rats.
AB  - The localization and the expression level of glucose transporter 5 (GLUT 5),
      detected by immunohistochemical and Western blot analyses, and motor nerve
      conduction velocity (MNCV) in normal and streptozotocin (STZ)-induced diabetic
      rats were compared. The effects of insulin and recombinant human insulin-like
      growth factor-I (rhIGF-I) were also investigated. GLUT 5 was localized in Schwann
      cells and axons. GLUT 5 was overexpressed in both sites 5 weeks after STZ
      injection and MNCV was decreased significantly in STZ-induced diabetic rats as
      compared with normal rats. These deviations returned to normal rat level after 2
      weeks medication with insulin or rhIGF-I, started 3 weeks after STZ injection.
      These results suggest that overexpression of GLUT 5 may be a trigger for diabetic
      neuropathy.

PMID- 9756335
TI  - Right auditory cortex lesion in Mongolian gerbils impairs discrimination of
      rising and falling frequency-modulated tones.
AB  - Mongolian gerbils (Meriones unguiculatus) were trained in a shuttle box to
      discriminate the direction in frequency-modulated tones (FM). Whereas control
      animals easily acquired FM discrimination, animals with auditory cortex lesion on
      the right side showed considerable difficulties in learning this task. The
      discrimination performance of gerbils with left auditory cortex lesion, however,
      was not different from controls. This study, suggesting that the right auditory
      cortex plays a dominant role in FM discrimination learning in gerbils, describes
      a useful animal model for investigation of the basic mechanisms underlying
      hemispheric asymmetries in auditory perception.

PMID- 9756336
TI  - Induction of plasminogen in rat hippocampal pyramidal neurons by kainic acid.
AB  - Tissue plasminogen activator (tPA) is used to treat acute stroke, but tPA- and
      plasminogen-gene-deficient mice exhibit resistance to neurodegeneration. Thus, it
      is unclear whether the tPA-plasminogen system, an extracellular proteolytic
      cascade plays a helpful or harmful role, and whether plasminogen is induced by
      neurodegeneration. In the CA3, kainic acid (KA)-injection caused neuronal damage
      after 6 h, and almost all of the neurons were lost after 7 days. Plasminogen mRNA
      was strongly induced 6 h after injection, then gradually decreased, and was very
      weak at 2 days after injection. Plasminogen protein was expressed after 6 h and
      localized in abnormally shaped neurons. The in vivo expression of plasminogen was
      synchronous with morphological changes in neurons. These results suggest that the
      expression of plasminogen induced by KA-injection may disrupt of neuron
      extracellular matrix interaction and thereby contribute to cell death in neurons
      in the hippocampus.

PMID- 9756337
TI  - Dystrophin deficient myotubes undergo apoptosis in mouse primary muscle cell
      culture after DNA damage.
AB  - Apoptosis has been demonstrated to occur in differentiated myocardial muscle,
      neonatal skeletal muscle and skeletal myoblasts in response to injury. In this
      report, we studied differentiated normal and dystrophin deficient murine skeletal
      muscle cell cultures that have been injured by a pulse of cis-platinum (2 h).
      Forty-eight hours after DNA damage, dystrophin positive myotubes appeared almost
      normal though some myoblasts showed DNA fragmentation. On the other hand,
      dystrophin deficient myotubes presented progressive degeneration via apoptosis
      detected either by TUNEL or by nuclear morphology. Degeneration of mdx muscle
      fibers was confirmed by counting both the number of myotubes observed by contrast
      phase microscopy and myonuclei viewed by immunoreaction for MyoD. A 6-fold
      decrease in the number of muscle cells was observed in the dystrophin-deficient
      cell culture compared to the parental culture (P < 0.001). Direct evidence of
      degenerating myotubes displaying MyoD- and TUNEL-positive nuclei was obtained.
      Like myoblasts, differentiated dystrophin deficient myotubes were able to
      degenerate via apoptosis, showing that mature dystrophin deficient cells are
      fragile and undergo apoptosis when subjected to a mild injury which would
      normally be repaired in parental cells.

PMID- 9756338
TI  - Intracellular calcium and arachidonic acid increase SNAP-25 expression in
      cultured rat hippocampal explants, but not in cultured rat cerebellar explants.
AB  - The effects of the increase of intracellular calcium, induced by membrane
      depolarization with 50 mM KCl, and arachidonic acid (AA) on the expression of 25
      kD synaptosomal-associated protein (SNAP-25) were studied in cultured rat
      hippocampal and cerebellar explants, and PC12 rat pheochromocytoma cells, using
      immunoblot analysis. Incubation periods of 24 h and 48 h in 50 mM KCl increased
      SNAP-25 levels in hippocampal explants and PC12 cells, but not on cerebellar
      explants. Otherwise, a 24 h incubation with 10 microM AA increased SNAP-25
      expression only in hippocampal explants, although 100 ng/ml phorbol 12-myristate
      13-acetate (PMA) did not have effect. These results indicate that intracellular
      calcium and AA can modulate the expression of SNAP-25, depending on the origin of
      the tissue.

PMID- 9756339
TI  - Expression and coupling of somatostatin receptors in rat adrenal (PC12) and
      pituitary (GC) cell lines.
AB  - Somatostatin (somatotropin release-inhibiting factor, SRIF) interacts with G
      protein coupled receptors (sst) designated sst1 through sst5. In PC12 and GC
      cells, SRIF binding sites were identified and mRNA receptor expression was
      evaluated. SRIF binding sites were expressed at a much lower density in PC12 (Kd
      = 21.2 +/- 3.9 nM; Bmax = 31 +/- 8 fmol/mg protein) than in GC cells (Kd = 6.4 +/
      1.6 nM; Bmax = 643 +/- 29 fmol/mg protein). sst3 receptor mRNA (81% of the
      total) was mainly expressed in PC12 cells, while sst1/2 receptor mRNAs were
      mostly expressed in GC cells (64 and 29%, respectively). In PC12 cells, adenylyl
      cyclase (AC) activity was unaffected by SRIF-14 (binding all SRIF receptors),
      octreotide (specific for sst2/3/5 receptors), BIM 23056 (binding sst3/5
      receptors) or CH275 (specific for sst1 receptors), 1 microM each. In GC cells,
      SRIF-14 or octreotide, but not the two other peptides, significantly inhibited AC
      activity.

PMID- 9756340
TI  - The vagal origin of preganglionic fibers containing nitric oxide synthase in the
      guinea-pig heart.
AB  - The origin of nerve fibers projecting to the guinea pig heart that contain nitric
      oxide synthase (NOS) were studied by unilateral cervical vagotomy. Three kinds of
      NOS-immunoreactive (NOS-ir) nerve fibers are distributed in the control guinea
      pig heart: the sparse network covering the right atrium, the basket-like endings
      around intracardiac neuronal cell bodies in the small ganglia located in the left
      atrium and the interatrial septum, and the axons situated in the septal region.
      The sparse network in the right atrium did not change after vagotomy of right or
      left side. In the whole mount preparations of right atrium, we often traced
      labeled axons from the somata to join the network covering the right atrium.
      Therefore, most of this network of labeled fibers must be of intrinsic origin.
      Because the basket-like endings around neuronal cell bodies in the ganglia in the
      left atrium and the septum disappeared completely after vagotomy of left side, we
      conclude that they are parasympathetic preganglionic fibers originating from the
      left vagus nerve. NOS-ir cell bodies and the positive fibers in the
      atrioventricular nodal region survived after vagotomy. All of such nerve fibers
      were unmyelinated axons. Therefore, they seem to be the postganglionic fibers
      arising from the ganglia located in the left atrium or the septum.

PMID- 9756341
TI  - Highly variable distribution of HSV-1-specific DNA in human geniculate,
      vestibular and spiral ganglia.
AB  - Viral reactivation in temporal ganglia is the suspected cause of Bell's palsy,
      vestibular neuritis and sudden hearing loss. Since the distribution of latent
      herpes simplex type 1 (HSV-1) in geniculate, vestibular and spiral ganglia of
      individual human temporal bones could have implications for the explanation of
      isolated as well as combined disorders of these three cranial nerves, we examined
      these ganglia in 18 human temporal bones of adults by nested polymerase chain
      reaction. In all of the temporal bones HSV-1 specific DNA was detected: 10/18
      (56%) of the geniculate, 11/18 (61%) of the vestibular and 9/18 (50%) of the
      spiral ganglia samples were positive. All combinations of positive and negative
      ganglia were found in individual temporal bones at roughly equal frequencies.
      These data support a viral etiology of all three conditions, especially their
      occasional combinations.

PMID- 9756342
TI  - The proportion of isolated rat dorsal root ganglion neurones responding to
      bradykinin increases with time in culture.
AB  - The proportion of isolated rodent dorsal root ganglion neurones expressing
      bradykinin receptors increases transiently with time in culture. However, it has
      not yet been investigated whether these receptors are functioning. Therefore the
      responses of these neurones to bradykinin (1 microM) were investigated in patch
      clamp experiments in the current clamp mode after 0.8 and 1.8 days under culture
      conditions. The proportion of neurones responding to bradykinin was 26% (5/19) at
      day 0.8 and increased to 73% (16/22) at day 1.8. The intensity of the response
      was assessed by counting the number of action potentials evoked by bradykinin
      within four fixed intervals of 500 ms duration during each experiment. It
      increased with time in culture from an average of 8 +/- 2 (SD) at day 0.8 to 16
      +/- 6 at day 1.8, respectively. These results provide evidence for the induction
      of functioning bradykinin receptors in cultured dorsal root ganglion neurones
      with time in culture.

PMID- 9756343
TI  - Differential effects of treatment with nerve growth factor on thermal nociception
      and on calcitonin gene-related peptide content of primary afferent neurons in the
      rat.
AB  - We have investigated the effect of repeated systemic administration of nerve
      growth factor (NGF) to rats on (a) the calcitonin gene-related (CGRP) content of
      primary afferent neurons and (b) the thermal nociceptive threshold in normal and
      inflamed hind paws. NGF (0.1 mg/kg s.c.) was administered every other day for 7
      days. After each injection of NGF there was transient thermal hyperalgesia
      lasting less than 23 h. One day after the last of four NGF injections, there was
      no detectable difference of the thermal nociceptive threshold between the NGF
      treated and control group. NGF treatment caused, however, a significant increase
      of the concentration of immunoreactive (IR) CGRP in the sciatic nerves and paw
      skin while it had no significant effect on CGRP-IR in the stomach or ureter. A
      separate set of experiments showed that intraplantar injection of complete
      Freund's adjuvant (CFA) in NGF-treated rats caused thermal hyperalgesia and edema
      that was not significantly different from values obtained in the control group.
      The results suggest that prolonged treatment of rats with moderate doses of NGF
      is sufficient to stimulate neuropeptide synthesis in primary afferent neurons
      without causing long-lasting changes in thermal nociceptive threshold.

PMID- 9756344
TI  - Differential expression of group I metabotropic glutamate receptors (mGluRs) in
      the rat pheochromocytoma cell line PC12: role of nerve growth factor and ras.
AB  - Glutamate treatment of PC12 cells has been shown to result in the accumulation of
      intracellular inositol phosphates suggesting the presence of glutamate
      metabotropic receptors (mGluRs) positively coupled to phospholipase C. The
      present study examined the expression of group I mGluRs (mGluR1 and mGluR5) in
      PC12 cells. Undifferentiated PC12 cells were found to express both mGluR5 mRNA
      and receptor protein by reverse transcription polymerase chain reaction (RT-PCR)
      and western blot techniques. However, mGluR1 mRNA was not detected in these cells
      and western blot analysis showed only faint mGluR1alpha immunoreactivity
      suggesting a very low level of mGluR1 expression. Nerve growth factor-induced
      differentiation of PC12 cells resulted in the induction of mGluR1alpha and
      mGluR1beta mRNA and mGluR1alpha protein. PC12 cells overexpressing dominant
      negative ras revealed that NGF-induced mGluR1 induction, but not mGluR5
      expression, is dependent on ras pathway activation in these cells. These results
      suggest PC12 cells may be a useful model for investigating the regulation and
      expression of group I mGluR isoforms and their role in neuronal processes in
      vitro.

PMID- 9756345
TI  - Pulse exposure of cultured rat neurons to aluminum-maltol affected the axonal
      transport system.
AB  - Although chronic aluminum neurotoxicity has been well established, the mechanism
      of the toxicity has not been elucidated yet. In order to simplify the study of
      the aluminum neurotoxicity, we employed the pulse exposure of cultured rat
      cortical neurons to 250 microM aluminum-maltol for 1 h at the early stage (6 h
      after plating), which resulted in abnormal distribution of neurofilament L (NFL)
      and fast axonal transported proteins, whereas the axonal transport of tubulin,
      actin, and clathrin were not impaired. Otherwise, the pulse exposure of neurons
      at the late stage (4 days after plating) to the same concentration of aluminum
      maltol did not affect the cell morphology and the distribution of NFL. The pulse
      exposure of cultured neurons to aluminum-maltol at the early stage might affect
      the axonal transport system of NFL and fast axonal transported proteins.

PMID- 9756346
TI  - Heat shock protein expression protects against death following exposure to
      heatstroke in rats.
AB  - Rats 0, 16, or 48 h after heat shock (42 degrees C core temperature for 15 min)
      or chemical stress (5 mg/kg sodium arsenite, i.p.) were exposed to a high ambient
      temperature (43 degrees C) to induce heatstroke onset. The moment in which the
      mean arterial pressure and cerebral blood flow began to decrease from their peak
      values was taken as the onset of heatstroke. Prior heat shock or chemical stress
      conferred significant protection against heatstroke-induced arterial hypotension,
      cerebral ischemia, cerebral neuronal damage and death, and correlated with
      expression of HSP72 in brain, heart, liver and kidney at 16 h. However, at 48 h,
      when HSP72 expression returned to basal values, the above responses that occurred
      after the onset of heatstroke of two groups (0 h group VS 48 h group) were
      indistinguishable. The data suggest that HSP72 presence increases survival in rat
      heatstroke by attenuating arterial hypotension, cerebral ischemia and neuronal
      damage.

PMID- 9756347
TI  - Regulation of cannabinoid and mu opioid receptors in rat lumbar spinal cord
      following neonatal capsaicin treatment.
AB  - In vitro receptor binding and quantitative autoradiography were used to determine
      whether cannabinoid receptors in rat lumbar spinal cord are localized to the
      central terminals of nociceptive primary afferents. Rats were treated as neonates
      with capsaicin to destroy sensory C-fibers. The densities of cannabinoid and mu
      opioid receptors in the spinal cord of the adult rats were compared with age
      matched vehicle controls. Neonatal capsaicin produced a moderate but reliable
      suppression (16%) of [3H]CP55,940 binding to cannabinoid receptors. By contrast,
      the binding of [3H][D-Ala2-MePhe4,Gly-ol5]enkephalin (DAMGO) to mu receptors was
      depleted by approximately 60% in near adjacent sections. These data suggest that
      only a subpopulation of cannabinoid receptors is situated on the central
      terminals of primary afferent C-fibers. The present data provide anatomical
      evidence for a dissociation between cannabinoid and mu opioid modulation of
      sensory transmission at the level of the primary afferent inputs to the spinal
      cord.

PMID- 9756348
TI  - Anti-gamma interferon can prevent the premature death of trisomy 16 mouse
      cortical neurons in culture.
AB  - Previous reports have indicated that human trisomy 21 and mouse trisomy 16
      neurons exhibit decreased viability in culture when compared to euploid control
      cultures and that trisomic cells are significantly more sensitive to the anti
      cellular effects of the interferons. In the study reported here, cortical neurons
      from euploid and trisomy 16 mouse fetuses were treated with either anti-gamma
      interferon or non-specific IgG and neuron morphology and viability measured
      photographically. The addition of anti-gamma-interferon IgG to the culture media
      had no effect on euploid neurons, but significantly increased trisomy neuron
      viability throughout the 5-day culture period. Assay of both DNA fragmentation
      and phosphatidylserine externalization suggested that the trisomic neurons were
      undergoing apoptosis at a significantly higher rate than their euploid
      counterparts and that this increase in apoptosis could be almost completely
      prevented by addition of either ligand purified monoclonal or ligand purified
      polyclonal anti-gamma-interferon IgG. Taken together, these data suggest that
      endogenous interferon plays an important role in the premature death of the
      trisomy neuron.

PMID- 9756349
TI  - Melatonin inhibits the increase of cyclic AMP in rat suprachiasmatic neurons
      induced by vasoactive intestinal peptide.
AB  - The effects of melatonin on basal and vasoactive intestinal peptide (VIP)-induced
      cAMP concentration was studied in dispersed cells of the rat suprachiasmatic
      nuclei (SCN). Our data indicate, that VIP induces a rapid increase of cAMP
      concentration in the cells followed by a slow and prolonged increase in the
      medium. The VIP-induced increase was dose-dependent in the range of 1-100 nM.
      Melatonin had no effect on basal cAMP but inhibited the cAMP increase induced by
      VIP in a dose-dependent manner (EC50 = 0.21 nM). Our observations indicate that
      melatonin acts through the inhibition of cAMP in the SCN cells similar as shown
      in other tissues.

PMID- 9756350
TI  - The negative influence of endogenous opioid receptor activity on the
      differentiation of the rat pheochromocytoma PC12 cells induced by nerve growth
      factor.
AB  - We determined the effect of naloxone and morphine on the differentiation of
      pheochromocytoma cell, the PC12 cells, induced by nerve growth factor (NGF). PC12
      cells were grown in medium containing NGF with or without the addition of
      naloxone or morphine for up to 10-day treatments. NGF-induced morphological
      differentiation of PC12 cells was manifested by an increase in the percentage of
      differentiated cells and the average length of neurite per cell. Co-addition of
      morphine with NGF did not affect both parameters as compared to that of NGF
      alone. On the contrary, co-addition of naloxone with NGF significantly increased
      the percentage of differentiated cells, but did not affect the outgrowth of
      neurites. This effect of naloxone was reversed by the addition of morphine,
      suggesting that naloxone produced its effect by inhibiting the endogenous
      activity of opioid receptor. This study indicates a significant functional role
      of opioid receptor in NGF-induced differentiation of PC12 cells.

PMID- 9756351
TI  - H+-sensitivity of cultured neurons from the dorsomedial and ventrolateral medulla
      of neonate rats.
AB  - The H+-sensitivity of neonate rat cultured neurons derived from the dorsomedial
      medulla (DMM) containing the nucleus tractus solitarii and the ventrolateral
      medulla (VLM) was determined by H+-sensitive fluorescent probe BCECF-AM and
      immunohistochemical methods. Against an extracellular pH as low as 7.2-7.3, H+
      sensitivity was verified in 2.6% of the DMM neurons (46/ 1800) and 2.1% of the
      VLM neurons (38/1800). This H+-sensitive neurons of the DMM were immunoreactive
      to glutamate (52.4%) and glutamic acid decarboxylase (GAD) (28.6%), while those
      of the VLM were immunoreactive to glutamate (66.7%) and GAD (33.3%). There was no
      immunoreactivity to tyrosine hydroxylase, phenylethanolamine-N-methyltransferase
      or choline acetyltransferase in the H+-sensitive neurons are present in the DMM
      and VLM besides the ventral medullary surface, the site of the central
      chemoreceptors.

PMID- 9756352
TI  - Reduced O-glycosylated clathrin assembly protein AP180: implication for synaptic
      vesicle recycling dysfunction in Alzheimer's disease.
AB  - Synapse loss is one of the neuropathologies in Alzheimer's disease (AD) that may
      play a crucial role in the mechanism of its distinct cognitive impairment and
      dementia. In a previous study [18], a significant reduction of O-glycosylated
      clathrin assembly protein AP180 was observed in neocortex of AD. The reduction
      correlated with the density of neurofibrillary tangles. In this study we further
      determine that the O-GlcNAc/AP180 ratio is not changed, but the level of AP180
      protein decreases in AD. Furthermore, whereas the level of neurofilament (NF-M)
      remains relatively unchanged, another clathrin assembly protein, AP-2, is also
      reduced in AD along with a small loss of synaptophysin. Our findings suggest that
      synaptic vesicle recycling dysfunction may be involved in the pathology of
      synapse loss in AD.

PMID- 9756353
TI  - A parametric analysis of the 'rate effect' in the sensorimotor cortex: a
      functional magnetic resonance imaging analysis in human subjects.
AB  - We studied the effects of different movement speeds of unimanual right hand
      movements on functional magnetic resonance signal changes in the sensorimotor
      cortex using echo planar imaging (EPI). Six healthy right-handed subjects were
      scanned at rest and while executing a finger tapping task with their right index
      finger. Movement frequency was visually paced at rates ranging from 0.5 to 5 Hz,
      separated by 0.5 Hz steps. The blood oxygen level dependent (BOLD) response
      within the left sensorimotor cortex was linearly and positively related to
      movement frequency. However, this relation holds (r2 = 0.91) only for movement
      frequencies faster than 1 Hz (1.5-5 Hz). For the slower frequencies there was an
      initial sharp increase of the BOLD response from 0.5 to 1 Hz followed by an
      activity drop for 1.5 Hz. These results are compatible with the idea that two
      different motor control modes are operative during slow or fast movements. During
      slow movements a computational demanding on-line feedback control mode is
      operative resulting in strong BOLD signals indicating extensive neural activity.
      During faster movements on the other hand a program-like motor control mode is
      operative resulting in less demanding neural computations. The amount of neural
      computation for the latter control mode increases with increasing movement speed.

PMID- 9756354
TI  - The action of local anaesthetics on the compound action potential is altered by
      the nature of the permeant ion in frog nerve.
AB  - Compound action potentials were recorded from the isolated frog sciatic nerve
      using either sodium or lithium as the permeant ion, and an assessment of the
      action of local anaesthetics was made. The compound action potentials evoked from
      the nerve were not different in terms of their mean amplitude or time to peak
      whether recorded with sodium or lithium as the permeant ion. The local
      anaesthetics tested, procaine, lignocaine and benzocaine, were more potent, as
      measured by their IC50 values, by 2.3, 2.1 and 1.8 times, respectively, when
      lithium rather than sodium was used as the permeant ion. The sensitivity of the
      nerves to tetrodotoxin was not significantly different whether sodium or lithium
      was used as the permeant ion. The slope of the concentration inhibition curves
      was not significantly altered in the presence of sodium or lithium for any of the
      compounds tested. These results are consistent with the idea that the binding
      site for local anaesthetics is intimately associated with the pore region of the
      channel and that the nature of the permeant ion can alter the interaction of the
      drugs with the sodium channel. However, since this is not a common feature of all
      compounds which block sodium channels by interacting at the pore, it may help
      refine the existing structural models of sodium channels.

PMID- 9756355
TI  - Effect of sciatic nerve crush on local and target tissue production of
      neurotrophin-3 transcripts in rats.
AB  - The effect of sciatic nerve crush in adult rats on neurotrophin-3 (NT-3) mRNA
      expression at the site of crush and in ipsilateral foot skin was studied using
      competitive reverse transcription-polymerase chain reaction (cRT-PCR). Mid
      sciatic nerve crush resulted in a significant reduction in the expression of NT-3
      mRNA in nerve segments distal to the injury site at 3 and 7 days (approximate 60%
      decrease; P < 0.01). The reduced NT-3 rnRNA expression started to increase at
      days 14 post-crush and returned towards control levels at 21 days following the
      crush. The nerve segment proximal to the crush site showed a similar changed
      pattern of NT-3 mRNA expression. The effects of denervation on NT-3 mRNA
      expression in foot skin were also studied. Reduced expression of NT-3 was
      observed by 7 days post-crush, with a 25% decrease observed by 14 days (P <
      0.002). Levels of NT-3 mRNA had returned to normal by 21 days post-crush. The
      results show that changes in axon-Schwann cell contact do not account for the
      nerve crush induced loss, or subsequent recovery, of NT-3 mRNA expression in
      nerve.

PMID- 9756356
TI  - Effects of alpha-pompilidotoxin on synchronized firing in networks of rat
      cortical neurons.
AB  - We studied the effect of a novel neurotoxin, alpha-pompilidotoxin (alpha-PMTX) on
      the spontaneously synchronized network firing of cultured rat cortical neurons.
      Alpha-PMTX acted immediately and irreversibly to disrupt synchronous activity,
      leaving only residual sparse, uncorrelated firing and was effective at
      concentrations of 10 nM. In the presence of bicuculline to block inhibitory
      synaptic transmission, the shutdown in synchronized activity occurred with a
      significant delay, required a higher concentration of alpha-PMTX (> 100 nM), and
      was preceded by a transiently increased level of firing. It appears that both
      inhibitory and excitatory neuronal activity or synaptic transmission are
      amplified by alpha-PMTX, but that intense activity eventually leads to
      inactivation or transmitter depletion.

PMID- 9756357
TI  - The anti-craving drug acamprosate inhibits the conditioned place aversion induced
      by naloxone-precipitated morphine withdrawal in rats.
AB  - The anti-craving drug acamprosate (Ca N-acetylhomotaurinate) is therapeutically
      used to prevent a relapse in weaned alcoholics. In the present place conditioning
      study, the effect of this compound on the motivational impact of morphine
      withdrawal was examined. Withdrawal was precipitated in rats by administration of
      the opioid antagonist naloxone (0.1 mg/kg, s.c.) 5-6 days after the subcutaneous
      implantation of a 75 mg morphine pellet. Aversion against the naloxone-paired
      cues was observed after conditioning in the drug-free state. The acquisition of
      conditioned place aversion was completely inhibited by the pretreatment with
      acamprosate (200 mg/kg, i.p.) 12 h and 30 min prior to conditioning. These
      results clarify that acamprosate inhibits the motivational component of morphine
      withdrawal and suggest that ethanol and opiates share similar properties in the
      neuronal mechanisms of conditioned withdrawal and craving.

PMID- 9756358
TI  - Evidence for the activity of five adenosine-3',5'-monophosphate-degrading
      phosphodiesterase isozymes in the adult rat neocortex.
AB  - In the present study, the expression of the activity of adenosine-3',5'
      monophosphate-degrading phosphodiesterases (cAMP-PDEs) was analyzed in rat
      neocortex homogenates. Following separation by anion-exchange chromatography, the
      isozymes were characterized by their sensitivity to modulators and by their
      kinetic properties. We identified the activity of five distinct cAMP-PDE
      isozymes: two calcium/calmodulin-dependent forms (PDE 1), one PDE 2 isozyme
      stimulated by guanosine-3',5'-monophosphate (cGMP), one cGMP-inhibited form (PDE
      3) and a cAMP-specific, rolipram-sensitive form (PDE 4). Our study provides, for
      the first time, evidence for the existence of PDE 3 enzyme activity in rat
      neocortex and predicts the expression of at least two isoforms (splice variants)
      of PDE 1A in this brain area. The existence of different cAMP-degrading
      phosphodiesterases modulated by different intracellular second messengers
      (calcium and cGMP) suggests that the activity of neocortical neurons and glia
      cells is regulated, inter alia, by a 'crosstalk' between calcium-, cGMP- and cAMP
      dependent second messenger pathways.

PMID- 9756359
TI  - The role of N-methyl-D-aspartate receptor in the guinea pig inner ear after
      unilateral labyrinthectomy.
AB  - To investigate the role of the N-methyl-D-aspartate (NMDA) receptor in the
      vestibular periphery, vestibular compensation in the guinea pig was studied
      following chemical unilateral labyrinthectomy by osmotic pump administration of
      streptomycin sulfate (SM) with or without D-2-amino-5-phosphonovalerate (D-APV),
      one of the NMDA receptor antagonists. All animals administrated SM (SM group) or
      SM and D-APV (SM + D-APV group) showed spontaneous nystagmus and head tilt. The
      maximum degree of yaw head tilt in the SM + D-APV group was statistically smaller
      than that in the SM group. Moreover the time constant for head tilt in the SM + D
      APV group was statistically shorter than that in the SM group. These results
      indicate that the NMDA receptor in the vestibular periphery influences vestibular
      compensation after unilateral labyrinthectomy.

PMID- 9756360
TI  - Voltage- and use-dependent inhibition by amphetamine of field potentials and Na+
      current in rat nucleus accumbens neurons.
AB  - The psychostimulant amphetamine (AMPH) is known to act as an indirect dopamine
      agonist by promoting dopamine release. Here we demonstrate direct AMPH inhibition
      of field potentials and Na+ currents in rat nucleus accumbens (NAc) neurons. The
      experiments were done with field potential recordings from NAc slices and whole
      cell recordings from isolated NAc neurons. In NAc slices, AMPH inhibited the
      field potentials. The inhibition increased when the NAc neurons were depolarized
      with higher extracellular K+ or when the field potentials were evoked at a higher
      rate. In isolated NAc neurons, AMPH inhibited the Na+ currents. The inhibition
      increased when Na+ currents were activated from more depolarized holding
      potentials or were activated more frequently. The voltage- and use-dependent
      inhibition of field potentials and Na+ currents by AMPH suggests a similar
      mechanism of AMPH action with local anesthetics and antiarrhythmic drugs.

PMID- 9756361
TI  - Identification of shyc, a novel gene expressed in the murine developing and adult
      nervous system.
AB  - The embryonal carcinoma cell line P19 responds to treatment with retinoid acid by
      differentiation into neuronal cell types [2]. Using radioactively labeled cDNA
      derived from differentiating P19 cells we screened an adult mouse brain cDNA
      library and isolated a gene named shyc for selective hybridizing clone. The
      encoded protein did not reveal homology to any known protein. We used in situ
      hybridization on mouse embryonic and adult brain sections to study shyc
      expression. The developing and embryonic nervous system showed the most prominent
      hybridization signals. In the adult brain the olfactory pathway was marked by
      shyc expression.

PMID- 9756362
TI  - Serotonin2A receptor-like immunoreactivity in rat cerebellar Purkinje cells.
AB  - In the present study we examined the distribution pattern of serotonin2A (5-HT2A)
      receptors in the rat cerebellum. A strong immunoreaction against 5-HT2A receptor
      protein was observed in Purkinje cells. A dense cluster of immunopositive
      dendritic profiles of Purkinje cells was located beneath the pia matter of
      cerebellar cortex. Somal profiles in the cerebellar nuclei had weak to moderate
      immunoreactions.

PMID- 9756363
TI  - Programs promoting timely sequential antimicrobial therapy: an American
      perspective.
AB  - Interventional programs promoting the timely conversion of intravenous to oral
      antimicrobial therapy have been reported from several hospitals in the U.S.A. and
      elsewhere. Factors influencing the initiation and conduct of these programs
      include technological advances, changes in health care delivery or reimbursement,
      publication of supportive clinical data and growth of clinical pharmacy services.
      Successful programs employ comprehensive, multidisciplinary strategies to contain
      antimicrobial-related expenditures using interventions based on structured
      criteria. Future emphasis on cost-effective drug therapy, advances in computer
      based information technology and development of care maps can have favourable
      influences on the growth of these programs in the U.S.A.

PMID- 9756364
TI  - Strategies to rationalize sepsis management--a review of 4 years' experience in
      Dundee.
AB  - Hospitals worldwide are facing an unprecedented crisis of rising cost of
      antibacterials due to the increasing rapid emergence and dissemination of
      antibiotic-resistant organisms, improper use of antibiotics and the use of broad
      spectrum parenteral agents. The last 25 years has seen the introduction of many
      measures to improve the quality of sepsis management, and specifically
      antimicrobial use. The present paper reviews the development, implementation and
      evaluation of some of the key strategies employed within the Dundee Teaching
      Hospitals NHS Trust (DTHT) to enhance recognition and assessment of sepsis and to
      rationalize the early and often empiric antibiotic treatment of patients in
      hospital with infection. Particular emphasis is given to optimizing the use of
      expensive parenteral agents in conjunction with promotion of oral switch therapy
      where appropriate.

PMID- 9756365
TI  - Sequential antimicrobial therapy: comparison of the views of microbiologists and
      pharmacists.
AB  - Sequential antimicrobial therapy (SAT) is arousing keen interest in
      microbiologists and pharmacists. In an attempt to obtain information from these
      groups regarding the use of SAT in hospitals, an anonymized postal survey was
      carried out. A SAT questionnaire was circulated to consultant medical
      microbiologists, clinical microbiologists, and heads of pharmacy departments
      within the British Isles. Four hundred and forty-seven microbiologists and
      pharmacists returned completed questionnaires, giving a response rate of 29%.
      Just over half of medical microbiologists (MM) and pharmacists (PH) indicated
      that SAT was used in their institution in respiratory medicine, geriatrics,
      surgery and, significantly, to a lesser degree in paediatrics. The most common
      infections treated were pneumonia, bronchitis and wound infection. However, there
      were significant differences between MM and PH, with MM favouring greater use of
      SAT in peritonitis (P=0.03), septicaemia (P<0.01), bone infection (P<0.01),
      pyelonephritis (UTI) (P<0.01), and PH favouring use in bronchitis (P<0.01). The
      ability to take oral fluids or a recognition of no potential absorption problems
      were key criteria in the decision process leading to the institution of SAT by MM
      and PH. Significantly more MM favoured employing criteria such as temperature <38
      degrees C (P<0.01), no requirement for high tissue concentrations (P=0.02) and
      evidence of response to i.v. antimicrobial therapy (P<0.01) than PH. The most
      frequently "switched" antimicrobials were metronidazole, ciprofloxacin and co
      amoxiclav. There were more than five times as many MM reporting the use of
      clindamycin than PH (P<0.01), whereas nearly twice as many PH cited use of
      cefuroxime (P<0.01). Of those hospitals not employing SAT, most MM and PH
      concurred that the commonest reason to institute SAT was financial, followed by
      convenience to patients and staff. However, more PH than MM indicated that
      protocols (P<0.01) and a reduction in i.v. complications (P<0.01) were important
      to them. In promoting SAT, MM and PH felt they had the major role. Significantly,
      each profession felt that the other had a lesser role to play; MM as judged by
      the PH (P<0.01) and PH as judged by MM (P<0.01). When promoting SAT, both MM and
      PH felt that "education for clinicians" followed by regular audit was the best
      way to ensure implementation. However, significant differences arose with PH
      regarding nurse education (P<0.01), SAT posters (P=0.02), regular review of
      patients (P=0.04) and patient's notes SAT stickers (P<0.01) as more important to
      them than MM. Significantly, less MM than PH (P<0.01) insisted that either the
      i.v. and PO antimicrobials were identical or were from the same group or class
      when "switching". This survey highlights interesting comparisons between the
      approaches of MM and PH towards SAT and may indicate ways in which both groups
      may work together to bring about change.

PMID- 9756366
TI  - Assessment criteria in identifying the sick sepsis patient.
AB  - Standard definitions of sepsis have been proposed and have been widely adopted.
      Recognition of the systemic inflammatory response syndrome (SIRS) and assessment
      of its severity can easily be achieved at the bedside using basic observations
      and simple laboratory tests. Fulfillment of standardized criteria defining
      increasing severity of sepsis or manifestation of two, three and four SIRS
      criteria directly correlates with risk of mortality and progression to organ
      failure. However, manifestation of only two SIRS criteria identifies patients who
      may have relatively mild disease. Furthermore, sepsis definitions take no account
      of pre-existing illness, source of infection or causative agent, all of which
      have a significant influence on outcome. Despite these limitations, manifestation
      of four SIRS criteria or the persistence of markers of severe sepsis identifies
      individuals on general wards who are at particularly high risk of death, who
      should be closely monitored for deterioration and discussed with an intensive
      care physician at an early stage. If the source of sepsis is not clear, empirical
      antibiotic therapy for such individuals should be discussed with a medical
      microbiologist or infectious diseases physician.

PMID- 9756367
TI  - Sequential antimicrobial therapy: pharmacokinetic and pharmacodynamic
      considerations in sequential therapy.
AB  - The pharmacodynamic factors important in sequential therapy are largely unknown.
      This is because most pharmacodynamic investigations concentrate on how bacterial
      populations respond to first antimicrobial exposures. However, it is likely that
      for B lactams T>MIC and for quinolones the antimicrobial AUC/MIC ratio will be
      important. Factors which reduce antimicrobial absorption will impact on these
      parameters and require further study.

PMID- 9756368
TI  - Sequential antibiotic therapy: the right patient, the right time and the right
      outcome.
AB  - The aim of sequential therapy should be to provide better quality of care at
      lower cost. In comparison with i.v. therapy, oral administration is safer, more
      acceptable to the patient, facilitates early discharge from hospital and reduces
      the cost of consumables. However, if given to the wrong patient, oral
      antimicrobial therapy could both increase the cost and reduce the quality of
      care, either because of ineffective treatment, or unnecessary prolongation of
      treatment. Hospitals must develop policies for sequential therapy which define
      standards against which clinical care can be audited. The standards will need to
      be revised as new data become available from local audit and from research.
      Further research on sequential therapy is undoubtedly required, with particular
      emphasis on the reliability of absorption of oral drugs by hospitalized patients.

PMID- 9756369
TI  - Cost issues in sequential therapy.
AB  - Pharmacoeconomics is starting to be employed in strategic therapeutic decision
      making. Costs associated with antimicrobials included: (i) acquisition costs;
      (ii) preparation, administration and consumables costs; (iii) monitoring costs;
      (iv) costs of unwanted drug effects; (v) costs of resistance and therapeutic
      failures and (vi) costs of duration of stay. Most hospitals have a Drug and
      Therapeutics Committee but acquisition costs are still the most important
      economic criterion for acceptance for use, even though medicines only consume
      between 3 and 5% of total revenue costs, of which antibiotics account for around
      15%. In any sequential programme acquisition costs and consumables are
      immediately realizable. Staff time and monitoring tests are less realizable but
      require changes in the way budgets are handled. Microbial resistance and risk
      management are difficult to quantify but are increasingly becoming important in
      strategic decision-making. The educational needs of health care decision makers
      in economic need addressing and mechanisms need to be put in place to enable the
      putative savings reported in the pharmacoeconomic literature to be realized.

PMID- 9756370
TI  - Implementation of sequential therapy programs--a microbiologist's view.
AB  - Sequential antimicrobial therapy is not new, but confusion about the timing and
      nature of the switch often negates perceived advantages. A common problem is the
      choice of oral antibiotic to follow empirical administration of an intravenous
      second or third generation cephalosporin. Where guidelines do not exist,
      particularly when data are lacking as the the best option, the Delphi technique
      of obtaining a consensus agreement by review of a series of case histories is
      recommended. Majority verdicts are used to determine what is acceptable practice,
      and as such the approach is also suitable for audit. Savings through reduced drug
      acquisition costs and shorter lengths of stay have been highlighted. However,
      other less obvious potential benefits of sequential antimicrobial therapy include
      reduced incidence of intravascular catheter infection because of shorter line
      dwell times and less endoluminal contamination. Sequential antimicrobial therapy
      may also be used as part of a policy to reduce the selective pressure,
      particularly due to cephalosporin use, for endemic hospital pathogens such as
      Clostridium difficile and extended spectrum producing gram-negative baccilli.

PMID- 9756371
TI  - Implementation of sequential therapy programmes--a pharmacist's view.
AB  - Sequential antibiotic therapy has a number of advantages in terms of patient
      benefit and value for money in drug use. Introduction and maintenance of a
      process to ensure sequential therapy is multidisciplinary, involving clinicians,
      pharmacists, microbiologists and possibly nurses. The contribution of pharmacists
      is multi-faceted and involves senior and junior pharmacists working in a number
      of areas. Pharmacy managers will be involved at policy setting level through the
      Drug and Therapeutics committee and similar bodies. Purchasing and formulary
      pharmacists will be involved in negotiating purchasing agreements while clinical
      pharmacists provide data on the costs and outcomes of treatment. The drug
      information pharmacist is a valuable resource in searching and interpreting the
      available literature. Whatever system is used, clinical pharmacists have an
      important role in identifying patients and monitoring prescribing. In many
      schemes described in the literature, pharmacists have had an important role in
      auditing the effectiveness of sequential therapy. There may be scope for
      developing the clinical pharmacist's role further by devolving, under protocol,
      increased decision making and medicines management responsibilities.

PMID- 9756372
TI  - Tumour necrosis factor-alpha as a target of melanocortins in haemorrhagic shock,
      in the anaesthetized rat.
AB  - The cytokine tumour necrosis factor-alpha (TNF-alpha) is involved (mostly through
      the activation of inducible nitric oxide synthase) in the pathogenesis of
      circulatory shock. On the other hand, melanocortin peptides are potent and
      effective in reversing haemorrhagic shock, both in animals (rat, dog) and in
      humans. This prompted us to study the influence of the melanocortin peptide ACTH
      (1-24) on the blood levels of TNF-alpha in haemorrhage-shocked rats and on the in
      vitro production of TNF-alpha by lipopolysaccharide (LPS)-activated macrophages.
      Plasma levels of TNF-alpha were undetectable before starting bleeding and greatly
      increased 20 min after bleeding termination in saline-treated rats. In rats
      treated with ACTH-(1-24) the almost complete restoration of cardiovascular
      function was associated with markedly reduced levels of TNF-alpha 20 min after
      bleeding termination. On the other hand, ACTH-(1-24) did not influence TNF-alpha
      plasma levels in sham-operated, unbled rats. In vitro, ACTH-(1-24) (25-100 nM)
      dose-dependently reduced the LPS-stimulated production of TNF-alpha by peritoneal
      macrophages harvested from untreated, unbled rats. These results indicate that
      inhibition of TNF-alpha overproduction may be an important component of the
      mechanism of action of melanocortins in reversing haemorrhagic shock.

PMID- 9756373
TI  - Potent antihyperglycaemic property of a new imidazoline derivative S-22068 (PMS
      847) in a rat model of NIDDM.
AB  - Recent data suggest that some imidazoline derivatives can lower plasma glucose in
      experimental animal models of diabetes. We studied the activity of an imidazoline
      S-22068, in rat model of non-insulin-dependent diabetes mellitus (NIDDM) produced
      with a low dose of streptozotocin (35 mg kg(-1), i.v.) in the adult. The
      respective increase over basal value in glucose (deltaG) and insulin (deltaI),
      and the rate of glucose disappearance (K), were measured during a 30 min
      intravenous glucose tolerance test. After an intraperitoneal injection of S-22068
      (24 mg kg(-1)), deltaG (mM min(-1)) was decreased (91.67+/-5.83 vs 120.5+/-3.65;
      P<0.001), whereas K was increased (1.74+/-0.09 vs 1.18+/-0.05; P<0.001). Although
      insulinaemia was increased at time-point 0 of the test, deltaI was unchanged.
      During oral glucose tolerance tests (OGTT), S-22068 (24 mg kg(-1), p.o.) improved
      glucose tolerance, and its efficiency was potentiated after chronic treatment (15
      days). Basal glycaemia was unaffected by the treatment. Under the same
      conditions, a higher dose of S-22068 (40 mg kg(-1)) further improved glucose
      tolerance without causing hypoglycaemia. Binding experiments revealed that S
      22068 displays no affinity for either adrenoceptors or the two imidazoline
      receptors I1 or I2. These results demonstrate that S-22068 improves glucose
      tolerance without causing hypoglycaemia. Thus S-22068 represents a new potential
      option in the treatment of NIDDM.

PMID- 9756374
TI  - Purinoceptor activation of chloride transport in cystic fibrosis and CFTR
      transfected pancreatic cell lines.
AB  - The regulation of chloride efflux from cystic fibrosis pancreatic adenocarcinoma
      cells (CFPAC-1) and wild-type CFTR-transfected CFPAC-1 cells (TPAC) was compared.
      Forskolin (10 microM) stimulated chloride efflux from the corrected TPAC cells
      but not from CFPAC-1 cells. Chloride efflux from both cell types was activated by
      thapsigargin (0.5 microM). The nucleotides ATP and UTP and the non-hydrolyzable
      ATP analogue, adenosine 5'-O-(3-thio) triphosphate (ATPgammaS), stimulated
      chloride efflux from both cell types. None of the other P2 purinoceptor agonists
      investigated elicited a response. The order of potency was ATP > or = UTP > or =
      ATPgammaS. Adenosine (10-100 microM) activated choride efflux from the TPAC but
      not the CFPAC cell line with no increase in intracellular cyclic AMP. Small but
      statistically significant inhibitions of the adenosine-(50 microM)-stimulated
      increase in chloride efflux were elicited by the A1 receptor antagonist 8
      cyclopentyl-1,3-dipropylxanthine (CPX, 100 nM) and the A2 receptor antagonist 3,7
      dimethyl-1-propylargylxanthine (DMPX, 10 microM). The A2A receptor antagonist 8
      (3-chlorostyryl)caffeine (CSC, 100 nM) had no significant effect. These results
      provide evidence for the regulation of chloride efflux by P2Y2 purinoceptors in
      genetically-corrected and CF pancreatic cell lines. Studies with adenosine
      receptor antagonists indicate some possible involvement of A1 and A2 (but not
      A2A) receptors in the adenosine stimulation of chloride efflux, but the
      relatively small effects of the inhibitors coupled with lack of increase in
      cyclic AMP and a response only in the CFTR-transfected cells also suggests a
      possible direct effect of adenosine on CFTR.

PMID- 9756375
TI  - Presynaptic and postsynaptic actions of halothane at glutamatergic synapses in
      the mouse hippocampus.
AB  - Whole-cell patch-clamp recordings in adult mouse hippocampal slices were used to
      test the mechanism by which the volatile anesthetic halothane inhibits glutamate
      receptor-mediated synaptic transmission. Non-N-methyl-D-aspartate (nonNMDA) and
      NMDA receptor-mediated currents in CA1 pyramidal cells were pharmacologically
      isolated by bath application of D,L-2-amino-5-phosphonovaleric acid (APV; 100
      microM) or 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX; 5 microM), respectively.
      Halothane blocked both nonNMDA and NMDA receptor-mediated excitatory postsynaptic
      currents (EPSCs) to a similar extent (IC50 values of 0.66 and 0.57 mM,
      respectively). Partial blockade of the EPSCs by lowering the extracellular
      concentration of calcium ([Ca2+]o), but not by application of CNQX (1 microM),
      was accompanied by an increase in paired-pulse facilitation (PPF). Halothane
      induced blockade of the EPSCs also was associated with an increase in PPF. The
      effects of halothane on alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid
      (AMPA) and NMDA receptor-mediated currents induced by agonist iontophoresis, were
      compared. AMPA-induced currents were blocked with an IC50 of 1.7 mM. NMDA-induced
      currents were significantly less sensitive to halothane (IC50 of 5.9 mM). The
      effect of halothane on iontophoretic AMPA dose-response curves was tested.
      Halothane suppressed the maximal response to AMPA without affecting its EC50,
      suggesting a noncompetitive mechanism of inhibition. All effects of halothane
      were reversible upon termination of the exposure to the drug. These data suggest
      that halothane blocks central glutamatergic synaptic transmission by
      presynaptically inhibiting glutamate release and postsynaptically blocking the
      AMPA subtype of glutamate receptors.

PMID- 9756376
TI  - Characterization of an atypical muscarinic cholinoceptor mediating contraction of
      the guinea-pig isolated uterus.
AB  - In many smooth muscle tissues a minor M3-muscarinic acetylcholine (mACh) receptor
      population mediates contraction, despite the presence of a larger M2-mACh
      receptor population. However, this is not the case for guinea-pig uterus where
      radioligand binding and functional studies exclude a dominant role for M3-mACh
      receptors. Using tissue from animals pre-treated with diethylstilboestrol,
      estimates of antagonist affinity were made before and after selective alkylation
      procedures, together with estimates of agonist affinity to characterise the mACh
      receptor population mediating carbachol-induced contraction of guinea-pig
      isolated uterus. Antagonist affinity estimates made at 'protected' receptors were
      not significantly different from those made in untreated tissues. However all
      estimations were significantly different from those reported in guinea-pig ileum
      and atria. The rank order of affinities were atropine>zamifenacin=tripitramine>
      methoctramine. Carbachol-induced contractions were insensitive to the M4
      selective muscarinic toxin MTx-3, or PD102807 (0.1 microM) ruling out a role for
      M4-mACh receptors. The agonist affinity value for L-660,863, a putative 'M2
      selective' agonist of 5.44+/-0.30 (n=6) was significantly different from that
      reported in guinea-pig atria. In contrast, the pKA value for carbachol (4.22+/
      0.17 n = 8) agrees with that reported for guinea-pig ileum. Carbachol-induced
      contractions were insensitive to pertussis toxin although carbachol-induced
      inhibition of forskolin-stimulated cyclic AMP production was attenuated, ruling
      out the involvement of Gi-proteins in contraction. Radioligand binding studies
      revealed a KD for N-[3H]-methylscopolamine of 0.12+/-0.05 nM and a Bmax of 147+/
      18 fmol mg protein(-1). Antagonist affinity estimates made using competition
      binding studies supported previous data suggesting the presence of a homogenous
      population of M2-mACh receptors. These data suggest a small population of mACh
      receptors with an atypical operational profile which can not be distinguished
      using radioligand binding studies may mediate carbachol-induced contraction of
      guinea-pig isolated uterus.

PMID- 9756377
TI  - Mechanisms of galanin-induced contraction in the rat myometrium.
AB  - A neuropeptide, galanin, regulates the reproductive process and directly induces
      myometrial contraction. The aim of this study was to determine the mechanism of
      galanin-induced myometrial contraction. For this purpose, we simultaneously
      measured intracellular Ca2+ concentration ([Ca2+]i) and tension using fura-PE3
      fluorometry and the rat longitudinal myometrium. The effect of galanin on the
      Ca2+ sensitivity of the contractile apparatus was examined in beta-escin
      permeabilized strips. The expression of galanin and the galanin receptors mRNAs
      in the rat myometrium were determined by reverse transcription polymerase chain
      reaction (RT-PCR). Galanin (10-300 nM) induced phasic contraction with or without
      oscillation in the pregnant rat myometrium in a concentration-dependent manner.
      The maximal response was obtained at 100 nM. There was no significant difference
      either in the maximal responses or EC50 values for galanin-induced myometrial
      contractions among myometriums from non-pregnant and pregnant (day 4, day 11, day
      20, day 22) rats. In the day 20 and 22 pregnant myometriums, assigning the levels
      of [Ca2+]i and tension at 40 mM K+-depolarization to be 100%, galanin increased
      the [Ca2+]i and tension to 126.9+/-2.9% and 116.3+/-2.7%, respectively. Diltiazem
      (10 microM) inhibited the galanin-induced elevation of [Ca2+]i and tension to
      71.9+/-2.4% and 16.2+/-0.7%, respectively. Ni2+, by itself, decreased the basal
      [Ca2+]i to -50.2+/-3.9% without affecting resting tension. After Ni2+ treatment,
      galanin-induced increases in [Ca2+]i and tension were -19.6+/-3.4% and 0.9+/
      0.1%, respectively. In myometrium treated with diltiazem, no oscillation in
      [Ca2+]i and tension was observed. In Ca2+-free solution with 0.1 mM EGTA, galanin
      increased [Ca2+]i from -40.2+/-2.7% to -18.0+/-2.6% and induced transient
      contraction (3.6+/-0.8%). In beta-escin permeabilized myometrium, galanin
      enhanced the contraction induced by 0.3 microM Ca2+ in the presence of GTP. In
      the presence of GDPbetaS (1 mM) instead of GTP, galanin failed to increase the
      Ca2+ sensitivity of the contractile apparatus. RT-PCR revealed that galanin mRNA
      was hardly expressed in the non-pregnant rat myometrium and increased to reach a
      maximal level at mid pregnancy (day 11), but decreased to the same level as in
      the non-pregnant myometrium at term (day 22). Type 2 galanin receptor (GALR2)
      mRNA was found to be expressed in the rat myometrium whereas type 1 galanin
      receptor (GALR1) mRNA expression was not detected. In conclusion, galanin induces
      contraction of the rat myometrium by increasing [Ca2+]i as well as by increasing
      Ca2+ sensitivity of the contractile apparatus. Galanin-induced increases in
      [Ca2+]i are caused by both intracellular Ca2+ release and Ca2+ influx from
      extracellular space. The responsiveness of the rat myometrium to galanin does not
      change during pregnancy. The galanin mRNA is expressed in the rat myometrium and
      it is upregulated during mid-pregnancy. Rat myometrium expresses GALR2 but not
      GALR1 mRNA. By changing mRNA expression in the myometrium during pregnancy,
      galanin may act as a paracrine or autocrine mediator in the regulation of
      myometrial contractility.

PMID- 9756378
TI  - Analgesic and sedative concentrations of lignocaine shunt tonic and burst firing
      in thalamocortical neurones.
AB  - The effects of lignocaine [lidocaine] HCl (0.6 microM(-1) mM) on the membrane
      electrical properties and action potential firing of neurones of the ventral
      posterolateral (VPL) nucleus of the thalamus were investigated using whole cell
      recording techniques in rat brain slices in vitro. Bath application of lignocaine
      reversibly decreased the input resistance (Ri) of VPL neurones. This effect was
      observed at low, clinically sedative and analgesic concentrations (i.e., maximal
      amplitude at 10 microM) whereas higher concentrations (300 microM(-1) mM) had no
      effect on Ri. Lignocaine (10-100 microM) depolarized VPL neurones up to 14 mV in
      a reversible manner. Consistent with a decreased Ri, low concentrations of
      lignocaine shunted the current required for spike generation in the tonic
      pattern. Lignocaine increased the threshold amplitude of current required for
      firing and decreased the tonic firing frequency, without concomitant elevation of
      the voltage threshold for firing or reduction in the maximal rate of rise
      (dV/dt(max)) of spikes. Low concentrations of lignocaine shunted low threshold
      spike (LTS) burst firing evoked either from hyperpolarized potentials or as
      rebound bursts on depolarization from prepulse-conditioned potentials. Higher
      concentrations of lignocaine (300 microM - 1 mM), not associated with a decrease
      in Ri, elevated the voltage threshold for firing and reduced the dV/dt(max) of
      spikes in a concentration-dependent fashion. In conclusion, low concentrations of
      lignocaine shunted tonic and burst firing in VPL neurones by decreasing Ri, a
      mechanism not previously described for local anaesthetics in the CNS. We suggest
      that a decreased resistance in thalamocortical neurones contributes to the
      sedative, analgesic, and anaesthetic properties of systemic lignocaine in vivo.

PMID- 9756379
TI  - Potent inhibition of both the acute and delayed emetic responses to cisplatin in
      piglets treated with GR205171, a novel highly selective tachykinin NK1 receptor
      antagonist.
AB  - The effects of GR205171, a selective tachykinin NK1 receptor antagonist, were
      investigated on both the acute and delayed phases of cisplatin-induced nausea
      like behaviour and vomiting in the conscious piglet. Animals receiving cisplatin
      (5.5 mg kg(-1), i.v.) were observed for 60 h. Fifteen min prior to cisplatin
      infusion (T0(-15 min)), eight piglets acting as controls received an intravenous
      injection of saline solution (1 ml kg(-1)), whereas experimental animals received
      a single i.v. administration of GR205171 (1 ml kg(-1)) at a dose of 0.01 (n=8),
      0.03 (n=8), 0.1 (n = 8), 0.3 (n = 16) or 1.0 (n = 13) mg kg(-1). In eight
      additional piglets, GR205171 (1 mg kg(-1)) was administered 15 min before the
      onset of the delayed phase (T16(-15 min)). A further five piglets received
      GR205171 (1 mg kg(-1)) every 6 h throughout the experiment. The latencies of the
      first emetic episode (EE) and nausea-like behavioural episode (NE) increased in
      all experimental groups treated at T0(-15 min), and the total number of both EE
      and NE during the 60 h was reduced in a dose-dependent manner. In piglets treated
      at T0(-15 min) with GR205171 1 mg kg(-1), eight out of 13 (62%) did not vomit
      throughout the experiment. Animals treated with GR205171 (1 mg kg(-1)) at T16(-15
      min) exhibited an acute response to cisplatin but did not vomit during the
      delayed phase. The greatest inhibition of both nausea-like behaviour and vomiting
      was observed in piglets receiving multiple injections of GR205171. These results
      demonstrate the long-lasting anti-emetic effects of GR205171, and confirm the key
      role of substance P within the emetic reflex.

PMID- 9756380
TI  - Direct dopamine D2-receptor-mediated modulation of arachidonic acid release in
      transfected CHO cells without the concomitant administration of a Ca2+-mobilizing
      agent.
AB  - In CHO cells transfected with the rat dopamine D2 receptor (long isoform),
      administration of dopamine per se elicited a concentration-dependent increase in
      arachidonic acid (AA) release. The maximal effect was 197% of controls (EC50=25
      nM). The partial D2 receptor agonist, (-)-(3-hydroxyphenyl)-N-n-propylpiperidine
      [(-)-3-PPP], also induced AA release, but with somewhat lower efficacy (maximal
      effect: 165%; EC50=91 nM). The AA-releasing effect of dopamine was counteracted
      by pertussis toxin, by the inhibitor of intracellular Ca2+ release, 8-(N N
      diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8), by excluding calcium from
      the medium, by the phospholipase A2 (PLA2) inhibitor, quinacrine, and by long
      term pretreatment with the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate
      (TPA). In addition, it was antagonized by the D2 antagonists, raclopride and (-)
      sulpiride--but not by (+)-sulpiride--and absent in sham-transfected CHO cells
      devoid of D2 receptors. The results obtained contrast to the previous notion that
      dopamine and other D2 receptor agonists require the concomitant administration of
      calcium-mobilizing agents such as ATP, ionophore A-23187 (calcimycin), thrombin,
      and TRH, to influence AA release from various cell lines.

PMID- 9756381
TI  - Structural determinants for binding to CGRP receptors expressed by human SK-N-MC
      and Col 29 cells: studies with chimeric and other peptides.
AB  - Structure-activity relationships for the binding of human alpha-calcitonin gene
      related peptide 8-37 (halphaCGRP8-37) have been investigated at the CGRP
      receptors expressed by human SK-N-MC (neuroblastoma) and Col 29 (colonic
      epithelia) cells by radioligand binding assays and functional assays (halphaCGRP
      stimulation of adenylate cyclase). On SK-N-MC cells the potency order was
      halphaCGRP8-37 > halphaCGRP19-37 = AC187 > rat amylin8-37 > halpha[Tyr0]-CGRP28
      37 (apparent pKBs of 7.49+/-0.25, 5.89+/-0.20, 6.18+/-0.19, 5.85+/-0.19 and
      5.25+/-0.07). The SK-N-MC receptor appeared CGRP1-like. On Col 29 cells, only
      halphaCGRP8-37 of the above compounds was able to antagonize the actions of
      halphaCGRP (apparent pKB=6.48+/-0.28). Its receptor appeared CGRP2-like.
      halpha[Ala11,18]-CGRP8-37, where the amphipathic nature of the N-terminal alpha
      helix has been reduced, bound to SK-N-MC cells a 100 fold less strongly than
      halphaCGRP8-37. On SK-N-MC cells, halphaCGRP8-18,28-37 (M433) and mastoparan
      halphaCGRP28-37 (M432) had apparent pKBs of 6.64+/-0.16 and 6.42+/-0.26,
      suggesting that residues 19-27 play a minor role in binding. The physico-chemical
      properties of residues 8-18 may be more important than any specific side-chain
      interactions. M433 was almost as potent as halphaCGRP8-37 on Col 29 cells
      (apparent pKB=6.17+/-0.20). Other antagonists were inactive.

PMID- 9756382
TI  - Pharmacological characterization of a rat 5-hydroxytryptamine type3 receptor
      subunit (r5-HT3A(b)) expressed in Xenopus laevis oocytes.
AB  - The present study has utilized the two electrode voltage-clamp technique to
      examine the pharmacological profile of a splice variant of the rat orthologue of
      the 5-hydroxytryptamine type 3A subunit (5-HT3A(b)) heterologously expressed in
      Xenopus laevis oocytes. At negative holding potentials, bath applied 5-HT (300 nM
      - 10 microM) evoked a transient, concentration-dependent (EC50 = 1.1+/-0.1
      microM), inward current. The response reversed in sign at a holding potential of 
      2.1+/-1.6 mV. The response to 5-HT was mimicked by the 5-HT3 receptor selective
      agonists 2-methyl-5-HT (EC50= 4.1+/-0.2 microM), 1-phenylbiguanide (EC50=3.0+/
      0.1 microM), 3-chlorophenylbiguanide (EC50 = 140+/-10 nM), 3,5
      dichlorophenylbiguanide (EC50 = 14.5+/-0.4 nM) and 2,5-dichlorophenylbiguanide
      (EC50 = 10.2+/-0.6 nM). With the exception of 2-methyl-5-HT, all of the agonists
      tested elicited maximal current responses comparable to those produced by a
      saturating concentration (10 microM) of 5-HT. Responses evoked by 5-HT at EC50
      were blocked by the 5-HT3 receptor selective antagonist ondansetron (IC50=231+/
      22 pM) and by the less selective agents (+)-tubocurarine (IC50=31.9+/-0.01 nM)
      and cocaine (IC50 = 2.1+/-0.2 microM). The data are discussed in the context of
      results previously obtained with the human and mouse orthologues of the 5-HT3A
      subunit. Overall, the study reinforces the conclusion that species differences
      detected for native 5-HT3 receptors extend to, and appear largely explained by,
      differences in the properties of homo-oligomeric receptors formed from 5-HT3A
      subunit orthologues.

PMID- 9756383
TI  - U937 cells deprived of endogenous annexin 1 demonstrate an increased PLA2
      activity.
AB  - Annexin 1 (An 1), a phospholipid and calcium binding protein, is strongly
      expressed in differentiated U 937 cells. In attempting to correlate the
      expression of An 1 with phospholipase A2 (PLA2) activity, U 937 cells were stably
      transfected both with a Sense and Antisense cDNA for An 1. PLA2 activity was
      measured by Flow cytometry analysis utilizing the bis-Bodipy-C11-PC fluorescent
      probe. U 937 cells stably transfected with the sense or antisense vectors were
      differentiated for 24 h with phorbol 12-myristate 13-acetate (PMA, 6 ng ml(-1)).
      Both in undifferentiated and differentiated cells, the Antisense clone (36.4 AS)
      showed consistently higher PLA2 activity than the control Sense clone (15 S).
      Since the fluorescent probe measures the total PLA2 activity, we used two
      different stimuli, PMA: (100 ng ml(-1)) or lipopolysaccharide (LPS, 10 ng ml(
      1)), and two different inhibitors, to discriminate the PLA2 involved (namely
      arachidonyl trifluoromethyl ketone or AACOCF3, which is specific for the
      cytosolic PLA2, and SB 203347 specific for the secretory PLA2). In the Antisense
      clone the inhibitory effect of AACOCF was stronger [68%, P<0.025] than in the
      Sense, which may reflect the lower endogenous level of An 1 present in the cells.
      On the contrary, the inhibitory effect of SB 203347 [60% of inhibition] was
      identical in both clones. Since cPLA2 activity is correlated with its
      phosphorylation, Western and shift blot analysis were performed. They did not
      show any significative difference between the phosphorylated and non
      phosphorylated form of the enzyme in both the differentiated or not, Sense and
      Antisense clones. Furthermore the tyrosine phosphorylation analysis of An 1
      showed that less than 10% of An 1 was phosphorylated irrespective of PMA presence
      or absence. From the pattern of inhibition observed, we propose that the
      endogenous unphosphorylated form of An 1 may act intracellularly to block the
      activity of a cytosolic PLA2.

PMID- 9756384
TI  - Metabolic response to various beta-adrenoceptor agonists in beta3-adrenoceptor
      knockout mice: evidence for a new beta-adrenergic receptor in brown adipose
      tissue.
AB  - The beta3-adrenoceptor plays an important role in the adrenergic response of
      brown and white adipose tissues (BAT and WAT). In this study, in vitro metabolic
      responses to beta-adrenoceptor stimulation were compared in adipose tissues of
      beta3-adrenoceptor knockout and wild type mice. The measured parameters were BAT
      fragment oxygen uptake (MO2) and isolated white adipocyte lipolysis. In BAT of
      wild type mice (-)-norepinephrine maximally stimulated MO2 4.1+/-0.8 fold.
      Similar maximal stimulations were obtained with beta1-, beta2- or beta3
      adrenoceptor selective agonists (dobutamine 5.1+/-0.3, terbutaline 5.3+/-0.3 and
      CL 316,243 4.8+/-0.9 fold, respectively); in BAT of beta3-adrenoceptor knockout
      mice, the beta1- and beta2-responses were fully conserved. In BAT of wild type
      mice, the beta1/beta2-antagonist and beta3-partial agonist CGP 12177 elicited a
      maximal MO2 response (4.7+/-0.4 fold). In beta3-adrenoceptor knockout BAT, this
      response was fully conserved despite an absence of response to CL 316,243. This
      unexpected result suggests that an atypical beta-adrenoceptor, distinct from the
      beta1-, beta2- and beta3-subtypes and referred to as a putative beta4
      adrenoceptor is present in BAT and that it can mediate in vitro a maximal MO2
      stimulation. In isolated white adipocytes of wild type mice, (-)-epinephrine
      maximally stimulated lipolysis 12.1+/-2.6 fold. Similar maximal stimulations were
      obtained with beta1-, beta2- or beta3-adrenoceptor selective agonists (TO509 12+/
      2, procaterol 11+/-3, CL 316,243 11+/-3 fold, respectively) or with CGP 12177
      (7.1+/-1.5 fold). In isolated white adipocytes of beta3-adrenoceptor knockout
      mice, the lipolytic responses to (-)epinephrine, to the beta1-, beta2-, beta3
      adrenoceptor selective agonists and to CGP 12177 were almost or totally
      depressed, whereas those to ACTH, forskolin and dibutyryl cyclic AMP were
      conserved.

PMID- 9756385
TI  - Effect of increased cardiac output on liver blood flow, oxygen exchange and
      metabolic rate during longterm endotoxin-induced shock in pigs.
AB  - We investigated hepatic blood flow, O2 exchange and metabolism in porcine
      endotoxic shock (Control, n = 8; Endotoxin, n = 10) with administration of
      hydroxyethylstarch to maintain arterial pressure (MAP)>60 mmHg. Before and 12, 18
      and 24 h after starting continuous i.v. endotoxin we measured portal venous and
      hepatic arterial blood flow, intracapillary haemoglobin O2 saturation (Hb-O2%) of
      the liver surface and arterial, portal and hepatic venous lactate, pyruvate,
      glycerol and alanine concentrations. Glucose production rate was derived from the
      plasma isotope enrichment during infusion of [6,6-2H2]-glucose. Despite a
      sustained 50% increase in cardiac output endotoxin caused a progressive,
      significant fall in MAP. Liver blood flow significantly increased, but endotoxin
      affected neither hepatic O2 delivery and uptake nor mean intracapillary Hb-O2%
      and Hb-O2% frequency distributions. Endotoxin nearly doubled endogenous glucose
      production rate while hepatic lactate, alanine and glycerol uptake rates
      progressively decreased significantly. The lactate uptake rate even became
      negative (P<0.05 vs Control). Endotoxin caused portal and hepatic venous pH to
      fall significantly concomitant with significantly increased arterial, portal and
      hepatic venous lactate/pyruvate ratios. During endotoxic shock increased cardiac
      output achieved by colloid infusion maintained elevated liver blood flow and
      thereby macro- and microcirculatory O2 supply. Glucose production rate nearly
      doubled with complete dissociation of hepatic uptake of glucogenic precursors and
      glucose release. Despite well-preserved capillary oxygenation increased
      lactate/pyruvate ratios reflecting impaired cytosolic redox state suggested
      deranged liver energy balance, possibly due to the O2 requirements of
      gluconeogenesis.

PMID- 9756386
TI  - A discriminant block among K+ channel types by phenytoin in neuroblastoma cells.
AB  - The action of the anticonvulsant drug phenytoin on K+ channels was investigated
      in neuroblastoma cells (N2A) by using the single-channel patch-clamp technique.
      N2A cells expressed three types of delayed rectifier K+ channels, which were
      found to have a conductance of 10-20 pS in a 'physiological' K+ gradient. When
      added to the external solution at concentrations ranging between 1 and 200
      microM, phenytoin decreased single channel activity, whereas the unitary current
      amplitude was unaffected in all three types of channels. The open probability of
      the biggest channel decreased, according to an exponential distribution of open
      and closed times, from 40% in control conditions to 10% in the presence of 50
      microM phenytoin (Vm=40 mv). The reduction in the open-channel probability was
      concentration-dependent with a IC50 = 27.2+/-0.9 microM. A transient type of K
      channel was identified that was affected by cumulative inactivation and had a
      conductance of a mean value equal to 26 pS. Finally, a voltage-and Ca2+-dependent
      K+ channel with a unitary conductance of 95 pS was recorded. Both the channel's
      amplitude and kinetics were unaffected by phenytoin. These results confirm the
      phenytoin effect on K+ currents and suggest that the drug may be considered a
      selective blocker of delayed rectifier K+ channels.

PMID- 9756387
TI  - Evidence that tachykinins are the main NANC excitatory neurotransmitters in the
      guinea-pig common bile duct.
AB  - Application of electrical field stimulation (EFS; trains of 10 Hz, 0.25 ms pulse
      width, supramaximal voltage for 60 s) to the guinea-pig isolated common bile duct
      pretreated with atropine (1 microM), produced a slowly-developing contraction
      ('on' response) followed by a quick phasic 'off' contraction ('off peak'
      response) and a tonic response ('off late' response), averaging 16+/-2, 73+/-3
      and 20+/-4% of the maximal contraction to KCl (80 mM), n=20 each, respectively.
      Tetrodotoxin (1 microM; 15 min before) abolished the overall response to EFS (n
      8). Neither in vitro capsaicin pretreatment (10 microM for 15 min), nor
      guanethidine (3 microM, 60 min before) affected the excitatory response to EFS (n
      5 each), showing that neither primary sensory neurons, nor sympathetic nerves
      were involved. Nomega-nitro-L-arginine (L-NOARG, 100 microM, 60 min before) or
      naloxone (10 microM, 30 min before) significantly enhanced the 'on' response
      (294+/-56 and 205+/-25% increase, respectively; n=6-8, P<0.01) to EFS. The
      combined administration of L-NOARG and naloxone produced additive enhancing
      effects (655+/-90% increase of the 'on' component, n = 6, P<0.05). The tachykinin
      NK2 receptor-selective antagonist MEN 11420 (1 microM) almost abolished both the
      'on' and 'off late' responses (P<0.01: n=5 each) to EFS, and reduced the 'off
      peak' contraction by 55+/-8% (n=5, P<0.01). The subsequent administration of the
      tachykinin NK1 receptor-selective antagonist GR 82334 (1 microM) and of the
      tachykinin NK3 receptor-selective antagonist SR 142801 (30 nM), in the presence
      of MEN 11420 (1 microM), did not produce any further inhibition of the response
      to EFS (P>0.05; n=5 each). At 3 microM, GR 82334 significantly reduced (by 68+/
      9%, P<0.05, n=6) the 'on' response to EFS. The contractile 'off peak' response to
      EFS observed in the presence of both MEN 11420 and GR 82334 (3 microM each) was
      abolished (P<0.01; n=6) by the administration of the P2 purinoceptor antagonist
      pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 30 microM). PPADS
      (30 microM) selectively blocked (75+/-9 and 50+/-7% inhibition, n = 4 each) the
      contractile responses produced by 100 and 300 microM ATP. Tachykinin-containing
      nerve fibres were detected by using immunohistochemical techniques in all parts
      of the bile duct, being distributed to the muscle layer and lamina propria of
      mucosa. In the terminal part of the duct (ampulla) some labelled ganglion cells
      were observed. In conclusion, this study shows that in the guinea-pig terminal
      biliary tract tachykinins, released from intrinsic neuronal elements, are the
      main NANC excitatory neurotransmitters, which act by stimulating tachykinin NK2
      (and possibly NK1) receptors. ATP is also involved as excitatory
      neurotransmitter. Nitric oxide and opioids act as inhibitory mediators/modulators
      in this preparation.

PMID- 9756388
TI  - MS-551 and KCB-328, two class III drugs aggravated adrenaline-induced
      arrhythmias.
AB  - We investigated the proarrhythmic effects of MS-551 and KCB-328, class III
      antiarrhythmic drugs using adrenaline-induced arrhythmia models in halothane
      anaesthetized, closed-chest dogs. In the control period, adrenaline, starting
      from a low dose of 0.25 to up to 1.0 microg/kg/50 s i.v., was injected to
      determine the arrhythmia inducing dose and the non-inducing dose. After MS-551 or
      KCB-328 administration, the adrenaline injection was repeated and the interval
      between the injection and the occurrence of arrhythmia (latent interval), the
      changes in arrhythmic ratio (as calculated by dividing the number of ventricular
      premature contraction by the number of the total heart rate) and the severity of
      arrhythmia were observed. MS-551 infusion, 1 mg/kg/30 min, decreased the heart
      rate (HR) by 16% (P<0.01) and prolonged the QTc interval by 20% (P<0.01). During
      the 30 min of MS-551 infusion, arrhythmias occurred in three out of seven dogs
      (torsades de pointes (TdP) type VT in one dog). After these arrhythmias
      disappeared, MS-551 decreased the latent interval of the adrenaline arrhythmias
      produced by the inducing dose (30+/-2 s compared with 43+/-3 s of the control
      interval, P < 0.05), increased the arrhythmic ratio (P<0.05) and induced
      arrhythmias by non-inducing adrenaline doses (P<0.05). Effect of a new class III
      drug KCB-328 infusion, 0.3 mg/kg/30 min, was compared witih MS-551 using the same
      model. KCB-328 decreased the HR by 21% (P<0.01) and prolonged the QTc interval by
      25% (P<0.01). During the 30 min of infusion, arrhythmias occurred in five out of
      seven dogs (TdP in two dogs). KCB-328 also decreased the latent interval of the
      adrenaline arrhythmias produced by the inducing doses (31+/-3 s compared with
      49+/-7 s of the control period, P<0.05), but did not significantly alter the
      arrhythmic ratio. Adrenaline induced TdP only after MS-551 or KCB-328 was
      administered, i.e. after MS-551, 1 mg/kg/30 min, 3/7 versus 0/7 in the control;
      KCB, 0.3 mg/kg/30 min, 3/7 versus 0/7 in the control. To examine the direct
      arrhythmogenic effect of MS-551 and whether an adrenergic mechanism plays some
      role on this arrhythmogenesis, a bolus injection of MS-551, 3 mg/kg, was injected
      either without pre-treatment or after pre-treatment with propranolol 0.3 mg/kg.
      MS-551 induced arrhythmias in five out of seven dogs (TdP in one dog). Also in
      the propranolol pre-treated dogs, MS-551 induced arrhythmias in five out of seven
      dogs (TdP in 1 dog). In conclusion, these observations indicate that MS-551 and
      KCB-328 induced arrhythmias and intensified proarrhythmic effects of adrenaline,
      MS-551 being stronger than KCB-328 at the same QTc prolonging doses. The direct
      arrhythmogenic effect of MS-551 was not influenced by beta-blocker treatment.

PMID- 9756389
TI  - Modulation of IL-1-induced cartilage injury by NO synthase inhibitors: a
      comparative study with rat chondrocytes and cartilage entities.
AB  - Nitric oxide (NO) is produced in diseased joints and may be a key mediator of IL
      1 effects on cartilage. Therefore, we compared the potency of new [aminoguanidine
      (AG), S-methylisothiourea (SMT), S-aminoethylisothiourea (AETU)] and classical
      [Nomega-monomethyl-L-arginine (L-NMMA), Nomega-nitro-L-arginine methyl ester (L
      NAME)] NO synthase (NOS) inhibitors on the inhibitory effect of recombinant human
      interleukin-1beta (rhIL-1beta) on rat cartilage anabolism. Three different
      culture systems were used: (1) isolated chondrocytes encapsulated in alginate
      beads; (2) patellae and (3) femoral head caps. Chondrocyte beads and cartilage
      entities were incubated in vitro for 48 h in the presence of rhIL-1beta with a
      daily change of incubation medium to obtain optimal responses on proteoglycan
      synthesis and NO production. Proteoglycan synthesis was assessed by incorporation
      of radiolabelled sodium sulphate [Na2(35)SO4] and NO production by cumulated
      nitrite release during the period of study. Chondrocytes and patellae, as well as
      femoral head caps, responded concentration-dependently to IL-1beta challenge (0
      to 250 U ml(-1) and 0 to 15 U ml(-1) respectively) by a large increase in nitrite
      level and a marked suppression of proteoglycan synthesis. Above these
      concentrations of IL-1beta (2500 U ml(-1) and 30 U ml(-1) respectively),
      proteoglycan synthesis plateaued whereas nitrite release still increased thus
      suggesting different concentration-response curves. When studying the effect of
      NOS inhibitors (1 to 1000 microM) on NO production by cartilage cells stimulated
      with IL-1beta (25 U ml(-1) or 5 U ml(-1)), we observed that: (i) their ability to
      reduce nitrite level decreased from chondrocytes to cartilage samples, except for
      L-NMMA and AETU; (ii) they could be roughly classified in the following rank
      order of potency: AETU > L-NMMA > or = SMT > or = AG > or = L-NAME and (iii) AETU
      was cytotoxic when used in the millimolar range. When studying the effect of NOS
      inhibitors on proteoglycan synthesis by cartilage cells treated with IL-1beta, we
      observed that: (i) they had more marked effects on proteoglycan synthesis in
      chondrocytes than in cartilage samples; (ii) they could be roughly classified in
      the following rank order of potency: L-NAME > or = L-NMMA > > AG > SMT > > AETU
      and (iii) potentiation of the IL-1 effect by AETU was consistent with
      cytotoxicity in the millimolar range. D-isomers of L-arginine analog inhibitors
      (1000 microM) were unable to correct nitrite levels or proteoglycan synthesis in
      IL-1beta treated cells. L-arginine (5000 microM) tended to reverse the correcting
      effect of L-NMMA (1000 microM) on proteoglycan synthesis, thus suggesting a NO
      related chondroprotective effect. However, data with L-NAME and SMT argued
      against a general inverse relationship between nitrite level and proteoglycan
      synthesis. Dexamethasone (0.1 to 100 microM) (i) failed to inhibit NO production
      in femoral head caps and chondrocytes beads whilst reducing it in patellae (50%)
      and (ii) did not affect or worsened the inhibitory effect of IL-1beta on
      proteoglycan synthesis. Such results suggested a corticosteroid-resistance of rat
      chondrocyte iNOS. Data from patellae supported a possible contribution of
      subchondral bone in NO production. In conclusion, our results suggest that (i) NO
      may account only partially for the suppressive effects of IL-1beta on
      proteoglycan synthesis, particularly in cartilage samples; (ii) the
      chondroprotective potency of NOS inhibitors can not be extrapolated from their
      effects on NO production by joint-derived cells and (iii) L-arginine analog
      inhibitors are more promising than S-substituted isothioureas for putative
      therapeutical uses.

PMID- 9756390
TI  - Involvement of ET(A) and ET(B) receptors in the activation of phospholipase D by
      endothelins in cultured rat cortical astrocytes.
AB  - This study was performed to characterize the receptor subtypes involved in the
      endothelin stimulation of phospholipase D (PLD) in rat cortical astrocytes in
      primary culture. PLD activity was determined by measuring the formation of
      [32P]phosphatidylbutanol in [32P]orthophosphate prelabelled cells stimulated in
      the presence of 25 mM butanol. The agonists endothelin-1 (ET-1), endothelin-3 (ET
      3), sarafotoxin 6c (S6c) and IRL 1620 elicited PLD activation in a concentration
      dependent manner. The potencies of ET-1, ET-3 and S6c were similar. The maximal
      effects evoked by the ET(B)-preferring agonists, ET-3, S6c and IRL 1620, were
      significantly lower than the maximal response to the non-selective agonist ET-1.
      The response to 1 nM ET-1 was inhibited by increasing concentrations of the ET(A)
      receptor antagonist BQ-123 in a biphasic manner. A high potency component of the
      inhibition curve (24.2+/-3.5% of the ET-1 response) was defined at low (up to 1
      microM) concentrations of BQ-123, yielding an estimated Ki value for BQ-123 of
      21.3+/-2.5 nM. In addition, the presence of 1 microM BQ-123 significantly reduced
      the maximal response to ET-1 but did not change the pD2 value. Increasing
      concentrations of the ET(B) selective antagonist BQ-788 inhibited the S6c
      response with a Ki of 17.8+/-0.8 nM. BQ-788 also inhibited the effect of ET-1,
      although, in this case, two components were defined, accounting for approximately
      50% of the response, and showing Ki values of 20.9+/-5.1 nM and 439+/-110 nM,
      respectively. The ET-1 concentration-response curve was shifted to the right by 1
      microM BQ-788, also revealing two components. Only one of them, corresponding to
      69.8+/-4.4% of the response, was sensitive to BQ-788 which showed a Ki value of
      28.8+/-8.9 nM. Rapid desensitization was achieved by preincubation with ET-1 or
      S6c. In cells pretreated with S6c neither ET-3 nor S6c activated PLD, but ET-1
      still induced approximately 40% of the response shown by non-desensitised cells.
      This remaining response was insensitive to BQ-788, but fully inhibited by BQ-123.
      In conclusion, endothelins activate PLD in rat cortical astrocytes acting through
      both ET(A) and ET(B) receptors, and this response desensitizes rapidly in an
      apparently homologous fashion. The percentage contribution of ET(A) and ET(B)
      receptors to the ET-1 response was found to be approximately 20% and 80%,
      respectively, when ET(B) receptors were not blocked, and 30-50% and 50-70%,
      respectively, when ET(B) receptors were inhibited or desensitized. These results
      may be relevant to the study of a possible role of PLD in the proliferative
      effects shown by endothelins on cultured and reactive astrocytes.

PMID- 9756391
TI  - Depolarization counteracts glucocorticoid inhibition of adenohypophysical
      corticotroph cells.
AB  - In AtT20 mouse corticotroph tumour cells large conductance Ca2+-activated K+
      channels (BK-channels) have an essential role in the early glucocorticoid
      inhibition of adrenocorticotrophin (ACTH) secretion evoked by corticotrophin
      releasing factor. The present study examined whether or not BK-channels are also
      pivotal to glucocorticoid inhibition of normal rat anterior pituitary cells. A
      membrane-permeant, non-metabolizable cyclic AMP analogue, 8-(4
      Chlorophenylthio)adenosine-3',5'-cyclic-monophosphate (CPT-cAMP) was used as the
      primary secretagogue stimulus, as this mimics the increase of intracellular
      cyclic AMP caused by corticotrophin-releasing factor, but is not subject to the
      complex Ca2+-dependent regulation of cyclic AMP metabolism that is evident in
      corticotroph cells. Experiments in AtT20 cells showed that ACTH secretion
      stimulated by 1 mM CPT-cAMP was suppressed to 34+/-1.5% (n = 12) of the control
      stimulus by a maximal dose of 100 nM dexamethasone. The ACTH secretion evoked by
      the combination of 1 mM CPT-cAMP with either 5 microm (-)BayK8644 (L-type Ca2+
      channel activator) or 5 mM TEA (K+-channel blocker) was respectively 69.1+/-7.6%
      and 69.3+/-11.8% of control after 2 h preincubation with 100 nM dexamethasone
      (P<0.05 vs CPT-cAMP). The ACTH response elicited by 5 microM (-)BayK8644 and 5 mM
      TEA given together was completely resistant to inhibition by 100 nM
      dexamethasone. Furthermore, TEA and (-)BayK8644 given together synergistically
      stimulated ACTH release in combination with 0.1 mM or 1 mM CPT-cAMP, and these
      ACTH responses were not inhibited by 100 nM dexamethasone. In primary cultures of
      rat anterior pituitary cells, TEA (up to 20 mM), charybdotoxin (30 nM) or apamin
      (100 nM) failed to modify the glucocorticoid inhibition of 0.1 mM CPT-cAMP
      induced ACTH release. The combination of 5 mM TEA and 5 microM (-)BayK8644
      elicited a small but significant increase in ACTH secretion but did not modify
      the inhibition of 0.3 mM CPT-cAMP-induced ACTH secretion by 100 nM dexamethasone.
      In primary cultures of rat anterior pituitary cells, depolarization of the
      membrane potential with 40 mM KCl enhanced the ACTH response to CPT-cAMP and
      markedly reduced the maximal inhibitory effect of dexamethasone to 55+/-1.2% as
      well as that of corticosterone to 33+/-2.1% vs 100+/-2.5% and 100+/-1.9%
      inhibition respectively, when 0.1 mM CPT-cAMP was used alone. Introduction of 5
      microM (-)BayK8644 with 40 mM KCl in this system had no additional effect on
      glucocorticoid inhibition. No glucocorticoid inhibition of ACTH release to any of
      the stimuli applied was observed in cells pretreated with the mRNA synthesis
      inhibitor, 5,6-dichloro-furanosyl-benzimidazole riboside (DRB) (0.1 mM) or the
      protein synthesis blocker, puromycin (0.1 mM). In summary, early glucocorticoid
      inhibition of stimulated ACTH release by cultured rat anterior pituitary cells
      was dependent on the synthesis of new mRNA and protein. Depolarization of the
      membrane potential potentiated CPT-cAMP-induced ACTH secretion in AtT20 cells as
      well as cultured rat corticotrophs and this was associated with a resistance to
      the early inhibitory effect of glucocorticoids. Glucocorticoid inhibition in rat
      anterior pituitary corticotrophs was unaltered by TEA, charybdotoxin as well as
      apamin, and hence it is unlikely to involve predominantly BK-or SK-type Ca2+
      activated K+-channels. These results support the thesis that a prime target of
      glucocorticoid feedback inhibition in anterior pituitary corticotrophs is the
      membrane potential and indicate that glucocorticoid-induced proteins regulate the
      activities of several distinct plasma membrane ion channels.

PMID- 9756393
TI  - Calcium influx inhibition by steroids and analogs in C2C12 skeletal muscle cells.
AB  - Glucocorticoids, namely alpha-methylprednisolone (PDN) and deflazacort, are the
      only drugs reported to have a beneficial effect on the degenerative course of
      Duchenne muscular dystrophy (DMD). Increased cytosolic calcium concentrations
      ([Ca2+]c) have been implicated as one of the pathological events responsible for
      the degeneration of dystrophic skeletal muscles. In previous studies, we have
      demonstrated that PDN treatment of both normal and dystrophic murine skeletal
      muscle cells was able to normalize elevated [Ca2+]c and improved myogenesis. Here
      we have investigated the mechanism underlying the effects of glucocorticoids on
      cellular Ca2+ influx into C2C12 skeletal muscle cells. Long-term incubation of
      C2C12 myocytes with PDN was necessary to observe a reduction of 45Ca2+ influx.
      PDN was most effective in inhibiting 45Ca2+ uptake when added for 4 days (at the
      time of fusion of myoblasts into myotubes) and to a lesser extent, when added
      after fusion. It was ineffective when added to C2C12 cells at the myoblast stage.
      Short PDN incubation times, at the time of fusion were insufficient to elicit a
      response. Several steroids were tested for their ability to inhibit 45Ca2+ influx
      in C2C12 myocytes. All four glucocorticoids examined were able to reduce Ca2+
      influx, dexamethasone being the most potent (IC50 3.14+/-0.34 x 10(-8) M).
      Mineralocorticoids (aldosterone and 11-deoxycorticosterone) were also able to
      reduce Ca2+ influx. The vitamin E-derived lazaroid U-83836E and the
      glucocorticoid-derived lazaroid U-74389G also elicited a decrease in Ca2+ influx,
      but higher concentrations were necessary. Because both glucocorticoids and
      lazaroids display antioxidant properties, but U-83836E is devoid of
      glucocorticoid activity, the reduction in Ca2+ influx was suspected to be
      triggered via an antioxidant mechanism. To test this hypothesis, we assessed the
      action of several antioxidants, such as vitamin E, vitamin C, 2-tert.-butyl-4
      methoxyphenol (BHA), 2,6-di-tert.-butyl-4-methyl-phenol (BHT) and
      nordihydroguaiaretic acid (NDGA), on 45Ca2+ influx. None of these agents had an
      effect on 45Ca2+ influx. In addition, several oxidants were tested (either
      acutely or chronically) for their ability to elicit 45Ca2+ influx in C2C12
      myocytes and were found to be inactive. The involvement of the glucocorticoid
      receptor on the modulation of Ca2+ influx was investigated. The glucocorticoid
      receptor antagonist mifepristone (code name RU38486, 10(-6) M) caused a shift of
      two orders of magnitude of the PDN response. However, neither actinomycin D nor
      cycloheximide affected the response to PDN. Results with the phospholipase A2
      inhibitor, manoalide, suggest that glucocorticoid-induced protein synthesis (e.g.
      enhanced stimulation of lipocortin) does not play a role in the reduction of
      calcium influx. Our results suggest that steroids elicit a decrease in calcium
      influx in C2C12 skeletal muscle cells. This decrease is not due to an antioxidant
      mechanism or to a mechanism which requires gene expression. Since
      mineralocorticoids and U-83836E also had similar effects, the mechanism could
      belong to the non-genomic effects of corticoids (e.g. membrane stabilization).
      The beneficial effect of glucocorticoids in DMD could be attributed to a
      reduction of the pathological increase in Ca2+ influx via an effect on the
      sarcolemma.

PMID- 9756392
TI  - Histamine H1-receptor-mediated increase in the Ca2+ transient without a change in
      the Ca2+ current in electrically stimulated guinea-pig atrial myocytes.
AB  - The effects of histamine on the intracellular Ca2+ concentration ([Ca2+]i),
      action potential and membrane currents were assessed in single atrial myocytes
      prepared from guinea-pigs. Histamine caused a concentration-dependent increase in
      the [Ca2+]i transient in indol/AM loaded myocytes when stimulated electrically at
      0.5 Hz. However, the maximum increase in [Ca2+]i transient produced by histamine
      was less than 50% of that elicited by isoprenaline. The histamine-induced
      increase in [Ca2+]i transient was significantly inhibited by chlorpheniramine,
      but not by cimetidine. Pretreatment with nifedipine nearly completely suppressed
      the histamine-induced increase in [Ca2+]i transient. Cyclopiazonic acid did not
      affect the histamine response. In the whole-cell current-clamp mode of the patch
      clamp method, both histamine and isoprenaline prolonged action potential duration
      (APD) in atrial myocytes. In the presence of Co2+ or nifedipine, the isoprenaline
      induced APD prolongation was abolished and an APD shortening effect was
      manifested, while histamine still increased APD. The APD prolongation elicited by
      histamine was reversed by chlorpheniramine. In the voltage-clamp mode, the
      histamine-sensitive membrane current was inwardly rectifying and reversed close
      to the calculated value of the K+ equilibrium potential. Histamine had no
      apparent effect on L-type Ca2+ current, in contrast to the pronounced effect of
      isoprenaline. These results indicate that in guinea-pig atrial myocytes
      stimulation of H1-receptors with histamine does not directly activate Ca2+
      channels but causes an elevation of [Ca2+]i transient by increasing Ca2+ influx
      through the channels during the prolonged repolarization of action potentials
      resulting from inhibition of the outward K+ current.

PMID- 9756394
TI  - Inhibitors of the activity of poly (ADP-ribose) synthetase reduce the cell death
      caused by hydrogen peroxide in human cardiac myoblasts.
AB  - Poly (ADP-ribose) synthetase (PARS) is a nuclear enzyme activated by strand
      breaks in DNA which are caused by reactive oxygen species (ROS). Inhibitors of
      PARS activity reduce the degree of reperfusion injury of the heart in vivo and in
      vitro. Here we investigate the role of PARS in the cell death of human cardiac
      myoblasts caused by hydrogen peroxide. Exposure of human cardiac myoblasts to
      hydrogen peroxide caused a time- and concentration-dependent reduction in
      mitochondrial respiration (cell injury), an increase in cell death (LDH release),
      as well as an increase in PARS activity. The PARS inhibitors 3-aminobenzamide (3
      mM), 1,5-dehydroxyisoquinoline (300 microM) or nicotinamide (3 mM) attenuated the
      cell injury and death as well as the increase in PARS activity caused by hydrogen
      peroxide (3 mM; 4 h for cell injury/death, 60 min for PARS activity) in human
      cardiac myoblasts. In contrast, the inactive analogues 3-aminobenzoic acid (3 mM)
      or nicotinic acid (3 mM) were without effect. The iron chelator deferoxamine (1
      10 mM) caused a concentration-dependent reduction in the cell injury and death
      caused by hydrogen peroxide in these human cardiac myoblasts. Thus, the cell
      injury/death caused by hydrogen peroxide in human cardiac myoblasts is secondary
      to the formation of hydroxyl radicals and due to an increase in PARS activity. We
      therefore propose that activation of PARS contributes to the cell injury/cell
      death associated with oxidant stress in the heart.

PMID- 9756395
TI  - L-687,414, a low efficacy NMDA receptor glycine site partial agonist in vitro,
      does not prevent hippocampal LTP in vivo at plasma levels known to be
      neuroprotective.
AB  - N-methyl-D-aspartic acid (NMDA) receptors are known to play a key role in the
      induction phase of long-term potentiation (LTP) at certain hippocampal synapses
      and to represent some component of spatial learning in animals. The ability of
      NMDA receptor antagonists (or gene knockout) to impair LTP has led to the
      suggestion that the therapeutic use of such antagonists may impair cognitive
      function in humans. The present study compares the effects on LTP of NMDA
      receptor ion channel block by MK-801 and glycine-site antagonism by 3R(+)cis-4
      methyl-pyrrollid-2-one (L-687,414). In vitro experiments using rat cortical
      slices revealed L-687,414 to be approximately 3.6 fold more potent than its
      parent analogue, R(+)HA-966 at antagonizing NMDA-evoked population
      depolarizations (apparent Kbs: 15 microM and 55 microM, respectively). Whole-cell
      voltage-clamp experiments using rat cultured cortical neurones revealed L-687,414
      to shift to the right the concentration-response relationship for NMDA-evoked
      inward current responses (pKb=6.2+/-0.12). L-687,414 affinity for the glycine
      site on the NMDA receptor complex was also determined from concentration
      inhibition curves, pKi=6.1+/-0.09. In the latter experiments, L-687,414 and
      R(+)HA-966 were unable to completely abolish inward current responses suggesting
      each compound to be a low efficacy partial agonist (estimated intrinsic activity
      = approximately 10 and 20% of glycine, respectively). L-687,414 and MK-801 were
      compared for their effects on NMDA receptor-dependent LTP in the dentate gyrus of
      anaethestized rats following high frequency stimulation of the medial perforant
      path (mPP) afferents. Control rats, administered saline (0.4 ml kg(-1) followed
      by 0.0298 ml min(-1)), showed a robust augmentation of the population e.p.s.p.
      risetime (LTP) recorded in the dentate hilus following tetanic stimulation of the
      mPP. LTP was effectively abolished in a separate group of rats treated with an MK
      801 dosing regimen (0.12 mg kg(-1) i.v. followed by 1.8 microg kg(-1) h(-1))
      known to produce maximal neuroprotection in a rat stroke model but, by contrast,
      remained largely intact in a third group of animals given a similarly
      neuroprotective L-687,414 treatment (28 mg kg(-1) i.v. followed by 28 mg kg(-1)
      h(-1)). These experiments suggest that a low level of intrinsic activity at the
      glycine site may be sufficient to support NMDA receptor-dependent LTP but in
      circumstances where there is likely to be an excessive NMDA receptor activation
      the agonism associated with a low efficacy partial agonist, such as L-687,414, is
      dominated by the antagonist properties. Thus, an NMDA receptor partial agonist
      profile may offer a therapeutic advantage over neutral antagonists by permitting
      an acceptable level of 'normal' synaptic transmission whilst curtailing excessive
      receptor activation.

PMID- 9756396
TI  - Biphasic effects of cyclosporin A on formyl-methionyl-leucyl-phenylalanine
      stimulated responses in HL-60 cells differentiated into neutrophils.
AB  - The immunosuppressive drug cyclosporin A (CsA) depresses neutrophil oxidative
      burst which may lead to an increased susceptibility to infection in transplant
      patients. Using specific CsA analogues we investigated the mechanism of
      inhibition of the oxidative burst and evaluated short and long-term effects of
      CsA on dimethylsulphoxide-differentiated HL-60 neutrophils. A biphasic pattern
      was observed: a 4 h pre-treatment with CsA (1 microM) diminished the fMLP induced
      [Ca2+]c rise, reactive oxygen species (ROS) production, and beta-glucuronidase
      release by about 40%, whereas a 20 h pre-treatment increased these responses by
      about 1.5 fold. [MeVal4]CsA, which binds with high affinity to cyclophilin but
      inhibits the interaction of the CsA-cyclophilin complex with calcineurin, blocked
      the stimulation observed with CsA after a 20 h incubation but did not alter the
      CsA effects after a 4 h pre-treatment. PSC 833 (1 microM), a potent multi drug
      resistance transporter (MDR) inhibitor, diminished ROS production to the same
      extent as a 4 h CsA incubation but was ineffective after a 20 h pre-treatment. An
      involvement of MDR as a basis for CsA or PSC 833 action was ruled out based on
      the results of the calcein retention assay. [3H]CsA uptake showed that CsA and
      [MeVal4]CsA, but not CsH or PSC 833 were strongly taken up and retained by the
      cells. In conclusion, the reduction of the responses after 4 h appear to be due
      to a primary reduction of calcium signalling, while the enhanced responses after
      20 h may be due to calcineurin inhibition.

PMID- 9756397
TI  - Citalopram-induced hypophagia is enhanced by blockade of 5-HT(1A) receptors: role
      of 5-HT(2C) receptors.
AB  - The selective 5-hydroxytryptamine reuptake inhibitor citalopram (10 and 20 mg kg(
      1), i.p.) significantly reduced food intake in male rats (CD-COBS) habituated to
      eat their daily food during a 4-h period. The 5-HT1A receptor antagonist
      WAY100635 (0.3 mg kg(-1)) administered systemically did not modify feeding but
      significantly potentiated the reduction in food intake caused by 10 mg kg(-1)
      i.p. citalopram. The dose of 5 mg kg(-1) i.p. citalopram was not active in
      animals pretreated with vehicle but significantly reduced feeding in animals
      pretreated with WAY100635. WAY100635 (0.1 microg 0.5 microl(-1)) injected into
      the dorsal raphe significantly potentiated the hypophagic effect of 10 mg kg(-1)
      citalopram. WAY100635 (1.0 microg 0.5 microl(-1)) injected into the median raphe
      did not modify feeding or the hypophagic effect of 10 mg kg(-1) citalopram. The 5
      HT2B/2C receptor antagonist SB206553 (10 mg kg(-1), p.o.) slightly reduced
      feeding by itself but partially antagonized the effect of WAY100635 administered
      systemically (0.3 mg kg(-1), s.c.) or into the dorsal raphe (0.1 microg 0.5
      microl(-1)) in combination with 10 mg kg(-1) i.p. citalopram. The hypophagic
      effect of 10 mg kg(-1) i.p. citalopram alone was not significantly modified by
      SB206553. Brain concentrations of citalopram and its metabolite
      desmethylcitalopram in rats pretreated with SB206553, WAY100635 and their
      combination were comparable to those of vehicle-pretreated rats, 90 min after
      citalopram injection. The hypophagic effect of citalopram was potentiated by
      blocking 5-HT1A receptors. Only the effect of the WAY100635/citalopram
      combination seemed to be partially mediated by central 5-HT2C receptors.

PMID- 9756398
TI  - Involvement of CD44 exon v10 in B-cell activation.
AB  - The family of CD44 glycoproteins has been suggested to be involved in lymphocyte
      homing, maturation and activation. Using in vitro blocking studies with a
      monoclonal antibody, we here addressed the question of functional activity of
      CD44 variant exon v10 (CD44v10) in B-cell activation. We became interested in
      this question by the observation that CD44v10O was transiently expressed on
      activated T cells, B cells and monocytes as well as on a subpopulation of bone
      marrow cells. A potential ligand, as revealed by staining with a CD44v10 receptor
      globulin, was only detected on monocytes. Anti-CD44v10 had no major impact on T
      cell activation and no influence on primed B cells, but interfered with the
      mounting of a primary B-cell response to T-independent and T-dependent antigens.
      Addition of anti-CD44v10 at different stages during the activation process
      revealed that CD44v10 was not engaged in B-cell-T-cell interactions. The antibody
      exerted some effect on monocyte activation as defined by a slight decrease in IL
      1 production, but most efficiently inhibited antigen-specific as well as mitogen
      induced B-cell activation when present during the coculture of virgin B cells
      with monocytes. These findings, together with the observation that a CD44v10
      ligand was only detected on monocytes but not on lymphocytes, point towards a
      requirement for CD44v10 in a B-cell-monocyte interaction. Furthermore, since
      activation of B cells by engagement both of the B-cell receptor and of mitogen
      receptors was inhibited by anti-CD44v10, the data suggest that a costimulatory
      function of CD44v10 proceeds independent of the B-cell receptor.

PMID- 9756399
TI  - High frequency of altered HLA class I phenotypes in invasive colorectal
      carcinomas.
AB  - We analyzed the expression of HLA class I antigens in 78 tumor tissue samples
      obtained from patients diagnosed as having colorectal carcinomas. A broad panel
      of mAbs defining HLA monomorphic, locus-specific and allele-specific determinants
      was used. In addition, an antibody defining HLA-C locus-specific determinant
      (L31) was also tested. Previous reports on these tumors indicated HLA class I
      losses of 30 to 40%. At least 73% of the patients in the present study had a
      detectable HLA class I alteration. These altered HLA phenotypes were classified
      as total HLA loss (18%) (phenotype I); HLA-A locus-specific loss (9%) (phenotype
      IIIa); HLA-B locus-specific loss (8%) (phenotype IIIb); HLA-A and B locus losses
      (2%) and HLA allelic losses (36%) (phenotype IV). We found no HLA-C locus losses.
      Autologous peripheral blood lymphocyte HLA class I typing was always necessary to
      define phenotype IV. We also studied the CD3 zeta chain in tumor tissues to
      correlate possible changes in the CD3 signal transduction pathway with HLA
      alterations. The CD3 ratio was frequently altered, but this alteration could not
      be correlated with tumor HLA phenotypes. The high frequency of HLA class I losses
      in colorectal carcinomas suggests that this finding is a widespread phenomenon
      and may be required to escape T-cell recognition. It remains to be determined
      whether HLA expression is "normal" in the rest of the 27% of our patients.

PMID- 9756400
TI  - HLA and alveolar echinococcosis.
AB  - Evidence in animal intermediate hosts that susceptibility to larval infection
      with Echinococcus multilocularis is restricted to individual host factors
      prompted us to investigate the susceptibility markers in humans. Because antigens
      of the extracellular parasite E. multilocularis are possibly presented by MHC
      molecules in a restricted way, we speculated that MHC polymorphism may influence
      resistance of the host towards infection and course of disease. We studied HLA-A,
      -B, -DRB1, -DQB1 and -DPB1 polymorphism in 151 patients with alveolar
      echinococcosis. Patients with an observation period of more than 2 years were
      grouped according to the clinical follow-up into cured (no recurrence following
      surgery) patients and patients with regressive or progressive forms of disease
      during benzimidazole chemotherapy. By comparing phenotypic frequency between
      patients with alveolar echinococcosis and healthy controls, HLA-DRB1*11 was
      associated with a reduced risk for disease development (odds ratio=0.55, 95%
      confidence interval=0.34-0.88; P=0.01). HLA-DQB1*02 was more frequent in patients
      with progressive disease when compared with patients with regressive disease
      (54.3% vs 28.3%, P=0.02). The result suggests that HLA-DRB1*11 might confer
      protection against alveolar echinococcosis and that HLA-DQB1*02 may indicate a
      risk for progressive disease development. The findings may facilitate the search
      for immunodominant T-cell epitopes of E. multilocularis.

PMID- 9756401
TI  - HLA-DRB and -DQB1 alleles in Polish patients with hepatitis B associated
      membranous nephropathy.
AB  - We have studied the HLA-DRB and -DQB1 alleles of 42 paediatric patients who have
      suffered from membranous nephropathy associated with a hepatitis B infection
      (HBVMN). These patients were all from the Gdansk area of Northern Poland and the
      disease was diagnosed by light and electron microscopy. The control population
      consisted of 55 healthy children, approximately age matched, from schools in
      Gdansk. In addition we have also analysed 40 patients chronically infected with
      hepatitis B, without any renal involvement, as hepatitis B disease controls. The
      HLA alleles were defined using PCR/SSP. As idiopathic membranous nephropathy and
      low responsiveness to hepatitis B vaccine have been found to be associated with
      DR3 in Caucasoids, our hypothesis was that the HBVMN patients would show an
      increase in DR3. Our results indicate that, although there is a small increase in
      the frequency of DRBl*0301 in the HBVMN patients (16/42 38%) when compared to the
      healthy controls (15/55 31%), this does not approach significance. There is a
      significant increase in the frequency of DQB1*0303 in the HBVMN patients vs the
      healthy controls, after correction for the number of antigens detected (Pc)(13/42
      vs 2/55, RR=11.6, P=0.0007, Pc=0.02). A similar increase in DQB1*0303 is seen in
      the HBVMN patients when compared to the hepatitis controls (13/42 vs 4/40) but
      this is only significant before correction (RR=4.3, P=0.04).

PMID- 9756402
TI  - HLA polymorphisms in Italian bone marrow donors: a regional analysis.
AB  - The aim of this study was to analyse the genetic structure of the Italian bone
      marrow donor population on the basis of HLA polymorphisms. Maximum likelihood
      estimates of gene and haplotype frequencies, goodness of fit to Hardy-Weinberg
      predictions and heterozygosity were calculated for 18 Italian administrative
      regions. Moreover, the phenotypic peculiarity of the regional populations was
      assessed by analysing the number of "typical phenotypes" found in each region.
      Multivariate analyses carried out on HLA-A and HLA-B gene frequencies gave a
      genetic pattern of the donor pools that reflects the structure of the Italian
      population determined in previous population genetic studies. Sardinia shows a
      very large genetic difference with respect to the other regions; of these, the
      central-southern regions are well-differentiated from the central-northern.
      Southern regions present higher genetic heterogeneity and a higher probability of
      providing donors with phenotypes not already present in the Italian bone marrow
      registry. The large sample size of the bone marrow donor registry allowed us to
      estimate gene and haplotype frequencies with greater accuracy than in previous
      studies. Our results may be of use in determining strategies for donor
      recruitment and selecting unrelated donors for patients requiring bone marrow
      grafting, as well as for anthropological, epidemiological and population genetics
      studies.

PMID- 9756403
TI  - Diversity of HLA-DR2 in North Indians: the changed scenario after the discovery
      of DRB1*1506.
AB  - DRB1*1506, a new allele of DR2, differs from DRB1*1501 only at codon 50 in the
      second exon, where the nucleotide sequence has changed from GTG to GCG resulting
      in an amino acid substitution from valine to alanine in DRB1*1506. Since codon 50
      was considered non-polymorphic until the discovery of this new allele by sequence
      based typing, it became necessary to study what fraction of subjects thought to
      have DRB1*1501 actually had DRB1*1506. For this purpose, 116 DNA samples with DR2
      coming from normal healthy individuals, leprosy patients and childhood
      tuberculosis patients were amplified using PCR and hybridized with 32P-labeled
      probes specific for DRB1*1501, DRB1*1502, DRB1*1503, DRB1*1506, DRB1*1601 and
      DRB1*1602. The oligonucleotide probe for DRB1*1506 was designed to span codons 47
      52 based on the published nucleotide sequence. DRB5, DQA1 and DQB1-specific
      amplifications and hybridizations were also carried out to study the diversity of
      DR2 haplotypes. It was found that 21% of the samples identified previously as
      DRB1*1501 were actually DRB1*1506. DRB1*1506 was found to be associated with
      DQB1*0502 and DQB1*0601. Haplotypes of DRB1*1501, DRB1*1502, DRB1*1506 and
      DRB1*1602 showed a marked heterogeneity. Besides the rare haplotypes which have
      not yet been reported in any other populations, haplotypes characteristic of
      different ethnic groups, such as Croatians, South Chinese and Gypsies, were also
      found in the North Indians, suggesting the extent of racial admixture and
      migrations to and from India.

PMID- 9756404
TI  - Polymorphism and distribution of HLA-DR2 alleles and haplotypes in a Greek
      population.
AB  - HLA-DR2 serological subtyping has indicated that the DR16 serotype appears at a
      higher frequency relative to the DR15 serotype in the Greek population, differing
      from the distribution observed in most other Caucasian groups. In this study, we
      have analyzed by the PCR-SSP technique a DR2-positive group of unrelated Greek
      individuals selected from our normal control panel for the different DRB1, DRB5,
      DQB1 and DQA1 DR2-associated alleles present. Six of the 50 individuals analyzed
      were homozygous for DR2, contributing a total of 56 haplotypes for DR2. The
      observed frequencies of the DR2-related DRB1 alleles were as follows: 58.9% for
      the DRB1*1601, 7.1% for the DRB1*1602, 25.0% for the DRB1*1501 and 7.1 % for the
      DRB1*1502 allele. The rare allele DRB1*1605 was detected in one heterozygous
      sample and its presence was definitively established by DNA sequencing. The
      alleles *1503, *1504, *1505, *1603 and *1604 were not detected. Three DRB5
      alleles were identified: DRB5*0202 (67.8%), DRB5*0101 (25.0%) and DRB5*0102
      (7.1%). Ten different DRB1/DQB1/ DQA1 DR2-associated haplotypes were defined. The
      most frequently observed haplotype was DRB1*1601-DQB1*0502-DQA1*0102 (relative
      frequency=57%) followed by DRB1*1501-DQB1*0602-DQA1*0102 (relative
      frequency=14.3%). In conclusion, the refined analysis of the DR2-associated DRB1
      alleles in the Greek population revealed the prevalence of the DRB1*1601 allele.
      The rare allele DRB1*1605 was demonstrated once. A considerable variety of
      different DR2-related DR/DQ haplotypes was detected and the overall haplotypic
      frequencies in the Greek population are distributed differently compared to those
      reported for most other Caucasian populations.

PMID- 9756405
TI  - The PCR-SSP Manager computer program: a tool for maintaining sequence alignments
      and automatically updating the specificities of PCR-SSP primers and primer mixes.
AB  - An emerging problem of molecular typing methods such as PCR amplification using
      sequence-specific primers (PCR-SSP) is that they frequently require updating as
      new alleles are constantly being described which potentially affect the
      specificity of every PCR-SSP reaction. PCR-SSP uses pairs of primers to detect
      cis-linked polymorphisms and thus each new allele described must be compared to
      each individual primer pair. Furthermore, sequence homology between the various
      loci for class I and class II means that, for example, new HLA-A sequences have
      to be compared with HLA-B and HLA-C primer mixes to rule out cross-locus
      amplification. We have developed a computer program known as SSP Manager which is
      capable of aligning HLA class I and class II sequences obtained from Internet
      accessible databases such as GenBank. The program then updates all individual
      primer specificities held in its database before updating the specificities of
      all primer mixes. Sets of primer mixes can then be combined from the primer mix
      directory to create PCR-SSP typing trays which are subsequently analysed by the
      program. A report is generated which stipulates whether all known sequences are
      amplified and the reason for apparent failure to test for individual alleles,
      e.g. a lack of relevant sequence information. SSP Manager has the flexibility to
      cope with unusual sequences (deletions and insertions), primers with internal
      mismatches and primers with a deliberate mismatch. The program also has many
      tools for developing new primer mixes, such as the facility to search for novel
      reactions using Boolean operators. The organisation and operational use of the
      SSP Manager program is described and its uses are illustrated with an updated
      allele list for our previously described Phototyping PCR-SSP class I and class II
      typing set. The SSP Manager is available on request from the authors.

PMID- 9756406
TI  - HLA-B*27 typing by group-specific hybridization in microtiter plates.
AB  - We have developed and evaluated a test for HLA-B*27 based on PCR and DNA
      hybridization in microtiter plates. A region within exon 2 of the HLA-B gene is
      amplified and labeled by PCR and the amplification product is hybridized to a
      group-specific HLA-B*27 and a generic control oligonucleotide probe in two
      separate cavities of the plate. Bound sequences are detected using an ELISA-like
      protocol. The assay has been evaluated on 254 DNA samples routinely received for
      B27 testing in parallel with serological and SSP-PCR typing. Results were
      concordant in typing 102 HLA-B27-positive and 152 HLA-B27-negative individuals
      except for two samples containing HLA-B*73, which stained B27 positive in the
      microwell test. The new procedure is rapid and simple to perform, and the
      microwell format is particularly suitable for automation.

PMID- 9756407
TI  - HLA-DP-associated susceptibility to the optico-spinal form of multiple sclerosis
      in the Japanese.
AB  - We studied polymorphism of the HLA-DP gene in 46 patients with optico-spinal form
      (Asian type) multiple sclerosis (MS) showing recurrent opticomyelitis and 46
      patients with Western type MS with disseminated central nervous system
      involvement. We previously reported a significant association between an HLA-DRB1
      *1501-DRB5*0101 haplotype and susceptibility to Western type but not Asian type
      MS. In the present study, we found that the frequencies of DPA1 *0202 and DPB1
      *0501 alleles were significantly increased in patients with Asian type MS, as
      compared with findings in 92 healthy control subjects (91.3% vs 65.2%,
      P(corr)<0.05 and 89.1% vs 63.0%, P(corr)<0.05 respectively), but not in Western
      type MS. Our data provide further evidence that Asian and Western type MS are
      distinct regarding the immunogenetic background.

PMID- 9756408
TI  - Characterization and distribution of HLA-B*5002 in a Spanish population sample.
AB  - HLA-B45, in contrast to B44, does not show molecular polymorphism. We have found
      a group of Caucasian Spanish individuals, serologically typed as B45, showing an
      unexpected HLA-B12 PCR-SSO subtyping pattern. Complete coding region sequencing
      and B45 subtyping by PCR-SSO demonstrated that the B45 serologic specificity is
      constituted by two molecular alleles: B*4501 and B*5002. B*5002 is recognized by
      polyclonal and monoclonal allosera against B12 and B45, whereas it is not
      detected by B21, B49, or B50 reagents, providing a new example of poor
      correlation between serology and structure. B*5002 explains an important subset
      (18%) of the B45-positive individuals of the Spanish population studied, and
      almost half are included in a very infrequent haplotypic association, Cw6-B*5002
      DRB1*0406-DQA1*03-DQB1*0402.

PMID- 9756409
TI  - Novel polymorphism detected in exon 1 of HLA-B*2713.

PMID- 9756410
TI  - Identification of two new DPB1 alleles, DPB1*7701 and *7801, by sequence-based
      typing.

PMID- 9756411
TI  - Identification of a new DPB1 allele (DPB1*7901) by sequence-based typing.

PMID- 9756412
TI  - Nucleotide sequencing reveals a novel DQB1-06 allele (DQB1*06013) with a silent
      mutation at codon 137.

PMID- 9756413
TI  - Limited importance of CD40/CD40L interaction in the B7-dependent generation of
      anti-MOPC-315 cytotoxic T lymphocyte activity by tumor bearer splenic cells
      stimulated in vitro in the presence of tumor necrosis factor.
AB  - We have previously illustrated the importance of B7-2 expression for the enhanced
      generation of cytotoxic T lymphocyte (CTL) activity by stimulation cultures of
      tumor bearer splenic cells to which tumor necrosis factor alpha (TNFalpha) has
      been added. Here we show that the B7-1 molecule is also important for CTL
      generation by such stimulation cultures, although to a much lesser extent than
      the B7-2 molecule. In addition, we show the importance of CD40/CD40L interaction
      for the expression of the B7-2 molecule, but not the B7-1 molecule, by tumor
      bearer splenic cells stimulated in vitro in the presence of TNF. The CD40/CD40L
      interaction is also shown to be important for the generation of CTL activity by
      tumor bearer splenic cells stimulated in vitro in the presence of exogenous TNF.
      However, the CD40/CD40L interaction is less important for the generation of
      enhanced CTL activity than for the expression of an elevated level of B7-2.
      Specifically, blockade of CD40/CD40L interaction, which reduced the level of B7-2
      expressed by tumor bearer splenic cells stimulated in vitro in the presence of
      TNF to the level of B7-2 expressed by tumor bearer splenic cells stimulated in
      vitro in the absence of exogenous TNF, failed to reduce the level of CTL
      generated to the level generated by tumor bearer splenic cells stimulated in the
      absence of exogenous TNF. Finally, blockade of CD40/CD40L interaction was
      inferior to blockade of B7-2/CD28 interaction in inhibiting the generation of CTL
      activity by tumor bearer splenic cells stimulated in the presence of exogenous
      TNF. Thus, although CD40/CD40L interaction is important for the generation of
      enhanced CTL activity by stimulation cultures of tumor bearer splenic cells to
      which TNF has been added, TNF also mediates its potentiating effect for CTL
      generation by such stimulation cultures via other mechanisms that are independent
      of CD40/CD40L interaction but dependent on B7-2 expression.

PMID- 9756414
TI  - Human tumor cells, modified by a novel pressure/crosslinking methodology, promote
      autologous lymphocyte proliferation and modulate cytokine secretion.
AB  - Hydrostatic pressure (P) combined with membrane protein crosslinking (CL) by
      adenosine dialdehyde (AdA) can render tumor cells immunogenic. We have recently
      shown that PCL treatment of murine tumor cells augmented the presentation of MHC
      restricted tumor-associated antigens and enhanced cell-mediated immunity. In
      cancer patients inoculated with autologous PCL-modified tumor cells, a
      significant delayed-type hypersensitivity response was elicited. Since the
      balance between cell-mediated immunity and humoral immunity is reciprocally
      controlled by immunoregulatory cytokines, we have examined the proliferative
      response and cytokine secretion pattern in cultures of human peripheral blood
      mononuclear cells (PBMC) stimulated by autologous PCL-modified and unmodified
      tumor cells. These tumor cells were obtained from freshly resected tumor tissue
      of 16 patients with colon (8), lung (4) and renal (4) carcinomas. The results
      demonstrated that PCL-modified tumor cells promoted an increase in PBMC
      proliferation in 5 out of 8 (63%), 1 out of 4 (25%) and 4 out of 4 (100%) colon,
      lung and renal cell carcinomas. Fourteen of the above cultures were also analyzed
      for the secretion of interleukin-10 and interferon-gamma. Overall, a substantial
      decrease in IL-10 secretion was detected in 9 out of 14 (64%) cultures while a
      reciprocal increase in interferon-gamma secretion was noted in 8 out of 14 (57%)
      cultures. Our results confirmed that PCL-modified human tumor cells of different
      etiologies can modulate the pattern of cytokines released from stimulated
      autologous lymphocytes. Such a procedure could prove valuable in the production
      of autologous tumor vaccines.

PMID- 9756415
TI  - Antibody-dependent difference in biodistribution of monoclonal antibodies in
      animal models and humans.
AB  - The study was designed to clarify the difference in pharmacokinetics of
      monoclonal antibodies (mAb) in animal models and humans, and to elucidate the
      applicability of animal models. 99mTc-labeled murine mAb -- against
      carcinoembryonic antigen (designated BW431/26), and neural cell adhesion molecule
      (NE150) -- and one chimeric mouse/human mAb against nonspecific cross-reacting
      antigen (chNCA) were administered i.v. to normal mice and athymic mice (370 kBq,
      400 ng) xenografted with human cancer cells expressing antigens, and into
      patients with tumor (925 MBq, 1 mg). The biodistribution of two of the three mAb
      (not 99mTc-BW431/26) differed clearly in mice and patients. 99mTc-NE150 showed
      specific uptake in xenografted tumor and otherwise a normal biodistribution;
      however, clinical examination showed increased uptake in the liver with rapid
      blood clearance (mean alpha half-life = 31.1 min) compared with 99mTc-BW431/26
      (28.4 h). 99mTc-chNCA demonstrated increased blood clearance and renal excretion
      in both normal and athymic mice, with accumulation in tumors. Clinical
      examination showed rapid blood clearance (mean alpha half-life = 6.4 min) and
      increased uptake in the liver. High-performance liquid chromatographic analysis
      of 99mTc-chNCA revealed the immune complex in blood, suggesting uptake of the
      complex by the reticuloendothelial cells. The biodistribution of radiolabeled mAb
      in animal and human models was variable and specific for each of the three mAb.
      The results of animal studies with mAb should be evaluated carefully before being
      extrapolated to humans, on the basis of the nature of the mAb and interacting
      substances.

PMID- 9756416
TI  - Evaluation of natural killer cell expansion and activation in vivo with daily
      subcutaneous low-dose interleukin-2 plus periodic intermediate-dose pulsing.
AB  - Natural killer (NK) cells may be expanded in vivo with a prolonged course of
      daily subcutaneous interleukin-2 (IL-2). However, cellular activation requires
      higher concentrations of IL-2 than are achieved with low-dose therapy. The
      objective of the current trial was to determine the toxicity and immunological
      effects of periodic subcutaneous intermediate-dose IL-2 pulses in patients
      receiving daily low-dose therapy. A group of 19 patients were treated with daily
      subcutaneous low-dose IL-2 at 1.25 x 10(6) International Units (1.25 MIU) m(-2)
      day(-1). After 4-6 weeks, patients received escalating 3-day intermediate-dose IL
      2 pulses administered as single daily subcutaneous injections, repeated at 2-week
      intervals. The maximum tolerated pulse dose was 15 MIU m(-2) day(-1), with
      transient hypotension, fatigue, and nausea/vomiting dose-limiting. Subcutaneous
      IL-2 resulted in in vivo expansion of CD56+ NK cells (796+/-210%) and CD56bright
      natural killer (NK) cells (3247+/-1382%). Expanded NK cells coexpressed CD16, and
      showed lymphokine-activated killer activity and antibody-dependent cellular
      cytotoxicity in vitro. Intermediate-dose pulsing resulted in serum IL-2
      concentrations above 100 pM. Cellular activation was suggested by rapid
      margination of NK cells following pulsing, coincident with peak IL-2 levels, with
      return to baseline by 24 h. In.addition, interferon gamma production in response
      to lipopolysaccharide was augmented. Subcutaneous daily low-dose IL-2 with
      intermediate-dose pulsing is a well-tolerated outpatient regimen that results in
      in vivo expansion and potential activation of NK cells, with possible application
      in the treatment of malignancy and immunodeficiency.

PMID- 9756417
TI  - Transcription factor activation in lymphokine activated killer cells and
      lymphocytes from patients receiving IL-2 immunotherapy.
AB  - Administration of the cytokine interleukin-2 (IL-2) can result in therapeutic
      benefits for individuals with renal cell carcinoma and melanoma. Here we report
      an analysis of the transcription factor families AP-1, Sp1, NF-kappaB, and signal
      transducers and activators of transcription (STAT) in cancer patients'
      lymphocytes before and after IL-2 immunotherapy, as assessed by a gel-shift
      assay. An in vitro surrogate of IL-2 immunotherapy is the incubation of fresh
      peripheral blood mononuclear cells (PBMC) from healthy individuals in IL-2 for
      several days, resulting in the production of lymphokine-activated killer (LAK)
      activity in these cultures. One purpose of this study was to describe the profile
      of transcription factor activation in these different populations, and assess
      whether the patterns observed correlated with functional differences in these
      cells. Prior to in vivo IL-2 administration, the typical binding pattern of
      transcription factors in PBMC from patients resembled that seen in fresh PBMC
      from healthy individuals. Over a 3-week course of IL-2 therapy, in most patients
      the binding patterns of AP-1 , Sp1, and NF-kappaB proteins changed to resemble
      those seen in PBMC activated by IL-2 in vitro. However, the cells obtained from
      IL-2-treated patients did not have low-level constitutive expression of STAT
      binding factors as did LAK cells. When these patient cells were further
      stimulated by IL-2 in vitro, additional differences in STAT induction patterns
      were noted. These data provide further information on the molecular events
      occurring in immune cells generated through in vivo and in vitro administration
      of IL-2, and further document that there is not a precise congruence between PBMC
      activated in vivo and in vitro by IL-2.

PMID- 9756418
TI  - Polysaccharide K induces Mn superoxide dismutase (Mn-SOD) in tumor tissues and
      inhibits malignant progression of QR-32 tumor cells: possible roles of interferon
      alpha, tumor necrosis factor alpha and transforming growth factor beta in Mn-SOD
      induction by polysaccharide K.
AB  - Previously we reported the malignant progression of QR-32, a regressor-type tumor
      clone, following co-implantation with foreign bodies (gelatin sponge or plastic
      plate) in normal syngeneic C57BL/6 mice. We also reported that the progression of
      QR-32 cells by a gelatin sponge was significantly inhibited in the mice
      administered polysaccharide K (PSK) and that PSK induced an increase of radical
      scavengers, especially manganese superoxide dismutase (Mn-SOD), locally at the
      site of tumor tissues. In this study, to reveal the possible mechanism by which
      PSK induced Mn-SOD in the tumor tissues, we examined the mRNA expression and
      protein levels of inflammatory cytokines in the tissues. We found that mRNAs of
      tumor necrosis factor alpha (TNFalpha) and interleukin-1alpha (IL-1alpha) were
      considerably expressed in both PSK-treated and phosphate-buffered-saline-treated
      tumors, and that the mRNA expression and protein level of interferon gamma
      (IFNgamma) increased in the tumor tissues treated with PSK. In vitro treatment of
      QR-32 cells with IFNgamma did not significantly increase the production of Mn
      SOD; however, the combination of IFNgamma with TNFalpha increased the Mn-SOD
      production more effectively than did any of the cytokines used singly.
      Furthermore, we observed the down-regulation of the mRNA expression and protein
      level of transforming growth factor beta (TGFbeta) in the tumor tissues treated
      with PSK, and that in vitro treatment of QR-32 cells with TGFbeta decreased the
      production of Mn-SOD. These results suggest that PSK suppresses the progression
      of QR-32 cells by increasing Mn-SOD via the modulation of inflammatory cytokines;
      that is, by decreasing TGF-beta and increasing IFN-gamma.

PMID- 9756419
TI  - Serum anti-p53 autoantibodies in primary resected non-small-cell lung carcinoma.
AB  - Mutated p53 proteins accumulate in the nuclei of tumor cells, and anti-p53
      autoantibodies are found in the sera of patients with non-small-cell lung
      carcinoma (NSCLC). We analyzed the correlation among serum anti-p53
      autoantibodies, immunohistochemical staining for p53, and clinical features (age,
      gender, smoking history, histological type, differentiation, stage, T factor,
      tumor size, and N factor) in resected non-small-cell lung carcinomas. A total of
      62 cases of resected NSCLC were studied (43 men and 19 women; 33 adenocarcinomas,
      21 squamous cell carcinomas, 8 large-cell carcinomas). Preoperative serum titers
      of anti-p53 autoantibodies were detected in 13/62 cases (21.0%). A correlation
      between histological type and positive titers of serum p53 autoantibodies was
      seen (large-cell carcinoma versus squamous cell carcinoma and adenocarcinoma, P =
      0.031, chi2-test). Out of 25 cases, 10 (40%) with positive immunohistochemical
      staining for p53 had positive titers, whereas 3 positive titers were found in 37
      patients with negative immunohistochemical staining for p53 (P = 0.0025, chi2
      test). Serum titers of anti-p53 autoantibodies were present in approximately 20%
      of the cases of NSCLC, and overexpression of p53 protein in tumor cells was
      detectable in approximately 40%. Serum anti-p53 autoantibodies may be a clinical
      parameter for the presence of p53 mutations and p53 overexpression in NSCLC
      patients.

PMID- 9756420
TI  - Relationship between immune state and tumor growth rate in rats bearing
      progressive and non-progressive mammary tumors.
AB  - Impaired immune responses occur frequently in cancer patients or in tumor-bearing
      animals, but the mechanisms of the tumor-induced immune defects remain poorly
      understood. The aim of the present study was to determine the relevance of the
      immune system in the control of tumor growth. We have developed a model of
      progressive and non-progressive mammary tumor, chemically induced in female
      Wistar rats. In this model we evaluated the development of an immune response
      after immunization of rats bearing progressive and non-progressive tumors with a
      non-related antigen, such as sheep red blood cells. We also studied the
      activation state of peritoneal macrophages from animals bearing tumors by
      evaluating the production of free radicals. Our findings indicated that the cell
      mediated immunity in rats bearing progressive tumors fails to respond to
      heterologous antigen in vivo, as demonstrated by a negative delayed-type
      hypersensitivity reaction, and is accompanied by minor nitric oxide production by
      peritoneal exudate cells as well as a lower capacity for macrophage activation.
      The study of non-progressive tumor-bearing rats indicated that the cell-mediated
      immune response was intact and an activated state of macrophages was found in
      vivo. The results described in this paper should be taken into account when
      therapies based on cancer vaccines are chosen for the treatment of cancer.

PMID- 9756421
TI  - Noninvasive investigations in vascular disease. St Mary's Fellows. ISVI (Italian
      Society for Vascular Investigations).

PMID- 9756422
TI  - Diagnosis of renovascular disease by extra- and intrarenal Doppler parameters.
AB  - It is still a matter of debate as to which parameters should be used for
      noninvasive diagnosis of renovascular disease by renal Doppler sonography (RDS).
      The accuracy of RDS in the detection of renal artery stenosis (RAS) was tested in
      95 consecutive, moderate to severe hypertensive patients (I-II World Health
      Organization [WHO] stages). Reno-aortic ratio (RAR) for peak systolic velocity
      (PSV) was also calculated to assist in the diagnosis of significant (>50%) RAS.
      Paired receiver-operating characteristic (ROC) analysis was plotted for
      evaluating the relationship between sensitivity and specificity for each
      parameter. In a subset of 57 kidneys, the influence of blood pressure and age on
      intraparenchymal parameters was evaluated. Measurements of maximal peak systolic
      velocity (PSV) at the site of stenosis, RAR for PSV, and minimum acceleration
      index in the main renal artery showed high accuracy (areas under the ROC curve
      0.97, 0.88, and 0.80, respectively). Among intraparenchymal parameters, early
      systolic acceleration showed the best area under the ROC curve (0.90), but
      provided a low positive predictive value (29%) and was significantly influenced
      by blood pressure (multiple r=0.56; p=0.001). Pulsatility and resistive indices
      were found to be less powerful as absolute values, and both significantly
      influenced by blood pressure and age (multiple r=0.60 and 0.50; p=0.001, p=0.02,
      respectively). However, interindividual variance of intrarenal indices should be
      minimized by calculation of side difference, although this procedure would become
      misleading or impossible in patients with bilateral RAS or a single kidney,
      respectively. These results support the use of extraparenchymal parameters for
      noninvasive detection of RAS, and emphasize that intrarenal parameters cannot be
      considered as absolute values.

PMID- 9756423
TI  - Comparison of three blood pressure methods used for determining ankle/brachial
      index in patients with intermittent claudication.
AB  - The standard noninvasive test to assess the severity of peripheral arterial
      occlusive disease (PAOD) is the ankle/brachial systolic blood pressure index
      (ABI). While ankle systolic blood pressure is obtained by the Doppler ultrasound
      technique, brachial systolic blood pressure can be obtained by the Doppler,
      auscultatory, or oscillometric (Dinamap 1846 SX) methods. The purpose was to
      determine whether the three methods yielded similar brachial systolic blood
      pressure values, and consequently similar ABI values, in PAOD patients with
      intermittent claudication. Fifty patients who had a history of intermittent
      claudication of 2.3 +/- 2.0 blocks for a duration of 5.7 +/- 5.8 years were
      recruited. Following 10 minutes of supine rest, brachial systolic blood pressure
      was measured in the right arm by the three techniques in a randomized order, and
      ankle systolic blood pressure (87.3 +/- 28.9 mmHg) was measured in the more
      symptomatic leg with the Doppler technique. Brachial systolic blood pressure was
      not significantly different (p=0.954) among the Doppler (128.5 +/- 18.4 mmHg),
      auscultatory (128.4 +/- 17.4 mmHg), and oscillometric (128.2 +/- 17.1 mmHg)
      methods. Corresponding ABI values also were similar (p=0.922) among the three
      respective methods (0.68 +/- 0.22, 0.68 +/- 0.22, and 0.68 +/- 0.21), indicating
      that ABI did not vary according to the technique used to obtain brachial systolic
      blood pressure. It is concluded that the accuracy of determining ABI in PAOD
      patients with intermittent claudication was minimally affected by the method
      chosen to obtain brachial systolic blood pressure.

PMID- 9756424
TI  - Venoarteriolar response to experimental venous hypertension in legs with chronic
      venous insufficiency and in healthy legs, measured using a double-wavelength
      laser Doppler technique.
AB  - The venoarteriolar response (VAR) of the skin in legs caused by experimental
      venous hypertension was measured using a new, double-wavelength laser Doppler
      probe technique (543 nm and 780 nm). This enables the measurement of the laser
      Doppler flux in the superficial and deep layers of the skin simultaneously. The
      recordings were obtained from the leg with the patient in a recumbent position
      with a sphygmomanometer cuff around the thigh. The VAR was recorded at the cuff
      pressures of 30 mmHg and 60 mmHg. Ten patients with chronic venous insufficiency
      (CVI) and 20 control subjects with healthy legs were investigated. The VAR
      increased in relation to the increase of cuff pressure at both wavelengths. There
      were no significant differences in the VAR between the cuff pressures within or
      between the legs with CVI and healthy legs. The VAR measured at 780 nm was very
      significantly greater than the VAR measured at 543 nm in legs with CVI (p<0.005),
      as well as in healthy legs (p<0.001). The VAR depends both on the wavelength of
      the laser Doppler light used and on the degree of venous hypertension. The VAR is
      not impaired in legs with CVI compared with healthy legs.

PMID- 9756425
TI  - Gas tensions in cardiac lymph as a reflection of the interstitial space of the
      heart.
AB  - The purpose of this study was to determine the feasibility of measuring partial
      pressure of oxygen (pO2), partial pressure of carbon dioxide (pCO2), and pH in
      cardiac lymph and to evaluate the relationship of these parameters to comparable
      measurements in arterial and coronary sinus blood in the normal heart under
      various respiratory conditions. In four anesthetized open-chest dogs, the
      principal cardiac lymphatic as well as the femoral artery and coronary sinus were
      cannulated. Ventilation was varied by changing oxygen concentration, tidal
      volume, and respiratory rate. PO2, pCO2, and pH were measured in the cardiac
      lymph, arterial blood, and coronary sinus blood after each change in ventilation.
      For pH and pCO2, good correlations were observed between the arterial blood and
      cardiac lymph, arterial blood and coronary sinus blood, and coronary sinus blood
      and cardiac lymph. The correlation between the pO2 measured in the arterial blood
      and the pO2 measured in the cardiac lymph was not as strong, and this may have
      been related to difficulty achieving a steady state. Gas tensions (pO2, pCO2, and
      pH) can be measured in cardiac lymph and may provide a window to the interstitial
      compartment of the heart. This is an additional tool for the laboratory study of
      ischemia and other forms of heart disease.

PMID- 9756427
TI  - Effect of physical activity on the distensibility of the aortic wall in healthy
      males.
AB  - To study the effect of physical activity level on the distensibility of the human
      aortic wall, aortic pulse wave velocity (APWV) was estimated in 139 healthy male
      subjects (19-67 years) and was related to the energy expenditure by habitual
      physical exercise (physical activity index: PAI), which was evaluated by a 7-day
      total activity recall. The subjects consisted of 56 fun runners (runner group)
      and 83 general subjects, who were divided into 25 active subjects (active group:
      PAI > or = 1,500 kcal/week) and 58 sedentary subjects (sedentary group: PAI <
      1,500 kcal/week). The APWV index (APWVI: standardized APWV by the diastolic blood
      pressure) was found to be positively correlated with age and was negatively
      correlated with PAI. The age-adjusted APWVI of the runner group was significantly
      lower than that of the active and sedentary groups. The age-adjusted APWVI was
      also significantly lower in the active group than in the sedentary group. These
      results suggest that increased physical activity may retard the age-dependent
      loss of arterial distensibility in humans, in proportion to the amount and/or
      intensity of exercise.

PMID- 9756426
TI  - Vasodilatory capacity of forearm resistance vessels is augmented in
      hypercholesterolemic patients after treatment with fluvastatin.
AB  - Atherosclerotic vessels are characterized by endothelial and structural
      abnormalities as indicated by an impaired vasodilation to metabolic requirements.
      To determine whether effective treatment of hypercholesterolemia may improve
      vasodilatory capacity of resistance vessels, the authors examined the impact of
      12 and 24 weeks of lipid-lowering therapy with the hepatic hydroxymethylglutaryl
      coenzyme A (HMG-CoA)-reductase inhibitor fluvastatin (40 to 80 mg/day) on the
      increment in forearm blood flow during reactive hyperemia in 24
      hypercholesterolemic patients (mean age: 56 +/- 11 years; 15 men/9 women).
      Changes in forearm blood flow in response to reactive hyperemia were measured by
      venous occlusion plethysmography. Serum low-density lipoprotein (LDL)-cholesterol
      fell from 213 +/- 32 to 125 +/- 27 mg/dL (P<0.001) after 12 weeks and remained
      stable at a level of 125 +/- 18 mg/dL after 24 weeks of treatment. Baseline
      forearm blood flow was similar before and after 12 and 24 weeks of therapy. In
      contrast, forearm blood flow at peak reactive hyperemia was greater at week 12
      (37.0 +/- 22.9 mL/min/100 mL; P<0.05), and at week 24 (47.1 +/- 33.5 mL/min/100
      mL; P<0.05) than at week 0 (30.5 +/- 18.1 mL/min/100 mL). Compared with week 0
      (defined as 100%), the percent change in forearm blood flow in response to
      reactive hyperemia was augmented at week 12 (171 +/- 144%; P<0.05 vs week 0) and
      at week 24 (218 +/- 228%; P<0.05 vs week 0). Thus, the lowering of high serum LDL
      cholesterol after short-term treatment with fluvastatin increased the blood flow
      responses during reactive hyperemia in forearm resistance vessels. These data
      indicate a beneficial effect of HMG-CoA reductase inhibition on structural wall
      properties of peripheral arteries in human atherosclerosis.

PMID- 9756428
TI  - Pulmonary embolism in patients with isolated soleal vein thrombosis.
AB  - This study investigated the features of calf deep vein thrombosis (DVT) as a
      pulmonary embolic source. Fifty-eight lower limbs in 29 patients who were
      suspected of having DVT distal to the popliteal vein were screened by
      ultrasonography. Then, ascending venography was performed to confirm the
      diagnosis. Pulmonary embolism (PE) was diagnosed in suspected patients by use of
      pulmonary perfusion scanning or pulmonary angiography. Venography revealed calf
      DVT in 33 limbs in 28 patients. Of 28 patients, six had symptomatic PE.
      Thrombosis was found in the muscle veins in 18 limbs, the trunk veins in 11, and
      both veins in four. Isolated single vein thrombosis was found in the soleal vein
      in 14 limbs (42%), the posterior tibial vein in eight, the peroneal vein in two,
      and the gastrocnemius vein in two. The overall percentage of soleal vein thrombi
      was 61%. All six patients with symptomatic PE had isolated soleal vein
      thromboses. Calf DVT was a pulmonary embolic source when isolated thrombosis of
      the large soleal vein was more than 7 mm in diameter. Soleal veins were the most
      frequent and important location of calf DVT, suggesting that these were an
      occasional embolic source of critical PE.

PMID- 9756429
TI  - Homocysteine associated hypercoagulability and disseminated thrombosis--a case
      report.
AB  - The authors report the occurrence of vascular occlusion due to
      hyperhomocysteinemia without significant underlying atherosclerotic disease. This
      unique observation supports the potential of hyperhomocysteinemia to induce
      thrombosis and the independence of the thrombosis from hyperhomocysteinemia's
      associated atherosclerosis. The case demonstrates the clinical relevance of the
      effects of hyperhomocysteinemia on the coagulation cascade. A 42-year-old woman
      who lacked signs of classic homocystinuria developed disseminated thrombosis with
      a 24-hour urine homocysteine concentration of 384 mg, twelve times the upper
      limit of normal. Thrombosis was present in the aortic arch and its major branches
      and in the mesenteric arteries and veins. A fatal stroke resulted from the
      thrombosis. Autopsy revealed minimal atherosclerotic disease and no complicated
      plaques. This case demonstrates an expanded role of hyperhomocysteinemia in
      clinically significant vascular occlusion. Serum homocysteine concentration
      determination may be a factor in the evaluation of a hypercoagulable state.
      Hyperhomocysteinemia should be considered when evaluating arterial or venous
      thrombosis in a young person regardless of whether atherosclerosis or other signs
      of abnormal homocysteine metabolism are present.

PMID- 9756430
TI  - Bilateral fistulas from the internal mammary arteries and the bronchial arteries
      to the pulmonary arteries--a case report.
AB  - A 78-year-old man was admitted to hospital with heart failure and chronic
      bronchitis. A computed tomographic scan of the chest incidentally demonstrated
      bilateral abnormal vessels near the left atrium. Selective angiography showed
      that both internal mammary arteries and bronchial arteries communicated with the
      pulmonary arteries bilaterally. The patient refused surgery and was discharged on
      medical therapy. This is the first reported case of bilateral fistulas between
      the internal mammary arteries and bronchial arteries and the pulmonary arteries.

PMID- 9756431
TI  - Long-term follow-up of severe central serous chorioretinopathy using indocyanine
      green angiography.
AB  - BACKGROUND: The severe types of central serous chorioretinopathy (CSC) have a
      chronic nature, suggesting that a pathological process persists subclinically.
      Indocyanine green (ICG) angiography recently revealed intrachoroidal dye leakage
      and its static nature in CSC. As the intrachoroidal dye leakage was suspected to
      be relevant to the disease process, the long-term persistence of intrachoroidal
      ICG leakage was examined in four patients of the severe types of CSC. METHODS:
      ICG angiography was performed periodically over more than three years in three
      patients and two years in one patient. One patient had CSC with bullous retinal
      detachment, and the other three had chronic CSC or diffuse retinal pigment
      epitheliopathy. RESULTS: Intrachoroidal ICG leakage persisted in all the
      patients. However, a change in location of persistent intrachoroidal leakage or
      disappearance of intrachoroidal leakage regardless of no progression of retinal
      pigment epithelial alteration was noted in one eye of two patients. CONCLUSIONS:
      Pathology causing intrachoroidal ICG leakage persisted subclinically for a long
      period. However, location and extent of the intrachoroidal leakage could change
      during a long-term follow-up period.

PMID- 9756433
TI  - Evaluation of laser sclerostomy fistulas using ultrasound biomicroscopy.
AB  - BACKGROUND: Laser sclerostomy is a relatively new technique in glaucoma surgery.
      Clinical examination, particularly of the intrascleral part of laser sclerostomy
      fistulas, is difficult. We performed ultrasound biomicroscopy (UBM) in order to
      determine, if it were possible to visualize fistulas. Moreover, it was the aim to
      investigate whether this imaging technique could provide additional information
      on fistula morphology. PATIENTS AND METHODS: Ten eyes of eight patients with
      chronic open angle glaucoma who had undergone erbium-YAG laser sclerostomy ab
      externo were examined using a UBM-probe with a 20 MHz transducer providing
      spatial resolution of approximately 80 microm. RESULTS: Radial scanning allowed
      visualization of the sclerostomy fistula in nine of ten eyes. The different
      functional state of sclerostomy fistulas correlated well to UBM findings. It was
      possible to image differences in the morphology of occluded and patent fistulas
      and to visualize the filtering pathway in functioning blebs. CONCLUSIONS:
      Ultrasound biomicroscopy allows imaging of laser sclerostomy fistulas. UBM and
      clinical findings correlated well in the majority of the patients we examined.
      The technique supplements clinical examination and in some cases may provide
      additional information.

PMID- 9756432
TI  - Ocular sarcoidosis in Kuwait with a review of literature.
AB  - OBJECTIVE: To study 18 cases of sarcoidosis, the hall mark of which was uveitis.
      SETTING: Referrals from peripheral eye clinics. PATIENTS: 18 patients with
      bilateral almost symmetric uveitis, negative Mantoux test and positive gallium
      scan were enrolled in the study. Preliminary bronchoscopy and bronchial lavage
      were not done due to social habits. RESULTS: Age ranged between 7-48 years with
      median 15 and mean 19 years. Although the patients were multinational, yet all of
      them were residents of Kuwait. A father and son were affected within 8 months
      period. 78% were strictly ocular, associated pulmonary and salivary gland
      affection 11% each. Sole anterior uveitis was found in 28%, associated with
      intermediate uveitis in 55% and with posterior in 16.6% of cases. Clinically
      detectable dry eyes associated 33% of cases. All our patients developed glaucoma
      which resolved with treatment of uveitis in 88% of them. Gallium uptake of the
      eye balls was found in 22%, of the lacrimal glands (panda sign) in 67%, and of
      the salivary glands or chest 11% each. Positive biopsy was found in 72%, 22% of
      which was conjunctival. Chest X-ray and SACE were positive in 11%. 61% had
      hypergammaglobulinaemia and all had negative ANA and RF. CONCLUSIONS: (1) 61% of
      ocular sarcoidosis presented below sarcoid age. (2) Multinationality together
      with father's and son's affection indicate a climatic or environmental insult in
      an already predisposed person. (3) Routine chest X-ray and SACE may not be
      adequate for diagnosis of ocular sarcoidosis. Gallium should be done in suspected
      cases. (4) Follow-up for prospects is emphasized.

PMID- 9756434
TI  - Intravenous acyclovir treatment for extensive herpetic keratitis in a liver
      transplant patient.
AB  - Herpetic infection is a common complication among immune suppressed patients
      following heart, kidney and bone marrow transplantations, in leukemia patients,
      in AIDS patients, and during treatment with cytotoxic drugs. In the cases
      described in the literature, oral acyclovir was recommended as a treatment for
      the acute infection, as well as for prophylaxis. Intravenous acyclovir is not a
      routine treatment for herpetic keratitis, but is recommended for cases of
      insufficient clinical response to oral treatment, and defective absorption of
      acyclovir by the gastrointestinal tract. We present a patient who underwent 4
      liver transplantations, was treated regularly with immunosuppressive drugs, and
      who developed extensive herpetic keratitis. The keratitis was resistant to both
      topical ointment and oral acyclovir treatment. Recovery was only achieved
      following the intravenous administration of acyclovir. We recommend intravenous
      acyclovir treatment at a very early stage for immune suppressed patients with
      extensive herpes simplex keratitis.

PMID- 9756435
TI  - Ocular echography in the prognosis of vitreous haemorrhage in type II diabetes
      mellitus.
AB  - PURPOSE: In this study, we have attempted to demonstrate the presence of various
      echographic parameters which could be associated with a non-spontaneous
      resorption of vitreous haemorrhage in type II diabetes mellitus and correlate
      these parameters with clinical outcome. SUBJECTS AND METHODS: We studied 297 eyes
      of 257 patients with diabetic retinopathy and vitreous haemorrhage without
      tractional macular retinal detachment ophthalmoscopically and echographically. Of
      the total eyes studied, a 3-month follow-up visit (including ultrasound) was
      available in 208 eyes. We retrospectively reviewed the medical records of each
      patient. RESULTS: The echographic parameters associated with non-resorption of
      the vitreous haemorrhage were: extramacular tractional retinal detachment,
      fibrovascular membranes and location of the haemorrhage within the subhyaloidal
      space (in contrast to within the intragel space). In addition, the duration of
      the vitreous haemorrhage and the presence of panretinal laser photocoagulation at
      the time of presentation with a vitreous haemorrhage influenced the resolution of
      the vitreous haemorrhage. We were also able to construct a logarithmic function
      that could be used to predict the prognosis of a vitreous haemorrhage in type II
      diabetes mellitus. CONCLUSIONS: When employed to evaluate vitreous haemorrhages
      in non-insulin-dependent diabetes mellitus, ocular ultrasound can provide useful
      prognostic information regarding the lack of resorption of vitreous haemorrhages
      in type II diabetics.

PMID- 9756436
TI  - Profiling of human leukocyte antigens in Eales' disease.
AB  - Eales' disease is a primary retinal perivasculitis of an undetermined etiology
      seen predominantly in the Indian subcontinent and rarely in the West. Strong HLA
      association has been proven in retinal vasculitis of Behcet's disease. HLA
      association of Eales' disease is unknown and therefore the present study was
      undertaken to determine the same. The frequency of 30 HLA antigens (9 HLA-A
      antigens, 10 HLA-B antigens, 3 HLA-C antigens, 7 HLA-DR antigens and 1 HLA-DQ
      antigen) was studied by standard micro-lymphocytotoxicity test in 57 patients
      with Eales' disease and 50 age and sex-matched normal persons as controls. Both
      the patients and controls underwent complete ocular and clinical examinations and
      laboratory investigations. Inflammatory diseases similar to Eales' disease were
      ruled out in the patients before they were enrolled. Statistically significant
      higher phenotype frequencies of HLA B5 (B51), DR1 and DR4 were observed among
      patients with Eales' disease as compared to controls. The gene frequency of HLA
      B5 (B51) in our group of patients and controls was comparable with other earlier
      studies in the Indian population. The finding of significant association of
      Eales' patients with positive disequilibrium ( ) haplotypes A3-B44 and A11-B12
      may be related to the development of this disease. The presence of the above HLA
      antigens may be indicative of predisposition to Eales' disease.

PMID- 9756438
TI  - LASIK: management of common complications. Laser in situ keratomileusis.
AB  - PURPOSE: To review common complications noted with LASIK. METHODS: Review of
      personal experience of the author with the procedure and work published in the
      literature. RESULTS: The most common complications of the LASIK procedure include
      flap irregularities, epithelium and other materials within the lamellar
      interface, irregular astigmatism, regular astigmatism, regression, and
      overcorrection. Infection is a rare but potentially serious complication.
      CONCLUSIONS: LASIK has impressive potential for the correction of myopia and
      hyperopia. Surgeons who perform the procedure must be familiar with recognition
      and treatment of potential complications of LASIK.

PMID- 9756437
TI  - Analysis of 24,444 surgical specimens accessioned over 55 years in an ophthalmic
      pathology laboratory.
AB  - PURPOSE: To summarize the pathologic diagnoses of a large number of surgically
      obtained specimens over an extended time period in a single ophthalmic pathology
      laboratory. METHODS: We analyzed the records of 24,444 surgically obtained
      specimens accessioned in the L.F. Montgomery Ophthalmic Pathology Laboratory,
      Emory University, Atlanta, GA between May 1941 and December 1995. Age, sex,
      topography, clinical procedure, and histologic diagnosis were entered into a
      database using the modified SNOMED coding system. The diagnosis of the surgically
      enucleated eyes were analyzed with respect to years of enucleation. RESULTS: The
      most common topographic area associated with a histologic diagnosis was the
      cornea (39.3%), followed by lens (16.0%), vitreous (12.0%), uvea (9.8%), eyelids
      (8.0%), conjunctiva (7.7%), retina (7.7%), and orbit (2.1%). The relative
      proportion of vitreous specimens has continuously increased and became the most
      common surgical specimen in 1995. The most common underlying disease of
      surgically enucleated eyes is trauma (40.9%), followed by ocular neoplasia
      (24.2%), 'surgical' diseases of the cornea, lens and retina including glaucoma
      (17.3%), vascular diseases (6.7%), and inflammatory conditions (6.7%). The
      relative frequency of trauma and ocular inflammation as a cause of enucleation
      decreased significantly (p < 0.05) over the time of the study period while the
      relative proportion of ocular neoplastic processes increased (p < 0.0001).
      CONCLUSIONS: The availability of new surgical techniques has caused a change in
      the relative frequencies of different ocular specimens submitted for histologic
      examination.

PMID- 9756439
TI  - Changing indications for penetrating keratoplasty: histopathology of 1,250
      corneal buttons.
AB  - PURPOSE: To analyze recent trends in the indications for penetrating
      keratoplasty. METHODS: After keratoplasty, 2,557 corneal buttons were sent to and
      analyzed in the ophthalmopathology laboratory of the University of Erlangen
      Nurnberg, Erlangen, Germany, between 1992 and 1996. Of these, 1,250 random
      corneal buttons were evaluated in this study. RESULTS: Histopathologic diagnoses
      were (a) keratoconus (20.9%), (b) corneal scarring after keratitis/trauma
      (20.4%), (c) pseudophakic/aphakic bullous keratopathy (17%), (d) regraft (15.5%),
      (e) Fuchs' corneal endothelial dystrophy (14.9%), (f) necrotizing/ulcerative
      keratitis (5.3%), and (g) corneal dystrophies (1.7%). CONCLUSION: Compared with a
      previous report from our laboratory (1964-1986), the relative frequencies of
      pseudophakic/aphakic bullous keratopathy, regraft, and Fuchs' dystrophy
      increased, whereas corneal scarring decreased. Keratoconus is now the most
      frequent indication for penetrating keratoplasty.

PMID- 9756440
TI  - Morphological and fluorophotometric analysis of the corneal endothelium after
      radial keratotomy.
AB  - PURPOSE: To evaluate the morphometric and fluorophotometric characteristics of
      corneal endothelium after an eight-incision radial keratotomy (RK). METHODS: A
      total of 43 eyes of 26 patients underwent RK and 44 eyes of 23 patients were used
      as age-matched controls. All patients underwent specular microscopic and
      fluorophotometric examinations. Endothelial cell density [(ECD), cells/mm2], mean
      cell area [(MCA), microm2], coefficient of variation (CV) for cell area, and
      percentage (%) of hexagonal cells were measured by specular microscopy. Cornea-to
      anterior chamber transfer coefficient (kc.ca, 10(-3) min(-1)) and corneal
      endothelial permeability (10(-4) cm/min) were measured by fluorophotometry.
      RESULTS: Morphometric and fluorophotometric characteristics were similar in both
      the RK and control groups. Among patients in the RK group, the size of optical
      zone and the depth of corneal incision did not affect postoperative endothelial
      morphology or permeability. Those who presented for postoperative examination
      later than 3 months compared with those presented within 3 months of RK had lower
      CV for cell area; 0.28 +/- 0.04, 0.23 +/- 0.04, and 0.23 +/- 0.03, a higher
      percentage of hexagonal cells; 64.7 +/- 8.0, 71.7 +/- 7.8, and 72.2 +/- 6.5, and
      lower permeability; 5.7 +/- 1.9. 4.5 +/- 0.9, and 5.2 +/- 1.1, at <3 months,
      between 3 and 6 months, and >6 months after RK, respectively (all p < 0.05). In
      the eight cases of anisometropia, the operated eyes had a lower ECD; 3,079 +/-
      429, and 3,217 +/- 495, a higher MCA; 330.6 +/- 48.1 and 317.6 +/- 50.5, and a
      higher endothelial permeability; 6.3 +/- 1.5 and 4.7 +/- 1.3 in the operated and
      unoperated eyes, respectively, at 3.4 months after RK (p < 0.05). CONCLUSION: RK
      induced a minimal acute and nonprogressive endothelial loss. The transient
      increase in permeability within 3 months may be due to a reversible endothelial
      dysfunction induced by RK.

PMID- 9756441
TI  - Topographic pattern and apex location of keratoconus on elevation topography
      maps.
AB  - PURPOSE: To compare topography pattern and apex location in elevation and axial
      curvature topographic maps of keratoconic corneas. METHODS: We prospectively
      evaluated 72 corneas of 42 patients who had one or more corneal findings of
      keratoconus with the elevation and axial curvature displays of the PAR Corneal
      Topography System (PAR-CTS) and 66 of these corneas with the axial curvature
      display of the Tomey Topographic Modeling System (TMS-1). Topography maps were
      evaluated for topography pattern and location of the cone apex. RESULTS: Axial
      curvature displays of the PAR-CTS and the TMS-1 showed good concordance in terms
      of topographic patterns (96% for right, 86% for left corneas) and apex locations
      of cones (92% for right, 80% for left corneas). On the other hand, low
      concordances were noted when comparing topographic patterns (35.3% for right,
      36.8% for left corneas) and apex locations (47% for right, 38% for left corneas)
      on curvature and elevation mode displays of PAR-CTS. Apices were found in the
      inferotemporal quadrant in 65% of corneas evaluated with the PAR-CTS. This
      distribution is significantly different from the apex location in axial curvature
      maps (p < 0.04). Twenty-nine percent of corneas that showed an apex on the axial
      curvature mode of the PAR-CTS had a normal pattern, without a detectable cone
      apex, on the elevation mode display. CONCLUSIONS: The results of this study
      clearly show the difference between elevation and curvature-based corneal
      topographic evaluation of keratoconus. Unlike axial curvature maps, the majority
      of apices on elevation maps are clustered in the inferotemporal quadrant. This
      new information about apex location in keratoconic corneas provided by elevation
      topography may have better diagnostic specificity than regional differences of
      curvature on axial curvature maps. Because elevation mapping shows the physical
      location of the cone, it may improve results of contact lens fitting and surgical
      management.

PMID- 9756442
TI  - Normal human corneal cell populations evaluated by in vivo scanning slit confocal
      microscopy.
AB  - PURPOSE: To analyze cellular populations in healthy human corneas. METHODS: The
      study group consisted of 58 eyes of 45 patients with normal corneas. The age
      distribution was 45 +/- 17 years (mean +/- SD; range, 20-84). Scanning slit
      confocal microscopy of the central corneas was performed. The images were
      analyzed visually for cell morphology, and the densities and areas of cells were
      measured. RESULTS: No statistically significant differences were measured in cell
      densities or cell areas of any corneal layer between female and male patients (p
      = 0.22-0.50) nor between right and left eyes (p = 0.16-0.45). The area of
      superficial epithelial cells was 913 +/- 326 microm2 (mean +/- SD; range, 518
      2,112), and the superficial epithelial cell density was 1,213 +/- 370 cells/mm2
      (mean +/- SD; range, 473-1,929). The area of basal epithelial cells was 177 +/-
      19 microm2 (mean +/- SD; range, 138-242), and the basal epithelial cell density
      was 5,699 +/- 604 cells/mm2 (mean +/- SD; range, 4,135-7,267). The average
      apparent keratocyte density was 1,058 +/- 217 cells/mm2 (mean +/- SD; range, 604
      1,599) in the anterior stroma, and 771 +/- 135 cells/mm2 (mean +/- SD; range, 493
      1,145) in the posterior stroma. The difference in apparent keratocyte densities
      between the anterior and posterior stroma was statistically significant (p <
      0.001). The average endothelial cell area was 334 +/- 51 microm2 (range, 273
      553), and the cell density was 3,055 +/- 386 cells/mm2 (mean +/- SD; range, 1,809
      3,668). The endothelial cell density had a negative, statistically significant
      correlation with age (r = -0.68, p < 0.001). The densities of the other corneal
      cell layers did not have a statistically significant correlation with age.
      CONCLUSION: In vivo scanning slit confocal microscopy is a useful tool for
      studying corneal cell populations. Central corneal cell densities were found to
      decrease significantly with age only in the endothelium. For the first time in
      human corneas using in vivo confocal microscopy, this study statistically
      confirms a higher apparent number of keratocytes in the anterior stroma than in
      the posterior stroma.

PMID- 9756443
TI  - In vivo confocal microscopy of Fuchs' endothelial dystrophy.
AB  - PURPOSE: The purpose of this study is to analyze in vivo confocal microscopic
      findings of corneas with Fuchs' endothelial dystrophy. METHODS: Central corneas
      of 17 eyes of 11 patients aged 41-86 years were examined using in vivo scanning
      slit confocal microscopy after being diagnosed with Fuchs' endothelial dystrophy.
      The cellular structure of the corneas was analyzed morphologically and
      quantitatively and compared to control results from 22 healthy corneas. RESULTS:
      Bullae were detected in the basal epithelial layer of one eye. Eight of 17 eyes
      (47%) exhibited an abnormal Bowman's layer: diffuse bright reflection and absence
      of nerves. Eleven eyes (65%) exhibited abnormal anterior stroma: lacunae and
      diffuse increased light reflection due to edema. In 12 eyes (71%), lacunae or
      dark bands 5-20 microm wide against increased background reflection were noted in
      the posterior stroma. Descemet's membrane was thickened in all eyes. Dark bands
      were detected in six eyes (35%). Guttae (137-1,231/mm2) 20-40 microm in diameter
      were found in every endothelial cell layer. The mean endothelial cell count was
      1,202 +/- 850 (cells/mm2 +/- SD; range, 0-2,735). There was a positive
      correlation between endothelial cell counts obtained by specular microscopy and
      those obtained by confocal microscopy (r = 0.95). CONCLUSION: In vivo confocal
      microscopic findings of Fuchs' endothelial dystrophy are described for the first
      time in a series of cases. Pathological changes in Fuchs' dystrophy were detected
      in all corneal layers, more frequently in the posterior layers. Endothelial cell
      counts obtained with confocal microscopy were statistically similar to those
      obtained with standard specular microscopy.

PMID- 9756444
TI  - The association between ocular cicatricial pemphigoid and rheumatoid arthritis.
AB  - PURPOSE: To assess the pathogenesis, symptomatology, and severity of rheumatoid
      arthritis (RA) in patient's with concomitant ocular cicatricial pemphigoid (OCP).
      METHODS: We retrospectively analyzed the charts of eight patients seen at a
      single institution between the years 1972 and 1997 with concomitant RA and OCP.
      Patients with OCP secondary to medical therapy, radiation, or chemical burns, or
      Stevens-Johnson syndrome were excluded. RESULTS: The female-to-male ratio was
      7:1. All patients had positive serum rheumatoid factors and immunohistochemical
      confirmation of OCP. The mean number of years of RA prior to OCP diagnosis was
      19. The number of patients with stage II OCP was three of eight (37.5%). The
      number of patients with stage III OCP was five of eight (62.5%). All patients had
      radiologic evidence of degenerative joint disease and synovial thickening. All
      eight patients had keratoconjunctivitis sicca, five of eight patients (62.5%) had
      Sjogren's syndrome, and five of eight patients (62.5%) developed rheumatoid
      cornea necrosis leading to corneal perforation. CONCLUSIONS: The implication
      exists that RA and OCP may be linked via an immunologically mediated mechanism
      and that patients with severe extraarticular symptoms associated with RA may be
      more likely to develop OCP. Prompt recognition of overlying symptoms may
      facilitate proper therapy for control of both diseases.

PMID- 9756445
TI  - Photorefractive keratectomy using the summit SVS Apex laser with or without
      astigmatic keratotomy.
AB  - PURPOSE: The purpose of this study was to evaluate the results of myopic
      photorefractive keratectomy (PRK) with or without astigmatic keratotomy (AK) for
      different levels of intended correction by using the SVS Apex laser. METHODS:
      This is a retrospective cohort study of 226 eyes that had PRK for myopia ranging
      from -1.0 to -7.6 diopters and 6 months of follow-up. In addition, 64 of these
      eyes had AK for naturally occurring or laser-induced astigmatism. Uncorrected
      visual acuity, spectacle-corrected visual acuity, and corneal topography with
      quantitative descriptors of surface regularity (SRI) and surface asymmetry (SAI)
      were used to monitor the results of PRK with or without AK. RESULTS: At 6 months,
      95.6% eyes had an uncorrected visual acuity of 20/40 or better, 90% eyes were
      within +/-1.0 diopter of emmetropia, and 3.1% eyes lost two lines of best
      corrected vision. No eyes lost more than two lines of best-corrected vision. Mean
      refractive astigmatism was reduced, but mean SAI and SRI were increased, 6 months
      after PRK. Uncorrected vision, best-corrected vision, and predictability
      decreased, whereas SAI and SRI increased, with increasing attempted correction.
      CONCLUSION: PRK, with or without AK, effectively reduced myopia in all eyes by 6
      months after surgery. Predictability tended to decrease with increasing attempted
      correction, even for eyes with relatively low to moderate myopia. PRK may induce
      surface asymmetry and irregularity at 6 months, and these alterations tend to be
      greater as the attempted correction increases.

PMID- 9756446
TI  - Corneal astigmatism after scleral buckling surgery assessed by Fourier analysis
      of videokeratography data.
AB  - PURPOSE: To evaluate quantitatively the changes in corneal curvature, including
      irregular astigmatism, after scleral buckling surgery for retinal detachment.
      METHODS: In 29 eyes of 29 patients undergoing scleral explant surgery,
      videokeratographic measurements were carried out before and 1 week, 1 month, and
      3 months after surgery. Using Fourier harmonic analysis, dioptric data on mire
      rings were decomposed into spherical, regular astigmatic, and irregular
      astigmatic (decentration and higher order irregularity) components. RESULTS: The
      irregular astigmatic component significantly increased at 1 week postoperatively
      but returned to the preoperative level 1 month after surgery. The regular
      astigmatism also displayed a transient increase up to 1 month after surgery. The
      increases in regular astigmatism were significant in eyes that had scleral
      buckling of < or =180 degrees but not in eyes with buckles extending >180
      degrees. CONCLUSION: Changes in irregular astigmatism after retinal detachment
      surgery were quantitatively evaluated. The scleral buckling surgery causes a
      transient increase in irregular astigmatism as well as regular astigmatism.

PMID- 9756447
TI  - Comparison of three computerized videokeratoscopy systems with keratometry.
AB  - PURPOSE: To compare the reproducibility of computerized videokeratoscopy systems
      by using normal eyes and calibrated objects. METHODS: We evaluated the
      reproducibility of three commercially available videokeratoscopes [EyeSys,
      TechnoMed C-Scan, and PAR Corneal Topography System (CTS)] with the manual
      keratometer (Bausch & Lomb) by using calibration spheres and 10 normal subjects
      (20 eyes). All videokeratoscopy and keratometer results were obtained by one
      investigator (R.M.). Each eye and calibration sphere were submitted to 10 serial
      examinations by using each system. The average K of all points within the central
      3.0 mm of the topography systems (central 3.0 mm) was compared with the average K
      of the manual keratometer. RESULTS: All videokeratoscopy systems correlated well
      with each other and manual keratometry when accessing aspheric and spherocylinder
      calibration balls. EyeSys central keratometry clinical results had the strongest
      correlation with the average keratometry results at 35%, followed by PAR-CTS at
      25% and C-Scan at 5%. Among the videokeratoscopy units, EyeSys and PAR-CTS had
      the strongest correlation at 65%. The correlation between the TechnoMed C-Scan
      and both the EyeSys and PAR-CTS systems was 25%. There was a statistically
      significant difference (p < 0.05) between the systems when analyzing the results
      obtained from clinical subjects. The average keratometry (K) difference of human
      eyes between videokeratoscopy systems is <0.35 diopters (D) (p < 0.05), which may
      be clinically significant. The average manual K reading (42.97 D) is
      statistically significantly flatter (p < 0.05) than each of the videokeratoscopy
      units (EyeSys = 43.49 D; PAR = 43.48 D; C-Scan = 43.83 D). Comparing the 10
      measurements of each eye or calibration object in the same videokeratoscopy
      system verified that the devices give reproducible results. The average standard
      deviation (ASD) of the keratometer was 0.10 D. The ASD of the videokeratoscopy
      units was 0.05 D for the EyeSys, 0.29 D for the PAR-CTS, and 0.31 D for the C
      Scan systems. CONCLUSION: Based on this study, we should not assume that the
      results of different topography systems can be interchanged in clinical studies.

PMID- 9756448
TI  - Effect of norepinephrine on proliferation, migration, and adhesion of SV-40
      transformed human corneal epithelial cells.
AB  - PURPOSE: To determine the ability of norepinephrine to modulate proliferation,
      adhesion, and migration of SV-40 transformed human corneal epithelial cells.
      METHODS: Assays were performed using SV-40 transformed human corneal epithelial
      cells. For proliferation assays, cells were plated in 96-well plates coated with
      fibronectin and collagen (FNC). A dose-response curve was generated for
      norepinephrine in concentrations of 100 nM-100 microM. The cell number in each
      well was evaluated using the fluorochrome Calcein AM (an intracellular esterase
      cleavage substrate), and fluorescence was determined using an automated
      fluorescent plate reader. For cell adhesion, 25 x 10(-3) cells were plated onto
      FNC-coated 96-well plates, incubated in 10 nM-100 microM norepinephrine for 90
      min, gently irrigated, and the remaining adherent cells quantitated. Cell
      migration was measured using blind-well migration chambers with a 10-microm pore
      size and FNC-coated filters. Cells (250 x 10(3)) were added to the upper chamber,
      incubated for 18 h in the presence of factors, after which time the cells that
      had migrated through the filter were quantitated. The toxicity of norepinephrine
      was evaluated using a standard Live/Dead assay employing the combined
      fluorochromes of ethidium homodimer (to indicate dead cells) and Calcein AM (to
      indicate viable cells). Varying concentrations of norepinephrine were added, and
      the cells incubated for 3 h and the fluorometric assay performed. RESULTS:
      Norepinephrine stimulated corneal epithelial cell proliferation and migration
      over a wide range of concentrations. It did not modulate cell adhesion and
      demonstrated cell toxicity only at the highest (supraphysiologic) concentration
      tested. CONCLUSIONS: Norepinephrine is normally found in the cornea and may be
      important in the maintenance of normal corneal homeostasis and in wound-healing
      processes.

PMID- 9756449
TI  - Interlacing and cross-angle distribution of collagen lamellae in the human
      cornea.
AB  - PURPOSE: The interlacing and cross angles between the collagen lamellae within
      the human corneal stroma were studied by means of scanning electron microscopy
      (SEM). METHODS: For SEM, cells and noncollagenous extracellular matrix were
      removed with 10% sodium hydroxide. Transmission electron microscopy (TEM)
      preparations were performed according to standard procedures. The interlacing of
      lamellae was studied within the limbal, paracentral, and central regions of five
      different layers. The cross angles between the longitudinal axes of adjacent
      lamellae were measured. The distribution of these angles within defined layers
      and regions was compared. Special attention was paid to the interlacing of the
      lamellae. RESULTS: Lamellae split in an anteroposterior direction as well as
      horizontally into branches and are interlaced by crossing the fissures between
      the branches. Smaller lamellae cross through clefts of neighboring lamellae. The
      cross angles show a high variability of 1 degree - 90 degrees. With the exception
      of the limbal region of the layer adjacent to Descemet's membrane, the
      distribution of cross angles is similar. A frequent occurrence of cross angles
      <30 degrees (68%) in this limbal layer can be explained by a pseudocircular
      orientation (ligamentum circulare corneae) of the lamellae. CONCLUSION: The
      present study shows that the three-dimensional organization of the collagen
      lamellae is characterized by a greater extent of lamellar interlacing than has
      been assumed until now.

PMID- 9756450
TI  - Characterization of specular "dark events" in human donor corneal endothelium by
      scanning and transmission electron microscopy.
AB  - PURPOSE: To evaluate changes in the donor corneal endothelium in the intact globe
      and in the in vivo rabbit cornea to characterize more fully the formation of
      "dark events" without relief images in the endothelial mosaic. METHODS: Six ex
      vivo human donor corneas in the intact globe and an in vivo rabbit model were
      used to assess the morphological changes associated with osmotically increasing
      fluid movement from the anterior chamber into the stroma by specular (SM),
      confocal (CM), and transmission and scanning electron microscopy (TEM, SEM).
      RESULTS: After application of hyperosmotic solution on the anterior surface of
      the cornea, dark events without relief images were observed by SM and CM. In both
      human and rabbit corneas, SEM showed that apical pores at the Y-junctions between
      endothelial cells became enlarged. Large subendothelial spaces were observed on
      Descemet's membrane by TEM with some spaces communicating with the anterior
      chamber. CONCLUSIONS: The findings suggest that these openings at the Y-junctions
      may represent intercellular channels that may also act as pathways for the
      formation of intercellular and subendothelial vacuoles in both the rabbit and
      human donor corneal endothelium. By virtue of their location, these vacuoles are
      characterized by lack of relief images as seen with the contact SM.

PMID- 9756451
TI  - Efficacy of cobalt chelates in the rabbit eye model for epithelial herpetic
      keratitis.
AB  - PURPOSE: A new class of antiviral agent, cobalt chelates (the CTC series), was
      evaluated for treating epithelial herpetic keratitis, consequent stromal disease
      being the major infectious cause of blindness in industrial nations. METHODS:
      Effects of CTC complexes were monitored in cell cultures and in a rabbit eye
      model, either infected with herpes simplex virus type 1 (HSV-1) or uninfected.
      Several antiviral concentrations of CTC complexes nontoxic to Vero cells were
      administered to rabbit eyes with HSV-1-induced keratitis. Corneal surface virus
      titers were measured, and corneal lesions of epithelial keratitis were monitored
      by slit-lamp microscopy and scored. Recovery rates and incidence were compared in
      eyes treated with CTC complexes, placebo, or clinically formulated
      trifluorothymidine (Viroptic), using nonparametric statistics. RESULTS: All CTC
      complexes inhibited HSV-1 replication in vitro, CTC-96 being best. CTC-96, CTC
      23, and CTC-67 eliminated (<1 plaque-forming unit[pfu]) corneal surface HSV-1
      (otherwise >10(5) pfu) in order of descending potency, but CTC-82 was
      ineffective. CTC-96 (either 5 microg/ml six times daily or 10 microg/ml five
      times daily) accelerated herpetic dendritic keratitis recovery better than or the
      same as trifluorothymidine (10 mg/ml nine times daily). CTC complexes were
      nontoxic to Vero cells continuously exposed to < or =25 microg/ml; 50 microg/ml
      of CTC 96 nine times daily did not irritate uninfected rabbit eyes. CONCLUSION:
      Topical CTC-96 applications were at least as effective as Viroptic in diminishing
      disease signs and corneal surface virus at concentrations less than one
      thousandth that of Viroptic.

PMID- 9756453
TI  - Pterygium with granuloma faciale-like histologic picture.
AB  - PURPOSE: Description of a case with an atypical conjunctival pterygium with an
      unusual histologic picture suggesting granuloma faciale, a vasculitis-like
      disease of facial skin with a chronic, indolent course. Discussion of diagnosis
      and treatment. METHODS: Repeated clinical and histologic observations. RESULTS: A
      pterygium with an unusual nasosuperior localization was excised and examined
      microscopically. There was a dense vessel-related inflammatory infiltrate,
      essentially identical to granuloma faciale. The lesion recurred and, as granuloma
      faciale is amenable to dapsone (diphenyl sulfone), treatment with 100 mg daily
      resulted in rapid improvement, whereas reduction of the dose to 50 mg daily
      resulted in relapse. Reinstitution of the original dose resulted in normalization
      of the histologic picture. However, a recurrent pterygium developed, which had a
      quite unspecific histologic picture. CONCLUSION: A disease with a histologic
      picture essentially identical to granuloma faciale may manifest itself as a
      pterygium. Treatment with dapsone may be beneficial.

PMID- 9756452
TI  - Nosocomial Klebsiella pneumoniae conjunctivitis resulting in infectious keratitis
      and bilateral corneal perforation.
AB  - PURPOSE: Klebsiella pneumoniae is a known cause of metastatic endophthalmitis.
      However, the organism has never been described to cause severe infectious
      keratoconjunctivitis. We report a fulminant case of nosocomial K. pneumoniae
      conjunctivitis complicated by infectious keratitis and corneal perforation in
      both eyes. METHODS: An 83-year-old previously healthy Chinese woman, blind in the
      right eye from rubeotic glaucoma and with bilateral dense cataracts, was admitted
      for observation after a head injury. While in hospital, she developed purulent
      bilateral conjunctivitis. Repeated cultures grew K. pneumoniae. This rapidly
      progressed to severe infectious keratitis and corneal perforation in both eyes,
      despite intensive antibiotics to which the organism was susceptible. The patient
      was otherwise well, and investigations did not reveal any source of endogenous
      sepsis. RESULTS: The patient lost complete vision in both eyes. The left eye
      turned phthisical, and the right eye was eviscerated for uncontrolled
      endophthalmitis. CONCLUSION: Although not previously reported, K. pneumoniae can
      cause devastating keratoconjunctivitis resulting in corneal melt, perforation,
      and uncontrolled endophthalmitis.

PMID- 9756454
TI  - Recurrent Meesmann's corneal epithelial dystrophy after penetrating keratoplasty.
AB  - PURPOSE: To characterize the histopathology of recurrent Meesmann's corneal
      epithelial dystrophy after penetrating keratoplasty. METHODS: Postmortem
      examination by light and electron microscopy of the eyes of an 84-year-old
      patient with Meesmann's dystrophy who underwent a penetrating keratoplasty in the
      right eye at age 74 years and a lamellar keratoplasty in the left eye at age 51
      years. RESULTS: In the right eye, the characteristic features of Meesmann's
      dystrophy were demonstrated in both the donor and recipient corneas. The
      pathologic findings were limited to the corneal epithelium and included increased
      thickness, architectural disorganization, loss of cell polarity, increased
      amounts of intracellular glycogen, presence of intraepithelial microcysts
      containing degenerated cells, and in some cells, the presence of an electron
      dense fibrillogranular material associated with disrupted cytoplasmic filaments.
      In the left eye, the corneal findings were consistent with but not specific for
      Meesmann's dystrophy. These included architectural disorganization, loss of cell
      polarity, presence of intraepithelial microcysts, and irregular thickening of the
      basement membrane in the donor cornea. CONCLUSION: Meesmann's corneal epithelial
      dystrophy is demonstrated to recur after penetrating keratoplasty. This finding
      suggests that the abnormalities that lead to the disease are localized to the
      corneal epithelial cells and not in the stroma, as previously proposed.

PMID- 9756455
TI  - Multicenter drug study assessing in vitro antibiotic susceptibilities of ocular
      isolates.

PMID- 9756456
TI  - Trends in sexual risk behaviors among high school students--United States, 1991
      1997.
AB  - Each year, approximately three million cases of sexually transmitted diseases
      (STDs) occur among teenagers, and approximately one million become pregnant.
      Human immunodeficiency virus (HIV) infection is the sixth leading cause of death
      among persons aged 15-24 years in the United States. Unprotected sexual
      intercourse and multiple sex partners place young persons at risk for HIV
      infection, other STDs, and pregnancy. To determine trends in sexual risk
      behaviors among high school students, CDC analyzed data from the Youth Risk
      Behavior Survey (YRBS) for the years 1991, 1993, 1995, and 1997. This report
      summarizes the results of this analysis, which indicate that, from 1991 to 1997,
      the percentage of U.S. high school students who had ever had sexual intercourse
      decreased, and the prevalence of condom use among currently sexually active
      students increased.

PMID- 9756457
TI  - Epidemic typhoid fever--Dushanbe, Tajikistan, 1997.
AB  - Typhoid fever, a severe systemic illness transmitted through food or water, is
      caused by the bacterium Salmonella serotype Typhi. This report describes a major
      epidemic of typhoid fever in Dushanbe, Tajikistan, that resulted from
      contamination of the municipal water system. In Tajikistan, the Sanitary
      Epidemiologic Service (SES) maintains records for reportable diseases. Dushanbe
      (1997 population: 600,000) residents receive health care through assigned
      polyclinics; surveillance for reportable diseases is based on polyclinic records.
      A case of typhoid fever is defined as physician diagnosis or isolation of S.
      Typhi from stool, blood, or urine cultures. In February 1997, a sudden increase
      in the number of typhoid fever cases was identified by SES in Dushanbe, with
      approximately 2000 cases registered during a 2-week period. In March, the
      Ministry of Health of Tajikistan requested assistance from CDC. In collaboration
      with local authorities and nongovernmental partners, CDC reviewed epidemiologic
      and laboratory surveillance; conducted a case-control study to identify risk
      factors for infection; and evaluated municipal drinking water quality, water
      wastage, and health-education campaigns.

PMID- 9756458
TI  - Influenza A--Florida and Tennessee, July-August 1998, and virologic surveillance
      of influenza, May-August 1998.
AB  - During July and August 1998, the state departments of health in Florida and
      Tennessee each reported an outbreak of influenza. The Florida outbreak occurred
      in July in two residential homes for children; the Tennessee outbreak occurred in
      August among members of a family that vacationed together. This report summarizes
      the investigation of these outbreaks, which were caused by influenza type A(H3N2)
      viruses, and presents information on influenza isolates received by CDC during
      May-August 1998, 81% of which were influenza A(H3N2).

PMID- 9756459
TI  - Acquired multidrug-resistant tuberculosis--Buenaventura, Colombia, 1998.
AB  - In 1996, the incidence of tuberculosis (TB) in Colombia was 26.5 per 100,000
      population, and mortality was 3.4 per 100,000; in comparison, the incidence in
      Buenaventura, a port town on the Pacific coast, was 90.5 per 100,000, and
      mortality was 9.4 per 100,000. The prevalence of multidrug-resistant tuberculosis
      (MDR-TB) (i.e., Mycobacterium tuberculosis isolates resistant to at least
      isoniazid [INH] and rifampin [RIF]) was not known because susceptibility testing
      is not performed routinely, and data on drug resistance for the country have not
      been collected systematically. During October-November 1997, at the request of
      the Secretary of Health in Cali, Colombia, the International Center for Training
      and Medical Investigation in Cali performed sputum cultures for M. tuberculosis
      and drug-susceptibility testing on isolates from 18 (75%) of 24 TB patients in
      Buenaventura who were known to be clinically unresponsive to standard TB
      treatment. MDR-TB was identified in 12 (67%) of these patients, four of whom
      subsequently died. In March 1998, the International Center for Training and
      Medical Investigation and the Secretary of Health of Colombia invited CDC to
      participate in an investigation of these patients with MDR-TB. This report
      summarizes the findings of this investigation, which indicated that
      inconsistencies in treatment may have contributed to this outbreak, and provides
      recommendations for the prevention and control of MDR-TB in Buenaventura.

PMID- 9756460
TI  - Report on survey regarding collection and use of cause of injury data by states.
AB  - In October 1997, the Injury Control and Emergency Health Services Section of the
      American Public Health Association (APHA) conducted a survey of all 50 states,
      the District of Columbia (DC), and Puerto Rico to assess the availability of
      external cause-of-injury data in statewide hospital discharge data systems
      (HDDS), hospital emergency department data systems (HEDDS), and other ambulatory
      care data systems. The report on the findings of the analysis, How States are
      Collecting and Using Cause of Injury Data, includes recommendations for improving
      the quality and availability of statewide injury-related data for injury
      prevention activities.

PMID- 9756461
TI  - Development of Bacillus thuringiensis fermentation and process control from a
      practical perspective.
AB  - Bacillus thuringiensis (Bt) is the most widely used biopesticide producer in the
      biological control market. It is very critical for the Bt pesticide industry to
      be able to achieve a high yield in the Bt fermentation process in order to reduce
      its cost and compete with chemical pesticides in the market. We review the
      overall development of Bt fermentation process research and provide our point of
      view for the future research opportunities and potential improvements. This
      minireview covers the areas of fermentation physiology, growth dynamics and high
      yield process control. It is pointed out that many studies aimed to improve spore
      count and process research focusing on toxin protein yield is lacking. In
      addition, significant development opportunities reside in the process development
      for the genetically engineered Bt strains expressing multiple toxin proteins.

PMID- 9756462
TI  - Degradation of human cardiac troponin I after myocardial infarction.
AB  - Cardiac troponin I (TnI) is the inhibitory subunit of the troponin complex and a
      specific biochemical marker for myocardial infarction (MI). It is released into
      the bloodstream within 4-6 h following MI, peaks after 18-24 h and remains
      elevated for up to 7 days. In this work, I have identified TnI forms present in
      MI-patient serum. By immobilizing anti-TnI antibodies, which recognize various
      epitopic sites on the TnI molecule, we were able to isolate TnI from MI-patient
      serum pools. Western-blot analysis following SDS/PAGE shows two major TnI
      fragments with apparent molecular masses of 18000 and 14000 Da. Either or both
      fragments are seen in serum obtained from individuals with MI. The fragments are
      generated as a result of proteolytic processing from the C-terminal region of
      TnI. Partial processing from the N-terminal of TnI is also seen and is associated
      with the generation of the 14000 Da fragment. Very little unprocessed intact TnI
      is detected in patient serum after MI. The degradation in vitro of cardiac TnI
      was studied by incubating either bovine or human recombinant TnI in serum.
      Western-blot analyses with TnI antibody showed that purified TnI spiked into
      normal human serum or MI-patient serum depleted of TnI degrades rapidly to lower
      molecular mass fragments. Degradation of TnI is associated with a loss in
      immunological activity. Serum TnI isolated by anti-TnI antibody, under non
      dissociating conditions, is associated with at least troponin C (TnC) and
      troponin T (TnT). This complex is bound by anti-TnI, anti-TnC and anti-TnT
      antibodies.

PMID- 9756463
TI  - An acidic glutaryl-7-aminocephalosporanic acid acylase from Pseudomonas
      nitroreducens.
AB  - A glutaryl-7-aminocephalosporanic acid (GL-7-ACA) acylase was purified 58-fold
      from Pseudomonas nitroreducens in a two-step procedure involving osmotic shock
      and carboxymethyl-Sepharose chromatography with a yield of 26%. The molecular
      mass of the native enzyme was 58 kDa. SDS/PAGE revealed that it consisted of two
      non-identical subunits with molecular masses of 35 and 21 kDa. The isoelectric
      point of the purified enzyme was 5.3. The enzyme had an optimal pH of 5.5 and an
      optimal temperature of 43 degrees C. The purified enzyme exhibited not only GL-7
      ACA acylase activity but also gamma-glutamyltranspeptidase activity. The Km
      values of the enzyme for GL-7-ACA and L-gamma-glutamyl p-nitroanilide were 10.41
      mM and 5.92 microM respectively.

PMID- 9756464
TI  - Surface-induced changes in the structure and activity of enzymes physically
      immobilized at solid/liquid interfaces.
AB  - A proteolytic enzyme, alpha-chymotrypsin, and a lipolytic enzyme, cutinase, were
      adsorbed from aqueous solutions on solid surfaces with different hydrophobicities
      and morphologies. With both enzymes the affinity of adsorption is larger for the
      more hydrophobic surface. Water-soluble, flexible oligomers grafted on the
      sorbent surface cause a decrease in enzyme adsorption. CD spectroscopy and
      differential scanning calorimetry (DSC) indicate severe structural perturbations
      in the enzymes resulting from adsorption. The CD spectra reflect an average of
      the structure of the whole protein population. The DSC data allow additional
      conclusions to be drawn on the heterogeneity in the conformational states of the
      adsorbed enzymes. The degree of structural perturbation, that is the fraction of
      the adsorbed molecules of which the structure is perturbed, is lower at a surface
      that (1) is less hydrophobic, (2) contains water-soluble flexible oligomers and
      (3) is more covered by the protein. The specific activities of the enzymes are
      decreased on adsorption, more or less following the extent of structural
      perturbation. Unlike in solution, in the adsorbed state the heat-induced
      inactivation process is not identical with the heat-induced unfolding process.
      Furthermore, when the enzymes are adsorbed their specific activities are much
      less sensitive to temperature variation.

PMID- 9756465
TI  - Immobilization of alpha-amylase on poly(vinyl alcohol)-coated perfluoropolymer
      supports for use in enzyme reactors.
AB  - The suitability and potential for the use of poly(vinyl alcohol) (PVA)-coated
      solid perfluoropolymers in immobilized-enzyme engineering have been evaluated by
      using alpha-amylase from Bacillus licheniformis for the hydrolysis of starch.
      alpha-Amylase was covalently immobilized on PVA-coated poly(tetrafluoroethylene
      hexafluoropropylene) (PVA-FEP) by covalent coupling with the use of p-beta
      sulphate-(ethyl sulphonide)-aniline, 2,4,6-trichloro-1,3,5-triazine, 1.1'
      carbonyldi-imidazole and 2,2, 2-trifluoroethanesulphonyl chloride activation
      procedures, and also for comparison with cyanogen bromide-activated Sepharose 4B.
      In all cases, immobilization greatly improved the thermostability of the alpha
      amylase and its resistance to inactivation by 6 M urea. Also the enhancements of
      enzymic activities with increased temperature were higher for the immobilized
      enzymes than for the soluble enzyme, and the immobilized alpha-amylases were well
      suited to the continuous hydrolysis of starch conducted at elevated temperatures.
      Although the specific activities of the enzymes immobilized on PVA-FEP were lower
      than for that immobilized to Sepharose 4B, these novel supports showed far
      superior strength. The enzymes immobilized on PVA-FEP were able to be readily
      recovered from stirred batch bioreactors for repeated reuse, whereas the enzymes
      immobilized to Sepharose were fractured and fragmented under similar conditions
      of stirring. A conventional fixed-bed bioreactor was found to be unsuitable for
      continuous starch hydrolysis owing to an unacceptable build-up of pressure drop
      across the bed. However, an expanded bed reactor containing alpha-amylase
      immobilized on solid PVA-coated perfluorocarbon showed great potential for the
      continuous hydrolysis of starch. Only 20% of the enzyme activity was lost after
      use for 3 weeks at 72 degrees C. It is concluded that PVA-coated solid
      perfluorocarbon is a highly promising support for use in immobilized enzyme
      engineering.

PMID- 9756466
TI  - Amplification of flow-microcalorimetry signal by means of multiple bioaffinity
      layering of lectin and glycoenzyme.
AB  - This paper demonstrates a positive influence of a special, stepwise technique of
      enzyme immobilization based on the biospecific adsorption of the glycoenzyme
      invertase on immobilized concanavalin A (Con A), subsequent adsorption of the
      free Con A on the immobilized invertase:Con A support and repeated adsorption of
      invertase on the support. A 3-fold repetition of the same procedure designed
      preliminarily as bioaffinity layering afforded up to a 10-fold increase in
      catalytic activity of the immobilized invertase. Reactive hydrogels based on bead
      cellulose and bead poly(glycidyl methacrylate) were used as immobilization
      supports for the preparation of these highly active preparations. The enhancement
      in catalytic activity of immobilized invertase preparations was demonstrated
      thermometrically, by flow microcalorimetry. Further attractive aspects for
      utilizing the signal amplification of biosensors with immobilized enzymes are
      discussed.

PMID- 9756467
TI  - Expression of recombinant Lym-1 single-chain Fv in Escherichia coli.
AB  - Lym-1 single-chain Fv (sFv) can be used for targeted radiodiagnosis and therapy
      of B-lymphocytic malignancies. Lym-1 sFv was constructed and expressed as a
      glutathione S-transferase fusion protein, using a (G4S)3 linker connecting the C
      terminus of the VH domain and the N-terminus of the VL domain of Lym-1. Six
      histidine residues and an E Tag epitope were introduced at the C-terminus of the
      sFv. Lym-1 sFv was purified with glutathione-Sepharose 4B affinity chromatography
      followed by digestion with thrombin. Lym-1 sFv of 28 kDa was confirmed by Western
      blotting with anti-(E Tag) monoclonal antibody. An antigen binding assay of Lym-1
      and a CD study indicated that it is functionally active.

PMID- 9756468
TI  - Chromatographic removal and heat inactivation of hepatitis B virus during the
      manufacture of human albumin.
AB  - The purpose of the present study was to examine the efficacy of the
      chromatographic and pasteurization steps, employed in the manufacture of human
      albumin, in the removal and/or inactivation of hepatitis B virus (HBV). Most
      human albumins manufactured today are prepared from donor plasma by fractionation
      methods that use precipitation with cold ethanol. CSL Limited, an Australian
      biopharmaceutical company, has recently converted its method of manufacture for
      albumin from a traditional Cohn fractionation method to a method employing
      chromatographic techniques. A step-by-step validation of virus removal and
      inactivation was performed on this manufacturing process, which includes a DEAE
      Sepharose(R) and CM-Sepharose(R) Fast Flow ion-exchange step, a Sephacryl(R) S200
      High-Resolution gel-filtration step and a bulk pasteurization step where product
      is held at 60 degreesC for 10 h. HBV partitioning experiments were conducted on
      scaled-down chromatographic columns with hepatitis B surface antigen (HBsAg) as a
      marker, whereas the HBV model virus, duck HBV, was used to study the inactivation
      kinetics during pasteurization. Reductions for HBsAg through the three
      chromatographic steps resulted in a total log10 decrease of 1.5 log10, whereas
      more than 6.5 log10 decrease in duck HBV in Albumex(R)5 was achieved during
      pasteurization.

PMID- 9756469
TI  - alpha-Galactosidases of Penicillium simplicissimum: production, purification and
      characterization of the gene encoding AGLI.
AB  - Production of extracellular a-galactosidases by the filamentous fungus
      Penicillium simplicissimum (previously P. janthinellum) VTT-D-78090 was studied
      on different carbon sources. Steam-exploded oat husks were chosen as the best
      carbon source for enzyme production. Three a-galactosidases (AGL) were purified
      from the culture filtrate using ion-exchange chromatography, hydrophobic
      interaction chromatography and gel filtration. The isoelectric points of AGLI,
      AGLII and AGLIII were 5.2, 4.4 and 7.0, and the molecular masses as determined by
      SDS/PAGE were 61, 84 and 61 kDa, respectively. All enzymes were glycosylated. The
      optimum pH for the activity of AGLI and AGLIII was between 3.0 and 4.5 and that
      of AGLII was between 4.0 and 5.0. AGLII was more stable and more resistant to
      product inhibition by galactose than the other two enzymes. AGLI and AGLIII were
      also inhibited by p-nitrophenol-a-D-galactopyranoside, the substrate used for
      enzyme activity assay. The gene encoding AGLI was cloned and sequenced. The gene,
      agl1, encodes 435 amino acids including the signal sequence. It showed similarity
      with the other a-galactosidases belonging to the glycosyl hydrolase family 27.
      The N-terminal amino acid sequence of AGLIII was also similar to the sequences of
      other members of family 27, whereas the N-terminus of AGLII was completely
      different from the sequences of other reported hydrolases.

PMID- 9756470
TI  - An Arabidopsis mutant defective in the plastid general protein import apparatus.
AB  - Elaborate mechanisms have evolved for the translocation of nucleus-encoded
      proteins across the plastid envelope membrane. Although putative components of
      the import apparatus have been identified biochemically, their role in import
      remains to be proven in vivo. An Arabidopsis mutant lacking a new component of
      the import machinery [translocon at the outer envelope membrane of chloroplasts
      (Toc33), a 33-kilodalton protein] has been isolated. The functional similarity of
      Toc33 to another translocon component (Toc34) implies that multiple different
      translocon complexes are present in plastids. Processes that are mediated by
      Toc33 operate during the early stages of plastid and leaf development. The data
      demonstrate the in vivo role of a translocon component in plastid protein import.

PMID- 9756471
TI  - Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha
      therapy.
AB  - To better understand the dynamics of hepatitis C virus and the antiviral effect
      of interferon-alpha-2b (IFN), viral decline in 23 patients during therapy was
      analyzed with a mathematical model. The analysis indicates that the major initial
      effect of IFN is to block virion production or release, with blocking efficacies
      of 81, 95, and 96% for daily doses of 5, 10, and 15 million international units,
      respectively. The estimated virion half-life (t1/2) was, on average, 2.7 hours,
      with pretreatment production and clearance of 10(12) virions per day. The
      estimated infected cell death rate exhibited large interpatient variation
      (corresponding t1/2 = 1.7 to 70 days), was inversely correlated with baseline
      viral load, and was positively correlated with alanine aminotransferase levels.
      Fast death rates were predictive of virus being undetectable by polymerase chain
      reaction at 3 months. These findings show that infection with hepatitis C virus
      is highly dynamic and that early monitoring of viral load can help guide therapy.

PMID- 9756472
TI  - Mechanisms of directed attention in the human extrastriate cortex as revealed by
      functional MRI.
AB  - A typical scene contains many different objects, but the capacity of the visual
      system to process multiple stimuli at a given time is limited. Thus, attentional
      mechanisms are required to select relevant objects from among the many objects
      competing for visual processing. Evidence from functional magnetic resonance
      imaging (MRI) in humans showed that when multiple stimuli are present
      simultaneously in the visual field, their cortical representations within the
      object recognition pathway interact in a competitive, suppressive fashion.
      Directing attention to one of the stimuli counteracts the suppressive influence
      of nearby stimuli. This mechanism may serve to filter out irrelevant information
      in cluttered visual scenes.

PMID- 9756473
TI  - A structural basis for recognition of A.T and T.A base pairs in the minor groove
      of B-DNA.
AB  - Polyamide dimers containing three types of aromatic rings-pyrrole, imidazole, and
      hydroxypyrrole-afford a small-molecule recognition code that discriminates among
      all four Watson-Crick base pairs in the minor groove. The crystal structure of a
      specific polyamide dimer-DNA complex establishes the structural basis for
      distinguishing T.A from A.T base pairs. Specificity for the T.A base pair is
      achieved by means of distinct hydrogen bonds between pairs of substituted
      pyrroles on the ligand and the O2 of thymine and N3 of adenine. In addition,
      shape-selective recognition of an asymmetric cleft between the thymine-O2 and the
      adenine-C2 was observed. Although hitherto similarities among the base pairs in
      the minor groove have been emphasized, the structure illustrates differences that
      allow specific minor groove recognition.

PMID- 9756474
TI  - A carrot leucine-rich-repeat protein that inhibits ice recrystallization.
AB  - Many organisms adapted to live at subzero temperatures express antifreeze
      proteins that improve their tolerance to freezing. Although structurally diverse,
      all antifreeze proteins interact with ice surfaces, depress the freezing
      temperature of aqueous solutions, and inhibit ice crystal growth. A protein
      purified from carrot shares these functional features with antifreeze proteins of
      fish. Expression of the carrot complementary DNA in tobacco resulted in the
      accumulation of antifreeze activity in the apoplast of plants grown at greenhouse
      temperatures. The sequence of carrot antifreeze protein is similar to that of
      polygalacturonase inhibitor proteins and contains leucine-rich repeats.

PMID- 9756475
TI  - Role for the target enzyme in deactivation of photoreceptor G protein in vivo.
AB  - Heterotrimeric guanosine 5'-triphosphate (GTP)-binding proteins (G proteins) are
      deactivated by hydrolysis of the GTP that they bind when activated by
      transmembrane receptors. Transducin, the G protein that relays visual excitation
      from rhodopsin to the cyclic guanosine 3',5'-monophosphate phosphodiesterase
      (PDE) in retinal photoreceptors, must be deactivated for the light response to
      recover. A point mutation in the gamma subunit of PDE impaired transducin-PDE
      interactions and slowed the recovery rate of the flash response in transgenic
      mouse rods. These results indicate that the normal deactivation of transducin in
      vivo requires the G protein to interact with its target enzyme.

PMID- 9756476
TI  - An antimicrobial activity of cytolytic T cells mediated by granulysin.
AB  - Cytolytic T lymphocytes (CTLs) kill intracellular pathogens by a granule
      dependent mechanism. Granulysin, a protein found in granules of CTLs, reduced the
      viability of a broad spectrum of pathogenic bacteria, fungi, and parasites in
      vitro. Granulysin directly killed extracellular Mycobacterium tuberculosis,
      altering the membrane integrity of the bacillus, and, in combination with
      perforin, decreased the viability of intracellular M. tuberculosis. The ability
      of CTLs to kill intracellular M. tuberculosis was dependent on the presence of
      granulysin in cytotoxic granules, defining a mechanism by which T cells directly
      contribute to immunity against intracellular pathogens.

PMID- 9756477
TI  - Harnessing the biosynthetic code: combinations, permutations, and mutations.
AB  - Polyketides and non-ribosomal peptides are two large families of complex natural
      products that are built from simple carboxylic acid or amino acid monomers,
      respectively, and that have important medicinal or agrochemical properties.
      Despite the substantial differences between these two classes of natural
      products, each is synthesized biologically under the control of exceptionally
      large, multifunctional proteins termed polyketide synthases (PKSs) and non
      ribosomal peptide synthetases (NRPSs) that contain repeated, coordinated groups
      of active sites called modules, in which each module is responsible for catalysis
      of one complete cycle of polyketide or polypeptide chain elongation and
      associated functional group modifications. It has recently become possible to use
      molecular genetic methodology to alter the number, content, and order of such
      modules and, in so doing, to alter rationally the structure of the resultant
      products. This review considers the promise and challenges inherent in the
      combinatorial manipulation of PKS and NRPS structure in order to generate
      entirely "unnatural" products.

PMID- 9756479
TI  - Enhanced positive cloud-to-ground lightning in thunderstorms ingesting smoke from
      fires 
AB  - Smoke from forest fires in southern Mexico was advected into the U.S. southern
      plains from April to June 1998. Cloud-to-ground lightning (CG) flash data from
      the National Lightning Detection Network matched against satellite-mapped aerosol
      plumes imply that thunderstorms forming in smoke-contaminated air masses
      generated large amounts of lightning with positive polarity (+CGs). During 2
      months, nearly half a million flashes in the southern plains exhibited +CG
      percentages that were triple the climatological norm. The peak currents in these
      +CGs were double the expected value. These thunderstorms also produced abnormally
      high numbers of mesospheric optical sprites.

PMID- 9756478
TI  - Tomographic evidence for localized lithospheric shear along the altyn tagh fault 
AB  - Seismic tomography across the Altyn Tagh fault, at the north edge of the Tibetan
      Plateau, reveals a low P-wave velocity anomaly below the fault down to 140
      kilometers. This anomaly probably reflects strike-slip shear in the lithosphere.
      Slip-partitioning may also induce a wedge of crust from the Tarim Basin to plunge
      into the mantle.

PMID- 9756480
TI  - Triploblastic animals more than 1 billion years ago: trace fossil evidence from
      india 
AB  - Some intriguing bedding plane features that were observed in the Mesoproterozoic
      Chorhat Sandstone are biological and can be interpreted as the burrows of
      wormlike undermat miners (that is, infaunal animals that excavated tunnels
      underneath microbial mats). These burrows suggest that triploblastic animals
      existed more than a billion years ago. They also suggest that the diversification
      of animal designs proceeded very slowly before the appearance of organisms with
      hard skeletons, which was probably the key event in the Cambrian evolutionary
      explosion, and before the ecological changes that accompanied that event.

PMID- 9756481
TI  - ROSAT X-ray detection of a young brown dwarf in the chamaeleon I dark cloud 
AB  - Photometry and spectroscopy of the object Cha Halpha 1, located in the Chamaeleon
      I star-forming cloud, show that it is a approximately 10(6)-year-old brown dwarf
      with spectral type M7.5 to M8 and 0.04 +/- 0.01 solar masses. Quiescent x-ray
      emission was detected in a 36-kilosecond observation with 31.4 +/- 7.7 x-ray
      photons, obtained with the Rontgen Satellite (ROSAT), with 9final sigma detection
      significance. This corresponds to an x-ray luminosity of 2.57 x 10(28) ergs per
      second and an x-ray to bolometric luminosity ratio of 10(-3.44). These are
      typical values for late M-type stars. Because the interior of brown dwarfs may be
      similar to that of convective late-type stars, which are well-known x-ray
      sources, x-ray emission from brown dwarfs may indicate magnetic activity.

PMID- 9756482
TI  - Measuring the spin polarization of a metal with a superconducting point contact 
AB  - A superconducting point contact is used to determine the spin polarization at the
      Fermi energy of several metals. Because the process of supercurrent conversion at
      a superconductor-metal interface (Andreev reflection) is limited by the minority
      spin population near the Fermi surface, the differential conductance of the point
      contact can reveal the spin polarization of the metal. This technique has been
      applied to a variety of metals where the spin polarization ranges from 35 to 90
      percent: Ni0.8Fe0.2, Ni, Co, Fe, NiMnSb, La0.7Sr0.3MnO3, and CrO2.

PMID- 9756483
TI  - Particle nucleation in the tropical boundary layer and its coupling to marine
      sulfur sources 
AB  - New particle formation in a tropical marine boundary layer setting was
      characterized during NASA's Pacific Exploratory Mission-Tropics A program. It
      represents the clearest demonstration to date of aerosol nucleation and growth
      being linked to the natural marine sulfur cycle. This conclusion was based on
      real-time observations of dimethylsulfide, sulfur dioxide, sulfuric acid (gas),
      hydroxide, ozone, temperature, relative humidity, aerosol size and number
      distribution, and total aerosol surface area. Classic binary nucleation theory
      predicts no nucleation under the observed marine boundary layer conditions.

PMID- 9756484
TI  - Synchronous climate changes in antarctica and the north atlantic 
AB  - Central Greenland ice cores provide evidence of abrupt changes in climate over
      the past 100,000 years. Many of these changes have also been identified in
      sedimentary and geochemical signatures in deep-sea sediment cores from the North
      Atlantic, confirming the link between millennial-scale climate variability and
      ocean thermohaline circulation. It is shown here that two of the most prominent
      North Atlantic events-the rapid warming that marks the end of the last glacial
      period and the Bolling/Allerod-Younger Dryas oscillation-are also recorded in an
      ice core from Taylor Dome, in the western Ross Sea sector of Antarctica. This
      result contrasts with evidence from ice cores in other regions of Antarctica,
      which show an asynchronous response between the Northern and Southern
      Hemispheres.

PMID- 9756485
TI  - Solution properties of single-walled carbon nanotubes 
AB  - Naked metallic and semiconducting single-walled carbon nanotubes (SWNTs) were
      dissolved in organic solutions by derivatization with thionychloride and
      octadecylamine. Both ionic (charge transfer) and covalent solution-phase
      chemistry with concomitant modulation of the SWNT band structure were
      demonstrated. Solution-phase near-infrared spectroscopy was used to study the
      effects of chemical modifications on the band gaps of the SWNTs. Reaction of
      soluble SWNTs with dichlorocarbene led to functionalization of the nanotube
      walls.

PMID- 9756486
TI  - Ammonia synthesis at atmospheric pressure 
AB  - Ammonia was synthesized from its elements at atmospheric pressure in a solid
      state proton (H+)-conducting cell-reactor. Hydrogen was flowing over the anode
      and was converted into protons that were transported through the solid
      electrolyte and reached the cathode (palladium) over which nitrogen was passing.
      At 570 degreesC and atmospheric pressure, greater than 78 percent of the
      electrochemically supplied hydrogen was converted into ammonia. The thermodynamic
      requirement for a high-pressure process is eliminated.

PMID- 9756487
TI  - II. Alcoholic liver injury involves activation of Kupffer cells by endotoxin.
AB  - It is well known that females show a greater susceptibility to alcohol-induced
      liver injury than males. Additionally, females who consume alcohol regularly and
      have been obese for 10 years or more are at greater risk for both hepatitis and
      cirrhosis. Female rats on an enteral alcohol protocol exhibit injury more quickly
      than males, with widespread fatty changes over a larger portion of the liver
      lobule. Levels of plasma endotoxin, intercellular adhesion molecule-1, free
      radical adducts, infiltrating neutrophils, and nuclear factor-kappaB are
      increased about twofold more in livers from female than male rats after enteral
      alcohol treatment. Estrogen treatment in vivo increases the sensitivity of
      Kupffer cells to endotoxin. Evidence has been presented that Kupffer cells are
      pivotal in the development of alcohol-induced liver injury. Destruction of
      Kupffer cells with gadolinium chloride (GdCl3) or reduction of bacterial
      endotoxin by sterilization of the gut with antibiotics blocks early inflammation
      due to alcohol. Similar results have been obtained with anti-tumor necrosis
      factor-alpha antibody. These findings led to the hypothesis that alcohol-induced
      liver injury involves increases in circulating endotoxin, leading to activation
      of Kupffer cells, which causes a hypoxia-reoxygenation injury. This idea has been
      tested using pimonidazole, a nitroimidazole marker, to quantitate hypoxia in
      downstream pericentral regions of the liver lobule. After chronic enteral
      alcohol, pimonidazole binding increases twofold. Enteral alcohol also increases
      free radicals detected with electron spin resonance. Importantly, hepatic hypoxia
      and radical production detected in bile are decreased by destruction of Kupffer
      cells with GdCl3. These data are consistent with the hypothesis that Kupffer
      cells participate in important gender differences in liver injury caused by
      alcohol.

PMID- 9756488
TI  - Efficient hepatic uptake and concentrative biliary excretion of a mercapturic
      acid.
AB  - The role of the liver in the disposition of circulating mercapturic acids was
      examined in anesthetized rats and in the isolated perfused rat liver using S-2,4
      dinitrophenyl-N-acetylcysteine (DNP-NAC) as the model compound. When DNP-NAC was
      infused into the jugular vein (150 or 600 nmol over 60 min) it was rapidly and
      nearly quantitatively excreted as DNP-NAC into bile (42-36% of the dose) and
      urine (48-62% of dose). Some minor metabolites were detected in bile (<4%), with
      the major metabolite coeluting on HPLC with the DNP conjugate of glutathione (DNP
      SG). Isolated rat livers perfused single pass with 3 microM DNP-NAC removed 72 +/
      9% of this mercapturic acid from perfusate. This rapid DNP-NAC uptake was
      unaffected by sodium omission, or by L-cysteine, L-glutamate, L-cystine, or N
      acetylated amino acids, but was decreased by inhibitors of hepatic sinusoidal
      organic anion transporters (oatp), indicating that DNP-NAC is a substrate for
      these transporters. The DNP-NAC removed from perfusate was promptly excreted into
      bile, eliciting a dose-dependent choleresis. DNP-NAC itself constituted
      approximately 75% of the total dose recovered in bile, reaching a concentration
      of 9 mM when livers were perfused in a recirculating mode with an initial DNP-NAC
      concentration of 250 microM. Other biliary metabolites included DNP-SG, DNP
      cysteinylglycine, and DNP-cysteine. DNP-SG was likely formed by a spontaneous
      retro-Michael reaction between glutathione and DNP-NAC. Subsequent degradation of
      DNP-SG by biliary gamma-glutamyltranspeptidase and dipeptidase activities
      accounts for the cysteinylglycine and cysteine conjugates, respectively. These
      findings indicate the presence of efficient hepatic mechanisms for sinusoidal
      uptake and biliary excretion of circulating mercapturic acids in rat liver and
      demonstrate that the liver plays a role in their whole body elimination.

PMID- 9756489
TI  - Indomethacin increases susceptibility to injury in human gastric cells
      independent of PG synthesis inhibition.
AB  - Indomethacin and other nonsteroidal anti-inflammatory drugs are commonly used to
      indirectly deduce the possible role of PGs in a process being studied. The
      objective of this study was to determine if indomethacin, at concentrations
      comparable to plasma and tissue levels obtained in humans taking therapeutic
      doses, predisposes human gastric cells to injury through inhibition of PGs or
      acts through an alternate mechanism. The role of intracellular Ca2+ in this
      damaging process was also assessed. Indomethacin pretreatment, although by itself
      nondamaging, was associated with elevated intracellular Ca2+ concentrations and
      an increased cellular permeability, an effect that was dependent on extracellular
      Ca2+. Furthermore, indomethacin pretreatment significantly predisposed AGS cells
      to injury induced by two dissimilar agents (deoxycholate and A-23187), both of
      which are associated with intracellular Ca2+ accumulation. The addition of
      exogenous PGs did not reverse the predisposition to injury induced by
      indomethacin. The observed effects of indomethacin were dependent on
      concentration and not on ability to inhibit PG synthesis. Similar effects were
      not observed with equipotent concentrations of ibuprofen or aspirin. Finally, the
      exacerbation of deoxycholate-induced injury induced by indomethacin was not
      observed when extracellular Ca2+ was removed. Indomethacin, by disturbing
      intracellular Ca2+ homeostasis, predisposes human gastric cells to injury through
      mechanisms independent of PG synthesis. The current study suggests that data
      resulting from studies employing only indomethacin as a PG synthesis inhibitor
      should be interpreted with caution.

PMID- 9756490
TI  - Protein kinase G expression in the small intestine and functional importance for
      smooth muscle relaxation.
AB  - In functional experiments, the nitric oxide (NO) donor N-morpholino-N-nitroso
      aminoacetonitrile or the cGMP analog 8-(4-chlorophenylthio)-cGMP caused a
      concentration-dependent, tetrodotoxin-resistant relaxation of precontracted
      strips from rat small intestine. The inhibitory effect of both substances was
      completely blocked at lower concentrations and was significantly attenuated at
      higher concentrations by the selective cGMP-dependent protein kinase (cGK)
      antagonist KT-5823 (1 microM). cGK-I was identified by immunohistochemistry in
      circular and longitudinal muscle, lamina muscularis mucosae, and smooth muscle
      cells of the villi and in fibroblast-like cells of the small intestine.
      Additionally, there was staining of a subpopulation of myenteric and submucous
      plexus neurons. Double staining for neuronal NO synthase (nNOS) and cGK-I
      demonstrated a colocalization of these two enzymes. Western blot analysis of
      smooth muscle preparations and isolated nerve terminals demonstrated that these
      structures predominantly contain the cGK-Ibeta isoenzyme, whereas the cGK-Ialpha
      expression is about threefold less. The isoform cGK-II was entirely confined to
      mucosal epithelial cells. These results show that cGK-I is expressed in different
      muscular structures of the small intestine and participates in the NO-induced
      relaxation of gastrointestinal smooth muscle. The presence of cGK-I in NOS
      positive enteric neurons further suggests a possible neuronal action site.

PMID- 9756491
TI  - Binding of [3H]palmitate to BSA.
AB  - Determination of the BSA-palmitate high-affinity binding constant (Ka)
      traditionally relied on the heptane-water partitioning technique. We used this
      technique to calculate Ka for the BSA-[3H]palmitate complex, to determine if Ka
      was independent of protein concentration, and to determine if the unbound
      [3H]palmitate concentration is constant at different BSA concentrations using
      constant BSA-to-palmitate molar ratios (range 1:1 to 1:4). After extensive
      extraction of non-[3H]palmitate radiolabeled substances, the heptane-to-buffer
      partition ratio, in the absence of BSA, was 702 +/- 19 (mean +/- SD, n = 6). This
      value was much lower than the predicted value of 1,376 and was highly dependent
      on which phase (organic or aqueous) initially contained the [3H]palmitic acid.
      The data were consistent with the notion of self-association of [3H]palmitate in
      the aqueous phase. Ka for the BSA-[3H]palmitate complex was determined to be
      similar (2.2 +/- 0.1) x 10(8) M-1 (mean +/- SD, P > 0.05) at all BSA
      concentrations studied. At each BSA-to-palmitate molar ratio, the equilibrium
      unbound ligand concentration was constant only at low BSA concentrations (<10
      microM) and at low BSA-to-palmitate molar ratios (i.e., 1:1 and 1:2). At higher
      BSA concentrations and molar ratios, the unbound ligand concentration increased
      with an increase in protein concentration. Hepatocyte uptake using the
      manufacturer-supplied radiolabeled product was significantly higher than with the
      purified product, suggesting that a non-[3H]palmitate radiolabel is also a
      substrate for the uptake process.

PMID- 9756492
TI  - Effect of feeding diets of varying fatty acid composition on apolipoprotein
      expression in newborn swine.
AB  - The purpose of this study was to determine the effect of chronic (1 wk) feeding
      of dietary triacylglycerol (TG) of varying fatty acid composition on small
      intestinal and hepatic apolipoprotein expression, as well as serum lipid and
      apolipoprotein concentrations, in newborn swine. Two-day-old female swine were
      fed one of three diets by gavage with the following lipid composition: medium
      chain TG (MCT; MCT oil), intermediate-chain saturated TG (ICST; coconut oil), and
      long-chain polyunsaturated TG (LCPUT; safflower oil) at 753 kJ . kg-1 . day-1
      with 51% of energy from fat. After 1 wk, serum lipids and apolipoprotein
      concentrations were measured, and jejunal apolipoprotein B (apo B) and apo A-I
      mass and apo B, apo A-I, apo A-IV, and apo C-III synthesis were measured. Liver
      was processed for determination of apo B and apo A-I mass and apo B, apo A-I, apo
      C-III, and beta-actin mRNA abundance by slot blot hybridization. Compared with
      the MCT and LCPUT groups, the ICST group had higher total serum cholesterol, TG,
      high-density lipoprotein (HDL)-cholesterol, and apo A-I concentrations. There
      were no differences among the three groups for intestinal apolipoprotein mass or
      synthesis. In liver, apo A-I mass was highest in the ICST group. Liver apo A-I
      and apo C-III mRNA abundance was highest in the ICST group. Among all three
      groups, hepatic apo A-I mass correlated significantly with plasma HDL-cholesterol
      concentrations, and serum TG concentrations correlated with hepatic apo C-III
      mRNA abundance. In conclusion, we found that in the newborn piglet, chronic
      feeding of ICST increases serum total cholesterol, TG, HDL-cholesterol, and apo A
      I concentrations and hepatic expression of apo A-I and apo C-III mRNA, compared
      with feeding of MCT or LCPUT. We speculate that increased hepatic apo A-I
      expression may contribute to the higher serum HDL and apo A-I concentrations in
      the ICST animals. Increased hepatic expression of apo C-III with ICST feeding may
      contribute to the higher serum TG concentrations by apo C-III-mediated inhibition
      of the catabolism of triacylglycerol-rich lipoproteins.

PMID- 9756493
TI  - Uptake and metabolism of structured triglyceride by Caco-2 cells: reversal of
      essential fatty acid deficiency.
AB  - Structured lipids have been proposed as efficient vehicles for the
      supplementation of essential fatty acids (EFA) to patients with malabsorption. We
      investigated how a novel structured triglyceride (STG), containing purely
      octanoic acid in the sn-1/sn-3 and [14C]linoleic acid in the sn-2 positions, was
      incorporated into different lipid classes in Caco-2 cells. We also evaluated the
      contribution of gastric lipase in the uptake and metabolism of [14C]linoleic acid
      from the STG. We furthermore determined the potential of the STG to correct EFA
      deficiency induced in Caco-2 cells. The absorption of STG by Caco-2 cells was
      significantly greater compared with that of triolein. The addition of human
      gastric lipase significantly enhanced cellular uptake of the labeled substrate,
      reflecting the stereoselectivity of gastric lipase to hydrolyze medium chain FA.
      Analysis of the intracellular lipids synthesized revealed a predominance of
      phospholipids-monoglycerides. Most of the radioactivity in the lipoproteins
      isolated from Caco-2 cells was recovered in TG-rich lipoproteins (45%) and to a
      lesser extent in the high-density lipoprotein (36%) and low-density lipoprotein
      (17%) fractions. The administration of STG to Caco-2 cells rendered EFA deficient
      produced a marked increase of the cellular level of linoleic and arachidonic
      acids. This resulted in a lower ratio of 20:3(n-9) to 20:4(n-6), reflecting the
      correction of EFA deficiency in Caco-2 cells. Our data demonstrate that STG, in
      the presence of gastric lipase, have beneficial effects on lipid incorporation,
      lipoprotein production, and EFA status, utilizing Caco-2 cells as a model of EFA
      deficiency.

PMID- 9756494
TI  - Immunolocalization of gastrin-dependent histidine decarboxylase activity in rat
      gastric mucosa during feeding.
AB  - The localization of histidine decarboxylase (HDC) activity in the
      enterochromaffin-like (ECL) cells of the oxyntic mucosa was studied during
      fasting and refeeding using monoclonal (CURE no. 44178) and polyclonal (CURE no.
      94211) antibodies directed against the COOH terminus of HDC (HDC-CT). Changes in
      HDC immunostaining were correlated with mucosal HDC enzyme activity.
      Immunoneutralization of circulating gastrin and atropine treatment during
      refeeding were used to determine the relative importance of gastrin and
      cholinergic mechanisms in the regulation of HDC activity and immunostaining.
      Fasting caused a rapid reduction in the number of ECL cells immunostaining for
      HDC that was correlated with an almost complete loss of mucosal HDC enzyme
      activity. Refeeding restored both HDC immunostaining and enzyme activity within 2
      4 h, and this response was inhibited by gastrin immunoneutralization but not by
      atropine treatment. Immunostaining was uniformly decreased and restored in the
      lower half of the oxyntic mucosa, which corresponds to the predominant area of
      ECL cells in the gastric gland. Histamine immunostaining and mucosal histamine
      content were not significantly changed during fasting and refeeding or by gastrin
      antibody and/or atropine treatment during refeeding. These findings indicate that
      HDC activity correlates with HDC-CT immunostaining and that both HDC activity and
      HDC-CT immunostaining are regulated by gastrin during refeeding.

PMID- 9756495
TI  - PYY stimulates synthesis and secretion of intestinal apolipoprotein AIV without
      affecting mRNA expression.
AB  - We tested whether exogenous peptide YY (PYY) can stimulate synthesis and
      lymphatic secretion of intestinal apolipoprotein AIV (apo AIV). Rats with
      mesenteric lymph fistulas and right atrial cannulas were given continuous
      intravenous infusions of control vehicle or PYY at 25, 50, 75, 100, or 200 pmol .
      kg-1 . h-1. PYY (75-200 pmol . kg-1 . h-1) stimulated lymphatic apo AIV output
      from 1.5- to 3.5-fold higher than basal output. In separate experiments, PYY (100
      pmol . kg-1 . h-1) produced a 60% increase in jejunal mucosal apo AIV synthesis
      but had no effect on mucosal apo AIV mRNA levels at doses up to 200 pmol . kg-1 .
      h-1. Finally, exogenous PYY infusion (100 pmol . kg-1 . h-1) produced a plasma
      PYY increment of 30 pM compared with an increment of 18.7 pM in response to ileal
      infusion of lipid. These results support the hypothesis that PYY may be an
      endocrine mediator of the effects of distal gut lipid on production and release
      of intestinal apo AIV, likely via a posttranscriptional mechanism of action.

PMID- 9756496
TI  - Histamine sensitivity of mesenteric afferent nerves in the rat jejunum.
AB  - The concept of functional interaction between mast cells and intestinal afferents
      is gaining support. We have therefore characterized the action of histamine on
      jejunal afferent discharge in the anesthetized rat. Whole nerve mesenteric
      afferent discharge was recorded in conjunction with intestinal pressure in
      response to a range of histamine agonists and antagonists. Histamine at 2, 4, and
      8 micromol/kg (iv) evoked a dose-dependent biphasic increase in afferent
      discharge together with a biphasic rise in intestinal pressure. However, these
      two events were mediated independently, since nifedipine (1 mg/kg) substantially
      reduced the intestinal pressure increase but not the afferent discharge. These
      responses were completely inhibited by pyrilamine (5 mg/kg) but unaffected by
      ranitidine (5 mg/kg) or thioperamide (2 mg/kg). Neither the selective H2 receptor
      agonist dimaprit nor the selective H3 receptor agonist R-alpha-methylhistamine
      caused any modulation of afferent discharge. We conclude that histamine
      stimulates an H1 receptor-mediated increase in mesenteric afferent discharge that
      is independent of intestinal motor events. This suggests that histamine
      potentially acts as a mediator in mast cell-to-afferent nerve communication in
      the small intestine.

PMID- 9756497
TI  - Persistence of Helicobacter pylori VacA toxin and vacuolating potential in
      cultured gastric epithelial cells.
AB  - The vacuolating toxin A (VacA) is one of the most important virulence factors in
      Helicobacter pylori-induced damage to human gastric epithelium. Using human
      gastric epithelial cells in culture and broth culture filtrate from a VacA
      producing H. pylori strain, we studied 1) the delivery of VacA to cells, 2) the
      localization and fate of internalized toxin, and 3) the persistence of toxin
      inside the cell. The investigative techniques used were neutral red dye uptake,
      ultrastructural immunocytochemistry, quantitative immunofluorescence, and
      immunoblotting. We found that VacA 1) is delivered to cells in both free and
      membrane-bound form (i.e., as vesicles formed by the bacterial outer membrane),
      2) localizes inside the endosomal-lysosomal compartment, in both free and
      membrane-bound form, 3) persists within the cell for at least 72 h, without loss
      of vacuolating power, which, however, becomes evident only when NH4Cl is added,
      and 4) generally does not degrade into fragments smaller than approximately 90
      kDa. Our findings suggest that, while accumulating inside the endosomal-lysosomal
      compartment, a large amount of VacA avoids the main lysosomal degradative
      processes and retains its apparent molecular integrity.

PMID- 9756498
TI  - Inhibition of Na+/H+ exchange stimulates CCK secretion in STC-1 cells.
AB  - It has been demonstrated that K+ channel regulation of membrane potential is
      critical for control of CCK secretion. Because certain K+ channels are pH
      sensitive, it was postulated that pH affects K+ channel activity in the CCK
      secreting cell line STC-1 and may participate in regulating CCK secretion. The
      present study examines the role of electroneutral Na+/H+ exchange on
      extracellular acidification and hormone secretion. Treatment of STC-1 cells with
      the amiloride analog ethylisopropyl amiloride (EIPA) to inhibit Na+/H+ exchange
      inhibited Na+-dependent H+ efflux and increased basal CCK secretion. Substituting
      choline for NaCl in the extracellular medium elevated basal intracellular Ca2+
      concentration and stimulated CCK release. Stimulatory effects on hormone
      secretion were blocked by the L-type Ca2+ channel blocker diltiazem, indicating
      that secretion was dependent on the influx of extracellular Ca2+. To determine
      whether the effects of EIPA and Na+ depletion were due to membrane
      depolarization, we tested graded KCl concentrations. The ability of EIPA to
      increase CCK secretion was inhibited by depolarization induced by 10-50 mM KCl in
      the bath. Maneuvers to lower intracellular pH (pHi), including reducing
      extracellular pH (pHo) to 7.0 or treatment with sodium butyrate, significantly
      increased CCK secretion. To examine whether pH directly affects membrane K+
      permeability, we measured outward currents carried by K+, using whole cell patch
      techniques. K+ current was significantly inhibited by lowering pHo to 7.0. These
      effects appear to be mediated through changes in pHi, because intracellular
      dialysis with acidic solutions nearly eliminated current activity. These results
      suggest that Na+/H+ exchange and membrane potential may be functionally linked,
      where inhibition of Na+/H+ exchange lowers pHi and depolarizes the membrane,
      perhaps through inhibition of pH-sensitive K+ channels. In turn, K+ channel
      closure and membrane depolarization open voltage-dependent Ca2+ channels, leading
      to an increase in cytosolic Ca2+ and CCK release. The effects of pHi on K+
      channels may serve as a potent stimulus for hormone secretion, linking cell
      metabolism and secretory functions.

PMID- 9756499
TI  - Effects of chronic ethanol consumption on cytokine regulation of liver
      regeneration.
AB  - Ethanol ingestion may interrupt the proregenerative signal transduction that is
      initiated by injury-related cytokines such as tumor necrosis factor (TNF)-alpha
      and TNF-alpha- inducible cytokines including interleukin (IL)-6. To test this
      theory, liver regeneration, TNF-alpha and IL-6 expression, and cytokine-regulated
      prereplicative events were compared in ethanol-fed rats and isocalorically fed
      controls after 70% partial hepatectomy (PH). Ethanol feeding inhibits hepatocyte
      replication and recovery of liver mass after PH but generally promotes induction
      of both cytokines in the liver and extrahepatic tissues (i.e., white adipose
      tissue). Cytokine-regulated events that occur early in the prereplicative period
      are influenced differentially. TNF-alpha-dependent increases in hepatic nuclear
      factor-kappaB (NF-kappaB) p50 and p65 expression and DNA binding activity are
      prevented, whereas IL-6-dependent inductions of hepatic Stat-3 phosphorylation
      and DNA binding activity occur normally. In contrast, events (e.g., induction of
      cyclin D1, cdk-1, cyclin D3, and p53 mRNA) that occur at the end of the
      prereplicative period are uniformly inhibited. These findings indicate that
      chronic ethanol ingestion arrests the regenerative process during the
      prereplicative period and demonstrate that increased TNF-alpha, IL-6 and Stat-3
      are not sufficient to assure hepatocyte proliferation after PH.

PMID- 9756500
TI  - Src kinase and PI 3-kinase as a transduction pathway in ceramide-induced
      contraction of colonic smooth muscle.
AB  - Ceramide mediates sustained contraction of smooth muscle cells. C2 ceramide
      induced a rapid increase in Src kinase activity within 15 s, peaked at 1 min, and
      was sustained up to 8 min. Contraction and Src kinase activity were inhibited in
      cells incubated in Ca2+-free medium containing 2 mM EGTA and in cells
      preincubated with herbimycin A, a Src kinase inhibitor. Immunoblotting using a
      phosphospecific anti-Src (416Y) antibody showed a ceramide-induced increase in
      pp60(src) tyrosine phosphorylation. Immunoprecipitation using an anti
      phosphotyrosine antibody followed by Western immunoblotting using a monoclonal
      IgG anti-phosphoinositide 3-kinase NH2 terminal-SH2 domain antibody showed a
      ceramide-induced increase in phosphoinositide 3-kinase (PI 3-kinase) tyrosine
      phosphorylation at a protein mass corresponding to 85 kDa, the regulatory subunit
      of PI 3-kinase, which contains the Src kinase binding site. PI 3-kinase
      phosphorylation was inhibited by herbimycin A and by the PI 3-kinase inhibitors
      wortmannin and LY-294002. Preincubation of cells with herbimycin A or PI 3-kinase
      inhibitors also resulted in an inhibition of mitogen-activated protein (MAP)
      kinase p42 and p44 activities as seen on Western blots. In summary, we found that
      1) the maintenance of sustained contraction is dependent on extracellular Ca2+;
      2) ceramide activates a nonreceptor tyrosine kinase pathway through activation of
      pp60(src) and PI 3-kinase; and 3) the converging signals are probably through
      activation of MAP kinase.

PMID- 9756501
TI  - Monochloramine induced DNA fragmentation in gastric cell line MKN45.
AB  - Monochloramine (NH2Cl) is known to be one of the virulence factors in
      Helicobacter pylori-associated gastric mucosal injury. The present study was
      designed to examine NH2Cl-evoked DNA fragmentation in the gastric epithelial cell
      line MKN45. NH2Cl was produced by mixing NH3 with sodium hypochlorite (NaClO).
      MKN45 cells were exposed to NH2Cl, NH3, or NaClO in Hanks' balanced salt
      solution. DNA cleavage was evaluated quantitatively by photometeric enzyme
      immunoassay for the in vitro determination of cytoplasmic mono- and
      oligonucleosomes. Damage to the plasma membrane was assessed by measuring the
      activity of lactate dehydrogenase in the supernatants. Separately, DNA ladder
      formation was performed to confirm the incidence of DNA fragmentation. NH2Cl
      (0.001-0.01 mM) significantly increased the cytoplasmic mono- and
      oligonucleosomes, suggesting the incidence of DNA cleavage. The DNA ladder was
      clearly evoked by NH2Cl. NH2Cl induced a DNA fragmentation, one of the important
      aspects in apoptosis, in the gastric cell line MKN45.

PMID- 9756502
TI  - Hepatocellular expression of glucose-6-phosphatase is unaltered during hepatic
      regeneration.
AB  - Gluconeogenesis and glycogenolysis are essential hepatic functions required for
      glucose homeostasis. During the initial phase of hepatic regeneration, the
      immediate-early genes (IEG) are rapidly expressed, and the IEG RL-1 encodes for
      glucose-6-phosphatase (G-6-Pase). G-6-Pase is a microsomal enzyme essential for
      gluconeogenesis and glycogenolysis. This study employs a partial-hepatectomy
      model to examine the expression and activity of G-6-Pase. After partial
      hepatectomy, rat hepatic G-6-Pase gene expression is transcriptionally regulated,
      and mRNA levels are increased approximately 30-fold. However, in contrast to this
      rapid gene induction, microsomal enzyme activity is unchanged after partial
      hepatectomy. Western blotting demonstrates that microsomal G-6-Pase protein
      expression is also unchanged after partial hepatectomy, and similar results are
      also noted in whole liver homogenate. Thus, despite marked induction in gene
      expression of the IEG G-6-Pase after partial hepatectomy, protein expression and
      enzyme activity remain unchanged. These data indicate that, although this
      hepatocyte IEG is transcriptionally regulated, the physiologically important
      level of regulation is posttranscriptional. This highlights the importance of
      correlating gene expression of IEG with protein expression and physiological
      function.

PMID- 9756503
TI  - Cystatin A expression reduces bile salt-induced apoptosis in a rat hepatoma cell
      line.
AB  - We have previously demonstrated abrogation of bile salt-induced apoptosis by
      cathepsin B inhibitors. However, caspases have been strongly implicated in
      apoptosis, and the mechanistic interface between caspase and cathepsin B
      activation is unclear. Thus our aims were to determine the mechanistic
      relationship between caspases and cathepsin B in bile salt-induced apoptosis in a
      rat hepatoma cell line. Expression of cystatin A was used to inhibit cathepsin B,
      whereas Z-Val-Ala-Asp-fluoromethyl ketone (Z-VAD-FMK) was used to inhibit
      caspases. Cystatin A expression prevented cathepsin B activation and apoptosis
      during treatment with glycochenodeoxycholate (GCDC), a toxic bile salt. Caspase N
      acetyl-Asp-Glu-Val-Asp-7-amino-4-methylcoumarin (DEVD-AMC) hydrolytic activity
      increased in both wild-type and cystatin A-transfected cells treated with GCDC,
      demonstrating caspase activation despite inhibition of cathepsin B. In contrast,
      Z-VAD-FMK blocked both DEVD-AMC hydrolytic activity and cathepsin B activity
      during GCDC treatment. Our data demonstrate that 1) bile salt-induced apoptosis
      can be inhibited by the cystatin A transgene and 2) caspase and cathepsin B
      activation are linked mechanistically with cathepsin B downstream of caspases.

PMID- 9756504
TI  - Effect of VIP and PACAP on basal release of serotonin from isolated vascularly
      and luminally perfused rat duodenum.
AB  - The effect of vasoactive intestinal polypeptide (VIP), pituitary adenylate
      cyclase-activating peptide-38 (PACAP-38), and PACAP-27 on the release of
      serotonin (5-HT) into the intestinal lumen and the portal circulation was studied
      by using in vivo isolated vascularly and luminally perfused rat duodenum. 5-HT
      levels were determined by HPLC. VIP, PACAP-38, and PACAP-27 reduced the luminal
      release of 5-HT but did not affect the vascular release of 5-HT. The inhibitory
      effect caused by VIP, PACAP-38, and PACAP-27 was not affected by either atropine,
      hexamethonium, TTX, or TTX plus ACh, but it was completely antagonized by the
      nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA). The VIP
      receptor antagonist VIP-(10-28) blocked the effects of VIP, PACAP-38, and PACAP
      27. These results suggest that VIP and PACAP exert a direct inhibitory effect on
      the luminal release of 5-HT from the enterochromaffin (EC) cells via a common
      receptor site on the EC cells and that this effect is mediated by NO but not by
      cholinergic pathways. A single injection of TTX, atropine, or hexamethonium
      reduced the luminal release of 5-HT, whereas a single injection of VIP-(10-28)
      stimulated the luminal release of 5-HT and this effect was antagonized by
      atropine, hexamethonium, or TTX. These results suggest that EC cells may receive
      the direct innervation of cholinergic neurons as well as VIP and/or PACAP
      neurons, with the former exerting a tonic stimulatory influence and the latter
      exerting a tonic inhibitory influence on 5-HT release into the intestinal lumen.

PMID- 9756505
TI  - Regulation of c-Jun NH2-terminal kinases in isolated canine gastric parietal
      cells.
AB  - c-Jun NH2-terminal kinases (JNKs) are protein kinases that are activated by a
      wide variety of extracellular signals. This study investigated the expression and
      regulation of JNKs in isolated gastric canine parietal cells. Western blot
      analysis of cell lysates from highly purified (>95%) parietal cells with an
      antibody recognizing JNK1 and to a lesser degree JNK2 revealed the presence of
      two bands of 46 and 54 kDa, respectively. JNK1 activity was quantitated by
      immunoprecipitation and in-gel kinase assays. Of the different agents tested,
      carbachol was the most potent inducer of JNK1 activity, whereas histamine and
      epidermal growth factor induced weaker responses. The proinflammatory cytokine
      tumor necrosis factor-alpha stimulated JNK1 but had no effect on extracellular
      signal-regulated kinase (ERK2) induction, suggesting that activation of JNK1
      might represent an important event in mediation of the inflammatory response in
      the stomach. The action of carbachol was dose (0.1-100 microM) and time
      dependent, with a maximal stimulatory effect (fourfold) detected after 30 min of
      incubation and sustained for 2 h. Addition of the specific protein kinase C (PKC)
      inhibitor GF109203X did not affect the stimulatory action of carbachol. The
      intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N', N'-tetraacetic
      acid-AM inhibited carbachol induction of JNK1 activity by 60%. Thapsigargin (1
      microM), an intracellular Ca2+-rising agent, induced JNK1 activity more than
      threefold. Carbachol activation of JNK1 resulted in induction of c-Jun (protein)
      transcriptional activity and in stimulation of parietal cell mRNA content of c
      jun. In conclusion, our data indicate that carbachol induces JNK activity in
      gastric parietal cells via intracellular Ca2+-dependent, PKC-independent
      pathways, leading to induction of c-jun gene expression via phosphorylation and
      transcriptional activation of c-Jun.

PMID- 9756506
TI  - Glutathione depletion is associated with decreased Bcl-2 expression and increased
      apoptosis in cholangiocytes.
AB  - Cholangiocytes are the target of a group of liver diseases termed the
      cholangiopathies that include conditions characterized by periductal inflammation
      and cholangiocyte apoptosis. Because inflammation is associated with oxidative
      stress, we developed the hypothesis that cholangiocytes exposed to oxidative
      stress will be depleted of endogenous cytoprotective molecules, leading to
      cholangiocyte apoptosis. To begin to test this hypothesis, we explored the
      relationships among glutathione (GSH) depletion, expression of Bcl-2 (a
      protooncogene that inhibits apoptosis), and apoptosis in a nonmalignant human
      cholangiocyte cell line. Monolayers of human bile duct epithelial cells, derived
      from normal liver and immortalized by SV40 transformation, were depleted of GSH
      using buthionine sulfoximine (BSO). Bcl-2 expression was assessed by quantitative
      immunoblot analysis, and apoptosis quantified by fluorescence microscopy using
      the DNA binding dye 4', 6'-diamidino-2-phenylindole. Bcl-2 message was assessed
      by RNase protection assay, and Bcl-2 protein synthesis and half-life by pulse
      chase analysis. Exposure of human cholangiocytes in culture to BSO reduced GSH
      levels by 93 +/- 3% (P < 0.01). In addition, treatment of cholangiocytes with BSO
      reduced Bcl-2 levels by 87 +/- 2% (P < 0.01) and was associated with a time
      dependent increase in the number of cells undergoing apoptosis; approximately 11
      +/- 1% of cultured cells demonstrated morphological changes of apoptosis by 72 h
      compared with 1.5 +/- 0.1% in untreated cholangiocytes (P < 0. 01). Maintenance
      of GSH levels by addition of glutathione ethyl ester in the presence of BSO
      blocked the BSO-associated increase in apoptosis in BSO-treated cholangiocytes
      and also prevented the decrease in Bcl-2 protein. BSO treatment of cholangiocytes
      did not change steady-state levels of bcl-2 mRNA or Bcl-2 protein synthesis.
      However, Bcl-2 protein half-life decreased 57% in BSO-treated vs. untreated
      cells. Our results using a human cholangiocyte cell line demonstrate that
      reduction in the cellular levels of an antioxidant such as GSH results in
      increased degradation of Bcl-2 protein and an increase in apoptosis. These data
      provide a mechanistic link between the consequences of oxidative stress and
      cholangiocyte apoptosis, an observation that may be important in the pathogenesis
      of the inflammatory cholangiopathies.

PMID- 9756507
TI  - Effects of sustained flow reduction on postnatal intestinal circulation.
AB  - Studies were conducted to determine the effect of mechanically induced sustained
      flow reduction on intestinal hemodynamics and oxygenation in 3- and 35-day-old
      swine. In vitro gut loops were perfused under controlled-pressure conditions from
      an oxygenated blood reservoir at age-appropriate perfusion pressures; pressure
      was rapidly reduced to a level that lowered flow rate to approximately 50% of its
      baseline value, and pressure was then kept at that level for 2 h. In 3-day-old
      intestine, vascular resistance (Ri) increased by 20% immediately after pressure
      and flow reduction but then stabilized for 3-4 min; thereafter, flow began to
      decrease despite maintenance of perfusion pressure, so that Ri increased an
      additional 15% by 30 min after flow reduction. Flow continued to diminish over
      the next 90 min, though at much slower rate. Intestine from 35-day-old swine
      demonstrated an immediate increase in Ri after pressure and flow reduction, but
      thereafter Ri increased very little. The protocol was repeated within in vitro
      gut loops perfused under controlled-flow conditions, and within autoperfused,
      innervated gut loops developed in vivo and similar observations were made in both
      preparations. In 3-day-old intestine, pretreatment with the L-arginine analog
      Nomega-monomethyl-L-arginine (10(-4) M) had no effect on the immediate rise in
      resistance occurring in the first 1 min but substantially attenuated the
      subsequent slow, progressive rise noted thereafter. Pretreatment with the
      angiotensin 1A receptor antagonist losartan (2 x 10(-6) M) had no effect on
      hemodynamic changes during the first 60 min after mechanical perfusion pressure
      reduction but attenuated the very slight increase in resistance noted during the
      final 60 min of the protocol. The postnatal intestinal circulation demonstrates
      progressive vasoconstriction when its flow rate is mechanically reduced in a
      sustained manner, and this effect is age specific, occurring in 3- but not 35-day
      old swine. These changes in gut vascular resistance may be consequent to loss of
      nitric oxide production and/or local production of angiotensin.

PMID- 9756508
TI  - Involvement of pituitary adenylate cyclase-activating peptide in opossum internal
      anal sphincter relaxation.
AB  - Despite its widespread distribution and significance in the gut, the role of
      pituitary adenylate cyclase-activating peptide (PACAP) in internal anal sphincter
      (IAS) relaxation has not been examined. This study examined the role of PACAP in
      nonadrenergic noncholinergic (NANC) nerve-mediated relaxation of IAS smooth
      muscle. Circular smooth muscle strips from the opossum IAS were prepared for
      measurement of isometric tension. The influence of PACAP and vasoactive
      intestinal peptide (VIP) antagonists and tachyphylaxis on the neurally mediated
      IAS relaxation was examined either separately or in combination. The release of
      these neuropeptides in response to NANC nerve stimulation before and after the
      nitric oxide (NO) synthase inhibitor Nomega-nitro-L-arginine and NO was also
      investigated. Both PACAP and VIP antagonists caused significant attenuation of
      IAS relaxation by NANC nerve stimulation. The combination of the antagonists,
      however, did not have an additive effect on IAS relaxation. VIP tachyphylaxis
      caused significant suppression of IAS relaxation by NANC nerve stimulation. PACAP
      and VIP were found to be released by NANC nerve stimulation and exogenous NO. The
      data suggest the involvement of PACAP in IAS relaxation primarily by the
      activation of PACAP1/VIP receptor and lack of its independent role in the
      relaxation. Furthermore, NO may regulate the presynaptic release of PACAP and
      VIP.

PMID- 9756509
TI  - Characterization of the 5'-flanking region of the murine polymeric IgA receptor
      gene.
AB  - The regulatory elements that control basal and activated transcriptional
      expression of the polymeric IgA receptor gene (pIgR) have not been defined. In
      this study, we performed functional analysis of the murine pIgR 5'-upstream
      region. Transient transfection studies identified the gene's minimal promoter to
      reside within 110 nucleotides upstream from the start of transcription.
      Substitution mutations of this region identified both a putative activator (-78
      to -70) and a repressor (-66 to -52) element. DNase I footprint analysis
      confirmed an area of protection that spans from nucleotides -85 to -62. Mobility
      shift assays of the putative region confirmed binding of upstream stimulatory
      factor 1 (USF1) to an E box element at positions -75 and -70, representing the
      putative enhancer. Overexpression studies using various forms of USF suggest that
      both USF1 and USF2 enhance activity of the pIgR minimal promoter. We report the
      identification and characterization of the murine pIgR minimal promoter, as well
      as the critical role of USF in enhancing its basal level of transcription in Caco
      2 cells.

PMID- 9756510
TI  - Reduced folate derivatives are endogenous substrates for cMOAT in rats.
AB  - We examined the role of the canalicular multispecific organic anion transporter
      (cMOAT) in the biliary excretion of reduced folate derivatives in vivo and in
      vitro using normal [Sprague-Dawley rats (SDR)] and mutant [Eisai
      hyperbilirubinemic rats (EHBR)] rats whose cMOAT is hereditarily deficient. In
      vivo, the biliary excretion of endogenous tetrahydrofolate (H4PteGlu), 5
      methyltetrahydrofolate (5-CH3-H4PteGlu), and 5,10-methylenetetrahydrofolate (5,
      10-CH2-H4PteGlu) in EHBR was reduced to 8.2%, 1.9%, and 5.5% of those in SDR,
      respectively, whereas that of 10-formyltetrahydrofolate (10-HCO-H4PteGlu) was
      detected only in SDR and not in EHBR. Bile drainage caused reduction of
      endogenous plasma folate concentrations in SDR but not in EHBR. In vitro,
      significant ATP-dependent uptake of 3H-labeled 5-CH3-H4PteGlu into canalicular
      membrane vesicles was observed only in SDR. This ATP-dependent uptake was
      saturable with a Michaelis constant (Km) value of 126 microM, which was
      comparable with its inhibitor constant (Ki) value of 121 microM for the ATP
      dependent uptake of a typical cMOAT substrate, 2,4-dinitrophenyl-S-glutathione
      (DNP-SG). Vice versa, DNP-SG inhibited the uptake of 5-CH3-H4PteGlu with a Ki of
      35 microM, which was similar to its Km value. In addition, H4PteGlu and 5, 10-CH2
      H4PteGlu also inhibited the ATP-dependent uptake of DNP-SG. These results
      indicate that 5-CH3-H4PteGlu and other derivatives are transported via cMOAT.
      Therefore, reduced folate derivatives are the first endogenous substrates for
      cMOAT that do not contain glutathione, glucuronide, or sulfate moieties.

PMID- 9756511
TI  - Physiological changes in blood glucose affect appetite and pyloric motility
      during intraduodenal lipid infusion.
AB  - We evaluated the effects of varying blood glucose concentration within the normal
      postprandial range and its interaction with small intestinal nutrients on
      antropyloric motility and appetite. Eight healthy males (19-40 yr) underwent
      paired studies, with a blood glucose level of 5 or 8 mmol/l. Manometry and visual
      analog scales were used to assess motility and appetite, during fasting and
      intraduodenal lipid infusion (1.5 kcal/min). In the fasting state, antral waves
      were suppressed at 8 mmol/l compared with 5 mmol/l (P = 0.018). However, pyloric
      motility was no different between the two blood glucose concentrations. Hunger
      was no different at 5 mmol/l compared with 8 mmol/l, but fullness was greater at
      8 mmol/l (P = 0. 01). During intraduodenal lipid infusion, antral waves were
      suppressed (P < 0.035) and isolated pyloric pressure waves (IPPWs) were
      stimulated (P < 0.02) compared with during the fasting state, with no difference
      between blood glucose concentrations, although the temporal patterning of IPPWs
      varied between blood glucose concentrations. The amplitude of IPPWs was greater
      at 5 mmol/l compared with 8 mmol/l (P < 0.001), and hunger decreased at 8 mmol/l
      compared with 5 mmol/l (P = 0.02). We conclude that "physiological" hyperglycemia
      modifies gastric motor and sensory function and that synergy exists between blood
      glucose concentration and small intestinal nutrients in modulating gastric
      motility and appetite.

PMID- 9756512
TI  - Distension-related responses in circular and longitudinal muscle of the human
      esophagus: an ultrasonographic study.
AB  - Both circular muscles (CM) and longitudinal muscles (LM) of the esophagus
      participate in peristalsis. Various measurement techniques have yielded
      conflicting information as to the temporal correlation between contraction in the
      two muscle layers. High-frequency intraluminal ultrasound (HFIUS) is a novel
      technique to detect contraction of LM and CM of the esophagus. We investigated
      the temporal correlation between the CM and LM contraction during ascending
      excitatory and descending inhibitory reflexes using HFIUS. A manometric catheter
      equipped with two balloons and a 12.5-MHz ultrasound transducer catheter was used
      to study 10 normal healthy subjects. The changes in muscle thickness and
      pressure, proximal and distal to esophageal distension, were recorded at 5 and 10
      cm above the lower esophageal sphincter (LES). The esophageal distension induced
      an increase in pressure and an increase in muscle thickness of both CM and LM
      layers proximal to the distension site. The onset of increase in muscle thickness
      and peak muscle thickness in two layers occurred at the same time. There was a
      close temporal correlation between the changes in pressure and changes in muscle
      thickness. Atropine inhibited the distension-related pressure and muscle
      thickness increase in both layers. Distal to the esophageal distension, there was
      no change in pressure but a decrease in the thickness of the two muscle layers.
      The decrease in muscle thickness of the two layers occurred at the same time. The
      responses of the two muscle layers to distension were similar at 5- and 10-cm
      sites above the LES. HFIUS is a relatively noninvasive technique to study the LM
      layer response during peristalsis in vivo. Our data indicate that the two muscle
      layers may contract and relax together during distension-related peristaltic
      reflexes in the esophagus.

PMID- 9756513
TI  - Anaphylaxis-induced alterations in intestinal motility: role of extrinsic neural
      pathways.
AB  - The roles of mast cells and extrinsic and vagal neural pathways in the
      anaphylaxis-induced alterations in motility observed at sites remote from antigen
      exposure were explored. Rats were sensitized to egg albumin (EA) and prepared
      with 1) electrodes to monitor intestinal myoelectric activity, 2) an isolated
      intestinal loop, and 3) either intact vagal innervation or a subdiaphragmatic
      vagotomy. Fasting myoelectric activity was recorded before and after challenge of
      the jejunum in continuity or the isolated loop with EA or BSA. Intestinal
      segments and the brain stems were processed for mast cell identification
      (intestine) or Fos immunoreactivity (brain stem). EA but not BSA challenge of the
      jejunum or the isolated loop induced altered motility at both sites and diarrhea.
      Granulated mast cells were significantly reduced at the site local to but not
      remote from challenge. Vagotomy did not inhibit antigen-induced alterations in
      motility or diarrhea. The number of Fos-immunoreactive nuclei in vagal sensory or
      motor nuclei was not significantly altered by vagotomy. Thus antigen challenge of
      sensitized animals causes mast cell degranulation only at the site of direct
      challenge but alters motility at sites local and remote from challenge. The
      remote response requires intact extrinsic but not necessarily vagal neural
      pathways.

PMID- 9756514
TI  - Neural mediation of vasoactive intestinal polypeptide inhibitory effect on
      jejunal alanine absorption.
AB  - It was recently shown that vasoactive intestinal polypeptide (VIP) inhibits rat
      jejunal alanine absorption, an effect that was significantly reduced by vagotomy.
      This study assesses the role of capsaicin-sensitive primary afferents (CSPA) and
      the myenteric plexus in the inhibition of rat jejunal alanine absorption by VIP.
      Continuous intravenous infusion of VIP (11.2 ng . kg-1 . min-1) reduced alanine
      absorption by 60% in sham control rats and by 20% in rats neonatally treated with
      capsaicin (P < 0.01). In in vitro experiments, VIP decreased alanine uptake by
      jejunal strips isolated from sham control rats in a dose-dependent manner. In the
      presence of 40 nM VIP, alanine uptake by full-thickness jejunal strips was
      reduced by 54% in sham control rats and by 25% in rats neonatally treated with
      capsaicin (P < 0.001). On the other hand, VIP reduced alanine uptake by mucosal
      scrapings by 25% in sham rats compared with 9% reduction in neonatally treated
      rats. Chemical ablation of the extrinsic innervation and jejunal myenteric
      plexuses by pretreatment with benzalkonium chloride significantly (P < 0.001)
      reduced basal alanine absorption and the inhibitory effect of VIP. Moreover,
      incubation of intestinal strips with tetrodotoxin and atropine reduced
      significantly (P < 0.05) the inhibitory effect of VIP on alanine absorption.
      These data suggest that VIP exerts its inhibitory effect on alanine absorption
      through the CSPA fibers and the myenteric plexus. The neuronal circuitry of this
      inhibitory process may involve cholinergic muscarinic mechanisms.

PMID- 9756515
TI  - 5-HT activates nitric oxide-generating neurons to stimulate chloride secretion in
      guinea pig distal colon.
AB  - The participation of nitric oxide (NO) in serotonin (5-hydroxytryptamine; 5-HT)
      evoked chloride secretion in guinea pig distal colon was examined.
      Submucosal/mucosal segments were mounted in Ussing flux chambers, and an increase
      in short-circuit current (Isc) was used as an index of secretion. Addition of 5
      HT to the serosal side produced a concentration-dependent (10(-7)-10(-5) M)
      increase in Isc caused by chloride secretion. NG-nitro-L-arginine (L-NNA)
      significantly reduced the 5-HT-evoked early (P-1) and late (P-2) responses to
      61.1 and 70.6% of control, respectively. Neurally evoked response was also
      inhibited by L-NNA. The NO donor sodium nitroprusside (SNP, 10(-4) M) increased
      basal Isc mainly because of chloride secretion. The SNP-evoked response was
      significantly reduced by tetrodotoxin but was unchanged by atropine or
      indomethacin. These results suggest that the 5-HT-evoked increase in Isc is
      associated with an NO-generating mechanism. Atropine significantly reduced the 5
      HT (10(-5) M)-evoked P-1 and P-2 responses to 71.8 and 19.7% of control,
      respectively. Simultaneous application of atropine and L-NNA further decreased
      the 5-HT-evoked responses more than either drug alone; application of L-NNA and
      atropine decreased the 5-HT-evoked P-1 and P-2 responses to 68.5 and 39.2% of
      atropine-treated tissues, respectively. These results suggest that noncholinergic
      components of P-1 and P-2 responses are 71.8 and 19.7% of control, respectively,
      and that NO components of P-1 and P-2 responses are 32 and 61%, respectively, of
      the noncholinergic component of the 5-HT-evoked responses. The results provide
      evidence that NO may participate as a noncholinergic mediator of 5-HT-evoked
      chloride secretion in guinea pig distal colon.

PMID- 9756516
TI  - Endothelin-1 inhibits secretin-stimulated ductal secretion by interacting with
      ETA receptors on large cholangiocytes.
AB  - We studied the expression of endothelin-1 (ET-1) receptors (ETA and ETB) and the
      effects of ET-1 on cholangiocyte secretion. The effects of ET-1 on cholangiocyte
      secretion were assessed in normal and bile duct-ligated (BDL) rats by measuring
      1) basal and secretin-induced choleresis in vivo, 2) secretin receptor gene
      expression and cAMP levels in small and large cholangiocytes, and 3) luminal
      expansion in response to secretin in intrahepatic bile duct units (IBDU). ETA and
      ETB receptors were expressed by small and large cholangiocytes. ET-1 had no
      effect on basal bile flow or bicarbonate secretion in normal or BDL rats but
      decreased secretin-induced bicarbonate-rich choleresis in BDL rats. ET-1
      decreased secretin receptor gene expression and secretin-stimulated cAMP
      synthesis in large cholangiocytes and secretin-induced luminal expansion in IBDU
      from normal or BDL rats. The inhibitory effects of ET-1 on secretin-induced cAMP
      synthesis and luminal duct expansion were blocked by specific inhibitors of the
      ETA (BQ-610) receptor. ET-1 inhibits secretin-induced ductal secretion by
      decreasing secretin receptor and cAMP synthesis, two important determinants of
      ductal secretion.

PMID- 9756517
TI  - Rat hepatic stellate cells produce cytokine-induced neutrophil chemoattractant in
      culture and in vivo.
AB  - Hepatic stellate cells are widely recognized for their contribution to liver
      fibrosis. This study investigated whether these cells also promote hepatic
      inflammation by producing neutrophil chemoattractants. Specifically, stellate
      cells were examined as potential sources of cytokine-induced neutrophil
      chemoattractant (CINC), a rat chemokine resembling human interleukin-8. Stellate
      cells from normal rat liver expressed little or no CINC. In culture, CINC mRNA
      was induced rapidly, coinciding with the phenomenon of culture activation. CINC
      mRNA rose 4.6-fold within 3 days and was accompanied by secretion of
      immunoreactive and biologically active CINC protein (4.1 ng . microgram DNA-1 .
      day-1). Studies in vivo demonstrated that CINC could be induced in stellate cells
      during liver injury. CINC mRNA rose significantly (4- to 6-fold) in two models of
      liver disease, both of which cause stellate cell activation. In summary, the data
      indicate that CINC is induced during stellate cell activation in culture and in
      vivo. They suggest that stellate cell-derived CINC can promote hepatic
      inflammation in vivo.

PMID- 9756518
TI  - Localization and secretion of tissue kallikrein in peptidoglycan-induced
      enterocolitis in Lewis rats.
AB  - The plasma kallikrein-kinin system is a mediator of intestinal inflammation
      induced by peptidoglycan-polysaccharide from group A streptococci (PG-APS) in
      rats. In this study we investigated the participation of intestinal tissue
      kallikrein (ITK). Lewis rats were injected intramurally with PG-APS. ITK was
      visualized by immunohistochemical staining. Cecal ITK concentration was measured
      by radioimmunoassay, and gene expression was evaluated by RNase protection assay.
      Kallikrein-binding protein (KBP) was evaluated in plasma by ELISA. Tissue
      kallikrein was identified in cecal goblet cells in both control and PG-APS
      injected rats and in macrophages forming granulomas in inflamed tissues. Cecal
      ITK was significantly lower in acute and chronic phases of inflammation and in
      supernatant from in vitro cultures of inflamed cecum. ITK mRNA levels were not
      significantly different. Plasma KBP levels were significantly reduced in inflamed
      rats. The presence of tissue kallikrein in macrophages suggests participation in
      experimental colitis. The decrease of ITK in the inflamed intestine associated
      with unchanged mRNA levels suggests ITK release during intestinal inflammation.

PMID- 9756519
TI  - A choline-rich diet improves survival in a rat model of endotoxin shock.
AB  - This study investigated whether dietary choline can prevent endotoxin shock.
      Female Sprague-Dawley rats fed chow or chow plus choline chloride (0.025-0.4%)
      for 3 days were given lipopolysaccharide (LPS) via the tail vein. Eighty-three
      percent and 56% of chow-fed rats survived after 2.5 or 5.0 mg/kg LPS,
      respectively. Choline increased survival in a dose-dependent manner, with maximal
      effects observed at 0.4%; this dose of choline prevented mortality completely
      after 2.5 or 5 mg/kg LPS. Choline also improved the microscopic appearance of the
      lungs and blunted increases in serum aspartate aminotransferase levels.
      Intracellular Ca2+ was monitored in liver and lung macrophages during LPS
      exposure. Ca2+ increases in macrophages from choline-fed rats were blunted by 40
      60% compared with chow-fed controls. Feeding choline also blunted tumor necrosis
      factor-alpha production. Feeding glycine, which prevents macrophage activation
      via a chloride channel, in addition to choline was even more effective than
      feeding choline alone, suggesting that glycine and choline act via distinct
      sites. These data are consistent with the hypothesis that choline diminishes
      endotoxin shock by preventing macrophage activation.

PMID- 9756520
TI  - Role of nitric oxide in systemic vasopressin-induced hypothermia.
AB  - It has been reported that arginine vasopressin (AVP) plays a thermoregulatory
      action, but very little is known about the mechanisms involved. In the present
      study, we tested the hypothesis that nitric oxide (NO) plays a role in systemic
      AVP-induced hypothermia. Rectal temperature was measured before and after AVP,
      AVP blocker, or NG-nitro-L-arginine methyl ester (L-NAME; NO synthase inhibitor)
      injection. Control animals received saline injections of the same volume. The
      basal body temperature (Tb) measured in control animals was 36.53 +/- 0.08
      degreesC. We observed a significant (P < 0.05) reduction in Tb to 35.44 +/- 0.19
      degreesC after intravenous injection of AVP (2 micrograms/kg) and to 35.74 +/- 0.
      10 degreesC after intravenous injection of L-NAME (30 mg/kg). The systemic
      injection of the AVP blocker [beta-mercapto-beta, beta
      cyclopentamethylenepropionyl1,O-Et-Tyr2,Val4,Arg8]vasopressin (10 micrograms/kg)
      caused a significant increase in Tb to 37.33 +/- 0.23 degreesC, indicating that
      AVP plays a tonic role by reducing Tb. When the treatments with AVP and L-NAME
      were combined, systemically injected L-NAME blunted AVP-induced hypothermia. To
      assess the role of central thermoregulatory mechanisms, a smaller dose of L-NAME
      (1 mg/kg) was injected into the third cerebral ventricle. Intracerebroventricular
      injection of L-NAME caused an increase in Tb, but when intracerebroventricular L
      NAME was combined with systemic AVP injection (2 micrograms/kg), no change in Tb
      was observed. The data indicate that central NO plays a major role mediating
      systemic AVP-induced hypothermia.

PMID- 9756521
TI  - Effects of aortic nerve stimulation on discharges of sympathetic neurons
      innervating rat tail artery and vein.
AB  - Activity was recorded from postganglionic sympathetic neurons (PSNs) innervating
      either the caudal ventral artery (CVA) or a lateral vein (LV) of the tail
      circulation of anesthetized rats. The study sought to determine whether
      sympathetic activity directed at the CVA and LV was influenced by cardiovascular
      mechanoreceptor afferents and whether this effect was differential. Cardiac
      rhythmicity was not a robust component of either CVA PSN activity or LV PSN
      activity. Stimulation of an aortic nerve with short trains was followed by a
      decreased probability of discharge in both CVA and LV PSNs that was followed by a
      series of peaks that showed a constant periodicity that was not significantly
      different from that revealed by autocorrelogram analysis over the same data set.
      The latter dominant periodicity is referred to in this and related previous
      publications as the T rhythm. Furthermore, blood volume expansion and long-train
      aortic nerve stimulation produced a significant decrease in the frequency of the
      T rhythm. It is concluded that the CVA and LV sympathetic activity can be
      influenced by inputs from cardiovascular mechanoreceptors and that this effect is
      mediated in part by a modulation of the T rhythm.

PMID- 9756522
TI  - Efficacy of exogenous recombinant murine leptin in lean and obese 10- to 12-mo
      old female CD-1 mice.
AB  - Leptin efficacy was compared in obese and lean female CD-1 mice. Body weights in
      these 10- to 12-mo-old mice ranged from 29.7 to 62.0 g, and leptin levels
      correlated with body weight. Mice from the lean and obese ends of the weight
      distribution were treated with daily peripheral leptin injections (1-100 mg/kg)
      for a 33-day period. The half-maximal effective doses for weight loss and fat
      reduction were shifted 0.5-0.7 log to the right for obese mice. Leptin was less
      efficacious at low doses (1-3 mg/kg) in obese mice but equal to or more
      efficacious in obese than lean mice at high doses (30-100 mg/kg). Leptin's
      initial effects on weight loss could be explained by appetite suppression in both
      groups, but its effects on fat reduction were greater in leptin-treated than pair
      fed mice, particularly in the lean group. Leptin also prevented the elevations in
      serum corticosterone and ketones found in pair-fed lean mice. These data allow a
      quantitative comparison of leptin sensitivity in obese vs. lean CD-1 mice and
      suggest that in mice where obesity is a function of outbreeding and age, leptin
      sensitivity is moderately reduced. Furthermore, although appetite suppression has
      a clear role in leptin's effects on body weight, leptin may also have specific
      effects on lipid metabolism and mobilization that are different from the
      metabolic compensations that normally occur with food deprivation.

PMID- 9756523
TI  - Stability of circadian timing with age in Syrian hamsters.
AB  - The causes of age-related disruptions in the timing of human sleep and
      wakefulness are not known but may include changes in both the homeostatic and
      circadian regulation of sleep. In Syrian hamsters the free running period of the
      circadian activity/rest rhythm has been reported to shorten with age. Although
      this has been observed under a variety of experimental conditions, the changes
      have been small and their consistency uncertain. In the present study, the wheel
      running activity/rest rhythm was continuously measured in male Syrian hamsters
      (Mesocricetus auratus) in dim constant light (<1 lx) from 8 wk of age until
      death. Fifteen hamsters survived to at least 90 wk (28%). The average free
      running period of these hamsters did not change with age. In 18 hamsters that
      died between 50 and 88 wk, free running period also did not change before death.
      In contrast to free running period, other measures related to activity level
      changed significantly with age and before death. Despite changes in the
      expression of the activity/rest rhythm, the free running period of the hamster
      circadian pacemaker remained remarkably stable with age.

PMID- 9756524
TI  - Nutrients regulate diamine oxidase release from intestinal mucosa.
AB  - Diamine oxidase is continuously released from the intestinal mucosa and carried
      to the circulation by the lymphatics. The effect of nutrients on this release was
      examined. Rats were prepared with duodenal and intestinal lymph cannulas. Test
      mixtures of lipid emulsions containing triolein, oleic acid, or tricaprylin and
      solutions of carbohydrate and protein were infused into the duodenum. The enzyme
      release and triglyceride transport were determined and in some experiments were
      done in the presence and absence of Pluronic L-81, an inhibitor of chylomicron
      formation, and aminoguanidine, an inhibitor of diamine oxidase activity. The data
      indicate that nonlipid nutrients did not increase diamine oxidase activity in the
      intestinal lymph, but the mucosal tissue content was significantly reduced in the
      distal small intestine, particularly after protein infusion. Triglycerides and
      fatty acids increased diamine oxidase in the intestinal lymph, and the longer
      chain triglyceride was more effective. Inhibition of triglyceride transport did
      not interfere with the enzyme release, and the inhibition of diamine oxidase
      activity had no significant effect on lipid absorption. According to our
      observations, only lipids increase intestinal lymph diamine oxidase. Nonfat
      nutrients appear to increase diamine oxidase in the intestinal lumen. Diamine
      oxidase is not directly required for lipid absorption.

PMID- 9756525
TI  - Leptin does not fully account for the satiety activity of adipose tissue
      conditioned medium.
AB  - To determine whether leptin alone accounts for the satiety activity secreted by
      native adipose tissue, we prepared culture media conditioned by microdissected
      adipose tissue from overfed Long-Evans rats, fa/fa rats, or db/db mice (media A,
      B, and C, respectively). Medium A significantly suppressed food intake following
      intracerebroventricular delivery to Long-Evans rats (2-h chow intake = 68 +/- 5%
      of baseline, P < 0.001). Media B and C significantly suppressed food intake
      following intraperitoneal delivery to ob/ob mice (24-h chow intake = 56 +/- 7% of
      baseline for medium B, P = 0. 001; 4-day chow intake = 78 +/- 3% of baseline for
      medium C, P = 0. 004). Using a leptin receptor-based bioassay, we determined that
      the leptin concentration of medium C was 392 +/- 18 ng/ml. This concentration was
      20-fold lower than the concentration of recombinant murine leptin required to
      produce a similar degree of feeding suppression following 5 days of
      administration to ob/ob mice. Neither medium conditioned by adipose tissue from
      ob/ob mice nor medium conditioned by adipose tissue from fa/fa rats and
      subsequently immunodepleted of leptin had significant satiety activity. We
      conclude that leptin is necessary but not sufficient to account for the satiety
      activity of native adipose tissue, perhaps due to the production by adipocytes of
      a cofactor that augments the ability of leptin to suppress feeding.

PMID- 9756526
TI  - Effects of costimulation of dopamine D1- and D2-like receptors on renal function.
AB  - In vitro studies have suggested that dopamine D1- and D2-like receptors interact
      to inhibit renal sodium transport. We used Z-1046, a dopamine receptor agonist
      with the rank-order potency D3 >/= D4 > D2 > D5 > D1, to test the hypothesis that
      D1- and D2-like receptors interact to inhibit renal sodium transport in vivo in
      anesthetized rats. Increasing doses of Z-1046, administered via the right renal
      artery, increased renal blood flow (RBF), urine flow, and absolute and fractional
      sodium excretion without affecting glomerular filtration rate. For determination
      of the dopamine receptor involved in the renal functional effects of Z-1046,
      another group of rats received Z-1046 at 2 microgram . kg-1 . min-1 (n = 10) in
      the presence or absence of the D2-like receptor antagonist domperidone and/or the
      D1-like antagonist SCH-23390. Domperidone alone had no effect but blocked the Z
      1046-mediated increase in urine flow and sodium excretion; it enhanced the
      increase in RBF after Z-1046. SCH-23390 by itself decreased urine flow and sodium
      excretion without affecting RBF and blocked the diuretic, natriuretic, and renal
      vasodilatory effect of Z-1046. We conclude that the renal vasodilatory effect of
      Z-1046 is D1-like receptor dependent, whereas the diuretic and natriuretic
      effects are both D1- and D2-like receptor dependent.

PMID- 9756527
TI  - Differential arterial baroreflex regulation of renal, lumbar, and adrenal
      sympathetic nerve activity in the rat.
AB  - Lumbar (LSNA), renal (RSNA), or adrenal sympathetic nerve activity (ASNA) is most
      commonly used as an index of sympathetic nerve activity in investigations of
      arterial baroreflex control in the rat. Although differential regulation of
      sympathetic outputs to different organs has been extensively studied, no direct
      and simultaneous comparisons of the full range of baroreflex reactivity have been
      described for these sympathetic outputs. Therefore, we compared steady-state
      sigmoidal baroreflex stimulus-response curves (via phenylephrine-nitroprusside
      infusion) for RSNA recorded simultaneously with LSNA or ASNA in urethan
      chloralose-anesthetized male Sprague-Dawley rats. Characteristics of the
      baroreflex curves differed significantly between all three sympathetic outputs.
      ASNA exhibited the greatest range of baroreflex regulation, the highest upper
      level of activity, and the widest distribution of the gain over a broad range of
      mean arterial pressure (MAP). RSNA exhibited greater gain than LSNA. LSNA showed
      the smallest range and maximal inhibition in comparison to other sympathetic
      outputs. However, all three nerves responded similarly to baroreflex stimulation
      and unloading in the range in MAP close to the operating point. We conclude that
      baroreflex regulation of sympathetic activity shows wide regional variability in
      gain, range, and maximal inhibition. Therefore, the entire stimulus-response
      relationship should be considered in comparing regional sympathetic responses.

PMID- 9756528
TI  - Acidic fibroblast growth factor activates adrenomedullary secretion and
      sympathetic outflow in rats.
AB  - Effects of exogenous acidic fibroblast growth factor (aFGF), which is increased
      in the brain by food intake, on the plasma levels of catecholamines and on
      sympathetic efferent outflow were examined in anesthetized rats. A guide cannula
      was inserted into the cerebral third ventricle, and a vascular indwelling
      catheter was inserted into the right atrium from the jugular vein. Plasma
      epinephrine (Epi) and norepinephrine (NE) increased markedly in a dose-dependent
      manner for up to 120 min after intracerebroventricular or intravenous
      administration of aFGF (6-667 fmol/rat). Concomitant increases occurred in the
      efferent activity in the sympathetic nerves supplying the adrenal, spleen, and
      interscapular brown adipose tissue after the above administrations of aFGF. Both
      intravenous and intracerebroventricular administration of 10 ng basic FGF (bFGF)
      also increased sympathetic adrenal efferent activity and plasma Epi and NE
      concentrations. However, the increases induced by 10 ng bFGF were smaller than
      those induced by 10 ng aFGF. Bilateral splanchnicotomy completely prevented the
      increases in Epi induced by intracerebroventricular or intravenous aFGF but had
      less effect on the increases in NE. Pretreatment with an antibody against
      corticotropin-releasing factor (CRF), given via the intracerebroventricular
      route, significantly attenuated the increases in Epi and NE evoked by
      intracerebroventricular or intravenous administration of aFGF. Hepatic vagotomy
      also greatly reduced the increases in both catecholamines and the increases in
      sympathetic efferent firing rates evoked by intravenous administration of aFGF.
      These findings indicate that 1) aFGF administered intracerebroventricularly
      activates adrenomedullary secretion and sympathetic outflow via CRF release and
      2) aFGF injected intravenously also induces sympathoadrenomedullary activation
      via centrally released CRF. The idea is discussed that sympathetic activation
      induced either by endogenous aFGF after feeding or by exogenously administered
      aFGF may play roles both in energy expenditure after overeating and in the
      modulation of immune functions.

PMID- 9756529
TI  - Differential suppression of upper airway motor activity during carbachol-induced,
      REM sleep-like atonia.
AB  - Microinjections of carbachol into the pontine tegmentum of decerebrate cats have
      been used to study the mechanisms underlying the suppression of postural and
      respiratory motoneuronal activity during the resulting rapid eye movement (REM)
      sleep-like atonia. During REM sleep, distinct respiratory muscles are
      differentially affected; e.g., the activity of the diaphragm shows little
      suppression, whereas the activity of some upper airway muscles is quite strong.
      To determine the pattern of the carbachol-induced changes in the activity of
      different groups of upper airway motoneurons, we simultaneously recorded the
      efferent activity of the recurrent laryngeal nerve (RL), pharyngeal branch of the
      vagus nerve (Phar), and genioglossal branch of the hypoglossal (XII) and phrenic
      (Phr) nerves in 12 decerebrate, paralyzed, vagotomized, and artificially
      ventilated cats. Pontine carbachol caused a stereotyped suppression of the
      spontaneous activity that was significantly larger in Phar expiratory (to 8.3% of
      control) and XII inspiratory motoneurons (to 15%) than in Phr inspiratory (to
      87%), RL inspiratory (to 79%), or RL expiratory motoneurons (to 72%). The
      suppression in upper airway motor output was significantly greater than the
      depression caused by a level of hypocapnia that reduced Phr activity as much as
      carbachol. We conclude that pontine carbachol evokes a stereotyped pattern of
      suppression of upper airway motor activity. Because carbachol evokes a state
      having many neurophysiological characteristics similar to those of REM sleep, it
      is likely that pontine cholinoceptive neurons have similar effects on the
      activity of upper airway motoneurons during both states.

PMID- 9756530
TI  - Role of endothelial carbon monoxide in attenuated vasoreactivity following
      chronic hypoxia.
AB  - Chronic hypoxic exposure has been previously demonstrated to attenuate systemic
      vasoconstrictor activity to a variety of agents. This attenuated responsiveness
      is observed not only in conscious animals but in isolated vascular preparations
      as well. Because hypoxia has been documented to increase heme oxygenase (HO)
      levels and the subsequent production of the vasodilator CO in vitro, we
      hypothesized that the blunted reactivity observed with chronic hypoxia (CH) may
      be in part due to increased HO activity. In thoracic aortic rings from CH rats,
      cumulative dose-response curves to phenylephrine (PE) in the presence of the
      nitric oxide (NO) synthase inhibitor Nomega-nitro-L-arginine (L-NNA) and the HO
      inhibitor zinc protoporphyrin 9 (ZnPPIX) elicited increased contractility
      compared with CH rings treated with only L-NNA. Similar results were observed in
      rings incubated overnight with the HO-inducing agent sodium m-arsenite. In
      contrast, contractile responses in rings from control rats were unaffected by the
      HO inhibitor. Furthermore, endothelium-denuded rings from either control or CH
      rats did not exhibit an increase in reactivity to PE following ZnPPIX incubation.
      ZnPPIX had no effect on relaxant responses to the NO donor S-nitroso-N
      penicillamine, suggesting that its actions were specific to HO inhibition.
      Finally, aortic rings exhibited dose-dependent relaxant responses to exogenous CO
      that were endothelium independent and blocked by an inhibitor of soluble guanylyl
      cyclase. The other products of HO enzyme activity, iron and biliverdin, were
      without effect on vasoreactivity. Thus we conclude that the attenuated
      vasoreactivity to PE following CH is likely to involve the induction of
      endothelial HO and the subsequent enhanced production of CO.

PMID- 9756532
TI  - Continuity between wound macrophage and fibroblast phenotype: analysis of wound
      fibroblast phagocytosis.
AB  - Analysis of phagocytic activity in wound fibroblasts was chosen as a means to
      assess the possible continuity between macrophage and fibroblast phenotypes.
      Fibroblast phagocytosis of uncoated, IgG-coated, or collagen-coated fluorescent
      beads was analyzed by flow cytometry in vivo and in vitro. Phagocytosis of
      fluorescent beads by procollagen I-positive cells (fibroblasts) was evaluated in
      vivo by injecting beads into subcutaneously implanted sponge wounds in
      anesthetized Fisher rats. Phagocytic activity of a purified population of wound
      fibroblasts was measured in vitro and correlated with oxidation state using
      hydroethidium. In the wound environment, 50-60% of the cells that engulfed
      uncoated, IgG-coated, or collagen-coated beads were procollagen I-positive cells
      (i.e., fibroblasts). Procollagen I-positive cells engulfed uncoated and IgG
      coated beads in preference to collagen-coated beads in vivo. Cultured wound
      fibroblasts engulfed uncoated, IgG-coated, and collagen-coated particles. The
      majority of fibroblasts that engulfed beads were in an elevated oxidation state.
      We conclude that substantial fibroblast phagocytosis occurs in the wound, but
      scavenger receptor-mediated fibroblast phagocytosis is different from that of
      macrophages. Additional markers will be helpful in defining the macrophage
      fibroblast continuum.

PMID- 9756533
TI  - Mechanism of suppressed neutrophil mobilization in a mouse model for binge
      drinking: role of glucocorticoids.
AB  - The goals of this study were to determine if suppression of neutrophil
      accumulation and TNF-alpha production in the peritoneal cavity occurs in mice
      exposed to a chemical stressor [ethanol (EtOH)], to evaluate the role of EtOH
      induced increases in endogenous glucocorticoids in any such suppression, and to
      determine if decreased tumor necrosis factor-alpha (TNF-alpha) production is
      responsible for decreases in neutrophil accumulation in EtOH-treated mice. An
      inflammatory response induced in the peritoneal cavity of mice by administration
      of heat-killed Propionibacterium acnes (P. acnes) was suppressed by a single dose
      of EtOH given 1 h before administration of the bacteria, as indicated by
      decreased accumulation of neutrophils in the peritoneal cavity. The concentration
      of TNF-alpha in the peritoneal cavity was also decreased by EtOH, but exogenous
      TNF-alpha did not prevent the suppression of neutrophil accumulation. The
      glucocorticoid antagonist RU-486 did not prevent the suppression of neutrophil
      accumulation in mice treated with EtOH, but RU-486 did block suppression of
      neutrophil accumulation caused by administration of exogenous corticosterone. The
      suppression of neutrophil accumulation caused by exogenous corticosterone was
      less than produced by EtOH. These observations suggest that the increase in
      endogenous corticosterone induced by EtOH may explain some of the suppression of
      neutrophil accumulation, but other neuroendocrine mediators (or EtOH per se) are
      sufficient to cause the full suppressive effect when the action of corticosterone
      is blocked by RU-486. The results also demonstrate that EtOH decreases TNF-alpha
      production, but this is not the mechanism by which neutrophil accumulation is
      decreased in this model.

PMID- 9756531
TI  - Inhibitors of alternative pathways of arachidonate metabolism differentially
      affect fever in mice.
AB  - Inhibitors of cyclooxygenases prevent fever. The purpose of this study was to
      test the hypothesis that selective and dual inhibitors of the other enzyme
      systems of arachidonic acid oxygenation (i.e., lipoxygenase and epoxygenase)
      affect the time course or magnitude of fever in mice. Swiss Webster mice kept at
      30 degreesC ambient temperature were implanted with biotelemeters to monitor body
      temperature. Fever was induced by intraperitoneal injection of lipopolysaccharide
      at doses from 10 micrograms/kg to 2.5 mg/kg. Phenidone (20-30 mg/kg ip), a dual
      lipoxygenase and cyclooxygenase inhibitor, prevented fever in these mice, but
      esculetin (1-10 mg/kg ip), a selective inhibitor of lipoxygenases, did not affect
      fever. Intramuscular injection of nordihydroguaiaretic acid (10-20 mg/kg), a dual
      lipoxygenase and epoxygenase inhibitor, as well as SKF-525A (5 mg/kg ip) and
      clotrimazole (20 mg/kg im), inhibitors of the cytochrome P-450/epoxygenase
      pathway, augmented fever in mice. Indomethacin (5 mg/kg ip), an inhibitor of
      cyclooxygenase, suppressed the exacerbation of fever due to clotrimazole,
      suggesting that the epoxygenase inhibitor-induced potentiation of fever in mice
      is a prostaglandin-mediated effect. From this study, we hypothesize that the
      cytochrome P-450/epoxygenase branch of the arachidonate cascade is involved in
      antipyresis and in controlling the upper limit of fever.

PMID- 9756534
TI  - Alteration of renal function of rats following spaceflight.
AB  - Following spaceflight, changes in renal function of humans have been suggested.
      To assess the effects of readaptation on renal function, urine was collected from
      male rats ( approximately 245 g) over a 2-wk period following a 14-day
      spaceflight. Rats were assigned to three groups: flight animals (n = 6), flight
      controls (n = 6) housed in the flight cages on the ground, and vivarium controls
      (n = 5) housed in standard shoe box cages. Animals were placed into individual
      metabolic cages for urine collection. Urine output was significantly increased
      for 3 days following flight. Excretion rates of Na+ and K+ were increased,
      resulting in an increased osmotic excretion rate. Creatinine excretion rate
      increased over the first two postflight days. Glomerular filtration rate
      increased immediately following spaceflight without changes in plasma creatinine,
      Na+, K+, or osmolality. Increased excretion of solute was thus the result of
      increased delivery and a decreased percent reabsorption of the filtered load.
      Osmolal clearance was increased immediately postflight while free water clearance
      was decreased. In growing rats, the diuresis after short-duration spaceflight is
      the result of an increase in solute excretion with an accompanying reduction in
      free water clearance.

PMID- 9756535
TI  - Role and mechanism of endothelin-B receptors in mediating ET-1-induced
      vasoconstriction in pig skin.
AB  - We investigated the functional importance and signal transduction pathways of
      endothelin (ET)-B receptors in mediating ET-1-induced vasoconstriction in pig
      skin. Skin vasoconstriction was studied by monitoring the perfusion pressure of
      isolated perfused pig skin flaps (6 x 16 cm) at a constant flow rate. Intra
      arterial infusion of the ETA/B receptor agonist ET-1, the ETB receptor agonists
      sarafotoxin 6C (S6c) and BQ-3020, or the thromboxane A2 mimetic U-46619 (n = 4 or
      5) caused a concentration-dependent skin vasoconstriction. The vasoconstrictor
      potency of ET-1 (EC50 3.1 x 10(-9) M) was lower (P < 0.05) than that of S6c (EC50
      1.8 x 10(-9) M) and similar to that of BQ-3020 (EC50 2.6 x 10(-9) M). The
      vasoconstrictor potency of ET-1, S6c, and BQ-3020 was at least 300-fold higher
      than that of U-46619 (EC50 0.9 x 10(-6) M). The skin vasoconstrictor effect of ET
      1 (10(-9)-10(-8) M) was partially inhibited by 10(-5) M BQ-123, an ETA receptor
      antagonist. Further inhibition was achieved with the combination of 10(-5) M BQ
      123 and BQ-788 (an ETB receptor antagonist) or with an ETA/B receptor antagonist
      (10(-5) M bosentan or PD-145065) (n = 5; P < 0.05). In addition, the skin
      vasoconstrictor effect of the ETB receptor agonist BQ-3020 was completely blocked
      by 5 x 10(-6) M BQ-788 and partially inhibited by 5 x 10(-6) M of the
      phospholipase C (PLC) inhibitor 2-nitro-4-carboxyl-N,N-diphenylcarbamate (NCDC),
      an L-type Ca2+ channel antagonist (nifedipine), a protein kinase C (PKC)
      inhibitor (chelerythrine), or removal of Ca2+ from the perfusate (n = 4 or 5; P <
      0.05). The vasoconstrictor effect of S6c was also partially blocked by 5 x 10(-6)
      M of NCDC, nifedipine, or chelerythrine or by removal of Ca2+ from the perfusate
      (n = 4; P < 0. 01). We conclude that ETB receptors play a central role in
      mediating ET-1-induced vasoconstriction in pig skin, and the mechanism probably
      involves L-type Ca2+ channels, PLC, and PKC.

PMID- 9756537
TI  - Hemodynamic and hormonal responses to hemorrhage in conscious rabbits at mid- and
      late gestation.
AB  - This study tests the hypothesis that conscious rabbits late in pregnancy (P), but
      not at midgestation (MP), are less able to maintain arterial pressure during
      hemorrhage. Blood volume (BV) was elevated (P < 0.05) by an average of 13 +/- 4
      (MP) and 35 +/- 3% (P). Rabbits were bled in both the nonpregnant (NP) and P
      state at 2% of the initial BV per minute. The hemorrhage was stopped after
      arterial pressure decreased. In NP rabbits, arterial pressure was well maintained
      near control pressures of 70 +/- 2 mmHg until 38 +/- 2% of the initial BV was
      removed and then rapidly fell to reach a nadir at 35 +/- 2 mmHg. In contrast, in
      P rabbits, basal arterial pressure was lower (61 +/- 2 mmHg; P < 0.05) and
      gradually decreased to below control after <25% of the initial BV was removed.
      Moreover, the rapid hypotensive phase was triggered with a lower percent BV
      removal (33 +/- 2%; P < 0.05). Basal heart rate was higher during P (149 +/- 5
      vs. 189 +/- 9 beats/min; P < 0.05), and reflex increases were delayed. The slope
      of the relationship between arterial pressure and vasopressin was not modified
      during P, although the line was shifted to a lower pressure (P < 0.05). Larger
      increases in plasma renin activity and ANG II concentration were produced during
      hemorrhage in P rabbits. In contrast, no differences in the changes in arterial
      pressure, heart rate, and vasopressin were found between NP and MP rabbits during
      hemorrhage, although increases in renin and ANG II were greater at MP (P < 0.05).
      In summary, although P conscious rabbits are less able to maintain blood pressure
      during hemorrhage, this change is not evident at MP. These data suggest that the
      factors that mediate the P-induced alterations in arterial pressure regulation
      are not operative until late in gestation.

PMID- 9756536
TI  - Role of nitric oxide in adrenal catecholamine secretion in anesthetized dogs.
AB  - We examined the role of nitric oxide (NO) in adrenal catecholamine secretion in
      response to splanchnic nerve stimulation (SNS) and exogenous acetylcholine (ACh)
      in anesthetized dogs. The NO synthase inhibitor Nomega-nitro-L-arginine methyl
      ester (L-NAME), NO donor 3-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1
      propanamin e (NOC 7), and ACh were administered intra-arterially into the adrenal
      gland. The increases in catecholamine output induced by ACh (0.75-3 microgram)
      were enhanced by L-NAME (0.1-1 mg/min) and inhibited by NOC 7 (0.2-2
      microgram/min). Inhibition by NOC 7 (2 microgram/min) was observed during
      treatment with L-NAME (1 mg/min). The increases in catecholamine output induced
      by SNS (1-2 Hz) were inhibited by L-NAME and by NOC 7. No inhibitory effect of
      NOC 7 was observed during treatment with L-NAME. These results suggest that NO
      may play an inhibitory role in the regulation of adrenal catecholamine secretion
      in response to exogenous ACh.

PMID- 9756538
TI  - Treatment of burned rats with insulin-like growth factor I inhibits the catabolic
      response in skeletal muscle.
AB  - Thermal injury is associated with a pronounced catabolic response in skeletal
      muscle, reflecting inhibited protein synthesis and increased protein breakdown,
      in particular myofibrillar protein breakdown. Administration of insulin-like
      growth factor I (IGF-I) has a nitrogen-sparing effect after burn injury, but the
      influence of this treatment on protein turnover rates in skeletal muscle is not
      known. In the present study, we examined the effect of IGF-I on muscle protein
      synthesis and breakdown rates following burn injury in rats. After a 30% total
      body surface area burn injury or sham procedure, rats were treated with a
      continuous infusion of IGF-I (3. 5 or 7 mg . kg-1 . 24 h-1) for 24 h. Protein
      synthesis and breakdown rates were determined in incubated extensor digitorum
      longus muscles. Burn injury resulted in increased total and myofibrillar protein
      breakdown rates and reduced protein synthesis in muscle. The increase in protein
      breakdown rates was blocked by both doses of IGF-I and the burn-induced
      inhibition of muscle protein synthesis was partially reversed by the higher dose
      of the hormone. IGF-I did not influence muscle protein turnover rates in
      nonburned rats. The results suggest that the catabolic response to burn injury in
      skeletal muscle can be inhibited by IGF-I.

PMID- 9756539
TI  - Endothelins inhibit the mineralization of osteoblastic MC3T3-E1 cells through the
      A-type endothelin receptor.
AB  - We examined the effects of various endothelins on the mineralization of mouse
      clonal preosteoblastic MC3T3-E1 cells. MC3T3-E1 cells expressed mRNAs for
      endothelin (ET)-1 and the A-type receptor for ET (ETA). A pharmacological study
      also demonstrated the predominant expression of the ETA receptor. Northern
      blotting analysis revealed that ETs decreased the expression of mRNA for
      osteocalcin, which is a marker protein for the maturation of osteoblastic cells.
      ET-1 also decreased in the deposition of calcium by MC3T3-E1 cells in a dose
      dependent manner and it had an inhibitory effect even at 10(-11) M. The rank
      order of potency of ETs was ET-1 = ET-2 > ET-3. Brief treatment with 10(-7) M ET
      1 on days 6-8 alone suppressed mineralization. ET-1 enhanced the rate of
      production of inositol 1,4, 5-trisphosphate (IP3) in MC3T3-E1 cells, but it had
      no effect on the rate of production of cAMP. Taken together, our data indicate
      that ET-1 might inhibit the mineralization of osteoblastic cells via an
      interaction with the ETA receptor, with generation of IP3 as the intracellular
      signal.

PMID- 9756540
TI  - Ontogeny of hyperphagia in the Zucker (fa/fa) rat.
AB  - The ontogeny of hyperphagic behavior in the Zucker fatty (fa/fa) rat was
      examined. Wild-type, +/fa, and fa/fa pups aged postnatal day 5 (P5), P9, P12,
      P15, and P18 were evaluated using a test that measured ingestive behavior
      independent of the dam. The independent ingestive test consisted of giving pups
      access to a test solution [half-and-half (cream and milk)] on a tissue on the
      floor of a test chamber for 20 min. The latency to ingest and the intake (weight
      gain and percent weight gain) were measured and normalized to +/fa littermates.
      Pups were tested once to eliminate any effects of test experience. fa/fa Pups
      ingested significantly more than lean pups (+/+ and +/fa) on P12, P15, and P18,
      but not on P5 or P9. The latencies of fa/fa pups did not differ significantly
      from the latencies of +/+ pups except on P18, when the latencies of fa/fa pups
      were significantly shorter. The latencies of +/fa pups were significantly longer
      than the latencies of fa/fa or +/+ pups on P5 and P12. These results demonstrate
      that hyperphagia in fa/fa rats emerges between P9 and P12 under the test
      conditions used.

PMID- 9756541
TI  - Dissimilarity of slow-wave activity enhancement by torpor and sleep deprivation
      in a hibernator.
AB  - Sleep regulation processes have been hypothesized to be involved in function and
      timing of arousal episodes in hibernating ground squirrels. We investigated the
      importance of sleep regulation during arousal episodes by sleep deprivation
      experiments. After sleep deprivation of 4, 12, and 24 h, starting 4 h after onset
      of euthermy, a duration-dependent enhancement of slow-wave activity (SWA) of the
      cortical electroencephalogram during non-rapid eye movement sleep was found, as
      expected for normal sleep regulation. When sleep deprivation was applied during
      the initial phase of the arousal episode, in which effects of prior torpor were
      present in undisturbed recordings, no subsequent recurrence of SWA was found. In
      addition, prior torpor induced a reduction in the spectral activity of the sigma
      frequency range (7-14 Hz), which was not observed after sleep deprivation. The
      effects of torpor and sleep deprivation on subsequent SWA appear qualitatively
      different. This indicates that effects of deep torpor on sleep are dissimilar to
      normal sleep regulation.

PMID- 9756542
TI  - Contrasting cardiovascular effects following central and peripheral injections of
      trout galanin in trout.
AB  - Little is known about the role of galanin (Gal) in fish. In the present study,
      cardiovascular effects of central and peripheral administrations of a synthetic
      replicate of trout Gal (tGal) were investigated in the unanesthetized trout.
      Intracerebroventricular injection of 0.1, 0.5, 1.0, and 3.0 nmol/kg body mass of
      the peptide demonstrated that the two highest doses tested produced a significant
      (P < 0.001) and equivalent increase in mean dorsal aortic blood pressure (PDA)
      without changing heart rate (HR). At a dose of 1.0 nmol/kg, the systemic vascular
      resistance (Rs) increased, but no change was detected in cardiac output compared
      with that produced by intracerebroventricular injection of vehicle only. In
      contrast, intra-arterial injections of 0.1, 0.5, and 1.0 nmol/kg body mass of
      tGal produced a dose-dependent decrease in PDA with a threshold dose for
      significant effects observed at a dose of 0.5 nmol/kg. None of the doses tested
      changed HR. At a dose of 1 nmol/kg, a significant decrease in Rs (P < 0.001) was
      the factor responsible for the fall in PDA. Intra-arterial injection of porcine
      Gal (1 nmol/kg) produced a change in PDA similar to that of the same dose of
      tGal, but HR increased slightly. Pretreatments of trout with the cyclooxygenase
      inhibitors indomethacin and meclofenamate did not inhibit the vasodepressor
      effects of tGal. However, after intra-arterial injection of NG-nitro-L-arginine
      methyl ester, an inhibitor of nitric oxide synthase, the hypotensive action of
      Gal was reduced threefold, suggesting the possible involvement of the nitric
      oxide system in mediating the vasodilatory effect of Gal. In conclusion, our
      results have shown that tGal may have contrasting cardiovascular regulatory
      functions in trout depending on whether its site of action is the brain or the
      peripheral circulation.

PMID- 9756543
TI  - Genetic variation in EEG activity during sleep in inbred mice.
AB  - The genetic variation in spontaneous rhythmic electroencephalographic (EEG)
      activity was assessed by the quantitative analysis of the EEG in six inbred mice
      strains. Mean spectral EEG profiles (0-25 Hz) over 24 h were obtained for
      paradoxical sleep (PS), slow-wave sleep (SWS), and wakefulness. A highly
      significant genotype-specific variation was found for theta peak frequency during
      both PS and SWS, which strongly suggests the presence of a gene with a major
      effect. The strain distribution of theta peak frequency during exploratory
      behavior differed from that during sleep. In SWS, the relative contributions of
      delta (1-4 Hz) and sigma (11-15) power to the EEG varied with genotype and power
      in both frequency bands was negatively correlated. In addition, the EEG dynamics
      at state transitions were analyzed with a 4-s resolution. The onset of PS, but
      not that of wakefulness, was preceded by a pronounced peak in high-frequency (>11
      Hz) power. These findings are discussed in terms of the neurophysiological
      mechanisms underlying rhythm generation and their control and modulation by the
      brain stem reticular-activating system.

PMID- 9756544
TI  - Altered expression of type 2 CRH receptor mRNA in the VMH by glucocorticoids and
      starvation.
AB  - In the rat, high-dose corticosterone (Cort) administration, the hypercortisolism
      of starvation, and adrenalectomy are all associated with decreased food intake
      and weight loss. We report here a study of the effects of high-dose Cort
      administration, starvation, and adrenalectomy on two peripheral hormones known to
      influence food intake and energy use, insulin and leptin. We also studied the
      impact of these interventions on the levels of type 2 corticotropin-releasing
      hormone receptor (CRHR-2) mRNA in the hypothalamic paraventricular nucleus (PVN)
      and ventromedial hypothalamus (VMH). The VMH is classically referred to as the
      satiety center because electrical stimulation of the VMH leads to inhibition of
      food intake, whereas CRHR-2 are thought to transduce the profound anorexogenic
      effects of CRH or its related peptide urocortin. Starvation and adrenalectomy
      each lowered plasma insulin and leptin levels and were associated with decrements
      in CRHR-2 mRNA levels in the VMH. Cort administration increased plasma leptin
      levels profoundly, as well as plasma insulin levels and the levels of VMH CRHR-2
      mRNA. Under all experimental conditions, a positive correlation was seen between
      plasma leptin levels and VMH CRHR-2 mRNA. These data suggest that decreased food
      intake and weight loss after high-dose Cort administration at least partially
      depend on the profound impact of Cort on plasma leptin secretion in the rat; they
      suggest, moreover, an additional mechanism for the satiety-inducing effects of
      leptin, namely increasing CRHR-2 in the VMH. The concordance of a fall in plasma
      insulin and leptin levels with the fall in VMH CRHR-2 mRNA levels further
      supports the idea that compensatory responses during starvation and adrenalectomy
      include not only the disinhibiting effects of reduced insulin and leptin levels
      on appetite through already-described mechanisms but also via an effect of leptin
      on VMH CRHR-2. Neither Cort administration, starvation, nor adrenalectomy
      influenced the levels of CRHR-2 mRNA in the PVN, suggesting that these receptors
      are differentially regulated in different hypothalamic regions.

PMID- 9756545
TI  - Cytokines mediate protective stimulation of glucocorticoid output during
      autoimmunity: involvement of IL-1.
AB  - Endogenous glucocorticoid levels are increased during experimental autoimmune
      encephalomyelitis (EAE) in Lewis rats. Although this endocrine response is
      essential for survival, the mechanism that triggers the stimulation of
      glucocorticoid output during the disease remains unknown. We report here that 1)
      after immunization with the encephalitogenic antigen myelin basic protein (MBP),
      increased blood glucocorticoid levels are not only observed in Lewis rats, but
      also in PVG rats, which do not develop EAE; 2) immune cells obtained from animals
      with EAE and stimulated in vitro with MBP produced mediators that increased
      glucocorticoid levels when administered to naive recipients; and 3) acute in vivo
      blockade of interleukin-1 (IL-1) receptors inhibited, to a large extent, the
      increase in corticosterone levels during EAE. These results show that the
      increase in corticosterone levels after immunization with MBP can be dissociated
      from the stress of the paralytic attack that characterizes EAE. Furthermore, they
      indicate that an endocrine response, which is decisive for the prevention or
      moderation of EAE, is mainly the result of the stimulation of the hypothalamic
      pituitary-adrenal axis by cytokines produced during the immune response that
      induces the autoimmune disease.

PMID- 9756546
TI  - Intracellular pH regulation in neurons from chemosensitive and nonchemosensitive
      areas of the medulla.
AB  - Intracellular pH (pHi) regulation was studied in neurons from two chemosensitive
      [nucleus of the solitary tract (NTS) and ventrolateral medulla (VLM)] and two
      nonchemosensitive [hypoglossal (Hyp) and inferior olive (IO)] areas of the
      medulla oblongata. Intrinsic buffering power (betaint) was the same in neurons
      from all regions (46 mM/pH U). Na+/H+ exchange mediated recovery from
      acidification in all neurons [Ritucci, N. A., J. B. Dean, and R. W. Putnam. Am.
      J. Physiol. 273 (Regulatory Integrative Comp. Physiol. 42): R433-R441, 1997]. Cl
      /HCO-3 exchange mediated recovery from alkalinization in VLM, Hyp, and IO neurons
      but was absent from most NTS neurons. The Na+/H+ exchanger from NTS and VLM
      neurons was fully inhibited when extracellular pH (pHo) <7.0, whereas the
      exchanger from Hyp and IO neurons was fully inhibited only when pHo <6.7. The Cl
      /HCO-3 exchanger from VLM, but not Hyp and IO neurons, was inhibited by pHo of
      7.9. These pH regulatory properties resulted in steeper pHi-pHo relationships in
      neurons from chemosensitive regions compared with those from nonchemosensitive
      regions. These differences are consistent with a role for changes of pHi as the
      proximate signal in central chemoreception and changes of pHo in modulating pHi
      changes.

PMID- 9756547
TI  - Differential catecholamine responses to protein intake in healthy and
      hypertensive subjects.
AB  - Protein intake-induced natriuresis previously related to increased urinary
      dopamine excretion was reexamined in an extensive controlled study comparing
      healthy and hypertensive subjects. In healthy subjects, ingestion of 1 g/kg wt
      tuna induced natriuresis that was associated, between postprandial hours 1 and 2,
      with increased plasma tyrosine [191 +/- 13% (mean +/- SE); P < 0.01], 3, 4
      dihydroxyphenylalanine (104 +/- 12%, P < 0.05 in plasma; 162 +/- 20%, P < 0.05 in
      urine), plasma free dopamine (156 +/- 32%; P < 0. 05), and dopamine sulfate (191
      +/- 11%, P < 0.001 in plasma; 199 +/- 15%, P < 0.01 in urine) but affected
      urinary free dopamine excretion only at limits of significance. Hypertensive
      subjects had less (P < 0.02) natriuresis and, despite comparable plasma tyrosine
      and dopamine sulfate increases, no increase in plasma and urinary 3, 4
      dihydroxyphenylalanine and plasma free dopamine. Their plasma and urinary free
      epinephrine responses were less (P < 0.05) than the borderline increases in
      control subjects. Compared with control subjects, they significantly increased
      plasma 3, 4-dihydroxyphenylalanine sulfate (P < 0.05), epinephrine sulfate (P <
      0.05), and the dopamine sulfate-to-free dopamine ratio (P < 0.02). Postprotein
      natriuresis is thus associated with nutritional priming-induced plasma but not
      urinary free dopamine increase. Hypertensive subjects have attenuated natriuretic
      and plasma free dopamine responses and less free epinephrine increase. This may
      partly result from higher circulating 3,4-dihydroxyphenylalanine, dopamine, and
      epinephrine sulfoconjugates leaving fewer free amines for biological actions.

PMID- 9756548
TI  - Role of central catecholaminergic pathways in the actions of endogenous ANG II on
      sympathetic reflexes.
AB  - In the present study, we examined the effect of blockade of the brain stem renin
      angiotensin system on renal sympathetic baroreflexes and chemoreflexes in
      conscious rabbits and examined the role of central catecholaminergic pathways in
      these responses. Eleven rabbits underwent preliminary surgical instrumentation
      and pretreatment with central 6-hydroxydopamine (6-OHDA, 500 micrograms/kg) or
      ascorbic acid 6 wk before the commencement of the experiments. Baroreflex curves
      were determined under conditions of normoxia and hypoxia (10% O2 + 3% CO2) before
      and after central administration of either Ringer solution, the ANG II receptor
      antagonist losartan (10 micrograms), or the angiotensin-converting enzyme
      inhibitor enalaprilat (500 ng) on separate days. Losartan increased the upper
      plateau and the range of the mean arterial pressure (MAP)-renal sympathetic nerve
      activity (RSNA) curve (79 and 78%, respectively) in intact rabbits, whereas this
      effect was not observed in 6-OHDA-pretreated rabbits. Hypoxia elicited an
      increase in resting RSNA (111% in intact rabbits and 74% in 6-OHDA-injected
      rabbits) and elevated the upper plateau of the RSNA-MAP curve in both groups (89%
      in intact rabbits and 114% in 6-OHDA-injected rabbits). During hypoxia, losartan
      and enalaprilat increased the RSNA upper plateau in intact rabbits but had no
      effect in 6-OHDA-pretreated rabbits. No effects on the MAP-heart rate baroreflex
      curves were observed. Thus the effect of losartan to increase RSNA, particularly
      during hypoxia and baroreceptor unloading, being abolished by central
      noradrenergic depletion suggests that the endogenous ANG II which normally causes
      an inhibition of renal sympathetic motoneurons is dependent on the integrity of
      central catecholaminergic pathways.

PMID- 9756549
TI  - Interleukin-4 inhibits spontaneous sleep in rabbits.
AB  - Proinflammatory cytokines, including interleukin-1beta (IL-1beta) and tumor
      necrosis factor-alpha, are involved in sleep regulation. IL-4 is an
      antiinflammatory cytokine that inhibits proinflammatory cytokine production. The
      hypothesis that IL-4 should attenuate sleep was studied by determining the
      effects of IL-4 on rabbit spontaneous sleep. Thirty-six rabbits were used. Four
      doses of IL-4 (0.25, 2.5, 25, and 250 ng) were injected intracerebroventricularly
      during the rest (light) period. One dose of IL-4 (25 ng) was injected during the
      active (dark) cycle. Appropriate time-matched control injections of saline were
      done in the same rabbits on different days. The three highest doses of IL-4
      significantly inhibited spontaneous non-rapid eye movement sleep if IL-4 was
      given during the light cycle. The highest dose of IL-4 (250 ng) also
      significantly decreased rapid eye movement sleep. On the other hand, IL-4
      administered at dark onset had no effect on sleep. The sleep inhibitory
      properties of IL-4 provide additional evidence for the hypothesis that a brain
      cytokine network is involved in the regulation of physiological sleep.

PMID- 9756550
TI  - Poor relationship between arterial [lactate] and leg net release during exercise
      at 4,300 m altitude.
AB  - We evaluated the hypotheses that on acute exposure to hypobaric hypoxia,
      sympathetic stimulation leads to augmented muscle lactate production and
      circulating [lactate] through a beta-adrenergic mechanism and that beta
      adrenergic adaptation to chronic hypoxia is responsible for the blunted exercise
      lactate response after acclimatization to altitude. Five control and 6 beta
      blocked men were studied during rest and exercise at sea level (SL), on acute
      exposure to 4,300 m (A1), and after a 3-wk sojourn at altitude (A2). Exercise was
      by leg cycling at 49% of SL peak O2 consumption (VO2 peak) (65% of altitude VO2
      peak or 87 +/- 2.6 W); beta-blockade was by propranolol (80 mg 3x daily), femoral
      arterial and venous blood was sampled; leg blood flow (Q) was measured by
      thermodilution, leg lactate net release [ = (2) (1-leg Q) venous-arterial
      concentrationL] was calculated, and vastus lateralis needle biopsies were
      obtained. Muscle [lactate] increased with exercise and acute altitude exposure
      but regressed to SL values with acclimatization; beta-blockade had no effect on
      muscle [lactate]. Arterial [lactate] rose during exercise at SL (0.9 +/- 0.1 to
      1.5 +/- 0.3 mM); exercise at A1 produced the greatest arterial [lactate] (4.4 +/-
      0.8 mM), and exercise at A2 an intermediate response (2.1 +/- 0.6 mM). beta
      Blockade reduced circulating [lactate] approximately 45% during exercise under
      all altitude conditions. increased transiently at exercise onset but then
      declined over time under all conditions. Blood and muscle "lactate paradoxes"
      occurred independent of beta-adrenergic influences, and the hypotheses relating
      the blood lactate response at altitude to beta-adrenergic mechanisms are
      rejected. During exercise at altitude, arterial [lactate] is determined by
      factors in addition to hypoxemia, circulating epinephrine, and net lactate
      release from active muscle beds.

PMID- 9756551
TI  - Effects of 17beta-estradiol on sympathetic activity and pressor response to
      phenylephrine in ovariectomized rats.
AB  - The effects of 17beta-estradiol (E2) on sympathetic activity were examined in
      conscious unrestrained ovariectomized rats, instrumented under methohexital
      anesthesia to record mean arterial pressure (MABP), heart rate (HR), renal nerve
      activity (RNA), and splanchnic nerve activity (SNA) 1 day before the experiment.
      Injection of E2 (150 micrograms/kg iv) caused reductions (P < 0.01) in RNA (29 +/
      6%), SNA (25 +/- 2%), and HR (26 +/- 5 beats/min) within 20 min, but MABP
      remained unchanged. Ninety minutes after intravenous injection of E2 or vehicle,
      intravenous infusion of phenylephrine (PE; 6.2 micrograms . min-1 . kg-1) induced
      similar increases in MABP and decreases in HR, RNA, and SNA in both groups. By
      contrast, in rats chronically treated with E2, the pressor response to PE was
      smaller (P < 0.01; 22 +/- 5 mmHg) than in vehicle-treated rats (40 +/- 4 mmHg).
      The changes in HR, RNA, and SNA were similar in both groups, but the ratios of
      changes in HR and SNA to MABP, an index of baroreflex sensitivity, were greater
      in the E2-treated rats. These findings suggest that E2 can act centrally to
      modulate sympathetic function and thereby participate in cardiovascular
      regulation.

PMID- 9756552
TI  - The area postrema does not modulate the long-term salt sensitivity of arterial
      pressure.
AB  - The hindbrain circumventricular organ, the area postrema (AP), receives multiple
      signals linked to body fluid homeostasis. In addition to baroreceptor input, AP
      cells contain receptors for ANG II, vasopressin, and atrial natriuretic peptide.
      Hence, it has been proposed that the AP is critical in long-term adjustments in
      sympathetic outflow in response to changes in dietary NaCl. The present study was
      designed to test the hypothesis that long-term control of arterial pressure over
      a range of dietary NaCl requires an intact AP. Male Sprague-Dawley rats were
      randomly selected for lesion of the AP (APx) or sham lesion. Three months later,
      rats were instrumented with radiotelemetry transmitters for continuous monitoring
      of mean arterial pressure (MAP) and heart rate and were placed in individual
      metabolic cages. Rats were given 1 wk postoperative recovery. The dietary salt
      protocol consisted of a 7-day period of 1.0% NaCl (control), 14 days of 4.0% NaCl
      (high), 7 days of 1.0% NaCl, and finally 14 days of 0.1% NaCl (low). The results
      are reported as the average arterial pressure observed on the last day of the
      given dietary salt period: APx (n = 7) 114 +/- 2 (1.0%), 110 +/- 3 (4.0%), 110 +/
      3 (1.0%), and 114 +/- 4 (0.1%) mmHg; sham (n = 6) 115 +/- 2 (1.0%), 114 +/- 3
      (4.0%), 111 +/- 3 (1. 0%), and 113 +/- 2 (0.1%) mmHg. Neither group of rats
      demonstrated significant changes in MAP throughout the entire dietary salt
      protocol. Furthermore, no significant differences in MAP were detected between
      groups throughout the protocol. All lesions were histologically verified. These
      results suggest that the area postrema plays no role in long-term control of
      arterial pressure during chronic changes in dietary salt.

PMID- 9756553
TI  - Slow restoration of LH pulsatility by refeeding in energetically disrupted women.
AB  - In other energy-restricted mammals, a single large meal restores luteinizing
      hormone (LH) pulsatility within a few hours. To determine whether this is so in
      women, we measured LH pulsatility during the 5th day of low energy availability
      [dietary energy intake - exercise energy expenditure = 10 kcal . kg lean body
      mass (LBM)-1 . day-1] and during a 6th day of aggressive refeeding (90 kcal . kg
      LBM-1 . day-1) in 15 meals providing 4,100 kcal for an energy availability of 75
      kcal . kg LBM-1 . day-1. Low energy availability raised beta-hydroxybutyrate
      1,000% (P < 0.001) and reduced plasma glucose 15% (P < 0.01), insulin 63% (P <
      0.001), and triiodothyronine 22% (P < 0.005). In five of eight subjects, low
      energy availability also unambiguously suppressed LH pulse frequency 57% to 8.2
      +/- 1.5 pulses/24 h (P < 10(-4)) and raised LH pulse amplitude 94% to 3.1 +/- 0.3
      IU/l (P < 10(-4)), levels below the 5th and above the 95th percentile,
      respectively, in energy-balanced women. Aggressive refeeding restored beta
      hydroxybutyrate, glucose, and insulin, but not triiodothyronine. In the five
      women with unambiguously disrupted LH pulsatility, aggressive refeeding had no
      effect on LH pulse amplitude (P > 0.9) and raised LH pulse frequency only
      slightly (2.4 +/- 0.6 pulses/24 h, P = 0.04) and not above the fifth percentile.
      This striking contrast between women and other mammals may be another clue to the
      unidentified mechanism mediating the effect of energy availability on LH
      pulsatility.

PMID- 9756554
TI  - N-acetylcysteine does not affect the lymphocyte proliferation and natural killer
      cell activity responses to exercise.
AB  - This study evaluated whether N-acetylcysteine (NAC) attenuates the reduced
      lymphocyte proliferation and natural killer (NK) cell activity responses to
      exercise in humans. Fourteen oarsmen were double-blind randomized to either NAC
      (6 g daily for 3 days) or placebo groups. During 6-min "all-out" ergometer
      rowing, the concentration of lymphocytes in the peripheral blood increased, with
      no significant difference between NAC and placebo as reflected in lymphocyte
      subsets: CD4(+), CD8(+), CD16(+), and CD19(+) cells. The phytohemagglutinin
      stimulated lymphocyte proliferation decreased from 9,112 +/- 2,865 to 5,851 +/-
      1,588 cpm (P < 0.05), but it was not affected by NAC. During exercise, the NK
      cell activity was elevated from 17 +/- 3 to 38 +/- 4% and it decreased to 7 +/-
      1% below the resting value 2 h into recovery. Yet, when evaluated as lytic units
      per CD16(+) cell, the NK cell activity decreased during and after exercise
      without a significant effect of NAC. We conclude that NAC does not attenuate the
      reduction in lymphocyte proliferation and NK cell activity associated with
      intense exercise.

PMID- 9756555
TI  - Differential regulation of uncoupling protein gene homologues in multiple tissues
      of hibernating ground squirrels.
AB  - Nonshivering thermogenesis in brown adipose tissue (BAT) provides heat through
      activation of a mitochondrial uncoupling protein (UCP1), which causes futile
      electron transport cycles without the production of ATP. Recent discovery of two
      molecular homologues, UCP2, expressed in multiple tissues, and UCP3, expressed in
      muscle, has resulted in investigation of their roles in thermoregulatory
      physiology and energy balance. To determine the expression pattern of Ucp
      homologues in hibernating mammals, we compared relative mRNA levels of Ucp1, -2,
      and -3 in BAT, white adipose tissue (WAT), and skeletal muscle of arctic ground
      squirrels (Spermophilus parryii) hibernating at different ambient and body
      temperatures, with levels determined in tissues from ground squirrels not in
      hibernation. Here we report significant increases in mRNA levels for Ucp2 in WAT
      (1. 6-fold) and Ucp3 in skeletal muscle (3-fold) during hibernation. These
      results indicate the potential for a role of UCP2 and UCP3 in thermal homeostasis
      during hibernation and indicate that parallel mechanisms and multiple tissues
      could be important for nonshivering thermoregulation in mammals.

PMID- 9756556
TI  - Renal denervation supersensitivity revisited.
AB  - To determine whether the chronically denervated kidney is supersensitive to
      either physiological or pathophysiological plasma levels of norepinephrine (NE),
      studies were conducted in conscious dogs subjected to unilateral renal
      denervation and surgical division of the urinary bladder into hemibladders to
      allow separate 24-h urine collection from denervated and innervated kidneys.
      Plasma NE concentration was increased by chronic infusion of NE (4-5 days) at
      rates of 25, 100, and 200 ng . kg-1 . min-1. Twenty-four-hour control values for
      mean arterial pressure (MAP), plasma NE concentration, and ratios for urinary
      sodium and potassium excretion from denervated and innervated kidneys (Den/Inn)
      were 94 +/- 4 mmHg, 145 +/- 24 pg/ml, 1.05 +/- 0.05, and 0.97 +/- 0.07,
      respectively. With infusions of NE producing plasma levels of NE of up to
      approximately 3,000 pg/ml or plasma concentrations of NE at least threefold
      greater than present under most pathophysiological conditions and during acute
      activation of the sympathetic nervous system, there were no significant long-term
      changes in MAP or relative excretion rates of sodium and potassium from
      denervated and innervated kidneys. In marked contrast, pharmacological plasma
      levels of NE ( approximately 7,000 pg/ml) produced chronic increases in MAP (to
      116 +/- 2% of control) and sustained reductions in Den/Inn for urinary sodium and
      potassium excretion to 57 +/- 4 and 68 +/- 5% of control, respectively,
      indicating a lower excretion rate of these electrolytes from denervated vs.
      innervated kidneys. We conclude that the chronically denervated kidney does not
      exhibit an exaggerated antinatriuretic response to either physiological or
      pathophysiological levels of circulating NE. It is therefore unlikely that renal
      denervation supersensitivity is a confounding issue in studies employing chronic
      renal denervation to elucidate the role of the renal nerves in the regulation of
      sodium excretion.

PMID- 9756557
TI  - Heterogeneous neurochemical responses to different stressors: a test of Selye's
      doctrine of nonspecificity.
AB  - Selye defined stress as the nonspecific response of the body to any demand.
      Stressors elicit both pituitary-adrenocortical and sympathoadrenomedullary
      responses. One can test Selye's concept by comparing magnitudes of responses at
      different stress intensities and assuming that the magnitudes vary with stress
      intensity, with the prediction that, at different stress intensities, ratios of
      increments neuroendocrine responses should be the same. We measured arterial
      plasma ACTH, norepinephrine, and epinephrine in conscious rats after hemorrhage,
      intravenous insulin, subctaneous formaldehyde solution, cold, or immobilization.
      Relative to ACTH increments, cold evoked large norepinephrine responses, insulin
      large epinephrine responses, and hemorrhage small norepinephrine and epinephrine
      responses, whereas immobilization elicited large increases in levels of all three
      compounds. The ACTH response to 25% hemorrhage exceeded five times that to 10%,
      and the epinephrine response to 25% hemorrhage was two times that to 10%. The
      ACTH response to 4% formaldehyde solution was two times that to 1%, and the
      epinephrine response to 4% formaldehyde solution exceeded four times that to 1%.
      These results are inconsistent with Selye's doctrine of nonspecificity and the
      existence of a unitary "stress syndrome," and they are more consistent with the
      concept that each stressor has its own central neurochemical and peripheral
      neuroendocrine "signature."

PMID- 9756559
TI  - Myostatin expression in porcine tissues: tissue specificity and developmental and
      postnatal regulation.
AB  - The objective of this study was to establish the developmental pattern and tissue
      specificity of porcine myostatin expression and to evaluate expression in
      skeletal muscle during circumstances in which muscle growth was altered. Northern
      blot analysis revealed two transcripts (1.5 and 0.8 kb). Myostatin mRNA was
      detected in whole fetuses at 21 and 35 days and was markedly increased (P < 0.05)
      by 49 days. At birth, mRNA abundance in longissimus muscle had declined
      significantly (P < 0.05) from that at day 105 of gestation and continued to
      decrease (P < 0.05) to its lowest level 2 wk postnatally (4 kg body wt).
      Myostatin expression was higher (P < 0. 05) at 55, 107, and 162 kg body wt than
      at 4 kg body wt. Postnatally, myostatin mRNA was detected in skeletal muscle and
      mammary gland. Expression at birth was 65% higher (P < 0.04) in longissimus
      muscle of low-birth-weight piglets (0.57 +/- 0.052 kg body wt) vs. normal (1.37
      +/- 0.077 kg body wt) littermates, irrespective of gender. However, suppression
      of longissimus muscle growth by food deprivation (3 days) did not alter (P >
      0.15) myostatin expression in either 4- or 7-wk-old piglets. Additionally,
      myostatin mRNA abundance was not changed by porcine growth hormone administration
      in growing animals. These data indicate that myostatin expression in skeletal
      muscle peaks prenatally and that greater expression is associated with low birth
      weight. Expression in mammary gland indicates a possible role for myostatin in
      mammary gland development and/or lactation.

PMID- 9756558
TI  - NG-hydroxy-L-arginine and nitric oxide inhibit Caco-2 tumor cell proliferation by
      distinct mechanisms.
AB  - The objective of this study was to elucidate the role and mechanism of nitric
      oxide (NO) synthase (NOS) in modulating the growth of the Caco-2 human colon
      carcinoma cell line. The two novel observations reported here are, first, that NG
      hydroxy-L-arginine (NOHA) inhibits Caco-2 tumor cell proliferation, likely by
      inhibiting arginase activity, and, second, that NO causes cytostasis by
      mechanisms that might involve inhibition of ornithine decarboxylase (ODC)
      activity. Both arginase and ODC are enzymes involved in the conversion of
      arginine to polyamines required for cell proliferation. Cell growth was monitored
      by cell count, cell protein analysis, and DNA synthesis. NOHA (1-30 microM) and
      NO in the form of DETA/NO (1-30 microM) inhibited cell proliferation by 30-85%.
      The cytostatic effect of NOHA was prevented by addition of excess ornithine,
      putrescine, spermidine, or spermine to cell cultures, whereas the cytostatic
      effect of NO (DETA/NO) and alpha-difluoromethylornithine (ODC inhibitor) was
      unaffected by ornithine but was prevented by putrescine, spermidine, or spermine.
      The cytostatic effect of NOHA appeared to be independent of its conversion to NO,
      and the effect of NO appeared to be independent of cGMP. NOHA inhibited urea
      production by Caco-2 cells and inhibited arginase catalytic activity (85% at 3
      microM), whereas NO (DEA/NO and SNAP) inhibited ODC activity (>/=60% at 30
      microM) without affecting arginase activity. Coculture of Caco-2 cells with
      lipopolysaccharide/cytokine-activated rat aortic endothelial cells markedly
      slowed Caco-2 cell proliferation, and this was blocked by NOS inhibitors. These
      observations that NOHA and NO may inhibit sequential steps in the arginine
      polyamine pathway suggest a novel biological role for NOS in the inhibition of
      cell proliferation of certain tumor cells and possibly other cell types.

PMID- 9756560
TI  - Sympathetic nerve activity during natural stimulation of horizontal semicircular
      canals in humans.
AB  - We have shown that static head-down neck flexion elicits increases in muscle
      (MSNA) but not skin sympathetic nerve activity (SSNA) in humans. These findings
      suggest that stimulation of the otolith organs causes differential sympathetic
      outflow to vascular beds. The purpose of the present study was to determine
      whether yaw head rotation (YHR), which stimulates the horizontal semicircular
      canals, elicits sympathetic nerve responses. To test this question, we recorded
      MSNA (n = 33) and SSNA (n = 25) before and during 3 min of sinusoidal YHR
      performed at 0.1, 0.6, and 1.0 Hz. At all frequencies, YHR elicited no
      significant changes in heart rate and mean arterial pressure. Likewise, YHR did
      not significantly change either MSNA or SSNA at all frequencies. Our results
      indicate that stimulation of the horizontal semicircular canals by YHR does not
      alter SNA to either muscle or skin. Moreover, these results provide evidence to
      support the concept that the otolith organs but not the horizontal semicircular
      canals participate in the regulation of SNA in humans.

PMID- 9756561
TI  - Altered regulation of bladder nerve growth factor and neurally mediated
      hyperactive voiding.
AB  - Elevated bladder smooth muscle cell (BSMC) nerve growth factor (NGF) secretion
      and related neuroplasticity are associated with hyperactive voiding in
      spontaneously hypertensive rats (SHRs: hypertensive, behaviorally hyperactive),
      compared with control Wistar-Kyotos (WKYs). We used two inbred strains (WKHT:
      hypertensive; WKHA: hyperactive) to further investigate this phenomenon. WKHA
      BSMCs secreted higher basal levels of NGF than WKHT BSMCs. Antagonists did
      inhibit NGF output in WKHA but not WKHT cultures. Thus augmented basal secretion
      of NGF cosegregates with a hyperactive phenotype, whereas a lack of regulatory
      inhibition of NGF output cosegregates with a hypertensive phenotype. Bladder
      norepinephrine content paralleled NGF content, with WKHTs > SHRs > WKHAs > WKYs,
      providing evidence that a lack of inhibition is the greatest contributor to
      elevated bladder NGF and noradrenergic innervation. Protein kinase C (PKC)
      agonists affected NGF production differentially depending on strain, suggesting
      that altered PKC signaling may contribute to strain differences in NGF secretion.
      Finally, 6-h voiding frequency differed between the strains, with SHRs > WKHTs =
      WKHAs > WKYs. Thus aspects of both the hypertensive and hyperactive phenotypes
      may be associated with elevated SHR bladder NGF and hyperactive voiding.

PMID- 9756562
TI  - Uncoupling of the autonomic and cardiovascular systems in acute brain injury.
AB  - We hypothesized that acute brain injury results in decreased heart rate (HR)
      variability and baroreflex sensitivity indicative of uncoupling of the autonomic
      and cardiovascular systems and that the degree of uncoupling should be
      proportional to the degree of neurological injury. We used HR and blood pressure
      (BP) power spectral analysis to measure neuroautonomic regulation of HR and BP
      and the transfer function magnitude (TF) between BP and HR as a measure of
      baroreflex modulation of HR. In 24 brain-injured patients [anoxic/ischemic injury
      (n = 7), multiple trauma (n = 6), head trauma (n = 5), central nervous system
      infection (n = 4), and intracranial hemorrhage (n = 2)], neurological injury and
      survival was associated with low-frequency (0.01-0.15 Hz) HR and BP power and TF.
      Brain-dead patients showed decreased low-frequency HR power [0. 51 +/- 0.36 (SE)
      vs. 2.54 +/- 0.14 beats/min2, P = 0.03] and TF [0. 61 +/- 0.16 (SE) vs. 1.29 +/-
      0.07 beats . min-1 . mmHg-1, P = 0.05] compared with non-brain-dead patients. We
      conclude that 1) severity of neurological injury and outcome are inversely
      associated with HR and BP variability and 2) there is direct evidence for
      cardiovascular and autonomic uncoupling in acute brain injury with complete
      uncoupling during brain death.

PMID- 9756563
TI  - Chemical specificities and intestinal distributions of nutrient-driven satiety.
AB  - We measured intakes of sham- and naturally feeding rats during gut perfusions of
      nutrients. Our objectives were to determine 1) which nutrient products in gut
      lumen suppressed intakes; 2) how suppression by various nutrients is distributed
      along gut; and 3) whether time courses of suppression were similar among
      different nutrients. We found that satiating nutrients consisted of fatty acids
      only longer than 10 carbons, of monomeric carbohydrates only with affinity for
      the glucose transporter, and, among several amino acids, of only phenylalanine
      and tryptophan. Dimeric maltose had about the same potency as an isocaloric
      mixture of longer glucose polymers; since responses to either were blocked by a
      glucosidase inhibitor, each probably acted after hydrolysis to free glucose.
      Effective nutrients suppressed intakes about equally on infusion into duodenum
      vs. midgut, and the same nutrients also suppressed intakes when infused into
      colon. Food intakes were suppressed only while maltose was infused, not after it
      was stopped, but suppression persisted for 2 h after stopping perfusions with
      fatty or amino acids.

PMID- 9756564
TI  - Length of intestinal contact on nutrient-driven satiety.
AB  - Chemosensors throughout small bowel and colon inhibit food intakes when contacted
      by monomeric nutrients. We postulated that calorie-dependent inhibition of food
      intakes depended on additions of feedbacks from sensors in proximal and distal
      bowel contacted after high intakes of nutrients. Therefore, we determined how
      feedback from sensors in proximal gut interacted with feedback from
      simultaneously contacted sensors in distal bowel and whether suppression of
      nutrient intakes by intestinally perfused nutrients depended on length of gut
      contacted. Suppression of food intakes by maltose simply added to that from
      dodecanoate when both were present together either in proximal or distal small
      bowel. When dodecanoate was infused into proximal gut while maltose was infused
      distally, suppression of intake was threefold higher and was thus potentiated.
      Limiting contact of slowly absorbed lactose or oleate to 35 cm of jejunum nearly
      abolished the satiating potencies each exhibited during access to whole gut. The
      observations were consistent with our hypothesis.

PMID- 9756566
TI  - Neuronal cell bodies in paraventricular nucleus affect renal hemodynamics and
      excretion via the renal nerves.
AB  - Several lines of evidence support the existence of an oligosynaptic projection
      from the paraventricular nucleus of the hypothalamus (PVN) to the kidney in the
      rat. We sought to provide evidence that this neural pathway is capable of
      influencing renal function in rats. Bilateral microinjections of bicuculline
      (Bic; 1 nmol) into the PVN decreased glomerular filtration rate (59%), effective
      renal plasma flow (71%), urine flow (UV; 57%), and urinary sodium excretion
      (UNaV; 54%), accompanied by increased mean arterial pressure (17%) and heart rate
      (17%). These results were not obtained when Bic was injected outside the PVN or
      when vehicle (0.9% saline) was injected into the PVN. Bilateral renal denervation
      (5-7 days before the experiments) significantly reduced the renal
      vasoconstriction, attenuated the antidiuresis, and abolished the antinatriuresis
      evoked by PVN stimulation. On the other hand, both the antidiuresis and
      antinatriuresis evoked by PVN stimulation were undiminished after treatment with
      either of two vasopressin receptor antagonists ([beta-mercapto-beta,beta
      cyclopentamethylenepropionyl1,O-Et-Tyr2, Val4,Arg8]vasopressin, a vasopressin V1
      receptor antagonist, or [adamantaneacetyl1,O-Et-D-Tyr2,Val4,aminobutyryl6,Arg8,
      9]-vasopressin, a V2 receptor antagonist). In renal-denervated rats treated with
      the same V2 receptor antagonist, PVN stimulation produced highly variable
      increases in both UV and UNaV, which overall were not statistically different
      than zero. We conclude that the activation of neurons in PVN evokes 1) renal
      vasoconstriction accompanied by antinatriuresis, both of which are attributable
      to the renal nerves, and 2) decreased water excretion, which is mediated by the
      renal nerves and vasopressin V2 receptors.

PMID- 9756565
TI  - Role of small intestine in caloric compensations to oil premeals in rats.
AB  - We postulated that dose-responsive satiety after oil premeals varies with the
      number of gut sensors stimulated by lipolytic products along intestine. These
      experiments in fasted rats on satiety after oil premeals were performed to 1)
      determine whether satiety was induced by lipolytic products but not
      triglycerides; 2) confirm that oil empties from the stomach at rates that vary
      with oil loads; 3) ascertain that increasing rates of oil entry into duodenum
      extend the length of gut contacted by lipolytic products; and 4) judge whether
      length of gut contacted correlated with dose-responsive satieties to dietary
      oils. 5) Using specific antagonists, we attempted to define how satiety was
      signalled by gut sensors. Timing and degrees of satiety did not correlate with
      timing and extent of gastric distensions but, rather, with the timing and extent
      of spread of lipolytic products along small bowel. Satiety after the highest
      premeal load of oil was blocked by Pluronic L-81, an inhibitor of intestinal
      secretion of apolipoprotein A-IV, but was unaffected by MK-329 (a specific
      antagonist of cholecystokinin) or by capsaicin blockade of chemosensory nerves.

PMID- 9756567
TI  - Evidence for increased cardiac compliance during exposure to simulated
      microgravity.
AB  - We measured hemodynamic responses during 4 days of head-down tilt (HDT) and
      during graded lower body negative pressure (LBNP) in invasively instrumented
      rhesus monkeys to test the hypotheses that exposure to simulated microgravity
      increases cardiac compliance and that decreased stroke volume, cardiac output,
      and orthostatic tolerance are associated with reduced left ventricular peak
      dP/dt. Six monkeys underwent two 4-day (96 h) experimental conditions separated
      by 9 days of ambulatory activities in a crossover counterbalance design: 1)
      continuous exposure to 10 degrees HDT and 2) approximately 12-14 h per day of 80
      degrees head-up tilt and 10-12 h supine (control condition). Each animal
      underwent measurements of central venous pressure (CVP), left ventricular and
      aortic pressures, stroke volume, esophageal pressure (EsP), plasma volume, alpha1
      and beta1-adrenergic responsiveness, and tolerance to LBNP. HDT induced a
      hypovolemic and hypoadrenergic state with reduced LBNP tolerance compared with
      the control condition. Decreased LBNP tolerance with HDT was associated with
      reduced stroke volume, cardiac output, and peak dP/dt. Compared with the control
      condition, a 34% reduction in CVP (P = 0.010) and no change in left ventricular
      end-diastolic area during HDT was associated with increased ventricular
      compliance (P = 0.0053). Increased cardiac compliance could not be explained by
      reduced intrathoracic pressure since EsP was unaltered by HDT. Our data provide
      the first direct evidence that increased cardiac compliance was associated with
      headward fluid shifts similar to those induced by exposure to spaceflight and
      that reduced orthostatic tolerance was associated with lower cardiac
      contractility.

PMID- 9756568
TI  - Cytokine-induced fever in obese (fa/fa) and lean (Fa/Fa) Zucker rats.
AB  - In earlier work, we reported that genetically obese (fa/fa) Zucker rats exhibited
      significantly greater anorexia than did lean (Fa/Fa) Zucker rats to
      intracerebroventricular infusion of interleukin (IL)-1beta. Here, we investigated
      the fever response of obese (fa/fa) and lean (Fa/Fa) Zucker rats to
      intracerebroventricular microinfusion of IL-1beta as well as to the following
      other cytokines: IL-2, IL-6, and tumor necrosis factor-alpha (TNF-alpha). Core
      body temperature was monitored by a radiotelemetry system in freely moving rats.
      The results show that 1) both IL-1beta and IL-6 induce fevers in obese and lean
      rats; 2) IL-1beta induces a significantly higher fever response in obese rats
      than it does in lean rats; 3) IL-6 induces a significantly higher fever response
      in lean rats than it does in obese rats; 4) IL-2 induces a moderate fever
      response in lean but not obese rats; 5) TNF-alpha induces a similar fever
      response in obese and lean rats; and 6) the fevers induced by each effective
      cytokine have different time courses. Thus obese (fa/fa) and lean (Fa/Fa) Zucker
      rats show differential responsiveness to the intracerebroventricular
      microinfusion of various classes of cytokines. This suggests that genetic obesity
      in the fa/fa Zucker rat is associated with differential cytokine action on
      thermoregulatory mechanisms.

PMID- 9756569
TI  - Evidence for induction of a phosphate appetite in juvenile rats.
AB  - This study examined whether dietary phosphate (Pi) restriction stimulates an
      appetite for Pi in the juvenile rat, which normally has a high metabolic Pi
      demand for growth. Juvenile Wistar rats were placed in individual cages with
      unrestricted access to tap water and a low (LPD, 0.02% Pi) or normal Pi diet
      (NPD, 0.6% Pi) for 7 days. On day 8, both groups of rats were given unlimited
      access to a solution of 0.3 M potassium phosphate water (PiH2O) for 8 additional
      days. Rats fed LPD consumed 70-100% more PiH2O then those rats fed NPD (P <
      0.001). The increase in PiH2O intake resulted in a marked rise in the growth rate
      of rats fed LPD during days 8-15. A similar Pi intake was inducible after only 2
      days of LPD and was associated with significant reductions in both plasma and
      cerebrospinal fluid (CSF) Pi levels; these levels remained low throughout Pi
      restriction, despite a significant PiH2O intake. Furthermore, the renal
      adaptation to enhance Pi reabsorption (TmPi) during Pi deprivation remained
      elevated despite enhanced PiH2O intake. Replenishment with a high-Pi diet rapidly
      quenched the PiH2O appetite and was associated with restoration of both plasma
      and CSF Pi levels. These findings suggest that an appetite for Pi can be induced
      in juvenile rats, perhaps through lowered plasma and CSF Pi levels. This
      behavioral response may serve as an additional mechanism to maintain an adequate
      supply of Pi necessary for growth and development of the animal.

PMID- 9756571
TI  - Gestational obesity accentuates obesity in obesity-prone progeny.
AB  - Maternal obesity and genetic background can affect the development of obesity and
      diabetes in offspring. Here we used selected strains of rats resistant (DR) vs.
      susceptible to development of diet-induced obesity (DIO) on high-energy (HE)
      diets to assess this issue. DR and DIO dams were fed either Chow or HE diet for 4
      wk. DIO HE diet-fed dams and additional DR rats fed a palatable liquid diet
      (Ensure) became more obese and hyperinsulinemic than the other groups. During
      lactation, all dams were fed their respective diets, and offspring were fed Chow
      from weaning to 16 wk of age. All offspring of DIO dams gained more weight and
      had heavier retroperitoneal fat pads and higher leptin levels than DR progeny,
      but offspring of the more obese DIO HE dams had heavier fat pads and higher
      glucose levels than DIO Chow offspring. After 4 wk on HE diet, all DIO offspring
      gained more weight and had heavier total adipose depots and higher insulin and
      leptin levels than DR offspring. Offspring of DIO HE dams also gained more weight
      and had heavier fat depots and higher leptin levels than DIO Chow offspring.
      Therefore maternal obesity and hyperinsulinemia were associated with increased
      obesity in those offspring already genetically predisposed to become obese.

PMID- 9756570
TI  - Spinal and peripheral mechanisms contributing to hyperactive voiding in
      spontaneously hypertensive rats.
AB  - The influence of noradrenergic mechanisms involved in micturition in
      spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats was
      investigated using continuous cystometry in in vivo and in vitro studies on
      isolated bladder and urethral tissues. Compared with WKY rats, SHR had a
      significantly lower bladder capacity (SHR: 0.7 +/- 0. 05 ml; WKY rats: 1.3 +/-
      0.06 ml; P < 0.001), micturition volume (SHR: 0.4 +/- 0.04 ml, WKY rats: 1.2 +/-
      0.05 ml; P < 0.001), and an increased amplitude of nonvoiding (unstable) bladder
      contractions. The effects of intrathecal and intra-arterial doxazosin on
      cystometric parameters were more pronounced in SHR than in WKY rats. There was a
      marked reduction in nonvoiding contractions after intrathecal (but not intra
      arterial) doxazosin in SHR. Norepinephrine (0.1 microM-1 mM) failed to evoke
      contractions in bladder strips from WKY rats, in contrast to a weak contractile
      response in SHR. The response to electrical field stimulation was significantly
      less in bladder strips from SHR than from WKY rats. In WKY rats, norepinephrine
      produced concentration-dependent inhibition (87 +/- 5%, n = 6) of nerve-evoked
      bladder contractions. Almost no inhibition (11 +/- 8%, n = 6) was found in SHR.
      Alterations in bladder function of SHR appear to be associated with changes in
      the noradrenergic control of the micturition reflex, in addition to an increased
      smooth muscle and decreased neuronal responsiveness to norepinephrine. The marked
      reduction in nonvoiding contractions after intrathecal doxazosin suggests that
      the bladder hyperactivity in SHR has at least part of its origin in supraspinal
      and/or spinal structures.

PMID- 9756572
TI  - Pregnancy-induced changes in rabbit medial collateral ligament vasoregulation.
AB  - The ligaments of weight-bearing joints are known to become mechanically inferior
      during pregnancy, and it has been postulated that this may be due to changes in
      tissue perfusion. Calcitonin gene-related peptide (CGRP) and epinephrine exert a
      tonic influence on the vasculature of the medial collateral ligament (MCL), and
      the present study examined whether these vasoactive influences were altered by
      pregnancy. Ligament perfusion experiments were performed on primigravid New
      Zealand White rabbits with the use of laser Doppler perfusion imaging. In
      pregnant animals (day 29), MCL basal perfusion fell significantly compared with
      control; however, values returned to normal 5 days postpartum. In normal joints,
      topical application of CGRP resulted in a dose-dependent increase in MCL
      perfusion, whereas epinephrine administration caused a dose-dependent fall in
      blood flow. During pregnancy, the vasodilator effect of CGRP was completely
      abolished, whereas adrenergic vasoconstriction was greater than normal. Both
      responses returned postpartum. Pregnancy in the rabbit produces hypoemia in the
      MCL, and this phenomenon may be effected by a tempering of CGRP dilator responses
      and an augmentation of alpha-adrenoceptor-mediated vasoconstriction.

PMID- 9756573
TI  - AHA journals lead with definitive new online site.

PMID- 9756574
TI  - Changing practice and costs of carotid endarterectomy in Toronto, Canada.
AB  - BACKGROUND AND PURPOSE: During our annual audits of carotid endarterectomy (CEA)
      in Toronto metropolitan hospitals, we have been aware of major changes in the
      practice of this operation in recent years. To evaluate the effect of changing
      practice on costs of carotid endarterectomy, we have therefore compared the
      effects of changes in length of stay, complication rates, and other variables on
      cost during the last 3 years for which we have complete data. METHODS: We
      evaluated 757 consecutive patients, of whom 600 had CEA procedures in 3 teaching
      hospitals, and 190 procedures in 2 community hospitals in metropolitan Toronto.
      We estimated costs using a specially designed computer program, Transitional
      System Incorporated, including surgical complications, in patients admitted
      between January 1994 and December 1996. RESULTS: There was a significant decrease
      in length of stay in both groups of hospitals, mainly due to preoperative
      outpatient evaluation but also due to lower complication rates, which probably
      reflect an increase in asymptomatic surgery in both hospital groups. Costs fell
      from approximately $8000 per procedure to $5000 in asymptomatic patients and from
      approximately $10,000 to $7000 in symptomatic patients (Can $). CONCLUSIONS:
      Major changes in the management of patients undergoing CEA have resulted in a
      significant decrease in both length of hospital stay and utilization of
      postoperative intensive care. At the same time, complication rates have
      significantly fallen, although our mortality and morbidity figures remain
      slightly higher than those from published multicenter trials. Future changes in
      surgical practice in Canada, including noninvasive carotid imaging, should
      produce even lower costs within the next few years.

PMID- 9756575
TI  - Recurrent carotid stenosis : results of the asymptomatic carotid atherosclerosis
      study.
AB  - BACKGROUND AND PURPOSE: We sought to determine the incidence of recurrent carotid
      stenosis in patients in the Asymptomatic Carotid Atherosclerosis Study (ACAS) who
      had undergone carotid endarterectomy and were prospectively followed with Doppler
      ultrasound for up to 5 years. METHODS: The ACAS database was interrogated to
      determine the rate of recurrent carotid stenosis (>/=60%) based up angiogram
      validated Doppler data, with a 90% and a 95% positive predictive value, as well
      as information concerning the technologists' interpretation of percent stenosis.
      These 3 parameters are reported for each of 3 time intervals: within 3 months of
      operation (residual disease), between 3 and 18 months (early restenoses), and
      between 18 and 60 months (late restenosis). RESULTS: Of the 825 patients
      randomized to the surgical arm of the study, 720 actually underwent carotid
      endarterectomy, and 645 had complete ultrasound data. The aggregate incidence of
      residual and recurrent carotid stenosis for all time intervals ranged from 12.7%
      to 20.4%, depending on the positive predictive value confidence level desired.
      Residual disease occurred in 4.1% to 6.5%; true, early restenosis was found in
      7.6% to 11.4%; and late restenosis occurred in 1.9% to 4.9%. None of the
      traditional risk factors showed a statistically significant effect on recurrent
      stenosis. The use of patch angioplasty closure reduced overall risk of restenosis
      from 21.2% to 7.1%, from 16.7% to 4.6%, and from 27.4% to 8.2%, depending on the
      PPV confidence level desired (P<0.001). Of the 136 patients judged to have
      recurrent stenosis, only 8 (5.9%) underwent reoperation (only 1 for symptoms).
      There was no correlation between late stroke and recurrent stenosis. CONCLUSIONS:
      Carotid endarterectomy is a durable procedure with a low rate of true restenosis,
      particularly when patch angioplasty is used to close the arteriotomy.

PMID- 9756576
TI  - Three-dimensional ultrasound study of carotid arteries before and after
      endarterectomy; analysis of stenotic lesions and surgical impact on the vessel.
AB  - BACKGROUND AND PURPOSE: It has been proved that symptomatic patients with severe
      carotid stenosis benefit from endarterectomy. Currently used methods for
      quantitation of the severity of carotid stenosis have limitations, and the impact
      of endarterectomy on the operated region of carotid artery remains unknown. The
      purpose of this study was to examine the accuracy of a 3-D ultrasound system for
      quantitation of stenotic lesions and to evaluate changes in regional vessel
      volume and cross-sectional area after carotid endarterectomy. METHODS: We studied
      14 patients with both carotid angiography and 3-D ultrasound. Of 13 patients who
      underwent surgery, 12 were reexamined with 3-D ultrasound after surgery. The
      length and volume of 20 randomly selected plaques were measured from 3-D data
      sets. The severity of stenosis was quantified by 3-D ultrasound using both a
      diameter method and an area method on cross-sectional views at the most stenotic
      site; the results were then compared with those from carotid angiography. The
      segmental vessel volume and average cross-sectional area of the operated artery
      both before and after endarterectomy were measured from 3-D ultrasound data.
      RESULTS: Good correlation was obtained between 3-D ultrasound and carotid
      angiography in quantitative analysis of carotid stenosis (SEE=12.4%, r=0.76, and
      mean difference=7.0+/-12.3% with the diameter method; SEE=10.5%, r=0.82, and mean
      difference=1.8+/-10.5% with the area method by 3-D ultrasound). 3-D ultrasound
      had excellent reproducibility and small intraobserver and interobserver
      variability in plaque length and volume measurements. No significant changes in
      segmental vessel volume and average cross-sectional area of the operated artery
      were observed after surgery in patients with suture closure. However, a
      significant increase in segmental vessel volume was obtained in patients with
      polyfluorethylene patches applied to the surgical opening of the artery.
      CONCLUSIONS: 3-D ultrasound can be used for both qualitative and quantitative
      analysis of plaques in the carotid artery and to detect and quantify significant
      carotid stenosis. Its volumetric potential has important clinical implications in
      serial follow-up studies for observing the progression or regression of stenotic
      lesions and for evaluating the outcome of interventional procedures such as
      endarterectomy or stent placement.

PMID- 9756577
TI  - Comparison of near-infrared spectroscopy and somatosensory evoked potentials for
      the detection of cerebral ischemia during carotid endarterectomy.
AB  - BACKGROUND AND PURPOSE: We sought to assess the clinical value of regional
      cerebral saturation (rSO2) obtained by means of the cerebral oximeter INVOS 3100A
      (Somanetics) in comparison to monitoring of somatosensory evoked potentials (SEP)
      for the reliable detection of severe cerebral ischemia requiring shunt placement
      in the individual patient undergoing carotid surgery under general anesthesia.
      METHODS: In 317 patients undergoing reconstructive surgery on the internal
      carotid artery, simultaneous recordings of SEP and rSO2 were obtained throughout
      the operation. RESULTS: All 287 patients with preserved cortical SEP remained
      neurologically intact. Shunt placement was performed in 27 patients (9%) after
      flattening of cortical SEP during cross-clamping of the internal carotid artery.
      A stable rSO2 value just before cross-clamping and the lowest value after cross
      clamping were registered, and the decrease was calculated. A statistically
      significant (P<0.01) decrease of rSO2 after cross-clamping could be found in
      patients without (64.9+/-8.3% to 60.9+/-9.9%) as well as in patients with
      consecutive loss of cortical SEP (65.8+/-9.1% to 56.1+/-13.4%). The difference of
      the decrease of rSO2 in both groups was highly significant (6.9+/-9.0% versus
      15.6+/-14.0%; P<0.001). However, substantial interindividual variability of rSO2
      and derived change of rSO2 did not allow the definition of a threshold value
      indicating need of shunt placement. CONCLUSIONS: The reliability of SEP for the
      detection of clamp-related hypoperfusion has been reaffirmed. As long as rSO2
      threshold values indicating critical cerebral ischemia are not defined,
      therapeutic interventions based on monitoring with the cerebral oximeter INVOS
      3100A are not justified.

PMID- 9756578
TI  - Predicting the effect of carotid artery occlusion during carotid endarterectomy:
      comparing transcranial doppler measurements and cerebral angiography.
AB  - BACKGROUND AND PURPOSE: We correlated the mean transcranial Doppler blood flow
      velocity (FVm) during carotid endarterectomy with the functional collateral
      pathway(s) documented by angiography. METHODS: Three patient groups were
      established: group 1 was dependent on the anterior communicating artery, group 2
      on the anterior communicating artery and ipsilateral posterior communicating
      artery, and group 3 on the ipsilateral posterior communicating artery. Continuous
      middle cerebral artery FVm and electroencephalographic monitoring were performed
      in 45 patients during carotid endarterectomy. RESULTS: Clamped FVm was lowest in
      group 3 at 17+/-9 cm/s versus 36+/-16 and 33+/-11 cm/s for groups 1 and 2
      (P<0.01). FVm values in groups 1 and 2 were similar. There was significant
      cerebral arterial vasodilation in group 3 patients on the basis of a pulsatility
      index of 0.38+/-0.15. The maximum FVm after clamp release was similar among the 3
      groups. Normalized blood flow velocity 1 minute before release of the clamp was
      increased from the minimum flow velocity after clamping only in group 1 and 2
      patients. CONCLUSIONS: The ipsilateral posterior communicating artery is a minor
      collateral pathway during acute carotid occlusion that contributes little to the
      collateral flow if there is a functional anterior communicating artery.
      Collateral flow through the middle cerebral artery is not recruited during
      occlusion in group 3 patients. The reperfusion FVm transient is independent of
      the primary collateral pathway. Documentation of functional collateral pathways
      on the basis of Doppler or angiographic examination may be advantageous in future
      studies since it can provide the basis for comparison among studies.

PMID- 9756579
TI  - Paraoxonase PON1 polymorphism leu-Met54 is associated with carotid
      atherosclerosis: results of the Austrian Stroke Prevention Study.
AB  - BACKGROUND AND PURPOSE: Genetic polymorphism at the paraoxonase locus is
      associated with serum concentration and activity of paraoxonase and with
      increased risk for coronary heart disease. Two frequent polymorphisms present at
      the paraoxonase gene are the methionine (M allele) leucine (L allele) interchange
      at position 54 and the arginine (B allele) glutamine (A allele) interchange at
      position 191. This is the first study to determine the effect of these
      polymorphisms on carotid atherosclerosis. METHODS: The paraoxonase genotypes at
      positions 54 and 191 of 316 randomly selected individuals aged 44 to 75 years
      were determined by polymerase chain reaction-based restriction enzyme digestion.
      Carotid atherosclerosis was assessed by color-coded Duplex scanning and was
      graded on a 5-point scale ranging from 0 (normal) to 5 (complete luminal
      obstruction). RESULTS: The LL, LM, and MM genotypes at position 54 were noted in
      137 (43.4%), 132 (41.8%), and 47 (14.9%) subjects; the AA, AB, and BB genotypes
      at position 191 occurred in 172 (54.4%), 124 (39.2%), and 20 (6.3%) individuals.
      The LL genotype was significantly associated with the presence and severity of
      carotid disease (P=0.022), whereas the 191 polymorphism had no effect. Logistic
      regression analysis with age and sex forced into the model demonstrated plasma
      fibrinogen (odds ratio [OR], 1.005 per mg/dL), LDL cholesterol (OR, 1.01 per
      mg/dL), cardiac disease (OR, 1.75), and the paraoxonase LL genotype to be
      significant predictors of carotid atherosclerosis. The ORs for the associations
      with age and sex were 1.09 (P=0.0003) and 1.66 (P=0.052) per year. CONCLUSIONS:
      These data suggest that the paraoxonase LL genotype may represent a genetic risk
      factor for carotid atherosclerosis.

PMID- 9756580
TI  - Physical activity and stroke incidence: the Harvard Alumni Health Study.
AB  - BACKGROUND AND PURPOSE: Physiologically, it appears plausible for physical
      activity to decrease stroke risk; however, epidemiological studies have produced
      mixed findings. Furthermore, few studies have examined specific kinds and
      intensities of activities. The purpose of this study was to examine the
      association between physical activity, including its various components (walking,
      climbing stairs, participation in sports and recreational activities), and stroke
      risk. METHODS: This was a prospective cohort study of 11 130 Harvard University
      alumni (mean age, 58 years) without cardiovascular disease and cancer at
      baseline. Men reported their walking, stair climbing, and participation in sports
      or recreation on baseline questionnaires in 1977. Stroke occurrence was assessed
      with another questionnaire in 1988. Death certificates were obtained for
      decedents through 1990 to determine strokes not previously reported (total
      strokes=378). We used Cox proportional hazards regression to estimate the
      relative risks and 95% CIs for stroke occurrence associated with physical
      activity. RESULTS: After adjustment for age, smoking, alcohol intake, and early
      parental death, the relative risks of stroke associated with <1000, 1000 to 1999,
      2000 to 2999, 3000 to 3999, and >/=4000 kcal/wk of energy expenditure at baseline
      were 1.00 (referent), 0.76 (95% CI, 0.59 to 0.98), 0.54 (0.38 to 0. 76), 0.78
      (0.53 to 1.15), and 0.82 (0.58 to 1.14), respectively; P=0. 05 for linear trend.
      Walking >/=20 km/wk was associated with significantly lower risk, independent of
      other physical activity components. Climbing stairs and activities of at least
      moderate intensity (>/=4.5 METs, or multiples of resting metabolic rate) each
      showed U-shaped relations to stroke risk, with the risk being significantly lower
      at the nadir of the curve. Light intensity activities (<4.5 METs), however, were
      unrelated to stroke risk. CONCLUSIONS: Physical activity is associated with
      decreased stroke risk in men. A decreased risk was observed at energy
      expenditures of 1000 to 1999 kcal/wk, with further risk decrement seen at 2000 to
      2999 kcal/wk but not beyond. Confirmation of the U-shaped relation observed in
      these data requires similar observations in other populations.

PMID- 9756581
TI  - A randomized, controlled pilot study of a home-based exercise program for
      individuals with mild and moderate stroke.
AB  - BACKGROUND AND PURPOSE: Many stroke survivors have minimal to moderate
      neurological deficits but are physically deconditioned and have a high prevalence
      of cardiovascular problems; all of these are potentially modifiable with
      exercise. The purposes of this randomized, controlled pilot study were (1) to
      develop a home-based balance, strength, and endurance program; (2) to evaluate
      the ability to recruit and retain stroke subjects; and (3) to assess the effects
      of the interventions used. METHODS: Twenty minimally and moderately impaired
      stroke patients who had completed inpatient rehabilitation and who were 30 to 90
      days after stroke onset were randomized to a control group or to an experimental
      group that received a therapist-supervised, 8-week, 3-times-per-week, home-based
      exercise program. The control group received usual care as prescribed by the
      patients' physicians. Baseline and postintervention assessments included the Fugl
      Meyer Motor Assessment, the Barthel Index of Activities of Daily Living (ADL),
      the Lawton Scale of Instrumental ADL, and the Medical Outcomes Study-36 Health
      Status Measurement. Functional assessments of balance and gait included a 10-m
      walk, 6-Minute Walk, and the Berg Balance Scale. Upper extremity function was
      evaluated by the Jebsen Test of Hand Function. RESULTS: Of 22 patients who met
      study criteria, 20 completed the study and 2 refused to participate. The
      experimental group tended to improve more than the control group in motor
      function (Fugl-Meyer Upper Extremity: mean change in score, 8. 4 versus 2.2; Fugl
      Meyer Lower Extremity: 4.7 versus -0.9; gait velocity: median change, 0.25 versus
      .09 m/s; 6-Minute Walk: 195 versus 114 ft; Berg Balance Score: 7.8 versus 5; and
      Medical Outcomes Study-36 Health Status Measurement of Physical Function: 15. 5
      versus 9). There were no trends in differences in change scores by the Jebsen
      Test of Hand Function, Barthel Index, and Lawton Instrumental ADL Scale.
      CONCLUSIONS: This study demonstrated that a randomized, controlled clinical trial
      of a poststroke exercise program is feasible. Measures of neurological
      impairments and lower extremity function showed the most benefit. Effects of the
      intervention on upper extremity dexterity and functional health status were
      equivocal. The lasting effects of the intervention were not assessed.

PMID- 9756582
TI  - The geographic variation in stroke incidence in two areas of the southeastern
      stroke belt: the Anderson and Pee Dee Stroke Study.
AB  - BACKGROUND AND PURPOSE: South Carolina and the southeastern United States have
      maintained the highest stroke mortality in the country. The Anderson and Pee Dee
      Stroke Study is an assessment of cerebrovascular disease incidence in 2
      geographically defined communities in the stroke belt. METHODS: Strokes were
      identified in the Anderson and Pee Dee areas of South Carolina. All hospitalized
      and out-of-hospital deaths occurring during 1990 among the residents of these 2
      areas were included. Strokes were classified by an independent panel of
      neurologists using a standard protocol that included specific criteria for stroke
      and subtypes. RESULTS: The overall age-adjusted stroke incidence rates (per 100
      000 population) were significantly higher in the Pee Dee population (293.1)
      compared with Anderson (211.2). The geographic differences were more dramatic in
      the younger age groups of 35 to 64 years. Likewise, incidence rates for blacks
      were nearly twice the rates for whites. The rates in the Pee Dee were higher than
      the rates from other studies in the United States and other parts of the world.
      Although the stroke subtypes did not vary between the 2 regions, race-sex
      differences were identified. CONCLUSIONS: High stroke incidence and disease rates
      persist for all 4 race-sex groups in the Southeast and reflect similar risks as
      mortality rates. However, geographic variability in stroke rates suggests that
      the pattern of disease in the region is not so much a "belt" of increased stroke
      in contiguous areas but rather more a "necklace" of different levels of risk.
      These results should be useful in the identification of factors associated with
      this geographic enigma.

PMID- 9756583
TI  - North Carolina stroke prevention and treatment facilities survey: rtPA therapy
      for acute stroke.
AB  - BACKGROUND AND PURPOSE: North Carolina is situated in the "stroke belt" region of
      the United States, an area of the country with a particularly high incidence of
      cerebrovascular disease. The North Carolina Stroke Prevention and Treatment
      Facilities Survey was carried out to determine the availabilities of a variety of
      stroke prevention and treatment services throughout the state. The purpose of the
      present study was to determine how widely recombinant tissue-type plasminogen
      activator (rtPA) has been adopted for the treatment of patients with acute
      ischemic stroke and to determine the characteristics of the medical facilities in
      the state offering this therapy. METHODS: A single-page survey was mailed to the
      medical center directors of each inpatient medical facility in North Carolina.
      Data collected included questions related to the availability of selected basic
      and advanced diagnostic tests and procedures, stroke prevention and treatment
      programs and services (community stroke awareness program, acute stroke
      identification program, acute stroke team, stroke rtPA protocol, stroke care map,
      neurologist), and facilities (Stroke Acute Care Unit or equivalent). RESULTS:
      Responses were obtained from all 125 inpatient medical facilities in North
      Carolina. rtPA stroke protocols were adopted in 54 facilities located in 46 of
      the state's 100 counties. Seventy-four percent of the state's population resides
      in counties with hospitals providing rtPA treatment. Compared with facilities not
      offering rtPA, those with rtPA protocols more commonly sponsored stroke community
      awareness programs (41% versus 17%, P=0.003) and more frequently had an organized
      stroke team (31% versus 8%, P=0. 001), used stroke care maps (56% versus 17%,
      P<0.001), had rapid stroke identification programs (33% versus 6%, P<0.001), or
      had a Stroke Acute Care Unit or its equivalent (33% versus 7%, P<0.001).
      Neurologists were available in 78% of the facilities offering rtPA compared with
      38% in facilities without rtPA protocols (P<0.001). CONCLUSIONS: These data show
      that this new therapy for ischemic stroke is potentially available to a high
      proportion of the state's citizens based on their county of residence. However,
      other services that may improve outcomes and reduce stroke-related costs (eg,
      stroke teams, stroke units, care maps) are not being widely used, even in centers
      providing treatment with rtPA. The simple methodology used in this study is
      potentially applicable in other states and permits targeting of selected centers
      for development of stroke treatment capabilities.

PMID- 9756584
TI  - Dichotomized efficacy end points and global end-point analysis applied to the
      ECASS intention-to-treat data set: post hoc analysis of ECASS I.
AB  - BACKGROUND AND PURPOSE: It is not yet known which end points are the most
      suitable for evaluation of the effects of acute stroke intervention. The European
      Cooperative Acute Stroke Study (ECASS) I study used 2 primary end points. The
      study was powered to detect a 15% improvement of the median of each primary end
      point. The study failed to show this effect and was negative in the intention-to
      treat analysis. The National Institute of Neurological Disorders and Stroke
      (NINDS) study used 4 dichotomized end points and applied a global end-point
      analysis. This study was positive and led to FDA approval of thrombolytic therapy
      for acute ischemic stroke. This study was undertaken to answer the question of
      whether a different statistical design may have shown a positive results of the
      ECASS I trial. METHODS: We performed a retrospective analysis of the ECASS I
      intention-to-treat data set (615 randomized and treated patients, rtPA treatment
      versus placebo) and post hoc application of the NINDS trial statistical
      methodology (global end-point analysis). The scores of the modified Rankin Scale
      (mRS), Barthel Index (BI), and the National Institutes of Health Stroke Scale
      (NIHSS) were dichotomized according to the criteria used in the NINDS trial.
      Favorable outcome was defined as a score of 0 or 1 on mRS, a score of 95 or 100
      on BI, and a score of 0 or 1 on NIHSS. RESULTS: The number of patients reaching
      favorable outcome were higher in all 3 end points in the rtPA-treated group. The
      effect sizes were 8% for mRS, 6% for BI, and 14% for NIHSS, respectively. The
      differences are statistically significant for the mRS (P=0.044; odds ratio [OR],
      1. 4; 95% confidence interval [CI], 1.0 to 2.0) and the NIHSS (P=0.001; OR, 1.9;
      95% CI, 1.4 to 2.8), while for the BI significance was missed (P=0.102; OR, 1.3;
      95% CI, 0.9 to 1.8). The global end-point statistics, however, shows a
      significant increase (P=0.008; OR, 1.5; 95% CI, 1.1 to 2.0) of favorable outcome
      in the rtPA-treated patient group. CONCLUSIONS: Using the global end-point
      analysis, ECASS is positive in the intention-to-treat analysis. This may indicate
      that the time window for thrombolysis may be as long as 6 hours. Looking at the 3
      dichotomized end points, the effect sizes for 2 end points, mRS and BI, are
      smaller in the ECASS 6-hour intention-to-treat population compared with the NINDS
      trial, whereas the effect size for the NIHSS is larger. While in the NINDS trial
      all 3 end points reveal statistically significant results, in ECASS only 2 of the
      3 corresponding end points, mRS and NIHSS, were statistically significant. This
      finding underlines an important difference of a global end-point approach: it may
      show a positive overall result although one of the end points is not positive.

PMID- 9756586
TI  - The CAMCOG: a useful screening instrument for dementia in stroke patients.
AB  - BACKGROUND AND PURPOSE: Most mental screening tests focus on the detection of
      cognitive deficits compatible with Alzheimer's disease. Stroke patients who
      develop a dementia syndrome, however, constitute a more heterogeneous group with
      both cortical and subcortical disturbances. We assessed the diagnostic accuracy
      of the CAMCOG (the cognitive and self-contained part of the Cambridge Examination
      for Mental Disorders of the Elderly) and the Mini-Mental State Examination (MMSE)
      for dementia in patients with a recent stroke. METHODS: In patients aged 55 and
      older who were admitted in the Rotterdam Stroke Databank, cognitive functioning
      was assessed between 3 and 9 months after the most recent stroke. The "gold
      standard" diagnosis of dementia was compatible with the criteria of the
      Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised.
      The CAMCOG and MMSE scores were obtained independent of the diagnostic procedure.
      RESULTS: Of 300 consecutive patients, 71 (23.7%) were demented. Sixteen severely
      demented patients could not be tested and were excluded. The CAMCOG and MMSE
      scores were significantly related to dementia (both P<0.0001) in a logistic
      regression model. Receiver operating characteristic analysis showed that the
      CAMCOG was a more accurate screening instrument (area under the curve for CAMCOG,
      0.95; for MMSE, 0.90). Two other clinical variables independently improved the
      diagnostic accuracy of the MMSE and CAMCOG: patients with a left hemispheric
      lesion had a lower (odds ratio, 0.3; 95% confidence interval, 0.1 to 0.7), and
      patients with hemorrhagic stroke had a greater chance of being demented (odds
      ratio, 3; 95% confidence interval, 1 to 10). The effect of left hemispheric
      lesion as an independent diagnostic factor could not be explained by selection or
      its association with aphasia alone. CONCLUSIONS: The CAMCOG is a feasible
      instrument for use in patients with a recent transient ischemic attack or stroke.
      It is a more accurate screening tool for dementia than the MMSE, especially when
      type and site of stroke are taken into account.

PMID- 9756585
TI  - Selective intra-arterial fibrinolysis of acute central retinal artery occlusion.
AB  - BACKGROUND AND PURPOSE: Occlusion of the central retinal artery (CRAO) causes a
      sudden decrease of monocular vision. Because early restoration of blood flow may
      improve outcome, we attempted to treat CRAO with selective intra-arterial
      fibrinolysis. METHODS: Intra-arterial fibrinolysis was performed within 6 hours
      after symptom onset in 17 patients with thromboembolic CRAO. Symptoms were
      painless, acute and severe decrease of vision. Urokinase (100 000 to 900 000 IU)
      was given through a microcatheter into the ophthalmic artery over 10 to 90
      minutes. For comparison, the history and visual outcome of 15 control patients
      who did not receive fibrinolytics were evaluated. In both groups some of the
      patients underwent paracentesis and/or received carboanhydrase inhibitors.
      RESULTS: Patients who underwent fibrinolysis fared better than control patients
      (P=0.01). Three patients (17.6%) recovered completely after fibrinolysis and
      regained visual acuity of 20/20 (n=2) to 25/20 (n=1). Two additional patients
      (11.8%) showed a marked improvement to a visual acuity of 20/30. In 6 patients
      (35. 3%) vision improved slightly. They were able to count fingers, detect hand
      movements, or perceive light. In 6 patients (35.3%), fibrinolytic treatment was
      without effect. Among control patients, 1 patient (6.7%) showed partial, 4
      patients (26.7%) minimal, and 10 (66.7%) no improvement of vision. CONCLUSIONS: A
      complete or marked improvement of visual acuity was achieved in one third of
      intra-arterial fibrinolysis patients but in none of the control patients. Intra
      arterial fibrinolysis seems to have the potential to "lighten" the spontaneously
      poor outcome of CRAO.

PMID- 9756587
TI  - Incidence and determinants of poststroke dementia as defined by an informant
      interview method in a hospital-based stroke registry.
AB  - BACKGROUND AND PURPOSE: Inconsistent information about incidence and determinants
      of poststroke dementia might be related to patient attrition, partly because of
      nonapplicability of formal neuropsychological testing to a large proportion of
      patients registered in a definite setting. METHODS: Using a proxy-informant
      interview based on ICD-10 criteria, we determined dementia at stroke onset and 1
      year after stroke in the 339 patients who survived, were available for follow-up,
      and were not demented at stroke onset of 635 patients entered over a 1-year
      period in a stroke registry taken at 2 community hospitals in Florence, Italy.
      RESULTS: Of the 339 patients, 57 (16.8%) proved to have poststroke dementia.
      These patients were older, more frequently female, and more often (multivariate
      odds ratio, 2.35; 95% CI, 1.21 to 4.58) had atrial fibrillation than those
      without dementia. Aphasia and the clinical features expressing the severity of
      the stroke event in the acute phase predicted poststroke dementia. CONCLUSIONS:
      In a hospital-based nonselected series of stroke survivors, despite the use of a
      method with low sensitivity for defining dementia, our study confirms that
      dementia is a frequent sequela of stroke and is mainly predicted by stroke
      severity. Certain determinants could be controlled in the prestroke phase, thus
      reducing its risk.

PMID- 9756588
TI  - Association of stroke with dementia, cognitive impairment, and functional
      disability in the very old: a population-based study.
AB  - BACKGROUND AND PURPOSE: Stroke is a major cause of disability in the elderly and
      is also related to the development of dementia, which is another important source
      of disability in old age. The aim of the present study was to examine the
      potential impact of stroke on cognitive and functional status in a community
      based cohort of individuals aged 75 years and older. METHODS: The data were
      derived from a cross-sectional survey on aging and dementia that included all
      inhabitants of the Kungsholmen district in central Stockholm who were aged >/=75
      years. Cases of stroke were identified through the computerized inpatient
      register system that has been widely used to study stroke in Sweden. Dementia was
      defined according to the Diagnostic and Statistical Manual of Mental Disorders,
      Third Edition, Revised. Dementia onset was considered the appearance, according
      to an informant, of the first symptom. Cognitive impairment without dementia was
      defined as the presence of a Mini-Mental State Examination score of <24 and the
      absence of dementia. Functional disability was assessed according to Katz Index
      of independence in activities of daily living. RESULTS: The prevalence of stroke
      was 10. 0% in men and 8.0% in women. One third of stroke survivors were diagnosed
      as demented, which was 3 times higher than those without stroke: adjusted odds
      ratio (OR) was 3.6 (95% confidence interval, 2. 5 to 5.8). Stroke was also
      significantly related to cognitive impairment without dementia (adjusted OR, 2.4
      [95% confidence interval, 1.3 to 4.6]). The population-attributable risks of
      dementia and cognitive impairment in relation to stroke were 18.4% and 8.5%,
      respectively. Among the 49 stroke patients with dementia, 15 cases (30.6%) had
      missing information on dementia onset, 22 (44. 9%) had been reported by the
      informant to have dementia-related symptoms after or close to the occurrence of
      stroke, and 12 (24.5%) had symptoms before stroke occurrence. The prevalence
      rates of disability in activities of daily living were much higher among stroke
      patients than among stroke-free subjects, even after adjustment for age, sex,
      heart disease, hip fracture, and dementia: the corresponding adjusted ORs for
      bathing, dressing, toileting, transfer, and continence were 3.5 (2.4 to 5.3), 2.2
      (1.4 to 3.3), 3. 0 (2.0 to 4.5), 3.3 (1.9 to 5.7), and 2.1 (1.3 to 3.3),
      respectively. After dementia and hip fracture, stroke was the third largest
      contributor to disability in bathing, dressing, and transfer. Stroke was the
      second contributor to disability in toileting. CONCLUSIONS: Stroke is strongly
      associated with dementia, although it may relate to dementia in different ways:
      it can be the main cause or a precipitating factor of dementia, or they may share
      common etiological bases. Together with dementia and hip fracture, stroke is a
      major contributor to disability in most aspects of activities of daily living in
      very old people.

PMID- 9756589
TI  - Effects of acupuncture treatment on daily life activities and quality of life: a
      controlled, prospective, and randomized study of acute stroke patients.
AB  - BACKGROUND AND PURPOSE: A number of studies have indicated that acupuncture might
      improve the functional recovery of stroke patients. These studies vary in
      inclusion criteria, sample size, and evaluation methods. The present study was
      designed to investigate whether electroacupuncture treatment favorably affects
      stroke patients' ability to perform daily life activities, their health-related
      quality of life, and their use of health care and social services. METHODS: One
      hundred four consecutive patients >40 years of age admitted to hospital because
      of an acute stroke were randomized to 3 groups: deep, superficial, and no
      acupuncture treatment. The acupuncture treatment given by 4 physiotherapists
      started 4 to 10 days after randomization and was given twice a week for 10 weeks.
      All patients underwent conventional stroke rehabilitation as well. Two
      occupational therapists, blinded regarding the patients' allocation, evaluated
      the treatment effects. The assessments were performed 4 times during the first
      year after randomization by means of interviews and observations. RESULTS: There
      were no differences between the groups with reference to changes in the
      neurological score and the Barthel and Sunnaas activities of daily living index
      scores after 3 and 12 months. Regarding the Nottingham Health Profile, the no
      acupuncture group had somewhat fewer mobility problems. No differences in health
      care and social services were found between the groups. CONCLUSIONS: The present
      study does not give support to the previous studies, which indicates that
      acupuncture treatment may have a beneficial effect on acute stroke patients'
      ability to perform daily life activities, their health-related quality of life,
      and their use of health care and social services.

PMID- 9756590
TI  - Incidence of transient ischemic attack in Rochester, Minnesota, 1985-1989.
AB  - BACKGROUND AND PURPOSE: There is scant information available on the incidence of
      transient ischemic attack (TIA) in a defined population. This study defines
      incidence rates of first TIA and subtypes of TIA during 1985-1989 and compares
      the incidence to that obtained from a 1960-1972 cohort study. METHODS: Medical
      records of all residents of Rochester with potential diagnosis of TIA during 1985
      1989 were screened to determine whether the case met the criteria for TIA. All
      available data were used to determine the vascular distribution of the TIA.
      Average annual age- and sex-adjusted incidence rates were calculated for 1985
      1989, and results were compared with incidence rates determined in a Rochester
      based 1960-1972 cohort study. RESILTS: Two hundred two cases of first TIA or
      amaurosis fugax occurred among Rochester residents during 1985-1989. The age- and
      sex-adjusted incidence rate for any TIA was 68/100 000 population. Incidence of
      amaurosis fugax was 13/100 000; anterior circulation (cerebral) TIA, 38/100 000;
      and vertebrobasilar distribution TIA, 14/100 000. Rates were similar to those
      determined from a 1960-1972 cohort study. CONCLUSIONS: The incidence rate of TIA
      is 41% that of stroke incidence. TIA incidence in Rochester, Minn, is higher than
      has been previously reported for other sites throughout the world. Although
      comparison with prior time periods is difficult because of ascertainment issues,
      it appears that there has been no significant change in TIA incidence since the
      decade of the 1960s or earlier. This suggests that the most common mechanism for
      TIA (atherosclerosis) has not changed in prevalence, nor have risk factors
      leading to this mechanism.

PMID- 9756591
TI  - Three-year survival and recurrence after stroke in Malmo, Sweden: an analysis of
      stroke registry data.
AB  - BACKGROUND AND PURPOSE: Data from the Malmo Stroke Registry were analyzed to
      determine whether any change in survival or nonfatal stroke recurrence rates had
      occurred during the 4-year period from 1989 through 1992 and whether prognosis
      was related to area of residence. METHODS: The series comprised 2290 patients,
      1051 men and 1239 women, followed up for 3 years after their first stroke during
      the period 1989 through 1992. RESULTS: Of the series as a whole, 959(43.4%) died
      and 137(6%) suffered a second nonfatal stroke. Multivariate analysis showed age,
      type of stroke, severity of stroke, and the presence of diabetes mellitus or
      cardiac disease each to be an independent predictor of mortality, and the
      presence of diabetes, atrial fibrillation, and history of transient ischemic
      attacks each to be associated with increased risk of recurrence. Treatment for
      hypertension was associated with a protective effect. As compared to those with
      first stroke in 1989, those with first stroke in 1992 were characterized by a
      lower recurrence rate, which was reduced by 70% in the male subgroup (P=0.003)
      and by 80% in the female subgroup (P=0.006), the corresponding reduction in all
      cause mortality being 30% (P=0.007) and 10% (P=0.5, NS). Recurrence-free survival
      rates differed markedly between the 17 residential areas studied. CONCLUSIONS:
      The present study showed that survival rates after stroke have improved and
      recurrence rates have declined in this urban population. Further studies are
      needed to ascertain to what extent intraurban variation in the proportion of
      recurrence-free 3-year survivors is to be explained by differences in the
      severity of initial stroke and other prognostic markers, or in initial treatment
      and secondary preventive measures.

PMID- 9756592
TI  - Risk factors for early recurrence after ischemic stroke: the role of stroke
      syndrome and subtype.
AB  - BACKGROUND AND PURPOSE: Information regarding risk factors for early recurrence
      is limited. Our aim was to identify the clinical predictors of early recurrence
      after ischemic stroke. METHODS: We prospectively examined 297 patients (mean age,
      72.0+/-8.4 years) hospitalized with ischemic stroke to identify recurrent strokes
      occurring within 90 days of the index stroke. Survival free of recurrence was
      estimated using Kaplan-Meier analysis stratified by demographic variables;
      vascular risk factors; stroke syndrome, subtype, vascular territory, and
      severity; scores on the Barthel Index and Mini-Mental State Examination during
      hospitalization; blood pressure on admission; and selected laboratory data. We
      estimated the relative risk (RR) of early recurrence associated with those
      variables using proportional hazards analysis. RESULTS: We identified 22
      recurrent events in the first 90 days after the index stroke, resulting in an
      early stroke recurrence rate of 7.4%, and death occurred immediately after
      recurrence in 6 of the 22 patients. A major hemispheric stroke syndrome (RR=2.9;
      95% confidence interval [CI]=1.2 to 7.1), atherothrombotic stroke mechanism
      (RR=3.3; CI=1.3 to 8.3), and atrial fibrillation (RR=2.2; CI=0.8 to 6.1) were
      independent predictors of early recurrence, after adjustment for demographic
      variables. Conclusions-Early recurrence was frequent and resulted in increased
      mortality. Attention to the clinical features of the index stroke, including the
      presenting syndrome and the ischemic mechanism, and the recognition of atrial
      fibrillation may help in the selection of patients for the initiation of targeted
      interventions to prevent early recurrence and subsequent mortality.

PMID- 9756593
TI  - Microembolic signals and risk of early recurrence in patients with stroke or
      transient ischemic attack.
AB  - BACKGROUND AND PURPOSE: Asymptomatic microembolic signals (MES) can be
      demonstrated in patients with cerebral ischemia using transcranial Doppler (TCD)
      ultrasonographic monitoring of the middle cerebral artery. However, the clinical
      relevance of MES remains uncertain. The purpose of this study was to estimate the
      independent contribution of microembolism to the risk of early ischemic
      recurrence (EIR) in patients with stroke or transient ischemic attack (TIA) of
      presumed arterial origin. METHODS: We studied the incidence of EIR in 73
      consecutive patients with carotid stroke or TIA in whom TCD scanning of the
      symptomatic middle cerebral artery was performed within 7 days from the onset of
      symptoms. Patients with a potential cardiac source of embolism were excluded from
      the study. RESULTS: Eight patients had EIR during a mean+/-SD follow-up of 10+/-8
      days. The incidence of EIR was 4.3 per 100 patient-days in patients with MES and
      only 0.5 per 100 patient-days in patients without MES. The presence of MES was a
      significant predictor of EIR after adjustment for the presence of carotid
      stenosis or aortic arch atheroma, antiplatelet therapy during follow-up, and
      other potential confounding variables (relative risk, 8.7; 95% confidence
      interval, 2 to 38.2; P=0.0015). CONCLUSIONS: Microembolism is a significant
      independent predictor of EIR in patients with stroke or TIA of presumed arterial
      origin.

PMID- 9756594
TI  - A longitudinal prospective study of soluble adhesion molecules in acute stroke.
AB  - BACKGROUND AND PURPOSE: Activation of endothelial cells is a consequence of
      cerebral ischemia and leads to the expression of adhesion molecules such as
      intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1
      (VCAM-1), and E-selectin, which can be released into the blood. This study aimed
      to define the kinetics of soluble adhesion molecule serum levels after cerebral
      ischemia and their correlation with the extent of neurological deficits, clinical
      outcome, and infarct volume as measured on CT scans. Methods-Plasma levels of
      soluble (s) ICAM-1, sVCAM-1, and sE-selectin were repeatedly determined by ELISA
      in 38 patients during a period of 14 days after acute cerebral ischemia. RESULTS:
      Soluble adhesion molecule levels demonstrated considerable variability. Overall,
      concentrations revealed characteristic and significant changes after completed
      strokes but not after transient ischemic attacks. In patients with completed
      stroke (n=26) but not in patients with transient ischemic attacks (n=12), sICAM-1
      peaked within 24 hours (P=0.04), sVCAM-1 reached a maximum after 5 days (P=0.02),
      and sE-selectin levels decreased after 5 days (P=0.002). There was no clear-cut
      correlation of soluble adhesion molecule levels with infarct volume or clinical
      disability. The initial increase of sE-selectin levels was higher in more
      disabled patients (P=0.02). sICAM-1 levels were higher in patients with signs of
      infection (n=9; P=0.03). CONCLUSIONS: As a result of large interindividual
      variability influenced by ischemia-independent factors, soluble adhesion
      molecules are not reliable candidates as surrogate markers in acute cerebral
      ischemia. The characteristic profile of individual soluble adhesion molecules
      after completed stroke supports prior hypotheses of their involvement in the
      pathogenesis of acute cerebral ischemia, but this needs to be clarified in
      detail.

PMID- 9756595
TI  - Citicoline treatment for experimental intracerebral hemorrhage in mice.
AB  - BACKGROUND AND PURPOSE: Citicoline sodium (cytidine-5'-diphosphocholine) has been
      shown previously to reduce ischemic injury in focal central nervous system
      models. Intracerebral hemorrhage (ICH) appears to be associated with an area of
      edema and ischemic injury surrounding the hematoma that may be reduced by
      neuroprotective therapy. The present study was designed to test whether treatment
      with citicoline reduces ischemic injury and improves functional neurological
      outcome in an experimental model of ICH. METHODS: In 68 Swiss albino mice (26 to
      36 g), ICH was induced by collagenase injection into the caudate nucleus. Animals
      were randomized to receive either: citicoline 500 mg/kg or saline IP prior to
      collagenase and at 24 and 48 hours. Animals were rated on a 28-point neurological
      scale and sacrificed at 54 hours. The brains were sectioned, and the volume of
      hematoma, total lesion, and surrounding ischemic injury was determined. RESULTS:
      In terms of functional outcome, animals treated with citicoline had improved
      neurological outcome scores compared with placebo-treated animals: 10.4+/-2.0
      versus 12.1+/-2.4 (P<0.01). Regarding ischemic injury, although there was no
      difference in the underlying hematoma volumes, animals treated with citicoline
      had a smaller surrounding volume of ischemic injury than placebo-treated animals:
      citicoline, 13.8+/-5.8 mm3 (10.8+/-4.3% of hemisphere); placebo, 17.0+/-7.1 mm3
      (13.3+/-5. 1%) (P<0.05). CONCLUSIONS: In this animal model of ICH, treatment with
      citicoline significantly improved functional outcome and reduced the volume of
      ischemic injury surrounding the hematoma. This study supports a potential role
      for citicoline in clinical ICH treatment.

PMID- 9756596
TI  - YM872, a highly water-soluble AMPA receptor antagonist, preserves the hemodynamic
      penumbra and reduces brain injury after permanent focal ischemia in rats.
AB  - BACKGROUND AND PURPOSE: We recently described an image analysis technique based
      on the temporal correlation mapping (TCM) of injected contrast agents that can be
      used to distinguish the hemodynamic core and hemodynamic penumbra after focal
      ischemia. In this study we used this technique for the first time to investigate
      the effects of the water-soluble AMPA receptor antagonist YM872 in permanent
      focal ischemia. METHODS: Fischer 344 rats were subjected to permanent occlusion
      of the middle cerebral artery. Approximately 30 minutes after ischemia,
      functional CT images were collected with the use of a dynamic scanning protocol
      with bolus injections of nonionic contrast agent iohexol (1 mL/kg). TCM analysis
      defined the distributions of hemodynamic core and hemodynamic penumbra. Cerebral
      perfusion indices were calculated on the basis of the area under the first-pass
      transit curves. One hour after ischemia, animals were randomly treated with YM872
      (n=8, 20 mg/kg per hour over 4 hours) or normal saline (n=10). Twenty-four hours
      later, neurological deficits were evaluated, and conventional CT and
      triphenyltetrazolium chloride staining were used to define volumes of ischemic
      damage. RESULTS: At 24 hours after ischemia, hypodense lesions were visible on
      conventional CT scans that were highly correlated with triphenyltetrazolium
      chloride lesion volumes. YM872 improved neurological deficits and reduced volumes
      of ischemic damage in cortex (90+/-14 versus 170+/-16 mm3 in controls) but not
      striatum (57+/-14 versus 79+/-6 mm3 in controls). Comparison of early TCM images
      with conventional CT scans of ischemic injury showed that the hemodynamic core
      was always damaged in all rats. In controls, 54% of the tissue within the
      hemodynamic penumbra evolved into ischemic damage compared with 24% in YM872
      treated rats. Furthermore, the perfusion index corresponding to the ischemic
      damage threshold was significantly reduced by YM872 (28+/-2% versus 37+/-2% in
      controls). CONCLUSIONS: These results indicate that YM872 is a neuroprotective
      compound that ameliorates the deterioration of the hemodynamic penumbra after
      focal ischemia.

PMID- 9756597
TI  - Myosin light chain phosphorylation and contractile proteins in a canine two
      hemorrhage model of subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) impairs both contraction
      and relaxation response in cerebral arteries. We tested the hypothesis that
      cerebral vasospasm might be ATP-independent contraction, such as latch state, and
      protein synthesis might be substantially downregulated due to ATP consumption
      after long-lasting contraction. METHODS: Chronic cerebral vasospasm was induced
      in the canine 2-hemorrhage model of SAH. The normal and spastic basilar arteries
      were stabilized in Krebs-Henseleit solution, and contraction was induced by 30
      micromol/L prostaglandin F2alpha (PGF2alpha) in vitro and in vivo. Before and at
      15 minutes and 1 hour after the treatment with PGF2alpha, the levels of
      phosphorylated 20-kDa myosin light chain (MLC20) were measured. The time course
      of expression of contraction proteins actin and MLC20, and contraction-inhibiting
      proteins h-caldesmon and calponin was determined by immunoblotting techniques.
      RESULTS: A significant vasospasm occurred in the basilar artery during days 4 to
      21, most prominently on days 7 and 14. There were no significant differences in
      the baseline levels of phosphorylated MLC20 between normal and spastic basilar
      arteries. The increase in MLC20 phosphorylation by PGF2alpha was significantly
      attenuated in the spastic basilar artery in vitro and in vivo (P<0.05). The
      immunoreactivity for actin, h-caldesmon, and calponin in the spastic basilar
      arteries was progressively decreased until day 14 and returned to the normal
      level on day 21. In contrast, protein levels of MLC20 did not significantly
      change during days 0 to 21. CONCLUSIONS: Chronic cerebral vasospasm closely
      resembles the latch state, and temporary deficiencies of contractile proteins may
      result from increased destruction and inhibition of protein synthesis.

PMID- 9756599
TI  - A critical reevaluation of the intraluminal thread model of focal cerebral
      ischemia: evidence of inadvertent premature reperfusion and subarachnoid
      hemorrhage in rats by laser-Doppler flowmetry.
AB  - BACKGROUND AND PURPOSE: The intraluminal thread model for middle cerebral artery
      occlusion (MCAO) has gained increasing acceptance. Numerous modifications have
      been reported in the literature, indicating that the technique has not been
      standardized. The present study was performed to evaluate and optimize the
      reliability of this model. METHODS: One hundred Sprague-Dawley rats were
      subjected to MCAO by 2 different intraluminal filaments. Cortical blood flow was
      continuously monitored over both hemispheres by laser-Doppler flowmetry (LDF). In
      part I (3-0 filament), we evaluated the incidence of adequate MCAO, subarachnoid
      hemorrhage (SAH), intraluminal thrombus formation, and the effects of
      heparinization. In part II (silicone-coated 4-0 filament), we also determined the
      influence of insufficient MCAO on morphological and functional outcome and the
      incidence of postischemic hyperthermia. RESULTS: In part I, SAH occurred in 30%
      and premature reperfusion in 24%. All animals with a decrease in contralateral
      flow had suffered SAH. Thrombus formation was not observed in any group. In part
      II, SAH occurred in 8% and premature reperfusion in 26%. There was no difference
      in outcome between rats with primary MCAO and rats with filament correction.
      Animals with uncorrected premature reperfusion had significantly smaller infarct
      volumes and fewer neurological deficits. CONCLUSIONS: SAH and insufficient MCAO
      may be more common in the intraluminal thread model than previously reported.
      Inadvertent premature reperfusion contributes to the interanimal variability
      associated with this model. The incidence of valid experiments increases with the
      use of a silicone-coated 4-0 filament. Continuous bilateral LDF is indispensable
      to monitor adequate MCAO and is highly sensitive to recognize SAH.

PMID- 9756598
TI  - Diffusion MR imaging during acute subarachnoid hemorrhage in rats.
AB  - BACKGROUND AND PURPOSE: We analyzed the temporal and spatial pattern of water
      diffusion changes during acute subarachnoid hemorrhage (SAH) in rat brain to
      identify factors contributing to the acute pathophysiology of SAH. METHODS:
      Subarachnoid hemorrhage was remotely induced via perforation of the circle of
      Willis with an endovascular suture during MR imaging. A fast echo-planar imaging
      technique was used to acquire 60 maps of the apparent diffusion coefficient (ADC)
      beginning 1 min before and continuing for 11 min after induction of SAH. A high
      resolution spin-echo diffusion sequence was used to follow diffusion changes over
      6 h after SAH. Sham-operated control (n=3), nonheparinized (n=6), and heparinized
      (n=5) groups were studied. RESULTS: Sham-operated control animals did not show
      ADC changes over time. In both SAH groups, however, a sharp decline of ADC within
      2 min of SAH was consistently observed in the ipsilateral somatosensory cortex.
      These decreases in diffusion then spread within minutes over the ipsilateral
      hemisphere. Similar ADC decreases on the contralateral side started with a
      further time delay of 1 to 3 min. From 30 min onward, the extent of the diffusion
      abnormality decreased progressively in the nonheparinized animals. No recovery
      was observed in heparinized rats. CONCLUSIONS: MR diffusion imaging allows new
      insight into the pathophysiology of acute SAH: The spatial and temporal pattern
      of diffusion changes suggests the initial occurrence of acute vasospasm and
      subsequently "spreading depolarization" of brain tissue. Persistent hemorrhage in
      heparinized animals was reflected by early decline of ADC values throughout the
      entire brain.

PMID- 9756600
TI  - Optimal depth and duration of mild hypothermia in a focal model of transient
      cerebral ischemia: effects on neurologic outcome, infarct size, apoptosis, and
      inflammation.
AB  - BACKGROUND AND PURPOSE: Mild hypothermia is possibly the single most effective
      method of cerebroprotection developed to date. However, many questions regarding
      mild hypothermia remain to be addressed before its potential implementation in
      the treatment of human stroke. Here we report the results of 2 studies designed
      to determine the optimal depth and duration of mild hypothermia in focal stroke
      and its effects on infarct size, neurological outcome, programmed cell death, and
      inflammation. METHODS: Rats underwent a 2-hour occlusion of the left middle
      cerebral artery. In the first study (I) animals were kept (intraischemically) at
      either 37 degreesC (n=8), 33 degreesC (n=8), or 30 degreesC (n=8). Study II
      consisted of 4 groups: (1) controls (37 degreesC, n=10), (2) 30 minutes of
      hypothermia started at ischemic onset (33 degreesC, n=9), (3)1 hour (33 degreesC,
      n=8), and (4) 2 hours (33 degreesC, n=8). Brain temperature was measured by a
      thermocouple probe placed in the contralateral cortex. After suture removal, all
      animals were rewarmed and reperfused for 22 hours (I) or 70 hours (II). RESULTS:
      Mild hypothermia to 33 degreesC or 30 degreesC was neuroprotective (17+/-7% and
      27+/-6%, respectively) relative to controls (53+/-8%, P<0.02), but 33 degreesC
      was better tolerated and recovery from anesthesia was faster. The neurological
      score of hypothermic animals was significantly better than that of controls (I &
      II) at both 24 and 72 hours postischemia except for the 30-minute group (II),
      which showed no improvement. In Study II, 2 hours of hypothermia reduced injury
      by 59%, 1 hour reduced injury by 84% whereas 30 minutes did not reduce injury.
      Normalized for infarct size, 2 hours of mild hypothermia decreased neutrophil
      accumulation by 57% whereas both 1 hour and 30 minutes had no effect. At 72
      hours, 1 and 2 hours of mild hypothermia decreased transferase dUTP nick-end
      labeling (TUNEL) staining by 78% and 99%, respectively, and 30 minutes of
      hypothermia had no effect. CONCLUSIONS: Intraischemic mild hypothermia must be
      maintained for 1 to 2 hours to obtain optimal neuroprotection against ischemic
      cell death due to necrosis and apoptosis.

PMID- 9756601
TI  - Cationic polymer and lipids enhance adenovirus-mediated gene transfer to rabbit
      carotid artery.
AB  - BACKGROUND AND PURPOSE: Improvement of efficiency of gene transfer to endothelium
      could be useful for several applications. We tested the hypothesis that cationic
      nonviral molecules augment adenovirus-mediated gene transfer to blood vessels,
      perhaps by alteration of the surface charge of adenovirus and facilitation of
      binding to endothelium. METHODS: Carotid arteries from rabbits were incubated in
      vitro for 0.5 to 2 hours with an adenoviral vector alone or noncovalent complexes
      of adenovirus with poly-L-lysine (a cationic polymer) or lipofectin (a cationic
      lipid). Binding of adenovirus to the vessels was evaluated immediately after
      incubation with virus, and assay of transgene (ss-galactosidase) activity and
      histochemistry were performed 24 hours after gene transfer. To determine whether
      cationic molecules can be used to augment alteration of vascular function by
      adenovirus-mediated gene transfer, we also examined effects on gene transfer of
      endothelial nitric oxide synthase. RESULTS: Assay of ss-galactosidase activity
      indicated that both cationic molecules increased transgene expression in vessels
      by approximately 5- to 6-fold. In contrast, when endothelium was removed from the
      vessels after gene transfer, poly-L-lysine and lipofectin did not significantly
      increase transgene activity. Histochemistry for ss-galactosidase also suggested
      that the adenovirus-cationic molecule complexes augmented transgene expression
      mainly in the endothelium. In addition, we found that complexing adenovirus with
      cationic molecules increased binding of adenovirus to the vessels. After gene
      transfer with recombinant adenovirus containing endothelial nitric oxide
      synthase, calcium ionophore (A23187) produced greater relaxation of vessels
      treated with adenovirus complexed with poly-L-lysine or lipofectin than those
      treated with adenovirus alone. CONCLUSIONS: Cationic molecules improve the
      efficiency of adenovirus-mediated gene transfer to blood vessels.

PMID- 9756602
TI  - Matrix metalloproteinases and TIMPs are associated with blood-brain barrier
      opening after reperfusion in rat brain.
AB  - BACKGROUND AND PURPOSE: Reperfusion disrupts cerebral capillaries, causing
      cerebral edema and hemorrhage. Middle cerebral artery occlusion (MCAO) induces
      the matrix-degrading metalloproteinases, but their role in capillary injury after
      reperfusion is unknown. Matrix metalloproteinases (MMPs) and tissue inhibitors to
      metalloproteinases (TIMPs) modulate capillary permeability. Therefore, we
      measured blood-brain barrier (BBB) permeability, brain water and electrolytes,
      MMPs, and TIMPs at multiple times after reperfusion. METHODS: Adult rats
      underwent MCAO for 2 hours by the suture method. Brain uptake of 14C-sucrose was
      measured from 3 hours to 14 days after reperfusion. Levels of MMPs and TIMPs were
      measured by zymography and reverse zymography, respectively, in contiguous
      tissues. Other rats had water and electrolytes measured at 3, 24, or 48 hours
      after reperfusion. Treatment with a synthetic MMP inhibitor, BB-1101, on BBB
      permeability and cerebral edema was studied. RESULTS: Brain sucrose uptake
      increased after 3 and 48 hours of reperfusion, with maximal opening at 48 hours
      and return to normal by 14 days. There was a correlation between the levels of
      gelatinase A at 3 hours and the sucrose uptake (P<0.05). Gelatinase A (MMP-2) was
      maximally increased at 5 days, and TIMP-2 was highest at 5 days. Gelatinase B and
      TIMP-1 were maximally elevated at 48 hours. The inhibitor of gelatinase B, TIMP
      1, was also increased at 48 hours. Treatment with BB-1101 reduced BBB opening at
      3 hours and brain edema at 24 hours, but neither was affected at 48 hours.
      CONCLUSIONS: The initial opening at 3 hours correlated with gelatinase A levels
      and was blocked by a synthetic MMP inhibitor. The delayed opening, which was
      associated with elevated levels of gelatinase B, failed to respond to the MMP
      inhibitor, suggesting different mechanisms of injury for the biphasic BBB injury.

PMID- 9756603
TI  - beta-Amyloid precursor protein and ss-amyloid peptide immunoreactivity in the rat
      brain after middle cerebral artery occlusion: effect of age.
AB  - BACKGROUND AND PURPOSE: Previous studies have shown that the ss-amyloid precursor
      protein (ssAPP) is upregulated after cerebral ischemia and that the ss-amyloid
      (Ass) fragment may be toxic to brain cells. Although stroke in humans usually
      afflicts the elderly, most experimental studies on the nature of cerebral
      ischemia have used young animals. To test the hypothesis that the upregulation
      and/or persistence of amyloidogenic proteins is exacerbated in aged rats after
      cerebral ischemic stroke, we studied the expression of ssAPP and its proteolytic
      product Ass in the brains of young and old rats 7 days after temporary cerebral
      ischemia. METHODS: Focal cerebral ischemia was produced by reversible occlusion
      of the right middle cerebral artery in 3- and 20-month-old male Sprague-Dawley
      rats. After 1 week, brains were removed and immunostaining was performed for
      ssAPP, Ass, and ED1 for macrophages and glial fibrillary acidic protein (GFAP).
      RESULTS: Histological staining revealed that the degree of necrotic cavitation in
      the infarct core was relatively less in aged rats than in young rats, suggesting
      a slower pace of degenerative change and/or tissue removal in older animals.
      ssAPP immunoreactivity was robustly increased, primarily in macrophage-like, ED1
      positive cells in the infarct core and in the penumbra of both young and aged
      animals. Ass immunoreactivity was evident in GFAP-positive astrocytic somata and
      processes, and also in clusters of small spherical structures in the penumbra.
      These Ass-immunoreactive minispheres were more numerous in aged rats than in
      young rats. CONCLUSIONS: The presence of ssAPP and Ass immunoreactivity in the
      infarct core and penumbra indicates that cerebral ischemia promotes conditions
      that are favorable to the focal accumulation of ssAPP and its proteolytic
      fragments, especially in the aged brain.

PMID- 9756604
TI  - Quality of full and final publications reporting acute stroke trials: a
      systematic review.
AB  - BACKGROUND AND PURPOSE: Several studies have shown that the quality of reporting
      of trials throughout medicine is variable and often poor. We report on the
      quality of the final reports of randomized controlled trials (RCTs) of drug
      therapies assessed in acute stroke. METHODS: English-language reports published
      up to the end of 1996 relating to completed RCTs in acute stroke were identified
      from electronic searches of the Cochrane Stroke Review Group database of stroke
      trials and the Cochrane Controlled Trials Register (CD-ROM issue 1, 1997, of the
      Cochrane Library). Report quality was assessed with the 33 criteria of the
      CONSORT statement and 53 additional factors relevant to acute stroke or trials in
      general. Trial quality was also assessed with a 7-point scale. RESULTS: Up to
      1996, 114 RCTs were published which involved 20 536 patients (median, 80; range,
      16 to 1267 per trial); 39 (35.5%) of these were published in Stroke. The median
      total report quality was 40/86 (range, 15 to 61) for all criteria and 19/33
      (range, 9 to 29) for the CONSORT criteria alone. Although adequate information
      was given in the introduction and discussion sections of most reports,
      insufficient details were given on methods, assignment of patients to treatment
      groups, statistical analyses, the prevalence of risk factors, and assessment of
      outcomes. Report quality has improved between 1956 and 1996 (Spearman correlation
      coefficient [rs], 0.575; 95% confidence interval [CI], 0. 439 to 0.685) and was
      superior in large trials (rs=0.434; 95% CI, 0. 274 to 0.571). Although report
      quality was related to trial quality (rs=0.675; 95% CI, 0.563 to 0.763), it was
      not related to journal impact factor (rs=0.170; 95% CI, -0.015 to 0.344). Trials
      with a positive outcome tended to be less well reported than those with a neutral
      or negative outcome (rs=-0.192; 95% CI, -0.351 to -0.011). CONCLUSIONS: The
      overall quality of study reports for parallel group RCTs in acute stroke is poor
      but appears to be improving with time and in parallel with an increase in trial
      size. Reports often lack detailed information on the methods of randomization,
      concealment of allocation, and statistical analysis, all factors which can, if
      undertaken poorly, affect trial results and validity. It is vital that future
      trials are adequately reported; we believe that authors should follow the CONSORT
      guidelines and that referees and editors should ensure this happens.

PMID- 9756605
TI  - Evaluation of carotid artery stenosis by power doppler imaging.

PMID- 9756606
TI  - Evaluation of carotid artery stenosis by power doppler imaging 

PMID- 9756608
TI  - Abstracts of literature 

PMID- 9756607
TI  - Two chinese patients with vertebrobasilar dolichoectasia.

PMID- 9756609
TI  - The following is a list of major ongoing studies about stroke. Information about
      other multicenter studies that might be included in this list should be submitted
      to the stroke editorial office by the principal investigator. The list will
      appear in the february, june, and october issues of stroke 

PMID- 9756610
TI  - Roles of aggrecan, a large chondroitin sulfate proteoglycan, in cartilage
      structure and function.
AB  - Aggrecan, a large aggregating proteoglycan, is one of the major structural
      components of cartilage. Its core protein contains three glubular domains and two
      glycosaminoglycan-attachment domains. These domains play various roles to
      maintain cartilage structure and function. An N-terminal globular domain binds
      hyaluronan and link protein to form huge aggregates. The chondroitin sulfate (CS)
      chains attach to the CS domain and provide a hydrated, viscous gel that absorbs
      compressive load. Two autosomal recessive chondrodysplasias, cartilage matrix
      deficiency (cmd) in mice and nanomelia in chicken are both caused by aggrecan
      gene mutations. Cmd homozygotes die shortly after birth, while the heterozygotes
      are born normal. However, cmd heterozygotes develop late onset of spinal
      disorder, which suggests aggrecan as a candidate gene predisposing individuals to
      spinal problems. Nanomelia is a useful model to elucidate intracellular
      trafficking of proteoglycans. Further studies on aggrecan will lead to
      prophylaxis and treatment of joint destructive diseases such as osteoarthrosis
      and to elucidation of cartilage development, which is essential for skeletal
      formation.

PMID- 9756611
TI  - CYP51-like gene of Mycobacterium tuberculosis actually encodes a P450 similar to
      eukaryotic CYP51.
AB  - A CYP51-like gene (Z80226) of Mycobacterium tuberculosis was expressed in
      Escherichia coli. The product exhibited absorption spectra characteristic of
      P450. The expressed P450 formed a stoichiometric complex with ketoconazole, one
      of the specific ligands of CYP51. These findings indicate that the CYP51-like
      gene of M. tuberculosis actually encodes a P450 having active-site environments
      similar to those of CYP51, confirming the predicted orthologous nature of this
      gene to eukaryotic CYP51. Although eukaryotic CYP51s are membrane-binding
      proteins, the expressed product was accumulated only in the soluble fraction of
      the host cells.

PMID- 9756612
TI  - Cationic liposome-mediated efficient induction of type I interferons by a low
      dose of poly I:poly C in mouse cell lines.
AB  - Double-stranded polyriboinosinic acid:polyribocytidylic acid (poly I:poly C) is a
      powerful inducer of type I interferons (IFNs). However, the dose of poly I:poly C
      required for efficient IFN induction is so high as occasionally to be cytotoxic.
      In this work, we examined the IFN-inducibility of poly I:poly C complexed with
      several cationic reagents in mouse fibroblast L cells and found that Lipofectin
      and LipofectACE can induce the production of a substantial amount of type I IFNs
      (mostly beta-type) even at a two-order lower dose compared with poly I:poly C
      alone. Such effects of poly I:poly C were optimal at 0.1 microgram/ml for 2-10
      microgram/ml of Lipofectin and LipofectACE. These conditions caused no
      significant cytotoxicity in the recipient cells. Furthermore, a short treatment
      (less than 10 min) with the complexes was sufficient for the maximum induction.
      This IFN induction method was applicable to other cell types and other species
      including human. Hence, our observations may pave the way for clinical
      application of the IFN inducer.

PMID- 9756613
TI  - Kinetics of slow reversible inhibition of human muscle creatine kinase by planar
      anions.
AB  - The toxicity of NO3- and NO2- to mammals has been widely publicized. However, the
      kinetic mechanism of inhibition of human muscle creatine kinase by NO3- and NO2-
      has not been explored. The kinetic theory of the substrate reaction during the
      modification of enzyme activity previously described by Tsou (Adv. Enzymol.
      Related Areas Mol. Biol. 1988, 61, 381-436) has been applied to a study of the
      kinetics of slow reversible inhibition of human muscle creatine kinase by planar
      anions (NO3- and NO2-). The kinetic equation of the substrate reaction was
      derived from theoretical analysis and experimental data, then simplified. The
      microscopic rate constants for the reaction of the inhibitors with the enzyme
      were obtained from the simplified equation for the substrate reaction in the
      presence of the inhibitors. The results show that the apparent forward rate
      constant A is dependent on ATP concentration, indicating competition between the
      inhibitor (NO3- or NO2-) and ATP. The results also suggest that binding of
      creatine-MgADP and the anion with the enzyme is very tight, since their binding
      constants are much higher than those for normal substrates.

PMID- 9756614
TI  - Substrate specificity of human monoamine (M)-form phenol sulfotransferase:
      preparation and analysis of Dopa 3-O-sulfate and Dopa 4-O-sulfate.
AB  - Upon two-dimensional thin-layer separation, the sulfated L-3, 4
      dihydroxyphenylalanine (L-DopaS) generated enzymatically was found to co-migrate
      with only one of the two ninhydrin-stained spots corresponding to the two
      sulfated forms (3-O-sulfate and 4-O-sulfate) of synthetic L-DopaS. To clarify
      precisely the identity of the enzymatically generated L-DopaS, the two sulfated
      forms of synthetic L-DopaS were separated and purified using high performance
      liquid chromatography. Purified L-Dopa 3-O-sulfate and L-Dopa 4-O-sulfate were
      identified by 1H-nuclear magnetic resonance (NMR) spectrometry and used as
      standards in the analysis of the L-DopaS generated during metabolic labeling of
      HepG2 human hepatoma cells or enzymatic assay using recombinant human monoamine
      (M)-form phenol sulfotransferase. The results obtained demonstrated unequivocally
      the generation of L-Dopa 3-O-sulfate, indicating the specificity of the M-form
      phenol sulfotransferase being for the meta-hydroxyl group of L-Dopa.

PMID- 9756615
TI  - Kinetic measurement of the interaction between a lysozyme and its immobilized
      substrate analogue by means of surface plasmon resonance.
AB  - A method for evaluating the association and dissociation rate constants of
      interaction between a lysozyme and its substrate analogue, an immobilized p
      aminophenyl-tri-N-acetyl-beta-chitotrioside, by means of surface plasmon
      resonance has been developed. Site-specific immobilization of p-aminophenyl-tri-N
      acetyl-beta-chitotrioside, which is a product of p-nitrophenyl-tri-N-acetyl-beta
      chitotrioside, on carboxymethyldextran linked to the surface of the cuvette of
      the instrument, IAsys, was carried out by catalysis with EDC/NHS. The kinetic
      parameters of the interaction between hen or human lysozyme and the immobilized
      substrate analogue indicated that a larger dissociation constant of the human
      lysozyme-immobilized substrate analogue complex depended on a smaller association
      rate constant. The kinetic parameters of the interaction between the immobilized
      substrate analogue and a mutant hen lysozyme, in which Arg14 and His15 are
      deleted, with higher activity than the wild type hen lysozyme were measured. It
      was suggested that the higher activity of the mutant lysozyme was due to faster
      removal of the substrate from the active site cleft and/or the formation of a
      stabler and better complex as to hydrolysis.

PMID- 9756616
TI  - Isolation of the gene and characterization of the enzymatic properties of a major
      exoglucanase of humicola grisea without a cellulose-binding domain.
AB  - An exoglucanase gene was cloned from a cellulolytic fungus, Humicola grisea. DNA
      sequencing of this gene, designated as exo1, revealed that it contained four
      introns in the coding region. The deduced amino acid sequence of EXO1 was 451
      amino acids in length and showed 57.7% identity with that of H. grisea
      cellobiohydrolase 1 (CBH1), but lacked the typical domain structures of a
      cellulose-binding domain and a hinge region. Transcriptional analysis of the exo1
      and cbh1 genes showed that the expression of these genes was induced by Avicel,
      and repressed in the presence of glucose. The exo1 gene was expressed in
      Aspergillus oryzae, and the recombinant EXO1 protein was purified. EXO1 and CBH1
      produced by A. oryzae showed relatively higher activity toward Avicel, but showed
      much lower activity toward carboxymethyl cellulose (CMC) and p-nitrophenyl-beta-D
      cellobioside (PNPC), than H. grisea endoglucanase 1 (EGL1). The addition of a
      cellulose-binding domain and a hinge region to EXO1 caused decreases in its
      enzymatic activities as well as the deletion of the cellulose-binding domain from
      CBH1. EXO1 showed relatively weak or no synergistic activity toward Avicel with
      H. grisea endoglucanases, but showed a significant level of apparent synergism
      with H. grisea CBH1 and Trichoderma reesei EGLI. CBH1 showed a significant level
      of apparent endo-exo synergism with H. grisea and T. reesei endoglucanases. H.
      grisea has at least two different types of major exoglucanase components and
      shows strong cellulolytic activity through synergism with cellulase components
      including EXO1 and CBH1.

PMID- 9756617
TI  - Alpha 1,6-linked fucose affects the expression and stability of polysialic acid
      carrying glycoproteins in Chinese hamster ovary cells.
AB  - To determine the effect of alpha1,6-linked fucose modification of N-glycans on
      the expression of polysialic acids (PSAs), the expression of PSAs in a fucose
      lacking mutant of Chinese hamster ovary (CHO) cells, Lec13, was compared with
      that in CHO K1 cells. PSA synthase activity in these cells and the antennary
      structures of N-glycans associated with the neural adhesion molecule (NCAM),
      which is a major PSA-carrying glycoprotein, did not differ between the two types
      of cells. Metabolic labeling of cells with [3H]glucosamine for 48 h followed by
      immunoprecipitation with anti-PSA monoclonal antibodies revealed that the amount
      of labeled PSA-carrying glycoproteins obtained from Lec13 cells was 10-times less
      than that from K1 cells, although the incorporation of [3H]glucosamine into total
      extracts and NCAM was almost the same. In contrast, when cells were pulse labeled
      with [35S]methionine followed by a 1 h chase, there was not such a great
      difference in PSA-carrying protein synthesis between K1 and Lec13 cells. However,
      during a prolonged chase period, PSA-carrying proteins rapidly decreased in Lec13
      cells, whereas those in K1 cells did not change. The degradation of PSA-carrying
      glycoproteins in Lec13 cells was partly prevented when the cells were grown in
      fucose-containing medium. Therefore, fucose modification of core N-glycans may
      affect the efficient expression of PSAs through the intracellular stability of
      PSA-carrying glycoproteins.

PMID- 9756619
TI  - Expression and characterization of a very low density lipoprotein receptor
      variant lacking the O-linked sugar region generated by alternative splicing.
AB  - The very low density lipoprotein receptor (VLDLR) gene contains an exon encoding
      a region of clustered serine and threonine residues immediately outside the
      membrane-spanning sequence, and this region has been proposed to be the site of
      clustered O-linked carbohydrate chains. Two forms of VLDLR transcripts, with and
      without the O-linked sugar region, are generated through alternative splicing.
      Reverse transcription polymerase chain reaction with RNAs from various rabbit
      tissues revealed that the VLDLR transcript with the O-linked sugar region (type-1
      VLDLR) is the major transcript in heart and muscle, while the VLDLR transcript
      without the O-linked sugar region (type-2 VLDLR) predominates in non-muscle
      tissues, including cerebrum, cerebellum, kidney, spleen, adrenal gland, testis,
      ovary, and uterus. Hamster fibroblasts expressing type-2 VLDLR bound with
      relatively low affinity to beta-migrating very low density lipoprotein compared
      with type-1 VLDLR-transfected cells. In contrast, the internalization,
      dissociation, and degradation of the ligand were not significantly impaired in
      either type of VLDLR-transfected cell. The receptor proteins in type-2 VLDLR
      transfected cells underwent rapid degradation and accumulated in the culture
      medium, while those in type-1 VLDLR-transfected cells were stable and resistant
      to proteolytic cleavage. Analysis of the O-linked sugars of both types of
      transfected cells suggested that the O-linked sugar region is the major site for
      O-glycosylation.

PMID- 9756618
TI  - Microtubule-stimulated phosphorylation of tau at Ser202 and Thr205 by cdk5
      decreases its microtubule nucleation activity.
AB  - Phosphorylation of tau, a heat-stable neuron-specific microtubule-associated
      protein, by cdk5 was stimulated in the presence of microtubules (MTs). This
      stimulation was due to an increased phosphorylation rate and there was no
      increase in total amount of phosphorylation. Two-dimensional phosphopeptide map
      analysis showed that MTs stimulated phosphorylation of a specific peptide. Using
      Western blotting with antibodies that the recognized phosphorylation-dependent
      epitopes within tau, the phosphorylation sites stimulated by the presence of MTs
      were found to be Ser202 and Thr205 (numbered according to the human tau isoform
      containing 441 residues). MT-dependent phosphorylation at Thr205 was observed in
      situ in rat cerebrum primary cultured neurons. Stimulated phosphorylation at
      Ser202 and Thr205 decreased the MT-nucleation activity of tau, which is in
      contrast to MT-independent phosphorylation at Ser235 and Ser404.

PMID- 9756620
TI  - Deletion analysis of protein kinase Calpha reveals a novel regulatory segment.
AB  - Using a combined pharmacological and genetic approach, we have identified aa 260
      280 in the C2 region as a critical factor in the catalytic function of protein
      kinase Calpha (PKCalpha). Progressive truncations from the N-terminus as well as
      selected internal deletion mutants were expressed in Saccharomyces cerevisiae and
      tested for altered sensitivity to dequalinium, a PKC inhibitor whose target site
      was previously mapped to the catalytic domain. PKC mutants representing
      truncations of up to 158 amino acid residues (aa) from the N-terminus (ND84 and
      ND158) displayed 60-63% inhibition of kinase activity by 50 microM dequalinium,
      somewhat more sensitive than the wild-type PKCalpha enzyme (45% inhibition).
      Mutant ND262, lacking N-terminal aa 1-262, was inhibited by almost 72% with 50
      microM dequalinium, but mutant ND278, which lacked an additional 16 aa, was
      inhibited by only 9% of total activity. This result suggests that a C-terminal
      segment of the C2 region (aa 263-278) influences inhibition by dequalinium at low
      micromolar concentrations. An internal deletion mutant (D260-280) which retains
      the entire primary structure of PKCalpha except for aa 260-280, was similarly
      inhibited by only 4% with 50 microM dequalinium. In the absence of dequalinium
      and despite the presence of a nearly complete regulatory domain, this mutant
      exhibited constitutive activity (both in vitro and in a phenotypic assay with S.
      cerevisiae) that could not be further stimulated even by the potent activator
      TPA. Taken together, our findings suggest that, in the native structure of
      PKCalpha, the segment described by aa 260-280 regulates PKCalpha activity and
      influences the sensitivity of PKCalpha to dequalinium.

PMID- 9756621
TI  - Identification of arg-30 as the essential residue for the enzymatic activity of
      Taiwan cobra phospholipase A2.
AB  - Taiwan cobra (Naja naja atra) phospholipase A2 (PLA2) was inactivated by arginine
      specific reagents, phenylglyoxal and 1, 2-cyclohexanedione. Kinetic analyses of
      the modification reaction revealed that the inactivation of PLA2 followed pseudo
      first-order kinetics and the loss of activity was correlated with the
      incorporation of one molecule of modification reagent per PLA2 molecule. This was
      confirmed by the results of amino acid composition determination, that showed
      that a marked decrease in enzymatic activity was associated with the modification
      of one arginine residue. Tryptic cleavage of the modified protein and
      microsequencing revealed that Arg-30 was the functionally essential residue. The
      incorporation of a modifier into the PLA2 did not significantly affect the
      secondary structure of the enzyme, as revealed by the CD spectrum, and Ca2+
      binding of the modified PLA2 was unaffected. Nevertheless, the nonpolarity of the
      active site of PLA2 markedly decreased with the arginine modification, as
      evidenced by the decreases in the enhancement of Trp and 8-anilinonaphthalene
      sulfonate fluorescence. These results, together with those of X-ray
      crystallographic analysis of N. naja atra PLA2 [Scott et al. (1990) Science 250,
      1541-1546], demonstrate that Arg-30 is one of the residues involved in the
      interfacial binding of a PLA2 molecule with its substrate.

PMID- 9756622
TI  - Topological mutation of Escherichia coli dihydrofolate reductase.
AB  - Proteins appear to contain structural elements which determine the folded
      structure. If such elements are present, the order of structural elements in the
      primary structure, i.e. the chain topology, can be disregarded for building of
      the folded tertiary structure, when they are properly connected to each other by
      proper linkers. To experimentally examine this, "topological" mutants (designated
      as GHF33 and GHF34) of Escherichia coli dihydrofolate reductase (DHFR) were
      designed and constructed by switching two amino acid sequence parts containing
      the betaF strand and betaG-betaH strands in the primary sequence. In this way,
      the chain topology of wild-type DHFR, betaA-->alphaB-->betaB-->alphaC-->betaC-->
      betaD-->alphaE-->betaE-->al phaF-->betaF-->betaG-->betaH, was changed to betaA-
      >alphaB-->betaB-->alphaC-->betaC--> betaD-->alphaE-->betaE-->al phaF-->betaG-
      >betaH-->betaF. Such topological mutant proteins were stably expressed and
      accumulated in E. coli cells, and highly purified. Molecular mass measurements of
      the purified proteins and their proteolytic fragments confirmed that GHF33 and
      GHF34 had the designed sequence. In terms of kcat, the GHF33 and GHF34 proteins
      showed about 10 and 20% of the DHFR activity of the wild-type with Km values of
      3.3 microM (GHF33) and 2.1 microM (GHF34), respectively. The topological mutants
      showed a cooperative two-state transition in urea-induced unfolding experiments
      with DeltaGH2O values of 4.0 and 4.8 kcal/mol. Whereas, the Km and DeltaGH2O
      values for wild-type DHFR were 0.9 microM and 6.1 kcal/mol, respectively. The
      significance of the topological mutations was discussed with respect to protein
      folding and protein evolution.

PMID- 9756623
TI  - Pyrrolidone carboxyl peptidase from the hyperthermophilic Archaeon Pyrococcus
      furiosus: cloning and overexpression in Escherichia coli of the gene, and its
      application to protein sequence analysis.
AB  - A gene for a pyrrolidone carboxyl peptidase (Pcp: EC 3.4.19.3, pyroglutamyl
      peptidase), which removes amino-terminal pyroglutamyl residues from peptides and
      proteins, has been cloned from the hyperthermophilic Archaeon Pyrococcus furiosus
      using its cosmid protein library, sequenced, and expressed in Escherichia coli.
      The DNA sequence encodes a protein containing 208 amino acid residues with
      methionine at the N-terminus. Analysis of the recombinant protein expressed in E.
      coli, including amino acid sequence analysis from the N-terminus by automated
      Edman degradation and ionspray mass spectrometric analysis of the peptides
      generated by enzymatic digestions with lysylendopeptidase and Staphylococcus
      aureus V8 protease, showed its primary structure to be completely identical with
      that deduced from its cDNA sequence. Comparison of the amino acid sequence of P.
      furiosus Pcp (P.f.Pcp) with those of bacterial Pcps revealed that a high degree
      of sequence identity (more than 40%) and conservation of the amino acid residues
      comprising the catalytic triad, Cys142, His166, and Glu79. On the other hand, a
      unique short stretch sequence (positions around 175-185) that is absent in
      bacterial Pcps was found in P.f.Pcp. A similar stretch has also been reported
      recently in the amino acid sequence of Pcp from the hyperthermophilic Archaeon
      Thermococcus litoralis [Littlechild et al., in abstracts of the "International
      Congress on Exthermophiles '98" p. 58 (1998)]. To elucidate their contribution to
      the hyperthermostability of these enzymes, further structural studies are
      required.

PMID- 9756624
TI  - A novel low-density lipoprotein receptor-related protein with type II membrane
      protein-like structure is abundant in heart.
AB  - We report herein the identification of a novel member of the low-density
      lipoprotein receptor (LDLR) family termed LDLR-related protein 4 (LRP4). Murine
      LRP4 cDNA encodes a 1113-amino-acid type II membrane-like protein with eight
      ligand-binding repeats in two clusters. Southern blot analysis of genomic DNA
      from several different organisms suggests the presence of LRP4 homologues in
      chicken lacking the gene encoding apolipoprotein E, which is recognized by the
      ligand-binding repeats of LDLR. LRP4 transcripts were detected almost exclusively
      in heart in mouse and humans. Despite the presence of the ligand-binding repeats,
      COS cells transfected with LRP4 did not show surface-binding of beta-migrating
      very-low-density lipoprotein, suggesting that LRP4 plays a role in a pathway
      other than lipoprotein metabolism.

PMID- 9756625
TI  - Intersubunit structure within heterodimers of medium-chain prenyl diphosphate
      synthases. Formation of a hybrid-type heptaprenyl diphosphate synthase.
AB  - Among prenyltransferases that catalyze the sequential condensation of isopentenyl
      diphosphate with allylic diphosphate to produce prenyl diphosphates with various
      chain lengths and stereochemistries, medium-chain prenyl diphosphate synthases
      are exceptional in that they comprise two dissociable heteromeric protein
      components. These components exist without binding with each other under
      physiological conditions, and neither of them has any prenyltransferase activity
      by itself. In order to elucidate the precise molecular mechanism underlying
      expression of the catalytic function by such a unique two-component system, we
      examined the possibility of forming a hybrid between two of the components of
      three different medium-chain prenyl diphosphate synthases, components I and II of
      heptaprenyl diphosphate synthase from Bacillus subtilis, components I' and II' of
      heptaprenyl diphosphate synthase from Bacillus stearothermophilus, and components
      A and B of hexaprenyl diphosphate synthase from Micrococcus luteus B-P 26. As a
      result, only the hybrid-type combination of component I and component II' gave
      distinct prenyltransferase activity. The hybrid-type enzyme catalyzed the
      synthesis of heptaprenyl diphosphate and showed moderate heat stability, which
      lay between those of the natural enzymes from B. subtilis and B.
      stearothermophilus. There is no possibility of forming a hybrid between the
      heptaprenyl and hexaprenyl diphosphate synthases.

PMID- 9756626
TI  - Phospholipid translocation from the outer to the inner leaflet of synaptic
      vesicle membranes isolated from the electric organ of Japanese electric ray Narke
      japonica.
AB  - The phospholipid translocation from the outer to the inner leaflet of synaptic
      vesicles isolated from the electric organ of the Japanese electric ray, Narke
      japonica, was measured using fluorescent phospholipid probes. Phosphatidylcholine
      (PC), phosphatidylethanolamine (PE), or phosphatidylserine (PS) with a
      fluorescent NBD-labeled short acyl chain at the sn-2 position was mixed with
      purified synaptic vesicles and the probe in the outer leaflet of the membranes
      was reduced with dithionite to quench the fluorescence from time to time. The
      percentage of fluorescence remaining after the dithionite treatment served as an
      index for the phospholipid translocation. The results obtained indicated that
      about 30, 13, and 9% of NBD-PE, NBD-PS, and NBD-PC, respectively, were
      translocated from the outer to the inner leaflet in 3 h. Thus, the translocation
      activity in synaptic vesicle membranes was much higher for PE than for PS, in
      contrast to the previous results obtained with plasma membranes, including
      synaptosomal membranes. The percentages of the phospholipid in the inner leaflet
      at equilibrium were estimated to be 41, 31, and 14% for PE, PS, and PC,
      respectively. The translocation was inhibited by pretreatment with an SH reagent,
      iodoacetamide, indicating the involvement of a proteinaceous translocator. These
      data may provide a biochemical basis for elucidating the mechanisms of membrane
      fusion and exocytosis at nerve endings.

PMID- 9756628
TI  - Effect of long-term ammonia starvation on the oxidation of ammonia and
      hydroxylamine by Nitrosomonas europaea.
AB  - Axenic cultures of the ammonia-oxidizing bacterium Nitrosomonas europaea were
      starved of ammonia (energy source) for up to 342 d. During this time the bacteria
      retained the ability to respond instantly to ammonia (1 mM) or hydroxylamine (0.1
      mM) amendment by oxidizing it to nitrite without initial protein synthesis. In
      vivo, the ability to oxidize amended ammonia stayed almost constant during the
      starvation period, but a drop in the hydroxylamine oxidation rate (to 33%) was
      observed after 4 wk of starvation when exogenous hydroxylamine was supplied as
      sole energy source. In contrast, it has been shown that the level and in vitro
      activity of hydroxylamine oxidoreductase were not significantly affected during
      the starvation period. Only minor changes were detected between the protein
      patterns on one-dimensional SDS-PAGE of growing and starved cells. Thus, it is
      concluded that the activities of the energy-generating enzymes in N. europaea
      were not affected during long-term ammonia starvation.

PMID- 9756627
TI  - An endogenous target protease, SAM-P26, of Streptomyces protease inhibitor (SSI):
      primary structure, enzymatic characterization, and its interaction with SSI.
AB  - We have been focusing on the potent involvement of the molecular interaction
      between a protease and a protease inhibitor in the physiological or morphological
      regulation of Streptomyces cells producing them [Taguchi et al. (1995) J.
      Bacteriol. 177, 6638-6643; Suzuki et al. (1997) J. Bacteriol. 179, 430-438]. In
      this study, an extracellular protease, termed SAM-P26, was isolated as a target
      of endogenous protease inhibitor (SSI) from the culture medium of an SSI non
      producing mutant strain derived from Streptomyces albogriseolus S-3253. Complete
      amino acid sequence determination revealed that SAM-P26 is identical to a protein
      encoded by the SAM-P20D gene, which was previously found to be located downstream
      of the gene for SAM-P20, another target protease of SSI. Based on the sequence
      homology, SAM-P26 was categorized as a member of the chymotrypsin family like SAM
      P20. Sequence similarity between SAM-P26 and SAM-P20 was immunologically
      demonstrated by Western blot analysis using anti-SAM-P20 antiserum. The molecular
      mass (26 kDa) of SAM-P26 estimated by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis was much higher than that calculated from the amino acid sequence
      of SAM-P26 (18,376.8 Da) and that of the S-pyridylethylated form (18,808.4 Da) of
      SAM-P26 determined by Matrix-assisted Laser Desorption/Ionization-Time of
      Flight/Mass Spectrometry. Analytical gel-filtration analysis revealed that SAM
      P26 exists as a monomer (18.8 kDa) in the native state. The results as to
      substrate specificity and inhibitor sensitivity indicated SAM-P26 exhibits
      chymotrypsin-like activity. For the proteolytic activity, the optimal pH was 10.5
      and the optimal temperature was 60 degreesC. The complex formation of SAM-P26
      with SSI was confirmed by native-PAGE analysis.

PMID- 9756629
TI  - Activities of mutant Sar1 proteins in guanine nucleotide binding, GTP hydrolysis,
      and cell-free transport from the endoplasmic reticulum to the Golgi apparatus.
AB  - Sar1p belongs to a unique subfamily of the small GTPase superfamily and is
      essential for the formation of vesicles that transport proteins from the
      endoplasmic reticulum to the Golgi apparatus. We have obtained mutants of the
      yeast SAR1 gene, which show several different phenotypes in cell growth and
      protein transport [Nakano, A. , Otsuka, H., Yamagishi, M., Yamamoto, E., Kimura,
      K., Nishikawa, S., and Oka, T. (1994) J. Biochem. 116, 243-247; Yamanushi, T.,
      Hirata, A., Oka, T., and Nakano, A. (1996) ibid. 120, 452-458]. In this study, we
      have purified five mutant Sar1 proteins using an Escherichia coli expression
      system and characterized their biochemical properties in detail. Three of them
      prefer GDP binding to GTP binding and are thus regarded as GDP-form mutants, and
      one is insensitive to the GTPase-activating protein and is almost fixed in the
      GTP-bound state. The GDP mutants are defective in vesicle formation in vitro,
      whereas the GTP mutant can drive vesicle formation but not the overall transport
      to the Golgi. These mutants will be useful for further understanding of the
      regulation of the GTPase cycle of Sar1p.

PMID- 9756630
TI  - Characterization of the initial steps of precursor import into rat liver
      mitoplasts.
AB  - Mitochondria have two independent protein-import machineries, one in the outer
      membrane (the Tom system) and the other in the inner membrane (the Tim system).
      Here, we have characterized the initial steps of precursor import into rat liver
      mitoplasts. The import reaction was separated into two stages, consisting of
      precursor binding to the mitoplasts at 0-10 degreesC, and a subsequent chase
      reaction at 30 degreesC. This assay revealed four distinct precursor-import
      steps: DeltaPsi-dependent initial binding of the precursor, precursor transfer to
      the Tim23-Tim17 stage, DeltaPsi-dependent translocation of the presequence across
      the inner membrane, and the complete translocation of the mature portion of the
      precursor. Antibodies against the intermembrane space domain of Tim23 inhibited
      neither the precursor binding nor the subsequent translocation of the presequence
      across the inner membrane. In contrast, the antibodies inhibited the complete
      translocation of the mature domain of the precursor across the inner membrane.
      Immunoprecipitation with anti-Tim23 IgGs revealed that the precursor-Tim23
      complex increased with time and temperature after the initial targeting of the
      precursor to the mitoplasts. These results suggest that the precursor is first
      targeted to the inner membrane component DeltaPsi-dependently, then transferred
      to the Tim system consisting of Tim23-Tim17, and finally imported into the
      matrix.

PMID- 9756631
TI  - Protection of mammalian cells from the toxicity of bleomycin by expression of a
      bleomycin-binding protein gene from Streptomyces verticillus.
AB  - A gene, blmA, encodes a bleomycin (Bm)-binding protein, designated BLMA, from Bm
      producing Streptomyces verticillus and confers resistance to Bm in Streptomyces
      and Escherichia coli cells. In the present study, by transfection of the gene
      into COS-1 cells with a plasmid designated pEF-BOS/blmA, which contains a strong
      promoter from the human polypeptide chain elongation factor 1alpha, we
      transiently overproduced BLMA at a high level of approximately 4% of the whole
      cell protein. Although NIH/3T3 cells transfected with pEF-BOS/blmA, designated
      NIH/3T3-BR cells, stably expressed BLMA, its expression level was about 0.1% of
      the total protein. Using an anti-BLMA monoclonal antibody reported previously
      [Sugiyama et al. (1995) FEBS Lett. 362, 80-84], we revealed that BLMA is
      localized in the nucleus of pEF-BOS/blmA-transfected COS-1 and NIH/3T3-BR cells.
      Semi-permeabilized nuclear transport experiments showed that BLMA penetrates the
      nuclear envelope by energy- and transporter-independent passive diffusion,
      suggesting that the karyophilic nature of BLMA may be due to the acidic nature of
      the protein. NIH/3T3-BR cells were 130-fold more resistant to Bm than the host
      cells. NIH/3T3 cells exhibited a swollen nuclear envelope and a malformed spindle
      body and overexpressed at least 4 kinds of stress proteins including calreticulin
      and mitochondrial matrix protein P1 when exposed to 25 microg/ml of Bm, whereas
      NIH/3T3-BR cells grew without morphological alteration and expressed no stress
      proteins under the same conditions. Furthermore, reverse transcription-polymerase
      chain reaction and Northern blot analysis showed that the expression of
      interleukin-6, an inflammatory cytokine, is activated by addition of Bm in
      NIH/3T3 cells, but not in the NIH/3T3-BR cells. These results suggest that BLMA
      contributes to protection of mammalian cells from the inflammatory effect of Bm.

PMID- 9756632
TI  - Single-step purification and characterization of MBP (maltose binding protein)
      DnaJ fusion protein and its utilization for structure-function analysis.
AB  - DnaJ is a molecular chaperone, which contains a zinc finger-like motif and
      cooperates with DnaK to mediate the folding of newly synthesized and denatured
      proteins. DnaJ was overproduced and purified using the maltose binding protein
      (MBP) fusion vector. The fusion protein (MBP-DnaJ) was expressed in a soluble
      form in Escherichia coli and purified to homogeneity using amylose resin in a
      single step. The UV-visible absorption spectrum of MBP-DnaJ showed peaks at 355
      and 475 nm. Moreover, these absorption peaks disappeared upon treatment with
      ethylenediaminetetraacetic acid (EDTA) or p-hydroxymercuriphenylsulfonic acid
      (PMPS). Inductively coupled plasma (ICP) spectrometry demonstrated that MBP-DnaJ
      contains Fe ions as well as Zn ions. MBP-DnaJ mediated the replication of the
      lambda phage in vivo, stimulated the ATPase activity of DnaK and prevented the
      aggregation of denatured rhodanase, indicating that fusion of MBP to the N
      terminal of DnaJ does not affect the functions of DnaJ. To study the roles of
      bound metal ions, metal-free MBP-DnaJ, and MBP-DnaJ containing 2 Zn ions were
      prepared. MBP-DnaJ containing Fe and Zn ions, and MBP-DnaJ containing 2 Zn ions
      stimulated the ATPase activity of DnaK, prevented the aggregation of denatured
      rhodanase and bound to DNA to similar extents. On the other hand, metal-free MBP
      DnaJ showed much lower DNA-binding ability and lower ability to prevent rhodanese
      aggregation. Therefore, the bound metal species do not affect the function of the
      zinc finger-like motif of DnaJ, whereas removal of the metal ions from DnaJ
      diminishes its binding ability as to DNA and denatured proteins.

PMID- 9756633
TI  - Characterization and primary structure of a base non-specific and acid
      ribonuclease from Dictyostelium discoideum.
AB  - A base non-specific and acid RNase was isolated from cellular slime mold
      (Dictyostelium discoideum) cells in a homogeneous state (about 2.4 kDa) by SDS
      polyacrylamide gel electrophoresis. The RNase (RNase DdI) has a pH optimum of
      5.0. The amino acid sequence of RNase DdI was determined by a combination of
      protein chemistry, a search of Data base, Dicty cDB and further sequence analysis
      of cDNA from the same bank. RNase DdI consists of 198 amino acid residues, and
      about 13.3, 0.9, 1.2, 3.3, and 1.0 residues of mannose, xylose, glucose, GlcNAc,
      and GalNAc, respectively. RNase DdI has two characteristic conserved segments of
      the RNase T2 family, and thus belongs to the RNase T2 family. Considering the
      fact that most of the RNase activity of D. discoideum is present in the lysosomal
      fraction [Wiener and Ashworth (1970) Biochem. J. 118, 505-512], it was concluded
      that the lysosomal RNase in D. discoideum is a member of the RNase T2 family. The
      amino acid sequence of RNase DdI is highly homologous with that of Physarum
      polycephalum RNase (RNase Phyb), and its amino acid sequence seems to be similar
      to those of plant/animal type RNases, rather than fungal RNases. The location of
      RNase DdI in the phylogenetic tree of the RNase T2 family was estimated.

PMID- 9756634
TI  - Promotion of polypeptide folding by interactions with Asn-Glycans.
AB  - We have recently revealed that the intramolecular Asn-glycans promote the
      refolding of reductively denatured bovine pancreatic RNase B, and that
      extramolecular Asn-glycans of both high-mannose and complex types also markedly
      stimulate the oxidative refolding of RNase B and its nonglycosylated form, RNase
      A [Yamaguchi, H. and Uchida, M. (1996) J. Biochem. 120, 474-477; Nishimura et al.
      (1998) J. Biochem. 123, 516-520]. The present investigation was undertaken to see
      whether this function of Asn-glycans is specific to the refolding of pancreatic
      RNases; i.e., extramolecular Asn-glycans were examined for their effects on the
      oxidative refolding of hen egg white lysozyme and bovine alpha-lactalbumin by
      monitoring changes in activity, dynamic volume, intrinsic fluorescence, and
      affinity for a fluorescent probe, 1-anilino-8-naphthalenesulfonate. Asn-glycans
      of both high-mannose and complex types markedly stimulated the oxidative
      refolding of these proteins, giving similar results to those previously obtained
      with RNases, though differences attributable to the characteristics of individual
      proteins were observed in the promotive effects. Thus it seems probable that Asn
      glycans generally promote the proper folding of denatured polypeptides.

PMID- 9756635
TI  - Desensitization of human muscarinic acetylcholine receptor m2 subtypes is caused
      by their sequestration/internalization.
AB  - Desensitization of human muscarinic acetylcholine receptor m2 subtypes (hm2
      receptors) stably expressed in chinese hamster ovary cells was measured as
      decreases in the carbamylcholine-stimulated [35S]GTPgammaS binding activity in
      membrane preparations after pre-treatment of cells with carbamylcholine. The
      extent of carbamylcholine-stimulated [35S]GTPgammaS binding activity was found to
      decrease to 64% following pretreatment of cells with 10 microM carbamylcholine
      for 30 min, and under the same conditions 51-59% of hm2 receptors were
      sequestered/internalized as assessed by decreases in the [3H]N-methylscopolamine
      binding activity on the cell surface. A similar reduction in the carbamylcholine
      stimulated [35S]GTPgammaS binding activity was observed by pretreatment of cells
      with 5 nM propylbenzylylcholine mustard, which irreversibly bound to and
      inactivated 58% of the hm2 receptors. When the cells were pretreated with 10
      microM carbamylcholine in the presence of 0.32 M sucrose, which is known to
      inhibit clathrin-mediated endocytosis, no sequestration/internalization of hm2
      receptors was observed, and the extent of carbamylcholine-stimulated
      [35S]GTPgammaS binding activity did not change. These results indicate that
      desensitization of hm2 receptors may be caused by reduction of receptor number on
      the cell surface through sequestration/internalization rather than by loss of the
      function of receptors.

PMID- 9756636
TI  - Serum amine oxidase can specifically recognize and oxidize aminohexyl (AH) chains
      on AH-Sepharose support: single-step affinity immobilization.
AB  - Preparative affinity chromatography of bovine serum amine oxidase (SAO) on
      aminohexyl (AH)-Sepharose was often associated with an unexpected irreversible
      SAO retention on the support. This particular enzyme immobilization, occurring
      without coupling reagents, was supposed to be due to a SAO ability to: (i)
      recognize alkylamine groups of the support as macro-molecularized substrate; (ii)
      catalyse their oxidation to the corresponding aldehydes, with release of NH3 and
      H2O2; and (iii) be immobilized on the activated support by a coupling between the
      nascent aldehyde groups and SAO free amine groups. This affinity immobilization
      procedure, with the self-activation of the support, being mild, allows by simple
      incubation for 24 h, the enzyme immobilization with the retention of 80% from
      original specific activity of free SAO. Immobilized SAO on AH-Sepharose
      microcolumns, viewed as a continuous flow-system reactor, was able to catalyse
      benzylamine oxidation for several weeks.

PMID- 9756638
TI  - Multinucleated giant cell formation induced by IFN-gamma/IL-3 is associated with
      restriction of virulent Mycobacterium tuberculosis cell to cell invasion in human
      monocyte monolayers.
AB  - One of the hallmarks of an effective immune response against Mycobacterium
      tuberculosis is the formation of granulomas containing multinucleated giant
      cells. IFN-gamma and interleukin-3 (IL-3) promote Langhans-type multinucleated
      giant cell formation and have been identified in T cell clones reacting to M.
      tuberculosis antigens. The ability of human monocytes treated with IFN-gamma and
      IL-3 to limit the spread of M. tuberculosis in an in vitro infection assay was
      examined. Monocytes were incubated with control medium, IFN-gamma, TNF-alpha, and
      calcitriol, a combination permissive to M. tuberculosis growth, or IFN-gamma and
      IL-3 and infected with a low inoculum of M. tuberculosis (Erdman). IFN-gamma/IL-3
      treatment reduced M. tuberculosis CFU relative to both untreated and IFN
      gamma/TNF-alpha/calcitriol-treated monocytes. Specifically, CFU were reduced by
      79% at 14 days in the IFN-gamma/IL-3 treatment group relative to the IFN
      gamma/TNF-alpha/calcitriol treatment group, an effect that was not due to toxic
      monocyte metabolites. M. tuberculosis growth restriction by IFN-gamma/IL-3
      treated monocyte monolayers was associated with the development of Langhans-type
      multinucleated giant cells. At the light microscope level, dense growth of M.
      tuberculosis surrounded by a ring of nuclei localized to the center of individual
      cells. The intracellular location of M. tuberculosis was confirmed by electron
      microscopy. In contrast, monocyte monolayers treated with IFN-gamma/TNF
      alpha/calcitriol consisted of a syncitium of cells containing monocyte
      aggregates. Nonlocalized linear arrays of M. tuberculosis were observed to be
      growing throughout such aggregates. These results suggest that physical
      sequestration of M. tuberculosis by Langhans-type multinucleated giant cells may
      limit cell to cell spread of this pathogen, thereby restricting growth.

PMID- 9756637
TI  - Regulation of arachidonic acid release and prostaglandin E2 production in thymic
      epithelial cells by ATPgammaS and transforming growth factor-alpha.
AB  - The arachidonic acid metabolites produced by thymic epithelial cells play a
      pivotal role in thymocyte development. We have discovered that ATP and TGF-alpha
      regulate the arachidonic acid metabolism in TEA3A1 rat thymic epithelial cells by
      activating phospholipase A2 enzymatic activity. Our present study demonstrates
      that ATP and its nonhydrolyzable analog ATPgammaS stimulate both prostaglandin E2
      production and Ca2+ influx in TEA3A1 cells. The stimulation of prostaglandin E2
      production and Ca2+ influx by ATP is inhibited by pertussis toxin treatment,
      indicating that ATP mediates its effect by binding to a G-protein-coupled
      purinergic receptor. Treatment of cells with ATPgammaS and transforming growth
      factor-alpha results in a synergistic activation of phospholipase A2 and
      stimulation of prostaglandin E2 production. Results from experiments using an
      inhibitor of receptor-mediated Ca2+ influx indicate that the synergistic
      stimulation of prostaglandin E2 production by ATPgammaS and transforming growth
      factor-alpha requires ATPgammaS-mediated Ca2+ influx. The inhibitor of tyrosine
      kinase genistein also blocked both ATPgammaS- and ATPgammaS plus transforming
      growth factor-alpha-mediated stimulation of prostaglandin E2 production,
      indicating that the activation of phospholipase A2 may involve a protein tyrosine
      phosphorylation step.

PMID- 9756639
TI  - Control of endotoxin shock by the dried preparation of low virulent Streptococcus
      pyogenes OK-432.
AB  - Bacterial endotoxin, lipopolysaccharide (LPS), is a causative agent of Gram
      negative septic shock. However, if preadministered at a low dose, LPS makes mice
      resistant to subsequent endotoxin challenge, the phenomenon known as LPS
      tolerance. Here we demonstrated that the pharmaceutical preparation of Gram
      positive Streptococcus pyogenes, OK-432, also induced a state analogous to LPS
      tolerance if administered 6-48 h prior to LPS challenge. The preadministration of
      OK-432 increased the lethal dose of LPS threefold in BDF1 mice, and this was
      accompanied by reduced gene expression of IL-6, IFN-gamma, inducible nitric oxide
      synthase, and IL-10 in spleen and peritoneal cells. Serum concentrations of IL-6
      and IFN-gamma were also suppressed by the preadministration of OK-432. In
      contrast to the LPS tolerance, the levels of TNF-alpha mRNA were not suppressed
      in OK-432-administered mice, and their peritoneal cells produced high levels of
      TNF-alpha and soluble TNF receptor p75 in response to LPS in vitro. Peritoneal
      cells from OK-432 but not LPS-administered mice were hyporesponsive to IFN-gamma
      in terms of nitric oxide synthesis, and this hyporesponsiveness to IFN-gamma was
      abrogated by anti-IL-10 antibodies. Likewise, peritoneal cells from both OK-432-
      and LPS-administered mice were hyporesponsive to LPS, serum, TNF-alpha, IFN
      gamma, and PMA in terms of IL-6 production. Anti-IL-10 antibodies increased IL-6
      production eightfold in cells from OK-432-administered mice, but marginally in
      cells from LPS-administered mice. Even in peritoneal cells from OK-432
      administered mice, anti-IL-10 antibodies failed to fully restore IL-6 production.
      Thus, the hyporesponsive state of peritoneal cells was mediated by both IL-10
      dependent and -independent mechanisms. These results demonstrated that OK-432
      controlled endotoxin shock by blocking the cytokine cascade from TNF-alpha.

PMID- 9756640
TI  - Interleukin-12 is expressed by infiltrating macrophages and synovial lining cells
      in rheumatoid arthritis and osteoarthritis.
AB  - TH1 cytokines have recently been detected in rheumatoid arthritis (RA) and
      osteoarthritis (OA). For this reason we studied the TH-1-promoting cytokine IL-12
      in synovial membranes from patients with RA and OA. IL-12 transcripts and protein
      were analyzed by reverse transcriptase-polymerase chain reaction (PCR) and
      immunohistochemistry, respectively. In addition, IL-12 transcripts were
      quantitated by competitive PCR. IL-12 transcripts (p40) were detected in 8 of 13
      patients with RA and in 10 of 18 patients with OA. Their levels did not differ
      significantly between RA and OA. IL-12 heterodimer protein was detected by
      immunostaining using an anti-IL-12p70 mAb. Double labeling with anti-IL-12p70 and
      anti-CD68 mAbs showed that synovial lining cells and monocytes/macrophages
      expressed IL-12 p70 protein. The presence of IL-12 p70 protein in the synovial
      membranes of patients with RA and OA suggests that IL-12 may play an important
      immunoregulatory role in these diseases by perpetuating inflammation.

PMID- 9756641
TI  - The wst gene regulates multiple forms of thymocyte apoptosis.
AB  - Mice homozygous for the autosomal recessive mutation Wasted (wst/wst) display a
      disease characterized by immunodeficiency, cerebellar dysfunction, and
      sensitivity of their hematopoeitic cells to gamma radiation. Wasted mice die by
      30 days of age. In this report, we show that the Wasted thymus shows evidence of
      dramatically increased apoptosis in situ. Moreover, wst/wst thymocytes are more
      sensitive to apoptosis induced by gamma radiation, heat shock, alpha-CD3
      stimulation, and dexamethasone treatment in vitro. Thus, wst gene is a regulator
      of thymocyte apoptosis both in vitro and in vivo. The elevated levels of
      thymocyte apoptosis may be a major contributor to the lymphoid dysfunction and
      ultimate death in wst/wst mice.

PMID- 9756642
TI  - Acceleration of experimental autoimmune encephalomyelitis in interleukin-10
      deficient mice: roles of interleukin-10 in disease progression and recovery.
AB  - Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the
      central nervous system (CNS) which is often used as an animal model for human
      multiple sclerosis (MS). The disease is mediated by autoreactive lymphocytes
      recognizing myelin self-antigens. The autoreactive lymphocytes elicit autoimmune
      inflammation in the CNS and lead to demyelination and loss of neurological
      functions. Although autoimmune encephalomyelitis can lead to irreversible nervous
      tissue injury and demise of animals, EAE is often characterized by spontaneous
      disease recovery or remission. It is not known how EAE progression is regulated,
      nor is it clear how autoimmune inflammation in the CNS can resolve while the
      myelin-specific lymphocytes and myelin self-antigens remain in the animals.
      Cytokines, especially TH2-type cytokines, have long been suggested to play a role
      in regulating EAE. However, experiments using recombinant cytokines or
      neutralizing antibodies to cytokines have generated conflicting results. To
      determine the roles of interleukin (IL)-4 and IL-10 in experimental autoimmune
      encephalomyelitis, we have studied mice deficient in IL-4 or IL-10. We found that
      IL-10- but not IL-4-deficient mice had accelerated EAE following immunization
      with myelin oligodendrocyte glycoprotein (MOG). Importantly, spontaneous recovery
      from EAE occurred in normal and IL-4-deficient mice, but not in mice deficient in
      IL-10. Furthermore, we established that the acceleration of EAE in IL-10
      deficient mice was associated with a decrease in IL-4 and an increase in IFN
      gamma production in response to MOG antigen. These results strongly suggest that
      IL-10 plays a crucial role in the progression and recovery of autoimmune
      encephalomyelitis.

PMID- 9756643
TI  - Induction of T cell anergy by high concentrations of immunodominant native
      peptide is accompanied by IL-10 production and a block in JNK activity.
AB  - The ability to induce anergy in antigen-specific T cells has potential
      therapeutic value for altering pathologic immune responses. This study was
      undertaken to further analyze changes in cytokine production and intracellular
      signaling during anergy induction using high concentrations of native peptide
      ligand of tetanus toxoid (TT)- and myelin basic protein (MBP)-specific human T
      cell lines. The TT-selected T cell line could be rendered unresponsive to its
      dominant epitope in a dose-dependent manner (IC50 = 0.03 microg/ml). The TT
      selected line, as well as three T cell clones established from this line,
      continued to produce IFN-gamma and significantly increased IL-4 and IL-10
      production when anergy was induced with high concentrations of the immunodominant
      epitope. JNK enzymatic activity was blocked in anergized T cells. The MBP
      selected line could likewise be rendered unresponsive by incubation with
      supraoptimal concentrations of immunodominant peptide and anergy induction was
      accompanied by IL-10 release. Both T cell lines could be anergized by the
      autopresentation of native peptide since anergy was induced in cultures lacking
      fresh antigen-presenting cells. This study shows that the mitogen-activated
      protein kinase cascade is blocked when anergy is induced to high concentrations
      of soluble peptide.

PMID- 9756644
TI  - Membrane IgM-stimulated human B lymphocytes succumb to activation-related
      apoptosis at a G1-->S transition: influence of ligand affinity and valency.
AB  - Culture of human B lymphocytes with polyclonally activating surrogates for type
      II T-cell-independent antigen, i.e., anti-IgM mAb and anti-IgM:dextran, resulted
      in both membrane IgM (mIgM)-triggered S/G2/M entry and apoptosis. Although high
      ligand valency could compensate for low affinity, and high affinity could
      compensate for low valency, in achieving mIgM-triggered apoptosis, the phenomenon
      was most pronounced when the soluble "antigen" had both high binding site
      affinity and valency. Most of the mIgM-triggered apoptosis may represent B cells
      which progress into G1 but fail to receive a sufficient level of continuous mIgM
      mediated signaling during G1 for passage through a G1 --> S phase restriction
      point(s). This was supported by the findings that (a) a lesser proportion of mIg
      triggered cells enter S phase than G1; (b) maximal mIgM-triggered apoptosis was
      noted at 48-72 h of culture and surrounding activated cell clusters; (c) mIgM
      triggered apoptosis was not inhibited by pharmacologic blockers of S phase; and
      (d) a high proportion of viable mIgM-triggered B cell blasts in G1 succumb to
      apoptosis rather than enter S phase, if high-affinity multivalent ligand is
      washed from the cultures. In addition to quantitative aspects of initial receptor
      engagement, the potential for a protracted period of recurrent mIgM signaling
      events may influence whether apoptosis or cell cycle progression is the
      functional outcome of B cell encounter with a multivalent antigen.

PMID- 9756648
TI  - pH- and Thermo-sensitive Hydrogel Nanoparticles.
AB  - pH- and temperature-sensitive hydrogel nanoparticles of copolymers of
      vinylpyrrolidone (VP) and acrylic acid (AA) cross-linked with NN' methylene bis
      acrylamide (MBA) of sizes up to 50 nm diameter loaded with marker compound FITC
      dextran (mol wt. 19.3 kD) were prepared in the aqueous core of reverse micellar
      droplets and were dispersed in aqueous buffer. These particles have high
      entrapment efficiency, and the lyophilized powder can be redissolved in buffer
      without any significant agglomeration. The release of FITC-dextran from these
      particles was found to be pH- and temperature-dependent. The release was slow in
      acid solution, but it increased considerably as the pH of the medium was
      increased. The release rate was also increased with the increase of temperature.
      Copyright 1998 Academic Press.

PMID- 9756645
TI  - Decreased protein levels of the c-Cbl protooncogene in murine AIDS.
AB  - Murine acquired immunodeficiency syndrome (MAIDS) can be viewed as a
      lymphoproliferative disease which involves B cells as well as T cells from spleen
      and lymph nodes while thymus and Peyer's patches do not participate in the
      process. The 120-kDa protooncogene product c-Cbl was initially cloned from the
      murine Cas NS-1 B cell lymphoma. It is a main target of immunoreceptor (TCR and
      BCR)-mediated protein tyrosine kinase activity. Moreover, recent data suggest
      that c-Cbl might play a crucial role in the regulation of cell proliferation
      through regulation of GTP-binding proteins. Therefore, the involvement of c-Cbl
      was evaluated in the lymphoproliferative disease induced by the MAIDS virus. The
      expression of the c-Cbl protein was dramatically reduced in the lymph node of
      infected mice while it remained normal in the thymus. In contrast, the expression
      of actin, TCR-zeta chain, ZAP-70, and p59(fyn) remained similar in controls and
      infected mice. Identical results were obtained with sorted B cells and T cells.
      Surprisingly, a B cell lymphoma line derived from late stage MAIDS mice displayed
      a normal level of c-Cbl.

PMID- 9756649
TI  - Thermodynamics of Cationic Surfactant Sorption onto Natural Clinoptilolite.
AB  - Sorption enthalpies of hexadecyltrimethylammonium bromide (HDTMA) as monomers and
      micelles and tetraethylammonium bromide (TEA) were used with surfactant,
      counterion, and co-ion sorption isotherms to infer the conformation, sorption
      mechanism, and relative stability of the sorbed surfactants on natural
      clinoptilolite. The average value of the sorption enthalpy was -10.38 kJ/mol for
      monomers, -11.98 kJ/mol for micelles, and +3.03 kJ/mol for TEA. Sorption of
      monomers produced a lower sorption plateau than equivalent micelle sorption
      (maxima 145 mmol/kg, 225 mmol/kg). Analysis of the sorption data demonstrated a
      change in the sorption mechanism at the external cation exchange capacity (ECEC)
      of clinoptilolite. Sorption data from below and above the ECEC were fit to a
      simple polynomial model and the Gibbs free energy of sorption (DeltaG0m) and
      sorption entropies were calculated. Resultant values of DeltaG0m were -9.27 and 
      14.38 kJ/mol for HDTMA monomers and micelles, respectively, for sorption below
      the ECEC, and -16.11 and -23.10 kJ/mol, respectively, for sorption above the
      ECEC. The value for TEA was -1.04 kJ/mol, indicating weaker sorption than for
      HDTMA. Monomer sorption to clinoptilolite exceeded the ECEC, even when the
      solution concentration was below the critical micelle concentration. Hydrophobic
      (tail-tail) components of DeltaG0m were the driving force for sorption of HDTMA,
      both below and above the ECEC. A significant kinetic effect was observed in the
      sorption isotherms with a period of rapid sorption followed by slow equilibration
      requiring 7 days to achieve steady state for HDTMA; TEA equilibration occurred
      within 24 h. Copyright 1998 Academic Press.

PMID- 9756650
TI  - Dispersion Stability and Photo-activity of Rutile (TiO2) Powders.
AB  - The dispersion stability and photo-activity of rutile (TiO2) powders are
      reported. Factors influencing these properties, such as the pH values of the
      solutions used to treat the surfaces and the concentration of inorganic solids
      such as SiO2 and Al2O3 deposited onto the surfaces, are investigated. Si only on
      the surface of TiO2 gave rise to a poor coating efficiency, but a mixture of Al
      and Si improved it considerably. SiO2 precipitates onto the surface of rutile at
      a higher pH (9.04) than Al2O3 (7.9), and it can be assumed that, in cases where
      both are precipitated from one mixture, a layer of silica is first formed.
      Temperature seems to have a negligible effect on the coating efficiency of Al2O3
      if Al2(SO4)3 is used as a surface agent, but when NaAlO2 is used a non-linear
      correlation exists between temperature and coating efficiency, which is higher at
      291 K than at higher temperatures. TiO2 surfaces treated with SiO2 show a greater
      dispersion stability than those treated with Al2O3. In the cases of SiO2/Al2O3
      mixtures that were deposited onto the surfaces, the dispersion stability
      increased when the Si/Al ratios exceeded 0.6, although the absolute mass of Al2O3
      deposited also affects this stability. The influence of various organic reagents
      on the dispersion stability is reported. The photo-activity of the samples was
      determined by means of the degradation of methylene blue on the surface.
      Copyright 1998 Academic Press.

PMID- 9756651
TI  - New Methods for Studying Foams: Foaminess and Foam Stability.
AB  - New methods for studying the foaminess (the surface foam stability) and the foam
      stability (the internal structural foam stability) have been elaborated. The
      experimental technique and results are presented. Copyright 1998 Academic Press.

PMID- 9756652
TI  - Low-Frequency Dielectric Response of Polystyrene Latex Dispersions.
AB  - The low-frequency permittivity and the conductivity increments of a well
      characterized polystyrene sulfate latex with constant surface charge density were
      measured in KCl electrolyte solutions. The ionic strength was varied in the range
      0.4-6 mM. The data could be explained with one absolute surface-conductivity
      parameter over the complete concentration range. The titratable surface charge
      density correlates well with the surface conductivity, the ions in the double
      layer having the bulk mobility. The results are in good agreement with static
      conductivities of plugs composed of the same particles obtained in a previous
      study (1). The electrokinetic charge obtained from streaming potentials (1) in
      that study is significantly lower, confirming the presence of conduction behind
      the shear plane. In order to interpret the conductivity data, simple analytical
      expressions have been derived for the frequency-dependent complex conductivity of
      a dilute dispersion of spherical particles with relatively thin double layers
      (kappaa >>1, where a is the particle radius and kappa-1 the Debye screening
      length). The expressions are restricted to binary suspending electrolytes.
      However, no restrictions on the ion mobilities and ion valencies are made. Our
      results agree well with the numerical results of the dielectric model of
      Mangelsdorf and White (2, 3) and reduce to O'Brien's static conductivity results
      (4) in the limit of low frequencies. Copyright 1998 Academic Press.

PMID- 9756653
TI  - A New Methodology for Studying Protein Adsorption at Oil-Water Interfaces.
AB  - A new methodology has been developed for studying the adsorption behavior of
      proteins at oil-water interfaces. This technique employs the radiotracer method
      for monitoring adsorption of 14C-labeled proteins at the oil-water interface. The
      uniqueness of the new method lies in the formation of a 1000 A thick triglyceride
      oil film on the water surface. beta-casein was used to generate a standard curve
      for relating interfacial radioactivity (uCi/m2) to cpm at the oil-water
      interface. Adsorption isotherm of beta-casein was determined in the bulk protein
      concentration range 1.5 x 10(-5)-3.8 x 10(-3)% by weight of solution. The
      saturated monolayer coverage was found to be about 7.3 mg/m2. This value was
      quite different from other values reported in the literature. Adsorption studies
      with another protein, lysozyme, at the oil-water interface also revealed a high
      surface concentration of 3.0 mg/m2. The most significant difference between the
      adsorption of beta-casein at the oil-water and air-water interfaces was the lack
      of an induction period for the development of interfacial pressure in the former.
      This difference may be attributed to the attractive dispersion interaction
      between protein molecules and the oil phase. Copyright 1998 Academic Press.

PMID- 9756654
TI  - The Instability of Silica Sol in Concentrated Solutions of Triton X100.
AB  - An excess of nonionic surfactant, Triton X100, in the continuous phase of silica
      sol has strong consequences on the stability of silica dispersions. Beyond full
      coverage, the surfactant may give rise to the formation of either fractal or
      dense aggregates. The structure of aggregates has been studied through SAXS. It
      has been demonstrated that hydration of the components is an essential ingredient
      which influences the interparticle interactions. Some comparisons with current
      theoretical models developed for depletion flocculation are made. Copyright 1998
      Academic Press.

PMID- 9756655
TI  - Surfactant Effect on the Stability and Electrorheological Properties of
      Polyaniline Particle Suspension.
AB  - In this paper, the colloidal stability and electrorheological responses of semi
      conductive polyaniline particles dispersed in a mineral oil were investigated
      experimentally. The polyaniline was synthesized by polymerization of aniline
      monomer. The surfactants used for the colloidal stability were commercially
      available nonionic Span20, Span80, and Span85, which are distinctly different in
      their molecular structures. Dynamic yield stress of polyaniline suspension, which
      possessed the quadratic dependence on electric field strength at low electric
      field, exhibited the linear dependence at high electric field. In addition, the
      conductivity of polyaniline particles influenced the electrorheological response
      and there existed the optimal conductivity for the maximum yield stress. In the
      presence of nonionic surfactants used here, the yield stress of polyaniline
      exhibited a local maximum at a certain surfactant concentration. The existence of
      optimal surfactant concentration was confirmed by the surfactant adsorption
      isotherm. We hypothesized that below the optimal threshold concentration, the
      electrorheological activity was enhanced by the increased interfacial
      polarization induced by the adsorbed surfactant molecules. Above the threshold
      concentration, however, the electrorheological activity was degraded by the
      conduction through the field-induced surfactant-rich bridge between adjacent
      particles. This optimal concentration coincided with the saturation concentration
      in the adsorption isotherm. The surfactants used in this study showed the
      improved colloidal stability due mainly to the induced steric hindrance effect.
      For the colloidal stability, Span80 was the most effective. However, considering
      that ER activity comes mainly from relatively large particles of O(um), which are
      mostly present in our system, Span85 was the best choice for a stabilizing
      additive in the present ER suspension. In addition, our results showed that the
      presence of the nonionic surfactants considered here did not cause any sensible
      degradation at high temperatures. Copyright 1998 Academic Press.

PMID- 9756656
TI  - Formation and Properties of Lamellar Phases in Systems of Cationic Surfactants
      and Hydroxy-Naphthoate.
AB  - We investigated the phase behavior and the phase transitions in aqueous solutions
      of 100 mM cetyltrimethylammonium hydroxide (CTAOH) with 3-hydroxy-2-naphthoic
      acid (HNC) and of 100 mM cetyltrimethylammonium bromide (CTAB) with sodium-3
      hydroxy-2-naphthoate (SHNC). The naphthoate/surfactant ratio has been varied. As
      previously observed by the groups of C. Manohar and J. Candau we observed for the
      second system two viscoelastic gel-like regions, two liquid crystalline regions,
      and a precipitate region. For the CTAOH/HNC system one finds with increasing
      concentration of HNC a low viscous solution, a viscoelastic gel, and a
      viscoelastic liquid crystalline Lalpha-phase. In both surfactant systems the
      lamellar phase is formed around an equimolar ratio of cationic surfactant and
      naphthoate. The lamellar phases have been examined by polarization microscopy and
      freeze-fracture electron microscopy. The Lalpha-phase in the system CTAOH/HNC
      consists of densely packed multilamellar vesicles while the lamellar phase in the
      system CTAB/SHNC contains vesicles, as well as stacked bilayers and tubuli.
      Corresponding to their different microstructures the lamellar phases in the
      system, CTAOH/HNC and CTAB/SHNC have different rheological properties. The
      vesicular phase is highly viscoelastic and has a yield stress value while the
      bilayer phase has a much lower viscosity and no yield stress value. The
      transition from the micellar to the vesicle phase occurs for CTAOH/HNC over a two
      phase region, where micelles and vesicles coexist. In the case of CTAB/SHNC the
      transition from the micellar to the lamellar phase occurs over a three-phase
      region, where a surfactant-poor phase coexists with a lamellar and a coacervate
      phase. In mixtures of CTAB and SHNC a thick precipitate is formed at an equimolar
      ratio of CTAB and SHNC. This precipitate consists of condensed multilamellar
      vesicles that contain little water and stick together, as the vesicles collapse
      due to the shielding of the repulsive forces by NaBr from an unbinding to a
      binding state. The precipitate can be retransformed to a swollen lamellar phase
      by charging the vesicles with an excess of ionic surfactant, by adding
      electrolyte in high concentrations, or by increasing the temperature. As
      predicted by C. Manohar et al. the vesicle phases show a phase transition at a
      critical temperature Tc of 46 degreesC. This transition was detected by us for
      the first time by DSC and by conductivity measurements. It occurs within a narrow
      temperature range of 2-3 degrees with an enthalpy change of 0.5 kJ/mol. The
      transition is observed both in the swollen and in the precipitated vesicle phase.
      It is well separated from the vesicle/rod transition at higher temperatures (>70
      degreesC) and the liquid crystalline/crystalline transition at lower temperatures
      (25-30 degreesC) that has a melting enthalpy of 55 kJ/mol. It is conceivable that
      the observed transition at 46 degreesC is due to the melting of a two-dimensional
      solid-like lattice of the HNC-counterions on the vesicle interface. Copyright
      1998 Academic Press.

PMID- 9756657
TI  - Modified van der Waals Equation for the Prediction of Multicomponent Isotherms.
AB  - A modified two-dimensional van der Waals equation model was proposed for the
      prediction of multicomponent gas-solid adsorption isotherms from corresponding
      single-component adsorption equilibrium data. The model was used to predict
      adsorption isotherms of CO-CO2 mixtures and CO2-N2 mixtures on Cu(I)-NaY zeolite.
      Experimental adsorption equilibrium data of the two systems were compared with
      results calculated from the model and three other models in the literature: the
      ideal adsorbed solution model, the vacancy solution theory of adsorption using
      the Flory-Huggins activity coefficient equation, and the two-dimensional van der
      Waals equation. The results indicated that the modified van der Waals equation
      predicted the experimental results better than the three other models for the two
      systems studied, especially for the CO-CO2 system, which involved chemical
      reaction during adsorption and exhibited azeotropic behavior. Copyright 1998
      Academic Press.

PMID- 9756658
TI  - Simulation of Particle Adsorption onto a Polymer-Coated Surface Using the
      Dissipative Particle Dynamics Method.
AB  - Dissipative particle dynamics (DPD) was originated as a tool for performing fluid
      dynamics simulations of complex fluids and among other things has been used to
      simulate dilute polymer solutions. This report describes a new application of the
      technique-modeling the adsorption of colloidal particles onto a polymer-coated
      surface. This type of simulation would be beyond the scope of molecular dynamics
      but is effectively modeled with DPD. The preliminary results of these
      investigations, presented here, show good agreement with what might be predicted
      theoretically. They show that the colloidal particles would be less likely to
      adsorb onto the surface as the size of the polymer relative to the particle is
      increased, or similarly as the density of the polymers is increased. They also
      show that particle adsorption is reduced when the polymer is well solvated. They
      demonstrate how particles that have agglomerated with each other find it more
      difficult to penetrate a polymer barrier because of their greater size. Further
      investigation is required to understand the effects of temperature. Copyright
      1998 Academic Press.

PMID- 9756659
TI  - TM-AFM Threshold Analysis of Macromolecular Orientation: A Study of the
      Orientation of IgG and IgE on Mica Surfaces.
AB  - Adsorption and orientation properties of two different types of immunoglobulin
      molecules on derivatized and native mica surfaces were investigated using TM-AFM.
      The analyses included height measurements at two different pH values and a new
      technique, presented here as threshold analysis, which displays the outer mantle
      shape of an adsorbed protein. A major difference in preferential orientation is
      observed upon comparing the adsorption of the two proteins onto the different
      surfaces. The characteristics of both the adsorbed immunoglobulin and the surface
      are important for any preferential orientation of the adsorbed protein. Copyright
      1998 Academic Press.

PMID- 9756660
TI  - Part I: Experimental.
AB  - Perikinetic coagulation experiments are reported which were performed under 1g
      and ug conditions during a flight in a sounding rocket, for dispersions of
      polystyrene, quartz, and amorphous silica particles. Coagulation rates for
      dispersions of polystyrene, quartz, and amorphous silica are found to increase
      significantly under ug conditions compared to 1g conditions. Another set of
      experiments was performed at 1g, 2g, 4g, and 7g, with different densities of the
      continuous phase; also a mixture of two different polystyrene latices was used.
      The most pronounced effect of gravity on coagulation rate is found for
      dispersions with a small density difference, on going from 1g to 2g. In this
      regime a significant decrease in coagulation rates is observed. For the latex
      mixture at pronounced density differences, gravity-induced coagulation was
      observed; however, the aggregates formed did not have a lasting contact. The rate
      constant calculated under ug conditions approaches the theoretical value of von
      Smoluchowski. By means of a video analysis of the perikinetic coagulation
      process, the formation of doublets was studied. The "interaction time" for two
      particles was found to be longer for the density-matched dispersion. Doublets of
      particles are easily disrupted, and at 1g, free convection currents were observed
      even at small temperature differences in the system. Copyright 1998 Academic
      Press.

PMID- 9756661
TI  - Part II: Theoretical Analysis.
AB  - Three phenomena involved in the perikinetic coagulation process were studied with
      regard to their ability to account for the influence of gravity on the
      coagulation rate: (1) surface charge effects on the pressure in the gap between
      two approaching particles, through the streaming potential generated by the
      squeezing flow; (2) free convection induced by temperature changes in the
      surroundings; (3) surface roughness and hydration force effects on the
      interaction force between two particles. In a separate paper flow interactions
      between two identical spheres are shown to be insufficient to explain the
      influence of gravity on coagulation rate. Of these phenomena studied, a
      combination of surface roughness and free convection can explain the influence of
      gravity on coagulation. Copyright 1998 Academic Press.

PMID- 9756662
TI  - Structure of the Aggregates During the Process of Aggregation and Breakup Under a
      Shear Flow.
AB  - A particle size analyzer together with a video camera has been used to
      investigate the structure of the aggregates during the process of aggregation and
      breakup of particles in a shear flow induced by means of a Couette-flow system.
      Three different values for the shear rate have been used (25, 32, and 50 s-1).
      The initial volume fraction of the particles was phi0 = 5.0 x 10(-5). Different
      fractal dimensions (D3), D2, D1, and Dpf), the shape factor (xi2), and the aspect
      ratio (AR) have been used to characterize the structure of the aggregates. During
      the process of aggregation, no significant changes in the fractal dimensions,
      shape factor, and aspect ratio were found. The high values obtained for D3 (D3 =
      2.2) and D2 (D2) = 1.98) show us the high compactness of the flocs. Also, values
      of the fractal dimension and shape factor have been found to not depend on the
      shear rate. Copyright 1998 Academic Press.

PMID- 9756663
TI  - Influence of Size on Electrokinetic Behavior of Phosphatidylserine and
      Phosphatidylethanolamine Lipid Vesicles.
AB  - The aim of this study was to examine the electrokinetic properties of liposomes
      containing either phosphatidylethanolamine (PE) or phosphatidylserine (PS). Zeta
      potential was determined by laser-Doppler microelectrophoresis. The presence of
      PE enhanced the slight negative charge on the phosphate group of
      phosphatidylcholine. A linear relation between zeta potential and PE
      concentration was found. Absolute values of zeta potential were higher in PS
      liposomes and showed an exponential dependence on the PS content. The
      electrophoretic mobility depended not only on the percentage of aminophospholipid
      but also on the size of vesicles. This behavior can be explained by the
      relaxation effect. From geometrical considerations, it was possible to calculate
      the theoretical surface charge densities. Comparing experimental with theoretical
      values, an underestimation of zeta potential was found by the electrokinetic
      classic theory in the experimental conditions used. Copyright 1998 Academic
      Press.

PMID- 9756664
TI  - Anomalous Colloidal Stability of Latex-Protein Systems.
AB  - An experimental study on the colloidal stability of latex-F(ab')2 and latex-IgG
      systems is described. The stability domains were obtained using a low-angle
      scattering technique to measure the rates of aggregate formation and plotting the
      stability ratio as a function of electrolyte concentration. The protein-coated
      particles present an anomalous stability at high ionic strength when the
      classical theory predicts aggregation. This observed deviation from DLVO behavior
      appears for electrolyte concentrations above some critical bulk concentration
      called critical stabilization concentration (csc). As we have suggested in
      previous publications, the existence of an additional short-range repulsive
      "hydration force" can explain this anomalous stability. In order to resolve more
      fully if this anomalous stability at high ionic strength is due to the hydration
      forces, the effects of pH, cation and anion type, temperature, and polyethylene
      glycol (a dehydrating polymer) on the experimental stability are investigated.
      Finally, the immunoreactivity of an anti-CRP F(ab')2-latex conjugate is studied
      in reaction buffers with high ionic strength. Copyright 1998 Academic Press.

PMID- 9756665
TI  - Microcalorimetric Study of Argon, Nitrogen, and Carbon Monoxide Adsorption on
      Mesoporous Vycor Glass.
AB  - The adsorption of argon, nitrogen, and carbon monoxide in porous Vycor glass has
      been studied by volumetric and microcalorimetric methods and by thermoporometry.
      Samples with particle sizes ranging from <50 to >200 um have been selected and
      treated by sample controlled thermal analysis (SCTA). Subsequent characterization
      indicates that the particle size has no influence on the pore texture and nature.
      Thermal treatment, however, modifies the chemical nature of the surface. It would
      seem that nitrogen and carbon monoxide assume a distinct mean orientation leading
      to smaller effective cross-sectional areas than those usually accepted. Carbon
      monoxide clearly distinguishes two different types of adsorption site for samples
      treated at low temperature. Copyright 1998 Academic Press.

PMID- 9756666
TI  - Shear-Induced Flocculation of Colloidal Particles in Stirred Tanks.
AB  - Colloidal polystyrene and paramagnetic particles consisting of mixtures of
      polystyrene and magnetite are used to experimentally investigate flocculation
      kinetics in a stirred tank under turbulent shear flow. The effects of various
      parameters-agitation speed, solution pH, ionic strength, particle size, and
      particle concentration-on the flocculation rate are investigated. A trajectory
      model applicable for shear-flow systems is formulated to describe particle
      flocculation in stirred tanks. The collision efficiency of particles is obtained
      from the limiting trajectory of one particle moving toward another and is a
      function of interparticle forces and flow properties. The collision frequency is
      determined as a function of particle size and energy dissipation. The
      flocculation frequency is then determined by multiplying the collision frequency
      by the collision efficiency and is incorporated into a population balance model
      to predict the particle size evolution. Results suggest that the flocculation
      rate is enhanced by increasing the agitation speed, even though the collision
      efficiency is decreased at a higher agitation speed. It is also found that the
      collision rate increases and the collision efficiency decreases as the particle
      size ratio is increased. Results also suggest that the breakup rate of aggregates
      in a turbulent shear flow could be significant and may need to be included in the
      population balance modeling to correctly predict the evolution of particle size
      distribution. Copyright 1998 Academic Press.

PMID- 9756667
TI  - Analysis of Multicomponent Adsorption Close to a Dew Point.
AB  - We develop the potential theory of multicomponent adsorption close to a dew
      point. The approach is based on an asymptotic adsorption equation (AAE) which is
      valid in a vicinity of the dew point. By this equation the thickness of the
      liquid film is expressed through thermodynamic characteristics of the bulk phase.
      The AAE makes it possible to study adsorption in the regions of both the normal
      and the retrograde condensation. A simple correlation of the Kelvin radius for
      capillary condensation and the thickness of the adsorbed film is established.
      Numerical testing shows good agreement between the AAE and the direct
      calculations, even if the mixture is not close to a dew point. Copyright 1998
      Academic Press.

PMID- 9756668
TI  - Evaluation of the Structure and Acid-Base Properties of Bulk Wood by FT-Raman
      Spectroscopy.
AB  - The structure of pine wood (Pinus silvestris L.) has been analyzed by FT-Raman
      spectroscopy, taking birch wood and the wood components cellulose, hemicellulose
      (xylan), and lignin as well as previously characterized wood resins as
      references. The acid-base properties of bulk pine wood were evaluated by
      comparing the spectra recorded before and after the treatment with various
      solvents. After the treatment with the probe liquids having only a Lifshitz-van
      der Waals (LW) component, it was found that the LW interactions in pine wood take
      place without changing the main structure. After treatment with Lewis acid-base
      active probe liquids, the spectra indicate that, e.g., the intense peak located
      at approximately 2936 cm-1 (CH2 stretch) seems to disappear, suggesting that this
      peak may be related to Lewis acidity. In addition, after treatment with a Lewis
      acid, it was found that the intense peak located at approximately 1657 cm-1
      (C&dbond;C) is shifted, relating to Lewis basicity. With the ratio approximately
      2936/ approximately 1657 cm-1 as a measure of the acid-base properties of bulk
      wood, a value of about 2.00 indicates that the bulk pine wood is largely acidic.
      The pH determined supports the evaluation made by FT-Raman spectroscopy.
      Copyright 1998 Academic Press.

PMID- 9756669
TI  - Effect of Size Polydispersity on the Dielectric Relaxation of Colloidal
      Suspensions: A Numerical Study in the Frequency and Time Domains.
AB  - In this article, a systematic numerical study is described of the effect of the
      polydispersity of suspensions of spherical particles on their dielectric
      behavior, in both the frequency and time domains, starting from the model
      proposed by DeLacey and White (J. Chem. Soc., Faraday Trans. 2 77, 2007 (1981))
      for monodisperse suspensions. The distribution function of relaxation times,
      characterizing the dielectric response of the systems, is also calculated. It is
      found that in both the frequency and time domains the predicted behavior does not
      differ in any essential way from the one obtained for a monodisperse suspension
      with particle radius close to the volume-averaged mean radius of the polydisperse
      system. Hence, no arguments related to polydispersity seem to be useful for
      explaining the discrepancies frequently found between measured and calculated
      dielectric increments in suspensions, namely, those concerning the magnitude of
      the dielectric constant of the suspension (its low-frequency value), the value of
      the characteristic or relaxation frequency, or the overall shape of the
      relaxation pattern. Copyright 1998 Academic Press.

PMID- 9756670
TI  - SAXS Study on Gelation Process in Preparation of Resorcinol-Formaldehyde Aerogel.
AB  - RF aerogels were prepared by sol-gel polycondensation of resorcinol with
      formaldehyde in a slightly basic aqueous solution and supercritical drying with
      carbon dioxide. The aerogels were characterized by nitrogen adsorption and
      density measurements. A small-angle X-ray scattering (SAXS) technique was applied
      to the gelation process of RF hydrogels. The structure formation of the hydrogels
      during the sol-gel transition was revealed by applying Guinier and power-law
      equations to the SAXS data. At the initial stage of the synthesis of RF
      hydrogels, small clusters of ca 2 nm consisting of branched polymeric species
      formed, showing a mass fractal dimension. Then the clusters aggregated and formed
      particles of ca 3-6 nm. These particles showed a surface fractal dimension. The
      hydrogel structure was fixed by gelation and the particles grew to ca 4-7 nm.
      Finally their surface became smooth by aging. The influence of the amount of
      resorcinol, basic catalyst, and water used in the polycondensation on the porous
      structures of the aerogels was explained by the structure formation model
      proposed. Copyright 1998 Academic Press.

PMID- 9756671
TI  - Precipitation of Barium and Calcium Naproxenate Particles of Different
      Morphologies.
AB  - Barium and calcium salts of naproxen, (+)-6-methoxy-alpha-methyl 2
      naphtaleneacetic acid, were prepared by the controlled double jet precipitation
      technique in the absence and in the presence of different surfactants. The nature
      of the latter and agitation used in the precipitation process were critical
      factors in determining the morphology and the size of the particles obtained,
      consisting, as a rule, of aggregates of much smaller subunits, which were either
      platelet or fiber like. Copyright 1998 Academic Press.

PMID- 9756672
TI  - Kinetic-Diffusion-Controlled Adsorption and Desorption Kinetics on Planar
      Surfaces.
AB  - The adsorption and desorption kinetics of water-soluble associative polymers with
      different molecular weights on the silicon wafers were studied by ellipsometry.
      The parameters characterizing the adsorption and desorption processes such as (a)
      the maximum amount of adsorbate adsorbed, Gammainfinity, (b) the equilibrium
      constant, K(p), (c) the activation energy of adsorption, (-DeltaH), (d) the rate
      constants for adsorption and desorption processes, Kad, Kdes, (e) the coefficient
      of diffusion, D0, (f) the activation energy of the effective diffusion, Q, and
      (g) the time needed to attain the equilibrium states for the adsorption and
      desorption processes were calculated from the experimental ellipsometric data. It
      is shown that the adsorption kinetics for mixtures over a wide range of
      concentrations is governed by: (I) the kinetic adsorption at the interface, (II)
      the kinetic adsorption at the interfaces as well as simultaneous diffusion,
      and/or (III) diffusion. The existence of regimes (I), (II), and (III) for
      adsorption and desorption kinetics are justified by using the experimental data
      for the adsorption and desorption kinetics of water-soluble associative polymers
      with different molecular weights of 12, 62, and 120 kg/mol. Copyright 1998
      Academic Press.

PMID- 9756673
TI  - An Adsorption Equation for an Ultrathin Fluid Film.
AB  - Henry's law is found by applying the condition of extremum to the Gibbs function
      of a fluid film. The resulting equation relates linearly the thickness of the
      adsorbed layer to the external gas pressure. The equation reveals that the
      coefficient of proportionality beta depends inversely on the saturation pressure
      p0. It also shows that wetting effects are irrelevant. These results predicted by
      the present model are in agreement with experiment. Copyright 1998 Academic
      Press.

PMID- 9756674
TI  - Diffusion in a Fractal System.
AB  - The surface geometry of Vycor porous glass was examined by using the relative
      permeability (PR) technique in a H2O/He system. At a water relative pressure of
      approximately 0.3, a maximum is observed on the PR curve. This maximum is
      explained in terms of geometrical changes taking place due to the deposition of a
      water film on the internal Vycor surface. When the sample is dry, diffusion in a
      fractal system is found to be more appropriate in describing the process. When
      the sample is wet, the diffusion process obeys classical Knudsen theory for
      smooth cylinders. Copyright 1998 Academic Press.

PMID- 9756675
TI  - Low-level prenatal lead exposure and neurobehavioral development of children in
      the first year of life: a prospective study in Shanghai.
AB  - We used a prospective study design to assess the effects of prenatal low-level
      lead exposure on the development of urban, inner-city children in Shanghai.
      Umbilical cord blood samples wee consecutively collected from 605 live newborns.
      Two hundred and fifty-seven samples were excluded from the study due to clotting.
      Lead levels were determined on 348 cord blood samples. The geometric mean was 9.2
      micrograms/dl. Based on their cord blood lead levels, infants were classified
      into two exposure groups: 104 in a relatively low lead group (lead levels < or =
      30 percentile), and 104 in a relatively high lead group (lead levels > or = 70
      percentile). Seventy-five subjects failed to complete the study, and 133 babies
      were included in the final cohort: 69 babies in the high lead group and 64 in the
      low lead group. At 3, 6, and 12 months, the Bayley Scales of Infant Development
      were administered and capillary blood lead levels were measured. Detailed
      information was obtained on a wide range of variables relevant to infant
      development. At all three ages, the Mental Development index (MDI) scores,
      adjusted for confounders, were inversely related to the infants' cord blood lead
      levels. The difference of the mean adjusted MDI scores between low and high lead
      groups was 3.4 at 3 months, 6.3 at 6 months, and 5.2 at 12 months of age. These
      differences were statistically significant at all time points. No significant
      association between cord blood lead levels and the Psychomotor Development Index
      (PDI) scores was detected at all three visits after adjustment for confounders.
      Postnatal lead levels were unrelated to concurrent developmental status. We
      conclude that prenatal low-level lead exposure, which is relatively common in
      Shanghai, is associated with an adverse developmental impact on children through
      the first year of life.

PMID- 9756676
TI  - Medical costs and lost productivity from health conditions at volatile organic
      compound-contaminated superfund sites.
AB  - This paper estimates the health costs at Superfund sites for conditions
      associated with volatile organic compounds (VOCs) in drinking water. Health
      conditions were identified from published literature and registry information as
      occurring at excess rates in VOC-exposed populations. These health conditions
      were: (1) some categories of birth defects, (2) urinary tract disorders, (3)
      diabetes, (4) eczema and skin conditions, (5) anemia, (6) speech and hearing
      impairments in children under 10 years of age, and (7) stroke. Excess rates were
      used to estimate the excess number of cases occurring among the total population
      living within one-half mile of 258 Superfund sites. These sites had evidence of
      completed human exposure pathways for VOCs in drinking water. For each type of
      medical condition, an individual's expected medical costs, long-term care costs,
      and lost work time due to illness or premature mortality were estimated. Costs
      were calculated to be approximately $330 million per year, in the absence of any
      remediation or public health intervention programs. The results indicate the
      general magnitude of the economic burden associated with a limited number of
      contaminants at a portion of all Superfund sites, thus suggesting that the burden
      would be greater than that estimated in this study if all contaminants at all
      Superfund sites could be taken into account.

PMID- 9756678
TI  - Uptake of HgCl2 and MeHgCl in an insect cell line (Aedes albopictus C6/36).
AB  - We studied the uptake mechanism of mercuric chloride (Hg) and methylmercuric
      chloride (MeHg) in Aedes albopictus C6/36 cells. The uptake kinetics, together
      with the effect of temperature and a metabolic inhibitor (2, 4-dinitrophenol) on
      the mercury accumulation, were examined. Both amounts of internalized Hg and MeHg
      increased linearly with the extracellular concentration. Initially, the influx
      rate was high for both metal species but MeHg was found to accumulate seven times
      faster than Hg. At longer exposure times it leveled off for Hg, while for MeHg,
      the intracellular concentration decreased. Hg toxicity was not significantly
      influenced by elevated temperatures; in contrast there was a marked decrease of
      the LC50/24h value for MeHg. On the other hand, Hg accumulation was temperature
      dependent but MeHg was not. The different toxicity and uptake rate of both
      mercury compounds can be explained in terms of membrane permeability and target
      site. For Hg the main target seems to be the plasma membrane, while MeHg readily
      crosses this barrier and reacts with intracellular targets. 2, 4-Dinitrophenol
      had no effect on the accumulation of Hg but that of MeHg was doubled. This
      increased MeHg accumulation might be the result of the inhibition of an active
      MeHg efflux mechanism; this is in agreement with the MeHg influx kinetics.
      Despite these differences between Hg and MeHg, which probably result from their
      physicochemical properties, our experiments indicate that, for both mercury
      species, simple diffusion is probably the main way to entrance in Aedes cells.

PMID- 9756677
TI  - Neurotoxic effects of low-level methylmercury contamination in the Amazonian
      Basin.
AB  - Many studies have demonstrated mercury contamination in the Amazonian ecosystem,
      particularly in fish, a dietary mainstay of populations in this region. The
      present study focused on potential health effects of this low-level methylmercury
      exposure. The study was carried out in a village on the Tapajos River, a
      tributary of the Amazon, on 91 adults inhabitants (15-81 years), whose hair
      mercury levels were inferior to 50 mu/g. Performance on a neurofunctional test
      battery and clinical manifestations of nervous system dysfunction were examined
      in relation to hair mercury concentrations. Near visual contrast sensitivity and
      manual dexterity, adjusted for age, decreased significantly with hair mercury
      levels (P < 0.05), while there was a tendency for muscular fatigue to increase
      and muscular strength to decrease in women. For the most part, clinical
      examinations were normal, however, hair mercury levels were significantly higher
      (P < 0.05) for persons who presented disorganized movements on an alternating
      movement task and for persons with restricted visual fields. These results
      suggest dose-dependent nervous system alterations at hair mercury levels below 50
      micrograms/g, previously considered a threshold for clinical effects. The profile
      of dysfunction in this adult population is consistent with the current knowledge
      on methyl-mercury poisoning. The long-term implications of these findings are
      unknown and need to be addressed.

PMID- 9756679
TI  - The impact of low technology lead hazard reduction activities among children with
      mildly elevated blood lead levels.
AB  - This prospective environmental intervention study was conducted to determine the
      impact of low-technology lead hazard reduction activities among children with
      mildly elevated blood lead levels. Children whose homes had severe lead hazards
      were automatically assigned to the intervention group. Children whose homes had
      lesser hazards were randomly assigned to the intervention group or comparison
      group. The one-time intervention focused mainly on cleaning and repainting window
      areas and educating caregivers to maintain effective housekeeping techniques.
      Changes in blood lead and dust lead loading levels were observed following the
      interventions. Analysis of covariance was used to adjust comparisons of
      postintervention levels for preintervention levels and other variables. The lead
      hazard reduction activities were associated with a modest decline in blood lead
      levels among children with severe hazards. The magnitude of the decline depended
      on the confounder that was controlled; the majority ranged from-1.1. to-1.6
      microgram/dL. A moderate reduction in window well dust lead loading levels was
      also observed. While low-technology lead hazard reduction measures appeared to be
      an effective secondary prevention strategy among children with severe household
      lead hazards, larger studies are needed to confirm these results.

PMID- 9756681
TI  - Handling and Disposal of Chemical Products/Management of Hospital Waste
      Substances and Residues.

PMID- 9756680
TI  - The contribution of lead-contaminated house dust and residential soil to
      children's blood lead levels. A pooled analysis of 12 epidemiologic studies.
AB  - In 1992, the U.S. Congress passed the Residential Lead-Based Paint Hazard
      Reduction Act, which requires the promulgation of health-based dust lead and soil
      lead standards for residential dwellings to prevent undue lead exposure in
      children. Unfortunately, the levels of lead in house dust and soil that are
      associated with elevated blood lead levels among U.S. children remain poorly
      defined. This pooled analysis was done to estimate the contributions of lead
      contaminated house dust and soil to children's blood lead levels. The results of
      this pooled analysis, the most comprehensive existing epidemiologic analysis of
      childhood lead exposure, confirm that lead-contaminated house dust is the major
      source of lead exposure for children. These analyses further demonstrate that a
      strong relationship between interior dust lead loading and children's blood lead
      levels persists at dust lead levels considerably below the U.S. Department of
      Housing and Urban Development's current postabatement standards and the
      Environmental Protection Agency's guidance levels. Finally, these analyses
      demonstrate that a child's age, race, mouthing behaviors, and study-site specific
      factors influence the predicted blood lead level at a given level of exposure.
      These data can be used to estimate the potential health impact of alternative
      health-based lead standards for residential sources of lead exposure.

PMID- 9756682
TI  - Editorial 

PMID- 9756683
TI  - Small mammal populations and community under conditions of extremely high
      thallium contamination in the environment.
AB  - Studies were carried out in the vicinity of a zinc smelter in southern Poland, 50
      km northwest of Krakow, where the previous measurements with another
      bioindication method revealed huge thallium levels in the environment. The
      mammals (106 individuals in total) were captured in four wooded areas situated
      1.5 to 2.5 km in various directions from the plant and in two reference sites,
      located far from industrial emission sources. Very high Tl levels were found in
      livers and kidneys of all mammals examined from the two areas nearest the
      smelter. Bank voles were the most loaded (maximum Tl in kidneys, 34.27
      microgram/g dry mass; in livers, 14.53 microgram/g; values from unpolluted areas
      were below the detection limit, 0.07 microgram/g). A distinct decrease in the
      amount of hair-a characteristic of thallium poisoning-was observed in several
      individuals. The extreme case was a wood mouse with the rear half of its body
      almost entirely hairless (!). Densities of single populations and the whole
      community were very low, up to 4.8 individuals/ha, including insectivores.
      Numerical proportions between species were changed in comparison to unpolluted
      areas. The age structure was deformed, with a disproportionate small
      participation by young generations. Among the males studied, only sexually
      inactive individuals were found. The condition of populations and the community
      of small mammals living here was much worse compared with data from the
      surroundings of other zinc smelters.

PMID- 9756684
TI  - Effect of heavy metals and storage time on two types of forest litter: basal
      respiration rate and exchangeable metals.
AB  - Two types of forest litter, MOR and MULL, were treated with 0 (control), 25, 100,
      400, 1600, and 6400 mg kg-1 Cd, Cu, Pb, or Zn after different storage times (35,
      75, and 125 days at approx 5 degreesC). Highly significant effects on respiration
      rate were observed for dose of heavy metals, type of litter, type of metal, and
      storage time. The respiration rate of untreated MULL litter was lower than that
      of untreated MOR in all incubations, and the slope of the relation to the dose of
      metals was steeper for MOR. Respiration rates after storage were lower than in
      fresh litter, and the slope of the relation between respiration rate and metal
      dose was less steep after storage. In the first incubation, MULL litter was more
      sensitive to Cd, Cu, and Pb and less sensitive to Zn than MOR litter. After 125
      days of storage, no single significant effect was found in MULL litter, whereas
      in MOR litter all metals still inhibited respiration rate significantly. The
      relative toxicity of metals was similar for both litter types, and the average
      EC50respiration values were (mg kg-1) Cu=3880, Zn=5610, Cd=6320, and Pb=24800.
      The percentages of exchangeable metals (1 M NH4OAc, pH=7) in MULL litter were
      lower on average than in MOR litter, and the order of solubility of the metals
      was Cd>Zn>Pb>Cu. Storage caused no significant difference in the average
      percentage of exchangeable metal. The highest doses of heavy metals increased the
      amounts of Ca, K, Mg, and Na extracted.

PMID- 9756685
TI  - Impact assessment of a wastewater treatment plant effluent using the fish
      biomarker ethoxyresorufin-O-deethylase: field and on-site experiments.
AB  - The impact of a wastewater treatment plant (WWTP) effluent was assessed with the
      fish biomarker ethoxyresorufin-O-deethylase (EROD) using field and on-site
      laboratory experiments. EROD activity was measured in chub (Leuciscus cephalus)
      and stone loach (Noemacheilus barbatulus) caught at three sites of the Chalaronne
      River (southeast France). Liver somatic index (LSI) and organochloride
      bioaccumulation in muscle were estimated for chub only. In September, EROD
      activity and LSI of chub increased significantly between the sites above and
      below the WWTP effluent discharge. EROD induction detected in chub was confirmed
      by on-site tank experiments. EROD levels were determined in juvenile rainbow
      trout (Oncorhynchus mykiss) and mirror carp (Cyprinus carpio) exposed to
      different concentrations of the WWTP effluent and river water for 16 days. After
      a 4-day exposure, EROD activities of the carp exposed to the effluent increased
      significantly compared with the control. The response was linked to the effluent
      concentration and was stable with exposure time. WWTP effluent induced EROD
      activity, whereas organic and metal analyses, performed on fish muscle and
      sediment, did not indicate any difference between upstream and downstream of the
      discharge.

PMID- 9756686
TI  - Sublethal effects of repeated intraperitoneal cadmium injections on rainbow trout
      (Oncorhynchus mykiss).
AB  - Acute and chronic effects of cadmium have been widely described for different
      aquatic organisms and exposure routes. However, there is clearly a lack of
      information on the potential of cadmium to cause genotoxic effects. This work
      presents genotoxic and nongenotoxic parameters analyzed in cadmium-exposed
      rainbow trout. The assessment was performed for sublethal levels after long-term
      exposure using six intraperitoneal injections of 0.5 mg/kg (Day 1), 1 mg/kg (Days
      3, 7 and 11), and 2 mg/kg (Days 15 and 19) to allow precise estimation of the
      dose. Cadmium accumulation in target tissues, essential metal mobilization by
      cadmium at the subcellular and tissue levels, and induction of metallothioneins
      were selected as exposure and effect parameters. Induction of micronuclei and
      variation in DNA content (expressed as variation coefficient in the G1 phase of
      the cell cycle) in blood cells, determined by flow cytometry, were selected as
      biomarkers for genotoxic effects. Cadmium accumulation, induction of
      metallothioneins, and mobilization of essential metals at the subcellular level
      were observed in different organs in response to cadmium exposure. The highest
      metallothionein induction was observed in liver, reaching 270+/-90 nmol/g wet
      tissue in treated fish versus 2.68+/-1.1 nmol/g wet tissue in controls. The
      highest cadmium accumulation was also observed in the liver (27.8+/-9.5 microgram
      Cd/g wet wt in treated animals versus 1.0+/-1.7 in the control group). However,
      no genotoxic effects were observed in blood cells. The frequency of micronuclei
      was 0.012+/-0.008 for the control group and 0.013+/-0.021 for treated animals.
      The variation coefficient of G1-phase nuclei was 3.61+/-0.66 and 3.22+/-0.29 for
      control and cadmium-exposed groups, respectively. Thus, it is concluded that
      under the experimental conditions employed here, treatment of rainbow trout with
      cadmium chloride at doses that produce significant toxicological alterations at
      the tissue and subcellular levels does not provoke observable alterations in the
      genotoxic parameters considered in this study.

PMID- 9756687
TI  - OH radical reactivity of pesticides adsorbed on aerosol materials: first results
      of experiments with filter samples.
AB  - Preliminary results of a new method to investigate the OH radical reactivity of
      semi-volatile organic compounds (e.g., pesticides) are presented. Terbuthylazine,
      simazine, sodium benzoate, and bromoxynil were adsorbed on highly disperse
      silicon dioxide powder as an unreactive carrier at a thickness well below one
      monolayer. The coated material was suspended in air as an aerosol, sampled on
      filters, and exposed in an 840-liter Duran chamber to OH radicals, produced by
      photolysis of hydrogen peroxide in the gas phase. Sunlamps on top of the chamber
      were used as cold light sources [T(aerosol) approximately 25 degreesC]. OH
      radical concentrations (10(5)<cOH (cm-3)<3x10(6)) were monitored in the gas phase
      using a set of four hydrocarbons with well-known OH reactivities as reference
      compounds. The triazine terbuthylazine (kOH=1.1x10(-11) cm3 s-1) was used as a
      reference compound in the filter samples. Simazine and isoproturon were found to
      react with a comparable OH rate constant with respect to terbuthylazine. Sodium
      benzoate reacts about a factor of 3 slower. Rapid degradation was observed for
      bromoxynil, explained mainly by photolysis. Besides the characterization and
      discussion of the experimental setup used, the rate constants obtained are
      discussed and compared with estimated values.

PMID- 9756688
TI  - Abiotic degradation of halobenzonitriles: investigation of the photolysis in
      solution.
AB  - This paper presents first experiments of laboratory investigations of the
      photodegradation by direct photolysis (lambda>290 nm) of cholorotahlonil,
      dichlobenil, chloroxynil, bromoxynil, and ioxynil in aqueous, pH-buffered, and
      organic solutions and the calculation of the quantum yields. The photolysis of
      chlorothalonil in water is low, with a corresponding low quantum yield
      (Phi=0.0001). Dichlobenil is photostable under the laboratory conditions used.
      The photoreactivity of bromoxynil and ioxynil was found to be comparable in
      aqueous solutions and about three times lower with respect to chloroxynil. The
      quantum yields obtained in water of chloroxynil, bromoxynil, and ioxynil are
      Phi=0.0060, 0.0093, and 0.0024, respectively. Half-lives of the pesticides in the
      environment with respect to direct irradiation are estimated using UV spectra and
      quantum yields as input variables obtained in the laboratory.

PMID- 9756689
TI  - Detection of DNA strand breaks in isolated mussel (Mytilus edulis L. ) digestive
      gland cells using the "Comet" assay.
AB  - Isolated mussel (Mytilus edulis L.) digestive gland cells were analyzed using the
      single-cell gel electrophoresis or "comet" assay to assess the ability of
      potential aquatic contaminants to induce DNA strand breaks (SBs) and to
      investigate the potential application of this technique as part of an aquatic
      biomonitoring regime. Freshly prepared cell suspensions from digestive gland were
      exposed in vitro to hydrogen peroxide (H2O2, 0-200 microM), 3-chloro-4
      (dichloromethyl)-5-hydroxy-2[5H]-furanone (MX, 0-200 microM), benzo[a]pyrene
      (BaP, 0-200 microM), 1-nitropyrene (1-NP, 0-250 microM) and nitrofurantoin (NF, 0
      1000 microM) for 1 h in the dark at 15 degreesC in the presence of the DNA repair
      inhibitor cytosine-beta-D-arabinofuranoside (araC). DNA strand breakage was
      measured using the comet assay. There were significant concentration-dependent
      increases in the percentage of DNA in the comet tail (mean values+/-SD) for all
      doses compared with controls (P<0.05) with H2O2 (up to 61.4+/-5.1% at 100
      microM), MX (up to 34. 3+/-2.2% at 200 microM), BaP (up to 24.7+/-5.1 at 100
      microM), 1-NP (up to 54.7+/-5.0% at 200 microM), and NF (up to 68.1+/-4.5% at 500
      microM). There was a decrease (P<0.05) in viability (eosin Y exclusion) of
      exposed compared with control cells at 200 microM H2O2 and BaP only. This study
      has demonstrated the potential of the comet assay to detect DNA strand breakage
      at subcytotoxic concentrations of a range of agents, some of which require
      metabolic activation. This may provide a sensitive, but nonspecific, molecular
      biomarker of genotoxicity.

PMID- 9756690
TI  - Ecotoxicological assessment of ashes and particulate matter from fluidized bed
      combustion of coal.
AB  - Toxicity of ash and particulate matter from the gases generated in coal fluidized
      bed combustion (FBC) has been determined by the Microtox assay according to the
      standard leachate procedure. Results are compared with the polycylic aromatic
      hydrocarbon (PAH) content of the particulate matter, which was determined by
      fluorescence spectroscopy. Although PAHs are considered highly toxic compounds,
      the low ecotoxicity values obtained could be explained by the low solubility of
      the compounds in water. The Microtox assay may underestimate the toxicity of
      water-insoluble compounds unless they are previously extracted with an organic
      solvent. Nevertheless, this type of assay can be very useful for measuring the
      potential toxicity of residues when exposed to water sources such as rain water
      and the risk of the components being dissolved and transported by runoff water.

PMID- 9756691
TI  - Memory effects in the action of ozone on conifers.
AB  - Conifers are known to possess relative ozone tolerance in short-term experiments.
      A scenario for ozone damage of conifers is now derived from the first exposure
      experiments in which both the initial biochemical response phase and delayed
      visible symptom development were studied. A number of early biochemical ozone
      responses could be detected in Norway spruce (Picea abies [L.] Karst.) and Scots
      pine (Pinus sylvestris L.). The stress metabolite catechin persisted over several
      months. In the year following ozone treatment of spruce, decreases in pigment
      content and photosynthetic capacity, as well as development of visible symptoms
      (chlorosis, banding), were determined in the needle age classes previously
      exposed to an accumulated hourly ozone dose above 40 ppb (AOT40) of >/=60-80 ppm
      small middle doth. The visible symptoms developed during spring emergence of the
      new flush. In the case of Scots pine, an ozone dose (AOT40) of >/=30 ppm small
      middle doth caused the premature shedding of needles 9 months after treatment.
      The delayed symptoms of both spruce and pine occurred during known phases of
      endogenous stress. The symptoms appeared to reflect an ozone "memory" imprinted
      by the induced early stress reactions. Ambient AOT40 ozone doses in Central
      Europe are in the range 4 and 50 ppm small middle doth per growing season. Ozone
      is proposed to potentially damage conifers through memory effects ("abiotic"
      pathway) or through predisposition for pathogen attack ("biotic" pathway).

PMID- 9756692
TI  - Influence of an aquatic humic acid on the bioconcentration of selected compounds
      in Daphnia magna.
AB  - Several chemicals covering a wide range of octanol-water partition coefficients
      were assayed for their bioconcentration in Daphnia magna in the presence of an
      aquatic humic acid. Assuming the properties of the humic acid used were similar
      to those known for organic matter from soils, the influence of the aquatic humic
      acid on physicochemical moderation of bioconcentration could not be demonstrated
      experimentally in a log Kow range of the chemicals between 2 and 6. Thus, the
      lipophilic character of the aquatic humic acid and the related effect of
      solubilization of the chemicals in the aqueous phase are much less than expected.
      This result is confirmed by determining the octanol-water partition coefficient
      of the aquatic humic acid. Comparing this value with log Kow values of humic
      acids of terrestrial origin, it can be clearly demonstrated that the
      lipophilicity of the aquatic humic acid is lower by a factor of 50.

PMID- 9756693
TI  - Establishment of a simple cleanup procedure and bioassay for determining 2,3,7,8
      tetrachlorodibenzo-p-dioxin toxicity equivalents of environmental samples.
AB  - The study was aimed at establishing a bioassay for the determination of 2,3,7,8
      tetrachlorodibenzo-p-dioxin toxicity equivalents (TEQs) in environmental samples.
      Specifically, development of a rapid cleanup procedure adapted to the needs of
      the bioassay and simplification of the measurement of its endpoint, the induction
      of 7-ethoxyresorufin O-deethylase (EROD) in rat H4IIEC3/T hepatoma cells, were
      desired. The results indicate that a single "sandwich" column suffices to remove
      substances that may interfere with the bioassay from extracts of various
      environmental matrices such as sewage sludge, compost, soil, sediment, fly ash,
      tissue filter dust, and fire residue. The cumbersome conventional in vitro assay
      for EROD activity on cells exposed to the test material in culture plates could
      readily be replaced by a simple assay on intact cells grown and treated in 96
      well microtiter plates. TEQ values obtained from the bioassays were consistently
      higher than those derived from chemical analysis of dibenzo-p-dioxins/furans and
      biphenyls by a factor of 1.5-3.0 depending on the matrix used. The results
      indicate that this bioassay, which combines a simple cleanup and a rapid
      procedure for measuring biological effects, offers a cost- and time-effective
      alternative to chemical analysis when screening large numbers of samples from
      complex environmental matrices.

PMID- 9756694
TI  - Role of algae in fate of carcinogenic polycyclic aromatic hydrocarbons in the
      aquatic environment.
AB  - Polycyclic aromatic hydrocarbons (PAHs) represent an ecotoxicologically relevant,
      combustion-related substance group. The bioconcentration and transformation of a
      priority PAH, benzo[a]pyrene (BaP), by brown (Fucus vesiculosus and Chorda
      filum), red (Furcellaria lumbricalis), green (Enteromorpha intestinalis, and
      Cladophora glomerata), and chara (Chara aspera) algae have been studied. A flux
      budget was made of the amounts of BaP that are accumulated and metabolized by
      different algae during an estimated time. The results indicated that of all the
      BaP consumed, 89-99% was found in the biomass of Fucus, an insignificant part was
      in the solution, and the remainder (up to 4%) was not recovered, i.e., was
      considered to have been metabolized. For green and chara algae the proportion of
      transformed PAHs was more essential, 42-49%. The transformation of BaP in marine
      and freshwater algae is species specific and depends on the presence and activity
      of enzymes localized in the plant cells. The most important enzyme systems for
      detoxification of BaP are o-diphenol oxidase, cytochrome P450, and peroxidase.
      The data obtained indicate the important role of marine and freshwater algae in
      the fate of carcinogenic PAHs in the environment.

PMID- 9756695
TI  - Chemical speciation dynamics and toxicity assessment in aquatic systems.
AB  - The key to risk assessment of contaminant effects in the environment (water,
      sediments, soil) is the ability to document cause-and-effect relationships. In
      ecotoxicological research, biotic responses are related to quantified contaminant
      concentrations, which in most cases are still expressed in terms of "total
      elemental concentration" and not in terms of "elemental species." However, it
      becomes evident that the abundance and distribution of pollutants in the
      environment, their bioavailability, and their toxicity to aquatic and terrestrial
      organisms (including humans) can often be better understood in terms of
      "elemental species." The persistence, mobility, chemical reactivity, sorption
      dynamics, and so on of contaminants in soil and water are governed by a range of
      changing physicochemical parameters (pH, temperature, organic matter, suspended
      solids, etc.), which finally dictate the effects at the organism level. Examples
      are given to demonstrate that knowledge of the nature and concentration of
      elemental species of pollutants is crucial in assessing the impact of
      contaminants on aquatic ecosystems. The experimental approach to evaluate
      chemical speciation dynamics in relation to toxic effects is illustrated in a
      case study on the acute toxicity of aluminum in mixing zones at the confluence of
      rivers with different pH values. This study under nonequilibrium ecosystem
      conditions has provided new insights into the mechanism of toxicity of aluminum
      to freshwater organisms. In conclusion, an integrative approach by environmental
      chemists and ecotoxicologists is recommended to evaluate environmental pollution.
      Studies on the assessment of the impact of changing physicochemical parameters on
      the transformation kinetics and chemical speciation of pollutants, which finally
      determine toxicity and bioconcentration in organisms, deserve more attention in
      environmental toxicology.

PMID- 9756696
TI  - Metallothioneins in Arctic bivalves.
AB  - In the framework of an International Association for the Promotion of Cooperation
      with Scientists from the Independent States of the Former Soviet Union (INTAS)
      Project on biodiversity and adaptation strategies of Arctic coastal marine
      benthos, research was focused on the role of metallothioneins as a possible
      indicator of the effect on animals and availability of trace metals in the
      Arctic. Metallothioneins are low-molecular-weight, cysteine-rich proteins known
      to be induced by high environmental levels of trace metals. Specimens of Macoma
      balthica and Mytilus edulis were collected along several Arctic estuaries in the
      White and Pechora seas; whole tissues for M. balthica and the digestive gland and
      gills for M. edulis were dissected, frozen in liquid nitrogen, and lyophilized
      onboard. Metallothionein concentrations were determined by a polarographic assay.
      From the same stations organisms and sediments were also collected for metal
      analysis. The results revealed significant differences in metallothionein
      concentrations among the stations for M. balthica. Similar, although less marked,
      differences were also obtained in the organs of M. edulis. Data on
      metallothionein were compared with trace metal concentrations in both the
      organisms and sediments. Also, the relationship with abiotic factors (salinity)
      and biological variables (size of sampled organisms) was determined. In
      particular, biological variables seemed to influence metallothionein
      concentration in the organisms and their effect should be carefully considered
      for a correct assessment of differences between stations.

PMID- 9756697
TI  - Use of DNA fingerprinting to detect genotoxic effects.
AB  - The effects of environmental pollutants on organisms may be monitored in a number
      of ways and at different levels. In the case of genotoxic chemicals, the effects
      on the DNA may be monitored using a number of biomarker assays capable of
      detecting phenotypic changes as a result of mutation, gross chromosomal
      abnormalities, unscheduled DNA synthesis, DNA adducts (e.g., by 32P postlabeling
      or by ELISA) and DNA strand breaks (e.g., by the alkaline unwinding assay or the
      comet assay); the sensitivity and specificity of these assays are variable.
      Recent developments in molecular biology such as DNA fingerprinting and gene
      amplification by the polymerase chain reaction (PCR) offer new possibilities for
      detecting DNA damage. In this laboratory, whether an alternative biomarker assay
      (using DNA fingerprinting by arbitrarily primed PCR) can reveal differences in
      the DNA fingerprints of individuals from control and polluted areas was
      investigated. The results indicate that DNA fingerprinting by arbitrarily primed
      PCR offers a useful alternative biomarker assay for detection of the genotoxic
      effects of environmental pollutants.

PMID- 9756698
TI  - Biochemical markers for differentiation of exposures to nonplanar polychlorinated
      biphenyls, organochlorine pesticides, or 2,3,7, 8-tetrachlorodibenzo-p-dioxin in
      trout liver.
AB  - The effects of a single intraperitoneal dose of the prototypical contaminant
      nonplanar 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153, 50 mg/kg), p,p'-DDE (50
      mg/kg), or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 200 ng/kg) on the
      activities of hepatic detoxification enzymes were examined in the liver of
      immature rainbow trout (Oncorhynchus mykiss). Different modulations of the tested
      xenobiotics on microsomal cytochrome P450-dependent testosterone hydroxylase
      activities were found: PCB 153 specifically induced 16beta-hydroxylase activity,
      whereas p,p'-DDE decreased cytochrome P4503A-dependent 6beta-hydroxylation as
      well as 16alpha- and 2alpha-hydroxylation. TCDD did not modulate testosterone
      hydroxylase activities, but a strong induction of cytochrome P4501A activity was
      observed after TCDD administration; hence, cytochrome P4501A is not involved in
      the hydroxylation of testosterone. Trout hepatic microsomal glutathione S
      transferase (GST) activity, enhanced by all the xenobiotics tested, was found to
      be a sensitive nonspecific biochemical marker of oxidative stress; cytosolic
      glutathione reductase was a less sensitive indicator of oxidative stress and was
      induced significantly only by treatment with p,p'-DDE. Cytosolic GST activity
      toward ethacrynic acid (GST-ETHA) was induced by PCB 153 or p,p'-DDE, but not by
      TCDD. Modulations of hepatic microsomal testosterone hydroxylase activities and
      induction of GST-ETHA appeared to be suitable biochemical markers of acute
      exposure to nonplanar PCBs and organochlorines that do not induce cytochrome
      P4501A enzymes in rainbow trout, whereas microsomal GST and cytosolic glutathione
      reductase may become early biochemical indicators of oxidative stress.

PMID- 9756699
TI  - Buffer zones for reducing pesticide drift to ditches and risks to aquatic
      organisms.
AB  - Pesticide drift from field sprayers fitted with different types of spray nozzles
      was investigated under various wind speed conditions. Droplet drift was measured
      adjacent to the sprayed field, on the ditch bank, and in the ditch. Measurements
      were carried out in the normal sprayed situation and with an unsprayed buffer
      zone 3 or 6 m wide. The results indicate that there are major differences between
      spray nozzles. Drift deposition increases with wind speed. In the sprayed
      situation and with a wind speed of 0.5 m/s, there was a maximum of 6.0% drift
      deposition halfway down the ditch bank and no drift deposition in the ditch. At 3
      m/s wind speed these figures are 25.1 and 2.2%, respectively. At 5 m/s wind
      speed, 7.2% drift deposition was measured in the ditch. Risk assessment (cf.
      SLOOTBOX model) carried out with 17 pesticides used in the study area indicated
      that at this wind speed, 8 of the 17 pesticides investigated posed a risk to
      aquatic organisms. Creation of a 3-m buffer zone decreases drift deposition in
      the ditch by a minimum of 95%. Adjacent to the buffer zone only 4 of the 17
      pesticides investigated posed a (minor) risk to aquatic organisms. With a 6-m
      buffer zone no drift deposition in the ditch could be measured (wind speed
      maximum, 4.5 m/s). Creating unsprayed crop edges offers good possibilities for
      the protection of aquatic ecosystems. Socioeconomic research among farmers
      indicates that buffer zones, such as unsprayed cereal edges and unsprayed grass
      strips, could well be adopted in agricultural practice.

PMID- 9756700
TI  - Some considerations on the impact on ecological chemical principles in practice
      with emphasis on gold mining and cyanide.

PMID- 9756701
TI  - Accumulation of cadmium in and its effect on bank vole tissues after chronic
      exposure.
AB  - Cadmium is one of many metals that are not physiologically or biochemically
      essential to organisms. This element is extremely dangerous as it is easily
      absorbed and remains in tissues for a long time. Long exposure to high doses of
      cadmium may cause biochemical and functional changes in some critical organs. In
      this study, wheat grains contaminated with cadmium chloride were used to test the
      influence of cadmium on male bank voles (Clethrionomys glareolus). Doses used in
      the experiment were environmentally realistic: 0.25 microg g-1 (control), 15
      microg g-1, and 40 microg g-1 cadmium (dry weight). The animals were given
      cadmium-contaminated food and clean water ad libitum for 3 and 6 months. After
      these exposures, the animals were killed and the kidneys, liver, and testes from
      each vole were collected for analyses. The concentrations of Cd, Cu, Zn, and Fe
      in the tissues were determined with an atomic absorption spectrophotometer. The
      formalin-fixed testes, kidneys, and part of the liver were embedded in paraffin
      and then stained with hematoxylin and eosin. Cadmium accumulation in the tissues
      was directly proportional to dose. The highest cadmium concentrations were found
      in the kidneys of animals fed the highest dose of cadmium. Histological
      examination of the tissues revealed some pathological changes in the structure of
      kidneys, liver, and testes.

PMID- 9756702
TI  - Short- and long-term effects of the pyrethroid insecticide fenvalerate on an
      invertebrate pond community.
AB  - Direct and secondary effects of fenvalerate on the structure of pond ecosystems
      were studied in six freshwater mesocosms simulating natural fish-free eutrophic
      ponds. Exposed mesocosms were compared with nonexposed ones and the effects of
      the added compound on the macroinvertebrate community were followed during three
      vegetation seasons (years) in two mesocosms. Exposure to fenvalerate at 1.3 and
      0.54 microg liter-1 resulted in structural changes in the macroinvertebrate
      community. The insecticide was directly lethal to insects and other arthropods,
      but indirect community changes were also observed. For example, after exposure
      there was a remarkable (> 10-fold) increase in oligochaetes (Stylaria lacustris),
      probably caused by reduced predation and interspecific competition for food. When
      predators (insects) recolonized the system, the oligochaetes decreased in
      abundance and were replaced by ostracods (Herpetocypris reptans), which use
      similar food resources but are less susceptible to predation. The marked increase
      in these two taxa is probably explained by the mass death of arthropods,
      resulting in increased food availability. More than 2 years after treatment, the
      most exposed system was still different compared with nonexposed ones, suggesting
      that nonpersistent pesticides may produce detrimental effects resulting in long
      term changes at the ecosystem level of organization.

PMID- 9756703
TI  - Evaluation of heavy metal sediment toxicity in littoral ecosystems using
      juveniles of the fish Sparus aurata.
AB  - The toxicity of sediments from two littoral ecosystems of the Gulf of Cadiz was
      tested using juveniles of the fish Sparus aurata (seabream). Concentrations of
      total carbon and nitrogen, organic carbon, 14 heavy metals (Fe, Mn, Cu, Zn, Pb,
      Cd, Ag, Hg, As, Sn, V, Ni, Co, Cr), and the surfactant linear alkyl
      benzenesulfonate (LAS) in the sediments were measured. Chemical analysis was
      performed in the stations to determine the degree and nature of contamination.
      Four different endpoints were selected in the toxicity test: survival,
      superficial alteration, hematocrit analysis, and histological damage. After 14
      days, survival, superficial alteration, and hematocrit analysis did not reveal
      effects of the different sediments tested. The histological and cellular damage
      revealed a more sensitive response to measured chemicals in sediments and they
      were found to be a powerful tool to evaluate sediment toxicity effects.
      Semiquantitative evaluation of the histological damage demonstrated correlation
      with sediment concentrations of some of the heavy metals (Cr, Cd, Pb, Ag, Cu) and
      the surfactant (LAS). Data derived from chemical concentrations and toxicity
      tests were assembled by multivariate statistical techniques (principal components
      analysis) to identify the ranges of chemical concentrations associated with an
      adverse effect. The results obtained, as suggested by site-specific sediment
      quality values, were the following: Cr>/=90.2; Cd>/=1.24; Pb>/=52.5; Ag>/=0.68;
      Cu>/=71.2; LAS>/=8.7 mg kg-1 of dry sediment. These results are mainly in
      concordance with studies performed in other areas of the world and therefore
      support wide application of the method.

PMID- 9756704
TI  - Liver energy metabolism of Anguilla anguilla after exposure to fenitrothion.
AB  - This paper deals with the effect of fenitrothion (0.04 mg/liter) on the energy
      metabolism of the European eel, Anguilla anguilla, and its recovery from
      intoxication. Various parameters such as glycogen, lactate, proteins, total
      lipids, and glucose in eel liver and blood were analyzed after 2, 8, 12, 24, 32,
      48, 56, 72, and 96 h of fenitrothion exposure. Subsequently, the fish were
      allowed recovery periods of 8, 12, 24, 48, 72, 96, 144, and 192 h in clean water,
      and the same parameters were evaluated. Liver glycogen and lipid contents
      decreased significantly during the exposure, while blood glucose levels increased
      markedly. Liver and blood lactate values increased during pesticide exposure,
      while proteins were decreased in comparison to unexposed controls. Most of the
      metabolic disorders did not persist after less than a week of recovery in clean
      water. The observed effects of fenitrothion on fish metabolism are discussed in
      relation to a stress syndrome, and probable reasons for alterations are also
      discussed.

PMID- 9756705
TI  - Toxicity of ozone to fish larvae and Daphnia magna.
AB  - Ozone can be used as an alternative to chlorination to control biofouling in
      cooling water systems. The possible negative environmental impact of a discharge
      of ozone-containing cooling water was investigated. The acute toxicity of
      dissolved ozone was determined for fish larvae of three species [Cyprinus carpio
      (at 27 degrees C), Leuciscus idus (at 27 degrees C) and Clarias gariepinus (at 32
      degrees C)] and to Daphnia magna (at 21 and 27 degrees C). The results indicate
      that ozone is very harmful to aquatic life. Daphnids are more sensitive to ozone
      than fish larvae. The mean 48-h LC50 value for the larvae amounts to about 35
      microg/liter, while the 48-h NOEC for D. magna was 11 microg/liter (at 21 degrees
      C). It was concluded that, to protect aquatic life, discharged cooling water
      should not contain any dissolved ozone. This can be achieved in practice by
      mixing the treated cooling water with a source of organic substances before
      discharge, as free ozone will react immediately with organic matter and thus
      disappear.

PMID- 9756706
TI  - Study of alterations produced by cadmium and cadmium/lead administration during
      gestational and early lactation periods in the reproductive organs of the rat.
AB  - Administration of cadmium (10 mg/liter) and cadmium+lead (300 mg/liter) via
      drinking water to Wistar rats during gestation and early lactation until delivery
      and (5 days after parturition) damaged pup reproductive systems. The effects are
      additive in the decreased gonad weight and additive or even synergistic in the
      reduced DNA gonadal content. The effects on protein reduction are similar for
      both cations. In the testes, the effects of cadmium are more important in the
      reduction of seminiferous tubule diameter, whereas the effects of lead are more
      overt in the reduction of the number of prospermatogonia.

PMID- 9756707
TI  - Modulation of drug-metabolizing systems by bacterial endotoxin in carp liver and
      immune organs.
AB  - This report describes a study of the effects of bacterial endotoxin
      [lipopolysaccharide (LPS)] on cytochrome P450 levels and ethoxyresorufin O
      deethylase (EROD) and glutathione S-transferase (GST) activities in liver and two
      main immune organs of carp: spleen and head kidney. Also studied was the paucity
      of the carp drug-metabolizing system in an environment subject to pollution by a
      polycyclic aromatic hydrocarbon, 3-methylcholanthrene (3MC), when fish respond to
      an immune activation by lipopolysaccharide (LPS). In the presence of bacterial
      endotoxin the basal cytochrome P450 levels were decreased in liver and spleen.
      EROD activity was increased in liver and basal GST activity was increased in
      spleen. When fish were treated concomitantly with 3MC and LPS, a suppression of
      cytochrome P450 induction in liver and head kidney was observed. EROD activity
      induced by 3MC was not modified by administration of LPS. GST activity was
      suppressed by treatment with LPS and inducing agent in liver and head kidney. In
      the present study it was found that endotoxin can have profound and differential
      effects on fish basal biotransformation of drugs in the liver and immune organs.
      Also, the induction of biotransformation enzymes by 3MC was modified when fish
      responded to an immune stimulation.

PMID- 9756708
TI  - Osmotic effects as a factor modifying insecticide toxicity on Aedes and Artemia.
AB  - Euryhaline species are more tolerant of various insecticides under isosmotic
      conditions. Two euryhaline species, Aedes taeniorhynchus (Wiedemann) and Artemia
      sp., were exposed to four insecticides (aldicarb, dimethoate, imidacloprid,
      tebufenozide), under isosmotic and hyperosmotic conditions. Mortality under these
      two osmotic conditions was observed and compared to evaluate salinity as a
      contributing factor to insecticide toxicity. Artemia was more tolerant of all
      chemicals tested than A. taeniorhynchus under isosmotic conditions based on the
      percentage mortality observed. Mortality of Artemia under isosmotic conditions
      was dependent on the length of exposure; A. taeniorhynchus did not exhibit time
      dependence. Less mortality was observed in populations of both test species under
      isosmotic conditions compared with hyperosmotic conditions. However, the
      variation in mortality due to exposure to test chemicals was of greater magnitude
      in A. taeniorhynchus than Artemia. This result indicates that higher salinity is
      a greater stress on A. taeniorhynchus than Artemia when exposed to the test
      insecticides at the concentration ranges tested in this study.

PMID- 9756709
TI  - The freshwater river crab, Potamonautes warreni, as a bioaccumulative indicator
      of iron and manganese pollution in two aquatic systems.
AB  - The aim of this study was to determine the potential use of the freshwater river
      crab, Potamonautes warreni, as a bioaccumulative indicator of iron and manganese
      pollution in aquatic ecosystems. Water and sediment analysis of the two study
      sites (Germiston Lake and Potchefstroom Dam) revealed that while levels of
      manganese were higher in Germiston Lake, iron concentrations were higher in
      Potchefstroom Dam. Metal analysis of P. warreni revealed that while the crabs
      from Potchefstroom Dam contained slightly higher iron levels than those from
      Germiston Lake, manganese concentrations in P. warreni from the latter site were
      significantly higher than those in the crabs from the former site. Iron and
      manganese levels in these organisms were influenced by the size, mass, and sex of
      the crabs on occasion, but these relationships were not always consistent at both
      of the sites. The results of this study clearly indicate that the ultimate levels
      of iron and manganese attained in P. warreni do vary depending on the site from
      which animals are collected. From this, it is suggested that these crustaceans be
      incorporated into biomonitoring protocols, particularly in areas that are
      subjected to elevated metal levels in the environment

PMID- 9756710
TI  - Fungal avirulence genes: structure and possible functions.
AB  - Avirulence (Avr) genes exist in many fungi that share a gene-for-gene
      relationship with their host plant. They represent unique genetic determinants
      that prevent fungi from causing disease on plants that possess matching
      resistance (R) genes. Interaction between elicitors (primary or secondary
      products of Avr genes) and host receptors in resistant plants causes induction of
      various defense responses often involving a hypersensitive response. Avr genes
      have been successfully isolated by reverse genetics and positional cloning. Five
      cultivar-specific Avr genes (Avr4, Avr9, and Ecp2 from Cladosporium fulvum; nip1
      from Rhynchosporium secalis; and Avr2-YAMO from Magnaporthe grisea) and three
      species-specific Avr genes (PWL1 and PWL2 from M. grisea and inf1 from
      Phytophthora infestans) have been cloned. Isolation of additional Avr genes from
      these fungi, but also from other fungi such as Uromyces vignae, Melampsora lini,
      Phytophthora sojae, and Leptosphaeria maculans, is in progress. Molecular
      analyses of nonfunctional Avr gene alleles show that these originate from
      deletions or mutations in the open reading frame or the promoter sequence of an
      Avr gene. Although intrinsic biological functions of most Avr gene products are
      still unknown, recent studies have shown that two Avr genes, nip1 and Ecp2,
      encode products that are important pathogenicity factors. All fungal Avr genes
      cloned so far have been demonstrated or predicted to encode extracellular
      proteins. Current studies focus on unraveling the mechanisms of perception of
      avirulence factors by plant receptors. The exploitation of Avr genes and the
      matching R genes in engineered resistance is also discussed.

PMID- 9756711
TI  - Phylogeny of the genus trichoderma based on sequence analysis of the internal
      transcribed spacer region 1 of the rDNA cluster 
AB  - Sequences of the internal transcribed spacer region 1 (ITS1) of the ribosomal DNA
      were used to determine the phylogenetic relationships of species of Trichoderma
      sect. Pachybasium. To this end, 85 strains-including all the available ex-type
      strains-were analyzed. Parsimony analysis demonstrated that the section is
      nonmonophyletic, distributing the 85 strains among three main groups that were
      supported by bootstrap values. Group A comprises two clades (A1 and A2), with A1
      including T. polysporum, T. piluliferum, and T. minutisporum, while A2 included
      T. hamatum, T. pubescens, and T. strigosum in addition to species previously
      included in sect. Trichoderma (i.e., T. viride, T. atroviride, and T. koningii).
      The ex-type strain of T. fasciculatum formed a separate branch basal to clade A.
      Clade B contained the sect. Pachybasium members T. harzianum, T. fertile, T.
      croceum, T. longipile, T. strictipile, T. tomentosum, T. oblongisporum, T.
      flavofuscum, T. spirale, and the anamorphs of Hypocrea semiorbis and H. cf.
      gelatinosa. Sequence differences among clades A1, A2, and B were in the same
      order of magnitude as between each of them and T. longibrachiatum, which was used
      as an outgroup in these analyses. Sequence differences within clades A1, A2, and
      B were considerably smaller: in some cases (i.e., T. virens and T. flavofuscum;
      T. strictipile and H. cf. gelatinosa), the ITS1-sequences were identical,
      suggesting conspecifity. In other cases (e.g., T. crassum and T. longipile; T.
      harzianum, T. inhamatum, T. croceum, T. fertile, and H. semiorbis; T. hamatum and
      T. pubescens; and T. viride, T. atroviride, and T. koningii) differences were in
      the range of 1-3 nt only, suggesting a very close phylogenetic relationship. The
      sequence of a previously described aggressive mushroom competitor group of T.
      harzianum strains (Th2) was strikingly different from that of the ex-type strain
      of T. harzianum and closely related species and is likely to be a separate
      species. Copyright 1998 Academic Press.

PMID- 9756712
TI  - Regulation of hsp90 and hsp70 genes during antheridiol-induced hyphal branching
      in the oomycete Achlya ambisexualis.
AB  - When mycelia of Achlya ambisexualis J. Raper strain E87 were undergoing
      antheridial branching, a marked increase was observed in the levels of transcript
      populations encoding the heat shock protein chaperone Hsp90 and transcript
      populations encoding three different Hsp70-family heat shock protein chaperones,
      respectively. Although up to 90% of hyphae in the hormone-treated thalli were
      undergoing antheridial branching, no similar increase in the level of transcripts
      encoding actin was observed. Nuclear run-on assays demonstrated that the observed
      antheridiol-induced increases in the levels of the chaperone RNAs resulted from
      increased transcription. Although not tested for function, the nucleotide
      sequence of the 5' flanking region of each of the two A. ambisexualis hsp90 genes
      revealed a diversity of sequences and motifs similar or identical to the
      sequences of known transcription factor response elements. Among these potential
      response element sequences observed in the A. ambisexualis genes were motifs
      observed also in animal steroid hormone response elements. Surrounding the primer
      extension determined transcription start site of each A. ambisexualis hsp90 gene
      was a 16-nucleotide sequence that matched in 14 out of 16 nucleotides a sequence
      found in the transcription initiation region of many different oomycete genes.

PMID- 9756714
TI  - In vivo addition of telomeric repeats to foreign DNA generates extrachromosomal
      DNAs in the taxol-producing fungus Pestalotiopsis microspora.
AB  - Transformation of the taxol-producing filamentous fungus Pestalotiopsis
      microspora with a plasmid containing the bacterial hygromycin resistance gene
      fused to Aspergillus regulatory sequences resulted in the in vivo formation of
      extrachromosomal DNAs with telomeric repeats in the majority of transformants.
      Repeats of the telomeric sequence 5'-TTAGGG-3' were appended to nontelomeric
      transforming DNA termini. No fungal sequences other than telomeric repeats were
      detected in extrachromosomal DNAs. Transformants contained three to six different
      sizes or conformational forms of extrachromosomal DNAs. The DNAs showed no change
      in size or internal structure during 6 months of growth with selection, but were
      lost after 20 days of growth without selection. Transformation of wild-type P.
      microspora with a PCR-amplified extrachromosomal DNA having terminal telomeric
      repeats produced up to 50-fold more transformants than the original
      transformation vector. The addition of telomeric repeats to foreign DNA is
      unusual among fungi and may have important adaptive or developmental
      implications.

PMID- 9756713
TI  - Relationships of the insect-pathogenic order Entomophthorales (Zygomycota, Fungi)
      based on phylogenetic analyses of nuclear small subunit ribosomal DNA sequences
      (SSU rDNA).
AB  - We sequenced the nuclear small subunit of ribosomal DNA (SSU rDNA) from seven
      species within the insect-pathogenic order Entomophthorales. These sequences were
      aligned with other published SSU rDNA sequences and phylogenies were inferred
      using phenetic and cladistic methods. Based on three different phylogenetic
      methods the Entomophthorales (excluding Basidiobolus ranarum) is monophyletic; B.
      ranarum was more closely related to chytrids from Chytridiales and
      Neocallimasticales than to Entomophthorales, as was proposed by Nagahama et al.
      (Mycologia 87: 203-209, 1995). Nuclear characters (large nuclei containing
      conspicuous condensed chromatin and lack of a prominent nucleolus) were of
      predictive value for the monophyly of the family Entomophthoraceae. Conidial
      characters separate the Entomophthoraceae, which only includes obligate
      pathogens, into at least two lineages: one lineage with uninucleate conidia and
      another with multinucleate conidia. The two species of Conidiobolus studied were
      paraphyletic in our analyses and only distantly related to each other. This
      information may prove to be important in the use of these fungi as biocontrol
      agents.

PMID- 9756715
TI  - A cell-free translation-translocation system reconstituted with subcellular
      fractions from the wall-less variant fz;sg;os-1V of Neurospora crassa.
AB  - A translation-translocation system reconstituted with subcellular fractions from
      the wall-less variant fz;sg;os-1V of Neurospora crassa reproduces in vitro
      translocation and processing of a secretory protein. The translation extract was
      isolated from the wall-less variant by gently lysing cells by a freeze-thaw
      procedure. This method yielded more extract then the method developed previously
      (R. Addison, J. Biol. Chem. 262: 17031, 1987) as well as reducing microsomal
      contamination. The microsomal fraction was isolated from lysed cells using a
      series of discontinuous sucrose gradients. The resultant microsomes were less
      inhibitory to translation of various transcripts and consisted of a more
      homogenous mixture of vesicles then microsomes prepared previously. Polyclonal
      antibodies directed against a polypeptide of approximately 75 kDa from the
      microsomes were used in indirect-immunofluorescence microscopy. The resultant
      fluorescent pattern shows a network of tubulo-reticular structures in a
      juxtanuclear region, which is the pattern expected of the rough endoplasmic
      reticulum.

PMID- 9756716
TI  - Evolution of spore release mechanisms in the saprolegniaceae (Oomycetes):
      evidence from a phylogenetic analysis of internal transcribed spacer sequences 
AB  - Classical studies on spore release within the Saprolegniaceae (Oomycetes) led to
      the proposition that different mechanisms of sporangial emptying represent steps
      in an evolutionary transition series. We have reevaluated this idea in a
      phylogenetic framework using internal transcribed spacer sequences of four
      genera. These data were compared with the response to osmotic stress exhibited by
      each taxon. Saprolegnia emerges as the most basal genus, sister to Achlya,
      Thraustotheca, and Dictyuchus. Achlya and Thraustotheca are most closely related,
      while Dictyuchus appears to have evolved along a separate evolutionary lineage.
      The resulting phylogenetic framework is consistent with the idea that the
      mechanism of sporangial emptying exhibited by Saprolegnia represents the
      plesiomorphic condition from which the other mechanisms were derived
      independently. These alternative mechanisms of spore release may have resulted
      from a small number of mutations that inhibited axonemal development and altered
      the temporal and spatial expression of lytic enzymes that degrade the sporangial
      wall. Copyright 1998 Academic Press.

PMID- 9756717
TI  - Characterization and molecular genetic complementation of mutants affecting
      dimorphism in the fungus ustilago maydis 
AB  - Ustilago maydis, the causal agent of corn smut disease, displays dimorphic growth
      in which it alternates between a unicellular, nonpathogenic yeast-like form and a
      dikaryotic, pathogenic filamentous form. Previously, a constitutively filamentous
      haploid mutant was obtained. Complementation of this mutant led to the isolation
      of the gene encoding adenylate cyclase, uac1. Secondary mutagenesis of a uac1
      disruption strain allowed the isolation of a large number of suppressor mutants,
      termed ubc, for Ustilago bypass of cyclase, lacking the filamentous phenotype.
      Analysis of one of these suppressor mutants previously led to the identification
      of the ubc1 gene, encoding the regulatory subunit of cAMP-dependent protein
      kinase. In this report we describe the isolation of cosmids containing three new
      ubc genes, termed ubc2, ubc3, and ubc4. We also describe the morphology of the
      ubc2, ubc3, and ubc4 mutants in a uac1- background as well as in a background
      with a functional uac1 gene. In addition, we describe several mutant strains not
      complemented with any of the genes currently in hand and that are thus presumed
      to possess mutations in additional ubc genes. Copyright 1998 Academic Press.

PMID- 9756718
TI  - New opportunities for the treatment of severe autoimmune diseases: bone marrow
      transplantation.

PMID- 9756719
TI  - Proposed CD4(+) T-cell criteria for staging human immunodeficiency virus-infected
      Chinese adults.
AB  - The present treatment, prophylaxis, and prognostic staging of human
      immunodeficiency virus (HIV) disease rely heavily on peripheral CD4(+) T
      lymphocyte (CD4) changes. We correlated the clinical course of events and CD4
      changes among consecutive HIV-infected ethnic Chinese adults in Hong Kong. Using
      death as end point, the estimated proportion survival and death incidences were
      used to compare CDC and proposed staging criteria based on stratified baseline
      CD4. A separate set of baseline CD4 per microliter (/microl) (percentage
      lymphocytes) stratification criteria of 1, >220/microl (>12%); 2, 100-220/microl
      (6-12%); and 3, <100/microl, (<6%) is proposed which can be used for staging HIV
      infected Chinese adults. For our study population, our proposed criteria for
      stratifying baseline CD4 gave better discrimination and more predictive power
      than the CDC criteria. We assessed the potential impact of these new proposed
      criteria on anti-retroviral treatment and prophylaxis against opportunistic
      infections in our adult HIV-infected population.

PMID- 9756720
TI  - Circulating Toxoplasma gondii-specific antibody-secreting cells in patients with
      congenital toxoplasmosis.
AB  - Patients with congenital toxoplasmosis occasionally show rises in serum
      antibodies to Toxoplasma gondii (serological rebound), but the underlying cause
      remains unclear. The acute or chronic presence of available antigen often causes
      the appearance, in the peripheral blood, of cells actively secreting specific
      antibody. We have evaluated the capacity of circulating blood cells from 91
      children born to T. gondii-infected mothers to actively synthesize anti-T. gondii
      antibodies according to their serological status. Supernatants from 7-day
      cultures of peripheral blood mononuclear cells were evaluated for antibody by
      cytofluorimetry. Only 1 of 49 subjects with low and stable serum antibody titers
      produced specific antibodies on cultures, while 9 of 22 subjects with recent
      rebound were positive. One of the positive children alone showed clinical signs
      of parasite activity. These observations suggest that rebound may be associated
      with production of available parasite antigens, possibly associated with
      reactivation. Differentiation from other causes, such as polyclonal B cell
      stimulation, would improve our ability to detect clinically significant
      reactivation and to prevent complications.

PMID- 9756721
TI  - The expression and localization of fibroblast growth factor-1 (FGF-1) and FGF
      receptor-1 (FGFR-1) in human breast cancer.
AB  - Fibroblast growth factor-1 (FGF-1) is an inducer of angiogenesis, the growth of
      new blood vessels. The expression and localization of FGF-1 (acidic FGF) and FGF
      receptor (FGFR)-1 in mammary tissues from patients with breast cancer was
      investigated using Western blot analysis and immunohistochemistry. The affinity
      purified FGF-1 antibody which did not have cross-reactivity to FGF-2 (basic FGF)
      was used in this study. Western blot analysis demonstrated the presence of FGF-1
      protein in all of the samples from breast cancer, but not benign tumors such as
      mastopathy and fibroadenoma. To assess the localization of FGF-1 in cancer
      tissues, immunostaining with specific antibody was performed. All samples from
      breast cancer displayed significantly intense staining with FGF-1 antibody. The
      extent and intensity of immunoreactive FGF-1 polypeptides in cancer cells was
      statistically much greater than those of cells from fibroadenoma or mastopathy.
      Control immunostaining with normal rabbit serum or anti-FGF-1 antibody adsorbed
      with the recombinant FGF-1 polypeptide was completely negative. In contrast to
      FGF-1, Western blot analysis demonstrated the presence of FGFR-1 protein in all
      of the samples from breast cancer and benign tumors. By immunohistochemical
      analysis, the enhanced expression of FGFR-1 was observed in breast cancer cells.
      Benign tumor cells or interstitial cells displayed a faint expression of FGFR-1.
      These results demonstrated that breast cancer cells not only generated FGF-1, but
      also expressed FGFR-1, and FGF-1 might play a role in the proliferation of breast
      cancer cells not only by paracrine but also by autocrine mechanism.

PMID- 9756722
TI  - Determination of primary amino acid sequence and unique three-dimensional
      structure of WGH1, a monoclonal human IgM antibody with anti-PR3 specificity.
AB  - Transformed B cells making monoclonal IgM-lambda anti-PR3 antibody WGH1 from a
      patient with Wegener's granulomatosis were used to prepare mRNA and synthesize
      cDNA. PCR primers for human micro and lambda chains were then employed to amplify
      heavy- and light-chain V-regions followed by cloning into pCR2-1 vector and
      sequencing. Molecular modeling of VH regions employed knowledge-based homology
      modeling to obtain minimum energy conformation. The VH sequence was subgroup III
      with marked overall homology to VH1.9III. The VHCDR3 region of WGH1 was unique,
      consisting of 21 amino acid residues which included seven tyrosines as well as
      three negatively charged aspartic acid residues. The VL region was subgroup II
      with a negatively charged glutamic acid at position 100 in CDR3. Molecular
      modeling of VH revealed a major conformational difference in the shape of CDR3
      compared with other antibodies for which three-dimensional structures have been
      determined. Monoclonal antibody WGH1 reacting with PR3 (a highly positively
      charged molecule) shows a unique reactive cassette within VHCDR3 with a number of
      negatively charged aspartic acid residues. WGH1 VHCDR3 contains a loop which
      shows a major projection not usually recorded in other previously studied
      antibody molecules.

PMID- 9756724
TI  - Adhesion molecules in tissue injury: kinetics of expression and shedding and
      association with cytokine release in humans.
AB  - Adhesion molecules are responsible for leukocyte recruitment in injured tissues.
      Here, the kinetics of expression and shedding of endothelial (sE-selectin-1, sP
      selectin, and sICAM-1) and neutrophil (CD11b, CD62L, and CD54) adhesion molecules
      was investigated by serial determinations of serum concentrations in 20 patients
      with elective hip arthroplasty as an exemplary condition of acute inflammation in
      humans. Changes were related to secretion of proinflammatory cytokines (IL-1beta,
      IL-6, IL-8, and TNF-alpha) as their possible inducing signals. sE-selectin-1
      responded to injury with a significant increase in concentrations already after
      20 min, followed by sP-selectin and sICAM-1, which increased at Hour 10 and Day
      1. Expression of CD11b and CD62L acutely responded to injury (within 1 h) by a
      parallel increase and decrease, respectively, and normalized by Day 1. Increases
      in concentrations of IL-1beta and TNF-alpha preceded the increase in adhesion
      molecules and significantly correlated with the response of sE-selectin-1 and
      sICAM-1. In conclusion, the close associations between release of IL-1beta and
      TNF-alpha and sE-selectin and sICAM-1 shown in this kinetic study indicates a key
      role of these cytokines in upregulation of endothelial rather than neutrophil
      adhesion molecules in vivo.

PMID- 9756723
TI  - RANTES expression and contribution to monocyte chemotaxis in arthritis.
AB  - Rheumatoid arthritis (RA) is characterized by recruitment of leukocytes from the
      vasculature into inflamed synovial tissue (ST) and synovial fluid (SF), which
      depends, in part, upon the continued maintenance of chemotactic stimuli. RANTES
      is a potent chemoattractant for leukocytes including monocytes and CD45RO+ memory
      T lymphocytes. The aim of this study was to determine the production, the source,
      and the function of antigenic RANTES in arthritis. We detected antigenic RANTES
      in SFs from RA and OA patients (100 +/- 22.7 and 72 +/- 30.7 pg/ml,
      respectively). CM from RA ST fibroblasts stimulated with interleukin-1beta or
      tumor necrosis factor-alpha contained significantly more antigenic RANTES than
      unstimulated CM (452 +/- 181.6 and 581 +/- 200.2 pg/ml, respectively, versus 12
      +/- 4.4 pg/ml, P < 0.05). PHA-stimulated RA SF mononuclear cells secreted 5- to
      15-fold more antigenic RANTES than did nonstimulated mononuclear cells, while LPS
      induced secretion up to 4-fold. We immunolocalized antigenic RANTES to sublining
      macrophages (28 +/- 3.7 and 8 +/- 2.0% immunopositive cells), perivascular
      macrophages (56 +/- 6.9 and 19 +/- 3.4%), and synovial lining cells (37 +/- 5.8
      and 60 +/- 10.4%) in RA and OA tissue, respectively. Anti-RANTES neutralized 20.2
      +/- 1.3% of the RA SF chemotactic activity for normal peripheral blood monocytes
      (P < 0.05). These results demonstrate antigenic RANTES in RA and OA ST and SF and
      identify RANTES as a chemoattractant for monocytes in the RA joint.

PMID- 9756725
TI  - Age-related persistent clonal expansions of CD28(-) cells: phenotypic and
      molecular TCR analysis reveals both CD4(+) and CD4(+)CD8(+) cells with identical
      CDR3 sequences.
AB  - In a small group of subjects we had identified persistent expansions (range 6
      72%) of CD4(+)CD8(+) double-positive (DP) peripheral blood (PB) cells which
      express the CD8 alpha/alpha homodimer. Here, DP cells present in a larger cohort
      were further investigated and found by FACS analysis to express a single or a
      dominant TCRBV family. In these subjects, with a mean age of about 64 years,
      expansions of CD4(+) cells with the same TCRBV family specificity as in the
      respective DP cells also were consistently detected. TCR heterogeneity of the
      dominant TCRBV family was specifically evaluated: The amplified CDR3 region was
      cloned and found to consist of one single or two largely dominant sequence
      patterns. Furthermore, cloning of the CDR3 region from FACS-sorted DP, CD4(+), or
      CD8(+) cells indicates that both DP and CD4(+), but not CD8(+) cells, isolated
      from the same individual possess a striking identity of the CDR3 regions. As
      indicated by FACS analysis, the clonally expanded cells occur in the CD4(+)CD28(
      ) cells. Taken together, these results suggest that expanded CD4(+)CD28(-) cells
      might also acquire CD8 alpha/alpha expression and become DP and imply that CD4
      clonality is a more frequent phenomenon than previously suspected. In conclusion,
      the persistent expansions described in this report represent a novel group of age
      related benign clonal expansions of still undefined significance of a rare CD28(
      ) T cell subset.

PMID- 9756726
TI  - Analysis of autoantibodies against RNA polymerases using immunoaffinity-purifed
      RNA polymerase I, II, and III antigen in an enzyme-linked immunosorbent assay.
AB  - Autoantibodies against RNA polymerases (RNAP) have been reported to occur in
      patients with a wide variety of connective tissue diseases (CTD), including
      systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and mixed
      connective tissue disease (MCTD). The frequency of anti-RNAP antibodies has been
      reported to vary widely between different CTD diseases in studies examining
      different patient populations. Furthermore, these studies have been limited by
      the fact that methods have not previously been available for detecting antibodies
      against RNAP which are both rapid and quantitative. We have developed an enzyme
      linked immunosorbent assay (ELISA) for rapidly quantitating antibodies against
      RNAP I, II, and III. We have utilized both the ELISA and the immunoprecipitation
      of 35S-labeled HeLa cells to analyze sera from a large cohort of well
      characterized Caucasian CTD patients for the presence of anti-RNAP antibodies. We
      found excellent concordance for the presence of anti-RNAP antibodies using
      immunoprecipitation and ELISA. Anti-RNAP antibodies occurred predominantly among
      female patients with the diffuse form of SSc and were detected in 8/36 (22%) of
      Caucasian patients with diffuse SSc and 1/53 (2%) with limited SSc. Anti-RNAP
      antibodies occurred in 1/42 (2%) of patients with SLE. Anti-RNAP antibodies did
      not occur in MCTD (0/49). Antibodies against RNAP were rare among antinucleolar
      reactive sera, occurring in only 3/200 (1.5%). The RNAP ELISA provides a
      validated method which can be rapidly utilized in a clinical diagnostic
      laboratory setting to identify SSc patients who are at risk for developing
      diffuse SSc with multiorgan involvement and hypertensive renal crisis.

PMID- 9756727
TI  - CD44 variant isoform expression in a variety of skin-associated autoimmune
      diseases.
AB  - CD44 variant isoforms are frequently expressed on tissue-infiltrating
      lymphocytes. By the high incidence of autoimmune reactions of the skin and aiming
      at new strategies of therapeutic intervention, we became interested in evaluating
      the CD44 isoform expression profile in autoimmune reactions of the skin.
      Expression of CD44s, CD44v3, v5, v6, v7, v7-v8, and v10 was evaluated in 55
      biopsies of lupus erythematosus, bullous pemphigoid, vasculitis, morphea, and
      pemphigus vulgaris. Biopsies did not contain CD44v5-, CD44v6-, CD44v7-, or CD44v7
      v8-positive leukocytes. Staining with anti-CD44v10 was seen in vasculitis and
      occasionally in lupus erythematosus, morphea, and bullous pemphigoid. All
      biopsies contained CD44v3(+) leukocytes, the percentage of CD44v3(+) leukocytes
      being increased in autoimmune infiltrates with the exception of pemphigus
      vulgaris. CD44v3 was expressed by CD4(+) cells as well as by part of CD8(+)
      cells, Langerhans cells, and monocytes. Vascular endothelium also contained
      CD44v3(+) cells. Only monocytes expressed CD44v10. We assume that CD44v3 and
      CD44v10 may be targeting leukocytes toward the skin or allow for their retention
      and expansion via binding of cytokines and chemokines harbored by activated, skin
      associated endothelium or provided by cells surrounding the infiltrate. The
      absence of CD44v6, frequently associated with lymphocyte activation, appears to
      be a peculiarity of skin-infiltrating leukocytes.

PMID- 9756728
TI  - Soluble proteins isolated from Borrelia burgdorferi by extraction with Triton X
      114 confer resistance to experimental infection.
AB  - Fractionation of Borrelia burgdorferi was made by extraction of infectious
      spirochetes using the detergent Triton X-114. Gel electrophoresis analysis of
      hydrophilic and hydrophobic proteins demonstrated that detergent extraction
      resulted in two populations of proteins with nonoverlapping electrophoretic
      profiles. Immunoblot analysis with monoclonal antibodies reactive with two
      abundant membrane proteins demonstrated that hydrophilic proteins were
      uncontaminated with hydrophobic proteins. In addition, assay of thymidine
      incorporation into and secretion of tumor necrosis factor-alpha from splenocytes
      cocultured in vitro with either detergent or aqueous phase proteins showed that
      lymphocyte mitogenic and macrophage activation activities of B. burgdorferi were
      completely absent from the hydrophilic phase proteins. The Triton X-114 aqueous
      and detergent phase proteins were used to immunize BALB/c and separately
      microMT/microMT (B cell knockout) mice that were subsequently challenged with
      infectious B. burgdorferi. The hydrophilic phase proteins were able to induce
      protective resistance to infection in either strain of mice demonstrating that
      potential candidate vaccine antigens are contained in the biochemical class of
      antigens which is devoid of both lymphocyte mitogen activity and major outer
      surface proteins. Furthermore, the ability to vaccinate B cell knockout mice
      suggests that the humoral antispirochete immune response is not the exclusive
      basis for protective immunity.

PMID- 9756729
TI  - Serological association of measles virus and human herpesvirus-6 with brain
      autoantibodies in autism.
AB  - Considering an autoimmunity and autism connection, brain autoantibodies to myelin
      basic protein (anti-MBP) and neuron-axon filament protein (anti-NAFP) have been
      found in autistic children. In this current study, we examined associations
      between virus serology and autoantibody by simultaneous analysis of measles virus
      antibody (measles-IgG), human herpesvirus-6 antibody (HHV-6-IgG), anti-MBP, and
      anti-NAFP. We found that measles-IgG and HHV-6-IgG titers were moderately higher
      in autistic children but they did not significantly differ from normal controls.
      Moreover, we found that a vast majority of virus serology-positive autistic sera
      was also positive for brain autoantibody: (i) 90% of measles-IgG-positive
      autistic sera was also positive for anti-MBP; (ii) 73% of measles-IgG-positive
      autistic sera was also positive for anti-NAFP; (iii) 84% of HHV-6-IgG-positive
      autistic sera was also positive for anti-MBP; and (iv) 72% of HHV-6-IgG-positive
      autistic sera was also positive for anti-NAFP. This study is the first to report
      an association between virus serology and brain autoantibody in autism; it
      supports the hypothesis that a virus-induced autoimmune response may play a
      causal role in autism.

PMID- 9756730
TI  - Effects of endotoxin on lung pericytes in vitro.
AB  - Lipopolysaccharide released during bacterial sepsis causes acute lung injury and
      ARDS. Pulmonary microvascular injury is a feature of ARDS, and vascular
      remodeling develops, leading to pulmonary hypertension. Pericytes in the lung
      circulation proliferate and contribute to the remodeling seen in experimental
      sepsis. It is unknown whether endotoxin can directly stimulate pericyte growth or
      induce contraction. We show that lipopolysaccharide from Escherichia coli,
      Pseudomonas aeruginosa, and Klebsiella pneumoniae increases rat lung pericyte
      proliferation in vitro by up to 72% on day 7 of exposure (P < 0.001), with E.
      coli being most potent. Lipid A is the active portion of the lipopolysaccharide,
      with equal activity at one-tenth the dose of lipopolysaccharide. Endotoxin's
      mitogenic effect requires the presence of serum, consistent with the requirement
      for a soluble CD14 receptor in the serum. Using FACS analysis, the pericytes lack
      surface CD14 receptors. Lipopolysaccharide exposure rapidly increases
      intracellular calcium and induces contraction of pericytes plated onto silicone
      membranes. Thus, endotoxin is a direct mitogen for lung pericytes in vitro and
      also induces pericyte contraction. Endotoxin, present in lung tissue early during
      sepsis, might directly contribute to the vascular remodeling in sepsis-induced
      lung injury.

PMID- 9756731
TI  - Capillary density and leukocyte adhesion in hamsters with hereditary
      cardiomyopathy.
AB  - The aim of this study was to characterize microvascular networks in cheek pouch
      of cardiomyopathic Syrian hamster (CM) (Bio 14.6), which is an interesting model
      of idiopathic cardiomyopathy and congestive heart failure. Microcirculation was
      visualized by fluorescence microscopy. Diameter and length of arterioles,
      classified according to centrifugal ordering scheme, were measured. A
      computational method was arranged to determine the density of arterioles and
      capillaries (total vessel length per unit area, cm-1), fractal dimension of
      capillaries, and the associated Voronoi tesselation. Furthermore, leukocyte
      adhesion to venules and arteriolar reactivity to drugs were studied. Increase in
      the number of terminal arterioles and capillary rarefication characterized CM
      microvasculature compared with that of age-matched controls (58 +/- 7 versus 25
      +/- 5 cm-1, and 128 +/- 15 versus 240 +/- 10 cm-1, respectively). Fractal
      dimension of capillaries was reduced in CM compared with controls (1. 40 +/- 0.10
      versus 1.85 +/- 0.09) and associated with increased avascular spaces, as shown by
      Voronoi tesselation results. Leukocyte adhesion to venules increased
      significantly in CM. In CM responsiveness of arterioles to nitric oxide
      inhibition and propranolol was slighter but more marked to norepinephrine and
      angiotensin II compared with that of control hamsters. In conclusion, the
      different geometry, increased leukocyte adhesion, and altered arterial
      responsiveness may contribute to flow disturbances in the microcirculation of CM
      hamsters.

PMID- 9756732
TI  - Effect of acute coronary occlusion on the size of the dynamically perfused
      coronary capillary bed in the dog.
AB  - The aim of the present study was to investigate the influence of reduced left
      anterior descending (LAD) coronary arterial blood flow on the size of the
      perfused coronary capillary surface area (CCSA) in dogs. The transcoronary
      hydrolysis (v) of the specific ACE substrate, [3H]benzoyl-Phe-Ala-Pro, was
      estimated and the parameter Amax/Km (proportional to the size of the perfused
      CCSA) was calculated. By means of a ligature placed around the LAD, LAD blood
      flow was transiently reduced to 36.0 +/- 4.1 (E1) and 17.4 +/- 4.3% (E2) of
      control; in a separate maneuver the first diagonal branch of the LAD was ligated
      to achieve 40.0 +/- 6.7% (E3) of control flow. The v values remained unchanged at
      around 0.7 for E1, E2, and E3 determinations, suggesting unaltered substrate
      transit time through the coronary capillary bed. Amax/Km values decreased to 36
      +/- 5, 17 +/- 4, and 47 +/- 10% of control for E1, E2, and E3 determinations,
      respectively, reflecting a flow-proportional decrease in CCSA. Values of the
      transpulmonary measures of v and Amax/Km performed at the beginning and end of
      the protocol were unchanged. These results support the hypothesis that reduction
      in coronary blood flow will produce proportional decreases in the size of the
      CCSA. This new procedure can thus serve as a useful tool for investigating
      alterations in the size of the CCSA in different species and under various
      pathophysiologic challenges.

PMID- 9756733
TI  - Dynamic changes in intracapillary hemoglobin oxygenation in human skin following
      various temperature changes.
AB  - To evaluate microvascular regulation in human skin, changes in intracapillary
      hemoglobin oxygen saturation (HbO2) were studied in human finger skin following
      an abrupt change in local ambient temperature. In the first series of
      experiments, we assessed the heterogeneity of HbO2 in the skin by using a 2-D
      scanning system and a rapid micro-lightguide spectrophotometer at each of two
      near-normal skin temperatures. The data showed that heterogeneous oxygenation
      exists in human skin even at near-normal temperatures (although the pattern is
      different at different skin temperatures). In a second series of experiments, the
      performance of the microcirculation of the skin was continuously examined in a
      selected area with initially different oxygenation levels during an abrupt change
      in local ambient temperature (5, 15, 25, 35, and 45 degrees C). At very low (5
      degrees C) or very high (45 degrees C) temperatures, oxygenation in tissues
      within the low HbO2 area increased greatly, but there was no such change within
      the high HbO2 area. Our data indicate that different types of capillary supply
      units exist in human skin (indicated by the initially different oxygenation
      levels). These different capillary supply units may operate to produce a local
      redistribution of flow between the various capillary supply units. This effect
      may be initiated by heat sensors and oxygen sensors when temperature of the skin
      is varied.

PMID- 9756734
TI  - Prediction of microcirculatory oxygen transport by erythrocyte/hemoglobin
      solution mixtures.
AB  - A mathematical model has been developed to predict oxygen transport by
      erythrocyte/acellular hemoglobin solution mixtures flowing in arteriolar-sized
      vessels (20 to 100 micron diameter). The model includes erythrocyte and
      extracellular hemoglobin solution phases, radial hematocrit and velocity
      gradients, axial convection, and radial diffusion of both oxygen and
      oxyhemoglobin. Model simulations were compared with experimental data from an in
      vitro capillary model where all of the geometric, physical, and transport
      parameters are known accurately. A new approach to shear augmentation of
      transport in 25-micron-diameter conduits was developed. Comparison of theory with
      experiment suggests that shear augmentation in this flow regime is primarily an
      extracellular phenomenon produced by cell-cell interactions. Negligible shear
      augmentation was seen in erythrocyte suspensions in plasma due to the relatively
      low solubility of oxygen in the plasma phase. Good agreement was found between
      the theoretical simulations and experimental data for release experiments even
      neglecting shear augmentation. However, treatment of shear augmentation
      significantly improved agreement between theoretical simulations and experimental
      data for oxygen uptake. The model was used to determine the effects on oxygen
      transport of varying extracellular hemoglobin concentration and extracellular
      hemoglobin oxygen binding characteristics. It is known that hemoglobin solutions
      transport oxygen more efficiently than erythrocyte suspensions of the same
      overall hemoglobin content. Model simulations show that erythrocyte/hemoglobin
      solution mixtures with 30% extracellular hemoglobin transport oxygen with
      virtually the same efficiency as pure hemoglobin solutions of the same overall
      hemoglobin content. Additional simulations predict that erythrocyte/hemoglobin
      solution mixtures transport oxygen more efficiently than Rbc suspensions, even if
      the extracellular hemoglobin has a high oxygen affinity.

PMID- 9756735
TI  - Pressure-volume relationships in sheep mesenteric lymphatic vessels in situ:
      response to hypovolemia.
AB  - We applied the principles of cardiac mechanics to study the contraction cycles of
      postnodal sheep mesenteric lymphatic vessels in an in situ preparation. A segment
      of intestinal lymphatic was isolated from lymph input and provided with Krebs
      solution from a reservoir. Pressure-volume relationships were assessed under
      various transmural pressure conditions using videomicroscopic techniques to
      measure diameter changes and a miniature catheter pressure transducer to monitor
      intralymphangion pressure. The contraction cycles were quite variable but, on
      average, exhibited three phases of systole and three phases of diastole with
      periods of isovolumetric contraction and relaxation. Elevations of transmural
      pressure up to 4 cm H2O resulted in significant increases in stroke volume,
      ejection fraction, pulse pressure, and output/minute but not contraction
      frequency. Regression analysis of the end systolic (ESPVR) and end diastolic
      pressure-volume relations (EDPVR) revealed a linear ESPVR (r2 = 0.83 +/- 0.03)
      and exponential EDPVR (r2 = 0.83 +/- 0.02), a result that is similar to that
      observed in cardiac contraction cycles. Following a 25% whole blood volume bleed
      (a stimulus known to enhance lymphatic pumping), significant increases in stroke
      volume, ejection fraction, and output/minute were observed up to transmural
      pressures of 4 cm H2O. While an index used to assess cardiac contractility (end
      systolic elastance-Ees) was not observed to change after the bleed, a shift to
      the left of the end-systolic pressure-volume relations compared with the sham
      bled group (significant shift of regression lines for ESPVR) suggested that
      hemorrhage exerted a positive inotropic effect on mesenteric lymphatics.

PMID- 9756737
TI  - Gender and Negotiator Competitiveness: A Meta-analysis.
AB  - Although there have been numerous investigations into the relationship between
      gender and bargaining competitiveness over the past several decades, few
      conclusions have been reached. The results of 62 research reports on the
      relationship between gender and competitive behavior in dyadic bargaining
      interactions were examined by meta-analytic review. The average weighted effect
      size indicated that women appear to behave more cooperatively in negotiations
      than men, but this difference is slight. Results suggest that constraints on
      negotiators (imposed by abstract bargaining paradigms and restrictions on
      communication) lessen gender differences in negotiation behavior. Women were
      significantly more competitive than men when competing against an opponent who
      pursued a "tit-for-tat" bargaining strategy. Copyright 1998 Academic Press.

PMID- 9756738
TI  - Decision Accuracy in Computer-Mediated versus Face-to-Face Decision-Making Teams.
AB  - Changes in the way organizations are structured and advances in communication
      technologies are two factors that have altered the conditions under which group
      decisions are made. Decisions are increasingly made by teams that have a
      hierarchical structure and whose members have different areas of expertise. In
      addition, many decisions are no longer made via strictly face-to-face
      interaction. The present study examines the effects of two modes of communication
      (face-to-face or computer-mediated) on the accuracy of teams' decisions. The
      teams are characterized by a hierarchical structure and their members differ in
      expertise consistent with the framework outlined in the Multilevel Theory of team
      decision making presented by Hollenbeck, Ilgen, Sego, Hedlund, Major, and
      Phillips (1995). Sixty-four four-person teams worked for 3 h on a computer
      simulation interacting either face-to-face (FtF) or over a computer network. The
      communication mode had mixed effects on team processes in that members of FtF
      teams were better informed and made recommendations that were more predictive of
      the correct team decision, but leaders of CM teams were better able to
      differentiate staff members on the quality of their decisions. Controlling for
      the negative impact of FtF communication on staff member differentiation
      increased the beneficial effect of the FtF mode on overall decision making
      accuracy. Copyright 1998 Academic Press.

PMID- 9756736
TI  - Direct relaxing effect of estradiol-17beta and progesterone on rat saphenous
      artery.
AB  - Although estrogen has been reported to relax large coronary arteries immediately,
      its direct acute effect on small vessel tone has not been fully defined. In this
      study, we investigated the effect of estradiol-17beta and progesterone on
      isolated rat saphenous artery segments-with an internal radius of 250 microm-by
      measuring the outer diameter of the vessels using in vitro angiometry. Estradiol
      and progesterone at concentrations of 1-100 and 8.6-86 microM induced a rapid,
      dose-dependent relaxation of the arterial segments precontracted with
      norepinephrine. Maximal changes of diameters were 85.8 +/- 10 and 90.9 +/- 8%.
      Clomiphene citrate, a cytoplasmic receptor antagonist, did not diminish this
      action of estradiol, with the exception of the highest concentrations of the
      hormone. Thus a nongenomic pathway for this effect can be suspected.
      Dexamethasone did not induce similar vasodilation. It is concluded that estradiol
      and progesterone have similar rapid vasorelaxing effects on small muscular
      arteries as found previously on coronary arteries.

PMID- 9756739
TI  - Effect of Regret on Post-choice Valuation: The Case of More Than Two
      Alternatives.
AB  - The author examines the influence of experienced regret on the selection of the
      reference point used in post-choice valuation. He incorporates two reference
      points, expected performance and performance of the forgone alternative, the
      former affecting the amount of satisfaction and the latter affecting the amount
      of regret experienced by a decision maker. Prior research on regret has assumed
      only a two-alternative choice set with the forgone alternative being the
      reference point for measuring regret. The author relaxes that assumption and
      develops hypotheses to examine the selection of the reference point in cases that
      more closely represent real-life experience (i.e., choice sets with more than two
      alternatives). Two studies are reported. The results from the first study support
      most of the hypotheses. The second study further investigated the selection of a
      reference point. Several theoretical and managerial implications are discussed
      and future research directions are suggested. Copyright 1998 Academic Press.

PMID- 9756740
TI  - Resource-Allocation Strategies: A Verbal Protocol Analysis.
AB  - The current study examined the strategies used by people to solve resource
      allocation problems. Verbal protocols were recorded as participants provided meal
      choices for seven consecutive days with limited resources available to spend on
      meals and with daily constraints imposed on meal consumption. None of the
      participants incorporated the established mathematical procedures (i.e., Linear
      Programming) to arrive at the optimum number of meals possible in a week.
      However, the strategies they did use enabled them to achieve meal totals on
      average at 94% of this optimal amount. A few participants attempted to first
      solve the maximum meals possible in a week before scheduling this solution across
      the seven days (solve-and-schedule strategy), but the majority of participants
      simply selected meals on a day-to-day basis while checking resource availability
      each day to allow for full resource consumption (consume-and-check strategy). The
      findings of this study provide a preliminary step toward understanding how people
      make intuitive resource-allocation decisions. Copyright 1998 Academic Press.

PMID- 9756741
TI  - Renaturation of recombinant human neurotrophin-3 from inclusion bodies using a
      suppressor agent of aggregation.
AB  - Escherichia coli has been widely used in the production of recombinant proteins.
      One of the drawbacks inherent in this method is that the proteins produced in the
      cells often form inactive inclusion bodies. Usually, the inclusion bodies can be
      separated from other cell components, solubilized by denaturants such as
      guanidine hydrochloride or urea, and then renatured through a refolding process
      such as dilution or dialysis. However, it has been shown that biologically active
      recombinant human neurotrophin-3 cannot be obtained at high yield by this
      procedure due to aggregation and precipitation of the protein. We applied the
      refolding process using the aggregation suppressor L-arginine in the renaturation
      of neurotrophin-3, and obtained biologically active neurotrophin-3 at high yield
      from the inclusion bodies. Consequently, about 10 mg of purified neurotrophin-3
      was prepared from 1 litre of culture broth.

PMID- 9756742
TI  - Recombinant human mast cell tryptase beta: stable expression in Pichia pastoris
      and purification of fully active enzyme.
AB  - Human mast cell tryptase beta (EC 3.4.21.59) is a trypsin-like serine protease
      that is stored in and released from mast cell granules. This enzyme has been
      expressed in Pichia pastoris via homologous recombination of the cDNA coding for
      the mature active tryptase with the addition of a KEX 2 processing site into the
      Pichia genome. Cells producing recombinant human tryptase (rHT) were selected by
      screening with antibodies. Induction with methanol resulted in the secretion of
      rHT into the Pichia growth medium; tryptase activity was stabilized by the
      addition of heparin to the culture medium. Increasing levels of enzyme were
      detected in the medium for up to 3 days. Fully active enzyme was purified from
      the culture medium with a 100% yield of activity via a simple two-step procedure,
      with hydrophobic interaction chromatography followed by affinity chromatography
      on immobilized heparin. Bands of 33 (faint), 34.2, 35.9 and 50 kDa (diffuse) were
      observed on SDS/PAGE. These multiple forms were due to differences in post
      translational glycosylation of asparagine residues, because enzymic
      deglycosylation resulted in only one band at 33 kDa. A single symmetrical peak
      with an estimated size of 197 kDa was obtained on gel filtration. Kinetic
      analyses in comparison with native human lung mast cell tryptase (HLT) yielded
      similar Km values, but the kcat of rHT was more than twice that of HLT.

PMID- 9756743
TI  - Granulocyte colony-stimulating factor and azole antifungal therapy in murine
      aspergillosis: role of immune suppression.
AB  - Outbred ICR mice were immune suppressed either with hydrocortisone or with 5
      fluorouracil and were infected intranasally with Aspergillus fumigatus. Beginning
      3 days before infection some groups of mice were given recombinant human
      granulocyte colony-stimulating factor (G-CSF), SCH56592 (an antifungal triazole),
      or both. Corticosteroid-pretreated mice responded to SCH56592 and had reduced
      counts in lung tissue and prolonged survival. In these mice, G-CSF strongly
      antagonized the antifungal activity of SCH56592. Animals treated with both agents
      developed large lung abscesses with polymorphonuclear leukocytes and large
      amounts of Aspergillus. In contrast, mice made neutropenic with 5-fluorouracil
      and then infected with A. fumigatus conidia benefited from either G-CSF or
      triazoles, and the effect of the combination was additive rather than
      antagonistic. Host predisposing factors contribute in different ways to the
      outcome of growth factor therapy in aspergillosis.

PMID- 9756744
TI  - Sequencing of gyrase and topoisomerase IV quinolone-resistance-determining
      regions of Chlamydia trachomatis and characterization of quinolone-resistant
      mutants obtained In vitro.
AB  - The L2 reference strain of Chlamydia trachomatis was exposed to subinhibitory
      concentrations of ofloxacin (0.5 microg/ml) and sparfloxacin (0.015 microg/ml) to
      select fluoroquinolone-resistant mutants. In this study, two resistant strains
      were isolated after four rounds of selection. The C. trachomatis mutants
      presented with high-level resistance to various fluoroquinolones, particularly to
      sparfloxacin, for which a 1,000-fold increase in the MICs for the mutant strains
      compared to the MIC for the susceptible strain was found. The MICs of unrelated
      antibiotics (doxycycline and erythromycin) for the mutant strains were identical
      to those for the reference strain. The gyrase (gyrA, gyrB) and topoisomerase IV
      (parC, parE) genes of the susceptible and resistant strains of C. trachomatis
      were partially sequenced. A point mutation was found in the gyrA quinolone
      resistance-determining region (QRDR) of both resistant strains, leading to a
      Ser83-->Ile substitution (Escherichia coli numbering) in the corresponding
      protein. The gyrB, parC, and parE QRDRs of the resistant strains were identical
      to those of the reference strain. These results suggest that in C. trachomatis,
      DNA gyrase is the primary target of ofloxacin and sparfloxacin.

PMID- 9756745
TI  - Restoration of immune response by a cationic amphiphilic drug (AY 9944) in vitro:
      a new approach To chemotherapy against human immunodeficiency virus type 1.
AB  - AY 9944 [AY; trans-1,4-bis(chlorobenzylaminomethyl)-cyclohexane dihydrochloride],
      an inhibitor of sterol synthesis, was found to help restore the normal mitogenic
      responses and cytokine profiles of peripheral mononuclear cells (PBMCs) from AIDS
      patients in vitro. Compared to untreated cells, the human immunodeficiency virus
      type 1 (HIV-1)-infected PBMCs precultured in the presence of AY exhibited a
      normal rate of either mitogen-induced or recall- and superantigen-induced
      proliferation. After 2 weeks in the presence of the drug, the percentage of dead
      CD4(+) cells in HIV-1-infected cultures was comparable to that observed in
      uninfected cultures, while over the same time interval it increased by three- to
      fivefold in HIV-1-infected cultures maintained in the absence of AY. AY also
      stimulated by 2- to 12-fold interleukin-12 (IL-12) and (gamma interferon
      production. For IL-12, this effect appears to be related to an increase in
      corresponding IL-12 p35 and IL-12 p40 mRNA levels. Moreover, AY restored the
      expression of the IL-2 receptor, which was severely impaired in HIV-1-infected
      PBMCs. Although the drug has no direct antiviral effect (it does not
      significantly inhibit reverse transcriptase activity measured in vitro), it might
      be considered a potential therapeutic agent for HIV-infected patients, in that it
      may correct viral infection-related immune system defects by indirectly enhancing
      the level of resistance to HIV and opportunistic infections.

PMID- 9756746
TI  - Mucoadhesive microspheres containing amoxicillin for clearance of Helicobacter
      pylori.
AB  - In an effort to augment the anti-Helicobacter pylori effect of amoxicillin,
      mucoadhesive microspheres, which have the ability to reside in the
      gastrointestinal tract for an extended period, were prepared. The microspheres
      contained the antimicrobial agent and an adhesive polymer (carboxyvinyl polymer)
      powder dispersed in waxy hydrogenated castor oil. The percentage of amoxicillin
      remaining in the stomach both 2 and 4 h after oral administration of the
      mucoadhesive microspheres to Mongolian gerbils under fed conditions was about
      three times higher than that after administration in the form of a 0.5%
      methylcellulose suspension. The in vivo clearance of H. pylori following oral
      administration of the mucoadhesive microspheres and the 0.5% methylcellulose
      suspension to infected Mongolian gerbils was examined under fed conditions. The
      mucoadhesive microspheres and the 0.5% methylcellulose suspension both showed
      anti-H. pylori effects in this experimental model of infection, but the required
      dose of amoxicillin was effectively reduced by a factor of 10 when the
      mucoadhesive microspheres were used. In conclusion, the mucoadhesive microspheres
      more effectively cleared H. pylori from the gastrointestinal tract than the 0.5%
      methylcellulose suspension due to the prolonged gastrointestinal residence time
      resulting from mucoadhesion. A dosage form consisting of mucoadhesive
      microspheres containing an appropriate antimicrobial agent should be useful for
      the eradication of H. pylori.

PMID- 9756747
TI  - Structure-in vitro activity relationships of pentamidine analogues and dication
      substituted bis-benzimidazoles as new antifungal agents.
AB  - Twenty analogues of pentamidine, 7 primary metabolites of pentamidine, and 30
      dicationic substituted bis-benzimidazoles were screened for their inhibitory and
      fungicidal activities against Candida albicans and Cryptococcus neoformans. A
      majority of the compounds had MICs at which 80% of the strains were inhibited
      (MIC80s) comparable to those of amphotericin B and fluconazole. Unlike
      fluconazole, many of these compounds were found to have potent fungicidal
      activity. The most potent compound against C. albicans had an MIC80 of </=0.09
      microg/ml, and the most potent compound against C. neoformans had an MIC80 of
      0.19 microg/ml. Selected compounds were also found to be active against
      Aspergillus fumigatus, Fusarium solani, Candida species other than C. albicans,
      and fluconazole-resistant strains of C. albicans and C. neoformans. It is clear
      from the data presented here that further studies on the structure-activity
      relationships, mechanisms of action and toxicities, and in vivo efficacies of
      these compounds are warranted to determine their clinical potential.

PMID- 9756748
TI  - In vitro antifungal activities of a series of dication-substituted carbazoles,
      furans, and benzimidazoles.
AB  - Aromatic dicationic compounds possess antimicrobial activity against a wide range
      of eucaryotic pathogens, and in the present study an examination of the
      structures-functions of a series of compounds against fungi was performed. Sixty
      seven dicationic molecules were screened for their inhibitory and fungicidal
      activities against Candida albicans and Cryptococcus neoformans. The MICs of a
      large number of compounds were comparable to those of the standard antifungal
      drugs amphotericin B and fluconazole. Unlike fluconazole, potent inhibitory
      compounds in this series were found to have excellent fungicidal activities. The
      MIC of one of the most potent compounds against C. albicans was 0.39 microg/ml,
      and it was the most potent compound against C. neoformans (MIC, </=0.09
      microg/ml). Selected compounds were also found to be active against Aspergillus
      fumigatus, Fusarium solani, Candida species other than C. albicans, and
      fluconazole-resistant strains of C. albicans and C. neoformans. Since some of
      these compounds have been safely given to animals, these classes of molecules
      have the potential to be developed as antifungal agents.

PMID- 9756749
TI  - Intracellular delivery and antibacterial activity of gentamicin encapsulated in
      pH-sensitive liposomes.
AB  - Cell membranes are relatively impermeable to the antibiotic gentamicin, a factor
      that, along with the toxicity of gentamicin, precludes its use against many
      important intracellular bacterial infections. Liposomal encapsulation of this
      drug was used in order to achieve intracellular antibiotic delivery and therefore
      increase the drug's therapeutic activity against intracellular pathogens.
      Gentamicin encapsulation in several dipalmitoylphosphatidylcholine (DPPC) and pH
      sensitive dioleoylphosphatidylethanolamine (DOPE)-based carrier systems was
      characterized. To systematically test the antibacterial efficacies of these
      formulations, a tissue culture assay system was developed wherein murine
      macrophage-like J774A.1 cells were infected with bacteria and were then treated
      with encapsulated drug. Of these formulations, DOPE-N-succinyl-DOPE and DOPE-N
      glutaryl-DOPE (70:30;mol:mol) containing small amounts of polyethyleneglycol
      ceramide showed appreciable antibacterial activities, killing greater than 75% of
      intracellular vacuole-resident wild-type Salmonella typhimurium compared to the
      level of killing of the control formulations. These formulations also efficiently
      eliminated intracellular infections caused by a recombinant hemolysin-expressing
      S. typhimurium strain and a Listeria monocytogenes strain, both of which escape
      the vacuole and reside in the cytoplasm. Control non-pH-sensitive liposomal
      formulations of gentamicin had poor antibacterial activities. A fluorescence
      resonance energy transfer assay indicated that the efficacious formulations
      undergo a pH-dependent lipid mixing and fusion event. Intracellular delivery of
      the fluorescent molecules encapsulated in these formulations was confirmed by
      confocal fluorescence microscopy and was shown to be dependent on endosomal
      acidification. This work shows that encapsulation of membrane-impermeative
      antibiotics in appropriately designed lipid-based delivery systems can enable
      their use in treating intracellular infections and details the development of a
      general assay for testing the intracellular delivery of encapsulated drug
      formulations.

PMID- 9756750
TI  - Interaction of Streptococcus pneumoniae and Moraxella catarrhalis: investigation
      of the indirect pathogenic role of beta-lactamase-producing moraxellae by use of
      a continuous-culture biofilm system.
AB  - The majority of clinical isolates of Moraxella catarrhalis produce beta
      lactamase. The role of this enzyme in the phenomenon of indirect pathogenicity,
      in which a true pathogen such as Streptococcus pneumoniae is protected from the
      action of certain beta-lactam antibiotics, is well recognized. By using a simple
      continuous-culture biofilm system, it has been shown that the pneumococcus
      attains high titers in excess of 10(12) CFU/biofilm; furthermore, the penicillin
      sensitive pneumococcus used remained susceptible to a range of beta-lactam
      antibiotics in these biofilms (R. K. Budhani and J. K. Struthers, J. Antimicrob.
      Chemother. 40:601-602, 1997). This system was used to characterize the antibiotic
      susceptibility of this isolate when grown with beta-lactamase-negative or 
      positive moraxellae. When grown with beta-lactamase-producing moraxellae in the
      presence of either benzylpenicillin or amoxicillin, the pneumococcus was
      protected in the range of the antibiotic concentrations to which it would be
      considered resistant. With amoxicillin-clavulanic acid the titers of the two
      organisms collapsed at the antibiotic concentration at which moraxellae became
      susceptible. The levels of beta-lactamase activity in cell-free supernatants of
      broth culture, in biofilm, and in biofilm effluent revealed distinct differences
      in this activity; levels in biofilm were significantly lower than those in broth
      culture supernatants. The system appears suitable for studying organisms under
      antibiotic stress and for investigating the interactions of bacteria under such
      conditions.

PMID- 9756751
TI  - Reduction by cefodizime of the pulmonary inflammatory response induced by heat
      killed Streptococcus pneumoniae in mice.
AB  - It has recently become apparent that overwhelming inflammatory reactions
      contribute to the high mortality rate associated with pneumococcal infection in
      immunocompetent hosts. Cefodizime (CEF) is an antibiotic that seems to be endowed
      with immunomodulating properties. To investigate the influence of CEF on the
      pulmonary inflammatory response induced by Streptococcus pneumoniae, we infected
      mice with repeated intranasal inoculations of 10(7) CFU of heat-killed
      fluorescein isothiocyanate-labeled bacteria, which are insensitive to the killing
      properties of the drug. CEF downregulated but did not abolish the strong
      polymorphonuclear leukocyte (PMN) recruitment induced by S. pneumoniae. PMN
      recruitment was not primarily mediated by leukotriene B4 in this model. The drug
      did not interfere with intrinsic mechanisms of phagocytosis by PMNs and alveolar
      macrophages. CEF totally abrogated the pneumococcus-induced tumor necrosis factor
      alpha (TNF-alpha) and interleukin-6 (IL-6) secretion in bronchoalveolar lavage
      fluid. The drug also prevented IL-6 release in lung homogenates and partly
      inhibited TNF-alpha, but it did not interfere with IL-1alpha secretion in the
      lungs of infected mice. The fractional and selective downregulation of
      inflammatory cells and cytokines by CEF suggests cell-specific and intracellular
      specific mechanisms of interaction of the drug. The immunomodulatory properties
      of CEF may help restrain excessive inflammatory reactions, thus contributing to
      the reported good clinical efficacy of the drug against lower respiratory tract
      infections.

PMID- 9756752
TI  - Identification and characterization of novel antimicrobial decapeptides generated
      by combinatorial chemistry.
AB  - Novel combinatorial libraries consisting of simplified amino acid sequences were
      designed to screen for peptides active against the Candida albicans membrane. A
      novel decapeptide, KKVVFKVKFK, that had a unique primary amino acid sequence was
      identified in this work. This peptide irreversibly inhibited the growth of C.
      albicans and showed a broad range of antibacterial activity but no hemolytic
      activity. Circular dichroism spectra revealed that the predominant secondary
      structure of this peptide strongly depended on the membrane-mimetic environments;
      the peptide preferred to form an amphipathic alpha-helical structure in the
      presence of 50% trifluoroethanol, while it preferred to adopt a distorted alpha
      helical structure in the presence of sodium dodecyl sulfate micelles. Experiments
      in which dye was released from vesicles indicated that this novel antimicrobial
      peptide killed microorganisms through the action on the membrane as its primary
      target. Replacement of amino acids in this active decapeptide on the basis of
      information from the libraries could provide unique information about factors
      affecting its antimicrobial activity such as its secondary structure, net
      positive charge, and hydrophobicity.

PMID- 9756753
TI  - Efficacies of KY62 against Leishmania amazonensis and Leishmania donovani in
      experimental murine cutaneous leishmaniasis and visceral leishmaniasis.
AB  - Current therapy for leishmaniasis is unsatisfactory because parenteral antimonial
      salts and pentamidine are associated with significant toxicity and failure rates.
      We examined the efficacy of KY62, a new, water-soluble, polyene antifungal,
      against cutaneous infection with Leishmania amazonensis and against visceral
      infection with Leishmania donovani in susceptible BALB/c mice. Mice were infected
      with L. amazonensis promastigotes in the ear pinna and in the tail and were
      treated with KY62 or amphotericin B. The cutaneous lesions showed a remarkable
      response to therapy with KY62 at a dose of 30 mg per kg of body weight per day.
      At this dose, the efficacy of KY62 was equivalent to or better than that of
      amphotericin B at 1 to 5 mg/kg/day. Mice infected intravenously with 10(7) L.
      donovani promastigotes and treated with KY62 showed a 4-log reduction in the
      parasite burden in the liver and spleen compared to untreated mice. These studies
      indicate potent activity of KY62 against experimental cutaneous leishmaniasis
      caused by L. amazoniensis and against experimental visceral leishmaniasis caused
      by L. donovani.

PMID- 9756755
TI  - Characterization of In40 of Enterobacter aerogenes BM2688, a class 1 integron
      with two new gene cassettes, cmlA2 and qacF.
AB  - Enterobacter aerogenes BM2688, which is resistant to multiple antibiotics, and
      its aminoglycoside-susceptible derivative BM2688-1 were isolated from the same
      clinical sample. Strain BM2688 harbored plasmid pIP833, which carries a class 1
      integron, In40, containing (in addition to qacEDelta1 and sul1, which are
      characteristic of class 1 integrons) four gene cassettes: aac(6')-Ib, qacF,
      cmlA2, and oxa-9. The cmlA2 gene had 83.7% identity with the previously described
      nonenzymatic chloramphenicol resistance cmlA1 gene. The qacF gene conferred
      resistance to quaternary ammonium compounds and displayed a high degree of
      similarity with qacE (67.8% identity) which, however, has been found as part of a
      cassette with a very different 59-base element. The oxa-9 gene was not expressed
      due to a lack of promoter sequences. Study of the antibiotic-susceptible
      derivative BM2688-1 indicated that a 3,148-bp deletion between the 3' end of the
      aac(6')-Ib gene and the 3' conserved segment of In40 was responsible for the loss
      of resistance. The occurrence of this DNA rearrangement, which did not involve
      homologous sequences, suggests that the In40 integrase could promote
      recombination at secondary sites.

PMID- 9756754
TI  - Interleukin-12 enhances in vivo parasiticidal effect of benznidazole during acute
      experimental infection with a naturally drug-resistant strain of Trypanosoma
      cruzi.
AB  - The roles of gamma interferon (IFN-gamma) and interleukin-12 (IL-12) in mediating
      and/or enhancing the in vivo trypanosomicidal activity of the nitroheterocyclic
      derivative benznidazole (Bz) were evaluated during early stages of experimental
      Chagas' disease. Our results show that treatment of Trypanosoma cruzi-infected
      mice with anti-cytokine monoclonal antibodies (MAbs) had no apparent effect when
      the optimal dose of Bz (100 mg/kg of body weight) was used. In contrast,
      treatment with anti-IL-12 or anti-IFN-gamma MAbs enhanced the parasitemia and
      accelerated the mortality of mice treated with a suboptimal dose of Bz (25
      mg/kg). Simultaneous treatment with a suboptimal dose of Bz and recombinant IL-12
      (rIL-12) enhanced the efficacy of drug treatment in terms of parasitemia and
      mouse survival. Interestingly, we found that drug-resistant T. cruzi strains were
      found to be poor inducers of IL-12 both in vitro and in vivo compared to strains
      of T. cruzi which are susceptible or partially resistant to Bz treatment. These
      results suggest that early activation of the cellular compartment of the immune
      system by IL-12 may favor in vivo Bz activity against T. cruzi. In order to test
      this hypothesis mice infected with the drug-resistant Colombiana strain of T.
      cruzi were treated with 100 mg of Bz per kg plus different concentrations of rIL
      12. By using the results of PCR and serological and parasitological methods as
      the criteria of a cure, our results indicate that a higher percentage of mice
      treated with Bz combined with rIL-12 than mice treated with Bz alone are cured.

PMID- 9756756
TI  - Comparison of inhibitory and bactericidal activities and postantibiotic effects
      of LY333328 and ampicillin used singly and in combination against vancomycin
      resistant Enterococcus faecium.
AB  - One hundred ninety-five individual vancomycin-resistant Enterococcus faecium
      (VRE) isolates from five upstate New York hospitals were studied for
      antimicrobial susceptibilities to LY333328, quinupristin-dalfopristin,
      teicoplanin, ampicillin, and gentamicin. LY333328 was the most active antibiotic
      against VRE. The effect of media and methods on the antibacterial activity of
      LY333328, its synergy with ampicillin, and the postantibiotic effects (PAE) of
      LY333328 and ampicillin were evaluated. In microdilution tests, the MIC of
      LY333328 at which 90% of the isolates were inhibited (MIC90) was 2 microg/ml in
      Mueller-Hinton II (MH II) broth and 1 microg/ml in brain heart infusion (BHI)
      broth. In contrast, on MH II agar the MIC90 was 4 microg/ml and on BHI agar it
      was >16 microg/ml. Bactericidal activity was observed for most strains at
      concentrations from 8 to >/=133 times the MIC of the tube macrodilution in MH II
      broth. A bactericidal effect of LY333328 plus ampicillin was demonstrated in time
      kill studies, but there was great strain-to-strain variability. By the MH II agar
      dilution method, bacteristatic synergy (defined as a fractional inhibitory
      concentration of <0.5) with LY333328 and ampicillin was demonstrated for 61% of
      the strains tested. Under similar conditions, there was synergy with LY333328 and
      quinupristin-dalfopristin or gentamicin for 27 and 15% of the strains tested,
      respectively. The PAE of LY333328 was prolonged (23.0 h at 10 times the MIC).
      However, 50% normal pooled human serum decreased the PAE to 12.2 h at 10 times
      the MIC. Test conditions and media had a considerable effect on VRE
      susceptibilities to LY333328. The prolonged PAE of LY333328, a potent new
      bactericidal glycopeptide, and its synergy with ampicillin in a large proportion
      of strains suggest that further evaluation of this drug in pharmacokinetic
      studies and experimental infections, including those with VRE, is warranted.

PMID- 9756757
TI  - Accumulation of amphotericin B in human macrophages enhances activity against
      Aspergillus fumigatus conidia: quantification of conidial kill at the single-cell
      level.
AB  - A cytofluorometric assay that allowed assessment of damage to phagocytosed
      Aspergillus fumigatus conidia at the single-cell level was developed. After
      ingestion by monocyte-derived macrophages (MDMs), conidia were reisolated by
      treatment of the cells with streptolysin O, a pore-forming toxin with lytic
      properties on mammalian cells but not on fungi. The counts obtained by staining
      of damaged conidia with propidium iodide and quantification by cytofluorometry
      correlated with colony counts. By the use of this method, we demonstrate that
      MDMs differentiated in vitro by low-dose granulocyte-macrophage colony
      stimulating factor and gamma interferon have only a limited capacity to damage
      Aspergillus conidia in vitro. The killing rate 12 h after phagocytosis was found
      to be only 10 to 15%. However, intracellular loading of the phagocytes with
      amphotericin B (AmB) dose dependently enhanced the anticonidial activity.
      Preincubation of macrophages with only 1 microg of AmB per ml resulted in an
      uptake of 18 fg of AmB/cell, leading to killing rates of 50 to 60%. The
      experimental protocol provides a new tool for the rapid quantification of
      anticonidial activity against A. fumigatus in vitro. Intracellular accumulation
      of AmB may represent an important factor underlying the efficacy of this
      antifungal drug in the prophylaxis and treatment of Aspergillus infections.

PMID- 9756758
TI  - Roles of amino acids 161 to 179 in the PSE-4 omega loop in substrate specificity
      and in resistance to ceftazidime.
AB  - The PSE-4 enzyme is a prototype carbenicillin-hydrolyzing enzyme exhibiting high
      activity against penicillins and early cephalosporins. To understand the
      mechanism that modulates substrate profiles and to verify the ability of PSE-4 to
      extend its substrate specificity toward expanded-spectrum cephalosporins, we used
      random replacement mutagenesis to generate six random libraries from amino acids
      162 to 179 in the Omega loop. This region is known from studies with TEM-1 to be
      implicated in substrate specificity. It was found that the mechanism modulating
      ceftazidime hydrolysis in PSE-4 was different from that in TEM-1. The specificity
      of class 2c carbenicillin-hydrolyzing enzymes could not be assigned to the Omega
      loop of PSE-4. Analysis of the percentage of functional enzymes revealed that the
      hydrolysis of ampicillin was more affected than hydrolysis of carbenicillin by
      amino acid substitutions at positions 162 to 164 and 165 to 167.

PMID- 9756759
TI  - Rapid, transient fluconazole resistance in Candida albicans is associated with
      increased mRNA levels of CDR.
AB  - Fluconazole-resistant Candida albicans, a cause of recurrent oropharyngeal
      candidiasis in patients with human immunodeficiency virus infection, has recently
      emerged as a cause of candidiasis in patients receiving cancer chemotherapy and
      marrow transplantation (MT). In this study, we performed detailed molecular
      analyses of a series of C. albicans isolates from an MT patient who developed
      disseminated candidiasis caused by an azole-resistant strain 2 weeks after
      initiation of fluconazole prophylaxis (K. A. Marr, T. C. White, J. A. H.
      vanBurik, and R. A. Bowden, Clin. Infect. Dis. 25:908-910, 1997). DNA sequence
      analysis of the gene (ERG11) for the azole target enzyme, lanosterol demethylase,
      revealed no difference between sensitive and resistant isolates. A sterol
      biosynthesis assay revealed no difference in sterol intermediates between the
      sensitive and resistant isolates. Northern blotting, performed to quantify mRNA
      levels of genes encoding enzymes in the ergosterol biosynthesis pathway (ERG7,
      ERG9, and ERG11) and genes encoding efflux pumps (MDR1, ABC1, YCF, and CDR),
      revealed that azole resistance in this series is associated with increased mRNA
      levels for members of the ATP binding cassette (ABC) transporter superfamily, CDR
      genes. Serial growth of resistant isolates in azole-free media resulted in an
      increased susceptibility to azole drugs and corresponding decreased mRNA levels
      for the CDR genes. These results suggest that C. albicans can become transiently
      resistant to azole drugs rapidly after exposure to fluconazole, in association
      with increased expression of ABC transporter efflux pumps.

PMID- 9756760
TI  - Characterization of mutations in the rpoB gene that confer rifampin resistance in
      Staphylococcus aureus.
AB  - Mutations in the rifampin resistance-determining (Rif) regions of the rpoB gene
      of Staphylococcus aureus mutants obtained during therapy or in vitro were
      analyzed by gene amplification and sequencing. Each of the resistant clinical
      isolates, including five nonrelated clones and two strains isolated from the same
      patient, and of the 10 in vitro mutants had a single base pair change that
      resulted in an amino acid substitution in the beta subunit of RNA polymerase.
      Eight mutational changes at seven positions were found in cluster I of the
      central Rif region. Certain substitutions (His481/Tyr and Asp471/Tyr [S. aureus
      coordinates]) were present in several mutants. Substitutions Gln468/Arg,
      His481/Tyr, and Arg484/His, which conferred high-level rifampin resistance, were
      identical or in the same codon as those described in other bacterial genera,
      whereas Asp550/Gly has not been reported previously. Substitutions at codon 477
      conferred high- or low-level resistance, depending on the nature of the new amino
      acid. The levels of resistance of in vivo and one-step in vitro mutants carrying
      identical mutations were similar, suggesting that no other resistance mechanism
      was present in the clinical isolates. On the basis of these data and the
      population distribution of more than 4,000 clinical S. aureus isolates, we
      propose </=0.5 and >/=8 microg/ml as new breakpoints for the clinical
      categorization of this species relative to rifampin.

PMID- 9756762
TI  - Stability of cephalosporin prodrug esters in human intestinal juice: implications
      for oral bioavailability.
AB  - The levels of degradation of cefetamet pivoxil (CAT), cefuroxime axetil (CAE),
      and cefpodoxime proxetil (CPD) in 0.6 M phosphate buffer (pH 7.4) and human
      intestinal juice (pH 7.4) at 37 degreesC over 24 h were compared. Significant
      differences in the time courses of degradation and in the patterns of degradation
      products were observed. (i) The relative proportions of the Delta2- and Delta3
      cephalosporins were roughly reversed in the two incubation media. In phosphate
      buffer, the major degradation product was the Delta2-cephalosporin (CAT = 61%;
      CAE = 74%; CPD = 85%), while in intestinal juice it was the Delta3-cephalosporin
      (CAT = 86%; CAE = 75%; CPD = 87%). (ii) Generally, the degradation of the prodrug
      esters progressed faster in intestinal juice than in phosphate buffer (e.g., for
      CAT the half-lives [t1/2s] were 0.78 and 4.3 h, respectively). (iii) The two
      diastereoisomers of CAE and CPD were degraded at different rates in intestinal
      juice (for the CAE diasteroisomers, t1/2s = 0.37 and 0.93 h; for the CPD
      diastereoisomers, t1/2s = 0.18 and 0.98 h) but were degraded at similar rates in
      phosphate buffer (for the CAE diastereoisomers, t1/2 = 1.6 h; for the CPD t1/2
      diastereoisomers, = 2.2 h). It is concluded that (i) the Delta2 isomerization
      does not significantly affect the bioavailability of prodrug esters since
      enzymatic hydrolysis in the intestinal fluid proceeds mainly to the active Delta3
      cephalosporin and (ii) the high degree of stereoselectivity of the enzymatic
      ester hydrolysis should make it possible to increase the bioavailabilities of
      certain prodrug esters (CAE, CPD) by using the more stable diasterioisomer.

PMID- 9756761
TI  - Targeted antimicrobial photochemotherapy.
AB  - This study explores a new approach for antimicrobial therapy with light
      activation of targeted poly-L-lysine (pL)-chlorin e6 (ce6) conjugates. The goal
      was to test the hypothesis that these conjugates between pL and ce6 would
      efficiently target photodestruction towards gram-positive (Actinomyces viscosus)
      and gram-negative (Porphyromonas gingivalis) oral species while sparing an oral
      epithelial cell line (HCPC-1). Conjugates of ce6 with pL (average molecular
      weight, 2,000) having a positive, neutral, or negative charge were prepared.
      Illumination with red light (lambdamax = 671 nm) from a diode array produced a
      dose-dependent loss of CFU from the bacteria, under conditions that did not
      affect the viability of the epithelial cells. For P. gingivalis, the cationic
      conjugate produced 99% killing, while the neutral conjugate killed 91% and the
      anionic conjugate killed 76% after 1 min of incubation and exposure to red light
      for 10 min. For A. viscosus, the cationic conjugate produced >99.99% killing
      while HCPC-1 cells remained intact. The importance of the positive charge was
      shown by the effectiveness of ce6-monoethylenediamine monoamide (a monocationic
      derivative of ce6) in killing both bacteria. The clinically employed
      benzoporphyrin derivative under the same conditions killed epithelial cells while
      leaving P. gingivalis relatively unharmed. A mixture of ce6 with pL did not show
      phototoxicity comparable with that of the cationic conjugate. These results were
      explained by the selective uptake of the conjugates by bacteria (20- to 100-fold)
      compared to that by mammalian cells, while free ce6 showed much less selectivity
      for bacteria (5- to 20-fold). The data suggest that the cationic pL-ce6 conjugate
      may have an application for the photodynamic therapy of periodontal disease.

PMID- 9756763
TI  - Secretion of sparfloxacin from the human intestinal Caco-2 cell line is altered
      by P-glycoprotein inhibitors.
AB  - The mechanism of intestinal secretion of the difluorinated quinolone sparfloxacin
      was investigated with the epithelial cell line Caco-2 and was compared to that of
      the P-glycoprotein (P-gp) substrate vinblastine. The P-gp inhibitors verapamil
      and progesterone significantly increased the epithelial cell accumulation of both
      vinblastine and sparfloxacin. This increase is likely to result from an
      inhibition of drug secretion since both vinblastine uptake and sparfloxacin
      uptake are known to proceed through a passive transmembrane diffusion. The
      unidirectional fluxes across cell monlayers grown on permeable filters indicated
      that a net secretion of sparfloxacin and vinblastine occurred across Caco-2
      cells. These secretions were significantly inhibited by the MDR-reversing agent
      verapamil. We conclude that the P-gp is likely to be involved in the intestinal
      elimination of the difluorinated quinolone sparfloxacin.

PMID- 9756764
TI  - Characterization of a glycosyl transferase inactivating macrolides, encoded by
      gimA from Streptomyces ambofaciens.
AB  - In Streptomyces ambofaciens, the producer of the macrolide antibiotic spiramycin,
      an open reading frame (ORF) was found downstream of srmA, a gene conferring
      resistance to spiramycin. The deduced product of this ORF had high degrees of
      similarity to Streptomyces lividans glycosyl transferase, which inactivates
      macrolides, and this ORF was called gimA. The cloned gimA gene was expressed in a
      susceptible host mutant of S. lividans devoid of any background macrolide
      inactivating glycosyl transferase activity. In the presence of UDP-glucose, cell
      extracts from this strain could inactivate various macrolides by glycosylation.
      Spiramycin was not inactivated but forocidin, a spiramycin precursor, was
      modified. In vivo studies showed that gimA could confer low levels of resistance
      to some macrolides. The spectrum of this resistance differs from the one
      conferred by a rRNA monomethylase, such as SrmA. In S. ambofaciens, gimA was
      inactivated by gene replacement, without any deleterious effect on the survival
      of the strain, even under spiramycin-producing conditions. But the overexpression
      of gimA led to a marked decrease in spiramycin production. Studies with extracts
      from wild-type and gimA-null mutant strains revealed the existence of another
      macrolide-inactivating glycosyl transferase activity with a different substrate
      specificity. This activity might compensate for the effect of gimA inactivation.

PMID- 9756765
TI  - An Escherichia coli system expressing human deoxyribonucleoside salvage enzymes
      for evaluation of potential antiproliferative nucleoside analogs.
AB  - Deoxyribonucleoside salvage in animal cells is mainly dependent on two cytosolic
      enzymes, thymidine kinase (TK1) and deoxycytidine kinase (dCK), while Escherichia
      coli expresses only one type of deoxynucleoside kinase, i.e., TK. A bacterial
      whole-cell system based on genetically modified E. coli was developed in which
      the relevant bacterial deoxypyrimidine metabolic enzymes were mutated, and the
      cDNA for human dCK or TK1 under the control of the lac promoter was introduced.
      The TK level in extract from induced bacteria with cDNA for human TK1 was found
      to be 20,000-fold higher than that in the parental strain, and for the strain
      with human dCK, the enzyme activity was 160-fold higher. The in vivo
      incorporation of deoxythymidine (Thd) and deoxycytidine (dCyd) into bacterial DNA
      by the two recombinant strains was 20 and 40 times higher, respectively, than
      that of the parental cells. A number of nucleoside analogs, including cytosine
      arabinoside, 5-fluoro-dCyd, difluoro-dCyd, and several 5-halogenated deoxyuridine
      analogs, were tested with the bacterial system, as well as with human T
      lymphoblast CEM cells. The results showed a close correlation between the
      inhibitory effects of several important cytostatic and antiviral analogs on the
      recombinant bacteria and the cellular system. Thus, E. coli expressing human
      salvage kinases is a rapid and convenient model system which may complement other
      screening methods in drug discovery projects.

PMID- 9756766
TI  - Rifampin concentrations in various compartments of the human brain: a novel
      method for determining drug levels in the cerebral extracellular space.
AB  - Antimicrobial therapy for brain infections is notoriously difficult because of
      the limited extent of knowledge about drug penetration into the brain. Therefore,
      we determined the penetration of rifampin into various compartments of the human
      brain, including the cerebral extracellular space (CES). Patients undergoing
      craniotomy for resection of primary brain tumors were given a standard dose of
      600 mg of rifampin intravenously before the operation. A microdialysis probe (10
      by 0.5 mm) was inserted into the cortex distantly from the resection and was
      perfused with two different rifampin solutions. Rifampin concentrations in the
      CES were calculated by the no-net-flux method. Intraoperatively, samples were
      taken from brain tumor tissue, perifocal tissue, and normal brain tissue in the
      case of pole resections. Rifampin concentrations in the various samples were
      determined by using a bioassay with Sarcinea lutea. In the various compartments,
      rifampin concentrations were highest within tumors (1.37 +/- 1.34 microg/ml; n =
      8), followed by the perifocal region (0.62 +/- 0.67 microg/ml; n = 8), the CES
      (0.32 +/- 0.11 microg/ml; n = 6), and normal brain tissue (0.29 +/- 0.15
      microg/ml; n = 7). Rifampin concentrations in brain tumors do not adequately
      reflect concentrations in normal brain tissue or in the CES. Rifampin
      concentrations in the CES, as determined by microdialysis, are the most
      reproducible, and the least scattered, of the values for all compartments
      evaluated. Rifampin concentrations in all compartments exceed the MIC for
      staphylococci and streptococci. However, CES concentrations may be below the MICs
      for some mycobacterial strains.

PMID- 9756767
TI  - In vitro and in vivo efficacy of the triazole TAK-187 against Cryptococcus
      neoformans.
AB  - Multiple isolates of Cryptococcus neoformans, including those with fluconazole
      resistance, were tested to assess the in vitro activity of the new triazole TAK
      187. MICs of TAK-187 were at least eightfold lower than those of fluconazole, and
      fungicidal concentrations for most isolates were 4 microg/ml or less. TAK-187
      also was evaluated as intermittent therapy using two dosages in a rabbit model of
      experimental cryptococcal meningitis. Compared to daily treatment with
      fluconazole, as little as two doses of TAK-187 given 7 days apart were found to
      be effective. Plasma and cerebrospinal fluid TAK-187 concentrations were many
      times higher than MICs and fungicidal concentrations. Based upon its therapeutic
      efficacy and long half-life in the rabbit model, TAK-187 should be investigated
      for intermittent dosing in treatment or suppression of cryptococcal infections in
      humans.

PMID- 9756768
TI  - Antibiotic susceptibility patterns of Streptococcus pneumoniae in china and
      comparison of MICs by agar dilution and E-test methods.
AB  - Beta-lactam resistance by Streptococcus pneumoniae is becoming a significant
      threat to public health worldwide. However, data concerning antibiotic
      susceptibility patterns in China have not been published. In this study, a total
      of 79 clinical isolates and 244 nasopharyngeal isolates of S. pneumoniae were
      recovered between June and November 1997 in Beijing. The agreement between the
      MICs (+/-1 log2 dilution) of penicillin and ceftriaxone obtained by the agar
      dilution and E-test methods for the 79 clinical strains was very good (97.5 and
      93.7%, respectively). Of these 79 strains, 9 (11.4%) were intermediate and 2
      (2.5%) were resistant to penicillin. Of the 244 nasopharyngeal strains, 32
      (13.1%) were intermediate and 3 (1. 2%) were resistant to penicillin. The total
      of 277 penicillin-susceptible clinical and nasopharyngeal isolates of
      Streptococcus pneumoniae were 100% susceptible to amoxicillin-clavulanic acid,
      cefuroxime, ceftriaxone, and cefotaxime. In the 35 penicillin-intermediate and 
      resistant nasopharyngeal strains, elevated MICs of amoxicillin-clavulanic acid,
      cefuroxime, ceftriaxone, and cefotaxime were seen for </=4 isolates. Of 244
      nasopharyngeal isolates, the overall percentages of tetracycline, erythromycin,
      chloramphenicol, ofloxacin, and trimethoprim-sulfamethoxazole resistance were
      87.6, 74.0, 47.8, 3.7 and 63.3, respectively. Vancomycin and rifampin resistance
      were not detected. These findings demonstrate that the rate of penicillin
      resistant pneumococci is relatively low in China compared to those of other Asian
      countries. Resistance to non-beta-lactams was much higher than to beta-lactams.
      The E-test and agar dilution methods appeared to be comparable in identifying
      resistant strains.

PMID- 9756769
TI  - Genotypic and phenotypic characterization of human immunodeficiency virus type 1
      variants isolated from patients treated with the protease inhibitor nelfinavir.
AB  - Nelfinavir mesylate (formerly AG1343) is a potent and selective inhibitor of
      human immunodeficiency virus (HIV) protease approved for the treatment of
      individuals infected with HIV. Nucleotide sequence analysis of protease genes
      from plasma HIV type 1 (HIV-1) RNA revealed a unique aspartic acid (D)-to
      asparagine (N) substitution at residue 30 (D30N) in 25 of 55 patients treated
      with nelfinavir for a median of 13 weeks. Although the appearance of D30N was
      occasionally associated with concurrent or sequential emergence of other changes
      (e.g., at residues 35, 36, 46, 71, 77, and 88), genotypic changes associated with
      phenotypic resistance to other protease inhibitors were not observed (e.g., at
      residues 48, 50, 82, and 84) or were only rarely observed (e.g., at residue 90).
      In phenotypic assays, viral isolates with high-level resistance to nelfinavir
      remained susceptible to indinavir, saquinavir, ritonavir, and amprenavir
      (formerly VX-478/141W94). Similar results were observed in phenotypic assays
      utilizing HIV-1 NL4-3, which contained the D30N substitution alone or in
      combination with substitutions at other residues (e.g., residues 46, 71, and 88).
      These data indicate that the initial pathway of resistance to nelfinavir is
      unique and suggest that individuals failing short courses of nelfinavir
      containing regimens may respond to regimens containing other protease inhibitors.

PMID- 9756770
TI  - Mechanism of fluconazole resistance in Candida krusei.
AB  - The mechanisms of fluconazole resistance in three clinical isolates of Candida
      krusei were investigated. Analysis of sterols of organisms grown in the absence
      and presence of fluconazole demonstrated that the predominant sterol of C. krusei
      is ergosterol and that fluconazole inhibits 14alpha-demethylase in this organism.
      The 14alpha-demethylase activity in cell extracts of C. krusei was 16- to 46-fold
      more resistant to inhibition by fluconazole than was 14alpha-demethylase activity
      in cell extracts of two fluconazole-susceptible strains of Candida albicans.
      Comparing the carbon monoxide difference spectra of microsomes from C. krusei
      with those of microsomes from C. albicans indicated that the total cytochrome P
      450 content of C. krusei is similar to that of C. albicans. The Soret absorption
      maximum in these spectra was located at 448 nm for C. krusei and at 450 nm for C.
      albicans. Finally, the fluconazole accumulation of two of the C. krusei isolates
      was similar to if not greater than that of C. albicans. Thus, there are
      significant qualitative differences between the 14alpha-demethylase of C.
      albicans and C. krusei. In addition, fluconazole resistance in these strains of
      C. krusei appears to be mediated predominantly by a reduced susceptibility of
      14alpha-demethylase to inhibition by this drug.

PMID- 9756771
TI  - Pharmacodynamics of gatifloxacin in cerebrospinal fluid in experimental
      cephalosporin-resistant pneumococcal meningitis.
AB  - The purpose of this study was to evaluate the cerebrospinal fluid (CSF)
      pharmacodynamics of a new fluoroquinolone, gatifloxacin (AM-1155), in
      experimental pneumococcal meningitis. The penetration of gatifloxacin into CSF,
      calculated as the percentage of the area under the concentration-time curve (AUC)
      in CSF over the AUC in blood, was 46 to 56%. Gatifloxacin showed linear
      pharmacokinetics in CSF, and 1 h after intravenous dosages of 7.5, 15, or 30
      mg/kg of body weight, peak CSF concentrations were 0.46 +/- 0.08 (mean +/-
      standard deviation), 0.94 +/- 0.16, and 1.84 +/- 0.5 microg/ml, respectively. The
      elimination half-life of gatifloxacin in CSF was 3. 8 to 5.6 h (compared with 2.7
      to 3.2 h in blood). There was a significant interrelationship among the highest
      measured values of gatifloxacin in blood and CSF/minimal bactericidal
      concentration (Cpeak/MBC), the time antibiotic concentrations exceeded the MBC (T
      > MBC), and AUC/MBC (r = 0.94); in single-dose experiments, each correlated
      significantly with the bacterial killing rate. Divided-dose regimens, resulting
      in greater T > MBC values but lower Cpeak/MBC ratios, were more effective in
      terms of bacterial clearance compared with corresponding single-dose regimens.
      Gatifloxacin therapy was as effective as currently recommended regimens (e.g., a
      combination of ceftriaxone and vancomycin) against this highly cephalosporin
      resistant pneumococcal strain. The bactericidal activity of gatifloxacin in CSF
      was closely related to the AUC/MBC ratio, but maximal activity was achieved only
      when drug concentrations exceeded the MBC for the entire dosing interval.

PMID- 9756772
TI  - Development of a new cartridge radioimmunoassay for determination of
      intracellular levels of lamivudine triphosphate in the peripheral blood
      mononuclear cells of human immunodeficiency virus-infected patients.
AB  - A new sensitive method for the measurement of lamivudine triphosphate (3TC-TP),
      the active intracellular metabolite of lamivudine in human cells in vivo, has
      been established. The procedure involves rapid separation of 3TC-TP by using Sep
      Pak cartridges, dephosphorylation to 3TC by using acid phosphatase, and
      measurement by radioimmunoassay using a newly developed anti-3TC serum. The
      radioimmunoassay had errors of less than 21% and a cross-reactivity of less than
      0.016% with a wide variety of other nucleoside analogs. The limit of quantitation
      of the assay for intracellular 3TC-TP was 0.195 ng/ml (0.212 pmol/10(6) cells),
      and a cell sample of only 4 million cells was ample for the assay. This
      procedure, combined with our previously developed method for measuring zidovudine
      (ZDV) metabolite levels, proved capable of measuring 3TC-TP, ZDV monophosphate
      (ZDV-MP) and ZDV triphosphate (ZDV-TP) in human immunodeficiency virus (HIV)
      infected subjects treated with combination 3TC and ZDV therapy. In seven
      subjects, intracellular 3TC-TP levels ranged from 2.21 to 7.29 pmol/10(6) cells,
      while intracellular ZDV-MP and ZDV-TP levels ranged from <0. 01 to 1.76 and 0.01
      to 0.07 pmol/10(6) cells, respectively. Concentrations of 3TC in plasma
      determined in these subjects ranged from 0.34 to 9.40 microM, which was about
      fivefold higher than ZDV levels in plasma of 0.04 to 1.4 microM. This is the
      first study to determine the intracellular levels of the active metabolites in
      HIV-infected subjects treated with this combination. These methods should prove
      very useful for in vivo pharmacodynamic studies of combination therapy.

PMID- 9756773
TI  - gyrA mutations associated with fluoroquinolone resistance in eight species of
      Enterobacteriaceae.
AB  - Fluoroquinolone resistance (FQ-R) in clinical isolates of Enterobacteriaceae
      species has been reported with increasing frequency in recent years. Two
      mechanisms of FQ-R have been identified in gram-negative organisms: mutations in
      DNA gyrase and reduced intracellular drug accumulation. A single point mutation
      in gyrA has been shown to reduce susceptibility to fluoroquinolones. To determine
      the extent of gyrA mutations associated with FQ-R in enteric bacteria, one set of
      oligonucleotide primers was selected from conserved sequences in the flanking
      regions of the quinolone resistance-determining regions (QRDR) of Escherichia
      coli and Klebsiella pneumoniae. This set of primers was used to amplify and
      sequence the QRDRs from 8 Enterobacteriaceae type strains and 60 fluoroquinolone
      resistant clinical isolates of Citrobacter freundii, Enterobacter aerogenes,
      Enterobacter cloacae, E. coli, K. pneumoniae, Klebsiella oxytoca, Providencia
      stuartii, and Serratia marcescens. Although similarity of the nucleotide
      sequences of seven species ranged from 80.8 to 93.3%, when compared with that of
      E. coli, the amino acid sequences of the gyrA QRDR were highly conserved.
      Conservative amino acid substitutions were detected in the QRDRs of the
      susceptible type strains of C. freundii, E. aerogenes, K. oxytoca (Ser-83 to
      Thr), and P. stuartii (Asp-87 to Glu). Strains with ciprofloxacin MICs of >2
      microg/ml expressed amino acid substitutions primarily at the Gly-81, Ser-83, or
      Asp-87 position. Fluoroquinolone MICs varied significantly for strains exhibiting
      identical gyrA mutations, indicating that alterations outside gyrA contribute to
      resistance. The type and position of amino acid alterations also differed among
      these six genera. High-level FQ-R frequently was associated with single gyrA
      mutations in all species of Enterobacteriaceae in this study except E. coli.

PMID- 9756774
TI  - Antiparasitic effects of the intra-Golgi transport inhibitor megalomicin.
AB  - The macrolide antibiotic megalomicin (MGM) has been shown to inhibit vesicular
      transport between the medial- and trans-Golgi, resulting in the undersialylation
      of cellular proteins (P. Bonay, S. Munro, M. Fresno, and B. Alarcon, J. Biol.
      Chem. 271:3719-3726, 1996). Due to the effects of MGM on the Golgi and on the
      replication of enveloped viruses, we decided to test whether it has any
      antiparasitic activity. The results showed that MGM has potent activity against
      the epimastigote stage of Trypanosoma cruzi, producing a 50% inhibitory
      concentration (IC50) of 0.2 microg/ml. Furthermore, MGM was also active against
      the intracellular replicative, amastigote form of T. cruzi, completely preventing
      its replication in infected murine LLC/MK2 macrophages at a dose of 5 microg/ml.
      Although less potent, MGM was also active against Trypanosoma brucei
      epimastigotes (IC50, 2 microg/ml) and Leishmania donovani and Leishmania major
      promastigotes (IC50, 3 and 8 microg/ml, respectively). MGM also blocked
      intracellular replication of the asexual stage of Plasmodium falciparum-infected
      erythrocytes at 1 microg/ml. Finally, MGM was active in an in vivo model,
      resulting in the complete protection of BALB/c mice from death caused by acute T.
      brucei infection and significantly reducing the parasitemia. These results
      suggest that MGM is a potential drug for the treatment of veterinary and human
      parasitic diseases.

PMID- 9756775
TI  - In vivo efficacy of ABT-255 against drug-sensitive and -resistant Mycobacterium
      tuberculosis strains.
AB  - Current therapy for pulmonary tuberculosis involves 6 months of treatment with
      isoniazid, pyrazinamide, rifampin, and ethambutol or streptomycin for reliable
      treatment efficacy. The long treatment period increases the probability of
      noncompliance, leading to the generation of multidrug-resistant isolates of
      Mycobacterium tuberculosis. A treatment option that significantly shortened the
      course of therapy, or a new class of antibacterial effective against drug
      resistant M. tuberculosis would be of value. ABT-255 is a novel 2-pyridone
      antibacterial agent which demonstrates in vitro potency and in vivo efficacy
      against drug-susceptible and drug-resistant M. tuberculosis strains. By the
      Alamar blue reduction technique, the MIC of ABT-255 against susceptible strains
      of M. tuberculosis ranged from 0.016 to 0.031 microg/ml. The MIC of ABT-255
      against rifampin- or ethambutol-resistant M. tuberculosis isolates was 0.031
      microg/ml. In a murine model of pulmonary tuberculosis, 4 weeks of oral ABT-255
      therapy produced a 2- to 5-log10 reduction in viable drug-susceptible M.
      tuberculosis counts from lung tissue. Against drug-resistant strains of M.
      tuberculosis, ABT-255 produced a 2- to 3-log10 reduction in viable bacterial
      counts from lung tissue. ABT-255 is a promising new antibacterial agent with
      activity against M. tuberculosis.

PMID- 9756776
TI  - Inhibitory activities of gatifloxacin (AM-1155), a newly developed
      fluoroquinolone, against bacterial and mammalian type II topoisomerases.
AB  - We determined the inhibitory activities of gatifloxacin against Staphylococcus
      aureus topoisomerase IV, Escherichia coli DNA gyrase, and HeLa cell topoisomerase
      II and compared them with those of several quinolones. The inhibitory activities
      of quinolones against these type II topoisomerases significantly correlated with
      their antibacterial activities or cytotoxicities (correlation coefficient [r] =
      0.926 for S. aureus, r = 0.972 for E. coli, and r = 0.648 for HeLa cells).
      Gatifloxacin possessed potent inhibitory activities against bacterial type II
      topoisomerases (50% inhibitory concentration [IC50] = 13.8 microg/ml for S.
      aureus topoisomerase IV; IC50 = 0.109 microg/ml for E. coli DNA gyrase) but the
      lowest activity against HeLa cell topoisomerase II (IC50 = 265 microg/ml) among
      the quinolones tested. There was also a significant correlation between the
      inhibitory activities of quinolones against S. aureus topoisomerase IV and those
      against E. coli DNA gyrase (r = 0.969). However, the inhibitory activity against
      HeLa cell topoisomerase II did not correlate with that against either bacterial
      enzyme. The IC50 of gatifloxacin for HeLa cell topoisomerase II was 19 and was
      more than 2,400 times higher than that for S. aureus topoisomerase IV and that
      for E. coli DNA gyrase. These ratios were higher than those for other quinolones,
      indicating that gatifloxacin possesses a higher selectivity for bacterial type II
      topoisomerases.

PMID- 9756777
TI  - Use of microsphere technology for targeted delivery of rifampin to Mycobacterium
      tuberculosis-infected macrophages.
AB  - Microsphere technology was used to develop formulations of rifampin for targeted
      delivery to host macrophages. These formulations were prepared by using
      biocompatible polymeric excipients of lactide and glycolide copolymers. Release
      characteristics were examined in vitro and also in two monocytic cell lines, the
      murine J774 and the human Mono Mac 6 cell lines. Bioassay assessment of cell
      culture supernatants from monocyte cell lines showed release of bioactive
      rifampin during a 7-day experimental period. Treatment of Mycobacterium
      tuberculosis H37Rv-infected monocyte cell lines with rifampin-loaded microspheres
      resulted in a significant decrease in numbers of CFU at 7 days following initial
      infection, even though only 8% of the microsphere-loaded rifampin was released.
      The levels of rifampin released from microsphere formulations within monocytes
      were more effective at reducing M. tuberculosis intracellular growth than
      equivalent doses of rifampin given as a free drug. These results demonstrate that
      rifampin-loaded microspheres can be formulated for effective sustained and
      targeted delivery to host macrophages.

PMID- 9756778
TI  - Haemophilus ducreyi is susceptible to protegrin.
AB  - Protegrins, potent antimicrobial peptides found in porcine leukocytes, have
      activity against the sexually transmitted pathogens Neisseria gonorrhoeae,
      Chlamydia trachomatis, and human immunodeficiency virus type 1. We tested
      synthetic protegrin 1 (PG-1) for activity against nine isolates of Haemophilus
      ducreyi, the etiologic agent of chancroid. The test organisms included CIP 542
      (the type strain), 35000HP (a human-passaged variant of 35000), 35000HP-RSM2 (an
      isogenic D-glycero-D-manno-heptosyltransferase mutant of 35000HP), and six
      clinical isolates. The isolates were epidemiologically unrelated, represented
      three HindIII ribotypes, and had varying antimicrobial resistance patterns. In
      bactericidal assays, five isolates were rapidly killed by synthetic PG-1. In
      radial diffusion assays, all nine isolates were exquisitely sensitive to PG-1.
      These data highlight the potential of protegrins for development as topical
      agents to prevent many sexually transmitted diseases, including chancroid.

PMID- 9756779
TI  - Translation elongation factor 2 is part of the target for a new family of
      antifungals.
AB  - Translation elongation factor 2 (EF2), which in Saccharomyces cerevisiae is
      expressed from the EFT1 and EFT2 genes, has been found to be targeted by a new
      family of highly specific antifungal compounds derived from the natural product
      sordarin. Two complementation groups of mutants resistant to the semisynthetic
      sordarin derivative GM193663 were found. The major one (21 members) consisted of
      isolates with mutations on EFT2. The minor one (four isolates) is currently being
      characterized but it is already known that resistance in this group is not due to
      mutations on EFT1, pointing to the complex structure of the functional target for
      these compounds. Mutations on EF2 clustered, forming a possible drug binding
      pocket on a three-dimensional model of EF2, and mutant cell extracts lost the
      capacity to bind to the inhibitors. This new family of antifungals holds the
      promise to be a much needed and potent addition to current antimicrobial
      treatments, as well as a useful tool for dissection of the elongation process in
      ribosomal protein synthesis.

PMID- 9756780
TI  - Compartmental pharmacokinetics and tissue drug distribution of the pradimicin
      derivative BMS 181184 in rabbits.
AB  - The pharmacokinetics of the antifungal pradimicin derivative BMS 181184 in plasma
      of normal, catheterized rabbits were characterized after single and multiple
      daily intravenous administrations of dosages of 10, 25, 50, or 150 mg/kg of body
      weight, and drug levels in tissues were assessed after multiple dosing.
      Concentrations of BMS 181184 were determined by a validated high-performance
      liquid chromatography method, and plasma data were modeled into a two-compartment
      open model. Across the investigated dosage range, BMS 181184 demonstrated
      nonlinear, dose-dependent kinetics with enhanced clearance, reciprocal shortening
      of elimination half-life, and an apparently expanding volume of distribution with
      increasing dosage. After single-dose administration, the mean peak plasma BMS
      181184 concentration (Cmax) ranged from 120 microg/ml at 10 mg/kg to 648
      microg/ml at 150 mg/kg; the area under the concentration-time curve from 0 to 24
      h (AUC0-24) ranged from 726 to 2,130 microg . h/ml, the volume of distribution
      ranged from 0.397 to 0.799 liter/kg, and the terminal half-life ranged from 4.99
      to 2.31 h, respectively (P < 0.005 to P < 0.001). No drug accumulation in plasma
      occurred after multiple daily dosing at 10, 25, or 50 mg/kg over 15 days,
      although mean elimination half-lives were slightly longer. Multiple daily dosing
      at 150 mg/kg was associated with enhanced total clearance and a significant
      decrease in AUC0-24 below the values obtained at 50 mg/kg (P < 0.01) and after
      single-dose administration of the same dosage (P < 0.05). Assessment of tissue
      BMS 181184 concentrations after multiple dosing over 16 days revealed substantial
      uptake in the lungs, liver, and spleen and, most notably, dose-dependent
      accumulation of the drug within the kidneys. These findings are indicative of
      dose- and time-dependent elimination of BMS 181184 from plasma and renal
      accumulation of the compound after multiple dosing.

PMID- 9756781
TI  - Single-dose pharmacokinetics of a pleconaril (VP63843) oral solution and effect
      of food.
AB  - Pleconaril is an orally active broad-spectrum antipicornaviral agent which
      demonstrates excellent penetration into the central nervous system, liver, and
      nasal epithelium. We report the results of a randomized two-way crossover study
      designed to characterize the disposition of a single dose (200 mg) of pleconaril
      oral solution in fed and fasting humans. Twelve healthy adult subjects (18.7 to
      39 years of age) participated in this study. Each subject received a single 200
      mg dose of pleconaril oral solution, both coadministered with a standard English
      breakfast and following a 10-h predose fast. There was a minimum 7-day washout
      period between pleconaril doses. Repeated blood samples (n = 10) were obtained
      over 24 h postdose, and the pleconaril level in plasma was quantified by gas
      chromatography. Plasma concentration-versus-time data were curve fitted for each
      subject by using a nonlinear weighted least-squares algorithm, and
      pharmacokinetic parameters were determined from the polyexponential estimates.
      Pleconaril disposition was best characterized by a one-compartment open model
      with first-order absorption. The apparent bioavailability of pleconaril oral
      solution was significantly increased with the administration of food. The area
      under the concentration-time curve and maximum concentration of pleconaril in
      plasma achieved following the standard English breakfast (i.e., 9.08 +/- 3.23
      mg/liter . h and 1.14 +/- 0.58 mg/liter, respectively) were 2.2- and 2.5-fold
      higher, respectively than those achieved in the fasting state (i.e., 4.08 +/-
      2.74 mg/liter . h and 0.46 +/- 0.30 mg/liter, respectively). Mean plasma
      pleconaril concentrations 12 h after a single 200-mg oral dose (fed, 0.25 +/- 0.2
      mg/liter; fasting, 0.11 +/- 0.10 mg/liter) in healthy adults remained greater
      than that required to inhibit more than 90% of the enteroviruses in cell culture
      (i.e., 0.07 mg/liter). To enhance the oral bioavailability of pleconaril,
      coadministration with a fat-containing meal is recommended.

PMID- 9756783
TI  - Antitrypanosomal activity of a new triazine derivative, SIPI 1029, In vitro and
      in model infections.
AB  - A recently developed diaminotriazine derivative [O,O'-bis(1, 2-dihydro-2,2
      tetramethylene-4,6-diamino-S-triazin-1-yl)-1, 6-hexanediol dihydrochloride; T-46;
      SIPI 1029] was examined for activity against African trypanosomes in in vitro and
      in vivo model systems. In vitro, SIPI 1029 was 50% inhibitory for growth of
      bloodstream trypomastigotes of four strains of Trypanosoma brucei brucei and
      Trypanosoma brucei rhodesiense at 0.15 to 2.15 nM (50% inhibitory
      concentrations). In in vivo mouse laboratory models of T. b. rhodesiense clinical
      isolate infections, SIPI 1029 was curative for 12 of 13 isolates at </=10 mg/kg
      of body weight/day for 3 days. In eight infections, a single dose was >/=60%
      curative, and in six of these, a dose of </=5 mg/kg was sufficient for >/=60%
      cure rates. A number of these isolates were resistant to the standard trypanocide
      melarsoprol (Arsobal) and/or the diamidines diminazene aceturate (Berenil) and
      pentamidine. SIPI 1029 was also curative in combination with DL-alpha
      difluoromethylornithine (Ornidyl) in a T. b. brucei central nervous system model
      infection. Some evidence of toxicity was found in dosage regimens of 10 mg/kg/day
      for 2 or 3 days in which deaths were observed in 6 of 65 animals given this
      dosage regimen. The activity of SIPI 1029 in this study indicates that this class
      of compounds (diaminotriazines) should be explored as leads for new human and
      veterinary trypanocides.

PMID- 9756782
TI  - Treatment of vancomycin-resistant Enterococcus faecium with RP 59500
      (quinupristin-dalfopristin) administered by intermittent or continuous infusion,
      alone or in combination with doxycycline, in an in vitro pharmacodynamic
      infection model with simulated endocardial vegetations.
AB  - Quinupristin-dalfopristin is a streptogramin antibiotic combination with activity
      against vancomycin-resistant Enterococcus faecium (VREF), but emergence of
      resistance has been recently reported. We studied the activity of quinupristin
      dalfopristin against two clinical strains of VREF (12311 and 12366) in an in
      vitro pharmacodynamic model with simulated endocardial vegetations (SEVs) to
      determine the potential for resistance selection and possible strategies for
      prevention. Baseline MICs/minimal bactericidal concentrations (microg/ml) for
      quinupristin-dalfopristin, quinupristin, dalfopristin, and doxycycline were
      0.25/2, 64/>512, 4/512, and 0.125/8 for VREF 12311 and 0.25/32, 128/>512, 2/128,
      and 0.25/16 for VREF 12366, respectively. Quinupristin-dalfopristin regimens had
      significantly less activity against VREF 12366 than VREF 12311. An 8-microg/ml
      simulated continuous infusion was the only bactericidal regimen with time to
      99.9% killing = 90 hours. The combination of quinupristin-dalfopristin every 8 h
      with doxycycline resulted in more killing compared to either drug alone.
      Quinupristin-dalfopristin-resistant mutants (MICs, 4 microg/ml; resistance
      proportion, approximately 4 x 10(-4)) emerged during the quinupristin
      dalfopristin monotherapies for both VREF strains. Resistance was unstable in VREF
      12311 and stable in VREF 12366. The 8-microg/ml continuous infusion or addition
      of doxycycline to quinupristin-dalfopristin prevented the emergence of resistance
      for both strains over the 96-h test period. These findings replicated the
      development of resistance reported in humans and emphasized bacterial factors
      (drug susceptibility, high inoculum, organism growth phase) and infectious
      conditions (penetration barriers) which could increase chances for clinical
      resistance. The combination of quinupristin-dalfopristin with doxycycline and the
      administration of quinupristin-dalfopristin as a high-dose continuous infusion
      warrant further study to determine their potential clinical utility.

PMID- 9756784
TI  - Visceral leishmaniasis in the BALB/c mouse: a comparison of the efficacy of a
      nonionic surfactant formulation of sodium stibogluconate with those of three
      proprietary formulations of amphotericin B.
AB  - In this study, treatment efficacies of a nonionic surfactant vesicle formulation
      of sodium stibogluconate (SSG-NIV) and of several formulations of amphotericin B
      were compared in a murine model of visceral leishmaniasis. Treatment with
      multiple doses of AmBisome, Abelcet, and Amphocil (total dose, 12.5 mg of
      amphotericin B/kg of body weight) resulted in a significant suppression of
      parasite burdens in liver (P < 0.0005) and spleen (P < 0.0005) compared with
      those of controls, with Abelcet having the lowest activity. Only AmBisome and
      Amphocil gave significant suppression of parasites in bone marrow (compared to
      control values, P < 0.005). In the acute-infection model, single-dose treatments
      of SSG-NIV (296 mg of SbV/kg), SSG solution (296 mg of SbV/kg), or AmBisome (8 mg
      of amphotericin B/kg) were equally effective against liver parasites (compared to
      control values, P < 0.0005). SSG-NIV and AmBisome treatment also significantly
      suppressed parasites in bone marrow and spleen (P < 0.005), with SSG-NIV
      treatment being more suppressive (>98% suppression in all three sites). Free-SSG
      treatment failed to suppress spleen or bone marrow parasites. Infection status
      influenced treatment outcome. In the chronic-infection model, the AmBisome single
      dose treatment was less effective in all three infection sites and the SSG-NIV
      single-dose treatment was less effective in the spleen. The results of this study
      suggest that the antileishmanial efficacy of SSG-NIV compares favorably with
      those of the novel amphotericin B formulations.

PMID- 9756785
TI  - In vitro activity of the echinocandin antifungal agent LY303,366 in comparison
      with itraconazole and amphotericin B against Aspergillus spp.
AB  - LY303,366 (LY) is a novel derivative of the echinocandin class of antifungal
      agents. The in vitro activities of LY, itraconazole (ITZ), and amphotericin B
      (AMB) were assessed against 60 Aspergillus isolates, including 35 isolates of A.
      fumigatus, eight isolates of A. terreus, eight isolates of A. flavus, eight
      isolates of A. niger and one isolate of A. nidulans. Four A. fumigatus isolates
      were resistant to ITZ. Susceptibility testing for all drugs was performed with a
      broth microdilution procedure. LY was tested in two media: antibiotic medium 3
      (AM3) and Casitone with 2% glucose (CAS) with an inoculum of 2 x 10(3) spores/ml.
      ITZ and AMB were tested in RPMI 1640 with 2% glucose with an inoculum of 1 x
      10(6) spores/ml. All tests were incubated at 37 degrees C for 48 h. A novel end
      point was used to determine a minimal effective concentration (MEC) for LY, i.
      e., almost complete inhibition of growth save a few tiny spherical colonies
      attached to the microplate. MICs were measured for ITZ and AMB with a no-growth
      end point. Ranges and geometric mean (GM) MECs were from 0.0018 to >0.5 and
      0.0039 mg/liter and from 0.0018 to >0.5 and 0.008 mg/liter for LY in AM3 and LY
      in CAS, respectively. Differences between species were apparent, with A. flavus
      being significantly less susceptible to LY than any other species tested with
      both media (P </= 0.05). Ranges and GM MICs were from 0.125 to >16 and 0.7
      mg/liter for ITZ and from 0.25 to 16 and 1.78 mg/liter for AMB. Minimal
      fungicidal concentrations (MFCs) were also determined for all drugs. GM MFCs were
      0.018, 0.09, 19.76, and 12.64 mg/liter for LY in AM3, LY in CAS, ITZ, and AMB,
      respectively. LY in AM3 and LY in CAS were fungicidal for 86.7 and 68% of
      isolates, respectively (98% killing). In comparison, ITZ and AMB were fungicidal
      for 35 and 70% of isolates, respectively (99.99% killing). A reproducibility
      study was performed on 20% of the isolates. For 12 isolates retested, the MEC or
      MIC was the same or was within 1 dilution of the original value for 11, 11, 10,
      and 9 isolates for LY in AM3, LY in CAS, ITZ, and AMB, respectively. In
      conclusion, LY seems to be a promising antifungal agent with excellent in vitro
      activity against Aspergillus spp.

PMID- 9756787
TI  - In vitro studies of pharmacodynamic properties of vancomycin against
      Staphylococcus aureus and Staphylococcus epidermidis.
AB  - The bactericidal activities of vancomycin against two reference strains and two
      clinical isolates of Staphylococcus aureus and Staphylococcus epidermidis were
      studied with five different concentrations ranging from 2x to 64x the MIC. The
      decrease in the numbers of CFU at 24 h was at least 3 log10 CFU/ml for all
      strains. No concentration-dependent killing was observed. The postantibiotic
      effect (PAE) was determined by obtaining viable counts for two of the reference
      strains, and the viable counts varied markedly: 1.2 h for S. aureus and 6.0 h for
      S. epidermidis. The determinations of the PAE, the postantibiotic sub-MIC effect
      (PA SME), and the sub-MIC effect (SME) for all strains were done with BioScreen
      C, a computerized incubator for bacteria. The PA SMEs were longer than the SMEs
      for all strains tested. A newly developed in vitro kinetic model was used to
      expose the bacteria to continuously decreasing concentrations of vancomycin. A
      filter prevented the loss of bacteria during the experiments. One reference
      strain each of S. aureus and S. epidermidis and two clinical isolates of S.
      aureus were exposed to an initial concentration of 10x the MIC of vancomycin with
      two different half-lives (t1/2s): 1 or 5 h. The post-MIC effect (PME) was
      calculated as the difference in time for the bacteria to grow 1 log10 CFU/ml from
      the numbers of CFU obtained at the time when the MIC was reached and the
      corresponding time for an unexposed control culture. The difference in PME
      between the strains was not as pronounced as that for the PAE. Furthermore, the
      PME was shorter when a t1/2 of 5 h (approximate terminal t1/2 in humans) was
      used. The PMEs at t1/2s of 1 and 5 h were 6.5 and 3.6 h, respectively, for S.
      aureus. The corresponding figures for S. epidermidis were 10.3 and less than 6 h.
      The shorter PMEs achieved with a t1/2 of 5 h and the lack of concentration
      dependent killing indicate that the time above the MIC is the parameter most
      important for the efficacy of vancomycin.

PMID- 9756786
TI  - Proteasome inhibitors block development of Plasmodium spp.
AB  - Proteasomes degrade most of the proteins inside eukaryotic cells, including
      transcription factors and regulators of cell cycle progression. Here we show that
      nanomolar concentrations of lactacystin, a specific irreversible inhibitor of the
      20S proteasome, inhibit development of the exoerythrocytic and erythrocytic
      stages of the malaria parasite. Although lactacystin-treated Plasmodium berghei
      sporozoites are still invasive, their development into exoerythrocytic forms
      (EEF) is inhibited in vitro and in vivo. Erythrocytic schizogony of P. falciparum
      in vitro is also profoundly inhibited when drug treatment of the synchronized
      parasites is prior, but not subsequent, to the initiation of DNA synthesis,
      suggesting that the inhibitory effect of lactacystin is cell cycle specific.
      Lactacystin reduces P. berghei parasitemia in rats, but the therapeutic index is
      very low. Along with other studies showing that lactacystin inhibits stage
      specific transformation in Trypanosoma and Entamoeba spp., these findings
      highlight the potential of proteasome inhibitors as drugs for the treatment of
      diseases caused by protozoan parasites.

PMID- 9756788
TI  - Enhancement of antimicrobial activity of neuropeptide Y by N-terminal truncation.
AB  - The activity of neuropeptide Y (NPY) against Candida albicans, which was revealed
      to be fungicidal, was enhanced significantly by the truncation of amino acid
      residues at the N terminus. The most active peptides (MICs, approximately 1
      microM) were about 10-fold more potent than the intact NPY (MIC, approximately 10
      microM). The enhancement was weakened by the replacement of the N terminus by
      negatively charged residues and/or acylation of the alpha-amino group. These
      results suggest that only the alpha-helical region of NPY is necessary for the
      antimicrobial activity and that the net charge of the peptide is important for
      the activity.

PMID- 9756789
TI  - In vitro susceptibility of Coxiella burnetii to trovafloxacin in comparison with
      susceptibilities to pefloxacin, ciprofloxacin, ofloxacin, doxycycline, and
      clarithromycin.
AB  - The antibiotic susceptibilities of eight Greek isolates of Coxiella burnetii to
      trovafloxacin were determined by the shell vial assay. MICs of trovafloxacin and
      ofloxacin ranged from 1 to 2 microg/ml, those of pefloxacin ranged from 1 to 4
      microg/ml, those of ciprofloxacin ranged from 4 to 8 microg/ml, those of
      doxycycline ranged from 1 to 2 microg/ml, and those of clarithromycin ranged from
      2 to 4 microg/ml. Trovafloxacin exhibited no activity against C. burnetii at 4
      microg/ml.

PMID- 9756790
TI  - Explaining the bias in the 23S rRNA gene mutations associated with clarithromycin
      resistance in clinical isolates of Helicobacter pylori.
AB  - A single point mutation in the 23S rRNA gene of Helicobacter pylori is known to
      confer resistance to clarithromycin. Most prevalent among clarithromycin
      resistant clinical H. pylori isolates are the mutations from A-2142 to G and A
      2143 to G in the 23S rRNA gene. The bias in the 23S rRNA gene mutations
      conferring clarithromycin resistance may result from the higher MIC, stability of
      resistance, and growth rate found for the strains with the above-mentioned
      mutations.

PMID- 9756791
TI  - In vitro activities of 15 antimicrobial agents against clinical isolates of South
      African enterococci.
AB  - The activities of a panel of currently available antibiotics and the
      investigational agents LY 333328, linezolid, CL 331,002, CL 329,998, moxifloxacin
      (BAY 12-8039), trovafloxacin, and quinupristin-dalfopristin against 274 clinical
      isolates of enterococci were determined. No vancomycin resistance or beta
      lactamase production was observed. Except for 12 isolates (all non-Enterococcus
      faecalis) showing reduced susceptibility to quinupristin-dalfopristin (MIC, >/=4
      microg/ml), the new agents exhibited promising in vitro antienterococcal
      activity.

PMID- 9756792
TI  - A new approach for early assessment of the epileptogenic potential of quinolones.
AB  - The epileptogenic potential of pefloxacin and norfloxacin, two quinolone
      antibiotics, was investigated in vivo in three different animal species by
      measuring drug concentrations in cerebrospinal fluid (CSF), which is part of the
      biophase, at the onset of convulsions. Interestingly, the pefloxacin-to
      norfloxacin concentration ratios in CSF were virtually constant across the
      species (7.0, 6.6, and 6.0 in mice, rats, and rabbits, respectively), suggesting
      that this approach could be used to predict the relative epileptogenic potential
      of quinolones in humans.

PMID- 9756793
TI  - Characterization of IS18, an element capable of activating the silent aac(6')-Ij
      gene of Acinetobacter sp. 13 strain BM2716 by transposition.
AB  - Insertion sequence IS18 was detected by analysis of the spontaneous
      aminoglycoside resistant mutant Acinetobacter sp. 13 strain BM2716-1. Insertion
      of the element upstream from the silent acetyltransferase gene aac(6')-Ij created
      a hybrid promoter that putatively accounts for the expression of the
      aminoglycoside resistance gene. The 1, 074-bp IS18 element contained partially
      matched (20 out of 26 bases) terminal inverted repeats, one of which overlapped
      the 3' end of a 935-bp open reading frame potentially encoding a protein related
      to the transposases of the IS30 family. IS18 was found in 6 out of 29 strains of
      Acinetobacter sp. 13 but not in 10 strains each of A. baumannii and A.
      haemolyticus.

PMID- 9756794
TI  - In vitro susceptibilities of Chlamydia pneumoniae strains recovered from
      atherosclerotic coronary arteries.
AB  - Chlamydia pneumoniae strains have been recovered from arteriosclerotic coronary
      arteries, but their antibiotic susceptibility profiles have not yet been
      examined. We report in vitro susceptibility data for five cardiovascular C.
      pneumoniae isolates. These strains did not differ significantly from respiratory
      strains in their patterns of susceptibility to azithromycin, erythromycin,
      roxithromycin, ofloxacin, doxycycline, rifampin, and penicillin G. Roxithromycin
      was the most active macrolide, and rifampin was the most effective drug overall.

PMID- 9756795
TI  - PMX-622 (polymyxin B-dextran 70) does not alter in vitro activities of 11
      antimicrobial agents.
AB  - Because of its capacity to neutralize the lethality of gram-negative bacterial
      endotoxic lipopolysaccharides, PMX-622 (polymyxin B bound to dextran 70) is being
      developed for possible adjunctive therapy of gram-negative sepsis. In this study,
      it was determined that the in vitro antimicrobial activity of PMX-622 was minimal
      and that it does not interfere with the in vitro antimicrobial activity of 11
      antibiotics commonly used to treat gram-negative infections.

PMID- 9756796
TI  - Description of two new isolates of Streptococcus pneumoniae in spain that are
      highly resistant to cefotaxime.
AB  - Two strains of Streptococcus pneumoniae isolated from sputum and bronchoalveolar
      samples with high-level resistance to cefotaxime (MIC = 8 to 16 microg/ml) are
      described. One of them, belonging to serogroup 19, was also highly resistant to
      penicillin (MIC = 16 microg/ml), while the other, of serogroup 14, was
      intermediate in its resistance to penicillin (MIC = 0.25 microg/ml). To our
      knowledge, these are the first two strains to be isolated in Spain with such high
      levels of resistance to cefotaxime.

PMID- 9756797
TI  - Clustering of anophthalmia and microphthalmia. No clustering has been found-but a
      link seems to exist with population density.

PMID- 9756798
TI  - Ageing costs. Evidence to royal commission emphasises need for explicit standards
      and funding.

PMID- 9756799
TI  - Paediatric transplantation comes of age. The main problem now is shortage of
      donors.

PMID- 9756800
TI  - The European Medicines Evaluation Agency: open to criticism. Transparency must be
      coupled with greater rigour.

PMID- 9756801
TI  - Is the FDA approving drugs too fast?. Probably not--but drug recalls have sparked
      debate.

PMID- 9756802
TI  - The NHS's new information strategy. Emphasises putting information to work for
      patients and staff, not technology.

PMID- 9756803
TI  - Geographical variation in anophthalmia and microphthalmia in England, 1988-94.
AB  - OBJECTIVE: To investigate the geographical variation and clustering of congenital
      anophthalmia and microphthalmia in England, in response to media reports of
      clusters. DESIGN: Comparison of pattern of residence at birth of cases of
      anophthalmia and microphthalmia in England in 1988-94, notified to a special
      register, with pattern of residence of all births. Three groups studied included
      all cases, all severe cases, and all severe cases of unknown aetiology. OUTCOME
      MEASURES: Prevalence rates of anophthalmia and microphthalmia by region and
      district, and by ward population density and socioeconomic deprivation index of
      enumeration district grouped into fifths. Clustering expressed as the tendency
      for the three nearest neighbours of a case to be more likely to be cases than
      expected by chance, or for there to be more cases within circles of fixed radius
      of a case than expected by chance. RESULTS: The overall prevalence of
      anophthalmia and microphthalmia was 1.0 per 10 000 births. Regional and district
      variation in prevalence did not reach statistical significance. Prevalence was
      higher in rural than urban areas: the relative risk in the group of wards of
      lowest population density compared with the most densely populated group was 1.79
      (95% confidence interval 1.15 to 2.81) for all cases and 2.37 (1.38 to 4. 08) for
      severe cases. There was no evidence of a trend in risk with socioeconomic
      deprivation. There was very little evidence of localised clustering. CONCLUSIONS:
      There is very little evidence to support the presence of strongly localised
      environmental exposures causing clusters of children to be born with anophthalmia
      or microphthalmia. The excess risk in rural areas requires further investigation.

PMID- 9756805
TI  - Diagnostic trends 

PMID- 9756804
TI  - The hazards of self management 

PMID- 9756806
TI  - Serendipidity 

PMID- 9756808
TI  - Extracorporeal membrane oxygenation 

PMID- 9756807
TI  - Economic evaluation and randomised controlled trial of extracorporeal membrane
      oxygenation: UK collaborative trial. The Extracorporeal Membrane Oxygenation
      Economics Working Group.
AB  - OBJECTIVE: To compare the resource implications and short term outcomes of
      extracorporeal membrane oxygenation and conventional management for term babies
      with severe respiratory failure. DESIGN: Cost effectiveness evaluation alongside
      a randomised controlled trial. SETTING: 55 approved recruiting hospitals in the
      United Kingdom. These hospitals provided conventional management, but infants
      randomised to extracorporeal membrane oxygenation were transferred to one of five
      specialist centres. SUBJECTS: 185 mature newborn infants (gestational age at
      birth >35 weeks, birth weight >2 kg) with severe respiratory failure (oxygenation
      index >40) recruited between 1993 and 1995. The commonest diagnoses were
      persistent pulmonary hypertension due to meconium aspiration, congenital
      diaphragmatic hernia, isolated persistent fetal circulation, sepsis, and
      idiopathic respiratory distress syndrome. MAIN OUTCOME MEASURE: Cost
      effectiveness based on survival at 1 year of age without severe disability.
      RESULTS: 63 (68%) of the 93 infants randomised to extracorporeal membrane
      oxygenation survived to 1 year compared with 38 (41%) of the 92 infants who
      received conventional management. Of those that survived, one infant in each arm
      was lost to follow up and the proportion with disability at 1 year was similar in
      the two arms of the trial. One child in each arm had severe disability. The
      estimated additional cost of extracorporeal membrane oxygenation per additional
      surviving infant without severe disability was 51 222 pounds and the cost per
      surviving infant with no disability was 75 327 pounds. CONCLUSIONS:
      Extracorporeal membrane oxygenation for term neonates with severe respiratory
      failure would increase overall survival without disability. Although the policy
      will increase costs of neonatal health care, it is likely to be as cost effective
      as other life extending technologies.

PMID- 9756809
TI  - Income distribution, socioeconomic status, and self rated health in the United
      States: multilevel analysis.
AB  - OBJECTIVE: To determine the effect of inequalities in income within a state on
      self rated health status while controlling for individual characteristics such as
      socioeconomic status. DESIGN: Cross sectional multilevel study. Data were
      collected on income distribution in each of the 50 states in the United States.
      The Gini coefficient was used to measure statewide inequalities in income. Random
      probability samples of individuals in each state were collected by the 1993 and
      1994 behavioural risk factor surveillance system, a random digit telephone
      survey. The survey collects information on an individual's income, education,
      self rated health and other health risk factors. SETTING: All 50 states.
      SUBJECTS: Civilian, non-institutionalised (that is, non-incarcerated and non
      hospitalised) US residents aged 18 years or older. MAIN OUTCOME MEASURE: Self
      rated health status. RESULTS: When personal characteristics and household income
      were controlled for, individuals living in states with the greatest inequalities
      in income were 30% more likely to report their health as fair or poor than
      individuals living in states with the smallest inequalities in income.
      CONCLUSIONS: Inequality in the distribution of income was associated with an
      adverse impact on health independent of the effect of household income.

PMID- 9756810
TI  - Trends in prenatal screening for and diagnosis of Down's syndrome: England and
      Wales, 1989-97.

PMID- 9756811
TI  - Effect of parity, gravidity, previous miscarriage, and age on risk of Down's
      syndrome: population based study.

PMID- 9756812
TI  - Bullying in schools: self reported anxiety, depression, and self esteem in
      secondary school children.

PMID- 9756814
TI  - An effective reproof 

PMID- 9756813
TI  - Postmarketing surveillance study of a non-chlorofluorocarbon inhaler according to
      the safety assessment of marketed medicines guidelines.
AB  - OBJECTIVE: To evaluate the safety of a non-chlorofluorocarbon metered dose
      salbutamol inhaler. DESIGN: This was a postmarketing surveillance study,
      conducted under formal guidelines for company sponsored safety assessment of
      marketed medicines (SAMM). A non-randomised, non-interventional, observational
      design compared patients prescribed metered doses of salbutamol delivered by
      inhalers using either hydrofluoroalkane or chlorofluorocarbon as the propellant.
      Follow up was three months. SETTING: 646 general practices throughout the United
      Kingdom. SUBJECTS: 6614 patients with obstructive airways disease (1667 patient
      years of exposure). MAIN OUTCOME MEASURES: Proportions of patients who were:
      admitted to hospital for respiratory diseases, reported adverse side effects, or
      withdrew because of adverse affects. RESULTS: There were no significant
      differences between the hydrofluoroalkane (HFA 134a) and chlorofluorocarbon
      inhaler groups in relation to the proportions of patients admitted to hospital
      for respiratory diseases (odds ratio 0.75; 95% confidence interval 0.51 to 1.08)
      or the proportions who reported adverse events (1.01; 0.88 to 1.17). However,
      more patients using the hydrofluoroalkane inhaler than the chlorofluorocarbon
      inhaler withdrew because of adverse events (3.8% and 0.9% respectively).
      CONCLUSION: The hydrofluoroalkane inhaler was as safe as the chlorofluorocarbon
      inhaler when judged by hospital admissions and adverse affects. The study design
      successfully fulfilled the recommendations of the guidelines. Differences between
      postmarketing surveillance studies and randomised clinical trials in assessing
      safety were identified. These may lead to difficulties in the design of
      postmarketing surveillance studies.

PMID- 9756816
TI  - Car health 

PMID- 9756815
TI  - Xenotransplantation.

PMID- 9756818
TI  - Harvard's swimming test 

PMID- 9756817
TI  - Provision of oxygen at home.

PMID- 9756819
TI  - Certifying fitness for corporal punishment.

PMID- 9756820
TI  - Long stay care and the NHS: discontinuities between policy and practice.

PMID- 9756821
TI  - The new NHS: A medical reply to the minister 

PMID- 9756822
TI  - Sending the right message 

PMID- 9756823
TI  - New drug treatment for Alzheimer's disease. Doctors want to offer more than
      sympathy.

PMID- 9756824
TI  - Age is not only criterion for flu vaccine.

PMID- 9756825
TI  - Discrepancy remains in pharmaceutical prescriptions in four European countries.

PMID- 9756827
TI  - WHO haemoglobin colour scale is modern version of what was used previously.

PMID- 9756826
TI  - Informed consent. Numbers inform the debate.

PMID- 9756828
TI  - Protecting breast feeding from breast milk substitutes. Royal college supports
      promotion of breast feeding.

PMID- 9756829
TI  - Doctors and patients should sign prescriptions.

PMID- 9756830
TI  - Planning the united Kingdom's medical workforce.

PMID- 9756831
TI  - New Labour's new maths is hype.

PMID- 9756832
TI  - Standardisation for age certainly changes proportions of doctors holding merit
      awards.

PMID- 9756833
TI  - David james mearns anderson 

PMID- 9756834
TI  - BMA and health minister will discuss review body remit 

PMID- 9756835
TI  - Going slowly 

PMID- 9756836
TI  - A bump on the head 

PMID- 9756837
TI  - School can be hell 

PMID- 9756838
TI  - The surgeon of crowthorne: A tale of murder, madness and the love of words 

PMID- 9756839
TI  - Chemical sensitivity: the truth about environmental illness 

PMID- 9756841
TI  - No clustering of anophthalmia occurs in england, but prevalence is higher in
      rural areas 

PMID- 9756840
TI  - Caring for ageing populations 

PMID- 9756843
TI  - Health is poorer in US states with larger income inequalities 

PMID- 9756842
TI  - Extracorporeal membrane oxygenation can be cost effective 

PMID- 9756845
TI  - Bullied children are more anxious than their peers 

PMID- 9756844
TI  - Increased parity does not increase the risk of Down's syndrome 

PMID- 9756846
TI  - Inhalers are just as safe without chlorofluorocarbons 

PMID- 9756847
TI  - Solvation, reorganization energy, and biological catalysis.

PMID- 9756848
TI  - The RNA-splicing factor PSF/p54 controls DNA-topoisomerase I activity by a direct
      interaction.
AB  - DNA-topoisomerase I has been implied in RNA splicing because it catalyzes RNA
      strand transfer and activates serine/arginine-rich RNA-splicing factors by
      phosphorylation. Here, we demonstrate a direct interaction between topoisomerase
      I and pyrimidine tract binding protein-associated splicing factor (PSF), a
      cofactor of RNA splicing, which forms heterodimers with its smaller homolog, the
      nuclear RNA-binding protein of 54 kDa (p54). Topoisomerase I, PSF, and p54
      copurified in a 1:1:1 ratio from human A431 cell nuclear extracts. Specific
      binding of topoisomerase I to PSF (but not p54) was demonstrated by
      coimmunoprecipitation and by far Western blotting, in which renatured blots were
      probed with biotinylated topoisomerase I. Chemical cross-linking of pure
      topoisomerase I revealed monomeric, dimeric, and trimeric enzyme forms, whereas
      in the presence of PSF/p54 the enzyme was cross-linked into complexes larger than
      homotrimers. When topoisomerase I was complexed with PSF/p54 it was 16-fold more
      active than the pure enzyme, which could be stimulated 5- and 16-fold by the
      addition of recombinant PSF or native PSF/p54, respectively. A physiological role
      of this stimulatory mechanism seems feasible, because topoisomerase I and PSF
      showed a patched colocalization in A431 cell nuclei, which varied with cell
      cycle.

PMID- 9756849
TI  - The putative tumor suppressors EXT1 and EXT2 are glycosyltransferases required
      for the biosynthesis of heparan sulfate.
AB  - Hereditary multiple exostoses, characterized by multiple cartilaginous tumors, is
      ascribed to mutations at three distinct loci, denoted EXT1-3. Here, we report the
      purification of a protein from bovine serum that harbored the D-glucuronyl (GlcA)
      and N-acetyl-D-glucosaminyl (GlcNAc) transferase activities required for
      biosynthesis of the glycosaminoglycan, heparan sulfate (HS). This protein was
      identified as EXT2. Expression of EXT2 yielded a protein with both
      glycosyltransferase activities. Moreover, EXT1, previously found to rescue
      defective HS biosynthesis (McCormick, C., Leduc, Y., Martindale, D., Mattison,
      K., Esford, L. E., Dyer, A. P., and Tufaro, F. (1998) Nat. Genet. 19, 158-161),
      was shown to elevate the low GlcA and GlcNAc transferase levels of mutant cells.
      Thus at least two members of the EXT family of tumor suppressors encode
      glycosyltransferases involved in the chain elongation step of HS biosynthesis.

PMID- 9756850
TI  - BEGAIN (brain-enriched guanylate kinase-associated protein), a novel neuronal PSD
      95/SAP90-binding protein.
AB  - PSD-95/SAP90 is a synaptic membrane-associated guanylate kinase with three PDZ,
      one SH3, and one guanylate kinase (GK) domain. PSD-95/SAP90 binds various
      proteins through the PDZ domains and organizes synaptic junctions. PSD-95/SAP90
      also interacts with the postsynaptic density (PSD) fraction-enriched protein,
      named SAPAP (also called GKAP and DAP), through the GK domain. SAPAP is Triton X
      100-insoluble and recruits PSD-95/SAP90 into the Triton X-100-insoluble fraction
      in the transfected cells, suggesting that SAPAP may fix PSD-95/SAP90 to the PSD.
      Here we report a novel protein interacting with the GK domain of PSD-95/SAP90,
      BEGAIN. BEGAIN is specifically expressed in brain and enriched in the PSD
      fraction. BEGAIN is Triton X-100-soluble in the transfected cells but is
      recruited to the Triton X-100-insoluble fraction by SAPAP when coexpressed with
      PSD-95/SAP90. BEGAIN may be a novel PSD component associated with the core
      complex of PSD-95/SAP90 and SAPAP.

PMID- 9756851
TI  - The 100-kDa neurotensin receptor is gp95/sortilin, a non-G-protein-coupled
      receptor.
AB  - In this work, the 100-kDa neurotensin (NT) receptor previously purified from
      human brain by affinity chromatography (Zsurger, N., Mazella, J., and Vincent, J.
      P. (1994) Brain Res. 639, 245-252) was cloned from a human brain cDNA library.
      This cDNA encodes a 833-amino acid protein 100% identical to the recently cloned
      gp95/sortilin and was then designated NT3 receptor-gp95/sortilin. The N terminus
      of the purified protein is identical to the sequence of the purified
      gp95/sortilin located immediately after the furin cleavage site. The binding of
      iodinated NT to 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid
      solubilized extracts of COS-7 cells transfected with the cloned cDNA was
      saturable and reversible with an affinity of 10-15 nM. The localization of the
      NT3 receptor-gp95/sortilin into intracellular vesicles was in agreement with
      previous results obtained with the purified receptor and with gp95/sortilin.
      Affinity labeling and binding experiments showed that the 110-kDa NT3 receptor
      can be partly transformed into a higher affinity (Kd = 0.3 nM) 100-kDa protein
      receptor by cotransfection with furin. This 100-kDa NT receptor corresponded to
      the mature form of the receptor. The NT3/gp95/sortilin protein is the first
      transmembrane neuropeptide receptor that does not belong to the superfamily of G
      protein-coupled receptors.

PMID- 9756852
TI  - Activation of Sp1-mediated vascular permeability factor/vascular endothelial
      growth factor transcription requires specific interaction with protein kinase C
      zeta.
AB  - The transcription factor Sp1 is ubiquitously expressed and plays a significant
      role in the constitutive and induced expression of a variety of mammalian genes
      and may even contribute to tumorigenesis. Here, we describe a novel pathway
      whereby Sp1 promotes the transcription of vascular permeability factor/vascular
      endothelial growth factor (VPF/VEGF), a potent angiogenic factor, by interacting
      directly and specifically with protein kinase C zeta (PKC zeta) isoform in renal
      cell carcinoma. PKC zeta binds and phosphorylates the zinc finger region of Sp1.
      Moreover, in the presence of the wild type von Hippel-Lindau gene product, the
      interaction of Sp1 with PKC zeta is inhibited, and in this manner steady state
      levels of Sp1 phosphorylation are decreased significantly. Co-transfection of
      renal cell carcinoma cells and human fibrosarcoma cells with a plasmid
      overexpressing PKC zeta and VPF/VEGF promoter luciferase constructs results in
      activation of Sp1-mediated transcription, whereas expression of a dominant
      negative mutant of PKC zeta repressed this activation. Taken together, our
      results suggest a new pathway of cell signaling through PKC zeta and provide an
      insight into PKC zeta and Sp1-dependent transcriptional regulation of VPF/VEGF
      expression and thus tumor angiogenesis.

PMID- 9756853
TI  - T cell receptor zeta allows stable expression of receptors containing the
      CD3gamma leucine-based receptor-sorting motif.
AB  - The leucine-based motif in the T cell receptor (TCR) subunit CD3gamma constitutes
      a strong internalization signal. In fully assembled TCR this motif is inactive
      unless phosphorylated. In contrast, the motif is constitutively active in
      CD4/CD3gamma and Tac/CD3gamma chimeras independently of phosphorylation and leads
      to rapid internalization and sorting of these chimeras to lysosomal degradation.
      Because the TCRzeta chain rescues incomplete TCR complexes from lysosomal
      degradation and allows stable surface expression of fully assembled TCR, we
      addressed the question whether TCRzeta has the potential to mask the CD3gamma
      leucine-based motif. By studying CD4/CD3gamma and CD16/CD3gamma chimeras, we
      found that CD16/CD3gamma chimeras associated with TCRzeta. The CD16/CD3gamma
      TCRzeta complexes were stably expressed at the cell surface and had a low
      spontaneous internalization rate, indicating that the leucine-based motif in
      these complexes was inactive. In contrast, the CD4/CD3gamma chimeras did not
      associate with TCRzeta, and the leucine-based motif in these chimeras was
      constitutively active resulting in a high spontaneous internalization rate and
      low expression of the chimeras at the cell surface. Thus, our data demonstrate
      that TCRzeta allows stable cell surface expression of receptors containing
      CD3gamma leucine-based motifs by its potential to mask such motifs.

PMID- 9756854
TI  - Steroidogenic acute regulatory protein (StAR) is a sterol transfer protein.
AB  - Steroidogenic acute regulatory protein (StAR) plays a critical role in
      steroidogenesis by enhancing the delivery of substrate cholesterol from the outer
      mitochondrial membrane to the cholesterol side chain cleavage enzyme system on
      the inner membrane. A recombinant StAR protein lacking the first N-terminal 62
      amino acid residues that includes the mitochondrial targeting sequence was shown
      to stimulate the transfer of cholesterol and beta-sitosterol from liposomes to
      heat-treated mitochondria in a dose-, time-, and temperature-dependent manner. A
      recombinant mutant StAR protein that cannot stimulate steroidogenesis by isolated
      mitochondria did not promote sterol transfer. Unlike the more promiscuous lipid
      transfer protein, sterol carrier protein 2 (SCP2), StAR did not stimulate
      phosphatidylcholine transfer in our assay system. The recombinant StAR protein
      increased cholesterol transfer to heat-treated microsomes as well as to heat- and
      trypsin-treated mitochondria. These observations demonstrate that StAR has sterol
      transfer activity, which may reflect an ability to enhance desorption of
      cholesterol from sterol-rich donor membranes. We suggest that the ability of StAR
      to promote sterol transfer explains its steroidogenic activity.

PMID- 9756855
TI  - The non-histone chromatin protein HMG1 protects linker DNA on the side opposite
      to that protected by linker histones.
AB  - Linker histones and HMG1/2 constitute the two major proteins that bind to linker
      DNA in chromatin. While the location of linker histones on the nucleosome has
      attracted considerable research effort, only a few studies have addressed the
      location of HMG1 in the particles. In this study, we use a procedure based on
      micrococcal nuclease digestion of reconstituted nucleosomal particles to which
      HMG1 has been bound, followed by analysis of the protected DNA by restriction
      nuclease digestion, to locate the HMG1 binding site. Nucleosomal particles were
      reconstituted on a 235-base pair DNA fragment, which is known to be a strong
      nucleosome positioning sequence. The results unequivocally show that HMG1
      protects linker DNA on one side of the core particle. Importantly, and possibly
      of physiological relevance, the linker DNA site protected by HMG1 was located on
      the side opposite to that already shown to be protected by linker histone
      binding.

PMID- 9756856
TI  - Binding of alpha-synuclein to brain vesicles is abolished by familial Parkinson's
      disease mutation.
AB  - The presynaptic protein alpha-synuclein has been implicated in the pathogenesis
      of Parkinson's disease. First, two missense mutations A30P and A53T cause
      inheritable early onset Parkinson's disease in some families. Secondly, alpha
      synuclein is present in Lewy bodies of affected nerve cells in the predominant
      sporadic type of Parkinson's disease as well as in dementia with Lewy bodies. We
      demonstrate in the rat optic system that a portion of alpha-synuclein is carried
      by the vesicle-moving fast component of axonal transport and that it binds to rat
      brain vesicles through its amino-terminal repeat region. We find alpha-synuclein
      with the A30P mutation of familial Parkinson's disease devoid of vesicle-binding
      activity and propose that mutant alpha-synuclein may accumulate, leading to
      assembly into Lewy body filaments.

PMID- 9756857
TI  - Glycosylasparaginase-catalyzed synthesis and hydrolysis of beta-aspartyl
      peptides.
AB  - beta-Aspartyl di- and tripeptides are common constituents of mammalian
      metabolism, but their formation and catabolism are not fully understood. In this
      study we provide evidence that glycosylasparaginase (aspartylglucosaminidase), an
      N-terminal nucleophile hydrolase involved in the hydrolysis of the N-glycosidic
      bond in glycoproteins, catalyzes the hydrolysis of beta-aspartyl peptides to form
      L-aspartic acid and amino acids or peptides. The enzyme also effectively
      catalyzes the synthesis of beta-aspartyl peptides by transferring the beta
      aspartyl moiety from other beta-aspartyl peptides or beta-aspartylglycosylamine
      to a variety of amino acids and peptides. Furthermore, the enzyme can use L
      asparagine as the beta-aspartyl donor in the formation of beta-aspartyl peptides.
      The data show that synthesis and degradation of beta-aspartyl peptides are new,
      significant functions of glycosylasparaginase and suggest that the enzyme could
      have an important role in the metabolism of beta-aspartyl peptides.

PMID- 9756858
TI  - Production of human compatible high mannose-type (Man5GlcNAc2) sugar chains in
      Saccharomyces cerevisiae.
AB  - A yeast mutant capable of producing Man5GlcNAc2 human compatible sugar chains on
      glycoproteins was constructed. An expression vector for alpha-1,2-mannosidase
      with the "HDEL" endoplasmic reticulum retention/retrieval tag was designed and
      expressed in Saccharomyces cerevisiae. An in vitro alpha-1,2-mannosidase assay
      and Western blot analysis showed that it was successfully localized in the
      endoplasmic reticulum. A triple mutant yeast lacking three glycosyltransferase
      activities was then transformed with an alpha-1, 2-mannosidase expression vector.
      The oligosaccharide structures of carboxypeptidase Y as well as cell surface
      glycoproteins were analyzed, and the recombinant yeast was shown to produce a
      series of high mannose-type sugar chains including Man5GlcNAc2. This is the first
      report of a recombinant S. cerevisiae able to produce Man5GlcNAc2
      oligosaccharides, the intermediate for hybrid-type and complex-type sugar chains.

PMID- 9756859
TI  - Hydrolysis of ATP at only one GyrB subunit is sufficient to promote supercoiling
      by DNA gyrase.
AB  - Mutation of Glu42 to Ala in the B subunit of DNA gyrase abolishes ATP hydrolysis
      but not nucleotide binding. Gyrase complexes that contain one wild-type and one
      Ala42 mutant B protein were formed, and the ability of such complexes to
      hydrolyze ATP was investigated. We found that ATP hydrolysis was able to proceed
      independently only in the wild-type subunit, albeit at a lower rate. With only
      one ATP molecule hydrolyzed at a time, gyrase could still perform supercoiling,
      but the limit of this reaction was lower than that observed when both subunits
      can hydrolyze the nucleotide.

PMID- 9756860
TI  - Involvement of waaY, waaQ, and waaP in the modification of Escherichia coli
      lipopolysaccharide and their role in the formation of a stable outer membrane.
AB  - The waaY, waaQ, and waaP genes are located in the central operon of the waa
      (formerly rfa) locus on the chromosome of Escherichia coli. This locus contains
      genes whose products are involved in the assembly of the core region of the
      lipopolysaccharide molecule. In the R1 core prototype strain, E. coli F470, there
      are nine genes in this operon, and all but waaY, waaQ, and waaP have been
      assigned function. In this study, the waaY, waaQ, and waaP genes were
      independently mutated by insertion of a non-polar antibiotic resistance cassette,
      and the structures of the resulting mutant core oligosaccharides were determined
      by chemical analyses and phosphorus-nuclear magnetic resonance spectroscopy. All
      three of these mutations were shown to affect the modification of the heptose
      region of the core, a region whose structure is critical to outer membrane
      stability. Mutation of waaY resulted in a core oligosaccharide devoid of
      phosphate on HepII. Mutation of waaQ resulted in loss of the branch HepIII
      residue on HepII and impeded the activity of WaaY. Mutation of waaP resulted in
      loss of phosphoryl substituents on HepI and obviated WaaQ and WaaY activity. Only
      mutation of waaP resulted in hypersensitivity to novobiocin and sodium dodecyl
      sulfate, a characteristic of deep-rough mutations.

PMID- 9756861
TI  - Trypanosoma brucei gamma-glutamylcysteine synthetase. Characterization of the
      kinetic mechanism and the role of Cys-319 in cystamine inactivation.
AB  - The parasitic protozoan Trypanosoma brucei utilizes a conjugate of glutathione
      and spermidine, termed trypanothione, in place of glutathione to maintain
      cellular redox balance. The first committed step in the biosynthesis of
      glutathione and thereby trypanothione, is catalyzed by gamma-glutamylcysteine
      synthetase (gamma-GCS). We have determined the kinetic mechanism for T. brucei
      gamma-GCS. The kinetics are best described by a rapid equilibrium random ter
      reactant mechanism, in which the model derived Kd values for the binding of L
      Glu, L-alpha-aminobutyrate, and ATP to free enzyme are 2.6, 5.1, and 1.4 mM,
      respectively. However, significant dependences exist between the binding of some
      of the substrate pairs. The binding of either ATP or L-Glu to the enzyme
      increases the binding affinity of the other by 18-fold, whereas the binding of L
      Glu or L-alpha-aminobutyrate decreases the binding affinity of the other by 6
      fold. Similarly to the mammalian enzyme, cystamine is a time-dependent,
      irreversible inhibitor of T. brucei gamma-GCS. It has been suggested by several
      studies that cystamine labels an active site Cys residue essential for catalysis.
      Among the enzymes reported to be inactivated by cystamine, only one Cys residue
      is invariant (Cys-319 in T. brucei gamma-GCS). Mutation of Cys-319 to Ala in T.
      brucei gamma-GCS renders the enzyme insensitive to cystamine inactivation without
      significantly affecting the enzyme's catalytic efficiency, kinetic mechanism, or
      substrate affinities. These studies suggest that cystamine inactivates the enzyme
      by blocking substrate access to the active site and not by labeling an essential
      active site residue.

PMID- 9756862
TI  - Rapid mechanotransduction in situ at the luminal cell surface of vascular
      endothelium and its caveolae.
AB  - The vascular endothelium is uniquely positioned between the blood and tissue
      compartments to receive directly the fluid forces generated by the blood flowing
      through the vasculature. These forces invoke specific responses within
      endothelial cells and serve to modulate their intrinsic structure and function.
      The mechanisms by which hemodynamic forces are detected and converted by
      endothelia into a sequence of biological and even pathological responses are
      presently unknown. By purifying and subfractionating the luminal endothelial cell
      plasma membrane from tissue, we show, for the first time, that not only does
      mechanotransduction occur at the endothelial cell surface directly exposed to
      vascular flow in vivo but also increased flow in situ induces rapid tyrosine
      phosphorylation of luminal endothelial cell surface proteins located primarily in
      the plasmalemmal invaginations called caveolae. Increased flow induces the
      translocation of signaling molecules primarily to caveolae, ultimately activating
      the Ras-Raf-mitogen-activated protein kinase pathway. This signaling appears to
      require intact caveolae. Filipin-induced disassembly of caveolae inhibits both
      proximal signaling events at the cell surface and downstream activation of the
      mitogen-activated protein kinase pathway. With the molecular machinery required
      for mediating rapid flow-induced responses as seen in endothelium, caveolae may
      be flow-sensing organelles converting mechanical stimuli into chemical signals
      transmitted into the cell.

PMID- 9756863
TI  - An all-ferrous state of the Fe protein of nitrogenase. Interaction with
      nucleotides and electron transfer to the MoFe protein.
AB  - The MoFe protein of nitrogenase catalyzes the six-electron reduction of
      dinitrogen to ammonia. It has long been believed that this protein receives the
      multiple electrons it requires one at a time, from the [4Fe-4S]2+/+ couple of the
      Fe protein. Recently an all-ferrous [4Fe-4S]0 state of the Fe protein was
      demonstrated suggesting instead a series of two electron steps involving the [4Fe
      4S]2+/0 couple. We have examined the interactions of the [4Fe-4S]0 Fe protein
      with nucleotides and its ability to transfer electrons to the MoFe protein. The
      [4Fe-4S]0 Fe protein binds both MgATP and MgADP and undergoes the MgATP induced
      conformational change and then binds properly to the MoFe protein, as evidenced
      by the fact that the behavior of the 0 and +1 oxidation states in the chelation
      and chelation protection assays are indistinguishable. Nucleotide binding does
      not effect the distinctive UV/Vis, CD, or Mossbauer spectra exhibited by the [4Fe
      4S]0 Fe protein; however, because the intensity of the g = 16.4 EPR signal of the
      [4Fe-4S]0 Fe protein is extremely sensitive to minor variations of the rhombicity
      parameter E/D, the EPR signal is sensitive to the binding of nucleotides. A 50:50
      mixture of [4Fe-4S]2+ and [4Fe-4S]0 Fe protein results in electron self-exchange
      and 100% production of [4Fe-4S]+ Fe protein, demonstrating that the +1/0 couple
      is fully reversible. MgATP is absolutely required for electron transfer from the
      [4Fe-4S]0 Fe protein to the reduced state of the MoFe protein. In that reaction
      both electrons are transferred and are used to reduce substrate.

PMID- 9756864
TI  - The efficient cellular uptake of high density lipoprotein lipids via scavenger
      receptor class B type I requires not only receptor-mediated surface binding but
      also receptor-specific lipid transfer mediated by its extracellular domain.
AB  - The class B type I scavenger receptor, (SR-BI), is a member of the CD36
      superfamily of proteins and is a physiologically relevant, high affinity cell
      surface high density lipoprotein (HDL) receptor that mediates selective lipid
      uptake. The mechanism of selective lipid uptake is fundamentally different from
      that of classic receptor-mediated uptake via coated pits and vesicles (e.g. the
      low density lipoprotein receptor pathway) in that it involves efficient transfer
      of the lipids, but not the outer shell proteins, from HDL to cells. The abilities
      of SR-BI and CD36, both of which are class B scavenger receptors, to bind HDL and
      mediate cellular uptake of HDL-associated lipid when transiently expressed in COS
      cells were examined. For these experiments, the binding of HDL to cells was
      assessed using either 125I- or Alexa (a fluorescent dye)-HDL in which the
      apolipoproteins on the surface of the HDL particles were covalently modified.
      Lipid transfer was measured using HDL noncovalently labeled by the fluorescent
      lipid 1,1'-dioctadecyl-3,3, 3',3'-tetramethylindocarbocyanine perchlorate.
      Although both mSR-BI and human CD36 (hCD36) could mediate the binding of HDL in a
      punctate pattern across the surfaces of cells, only mSR-BI efficiently mediated
      the transfer of lipid to the cells. Analysis of point mutants established that
      the major sites of fatty acylation of mSR-BI are Cys462 and Cys470 and that fatty
      acylation is not required for receptor clustering, HDL binding, or efficient
      lipid transfer. Generation of mSR-BI/hCD36 domain swap chimeras showed that the
      differences in lipid uptake activities between mSR-BI and hCD36 were not due to
      differences between their two sets of transmembrane and cytoplasmic domains but
      rather result from differences in their large extracellular loop domains. These
      results show that high affinity binding to a cell surface receptor is not
      sufficient to ensure efficient cellular lipid uptake from HDL. Thus, SR-BI
      mediated binding combined with SR-BI-dependent facilitated transfer of lipid from
      the HDL particle to the cell appears to be the most likely mechanism for the bulk
      of the selective uptake of cholesteryl esters from HDL to the liver and
      steroidogenic tissues.

PMID- 9756865
TI  - Structural analysis of the fds operon encoding the NAD+-linked formate
      dehydrogenase of Ralstonia eutropha.
AB  - The fdsGBACD operon encoding the four subunits of the NAD+-reducing formate
      dehydrogenase of Ralstonia eutropha H16 was cloned and sequenced. Sequence
      comparisons indicated a high resemblance of FdsA (alpha-subunit) to the catalytic
      subunits of formate dehydrogenases containing a molybdenum (or tungsten)
      cofactor. The NH2-terminal region (residues 1-240) of FdsA, lacking in formate
      dehydrogenases not linked to NAD(P)+, exhibited considerable similarity to that
      of NuoG of the NADH:ubiquinone oxidoreductase from Escherichia coli as well as to
      HoxU and the NH2-terminal segment of HndD of NAD(P)+-reducing hydrogenases. FdsB
      (beta-subunit) and FdsG (gamma-subunit) are closely related to NuoF and NuoE,
      respectively, as well as to HoxF and HndA. It is proposed that the NH2-terminal
      domain of FdsA together with FdsB and FdsG constitute a functional entity
      corresponding to the NADH dehydrogenase (diaphorase) part of NADH:ubiquinone
      oxidoreductase and the hydrogenases. No significant similarity to any known
      protein was observed for FdsD (delta-subunit). The predicted product of fdsC
      showed the highest resemblance to FdhD from E. coli, a protein required for the
      formation of active formate dehydrogenases in this organism. Transcription of the
      fds operon is subject to formate induction. A promoter structure resembling the
      consensus sequence of sigma70-dependent promoters from E. coli was identified
      upstream of the transcriptional start site determined by primer extension
      analysis.

PMID- 9756866
TI  - Intracellular retention of recombinant GABAB receptors.
AB  - gamma-Aminobutyric acid type B (GABAB) receptors mediate the transmission of slow
      and prolonged inhibitory signals in the central nervous system. Two splice
      variants of GABAB receptors, GABABR1a and GABABR1b, were recently cloned from a
      mouse cortical and cerebellar cDNA library. As predicted, these receptors belong
      to the G protein-coupled receptor superfamily. We have used epitope-tagged
      versions of GABABR1a receptors to study the cellular distribution of these
      proteins in a variety of non-neuronal and neuronal cell types. Here we report
      that recombinant GABAB receptors fail to reach the cell surface when expressed in
      heterologous systems and are retained in the endoplasmic reticulum when
      introduced into COS cells. In addition, we prove that recombinant GABAB receptors
      are excluded from the cell surface when overexpressed in ganglion neurons and we
      further demonstrate that they fail to activate in superior cervical ganglion
      neurons. Together our observations suggest that recombinant GABAB receptors
      require additional information for functional targeting to the plasma membrane.

PMID- 9756867
TI  - Molecular basis for substrate specificity of protein-tyrosine phosphatase 1B.
AB  - Protein-tyrosine phosphatases can exhibit stringent substrate specificity in
      vivo, although the molecular basis for this is not well understood. The three
      dimensional structure of the catalytically inactive protein-tyrosine phosphate 1B
      (PTP1B)/C215S complexed with an optimal substrate, DADEpYL-NH2, reveals specific
      interactions between amino acid residues in the substrate and PTP1B. The goal of
      this work is to rigorously evaluate the functional significance of Tyr46, Arg47,
      Asp48, Phe182, and Gln262 in substrate binding and catalysis, using site-directed
      mutagenesis. Combined with structural information, kinetic analysis of the wild
      type and mutant PTP1B using p-nitrophenyl phosphate and phosphotyrosine
      containing peptides has yielded further insight into PTP1B residues, which
      recognize general features, as well as specific properties, in peptide
      substrates. In addition, the kinetic results suggest roles of these residues in E
      P hydrolysis, which are not obvious from the structure of PTP1B/peptide complex.
      Thus, Tyr46 and Asp48 recognize common features of peptide substrates and are
      important for peptide substrate binding and/or E-P formation. Arg47 acts as a
      determinant of substrate specificity and is responsible for the modest preference
      of PTP1B for acidic residues NH2-terminal to phosphotyrosine. Phe182 and the
      invariant Gln262 are not only important for substrate binding and/or E-P
      formation but also important for the E-P hydrolysis step.

PMID- 9756868
TI  - Importance of phenylalanine residues of yeast calmodulin for target binding and
      activation.
AB  - Recent genetic studies of yeast calmodulin (yCaM) have shown that alterations of
      different sets of Phe residues result in distinct functional defects (Ohya, Y.,
      and Botstein, D. (1994) Science 263, 963-966). To examine the importance of Phe
      residues for target binding and activation, we purified mutant yCaMs containing
      single or double Phe to Ala substitutions and determined their ability to bind
      and activate two target proteins, calcineurin and CaM-dependent protein kinase
      (CaMK). Binding assays using the gel overlay technique and quantitative analyses
      using surface plasmon resonance measurements indicated that the binding of yCaM
      to calcineurin is impaired by either double mutations of F16A/F19A or a single
      mutation of F140A, while binding to CaMK is impaired by F89A, F92A, or F140A.
      These same mutant yCaMs fail to activate calcineurin and CaMK, respectively, in
      vitro. In addition, F19A exhibited a severe defect in activation of both enzymes.
      F12A activated calcineurin to only 50% of the level achieved by wild-type
      calmodulin but fully activated CaMK. These results suggest that each target
      protein requires a specific and distinct subset of Phe residues in yCaM for
      target binding and activation.

PMID- 9756869
TI  - Mechanism of cloned ATP-sensitive potassium channel activation by oleoyl-CoA.
AB  - Insulin secretion from pancreatic beta cells is coupled to cell metabolism
      through closure of ATP-sensitive potassium (KATP) channels, which comprise Kir6.2
      and sulfonylurea receptor (SUR1) subunits. Although metabolic regulation of KATP
      channel activity is believed to be mediated principally by the adenine
      nucleotides, other metabolic intermediates, including long chain acyl-CoA esters,
      may also be involved. We recorded macroscopic and single-channel currents from
      Xenopus oocytes expressing either Kir6.2/SUR1 or Kir6. 2DeltaC36 (which forms
      channels in the absence of SUR1). Oleoyl-CoA (1 microM) activated both wild-type
      Kir6.2/SUR1 and Kir6.2DeltaC36 macroscopic currents, approximately 2-fold, by
      increasing the number and open probability of Kir6.2/SUR1 and Kir6.2DeltaC36
      channels. It was ineffective on the related Kir subunit Kir1.1a. Oleoyl-CoA also
      impaired channel inhibition by ATP, increasing the Ki values for both Kir6.2/SUR1
      and Kir6.2DeltaC36 currents by approximately 3-fold. Our results indicate that
      activation of KATP channels by oleoyl-CoA results from an interaction with the
      Kir6.2 subunit, unlike the stimulatory effects of MgADP and diazoxide which are
      mediated through SUR1. The increased activity and reduced ATP sensitivity of KATP
      channels by oleoyl-CoA might contribute to the impaired insulin secretion
      observed in non-insulin-dependent diabetes mellitus.

PMID- 9756870
TI  - Overexpression and accumulation of apolipoprotein E as a cause of
      hypertriglyceridemia.
AB  - The molecular mechanisms of hypertriglyceridemia (HTG), a common lipid metabolic
      disorder in humans, often of genetic origin, are not well understood. In studying
      the effect of apolipoprotein (apo) E on the metabolism of triglyceride-rich
      lipoproteins, we found that expressing high plasma levels of human apoE3 in
      transgenic mice lacking endogenous mouse apoE caused HTG. These transgenic
      animals had 3-fold higher plasma triglyceride levels, higher very low density
      lipoproteins (VLDL), and lower high density lipoproteins than did nontransgenics.
      Removing one or both low density lipoprotein receptor alleles in the apoE3
      overexpressing mice caused severe HTG (8-11-fold over nontransgenics) and
      increased VLDL and decreased low and high density lipoproteins, and apoE3
      enriched VLDL were markedly depleted in apoC-II. At least two mechanisms could
      explain HTG associated with apoE3 overexpression: stimulated VLDL triglyceride
      production and impaired VLDL lipolysis. The apoE3 mice with HTG had a 50%
      increase in hepatic VLDL triglyceride production. Furthermore, overexpression of
      apoE (E2, E3, or E4) in cultured hepatocytes (McA-RH7777 cells) correlated
      positively with secretion of VLDL into the medium. However, apoE3 overexpression
      associated HTG was only partially explained by VLDL overproduction, as
      lipoprotein lipase-mediated VLDL lipolysis was also decreased 20-86% depending on
      apoE3 levels, most likely by displacing or masking apoC-II on the particles. In
      human subjects, HTG correlated positively with increased VLDL triglyceride and
      plasma and VLDL apoE levels. However, plasma and VLDL apoE correlated negatively
      with VLDL apoC-II levels and lipoprotein lipase-mediated VLDL lipolysis. Thus,
      optimal expression of apoE is crucial for normal metabolism of triglyceride-rich
      lipoproteins, and overexpression and/or accumulation of apoE may contribute to
      HTG by stimulating VLDL triglyceride production and by impairing VLDL lipolysis.
      The apoE3-overexpressing mice will be useful for studying the pathophysiology of
      this disorder.

PMID- 9756871
TI  - Potential of Escherichia coli GTP cyclohydrolase II for hydrolyzing 8-oxo-dGTP, a
      mutagenic substrate for DNA synthesis.
AB  - MutT protein of Escherichia coli prevents the occurrence of A:T --> C:G
      transversion by hydrolyzing an oxidized form of dGTP, 8-oxo-7, 8-dihydro-2'
      deoxyguanosine 5'-triphosphate (8-oxo-dGTP), which is produced by active oxygen
      species. In a search for mutT-related genes, we found that the ribA gene,
      encoding GTP cyclohydrolase II, is able to reduce the increased level of mutation
      frequency of the mutT strain to almost the normal level, provided that the gene
      product is overproduced. Purified preparations of Escherichia coli GTP
      cyclohydrolase II protein as well as the histidine hexamer-tagged recombinant GTP
      cyclohydrolase II protein efficiently hydrolyze 8-oxo-dGTP and 8-oxo-GTP,
      producing 8-oxo-dGMP and 8-oxo-GMP, respectively. dGTP was not hydrolyzed by
      these preparations. GTP cyclohydrolase II catalyzes conversion of GTP to 2, 5
      diamino-6-hydroxy-4-(5-phosphoribosylamino)-pyrimidine, which constitutes the
      first step for riboflavin synthesis. The Km values for the three types of guanine
      nucleotides, GTP, 8-oxo-GTP, and 8-oxo-dGTP, were almost the same. In the mutT-
      background, ribA- cells showed higher spontaneous mutation frequencies as
      compared with that of ribA+ cells. Thus, GTP cyclohydrolase II, the ribA gene
      product, has a potential to protect genetic material from the untoward effects of
      endogenous oxygen radicals.

PMID- 9756872
TI  - Topology of the Na+/proline transporter of Escherichia coli.
AB  - Hydropathy profile analysis of the amino acid sequence of the Na+/proline
      transporter of Escherichia coli (PutP) suggests that the protein consists of 12
      transmembrane domains (TMs) which are connected by hydrophilic loops (Nakao, T.,
      Yamato, I., and Anraku, Y. (1987) Mol. Gen. Genet. 208, 70-75). We have tested
      this prediction by applying a gene fusion approach in combination with a Cys
      accessibility analysis and site-specific proteolysis. Characterization of a
      series of PutP-alkaline phosphatase (PhoA) and PutP-beta-galactosidase (LacZ)
      hybrid proteins yields a reciprocal activity pattern of the reporter proteins
      that is in agreement with the topology of TMs III to XII of the 12-helix model.
      Placement of the PutP-PhoA and PutP-LacZ junction sites closer to the N terminus
      does not yield conclusive results. As a prerequisite for further topology
      studies, a functional PutP molecule devoid of all five native Cys residues (Cys
      free PutP) is generated. Subsequently, amino acids in Cys-free PutP are replaced
      individually with Cys, and the accessibility of the sulfhydryl groups is
      analyzed. Surprisingly, Cys residues placed close to the N terminus of PutP (Ile
      3 --> Cys, Thr-5 --> Cys) or into putative TM II (Ser-71 --> Cys, Glu-75 --> Cys)
      are highly accessible to membrane permeant and impermeant thiol reagents in
      intact cells. In contrast, Cys at the C terminus (Ser-502 --> Cys) reacts only
      with the membrane permeant but not with the impermeant reagent in intact cells.
      These results contradict the 12-helix motif and indicate a periplasmic location
      of the N terminus whereas the C terminus faces the cytoplasm. In addition, a
      transporter with Cys in place of Leu-37 (putative periplasmic loop (pL2) shows
      the same accessibility pattern as the Cys at the C terminus. Furthermore, PutP
      which has been purified and reconstituted into proteoliposomes in an inside-out
      orientation, is readily cleaved by the endoproteinase AspN before Asp-33 (pL2),
      Asp-112 (putative cytoplasmic loop (cL3), Asp-262 (cL7), and Asp-356 (cL9). These
      results suggest a cytosolic location of Asp-33 and Leu-37, thereby implying the
      formation of an additional TM formed by amino acids of pL2. Based on these
      observations, a new secondary structure model is proposed according to which the
      protein consists of 13 TMs with the N terminus on the outside and the C terminus
      facing the cytoplasm. The 13-helix structure is discussed as a common topological
      motif for all members of the Na+/solute cotransporter family.

PMID- 9756873
TI  - Human aggrecan keratan sulfate undergoes structural changes during adolescent
      development.
AB  - Alkaline borohydride-reduced keratan sulfate chains were isolated from human
      articular cartilage aggrecan from individuals of various ages (0-85 years old).
      The chains were structurally characterized using 1H NMR spectroscopy, gel
      permeation chromatography, and oligosaccharide profiling (after digestion with
      the enzymes keratanase and keratanase II). The results show that from birth to
      early adolescence (0-9 years) the levels of alpha(1-3)-fucosylation, alpha(2-3)
      sialylation, and galactose sulfation increase. Also, the weight-average molecular
      weight of the chains increases. During maturation (9-18 years) the levels of
      fucosylation and galactose sulfation continue to increase and alpha(2-6)
      sialylation of the chains occurs. In adult life (18-85 years) there is little
      change in the weight-average molecular weight of the chains, and the levels of
      fucosylation, sialylation, and sulfation remain fairly constant.

PMID- 9756874
TI  - Individual substitutions of clustered arginine residues of the sensor kinase KdpD
      of Escherichia coli modulate the ratio of kinase to phosphatase activity.
AB  - Escherichia coli responds to K+ limitation or high osmolarity by induction of the
      kdpFABC operon coding for the high affinity K+-translocating Kdp-ATPase. KdpD,
      the sensor kinase of this system, is a bifunctional enzyme catalyzing the
      autophosphorylation by ATP and the dephosphorylation of the corresponding
      response regulator KdpE. Here we demonstrate that individual replacements of
      clustered arginine residues located close to transmembrane domain TM4 modulate
      the ratio of kinase to phosphatase activity. Thus KdpD-Arg511 --> Gln is
      characterized by an increase in the kinase activity and a loss of the phosphatase
      activity. However, when Arg at position 511 is replaced with Lys, activities of
      the corresponding protein are comparable with wild-type KdpD. In contrast,
      replacement of arginine residues at positions 503, 506, or 508 with glutamine or
      lysine causes a decrease of the kinase and an increase of the phosphatase
      activities. Changes of the activities of these KdpD proteins correspond with
      alterations in kdpFABC expression. Thus KdpD-Arg511 --> Gln causes constitutive
      expression of kdpFABC. KdpD proteins with Arg replacements at positions 503, 506,
      or 508 are unable to respond to osmolarity, whereas the sensing of K+ limitation
      is not influenced. Simultaneous replacement of arginine residues 508 and 511 or
      506, 508, and 511 with glutamine leads to a decrease of the phosphatase activity.
      However, kdpFABC expression is dependent on K+ and osmolarity. Finally, when
      Arg513 is replaced with glutamine the amount of KdpD detected in the membrane is
      drastically reduced. These results imply that there is an equilibrium between the
      kinase and phosphatase activities of KdpD, which can be shifted by the
      replacement of one arginine residue. An electrostatic switch mechanism within the
      protein is proposed through which the ratio of kinase to phosphatase is
      regulated. Finally, these results lend support to the notion that KdpD can be
      activated by two distinct stimuli, K+ limitation and osmolarity.

PMID- 9756875
TI  - Overexpression of protein targeting to glycogen (PTG) in rat hepatocytes causes
      profound activation of glycogen synthesis independent of normal hormone- and
      substrate-mediated regulatory mechanisms.
AB  - Protein targeting to glycogen (PTG), also known as PPP1R5, is a widely expressed
      member of a growing family of proteins that target protein phosphatase-1 (PP-1)
      to glycogen particles. Because PTG also binds to glycogen synthase and
      phosphorylase kinase, it has been suggested that it serves as a "scaffold" for
      efficient activation of glycogen synthesis. However, very little is known about
      the metabolic effects of PTG. In this study, we have used recombinant adenovirus
      to overexpress PTG in primary rat hepatocytes, a cell type with high glycogenic
      capacity. We find that overexpression of PTG potently activates glycogen
      synthesis in cultured hepatocytes. Surprisingly, the glycogenic effect of PTG is
      observed even in the complete absence of carbohydrates or insulin in the culture
      medium. Furthermore, glycogenolytic agents such as forskolin or glucagon are
      largely ineffective at activating glycogen degradation in PTG overexpressing
      hepatocytes, even though large increases in cAMP levels are demonstrated. These
      metabolic effects of PTG overexpression are accompanied by a 3.6-fold increase in
      glycogen synthase activation state and a 40% decrease in glycogen phosphorylase
      activity. Our results are consistent with a model in which PTG overexpression
      "locks" the hepatocyte in a glycogenic mode, presumably via its ability to
      promote interaction of enzymes of glycogen metabolism with PP-1.

PMID- 9756876
TI  - Genetic probing of the stalk segments associated with M2 and M3 of the plasma
      membrane H+-ATPase from Saccharomyces cerevisiae.
AB  - The stalk region of the H+-ATPase from Saccharomyces cerevisiae has been proposed
      to play a role in coupling ATP hydrolysis to proton transport. Genetic probing
      was used to examine the role of stalk segments S2 and S3, associated with M2 and
      M3, respectively. Saturation mutagenesis was used to explore the role of side
      group character at position Ile183 in S2, at which an alanine substitution was
      shown previously to partially uncouple the enzyme (Wang, G., Tamas, M. J., Hall,
      M. J., Pascual-Ahuir, A., and Perlin, D. S. (1996) J. Biol. Chem. 271, 25438
      25445). Diverse side group substitutions were tolerated at this position,
      although three substitutions, I183N, I183R, and I183Y required second site
      mutations at the C terminus of the enzyme for stabilization. Substitution of
      glycine and proline at Ile183 resulted in lethal phenotypes, suggesting that the
      backbone may be more important than side group at this position. Proline/glycine
      mutagenesis was used to study additional sites in S2 and S3. The substitution of
      proline at Gly186 resulted in a lethal phenotype, whereas substitutions in S3 of
      proline or serine at Gly270 and proline or glycine at Thr287 resulted in viable
      mutants. Mutations G270P and T287P resulted in mutant enzymes that produced
      pronounced growth defects and ATP hydrolysis rates that were 35% and 60% lower
      than wild type enzyme, respectively. The mutant enzymes transported protons at
      rates consistent with their ATPase activity, suggesting that the growth defects
      observed were due to a reduced rate of ATP hydrolysis and not to uncoupling of
      proton transport. The prominent growth phenotypes produced by mutations G270P and
      T287P permitted the isolation of suppressor mutations, which restored wild type
      growth. Most of the suppressors either replaced the primary site mutation with
      alanine or restored the wild type residue by ectopic recombination with PMA2,
      both of which restore alpha-helical tendency. This study suggests that
      maintaining alpha-helical character is essential to S2 and may play an important
      role in S3.

PMID- 9756877
TI  - Cloning and overexpression of glycosyltransferases that generate the
      lipopolysaccharide core of Rhizobium leguminosarum.
AB  - The lipopolysaccharide (LPS) core of the Gram-negative bacterium Rhizobium
      leguminosarum is more amenable to enzymatic study than that of Escherichia coli
      because much of it is synthesized from readily available sugar nucleotides. The
      inner portion of the R. leguminosarum core contains mannose, galactose, and three
      3-deoxy-D-manno-octulosonate (Kdo) residues, arranged in the order: lipid A
      (Kdo)2-Man-Gal-Kdo-[O antigen]. A mannosyltransferase that uses GDP-mannose and
      the conserved precursor Kdo2-[4'-32P]lipid IVA (Kadrmas, J. L., Brozek, K. A.,
      and Raetz, C. R. H. (1996) J. Biol. Chem. 271, 32119-32125) is proposed to
      represent a key early enzyme in R. leguminosarum core assembly. Conditions for
      demonstrating efficient galactosyl- and distal Kdo-transferase activities are now
      described using a coupled assay system that starts with GDP-mannose and Kdo2-[4'
      32P]lipid IVA. As predicted, mannose incorporation precedes galactose addition,
      which in turn precedes distal Kdo transfer. LPS core mutants with Tn5 insertions
      in the genes encoding the putative galactosyltransferase (lpcA) and the distal
      Kdo-transferase (lpcB) are shown to be defective in the corresponding in vitro
      glycosylation of Kdo2-[4'-32P]lipid IVA. We have also discovered the new gene
      (lpcC) that encodes the mannosyltransferase. The gene is separated by several
      kilobase pairs from the lpcAB cluster. All three glycosyltransferases are carried
      on cosmid pIJ1848, which contains at least 20 kilobase pairs of R. leguminosarum
      DNA. Transfer of pIJ1848 into R. meliloti 1021 results in heterologous expression
      of all three enzymes, which are not normally present in strain 1021. Expression
      of the lpc genes individually behind the T7 promoter results in the production of
      each R. leguminosarum glycosyltransferase in E. coli membranes in a catalytically
      active form, demonstrating that lpcA, lpcB, and lpcC are structural genes.

PMID- 9756878
TI  - Autoprocessing and peptide substrates for human herpesvirus 6 proteinase.
AB  - Autoprocessing of the precursor form of human herpesvirus 6 (HHV-6) proteinase at
      two sites (termed M and R) is required to generate the mature enzyme. Kinetic
      constants were determined for the hydrolysis of a series of synthetic peptide
      substrates by mature HHV-6 proteinase, purified to homogeneity. Truncation or
      replacement of individual residues in peptides mimicking the R-site sequence,
      indicated that the minimum length for effective hydrolysis by the viral enzyme
      was P4-P3-P2-Ala*Ser-P2'-P3'-P4' and revealed the importance of the P1 Ala and P4
      Tyr residues. Consequently, relevant (P1 or P4) mutations were introduced into
      the precursor form of the proteinase and the ability of these altered proteins to
      autoprocess was examined. Introduction of Val in place of the P1 Ala at the M
      site essentially abrogated cleavage but mature HHV-6 proteinase was still
      generated by cleavage at the R-site, indicating that processing of the M-site is
      not a prerequisite for cleavage of the R-site in the precursor. At the R-site,
      mutation of the P1 Ala, or of the preceding P4 Tyr residue, prevented processing
      at the R-site in the precursor so that the mature form of HHV-6 proteinase was
      not generated. The accumulated data suggest a possible new approach to the design
      of inhibitors for therapeutic intervention in the life cycle of herpesviruses.

PMID- 9756879
TI  - Electrogenic antiport activities of the Gram-positive Tet proteins include a
      Na+(K+)/K+ mode that mediates net K+ uptake.
AB  - Two Gram-positive Tet proteins, TetA(L) from Bacillus subtilis and TetK from a
      Staphylococcus aureus plasmid, have previously been suggested to have multiple
      catalytic modes and roles. These include: tetracycline (Tc)-metal/H+ antiport for
      both proteins (Yamaguchi, A., Shiina, Y., Fujihira, E., Sawai, T., Noguchi, N.,
      and Sasatsu, M. (1995) FEBS Lett. 365, 193-197; Cheng, J. Guffanti, A. A., Wang,
      W., Krulwich, T. A., and Bechhofer, D. H. (1996) J. Bacteriol. 178, 2853-2860);
      Na+(K+)/H+ antiport for both proteins (Cheng et al. (1996)); and an electrical
      potential-dependent K+ leak mode for TetK and highly truncated segments thereof
      that can facilitate net K+ uptake (Guay, G. G., Tuckman, M., McNicholas, P., and
      Rothstein, D. M. (1993) J. Bacteriol. 175, 4927-4929). Studies of membrane
      vesicles from Escherichia coli expressing low levels of complete and 3'-truncated
      versions of tetA(L) or tetK, now show that the full-length versions of both
      transporters catalyze electrogenic antiport and that demonstration of
      electrogenicity depends upon use of a low chloride buffer for the assay. The K+
      uptake mode, assayed via 86Rb+ uptake, was also catalyzed by both full-length
      TetA(L) and TetK. This mode does not represent a potential-dependent leak. Such a
      leak was not demonstrable in energized membrane vesicles. Rather, Rb+ uptake
      occurred in right-side-out vesicles when the intravesicular space contained
      either Na+ or K+ but not choline. If an outwardly directed gradient of Na+ or K+
      was present, Rb+ uptake occurred without energization in vesicles from cells
      transformed with a plasmid containing tetA(L) or tetK but not a control plasmid.
      Experiments in which a comparable exchange was carried out in low chloride
      buffers to which oxonol was added confirmed that the exchange was electrogenic.
      Thus, the K+ uptake mode is proposed to be a mode of the electrogenic monovalent
      cation/H+ antiport activity of TetA(L) and TetK in which K+ takes the place of
      the external protons. Truncated TetK and TetA(L) failed to catalyze either Tc
      metal/H+ or Na+/H+ antiport in energized everted vesicles. Truncated TetK, but
      not TetA(L), did, however, exhibit modest, electrogenic Na+(K+)/Rb+ exchange as
      well as a small, potential-dependent leak of Rb+. The C-terminal halves of the
      TetA(L) and TetK proteins are thus required both for proton-coupled active
      transport activities of the multifunctional transporter and, perhaps, for
      minimizing cation leakiness.

PMID- 9756880
TI  - Identification and characterization of the RNA chaperone activity of hepatitis
      delta antigen peptides.
AB  - In this study, we identified an activity of the hepatitis delta antigen that both
      modulates the cis-cleaving activities of hepatitis delta virus (HDV) genomic RNA
      fragments and facilitates the trans-cleavage reactions between hammerhead
      ribozymes and the cognate substrates of various lengths in vitro. Hepatitis delta
      antigen peptides exert their effect by accelerating the unfolding and refolding
      of RNA molecules and by promoting strand annealing and strand dissociation. In
      addition, the stimulatory effect of hepatitis delta antigen peptide on hammerhead
      catalysis is observed whether the peptide is removed or not by phenol/chloroform
      extraction prior to the initiation of trans-cleavage reaction. Therefore,
      hepatitis delta antigen peptide acts as an RNA chaperone. The RNA chaperone
      domain of hepatitis delta antigen overlaps with the coiled-coil domain that is
      rich in lysine residues. The RNA binding domains of hepatitis delta antigen
      previously identified are not required for the RNA chaperone activity identified
      herein. The RNA chaperone activity of hepatitis delta antigen may be important
      for the regulation of HDV replication in vivo.

PMID- 9756881
TI  - Electrochemical and spectroscopic properties of the iron-sulfur flavoprotein from
      Methanosarcina thermophila.
AB  - An iron-sulfur flavoprotein (Isf) from the methanoarchaeaon Methanosarcina
      thermophila, which participates in electron transfer reactions required for the
      fermentation of acetate to methane, was characterized by electrochemistry and EPR
      and Mossbauer spectroscopy. The midpoint potential (Em) of the FMN/FMNH2 couple
      was -0.277 V. No flavin semiquinone was observed during potentiometric
      titrations; however, low amounts of the radical were observed when Isf was
      quickly frozen after reaction with CO and the CO dehydrogenase/acetyl-CoA
      synthase complex from M. thermophila. Isf contained a [4Fe-4S]2+/1+ cluster with
      g values of 2.06 and 1.93 and an unusual split signal with g values at 1.86 and
      1.82. The unusual morphology was attributed to microheterogeneity among Isf
      molecules. The Em value for the 2+/1+ redox couple of the cluster was -0.394 V.
      Extracts from H2-CO2-grown Methanobacterium thermoautotrophicum cells catalyzed
      either the H2- or CO-dependent reduction of M. thermophila Isf. In addition, Isf
      homologs were found in the genomic sequences of the CO2-reducing methanoarchaea
      M. thermoautotrophicum and Methanococcus jannaschii. These results support a
      general role for Isf in electron transfer reactions of both acetate-fermenting
      and CO2-reducing methanoarchaea. It is suggested that Isf functions to couple
      electron transfer from ferredoxin to membrane-bound electron carriers, such as
      methanophenazine and/or b-type cytochromes.

PMID- 9756883
TI  - Sequential hydrolysis of ATP molecules bound in interacting catalytic sites of
      Escherichia coli transcription termination protein Rho.
AB  - Escherichia coli transcription termination protein Rho, an RNA-dependent ATPase,
      disrupts transcription complexes, releasing RNA and allowing RNA polymerase to
      recycle. Homohexameric Rho binds three molecules of MgATP in a single class of
      catalytically competent sites. In rapid mix chemical quench experiments, when Rho
      saturated with ATP was mixed with RNA and the reaction was quenched after various
      times, hydrolysis of the three bound ATP molecules was not simultaneous. A
      hydrolysis burst of one molecule of ATP per hexamer occurred at >300 s-1,
      followed by steady-state hydrolysis at 30 s-1 per hexamer. The burst also shows
      that a step following ATP hydrolysis is rate-limiting for overall catalysis and
      requires communication among the three catalytic sites during net ATP hydrolysis.
      The rate of hydrolysis of radiolabeled ATP when one labeled and two unlabeled ATP
      molecules are bound indicates a sequential pattern of hydrolysis. Positive
      cooperativity of catalysis occurs among the catalytic sites of Rho; when only one
      ATP molecule is bound per hexamer, ATP hydrolysis upon addition of RNA is 30-fold
      slower than when ATP is saturating. These behaviors are comparable to those of F1
      type ATPases, with which Rho shares a number of structural features.

PMID- 9756882
TI  - A point mutation (G338S) and its suppressor mutations affect both the pH response
      of the NhaA-Na+/H+ antiporter as well as the growth phenotype of Escherichia
      coli.
AB  - pH controls the activity of the NhaA Na+/H+ antiporter of Escherichia coli. In
      the present work we show that replacement of glycine 338 of NhaA with serine
      (G338S) alleviates the pH control of the antiporter. Monitoring Na+-dependent
      collapse of DeltapH, to assess antiporter activity in isolated membrane vesicles,
      shows that the mutant protein is practically independent of pH, between pH 7 and
      9, and even at pH 6 is 70% active. Similarly the purified reconstituted mutant
      protein catalyzes pH-independent passive efflux of 22Na from proteoliposomes as
      well as DeltapH-driven influx. Whereas the native NhaA in isolated membrane
      vesicles is exposed to digestion by trypsin only above pH 7, the mutated protein
      is degraded already at pH 6.5. DeltanhaA DeltanhaB cells transformed with a
      plasmid encoding the pH-independent antiporter are sensitive to Na+ but not to K+
      at alkaline pH, while growing in the presence of both ions at neutral pH. Several
      possibilities that could explain the Na+ sensitivity of the mutant at alkaline pH
      were excluded; Western analysis and measurement of Na+/H+ antiporter activity in
      membrane vesicles, isolated from cells shifted to the non-permissive growth
      conditions, showed neither reduced expression of G338S-NhaA nor defective
      activity. The finding that the mutated protein is electrogenic led to the
      retraction of the idea that the protein is active in vitro but not in vivo at
      alkaline pH, when only Deltapsi exists in the cells. The Na+ concentration needed
      for half-maximal activity of G338S in isolated everted membrane vesicles is
      similar to that of the wild type. Therefore an increase in intracellular Na+ due
      to a reduced antiporter affinity could not explain the results. It is suggested
      that the loss of growth at alkaline pH in the presence of Na+ is due to the loss
      of the pH control of the mutated NhaA. Indeed, in the four mutations suppressing
      G338S phenotype, growth at alkaline pH was restored together with the pH
      regulation of NhaA. Three of the four suppressor mutations cluster in helix IV,
      whereas the original mutation is in helix XI, suggesting that the two helixes
      interact.

PMID- 9756884
TI  - Mechanism of angiotensin II-mediated regulation of fibronectin gene in rat
      vascular smooth muscle cells.
AB  - This study was performed to investigate a mechanism of angiotensin II (Ang II)
      mediated activation of the fibronectin (FN) gene in rat vascular smooth muscle
      cells. Actinomycin D and CV11974 completely inhibited Ang II-mediated increase in
      FN mRNA levels. Inhibitors of protein kinase C (PKC), protein-tyrosine kinase
      (PTK), phosphatidylinositol-specific phospholipase C, Ras, phosphatidylinositol 3
      kinase, p70 S6 kinase, and Ca2+/calmodulin kinase also decreased Ang II-induced
      activation of FN mRNA. In contrast, cycloheximide; PD123319; or inhibitors of Gi,
      protein kinase A, or mitogen-activated protein kinase kinase did not affect the
      induction. FN promoter contained a putative AP-1 binding site (rFN/AP-1; -463 to 
      437), and the results of a transient transfection and electrophoretic mobility
      shift assay showed that Ang II enhanced rFN/AP-1 activity. CV11974 and inhibitors
      of PKC or PTK suppressed Ang II-mediated increases in rFN/AP-1 activity, although
      neither PD123319 nor a protein kinase A inhibitor affected the induction.
      Furthermore, mutation of rFN/AP-1 that disrupted nuclear binding suppressed Ang
      II-induced transcription in the native FN promoter (-1908 to +136) context. Thus,
      Ang II activates transcription of the FN gene through the Ang II type 1 receptor
      in vascular smooth muscle cells, at least in part, via the activation of AP-1 by
      a signaling mechanism dependent on PKC and PTK.

PMID- 9756885
TI  - Protein farnesyltransferase from Trypanosoma brucei. A heterodimer of 61- and 65
      kda subunits as a new target for antiparasite therapeutics.
AB  - We have previously shown that protein prenylation occurs in the Trypanosomatids
      Trypanosoma brucei (T. brucei), Trypanosoma cruzi, and Leishmania mexicana and
      that protein farnesyltransferase (PFT) activity can be detected in cytosolic
      extracts of insect (procyclic) form T. brucei. A PFT that transfers the farnesyl
      group from farnesyl pyrophosphate to a cysteine that is 4 residues upstream of
      the C terminus of the Ras GTP-binding protein RAS1-CVIM has now been purified
      60,000-fold to near homogeneity from procyclic T. brucei. By screening a mixture
      of hexapeptides SSCALX (X is 20 different amino acids), it was found that SSCALM
      binds to T. brucei PFT with sub-micromolar affinity, and affinity chromatography
      using this peptide was a key step in the purification of this enzyme. On SDS
      polyacrylamide gel electrophoresis, the enzyme migrates as a pair of bands with
      apparent molecular masses of 61 and 65 kDa, and thus its subunits are
      approximately 30% larger than those of the mammalian homolog. The 61-kDa band was
      identified as the putative beta-subunit by photoaffinity labeling with a 32P
      labeled analog of farnesyl pyrophosphate. Mimetics of the C-terminal tetrapeptide
      of prenyl acceptors have been previously shown to inhibit mammalian PFT, and
      these compounds also inhibit T. brucei PFT with affinities in the nanomolar to
      micromolar range, although the structure-activity relationship is very different
      for parasite versus mammalian enzyme. Unlike mammalian cells, the growth of
      bloodstream T. brucei is completely inhibited by low micromolar concentrations of
      two of the PFT inhibitors, and these compounds also block protein farnesylation
      in cultured parasites. These compounds also potently block the growth of the
      intracellular (amastigote) form of T. cruzi grown in fibroblast host cells. The
      results suggest that protein farnesylation is a target for the development of
      anti-trypanosomatid chemotherapeutics.

PMID- 9756886
TI  - Purification, characterization, and kinetic mechanism of cyclin D1. CDK4, a major
      target for cell cycle regulation.
AB  - The cyclin D1.CDK4-pRb (retinoblastoma protein) pathway plays a central role in
      the cell cycle, and its deregulation is correlated with many types of cancers. As
      a major drug target, we purified dimeric cyclin D1.CDK4 complex to near
      homogeneity by a four-step procedure from a recombinant baculovirus-infected
      insect culture. We optimized the kinase activity and stability and developed a
      reproducible assay. We examined several catalytic and kinetic properties of the
      complex and, via steady-state kinetics, derived a kinetic mechanism with a
      peptide (RbING) and subsequently investigated the mechanistic implications with a
      physiologically relevant protein (Rb21) as the phosphoacceptor. The complex bound
      ATP 130-fold tighter when Rb21 instead of RbING was used as the phosphoacceptor.
      By using staurosporine and ADP as inhibitors, the kinetic mechanism of the
      complex appeared to be a "single displacement or Bi-Bi" with Mg2+.ATP as the
      leading substrate and phosphorylated RbING as the last product released. In
      addition, we purified a cyclin D1-CDK4 fusion protein to homogeneity by a three
      step protocol from another recombinant baculovirus culture and observed similar
      kinetic properties and mechanisms as those from the complex. We attempted to
      model staurosporine in the ATP-binding site of CDK4 according to our kinetic
      data. Our biochemical and modeling data provide validation of both the complex
      and fusion protein as highly active kinases and their usefulness in
      antiproliferative inhibitor discovery.

PMID- 9756888
TI  - Generation of specific deoxynojirimycin-type inhibitors of the non-lysosomal
      glucosylceramidase.
AB  - The existence of a non-lysosomal glucosylceramidase in human cells has been
      documented (van Weely, S., Brandsma, M., Strijland, A., Tager, J. M., and Aerts,
      J. M. F. G. (1993) Biochim. Biophys. Acta 1181, 55-62). Hypothetically, the
      activity of this enzyme, which is localized near the cell surface, may influence
      ceramide-mediated signaling processes. To obtain insight in the physiological
      importance of the non-lysosomal glucosylceramidase, the availability of specific
      inhibitors would be helpful. Here we report on the generation of hydrophobic
      deoxynojirimycin (DNM) derivatives that potently inhibit the enzyme. The
      inhibitors were designed on the basis of the known features of the non-lysosomal
      glucosylceramidase and consist of a DNM moiety, an N-alkyl spacer, and a large
      hydrophobic group that promotes insertion in membranes. In particular, N-(5
      adamantane-1-yl-methoxy)pentyl)-DNM is a very powerful inhibitor of the non
      lysosomal glucosylceramidase at nanomolar concentrations. At such concentrations,
      the lysosomal glucocerebrosidase and alpha-glucosidase, the glucosylceramide
      synthase, and the N-linked glycan-trimming alpha-glucosidases of the endoplasmic
      reticulum are not affected.

PMID- 9756887
TI  - Interaction of Hic-5, A senescence-related protein, with focal adhesion kinase.
AB  - Hydrogen peroxide-inducible clone (Hic)-5 is induced during the senescent process
      in human fibroblasts, and the overexpression of Hic-5 induces a senescence-like
      phenotype. Structurally, Hic-5 and paxillin, a 68-kDa cytoskeletal protein, share
      homology such as the LD motifs in the N-terminal half and the LIM domains in the
      C-terminal half. Here we show that Hic-5 binds to focal adhesion kinase (FAK) by
      its N-terminal domain, and is localized to focal adhesions by its C-terminal LIM
      domains. However, Hic-5 is not tyrosine phosphorylated either by the coexpressed
      FAK in COS cells or by integrin stimulation in 293T cells. Furthermore,
      overexpression of Hic-5 results in a decreased tyrosine phosphorylation of
      paxillin. These findings suggest that putative functions of Hic-5 are the
      recruitment of FAK to focal adhesions and a competitive inhibition of tyrosine
      phosphorylation of paxillin.

PMID- 9756889
TI  - Constitutive and adaptive detoxification of nitric oxide in Escherichia coli.
      Role of nitric-oxide dioxygenase in the protection of aconitase.
AB  - Nitric oxide (NO.) is a naturally occurring toxin that some organisms adaptively
      resist. In aerobic or anaerobic Escherichia coli, low levels of NO. exposure
      inactivated the NO.-sensitive citric acid cycle enzyme aconitase, and
      inactivation was more effective when the adaptive synthesis of NO.-defensive
      proteins was blocked with chloramphenicol. Protection of aconitase in aerobically
      grown E. coli was dependent upon O2, was potently inhibited by cyanide, and was
      correlated with an induced rate of cellular NO. consumption. Constitutive and
      adaptive cellular NO. consumption in aerobic cells was also dependent upon O2 and
      inhibited by cyanide. Exposure of aerobic cells to NO. accordingly elevated the
      activity of the O2-dependent and cyanide-sensitive NO. dioxygenase (NOD).
      Anaerobic E. coli exposed to NO. or nitrate induced a modest O2-independent and
      cyanide-resistant NO.-metabolizing activity and a more robust O2-stimulated
      cyanide-sensitive activity. The latter activity was attributed to NOD. The
      results support a role for NOD in the aerobic detoxification of NO. and suggest
      functions for NOD and a cyanide-resistant NO. scavenging activity in anaerobic
      cells.

PMID- 9756890
TI  - A regulatory element of the human keratin 18 gene with AP-1-dependent promoter
      activity.
AB  - The human keratin 18 (K18) gene is expressed in a restricted but diverse subset
      of differentiated epithelial tissues and carcinomas. The 10-kilobase pair K18
      gene contains all of the genetic information necessary for tissue-specific, copy
      number-dependent and integration site-independent expression in transgenic mice.
      We identified a 100-base pair regulatory element that activates the K18 proximal
      promoter in the presence of the previously identified first intron enhancer.
      Deletion of the element greatly diminished K18 expression. This regulatory
      element also has cryptic, AP-1-dependent promoter activity in the absence of the
      normal promoter, which results in 10-40-fold higher levels of K18 RNA expression
      in transgenic mice. The high activity of this cryptic promoter is dependent upon
      the first intron enhancer. These experiments define interactive regulatory
      regions of the K18 gene that modulate expression in diverse epithelial cell types
      and identify an unusual regulatory element with promoter activity that may be
      useful for high level heterologous gene expression in transgenic animals.

PMID- 9756891
TI  - Guanine nucleotide exchange on ADP-ribosylation factors catalyzed by cytohesin-1
      and its Sec7 domain.
AB  - ADP-ribosylation factors (ARFs) are 20-kDa guanine nucleotide-binding proteins
      that require specific guanine nucleotide-exchange proteins (GEPs) to accelerate
      the conversion of inactive ARF-GDP to active ARF-GTP. Cytohesin-1, a 46-kDa ARF
      GEP, contains a central Sec7 domain of 188 amino acids similar in sequence to a
      region of the yeast Sec7 protein. Cytohesin-1 and its 22-kDa Sec7 domain (C-1
      Sec7), synthesized in Escherichia coli, were assayed with recombinant non
      myristoylated ARFs and related proteins to compare their GEP activities. Both
      were effective with native mammalian ARFs 1 and 3. Cytohesin-1 accelerated
      GTPgammaS (guanosine 5'-3-O-(thio)triphosphate) binding to recombinant human ARF1
      (rARF1), yeast ARF3, and ARD1 (a 64-kDa guanine nucleotide-binding protein
      containing a C-terminal ARF domain). In contrast, C-1 Sec7 enhanced GTPgammaS
      binding to recombinant human ARFs 1, 5, and 6; yeast ARFs 1, 2, and 3; ARD1; two
      ARD1 mutants that contain the ARF domain; and Delta13ARF1, which lacks the N
      terminal alpha-helix. Neither C-1 Sec7 nor cytohesin-1 increased GTPgammaS
      binding to human ARF-like ARL proteins 1, 2, and 3. Thus, ARLs, initially
      differentiated from ARFs because of their inability to activate cholera toxin,
      differ also in their failure to interact functionally with C-1 Sec7 or cytohesin
      1. As C-1 Sec7 was much less substrate-specific than cytohesin-1, it appears that
      structure outside of the Sec7 domain is important for ARF specificity. Data
      obtained with mutant ARF constructs are all consistent with the conclusion that
      the ARF N terminus is an important determinant of cytohesin-1 specificity.

PMID- 9756892
TI  - Molecular basis of V2 vasopressin receptor/Gs coupling selectivity.
AB  - The molecular mechanisms governing the coupling selectivity of G protein-coupled
      receptors activated by peptide ligands are not well understood. To shed light on
      this issue, we have used the Gq/11-linked V1a and the Gs-coupled V2 vasopressin
      peptide receptors as model systems. To explore the structural basis underlying
      the ability of the V2 receptor to selectively recognize Gs, we systematically
      substituted distinct V2 receptor segments (or single amino acids) into the V1a
      receptor and studied whether the resulting hybrid receptors gained the ability to
      mediate hormone-dependent cAMP production. This strategy appeared particularly
      attractive since hormone stimulation of the V1a receptor has virtually no effect
      on intracellular cAMP levels. Functional analysis of a large number of mutant
      receptors transiently expressed in COS-7 cells indicated that the presence of V2
      receptor sequence at the N terminus of the third intracellular loop is critical
      for efficient activation of Gs. More detailed mutational analysis of this
      receptor region showed that two polar V2 receptor residues, Gln225 and Glu231,
      play key roles in Gs recognition. In addition, a short sequence at the N terminus
      of the cytoplasmic tail was found to make an important contribution to V2
      receptor/Gs coupling selectivity. We also made the novel observation that the
      efficiency of V2 receptor/Gs coupling can be modulated by the length of the
      central portion of the third intracellular loop (rather than the specific amino
      acid sequence within this domain). These findings provide novel insights into the
      molecular mechanisms regulating peptide receptor/G protein coupling selectivity.

PMID- 9756893
TI  - Tra1p is a component of the yeast Ada.Spt transcriptional regulatory complexes.
AB  - The yeast Ada and TBP class of Spt proteins interact in multiple complexes that
      are required for transcriptional regulation. We have identified Tra1p as a
      component of these complexes through tandem mass spectrometry analysis of
      proteins that associate with Ngg1p/Ada3p. TRA1 is an essential gene and encodes a
      3744-amino acid protein that is a member of a group of proteins including the
      catalytic subunit of DNA-dependent protein kinase, ATM and TRRAP, with carboxyl
      terminal regions related to phosphatidylinositol 3-kinases. The interaction
      between Tra1p and Ada/Spt components was verified by the reciprocal
      coimmunoprecipitation of Ada2p and Tra1p from whole cell extracts in one or more
      complexes containing Spt7p. Tra1p cofractionated with Ngg1p and Spt7p through
      consecutive chromatography on Mono Q, DNA-cellulose, and Superose 6 columns.
      Binding of Tra1p to DNA-cellulose required Ada components. The association of
      Tra1p with two Ada.Spt complexes was suggested by its cofractionation with Ngg1p
      and Spt7p in two peaks on the Mono Q column. In the absence of Ada2p, the elution
      profile of Tra1p shifted to a distinct peak. Despite the similarity of Tra1p to a
      group of putative protein kinases, we have not detected protein kinase activity
      within immunoprecipitates of Tra1p or the Ada.Spt complexes.

PMID- 9756894
TI  - Conversion of procaspase-3 to an autoactivating caspase by fusion to the caspase
      2 prodomain.
AB  - Caspases are cysteine proteases that play an essential role in apoptosis. Initial
      activation of caspases defines the key step in apoptotic execution. Based on
      primary structure, caspases can be divided into two groups, those with long amino
      terminal prodomains (class I), and those with relatively short prodomains (class
      II). On overexpression in mammalian cells, class I caspases can induce cell death
      that is dependent on their autocatalytic activity. Recent studies suggest that
      the long prodomains in some class I caspases are able to mediate dimerization of
      procaspase molecules, thereby promoting autoprocessing. In this communication, we
      demonstrate that fusion of the prodomain of a class I caspase (Nedd2/caspase-2)
      with procaspase-3 greatly augments autocatalysis and apoptosis induction by the
      chimeric caspase-3 molecule. The chimeric caspase-3 molecules were able to form
      homodimers in Saccharomyces cerevisiae and were efficiently processed in
      transfected mammalian cells. These results provide direct evidence for a role of
      a class I caspase prodomain in caspase autoactivation and processing and
      establish a basis for functional hierarchy among the two classes of caspases.

PMID- 9756895
TI  - Characterization of the chicken CTCF genomic locus, and initial study of the cell
      cycle-regulated promoter of the gene.
AB  - CTCF is a multifunctional transcription factor encoded by a novel candidate tumor
      suppressor gene (Filippova, G. N., Lindblom, A., Meinke, L. J., Klenova, E. M.,
      Neiman, P. E., Collins, S. J., Doggett, N. D., and Lobanenkov, V. V. (1998) Genes
      Chromosomes Cancer 22, 26-36). We characterized genomic organization of the
      chicken CTCF (chCTCF) gene, and studied the chCTCF promoter. Genomic locus of
      chCTCF contains a GC-rich untranslated exon separated from seven coding exons by
      a long intron. The 2-kilobase pair region upstream of the major transcription
      start site contains a CpG island marked by a "Not-knot" that includes sequence
      motifs characteristic of a TATA-less promoter of housekeeping genes. When fused
      upstream of a reporter chloramphenicol acetyltransferase gene, it acts as a
      strong transcriptional promoter in transient transfection experiments. The
      minimal 180-base pair chCTCF promoter region that is fully sufficient to confer
      high level transcriptional activity to the reporter contains high affinity
      binding element for the transcription factor YY1. This element is strictly
      conserved in chicken, mouse, and human CTCF genes. Mutations in the core
      nucleotides of the YY1 element reduce transcriptional activity of the minimal
      chCTCF promoter, indicating that the conserved YY1-binding sequence is critical
      for transcriptional regulation of vertebrate CTCF genes. We also noted in the
      chCTCF promoter several elements previously characterized in cell cycle-regulated
      genes, including the "cell cycle-dependent element" and "cell cycle gene homology
      region" motifs shown to be important for S/G2-specific up-regulation of cdc25C,
      cdc2, cyclin A, and Plk (polo-like kinase) gene promoters. Presence of the cell
      cycle-dependent element/cell cycle gene homology region element suggested that
      chCTCF expression may be cell cycle-regulated. We show that both levels of the
      endogenous chCTCF mRNA, and the activity of the stably transfected chCTCF
      promoter constructs, increase in S/G2 cells.

PMID- 9756896
TI  - Site-specific core 1 O-glycosylation pattern of the porcine submaxillary gland
      mucin tandem repeat. Evidence for the modulation of glycan length by peptide
      sequence.
AB  - The sequence-specific O-linked core 1 ([R1, R2]-beta-Gal(1-3)-alpha-GalNAc-O
      Ser/Thr) glycosylation pattern has been quantitatively determined for 30 of the
      31 Ser/Thr residues in the 81-residue porcine submaxillary gland mucin tandem
      repeat. This was achieved by Edman amino acid sequencing of the isolated tandem
      repeat after selective removal of non-C3-substituted, peptide-linked GalNAc
      residues by periodate oxidation and subsequent trimming of the remaining
      oligosaccharides to peptide-linked GalNAc residues by mild
      trifluoromethanesulfonic acid/anisole treatment. The sequencing reveals 61%
      (range, 12-95%) of the peptide alpha-N-acetylgalactosamine (GalNAc) residues to
      be substituted by core 1 chains, a value in agreement with the carbon-13 NMR
      analysis of the native mucin. Residues with the lowest C3 substitution were
      typically clustered in regions of sequence with the highest densities of
      (glycosylated) serine or threonine. This suggests that the porcine beta3-Gal,
      core 1, transferase is sensitive to peptide sequence and/or neighboring core
      GalNAc glycosylation in vivo, in keeping with earlier in vitro enzymatic
      glycosylation studies (Granovsky, M., Blielfeldt, T., Peters, S., Paulsen, H.,
      Meldal, M., Brockhausen, J., and Brockhausen, I. (1994) Eur. J. Biochem. 221,
      1039-1046). These results demonstrate that the O-glycan structures in mucin
      domains are not necessarily uniformly distributed along the polypeptide core and
      that their lengths can be modulated by peptide sequence. The data further suggest
      that hydroxyamino acid spacing may contribute to the regulation of glycan length,
      thereby, providing a mechanism for maintaining an optimally expanded, protease
      resistant, mucin conformation.

PMID- 9756897
TI  - Identification of inhibitors of prohormone convertases 1 and 2 using a peptide
      combinatorial library.
AB  - A positional scanning synthetic peptide combinatorial library containing
      approximately 52 million hexapeptides was used to identify potential inhibitory
      peptides for recombinant mouse prohormone convertase 1 (PC1) and PC2 and to
      provide information on the specificity of these enzymes. The library surveys
      revealed that a P6 Leu, a P4 Arg, a P2 Lys, and a P1 Arg were most inhibitory
      against PC1, and a P6 Ile and a P4 Arg were most inhibitory against PC2. Using
      information derived from the library surveys, hexapeptide sets were synthesized
      and screened for inhibition of PC1 and PC2. The data obtained revealed the
      preference of both enzymes for a P3 Val. At P5, many substitutions were well
      tolerated. PC1 and PC2 proved to differ mainly in the selectivity of their S6
      subsites. In PC1, this subsite displayed a strong preference toward occupation by
      Leu; the Ki value for peptide Ac-Leu-Leu-Arg-Val-Lys-Arg-NH2 was 28 times lower
      than that for peptide Ac-Ile-Ile-Arg-Val-Lys-Arg-NH2. In contrast, PC2
      discriminated little between Leu and Ile at P6, as evidenced by the small (1.5
      fold) difference in Ki values for these two peptides. Several hexapeptides
      synthesized as a result of the screen were found to represent potent inhibitors
      of PC2 (with Ki values in the submicromolar range) and, particularly, of PC1
      (with Ki values in the low nanomolar range). The most potent inhibitor, Ac-Leu
      Leu-Arg-Val-Lys-Arg-NH2, proved to be the same peptide for both enzymes and
      inhibited PC1 and PC2 in a competitive, fast-binding manner with Ki values of 3.2
      and 360 nM, respectively. The four most potent peptide inhibitors of PC1 and PC2
      were also tested against soluble human furin and found to exhibit a different
      rank order of inhibition; for example, Ac-Leu-Leu-Arg-Val-Lys-Arg-NH2 was 440
      fold less potent against furin than against PC1, with a Ki of 1400 nM.

PMID- 9756898
TI  - N-Methyl-D-aspartate inhibits apoptosis through activation of
      phosphatidylinositol 3-kinase in cerebellar granule neurons. A role for insulin
      receptor substrate-1 in the neurotrophic action of n-methyl-D-aspartate and its
      inhibition by ethanol.
AB  - Primary cultured rat cerebellar granule neurons underwent apoptosis when switched
      from medium containing 25 mM K+ to one containing 5 mM K+. N-methyl-D-aspartate
      (NMDA) protected granule neurons from apoptosis in medium containing 5 mM K+.
      Inhibition of apoptosis by NMDA was blocked by the phosphatidylinositol 3-kinase
      (PI 3-kinase) inhibitor LY294002, but it was unaffected by the mitogen-activated
      protein kinase kinase inhibitor PD 98059. The antiapoptotic action of NMDA was
      associated with an increase in the tyrosine phosphorylation of insulin receptor
      substrate 1 (IRS-1), an increase in the binding of the regulatory subunit of PI 3
      kinase to IRS-1, and a stimulation of PI 3-kinase activity. In the absence of
      extracellular Ca2+, NMDA was unable to prevent apoptosis or to phosphorylate IRS
      1 and activate PI 3-kinase. Significant inhibition of NMDA-mediated neuronal
      survival by ethanol (10-15%) was observed at 1 mM, and inhibition was half
      maximal at 45-50 mM. Inhibition of neuronal survival by ethanol corresponded with
      a marked reduction in the capacity of NMDA to increase the concentration of
      intracellular Ca2+, phosphorylate IRS-1, and activate PI 3-kinase. These data
      demonstrate that the neurotrophic action of NMDA and its inhibition by ethanol
      are mediated by alterations in the activity of a PI 3-kinase-dependent
      antiapoptotic signaling pathway.

PMID- 9756899
TI  - The role of residue 238 of TEM-1 beta-lactamase in the hydrolysis of extended
      spectrum antibiotics.
AB  - beta-Lactamases inactivate beta-lactam antibiotics by catalyzing the hydrolysis
      of the amide bond in the beta-lactam ring. The plasmid-encoded class A TEM-1 beta
      lactamase is a commonly encountered beta-lactamase. It is able to inactivate
      penicillins and cephalosporins but not extended-spectrum antibiotics. However,
      TEM-1-derived natural variants containing the G238S amino acid substitution
      display increased hydrolysis of extended-spectrum antibiotics. Two models have
      been proposed to explain the role of the G238S substitution in hydrolysis of
      extended-spectrum antibiotics. The first proposes a direct hydrogen bond of the
      Ser238 side chain to the oxime group of extended-spectrum antibiotics. The second
      proposes that steric conflict with surrounding residues, due to increased side
      chain volume, leads to a more accessible active site pocket. To assess the
      validity of each model, TEM-1 mutants with amino acids substitutions of Ala, Ser,
      Cys, Thr, Asn, and Val have been constructed. Kinetic analysis of these enzymes
      with penicillins and cephalosporins suggests that a hydrogen bond is necessary
      but not sufficient to achieve the hydrolytic activity of the G238S enzyme for the
      extended-spectrum antibiotics cefotaxime and ceftazidime. In addition, it appears
      that the new hydrogen bond interaction is to a site on the enzyme rather than
      directly to the extended-spectrum antibiotic. The data indicate that, for the
      G238S substitution, a combination of an optimal side chain volume and hydrogen
      bonding potential results in the most versatile and advantageous antibiotic
      hydrolytic spectrum for bacterial resistance to extended-spectrum antibiotics.

PMID- 9756900
TI  - Mechanism of action of RNA polymerase II elongation factor Elongin. Maximal
      stimulation of elongation requires conversion of the early elongation complex to
      an Elongin-activable form.
AB  - We previously identified and purified Elongin by its ability to stimulate the
      rate of elongation by RNA polymerase II in vitro (Bradsher, J. N., Jackson, K.
      W., Conaway, R. C., and Conaway, J. W. (1993) J. Biol. Chem. 268, 25587-25593).
      In this report, we present evidence that stimulation of elongation by Elongin
      requires that the early RNA polymerase II elongation complex undergoes conversion
      to an Elongin-activable form. We observe (i) that Elongin does not detectably
      stimulate the rate of promoter-specific transcription initiation by the fully
      assembled preinitiation complex and (ii) that early RNA polymerase II elongation
      intermediates first become susceptible to stimulation by Elongin after
      synthesizing 8-9-nucleotide-long transcripts. Furthermore, we show that the
      relative inability of Elongin to stimulate elongation by early elongation
      intermediates correlates not with the lengths of their associated transcripts
      but, instead, with the presence of transcription factor IIF (TFIIF) in
      transcription reactions. By exploiting adenovirus 2 major late promoter
      derivatives that contain premelted transcriptional start sites and do not require
      TFIIF, TFIIE, or TFIIH for transcription initiation, we observe (i) that Elongin
      is capable of strongly stimulating the rate of synthesis of trinucleotide
      transcripts by a subcomplex of RNA polymerase II, TBP, and TFIIB and (ii) that
      the ability of Elongin to stimulate synthesis of these short transcripts is
      substantially reduced by addition of TFIIF to transcription reactions. Here we
      present these findings, which are consistent with the model that maximal
      stimulation of elongation by Elongin requires that early elongation intermediates
      undergo a structural transition that includes loss of TFIIF.

PMID- 9756901
TI  - Molecular analysis of two pyruvate dehydrogenase kinases from maize.
AB  - Two maize cDNAs were isolated and sequenced that had open reading frames with
      approximately 37% amino acid identity to mammalian pyruvate dehydrogenase
      kinases. Both maize kinase sequences contain the five domains with conserved
      signature residues typical of procaryotic two-component histidine kinases.
      Sequence comparisons identified six other highly conserved motifs that are
      proposed to be specific to pyruvate dehydrogenase kinases. In addition, specific
      Trp and Cys residues are also invariant in these sequences. The maize cDNAs are
      1332 (PDK1) and 1602 (PDK2) nucleotides in length, encoding polypeptides with
      calculated molecular masses of 38,867 and 41,327 Da that share 77% amino acid
      identity. Reverse transcriptase-polymerase chain reaction analysis with
      oligonucleotide-specific primers revealed a differential expression pattern for
      the two isoforms. PDK1 and PDK2 were expressed in Escherichia coli with N
      terminal His6 tags to facilitate purification. The recombinant proteins migrated
      at 44 and 48 kDa, respectively, during SDS-polyacrylamide gel electrophoresis.
      Anti-PDK1 antibodies immunoprecipitated 75% of pyruvate dehydrogenase kinase
      activity from a maize mitochondrial matrix fraction, and recognized a matrix
      protein of 43 kDa. Recombinant PDK2, expressed as a fusion with the maltose
      binding protein, inactivated kinase-depleted maize pyruvate dehydrogenase complex
      when incubated with MgATP, coincident with incorporation of 32P from [gamma
      32P]ATP into the alpha subunit of pyruvate dehydrogenase.

PMID- 9756902
TI  - Functional assignment by Chimera construction of the domain affecting
      heterotropic activation of deoxyadenosine kinase from Lactobacillus acidophilus R
      26.
AB  - The heterodimeric subunits of deoxyadenosine kinase (dAK)-deoxyguanosine kinase
      (dGK) from Lactobacillus acidophilus R-26 exhibit contrasting conformations
      manifested in the nearly unidirectional heterotropic activation of dAK when dGK
      binds deoxyguanosine. This is mediated, in part, by the conserved Ras switch I
      like sequence (residues 153-161) [Guo et al. (1997) J. Biol. Chem. 272, 6890
      6897]. In an attempt to identify domains differentiating the specificities of dAK
      and dGK, we constructed several chimeras splicing heterodimeric dAK within this
      region. In Chimera-III, dAK residues 120-170 were replaced by the homologous
      section of dGK. dAK activity was elevated 40%, but although it retained its
      original specificity and Km values, it could no longer be activated by
      deoxyguanosine. Moreover, both the activated dAK and the "dAK" of Chimera-III
      exhibited (i) an increased Ks for the leading substrate ATP-Mg2+, suggesting the
      formation of intermediate enzyme species along their respective kinetic pathways,
      and (ii) broadened and lower pH optima for the dAK activities. These observations
      further indicate the importance of dAK residues 120-170, including the Ras-like
      segment, in catalysis and heterotropic activation. The other conformational
      properties of dAK (e.g. self-inactivity and MgATP being the leading substrate)
      were unaltered by this substitution, thus localizing the responsible domains even
      further upstream.

PMID- 9756903
TI  - Auxin-induced stress potentiates trans-activation by a conserved plant
      basic/leucine-zipper factor.
AB  - The promoter element activation sequence-1 (as-1) confers tissue-specific and
      signal-responsive transcription in plants. Hormone and chemical stress cues are
      thought to activate as-1-dependent transcription through specific basic/leucine
      zipper proteins, termed TGA factors, that bind this element. We report here that
      a highly conserved TGA factor of tobacco, TGA1a, can selectively activate
      transcription in response to micromolar concentrations of auxin hormones or their
      analogs. This induction is chemically specific, as a range of other compounds
      tested at similar concentrations had little or no effect. Auxin was found to
      augment the trans-activation potential of TGA1a through carboxyl-terminal
      residues. The amino-terminal domain of TGA1a, by gain-of-function assays, was
      found to both constitutively activate transcription and maximize the response to
      auxin. Further evidence indicates that the trans-activation potential of this
      domain in TGA1a is repressed, under basal conditions, by carboxyl-terminal
      residues. Because TGA1a and endogenous TGA factors are stimulated by auxin only
      at concentrations that inhibited cell growth, this response is likely to involve
      chemical stress.

PMID- 9756905
TI  - Solution structure of the epsilon subunit of the F1-ATPase from Escherichia coli
      and interactions of this subunit with beta subunits in the complex.
AB  - The solution structure of the epsilon subunit of the Escherichia coli F1-ATPase
      has been determined by NMR spectroscopy. This subunit has a two-domain structure
      with an N-terminal 10-stranded beta sandwich and a C-terminal antiparallel two
      alpha-helix hairpin, as described previously (Wilkens, S., Dahlquist, F. W.,
      McIntosh, L. P., Donaldson, L. W., and Capaldi, R. A. (1995) Nat. Struct. Biol.
      2, 961-967). New data show that the two domains interact in solution in an
      interface formed by beta strand 7 and the very C-terminal alpha-helix. This
      interface involves only hydrophobic interactions. The dynamics of the epsilon
      subunit in solution were examined. The two domains are relatively tightly
      associated with little or no flexibility relative to one another. The epsilon
      subunit can exist in two states in the ECF1F0 complex depending on whether ATP or
      ADP occupies catalytic sites. Proteolysis of the epsilon subunit in solution and
      when bound to the core F1 complex indicates that the conformation of the
      polypeptide in solution closely resembles the conformation of epsilon when bound
      to the F1 in the ADP state. Chemical and photo-cross-linking show that the
      epsilon subunit spans and interacts with two beta subunits in the ADP state.
      These interactions are disrupted on binding of ATP + Mg2+, as is the interaction
      between the N- and C-terminal domains of the epsilon subunit.

PMID- 9756904
TI  - The role of phosphoinositide 3-kinase in taurocholate-induced trafficking of ATP
      dependent canalicular transporters in rat liver.
AB  - Recent studies indicate that wortmannin, a potent inhibitor of
      phosphatidylinositol (PI) 3-kinase, interferes with bile acid secretion in rat
      liver; taurocholate induces recruitment of ATP-dependent transporters to the bile
      canalicular membrane, and PI 3-kinase products are important in intracellular
      trafficking. We investigated the role of PI 3-kinase in bile acid secretion by
      studying the in vivo effect of taurocholate, colchicine, and wortmannin on bile
      acid secretion, kinase activity, and protein levels in canalicular membrane
      vesicle (CMV) and sinusoidal membrane vesicle (SMV) fractions from rat liver.
      Treatment of rats or perfusion of isolated liver with taurocholate significantly
      increased PI 3-kinase activity in both membrane fractions. Taurocholate increased
      protein content of ATP-dependent transporters, which were detected only in CMVs,
      whereas increased levels of p85 and a cell adhesion molecule, cCAM 105, were
      observed in both fractions. Colchicine prevented taurocholate-induced changes in
      all proteins studied, as well as the increase in PI 3-kinase activity in CMVs,
      but it resulted in further accumulation of PI 3-kinase activity, p85, and cCAM
      105 in SMVs. These results indicate that taurocholate-mediated changes involve a
      microtubular system. Wortmannin blocked taurocholate-induced bile acid secretion.
      The effect was more profound when wortmannin was administered prior to treatment
      with taurocholate. When wortmannin was given after taurocholate, the protein
      levels of each ATP-dependent transporter were maintained in CMVs, whereas the
      levels of p85 and cCAM decreased in both membrane fractions. Perfusion of liver
      with wortmannin before taurocholate administration blocked accumulation of all
      proteins studied in CMVs and SMVs. These results indicate that PI 3-kinase is
      required for intracellular trafficking of itself, as well as of ATP-dependent
      canalicular transporters.

PMID- 9756906
TI  - Activation of the prolactin gene by peroxisome proliferator-activated receptor
      alpha appears to be DNA binding-independent.
AB  - Although the effects of the peroxisome proliferator-activated receptors (PPARs)
      have been studied primarily in adipocytes and liver, the wide distribution of
      these receptors suggests that they might also play a role in other cell types. We
      present evidence that PPAR activators stimulate the expression of the prolactin
      gene in pituitary GH4C1 cells. Transfection assays in non-pituitary HeLa cells
      showed that stimulation of the prolactin promoter by PPARalpha requires the
      presence of the transcription factor GHF-1 (or Pit-1). Proximal promoter
      sequences confer responsiveness to PPARalpha, and activation by this receptor is
      lost concomitantly with the response to GHF-1. Surprisingly, expression of the
      retinoid X receptor (RXR) abolishes stimulation by PPARalpha. Furthermore, the
      promoter region that confers PPARalpha responsiveness does not contain a PPAR
      response element. This suggests that the transcriptional effect of PPARalpha
      might be mediated by protein-protein interactions rather than by binding of
      PPAR/RXR to the promoter. A direct interaction between PPARalpha and GHF-1 was
      confirmed by in vitro binding studies. Expression of the coactivators SRC-1 and
      CREB-binding protein, which bind to PPAR, also enhanced the responsiveness of the
      prolactin promoter to PPARalpha. Furthermore, CREB-binding protein also
      significantly increased activation by GHF-1, and both proteins associated in
      vitro. Thus, PPARalpha, a receptor that normally acts as a ligand-dependent
      transcription factor by binding to specific DNA sequences in one context, can
      also stimulate the prolactin promoter by association with GHF-1 and coactivator
      proteins.

PMID- 9756907
TI  - Characterization of distinct human endometrial carcinoma cell lines deficient in
      mismatch repair that originated from a single tumor.
AB  - The role of specific mismatch repair (MMR) gene products was examined by
      observing several phenotypic end points in two MMR-deficient human endometrial
      carcinoma cell lines that were originally isolated from the same tumor. The first
      cell line, HEC-1-A, contains a nonsense mutation in the hPMS2 gene, which results
      in premature termination and a truncated hPMS2 protein. In addition, HEC-1-A
      cells carry a splice mutation in the hMSH6 gene and lack wild-type hMSH6 protein.
      The second cell line, HEC-1-B, possesses the same defective hMSH6 locus. However,
      HEC-1-B cells are heterozygous at the hPMS2 locus; that is, along with carrying
      the same nonsense mutation in hPMS2 as in HEC-1-A, HEC-1-B cells also contain a
      wild-type hPMS2 gene. Initial recognition of mismatches in DNA requires either
      the hMSH2/hMSH6 or hMSH2/hMSH3 heterodimer, with hPMS2 functioning downstream of
      damage recognition. Therefore, cells defective in hPMS2 should completely lack
      MMR (HEC-1-A), whereas cells mutant in hMSH6 only (HEC-1-B) can potentially
      repair damage via the hMSH2/hMSH3 heterodimer. The data presented here in HEC-1-B
      cells illustrate (i) the reduction of instability at microsatellite sequences,
      (ii) a significant decrease in frameshift mutation rate at HPRT, and (iii) the in
      vitro repair of looped substrates, relative to HEC-1-A cells, illustrating the
      repair of frameshift intermediates by hMSH2/hMSH3 heterodimer. Furthermore, the
      role of hMSH2/hMSH3 heterodimer in the repair of base:base mismatches is
      supported by observing the reduction in base substitution mutation rate at HPRT
      in HEC-1-B cells (hMSH6-defective but possessing wild-type hPMS2), as compared
      with HEC-1-A (hMSH6/hPMS2-defective) cells. These data support a critical role
      for hPMS2 in human MMR, while further defining the role of the hMSH2/hMSH3
      heterodimer in maintaining genomic stability in the absence of a wild-type
      hMSH2/hMSH6 heterodimer.

PMID- 9756908
TI  - Release of thioredoxin via the mechanosensitive channel MscL during osmotic
      downshock of Escherichia coli cells.
AB  - Escherichia coli cells possess several mechanosensitive ion channels but only
      MscL, the channel with the highest conductance, which is activated at the highest
      membrane tension, has been cloned. We investigated the putative involvement of
      MscL in the effluxes caused by osmotic downshock. Osmotic shock caused the
      release of potassium glutamate, trehalose, and glycine betaine from wild type
      cells and cells lacking MscL. There was no difference between the two strains,
      but the extreme rapidity of the efflux process, as shown herein for glycine
      betaine, suggests that it is channel-mediated. Osmotic downshock also induces the
      release of some cytosolic proteins from EDTA-treated cells. We investigated the
      release of thioredoxin. This protein was totally released from wild type cells
      but was retained by MscL- cells. Release was restored by expression of the gene
      coding for MscL. Thus MscL is not necessary for the excretion of osmoprotectants,
      but it does open in vivo during shock and catalyzes the efflux of thioredoxin and
      possibly other small cytosolic proteins. It follows that the other
      mechanosensitive channels, which are known to be activated at lower tension, must
      also open during osmotic shock. Their opening and that of MscL could account for
      the rapid release of osmolytes.

PMID- 9756909
TI  - Identification of three major sentrinization sites in PML.
AB  - Acute promyelocytic leukemia arises following a reciprocal chromosome
      translocation t(15;17), which generates PML-retinoic acid receptor alpha fusion
      proteins (PML-RARalpha). We have shown previously that wild type PML, but not PML
      RARalpha, is covalently modified by the sentrin family of ubiquitin-like proteins
      (Kamitani, T., Nguyen, H. P., Kito, K., Fukuda-Kamitani, T., and Yeh, E. T. H.
      (1998) J. Biol. Chem. 273, 3117-3120). To understand the mechanisms underlying
      the differential sentrinization of PML versus PML-RARalpha, extensive mutational
      analysis was carried out to determine which Lys residues are sentrinized. We show
      that Lys65 in the RING finger domain, Lys160 in the B1 Box, and Lys490 in the
      nuclear localization signal contributes three major sentrinization sites. The PML
      mutant with Lys to Arg substitutions in all three sites is expressed normally,
      but cannot be sentrinized. Furthermore, the triple substitution mutant is
      localized predominantly to the nucleoplasm, in contrast to wild type PML, which
      is localized to the nuclear bodies. Thus, sentrinization of PML, in the context
      of the RING finger and the B1 box, regulates nuclear body formation. Furthermore,
      we showed that sentrinization of PML-RARalpha could be restored by overexpression
      of sentrin, but not by retinoic acid treatment. These studies provide novel
      insight into the pathobiochemistry of acute promyelocytic leukemia and the
      sentrinization pathway.

PMID- 9756910
TI  - Characterization of a 190-kilobase pair domain of human type I hair keratin
      genes.
AB  - Polymerase chain reaction-based screening of an arrayed human P1 artificial
      chromosome (PAC) library using primer pairs specific for the human type I hair
      keratins hHa3-II or hHa6, led to the isolation of two PAC clones, which covered
      190 kilobase pairs (kbp) of genomic DNA and contained nine human type I hair
      keratin genes, one transcribed hair keratin pseudogene, as well as one orphan
      exon. The hair keratin genes are 4-7 kbp in size, exhibit intergenic distances of
      5-8 kbp, and display the same direction of transcription. With one exception, all
      hair keratin genes are organized into 7 exons and 6 positionally conserved
      introns. On the basis of sequence homologies, the genes can be grouped into three
      subclusters of tandemly arranged genes. One subcluster harbors the highly related
      genes hHa1, hHa3-I, hHa3-II, and hHa4. A second subcluster of highly related
      genes comprises the novel genes hHa7 and hHa8, as well as pseudogene PsihHaA,
      while the structurally less related genes hHa6, hHa5, and hHa2 are constituents
      of the third subcluster. As shown by reverse transcription-polymerase chain
      reaction, all hair keratin genes, including the pseudogene, are expressed in the
      human hair follicle. The transcribed pseudogene PsihHaA contains a premature stop
      codon in exon 4 and exhibits aberrant pre-mRNA splicing. Evolutionary tree
      construction reveals an early divergence of hair keratin genes from cytokeratin
      genes, followed by the segregation of the genes into the three subclusters. We
      suspect that the 190-kbp domain contains the entire complement of human type I
      hair keratin genes.

PMID- 9756911
TI  - Physiological and pathological secretion of cartilage oligomeric matrix protein
      by cells in culture.
AB  - Abnormalities in cartilage oligomeric matrix protein (COMP), a pentameric
      structural protein of the cartilage extracellular matrix, have been identified in
      pseudoachondroplasia and multiple epiphyseal dysplasia, two human autosomal
      dominant osteochondrodysplasias. However, the function of the protein remains
      unknown. With the goal of establishing a model to study the mechanisms by which
      COMP mutations cause disease, we have analyzed synthesis and secretion of COMP in
      cultured chondrocytes, tendon, and ligament cells. Pentameric protein detected
      inside of control cells suggested that pentamerization is an intracellular
      process. Patient cells expressed mutant and normal RNA and secreted COMP at
      levels similar to controls, suggesting that abnormal pentamers are likely to be
      found in the extracellular matrix. Inclusions within patient cartilage stained
      with anti-COMP antibodies, and cultured cells presented similar inclusions,
      indicating that presumably abnormal COMP pentamers are less efficiently secreted
      than normal molecules. We conclude that the COMP disorders are likely to result
      from a combination of a decreased amount of COMP in the matrix and a dominant
      negative effect due to the presence of abnormal pentamers in cartilage.

PMID- 9756912
TI  - RP58 associates with condensed chromatin and mediates a sequence-specific
      transcriptional repression.
AB  - An approximately 120-amino acid domain present generally at the NH2 termini,
      termed the POZ domain, is highly conserved in various proteins with zinc finger
      DNA binding motifs. We have isolated a novel protein sharing homology with the
      POZ domain of a number of zinc finger proteins, including the human BCL-6
      protein. By using a binding site selection technique (CAST), a high affinity
      binding site of the protein was determined to be (A/C)ACATCTG(G/T)(A/C),
      containing the E box core sequence motif. The protein was shown to repress
      transcription from a promoter linked to its target sequences and was hence named
      RP58 (Repressor Protein with a predicted molecular mass of 58 kDa). Immunogold
      electron microscopic study revealed that almost all RP58 is localized in
      condensed chromatin regions. These observations demonstrate for the first time
      that a protein mediating a sequence-specific transcriptional repression
      associates with highly condensed chromatin. We suggest that RP58 may be involved
      in a molecular link between sequence-specific transcriptional repression and the
      organization of chromosomes in the nucleus.

PMID- 9756913
TI  - A pathway where polyprenyl diphosphate elongates in prenyltransferase. Insight
      into a common mechanism of chain length determination of prenyltransferases.
AB  - Prenyltransferases catalyze the consecutive condensations of isopentenyl
      diphosphate to produce linear polyprenyl diphosphates. Each enzyme forms the
      final product with a specific chain length. The product specificity of an enzyme
      is thought to be determined by the structure around the unknown path through
      which the product elongates in the enzyme. To explore the path, we introduced a
      few mutations at the 5th, the 8th, and/or the 11th positions before the first
      aspartate-rich motif of geranylgeranyl-diphosphate synthase or farnesyl
      diphosphate synthase. The side chains of these amino acids are situated on the
      same side of an alpha-helix. In geranylgeranyl-diphosphate synthase, a single
      mutated enzyme (F77S) mainly produces a C25 product (Ohnuma, S.-I., Hirooka, K.,
      Hemmi, H., Ishida, C., Ohto, C., and Nishino, T. (1996) J. Biol. Chem. 271, 18831
      18837). A double mutated enzyme (L74G and F77G) mainly produces a C35 compound
      with significant amounts of C30 and C40. A triple mutated enzyme (I71G, L74G, and
      F77G) mainly produces a C40 compound with C35 and C45. Mutated farnesyl
      diphosphate synthases also show similar patterns. These findings indicate that
      the elongating product passages on a surface of the side chains of the mutated
      amino acids, the original bulky amino acids had blocked the elongation, and the
      path is conserved in prenyltransferases. Moreover, the fact that some double and
      triple mutated enzymes can also form small amounts of products longer than C50
      indicates that the paths in these mutated enzymes can partially access the outer
      surface of the enzymes.

PMID- 9756914
TI  - X-ray analysis of the NMC-A beta-lactamase at 1.64-A resolution, a class A
      carbapenemase with broad substrate specificity.
AB  - The treatment of infectious diseases by penicillin and cephalosporin antibiotics
      is continuously challenged by the emergence and the dissemination of the numerous
      TEM and SHV mutant beta-lactamases with extended substrate profiles. These class
      A beta-lactamases nevertheless remain inefficient against carbapenems, the most
      effective antibiotics against clinically relevant pathogens. A new member of this
      enzyme class, NMC-A, was recently reported to hydrolyze at high rates, and hence
      destroy, all known beta-lactam antibiotics, including carbapenems and
      cephamycins. The crystal structure of NMC-A was solved to 1.64-A resolution, and
      reveals modifications in the topology of the substrate-binding site. While
      preserving the geometry of the essential catalytic residues, the active site of
      the enzyme presents a disulfide bridge between residues 69 and 238, and certain
      other structural differences compared with the other beta-lactamases. These
      unusual features in class A beta-lactamases involve amino acids that participate
      in enzyme-substrate interactions, which suggested that these structural factors
      should be related to the very broad substrate specificity of this enzyme. The
      comparison of the NMC-A structure with those of other class A enzymes and enzyme
      ligand complexes, indicated that the position of Asn-132 in NMC-A provides
      critical additional space in the region of the protein where the poorer
      substrates for class A beta-lactamases, such as cephamycins and carbapenems, need
      to be accommodated.

PMID- 9756915
TI  - Extracellular signal-regulated protein kinase/Jun kinase cross-talk underlies
      vascular endothelial cell growth factor-induced endothelial cell proliferation.
AB  - Ligand binding to vascular endothelial cell growth factor (VEGF) receptors
      activates the mitogen-activated protein kinases extracellular signal-regulated
      kinase (ERK) and c-Jun N-terminal protein kinase (JNK). Possible cross
      communication of ERK and JNK effecting endothelial cell (EC) actions of VEGF is
      poorly understood. Incubation of EC with PD 98059, a specific mitogen-activated
      protein kinase kinase inhibitor, or transfection with Y185F, a dominant negative
      ERK2, strongly inhibited VEGF-activated JNK. JNK was also activated by ERK2
      expression in the absence of VEGF, inhibited 82% by co-transfection with dominant
      negative SEK-1, indicating upstream activation of JNK by ERK. VEGF-stimulated JNK
      activity was also reversed by dominant negative SEK-1. Other EC growth factors
      exhibited similar cross-activation of JNK through ERK. VEGF stimulated the
      nuclear incorporation of thymidine, reversed 89% by PD 98059 and 72% by Y185F.
      Dominant negative SEK-1 or JNK-1 also significantly reduced VEGF-stimulated
      thymidine incorporation. Expression of wild type Jip-1, which prevents JNK
      nuclear translocation, inhibited VEGF-induced EC proliferation by 75%. VEGF
      stimulated both cyclin D1 synthesis and Cdk4 kinase activity, inhibited by PD
      98059 and dominant negative JNK-1. Important events for VEGF-induced G1/S
      progression and cell proliferation are enhanced through a novel ERK to JNK cross
      activation and subsequent JNK action.

PMID- 9756916
TI  - Expression cloning and characterization of a novel murine alpha1, 3
      fucosyltransferase, mFuc-TIX, that synthesizes the Lewis x (CD15) epitope in
      brain and kidney.
AB  - The 3-fucosyl-N-acetyllactosamine (Lewis x, CD15, SSEA-1) carbohydrate epitope is
      widely distributed in many tissues and is developmentally expressed in some
      rodent and human tissues, i.e. brain and lung, and mouse early embryo. In such
      tissues, the Lewis x epitope is considered to be involved in cell-cell
      interactions. We isolated a novel mouse alpha1,3-fucosyltransferase gene, named
      mFuc-TIX, from an adult mouse brain cDNA library using the expression cloning
      method. On flow cytometric analysis, Namalwa cells transfected stably with the
      mFuc-TIX gene showed a marked increase in Lewis x epitopes but not sialyl Lewis x
      epitopes. As seen experiments involving oligosaccharides as acceptor substrates,
      mFuc-TIX transfers a fucose to lacto-N-neotetraose but not to either alpha2,3
      sialyl lacto-N-neotetraose or lacto-N-tetraose. The substrate specificity of mFuc
      TIX was similar to that of mouse myeloid-type alpha1,3-fucosyltransferase (mFuc
      TIV). The deduced amino acid sequence of mFuc-TIX, consisting of 359 residues,
      indicated a type II membrane protein and shows low degrees of homology to the
      previously cloned alpha1,3-fucosyltransferases, i.e. mFuc-TIV (48.4%), mouse Fuc
      TVII (39.1%), and human Fuc-TIII (43.0%), at the amino acid sequence level. A
      phylogenetic tree of the alpha1, 3-fucosyltransferases constructed by the
      neighbor-joining method showed that mFuc-TIX is quite distant from the other
      alpha1, 3-fucosyltransferases. Thus, mFuc-TIX does not belong to any subfamilies
      of known alpha1,3Fuc-Ts. The mFuc-TIX transcript was mainly detected in brain and
      kidney with the Northern blotting and competitive reverse transcription
      polymerase chain reaction methods, whereas the mFuc-TIV transcript was not
      detected in brain with these methods. On in situ hybridization, the mFuc-TIX
      transcript was detected in neuronal cells but not in the glial cells including
      astrocytes. These results strongly indicated that mFuc-TIX participates in the
      Lewis x synthesis in neurons of the brain and may be developmentally regulated.

PMID- 9756917
TI  - Dissecting cAMP binding domain A in the RIalpha subunit of cAMP-dependent protein
      kinase. Distinct subsites for recognition of cAMP and the catalytic subunit.
AB  - The two gene-duplicated cAMP binding domains in the regulatory subunits of cAMP
      dependent protein kinase are each comprised of an A helix, an eight-stranded beta
      barrel, and a B and C helix (1). The A domain is required for high affinity
      binding to C, while the B domain regulates access to the A domain. Using a
      combination of a yeast two-hybrid screen coupled with deletion analysis, cAMP
      binding domain A of RI was dissected into two structurally and functionally
      distinct subsites, one that binds cAMP and another that binds the C subunit. The
      minimum stable subdomain required for binding to C in the 1-3 micromolar range is
      composed of residues 94-169, while residues 236-244, mapped to the C helix of
      cAMP binding domain A, were defined as a second surface necessary for high
      affinity (5-10 nanomolar) binding to C. This portion of the C helix, due to its
      position directly between the two subsites, serves as a molecular switch for
      either a cAMP-bound conformation or a C-bound conformation and can thus modulate
      interactions of cAMP binding domain A with cAMP, with C, and with cAMP binding
      domain B.

PMID- 9756918
TI  - Identification of a form of acyl-CoA:cholesterol acyltransferase specific to
      liver and intestine in nonhuman primates.
AB  - The present study demonstrates that two different forms of the intracellular
      cholesterol esterification enzyme acyl-CoA:cholesterol acyltransferase (ACAT) are
      present in the nonhuman primate hepatocyte; one is similar to that originally
      cloned from human genomic DNA, here termed ACAT1, while a second gene product,
      termed ACAT2, is reported here. The primate ACAT2 gene product was cloned from an
      African green monkey liver cDNA library. Sequence analysis of an isolated, full
      length clone of ACAT2 cDNA identified an open reading frame encoding a 526-amino
      acid protein with essentially no sequence similarity to the ACAT1 cDNA over the N
      terminal 101 amino acids but with 57% identity predicted over the remaining 425
      amino acids. Transfection of the cloned ACAT2 cDNA into two different mammalian
      cell types resulted in the production of abundant ACAT activity which was
      sensitive to ACAT inhibitors. Northern blot analysis showed that the ACAT2 mRNA
      was expressed primarily in liver and intestine in monkeys. In contrast, ACAT1
      mRNA was expressed in almost all tissues examined. Topologic predictions from the
      amino acid sequence of ACAT2 indicates that it has seven trans-membrane domains
      in a configuration that places the putative active site of the enzyme in the
      lumen of the endoplasmic reticulum. This orientation of ACAT2 in the endoplasmic
      reticulum membrane, in addition to its expression only in liver and intestine,
      suggests that this enzyme may have as a primary function, the secretion of
      cholesteryl esters into apoB-containing lipoproteins.

PMID- 9756919
TI  - ACAT-2, a second mammalian acyl-CoA:cholesterol acyltransferase. Its cloning,
      expression, and characterization.
AB  - The synthesis of cholesterol esters by acyl-CoA:cholesterol acyltransferase
      (ACAT, EC 2.3.1.26) is an important component of cellular cholesterol
      homeostasis. Cholesterol ester formation also is hypothesized to be important in
      several physiologic processes, including intestinal cholesterol absorption,
      hepatic lipoprotein production, and macrophage foam cell formation in
      atherosclerotic lesions. Mouse tissue expression studies and the disruption of
      the mouse ACAT gene (Acact) have indicated that more than one ACAT exists in
      mammals and specifically that another enzyme is important in mouse liver and
      intestine. We now describe a second mammalian ACAT enzyme, designated ACAT-2,
      that is 44% identical to the first cloned mouse ACAT (henceforth designated ACAT
      1). Infection of H5 insect cells with an ACAT-2 recombinant baculovirus resulted
      in expression of a approximately 46-kDa protein in cell membranes that was
      associated with high levels of cholesterol esterification activity. Both ACAT-1
      and ACAT-2 also catalyzed the esterification of the 3beta-hydroxyl group of a
      variety of oxysterols. Cholesterol esterification activities for ACAT-1 and ACAT
      2 exhibited different IC50 values when assayed in the presence of several ACAT
      specific inhibitors, demonstrating that ACAT inhibitors can selectively target
      specific forms of ACAT. ACAT-2 was expressed primarily in mouse liver and small
      intestine, supporting the hypothesis that ACAT-2 contributes to cholesterol
      esterification in these tissues. The mouse ACAT-2 gene (Acact2) maps to
      chromosome 15 in a region containing a quantitative trait locus influencing
      plasma cholesterol levels. The identification and cloning of ACAT-2 will
      facilitate molecular approaches to understanding the role of ACAT enzymes in
      mammalian biology.

PMID- 9756920
TI  - Characterization of two human genes encoding acyl coenzyme A:cholesterol
      acyltransferase-related enzymes.
AB  - The enzyme acyl coenzyme A:cholesterol acyltransferase 1 (ACAT1) mediates sterol
      esterification, a crucial component of intracellular lipid homeostasis. Two
      enzymes catalyze this activity in Saccharomyces cerevisiae (yeast), and several
      lines of evidence suggest multigene families may also exist in mammals. Using the
      human ACAT1 sequence to screen data bases of expressed sequence tags, we
      identified two novel and distinct partial human cDNAs. Full-length cDNA clones
      for these ACAT related gene products (ARGP) 1 and 2 were isolated from a
      hepatocyte (HepG2) cDNA library. ARGP1 was expressed in numerous human adult
      tissues and tissue culture cell lines, whereas expression of ARGP2 was more
      restricted. In vitro microsomal assays in a yeast strain deleted for both
      esterification genes and completely deficient in sterol esterification indicated
      that ARGP2 esterified cholesterol while ARGP1 did not. In contrast to ACAT1 and
      similar to liver esterification, the activity of ARGP2 was relatively resistant
      to a histidine active site modifier. ARGP2 is therefore a tissue-specific sterol
      esterification enzyme which we thus designated ACAT2. We speculate that ARGP1
      participates in the coenzyme A-dependent acylation of substrate(s) other than
      cholesterol. Consistent with this hypothesis, ARGP1, unlike any other member of
      this multigene family, possesses a predicted diacylglycerol binding motif
      suggesting that it may perform the last acylation in triglyceride biosynthesis.

PMID- 9756921
TI  - Activation of cyclin-dependent kinase 2 (Cdk2) in growth-stimulated rat
      astrocytes. Geranylgeranylated Rho small GTPase(s) are essential for the
      induction of cyclin E gene expression.
AB  - The role of the mevalonate cascade in the control of cell cycle progression in
      astrocytes has been investigated. Serum stimulation of rat astrocytes in primary
      culture induces the expression of cyclin E followed by the activation of cyclin
      dependent kinase 2 (Cdk2) during G1/S transition. The expression of p27, cyclin
      D1, and the activities of Cdk4 and Cdk-activating kinase (CAK), composed of Cdk7
      and cyclin H, were not affected. Serum did, however, stimulate the expression of
      3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase mRNA at mid-G1 phase.
      Moreover, an inhibitor of HMG-CoA reductase, pravastatin, reduced cyclin E
      expression and Cdk2 activation and caused G1 arrest in the astrocytes. In
      contrast, mevalonate and its metabolite, geranylgeranylpyrophosphate (GGPP) but
      not farnesylpyrophosphate (FPP), reversed the inhibitory effects of pravastatin
      on cyclin E expression and Cdk2 activation and allowed G1/S transition. Rho small
      GTPase(s) were geranylgeranylated and translocated to membranes in the presence
      of GGPP during G1/S transition. The effect of GGPP on cyclin E expression was
      abolished by botulinum C3 exoenzyme, which specifically inactivates Rho. These
      data indicate that geranylgeranylated Rho small GTPase(s) are essential for the
      induction of cyclin E expression, Cdk2 activation, and G1/S transition in rat
      astrocytes.

PMID- 9756922
TI  - Single glycosyltransferase, core 2 beta1-->6-N-acetylglucosaminyltransferase,
      regulates cell surface sialyl-Lex expression level in human pre-B lymphocytic
      leukemia cell line KM3 treated with phorbolester.
AB  - Sialyl-Lex (sLex) antigen expression recognized by KM93 monoclonal antibody was
      significantly down-regulated during differentiation induced by 12-O
      tetradecanoylphorbol-13-acetate (TPA) in human pre-B lymphocytic leukemia cell
      line KM3. The sLex determinants were almost exclusively expressed on O-linked
      oligosaccharide chains of an O-glycosylated 150-kDa glycoprotein (gp150). A low
      shear force cell adhesion assay showed that TPA treatment significantly inhibited
      E-selectin-mediated cell adhesion. Transcript and/or enzyme activity levels of
      alpha1-->3-fucosyltransferase, alpha2-->3-sialyltransferase, beta1-->4
      galactosyltransferase, and elongation beta1-->3-N-acetylglucosaminyltransferase
      did not correlate with sLex expression levels. However, transcript and enzyme
      activity levels of core 2 GlcNAc-transferase (C2GnT) were significantly down
      regulated during TPA treatment. Following transfection and constitutive
      expression of full-length exogenous C2GnT transcript, C2GnT enzyme activities
      were maintained at high levels even after TPA treatment and down-regulation of
      cell surface sLex antigen expression by TPA was completely abolished.
      Furthermore, in the transfected cells, the KM93 reactivity of gp150 was not
      reduced by TPA treatment, and the inhibition of cell adhesion by TPA was also
      blocked. These results suggest that sLex expression is critically regulated by a
      single glycosyltransferase, C2GnT, during differentiation of KM3 cells.

PMID- 9756923
TI  - Molecular analysis of the interactions between protein kinase C-epsilon and
      filamentous actin.
AB  - Protein kinase C-epsilon (PKC-epsilon) contains a putative actin binding motif
      that is unique to this individual member of the PKC gene family. We have used
      deletion mutagenesis to determine whether this hexapeptide motif is required for
      the physical association of PKC-epsilon and actin. Full-length recombinant PKC
      epsilon, but not PKC-betaII, -delta, -eta, or -zeta, bound to filamentous actin
      in a phorbol ester-dependent manner. Deletion of PKC-epsilon amino acids 222-230,
      encompassing a putative actin binding motif, completely abrogated this binding
      activity. When NIH 3T3 cells overexpressing either PKC-epsilon or the deletion
      mutant of this isozyme were treated with phorbol ester only wild-type PKC-epsilon
      colocalized with actin in zones of cell adhesion. In binary reactions, it was
      possible to demonstrate that purified filamentous actin is capable of directly
      stimulating PKC-epsilon phosphotransferase activity. These and other findings
      support the hypothesis that a conformationally hidden actin binding motif in the
      PKC-epsilon sequence becomes exposed upon activation of this isozyme and
      functions as a dominant localization signal in NIH 3T3 fibroblasts. This protein
      protein interaction is sufficient to maintain PKC-epsilon in a catalytically
      active conformation.

PMID- 9756925
TI  - Human inter-alpha-trypsin inhibitor heavy chain H3 gene. Genomic organization,
      promoter analysis, and gene linkage.
AB  - To understand more about the human inter-alpha-trypsin inhibitor heavy chain H3
      (ITIH3) expression and the relationship between this gene and the family of other
      ITI heavy chain genes, an analysis of the structure of the ITIH3 gene and its
      promoter region was performed. This gene is a single copy gene, 14 kilobase pair
      in length and consists of 22 exons. ITIH3 shares highly conserved exon size and
      intron-exon borders with other ITI heavy chain genes. We determined that the
      human ITIH1, ITIH3, and ITIH4 genes are closely linked within a 45-kilobase pair.
      They are arranged in the order of H1-H3-H4, with the ITIH4 gene transcribed in
      the opposite direction. A model for the evolution of the ITI heavy chain gene
      family is presented that involves multiple rounds of gene duplication plus
      inversion events. The minimum promoter region (-135 to +75) is identified in
      HepG2 cells. The transient transfection study in various cell lines indicates
      that the activity of the ITIH3 promoter is not liver-specific. DNase I
      footprinting, mobility shift assays, and cotransfection experiments reveal a
      functional CCAAT/enhancer-binding protein site (C/EBP, -1344 to -1305) which
      interacts with C/EBPalpha and C/EBPbeta factors. The latter factors control the
      transcription of the ITIH3 gene positively.

PMID- 9756924
TI  - Expression and trans-synaptic regulation of P2x4 and P2z receptors for
      extracellular ATP in parotid acinar cells. Effects of parasympathetic
      denervation.
AB  - Trans-synaptic regulation of muscarinic, peptidergic, and purinergic responses
      after denervation has been reported previously in rat parotid acinar cells
      (McMillian, M. K., Soltoff, S. P., Cantley, L. C., Rudel, R., and Talamo, B. R.
      (1993) Br. J. Pharmacol. 108, 453-461). Characteristics of the ATP-mediated
      responses and the effects of parasympathetic denervation were further analyzed
      through assay of Ca2+ influx, using fluorescence ratio imaging methods, and by
      analysis of P2x receptor expression. ATP activates both a high affinity and a low
      affinity response with properties corresponding to the recently described P2x4
      and the P2z (P2x7)-type purinoceptors, respectively. Reverse transcription
      polymerase chain reaction analysis reveals mRNA for P2x4 as well as P2x7 subtypes
      but not P2x1, P2x2, P2x3, P2x5, or P2x6. P2x4 protein also is detected by Western
      blotting. Distribution of the two types of ATP receptor responses on individual
      cells was stochastic, with both high and low affinity responses on some cells,
      and only a single type of response on others. Sensitivity to P2x4-type activation
      also varied even among cells responsive to low concentrations of ATP.
      Parasympathetic denervation greatly enhanced responses, tripling the proportion
      of acinar cells with a P2x4-type response and increasing the fraction of highly
      sensitive cells by 7-fold. Moreover, P2x4 mRNA is significantly increased
      following parasympathetic denervation. These data indicate that sensitivity to
      ATP is modulated by neurotransmission at parasympathetic synapses, at least in
      part through increased expression of P2x4 mRNA, and suggest that similar
      regulation may occur at other sites in the nervous system where P2x4 receptors
      are widely expressed.

PMID- 9756926
TI  - Light-dependent activation of rod transducin by pineal opsin.
AB  - The pineal gland expresses a unique member of the opsin family (P-opsin; Max, M.,
      McKinnon, P. J., Seidenman, K. J., Barrett, R. K., Applebury, M. L., Takahashi,
      J. S., and Margolskee, R. F. (1995) Science 267, 1502-1506) that may play a role
      in circadian entrainment and photo-regulation of melatonin synthesis. To study
      the function of this protein, an epitope-tagged P-opsin was stably expressed in
      an embryonic chicken pineal cell line. When incubated with 11-cis-retinal, a
      light-sensitive pigment was formed with a lambdamax at 462 +/- 2 nm. P-opsin
      bleached slowly in the dark (t1/2 = 2 h) in the presence of 50 mM hydroxylamine.
      Purified P-opsin in dodecyl maltoside activated rod transducin in a light
      dependent manner, catalyzing the exchange of more than 300 mol of GTPgammaS
      (guanosine 5'-O-(3-thiotriphosphate))/mol of P-opsin. The initial rate for
      activation (75 mol of GTPgammaS bound/mol of P-opsin/min at 7 microM) increased
      with increasing concentrations of transducin. The addition of egg
      phosphatidylcholine to P-opsin had little effect on the activation kinetics;
      however, the intrinsic rate of decay in the absence of transducin was
      accelerated. These results demonstrate that P-opsin is an efficient catalyst for
      activation of rod transducin and suggest that the pineal gland may contain a
      rodlike phototransduction cascade.

PMID- 9756927
TI  - Substrate binding induces depolymerization of the C-terminal peptide binding
      domain of murine GRP78/BiP.
AB  - To investigate the role of each domain in BiP/GRP78 function, we have used a full
      length recombinant BiP engineered to contain two enterokinase sites; one site is
      located after an N-terminal FLAG epitope, and a second site has been inserted at
      the junction between the N- and C-terminal domains (FLAG-BiP.ent). FLAG-BiP.ent
      oligomerizes into multiple species that interconvert with each other in a slow,
      concentration- and temperature-dependent equilibrium. Binding of ATP or AMP-PNP
      (adenosine 5'-(beta, gamma-imino)triphosphate), but not ADP, or of a peptidic
      substrate induces depolymerization of FLAG-BiP.ent and stabilization of monomeric
      species. Enterokinase cleavage of monomeric, nucleotide-free BiP.ent results in
      the physical dissociation of the 44-kDa N-terminal ATPase fragment (N44.ent) from
      the 30-kDa C-terminal substrate binding domain (C30.ent). Upon dissociation, the
      freed C-terminal substrate binding domain readily undergoes self-association
      while N44.ent remains monomeric. Enterokinase cleavage performed in the presence
      of a synthetic peptide prevents oligomerization of the freed C30.ent domain.
      Addition of ATP during enterokinase cleavage has no effect on C30.ent
      oligomerization. Our data clearly indicate that binding of a specific peptide
      onto the C-terminal domain, or ATP onto the N-terminal domain, induces internal
      conformational change(s) within the C30 domain that result(s) in BiP
      depolymerization.

PMID- 9756928
TI  - Identification of the MNN2 and MNN5 mannosyltransferases required for forming and
      extending the mannose branches of the outer chain mannans of Saccharomyces
      cerevisiae.
AB  - The mannan structure found on the N-linked glycans of the yeast Saccharomyces
      cerevisiae is composed of a long backbone of alpha-1, 6-linked mannose to which
      are attached branches consisting of two alpha-1,2-linked mannoses followed by an
      alpha-1,3-linked mannose. In the mutants mnn2 and mnn5, the addition of the first
      and second of these two mannoses, respectively, is defective. In this paper, we
      report the identification of the genes corresponding to these mutations. The two
      genes encode closely related proteins with distant homology to the known Mnn1p
      alpha-1,3-mannosyltransferase. We show that these proteins are localized in an
      early compartment of the yeast Golgi and that they are not physically associated
      with each other or with the two protein complexes known to be involved in
      synthesizing the alpha-1,6-linked backbone. The identification of Mnn2p and Mnn5p
      allows us to assign Golgi proteins to all of the catalytic steps in S. cerevisiae
      mannan synthesis.

PMID- 9756929
TI  - Functional analysis of human mitochondrial receptor Tom20 for protein import into
      mitochondria.
AB  - The mitochondrial import receptor translocase of the outer membrane of
      mitochondria (Tom20) consists of five segments, an N-terminal membrane-anchor
      segment, a linker segment rich in charged amino acids, a tetratricopeptide repeat
      motif, a glutamine-rich segment, and a C-terminal segment. To assess the role of
      each segment, four C-terminally truncated mutants of the human receptor (hTom20)
      were constructed, and the effect of their overexpression in COS-7 cells was
      analyzed. Expression of a mutant lacking the tetratricopeptide repeat motif
      inhibited preornithine transcarbamylase (pOTC) import to the same extent as the
      wild-type receptor. Thus, overexpression of the membrane-anchor and the linker
      segments is sufficient for the inhibition of import. Expression of either the
      wild-type receptor or a mutant lacking the C-terminal end of 20 amino acid
      residues stimulated import of pOTC-green fluorescent protein (GFP), a fusion
      protein in which the presequene of pOTC was fused to green fluorescent protein.
      On the other hand, expression of mutants lacking either the glutamine-rich
      segment or larger deletions inhibited pOTC-GFP import. In vitro import of pOTC
      was inhibited by the wild-type hTom20 and the mutant lacking the C-terminal end,
      but much less strongly by the mutant lacking the glutamine-rich segment. On the
      other hand, import of pOTC-GFP was little affected by any of the forms of hTom20.
      In binding assays, pOTC binding to hTom20 was only moderately decreased by the
      deletion of the glutamine-rich segment, whereas pOTC-GFP binding was completely
      lost by this deletion. Binding of pOTCN-GFP a construct that contains an
      additional 58 N-terminal residues of mature OTC, resembled that of pOTC. All of
      these results indicate that the region 106-125 containing the glutamine-rich
      segment of hTom20 is essential for binding and import stimulation in vivo of pOTC
      GFP and for inhibition of in vitro import of pOTC. The results also indicate that
      this region is important for mitochondrial aggregation. The different behaviors
      of pOTC and the pOTC-GFP chimera toward hTom20 mutants is explicable on the basis
      of the conformation of the precursor proteins.

PMID- 9756930
TI  - Activation of human endothelial cells via S-endo-1 antigen (CD146) stimulates the
      tyrosine phosphorylation of focal adhesion kinase p125(FAK).
AB  - S-Endo-1 antigen (CD146), a transmembrane receptor also known as MUC18/MCAM, is a
      member of the immunoglobulin superfamily and belongs to a group of cell adhesion
      molecules. CD146 is highly expressed on the whole vascular tree. We demonstrate
      here that engagement of CD146 on human endothelial cells isolated from cord blood
      results in tyrosine phosphorylation of a large panel of cellular proteins,
      although no tyrosine phosphorylation of CD146 was detected. In particular, CD146
      cross-linking induces the tyrosine phosphorylation of the protein tyrosine kinase
      p125(FAK) as well as p125(FAK) association with paxillin, both events being
      inhibited by cytochalasin D. No direct association of CD146 with p125(FAK) was
      observed. Consistent with these data, CD146 associates with p59(fyn), a Src
      family kinase known to phosphorylate p125(FAK). The identification of a signaling
      pathway initiated by CD146 engagement and which includes p59(fyn), p125(FAK), and
      paxillin indicates that CD146 participates in outside-in signaling in endothelial
      cells.

PMID- 9756931
TI  - Unique mode of GCC box recognition by the DNA-binding domain of ethylene
      responsive element-binding factor (ERF domain) in plant.
AB  - Ethylene-responsive element-binding proteins (EREBPs)have novel DNA-binding
      domains (ERF domains), which are widely conserved in plants, and interact
      specifically with sequences containing AGCCGCC motifs (GCC box). Deletion
      experiments show that some flanking region at the N terminus of the conserved 59
      amino acid ERF domain is required for stable binding to the GCC box. Three ERF
      domain-containing fragments of EREBP2, EREBP4, and AtERF1 from tobacco and
      Arabidopsis, bind to the sequence containing the GCC box with a high binding
      affinity in the pM range. The high affinity binding is conferred by a monomeric
      ERF domain fragment, and DNA truncation experiments show that only 11-base pair
      DNA containing the GCC box is sufficient for stable ERF domain interaction.
      Systematic DNA mutation analyses demonstrate that the specific amino acid
      contacts are confined within the 6-base pair GCCGCC region of the GCC box, and
      the first G, the fourth G, and the sixth C exhibit highest binding specificity
      common in all three ERF domain-containing fragments studied. Other bases within
      the GCC box exhibit modulated binding specificity varying from protein to
      protein, implying that these positions are important for differential binding by
      different EREBPs. The conserved N-terminal half is likely responsible for
      formation of a stable complex with the GCC box and the divergent C-terminal half
      for modulating the specificity.

PMID- 9756932
TI  - Tyrosine-based membrane protein sorting signals are differentially interpreted by
      polarized Madin-Darby canine kidney and LLC-PK1 epithelial cells.
AB  - Tyrosine-dependent sequence motifs are implicated in sorting membrane proteins to
      the basolateral domain of Madin-Darby canine kidney (MDCK) cells. We find that
      these motifs are interpreted differentially in various polarized epithelial cell
      types. The H, K-ATPase beta subunit, which contains a tyrosine-based motif in its
      cytoplasmic tail, was expressed in MDCK and LLC-PK1 cells. This protein was
      restricted to the basolateral membrane in MDCK cells, but was localized to the
      apical membrane in LLC-PK1 cells. Similarly, HA-Y543, a construct in which a
      tyrosine-based motif was introduced into the cytoplasmic tail of influenza
      hemagglutinin, was sorted to the basolateral membrane of MDCK cells and retained
      at the apical membrane of LLC-PK1 cells. A chimera in which the cytoplasmic tail
      of the H,K-ATPase beta subunit protein was replaced with the analogous region of
      the Na,K-ATPase beta subunit polypeptide was localized to both surface domains of
      MDCK cells. Mutation of tyrosine-20 of the H,K-ATPase beta subunit cytoplasmic
      sequence to an alanine was sufficient to disrupt basolateral localization of this
      polypeptide. In contrast, these constructs all remain localized to the apical
      membrane in LLC-PK1 cells. The FcRII-B2 protein bears a di-leucine motif and is
      found at the basolateral membrane of both MDCK and LLC-PK1 cells. These results
      demonstrate that polarized epithelia are able to discriminate between different
      classes of specifically defined membrane protein sorting signals.

PMID- 9756933
TI  - An essential role for autophosphorylation in the dissociation of activated
      protein kinase C from the plasma membrane.
AB  - The cellular localization of protein kinase C (PKC) is intimately associated with
      the regulation of its biological activity. Previously we have demonstrated that
      the redistribution of PKC to the plasma membrane in response to physiological
      stimuli is followed by a rapid returning of PKC back to the cytoplasm (Feng, X.,
      Zhang, J., Barak, L. S., Meyer, T., Caron, M. G., and Hannun, Y. A. (1998) J.
      Biol. Chem. 273, 10755-10762). Although the process of PKC membrane targeting has
      been extensively studied, the molecular mechanism underlying the dissociation of
      membrane-bound PKC remains unclear. In the present study, by examining the
      dynamic distribution of wild-type PKC betaII and its kinase-deficient mutant
      (K371R), we demonstrate that kinase activity is required for PKC membrane
      dissociation. Moreover, the inability of PKC betaII(K371R) to dissociate from the
      plasma membrane in cells overexpressing wild-type PKC betaII suggests that
      autophosphorylation activity of the kinase might be essential for its membrane
      dissociation. This was further supported by mutational analysis of two in vivo
      autophosphorylation sites on PKC betaII. The replacement of Ser660 or Thr641 by
      alanine (S660A or T641A) was found to synergistically reduce the reversal of PKC
      betaII membrane translocation, whereas the replacement of the same amino acids by
      glutamic acid (S660E or T641E), an amino acid commonly used to mimic phosphate,
      results in mutants behaving similar to wild-type PKC betaII. These findings point
      to an essential role for autophosphorylation in the dissociation of activated PKC
      from the plasma membrane and suggest that, like PKC membrane translocation, the
      returning of PKC to the cytoplasm after its activation is also delicately
      regulated.

PMID- 9756934
TI  - Transcriptional factor mutations reveal regulatory complexities of heat shock and
      newly identified stress genes in Saccharomyces cerevisiae.
AB  - A computer-aided pattern search of the entire yeast genome was designed and used
      to identify 186 putative stress response element-regulated genes in Saccharomyces
      cerevisiae. Transcript levels of eight of these candidate genes were examined,
      and three (37%) were shown to be heat shock- and DNA damage-inducible and to
      require the Msn2p and Msn4p transcriptional activators for stress regulation.
      Significantly, several heat shock protein (HSP) genes were identified in this
      computer search. Using a series of single and multiple regulatory mutants, we
      demonstrate unexpected regulatory complexities among the HSP genes from S.
      cerevisiae following heat shock.

PMID- 9756935
TI  - Dna2 of Saccharomyces cerevisiae possesses a single-stranded DNA-specific
      endonuclease activity that is able to act on double-stranded DNA in the presence
      of ATP.
AB  - To gain further insights into the biological functions of Dna2, previously known
      as a cellular replicative helicase in Saccharomyces cerevisiae, we examined
      biochemical properties of the recombinant Dna2 protein purified to homogeneity.
      Besides the single-stranded (ss) DNA-dependent ATPase activity as reported
      previously, we were able to demonstrate that ssDNA-specific endonuclease activity
      is intrinsically associated with Dna2. Moreover, Dna2 was capable of degrading
      duplex DNA in an ATP-dependent fashion. ATP and dATP, the only nucleotides
      hydrolyzed by Dna2, served to stimulate Dna2 to utilize duplex DNA, indicating
      their hydrolysis is required. Dna2 was able to unwind short duplex only under the
      condition where the endonuclease activity was minimized. This finding implies
      that Dna2 unwinds only partially the 3'-end of duplex DNA and generates a stretch
      of ssDNA of limited length, which is subsequently cleaved by the ssDNA-specific
      endonuclease activity. A point mutation at the conserved ATP-binding site of Dna2
      inactivated concurrently ssDNA-dependent ATPase, ATP-dependent nuclease, and
      helicase activities, indicating that they all reside in Dna2 itself. By virtue of
      its nucleolytic activities, the Dna2 protein may function in the maintenance of
      chromosomal integrity, such as repair or other related process, rather than in
      propagation of cellular replication forks.

PMID- 9756936
TI  - Biological activity and modular structure of RE-1-silencing transcription factor
      (REST), a repressor of neuronal genes.
AB  - The zinc finger protein RE-1-silencing transcription factor (REST)1 is a
      transcriptional repressor that represses neuronal genes in nonneuronal tissues.
      Transfection experiments of neuroblastoma cells using a REST expression vector
      revealed that synapsin I promoter activity is controlled by REST. The biological
      activity of REST was further investigated using a battery of model promoters
      containing strong promoters/enhancers and REST binding sites. REST functioned as
      a transcriptional repressor when REST binding motifs derived from the genes
      encoding synapsin I, SCG10, alpha1-glycine receptor, the beta2-subunit of the
      neuronal nicotinic acetylcholine receptor, and the m4-subunit of the muscarinic
      acetylcholine receptor were present in the promoter region. No differences in the
      biological activity of these REST binding motifs tested were detected. Moreover,
      we found that REST functioned very effectively as a transcriptional repressor at
      a distance. Thus, REST represents a general transcriptional repressor that blocks
      transcription regardless of the location or orientation of its binding site
      relative to the enhancer and promoter. This biological activity could also be
      attributed to isolated domains of REST. Both repressor domains identified at the
      N and C termini of REST were transferable to a heterologous DNA binding domain
      and functioned from proximal and distal positions, similar to the REST protein.

PMID- 9756937
TI  - Requirement of caspase-3(-like) protease-mediated hydrogen peroxide production
      for apoptosis induced by various anticancer drugs.
AB  - Caspase-3(-like) proteases play important roles in controlling mammalian
      apoptosis. However, the downstream events from the caspase-3(-like) protease
      activation to death of cells are still unclear. Previously, we reported that
      hydrogen peroxide (H2O2) was generated by the activation of caspase-3(-like)
      proteases in the process of tyrosine kinase inhibitor-induced apoptosis in human
      small cell lung carcinoma Ms-1 cells. In the present study, we examined whether
      generation of H2O2 is a critical event for the apoptotic pathway downstream of
      caspase-3(-like) protease activation by various anticancer drugs. Anticancer
      drugs such as camptothecin, vinblastine, inostamycin, and adriamycin induced
      activation of caspase-3(-like) proteases and apoptosis. Generation of H2O2 was
      commonly detected after treatment with each of the four anticancer drugs, and
      scavenging of H2O2 caused cells to fail to undergo apoptosis. Moreover,
      anticancer drug-induced H2O2 production was inhibited not only by an inhibitor of
      caspase-3(-like) proteases but also by diphenyleneiodonium chloride, an inhibitor
      of flavonoid-containing enzymes such as NADPH oxidase. However, activation of
      caspase-3(-like) proteases was not inhibited by diphenyleneiodonium chloride.
      These findings suggest that activation of caspase-3(-like) proteases by various
      anticancer drugs causes generation of H2O2 presumably through the activation of
      NADPH oxidase, thereby inducing apoptosis. Therefore, H2O2 may function as a
      common mediator for apoptosis induced by various anticancer drugs.

PMID- 9756938
TI  - The COOH-terminal tyrosine phosphorylation sites on IRS-1 bind SHP-2 and
      negatively regulate insulin signaling.
AB  - Activation of tyrosine kinases by numerous growth factor and cytokine receptors
      leads to tyrosine phosphorylation of the insulin receptor substrate (IRS)
      proteins. Tyrosine-phosphorylated motifs on the IRS proteins bind to the SH2
      domains in proteins that mediate downstream signals, including
      phosphatidylinositol 3'-kinase, GRB-2, and SHP-2. We investigated the function of
      the two SHP-2 binding COOH-terminal tyrosines of IRS-1 by replacing them with
      phenylalanine (IRS-1(FCT)). IRS-1(FCT) failed to bind SHP-2 or mediate its
      tyrosine phosphorylation during insulin stimulation. Although several reports
      suggest a critical role for SHP-2 in insulin stimulated mitogen-activated protein
      kinase activation and cell proliferation, IRS-1(FCT) mediated these effects
      normally in 32D cells. Indeed, IRS-1(FCT) exhibited increased tyrosine
      phosphorylation, phosphatidylinositol 3'-kinase binding and activation of protein
      synthesis in response to insulin. These results suggest that SHP-2 attentuates
      the phosphorylation and downstream signal transmission of IRS-1 and that the
      interaction of IRS-1 and SHP-2 is an important regulatory event which attenuates
      insulin metabolic responses.

PMID- 9756939
TI  - Overexpressed activated retinoid X receptors can mediate growth inhibitory
      effects of retinoids in human carcinoma cells.
AB  - Retinoic acid receptors (RARs) and retinoid X receptors (RXRs) mediate the
      effects of retinoids on gene expression by binding to response elements in
      retinoid-sensitive genes. RAR- but not RXR-selective retinoids were found in many
      previous studies to suppress the growth of various cells, implicating RXR-RAR in
      these effects. Using a co-expression vector for identifying cells that expressed
      retinoid receptors transiently and 5'-bromo-2'-deoxyuridine incorporation for
      labeling DNA-synthesizing cells, we found that RXR-selective retinoids inhibited
      DNA synthesis in squamous carcinoma 1483 cells transfected with RXRalpha but not
      with RARs. Ligand-induced transcription of the reporter luciferase gene via the
      activation of RXR-RXR but not RXR-RAR correlated with growth suppression. Studies
      with RXRalpha deletion mutants indicated that the DNA binding and the ligand
      binding domains are essential for mediating growth inhibition. A point mutation
      in the ligand binding domain (L430F) that decreased RXRalpha homodimerization
      compromised its growth inhibitory function. Further, RXRalpha mutant (F313A),
      which functions as a constitutively active receptor, inhibited DNA synthesis in
      the absence of ligand. These results demonstrate that RXR homodimer activation
      leads to growth inhibition and suggest that transfection of RXRalpha and
      treatment with RXR-selective retinoids or the transfection of constitutively
      activated RXRalpha mutant alone may have a therapeutic potential.

PMID- 9756940
TI  - The early growth response protein (EGR-1) regulates interleukin-2 transcription
      by synergistic interaction with the nuclear factor of activated T cells.
AB  - The early growth response-1 gene (EGR-1) is induced by a wide range of stimuli in
      diverse cell types; however, EGR-1-regulated genes display a highly restricted
      pattern of expression. Recently, an overlapping Sp1.EGR-1 binding site has been
      identified within the interleukin-2 (IL-2) gene promoter directly upstream of the
      binding site for the nuclear factor of activated T cells (NFAT). We used
      transfection assays to study how the abundantly and constitutively expressed Sp1
      protein and the immediate early EGR-1 zinc finger protein regulate IL-2 gene
      expression. Here, we identify EGR-1 as an important activator of the IL-2 gene.
      In Jurkat T cells, EGR-1 but not Sp1 acts as a potent coactivator for IL-2
      transcription, and in combination with NFATc, EGR-1 increases transcription of an
      IL-2 reporter construct 200-fold. Electrophoretic mobility shift assays reveal
      that recombinant EGR-1 and NFATc bind independently to their target sites within
      the IL-2 promoter, and the presence of both sites on the same DNA molecule is
      required for EGR-1.NFATc.DNA complex formation. The transcriptional synergy
      observed here for EGR-1 and NFATc explains how the abundant nuclear factor EGR-1
      contributes to the expression of restrictively expressed genes.

PMID- 9756941
TI  - Molecular role for the Rab binding platform of guanine nucleotide dissociation
      inhibitor in endoplasmic reticulum to Golgi transport.
AB  - Guanine nucleotide dissociation inhibitor (GDI) regulates the recycling of Rab
      GTPases involved in vesicle targeting and fusion. We have analyzed the
      requirement for conserved amino acid residues in the binding of Rab1A and the
      function of GDI in transport of cargo between the endoplasmic reticulum (ER) and
      the Golgi apparatus. Using a new approach to monitor GDI-Rab interactions based
      on the change in fluorescence associated with the release of methylanthraniloyl
      guanosine di(tri)phosphate-GDP (mGDP) from Rab, we show that residues previously
      implicated in the binding of the synapse-specific Rab3A, including Gln-236, Arg
      240, and Thr-248, are essential for the binding of Rab1A. Mutation of each of
      these residues has potent effects on the ability of GDI to remove Rab1A from
      membranes and inhibit ER to Golgi transport in vitro. Given the sequence
      divergence between Rab1A and 3A (35% identity), these residues are proposed to
      play a general role in GDI function in the cell. In contrast, several other
      residues found within or flanking the Rab-binding region were found to have
      differential effects in the recognition and recycling of Rab1A and 3A, and
      therefore direct selective interaction of GDI with individual Rab proteins.
      Intriguingly, mutation of one residue, Arg-70, led to a reduction of Rab1A
      binding, failed to extract Rab1A from membranes in vitro, yet bound membranes
      tightly and potently inhibited ER to Golgi transport. These results provide
      evidence that novel membrane-associated factor(s) mediate Rab-independent GDI
      interaction with membranes.

PMID- 9756942
TI  - Regulation of nucleoside transport by lipopolysaccharide, phorbol esters, and
      tumor necrosis factor-alpha in human B-lymphocytes.
AB  - Nucleoside transport systems and their regulation in human B-lymphocytes have
      been characterized using the cell lines Raji and Bare lymphoma syndrome-1 (BLS-1)
      as experimental models. These cells express at least three different nucleoside
      transport systems as follows: a nitrobenzylthioinosine-sensitive equilibrative
      transport system of the es-type, which appears to be associated with hENT1
      expression, and two Na+-dependent transport systems that may correspond to N1 and
      to the recently characterized N5-type, which is nitrobenzylthioinosine-sensitive
      and guanosine-preferring. B cell activators such as phorbol 12-myristate 13
      acetate and lipopolysaccharide (LPS) up-regulate both concentrative transport
      systems but down-regulate the equilibrative es-type transporter, which correlates
      with lower hENT1 mRNA levels. These effects are dependent on protein kinase C
      activity. Phorbol 12-myristate 13-acetate and LPS also induce an increase in
      tumor necrosis factor-alpha (TNF-alpha) mRNA levels, which suggest that this
      cytokine may mediate some of the effects triggered by these agents, since
      addition of TNF-alpha alone can increase N1 and N5 transport activities by a
      mechanism that also depends on protein kinase C activation. Interestingly, TNF
      alpha down-regulates es activity, but this effect cannot be abolished by
      inhibiting protein kinase C. This study reveals differential regulation of
      nucleoside transport systems following activation of human B-lymphocyte cell
      lines by agents of physiological relevance such as TNF-alpha and LPS. Moreover,
      it indicates that the recently characterized N5 transport system can also be
      regulated following B cell activation, which may be relevant to lymphocyte
      physiology and to the treatment of lymphocyte malignancies.

PMID- 9756943
TI  - Amino acid sequence requirement for efficient incorporation of
      glycosylphosphatidylinositol-associated proteins into the cell wall of
      Saccharomyces cerevisiae.
AB  - During cell wall biogenesis in Saccharomyces cerevisiae, some
      glycosylphosphatidylinositol (GPI)-attached proteins are detached from GPI
      moieties and bound to beta-1,6-glucan of the cell wall. The amino acid sequence
      requirement for the incorporation of GPI-attached proteins into the cell wall was
      studied by using reporter fusion proteins. Only the short omega-minus region
      composed of five amino acids, which is located upstream of the omega site for GPI
      attachment, determined the cellular localization of the GPI-associated proteins.
      Within the omega-minus region, amino acid residues at the omega-4 or -5 and omega
      2 sites were important for the cell wall incorporation. Yap3p, a well
      characterized GPI-anchored plasma membrane aspartic protease, was localized in
      the cell wall when the omega-minus region was mutated to sequences containing Val
      or Ile at the omega-4 or -5 site and Val or Tyr at the omega-2 site.

PMID- 9756944
TI  - Differential signaling by the epidermal growth factor-like growth factors
      neuregulin-1 and neuregulin-2.
AB  - The neuregulins comprise a subfamily of epidermal growth factor (EGF)-like growth
      factors that elicit diverse cellular responses by activating members of the ErbB
      family of receptor tyrosine kinases. Although neuregulin-1 and neuregulin-2 are
      both binding ligands for the ErbB3 and ErbB4 receptors, they exhibit distinct
      biological activities depending on cellular context. In MDA-MB-468 human mammary
      tumor cells, neuregulin-2beta (NRG2beta) inhibits cell growth, whereas neuregulin
      1beta (NRG1beta) does not. In these cells, NRG2beta appears to preferentially act
      through the EGF receptor, stimulating receptor tyrosine phosphorylation and the
      recruitment of phospholipase C-gamma, Cbl, SHP2, and Shc to that receptor.
      NRG1beta preferentially acts through ErbB3 in these cells by stimulating the
      tyrosine phosphorylation and recruitment of phosphatidylinositol 3-kinase and Shc
      to that receptor. In MDA-MB-453 cells, both NRG1beta and NRG2beta stimulate the
      tyrosine phosphorylation of the ErbB2 and ErbB3 receptors to similar extents, but
      only NRG1beta potently stimulates morphological changes consistent with their
      differentiation. The profiles of SH2 domain-containing proteins that are
      efficiently recruited to activated receptors differ for the two factors. These
      observations indicate that despite their overlapping receptor specificity, the
      neuregulins exhibit distinct biological and biochemical properties. Since both of
      these cell lines express only two of the known ErbB receptors, our results imply
      that EGF-like ligands might elicit differential signaling within the context of a
      single receptor heterodimer.

PMID- 9756945
TI  - Caveolin is an activator of insulin receptor signaling.
AB  - Recent data have demonstrated that caveolin, a major structural protein of
      caveolae, negatively regulates signaling molecules localized to caveolae. The
      interaction of caveolin with several caveolae-associated signaling proteins is
      mediated by the binding of the scaffolding region of caveolin to a hydrophobic
      amino acid-containing region within the regulated proteins. The presence of a
      similar motif within the insulin receptor kinase prompted us to investigate the
      caveolar localization and regulation of the insulin receptor by caveolin. We
      found that overexpression of caveolin-3 augmented insulin-stimulated
      phosphorylation of insulin receptor substrate-1 in 293T cells but not the
      phosphorylation of insulin receptor. Peptides corresponding to the scaffolding
      domain of caveolin potently stimulated insulin receptor kinase activity toward
      insulin receptor substrate-1 or a Src-derived peptide in vitro and in a caveolin
      subtype-dependent fashion. Peptides from caveolin-2 exhibited no effect, whereas
      caveolin-1 and -3 stimulated activity 10- and 17-fold, respectively. Peptides
      which increased insulin receptor kinase activity did so without affecting insulin
      receptor auto-phosphorylation. Furthermore, the insulin receptor bound to
      immobilized caveolin peptides, and this binding was inhibited in the presence of
      free caveolin-3 peptides. Thus, we have identified a novel mechanism by which the
      insulin receptor is bound and activated by specific caveolin subtypes.
      Furthermore, these data define a new role for caveolin as an activator of
      signaling.

PMID- 9756946
TI  - Down-regulation of cytochrome P450 1A1 gene promoter by oxidative stress.
      Critical contribution of nuclear factor 1.
AB  - Oxidative stress interferes with several cellular functions, in particular
      transcriptional regulation. We show here that the human cytochrome P450 1A1
      (CYP1A1) is down-regulated at the transcriptional level by oxidative stress.
      Basal as well as 2,3,7, 8-tetrachloro-p-dioxin-induced promoter activities are
      strongly impaired by H2O2 treatment or glutathione depletion with L-buthionine
      (S,R)-sulfoximine. Tumor necrosis factor alpha inhibits CYP1A1 expression, and
      this inhibition is prevented by the antioxidant pyrrolidine dithiocarbamate. We
      show that these regulations depend on the integrity of the nuclear factor 1 (NFI)
      site located in the proximal promoter. We therefore examined the redox regulation
      of this transcription factor. Treatment of human HepG2 or rat H4 hepatoma cells
      with H2O2 or L-buthionine-(S, R)-sulfoximine inactivates the binding of the NFI
      transcription factor to its DNA consensus sequence. Furthermore, H2O2 treatment
      leads to a dose-dependent decrease of reporter gene expressions driven by
      promoters containing NFI binding sites. Glutathione depletion and catalase
      inhibition also repress a NFI-driven promoter. Under the same conditions, the CP
      1 transcription factor activity is not affected by oxidative stress. Thus, NFI
      seems particularly sensitive to oxidative stress. This accounts, at least
      partially, for the regulation of cyp1A1 gene expression.

PMID- 9756947
TI  - Molecular cloning and characterization of RGC-32, a novel gene induced by
      complement activation in oligodendrocytes.
AB  - Sublytic complement activation on oligodendrocytes (OLG) down-regulates
      expression of myelin genes and induces cell cycle in culture. Differential
      display (DD) was used to search for new genes whose expression is altered in
      response to complement and that may be involved in cell cycle activation. DD
      bands showing either increased or decreased mRNA expression in response to
      complement were identified and designated Response Genes to Complement (RGC) 1
      32. RGC-1 is identical with heat shock protein 105, RGC-2 with poly(ADP-ribose)
      polymerase, and RGC-10 with IP-10. A new gene, RGC-32, that encodes a protein of
      137 amino acids was cloned. RGC-32 has no homology with other known proteins, and
      contains no motif that would indicate its function. In OLG, the mRNA expression
      was increased by complement activation and by terminal complement complex
      assembly. RGC-32 protein was localized in the cytoplasm and co-immunoprecipitated
      with cdc2 kinase. Overexpression of RGC-32 increased DNA synthesis in OLGxC6
      glioma cell hybrids. These results suggest that RGC-32 may play a role in cell
      cycle activation.

PMID- 9756948
TI  - Novel alternative splice variants of cGMP-binding cGMP-specific
      phosphodiesterase.
AB  - After our recent findings that the amino-terminal portion of rat cGMP-binding,
      cGMP-specific phosphodiesterase (cGB-PDE) differs from those of bovine and human
      cGB-PDEs, we found two forms of canine cGB-PDE cDNAs (CFPDE5A1 and CFPDE5A2) in
      canine lung. Each contained a distinct amino-terminal sequence, CFPDE5A1,
      possessing an amino-terminal portion with sequence similar to those of bovine and
      human, and CFPDE5A2, having one similar to that of rat. Other portions coding for
      the cGMP binding domains and the catalytic domain were conserved. Both CFPDE5A1
      and CFPDE5A2 transcripts were detected in the cerebellum, hippocampus, retina,
      lung, heart, spleen, and thoracic artery. CFPDE5A1 transcripts were particularly
      abundant in the pylorus, whereas CFPDE5A2 transcripts were quite low in this
      tissue. CFPDE5A1 and CFPDE5A2 expressed in COS-7 cells had cGMP Km values of 2.68
      and 1.97 microM, respectively, and both were inhibited by a low concentration of
      a cGB-PDE inhibitor, Zaprinast. Both CFPDE5A1 and CFPDE5A2 bound cGMP to their
      allosteric cGMP binding domains, and this cGMP binding was stimulated by 3
      isobutyl-1-methylxanthine. Thus, two types of alternative splice variants of
      canine cGB-PDE have been identified and shown to have similar biological
      properties in vitro.

PMID- 9756949
TI  - Regulation of actin binding and actin bundling activities of fascin by caldesmon
      coupled with tropomyosin.
AB  - Human fascin is an actin-bundling protein and is thought to play a role in the
      formation of microfilament bundles of microspikes and stress fibers in cultured
      cells. To explore the regulation of fascin-actin interaction, we have examined
      the effects of culture cell caldesmon and tropomyosin (TM) on actin binding
      activity of human fascin. Caldesmon alone or TM alone has little or no effect on
      the actin binding of fascin. However, caldesmon together with TM completely
      inhibits actin binding of human fascin. When calmodulin is added, the inhibition
      of fascin-actin interaction by caldesmon and TM becomes Ca2+ dependent because
      Ca2+/calmodulin blocks actin binding of caldesmon. Furthermore, as
      phosphorylation of caldesmon by cdc2 kinase inhibits actin binding of caldesmon,
      phosphorylation can also control actin binding of fascin in the presence of TM.
      As expected by the inhibition of fascin-actin binding, caldesmon coupled with TM
      also inhibits actin bundling activity of fascin. Whereas smooth muscle caldesmon
      alone or TM alone shows no effect, caldesmon together with TM completely inhibits
      actin bundling activity of fascin. This inhibition is again Ca2+ dependent when
      calmodulin is added to the system. These results suggest important roles for
      caldesmon and TM in the regulation of the function of human fascin.

PMID- 9756950
TI  - Transcriptional properties of RNA polymerase II within triplet repeat-containing
      DNA from the human myotonic dystrophy and fragile X loci.
AB  - Expansion of a (CTG)n segment within the 3'-untranslated region of the myotonic
      dystrophy protein kinase gene alters mRNA production. The inherent ability of RNA
      polymerase II to transcribe (CTG)17-255 tracts corresponding to DNA from normal,
      unstable, and affected individuals, and the normal (CGG)54 fragile X repeat
      tract, was analyzed using a synchronized in vitro transcription system. Core RNA
      polymerase II transcribed all repeat units irrespective of repeat length or
      orientation. However, approximately 50% of polymerases transiently halted
      transcription (with a half-life of approximately 10 +/- 1 s) within the first and
      second CTG repeat unit and a more transient barrier to elongation was observed
      roughly centered within repeats 6-9. Transcription within the remainder of the
      CTG tracts and within the CCG, CGG, and CAG tracts appeared uniform with average
      transcription rates of 170, 250, 300, and 410 nucleotides/min, respectively.
      These differences correlated with changes in the sequence-specific transient
      pausing pattern within the CNG repeat tracts; individual incorporation rates were
      slower after incorporation of pyrimidine residues. Unexpectedly, approximately 4%
      of the run-off transcripts were, depending on the repeat sequence, either 15 or
      18 nucleotides longer than expected. However, these products were not produced by
      transcriptional slippage within the repeat tract.

PMID- 9756951
TI  - Template end-to-end transposition by RNA polymerase II.
AB  - On 5'-template strand protruding templates, promoter-initiated run-off
      transcription by RNA polymerase II generates discrete, 15-16-nucleotide (nt)
      longer than expected products whose production is abrogated by elongation factor
      SII (Parsons, M. A., Sinden, R. R., and Izban, M. G. (1998) J. Biol. Chem. 273,
      26998-27008). We demonstrate that template terminal complexes produce these RNAs
      and that transcript extension is a general and salt-sensitive (250 mM) feature of
      run-off transcription. On 5'-overhung templates the extended run-off transcripts
      appear to be retained within an RNA-DNA-enzyme ternary complex, and SII
      facilitates resumption of transcript elongation via a dinucleotide truncation
      intermediate. Moreover, on one of the 5-overhung templates, the initially
      extended complexes spontaneously resumed transcript extension and were uniquely
      resistant to salt (250 mM) challenge. However, SII did not facilitate this long
      distance extension on all template ends. Run-off transcripts on a blunt-ended
      template were initially extended by 2-11 nt (roughly in 2-nt increments); SII
      addition either before or after extension resulted in the accumulation of a 4-5
      nt extension product. Based on these findings, we propose that the initial and
      continuously extended RNAs reflect intermediates and successful completion of
      template end-to-end transposition (template switching) by RNA polymerase II,
      respectively. Both the template end sequence and structure influenced the success
      of such an event.

PMID- 9756952
TI  - Structural requirements for in vivo myosin I function in Aspergillus nidulans.
AB  - We have investigated the minimal requirements of the tail region for myosin I
      function in vivo using the filamentous fungus Aspergillus nidulans. The CL3
      strain (McGoldrick, C. A., Gruver, C., and May, G. S. (1995) J. Cell Biol. 128,
      577-587) was transformed with a variety of myoA constructs containing mutations
      in the IQ, TH-1-like, SH3, and proline-rich domains by frameshift or in-frame
      deletions of the tail domains. The resulting strains contained wild type myoA
      driven by the alcA promoter and a mutant myoA driven by its endogenous promoter.
      This strategy allowed for selective expression of the wild type and/or mutant
      form of MYOA by the choice of growth medium. Proper septation and hyphal
      branching were found to be dependent on the interaction of the IQ motifs with
      calmodulin, as well as, the presence of its proline-rich domain. Additionally, a
      single proline-rich motif was sufficient for nearly wild type MYOA function. Most
      surprisingly, the SH3 domain was not essential for MYOA function. These studies
      expand our previous knowledge of the function of MYOA to include roles in hyphal
      morphogenesis, septal wall formation, and cell polarity, laying the groundwork
      for more detailed investigations on the function of the various tail domains in
      MYOA.

PMID- 9756953
TI  - The gene encoding the myeloid-related protein 14 (MRP14), a calcium-binding
      protein expressed in granulocytes and monocytes, contains a potent enhancer
      element in the first intron.
AB  - Myeloid-related proteins 8 and 14 (MRP8 and MRP14) are two Ca2+-binding proteins
      of the S-100 family highly abundant in myelomonocytic cells. The expression is
      not only dependent on the developmental status of the cell but also on the
      inflammatory situation in the tissue. In order to identify regulatory elements
      responsible for the high expression of MRP14 in myeloid cells, reporter gene
      constructs have been transfected into HL-60 cells, Mono Mac 6 cells, and L132
      cells. We demonstrated that a DNA element in the first intron (positions 153-361)
      enhances the transcriptional activity of the homologous promoter and of the
      heterologous herpes simplex virus thymidine kinase promoter up to 37-fold. To
      further identify the functional site, the region between positions 153 and 192
      was analyzed functionally using the thymidine kinase promoter. The region
      increased the expression in the same magnitude as the complete intron. This
      enhancer is highly conserved in the human and murine MRP genes, indicative of its
      involvement in the transcription of MRPs. Protein binding to the region is
      demonstrated using EMSA, DNA cross-linking, Southwestern blotting, and affinity
      purification. Affinity purification confirms that four proteins bind to the
      enhancer element.

PMID- 9756954
TI  - Quantitative in situ localization of tenascin-C alternatively spliced transcripts
      in the avian optic tectum.
AB  - PURPOSE: Tenascin-C is an extracellular matrix glycoprotein found at sites of
      embryonic cell motility, including the developing visual system. Numerous
      alternatively spliced variants of tenascin-C have been identified, and these
      variants have distinctive properties in vitro. The purpose of this study was to
      use quantitative in situ hybridization to determine the relative abundance of
      transcripts encoding the alternatively spliced fibronectin type III repeats of
      tenascin-C in the embryonic avian optic tectum. METHODS: Similarly sized DNA
      probes specific for sequences encoding the alternatively spliced repeats of
      tenascin-C were labeled with 35-S and applied to frozen sections of the E10 optic
      tectum. After determining the linear period of exposure, silver grain densities
      in the ventricular zone were calculated. RESULTS: Densitometric analysis revealed
      that more than half of the total tenascin-C mRNAs expressed in the ventricular
      zone of the E10 optic tectum encode the variable fibronectin type III repeats
      "A," "AD1" and "D." Transcripts encoding other variable repeats were detectable,
      but at considerably lower levels. CONCLUSIONS: The most abundant form of tenascin
      C in the developing optic tectum has a molecular weight of 230 kDa. Most of this
      form contains the variable repeats "A," "AD1," and "D," a combination of
      fibronectin type III repeats that has previously been identified only in a tumor
      derived cell line.

PMID- 9756955
TI  - Structural features of the aldose reductase and aldehyde reductase inhibitor
      binding sites.
AB  - The three-dimensional structures of aldose reductase and aldehyde reductase,
      members of the aldo-keto reductase superfamily, are composed of similar
      alpha/beta TIM-barrels. However, examination of the structures reveals that the
      inhibitor-binding site of aldose reductase differs from that of aldehyde
      reductase due to the participation of non-conserved residues in its formation.
      This information will be useful in the design of inhibitors to prevent or delay
      diabetic retinopathy. A review of the structures of the inhibitor-binding sites
      is presented.

PMID- 9756956
TI  - Biomechanical testing sequelae relevant to spinal fusion and instrumentation.
AB  - The increasing prevalence of spinal disorders and associated treatments has
      produced a dramatic increase in the number of available devices. The
      biomechanical evaluation leading to the design, development, and implementation
      of spinal instrumentation has resulted in a number of in vitro and in vivo
      testing methods. This article reviews some of the methods and associated results
      obtained by various evaluation techniques of spinal fusion hardware. Current work
      and future considerations also are presented.

PMID- 9756957
TI  - The use of diagnostic imaging to assess spinal arthrodesis.
AB  - Despite advances in surgical techniques and internal fixation devices,
      pseudarthrosis remains a significant factor in the clinical failure of attempted
      fusions in the cervical, thoracic, and lumbar spine. This article reviews the use
      of diagnostic imaging in the assessment of spinal fusion, with a focus on the
      accuracy of different imaging modalities based on surgical exploration. A cost
      effective strategy for the radiographic follow-up of patients after spinal fusion
      surgery also is presented.

PMID- 9756958
TI  - The biology of posterolateral lumbar spinal fusion.
AB  - This article reviews the existing knowledge base concerning the biology of spinal
      fusion, with the understanding that the focus is weighted toward posterolateral
      lumbar spinal fusion because of a relative paucity of biologic information on
      healing of other types of fusions. The discussion focuses first on the basic
      science of spinal fusion healing from the standpoint of animal modeling. Next,
      the discussion centers on the multitude of local factors that can affect fusion
      healing. Finally, the numerous systemic factors known to affect fusion healing
      are discussed.

PMID- 9756959
TI  - Biologic enhancement of spinal fusion.
AB  - Scientific advances in the past decade have generated considerable clinical
      interest in developing biologic tools that may ultimately enhance spinal fusion.
      This article reviews the current understanding of each of these and other fusion
      enhancing tools with particular attention to the results of in vivo animal
      experimentation and, where available, objective clinical data.

PMID- 9756960
TI  - Laparoscopic spinal fusion.
AB  - This article details the development of the laparoscopic technique of interbody
      spinal fusion. The rationale for this procedure is discussed as are indications,
      contraindications, and operative technique. The results of over 100 laparoscopic
      lumbar fusions are presented along with their complications and surgical
      recommendations.

PMID- 9756961
TI  - Percutaneous interbody fusions.
AB  - Percutaneous interbody fusion procedures have evolved as a result of the need for
      precise and specific access corridors to facilitate the application of technology
      to perform these procedures. Endoscopic visualization has expanded minimally
      invasive capabilities, particularly in the thoracic and lumbar spine. Refinement
      of grafting concepts and structural composition continues. Based on the
      historical evolution of the described percutaneous interbody fusion procedures,
      the future of minimally invasive interbody arthrodesis shows promise through the
      ongoing definition of access corridors and the refinement of operative tools and
      techniques.

PMID- 9756962
TI  - Laparoscopic bone dowel fusions of the lumbar spine.
AB  - Studies that show laparoscopic lumbar fusion to decrease cost or time of
      hospitalization or to increase the speed or incidence of return to activities are
      not currently available. Laparoscopic fusion of the lumbar spine appears to be a
      potentially attractive approach to treating axial back pain secondary to
      different causes. Although the technique is attractive because of its minimally
      invasive nature and marketing allure, it has yet to be established as to what the
      true clinical efficacy of this procedure will be. Further clinical study of these
      techniques with longer follow-up, and case-controlled studies should help
      clinicians to know the best fusion technique to offer patients.

PMID- 9756964
TI  - Complications of spinal fusion in adult patients more than 60 years of age.
AB  - This article describes the overall rate, characteristics, and predictive factors
      for major and minor complications in spinal fusion patients over 60 years of age
      (or greater) cared for in the authors' institution. Special emphasis is placed on
      establishing the most valid incidence of complications after spinal fusion by
      extracting the information directly from the pateint's permanent medical or
      clinical database record. Once the spinal surgery risk profile for the elderly
      patient is established, treatment interventions to modify these risks can be
      implemented and evaluated prospectively and longitudinally to maximize spinal
      surgery outcomes.

PMID- 9756963
TI  - Minimally invasive posterolateral lumbar arthrodesis.
AB  - Video-assisted and optical techniques have been adapted to minimally invasive
      approaches for lumbar arthrodesis. They hold the promise of improved outcomes and
      reduced morbidity, but development is recent and validation is limited.

PMID- 9756965
TI  - Complications in spinal fusion.
AB  - Complications in spinal fusion can lead to less than desirable results. The
      complications of spinal fusion in the cervical and lumbar spine are discussed.
      Methods of avoiding and correcting complications also are reviewed. Through a
      better understanding, it is hoped that complications can be prevented.

PMID- 9756966
TI  - Alternatives to spinal fusion.
AB  - Techniques have changed significantly with the advent of less invasive surgical
      techniques for disc excision and spinal fusion; these include the development of
      rigid internal fixation devices using multiple points of fixation and the better
      knowledge of the biology of spinal fusion. Despite these improvements in
      technology, room exists for alternative forms of surgical treatment because of
      significant failures particularly related to spinal fusions.

PMID- 9756967
TI  - Outcome assessment after spinal fusion: why and how?
AB  - Outcomes of medical interventions today must reflect a more complete array of
      measurements, including health status, patient satisfaction, medical costs, and
      quality of life. This article discusses the rationale and methodology involved
      with measurement of health status, particularly as it applies to spinal disorders
      and spinal fusion. Generic and disease-specific instruments are reviewed, and
      their limitations are also discussed.

PMID- 9756968
TI  - Indications and trends in use in cervical spinal fusions.
AB  - Anterior cervical decompression and arthrodesis has evolved over the last 40
      years and has become the preferred procedure for managing many cervical spine
      disorders. The first half of this article discusses the indications for cervical
      fusion in the management of traumatic, degenerative, neoplastic, infectious, and
      congenital conditions of the cervical spine. The second half of this article
      discusses the recent trends in use of cervical spine fusions that demonstrate the
      increasing frequency of this procedure in the United States over the last 10
      years.

PMID- 9756969
TI  - Cervical trauma: rationale for selecting the appropriate fusion technique.
AB  - The selection of the appropriate surgical approach in the management of an
      unstable cervical spine injury is predicated on the biomechanic deficiencies of
      the bony and ligamentous structures, the age of the patient, the level of
      experience of the surgeon, and the concomitant medical comorbidities. The optimal
      approach ideally is the least invasive, provides the greatest benefit-to-risk
      ratio in terms of potential injury to contiguous neurovascular structures, and
      provides adequate stabilization to avoid cumbersome external immobilization and
      allows early rehabilitation. This article discusses anterior, posterior, and
      combined stabilization techniques in patients who have sustained trauma to the
      upper and lower cervical spine.

PMID- 9756970
TI  - Cervical degenerative disease: rationale for selecting the appropriate fusion
      technique (Anterior, posterior, and 360 degree).
AB  - Many options exist for those treating cervical disc herniation, spondylosis, and
      deformity. This article examines the options for cervical degenerative fusions,
      the appropriate choice of technique (anterior, posterior, or combined
      anterior/posterior techniques), as well as bone graft and instrumentation
      choices.

PMID- 9756972
TI  - Clinical outcomes after cervical spine fusion.
AB  - The advent of sterile technique, modern anesthesia, and organized industrial
      society have allowed for great advances and widespread use of cervical
      arthrodesis for a variety of disorders. This article defines expected outcome for
      cervical arthrodesis used to treat degenerative disease, trauma, deformity, and a
      variety of other disorders.

PMID- 9756971
TI  - Cervical deformity: rationale for selecting the appropriate fusion technique
      (anterior, posterior, and 360 degree).
AB  - This article examines cervical deformities and their treatments, such as
      iatrogenic deformities, posttraumatic deformities, ankylosing spondylitis,
      rheumatoid arthritis, degenerative subaxial spondylolisthesis, myopathy,
      infectious spondylitis, and tumors. Congenital scoliosis and kyphosis and
      torticollis and rotatory atlanto-axial subluxation also are discussed.

PMID- 9756973
TI  - Indications for thoracic and lumbar spine fusion and trends in use.
AB  - Over the last 10 years, the annual number of spinal procedures performed in the
      United States has more than doubled. In 1996, there were roughly 29,000 thoracic
      or dorsal fusion procedures, which made up almost 13% of all spine fusions
      performed. Scoliosis was the most common condition necessitating posterior
      thoracic fusion. The first half of this article focuses on the indications for
      thoracic and lumbar fusions; whereas, the second half of this article discusses
      the trends in use of thoracic and lumbar spine fusions.

PMID- 9756974
TI  - Thoracic and lumbar trauma: rationale for selecting the appropriate fusion
      technnique.
AB  - Despite recent advances in surgical techniques and instrumentation, two issues in
      the treatment of thoracic and lumbar remain contested: (1) the indications for
      surgical intervention; and (2) the optimal approach to obtain decompression,
      realignment, and fusion of the disrupted segment (anterior, posterior, or
      combined). Choosing among the options requires the ability to define accurately
      the extent of the injury to both the structural and the neurologic elements of
      the spine as well as an appreciation of the historic rationale of individual
      treatment methods.

PMID- 9756975
TI  - Thoracic and lumbar fusions for degenerative disorders: rationale for selecting
      the appropriate fusion techniques.
AB  - This article defines the indications for spinal fusion surgery based on the
      current literature as well as a rationale for selecting the appropriate spinal
      fusion techniques for the more common degenerative lumbar and thoracic
      conditions.

PMID- 9756976
TI  - Thoracic and lumbar deformity: rationale for selecting the appropriate fusion
      technique (Anterior, posterior, and 360 degree).
AB  - The rationale of anterior versus posterior, or combined fusion is discussed with
      regards to different clinical diagnoses and situations. Factors involved in the
      decision-making process include stability, magnitude of deformity, rigidity of
      deformity, neurologic considerations, bone quality, and medical/metabolic
      factors. Careful preoperative assessment and planning are required as well as
      consideration for the patient's overall well being.

PMID- 9756977
TI  - Clinical outcome after fusion of the thoracic or lumbar spine in the adult
      patient.
AB  - This article highlights those disease processes for which fusion is used most
      frequently in the adult. Although the focus is on clinical outcome after fusion,
      the indications and natural history of the process itself are also briefly
      discussed to provide a comparative basis on which outcomes may be judged.

PMID- 9756979
TI  - Octanol-water partition: searching for predictive models.
AB  - The log n-octanol/water partition coefficient (log Po/w) still represents one of
      the most informative physicochemical parameters available to medicinal chemists.
      In the present work, principles, methodologies, and parameters are briefly
      reviewed for a variety of models developed to predict this parameter based on
      molecular structure. To include the developments of recent years, a total of more
      than 40 different approaches are mentioned with relevant bibliography within four
      major categories: group contribution methods, atomic contribution methods,
      molecular methods, and other physicochemical methods. To underscore once more the
      utility of this partition coefficient, a comprehensive and reevaluated
      correlation between log Po/w and in vivo permeability data of rat brain
      capillaries is included. Most deviants that fell below the trendline are those
      that have been recently found to be substrates for P-glycoprotein, a multidrug
      transporter that actively removes them from the brain. Accurate predictions of
      log Po/w may necessitate many parameters, but there is mounting evidence that
      molecular size and hydrogen bonding ability can account for a major part of the
      variance. Our recently developed, molecular size-based approach is reviewed, and
      it is argued that introduction of three-dimensionality allows the elimination of
      many empirically derived fragment constants without a significant deterioration
      of the predictive accuracy. A comparison of predictive power for six different
      methods on 145 molecules of interest for medicinal chemists is also included.

PMID- 9756978
TI  - 1 - 1. The chemistry and pharmacology of indole-3-carbinol (indole-3-methanol)
      and 3-(methoxymethyl)indole. [Part I].
AB  - Indole-3-carbinol (I3C) (2) is produced endogenously from naturally occurring
      glucosinolates contained in a wide variety of plant food substances including
      members of the family Cruciferae, and particularly members of the genus Brassica,
      whenever they are crushed or cooked. The acid environment of the gut very
      facilely converts it into a range of polyaromatic indolic compounds, e.g. (3,
      4,5), which appear to be responsible for many of the physiological effects
      observed following the ingestion of these foods. 3-(Methoxymethyl)indole (6) is
      formed with great ease whenever 2 contacts methylating agents, including
      methanol, and it is often found as a contaminant of 2. This contamination is
      often not recognized or easily removed because of the great similarities of the
      two in melting points and solubilities. However, their biological properties are
      essentially identical. These so-called chemopreventive compounds are important
      because of their enzyme induction and suppression, mutagenic, carcinogenic and,
      particularly, antimutagenic and anticarcinogenic properties. The natural
      occurrence, formation, preparation, identification, separation, quantification,
      chemical transformations and general toxicological properties of these substances
      are critically reviewed in detail in this paper of 146 references, the first of
      two parts. The enzyme induction and suppression, mutagenic, antimutagenic,
      mutagenic, anticarcinogenic and carcinogenic effects will be published later as
      Part II. At the present time it appears that these have considerable potential as
      natural prophylactic anticancer agents against certain common neoplasms,
      especially inasmuch modern diets are increasingly deficient in these vegetable
      derived substances.

PMID- 9756981
TI  - Biosynthetic anthracyclines.
AB  - This review summarizes the structure, the occurrence and the available data
      concerning the bioactivity of biosynthetic anthracyclines. The anthracyclines
      represent an important family of natural products produced by microorganisms of
      Streptomyces and related genera and include clinically useful agents for the
      medical treatment of human cancer. Chemically, the anthracyclines are glycosides
      characterized by a quinone tetracyclic aglycone and one or more deoxysugar units,
      mostly belonging to the L-hexopyranoside series, comprising generally an
      aminosugar. The different compounds belonging to this family are structurally
      related as they share a common biosynthetic pathway. Although some statements
      concerning structure activity relationships and molecular requirements for
      activity can be made, published data are not adequate for the comparative
      evaluation of potential antitumor efficacy of biosynthetic anthracyclines. This
      family of natural products is therefore still open for pharmacological
      investigation.

PMID- 9756980
TI  - Review of cardiovascular effects of fluoxetine, a selective serotonin reuptake
      inhibitor, compared to tricyclic antidepressants.
AB  - Fluoxetine is an antidepressant drug, a potent and specific inhibitor of
      serotonin reuptake (SSRI). Evidence suggests that being compared with tricyclic
      antidepressants, fluoxetine may cause significantly fewer anticholinergic,
      antihistaminergic and cardiotoxic side effects in the treatment of major
      depressive disorders. Chronic treatment with fluoxetine was not reported to
      affect the electrocardiogram (ECG). There is no clinical evidence of conduction
      delay and very little evidence of orthostatic hypotension. In the overdosed
      patients fewer cardiac symptoms were reported than with tricyclic
      antidepressants. However, dysrhythmia (atrial fibrillation and bradycardia) and
      syncope associated with fluoxetine treatment and overdose were reported. Although
      such reports have not been common, they do raise concerns. Thus we investigated
      the direct cardiovascular effects of the fluoxetine in isolated heart
      preparations and vessels of rats and rabbits. From 10(-6)M to 10(-4)M
      concentrations fluoxetine showed cardiodepressant and vasodilatory effects. These
      effects were similar to those of previously reported on tricyclic compounds. This
      review is a brief summary of possible cardiovascular effects of fluoxetine and
      other new SSRIs antidepressants from the literature based on experience of
      clinical studies and our experiments with fluoxetine on isolated rat and rabbit
      cardiac preparations and vessels. Possible explanations of the lower incidence of
      cardiovascular complications with fluoxetine in humans and cardiodepressant
      effects in vitro are discussed.

PMID- 9756982
TI  - Glial cells potentiate kainate-induced neuronal death in a motoneuron-enriched
      spinal coculture system.
AB  - AMPA/kainate receptor-mediated excitotoxicity is believed to play a pathogenic
      role in amyotrophic lateral sclerosis. To further characterize the mechanisms
      involved in AMPA/kainate receptor-mediated motoneuron injury, we investigated the
      influence of spinal glial cells on kainate-induced motoneuron death in vitro. A
      motoneuron-enriched neuronal population was obtained from embryonic mouse spinal
      cord by metrizamide density centrifugation. This population was cultured either
      on a pre-established glial feeder layer of ventral spinal origin (coculture) or
      in glia-free conditions (monoculture). Glial feeder layers significantly enhanced
      basal survival of neurons, and supported neuronal differentiation as judged by
      neuronal morphology and expression of the motoneuron markers peripherin and SMI
      32. Neuronal vulnerability to kainate was two- to three-fold higher in coculture
      than in monoculture, and increased significantly with time in coculture. The
      effects of glial feeder layers on neuronal basal survival, differentiation and
      kainate vulnerability were not mimicked by conditioned medium from glial cells.
      The increase in neuronal kainate vulnerability with time in coculture was
      associated with a marked rise in the proportion of cocultured neurons possessing
      Ca2+-permeable AMPA/kainate receptors, as determined by kainate-activated Co2+
      uptake. Neurons in monoculture were unstained by kainate-activated Co2+-uptake.
      Neurons were immunoreactive to specific antibodies against the AMPA receptor
      subunits GluR1 and GluR2 both in monoculture and coculture. This study indicates
      that motoneuron differentiation in coculture is associated with increased
      vulnerability to kainate and increased expression of Ca2+-permeable AMPA/kainate
      receptors. In this paradigm glial cells support basal survival and
      differentiation of neurons, but potentiate kainate-induced neuronal death.

PMID- 9756983
TI  - Characterization of cDNAs encoding a new family of tetraspanins from schistosomes
      -the Sj25 family.
AB  - The tetraspanins, also known as members of the transmembrane 4 superfamily
      (TM4SF), comprise an assemblage of surface antigens reported from mammalian and
      other vertebrate cells, from schistosomes, from fruit flies and from
      Caenorhabditis elegans. Tetraspanins are characterized by the presence of four
      hydrophobic domains, which are presumed to be membrane-spanning, and specific
      conserved motifs. A novel cDNA encoding a new tetraspanin, termed TE736
      (tetraspanin 736), was isolated and characterized from the human blood fluke
      Schistosoma japonicum. Nucleotide and deduced amino acid sequences of the cDNA
      revealed that TE736 was similar to the previously characterized Sm23/Sj23/Sh23
      species homologues and to Sj25/TM4 from schistosomes, and to other tetraspanins.
      Comparison of hydropathicity profiles of TE736, Sj25/TM4 and two novel
      tetraspanin-like sequences from S. mansoni showed that they contain four
      potential transmembrane domains like other tetraspanins. Sequence alignments
      showed there are four highly conserved, cysteine residues on the second predicted
      extracellular loop of TE736. A phylogenetic comparison of the relationship of
      approximately 30 tetraspanins from mammals and other groups revealed that TE736,
      Sj25/TM4 and the two sequences from S. mansoni formed an independent family of
      tetraspanins. We have termed these tetraspanins from schistosomes the Sj25
      family. TE736 appeared to be encoded by a single gene and to be expressed in at
      least two life cycle stages of S. japonicum.

PMID- 9756985
TI  - Effects of ZD6169, a KATP channel opener, on bladder hyperactivity and spinal c
      fos expression evoked by bladder irritation in rats.
AB  - Cystometrographic recording and immunocytochemical techniques were used to
      examine the effects of ZD6169, an ATP-sensitive K+-channel opener, and capsaicin,
      an afferent neurotoxin, on urinary bladder hyperactivity and immediate early gene
      expression in the spinal cord induced by acetic acid (0.25%) irritation of the
      bladder. Chemical irritation of the bladder of the rat increased the frequency of
      voiding reflexes by 8 fold and increased c-fos expression in neurons in the
      dorsal commissure (DCM), sacral parasympathetic nucleus (SPN) as well as the
      medial and lateral dorsal horn (MDH, LDH) of L6 and S1 segments of the spinal
      cord. Pretreatment with ZD6169 (30 nM) for 1 h reduced the effect of acetic acid
      on voiding frequency as reflected by an increase in the intercontraction interval
      (ICI, 137+/-48% increase, P<0.05). ZD6169 also decreased the number of Fos
      positive neurons in the L6 spinal cord, in the DCM (62.1+/-7.1% decrease), SPN
      (48.8+/-7%), MDH (50+/-7.3%) and LDH regions (38. 8+/-10.5%). Similar reductions
      were noted in the S1 spinal cord: 65. 1+/-10.8% in DCM, 53.8+/-11% in SPN, 56+/
      10.4% in MDH and 25.3+/-18. 1% in LDH. Capsaicin pretreatment (125 mg/kg, s.c., 4
      days prior to the experiments) also reduced bladder hyperactivity (550% increase
      in ICI) and decreased the numbers of acetic acid-induced Fos positive neurons
      78.8+/-6.3% in DCM, 73+/-7.8% in MDH, 59.2+/-16% in LDH and 45.2+/-17% in SPN of
      L6 segment of the spinal cord. These results suggest that ZD6169 can influence
      bladder hyperactivity by suppressing the firing of capsaicin-sensitive C-fiber
      bladder afferents which are known to modulate the micturition reflex.

PMID- 9756984
TI  - Sequence of the putative alanine racemase operon in Staphylococcus aureus:
      insertional interruption of this operon reduces D-alanine substitution of
      lipoteichoic acid and autolysis.
AB  - A gene cluster comprising the alanine racemase gene alr was identified 5' to the
      sigB operon in Staphylococcus aureus. It is flanked upstream by four ORFs of
      which one shows similarity to the dpj gene of Escherichia coli, and downstream by
      two ORFs of which the last shows similarity to the E. coli pemK gene. Preliminary
      data suggest that the seven ORFs orf1-orf2-orf3-dpj-alr-orf6-pemK may form an
      operon. Disruption of the proposed operon by insertional mutagenesis leads to a
      drastic loss in the d-alanine (d-Ala) substitution of lipoteichoic acid and to
      delayed autolysis, without affecting the d-Ala substitution of the wall teichoic
      acid.

PMID- 9756986
TI  - Adenosine A1 receptor activation inhibits LTP in sympathetic ganglia.
AB  - The effects of adenosine on long-term potentiation of sympathetic ganglia was
      studied in the isolated superior cervical ganglion of the rat, using
      extracellularly recorded compound action potential as an index of synaptic
      transmission. Adenosine in a small concentration (2 microM) blocked the post
      tetanic potentiation without affecting long-term potentiation. Higher
      concentrations blocked both responses with no significant effect on basal
      transmission. The inhibitory effect appears to be due to activation of adenosine
      A1 receptors. This was indicated by results from experiments with the A1 agonist
      N6-cyclopentyladenosine (1 microM) which caused inhibition of the basal
      transmission as well as long-term potentiation and post-tetanic potentiation.
      This inhibition was readily antagonized by 8-phenyltheophylline (1 microM), an A1
      receptor antagonist. A small enhancement of basal transmission was seen on
      treatment with 8-phenyltheophylline. The inhibitory effect of N6
      cyclopentyladenosine on long-term potentiation was totally prevented when the
      Ca2+ concentration in the superfusate was doubled (from 2.2 to 4.4 mM). The
      adenosine A2 receptor agonist 5'-(N-cyclopropyl)-carboxamidoadenosine (1 microM),
      although caused a slight potentiation of basal transmission, had no significant
      effect on the post-tetanic potentiation or long-term potentiation. The adenosine
      transport inhibitors, dipyridamole (2 microM) and S-(4-nitorobenzyl)-6
      thioinosine (2 microM) caused significant inhibition of the basal ganglionic
      transmission without affecting post-tetanic potentiation or long-term
      potentiation. The effect of dipyradimole on basal transmission was not
      antagonized in the presence of 8-phenyltheophylline suggesting a non-specific
      action. The results suggest that exogenous adenosine can inhibit both post
      tetanic potentiation and long-term potentiation in sympathetic ganglia, probably
      by activation of presynaptic A1 receptors. The results also suggest that
      endogenous adenosine, which is probably released in minute amounts, may only
      modulate basal transmission without influencing induction or maintenance of long
      term potentiation in the superior cervical ganglion.

PMID- 9756987
TI  - The region 3' to Calpha1 gene of human IG heavy chain displays a polymorphic
      duplicated sequence and encodes an RNA associated with polysomes.
AB  - A highly spread polymorphism flanking the 3. Calpha1 human IG heavy chain gene
      was identified. This polymorphism allowed the detection of an internal
      duplication within the 3' flanking region of both Calpha1 and Calpha2. This
      region has a regulatory function with four enhancer structures also present at
      the 3' end of the human Calpha2 as well as in that of mouse and rat single Calpha
      genes. The 5682-bp sequence of clone lambdapl8 described here starts 3' of
      Calpha1 and presents three open reading frames; one of them contains part of the
      tandem repeats with the 20-bp consensus described previously that is expressed in
      a poly(A)+ RNA and found in three dbEST clones of the human tonsillar cDNA
      library. Here, we demonstrate that in the CLF1 B lymphoblastoid cell line, this
      transcript is associated with polysomes. We also discuss the possibility of the
      presence of a new regulatory gene that does not encode an immunoglobulin and maps
      in the human IG heavy chain gene cluster.

PMID- 9756988
TI  - The Tat protein of equine infectious anemia virus (EIAV) activates cellular gene
      expression by read-through transcription.
AB  - The Tat protein of equine infectious anemia virus, EIAV, was shown to augment
      viral gene expression, presumably through interaction with the Tat responsive
      element, TAR. Recently, cell-free polyadenylation assays suggested that
      perturbation of the EIAV TAR secondary structure diminished polyadenylation
      efficiency. The present study indicates that the EIAV TAR regulates the
      efficiency of the 3'-end processing of viral RNA also in transfected cells.
      Moreover, our data suggest that the provision of the EIAV Tat protein in trans
      potentiates read-through transcription through the 3' viral long terminal repeat
      (3' LTR), thus suggesting activation of downstream-located cellular genes.

PMID- 9756989
TI  - Effects of neonatal focal cerebral hypoxia-ischemia on sleep-waking pattern, ECoG
      power spectra and locomotor activity in the adult rat.
AB  - The aim of this study was to determine the influence of neonatal focal cerebral
      hypoxia-ischemia (HI) on sleep-waking pattern, electrocorticogram (ECoG) power
      spectra and locomotor activity (LA) in adult Wistar rats. Seven-day old pups were
      subjected to permanent unilateral ligation of the common carotid artery and
      transient hypoxia (8% O2). At 10 weeks of age, the extent of brain damages was
      evaluated by magnetic resonance imaging (MRI) and homogenous injured animals were
      selected before chronic implantation of radiotelemetry device. Using a single
      ECoG recording channel method, waking (W), paradoxical sleep (PS) and slow wave
      sleep (SWS) were continuously recorded for 72 h and they were semi-automatically
      analyzed off-line. We observed that neonatal HI triggers a cascade of events
      leading, in adult rats, to brain dysfunction characterized by an increase in SWS
      (55.0 vs. 40.2% in sham-operated rats, p<0.05) and a marked decrease in W phases
      duration (43.4 vs. 51.5%, p<0.05) while PS was almost suppressed in HI rats (1.6
      vs. 8.3%, p<0.05). In addition, power spectral analysis of ECoG revealed
      significant (p<0.05) alteration in PS power density with a shift of the dominant
      frequency peak (5.0 to 7.5 Hz for HI and sham-operated rats, respectively).
      During the light period, we found that HI induced a pronounced reduction of LA (
      30%, p<0.05). These results indicate that Wistar rats exposed to a neonatal
      unilateral cerebral HI present significant ECoG activity, sleep-waking pattern
      and behavioral disturbances when adults. However, it remains to establish whether
      such alterations can be prevented by neuroprotective agents.

PMID- 9756990
TI  - Cloning of mouse gamma-glutamyl hydrolase in the form of two cDNA variants with
      different 5' ends and encoding alternate leader peptide sequences.
AB  - Mouse-liver gamma-glutamyl hydrolase (GH) is a lysosomal endopeptidase with an
      acid pH optimum that is activated by sulfhydryl compounds and preferentially
      hydrolyzes the most proximal gamma-glutamyl linkage of longer chain
      polyglutamates of folates and their analogues. We describe the cloning of this
      mouse lysosomal cDNA enzyme from liver GH mRNA in the form of two cDNA variants
      (1.295 and 1.268 kb in length) differing 14-fold (Variant I versus Variant II) in
      relative frequency that exhibited 5'-end heterogeneity and encoded alternate
      leader peptides. The 5' UTR in these variants also differs in length by 27
      nucleotides. Otherwise, the ORF and 3' UTR in each case are the same. These cDNAs
      encode a protein in which the deduced amino acid sequence shares 78.9 and 69. 1%
      identity to rat and human GH sequences, respectively. Amino acid sequence
      comparisons among the three species identified three conserved Asn sites and two
      conserved Cys residues that may be sites of glycosylation and sulfhydryl compound
      activation, respectively. Variant I GH mRNA was more abundant than Variant II GH
      mRNA in all mouse tissues examined. Variant I GH mRNA levels were extremely high
      in salivary gland, moderately high in kidney, liver, lung, stomach and uterus,
      low in small intestine, brain and fetal liver and relatively rare in thymus,
      spleen and skeletal muscle. Abundance of GH mRNA among tumors varied from low to
      high, with no discernible correlation with their tissue of origin.

PMID- 9756991
TI  - Lateralized effects of ethanol on aggression and serotonergic systems in Anolis
      carolinensis.
AB  - The lateralized effects of ethanol (ETOH) upon behavior and monoamine
      biochemistry in the lizard, Anolis carolinensis, were examined. Eight adult male
      anoles consumed solutions of 19% ethanol (ETOH) twice daily over the course of 18
      days, while controls consumed water. ETOH decreased the use of the left eye/right
      hemisphere, but not the right eye/left hemisphere, during territorial aggression
      (p<0.05). During crossover (i.e., ETOH to water and vice versa) this effect was
      reversible and replicable. Biochemically, an asymmetry was observed in 5-HT
      levels in the raphe both in ETOH and controls. ETOH increased levels of serotonin
      (5-HT; p<0.05), and 5-HIAA/5-HT ratios (p<0.05) in the raphe; serotonin levels in
      several brain regions correlated with aggressive responses. These results suggest
      that ETOH boosts 5-HT levels in animals subchronically exposed to ETOH. They
      further suggest that asymmetry in endogenous 5-HT systems may account for the
      asymmetrical regulation of aggression generally, and may explain the behavioral
      effects of ETOH upon lateralized aggression.

PMID- 9756992
TI  - Molecular cloning and sequence analysis of a chicken cDNA encoding tyrosinase
      related protein-2/DOPAchrome tautomerase.
AB  - We have cloned and sequenced a chicken cDNA encoding an l-DOPAchrome tautomerase
      (DCT) from an embryonic melanocyte cDNA library. The chicken DCT gene encodes a
      deduced protein of 516 amino acids (aas) and shares 69.2% and 69.9% aa sequence
      identity with the deduced mouse and human DCT proteins, respectively. Northern
      blot hybridisation analysis reveals a DCT transcript of 3.5kb in RNA from the
      retinal pigment epithelium (RPE) of chick embryos. Genomic Southern blot
      hybridisation analysis suggests that the chicken DCT gene consists of several
      introns and spans between 15 and 30kb of the chicken genome. This study completes
      the sequencing of all the members of the chicken tyrosinase-related protein gene
      family and provides evidence that this gene family is conserved between avians
      and mammals.

PMID- 9756993
TI  - Cortical spreading depression activates trophic factor expression in neurons and
      astrocytes and protects against subsequent focal brain ischemia.
AB  - We recently reported that cortical spreading depression (CSD), used to
      precondition rat brain, reduced cortical infarction volume resulting from focal
      cerebral ischemia by middle cerebral artery occlusion (MCAO) 3 days later. The
      mechanisms underlying this protective effect by CSD remains to be explored. In
      this study, we confirm that CSD is neuroprotective when KCl is applied epidurally
      rather than intracortically. Neocortical infarct volume was 101.3+/-48.5 mm3 and
      45.3+/-44.1 mm3 in the sham and CSD group, respectively (p<0.05). Using image
      analysis, we identified the cortical region spared from infarction by the prior
      CSD. We then determined the distribution of brain-derived neurotrophic factor
      (BDNF) and basic fibroblast growth factor (bFGF) mRNA and the time course of
      their expression in groups of animals treated with CSD and their controls. We
      also examined the response of astrocytes to CSD using glial fibrillary acidic
      protein (GFAP) as a marker. In situ hybridization (done at 0, 3, 12, 24, 72 or
      168 h after CSD) showed significant elevation of BDNF mRNA in the cortex
      immediately after CSD in a distribution surrounding the spared cortex, while bFGF
      mRNA rose 12 h after CSD and appeared more within the core of the ischemic
      region. Immunohistochemistry (done at 1, 3 or 7 days after CSD) demonstrated GFAP
      in the neocortex, with a peak at 3 days after CSD. Heat shock protein 72 (HSP72)
      expression was not affected by CSD. We concluded that upregulation of trophic
      factors and activation of glial cells may contribute to the neuroprotection
      induced by CSD.

PMID- 9756994
TI  - Characterization of the chicken interleukin-1beta converting enzyme (caspase-1)
      cDNA and expression of caspase-1 mRNA in the hen.
AB  - We have cloned and sequenced a chicken homolog to the mammalian interleukin-1beta
      (IL-1beta)-converting enzyme (caspase-1) cDNA and have evaluated caspase-1 mRNA
      expression in various tissues from the domestic hen, including ovarian follicle
      granulosa and theca layers. The deduced amino acid (aa) sequence of chicken
      caspase-1 is 44.9% identical to human caspase-1, and contains an active site
      pentapeptide that is characteristic of the caspase family of cysteine proteases.
      Of interest, however, is that the putative chicken caspase-1 cDNA is predicted to
      encode a comparatively short (19aa) N-terminal prodomain, as well as two Cys
      residues within the active pentapeptide (QC162C163RG) as compared to the QACRG
      pentapeptide found in the mammalian caspase-1 sequence. While the chicken caspase
      1 mRNA transcript is widely expressed among different tissues, levels are
      particularly high in the bursa of Fabricius and comparatively low in ovarian
      follicles at all stages of development. Finally, treatment of granulosa cells
      with IL-1beta, the primary if not sole product of caspase-1 activity, fails to
      either promote apoptotic cell death or enhance viability in granulosa cells.
      Considering the relatively low levels of caspase-1 mRNA expression in ovarian
      follicle tissues plus the inability of IL-1beta to alter granulosa cell
      viability, in vitro, it is concluded that caspase-1 is not an integral part of
      the apoptotic pathway in granulosa cells. However, the pattern of mRNA expression
      is consistent with a requirement for caspase-1 mediated IL-1beta production in
      chicken immune tissues.

PMID- 9756995
TI  - Inhibition of spontaneous inhibitory postsynaptic currents (IPSC) by
      noradrenaline in rat supraoptic neurons through presynaptic alpha2-adrenoceptors.
AB  - It has been shown that noradrenergic activation has great influence on the
      activities of hypothalamic supraoptic neurons. No direct evidence has been
      reported on the presynaptic effects of adrenoceptors in the actions of
      noradrenaline on supraoptic neurons, although postsynaptic mechanisms have been
      studied extensively. In the present study, we explored presynaptic effects of
      noradrenaline on the supraoptic neurons by measuring spontaneous inhibitory
      postsynaptic currents (IPSC) with the whole-cell patch-clamp technique.
      Noradrenaline reduced the frequency of IPSCs in a dose-dependent (10(-9) to 10(
      3) M) and reversible manner. Noradrenaline did not affect the amplitude of IPSCs
      at concentrations of 10(-9) to 10(-5) M, but reduced the amplitude of IPSCs at
      high concentrations (10(-4) and 10(-3) M). The inhibitory effects of
      noradrenaline were mimicked by the alpha2-agonist clonidine (10(-4) M), but not
      by the alpha1-agonist methoxamine (10(-4) M) nor by the beta-agonist
      isoproterenol (10(-4) M). Moreover, the inhibitory effects of noradrenaline on
      IPSCs were blocked by the non-selective alpha antagonist phentolamine (10(-4) M)
      or the selective alpha2-antagonist yohimbine (10(-4) M), but not by the alpha1
      antagonist prazosin (10(-4) M). These results suggest that noradrena-line
      inhibits release of GABA from the presynaptic GABAergic terminals of the
      supraoptic neurons by activating presynaptic alpha2-adrenoceptors and such
      presynaptic mechanisms may play a role in the excitatory control of SON neurons
      by noradrenergic neurons.

PMID- 9756997
TI  - A procedure for cloning genomic DNA fragments with increasing thermoresistance.
AB  - Genomic DNAs have been cleaved by restriction or sonication, and the resulting
      double-stranded fragments have been exposed to increasing temperatures. This
      treatment may induce the helix-coil transition either in a single or in several
      steps, depending on the size and composition of the duplexes. Eventually, a
      critical temperature is reached at which each duplex melts completely and the two
      constitutive single strands separate. A transition interval can thus be defined
      for each duplex by the temperature at which the earliest strand separation takes
      place and that at which the most resistant double-stranded core collapses. If
      solutions containing a mixture of DNA duplexes are exposed to temperatures within
      their transition intervals, three kinds of molecules should originate: (1)
      duplexes that have not yet initiated the melting phase; (2) duplexes that have
      undergone only partial melting; and (3) single strands that derive from fully
      melted duplexes. If the heated solutions are quickly cooled to 0 degreesC, only
      the molecules from the first two classes can be ligated to a compatibly ended
      vector and cloned: class (1) are intact duplexes, and class (2) are molecules
      that snap immediately back to fully duplex structures: both are double-stranded.
      Conversely, the single strands of class (3) may not reanneal and thus be neither
      ligated nor cloned. We have tested the procedure on restricted coliphage lambda
      DNA, in view of its compartmentalized organization and known sequence. Then, we
      have applied it to human genomic DNA fragmented by sonication. After cloning of
      the available duplexes in a bacterial plasmid, libraries of molecules endowed
      with a progressively higher thermoresistance can be prepared for thermodynamic
      and genomic studies.

PMID- 9756996
TI  - Molecular events after antisense inhibition of hMSH2 in a HeLa cell line.
AB  - To establish a cause-effect relationship between the human mismatch repair
      pathway deficiency and the observed phenotypes, a hMSH2 deficient HeLa cell line
      (HeLa-MSH2-) was established by transfecting the HeLa cells with an antisense RNA
      expression plasmid. The expression plasmid was constructed by inserting an 851 bp
      fragment of hMSH2 cDNA into the polyclonal site of the vector pREP9 in a reversed
      orientation. The production of the mismatch binding protein, hMSH2, was inhibited
      in HeLa-MSH2- cells, as demonstrated by Western blotting and band shift assay of
      its whole cell extract. The growth rate of this cell line was not different from
      the parental HeLa cells soon after transfection. However, the rate was faster
      after 10 subcultures. The spontaneous mutation frequency at the hypoxanthine
      phosphoribosyltransferase (HPRT) locus increased markedly, but no N-methyl-N'
      nitro-N-nitrosoguanidine (MNNG) tolerance appeared in this cell line. Our results
      clearly demonstrated several molecular events happened after the inhibition of a
      major mismatch recognition protein, hMSH2, in the mismatch repair pathway,
      mimicking carcinogenesis processes.

PMID- 9756998
TI  - Regulation of cytosol-nucleus pH gradients by K+/H+ exchange mechanism in the
      nuclear envelope of neonatal rat astrocytes.
AB  - In order to study the subcellular heterogeneity of intracellular H+ concentration
      in reactive astrocytes, the pH in the nucleus and cytosol of cultured astrocytes
      was measured using a confocal laser scanning microscope (CLSM) and pH indicator
      dye, 5'(and 6')-carboxyseminaphthofluorescein (carboxy SNAFL-1). The change in
      intracellular pH was indexed by the fluorescence ratio (F535/F610) at an
      excitation wavelength of 514.5 nm. The in vitro fluorescence ratio increased as
      pH decreased. This ratio in the nucleus was significantly lower than that in the
      cytosol of astrocytes when perfused by HEPES-buffered Hanks' balanced salt
      solution (HHBSS) at pH 7.4. Acid stimulations of cells (pH 5.0) raised the
      fluorescence ratio in both nucleus and cytosol. However, the increase in the
      fluorescence ratio of the nucleus was less than that of cytosol. Treatment with a
      K+/H+ ionophore, nigericin (20 microM), reversibly nullified this cytosol-nucleus
      pH gradient. These findings suggest that a buffering mechanism(s) for maintaining
      of intracellular pH exists between the nucleus and cytosol, and a K+/H+ exchanger
      may act on the nuclear envelope to eventuate intranuclear pH maintenance in the
      living cells.

PMID- 9756999
TI  - Comparative studies on genotoxicity and antigenotoxicity of natural and synthetic
      beta-carotene stereoisomers.
AB  - To evaluate the practical value of natural beta-carotene (NbetaC) and to
      elucidate the apparent discrepancy between epidemiological observations and
      intervention trials on the role of beta-carotene (betaC) in tumor prevention, the
      genotoxicity and the antigenotoxicity of NbetaC and synthetic betaC crystal
      (SbetaCC) stereoisomers were studied comparatively using chromosome aberration
      analysis and the micronucleus test in human lymphocytes in vitro. NbetaC was
      extracted from the halotolerant algae Dunaliella salina. The NbetaC crystal
      (NbetaCC) preparation is about 70% all-trans (TbetaC) and 8% 9-cis (CbetaC). The
      NbetaC oil (NbetaCO) preparation is about 40% all-trans and 38% 9-cis. SbetaCC is
      more than 97% all-trans, and the 9-cis can not be detected. The mixture of betaC
      (betaCM) preparation is 74% SbetaCC and 26% NbetaC. Our results show no
      genotoxicity of 1-30 microg/ml NbetaCC, but this concentration of NbetaCC
      inhibited significantly gamma-ray-induced micronucleus formation in human
      lymphocytes in vitro. One to thirty microg/ml NbetaCO was most effective against
      both gamma-ray-induced and spontaneous micronucleus formation. However, no
      influence of NbetaCO on spontaneous chromosome aberrations in human lymphocytes
      in vitro was observed. NbetaCO suppressed significantly mitomycin C (MMC)-induced
      chromosome aberrations. One to thirty microg/ml SbetaCC induced a dose-dependent
      increase in micronucleus frequency, and also inhibited gamma-ray-induced
      micronucleus formation. No effect of betaCM on spontaneous chromosome aberrations
      was found. One to thirty microg/ml betaCM is more effective against MMC-induced
      chromosome aberrations than NbetaCO. These results suggest that CbetaC might play
      a critical role in the genotoxicity and antigenotoxicity of SbetaCC and NbetaC.
      The genotoxic activity of SbetaCC might be involved in carcinogenesis. NbetaC or
      betaCM could be of practical value in tumor prevention and supplementary
      treatment.

PMID- 9757000
TI  - Establishing the Cryptosporidium parvum karyotype by NotI and SfiI restriction
      analysis and Southern hybridization.
AB  - The molecular karyotype of the coccidian parasite Cryptosporidium parvum has
      proven difficult to study because chromosomes of similar sizes migrate together
      when submitted to pulsed-field gel electrophoresis (PFGE). In the present work,
      the karyotype was studied by restriction of chromosome-sized DNA with the rare
      cutting enzymes NotI and SfiI, followed by PFGE separation of the restriction
      fragments and Southern hybridization. These experiments showed that the C. parvum
      karyotype is formed by eight chromosomes, ranging in size from approximately 0.95
      to 1.45 million base pairs (Mbp), accounting for a genome size of 9.6Mbp. As a
      first step towards the construction of a physical map of the C. parvum genome, a
      total of 20 probes, including 16 genes and the ribosomal DNA (rDNA) sequence, was
      mapped to intact chromosomes and to their restriction fragments. In this way, all
      chromosomes, but one, were identified by specific markers. A comparison of
      mapping data of homologous genes from different species belonging to the phylum
      Apicomplexa showed differences in the distribution of rDNA sequences and in the
      chromosomal localization of alpha- and beta-tubulin genes. The variation in
      genome size among these parasites is also discussed.

PMID- 9757001
TI  - Role of the subthalamo-nigral input in the control of amygdala-kindled seizures
      in the rat.
AB  - The substantia nigra pars reticulata (SNpr) is a critical site for the control of
      epileptic seizures. Potentiation of the inhibitory GABAergic input from the
      striatum to the SNpr suppresses primary or secondary generalized seizures in the
      rat. The purpose of this study was to examine the possible involvement of the
      excitatory glutamatergic input from the subthalamic nucleus to the SNpr in the
      control of both the electroencephalographic and the motor components of amygdala
      kindled seizures in the rat. Microinjections of either an N-methyl-D-aspartate
      (NMDA) antagonist in the substantia nigra or a GABAA agonist in the subthalamic
      nucleus, significantly reduced motor seizures but did not modified the
      afterdischarges. These results provide evidence for the involvement of the
      subthalamo-nigral projection in the modulation and the propagation of the motor
      components of amygdala-kindled seizures.

PMID- 9757002
TI  - Biomonitoring of workers exposed to lead. Genotoxic effects, its modulation by
      polyvitamin treatment and evaluation of the induced radioresistance.
AB  - A population monitoring study was performed, by using the micronucleus (MN) assay
      in human peripheral lymphocytes, to investigate whether occupational exposure to
      lead is genotoxic to workers. In addition to the exposed workers group, two more
      groups were studied, an external group from a factory without exposure to lead
      and an internal control group, from the same factory as the exposed workers, but
      that were not directly exposed to lead. Measures of lead levels at working place
      and in blood were calculated, and blood samples were collected to carry out a MN
      study. The results from these studies indicate that the blood from workers
      directly exposed contained high levels of lead, compared with the other groups,
      and a significant increase in the frequency of both the total number of MN and
      the number of binucleated cells carrying MN appeared. In addition, a study on the
      antimutagenic effects of a polyvitamin rich diet was conducted by measuring the
      frequency of MN after the workers had a four month daily intake of a polyvitamin
      polymineral complex. These results clearly show a significant reduction of the MN
      frequency evaluated after this treatment, obtaining values that were even lower
      than those obtained in the internal control group. Finally, a challenge assay was
      carried out to determine response to gamma-radiation as indication of any kind of
      radiosensitivity or radioresistance. The results of this experiment did not show
      any significant variation in the increase of the frequency of MN after challenge
      irradiation in the lead exposed workers; nevertheless this increase was
      significantly reduced in the sample obtained after the polyvitamin treatment
      indicating a radioresistance response.

PMID- 9757003
TI  - Identification of the start sites for the 1.9- and 1.4-kb rat transforming growth
      factor-beta1 transcripts and their effect on translational efficiency.
AB  - Three distinct transforming growth factor-beta1 (TGF-beta1) transcripts of 2.5,
      1.9 and 1.4kb have been described, but the start sites and functional
      significance of the shorter transcripts are unknown. Here, we have cloned and
      sequenced a rat genomic fragment encoding approximately 1250 bases upstream of
      the start of the TGF-beta1 open reading frame. Using a combination of
      ribonuclease protection and 5' RACE-PCR analysis, we have mapped the start sites
      for the two shorter TGF-beta1 transcripts in NRP152 cells, a rat prostatic
      epithelial cell line that expresses all three transcripts at high levels. The 1.4
      kb mRNA starts 25 bases upstream of the initiator AUG, whereas the 1.9-kb mRNA
      has two start sites 366 and 401 bases upstream of the AUG. Polysome analysis of
      the NRP152 cells indicates that the 1.9-kb transcript is very efficiently
      translated, whereas the 2.5- and 1.4-kb transcripts appear to be poorly
      translated. Differential regulation of TGF-beta1 transcript size may therefore
      represent an important mechanism for regulating TGF-beta1 protein levels.

PMID- 9757004
TI  - Progesterone withdrawal I: pro-convulsant effects.
AB  - Pro-convulsant withdrawal properties have been reported for a variety of GABA
      modulatory drugs, such as the benzodiazepines (BDZs, [S.E. File, The history of
      BDZ dependence: a review of animal studies, Neurosci. Biobehav. Rev. 14 (1990)
      135-146; P.R. Finley, P. E. Nolan, Precipitation of BDZ withdrawal following
      sudden discontinuation of midazolam, DICP 23 (1989) 151-152]), barbiturates and
      ethanol [N. Kokka, D.E. Sapp, U. Witte, R.W. Olsen, Sex differences in
      sensitivity to pentylenetetrazol but not in GABAA receptor binding, Pharm.
      Biochem. Behav. 43 (1992) 441-447]. In this report, we test the hypothesis that
      pro-convulsant effects are produced by withdrawal from the GABA-modulatory
      neurosteroid 3alpha-OH-5alpha-pregnan-20-one (3alpha,5alpha-THP) after sustained
      exposure to elevated circulating levels of its parent compound progesterone (P).
      Seizure activity was precipitated by picrotoxin or with the BDZ inverse agonist n
      methyl-beta-carboline-3-carboxamide (beta-CC), and a seizure rating determined 24
      h after abrupt discontinuation of P following a multiple withdrawal/chronic
      administration paradigm. In some cases, a pseudopregnant rat model was employed
      to produce increased ovarian production of P prior to withdrawal (ovariectomy).
      Rats undergoing P withdrawal exhibited greater seizure-like activity than vehicle
      treated controls, and received seizure scores in the same range as rats
      undergoing BDZ withdrawal. Administration of a 5alpha-reductase blocker, MK-906,
      along with P, prevented this pro-convulsant effect of P withdrawal, suggesting
      that the GABA-modulatory 3alpha,5alpha-THP is the active compound responsible for
      this withdrawal effect. Combined administration of P and diazepam produced
      synergistic effects upon withdrawal and produced a seizure score higher than
      observed after withdrawal from either agent alone. These results suggest that P
      exhibits withdrawal properties via the neuroactive steroid 3alpha, 5alpha-THP,
      that include exacerbation of seizure activity. These results may have clinical
      relevance, as increased incidence and severity of seizures has been reported in
      susceptible women during times of declining circulating levels of P across the
      menstrual cycle [T. Backstrom, B. Zetterlund, S. Blom, M. Romano, Effects of
      intravenous progesterone infusions on the epileptic discharge frequency in women
      with partial epilepsy, Acta Neurol. Scand. 69 (1984) 240-248; A.G. Herzog,
      Progesterone therapy in women with complex partial and secondary generalized
      seizures, Neurology 45 (1995) 1660-1662].

PMID- 9757006
TI  - Progesterone withdrawal. II: insensitivity to the sedative effects of a
      benzodiazepine.
AB  - Previous results from this lab have demonstrated that the GABA-modulatory steroid
      3alpha-OH-5alpha-pregnan-20-one (3alpha, 5alpha-THP) exhibits withdrawal
      properties, increasing anxiety [M.A. Gallo, S.S. Smith, Progesterone withdrawal
      decreases latency to and increases duration of electrified prod burial: a
      possible rat model of PMS anxiety, Pharmacol. Biochem. 46 (1993) 897-904.] and
      seizure susceptibility [S.S. Smith, Q.H. Gong, F.-C. Hsu, R.S. Markowitz, J. M.H.
      ffrench-Mullen, X. Li, GABAA receptor alpha4 subunit suppression prevents
      withdrawal properties of an endogenous steroid, Nature 392 (1998) 926-930.] upon
      abrupt discontinuation after chronic administration of its parent compound,
      progesterone (P), in a manner similar to other GABA-modulatory drugs. Further, we
      have demonstrated that withdrawal from P produces insensitivity to the
      potentiating effects of the benzodiazepine (BDZ) lorazepam (LZM) on GABA-gated Cl
      current [A.-M.N. Costa, K.T. Spence, S.S. Smith, J.M. H. ffrench-Mullen,
      Withdrawal from the endogenous steroid progesterone results in GABAA currents
      insensitive to BDZ modulation in rats CA1 hippocampus, J. Neurophysiology 74
      (1995) 464-469; S.S. Smith, Q.H. Gong, F.-C. Hsu, R.S. Markowitz, J.M.H. ffrench
      Mullen, X. Li, GABAA receptor alpha4 subunit suppression prevents withdrawal
      properties of an endogenous steroid, Nature 392 (1998) 926-930.], assessed using
      whole cell patch clamp procedures on pyramidal neurons acutely dissociated from
      CA1 hippocampus. The purpose of the present study was to examine the withdrawal
      effects of P on the sedative potency of LZM, tested behaviorally as the ability
      to maintain position on a variable speed treadmill following LZM administration
      (0.75 mg/kg). Both continuous (continuous release P capsule, single withdrawal)
      as well as discontinuous (multiple P injection, multiple withdrawal) paradigms
      were tested. Longer continuous release paradigms were more effective in
      abolishing the sedative effects of LZM, without producing a change in baseline
      response. The LZM insensitivity observed following the multiple withdrawal
      paradigm was prevented by prior intraventricular administration of antisense
      oligonucleotide against the alpha4 subunit of the GABAA receptor. These results
      support the hypothesis that withdrawal from P decreases the behavioral response
      to LZM as a direct result of increases in the alpha4 subunit of the GABAA
      receptor. Withdrawal from P occurs endogenously during pre-menstrual and post
      partum periods, when decreased response to BDZ has been reported.

PMID- 9757005
TI  - Blue/white screening of recombinant plasmids in Gram-positive bacteria by
      interruption of alkaline phosphatase gene (phoZ) expression.
AB  - The process of screening bacterial transformants for recombinant plasmids is made
      more rapid and simple by the use of vectors with visually detectable reporter
      genes. In such systems, an alteration in colony phenotype occurs when a vector
      borne indicator gene is interrupted with exogenous DNA. Although the lacZ system
      has been used extensively for this purpose in E. coli, analogous systems for use
      in Gram-positive bacteria remain uncommon. We have developed a Gram-positive
      cloning vector that utilizes the interruption of an alkaline phosphatase gene,
      phoZ, to identify recombinant plasmids. To facilitate introduction of foreign
      DNA, a multiple cloning site (MCS) was inserted distal to the region coding for
      the putative signal peptide of phoZ. Alkaline phosphatase expressed from the
      derivative phoZ gene (phoZMCS) retained activity similar to that of the native
      protein. The phoZMCS was transferred to pJS3, a well-characterized, high-copy
      number, and broad-host-range plasmid, to produce pDC123. In pDC123, phoZMCS was
      transcriptionally linked to the chloramphenicol acetyl transferase (cat) gene
      under the control of the constitutively expressed tetM and cat promoters that
      drive cat expression in pJS3. S. agalactiae (Group B streptococci, GBS), E.
      faecalis, S. pyogenes, S. gordonii, and E. coli containing pDC123 displayed a
      blue colonial phenotype on agar containing 5-bromo-4-chloro-3-indolyl phosphate
      (X-p), which was readily distinguished from that of colonies containing the
      parent plasmid pJS3. Introduction of foreign DNA into the MCS of phoZMCS produced
      a white colonial phenotype in E. coli and GBS on agar containing X-p and allowed
      discrimination between transformants containing recombinant plasmids versus those
      maintaining self-annealed or uncut vector. We have used pDC123 to subclone the
      cpsE gene from the plasmid pCER111, which carries a 9.0-kb fragment of the GBS
      capsular polysaccharide synthesis locus. The plasmid pDC123 containing cpsE was
      isolated by direct electroporation into GBS strain A909 with selection of
      transformants containing recombinant plasmids achieved by 'blue/white' screening,
      without the use of an intermediate host. This new cloning vector should improve
      the efficiency of performing recombinant DNA experiments in Gram-positive
      bacteria.

PMID- 9757007
TI  - Use of alkaline comet assay (single cell gel electrophoresis technique) to detect
      DNA damages in lymphocytes of operating room personnel occupationally exposed to
      anaesthetic gases.
AB  - Here, we report the possible in vivo induction DNA damage by exposure to various
      waste anaesthetic gases such as halothane, nitrous oxide and isoflurane. The
      alkaline comet assay (single cell gel electrophoresis technique) was carried out
      on 66 operating room personnel (anaesthetists [doctors]; anaesthesia nurses and
      anaesthesia unit technicians) currently employed at the Ankara Hospital in
      Turkey. A significant increase in the number of lymphocytes with DNA migration
      was observed in operating room personnel as compared to controls. Also, the
      extent of damage in exposed smokers were significantly higher than exposed
      nonsmokers. This study supports the existence of an association between DNA
      damage and occupational exposure to inhalation anaesthetics.

PMID- 9757008
TI  - Micronucleus formation in human amnion cells after exposure to 50 Hz MF applied
      horizontally and vertically.
AB  - Micronucleus (MN) induction as a genotoxic effect of extremely-low-frequency
      electromagnetic fields (ELF-EMF, 50 Hz, 1 mT) was studied in human amniotic fluid
      cells (AFC) after continuous exposure to magnetic fields (MF), oriented
      horizontally and vertically with respect to the surface of the culture medium, at
      different time points. To compare the effectiveness of different exposure
      systems, a Helmholtz-coil system and a so-called Merritt-coil system was used. A
      statistically significant increase in MN frequency could be detected in exposed
      cells compared to controls after 72 h continuous exposure to MF applied
      vertically in the Merritt-coil system, while no effect was found after exposure
      in the Helmholtz-coil system. Furthermore, a significant increase in MN induction
      occurred after 24, 48 and 72 h exposure to MF applied horizontally in the
      Helmholtz-coil system in comparison to controls, whereas horizontally MF
      generated in the Merritt-coil system induced no genotoxic effects. To exclude
      suppression of indirect EMF-induced DNA-lesions, we studied MN formation in the
      presence of N-Acetyl-p-aminophenol (APAP, Paracetamol(R)), which is an inhibitor
      of DNA-repair mechanisms. We found a dose-dependent increase of MN formation in
      APAP-treated AFC cells, but no significant further increase in MN frequency after
      additional MF exposure. Therefore we conclude, that EMF-induced MN formation is
      not caused by directly or indirectly induced clastogenic mechanisms. The obtained
      results show that the orientation of MF with respect to the cell culture dish and
      the physical condition of the exposure system is of major importance for the
      induction of micronuclei in certain cell types. Therefore, the reason for
      inconsistent results published in the literature may be caused by the variability
      of exposure systems, the exposure conditions and the cell types used.

PMID- 9757009
TI  - Isolation, characterisation and embryonic expression of WNT11, a gene which maps
      to 11q13.5 and has possible roles in the development of skeleton, kidney and
      lung.
AB  - The Wnt gene family encodes a set of signalling molecules, thought to play an
      important role in key processes of embryonic development. In vertebrates as a
      whole 20 different Wnt genes have been identified to date, however, a complement
      of only 16 have been identified in man and for some of these the complete coding
      sequences are unavailable. We have recently isolated the full-length cDNA
      sequence of a new human WNT gene, WNT11, investigated its genomic organisation
      and performed detailed expression studies in early human embryos. These have
      shown that the expression of human WNT11 is restricted to the perichondrium of
      the developing skeleton, lung mesenchyme, the tips of the ureteric buds and other
      areas of the urogenital system and the cortex of the adrenal gland. This, for the
      first time, provides information for the embryonic expression of human WNT11. We
      have mapped WNT11 to 11q13.5 and this together with its expression in the
      perichondrium of the developing skeleton, makes it a plausible candidate gene for
      HBM, which has been previously linked to markers from this region.

PMID- 9757010
TI  - Maternal exposure to delta9-tetrahydrocannabinol facilitates morphine self
      administration behavior and changes regional binding to central mu opioid
      receptors in adult offspring female rats.
AB  - Opiates and cannabinoids are among the most widely consumed habit-forming drugs
      in humans. Several studies have demonstrated the existence of interactions
      between both kind of drugs in a variety of effects and experimental models. The
      present study has been focused to determine whether perinatal delta9
      tetrahydrocannabinol (Delta9-THC) exposure affects the susceptibility to
      reinforcing effects of morphine in adulthood and whether these potential changes
      were accompanied by variations in mu opioid receptor binding in brain regions
      related to drug reinforcement. Adult female rats born from mothers that were
      daily treated with delta9-THC during gestation and lactation periods, exhibited a
      statistically significant increase in the rate of acquisition of intravenous
      morphine self-administration behavior when compared with females born from
      vehicle-exposed mothers, an effect that did not exist in delta9-THC-exposed male
      offspring. This increase was significantly greater on the last day of acquisition
      period. There were not significant differences when the subjects were lever
      pressing for food. In parallel, we have also examined the density of mu opioid
      receptors in the brain of adult male and female offspring that were exposed to
      Delta9-THC during the perinatal period. Collectively, perinatal exposure to
      delta9-THC produced changes in mu opioid receptor binding that differed
      regionally and that were mostly different as a function of sex. Thus, delta9-THC
      exposed males exhibited a lower density for these receptors than their respective
      oil-exposed controls in the caudate-putamen area as well as in the amygdala
      (posteromedial cortical nucleus). On the contrary, delta9-THC-exposed females
      exhibited higher density of these receptors than their respective oil-exposed
      controls in the prefrontal cortex, the hippocampus (CA3 area), the amygdala
      (posteromedial cortical nucleus), the ventral tegmental area and the
      periaqueductal grey matter, whereas the binding was lower than control females
      only in the lateral amygdala. These results support the notion that perinatal
      delta9-THC exposure alters the susceptibility to morphine reinforcing effects in
      adult female offspring, in parallel with changes in mu opioid receptor binding in
      several brain regions.

PMID- 9757011
TI  - Alzheimer's beta-amyloid peptides induce inflammatory cascade in human vascular
      cells: the roles of cytokines and CD40.
AB  - Accumulating evidence suggests that beta-amyloid (Abeta)-induced inflammatory
      reactions may partially drive the pathogenesis of Alzheimer's disease (AD).
      Recent data also implicate similar inflammatory processes in cerebral amyloid
      angiopathy (CAA). To evaluate the roles of Abeta in the inflammatory processes in
      vascular tissues, we have tested the ability of Abeta to trigger inflammatory
      responses in cultured human vascular cells. We found that stimulation with Abeta
      dose-dependently increased the expression of CD40, and secretion of interferon
      gamma (IFN-gamma) and interleukin-1beta (IL-1beta) in endothelial cells. Abeta
      also induced expression of IFN-gamma receptor (IFN-gammaR) both in endothelial
      and smooth muscle cells. Characterization of the Abeta-induced inflammatory
      responses in the vascular cells showed that the ligation of CD40 further
      increased cytokine production and/or the expression of IFN-gammaR. Moreover, IL
      1beta and IFN-gamma synergistically increased the Abeta-induced expression of
      CD40 and IFN-gammaR. We have recently found that Abeta induces expression of
      adhesion molecules, and that cytokine production and interaction of CD40-CD40
      ligand (CD40L) further increase the Abeta-induced expression of adhesion
      molecules in these same cells. These results suggest that Abeta can function as
      an inflammatory stimulator to activate vascular cells and induces an auto
      amplified inflammatory molecular cascade, through interactions among adhesion
      molecules, CD40-CD40L and cytokines. Additionally, Abeta1-42, the more pathologic
      form of Abeta, induces much stronger effects in endothelial cells than in smooth
      muscle cells, while the reverse is true for Abeta1-40. Collectively, these
      findings support the hypothesis that the Abeta-induced inflammatory responses in
      vascular cells may play a significant role in the pathogenesis of CAA and AD.

PMID- 9757012
TI  - An avian cDNA encoding a tyrosine-phosphorylated protein with PDZ, coiled-coil,
      and SAM domains.
AB  - Tyrosine phosphoproteins of size 115-120 kDa were purified from membranes of
      chicken embryo fibroblasts (CEF) infected with Rous sarcoma virus (RSV). A mouse
      was immunized with these proteins, and the immune serum was used to screen a CEF
      cDNA expression library. A highly immunoreactive clone (KS5) was identified and
      characterized. The cDNA of this clone is 2.3 kb in length with a short 5' UTR and
      a single major open reading frame (ORF) encoding a polypeptide of 719 amino
      acids, with a calculated molecular weight of 81.1 kDa. The encoded protein
      contains an amino terminal PDZ domain, followed by a predicted coiled-coil
      region, a PEST domain, and a carboxy-terminal SAM domain. Consensus sequence
      motifs for tyrosine phosphorylation are also present, as are consensus sequences
      for the binding of SH2 and PDZ domains. Antisera from mice immunized with
      bacterially expressed fragments of the KS5 protein recognized proteins of size
      230, 116, and 65 kDa in CEF. In other chicken embryo tissues, a 116-kDa species
      was the predominant protein recognized. The 116-kDa species is tyrosine
      phosphorylated in RSV-CEF. The presence of PDZ and SAM domains in the KS5 protein
      suggests that it may act as a molecular adaptor, promoting and relaying
      information in a signal transduction pathway. It is a member of a family of
      related proteins, all of which have a highly conserved PDZ domain adjacent to a
      coiled-coil region. Two other members of this family are the neuronal proteins
      spinophilin (Allen, P.B., Ouimet, C.C., Greengard, P., 1997. Spinophilin, a novel
      protein phosphatase 1 binding protein localized to dendritic spines. Proc. Natl.
      Acad. Sci. USA 94, 9956-9961) and neurabin (Nakanishi, H., Obaishi, H., Satoh,
      A., Wada, M., Mandai, K., Satoh, K., Nishioka, H., Matsuura, Y., Mizoguchi, A. ,
      Takai, Y., 1997. Neurabin: A novel neural tissue-specific actin filament-binding
      protein involved in neurite formation. J. Cell Biol. 139, 951-961).

PMID- 9757013
TI  - Genotoxicity testing of wastewater sludge using the Allium cepa anaphase
      telophase chromosome aberration assay.
AB  - Wastewater sludges were analysed in the Allium cepa genotoxicity test. They were
      sampled during three winter periods from three Danish municipal wastewater
      treatment plants differing in size and industrial load. The toxicity of the
      sludge was tested in the Allium root inhibition assay, and the results expressed
      as EC30 and EC50 values showed that the toxicity could be positive correlated to
      the industrial load. However, when genotoxicity was tested at concentrations
      corresponding to the EC30 and EC50 values in the A. cepa anaphase-telophase
      assay, only two sludge samples from the smallest plant with the lowest industrial
      load induced significant chromosome aberrations. Concentrations of the heavy
      metal's Pb, Ni, Cr, Zn, Cu, and Cd were also determined and could partly be
      correlated with the toxicity of the sludge and the industrial load of the
      treatment plants.

PMID- 9757014
TI  - Mechanisms of ischemia-induced taurine release in mouse hippocampal slices.
AB  - Taurine release in the hippocampus is markedly potentiated in various cell
      damaging conditions, including ischemia and excitotoxic damage produced by
      glutamate. The increase in the levels of taurine may provide an important
      protective mechanism against excitotoxicity. The mechanisms of the enhanced
      release were now studied in mouse hippocampal slices using a superfusion system.
      The basal release of [3H]taurine was significantly increased in Na+-deficient
      media in normal conditions, whereas the ischemia-evoked release was decreased,
      indicating the participation of Na+-dependent transport processes. The
      involvement of taurine transport carriers in the release was confirmed with the
      structural analogs, hypotaurine and beta-alanine. These amino acids potentiated
      the release by trans-stimulation in normoxia. In Na+-free conditions, this
      heteroexchange was not discernible, the carriers not being functional without
      Na+. In ischemia, the marked potentiation of taurine release by hypotaurine and
      beta-alanine further indicates that the Na+-requiring transporters also operate
      in ischemia. The effects of membrane disruption on taurine release due to
      activation of phospholipases were estimated using phospholipase and protein
      kinase inhibitors, which had no marked effects on hippocampal taurine release.
      The chloride channel blockers, 4-acetamido-4'-isothiocyanostilbene-2, 2'
      disulphonate (SITS) and diisothiocyanostilbene-2,2'-disulphonate (DIDS), reduced
      the ischemia-induced release, suggesting that taurine diffusion through an anion
      channel is partially responsible for the enhanced release in ischemia.

PMID- 9757015
TI  - Genotoxicity tests for new chemicals in Germany: routine in vitro test systems.
AB  - According to regulations in the European Union, new chemical substances must be
      notified before they can be introduced onto the market. One of the prerequisites
      for notification is that toxicological properties, including mutagenicity, are
      examined. In this paper, a report on routine in vitro mutagenicity testing is
      given for 776 new substances notified in Germany between 1982 and 1997. In
      general, the methodological quality of testing was in line with internationally
      accepted guidelines. Bacterial gene mutation tests (Bact) were conducted for
      nearly all of the substances, 13.4% were positive. Of the Bact-positive
      substances, 36 were also tested in the in vitro chromosomal aberration test
      (CAbvit) and the mammalian cell gene mutation test (MCGM). Twenty-six of these
      (72. 2%) were negative in both mammalian cell tests indicating that the genotoxic
      potentials of the substances are not relevant for man. Of all new substances, 333
      were tested in CAbvit, here the percentage of positive findings was 25.2%. More
      than 80% of the in vitro clastogens were negative in the Bact. With respect to a
      sensitive detection of genotoxic potentials of substances, the combination
      'Bact+CAbvit' is appropriate for basic testing. In our database CHL cells were
      more sensitive to clastogenic effects than other cell types. Only very few
      clastogens were identified as 'high toxicity clastogens'. MCGM tests were
      performed for 118 substances, quite often as follow-up in case of positive Bact
      tests. In total, 12.7% of the substances were positive in the MCGM. However,
      there was a clear difference in the frequencies of positive findings in HPRT
      tests (5.5%) and mouse lymphoma assays (MLA; 37.0%). None of the MCGM-positive
      substances was a 'unique positive', i.e., negative in Bact and CAbvit.

PMID- 9757016
TI  - Multiple actions of the novel anticonvulsant drug topiramate in the rat subiculum
      in vitro.
AB  - We used an in vitro slice preparation to study whether and how the anticonvulsant
      drug topiramate (TPM, 50-500 microM) modulates the excitability of rat subicular
      neurons that generate action potential bursts mainly caused by voltage-dependent,
      Na+-electrogenesis. Subiculum is a gating structure for outputs originating from
      the hippocampus proper, and thus it may play a role in limbic seizures. In 28/45
      neurons, TPM induced a steady hyperpolarization of the resting membrane potential
      (RMP) that ranged between -2 and -16 mV and was associated with a 24-62% decrease
      of the apparent membrane input resistance. TPM also depressed the ability of
      these cells to generate action potential bursts in response to brief (5-150 ms)
      depolarizing pulses; such an effect was characterized by an increase in the
      amount of intracellular depolarizing current required for eliciting action
      potential bursts, and it also occurred when the TPM-induced steady
      hyperpolarization was compensated by injecting steady depolarizing current. In
      addition TPM reduced by approx. 50% the regular action potential firing elicited
      by prolonged (350-1000 ms) depolarizing pulses (n=15 of 27 neurons). Recovery of
      the TPM-induced changes was not seen during washout for periods of 20-80 min
      (n=7). Both the steady hyperpolarization of the RMP and the input resistance
      decrease elicited by TPM were markedly reduced by the GABAA receptor antagonists
      bicuculline methiodide (10 microM; n=6) or picrotoxin (100 microM; n=2); such an
      effect was associated with a reduction, but not with blockade of the depressant
      action exerted by TPM on burst generation. Our findings indicate that TPM reduces
      subicular cell excitability, and modifies bursting ability and repetitive firing
      properties. These effects may be ascribed to actions on voltage-gated, Na+
      electrogenesis and GABAA receptors. We propose that these changes in excitability
      may all contribute to the anticonvulsant action of TPM in limbic seizures that
      occur in temporal lobe epilepsy patients.

PMID- 9757017
TI  - The genomic organization of the human corticotropin-releasing factor type-1
      receptor.
AB  - We determined the genomic organization of human CRF type-1 receptor (hCRF-R1).
      The gene coding for hCRF-R1 consists of at least 14 exons and spans over 20
      kilobases. hCRF-R1's three reported isoforms originate from the same gene by
      alternative splicing. The first hCRF-R1, which binds to CRF with the highest
      affinity and transduces the most sensitive cAMP accumulation in response to CRF,
      is encoded in a total of 13 exons, the only one excluded being exon 6. The second
      isoform contains an additional 29-amino acid sequence which corresponds to exon
      6. Unlike the first isoform, the third lacks a 40-amino acid sequence,
      corresponding to exon 3. Exon-intron boundaries are the same as that of the
      consensus sequence. Locations of introns in the coding sequence are similar to
      human CRF-R1, rat CRF-R1, human CRF-R2alpha and others belonging to the human
      glucagon receptor family.

PMID- 9757018
TI  - Evaluation of a tissue homogenization technique that isolates nuclei for the in
      vivo single cell gel electrophoresis (comet) assay: a collaborative study by five
      laboratories.
AB  - We evaluated a tissue homogenization technique that isolates nuclei for use in
      the in vivo comet assay. Five laboratories independently tested the technique
      using the liver, kidney, lung, spleen, and bone marrow of untreated and mutagen
      treated male CD-1 mice. The direct mutagen methylmethanesulfonate (MMS) or the
      promutagen diethylnitrosamine (DEN) were injected intraperitoneally at maximum
      tolerated doses. Three and twenty-four hours later, the organs were removed and,
      except for bone marrow, were minced and homogenized and a nuclear suspension was
      prepared. The nuclear suspensions and bone marrow cells were used in the comet
      assay. None of the nuclear suspensions from the non-treated mice induced a
      positive response. All nuclear suspensions derived from the MMS-treated mice and
      those of the liver, kidney, and lung from DEN-treated mice induced positive
      responses in all the laboratories similarly. Reproducibility was demonstrated by
      five replicate studies in one laboratory. Furthermore, the organ-specific
      responses to MMS and DEN reflected the characteristic genotoxicity of the
      chemicals. We concluded from these results that the homogenization technique is a
      valid one to be used for mouse organs in the in vivo comet assay.

PMID- 9757019
TI  - Adrenal steroid regulation of central angiotensin II receptor subtypes and
      oxytocin receptors in rat brain.
AB  - The neuropeptides angiotensin II (AngII) and oxytocin (OT) play important but
      opposing roles in the regulation of sodium appetite in the rat, AngII as a
      stimulatory peptide and OT as an inhibitory peptide. Adrenal steroids increase
      the density of AngII receptors in brain following in vivo administration,
      although the neuroanatomical and subtype specificity have not been thoroughly
      examined. Furthermore, previous studies demonstrate that adrenalectomy (ADX)
      leads to a reduction in OT receptors, although regions associated with sodium
      appetite remain to be examined. In the present study, quantitative receptor
      autoradiography was used to locate regions where perturbations in circulating
      adrenal steroids affect the density of oxytocin receptors and the angiotensin
      receptor subtypes AT1 and AT2. The results show that ADX results in a small, but
      significant decrease in AT1 expression in the paraventricular nucleus of the
      hypothalamus, subfornical organ, and the area postrema. That this effect is
      reversed by either aldosterone or low-dose corticosterone replacement suggests
      that occupancy of the mineralocorticoid receptor is responsible for the steroid
      effect. No changes were observed in AT2 or OT receptors in nuclei associated with
      sodium appetite, indicating that perturbations in adrenal steroids did not affect
      these receptors in brain regions implicated in the control of salt appetite.

PMID- 9757020
TI  - The antioxidant defences of brain mitochondria during short-term forebrain
      ischemia and recirculation in the rat.
AB  - This study evaluated changes in the antioxidant defences of mitochondria induced
      by 30 min of forebrain ischemia and recirculation up to 24 h in rats. Following
      treatment, mitochondria were isolated from two brain subregions: the dorsolateral
      striatum, an area in which there is loss of most neurons, and the paramedian
      cortex in which most neurons are resistant to damage. During ischemia and the
      first few hours of recirculation, the mitochondrial defences were largely
      preserved based on measurements of the activities of the enzymes, superoxide
      dismutase, glutathione peroxidase and glutathione reductase, as well as the
      response of the mitochondria to a subsequent exposure to H2O2 in vitro. However,
      some moderate changes were detected, particularly in the mitochondria from the
      dorsolateral striatum. A decrease of 30% in the activity of superoxide dismutase
      was seen at the conclusion of the ischemic period and a small increase in
      susceptibility to changes induced by H2O2 was detected during early
      recirculation. This latter change preceded and possibly contributed to the
      development of an impairment of respiratory function detected in mitochondria
      from the dorsolateral striatum at 3 h of recirculation. At 24 h of recirculation,
      larger changes were seen in the activities of all three of the enzymes in
      mitochondria from the dorsolateral striatum but not the paramedian cortex that
      was associated with progression to advanced neuronal damage in the former
      subregion.

PMID- 9757021
TI  - Neonatal primary neuronal death induced by capsaicin and axotomy involves an
      apoptotic mechanism.
AB  - To clarify the mechanism of capsaicin-induced primary neuronal cell death,
      newborn and adult rats were given a subcutaneous injection of capsaicin (50
      mg/kg). Neonatal capsaicin injection induced neuronal apoptosis in the trigeminal
      ganglion. Apoptotic neurons had peripheral stacks of long parallel endoplasmic
      reticulum that are characteristic to primary neurons of the B-type, and exhibited
      nucleoplasmic condensation, nuclear shrinkage and cytoplasmic fragmentation.
      Light microscopically, apoptotic neurons exhibited a sign of DNA fragmentation as
      revealed by a nick end labelling method. The proportion of apoptotic cells was
      quite low during the first 12 h after capsaicin injection (<1%), rapidly increase
      to 10.44% by 24 h, and decreased to 0.29% by 48 h. Normal and vehicle control
      levels of apoptosis were <1%. Nerve growth factor (NGF, 0.5 mg/kg) simultaneously
      administered with capsaicin reduced the incidence of apoptosis by about 35% at 24
      h post-injection. Neonatal transection of the infraorbital nerve induced neuronal
      apoptosis similar to that produced by the neonatal capsaicin in the maxillary
      division of the trigeminal ganglion. Unlike capsaicin, however, the neurotomy
      induced apoptosis was seen in neurons of both the A- and B-types. Neither the
      capsaicin injection nor the neurotomy induced apoptosis in adult rats, though
      mitochondrial swelling similar to that seen at 0.5 h after neonatal capsaicin was
      observed after capsaicin injection in adults. The results indicate that the
      capsaicin-induced and nerve injury-induced primary neuronal damages in newborn
      rats share a common final pathway, apoptosis.

PMID- 9757022
TI  - Tissue-specific enhancement and restriction of galanin gene expression in
      transgenic mice by 5' flanking sequences.
AB  - Galanin (GAL) is a 29/30 amino acid residue neuropeptide that regulates a wide
      variety of neuroendocrine functions. Galanin is expressed in specific populations
      of neurons in the hypothalamus and other regions of the brain and in numerous
      peripheral sites. Previous studies in which galanin-reporter genes were
      transfected into neural crest-derived neuroblastoma and other tumor cells
      indicated that cell-specific galanin expression is controlled by gene elements on
      the 5' flanking sequence which enhance and restrict transcriptional activity. To
      determine how the gene sequences act in vivo, we first determined the
      distribution of endogenous galanin gene expression in normal mice. Galanin mRNA
      was detected in several parts of the central nervous system (CNS), and in several
      peripheral organs, including the pituitary, pancreas, small and large intestine,
      adrenal gland, lung, tongue, testes, ovary-fallopian tubes, and uterus, but not
      at detectable levels in the heart, liver, kidney, urinary bladder or skeletal
      muscle. We then created several lines of transgenic mice which contained either 5
      or 0.131 kilobases (kb) of the bovine galanin gene 5' flanking sequence fused to
      the luciferase (luc) reporter gene (5GAL-luc vs. 0.1GAL-luc mice, respectively)
      and compared luciferase activity in these and other organs. In some regions of
      the CNS that expressed high amounts of galanin mRNA, such as the spinal cord,
      hypothalamus, thalamus, and medulla, transgene expression was significantly
      higher in 5GAL-luc vs. 0.1GAL-luc mice, whereas in certain other regions of the
      brain and in all peripheral organs, the ratio was strikingly reversed. It is
      concluded that 5 kb of flanking sequence contains elements that mediate basal
      transcriptional activity in certain parts of the CNS, but also contains sequences
      that restrict expression in many tissues. However, because the larger transgene
      was expressed at very low levels in some peripheral sites of high galanin
      expression such as the pituitary, pancreas, adrenal gland, and intestine, it is
      concluded that sequences on the 5 kb transgene are not sufficient to direct
      expression to these peripheral tissues in mice.

PMID- 9757023
TI  - Homo- and heterosynaptic long-term potentiation in the medial cortex of the
      turtle brain in vitro.
AB  - Long-term potentiation of excitatory synaptic transmission was studied in an in
      vitro turtle brain that manifests spontaneous electrocorticogram activity. We
      show that in the turtle medial cortex, there is evidence of homosynaptic long
      term potentiation in the septum-medial cortex pathway. This potentiation has two
      components, one dependent on NMDA receptor activation and the other independent
      of this receptor and suppressed by nifedipine, an antagonist of voltage-dependent
      Ca2+ channels (VDCCs), as occurs in the CA1 of rat hippocampus. Heterosynaptic
      long-term potentiation was also found in the medial cortex, as a tetanus in the
      septum also increased the cortico medial-cortico medial response. The
      intracellular response of pyramidal cells showed that the medial cortex EPSP
      increased its amplitude paripassu with an increase in the response of evoked
      field potential after tetanic stimulation in the septum.

PMID- 9757024
TI  - Hyperoxia increases paradoxical sleep rhythm in the pontine cat.
AB  - Pontine cat is an ectothermic preparation, whose central temperature can
      artificially be lowered from 36 degrees C to 26 degrees C; this gradual
      hypothermia is accompanied by a dramatic increase in paradoxical sleep (PS). Two
      main hypotheses might explain this result: executive systems of PS might be
      switched on gradually by cold-sensitive thermodetectors, whereas inhibitory
      monoaminergic mechanisms appear to be warm-sensitive. On the other hand, energy
      saving mechanisms peculiar to hypothermia might promote PS appearance. Indeed, in
      normal animals, PS is selectively suppressed both by hyperthermia and hypoxia.
      The inhibitory effect of hypoxia might explain why hypothermia, which protects
      the brain against hypoxic alterations, might facilitate PS. If this last
      hypothesis is correct, the putative increase in cerebral oxygen supply might
      increase PS. For this reason, we submitted eight pontine carotid-deafferented
      cats, kept at the same central temperature (34 +/- 0.5 degrees C: temperature
      clamp) to periodic hyperoxia (PaO2 = 58 +/- 7 kPa) or room air (PaO2 = 17 +/- 2
      kPa) alternatively during 4- or 12-h periods. Hyperoxia induced an 85% increase
      in PS, mainly due to an increase in PS rhythm (PS cycle duration was 65 +/- 4 min
      in normoxia and 45 +/- 4 min in hyperoxia, p<0.0001). In five animals, after
      hyperoxia, PS cycle returned gradually back to control values in 4 to 12 h. These
      findings show that PS is exquisitely sensitive to conditions that impair
      oxidative metabolism. The role of cholinergic executive PS systems as putative
      metabolic-sensitive neurons remains to be established.

PMID- 9757025
TI  - Preproenkephalin gene expression and [Met5]-enkephalin levels in the developing
      rat heart.
AB  - [Met5]-enkephalin, encoded by the preproenkephalin (PPE) gene, serves as a growth
      factor (opioid growth factor, OGF) during cardiac development in addition to its
      role as a neuroregulator. This study examined the ontogeny and relationship of
      gene and peptide expression in the mammalian heart during late embryonic,
      preweaning, and postweaning periods. Values for PPE mRNA of hearts in rats from
      embryonic day 16 (E16) to postnatal day 1 were 33 to 50% of levels found in
      adults. Adult values for the mature heart were comparable to those in the
      caudate, an area of the rat brain rich in PPE mRNA. Message gradually decreased
      during the first postnatal week to 10% of adult values and remained so until
      weaning. PPE mRNA on days 35 and 50 were three- and sevenfold, respectively,
      higher than at 21 days, and in adults was more than 50% greater than at day 50.
      Message for PPE in neonatal heart was regulated rapidly and in a sustained
      fashion by excess opioid agonist (OGF) or blockade of opioid-receptor
      interaction. [Met5]-enkephalin levels increased sevenfold between E18 and E20,
      and another 1.6-fold until birth. Having reached a zenith in the neonate, values
      for enkephalin-like peptide decreased gradually through the 2nd postnatal week,
      and were extremely low in adulthood. Indeed, a 43-fold difference in peptide
      levels was detected between neonatal and adult rat heart. These data provide
      evidence for the expression of a tightly regulated and distinct growth factor
      (OGF) during the crucial periods of cell proliferation and differentiation in the
      mammalian heart, and reveal that the source of OGF is autocrine and/or paracrine.

PMID- 9757026
TI  - Amyloid beta-peptide induces apoptosis-related events in synapses and dendrites.
AB  - Synapse loss in cerebral cortex and hippocampus is a prominent feature of
      Alzheimer's disease (AD) that is correlated with cognitive impairment.
      Postsynaptic regions of dendrites are subjected to particularly high levels of
      calcium influx and oxidative stress as a result of local activation of glutamate
      receptors, and are therefore likely to be sites at which neurodegenerative
      processes are initiated in AD. Data suggest that neurons may die in AD by a
      process called apoptosis which involves a stereotyped series of biochemical
      changes that culminate in nuclear fragmentation, and that amyloid beta-peptide
      (Abeta) may play a role in such apoptosis. We now report that Abeta induces
      apoptosis-related biochemical changes in cortical synaptosomes, and in dendrites
      of cultured hippocampal neurons. Exposure of synaptosomes to Abeta resulted in
      loss of membrane phospholipid asymmetry, caspase activation, and mitochondrial
      membrane depolarization. Cytosolic extracts from synaptosomes exposed to Abeta
      induced chromatin condensation and fragmentation in isolated nuclei indicating
      that signals capable of inducing nuclear apoptosis can be generated locally in
      synapses. Exposure of cultured hippocampal neurons to Abeta resulted in caspase
      activation and mitochondrial membrane depolarization in dendrites and cell
      bodies. A caspase inhibitor prevented Abeta-induced mitochondrial membrane
      depolarization in synaptosomes, and mitochondrial membrane depolarization and
      nuclear apoptosis in cultured hippocampal neurons. Collectively, the data
      demonstrate that apoptotic biochemical cascades can be activated in synapses and
      dendrites by Abeta, and suggest that such 'synaptic apoptosis' may contribute to
      synaptic dysfunction and degeneration in AD.

PMID- 9757027
TI  - Changes in proliferating cell nuclear antigen, a protein involved in DNA repair,
      in vulnerable hippocampal neurons following global cerebral ischemia.
AB  - Proliferating cell nuclear antigen (PCNA) is required for completion of the DNA
      synthesis step of DNA replication as well as nucleotide excision repair (NER) of
      damaged DNA. We investigated the expression of PCNA mRNA and the levels of PCNA
      protein in the adult rat hippocampus following normo- and hypothermic global
      forebrain ischemia. Hypothermia protected the CA1 neurons from ischemic damage. A
      constitutive expression of PCNA mRNA and protein was detected in all hippocampal
      subfields, as well as in other brain regions. During reperfusion, PCNA mRNA
      levels were up-regulated in the vulnerable CA1 subfield at 36 h following
      normothermic ischemia. In hypothermia, this induction appeared already after 18
      h. Following normothermic ischemia, nuclear PCNA immunoreactivity was largely
      abolished during reperfusion in the vulnerable CA1 neurons, prior to cell death.
      In contrast, total PCNA protein content of this region, as measured by Western
      blotting, remained largely unchanged. In the CA3 region, a transient decrease in
      nuclear PCNA immunoreactivity was observed. In the dentate gyrus region, no down
      regulation of nuclear or total PCNA protein was observed during reperfusion.
      Following hypothermic ischemia, the PCNA protein levels did not decrease in any
      of the hippocampal subregions. In contrast, no change in the levels of Ref-1, a
      protein involved in base excision DNA repair (BER), was observed following normo-
      or hypothermic ischemia. Our findings indicate an altered functional state of
      PCNA protein in the ischemia-sensitive CA1 neurons suggesting that DNA repair
      processes are affected in these post-mitotic cells following ischemia. Impaired
      DNA repair may play a role in the development of postischemic neuronal damage.

PMID- 9757028
TI  - Neuroprotection by delayed administration of topiramate in a rat model of middle
      cerebral artery embolization.
AB  - Because topiramate (TPM) suppresses voltage-sensitive Na+ channels and non-N
      methyl-D-aspartate (NMDA) receptors and enhances gamma-aminobutyric acid (GABA)
      mediated inhibition, we tested whether it would protect against cerebral
      ischemia. The right middle cerebral artery (MCA) was embolized by an intra
      arterial injection of autogenous thrombus. Two hours after thrombus injection,
      animals received intra-peritoneal injections (i.p.) of normal saline as control
      (n=6) or alternatively, a low- (20 mg/kg, i.p., n=6) or high-dose (40 mg/kg,
      i.p., n=6) of TPM. Neurological deficit was scored at 2 h and 24 h following the
      ischemic insult. The animals were sacrificed 24 h after ischemia and the coronal
      brain sections were stained with 2% 2,3,5-triphenyltetrazolium chloride (TTC) for
      determination of the percentage of infarct volume. Administration of TPM
      significantly improved the 24-h neurological deficit scores (low dose, 1.75+/
      0.5; high dose, 1.17+/-0.41; p<0.05 for both doses). A reduction in the
      percentage of infarct volume (low dose, 22.9+/-8.9%, p=0.002; high dose 7.6+/
      3.4%, p<0.001) was seen when compared to the controls (infarct size, 54.2+/-9.0%;
      neurobehavior score, 2. 67+/-0.52). Treatment with TPM at the higher dose induced
      more neuroprotection than that at the lower dose (p<0.05). Thus, treatment with
      TPM resulted in a dose- and use-dependent neuroprotective effect, when used 2 h
      after MCA embolization in a rat model of focal ischemia.

PMID- 9757029
TI  - Regulation of PAX-6 gene transcription: alternate promoter usage in human brain.
AB  - We have isolated and characterized the 5'-flanking regulatory region of the human
      PAX-6 gene. Mapping of transcription initiation sites revealed the existence of
      an additional non-coding 5' exon, exon 1A. Functional analyses indicated that PAX
      6 transcription is regulated by two distinct promoters, A and B, resulting in
      alternative transcription of exon 1A or 1B and joint transcription of exons 2 to
      13. While a single initiation site was identified for exon 1A, transcription of
      exon 1B appears to be initiated from more than one site downstream of the
      promoter B-associated TATA motif. Multiple potential binding sites for
      transcription factors were found in the regions of promoter A and B. Although a
      1.1-kb fragment of promoter A and a 1.5 kb fragment of promoter B, which had been
      fused to a reporter gene and transiently expressed in cell lines, displayed
      constitutive promoter activity, transcription of PAX-6 driven by promoter B was
      considerably higher than by promoter A in various regions of human postmortem
      brain. Transcript PAX-6B was primarily expressed in cerebellar cortex, whereas
      relatively low concentrations were detected in other brain areas. Functional
      dissection by serial deletions revealed several clusters of both activating
      elements and cell-selective silencers within the regulatory regions upstream of
      exon 1A and 1B. Coexpression of the promoter B constructs with a vector
      expressing PAX-6 modulated promoter B activity, thus indicating autoregulation by
      PAX-6 transcription. In conclusion, our findings suggest that PAX-6 transcription
      is regulated by alternate usage of promoter A and B, and that in adult human
      brain expression of PAX-6 is primarily controlled by promoter B. Alternate
      promoter usage and differential PAX-6 transcription are likely to play a critical
      role in brain development and neuroplasticity.

PMID- 9757030
TI  - Fatty acid incorporation depicts brain activity in a rat model of Parkinson's
      disease.
AB  - Following pulse labeling with [3H]arachidonic acid ([3H]AA), its incorporation
      pattern in brain reflects regional changes in neurotransmitter signal
      transduction using phospholipase A2, that is, functional activity. In a rat model
      of Parkinson's disease, unilateral 6-hydroxydopamine lesion in the substantia
      nigra, [3H]AA acid incorporation from blood was increased in cerebral cortex,
      caudate putamen, globus pallidus, entopeduncular nucleus, subthalamic nucleus and
      substantia nigra pars reticulata ipsilateral to the lesion. This increased [3H]AA
      incorporation likely reflects disinhibition of basal ganglia and cortical
      circuits secondary to absent inhibitory nigrostriatal dopaminergic input.

PMID- 9757031
TI  - Respiratory responses to chemical stimulation of the parabrachial nuclear complex
      in the rabbit.
AB  - The respiratory role of the parabrachial nuclear complex (PNC) was investigated
      in alpha-chloralose-urethane anesthetized, vagotomized, paralysed and
      artificially ventilated rabbits by means of unilateral microinjections (10-20 nl)
      of 20 mM dl-homocysteic acid. Chemical stimulation elicited three main types of
      site-specific respiratory effects: excitatory, apneustic and inhibitory
      responses. The results suggest that the PNC plays a complex role in the control
      of breathing.

PMID- 9757032
TI  - Learning impairments caused by lesions to the pedunculopontine tegmental nucleus:
      an artifact of anxiety?
AB  - Bilateral N-methyl-d-aspartate lesions of the pedunculopontine tegmental nucleus
      (PPTg) blocked the acquisition of a delayed non-matching to position task (DNMP)
      performed in a T-maze. This acquisition impairment, however, was reversed by pre
      testing injections of diazepam (1 mg/kg). These results, in addition to the
      finding that PPTg lesions elevated anxiety as measured by the elevated plus maze,
      suggest that PPTg is not involved in learning or memory, but in the regulation of
      anxiety.

PMID- 9757033
TI  - Cloning experiments and developmental expression of both melatonin receptor Mel1A
      mRNA and melatonin binding sites in the Syrian hamster suprachiasmatic nuclei.
AB  - The suprachiasmatic nuclei (SCN) are implicated in the control of circadian
      biological rhythms, and especially the melatonin nocturnal synthesis. In numerous
      rodents, melatonin has been shown to feed back on the SCN activity through high
      affinity receptors. In contrast, Syrian hamster SCN activity is unresponsive to
      melatonin injections. As this lack of effect could be linked to a developmental
      loss of SCN melatonin receptors, the goals of the present study were 1) to report
      in Syrian hamster SCN, and pars tuberalis (PT) as a control, a complete pattern
      of the postnatal (PN) development of the melatonin receptor density and 2) to
      investigate whether the regulation of the Mel1a mRNA expression could be
      implicated in the post natal variations of the melatonin binding capacities. We
      first subcloned by PCR a partial cDNA encoding the Mel1a receptor from Syrian
      hamster SCN. Subsequent quantification of Mel1a mRNA expression and melatonin
      receptor density revealed that in the PT and SCN, both Mel1a mRNA expression and
      melatonin binding capacities declined abruptly between PN 0 and PN 8. Afterwards,
      in the PT, both parameters went up until they got stabilized in adulthood.
      Therefore, in the PT, post natal melatonin receptor density variations were
      highly correlated with post natal variations of the Mel1a mRNA expression. In the
      SCN, after PN 8, the melatonin receptor density followed its drop and then
      declined by more than 92% between post natal day 0 (PN 0) and PN 60 (12.11+/-0.
      27 vs. 0.94+/-0.08 fmol/mg protein at PN 0 and PN 60 respectively). In contrast,
      Mel1a mRNA expression only slightly went down after PN 8 and got stabilized in
      adult age at 42% of the birth day expression level. These results show that
      Syrian hamster SCN undergo a dramatic post natal loss of their melatonin
      receptors that could explain the lack of effect of melatonin injections on SCN
      circadian activity. Furthermore, this SCN binding capacities decline could not be
      attributed to an inhibition of the mRNA expression, but rather to a post
      transcriptional blockade of the Mel1a receptor expression.

PMID- 9757034
TI  - Inhibitory action of CGS 21680 on cerebral cortical neurons is antagonized by
      bicuculline and picrotoxin-is GABA involved?
AB  - The possibility of an involvement of endogenously released GABA in the inhibitory
      actions of A1 and A2a adenosine receptor agonists on rat cerebral cortical
      neurons discharges was examined using the GABAA antagonists bicuculline and
      picrotoxin. The A1 agonist N6-cyclopentyladenosine (CPA), the A2a agonist CGS
      21680 and the non-selective receptor agonist, adenosine, depressed neuronal
      firing. Applications of bicuculline or picrotoxin enhanced the spontaneous firing
      rate of cortical neurons, indicating the presence of ongoing GABA-ergic
      inhibition. Antagonism of GABAA receptors blocked the depressant effects of CGS
      21680 on neuronal firing; was without effect on CPA-evoked inhibitions and tended
      to reduce the duration of adenosine-evoked inhibitions. These results suggest
      that the depressant effects of A2a receptor activation are due to an increase in
      GABA-ergic inhibition, likely as a consequence of increased GABA release. GABA
      does not appear to be involved in adenosine A1 receptor-mediated inhibition of
      neuronal firing.

PMID- 9757035
TI  - 1,25-Dihydroxyvitamin D3 receptors in the central nervous system of the rat
      embryo.
AB  - We have mapped areas within the central nervous system (CNS) of the developing
      fetal rat which immunostain for the 1,25-dihydroxyvitamin D3 receptor (VDR). The
      VDR was detected from days 12 to 21 of gestation throughout the CNS;
      immunostaining was particularly intense in the neuroepithelium and within the
      differentiating fields of various areas of the brain. Cells within the spinal
      cord, dorsal root, and other ganglia exhibited positive staining for the VDR. The
      intensity of staining for the VDR diminished or disappeared in the
      neuroepithelium throughout the CNS during the later days of development, while in
      the differentiating fields single VDR immunoreactive cells were observed. The
      presence of the VDR in the CNS was confirmed by in situ hybridization and RNA
      based polymerase chain reaction methods with di-deoxy sequencing of the resultant
      DNA product. These results support the hypothesis that 1, 25-dihydroxyvitamin D3,
      through interactions with the VDR, may play a role in the development of the CNS.

PMID- 9757036
TI  - Temperature-dependent effect of zolpidem on the GABAA receptor-mediated response
      at recombinant human GABAA receptor subtypes.
AB  - The effects of zolpidem on the two forms of recombinant human GABAA receptors
      (alpha1beta2gamma2s and alpha3beta2gamma2s) at different temperatures were
      functionally investigated, using the whole-cell patch recording configuration. In
      both forms, zolpidem potentiated the response to GABA in a concentration
      dependent manner. At 16 degrees C, the apparent dissociation constant (KD) values
      for the alpha1beta2gamma2s and alpha3beta2gamma2s forms were 3.7 x 10(-8) and 5.6
      x 10(-7) M, respectively. When the temperature was increased to 36 degrees C, the
      KD values for the alpha1beta2gamma2s and alpha3beta2gamma2s forms were 2.1 x 10(
      7) and 1.5 x 10(-6) M, respectively. Although the affinity ratio was reduced from
      15.1 to 7.1-fold the selectivity of zolpidem for the alpha1beta2gamma2s still
      remained at 36 degrees C.

PMID- 9757037
TI  - Prostaglandin E2 increases proenkephalin mRNA level in rat astrocyte-enriched
      culture.
AB  - The effect of prostaglandin E2 (PGE2) on proenkephalin (proENK) mRNA expression
      in primary cultured rat astrocytes was studied. The proENK mRNA level was
      significantly increased about 3.3-fold 4 h after PGE2 (10 microM) treatment and
      this increase was potentiated by the pre-treatment with cycloheximide (CHX; 15
      microM) about 1.7-fold as much as PGE2 alone treated cells. The pretreatment with
      staurosporine (1 microM) completely inhibited the increase of PGE2-induced proENK
      mRNA level, although only a partial inhibition of PGE2-induced proENK mRNA level
      (approximately 1.5-fold) by H89 (10 microM) was observed. The increase of PGE2
      induced proENK mRNA level was not affected by the pretreatment with PD98059 (1,
      5, and 10 microM), omega-conotoxin GIVA (1 microM), nimodipine (1 microM),
      calmidazolium (1 microM), or KN-62 (1 microM). In addition to the proENK mRNA
      level, PGE2 also increased c-Fos (approximately 4.3-fold), Fra-1 ( approximately
      3.8 fold), and Fra-2 (approximately 8.2-fold) protein levels at 4 h after drug
      treatment. However, c-Jun, JunB, and JunD protein levels were not affected by
      PGE2. Indeed, PGE2 failed to up-regulate c-jun mRNA expression as well as its
      protein product. Surprisingly, although three Jun proteins were not induced by
      PGE2, AP-1 and ENKCRE-2 DNA binding activities were increased by PGE2,
      (approximately 5 and approximately 2.8-fold, respectively) and which were
      effectively reduced by CHX (approximately 2.5 and 2-fold, respectively). In
      western blot analyses, PGE2 enhanced the phosphorylation of CREB (approximately
      2.6-fold at 1 h), and CHX showed a potentiative effect on PGE2-induced CREB
      phosphorylation ( approximately 1.7 fold at 1 h) which is similar to the action
      on proENK mRNA regulation. Our results suggest that PGE2 increases proENK mRNA
      expression via activating serine/threonine protein kinase such as PKA, but not
      calcium/calmodulin dependent protein kinase and MAPK. In addition,
      phosphorylation of CREB rather than the increase of AP-1 may have a possible role
      at least early stage in PGE2-induced proENK mRNA level and CHX-evoked
      potentiation.

PMID- 9757038
TI  - Calcitonin gene-related peptide as a GH secretagogue in human and rat pituitary
      somatotrophs.
AB  - To elucidate the role of calcitonin gene-related peptide (CGRP) in regulating
      pituitary function, we investigated the effects of CGRP and the related peptide
      adrenomedullin (AdM) on the secretion of growth hormone (GH) in vitro from human
      pituitary adenoma cells, rat pituitary tumor (GH3) cells, and normal rat
      pituitary cells. In 3 of 5 human somatotroph adenomas, GH secretion was
      stimulated by CGRP (1-100 nM). In one case of somatotroph adenoma, GH release was
      observed following the addition of 10 nM GHRH and 10 nM CGRP. The addition of
      CGRP or AdM (1 pM-10 nM) evoked GH secretion from GH3 cells with a bell-shaped
      distribution curve. CGRP (100 pM) caused the maximum increase of GH secretion
      (172+/-14 (mean+/-S.D.)% of control). The addition of CGRP8-37, an antagonist of
      CGRP type 1 receptors, inhibited the stimulatory effect of AdM but did not
      inhibit the effect of CGRP. The addition of CGRP and AdM evoked moderate GH
      secretion from normal rat pituitary cells. These results suggested that CGRP is a
      new GH secretagogue in human and rat pituitary tumor cells.

PMID- 9757039
TI  - Attenuation of the lordosis-inhibiting effects of 8-OH-DPAT by TFMPP and
      quipazine.
AB  - Regularly cycling, proestrous female rats received infusions of 200 ng of the
      serotonin (5-HT) 1A receptor agonist, (+/-) 8-hydroxy 2-(di-n-propylamino)
      tetralin-HBr (8-OH-DPAT), or 200 ng 8-OH-DPAT and 1000 or 2000 ng of N-(3
      trifluoro-methylphenyl) piperazine hydrochloride (TFMPP) or 2-(1-piperazinyl)
      quinoline dimaleate (quipazine). Infusions were made bilaterally into the
      ventromedial nucleus of the hypothalamus (VMN). Animals receiving 200 ng 8-OH
      DPAT exhibited a decline in lordosis behavior following infusion. Rats receiving
      8-OH-DPAT and 1000 or 2000 ng quipazine or TFMPP were protected from the lordosis
      inhibiting effects of 8-OH-DPAT, alone. Although both quipazine and TFMPP act on
      multiple 5-HT receptors, they overlap in their agonist action at 5-HT2 receptors.
      Consequently, these results provide further evidence supporting the contention
      that within the VMN, both 5-HT1A and 5-HT2 receptor subtypes contribute to the
      modulation of lordosis behavior in the female rat. The data are discussed in
      terms of the relative potency of 5-HT at 5-HT receptors mediating inhibition and
      facilitation of lordosis behavior.

PMID- 9757040
TI  - Biphasic modulatory action of the selective sigma receptor ligand SR 31742A on N
      methyl-D-aspartate-induced neuronal responses in the frontal cortex.
AB  - The technique of intracellular recording was used to assess the effect of SR
      31742A, a selective sigma receptor ligand, on N-methyl-d-aspartate (NMDA) and (+/
      )-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor
      mediated responses in pyramidal cells of the rat medial prefrontal cortex in
      vitro brain slice preparations. Bath application of SR 31742A produced a biphasic
      effect on NMDA responses: SR 31742A facilitated and inhibited NMDA-induced inward
      current at low (0.01, 0.05 and 0.1 microM) and higher (0.5, 1 and 10 microM)
      concentrations, respectively. The potentiating effect reached the peak (366%) at
      0.1 microM, with an estimated EC50 value of 23 nM. Correspondingly, SR 31742A
      also produced a similar biphasic modulatory action on excitatory postsynaptic
      potentials or currents (EPSPs/EPSCs) evoked by electrical stimulation of the
      forceps minor. In contrast, SR 31742A produced a modest potentiation of AMPA
      responses at the concentrations from 0.01 to 1 microM. The potentiating action of
      SR 31742A on NMDA-receptor mediated neurotransmission may account for, at least
      partially, its antipsychotic and cognitive-enhancing potential, whereas the
      inhibitory action on NMDA responses at higher concentrations may be related to
      the purported neuroprotective action of sigma receptor ligands.

PMID- 9757041
TI  - Behavioral changes and expression of heat shock protein hsp-70 mRNA, brain
      derived neurotrophic factor mRNA, and cyclooxygenase-2 mRNA in rat brain
      following seizures induced by systemic administration of kainic acid.
AB  - Kainic acid-induced seizures in rats represent an established animal model for
      human temporal lobe epilepsy. However, it is well-known that behavioral responses
      to the systemic administration of kainic acid are inconsistent between animals.
      In this study, we examined the relationship between expression of genes,
      neuropathological damage, and behavioral changes (seizure intensity and body
      temperature) in rats after systemic administration of kainic acid. The
      considerable differences in the response to kainic acid-induced seizures were
      observed in rats after a single administration of kainic acid (12 mg/kg i.p.).
      There was no detection of the expression of heat shock protein hsp-70 mRNA and
      HSP-70 protein in brain of vehicle-treated controls and in animals exhibiting
      weak behavioral changes (stage 1-2). A moderate expression of hsp-70 mRNA was
      detected throughout all regions (the pyramidal cell layers of CA1-3 and dentate
      gyrus) of the hippocampus, the basolateral, lateral, central and medial amygdala,
      the piriform cortex, and the central medial thalamic nucleus of rats that
      developed moderate seizures (stage 3-4). Marked expression of hsp-70 mRNA was
      detected in the all regions (cingulate, parietal, somatosensory, insular,
      entorhinal, piriform cortices) of cerebral cortex and all regions of hippocampus,
      and the central medial thalamic nucleus of the rats that developed severe
      seizures (stage 4-5). In addition, marked HSP-70 immunoreactivity was detected in
      the pyramidal cell layers of CA1 and CA3 regions of hippocampus, all regions
      (cingulate, parietal, somatosensory, insular, piriform cortices) of cerebral
      cortex, and the striatum of rats that developed severe seizures (stage 4-5).
      Furthermore, a marked expression of cyclooxygenase-2 (COX-2) mRNA and brain
      derived neurotrophic factor (BDNF) mRNA levels by kainic acid-induced behavioral
      seizures (stage 3-4 or stage 4-5) was detected in all hippocampal pyramidal cell
      layers, granule layers of dentate gyrus, piriform cortex, neocortex, and
      amygdala. The present study suggest that the behavioral changes (seizure
      intensity and body temperature) and neuropathological damage after systemic
      administration of kainic acid are inconsistent between animals, and that these
      behavioral changes (severity of kainic acid-induced limbic seizures) might be
      correlated with gene expression of hsp-70 mRNA, COX-2 mRNA, and BDNF mRNA in rat
      brain.

PMID- 9757042
TI  - Effects of various N-terminal fragments of glucagon-like peptide-1(7-36) on food
      intake in the neonatal chick.
AB  - Recently, the suppressive effect on food intake by the central administration of
      glucagon-like peptide-1 (GLP-1) has been confirmed in both rats and chicks. The
      importance of the N-terminal amino acid, histidine, for the bioactivity of GLP
      1(7-36) in the central nervous system was suggested, though the role for C
      terminal amino acids in the central nervous system has not been reported. The
      present study was done to elucidate the central effect of N-terminal fragments of
      GLP-1(7-36) on food intake of the neonatal chick. Intracerebroventricular
      (i.c.v.) administration of mammalian GLP-1(7-36) inhibited food intake of chicks,
      but the fragments of GLP-1(7-16) and GLP-1(7-26) did not show the suppressive
      effect on food intake. Furthermore, the extended fragments, GLP-1(7-30) and GLP
      1(7-33), also had no effects on food intake. It is concluded that C-terminal
      amino acids of GLP-1(7-36) have an important role for the bioactivity in the
      central nervous system with special reference to feeding behavior.

PMID- 9757043
TI  - Isolation of mouse vomeronasal receptor genes and their co-localization with
      specific G-protein messenger RNAs.
AB  - Four mouse vomeronasal receptors (mV1Rs) have been isolated by similarity to rat
      vomeronasal receptor (V1R) motifs. The four mV1Rs identified in this study are
      members of two distinct subfamilies. Specific in situ hybridization probes (ISH)
      derived from the 3' non-coding regions of the mV1R genes, were used to detect
      expression of a single receptor and probes from the homologous coding regions
      were used to detect expression of subfamily members. The ISH results showed that
      the mV1Rs expressing neurons were scattered in the middle/upper layer of the
      vomeronasal organ (VNO) sensory epithelium in serial VNO sections but were
      excluded from the deeper layers of the VNO sensory epithelium and these neurons
      were found to co-express the mRNA for the G-protein Galphai2, and were distinct
      from the deeper layers of the VNO sensory epithelium where the mRNA for Galphao
      positive neurons was located.

PMID- 9757045
TI  - Segmental effect of NMDA block in the dorsal horn on the pressor reflex.
AB  - The purpose of this study was to examine the influence of NMDA receptor blockade
      in the dorsal horn of adjacent spinal segments as it pertains to the pressor
      reflex evoked by static contraction and stretch of skeletal muscle. In this
      preparation, cats were anesthetized and the afferent fibers mediating the pressor
      reflex entered the spinal cord via the L7 dorsal root. Blockade of dorsal horn
      NMDA receptors at L6 and L7 attenuated the pressor reflex evoked by static
      contraction and muscle stretch. However, NMDA block in the L6 dorsal horn alone
      failed to alter the peak increase in MAP produced by static contraction and
      muscle stretch, but the initial pressor response evoked by static contraction was
      attenuated. These data support the hypothesis that the pressor reflex is
      partially mediated by activation of NMDA receptors in the dorsal horn, and this
      occurs at multiple spinal segments. Further, these data suggest that activation
      of NMDA receptors plays an important role in initiating the rise in arterial
      pressure produced by static contraction of skeletal muscle.

PMID- 9757044
TI  - Calretinin-like immunoreactivity in the regenerating periodontal ruffini endings
      of the rat incisor following injury to the inferior alveolar nerve.
AB  - Regeneration of calretinin (CR)-like immunoreactive (IR) nerve fibers was
      investigated in the periodontal ligament of the rat lower incisor following
      resection of the inferior alveolar nerve (IAN). In addition, the degeneration and
      regeneration processes of periodontal nerve fibers were examined by
      immunohistochemistry for protein gene product 9.5 (PGP 9.5), a general neuronal
      marker. In normal animals, the periodontal nerve fibers showing PGP 9.5-like
      immunoreactivity (LI) formed either periodontal Ruffini endings with expanded
      arborization and thin free nerve endings in the alveolar half of the ligament.
      Thick CR-IR nerve fibers also appeared in a dendritic fashion in the same region,
      but thin CR-IR nerve fibers were rarely observed. Five days following resection
      of the IAN, a major population of PGP 9.5-IR and all CR-IR nerve fibers
      disappeared except for some thin PGP 9.5-IR nerves in the periodontal ligament.
      Regenerated PGP 9.5-IR nerve fibers appeared around 7 days following resection,
      in contrast to a very small number of regenerated CR-IR nerve fibers. Around 14
      21 days following resection, the number and terminal morphology of regenerated
      PGP 9.5-IR nerve fibers were comparable to those observed in normal animals, but
      the number of regenerated CR-IR nerve fibers was still smaller than that of
      normal animals. The number of regenerated CR-IR nerve fibers increased to return
      to normal by 56 days following injury. The delay of expression of CR-LI in the
      regenerated periodontal Ruffini endings suggests that functional recovery of
      periodontal Ruffini endings occurred after the completion of the regeneration of
      periodontal nerve fibers.

PMID- 9757046
TI  - Extracellular dopamine and catabolites in rat striatum during lactic acid
      perfusion as determined by in vivo microdialysis.
AB  - Many experimental studies concerning hypoxia or ischemia have reported a decrease
      in intra/extracellular pH and massive dopamine (DA) release in the striatum. The
      present work investigated whether the increase in striatal extracellular DA is
      related to acidification or to lactate production. Striatal perfusion of lactic
      acid (pH 5.5) by microdialysis in conscious freely-moving rats induced an
      increase in extracellular concentrations of DA and catabolites, homovanillic acid
      (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC), as a probable result of
      acidification. Perfusion with sodium lactate (pH 7.4) failed to modify DA and
      catabolite release, whereas orthophosphoric acid produced the same effect as
      lactic acid. As lactic acidosis is known to induce a displacement of iron from
      its uptake sites, the possible role of this metal in response to acidosis was
      studied by perfusing ferrozine, an iron complexing agent, at the same time as
      lactic acid. The results showed that ferrous ions are involved in the process and
      suggested that oxygen free radicals play a role in the extracellular release of
      DA. Thus, lactic acid perfusion in rat striatum would appear to be a useful model
      for in vivo studies of the mechanisms responsible for increases in extracellular
      DA during hypoxia and ischemia.

PMID- 9757047
TI  - Receptors and effects of the inhibitory neuropeptide somatostatin in microglial
      cells.
AB  - The expression of receptors for the neuropeptide somatostatin was investigated in
      cultured immunocytochemically pure rat microglial cells. By the reverse
      transcriptase-polymerase chain reaction, the mRNAs for the receptor subtypes
      sst2, sst3 and sst4, but not sst1 and sst5 could be detected. To show that these
      receptors were functionally active, the effects of somatostatin and the
      metabolically stable, receptor subtype (2, 3 and 5) selective derivative
      octreotide (SMS 201-995, Sandostatin) on protein phosphorylation and
      proliferation were evaluated. Somatostatin induced the tyrosine phosphorylation
      of a 95 kDa protein in microglia. Furthermore, somatostatin or octreotide
      inhibited the basal as well as the GM-CSF-(granulocyte macrophage colony
      stimulating factor) or the IL-3-(interleukin-3)-stimulated proliferation of
      microglial cells. This effect was dose-dependent, with a half maximum activity of
      about 0.2-0.3 nM. Somatostatin was relatively stable in the cultures due to
      protease inhibitors in the serum. The results indicate that microglial cells are
      targets for the widespread neuropeptide somatostatin and that its receptors can
      transduce complex signals to microglia.

PMID- 9757048
TI  - Orphanin FQ stimulates prolactin and growth hormone release in male and female
      rats.
AB  - Intracerebroventricular administration of Orphanin FQ (5.5, 55 or 550 pmol)
      caused a dose-related increase in prolactin secretion in both male and female
      rats and stimulated GH secretion in males. The magnitude of the prolactin
      secretory response was greater in females than in males. These effects of OFQ on
      prolactin and growth hormone release are the same as the stimulatory effects of
      the endogenous opioid peptides.

PMID- 9757049
TI  - Amphetamine administration improves neurochemical outcome of lateral fluid
      percussion brain injury in the rat.
AB  - This study examined the effects of the administration of D-amphetamine on the
      regional accumulation of lactate and free fatty acids (FFAs) after lateral fluid
      percussion (FP) brain injury in the rat. Rats were subjected to either FP brain
      injury of moderate severity (1.9 to 2.0 atm) or sham operation. At 5 min after
      injury, rats were treated with either d-amphetamine (4 mg/kg, i.p.) or saline. At
      30 min and 60 min after brain injury, brains were frozen in situ, and cortices
      and hippocampi were excised at 0 degrees C. In the saline-treated brain injured
      rats, levels of lactate were increased in the ipsilateral left cortex and
      hippocampus at 30 min and 60 min after injury. These increases were attenuated by
      the administration of D-amphetamine at 5 min after lateral FP brain injury. At 30
      and 60 min after FP brain injury, increases in the levels of all individual FFAs
      (palmitic, stearic, oleic and arachidonic acids) and of total FFAs were also
      observed in the ipsilateral cortex of the saline-treated injured rats. These
      increases in the ipsilateral cortex and hippocampus were also attenuated by the
      administration of d-amphetamine. Neither levels of lactate nor levels of FFAs
      were increased in the contralateral cortex in the saline-treated injured rats at
      30 min or 60 min after FP brain injury. The levels of lactate and FFAs in the
      contralateral cortex were also unaffected by the administration of D-amphetamine.
      These results suggest that the attenuation of increases in the levels of lactate
      and FFAs in the ipsilateral cortex and hippocampus may be involved in the
      amphetamine-induced improvement in behavioral outcome after lateral FP brain
      injury.

PMID- 9757050
TI  - Molecular cloning and pharmacological characterization of an atypical gerbil
      angiotensin II type-1 receptor and its mRNA expression in brain and peripheral
      tissues.
AB  - In the gerbil brain, most of the [125I]Sarcosine1-Angiotensin II binding sites
      are atypical, not sensitive to displacement with selective Angiotensin II AT1 and
      AT2 receptor ligands. A similar atypical binding profile exists in the gerbil
      kidney, where binding is highly expressed. We isolated a 2197 base pair clone
      from a gerbil kidney cDNA library which encodes a 359 amino acid protein with
      higher than 90% homology to other mammalian angiotensin II AT1 receptors. When
      expressed in COS-7 cells, stimulation by Angiotensin II of both the cloned gerbil
      receptor or the human AT1 receptor enhanced IP3 production to a similar degree.
      In COS-7 cells, the gerbil receptor also had a ligand affinity profile similar to
      that of the human AT1 receptor, but showed greatly reduced affinity for losartan
      (IC50=3480+/-174 nM). In the gerbil brain, in situ hybridization revealed
      receptor mRNA in circumventricular organs, selective hypothalamic, midbrain and
      brain stem areas, and in the hippocampus, where high mRNA expression was detected
      in the stratum pyramidale of the CA1 and CA2 subfields, and in the stratum
      granulosum of the dentate gyrus. The expression pattern of receptor mRNA
      corresponded well with that of atypical [125I]Sar1-Ang II binding. In situ
      hybridization and Southern blot experiments using riboprobes against the open
      reading frame and the 3'-untranslated region of the cloned gerbil Ang II receptor
      cDNA suggest that gerbils have, like other rodents, two AT1 receptor subtypes.
      The receptor mRNA distribution of the cloned gerbil Ang II receptor corresponds
      to the distribution of AT1A receptors described in other rodent species.

PMID- 9757051
TI  - Catecholamine concentrations in rat nasal mucus are modulated by trigeminal
      stimulation of the nasal cavity.
AB  - Olfactory mucus provides the perireceptor environment in which the initial steps
      of olfactory signal transduction occur [5]. Extrinsic autonomic and trigeminal
      innervation controls mucus secretion and may release neurotransmitters into nasal
      mucus [13]. We quantitated catecholamines in rat nasal mucus and found that
      catecholamine levels first increased and then declined with trigeminal
      stimulation. These data indicate that catecholamine levels are regulated in nasal
      mucus and could modulate the odor sensitivity of olfactory sensory neurons.

PMID- 9757053
TI  - Electrophysiological and neuropharmacological study of tectoreticular pathways in
      lampreys.
AB  - Tectoreticular (TR) cells along the diencephalic-mesencephalic border are the
      origin of prominent crossed and uncrossed pathways that project to the middle
      (MRRN) and posterior (PRRN) rhombencephalic reticular nuclei in juvenile and
      adult lampreys [I.C. Zompa, R. Dubuc, Diencephalic and mesencephalic projections
      to rhombencephalic reticular nuclei in lampreys, Brain Res. (1998) in press.].
      This study investigated the synaptic contacts between TR axons and the reticular
      cells. Intracellular recordings were carried out in reticular neurones (n=124)
      while microstimulating the TR regions. Tectoreticular inputs were recorded in all
      reticular cells studied (248 PSPs); although stronger responses were evoked in
      the MRRN neurones. The majority of responses were excitatory, but increasingly
      mixed and inhibitory when recorded in the middle and caudal part of the reticular
      nuclei. The excitation had the shortest onset latencies and sharpest slopes
      measured in both reticular nuclei, while the inhibition was longer and smoother.
      The characteristics of TR inputs to different reticular cell types is also
      presented. The transmission of evoked responses was isolated to the crossed and
      uncrossed TR pathways by studying the effects of 1% Xylocaine ejections and
      surgical lesions. The TR inputs were transmitted to reticular cells through
      monosynaptic and polysynaptic contacts. The synaptic transmission involved
      excitatory amino acids, acting through AMPA and NMDA receptors, while the
      inhibition was glycinergic. Comparisons with other sensory systems in lampreys
      are discussed.

PMID- 9757052
TI  - Nitric oxide as a putative messenger molecule in the crayfish olfactory midbrain.
AB  - NADPH-d histochemistry was used to investigate presumptive nitric oxide synthase
      (NOS)-containing neurons in the crayfish olfactory midbrain. Three anatomically
      different types of local olfactory interneurons exhibiting NADPH-d activity were
      observed: two pairs of large interneurons as well as positively stained globuli
      cells. Branches derived from the large interneurons were confined to the
      ipsilateral olfactory lobe and accessory lobe, but only a few branches innervated
      the olfactory lobe glomeruli. Local field potential recordings on the olfactory
      lobe showed that administration of SNP or SIN-1 (10-4 M) into the brain had
      reversible inhibitory effects on electrically-evoked responses of unidentified
      neuronal cell populations.

PMID- 9757054
TI  - The 5-HT1A agonist 8-OH-DPAT increases the number of spike-wave discharges in a
      genetic rat model of absence epilepsy.
AB  - The effects of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)
      tetralin (8-OH-DPAT) on the epileptiform activity has been investigated in adult
      WAG/RIJ rats. Either intraperitoneal (0.1-0.5 mg/kg) or intracerebroventricular
      (2-20 microg/rat) administration of 8-OH-DPAT caused marked, dose-dependent
      increases in the number and mean cumulative duration of spike-wave discharges.
      These effects were attenuated by NAN-190, a 5-HT1A receptor antagonist. These
      data indicate that serotonergic system regulates the epileptiform activity in
      this genetic model of human absence epilepsy.

PMID- 9757055
TI  - Substance P- and CGRP-immunoreactive fibers in the chicken carotid bodies after
      nodose ganglionectomy and midcervical vagotomy.
AB  - The chicken carotid body is richly innervated by branches from the vagus nerve
      immunostained with the monoclonal antibody TuJ1 to neuron-specific class III beta
      tubulin. Furthermore, peptidergic nerve fibers are densely distributed in and
      around the carotid body. After transection of the vagus nerve proximal to the
      nodose ganglion, TuJ1-immunoreactive fibers did not change in density but
      substance P- and CGRP-immunoreactive fibers were conspicuously decreased in and
      around the carotid body. After removal of the nodose ganglion, TuJ1
      immunoreactive fibers markedly diminished and substance P- and CGRP
      immunoreactive fibers almost disappeared. These results indicate that the vast
      majority of substance P- and CGRP-immunoreactive fibers in the chicken carotid
      body originate from the vagal ganglia.

PMID- 9757056
TI  - Regulation of the preprosomatostatin gene by cyclic-AMP in cerebrocortical
      neurons.
AB  - The gene coding for preprosomatostatin (ppSom), the molecular precursor of
      somatostatin (Som), is regulated at the level of transcription by calcium ions
      and cyclic-AMP [F. Baldino, S. Fitzpatrick-McElligott, T. O'Kane, I. Gozes,
      Hormonal regulation of somatostatin, Synapse 2 (1988) 317-325; M.R. Montminy,
      M.J. Low, L. Tapia-Arancibia, Cyclic AMP regulates somatostatin mRNA accumulation
      in primary diencephalic cultures and in transfected fibroblast cells, J.
      Neurosci. 6 (1986) 1171-1176.], or by agents which increase intracellular levels
      of cAMP directly, such as forskolin [M.R. Montminy, M.J. Low, L. Tapia-Arancibia,
      Cyclic AMP regulates somatostatin mRNA accumulation in primary diencephalic
      cultures and in transfected fibroblast cells, J. Neurosci. 6 (1986) 1171-1176.].
      Transcriptional induction of the ppSom gene as examined in PC12 cells,
      transfected fibroblasts and primary diencephalic cultures, requires the highly
      conserved cAMP response element (CRE), which confers gene responsiveness to cAMP
      [M. Comb, N. Mermod, S.E. Hyman, Proteins bound at adjacent DNA elements act
      synergistically to regulate human proenkephalin cAMP inducible transcription,
      EMBO J. 7 (1988) 3793-3805; T. Tsukada, J.S. Fink, G. Mandel, Identification of a
      region in the human vasoactive intestinal polypeptide gene responsible for
      regulation by cyclic AMP, J. Biol. Chem. 262 (1987) 8743-8747.]. The ppSom gene
      is subject to stringent regulation during cerebrocortical development in vivo;
      however, little information is available regarding ppSom gene regulation by
      neurotransmitters or second-messengers in cortical neurons. We used primary
      cerebrocortical cell cultures from fetal mice to examine the dose-response and
      time-course of ppSom gene expression in response to the cyclic-AMP analogs,
      dibutyrl-cAMP (dbcAMP), and 8-bromo-cAMP (8-BrcAMP). We report a dose-response
      for both analogs in the range of 0.1-10 mM. Dose-response studies using agents
      which directly stimulate intracellular cAMP synthesis (forskolin) or inhibit its
      breakdown (3-isobutyl 1-methyl xanthine) were also performed. We observed an
      apparent synergistic effect on ppSom expression when used in combination. An
      increase in ppSom mRNA levels was observed by 4 h, with a maximal response at 12
      24 h. No change in ppSom mRNA levels was observed in response to phorbol
      myristate acetate (PMA). Our findings confirm the specificity of ppSom gene
      regulation by cAMP and Ca2+ ions, and demonstrate the utility of using primary
      cerebrocortical cultures for the study of somatostatin gene expression by
      neurotransmitters and second-messengers as a model of human neurologic disorders.

PMID- 9757057
TI  - GABAB receptor stimulation phase-shifts the mammalian circadian clock in vitro.
AB  - The mammalian circadian clock in the suprachiasmatic nucleus (SCN) generates 24-h
      rhythms in vitro. Here we show that the GABAB agonist baclofen resets the SCN
      pacemaker in vitro in a phase-dependent manner: advances were induced at
      zeitgeber time (ZT) 6, and delays were induced at ZT 22. Both effects were
      blocked the GABAB antagonist, 2-hydroxysaclofen, while the GABAA antagonist,
      bicuculline was ineffective. Thus, the SCN pacemaker is sensitive to resetting by
      GABAB stimulation.

PMID- 9757058
TI  - A role of climbing fibers in regulation of flocculonodular lobe protein kinase C
      expression during vestibular compensation.
AB  - The behavioral recovery from unilateral labyrinthectomy (UL) in rats is
      accompanied by asymmetric expression of Protein kinase C (PKC) in parasagittal
      regions of the flocculonodular lobe within 6 h after UL, which resolves to the
      control, symmetric pattern within 24 h. These changes consist of a regionally
      selective increase in the number of PKC-immunopositive Purkinje cells
      contralateral to the lesion. This study tested the hypotheses (1) that climbing
      fiber innervation inhibits PKC expression and (2) that climbing fibers are
      essential for the observed changes in PKC expression within 6 h after UL. The
      patterns of flocculonodular lobe Purkinje cell PKCdelta expression were analyzed
      6 h post-operatively in both UL and sham-operated that had been treated
      previously with 3-acetylpyridine to destroy the inferior olive. These data were
      compared with previous results from rats with an intact olive. The results
      suggest that at least two signals regulate the zonal distribution of Purkinje
      cell PKCdelta expression in the flocculonodular lobe during the early period of
      compensation from UL. Climbing fiber activation appears to reduce PKC expression,
      while extraolivary mechanisms appear to up-regulate PKC expression. It is
      suggested that the climbing fiber signals may act as a molecular 'filter' or
      'automatic gain control' which adjusts the contributions of these kinases to
      synaptic plasticity within the context of the background activity of climbing
      fibers.

PMID- 9757059
TI  - Volatile anesthetics directly activate baseline S K+ channels in aplysia neurons.
AB  - The actions of halothane on serotonin-sensitive potassium channels (S K+
      channels) were studied in sensory neurons of Aplysia. The normalized open
      probability of S K+ channels was increased by clinical concentrations of
      halothane in cell-attached and excised patches from neurons of the pleural
      ventrocaudal cluster. No voltage-dependence of channel activation by halothane
      was observed. Pre-treatment of neurons with 8-bromo-cAMP (8-Br-cAMP) or
      nordihydroguaiaretic acid (NDGA) had no effect on the relative level of channel
      activation by halothane. S K+ channels that were activated by arachidonic acid
      could also be activated by halothane and exhibited closely similar amplitude
      distributions of open channel current. Results from these experiments showed that
      S K+ channel activation by halothane did not depend on second messenger
      modulation of channel activity. We conclude that it is likely that halothane
      directly activates S K+ channels.

PMID- 9757060
TI  - The expression of voltage-dependent calcium channel beta subunits in human
      hippocampus.
AB  - The beta subunits of voltage-dependent calcium channels (VDCC) modulate the
      electrophysiology and cell surface expression of pore-forming alpha1 subunits. In
      the present study we have investigated the distribution of beta1,beta2,beta3 and
      beta4 in the human hippocampus using in situ hybridization (ISH) and
      immunohistochemistry. ISH studies showed a similar distribution of expression of
      beta1,beta2 and beta3 subunit mRNAs, including labelling of the dentate granule
      cell layer, all CA pyramidal regions, and the subiculum. Relatively low levels of
      expression of beta1 and beta2 subunit mRNAs correlated with low protein
      expression in the immunocytochemical (ICC) studies. There was a relative lack of
      beta4 expression by both ISH and ICC in the CA1 region, compared with high levels
      of expression in the subiculum. Immunostaining for beta1 and beta2 subunits was
      weak and relatively homogeneous throughout the hippocampus. The beta3 and beta4
      subunits appeared to be more discretely localized. In general, beta3
      immunoreactivity was moderate both in cell bodies, and as diffuse staining in the
      surrounding neuropil. Strongest staining was observed in mossy fibres and their
      terminal region in the CA3 stratum lucidum. In contrast, beta4-immunoreactivity
      in the neuropil showed intense dendritic localisation. Unlike the other subunits,
      beta4-immunoreactivity was absent from CA1 pyramidal neurones but was present in
      a small population of interneurone-like cells. The localisation of beta3 and
      beta4 may represent presynaptic and postsynaptic compartments in some populations
      of hippocampal neurones. Comparison of beta subunit distribution with previously
      published data on alpha1 subunits indicates certain neuronal groups and
      subcellular compartments in which the subunit composition of native pre- and
      postsynaptic VDCC can be predicted.

PMID- 9757061
TI  - Effects of ethanol on rat somatosensory cortical neurons.
AB  - In this study, we characterized the local effects of ethanol (EtOH) on
      postsynaptic potentials (PSPs) and membrane properties of layer II-III (L2-3) and
      layer V (L5) somatosensory cortical neurons. Intracellular recordings were done
      using the in vitro slice preparation of rat somatosensory cortex. Our results
      show that EtOH exerts local effects on cortical cell membrane at physiologically
      relevant concentrations. A predominant effect of EtOH was to reduce excitability
      of L2-3 and L5 neurons by increasing the rheobase, decreasing input resistance
      and repetitive firing, reducing PSPs amplitude and the probability of evoking
      action potentials. Early (6 ms) and late (18 ms) PSP components were affected
      differentially by EtOH, the late components being more suppressed. Overall, EtOH
      mediated suppression of PSPs was stronger in L5 neurons. Cortical neurons were
      divided into three subtypes: regular spiking adapting (RS-A), regular spiking non
      adapting (RS-NA) and bursting (D-IB) neurons. PSPs evoked in RS-A neurons were
      more sensitive to EtOH suppressant effects. EtOH effects on input resistance were
      distributed differentially among the three groups of neurons. These results
      support the notion that EtOH disrupts higher processing of somatosensory
      information via a differential alteration of cortical neuron's membrane
      properties and synaptic transmission.

PMID- 9757062
TI  - Glutamate-induced cytotoxicity in PC12 pheochromocytoma cells: role of oxidation
      of phospholipids, glutathione and protein sulfhydryls revealed by bcl-2
      transfection.
AB  - Incubation of mock-transfected PC12 rat pheochromocytoma cells (PC12) for 2 h
      with increasing concentrations of glutamate caused progressive loss of viability
      (e.g., 67% with 15 mM glutamate). In contrast, the viability of bcl-2-transfected
      cells (PC12/bcl-2) was unaffected by glutamate. Neither PC12 nor PC12/bcl-2 cells
      showed a significant incidence of apoptosis in response to glutamate.
      Conventional phospholipid analysis by high-performance TLC and phosphorous
      determination showed no significant changes in the phospholipid composition of
      either cell line incubated with </=15 mM glutamate. Phospholipid peroxidation was
      quantified in the cells using our newly developed method based on fluorescence
      HPLC analysis of metabolically incorporated oxidation-sensitive and fluorescent
      fatty acid, cis-parinaric acid. Unlike previous studies that measured total
      phospholipid oxidation, this novel technology permitted quantitation of oxidative
      stress in different classes of labeled phospholipids (the amount of labeled
      phospholipids in the cells did not exceed 1% of total phospholipids). Significant
      peroxidation of phosphatidylcholine and phosphatidylethanolamine occurred in PC12
      cells treated with >5 mM glutamate. The peroxyl radical initiator 2,2'-azobis(2,4
      dimethylvaleronitrile) caused a pronounced loss of all major phospholipid classes
      in PC12 cells, but no loss of cell viability. No phospholipid peroxidation was
      detected in PC12/bcl-2 cells incubated with </=15 mM glutamate or with 2, 2'
      azobis(2,4-dimethylvaleronitrile). These results directly demonstrate that
      peroxidation of membrane phospholipids is not responsible for the cytotoxicity of
      glutamate in PC12 cells. Total cellular thiol, protein thiol and GSH reserves
      were quantified by a previously described electron paramagnetic resonance
      spectrometric method. Total thiols were ca. 1.5-fold greater in PC12/bcl-2 than
      in PC12 cells. Glutamate (</=5 mM) caused a progressive and equally significant
      decrease in total thiols and GSH in both PC12 and PC12/bcl-2 cells. High
      glutamate concentrations caused oxidation of protein sulfhydryls in PC12 cells,
      but not in PC12/bcl-2 cells. The results suggest that the changes in cellular
      milieu caused by bcl-2 gene transfection protect PC12 cells from the toxic
      effects of glutamate in a manner consistent with prevention of protein sulfhydryl
      oxidation.

PMID- 9757063
TI  - Glial fibrillary acidic protein (GFAP) immunoreactivity in enteric ganglia of the
      chick embryo.
AB  - We examined by immunohistochemistry the expression of glial fibrillary acidic
      protein (GFAP) in enteric ganglia of the chick embryo, using a polyclonal
      antibody. The morphology of enteric ganglion cells was examined by electron
      microscopy. Faint GFAP immunoreactivity was detected in ganglion cells and cell
      processes from around day 7 in ovo. Later in development the intensity of the
      immunofluorescence increased and it became more evident that immunoreactive small
      ganglion cells (interpreted as primitive glial cells), and their processes,
      surrounded larger negative cell profiles (interpreted as primitive neuronal
      cells); GFAP immunofluorescence was also evident in intramuscular and mucosal
      nerve trunks. In colocalization experiments, GFAP immunoreactivity was detected
      in a proportion of HNK-1/N-CAM immunoreactive ganglion cells, in both the
      myenteric and submucosal plexus. In addition, we observed GFAP immunoreactive
      nerves in wholemount preparations of chick gut from as early as day 4.5 in ovo.
      In the ganglionated nerve of Remak, GFAP immunoreactive satellite and Schwann
      cells were in evidence from day 5 of incubation. Neuronal markers, such as
      neurofilament, have been detected very early in development in neural crest cell
      populations in chick enteric ganglia. In contrast, the expression of markers of
      the glial phenotype has previously been observed only in the late stages of
      embryonic development. From our experiments, we conclude that neuronal and glial
      phenotypes are immunohistochemically distinct from as early as day 4.5 of
      incubation, even if by ultrastructural criteria glial cells are clearly
      distinguishable from neurons only after day 16 in ovo.

PMID- 9757065
TI  - Human prodynorphin gene generates several tissue-specific transcripts.
AB  - The present study analyzes the transcription of the human prodynorphin gene.
      Transfection experiments indicate that promoter activity for the 2.8 kb 'brain
      type' human prodynorphin mRNA resides in the DNA region located 140-180 b
      upstream of the exon 1/intron A boundary and not 1.2 kb further upstream, as
      proposed by others [S. Horikawa, T. Takai, M. Toyosato, H. Takahashi, M. Noda, H.
      Kakidani, T. Kubo, T. Hirose, S. Tanayama, H. Hayashida, T. Miyata, S. Numa,
      Isolation and structural organization of the human preproenkephalin B gene,
      Nature 306, 1983, pp. 611-614]. The new data locates the human prodynorphin gene
      promoter for the brain-type mRNA in a position corresponding to the position of
      the rat prodynorphin gene promoter [J. Douglass, C.T. McMurray, J.E. Garett, J.P.
      Adelman, L. Calavetta, Characterization of the rat prodynorphin gene, Mol.
      Endocrinol. 3, 1989, pp. 2070-2078]. Three previously not described types of
      human prodynorphin mRNA of the same size, 2.8 kb, one expressed in fetal brain
      and two others in testis, were characterized in this study. These mRNAs are
      generated by alternative splicing of novel 5'-uppermost exons and transcription
      is probably initiated from other promoters. Human neuroblastoma SH-SY5Y and SK-N
      MC cell lines previously used in studies of gene transcription have the 2.8 kb
      prodynorphin mRNA of adult brain alongside a more abundant, shorter 2.3 kb
      transcript. The latter transcript was also found in testis and in fetal brain. It
      lacked the 5'-part of the 2.8 kb mRNA including the signal peptide encoding
      sequence. The complex pattern of prodynorphin gene expression and its functional
      consequences are issues for further studies.

PMID- 9757064
TI  - Decreased expression of GABAA receptor alpha6 and beta3 subunits in stargazer
      mutant mice: a possible role for brain-derived neurotrophic factor in the
      regulation of cerebellar GABAA receptor expression?
AB  - The cerebellar granule cells of the spontaneous recessive mutant mouse strain,
      stargazer (stg/stg), fail to express brain-derived neurotrophic factor mRNA. This
      deficit is exclusive to these neurons and is believed to underlie the motor
      irregularities displayed by stg/stg, though the molecular basis for their
      phenotype has still to be resolved. Brain-derived neurotrophic factor has been
      shown to play a role in the postnatal maturation of cerebellar granule cells.
      Differentiation of these neurons, postnatally, is characterised by a switch in
      their GABAA receptor subunit expression profile. Notably, the GABAA receptor
      alpha6 subunit, which is specific to these neurons, becomes detectable at
      postnatal days 10-14 (P10-14). To determine whether cerebellar GABAA receptor
      expression has been compromised in stg/stg mice, the expression levels of GABAA
      receptor alpha1, alpha6, beta2 and beta3 subunits were compared between stg/stg
      mice and the appropriate wild-type background strain, C57BL/6J (+/+). By
      quantitative immunoblotting, it was found that the expression of the alpha6 and
      beta3 subunits was 23+/-8% and 38+/-12% (mean+/-S.E.M., n=6) of control (+/+)
      levels, respectively. In contrast, the expression of the alpha1 and beta2
      subunits was not significantly different from controls, being 116+/-11% and 87+/
      24% (mean+/-S.E.M., n=6) of +/+ levels, respectively. Total specific [3H]Ro15
      4513 binding activity detected in cerebellar membranes prepared from stg/stg was
      not significantly different from +/+ mice. However, the benzodiazepine agonist
      insensitive subtype of [3H]Ro15-4513 binding activity, a pharmacological motif of
      alpha6 subunit-containing GABAA receptors, was lower in stg/stg mice relative to
      the +/+ strain which correlated with the lowered level of alpha6 subunit
      expression. Thus, we have identified an abnormality in the GABAA receptor profile
      of stg/stg mutant mice that might underpin its irregular phenotype.

PMID- 9757066
TI  - A tachykinin NK1 receptor antagonist, CP-122,721-1, attenuates kainic acid
      induced seizure activity.
AB  - Substance P (SP) can play an important role in neuronal survival. To analyze the
      role of SP in excitotoxicity, kainic acid (KA) was administered to rats and in
      situ hybridization was used to analyze the levels of the SP encoding
      preprotachykinin-A (PPT-A) mRNA in striatal and hippocampal subregions 1, 4, and
      24 h and 7 days after KA. In striatum and piriform cortex, PPT-A mRNA peaked 4 h
      after KA while in hippocampus, levels peaked after 24 h. KA caused seizures and
      neuronal toxicity as indicated by a reduction of the number of neurons in the
      hippocampal CA1 subregion after 7 days. KA was later administered alone or
      following pretreatment with the tachykinin NK1 receptor antagonist CP-122,721-1
      (0.3 mg/kg). The pretreatment decreased seizure activity and a negative
      correlation was found between seizure activity and survival of CA1 neurons.
      Conclusively, treatment with CP-122,721-1 has a seizure inhibiting property and
      may possibly counteract KA-induced nerve cell death in CA1.

PMID- 9757067
TI  - The increase in angiotensin type-2 receptor mRNA level by glutamate stimulation
      in cultured rat cortical cells.
AB  - The changes in the angiotensin type-2 (AT2) receptor mRNA level during glutamate
      neurotoxicity in cultured rat cortical cells are examined to assess the possible
      involvement of AT2 receptor in cell injury. The day 10-14 cortical neurons were
      exposed to glutamate at a toxic concentration of 100 microM for 15 min. The
      viability of the culture was reduced by 60% after 24 h. AT2 receptor mRNA was
      then increased 2-fold after exposure to glutamate, while the maximum increase was
      observed in a dose-dependent manner (50-1000 microM) 3 h after glutamate
      stimulation. AT2 receptor binding also increased 3-12 h after glutamate exposure.
      The results suggest that the increase in the AT2 receptor preceded to some extent
      the insult of the cell after exposure. The increase in the mRNA level was
      suppressed by MK-801, N-methyl-D-aspartate (NMDA) receptor antagonist, thus
      indicating the possible involvement of NMDA receptor. The increase in the mRNA
      level was also antagonized by N-nitro L-arginine methyl-ester, a nitric oxide
      synthase inhibitor. The hemoglobin, a nitric oxide trap, inhibited the increase
      in the mRNA level. These results suggest that the increase in the mRNA level is
      associated with the nitric oxide synthesis by glutamate exposure. The viability
      of cortical cells after glutamate stimulation was partially restored by the AT2
      receptor antagonist and by the antisense oligonucleotide for the AT2 receptor.
      The present results thus suggest that the AT2 receptor may in some way be related
      to one of the processes in cell injury caused by glutamate.

PMID- 9757068
TI  - Differentially expressed genes in hippocampal cell cultures in response to an
      excitotoxic insult by quinolinic acid.
AB  - The NMDA-type glutamate receptor agonist quinolinic acid (QA), which causes
      tissue lesions in the rat brain as well as cell loss in neuronal cultures, is
      widely used in models of glutamate excitotoxicity. The aim of this study was to
      evaluate the alterations in gene expression in a primary hippocampal cell culture
      after exposure to QA. By means of differential mRNA display, we were able to
      pinpoint as many as 23 bands which appeared to be upregulated after a 6-h
      treatment with quinolinic acid. The differential expression of 13 cDNAs could be
      confirmed by dot blot and/or Northern analysis. Of the cDNAs, the p112 regulatory
      subunit of the 26S proteasome, a PDGF-associated protein and the glia-derived
      protease nexin PN-1 could be identified. The results provide emphasis to the
      participation of proteolysis and protease inhibition in neurodegenerative
      processes.

PMID- 9757069
TI  - The inhibition of human neuronal K+ currents by general anesthetic agents is
      altered by extracellular K.
AB  - We demonstrate for the first time that the extracellular potassium concentration
      influences the inhibition of human neuronal delayed rectifier potassium currents
      by general anesthetics. This observation suggests a modulatory role for
      extracellular potassium ions in the action of some general anesthetic agents.

PMID- 9757070
TI  - Methamphetamine-induced increase in striatal NF-kappaB DNA-binding activity is
      attenuated in superoxide dismutase transgenic mice.
AB  - Methamphetamine injection (x4 with 2-h interval) caused dose-dependent activation
      of striatal NF-kappaB activity. Striatal NF-kappaB binding increased
      significantly at 1-3 h after the last injection of methamphetamine (10 mg/kg,
      i.p. x4). This induction of striatal NF-kappaB activity was significantly
      attenuated in Cu, Zn-superoxide dismutase transgenic mice in a gene dosage
      dependent fashion. The present results suggest that reactive oxygen species
      generated by methamphetamine injections can activate striatal NF-kappaB DNA
      binding during this drug-induced toxic process.

PMID- 9757071
TI  - Interleukin-1 induces c-Fos immunoreactivity in primary afferent neurons of the
      vagus nerve.
AB  - Peripheral administration of bacterial endotoxin, an immune stimulant, induces
      evidence of activation in vagal primary afferent neurons. To determine whether
      interleukin-1beta (IL-1beta) is part of the molecular pathway leading to this
      activation, we assessed the expression of the neuronal activation marker c-Fos in
      vagal primary afferent neurons after intraperitoneal injections of IL-1beta (2
      microg/kg). IL-1beta, but not vehicle, induced c-Fos expression, demonstrating
      that IL-1beta is likely an important signal from the immune system to the vagus
      nerve, and thus the brain.

PMID- 9757073
TI  - Effects of weaning and restraint stress on glucocorticoid receptor binding
      capacity in limbic areas of domestic pigs.
AB  - Changes in glucocorticoid receptor (GR) binding in different brain areas were
      investigated in neonatal and adult pigs exposed to psychological stress (weaning)
      and a physical stressor (repeated snaring). The GR binding was significantly
      decreased 4 days after weaning in both the hippocampus and the amygdala, but
      there were no changes in the hypothalamus. Repeated snaring of adult pigs
      resulted in a significant diminished GR binding only in the hippocampus.

PMID- 9757074
TI  - Effects of cocaethylene on dopamine and serotonin synthesis in Long-Evans and
      Sprague-Dawley brains.
AB  - We examined the behavioral and neurochemical effects of cocaethylene treatment in
      Long-Evans (LE) and Sprague-Dawley (SD) rats. Cocaethylene-induced behaviors were
      significantly less in LE rats. Cocaethylene caused an inhibition of dopamine
      synthesis in the caudate nucleus and nucleus accumbens that was equivalent in
      both rat lines. Serotonin synthesis was also suppressed by cocaethylene
      treatment, however this phenomenon was less pronounced when compared with the
      effects on dopamine synthesis.

PMID- 9757075
TI  - Alterations in the density of excrescences in CA3 neurons of hippocampus in rats
      subjected to self-stimulation experience.
AB  - Self-stimulation (SS) rewarding experience induced alterations in the density of
      excrescences in the apical dendrites of CA3 neurons were studied in adult male
      Wistar rats. SS experience was provided daily for an hour over a period of 10
      days, through bipolar stainless steel electrodes implanted bilaterally in lateral
      hypothalamus and substantia nigra-ventral tegmental area. The results revealed a
      significant (P<0.001) increase in the number of excrescences in both main shaft
      and sub branches of the apical dendrites in SS experienced group compared to
      control groups of rats. The increased number of excrescences in CA3 neurons might
      be due to an enhancement in the synaptic transmission in the mossy fiber pathway
      following SS experience.

PMID- 9757076
TI  - Negative inotropic vagal preganglionic neurons in the nucleus ambiguus of the
      cat: neuroanatomical comparison with negative chronotropic neurons utilizing dual
      retrograde tracers.
AB  - The vagal postganglionic controls of cardiac rate and left ventricular
      contractility are mediated by separate intracardiac ganglia, the sino-atrial (SA)
      and cranio-ventricular (CV) ganglia, respectively. We injected a different
      retrograde tracer into each of these ganglia (in the same animal) and
      subsequently examined the brain for the presence of single labeled or double
      labeled vagal preganglionic neurons. Retrogradely labeled cells from either
      ganglion were found exclusively in the ventrolateral nucleus ambiguus (NA-VL).
      There was considerable overlap in the distribution of labeled cells from either
      ganglion, however fewer than 3% of labeled neurons were double labeled. The data
      are consistent with the hypothesis that the preganglionic controls of cardiac
      rate and left ventricular contractility are mediated by largely separate but
      overlapping groups of cardioinhibitory neurons originating from the NA-VL. These
      neurons have parallel but morphologically independent pathways projecting to the
      SA and CV ganglia. Physiological experiments are needed to support this
      hypothesis.

PMID- 9757077
TI  - Time course for kindling-induced changes in the hilar area of the dentate gyrus:
      reactive gliosis as a potential mechanism.
AB  - Recurrent seizure activity induced during kindling has been reported to cause an
      increase in the hilar area of the dentate gyrus of the hippocampus. To date, very
      little is known about the mechanism of this increase. This study investigated the
      time course for kindling-induced changes in the hilar area of the dentate gyrus
      at seven days, one month, and two months post-kindling. Hilar area of the dentate
      gyrus was significantly increased by approximately 46% at seven days and remained
      elevated at one month, but declined back to control levels by two months. Glial
      fibrillary acidic protein (GFAP) immunostaining was also evaluated at the same
      time points to determine whether kindling-induced changes in the hilar area of
      the dentate gyrus are related to kindling-induced glial cell changes. Increases
      in hilar GFAP immunostaining by approximately 57% were observed at seven days and
      at one month post-kindling, but not at two months post-kindling. These findings
      indicate that kindling-induced changes in the hilar area of the dentate gyrus and
      kindling-induced glial cell changes follow a similar time course, and that
      kindling-induced glial cell changes may mediate the observed changes in the hilar
      area of the dentate gyrus.

PMID- 9757078
TI  - Prevention of DOI-mediated wet dog shakes by inhibitors of nitric oxide synthase.
AB  - The purpose of this study was to determine if (+/-)-1-(2, 5-dimethoxy-4
      iodophenyl)-2-aminopropane (DOI)-induced wet dog shakes (WDS) required the
      involvement of nitric oxide synthases (NOS). Systemic administration of the
      general NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME), but not its d
      isomer, and the neuronal NOS (nNOS) inhibitor 7-nitroindazole completely blocked
      DOI-mediated WDS in a dose dependent manner. The data provides evidence that
      serotonin 5HT2 receptors are coupled to nNOS activation in the rat brain.

PMID- 9757079
TI  - Reaction centre photochemistry in cyanide-treated photosystem II.
AB  - EPR was used to study the triplet state of chlorophyll generated by radical pair
      recombination in the photosystem II (PSII) reaction centre. The spin state of the
      non-haem Fe2+ was varied using the CN--binding method (Y. Sanakis, V. Petrouleas,
      B.A. Diner, Biochemistry 33 (1994) 9922-9928) and the redox state of the quinone
      acceptor (QA) was changed from semi-reduced to fully reduced (F.J.E. van Mieghem,
      W. Nitschke, P. Mathis, A.W. Rutherford, Biochim. Biophys. Acta 977 (1989) 207
      214). It was found that the triplet was not detectable using continuous wave EPR
      when QA- was present irrespective of the spin-state of the Fe2+. It was also
      found that the triplet state became detectable by EPR when the semiquinone was
      removed (by reduction to the quinol) and that the triplet observed was not
      influenced by the spin state of the Fe2+. Since it is known from earlier work
      that the EPR detection of the triplet reflects a change in the triplet lifetime,
      it is concluded that the redox state of the quinone determines the triplet
      lifetime (at least in terms of its detectability by continuous wave EPR) and that
      the magnetic state of the iron, (through the weakly exchange-coupled QA- Fe2+
      complex) is not a determining factor. In addition, we looked for polarisation
      transfer from the radical pair to QA- in PSII where the Fe2+ was low spin. Such
      polarisation is seen in bacterial reaction centres under comparable conditions.
      In PSII, however, we were unable to find evidence for such polarisation of the
      semiquinone. It is suggested that both the short triplet lifetime in the presence
      of QA- and the lack of polarised QA- might be explained in terms of the electron
      transfer mechanism for triplet quenching involving the semiquinone which was
      proposed previously (F.J.E. van Mieghem, K. Brettel, B. Hillmann, A. Kamlowski,
      A.W. Rutherford, E. Schlodder, Biochemistry 34 (1995) 4798-4813). It is suggested
      that this mechanism may occur in PSII (but not in purple bacterial reaction
      centres) due the triplet-bearing chlorophyll being adjacent to the pheophytin at
      low temperature as suggested from structural studies (F.J.E. van Mieghem, K.
      Satoh, A.W. Rutherford, Biochim. Biophys. Acta 1058 (1992) 379-385).

PMID- 9757080
TI  - The triplet state of the FMO complex of the green sulfur bacterium
      Prosthecochloris aestuarii studied with single-crystal EPR.
AB  - Triplet-electron paramagnetic resonance (EPR) spectra were obtained of single
      crystals of the FMO complex of the green sulfur bacterium Prostecochloris
      aestuarii. The experiments support the results presented in a previous paper
      (Louwe et al., J. Phys. Chem. 101 (1997) 11280), which showed that the
      experimental optical spectra of this pigment-protein complex are best reproduced
      by assuming that one bacteriochlorophyll (BChl 3) is energetically isolated and
      that this BChl is the triplet-carrying BChl of the FMO complex at cryogenic
      temperatures for low excitation density. When comparing the experimental and
      simulated data sets of the triplet-EPR spectra in single crystals, the best fit
      is obtained for two triplet states, one localized at BChl 3 and the other at BChl
      1. The existence of two different triplet states is traced to the relatively high
      excitation power necessary to observe the small triplet-EPR signal of the FMO
      single crystals.

PMID- 9757081
TI  - Paracoccus denitrificans cytochrome c oxidase: a kinetic study on the two- and
      four-subunit complexes.
AB  - Cytochrome c oxidase from Paracoccus denitrificans has been purified in two
      different forms differing in polypeptide composition. An enzyme containing
      polypeptides I-IV is obtained when the purification procedure is performed in
      beta-d-dodecylmaltoside. If, however, Triton X-100 is used to purify the enzyme
      under otherwise identical conditions, an enzyme is obtained containing only
      subunits I-II. The two enzymes are undistinguishable by optical spectroscopy but
      show significant differences in the transient and steady-state time regimes, as
      studied by stopped-flow spectroscopy. The observed differences, however, are not
      due to removal of subunits III and IV, but rather to a specific effect of Triton
      X-100 which appears to affect cytochrome c binding. From these results it is not
      expected that subunits III and IV play any significant role in cytochrome c
      binding and, possibly, in the subsequent electron transfer processes. The results
      also suggest that both electrostatic and hydrophobic interactions may be
      important in the initial electron transfer process from cytochrome c.

PMID- 9757082
TI  - Triplet energy transfer in bacterial photosynthetic reaction centres.
AB  - [3-vinyl]-132-OH-bacteriochlorophyll a has been selectively exchanged against
      native bacteriochlorophyll a in the monomer binding sites at the A- and B-branch
      of the photosynthetic reaction centre from Rhodobacter sphaeroides. Transient
      absorption difference measurements were performed on these samples over a
      temperature range from 4.2 to 300 K with 20 ns time resolution. Specifically the
      decay of the primary donor triplet state, 3P870, as well as the rise and decay
      rates of the carotenoid triplet state, 3Car (spheroidene), were measured. The
      observed rates revealed a thermally activated carotenoid triplet formation
      corresponding to the decay of the primary donor triplet state. The activation
      energies for the triplet energy transfer process were 100(+/-10) cm-1 for
      reaction centers from wild-type Rhodobacter sphaeroides 2.4.1, with and without
      exchange of the monomeric bacteriochlorophyll on the electron transfer-active
      branch, BA. For reaction centers from Rhodobacter sphaeroides R26.1 with both
      monomers exchanged against [3-vinyl]-132-OH-bacteriochlorophyll a, and subsequent
      spheroidene reconstitution the activation energy was 460(+/-20) cm-1. These
      activation energies correspond to the energy difference between the triplet
      states of the accessory BChl monomer, BB, and the primary donor when native BChl
      a or [3-vinyl]-132-OH-BChl a is present in the BB binding site. In all samples
      the 3Car formation rates were bi-phasic over a large temperature range. A fast
      temperature-independent rate was observed on the wavelength of the carotenoid
      triplet-triplet absorption which dominated at very low temperatures.
      Additionally, a slower temperature-independent 3Car formation rate was observed
      at low temperatures which could be explained with the assumption of heterogeneity
      in the energy barrier (3BB) and/or the primary donor triplet state (3P870). A
      tunneling mechanism as proposed earlier by Kolaczkowski (PhD thesis, Brown
      University, 1989) is not only unnecessary but also incompatible with the
      available experimental data.

PMID- 9757083
TI  - Flash-induced changes in buffering capacity of reaction centers from
      photosynthetic bacteria reveal complex interaction between quinone pockets.
AB  - A novel method was applied to determine light-induced protonation in reaction
      centers from photosynthetic purple bacteria. Changes in buffering capacities upon
      flash excitation were detected in (0.03% Triton X-100) detergent solution of
      reaction centers from Rhodobacter (Rb.) sphaeroides and Rb. capsulatus wild type
      and mutant strains with empty or occupied secondary quinone (QB) binding sites in
      the presence of an external electron donor. The light-induced differences in
      buffering capacities between pH 4 and 11 were analyzed in terms of protonatable
      residues. Due to its differential nature, this method is more sensitive to the
      position and shift of pKa of the individual groups than the direct method based
      on proton uptake measurements. Out of the four different ionizable residues which
      were used to fit the curves, the two groups with apparent (dark) pKa values
      between 8.4-8.8 and 9.5-10.0 (depending on the species and conditions)
      disappeared when the native ubiquinone10 was replaced by menadione at the primary
      quinone (QA) binding site of Rb. sphaeroides or when the key protonatable
      residues (L212Glu and L213Asp) were replaced by non-protonatable alanines in the
      QB binding site of the AA+M43D mutant from Rb. capsulatus. The experimentally
      observed acidic and neutral residues remained unchanged. These results obtained
      from modifications in both quinone sites reveal the origin of the alkaline pH
      groups: they reflect the interaction of QA- and the cluster of ionizable residues
      around L212Glu in the QB binding pocket. The involvement of two residues with
      close pKa values reflects the complex titration of the cluster. The interaction
      between the quinone pockets is best described qualitatively as a network of
      ionizable residues extending from the QA site to the QB site.

PMID- 9757084
TI  - The two spectroscopically different short wavelength protochlorophyllide forms in
      pea epicotyls are both monomeric.
AB  - The spectral properties of the protochlorophyllide forms in the epicotyls of dark
      grown pea seedlings have been studied in a temperature range, from 10 to 293 K
      with conventional fluorescence emission and excitation spectroscopy as well as by
      fluorescence line narrowing (FLN) at cryogenic temperatures. The conventional
      fluorescence techniques at lower temperatures revealed separate bands at 628, 634
      636, 644 and 655 nm. At room temperature (293 K) the 628 and 634-636 nm emission
      bands strongly overlapped and the band shape was almost independent of the
      excitation wavelength. Under FLN conditions, vibronically resolved fluorescence
      spectra could be measured for the 628 and 634-636 nm bands. The high resolution
      of this technique excluded the excitonic nature of respective excited states and
      made it possible to determine the pure electronic (0,0) range of the spectra of
      the two components. Thus it was concluded that the 628 and 634-636 nm (0,0)
      emission bands originate from two monomeric forms of protochlorophyllide and the
      spectral difference is interpreted as a consequence of environmental effects of
      the surrounding matrix. On the basis of earlier results and the data presented
      here, a model is discussed in which the 636 nm form is considered as an enzyme
      bound protochlorophyllide and the 628 nm form as a protochlorophyllide pool from
      which the substrate is replaced when the epicotyl is illuminated with continuous
      light.

PMID- 9757085
TI  - Structure of 3,4-dichloroisocoumarin-inhibited factor D.
AB  - Factor D (D) is a serine protease essential in the activation of the alternative
      complement pathway. Only a few of the common serine protease inhibitors inhibit
      D, binding covalently to the serine hydroxyl of the catalytic triad. 3,4
      Dichloroisocoumarin (DCI) is a mechanism-based inhibitor which inhibits most
      serine proteases and many esterases, including D. The structure of the
      enzyme:inhibitor covalent adduct of D with DCI, DCI:D, to a resolution of 1.8 A
      is described, which represents the first structural analysis of D with a
      mechanism-based inhibitor. The side chain of the ring-opened DCI moiety of the
      protein adduct undergoes chemical modification in the buffered solution,
      resulting in the formation of an alpha-hydroxy acid moiety through the
      nucleophilic substitution of both Cl atoms. The inhibited enzyme is similar in
      overall structure to the native enzyme, as well as to a variety of isocoumarin
      inhibited trypsin and porcine pancreatic elastase (PPE) structures, yet notable
      differences are observed in the active site and binding mode of these small
      molecule inhibitors. One region of the active site (residues 189-195) is
      relatively conserved between factor D, trypsin, and elastase with respect to
      amino-acid sequence and to conformation. Another region (residues 214-220)
      reflects the amino-acid substitutions and conformational flexibility between
      these enzymes. The carbonyl O atom of the DCI moiety was found to be oriented
      away from the oxyanion hole, which greatly contributes to the stability of the
      DCI:D adduct. The comparisons of the active sites between native factor D, DCI
      inhibited factor D, and various inhibited trypsin and elastase (PPE) molecules
      are providing the chemical bases directing our design of novel, small-molecule
      pharmaceutical agents capable of modulating the alternative complement pathway.

PMID- 9757086
TI  - Integrated software for a macromolecular crystallography synchrotron beamline.
AB  - A package of software has been produced for the operation of the synchrotron
      beamline X12-C at the National Synchrotron Light Source at Brookhaven National
      Laboratory. Years of observing common user mistakes has enabled the production of
      software that reduces user errors significantly. Users of the beamline
      communicate with all the experimental apparatus, including both the data
      collection equipment and the beamline components, including the monochromator,
      through an easy-to-use graphical user interface (GUI). Important features of the
      system are (1) its modularity, so that different underlying programs or different
      apparatus can be incorporated easily; (2) its ease of use, minimizing both user
      errors and training effort; and (3) that most of the experimental operations and
      parameters are logged automatically, again minimizing errors and facilitating
      more-or-less automatic reduction of the data. Features of the software are useful
      enough to have been incorporated into operations at other synchrotron beamlines.

PMID- 9757088
TI  - The refined structure of dUTPase from Escherichia coli.
AB  - Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase, E.C. 3.6. 1.23)
      catalyzes the hydrolysis of dUTP to dUMP and pyrophosphate and is involved in
      nucleotide metabolism and DNA synthesis. A crystal of the recombinant E. coli
      enzyme, precipitated from polyethylene glycol mixtures in the presence of
      succinate at pH 4.2, was used to collect synchrotron diffraction data to 1.9 A
      resolution, in space group R3, a = b = 86.62, c = 62.23 A. Mercury and platinum
      derivative data were collected at wavelengths to optimize the anomalous
      contribution. The resulting 2.2 A MIRAS phases differed from the final set by 40
      degrees on average and produced an excellent map which was easy to interpret. The
      model contains 132 water molecules and refined to an R value of 13.7%. 136
      residues have clear electron density out of 152 expected from the gene sequence.
      The 16 C-terminal residues are presumably disordered in the crystal lattice. The
      monomer is a 'jelly-roll' type, containing mostly beta-sheet and only one short
      helix. The molecule is a tight trimer. A long C-terminal arm extends from one
      subunit and encompasses the next one within the trimer contributing to its beta
      sheet. Conserved sequence motifs common among dUTPases, previously suggested to
      compose the active site and confirmed in a recent study of the dUDP complex, are
      located at subunit-subunit interfaces along the threefold axis, in parts of the
      beta-sheet and in loop regions. A similar molecular architecture has recently
      been found in two other trimeric dUTPases.

PMID- 9757089
TI  - Modified phased translation functions and their application to molecular-fragment
      location.
AB  - Direct methods at high resolution have depended on the resolution of atomic like
      features in the map. At data resolutions more typical for protein structures (2-3
      A) individual atoms may not be resolved, so larger features must be identified.
      At one extreme the whole molecule may be located using the diffraction magnitudes
      alone by the molecular-replacement method. At the other extreme it is possible to
      locate individual residues in a well phased map. In this paper an intermediate
      problem is addressed: the location of multi-residue fragments on the basis of
      weak phase information. An agreement function based on the mean-squared
      difference between model and map over a masked region is shown to be more
      effective than a simple overlap integral, and may be efficiently calculated by
      Fourier methods. The techniques are compared using poorly phased electron-density
      maps at approximately 3 A for the proteins RNAse and O6-methylguanine-DNA
      methyltransferase.

PMID- 9757090
TI  - Structure of the C-type lectin carbohydrate recognition domain of human
      tetranectin.
AB  - Tetranectin (TN) is a C-type lectin involved in fibrinolysis, being the only
      endogenous ligand known to bind specifically to the kringle 4 domain of
      plasminogen. TN was originally isolated from plasma, but shows a wide tissue
      distribution. Furthermore, TN has been found in the extracellular matrix of
      certain human carcinomas, whereas none or little is present in the corresponding
      normal tissue. The crystal structure of full-length trimeric TN (2.8 A
      resolution) has recently been published [Nielsen et al. (1997). FEBS Lett. 412,
      388-396]. The crystal structure of the carbohydrate recognition domain (CRD) of
      human TN (TN3) has been determined separately at 2.0 A resolution in order to
      obtain detailed information on the two calcium binding sites. This information is
      essential for the elucidation of the specificity of TN towards oligosaccharides.
      TN3 crystallizes as a dimer, whereas it appears as a monomer in solution. The
      overall fold of TN3 is similar to other known CRDs. Each monomer is built of two
      distinct regions, one region consisting of six beta-strands and two alpha
      helices, and the other region is composed of four loops harboring two calcium
      ions. The calcium ion at site 1 forms an eightfold coordinated complex and has
      Asp116, Glu120, Gly147, Glu150, Asn151, and one water molecule as ligands. The
      calcium ion at site 2, which is believed to be involved in recognition and
      binding of oligosaccharides, is sevenfold coordinated with ligands Gln143,
      Asp145, Glu150, Asp165, and two water molecules. One sulfate ion has been located
      at the surface of TN3, forming contacts to Glu120, Lys148, Asn106 of a symmetry
      related molecule, and to an ethanol molecule.

PMID- 9757091
TI  - Structures of monoclinic lysozyme iodide at 1.6 A and of triclinic lysozyme
      nitrate at 1.1 A.
AB  - Hen egg-white lysozyme is one of the most thoroughly studied of enzymes and has
      been the subject of study by many methods, including X-ray crystallography. The
      present work extends the X-ray crystallography to higher resolution, includes the
      positions of the anions, and examines the contacts of the neighbors in greater
      detail. Data were collected at room temperature on a Rigaku R-axis area detector
      with rotating-anode X-ray generator to 1.6 A resolution for monoclinic lysozyme
      iodide at pH 4.0, to 1.8 A for monoclinic lysozyme iodide at pH 8.0, and to 1.1 A
      resolution for triclinic lysozyme nitrate at pH 4.5. The structures have been
      refined by SHELX93 with the expected number of anion sites being accounted for.
      Two regions of the protein have been found to be variable: residues 65-75 and 99
      104. Except for 65-75 and 99-104, lysozyme is a very stable molecule with the
      crystal forms being held together by the electrostatic contacts of the anions and
      by layers of water molecules. The anion positions can be described as paired half
      sites, each half being contributed by a different lysozyme molecule. The many
      different crystal forms of lysozyme may be due to different combinations of the
      many such half sites on the surface. A hypothesis is presented for lysozyme in
      the different crystal forms and which may be extended to behavior in solution.
      Suggestions for future crystallographic research are proposed, involving anions
      of different shape and charge.

PMID- 9757092
TI  - Structure of a non-psychrophilic trypsin from a cold-adapted fish species.
AB  - The crystal structure of cationic trypsin (CST) from the Atlantic salmon (Salmo
      salar) has been refined at 1.70 A resolution. The crystals are orthorhombic,
      belong to space group P212121, with lattice parameters a = 65.91, b = 83.11 and c
      = 154.79 A, and comprise four molecules per asymmetric unit. The structure was
      solved by molecular replacement with AMoRe and refined with X-PLOR to an R value
      of 17.4% and Rfree of 21.5% for reflections |F| > 3sigmaF between 8.0 and 1.7 A
      resolution. The four non-crystallographic symmetry (NCS) related molecules in the
      asymmetric unit display r.m.s. deviations in the range 0.31-0.74 A for main-chain
      atoms, with the largest differences confined to two loops. One of these is the
      calcium-binding loop where the electron-density indicates a calcium ion for only
      one of the four molecules. In order to find structural rationalizations for the
      observed difference in thermostability and catalytic efficiency of CST, anionic
      salmon trypsin (AST) and bovine trypsin (BT), the three structures have been
      extensively compared. The largest deviations for the superimposed structures
      occur in the surface loops and particularly in the so-called 'autolysis loop'.
      Both the salmon enzymes possess a high methionine content, lower overall
      hydrophobicity and enhanced surface hydrophilicity, compared with BT. These
      properties have so far been correlated to cold-adaptation features, while in this
      work it is shown that the non-psychrophilic cationic salmon trypsin shares these
      features with the psychrophilic anionic salmon trypsin.

PMID- 9757093
TI  - The use of SnB to determine an anomalous scattering substructure.
AB  - The positions of eight Se atoms in a selenomethionyl 35 kDa protein were
      determined at 2.0 and 2.5 A resolution using the direct-methods program SnB. Data
      at the selenium peak, edge and remote wavelengths were measured and processed
      independently. Anomalous difference E magnitudes at each wavelength were derived
      by two different procedures: renormalized diffE values were calculated according
      to the equation diffE = ?sigma[(f + f')2 + f"2]||E+|-|E-||?1/2/2q(sigma f"2)1/2,
      where q is a least-squares fitted renormalization function of sinstraight
      theta/lambda such that <diffE2> = 1.0; and difference E magnitudes were
      calculated from DeltaF2. Locally normalized E magnitudes corresponding to |FA|
      were also derived from the combination of the data at all three wavelengths
      through the use of the MADSYS program suite. Each of the independent sets of
      anomalous difference E magnitudes was capable of producing the correct solution,
      as did the E data obtained from the FA data. Higher success rates with SnB were
      observed for the 2.0 A peak and edge diffE data.

PMID- 9757094
TI  - Structure of bacteriophage T4 fibritin M: a troublesome packing arrangement.
AB  - Fibritin, a 52 kDa product of bacteriophage T4 gene wac, forms 530 A long fibers,
      named whiskers, that attach to the phage neck and perform a helper function
      during phage assembly. Fibritin is a homotrimer, with its predominant central
      domain consisting of 12 consecutive alpha-helical coiled-coil segments linked
      together by loops. The central domain is flanked by small globular domains at
      both ends. Fibritin M is a genetically engineered fragment of the wild type and
      contains 74 amino-acid residues corresponding to the last coiled-coil segment and
      the complete carboxy-terminal domain. The crystals of fibritin M belong to the
      rare space group P3 with three crystallographically independent trimers in the
      unit cell. The structure has been established at 1.85 A resolution by combining
      molecular and isomorphous replacement techniques. One of the two heavy-atom
      derivatives used was gaseous xenon. A substantial fraction of residues in each
      independent trimer is disordered to various extents in proportion to the lack of
      restraints on the molecules provided by the lattice contacts. Accurate modeling
      of the solvent present in the crystals was crucial for achieving good agreement
      with experimental data.

PMID- 9757095
TI  - On the use of strong Patterson function signals in many-body molecular
      replacement.
AB  - The symmetry elements detected by the self-rotation and the Patterson functions,
      associated to strong correlations between the positions of the molecules in the
      asymmetric unit, are used to reduce the effective number of independent bodies to
      be located by the molecular replacement method. A distinction is made between
      'frustrated' crystallographic symmetries, i.e. those that are almost
      crystallographic ones, and 'standard' non-crystallographic symmetries, which are
      taken into account by specific techniques. These have been successfully applied
      to many-body macromolecular crystal structures, with important savings in time
      and computational effort.

PMID- 9757097
TI  - STEP--a trial-and-error procedure for crystal structure determination. II. The
      determination of two small protein structures.
AB  - This paper describes the difficulties in the process of using the trial-and-error
      SYSTEM90 program to determine ab initio the structures of two small proteins App
      [Woolfson & Yao (1990). Acta Cryst. A46, 409-413] and rubredoxin [Sheldrick et
      al. (1993). Acta Cryst. D49, 18-23] with high-resolution data. Some strategies
      for overcoming the difficulties are discussed and the upgraded SYSTEM95 program
      was used successfully to determine the two structures. The most characteristic
      feature of this structure-determination process is that the two proteins are
      treated as unknown structures with only their chemical compositions and high
      resolution data sets known. A new figure of merit R(sc), replacing the old figure
      of merit, XDFOM, is quite effective in picking out a good set of phases in the
      multi-solution stage when the phases are overconsistent. Controlling the Fourier
      recycling technique and the residuals can separate the mixture of structures and
      the enantiomorph and finally give one absolute structure. The results are
      compared with known structures to verify their reliability.

PMID- 9757096
TI  - Detection and use of pseudo-translation in determination of protein structures.
AB  - Two types of pseudo-translation symmetry, pseudo-twofold translational symmetry
      and pseudo-body-centered symmetry, have been found in protein crystals of
      chorismate mutase and cyclophilin C. Statistics on diffraction intensity from
      these two crystals showed that the presence of pseudo-translations in atomic
      space yielded a distribution of systematically strong and weak reflections at low
      resolution. The diffraction pattern resulting from pseudo-translational symmetry
      was apparently similar to that from true crystallographic symmetry at 4 A
      resolution, but was distinct at high resolution. Pseudo-translation can be
      detected by comparing the average magnitudes of certain parity groups of
      reflections in three-dimensional hkl space. Based on the structures of chorismate
      mutase and cyclophilin C, the ratio of >1.2 for the average magnitudes of parity
      groups is sufficient to indicate the existence of pseudo-translation. Although
      pseudo-translation often makes structure determination more difficult, the
      additional information of pseudo-translation has been used successfully in the
      structure determination of chorismate mutase by multiple isomorphous replacement
      and of cyclophilin C by molecular replacement. Thus, examination of pseudo
      translation is recommended at an early stage of structure determination.

PMID- 9757098
TI  - X-ray structure of human lysozyme labelled with 2',3'-epoxypropyl beta-glycoside
      of man-beta1,4-GlcNAc. Structural change and recognition specificity at subsite
      B.
AB  - Human lysozyme (HL) labelled with the 2',3'-epoxypropyl beta-glycoside of Man
      beta1,4-GlcNAc was crystallized at pH 4.5. The cell dimensions were a = 36.39, b
      = 116.38, c = 30.91 A and the space group was P212121. The unit cell contained
      four molecules (Vm = 2.18 A3 Da-1). The crystal structure was determined by
      molecular replacement and refined to an R value of 0.168 for 7060 reflections
      [|Fo| > 3sigma(F)] in the resolution range 8.0-2.1 A. A prominent shift of the
      Calpha-atom positions by up to 3.8 A in the region of residues 45-50 was observed
      compared with wild-type HL. Owing to the conformational change in this region the
      intermolecular contacts were altered remarkably compared to wild-type HL,
      explaining the difference in molecular packing. The Man-beta1,4-GlcNAc moiety
      occupied subsites B and C in the substrate-binding site of HL. Several
      differences in the hydrogen-bonded contacts between the ligand part and the
      protein part were observed for HL labelled with the 2',3'-epoxypropyl beta
      glycoside of Man-beta1,4-GlcNAc compared with HL labelled with the corresponding
      derivatives of GlcNAc-beta1, 4-GlcNAc and Gal-beta1,4-GlcNAc. In contrast to the
      replacement of GlcNAc with Gal, the replacement of GlcNAc with Man did not
      sacrifice the stacking interactions with the side-chain group of Tyr63 as
      determined by the parallelism of the apolar face of the carbohydrate residue and
      the aromatic plane of the Tyr63 side chain. The 2',3'-epoxypropyl beta-glycoside
      of Man-beta1,4-GlcNAc exhibited almost the same affinity towards HL as Gal
      beta1,4-GlcNAc, a much lower affinity than that of GlcNAc-beta1,4-GlcNAc. The
      difference in the protein-ligand interactions was discussed in relation to the
      carbo-hydrate-residue recognition specificity at subsite B of HL. The results
      suggested that Gln104 was a determinant for the strong recognition of GlcNAc
      residue at subsite B in HL.

PMID- 9757099
TI  - Quaternary structure of UEA-II, the chitobiose specific lectin from gorse.
AB  - The chitobiose specific Ulex europaeus lectin II crystallizes in space group
      P3221 with unit-cell dimensions a = b = 105.54, c = 176.26 A. The asymmetric unit
      contains a complete lectin tetramer. The crystals were shown to diffract to 4.5 A
      on a rotating-anode source and to 2.7 A at the Daresbury synchrotron source.
      Molecular replacement and subsequent rigid-body refinement using data to 4.5 A
      yielded a solution corresponding to a tetramer very similar to that of
      phytohemagglutinin-L and soybean agglutinin. The monomers in the Ulex lectin
      tetramer are rotated approximately 5 degrees compared with the phytohemagglutinin
      L and soybean agglutinin structures.

PMID- 9757100
TI  - A description of imperfections in protein crystals.
AB  - An analysis is given of the contribution of various crystal imperfections to the
      rocking widths of reflections and the divergence of the diffracted beams. The
      crystal imperfections are the angular spread of the mosaic blocks in the crystal,
      the size of the mosaic blocks and the variation in cell dimensions between
      blocks. The analysis has implications for improving crystal perfection, defining
      data-collection requirements and for data-processing procedures. Measurements on
      crystals of tetragonal lysozyme at room temperature and 100 K were made in order
      to illustrate how parameters describing the crystal imperfections can be
      obtained. At 100 K, the dominant imperfection appeared to be a variation in unit
      cell dimensions in the crystal.

PMID- 9757101
TI  - Structure of glucoamylase from Saccharomycopsis fibuligera at 1.7 A resolution.
AB  - The yeast Saccharomycopsis fibuligera produces a glucoamylase which belongs to
      sequence family 15 of glycosyl hydrolases. The structure of the non-glycosyl-ated
      recombinant enzyme has been determined by molecular replacement and refined
      against 1.7 A resolution synchrotron data to an R factor of 14.6%. This is the
      first report of the three-dimensional structure of a yeast family 15
      glucoamylase. The refinement from the initial molecular-replacement model was not
      straightforward. It involved the use of an unrestrained automated refinement
      procedure (uARP) in combination with the maximum-likelihood refinement program
      REFMAC. The enzyme consists of 492 amino-acid residues and has 14 alpha-helices,
      12 of which form an (alpha/alpha)6 barrel. It contains a single catalytic domain
      but no starch-binding domain. The fold of the molecule and the active site are
      compared to the known structure of the catalytic domain of a fungal family 15
      glucoamylase and are shown to be closely similar. The active- and specificity
      site residues are especially highly conserved. The model of the acarbose
      inhibitor from the analysis of the fungal enzyme fits tightly into the present
      structure. The active-site topology is a pocket and hydrolysis proceeds with
      inversion of the configuration at the anomeric carbon. The enzyme acts as an exo
      glycosyl hydrolase. There is a Tris [2-amino-2-(hydroxymethyl)-1,3-propanediol]
      molecule acting as an inhibitor in the active-site pocket.

PMID- 9757103
TI  - Accessing lysozyme nucleation with a novel dynamic light scattering detector.
AB  - Dynamic light scattering was employed to investigate the behaviour of nucleating
      hen egg-white lysozyme solutions. For these studies we employed a novel fiber
      optic based microprobe that suppresses multiple light scattering and
      contributions from large clusters in the spectra by backscattering detection. The
      time evolution of small lysozyme clusters is found to obey classical nucleation
      at the initial stages of the reaction.

PMID- 9757102
TI  - Nucleation in protein crystallization.
AB  - In this paper protein crystallization is regarded as a process starting with
      phase separation in a two-component system. The nucleation time of a lysozyme
      solution is measured by recording the NMR spectra of crystallizing solutions as a
      function of time. It is found that there is an appreciable induction time before
      the first nuclei appear in the solution and that this induction time depends
      strongly on the degree of supersaturation due to the protein concentration at a
      given ionic strength or due to the temperature. From the experimental data it is
      evident that (at least for lysozyme) crystallization under the prevailing
      experimental conditions is a transient process with an induction time and not a
      steady-state process.

PMID- 9757104
TI  - Structure determination of the phiX174 closed procapsid.
AB  - The structure of a procapsid of the single-stranded DNA bacteriophage ++phiX174
      was determined to 3.5 A resolution. The crystal space group was I213 with a unit
      cell length of 774 A. The unit cell contained 16 icosahedral virus particles,
      each situated on a crystallographic threefold axis. Thus, there are two
      independent one-thirds of a particle per asymmetric unit, and a total of 40-fold
      non-crystallographic redundancy. To aid in the interpretation of the packing
      arrangement, crystals were prepared for thin sectioning and analyzed by electron
      microscopy. Oscillation X-ray diffraction data was collected on image plates
      using synchrotron radiation and oscillation angles of either 0.25 or 0.30
      degrees. A low-resolution 6.5 A data set collected from a single frozen crystal
      was particularly helpful in the structure determination, because of its
      completeness and internal consistency. The initial particle orientations were
      determined using self-rotation functions, while the initial position of one
      particle was determined from a Patterson map. The structure was solved by
      molecular replacement real-space averaging using a model based on a cryo-electron
      microscopy reconstruction as a starting point for the phase determination. The
      initial structure determination used the data between 20 and 13 A resolution,
      which was then extended one reciprocal lattice point at a time to 6.5 A
      resolution. At this point, a 3.5 A resolution data set compiled from a number of
      crystals collected at 277 K was introduced. Phase extension and averaging
      continued to 3.5 A resolution after re-determining the particle positions and
      orientations. The amino-acid sequences of most of the D, F and G proteins and
      part of the B protein could be unambiguously built into the 3.5 A electron
      density map. Partial crystallographic refinement yielded an R factor of 31.6%,
      consistent with the relatively low resolution and lack of completeness of the
      data.

PMID- 9757105
TI  - Structure of ubiquitin-conjugating enzyme 9 displays significant differences with
      other ubiquitin-conjugating enzymes which may reflect its specificity for sumo
      rather than ubiquitin.
AB  - The three-dimensional structure of ubiquitin-conjugating enzyme 9 (Ubc9) has been
      obtained to a resolution of 2.8 A by molecular replacement followed by a
      combination of automated refinement and graphical intervention. Diffraction data
      were recorded on a single crystal in space group P43 with cell dimensions a = b =
      73.9, c = 42. 9 A. The final model has an R factor of 21.3% for all data to 2.8
      A. Only the N-terminal methionine, a two-residue N-terminal extension and a four
      residue loop are not located by the final electron-density map. Ubc9 is now known
      to be the first sumo, a new ubiquitin-like protein, conjugating enzyme and does
      not conjugate ubiquitin. The structure of Ubc9 shows important differences
      compared with the structures of known ubiquitin-conjugating enzymes. At the N
      terminal helix, the structural and sequence alignments are out of register by one
      amino acid giving Ubc9 a different recognition surface compared to ubiquitin
      conjugating enzymes. This is coupled to a profound change in the electrostatic
      surface of the molecular face remote from the catalytic site. These differences
      may be important in recognition of other proteins in the Sumo conjugation
      pathway. The catalytic cysteine in Ubc9 has a positively charged lip and a
      negatively charged ridge nearby. Both these features seem confined to sumo
      conjugating enzymes, and a sequence alignment of sumo and ubiquitin suggests how
      these might play a role in sumo/ubiquitin discrimination.

PMID- 9757106
TI  - Locations of bromide ions in tetragonal lysozyme crystals.
AB  - Anions have been shown to play a dominant role in the crystallization of chicken
      egg-white lysozyme from salt solutions. Previous studies employing X-ray
      crystallography have found one chloride ion binding site in the tetragonal
      crystal form of the protein and four nitrate ion binding sites in the monoclinic
      form. In this study the anion positions in the tetragonal form were determined
      from the difference Fourier map obtained from lysozyme crystals grown in bromide
      and chloride solutions. Five possible anion-binding sites were found in this
      manner. Some of these sites were in pockets containing basic residues while
      others were near neutral, but polar, residues. The sole chloride ion binding site
      found in previous studies was confirmed, while four further sites were found
      which corresponded to the four binding sites found for nitrate ions in monoclinic
      crystals. The study suggests that most of the anion-binding sites in lysozyme
      remain unchanged even when different anions and different crystal forms of
      lysozyme are employed.

PMID- 9757107
TI  - Crystallography & NMR system: A new software suite for macromolecular structure
      determination.
AB  - A new software suite, called Crystallography & NMR System (CNS), has been
      developed for macromolecular structure determination by X-ray crystallography or
      solution nuclear magnetic resonance (NMR) spectroscopy. In contrast to existing
      structure-determination programs, the architecture of CNS is highly flexible,
      allowing for extension to other structure-determination methods, such as electron
      microscopy and solid-state NMR spectroscopy. CNS has a hierarchical structure: a
      high-level hypertext markup language (HTML) user interface, task-oriented user
      input files, module files, a symbolic structure-determination language (CNS
      language), and low-level source code. Each layer is accessible to the user. The
      novice user may just use the HTML interface, while the more advanced user may use
      any of the other layers. The source code will be distributed, thus source-code
      modification is possible. The CNS language is sufficiently powerful and flexible
      that many new algorithms can be easily implemented in the CNS language without
      changes to the source code. The CNS language allows the user to perform
      operations on data structures, such as structure factors, electron-density maps,
      and atomic properties. The power of the CNS language has been demonstrated by the
      implementation of a comprehensive set of crystallographic procedures for phasing,
      density modification and refinement. User-friendly task-oriented input files are
      available for nearly all aspects of macromolecular structure determination by X
      ray crystallography and solution NMR.

PMID- 9757108
TI  - X-ray topographic studies of protein crystal perfection and growth.
AB  - The effects of solution variations during growth on the perfection of tetragonal
      lysozyme crystals have been characterized using X-ray topography and high angular
      and wavevector resolution reciprocal-space scans. X-ray images of crystals grown
      under nearly uniform conditions show little contrast or evidence of defects, and
      mosaic widths of these crystals are comparable with those reported for
      microgravity-grown crystals. Images of crystals for which solution conditions
      (temperature, pH or salt concentration) are changed after an initial period of
      uniform growth can show extensive contrast, indicating the presence of disorder.
      The X-ray mosaic widths of these crystals can be significantly broadened, but
      their radial widths are at most very slightly broadened, indicating that image
      contrast is primarily due to mosaicity. Comparison of X-ray images with mosaic
      scans indicates that regions grown after the change in solution conditions have
      broader mosaicities and are more disordered; that regions grown immediately after
      the change tend to have broader mosaicities than subsequent growth regions; and
      that the pre-change growth region is largely unaffected by solution changes. The
      observed disorder may arise from solution change-related transient growth
      instabilities, from transient liquid-liquid phase separation that can occur
      during the change, and from post-change relaxation of the lattice constant of the
      pre-change growth regions. These results suggest that solution variations during
      growth, including those typical of macroseeding, vapor-diffusion growth and other
      widely used techniques, may be an important source of disorder in some protein
      crystals.

PMID- 9757109
TI  - Continuous and discontinuous changes in the unit cell of HIV-1 reverse
      transcriptase crystals on dehydration.
AB  - A crystal form of HIV-1 reverse transcriptase (RT) complexed with inhibitors
      showed diffraction to a high-resolution limit of 3.7 A. Instability in the unit
      cell dimensions of these crystals was observed during soaking experiments, but
      the range of this variability and consequent change in lattice order was revealed
      by a chance observation of dehydration. Deliberately induced dehydration results
      in crystals having a variety of unit cells, the best-ordered of which show
      diffraction to a minimum Bragg spacing of 2.2 A. In order to understand the
      molecular basis for this phenomenon, the initial observation of dehydration, the
      data sets from dehydrated crystals, the crystal packing and the domain
      conformation of RT are analysed in detail here. This analysis reveals that the
      crystals undergo remarkable changes following a variety of possible dehydration
      pathways: some changes occur gradually whilst others are abrupt and require
      significant domain rearrangements. Comparison of domain arrangements in different
      crystal forms gives insight into the flexibility of RT which, in turn, may
      reflect the internal motions allowing this therapeutically important enzyme to
      fulfill its biological function.

PMID- 9757110
TI  - Recognition of RNase Sa by the inhibitor barstar: structure of the complex at 1.7
      A resolution.
AB  - We report the 1.7 A resolution structure of RNase Sa complexed with the
      polypeptide inhibitor barstar. The crystals are in the hexagonal space group P65
      with unit-cell dimensions a = b = 56.9, c = 135.8 A and the asymmetric unit
      contains one molecule of the complex. RNase Sa is an extracellular microbial
      ribonuclease produced by Streptomyces aureofaciens. Barstar is the natural
      inhibitor of barnase, the ribonuclease of Bacillus amyloliquefaciens. It inhibits
      RNase Sa and barnase in a similar manner by steric blocking of the active site.
      The structure of RNase Sa is very similar to that observed in crystals of the
      native enzyme and its complexes with nucleotides. Barstar retains the structure
      found in its complex with barnase. The accessible surface area of protein buried
      in the complex is about 300 A2 smaller and there are fewer hydrogen bonds in the
      enzyme-inhibitor interface in RNase Sa-barstar than in barnase-barstar, providing
      an explanation of the reduced binding affinity in the former. Previous studies of
      barstar complexes have used mutants of the inhibitor and this is the first
      structure which includes wild-type barstar.

PMID- 9757111
TI  - Structure of dimeric and monomeric erabutoxin a refined at 1.5 A resolution.
AB  - Erabutoxin a has been crystallized in its monomeric and dimeric forms. The
      structures were refined at 1.50 and 1.49 A resolution, respectively, using
      synchrotron radiation data. The crystals belong to space group P212121, with cell
      dimensions a = 49.84, b = 46.62, c = 21.22 A for the monomer and a = 55.32, b =
      53.54, c = 40.76 A for the dimer. Using starting models from earlier structure
      determinations, the monomeric structure refined to an R value of 16.7% (8004
      unique reflections, 17.0-1.50 A resolution range), while the dimeric structure
      has been solved by the molecular-replacement method with a final R value of 16.9%
      (19 444 unique reflections, 17.4-1.49 A resolution range). The high-resolution
      electron-density maps clearly revealed significant discrete disorder in the
      proteins and allowed an accurate determination of the solvent structure. For the
      monomer, the side chains of six residues were modelled with alternate conformers
      and 106 sites for water molecules and one site for a sulfate ion were included in
      the final model, whereas for the dimer, 206 sites for water molecules were
      included and both C-terminal residues together with the side chains of 11
      residues adopted alternative conformations. A comparison was made with earlier
      structure determinations. The features of the solvent structure of the erabutoxin
      molecules are discussed in detail.

PMID- 9757112
TI  - Crystallization of ccdB.
AB  - CcdB is a small dimeric protein that poisons DNA-topoisomerase II complexes. Its
      crystallization properties in terms of precipitant type, precipitant
      concentration, pH and protein concentration have been investigated leading to a
      novel crystal form which, in contrast to previously reported crystals, is
      suitable for structure determination using the multiple isomorphous replacement
      (MIR) method. The space group of this new form is C2, with unit-cell parameters a
      = 74.94, b = 36.24, c = 35.77 A, beta = 115.27 degrees. The asymmetric unit
      contains a single monomer. Flash-frozen crystals diffract to at least 1.5 A
      resolution, while room-temperature diffraction can be observed up to 1.6 A. The
      double mutant S74C/G77Q, which acts as a super-killer, crystallizes in space
      group I222 (or I212121) with unit-cell dimensions a = 105.58, b = 105.80, c =
      91.90 A. These crystals diffract to 2.5 A resolution.

PMID- 9757113
TI  - Crystallization and preliminary X-ray analysis of pig E3, lipoamide
      dehydrogenase.
AB  - Pig heart lipoamide dehydrogenase was crystallized by the hanging-drop vapor
      diffusion method. X-ray diffraction patterns show that the hexagonal crystals
      have unit-cell dimensions of a = b = 359. 3, c = 140.5 A. The crystal structure
      has been preliminarily solved by the molecular-replacement method in the space
      group P6322. Three dimeric molecules have been found in the asymmetric unit, one
      of them located on the crystallographic twofold axis.

PMID- 9757114
TI  - Purification, crystallization and preliminary X-ray crystallographic analysis of
      Pyrococcus furiosus DNA polymerase.
AB  - DNA polymerase gene from the hyperthermophilic Archaeon Pyrococcus furiosus has
      been cloned and the protein overexpressed in Escherichia coli to produce an
      active enzyme. The purified protein was crystallized from 0.08 M ammonium
      sulfate, 0.05 M Na-cacodylate, pH 6.5, 0.15%(v/v) NP40, 0.05%(v/v) Tween 20 and
      4.5%(w/v) polyethylene glycol 6000 by the vapour-diffusion method. The
      orthorhombic crystals had unit-cell dimensions of a = 92.5, b = 125.4, c = 192.1
      A; alpha = beta = gamma = 90 degrees. The crystals diffracted beyond 4 A on a
      1.08 A synchrotron radiation source.

PMID- 9757115
TI  - Purification, crystallization and preliminary crystallographic analysis of bovine
      cytosolic brain-type creatine kinase.
AB  - Creatine kinase (E.C. 2.3.7.2) is an important enzyme in energy metabolism which
      catalyzes the reversible transfer of a phosphoryl group between phosphocreatine
      and ADP to give ATP. Large quantities of a brain-type creatine kinase have been
      isolated from bovine photoreceptor cells and crystals suitable for X-ray
      diffraction analysis have been obtained by hanging-drop vapor diffusion. Crystals
      grow as tetragonal bipyramids in space group P43212 with cell dimensions a = b =
      96.49, c = 108.42 A and diffract to at least 2.7 A resolution.

PMID- 9757116
TI  - Crystallization and preliminary X-ray crystallographic studies of the plant
      aspartic proteinase cardosin A.
AB  - The plant aspartic proteinase cardosin A was crystallized using vapour diffusion.
      Crystals belong to the monoclinic space group C2, cell dimensions a = 116.9 (2),
      b = 87.2 (8), c = 81.3 (1) A, beta = 104.4 (4) degrees, and contain two molecules
      in the asymmetric unit related by a non-crystallographic twofold axis.
      Diffraction data were collected at room temperature with radiation from a
      synchrotron source up to 2.85 A resolution. When the crystals were flash cooled
      to 110 K in a nitrogen stream the same resolution limit could also be obtained on
      a rotating-anode source. Recently, synchrotron radiation together with flash
      cooling led to an improvement of the diffraction data to 1.72 A resolution.

PMID- 9757117
TI  - Crystallization and preliminary diffraction analysis of a hyperthermostable DNA
      polymerase from a Thermococcus archaeon.
AB  - The hyperthermostable DNA polymerase from a marine Thermococcus archaeon has been
      crystallized in space group P212121, with unit-cell dimensions a = 94.8, b =
      98.2, c = 112.2 A with one molecule per asymmetric unit. Conditions for data
      collection at 98 K have been identified, and a complete data set was collected to
      2.2 A resolution. Strategies employed here may facilitate crystallization of
      other hyperthermostable proteins. The structure of this enzyme will provide the
      first structural data on the archaeal and hyperthermostable classes of DNA
      polymerases. Sequence homology to human polymerase alpha (polymerase B family)
      may make it a model for studying eukaryotic and viral polymerases and for the
      development of anti-cancer and anti-viral therapeutics.

PMID- 9757118
TI  - Crystallization and preliminary X-ray analysis of Escherichia coli GlnK.
AB  - The trimeric signal-transduction protein GlnK, from Escherichia coli, has been
      over-expressed, purified to homogeneity and crystallized. The crystals belong to
      space group P213 with a = 85.53 A and have two subunits in the asymmetric unit.
      The complex of GlnK with ATP crystallized in space group P63 with a = 57.45 and c
      = 54.79 A. These crystals have a single subunit in the asymmetric unit. High
      quality diffraction data from crystals of GlnK and the GlnK complex have been
      collected to 2.0 A.

PMID- 9757119
TI  - Crystallization and preliminary X-ray crystallographic analysis of the EGF
      receptor ectodomain.
AB  - Crystallization of the hydrophilic ectodomain of the epidermal growth factor
      (EGF) receptor has been accomplished in the presence of the ligand EGF. Two
      different crystal forms have been obtained, one of which was suitable for X-ray
      analysis. The space group of this form has been assigned to P21212 with unit-cell
      dimensions of a = 207.4, b = 113.3 and c = 120.4 A. A native data set has been
      recorded and a heavy-atom search is currently under way. Diffraction from these
      crystals, however, is limited to low resolution and extensive trials to improve
      crystal quality further have all failed. To analyse the molecular shape and
      aggregation of the receptor protein in solution, small-angle X-ray diffraction
      and dynamic light-scattering techniques have been applied. Synchrotron radiation
      in combination with cryo-techniques is essential for data collection because of
      the high solvent content and radiation sensitivity.

PMID- 9757120
TI  - Crystallization and preliminary X-ray diffraction studies of DNA polymerase from
      the thermophilic archaeon Sulfolobus solfataricus.
AB  - The thermophilic and thermostable family B DNA polymerase from the archaeon
      Sulfolobus solfataricus (Mr of about 100 kDa) has been crystallized by the
      hanging-drop vapour-diffusion method at 294 K using ammonium sulfate as
      precipitant. The crystals belong to the monoclinic space group C2 with cell
      dimensions a = 187.4, b = 68.5, c = 125.8 A and beta = 107.8 degrees and diffract
      up to 2.7 A resolution on a rotating-anode X-ray source. Native data have been
      collected at 100 K. A heavy-atom derivative search is in progress.

PMID- 9757121
TI  - Crystallization and preliminary X-ray diffraction analysis of antigen-binding
      fragments which are specific for antigenic conformations of sialic acid
      homopolymers.
AB  - Meningococcal meningitis is a severe childhood disease which often results in
      significant disability or death. Two major etiological agents of meningitis are
      the group B meningococci and capsular type K1 E. coli. The virulence of these
      organisms is attributable to structural mimicry between their common alpha(2-8)
      polysialic acid capsular polysaccharide and human tissue antigens, which allows
      the bacteria to evade immune surveillance. There is currently no effective
      vaccine to protect against this infection. It has been demonstrated that the
      capsular polysaccharide of the bacteria can adopt a unique 'antigenic
      conformation'. This antigenic conformation has formed the basis for the
      development of an N-propionylated polysialic acid vaccine. Immunization trials in
      mice with this vaccine show the production of two groups of antibodies, of which
      only N-propionylated polysialic acid-specific were protective. Knowledge of the
      structure of the antigen-binding site which recognizes the protective epitope is
      essential to determining the antigenic conformation of the polysaccharides, and
      is a critical aspect in understanding and improving the action of potential
      vaccines. The antigen-binding fragments (Fab) of one protective (13D9) and one
      non-protective (6B9) monoclonal antibody specific for the capsular
      polysaccharides of group B meningococci have been crystallized and have undergone
      preliminary X-ray diffraction analysis. Both crystals are observed to scatter X
      rays to approximately 1.7 A resolution at the A1 station at the Cornell High
      Energy Synchrotron Source. 13D9 has an orthorhombic unit cell with a = 41.8, b =
      102.3, c = 134.7 A, with space group P212121. Fab 6B9 has an orthorhombic unit
      cell with a = 89.6, b = 132.0 and c = 36.9 A, with space group P21212.

PMID- 9757122
TI  - Crystallization and preliminary X-ray crystallographic studies of the 13-fold
      symmetric portal protein of bacteriophage SPP1.
AB  - Portal proteins are cyclical oligomers which play essential roles in
      bacteriophage pro-capsid formation, DNA packaging, and in connector formation.
      Bacteriophage SPP1 portal protein (gp6) is a turbine-like molecule with 13-fold
      symmetry [Dube et al. (1993) EMBO J. 12, 1303-1309]. The purified protein was
      crystallized with polyethylene glycol 400 as the precipitating agent using the
      vapor-diffusion method. Salt conditions were selected based on the properties of
      gp6 in different ionic environments. X-ray diffraction data up to a resolution of
      7.85 A were measured from frozen crystals with orthorhombic space group C2221 and
      cell dimensions a = 180.5 (5), b = 223.5 (5), c = 417 (1) A. The asymmetric unit
      contains one tridecameric portal protein with 57.3 kDa subunits. The self
      rotation searches confirm the 13-fold symmetry of the crystallized protein.

PMID- 9757123
TI  - Preliminary crystallographic studies of citrate synthase from an Antarctic
      psychrotolerant bacterium.
AB  - Recombinant citrate synthase from a psychrotolerant bacterium, DS2-3R, recently
      isolated in Antarctica, has been crystallized. The crystals belong to space group
      P6122 or P6522, with cell dimensions a = b = 70.8, c = 307.8 A. Diffraction data
      collected on a synchrotron from a cryoprotected crystal extends to at least 2.0
      A. Knowledge of the structure of this enzyme will add to the understanding of
      cold activity and thermolability, and will be of biotechnological interest.
      Previously, the structure of citrate synthase from Archaea inhabiting
      environments at 328 and 373 K, has been reported. This present study will extend
      our understanding of the structural integrity and activity of proteins at the
      temperature extremes of life.

PMID- 9757124
TI  - Crystallographic characterization of Pap1-DNA complex.
AB  - Pap1 is a fission yeast transcription factor that activates genes related with
      resistance against staurosporine, a potent inhibitor of protein kinase C, and has
      been shown to be involved in cell growth, cell cycle, carcinogenesis and
      differentiation. Pap1 has the bZIP DNA-binding domain but binds to non-consensus
      DNA sequences for the bZIP motif. Highly ordered crystals of the DNA-binding
      domain complexed with a DNA fragment that has an ATF/CREB-like non-consensus
      sequence have been obtained. The crystals grew by the vapor-diffusion technique
      with polyethylene glycol 6000 and belong to space group R3 with a = b = 240.78, c
      = 43.85 A. A 2.0 A resolution data set was collected with a cryo-crystallographic
      technique.

PMID- 9757125
TI  - Crystallization and preliminary X-ray diffraction studies on the water soluble
      form of rat heme oxygenase-1 in complex with heme.
AB  - The water-soluble portion of rat heme oxygenase-1 which lacks 22 hydrophobic
      amino-acid residues at the C-terminus was expressed in E. coli and crystallized
      in the form of a complex with heme by the vapor-diffusion method using
      polyethylene glycol 4000 as the precipitant. The crystals belong to the
      tetragonal space group P41212 or P43212, with unit-cell dimensions of a = b =
      56.7, c = 186. 7 A. The crystal contains one heme-heme oxygenase-1 complex in an
      asymmetric unit and diffracts X-rays beyond 3.0 A resolution with a conventional
      X-ray source.

PMID- 9757126
TI  - Crystallization and preliminary X-ray analysis of the beta-isoform of glutamate
      decarboxylase from Escherichia coli.
AB  - Glutamate decarboxylase (GAD) is a vitamin B6 enzyme which catalyzes the alpha
      decarboxylation of L-glutamate to gamma-aminobutyric acid (GABA). Escherichia
      coli cells coexpress two highly homologous enzyme isoforms, GADalpha and GADbeta.
      Well diffracting crystals of GADbeta were obtained by taking advantage of the
      possibility of expressing each isoform separately. They belong to space group P31
      or P32 with the unit-cell dimensions a = b = 115.6 and c = 206.6 A and contain
      one GAD hexamer in the asymmetric unit. High-resolution synchrotron data were
      collected at 100 K for the native protein and a potential heavy-atom derivative.

PMID- 9757127
TI  - Crystallization of succinylated concanavalin A bound to a synthetic bivalent
      ligand and preliminary structural analysis.
AB  - Crystals have been obtained of succinylated concanavalin A complexed to a novel
      bidentate synthetic ligand. The crystals are the first example of a lectin with a
      synthetic multivalent ligand and the first report of crystallization of
      succinylated concanavalin A. The crystals were obtained by sitting-drop vapour
      diffusion equilibrating with a solution of 20% polyethylene glycol, pH 5, 293. 5
      K. Crystals are orthorhombic, belonging to space group C2221 with unit-cell
      dimensions of a = 99.1, b = 127.4, c = 118.9 A. The asymmetric unit contains a
      dimer, with over 65% of the volume occupied by water. The ligand cross links
      concanavalin A monomers. Succinylated concanavalin A is known to be a dimer in
      solution, yet it is found as the typical concanavalin A tetramer in the crystal.
      The contacts holding together the tetramer appear extensive and suggest that a
      fine balance between dimer and tetramers exists. Data to 2.65 A have been
      collected and the structure determined by the molecular replacement method.

PMID- 9757128
TI  - Crystallization and preliminary X-ray diffraction studies of the heterogeneously
      glycosylated enzyme rhamnogalacturonan acetylesterase from Aspergillus aculeatus.
AB  - Well diffracting crystals of rhamnogalacturonan acetylesterase from Aspergillus
      aculeatus have been obtained in two polymorphic modifications despite its
      heterogeneous glycosylation. The best-diffracting crystals (resolution 1.55 A)
      are orthorhombic. The limit of the diffraction pattern of the other (trigonal)
      form is 2.5 A. The ability of the enzyme to crystallize appears to depend on the
      glycosylation of the protein sample. This aspect has been investigated by mass
      spectrometry, which also showed that the orthorhombic crystals have the same
      glycosylation as the protein sample used in the crystallization.

PMID- 9757129
TI  - Purification, crystallization and preliminary X-ray analysis of human recombinant
      cytosolic serine hydroxymethyltransferase.
AB  - As an enzyme of the thymidylate synthase cycle, serine hydroxymethyltransferase
      (SHMT) has a key role in nucleotide biosynthesis. Elevated activities of SHMT
      have been correlated with the increased demand for nucleotide biosynthesis in
      tumors of human and rodent origin, making this enzyme a novel target for cancer
      chemotherapy. Here the purification and crystallization of recombinant human
      cytosolic SHMT are reported. Crystals belong to space group P6222 or P6422 with
      cell parameters a = b = 155.0, c = 235.5 A and diffract to at least 3.0 A
      resolution.

PMID- 9757130
TI  - Crystallization and preliminary X-ray characterization of aspartate
      aminotransferase from an extreme thermophile, Thermus thermophilus HB8.
AB  - Recombinant aspartate aminotransferase from an extremely thermophilic bacterium,
      Thermus thermophilus HB8, has been crystallized in two different crystal forms.
      The crystals of both forms are orthorhombic and belong to space group P212121
      with cell dimensions a = 124.3, b = 113.6 and c = 61.6 A for form I and a =
      197.3, b = 109.7 and c = 80.3 A for form II. The crystals of form I and II
      diffract to 2.1 and 2.5 A resolution, respectively, on a conventional laboratory
      rotating-anode source. Two heavy-atom derivatives have been identified for form
      I.

PMID- 9757131
TI  - Crystallization and preliminary X-ray diffraction studies of the oxygenating
      subunit of 3,6-diketocamphane monooxygenase from Pseudomonas putida.
AB  - The oxygenating constituent of the 3,6-diketocamphane monooxygenase isozyme from
      Pseudomonas putida NCIMB 10007 has been crystallized under two different
      conditions. Crystals were initially grown from polyethylene glycol (PEG) 8000 and
      sodium acetate using the vapour-phase diffusion method. The crystals were of
      orthorhombic P212121 space group, with cell dimensions a = 55.8, b = 94.5 and c =
      163.7 A and diffracted to 2.8 A resolution. More recently, improved crystals,
      which diffracted beyond 2 A, have been grown from ammonium sulfate. These
      crystals also belong to the orthorhombic P212121 space group, with cell
      dimensions of a = 54.6, b = 93.2 and c = 154. 1 A. A full native data set to 2.5
      A resolution has been collected from the ammonium sulfate grown crystals.

PMID- 9757132
TI  - Crystallization and preliminary X-ray analysis of recombinant glutamate mutase
      and of the isolated component S from Clostridium cochlearium.
AB  - Glutamate mutase [varepsilon2sigma2(B12)1] was reconstituted by incubating
      purified components E (varepsilon2) and S (sigma2) from Clostridium cochlearium,
      both produced in Escherichia coli, with either aquo- or cyanocobalamin. The
      inactive glutamate mutase obtained was crystallized with polyethyleneglycol 4000
      as precipitant. Crystals are monoclinic with space group P21 and have cell
      dimensions a = 64.6, b = 113.2, c = 108.4 A and beta = 96.0 degrees for the
      glutamate mutase reconstituted with aquocobalamin. They diffract to a resolution
      of at least 2.7 A. Isolated component S was crystallized in the presence of an
      excess of cyanocobalamin, yielding red crystals of space group I422 with unit
      cell dimensions of a = b = 69.9 and c = 107.1 A. The crystals diffract to about
      3.2 A resolution. Native data sets were collected for both crystal forms.

PMID- 9757133
TI  - Cloning, overproduction, purification and crystallization of the DNA binding
      protein HU from the hyperthermophilic eubacterium Thermotoga maritima.
AB  - The humar gene encoding for the histone-like DNA-binding protein HU from the
      hyperthermophilic eubacterium Thermotoga maritima was efficiently overexpressed
      in Escherichia coli under the T7 promoter. The HU protein was purified using SP
      Sepharose ion-exchange and heparin-affinity chromatography and was successfully
      crystallized in ammonium sulfate. The crystals were grown in the tetragonal form
      in space group P43 or P41 and have unit-cell dimensions a = b = 46.12, c = 77.56
      A, alpha = beta = gamma = 90 degrees. The crystals diffract X-rays to 1.6 A
      resolution using synchrotron radiation and are suitable for determination of the
      HU structure at high resolution.

PMID- 9757134
TI  - Expression, purification, crystallization and preliminary X-ray analysis of
      cyclophilin A from the bovine parasite Trypanosoma brucei brucei.
AB  - Cyclophilin A from the bovine parasite Trypanosoma brucei brucei has been cloned,
      expressed in Escherichia coli, purified and crystallized in the presence of
      cyclosporin A using ammonium sulfate as a precipitant. The crystals belong to the
      orthorhombic crystal system with unit-cell dimensions of a = 118.61, b = 210.15
      and c = 153.21 A. A data set complete to 2.7 A has been collected using rotating
      anode radiation, however the crystals diffract to at least 2.1 A resolution using
      synchrotron radiation.

PMID- 9757135
TI  - Structure of pig plasma retinol-binding protein at 1.65 A resolution.
AB  - The crystal structure of pig plasma retinol-binding protein (RBP) has been
      determined at 1.65 A resolution. The space group is P212121, with a = 45.81 (4),
      b = 53.14 (5), c = 72.97 (8) A and one protein molecule in the asymmetric unit.
      The structure has been solved using the molecular replacement method and refined
      with restrained least squares to an R factor of 0.1844 and an Rfree of 0.237 for
      18 874 and 1001 independent reflections, respectively. The relatively high
      resolution structure of pig holoRBP has revealed some new structural details.
      Moreover, it has provided a description of the binding site for Cd2+, a metal ion
      which is required for protein crystallization. The hepta-coordination of the RBP
      bound cadmium ion involves different residues of two symmetry-related RBP
      molecules, consistent with the participation of the cation in intermolecular
      interactions that in turn promote protein crystallization.

PMID- 9757136
TI  - Rapid X-ray diffraction analysis of HIV-1 protease-inhibitor complexes: inhibitor
      exchange in single crystals of the bound enzyme.
AB  - The ability to replace an inhibitor bound to the HIV-1 protease in single
      crystals with other potent inhibitors offers the possibility of investigating a
      series of protease inhibitors rapidly and conveniently with the use of X-ray
      crystallography. This approach affords a fast turnaround of structural
      information for iterative rational drug designs and obviates the need for
      studying the complex structures by co-crystallization. The replacement approach
      has been successfully used with single crystals of the HIV-1 protease complexed
      with a weak inhibitor. The structures of the complexes obtained by the
      replacement method are similar to those determined by co-crystallization.

PMID- 9757137
TI  - Crystallization and preliminary X-ray studies of purine nucleoside phosphorylase
      from Cellulomonas sp.
AB  - The commercially available enzyme purine nucleoside phosphorylase (PNP) from
      Cellulomonas sp. was purified by ion--exchange chromatography, partially
      sequenced and crystallized in two different crystal forms using the hanging-drop
      vapour-diffusion technique. Crystal form A grows as polyeders and/or cubes in the
      cubic space group P4232 with unit-cell dimension a = 162.5 A. Crystal form B
      appears as thick plates in the space group P212121 with unit-cell dimensions a =
      63.2, b = 108.3 and c = 117.4 A. Both crystal forms contain three monomers (one
      trimer) in the asymmetric unit.

PMID- 9757138
TI  - Intra- and intercellular Ca2+ signaling in paraneurons and other secretory cells.
AB  - Paraneurons are endocrine and sensory cells which share structural, functional,
      and metabolic features with neurons. They produce identical with or related to
      neurotransmitters or neurohormones, which are synthesized and secreted by
      regulated secretion. They are receptoconductile-secretory in function, which is
      shared by specific proteins distributed at proper regions of cell membrane. A
      substantial advance has been made in the molecular machinery underlying protein
      sorting and transport within the endoplasmic reticulum and Golgi apparatus, and
      the mechanism of targeted membrane fusion by constitutive secretion. Various
      patterns of [Ca2+]c dynamics play cardinal signaling roles in stimulus-secretion
      coupling in individual secretory cells. Long-lived recurrent Ca2+ spikes or
      oscillation may maintain prolonged secretory responses, ATP synthesis in
      mitochondria, cell growth, differentiation, and division. In the neurons and the
      paraneurons of neuroectodermal origin, action potentials propagate along a
      conductile region to the secretory region of each cell and hardly be transmitted
      to the adjacent cells. In the paraneurons of gut endodermal origin, intracellular
      signalling including Ca2+ spikes can be propagated to the adjacent cells, and in
      turn may maintain coordination of individual cells forming a cell society.

PMID- 9757139
TI  - Adaptive changes in the capillary network in the left ventricle of rat heart.
AB  - Capillaries are nonuniform thin tubes: The arteriolar and venular capillary
      portions express alkaline phosphatase (AP) and dipeptidyl peptidase IV (DPPIV),
      respectively. Differences in enzyme activities between arteriolar and venular
      capillary portions could be shown by staining sections of cardiac tissues for AP
      and DPPIV after coronary infusion of microspheres and by staining cultured
      endothelial cells that had been collected from coronary microvessels. Through use
      of a double staining method for AP and DPPIV, adaptive changes in the capillary
      network were studied in rat hearts exposed to cold, exercise, hypertension,
      chronic coronary occlusion, and transient coronary occlusion followed by
      reperfusion. Two patterns could be seen in the adaptations of the ventricular
      capillary network. The increase in the venular capillary portions is accompanied
      by remarkable increases in capillary density and capillary-to-myocyte ratio. The
      increase in the arteriolar capillary portion seemed to be accompanied by a
      decrease or only a limited increase in capillary density in stressed hearts. The
      increase in the total capillary density improves the capacity for oxygen
      transport to tissues with a high tissue perfusion and a short diffusion distance
      for oxygen. The increase in the arteriolar capillaries may also improve oxygen
      transport by increasing the arterial blood perfusing the tissue. This seems,
      however, a compensation for the limited angiogenesis: The alleviation of
      stresses, such as pharmacological treatment of the hypertrophied heart and
      reperfusion after transient ischemia, increases venular capillary portions and
      capillary density. These changes are discussed with immunohistochemical
      observations of rapid and prolonged expressions of angiogenic growth factors.

PMID- 9757140
TI  - Impact of diffusional oxygen transport on oxidative metabolism in the heart.
AB  - The resistance for the oxygen molecule to diffuse from the capillary blood to the
      cell surface produces remarkably large gradients of oxygen partial pressure (PO2)
      in the extracellular space. In addition, the intracellular radial gradients of
      PO2 may not be ignored particularly when the cellular oxygen consumption is
      increased. These PO2 gradients together result in a quite low intracellular PO2
      in the cardiomyocyte in vivo. Thus, the cellular oxidative metabolism may be
      limited by diffusional transport of oxygen from the capillary blood to
      mitochondria. In this review, quantitative aspects and physiological relevances
      of the PO2 gradient in the myocardium are discussed.

PMID- 9757141
TI  - Immediate and sustained effects of smoking on autonomic arousal in human
      subjects.
AB  - The effects of smoking on sudomotor/autonomic activity were examined by measuring
      water transfer across the skin (sweat output) as an index of activity. Sweat
      output was measured in 14 subjects (11 male and 3 female) during the act of
      smoking and for about 60 min following this. Sweat output was measured in 5 (4
      male, 1 female) controls over the same time period. Smoking had two effects on
      sweat output: In 12 subjects it caused an immediate increase in output; in 4 of
      these 12 the increase persisted for the duration of the recording period. In the
      other 2 subjects no increase was noted, but in no subject did smoking cause a
      decrease in sweat output. Mood state questionnaires were administered at the
      beginning and end of the experimental period. No clear association was found
      between scores on the mood questionnaires and the autonomic effects of smoking.
      In 2 subjects, transdermal blood flow was also measured during and after smoking.
      Smoking caused a decrease in blood flow in these subjects. These results are
      discussed in terms of the "arousal modulation" hypothesis of smoking.

PMID- 9757142
TI  - Excitation of baroreceptors depresses A- and C-components of the somato-cardiac
      sympathetic reflex in anesthetized rats.
AB  - The effect of baroreceptor activation on somato-cardiac sympathetic reflex
      discharges was examined in urethane-anesthetized, vagotomized, and artificially
      ventilated rats. Single shock stimulation of myelinated (A) and unmyelinated (C)
      fibers in the tibial nerve of the left hindlimb elicited two separate excitatory
      reflex discharge components in a branch of the cardiac sympathetic nerve. They
      are termed the A- and C-components of the somato-cardiac sympathetic reflex
      discharges. When aortic nerves (AN) and carotid sinus nerves (CSN) were intact, a
      sudden increase in mean arterial blood pressure to about 150 mmHg induced by I.V.
      injection of phenylephrine (50 micro/kg) depressed the A- and C-components by up
      to 47 +/- 5.4 and 37 +/- 7.7% of the control values, respectively. However,
      bilateral sino-aortic denervation completely abolished the pressure-induced
      depression of both components. We conclude that baroreceptor afferent signals
      from the AN and CSN inhibit both A- and C-components of the excitatory somato
      cardiac sympathetic reflex discharges. This and other previous evidence mentioned
      in the text indicate that inhibitory cardiac sympathetic reflexes originating
      from arterial baroreceptors and excitatory ones originating from somatic
      afferents interact, probably at the brainstem.

PMID- 9757143
TI  - Effect of posture change on control of ventilation.
AB  - To clarify the control mechanism of ventilation during posture change,
      ventilatory parameters, PETCO2, and ventilatory response to CO2 were examined in
      11 healthy male subjects at supine (0 degrees) and 75 degrees head-up tilt
      positions. Minute expiratory ventilation (V.E), tidal volume (VT), respiratory
      frequency (f), end-tidal and transcutaneous PCO2 and CO2 output (V.CO2), and
      ventilatory response to CO2 were measured during a steady state condition. V.E
      (V.A) and VT increased significantly at 75 degrees tilt with significant decrease
      in PETCO2 from 40.1 mmHg (0 degrees) to about 36.1 mmHg (75 degrees).
      Transcutaneous PCO2 also decreased during tilt, by 3.3 mmHg. Physiological dead
      space (VD/VT) and V.CO2, however, remained unchanged, and ventilatory equivalent
      (V.E/V.CO2, V.A/V.CO2) increased significantly. The CO2-ventilatory response
      curve shifted upward (or leftward) without significant change in the response
      slope. At 75 degrees tilt, EMG activity of gastro-cnemius muscle increased. These
      findings suggested that PETCO2 decreased because of increased V.E (V.A) with a
      leftward shift of CO2-ventilatory response curve. Various signals such as
      afferents from lower extremities might have net stimulatory effects on a CO2
      ventilation control system to reset the controlled level of PETCO2 to a lower
      range, but without significant change in CO2-ventilatory response during upright
      position.

PMID- 9757144
TI  - Involvement of NMDA and non-NMDA receptors in the neuronal responses of the
      primary motor cortex to input from the supplementary motor area and somatosensory
      cortex: studies of task-performing monkeys.
AB  - The involvement of N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors
      in mediating the excitatory responses of neurons in the primary motor cortex (MI)
      to electrical stimulation of the supplementary motor area (SMA) and the
      somatosensory cortex (SI) was examined in monkeys performing a trained motor
      task. During the task, a total of 109 MI neurons were identified and classified
      as movement related (91), motor set related (7), or mixed (11). Subsequently, the
      influence of receptor antagonists on the stimulus-evoked and task-related
      activities of these neurons was examined. The selective NMDA antagonist D-2-amino
      5-phosphonovaleric acid (APV) and the selective non-NMDA antagonist 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX) were applied iontophoretically through
      multibarreled micropipettes. One barrel was used for extracellular unit
      recording. The excitatory response evoked by SI stimulation was suppressed by
      CNQX in the vast majority (83%) of the motor task related neurons, and only 10%
      were suppressed by APV. On the other hand, the response evoked by SMA stimulation
      was suppressed by APV in 56% of the neurons and by CNQX in 54%. APV and CNQX had
      parallel effects on the stimulus-evoked responses and the task-related neuronal
      activity. These results indicate that NMDA and non-NMDA receptors are both
      involved in mediating the excitatory responses of MI neurons to input from the
      SMA and SI. On the other hand, the data suggest a greater contribution of non
      NMDA receptors in response to SI input and greater involvement of NMDA receptors
      in mediating the response to SMA input, especially among set-related MI neurons.

PMID- 9757145
TI  - Influence of sustained hypoxia on the sensation of dyspnea.
AB  - We assessed the effect of sustained isocapnic hypoxia (PCO2 = 40 Torr, SaO2 =
      80%) on the sensation of dyspnea in 16 normal healthy males. Subjects rated the
      sensation of dyspnea (c) on 15 cm visual analog scales during 20 min of sustained
      hypoxia. Following this hypoxic period, 8 subjects undertook mild exercise (10-50
      W on a bicycle ergometer for 3 min) under the continuation of hypoxia. During
      sustained hypoxia, psi increased initially with ventilation from 0.6 +/- 0.2 (n =
      16, mean +/- SE) to 2.9 +/- 0.6 at peak ventilation, but it decreased with
      ventilatory depression to 1.6 +/- 0.4. Dyspnea intensity during hypoxic exercise
      was significantly smaller than that at peak ventilation in the resting hypoxic
      period (2.3 +/- 0.7 vs. 3.9 +/- 1.0), although the ventilation was greater during
      exercise (24.0 +/- 3.0 vs. 19.7 +/- 1.4 l/min). These results indicate that
      sustained hypoxia has a biphasic, i.e., initial stimulatory and delayed
      depressant, effect on dyspnea and on ventilation. It is suggested that the
      dyspnea sensing mechanism is suppressed during mild exercise under sustained
      hypoxia.

PMID- 9757146
TI  - Repetitive mechanical responses of the amphibian skin to adrenergic stimulation .
AB  - Mechanical responses of the amphibian nerve-skin preparation to adrenergic
      stimulation were investigated by recording pressure changes at the skin surface
      with a piezoelectric sensor. When a dilute epinephrine (or norepinephrine)
      solution was applied to the inner skin surface, repetitive mechanical responses,
      representing quick swelling of the skin repeating at more or less regular
      intervals of about 1 min, were frequently observed. In about 10% of the
      preparations, the skin was found to undergo repetitive quick shrinkage (instead
      of swelling) under practically indistinguishable experimental conditions. Rapid
      volume changes occurring in the cytoplasmic gel of the gland cells are considered
      to be at the base of these repetitive mechanical responses.

PMID- 9757147
TI  - Ketoconazole inhibition of triazolam and alprazolam clearance: differential
      kinetic and dynamic consequences.
AB  - BACKGROUND: Kinetic and dynamic consequences of metabolic inhibition were
      evaluated in a study of the interaction of ketoconazole, a P4503A inhibitor, with
      alprazolam and triazolam, two 3A substrate drugs with different kinetic profiles.
      METHODS: In a double-blind, 5-way crossover study, healthy volunteers received
      (A) ketoconazole placebo plus 1.0 mg alprazolam orally, (B) 200 mg ketoconazole
      twice a day plus 1.0 mg alprazolam, (C) ketoconazole placebo plus 0.25 mg
      triazolam orally, (D) 200 mg ketoconazole twice a day plus 0.25 mg triazolam, and
      (E) 200 mg ketoconazole twice a day plus benzodiazepine placebo. Plasma
      concentrations and pharmacodynamic parameters were measured after each dose.
      RESULTS: For trial B versus trial A, alprazolam clearance was reduced (27 versus
      86 mL/min; P < .002) and apparent elimination half-life (t1/2) prolonged (59
      versus 15 hours; P < .03), whereas peak plasma concentration (Cmax) was only
      slightly increased (16.1 versus 14.7 ng/mL). The 8-hour pharmacodynamic effect
      areas for electroencephalographic (EEG) beta activity were increased by a factor
      of 1.35, and those for digit-symbol substitution test (DSST) decrement were
      increased by 2.29 for trial B versus trial A. For trial D versus trial C,
      triazolam clearance was reduced (40 versus 444 mL/min; P < .002), t1/2 was
      prolonged (18.3 versus 3.0 hours; P < .01), and Cmax was increased (2.6 versus
      5.4 ng/mL; P < .001). The 8-hour effect area for EEG was increased by a factor of
      2.51, and that for DSST decrement was increased by 4.33. Observed in vivo
      clearance decrements due to ketoconazole were consistent with those anticipated
      on the basis of an in vitro model, together with in vivo plasma concentrations of
      ketoconazole. CONCLUSION: For triazolam, an intermediate-extraction compound,
      impaired clearance by ketoconazole has more profound clinical consequences than
      those for alprazolam, a low extraction compound.

PMID- 9757148
TI  - Grapefruit juice-felodipine interaction: effect of naringin and 6',7'
      dihydroxybergamottin in humans.
AB  - OBJECTIVE: To test whether naringin or 6',7'-dihydroxybergamottin is a major
      active substance in grapefruit juice-felodipine interaction in humans. METHODS:
      Grapefruit juice was separated by means of centrifugation and filtration into
      supernatant and particulate fractions, which were then assayed for naringin and
      6',7'-dihydroxybergamottin. The effect of these fractions, grapefruit juice
      (containing comparable amounts of both fractions), and water on the
      pharmacokinetics of oral felodipine were assessed in 12 healthy men in a
      randomized, 4-way crossover study. RESULTS: The amounts of naringin and 6',7'
      dihydroxybergamottin in the supernatant fraction (148 mg and 1.85 mg) were
      greater than in the particulate fraction (7 mg and 0.60 mg). The area under the
      plasma concentration-time curve (AUC) and the peak concentration (Cmax) of
      felodipine were higher with supernatant fraction (81 nmol.h/L and 20 nmol/L),
      particulate fraction (117 nmol.h/L and 24 nmol/L), and grapefruit juice (130
      nmol.h/L and 33 nmol/L) compared with water (53 nmol.h/L and 11 nmol/L). However,
      the supernatant fraction had a lower AUC for felodipine and a similar Cmax of
      felodipine relative to the particulate fraction. The supernatant fraction neither
      augmented the AUC of the primary metabolite dehydrofelodipine nor decreased the
      AUC ratio of dehydrofelodipine to felodipine compared with water. Individually
      the supernatant fraction consistently produced lower felodipine AUC and Cmax
      compared with grapefruit juice. In contrast, the particulate fraction had values
      ranging from more than grapefruit juice to less than supernatant fraction.
      CONCLUSIONS: Naringin and 6',7'-dihydroxybergamottin are not the major active
      ingredients, although they may contribute to the grapefruit juice-felodipine
      interaction. The variable effect with the particulate fraction may result from
      erratic bioavailability of unidentified primary active substances. The findings
      show the importance of in vivo testing to determine the ingredients in grapefruit
      juice responsible for inhibition of cytochrome P450 3A4 in humans.

PMID- 9757149
TI  - Effect of fluvoxamine therapy on the activities of CYP1A2, CYP2D6, and CYP3A as
      determined by phenotyping.
AB  - OBJECTIVE: To determine the effect of 150 mg/day fluvoxamine on the activities of
      CYP1A2, CYP2D6, CYP3A, N-acetyltransferase-2 (NAT2), and xanthine oxidase (XO) by
      phenotyping with caffeine, dextromethorphan, and midazolam. METHODS: Oral
      caffeine (2 mg/kg), oral dextromethorphan (30 mg), and intravenous midazolam
      (0.025 mg/kg) were administered to 10 white male volunteers every 14 days for 4
      months and to 10 white premenopausal female volunteers during the midfollicular
      and midluteal phases of the menstrual cycle for 4 complete cycles (8 total
      phenotyping measures). The first 6 phenotyping measures were used to establish
      baseline activity. Subjects were given 150 mg/day fluvoxamine for the fourth
      month or cycle of the study. Enzyme activity for CYP1A2, CYP2D6, NAT2, and XO was
      expressed as urinary metabolite ratios. Midazolam plasma clearance was used to
      express CYP3A activity. RESULTS: No difference between baseline and weeks 2 and 4
      of fluvoxamine therapy was observed for NAT2 or XO metabolite ratios. For CYP1A2,
      CYP2D6, and CYP3A phenotypes, significant differences existed between baseline
      and fluvoxamine therapy. For CYP1A2, the mean urinary metabolite ratio (+/-SD)
      was 7.53 +/- 7.44 at baseline and 4.30 +/- 2.82 with fluvoxamine ( P = .012).
      Mean CYP2D6 molar urinary dextromethorphan ratios before and after fluvoxamine
      therapy were 0.00780 +/- 0.00694 and 0.0153 +/- 0.0127, respectively (P = .011).
      Midazolam clearance decreased from 0.0081 +/ 0.0024 L/min/kg at baseline to
      0.0054 +/- 0.0021 L/min/kg with therapy (P = .0091). For CYP1A2, CYP2D6, and
      CYP3A, fluvoxamine therapy changed the phenotyping measures by a median of 
      44.4%, 123.5%, and -34.4%, respectively. CONCLUSIONS: We concluded that
      fluvoxamine may cause significant inhibition of CYP1A2, CYP2D6, and CYP3A
      activity. This metabolic inhibition may have serious implications for a variety
      medications.

PMID- 9757150
TI  - Quantification of 3-month intraindividual variability and the influence of sex
      and menstrual cycle phase on CYP3A activity as measured by phenotyping with
      intravenous midazolam.
AB  - OBJECTIVE: Intraindividual variability and the effects of sex and menstrual cycle
      phase on CYP3A activity were evaluated by phenotyping with use of midazolam as
      the probe drug. METHODS: Midazolam (0.025 mg/kg) was administered intravenously
      to 10 white male volunteers every 14 days for 3 months and to 10 white
      premenopausal female volunteers during the midfollicular and midluteal phases of
      the menstrual cycle for 3 complete cycles. Serum was collected for a 6-hour
      period, and enzyme activity was represented by midazolam plasma clearance.
      RESULTS: No difference in clearance was observed during the menstrual cycle
      phases. Mean +/- SD midazolam clearance was 0.00816 +/- 0.00252 L/min/kg during
      the midfollicular phase and 0.00818 +/- 0.00224 during the midluteal phase (P =
      .96). When the menstrual cycle phases were combined, mean midazolam clearance in
      women was 0.00817 +/- 0.00235 L/min/kg. Mean male midazolam clearance was 0.00766
      +/ 0.00167 L/min/kg. There was no difference in midazolam clearance between men
      and women (P = .68). Coefficients of variation (CV%) for the 6 phenotyping visits
      were calculated and the median midazolam clearance CV% (25th to 75th percentile)
      was 9.75% (8.40% to 11.5%). CONCLUSIONS: Because no significant differences in
      midazolam clearance were noted between menstrual cycle phases or between sexes,
      pharmacokinetic and clinical investigations of CYP3A activity in adults may not
      require stratification on the basis of menstrual cycle phase or sex.

PMID- 9757152
TI  - Effect of grapefruit juice on carbamazepine bioavailability in patients with
      epilepsy.
AB  - OBJECTIVE: To examine the effect of grapefruit juice on the bioavailability of
      carbamazepine in patients with epilepsy. METHODS: This was a randomized crossover
      study consisting of 2 phases. Ten patients with epilepsy who had received therapy
      with 200 mg carbamazepine 3 times a day for the previous 3 to 4 weeks
      participated. They were given either grapefruit juice or 300 mL water at 8 am
      along with 200 mg carbamazepine. Each treatment was separated by 2 days; subjects
      continued to receive carbamazepine therapy during the 2-day period. On both
      occasions, blood samples were collected at different time intervals between 0 to
      8 hours. Carbamazepine levels were estimated by reversed-phase HPLC technique.
      RESULTS: Compared with water, grapefruit significantly increased the steady peak
      concentration (6.55 versus 9.20 microgram/mL), trough concentration (4.51 versus
      6.28 microgram/mL), and area under the plasma concentration-time curve (43.99
      versus 61.95 micrograms.h/mL) of carbamazepine. No significant effect was found
      in the time to reach peak plasma concentration. CONCLUSION: Grapefruit juice
      increases the bioavailability of carbamazepine by inhibiting CYP3A4 enzymes in
      gut wall and in the liver.

PMID- 9757151
TI  - Inhibition of triazolam clearance by macrolide antimicrobial agents: in vitro
      correlates and dynamic consequences.
AB  - BACKGROUND: Macrolide antimicrobial agents may impair hepatic clearance of drugs
      metabolized by cytochrome P4503A isoforms. Potential interactions of triazolam, a
      substrate metabolized almost entirely by cytochrome P4503A in humans, with 3
      commonly prescribed macrolides were identified using an in vitro metabolic model.
      The actual interactions, and their pharmacodynamic consequences, were verified in
      a controlled clinical study. METHODS: In an in vitro model using human liver
      microsomes, 250 mumol/L triazolam was incubated with ascending concentrations (0
      to 250 mumol/L of troleandomycin, azithromycin, erythromycin, and clarithromycin.
      In a randomized, double-blind, 5-trial clinical pharmacokinetic-pharmacodynamic
      study, 12 volunteers received 0.125 mg triazolam orally, together with placebo,
      azithromycin, erythromycin, or clarithromycin. In a fifth trial they received
      placebo plus placebo. RESULTS: Mean 50% inhibitory concentrations versus 4
      hydroxytriazolam formation in vitro were as follows: 3.3 mumol/L troleandomycin,
      27.3 mumol/L erythromycin, 25.2 mumol/L clarithromycin, and greater than 250
      mumol/L azithromycin. Apparent oral clearance of triazolam when given with
      placebo or azithromycin was nearly identical (413 and 416 mL/min), as were peak
      plasma concentrations (1.25 and 1.32 ng/mL) and elimination half-life (2.7 and
      2.6 hours). Apparent oral clearance was significantly reduced (P < .05) during
      erythromycin and clarithromycin trials (146 and 95 mL/min). Peak plasma
      concentration was correspondingly increased, and elimination half-life was
      prolonged. The effects of triazolam on dynamic measures were nearly identical
      when triazolam was given with placebo or azithromycin, but benzodiazepine agonist
      effects were enhanced during erythromycin and clarithromycin trials. CONCLUSION:
      The in vitro model identifies macrolides that may impair triazolam clearance.
      Anticipated interactions, and their pharmacodynamic consequences in volunteer
      subjects, were verified in vivo.

PMID- 9757153
TI  - Pharmacokinetics of cyclophosphamide and its metabolites in bone marrow
      transplantation patients.
AB  - OBJECTIVES: To characterize the pharmacokinetics of cyclophosphamide and 5 of its
      metabolites in bone marrow transplant patients and to identify the mechanism of
      the increase in 4-hydroxycyclophosphamide area under the plasma concentration
      time curve (AUC) from day 1 to day 2 of cyclophosphamide administration. METHODS:
      Cyclophosphamide was administered by intravenous infusion (60 mg/kg over 1 hour,
      once a day) for 2 consecutive days to 18 patients. Cyclophosphamide and 4
      hydroxycyclophosphamide concentration time data on day 1 and day 2 were fitted to
      a model to estimate 4-hydroxycyclophosphamide formation (CLf) and elimination
      (CLm) clearances. Erythrocyte aldehyde dehydrogenase-1 activity was measured ex
      vivo just before the first cyclophosphamide infusion was started (0 hours) and 24
      hours after the second cyclophosphamide infusion (48 hours). RESULTS: From day 1
      to day 2, the AUC of cyclophosphamide, deschloroethyl cyclophosphamide and
      phosphoramide mustard decreased 24.8%, 51%, and 29.4% (P < .02), the AUC of 4
      hydroxycyclophosphamide and carboxyethylphosphoramide mustard increased 54.7% and
      25% (P < .01), whereas the AUC of phosphoramide mustard was not significantly
      changed (P > .3). The CLf of 4-hydroxycyclophosphamide increased 60% (P < .001),
      its CLm decreased 27.7% (P < .001), and the fraction of cyclophosphamide dose
      converted to 4-hydroxycyclophosphamide increased 16% (P < .001) from day 1 to day
      2. The activity of patient erythrocyte aldehyde dehydrogenase-1 decreased 23.3%
      (P < .02) from 0 hours to 48 hours. CONCLUSIONS: The AUC of 4
      hydroxycyclophosphamide increased from day 1 to day 2 as a result of increased
      formation and decreased elimination clearances of 4-hydroxycyclophosphamide.
      Aldehyde dehydrogenase-1 activity appears to decline as a consequence of
      cyclophosphamide administration.

PMID- 9757154
TI  - Amiodarone causes endothelium-dependent vasodilation in human hand veins in vivo.
AB  - OBJECTIVE: Amiodarone, a class III antiarrhythmic agent, is a potent coronary
      vasodilator. However, direct evidence for its vasodilatory effects in human
      vasculature in vivo is not available. The aim of the study was to investigate the
      short-term effects of amiodarone in preconstricted human hand veins and to
      explore the underlying mechanisms. METHODS: Thirty-one healthy male volunteers
      were studied with the use of the dorsal hand vein compliance technique. The hand
      veins of the subjects were preconstricted with the alpha 1-adrenergic receptor
      agonist phenylephrine, and amiodarone, inhibitors of nitric oxide formation (NG
      monomethyl-L-arginine, L-NMMA), and adenosine triphosphate-dependent potassium
      channels (glyburide [INN, glibenclamide]) were infused in the presence or absence
      of a cyclooxygenase inhibitor (acetylsalicylic acid), and the venodilator effect
      was measured. Furthermore, amiodarone was infused in prostaglandin F2 alpha
      (dinoprost)-preconstricted hand veins. RESULTS: Amiodarone produced dose
      dependent venodilation (51% +/- 3% maximum). Maximum amiodarone-induced
      venodilation was lower in dinoprost compared with phenylephrine-preconstricted
      veins. Pretreatment with acetylsalicylic acid reduced the amiodarone-induced
      venodilation by 40% +/- 6%. L-NMMA reduced the amiodarone-induced venodilation
      after pretreatment with acetylsalicylic acid by 72% +/- 3%. Glyburide decreased
      the venodilatory response of amiodarone by 31% +/- 11%, whereas only a slight but
      not statistically significant additional reduction in venodilation was detected
      after pretreatment with acetylsalicylic acid. Infusion of the solvents of
      commercially available amiodarone (polysorbate 80 and benzyl alcohol) did not
      cause vasodilation in phenylephrine-preconstricted veins. CONCLUSIONS: Amiodarone
      dilates preconstricted human hand veins in vivo and acts as a venodilator through
      the cyclooxygenase pathway, activation of nitric oxide synthase, and blockade of
      alpha adrenergic mechanisms.

PMID- 9757155
TI  - Dynamic analysis of dofetilide-induced changes in ventricular repolarization.
AB  - OBJECTIVE: To use dynamic electrocardiographic (ECG) techniques to study the
      influence of heart rate on dofetilide-induced QT prolongation among healthy
      volunteers. BACKGROUND: The extent to which heart rate modulates QT prolongation
      induced by the new class III antiarrhythmic drug dofetilide is a matter of
      debate. METHODS: Ten healthy volunteers underwent two 24-hour ECG recordings, one
      in the absence of dofetilide and the other after a single oral dose of 0.5 mg
      dofetilide. Two 4-hour periods were defined during the second recording: Dh,
      which corresponded to stable high concentration of the drug, and D1, which
      corresponded to low concentration of the drug. Corresponding baseline recording
      periods, Ch and C1, matched by time with Dh and D1 were selected from the control
      ECG recording in the absence of dofetilide. QT versus R-R relations were compared
      in the presence and absence of dofetilide. The QT versus R-R relation slope was
      used as an index of the rate dependence QT prolongation. Rate-independent changes
      in QT duration were also analyzed. RESULTS: During Dh, dofetilide induced a mean
      12% lengthening of ventricular repolarization. Dynamic ECG analysis showed that
      this prolongation increased as R-R cycles became longer, a phenomenon known as
      reverse rate dependence. However, QT prolongation persisted at the shortest (600
      ms) R-R cycle length that could be analyzed. During D1, dynamic ECG analysis
      showed a persistent, although small, effect of dofetilide on both QT prolongation
      (3%) and reverse rate dependence of this effect. CONCLUSIONS: Dofetilide prolongs
      QT duration, and this class III effect is influenced by heart rate. Although
      dofetilide-induced QT prolongation decreases when the R-R cycle shortens, this
      reverse rate dependence is only partial because marked QT prolongation persists
      at an R-R cycle of 600 ms. The results of our study indicated that dynamic ECG
      techniques can be useful in detection of subtle, drug-induced changes in the
      duration of ventricular repolarization.

PMID- 9757156
TI  - Hemodynamic effects of continuous urodilatin infusion: a dose-finding study.
AB  - OBJECTIVE: To evaluate the effects of urodilatin (INN, ularitide) on systemic and
      renal hemodynamic parameters. METHODS: Twenty healthy male subjects were included
      in this double-blind, randomized placebo-controlled trial and assigned to receive
      either continuous intravenous infusion of different doses of 7.5, 15, or 22.5
      ng/kg body weight/min urodilatin or placebo over 300 minutes. Cardiac
      performance, systolic time intervals, and airway function were measured
      noninvasively. The effects on renal hemodynamic values were assessed with para
      aminohippurate and inulin clearance techniques. RESULTS: Urodilatin was well
      tolerated by all subjects at doses of 7.5 and 15 ng/kg/min. Infusion was stopped
      prematurely for the group that received 22.5 ng/kg/min urodilatin group because
      of systemic hypotensive responses with nausea and dizziness. Infusion of 15
      ng/kg/min urodilatin significantly increased urine flow by a maximum of 165%,
      filtration fraction by 46%, renal resistance by 49%, and systemic vascular
      resistance by 45%. It decreased renal plasma flow by a maximum of 31% from
      baseline value. No change in cardiac inotropic function was detectable, but
      cardiac output decreased in all dose groups. Effects on glomerular filtration
      rate, forced expiratory volume, blood pressure, and pulse were not different from
      those with placebo. CONCLUSION: Continuous infusion of 7.5 ng/kg/min and 15
      ng/kg/min urodilatin exerts a significant increase in systemic and renal vascular
      resistance. Results of our experiments suggested that the therapeutic window for
      continuous urodilatin infusion is small and that doses higher than approximately
      20 ng/kg/min urodilatin carry high risk for adverse drug reactions.

PMID- 9757157
TI  - Concentration-controlled zidovudine therapy.
AB  - BACKGROUND: Heterogeneity in the response to antiretroviral therapy has been
      attributed to pharmacologic, immunologic, and virologic differences between
      patients. Currently available antiretroviral agents used for the treatment of
      human immunodeficiency virus (HIV) infection in adults are administered in
      standard fixed doses. The active moiety of nucleoside anti-HIV drugs is the
      intracellular anabolite. Therefore the heterogeneity in response to nucleoside
      agents may arise as a result of pharmacologic variability at both the systemic
      and cellular level. OBJECTIVES: To determine whether a novel concentration
      controlled zidovudine regimen could improve anti-HIV response compared with the
      standard fixed-dose approach. DESIGN: At the Outpatient Clinic of the General
      Clinical Research Center at the University of Minnesota, 20 persons with HIV
      infection received an oral regimen of zidovudine designed to achieve a target
      concentration in plasma of 0.7 mumol/L and the 500 mg/day standard dose in a
      randomized, crossover 24-week study. RESULTS: The concentration-controlled
      regimen achieved overall higher systemic concentrations with reduced interpatient
      variability: steady-state average zidovudine plasma concentrations were 0.76
      mumol/L (coefficient of variation, 12%) versus 0.62 mumol/L (coefficient of
      variation, 32%) for the standard regimen. There was no difference in safety and
      tolerance between regimens. Intracellular zidovudine triphosphate concentrations
      averaged 160 fmol/10(6) peripheral blood mononuclear cells (PBMCs) with
      concentration-controlled versus 92 fmol/10(6) PBMCs for standard therapy. The
      percentage change from baseline in CD4 cells was a 22% increase for the
      concentration-controlled regimen versus a 7% decrease with standard therapy.
      CONCLUSIONS: These data indicate that pharmacologic variability affects
      antiretroviral response. Furthermore, these findings provide a framework to
      characterize the pharmacologic determinants of effect and quantitate their
      contribution to the heterogeneity in clinical response to optimize therapeutic
      benefit.

PMID- 9757158
TI  - Phase I study of a humanized anti-CD11/CD18 monoclonal antibody in multiple
      sclerosis.
AB  - OBJECTIVE: To evaluate the safety, pharmacokinetics, pharmacodynamics, and
      immunogenicity of a humanized anti-CD11/CD18 monoclonal antibody (Hu23F2G) in
      patients with multiple sclerosis. METHODS: In this phase I uncontrolled dose
      escalation study, patients (n = 24) with primary or secondary progressive
      multiple sclerosis received single intravenous infusions of Hu23F2G (0.01 to 4.0
      mg/kg). Study parameters included safety, pharmacology, immunogenicity, and brain
      magnetic resonance imaging (MRI). RESULTS: Hu23F2G had few adverse effects, but 2
      cases of urinary tract infection and 2 cases of gingivitis did occur. Transient
      leukocytes developed in some subjects receiving > or = 1.0 mg/kg. The
      pharmacokinetic response was nonlinear, with the area under the curve increasing
      out of proportion to the increase in dose. The mean terminal half-life increased
      with dose and was 21.9 (SD, 12.8) hours at the 4.0 mg/kg dose. High saturation (>
      80%) of CD11/CD18 on circulating leukocytes was achieved with doses > or = 0.2
      mg/kg. The duration of high leukocyte saturation was dose-dependent, persisting
      for more than a week at the 4.0 mg/kg dose. A marked decrease in leukocyte
      migration in response to cutaneous inflammation was observed. Antibodies against
      Hu23F2G were not detected. The neurologic examinations were stable except for 1
      subject who had worsening weakness associated with an infection. No significant
      changes were noted on brain MRI scans. CONCLUSIONS: Hu23F2G was tolerated at
      doses that achieved high degrees of leukocyte CD11/CD118 saturation with in vivo
      inhibition of leukocyte migration. Because this phase I study was not designed to
      determine the clinical efficacy of Hu23F2G, further studies are needed.

PMID- 9757159
TI  - Buspirone plasma concentrations.

PMID- 9757160
TI  - Carcinogen-in-a-can.

PMID- 9757161
TI  - Secondhand smoke and cancer: Where's the proof?

PMID- 9757162
TI  - Evidence for effectiveness of home care.

PMID- 9757163
TI  - Confidentiality in medical publishing.

PMID- 9757164
TI  - Facing reality.

PMID- 9757165
TI  - Marathon's success.

PMID- 9757166
TI  - Understanding Quebec's policy on nursing training.

PMID- 9757167
TI  - National incidence study of child abuse and neglect.

PMID- 9757168
TI  - Recent findings from the Ontario Student Drug Use Survey.
AB  - BACKGROUND: Every 2 years, the Addiction Research Foundation of Ontario, a
      division of the Centre for Addiction and Mental Health, sponsors the Ontario
      Student Drug Use Survey. The results of the surveys conducted in 1995 and 1997
      are presented here and compared with results from the early 1990s. METHODS:
      Questionnaires were completed by 3870 and 3990 Ontario public school students
      enrolled in grades 7, 9, 11 and 13 in 1995 and 1997 respectively. The outcome
      measures were prevalence of use of 20 types of drugs and other substances,
      including alcohol, tobacco and prescription drugs, over the previous 12 months.
      RESULTS: For several drugs the prevalence of use in the previous 12 months had
      increased from 1993 to 1995, but from 1995 to 1997 there was a significant
      increase for only one type (hallucinogens such as mescaline and psilocybin). The
      inhalation of glue declined, and the use of the other 18 types of drugs remained
      stable. INTERPRETATION: Recent data suggest that increases in adolescent student
      drug use reported earlier this decade have not continued. However, the stability
      in rates of drug use is not a justification for complacency in this important
      area of public health.

PMID- 9757169
TI  - Relation between severity of Alzheimer's disease and costs of caring.
AB  - BACKGROUND: Data from the Canadian Study of Health and Aging (CSHA) were used to
      examine the relation between severity of Alzheimer's disease, as measured by the
      Mini-Mental State Examination (MMSE), and costs of caring. METHODS: The CSHA was
      a community-based survey of the prevalence of dementia, including subtypes such
      as Alzheimer's disease, among elderly Canadians. Survey subjects with a diagnosis
      of possible or probable Alzheimer's disease were grouped into disease severity
      levels of mild (MMSE score 21-26), mild to moderate (MMSE score 15-20), moderate
      (MMSE score 10-14) and severe (MMSE score below 10). Components of care available
      from the CSHA were use of nursing home care, use of medications, use of community
      support services by caregivers and unpaid caregiver time. Costs were calculated
      from a societal perspective and are expressed in 1996 Canadian dollars. RESULTS:
      The annual societal cost of care per patient increased significantly with
      severity of Alzheimer's disease. The cost per patient was estimated to be $9451
      for mild disease, $16,054 for mild to moderate disease, $25,724 for moderate
      disease and $36,794 for severe disease. Institutionalization was the largest
      component of cost, accounting for as much as 84% of the cost for people with
      severe disease. For subjects living in the community, unpaid caregiver time and
      use of community services were the greatest components of cost and increased with
      disease severity. INTERPRETATION: The societal cost of care of Alzheimer's
      disease increases drastically with increasing disease severity.
      Institutionalization is responsible for the largest cost component.

PMID- 9757171
TI  - Secrecy and the health protection branch.

PMID- 9757170
TI  - The antihypertensive efficacy of losartan and amlodipine assessed with office and
      ambulatory blood pressure monitoring. Canadian Cozaar Hyzaar Amlodipine Trial
      Study Group.
AB  - BACKGROUND: Losartan potassium is a recently marketed angiotensin II receptor
      antagonist. Previous studies have suggested that its full antihypertensive
      efficacy may be delayed for up to 12 weeks. The authors compared the
      antihypertensive efficacy and tolerability of losartan at 6 and 12 weeks with
      those of amlodipine besylate, a commonly used calcium antagonist. METHODS: This
      multicentre, randomized, double-blind clinical trial studied 302 patients with
      mild or moderate hypertension in 1995. Of the 302, 97 also underwent ambulatory
      blood pressure monitoring (ABPM). After a 4-week placebo run-in period, the
      patients were randomly assigned to group A, B or C for 12 weeks. Those in groups
      A and B began treatment with losartan at 50mg/d, and those in group C began with
      amlodipine at 5 mg/d. If the blood pressure remained uncontrolled after 6 weeks,
      subjects in group A had their losartan dose doubled (to 100 mg/d), those in group
      B were given hydrochlorothiazide (12.5 mg/d) in addition to the losartan, which
      remained at 50 mg/d, and patients in group C had their amlodipine dose doubled
      (to 10 mg/d). RESULTS: At 12 weeks all 3 regimens reduced office-recorded
      diastolic blood pressure (DBP) with the patient sitting. The mean reduction in
      group A was 8.7 mm Hg (95% confidence interval [CI] 7.3 to 10.1) (p < 0.001), in
      group B 12.5 mm Hg (95% CI 11.0 to 14.0) (p < 0.001) and in group C 12.9 mm Hg
      (95% CI 11.4 to 14.5) (p < 0.001). Losartan alone lowered sitting DBP to a lesser
      degree than the other 2 treatments (p < 0.01). In contrast, ABPM readings,
      whether 24-hour, daytime or nighttime, were not different among the regimens.
      Comparison of the results at 6 weeks yielded similar findings. Adverse effects
      were uncommon and were not different among the groups, with the exception of
      ankle edema, which was more frequent in group C. INTERPRETATION: Losartan alone
      reduces both office and ABPM readings. The observed changes in office-recorded
      sitting DBP suggest that losartan is less effective than amlodipine or the
      combination of losartan and hydrochlorothiazide, but ABPM did not confirm this
      difference. Perhaps changes in office readings measure different attributes of a
      drug than does ABPM.

PMID- 9757172
TI  - A time for everything: changing attitudes and approaches to reducing substance
      abuse.

PMID- 9757173
TI  - Randomized clinical trials of antihypertensive drugs: all that glitters is not
      gold.

PMID- 9757174
TI  - Prostate cancer: progress and perplexity.

PMID- 9757175
TI  - Funding Canada's health care system: a tax-based alternative to privatization.

PMID- 9757176
TI  - Still here, still flawed, still wrong: the case against the case for taxing the
      sick.

PMID- 9757177
TI  - Patient consent for publication--an apology.

PMID- 9757178
TI  - Prostate cancer: 1. The descriptive epidemiology in Canada.
AB  - A 70-year-old woman who experienced a long period of depression after her first
      husband's death from prostate cancer at the age of 63 has become increasingly
      anxious about her own health and that of her close family. A few years ago she
      married a man her own age; he is in good physical condition. Last year the family
      spent much of the winter in Florida, where the woman noticed several studies in
      the media suggesting that an epidemic of prostate cancer is occurring in North
      America and that because early detection can save lives men of retirement age
      should be checked by their physicians as soon as possible. In addition, 2 close
      friends recently diagnosed with prostate cancer. On his latest fishing trip her
      husband learned from a friend that 1 in 8 men get prostate cancer. He has not
      seen his family physician for several years, but his wife has booked an
      appointment for them to discuss their concerns.

PMID- 9757179
TI  - Ascending the magic mountain.

PMID- 9757180
TI  - Chronic fatigue syndrome or just plain tired?

PMID- 9757181
TI  - Anemic loonie begins to affect health care sector.
AB  - Although most news surrounding the declining dollar has concentrated on its
      impact on Canadian shoppers, economists say it is bound to affect the financially
      strapped health care system too. They point out that many of the good purchased
      by Canadian hospitals come from the US, and the weak loonie means their price
      will rise.

PMID- 9757182
TI  - Results from CMA's huge 1998 physician survey point to a dispirited profession.
AB  - Results from the CMA's 1998 Physician Resource Questionnaire are in, and they
      point to a serious decline in physician morale. The PRQ, the country's most
      important poll of physician attitudes, provides an annual "state-of-the-nation"
      message for the medical profession.

PMID- 9757183
TI  - Chronic fatigue syndrome get court's nod of approval as legitimate disorder.
AB  - Lawyer Karen Capen looks at the implications of a recent Alberta court case
      involving chronic fatigue syndrome. She thinks Canada's physicians should pay
      close attention to this precedent-setting case.

PMID- 9757184
TI  - Chronic fatigue syndrome comes out of the closet.
AB  - An Alberta court ruling and new guidelines for physicians issued by the Quebec
      medical college are giving chronic fatigue syndrome a legitimacy it never before
      enjoyed. What will this mean for physicians?

PMID- 9757185
TI  - Offshore energy boom providing opportunities outside Medicare's umbrella.
AB  - Physicians upset by limits imposed by the medicare system are getting a chance to
      spread their entrepreneurial wings on the East Coast. A boom in offshore
      exploration, led by Newfoundland's massive Hibernia project, has led to numerous
      business opportunities for physicians.

PMID- 9757186
TI  - New private facility woos public dollars in Calgary.
AB  - The opening of a private wing in an old hospital has caused consternation in
      Calgary because some people consider it a beachhead for private medicine.

PMID- 9757187
TI  - [Meta-analysis of clinical trials for chemotherapy in cancer].
AB  - Meta-analysis has attracted great interest among clinical practitioners in recent
      years, leading to a steady output of related publications. Meta-analytic articles
      are easily found in the MEDLINE database using the publication-type option. This
      paper reviews how to use and understand meta-analysis with a special reference to
      chemotherapy applied to cancer patients. It is described in relationship to
      evidence-based medicine (EBM) and clinical practice guidelines. Cochrane
      collaboration is also referred to as an active voluntary organization conducting
      meta-analysis. In the technical sections, statistical issues and graphic
      representations are clearly illustrated using the example of hepatic arterial
      infusion for colorectal cancer patients. The difference between fixed and random
      effects models is briefly explained. Finally, an example from Cochrane Library,
      namely progestagen therapy for endometrial cancer, is illustrated to show the
      implications of meta-analysis for clinical practice.

PMID- 9757188
TI  - [Controversy on treatments for gliomas].
AB  - Gliomas are representative primary malignant brain tumors, and with such tumors
      it is difficult to define the advanced stage. If the advanced stage indicates no
      curability by surgery alone, most gliomas would belong to this criterion because
      of their poor prognosis without any completely effective treatment. In this
      sense, no one could show a standard therapy to treat these unfortunate patients,
      for example, patients with glioblastoma, they could permit only 1 year survived
      even they had any applicable treatments to the lesions, these days. Treatment for
      low-grade gliomas has been most controversial for a long time, and no standard
      treatments have been determined so far. In this paper, as the treatment of low
      grade gliomas it was intended to report what must be done for this patient and
      the present results of opinion survey for the treatment of gliomas which was done
      to professors of 80 institutes, from schools of medicine at all universities and
      medical colleges in Japan. For high-grade gliomas, some effectiveness of
      radiation therapy was disclosed as well as chemotherapy from recent papers. Gene
      therapy was also discussed briefly, its present status and future.

PMID- 9757189
TI  - [Recent treatment modality for advanced head and neck carcinomas].
AB  - Histopathologically, about 90% of head and neck cancer is squamous cell
      carcinoma. The curative treatments for head and neck cancer are conventional
      radiotherapy and/or surgical resection. Multidisciplinary treatment, including
      combinations of the curative therapy, chemotherapy and immunotherapy, has been
      applied for advanced head and neck carcinomas with poor outcomes. Nowadays,
      chemotherapy is under investigation in the neo-adjuvant, adjuvant and concurrent
      chemoradiotherapy. In this paper, the treatment approach was reviewed in terms of
      prognostic factors which have been retrospectively estimated, along with recent
      developments in treatment modalities of advanced cases.

PMID- 9757190
TI  - [Recent issue in the treatment of small-cell lung cancer].
AB  - Chemotherapy is currently a primary treatment modality for small-cell lung cancer
      (SCLC). However, in the limited stage, a combination of chemotherapy and thoracic
      irradiation (TI) was found to be superior to chemotherapy alone by meta-analysis.
      Recently, concurrent administration of cisplatin and etoposide with TI may be an
      optimal treatment. The usefulness of prophylactic cranial irradiation in complete
      responders was also confirmed by meta-analysis. Dose-intensive weekly
      chemotherapy failed to improve the treatment outcome in the extensive stage.
      Randomized trials to verify the effectiveness of high-dose chemotherapy with
      peripheral blood stem cell transplantation are in progress.

PMID- 9757191
TI  - [Recent issues in the treatment of advanced non-small-cell lung cancer].
AB  - Unfortunately, most patients with non-small cell lung cancer (NSCLC) present with
      clinically unresectable advanced neoplasms. Since local treatment like surgery
      and radiation is not satisfactory for advanced NSCLC, effective systemic
      chemotherapy is necessary. But NSCLC is relatively resistant to chemotherapy.
      This report discusses the some recent issues in the treatment for advanced NSCLC.
      the issues are the following: 1) effect of post-operative chemotherapy and pre
      operative induction chemotherapy in the patients with stage IIIA N2 disease; 2)
      efficacy combining chemotherapy with thoracic radiotherapy (TRT) in unresectable,
      locally advanced NSCLC; 3) timely combination of TRT and chemotherapy; 4) effect
      of chemotherapeutic agents as radiosensitizer; 5) potential effect of combination
      of TRT and new agents in unresectable, locally advanced NSCLC; 6) contribution of
      surgery following induction chemo-radiotherapy in locally advanced NSCLC; 7)
      reasons why response rate in cancer chemotherapy for advanced NSCLC does not
      always correlate with survival; 8) survival benefit of cancer chemotherapy in
      metastatic NSCLC; and 9) promising new agents (irinotecan, paclitaxel, docetaxel,
      vinorelbine and gemcitabine) along with combination chemotherapy, including these
      new agents.

PMID- 9757192
TI  - [Update of ovarian carcinoma].
AB  - Correct histopathologic diagnosis of ovarian carcinoma is essential, because
      biological behavior of the disease varies by the histologic subtype and its grade
      of differentiation. The standard treatment modality of advanced ovarian carcinoma
      has consisted of an initial maximal surgical effort and subsequent platinum-based
      chemotherapy, followed by a secondary surgery. "Maximal surgical effort" is a
      convenient term but it does not define a surgical procedure. In USA, since 1996,
      paclitaxel/cisplatin had become a 1st-line regimen. Introduction of other potent
      agents including topotecan/CPT-11 and previous evidence of the efficacy of
      doxorubicin have made it difficult to decide which regimen is the most potent. A
      maximal effort should be made at the second surgical attempt after completing a
      planned 1st regimen. Finally, we should obtain a pathologically complete response
      with the combined use of surgery and chemotherapy to achieve long-term survival
      in patients with advanced ovarian carcinoma.

PMID- 9757193
TI  - [Treatment of advanced cervical cancer].
AB  - Patients with advanced-stage cervical cancer are treated with radiation. Although
      5-year survival rates of about 40 percent are reported, there is clearly room for
      improvement. The potential usefulness of neoadjuvant chemotherapy (NAC) before
      planned surgery is under investigation. The clinical response to NAC seems to be
      related to survival. Neoadjuvant chemotherapy before planned radiation therapy
      has not been demonstrated to provide a benefit. In the area of concomitant
      chemotherapy and radiation, a number of clinical trials have been completed or
      are under way, but at this time there is no proven benefit to combining
      chemotherapy with radiation. It is very interesting that concomitant weekly
      cisplatin and prophylactic paraaortic radiation was reported to improve survival.

PMID- 9757194
TI  - [Recent controversy in treatment for advanced bladder cancer].
AB  - We summarized here the current status and controversy surrounding treatment for
      advanced bladder cancer, which may be defined as deeply invasive bladder cancer
      or invasive bladder cancer with distant metastasis. The definitive treatment for
      advanced bladder cancer is considered to be systemic chemotherapy. However,
      favorable results are not always obtained from CDDP-based combination
      chemotherapy alone. Therefore, the development of a dose-intensified regimen
      using G-CSF, intra-arterial chemotherapy, based on the concept of the drug
      delivery system, and combination therapy of radiation and chemotherapy, produced
      better results. Surgical treatment, a part of a multidisciplinary approach, may
      result in a complete response followed by a good prognosis.

PMID- 9757195
TI  - [Chemotherapy for pulmonary metastases of soft tissue sarcoma].
AB  - The role and value of chemotherapy for soft tissue sarcomas remain unclear.
      Seventeen patients with pulmonary metastatic soft tissue sarcomas underwent
      treatment with chemotherapy, and the clinical efficacy and prognosis were
      studied. Six patients with synovial sarcomas, 4 with malignant fibrous
      histiocytomas, 4 with neurosarcomas, and the remaining 3 patients with
      leiomyosarcoma, extraskeletal osteosarcoma, and extraskeletal chondrosarcoma,
      were studied. Cases with small round cell sarcomas were excluded. The
      chemotherapy agents were ifosfamide in 10 cases, combination of ifosfamide and
      adriamycin in 5 cases, or cisplatin and adriamycin in 2 cases. Of the 17
      patients, seven had partial responses radiographically and five had pulmonary
      metastases from synovial sarcoma. Eight patients underwent resection of pulmonary
      metastases following chemotherapy, and they were found to be residual tumor cells
      histologically. Twelve of the patients died of disease at 6-108 months (median,
      30 months) from the time of the initial therapy, and five patients have survived
      from 1-53 months (median, 30 months). The absolute three-year survival rate,
      according to the Kaplan-Meier method, for all 17 patients was 39%. In the two
      cases with no change and progressive disease, all patients were dead within 2
      years, while in the seven partial response cases, two patients were dead, four
      were alive with pulmonary metastases, and only one case was disease-free at this
      writing. The survival rate for patients with partial response was significantly
      higher than for patients with no response. Although the cure rate of pulmonary
      metastatic soft tissue sarcomas is still low, the combination of chemotherapy and
      surgery has been shown to result in prolonged survival.

PMID- 9757196
TI  - [Effect on hepatic function of hepatic artery infusion chemotherapy using
      epirubicin and mitoxantrone for advanced hepatocellular carcinoma].
AB  - This study was designed to assess the effect of hepatic dysfunction from hepatic
      artery infusion (HAI) in advanced hepatocellular carcinoma (HCC). The patients
      were randomly assigned to receive epirubicin (n = 12, Epi group) or mitoxantrone
      (n = 14, Mito group) once every 4 weeks between 1992 and 1996. HCC patients were
      given 6-8 mg of mitoxantrone or 30-40 mg epirubicin. There was hepatic
      dysfunction in 27 patients after HAI, showing similarly elevated GOT, GPT, and
      total bilirubin. In the Epi group, the GOT value was slightly higher than in the
      Mito group, but it was not significant. After HAI chemotherapy, the GOT value
      showed a more than two-fold elevation. Six patients in the Epi group and 2 in the
      Mito group showed a significant difference. Our results indicated that
      mitoxantrone had less impact on hepatic function following HAI therapy.

PMID- 9757197
TI  - [Results of clinical study with epirubicin hydrochloride injectable solution in
      hepatoma].
AB  - A 10-center cooperative clinical study with a new formulation of epirubicin
      hydrochloride injectable solution (Epirubicin-RTU) was conducted in patients with
      hepatocellular carcinoma. Epirubicin-RTU 60 mg/m2 was injected into the hepatic
      artery and a three-week drug-free interval followed. Of 15 patients with
      hepatocellular carcinoma registered in this study, 14 patients were eligible, and
      they all completed the entire course. The objective was to investigate the safety
      of treatment with Epirubicin-RTU in 14 eligible patients. The adverse drug
      reactions frequently observed in these 14 eligible cases were leukopenia,
      neutropenia, thrombocytopenia, alopecia, and fever. They were all reversible and
      tolerable. With these results. Epirubicin-RTU was considered to be a safe
      pharmaceutical product to inject into the hepatic artery.

PMID- 9757198
TI  - [Results of clinical study with epirubicin hydrochloride injectable solution and
      cyclophosphamide in breast cancer].
AB  - A 10-center cooperative clinical study with a new formulation of epirubicin
      hydrochloride injectable solution (Epirubicin-RTU) was conducted in patients with
      breast cancer. One course of treatment consisted of one intravenous
      administration of Epirubicin-RTU at the dose of 60 mg/m2 followed by a 3-week
      drug-free interval and concomitant daily administration of oral cyclophosphamide
      at 100 mg/day during the period between Days 1 through 14. At least, two courses
      of treatment were given. Among 20 registered cases, all 20 cases were eligible
      and 16 cases completed the whole course of the study. In 16 completers, PR was
      observed in 5 cases, indicating the efficacy rate of 31.3% (5/16).. No local
      irritation was observed at the injection sites. Adverse reactions frequently
      observed were leukopenia, neutropenia, anorexia, alopecia, and nausea/vomiting,
      which were all reversible and tolerable. From the above results, Adverse
      reactions both locally and systemically were tolerable. Intravenous
      administration of Epirubicin-RTU was considered to be useful for the treatment of
      breast cancer.

PMID- 9757199
TI  - [Mobilization of peripheral blood stem cells in advanced ovarian cancer].
AB  - High-dose chemotherapy with hematopoietic support has been expected to improve
      the survival of advanced ovarian cancer patients in recent years. An essential
      component of such treatment has been the ability to collect and reinfuse a large
      number of peripheral blood stem cells (PBSCs) following high dose therapy. This
      study was designed to determine which clinical and hematological factors would be
      better indicators to collect the proper volume of PBSCs. Thirteen patients
      received a total of 24 courses of induction chemotherapy and 69 of apheresis. We
      usually mobilized stem cells using CEP chemotherapy (cisplatin 50-70 mg/m2,
      epirubicin 50 mg/m2 and cyclophosphamide 1.5 g/m2) with G-CSF and CEE regimen
      (cyclophosphamide 2.0 g/m2, epirubicin 50 mg/m2, and etoposide 50 mg/m2) as a
      salvage for mobilization. We obtained an average 5 x 10(6)/kg of CD34+ cells for
      3 days as one course. The number of CD34+ cells collected significantly depended
      on the platelets and reticulocytes on the first day of apheresis, but not a nadir
      of WBCs. It is concluded that apheresis should be started on recovery of WBCs to
      5,000-10,000/microliters, of immature granulocytes to > or = 10% and of
      reticulocytes to > or = 20%. This study confirmed the feasibility of collecting
      enough PBSCs to use standard chemotherapy of ovarian cancer patients.

PMID- 9757200
TI  - [High-dose chemotherapy with autologous peripheral blood stem cell transfusion in
      the treatment of advanced testis cancer].
AB  - Four patients with advanced testis cancer were treated by high-dose chemotherapy
      supporting by autologous peripheral blood stem cell transplantation. High-dose
      chemotherapy (carboplatin 250 mg/m2 or nedaplatin 200 mg/m2, etoposide 1,500
      mg/m2, ifosphamide 7.5 g/m2 was given and peripheral blood stem cell transfusion
      was performed 72 hours after the last dose of chemotherapy. High-dose
      chemotherapy. was given followed by 1 or 2 cycles of pre high-dose therapy
      consisting of cisplatin 100 mg/m2 or carboplatin 500 mg/m2, etoposide 450 mg/m2,
      ifosphamide 6 g/m2. All 4 patients were evaluable. Three patients obtained a
      complete response and one showed a partial response. The partial responder was
      given RPLND. The RPLND specimen showed necrotic tissue.

PMID- 9757201
TI  - [Efficacy and safety of two methods of administration of granisetron injection
      for nausea and vomiting induced by chemotherapy for tumors in hematopoietic
      organs--a randomized crossover comparison between intravenous drip infusion and
      intravenous bolus injection].
AB  - We investigated the efficacy and safety of two methods of granisetron injection
      to treat nausea and vomiting induced by chemotherapy for tumors in hematopoietic
      organs. The methods of administration were intravenous drip infusion over 30
      minutes, which is the conventional method, and intravenous bolus injection. In
      this study, 89.5% of patients in both groups (17/19 for each) were free from
      vomiting. No serious adverse events were observed in either administration group.
      Abnormal laboratory test values suspected to be related to granisetron were
      observed in 3 cases in the bolus injection group and in 2 cases in the drip
      infusion group. but did not pose any clinical problem. These results demonstrated
      the safety of both methods of administration. In conclusion, it is considered
      that granisetron intravenous bolus injection can be considered as the method of
      choice for the prevention of nausea and vomiting induced by chemotherapy for
      tumors in hematopoietic organs.

PMID- 9757202
TI  - [Effect of combination chemotherapy of low-dose CDDP. Continuous infusion of 5
      FU, and intermittent CPT-11 administration for 2 advanced pancreatic cancer cases
      with liver metastasis].
AB  - For advanced pancreatic cancer, there is no typical chemotherapy regimen non
      single chemotherapeutic agent. For example, 5-FU, Doxorubicin, MMC and Epirubicin
      obtained only 15-24% efficacy, and general combination chemotherapy was FAM, 5
      FU+CDDP and 5-FU+Leucovorin for pancreatic cancer. Generally, in pancreatic
      cancer cases the performance status was poor, and most could not endure the
      chemotherapy regimen. 5-FU continuous infusion and low-dose CDDP regimen were
      effective and showed fewer side effects for pancreatic cancer. Then, for 2 cases
      of advanced pancreatic cancer with liver metastasis, 5-FU continuous infusion +
      low-dose CDDP + intermittent CPT-11 administration (5-FU 500 mg/body/24 hr + CDDP
      5mg x 5 days-6 courses + CPT-11 100 mg-125 mg-150 mg, bolus i.v. intermittently)
      was effective. Thus, this regimen could well be effective for advanced pancreatic
      carcinoma.

PMID- 9757203
TI  - [Three cases of colorectal cancer with lung metastasis successfully treated with
      combination chemotherapy using 5'-DFUR and MMC].
AB  - Three patients with colorectal cancer and pulmonary metastasis who had previously
      undergone surgical treatment, were treated by combination chemotherapy with CDDP
      and 5-FU regimen, but the growth of the metastatic tumor could not be controlled
      finally. Thus, a new strategy of combination chemotherapy using 5'-DFUR and MMC
      were investigated in these cases, and resulted in suppressing the tumor growth
      successfully without admission. The procedure for treating pulmonary metastasis
      of colorectal cancer has not been established clearly. This new regimen may play
      an important role from the standpoint of not only its effectiveness against tumor
      growth but also the quality of life of patients.

PMID- 9757204
TI  - [Complete remission of liver metastasis from rectal cancer following continuous
      oral administration of tegafur-uracil after intrahepatic arterial single
      injection of CDDP and 5-FU].
AB  - An intrahepatic arterial injection of CDDP, 5-FU, followed by ten months of oral
      tegafur-uracil administration (2g/day), induced remission for 3 months or more in
      a 72-year-old male with rectal cancer and synchronous liver metastasis subsequent
      to anterior resection of the rectum. Tegafur-uracil showed an excellent
      anticancer effect against colorectal metastatic liver cancers without loss of QOL
      because a single-low dose of intraarterial anticancer injection was followed by
      continuous oral administration of tegafur-uracil, and the chemotherapy could be
      managed to obtain complete remission of the hepatic lesion.

PMID- 9757205
TI  - [Appropriate intravesical retention time of pirarubicin concentration based on
      its level in tumor tissue, anti-tumor effect and side effect in intravesical
      instillation therapy for bladder tumor].
AB  - The present study was designed to investigate the appropriate intravesical
      retention time of pirarubicin (THP) for the treatment of bladder tumor in terms
      of its anti-tumor effect and side effect. We administered THP to 22 patients with
      superficial bladder tumor intravesically and measured the THP concentration in
      the tumor tissues. Patients were divided into 3 groups by retention time; 8 for
      30 minutes, 8 for 1 hour and 7 for 2 hours. Tumor tissues were obtained by
      transurethral resection 30 min., 1 or 2 hours after the intravesical instillation
      of THP at the fixed concentrations of 30 mg/30 ml. There was no significant
      difference in THP concentration between 3 groups. This indicates that the anti
      tumor effect of intravesical instillation of the THP would be expected by only 30
      min. of intravesical retention time at the THP concentration of 30 mg/30 ml.
      Then, we administered 30 mg/30 ml of THP solution for 30 min. to 10 patients
      intravesically 6 times every 48 hours to investigate its clinical anti-tumor
      effect and side effect. There were 2 complete responses, 3 partial responses and
      5 cases with no changes for a total response rate of 50%. No side effect was
      observed. It is considered that 30 min. of intravesical retention time at the THP
      concentration of 30 mg/30 ml would be appropriate in terms of its anti-tumor
      effect and side effect.

PMID- 9757206
TI  - [Increased effect of neocarzinostatin bound to chimeric Fab fragments of
      monoclonal antibody A7 on the proliferation of human pancreatic carcinoma].

PMID- 9757208
TI  - [Comparative study of 5'-DFUR administration of single time per day versus two or
      three times].

PMID- 9757207
TI  - [The correlation between thymidine phosphorylase activity of renal cancer cells
      and the chemosensitivity to 5-FU and 5'-DFUR].

PMID- 9757209
TI  - [Comparative study of 5'-DFUR administration in patients with elderly cancer].

PMID- 9757210
TI  - [TNM classification: cancer of the stomach].
AB  - The 5th edition of TNM Classification was published by the UICC (International
      Union Against Cancer) in 1997. In the classification of gastric cancer,
      anatomical subsites and N category were newly published. The new classification
      and role of the Japanese TNM Joint Committee were described in this paper. The
      Japanese committee had strongly advocated to continue "the anatomical N
      classification", because the hazard ratios were more significant for prognosis of
      patients with gastric cancer, and had many reasonable and scientific advantages.
      However, the UICC introduced "a new N classification by number of metastatic
      lymph nodes" because of the difficulty in studying nodes by anatomical
      classification. The new TNM can not be considered an improved classification, and
      so we are looking for a more scientific, practical, and internationally
      acceptable classification.

PMID- 9757213
TI  - [MRI and traumatic osteoarticular pathology: for a rational application].

PMID- 9757214
TI  - [Percutaneous transhepatic biliary drainage].

PMID- 9757215
TI  - [Diagnostic imaging of acute pulmonary embolism: critical analysis of the 1997
      literature].
AB  - With variable symptoms and a nonspecific radiographic appearance, acute pulmonary
      embolism (APE) is a frequent and often undiagnosed cause of mortality and
      morbidity; thus, availability of an accurate, noninvasive screening examination
      is highly desirable. Until recently, various noninvasive imaging procedures have
      been used to detect APE, including ventilation-perfusion scanning, MR imaging and
      phlebography (or sonography). The low specificity of scintigraphy explains why
      pulmonary angiography remains the usual "gold standard" modality for detection of
      APE. However, with this procedure morbidity and mortality not zero-Helical
      computed tomography (HCT) seems to be an accurate technique for diagnosis of
      pulmonary embolism except for distal thrombi. Nevertheless the exact position of
      HCT in the classic algorithms remains to be defined, particularly in terms or
      cost-benefit results.

PMID- 9757216
TI  - [Imaging cranial nerves with inframillimetric T2-weighted MRI].
AB  - Fifty files were evaluated to determine the normal anatomy of the cranial nerves.
      All the cranial nerves were studied including the labyrinth, in different planes
      with a 3DFT-CISS imaging technique. The 3DFT-CISS is especially interesting to
      study cranial nerves because of the excellent contrast with CSF-fluid and the
      possibility of thin sections. It might be essential for the diagnosis of
      neuralgia and cranial nerves paralysis.

PMID- 9757217
TI  - [Comparative study of tumor evaluation with computerized tomography and surgery
      in ovarian cancer].
AB  - PURPOSE: To evaluate the results of an abdomino-pelvic scan in cancers of the
      ovary in comparison with surgery. MATERIAL AND METHODS: We reviewed the
      observations concerning patients operated on for malignant tumors of the ovary
      between January 1992 and April 1995 in our anti-cancer center. We selected 32
      patients who had had both a complete surgical abdominal exploration (laparotomy
      or laparoscopy) and an abdominal pelvic scan in the preceding months. We divided
      the abdomen into 33 areas and compared the scan of each with the surgical
      findings. Two cancer radiologists, including one gynecology specialist, studied
      the imaging separately. Neither knew the results of the surgical observations.
      RESULTS: Imaging findings varied with localization tumor size and presence or not
      of ascites radiologists. For certain localization, detection of lesions was
      difficult for both readers (pancreas, spleen, stomach), for others, recognition
      improved with experience (bowel, diaphragm, colon). CONCLUSION: The clinician
      must be aware of the variability of ovarian cancer assessment by CT scan,
      particularly if imaging alone is being used to guide treatment.

PMID- 9757218
TI  - [Esophageal morphology with ultrasound imaging after laryngectomy: effect on
      quality of esophageal speech].
AB  - PURPOSE: In patients with aerodigestive cancer, laryngectomy places the esophagus
      in a superficial position, allowing easy ultrasound examination of this organ.
      The purpose of the present study was to assess oesophagus morphology after
      laryngectomy using echotomography and to compare this morphology with voice
      quality. MATERIAL AND METHODS: In the present study, ultrasonography was
      performed in 28 patients (delay from surgery: 3 +/- 3 years): 15 were operated
      using laryngectomy technique (LT) and 13 with pharyngolaryngectomy technique
      (PLT). On transversal echography, antero-posterior and latero-lateral diameters,
      esophagus area and dilatation during phonation were systematically measured.
      These data were compared to the voice quality assessed by two independent
      observers. RESULTS: A smaller latero-lateral diameter and area were found in the
      PLT group than in the LT group (p < 0.05) with a flat aspect in group LT. This
      was associated with faster and better voice acquisition in the PLT group.
      CONCLUSION: Morphologic study of the esophagus after laryngectomy using
      ultrasound is in favor of pharyngolaryngectomy technique which allows better
      conditions for acquiring esophageal voice in better conditions. This could be due
      to the small area, circle shape and tonicity of the esophagus after this type of
      surgery.

PMID- 9757219
TI  - [Percutaneous self-expanding metallic endoprosthesis and malignant biliary
      stenoses].
AB  - METHOD: Thirty-five patients with malignant obstructive jaundice were given
      palliative treatment by percutaneous self-expandable metallic stents.
      Cholangiocarcinoma was the most frequent cause of biliary obstruction. The
      stricture was located in the hilum in more of 50% of cases. RESULTS: Adequate
      biliary drainage was achieved in 97% of cases. Median survival was 182 days. 11%
      of patients have died within 30 days. Early complications occurred in 31% of
      patients. 25% of patients have shown recurrent jaundice after an average of 180
      days. CONCLUSION: Percutaneous self-expandable metallic stents are an efficient
      means treating malignant biliary strictures, particularly of upper biliary
      obstructions.

PMID- 9757220
TI  - [Magnetic resonance imaging of tibial periostitis].
AB  - Tibial periostitis frequently occurs in athletes. We present our experience with
      MRI in a series of 7 patients (11 legs) with this condition. The clinical
      presentation and scintigraphic scanning suggested the diagnosis. MRI exploration
      of 11 legs demonstrated a high band-like juxta-osseous signal enhancement of SE
      and IR T2 weighted sequences in 6 cases, a signal enhancement after i.v. contrast
      administration in 4. Tibial periostitis is a clinical diagnosis and MRI and
      scintigraphic findings can be used to assure the differential diagnosis in
      difficult cases with stress fracture. MRI can visualize juxta-osseous edematous
      and inflammatory reactions and an increased signal would appear to be
      characteristic when the band-like image is fixed to the periosteum.

PMID- 9757221
TI  - [Ureteral hematoma complicating anticoagulant treatment].
AB  - Submucosal hemorrhage of the ureters, are a very uncommon quoted cause of
      hematuria when overdosing anticoagulants. We report two cases, CT shows some very
      typical aspects but can also highlight, as reported formerly, another associated
      complication: parietal hematoma of the small bowel.

PMID- 9757222
TI  - [Rare cause of ischemic cerebrovascular infarct in a young patient: cardiac
      hydatic cyst].
AB  - The authors report the case of a 28-year-old man in whom the diagnosis of hydatic
      cyst of the heart was strongly suspected on echocardiography and CT-scan and
      confirmed by surgery. The interest of this case is based the total clinical
      latency of this hydatic cyst discovered by echocardiography during a systematic
      checkup for cerebrovascular disorders. Echocardiography and spiral scanography
      with bidimensionnal reconstruction in coronal and sagittal planes allowed a rapid
      anatomic and topographic diagnosis. CT-scan also identified spread of
      echinococcosis and discovered a calcifield hydatid cyst of the liver and a
      multivesicular hydatid cyst of the left kidney.

PMID- 9757223
TI  - [Intrathoracic dislocation fracture of the head of the humerus].
AB  - We present a rare case of fracture-dislocation of shoulder with intrathoracic
      displacement of the humeral head. This case is well documented by CT. The
      mechanism and treatment modalities are discussed, and pertinent literature is
      reviewed.

PMID- 9757224
TI  - [Left aortic arch with right descending aorta and right ligamentum arteriosum in
      an infant].
AB  - A rare form of vascular ring, consisting of a left aortic arch, a right
      descending aorta and a right ligamentum arteriosum is reported in a symptomatic
      infant. The role of MRI in the surgical planning is emphasized.

PMID- 9757225
TI  - [What diagnosis? Appendicular abscess].

PMID- 9757226
TI  - [MRI cholangiopancreatography and future exploration of ductal structures:
      tournedos or carpaccio?].

PMID- 9757227
TI  - [Organizations and networks. The English, the Americans...and us?].

PMID- 9757228
TI  - [What is bright on T1 MRI scans?].
AB  - The list of entities associated with a high signal intensity on T1-weighted
      images is extensive and classically includes fat, proteins, hemorrhage, melanin
      and gadolinium. However, additional entities may be responsible for abnormally
      high signal intensity on T1-weighted images. These include ion deposition in
      metabolic disorders, free radicals, increased proton density, flow phenomena,
      some artifacts, and new contrast agents. The aim of this article is to display
      both the common and uncommon causes for a high T1 signal intensity and to discuss
      the underlying mechanisms or attributable pathophysiology for this phenomenon.

PMID- 9757229
TI  - [Puerperal thrombophlebitis and the ovarian vein with extension to the inferior
      vena cava].
AB  - PURPOSE: To assess US, CT and MR findings in women having puerperal ovarian vein
      thrombosis with clot protrusion into the inferior vena cava. PATIENTS, MATERIAL
      AND METHODS: We retrospectively reviewed the duplex US (n = 9), CT (n = 5) and MR
      (n = 5) examinations of 9 patients with 8 right ovarian vein thrombosis, and one
      left ovarian vein thrombosis. RESULTS: US findings allowed for the diagnosis of
      ovarian vein thrombosis in all patients in showing enlarged tubular echogenic
      thrombus within the retroperitoneum with clot protrusion in the IVC in all cases.
      CT scan and MRI demonstrated ovarian vein thrombosis in all the cases in which it
      was performed but failed to show a mobile thrombus within the IVC in one patient.
      CONCLUSION: Duplex US is a reliable technique to show puerperal ovarian vein
      thrombosis and its extension to the IVC. CT scan and MR imaging can be used to
      precise the extension to the IVC.

PMID- 9757230
TI  - [Retrograde cystography after a first episode of acute pyelonephritis in the
      child and adolescent].
AB  - In spite of its invasiveness, voiding cystourethrography remains the gold
      standard examination for detecting vesico-ureteric reflux. The aim of this study
      was to determine if voiding cysto-urethrography is useful at any pediatric age in
      girls after a first acute pyelonephritis. 152 patients have been retrospectively
      studied. Both reflux frequency and grade progressively decreased according to
      age. Sonography was unable to predict reflux. In more than 3-year-old girls, 8/30
      children with reflux had voiding dysfunction. We suggest clinical and/or a flow
      metric evaluation for voiding dysfunction prior to voiding cystourethrography.
      After 9 years, reflux was so rare that voiding cystourethrography should be
      discussed on an individual basis.

PMID- 9757231
TI  - [CT-guided percutaneous treatment of inoperable pulmonary aspergilloma. Apropos
      of 42 cases].
AB  - The authors report 42 cases of symptomatic pulmonary aspergilloma treated by
      intracavitary percutaneous injections of Amphotericine paste. These patients were
      not considered as operable. The aspergillomas complicated tuberculosis sequels
      and pulmonary fibrosis. Surgery was contraindicated in these patients on account
      of severe respiratory failure. The authors specify the technique for the
      preparation of the paste and for the type of percutaneous injection under CT
      guidance; the aim being to obtain complete filling of the cavity and creating an
      "anaerobic" environment for the aspergillus. The contribution of this technique
      for the non-surgical treatment of patients appears interesting but should be
      carried on a larger series to identify the exact indications and the interaction
      with other treatments (drugs and surgery).

PMID- 9757232
TI  - [MRI cholangiography with rapid spin-echo technique: prospective evaluation of 20
      patients].
AB  - PURPOSE: To evaluate a MR cholangiographic technique using a non breath-hold fast
      spin-echo technique in patients with suspected bile duct obstruction. MATERIAL
      AND METHODS: Twenty patients with suspected bile duct obstruction were
      prospectively investigated with MR cholangiography using a T2-weighted non breath
      hold fast spin-echo technique (TR = 8000-9000 mse, effective TE = 120-266 msec,
      ETL = 16-32, acquisition time = 1-3 min) with a body coil. Results of MR
      cholangiography were compared to those obtained with endoscopic retrograde
      cholangiography (n = 20 patients) and endoscopic sonography (n = 12 patients)
      that were considered as reference. RESULTS: MR cholangiography provided high
      quality images in 19 out of 20 cases (95%). MR cholangiography had 100%
      sensitivity, 100% specificity and 100% accuracy in the diagnosis of bile duct
      dilation. MR cholangiography had 73% sensitivity, 75% specificity and 73%
      accuracy in the diagnosis of bile duct obstruction. MR cholangiography failed to
      depict small stones (< 3 mm) of the main bile duct in 4 cases in which no bile
      duct dilatation was found. CONCLUSION: MR cholangiography using a non breath-hold
      fast spin-echo technique depicts bile duct dilatation with a degree of accuracy
      comparable to that achieved with endoscopic examination. In the absence of bile
      duct dilatation, small stones of the main bile duct may be undetected with MR
      cholangiography.

PMID- 9757233
TI  - [Cavernous dural fistulas: Importance of trans-ocular Doppler ultrasound in
      evaluating venous patency and therapeutic choices].
AB  - Transcranial Duplex scan is a relatively recent diagnostic tool with many
      unexplored clinical potentials. The authors insist on the role of transocular
      exploration, as a non-invasive substitute to angiography and discuss two patients
      with cavernous meningeal arteriovenous fistula, a benign but relatively uncommon
      disease. In the first patient, in whom symptoms recurred, Duplex scan was able to
      rule out thrombophlebitis and to show increased flow in the fistula, thus leading
      to proper treatment. In the second patient, the identification of a periorbital
      thrombophlebitis innocented the fistula and prompted anti-coagulation. We
      conclude that besides its diagnostic capabilities, Duplex scan may be helpful in
      selecting proper treatment and follow-up in specific neurovascular conditions.

PMID- 9757234
TI  - [Focal intrahepatic siderosis, diagnostic pitfall, iatrogenic image].

PMID- 9757235
TI  - [Adventicial cyst of the popliteal artery].
AB  - In a 42-year-old man with intermittent calf claudication, cystic adventitial
      disease of the popliteal artery was demonstrated by 3D CT. Cystic mass was seen
      to be compressing the arterial lumen. The diagnosis of cystic adventitial was
      confirmed by surgery. Compared with color doppler sonography, MR Imaging, 3D CT
      provides additional useful anatomic information concerning disease of the
      popliteal artery, usually gained only with sonography or arteriography.

PMID- 9757236
TI  - [Late perforation of pre-sternal coloplasty: echocardiography diagnosis].
AB  - The authors report a previously non described case of late rupture of a
      presternal colon esophagoplasty in a patient with history of caustic ingestion.
      The role of sonography was the diagnosis of the rupture due to presternal
      position of the coloplasty.

PMID- 9757237
TI  - [What diagnosis? Ureteral pseudodiverticulosis].

PMID- 9757238
TI  - [Interuniversity diploma in cardiovascular imaging: a luxury or a necessity?].

PMID- 9757239
TI  - [Fistulas in chronic hemodialysis].

PMID- 9757240
TI  - [Scientific committee of the French radiology workshops: "how to use"].

PMID- 9757241
TI  - [Role of transcranial ultrasonography in neuroradiological diagnosis].
AB  - Blood flow within the major arteries supplying the brain can be studied with
      transcranial Doppler sonography, a noninvasive, portable procedure. We describe
      the technique of examination, as well as indications in children and adults such
      as the investigation of intracranial stenosis, collateral pathways, vasospasm,
      cerebral emboli and arteriovenous malformations.

PMID- 9757242
TI  - [Radiological expertise and diagnosis. I. Theoretical advances].
AB  - From the cognitive point of view, experts are characterized (1) by the ability to
      directly perceive large meaningful structures due to the development of numerous
      links within their knowledge networks, particularly between categories that, in
      manuals, are described as mutually exclusive (2) by the automation of diagnosis.
      Even in the best experts, some biases remain, mainly due to filters in facts and
      hypotheses selection. These filters are based upon the resemblance of the case
      with prior knowledge, and upon the likelihood of previous encountering similar
      cases. Biases are partially balanced by heuristics which are reasoning processes,
      valid for a majority of cases, but which induce some errors on atypical cases.

PMID- 9757243
TI  - [Radiological expertise and diagnosis. II. Empirical study].
AB  - In order to study cognitive processes of radiological diagnosis, 22 radiologists
      with different experience levels interpreted two complex films, with no clinical
      data. Exploration strategies, used knowledge and reasoning were analyzed.
      Experimented radiologists interpreted clues more easily, using richer and more
      integrated knowledge. They used a symptomatic exploration, guided by hypotheses
      that related to salient cues. Cues that were both subtle and unexpected were
      better detected by novices and "super experts" than by intermediates and "basic
      experts". Novices detected those cues by mean of a systematic exploration. "Super
      experts" benefitted from an increased likelihood of unexpected cue detection due
      to longer and more supported reasoning. Also, they might have complemented the
      symptomatic exploration with an automatic systematic one.

PMID- 9757244
TI  - [MRI diagnosis of sinus cavernous invasion by pituitary adenomas].
AB  - PURPOSE: To evaluate the preoperative MRI criteria of a sinus cavernous invasion
      by a pituitary adenoma. MATERIAL AND METHODS: Study of 102 cavernous sinuses
      among 51 patients who had had a surgical cure of pituitary adenoma. Thirteen
      patients had a surgical invasion of the cavernous sinus. RESULTS: A certain
      number of signs eliminated cavernous sinus invasion. The best means consisted in
      not crossing the intercarotid line (Sensitivity-Se = 100%, Specificity-Sp = 85%
      and Negative Predictive Value-NPV = 100%). The others means implied: not going
      past twelve o'clock on the internal carotid artery-ICA (NPV = 97.1%), symmetrical
      size of the cavernous sinus (NPV = 92.5%), non-convexity of the lateral wall (NPV
      = 90.2%), visualization of at least two venous groups of the laterosellar space
      (NPV = 90.2%) and finally, non-displacement of the ICA (NPV = 89.2%). The best
      criteria for diagnosis were passing by the intra and supracavernous ICA lateral
      tangent (Se = 84.6%, Sp = 95%) and the percentage of ICA encasement by the
      adenoma exceeding 25% (Se = 92.3%, Sp = 85%). CONCLUSION: Except the total
      encasement of the intracavernous ICA, the cavernous sinus can be invaded when the
      lateral tangent of the supra and the intracavernous ICA is crossed, and also when
      the percentage of ICA encasement exceeds 25%.

PMID- 9757245
TI  - [Rare cases of bladder tumors].
AB  - Among epithelial tumors, squamous cell carcinomas represent only 3 to 7% of the
      cases in the temperate countries, but constitute the most frequent histologic
      kind in bilharzien endemic zones and 17% of intradiverticulars tumors. The
      adenocarcinoma is found most often in the bladder dome, representing only 0.3 to
      3% of all bladder tumors. Invasive cancer in a neighboring organ (digestive
      tract, genital organs) must be eliminated. In most cases, combining
      ultrasonography and intravenous urography can be helpful for diagnosis of
      intradiverticular carcinoma or bladder dome tumor. Computed tomography and
      magnetic resonance images are the best methods for positive diagnosis and
      extension exploration for tumors of the dome and base of the bladder. In this
      work, we report a series of five cases of uncommon bladder carcinoma. Three of
      the cases were intradiverticular squamous cell tumors and two were adenocarcinoma
      of the bladder dome.

PMID- 9757246
TI  - [Percutaneous recanalization of proximal venous thromboses in chronic
      hemodialysis patients].
AB  - Occlusion of the proximal vein in chronic hemodialysis patients results in vein
      hypertension and a "swollen arm". The usual treatment for this "swollen arm"
      consists in closing up the fistula and making another access on the contralateral
      member. But this is not always possible and, with some patients, recanalization
      is the only solution. We have performed 4 recanalizations successfully: 2
      accesses remain permeable after 10 and 24 months, another patient needed to be
      fitted with two endoprosthesis just after recanalization and access, in his case,
      remained permeable until he died of intestinal ischemic syndrome six months
      later. The fourth patient presented a reocclusion two months later but could not
      be reoperated on because of bad general state of health. An attempt to perform
      recanalization on a fifth patient was a failure. Such results show that
      recanalization of a thrombosed proximal vein is worth attempting before closing
      access for good.

PMID- 9757247
TI  - [Synovial sarcoma localized in the muscles].
AB  - We report three cases of synovial sarcoma strictly located in the muscles.
      Synovial sarcoma generally arises in the vicinity of joints, tendon sheaths,
      bursae, fascia, and ligaments. Strictly intramuscular locations are not well
      known and not described in the literature to our knowledge although they seem to
      be frequent. The different characteristics on the radiographic examinations are
      non specific, and this location may be misleading. MRI is considered the
      procedure of choice for staging this tumor and to visualize soft tissues and bone
      invasion. CT scans may be useful in detecting more specific small calcifications.

PMID- 9757248
TI  - [Bladder herniation in a inguinal-scrotal hernia complicated by acute renal
      insufficiency].
AB  - We report one case of massive inguino-scrotal bladder herniation which was
      responsible for an acute obstructive renal insufficiency. The different types of
      bladder hernias and their anatomic factors are described. The clinical
      radiological findings and surgical management are discussed.

PMID- 9757249
TI  - [Abnormality of hepatic perfusion in superior vena caval obstruction syndrome. A
      case report diagnosed by CT scan].
AB  - We describe a case of focal and intense contrast enhancement on hepatic CT due to
      superior vena caval obstruction and brachiocephalic vein obstruction. This
      phenomenon is explained by systemic portal venous shunting.

PMID- 9757250
TI  - [Post-traumatic intrasplenic arteriovenous fistula in a child. Spontaneous
      regression].
AB  - We report on an 11-year-old boy who developed splenic arteriovenous fistula
      resulting from blunt abdominal trauma. This fistula disappeared spontaneously
      after 8 months of follow-up without any complication.

PMID- 9757251
TI  - [Magnetic resonance imaging of multiple myeloma].

PMID- 9757252
TI  - [Diagnostic and prognostic value of magnetic resonance imaging in multiple
      myeloma: the clinician's point of view].

PMID- 9757253
TI  - [Value of high-frequency ultrasonography (20MHz) in the diagnosis of cutaneous
      tumors].

PMID- 9757254
TI  - [Can we optimize radioprotection for medical workers?].
AB  - Implementation of the principle of optimization (ALARA), an essential radiation
      protection regulations, remains very limited in the medical field, even though
      80% of workers whose exposure exceeds 50 mSv are to be found in this domain. The
      doses measured by legal dosimetry sometimes underestimate the real exposure of
      workers. It is therefore necessary to optimize the protection of occupational
      exposure in the medical field. This paper reviews the steps of the optimization
      procedure with emphasis on specificity of its application in this domain.
      Operational dosimetry as well as information on the residual risk due to low
      exposures and a better estimation on the risk/benefit factor for the patient are
      needed for satisfactory implementation.

PMID- 9757255
TI  - [Value of high-frequency (20 MHz)in the diagnosis of cutaneous tumors].
AB  - The purpose of the present study is to asses the value of high frequency
      ultrasonography (20 MHz), a new noninvasive imaging technique, in cutaneous
      tumors. Cutaneous tumors are clinically varied and their diagnosis is still based
      on histopathological analysis. 140 cutaneous tumors have been examined with US
      and imaging findings have been compared to the results of clinical and
      histological examinations. This study shows that high frequency ultrasonography,
      even though it cannot replace pathological analysis, may help the dermatologist
      in the positive diagnosis of some cutaneous tumors and in accessing the location
      and the in depth-extension of the lesions in the different layers of the skin.

PMID- 9757256
TI  - [Digital image processing of screening mammographies: application to masses].
AB  - A method based on image processing of tumoral neighbourhood is described for
      studying masses. By using polar and pseudopolar representations for the tumor and
      its neighbourhood, it is possible to detect divergent structures around the
      lesion and to evidence fuzzy areas in the boundary of the tumor, which constitute
      two significant features of breast cancer. The degree of spiculation is deduced
      from a shape parameter that characterizes the irregularity of the boundary; the
      radial component of the gradient on the boundary provides a measurement of fuzzy
      appearance.

PMID- 9757257
TI  - [Renal insufficiency with AIDS: ultrasonographic aspects].
AB  - Renal pathologic changes in AIDS involve various factors and can also occur in
      several other forms of renal disease. Renal sonography was prospectively
      performed in 31 patients with laboratory evidence of AIDS and renal
      insufficiency. All patients included in this study were without clinical
      manifestations (group II of the CDC) and without risk factors of AIDS. AIM: to
      characterize renal pathologic changes underlying the sonographic findings in
      these patients. Sonographic evaluation included determination of renal sizes and
      renal echogenicity according to standard grading system. Sonography showed normal
      sized or enlarge-sized kidneys. Enlarged kidneys were generally due to increased
      thickness rather than length or width; small-sized kidneys were not observed.
      Grading echogenicity showed: grade 0 in 3 patients, grade I in none, grade II in
      11 patients and grade III in 17 patients. In six patients, we found "spotted"
      echostructural figure due to several hypoechoic and rounded zones. Echogenicity
      increased with the severity of renal insufficiency. Our study suggests that renal
      abnormalities are varied and can occur in all stages in the course of the
      disease. The particular "spotted" figure associated with enlarged size at the
      expense of thickness of kidneys must draw radiologist's attention to the
      probability of AIDS lesions. Further studies with large populations must be
      performed to confirm our observations.

PMID- 9757258
TI  - [CT x-ray evaluation of abdominal and pelvic veins in patients suspected of acute
      pulmonary embolism with negative Doppler sonography].
AB  - PURPOSE: To address prospectively the potential of CT of the abdomen and pelvis
      to demonstrate deep vein thrombosis in patients suspected of acute pulmonary
      embolism and investigated with helical CT of the pulmonary arteries. MATERIAL AND
      METHODS: 197 patients presenting non-diagnostic scintigraphy and negative Doppler
      US of lower limbs and IVC were included. They had helical CT of the pulmonary
      arteries (5mm collimation, 1:1 pitch, reconstruction every 2.5 mm, injection of
      120 mL of contrast media at a rate of 3 mL/sec). Ninety seconds after the end of
      the thoracic acquisition, abdominal and pelvic CT were acquired (7 mm collimation
      every 12 mm). RESULTS: 3 (1.5%) of 197 patients had an unknown thrombosis of the
      caval system (renal vein, ovarian vein, lilac veins). A fourth patient had an
      unknown thrombosis of the mesenteric vein. All these patients had a pulmonary
      embolism (4/40). None of the 157 patients without pulmonary embolism at helical
      CT showed deep venous thrombosis. CONCLUSION: In our study, CT of the abdomen and
      pelvis disclosed an unknown thrombosis of a deep vein of the abdomen and pelvis
      that can explain the pulmonary embolism in 7.5% of patients.

PMID- 9757259
TI  - [Image quality and optical density in mammography: study on phantoms].
AB  - Optical densisty (od) is an important factor for image quality in mammography. We
      studied the effect of o.d. on the image score with two phantoms (Contrast Detail
      MAMmography phantom (CDMAM), University Hospital Nijmegen, The Netherlands and
      breast-equivalent phantom (MTM 100) made by CIRS in the United States). We also
      evaluated the doses required to obtain the blackening considered from
      measurements made with thermoluminescent pastilles. Two series of exposure were
      performed at 28 kV with mAs ranging from 25 to 100 to obtain a range of o.d.
      varying between 0.72 and 2.67. Image scores were then evaluated for each negative
      by calculating the mean of five different readers. The study showed a clear
      increase of the image score with o.d. These observations were consistent with
      other studies. For the two phantoms and the screen-film combination used, the
      maximum quality was obtained for an o.d. of 1.6, but the drawback of negatives at
      high o.d. is increase of the irradiation dose from 5,4 to 7,2 mGy when the o.d.
      increases from 1.30 to 1.70.

PMID- 9757260
TI  - [Inflammatory spondylodiscitis as a unique radiological manifestation of the
      SAPHO syndrome].
AB  - We describe two cases of SAPHO with an exclusive spinal involvement. Diagnosis
      was established by sterno-clavicular arthralgias, palmar and plantar pustulosis
      and by radiological signs of inflammatory spondylodiscitis and vertebral
      osteitis. Spondylodiscitis and medullary edema resolved as shown by MRI after
      administration of steroids in one case and methotrexate in the other.

PMID- 9757262
TI  - [Spontaneous hyperintensity of the anterior pituitary gland in MRI T1-weighted
      images related to manganese deposits in a patient undergoing prolonged parenteral
      nutrition].
AB  - The signal abnormalities found on MRI in the basal ganglia in patients with an
      increased plasmatic level of manganese are well known. We report a case with a
      hyperintense signal in a patient with a high plasmatic level of manganese due to
      long term parenteral nutrition. The normal signal intensity of T2-weighted
      imaging in the anterior pituitary gland helps to differentiate the increased
      signal intensity of T1 weighted imaging due to deposition of manganese from
      hemorrhagic or fatty lesions.

PMID- 9757261
TI  - [Regression of a focal nodular hyperplasia after stopping oral contraceptives].
AB  - The complete regression of a focal nodular hyperplasia of the liver with typical
      MRI patterns 5 years after withdrawal of oral contraceptives was observed.
      Effects of oral contraceptives on this tumor's evolution and appropriate imaging
      by MRI are discussed.

PMID- 9757263
TI  - [A rare mediastinal-hilar pseudotumor: esophageal and azygos vein varices].
AB  - Mediastinal pseudotumors are present in less than 5% of patients with long
      standing portal hypertension. These pseudotumors may be caused by para-esophageal
      collateral vessels or greatly dilated azygos or hemiazygos veins. Enhanced CT
      seems to be the best tool for the diagnosis and in evaluating the overall status
      of portosystemic collateral vessels. In this case report, MRI ruled out tissular
      mass by showing vascular signal.

PMID- 9757264
TI  - [What is it? Bilateral sacroilitis and avascular necrosis of the left hip in
      Crohn's disease treated with corticoids].

PMID- 9757265
TI  - [Conventional digital radiology and development of the level of images].

PMID- 9757266
TI  - [And if this was not one's profession. Their medicine to them, my medicine to
      me].

PMID- 9757267
TI  - [MRI and articular cartilage].
AB  - Although plain films are fundamental for routine imaging of degenerative chondral
      lesions, MRI is a promising tool of investigation for the articular cartilage.
      Its modalities are still imprecise and debated, but, because of its
      noninvasiveness, it is destined to be preferred over arthroCT. The small size of
      the cartilage requires thin slices of less than 3-mm thick. The various features
      of normal cartilage images must be well known. They depend on acquisition
      parameters, zonal structure of the cartilage and numerous artifacts (partial
      volume average, chemical shift, magnetic susceptibility, truncation, "magic
      angle"). Fast SE images provide a good compromise between contrast and the signal
      to-noise ratio. T2-weighted images take advantage of an arthrographic effect in
      case of joint effusion. 3D GE images allow a more accurate evaluation with 1-mm
      thick slices. In all sequences, adding of a fat-suppression presaturation
      increases contrast between the cartilage and the surrounding structures. The
      diagnostic accuracies of the different sequences and of MR arthrography are
      discussed. Quantitative measurements of cartilage thickness and volume remain the
      topic of clinical research.

PMID- 9757268
TI  - [MRI study of the arterial ligament and the left pulmonary artery in the
      preoperative staging of left upper lobe bronchial cancers].
AB  - PURPOSE: To demonstrate that the ligamentum arteriosum is visible by precisely
      oriented MRI. To demonstrate the predictive value of the ligament involvement for
      left upper lobe cancer surgery. MATERIAL AND METHODS: Fifteen controls, age
      matched with bronchial cancer patients, were studied to establish how the
      ligamentum arteriosum could best be visualized on MRI. Visibility was optimal on
      RASE T1-weighted sequences on the frontal and sagittal oblique planes (aorto
      pulmonary window). Acquisitions were performed with a body coil, 7 mm slices, 480
      mm Fov, on a Magnetom Expert, 1T Siemens machine. Forty five patients with left
      upper lobe cancer underwent MRI investigation after CT had shown mediastinal
      proximity of the left pulmonary artery and the tumor. They underwent surgery with
      manual localization of the ligament at the beginning of the procedure. Findings
      and operative decisions were compared with those of MRI, establishing its
      predictive value. MRI defined the tumor-ligament and tumor first centimeters of
      the left pulmonary artery (LPA) relationships. RESULTS: MRI ligamentum visibility
      was about 87%. Ligament non-involvement on MRI (n = 23) was confirmed at surgery
      in all cases (100% concordance). Involvement suggested on MRI was confirmed in 18
      cases and surgery was impossible or unsatisfactory. There were four false
      positives with successful surgery (8% false positives). CONCLUSION: When CT shows
      left lobe cancers extending in the mediastinum towards the LPA, precisely
      oriented MRI assesses surgical difficulty and resectability by demonstration
      involvement of the ligamentum and the first two centimeters of the LPA.

PMID- 9757269
TI  - [Hepatocellular carcinoma (HCC) observed in Abidjan: aspects and role of
      ultrasonography].
AB  - In this retrospective study, we define the localization and ultrasound
      appearances of hepatocellular carcinomas observed in Abidjan. The study included
      31 inpatients (23 males and 8 females), aged from 24 to 76 years (mean, 47.4).
      All patients had serum alphafetoprotein dosage and 21 patients had cytologic
      examination. Diagnosis was based on a high level of serum alpha-fetoprotein (>
      500 ng/ml), with or without cytological proof. Tumor characteristics (size,
      number, echogenicity, nodular or diffuse form) and associated extratumoral signs
      were noted. Ultrasound identified 19 cases of small tumors (size < 5 cm), and 12
      large tumors (size > or = 5 cm). The tumor forms were mostly nodular and multiple
      (24 cases), solitary nodule (3 cases), diffuse or infiltrative (4 cases). The
      liver was heterogeneous with hyperechoic tumoral nodules (16 cases), hypoechoic
      tumoral nodules (5 cases), hyperechoic and diffuse form (4 cases), and 2 cases of
      mixed form. We have noted a particular form in 4 cases represented by a
      heterogeneous liquid-like mass simulating tropical abscesses. Ascites (12
      patient) was the most common extratumoral sign. Portal vein invasion or thrombus
      was rare (3 patients). Of the 31 patients, ultrasound was abnormal in all cases,
      alpha-fetoprotein test was positive in 12 cases (57.14%) and negative in 9 cases
      (42.8%). Cytological test was positive in 17 cases (80.95%), and negative in 4
      cases (19.04%). Alphafetoprotein and cytologic tests were both positive in 8
      cases and, nonconcordant in 13 cases; in 4 cases alphafetoprotein was positive
      while cytological tests were negative and, in 9 cases alphafetoprotein was
      negative while cytological tests were positive. Two negative tests were never
      observed. In Abidjan, hepatocellular carcinomas are commonly small or large,
      multinodular and hyperechoic tumors contrasting with the small nodular and
      hypoechoic tumors usually reported in western series. Ultrasound associated with
      cytologic examination, appears to us to be more usefulness than alphafetoprotein
      dosage in the diagnosis of hepatocellular carcinoma.

PMID- 9757271
TI  - [MRI in post-traumatic cerebral fat embolism].
AB  - We report two cases of posttrauma cerebral fat embolism evaluated with MRI. Due
      to sensitivity, MRI is the best examination for detecting focal abnormalities of
      the grey or white matter. MRI helps to make the diagnosis in atypical cases and
      allows assessment of both extension and course of the embolism.

PMID- 9757270
TI  - [Single shot fast spin echo sequence MRI cholangiopancreatography].
AB  - PURPOSE: To assess the value of single shot fast spin echo MR sequence (SS-FSE)
      in the morphological analysis of the biliary tree and pancreatic ducts and to
      compare its accuracy with other imaging methods. MATERIAL AND METHODS: 95
      consecutive patients referred for clinical and/or biological suspicion of biliary
      obstruction were explored with MR cholangiopancreatography (MRCP). All patients
      were explored with a Signa 1.5 T GE MR unit, with High Gradient Field Strength
      and Torso Phased Array Coil. Biliary ducts were explored with SS-FSE sequence,
      coronal and oblique coronal 20 mm thick slices on a 256 x 256 matrix. Total
      acquisition time was 1 second. Native pictures were reviewed by two radiologists
      blinded to clinical information. In case of disagreement, a third radiologist's
      judgement was requested. In 88 cases, MRCP results were compared with direct
      biligraphy methods. RESULTS: In all cases, MRCP produced high quality images
      without MIP or other post-processing methods. For detection of biliary tree
      distensions, the concordance value of MRCP was over 91% (Kappa 0.82). For
      detection of biliary tree and/or pancreatic duct obstruction, MR sensitivity was
      100% and specificity 91%. The overall diagnostic concordance value of MRCP was >
      or = 93%. Difficulties in MRCP were caused by functional diseases or benign
      stenosis. MRCP accurately diagnosed all lithiasic obstructions starting from a
      stone size of 3 mm. CONCLUSION: MRCP produces fastly high-quality images. As it
      is totally safe, it can be proposed as a first intention method in
      biliopancreatic duct explorations.

PMID- 9757272
TI  - [Mesenteric lymph node cavitation disclosing celiac disease in adults].
AB  - We report a case of cavitation of the mesenteric lymph nodes, an uncommon
      complication of celiac diseases. Computerized tomography is the method of choice
      for diagnosis and follow up after gluten free diet.

PMID- 9757273
TI  - [Aberrant origin of the splenic artery].
AB  - We report an incidental finding of an aberrant origin of the splenic artery
      described here for the first time.

PMID- 9757274
TI  - [Ameloblastic carcinoma. Apropos of a case].
AB  - Ameloblastic carcinoma is an exceptionally rare odontogenic tumor. Ameloblastoma
      is considered malignant if there is evidence of metastasis or histological
      features of malignancy. Present classification of these tumors is debated.
      Several authors use the term malignant ameloblastoma for tumours that metastasize
      despite "benign" histological features whereas ameloblastic carcinoma is referred
      to as a tumor with malignant histological features regardless of its metastatic
      potential. We report a case of mandibular ameloblastic carcinoma with cervical
      lymph node metastasis in a 70-year-old man, documented by MRI and CT. We discuss
      current knowledge on these tumors.

PMID- 9757275
TI  - [What is it? The periportal halo sign in primary biliary cirrhosis].

PMID- 9757276
TI  - [Recurrent chronic multifocal osteitis in children].

PMID- 9757277
TI  - [Pulmonary embolism: the radiologist on the alert].

PMID- 9757278
TI  - [Iodinated contrast media].

PMID- 9757279
TI  - [Does a universal strategy of acute pulmonary embolism diagnosis exist today?].
AB  - In this review, we demonstrate that there is no universal diagnostic strategy for
      non-severe acute pulmonary embolism. The first part of the article is devoted to
      the concept of thromboembolic disease: its frequency, severity and diagnostic
      difficulties. The second part analyzes the tools used for diagnosis of pulmonary
      angiography, noninvasive venous studies, and helical CT angiography. The last
      part discusses current diagnostic algorithms for pulmonary embolism and the
      changes that may be introduced by the use of helical CT in clinical practice. The
      potential for MR imaging id discussed.

PMID- 9757280
TI  - [Comparative value of MR-angiography, helical CT and digital angiography in the
      preoperative assessment of abdominal aortic aneurysms].
AB  - PURPOSE: To compare helical CT with MR angiography in pre-operative assessment of
      abdominal aortic aneurysm (AAA). MATERIAL AND METHODS: Twenty patients with AAA
      underwent helical-CT, MR-angiography and digital angiography. All exams were
      interpreted independently by two groups of observers. Kappa and rho were
      calculated to assess correlations. Sensitivity and specificity were calculated to
      compare each method with the "gold standard" digital angiography. RESULTS: Inter
      observer correlation was excellent. There was a very good agreement between both
      methods in the assessment of the maximal diameter and the proximal neck of the
      aneurysm. There was no significant difference in the assessment of stenoses of
      the visceral and iliac arteries, the number of renal arteries, and iliac
      extension. CONCLUSION: Helical CT and MR angiography are equivalent in pre
      operative assessment of AAA.

PMID- 9757281
TI  - [MRI semeiology of segmental contraction abnormalities in arrhythmogenic
      dysplasia of the right ventricle].
AB  - The diagnosis of localized arrhythmogenic right ventricular dysplasia may be
      difficult to ascertain. Aside from electrophysiological arguments, visualization
      of an abnormal right ventricular contraction pattern is of crucial importance for
      diagnosis. Cine-MR is almost the only examination method which offers detailed
      informations on the right ventricular contraction pattern. Nine observations of
      segmental right ventricular contraction abnormalities assessed by cine-MR are
      described here: dyskinesia of the distal part of the anterior wall (2), of the
      inferior wall (2), of the right ventricular outflow tract (2); akinesia of the
      outflow tract (2) and of the inferior wall (1). Morphological abnormalities of
      the right ventricle are always associated with contraction abnormalities but seem
      to be less disease specific. Patients should be more readily referred for a cine
      MR examination when the diagnosis of localized right ventricular dysplasia is
      suspected. Cine-MR sequences related to these observations may be reached via
      Internet at:http:@alsace.u-strasbg.fr/cardio/coeur.htm.

PMID- 9757282
TI  - [Ultrasonography of dorsal elastofibroma. Apropos of 6 cases].
AB  - Elastofibroma dorsi is a benign soft-tissue tumor. Its sub- and pre-scapular
      location and its appearance on CT and MRI generally lead to the diagnosis. We
      have analyzed with sonography 6 elastofibromas in 4 patients; the diagnosis was
      confirmed with CT scan or MRI. Some sonography imaging features supported the
      diagnosis of elastofibroma dorsi. In all the cases, (1) the tumor occurred
      typically in a sub- and pre-scapular location, and (2) showed a streaky
      echostructure (3). A similar symptomatic or asymptomatic mass in the opposite
      subscapular location is highly suggestive.

PMID- 9757283
TI  - [Inflammatory pseudotumors of the liver. Apropos of a pediatric case with
      radiological and ultrasonographic features and anatomopathological correlations].
AB  - Inflammatory pseudo-tumor of the liver (IPT) are benign encapsulated masses. IPT
      or inflammatory myofibroblastic tumor is a myofibroblastic proliferation with
      chronic inflammatory cell infiltration of unknown origin. A four-year-old girl,
      with cutaneous flushing of the face and biological inflammatory syndrome was
      referred for abdominal investigation. Ultrasound examination showed a 5-cm mass
      located in the anterior segment of the right hepatic lobe. After abdominal CT
      showing slightly vascular feature of this right hepatic mass, diagnosis was made
      through percutaneous US-guided fine needle biopsy. Surgical resection was
      performed and pathologic examination of the mass confirmed preoperative
      diagnosis. Clinical outcome was good.

PMID- 9757284
TI  - [Subcutaneous trochanteric bursitis: an unrecognized cause of peritrochanteric
      pain revealed by imaging].
AB  - We present four cases of subcutanea trochanterica bursitis (one involving both
      sides). The bursitis was acute and inflammatory in two cases, chronic and
      microtraumatic in one, asymptomatic in one and septic in the last case. The
      acutely inflamed bursa may contain a blood effusion increasing the pain. CT and
      MRI provide distinctive images for the diagnosis of these particular types of
      periarticular diseases.

PMID- 9757285
TI  - [Multiple calcified cerebral metastases revealing bronchial adenocarcinoma.
      Apropos of a case].
AB  - Calcified brain metastases are rare. They are unique or multiple. The primary
      site is lung, breast, gastro-intestinal tract, uterine cervix, bone or may be
      unidentified. It corresponds pathologically to an adenocarcinoma, a sarcoma or to
      a squamous cell carcinoma. We report a case of multiple calcified brain
      metastases discovered before primary tumour (bronchial adenocarcinoma), raising
      the problem of differential diagnosis resolved by stereotaxic brain biopsy.

PMID- 9757286
TI  - [Epidural air after closed thoracic trauma].
AB  - We report a rare case of spontaneous pneumorachis (epidural air in the spinal
      canal) after benign chest trauma without rib fracture or pneumothorax.

PMID- 9757287
TI  - [Quid? Bilateral renal angiomyolipoma (AML) revealing Bourneville's tuberous
      sclerosis (BTS)].

PMID- 9757289
TI  - [News of the SIGU (Societe d'Imagerie Genito-Urinaire)].

PMID- 9757288
TI  - [Contribution of Abdoscan in MRI cholangio-pancreatography and MRI urography].
AB  - MR Cholangiopancreatography (MRCP) and MR Urography (MRU) are promising recent
      imaging modalities. Oral magnetic particles (Abdoscan, Nycomed SA, Oslo, Norway)
      is an oral negative contrast agent eliminating signal intensity of the gastro
      intestinal tract thus improving image quality at MRCP and MRU.

PMID- 9757290
TI  - [Radiology assessment: the European dimension].

PMID- 9757291
TI  - [Economic assessment in radiology].

PMID- 9757293
TI  - [Prenatal MRI of corpus callosum agenesis. Study of 20 cases with
      neuropathological correlations].
AB  - Twenty prenatal MR studies of corpus callosum agenesis were retrospectively
      studied and compared with neuropathologic examinations (18) or postnatal imaging
      (2). Corpus callosum agenesis were either complete (14) or partial (6). Positive
      diagnosis was made in 19 cases/20. The diagnosis of "isolated" or "associated"
      corpus callosum agenesis was assessed in 11 cases/15. MR depicted 15 of the 33
      associated neurologic abnormalities. Prenatal MR is a valuable complementary
      technique for the diagnosis of corpus callosum agenesis when sonography is
      doubtful. MR could improve prognosis evaluation, since it enables depiction of
      associated abnormalities, notably gyral abnormalities, posterior fossa
      malformations, and intra-cranial cysts. MR images prove to be useful before
      neuropathologic examinations.

PMID- 9757292
TI  - [Ductal carcinoma in situ of the breast: role of imaging].
AB  - The incidence of ductal carcinoma in situ (DCIS) has increased with the
      widespread use of screening mammography. DCIS is often suspected when clustered
      microcalcifications are evidenced on routinely performed mammography. High
      quality mammographies are required and should be completed with magnification
      views. Mammographic--pathologic correlations are described according to the new
      classifications as well as unusual forms of presentation on mammography. Early
      contrast enhancement in DCIS on dynamic MRI is reported and seems to be related
      with angiogenesis. A wire localization procedure of non-palpable lesions has to
      be performed and per-operative specimen radiography is mandatory. Stereotaxic
      large core needle biopsy is a valuable alternative to surgical biopsy but a
      multidisciplinary team approach is necessary and follow-up is recommended if no
      excisional biopsy is done. Quality in the management of DCIS depends on the
      coherence of the "multidisciplinary team".

PMID- 9757294
TI  - [Primary epiploic appendicitis].
AB  - Primary epiploic appendicitis include torsion and primary inflammation of
      appendices epiploicae. These uncommon pathologies have been until present
      exceptionally diagnosed before surgery. Clinical and biological features have a
      small specificity. However, US and CT findings suggest the diagnosis. Our study
      reports 6 cases.

PMID- 9757295
TI  - [Contribution of fast-sequence three-dimensional MRI angiography with Gadolinium
      injection in the evaluation of supra-aortic vessels].
AB  - Sixty-nine patients with cervical atherosclerotic disease were evaluated by
      Magnetic Resonance (MR) angiography using a coronal 3D gradient echo gadolinium
      enhanced sequence. The image quality was evaluated for each artery and ostium on
      MIP reconstructions. A comparison with conventional angiography was achieved in
      27 patients. All MR examinations were assessable; a second injection was
      performed in ten patients. All carotid bifurcations were visualized. The ostium
      of the common carotid artery was not assessable in 44% of cases due to the
      limited coverage. The evaluation of the posterior circulation was good in 90% of
      cases. The agreement between MR angiography and conventional angiography was good
      despite a tendency to overestimate moderate stenoses. Stenoses greater than 70%,
      carotid occlusions and vertebral stenoses greater than 50% were correctly
      detected.

PMID- 9757296
TI  - [A rare etiology of abdominal calcifications: lithopedion].
AB  - We report a case of a rare and particular cause of abdominal calcifications
      represented by the lithopedion. We describe different radiologic appearances
      observed by: abdominal plain film, echography and CT. It appeared to us that
      abdominal plain film alone is sufficient for diagnosis and undertaking surgery.
      Echography and CT are helpful, especially for complementary evaluation.

PMID- 9757297
TI  - [Ganglion cyst of the cervical spine causing radiculopathy].
AB  - A case of ganglion cyst of the cervical spine causing radiculopathy is presented.
      This epidural mass is rare at the cervical level. Computed tomography suggests
      the diagnosis by the postero-lateral position of the mass close to facet joint.
      The trilobed configuration and the tissue characterisation of the cyst are well
      documented on MRI.

PMID- 9757298
TI  - [Recurrent stomal hemorrhage treated by transjugular intrahepatic portosystemic
      anastomosis and embolization of stomal varices].
AB  - Bleeding stomal varices is a rare complication of portal hypertension. We report
      the case of a cirrhotic patient, with a history of colonic adenocarcinoma, who
      had recurrent bleeding stomal varices. Treatment with transjugular intrahepatic
      portosystemic shunt and stomal varice embolization was performed because failure
      of medical treatment of portal hypertension and sclerotherapy. Twenty six months
      later only one stomal hemorrhage was noted. This suggests that transjugular
      intrahepatic portosystemic shunt and stomal varice embolization is effective in
      case of recurrent bleeding of stomal varices.

PMID- 9757300
TI  - [Computed tomography in the management of lymphomas].

PMID- 9757299
TI  - [Quid. Aorto-caval fistula in abdominal aortic aneurysm with clotting of the
      supra-aneurysmal inferior vena cava].

PMID- 9757301
TI  - [Impact factor: what for?].

PMID- 9757302
TI  - [Bibliometric index].
AB  - The Institute of Scientific information has edited an index to evaluate the
      diffusion of scientific articles. It is based on the fact that the more an
      article is cited as a reference in other articles, the more it is considered to
      be important, and the higher the coefficient attributed to the journal in which
      it was originally published. The impact factor takes into account the average
      number of times which a journal is mentioned for recent articles published in a
      given year. This index is an attempt to quantify the notoriety of scientific
      journal for all scientific medical specialties.

PMID- 9757303
TI  - [Magnetic resonance angiography of the carotid artery: artifacts, anatomy,
      diseases].
AB  - Magnetic resonance angiography is now a technique commonly used in neurologic
      practice. We give a brief overview of the biophysical principles of this
      technique. Recent refinements and technical innovations are also noted. After
      some anatomic considerations about the carotid artery, we provide some data about
      the role of MRA in atherosclerotic and non atherosclerotic diseases (dissections,
      aneurysms, arteritis, post operative follow-up...) of the extra and intracranial
      carotid arteries. The purpose of this review is to concentrate on the role of
      magnetic resonance angiography in patients with various carotid artery diseases
      and to specify possibilities, limitations and risk of misinterpretation. Magnetic
      resonance angiography is a major, still evolving technique.

PMID- 9757304
TI  - [Study of cotyloid anteversion by coxometric measurement].
AB  - A coxometric evaluation is helpful for the diagnosis and the prognosis of hip
      dysplasia. These measurements also given an intrinsic guide to the surgeon for
      total hip arthroplasty. A coxometric protractor is drawn on the majority of the
      goniometers and allows the measurement of the angle of internal and external
      roof, the angle of the acetabular roof obliquity and the femoral neck-shaft angle
      on a hip AP X-ray. The purpose of this report is to demonstrate that on the same
      X-ray, the adequate placement of the coxometric protractor allows to calculate
      the inclination angle, the acetabular anteversion angles and the anterior roof
      angle.

PMID- 9757305
TI  - [Computed tomography of intrahepatic pancreatic pseudocysts].
AB  - PURPOSE: Intrahepatic pseudocyst complicating pancreatitis is a rare event. The
      goals of this paper are to report the computed tomographic (CT) features of
      intrahepatic pseudocyst and to analyze the role of percutaneous puncture and
      percutaneous drainage in the diagnosis and treatment of intrahepatic pseudocyst.
      MATERIAL AND METHODS: Three cases of intrahepatic pseudocyst studied by CT were
      retrospectively reviewed. Percutaneous puncture of the intrahepatic pseudocyst
      was performed in two cases, and was subsequently followed by percutaneous
      drainage of the intrahepatic pseudocyst in one case. RESULTS: In the three cases,
      intrahepatic pseudocysts appeared like multiple, hypoattenuating, homogeneous
      intrahepatic fluid collections, associated with intrahepatic bile duct dilatation
      in one case. In the two cases in which it was performed, percutaneous puncture of
      the pseudocyst revealed an elevated amylase level, thus confirming the diagnosis.
      In one case, percutaneous puncture revealed superinfection, thus indicating
      percutaneous drainage of the pseudocyst. CONCLUSION: The diagnosis of
      intrahepatic pseudocyst should be suggested in the presence of pancreatic lesions
      and a single or multiple intrahepatic fluid collections visible on CT. CT allows
      percutaneous puncture of the pseudocyst to be done, thus confirming the diagnosis
      and indicating subsequent performance of percutaneous drainage in complicated
      cases.

PMID- 9757306
TI  - [MRI and bladder leiomyoma].
AB  - Unlike epithelial tumors, connective tissue tumors are uncommon, representing
      only 3% of all bladder tumors. Leiomyoma of the bladder is the most frequent non
      epithelial benign tumor of the bladder. Magnetic resonance imaging (MRI) is
      highly useful for diagnostic purposes and to determine the degree of extension.
      Only few reports of sonographic findings have been reported for leiomyoma of the
      bladder. The tumor usually develops within the bladder. Extravesicular formations
      have also been reported as well as a few intramural localizations. The
      characteristic feature is the absence of mucosal involvement. We analyzed the MRI
      findings in a case of leiomyoma of the bladder with intra and extravesicular
      development, inflammatory reaction of the bladder wall and uterine adherences in
      a woman with a past history of chronic cystitis. The role of diagnostic MRI is
      discussed.

PMID- 9757308
TI  - [Intracranial metal foreign bodies and contraindications of MRI. Apropos of a
      case].
AB  - We report a firearm wound of the brain which could not be analyzed by computed
      tomography because of induced artifacts. MRI study was remarkably after verifying
      the non-ferromagnetic nature of the projectiles.

PMID- 9757307
TI  - [Renin-secreting tumor detected by MRI].
AB  - We report an uncommon case of small renin secreting tumor of the kidney located
      in the medulla. The tumor was primarily detected by MRI and subsequently studied
      by spiral CT. The results and limitations of both techniques are discussed.

PMID- 9757309
TI  - [Malignant melanoma of soft tissues. Apropos of a case].
AB  - A case of malignant melanoma of the quadriceps tendon is reported. This is an
      uncommon soft tissue sarcoma of melanocytic origin. The appearance on MRI depends
      on its melanin content. The microscopic appearance is distinctive and prognosis
      is poor. This tumor should be kept in mind when a nodular lesion is detected in
      specific tendon or aponeurosis.

PMID- 9757310
TI  - [Quid? Hepatic distomatosis at the invasive phase].

PMID- 9757311
TI  - [Slice thickness of spiral CT images as function of pitch].
AB  - This report comments on several measures of effective slice thickness. In
      particular, the full width at half maximum FWHM of the slice sensitivity profile
      is discussed. An analytical approximation between FWHM and the pitch p is
      established. Values of FWHM are compared as a function of pitch from the
      approximate formula, from an empirical formula, from an exact calculation and
      from measurements. In addition, the approximation for the full width at tenth
      maximum is also given and is compared with exact calculations. The main results
      of this investigation is that the analytical formulae, although approximate, are
      sufficiently precise and easy to use.

PMID- 9757312
TI  - [Meningeal hemangiopericytomas. A retrospective reciew of 20 cases].
AB  - BACKGROUND AND PURPOSE: Meningeal hemangiopericytomas (MHP) account for 2% of
      meningeal tumours. Clinical features, radiology findings, therapy and outcome of
      20 MHP operated in our department from 1965 through 1995 were analyzed to
      determine presurgical features for diagnosis, histologic diagnostic criteria and
      the role of adjuvant post-operative radiotherapy. METHODS: In conformity with the
      new WHO classification which differentiates MHP from meningiomas, 20 patients
      with tumors compatible with this definition were reviewed. RESULTS: The clinical
      features differed slightly from meningiomas. Only epidemiologic data were
      different. The CT and MRI scanning gave no preoperative distinction between MHP
      and meningiomas. Angiography played a predominant role in this distinction. The
      20 patients were operated. Twelve received post-operative radiotherapy. The rate
      of local recurrency was 45%. Of these, 88% did not receive radiotherapy post
      operatively. Two patients (10%) presented late recurrence and three patients
      (15%) one or more extra-neural metastases. Two patients received radiosurgical
      treatment. In one case with disseminated metastasis, chemotherapy was used
      without success. Three patients died during the follow up. CONCLUSION:
      Considering our review and the current literature, it seems that complete
      excision followed by adjuvant radiotherapy of more than 50 Gy significatively
      reduces the risk of recurrence (p < 0.0001). Radiosurgery is indicated for
      recurrent tumors measuring less than 30 mm in their greatest diameter.

PMID- 9757313
TI  - [Primary central nervous system lymphomas. Diagnostic and prognostic effect of
      steroid-induced remission].
AB  - PURPOSE: Non-AIDS primary central nervous system lymphomas may respond totally or
      partially to corticosteroids. These corticoid-induced remissions seems to be very
      specific for this disease. They have been proposed as diagnostic test. The effect
      of these remissions on prognosis remains unknown. METHODS: A retrospective study
      was conducted. Corticosteroid sensibility, duration of survival, duration of
      disease free interval and type of treatment were compared between two groups of
      patients. The first one (group 1) included 44 patients in which exact diagnosis
      was made by stereotactic biopsy or surgery. The second group (group 2) included 5
      patients exhibiting typical neuroradiological aspects of primary lymphoma in whom
      corticosteroid therapy produced a total regression of the lesions. RESULTS: In
      group 1, 29.1% of the lymphomas exhibited cortico-sensitivity. Duration of free
      interval of disease accounted for 75% of the overall duration of survival. Age
      was the only significant factor predicting remission (p = 0.019). The sole factor
      influencing total duration of remission was the type of treatment (p = 0.03).
      Duration of remission was significantly shorter in group 2 versus group 1
      patients (p = 0.007). CONCLUSIONS: Duration of the first remission is of
      paramount importance on survival as well as the quality of first line therapy. In
      these conditions the absence of precise diagnosis due to corticoid-induced
      remissions could be dramatically deleterious.

PMID- 9757314
TI  - Ki-67 antigen expression as a prognostic factor in primary and recurrent
      astrocytomas.
AB  - BACKGROUND AND PURPOSE: Histological grading is widely used to evaluate the
      prognosis for patients with astrocytic tumors. Many complimentary methods have
      been introduced, such as proliferation markers in order to better assess the
      proliferative potential of these gliomas. METHODS: Archival, paraffin embedded
      specimens of recurrent astrocytic tumors of varying grades from 22 patients were
      examined using antibodies against Ki-67 (MIB-1). Labeling indices (LI) were
      analyzed at the first and second operations and compared with tumor grades, age
      of the patients and the time between the operations as well as the survival time.
      RESULTS: There was a progression of malignancy between the operations. Dividing
      Ki-67 labeling indices in < or = 10% vs. > 10% significantly separated parameters
      such as the time between the first operation and relapse as well as the
      cumulative proportion of survival. The proliferation fraction was an independent
      prognostic factor. CONCLUSION: Assessment of Ki-67 LI is highly recommended in
      addition to histology in evaluation of the malignancy potential of astrocytic
      tumors.

PMID- 9757315
TI  - [Seizure-linked hippocampal plasticity and protection against excitotoxicity:
      possible role of neuropeptide-y].
AB  - BACKGROUND AND PURPOSE: Changes occurring in neuropeptide-Y immunoreactivity
      after kainic acid injection in rats and their possible consequences on seizure
      brain damage were studied. METHODS: First, an intra-hippocampal kainic acid
      injection was performed (n = 7), inducing an ectopic and bilateral neuropeptide-Y
      immunoreactivity in mossy fibers. On the side of the injection, this neuropeptide
      Y staining was associated with dramatic neuronal loss whereas, in the
      contralateral hippocampus staining was observed without associated neuronal loss.
      The CA3 a-b pyramidal cell loss induced by an intra-ventricular kainic acid
      injection was then compared between a control group (n = 6) and a pre-conditioned
      group (n = 6) characterized by neuropeptide-Y staining in the mossy fibers
      obtained by a previous contralateral intra-hippocampal kainic acid injection as
      described. RESULTS: In the pre-conditioned group, the CA3 a-b pyramidal cell loss
      was significantly lower (m = 33.5%) than in the control group (m = 86.6%). The
      neuropeptide-Y inhibiting the pre-synaptic release of glutamate, glutamate
      related epileptic-brain damage could be reduced when neuropeptide-Y is expressed
      by granulated cells. IN CONCLUSION: Seizure-linked plasticity could induce a self
      protection phenomenon against excitotoxic lesions possibly partially mediated by
      de novo neuropeptide-Y mossy fiber expression.

PMID- 9757317
TI  - [Trauma-induced arterial aneurysm in childhood. Report of a case and review of
      the literature].
AB  - We report a case of calloso-marginal artery aneurysm in a 3 year old child,
      revealed 3 weeks after a craniocerebral trauma with frontal embarrure, by a
      sudden subarachnoidal hemorrhage syndrome with loss of consciousness and coma.
      The CT scan confirmed the subarachnoid hemorrhage in all the basal cisterns, with
      an interhemispheric subdural hematoma. The carotid angiography showed a right
      calloso-marginal aneurysm. The child has been operated (coagulation of the artery
      and excision of the false aneurysm. We studied the mechanism of pediatric post
      traumatic aneurysm, the histological and clinical presentation emphasizing the
      necessity of a complete neuroradiological exploration when new neurological
      symptoms develop after head trauma. Neurosurgical and/or endovascular
      neuroradiological treatment is mandatory.

PMID- 9757316
TI  - [Extracranial trigeminal schwannomas with middle temporal fossa development].
AB  - Schwannomas of trigeminal nerve account for 0.07% to 0.36% of all intra-cranial
      tumors. We report three observations about Jefferson's type D tumors, mainly
      extra-cranial with only small intra-cranial extension, concerning two men and one
      woman, who were respectively 36, 60 and 63 years old. Two of them presented with
      facial pain and hypoesthesia in the same territory. The third one developed a
      diplopia. In all cases, CT scanner analysis evidenced a large hypodense tumor
      extending in the infratemporal fossa. Temporal lobe and cavernous sinus were
      pushed aside by the intra-cranial extension. Tumors were hypo intense in T1
      weighted image with significant enhancement after gadolinium injection. One of
      the tumors was a cystic form and in that case, an hyper signal in T2-weighted
      image was detected in the middle of the lesion. A combined subtemporal and
      transmaxillary approach was performed in 2 cases. In the third case, the removal
      of the tumor was only performed by a transmaxillary approach. In this series,
      there was no surgical mortality. One patient presented a postoperative residual
      painful anesthesia. In conclusion, extra-cranial schwannomas with intra-cranial
      extension are specially rare lesions. The most common early symptoms are facial
      neuralgia, facial hypoesthesia or diplopia. Neuroradiologic investigations,
      including CT and MRI evidence the precise anatomic site of the lesions. With the
      help of these techniques, total surgical tumor removal is possible in the
      majority of cases.

PMID- 9757318
TI  - [Combination treatment for pilocytic astrocytoma: stereotaxic radiosurgery and
      endocavitary radiotherapy].
AB  - The treatment of a pilocytic astrocytoma located in a functional area can be
      performed using radiosurgery. We report a 7 year old male, right-handed, who
      presented with a pilocytic astrocytoma in the left parieto-occipital lobe. After
      a 7 year follow-up, the tumor became symptomatic (partial and generalized
      seizures). The CT scan and nuclear magnetic resonance imaging revealed an
      increased size of the mural tumor and the development of a cystic component.
      Multi-beam irradiation of the tumor (dose of 30 Gy at the center with 21 Gy on
      the isodose 70%) was performed with a LINAC for radiosurgery coupling a modified
      Saturne 18 MeV linear accelerator and a Talairach stereotactic frame. Following
      multi-beam irradiation, the increase in size of the cyst imposed further
      intracavitary radiation using Rhenium 186 (186Re) to deliver 400 Gy to the cyst
      wall. After a period of intense cerebral edema, resolutive with steroid
      treatment, we obtained progressive cyst disappearance and mural nodule
      retraction. A PET scan, performed 3 years after this treatment, revealed no
      metabolic activity in the persistent mural nodule. The patient remains totally
      asymptomatic.

PMID- 9757319
TI  - [Guide-lines for head injured patients management in adult age. Neurosurgical
      Society of France].

PMID- 9757320
TI  - [The development of neurosurgeons in France and accreditation].

PMID- 9757321
TI  - [Development of the corpus callosum (CC)].
AB  - Corpus callosum embryology can be divided into three parts: during
      "commissuration", a cellular mass develops between the two telencephalic
      vesicles. The primitive lamina terminalis corresponds to the closing point of the
      anterior neuropore. Its dorsal part grows and forms the lamina reunions (6-8
      intra uterine weeks, IUW). From ventral to dorsal, this lamina reunions gives
      rise to the area praecommissuralis (origin of the anterior commissure), to the
      primordium hippocampi (10 I.U.W., fornix), and to the massa commissuralis (10
      S.I.U., corpus callosum). Fibers arising from the developing hemispheres run
      through this primitive corpus callosum. The growth of the corpus callosum follows
      the expansion of the hemispheres, in a rostro-caudal and then dorso-ventral
      circular movement. The last part of the corpus callosum to form is the rostrum.
      Maturation occurs postnatally, and corresponds to axonal elimination, and
      myelination, progressively changing the callosal connection pattern of the
      newborn and infant into the adult pattern.

PMID- 9757322
TI  - [Morphologic anatomy of the corpus callosum].
AB  - The corpus callosum is a neopallial commissure. In inferior vertebrates, the
      pallial commissures are essentially represented by the anterior commissure. The
      corpus callosum appears in mammals only. Eutherians alone have a corpus callosum,
      the other mammals have an anterior commissure and hipocampal commissure. In
      humans, the different portions of the corps callosum are described on a median
      sagittal slice: rostrum, genu, body, isthmus, splenium. Klingler method allows to
      dissect fibers of each of these portions and their relationship with the corona
      radiata and optic radiations. These latter are separated from the ventricular
      ependyme by callosal radiations. Finally, each part of the corpus callosum
      participates in lateral ventricle wall formation.

PMID- 9757324
TI  - [Anatomic MRI study of commissural agenesis and dysplasia of the Telencephalon
      (Agenesis of the corpus callosum and related anomalies). Clinical correlations
      and morphogenetic interpretation].
AB  - A series of 78 patients presenting with agenesis of the cerebral commissures and
      properly investigated with MR imaging, was reviewed and analyzed morphologically.
      Results were compared with descriptive data from the literature, and with the
      developmental models proposed. From this, a model of a-commissural brain is
      described: the lamina terminalis would be homologous to a telencephalic anterior
      medullary velum of which the commissure would be the anterior commissure, and the
      lamina of white matter described as the Probst's and the fornical bundles, would
      be homologous to a posterior medullary velum having become a medial medullary
      velum due to the division of the prosecephalon into two cerebral hemispheres, and
      of which the commissure would be the (posterior) calloso-hippocampal commissure.
      Also, the comparison with the model establishes that in the actual malformations,
      defects of the cingulum and of at least some of the intralobaroccipital
      association bundles are observed beside the commissural defect. Such a model
      would reclassify these disorders, distinguishing the "simple" commissural
      defects, complete or segmental, global or dissociated, without or with a
      ventricular expansion, from more complex forms with multicystic defects, adding
      major dysplastic lesions of the dura mater, leptomeninges and parenchyma, to the
      commissural defects. Paradoxically, the latter group seems to be clinically less
      severe than the "simple agenesis" group, of which prognosis (including the
      neurologic and intellectual disorders as well as the associated pathologies) is
      generally very poor; this should be seriously considered since the antenatal
      diagnosis of these malformations is made routinely with ultrasonography and MRI.

PMID- 9757323
TI  - [Arterial and venous vascularization of the corpus callosum].
AB  - Blood supply of the corpus callosum is assured by two arterial systems, the
      carotid system mainly and the vertebrobasilar system accessorily. The carotid
      system intervenes via the pericallosal artery, portion of the anterior cerebral
      artery distal to the anterior communicating artery. This pericallosal artery can
      be bihemispheric in 4 to 12% of the cases or azygos in 0.26% of cases. In 20 to
      80% of cases, the median callosal artery arises from the communicating artery.
      The vertebrobasilar system intervenes in splenium vascularization by its terminal
      branches. These two carotid and vertebrobasilar systems give rise to perforating
      arteries that assure intrinsic vascularization of the corpus callosum creating a
      system of regular vascular stitches around the fibers of the corpus callosum. The
      venous drainage of the corpus callosum is essentially via callosal veins and
      callosocingulate veins towards the deep venous system of the brain.

PMID- 9757325
TI  - [Histogenesis of the corpus callosum].
AB  - The corpus callosum results from neocortical commissural axon fasciculation. Its
      development reflects the interhemispheric circuitry and then follows the
      successive steps of synaptogenesis. The first stage consists of callosal neuron
      differentiation, which allows the extention of the future callosal axon; this is
      an early event that occurs while neuronal migration to the cortical plate is
      still ongoing. Callosal axon guidance towards its specific target is the second
      step which includes reaching and crossing the midline and further target
      recognition with formation of initial synapses. This period extends from 12 to 22
      post-conceptional weeks and corresponds to the following histological features:
      i) progressive invasion by callosal growth cones of the dorsal part of lamina
      reuniens through a preformed glial pathway; ii) appearence of the three parts of
      corpus callosum, namely truncus, rostrum and lastly the splenium. Both these
      stages are genetically controlled either directly by developmental gene
      expression (neurogenesis genes) or indirectly by the establishment of cue maps
      (spatial expression of extra-cellular matrix proteins). The third step is that of
      synapse remodeling by synaptic activity, giving rise to axonal elimination,
      macroscopically revealed by a transitory thinning of corpus callosum. This
      perinatal event contributes to the corpus callosum acquiring a mature topography.
      Finally, analysis of corpus callosum ontogenesis appears as a striking model of
      synaptogenesis study and provides physiopathological assumptions for a
      understanding of the corpus callosum agenesis.

PMID- 9757326
TI  - [Agenesis of the corpus callosum. Neuropathologic study and physiopathologic
      hypotheses].
AB  - The neuropathological study of corpus callosum agenesis requires a two-phase
      approach: first it should analyze the putative causal factors, i.e. absence of
      callosal neurons, commissuration inability or synapse remodelling defect;
      secondly it has to detect any morphogenetic effects stemming from the absence of
      commissure such as nonregression of archicortical structures, ventricular
      enlargement or possible invasion of the remaining telencephaplic commissure by
      callosal neurons. Absence of callosal neurons due to abnormal corticogenesis
      gives rise to corpus callosum agenesis without callosal axon, that is without
      Probst's bundles. Conversely, corpus callosum agenesis occurring secondary to a
      commissuration default is associated with the presence of callosal axons which
      travel along the midline instead of crossing, that leads to the formation of
      Probst's bundles. This inability to cross the midline could be secondary to an
      obstacle, such as lipoma or as interhemispheric cysts, or primitive due to axonal
      guidance disturbance. In the latter situation, the commissural defect could
      affect the other cerebral commissures i.e. anterior or hippocampal commissures,
      or could become integrated into a more diffuse midline pathology involving both
      cerebral and extracerebral structures. Finally, it could be assumed that a
      synapse remodelling defect could lead to atrophy or hypertrophy of the
      commissure, that occurs in the absence of white matter pathology.

PMID- 9757327
TI  - [Prenatal diagnosis of anomalies of the corpus callosum with ultrasound: the
      echographist's point of view].
AB  - Ultrasonography can identify agenesis of the corpus callosum (excluding
      holoprosencephaly which an be detected earlier on) in the second trimester of
      pregnancy (18-20 weeks gestation). Diagnosis of corpus callosum agenesis is
      difficult but is important as a risk factor for neurological or genetic
      malformations. The characteristic signs suggestive of corpus callosum agenesis
      are: moderate distension of the occipital ventricle and the ventricular
      communications; absence of the spectrum giving rise to an upward displacement of
      the third ventricle shown in the anterior coronal section (especially in
      transvaginal ultrasonography); radial position of the fissures on the internal
      side of the cerebral hemisphere seen on the sagittal section; the absence in
      color coded Doppler of the pericallosal artery normally characterised by a
      semicircular vessel observable on the median sagittal section. At present, color
      coded Doppler should give the diagnosis of corpus callosum agenesis. MRI can
      provide further information especially in case of late detection around 28-30
      weeks gestation as is most frequently the case. The development of 3D echographic
      imaging should allow an even more sophisticated approach to this diagnosis giving
      even more precise prognosis. Isolated corpus callosum agenesis is compatible with
      normal intellectual development an raises an important problem with regard to
      pregnancy continuation and infant development. Each individual case should be
      discussed during the pluridisciplinary prenatal diagnostic discussion.

PMID- 9757328
TI  - [Obstetrical management of agenesis of the corpus callosum].
AB  - We present a multicenter analysis of 24 cases of prenatal diagnosis of corpus
      callosum agenesis and review the literature concerning prognosis factors for
      continuing or interrupting pregnancy.

PMID- 9757329
TI  - [Prognosis of isolated agenesis of the corpus callosum].
AB  - We report preliminary results of a three year follow-up of ten children affected
      with apparently isolated corpus callosum agenesis (prenatal diagnosis). This
      population was collected from a multicenter prospective study: annual survey
      included physical examination, developmental outcome and psychometric evaluation.
      Febril convulsions appeared to be more frequent than in the general population;
      developmental outcome was normal at the last evaluation. Follow-up has to be
      performed up to 10 years to determine more accurately prognosis of isolated
      corpus callosum agenesis.

PMID- 9757330
TI  - [Genetics of agenesis of the corpus callosum].
AB  - Agenesis of corpus callosum (ACC) is one of the most common brain malformations
      observed in humans. It is a heterogeneous malformation, with many etiologies.
      Isolated ACC is usually sporadic but familial cases have been reported. ACC can
      complicate numerous polymalformative, either monogenic or chromosomal syndromes.
      In some of them, for example Aicardi syndrome, Anderman syndrome or acrocallosal
      syndrome, ACC is a mandatory manifestation. Further identification of the
      molecular bases of these syndromes will be helpful in understanding the causal
      heterogeneity of this malformation.

PMID- 9757331
TI  - [Corpus callosum disconnection syndromes and functional organization or the
      corpus callosum in adults].
AB  - Knowledge concerning the role of the corpus callosum derives from the study of
      patients with lesions of spontaneous or surgical origin. Three major aspects are
      defined: interhemispheric elementary transfer of symmetrically organized
      messages, complex transfer of asymmetrically organized information,
      interhemispheric transfer and complex behaviors. Symptoms are both complex and
      rather limited; they can be missed if they are not specifically searched for.

PMID- 9757332
TI  - [Corpus callosum syndrome in children].
AB  - The survey of callosotomized children is a difficult because they often present a
      severe epilepsy with mental retardation. The younger the child, the better he
      recovers. The child can be considered as a physiological split-brain. If one
      compares commissurotomized children with those presenting an agenesis of the
      corpus callosum, the later ones have, to a certain extent, an interhemispherical
      transfer which suggests supportive ipsilateral or sub-cortical connections.

PMID- 9757333
TI  - [Interhemispheric transfer and agenesis of the corpus callosum. Capacities and
      limitations of the anterior commissure].
AB  - In case of agenesis of the corpus callosum, four hypotheses may be proposed to
      explain how compensation of the interhemispheric transfer might take place. These
      hypotheses include the use of cross-cueing behavioral strategies, the bilateral
      representation of speech-functions, the increased use of ipsilateral sensory
      motor pathways, and the use of noncallosal commissures. Among all these
      compensatory mechanisms, the last one, namely the increased use of the anterior
      commissure, is the most significant. It can easily explain that acallosal
      patients with an anterior commissure (which can be increased in size), have
      better results in interhemispheric transfer tests, and in neuropsychologic tests,
      than patients having no anterior commissure. However, the anterior commissure
      alone, even increased in size, cannot normalize all the interhemispheric transfer
      tests, because of the big difference between the field of origin of the callosal
      fibers, and the field of origin of the anterior commissure fibers.

PMID- 9757334
TI  - [Acquired lesions of the corpus callosum].
AB  - Acquired lesions of the corpus callosum may be related to tumoral, vascular,
      traumatic or degenerative disorders and, one must not forget, can result from
      surgical access. Currently, the quality of neuroimaging enables a validation or
      precision of anatomoclinical, neuropsychological and neurophysiological
      correlations established from experimental and/or autopsy data. However the
      "specific" signs of acquired lesions of the corpus callosum are often quite
      complex and may be readily overlooked or masked within a heterogeneous clinical
      presentation due to more or less important associated lesions of neighboring
      structures. Therapeutic management (tumors, arteriovenous malformations,
      cavernomas) depend on the nature and the extent of the lesion more than the
      functional nature of this inter-hemispheric commissure with an exceptional
      functional plasticity, particularly when the lesion is limited.

PMID- 9757335
TI  - [Lipoma of the corpus callosum].
AB  - In the central nervous system, 40% of all lipomas develop in the anterior third
      of the corpus callosum. In 48% of the cases, there is partial agenesia of the
      corpus callosum. In 50% of the cases, there is no clinical expression. In cases
      with epilepsy, surgery has no effect on seizures and is difficult due to the
      arterial relations.

PMID- 9757336
TI  - [Surgery and epilepsy].
AB  - Corpus callosotmy was introduced in 1940 as a palliative treatment for
      generalized epilepsies. The improvement of the surgical technique, and the
      simplification of the initial "total commissurotomy" made that procedure proposed
      in order to decrease the frequency and the severity of the seizures occurring in
      the secondary geralzed epilepsies. However the indication criteria remain
      unclear, due to the difficulty for analysing the results and the feterogenity of
      the series. A careful selection requiring a comprehensive epilepsy team remains
      mandatory despite the relative simplicity of the procedure.

PMID- 9757337
TI  - [Surgical approaches to the corpus callosum].
AB  - There are no dedicated approaches to the corps callosum itself. The different
      approaches, subcallosal, supracallosal and posterior to the splenium are usually
      used to reach neighboring structures such as third ventricle or pericallosal
      arteries. MRI is the best guideline to reach a specific position in the corps
      callosum and must imperatively contribute to the choice of the type of approach.
      During the procedure, it is necessary to take great care to protect the vessels,
      arteries and veins especially, to avoid ischemic damage which is the main
      complication of these approaches.

PMID- 9757338
TI  - [Tethered cord syndrome in adults].
AB  - A series of 25 adult patients surgically treated for a tethred cord syndrome is
      reported. Preoperatively 19 patients presented with a sensorimotor deficit in
      their lower limbs, 17 with sphincter disturbances, 12 with pain and/or
      neuroorthopedic symptoms and 9 with cutaneous lumbar anomalies. At surgery, an
      isolated anomaly (lipoma, anomalous or adherent filum terminale) was disclosed in
      18 patients. In the remaining 7, a more complex form of dysraphism was disclosed.
      Follow-up ranges from 3 months to 20 years (mean: 6.5 years). Ten patients
      improved, 6 were stabilized and 9 showed continuous worsening. The best results
      were obtained in patients in whom the cord tethering resulted from an anomalous
      filum terminale. Results were significantly worse in patients suffering long
      standing symptomatology and showing either radiologically or surgically mixed
      mechanisms of cord tethering. Early surgical correction should be idealy
      undertaken in patients suffering from minor neurological deficits and in whom
      magnetic resonance imaging illustrates a low conus medullaris attached by a short
      thickened filum terminale.

PMID- 9757340
TI  - [Presurgical evaluation of cerebral tumors with functional MRI].
AB  - PURPOSE: To evaluate the capabilities and the limitations of motor functional
      magnetic resonance imaging (FMRI) in the presurgical planning of the cerebral
      tumors located in or near the motor homunculus and to correlate each type of
      activation with the histologic characteristics of each tumor. MATERIALS AND
      METHODS: FMRI was performed in 17 patients (14 adults and 3 children), without
      motor deficit, presenting with various intra cerebral tumors. Three FMRI
      activation paradigms were used, controlateral to the lesion: ballistic opposition
      of the fingers, flexion-extension of the foot and click of the tongue. Four
      patients, without motor deficit, with cerebral tumors far from the motor
      homunculus were used as control group to look for non specific activations. In
      all cases, the histopathology of the tumor was known accurately. RESULTS: In 11
      patients with infiltrating tumors, the activated areas were clearly displaced.
      They were often intratumoral and scattered in correlation with the degree of
      infiltration. Two patients with non infiltrating tumors (meningioma) showed
      extratumoral shift of the activated areas. Four patients presenting cerebral
      tumors far from the homunculus motor did not show intratumoral activation. The
      supplementary motor area and the ipsilateral primary motor cortex were also
      sometimes activated during the motor tasks. The task of the tongue was often
      artifacted, probably because of the head motion. CONCLUSIONS: These preliminary
      results suggest that the histopathologic characteristics of a tumor and
      especially its microscopic structure plays a role, with others factors, on the
      motor functional area organization. In a small number of cases, the data obtained
      from the FMRI could be used intraoperatively, with a neuronavigation system.

PMID- 9757339
TI  - [Therapeutic strategy for cerebral arteriovenous malformations. Proposal for
      classification of individual hemorrhagic risk].
AB  - BACKGROUND AND PURPOSE: Therapeutic strategy for the cerebral arteriovenous
      malformations (cAVM) is mainly based on the assessment of hemorrhage risk. This
      risk is estimated between 2 and 4% according to various series. However, this is
      a collective risk projected upon a given population. To improve therapeutic
      strategy for cAVM, we propose a grading of the individual hemorrhage risk based
      on 5 angiographic parameters: 4 are increasing risk factors and one is a
      favorable index. METHOD: This grading system has been achieved by univariate then
      multivariate analysis by logistic regression from angiographic data of 250
      consecutive patients with cAVM. Thirty angiographic parameters were studied.
      RESULTS: Grade I has no risk factors and has two subgrades: Ia with venous
      recruitment (which is the lonely favorable parameter), Ib without venous
      recruitment. Grade II is the presence of venous stenosis or venous reflux. Grade
      III is the presence of exclusive deep venous drainage. Grade IV is the presence
      of intra or juxta-nidal aneurysm. There were 13% of hemorrhage in grade Ia, 38%
      in grade Ib, 48% in grade II, 90% in grades III and IV. CONCLUSIONS: This model
      can be helpful for the treatment decision making and also contributes to a better
      understanding of the natural history of cAVM. It must be further confirmed by a
      prospective study.

PMID- 9757341
TI  - [Use of the CCD (Sofamor-Danek) rod plates for instabilities of the craniospinal
      junction].
AB  - We report our experience with the CCD material (Sofamor-Danek) for the treatment
      of cranio-cervical instability. In this method, rod-plates are fixed to the
      occipital bone and to the cervical spine with hooks. This technique is mainly
      indicated for the treatment of patients with severe osteoporosis or with
      significant thinness of the occipital bone. Four cases are presented. Three of
      them suffered from a inflammatory rheumatism. The fourth patient had been
      previously treated by an occipito-cervical fixation with a Roy-Camille plate for
      a C2 metastasis and presented a failure of the occipital screws fixation. In all
      cases, no post operative complications were observed and all patients had a
      significant improvement of their cervicalgia. We confirm the interest and the
      fiability of the CCD method which has simplified the procedure and is specially
      suitable for the treatment of all types of cranio-cervical instability, even in
      the most adverse conditions.

PMID- 9757342
TI  - [Subarachnoid hemorrhage syndrome and its aneurysmal etiology. From Morgagni to
      Moniz, Dott and Dandy. A historical overview].
AB  - Although obvious today, the concept of subarachnoid hemorrhage due to ruptured
      intracranial aneurysms emerged slowly in medical knowledge with the clinical and
      pathological observations of many perspicacious authors beginning with Morgagni
      in the middle of the eighteenth century. This body of clinical material made it
      possible for Symonds in 1924 to affirm this concept on clinical and pathological
      grounds just a few years before Egas Moniz performed the first cerebral
      angiograms and such pioneers as Norman Dott and Walter Dandy the first direct
      attacks on cerebral aneurysms.

PMID- 9757343
TI  - [The retro-auricular, transmastoid, infralabyrinth approach. A simple route for
      excision of tumors of the jugular foramen].
AB  - BACKGROUND: The jugular foramen is a complex area of the skull base. Its
      contents, the anatomical relationships in the region, and its location at the
      skull base, are responsible for problematic surgical approaches. The classical
      infratemporal surgical routes remain complex and difficult to perform. The
      lateral approach through a mastoidectomy is almost always associated with an
      anterior transposition of the facial nerve although that transposition is usually
      unnecessary. METHODS: Progressive drilling along the sinusojugular axis, inferior
      to the labyrinth and medial to the third portion of the facial nerve, combined
      with a simple neck dissection, allows the surgeon to nicely expose the jugular
      foramen. The surgical procedure is described, following a brief anatomical
      reminder of the essential relationships in the area. A clinical observation is
      used to illustrate the purpose. RESULTS: Most schwannomas of lower cranial nerves
      and small glomus jugulare tumors should be resected using this approach, which is
      a simplified lateral approach, without post operative facial palsy or cophosis.
      CONCLUSIONS: The infralabyrinthine approach is a simple way to expose the jugular
      foramen region compared with infratemporal complex and time-consuming approaches.

PMID- 9757344
TI  - [A peculiar mechanism of hydrocephalus: the "water-hammering" effect].
AB  - BACKGROUND AND PURPOSE: Aneurysms of the basilar artery can cause hydrocephalus
      due to compression of the third ventricle or the sylvian aqueduct. The
      observation of a particular case led to discuss another possible mechanism of
      hydrocephalus. CLINICAL PRESENTATION AND RADIOLOGICAL STUDIES: An aneurysm of the
      basilar artery was revealed by an ischemic stroke in a 65-year-old man.
      Hydrocephalus developed during the following months. The MRI studies showed that
      it could not be explained merely by a permanent compression. However, the patient
      improved clearly after a ventriculo-peritoneal derivation. CONCLUSION: The
      hydrocephalus could be explained by a "water-hammering" effect due to the
      pulsating blood in the ectatic vessel, which created a cerebrospinal fluid
      outflow impairment through the third ventricle.

PMID- 9757345
TI  - [A free meningioma of the cauda equina].
AB  - We report an unusual case of a cauda equina meningioma occurring in a young girl.
      This tumor was neurinoma-like. No meningeal attachment was identified in the
      neuroradiological study and during its microsurgical removal.

PMID- 9757346
TI  - [Chronic subdural hematoma in utero. Case report with literature review].
AB  - We present a case of chronic subdural hematoma diagnosed in utero by
      ultrasonography, and MRI at 31 weeks gestation. No cause of usual intracranial
      hemorrhage was found. There was no trauma. The child was operated after induced
      vaginal delivery at 37 weeks gestation, with good results and normal
      neuropsychological development after one year. We discuss the symptomatology and
      the therapeutic attitude in such cases.

PMID- 9757347
TI  - [Isolated intramedullary cysticercosis. Case report].
AB  - BACKGROUND AND PURPOSE: Cysticercosis is the most common parasitic disease
      affecting the central nervous system. Although it is still very rare in Europe,
      the frequency will increase due to the influx of immigrants from the endemic
      areas and increasing trips in these countries. Spinal intramedullary
      cysticercosis is an uncommon manifestation of neurocysticercosis. CLINICAL
      PRESENTATION: We report a case of pure intramedullary cysticercosis in a young
      white French girl, presenting as a progressive paraplegia with a cystic lesion in
      T4 on MRI. The diagnosis was made only after surgery by pathological examination.
      CONCLUSIONS: A preoperative diagnosis of spinal intramedullary cysticercosis must
      be suspected not only in an endemic area in the presence of multiple soft tissue
      calcifications and segmental lesions revealed by myelography or MRI studies, but
      also for all cystic lesion of central nervous system even in no endemic area.
      Surgery is the unique treatment which can be used for spinal intramedullary
      cysticercosis and with the use of the microsurgical techniques for medullar
      surgery the outcome is not as dismal as reported earlier.

PMID- 9757348
TI  - [Guidelines concerning severe cranial trauma. French Society of Neurosurgery].

PMID- 9757349
TI  - [Suicide of children and adolescents].
AB  - The retrospective analysis of the Bonn autopsy material from 1992 to 1996
      revealed 11 suicides of children and adolescents, 8 girls and 3 boys. The ages
      ranged from 10 to 19 years. The suicides occurred preferentially outdoors in the
      warm months of summer, on Monday and in the middle of the week, in the afternoon
      and early evening hours. Independent from sex, the children unexceptionally
      applied hard suicide methods like hanging or jump from the height. As for the
      psychological background, current conflicts within the family or at school on the
      background of chronically disturbed family structures were encountered as
      prevailing factors.

PMID- 9757350
TI  - [Fatal child abuse in Japan and Germany. Comparative retrospective study].
AB  - In this study a record for comparative international epidemiological studies on
      autopsy cases of child abuse is introduced. The form was proved in a
      retrospective comparative survey of cases of fatal child abuse at the Department
      of Legal Medicine in Kanazawa (Japan) and Institute of Legal Medicine of Lubeck
      (Germany). A total of 33 cases were included. The following data were evaluated:
      age and gender of victims and assailants, relationship between victims and
      assailants, causes and methods of abuse, chief autopsy findings, and causes of
      death. The results were leading into two directions between Kanazawa and Lubeck:
      (1) In the years of 1981-1996 in Kanazawa 23 cases of fatal child abuse were
      autopsied while during the same period in Lubeck only 10 cases were registered.
      (2) While sexual abuse was not registered in Kanazawa, it was recorded twice in
      Lubeck.

PMID- 9757351
TI  - [Simulated suicide by hanging after homicidal strangulation].
AB  - Homicides by hanging and the simulation of suicide by hanging a victim previously
      killed or made unable to resist by other means are regarded as extremely rare
      events, although especially in German forensic literature cases of this kind were
      repeatedly reported. The paper adds another example to the number of observations
      published so far: A 23-year-old student strangled his 58-year-old father with an
      electric cable until he ceased to show any signs of life. Then he hanged the
      victim at the handrail of the staircase with a running noose. From the forensic
      point of view the following clues pointed to homicide: presence of massive signs
      of facial congestion in spite of the "typical" situation of hanging, horizontal
      ligature mark in addition to the noose mark, skin injuries at the head and the
      upper extremities, traces of blood near the place where the body was found. The
      case history presented emphasizes again that for differential diagnosis the
      possibility of a dissimulated homicide has to be considered in all cases where a
      body is found suspended.

PMID- 9757352
TI  - [A case of suicidal chloroform poisoning].
AB  - A 33-year-old man who had suffered from phobia and depressions was found dead in
      his kitchen. He was entirely covered by plastic waste disposal bags stuck
      together. The corpse was lying flat on his stomach with his face on a towel
      soaked with chloroform. Within the plastic cover, on either side of the body's
      head, there was located a can half way filled with chloroform. Autopsy revealed
      cauterized lips and mucous membranes of the mouth. The morphological findings of
      the inner organs were unspecific. For toxicological analyses, air samples from
      the pleural cavities of the corpse were taken by way of charcoal tubes and a
      microprocessor aided pump. The solvents adsorbed on the charcoal were desorbed
      with benzyl alcohol and analyzed by gas chromatography according to standard
      procedures. The quantification of the chloroform levels of the body fluids and
      the tissue samples of the corpse was performed by extraction with pentane
      followed by addition of trichloroethylene as internal standard and consecutive
      gas chromatographic analysis. The results of the toxicological analyses confirmed
      the diagnosis of a fatal chloroform intoxication.

PMID- 9757353
TI  - [Exhumation and no end. A comparative analysis].
AB  - If the order to carry out an autopsy has been neglected, exhumation is the only
      possibility to obtain findings which allow conclusions on the manner of death,
      cause of death and chain of events. The quality of findings will however be
      influenced by advanced states of putrifaction. In spite of identical legislature
      the number of exhumations carried out at the institutes of legal medicine in
      Munchen and Munster differs considerably, as demonstrated by a comparison of the
      data from the years 1993-1996. As previously described by other authors, there is
      a reciprocal correlation between the number of autopsies and the exhumation rate.
      The frequency of autopsies which are ordered can be explained by the varying
      application of the statutory framework by the investigation procedure. In some
      cases where an exhumation has been carried out, it was difficult to comprehend
      why an autopsy was not originally ordered.

PMID- 9757354
TI  - [Expert assessment of coital injuries from the forensic medicine viewpoint].
AB  - A 38-year-old woman was transmitted to hospital with profuse vaginal bleeding.
      The origin of the vaginal injuries (resulting from "normal" sexual intercourse
      vs. use of instruments for manipulation in the vagina) was obscure. The wound
      pattern is presented and the literature on the subject is reviewed with special
      reference to predisposing factors and genesis of coital injuries. Concerning the
      wound pattern, reflecting a blunt trauma, a manipulation with a (so far unknown)
      instrument, but also with finger or hand could not be proved with the required
      certainty. In the presented case the origin of the vaginal injuries from "normal"
      sexual intercourse as described by the accused man could not be excluded.

PMID- 9757355
TI  - [Suicide by a borderline patient at the end of fatal self-destructive behavior].
AB  - The presence of a borderline personality disorder must also be considered in
      forensic medicine appraisements, beside the various motivations for a self
      injurious behaviour and apart from other psychiatric illnesses. This personality
      disorder is frequently characterized by cuts and scratches made by the patients
      using sharp objects to inflict themselves when in situations causing great
      psychological distress. A case of a young female student is presented who
      exhibited a clear auto-destructive behaviour. Due to a tragic psychodynamic
      development, she committed suicide by means of carbamazepine intoxikation. In
      addition to the impressive morphological and traumatological injury pattern, the
      psychiatric case history of the female patient also showed that she had suffered
      from a typical borderline personality disorder.

PMID- 9757356
TI  - Epidemiology, risk factors, intervention, and prevention of adolescent suicide.
AB  - Increasing rates of adolescent suicide are a significant health concern and the
      third leading cause of death for this age group. Recent research into
      psychiatric, gender-related, family, cultural and neurobiologic risk factors is
      reviewed. The effects of suicide exposure and media influences are also examined.
      Although many risk factors have been identified, the application of this
      knowledge to clinical practice requires further study. The limited number of
      studies on prevention and intervention strategies are discussed. High rates of
      nonadherence to follow-up remain problematic. More research is needed to develop
      appropriate treatments, prevention programs and outcome measures.

PMID- 9757357
TI  - Recent patterns of use and associated risks of illicit drug use in adolescents.
AB  - Addressing adolescent substance abuse presents a tremendous challenge to the
      practicing clinician. Despite ongoing educational and preventive services, and
      despite increasing governmental interdiction, substance use by adolescents
      continues to be a major national problem. Although present rates of use are lower
      than the peak rates in the late 1970s, drug use among adolescents nearly doubled
      in the early 1990s and is a significant cause of morbidity and mortality.
      Patterns of use continue to evolve. Newer drugs make their way to the streets,
      and older drugs are rediscovered. Behavioral and environmental factors increase
      the risk for adolescent substance abuse. Identification of use patterns and
      familiarity with comorbid behaviors and social risks may help the clinician
      identify the adolescent at risk.

PMID- 9757358
TI  - Sports-related head injuries.
AB  - Head injuries in sports cause serious long-term problems. Appropriate acute and
      subacute management of both catastrophic and mild injuries can prevent secondary,
      potentially disabling or fatal injury. By understanding the mechanism of injury,
      classification, and epidemiology of sports-related head injury, pediatricians can
      appropriately care for their athletic patients. The symptoms of a mild head
      injury may be transient, but the cumulative effect may have permanent long-term
      sequelae. Continued clinical, epidemiologic, and basic science research is needed
      to help prevent head injuries and their sequelae in the future.

PMID- 9757359
TI  - Adolescents and violent crime.
AB  - Violent crime is a key social and public issue that significantly contributes to
      the morbidity and mortality of adolescents and places a significant economic
      burden on society. Overall, juveniles (legally described as adolescents under 18)
      are responsible for only 19% of all violent crime committed in the United States.
      However, the peak age incidence for violent offenders is 18, well within the
      spectrum of the adolescent age grouping. Over the past 10 years, arrests for
      juvenile crime have increased by 67%, leading some experts to worry that, given
      the expected increase in the size of the juvenile population by the year 2010,
      the number of arrests for juvenile crime will double. Fortunately, there has been
      a decline in the rates of juvenile violent crime over the past 2 years. This
      article reviews statistical trends, contributing factors and innovative
      approaches to prevention and intervention.

PMID- 9757360
TI  - Clinical disturbances of attachment in infancy and early childhood.
AB  - The development of the attachment behavioral system in infancy has been the focus
      of a wide range of research in the past 30 years. The clinical significance of
      disturbances in this area of development is currently a major focus for this
      research. Research on patterns of attachment in infancy has informed
      understanding of the development of psychopathology in later childhood; insecure
      disorganized attachment is recognized as an important risk factor in this regard.
      The clinical features of reactive attachment disorder in early childhood are also
      becoming more clear. Finally, knowledge about the intersection between attachment
      and various risk conditions is growing and should inform clinical judgement about
      infants and young children requiring intervention. Primary care physicians can
      use these findings to identify children in need of intervention.

PMID- 9757361
TI  - Childhood eating disorders.
AB  - This paper reviews the recent research literature on childhood eating disorders
      from a developmental perspective. Although there have been some recent advances
      in research, much work remains to be done, especially studies specific to child
      and adolescent eating disorders, as well as definitive follow-up studies. Few
      data are available on the normal development of eating behavior, or resilience
      and risk factors for eating pathology. The best-studied areas include
      epidemiological studies, short-term treatment for bulimia nervosa, and outcome in
      anorexia nervosa.

PMID- 9757362
TI  - Update on acne.
AB  - Acne is a common condition seen routinely by both primary care physicians and
      dermatologists. Most patients have no underlying pathology and respond to
      traditional treatment; others, however, require more individualized evaluation
      and aggressive therapy. New information regarding the pathogenesis and treatment
      of acne is now available. This update discusses the proper evaluation of early
      childhood acne, the emergence of Propionibacterium acnes resistance, and the rare
      but serious side effects occasionally seen with minocycline. Advances in the
      topical treatment of acne, the use of oral contraceptives in acne, and the use
      and efficacy of isotretinoin are also addressed.

PMID- 9757363
TI  - Atopic dermatitis.
AB  - Atopic dermatitis is the most common skin disease of childhood, and its
      prevalence has steadily increased over the last three decades. A chronic,
      relapsing condition, atopic dermatitis has a significant impact on affected
      children, their families, and the community at large. Although the fundamental
      pathogenesis has remained elusive, intensive research has greatly contributed to
      our understanding of this disease. As the specific immunobiologic pathways become
      deciphered, we have seen the propagation of several new therapeutic options that
      rationally attack specific underlying immune system abnormalities. This article
      highlights the specific contributions made to the literature over the past year,
      with particular attention to the immunopathogenesis of atopic dermatitis, as well
      as some new targeted therapies currently and soon to be available.

PMID- 9757364
TI  - Anogenital papillomavirus infections in children.
AB  - Over the years, our impression of human papillomavirus has changed. Once thought
      of as the cause of relatively insignificant skin lesions, its significant role in
      malignancy of epithelia and mucosa throughout the body is beginning to be
      understood. Also changing, although not as rapidly as we would like is our
      understanding of how human papillomavirus infects the body, the concept of
      latency, our responses to infection, and how to modify or boost those responses
      so as to overcome infection. Research into the specifics of how our immune
      systems react, or why they do not, should give us better insight into how and why
      treatment therapies work and how to optimize them. Further work into vaccines may
      provide the means to eradicate the virus from infected persons, as well as to
      prevent the initial infections.

PMID- 9757365
TI  - Moles and melanoma.
AB  - The melanoma epidemic in adults is well documented, and there is now evidence
      that the incidence of malignant melanoma in teenagers is increasing. Risk factors
      for melanoma are recognizable in children and include congenital nevi, numerous
      common nevi, and atypical nevi. Large congenital nevi overlying the head or spine
      also carry risk for central nervous system involvement, which, if symptomatic,
      carries a grave prognosis. Laser therapy has recently been advocated for small
      congenital nevi but often yields only temporary improvement. Adjuvant therapy
      with interferon alfa-2b holds promise for patients with metastatic melanoma.
      Melanoma risk is also linked to sun sensitivity and childhood exposures, and
      sunscreen use has been promoted for prevention of skin cancer. Because many
      sunscreens offer protection from ultraviolet (UV) B but not UVA, spectra that may
      be involved in melanoma induction, pediatricians should counsel their families to
      practice a full program of sun protection that includes sun avoidance and
      protective clothing and eyeware in addition to sunscreens.

PMID- 9757366
TI  - Laser therapy and dermatologic surgery.
AB  - Numerous advances in surgery and laser therapy applicable to pediatric
      dermatologic practice have been made. The use of EMLA (eutectic mixture of local
      anesthetics; Astra USA, Westborough, MA) cream (lidocaine and prilocaine) is
      invaluable for office dermatologic procedures in children. Despite high patient
      tolerance, rare adverse events have been described. Newer topical anesthetics
      with faster onset and greater efficacy are discussed, with special emphasis on
      their application to the pediatric dermatology patient. Appropriately
      administered, these newer agents may make certain procedures in children painless
      or minimally uncomfortable. Newer, improved tissue adhesives are under
      development and may replace and surpass traditional surface suturing. Limitations
      to the use of the pulsed dye laser for vascular lesions in children are
      discussed.

PMID- 9757367
TI  - Endocrine and metabolism.

PMID- 9757368
TI  - Growth hormone therapy for non-growth hormone-deficient children with short
      stature.
AB  - A summary of the majority of the available uncontrolled studies of 322 children
      with idiopathic short stature treated with growth hormone showed that the final
      height attainment over predicted adult height was only +2.85 cm (+0.49 SD score).
      Furthermore, a summary of seven studies reported that the spontaneous outcome in
      children with untreated idiopathic short stature was more than +1 SD score in
      final height compared to height at presentation; patients with delayed puberty
      spontaneously gained more than +2 SD score as adults. Recent reevaluations have
      concluded that short stature is not associated with clinically significant
      psychologic morbidity, and the psychologic outcome in response to growth hormone
      treatment of the short normal child showed no discernable difference in
      psychologic benefit, despite a difference in height gained. A recent editorial
      has strongly advised against the expanded use of growth hormone in the normal
      short child.

PMID- 9757369
TI  - Newer aspects of the pathophysiology, evaluation, and management of obesity in
      childhood.
AB  - Childhood obesity is a silent epidemic in America. Although most practicing
      pediatricians recognize clinically significant obesity and are aware of its
      potential morbidities, they often lack the tools to accurately quantify it, are
      rarely able to successfully treat it, and usually have no consistent approach to
      its prevention. In this update, recent information concerning the measurement,
      prevalence, natural history, complications, causes, evaluation, and management of
      childhood obesity is discussed.

PMID- 9757370
TI  - Aquaporin molecular biology and clinical abnormalities of the water transport
      channels.
AB  - In the past year, significant progress has been achieved in the research on
      aquaporins (AQPs), a family of structurally related molecular water channels.
      Three novel AQPs were identified, giving a total of ten mammalian AQPs. An
      important step forward in identifying the aqueous pore in AQP molecules was the
      determination of the three-dimensional structure of AQP1. The expression pattern
      of individual AQPs in different tissues was determined in more detail and AQP
      knockout mice have been generated. The discovery of a severe urinary
      concentrating defect in AQP1-knockout mice was remarkable. Only AQP2, the
      vasopressin-sensitive water channel in the kidney, which is mutated in autosomal
      recessive and dominant cases of nephrogenic diabetes insipidus, has been shown to
      be involved in human disease. The finding of changed AQP2 expression in several
      acquired water balance disorders may pave the way toward developing treatments
      for these clinical problems.

PMID- 9757371
TI  - Molecular biology and clinical importance of the Ca(2+)-sensing receptor.
AB  - The Ca(2+)-sensing receptor (CaR) is a member of the seven-transmembrane domain,
      G protein-coupled receptor super-family. In the parathyroid gland, it mediates
      the inhibitory effects of extracellular Ca2+ on the secretion of parathyroid
      hormone. In the kidney, activation of the CaR causes decreased reabsorption of
      Ca2+ from the tubular lumen. Mutations in the CaR gene produce abnormalities of
      Ca2+ homeostasis. Heterozygous loss-of-function mutations cause familial
      hypocalciuric hypercalcemia. Homozygous loss-of-function mutations cause neonatal
      severe hyperparathyroidism. In contrast, gain-of-function CaR mutations result in
      autosomal dominant and sporadic hypoparathyroidism. The resulting
      hypoparathyroidism and hypocalcemia can range from asymptomatic to life
      threatening. Patients with hypocalcemia due to CaR mutations also show
      disproportionate hypercalciuria that may increase the risk of nephrocalcinosis,
      nephrolithiasis, and renal insufficiency.

PMID- 9757372
TI  - Clinical utility of markers of bone turnover in children and adolescents.
AB  - We review the past years' literature on biochemical markers of bone turnover. A
      general introduction to markers of bone formation and bone resorption is followed
      by reference values of bone turnover in neonates, infants, and prepubertal and
      pubertal children. We describe intervention with calcium and physical activity in
      healthy children and bone turnover in patients. The predictive value of a single
      measurement of bone markers in individuals is poor, due to the large biologic
      intraperson variation for bone markers in general. Serious osteoporosis can be
      diagnosed by the combined results of measurement of several bone formation and
      resorption markers.

PMID- 9757373
TI  - Diabetes insipidus as a hallmark neuroendocrine complication of neonatal
      meningitis.

PMID- 9757374
TI  - Neonatal jaundice, animal-based injuries, and immunizations.
AB  - This review presents in a clinically relevant context the past year's
      investigations in three areas of pediatrics that commonly face the office-based
      pediatric provider. Although transcutaneous quantification of jaundice may help
      discern which patients warrant further evaluation, thereby saving patients pain
      and expense, this technology has not yet significantly changed clinical
      management of the hyperbilirubinemic infant. A brief overview of animal bites
      demonstrates that although most are innocuous, proper treatment of these
      potentially serious injuries is critical in preventing further complications. The
      number of immunizations given in the first 2 years of life has increased, and
      although new combination vaccines may eventually simplify the schedule,
      persistent vigilance is more important than ever to avoid delays in vaccine
      administration.

PMID- 9757375
TI  - [Ebstein's anomaly: when should a patient have operative treatment?].
AB  - Ebstein's anomaly is a complex malformation of the tricuspid valve where the
      hinges of the septal and/or posterior leaflets are displaced downward into the
      right ventricle. The leaflets show variable deformations. In general, the
      anterior leaflet is enlarged. For those patients who have only mild symptoms,
      medical management is recommended, but operative treatment is indicated if
      progressive deterioration is evident. The timing of the surgical intervention is
      still a matter of controversy, especially since the results of surgical treatment
      were substantially improved by further development of repair techniques. Between
      1974 and August, 1997, 69 patients with Ebstein's anomaly underwent surgical
      repair. In 65 patients (94.2%) tricuspid valvuloplasty was feasible, mainly by
      creating a monocusp valve with the "single-stitch technique", developed in our
      clinic by F. Sebening. Four patients required primary valve replacement with a
      bioprosthesis. Ten reoperations (14.5%) were necessary: 6 repeat valvuloplasties,
      4 valve replacements. There were 2 hospital deaths (2.9%), the late mortality was
      8.7% (6 patients). Since 1992, our valvuloplasties have been evaluated by
      intraoperative transesophageal echocardiography (TEE). Follow-up was obtained in
      58 patients (95%) over a period of 4 months to 21.0 years (median 5.3 years, mean
      7.6 years). The actuarial survival rate (Kaplan-Meier) was 96.5% +/- 2.4% at 1
      year and 83.3% +/- 5.6% at 21 years. Pre-operatively, the majority of patients
      were in New York Heart Association functional Class III. At follow-up evaluation,
      nearly all patients showed substantial improvement of their pre-operative status,
      94.8% were in NYHA Class I or II. Doppler echocardiographic studies demonstrated
      good tricuspid valve function in most patients. The valvuloplasty developed in
      our hospital using a single-stitch technique is a rewarding operation, which
      yields good long-term results. An analysis of the postoperative deaths revealed
      that all patients but one suffered from endstage cardiac disease and had a cardio
      thoracic ratio greater than 0.65. This supports the importance of surgical
      intervention in time. In our opinion, operation is even indicated for those
      patients in functional Class II who reveal clinical deterioration.

PMID- 9757376
TI  - [Pseudoaneurysm in the vicinity of the ascending aorta caused by contained
      disruption at the insertion site of a coronary artery bypass graft. A case
      report].
AB  - In this case report a 65-year-old patient came into the emergency ward with acute
      chest pain after coronary artery bypass graft operation in 1985. On routine chest
      X-ray in 1995 a mediastinal widening was diagnosed. The chest X-ray in 1997
      (Figure 1) showed an increase of the diameter of the known mediastinal widening.
      Therefore a CT-scan was performed (Figures 2a and 2b). This showed an enhancement
      of contrast material in a contained structure, without identifying its origin.
      Therefore a coronary angiography was done. Here, we diagnosed a contained
      disruption of the aorta at the insertion site of the bypass graft at the right
      coronary artery. Figure 3a shows leakage of contrast material out of the aorta
      into the pseudoaneurysm and in Figure 3b this is demonstrated in a schematic
      drawing. Figure 4a shows supraselective imaging of the pseudoaneurysm,
      demonstrated in a schematic drawing in Figure 4b. As the chest pain could only be
      handled by i.v.-medication, betablocker and bed rest we decided to operate. Intra
      operatively the diagnosis was confirmed (Figure 5a and 5b). Postoperatively the
      patient died due to cerebral ischemia. Despite the lethal outcome an operative
      revision appears even retrospectively justified because of the increasing size of
      the pseudoaneurysm in addition to new symptoms that were difficult to treat. On
      the other hand there are no data available in order to estimate the risk of a
      spontaneous course.

PMID- 9757377
TI  - [Angina pectoris in leiomyoma].
AB  - A 72-year-old patient presented himself with typical symptoms of coronary heart
      disease and was scheduled for invasive diagnostic procedures. Cardiac risk
      factors were smoking and arterial hypertension. The physical examination was
      inconspicious. In the laborchemistry a hemoglobin of 79 g/l with a mean
      corpuscular volume of 63 fl and a mean corpuscular hemoglobin of 20 pg was
      conspicuous. The serum iron was with 42 micrograms/dl in the lower norm.
      Transferrin, bili-rubin and lactate dehydrogenase were normal. Then in the
      gastrointestinal investigations he was diagnosed with a leiomyoma of the
      intestine that led to chronic anaemia and additionally to chest pain
      characteristic for angina pectoris. After the removal of the tumor and
      normalization of hemoglobin this patient was free from symptoms of the disease.
      The coronary angiography revealed a complex stenosis of the right coronary artery
      with collaterales and not significant stenosis both of the left coronary
      arteries. In patients with angina pectoris anaemia as the possible and only cause
      of angina ought to be verified. It is therefore necessary after normalization of
      hemoglobin and clarification of the cause for the anaemia to apply a test for
      coronary ischemia.

PMID- 9757378
TI  - Chest pain in cardiac syndrome X--caused by neuromuscular disorders?
AB  - We wanted to find out if chest pain in cardiac syndrome X can be a manifestation
      of neuromuscular disorders. Five patients with cardiac syndrome X (3 women, 2
      men), aged 34 to 70 years, consented with a clinical neurological examination,
      muscle enzyme testing, electroneurography of the right median and peroneal nerves
      and electromyography of the right brachial biceps and anterior tibial muscles. A
      neuromuscular disorder was found in 1 of the 5 investigated patients. The 60-year
      old man presented with a monoparesis of the left leg and sensory dysfunction of
      the left upper and lower limb. He was diagnosed as having either posttraumatic
      myelopathy or radiculopathy. Since chest pain in cardiac syndrome X can be caused
      by neuromuscular disorders, a comprehensive neurological examination is
      recommended in patients with this disorder.

PMID- 9757379
TI  - [Pleural and pericardial effusion after pacemaker implantation as first
      manifestation of malignant tumors].
AB  - We report 2 cases with unusual "complications" after pacemaker implantation. One
      patient developed hemorrhagic pleural and 1 patient pericardial effusion. Both
      manifestations of hemorrhage were felt to be due to complications in relation to
      the pacemaker implantation. However, in both patients cytologic analysis of the
      effusion revealed malignant cells, in 1 case from an ovarian cell carcinoma, in
      the other case from an adenocarcinoma of unknown origin. Our report indicates,
      that under rare circumstances pleural or pericardial effusion after pacemaker
      implantation may be the first manifestation of a malignant process independent of
      the pacemaker implantation procedure.

PMID- 9757382
TI  - [Sodium and water balance for clinical routine practice].

PMID- 9757381
TI  - [Pharmacoeconomic evaluation of pravastatin in the secondary prevention of
      coronary heart disease in patients with average cholesterol levels. An analysis
      for Germany based on the CARE study].
AB  - Those people who are to decide about health care systems are increasingly forced
      to identify unnecessary costs and achieve savings in health care. Especially for
      diseases with high prevalence like illnesses of the heart and the circulatory
      system preventive measures are very important. This economic analysis tries to
      clarify whether the secondary-preventive application of the HMG-CoA reductase
      inhibitor pravastatin is, apart from the clinical benefit, economically justified
      in patients suffering from coronary heart disease with average cholesterol
      levels. In the case of this study, the underlying type of economic evaluation was
      an incremental cost-effectiveness analysis. The outcome was defined as costs per
      life-year saved. This retrospective study is based on the results of the CARE
      (Cholesterol And Recurrent Events) study which has been published elsewhere [21].
      When calculating costs we took into account the perspective of 3rd party payers
      (public health insurance) in Germany. The calculation of cost-effectiveness was
      carried out for the whole study population in CARE as well as for all patients
      aged 60 or more years in the CARE study. This was done because the different
      groups vary by the numbers of avoided myocardial infarctions, strokes and loss of
      life years. Netcosts for pravastatin therapy, i.e. drug costs for pravastatin
      minus costs for avoided events, were about 9.54 Mio DM (referring to 1,000
      patients treated for a period of 5 years). Net-costs for patients aged 60 or more
      years were 8.18 Mio DM. The effectiveness was defined as the number of life years
      saved and amounted to 216 years of life saved (YOLS) in the overall study group.
      For patients aged 60 or more years we found that 358 years were saved. The costs
      per life years saved (i.e. the net-costs of pravastatin therapy divided through
      the number of life years saved) turned out to be 44,000 DM per person in the
      study group. For patients over 60 the costs were 23,000 DM. Lipid-lowering with
      pravastatin in the secondary prevention of coronary heart disease in Germany is
      cost-effective. In those patients aged 60 or more yeas the use of pravastatin is
      even more cost-effective than in all patients included in the CARE study.

PMID- 9757380
TI  - [Perforation and rupture of coronary arteries].
AB  - Spontaneous rupture of coronary arteries as well as coronary perforation during
      percutaneous interventions are rare but potentially life-threatening incidents
      often resulting in emergency surgery. Frequency of acute perforation due to
      therapeutic catheterization varies according to the devices employed. With
      conventional balloon angioplasty it is estimated to be 0.1 to 0.2% whereas
      substantially higher rates of up to 3% have been reported with the use of so
      called "new devices" (i.e. directional atherectomy, rotablation, excimer laser
      angioplasty or extractional atherectomy). Interventional strategies for
      nonsurgical treatment of acute coronary perforations during catheterization
      procedures have been developed. In recent times, availability of coronary stent
      grafts allows for a percutaneous resolution of acute perforations while
      maintaining vessel patency. Whereas iatrogenic perforations in the
      catheterization laboratory may thus be treated immediately at the site of their
      occurrence, rupture of pre-existing but potentially unknown coronary pathology
      frequently is associated with a diagnostic interval, giving rise to serious
      clinical events (i.e. myocardial infarction, cardiac tamponade, malign
      arrhythmias or sudden death). It may be warranted to advocate prophylactic
      treatment of rupture-prone coronary conditions even on incidental diagnosis. This
      can either be performed by cardiothoracic surgery or, in suitable cases, by
      interventional therapy. Implantation of coronary stent-grafts could prove to
      become the therapy of choice due to its technical facility, safety and the short
      length of hospital stay associated with it. Before general recommendations can be
      made, however, as to the extension of indication for these novel coronary
      devices, further clinical studies encompassing long-term clinical and
      angiographic follow-up are needed.

PMID- 9757383
TI  - [Disorders of potassium balance].

PMID- 9757384
TI  - [Disorders of magnesium balance].

PMID- 9757385
TI  - [Disorders of acid-base balance].

PMID- 9757386
TI  - [Disorders of calcium and phosphate homeostasis].

PMID- 9757387
TI  - [Disorders of trace element homeostasis].

PMID- 9757388
TI  - [Chronic diarrhea].

PMID- 9757389
TI  - [64-year-old patient with recurrent left orbital pseudotumor].

PMID- 9757390
TI  - [61-year-old patient with bronchiectasis, vitiligo and chronic atrophic
      gastritis].

PMID- 9757391
TI  - [HMG-CoA reductase inhibitors].

PMID- 9757392
TI  - [Detection of allergy to amalgam or other dental alloys].

PMID- 9757393
TI  - [Health risk caused by sugar substitutes].

PMID- 9757394
TI  - [Thrombocyte aggregation inhibition].

PMID- 9757395
TI  - [Drug interactions. Proton pump inhibitors. 1].

PMID- 9757396
TI  - [Measuring serum lipoproteins].

PMID- 9757397
TI  - [Liver transplantation in familial amyloid polyneuropathy].

PMID- 9757398
TI  - [Mycophenolate mofetil in comparison with other immunosuppressive drugs].

PMID- 9757399
TI  - [Comment on the contribution: Nikol S. et al. 51-year-old patient with reversible
      infarct-like ECG changes].

PMID- 9757400
TI  - Overview of special issue on adolescent suicide: risk, assessment, and treatment.
AB  - Regarding the pressing international health problem of adolescent suicide, the
      contributors to this special issue have provided new findings and perspectives
      around the theme of risk and its assessment. These contributions are summarized,
      and are viewed as examples of the reciprocal efforts of scientists and clinicians
      to systematize and deepen knowledge on adolescent suicide, and thus beneficially
      affect a pernicious health problem.

PMID- 9757401
TI  - A process model for assessing adolescent risk for suicide.
AB  - As the incidence of adolescent suicide within our society continues to rise, it
      becomes increasingly important for the mental health professional to be able to
      accurately assess suicide risk in adolescents who seek help. This process model
      discusses primary risk factors (previous attempt, affective disorders, and
      hopelessness), secondary risk factors (substance abuse and personality or
      behavioral disorders), situational risk factors (family functioning, suicide
      exposure, social support, life stressors, and homosexuality), and their combined
      implications and significance in determining an adolescent's level or risk for
      suicide. Use of both empirical data and clinical intuition are integrated to form
      a working client model that is continuously reassessed in four stages, guiding
      the mental health professional through a comprehensive assessment process.

PMID- 9757403
TI  - Suicidal ideation in an adolescent clinical sample: attachment patterns and
      clinical implications.
AB  - This study investigated the relationship between attachment patterns and suicidal
      ideation in a clinical sample of adolescents. Participants (n = 116) were
      assessed on level of current ideation through self-report questionnaires.
      Lethality of methods contemplated was also rated on a subset of the sample (n =
      16) who, in addition to endorsing current suicidal ideation, presented a plan on
      a diagnostic interview. Quality of attachment to care-givers based on a semi
      structured clinical interview was assessed using Bartholomew's two-dimensional,
      four-category model of attachment. Categorical analyses indicated that youth with
      predominantly fearful or preoccupied attachment were more likely to endorse
      suicidal ideation than were predominantly secure or dismissing youth. Severity of
      suicidal ideation was positively correlated with ratings of fearfulness and
      negatively correlated with ratings on the secure and dismissing patterns. Greater
      lethality in methods of contemplated suicide was positively correlated with
      preoccupied tendencies. The importance of attachment theory for understanding the
      factors underlying suicidal ideation in troubled youth is discussed and
      implications for therapeutic intervention are presented.

PMID- 9757402
TI  - Gender differences in rates and correlates of suicidal behaviour amongst child
      psychiatric outpatients.
AB  - Childhood suicide is an increasing problem in Western society. Identification of
      those at risk of suicidal behaviour is of priority to identify children with
      consequent mental suffering, and prevent successful attempts. The study
      determined factors associated with suicidal ideas, attempts or threats in 5426
      psychiatric outpatients aged between 8 and 17 years who attended a British
      teaching hospital. Multivariate logistic regression analyses were performed by
      sex on the data from the standard department questionnaire. Substance abuse,
      depression and disturbed relationships with adults were predictors of suicidal
      behaviour for both sexes. For female subjects, antisocial behaviour was also
      associated. In girls alone, depression had significant interaction effects with
      substance abuse and conduct disorder. Possible reasons for these differences are
      discussed.

PMID- 9757404
TI  - Reasons for living in a clinical sample of adolescents.
AB  - The psychometric properties and validity of the Reasons for Living (RFL)
      Inventory were examined in a sample of psychiatrically hospitalized adolescents
      (n = 253), aged 13 to 18 years, identified as suicide ideators, suicide
      attempters, and psychiatric controls. Confirmatory factor analysis suggested that
      the original RFL factors did not provide a good fit; exploratory factor analysis
      identified five factors, of which three were identical with the original RFL
      factors. Factor scores differentiated suicidal from non-suicidal adolescents and
      attempters from ideators. Correlational analyses indicated that RFL factors were
      associated with suicidal ideation, depression, and hopelessness, and predicted
      unique variance in suicidal ideation over that accounted for by depression and
      hopelessness. Our findings provide support for the RFL as a sound measure for
      clinical and research assessment in adolescents.

PMID- 9757405
TI  - The relationship between lethality of attempted suicide and prior suicidal
      communications in a sample of residential youth.
AB  - Some type of suicidal communication precedes 80% of attempted and completed
      suicides in adolescents. This study investigates the relationship between the
      number of suicidal communications prior to an attempt and the lethality of the
      attempt in a sample of adolescent youth residing in a residential treatment
      facility. The sample consisted of 46 youth who had a suicide attempt while in a
      large group home residential facility over a 9-year period. Results indicated
      that attempters who made fewer suicidal communications beforehand tended to use
      more lethal methods in their attempts. Attempters with two or more preceding
      suicidal communications had significantly lower lethality in their attempts than
      did those with fewer suicidal communications. Few differences emerged between the
      groups in regards to demographic or psychosocial variables.

PMID- 9757406
TI  - Negative life events and adolescent suicidal behavior: a critical analysis from
      the stress process perspective.
AB  - In the present review we examine empirical evidence concerning relationships
      between negative life events and adolescent suicidal behavior. Separate critical
      analyses were made for suicidal ideation, suicide attempts and completed suicide,
      suggesting common and differential aspects. Although there is evidence supporting
      the hypothesis that life events may comprise a risk factor for adolescent
      suicidal behavior, their contribution tends to be moderate or weak. A problem
      with past research is that it has not adequately incorporated mediating and
      moderating variables into pathways that link psychosocial stressors and suicidal
      outcomes. A stress process model is presented as a possible alternative to better
      understanding the relationships between stress and suicide, and to provide a
      conceptual and heuristic framework for future research.

PMID- 9757407
TI  - Suicidal ideation and acts of self-harm among Dublin school children.
AB  - The purpose of this study is to ascertain rates of suicidal ideation and self
      harm in a classroom population of 13- and 14-year-old children using a screening
      questionnaire and to confirm accuracy of these screening results by home
      interview. There were significant differences between suicidal ideation rates at
      screening and at home interview (44% vs. 29%) and between self-harm rates (8% vs.
      2%). Those with suicidal ideation at home interview believed more in a "right to
      suicide" and believed suicidal ideation to be more widespread among adolescents.
      School factors were believed by respondents to be important in the causation of
      adolescent suicide. Fewer than one-fifth would advise consultation with a
      psychiatrist to a suicidal friend.

PMID- 9757409
TI  - Family predictors of suicidal symptoms in young adolescents.
AB  - A 1-year longitudinal study tested the model that the relation between maternal
      depression and adolescent suicidal symptoms is mediated by family functioning.
      Participants were 240 children (mean age = 11.86 years) and their mothers; 77% of
      the mothers had a history of a mood disorder and the remaining 23% were lifetime
      free of psychopathology. An adolescent suicide index was created based on suicide
      items from the child and parent versions of the Children's Depression Inventory,
      Child Behavior Checklist and Children's Depression Rating Scale, administered at
      both Time 1 and 2. Family functioning was assessed with the Family Relationship
      Index completed by mothers and children at Time 1. Results indicated that the
      relation between maternal depression and adolescent suicide symptoms at Time 2
      was mediated by perceived family functioning, controlling for suicide symptoms at
      Time 1.

PMID- 9757408
TI  - Screening for suicidal ideation in children and adolescents: methodological
      considerations.
AB  - The prevalence of suicidal ideation and attempts varies considerably depending on
      (a) who the reporters are for youth suicidality, (b) the degree of retrospection
      required, and (c) the type of measure used to assess suicidality. The purpose of
      this study is to examine some of the methodological issues that should be
      considered when administering suicidal screening measures to children and
      adolescents. The risk group was comprised of offspring of depressed mothers (26
      mothers with Bipolar Disorder, 42 mothers with Major Depressive Disorder). The
      comparison group was comprised of offspring of mothers without past or current
      psychiatric diagnosis (30 mothers). Two siblings from each family were recruited
      for participation (n = 192). Screening for youth suicidality was based on (a)
      structured diagnostic interviews with youth (yielding interval and lifetime
      reports), (b) youth self-reports, and (c) maternal reports. Assessments were made
      when the younger siblings were approximately 6, 9, and 14 years of age and older
      siblings were approximately 6, 9, 13, and 18 years of age. Mothers reported a
      lower prevalence of youth suicidal content than did youth. Discrepancies between
      mother and child report were more common in the risk group. When lifetime
      retrospection of suicidal content was assessed, fewer youth reported suicidal
      thoughts or actions than when suicidal content was assessed approximately every 3
      years. Also, the prevalence of self-reported suicidal content was somewhat higher
      (7 to 13%) than when assessing suicidality within the context of an interview.
      Child and maternal characteristics were found to correspond to patterns of
      consistent and discrepant reporting.

PMID- 9757410
TI  - Family rigidity, adolescent problem-solving deficits, and suicidal ideation: a
      mediational model.
AB  - Family rigidity and adolescent problem-solving deficits have each been linked to
      adolescent suicidal behaviors. The objective of the present study was to evaluate
      the hypothesis that family rigidity has primarily an indirect effect on
      adolescent suicidal ideation through its effect on adolescent problem-solving
      deficits. College students and their parents completed the Family Adaptability
      and Cohesion Evaluation Scale II. Students also completed the Problem-Solving
      Inventory and the Adult Suicidal ideation Questionnaire. Structural equation
      models confirmed that family rigidity has an indirect effect on adolescent
      suicidal ideation through its effect on adolescent problem-solving deficits.
      Directions for treatment efforts are discussed.

PMID- 9757411
TI  - Suicidality and cognitive vulnerability to depression among college students: a
      prospective study.
AB  - Using a behavioral high-risk two-site prospective design, we tested the cognitive
      vulnerability hypotheses about suicidality. Consistent with prediction, the high
      cognitive risk (HR) participants were more likely than the low cognitive risk
      (LR) participants to exhibit suicidality, measured by both structured diagnostic
      interview and questionnaire self-report, during the 2 1/2 year prospective follow
      up period. Moreover, when the prospective period was examined as a whole, the
      mediation hypothesis derived from the cognitive theories was strongly supported.
      Hopelessness appeared to mediate the obtained relationship between cognitive
      vulnerability and suicidality. Finally, the obtained relationship between
      cognitive vulnerability and suicidality was not mediated by other hypothesized
      risk factors for suicidality not specified in the cognitive theories, such as
      past suicidality, personal history of depressive disorders, borderline and
      antisocial personality dysfunction, and parental history of depression.

PMID- 9757412
TI  - An integrative conceptual framework for assessing and treating suicidal behavior
      in adolescents.
AB  - Suicidal adolescents represent a uniquely demanding clinical population.
      Regardless of psychotherapeutic orientation, the existing standards of care
      demand a relatively broad and integrative approach with multiple and specific
      treatment targets, as well as ongoing and repeated risk assessment. The current
      article provides an integrative conceptual framework for these tasks in day to
      day clinical practice with essentially two goals: (1) to provide a summary of
      therapeutic and assessment tasks (i.e. the content of therapy and assessment)
      consistent with existing standards of care and supported by empirical findings,
      and (2) to emphasize the varied roles, tasks, demands and limitations of
      psychotherapy with suicidal adolescents.

PMID- 9757413
TI  - Adolescent suicide risk today: a paradox.
AB  - A review of international statistics indicates that youth suicide rates are not
      increasing in all nations. Furthermore, it is suggested that the quality of life
      in nations is improving and that this improvement itself may increase the risk of
      suicide, especially in youth with narcissistic personality traits and antisocial
      personality disorder traits.

PMID- 9757415
TI  - [Non-epileptic paroxysmal movement disorders].
AB  - Non-epileptic paroxysmal dyskinesias present with different forms of
      extrapyramidal hyperkinesias (dystonia, chorea, athetosis, ballism) in variable
      combinations and with cerebellar signs, respectively. They may be classified as:
      1. paroxysmal dystonias/choreoathetoses (paroxysmal dystonic choreoathetosis =
      PDC), paroxysmal kinesigenic choreoathetosis = PKC, intermediate form) and 2.
      paroxysmal ataxias (PA) (PA with myokymia and neuromyotonia, azetazolamide
      responsive PA). Nocturnal paroxysmal dystonia is now regarded as one form of
      nocturnal frontal lobe epilepsy. Research in molecular genetics has substantially
      contributed to the etiologic understanding of paroxysmal dyskinesias: In
      different families linkage has been successfully completed for PDC (chromosome
      2q) and PA (chromosomes 12p, 19p). PA are now identified as channelopathies with
      mutations in the potassium channel (PA with myokymia and neuromyotonia) and the
      calcium channel gene (azetazolamide-responsive PA).

PMID- 9757414
TI  - [S100B: pathogenetic and pathophysiologic significance in neurology].
AB  - S100B is a multifunctional member of the S100-calmodulin-troponin superfamily of
      proteins and can modulate the activity of other intracellular proteins following
      binding of calcium. S100B has been shown to exhibit regulatory effects on cell
      growth and differentiation as well as on cell shape and energy metabolism. S100B
      has neurotrophic properties and stimulates glial cell proliferation in vitro and
      in vivo. Overexpression of S100B has been proposed as a pathogenetic factor in
      plaque formation in patients with Alzheimeris disease and Down syndrome.
      Furthermore, S100B-specific T-lymphocytes have been shown to be encephalitogenic
      in the animal model of experimental autoimmune panencephalitis (EAP).
      Phenotypically and functionally similar S100B-specific T-cells can also be
      recovered from the peripheral blood of humans making S100B a potential candidate
      autoantigen in multiple sclerosis. Here the basic biochemical, molecular and
      functional properties of S100B are reviewed with special regard to the potential
      pathogenetic role of S100B in Alzheimeris disease, Down syndrome and multiple
      sclerosis.

PMID- 9757416
TI  - [X-chromosomal recessive spinobulbar muscular atrophy (Kennedy type). Description
      of a family, clinical aspects, molecular genetics, differential diagnosis and
      therapy].
AB  - The Kennedy-Syndrome is a X-linked recessive bulbospinal muscular atrophy, in
      some cases associated with endocrinological disturbances such as androgen
      resistance and diabetes mellitus. The age of onset is usually between 20 and 40.
      Presenting symptoms are proximal flaccid weakness, fasciculations, cramps or
      tremor. Disease progression is usually slow and live expectancy is normal. It is
      important to distinguish the Kennedy-Syndrome from amyotrophic lateral sclerosis,
      spinal muscular atrophy, muscular dystrophies and other types of motor neuron
      disease. Kennedy disease is caused by an expanded trinucleotide repeat in the
      androgen receptor gene. Genetic analysis allows a precise-diagnosis on an
      individual basis and reliable genetic counselling. An effective medical treatment
      does not yet exist.

PMID- 9757417
TI  - [Influence of the Esmarch splint on chewing and tongue muscle activity during
      sleep].
AB  - To clarify the functional mechanism of the Esmarch device in the treatment of
      sleep apnea, its effect on muscle activity during sleep was studied
      electromyographically with and without the appliance at the inferior head of the
      lateral pterygoid muscle, the genioglossal muscle, and the masseter muscle in 15
      patients with sleep apnea syndrome. During the obstructive apnea the muscles
      showed significantly lower amplitudes than before the apnea. No significant
      decrease in the amplitude was observed during the central apnea, but, after the
      obstructive and central apnea, significantly higher amplitudes were seen than
      beforehand. The amplitudes rose after the placement of the appliance, and the
      amplitudes of the genioglossal and lateral pterygoid muscles during obstructive
      apnea increased significantly after the insertion of the appliance. The results
      suggest that the device can activate the masticatory and tongue muscle activity
      and indicate that the muscles activated with the appliance can prevent
      obstruction in the oropharynx. The Esmarch device not only helps avoid
      obstruction by mandibular protraction, but also affects function by activating
      the muscles.

PMID- 9757418
TI  - [Clinical application of transcranial color-coded duplex ultrasound for detection
      of intracranial aneurysms].
AB  - We investigated 88 Patients with a total of 102 angiographically diagnosed
      intracranial aneurysms by means of transcranial colour coded Duplex sonography
      (TCCD) during a time period of 15 months. Both the size and the localization of
      the aneurysms were determined. Seventy aneurysms (77%) with a diameter of 16 +/-
      8 mm (6-55 mm) were detectable, with excellent visualization in 36 (42%),
      moderate visualization in 34 (40%), and no sufficient visualization in 16 (16%)
      aneurysms, respectively. In another 16 cases (16%) there was no sufficient vone
      window. Thrombotic material inside the aneurysm was detectable in 16/20 cases
      (75%), visualization of coil embolized aneurysms in 12/25 patients (48%). TCCD
      allows the follow up of cerebral aneurysms, with the detection of thrombosis and
      treatment effects after embolization. The method is not valid for the detection
      of intracranial aneurysms.

PMID- 9757419
TI  - [Systemic thrombolysis with plasminogen activator in chronic stroke patients].
AB  - Following the study protocol, we stratified the 615 patients of ECASS I according
      age (< or =/-70 years) and analysed the response to intravenous rt-PA in both
      subgroups. The older patients (248) suffered from the same stroke severity as the
      younger patients (367) experienced, however, a more severy clinical course
      (placebo group after 3 months after stroke: Barthel Index 50 vs. 85, mortality
      24% vs. 11%). Treatment with rt-PA increased the proportion of undisabled
      patients at 3 months after stroke onset significantly only in the younger
      patients. The risk for brain parenchymal hemorrhage was increased by the factor
      of 4.7 and 4.6 in both age groups. It is obviously harder to achieve an
      undisabled state by systemic thrombolysis in the elderly. Facing the risk of
      brain hemorrhage associated with rt-PA, the risk-benefit-ratio may be less
      favourable in patients over 70 years.

PMID- 9757420
TI  - [Diffusion-weighted imaging in acute stroke].
AB  - Magnetic resonance imaging represents today the most important tool in
      neuroradiology for both clinical practice and research. MRI allows imaging of the
      human body in 2 or 3 dimensions with variable tissue contrast. The natural
      diffusion of tissue protons can now be used as a supplementary contrast
      mechanism. Different MRI techniques can be used to obtain clinically useful
      diffusion-weighted images. These techniques all require the use of strong
      gradient pulses in order to obtain the diffusion contrast. In the current
      article, the most important physical principles of diffusion measurement are
      presented. After a short introduction into the basic physical principles, we will
      present the prerequisites and limitations of clinically relevant applications
      today. Finally a few select examples of clinical use of these techniques in the
      acute diagnosis of stroke will be presented.

PMID- 9757421
TI  - [Value of antibody titers for diagnosis of neuroborreliosis].
AB  - Neuroborreliosis is a very frequent subtype of infection with Borrelia
      burgdorferi. Because of the widely spread inapparent infections finding of
      diagnosis by analysis of serum antibodies is very difficult. In the years 1990
      1994 the serum of 6.775 patients of the Department of Neurology in Homburg,
      Germany was analysed with regard to Borrelia burgdorferi specific IgG antibodies.
      24% showed a positive serum titer and 20% a borderline result. 73 patients showed
      a specific intrathecal IgG antibody synthesis. In contrast to patients with
      antibodies in serum these patients showed a significant cumulation during summer.
      The high percentage of positive serum titers and the season independence support
      the assumption of widely spread inapparent infections. If a patient shows
      neurological symptoms the finding of serum antibodies against Borrelia
      burgdorferi is not sufficient for the diagnosis of Neuroborreliosis. A specific
      intrathecal synthesis of antibodies, is the most reliable serological indicator
      for Neuroborreliosis. Intrathecal synthesis usually starts three to four weeks
      after the first clinical symptoms.

PMID- 9757422
TI  - [Schizophreniform psychosis with polydipsia and electrolyte imbalance in multiple
      sclerosis].
AB  - We present the case report of a young woman who suffered from schizophrenia-like
      psychosis leading to polydipsia and consequent water intoxication. Because of
      progressive somnolence and epileptic seizures therapy on the intensive care unit
      became necessary. Findings of MRI and cerebrospinal fluid were consistent with
      the diagnosis of chronic inflammatory disease of the central nervous system. As
      other possible causes could be excluded, multiple sclerosis seemed to be most
      probable. Simultaneous incidence of schizophrenia and multiple sclerosis and the
      differential diagnosis of central pontine myelinolysis following hyponatremia are
      discussed.

PMID- 9757423
TI  - [A rare cause of peracute vision loss: pseudotumor cerebri. Case report of course
      with recurrence after decompression of the optic nerve].
AB  - In primary pseudotumor cerebri (PTC) intracranial pressure is elevated by so far
      unknown mechanisms. There is a wide range of clinical courses. Therapy is
      controversial. We present a case of PTC with acute visual loss. After optic nerve
      sheath decompression a relapse occurred. A 30-year old female patient experienced
      visual loss within 48 h accompanied by headache and slight neck stiffness. Visual
      acuity was 1/50 in the right eye; in the left eye just hand movements and light
      were perceived. Fundoscopy revealed a 9 dptr. prominent optic disc bilaterally.
      After optic nerve sheath decompression (ONSD) she improved, but underwent a
      relapse after 3 months. Twenty-four-hour measurement of intracranial pressure
      revealed elevated values. As a consequence ventriculo-peritoneal shunting was
      performed, leading to prominent improvement. Primary PTC can cause acute visual
      loss. If conservative treatment fails, different surgical procedures should be
      considered.

PMID- 9757424
TI  - [MRI findings in Wernicke encephalopathy].
AB  - Wernicke's encephalopathy (WE) is a consequence of vitamin B1 (thiamine)
      deficiency and in the majority of cases due to alcoholism. We report here the
      case of a 26-year-old male alcoholic who had stayed helplessly at home for 4 days
      until hospital admission. Clinical diagnosis was difficult due to major
      disturbance of consciousness. MRI showed an increase in signal intensity (T2-,
      FLAIR-weighted) around the third ventricle, the quadrigeminal bodies, the
      fornices, the mamillary bodies, the floor of the fourth ventricle and around the
      aqueduct. These findings were indicative of WE although of unusual extent. In
      this case MRI correlated well with clinical symptomatology. Therapy with thiamine
      was started immediately and symptoms as well as MRI findings resolved partially.
      The presented case illustrates the diagnostic usefulness of MRI in WE especially
      if the patient is of reduced consciousness and clinical investigation is limited.

PMID- 9757425
TI  - [Ictal syncopes. Cardiac sympathetic innervation disorder as the etiology?].
AB  - We report 3 cases of an ictal sinus arrest. All patients suffered from temporal
      lobe epilepsy (TLE). Seizures were monitored with simultaneous video-eeg during
      preoperative epilepsy diagnosis. One patient with cortical dysplasia, who
      frequently suffered from long lasting syncopes, had a nearly completely missing
      cardiac sympathetic innervation in MIBG-SPECT (=Meta-Iodide-Benzyle-Guanidine
      single-photon-emission tomography). Cardiac investigation including long-term ECG
      and echocardiography had shown normal findings. After epilepsy surgery the
      syncopal events in all patients disappeared. A dominant parasympathetic ictal
      stimulus following excitation of the reticular formation might cause the ictal
      bradycardia and sinus arrest. A missing sympathetic innervation, possibly
      occurring as fehlbildung together with cortical dysplasia, which makes
      autoregulation impossible, might then be the explanation for sudden cardiac ictal
      death.

PMID- 9757426
TI  - [HMG-CoA reductase inhibitor and risk of stroke].
AB  - HMG-CoA reductase inhibitors are potent cholesterol-lowering drugs. Recent
      clinical trials and meta-analyses show a 30% stroke reduction after treatment
      with HMG-CoA reductase inhibitors. Subgroup analyses and experimental findings
      support the notion that HMG-CoA reductase inhibitors improve endothelial function
      directly by mechanism(s) independent of cholesterol-lowering. They reduce
      inflammatory, proliferative and thrombogenic processes in atherosclerotic plaques
      and improve endothelial dysfunction. Recent findings demonstrate an enhanced
      production of endothelium-derived nitric oxide (NO) by HMG-CoA reductase
      inhibitors. Endothelial NO is an important vasodilator and plays a beneficial
      role in cerebral ischemic injury. Prophylactic treatment with HMG-CoA reductase
      inhibitors in mice selectively upregulates endothelial NO synthase expression and
      activity, increases cerebral blood flow at resting state and during ischemia, and
      reduces cerebral infarct size after experimental stroke. These findings provide a
      novel mechanism for the prophylactic treatment of ischemia-induced cerebral
      injury under non-hypercholesterolemic conditions.

PMID- 9757427
TI  - [Special presentation on the 90th anniversary of organizing the German Society of
      Neurologists in Dresden on 14 December 1907].

PMID- 9757428
TI  - [Neurology in the "3rd Reich" and consequences].
AB  - This review of German neurology during the Nazi era mentions first the
      significance of Jewish neurologists for the history of the specialty, and the
      irreplaceable loss that their expulsion from Germany represented. A brief
      discussion of the scientific accomplishments of German neurologists during this
      time is followed by a description of violations of ethical principles,
      exemplified by the human experiments of G. Schaltenbrand. The spirit of the age
      exerted a malevolent influence.

PMID- 9757429
TI  - History of the surgical treatment of epilepsy.

PMID- 9757430
TI  - The diagnosis of the epileptic focus.

PMID- 9757431
TI  - Temporal lobe epilepsy.

PMID- 9757432
TI  - Dysembryoplastic disorders in neoplastic and non-neoplastic process associated
      with temporal lobe epilepsy.

PMID- 9757433
TI  - Lesionectomy in surgical treatment of epilepsy.

PMID- 9757434
TI  - Multilobar resections in surgical treatment of medically intractable epilepsy.
AB  - MATERIAL, METHOD: Authors present the results of surgical treatment in a series
      of 93 patients with medically intractable epilepsy and large epileptogenic foci,
      in whom multilobar resections have been performed. They constituted 13% of a
      group of 716 patients subjected to surgery due to drug resistant epilepsy in the
      period 1957-1996, in the Department of Neurosurgery, Medical University of
      Warsaw, Poland. Patients treated with multilobar resection constituted the group,
      characterised by the most severe course of epilepsy, so they usually had a long
      seizures' history at the time of operation (more than 10 years duration of the
      disease in 37% of patients), albeit they were qualified to surgery at a
      relatively young age (mean age at the time of surgery: 16-th year of life).
      Trauma was the most frequent underlying aetiologic factor (perinatal trauma and
      other major head injury were documented in 28% and 30% of patients respectively).
      Morphological abnormalities of the resected brain tissue were found on
      pathological examination (light microscope) in 68% of patients in this series.
      RESULTS: Perioperative mortality was 3%. At a follow-up examination (mean follow
      up period 7 years postoperatively): 30% of patients were seizure free, in 13% of
      patients drug discontinuation was possible. In 23% of patients less than 2-3
      seizures per year occurred. So totally in 53% of patients, good result of
      treatment was achieved (none or only very rare seizures). In 35% of patients
      surgery failed to control seizures' frequency. 9% of patients were lost from
      follow-up evaluation. CONCLUSIONS: Multilobar resection (if acceptable from the
      clinical point of view) may be an effective treatment choice in patients with
      medically uncontrollable seizures and huge epileptogenic foci. This treatment
      modality may offer recovery from seizures or significant improvement to 53% of
      patients treated. The radical removal of epileptogenic foci, age of the patients
      higher than 18 year of life at the time of operation, focal character of EEG
      abnormalities and occurrence of only one type of seizures, were found to be good
      prognostic factors. On the other hand younger age of the patients operated, the
      presence of generalized slow waves in the interictal EEG recordings and the
      occurrence of various types of seizures, influenced adversely on the prognosis.

PMID- 9757435
TI  - Classical hemispherectomy in treatment of severe form of epilepsy: an analysis of
      surgical interventions performed in first years of surgical management of sacred
      disease.

PMID- 9757436
TI  - Frontal lobe epilepsy: symptomatology and results of surgical treatment.

PMID- 9757438
TI  - Kozevnikov's epilepsy--epilepsia partialis continua (results of surgery in 11
      patients).

PMID- 9757437
TI  - Surgical treatment of intractable parietal lobe epilepsy--our own experience.

PMID- 9757440
TI  - Occipital lobe epilepsy.

PMID- 9757439
TI  - Chronic drug resistant symptomatic epilepsy starting in early childhood.

PMID- 9757441
TI  - Callosotomy in patients with drug-resistant epilepsy.

PMID- 9757442
TI  - Cerebellar electrostimulation in patients with drug-resistant epilepsy.

PMID- 9757443
TI  - Changes of the quality of life after anterior callosotomy.

PMID- 9757444
TI  - CBF evaluation before and after ketamine or brietal activation of the epileptic
      discharges.

PMID- 9757445
TI  - [The value of structural neuroimaging in the selection of patients for epileptic
      surgery].
AB  - The aim of this study was to investigate the value of structural neuroimaging
      with MRI in the selection of patients for epilepsy surgery. We sought to
      determine whether MRI influenced decision concerning resective surgery and
      whether MRI provided much more useful information than enhanced CT. MATERIALS AND
      METHODS: Neuroimaging studies, MRI and CT, of 300 patients; 265 with partial and
      35 with primary generalized seizures, evaluated for surgical treatment of
      epilepsy were analysed. The MRIs and CTs were interpreted using visual diagnostic
      criteria and findings were correlated with the EEG changes and clinical
      semiology. RESULTS: MRIs identified structural lesions in 142, CTs in 96 of all
      patients. The clinical semiology (partial seizures), MRI, CT and EEG focal
      findings were concordant in 72 cases. The group of 34 patients had resective
      surgery. The 7 patients were also operated with MRI and CT focal abnormalities
      discordant with EEG changes. Also one patient with primary generalized epilepsy
      and temporal lobe lesion (glioma) had resective surgery. MRI studies revealed
      structural lesions in 48 patients with normal CT studies. The 43 patients with
      partial epilepsy had normal CTs and lesions in MRIs; the 34 cases revealed
      correlation with the EEG findings in 29 temporal and 5 extratemporal regions.
      Surgery were performed in 23 cases. Also one with partial seizures and MRI
      detected hippocampal atrophy was operated, despite of generalized EEG patterns.
      In contrast CT revealed two patients with normal MRI and focal changes. The
      patients with partial seizures and only CT abnormalities (focal calcifications)
      were not operated due to discordant EEG findings. In group of 132 patients with
      normal neuroimaging studies and EEG identified seizure focus only 27 had anterior
      temporal lobectomy. CONCLUSION: MRI studies gave additional information in case
      of 16% patients with intractable epilepsy in comparison with CT findings.
      Resective epilepsy surgery was almost twice as often performed when MRIs revealed
      structural abnormality. In operated patients, diagnostic sensitivity of
      structural MRI, CT and EEG to neurophatology were 70.6%, 46.7 and 92.4%
      respectively.

PMID- 9757446
TI  - Diagnostic significance of all night physiological sleep EEG records in patients
      with drug resistant focal epilepsy.

PMID- 9757447
TI  - [The comparison of ketamine with methohexital and thiopental in the
      intraoperative EEG in drug-resistant epilepsy].
AB  - The acute (ECoG) was examined in 291 patients with intractable epilepsy, without
      structural brain lesion--from 1971 to 1997. Temporal lobectomy was performed in
      198 cases and extratemporal (frontal, parietal or occipital) in remaining 93
      cases to achieve seizure control. Epileptic foci was activated during acute ECoG
      by i.v. administration of ketamine (154 cases) or short-acting barbiturates-
      methohexital (110 cases) and thiopental (27 cases). RESULTS: Ketamine
      significantly more often caused ECoG identified electrographic seizures than
      methohexital: p = 0, 00001 or thiopental, which in no cases resulted in seizures.
      Also electrographic seizures occurred more frequently after administration of
      ketamine in patients with the extratemporal seizure focus localisation in
      comparison with temporal focus (p < 0.05). Electrographic seizures provoked after
      administration of ketamine improved the localisation of the area to be resected,
      more often in extratemporal epileptic foci. CONCLUSIONS: The results of our
      investigations indicate that ketamine more effectively activated epileptic focus
      than short-acting barbiturates.

PMID- 9757449
TI  - The cortical distribution of somatosensory potentials evoked by median nerve
      stimulation in patients with epilepsy treated by surgery.

PMID- 9757448
TI  - A comparison of Wada test for cerebral speech dominance by use of amytal or
      brietal.

PMID- 9757450
TI  - The influency of frontal lobectomy on motor pattern in epileptic patients
      (Preliminary report).

PMID- 9757451
TI  - Difficulties in outcome assessment in surgically treated patients with epilepsy.

PMID- 9757452
TI  - Pharmacotherapy of focal epilepsy after surgical treatment.

PMID- 9757453
TI  - [Molecular biology of antibodies].

PMID- 9757454
TI  - [Indirect anastomoses for moyamoya disease].

PMID- 9757455
TI  - [In vitro study on intrathecal application of 5-fluoro-2'-deoxyuridine (FdUrd)
      for meningeal dissemination of malignant tumor].
AB  - To evaluate the possible clinical intrathecal use of 5-fluoro-2'-deoxyuridine
      (FdUrd) for malignant brain tumors, its anti-tumor activity and neurotoxicity
      were compared with that of 5-fluorouracil (5-FU) and 5-fluorouridine (FUrd) in
      vitro. FdUrd showed good tumoricidal activity against cultured mouse 203 glioma
      cells and rat Walker 256 carcinoma cells as well as A172 human glioblastoma
      cells. Daoy human medulloblastoma cells and CADO-LC4 human lung cancer cells. It
      also showed less toxicity for primary cultures of neurons from C57/BL6 mouse and
      human embryo compared to 5-FU and FUrd. Thymidine phosphorylase (TPase) and
      thymidine kinase (TK), key enzymes for metabolism of 5-FU derivatives, were
      measured in cerebrospinal fluid (CSF). TPase or TK activity was detected in the
      CSF of hardly any patients with malignant brain tumors including meningeal
      carcinomatosis. These data indicated that the CSF is a favorable site for FdUrd
      chemotherapy, because the rate of conversion of FdUrd injected to 5-FU would be
      minimal. In conclusion, FdUrd may be potentially useful for intrathecal treatment
      of meningeal carcinomatosis.

PMID- 9757456
TI  - [Changes in QOL in patients with brain tumors measured by mood changes during and
      after treatment].
AB  - Patients with brain tumors are exposed to severe stress which may have an
      influence on their quality of life (QOL). To measure QOL in those patients, we
      measure their mood state during and after the treatments. MATERIALS: 16 patients
      who were admitted to our department for treatment of brain tumors, were included
      in the study. The tumors included 5 gliomas, 6 meningiomas and others. They were
      7 males and 9 females, and age distributed from 19 to 74 years old. All patients
      presented more than 90% of the Karnofsky performance score (KPS) on discharge, so
      they were expected to return to their previous social life. METHOD: The self
      answering tests were performed on admission (Pre), on discharge (Post 1), and at
      more than 5 months after the discharge (Post 2). The tests included an original
      questionnaire asking consent to admission and treatment, and concerning the
      feeling of disability to cope with conditions of living, Cornell Medical Index
      (CMI) which measured the neurosis, and Profile of mood state (POMS) which
      measured the 6 subscales of patients mood states including tension-anxiety (TA),
      depression (D), anger-hostility (AH), vigor (V), fatigue (F), and confusion (C).
      RESULTS: The questionnaire showed that the patients feel satisfied with having
      consented to the treatment. The feeling of disability to cope with living became
      stronger in Post 2 than in Pre. CMI showed a borderline of neurosis in three
      patients on admission, and in four patients in Post 2. Only the TA of POMS
      subscale improved significantly in Post 2. However, other subscales were
      unchanged. It is characteristic that all of the subscales of POMS showed less
      disturbance on discharge compared with that on admission, but, they returned to
      the Prelevel after they returned to social life. CONCLUSIONS: Patients with brain
      tumors have satisfactory consent to the treatment, however, they feel disability
      to cope with social life. On discharge, they showed a better mood state compared
      to that on admission, but the mood state turned for the worse again during the
      follow-up period. It is evident that patients with brain tumors are exposed to
      severe stress even after the completion of the treatment. The results necessitate
      our taking patients' mental health into consideration for our treatment protocol.

PMID- 9757457
TI  - [Extradural temporopolar approach for giant pituitary adenomas invading the
      cavernous sinus and parasellar regions].
AB  - OBJECTIVE: An extradural temporopolar approach has recently been used in the
      treatment of the parasellar, infrachiasmatic, or intracavernous regions. In this
      approach, the temporal (superficial) dural layer is separated from the deep layer
      (inner cavernous membrane) to expose the cavernous sinus extradurally. We report
      our experiences with 5 cases in which a giant pituitary adenoma invading the
      cavernous sinus and parasellar regions was resected via the extradural
      temporopolar approach. PATIENTS AND METHODS: Between January 1995 and December
      1997, 60 patients with pituitary adenomas were operated on at Okayama University
      Hospital. The extradural temporopolar approach was used for 5 patients who had a
      giant pituitary adenoma invading the cavernous sinus and parasellar regions. The
      5 patients were women aged from 32 to 62 years and presented with a visual
      dysfunction. Four patients had hormonally non-functioning pituitary adenomas and
      one had a growth-hormone secreting pituitary adenoma. RESULTS: The operations
      resulted in 1 total, 3 subtotal and 1 partial removal. There was no operative
      mortality or major morbidity. Transient oculomotor palsy occurred in 2 cases
      postoperatively. This approach provided excellent exposure of the tumor, relevant
      cranial nerves and arteries in and around the cavernous sinus through extradural
      retraction of the temporal lobe, allowing for sufficient resection of the
      intracavernous and parasellar portion of the tumor. Tumors invading the inferior
      portion of the clivus or the contralateral cavernous sinus could not be removed
      through this approach. CONCLUSION: Our findings suggest that the extradural
      temporopolar approach is useful for resection of giant pituitary adenomas
      invading the cavernous sinus and parasellar regions.

PMID- 9757458
TI  - [Visual acuity outcome and recurrence in large or huge pituitary adenomas
      operated with transcranial approach: comparison between frontotemporal and
      interhemispheric approaches].
AB  - Pituitary macroadenomas which required transcranial removal were reviewed
      concerning visual acuity outcome as well as recurrence. We encountered 173
      pituitary adenomas of which 27 (15.6%) were removed transcranially during the
      past 13 years. Eight cases were excluded due to inadequate information and
      improper utilization. Thus, a total of nineteen cases were reviewed in which the
      frontotemporal (FT) approach was utilized for seven cases and the
      interhemispheric (IH) approach for 12 cases. The mean size and volume of the
      tumors in the FT group were 3.0 x 3.7 x 3.1 cm and 18.2 cm3. The main reason for
      utilizing this approach was the fact that the tumors extended laterally involving
      the unilateral cavernous sinus or that unilateral preoperative visual acuity was
      obstructed. The visual acuity outcome was as follows: In six cases showing useful
      visual acuity on both sides before surgery, no apparent aggravation on either
      side was found in four cases, while in two cases there was complete obstruction
      on the operative side. The remaining case showed aggravation on both sides,
      though the approach side was decided upon because of the obstructed vision on
      that side. The mean size and volume of the tumors in the IH group were 4.6 x 4.8
      x 4.9 cm and 71.1 cm3. This approach was used due to the extreme suprasellar
      extension because of the large size of the tumors. Although the tumors were
      relatively large and the visual acuity was assessed as fair prior to surgery,
      visual acuity showed no significant deterioration after the operation and was
      found to be satisfactory in 11 out of 12 cases. The complications in the FT group
      were oculomotor palsy in 3 cases, hemorrhage in one case, and frontal infarction
      in one case. On the other hand, three cases suffered hemorrhage in the tumor
      cavity of the IH group, though none needed surgical evacuation. Most of the cases
      in the IH group showed pituitary hypofunction following the surgical removal of
      the tumors as compared to the cases in the FT group. Recurrence had occurred, in
      some cases, several years after the operation. Furthermore, some of the tumors
      are still growing larger following only partial or subtotal removal. The prime
      aim of the treatment for huge pituitary adenomas which require the transcranial
      removal is to retain as much visual acuity as possible. In conclusion, the IH
      approach has been shown to be preferable in this situation. The FT approach was
      found to be more dangerous in terms of visual outcome than had been expected,
      even if the tumors were not particularly large.

PMID- 9757459
TI  - [Can EC-IC bypass prevent brain ischemia from recurring?].
AB  - The effectiveness of extracranial-intracranial arterial bypass (EC-IC bypass)
      surgery for patients with hemodynamic compromise still remains controversial. In
      the present study, we evaluated the correlation between the pre- and post
      surgical cerebral hemodynamics and long-term prognosis. 28 patients and a
      subsequent 21 patients (41 men, eight women: mean age 59.9 [S.D. 8.6] years) with
      reduced cerebrovascular reserve due to steno-occlusive disease of the cerebral
      major arteries formed the study groups 1 and 2, respectively. Measurement of the
      mean hemispheric cerebral blood flow (mCBF) and the cerebral vasoreactivity
      (%mCVR) with an intravenous acetazolamide injection were performed by a 133Xe
      inhalation method and SPECT. Patients were treated with EC-IC bypass surgery and
      measurement of mCBF and %mCVR were made again about one month after surgery. The
      patients were observed for a long period (mean 44.3 months). During the follow-up
      period, 6 patients experienced recurrent ischemic strokes. The annual incidence
      of recurrent ischemic stroke was 4.4%. The patients with significantly reduced
      pre- and post-surgical resting mCBF of the affected hemisphere were at
      significantly higher risk of recurrent ischemic stroke than the patients with
      normal mCBF (p < 0.01). The %mCVR of the affected hemisphere rose after surgery.

PMID- 9757460
TI  - [Report of four cases of lymphocytic infundibuloneurohypophysitis].
AB  - We reported 4 cases of lymphocytic infundibuloneurohypophysitis. All four
      patients had diabetes insipidus as initial symptoms without anterior pituitary
      dysfunction. All patients showed pituitary stalk swelling and two patients showed
      enlargement of the pituitary gland. No patients were operated on for a
      histological diagnosis. No patients received corticosteroid treatment for this
      pathology. The mean follow-up period was 36 months. The diabetes insipidus
      continued in all cases, but radiological findings showed improvement in all
      cases. In one case, adrenal insufficiency occurred after 10 months, but had
      disappeared 6 months later. We think lymphocytic infundibuloneurohypophysitis can
      be diagnosed without histological examinations and can be treated conservatively
      without corticosteroid treatment. It seems to be a self-limiting disease. This
      disease can be distinguished from lymphocytic adenohypophysitis, but in some
      cases, both the anterior and posterior pituitary glands are invaded, and in this
      situation lymphocytic hypophysitis may be an appropriate name. Even if the
      initial symptom is diabetes insipidus, careful follow-up is needed for the
      duration of the disease.

PMID- 9757462
TI  - [Molecular mechanisms of axonal transport].

PMID- 9757461
TI  - [Primary intracerebral malignant fibrous histiocytoma with adhesion to a dura: a
      case report].
AB  - A case of malignant fibrous histiocytoma (MFH) in a 29-year-old man was reported.
      CT scans revealed an iso density mass which was homogeneously enhanced by
      contrast medium. MRI demonstrated that the right frontal tumor showed slight low
      signal intensity in T1-weighted image, and iso signal intensity in T2-weighted
      image. Gadolinium-enhanced T1-weighted image showed a homogeneously enhanced
      multinodular tumor. Right carotid angiogram revealed a tumor stain fed by the
      precentral artery. On operation, en-bloc resection was performed successfully.
      Postoperatively, local irradiation of 60Gy was performed. Microscopically,
      fibroblast-like cells arranged in storiform pattern were observed, and bizarre
      multinucleated giant cells were also observed. Ki-67 labelling index was 54%. We
      considered the tumor was a MFH and arose from an intracerebral mesenchymal
      tissue. We reviewed some literature and briefly discussed clinicopathological
      features and therapy of intracranial MFH.

PMID- 9757464
TI  - [MR axonography: application of MRI].

PMID- 9757463
TI  - [Evaluation of axonal transport].

PMID- 9757465
TI  - [Diseases with axonal flow impairment].

PMID- 9757466
TI  - [Gene transduction for experimental brain tumors using recombinant adenovirus
      vector].
AB  - Recent advances in molecular biology have permitted significant progress toward
      the treatment of malignant brain tumors using gene transduction methods.
      Adenovirus vectors have recently been shown to transduce genes successfully into
      brain tumor cells both in vitro and in vivo. We have investigated the feasibility
      of gene transduction for brain tumors using adenovirus vectors. To evaluate in
      vitro transduction rate by adenovirus vectors, rat 9L gliosarcoma cells or human
      glioblastoma cells were infected with recombinant replication-deficient
      adenovirus vectors containing the E. coli beta-galactosidase gene (Adex-CALacZ)
      and stained with X-Gal. We observed a multiplicity of infection (MOI)-dependent
      rate. Approximately 100% transgene expression was achieved at a MOI of 5 after
      seven days of incubation. To evaluate transgene expression in a rat brain tumor
      model, AdexCALacZ was stereotactically injected into established rat 9L brain
      tumors. Intratumoral injection of AdexCALacZ resulted in high transgene
      expression in tumor cells. Although injection of AdexCALacZ in the normal basal
      ganglia resulted in broad and diffuse transduction into endogenous neural cells,
      direct intratumoral injection resulted in transduction that was relatively
      restricted to the tumor cells as well as some neighboring normal cells.
      Transduction rates were relatively elevated at the margin of the tumor. Our
      results suggest that adenovirus vectors might be a feasible method to transfer
      therapeutic genes into malignant brain tumors.

PMID- 9757467
TI  - [Superior sagittal sinus thrombosis presenting with subarachnoid hemorrhage in a
      patient with aplastic anemia].
AB  - A 54-year-old female, who had been treated for aplastic anemia by metenolone
      acetate since 1981, developed a sudden unconsciousness in September 1995. On
      admission, she was drowny, CT showed a subarachnoid hemorrhage (SAH) in the right
      Sylvian fissure. Angiography demonstrated a complete occlusion of the superior
      sagittal sinus. The SAH was assumed to be originated from rupture of the right
      Sylvian vein, which was irregularly dilated on angiography. The dural sinus
      thrombosis was thought to be caused by a long term use of metenolone acetate, and
      it was discontinued. But her platelet count dropped due to the aggravation of
      aplastic anemia, and she developed repeated hemorrhagic infarction. An active
      anticoagulant therapy for the dural sinus thrombosis was thought to be
      inappropriate because she had the aplastic anemia and the hemorrhagic infarction
      recurred. We have successfully treated this case by mild anticoagulant therapy
      with nafamostat mesilate (Futhan).

PMID- 9757468
TI  - [A case of impending neuroleptic malignant syndrome associated with Shy-Drager
      syndrome].
AB  - We report a 55-year-old man with impending neuroleptic malignant syndrome who
      showed a remarkable dysautonomia such as dysuria and was treated with L-dopa
      under the diagnosis of Shy-Drager syndrome. The patient demonstrated fever,
      leukocytosis and elevated serum creatine kinase by a decrease in L-dopa dose.
      Probably, he developed impending neuroleptic malignant syndrome, induced by
      urinary tract infection as well as decrease in L-dopa dose. Since Shy-Drager
      syndrome is often treated with antiparkinsonian drugs, neuroleptic malignant
      syndrome can possibly develop after the change in dosage of catecholaminergic
      drugs. The imbalance of neurotransmitters and receptors in the central autonomic
      nervous system may participate in the development of neuroleptic malignant
      syndrome. Accordingly, Shy-Drager syndrome can easily be associated with
      neuroleptic malignant syndrome because of its severe disturbance in the autonomic
      nervous system. However, autonomic nervous dysfunction, a major sign of
      neuroleptic malignant syndrome, might be masked by symptoms of Shy-Drager
      syndrome. Therefore, diagnosis of neuroleptic malignant syndrome is often
      delayed. Careful observations of patients with Shy-Drager syndrome related with
      an antiparkinsonian drug are necessary, especially when the dose of drugs is
      changed or the general condition deteriorates.

PMID- 9757469
TI  - [Usefulness of aspiration surgery for elderly patients with hypertensive
      cerebellar hemorrhage].
AB  - We report two cases with hypertensive cerebellar hemorrhage who were successfully
      treated with frameless stereotaxic aspiration. First case, an 85-year-old man
      with hypertension had a large-sized hematoma in left cerebellar hemisphere.
      Emergency aspiration for cerebellar hemorrhage was carried out through a
      suboccipital burr hole. He had a good recovery at discharge. Second case, an 84
      year-old female with hypertension showed right cerebellar hemorrhage. She had
      been in somnolence state for one month with conservative treatment. Then,
      aspiration surgery for the hematoma was carried out through a suboccipital burr
      hole. Her neurological condition was ameliorated. Frameless stereotaxic
      aspiration for cerebellar hemorrhage through suboccipital burr hole is less
      invasive and useful procedure, especially for elderly patients.

PMID- 9757471
TI  - [A case of measles encephaloneuropathy in a pregnant women].
AB  - We reported a patient with measles encephaloneuropathy. A 26-year-old woman in
      her 15th week of gestation became febrile and developed cutaneous eruption
      typical of measles on July 1 1997. Five days after appearance of the rash, fetal
      death was identified and the fetus was removed. Following the operation, she
      became comatous. Neurological examination revealed neck stiffness, flaccid
      paralysis of the four limbs, and decreased sweating in the lower limbs. CSF
      protein was 143 mg/dl with cell count of 1365/mm3. Myelin basic protein in CSF
      was positive. High titers of antimeasles antibodies were found in the serum and
      the cerebrospinal fluid. EEG revealed a predominance of slow waves. In MRI
      obtained earlier in her illness, high signal intensity areas were noted to spread
      in the brain stem and external capsule on T2-weighted images. However, T1
      weighted image was unremarkable. Serial electrophysiological studies suggested
      demyelination of the motor nerves. With combination of methylprednisolone and
      immunoglobulin therapy, she made a remarkable recovery without any neurologic
      sequelae. We believe that the measles encephalitis in our patient is
      predominantly demyelinating due to an immunologic reaction in a
      pathophysiological aspect. We should pay attention to coincident poly
      radiculoneuropathy in the early stage of measles encephalopathy.

PMID- 9757470
TI  - [A case of glioblastoma manifesting 49 years after lobotomy].
AB  - We report a case of glioblastoma manifesting 49 years after a lobotomy. He was
      diagnosed as having schizophrenia at age 20 and was operated on with a standard
      lobotomy when he was 27 years old. He had led a useful life after 40 years old
      without medication. Because of hallucination and delusion, he was hospitalized at
      the end of 1996. CT showed a well enhanced tumor adjacent to the cavity made by
      the lobotomy in the left frontal lobe. This is the second case report of
      glioblastoma just beside the cavity formed by lobotomy. The relationship between
      glioblastoma and old lobotomy is discussed, especially in regard to morphology
      and CT findings.

PMID- 9757472
TI  - [A case of neurologic type of Wilson's disease with increased aluminum in liver:
      comparative study with histological findings to metal contents in the liver].
AB  - Histological findings and metal contents in the liver were studied in a patient
      with neurologic type of Wilson's disease. Copper and aluminum contents in the
      biopsied liver of the patient with Wilson's disease were measured simultaneously
      by neutron activation analysis at Research Reactor Institute, Kyoto University.
      Four cases of adult cirrhosis were selected as the control for cirrhosis and five
      cases of adult liver as the control for neurologically normal. The biopsied liver
      showed markedly increase in the copper content (814.4 micrograms/g: dry weight)
      and extremely high content of aluminum (479.4 micrograms/g: dry weight), compared
      to those of the controls. On the other hand, macroscopically no cirrhosis was
      observed and the characteristic appearances of macronodular cirrhosis failed to
      detect histologically. Interestingly the fibrosis or inflammation of the liver
      was seen faintly. It is likely that toxic metals in the liver such as aluminum,
      copper and manganese might be implicated in the pathogenesis of neurologic type
      of Wilson's disease.

PMID- 9757473
TI  - [Kernohan notch].

PMID- 9757474
TI  - [Radiologic emergency management in multiple trauma cases].
AB  - The management of multiple trauma patients has improved recently. Surgeons'
      education, preclinical rescue structures, initial clinical survey and therapeutic
      strategies, as well as diagnostic imaging, have progressed. Plain film imaging is
      increasingly being abandoned in favor of CT. Fast imaging techniques (spiral CT)
      have led to the inclusion of CT in the primary survey. To minimize the risk to
      the patient during prolonged diagnostic time, algorithms have to be defined
      concerning structures, emergency room equipment and quality. Basics, state of the
      art and suggestions concerning management of multiple trauma patients are
      presented and discussed from the radiologist's point of view.

PMID- 9757475
TI  - [Diagnostic imaging of acute head and brain injuries].
AB  - The role of neuroimaging in the acute setting of head trauma is to diagnose the
      extent of intracranial injury and to identify all lesions which require urgent
      neurosurgical treatment. Computed tomography (CT) remains the most important
      diagnostic tool for initial screening of trauma victims. Although magnetic
      resonance imaging (MR) has higher sensitivity to most traumatic lesions than CT,
      due to the ease and speed of CT, and the fact that sufficient monitoring of
      critically ill patients during the examination is much easier with CT than with
      MR, mean that MR is not the imaging modality of choice for the initial diagnostic
      work-up. Recent MR techniques such as FLAIR or diffusion imaging further improve
      the sensitivity of MR in head trauma. Conventional angiography is currently
      indicated only for few suspected vascular lesions (e.g. traumatic arterio-venous
      fistulas, vascular dissections).

PMID- 9757476
TI  - [Trauma of the facial bones and skull].
AB  - Facial trauma is frequent and mainly caused by motor vehicle accidents. Due to
      this main etiologic factor, trauma to the facial skeleton is often associated
      with serious injuries, commonly involving the brain, chest or abdomen. As a
      consequence, the initial clinical management of these patients includes control
      of hemorrhage and immediate assessment of life-threatening injuries, including
      the maintenance of the airways. Patients presenting with facial trauma are
      initially evaluated with a systematic clinical examination because many fractures
      can be accurately diagnosed by inspection and palpation alone. In these cases
      plain film radiographs serve only for confirmation and documentation of the
      diagnosis. In many other cases accompanying and extensive soft tissue swelling
      may clinically obscure fractures. A complete and accurate evaluation of these
      patients requires additional radiological imaging methods. A series of plain
      films may be generally sufficient but in most of the cases they can be regarded
      as initial screening methods for more thorough diagnosis with computed tomography
      (CT). In trauma patients CT is the imaging method of choice because it shows more
      fracture lines and displaced fragments than any other imaging modality. CT
      delineates soft tissue and bony structures and can localize and even characterize
      foreign bodies. A complete and accurate characterization of the fracture type and
      potentially associated complications in mandatory for the appropriate treatment
      and can only be achieved by careful radiological (CT) evaluation.

PMID- 9757477
TI  - [Spiral CT and conventional CT in the preoperative imaging of intraocular metal
      foreign bodies].
AB  - PURPOSE: To compare the effectiveness of spiral CT versus conventional CT in the
      preoperative assessment of metallic intraocular foreign bodies. METHODS: Eighteen
      patients with penetrating eye injuries and suspected metallic intraocular foreign
      bodies were assigned to undergo either spiral CT or conventional CT in the axial
      plane. The spiral and the conventional CT data were transferred to a workstation,
      and reconstructions in the coronal and sagittal planes were performed. Additional
      direct coronal scanning was performed only when necessary for preoperative
      assessment. The quality of the axial as well as the reconstructed coronal and
      sagittal images was assessed for each imaging modality. The size of the foreign
      bodies was measured and compared to the actual diameter. Total examination time
      and radiation dose delivered to the lens were measured for each imaging modality.
      RESULTS: All foreign bodies were detected by each scanning modality on the axial
      and on the reconstructed planes. The quality of the axial images was similar for
      spiral and conventional CT. The spiral technique provided high-quality
      reconstructed images which allowed accurate localization of the foreign bodies in
      all cases. Reconstructions by conventional technique were inadequate for
      preoperative assessment. The examination time for the total orbital volume was 18
      s for spiral CT and 52 s for conventional CT. Radiation dose delivered to the
      lens was 35 mGy for spiral CT and 56 mGy for conventional CT axial scanning.
      CONCLUSION: Spiral CT multiplanar imaging offers several significant advantages
      for the preoperative assessment of metallic intraocular foreign bodies compared
      to the conventional CT technique in clinical practice, including short
      examination time, minimized motion artifacts, reduced radiation exposure, and
      accurate localization.

PMID- 9757478
TI  - [Spinal trauma].
AB  - In the workup of patients suffering from spinal trauma the radiologist is eager
      to make a proper diagnosis asking only for few additional examinations. This can
      be done by a functional and biomechanical approach in reading standard
      radiographs. With the knowledge of the kind of injury expected the whole extent
      of posttraumatic changes in the spine can be delineated exactly. The goal is to
      make a diagnosis that answers questions of stability so the traumatologist can be
      aided in therapy.

PMID- 9757479
TI  - [Radiologic imaging of thoracic trauma].
AB  - Blunt trauma to the chest results from the transfer of kinetic energy to the
      human body. It may cause a wide range of mostly life-threatening injuries,
      including fractures of the thoracic skeleton, disintegration of the pleural
      space, contusion or laceration of pulmonary parenchyma and damage to the
      mediastinal structures. For a systematic approach it may be helpful to follow an
      organ-based evaluation of thoracic trauma. However, it should be borne in mind
      that subtle injuries may be associated with serious complications. Trauma to the
      chest may affect different anatomic compartments at the same time, requiring an
      extending diagnostic approach. Conventional radiography plays a major role in
      diagnosing thoracic trauma, complemented by ultrasound examination of the pleura
      and abdomen. It is well documented that CT scanning represents a major
      technological improvement for assessment of thoracic trauma. With the advent of
      fast helical CT scanning this method becomes more applicable for severely
      traumatized patients and potentially replaces other time-consuming procedures.
      State-of-the-art imaging of both projection and cross-sectional techniques
      provides useful information for immediate and appropriate treatment mandatory in
      patients with thoracic trauma.

PMID- 9757480
TI  - [Radiologic diagnosis of abdominal trauma].
AB  - In Europe ultrasonography has displaced diagnostic peritoneal lavage (DPL) in the
      primary survey of polytraumatized patients with suspected abdominal trauma.
      Hemodynamically unstable patients who are brought to the emergency room with
      blunt abdominal trauma will go directly to the operating room after a rapid
      ultrasonography examination with evidence of hemoperitoneum. In hemodynamically
      stable patients, in addition to ultrasonography, computed tomography can be done.
      This is especially efficient if evaluation with sonography is not completely
      possible or shows little pathology (e.g. small amounts of hemoperitoneum).

PMID- 9757481
TI  - [Pelvic ring injuries].
AB  - PURPOSE: Analysis of the trauma patient of fractures of the pelvic ring and
      classification according to AO/Tile. METHODS: 125 unselected patients (43
      females, 82 males) were evaluated retrospectively by conventional x-ray, and CT
      examinations included follow-studies. RESULTS: Type-A fractures were seen in 36
      (29%), Type-B fractures in 58 (46%), and Type-C fractures in 31 (25%) cases. Type
      B and Type-C fractures mainly occurred in patients with traffic accidents and
      falls from great height. Type-A fractures were seen most often in patients with
      accidents at home or at work. However, in patients with complex fractures a
      classification concerning Type-B or Type-C fractures was difficult. SUMMARY:
      Based on CT criterias, in most patients a statement concerning the applied
      forces, the stability of the pelvic rim and the fracture type can be made.

PMID- 9757482
TI  - [High-flow priapism following blunt perineal trauma. Interventional therapy].
AB  - A 10-year old boy developed an arteriocavernosal fistula with a permanent penile
      erection (high-flow priapism) after a blunt perineal trauma. The diagnosis was
      established by Doppler ultrasound, blood gas analysis and angiography. A
      conservative treatment attempt with penile cooling and puncture of the cavernosal
      corpera with blood aspiration and etilefrine instillation failed to resolve the
      priapism. An embolization of both bulbocavernosal arteries was followed by an
      immediate detumescence. Normal functional erection was preserved. No recurrence
      was observed during a follow-up of 6 months.

PMID- 9757483
TI  - [Unclear shoulder pain].

PMID- 9757484
TI  - [Acceptance: scientific cultural aspects].
AB  - In highly developed industrial societies the acceptance of risk is in decline.
      The reasons for this are connected in elementary fashion with the fact of modern
      life. Their effects may be considered irreversible, and pep talks under the motto
      "dare to risk!" are probably of no avail; we must adapt ourselves to declining
      risk acceptance. What are the reasons for it?

PMID- 9757485
TI  - [Evaluation of respiratory muscles].
AB  - Respiratory muscle weakness may be the sole cause of dyspnea or may aggravate
      dyspnea due to another respiratory disease, and is often difficult to recognise
      clinically. The assessment of respiratory muscles should follow a graded approach
      using tests of increasing complexity. Clinical examination should look for
      dyspnea, orthopnea, morning headache, daytime somnolence, fatigability,
      tachypnea, abdominal, or rib cage paradox, and amyotrophy. Imaging is useful in
      diagnosing diaphragmatic paralysis using chest radiograph, fluoroscopy or
      ultrasound. In cases of moderate to severe respiratory muscle weakness, lung
      volumes show reduced vital capacity and total lung capacity. Measuring the change
      in vital capacity from sitting to supine position is useful since it shows a 25
      50% fall in cases of diaphragmatic paralysis. The specific and classical tests of
      respiratory muscle strength are maximum inspiratory and expiratory pressures (MIP
      and MEP) sustained during one second against near complete occlusion. Sniff nasal
      inspiratory pressure (SNIP) is a new and easier test of inspiratory muscle
      strength. Normal values obtained with these simple tests rule out clinically
      significant respiratory muscle weakness. In case of doubt, more complex and
      invasive tests can be used such as transdiaphragmatic pressure and magnetic
      stimulation of the phrenic nerves.

PMID- 9757486
TI  - ["Multiple chemical sensitivity syndrome"].
AB  - Multiple chemical sensitivity (MCS) has been described as an acquired multiple
      organ disease typically characterized by central nervous irritative and/or
      gastrointestinal symptoms. Advocates of this suspected syndrome attribute these
      disorders to overstressing of the organism caused by exposure to external noxae.
      Opponents of the theory of MCS attribute all the symptoms to classical
      conditioning or other psychopathological processes. In so far as controlled data
      exist, there is no indication of a toxic or immunological cause for this
      syndrome.

PMID- 9757487
TI  - [Aerosol therapy].
AB  - Aerosol therapy plays a major role in the diagnosis and treatment of various lung
      diseases. The aim of inhalation therapy is to deposit a reproducible and adequate
      dose of a specific drug to the airways, in order to achieve a high, local,
      clinical effect while avoiding serious systemic side effects. To achieve this
      goal, it is therefore important to have an efficient inhalation device to deliver
      different medications. However, the currently available therapeutic inhalation
      devices (nebuliser, pressurised metered-dose inhaler and dry powder inhaler) are
      not very efficient in aerosol delivery and have several disadvantages. Inhalation
      devices can be assessed by in vitro studies, filter studies and radiolabelled
      deposition studies. Several radiolabelled deposition studies have shown that
      nebulisers and pressurised metered-dose inhalers are not very efficient in
      aerosol delivery. In children, before 1997, only 0.5% to 15% of the total
      nebulised or actuated dose from a nebuliser or pressurised metered-dose inhaler
      actually reached the lungs. These numbers were somewhat improved in adults, 30%
      of the total nebulised or actuated dose reaching the airways. Aerosol therapy
      with dry powder inhalers was the most efficient before 1997, 30% of the total
      dose being deposited in the lungs of adults and children. In 1997, new
      developments in pressurised metered-dose inhalers much improved their efficiency
      in aerosol delivery. Lung deposition can be increased by up to 60% with use of a
      non-electrostatic holding chamber and/or a pressurised metered-dose inhaler with
      a hydrofluoroalkane propellant possessing superior aerosol characteristics.
      Several studies comparing the clinical efficiency of different inhalation devices
      have shown that the choice of an optimal inhalation device is crucial. In
      addition to the aerosol characteristics, ventilation parameters and airway
      morphology have an important bearing on deposition patterns. These parameters may
      be greatly influenced by the patient's acceptance of a specific inhalation device
      and therefore determine the choice of the device used. It is important for the
      clinical impact to develop more efficient inhalation devices, which need to be
      assessed for use in different age groups. These devices should be cheap, easy to
      use, portable, usable with all medications and environmentally safe.

PMID- 9757488
TI  - Bronchiectasis.

PMID- 9757489
TI  - [Morbid obesity: 130 consecutive patients with laparoscopic gastric banding].
AB  - Morbid obesity causes co-morbidity such as diabetes mellitus, hypertensive heart
      disease, sleep apnoea, degenerative bone diseases and increased incidence of
      malignancy. Life expectancy and quality of life are reduced significantly.
      Without adequate weight loss, treatment of co-morbidity remains symptomatic only.
      Surgical treatment of morbid obesity is the one therapy promising long-term
      success, since conservative procedures normally lead to recurrence of overweight.
      We performed laparoscopic gastric banding on 130 patients between 1.11.95 and
      31.10.97. Mean overweight was 63 +/- 12.7 kg (SD), and mean BMI was 46.5 +/- 4.6
      kg/m2. The average hospital stay was 5.5 +/- 1.5 days. 4 patients with
      postoperative pulmonary embolism were treated with oral anticoagulation. We
      performed 9 (6.9%) reoperations because of pouch dilatation or dorsal slipping
      with food intolerance in the first series of 70, and none in the second series of
      60 patients. Median weight loss after 3 months was 14.7 +/- 4.2 kg, after six
      months 24.0 +/- 6.6 kg and after 12 months 33.2 +/- 8.5 kg, corresponding to
      excessive weight loss (EWL) of 55.9 +/- 14.8% in the first year. 14 (70%) of 20
      patients with diabetes mellitus normalised and 6 patients with diabetes mellitus
      normalised and 6 patients showed improved blood sugar levels. All 36 patients
      with hypertensive heart disease had normalised blood pressure, 60% of them
      without further medical antihypertensive treatment after median EWL of 36%.
      Cholesterol levels normalised in 30 (57%) patients and improved in 20 (38%) after
      6 months. Laparoscopic gastric banding is a suitable method for reducing weight
      in morbid obesity patients and provides a better quality of life in a group of
      patients who are carefully evaluated and followed. Reducing co-morbidity and
      improving ability to work have a positive economic impact on health care costs.

PMID- 9757490
TI  - [Molecular physiology and pathophysiology of renal phosphate excretion].
AB  - The kidney is a key organ in phosphate homeostasis. Phosphate excretion is
      largely determined by free glomerular filtration and by regulated reabsorption in
      the proximal tubule. The cellular/molecular mechanisms involved in phosphate
      reabsorption have been elucidated in great detail over the past few years. A
      brush border membrane protein with most probably 8 membrane-spanning regions
      represents the rate-limiting and physiologically/pathophysiologically modified
      transport mechanism. Altered phosphate reabsorption correlates with an altered
      brush border membrane transporter protein content, altered either by new
      synthesis/membrane insertion or by membrane retrieval/degradation. Current
      knowledge on the molecular/cellular level is a prerequisite for an understanding
      of kidney based alterations in phosphate homoeostasis.

PMID- 9757491
TI  - [ 40 years of 5-fluorouracil--still an attractive cytostatic].
AB  - On its 40th birthday 5-fluorouracil (FU) is still an attractive drug frequently
      employed in adjuvant and palliative treatment of colorectal and breast cancer,
      head and neck cancer, oesophageal cancer and anal cancer. After all this time it
      is still not known what the optimal schedule or the best form of administration
      is, and whether or not modulation of the drug is of any benefit. This article
      deals with the drug's different modes of action depending on the schedule of
      administration. An overview of the literature on drug modulation is given. We
      introduce the less well-known side effects of the drug and the newly developed
      orally administered prodrugs of FU.

PMID- 9757492
TI  - [Extrinsic allergic alveolitis: a review for the practitioner].
AB  - Extrinsic allergic alveolitis (EAA) or hypersensitivity pneumonitis (HP) is a
      clinical syndrome characterised by an inflammatory, partly granulomatous, immune
      disorder involving interstitial and alveolar spaces secondary to inhalation of
      organic substances. The disorder is mainly due to occupational exposure, farmer's
      lung being the best-known example. Acute, subacute or chronic forms can be
      clinically differentiated. Given the fact that chronic forms may present a
      pattern of irreversible pulmonary fibrosis, clinicians must be aware of the
      diagnosis of EAA in every situation where the history shows a potential antigenic
      exposure. Prevention should be reinforced by increasing individual protective
      measures and by improving techniques used at the workplace.

PMID- 9757493
TI  - [Farmer with osteomalacia?].

PMID- 9757494
TI  - Implementing the North Karelia Project in Scotland.
AB  - A comprehensive, determined and theory-based community programme can have a
      meaningful and positive effect on risk factors and life styles. In much the same
      way as the North Karelia Project was rolled out to cover the whole of Finland,
      there is no reason why our intervention schemes could not be rolled out to cover
      the whole of Scotland. The North Karelia Project proved that a major national
      demonstration programme can be a strong tool for favourable national development
      in chronic disease prevention and health promotion.

PMID- 9757495
TI  - Falls in old age: inevitable or preventable?

PMID- 9757496
TI  - Medical schools in the new millennium.

PMID- 9757497
TI  - Scottish Hypothermia and Rewarming Project (SHARP)

PMID- 9757498
TI  - Minor morbidity after day-case surgery.

PMID- 9757499
TI  - The dangers of taking 'T in the country'.
AB  - 'T in the Park' is the largest annual music festival in Scotland. This paper
      reports on how an increased attendance and change of location for the 1997 event
      altered the workload. The influences that affected the pattern of patient
      presentations and the adaptations made in the medical service provided are
      discussed.

PMID- 9757500
TI  - Neutralising IL-12 activity as a strategy for prolonging allograft survival and
      preventing graft-versus-host disease.
AB  - Interleukin-12 (IL-12) is a key immunoregulatory cytokine which promotes the
      development of Thl-dependent, cell-mediated immune responses. Acute allograft
      rejection after organ transplantation and acute graft-versus-host disease (GVHD)
      after bone-marrow transplantation are generally attributed to cell-mediated
      immune mechanisms and, therefore, potentially susceptible to immunological
      intervention at the level of IL-12. Recent data from murine models of
      transplantation have highlighted the potential of IL-12 as a selective target for
      immunotherapy. Neutralising endogenous IL-12 for a brief period at the time of
      transplant promotes long-term deviation from a Th1 to a polarised Th2 alloimmune
      response. This confers lasting protection from GVHD but is less effective at
      preventing acute rejection, possibly because Th2-dependent immune responses are
      also capable of effecting graft rejection.

PMID- 9757501
TI  - A retrospective epidemiological analysis of non-accidental head injury in
      children in Scotland over a 15 year period.
AB  - A retrospective analysis of the epidemiological characteristics of non-accidental
      head injury (NAHI) in children in Scotland over the last fifteen years from 1981
      until March 1996 was performed. The information was provided by the Information
      and Statistics Division of the Scottish Health Service. The average incidence of
      NAHI calculated over this period was 0.04 cases per year per 1000 children under
      5 years. Fifty-five per cent of all cases occurred in those children who were
      less than a year old. 41% of cases were inflicted by a parent but in 47% the
      perpetrator could not be identified. The mortality rate was found to be 2%. Non
      accidental head injury cases identified using the ICD-9 coding classification
      system gives a surprisingly low incidence. This number is probably an
      underestimate and the reasons for this are discussed. A prospective
      epidemiological analysis of NAHI in children in Scotland is being undertaken to
      determine the true incidence.

PMID- 9757502
TI  - Early diagnosis of hepatocellular carcinoma in haemochromatosis influences
      surgical management.
AB  - Using case note review, a retrospective analysis was carried out of all patients
      referred with haemochromatosis and suspected hepatocellular carcinoma between
      1988 and 1997 to define the mode of presentation, management and outcome of such
      patients. All 12 patients were male with a mean age of 67 years. Four patients
      presented whilst asymptomatic by alpha-fetoprotein screening. Mean time interval
      between diagnosis of haemochromatosis and hepatocellular carcinoma was 6.7 years.
      One patient underwent right hepatectomy, seven patients were treated by
      chemoembolisation and the remaining four patients were treated symptomatically.
      The median survival of the chemoembolised patients was 13 months. Of those
      patients treated symptomatically, the median survival was four months. Screening
      for hepatocellular carcinoma is often not undertaken in patients with
      haemochromatosis. Survival prospects are poor in patients whose tumour presents
      symptomatically.

PMID- 9757503
TI  - Visual loss in a returning traveller with tick typhus.
AB  - Rickettsial diseases are increasingly found world-wide and should be considered
      in febrile patients returning from abroad. This case report describes the
      vasculitic complications of a patient returning from the Republic of South Africa
      with tick typhus.

PMID- 9757504
TI  - A melange of meningiomata.
AB  - Eight case reports of elderly patients with meningiomata are presented. Their
      mode of presentation to a typical district general hospital in central Scotland
      and subsequent clinical management is described. The significance of these cases
      is discussed.

PMID- 9757505
TI  - The witch doctors of Scotland.
AB  - To investigate beliefs about healing in early modern Scotland, records of 61
      witch trials were examined. Thirty-three were found to include healing in the
      charges. Seventeen described cures involving black magic, in which disease
      supposedly caused by the witch was removed or illness was transferred to another
      individual. Twenty-two included cures by white magic, i.e. herbal remedies and
      non-harmful magical rites. Most cases citing cures by black magic included
      charges of other black magic. However, several trials describing white magical
      cures make no mention of black magic. Most of the accused were probably
      implicated through confessions by other witches. Others may have had psychiatric
      problems and made fantastical statements. Some were antisocial individuals
      reported as witches by neighbours. Few were tried primarily for their healing
      activities.

PMID- 9757506
TI  - Royal College of Physicians of Edinburgh. Consensus Conference on Medical
      Management of Stroke. 26 & 27 May 1998.

PMID- 9757507
TI  - [Personal growth between psychotherapy and pedagogy].
AB  - The relationship between of psychotherapy and education is full of tension. Both
      have similar patterns of action. If one wants to define their relationship, the
      Telos of the respective practice has to be determined. Pedagogy has to be
      concerned with human formation in all its forms of action, and can only be
      executed by each individual him/herself; it is therefore above the principle of
      dialogue. This not only applies to tuition which is linked to personal insight,
      but also to education, which is tied to self-determination.

PMID- 9757508
TI  - [Anxiety of physicians about addiction therapy].
AB  - An analysis of reasons why many physicians show considerable reservations towards
      sufficient diagnostic and treatment measures of alcohol-related disorders
      produced several factors: (a) guilt and aggression are linked to addictive
      disorders in an unproportional way, exceeding the common disease concept; (b)
      defense mechanisms on the part of the physician as well as the patient impair the
      therapeutic relationship. (c) Motivation and treatment of alcoholic patients
      could be improved by offering Balint groups, therapeutic supervision and
      intensified training of physicians.

PMID- 9757509
TI  - [Finding meaning in the final phase of life].
AB  - The last phase of life presents for every human being an enormous challenge. This
      also applies to relatives and those who look after the person concerned. The need
      to give meaning to this consciously lived space of time is made clear when we
      look at the wishes expressed, in more or less the same way, by many seriously and
      terminally ill. In the following article it is tried to highlight this giving of
      meaning by showing the wishes most often expressed and to give examples from
      practical work.

PMID- 9757510
TI  - [Musical dialogue--music therapy in social contact disorder and communication
      difficulties].
AB  - Musical dialogue is a way of leading people incapable of speech out of their
      isolation and difficulty of expression and of helping early emotionally disturbed
      people to get in contact with their feelings. Video excerpts of therapy sessions
      with 3 autistic children show how basic capabilities for interpersonal dialogue
      are made possible through music therapy.

PMID- 9757511
TI  - ["Now tell me, what is your orientation to religion?"--Therapeutic attitude and
      management as an expression of religious faith].
AB  - The essence of the therapeutic process is the relationship: the client
      experiences that the therapist is prepared "to be there" and to remain with
      him/her on the journey unconditionally. A possible goal of personal life, as well
      as of a therapeutic process, is to become oneself. This is described in the
      biblical symbol of Exodus: the motivation of the way and all existential
      experience of being on the way are a possibility to interpret my human existence
      and to fit it into the wider horizon of religious understanding; to know and
      experience a liberator-God (a God who sets me free) as the very basis of my
      development. To what extent therapy--as part of the way the therapist and the
      client go together--always also touches a religious dimension is shown by giving
      examples of some attitudes and consequent actions.

PMID- 9757512
TI  - [Psychiatry and psychotherapeutic medicine].
AB  - Starting from a sketch of the basic view points from which the topic will be
      elucidated, the author focuses on the different logics of psychiatry and
      psychotherapies. The connections between the topic and the somatopsychosocial
      model, the intercorrelation of psycho-genetic interpretative models and
      indication for psychotherapy indicate an approach which is oriented towards the
      disordered person (and not the disorder). This concept is compared with the often
      used definition of psychotherapy by Strotzka. The dependence of the concept on
      traditions in psychiatry (Krafft-Ebing, Jaspers, Kretschmer, E. Bleuler, and M.
      Bleuler) and its consistency with modern multiaxial diagnostic systems (Frances
      et al.) are stressed. Finally the border to psychotherapeutic medicine outside
      psychiatry, both in theory and practice, is stressed.

PMID- 9757513
TI  - [Intuitive dialogue--a way out of emotional blockages with defocusing
      imagination].
AB  - Intuitive dialogues allows to loose trauma-, conflict-, and subject-fixations.
      The defocusing imagery plays an important part role in this method. The
      metaphorical method is oriented on Winnicott, M. Balint, and on Ernesto Grassi
      and on the theory and praxis of modern art-therapy. A specific Balint group in
      the dying scene is described, in which role- and relationship conflicts are
      defocused in form of a mood oriented sensory-metaphorical process. Finally the
      theory and method of the intuitive dialogue is discussed, especially in the
      therapy with tortured patients.

PMID- 9757514
TI  - [Comparative study for assessing quality of life of patients with exogenous sleep
      disorders (temporary sleep onset and sleep interruption disorders) treated with a
      hops-valarian preparation and a benzodiazepine drug].
AB  - This randomized, double-blind, controlled clinical trial in parallel group design
      demonstrated equivalent efficacy and tolerability of a hop-valerian preparation
      compared with a benzodiazepine preparation in patients suffering from sleep
      disorders according to DSM-IV criteria. Sleep quality, fitness and quality of
      life were determined by psychometric tests, psychopathologic scales and sleep
      questionnaires at the beginning of the therapy, end of therapy (duration 2 weeks)
      and then 1 week after cessation of therapy. Patients' state of health (4-point
      scale) and medication tolerability (occurrence of adverse events) were
      documented. Using the following as parameters "Alphabetischer Durchstreichtest,
      Feinmotoriktest, Befindlichkeitsskala, Beschwerdeliste, Schlaffragebogen A and B"
      the differences between beginning and the end of the therapy were analyzed by
      simultaneous testing of the equality or superiority of the test preparation. The
      equivalence of both therapies according to sleep quality, fitness and quality of
      life was proven by a Mann-Whitney-Statistic of 0.50 with a lower boundary of the
      95% confidence interval of 0.46. The patients' state of health improved during
      therapy while showing a deterioration after cessation with both preparations.
      Withdrawal symptoms, however, were documented with benzodiazepine. Only one
      adverse drug reaction was reported during this study, namely stomach complaints
      from both the test and reference medication. This study shows that the
      investigated hop-valerian preparation in the appropriate dose is a sensible
      alternative to benzodiazepine for the treatment of nonchronic and non-psychiatric
      sleep disorders.

PMID- 9757515
TI  - [Urinary incontinence in neurogenic defects and urogenital anomalies in
      childhood].
AB  - Dysraphic defects may cause neurogenic incontinence in childhood. Constipation
      and encopresis are often associated. Depending on the involved segment of the
      spinal cord hyperreflexia or atonia of the detrusor is observed. Similar
      findings, without anatomic correlation, can be seen in occult-neurogenic voiding
      dysfunctions. Therapeutic means aim at preservation of kidney function and the
      best possible continence. If the symptoms cannot be treated by anticholinergic
      drugs in a low-capacity, hypertonic bladder, augmentation by bowel segments or
      continent urinary diversion (e.g. Mainz I pouch) is performed. In the last years
      modalities of clean intermittent self-catheterization in high-capacity, atonic
      bladders could be enhanced by the development of new atraumatic catheter systems.
      Urogenital malformation e.g. proximal epispadias and exstrophic bladder can cause
      incontinence as well. Recently, new therapeutic concepts were introduced. Ectopic
      ureter (extraurethral incontinence) in girls or posterior urethral valves in boys
      as a reason for incontinence must not be forgotten.

PMID- 9757516
TI  - [Incontinence, dementia and multiple morbidity--predictive factors for nursing
      care requirement and nursing home admission].
AB  - The present survey monitored all new admissions to 4 homes for the aged/nursing
      homes in the area of Velbert/Neviges (Nordrhein-Westphalia, Germany) over a 12
      month period in 1996 and 1997, respectively. The study concentrated on the
      importance of incontinence, dementia and comorbidity when predicting need of care
      and removals to nursing homes. The statistical evaluation reveals a net coherence
      between dementia, nursing level and incontinence, and stresses the importance of
      these factors for the nursing home situation in Germany as the position
      increasingly develops into providing for and serving a clientele which is dement
      and heavily in need of care. Furthermore, the evaluation clearly shows that
      incontinence is still taboo to doctors as well as to their patients, and that, in
      spite of the medical and economical importance, the affected and their relatives
      are generally poorly informed. The described results imply a change in how to
      treat incontinence, dementia and comorbidity and should lead to renewed
      therapeutical concepts.

PMID- 9757517
TI  - [Out-patient hospice services--their importance for palliative care in Germany].
AB  - Hospice services can be divided into three groups. Few institutions deliver the
      full scope of palliative home care, most of the others can provide considerably
      less. The third group of services are those that do not support patients but aim
      to establish a home care service or a hospice. In February, 1997 396 home care
      services were working in Germany. 48 of these services provided palliative home
      care, 69 services were hospice initiatives. The scope of services rendered is
      very broad and reaches from psychosocial support to complex medical tasks. In the
      last year, 13,700 patients have been supported at home by hospice services in
      Germany. Palliative care services usually have professional staff, but they would
      not be able to work without honorary help. Beside of support for patients and
      relatives tasks of the home care service are the coordination and exchange
      between in-patient units, general physicians and social care ward. By cooperation
      with all institutions for out-patient and home care as well as with general
      physicians, they contribute to avoid in-patient treatment for their patients.
      Another important function is to spread the hospice idea and work as multipliers
      for knowledges and attitudes in palliative care. The number of home care services
      available in Germany is not sufficient. Only 48 institutions can be ranked as
      palliative care services. The distribution of the hospice services in Germany is
      very irregular, and providers of home care services are even more scarce in the
      eastern part of Germany.

PMID- 9757518
TI  - [Strategies for the application of quality control in intensive care nursing].
AB  - The lack of transparency in nursing duties leads to a reduction in nursing staff,
      particularly among highly trained nurses who have an increased responsibility for
      patient care. A requirement for quality patient care in the future for intensive
      care nurses is to increase transparency of the establishment and evaluation of
      indicators clearly documented in a catalogue of basic and process standards.
      Defining these standards in a framework of necessary and optional care allows for
      cost-benefit-analyses and, on the other hand, departmental reorganisation. This
      catalogue provides the best patient care because it is based on clearly
      established, comprehensive standards and on latest developments in medical and
      nursing research.

PMID- 9757519
TI  - [Strategies for coping with complex problems. Importance of an integrated
      practice to the quality of life in patient care].
AB  - Due to the demographic shift, increasing care needs of elderly and chronically
      ill people have growing impact on the health care services. With complex needs to
      meet, the quality of life of patients depends on multiple factors, of which the
      continuity of care plays an important role. Integrated care requires the exchange
      of information and close coordination on the concept of care between all
      participants in the care process. Yet, collaborative care is often seriously
      jeopardized by lack of knowledge about the concepts, scope of action and requests
      of the involved health professionals and services. Information on the past and
      present health state and on self care resources are prerequisites for adequate
      rehabilitation efforts that are patient-oriented and of high quality. To make
      sure that interventions promote or stabilize the quality of life, the
      participation of the client is inevitable in all stages of the process of care
      planning and coordination. The results of a research project concerning
      cooperative quality improvement carried out at the Agnes Karll Institute for
      Nursing Research stress these assumptions.

PMID- 9757520
TI  - [The future of medical technology assessment in Germany--five proposals for its
      development].
AB  - How progress in medicine will be financed in the future is an important issue
      internationally and in Germany. Medical Technology Assessment is an
      interdisciplinary concept that proposes solutions to this issue. This article
      deals with health political measures which should be taken to implement Medical
      Technology Assessment in the German health care system. Five proposals are
      developed: Establishing a coordinating and communication unit for Medical
      Technology Assessment. Intensifying the research into efficient health care.
      Increasing the use of Medical Technology Assessment in coverage decisions.
      Increasing consumer participation in coverage decisions. Establishing a
      competitive order for the use of expensive technology.

PMID- 9757521
TI  - [Rhinologic aspects in the diagnosis of recurrent epistaxis].
AB  - Severe and frequently occurring epistaxis is a common problem in the praxis of
      the general practitioner. It may be a symptom of another disease which should be
      found. A specific pharmacological history has to be taken. This article tries to
      review the most important rhinologic aspects for the general practitioner that
      the development of the rhinologic disease works as guidance for the differential
      diagnosis of recurrent epistaxis.

PMID- 9757522
TI  - [The antiphospholipid syndrome].
AB  - Antiphospholipid syndrome (APS) is a thrombophilic disorder, which embraces
      almost all specialities. This article includes information about the history,
      classification, epidemiology, clinical manifestations and treatment of the APS.
      It is the aim of this article to introduce the APS with clinical features of all
      medical specialities to show the actuality of the syndrome which is not known
      everywhere.

PMID- 9757524
TI  - [Treatment guidelines--depression. Recommendations for treatment of depression
      from the pharmaceutical commission of the German medical profession].

PMID- 9757523
TI  - [Methodological quality of clinical practice guidelines in Germany: results of a
      systemic assessment of guidelines presented on the Internet].
AB  - Critics claim that most of the German clinical practice guidelines are of poor
      quality having produced by informal ad hoc methodologies without a rigorous
      approach. This paper reports on the systematic appraisal of 329 guidelines
      published online by the Association of the Scientific Medical Societies (AWMF) in
      Germany. The results of this study suggest that most of the guidelines presented
      in Internet do not meet internationally recognised criteria for quality.
      Proposals are offered how to enhance the methodological quality of future
      guidelines.

PMID- 9757525
TI  - [Quality control in Austrian hospitals--results of evaluation].
AB  - The revision of the federal hospital act (Nov. 11, 1993; BGB1 Nr. 801/93) intends
      the introduction of an internal quality control as well as comparisons between
      different hospitals. For the application fo these constitutional requirements,
      the state governments had to develop laws being the basis for the hospital
      management to implement quality assurance. To support the introduction of a
      systematic quality control, the federal ministry of health published a guideline
      for quality assurance which was made available to all hospitals. Now, a
      questionnaire in all Austrian hospitals was designed to evaluate the progress and
      the specific ways of implementations as well as the possible need for action in
      the future.

PMID- 9757526
TI  - [Determinants for diagnostic and therapeutic co-operation between general
      practitioners].
AB  - In the light of new opportunities for structural arrangements in Germany calling
      for higher co-operation between physicians in private practice, determinants for
      diagnostic and therapeutic co-operation need to be examined. In the present
      study, 130 general practitioners were asked in regard to four typical primary
      care indication groups whether they prefer to diagnose and treat the patients on
      their own or in co-operation with colleagues. This self-assessment was validated
      using the data from 2,069 physician-patient contacts: physicians preferring
      therapy in co-operation actually referred patients three times more often.
      Concerning both gastro-intestinal and rheumatic disorders, physicians'
      preferences for diagnostic and therapeutic co-operation are highly correlated
      (phi = 0.491 and 0.528 respectively); preferences for diagnostic and therapeutic
      co-operation across indications are not as strongly correlated (phi = 0.334 and
      0.397 respectively). However, there is no general indication-independent attitude
      towards co-operation for individual physicians: Indication and type of services
      are two factors which--probably in addition to others--affect co-operation
      independently. We confirm earlier conclusions that the detailed analysis of
      provider and patient characteristics together with the actual patient management
      on a case by case basis is a powerful tool for health services research.

PMID- 9757527
TI  - [Regulation of psychotherapists].

PMID- 9757528
TI  - [The Marburg Parent-Child Spelling Trainer--follow up studies after 2 years].
AB  - The results of a two-year parent-child training program are reported. After one
      year of supervised tutoring by one of their parents, the children had only
      improved in those spelling areas that had been worked on in the program,
      otherwise there was no general improvement in their spelling ability. After the
      second year, not only their spelling ability in the specific areas had continued
      to increase, but their general spelling ability (spelling test percentile rank)
      had also improved. Their self-confidence had increased markedly as well.
      Significant predictors of the specific spelling improvement were the specific
      spelling ability at the initial measurement and whether or not the mother was
      working; significant predictors for the general improvement could not be found.
      Supervised tutoring by the parents was shown to be effective for improving
      childrens' spelling ability.

PMID- 9757529
TI  - [An inventory for assessing the quality of life of children and adolescents--a
      pilot study].
AB  - Up to now, the quality of life of children and adolescents with psychiatric
      disorders has rarely been investigated. Not many suitable instruments are
      available. A new one is the "Inventory for the Assessment of the Quality of Live
      in Children and Adolescents" presented here. Objectives and underlying conceptual
      assumptions are discussed, followed by an explanation of the instrument itself
      (questionnaires, rating scales, etc.). Finally, experiences with the application
      of the instrument are reported together with initial empirical results from a
      clinical sample and a sample of high school students. These indicate that the
      instrument usefully assesses clinically relevant information about the quality of
      life of the patients. A broader empirical analysis of this method is being
      prepared.

PMID- 9757530
TI  - [Assessing the quality of life of children and adolescents with psychiatric
      disorders--a review].

PMID- 9757531
TI  - [Disorder-specific psychotherapy in child and adolescent psychiatry].

PMID- 9757533
TI  - [Surgical therapy of the injured spine].

PMID- 9757532
TI  - [How can psychodynamic diagnosis in childhood and adolescence be
      operationalized?].
AB  - Multiaxial diagnostics and classifications in child and adolescent psychiatry
      based on ICD-10 generally now have been operationalized. Initial procedures to
      operationalize psychodynamically oriented concepts are currently underway. One of
      them is the operationalized psychodynamic diagnostics (OPD), which consists of
      five axes: illness concepts and treatment predispositions, human relationships,
      intrapsychic conflict, psychic structure, and the ICD-10. A team is currently
      adapting the adult version of the OPD for use in children and adolescents. Such
      an OPD-CA would affiliate with the MAS, a well-established system of
      classification. Central methodological and conceptual topics of the OPD-CA are
      presented.

PMID- 9757534
TI  - [Reduction and positioning of cervical spine injuries].
AB  - Prerequisites for successful reduction of cervical spine injuries are an exact
      analysis and classification of every lesion. In locked dislocations disc
      protrusion should be excluded prior to reduction by MRI or CT-scan. For manual
      reduction and closed manipulation by the trauma surgeon we use a halo-ring which
      is applied in local anaesthesia and fluoroscopic control. The anatomic position
      is maintained by a halo-fixator until surgery. Skeletal traction is used mainly
      for locked dislocations and late malalignements. Traction is provided by a halo
      ring and weights up to 20 kg. Repeated clinical and neurological examinations are
      necessary to rule out overdistraction of the spine or neurologic deterioration.
      The weight may be reduced after reduction to 2 kg. For intraoperative positioning
      and reduction of cervical spine injuries we designed a special device which is
      connected to the halo ring and allows to fix the head and spine in any desired
      position. It may be used in prone or supine position of the patient. Operative
      reductions are rarely necessary on the cervical spine. Typical indication are
      fractures of posterior elements of the spine preventing closed reduction.
      Reduction manoeuvers depend on the kind of injury and are mainly composed of
      traction and a reversal of the trauma mechanism. The most severe complication is
      a neurologic deterioration. Reports in literature about 13 patients having
      sustained such a fate are showing the following: In most cases disc material
      dislocated in the spinal canal during reduction could be made responsible for the
      catastrophic course. Especially at risk are patients with open reduction from a
      posterior approach.

PMID- 9757535
TI  - [Indications for surgical management of injuries of the cervical spine].
AB  - The indication for operative treatment of serious injuries to the cervical spine
      is basically determinated by instability and dislocation. Timing of the operation
      is based on the neurological deficit. If there is a chance for recovery operative
      treatment is urgent. For the upper cervical spine defined indications are
      existing for type-2-fractures of the dens and C 2/C 3-instabilities of the
      hangman-type with major dislocation. Fractures of C 0 and C 1 are preferably
      treated by conservative methods. Only cases with compound injury patterns with a
      high degree of ligamentous instability may require dorsal fusion. For serious
      injuries of the lower cervical spine operative treatment is needed in most
      instances. Conservative treatment is only indicated if functional stability can
      be proofed and injuries to the discs and compression to the myelon are ruled out.

PMID- 9757536
TI  - [Surgical therapy of dens fracture].
AB  - The use of Anderson/D'Alonso or Aebi/Nazarian classification of dens fractures is
      the basis for exact selection of therapy. The ventral screw-fixation of Anderson
      type-II-Fracture is today the common standard of treatment, especially in the
      elderly. The stabilisation of the fracture with maintenance of atlanto-axial
      rotation-function, the minimal rate of pseudarthrosis compared with conservative
      therapy, the minimal operation trauma and the immediate mobilisation with high
      patient comfort are decisive benefits of this method. Reposition of the fracture,
      visualisation in two planes and the use of adequate instruments are important
      conditions to get optimal operation results. In-vitro-experiments have shown that
      there is no difference of stability in one- or two-screw-technique. Flexion
      injuries with oblique fracture plane, insufficient stability after anterior screw
      fixation and typ-III-fractures are indications for dorsal, atlanto-axial screw
      fixation. The conservative treatment(HALO-vest) is recommended only in otherwise
      inoperable patients.

PMID- 9757537
TI  - [Ventral interbody spondylodesis in injuries of the cervical spine. Indications,
      surgical technique and results].
AB  - Lower cervical spine injuries with instability of the anterior and/or posterior
      column can be treated by anterior interbody fusion and plate fixation. Plates
      available for anterior instrumentation of the lower cervical spine can be divided
      into locking or non-locking systems with uni- or bicortical screw purchase. Our
      biomechanical comparative testing of different screw fixation systems
      demonstrates improved stability with the use of bicortical purchase. Clinical
      studies, however, have proven high fusion rates without loss of correction and a
      low implant related morbidity with the use of unicortical as well of bicortical
      plate systems. Correct reduction and intraoperative positioning of the unstable
      cervical spine is crucial to avoid implant related complications. Also,
      limitations of anterior instrumentation for the treatment of specific lesions of
      the lower cervical spine have to be considered, e.g. in complex lesions with
      axial instability or in fracture dislocations with ankylosing spondylitis.
      Changes or alterations of adjacent segments can be reduced by the use of plates
      with correct lengths, contact of uninjured adjacent discs with implants should be
      avoided. A comparative analysis of two patient collectives--89 patients (1972
      1983) and 102 patients (1987-1994), all of them treated with bicortical plate
      fixation--revealed different results in terms of implant failure, operative
      reduction and loss of correction. All but one surgical fusions had healed
      radiologically. Implant related complications during the first 3 months after the
      initial operation were lower in the latter group, only 3 out of 102 patients (3%)
      with implant loosening versus 7 our of 89 patients (8%) with implant breakage or
      loosening required surgical revision. In all cases technical errors could be
      detected. Clinical follow-ups with personal examination was performed in 144
      patients: 57 of 72 survivors of series I (79%) after an average time of 11 years
      9 months and 87 out of 94 survivors of series II (85%). The radiologic
      examination revealed 2 patients with screw breakage in series I, one patient with
      an asymptomatic implant loosening in series II. Only one case was observed with a
      loss of correction after loosened and early removed hardware. In all other
      patients there was no difference of radiologic angles between postoperative X-ray
      and follow-up. 16 patients, 12 of series I, 4 of series II, were fused in a
      kyphotic position after insufficient preoperative reduction. Radiologic
      alterations of adjacent segments, i.e. spondylophyts or "spontaneous" fusions,
      were observed in more than 50% of all patients of both series. However,
      complaints or persistent pain did not correlate with radiologic findings. Also in
      both series there was a high percentage of patients with mild, residual neck pain
      in spite of a very good radiologic result. Only in a very few cases the
      complaints had to be treated by drugs.

PMID- 9757538
TI  - [Thoraco-lumbar spinal injuries--surgical indications and timing].
AB  - In thoracolumbar spine injuries, the indication for operative treatment and the
      time of operation are defined basically by the injury-pattern and by complicating
      neurological deficits. Immediate decompression is crucial in cases with worsening
      or secondarily occurring neurological involvements; incomplete paraplegia calls
      for undelayed decompression. Since accompanying neurological impairment usually
      represents high-grade instability of the spine, decompression includes fusion of
      the unstable motion segments. Both stability and shape of the spine determine the
      functional and subjective result within certain limits of tolerance. Therefore,
      clear indications for operative treatment exist for the following situations: no
      reduction possible in a closed manner, conservative fixation unpromising after
      closed reduction, restoration of stability uncertain in mainly ligamentous
      injuries. In addition, significant kyphotic and/or scoliotic deformities also
      require operative correction for satisfying results. An individual evaluation of
      both the benefit and the risk of all available therapeutic options is needed for
      every single case of only relative indication for operative measures. The
      accurate analysis of the injury-pattern determining stability and chances of
      healing as well as the knowledge of the efficiency of the planned therapy are
      prerequisites for a differentiated indication.

PMID- 9757539
TI  - [Dorsal stabilization of fractures of the thoracic and lumbar spine by external
      fixator--technique and outcome].
AB  - Posterior stabilization by internal fixator is used as a frequent procedure for
      the surgical treatment of thoracolumbar spine fractures. The technique of
      internal fixator stabilization and its results regarding the correction of spinal
      posture and spinal canal clearance are described. By transpedicular spongiosal
      filling of the reduced vertebral body, a complete consolidation can be achieved.
      Occurring correction losses of the spinal alignment are mainly attributed to the
      collapse of intervertebral segments, thereby suggesting insufficient anterior
      fusion and support after transpedicular intercorporal cancellous bone grafting.
      Spinal canal narrowings can only be cleared partially through posterior approach
      and indirect reduction by internal fixator. In abscence of neurological deficits,
      residual spinal canal encroachments can be tolerated after surgery, since
      remodelling phenomenons occur subsequently. However, symptomatic spinal cord
      compression requires a more efficient decompression technique by direct posterior
      approach, risking manipulation damage of neural structures. The limited
      possibilities of internal fixator technique demand the discerning consideration
      of alternative anterior or combined anterior-posterior procedures for the
      planning of surgical treatment. For spinal fractures with pronounced destruction
      of the anterior column and associated intervertebral disc ruptures, an interbody
      fusion by anterior approach should be performed. In case of additional posterior
      or transverse instability, a supplemental stabilization by internal fixator is
      necessary. For severe spinal canal encroachments at thoracic spine level with
      symptomatic or imminent spinal cord compression, the most efficient decompression
      by an anterior approach is preferred.

PMID- 9757540
TI  - [Laparoscopy-assisted harvesting of free small intestine transplants for
      reconstruction of voice and deglutition after total laryngopharyngectomy--an
      animal experiment study].
AB  - Based on animal trials the presented study results describe a laparoscopic
      assisted removal of an extra-long free jejunal graft to reconstruct voice and
      swallowing after a total laryngo-pharyngectomy in cases with advanced
      malignancies of the larynx including invasion in the upper oesophagus. With a
      microvascular anastomosed small bowel segment, we have been able to reconstruct
      parts of the pharynx and to create a speaking syphon as devised by Ehrenberger in
      an one-stage procedure. The concept of avoidance of an extensive laparotomy may
      result in an decreased morbidity of this surgical procedure. Therefore it
      represents a challenging single indication of minimally invasive surgery of the
      oesophagus. A well established interdisciplinary teamwork is the key for success
      in this extensive procedure.

PMID- 9757541
TI  - [History of surgical instruments: 7. The first electrosurgical instruments:
      galvanic cauterization and electric cutting snare].
AB  - In 1854 the surgeon Albrecht Theodor Middeldorpf (1824-1868) published the first
      monography on the application of electrical current in surgical operations
      ("galvanocautery"). By galvanocautery Middeldorpf defined a procedure in which
      specially constructed parts of surgical instruments (usually thin platinum wires)
      were transformed into glowing heat by means of galvanic current from a zinc
      platinum-battery. In this manner it was possible to perform dissection and
      destruction of tissue as well as coagulation of vessels for hemostasis. His most
      important electrosurgical instruments comprised an electrosurgical knife
      ("galvanocautery") and the electrical cutting snare ("ligatura candens") for
      removal of polypoid tumors. These instruments are the direct ancestors of modern
      electrocautery or cautery snare. The glowing platinum wire was later also applied
      as a light source of cystoscopes. Thus, galvanocautery enabled development of
      endoscopy. Modern diathermy with high-frequent alternating current was introduced
      in medicine by the Dermatologist Franz Nagelschmidt from Berlin.

PMID- 9757542
TI  - [Puncture, catheterization and drainage. 1].

PMID- 9757543
TI  - [Peripheral blood stem cell transplantation as an interdisciplinary challenge-
      theory and practice].
AB  - High dose chemotherapy with consecutive autologous peripheral blood stem cell
      transplantation becomes increasingly important for the treatment of hematological
      diseases and solid tumors. A complete remission or at least a prolonged survival
      can be achieved for numerous malignant diseases by an intensification of chemo-
      and radiotherapy. Therefore, the autologous peripheral blood stem cell
      transplantation (PBSCT) represents an elementary precaution to reduce the therapy
      associated aplasia by administration of hematopoietic precursor cells. Both, high
      dose chemotherapy with consecutive PBSCT demands great clinical experience and
      the collection, processing and positive selection of blood stem cells is a
      challenge for the Transfusion Medicine. Correct handling and utilization of blood
      stem cells for clinical and laboratory purposes (e.g. positive selection) must be
      guaranteed, since each restriction of the function of processed blood stem cells
      may lead to an insufficient engraftment after PBSCT. Therefore, the clinical
      divisions of the University Hospital Munster are planning and practising
      peripheral blood stem cell transplantations in cooperation with the Department of
      Transfusion Medicine. The collection, processing and quality control are
      performed by the Department of Transfusion Medicine in close contact with the
      other clinical departments, who subsequently perform high dose chemotherapy and
      peripheral blood stem cell transplantations.

PMID- 9757544
TI  - [Cervix carcinoma: staging, therapy, after-care. Experiences with magnetic
      resonance tomography of cervix carcinoma based on recent literature 1993 to
      1997].
AB  - The investigation of cervix carcinoma with magnetic resonance tomography (MRT) is
      still controversially discussed with regard to its diagnostic value as well as
      for planning radiation therapy. The purpose of this article is to present and
      discuss papers published between 1993 and 1997 in this field with respect to the
      technique used, the contrast media applied and its clinical value. A literature
      search using three different databases (Medline, Embase, Cancerlit) identified 39
      publications, which were then analysed. Despite the partially suboptimal
      presentation of results in these papers MRT proved superior to other imaging
      modalities. Due to better demarcation of cervix carcinoma with MRT, it was
      possible to calculate tumor value as well as to correctly judge the infiltrative
      character. This allows for a more precise treatment and staging of the patient's
      prognosis. In the future, MRT might be useful in diagnosing recurrence at
      relatively early stage. Unfortunately lymphatic nodes can only be insufficiently
      verified using MRT.

PMID- 9757545
TI  - [Intracytoplasmic injection (ICSI) of cryopreserved testicular spermatozoa (Cryo
      TESE): a retrospective study of the first 250 treatment cycles].
AB  - It is reported on the results of 250 treatment cycles in which we carried out
      intracytoplasmic injections (ICSI) with frozen and thawed testicular spermatozoa
      (cryo-TESE). Up to July 1997 we treated 127 patients, 225 embryo transfers were
      performed (90%), and an average of 2.3 preimplantation embryos were transferred.
      This resulted in 53 clinical pregnancies, six patients aborted (11.3%). The
      pregnancy rate was 21.2% per treatment cycle, 23.5% per embryo transfer, and
      41.7% per patient. This so called cumulative pregnancy rate is still about to
      rise, because 49 out of the 72 non-pregnant patients are still in our ICSI
      program. Twenty-two children are born, 2 twins and 1 triplet. All children are
      healthy and without any major malformations. We conclude from these results that
      using cryopreserved testicular sperm for ICSI is an effective and successful
      approach for the treatment of severe testicular insufficiency. In comparison to
      the use of native testicular sperm with the necessity of repetitive testicular
      biopsies, cryopreservation is advantageous in many concerns (e.g. logistic,
      organisatoric and financial) and is therefore recommended for clinical routine.

PMID- 9757546
TI  - [Endometriosis: clinical, histological and morphometric findings before and after
      Gn-RH agonist therapy].
AB  - After bioptical diagnosis of endometriosis, 81 patients were treated with GnRH
      agonists buserelin or leuprolide for six months. Biopsies before and after
      treatment were used to test a semiquantitative score-system, regarding atrophy of
      glands and stroma cells. Furthermore glandular diameter, circumference and area
      of nuclei were examined morphometrically using a microscopic semiautomatical
      measuring system. Morphometrical and histological alterations during therapy were
      evaluated. Additionally, data suitable for predicting a possible therapeutic
      success were described. After therapy 40 patients still showed endometriotic
      implants (partial responder) in contrast to 41 cases without foci (total
      responder). Therapeutic effect of GnRH-agonists was proved in every respect:
      clinical complaints decreased markedly during GnRH-agonists therapy. Both
      buserelin and leuprolide treated groups revealed increase of atrophy and
      reduction of extension of stroma. Correspondingly morphometrical analysed
      parameters such as diameter, circumference and area of glands decreased during
      therapy as well as area of cytoplasm and nuclei. Except the diameter of glands,
      the leuprolide treated partial responder group (residual foci after GnRH-therapy)
      revealed a stronger therapeutic effect than the buserelin treated partial
      responder group. Obviously this effect seems to be produced by the stronger
      estradiol suppression of leuprolide. Pretherapeutic comparison of measured values
      pointed out a minor distinct endometriosis in the total responder group. Success
      or failure of therapy seems to depend more on the pretherapeutic degree of
      expression of endometriosis. Obviously the kind of applicated GnRH-agonist plays
      a minor distinct role. Morphometrical data of endometriotic foci appear to be
      appropriate to predict a possible therapeutic success of GnRH-agonist therapy.
      But because of many exceptions only a roughly estimated prediction is possible.

PMID- 9757547
TI  - [Morphologic findings in fetuses and placentas of late abortion in the 2nd
      trimester].
AB  - To investigate possible causes of abortion (and intrauterine foetal death) we
      reviewed clinical and morphological data of foetuses and placentas
      morphologically from 830 spontaneous abortions seen during a 12 years period
      (1978-1989) at the Institute of Pathology, University of Leipzig, and the
      Pathological Institute of Hoyerswerda. Our review showed that definite and
      possible causes of foetal death and abortion could be classified as placental,
      foetal maternal, and clinical. Placental changes, which included infection of the
      foetal membranes, disturbances of the uteroplacental circulation (abruptio
      placentae with bleeding) and placental dysmaturity, were the most important
      causes and accounted for 73.8% of the cases. Foetal causes mainly comprised
      multiple twin pregnancies and foetal malformations. In 20 cases (2.4%) we found
      malformations as a cause of foetal death and consecutive abortion. Overall,
      malformations were found in 7.5% of the cases examined. Maternal and obstetric
      complications of pregnancy were less frequent. In 16.5% of our cases, the cause
      of the abortion or intrauterine death remained obscure. However, since 1989,
      genetic analysis and prenatal diagnostic procedures have improved, bringing a
      greater knowledge on the spectrum and aetiology of possible developmental
      disorders in the foetus. This should reduce the number of unexplained abortions.

PMID- 9757548
TI  - [Are there indications for abortion or cesarean section and contraindications for
      spontaneous delivery in ophthalmologic diseases? Case report and overview].
AB  - Management of labor and indications for abortion in patients with ophthalmologic
      diseases are discussed controversially in literature and are often
      overemphasized. We present a case of a pregnant woman with bilateral papilledema
      due to pseudotumor cerebri, because an abortion was in question. This case lead
      us to discuss indications for abortions in patients with pseudotumor cerebri, as
      well as indications for abortions or cesarean sections in patients with high
      myopia, retinal detachment, retinopathy in EPH-gestosis, uveal melanoma and
      diabetic retinopathy. In this article these questions will be discussed.

PMID- 9757549
TI  - [Legal questions in telemedicine].
AB  - Patient data are protected through data protection law and medical
      confidentiality. Telemedicine is a risk factor for medical confidentiality and
      data protection. Therefore there is a need for risk reducing strategies.

PMID- 9757550
TI  - Binding of lactoferrin to bacterial cells of the Clostridium species and their
      agglutination.
AB  - Cell agglutination in cell suspensions of 10 strains of Clostridium by
      lactoferrin (Lf) was observed by obtaining the ratio of increased absorbance
      (RIA) at 450 nm. The RIA values were very different among the species, being
      higher in the cell suspensions with bovine Lf (bLf) than in those with human Lf.
      The binding ability of bLf to the bacterial cells was also observed by an enzyme
      linked ligand-binding assay, using the conjugate of iron-free or iron-saturated
      bLf with horseradish peroxidase (HRPO). The binding ability of bLf was very
      different among the 10 species, and showed a significant correlation with the
      cell agglutination of each strain. bLf formed a complex with the cells of C.
      perfringens, did not dissociate in 2 M NaCl or 4 M urea, but did dissociate in 1
      M KSCN. These results suggest that the agglutination of cells of the Clostridium
      species by bLf is probably caused by the cooperative action of at least
      electrostatic and hydrophobic interactions between bLf and certain components of
      the cell surface.

PMID- 9757551
TI  - Binding characteristics of bovine lactoferrin to the cell surface of Clostridium
      species and identification of the lactoferrin-binding protein.
AB  - The binding characteristics of bovine lactoferrin (bLf) to cells of the
      Clostridium species were observed by using a horseradish peroxidase-bLf
      conjugate. A bLf-binding protein (BP) having a relative molecular mass of about
      33 kDa was confirmed in the surface layer components from 7 strains of the
      Clostridium species. The binding of the conjugate to bLf-BP or C. perfringens was
      strongly blocked by intact Lfs, lysine or arginine residues modified bLf, and
      deglycosylated bLf, but was not by other milk proteins or by the constituent
      sugars of glycan. Bacterial growth was inhibited by bLf, but was slightly
      inhibited by lysine residues modified bLf or deglycosylated bLf. Lactoferricin B
      did not block the binding of the conjugate, but strongly inhibited the bacterial
      growth. This suggests that the lysine or arginine residues and glycan of bLf
      hardly participated in binding bLf to the bacterial cells, but that the amino
      acid residues and glycan played an important role in inhibiting the growth of
      bacteria.

PMID- 9757553
TI  - Novel histamine measurement by HPLC analysis used to assay histidine
      decarboxylase inhibitory activity of shoyuflavones from soy sauce.
AB  - An easy and highly sensitive method for measuring histamine by HPLC analysis
      coupled with precolumn derivatization was established. The amino group of
      histamine was completely colorimetrically labelled with 4-N,N-dimethylamino
      azobenzene-4'-isothiocyanate (DABITC) in the presence of sodium bicarbonate at 90
      degrees C for 5 min. The derivative was sensitively and easily analyzed by HPLC
      on a Cosmosil 5SL column using CHCl3/N,N-dimethylformamide/H2O (210:90:4)
      containing 0.4% acetic acid. Using the established method, histidine
      decarboxylase (HDC) inhibitory activities of three tartaric acid isoflavone
      derivatives, named shoyuflavones, isolated from soy sauce were examined in vitro
      by measuring the histamine produced by HDC. They showed intense inhibition of the
      activities of HDC from both mouse mastocytoma P-815 cells and Clostridium
      perfringens.

PMID- 9757552
TI  - Proanthocyanidins from barley bran potentiate retinoic acid-induced granulocytic
      and sodium butyrate-induced monocytic differentiation of HL60 cells.
AB  - Polyphenol extract from barley bran (BPE) induced nitro blue tetrazolium (NBT)
      reducing activity and alpha-naphthyl butyrate esterase activity in HL60 human
      myeloid leukemia cells. Because BPE induced the biochemical markers of HL60 cell
      differentiation, we investigated the effects of proanthocyanidins isolated from
      BPE on the HL60 cell differentiation of HL60 cells. Prodelphinidin B-3, T1, T2,
      and T3 induced 26-40% NBT-positive cells and 22-32% alpha-naphthyl butyrate
      esterase-positive cells. Proanthocyanidins potentiated retinoic acid (all-trans
      retinoic acid)-induced granulocytic and sodium butyrate-induced monocytic
      differentiation in HL60 cells.

PMID- 9757554
TI  - Structure-function relationship of T-2 toxin and its metabolites in inducing
      thymic apoptosis in vivo in mice.
AB  - Recently we found that a single administration of T-2 toxin (T-2), a
      trichothecene mycotoxin, into mice induced DNA fragmentation, a biochemical
      hallmark of apoptosis, in the thymus. In this study, we investigated the
      effective chemical structure(s) of T-2-derived metabolites capable of inducing
      thymic apoptosis in vivo in mice. Metabolic conversion of T-2 to 3'-hydroxy-T-2
      toxin (3'-OH-T-2) did not diminish the apoptosis-inducing activity, since
      essentially the same level of fragmented DNA was detected in the thymus taken
      from mice injected with either T-2 or 3'-OH-T-2. In contrast, hydrolysis of T-2
      and 3'-OH-T-2 at the carbon-4 (C-4) position to HT-2 toxin (HT-2) and 3'-hydroxy
      HT-2 toxin (3'-OH-HT-2), respectively, greatly decreased the level of DNA
      fragmentation. Similarly, hydrolysis of T-2 at the carbon-8 (C-8) position to
      neosolaniol strongly diminished its ability to induce DNA fragmentation. T-2
      tetraol, having no ester groups, was unable to induce apoptosis. Based on the
      data presented in this study, we concluded that both the acetyl group at the C-4
      position and the isovaleryl or 3'-hydroxyisovaleryl group at the C-8 position of
      the T-2 molecule are important for inducing cell death through apoptosis in the
      thymus.

PMID- 9757555
TI  - Lipoxygenase-1 from soybean seed inhibiting the activity of pancreatic lipase.
AB  - There are some similar characteristics in protein nature between the lipase
      inhibitor from soybean seed and soybean lipoxygenase-1 (LOX-1). Thus, the
      inhibiting protein for pancreatic lipase was prepared from defatted soybean meal
      by the procedure for the isolation of LOX-1 [Axelrod et al., Methods in
      Enzymology, 71, 441-451 (1981)]. The LOX-1 from soybean seed dose-dependently
      inhibited the release of fatty acid from a soybean oil emulsion, and the
      concentration of LOX-1 to cause half inhibition of the lipase activity was 3.2 x
      10(-7) M. The LOX-1 obtained from E. coli transfected with a plasmid carrying the
      soybean LOX-1 gene also inhibited the lipase activity. However, the lipase
      inhibiting activity by the LOX-1 was not affected by the presence of
      nordihydroguaiaretic acid, an inhibitor for LOX, in the reaction mixture. These
      results show that the soybean LOX-1 inhibits lipase activity regardless of its
      lipoxygenase activity.

PMID- 9757556
TI  - Effect of indigestible oligosaccharides on the hepatotoxic action of D
      galactosamine in rats.
AB  - The effects of dietary oligosaccharides on the hepatotoxic action of D
      galactosamine (GalN) were investigated in this study. Male Wistar rats fed with
      20% casein diets containing 10% oligosaccharide or D-galactose (Gal) for 2 weeks
      were injected with GalN (1,900 mg/kg of body weight), and the plasma aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT) activities and the
      hepatic glycogen concentration were examined 20 hours after the injection. The
      plasma AST and ALT activities in experiment 1 for the Gal + neomycin (NEO) group
      were significantly lower than those for the control (C), NEO, raffinose (RAF) +
      NEO and galacto-oligosaccharide (GA-LO) + NEO groups. In experiment 2, these
      activities were significantly lower in the Gal, Gal + NEO and RAF groups than in
      the RAF + NEO group when the groups were treated with GalN. On the other hand, in
      respect of the hepatic glycogen concentration in experiment 1, that of the Gal +
      NEO group was higher than that of the C, NEO, RAF + NEO or GALO + NEO groups. In
      experiment 2, this parameter was significantly higher in the Gal, Gal + NEO and
      RAF groups than in the RAF + NEO group after the GalN treatment. As a result, it
      is suggested that the GalN-hepatitis-suppressive effects of indigestible
      oligosaccharides such as RAF or GALO is mediated by the action of intestinal
      bacteria.

PMID- 9757557
TI  - Construction of a BAC library of the rice blast fungus Magnaporthe grisea and
      finding specific genome regions in which its transposons tend to cluster.
AB  - We have constructed a BAC library of the rice blast fungus Magnaporthe grisea
      consisting of 5760 clones. The insert size ranged from 35 to 175 kbp, with an
      average of 120 kbp. The library is about 18 genomes equivalent, therefore
      covering more than 99.999% of the genome. This library is the first to be
      constructed using a rice pathogenic wild type isolate. Improved high molecular
      weight DNA size fractionating helped to construct the library with high
      efficiency. Total library clones were arranged onto two nylon membranes for
      efficient screening. Test hybridization with a single-copy RFLP marker showed ten
      positive clones, of which restriction patterns indicated no chimerality or
      deletions. As a model case of application of this library, the distribution of
      the well-studied fungal retrotransposons MGSR1, MGR583, and MAGGY and DNA
      transposons MGR586 and Pot2 was analyzed. Of all the BAC clones, 10%, 13%, 18%,
      12%, and 23% contained MGSR1, MGR583, MAGGY, MGR586 and Pot2, respectively. The
      percentage of clones possessing more than five kinds of transposons was 1.4%, 215
      times greater than the expected number. The results show that these transposons
      were distributed in clusters in the M. grisea genome.

PMID- 9757558
TI  - Production of a mixture of antimicrobial organic acids from lactose by co-culture
      of Bifidobacterium longum and Propionibacterium freudenreichii.
AB  - The antimicrobial activities of standard solutions of three organic acids
      (lactic, acetic, and propionic acids) were compared using Micrococcus luteus,
      Pseudomonas sp. and Staphylococcus aureus as test microorganisms. At the same
      concentrations of the undissociated form, the antimicrobial activities of acetic
      and propionic acids were higher than that of lactic acid, irrespective of test
      microorganisms. In a single cultivation of Bifidobacterium longum, a mixture of
      lactic (17 g/l) and acetic (20 g/l) acids was produced from 50 g/l lactose and
      its antimicrobial activities against M. luteus, Pseudomonas sp., and S. aureus
      correspond to that of 32, 19, and 25 g/l of acetic acid, respectively. To
      increase the total antimicrobial activity, a co-culture of B. longum and
      Propionibacterium freudenreichii, in which lactic acid produced once from lactose
      by B. longum was converted to acetic and propionic acids by P. freudenreichii,
      was done using TPY medium containing commercially available peptones as a
      nitrogen source. By the sequential conversion of lactose using the two
      microorganisms, the culture supernatant containing a mixture of acetic (27 g/l)
      and propionic (13 g/l) acids without lactic acid was produced. The antimicrobial
      activities of the mixture against M. luteus, Pseudomonas sp., and S. aureus were
      35, 30, and 26 g/l as a concentration of acetic acid, respectively, higher than
      that obtained in the cultivation of B. longum alone. When the medium containing
      an enzymatic hydrolyzate of whey proteins with a protease was used in the co
      culture of B. longum and P. freudenreichii, the culture supernatant containing
      the mixture of organic acids was also obtained in the same manner as the co
      culture using TPY medium and the activities were 43, 29, and 29 g/l as a
      concentration of acetic acid for M. luteus, Pseudomonas sp. and S. aureus,
      respectively.

PMID- 9757559
TI  - Purification and characterization of recombinant human granulocyte colony
      stimulating factor (rhG-CSF) derivatives: KW-2228 and other derivatives.
AB  - Various derivatives of recombinant human granulocyte colony-stimulating factor
      (rhG-CSF) have been overproduced in Escherichia coli with the strong, inducible
      trp promoter. A derivative designated as KW-2228 in which the amino acids were
      replaced at five positions showed more potent granulopoietic activity and
      stability than those of wild-type both in vitro and in vivo. The purification
      involved a sequential renaturation process and three-step chromatography.
      Refolding succeeded in very high yield using a urea system. The purity of KW-2228
      was greater than 99% as measured by SDS-PAGE and HPLC analysis. According to
      circular dichroism and nuclear magnetic resonance spectroscopy, rhG-CSF and KW
      2228 have very similar conformations. This suggests that the substitution of five
      amino acids does not appreciably change the conformation of hG-CSF. KW-2228
      ([Ala1, Thr3, Tyr4, Arg5, and Ser17]-hG-CSF) and derivative A ([Ala1, Thr3, Tyr4,
      Arg5]-hG-CSF) are easily crystallized and they show similar in vitro activity. On
      the other hand, neither rhG-CSF nor derivative B ([Ser17]-hG-CSF) are
      crystallized under the same conditions. Thus, the four amino acid substitution
      (Ala1, Thr3, Tyr4, Arg5) of the N-terminal sequence may facilitate
      crystallization. The change of Cys17 to Ser may not influence the stability and
      activity of hG-CSF.

PMID- 9757560
TI  - Effects of polyphenol substances derived from Theobroma cacao on gastric mucosal
      lesion induced by ethanol.
AB  - The antiulcer activity of cacao liquor water-soluble crude polyphenols (CWSP) was
      examined. CWSP, alpha-tocopherol, sucralfate (500 mg/kg), and cimetidine (250
      mg/kg) were orally administered to male SD rats 30 minutes before ethanol
      treatment. 5 ml/kg of ethanol given intragastrically caused lesions in mucosa of
      the glandular stomach. CWSP caused a reduction of such hemorrhagic lesions as
      well as cimetidine and sucralfate which are typical antiulcer drugs, but alpha
      tocopherol was less effective. Thiobarbituric acid reactive substances in gastric
      mucosa significantly increased with ethanol administration. CWSP treatment
      significantly reduced this change. The administration of ethanol extensively
      increased myeloperoxidase (MPO) but not xanthine oxidase (XOD) activity. CWSP
      reduced the activities of both enzymes; they were considered the main sources of
      oxygen radicals. According to an in vitro study, CWSP directly reducted XOD but
      not MPO. These results suggest that the antiulcer mechanism of CWSP was not only
      radical scavenging but also modulation of leukocyte function.

PMID- 9757561
TI  - Thermostable beta-galactosidase from an extreme thermophile, Thermus sp. A4:
      enzyme purification and characterization, and gene cloning and sequencing.
AB  - We purified and characterized a thermophilic beta-galactosidase from Thermus sp.
      A4 isolated from the Atagawa hot spring (Shizuoka, Japan). The enzyme was
      monomeric, and its molecular mass was estimated to be 75 kDa by SDS
      polyacrylamide gel electrophoresis. The enzyme was extremely thermostable and
      retained its full activity after incubation at 70 degrees C for 20 h. The Km
      observed were 5.9 mM for ortho-nitrophenyl beta-D-galactopyranoside and 19 mM for
      lactose. We cloned and analyzed the complete sequence of the gene encoding this
      enzyme. It was found to consist of 645 amino acid residues. We propose that this
      enzyme and seven other unclassified beta-galactosidases are new members of family
      42 of the glycosyl hydrolases.

PMID- 9757562
TI  - Molecular properties and activity of a carboxyl-terminal truncated form of
      xylanase 3 from Aeromonas caviae W-61.
AB  - Aeromonas caviae W-61 produces five species of xylanases, xylanases 1, 2, 3, 4,
      and 5 [Nguyen, V.D. et al., Biosci. Biotechnol. Biochem., 56, 1708-1712 (1993)
      and Appl. Environ. Microbiol., 57, 445-449 (1991)]. While preserving a purified
      xylanase 3 preparation from A. caviae in solution at 4 degrees C, the xylanase 3
      was found to be proteolyzed to give a truncated form with a smaller molecular
      mass than that of the intact one. It appears likely that the truncated form of
      xylanase 3 was produced in this particular purification experiment by the action
      of a contaminating protease. We isolated the truncated form of xylanase 3
      (Xyn3tr), of which the C-terminal 102-residue segment is missing. By the chemical
      analysis of the N- and C-terminal amino acid residues of Xyn3tr and the DNA
      sequencing analysis of the xylanase 3 gene (xyn3), the N-terminal 398th proline
      residue of xylanase 3 was found to be the C-terminus of Xyn3tr. Xyn3tr had the
      activity to form xylotriose (X3), xylotetraose (X4), xylopentaose (X5), and
      xylohexaose (X6) as main final products from oat spelt xylan. In contrast, intact
      xylanase 3 released X6 and higher xylo-oligosaccharides as main products.
      Xylanase 3 hydrolysed X4 through X6. However, Xyn3tr had no activity towards X4
      and X5. The recombinant Xyn3tr and recombinant xylanase 3 (XYN3) were purified
      homogeneously from the periplasmic space of E. coli harboring the plasmids pXYN3
      and pXYN3tr, which include xyn3 and xyn3tr genes, respectively, and their
      enzymatic activities were measured. The cleavage patterns of oat spelt and xylo
      oligosaccharides by XYN3tr were identical with that by intact Xyn3tr. Thus, we
      conclude that the C-terminal region comprising a 102-residue segment in xylanase
      3 is involved in governing the molecular size of xylo-oligosaccharides cleaved
      from beta-1,4-xylan by the enzyme and in the hydrolytic activity towards X4 and
      X5.

PMID- 9757563
TI  - Synthesis and biological activities of (-)-6-n-octyl-indolactam-V, a new potent
      analogue of the tumor promoter (-)-indolactam-V.
AB  - (-)-Indolactam-V (1) without a hydrophobic chain at positions 6 and 7 of the
      indole ring is a weak tumor promoter compared with teleocidin Bs. To investigate
      the effects of the hydrophobic substituent at position 6 of teleocidin Bs, we
      synthesized (-)-6-n-octyl-indolactam-V (2) by a palladium-catalyzed coupling
      reaction from (-)-6-bromo-indolactam-V (7) which had been obtained by microbial
      conversion with Streptoverticillium blastmyceticum NA34-17 as the key step. (-)-7
      n-Octyl-indolactam-V (3) with potent biological activities comparable to those of
      teleocidin Bs was similarly synthesized from (-)-7-bromo-indolactam-V as a
      positive control. Compound 2 showed similar biological activities to those of 3,
      indicating that the effect of the hydrophobic substituent at position 6 of 1 was
      identical to that at position 7.

PMID- 9757564
TI  - Characterization of a mutant of Lactococcus lactis with reduced membrane-bound
      ATPase activity under acidic conditions.
AB  - A mutant of Lactococcus lactis subsp. lactis C2 with reduced membrane-bound
      ATPase activity was characterized to clarify its acid sensitivity. The
      cytoplasmic pH of the mutant was measured in reference to the parental strain
      under various pH conditions. At low pH, the mutant could not maintain its
      cytoplasmic pH near neutral, and lost its viability faster than the parental
      strain. The ATPase activities of cells cultured under neutral and acidic
      conditions using pH-controlled jar fermentors were measured. The relative ATPase
      activity of the mutant at pH 7.0 was 42% of the parental strain. At pH 4.5, the
      parental strain showed an ATPase activity 2.8-fold higher than that at pH 7.0
      while the level of increase in the mutant was only 1.6. Northern and Western blot
      analyses found that at pH 7.0 the transcriptional level and the amount of F1 beta
      subunit were similar in both strains, suggesting that the mutant has a defective
      ATPase structural gene. On the other hand, at pH 4.5 the transcriptional level
      and the amount of F1 beta subunit were found to be significantly higher in both
      strains than those at pH 7.0. From these results, it was suggested that the
      mutant has a normal regulation system for ATPase gene expression. It was
      concluded that the mutant is acid sensitive due to its inability to extrude
      protons out of the cell with defective ATPase under acidic conditions.

PMID- 9757565
TI  - Changes in the level of sialic acid in plasma, brain and liver of inherently
      scorbutic rats during vitamin C and E deficiencies.
AB  - The plasma level of sialic acid (NeuAc) in inherently scorbutic [Osteogenic
      Disorder Shionogi (ODS)] rats was increased by 21 days of vitamin C deficiency.
      The brain content of NeuAc was decreased by deficiencies of these vitamins. The
      NeuAc level in the liver was not affected significantly by these deficiencies.

PMID- 9757566
TI  - Use of Escherichia coli polyphosphate kinase for oligosaccharide synthesis.
AB  - The Escherichia coli polyphosphate kinase (PPK) has been known to catalyze the
      reversible transfer of phosphate molecules between ATP and polyphosphate
      (poly(P)). It has also been found that the PPK catalyzes the kination of not only
      ADP but also other nucleoside diphosphates (NDPs) using poly(P) as a phosphate
      donor, yielding nucleotide triphosphates (NTPs). We used the PPK and poly(P) in
      place of pyruvate kinase and phosphoenol pyruvate for NTP regeneration followed
      by synthesis of sugar nucleotides in a cyclic synthesis system for
      oligosaccharides. It was confirmed that the PPK efficiently catalyzed the UTP
      regeneration in the cyclic system of N-acetyllactosamine synthesis. This novel
      activity of PPK enables us to perform the practical synthesis of
      oligosaccharides.

PMID- 9757567
TI  - Whole sequence of spoIIIE-like, sporulation-inhibitory, and transfer gene (spi)
      in a conjugative plasmid, pSA1.1, of Streptomyces azureus and detection of spi
      like gene in the actinomycete chromosome.
AB  - The nucleotide sequence of spoIIIE-like and the sporulation-inhibitory and
      transfer gene (spi) in a conjugative plasmid, pSA1.1, of Streptomyces azureus
      were examined to detect the promoter region. Using Southern blotting and a spi
      fragment as probe, spi-like genes were detected in chromosomes of the host and
      other actinomycetes. These results suggest that there is a spi- and spoIIIE-like
      gene in chromosomes of some actinomycetes.

PMID- 9757568
TI  - Characterization of ribonucleases from culture medium of Lentinus edodes.
AB  - Lentinus edodes (shiitake) cultivated in potato dextrose medium produced five
      RNases in the culture filtrate. The two major RNases (RNase Le37 and RNase Le45)
      were highly purified and their molecular masses, base specificities, N-terminal
      amino acid sequences, and amino acid compositions were analyzed and compared to
      RNase Le2 isolated from the fruit bodies of the same mushroom. RNase Le37 and
      RNase Le45 are base non-specific and adenylic acid preferential RNases like RNase
      Le2 and their N-terminal sequences are very similar to RNase Le2, but they are
      glycoproteins and their amino acid compositions are significantly different from
      that of RNase Le2. In addition to these enzymes, a guanylic acid-specific RNase
      with a molecular mass 13 kDa was partially purified. Since RNase Le2, which has
      very similar N-terminal sequence to RNase Le37 and RNase Le45, was not excreted
      from the mycelia, the analysis of the structures of these two excreted RNase may
      shade a light on the mechanism of excretion of RNases in this organism.

PMID- 9757570
TI  - Expression of Aspergillus aculeatus No. F-50 cellobiohydrolase I (cbhI) and beta
      glucosidase 1 (bgl1) genes by Saccharomyces cerevisiae.
AB  - A cellobiohydrolase I (cbhI) and a beta-glucosidase 1 (bgl1) gene of Aspergillus
      aculeatus were expressed in Saccharomyces cerevisiae. The transformed cells
      secreted the enzymes efficiently in an active form. The recombinant CBHI gave two
      bands of different molecular mass (110 and 90 kDa) and the recombinant BGL1 gave
      one band (180 kDa) by SDS-PAGE. The recombinant CBHI and BGL1 had the same
      enzymatical properties as the native enzyme except for the specific activity
      toward cellulosic substrates. By the combination of three different types of
      cellulases, FI-CMCase, CBHI, and BGL1, we could hydrolyze Avicel up to 59% under
      our experimental conditions.

PMID- 9757569
TI  - Effects of glycosylation of the residue at position 14 in ovine angiotensinogen
      on the human renin reaction.
AB  - A mutant angiotensinogen, S14N, in which Ser14 of ovine angiotensinogen was
      replaced by Asn to form a N-glycosylation site, was produced in CHO cells. The
      molecular weight was about 3,000 larger than that of wild-type ovine
      angiotensinogen, indicating that S14N angiotensinogen was glycosylated at Asn14.
      In the reaction with human renin, the km of mutant angiotensinogen was 3 times
      increased, but the Vmax was not affected by the mutation.

PMID- 9757571
TI  - Biological and structural properties of cyclic peptides derived from the alpha
      amylase inhibitor tendamistat.
AB  - Six cyclic peptides with 5, 7, 9, 11, 13, and 15 amino acids, with the inhibitory
      sequence of the alpha-amylase inhibitor tendamistat, were synthesized. The 11
      residue peptide inhibited porcine pancreatic alpha-amylase most potently (K1 0.29
      +/- 0.09 microM). For the 11-residue peptide, the circular dichroism study
      suggested a preliminary relationship between its inhibitory activity and
      structural property.

PMID- 9757572
TI  - Phospholipid deacylating activities included in yeast.
AB  - Yeast had been known to contain only one kind of phospholipid deacylating enzyme
      with an optimal pH in the acidic range. However, among 8 genera and 25 strains, 7
      genera and 13 strains had phospholipid deacylating activity at pH 8.0, when
      screening of enzyme activity was done with micellar and liposomal substrates. The
      enzymatic properties of phospholipid deacylating enzyme existing in yeast was not
      related to genetic identity based on 18S rRNA gene sequence. The results suggest
      that yeast contains enzymes showing a variety of properties depending on the
      species of yeast, and further studies on this enzyme with more varieties of
      yeasts are necessary for understanding the physiological roles of the enzyme in
      yeast.

PMID- 9757573
TI  - Nucleotide sequence of the gene encoding the precursor protein of pepstatin
      insensitive acid protease B, scytalidopepsin B, from Scytalidium lignicolum.
AB  - A chromosomal DNA of Scytalidium lignicolum was digested with Sau3AI. The digest
      was self-ligated and amplified by inverse PCR procedure using primers designed
      based on the nucleotide sequences of up- and down-stream regions of an intron
      present in the scytalidopepsin B gene. Analysis of the nucleotide sequence of PCR
      product (700 bp) showed that the enzyme is synthesized as a precursor protein
      consisting of the prepro- and mature enzyme regions. The deduced amino acid
      sequence was highly similar to those of aspergillopepsin A and recently reported
      endothiapepsins B and C, but quite different from those of pepstatin-insensitive
      bacterial acid proteases and the pepstatin-sensitive aspartic protease family.

PMID- 9757574
TI  - Mapping of human DNA-binding nuclear protein (NP220) to chromosome band 2p13.1
      p13.2 and its relation to matrin 3.
AB  - Human NP220 (hNP220) is a novel DNA-binding nuclear protein, which has an
      arginine/serine-rich motif and polypyrimidine tract-binding motif, and NP220s and
      matrin 3 are thought to form a novel family of nuclear proteins. We have
      determined a chromosomal localization of the cDNA encoding human NP220 to 2p13.1
      p13.2 by using fluorescence in situ hybridization. Human matrin 3 cDNA was mapped
      to chromosomes 1p13.1-p21.1 and 5q31.3, demonstrating that these novel nuclear
      proteins with similar functions are on different chromosomes.

PMID- 9757575
TI  - Evaluation of the macrocyclic antibiotic avoparcin as a new chiral selector for
      HPLC.
AB  - Avoparcin is a macrocyclic glycopeptide antibiotic structurally related to
      vancomycin, teicoplanin, and ristocetin A. When attached to 5-microns spherical
      silica gel, the avoparcin proved to be an effective chiral stationary phase (CSP)
      that could be used in the reversed-phase, normal-phase, and polar-organic modes.
      The avoparcin CSP was complimentary to the other macrocyclic glycopeptide CSPs in
      that it could resolve some racemates that the others could not, and vice versa.
      Some important compounds resolved on the avoparcin CSP include verapamil,
      thyroxine, mephenytoin, and 2-imidazolidone-4-carboxylic acid. The use of this
      CSP and the optimization of separations on it are discussed. Avoparcin appears to
      be a useful addition to this family of CSPs.

PMID- 9757576
TI  - Near-UV, circular dichroism, and fluorescence spectra of a rigid rodlike helical
      polysilane bearing trietheral moiety in ethanol/water.
AB  - An optically active, rigid rodlike helical polysilane with 6, 9, 12
      trioxatetradecyl and (S)-2-methylbutyl substituents (1) was newly obtained as a
      very high molecular weight polymer of several million. Due to the presence of
      trietheral substituent, 1 was readily soluble in a polar solvent such as ethanol
      and a mixture of ethanol and water, but was insoluble in pure water. Polysilane 1
      in pure ethanol at room temperature exhibited an intense and narrow ultraviolet
      (UV) and circular dichroism (CD) absorptions at 323 nm, associated with an almost
      mirror imaged fluorescence (FL) at 328 nm, that are characteristics of rigid
      rodlike, single-screw-sense helical polysilanes reported previously. When
      solution temperature was changed from 60 degrees C to -104 degrees C, a global
      shape of 1 expanded associated with an increase of segment length, whereas a
      screw pitch tended to be wound tightly. On the other hand, as a solvent polarity
      became poor, a global shape of 1 shrunk associated with an decrease of segment
      length and formed a chiral motif with an M-helicity between two helical segments
      with a kink. At a ratio of 50% of ethanol/water of 50:50 (v/v), 1 became
      insoluble and formed aggregates.

PMID- 9757577
TI  - On the effects of noncontingent delivery of differing magnitudes of
      reinforcement.
AB  - We conducted a parametric analysis of response suppression associated with
      different magnitudes of noncontingent reinforcement (NCR). Participants were 5
      adults with severe or profound mental retardation who engaged in a manual
      response that was reinforced on variable-ratio schedules during baseline.
      Participants were then exposed to NCR via multielement and reversal designs. The
      fixed-time schedules were kept constant while the magnitude of the reinforcing
      stimulus was varied across three levels (low, medium, and high). Results showed
      that high-magnitude NCR schedules produced large and consistent reductions in
      response rates, medium-magnitude schedules produced less consistent and smaller
      reductions, and low-magnitude schedules produced little or no effect on
      responding. These results suggest that (a) NCR affects responding by altering an
      establishing operation (i.e., attenuating a deprivation state) rather than
      through extinction, and (b) magnitude of reinforcement is an important variable
      in determining the effectiveness of NCR.

PMID- 9757578
TI  - Teaching multiplication facts to students with learning disabilities.
AB  - Multiple baseline designs were used to examine the effects of an instructional
      package on accuracy of performance in solving multiplication facts by 3 students
      with learning disabilities. The instructional package included the following
      components: (a) a modified instructional sequence in which multiplication facts
      were grouped into the zeros, ones, doubles, fives, and nines categories, and
      those remaining; (b) identification of the category in which each fact belonged;
      (c) mnemonic strategies associated with solving facts in each category; and (d)
      steps to be completed for solving facts in each category. Results indicated that
      the instructional package produced substantial and immediate effects. After
      receiving instruction, a participant's accuracy was often 100%, and this was
      maintained throughout the evaluation even as other strategies were introduced.
      Comparable results occurred across students, demonstrating replication of the
      effects of the instructional package.

PMID- 9757579
TI  - Functional analysis and treatment of destructive behavior maintained by
      termination of "don't" (and symmetrical "do") requests.
AB  - We used descriptive assessment information to generate hypotheses regarding the
      function of destructive behavior for 2 individuals who displayed near-zero rates
      of problem behavior during an experimental functional analysis using methods
      similar to Iwata, Dorsey, Slifer, Bauman, and Richman (1982/1994). The
      descriptive data suggested that destructive behavior occurred primarily when
      caregivers issued requests to the participants that interfered with ongoing high
      probability (and presumably highly preferred) behaviors (i.e., a "don't" or a
      symmetrical "do" request). Subsequent experimental analyses showed that
      destructive behavior was maintained by contingent termination of "don't" and
      symmetrical "do" requests but not by termination of topographically similar "do"
      requests. These results suggested that destructive behavior may have been
      maintained by positive reinforcement (i.e., termination of the "don't" request
      allowed the individual to return to a highly preferred activity). Finally, a
      treatment (functional communication training plus extinction) developed on the
      basis of these analyses reduced destructive behavior to near-zero levels.

PMID- 9757580
TI  - Effects of differential reinforcement on the generalization of a replacement mand
      in three children with severe language delays.
AB  - We investigated variables that may influence the generalization of a replacement
      mand in 3 young children with severe language delays. A multiple baseline design
      consisting of one stimulus class of manding opportunities that we arbitrarily
      divided into three categories (i.e., food, toys, and events) was used for each
      child. During baseline probes, all children manded mainly by reaching, grabbing,
      or leading. We then taught each child a replacement mand using a single member of
      the stimulus class. Acquisition of the replacement mand occurred under highly
      restricted conditions in a setting that was completely isolated from the
      generalization settings. Postacquisition probes revealed almost exclusive use of
      old manding forms. Subsequently, extinction of the old forms and reinforcement of
      the replacement mand were introduced in a sequential fashion. Two children
      manifested a substantial increase, and 1 child displayed a moderate increase in
      the occurrence of the replacement mand (i.e., generalization occurred). These
      results suggest that a differential reinforcement procedure can alter the
      probability of the occurrence of response class members across a variety of
      stimulus conditions.

PMID- 9757581
TI  - Utilizing increased response effort to reduce chronic hand mouthing.
AB  - The effects of increased response effort on levels of hand mouthing, leisure
      engagement, and adaptive elbow flexion were investigated with 2 individuals who
      had been diagnosed with profound disabilities. Arm restraints designed to alter
      the amount of physical effort necessary to engage in hand mouthing were used.
      Results indicated that the treatment strategy reduced levels of hand mouthing but
      produced only small to moderate reductions in levels of leisure engagement and
      adaptive elbow flexion. At follow-up, the effects of increased response effort on
      hand mouthing and leisure engagement were maintained for both participants;
      however, the restraints were associated with substantial reductions in adaptive
      elbow flexion for 1 participant.

PMID- 9757582
TI  - Teaching elementary students with developmental disabilities to recruit teacher
      attention in a general education classroom: effects on teacher praise and
      academic productivity.
AB  - Four fourth graders with developmental disabilities were trained to recruit
      teacher attention while they worked on spelling assignments in a general
      education classroom. The students were taught to show their work to the teacher
      two to three times per session and to make statements such as, "How am I doing?"
      or "Look, I'm all finished!" Training was conducted in the special education
      classroom and consisted of modeling, role playing, error correction, and praise.
      A multiple baseline across students design showed that recruitment training
      increased (a) the frequency of students' recruiting, (b) the frequency of teacher
      praise received by the students, (c) the percentage of worksheet items completed,
      and (d) the accuracy with which the students completed the spelling assignments.

PMID- 9757584
TI  - Brief functional analysis and treatment of a vocal tic.
AB  - This study sought to extend functional methodology to the assessment and
      treatment of habits. After a descriptive assessment indicated that coughing
      occurred while eating, a brief functional analysis suggested that social
      attention was the maintaining variable. Results demonstrated that treatment,
      derived from the assessment and analysis data, rapidly eliminated the cough. We
      discuss the appropriateness of using functional analysis procedures for deriving
      treatments for habits in a clinical setting.

PMID- 9757583
TI  - Applying behavior analysis to clinical problems: review and analysis of habit
      reversal.
AB  - This article provides a review and analysis of habit reversal, a multicomponent
      procedure developed by Azrin and Nunn (1973, 1974) for the treatment of nervous
      habits, tics, and stuttering. The article starts with a discussion of the
      behaviors treated with habit reversal, behavioral covariation among habits, and
      functional analysis and assessment of habits. Research on habit reversal and
      simplified versions of the procedure is then described. Next the article
      discusses the limitations of habit reversal and the evidence for its generality.
      The article concludes with an analysis of the behavioral processes involved in
      habit reversal and suggestions for future research.

PMID- 9757585
TI  - Functional analysis and extinction of different behavior problems exhibited by
      the same individual.
AB  - Specific extinction procedures were matched to the function of two target
      behaviors displayed by the same individual, with results indicating that the
      matched extinction procedure suppressed the behavior for which it was designed.
      One of the target behaviors was exposed to an irrelevant extinction procedure,
      which produced no beneficial effects. These results support previous research
      indicating the need to match extinction procedures to the function of problem
      behavior.

PMID- 9757586
TI  - Assessment of stimulus generalization gradients in the treatment of self
      injurious behavior.
AB  - Descriptive and experimental analyses suggested that the self-injurious behavior
      (SIB) of a 10-year-old girl with severe mental retardation was maintained by
      attention. Additional analyses identified physical contact as the type of
      attention maintaining SIB; therefore, we hypothesized that physical proximity of
      an adult was a discriminative stimulus for SIB. Based on these findings, we
      systematically varied the distance between the participant and a therapist to
      assess stimulus generalization. Results showed that rates of SIB varied relative
      to the distance between the participant and therapist; the highest percentage of
      SIB occurred with the therapist positioned less than 0.5 m from the participant.
      Treatment consisted of placing the therapist at a specified distance (9.0 m) from
      the participant (during low-attention situations), noncontingent reinforcement,
      and extinction.

PMID- 9757587
TI  - The use of an enhanced simplified habit-reversal procedure to reduce disruptive
      outbursts during athletic performance.
AB  - An enhanced simplified habit-reversal procedure was used with a 14-year old boy
      who presented with a long history of disruptive, angry outbursts during tennis
      matches. Initial treatment involved simplified habit-reversal procedures
      delivered in a multiple baseline design across settings. Modest results led to
      additional supporting contingencies, including response costs. Results showed
      elimination of disruptive outbursts during both nontournament and tournament
      matches and highlight the importance of adding additional supporting
      contingencies to simplified habit reversal for some self-control problems.

PMID- 9757588
TI  - Reductions in self-injury produced by transcutaneous electrical nerve
      stimulation.
AB  - Transcutaneous electrical nerve stimulation is used to reduce pain but also may
      be useful for self-injurious behavior (SIB). In the current investigation, a
      microcurrent electromedical device, classified as a transcutaneous electrical
      nerve stimulator (TENS), was applied with a man with Down syndrome who displayed
      SIB that persisted in the absence of social contingencies. Although clinically
      significant results were not maintained, a clear difference in the rates of SIB
      during active and inactive TENS was observed.

PMID- 9757589
TI  - UV light affects cell membrane and cytoplasmic targets.
AB  - For a long time DNA has been regarded as the only molecular cellular target for
      UVB and UVC. However, evidence is accumulating that ultraviolet light (UV) can
      also affect cytoplasmic and membrane structures. It has been shown that UV can
      directly affect cytoplasmatically located transcription factors, kinases closely
      located to the cellular membrane and even membrane receptors. The identification
      of additional cellular UV targets and the mechanisms by which these targets
      transduce the UV signal will increase the understanding of the biological effects
      of UV. Recently, we observed that UV can interfere with cytokine signalling and
      induce apoptosis via direct activation of apoptosis-related surface receptors.
      These findings will be briefly reviewed in the paper.

PMID- 9757590
TI  - Flow cytometric quantification of UV-induced cell death in a human squamous cell
      carcinoma-derived cell line: dose and kinetic studies.
AB  - Exposure to ultraviolet (UV) radiation and photochemotherapy induces apoptotic
      cell death in epidermal cells. In this study annexin V binding and propidium
      iodide (PI) uptake have been measured by flow cytometry to evaluate UV-induced
      cell death in the human squamous cell carcinoma-derived cell line A 431.
      Physiological and therapeutical relevant doses of UVA, UVA1, UVB, narrow-band UVB
      (311 nm) and photochemotherapy using 100 ng/ml of 8-methoxypsoralen (8-MOP) with
      UVA or UVA1 (PUVA or PUVA1) have been applied. Doses ranged from 8 to 96 J/cm2
      for UVA1 and UVA, from 8 to 128 mJ/cm2 for UVB, from 256 to 4096 mJ/cm2 for
      narrow-band UVB (311 nm) and from 1 to 16J/cm2 for photochemotherapy. Results
      show that the amount of annexin V binding, a measure of early apoptosis, as well
      as PI uptake, a parameter of ultimate cell death, are strictly correlated with
      the applied UV dose. Peak values of annexin V-positive cells are noted 12 h after
      UV exposure in all protocols and are followed by an increase of PI-uptaking cells
      with peak values at 24 h after UVA and UVA1, and 48 h after PUVA, PUVA1, UVB and
      narrow-band UVB. To compare the effect of different wavelengths and light
      sources, dose equivalents are calculated based on the induction of 50% cell death
      (as determined by PI uptake). The equivalents are 96 J/cm2 for UVA and UVA1, 16
      J/cm2 for PUVA and PUVA1, 256 mJ/cm2 for UVB and 2048 mJ/cm2 for narrow-band UVB.
      Our results establish annexin V/PI double staining as an appropriate method for
      the quantification of UV-induced cell death. Moreover, they provide a basis for
      further investigations concerning mechanisms and modifications of UV-induced
      apoptosis.

PMID- 9757591
TI  - Cellular target of UVB-induced DNA damage resulting in local suppression of
      contact hypersensitivity.
AB  - Experimental data are reviewed that lend support to the hypothesis that formation
      of DNA damage is the initiation event of local suppression of contact
      hypersensitivity (CHS) after exposure to ultraviolet (UV) radiation and that the
      antigen-presenting cell (APC) is an important target for this DNA damage.

PMID- 9757593
TI  - The potential role for urocanic acid and sunlight in the immune suppression
      associated with protein malnutrition.
AB  - Irradiation of skin by sunlight or ultraviolet B (UVB, 290-320 nm) brings about a
      downregulation of cell-mediated immunity. An action spectrum for photoimmune
      suppression in mice indicates that trans-urocanic acid absorbs UV photons and is
      isomerized to the cis-isomer in the stratum corneum. Cis-urocanic acid is
      subsequently shown to suppress cellular immunity in mice. When histidine is
      elevated in a mouse diet, a higher level of urocanic acid is detected in mouse
      skin. These mice are more susceptible to photoimmune suppression. There is
      evidence that humans and animals experiencing protein malnutrition have very high
      levels of urocanic acid and/or histidine. Urocanic acid is formed by deamination
      of histidine in one enzymatic step. We discuss the protein malnutrition of
      kwashiorkor patients. They experience suppressed immunity and disturbed histidine
      metabolism. Here, we present a testable hypothesis: one cause of the immune
      deficiency observed in humans with protein malnutrition is the photoconversion by
      UVB of increased levels of trans-urocanic acid in skin to cis-urocanic acid,
      which suppresses the cellular immune system.

PMID- 9757592
TI  - Urocanic acid and cutaneous antigen presentation.
AB  - Exposure to UVB results in the isomerization of trans-urocanic acid (UCA),
      localized in the stratum corneum, to cis-UCA. Cis-UCA can mediate at least some
      of the immunosuppressive effects of UVB, though the mechanism of cis-UCA action
      remains incompletely defined. Here, we review the evidence that cis-UCA acts
      through alterations in cutaneous antigen presentation.

PMID- 9757594
TI  - Immunobiology of lipid-modulated UV-carcinogenesis.
AB  - Previous studies have demonstrated that high levels of dietary fat exacerbate UV
      carcinogenic expression and suppress immunoresponsiveness. The latter may account
      for the former response. We have explored this possibility through T-lymphocyte
      transfer studies. Groups of HRA.HRII-c/+/Skh hairless mice were fed isocaloric
      diets containing high (12%, wt./wt.) or low (0.75%) levels of corn oil and
      irradiated 5 days/week (1.0 J cm-2/day) for 11 weeks with filtered FS-40
      sunlamps. At weeks nine and 12, enriched T-cells from high-fat donors that had
      received 11 weeks of UV were transferred intravenously to low-fat recipients.
      Median tumor times for high-fat, low-fat recipient, and low-fat groups were 15.8,
      18.5, and 21.6 weeks, respectively. The significantly (P < 0.03) shortened
      primary tumor latent period in low-fat-fed animals resulting from transfer of
      relatively low levels of T-cells derived from chronically irradiated high-fat
      donors demonstrates that the influence of dietary fat upon UV-carcinogenic
      expression is, at least partially, mediated via immunologic mechanisms. Further
      studies suggest that fat-modulated carcinogenesis can, itself, be regulated
      immunologically. A soluble T-14 (mouse squamous carcinoma cell line) cell-free
      fraction was injected subcutaneously at axillae and inguen of animals fed the
      high-fat diet during the first three weeks of UV or immediately post-UV. At week
      four post-UV, animals were challenged with T-14 cells injected subcutaneously at
      both flanks. 21 days post-challenge the tumor volumes of low-fat and high-fat
      immunized animals were zero versus 593 mm3 for the high-fat group (P < 0.007).
      Such treatment significantly (P < 0.03) increases the latent period of UV-induced
      primary tumors as well, when compared to non-treated high-fat-fed animals.

PMID- 9757595
TI  - A single exposure of solar simulated radiation suppresses contact
      hypersensitivity responses both locally and systemically in humans: quantitative
      studies with high-frequency ultrasound.
AB  - Ultraviolet radiation (UVR)-induced suppression of cutaneous cell-mediated
      immunity plays an important role in the development of photocarcinogenesis in the
      mouse and a similar role is suspected in humans. Cell-mediated immunity is
      readily tested in vivo by measuring the contact hypersensitivity (CHS) response
      to topically applied haptens. CHS in humans is usually determine clinically, with
      a subjective scoring system. However, these subjective scores cannot be
      statistically analysed. This paper compares four methods currently used to
      quantify CHS elicitation responses in humans. The data show that ultrasound
      images provide the most accurate and reproducible measurements of the clinically
      observed CHS response. We also demonstrate that assessment of the primary
      allergic response is a useful indicator of the magnitude of the elicitation
      response and can be used to avoid severe CHS reactions in volunteers. There are
      few human studies investigating the effects of solar simulated radiation (SSR)
      exposure on immunosuppression. In this study we demonstrate SSR is highly
      immunosuppressive in all subjects tested. Irradiating a small area of skin with a
      single exposure to 3MEDs of SSR completely suppressed CHS both locally (12/12
      volunteers) and systemically (10/12 volunteers). Our data do not support a role
      for a genetic susceptibility to UVR-induced immunosuppression in humans.

PMID- 9757596
TI  - Efficacy of micronized titanium dioxide-containing compounds in protection
      against UVB-induced immunosuppression in humans in vivo.
AB  - Micronized pigment-containing sunscreens may provide a good alternative to
      chemical sunscreens in protection against ultraviolet (UV) B-induced
      immunosuppression. The metal particles in these products are likely to remain on
      the skin surface where they can offer broadband protection for both the UVA and
      UVB regions. We have tested the protective capacity of three titanium dioxide
      (TiO2)-containing compounds in humans in vivo. The effect on sunburn cell
      formation has been investigated using transmission electron microscopy, while the
      mixed epidermal cell lymphocyte reaction (MECLR) has been used as a model for
      immunosuppression. Furthermore, the influence of titanium on the integrity of the
      stratum corneum barrier (intercellular lipids and desmosomes) has been examined
      using freeze fracture electron microscopy. We find that all three compounds
      protect against sunburn cell formation. The immunoprotection studies show that
      one of the three compounds does not prevent UVB-induced changes of the MECLR
      responses. Application of this compound without subsequent UVB irradiation also
      induces a significant decrease of the MECLR responses. Moreover, the same
      compound affects the intercellular lipid layers, and desmosomes cannot be
      detected. The deleterious effect of this compound is probably caused by an
      incomplete hydrolysis during the TiO2 synthesis. Our findings indicate that
      micronized pigment-containing compounds can offer good protection against short
      term UVB-induced immunomodulation in humans in vivo. However, accurate screening
      of the synthesis of these compounds is a prerequisite for their safe use as
      sunscreening agents in human subjects.

PMID- 9757597
TI  - Enhancement of tumour response to photodynamic therapy by adjuvant mycobacterium
      cell-wall treatment.
AB  - Mycobacterium cell-wall extract (MCWE) is a potent non-specific immunostimulant
      that elicits a local inflammatory response associated with antitumour activity.
      Tumour-localized administration of MCWE has been examined as an adjuvant to
      photodynamic therapy (PDT) mediated by the photosensitizers Photofrin,
      benzoporphyrin derivative monoacid (BPD), metatetrahydroxyphenylchlorin (mTHPC),
      or zinc (II)-phthalocyanine (ZnPc). A single MCWE treatment, given immediately
      after light treatment of murine EMT6 tumours, potentiates the curative effect of
      PDT. A similar enhancement of tumour response to Photofrin-based PDT is obtained
      with the live Bacillus Calmette-Guerin (BCG) vaccine. Despite differences in the
      kinetics/intensity of damage induction to tumour microvasculature and other
      characteristics underlying the mechanism of antitumour activity of Photofrin,
      BPD, mTHPC and ZnPc, there appear to be no marked differences in the therapeutic
      benefit of adjuvant MCWE therapy combined with the PDT mediated by these various
      photosensitizers. This may be related to the fact that MCWE elicits a wide range
      of immunomodulatory effects that could amplify and sustain the
      inflammatory/immune responses triggered by PDT. The enhancement of inflammatory
      effector cell activity is indicated by the increased infiltration of neutrophils
      and other myeloid cells at the expense of malignant cells found in the MCWE plus
      mTHPC-based PDT treatment group compared to the PDT-only group.

PMID- 9757598
TI  - Therapeutic photoimmunology: photoimmunological mechanisms in
      photo(chemo)therapy.
AB  - Ultraviolet radiation, either alone or in combination with photosensitizing
      agents, is widely used for the treatment of skin diseases. The efficacy of photo-
      and photochemotherapeutic modalities is thought to result, at least in part, from
      the induction of immunomodulatory effects. In particular, UV radiation has been
      shown to affect (i) the production of soluble mediators, (ii) the expression of
      cell-surface receptors and (iii) to induce apoptosis in pathogenetically relevant
      cells. UVB radiation-induced immunomodulatory effects are limited to the
      epidermis, whereas UVA radiation affects both epidermal and dermal cell
      populations. UVB and UVA radiation can exert essentially identical
      immunomodulatory effects, which result, however, from different photobiological
      mechanisms.

PMID- 9757599
TI  - Effects of armrests on workload with ten-key operation.
AB  - The constrained posture used for work using a visual display terminal (VDT), such
      as data entry, can produce static muscular fatigue. Based on the application of
      ergonomic principles, we conducted an experiment using a prototype VDT chair
      designed with an armrest adjustable to heights from 22 to 28 cm. The experiment-
      conducted to assess the static muscular strain based on varying heights of the
      armrest and distance from the keyboard--was performed with male subjects. The
      subjects were asked to input five-figure numbers using the 10 keys arranged on
      the right side. Using a surface electromyogram, we measured the strain imposed on
      the arm and the shoulder. This was followed up with a performance, weight-loading
      onto the armrests and a questionnaire. Results show that use of armrests is
      effective for the alleviation of muscles in one-handed keyboard operation where
      operators work on a desk whose height is unadjustable according to their body
      height or where operators are unable to rest their wrist on the desk. A chair
      with height-adjustable armrests is considered desirable when used by several
      people.

PMID- 9757600
TI  - A new aspect of the carotid body function controlling hypoxic ventilatory decline
      in humans.
AB  - Ventilatory response to eucapnic sustained mild hypoxia was measured in one
      patient with unilateral and three patients with bilateral carotid body (CB)
      resection (defined UR and BR, respectively). The profile of ventilatory response
      in UR patient was initially augmented then gradually declined (biphasic pattern)
      as generally seen in normal subjects although the absolute magnitude was
      substantially low. On the other hand, biphasic pattern was disappeared in all
      three BRs. Lack of hypoxic ventilatory decline (HVD) in the late period of
      sustained hypoxia was in marked contrast to that reported in the anaesthetized
      and CB-denervated animals whose ventilation was severely depressed lower than the
      pre-hypoxic control level. In view of recent knowledge that the analogous mild
      hypoxia in normal animals and humans elicits an useful adaptation to economize
      energy expenditure with maintaining reversible excitability in control of
      respiration, BR patients were considered to have lost this ability. We conclude
      that in awake humans the CB not only stimulates ventilation but also controls the
      degree of subsequent HVD during sustained hypoxia.

PMID- 9757601
TI  - Comparison of cardiac response to managerial workload between men and women.
AB  - The aim of the study, was to estimate the reaction of selected circulatory system
      parameters to psychic workload in industrial managers and to answer the question
      whether may affect this reaction. The study was performed in 23 men (mean 46 +/-
      6 years of age) and 16 women (mean 42 +/- 6 years of age), employed as executives
      in a large industrial plant. The subjects had their 24-h ECG recorded using
      Medilog 3000 (Oxford). The ECG recordings were classified as pathological
      according to the standards of Bjerregaard. Heart rate was calculated for working
      time, leisure time and sleep. The subjects were also asked to estimate the
      perceived psychic load according to a method involving subjective estimation of
      work-demands and of an ability to cope with them. Generally, the subjects
      reported high work demands, but coping abilities were higher than work demands.
      Both in the men and women, a relationship was found between the intensity of
      subjective estimation of psychic load and heart rate response. However, the
      reaction of the circulatory system to the psychic workload in men was long
      lasting (its effects continued until late at night); in women it was more direct
      (only during work). The frequency of abnormalities in 24-h Holter ECG recordings
      for both test groups was not very high, a little higher in men (30%) than in
      women (25%), and was comparable with the frequencies in selected general
      population groups. Our results may indicate that mental workload of the
      managerial staff, does not cause increased frequency of ECG abnormalities.
      However, in view of the fact that cardiovascular diseases are more frequent among
      men than among women, different reaction of the circulatory system to workload
      should also be accounted for in an attempt to explain the sources of that
      phenomenon.

PMID- 9757602
TI  - The effect of high-salt diet intake on muscular exercise ability in young
      Japanese women.
AB  - This study was designed to test whether high-salt diet intake has some acute
      impaired effect to the muscular exercise ability due to the calcium deficit in
      muscle cell via the accelerated sodium-calcium exchanger. Six healthy young
      Japanese women (aged: 22.3 +/- 1.9 yr) performed two types of muscle strength
      tests and ramp mode cycle ergometer exercise until exhaustion after normal- (NaCl
      is approximately 5.6 g) and high-salt (21.0 g) controlled diet intake on two
      separate days in random order. The urinary sodium excretion sampled during 12
      hours on the high-salt diet day was significantly higher compared to that of
      normal-salt diet day (3301 +/- 992 vs 1595 +/- 540 mg; P < 0.05), while there was
      no substantial difference between the urinary calcium excretion in high- and
      normal-salt diet days (58.6 +/- 19.7 vs 55.0 +/- 17.2 mg; ns). There were no
      significant differences in back strength, repeated maximal hand grip exercise
      ability, and VO2max and duration time during ramp exercise between high- and
      normal-salt diet conditions. It was concluded that high-salt diet intake even
      exceeding 20 g per day had substantially no acute effect on muscular exercise
      ability in young Japanese women.

PMID- 9757603
TI  - Usefulness of computer-assisted portable EEG recorder for field work in applied
      human science.

PMID- 9757604
TI  - A preface to the discussions in gender difference.

PMID- 9757605
TI  - Harmony in men and harmony in women.

PMID- 9757606
TI  - Men's time, women's time--sex differences in biological time structure.

PMID- 9757607
TI  - Male brain and female brain.

PMID- 9757608
TI  - The brave New World of advanced practice: credentialing and privileging.

PMID- 9757609
TI  - Caught in the cross fire of change: nurses' experience with unlicensed assistive
      personnel.
AB  - Under tremendous pressure to contain costs, most U.S. hospitals are radically
      altering the composition and skill mix of their staff, thinning their skilled
      registered nurse (RN) ranks, and often substituting them with minimally trained,
      lower paid, unlicensed assistive personnel (UAP). Twelve staff nurses were
      interviewed to illuminate the experience of working with UAP, who function
      largely in untested, expanded roles. Only two nurses viewed this experience
      positively; the rest were either opposed to or had strong reservations about UAP
      use. Confusion and emotional turmoil predominated as these nurses struggled to
      maintain safe, comprehensive care with the assistance of UAP who were often
      ambivalent and sometimes dangerously inept.

PMID- 9757610
TI  - Women's knowledge of osteoporosis.
AB  - Osteoporosis affects one in four women over the age of 65 and is a major cause of
      hip fractures that place women in nursing homes. In this study of 247 women,
      their knowledge of osteoporosis was assessed with the Facts on Osteoporosis Quiz.
      The instrument measured their responses to questions about self-care practices
      related to risk factors and preventive behavior associated with osteoporosis.
      Respondents came from occupational and primary health care settings and a health
      fair. The women ranged in age from 22 to 84 years. Findings indicated that the
      majority of women had inadequate knowledge of osteoporosis risk factors and
      preventive behavior.

PMID- 9757611
TI  - Falls in a psychiatric unit.
AB  - The purposes of this descriptive study were to document the prevalence of
      previously identified risk factors for falls in a group of acutely ill
      psychiatric patients, to determine if patients who fell differed from nonfallers
      with respect to risk factors, and to describe the circumstances surrounding falls
      that occurred on an inpatient unit. All patients admitted to an acute psychiatric
      unit during a 7-month period were entered into the study (N = 197). Twice a day,
      nurses who worked on the unit completed a fall-risk factors checklist for each
      patient. When a fall occurred, an additional instrument designed to measure
      circumstances associated with the fall was completed. The most frequently
      occurring risk factors were clinical diagnoses of depression and confusion or
      disorientation. Seventeen patients fell during their hospitalization. Compared
      with nonfallers, patients who fell were more likely to have a previous history of
      falls, generalized weakness, confusion or disorientation, difficulty with
      mobility or walking, elimination problems, and temperature elevation. Analysis of
      circumstances surrounding falls showed that the majority of falls occurred when
      patients were attempting to get out of bed, walk to the bathroom at night, or
      change from a sitting to a standing position. Findings from this research can be
      used to identify psychiatric patients who are at risk for falls during their
      hospitalization.

PMID- 9757612
TI  - Clinical nurse researchers' perceptions of hospital nursing research committees:
      results of a national survey.
AB  - A growing body of literature portrays sharpening controversy over the appropriate
      roles and functions of hospital nursing research committees (HNRCs). This
      descriptive study examined 139 clinical nurse researchers' experiences with
      HNRCs. Nurse researchers who were members of HNRCs had more positive attitudes
      towards HNRCs on all three scales of the HNRC-Questionnaire than nurses who were
      not members of HNRCs. Researchers who were prepared with Master's degrees had
      more positive attitudes on the HNRC Role Scale than researchers with doctoral
      degrees. Narrative comments written on the questionnaire reflected a substantial
      diversity of opinions regarding HNRCs. The results suggest that novice,
      nondoctorally prepared researchers may perceive the assistance of some HNRCs as
      beneficial, whereas doctorally prepared researchers tend to perceive them as
      obstacles.

PMID- 9757613
TI  - Quality of life in systemic lupus erythematosus.
AB  - This study reports the impact of systemic lupus erythematosus (SLE) on the
      quality of life of 37 SLE patients by using two quality of life (QOL)
      instruments, the Sickness Impact Profile and the Arthritis Impact Measurement
      Scale 2. Findings suggested that SLE affects all areas that are considered
      essential for QOL including alertness behavior, recreation/pastime, sleep and
      rest, home management, social interaction, and emotional balance. Findings
      suggest that in the management of chronic illnesses such as SLE, QOL assessments
      may provide health care professionals with data that would enhance the likelihood
      of designing holistic interventions.

PMID- 9757614
TI  - Health problems and health actions among community-dwelling older adults: results
      of a health diary study.
AB  - This study examined the health problems and health actions reported by a sample
      of older adults (N = 60) who maintained health diaries over a 4-week period. The
      diary sample was 78% (n = 47) White; 52% (n = 31) were women, with a mean age of
      75 years (SD = 5.3). Content analysis was used to examine the types of health
      problems reported in the diaries, which health problems were likely to be
      considered an illness, and what health actions were reported. Respondents
      reported an average of four different types of health problems over the 4-week
      diary period. There were differences in symptom reports related to gender, age,
      or race. The most frequently reported health problems were musculoskeletal
      problems (n = 38), runny nose and respiratory problems (n = 24), gastrointestinal
      problems (n = 22), and headaches (n = 22). Only 36% of all health problems were
      considered to be illnesses. Subjects recorded a number of health actions in
      response to their health complaints, including over-the-counter (OTC) medication
      use (83%), prescription medication use (53%), self-care activities (72%), and
      professional consultation (43%). Specific strategies that subjects used to deal
      with various health problems, implications of the findings, and the usefulness of
      health diaries as a clinical tool are discussed.

PMID- 9757615
TI  - Recruitment and retention of women in nontherapeutic clinical trials.

PMID- 9757616
TI  - Research interest groups: an approach to integrating research into the practice
      setting.

PMID- 9757617
TI  - Cerebral lymphomas in AIDS. Neuropathological study.
AB  - A morphological analysis was done of 15 cases of malignant cerebral lymphomas
      selected from the material of 160 brains of patients, who died in the course of
      full-blown acquired immune deficiency syndrome (AIDS) during the period of 1987
      1997. Cases with cerebral lymphomas comprised 9.4% of the whole collection. There
      were 13 males and 2 females in the studied group. The patients age ranged from 25
      to 61 years. In 10 cases lymphomas were localized solely in the central nervous
      system, and in further 4 they were accompanying systemic neoplastic process. In
      one case lack of clinical and autopsy data did not permit classification of
      neoplasm to the primary or to the secondary group. In 13 cases immunophenotype of
      the lymphomas was characterized by immunohistochemical methods. In 11 cases
      neoplastic cells originated from B cells line and in 2--from T cells line. In 10
      cases lymphomas were found in macroscopic examination, in the remaining 5 cases
      they were disclosed at the brain histopathology. The dynamics and extensiveness
      of the neoplastic process were different in particular cases. In most of them the
      process was multifocal and manifested in the form of diffuse proliferation,
      formed tumors with changing nature of their delineation and as multilayer
      perivascular cuffs. The characteristic feature of diffuse neoplasmatic growth was
      the appearance of large coagulative necroses in the central parts of tumors.
      Neoplastic foci were localized most often in the cerebral hemispheres (white
      matter, basal ganglia, periventricular regions), less frequently in the brain
      stem and cerebellum. In one case diffuse lymphoid growth involved selectively
      leptomeninges. In most of the cases leptomeningeal infiltrations accompanied
      large parenchymal neoplastic foci. The most striking feature of our collection
      consisted in concomitance of cerebral lymphomas with HIV-specific brain pathology
      and/or opportunistic infections mostly of viral etiology. Their frequency was
      much higher than in cases of AIDS without cerebral lymphomas. Another finding
      which seems to be worth mentioning was the appearance of morphological exponents
      of various pathological processes such as for instance multinuclear giant cells,
      CMV inclusions within neoplastic tissue. The relatively frequent presence of
      numerous HIV-specific giant cells on the periphery of lymphomatous tumors
      suggests pathogenetic participation of immune deficiency virus in the
      blastomatous transformation of lymphoid cells within the central nervous system.

PMID- 9757618
TI  - Olfactory neuroblastoma (esthesioneuroblastoma) and esthesioneuroepithelioma:
      histologic and immunohistochemical study.
AB  - Two cases of olfactory neuroblastoma (ONB) representing two morphological
      variants of the tumor are described. Case 1 exhibited a neuroblastoma-like
      histological pattern corresponding to the usually reported type of ONB--the
      esthesioneuroblastoma, whereas in case 2 a very rare variant of ONB-the
      esthesioneuroepithelioma was recognized. The histological and immunohistochemical
      differences between the cases are discussed with regard to still controversial
      opinions concerning the subclassification of ONB and the histogenesis and
      clinical prognosis of these tumors.

PMID- 9757619
TI  - Does the pathological factor in amyotrophic lateral sclerosis (ALS) damage also
      astrocytes?
AB  - Introduction of immunocytochemical reaction to glial fibrillary acidic protein
      (GFAP) made possible more accurate estimation of astrocytes reactivity in various
      diseases of CNS, among others, in amyotrophic lateral sclerosis (ALS). Lack of
      present studies concerning reactive astroglia in spinal cord, inclined us to
      examine the reaction of astrocytes in cervical, thoracic and lumbar spinal cord.
      Material included 11 sporadic ALS patients. Sections of formalin-fixed, paraffin
      embedded tissue were stained with hematoxylin and eosin, Kluver-Barrera method
      and with antibody against GFAP. In all cases various degree of nerve cells loss
      in the anterior horn, pigmentary degeneration of remaining neurons, the pallor of
      myelin in the white matter of anterior and lateral columns were observed. In a
      part of cases background tissue rarefaction within anterior horn was seen.
      Intensity of morphological changes within anterior horns made possible to divide
      material into two groups and separate one senile case. Very intensive neuronal
      changes associated with weak reaction of astrocytes in the anterior horn allow us
      to pose the hypothesis of influence of an unknown pathological factor on both
      anterior horn neurons and astrocytes.

PMID- 9757620
TI  - Quinolinic acid and sigma receptor ligand: effect on pyramidal neurons of the CA1
      sector of dorsal hippocampus following peripheral administration in rats.
AB  - Male Wistar rats, weighing 200-220 g, were used in the study. Quinolinic acid and
      racemic pentazocine were administered alone or together. Quinolinic acid was
      administered intraperitoneally (i.p.) in a dose of 60 mmol, racemic pentazocine
      intramuscularly in a dose of 2 mg/kg, once every 24 h for 8 days. The control
      group received 1 ml of saline i.p. once daily for 8 days. Pentazocine alone
      produced no signs of alteration in the hippocampal formation. Quinolinic acid
      produced neurotoxic effect in the CA1 area of the hippocampal formation. The
      presence of the dark-degenerated pyramidal cells was a common sign of a delayed
      excitotoxic effect. Pentazocine added to quinolinic acid markedly attenuated the
      neurotoxic effect of quinolinic acid. In such cases, only single dark degenerated
      cells were seen.

PMID- 9757621
TI  - The effect of Dotarizine--(Ca2+ channel blocker)--on vascular reactivity and
      ultrastructure of cerebral capillaries in animals subjected to anoxia.
AB  - Dotarizine--the novel piperazine derivative--belongs to wide spectrum Ca2+
      channel antagonists. It was reported to have strong vasodilatatory and
      antiserotoninergic activities. Comparing with other Ca2+ channel blockers
      Dotarizine was found to have lower oral toxicity. In the present study the
      influence of the oral administration of the novel compound on the blood flow
      velocity changes in different cerebral arteries--in basilar artery (BA) and
      middle cerebral artery (MCA)--was investigated under hypoxic conditions. The
      ultrastructural morphological changes of intracerebral vessels endothelium in
      treated and untreated anoxic animal groups were also demonstrated. The
      experiments were carried out on rabbits. In the experimental group 25 mg/kg of
      Dotarizine dissolved in 0.25% agar was administered orally three times at the 10
      hours' intervals. The sham group of animals was fed with agar of the same
      concentration. During anoxic conditions strong vasodilatory effects were observed
      in both investigated vessels of drug-treated animals. In the experimental group
      marked ultrastructural differences in parenchymal vessel endotheliumin comparison
      to sham group were revealed. Thus, the oral administration of Dotarizine might
      have effect on the various parts of the cerebrovascular system and can play
      significant role in improvement of various cerebrovascular disorders.

PMID- 9757622
TI  - Characterization of thiamine pyrophosphatase positive phagocytic cells in the
      neural lobe of rat pituitary.
AB  - Here, using a histochemical staining for a microglia/phagocyte marker TPP-ase
      (Murabe, Sano 1981), and an electron microscopy we characterized the population
      of pituitary phagocytic cells activated by cerebral ischemia. An intense thiamine
      pyrophosphatase (TPP-ase) activity was demonstrated in glial cells and some cells
      of blood vessels of neural lobe, late period (12 months) after experimental
      ischemia. TPP-ase positive cells were ultrastructurally identified as pituicytes,
      microglia, pericytes and perivascular cells. The product characteristic for TPP
      ase activity was seen on plasma membrane of these cells. Our electron-microscopic
      histochemical results provide strong support for a role of pituicytes, pericytes
      and perivascular cells as a phagocytic cells involved in mechanism of elimination
      of ischemically damaged axonal endings in neural lobe.

PMID- 9757623
TI  - Bilateral sciatic nerve entrapment due to weight loss.

PMID- 9757624
TI  - Massive hemothorax after low impact blunt chest trauma: a case report.

PMID- 9757626
TI  - New HIV/AIDS cases decline overall but increase among women, minorities.

PMID- 9757625
TI  - Angina and atrial fibrillation in a patient with thyrotoxicosis.

PMID- 9757627
TI  - Radiological case of the month. Acute appendicitis.

PMID- 9757629
TI  - Information and quality healthcare outpatient diabetic management project.

PMID- 9757628
TI  - Colorectal cancer--chemoprevention.
AB  - Colorectal cancer is the second leading cause of death from cancer in The United
      States. During the last fifteen years, emphasis has been placed on identification
      of high risk patients and families and outline of appropriate surveillance
      regimens for normal and high risk patients for colorectal cancer. Parallel to
      this effort, abundant clinical data has been accumulated that chemoprevention of
      colorectal cancer with nonsteroidals and aspirin may be possible. Interruption of
      prostaglandin metabolism appears to be one of the mechanisms of action but not
      the only therapeutic arm. Currently, sulindac, aspirin, calcium and selenium
      supplementation are attractive recommendations to at risk patients awaiting
      results of clinical trials. Other agents in development add excitement to the
      concept of colorectal cancer chemoprevention.

PMID- 9757630
TI  - [Cases of multiple ventricular septal defects].
AB  - We had 4 cases with multiple ventricular septal defects (VSDs) in complexed
      congenital heart disease. One of four had two separate VSDs detected by two
      dimensional echocardiography before operation. Second of four had additional
      infundibular muscular VSD which was detected by echocardiography in the intensive
      care unit (ICU) after patch closure of a perimembranous VSD. The third case had
      two additional VSDs of inlet muscular and subaortic septum detected by
      transesophageal and direct echocardiography during reoperation, beside a
      subpulmonary VSD which was originally diagnosed before Jatene operation for
      double outlet right ventricle. The fourth case had multiple trabecular muscular
      VSDs diagnosed by postoperative angiography soon after Rastelli operation. Since
      these additional multiple VSDs compromise the postoperative hemodynamics if those
      are unrecognized, it is indispensable to detect all VSDs before operation, using
      transthoracic and transesophageal echocardiography.

PMID- 9757631
TI  - [Application of heparin-coated PCPS for traumatic cardiac rupture: report of a
      case].
AB  - Application of heparin-coated percutaneous cardio-pulmonary support system (PCPS)
      for a case with traumatic cardiac rupture is reported. A 50-year-old woman, who
      was injured in the traffic accident, was admitted to our hospital. Her
      consciousness was not alert in circulatory collapse. Echocardiography showed
      cardiac tamponade and pericardial centesis was done followed by re-filling.
      Urgent surgical intervention was necessary. When she was brought to operating
      room, she became cardiac arrest, necessitating cardio-pulmonary resuscitation
      followed by PCPS. Under PCPS support, hemodynamic state became stable and cardiac
      laceration was repaired. Laparotomy was also done because of the distension of
      abdomen during operation, and splenectomy was necessary for the injured spleen.
      She is doing well now. Generally, it is considered to be contra-indicated to
      apply PCPS for traumatic cases which may cause bleeding tendency because of anti
      coagulant therapy. But this case report showed the possibility of application of
      PCPS for traumatic cases, if PCPS is established using heparin-coated system.

PMID- 9757632
TI  - [Coronary artery bypass grafting performed by the simple and convenient graft
      supporter].
AB  - We have experienced a simple, safe and convenient technique for supporting the
      arterial or saphenous vein graft in the coronary artery bypass grafting. This
      graft supporter is made of cotton cloth with a 50 percent polyester mix. The
      supporter is twenty centimeters long and two centimeters wide. This supporter
      provides the complete fixation of the graft without the holding by the co
      operater. Therefore the supporter allows very easy, safe and accurate graft
      anastomosis with the native coronary artery or the ascendinbg aorta. No
      complication was encountered in association with this procedure in 127
      operations.

PMID- 9757633
TI  - [Use of the radial artery graft in coronary artery bypass grafting: harvesting
      technique and spasm prevention].
AB  - The use of radial artery (RA) in coronary artery bypass grafting (CABG) has been
      increasing recently as a revival. In this report, we describe several practical
      suggestions for improving patency rate of the graft. Between April of 1997 and
      February of 1998, 41 CABGs were performed using RA graft, totalling 56
      anastomoses. The early patency rate of the graft has been 100% (graft: 38/38,
      anastomosis: 53/53). Harvesting technique: with the use of Harmonic Scalpel, it
      is possible to atraumatically harvest the vessel in a short time. Although
      longitudinal fasciotomy of the adventitia has been recently reported to be
      effective in releasing spasm, the nature of the vessel raise concern that the
      fasciotomy may even induce spasm. We hypothesize that leaving the adventitia
      intact, preserving vasa vasorum, rather than performing fasciotomy leads to
      improvement of long-term patency. Spasm prevention: we consider the body
      temperature to be the most important factor. Therefore, we utilize normothermic
      cardiopulmonary bypass (CPB). Another important factor is that the arterial CO2
      is kept at a high level during CPB. For dilation of RA graft, milrinone is used
      instead of papaverine. For the intra- and postoperative management, intravenous
      continuous administration of diltiazem was changed to nicorandil. Technically,
      essential resolution for improvement of patency rate is either to allow for large
      proximal anastomosis, or to make sequential anastomosis with another coronary
      artery which has a good run off. For these purposes, the proximal anastomosis on
      the ascending aorta seems to have the advantage over placing it on ITA.

PMID- 9757635
TI  - [A 13-year-old male with a funnel chest treated by sternal elevation].
AB  - A 13-year-old male with a funnel chest was treated by sternal elevation method.
      Reconstruction was performed by resection of rib cartilage, wedge osteotomy of
      the anterior site of the sternum, sternal elevation by placement of a titanium A
      0 plate under the sternum, and fixation of the wedge osteotomy site by a titanium
      plate. After surgery, the chest wall deformity was improved remarkably without
      complication. Although the A-0 plate was removed 19 months after surgery due to a
      break in the plate, cosmetic and functional results are now excellent 28 months
      after surgery.

PMID- 9757634
TI  - [Partial median sternotomy for pediatric cardiac surgery].
AB  - In order to minimize scar appearance and thereby improve postoperative cosmetic
      appearance for pediatric cardiac surgery patients, we performed partial median
      sternotomy incisions. A short midline incision, from 1 to 2 cm below the
      articular notch of the 2nd rib to the xiphoid process, was made. The sternum was
      divided from the xiphoid process to the articular notch of the 2nd rib. The
      thymus was mobilized and the pericardium incised longitudinally. The aorta and
      superior and inferior vena cava were mobilized to facilitate direct cannulations.
      Cardiopulmonary bypass was instituted in the usual fashion. From June to December
      1997, 14 patients between the ages of 4 days and 12 years have undergone cardiac
      repair using this technique. Cases included 7 VSD (including 4 pulmonary
      hypertension and 1 DCRV), 5 ASD, 1 ECD and and 1 DORV with mitral atresia. All
      patients were extubated within 3 hours after surgery, and there were no wound
      infections or hospital mortalities (except one 4 day old baby who died by LOS on
      the 16th postoperative day). In our experience, this approach is safe and
      provides good exposure with excellent cosmetic results.

PMID- 9757636
TI  - [Concomitant cardiac and pulmonary operation, the profits of not using cardio
      pulmonary bypass].
AB  - We performed off pump CABG (coronary artery bypass grafting) and right upper
      lobectomy with R2a lymph nodes dissection on the patient suffered from both lung
      cancer in the right S1 and stenotic lesion in the left anterior descending
      artery. Because the coronary lesion was long-segmented one, it was not suitable
      for percutaneous transluminal coronary angioplasty. To perform absolutely
      curative operation for the lung cancer, CABG was undergone simultaneously under
      off pump condition. It is generally feared that the cardiovascular surgery under
      CPB may have adverse effect for the patient with malignant lesion. Off pump CABG
      is expected to avoid such disadvantage of CPB, and thought to be suitable method
      for such a patient as we present above.

PMID- 9757637
TI  - [CABG after patch angioplasty of the left main coronary: artery report of a
      case].
AB  - A 57-year-old man was admitted to our hospital because of restenosis of the left
      main coronary trunk (LMT) after patch angioplasty for the LMT lesion. PTCA was
      repeated four times during three years after patch angioplasty, but recent
      coronary angiogram still demonstrated 75% restenosis of the LMT lesion. Double
      CABG was performed to LAD and LCX using the left internal thoracic artery and
      saphenous vein graft. Postoperative coronary angiogram revealed an excellent
      result. A careful consideration must be given to the indication of the patch
      angioplasty of the LMT lesion.

PMID- 9757638
TI  - [A case of primary cardiac malignant fibrous histiocytoma].
AB  - In this article, we report a case of primary cardiac malignant fibrous
      histiocytoma. The patient, 74-year-old female, had been treated medically for
      heart failure with minimal improvement and was referred to our hospital.
      Echocardiogram revealed two cardiac tumors in the left atrium, one of which was
      obstructing the inflow of the mitral valve. Emergent surgical resection was
      performed successfully with shortterm ICU stay, but the patient died of DIC on
      the 24th day after surgery. The pathological examination revealed malignant
      fibrous histiocytoma and this report is the 40th case report of this kind of
      primary cardiac tumor.

PMID- 9757639
TI  - [Re-do surgery with minimally invasive cardiac surgery (MICS): mitral valve
      replacement 6 years after open mitral commissurotomy].
AB  - A 60-year-old man, who had undergone open mitral commissurotomy 6 years ago,
      underwent re-do surgery (mitral valve replacement) with minimally invasive
      cardiac surgery (MICS), using lower partial sternotomy to the height of the right
      side second intercostal space. Cannulation of the heart was carried out placing a
      cannula directly into the superior vena cava and a second cannula in the inferior
      vena cava via the right atrium. Arterial return was through the ascending aorta.
      Cardioplegia was administered directly into the ascending aorta with intermittent
      perfusion. Valve replacement was performed by opening directly right side left
      atrium.

PMID- 9757640
TI  - [Superimposed infective endocarditis at anterior mitral leaflet in a patient with
      prolapsed posterior leaflet: report of a case treated with valvuloplasty].
AB  - A 64-year-old male patient was referred to our hospital for massive mitral
      regurgitation after infective endocarditis. Echocardiography revealed vegetation
      on the atrial surface of the midst of the anterior mitral leaflet. At operation
      it was found that the anterior leaflet was perforated due to infection, and the
      posterior leaflet was prolapsed resulting from elongated chordae. Anterior
      leaflet was patched with autologous pericardium, and posterior leaflet was
      repaired with rectangler resection. An autologous pericardial strip was sutured
      to posterior mitral annulus. The patient survived the operation without
      complication.

PMID- 9757641
TI  - [A case of a chronic traumatic thoracic aneurysm with compression of left main
      bronchus at the isthmus].
AB  - We report a case of traumatic thoracic aortic aneurysm found by occurrence of
      pulmonary atelectasis in the chronic phase. The patient, an 18-year-old female,
      was hospitalized with multiple trauma caused by a traffic accident. At the time
      of hospitalization, no thoracic trauma was found but a fracture of the pelvis and
      one leg was recognized. 45 days after the initial trauma, a pulmonary atelectasis
      on the left lung was found on a chest X-ray film. By chest CT and angiography,
      the pulmonary atelectasis was proved to be caused by compression of the left main
      bronchus by a traumatic aneurysm of the thoracic aorta. 55 days after the initial
      trauma, resection of the aneurysm and graft replacement was performed.
      Postoperative course was satisfactory. In conclusion, possibility of an injury to
      the thoracic aorta should be considered on the treatment for the patient with
      multiple trauma in the chronic phase as well as in the acute phase.

PMID- 9757642
TI  - [A case of constrictive pericarditis reoperated 13 years after pericardiectomy by
      left thoracotomy approach].
AB  - A 48-year-old male with constrictive pericarditis was reoperated through median
      sternotomy 13 years after pericardiectomy through left thoracotomy. Extensive
      pericardiectomy is the most important point for constrictive pericarditis.
      Therefore, we have recently chosen the median sternotomy approach which has
      advantages over the left thoracotomy approach. Namely, the cardiopulmonary bypass
      is performed in the former approach immediately if the posterior pericardiectomy
      is difficult or the coronary arterial injury happens during decortication.

PMID- 9757643
TI  - [A case of infective thoracic aortic aneurysm ruptured to the lung].
AB  - We report a successful surgical treatment of an infective thoracic aortic
      aneurysm ruptured to the left lung. A 63-year-old man who had been suffering from
      fever and cough showed twice of hemoptysis. Chest CT revealed a descending
      thoracic aortic aneurysm ruptured to the left lung. A semiemergent operation was
      performed. At operation, aneurysm of descending thoracic aorta was found adherent
      to the left lung. Aneurysmectomy with left pneumonectomy was carried out. The
      postoperative course of the patient was uneventful. Conceivably, in order to
      avoid massive intraoperative bleeding during division of dense adhesion and
      postoperative graft infection, concomitant lung resection is necessary.

PMID- 9757644
TI  - [Thoracoscopic surgery for an aged patient with T1N0 non-small cell lung cancer:
      case report].
AB  - An 85-year-old woman was referred to our hospital because of an abnormal shadow
      in the right upper lung field in chest roentgenograms. CT scans revealed a tumor,
      3 cm in diameter at the peripheral field of the upper lobe. The lesion was
      diagnosed adenocarcinoma of the lung by transbronchial lung biopsy (c-T1N0M0).
      She underwent a partial resection of he S3 in consideration of age and the
      clinical stage, by using thoracoscopic procedure. Her postoperative course was
      uneventful and she was discharged on the 14th postoperative day. Since then, she
      has been free from recurrence for the past 3 years. Thoracoscopic surgery appears
      to be useful for aged patients with peripheral early lung cancer because of low
      incidence of postoperative disability and complications.

PMID- 9757645
TI  - [A case report of small-sized peripheral lung cancer diagnosed by thoracoscopic
      biopsy].
AB  - A case who had surgical treatment for small-sized peripheral lung cancer
      diagnosed by thoracoscopic biopsy was reported. A 66-year-old female was admitted
      to our hospital because of evaluation of an abnormal shadow on chest X-ray. Chest
      CT showed that the tumor about 7 mm in diameter was situated in right S1b and
      suspected to be malignant. Transbronchial lung biopsy and brushing showed no
      malignancy. The tumor was finally diagnosed to be well-differentiated
      adenocarcinoma by thoracoscopic lung biopsy. Following this procedure, right
      upper lobectomy and lymph node dissection (R2a) were performed through postero
      lateral thoracotomy at one stage. Pathological diagnosis showed that the tumor
      was well-differentiated papillary adenocarcinoma and pathological TNM
      classification was T1N0M0. The postoperative course was uneventful and the
      patient is now doing well with no relapse at 1 year 2 months after the operation.

PMID- 9757646
TI  - [Postoperative chylothorax treated with fibrin glue and absorbent mesh: a case
      report].
AB  - A 66-year-old man was treated by graft replacement for a thoracic aortic
      aneurysm. Chylothorax occurred on postoperative day 2. In spite of cessation of
      oral intake and IVH management, chest tube drainage did not decrease, the patient
      became malnourished. A chest X-ray and CT scan revealed the massive pleural
      effusion. Reoperation assisted with a thoracoscopy was carried out for
      chylothorax on postoperative day 27. Because we were unable to find the thoracic
      duct and the leakage point, the fibrin glue and absorbent mesh was applied to
      parietal and mediastinal pleura. Four days after reoperation, the chest tube was
      removed. This method is useful for this type of a chylothorax and lymphorrhea.

PMID- 9757647
TI  - [Desmoid tumor of the chest wall: a case report].
AB  - A 45-year-old man was referred to our hospital for recurrent desmoid tumor of the
      chest wall. He underwent chest wall resection with reconstruction of Marlex mesh.
      But we could not resect it enough widely, because the tumor invaded beside left
      subclavian artery and subclavian vein, brachioflexus. So he had additional
      radiation therapy (50 gry). The patient is now doing well without recurrence 1
      year after the operation.

PMID- 9757648
TI  - [Enchondroma protuberance with destroying the rib: report of a case].
AB  - A 18-year-old female was admitted to our hospital because of a mass shadow in the
      left upper lung field on chest roentgenogram of a medical check. Computed
      tomography and magnet resonance imaging of the chest revealed a tumor which
      located in the left 5th rib, and was unclearly demarcated to the rib. Under the
      diagnosis of a rib tumor, the patient was treated by radical en bloc excision.
      The pathologic diagnosis was enchondroma protuberance of the rib. This tumor may
      be indistinguishable from osteochondroma or chondrosarcoma. Therefore, total
      resection is recommended for accurate diagnosis and absolute cure.

PMID- 9757649
TI  - [A resected case of a bronchiolo-alveolar cell carcinoma of the lung accompanying
      pneumonia-like shadow on chest roentgenogram].
AB  - A 67-year-old female was admitted to our hospital because of pneumonia-like
      shadow on chest roentgenogram with persistent cough and sputum of 4 months
      duration. Diagnosis as lung cancer was delayed more than 4 months. She showed
      fever and inflammatory reactions. Antibiotics were effective to inflammatory
      reactions, but not effective to pneumonia-like shadow. Transbronchial lung biopsy
      was useful for the diagnosis. Right lower lobectomy was performed. In this case,
      tumor extents were limited within one lobe. Tumor cells did not invade blood and
      lymphatic vessels, and extrathoracic metastases were not detected. The prognosis
      of bronchiolo-alveolar cell carcinoma was determined by intra-pulmonary tumor
      extent. Based on a comparison with the outcome of unresected cases, bronchiolo
      alveolar cell carcinoma limited within one lobe should be surgically resected.

PMID- 9757650
TI  - [Esthesioneuroblastoma: review of literature and case report].
AB  - On the base of literature and the own cases the author showed occurrence,
      pathomorphology and treatment of the esthesioneuroblastomas.

PMID- 9757651
TI  - [Diagnostic problems in cases of neck tumors].
AB  - The authors present diagnostic problems that are faced in cases of neck tumours,
      despite the application of modern examination methods. The above mentioned
      problems also concern pathological diagnostics. Emphasis is placed on the
      opportunity of achieving unbelievable results in ultrasonographic study and
      aspiration biopsy in cases of lymphoma and Hodgkin's disease.

PMID- 9757652
TI  - [Tumor markers in monitoring of neoplasms].
AB  - Prophylaxis, diagnosis, radical treatment and monitoring have a basic
      significance in the clinic of head cancers. The aim of the clinical course of
      malignant disease preferred prematurely detection of the recurrence. In the
      monitoring wide applications have tumor markers. The authors present the results
      on the sensitivity of seven biochemical tumor markers (AFP, Ca-9, CEA, TPA, NSE,
      ferritin and SCC) in 42 patients with neoplasm of the head. The sensitivity is
      for AFP-0%, CEA-10%. Attention was drawn to the relatively high sensitivity for
      TPA, NSE, ferritin and SCC, particularly for the neoplasms of oral cavity (TPA
      45%, NSE-68%, ferritin-38%, SCC-55%) and the pharynx (Ca 19-9-38%, TPA-63%, NSE
      62%, ferritin-42%, SCC-83%).

PMID- 9757653
TI  - [Dilemas in the evaluation of post-radiation lesions of the larynx].
AB  - The authors analyse the post-radiation lesions in larynx taking into
      consideration the cases of coexistence with residual or recurrent tumour. They
      underline the difficulties in obtaining a true picture of the condition of the
      larynx on the basis of histopathological examination. In a number of cases
      repeated histopathological examinations delayed the surgical treatment and thus
      caused in some them that the patient's chance to be cured was lost. The authors
      characterise clinical symptoms with strongly suggest the presence of tumour in
      those cases.

PMID- 9757654
TI  - [Clinical evaluation of patients with bilaterally increased lymph nodes in
      laryngeal cancers].
AB  - Clinical evaluation of patients with laryngeal carcinoma and bilateral neck nodes
      examined intraoperatively was performed. Clinical and histopathological analysis
      of treatment methods and results was carried out.

PMID- 9757655
TI  - [Complications and failure after partial laryngectomy].
AB  - The frequency and type of failures and complications after 259 partial
      laryngectomies in patients treated for cancer of larynx in Otolaryngology
      Department of Medical University of Lodz from 1980 to 1996 were evaluated. Among
      the failures a local and nodal recurrence, a distant metastasis and a second
      primary malignant tumor were taken into consideration. Furthermore, among the
      complications disfunction of breathing, swallowing, voice emission and abnormal
      healing were analyzed. The most often failure was local recurrence which had been
      observed in 36 patients (13.9%) and the most often complication was a granulation
      in larynx which had been observed in 45 patients (17.4%).

PMID- 9757656
TI  - [Distant results of putting the feeding tube through wound after laryngectomy].
AB  - Authors present their own postoperative results in nourishing the patients after
      laryngectomy. Their several years' observations, based on the group of 318
      patients, were connected with the risk of the postoperative complications. In
      proposed way of nourishing (introduced by B. Latkowski) the point is in putting
      the nutritive drain not through the nose, but directly through the cutting during
      laryngectomy. The main aim of the research was presenting good points of this
      method and existence of no complications with the most dangerous--fistulas.

PMID- 9757657
TI  - [Myxoid liposarcoma of the larynx].
AB  - The paper presents a rare case of tumor--liposarcoma myxoides of untypical
      location--in the area of subglottic larynx. Diagnostic problems that resulted in
      erroneous recognition of the case, leading to improper treatment, are discussed.

PMID- 9757658
TI  - [Rare malignant tumors of the larynx].
AB  - The study presents rare neoplasms of larynx. The authors introduce epidemiology,
      clinical history and medical treatment in two cases of adenocarcinoma and one
      case of sarcoma. The authors call attention to high malignancy of tumors, early
      metastases to neck lymph nodes and distant metastases.

PMID- 9757659
TI  - [Laryngeal chondrosarcoma].
AB  - The authors showed the laryngeal chondrosarcoma in own materials.

PMID- 9757660
TI  - [Multi-stage anatomical-functional reconstruction in surgical treatment of cancer
      of the mouth floor and tongue].
AB  - Authors present multistage surgical treatment of cancer disease with its radical
      dissection and anatomical reconstruction of risected tissue diminution and
      consecutive functional reconstruction of organs and tissue elements in later
      stage.

PMID- 9757661
TI  - [Delto-pectoral flap in reconstruction of esophagus after laryngectomy].
AB  - The authors present the case of 67 years old male with carcinoma of larynx and
      hypopharynx. The tumor was resected by total laryngectomy enlarged by partial
      resection of hypopharynx and esophagus. The reconstruction of hypopharynx and
      esophagus was made using deltopectoral flap because with a successful effect.

PMID- 9757663
TI  - [On diagnosis and treatment of parotid tumors].
AB  - The authors showed diagnosis and treatment of parotid tumours.

PMID- 9757662
TI  - [Malignant adenolymphoma-oncocytic adenocarcinoma of the parotid gland].
AB  - The authors present an extremely rare case of a malignant form of parotid gland
      adenolymphoma treated by surgical intervention. Further, diagnostic problems and
      methods of treatment are discussed as well as unsuccessful course of the disease,
      due to extensive, distant metastases.

PMID- 9757664
TI  - [Salivary gland tumor in authors' material].
AB  - The aim this work was to analyze the operated salivary gland tumors, taking into
      consideration the age and the sex of the patients. From 1980 to 1996 74 patients
      were operated including 40 women and 34 men, aged 21-78. Out of those 74 salivary
      gland tumors which were operated, conservative operation was carried out in 62
      patients (85.2%) while in 11 patients (14.8%) it was radical operation. Most of
      the patients who underwent the operation were at the age between 31 and 60
      (77.1%). In most cases--77.2% we had to do with mixed tumor of parotid gland and
      in 4% of submaxillary gland. Postsurgery complications in the from of complete
      facial paralysis were shown in 14.8% of the patients.

PMID- 9757665
TI  - [Head and neck lymphomas in the material of the ENT department of Municipal
      Hospital in Gdynia in 1977-1996].
AB  - The authors present data relating to patients with malignant lymphoma of the head
      and neck diagnosed at the ENT Department, Municipal Hospital in Gdynia, during
      the years 1977-1996. The material is analysed in relation to the sex and age of
      the patient and the localisation of tumour. Some cases are presented in detail
      depending on localisation or difficulties in diagnosis (lymphoma of the larynx
      and ethmoidal sinus).

PMID- 9757666
TI  - [Non-Hodgkin's lymphoma: diagnostic problems].
AB  - The aim of this article was to describe rarely occurred non-Hodgkin's lymphomas
      from peripheral lymphocyte T. Epidemiology, course of the disease and
      difficulties of diagnostic was described with the special regards of early
      diagnostic.

PMID- 9757667
TI  - [Thyroid neoplasm with symptoms of carotid body tumor].
AB  - The authors present a case of thyroid cancer manifestating itself as carotid body
      tumor. Fine needle biopsy performed twice and an arteriography suggested this
      diagnosis.

PMID- 9757669
TI  - [Atypical localization of polymorphic adenoma].
AB  - The authors described 3 cases of adenoma polymorphic located in other than major
      salivary gland sitea.

PMID- 9757668
TI  - [A skull base tumor complicated by rhinorrhea].
AB  - The authors presented a case of rare skull base tumor complicated by rhinorrhoea.
      Diagnostic procedures and surgical treatment by laryngo-neurosurgical team was
      described.

PMID- 9757670
TI  - [Laser surgery in otolaryngology].
AB  - The paper presents contemporary methods of using different kinds of lasers for
      surgical interventions in otolaryngology. It contains data concerning the
      development of laser techniques, the discussion of laser radiation and
      classification of different types of lasers. Basing on the authors' personal
      experience and the literature, the review of indications and contraindications
      for otolaryngological laser treatment has been made and the best kind of laser
      has been chosen. The risk factors of laser treatment, both for patients and for
      medical staff including various complications is stressed. Moreover, early and
      distant treatment results are presented as well as the advantages of using laser
      beam and adverse effects. The problems of applying laser treatment in
      anaesthesiology are discussed.

PMID- 9757671
TI  - [The use of thermography for the laryngeal diagnosis].
AB  - Authors presented possibility of clinical appliance of the M 4128 thermocamera in
      monitoring thermal changes of the skin and mucosa in upper respiratory tract
      diseases in patients treated at ENT Department Medical University of Lodz. Basing
      on the obtained results authors conclude usefulness of thermocamera in diagnosis
      of the head and neck tumors and inflammatory diseases and monitoring of the
      photodynamic therapy.

PMID- 9757672
TI  - [The use of CO2 laser in the treatment of leukoplakia of the oral cavity].
AB  - During the period from 1992 to 1996 in the Otolaryngological Clinic of the
      Medical Academy in Bydgoszcz 20 patients with leucoplakia of the oral cavity were
      hospitalized. The treatment with the CO2 laser was used. Depending on the kind of
      lesion single or continuous ray of the power 6-15 W were applied. The patients
      were divided into 3 groups according to the kind of leucoplakia: patients with
      simple leucoplakia, patients with nodular leucoplakia, Patients with verrucous
      leucoplakia. According to the size of the leucoplakia area: lesions of 1 cm
      diameter, lesions of 2 cm diameter, lesions of over 2 cm diameter were
      differentiated. In the case of simple leucoplakia the laser ray of 5-6 W power
      was applied, in nodular leucoplakia 6-10 W, and in verrucous leucoplakia the
      power was 10-15 W. In this work the results of the 5 years observation are
      presented.

PMID- 9757673
TI  - [14 years of experience in using endoscopic laser microsurgery for various
      laryngeal diseases].
AB  - The author presented his own experience concerning the indication and limitation
      of the method of laser CO2 application in endoscopic microsurgery based on 14
      years experience in research on treatment of various larynx diseases at 2500
      patients.

PMID- 9757674
TI  - [Functional voice evaluation after Reinke's edema treated with CO2 laser and
      Kleinsasser's microsurgery].
AB  - The authors performed functional evaluation of voice in 124 patients treated with
      microsurgery due to oedema Reincke in the years 1991-1994. In 90 patients surgery
      was performed with CO2 laser microsurgery and in 34 patients with
      microlaryngoscopy according to Kleinsasser. The picture of larynx was registered
      and evaluated with help of laryngovideostroboscopy. The voice status was
      evaluated in phoniatric examination, registered on tape and submitted to acoustic
      analysis. No correlation between method of surgical treatment and quality of
      voice was observed. However, significantly worse quality of voice was noted in
      those smoking after surgery.

PMID- 9757675
TI  - [Microsurgery of larynx in own material at the Otolaryngological Clinic of the
      Central Clinical Hospital at the Military School of Medicine].
AB  - In paper authors presented own material of performed in the years 1991-1996 in
      Clinic of Otolaryngology Central Clinical Hospital Military School of Medicine
      microsurgical operations of larynx (classic and laser). The authors postulate
      that indications for clinical diagnostic and therapeutic procedures should be
      considerably extended in diseases of larynx. This operating technique
      considerably shorten hospitalization period of patients and significantly
      contribute to an increase of percentage of early diagnoses of cancer of the
      larynx.

PMID- 9757676
TI  - [The use of the CO2 laser in the treatment of laryngostenosis and
      tracheostenosis].
AB  - The authors show the possibilities of using the laser CO2 in treatment of both
      laryngostenosis and tracheostenosis in 54 patients. In the article various forms
      of treatment of laryngostenosis and tracheostenosis as well as the results of the
      therapy have been presented. On the basis of the cases treated so far, the
      prospects of using the laser CO2 in this form of treatment have been found
      limited. The best results have been attained in treating the narrowings on a
      small surface. In case of complex laryngostenosis and tracheostenosis, the most
      effective treatment has been obtained by using the combination of the laser
      microsurgery performed on the larynx area along with the surgical resection of
      the narrowed segment of the trachea and the fusion "end to end". In some cases
      good results have been achieved by using the laser CO2 to remove postoperative
      scars of the larynx after partial laryngectomies.

PMID- 9757677
TI  - [Application of CO2 laser surgery in the treatment of rhinophyma].
AB  - The authors present the method of combined treatment of rhinophyma (surgery and
      laser CO2). The advantages of this method are good cosmetic result, small
      intraoperating bleeding and short time of healing the wound.

PMID- 9757678
TI  - [Laser surgery and interferon in the treatment of laryngeal papilloma].
AB  - The laryngeal papilloma is very doubtful disease in children. The unknown
      etiology cause that there wasn't complete radical method in the treatment of
      laryngeal papilloma. Authors presented a case of 11 years old girl with recurrent
      laryngeal papilloma, who was treated twice with laser microsurgery without
      successful results. The 6 months application of interferon alfa after third laser
      microsurgery resulted in more than one year of remission of the disease.

PMID- 9757679
TI  - [Dacryocystorhinostomy by endonasal way].

PMID- 9757680
TI  - [Endoscopic surgery of the sinus: own experiences].
AB  - In the Clinic of Otolaryngology Central Clinical Hospital Military School of
      Medicine in Warsaw in years 1992-1996 there were performed 187 endoscopic
      operations of nose and paranasal sinuses. Authors analised own material paying
      particular attention to indications, benefits and failures of these operations.
      Authors postulate that indications for clinical diagnostic and therapeutic
      procedures of this technique should be considerably extended in diseases of nose
      and paranasal sinuses. The application of endoscopic sinus surgery in our Clinic
      decreased the number of more extended operations of paranasal sinuses.

PMID- 9757681
TI  - [Theoretical basis for the antibiotic therapy of the upper part of the
      respiratory system].
AB  - The paper presents the views on the etiology of infections in the respiratory
      system. Beside the so called "old pathogens" such as Streptococcus pneumoniae,
      Haenophilus influenzae, Moraxella catarrhalis, "atypic" microorganisms are
      becoming more and more important, i.e. Mycoplasma pneumoniae, Legionella
      pneumophila, Chlamydia pneumoniae. Mixed flora with aerobic and anaerobic
      bacteria is observed in chronic infections. Viral infections facilitate bacterial
      infections. Antibiotic used first should be active against the "old" and "new"
      pathogens. Future prospects are set on macrolides such as clarythromycin.

PMID- 9757682
TI  - [Zinnat in ambulatory treatment of acute pharyngitis and otitis media in adult
      patients].
AB  - The aim of this work was the assessment of therapeutic efficacy of antibiotic
      Zinnat (Cefuroksym Aksetyl) in ambulatory treatment of acute pharyngitis and
      otitis media in 20 adult patients, aged 21-36. The efficacy of Zinnat was
      assessed on the basis of the smear from the throat and external auditory meatus
      to examine the culture and antibiogram, fever chart and self-assessment chart of
      symptoms which were assessed from 0 to 4. It was shown that Zinnat is an
      effective antibiotic in ambulatory treatment of acute pharyngitis and otitis
      media. It shows a wide range of antibacterial effect comprising most often
      occurring pathogens bringing about acute pharyngitis and otitis media.

PMID- 9757683
TI  - [The use of clarithromycin and amoxycillin in pediatric acute otitis media].
AB  - We presented and compared Clarythromycin and Amoxycillin in the treatment of
      pediatric acute otitis media. We evaluated in 2 groups ther clinical efficacy and
      safety of Clarythromycin versus Amoxycillin.

PMID- 9757684
TI  - [Diagnostic value of rapid streptococcal antigen test provided by Abbott "test
      pack strep A": current report].
AB  - The upper respiratory tract infections are the most frequent infectious diseases
      in human. Beta haemolytic streptococcus group A is the most common etiologic
      factor of bacterial pharyngitis. Delayed or inadequate treatment of streptococcal
      pharyngitis can cause serious subsequent complications. Only a part of patients
      show typical features of the disease so that the diagnosis can be based on
      clinical appearance alone. For this reason we propose direct antigen test as a
      rapid useful method which allows detection of group A streptococci in throat
      swabs. The aim of the study is to estimate clinical value of rapid antigen test
      in differential diagnosis of pharyngitis in children and adults. We have
      performed 50 tests using commercial kit--Abbott Test Pack Strep A. Simultaneously
      conventional bacterial throat cultures were performed. The comparison of results
      acquired by both methods did not revealed any differences.

PMID- 9757685
TI  - [Practical implications of bacterial resistance to antibiotics. Attempts to fight
      it].
AB  - Generation of strains resistant to antibiotics, its genetic mechanisms and the
      role of incompetent administration of these drugs are presented in the paper. The
      resistance is characterised mainly by the generation of extracellular enzymes
      which cause the breakdown of beta-lactam ring Pathogenic bacteria which cause
      changes in the respiratory system are discussed. The use of beta-lactam
      antibiotics with beta-lactam inhibitors is a way to prevent generation of
      resistant strains, the combination of amoxycillin and clavulanic acid is of
      particular importance.

PMID- 9757686
TI  - [Bacterial infections in otolaryngology on clinical material study].
AB  - Bacterial species causing the hospital of the upper respiratory tract and ear
      were analyzed in this study. Authors evaluated differences in the frequency of
      various microorganisms on the clinical material. A special attention is paid to
      the problems of anaerobial species. Microbiological analysis of the isolated
      bacterial species and the assessment of their drugfastness was conducted.

PMID- 9757687
TI  - [Bacterial flora in chronic purulent maxillary sinusitis].
AB  - In the years from 1993 till 1995 there were 132 tests done on occurrence aerobes
      (oxygen bacteria) and 56 tests on occurrence of anaerobes and fungus in patients
      with chronic sinusitis. The most common microorganisms among the aerobes was
      Haemophilus influenzae (23.1%) and Staphylococcus aureus (20.9%). The most common
      microorganisms among the anaerobes was Peptococcus and Peptostreptococcus
      (together 57.1%) and from the strains Bacteroides (36.8). The breeded oxygen
      microorganisms Gr(+) were mostly sensible to clindamycin, cefuroxim and
      augmentin; Gr(-) organisms to amicacin, gentamycin and cefuroxim. Anaerobes were
      mostly sensible to metronidazole and clindamycin.

PMID- 9757688
TI  - [Bacterial flora of the mouth cavity and pharynx and postop wound infection in
      laryngeal cancer treatment].
AB  - The study was carried out on 12 surgically treated patients with carcinoma
      laryngis. Isolation and identification of oral cavity, pharynx, larynx and
      postoperative neck wound microflora were performed. Failures in neck wounds
      healing resulting from bacterial flora were compared. Sources of wound infection
      were found due to biochemical features and antibiotics sensibility.

PMID- 9757689
TI  - [Analysis of bacterial flora of the larynx: analysis of material collected in
      1994-1996].
AB  - This study reveals conclusions which source is analysis of 621 people with the
      pharyngs diseases from 1994 to 1996.

PMID- 9757691
TI  - [The study on biology of bacteriophages and their usage in the treatment of
      bacterial diseases and on the influence of different bacteriophages on cytokine
      production by leukocytes in human peripheral blood].
AB  - The authors showed the examinations of the biology bacteriophages and using them
      in the treatment of the bacteriology infection and influence difference
      bacteriophages in producing cytokinins by leukocytes of human peripheral blood.

PMID- 9757690
TI  - [Case reports of antibiotic complications].
AB  - A case of 30 year old male with the severe course of generalised mycosis after a
      few days antibiotic treatment. The diagnostics and procedure have been
      considered.

PMID- 9757692
TI  - [Rhinomanometry: a method of objective study of nasal patency].
AB  - Rhinomanometry is the most applied method of evaluation of nasal patency in the
      world. In the study the authors present application of rhinomanometry in the
      diagnosis of the nose disease. On own material the authors introduce the
      technique of rhinomanometry and interpretation of its results.

PMID- 9757693
TI  - [Cell response in the nasal mucosa in patients with hay fever during plant pollen
      season].
AB  - The aim of the present study was to determine whether different reactions of the
      nasal mucosa can be a result of a natural provocation with allergen. During the
      pollen season of anemorphilous plants the nasal mucosa may trigger the following
      reactions allergic inflammation or non-specific secretion.

PMID- 9757694
TI  - [The evaluation of cellular immunity in patients with allergy to pollen].
AB  - The study comprised 180 patients with pollinosis, 30 patients with vasomotor
      rhinitis and 30 healthy male adults. The skin reactions of cellular immunity were
      determined by Multitest CMI. The numbers of lymphocytes T and numbers of CD4 and
      CD8 lymphocytes were determined under influence of histamine or clemastinum and
      histamine or cimetidine and histamine. There were statistically significant
      decrease of percentage of CD8 lymphocytes in patients with pollinosis after
      addition of histamine. Statistically significant increase of percentage of CD8
      lymphocytes after the addition of H2 receptor blocker indicated that blocking of
      this receptor neutralized the effect of histamine on the CD8 lymphocytes. Author
      observed increase of Multitest CMI skin reactions (particularly for antigens:
      Streptococcus and Proteus mirabilis).

PMID- 9757695
TI  - [Steroid therapy and surgical treatment of nasal polyps: cytological analysis].
AB  - We have studies influence of steroids applied topically (intranasally) in
      patients with polyps (both operated on and not operated) on the cytology of nasal
      mucosa in conjunction with the level of serum ECP.

PMID- 9757696
TI  - [The role of aeroallergens monitoring in the allergological practice].
AB  - A physician wanting to help his hay fever patient efficiently needs to know the
      causative agent in detail. High qualitative and quantitative variability in
      certain years creates the necessity of constant pollen count monitoring.
      Information on current trends is helpful to doctors in their diagnostic and
      prophylactic procedures as well as in efficient treatment planning.

PMID- 9757697
TI  - [The prophylaxis of allergic rhinitis].
AB  - Authors present their own experience with prophylactic procedures applied in
      allergic rhinitis.

PMID- 9757698
TI  - [Perennial specific immunotherapy in pollen allergy].
AB  - Authors present perennial immunotherapy procedure that they developed with
      sublingal Perosall T 13 and Novo-Helisen Depot. The results of two-year
      observation of 70 patients undergoing above mentioned therapy.

PMID- 9757699
TI  - [The influence of antihistamine agents on reaction time].
AB  - Authors carried out the study of reaction time on auditory stimulus in a group of
      200 patients taking a single dose of: Clemastin, Phenazolinum, Zyrtec, Astemizol,
      Claritin, Disophrol and placebo. The results indicate the prolongation of
      reaction time after the administration of either first or second generation
      antihistaminics.

PMID- 9757700
TI  - [The effects of betahistine on the function of equilibrium system].
AB  - The authors present a pilot investigation of the effect of betahistine on
      vestibular disorders of peripheral and central origin. The evaluation of drug
      efficacy was based on subjective symptoms (vertigo, dizziness) and values of
      nystagmus parameters in ENG. and stability records made during posturographic
      tests, before and after drug administration. The regression or moderation of
      symptoms, such as vertigo and dizziness, was noted as well as the reduction of
      nystagmus slow phase velocity and the amplitude and the reduction of parameters
      during posturographic test. The reduction was observed during the treatment,
      especially during the studies after 4 hours following drug administration. After
      6 months, values of the parameters, especially those made during posturographic
      tests, were close to initial values. The criteria, helpful for diagnosing
      subjective ailments were discussed with the emphasis placed on the significance
      of the processes responsible for equilibrium system function return. The review
      was made of the literature concerning the role of betahistine in the treatment of
      vestibular disorders.

PMID- 9757701
TI  - [Registration of average potentials from neck muscles after the acoustic
      stimulation of the vestibule in patients with impaired function of the internal
      ear and in healthy subjects].
AB  - Electrophysiological studies of human perceptive functions are displayed in last
      years. The vestibular evolved myogenic potentials (VEMP) seems to represent a new
      and promising technique for assessment of vestibulo-spinal reflex function. In
      this study we have measured VEMP in patients with disturbed function of inner
      ear. We have studied 6 patients with unilateral sensorineural deafness and normal
      excitability of vestibular organs; 6 patients with unilateral weakness of
      vestibular function and 19 healthy subjects. We have found that in patients with
      unilateral weakness of estibular function VEMPs had diminished amplitudes whereas
      in patients with unilateral deafness VEMPs were unchanged. These data strongly
      suggest that VEMPs were generated by stimulation of vestibular end-organ. VEMPs
      are highly objective, simple, secure and comfortable technique to assess the
      vestibulo-spinal connections.

PMID- 9757702
TI  - [Modified central otoneurological tests supported by computer analysis].
AB  - The paper presents the results of the study of gaze-evoked nystagmus, direction
      gaze nystagmus and optokinetic nystagmus in 193 subjects, including 85 healthy
      pilots and 64 persons with vestibular pathology of central origin. For this
      purpose, a computer program was applied for evoking strictly standardised
      oculomotor stimuli. Moreover, computer analysis of the responses was introduced.
      To make the method applicable for otoneurological evaluation of flying personnel
      members, physiological norms of the parameters of interest for gaze-evoked and
      optokinetic tests have been presented, based on the study results in different
      age groups. Regardless the applied procedure, an initial analysis was made in
      patients with vestibular pathology of central origin. After having compared these
      results with the results achieved in healthy population, the introduced battery
      of tests was found to be a reliable method of studies for the purpose of
      otoneurological diagnostics.

PMID- 9757703
TI  - [Methods of stimulation of otolithic tract: diagnostic possibilities, critique of
      methods].
AB  - Our modifications of the methods of otolith organs examination were reported. One
      of these methods is eccentric rotation without the support of the body which was
      held in two groups of the persons: control group of 32 healthy persons and 48
      patients with unilateral vestibular loss. The second method of otolith organs
      investigation was evaluation of them by producing dynamic optogravitational
      reactions and measuring an angle of the eyeballs deviation and time of illusion.
      Two groups--one consisting 102 healthy persons and second 91 persons with
      unilateral hearing loss were examined. It was stated that the angle of eyeballs
      deviation was reduced and time of illusion was longer in the group patients in
      comparison with healthy person.

PMID- 9757704
TI  - [The evaluation of the usefulness of electronystagmography studies in Doppler's
      intracranial ultrasonography and brain stem evoked potentials in patients with
      vertigo].
AB  - The aim of the work was the evaluation of correlations between the
      electronystagmographic results examinations and Doppler's intracranial
      ultrasonography and brainstem auditory evoked potentials in patients with
      vertigo. The were 68 patients tested (39 women and 29 men) aged 34-68 years. The
      obtained results showed for the correlations between the electronystagmographic
      results examinations and Doppler's intracranial ultrasonography and brainstem
      auditory evoked potentials.

PMID- 9757705
TI  - [Vertigo and vestibular disorders in patients treated from sudden deafness].
AB  - In the article incidence of the vertigo and vestibular disorders in 119 patients
      with sudden sensorineural deafness was evaluated. It was stated, that vertigo and
      vestibular disorders had 47% of persons, abnormal trace in ENG examination--56%
      of persons. Furthermore hearing recovery was less frequent in group of patients
      with sudden deafness and vertigo than in group of patients without vertigo.

PMID- 9757706
TI  - [Videonystagmography: a new diagnostic method in vertigo].
AB  - We present videonystagmography a new method of vertigo diagnosis. The camera
      record eye movement. We can obtain regostration of nystagmus in all directions.
      Simplicity of use and great sensitiveness of to examinations are very important
      two.

PMID- 9757707
TI  - [A study of the phenomenon of voice intonation: analysis, usage and diagnosis].
AB  - The aim of this work was to study the average rise time (RT) and average flow
      rate (MRT) in utterance. Data were collected from 48 singers and 44 patients. The
      group of patients included cases of modulus vocale, polypus laryngis, paresis
      bilateralis, hemiparesis, and CA laryngis. Various characteristics of utterance
      were recorded synchronously: the frequency and intensity of the fundamental
      laryngeal tone were measured with a laryngophone, a microphone was used to
      monitor acoustic radiation from the mouth, and a pneumotrachometer was applied
      for the measurement of flow rate. The data were stored and analysed with the use
      of a computer. Results show that the analysis carried out in the study describes
      the distinctive characteristics of normal and pathologic utterance. The main
      findings are as follows: a) rise time (RT) decreases with increasing loudness and
      pitch of the sound and is also shorter in staccato than inlegato sounds; b)
      during the initial transient of staccato sounds, the average flow rate in the
      glottis increases with intensity and pitch of the sound; c) pre-fonation time
      (TPP) and air volume do not differentiate normal and pathologic utterance; d) in
      cases of voice pathology, the analysis of utterance described in this study can
      be used for the evaluation of therapy and rehabilitation.

PMID- 9757709
TI  - [Extrameatal myringoplasty in the treatment of tympanic membrane perforations].
AB  - The clinical analysis of the patients after tympanic membrane reconstruction with
      the temporal muscle fascia has been conducted. The total number of 145 patients,
      operated at the Otosurgery Department Medical University of Lodz, was divided
      into 2 Groups. Group 1 (n = 75) patients with chronic otitis media (central
      perforation and mobile ossicular chain). The preoperative mean conductive hearing
      deficit of 20 dB was observed in all evaluated patients. After surgery a
      satisfactory hearing improvement was observed in 90% of the patients. Group 2 (n
      = 70) patients with the reconstructed postero-superior part of the tympanic
      membrance and if necessary external auditory canal wall reconstruction. The mean
      conductive hearing deficit of up to 30 dB was observed before the surgery.
      Postoperatively in 75% of patients the hearing improvement was observed as well
      as the satisfactory healing of fascia implant. The postoperative evaluation
      indicates a better hearing improvement after the myringoplasties with the
      prefascial lamina than in the myringoplasties performed in the traditional ways.

PMID- 9757708
TI  - [Audiological diagnosis in Military Medical Academy in Warsaw].
AB  - Basis clinical proceeders in hearing loss diagnosis and the instruments used in
      the Department of Otolaryngology of the Military Medical Academy in Warsaw were
      presented.

PMID- 9757710
TI  - [A case of objective tinnitus].
AB  - The authors presented a case of objective tinnitus in patient with glomus tumor
      suspicion. Tinnitus epidemiology, classification, causes and diagnostic procedure
      were described. Any organic alterations, which would cause tinnitus, did not
      find.

PMID- 9757711
TI  - [Treatment results of acoustic trauma].
AB  - 20 patients aged from 18 to 42 treated in the past few years because of acoustic
      trauma. Together the investigations concerned 24 years. Therapeutic schema
      comprised intravenous infusion--Sermion (Nicergoline--amp. a 4 mg) or Cavinton
      (Vinpocetine--amp. a 10 mg) 1 amp.--twice a day for 10 days. The treatment of 60%
      of the patients started in the first week after the trauma occurred, of 20% in
      the second week and the remaining 20% later on after 15 days when the trauma took
      place. The obtained results of treatment both of improvement of hearing (79.2%)
      and tinnitus (66.6%), support the necessity of treatment of acoustic trauma
      independently from the time that passed after trauma had occurred. Better results
      of audiometric improvement of hearing (54.2%) and tinnitus disappearance (50%)
      were obtained in the patients whose treatment started in the first week after
      trauma. The improvement of hearing and tinnitus disappearance was more observed
      in patients after treatment by using Sermion than Cavinton.

PMID- 9757712
TI  - [A prognostic value of of stapedius reflex and accommodation coefficient in
      patients with Bell's palsy].
AB  - At 25 patients with Bell's palsy every 7 days stapedius reflex (SR),
      accommodation coefficient as well as improvement of mimical facial movements were
      examined. At 5 patients SR was noticed before treatment, at 13 after 14 days, at
      4 after 21 and at 3 after 28 days since disease beginning. There was significant
      correlation between return SR and improvement of mimical facial movements, but
      there wasn't correlation between SR and accommodation coefficient.

PMID- 9757713
TI  - [Results of surgical treatment of impaired nasal patency evaluated by
      rhinomanometry and self-assessment by patients].
AB  - 20 patients suffering from nasal potency disturbances were carefully clinically
      (including self-assessment) and rhinomanometrically evaluated before and after
      surgical treatment. Surgery brought sufficient improvement in nasal potency and
      long term relief in clinical symptoms in most of the patients. Cases with only
      temporal release were strictly analysed. We would like to emphasize the
      importance to employ both surgery and accompanying conservative treatment to cure
      these patients with significant functional contribution.

PMID- 9757715
TI  - [Clinical application of magnetic pulsing fields in paranasal sinusitis
      treatment].
AB  - In this work were described advantages of the pulsating magnetic fields in
      sinusitis treatment as independent and helping method.

PMID- 9757714
TI  - [Pathological changes of frontal sinus in the materials of the Otolaryngological
      Clinic of Medical Academy in Lodz (1986-1996)].
AB  - Authors report 25 cases of frontal sinus diseases treated surgically at the ENT
      Department Medical University of Lodz. There were three groups of pathologies: 13
      cases of inflammatory disease, 9 osteoma cases and 3 trauma cases. The total
      number of 30 surgical procedures has been performed (13 Beck's method, 6 radical
      method, 6 classical method, 2 Ogston-Luc method and 3 reconstructions of anterior
      wall of the frontal sinus using bone sutures). In each group the type of surgical
      method and the causes of the possible postoperative pitfalls and recurrence of
      the disease were analyzed.

PMID- 9757716
TI  - [On keratomas on the frontal sinus].
AB  - Etiopathogenesis of the frontal sinus kertomas has been discussed paying a
      special attention to the frequency of its occurrence reported in literature.
      Authors present a rare complication of frontal sinus keratoma involving a bone
      destruction of nearby lying structures.

PMID- 9757717
TI  - [A case of post-traumatic nasal hemorrhage stopped by externa carotid artery
      ligation].
AB  - A case of severe posttraumal epistaxis treated by external carotid artery
      ligation is reported. This surgical procedure seems to be relatively simple and
      highly effective in the management of refractory epistaxis.

PMID- 9757718
TI  - [Clinical evaluation of Olbas oil effect on nasal mucosa in acute rhinitis
      patients during common cold].
AB  - The aim of the study was the clinical evaluation of the effect of Olbas oil on
      nasal mucosa in patients with acute rhinitis during common cold. 15 patients with
      2-3 days history of acute rhinitis during common cold, both sexes, in the age
      between 23-47 were investigated. All the examinations were done before using,
      after the first inhalation, and after 7 days of Olbas oil administration. The
      investigation before using Olbas oil was comprised of: history data, general and
      otorhinolaryngological examination with particular evaluation of nasal mucosa,
      anterior rhinomanometry, saccharin translocation time, olfactometry,
      microbiological cultures, histamine nasal provocation test. At the end, after 7
      days of Olbas oil inhalation 3 times a day for 4 minutes 4 drops of Olbas oil
      applied into a handkerchief, all the test were done again, as at the beginning.
      The study showed a good of the effect of Olbas oil on nasal mucosa in patients
      with acute rhinitis during common cold.

PMID- 9757719
TI  - [The usage of nasal drops Tyzine in otorhinolaryngology].
AB  - In this research the authors presented their experiences in the treatment of non
      complicated and complicated acute mucous membranous rhinitis with application of
      shrinking nasal drops Tyzine as a locally affective remedy assisting the therapy.
      The aim of this research was the estimation of the efficiency of Tyzine drops
      with mucous membranous rhinitis, their effect on the efficiency of the ciliary
      transport and stating the probable side effects occurring after their
      application. 80 persons were observed--60 adults who were treated with 0.1%
      solution oftetrazoline hydrochloride and 20 children who were given 0.05%
      solution. To state the condition of the ciliary transport within mucous membrane,
      a saccharine test was conducted with all examined persons on the 1st and 5th-7th
      days of treatment and on the 21st day after completing the therapy. The results
      of the observation seem to be positive as for as the efficiency of nasal drops
      Tyzine under the stipulation that the drops are reasonably applied and according
      to the doctor's recommendation.

PMID- 9757720
TI  - [Selected immunological studies of chronic purulent and hypertrophic
      otolaryngological diseases].
AB  - The aim of this work was the comparison of selected immunological parameters in
      patients with chronic purulent and hypertrophic otorhinolaryngological diseases
      who were to be operated on. The patients were divided into two groups: 1-31
      patients aged 17-58 with chronic purulent otorhinolaryngological diseases. The
      following immunological parameters were carried out: rheumatoid factor (RF),
      immunoglobulins IgG, IgM, IgA, proteinogram including the level of albumin,
      globulin alpha1, alpha2, beta and gamma. In chronic purulent
      otorhinolaryngological diseases the characteristic features are the reduction of
      the level of globulin alpha1 (67.7%) and gamma (35.5%), while in hypertrophic
      cases globulin alpha1, and beta--91.7% each.

PMID- 9757721
TI  - [A case of mucous cyst of the nasopharynx].
AB  - We presented a rare case mucocele cyst of the nasopharynx in a 41 year old man.
      The cyst was located at the higher level between the roof and right lateral band
      of nasopharynx, and was removed by the transpalatal approach.

PMID- 9757722
TI  - [Oxidase activity in patients with laryngeal carcinoma treated by radiotherapy].
AB  - According to Ravin's method an oxidative activity of ceruloplasmin was determined
      in the group of patients with carcinoma of larynx before and after rtg-therapy
      and at the control group of healthy individuals. As a result of this assay the
      significantly increased of oxidative activity ceruloplasmin was obtained in the
      individuals with the carcinoma of the larynx before rtg-therapy in comparison to
      the group of healthy subjects. Simultaneously a significant decrease of the
      oxidative activity of serum ceruloplasmin in the individuals with carcinoma of
      the larynx after rtg-therapy was observed.

PMID- 9757723
TI  - [Trauma of the larynx and a method of treatment: case report].
AB  - The authors presented the case of trauma of larynx after explosion of bullet. The
      patient was treatment by use the special "T" tracheal cannula. That cannula fixed
      the larynx supported free passage of superior respiratory tract and led to good
      result of treatment.

PMID- 9757724
TI  - [Endoscopic examination of esophagus performed by an otolaryngological head and
      neck surgeon].
AB  - The authors have analyzed 562 cases treated by esophagoscopy in ENT Department of
      District Hospital Nr 1 in Rzeszow, Poland from 1987 to 1996. There have been 580
      esophagoscopy performed during this period: In this number 504 therapeutic
      procedures and 76 diagnostic ones. The most common indication for therapeutic
      esophagoscopy has been the suspection or presence of foreign body in the
      esophagus and rarely other pathology of upper part of digestive tract.
      Complications of esophagoscopy are rather rare and in the most cases they are the
      result of perforation of esophageal wall during esophagoscopy. In presented
      material the complication rate was 0.17%. Impacted parts of false teeth in
      esophagus should be always removed by experienced otolaryngologist under
      endotracheal anesthesia and with esophageal muscles relaxation.

PMID- 9757725
TI  - [The danger of removing some esophageal foreign bodies by fiber optics].
AB  - The authors presented 4 cases of patients with a foreign body in the esophagus,
      which has been tried to remove by means of fiberoscopy and rigid esophagoscopy.
      The fiberoptic endoscopy has failed either as a diagnostic method or as a
      therapeutic one. The classical esophagoscopy has turned out to be much better in
      both cases. The fiberoscopy is a valuable diagnostic and therapeutic procedure in
      a lot of diseases of digestive tract. Especially it is useful in order to remove
      some foreign bodies from the esophagus, but at the same time it fails when
      removing big foreign bodies (e.g. parts of false teeth, large bones). In these
      cases rigid esophagoscopy is the only effective method when performed under
      endotracheal anesthesia and with esophageal muscles relaxation.

PMID- 9757727
TI  - [The evaluation of granulocyte function before and after surgical treatment in
      patients with chronic inflammation of the middle ear and palatine tonsils].
AB  - The aim examinations was the evaluation of granulocytes (PMNL) pre- and
      postsurgical treatment in patients with chronic inflammation of middle ear and
      palatine tonsils. The examined 40 persons and divided into three groups: I--18
      patients with chronic inflammation of middle ear, II--10 ones with chronic
      tonsillitis and III--12 healthy persons. There were evaluated: "in vivo" and "in
      vitro" migration, bactericidal index and absorption of S. aureus labeled 14C
      isotope (phagocytic index) in the own modification. Preoperative treatment in
      patients with chronic inflammation of middle ear and palatine tonsils in
      comparison to the healthy were noticed: characteristic increase of the migration
      area, the MIF liberation and the phagocytic index, decrease in the bactericidal
      index (but more in group II). After a year postsurgical treatment the function of
      granulocytes in patients of group II was more similar to the healthy than in
      group I.

PMID- 9757726
TI  - [The case of purulent epiglottitis complicated by the cervical and mediastinum
      phlegmon with septic shock].
AB  - The authors showed the case of purulent epiglotitis complicated the neck and
      mediastine phlegmone with septic shock.

PMID- 9757728
TI  - [Clinical studies of Olbas oil tolerance and its effect on nasal mucosa in
      healthy volunteers].
AB  - The aim of the study was the clinical examinations of the tolerance and effect of
      Olbas oil on nasal mucosa in healthy volunteers during permanent 4 weeks
      administration. 23 healthy volunteers both sexes in the age between 20-50 were
      investigated. This investigations consisted of: history data, general and
      otorhinolaryngological examination, with particular evaluation of nasal mucosa,
      anterior rhinomanometry, olfactometry, saccharin translocation time,
      microbiological cultures, histamine nasal provocation test. Besides, each patient
      has follow up self evaluating chart of symptoms and adverse effect from the eyes,
      nose, pharynx and others. All the examined persons showed a very good tolerance
      of Olbas oil after 28 days of inhalation.

PMID- 9757729
TI  - Female genital mutilation: some ethical questions.
AB  - This paper provides some basic information about female genital mutilation (FGM)
      as a social problem and as a health problem. It includes selected actions taken
      over the last 45 years by the United Nations regarding FGM. The focus here is on
      the ethics of individuals and institutions, such as the World Health
      Organization, attempting to intervene in traditional cultural practices like FGM.
      This discussion raises some questions about ethical universals and ethical
      relativism with regards to FGM and the attempts to change or eradicate this
      practice.

PMID- 9757730
TI  - Hobson's choice: reproductive choices for women with learning disabilities.
AB  - This paper examines the present law in England and Wales concerning the
      sterilisation of women who are unable to give valid consent to medical treatment.
      In particular, it considers why sterilisation is frequently presented as the only
      meaningful reproductive choice that can be made by or on behalf of women with
      learning disabilities. In addition, the paper assesses the extent to which the
      best interests test, as formulated by the English courts, has been successful in
      the promotion of dignity and autonomy of women with learning disabilities. It is
      submitted that some of the issues presented to the courts have not received
      adequate consideration and others have been considered which are not relevant to
      the determination of the best interests of these patients. Furthermore, the best
      interests of the adult patient are determined by reference to the 'Bolam' test.
      This paper questions whether the Bolam test is the appropriate mechanism for
      determining the patient's best interests, having particular regard to the
      Australian model of decision-making for the intellectually impaired.

PMID- 9757731
TI  - Contracting and the purchaser-provider split in western Europe a legal
      organizational analysis.
AB  - Market forces have been introduced in the health care systems of many European
      countries. Fundamental to the introduction of the market was the need to
      distinguish between the roles of purchaser and provider. In this article the
      authors have analyzed the consequences of contracting and the purchaser-provider
      split from both a legal and organizational perspective. Using a modification of
      an existing theoretical framework for analyzing the basic health care models,
      contracting and the purchaser-provider split in some Western European countries
      has been analyzed. Including the legal and organizational dimension into these
      economically oriented models, these models can also be used for analyzing recent
      trends and developments. A four-country analysis indicates trends towards
      convergence of health care systems and both decentralization and integration in
      the systems. The future roles of both managers and lawyers working in health care
      need to be further defined.

PMID- 9757732
TI  - Islamic jurisprudence and the end of human life.
AB  - Death is an inevitable reality but the causes leading to death may vary from
      individual to individual. In the past, death was considered to be a simple and
      straightforward phenomenon. The general practitioner would issue the death
      certificate once he was convinced that there was cessation or absence of
      spontaneous life in the patient. This meant that the patient had stopped
      breathing, his heart had stopped beating, there was unresponsiveness, his body
      had turned cold and finally rigor mortis had set in. With the successful
      accomplishment of heart transplants, it became obvious that a process of
      rethinking on how death could be determined had to be instituted. Cessation of
      heartbeat is no longer considered evidence of death since the heart is now able
      to be substituted with that of a just-deceased donor or with that of a baboon or
      even with a mechanical one. Moreover, modern biomedical innovations like the
      resuscitator and cardiac pacemaker have made it imperative to establish a set of
      criteria by which the moment of death could be identified. Diagnosis of brainstem
      death is relevant to the issue of retrieving viable vital organs, i.e. heart,
      lung, liver and kidney, for transplantation purposes. The Holy Qur'an emphasizes
      the universality of death and from its teachings one gathers that the moment of
      death would be at the time when the soul is separated from the body. However, one
      has to concede that the Qur'an does not in any way tell us anything about the
      nature of the soul nor of its location in the human body, hence the dilemma of
      Muslims insofar as brain death is concerned. In this paper, an attempt is made to
      analyse the deliberations of the classical and contemporary Muslim scholars on
      the end of human life with the aim of determining whether brain stem death could
      in effect be regarded by Muslims as the end of human life and if not why?

PMID- 9757733
TI  - HIV/AIDS and human rights in prison. The Costa Rican experience.
AB  - HIV and AIDS issues deal directly with Human Rights and Public Health. Four basic
      principles have been acknowledged internationally in connection with HIV/AIDS:
      Autonomy, confidentiality, right to health and non-discrimination. According to
      these principles, it is not possible to adopt illegal or unethical measures
      toward HIV- infected persons. However, these may rarely be necessary in the case
      of prisoners, taking into account the possibilities of unpredictable behavior,
      violence and use of drugs, which are common in prisons. The World Health
      Organization as well as the United Nations have established the possibility of
      taking measures, different from those outside the jail, that may be illegal but
      necessary in order to protect the human rights of inmates, the general prison
      population and the security of the penitentiary system. Therefore coercive
      measures such as isolation may be imposed upon an inmate infected by HIV when he
      or she deliberately may try to infect others. This paper examines different types
      of situations dealing with HIV/AIDS in prison and reviews the international
      recommendations and the way the Costa Rican legal and penitentiary system have
      adopted them in accordance with its legal system and national prison
      characteristics.

PMID- 9757734
TI  - Protection of patients' rights in Estonia.

PMID- 9757736
TI  - Evaluation of the new legislation on psychiatric compulsory care in Sweden.
AB  - In 1992 the Compulsory Mental Act from 1966 was replaced by two enactments. The
      purpose was to restrict the use of compulsory care and coersive measures, to
      strengthen the legal safeguards for the patients, and to increase the protection
      of society. A follow-up and evaluation of the reform has been performed by the
      National Board. This paper will present details of the results. The main
      impression was that the laws function fairly well. However, the National Board
      proposed some changes in the new acts. The government has started a parliamentary
      group to consider these suggestions.

PMID- 9757735
TI  - Brain trauma: cause-consequence connection problems.
AB  - Despite sophisticated equipment like computerized tomography, in some cases
      doctors have a problem with the diagnostic procedure in relation to patients with
      serious injuries of the central nervous system (CNS). There may be no clinical
      signs of disorders of the CNS, or other evidence of difficulties, but diffuse
      axonal lesions and demyelinisation processes often exist. This type of lesion is
      a special pathomorphological entity, known as the syndrome of patient who talks
      and dies. Macroscopical and microscopical findings are poor and rare, especially
      in the hours immediately following the injury. The main findings are not
      evidential and the problem is the explanation of sudden death from unknown
      causes. The following studies are based on human tissue analyses. They are based
      on the analyses of the CNS of patients who suffered from brain trauma. The
      specimens from the brain stem were taken in order to perform histological,
      microscopic analysis. Percentage value of surface of myelin for the control group
      was X1 38.62% for HE technique and X1 33.46% for Gomory's method. The value for
      the test group was X2 16.12% for HE technique and X2 13% for Gomory's technique.
      Statistical probability for both groups was 95% (P < 0.05; T = 14.9). Application
      of these procedures helps legal authorities to make trials more objective.

PMID- 9757737
TI  - Medical negligence and post traumatic stress disorder (PTSD).
AB  - Post traumatic stress disorder (PTSD) is well recognised as a consequence of
      natural and man-made disasters, accidents and assaults. An increasing number of
      plaintiffs making claims for compensation alleging medical negligence complain of
      the symptoms of PTSD. Medical accidents such as anaesthetic awareness and
      stillbirths may be claimed as stressors and relatives may allege PTSD as a
      psychological injury following witnessing the death or suffering of a loved one.
      A series of cases will be presented. Many cases are entirely genuine but
      increasing media publicity has alerted potential plaintiffs and their legal
      advisers to the symptoms of PTSD which make evaluation of symptoms difficult for
      psychiatric experts. Psychometric tests exist to screen PTSD but research has
      shown that they can be falsified and it would be unwise to rely on such tests.

PMID- 9757738
TI  - A study of substance abuse on two campuses of University of Papua New Guinea.
AB  - BACKGROUND: Recent research reports indicate that there is a substantial amount
      of substance abuse on the campuses of the University of Papua New Guinea.
      OBJECTIVE: To compare the frequency and quantity of alcohol and drug abuse on the
      two campuses of the University of Papua New Guinea in the National Capital
      District. METHODS: A purposely designed questionnaire was used to collect data
      randomly on a total of 90 subjects (45 from each campus). The data was subjected
      to computer analysis. RESULTS: The results show that abuse of alcohol, tobacco
      and other drugs is prevalent on the two campuses of the University of Papua New
      Guinea. CONCLUSION: The results will form the basis of recommendations for
      substance abuse prevention, through information and education of the University
      students and staff members.

PMID- 9757739
TI  - Informed consent to medical treatment--the Israeli experience.
AB  - The ideological foundation of the doctrine of "informed consent" is rooted in the
      concept of personal freedom and freedom of choice. The concept of individual
      autonomy is represented by the "reasonable patient" standard which requires the
      disclosure of all information which a reasonable person in the position of the
      patient would need in order to make a rational decision regarding a proposed
      medical treatment. This attitude, however, conflicts with the traditional
      paternalism which is reflected in the "reasonable physician" standard, that is
      that a doctor must disclose that medical information which a rational doctor
      would relate to a patient in order to receive his consent. The enactment of the
      Patients' Rights Law in Israel in 1996 was an essential turning point in Israeli
      medical law. Section 13 of the new law explicitly establishes the requirement of
      informed consent and the details which a doctor must relate to a patient in order
      to reach the said agreement. Nevertheless, the law does not state the standard
      according to which it should be assessed whether the disclosure was proper. In a
      recent decision (C.A. 434/94 Shai Berman et al. v. Mor--the Institute for Medical
      Information, Ltd.) the Israeli Supreme Court took a step forward and determined
      that the duty to inform a patient will be judged by recognised criteria of
      negligence as they apply to the merits of each case.

PMID- 9757740
TI  - Video technology and children's evidence: international perspectives and recent
      research.
AB  - Research has shown that children can be as competent and reliable as adults as
      eyewitnesses of crime, if questioned in an appropriate manner. However, there is
      considerable variation between, and within, countries in the way in which child
      witness evidence is accepted in criminal cases. This article reviews the legal
      facilities that exist for young witnesses in countries such as the United States,
      England & Wales, Canada and Australia. Particular emphasis is placed on recent
      research into the use of video technology by the courts in child abuse cases-
      namely testimony with a live video link or a pre-recorded interview in place of
      live, open court evidence. Studies into the use of live link and videotaped
      interviews have shown that these innovations could help to reduce the trauma of
      testifying for children and could lead to better quality evidence from the child.
      However, there is considerable concern among legal and child protection
      professionals about the relative lack of impact of video testimony when compared
      with live, in-court testimony. Research has uncovered significant support among
      legal professionals towards using curtained partitions 'screens' to allow a child
      witness to testify within the courtroom without allowing the child to see, or be
      distracted by, the accused. There is also widespread concern about the
      questioning techniques used in videotaped interviews and with the live link.
      Future implications for the use of video testimony are also discussed.

PMID- 9757741
TI  - Forensic medicine, its tasks and duties in medical malpractice and medico-legal
      litigation.
AB  - Forensic medicine assists in clarification of cases of violent death, assessment
      of bodily damage and indemnity, especially in cases of work injuries, it also
      deals with deaths that occur within two hours of a doctor's intervention. As
      "legal medicine", forensic medicine is taught both to medical students and to
      students of the juridical faculties. In cases of medical malpractice, forensic
      pathologists give opinions in courts. Cases of alleged malpractice are handled
      differently in different countries. Establishment of expert committees in the
      Czech Republic represents a reasonable solution to this problem. Activities of
      the committees are described.

PMID- 9757742
TI  - Medical research and informational privacy.
AB  - This paper focuses on the processing of medical data for scientific research and
      the protection of privacy. Attention will be given to the collection, storage and
      use of medical data for research. First, the international framework, as provided
      by the Council of Europe's Convention for the protection of individuals with
      regard to automatic processing of personal data--and Recommendation No. R (83) 10
      on the protection of personal data used for scientific research and statistics,
      and Draft Recommendation on the protection of medical data, based on this
      Convention--and the European Directive on the protection of individuals with
      regard to the processing of personal data and on the free movement of such data,
      will be described in broad outlines. Within this international context, the
      relevant Dutch laws, that is to say the Law on Registration of Personal Data and
      the Medical Contract Act, will be discussed. The paper concludes with some
      remarks on the (Dutch) Code of Conduct on Health Care Research.

PMID- 9757743
TI  - Money, medicine, and Methuselah.

PMID- 9757744
TI  - New concepts in the pathogenesis and treatment of allergic asthma.
AB  - This review delineates the currently accepted, multifaceted approach to the care
      of an asthmatic patient. Therapy is based on our improved understanding of the
      pathophysiology of this complex disease, in which IgE and mediators derived from
      many cells contribute to airway inflammation. The latest trends in therapy
      involve the institution of anti-inflammatory medications relatively early in
      disease. With the recent availability of a novel class of therapies, the
      leukotriene antagonists, and other therapies based on antagonism of adhesion
      molecules, cytokines, chemokines, or IgE itself, the future may provide
      additional alternatives for the physician treating patients with asthma.

PMID- 9757745
TI  - Current events and bioethical concerns in physician-assisted death.
AB  - In June 1997, the Supreme Court of the United States found that the Constitution
      does not guarantee a right to physician-assisted suicide, thereby allowing states
      the opportunity to variously prohibit or permit such practice. The Court's
      findings notwithstanding, physician-assisted death remains a topic of intense
      medical, legal and philosophical discussion. Principled discourse variously
      supports both an ethical prohibition against assisted death and an ethical
      obligation to help some patients achieve death. Both theoretical and practical
      concerns are raised by the practice of physician-assisted death. This essay
      reviews recent events and developments concerning assisted suicide and
      euthanasia. The discussion which follows was generated by the members of the
      Committee on Bioethical Issues of the Medical Society of the State of New York
      and builds upon a previous Committee report.

PMID- 9757746
TI  - Anesthesia for nonobstetric surgery during pregnancy.
AB  - Approximately 50,000 pregnant women undergo nonobstetric surgery each year in the
      United States. Administering anesthesia during such surgery is one of the only
      situations in which anesthesia impacts on more than one individual (mother and
      fetus) at the same time. Providing a safe anesthetic to the pregnant woman
      requires an understanding of the physiologic changes of pregnancy and the impact
      of anesthesia and surgery on the developing fetus. The following review will
      consider the risks of the mother and to the fetus during nonobstetric surgery.

PMID- 9757747
TI  - Concepts of preemptive analgesia for postoperative pain.
AB  - BACKGROUND: The predictable relationship between surgical injury responses and
      the ensuring postoperative pain has led to the development of the concept of
      preemptive analgesia, with its potential to improve the quality of the
      postoperative period. METHODS: A review of publications concerning the studies of
      the physiology of pain and the development of clinical strategies toward the
      prevention of postoperative pain was undertaken. RESULTS: Clinical studies using
      various methodologies indicate that preemptive analgesia may, in some
      circumstances, attenuate postoperative pain. Unfortunately, these studies were
      not always reproducible. Preemptive analgesia in these studies failed to prevent
      or attenuate postoperative pain. CONCLUSION: Techniques directed toward reducing
      and/or eliminating postoperative pain are still being developed, and their
      clinical utility is yet to be fully evaluated.

PMID- 9757748
TI  - Multiple cerebral infarction in Japanese breath-hold divers: two case reports.
AB  - We report on two Japanese breath-hold divers (ama) who developed neurological
      disturbances following more than 3 hours of consecutive dives to 15-25 meters of
      seawater. Their magnetic resonance images of the brain showed multiple cerebral
      infarcts which were consistent with their neurological symptoms. The cerebral
      lesions seem to have been caused by repetitive breath-hold dives for extended
      periods of time. Immediate recompression is required when neurological symptoms
      develop after such dives.

PMID- 9757750
TI  - Complications of subcutaneous injection ports.
AB  - Subcutaneous injection ports have become widely used for patients who require
      prolonged central venous access. Complications of their placement and use are
      well documented in the existing literature. We report two previously undocumented
      complications occurring in Port-a-Cath units, and suggest methods to lessen the
      likelihood of recurrence of these problems.

PMID- 9757749
TI  - Severe hyponatremia, neuroleptic malignant syndrome, rhabdomyolysis and acute
      renal failure: a case report.
AB  - Acute renal failure secondary to myoglobinuria is a rare yet possible
      complication of malignant neuroleptic syndrome associated with the use of
      dopamine antagonists. We describe the case of a 42-year-old schizophrenic man who
      presented with severe hyponatremia, and proceeded to acute malignant neuroleptic
      syndrome, rhabdomyolysis, and acute renal failure. We contend that the acute
      hyponatremia may have served as a precipitating factor.

PMID- 9757751
TI  - Gynandroblastoma in pregnancy: case report and review of literature.
AB  - Gynandroblastoma is an extremely rare tumor, composed of sex cord and stromal
      cells of both ovarian (granulosa-theca) and testicular (Sertoli-Leydig) types. We
      believe that its occurrence during pregnancy has not been previously reported.
      The patient was a 32-year-old woman who during her pregnancy was noted to have a
      progressively enlarging, unilocular left ovarian cyst. Beginning at 18 weeks
      gestation, the fetus required multiple platelet transfusions for severe
      alloimmune thrombocytopenia. A viable baby girl was delivered by cesarean section
      at 39 weeks gestation. At that time, an ovarian cystectomy also was performed.
      When the histology of the tissue subsequently became known, a left salpingo
      oophorectomy was performed for gynandroblastoma. One year later, at the time of
      laparoscopic sterilization, the examination of the pelvis was normal.

PMID- 9757753
TI  - The Libby Zion case revisited: what have we learned?

PMID- 9757752
TI  - Impact of the Libby Zion case on graduate medical education in internal medicine.
AB  - Residency training in New York State was substantially altered by the Libby Zion
      case. Work-hour limitations and augmented supervisory requirements changed the
      patterns of training--particularly in internal medicine--but with uncertain
      impacts on the quality of education and patient care. In this historical
      analysis, we review another major effect of the case: a substantial augmentation
      of the number of trainees. The need to maintain adequate inpatient staffing-
      within the ground rules of the Residency Review Committee, and in consideration
      of the reimbursement formulae and financial climate of New York State--conspired
      to promote substantial residency program expansion. Similar forces contributed to
      a national trend to increase the number of trainees. The history, cost and impact
      of these personnel changes are reviewed.

PMID- 9757754
TI  - Unexpected factors predict control of hypertension in a hospital-based homeless
      clinic.
AB  - BACKGROUND: Boston Health Care for the Homeless Program (BHCHP) physicians
      conduct a primary care clinic twice a week at Massachusetts General Hospital
      (MGH). The MGH clinic is part of a city-wide network of BHCHP clinics providing
      primary care services to indigent patients. Despite this network, long term
      control of chronic illnesses such as hypertension (HTN) continues to challenge
      the clinic staff. METHODS: In an effort to better understand the factors
      obstructing long term treatment of chronic illness, we conducted a chart review
      of hypertensive patients seen over a three-year period (January 1991 to March
      1994) at the MGH clinic. Frequency of visits, total number of visits and
      physicians' notes on concomitant diagnoses were analyzed for their correlation to
      control of hypertension. RESULTS: Overall control of hypertension was poor (42%).
      A greater proportion of patients with a diagnosis of psychiatric illness
      responded to treatment intended to lower their blood pressure below 140/90 mm Hg
      than those without such a diagnosis (odds ratio: 10.2). While there was no
      difference in the total number of clinic visits during the study period, those
      with a diagnosis of psychiatric illness had a lower average number of days
      between their first and third visits (52 days vs 108 p = 0.002). CONCLUSIONS: A
      greater proportion of patients with concomitant psychiatric diagnoses exhibited
      blood pressures < or = 140/90 mm Hg than patients without mental illness. The
      increased frequency of visits at the onset of treatment may confer a positive
      effect on long term control of HTN among homeless patients attending outpatient
      hospital-based clinics.

PMID- 9757755
TI  - Generalized morphea.

PMID- 9757756
TI  - [Construction and its characteristic on the concept of a 'health culture'].
AB  - Toward the 21st century, subjects and methods of hygiene and public health will
      be specialized and subdivided. However, practical approaches to human health need
      an integrated method focusing to a structure of human life. Under these
      circumstances, the concept of 'health culture' becomes prevalent. The role of
      hygiene related to the improvement of life style, the development of re-cycle
      system, and fulfillment of a barrier-free system focussed on the handicapped and
      the elderly have become increasingly important. Therefore, an increase in the
      recognition to the concept of 'health culture' is essential to the research of
      hygiene. The purpose of this paper is to make a historical and theoretical
      analysis of health culture', in order to promote it as the leading concept of all
      activities concerned with health in the 21st century. The methods of this paper
      are mainly historical and theoretical review. 'Health culture' was introduced in
      American and European societies a hundred years ago. Health culture in the USA
      involves knowledge and skills applied to actual daily life, refrecting pragmatism
      as the ideal feature of American society. In Germany, the concept of 'Hygienishe
      Kultur' was established at the field of social hygiene by Grotjahn and by Fischer
      in the early 20th century. This concept recognized the importance of the
      development of culture and independence of life in labour based on the evolution
      of the concept of 'Hygienishe Kultur'. In Japan, under the influence of German
      social hygiene, the social hygienic theory flourished. A social hygienist, Tetsuo
      Hoshino used the term 'hygienic culture' in the context of life creation toward a
      healthy life. Health culture is the total system concerning knowledge,
      experience, skill, and norms related to health, which has developed with the
      development of society. It has fundamental function promotes the creation of
      culture and self-cultivation of living man, whereas, it contributes to the
      realization of health based on individuality, in conjunction with the co
      operation of medical and health sciences. The contemporary representation of
      health culture includes new health care activities such as self-care, a self-help
      movement, and health volunteer activities. It means the basic shift of the
      function of health culture is from that of life style to life movement. Nowadays,
      the role of hygiene in the total health care system is seriously considered. The
      goal, objects, and methods of hygiene should be re-evaluated under the concept of
      'health culture', in order to re-define hygiene as the science for people living
      in a society.

PMID- 9757757
TI  - [The relationship between stress and health indicators in an urban population-
      from a study of subjects selected by sex and age groups who underwent health
      check-ups in S city in Osaka Prefecture].
AB  - Many people in recent years are living under conditions involving various kinds
      of major and minor stress. This study was done to analyze how an urban population
      experience stress in daily life and to establish any relationship between the
      feeling of stress and people's daily habits or health conditions. The subjects
      were 2,234 residents, who availed themselves of general health check-ups in a
      city in Osaka Prefecture in 1992. The main results were as follows: 1) We
      designed and assessed a total stress score for causes of stress in daily life and
      a total depression score for the depression condition of subjects. 2) The
      proportion of subjects who showed a high total stress score decreased with age.
      The proportion of subjects who showed the highest total stress score was the
      largest in the age group of 40-49 years for men and of 30-39 years for women. 3)
      The proportion of subjects who had short working hours, much leisure time
      available, and low total depression score and complained much about health
      conditions increased with age. The proportion of subjects who had the longest
      working hours was the largest in the age group of 30-39, that of those who had
      little leisure time available and showed the highest total depression score was
      the largest in the age group of 40-49, and that of those who complained most
      about health conditions was the largest in the age group of 60-69 for men. The
      proportion of subjects who had the shortest sleeping hours and the longest
      working hours was the largest in the age group of 40-49, that of those who had
      little leisure time was the largest in the age group of 30-39, and that of those
      who showed the highest total depression score was the largest in the age group of
      30-39 and 50-59 for women. 4) The total stress score showed significant
      relationships with the amount of leisure time available, the degree of complaints
      about health condition, and the total depression score for men and with sleeping
      hours, the amount of leisure time available, the degree of complaints about
      health condition and the total depression score for women. 5) The total stress
      score showed a significant correlation with high blood pressure for men and
      women. 6) The amount of leisure time available showed significant relationships
      with sleeping hours for men and working hours for men and women. The total
      depression score showed significant relationships with the degree of complaints
      of health condition for men and with sleeping and working hours, the amount of
      leisure time available and the degree of complaints of health condition for
      women.

PMID- 9757758
TI  - [Flow cytometric analysis of the effects of 50 Hz magnetic fields on mouse
      spermatogenesis].
AB  - The cellular effects of an extremely-low-frequency (ELF) magnetic field on mouse
      spermatogenesis were assessed by DNA flow cytometry and serum testosterone. Seven
      week old male ICR mice were exposed to a 50 Hz magnetic field the strength of
      which was 1.0 m Tesla. Seven mice per treatment group were exposed for 13, 26, 39
      or 52 days. For each experimental point, an equal number of mice per sham-treated
      group were used as a control and were exposed only to the background field below
      1 mu Tesla in the same room as the treatment group. In the control mice, the
      testis cellular DNA content distribution by flow cytometory was characterized by
      four quantifiable populations; round spermatids (1C), spermatogonia and other
      diploid cells (2C), spermatogonial cells synthesizing DNA (S-phase) and primary
      spermatocytes (4C). In animals exposed for 26 days the number of cells in the 4C
      and the 4C:2C ratio was significantly lower, and the 1C:4C ratio (meiotic
      transformation) was significantly higher than the corresponding control groups.
      In animals exposed for 52 days the cell population in 1C and the 1C:2C ratio
      (total germ-cell transformation) was significantly higher, and the cell
      population in 2C was significantly lower than the corresponding control groups.
      The concentration of serum testosterone in animals exposed for 13 days was
      significantly higher than in the corresponding control group. These changes
      suggest that long-term exposure to an ELF magnetic field had a possible effect on
      the proliferation and differentiation of spermatogonia.

PMID- 9757759
TI  - [The presentation level of interrupted pure tone for inducing the pulse
      phenomenon of continuous white noise].
AB  - When two sounds which have same spectrum but different amplitude are alternated
      without silent gap between the sounds, the lower amplitude sound comes to be
      heard as continuous. This is called "auditory induction" which is one of the most
      interesting auditory phenomena. The fainter sound is called induce and the louder
      sound is called inducer. The authors previously reported that the addition of
      interrupted pure tone to continuous white noise induced the pulsed noise. This
      pulse phenomenon was thought to be a kind of auditory induction; the inducer is
      the noise image of white noise with the silent part of interrupted pure tone and
      the induce is the noise image of white noise with the pure tone part of
      interrupted pure tone. The authors hypothesized that an auditory filter made with
      the pure tone of interrupted pure tone generates the two noise images in the
      continuous white noise. Present experiments were made to investigate the change
      of "the threshold of interrupted pure tone for inducing the pulse phenomenon"
      (TIP) when the presentation level of continuous white noise and the frequency of
      interrupted pure tone are changed. TIP was constant and independent of both the
      amplitude of continuous white noise and the frequency of interrupted pure tone.
      All subjects reported that the higher the frequency of interrupted pure tone is,
      the harder it becomes to hear the pulsed noise image. It is supposed that this
      phenomenon does not contradict the theory of the auditory filter.

PMID- 9757760
TI  - [Effects of acute endurance exercise and 8 week training on the production of
      reactive oxygen species from neutrophils in untrained men].
AB  - We investigated the effects of acute endurance exercise and habitual physical
      activity for health maintenance on human neutrophil function in 12 untrained men.
      The acute exercise condition was a continuous exercise for 90 minutes at the
      intensity of 50% and 55% of maximal oxygen uptake (VO2max) on an ergometer. The
      training program was 3 km jogging three times per week for 8 weeks. The capacity
      of neutrophils to produce reactive oxygen species (ROS) was detected with
      lucigenin-dependent chemiluminescence (LgCL) and luminol-dependent
      chemiluminescence (LmCL) on stimulation with opsonized zymosan (OZ) and phorbol
      myristate acetate (PMA). As for the acute exercise effects, both LgCL and LmCL
      responses of neutrophils, stimulated using PMA consistently increased after
      exercise at 50%VO2max, whereas those stimulated with OZ remained unchanged. At
      55%VO2max, LgCL responses to both stimulants increase maximally 1 h after
      exercise, and then decreased 3 h after exercise, whereas LmCL responses to both
      stimulants increased continuously after exercise at 55%VO2max. These phenomena
      observed at 55%VO2max compared to 50%VO2max suggests the improved capacity of
      producing ROS neutrophils after exercise. The number of neutrophils also
      increased maximally 1 h after exercise, due to the mobilization of band
      neutrophils (shift to the left), suggesting that functional changes was
      associated with cell mobilization. The increase in the capacity of neutrophils to
      produce ROS and marked neutrophilia following the acute endurance exercise
      suggests that a large quantity of ROS may be produced in vivo. As for the
      training effects, the LgCL and LmCL responses were maintained in the exercise
      group as compared to the decreased ones in the control group. The difference
      between the exercise group and the control group was observed only in LgCL
      response to OZ. Humoral immune factors (IgG, IgA, IgM, C3, C4) and serum opsonic
      activity were also unaltered. These phenomena suggest that homeostasis might be
      kept constant in terms of immunity through regular physical activity.

PMID- 9757761
TI  - [The effects of improved diets on the daily intake of environmental contaminants
      as calculated from personal food consumption data, by Monte Carlo simulation].
AB  - In a previous paper, we discussed the Estimated Ecological Daily Intake (EEDI),
      which is a new method for the estimating daily intake of environmental
      contaminants based on individual food consumption data. This method makes it
      possible to identify high-risk cases, using a Monte Carlo simulation for varying
      contamination levels in each food item and permits epidemiological assessment of
      the individual, rather than the population, intake of environmental contaminants.
      We attempted to identify those contaminants whose maximum dietary levels were
      most commonly exceeded. The results obtained were as follows: 1) After a 1,000
      fold extrapolation, performed for each person and contaminant, some cases
      exceeded allowable maximums in dieldrin, lead, cadmium, and total mercury. In
      dieldrin and lead intake, few cases exceeded dieldrin and lead maximums by a
      factor of 2 or 3, but in the cases of cadmium and total mercury, individual
      maximum intake was significantly exceeded. 2) After estimating a high-risk
      individual's times of exceeding the allowance in cadmium intake with dietary
      improvement, we found a 10.5% excess intake after 40% improvement. Clearly, the
      issue of environmental contaminants exposure due to dietary intake is a
      significant one.

PMID- 9757762
TI  - [The development of the Japanese version of the Maslach Burnout Inventory and the
      examination of the factor structure].
AB  - This article presents an evaluation of the factor structures of the Japanese
      version of the Maslach Burnout Inventory (MBI). The MBI is a widely used
      psychometric instrument for measuring 'burnout' developed by Maslach and her co
      workers. The MBI consists of four subscales: Emotional Exhaustion, Personal
      Accomplishment, Depersonalization, and Involvement. The MBI was translated into
      Japanese along with a back-translation and was administered to a sample of 267
      nurses. Various psychometric analyses showed that the Japanese version of the MBI
      has high reliability for the 22 items scored for the frequency dimension. The
      factor analysis using principal factoring with an oblique rotation resulted in
      three factor structures that had different implications from the MBI: Emotional
      Exhaustion/Depersonalization, Personal Accomplishment, and Physical Exhaustion.
      The correlationship between the MBI and the General Health Questionnaire (GHQ),
      measures of depression, showed that burnout was a unique phenomenon.

PMID- 9757764
TI  - [The effects of fluid ingestion and its composition on uric acid metabolism
      during high intensity long term exercise].
AB  - The purpose of this study was to analyze the effects of fluid ingestion and its
      composition on uric acid metabolism after exercise. Six healthy males volunteered
      for the study which was comprised of three different experiments; Exp. 1, Exp. 2,
      and Exp. 3. In all the experiments, subjects performed treadmill exercise
      (70%VO2max) for 70 minutes respectively. For seven hours after exercise, subjects
      ingested mineral water at 10 degrees C ad-lib in Exp. 1, 1.5 times the volume of
      mineral water consumed in the first experiment in Exp. 2, and the same volume of
      sports drink as in the first experiment in Exp. 3. No significant differences
      were observed in oxygen uptake and heart rate during exercise among the three
      experiments, so it was considered that the produced serum uric acid (SUA) levels
      in the three experiments were about the same level. However, the decrease in SUA,
      urinary uric acid excretion (UUA), clearance of uric acid (CUA) and fractional
      excretion of uric acid (FEUA) in Exp. 3, in which the sports drink was consumed
      instead of mineral water were higher than in Exp. 1 and Exp. 2. On the other
      hand, no significant differences were found in Exp. 2 and Exp. 3. A significant
      relationship between UUA and FEUA was found among the three experiments, while
      there was no corrleation between UUA and urine volume. These results show that;
      1) the sports drink ingestion can increase the efficiency of recovery from high
      serum uric acid after exercise, 2) the increase in uric volume due to high
      mineral water intake does not elevate UUA, and 3) the increase in UUA due to
      sports drink ingestion was associated with the increase of FEUA.

PMID- 9757763
TI  - [NK cell activity and subsets of truck drivers along with related factors].
AB  - We investigated the immunity and the main factors that affect the immune system
      of 19 truck drivers as the experimental group and 27 office workers as the
      control group at a transit corporation in Tokyo; all subjects in both groups were
      examined through an assay of NK activity and NK subsets before and after work. At
      the same time, they were asked to complete a questionnaire on their working hours
      per day (WHPD) and driving hours per day (DHPD), in addition to the Health
      Practice Index (HPI), Self-Rating Depression Scale (SDS), Stress Tolerance Check
      List (STCL), and Symptom Checklist (SCL). The results obtained were as follows:
      1. Before work, no difference was seen in NK activity between the experimental
      group and the control group, with both groups showing E:T ratios 5:1 to 20:1.
      After work, the NK activity (E:T = 20:1) of the experimental group was
      significantly lower than that of the control group. 2. In the experimental group,
      the NK activity and NK subsets (CD3-CD16+CD56+, CD3-CD56+, CD3-CD16+) of the
      peripheral blood lymphocytes after work were significantly lower than before work
      (p < 0.05, p < 0.01, p < 0.01). After more than five driving hours, the value of
      the CD3-CD16+CD56+ subset was significantly lower than that after fewer driving
      hours. 3. Correlation coefficients were calculated based on the average value of
      NK activity (E:T = 20:1), CD3-CD16+CD56+ subset, and WHPD, DHPD, and HPI in the
      driving group. NK activity (E:T = 20:1) and DHPD were found to be negatively
      correlated (r = -0.28), as were the CD3-CD16+CD56+ subset and WHPD (r = -0.43)
      and the CD3-CD16+CD56+ subset and DHPD (r = -0.63). On the other hand, NK
      activity (E:T = 20:1), the CD3-CD16+CD56+ subset and HPI were found to be
      positively correlated (r = 0.41 and 0.33).

PMID- 9757765
TI  - [An analysis on a relationship between perinatal mortality and live births of low
      birthweight, in Kumamoto Prefecture, 1968-1994].
AB  - The aims of this investigation were to describe the relationship between
      perinatal mortality rates and the proportions of live births among low birth
      weight (LBW) infants from 1968 to 1994, and to determine risk factors in infants
      of low birth weight. Using vital statistics from 1968 to 1994 of the Japanese
      government and the Kumamoto Prefecture and Maternal and Child Health Statistics
      of Japan from 1968 to 1995, perinatal deaths and live births of infants of low
      birth weight were studied according to national statistics criteria. In Japanese
      and Kumamoto Prefecture, there was an association between perinatal deaths and
      live births of LBW. The significant decline of perinatal mortality rates from
      1968 to 1976, of which the fetal death ratio at 28 weeks and over mostly
      declined, was closely related to the decline of live births of LBW. In this
      period, the improvement of socioeconomic conditions and the comprehensive health
      care provided by the government contributed in improving perinatal mortality
      rates. From 1977 to 1988, the annual variation of Kumamoto was different from
      that of all Japan. Both perinatal mortality rates continued to decline due to a
      general decrease in early neonatal mortality rates. The number of Live births of
      LBW infants in Kumamoto prefecture increased in 1977 and once again started to
      decline in 1982. In 1977, the insufficient maternal-child health care and the
      increase of female workers contributed to increasing rates of live births of LBW.
      Advances in neonatal medicine contributed to the increase in survival rates of
      infants of LBW. Although, after 1982, the improvement of maternal-child health
      care and the perinatal care system contributed to the declining rates of live
      births of LBW. On the other hand, those rates in all Japan continued to gradually
      increase from 1977 to 1988. After 1989, perinatal mortality rates continued to
      decline, and live births of LBW continued to increase in both Kumamoto prefecture
      and all Japan. These results were contrary to the above results from 1968 to
      1976. It was considered that medical advances in the care of pregnant women and
      neonates increased survival rates of the LBW. In future, the perinatal mortality
      rates will appear to approach a minimum constant, that is, a minimum of fetal
      death rates. It is important to reduce the number of LBW infants, particularly
      birthweight of 2000 g-2499 g, with maternal-child health care.

PMID- 9757766
TI  - [Study of skin temperature, microclimate and comfort of clothing of old females
      at rest--ambient temperature x humidity: 30 degrees C. R.H.80%, 30 degrees C.
      R.H.45%, 20 degrees C. R.H.45%].
AB  - Old females are compared to young females for the purpose of studying the
      difference in comfort caused by the environmental variables of temperature and
      humidity as well as the form of clothing. Eight experiments were performed in
      three settings: (a) 30 degrees C R.H.80%; 30 degrees C R.H.45%; and 20 degrees C
      R.H.45%. The ages of the subjects range from 62 to 68 (Mean = 65.17, S.D. = 1.68)
      among old females and from 20 to 23 (Mean = 20.83, S.D. = 0.76) among young
      females. The following results were obtained: (1) The young females were
      sensitive to hot temperatures, while the old females were not. On the other hand,
      the old females were more sensitive to cold temperatures, under 20 degrees C
      R.H.45%, than the young females. In temperatures under 30 degrees C R.H.80%, the
      heat radiation from the young females was higher than that of the old females.
      Under 20 degrees C R.H.45%, the heat radiation from the old females was higher
      than from the young females. The old females are thought to decline in
      physiogenic function due to enduring both hot and cold temperatures. (2) The
      correlation between the temperature in clothes and comfort among the old females
      is not different from the same correlation among the young females. This
      conclusion agrees with previously published studies of the young females. (3)
      Skin temperature and bloodstream are measured, according to clothing form. As a
      result, a long skirt is the highest in thermal insulation, long pants the next
      highest, and a short skirt is the lowest. (4) The effect of thermal insulation
      provided by a lap robe was tested in both groups. The lap robe was found to be
      more effective for the older group than the younger in temperatures under 20
      degrees C R.H.45%. Hence, the role of clothes in offsetting for the decline in
      the thermoregulation function that compensates for environmental change is more
      important for old females than for young.

PMID- 9757767
TI  - [A viewpoint of the revision of the prevention law of infectious diseases].

PMID- 9757768
TI  - [Study of the validity of ADL assessment by Minsei-iin of bed ridden elderly
      cared for at home].
AB  - We studied the validity of assessment of activities of daily living (ADL) by
      minsei-iins of the bed ridden elderly cared for at home. The cases, 66 male and
      128 female elderly in a county of Gunma Prefecture, had been registered by minsei
      iins (non-professional district welfare commissioners) as bed ridden cared for at
      home. Minsei-iins interviewed the case and the caregiver at home, asking them
      about the term of care, the levels of independence in their daily living, and
      seven items of ADL. Out of the 194 cases registered, PTs or OTs interviewed 136
      cases, 42 male and 94 female, and calculated the Barthel index score. The
      Quantification method of the first type was applied to the data to predict the
      Barthel index score. The independent variables were five items of ADL assessed by
      the minsei-iins. The relation was close between the assessment of all items of
      ADL by the minsei-iins and the Barthel index calculated by the PTs or OTs. The
      Quantification method of the first type revealed that bathing, excreting and
      walking contributed most to the measured Barthel index. The multiple correlation
      coefficient was 0.687. There were three cases who scored 100 in the Barthel
      index.

PMID- 9757770
TI  - [A survey of allergic diseases among elementary school children in Saga
      Prefecture. The first report. Prevalence and past history].
AB  - This study was carried out to determine the prevalence of several allergic
      diseases among elementary school children in Saga prefecture. A questionnaire was
      distributed to the parents of 2,795 children in 12 elementary schools located in
      urban, seaside and mountainous areas. The response rate was 92.8%. The prevalence
      rate of allergic diseases among school children was 24.6% (24.5% for boys and
      21.5% for girls). The common types of allergic diseases among boys were allergic
      rhinitis (11.3%), atopic dermatitis (9.7%), and bronchial asthma (5.7%), and
      those among girls were atopic dermatitis (9.7%); allergic rhinitis (6.5%), and
      bronchial asthma (3.7%). Analysis by residential area of the children, showed
      that the prevalence rate of allergic diseases in total was increased in the order
      of mountainous (20.8%), seaside (24.1%) and urban area (28.7%). The most common
      type of allergic diseases was atopic dermatitis in urban and mountainous area,
      while allergic rhinitis was most common in seaside area.

PMID- 9757769
TI  - [Relation between passive smoking at home and dietary intake].
AB  - To investigate confounding factors in the relation of passive smoking to
      diseases, we compared the dietary intake of passive smokers, non-smokers without
      passive smoke exposure, and smokers. The subjects were female respondents to a
      baseline survey, which was conducted as part of a collaborative cohort study in a
      rural area. Of the subjects, 101 females were smokers. A total of 1978 female non
      smokers answered the question about passive smoking exposure at home, including
      1,392 (70.4%) passive smokers and 586 (29.6%) non-passive smokers. Among these
      three groups, the dietary intake of 36 foods (frequency and amount) was compared
      by odds ratios calculated with a logistic regression model. The percentages of
      subjects reporting frequent intake of milk or milk products, carrot or pumpkin,
      tomatoes, oranges, and fruits except oranges, were significantly lower in passive
      smokers than in non-passive smokers (OR = 0.80, 0.74, 0.80, 0.77, 0.79). On the
      other hand, more subjects in passive smokers reported frequent or large intake of
      pork, salt pickled vegetables, soy sauce pickled foods, soft drinks, coffee, and
      moso soup (OR = 1.38, 1.53, 1.32, 1.73, 1.30, 1.33). The dietary pattern of
      passive smokers was similar to that of smokers. In conclusion, in this study,
      passive smokers had different dietary patterns from non-passive smokers'. In
      future research regarding disease with passive smoking exposure, dietary factors
      should be considered as a confounder.

PMID- 9757772
TI  - [Study on blood glucose control of subjects with borderline type abnormality in
      75 G oral glucose tolerance test values. The establishment of a high risk group
      on the basis of yearly observations].
AB  - SUBJECTS AND METHODS: 227 of subjects with a 2-hour plasma glucose concentration
      of 120-199 mg/dl were selected from 413 participants who had two or more 75 g
      OGTT in health examinations from 1987-1995. From these subjects we established 8
      groups according to initial 2-hour plasma glucose concentration 120-199 mg/dl
      stratified by 10 mg/dl, and calculated the total percentages of participants
      whose 2-hour plasma glucose concentration reached 200 mg/dl or greater over a 1-8
      years (2.7 +/- 1.7 years, mean +/- SD) observation period. In 36 subjects who
      were tested annually over a four year period (4 times), the mean values of their
      4 values were analyzed for relationships to coefficients of variation of the 2
      hour plasma glucose. RESULTS: By stratified groups (from lowest to highest) of
      those with an initial plasma glucose concentration of 120-159 mg/dl, 7.4%, 12.1%,
      16.1%, and 15.0% attained values of 200 mg/dl and higher, respectively in 1-8
      years. On the other hand, 29.6%, 29.6%, 39.1%, and 47.4% of those with an initial
      plasma glucose concentration of 160-199 mg/dl moved to a diabetic type after 1-8
      years, respectively. The percentages of those who ended up with levels of 200
      mg/dl and greater at 2-hours tended to increase in subjects whose initial 2-hour
      plasma glucose concentration was over 160 mg/dl in comparison with patients below
      that initial level. CONCLUSIONS: From these results, it appears that subjects
      with 160-199 mg/dl 2-hour glucose concentration, which is considered a borderline
      status, are at high risk for future abnormal levels (> 200 mg/dl at 2-hours) and
      should be managed as a high risk level group for prevention of diabetes.

PMID- 9757771
TI  - [Relationship between dietary fiber intake and food intake patterns of the
      general population, evaluated by a regional nutrition survey].
AB  - This study was performed to estimate the dietary fiber intake calculated using
      individual food intake data and the dietary fiber tables, and to ascertain the
      relationship between food intake patterns and dietary fiber intake of the general
      population. The 805 subjects over 15 years old were obtained from the Tottori
      Prefecture Nutrition Survey. The results are summarized as follows: 1. The
      average dietary fiber intake per capita per day was 18.19 g; 18.67 g in men, and
      17.81 g in women. Dietary fiber intake per energy was different among sexes and
      ages: women had more dietary fiber than men and the aged had more than the young.
      Those who had high fiber intake per energy took green vegetables, fruits, milk,
      soybean products, seaweed and potatoes more frequently, and did not take oil so
      frequently. 2. Total dietary fiber intake from 20 food-group sources was analyzed
      by Multiple Regression Analysis. For both men and women fruits, vegetables and
      soybean products mostly influenced dietary fiber intake. 3. Based on the intake
      of the 20 food-groups obtained from 356 men and 449 women, the correlation matrix
      among these foods was calculated. The correlation matrix was also submitted to a
      Principal Component Analysis. The result of the Principal Component Analysis told
      that food intake patterns were different among the levels of dietary fiber
      intake. Food intake patterns of men and women who had high fiber intake per
      energy had an eating pattern characterized by relatively more non-processed
      vegetable food, bread and milk. 4. The level of blood pressure was significantly
      related to dietary fiber intake per energy in men over 60 years old. In the
      hypertensive men over 60 years old, 23.3% were in the low fiber intake group,
      37.2% in the middle group, and 39.5% in the high group. But in the normal blood
      pressure men over 60 years old, 50.0% were in the low fiber intake group, 8.3% in
      the middle group, and 41.7% in the high group.

PMID- 9757773
TI  - [Characteristics of home care patients with intractable neurological diseases
      (Nanbyo) in Tokyo].
AB  - The purpose of this study was to identify the characteristics of home care of
      patients with intractable neurological diseases. A survey was conducted of
      members of Tokyo Medical Association who were home visit doctors. They responded
      to questions about their patients who have suffered from either Parkinson's
      disease (PD), spinocerebellar degeneration (SCD), or amyotrophic lateral
      sclerosis (ALS), and whose home care have been supported by the care system for
      at least three months. Of 205 survey questionnaires collected, 198 were effective
      to be analyzed. The sample consisted of 105 patients with PD (53.0%), 63 patients
      with SCD (31.8%), and 30 patients with ALS (15.2%). The mean age of the PD was
      75.5 years with a range of 53 to 90, SCD was 66.5 years with a range of 39 to 88,
      and ALS was 58.7 years with a range of 42 to 86. The major findings in this study
      were as follows: 1) The patients who had one or more medical equipment installed
      at the beginning of home care were 30% of ALS, 9% of PD and 18% of SCD. As time
      elapsed, patients who needed to have some medical equipment installed increased
      in ALS greater than in PD and SCD. 2) The home doctors predicted that the
      condition of 37% of ALS patients, 9% of PD, and 8% of SCD would probably be
      deteriorating within one month. 3) Of the 30 patients with ALS, 47% experienced
      hospitalization three times or more compared to 27% of PD and 21% of SCD. The
      most prevalent reason for hospitalization for ALS was respite of caregivers, PD
      and SCD, however, were hospitalized for control of prescription, a change for the
      worse, or treatment of other diseases. 4) Ninety percent of ALS caregivers felt
      extremely tired or slightly tired. Their home doctors responded that 83% of ALS
      caregivers did their best in caregiving. 5) ALS patients utilized social
      resources such as volunteers, care workers, services of supply and maintenance of
      medical equipment, and emergency care for 24 hours more than SCD and PD. In the
      conclusion, ALS patients experienced the highest hospitalization of the three
      diseases and respite of family caregivers was necessary. They showed a higher
      utilization of various social resources than other diseases. It is important to
      consider these characteristics of home care patients by diseases in order to
      prepare and develop the necessary support system of home care for the intractable
      neurological patients.

PMID- 9757774
TI  - [The health and welfare system for elderly in France].
AB  - Dichotomy is the main characteristic of the Health and Welfare system in France.
      This system lies on two distinct fields, the medical field which is managed by
      the National Government, and the social field managed by the Local Government.
      The French home care policy for the elderly has developed a large number of
      services to assist in activities of daily living, to provide nursing and medical
      care at home, to improve living conditions, to maintain social relationships, and
      to postpone institutionalization and hospitalization, respectively. The main home
      care service is represented by "home helpers" who provide maid Notiniralics
      services. The second widely used service is the "home care service" performed by
      a team of nurses, assistant-nurses, psychologists, physiotherapists. This team
      provides nursing care and assistance in activities of daily living. As for
      institutions for the elderly, they are divided into welfare and medical
      institutions. The welfare institutions include social establishments like shelter
      homes and nursing homes. The medical institutions are mostly represented by long
      term care hospitals. One of the main goals of the aging policy is to create
      medical wards in welfare institutions in response to the increased dependency of
      the institutionalized elderly. Recent experimental and innovative concepts have
      been established, such as "shelter homes for dependent elderly" for physically or
      cognitively impaired elderly.

PMID- 9757775
TI  - [Inflammation of the pelvis minor].
AB  - Pelvic inflammatory disease (PID) is the must important gynecologic infectious
      disease. It causes not only serious clinical symptoms, life threatening
      complications, but also severe damage to the female upper reproductive tract.
      Among its important sequale are infertility due to tubal occlusion, ectopic
      pregnancy, dyspareunia, and chronic pelvic pain. The must important causative
      organisms are Neisseria gonorrhoeae, Chlamydia trachomatis, as well as anaerobic
      and facultative bacteria found in the vaginal flora of women with bacterial
      vaginosis. The author reviews the latest developments regarding the epidemiology,
      etiology diagnostics, medical and surgical therapy of the disease. The importance
      and possibilities of prevention are discussed.

PMID- 9757777
TI  - [A new technic in the management of hydrocephalus: neuro-endoscopy].
AB  - Conventional valve shunting for treatment of hydrocephalus has a high rate of
      long-term complication. After a brief historical review of neurosurgical
      endoscopy the authors present the different indications and methods of
      neuroendoscopy. Between 1995 and 1997 twenty-two pediatric patients underwent
      endoscopic surgery at National Institute of Neurosurgery. Twelve of them had
      third ventriculo-cistemostomy, and cystic wall fenestration was performed in ten
      children. All but one patient benefited from this minimally invasive endoscopic
      technic. Minor transient complications were seen in three cases, and only one
      patient had long-term pupillary dilatation due to the surgical procedure.

PMID- 9757776
TI  - [Current status of the management of upper gastrointestinal hemorrhage at a
      specialized hospital unit].
AB  - The prevalence of bleeding of the gastrointestinal tract is around 100/100,000
      adults/year. These events need special diagnostic and therapeutic approach, which
      previously was located mostly to surgical departments. At the beginning of 1996 a
      specialized ward ("gastrointestinal bleeding unit, GBU") was created at the 2nd
      Dept. Medicine of the University Medical School of Debrecen. The authors give an
      account about their experiences with the first 250 cases, try to establish the
      optimal and necessary conditions and analyse the consequences of their newly
      developed "risk-score" system. The overall mortality was 9% during this period
      and surgical intervention proved to be necessary in only 10 cases. On the basis
      of the collected experiences, they are convinced that the described and
      elaborated model can well be used for the proper, up-to-date management of
      gasrointestinal bleeding disorders. As next they suggest an overall, regional
      organisation of such units, together with the correct determination and provision
      of the financial background.

PMID- 9757778
TI  - [Bcl-2 expression in testicular cancer in relation to tumor progression].
AB  - Bcl-2 expression has been studied extensively in a variety of human tumors.
      However, there are lack of clinical data in regard to its expression in germ cell
      testicular tumors (GCTTs). In this study we screened bcl-2 expression in 70
      patient with GCTTs using the immunohistochemistry (IHC) and streptavidin biotin
      alkaline phosphatase method. Furthermore, we correlated this expression with
      metastatic behaviour and clinical stage. Overall, 41 (58%) carcinomas stained
      with anti-bcl-2 (DAKO-124) monoclonal antibody, By histologic type, these lesions
      included 11 (42.3%) of 26 seminomas (S) and 30 (68.18%) of 44 non seminomatous
      germ cell testicular tumors (NSGCT). The incidence of bcl-2 immunostaining was
      higher (P = 0.05, two-tailed, Fisher's test) in NSGCT than in seminomas. Bcl-2
      expression was higher in tumors from metastatic patients than in tumors from
      metastatic-free patient (p = 0). There was a significant difference between the
      three stages of disease as to the expression of bcl-2 (chi 2 = 0). High level of
      bcl-2 was clearly dominant in tumors of advanced stages. The present finding
      revealed that bcl-2 expression occurs in GCTTs. Further, they suggested that bcl
      2 is associated with a more progressed malignant phenotype in these tumors.

PMID- 9757779
TI  - [Renal candidiasis following treatment of infantile osteomyelitis].
AB  - Systemic candidiasis with renal complications is a rather rare phenomenon in
      young infants. Authors report on a 4.5 month-old baby (preterm) who, during an
      antibiotic therapy of wide spectrum--because of osteomyelitis--acquired a mycotic
      infection causing bilateral pyelon and pyeloureteral obstruction. In addition to
      systemic antimycotic therapy surgical intervention was needed to eliminate the
      mycotic bezoar.

PMID- 9757780
TI  - [300th anniversary of the birth of Bernhard Siegfried Albinus, reformer of
      anatomy].

PMID- 9757781
TI  - [Diagnostic value of cutaneous manifestation].

PMID- 9757782
TI  - [Newest contraceptive agents].

PMID- 9757783
TI  - [The evaluation of breed-specific defects in dog breeds from an animal welfare
      viewpoint].
AB  - Issues of breed defects such as morphology, physiology or behaviour in pure-breed
      dogs, are briefly discussed. Suggestions for various kinds of improvements are
      made, particularly concerning legislation, analysis of pedigree to avoid
      undesirable breed characteristics and what breeding clubs, individual breeders,
      judges, future dog owners and veterinarians could and should do about these
      problems; these are followed by summary conclusions.

PMID- 9757784
TI  - [Classical swine fever in 1993 in Switzerland: molecular-epidemiologic
      characterization of the virus isolate].
AB  - RT-PCR followed by direct nucleotide sequencing of the amplified cDNA was carried
      out to analyse most of the 5' nontranslated region (5'NTR) of classical swine
      fever virus (CSFV) isolates from the five 1993 disease outbreaks in Switzerland.
      Sequence data were compared to other CSFV strains, and dendrograms were
      constructed in order to determine the phylogenetic relationship of the Swiss
      virus strains. Dendrograms formed by the analysis of different parts of the 5'NTR
      were compared. It was shown that all Swiss isolates were related to other CSFV
      strains involved in disease outbreaks in Europe in the 1990s. Two of the isolates
      were indistinguishable from a CSFV strain isolated from wild boar meat imported
      from China into Austria in 1993. The risk of introducing classical swine fever by
      improperly treated swill and, in particular by importing wild boar meat is
      discussed.

PMID- 9757785
TI  - [The diagnosis of patellar luxation in small animals].
AB  - A standard diagnostic procedure for patellar luxation is described. It is based
      upon the patellar luxations grade 1 to 4, which have been published before, and
      contains additional definitions in terms of the animals positioning toward the
      examiner.

PMID- 9757786
TI  - [Case presentation in small animal medicine].
AB  - A 11 year old female spayed Jack Russel Terrier was diagnosed with diabetes
      mellitus and ketoacidosis. After successful initial treatment metabolic control
      deteriorated although insulin dosage was increased. Cushing's syndrome was
      diagnosed and treatment with Lysodren was started. As a result blood glucose
      concentrations decreased. The difficulty to diagnose Cushing's syndrome in some
      diabetic dogs is discussed.

PMID- 9757787
TI  - [Morphology and molecular biology of malignant soft tissue sarcomas].
AB  - Malignant soft tissue tumors are classified and named according to cellular
      differentiation and thus the non-neoplastic soft tissue they imitate. The topical
      WHO classification already comprises more than 140 entities and tumor subtypes,
      but the process of defining new tumor variants will go on. Questions of
      nomenclature are discussed briefly with laying special emphasis on the non
      undisputed concept of malignant fibrous histiocytomas. Without doubt, this
      diagnosis is made too frequently by which it has become to a collective name for
      unclassifiable pleomorphic sarcomas. For the time being nobody is able to say
      whether or not the malignant fibrous histiocytoma will remain an entity. Likely,
      fibrosarcomas and hemangiopericytomas are defined as exclusion diagnosis, as
      well. The diagnosis of malignant soft tissue tumors is based on recognizing the
      cellular line of differentiation. This is frequently possible at light
      microscopic level, sometimes additional diagnostic methods are required. The most
      important adjunct method is immunohistochemistry. Because aberrant
      differentiations and unexpected immunohistochemical reactions are known the use
      of a panel of antibodies is necessary. In the last years soft tissue tumors has
      increasingly been characterized by molecular biological methods. The results are
      of significance for understanding sarcoma pathogenesis and may be used for
      diagnosis, as well. Chromosome translocations are explained and rhabdomyosarcomas
      are taken as example for demonstrating the diagnostic significance of molecular
      biological/cytogenetic findings. Molecular biology may also aid in defining the
      histopathologic features of an entity as shown for intraabdominal desmoplastic
      small cell tumors. Eventually, heterogeneity in soft tissue sarcomas is addressed
      and discussed in view of its importance for diagnosis, classification and therapy
      as well as for development of sarcoma progression.

PMID- 9757788
TI  - [Surgical aspects in the multidisciplinary treatment of soft tissue sarcomas].
AB  - Sarcomas are rare malignant tumors with a large variety of histologic subtypes.
      The surgical approach depends more on the histologic grade, the size and the site
      of the tumor. Radiologic diagnosis relies predominantly on MR-imaging.
      Discernible improvements have taken place in soft tissue sarcoma patient
      survivorship and quality of life over the past 20 years, with overall 5-year
      survival currently at approximately 50-80%. The place of surgery in the treatment
      of soft-tissue sarcoma is defined in the light of a review of the recent
      literature. Radical surgical resection is the mainstay of therapy. Local
      recurrence is the most common type of failure. Local recurrence is resectable and
      limb preservations possible in the majority of patients. Survival after treatment
      of local recurrence is determined mainly by the grade and secondarily by the size
      of the tumor. The essential risk factor for local recurrence is the quality of
      surgical resection, defined by the definitive resection margins. A lateral safety
      margin of 5 cm and of 2 cm to the depth should be respected. In sarcoma of the
      extremity the compartment is defined based on clinical, radiographic,
      histopathologic and operative findings. The use of muscle flaps to fill the
      surgical defects can improve the functional result and reduce the complication
      rate. Only about 5% of the patients need amputation. Evaluation of functional
      results must be based on objective criteria. In retroperitoneal sarcoma the
      significant factors for determining prognosis are grade and completeness of
      exzision. Multidisciplinary treatment according to common protocols is essential.
      Shifts in treatment have taken place over the past decade, from single-modality
      treatment involving radical surgery with compartment resection to sophisticated
      limb-salvage strategies combined with radiation therapy. In case of inadequate
      surgery e.g. in a large tumor with positive margins in high-grade soft tissue
      sarcomas the addition of radiotherapy can improve local control, but cannot
      ensure that obtained by adequate surgery. Patients with large (greater than 5
      cm), high grade soft tissue sarcoma are at high risk for distant recurrence and
      disease-related mortality. Investigations of combined modality therapy with newer
      chemotherapy agents and dose intensification treatment strategies are warranted.

PMID- 9757789
TI  - [Surgical management of soft tissue sarcomas: principles of resection and
      reconstructive plastic procedures].
AB  - 1. Adequate complete surgical resection with a oncologic radical or wide margin
      of normal tissue represents the most important measure to prevent a local
      recurrence. Limited excision with "shelling-out" of the tumor, through its
      "pseudocapsule" almost invariably means positive microscopic margins. The
      pathohistologically or macroscopically marginal or intralesional positive
      resection margins make a salvage surgery necessary. 2. A close safety margin of <
      1 cm due to neighboured anatomic structures indicates a high risk of local
      recurrence and makes an adjuvant radiotherapy mandatory. Plastic-reconstructive
      surgery should prepare the radiotherapy fields, to avoid cavities or ulcerations.
      3. Facts should be stated in the clinical record and the operation report, e.g.
      the safety margin should be defined by the surgeon and the pathologist; the
      histopathologic stage and grade are absolutely basic requirements. If necessary,
      a second histopathologic review should be asked for. 4. Tumor resection and
      reconstructive oncoplastic measures should correspond individually to the
      oncologic parameters, to the functional demands and to the age of the patient. 5.
      Multidisciplinary cooperation in a tumorboard is a precondition for an adequate
      treatment.

PMID- 9757790
TI  - [Adjuvant chemotherapy in early soft tissue sarcoma and palliative chemotherapy
      in advanced soft tissue sarcoma in adults].
AB  - Adjuvant chemotherapy (chth): The place of postoperative adjuvant chth after
      complete resection of a primary tumor (R0) is not well established. 13 adjuvant
      chemotherapy trials with a variety of combinations and most often doxorubicin
      alone in different regimens were compared to a control group without
      chemotherapy. Only 2 reports showed a difference in overall survival and 4 some
      gain in disease-free survival. New studies began with defined inclusion criteria
      and a control arm without chemotherapy. There are only some risk factors coming
      into consideration: deep seated tumors with histologic grade 2 and all grade 3
      cases. Adjuvant chemotherapy appears justified only within these studies. The
      potential side effects of adjuvant chemotherapy outside of these trials are
      detrimental (e.g. 10% cumulative risk of cardiomyopathy after ADM; risk of
      secondary leukemias) and a benefit is not known. Primary induction chth:
      Preoperative neoadjuvant chth has to be reserved for studies. They are performed
      in case of deep seated large primary tumors, not suitable for R0-resection
      without mutilation. Palliative Chth: In metastatic or locally not curative
      resectable disease treatment is palliative. The aim of treatment is the relief of
      existing symptoms or the avoidance of threatening complaints and possibly
      prolongation of life. The combination of ADM and Ifosfamide (IFO) is commonly
      used although its superiority to ADM monotherapy is not proven. As second line
      chemotherapy in case of tumor resistance high dose IFO-monotherapy can be put up
      for discussion. Myeloablative high-dose-poly-chth with stem cell transplantation
      remains an experimental approach.

PMID- 9757791
TI  - [Radiotherapy of soft tissue sarcomas].
AB  - Soft tissue sarcomas are uncommon neoplasms that represent approximately 1% of
      all malignancies. It is clear that sarcomas require a therapeutic approach that
      establishes local control and thereby eliminates the potential of metastasis for
      patients with truly limited disease. Localized sarcomas are generally treated by
      surgery. Excision must be complete, with a wide margin of normal tissue, and
      along anatomic planes, or recurrence will almost certainly follow. Amputations
      are still occasionally required, although limb salvage procedures are being used
      increasingly, particularly in the context of multimodality therapy with
      irradiation or chemotherapy. Radiotherapy can be highly effective for improving
      local control and is used as adjuvant therapy, either preoperatively or
      postoperatively. In case of non-in-sano-resection a salvage surgery is indicated.
      Use of adjuvant postoperative radiotherapy allows for more conservative surgery
      without compromising local control, and therefore often may allow limb salvage
      where amputation might otherwise be necessary, e.g. in case of R1- or R2
      resection without a new resection, a close margin or large tumors with histologic
      G2 or G3 grading and in case of local relapses. Local control rate of 90% are
      reported for the combination of pre- and postoperative radiotherapy. Prognosis is
      still limited by distant metastases. In case of unresectable tumors neutron
      radiotherapy results in 50% local control. New approaches e.g. hyperfractionated
      accelerated radiotherapy, interoperative radiotherapy and chemoradiotherapy are
      promising perspectives, which are being evaluated in clinical studies. Desmoid
      tumors benefit of postoperative radiotherapy in case of R1-resection or relapse.

PMID- 9757792
TI  - A community medicine project involving an educational session in sexually
      transmitted diseases for high school students.
AB  - The University of South Dakota School of Medicine requires that students
      undertake a Community Medicine project of their choice as part of the Family
      Medicine course in the third year of medical school. One of these projects
      consisted of a presentation given to a high school class in Sioux Falls, South
      Dakota, on sexually transmitted diseases. The effectiveness of the presentation
      in increasing the students' knowledge on this subject was measured by a pretest
      and posttest multiple choice examination. The students' knowledge was clearly
      increased by the presentation.

PMID- 9757793
TI  - Newer-generation fluoroquinolone antibiotics.

PMID- 9757794
TI  - A medical student's experience in Venezuela.

PMID- 9757795
TI  - [The ever-present future].

PMID- 9757796
TI  - [Endovascular treatment of abdominal aortic aneurysm. Preliminary experiences
      with the Talent endoprosthesis].
AB  - BACKGROUND: The treatment of infra-renal abdominal aortic aneurysms (AAA) with
      endovascular stent-graft prostheses is receiving increasing attention as an
      alternative to major abdominal surgery. Numerous systems are under clinical
      investigations. We report our preliminary clinical results with the new Talent
      straight and bifurcated endografts. METHOD: We treated 5 patients with 3 straight
      and 2 bifurcated stent-grafts implanted by surgical femoral arteriotomies and
      placed under fluoroscopic guidance. Control CT and angiographic examinations were
      performed during an average follow-up of 5.3 months. RESULTS: In the first
      patient the procedure had to be converted to an open surgical operation to repo
      sition the distal end of the prosthesis. We had no mortality, or major systemic
      complication. Three patients had a postimplantation syndrome. All aneurysms
      showed a decreased size at 3 months, in spite of 3 small persisting leaks.
      CONCLUSION: The Talent endograft is safe, and efficacious in the endovascular
      treatment of AAA. This method requires a good cooperation between the vascular
      surgeon and the interventional radiologist. Learning curves influence preliminary
      results.

PMID- 9757797
TI  - [Minimally invasive internal saphenous vein harvesting for coronary artery
      bypass].
AB  - Harvesting of the great saphenous vein for coronary artery bypass grafting is
      usually performed through long cutaneous incisions. We report our experience of
      minimally invasive harvest of the saphenous vein using the "Mini Harvest System".
      This device is composed of a blade coupled to a light source. Through a small
      cutaneous incision, the blade is placed under the skin and allows progressive
      dissection of the vein under direct vision. We compare this technique ("minimal
      invasive" group, n = 48) to the conventional method in which extensive incisions
      are performed along the saphenous vein course ("standard", n = 54). Both groups
      are comparable in term of age, sex, diabetes, peripheral arterial disease or
      obesity. The number of bypass performed is also comparable in the two groups. The
      ratio of the mean length of the cutaneous incision and the mean length of the
      vein was 35.4 +/- 5.9% for the "minimal invasive" group and 104.5 +/- 23.3% for
      the "standard" group (p < 0.001). The local complication rate is significantly
      reduced with a reduction in local post-operative pain (2% vs. 17%, p = 0.01), a
      better healing (100% vs. 79%, p = 0.01), a reduction in hematoma (31% vs. 52%, p
      = 0.03) and in oedema (37% vs. 59%, p = 0.03). We conclude that besides the
      evident aesthetic benefit, minimally invasive harvest of the saphenous vein
      allows for a better cicatrization and reduces the post-operative discomfort
      without compromising the aorto-coronary bypass procedure.

PMID- 9757798
TI  - [How to do: initial experiences with a new device in minimally invasive heart
      surgery].
AB  - A special surgical technique is required for minimal-invasive cardiac surgery.
      The view for the coronary artery anastomosis under beating heart conditions is
      important and coronary artery blood might prevent a clear view of the opened
      coronary artery vessel. A new system called VisoFlo promises to improve
      visualisation at the surgical site. VisoFlo delivers a column of air to help
      provide a clear view of anastomosis site and in addition has a controllable mist
      to help prevent desiccation of the graft and surrounding tissue. This system was
      tested on 45 patients with coronary-artery-bypass graft surgery under beating
      heart conditions and at 65 patients with standard coronary-artery-bypass graft
      surgery. Our conclusions are, that the VisoFlo system is easy to use, guarantees
      a clear view of the anastomosis site and the surgical work will not be impaired.

PMID- 9757799
TI  - ["Minimally invasive" surgical closure of the patent foramen ovale].
AB  - AIM OF THE STUDY: After the abdomen and the thorax, the cardiac approach seems to
      be the logical next step in development of minimally invasive surgery. We report
      our initial experience in closure of patient foramen ovale (PFO) through a mini
      thoracotomy. METHOD: A cardio-pulmonary bypass is initiated through canulaes
      introduced into the external iliac artery and vein. A right anterior mini
      thoractomy is performed in the fourth intercostal space and a video-endoscopic
      camera is introduced through a trocar placed more laterally. The pericardium is
      opened anteriorly to the phrenic nerve. A venous canula is introduced into the
      superior vena cava and connected to the extracorporeal circuit. A ventricular
      fibrillation is provoked and both vena cavaes are clamped before the right atrium
      is opened. The PFO is closed with a double running suture. DISCUSSION: From
      November 1996 to march 1997, 4 patients were operated that way. The mean
      operation time was 212 +/- 17 minutes, the mean CPB time was 73 +/- 32 minutes,
      and the mean fibrillation time was 32 +/- 15 minutes. Echocardiography was
      performed at the end of the operations and at day 7. No residual shunt was
      detected and the cardiac function was not changed compared to the preoperative
      examination. CONCLUSION: Closure of a PFO can be performed through a mini
      thoracotomy, with good results. With growing experience, the "minimally invasive"
      approach shall rapidly become a standard technique for this indication.

PMID- 9757800
TI  - [Hemodynamic effects of maximum laser transmyocardial revascularization].
AB  - The aim of this study was to determine the haemodynamic reaction of a heart in
      which the left lateral wall was bored with laser channels until cardio-vascular
      collapse. Four calves were selected for the study. Series of five channels were
      bored with a 1.75 mm diameter laser probe. Each series was followed by a break of
      three minutes at the end of which haemodynamic parameters were recorded. The
      evolution of these parameters then underwent linear regression analysis.
      Calculations were made according to the percentage of the total number of
      channels, in order to standardize the results between the animals. Respectively
      150, 155, 270 and 285 channels were bored. In each case, all haemodynamic
      parameters dropped abruptly during the last series of channels. Central venous
      pressure, mean pulmonary artery pressure, wedge pressure, mean arterial pressure
      and cardiac output followed a linear regression slope which did not significantly
      differ from zero. Heart rate only increased progressively with a liner regression
      slope significantly different from zero. In this acute model, haemodynamic
      parameters, except heart rate, did not correlate to the extent of damage imposed
      on the left ventricle. Thus, the presence of haemodynamic stability does not
      exclude important myocardial damage in an acute situation. This can be found in a
      clinical setting.

PMID- 9757801
TI  - Tissue engineering: a new approach in cardiovascular surgery--seeding of human
      fibroblasts on resorbable mesh.
AB  - INTRODUCTION: In tissue engineering the material properties of synthetic
      compounds are manipulated to enable delivery of dissociated cells onto a scaffold
      in a manner that will result in in vitro formation of new functional tissue. The
      seeding of human fibroblasts on resorbable mesh is a precondition of a successful
      creation of human tissue such as autologous cardiac valves. MATERIAL AND METHODS:
      Polymeric scaffolds (n = 12) composed of polyglycolic acid (PGA) with a fiber
      diameter of 12-15 mm and a polymer density of 70 mg/ml were used as square sheets
      of 0.3 x 1 x 1 cm. Fibroblasts (passage 5), harvested from human foreskin, were
      seeded (3.4 x 10(6)) and cultured over a 3 week period on a PGA mesh. RESULTS:
      Microscopic examination of the seeded mesh demonstrated that the human
      fibroblasts were attached to the polymeric fibers and had begun to spread out and
      to divide. Electron microscopy showed a continuous distribution and formation of
      the cells throughout the "polymeric architecture". Spotlike hydrolysis of PGA
      fibers was observed. After 3 weeks the seeded scaffolds resembled a solid sheet
      of tissue. CONCLUSION: These preliminary results, successful seeding of human
      fibroblasts on a PGA mesh, represent a first basic step on the way to construct
      human tissue such as autologous cardiac valves and demonstrate that tissue
      engineering might be a promising new device in therapy of cardiovascular disease.

PMID- 9757802
TI  - [Intraoperative and postoperative microdialysis measurement of the human heart-
      feasibility and initial results].
AB  - STUDY OBJECTIVE: Microdialysis measurements of human cardiac metabolism during
      and after cardiac operations have not been published up to now. The goal of this
      study was to evaluate feasibility of the method in a clinical setting and to
      interpret first results. PATIENTS AND METHODS: In 5 patients microdialysis
      measurements were made in regular intervals during aortocoronary bypass surgery.
      Analysis of dialysate was done by high performance liquid chromatography or
      enzymatic fluorometry. In the last 2 patients measurements were also taken during
      the postoperative course up to the time of extubation. RESULTS: During aortic
      cross clamping a mean 7-fold rise of the radical scavenger glutathione was
      observed (range 0.9-15.4; p = 0.06). During reperfusion the
      glucose/lactate(Glc/Lac)-rate rose from 0.4 to 3.1 (p = 0.02). Concentrations of
      ascorbic acid, cysteine and uric acid remained neutral or showed no regular
      changes. In the 2 patients who were also observed postoperatively, lactate rose
      significantly at 190 min and 340 min postoperatively (decrease in Glc/Lac-ratio
      from 2.5 to 0.4 and 2.0 to 0.4 respectively). CONCLUSIONS: Microdialytic
      measurements of metabolic parameters can be performed on the human heart in a
      clinical setting. So far no complications have been observed and the
      microdialysis probe can be installed in such a fashion, that it can be easily
      removed transcutaneously during the postoperative course. Substances that are
      important in ischemia and reperfusion can be measured and their concentrations
      show changes that are not just artefacts. Postoperatively, metabolic alterations
      may be observed in the myocardial septum that are not recordable with
      conventional techniques (i.e., pressure measurements, cardiac output, ECG).

PMID- 9757803
TI  - [The significance of endothelial adhesion molecules in heart surgery].
AB  - Myocardial ischemia and reperfusion is a common event in cardiovascular surgery
      patients. The endothelium has been shown to play a key role in the injury
      suffered after ischemia and reperfusion. When endothelial cells became hypoxic
      followed by reoxygenation they become activated to express endothelial adhesion
      molecules followed by the migration of neutrophils into the tissue. These changes
      may contribute to the early postoperatively myocardial dysfunction. An increased
      understanding of the interaction between leukocytes and endothelium may allow to
      develop new therapies in future.

PMID- 9757804
TI  - [The floating joint injury of the lower and upper extremity--epidemiology,
      therapy and results in 40 extremities].
AB  - GOAL: Floating Joint Injuries (FJI) are resulting from high energy traumas and
      are often combined with additional neuro/vascular damage. The high incidence of
      severe open or closed soft tissue injuries is complicating the initial management
      and requires a broad surgical know-how also in minimal-invasive fixation
      techniques. In a retrospective analysis of our cases treated between 1980 and
      1995, we try to find out some important therapeutical feedback for the future.
      MATERIAL AND METHODS: Of the 37 patients, 33 had a FJI of the lower (2 bilateral)
      and 7 patients of the upper extremity. 90% were road traffic injuries, 75% showed
      an open fracture situation and 25% an associated neuro-vascular injury. All
      fractures were stabilised within the first hours, femur, humerus and forearm in
      one step, the tibia in 33% in two steps (initial external fixator ...). 80% of
      the FJI have been reexamined after 1-2 y. RESULTS: Local complication: Femur:
      4/33 (1 infection, 2 refractures, 1 non-union). Tibia: 11/33 (5 infections, 4
      delayed/non-unions, 2 malalignements). Humerus: 0/7. Forearm: 1/7 (1
      malalignement). 1-2 y-results: Very good-good: Femur: 26/27 (96%). Tibia: 23/27
      (85%). Humerus: 4/5. Forearm: 3/5. DISCUSSION: FJI should be stabilised as soon
      as possible in a way allowing for early functional aftercare of the affected
      joint. Most complications are observed in the proximal tibia fracture because of
      the thin and therefore often severely (open or closed) injured soft tissue cover.
      Despite a staged procedure, there exists a high complication rate, which probably
      can be reduced in the future by the single-step use of the hybrid external
      fixateur.

PMID- 9757805
TI  - [Diagnosis and therapy of vascular injuries in posterior knee dislocation].
AB  - AIM: We demonstrate the management and treatment of dislocation of the knee
      associated with vascular injury. The goal of the treatment is to avoid
      complications due to ischemia. The injured vessel can be repaired either by
      direct suture or by interposition of a saphenous vein graft. Capsule and
      ligaments should be reconstructed secondarily. PATIENTS AND METHODS: The charts
      of ten patients treated in the Division of Traumatology of the University of
      Zurich between 1979 and 1996 have been retrospectively checked. RESULTS: In eight
      of ten patients the injured vessel has been reconstructed with a saphenous vein
      graft, in one patient the artery has been repaired by direct suture. In one
      patient a flap of the intima has been refixed by endarterectomy. In five patients
      the knee has been stabilised with a transfixation (external fixation). In two
      patients the ligaments and the capsule were reconstructed at the time of vascular
      repair, in seven patients the reconstruction has been performed secondary.
      CONCLUSIONS: In case of a dislocation of the knee the examination of the vessels
      is mandatory. In case of a critical perfusion the "on table"--angiography is the
      procedure of choice. As an alternative method duplex sonography has been
      established. The vascular reconstruction is performed by saphenous vein graft
      interposition. We recommend to reconstruct ligamentous and capsular structures
      secondary.

PMID- 9757806
TI  - [Diagnostic reliability of 0.2 Tesla dedicated MRI low-field strength equipment
      in traumatology].
AB  - Anatomical dedicated low-field-strength MR imaging (non-whole-body-systems) has
      been developed for examinations of the peripheral joints. It has several
      advantages compared to high-field-strength MR imaging (whole-body-systems). The
      dimensions are small, the noise is not as bad as in whole body systems and people
      do not suffer of claustrophobic attacks. However, our results of a prospective
      blinded study in 56 patients with three different kinds of peripheral joint
      injuries demonstrated that the 0.2 T dedicated system showed a significant lower
      rate of diagnostic accuracy compared to middle and high-field-strength MR imaging
      and scored with obvious lower image quality ratings.

PMID- 9757807
TI  - [Value of 3D CT in diagnosis and treatment of fractures of the tibial plateau].
AB  - A precise classification and an optimal understanding of tibial plateau fractures
      are the basis of a conservative treatment or adequate surgery. The aim of this
      prospective study is to determine the contribution of 3D CT to the classification
      of fractures (comparison with standard X-rays) and as an aid to the surgeon in
      preoperative planning and surgical reconstruction. Between November 1994 and July
      1996, 20 patients presenting 22 tibial plateau fractures were considered in this
      study. They all underwent surgical treatment. The fractures were classified
      according to the Muller AO classification. They were all investigated by means of
      standard X-rays (AP, profile, oblique) and the 3D CT. Analysis of the results has
      shown the superiority of 3D CT in the planning (easier and more acute), in the
      classification (more precise), and in the exact assessment of the lesions
      (quantity of fragments); thereby proving to be of undeniable value of the
      surgeon.

PMID- 9757808
TI  - [Long-term peridural anesthesia and minimally invasive therapy of arthrofibrosis
      of the knee joint].
AB  - We report on our experiences with continuous epidural anesthesia after
      arthrolysis of the knee joint. The restoration of knee motion is the main goal of
      our treatment regimen which includes daily passive full mobilisation of the knee
      joint with a continuous epidural catheter after arthroscopic lysis and a
      functional after treatment with full weight bearing. From December 1992 to
      November 1996 32 arthroscopic lysis have been performed at the Surgical
      Department of Triemli Hospital in Zurich, Switzerland. The indications for prior
      knee surgery included 22 ACL reconstructions, 4 sustained fractures about the
      knee and 6 miscellaneous etiologies. Arthroscopic lysis was performed for any
      failure in improving knee motion despite intensive physical therapy. According to
      Gassen et al. [4] we found one (3.1%) very severe, 5 (15.6%) severe, 12 (37.5%)
      moderate and 14 (43.8%) minor cases of arthrofibrosis. After 8 months on average,
      a second lysis had to be performed in six cases. All had an ACL reconstruction as
      prior surgery, in four out of these six patients only physiotherapeutic after
      treatment was performed after the first lysis, 2 patients developed a symptomatic
      patella baja. At the end of the treatment after 10 months on average, 16 (50%)
      cases showed a very good, 7 (22%) a good, 5 (16%) a satisfactory and 4 (12%) a
      poor result concerning range of motion. We think that a daily passive full
      mobilisation under regional anesthesia with a continuous epidural catheter is the
      key to hold the intraoperatively reached range of motion especially for moderate
      to very severe cases of arthrofibrosis.

PMID- 9757809
TI  - [Antegrade or retrograde intramedullary nailing in diaphyseal or sub-capital
      humeral fractures in the adult].
AB  - The aim of this retrospective study was the evaluation of three current medullary
      nailing techniques and their approach related problems in diaphyseal and proximal
      humeral fractures. 28 patients (15 female, mean age 65 y; 13 male, mean age 53 y)
      with either diaphyseal (n = 22) or proximal humeral (n = 6) fractures treated
      with different nailing systems were reviewed (mean follow up 18.3 months). Two
      main groups were formed according to the surgical approach: an anterograde
      nailing group (AN), stabilized with Seidel (Howmedica) nails (n = 12) versus a
      retrograde nailing group (RN) with either Prevot (Landos) nails (n = 7) or
      Hackethal (Ulrich) nails (n = 9). The two groups were comparable regarding to
      age, follow up and fracture type. The subjective scores (global function, all day
      activity, pain, ROM) of the two groups (AN and RN) showed no statistically
      significant differences. Subacromial impingement led to reoperation in 50% (6/12)
      of the AN patients (Seidel nail). In 3/16 patients a reoperation was necessary
      due to secondary proximal or distal nail migration (Hackethal or Prevot nails).
      Delayed union was found either in one. Seidel or one Prevot nailed humerus. No
      postoperative infections or neurological problems (3 preoperative radial palsies
      recovered) due to the operative pro cedure were seen. The AN related subacromial
      impingement seems to be more disabling than RN related reduction of elbow
      function (extension deficit).

PMID- 9757810
TI  - [Isolated coracoid fracture--open reposition and osteosynthesis--report of 3
      cases].
AB  - Usually coracoid-fractures are "chain-injuries" in association with complex
      shoulder injuries. Isolated fractures of the coracoid process are uncommon. In
      the literature there is no consensus about the treatment. The conservative method
      is generally advocated. For better recognizing the particularities of coracoid
      anatomy and fracture-analysis we performed dissections on cadaver shoulders and
      also evaluated a useful radiologic technique for diagnosis. Between 1995 and 1997
      three patients with isolated displaced coracoid-fractures had open surgical
      repair. The postoperative course was very good in all three cases with complete
      recovery of shoulder function. DISCUSSION: We believe that isolated coracoid
      fractures with infero-lateral dislocation and loss of function should sustain
      open reduction and internal fixation with functional after treatment.

PMID- 9757812
TI  - [Basic principles in local dermatologic therapy].
AB  - The vehicle or ointment base plays an important role in dermatological local
      treatment. This is true from a therapeutic point of view and with respect to
      quality of life as well. Vehicles exert pronounced effects on the epidermis;
      these effects include hydration, lubrication, drying, skin smoothness, occlusion
      and protection. The vehicle controls the release and penetration, and ultimately
      the bioavailability, of the dermatological active ingredients. An overly
      simplified rule of thumb is that a deep-layer effect is enhanced by increasing
      occlusion. Unfortunately, no uniform classification system exists. Frequently,
      users of topical applied products are confused by the non-uniform, and in some
      cases erroneous, vehicle designations. In particular, different names are used to
      describe the lipophilic emulsion systems. It would be important to consistently
      use the official designations here: hydrophilic cream or lipophilic (hydrophobic)
      cream or ointment. Dermatological pastes are also often misleading designated,
      without any further distinctions, as a uniform occlusive system. For practical
      applications, attention must be paid in particular to the different indications
      for hydrophilic and lipophilic vehicles. Hydrophilic, aqueous bases are to be
      used for acute lesions and seborrhoeic skin, fatty or oily lipophilic systems for
      dry hyperkeratotic lesions and sebostatic skin. The cosmetic acceptance of a
      vehicle has a direct impact on both compliance and therapeutic effect. More
      attention should be paid to these factors. Adverse reactions caused by single
      components of the vehicle are not unusual. If a lesion does not respond to local
      treatment, the diagnosis should be reconsidered; moreover, the vehicle and its
      components should be investigated for possible incompatibility reactions.

PMID- 9757811
TI  - [Response of osteoblast cultures to titanium, steel and hydroxyapatite implants].
AB  - The biocompatibility of bone implants and substitutes is usually tested on cell
      lines only, despite a different and more relevant behaviour on primary
      osteoblasts as final targets can be expected. "Osteoblast-like" cell line (MC3T3
      E1) and fresh human osteoblasts (HOB), cultured from cancellous bone grafts from
      the iliac crest were used for the study. Three different clinically used
      biomaterials were compared regarding biocompatibility: titanium, steel and
      hydroxyapatite (Bio-Oss). "Osteoblast-like" cell line and fresh human osteoblasts
      (5x104) were seeded on the three bone implants. Cell proliferation and
      osteocalcin synthesis were determined 1, 3, 7, and 10 days after the cells were
      plated on the biomaterials. All experiments were performed in five times (pro
      culture double measurements). HOB proliferation on hydroxyapatite was decreasing
      after 3 days, whereas cells from "Osteoblast-like" cell line showed comparable
      proliferation to the control group. The most interesting observation was the
      significant decrease of the osteocalcin levels (in conditioned medium) of
      "osteoblast like" cells and HOB on HA (Bio-Oss). We conclude that HA disturbs the
      proliferation and osteocalcin synthesis of HOB.

PMID- 9757813
TI  - [Therapy of acne vulgaris].
AB  - Acne is an eminently curable disease. If therapeutic intervention sets in timely,
      scar formation can be prevented. Therapeutic modalities include the topical
      agents that should always be combined, and systemic agents, of which
      Isotretionoin is of particular importance. Isotretinoin is the only agent that
      can induce a complete clearing of acne lesions in 60 to 80% of cases. Adjuvant
      therapies, such as local injections, incisions, and peelings, are valuable tools
      in everyday practice and may accelerate the clearing of acne lesions. The
      treatment of acne is a long term endeavour that needs to be individually tuned to
      each patients' needs.

PMID- 9757814
TI  - [Psoriasis therapy today].
AB  - Psoriasis was already mentioned in the Corpus Hippocratium and only 1842 was it
      possible to separate this entity from lepromatous skin manifestations. Psoriasis
      is rather common and the prevalence in northern countries ranges between 1-2%.
      Psoriasis is an inherited disorder but the clinical manifestations depend on
      several triggers such as infections, drugs and stress. The clinical presentation
      is characterized by silvery scales on an erythematous ground. The management of
      psoriatic patients needs a broad experience. The objective degree of disease
      activity as well as the subjective aspects of the disease need to be taken in
      account. The therapeutic modalities used in the treatment of psoriasis can be
      compared with a symbolic ladder. At the beginning of the ladder emollients are to
      be mentioned. Ascending the ladder, different topical treatments can be used such
      as steroids or vitamin D and the more severe forms do need systemic treatments
      such as ultraviolet therapy, eventually combined with a photosensitizer,
      retinoids or methotrexate and even cyclosporine. In special cases treatment as an
      outpatient is not possible and then hospitalisation in a dermatologic unit is
      necessary.

PMID- 9757815
TI  - [Therapeutic management of neurodermatitis atopica].
AB  - The therapy of atopic dermatitis remains a challenge. The success of any
      therapeutic concept is based on a broad and early diagnostic approach which
      allows to rule out relevant provocation factors and allergens. During remission
      periods the regular use of a topical basic therapy consisting of drug-free
      emolients is recommended. Topical corticosteroids as well as systemic or local
      antimicrobial therapy and antihistamines are essential during periods of acute
      exacerbations. Although during the last years a great number of new therapeutic
      approaches have been published, data of most of these therapeutic modalities are
      not sufficient to allow an unrestricted use in all patients with atopic
      dermatitis.

PMID- 9757816
TI  - [Modern wart therapy].
AB  - A description of therapeutic modalities for the treatment of warts is given.
      Depending on localisation and types of warts, a variety of therapeutic modalities
      are available, which often will lead to eradication of the wart virus infection.
      It is important to choose therapies with low scarring potential.

PMID- 9757817
TI  - [Therapy of nail mycoses].
AB  - Onchomycosis is the most common nail disease, accounting for approximately 30% of
      all cutaneous fungal infections. The treatment approach needs to take into
      account the location and extent of onychomycosis, sensitivity of drug to fungal
      organism, adverse-effects profile, dosage schedule, duration of therapy,
      concomitant medical conditions, and concurrent medications. To confirm the
      diagnosis, it is important to correctly select the appropriate site for specimen
      collection used for both direct microscopy and fungal culture. Topical antifungal
      agents may be considered for the treatment of early onychomycosis, in the absence
      of nail matrix involvement. The newer generation of oral antifungal agents for
      the treatment of onychomycosis are terbinafine, itraconazole and fluconazole.
      These drugs used alone, or in combination with topical antifungals, are providing
      the basis for effective treatment of onychomycosis in a large proportion of
      patients.

PMID- 9757818
TI  - [Therapy of cutaneous melanoma].
AB  - Therapy of melanoma considers the individual prognosis. Primary low-risk
      melanomas with tumor-thickness below 1 mm can be treated by surgery with a safety
      margin of 1 cm. If the tumor-thickness is more than 2 mm the safety margin should
      be 3 cm. Elective lymph node dissection for melanomas at the extremities is
      widely substituted by the sentinel lymph node procedure. This new technique shall
      be applied only in specialised centers in the context of clinical trials. After
      the resection of lymph node metastases adjuvant treatment using Interferon-alpha
      should be considered. Palliative therapy of metastases includes surgery,
      radiotherapy and chemo-immunotherapy depending on the number and location of the
      metastases. Recent progress in understanding the immunobiology of melanoma and
      the development of gene therapy has offered new perspectives for future
      therapeutical intervention including peptide vaccination alone or loaded on
      dendritic cells and gene therapy.

PMID- 9757819
TI  - [Therapy of non-melanocytic skin tumors].
AB  - Actinic keratosis on sun-damaged skin are very common in individuals with fair
      complexion. Management encompasses cryosurgery, tretinoin or 5-fluorouracil
      cream. Bowen's disease, however, requires surgical excision or radiotherapy.
      Basal cell carcinoma and squamous cell carcinoma are the two most common
      malignant skin tumours in Western Europe. Typically these tumours can be managed
      either by excision and primary wound closure, by cryosurgery or by radiotherapy.
      The method of choice is determined by the type and location of the tumour and the
      general condition of the patient. For more difficult-to-treat malignant skin
      tumours surgical resection with histological margin control is required. Mohs'
      micrographic surgery is a specialized procedure. This method entails to a full
      work-up of the excisional margins. The defect is closed only after histological
      verification of tumour-free surgical margins. Difficult-to-treat tumours are
      recurrent, sclerodermiform and large (diameter more than 20 mm) basal cell
      carcinomas. Indications for margin control in squamous cell carcinomas are
      tumours with more than 20 mm of diameter, with more than 5 mm thickness and with
      poor histologic differentiation (Broders grade III and IV, desmoplastic squamous
      cell carcinoma). Therefore, a skin biopsy is often required to plan the optimal
      treatment of a malignant skin tumour. The collaboration of primary care providers
      and specialists is beneficial in the management of difficult skin tumours. Renal
      transplant recipients under immunosuppression are prone to have squamous cell
      carcinoma of a more aggressive type. Dermatofibrosarcoma protuberans is another
      good indication for Mohs' micrographic surgery. A regular follow-up for
      recurrences or secondary tumours, as well as an effective secondary prevention of
      sun damage are important for skin cancer patients.

PMID- 9757820
TI  - [Laser therapy in dermatology].
AB  - The use of lasers for cutaneous lesions has expanded rapidly since its inception
      in the early 1960s. The principle of selective photothermolysis dramatically
      improved the efficacy and safety of dermatologic laser systems. Selective
      photothermolysis is accomplished by choosing an appropriate wavelength and pulse
      duration. According to the target chromophores (hemoglobin, melanin and H2O),
      lasers may be grossly divided into 3 groups; systems to treat vascular lesions,
      pigmented lesions and the surgical lasers for skin ablation. Although vascular
      lesions can be treated with many lasers, the flash lamp pumped dye laser remains
      the laser of choice for port wine stains. Cw-lasers can treat telangiectases
      without purpura and are safer when used in conjunction with scanning devices. Q
      switched lasers have enhanced our ability to treat pigmented lesions, especially
      tattoos. The carbon dioxide laser remains the "workhorse" in dermatology. Safety
      and versatility are maximized when coupled with a scanning device or utilized in
      a high-powered, rapidly pulsed mode. Despite the expanding list of laser
      responsive lesions, other therapeutic modalities, sometimes at least equally
      effective and cheaper, must be carefully considered. This requires skill in
      dermatology and basic laser principles. Lasers add a substantial dimension in
      treating various skin disorders but are increasingly fraught with overuse.

PMID- 9757821
TI  - [Topical photodynamic therapy in dermatology].
AB  - Photodynamic therapy (PDT) is an experimental, noninvasive treatment of different
      malignant tumors. The principle is that applied photosensitizing substance
      selectively accumulate in neoplastic cells. Exposure to visible light then leads
      to the destruction of the tumor tissue. Following intravenous or oral
      administration of the photosensitizer (PS) generalised skin photosensitivity is
      the major side effect. Topical application of the PS under occlusive foil a novel
      method. Topical PDT (TPDT) is most investigated with 5-Aminolevulinic acid (ALA)
      as PS. ALA is a precursor of endogenous porphyrins in the biosynthetic pathway
      for heme. This new modality is increasingly and successfully used to treat
      precancerous and cancerous epithelial skin tumors, like actinic keratoses, basal
      cell carcinoma, squamous-cell carcinoma and Bowen disease. An other approach of
      ALA-TPDT are nontumoral applications, especially psoriasis. ALA-TPDT is well
      tolerated by patients and makes excellent cosmetic results. It is an alternative
      treatment for various superficial skin tumors.

PMID- 9757822
TI  - Novel homologs of replication protein A in archaea: implications for the
      evolution of ssDNA-binding proteins.
AB  - In Bacteria and Eukarya, ssDNA-binding proteins are central to most aspects of
      DNA metabolism. Until recently, however, no counterpart of an ssDNA-binding
      protein had been identified in the third domain of life, Archaea. Here, we report
      the discovery of a novel type of ssDNA-binding protein in the genomes of several
      archaeons. These proteins, in contrast to all known members of this protein
      family, possess four conserved DNA-binding sites within a single polypeptide or,
      in one case, two polypeptides. This peculiar structural organization allows us to
      propose a model for the evolution of this class of proteins.

PMID- 9757823
TI  - A unified DNA- and dNTP-binding mode for DNA polymerases.
AB  - Crystal structures of various DNA polymerases show a common structural topology
      that resembles a right hand and has distinct finger, palm and thumb subdomains.
      Early models of the klenow fragment (KF) of Escherichia coli polymerase I showed
      DNA entering a large cleft that faces the palm subdomain where the catalytic site
      is situated1,2. However, subsequent resolution of the structures of HIV-1 reverse
      transcriptase, KF and polymerase beta (pol beta) bound to DNA3-5 yielded
      conflicting data that suggested a different orientation for DNA bound to pol beta
      compared with DNA bound to other polymerases. The debate, on the correct
      orientation of the template-primer DNA, that followed failed to reach a
      consensus. Using an alternative superposition scheme, we now provide convincing
      evidence for a common DNA-binding mode that is applicable to all polymerases,
      including pol beta.

PMID- 9757825
TI  - Sensitive to the yoctomole limit.

PMID- 9757824
TI  - The FERM domain: a unique module involved in the linkage of cytoplasmic proteins
      to the membrane.

PMID- 9757826
TI  - A new family of phosphotransferases related to P-type ATPases.

PMID- 9757827
TI  - The HORMA domain: a common structural denominator in mitotic checkpoints,
      chromosome synapsis and DNA repair.

PMID- 9757828
TI  - A superfamily of proteins that contain the cold-shock domain.
AB  - Members of a family of cold-shock proteins (CSPs) are found throughout the
      eubacterial domain and appear to function as RNA-chaperones. They have been
      implicated in various cellular processes, including adaptation to low
      temperatures, cellular growth, nutrient stress and stationary phase. The
      discovery of a domain--the cold-shock domain--that shows strikingly high homology
      and similar RNA-binding properties to CSPs in a growing number of eukaryotic
      nucleic-acid-binding proteins suggests that these proteins have an ancient
      origin.

PMID- 9757829
TI  - The INK4a/ARF tumor suppressor: one gene--two products--two pathways.
AB  - Functional inactivation of the retinoblastoma (RB) and p53 pathways appears to be
      a rite of passage for all cancerous cells and results in disruption of cell-cycle
      regulation and deactivation of the apoptotic response that normally ensues. The
      INK4a/ARF locus sits at the nexus of these two growth-control pathways, by virtue
      of its ability to generate two distinct products: the p16INK4a protein, a cyclin
      dependent kinase inhibitor that functions upstream of RB; and the p19ARF protein,
      which blocks MDM2 inhibition of p53 activity. This 'one gene--two products--two
      pathways' arrangement provides a basis for the prominence of INK4a/ARF in
      tumorigenesis.

PMID- 9757830
TI  - Nucleic-acid-chaperone activity of retroviral nucleocapsid proteins: significance
      for viral replication.
AB  - Retrovirus particles contain a small, basic protein, the nucleocapsid (NC)
      protein, that possesses 'nucleic acid chaperone' activity--that is, the NC
      protein can catalyze the rearrangement of a nucleic acid molecule into the
      conformation that has the maximal number of base pairs. The molecular mechanism
      that underlies this effect is not understood. Because the chaperone activity is
      apparently crucial during the infectious process, NC is a potential target for
      antiviral therapy.

PMID- 9757832
TI  - MAPs, MARKs and microtubule dynamics.
AB  - Microtubules (MTs) serve as tracks for cellular transport, and regulate cell
      shape and polarity. Rapid transitions between stable and dynamic forms of MTs are
      central to these processes. This dynamic instability is regulated by a number of
      cellular factors, including the structural MT-associated proteins (MAPs), which
      in turn are regulated by phosphorylation. MT-affinity-regulating kinases (MARKs)
      are novel mammalian serine/threonine kinases that phosphorylate the tubulin
      binding domain of MAPs and thereby cause their detachment from MTs and increased
      MT dynamics. Molecular cloning of MARKs revealed a family of four closely related
      protein kinases that share homology with genes from the nematode Caenorhabditis
      elegans and fission yeast that are involved in the generation of cell shape and
      polarity. Hence, MARKs might play a role in the regulation of MT stability during
      morphogenesis.

PMID- 9757833
TI  - Forty years under the central dogma.

PMID- 9757831
TI  - Gathering STYX: phosphatase-like form predicts functions for unique protein
      interaction domains.
AB  - The effects of tyrosine phosphorylation are manifested and regulated through
      protein domains that bind to specific phosphotyrosine motifs. STYX is a unique
      modular domain found within proteins implicated in mediating the effects of
      tyrosine phosphorylation in vivo. Individual STYX domains are not catalytically
      active; however, they resemble protein tyrosine phosphatase (PTP) domains and,
      like PTPs, contain core sequences that recognize phosphorylated substrates. Thus,
      the STYX domain adds to the repertoire of modular domains that can mediate
      intracellular signaling in response to protein phosphorylation.

PMID- 9757834
TI  - Girls' and boys' differing response to pain starts early in their lives.

PMID- 9757835
TI  - Tragic loss of leaders in AIDS and public health.

PMID- 9757836
TI  - Unacceptable nursing home deaths unautopsied.

PMID- 9757837
TI  - Washington marchers unite to conquer cancer.

PMID- 9757839
TI  - From the Centers for Disease Control and Prevention. Maternal mortality--United
      States, 1982-1996.

PMID- 9757838
TI  - Challenging report on pregnancy and drug abuse.

PMID- 9757840
TI  - From the Centers for Disease Control and Prevention. Recommendations of the
      Advisory Committee on Immunization Practices, the American Academy of Pediatrics,
      and the American Academy of Family Physicians: use of reminder and recall by
      vaccination providers to increase vaccination rates.

PMID- 9757841
TI  - President's address. Packing my bag for the road ahead.

PMID- 9757842
TI  - Diagnosis, treatment, and prevention of Lyme disease.

PMID- 9757843
TI  - Diagnosis, treatment, and prevention of Lyme disease.

PMID- 9757844
TI  - Diagnosis, treatment, and prevention of Lyme disease.

PMID- 9757845
TI  - Diagnosis, treatment, and prevention of Lyme disease.

PMID- 9757846
TI  - The ungifted physician.

PMID- 9757847
TI  - The ungifted physician.

PMID- 9757848
TI  - The ungifted physician.

PMID- 9757849
TI  - Physician recommendations vs insurance coverage for growth hormone.

PMID- 9757850
TI  - Physician recommendations vs insurance coverage for growth hormone.

PMID- 9757851
TI  - Physician recommendations vs insurance coverage for growth hormone.

PMID- 9757852
TI  - Importance of hemodynamic factors in the prognosis of symptomatic carotid
      occlusion.
AB  - CONTEXT: The relative importance of hemodynamic factors in the pathogenesis and
      treatment of stroke in patients with carotid artery occlusion remains
      controversial. OBJECTIVE: To test the hypothesis that stage II cerebral
      hemodynamic failure (increased oxygen extraction measured by positron emission
      tomography [PET]) distal to symptomatic carotid artery occlusion is an
      independent risk factor for subsequent stroke in medically treated patients.
      DESIGN AND SETTING: Prospective, blinded, longitudinal cohort study of patients
      referred from a group of regional hospitals between 1992 and 1996. PATIENTS: From
      419 subjects referred, 81 with previous stroke or transient ischemic attack in
      the territory of an occluded carotid artery were enrolled. All were followed up
      to completion of the study, with average follow-up of 31.5 months. MAIN OUTCOME
      MEASURES: Telephone contact every 6 months recorded the subsequent occurrence of
      all stroke, ipsilateral ischemic stroke, and death. RESULTS: Stroke occurred in
      12 of 39 patients with stage II hemodynamic failure and in 3 of 42 patients
      without (P = .005); stroke was ipsilateral in 11 of 39 patients with stage II
      hemodynamic failure and in 2 of 42 patients without (P = .004). Six deaths
      occurred in each group (P = .94). The age-adjusted relative risk conferred by
      stage II hemodynamic failure was 6.0 (95% confidence interval [CI], 1.7-21.6) for
      all stroke and 7.3 (95% CI, 1.6-33.4) for ipsilateral stroke. CONCLUSIONS: Stage
      II hemodynamic failure defines a subgroup of patients with symptomatic carotid
      occlusion who are at high risk for subsequent stroke when treated medically. A
      randomized trial evaluating surgical revascularization in this high-risk subgroup
      is warranted.

PMID- 9757853
TI  - Low-dose hydrocortisone for treatment of chronic fatigue syndrome: a randomized
      controlled trial.
AB  - CONTEXT: Chronic fatigue syndrome (CFS) is associated with a dysregulated
      hypothalamic-pituitary adrenal axis and hypocortisolemia. OBJECTIVE: To evaluate
      the efficacy and safety of low-dose oral hydrocortisone as a treatment for CFS.
      DESIGN: A randomized, placebo-controlled, double-blind therapeutic trial,
      conducted between 1992 and 1996. SETTING: A single-center study in a tertiary
      care research institution. PATIENTS: A total of 56 women and 14 men aged 18 to 55
      years who met the 1988 Centers for Disease Control and Prevention case criteria
      for CFS and who withheld concomitant treatment with other medications.
      INTERVENTION: Oral hydrocortisone, 13 mg/m2 of body surface area every morning
      and 3 mg/m2 every afternoon, or placebo, for approximately 12 weeks. MAIN OUTCOME
      MEASURES: A global Wellness scale and other self-rating instruments were
      completed repeatedly before and during treatment. Resting and cosyntropin
      stimulated cortisol levels were obtained before and at the end of treatment.
      Patients recorded adverse effects on a checklist. RESULTS: The number of patients
      showing improvement on the Wellness scale was 19 (54.3%) of 35 placebo recipients
      vs 20 (66.7%) of 30 hydrocortisone recipients (P =.31). Hydrocortisone recipients
      had a greater improvement in mean Wellness score (6.3 vs 1.7 points; P=.06), a
      greater percentage (53% vs 29%; P=.04) recording an improvement of 5 or more
      points in Wellness score, and a higher average improvement in Wellness score on
      more days than did placebo recipients (P<.001). Statistical evidence of
      improvement was not seen with other self-rating scales. Although adverse symptoms
      reported by patients taking hydrocortisone were mild, suppression of adrenal
      glucocorticoid responsiveness was documented in 12 patients who received it vs
      none in the placebo group (P<.001). CONCLUSIONS: Although hydrocortisone
      treatment was associated with some improvement in symptoms of CFS, the degree of
      adrenal suppression precludes its practical use for CFS.

PMID- 9757854
TI  - Prevention of estrogen deficiency-related bone loss with human parathyroid
      hormone-(1-34): a randomized controlled trial.
AB  - CONTEXT: Short-term intermittent administration of parathyroid hormone (PTH)
      prevents bone loss from the spine in women treated with a gonadotropin-releasing
      hormone (GnRH) analog. However, the effects of a longer period of PTH
      administration on bone mass in estrogen-deficient women, particularly on the hip
      and on cortical bone of the total body, are unknown. OBJECTIVE: To determine
      whether more prolonged PTH administration can prevent estrogen deficiency bone
      loss from the hip, spine, and total body in young women with endometriosis
      receiving GnRH analog (nafarelin acetate) therapy. DESIGN: Randomized controlled
      trial. SETTING: General Clinical Research Center of a tertiary care, university
      affiliated hospital. PATIENTS: Forty-three women between the ages of 21 and 45
      years with symptomatic endometriosis. INTERVENTION: Nafarelin alone (200 microg
      intranasally twice daily) or nafarelin plus human parathyroid hormone-(1-34)
      (hPTH-[1-34]) (40 microg subcutaneously daily). MAIN OUTCOME MEASURES: The
      primary end points were bone mineral density (BMD) of the anterior-posterior and
      lateral spine, femoral neck, trochanter, radial shaft, and total body at 12
      months of treatment. RESULTS: In the women who received nafarelin alone, the mean
      (SEM) BMDs of the anterior-posterior spine, lateral spine, femoral neck,
      trochanter, and total body were 4.9% (0.6%) (P<.001), 4.9% (0.8%) (P<.001), 4.7%
      (1.1%) (P<.001), 4.3% (0.9%) (P<.001), and 2.0% (0.6%) (P= .003) lower than at
      baseline after 12 months of therapy. In contrast, coadministration of hPTH-(1-34)
      increased BMD of the anterior-posterior spine by 2.1% (1.1%) (P=.09) and lateral
      spine by 7.5% (1.9%) (P=.002) and prevented bone loss from the femoral neck,
      trochanter, and total body, despite severe estrogen deficiency. Radial shaft BMD
      did not change significantly in either group. Serum bone-specific alkaline
      phosphatase and osteocalcin concentrations and urinary excretion of
      hydroxyproline and deoxypyridinoline increased 2-fold to 3-fold during the first
      6 to 9 months of therapy in the women who received nafarelin plus hPTH-(1-34) and
      then declined. Changes in urinary deoxypyridinolone excretion were strongly
      predictive (r= 0.85) of changes in spinal BMD in the women who received nafarelin
      plus hPTH-(1-34). CONCLUSIONS: Parathyroid hormone prevents bone loss from the
      proximal femur and total body and increases lumbar spinal BMD in young women with
      GnRH analog-induced estrogen deficiency.

PMID- 9757855
TI  - Modulation of abnormal colonic epithelial cell proliferation and differentiation
      by low-fat dairy foods: a randomized controlled trial.
AB  - CONTEXT: Before the development of human colonic neoplasms, colonic epithelial
      cells showed altered growth and differentiation. These alterations characterized
      mucosa at risk for cancer formation and were termed intermediate biomarkers of
      risk. Modifications of the mucosa toward more normal features by nutrients or
      drugs are putative approaches to chemoprevention of colon cancer. OBJECTIVE: To
      determine whether increasing calcium intake via dairy products alters colonic
      biomarkers toward normal. DESIGN: Randomized, single-blind, controlled study.
      SETTING: Outpatient clinic. PARTICIPANTS: Seventy subjects with a history of
      polypectomy for colonic adenomatous polyps. INTERVENTION: Low-fat dairy products
      containing up to 1200 mg/d of calcium. Subjects were randomized to 4 strata by
      diet (control vs higher calcium) and age (<60 vs > or = 60 years). MAIN OUTCOME
      MEASURES: Changes in total colonic epithelial cells and number and position of
      thymidine-labeled epithelial cells and changes in the ratio of sulfomucins
      (predominantly secreted by distal colorectal epithelial cells) to sialomucins and
      expression of cytokeratin AE1, 2 markers of colonic cell differentiation.
      RESULTS: During 6 and 12 months of treatment, reduction of colonic epithelial
      cell proliferative activity (P<.05), reduction in size of the proliferative
      compartment (P<.05), and restoration of acidic mucin (P<.02), cytokeratin AE1
      distribution (P<.05), and nuclear size (P<.05) toward that of normal cells
      occurred. Control subjects showed no differences from baseline proliferative
      values at 6 and 12 months (P>.05). CONCLUSION: Increasing the daily intake of
      calcium by up to 1200 mg via low-fat dairy food in subjects at risk for colonic
      neoplasia reduces proliferative activity of colonic epithelial cells and restores
      markers of normal cellular differentiation.

PMID- 9757857
TI  - A 55-year-old man with attention-deficit/hyperactivity disorder.

PMID- 9757858
TI  - A 73-year-old man with symptomatic benign prostatic hyperplasia, 1 year later.

PMID- 9757856
TI  - False-positive HIV-1 test results in a low-risk screening setting of voluntary
      blood donation. Retrovirus Epidemiology Donor Study.
AB  - CONTEXT: Persons at risk of human immunodeficiency virus 1 (HIV-1) infection,
      have been classified incorrectly as HIV infected because of Western blot results,
      but the frequency of false-positive Western blot results is unknown. OBJECTIVES:
      To determine the frequency of false-positive HIV-1 Western blot results in US
      blood donors and to make projections to other screened populations. Secondarily,
      to validate an algorithm for evaluating possible false-positive cases. DESIGN: A
      retrospective cohort study of HIV-1 enzyme immunoassay (EIA) and Western blot
      results from large blood donor screening programs in which donors with suspected
      false-positive Western blot results underwent HIV-1 RNA polymerase chain reaction
      (PCR) testing and follow-up HIV-1 serology. SETTING: Five US blood centers
      participating in the Retrovirus Epidemiology Donor Study. PARTICIPANTS: More than
      5 million allogeneic and autologous blood donors who successfully donated blood
      at 1 of the 5 participating centers from 1991 through 1995. MAIN OUTCOME
      MEASURES: Rate of false positivity by Western blot and true HIV-1 infection
      status as determined by HIV-1 RNA PCR and by serologic follow-up of blood donors
      more than 5 weeks after donation. RESULTS: Of 421 donors who were positive for
      HIV-1 by Western blot, 39 (9.3%) met the criteria of possible false positivity
      because they lacked reactivity to p31. Of these, 20 (51.3%) were proven by PCR
      not to be infected with HIV-1. The false-positive prevalence was 4.8% of Western
      blot-positive donors and 0.0004% (1 in 251000) of all donors (95% confidence
      interval, 1 in 173000 to 1 in 379000 donors). CONCLUSIONS: A false diagnosis of
      HIV-1 infection can result from the combination of EIA and Western blot testing
      in blood donor and other HIV-1 screening programs. Individuals with a positive
      Western blot result lacking the p31 band should be counseled that, although they
      may be HIV infected, there is uncertainty about this conclusion. These
      individuals should be further evaluated by RNA PCR testing (if feasible) and HIV
      serologic analysis on a follow-up sample.

PMID- 9757859
TI  - Occlusion of the internal carotid artery: reopening a closed door?

PMID- 9757860
TI  - The nature of chronic fatigue.

PMID- 9757861
TI  - Proliferation happens.

PMID- 9757862
TI  - Two tiers of physicians in France: general pediatrics declines, general practice
      rises.

PMID- 9757864
TI  - JAMA patient page: stroke.

PMID- 9757863
TI  - Physicians as double agents: maintaining trust in an era of multiple
      accountabilities.

PMID- 9757865
TI  - Genetic risks of intracytoplasmic sperm injection in the treatment of male
      infertility: recommendations for genetic counseling and screening.
AB  - OBJECTIVE: To review the most clinically significant genetic disorders associated
      with severe oligospermia and azoospermia in males, and to present recommendations
      for the genetic counseling and screening of infertile males and their partners
      before undertaking intracytoplasmic sperm injection (ICSI)-assisted reproduction.
      DESIGN: The literature on genetic disorders associated with severe oligospermia
      and azoospermia was reviewed, and the most recent outcome data from surveys of
      ICSI-derived offspring are presented. Studies related to this topic were
      identified through MEDLINE. RESULT(S): Genetic disorders are not infrequent
      causes of severe oligospermia and azoospermia in males undergoing ICSI-assisted
      reproduction. The application of ICSI in the treatment of oligospermic or
      azoospermic males may result in the transmission or de novo introduction of
      genetic mutations or chromosomal abnormalities in their offspring. Genetic
      counseling and appropriate screening of couples with male infertility should be
      performed before their undertaking ICSI-assisted reproduction. CONCLUSIONS: An
      understanding of the genetic risks and possible consequences that are inherent
      when ICSI is used to assist fertilization in couples with male infertility is
      necessary for clinicians and their patients.

PMID- 9757866
TI  - Genetic counseling for patients who will be undergoing treatment with assisted
      reproductive technology.

PMID- 9757867
TI  - Shared-risk or refund programs in assisted reproduction. The Ethics Committee of
      the American Society for Reproductive Medicine.

PMID- 9757868
TI  - The ethics of guaranteeing patient outcomes.

PMID- 9757869
TI  - Ethics of guaranteeing patient outcomes: a complex issue whose time has not come.

PMID- 9757870
TI  - The follicular and endocrine environment in women with endometriosis: local and
      systemic cytokine production.
AB  - OBJECTIVE: To assess the endocrine, paracrine, and autocrine milieu in patients
      with endometriosis on the basis of the measurement of several cytokines in serum
      and follicular fluid (FF) and in vitro culture of granulosa luteal cells. DESIGN:
      Case-control study. SETTING: In vitro fertilization program at the Instituto
      Valenciano de Infertilidad. PATIENT(S): Twenty patients with laparoscopically
      documented endometriosis and 18 controls. Fifteen subjects were studied in a
      natural cycle and 23 were investigated in a stimulated cycle while undergoing
      IVF. INTERVENTION(S): Individual follicle aspiration, oocyte isolation, FF
      storage, and preparation of luteinized granulosa cell cultures. Diagnostic
      laparoscopy in natural cycles. MAIN OUTCOME MEASURE(S): Serum (day of ovum pick
      up or laparoscopy) and FF measurement of interleukin (IL)-1beta, IL-6, and
      vascular endothelial growth factor (VEGF). Secretion of IL-1beta, IL-6, and VEGF
      in the cell-conditioned medium. Results were compared between patients with
      endometriosis and controls. RESULT(S): Interleukin-6 levels in serum were
      increased in the natural cycles of patients with endometriosis and modulated by
      ovarian stimulation, showing a significant decrease in hMG- and FSH-stimulated
      cycles and a significant increase after hCG administration. In addition, IL-6
      levels were increased in the FF of patients with endometriosis and released in
      higher amounts by their granulosa luteal cells. Vascular endothelial growth
      factor was accumulated in lesser concentrations in the FF of patients with
      endometriosis. Interleukin-1beta levels did not show significant changes.
      Implantation rates were decreased significantly in patients with endometriosis
      who were undergoing IVF. CONCLUSION(S): The data demonstrate that cytokines are
      regulated differently in patients with endometriosis, who have increased IL-6
      production, and suggest that fine hormonal modulation of this cytokine occurs at
      the systemic and local (ovarian) levels. These changes show that the endocrine,
      paracrine, and autocrine milieu is different in patients with endometriosis and
      may be related to their lower implantation rates.

PMID- 9757871
TI  - A prospective study of reproductive factors and oral contraceptive use in
      relation to the risk of uterine leiomyomata.
AB  - OBJECTIVE: To investigate the risk of uterine leiomyomata in relation to
      reproductive factors and oral contraceptive use. DESIGN: A prospective study.
      SETTING: A cohort of female registered nurses from 14 states in the United States
      who completed mailed questionnaires in 1989, 1991, and 1993. PATIENT(S):
      Premenopausal nurses (n=95,061) aged 25-42 years with intact uteri and no history
      of diagnosed uterine leiomyomata or cancer in 1989. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Incidence of self-reported uterine leiomyomata confirmed by
      ultrasound or hysterectomy. In a sample of 243 cases, 93% of the self-reported
      diagnoses were confirmed in the medical record. RESULT(S): During 326,116 person
      years of follow-up, 3,006 cases of uterine leiomyomata, confirmed by ultrasound
      or hysterectomy, were reported. After adjustment for other risk factors, the risk
      of uterine leiomyomata was significantly inversely associated with age at
      menarche, parity, and age at first birth, and positively associated with a
      history of infertility and years since last birth. The only notable association
      with any aspect of oral contraceptive use was a significantly elevated risk among
      women who first used oral contraceptives at ages 13-16 years compared with those
      who had never used oral contraceptives. CONCLUSION(S): Reproductive factors and
      oral contraceptive use at a young age influence the risk of uterine leiomyomata
      among premenopausal women.

PMID- 9757872
TI  - Reproductive sequelae in female rats after in utero and neonatal exposure to the
      phytoestrogen genistein.
AB  - OBJECTIVE: To determine reproductive sequelae in female rats after in utero and
      lactational dietary exposure to genistein. DESIGN: Experimental animal study.
      SETTING: University laboratory. ANIMAL(S): Sprague Dawley rats. INTERVENTION(S):
      Pregnant rats were fed control rat chow or rat chow incorporated with genistein
      (approximately 50 microg/d) beginning on day 17 of gestation and continuing until
      the end of lactation (postpartum day 21). Genistein-exposed female pups were
      divided into two groups on day 21. One group continued to receive a genistein
      added diet (G70); the other group was changed to a control diet (Ex-G). At
      necropsy (days 21 and 70), blood and reproductive tissues were collected. MAIN
      OUTCOME MEASURE(S): Serum levels of gonadotropins and gonadal steroids and
      histopathologic examination of the ovaries. RESULT(S): The weight of the ovaries
      and uterus and serum levels of E2 and progesterone in genistein-exposed rats on
      day 21 (G21) were significantly reduced compared with control rats. On day 70,
      serum levels of E2, progesterone, LH, and FSH were similar in all groups. Atretic
      follicles and secondary interstitial glands were more common in G70 and Ex-G rats
      compared with control rats. Cystic rete ovarii was observed in some G70 and Ex-G
      rats. CONCLUSION(S): Our data indicate that in utero and lactational exposure to
      dietary genistein adversely affects reproductive processes in the adult female
      rat.

PMID- 9757873
TI  - The World Health Organization Multinational Study of Breast-feeding and
      Lactational Amenorrhea. I. Description of infant feeding patterns and of the
      return of menses. World Health Organization Task Force on Methods for the Natural
      Regulation of Fertility.
AB  - OBJECTIVE: To detect differences between populations in both infant feeding
      practices and the duration of lactational amenorrhea, if they exist. DESIGN:
      Prospective, nonexperimental, longitudinal follow-up study. SETTING: Five
      developing and two developed countries. PATIENT(S): Four thousand one hundred
      eighteen breast-feeding mothers and their infants. INTERVENTION(S): Breast
      feeding women collected ongoing information about infant feeding and family
      planning practices, plus the return of menses. Fortnightly follow-up occurred in
      the women's homes. MAIN OUTCOME MEASURE(S): Breast-feeding frequency by day (and
      by night); 24-hour breast-feeding duration, percent of all infant feedings that
      were milk/milk-based (and solid/semisolid foods); time until the end of full
      breast-feeding; time until regular supplementation; and time until the end of
      lactational amenorrhea. RESULT(S): Differences between the centers in the
      duration of amenorrhea were substantial, ranging from a median of 4 months in New
      Delhi (India) to 9 months in Chengdu (China). Women in developed countries (but
      also women in Chengdu) were more likely to delay supplementation (for up to 5
      months), whereas women in Santiago (Chile), Guatemala City (Guatemala), and
      Sagamu (Nigeria) started supplements much earlier, sometimes as early as 1 week
      after birth. CONCLUSION(S): Both breast-feeding behavior and the duration of
      lactational amenorrhea vary markedly across settings, indicating that breast
      feeding promotion and family planning advice should be site- and culture
      specific.

PMID- 9757874
TI  - The World Health Organization Multinational Study of Breast-feeding and
      Lactational Amenorrhea. II. Factors associated with the length of amenorrhea.
      World Health Organization Task Force on Methods for the Natural Regulation of
      Fertility.
AB  - OBJECTIVE: To determine the relation between infant feeding practices (and other
      factors) and the duration of postpartum amenorrhea, and to establish whether
      there are real differences in the duration of postpartum amenorrhea for similar
      breast-feeding practices in different populations. DESIGN: Prospective,
      nonexperimental, longitudinal follow-up study. SETTING: Five developing and two
      developed countries. PATIENT(S): Four thousand one hundred eighteen breast
      feeding mothers and their infants. INTERVENTION(S): Breast-feeding women
      collected ongoing information about infant feeding and family planning practices,
      plus the return of menses. Fortnightly follow-up occurred in the women's homes.
      MAIN OUTCOME MEASURE(S): A multivariate analysis explored the association between
      the risk of menses return and 16 infant feeding variables and 11 other
      characteristics. RESULT(S): Ten factors (in addition to center effects) were
      significantly related to the duration of amenorrhea. Seven of these were infant
      feeding characteristics and the remaining three were high parity, low body mass
      index, and a higher frequency of infant illness. CONCLUSION(S): The breast
      feeding stimulus is strongly linked to the duration of postpartum amenorrhea.
      Cross-cultural effects also are extremely important and may have caused the
      variations in feeding, the variation in amenorrhea, or both.

PMID- 9757875
TI  - Serum leptin concentration in women: effect of age, obesity, and estrogen
      administration.
AB  - OBJECTIVE: To compare serum leptin levels in normally cycling reproductive
      females (20-35 years old) with those in age-matched males, in women who were
      receiving oral contraceptives, and in older (postmenopausal) women (50-65 years
      old) who were or who were not receiving hormone replacement therapy. DESIGN: Case
      control study. SETTING: Obstetrics and Gynecology Clinic, Texas Tech University
      Health Sciences Center-Amarillo, or the Exercise Physiology Laboratory at
      Southeastern Louisiana University. PATIENT(S): Normally cycling women between the
      ages of 20-35 years and age-matched controls who were receiving oral
      contraceptives. Postmenopausal women between the ages of 50-65 years who were or
      who were not receiving hormone replacement therapy. MAIN OUTCOME MEASURE(S):
      Serum leptin concentration. RESULT(S): In all groups, serum leptin concentrations
      were correlated significantly with body mass index. Leptin levels were
      significantly higher in young women than young men (P <.001), but no other
      statistically significant differences were found for the other three comparisons.
      CONCLUSION(S): Serum leptin concentrations expressed as a measure of adiposity
      (body mass index) are greater in young normally cycling females (20-35 years old)
      than in age-matched males. There is no difference in levels of serum leptin
      between young and postmenopausal (50-65 years old) women. Estrogen
      administration, either in young women who are receiving estrogen-progestin oral
      contraceptives or in postmenopausal women who are receiving hormone replacement
      therapy, does not effect serum leptin concentrations.

PMID- 9757876
TI  - Probabilities for singleton and multiple pregnancies after in vitro
      fertilization.
AB  - OBJECTIVE: To help physicians provide risk estimates for specific pregnancy
      outcomes. DESIGN: Computation of exact binomial probabilities for singleton and
      multiple pregnancies as a function of two inputs: the number of embryos
      transferred and the implantation rate. Inputs were varied over the range of
      values reported in the literature. MAIN OUTCOME MEASURE(S): Probabilities for a
      singleton pregnancy (none), a multiple pregnancy (Pmult), and no pregnancy
      (Pnone) after one IVF cycle. RESULT(S): Given a 30% implantation rate and three
      embryos transferred, Pone=.44, Pmult=.22, and Pnone=.34. Although further
      increasing the number of embryos transferred increases the chance of pregnancy,
      it also raises the probability of a multiple pregnancy and lowers the chance of a
      singleton pregnancy. Although varying the implantation rate changes the specific
      probability estimates, the same trade-off persists. CONCLUSION(S): Those who
      consider an IVF "success" to be a singleton pregnancy should be attentive to the
      number of embryos transferred. Infertility therapy may be one area in medicine
      where more is not necessarily better.

PMID- 9757877
TI  - Mannose ligand receptor assay as a test to predict fertilization in vitro: a
      prospective study.
AB  - OBJECTIVE: To assess whether mannose receptor assays can predict fertilization
      outcome in vitro. DESIGN: A prospective, double-blind study of the mannose
      receptor properties of spermatozoa. SETTING: Assisted human reproduction program
      at a university hospital. PATIENT(S): Partners of 140 consecutive women
      undergoing their first in vitro fertilization cycle. INTERVENTION(S): Motile
      sperm populations were tested for surface receptors for mannose by measuring
      their ability to bind fluorescein-labeled mannosylated albumin and to undergo a
      free mannose-induced acrosome reaction as judged by Pisum, sativum agglutinin
      binding. MAIN OUTCOME MEASURE(S): Mannose receptor assay results were correlated
      with fertilization outcomes using several statistical tests, including the chi2
      test, chi2 for proportions, t-tests, analysis of variance with Student-Newman
      Keuls tests and correlational and receiver operating characteristic (ROC) curve
      analysis. RESULT(S): The fractional increment increase on incubation in the
      percent of sperm binding mannose ligand over an intact acrosome correlated with
      fertilization rates in vitro. Threshold values of mannose ligand binding and of
      mannose-induced acrosome reactions predictive of fertilization rates were
      identified by ROC curve analysis. Men were thus classified into one of four
      groups with differing fertilization rates in vitro. CONCLUSION(S): The increment
      increase in sperm surface mannose ligand binding by acrosome-intact sperm
      correctly predicts high and low fertilization rates in vitro and identifies cases
      where conventional insemination can result in failed fertilization.

PMID- 9757878
TI  - Adverse effects of hydrosalpinx on pregnancy rates after in vitro fertilization
      embryo transfer.
AB  - OBJECTIVE: To determine the effect of hydrosalpinx on the establishment of
      pregnancy after IVF-ET. DESIGN: Metaanalysis. SETTING: University medical center.
      PATIENT(S) AND INTERVENTION(S): All published reports (n=13) and abstracts (n=10)
      in English that examined the relation between hydrosalpinx and IVF-ET were
      included in the analysis. The metaanalysis was performed by first calculating the
      odds ratios for each trial and then combining them to obtain a pooled estimate of
      the odds ratio and a 95% confidence interval. MAIN OUTCOME MEASURE(S): Clinical
      pregnancy. RESULT(S): A total of 5,569 cycles was reviewed in the group without
      hydrosalpinx, and a total of 1,144 was reviewed in the group with hydrosalpinx.
      The clinical pregnancy rate was approximately 50% lower in patients who had
      hydrosalpinx. Similarly, the implantation rate was decreased by 50%. These
      effects were observed also in thawed ET cycles. The abortion rate was more than
      twofold higher in patients who had hydrosalpinx. CONCLUSION(S): This metaanalysis
      suggests that hydrosalpinx is associated with a reduced chance of implantation
      and an increased risk of pregnancy loss.

PMID- 9757879
TI  - Outcome of pregnancies after intracytoplasmic sperm injection and the effect of
      sperm origin and quality on this outcome.
AB  - OBJECTIVE: To describe the outcome of pregnancies obtained after intracytoplasmic
      sperm injection (ICSI) and the impact of the origin and quality of sperm used on
      this outcome. DESIGN: Retrospective analysis. SETTING: A tertiary referral center
      for assisted reproduction. PATIENT(S): Pregnant patients conceived after
      microinjection of ejaculated sperm (n=1,427), epididymal sperm (n=79), and
      testicular sperm (n=93). INTERVENTION(S): ICSI, epididymal sperm aspiration, and
      testicular biopsy. MAIN OUTCOME MEASURE(S): Stillbirth, prematurity, and early
      perinatal mortality. RESULT(S): The delivery rate of multiple births was 31.4%,
      and the preterm delivery rate was 25.6%. The prematurity rates in singletons,
      twins, and triplets were 9.9%, 56.7%, and 96.6%, respectively. The early
      perinatal mortality rate of the entire population was 26.1 per thousand. In the
      ejaculated-sperm group, when the sperm was severely defective (group 1), 14
      intrauterine deaths occurred (3.1%). In the second and third groups, in which
      sperm was moderately defective, there were 2 deaths and 1 death (0.6% and 0.4%),
      respectively. The difference between the number of deaths in group 1 vs. groups
      2/3 was statistically significant. CONCLUSION(S): The rates of multiple
      pregnancies, preterm deliveries, low birth weight, and early perinatal mortality
      were higher after ICSI than after natural conception. In the ejaculated-sperm
      group, the rate of intrauterine death was higher in the severely defective sperm
      group than in the better-quality sperm groups.

PMID- 9757880
TI  - Prevalence of Y chromosome microdeletions in oligospermic and azoospermic
      candidates for intracytoplasmic sperm injection.
AB  - OBJECTIVE: To determine the prevalence and type of Y chromosome microdeletions in
      136 consecutively seen intracytoplasmic sperm injection (ICSI) candidates and in
      50 consecutively seen azoospermic men attending an infertility clinic. DESIGN:
      Controlled clinical study. SETTING: Genetics laboratory and infertility clinic at
      a University hospital. PATIENT(S): One hundred eighty-six men who were seen at an
      infertility clinic and who were referred to a genetics counseling service for
      genetic assessment before ICSI. INTERVENTION(S): Collection of semen and blood
      samples. MAIN OUTCOME MEASURE(S): Semen analysis; serum FSH, LH, and T levels;
      karyotype analysis; and presence or absence of several single tagged site markers
      along the Y chromosome (sY274, sY238, sY276, sY84, sY102, sY143, sY153, sY254,
      sY269, sY202, sY158, sY160). RESULT(S): Yq chromosome microdeletions were
      detected in 10 (5.4%) of 186 consecutively seen ICSI candidates. The number of
      microdeletions was much higher in azoospermic patients (16%; 8 of 50) than in
      oligospermic patients (1.5%; 2 of 136). Two of the azoospermic patients with a Yq
      microdeletion also had sex chromosome aneuploidy mosaicism. No microdeletions
      were detected in 100 consecutively seen fathers who were included as controls.
      CONCLUSION(S): The prevalence of Yq microdeletions in the azoospermic group was
      much higher than in the oligospermic group and was consistent with the prevalence
      of Yq microdeletions detected in other series of azoospermic men in different
      geographic areas. All Yq microdeletions found in our patients belong to the AZFc
      region, indicating that microdeletions of the AZFa and AZFb regions are
      infrequent among oligospermic ICSI candidates or azoospermic males in our
      population.

PMID- 9757881
TI  - Systemic methotrexate therapy versus laparoscopic salpingostomy in patients with
      tubal pregnancy. Part I. Impact on patients' health-related quality of life.
AB  - OBJECTIVE: To compare patients' health-related quality of life after systemic
      methotrexate therapy versus laparoscopic salpingostomy for tubal pregnancy.
      DESIGN: Multicenter randomized clinical trial. SETTING: Departments of obstetrics
      and gynecology of six Dutch hospitals. PATIENT(S): Hemodynamically stable
      patients with a laparoscopically confirmed unruptured tubal pregnancy without
      signs of active bleeding, who were randomly assigned to undergo either systemic
      methotrexate therapy or laparoscopic salpingostomy. INTERVENTION(S): Standard
      health-related quality of life questionnaires administered before and 2 days, 2
      weeks, 4 weeks. and 16 weeks after confirmative laparoscopy. MAIN OUTCOME
      MEASURE(S): Health-related quality of life. RESULT(S): Health-related quality of
      life was impaired most severely 2 days after confirmative laparoscopy in both
      treatment groups and improved during follow-up. Health-related quality of life
      was impaired more severely after systemic methotrexate therapy than after
      laparoscopic salpingostomy. Medically treated patients had more limitations in
      physical functioning, role functioning, and social functioning; had worse health
      perceptions, less energy, more pain, more physical symptoms, and a worse overall
      quality of life; and were more depressed than surgically treated patients.
      CONCLUSION(S): Systemic methotrexate therapy had a more negative impact on
      patients' health-related quality of life than did laparoscopic salpingostomy.
      This negative impact on patients' health-related quality of life of systemic
      methotrexate therapy should be taken into account when deciding on the
      appropriate therapy for tubal pregnancy.

PMID- 9757882
TI  - Systemic methotrexate therapy versus laparoscopic salpingostomy in tubal
      pregnancy. Part II. Patient preferences for systemic methotrexate.
AB  - OBJECTIVE: To investigate patient preferences for systemic methotrexate therapy
      relative to laparoscopic salpingostomy in the treatment of tubal pregnancy.
      DESIGN: Preference assessment in controlled clinical study. SETTING: Four
      hospitals and one infertility clinic. PATIENT(S): Forty patients who had been
      treated for tubal pregnancy and 40 nonpregnant controls. INTERVENTION(S):
      Preference for methotrexate therapy relative to salpingostomy was established
      during an interview. Two scenarios were offered for methotrexate therapy: one
      with and one without preceding diagnostic laparoscopy. Hypothetical tubal patency
      rates after methotrexate therapy were varied in both scenarios until patients
      switched in their initial preference. MAIN OUTCOME MEASURE(S): Preference for
      systemic methotrexate therapy. RESULT(S): Only a few patients switched in their
      initial preference when the tubal patency rate after systemic methotrexate
      therapy was varied. Most preferred methotrexate therapy without an increase in
      the tubal patency rate in a scenario without preceding diagnostic laparoscopy. A
      small group never opted for methotrexate therapy even when it would guarantee a
      100% tubal patency rate. CONCLUSION(S): Systemic methotrexate therapy would be
      preferred by most patients as part of a completely nonsurgical management
      strategy. Tubal patency was a decisive factor for treatment preference in a
      minority of patients only.

PMID- 9757883
TI  - Transvaginal salpingoscopy: an office procedure for infertility investigation.
AB  - OBJECTIVE: To evaluate the feasibility of salpingoscopy as an office procedure
      using transvaginal access to the pelvic cavity. DESIGN: Descriptive study.
      SETTING: Gynecology office. PATIENT(S): Infertile women with no obvious pelvic
      pathology. INTERVENTION(S): Transvaginal Veress needle puncture and peritoneal
      distension by saline. MAIN OUTCOME MEASUREMENT(S): Visualization of distal tubal
      segment. cannulation, and salpingoscopy. RESULT(S): The fimbriae were visualized
      in all patients. Cannulation of the distal tubal segment was achieved without
      manipulation of the tube in 20% before ovulation and 55% in the early luteal
      phase. CONCLUSION(S): Transvaginal fimbrioscopy and salpingoscopy can be
      performed as an office procedure in patients without obvious pelvic pathology. In
      combination with hydrolaparoscopy and dye hydrotubation, the technique provides
      comprehensive screening of the tuboovarian structures in the early stage of
      infertility investigation.

PMID- 9757884
TI  - Results of laparoscopic treatments of ovarian endometriomas: laparoscopic ovarian
      fenestration and coagulation.
AB  - OBJECTIVE: To determine the long-term results of laparoscopic fenestration and
      coagulation of ovarian endometriomas and to compare them with the results of
      ovarian cystectomy performed by either laparotomy or laparoscopy. DESIGN: Case
      control study. SETTING: Two university-affiliated hospitals. PATIENT(S): One
      hundred fifty-six premenopausal women with ovarian endometriomas of at least 3 cm
      in diameter (stage 3 and 4 endometriosis, revised American Fertility Society
      classification). INTERVENTION(S): Laparoscopic ovarian fenestration and
      coagulation (group 1, 80 patients); laparoscopic ovarian cystectomy (group 2, 23
      patients); and ovarian cystectomy by laparotomy and microsurgical technique
      (group 3, 53 patients). MAIN OUTCOME MEASURE(S): Operative findings, recurrence
      rate, and cumulative clinical pregnancy rate (PR) over a 36-month follow-up
      period. RESULT(S): The mean (+/-SD) time to first pregnancy was significantly
      shorter in group 1 (1.4+/-0.2 years) than in group 2 (2.2+/-0.5 years) or group 3
      (2.4+/-0.5 years). The difference between the cumulative clinical PR between the
      three groups was not statistically significant after 36 months of follow-up. The
      difference in the recurrence rate among groups 1, 2, and 3 was not statistically
      significant. CONCLUSION(S): Laparoscopic ovarian fenestration and coagulation of
      endometriomas leads to faster conception than ovarian cystectomy by laparotomy.
      Laparoscopic ovarian fenestration and coagulation of endometriomas is associated
      with cumulative clinical PRs and recurrence rates over 36 months that are similar
      to those associated with ovarian cystectomy.

PMID- 9757885
TI  - Robotically assisted laparoscopic microsurgical uterine horn anastomosis.
AB  - OBJECTIVE: To evaluate the feasibility, safety, and sterility issues with regard
      to the use of a robotic device to perform uterine horn anastomosis in a live
      porcine model. DESIGN: Prospective animal study. SETTING: Landrace-Yorkshire pigs
      in a conventional laboratory setting. INTERVENTION(S): Six female pigs underwent
      laparoscopic bipolar electrocoagulation of the distal uterine horns. Two weeks
      later, the uterine horns were reanastomosed laparoscopically with use of a
      robotic system for microsuturing. Necropsy was performed 4 weeks later to assess
      postoperative adhesions and anastomosis patency. MAIN OUTCOME MEASURE(S): Tubal
      patency; secondary measures were operative time, complications, and surgeon
      fatigue. RESULT(S): The mean (+/-SD) total operative time per animal was 170+/-34
      minutes including setting up and dismantling the robotic arms. The robot
      functioned well with only minor technical problems. All pigs survived both
      surgeries with no perioperative complications related to the use of the robot.
      Patency was confirmed after completing each anastomosis (12 anastomoses; 100%
      patency). Four weeks later, necropsy showed that eight anastomoses were still
      patent (67%). Only one pig had bilateral occlusion. Surgeon's fatigue was mild
      for each animal study. CONCLUSION(S): Robotic technology can be used safely in
      creating laparoscopic microsurgical anastomoses. The robot functioned properly in
      a sterile operating room environment. Adequate patency rates were achieved during
      the acute phase and at 4-week follow-up. Robotic technology has the potential to
      make laparoscopic microsuturing easier.

PMID- 9757886
TI  - Growth factor regulation of insulin-like growth factor binding protein secretion
      by cultured human granulosa-luteal cells.
AB  - OBJECTIVE: To examine the effects of epidermal growth factor (EGF), transforming
      growth factor-beta (TGF-beta), and fibroblast growth factor (FGF) on insulin-like
      growth factor binding protein (IGFBP) secretion by cultured human granulosa
      luteal cells. DESIGN: Granulosa-luteal cells obtained at the time of oocyte
      harvest for IVF were cultured in serum-free medium in the presence or absence of
      EGF, TGF-beta, or FGF. Conditioned medium then was analyzed by Western ligand
      blot and immunoradiometric assays. SETTING: An academic medical center.
      PATIENT(S): Women undergoing IVF. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      IGFBP-1 secretion. RESULT(S): By Western ligand blot analysis, IGFBP-1 levels
      were 1.4-fold to 7.4-fold higher in conditioned medium from cells cultured in the
      presence of EGF than in control medium. By immunoradiometric assay, IGFBP-1
      levels increased from 1.6 to 9.9 times over control. The TGF-beta had no apparent
      effect, and FGF did not consistently stimulate IGFBP-1 secretion. CONCLUSION(S):
      The EGF may decrease intrafollicular bioavailable IGF levels by increasing
      inhibitory IGFBPs, thereby leading to arrest of follicular development.
      Interactions between the EGF and IGF systems may be involved in the processes
      governing human ovarian follicle maturation and atresia.

PMID- 9757887
TI  - Oxytocin enhances the prolactin response to vasoactive intestinal polypeptide in
      healthy women.
AB  - OBJECTIVE: To establish whether oxytocin modifies the stimulatory effect of
      vasoactive intestinal polypeptide (VIP) on prolactin secretion in healthy women.
      DESIGN: Controlled clinical study. SETTING: Healthy women in an academic research
      environment. PATIENT(S): Seven healthy women (aged 24-32 years) were tested on
      the 22nd day of two consecutive normal menstrual cycles. INTERVENTION(S):
      Vasoactive intestinal polypeptide (4 pmol x kg(-1) x min(-1) in 50 mL of normal
      saline infused i.v. for 60 minutes) was administered in either the presence or
      absence of concurrent treatment with oxytocin (2 IU injected plus 0.07 IU/min
      infused for 60 minutes). MAIN OUTCOME MEASURE(S): Serum prolactin levels.
      RESULT(S): The administration of VIP induced a significant increase in serum
      prolactin levels, with a mean peak response 1.6 times higher than baseline at 45
      minutes after injection. In the presence of oxytocin, the prolactin response to
      VIP was significantly higher, with a mean peak response 2 times higher than
      baseline. CONCLUSION(S): These data suggest that in healthy women, oxytocin
      facilitates the regulation of the stimulating effect of VIP on prolactin
      secretion.

PMID- 9757888
TI  - Follicle-stimulating hormone measured in unextracted urine: a reliable tool for
      easy assessment of ovarian capacity.
AB  - OBJECTIVE: To determine the presence of FSH in unextracted urine of
      perimenopausal women using a microparticle enzyme immunoassay kit on an AxSYM
      random access immunoassay analyzer. DESIGN: Controlled descriptive study.
      SETTING: A large teaching hospital and infertility clinic. PATIENT(S): Forty
      perimenopausal women aged 32-55 years admitted to our clinic for a gynecological
      operation. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Mean serum FSH level
      and urinary FSH in early-morning urine, in a random void urine sample, and in 24
      hour urine on the same day. FSH in urine on the day of excretion and 1 and 4
      weeks thereafter, stored under various conditions. FSH in urine before and after
      extraction. RESULT(S): The Pearson's correlation coefficient between mean serum
      FSH levels and urinary FSH in early morning urine was 0.904, in a random void
      0.915, and in 24-hour urine 0.857. Determination of optimal storage conditions
      revealed that urine was best kept at 4 degrees C without any additive. The
      correlation between FSH in extracted and unextracted urine was 98.9%.
      CONCLUSION(S): In perimenopausal women, FSH can be reliably measured in
      unextracted urine. The correlation between urinary FSH and a random void urine
      sample and mean FSH from a serial serum sample is very high. Urine can be stored
      for 4 weeks at 4 degrees C without loss of FSH immunoreactivity.

PMID- 9757889
TI  - Expression of the apoptosis-related genes, caspase-1, caspase-3, DNA
      fragmentation factor, and apoptotic protease activating factor-1, in human
      granulosa cells.
AB  - OBJECTIVE: To investigate protein and messenger RNA expression products for a
      subset of apoptosis-related genes in human granulosa cells. DESIGN: In vitro
      experiment. SETTING: Department of Obstetrics, Gynecology, and Reproductive
      Biology, Brigham and Women's Hospital, Harvard Medical School, Boston,
      Massachusetts. PATIENT(S): Women undergoing oocyte retrieval for IVF after
      ovulation induction with gonadotropins. INTERVENTION(S): Granulosa cells were
      isolated from follicular aspirates after oocyte removal. MAIN OUTCOME MEASURE(S):
      Reverse transcription polymerase chain reaction and Western blotting for
      apoptosis-related gene products. RESULT(S): The expression of caspase-1, caspase
      3, DNA fragmentation factor, and apoptotic protease activating factor-1, which
      are intermediate molecules in phylogenetically conserved apoptotic pathways, was
      demonstrated in granulosa cells from patients undergoing IVF. Moreover, proforms,
      but not activated enzymes, for both caspase-1 and caspase-3 were observed.
      CONCLUSION(S): Granulosa cells from patients undergoing IVF have intrinsic
      apoptotic machinery that could be activated for tissue remodeling.

PMID- 9757890
TI  - Interleukin-1beta and interleukin-1alpha may affect the implantation rate of
      patients undergoing in vitro fertilization-embryo transfer.
AB  - OBJECTIVE: To investigate whether interleukin-1beta (IL-1beta) and interleukin
      1alpha (IL-1alpha) affect the implantation rate of patients undergoing IVF-ET.
      DESIGN: Follicular fluid and serum were obtained on the day of hCG
      administration, the day of oocyte retrieval, and the day of embryo transfer.
      SETTING: Cellular immunology laboratory in a research institute, a high
      technology IVF unit in a medical center, and a university hospital. PATIENT(S):
      Thirty-three women who were undergoing IVF-ET. MAIN OUTCOME MEASURE(S): IL-1beta
      and IL-1alpha were measured by specific ELISA and their levels were correlated
      with the implantation rate. RESULT(S): Classification of IVF-ET patients
      according to their implantation rate revealed significantly higher amounts of
      follicular fluid IL-1beta in the implantation versus nonimplantation cycles
      (68.5+/-24.6 pg/mL versus 20.5+/-13.4 pg/mL); The difference between the level of
      IL-1alpha in the two groups was not statistically significant(11.6+/-5.1 pg/mL
      versus 7.3+/-1.9 pg/mL). In parallel, systemic FSH/hMG-dependent IL-1beta and IL
      1alpha production was observed in implantation cycles but not in nonimplantation
      cycles. Statistically significant IL-1beta and IL-1alpha production was observed
      after administration of hCG. CONCLUSION(S): Gonadotropins used during IVF-ET
      induce local and systemic production of IL-1beta and IL-1alpha. In addition, the
      implantation rate for IVF-ET patients who have detectable serum concentrations of
      IL-1beta and IL-1beta on the day of hCG administration could be higher than the
      rate for IVF-ET patients who do not have detectable concentrations of these
      cytokines.

PMID- 9757891
TI  - Changes in vascular endothelial growth factor levels and the risk of ovarian
      hyperstimulation syndrome in women enrolled in an in vitro fertilization program.
AB  - OBJECTIVE: To evaluate plasma and follicular fluid levels of vascular endothelial
      growth factor (VEGF) in women undergoing controlled ovarian hyperstimulation to
      establish the possible role of this growth factor as a predictive marker of
      ovarian hyperstimulation syndrome (OHSS). DESIGN: Prospective observational
      study. SETTING: University hospital infertility unit. PATIENT(S): Fifteen women
      at risk of OHSS and 15 controls. INTERVENTION(S): An IM injection of hCG was
      administered; plasma and follicular fluid samples were collected 34-38 hours
      after administration of hCG. MAIN OUTCOME MEASURE(S): VEGF levels in plasma and
      in follicular fluid. RESULT(S): VEGF levels increased after hCG administration in
      the patients at risk of developing OHSS and in those who developed OHSS. Further,
      on the day of the oocyte retrieval the increase in the VEGF levels in the plasma
      of the patients who developed OHSS was statistically significant compared with
      the increase in the levels in the women who did not. On the same day, the levels
      of VEGF in follicular fluid were 10 times greater than those in plasma.
      CONCLUSION(S): Plasma levels of VEGF peak after hCG administration and are
      related to the risk of developing OHSS.

PMID- 9757892
TI  - No evidence of the inactivating mutation (C566T) in the follicle-stimulating
      hormone receptor gene in Brazilian women with premature ovarian failure.
AB  - OBJECTIVE: To investigate the presence of FSH receptor gene mutations in women
      with premature ovarian failure (POF). DESIGN: Clinical and molecular studies.
      SETTING: Research laboratory in a university setting. PATIENT(S): Fifteen 46,XX
      women with POF and 42 normal fertile controls. INTERVENTION(S): Exon 7 was
      amplified and digested with BsmI to screen for the previously described
      inactivating mutation C566T. Exon 10 was screened for mutations by denaturing
      gradient gel electrophoresis and direct sequencing. MAIN OUTCOME MEASURE(S):
      Polymerase chain reaction followed by restriction enzyme analysis, denaturing
      gradient gel electrophoresis, and direct sequencing. RESULT(S): No inactivating
      mutations were identified in exons 7 and 10 of the FSH receptor gene in women
      with familial or sporadic POF. Exon 10 had two polymorphisms, G919A and G2039A,
      whose allelic frequencies were 46.7% and 56.6%, respectively, in women with POF.
      The allelic frequency of both polymorphisms was 59.5% in normal fertile controls.
      CONCLUSION(S): No inactivating mutations in exons 7 and 10 of the FSH receptor
      gene were identified in Brazilian women with POF. A high frequency of two
      polymorphisms that are in linkage disequilibrium was found in exon 10 of this
      gene.

PMID- 9757893
TI  - Lateral cervical displacement is associated with endometriosis.
AB  - OBJECTIVE: To report on a series of cases of lateral cervical displacement and
      uterosacral ligament scarring associated with endometriosis. DESIGN: Case series.
      SETTING: Academic medical center. PATIENT(S): Three nulliparous women with
      chronic pelvic pain, lateral cervical displacement, and uterosacral nodularity.
      INTERVENTION(S): Physical examination to evaluate for lateral cervical
      displacement. Laparoscopic surgery to evaluate for endometriosis and uterosacral
      ligament involvement. MAIN OUTCOME MEASURE(S): Displacement of the entire cervix
      lateral to the midline of the vagina. Presence of endometriosis on the affected
      uterosacral ligament. RESULT(S): All three patients had lateral cervical
      displacement and implants of endometriosis and scarring on the uterosacral
      ligament ipsilateral to the displaced cervix. CONCLUSION(S): In women with pelvic
      pain, lateral cervical displacement due to uterosacral scarring may be a physical
      finding associated with endometriosis.

PMID- 9757894
TI  - Stenosis of the external cervical os: an association with endometriosis in women
      with chronic pelvic pain.
AB  - OBJECTIVE: To report a simple technique for diagnosing stenosis of the external
      cervical os and to evaluate an association between stenosis of the external
      cervical os and endometriosis in women with chronic pelvic pain. DESIGN: Case
      series. SETTING: Academic medical center. PATIENT(S): Twenty-five women with
      chronic pelvic pain and stenosis of the external cervical os. INTERVENTION(S):
      Measurement of the diameter of the external cervical os. MAIN OUTCOME MEASURE(S):
      Association between cervical stenosis and surgically documented endometriosis in
      women with chronic pelvic pain. RESULT(S): Endometriosis was visually documented
      at surgery for 24 of 25 women with chronic pelvic pain and stenosis of the
      external cervical os. CONCLUSION(S): Endometriosis is a common finding in women
      with both stenosis of the external cervical os and chronic pelvic pain.

PMID- 9757895
TI  - A randomized comparison of the methods of sperm preparation for intrauterine
      insemination.
AB  - OBJECTIVE: To compare the effectiveness of three methods of sperm preparation for
      IUI during superovulation of infertile women. DESIGN: Randomized assignment of
      one of three sperm preparation methods. SETTING: University infertility practice.
      PATIENT(S): Infertile couples undergoing superovulation and IUI. INTERVENTION(S):
      The method of preparation of sperm for IUI during superovulation was assigned
      randomly to double centrifugation, multiple-tube swim-up, or Percoll density
      gradient. MAIN OUTCOME MEASURE(S): Total number and percent recovery of motile
      sperm, percent of recovered sperm with normal morphology, and cycle fecundity.
      RESULT(S): No method of sperm preparation provided better cycle fecundity than
      the others despite differences in sperm recovery. CONCLUSION(S): Double
      centrifugation, multiple-tube swim-up, and Percoll density gradient sperm
      preparation for IUI yield similar cycle fecundity rates.

PMID- 9757896
TI  - Spermatozoa with chromosomal abnormalities may result in a higher rate of
      recurrent abortion.
AB  - OBJECTIVE: To determine whether sperm aneuploidy can lead to abortion. DESIGN:
      Clinical study. SETTING: Couples with reproductive problems evaluated in a
      private diagnostic laboratory. PATIENT(S): Two men whose wives had histories of
      multiple abortions. INTERVENTION(S): Whole and Percoll-processed semen samples
      were analyzed. MAIN OUTCOME MEASURE(S): The results of fluorescence in situ
      hybridization. RESULT(S): Aneuploidy rates in Percoll-processed samples were
      higher than those found in whole specimens. Aneuploid spermatozoa also displayed
      greater motility. CONCLUSION(S): Sperm aneuploidy should be studied before and
      after Percoll capacitation in all couples with unexplained infertility.

PMID- 9757897
TI  - Birth after cryopreservation of immature oocytes with subsequent in vitro
      maturation.
AB  - OBJECTIVE: To establish the clinical feasibility of using cryostored germinal
      vesicle oocytes for IVF and ET. DESIGN: Case report. SETTING: Private infertility
      clinic. PATIENT(S): A 28-year-old woman with tubal infertility undergoing IVF
      therapy. INTERVENTION(S): Oocytes collected after ovarian stimulation were frozen
      without insemination or were inseminated, fertilized, and frozen as cleavage
      stage embryos. No fresh oocyte or embryo transfer was undertaken. All oocytes
      were thawed, and those that survived were used for IVF-ET. MAIN OUTCOME
      MEASURE(S): Oocyte cryosurvival, in vitro maturation, fertilization, embryo
      development, and pregnancy outcome. RESULT(S): None of 16 mature oocytes survived
      thawing; however, three of 13 germinal vesicle oocytes survived. After 30 hours
      in vitro maturation two oocytes had matured and underwent intracytoplasmic sperm
      injection with the partner's sperm. Both fertilized normally and were transferred
      to the patient. The woman delivered an apparently healthy female infant at 40
      weeks. CONCLUSION(S): This case report proves the feasibility if not the
      efficiency of using immature oocytes for cryostorage, coupling both
      cryopreservation and in vitro maturation.

PMID- 9757898
TI  - Does pelvic magnetic resonance imaging differentiate among the histologic
      subtypes of uterine leiomyomata?
AB  - OBJECTIVE: To evaluate if pelvic magnetic resonance imaging (MRI) is reliable for
      differentiating leiomyoma subtypes. DESIGN: Prospective study. SETTING: Academic
      center. PATIENT(S): Forty-five patients underwent MRI before surgery for
      leiomyomata. INTERVENTION(S): One radiologist blinded to patient history and
      histologic diagnosis recorded the MRI characteristics and classification of the
      largest leiomyoma. MAIN OUTCOME MEASURE(S): Comparison of MRI and histologic
      diagnoses. RESULT(S): Leiomyoma subtypes were diagnosed accurately by MRI in 69%
      of cases. Magnetic resonance imaging had a 95% sensitivity and 72% specificity
      for diagnosing an uncomplicated leiomyoma and a 10% sensitivity and 100%
      specificity for a cellular leiomyoma. For cystic leiomyomata, the sensitivity was
      80% and specificity was 98%, and for hemorrhagic leiomyomata, 100% and 86%,
      respectively. Magnetic resonance imaging correctly diagnosed all malignant tumors
      and did not incorrectly diagnose a leiomyoma as a leiomyosarcoma in any case. Ill
      defined MRI margins were significantly more likely to be leiomyosarcoma, whereas
      well-defined margins were characteristic of benign lesions. Hemorrhagic
      leiomyomata were significantly more likely to be hyperintense on T1-weighted
      images than other subtypes. CONCLUSION(S): Although MRI is only fairly accurate
      in differentiating the subtypes of benign uterine smooth muscle tumors, signal
      intensities and margin characteristics are useful to distinguish accurately
      benign from malignant tumors.

PMID- 9757900
TI  - Pelvic endometriosis--the same or different entities in disguise?

PMID- 9757899
TI  - Pelvic endometriosis--the same or different entities in disguise?

PMID- 9757901
TI  - Pelvic endometriosis--the same or different entities in disguise?

PMID- 9757902
TI  - Pelvic endometriosis--the same or different entities in disguise?

PMID- 9757903
TI  - Benediction for diagnostic laparoscopy in pelvic pain syndromes and neurotic
      genes?

PMID- 9757904
TI  - Role of transvaginal ultrasonography in the diagnosis of ectopic pregnancy.

PMID- 9757905
TI  - Success rates of methotrexate in ectopic pregnancy?

PMID- 9757906
TI  - Success rates of methotrexate in ectopic pregnancy?

PMID- 9757907
TI  - The Book of Samuel, mice, leptin, pheromones, and anorexia nervosa.

PMID- 9757908
TI  - A negative study with power?

PMID- 9757909
TI  - Immunoregulation by CD4 T cells in the induction of specific immunological
      unresponsiveness to alloantigens in vivo: evidence for a reduction in the
      frequency of alloantigen-specific cytotoxic T cells in vitro.
AB  - Donor-specific unresponsiveness to allogeneic cardiac allografts in mice can be
      induced by the combined pretreatment with donor alloantigen and anti-CD4 antibody
      (anti-CD4+DST). We have investigated whether the induction of unresponsiveness in
      this model is due to the presence of T cells that regulate immune responsiveness
      towards the allograft. First, we analysed the functional characteristics of
      splenocytes from pretreated mice at the time of transplantation. A significant
      reduction in the frequency of donor specific cytotoxic precursor was found only
      after the anti-CD4+DST treatment. Next, we designed an in vitro assay to identify
      the phenotype of the splenocyte population responsible. CD4+ and CD4- fractions
      were purified from mice treated with anti-CD4+DST or anti-CD4 alone (controls) by
      cell sorting. Interestingly, only the addition of CD4+ cells from anti-CD4+DST
      treated mice resulted in a selective reduction and a bimodal distribution in the
      donor specific CTLp response, indicating the presence of a regulatory population.
      CD4+ cells from controls did not have this effect. These in vitro findings were
      substantiated by adoptive transfer experiments in vivo. These data demonstrate
      that CD4+ cells with the ability to regulate immune responsiveness to a cardiac
      allograft are present at the time of transplantation following pretreatment with
      donor alloantigen in combination with anti-CD4.

PMID- 9757910
TI  - The presentation of self and allogeneic MHC peptides to T lymphocytes.
AB  - The presentation of donor-derived MHC peptides by recipient APCs to T cells is an
      essential component of the rejection of allografts (indirect allorecognition).
      Initial alloreactive T cell response is confined to a few well processed and
      presented dominant determinants on donor MHC. However, during long-term graft
      rejection, T cell response spreads to formerly poorly presented cryptic
      allogeneic MHC peptides. This phenomenon is likely to play an important role in
      the amplification and the perpetuation of the rejection process. Additionally, we
      present evidence that T cell repertoire selection to allogeneic MHC peptides is
      acquired via recognition of self-MHC peptides presented in the thymus during
      ontogeny. Supporting this view, we have shown that indirect alloresponses can
      lead to self-T cell tolerance breakdown to cross-reactive determinants on self
      MHC molecules or alternatively that sensitization of recipients to self-MHC
      peptides can lead to accelerated graft rejection. It is therefore essential to
      determine the factors which govern the processing and presentation of self and
      allogeneic MHC molecules and to elucidate the mechanisms regulating subsequent T
      cell responses in order to design antigen-specific based immune therapies in
      transplantation.

PMID- 9757911
TI  - Characterization of self-glutamic acid decarboxylase 65-reactive CD4+ T-cell
      clones established from Japanese patients with insulin-dependent diabetes
      mellitus.
AB  - To investigate autoimmunity to glutamic acid decarboxylase (GAD) 65 in Japanese
      patients with insulin-dependent diabetes mellitus (IDDM, type I diabetes), we
      established seven CD4+ T-cell clones, by stimulating peripheral blood mononuclear
      cells (PBMC) of six IDDM patients, using a mixture of overlapping human GAD65
      peptides. No GAD65 autoreactive T-cell clones were evidenced in four healthy
      controls. Specificities of T-cell clones were as follows: (a) two clones specific
      to GAD65 p111-131 (residue 111 to 131) + DR53 (DRB4*0103); (b) one clone specific
      to GAD65 p413-433 + DR1 (DRB1*0101); (c) two clones specific to GAD65 p200-217 +
      either DR9 (DRB1*0901) or DR8 (DRB1*0802); and (d) two clones specific to GAD65
      p368-388 + DP2 (DPA1*01 or 0201-DPB1*0201). Two DR53-restricted and one DR1
      restricted T-cell clones, responded to a recombinant human GAD65 protein, and
      showed cytotoxicity against B lymphoblastoid cell lines pre-pulsed with the
      peptides. Six T-cell clones exhibited the Th1-like phenotype. Interestingly, two
      DR53-restricted T-cell clones killed a Fas-deficient B lymphoblastoid cell line,
      thereby indicating that cytotoxicity was not completely dependent on a Fas-Fas
      ligand interaction. Thus, the T-cell epitopes were mapped in a limited portion of
      GAD65 protein, with a tendency to be restricted by disease-associated HLA-DR, but
      not DQ molecules.

PMID- 9757912
TI  - Multiple epitopes of HLA-DRB1*0411 are recognized by T-cell clones originated
      from individuals carrying other DR4 subtypes.
AB  - HLA polymorphism dictates the binding and recognition of specific peptides,
      leading to variations in individual immune responses and may contribute to
      autoimmune disorders and outcome in organ transplantation. We have studied the
      molecular basis for the cellular recognition of DRB1*0411 in individuals carrying
      other sequence-related DR4-alleles by characterization of T-cell clones (TLC). A
      set of 166 TLC were raised by priming cells from DRB1*0401,0402 and
      DRB1*0405,0901 individuals and 52 of them recognized DRB1*0411. Five distinct
      patterns of T-cell allorecognition were found: DRB1*0411 alone, DRB1*0411 and
      0405, DRB1*0411 and 0406, DRB1*0411 and 0407 and DRB1*0411, 0406 and 0407,
      depending on responder phenotypes and epitopes recognized by their T cells. A
      stretch of 30 amino acids on DRB1*0411 from positions 57 to 86 behaves as a
      functional domain and residues S57, R71, E74 and V86 seem to be crucial in
      forming immunogenic determinants recognized by these TLC. The knowledge of shared
      amino acid residues between closely related DR4 alleles, which show similar
      patterns of recognition by T cells could also be useful in the selection of
      prospective donors for clinical transplantation of solid organs or bone marrow.

PMID- 9757913
TI  - Tumor necrosis factor locus: genetic organisation and biological implications.
AB  - TNF genes determine strength, effectiveness, and duration of local and systemic
      inflammatory reactions, as well as repair and recovery from infectious and toxic
      agents. Multiple pro- and anti-inflammatory activities of TNF factors are
      conditioned by their profound effects on metabolism of many cell types, their
      activation state, cell survival and others. TNF genes show strong linkage
      disequilibrium with HLA class I and class II genes and with other genes in the
      MHC region relevant to immuneregulation. Structural or regulatory defects in TNF
      genes may contribute to pathogenesis of MHC associated diseases especially those
      with inflammatory and autoimmune components.

PMID- 9757914
TI  - HLA-DR and -DQ associations with melioidosis.
AB  - Melioidosis is an important infectious disease of southeast Asia caused by an
      intracellular bacterium, Burkholderia pseudomallei. Cellular immunity is
      postulated to play important roles in immunity to melioidosis that may influence
      the severity and clinical outcome of the disease. The present study was
      undertaken to investigate possible associations of melioidosis with HLA class II
      alleles. HLA typing of HLA-DRB1, -DQA1, and -DQB1 was performed using polymerase
      chain reaction and sequence-specific oligonucleotide hybridization (PCR-SSO).
      Seventy-nine melioidosis patients and 105 healthy, ethnically and geographically
      matched controls were studied. Among 24 DRB1 alleles, 7 DQA1 alleles, and 13 DQB1
      alleles identified in this population, an association with melioidosis was
      observed with DRB1*1602 which was increased in melioidosis patients (10.1%)
      compared to normal controls (4.8%), p = 0.047 (odds ratio (OR) = 2.25). In
      addition, significant increase of DRB1*1602 allele frequency and decrease of
      DQA1*03 were also observed in septicemic melioidosis patients, the most severe
      form of the disease (p = 0.01, OR = 3.10; and p = 0.047, respectively).
      Furthermore, a trend of association of DRB1*0701, DQA1*0201, and DQB1*0201 with
      relapse cases of melioidosis was also noted. In contrast, no HLA association was
      observed in localized melioidosis or melioidosis with diabetes mellitus. These
      findings provide the suggestive evidence of an immunogenetic basis of certain
      aspects of melioidosis.

PMID- 9757915
TI  - Assignment of HLA-antigens in CREGs facilitates the detection of acceptable
      mismatches in highly sensitized patients.
AB  - The purpose of this study was to investigate whether in highly sensitized
      patients (HSPs) the acceptable HLA-A and -B mismatches (AMs) can be predicted on
      the basis of patients' HLA-phenotype. To this affect, 1000 historical serum
      samples obtained from 50 HSPs (PRA > 60%), panel reactive antibodies (PRA) value
      and the specificity of class I anti-HLA-antibodies were detected by two
      techniques in parallel: An anti-human globulin augmented cytotoxicity (AHG-CDC)
      and an Elisa technique. Thereafter, class I HLA-antigens of the nonreactive cells
      in the screening panel and class I HLA-antigens of the patients were assigned to
      CREGs. The AMs for each one of the patients were detected using a separate cell
      panel, which was prepared in a way to include almost all the HLA-antigens
      belonging to the CREGs of the patients as well as to those of the nonreactive
      cells in the screening panel. It was found that the AMs in HSPs, detected with
      this protocol were more, compared to those we usually detect using only the HLA
      antigens of the nonreactive cells in the screening panel (up to 8 versus 2-5).
      Both, the definitively detected AMs, and the HLA-specificities of the nonreactive
      cells of the screening panel belonged to the same CREGs. These CREGs were
      equivalent to the CREGs of class I HLA-phenotypes of each patient. The data
      presented in this paper introduce a new, rapid and easier way for the detection
      of AMs in HSPs. According to this proposed protocol, the assignment of patients'
      standard class I private HLA-phenotypes in CREGs, not only greatly facilitates
      the detection of AMs, but the detected AMs are also in fact significantly more
      than those determined by the conventional methodology. We have also confirmed
      that the majority of antibodies induced by HLA alloimmunization are directed
      against mismatched shared or public group epitopes CREGs. Moreover, we have
      confirmed that prospective matching for major CREGs would be feasible on a
      national level and would not significantly prolong waiting time, which could
      result in a significant augmentation of the potential donor pool.

PMID- 9757916
TI  - Saliva as DNA source for HLA typing.

PMID- 9757917
TI  - Gastric tonometry, tissue hypoxia and MSOF. Is there a link?

PMID- 9757920
TI  - Comparison of air tonometry with gastric tonometry using saline and other
      equilibrating fluids: an in vivo and in vitro study.
AB  - OBJECTIVE: 1) To compare saline gastric tonometry monitoring with air tonometry
      (Tonocap) in a group of general ICU patients. 2) An in vitro investigation of the
      performance of other fluids used in gastric tonometry and to assess the effects
      of variation of temperature and carbon dioxide concentration within the range
      encountered in clinical use. DESIGN: a) A prospective, observational study in ICU
      patients b) A comparative laboratory study. SETTING: The general Intensive Care
      Unit (ICU) and the laboratory at Leeds General Infirmary. PATIENTS AND
      PARTICIPANTS: Nine patients in the general ICU with severe sepsis or septic
      shock. MEASUREMENTS AND RESULTS: In vivo comparison of saline and air tonometry
      demonstrated a difference between the two techniques. Bland & Altman analysis
      showed a mean bias in the measurement of gastric PCO2 of 1.88 kPa with a
      precision of 1.22 kPa, with saline giving the lower result. In vitro, saline, air
      (Tonocap), gelatin and heparinised blood were used, at temperatures of 33-42
      degrees C and at carbon dioxide concentrations of 4-8 kPa. While gelatin and
      blood gave unpredictable results, dependent on temperature and carbon dioxide
      concentration, air tonometry gave highly reproducible results. A consistent bias
      between the results with saline and air tonometry was seen over the range of
      temperatures and carbon dioxide (CO2) concentrations studied. The mean bias was
      0.85 kPa with a precision of 0.40 kPa, saline consistently giving lower results.
      CONCLUSIONS: There are clinically significant differences in values for gastric
      mucosal PCO2 measured by air tonometry and saline tonometry both in vivo and in
      vitro.

PMID- 9757919
TI  - Gastric intramucosal pH-guided therapy in patients after elective repair of
      infrarenal abdominal aneurysms: is it beneficial?
AB  - OBJECTIVE: To determine if gastric intramucosal pH (pHi)-guided therapy reduces
      the number of complications and length of stay in the intensive care unit (ICU)
      or the hospital after elective repair of infrarenal abdominal aortic aneurysms.
      DESIGN: Prospective, randomized study. SETTING: Surgical intensive care unit
      (SICU) of a University Hospital. PATIENTS: Fifty-five consecutive patients
      randomized to group 1 (pHi-guided therapy) or to group 2 (control).
      INTERVENTIONS: Patients of group 1 with a pHi of lower than 7.32 were treated by
      means of a prospective protocol in order to increase their pHi to 7.32 or more.
      MEASUREMENTS AND RESULTS: pHi was determined in both groups on admission to the
      SICU and thereafter at 6-h intervals. In group 2, the treating physicians were
      blinded for the pHi values. Complications, APACHE II scores, duration of
      endotracheal intubation, fluid and vasoactive drug treatment, treatment with
      vasoactive drugs, length of stay in the SICU and in the hospital and hospital
      mortality were recorded. There were no differences between groups in terms of the
      incidence of complications. We found no differences in APACHE II scores on
      admission, the duration of intubation, SICU or hospital stay, or hospital
      mortality. In the two groups the incidence of pHi values lower than 7.32 on
      admission to the SICU was comparable (41% and 42% in groups 1 and 2,
      respectively). Patients with pHi lower than 7.32 had more major complications
      during SICU stay (p < 0.05), and periods more than 10 h of persistently low pHi
      values (< 7.32) were associated with a higher incidence of SICU complications (p
      < 0.01). CONCLUSIONS: Low pHi values (< 7.32) and their persistence are
      predictors of major complications. Treatment to elevate low pHi values does not
      improve postoperative outcome. Based on these data, we cannot recommend the
      routine use of gastric tonometers for pHi-guided therapy in these patients.
      Further studies are warranted to determine adequate treatment of low pHi values
      that results in beneficial effects on the patient's postoperative course and
      outcome.

PMID- 9757918
TI  - Applications of thrombolytic therapy.

PMID- 9757921
TI  - Physiologic evaluation of non-invasive pressure support ventilation in trauma
      patients with acute respiratory failure.
AB  - OBJECTIVE: To investigate the effectiveness of noninvasive (face mask) versus
      invasive (endotracheal tube) equal pressure values on blood gases and respiratory
      pattern and to evaluate the feasibility of using mask ventilation after the short
      term physiologic study. DESIGN: Open, prospective, physiologic study and
      uncontrolled clinical study. SETTING: Intensive care unit of a trauma center.
      PATIENTS: 22 intubated trauma patients were studied. INTERVENTIONS: Patients were
      intubated and ventilated in a pressure support mode (IPSV) of 13.5 +/- 1.5 cmH2O
      and a post end-expiratory pressure (PEEP) of 5.8 +/- 2.57 cmH2O. After a T-piece
      trial to assess patient's ability to breath spontaneously, patients were switched
      over to noninvasive pressure support (NIPSV). The pressure levels were set as
      during IPSV. Blood gases and respiratory parameters were measured during IPSV,
      during the T-piece trial, and after 1 h of NIPSV. After the physiologic study,
      all patients were asked if they wished to continue on NIPSV. The patient's
      subjective compliance with IPSV and NIPSV was measured by means of an arbitrary
      score. A successful outcome was defined as no need for reintubation. MEASUREMENTS
      AND RESULTS: IPSVand NIPSV showed no statistical differences for blood gas and
      respiratory parameters by using the same values of PSV (13 +/- 5 vs 12.8 +/- 1.7
      cmH2O, NS) and PEEP (5.8 +/- 2.5 and 5.2 +/- 2.2 cmH2O NS). The median length of
      time on NIPSV was 47 h (range 6 to 144). All patients wished to continue on
      NIPSV, but 9 patients (40.9%) were reintubated after 54 +/- 54 h. Six of them
      died after 36 +/- 13 days while still on mechanical ventilation. There was no
      statistically significant difference in compliance score between IPSVand NIPSV.
      CONCLUSIONS: NIPSV is comparable to IPSV in terms of blood gases and respiratory
      pattern. The clinical uncontrolled study indicates that NIPSV could be used in
      selected trauma patients.

PMID- 9757922
TI  - An investigation into the effects of midazolam and propofol on human respiratory
      cilia beat frequency in vitro.
AB  - OBJECTIVE: Patients in intensive care are known to be prone to both upper and
      lower respiratory tract infection. Respiratory mucus forms a barrier to
      infection. Mucus transport rate (MTR) depends upon both the physical properties
      of mucus and the action of respiratory cilia. Patients undergoing anaesthesia are
      known to have a reduced MTR that may be related to a depressant effect on cilia
      beat frequency (CBF) by anaesthetic drugs. The aim of this study was to
      investigate the effects of two commonly used intensive care sedative agents,
      midazolam and propofol, on CBF using human nasal turbinate explants in vitro.
      DESIGN: We exposed ciliated tissue from human nasal turbinate explants to
      midazolam and propofol in supraclinical concentrations (20 microM midazolam and
      70 microM propofol) in a controlled and blinded manner for 90 min and measured
      CBF by the transmitted light technique. RESULTS: After 90 min, mean (SEM) CBF in
      the group exposed to midazolam and its control group were 13.0 (0.2) Hz and 12.9
      (0.3) Hz, respectively. Mean (SEM) CBF in the group exposed to propofol was 13.6
      (0.4) Hz and in the control group the value was 12.0 (0.6) Hz. There was no
      significant change in CBF (midazolam: p = 0.21, propofol: p = 0.31, MANOVA for
      repeated measures). CONCLUSIONS: We have found no effect of midazolam or propofol
      in supra-clinical concentrations upon CBF in human turbinate explants after a 90
      min exposure. This contrasts with previous work that has shown a depressant
      effect of inhalational anaesthetic agents on CBF.

PMID- 9757923
TI  - Effect of enteral versus parenteral feeding on hepatic blood flow and steady
      state propofol pharmacokinetics in ICU patients.
AB  - OBJECTIVE: The main objective of this study was to evaluate the effect of
      switching from parenteral to enteral feeding on liver blood flow and propofol
      steady-state blood concentrations in patients in the intensive care unit (ICU).
      DESIGN AND PATIENTS: Steady-state blood concentrations of propofol were measured
      in eight ICU patients before (on days D -3, D -2, and D -1) and after (on days D
      + 1, D + 2, and D + 3) switching from parenteral to enteral feeding (on day DO).
      All patients received a continuous intravenous infusion of propofol (4.5 mg x kg(
      1) x h(-1)) from several days before the start of the study, continuing
      throughout the experimental period. Hepatic blood flow was estimated by measuring
      steady-state D-sorbitol hepatic clearance. RESULTS: Hepatic blood flow was high
      and was not affected by switching from parenteral to enteral feeding: 33 +/- 8 ml
      x min(-1) x kg(-1) (mean +/- SD) and 33 +/- 10 ml min(-1) x kg(-1) on D -3 and D 
      1, respectively, as compared to 37 +/- 11 ml x min(-1) kg(-1) and 34 +/- 8 ml x
      min(-1) x kg(-1) on days D + 1 and D + 3, respectively. Systemic clearance of
      propofol was much higher than liver blood flow with average values on the six
      observation days ranging from 74.0 to 81.2 ml x min(-1) x kg(-1) and was not
      affected by switching from parenteral to enteral feeding. CONCLUSIONS: Liver
      blood flow and systemic clearance of propofol were not affected by switching from
      parenteral to enteral feeding in the eight ICU patients studied. Extrahepatic
      clearance accounted for at least two thirds of the overall systemic clearance of
      propofol.

PMID- 9757924
TI  - Patterns of neurophysiological abnormality in prolonged critical illness.
AB  - OBJECTIVE: To describe the various patterns of neurophysiological abnormalities
      which may complicate prolonged critical illness and identify possible
      aetiological factors. DESIGN: Prospective case series of neurophysiological
      studies, severity of illness scores, organ failures, drug therapy and hospital
      outcome. Some patients also had muscle biopsies. SETTING: General intensive care
      unit (ICU) in a University Hospital. PATIENTS: Forty-four patients requiring
      intensive care unit stay of more than 7 days. The median age was 60 (range 27-84
      years), APACHE II score 19 (range 8-33), organ failures 3 (range 1-6), and
      mortality was 23%. RESULTS: Seven patients had normal neurophysiology (group I),
      4 had a predominantly sensory axonal neuropathy (group II), 11 had motor
      syndromes characterised by markedly reduced compound muscle action potentials and
      sensory action potentials in the normal range (group III) and 19 had combinations
      of motor and sensory abnormalities (group IV). Three patients had abnormal
      studies but could not be classified into the above groups (group V). All patients
      had normal nerve conduction velocities. Electromyography revealed evidence of
      denervation in five patients in group III and five in group IV. There was no
      obvious relationship between the pattern of neurophysiological abnormality and
      the APACHE II score, organ failure score, the presence of sepsis or the
      administration of muscle relaxants and steroids. A wide range of histological
      abnormalities was seen in the 24 patients who had a muscle biopsy; there was no
      clear relationship between these changes and the neurophysiological
      abnormalities, although histologically normal muscle was only found in patients
      with normal neurophysiology. Only three of the eight patients from group III in
      whom muscle biopsy was performed had histological changes compatible with
      myopathy. CONCLUSIONS: Neurophysiological abnormalities complicating critical
      illness can be broadly divided into three types -- sensory abnormalities alone, a
      pure motor syndrome and a mixed motor and sensory disturbance. The motor syndrome
      could be explained by an abnormality in the most distal portion of the motor
      axon, at the neuromuscular junction or the motor end plate and, in some cases, by
      inexcitable muscle membranes or extreme loss of muscle bulk. The mixed motor and
      sensory disturbance which is characteristic of 'critical illness polyneuropathy'
      could be explained by a combination of the pure motor syndrome and the mild
      sensory neuropathy. More precise identification of the various neurophysiological
      abnormalities and aetiological factors may lead to further insights into the
      causes of neuromuscular weakness in the critically ill and ultimately to measures
      for their prevention and treatment.

PMID- 9757925
TI  - Risk factors for acute renal failure in trauma patients.
AB  - OBJECTIVE: To elucidate the risk factors for the development of acute renal
      failure (ARF) in severe trauma. DESIGN: Prospective observational study. SETTING:
      A general intensive care unit (ICU) of a university hospital. PATIENTS: A cohort
      of 153 consecutive trauma patients admitted to the ICU over a period of 30
      months. RESULTS: Forty-eight (31%) patients developed ARF. They were older than
      the 105 patients without ARF (p = 0.002), had a higher Injury Severity Score
      (ISS) (p < 0.001), higher mortality (p < 0.001), a more compromised neurological
      condition (p = 0.007), and their arterial pressure at study entry was lower (p =
      0.0015). In the univariate analysis, the risk of ARF increased by age, ISS > 17,
      the presence of hemoperitoneum, shock, hypotension, or bone fractures,
      rhabdomyolysis with creatine phosphokinase (CPK) > 10000 IU/l, presence of acute
      lung injury requiring mechanical ventilation, and Glasgow Coma Score < 10. Sepsis
      and use of nephrotoxic agents were not associated with an increased risk of ARF.
      In the logistic model, the need for mechanical ventilation with a positive end
      expiratory pressure > 6 cm H2O, rhabdomyolysis with CPK > 10000 IU/l, and
      hemoperitoneum were the three conditions most strongly associated with ARF.
      CONCLUSIONS: The identified risk factors for post-traumatic acute renal failure
      may help the provision of future strategies.

PMID- 9757926
TI  - The clinical relevance of the Waterlow pressure sore risk scale in the ICU.
AB  - OBJECTIVE: To evaluate whether the Waterlow pressure sore risk (PSR) scale has
      prognostic significance for intensive care patients. DESIGN: A prospective study.
      SETTING: The surgical intensive care unit (ICU) of the University Hospital
      Rotterdam. PATIENTS: Data were evaluated from 594 patients who had been admitted
      to the ICU during the year 1994. METHODS AND RESULTS: Each patient was assessed
      daily with respect to their Waterlow PSR score and the development of pressure
      sores in the sacral region. Actuarial statistical methods were used to analyse
      the predictive value of the risk score. When a patient had a Waterlow PSR score >
      25 on admission, the risk of developing a pressure sore was significantly
      increased compared to patients with a PSR score < 25. After admission, the daily
      Waterlow PSR scores obtained were significantly associated with the risk of
      developing a pressure sore. For each additional point this risk increased by 23%
      (95% confidence interval 17 to 28%). CONCLUSIONS: The Waterlow PSR scale provides
      the medical and nursing staff at an early stage with reliable information about
      the risk patients have in developing a pressure sore.

PMID- 9757927
TI  - Tracing best PEEP by applying PEEP as a RAMP.
AB  - OBJECTIVE: The aim of this study was to show the feasibility of a slow,
      continuously increasing level of positive end-expiratory pressure (PEEP) (ramp
      manoeuvre) in selecting best PEEP and to evaluate whether best PEEP, as defined
      by maximal oxygen transport, coincides with best systemic arterial oxygenation or
      best compliance. DESIGN: In 11 anaesthetized piglets, PEEP was increased between
      0 cmH2O (zero end-expiratory pressure; ZEEP) and 15 cmH2O (PEEP15) with a
      constant rate of 0.67 cmH2O x min(-1). This ramp manoeuvre was performed both
      under normal conditions and after induction of an experimental lung oedema.
      During the ramp manoeuvre, haemodynamic and pulmonary variables were monitored
      almost continuously. RESULTS: During the rise in PEEP, cardiac output declined in
      a non-linear way. In the series with normal conditions, best PEEP was always
      found at ZEEP. In the series with experimental lung oedema, best PEEP, as defined
      by maximum oxygen transport, was found at PEEP1-6, as defined by maximal
      compliance, at PEEP7.5 and by maximal arterial oxygen tension (PaO2) at PEEP10
      14. CONCLUSIONS: Best PEEP according to oxygen transport is lower than best PEEP
      according to compliance and PaO2; the use of PEEP as a ramp might prevent
      unnecessarily high levels of PEEP.

PMID- 9757928
TI  - Electrical impedance tomography in monitoring experimental lung injury.
AB  - OBJECTIVE: To apply electrical impedance tomography (EIT) and the new evaluation
      approach (the functional EIT) in monitoring the development of artificial lung
      injury. DESIGN: Acute experimental trial. SETTING: Operating room for animal
      experimental studies at a university hospital. SUBJECTS: Five pigs (41.3 +/- 4.1
      kg, mean body weight +/- SD). INTERVENTIONS: The animals were anaesthetised and
      mechanically ventilated. Sixteen electrodes were attached on the thoracic
      circumference and used for electrical current injection and surface voltage
      measurement. Oleic acid was applied sequentially (total dose 0.05 ml/kg body
      weight) into the left pulmonary artery to produce selective unilateral lung
      injury. MEASUREMENTS AND RESULTS: The presence of lung injury was documented by
      significant changes of PaCO2 (40.1 mmHg vs control 37.1 mmHg), PaO2 (112.3 mmHg
      vs 187.5 mmHg), pH (7.35 vs 7.42), mean pulmonary arterial pressure (29.2 mmHg vs
      20.8 mmHg) and chest radiography. EIT detected 1) a regional decrease in mean
      impedance variation over the affected left lung (-41.4% vs control) and an
      increase over the intact right lung (+ 20.4% vs control) indicating reduced
      ventilation of the affected, and a compensatory augmented ventilation of the
      unaffected lung and 2) a pronounced fall in local baseline electrical impedance
      over the injured lung (-20.6% vs control) with a moderate fall over the intact
      lung (-10.0% vs control) indicating the development of lung oedema in the injured
      lung with a probable atelectasis formation in the contralateral one. CONCLUSION:
      The development of the local impairment of pulmonary ventilation and the
      formation of lung oedema could be followed by EIT in an experimental model of
      lung injury. This technique may become a useful tool for monitoring local
      pulmonary ventilation in intensive care patients suffering from pulmonary
      disorders associated with regionally reduced ventilation, fluid accumulation
      and/or cell membrane changes.

PMID- 9757929
TI  - Anticoagulative effect of nitric oxide inhalation in ARDS.
AB  - Some studies have suggested that nitric oxide (NO) may cause platelet
      dysfunction. We present an ARDS patient who need this treatment, with a transient
      alteration of platelet function and a significant prolongation of bleeding time.

PMID- 9757931
TI  - Noise sources and levels in the Evgenidion Hospital intensive care unit.
AB  - Noise sources and levels were evaluated in a six-bed intensive care unit (ICU) in
      Athens, Greece. Ten patients (six males, four females) completed specifically
      designed questionnaires, and at the same time nine 8-h sound measuring sessions
      took place. A Bruel and Kjaer 2231 sound-meter was used on the decibel-A scale
      combined with observation. Human activity, operating equipment and construction
      engineering of the hospital building were identified as sources of noise. Noise
      levels were elevated [LEQ = 60.3-67.4 dB(A)]. No reliable information was
      obtained from the questionnaires. ICU noise levels were higher by 27 dB(A) than
      recommended hospitals levels. To counteract noise pollution in ICUs, staff
      awareness and sensitivity are needed.

PMID- 9757930
TI  - In vitro activity of fleroxacin against multiresistant gram-negative bacilli
      isolated from patients with nosocomial infections.
AB  - In order to evaluate the in vitro activity of fleroxacin against nosocomial gram
      negative organisms, 263 multiresistant gram-negative bacilli (203
      Enterobacteriaceae and 60 non-fermenting gram-negative bacilli) were isolated
      from adult patients with nosocomial infections. The different patterns of
      resistance to eight different antimicrobial agents (ampicillin, carbenicillin,
      piperacillin, cephalothin, cefamandole, ceftazidime, gentamicin and amikacin)
      were determined by minimum inhibitory concentration (MIC), using the agar
      dilution method. The most prevalent multiresistant species isolated were
      Klebsiella pneumoniae (28.9%), Escherichia coli (24%) and Pseudomonas aeruginosa
      (12.2%). All these bacterial strains showed three to five resistance patterns to
      at least three different antibiotics. Resistance to ceftazidime was observed in
      at least one of the resistance patterns of isolated bacteria. The activity of
      fleroxacin against multiresistant enteric bacteria was excellent; these strains
      showed a susceptibility of 79-100%. The susceptibility of P. aeruginosa to
      antipseudomonal agents was low; however, the activity of fleroxacin against these
      strains was higher than 60% (MIC < or = 2 microg/ ml), broadly comparable with
      ciprofloxacin. The resistance to fluoroquinolones detected in this study was no
      cause for alarm (3%). Consequently, fleroxacin maintains a remarkable activity
      against Enterobacteriaceae and remains highly active against other gram-negative
      bacilli. Nevertheless, actions directed at preventing or limiting resistance will
      be crucial to maintain the viability of fluoroquinolones as important therapeutic
      agents.

PMID- 9757933
TI  - A clinician's guide to the use of quality terminology. Working Group on Quality
      Improvement of the European Society of Intensive Care Medicine.

PMID- 9757935
TI  - Round table conference: acute lung injury, 15th-17th March 1997 Brussels,
      Belgium.

PMID- 9757932
TI  - Enteral nutrition in intensive care patients: a practical approach. Working Group
      on Nutrition and Metabolism, ESICM. European Society of Intensive Care Medicine.
AB  - Severe protein-calorie malnutrition is a major problem in many intensive care
      (ICU) patients, due to the increased catabolic state often associated with acute
      severe illness and the frequent presence of prior chronic wasting conditions.
      Nutritional support is thus an important part of the management of these
      patients. Over the years, enteral nutrition (EN) has gained considerable
      popularity, due to its favorable effects on the digestive tract and its lower
      cost and rate of complications compared to parenteral nutrition. However,
      clinicians caring for ICU patients are often faced with contradictory data and
      difficult decisions when having to determine the optimal timing and modalities of
      EN administration, estimation of patient requirements, and choice of formulas.
      The purpose of this paper is to provide practical guidelines on these various
      aspects of enteral nutritional support, based on presently available evidence.

PMID- 9757934
TI  - A European survey of the use of inhaled nitric oxide in the ICU. Working Group on
      Inhaled NO in the ICU of the European Society of Intensive Care Medicine.

PMID- 9757936
TI  - Kinetics of procalcitonin in iatrogenic sepsis.

PMID- 9757937
TI  - Prolonged high-dose administration of sodium nitroprusside in the intensive care
      unit.

PMID- 9757938
TI  - Survey of vasopressor usage.

PMID- 9757939
TI  - Postpartum brain death as a late fatal sequel of a previous skull base fracture.

PMID- 9757940
TI  - Two identical episodes of acute quadriparesia in an intensive care unit patient.

PMID- 9757941
TI  - Molecular cloning, expression and characterization of rhesus macaque Fas ligand
      cDNA.
AB  - The Fas/Fas ligand (FasL) interaction is pivotal in apoptosis-mediated regulation
      of the immune system. As such, it has relevance in areas of transplantation, gene
      therapy, AIDS, etc., all of which utilize the rhesus macaque as a preclinical
      animal model. In order to examine rhesus Fas/FasL, we cloned the rhesus FasL cDNA
      and have analyzed the function of the cloned gene. Our findings indicate that the
      rhesus FasL is highly homologous to the human but not the mouse (97% for human,
      85% for mouse). In addition, soluble rhesus FasL can induce apoptosis, a property
      shared with the human soluble protein but not the mouse protein. The deduced
      protein sequence is 280 amino acids with a calculated Mr. of 31,646. Transfection
      of COS cells with the full-length cDNA yielded a 40 KD protein, which is in
      agreement with the size of human FasL. COS cells expressing rhesus FasL induced
      apoptosis in rhesus PHA blasts and human Fas+ CEM-6 cells. Thus, the cloned
      rhesus macaque FasL is functional and cross-reacts with human Fas. The cloned
      functional rhesus FasL cDNA will enable studies of its regulatory role in the
      nonhuman primate immune system.

PMID- 9757942
TI  - The CLIP-substituted invariant chain efficiently targets an antigenic peptide to
      HLA class II pathway in L cells.
AB  - The presentation of antigenic peptides by major histocompatibility complex (MHC)
      class II to CD4+ T cells is crucial to initiate immune responses. We developed a
      new system for delivery of an antigenic peptide to the MHC class II pathway,
      using the invariant chain (Ii). We designed a mutated human p33-form Ii, CLIP
      substituted Ii, in which streptococcal M12p55-68 (RDLEQAYNELSGEA) was substituted
      for CLIP (class II associated invariant chain peptide). We examined the peptide
      presenting function of this construct, in comparison with the previously reported
      C-terminal fused Ii, in which a cathepsin cleavage site and M12p54-68 was ligated
      to the C-terminus of Ii. Mouse L cell transfectants expressing either of these
      two mutated Ii along with HLA-DR4 could process and present M12p55-68 to the
      peptide specific and DR4-restricted CD4+ T cell clone. CLIP-substituted Ii was
      much more efficient in antigen presentation than was the C-terminal fused Ii.
      Similar to the wild-type Ii, the CLIP-substituted Ii was associated
      intracellularly with DR4 molecules. These results indicate that the peptide
      substituted for CLIP of Ii p33 bound to the groove of DR molecules in the same
      manner as CLIP and it was preferentially presented to the CD4+ T cell clone in
      the absence of HLA-DM molecules. This system may prove useful for immunotherapy
      with DNA vaccines or for construction of an antigen presenting cell library with
      diverse peptides.

PMID- 9757943
TI  - Interleukin 2 receptor regulation and IL-2 function in the human infant.
AB  - IL-2 receptor is expressed at low levels on adult blood lymphocytes, and at lower
      levels on cord blood cells. IL-2 receptor alpha and beta chain expression
      increases gradually from 0-18 months of age. The level of soluble CD25 (IL-2
      receptor alpha chain) has been reported to be elevated in cord blood.
      Quantitative RT-PCR showed that adult cells express 10 times as much CD25 mRNA as
      cord cells. Cord plasma showed only a marginal ability to strip CD25 from the
      membrane. To assess the functional consequences of low IL-2 receptor expression,
      cord and adult cells were activated in vitro. The response was stimulus
      dependent, but cord cells upregulated CD25 readily. Cord and adult cells
      proliferated in an IL-2-dependent assay to a similar extent. Infants suffering
      acute infection showed marginally higher levels of membrane CD25 expression than
      infants without overt infection. Thus neonatal and infant lymphocytes express
      lower levels of IL-2 receptors than adult cells, reflecting lower mRNA
      concentrations at least for CD25; they are able to up-regulate receptors in
      response to in vitro stimulation and are able to respond in vitro to IL-2
      dependent stimulation; however in vivo there may be a dampening down of the IL-2
      system in infancy.

PMID- 9757944
TI  - Generation of stable monocyte-derived dendritic cells in the presence of high
      concentrations of homologous or autologous serum: influence of extra-cellular pH.
AB  - Recent studies have highlighted the high degree of differentiation of monocytes.
      Indeed, dendritic cells (DC) can be generated from monocytes, in the presence of
      appropriate cytokines. However, human serum is usually avoid in such cultures.
      Here, we report that human serum does not inhibit generation of mature DC from
      blood monocytes, but rather that extra-cellular pH may play an important role in
      the regulation of monocyte differentiation. Indeed, monocytes cultured at pH 7.4
      in the presence of high concentrations of human serum developed efficiently into
      mature DC, as opposed with monocytes cultured at pH 7. These pH 7.4 cultured DC
      presented features characteristic of mature DC, at the phenotypical, functional
      and morphological levels. In addition, these DC were stable, with respect to
      their sustained expression of CD83 and CD86, upon withdrawal of cytokines.
      Finally, when autologous plasma was used instead of homologous serum,
      differentiation of monocytes into mature DC was efficient, as well. Thus,
      altogether, our data show the importance of extra-cellular pH on differentiation
      of monocyte-derived DC in the presence of human serum, which should be maintained
      at plasma levels.

PMID- 9757945
TI  - T cell responses to 53-kDa outer membrane protein of Porphyromonas gingivalis in
      humans with early-onset periodontitis.
AB  - Patients with early-onset periodontitis (EOP) are susceptible to infection with
      periodontopathic bacteria, such as Porphyromonas gingivalis. Ag53, 53-kDa outer
      membrane protein of P. gingivalis, evokes strong humoral immune responses in EOP
      patients. In a first step to clarify how host immune cells recognize Ag53, we
      established Ag53-specific short-term T cell lines from 22 subjects including 6
      EOP patients and 16 healthy donors, using overlapping peptides based on Ag53
      amino acid sequences. All T cell lines from active EOP patients recognized a
      common region (p141-181, especially p141-161) on Ag53, while those from healthy
      donors showed heterogeneous specificity. p141-181 was not recognized by T cell
      lines established from EOP patients following therapy. A monoclonal antibody to
      HLA-DRB 1 inhibited Ag53-induced proliferation of most of the T cell lines. Our
      observations suggest that, although antigen-presenting molecules are common in
      EOP patients and in healthy individuals, p141-161 includes a major T cell
      epitope(s) on Ag53 for active EOP patients but not for healthy individuals or
      inactive EOP patients.

PMID- 9757946
TI  - Soluble HLA-I in rheumatic diseases.
AB  - OBJECTIVE: To study serum levels of Class I soluble HLA (sHLA-I) in patients with
      systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), polymyositis or
      dermatomyositis (PM/DM) or scleroderma and to assess the possible influence of
      ethnic factors on concentration in each disease group. METHODS: Solid-phase
      enzyme linked immunoassay was used to measure sHLA-I in the serum of 385 patients
      with varied ethnic backgrounds (American-Caucasians, African-Americans, Georgian
      Caucasians) with rheumatic diseases. Studies on patients were compared to similar
      measurements of 189 healthy individuals. RESULTS: Mean sHLA-I levels were
      significantly higher in patients with SLE than those observed in healthy
      individuals or other rheumatic diseases. Highest concentrations were present in
      Georgian-Caucasian patients with SLE. American-Caucasian patients with RA or
      scleroderma had higher sHLA-I levels than normal Caucasian individuals. The
      majority of patients with PM/DM in all ethnic subgroups were low secretors of
      sHLA-I. CONCLUSION: Mechanisms underlying the secretion of sHLA-I appear to
      differ among the rheumatic diseases studied and various ethnic groups. These
      genetic differences in sHLA-I secretion could be associated with ethnic and
      pathophysiologic differences among these rheumatic diseases.

PMID- 9757947
TI  - Impact of the MHC-encoded HLA-DMA, DMB, and LMP2 gene polymorphisms on kidney
      graft outcome.
AB  - We previously studied the relationship between TAP1 and TAP2 gene polymorphism
      and compatibility in kidney graft outcome and reported that the currently
      described TAP1 and TAP2 gene polymorphisms did not influence the incidence of
      acute rejection episodes. In this study, we report on the effect of polymorphism
      and matching of HLA-DMA, -DMB, and LMP2 genes on kidney graft outcome. This study
      was performed on 102 selected kidney recipients who experienced two or more acute
      rejection episodes (rejection group) during follow up and who were compared to a
      group of 150 patients who never had rejection (non rejection group). Although a
      significant effect of HLA-DR matching was observed between these two groups, our
      data suggest that matching for all the new genes located in the HLA class II
      region (TAP1, TAP2, LMP2, HLA-DMA and -DMB) does not influence the kidney graft
      outcome. However, a significant increase (pc < 0.05) of DMA*0102 allele was
      observed in the recipients of the rejection group as compared to those of the non
      rejection group. This effect was not due to a linkage disequilibrium between DMA
      and HLA-DR loci and suggests that this specific HLA-DMA allele could play a role
      in the indirect pathway of class II presentation of donor antigens.

PMID- 9757949
TI  - A new categorization of HLA DR alleles on a functional basis.
AB  - In this analysis, we introduce a new categorization of HLA DR alleles which are
      important members of HLA class II genes encoding cell surface glycoproteins that
      function to present antigenic peptides to T cells. We have grouped all HLA DR
      molecules into seven different functional categories on the basis of their
      ability to bind and present antigenic peptides to T cells and their association
      with susceptibility or resistance to disease. This novel categorization of DR
      alleles on the basis of function allows for the prediction of seven similar
      subregion structures (supertypes or supermotifs) within pocket 4 of HLA DR
      peptide binding groove as the molecular basis for grouping these alleles. The
      physicochemical characteristics of HLA DR supertype residues, charge in
      particular, may influence the selectivity for binding peptide, dominate
      promiscuous T-cell recognition of antigenic peptides, and affect HLA DR disease
      associations. To rationalize the functional categories of DR alleles, we have
      further combined the seven DR supertype patterns into three groups based on the
      charges of residues within the supertypes. Grouping HLA DR alleles into
      functional categories may assist in understanding the mechanistic basis of
      autoimmunity, resolving current paradoxes in HLA disease associations, and
      developing new immunotherapy strategies.

PMID- 9757950
TI  - Nomenclature for factors of the HLA system, update April 1998. WHO Nomenclature
      Committee for Factors of the HLA System.

PMID- 9757948
TI  - Characterization and distribution of Mhc-DPB1 alleles in chimpanzee and rhesus
      macaque populations.
AB  - Allelic diversity at the nonhuman primate Mhc-DPB1 locus was studied by
      determining exon 2 nucleotide sequences. This resulted in the detection of 17
      chimpanzee (Pan troglodytes), 2 orangutan (Pongo pygmaeus) and 16 rhesus macaque
      (Macaca mulatta) alleles. These were compiled with primate Mhc-DPB1 nucleotide
      sequences that were published previously. Based upon the results, a sequence
      specific oligotyping method was developed allowing us to investigate the
      distribution of Mhc-DPB1 alleles in distinct chimpanzee and rhesus macaque
      colonies. Like found in humans, chimpanzee and rhesus macaque populations
      originating from different geographic backgrounds appear to be characterized by
      the presence of a few dominant Mhc-DPB1 alleles.

PMID- 9757951
TI  - Nomenclature for factors of the HLA system, update May/June 1998. WHO
      Nomenclature Committee for Factors of the HLA System.

PMID- 9757952
TI  - Endometrial carcinoma after endometrial ablation: high-risk factors predicting
      its occurrence.
AB  - Our purpose was to review reported cases of endometrial carcinoma after
      endometrial ablation and to evaluate high-risk factors predicting its occurrence.
      We present guidelines for the treatment of abnormal uterine bleeding unresponsive
      to medical therapy in this high-risk group of patients. Eight detailed reports on
      endometrial carcinoma after endometrial ablation were reviewed. The indications,
      methods of treatment, follow-up, and associated high-risk factors for endometrial
      carcinoma were analyzed. A focused list of high-risk factors for endometrial
      carcinoma was developed on the basis of the data collected. Guidelines were
      established to enable surgeons to minimize the risks of subsequent uterine cancer
      in women with abnormal uterine bleeding that is unresponsive to medical therapy
      (ie, candidates for ablation). Women who had endometrial carcinoma develop after
      ablation had predictive high-risk factors for subsequent neoplasia, and all
      eventually underwent a hysterectomy. Women with abnormal uterine bleeding and
      high-risk factors for endometrial carcinoma who did not respond to medical
      treatment may safely undergo endometrial ablation but must have a preablation
      biopsy indicating normal endometrium. Persistent hyperplasia unresponsive to
      hormonal therapy should influence the selection of a hysterectomy. Careful
      screening of patients before undergoing endometrial destructive procedures is
      prescient because minimally invasive, nonhysteroscopic ablative techniques are
      now emerging.

PMID- 9757953
TI  - Routine maternal platelet count: an assessment of a technologically driven
      screening practice.
AB  - Because automated blood cell counters are now widely used in many clinical
      settings, an assessment of hemoglobin concentration or hematocrit is invariably
      accompanied by a platelet count. Thus many asymptomatic pregnant women are being
      screened for thrombocytopenia. The objective of a good screening program is to
      reduce morbidity and mortality and thereby improve the quality of life; criteria
      for the evaluation of proposed or ongoing screening programs are well
      established. However, the screening of pregnant women for thrombocytopenia seems
      to have been both technologically mandated and passively accepted. Therefore we
      systematically evaluated the current de facto screening of asymptomatic pregnant
      patients for thrombocytopenia in the context of well-explained, desirable
      characteristics for a successful screening program. We conclude that screening
      for thrombocytopenia in pregnancy fails to meet established criteria, may
      actually be harmful (by placing unaffected fetuses of thrombocytopenic women, and
      the women themselves, at risk from invasive procedures), and should therefore be
      discontinued.

PMID- 9757954
TI  - Oral contraceptive discontinuation: a prospective evaluation of frequency and
      reasons.
AB  - OBJECTIVES: Our purpose was to define the frequency and reasons for oral
      contraceptive discontinuation and subsequent contraceptive behavior. STUDY
      DESIGN: A nationwide prospective study of 1657 women initiating or switching to
      the use of a new contraceptive from private practices, clinics, and a health
      maintenance organization was performed. RESULTS: Six months after a new oral
      contraceptive prescription, 68% of new starts and 84% of switchers still used
      oral contraceptives. Of women who discontinued, 46% did so because of side
      effects, whereas 23% had no continuing need. More than four fifths of women who
      discontinued oral contraceptives but remained at risk of unintended pregnancy
      either failed to adopt another method or adopted a less effective method. Fifteen
      percent of women who discontinued oral contraceptives resumed their use within
      the 7-month follow-up period. CONCLUSIONS: Counseling should emphasize the
      possibility of side effects, stressing the fact that most will be transient, and
      the need to identify a backup method. Follow-up visits should be scheduled for 1
      to 2 months after a prescription is written.

PMID- 9757955
TI  - Compliance with depot medroxyprogesterone acetate: a randomized, controlled trial
      of intensive reminders.
AB  - We enrolled women in a prospective, randomized study to determine whether an
      intensive reminder system would improve compliance in women receiving depot
      medroxyprogesterone injections. Women selecting this treatment were assigned to a
      group that received both mail and telephone reminders or to a second group that
      received only a scheduled appointment at the time of the previous injection. The
      rate of continuation and the rate of on-time injections did not differ between
      groups. Women who had prolonged bleeding were more likely to discontinue depot
      medroxyprogesterone injections.

PMID- 9757956
TI  - Osteitis pubis after Marshall-Marchetti-Krantz urethropexy: a pubic
      osteomyelitis.
AB  - OBJECTIVE: Our purpose was to review cases of osteitis pubis encountered at our
      institution after Marshall-Marchetti-Krantz retropubic urethropexy. STUDY DESIGN:
      The charts of patients diagnosed with osteitis pubis subsequent to Marshall
      Marchetti-Krantz retropubic urethropexy from 1980 to 1994 were reviewed. RESULTS:
      Fifteen cases of osteitis pubis were diagnosed after 2030 Marshall-Marchetti
      Krantz procedures (0.74%). Onset of symptoms related to osteitis pubis began a
      mean of 69.8 days postoperatively (range 10 to 459 days). Although initial plain
      films of the symphysis pubis were normal in 7 (54%), radiographic abnormality was
      eventually demonstrated in all a mean of 25.7 weeks after surgery (range 4 to 78
      weeks). A variety of conservative treatments resulted in symptomatic relief in
      47%. Seven of the remaining patients underwent operative therapy with partial or
      complete relief noted in all. Subsequent bone cultures were positive in 5 (71%).
      At follow-up a mean of 58 months after the Marshall-Marchetti-Krantz procedure
      complete resolution of symptoms was noted in 33% and continued pain or ambulatory
      difficulty in the remainder. There was no relationship between postoperative
      urinary tract infections, postoperative complications, presenting sign of fever,
      elevated leukocyte count or sedimentation rate, and subsequent operative
      intervention (P > .05). CONCLUSIONS: Osteitis pubis after urogynecologic surgery
      is an uncommon event requiring aggressive surgical and antibiotic therapy. When
      bone cultures are performed, a microbial cause may be demonstrated in as many as
      71% of patients.

PMID- 9757958
TI  - Further evidence that the WT1 gene does not have a role in the development of the
      derivatives of the mullerian duct.
AB  - OBJECTIVE: Several lines of evidence suggest that expression of the WT1
      transcription factor gene is necessary for normal development of the renal and
      male reproductive systems. Female patients with severe reproductive tract
      developmental defects were examined for WT1 gene mutations. STUDY DESIGN: The WT1
      gene was analyzed in 25 patients with congenital absence of the uterus and vagina
      for mutations. Genomic deoxyribonucleic acid prepared from blood leukocytes was
      subjected to Southern blot analysis and denaturing gradient gel electrophoresis.
      RESULTS: Common WT1 gene deoxyribonucleic acid sequence polymorphisms were found
      in both normal control subjects and patients with congenital absence of the
      uterus and vagina. No deoxyribonucleic sequence differences or mutations likely
      to cause congenital absence of the uterus and vagina were detected in the
      patients. CONCLUSIONS: The absence of WT1 gene mutations in patients with
      congenital absence of the uterus and vagina supports the hypothesis that WT1
      expression is required only for later urogenital development, after the
      mesonephric and paramesonephric ducts have already formed.

PMID- 9757957
TI  - Telomere shortening in uterine leiomyomas.
AB  - OBJECTIVE: To gain a better understanding of proliferation control mechanisms in
      a common benign tumor, we investigated the mean telomere length and the clonality
      of uterine leiomyomas. STUDY DESIGN: Deoxyribonucleic acid from uterine
      leiomyomas and from the adjacent normal myometrium of 51 patients (total number
      of uterine leiomyomas 107; 28 patients with single leiomyoma, 23 patients with
      multiple leiomyomas ranging from 2 to 8 myoma nodules per case) was hybridized to
      a telomeric oligonucleotide probe by Southern blot and chemiluminescent
      detection. The mean telomere length was evaluated by densitometry. Clonality was
      assessed with use of the phosphoglycerokinase gene polymorphism. RESULTS: The
      mean telomere length was significantly shorter in uterine leiomyomas (median 7950
      bp, interquartile range 7261 to 8372 bp) than in normal myometrium (median 9688
      bp, interquartile range 8528 to 10535 bp) (P < .001). There was no correlation
      between tumor size and telomere attrition. Multiple uterine leiomyomas were found
      to have an independent clonal origin. CONCLUSIONS: Telomere attrition in uterine
      leiomyomas reflects enhanced proliferation activity in the course of tumor
      evolution. The basic telomere lengths differ in the myocytes from which the
      uterine leiomyomas originate, probably explaining the lack of correlation between
      telomere attrition and tumor size.

PMID- 9757959
TI  - Methotrexate effects on trophoblast and the corpus luteum in early pregnancy.
AB  - OBJECTIVE: Our purpose was to determine whether methotrexate affects the
      trophoblast or corpus luteum when administered for abortion. STUDY DESIGN: A
      randomized controlled trial was performed in women requesting an abortion up to
      49 days' gestation. Twenty patients were treated with intramuscular methotrexate
      50 mg/m2 (10 women) or 60 mg/m2 (10 women). Serum beta-human chorionic
      gonadotropin, progesterone, and 17-hydroxyprogesterone levels were determined at
      baseline and then serially after methotrexate administration for the first 24
      hours, then every 24 hours for 7 days. On the seventh day misoprostol 800 microg
      was administered vaginally. RESULTS: Serum beta-human chorionic gonadotropin
      increased at a lower rate than occurs in normal pregnancy. Progesterone levels
      averaged 56.9 +/- 19.8 nmol/L at baseline and 45.5 +/- 20.5 nmol/L (P = .01) 1
      week after methotrexate. Progesterone decreased in 16 women over the 7 days and
      increased in the other 4; these latter women all aborted after a single dose of
      misoprostol. Levels of 17-hydroxyprogesterone plateaued during the first day
      after methotrexate administration; both progesterone and 17-hydroxyprogesterone
      declined simultaneously between the third and fourth day after methotrexate.
      CONCLUSIONS: Methotrexate most likely primarily affects trophoblast production of
      human chorionic gonadotropin, as evidenced by a blunting of the expected increase
      in serum beta-human chorionic gonadotropin resulting in less support for the
      production of progesterone by the corpus luteum. However, changes in progesterone
      levels after methotrexate administration were inconsistent and are unlikely to
      represent the ultimate effect of methotrexate in abortion. The less-than-normal
      increase in serum beta-human chorionic gonadotropin levels after methotrexate
      administration is most likely a result of disruption of cytotrophoblast
      syncytialization. This disruption may be the true effect of methotrexate in
      destabilizing the implantation site of an early pregnancy.

PMID- 9757961
TI  - Oxytocin receptor and its messenger ribonucleic acid in human leiomyoma and
      myometrium.
AB  - OBJECTIVE: The study determined the expression of oxytocin receptor and its gene
      in human uterine leiomyoma compared with the adjacent myometrium. STUDY DESIGN:
      Paired samples of leiomyoma and the adjacent myometrium from 20 women through the
      menstrual cycle, menopause, and various hormone treatments were studied. Oxytocin
      receptor was immunohistochemically localized with use of the specific antibody
      (2F8) to human oxytocin receptor. Oxytocin receptor protein was determined by
      Western blotting, whereas reverse transcription-polymerase chain reaction was
      used for oxytocin receptor messenger ribonucleic acid expression. RESULTS:
      Immunohistochemistry showed positive staining in all tissues examined, relatively
      more intense in the myometrium than in the adjacent leiomyoma, and in tissues
      from the preovulatory than the postovulatory phase. Western blotting showed a
      single 70-kd band corresponding to the oxytocin receptor. The relative abundance
      of oxytocin receptor in both leiomyoma and myometrium was significantly higher
      during the preovulatory (n = 5) than the postovulatory (n = 5) phase (P = .034
      and .05). In women receiving gonadotropin-releasing hormone agonist (n = 1) or
      oral contraceptives (n = 1), after the menopause (n = 2), and with irregular
      vaginal bleeding (n = 1), oxytocin receptor levels in leiomyoma and myometrium
      were unchanged but were reduced in anovulatory cycles (amenorrhea, n = 2).
      Reverse transcription-polymerase chain reaction showed messenger ribonucleic acid
      for oxytocin receptor as a 391-bp band in all leiomyomas and myometrium examined.
      CONCLUSIONS: Leiomyoma and myometrium express the gene and protein for oxytocin
      receptor, which is probably partially regulated by ovarian sex steroids during
      the menstrual cycle.

PMID- 9757962
TI  - Genetic differentiation of complete hydatidiform moles coexisting with normal
      fetuses by short tandem repeat-derived deoxyribonucleic acid polymorphism
      analysis.
AB  - OBJECTIVE: We applied deoxyribonucleic acid polymorphism analysis on the basis of
      differences in the number of short tandem repeat sequences to genetically
      differentiate dizygotic twins with complete hydatidiform moles and normal fetuses
      from partial moles presenting a similar appearance. STUDY DESIGN: Six pregnant
      women exhibiting apparent moles and coexisting fetuses were the subjects of this
      study. Eight polymorphic loci including short tandem repeat sequences were
      amplified by polymerase chain reaction from deoxyribonucleic acid of peripheral
      leukocytes of parents, umbilical cord, grossly normal placenta-villi, and molar
      tissue. The segregation of alleles among samples were determined by comparing
      band patterns on polyacrylamide gels. RESULTS: In all 6 cases amplifications of
      polymorphic loci provided sufficient information to determine the parental
      origin. At informative loci the alleles of cord and placenta-villi were
      transmitted from both patients and husbands whereas molar tissue had only
      paternal alleles. These allele segregations indicated 2 different genetic
      origins, namely, normal parental for a fetus and androgenetic for molar tissue,
      and thus the diagnosis of dizygotic twins with a complete hydatidiform mole and a
      normal fetus was made. Additionally, the molar component was defined as a
      heterozygous mole in 2 cases. CONCLUSION: Short tandem repeat-derived
      deoxyribonucleic acid polymorphism analysis was demonstrated to be a useful and
      precise procedure for the differential diagnosis of a complete hydatidiform
      coexisting with a normal fetus and the determination of its zygosity as well.

PMID- 9757960
TI  - The sequential effects of estrogen administration and hypertension on cardiac
      function in ewes.
AB  - OBJECTIVE: Our objective was to study the effect of estrogen administration and
      moderate hypertension on left ventricular size, pump function, and contractility
      in chronically instrumented ewes. STUDY DESIGN: Ewes were either given 0.06 mg/kg
      17beta-estradiol intramuscularly (n = 8) or were made hypertensive (n = 6) by
      inflation of an occluder around the aorta and were studied weekly. After 3 weeks
      each ewe received the opposite treatment. RESULTS: Estrogen administration caused
      an increase in left ventricular chamber size at a given pressure, fractional
      shortening (21.9% +/- 2.9% to 28.5% +/- 3.7%), and stroke volume (1.4 +/- 0.3
      mL/kg to 1.6 +/- 0.3 mL/kg). Subsequent hypertension further increased left
      ventricular size at a given pressure but decreased fractional shortening (20.0%
      +/- 4.4%) and stroke volume (1.3 +/- 0.3 mL/kg). With hypertension first, there
      was no left ventricular enlargement, even with subsequent estrogen
      administration, and there were no changes in left ventricular pump function. End
      systolic pressure and stress-dimension relationships did not change with either
      treatment. The end-systolic wall stress-fractional shortening relationship was
      likewise unchanged, suggesting that neither treatment changed contractility.
      CONCLUSIONS: The left ventricle previously exposed to hypertension does not
      remodel when exposed to estrogen, and cardiac pump function decreases when the
      estrogen enlarged heart is faced with moderate, subacute hypertension.

PMID- 9757963
TI  - International multicenter term PROM study: evaluation of predictors of neonatal
      infection in infants born to patients with premature rupture of membranes at
      term. Premature Rupture of the Membranes.
AB  - OBJECTIVE: Our objective was to determine significant predictors for the
      development of neonatal infection in infants born to patients with premature
      rupture of membranes at term. STUDY DESIGN: Multivariate analysis was used to
      determine the significant predictors of neonatal infection in infants born to
      women with premature rupture of the membranes who were enrolled in the Term PROM
      Study. In a randomized, controlled trial, the Term PROM Study recently compared
      induction of labor with expectant management for premature rupture of membranes
      at term. RESULTS: The following variables were identified as independent
      predictors of neonatal infection: clinical chorioamnionitis (odds ratio 5.89, P <
      .0001), positive maternal group B streptococcal status (vs negative or unknown,
      odds ratio 3.08, P < .0001), 7 to 8 vaginal digital examinations (vs 0 to 2, odds
      ratio 2.37, P = .04), 24 to < 48 hours from membrane rupture to active labor (vs
      < 12 hours, odds ratio 1.97, P = .02), > or = 48 hours from membrane rupture to
      active labor (vs < 12 hours, odds ratio 2.25, P = .01), and maternal antibiotics
      before delivery (odds ratio 1.63, P = .05). CONCLUSIONS: Among infants born to
      patients with premature rupture of membranes at term, clinical chorioamnionitis
      and maternal colonization with group B streptococci are the most important
      predictors of subsequent neonatal infection.

PMID- 9757964
TI  - Treating ectopic pregnancy with the combination of mifepristone and methotrexate:
      a phase II nonrandomized study.
AB  - OBJECTIVE: Our goal was to compare the use of a combination of methotrexate and
      mifepristone with methotrexate alone in the medical management of ectopic
      pregnancy. STUDY DESIGN: This was a preliminary nonrandomized phase II study. All
      patients with progressing ectopic pregnancy meeting criteria for medical
      management were included. Treatment consisted of 50 mg/m2 of methotrexate
      injected intramuscularly and 600 mg of mifepristone, administered orally,
      compared with a previous group who received only 50 mg/m2 of methotrexate
      injected intramuscularly. RESULTS: Of the 30 patients treated with the
      combination, there was only 1 failure, whereas medical treatment had failed for
      11 of 42 patients treated with methotrexate alone. CONCLUSIONS: The combination
      of mifepristone and methotrexate decreased the risk of failure in medical
      treatment of ectopic pregnancy.

PMID- 9757965
TI  - Interleukin-1beta and interleukin-8 in cervicovaginal fluid during pregnancy.
AB  - OBJECTIVE: We investigated the usefulness of cervicovaginal interleukin-1beta and
      interleukin-8 levels during pregnancy as markers of preterm and term parturition.
      STUDY DESIGN: Cervicovaginal fluids were obtained from 119 pregnant women at 24
      to 41 weeks' gestation. Cytokine concentrations were measured by enzyme-linked
      immunoassay. RESULTS: Interleukin-1beta and interleukin-8 concentrations in
      cervicovaginal fluids obtained from women not in labor increased exponentially as
      gestational age increased. Interleukin-1beta and interleukin-8 concentrations
      were significantly correlated. These cytokine concentrations were significantly
      higher in patients in preterm labor than in patients at preterm not in labor and
      were significantly higher in women at term in labor than in women at term not in
      labor. These cytokine levels were significantly correlated with the degree of
      cervical dilation and tocolytic index. CONCLUSIONS: These findings suggest that
      cervicovaginal interleukin-1beta and interleukin-8 contribute to term and preterm
      parturition. Measurement of cervicovaginal concentrations of these cytokines may
      be clinically useful in patients with threatened premature delivery.

PMID- 9757966
TI  - Evaluating rapid diagnostic tests of intra-amniotic infection: Gram stain,
      amniotic fluid glucose level, and amniotic fluid to serum glucose level ratio.
AB  - OBJECTIVE: The aim of the study was to compare the diagnostic utility of the Gram
      stain, the amniotic fluid glucose level, and the ratio of amniotic fluid glucose
      level to serum glucose level in detecting intra-amniotic infection. STUDY DESIGN:
      We conducted a prospective study of 127 patients with preterm labor and 26
      patients with preterm premature rupture of the membranes (153 total). All
      patients underwent amniocentesis to diagnose intra-amniotic infection. The
      diagnostic criterion for intra-amniotic infection was a positive amniotic fluid
      culture result. RESULTS: The Gram stain is 80% sensitive and 91% specific when a
      positive is considered the presence of white blood cells or bacteria. Amniotic
      fluid glucose level and the ratio of amniotic fluid glucose level to serum
      glucose level are significantly lower when amniotic fluid culture results are
      positive, but as diagnostic tests they are inferior to the Gram stain. Logistic
      regression models that combine predictors yield superior accuracy with respect to
      individual tests. The most accurate combination was amniotic fluid glucose level
      and Gram stain with white blood cells or bacteria. Although the number of
      patients with preterm premature rupture of the membranes was small in this study
      (n = 26), analysis of our data suggests that the diagnostic performance levels of
      these tests were similar when used in patients with preterm labor and intact
      membranes and in patients with premature rupture of the membranes. CONCLUSIONS:
      The amniotic fluid glucose level and the ratio of amniotic fluid to serum glucose
      level have equivalent diagnostic utility and are inferior to the Gram stain. The
      combination of Gram stain with amniotic fluid glucose level is superior to any
      individual test.

PMID- 9757967
TI  - Declining cesarean delivery rates in California: an effect of managed care?
AB  - OBJECTIVES: We hypothesized that movement from traditional indemnity insurance to
      managed care in California between 1983 and 1994 would lead to reductions in the
      rate of cesarean delivery. STUDY DESIGN: We decomposed the frequency of cesarean
      delivery with each primary diagnosis into the product of the diagnosis rate among
      all women and the cesarean delivery rate among women with the given diagnosis
      (conditional cesarean delivery rate). We used logistic regression to estimate the
      diagnosis and conditional cesarean delivery rates. RESULTS: Adjusted and observed
      cesarean delivery rates are indistinguishable. Both the diagnosis rates and the
      conditional cesarean delivery rates contributed to the increase in the cesarean
      delivery rate between 1983 and 1987. The subsequent decline is attributable to
      the decline in the repeated cesarean delivery rate. CONCLUSIONS: The increase in
      managed care in California played no apparent role in the decline in the cesarean
      delivery rate. With the exception of Kaiser health maintenance organizations,
      managed care providers and indemnity insurers managed deliveries similarly.

PMID- 9757968
TI  - Serum from preeclamptic women induces vascular cell adhesion molecule-1
      expression on human endothelial cells in vitro: a possible role of increased
      circulating levels of free fatty acids.
AB  - OBJECTIVE: The object was to determine whether serum from preeclamptic women
      induces expression of vascular cell adhesion molecule-1 on cultured endothelial
      cells. STUDY DESIGN: Endothelial cells were incubated with medium containing 20%
      serum (volume/volume) either from women with preeclampsia (n = 15) or from women
      with normal pregnancies (n = 15) matched for maternal age, gestational age, and
      parity. A further matched set of samples (n = 10) was exposed to endothelial
      cells that had previously been incubated in the presence or absence of vitamin E
      (40 micromol/L final concentration). Free fatty acids were determined in each
      sample. A mixture of free fatty acids (linoleic, oleic, and palmitic acids,
      1:1:1) was added to serum from control subjects in increasing concentrations (70
      280 micromol/L final concentration) to emulate preeclamptic serum and the
      preparation was exposed to endothelial cells. In each experiment vascular cell
      adhesion molecule-1 expression was determined after 16 hours of exposure by an
      enzyme-linked immunosorbent assay technique performed on the cell monolayer.
      RESULTS: Preeclamptic serum had higher levels of free fatty acids than did that
      of control subjects (0.71 mmol/L, 95% confidence level 0.5-0.93, vs 0.36 mmol/L,
      95% confidence level 0.28-0.43). There was a statistically significant increase
      in vascular cell adhesion molecule-1 expression on the endothelial cells exposed
      to preeclamptic serum compared with those exposed to control serum (optical
      density 0.17 vs 0.11). Vitamin E reduced the vascular cell adhesion molecule-1
      expression of endothelial cells exposed both to preeclamptic and to control serum
      samples in a nonspecific manner. Addition of free fatty acids to normal pregnancy
      serum to mimic the effect of preeclampsia resulted in increased expression of
      vascular cell adhesion molecule-1 on the cells. CONCLUSION: Preeclamptic serum
      induces vascular cell adhesion molecule-1 expression on human endothelial cells
      in vitro, an effect also produced by fatty acids. The elevated level of free
      fatty acids in women with preeclampsia may contribute to increased vascular cell
      adhesion molecule expression in vivo.

PMID- 9757970
TI  - Group B streptococci during pregnancy: a comparison of two screening and
      treatment protocols.
AB  - OBJECTIVE: The objective was to evaluate whether the rate of neonatal group B
      streptococcal infection could be reduced by screening for group B streptococci
      during the third trimester of pregnancy. STUDY DESIGN: Two periods in which
      different screening and treatment protocols were applied were compared. In period
      A all mothers showing high-risk factors were given peripartal antibiotic
      coverage. In period B vaginal and rectal smears were routinely obtained in
      gestational week 34 and cultured for group B streptococci. If culture results
      were positive, the woman received peripartal antibiotics. The incidence of group
      B streptococcal infections and the number of peripartal antibiotic doses were
      established by comparing 3700 neonates (3623 mothers) in period A with 3648
      neonates (3569 mothers) in period B. RESULTS: In period A, 20 group B
      streptococcal infections were recorded. Of these, 5 were severe to life
      threatening. In period B, 4 group B streptococcal infections were observed. Two
      were severe and occurred in neonates born before the mothers could be screened.
      Another 2 were mild and occurred in neonates whose mothers had negative screening
      test results. The reduction was significant by the chi2 test (chi2 = 9.19, Yates'
      corrected P = .0024). The rates of peripartal antibiotic treatment were 11.9% in
      period A and 14.5% in period B. CONCLUSION: Although no neonate died of group B
      streptococcal sepsis in either of the 2 periods, the protocol used in period B
      clearly reduced the incidence of group B streptococcal infection. The number of
      peripartal antibiotic doses required was not much higher than in period A.
      Screening for group B streptococci in week 34 seems to be a valuable contribution
      to further improvement of neonatal outcome.

PMID- 9757971
TI  - How small is too small in a twin pregnancy?
AB  - OBJECTIVE: The objective was to determine whether small twins had a survival
      advantage with respect to small singletons after controlling for other factors
      associated with adverse perinatal outcome. STUDY DESIGN: A hospital-based cohort
      study included all births between 1980 and 1995 of babies born between 24 and 43
      weeks' gestation. Logistic regression was used to estimate the perinatal
      mortality risks for monochorionic and dichorionic twins with growth restriction
      after adjusting for gestational age, maternal age, parity, method of delivery,
      and the presence or absence of congenital malformations. RESULTS: The study
      sample included 1062 dichorionic twins, 354 monochorionic twins, and 59,873
      singletons. Small monochorionic and dichorionic twins showed a similar overall
      risk of perinatal mortality (odds ratio 1.40, confidence interval 0.86 to 2.25).
      However, monochorionic twins with birth weights <10th percentile faced an
      increased risk of perinatal death compared with singletons (odds ratio 2.45,
      confidence interval 1.20 to 5.02). Dichorionic twins had no such increased risk
      (odds ratio 0.91, confidence interval 0.45 to 1.84). CONCLUSIONS: Twins with
      growth restriction are not protected against perinatal loss, even after adjusting
      for congenital malformations. In fact, monochorionic twins are more than twice as
      likely to die in the perinatal period as are their singleton counterparts.

PMID- 9757969
TI  - The influence of obstetric no-fault compensation on obstetricians' practice
      patterns.
AB  - OBJECTIVES: The objectives were to determine level of satisfaction among
      obstetricians with the no-fault insurance programs in Florida and Virginia and to
      study any reported practice patterns attributable to implementation of no-fault
      compensation. STUDY DESIGN: Structured surveys were conducted with 119
      obstetricians in Florida and Virginia. RESULTS: More than 90% of obstetricians
      were enrolled in no-fault insurance programs, but only 13% reported having had a
      patient compensated by a no-fault program. Only 14% knew of a colleague with a
      patient who had been compensated. Despite no-fault compensation, threat of
      lawsuits was a factor in 39% of cases of physicians who quit practicing
      obstetrics. The no-fault programs did not cause obstetricians to report increases
      in their obstetric caseloads or in their fraction of patients at high risk.
      Overall, obstetricians were far more satisfied with the no-fault system than with
      the tort system. Still, more than half of the respondents expressed
      dissatisfaction with premiums assessed by no-fault insurance. CONCLUSION:
      Obstetricians who knew about the no-fault programs were generally satisfied with
      their performance. However, the no-fault programs have not built a constituency
      with physicians, and the programs are relatively small in their scope of
      coverage. No-fault compensation thus has had minor impact on reported obstetric
      practice. To be effective in improving patient access, no-fault compensation must
      be broader in scope.

PMID- 9757972
TI  - Limited usefulness of fetal weight in predicting neonatal brachial plexus injury.
AB  - OBJECTIVE: The objectives were to determine the neonatal morbidity rate from
      vaginal birth and examine fetal weight-based injury-prevention strategies. STUDY
      DESIGN: Selected neonatal morbidities were categorized by birth weight for all
      vertex vaginal deliveries occurring during a 12-year period. Sensitivity,
      specificity, and predictive values for brachial palsy were calculated at
      increasing birth weight cutoff levels. A policy of cesarean delivery for
      macrosomic infants was evaluated. RESULTS: There were 80 cases of brachial palsy
      among 63,761 infants (0.13%). In mothers without diabetes, rates in the 4500- to
      4999-g and >5000-g groups were 3.0% and 6.7%, respectively. A threshold of 3700 g
      had a sensitivity of 71% and a specificity of 86%; the positive predictive value
      was 0.56%. To prevent a single case of permanent injury, 155 to 588 cesarean
      deliveries are required at the currently recommended cutoff weight of 4500 g.
      CONCLUSIONS: The rates of lasting morbidity do not justify routine cesarean
      delivery for infants without diabetic complications weighing <5000 g.

PMID- 9757973
TI  - Persistent abnormalities in plasma volume and renal hemodynamics in patients with
      a history of preeclampsia.
AB  - OBJECTIVE: The objective was to test the hypothesis that women with a recent
      history of preeclampsia have abnormalities in renal hemodynamics and volume
      status. STUDY DESIGN: We studied a group of 26 primiparous women with history of
      preeclampsia and a group of 12 parous women with a history of uneventful
      pregnancies (control group). At least 4 months post partum we compared the
      following variables between these groups: effective renal plasma flow, glomerular
      filtration rate, plasma volume, plasma concentration of active renin, plasma
      concentration of angiotensin II, plasma concentration of aldosterone, and plasma
      concentration of atrial natriuretic peptide. RESULTS: Both plasma volume and
      plasma concentration of atrial natriuretic peptide were lower in the formerly
      preeclamptic group. Compared with the control subjects, the formerly preeclamptic
      group also had a lower effective renal plasma flow, a higher filtration fraction,
      and a higher renal vascular resistance. Intergroup differences in plasma
      concentration of active renin, plasma concentration of angiotensin II and plasma
      concentration of aldosterone were small and inconsistent. CONCLUSIONS: Women with
      history of preeclampsia are relatively hypovolemic and tend to have lower
      effective renal plasma flow and higher renal vascular resistance and filtration
      fraction than do control subjects. These findings support the hypothesis that
      otherwise healthy women with a history of preeclampsia show abnormalities in
      their volume status and renal hemodynamics, irrespective of their blood pressure.

PMID- 9757974
TI  - Fetal fibronectin as a marker to discriminate between ectopic and intrauterine
      pregnancies.
AB  - OBJECTIVE: Our purpose was to determine the accuracy of fetal fibronectin values
      for diagnosing ectopic pregnancies. STUDY DESIGN: We obtained vaginal swabs from
      women with pregnancies of < or = 12 weeks' gestation to perform enzyme-linked
      immunosorbent assays for fetal fibronectin. Fetal fibronectin values were
      compared among groups categorized on the basis of clinical and laboratory
      criteria into (1) ectopic pregnancies, (2) threatened abortions, (3)
      incomplete/complete abortions, and (4) uncomplicated intrauterine pregnancies.
      RESULTS: Mean fetal fibronectin values ranged from 0.08 microg/mL in women with
      ectopic pregnancies to 0.33 microg/mL in women with threatened abortions.
      Comparing these two diagnostic categories, a negative fetal fibronectin test (at
      a cutoff level of 0.300 microg/mL) predicted ectopic pregnancy with a sensitivity
      of 94%, specificity of 28%, positive predictive value of 62%, and negative
      predictive value of 78%. CONCLUSION: Although fetal fibronectin is low in women
      with ectopic pregnancies, a negative test is not sufficiently sensitive and
      specific to be used clinically for the diagnosis of ectopic pregnancy.

PMID- 9757975
TI  - The role of ultrasonography in the detection and management of adnexal masses
      during the second and third trimesters of pregnancy.
AB  - OBJECTIVE: Our purpose was to determine the effect of routine second-trimester
      and third-trimester ultrasonographic examinations on the prevalence of detectable
      and operable adnexal disease. STUDY DESIGN: The study group consisted of 7996
      pregnant women between 13.0 and 42.8 weeks' gestation. The size and architectural
      pattern of any detectable adnexal masses were noted. RESULTS: A total of 328 of
      the 7996 (4.1%) women in the study group had 335 ultrasonographically detectable
      adnexal masses; 309 of the masses were unilocular or had a single thin septation
      and 26 were architecturally complex. Of the ovarian cysts 252 of 309 (81.6%) had
      a mean diameter < 3.0 cm; 60% of the 252 patients in this subgroup had serial
      ultrasonographic examinations; 43 of the unilocular cysts resolved, and 17 have
      persisted for up to 2 years. There is a statistically significant trend toward
      decreasing frequency of ovarian cysts with increasing gestational age (chi2 for
      linear trend; P < .00001). Eighteen of the 7996 had an exploratory laparotomy (1
      operation per 444 deliveries) during pregnancy or in the postpartum period. In
      addition, 1 patient had a paratubal cyst excised at the time of postpartum
      bilateral tubal ligation. Pathologically confirmed lesions included 8 benign
      cystic teratomas, 3 mucinous cyst adenomas, 2 paratubal cysts, 2 corpus lutea, 1
      serous cystadenoma, 1 follicular cyst, 1 endometrioma, and 1 ovarian fibroma.
      CONCLUSION: Ovarian cysts are found in 4.1% of second-trimester and third
      trimester obstetric ultrasonographic examinations. Most ultrasonographically
      detectable cysts are < 3.0 cm in diameter and usually resolve. The frequency of
      exploratory laparotomy for adnexal disease is not significantly different from
      that in reports before the widespread use of obstetric ultrasonography.

PMID- 9757977
TI  - The safety of intraoperative autologous blood collection and autotransfusion
      during cesarean section.
AB  - OBJECTIVE: We evaluated the safety of intraoperative autologous blood collection
      and autotransfusion during cesarean section. STUDY DESIGN: A multicenter
      historical cohort study identified 139 patients in whom autologous blood
      collection autotransfusion during cesarean section was performed. We also
      identified 87 control patients who underwent similar surgical procedures at the
      same centers without autotransfusion. The outcome variables we compared were
      acute respiratory distress syndrome, amniotic fluid embolism, disseminated
      intravascular coagulation, need for ventilatory support, infectious morbidity,
      and the length of postpartum hospitalization. RESULTS: Demographic and obstetric
      characteristics were similar in both groups. The ranges of autotransfused volumes
      were 200 to 11,250 mL at Yale, 225 to 1160 mL at Good Samaritan, and 125 to 4750
      mL at Hinsdale. No statistically significant differences existed between the two
      groups in any of the outcome variables analyzed. No case of acute respiratory
      distress syndrome or amniotic fluid embolism was identified in either group.
      CONCLUSIONS: Our multicenter experience reveals no demonstrably increased risk of
      complications in patients receiving autologous blood collection autotransfusion
      during cesarean section.

PMID- 9757976
TI  - A "bloodless cesarean section" and perinatal transmission of the human
      immunodeficiency virus.
AB  - OBJECTIVE: Perinatal transmission of the human immunodeficiency virus is the main
      pathway for children to become infected with this virus; however, the relative
      contribution and timing of this transmission, whether transplacental or by
      exposure through the birth process, have not yet been elucidated. An obvious
      question is whether the mode of delivery has an impact on this transmission rate.
      However, a routine cesarean section will primarily diminish the duration of
      exposure of maternal bodily fluids to the neonate but does not prevent the baby
      from being exposed to maternal blood coming from the uterine incision. The
      purpose of this study was to determine whether the rate of perinatal transmission
      of human immunodeficiency virus could be significantly lowered by delivering the
      baby with minimal to no exposure to maternal blood or bodily fluids by the use of
      a surgical technique termed a "bloodless cesarean section." STUDY DESIGN: We
      performed a prospective cohort study in a group of pregnant women infected with
      human immunodeficiency virus and evaluated the rate of transmission of this virus
      to the neonate on the basis of the mode of delivery. One group of patients was
      delivered by means of a "bloodless cesarean section," in which the baby was
      delivered and not exposed to any maternal blood or bodily fluid. The control
      group gave birth either by vaginal delivery or by routine cesarean section. All
      of the newborns were followed up for a minimum of 15 months or until negative
      findings were confirmed. Multiple antenatal, intrapartum, and postdelivery
      variables were collected and analyzed. RESULTS: A total of 108 patients were
      included in this study and 14 neonates became infected with human
      immunodeficiency virus (13%). Three of 53 infants delivered by a bloodless
      cesarean section (5.7%) became infected compared with 11 of 55 control patients
      (20.0%). This was significant at P = .02 and represented an absolute difference
      in percentage between the 2 groups of 14.3%, which corresponds to a 71.5%
      relative reduction in transmission risk (z = 2.27, P = .012). Since the use of
      zidovudine greatly influences the perinatal transmission rate of human
      immunodeficiency virus, the study data were reanalyzed with the exclusion of
      patients who used antenatal or intrapartum zidovudine. Two of 32 infants in the
      bloodless cesarean section group (6.3%) were infected compared with 9 of 38 in
      the control group (23.7%). This was significant at P = .04 and revealed an
      absolute difference in percentage of 17.4%, which corresponds to a 73.4% relative
      reduction in transmission risk (z = 2.15, P = .016). There was no difference in
      the transmission rate between the bloodless cesarean section patients who did not
      use zidovudine (2/32, 6.3%) and the patients who did use zidovudine from the
      entire study population (3/38, 7.9%). CONCLUSION: In the absence of zidovudine
      usage, these data show that 70% to 75% of the perinatal transmission of human
      immunodeficiency virus to a newborn occurs from exposure to maternal blood and
      bodily fluids at the time of birth. This information is important for patients
      unable to take zidovudine or other antiretroviral agents, but more important, it
      introduces the concept of other treatment options for the future.

PMID- 9757978
TI  - The effects of nitric oxide on the contractility of isolated uterine and aortic
      rings from pregnant rats.
AB  - OBJECTIVE: The object was to compare the effects of nitric oxide on isolated
      uterus and aorta of pregnant rats. STUDY DESIGN: Rings of uterus and thoracic
      aorta without endothelium from Sprague-Dawley rats at mid and late gestation were
      used for isometric tension recording. The concentration-response curve for
      diethylamine/nitric oxide was studied in the presence or absence of oxyhemoglobin
      (10(-5) mol/L), or oxyhemoglobin was added after the response to
      diethylamine/nitric oxide. RESULTS: Diethylamine/nitric oxide concentration
      dependently inhibited uterine contractions, and the effect was attenuated by
      previous treatment with oxyhemoglobin at mid gestation (n = 8). The effects were
      negligible at late gestation (n = 8). The relaxation of aortic rings by
      diethylamine/nitric oxide and its attenuation by previous treatment with
      oxyhemoglobin were similar at mid (n = 6) and late (n = 6) gestation. The
      sensitivity of aortic rings to diethylamine/nitric oxide is significantly higher
      than that of uterine rings. Oxyhemoglobin partly restored inhibited
      diethylamine/nitric oxide phenylephrine tension in aortic rings and had no effect
      on diethylamine/nitric oxide-inhibited uterine rings. CONCLUSIONS: Uterine smooth
      muscle is less sensitive to nitric oxide than is aortic smooth muscle. Nitric
      oxide sensitivity of rat uterus but not aorta decreases toward term.

PMID- 9757980
TI  - Explicit memory in pregnant women.
AB  - OBJECTIVE: The study was conducted to systematically investigate previous
      anecdotal reports of memory decline during pregnancy. STUDY DESIGN: We used a
      longitudinal design to investigate memory in women throughout pregnancy and in
      the postpartum period. Closely matched, nonpregnant women were similarly studied
      at equivalent intervals. We also assessed degree of depression and anxiety.
      RESULTS: There was a significant time-by-group interaction (P < .01) for both
      immediate and delayed recall of paragraph length material. Contrasts showed a
      significant decline in memory for the pregnant group from the second to the third
      trimester (P < .01). No significant changes in memory were noted for the control
      group. The pregnant women scored higher on both depression and anxiety scales;
      however, somatic rather than cognitive items accounted for the elevated scores.
      Fluctuations in mood and memory did not coincide. CONCLUSION: There is a
      pregnancy-related decline in memory, which is limited to the third trimester. The
      decline is not attributable to depression, anxiety, sleep deprivation, or other
      physical changes associated with pregnancy.

PMID- 9757979
TI  - The safety of omeprazole during pregnancy: a multicenter prospective controlled
      study.
AB  - OBJECTIVES: Our purpose was to determine whether omeprazole use during pregnancy
      is associated with an increased risk of malformations, spontaneous abortions,
      decreased birth weight, or perinatal complications. STUDY DESIGN: In a
      multicenter, prospective controlled study, pregnant women exposed to omeprazole
      during gestation were matched with controls exposed to nonteratogens and with
      disease-paired controls who used histamine blockers for similar indications. The
      primary end point was the incidence of major malformations. RESULTS: One hundred
      thirteen pregnant women were exposed to omeprazole during pregnancy. Rates of
      major malformations in the omeprazole group (4%) did not differ from controls
      exposed to nonteratogens (2%) (P = .68, relative risk = 1.94, 95% confidence
      interval 0.36 to 10.36) and disease-paired controls (2.8%). Birth weight,
      gestational age at delivery, preterm deliveries, and neonatal complications were
      comparable among the three groups. CONCLUSIONS: No association was found between
      exposure to omeprazole during the period of organogenesis and increased risk for
      major malformations. Exposure throughout pregnancy is not associated with
      increased risk of spontaneous abortions, decreased birth weight, or perinatal
      complications.

PMID- 9757981
TI  - Midtrimester urine human chorionic gonadotropin beta-subunit core fragment levels
      and the subsequent development of pre-eclampsia.
AB  - OBJECTIVE: Our purpose was to determine whether midtrimester maternal urine human
      chorionic gonadotropin beta-subunit core fragment predicts later pre-eclampsia.
      STUDY DESIGN: Urine beta-core fragment levels standardized to spot creatinine
      concentration and expressed as multiples of the median were prospectively
      determined in 347 midtrimester singleton pregnancies undergoing genetic
      amniocentesis. All women considered in the analysis were white and nonsmokers.
      Obstetric chart review was undertaken after delivery to identify cases in which
      pre-eclampsia developed. The risk of pre-eclampsia at different threshold levels
      of beta-core fragment of human chorionic gonadotropin was determined. RESULTS:
      The median maternal age was 36.0 years, with a median gestational age at urine
      collection of 16.0 weeks. The median level of the beta-core fragment of human
      chorionic gonadotropin was 1385.5 ng/mg of creatinine in those with pre
      eclampsia, whereas that in those without pre-eclampsia was 1061.2 ng/mg. The
      difference was significant (Mann-Whitney U test, P = .03). A significant linear
      association was found between the beta-core fragment concentration and the risk
      of pre-eclampsia (Mantel-Haenszel test of linear association, P = .03). The
      relative risk and 95% confidence interval of subsequent pre-eclampsia increased
      from 2.07 (1.06 to 4.05) at beta-core fragment levels of human chorionic
      gonadotropin > or = 2.0 multiples of the median to 5.17 (1.95 to 13.7) at > or =
      4.0 multiples of the median. CONCLUSION: Clinically normal patients with elevated
      midtrimester levels of urine beta-core fragment of human chorionic gonadotropin
      are at increased risk for the subsequent development of pre-eclampsia. The
      clinical value of this urine analyte as a marker for pre-eclampsia needs to be
      further investigated.

PMID- 9757982
TI  - Outcomes of very low birth weight twins cared for in the National Institute of
      Child Health and Human Development Neonatal Research Network's intensive care
      units.
AB  - OBJECTIVE: The study's aim was to compare outcomes of very low birth weight twins
      with those of matched singletons. STUDY DESIGN: With data from the Neonatal
      Research Network registry (May 1991 to December 1994), univariable and
      multivariable comparisons of very low birth weight twin pairs and singletons were
      performed in 2 subgroups: (1) all paired twins and singletons with birth weights
      between 401 and 1500 g and (2) all paired twins and singletons born at <28 weeks'
      gestation. RESULTS: Twins constituted 19% of infants admitted with very low birth
      weight. Mothers of twins were more likely to receive prenatal care, have labor,
      have cesarean delivery, and receive antenatal glucocorticoids. Twins were more
      likely to have respiratory disease and to receive surfactant. Second-born twins
      had more early respiratory disease but similar longer-term outcomes. The risks of
      death, chronic lung disease, and grade III or IV intracranial hemorrhage were
      similar in twins and singletons. CONCLUSIONS: Although very low birth weight
      twins compose a sizable proportion of admissions, in National Institute of Child
      Health and Human Development Neonatal Research Network intensive care units,
      twins and singletons have similar outcomes.

PMID- 9757983
TI  - Evidence for mechanisms of the acute-phase response to endotoxin in late
      gestation fetal goats.
AB  - OBJECTIVE: The aim of this study was to evaluate the relationship between febrile
      response to fetal endotoxin administration and fetal plasma endogenous pyrogen,
      tumor necrosis factor-alpha, the possible putative pyrogen mediator prostaglandin
      E2, and the endogenous antipyretic arginine vasopressin in late-gestation
      pregnant goats. STUDY DESIGN: Changes in fetal core temperature, plasma tumor
      necrosis factor-alpha, prostaglandin E2, and arginine vasopressin levels were
      measured after administration of Escherichia coli endotoxin (70 microg/kg of
      fetal weight) to 10 fetal goats in late gestation. RESULTS: Fetal body
      temperature did not rise after endotoxin administration. Fetal plasma tumor
      necrosis factor-alpha and arginine vasopressin increased to 87.5 +/- 15.2 pg/mL
      and 25.1 +/- 4.8 pg/mL, respectively, after 1 to 2 hours (P < .05). Fetal plasma
      prostaglandin E2 levels did not change significantly throughout the study.
      CONCLUSION: The absence of a febrile response to endotoxin in late-gestation
      fetal goats is accompanied by a deficient responses in prostaglandin generation
      in the periphery and increased activity of the antipyrogen arginine vasopressin.

PMID- 9757984
TI  - Proton magnetic resonance spectroscopy of fetal lamb brain during hypoxia.
AB  - Proton magnetic resonance spectroscopy of fetal lamb brain was performed
      simultaneously with repeated measurements of fetal arterial oxygen saturation
      during decrease of oxygen supply. Magnetic resonance spectra displayed the same
      metabolite peaks as detected in the human fetal brain. Cerebral lactate signals
      could be detected during fetal hypoxia.

PMID- 9757985
TI  - Placental transfer of ritonavir with zidovudine in the ex vivo placental
      perfusion model.
AB  - OBJECTIVE: The object was to determine the placental transfer of ritonavir alone
      and in combination with zidovudine. STUDY DESIGN: Twelve placental perfusion
      studies were performed at trough (1-2 microg/mL) and peak (approximately 20
      microg/mL) combinations of ritonavir and zidovudine. Accumulation of ritonavir
      was determined. RESULTS: Transfer of ritonavir at trough concentrations was
      undetectable (<0.025 microg/mL). The clearance index of ritonavir at peak
      concentration was 0.085 +/- 0.05 and was unaffected by zidovudine. The fetal
      concentration of ritonavir was 0.0758 +/- 0.22 microg/mL at a maternal
      concentration of approximately 20 microg/mL and 25.5 +/- 6.9 microg/mL at a
      concentration of 100 microg/mL. There was no tissue accumulation of ritonavir
      either alone or with zidovudine. CONCLUSION: The clearance index of ritonavir at
      therapeutic levels was extremely low, with little accumulation in the fetal
      compartment and no accumulation in placental tissue. Zidovudine does not
      significantly affect the transfer or accumulation of ritonavir.

PMID- 9757986
TI  - Effects of fetal sex and race on risk of very preterm birth in twins.
AB  - OBJECTIVE: Our purpose was to determine whether the risk of twin preterm birth
      correlates with the number of male fetuses. STUDY DESIGN: Among 8109 white and
      1884 black twin pregnancies in the Missouri Successive Pregnancy Birth/Death Data
      Set, 1978 through 1990, risk for preterm birth at various gestational ages was
      determined with 0, 1, or 2 male infants. RESULTS: Studied as individuals, white
      preterm twins <35 weeks' gestation demonstrated a 9.2% excess of male fetuses (P
      < .001). Adjusted for monozygosity, risk for preterm birth <35 weeks' gestation
      was 15.7% in white female-female pairs, 17.9% in unlike-sex white fetuses, and
      20.2% in white male-male pairs (r = .999, P = .01). The effect was absent in
      black pregnancies and was unrelated to birth order, cesarean delivery, parity,
      twins' weight differential, year, or season. CONCLUSIONS: In white twin
      gestations the observed linear relationship between the number of male fetuses
      and the likelihood of preterm birth <35 weeks' gestation suggests a fetal
      mechanism for preterm birth <35 weeks' gestation linked to fetal sex. Studies of
      mechanisms for preterm birth must stratify by fetal sex and race.

PMID- 9757987
TI  - A randomized pilot trial of administration of granulocyte colony-stimulating
      factor to women before preterm delivery.
AB  - OBJECTIVE: The object was to determine whether administering recombinant human
      granulocyte colony-stimulating factor to women before a preterm delivery (< or =
      30 weeks' gestation) would improve fetal neutrophil production and neonatal
      outcome without adverse maternal effects. STUDY DESIGN: A single dose (25
      microg/kg) of recombinant human granulocyte colony-stimulating factor or placebo
      was given to 26 women in preterm labor in a randomized, double-blind study.
      Neutrophil production was assessed by marrow aspirations of neonates 24 hours
      after delivery, blood neutrophil counts were measured in neonates for 1 week, and
      Scores for Neonatal Acute Physiologic State were calculated on days 1 and 7 of
      life. RESULTS: Of the 26 women enrolled, 16 were delivered of 20 infants within 3
      weeks of receiving recombinant human granulocyte colony-stimulating factor. We
      found no apparent adverse effect on pregnancy duration or maternal comfort. The
      neonates born to mothers treated with recombinant human granulocyte colony
      stimulating factor had a significantly greater marrow proliferative pool (P < .05
      vs placebo) and a significant improvement in Scores for Neonatal Acute
      Physiologic State between days 1 and 7 (P < .02). CONCLUSIONS: Recombinant human
      granulocyte colony-stimulating factor administration to women before preterm
      delivery appears to have no significant immediate adverse effects on either the
      mother or the infant, and it could increase fetal neutrophil production and
      improve neonatal outcome.

PMID- 9757988
TI  - Maternal diabetes alters extracellular matrix protein levels in rat placentas.
AB  - OBJECTIVES: The aim of this study was to determine whether maternal diabetes
      affects placental levels of the extracellular matrix components fibronectin,
      laminin, and collagen-IV. STUDY DESIGN: Fibronectin, laminin, and collagen-IV
      deposition in term (day 20) rat placentas from normal and diabetic pregnancies
      was detected by use of Western blot, slot-blot, and immunohistochemical studies.
      RESULTS: Increased placental and decreased fetal wet weight were found in
      offspring of manifestly diabetic rats compared with offspring of normal
      pregnancies. Laminin deposition was reduced whereas fibronectin levels were
      increased in placentas from diabetic rats. No diabetes-induced changes of
      collagen-IV expression and deposition were found. CONCLUSION: The diabetes
      induced alterations of laminin and fibronectin protein levels in the fetal
      maternal interface may affect placental development and alter gas exchange and
      nutrient transfer to the offspring. This may in turn contribute to the abnormal
      fetal development in diabetic pregnancy.

PMID- 9757989
TI  - Population differences affect the interpretation of fetal nonstress test results.
AB  - OBJECTIVE: The object of the study was to determine whether population
      differences exist with respect to outcomes of women with reactive and nonreactive
      nonstress test results. STUDY DESIGN: An epidemiologic evaluation was conducted
      on 2579 women who underwent nonstress tests in the Fetal Assessment Center of the
      Johns Hopkins Hospital within a week of delivery. Risk factors such as
      hypertension, diabetes, and postterm pregnancy were used in a logistic regression
      model to evaluate the ability of the nonstress test to predict outcomes including
      proxies of fetal distress and fetal and neonatal death. The sensitivities,
      specificities, and predictive values of the nonstress test for predicting these
      outcomes in cohorts of black and white women were also determined. RESULTS: The
      nonstress test was consistently more sensitive for black women than for white
      women in predicting several perinatal outcomes, but specificity and negative
      predictive value were consistently lower for black women. The positive predictive
      value for fetal and neonatal death was higher for white women than for black
      women. Although the nonreactive nonstress test result seemed to be predictive of
      certain perinatal events, the odds ratio for predicting perinatal mortality in
      any study population was no greater than when the nonstress test result was
      reassuring. CONCLUSIONS: Epidemiologic characteristics affecting test results,
      such as disease prevalence and population differences, may lead to clinically
      significant differences in outcome prediction when these tests' results are used.
      These differences should be considered in the implementation of antepartum fetal
      testing programs.

PMID- 9757990
TI  - Immunoreactive adrenomedullin in human fetoplacental tissues.
AB  - OBJECTIVE: Adrenomedullin is increased in maternal plasma in pregnancy and has
      been found in very high concentrations in amniotic fluid and umbilical plasma. To
      identify adrenomedullin-producing tissue in pregnancy we measured adrenomedullin
      concentration and distribution in fetoplacental tissues. STUDY DESIGN: By use of
      a specific radioimmunoassay we determined the concentrations of adrenomedullin
      and, by immunohistochemical studies, its localization and distribution in fetal
      membranes and placentas collected at elective cesarean section from 11 healthy
      pregnant women at term. RESULTS: The content of adrenomedullin in placentas
      (117.7 +/- 7.8 pg/mg wet tissue) and fetal membranes (168.7 +/- 2.3 pg/mg wet
      tissue) was similar to the adrenomedullin concentration in adrenal medulla (157.3
      +/- 4.4 pg/mg wet tissue). Adrenomedullin staining appears to be greater in fetal
      membranes than in placentas and was localized in amnion and trophoblast cells. In
      term placentas positive staining was detected predominantly in extravillous
      trophoblast cells, although a few syncytiotrophoblast cells and endothelial cells
      of primary villi stained for adrenomedullin. CONCLUSION: This study provides
      evidence that is consistent with fetoplacental tissues as a site of synthesis or
      action of adrenomedullin during pregnancy.

PMID- 9757991
TI  - Abundant vascular anastomoses in monoamniotic versus diamniotic monochorionic
      placentas.
AB  - OBJECTIVE: The study's aim was to compare the vascular anatomy of monoamniotic
      with uncomplicated diamniotic monochorionic pregnancies. STUDY DESIGN: The
      fetoplacental circulations of both twins in 18 monochorionic placentas were
      perfused after delivery under optimal physiologic conditions, and anastomoses
      were delineated by dye-contrast injection. Six were from pregnancies with
      monochorionic monoamniotic twins and 12 from uncomplicated monochorionic
      diamniotic twin pregnancies. RESULTS: The cord insertions in monochorionic
      monoamniotic placentas were central, with a median intercord distance of 3.2 cm
      (range 1.7 to 6.9 cm), whereas in monochorionic diamniotic control placentas the
      cord insertions (n = 24) were rarely central (marginal, 13; velamentous, 2) or
      eccentric (6), with a mean intercord distance of 9.6 cm (5.2 to 16.7; P < .001).
      Cord entanglement was present in 5 of 6 cases of monochorionic monoamniotic
      placentas and in none of the monochorionic diamniotic placentas. Monochorionic
      monoamniotic placentas had more anastomoses than did monochorionic diamniotic
      placentas, both overall (median 13 vs 5 respectively, P < .01) and for each of
      the different types (arterioarterial, venovenous, and arteriovenous, P < .01).
      CONCLUSIONS: Monoamniotic monochorionic placentas have significantly greater
      numbers of both superficial and deep anastomoses than do uncomplicated
      monochorionic diamniotic pregnancies. This observation suggests a vascular basis
      for the extreme rarity of twin-twin transfusion syndrome in monoamniotic
      pregnancies.

PMID- 9757992
TI  - The effect of transforming growth factor and interleukin-10 on interleukin-8
      release by human amniochorion may regulate histologic chorioamnionitis.
AB  - OBJECTIVE: Amniochorion is a source of interleukin-8 during infection and
      inflammation. In this study we investigate the role of 2 immunoinhibitory
      cytokines, transforming growth factor and interleukin-10, in regulating
      interleukin-8 production from human fetal membranes and define their mechanism of
      regulation. STUDY DESIGN: Amniochorion was placed in an organ explant system for
      72 hours. Tissues were stimulated with lipopolysaccharide (50 ng/mL),
      lipopolysaccharide plus transforming growth factor-beta (50/50, 50/100),
      transforming growth factor-beta (50 and 100 ng/mL), lipopolysaccharide plus
      interleukin-10 (50/50 and 50/100), and interleukin-10 (50 and 100 ng/mL) in
      culture. Tissue and media samples were frozen until quantitation of interleukin-8
      messenger ribonucleic acid and protein. Quantitation of messenger ribonucleic
      acid was performed by quantitative competitive polymerase chain reaction and
      protein by enzyme-linked immunoassay, respectively. RESULTS: Lipopolysaccharide
      stimulated tissues produced approximately 6 x 10(6) molecules per microliter of
      interleukin-8 messenger ribonucleic acid compared with 6 x 10(3) molecules per
      microliter in controls. Transforming growth factor-beta alone and
      lipopolysaccharide plus transforming growth factor-beta stimulation produced 6 x
      10(5) and 6 x 10(4) molecules of interleukin-8 messenger ribonucleic acid per
      microliter, respectively. Tissues stimulated with lipopolysaccharide plus 50
      ng/mL interleukin-10 produced approximately 600 molecules per microliter of
      interleukin-8 messenger ribonucleic acid, whereas no amplifiable messenger
      ribonucleic acid was detected in tissues treated with lipopolysaccharide plus 100
      ng/mL interleukin-10. Tissues treated with interleukin-10 alone produced 6 x
      10(3) molecules of messenger ribonucleic acid, similar to control levels. Enzyme
      linked immunosorbent assay data showed similar levels of interleukin-8 peptide
      release from lipopolysaccharide and lipopolysaccharide plus transforming growth
      factor-beta-treated fetal membranes. A dose-dependent decrease in interleukin-8
      peptide release was seen in tissues treated with lipopolysaccharide plus
      interleukin-10, whereas stimulation with transforming growth factor or
      interleukin-10 alone resulted in interleukin-8 peptide release similar to that of
      control levels. CONCLUSION: Transforming growth factor-beta seems to have no
      effect on interleukin-8 protein production in the presence of an infectious
      agent; however, a drop in messenger ribonucleic acid levels was observed.
      Interleukin-10 in the presence of lipopolysaccharide showed down-regulation of
      interleukin-8 messenger ribonucleic acid expression and peptide production. These
      data suggest that fetal membrane interleukin-8 production can be controlled by
      interleukin-10 during an infectious process.

PMID- 9757993
TI  - Fetal blood sampling immediately before and within 24 hours of death in
      monochorionic twin pregnancies complicated by single intrauterine death.
AB  - OBJECTIVE: Our goal was to investigate the mechanisms that play a role in
      intrauterine death in monochorionic twins and that contribute to the high
      perinatal mortality and morbidity in the survivors. STUDY DESIGN: In 8
      monochorionic twin pregnancies complicated by the intrauterine death of a single
      twin, we took samples from 5 twin fetuses immediately before death and from 4 of
      their cotwins and also from 4 surviving fetuses within 24 hours after death of
      the cotwin. RESULTS: Four of the 5 fetuses sampled who subsequently died were
      acidemic and 3 were hypoxemic. None of these fetuses or their cotwins were anemic
      at that time. All 4 survivors sampled within 24 hours of the death of each cotwin
      had low hematocrits. CONCLUSION: Fetal anemia, probably the consequence of acute
      blood loss just before the time of death of the cotwin, may play a role in the
      high mortality and morbidity found in the surviving twin. It is unlikely that
      immediate delivery of the surviving twin after death could affect the outcome.

PMID- 9757994
TI  - The detection of diminished ovarian reserve in infertile women.
AB  - Women in their mid to late 30s and early 40s with infertility constitute the
      largest portion of the total infertility population. These women frequently
      undergo multiple testing, and most will require expensive and invasive therapies,
      including assisted reproductive technologies, with markedly reduced pregnancy
      rates in those older than 40. These women also have a higher incidence of
      pregnancy loss even after documentation of fetal cardiac activity by
      ultrasonography. Identifying those women who have a very low chance of pregnancy
      (and a high chance of pregnancy loss) with their own gametes presents a daily
      challenge to the practicing clinician, especially before embarking on expensive
      treatments. This article reviews the contemporary investigation of reproductive
      aging with basal and provocative tests. Women with markedly diminished ovarian
      reserve should be counseled on their low chances of conception with their own
      gametes, even with assisted reproductive technologies.

PMID- 9757995
TI  - Intravenous nitroglycerin in obstetrics: a new indication.
AB  - Intravenous nitroglycerin has been reported to be efficient in various emergency
      obstetric situations. We report here the first case of intravenous nitroglycerin
      use in a 20-week pregnant woman with abruptio placentae and hypertonia leading to
      in utero fetal death and difficult delivery.

PMID- 9757996
TI  - Aortic coarctation diagnosed after hypertension in pregnancy.
AB  - Coarctation of the aorta is an unusual cause of hypertension in pregnancy because
      the disorder in adults is often unrecognized by obstetricians or general
      practitioners managing antenatal clinics. We report 3 women with adult
      coarctation of the aorta that was diagnosed in the hypertension clinic after
      hypertensive pregnancies where the diagnosis had been missed.

PMID- 9757997
TI  - Benign schwannoma of the obturator nerve: a case report.
AB  - We describe a schwannoma of the obturator nerve in a woman 66 years old. It was
      diagnosed only postoperatively because of the aspecificity of the symptoms. The
      difficulty of making a correct diagnosis during surgery is discussed, and the
      potential serious consequences of total excision of the nerve are described.

PMID- 9757998
TI  - Papillary thyroid carcinoma manifesting as thyroid storm of pregnancy: case
      report.
AB  - A patient with known hyperthyroidism was seen at 25 weeks' gestation with a
      rapidly growing neck mass. She was initially in thyroid storm and received
      aggressive medical therapy. Two subsequent episodes of thyrotoxicosis occurred
      during pregnancy in spite of large doses of propylthiouracil. Post partum the
      patient was diagnosed with a locally advanced thyroid malignancy.

PMID- 9757999
TI  - Primary hepatoid carcinoma of ovary in pregnancy.
AB  - We report a rare case of a 35-year-old woman with primary hepatoid carcinoma of
      the ovary during pregnancy associated with abnormal levels of maternal serum
      alpha-fetoprotein. This tumor should be considered in the differential diagnosis
      of pregnant women with very high levels of maternal serum alpha-fetoprotein
      whenever other maternal or fetal sources are excluded.

PMID- 9758001
TI  - Hypoxic-ischemic fetal insult resulting from maternal aortic root replacement,
      with normal fetal heart rate at term.
AB  - A patient with Marfan's syndrome was seen at 29 weeks' gestation with acute
      aortic dissection. She underwent aortic root replacement under deep hypothermia
      and circulatory arrest. The fetal heart rate was ominous during surgery but
      recovered later. Serial ultrasonographic examinations showed progressive fetal
      brain atrophy. The patient was delivered at 38 weeks' gestation of a girl
      weighing 2305 g, in whom severe spastic tetraplegia, absent psychomotor
      development, and therapy-resistant epilepsy developed. This is the first case to
      document progressive fetal brain atrophy after cardiac surgery in pregnancy.

PMID- 9758000
TI  - Intrahepatic cholangiocarcinoma masquerading as the HELLP syndrome (hemolysis,
      elevated liver enzymes, and low platelet count) in pregnancy: case report.
AB  - A young woman was seen at 26 weeks' gestation with a clinical profile consistent
      with the HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet
      count). The patient underwent cesarean delivery and was found to have a massive
      tumor involving the liver. After correction of the coagulopathy, a liver biopsy
      specimen demonstrated an intrahepatic cholangiocarcinoma. The patient died 3
      weeks after diagnosis.

PMID- 9758002
TI  - The failed suppression of serum estradiol level by gonadotropin-releasing hormone
      agonist in a case of pelvic endometriosis.
AB  - We report a case in which gonadotropin-releasing hormone agonist for a patient
      with pelvic endometriosis did not suppress the endometrial growth or serum levels
      of estradiol or follicle-stimulating hormone but did that of luteinizing hormone,
      regardless of the therapeutic dose in blood.

PMID- 9758003
TI  - Uterine leiomyoma as a rare cause of acute abdomen and intestinal gangrene.
AB  - A rare case of mesenteric vein thrombosis and small intestinal gangrene caused by
      a pedunculated fundal uterine fibroid is presented. The causative mechanism and
      management are discussed.

PMID- 9758004
TI  - Brachial artery rupture complicating a pregnancy with neurofibromatosis: a case
      report.
AB  - A 30-year-old black woman was first seen at 34 weeks' gestation with pain in the
      right arm, which was already afflicted with neurofibroma. She was in hypovolemic
      shock on presentation, and after she was resuscitated, a live infant was
      delivered. The patient was diagnosed with a pseudoaneurysm of the right brachial
      artery with extravasation of blood in the interstitium of the arm. Although there
      have been other reported cases of arterial rupture in pregnancies with
      neurofibromatosis, the report of brachial artery rupture in this situation is
      believed to be the first documented case.

PMID- 9758005
TI  - Fetal growth restriction induced by cortisone 40 years ago.

PMID- 9758006
TI  - Recurrent spontaneous ovarian hyperstimulation syndrome.

PMID- 9758007
TI  - Comments on the quality of citations in journals.

PMID- 9758008
TI  - Diurnal rhythms of labor and delivery.

PMID- 9758009
TI  - More (and less) on shoulder dystocia.

PMID- 9758010
TI  - Is it polycystic ovary syndrome causing the hyperstimulation again?

PMID- 9758011
TI  - The social ecology of drug use: a factor analysis of an urban environment.
AB  - Drug use is related to the environment in which drug users live. Using 32
      economic, housing, crime, and health variables for 1990 census tracts in Houston,
      Texas, this study found four identifiable factors: social disorganization,
      economic success, threat of violence, and chronic disease. Narcotic offenses
      loaded strongly on one and weakly on two of the factors; this variable did not
      load on the economic success factor. These results suggest that a textured look
      at drug use environments finds them to be multidimensional. Urban dwellers must
      deal with the independent effects of social disorganization, economic conditions,
      chronic disease, and violence.

PMID- 9758012
TI  - Stressful life events and adolescent substance use and depression: conditional
      and gender differentiated effects.
AB  - Stressful life circumstances have myriad influences on human health and behavior.
      Early research focused on the variable distribution of stress and its effects by
      socioeconomic status, race, and gender. More recent research indicates that
      variation by age is also an important consideration. For example, adolescent
      reactions to stressful life events are often inconsistent with adult reactions to
      similar life situations and transitions. Moreover, since most studies assess only
      a single outcome--usually depression--they risk classification bias since
      analyses exclude other potential stress-related outcomes. This paper assesses the
      gender distinct effects of stressful life events on two outcomes among
      adolescents, substance use and depressive symptoms. The results of a second-order
      regression model indicate that life events affect female, but not male,
      depressive symptoms, especially when self-esteem is low or mastery is high.
      Furthermore, life events affect substance use when peer drug use is high, or when
      parental support is low, but this latter effect is limited to female adolescents.

PMID- 9758013
TI  - Drug identity change processes, race, and gender. I. Explanations of drug misuse
      and a new identity-based model.
AB  - The present paper explores race and gender differences in a recent theoretical
      model (Anderson, 1994), consisting of several micro- and macrofactors, that helps
      explain the identity-related processes of drug misuse. The approach is
      qualitative, featuring in-depth interviewing with 45 self-identified drug
      addicts. The study uncovered support for the general concepts of the identity
      based model across four subgroups: Black females, White females, Black males, and
      White males. However, important race and gender differences emerged. Gender and
      race-related socialization and stratification explain most of the differences and
      suggest reconceptualization of the model. The investigation further demonstrates
      the promise of identity-based approaches in extending our knowledge of the
      etiology of drug misuse and related intervention policies.

PMID- 9758014
TI  - Interaction effects of client and treatment program characteristics on retention:
      an exploratory analysis using hierarchical linear models.
AB  - This paper applied a hierarchical linear modeling approach to explore the
      interaction effects of treatment program and client characteristics on client
      retention in treatment for drug users. Program characteristics included services
      provision, funding sources, and staff-client gender congruence, and client
      characteristics included gender, age at admission, and drug use level prior to
      admission. The same model was applied separately to three modalities:
      residential, methadone maintenance, and outpatient drug-free programs. Data were
      obtained from 59 treatment programs and 3,764 of their clients who had discharge
      records. The most noteworthy significant interaction effect detected was
      program's funding source and client's gender on treatment retention in the
      outpatient drug-free modality. For example, female clients remained less time in
      the programs that accepted only public funding than in the programs that accepted
      both public and private funding. Male clients remained in the treatment an
      average of 25.3 fewer days than female clients in drug-free programs that only
      accepted public fund, but stayed about the same time as females if the programs
      received mixed funding.

PMID- 9758015
TI  - Short- and long-term effects of a pilot prevention program to reduce alcohol
      consumption.
AB  - This study examined the effects of a brief, pilot alcohol prevention intervention
      for 211 disadvantaged 6th grade school children at posttest and 1-year follow-up.
      Process data indicated that the intervention was successfully implemented and
      well received by youth and parent/guardian participants. ANCOVA analyses
      indicated a significant difference on alcohol use frequency for drinking subjects
      at 1-month posttest, with less frequent use reported by intervention subjects
      than subjects receiving the minimal control materials, F(1,22) = 5.37, p = .03.
      No differences were found between intervention and control subjects on alcohol
      use measures at 1-year follow-up. Critical issues to be resolved related to the
      success of future prevention research and practice are discussed.

PMID- 9758017
TI  - Comments on "The moral economies of homeless heroin addicts: confronting
      ethnography, HIV risk, and everyday violence in San Francisco shooting
      encampments," by Phillippe Bourgois.

PMID- 9758016
TI  - The moral economies of homeless heroin addicts: confronting ethnography, HIV
      risk, and everyday violence in San Francisco shooting encampments.
AB  - Ethnographic immersion among homeless heroin addicts in San Francisco documents
      far more risky practices than the public health literature routinely reports. The
      logics of street-based income-generating strategies and the moral economy of
      social networking among self-identified "dope fiends" results in almost daily
      shares of drug preparation paraphernalia. Public health researchers need to
      reconceptualize their psychological behaviorist paradigm of "individual health
      risk behavior" because the pragmatics of income-generating strategies and the
      social symbolic hierarchies of respect, identity, and mutual dependence shape
      risky behavior. The explanatory potentials and the applied interventions that
      participant-observation anthropological approaches could bring to epidemiological
      public health research have not been utilized effectively in the field of HIV
      prevention and substance use. The accuracy of quantitative public health
      databases and our understanding of the who/why/how/where of HIV infection could
      be improved by a cross-methodological dialogue with participant-observation
      fieldworkers and by a greater theoretical sophistication with respect to power,
      violence, and extreme social marginalization.

PMID- 9758018
TI  - Comments on "The moral economies of homeless heroin addicts: confronting
      ethnography, HIV risk, and everyday violence in San Francisco shooting
      encampments," by Phillippe Bourgois.

PMID- 9758019
TI  - Comments on "The moral economies of homeless heroin addicts: confronting
      ethnography, HIV risk, and everyday violence in San Francisco shooting
      encampments," by Phillippe Bourgois.

PMID- 9758020
TI  - Comments on "The moral economies of homeless heroin addicts: confronting
      ethnography, HIV risk, and everyday violence in San Francisco shooting
      encampments," by Phillippe Bourgois.

PMID- 9758021
TI  - Comments on "The moral economies of homeless heroin addicts: confronting
      ethnography, HIV risk, and everyday violence in San Francisco shooting
      encampments," by Phillippe Bourgois.

PMID- 9758022
TI  - Comments on "The moral economies of homeless heroin addicts: confronting
      ethnography, HIV risk, and everyday violence in San Francisco shooting
      encampments," by Phillippe Bourgois.

PMID- 9758023
TI  - The metabolic fate of long-term inhaled nitric oxide.
AB  - PURPOSE: The fate of inhaled nitric oxide (NO) has not been precisely defined in
      critically ill patients. This study aimed at defining the effects of long-term NO
      inhalation on circulating NO byproduct levels. MATERIAL AND METHODS: During NO
      therapy, plasma and urine from 13 critically ill patients were sampled daily for
      determination of the stable byproducts of NO (nitrite [NO2-] and nitrate [NO3-].
      Routine monitoring data included inhaled NO concentration, hemodynamic
      parameters, arterial blood gases, creatinine clearance, and C-reactive protein.
      RESULTS: For the first 24 hours of NO inhalation (6.3+/-1.1 ppm), NO3- plasma
      concentration increased (from 13.3+/-5.4 to 52.3+/-17.6 micromol/L), but NO2-
      plasma concentration was not affected. The NO3- plasma concentration was
      correlated with the C-reactive protein level, the inhaled NO concentration. Renal
      excretion of NO metabolites was unaltered by NO inhalation. The NO3
      concentrations returned to baseline when NO therapy was discontinued. CONCLUSION:
      Long-term NO inhalation was associated with a consistent increase in the NO3-
      plasma concentration. NO byproducts may be implicated in the systemic effects
      associated with this treatment.

PMID- 9758024
TI  - Cerebral blood flow is proportional to cardiac index in patients with septic
      shock.
AB  - PURPOSE: In patients with septic shock, the cardiac index is often increased.
      Maldistribution of blood flow and regional hypoperfusion has been implicated as a
      key factor in the pathogenesis of organ dysfunction in these patients. We have
      investigated the relationship between cerebral blood flow and cardiac index in
      patients with septic shock. MATERIALS AND METHODS: We used Doppler ultrasound
      techniques to investigate limb and carotid blood flow in 15 patients with septic
      shock and 9 nonseptic controls. RESULTS: In the nonseptic control patients,
      common femoral and brachial blood flow were proportional to cardiac index (r=0.73
      and 0.76; P=.038 and .017, respectively) reflecting a protective redistribution
      of flow to more vital organs. However, this relationship was absent in patients
      with septic shock (r=0.23 and 0.21). Furthermore, in the septic patients but not
      the nonseptic controls, cerebral blood flow was correlated with the cardiac index
      (r=0.66, P < .05 vs r=-0.36, NS in nonseptic controls). Carotid flow was
      independent of mean arterial pressure, PaCO2 and PaO2 in patients with septic
      shock. CONCLUSIONS: These data are consistent with a loss of autoregulation of
      cerebral blood flow and a change in the control of limb blood flow in humans with
      septic shock.

PMID- 9758025
TI  - Optimal pressure support level for beginning weaning in patients with COPD:
      measurement of diaphragmatic activity with step-by-step decreasing pressure
      support level.
AB  - PURPOSE: The study objective was to determine an "optimal" individual pressure
      support (PS) level for beginning weaning with PS ventilation in patients with
      chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: Eleven COPD
      patients intubated and ventilated for acute respiratory failure and judged ready
      for weaning were studied. The technique consisted of lowering the PS level from a
      point that was characteristic for each patient and measurable under controlled
      mechanical ventilation, after setting the ventilator as recommended for COPD
      patients judged ready for weaning, that is, peak inflation pressure (PIP). This
      determination was based mainly on exploring the diaphragm with an
      electromyographic technique by defining the optimal PS level as the lowest PS
      level associated with no EMG evidence of diaphragmatic stress. Diaphragmatic
      electromyographic activity (diEMG) was recorded by a bipolar esophageal electrode
      (Disa-Denmark), and the high-frequency electrical component/low-frequency ratio
      (H/L) was calculated. The reference H/L was determined during a few spontaneous
      ventilatory cycles. Muscle stress was defined as a greater than 20% reduction in
      H/L compared with the reference value. RESULTS: Optimal PS levels ranged from 4
      to 24 cm H2O with a mean of 14+/-6 cm H2O. Two patients with optimal PS level at
      4 cm H2O did not require weaning and were quickly extubated. For the nine other
      patients, optimal PS levels were found to be 70% of PIP; in none was it necessary
      during weaning to use PS levels higher than individual optimal PS levels.
      CONCLUSIONS: Optimal PS level established with diEMG monitoring seems to be a
      useful index for beginning weaning in the PS ventilation mode in COPD patients.
      The hypothesis of beginning weaning with a PS level equal to 70% of PIP needs to
      be tested.

PMID- 9758026
TI  - Effect of continuous lateral rotational therapy on lung mucus transport in
      mechanically ventilated patients.
AB  - PURPOSE: Continuous lateral rotational therapy (CLRT) <40 degrees is a method of
      altering the position of the ventilated patient to help clear secretions from the
      lung. CLRT has not been shown to reduce the incidence of atelectasis or pneumonia
      but potentially offers a way to maximize positional drainage in these patients
      without producing adverse effects. Treatment intervention, bracketed by two
      (nonrotational) control periods. The purpose of this study was to determine if
      CLRT alters mucus transport in critically ill, intubated patients in the
      intensive care unit of a teaching hospital. MATERIALS AND METHODS: Thirteen
      critically ill, but stable, mechanically ventilated patients, mean age 74 years,
      were enrolled. They were placed supine on a Biodyne bed (KCI, San Antonio, Texas)
      and pressures in the cushions adjusted to patient's weight. A radiolabeled
      aerosol was delivered by bagging for 2 to 3 minutes and repeated measurements of
      lung radioactivity were obtained by imaging of the thorax over the following 3
      hours. A 90-minute period of rotation of the bed, 30 degrees to either side was
      preceded and followed by two 45-minute control periods during which the patient
      remained supine and stationary on the bed. Coughs and suctions were recorded and
      blood gases obtained pre and post study. RESULTS: (1) The mucous clearance was
      slower than that reported in normal subjects and in ambulatory patients with
      COPD; (2) there was a slight, but not significant, increase in clearance during
      CLRT; (3) clearance reverted to pre-oscillation levels following therapy. Lack of
      significant effect may be attributed to too shallow an angle for rotation or too
      short an intervention period. CONCLUSION: Positional drainage effected by short
      duration CLRT did not appear to stimulate significant mucous removal from the
      lung in critically ill patients but also did not cause any adverse effects.

PMID- 9758027
TI  - Volume recruitment and oxygenation in pulmonary edema: a comparison between HFOV
      and CMV.
AB  - PURPOSE: In acute lung injury, edema floods alveoli decreasing mean lung volume
      (MLV) and increasing pulmonary venous admixture (Ova/Qt). We reasoned that a
      ventilatory strategy that uses large tidal volumes (VT) might recruit volume
      differently than a strategy that uses very small VT (high-frequency oscillatory
      ventilation, HFOV) which may require an inflation maneuver to total lung capacity
      (TLC) for full recruitment. MATERIALS AND METHODS: We studied six dogs with
      pulmonary edema induced by oleic acid injury and compared HFOV with conventional
      mechanical ventilation (CMV). Increasing mean airway opening pressure (Pao) from
      6 to 14 cm H2O raised MLV from 932+/-162 to 1,550+/-210 mL and from 872+/-145 to
      1,242+/-192 mL during CMV and HFOV, respectively, whereas Qva/Qt decreased from
      24.1+/-8.5 to 9.3+/-4.3% and from 42.2+/-6.8 to 30.4+/-9.3%. We repeated our
      measurements at a Pao of 14 cm H2O after an inflation maneuver to TLC. RESULTS:
      Intlation to TLC recruited additional lung volume and decreased Qva/Qt further
      only during HFOV. After an inflation to TLC, we observed a rapid isobaric volume
      loss from the deflation limb of the pressure-volume curve during both CMV and
      HFOV. CONCLUSIONS: We conclude that after oleic acid injury in dogs pressure
      volume hysteresis has two components: a recruitable portion associated with gas
      exchange improvement and a nonrecruitable portion. At the level of PEEP used in
      this study (8.5 cm H2O), full lung recruitment during HFOV required inflation to
      TLC, whereas during CMV it was accomplished by the relatively large VT.

PMID- 9758028
TI  - Partial liquid ventilation decreases albumin leak in the setting of acute lung
      injury.
AB  - PURPOSE: This study evaluated the ability of partial liquid ventilation (PLV, gas
      ventilation of the perfluorocarbon-filled lungs) to reduce the amount of lung
      albumin leak present in the setting of acute lung injury. MATERIALS AND METHODS:
      An experimental controlled, randomized design was used. All studies were
      performed in the liquid ventilation laboratories at the University of Michigan
      Medical Center. Twenty-five Sprague-Dawley male rats 500+/-50 g were divided into
      five experimental groups: (1) CVF only (n=5), animals were cobra venom factor
      (CVF) lung injured; (2) PLV-CVF (n=5) animals received perflubron and PLV before
      CVF lung injury; (3) CVF-PLV (n=5) animals received PLV after CVF lung injury;
      (4) PLV only (n=5) animals underwent partial liquid ventilation without lung
      injury; and (5) Gas only (n=5) animals underwent gas ventilation without lung
      injury. In all groups iodinated bovine serum albumin (125I-BSA) was delivered by
      intravenous injection along with CVF or a saline placebo. RESULTS: When the CVF
      animals were compared with all other groups, a decrease in albumin leak was
      observed for all groups when compared with the CVF only controls (P < .001 by
      ANOVA; CVF only=1.22+/-0.12 versus PLV-CVF=0.46+/-0.08, P < .001; CVF-PLV=0.70+/
      0.25, P < .001; PLV only=0.22+/-0.01, P < .001; Gas only=0.17+/-0.02, P < .001).
      CONCLUSIONS: These data suggest that intratracheal instillation of
      perfluorocarbon before or after induction of lung injury results in a reduction
      in pulmonary albumin leak.

PMID- 9758029
TI  - Surrogates' agreement with patients' resuscitation preferences: effect of age,
      relationship, and SUPPORT intervention. Study to Understand Prognoses and
      Preferences for Outcomes and Risks of Treatment.
AB  - PURPOSE: The purpose of this study was to evaluate an intervention to improve
      patient-surrogate agreement on end-of-life resuscitation preferences. MATERIALS
      AND METHODS: Seven hundred seventeen patients with a 50% 6-month survival rate
      and their surrogate decision-makers were recruited for a randomized clinical
      trial from five teaching hospitals participating in the Study to Understand
      Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT).
      Intervention patients (n=386) were assigned specially trained nurses who spent
      extra time with patients and families explaining prognoses and treatments.
      Control patients (n=331) received usual care. Patient preferences and surrogate's
      perception of those preferences at pre- and post-intervention interviews were
      compared. RESULTS: Agreement between patients and surrogates was 75.0% at the day
      3 interview and 79.6% at the month 2 interview, increasing 4.6% (95% CI: 0.1%,
      9.1%). Improvements in agreement from day 3 to month 2 were seen equally in both
      study groups. A multivariable analysis verified that the intervention did not
      have an effect on agreement and indicated a decrease in agreement among older
      patients and among surrogates not in the immediate family. CONCLUSIONS: The
      SUPPORT intervention was not successful in increasing agreement between patients
      and surrogates. Because of the complex issues involved in end-of-life decision
      making, a more aggressive intervention may be needed. Other findings suggest that
      improvements in communication are particularly needed when patients are older and
      when the surrogate is not a patient's immediate relative.

PMID- 9758030
TI  - Thoracocardiography: noninvasive monitoring of left ventricular stroke volume.
AB  - PURPOSE: Thoracocardiography noninvasively monitors global stroke volume by
      inductive plethysmographic recording of ventricular volume curves as previously
      validated by thermodilution. Our purpose was to investigate the potential of
      thoracocardiography to individually assess stroke volume of the left ventricle.
      We hypothesized that curves predominantly reflecting left ventricular volume
      could be obtained by recording waveforms from thoracocardiographic transducers
      placed at various levels around the chest, and by identifying their origin as the
      left ventricle if mean expiratory exceeded mean inspiratory stroke volumes during
      spontaneous breathing. MATERIALS AND METHODS: Stroke volumes obtained by
      thoracocardiography in normal subjects were compared beat by beat with estimates
      derived from simultaneous measurements of left ventricular cavity stroke area by
      echocardiography with automatic boundary detection. Changes in respiratory
      variations of stroke volumes were analyzed during spontaneous breathing at fixed
      rate and tidal volume, during mechanical ventilation, and resistive loaded
      breathing. RESULTS: In 170 comparisons of beat-by-beat stroke volumes, 89% of
      thoracocardiographic fell within +/-20% of echocardiographic estimates. Changes
      in tidal volume, resistive loaded breathing, and mechanical ventilation induced
      respiratory variations of thoracocardiographic derived stroke volumes consistent
      with the known effect of respiratory changes in intrapleural pressure on left
      ventricular stroke volumes. CONCLUSIONS: The results suggest that
      thoracocardiography noninvasively tracks changes in left ventricular stroke
      volumes. Their absolute value may also be monitored if an initial calibration by
      an independent technique, such as echocardiography, is performed.

PMID- 9758031
TI  - Equilibrium vapour pressure of mercury from dental amalgam under loading
      conditions.
AB  - Earlier studies have failed to establish a consensus on the amount of mercury
      vapour released from dental amalgam restorations. The purpose of this study was
      to accurately and quantitatively measure the equilibrium mercury vapour pressure
      from dental amalgam. The vapour pressure was measured using a quartz crystal
      microbalance as a function of the load from 0-5.4 MPa. Auger spectra were
      collected of the as-formed and argon ion sputter cleaned dental amalgam surface.
      For the as-formed surface the mercury vapour density is zero with no load and
      increases to 0.6 microg m(-3) at 5.4 M Pa. Following cleaning the mercury, vapour
      density increased to a maximum value of 15 microg m(-3). The Auger spectra of the
      as-formed surfaces were dominated by features associated with carbon and oxygen.
      These spectral results in concert with the mercury vapour density measurements
      indicate that the oxide film on the as-formed surfaces inhibited the release of
      mercury vapour. The results of this experiment provide an upper limit for the
      amount of mercury vapour released by dental amalgams. Under conditions simulating
      the oral cavity this value would be reduced by oxides that form on the surface of
      dental amalgam restorations.

PMID- 9758032
TI  - In vivo osteogenesis assay: a rapid method for quantitative analysis.
AB  - A quantitative in vivo osteogenesis assay is a useful tool for the analysis of
      cells and bioactive factors that affect the amount or rate of bone formation.
      There are currently two assays in general use for the in vivo assessment of
      osteogenesis by isolated cells: diffusion chambers and porous calcium phosphate
      ceramics. Due to the relative ease of specimen preparation and reproducibility of
      results, the porous ceramic assay was chosen for the development of a rapid
      method for quantitating in vivo bone formation. The ceramic cube implantation
      technique consists of combining osteogenic cells with 27-mm3 porous calcium
      phosphate ceramics, implanting the cell-ceramic composites subcutaneously into an
      immuno-tolerant host, and, after 2-6 weeks, harvesting and preparing the ceramic
      implants for histologic analysis. A drawback to the analysis of bone formation
      within these porous ceramics is that the entire cube must be examined to find
      small foci of bone present in some samples; a single cross-sectional area is not
      representative. For this reason, image analysis of serial sections from ceramics
      is often prohibitively time-consuming. Two alternative scoring methodologies were
      tested and compared to bone volume measurements obtained by image analysis. The
      two subjective scoring methods were: (1) Bone Scale: the amount of bone within
      pores of the ceramic implant is estimated on a scale of 0-4 based on the degree
      of bone fill (0=no bone, 1=up to 25%, 2=25 to 75%, 4=75 to 100% fill); and (2)
      Percentage Bone: the amount of bone is estimated by determining the percentage of
      ceramic pores which contain bone. Every tenth section of serially sectioned cubes
      was scored by each of these methods under double-blind conditions, and the Bone
      Scale and Percentage Bone results were directly compared to image analysis
      measurements from identical samples. Correlation coefficients indicate that the
      Percentage Bone method was more accurate than the Bone Scale scoring method. The
      Bone Scale scoring method gave an r2=0.767 while the Percentage Bone method gave
      a value of 0.902. These results indicate that scoring ceramic cubes by the
      percentage of pores containing bone gives a result that corresponds to image
      analysis measurements at nearly a 90% confidence level. Thus, the Percentage Bone
      method of scoring is an accurate and relatively quick scoring method for in vivo
      bone formation.

PMID- 9758033
TI  - Composite technology in load-bearing orthopaedic implants.
AB  - Composite materials have been widely promoted as possible orthopaedic
      biomaterials but to date have found few successful commercial applications, due
      to the many challenging problems presented by their design, fabrication and
      testing. The range of possible composite biomaterials is reviewed, together with
      the possible methods of fabrication and the limitations that these place on the
      design of composite components. The use of composite materials allows many new
      design possibilities, but this freedom of design requires a clearer understanding
      of the objectives and constraints on the design process. The testing of composite
      components also presents many challenging problems, which are not adequately
      addressed by existing standards developed for testing conventional monolithic
      materials. The interaction of composite materials with the body is more complex
      than that of the component materials, and the prediction of their long-term
      mechanical performance also presents many intractable difficulties. However,
      despite these challenges composite materials are likely to prove invaluable in
      the future development of orthopaedics.

PMID- 9758034
TI  - Light-induced tailoring of PEG-hydrogel properties.
AB  - We have previously reported (Andreopoulos et al. J Am Chem Soc 118 (1996) 6235
      6240) the synthesis of hydrogels via the photopolymerization of water-soluble PEG
      molecules. In this paper, PEG-hydrogel membranes were prepared by the irradiation
      (> 300 nm) of aqueous solutions of photosensitive 4-armed PEG (nominal molecular
      weight of 20000), in the absence of photo-initiators. The hydroxyl termini of the
      PEG's were functionalized with cinnamylidene acetate groups to form
      photosensitive PEG macromers (PEG-CA), which upon irradiation (>300 nm) formed
      crosslinks between adjacent cinnamylidene groups resulting in highly crosslinked
      networks (hydrogels) (Andreopoulos et al. J Am Chem Soc 118 (1996) 6235-6240).
      The hydrogel membranes were highly swellable with equilibrium volume fractions
      ranging from 0.02 to 0.05. Their swellability was a function of irradiation light
      (>300 nm) and degree of modification of the PEG molecules. The effect of light on
      the permeation fluxes of myoglobin (Mb), hemoglobin (Hb), and lactate
      dehydrogenase-L (LDH) through PEG membranes was also assessed and the diffusion
      coefficients of the proteins were determined accordingly. The PEG-CA membranes
      exhibited photoscissive behavior upon exposure to UV irradiation (254 nm).
      Therefore, UV light was used as a trigger to control the mesh size of the
      membranes, and thereby the permeation fluxes of Mb, Hb, and LDH. Equilibrium
      swelling experiments with membranes prepared under different irradiation
      conditions were performed, and the Flory-Huggins model was utilized to determine
      the mesh size and the average molecular weight between crosslinks of the
      synthesized hydrogels.

PMID- 9758035
TI  - The use of SIMS, XPS and in situ AFM to probe the acid catalysed hydrolysis of
      poly(orthoesters).
AB  - Due to poly(orthoesters) being susceptible to acid catalysed hydrolysis, these
      polymers have attracted considerable interest for the controlled delivery of
      therapeutic agents within biodegradable matrices. The pH-sensitivity of the poly
      (orthoesters) has lead to several drug delivery systems being developed, whose
      rate of drug release is predominantly controlled by the rate of polymer
      hydrolysis. This study reports on the use of X-ray photoelectron spectroscopy
      (XPS), secondary ion mass spectrometry (SIMS), and atomic force microscopy (AFM)
      in a multitechnique approach to probe the effect of acid catalysed hydrolysis at
      the interface of poly(orthoesters). The molecular specificity of SIMS was
      successfully employed, suggesting that the preferred mechanism for hydrolysis was
      via the cleavage of an exocyclic alkoxy bond in the 3,9,-diethylidene-2,4,8,10
      tetraoxaspiro [5,5] undecane(DETOSU) unit. The resulting change in the surface
      chemical structure of the partially hydrolysed poly(orthoester) is such that it
      was not detectable by XPS analysis. Images acquired from an in situ AFM study of
      the hydrolysis ofa poly(orthoester), showed changes in the surface morphology,
      seen as the formation of pits, and an overall thinning of the polymer film. The
      use of SIMS, XPS and AFM has enabled changes in surface chemistry to be compared
      with changes in surface morphology. These complementary data, on the behaviour of
      the polymer during degradation have important implications for the further design
      of novel biodegradable materials.

PMID- 9758036
TI  - A hydrophobic interaction site for lysozyme binding to polyethylene glycol and
      model contact lens polymers.
AB  - Proton nuclear magnetic resonance (1H-NMR) spectroscopy is used to identify a
      preferred binding site for uncharged hydrophilic polymers on the surface of hen
      egg-white lysozyme. Chemical shift titrations show that exchangeable proton
      signals from amino acids Arg-61, Trp-62, Trp-63, Arg-73, Lys-96 and Asp-101 are
      selectively perturbed upon binding of poly(ethylene oxide), poly(ethylene glycol)
      and poly(ethylene-co-propylene oxide). The greatest binding-induced chemical
      shift changes are observed for Trp-62, Arg-61 and Arg-73 at the edge of the
      active site cleft of the protein, consistent with a predominantly hydrophobic
      interaction mode involving the polymer ethylene moieties. The more hydrophilic
      species poly(dihydroxypropyl methacrylate) causes similar but substantially
      smaller chemical shift effects than the other polymers, confirming the nature of
      the interaction. A dissociation constant of 76+/-5 mM is determined for the
      poly(ethylene glycol)-lysozyme complex. The relatively low affinity of the
      protein-polymer interactions compared to oligosaccharide substrate binding
      suggests that lysozyme activity is minimally affected by these materials.

PMID- 9758037
TI  - In vivo UHMWPE biodegradation of retrieved prosthesis.
AB  - Sixty-two ultra high molecular weight polyethylene prosthetic components (PEs)
      (31 tibial plateaux and 31 cups), sterilised by gamma rays or ethylene oxide
      (EtO), were retrieved after 1-12 years depending on different medical reasons and
      were studied by FTIR spectroscopy with derivatisation of oxidised species.
      Esters, acids and hydroperoxides were found under the surface of the EtO
      sterilised PEs up to 2 mm depth. The behaviour of gamma ray sterilised PEs is
      more complex due to the oxidation following the sterilisation process. Ester and
      acid formation might arise from the diffusion of components of synovial liquid or
      from the oxidation process, whereas hydroperoxide formation is thought to be due
      to the oxidation. Abrasion and delamination process is discussed considering the
      topological distribution of degradation products.

PMID- 9758038
TI  - Biological evaluation of biphasic calcium phosphate ceramic vertebral laminae.
AB  - An artificial vertebral lamina with a dense inside surface and porous outside
      part, fabricated with a biphasic calcium phosphate (70% hydroxyapatite/30%
      tricalcium phosphate) (HA-TCP) ceramic (abbr. CVL), was evaluated by animal
      experiments. The animal experiments showed that at half a month postoperation, no
      bone formation occurred on the macropore surfaces of the implants, however,
      fibrous connective tissues and blood vessels had grown into the macropores,
      contributing to the early fixation of the CVLs. The degradation of TCP phase was
      detected through X-ray diffraction (XRD); in the meanwhile, needle-like and plate
      like crystals were found in the materials through scanning electron microscopy
      (SEM), and infrared spectroscopy (IR) observations showed that the carbonate
      apatites similar to bone apatites began to occur in the materials. At one month
      postoperation, the degradation of the TCP phase became moderate, new bone began
      to grow into the porous structures of the implants, and further degradation of
      the implants provided rich Ca and P ions for new bone formation. The newly formed
      bone in the macropores of the implants increased with implantation time. At one
      year postoperation, the implant was completely fused with natural bone on the
      interfaces between them, new bone had grown into most of the porous structures of
      the implants, and a natural bone tissue layer formed on the inside surface of the
      artificial vertebral lamina. The new bone tissue layer played a more effective
      role in protecting the spinal cord and improving the spinal stability in the
      later implantation time.

PMID- 9758039
TI  - Early peripheral nerve healing in collagen and silicone tube implants:
      myofibroblasts and the cellular response.
AB  - Injuries to peripheral nerves innervating a limb cause paralysis, and can
      necessitate amputation. The inability of the nerves to regenerate spontaneously
      and the limitations of autograft procedures led to the development of treatments
      involving insertion of the nerve ends into prosthetic tubular devices. Previous
      work showed that 'entubulation' of the nerve ends in a silicone tube containing a
      specific porous, resorbable collagen-GAG (CG) copolymer, serving as an analog of
      extracellular matrix, improved regeneration compared to an empty silicone tube.
      However, long-term treatment with silicone tubes produced constriction that
      caused partial degradation of the regenerated axons; for this and other reasons,
      implementation of a nondegradable tube may require a second surgical procedure
      for removal. In this study the silicone tube was replaced with porous and non
      porous collagen tubes in order to produce fully degradable devices. CG-filled
      collagen tubes and controls (CG-filled silicone tubes and empty collagen and
      silicone tubes) were implanted in a 10-mm gap in the rat sciatic nerve, with
      three rats in each group. The regeneration was evaluated after six weeks using
      light microscope images of cross sections of the nerve that were digitized and
      analyzed. Histograms of the diameters of the axons were generated and compared.
      The cellular response to the implanted biomaterials was assessed histologically,
      and immunohistochemistry was performed using an antibody to alpha-smooth muscle
      actin in order to determine the presence of myofibroblasts (contractile cells).
      Axonal regrowth was comparable in porous collagen, non-porous collagen, and
      silicone tubes filled with a CG matrix. These results support the implementation
      of a degradable collagen tube in place of a silicone device. Confirming earlier
      work, regeneration through the silicone and collagen tubes was enhanced by the CG
      copolymer, compared to empty tubes. A notable finding was a continuous layer of
      myofibroblasts on the surfaces of all of the six silicone tube prostheses, but on
      the inner surface of only one of six collagen tubes (Fisher's exact tests; P <
      0.01). This is the first report of contractile capsules around silicone tubes,
      and supports the use of degradable collagen tubes in peripheral nerve
      regeneration. Macrophages were found bordering both the silicone and collagen
      tubes, and in the case of the collagen tubes, appeared to be participating in the
      regulation of the tubes.

PMID- 9758041
TI  - Reverse transcription-polymerase chain reaction and immunohistochemical study of
      the expression of fibronectin mRNA in human submandibular salivary gland.
AB  - The alternative expression of fibronectin mRNA in submandibular salivary glands
      was analysed using three groups of polymerase chain reaction probes to amplify
      the cell-binding domain (CBD), and the extra domain (ED)-A and ED-B exon regions
      in five normal human adults. The fibronectin CBD region was fairly well expressed
      in the salivary gland while less than trace amounts of ED-A and ED-B exons were
      expressed. Immunohistochemical staining with an antihuman plasma fibronectin
      monoclonal antibody, which recognized specifically the CBD region, demonstrated
      definite positive cytoplasmic staining in the duct-cell area. On the other hand,
      an anticellular fibronectin ED-A-specific monoclonal antibody was very low
      positive in duct cells. The results suggest that salivary fibronectin is
      synthesized in the submandibular salivary gland only, and does not include the ED
      A segment. Furthermore, duct cells also produced fibronectin without ED-A.

PMID- 9758040
TI  - Three-dimensional culture of rat calvarial osteoblasts in porous biodegradable
      polymers.
AB  - Neonatal rat calvarial osteoblasts were cultured in 90% porous, 75:25 poly(DL
      lactic-co-glycolic acid) (PLGA) foam scaffolds for up to 56 days to examine the
      effects of the cell seeding density, scaffold pore size, and foam thickness on
      the proliferation and function of the cells in this three-dimensional
      environment. Osteoblasts were seeded at either 11.1 x 10(5) or 22.1 x 10(5) cells
      per cm2 onto PLGA scaffolds having pore sizes in the range of 150-300 or 500-710
      microm with a thickness of either 1.9 or 3.2 mm. After 1 day in culture, 75.6 and
      68.6% of the seeded cells attached and proliferated on the 1.9 mm thick scaffolds
      of 150-300 microm pore size for the low and high seeding densities, respectively.
      The number of osteoblasts continued to increase throughout the study and
      eventually leveled off near 56 days, as indicated by a quantitative DNA assay.
      Osteoblast/foam constructs with a low cell seeding density achieved comparable
      DNA content and alkaline phosphatase (ALPase) activity after 14 days, and
      mineralization results after 56 days to those with a high cell seeding density. A
      maximum penetration depth of osseous tissue of 220+/-40 microm was reached after
      56 days in the osteoblast/foam constructs of 150-300 microm pore size initially
      seeded with a high cell density. For constructs of 500-710 microm pore size, the
      penetration depth was 190+/-40 microm under the same conditions. Scaffold pore
      size and thickness did not significantly affect the proliferation or function of
      osteoblasts as demonstrated by DNA content, ALPase activity, and mineralized
      tissue formation. These data show that comparable bone-like tissues can be
      engineered in vitro over a 56 day period using different rat calvarial osteoblast
      seeding densities onto biodegradable polymer scaffolds with pore sizes in the
      range of 150-710 microm. When compared with the results of a previous study where
      similar polymer scaffolds were seeded and cultured with marrow stromal cells,
      this study demonstrates that PLGA foams are suitable substrates for osteoblast
      growth and differentiated function independent of cell source.

PMID- 9758042
TI  - Effects of inositol hexasulphate, a casein kinase inhibitor, on dentine
      phosphorylated proteins in organ culture of mouse tooth germs.
AB  - To study the effects of impaired protein phosphorylation on dentine formation and
      mineralization, inositol hexasulphate, an intracellular type I and type II casein
      kinase inhibitor, was used in an in vitro organotypic culture system. Mandibular
      first molar tooth germs were dissected from 18-day-old mouse embryos and cultured
      for 11 days with and without inositol hexasulphate at different concentrations.
      At 0.04-0.08 mM inhibitor, cellular alterations were not detected. Dentine
      displayed the characteristic purple-blue colour when Stains all, a specific stain
      for extracellular phosphoproteins, was used. At 0.1 mM, dentine failed to stain
      and mineralization did not occur, as seen from the von Kossa method. The presence
      of numerous lysosome-like vesicles inside cells indicated that the experiment was
      at the limits of cytotoxicity; higher concentrations induced severe cellular
      alterations. Therefore, quantitative radioautography was carried out on germs
      treated or not with the inhibitor at 0.1 mM. [33P]-phosphate incorporation showed
      that grain density in inhibited germs compared with that in control germs was
      about double in odontoblasts and half in the predentine/dentine compartment. In
      the presence of inositol hexasulphate the incorporation of [3H]serine into
      odontoblast cell bodies was unchanged between 2 and 24 h while in
      predentine/dentine, grain density was higher between 1 and 4 h, and reduced at 24
      h. Both with [33P]phosphate and [3H]serine, labelling was seen throughout the
      porous dentine formed in vitro and not as a band located at the
      predentine/dentine junction, as is the case in vivo. With [3H]proline, in the
      presence of the inhibitor, a small reduction of grain density occurred in cell
      bodies, no significant difference was seen between 1 and 4 h in
      predentine/dentine, and more silver grains were present after 24 h both in cells
      and in the matrix. The radioautographic data support the view that the inhibitor
      interacts mostly with post-transductional phosphorylation and does not alter
      significantly other cell synthetic pathways and functions. Finally, the
      experiments presented here confirm that phophorylated proteins have a key role in
      dentine mineralization.

PMID- 9758044
TI  - Factors affecting the development of carious lesions in bovine teeth in vitro.
AB  - This study aimed to determine the effect of temperature, duration of exposure,
      position on enamel surface, and type of demineralization solution on the
      production of caries-like lesions in bovine enamel in vitro, and to establish the
      conditions for the formation of artificial caries in bovine enamel. Caries-like
      lesions were produced in incisal, middle and cervical sites on enamel samples,
      with either an acidified hydroxyethylcellulose gel system or a partially
      saturated acidic buffer solution at either 20 degrees C or 37 degrees C for 3, 4,
      or 5 days. Lesion variables (mineral loss/lesion depth) were quantified. Regular
      subsurface lesions were produced in all specimens in acidic buffer solution
      within 3 days at either temperature. In gel, caries-like lesions were produced in
      62% of the specimens at 37 degrees C and in 49% at 20 degrees C, while the
      remaining specimens were either eroded or softened. Mineral loss and lesion depth
      were significantly greater with buffer than with gel, and with increased length
      of exposure in either solution. There were no significant differences in either
      variable with position or temperature in either solutions, though numerically
      both variables were greater at the cervical site, and at 37 degrees C in either
      solution. It was concluded that caries-like lesions can be consistently produced
      in bovine enamel with a partially saturated acidic buffer solution at 20 degrees
      C or 37 degrees C within 3 days.

PMID- 9758043
TI  - Localization of atrial natriuretic peptide receptors in the rat tongue and hard
      palate.
AB  - Atrial natriuretic peptide (ANP) receptors were characterized in rat oral mucosa
      using quantitative in vitro autoradiography and activation of particulate
      guanylyl cyclase (GC) by natriuretic peptides. Competition-binding analysis
      performed by quantitative in vitro autoradiography demonstrated specific
      [125I]rANP(1-28) binding sites in the tongue and hard palate. The precise
      location of this binding was revealed on the basal and parabasal cells of the
      epithelia by microautoradiography. The dissociation constant (Kd) and maximal
      binding capacity (Bmax) of these sites were 3.34+/-1.35 nM and 2.71+/-2.21
      fmol/mm2 on the epithelium of the tongue, and 4.09+/-1.52 nM and 3.45+/-3.01
      fmol/mm2 on the epithelium of the hard palate, respectively. Receptor subtypes
      were characterized by competition with des [Gln18, Ser19, Gly20, Leu21, Gly22]
      ANP(4-23) (C-ANP), a specific ligand for the clearance receptor (NPR-C). These
      binding sites were displaced by C-ANP with inhibition constant (Ki) of 8.96+/
      3.18 nM and Bmax of 2.89+/-2.45 fmol/mm2 on the epithelium of the tongue, and Ki
      of 9.12+/-2.71 nM and Bmax of 3.08+/-2.94 fmol/mm2 on the epithelium of the hard
      palate, respectively. Production of cyclic GMP by particulate GC in the
      epithelial membranes of the tongue and hard palate was stimulated by rANP(1-28),
      porcine brain natriuretic peptide (BNP)(1-26), and C-type natriuretic peptide
      (CNP)(1-22) in a dose-dependent manner. These results indicate that ANP-binding
      sites in the epithelium of the tongue and hard palate are mainly clearance
      receptors (NPR-C) but biological receptors (NPR-A and/or NPR-B) with GC activity
      are also present, and suggest that ANP may have a role in the proliferation of
      the oral epithelial cells, especially in the tongue and hard palate.

PMID- 9758045
TI  - Discoloration of dental carious lesions (a review).
AB  - The discoloration of dental carious lesions is a marked feature which has
      received relatively little attention from dental researchers. In this short
      review, possible causes are considered: the formation of Maillard pigments,
      melanins, and lipofuscins, and the uptake of food dyes, metals, and bacterial
      pigments. It is concluded that the Maillard reaction between proteins and small
      aldehydes produced by bacteria probably accounts for the discoloration.

PMID- 9758046
TI  - A pilot study of mineralization distribution in the cortical bone of the human
      mandible.
AB  - Twenty-three specimens from immediately anteroinferior to the mental foramen were
      obtained from male and female, dentate and edentate, human mandibles.
      Planoparallel 80 microm thick sections were prepared from the mandibular
      specimens and computerized quantitative microradiography undertaken, which
      allowed the production of mineralization frequency distribution curves and mean
      mineralization. No differences in mean mineralization with age, sex, presence or
      absence of dentition were found, but mineralization distribution curves indicated
      differences between males and females. Within the age range and small sample size
      examined (40-90 years) there were no age-related differences. There was a lower
      level of mineralization distribution in the edentulous than the dentate mandible.

PMID- 9758047
TI  - Geographic variations in the composition of ivory of the African elephant
      (Loxodonta africana).
AB  - Tracing the source of origin of illegal ivory will contribute to the
      identification of poorly managed game parks and facilitate steps taken to prevent
      the African elephant from becoming extinct. This study was aimed at establishing
      a database on the composition of ivory obtained from elephant sanctuary areas in
      Southern Africa. Fragments of elephant ivory from seven geographically distinct
      areas in South Africa, Namibia and Botswana were analysed for inorganic and
      organic content. A total of 20 elements was detected in the inorganic fraction of
      ivory, some in concentrations as low as 0.25 microg/g. The concentrations of
      calcium, phosphate, magnesium, fluoride, cobalt and zinc showed statistically
      significant differences (p < 0.007) between ivory obtained from different
      regions. Analyses of the organic fraction identified 17 amino acids. Ivory from
      arid regions showed significantly lower proline plus hydroxyproline content and
      under-hydroxylation of lysine residues. This study indicates that chemical
      analyses of ivory could be beneficial in tracing the source of illegal ivory.

PMID- 9758048
TI  - Scanning microradiographic studies of rates of in vitro demineralization in human
      and bovine dental enamel.
AB  - The aim was to measure frequently and with precision the local integrated mineral
      loss through small areas of the natural surface of human and bovine enamel during
      in vitro demineralization using an X-ray photon-counting system (scanning
      microradiography). The method used was an adaptation of photographic longitudinal
      microradiography in which the attenuation of X-rays through the enamel is
      measured in the direction of acid attack, i.e., normal to the enamel surface. The
      mass of mineral (assumed to be hydroxyapatite) per unit exposed area was measured
      over 15 microm dia. circles at a series of positions as a function of time in
      blocks of human and bovine enamel immersed in 0.1 mol/l acetic acid buffered to
      pH 4.0 with NaOH. There was an initial period (approx. 45 h for human, approx. 75
      h for bovine enamel) during which the mineral loss with time was sigmoidal,
      followed by a nearly linear loss for the remainder of the experiment, in some
      cases up to 500 h. The initial sigmoidal period may be due to properties of
      surface enamel or be associated with the development of a surface layer overlying
      subsurface demineralization. The essentially constant rate of mineral loss after
      the surface layer has formed confirms earlier observations and is consistent with
      a rate-limiting process occurring at the dissolving enamel surfaces of the
      advancing front, and not by transport of ions within the lesion. Small
      perturbations from a linear loss were seen, which were approximately periodic for
      human enamel. The slope of the linear period was rather constant within one human
      or bovine block, but variable between blocks without a clear distinction between
      human and bovine enamel.

PMID- 9758049
TI  - Cytokine production by cryopreserved human peripheral blood mononuclear cells in
      response to periodontal pathogens.
AB  - Freezing techniques provide a way of repeating and extending immunological assays
      by using frozen portions of an individual's peripheral blood mononuclear cell
      fraction. Earlier work shows that the lymphocytes that are stored frozen retain
      their ability to respond to polyclonal B-cell activators, mitogens, superantigens
      and bacterial extracts of oral interest. These studies extend previous findings
      by determining cytokine production by lymphocytes following frozen storage for up
      to 24 weeks. Production of interleukin (IL)-1beta, IL-2, IL-6, and tumour
      necrosis factor (TNF)-beta by stimulated lymphocytes after cyropreservation was
      not significantly different from those responses before storage, with one
      exception: IL-6 production was negligible after 24 weeks' frozen storage when
      thawed cells were cocultured with pokeweed mitogen. After stimulation with
      extracts from Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans,
      the proliferative capacity of the frozen cells was maintained as well as the
      production of IL-1beta, IL-2, and IL-6. TNF-beta was not produced in response to
      bacterial antigen stimulation. The ability of peripheral blood mononuclear cells
      to retain functional activity after frozen storage should permit more effective
      monitoring during longitudinal clinical studies and a better evaluation of
      changes in cytokine production in patients with advanced periodontitis both
      during and after treatment.

PMID- 9758051
TI  - Prevention: toward a golden age.

PMID- 9758050
TI  - Improved reproducibility of magnetic stimulation-evoked motor potentials in the
      human masseter by a new method for locating stimulation sites on the scalp.
AB  - In magnetic-stimulation studies where motor-evoked potentials (MEP) are measured
      on different occasions, accurate relocation of the stimulation site on the scalp
      is essential. Here a novel method of locating neural stimulation sites was tested
      and the reproducibility of MEPs in the human masseter assessed. The heads of the
      participants were immobilized in a plastic mask that incorporated a grid
      overlying the left cerebral hemisphere. A figure-of-eight coil was oriented with
      a micromanipulator. Electrodes were placed over the right masseter using a
      standardized method. Two discrete sites on the grid were stimulated alternately
      at threshold + 10% whilst participants clenched their teeth. Recordings were
      repeated after the mask and electrodes had been removed and replaced. Within
      individual participants, the latency and amplitude of the MEP were reproducible
      between trials and when the mask and electrodes were replaced. The new method
      appears to be accurate and practical when recording longitudinal MEP data in the
      masseter.

PMID- 9758052
TI  - Spread of vancomycin-resistant enterococci: why did it happen in the United
      States?
AB  - The question of why vancomycin-resistant enterococci (VRE) became epidemic in the
      United States can be answered on at least three basic levels: (1) molecular and
      genetic, (2) factors affecting host-microbe interactions, and (3)
      epidemiological. This article will address the epidemiological issues and seek to
      defend the assertion that, once VRE had evolved, its spread throughout hospitals
      in the United States was all but assured. Nosocomial VRE outbreaks were reported
      first in the mid- and late-1980s. Since that time, scientific reports of VRE have
      increased over 20-fold. Among hospitals participating in the National Nosocomial
      Infection Surveillance System from 1989 to 1997, the percentage of enterococci
      reported as resistant to vancomycin increased from 0.4% to 23.2% in intensive
      care settings and from 0.3% to 15.4% in non-intensive-care settings. Factors
      leading to the spread of VRE in US hospitals include (1) antimicrobial pressure,
      (2) sub-optimal clinical laboratory recognition and reporting, (3) unrecognized
      "silent" carriage and prolonged fecal carriage, (4) environmental contamination
      and survival, (5) intrahospital and interhospital transfer of colonized patients,
      (6) introduction of unrecognized carriers from community settings such as nursing
      homes, and (7) inadequate compliance with hand washing and barrier precautions.
      Guidelines developed by the Centers for Disease Control and Prevention's Hospital
      Infection Control Practices Advisory Committee address each of these factors. The
      impact of these guidelines on the spread of VRE within individual institutions
      has been variable, and the overall impact of the guidelines nationally is
      unknown.

PMID- 9758053
TI  - Spread of vancomycin-resistant enterococci: differences between the United States
      and Europe.
AB  - There are major differences in the epidemiology of vancomycin-resistant
      enterococci (VRE) between the United States and Europe. In contrast with Europe,
      VRE in the United States are resistant to many antibiotics, and there appears to
      be less genetic variability among these isolates. European VRE of human origin
      are usually susceptible to many other antibiotics and are highly polyclonal.
      These clinical isolates have the same susceptibility profiles as VRE isolated
      from animals. The differences in the spread of VRE between the United States and
      Europe might be explained by the overconsumption of glycopeptides and other
      antibiotics in hospitals in the United States and the use of avoparcin as a
      growth promotor in Europe.

PMID- 9758054
TI  - Methicillin-resistant Staphylococcus aureus and its relationship to antimicrobial
      use: possible implications for control.
AB  - The control of methicillin-resistant Staphylococcus aureus (MRSA) is still an
      unresolved issue in numerous healthcare institutions worldwide. Guidelines for
      the control of MRSA in hospitals focus on measures to control cross-transmission
      and prevent colonization, but rarely specifically mention the control of
      antimicrobial use. We reviewed the different types of evidence for a causal
      relationship between MRSA and antimicrobial use by classifying them in four
      categories: consistent associations, dose-effect relationships, concomitant
      variations, and arguments to support a plausible biological model to explain this
      relationship. Although the relative participation of cross-transmission and
      antimicrobial selection pressure in the level of MRSA observed in a healthcare
      setting remains to be determined, we found lines of evidence to support the
      existence of a relationship between MRSA and antimicrobial use in each of the
      four categories. This review points out the relative lack of studies specifically
      designed to investigate this aspect of MRSA epidemiology and the need to
      implement such studies quickly. In the meantime, the results presented here
      should encourage the implementation of antimicrobial-use improvement programs in
      hospitals in addition to existing infection control measures, which are still a
      priority in countries with high MRSA prevalence.

PMID- 9758055
TI  - Preventing antibiotic resistance using rapid DNA-based diagnostic tests.
AB  - Improved diagnostic procedures should be an effective way to control infectious
      diseases and the spread of antibiotic resistance. To do so, diagnostics will need
      to be obtained within 1 hour of sampling and will require nucleic acid-based
      amplification tests directly on the clinical specimen.

PMID- 9758056
TI  - Comparative and library epidemiological typing systems: outbreak investigations
      versus surveillance systems.
AB  - A number of high-resolution molecular typing systems have been developed in
      recent years. Their availability raises the new issues of selecting the method
      (s) best suited for a particular purpose and interpreting and communicating
      typing results. Most of the currently available methods are comparative only:
      they allow testing of a sample of isolates for delineation of those closely
      related from those markedly different in genomic backgrounds. This approach is
      adequate for outbreak investigation, allowing determination of clonal spread in a
      microenvironment and identification of the source of infection. Comparative
      methods with sufficient resolution for most pathogens include restriction
      fragment-length polymorphism (RFLP), pulsed-field gel electrophoresis (PFGE), and
      arbitrarily primed and randomly amplified polymorphic DNA-polymerase chain
      reaction (PCR) analysis. For surveillance systems, monitoring clonal spread and
      prevalence in populations over extended periods of time requires library typing
      systems. These must be standardized, must have a high throughput, and must use a
      uniform nomenclature. Promising or validated methods include serotyping,
      insertion sequence fingerprinting, ribotyping, PFGE, amplified fragment-length
      polymorphism (AFLP), infrequent-restriction-site amplification PCR,
      interrepetitive element PCR typing (rep-PCR) and PCR-RFLP of polymorphic loci.
      PCR methods generating arrays of size-specific amplicons (AFLP, rep-PCR) can be
      more reproducibly analyzed by using denaturing polyacrylamide gel or capillary
      electrophoresis with automated laser detection. Binary probe typing systems
      appear optimal and should be enhanced further through use of DNA chip technology.
      In these systems, amplification of polymorphic regions is followed by solid-phase
      hybridization with a reference panel of sequence-variant specific probes. The
      resulting binary type results allow determination of reproducible, numeric
      profiles. However, interpretation and nomenclature of typing results for large
      scale surveillance purposes still require a better understanding of population
      structure and microevolution of most microbial pathogens.

PMID- 9758057
TI  - Modeling measles, mumps, and rubella: implications for the design of vaccination
      programs.
AB  - Mathematical models of disease transmission are being used increasingly in the
      design of population-based vaccination programs. Their use is illustrated in a
      review of some modeling studies that have implications for the use of measles,
      mumps, and rubella vaccine. Investigations of vaccination strategy options yield
      predictions for effectiveness and cost-effectiveness analyses. A quantitative
      understanding of the factors affecting disease transmission enables the setting
      of targets for vaccination programs and underpins disease elimination
      initiatives.

PMID- 9758058
TI  - Nosocomial transmission of opportunistic infections.
AB  - Immunocompromised patients are at high risk for opportunistic infections.
      Traditionally, these infections were thought to arise from endogenous
      reactivation of previously acquired latent infections, and nosocomial
      transmission therefore was deemed to be so unlikely that no special infection
      control interventions were needed to prevent transmission in healthcare settings.
      However, new data have challenged this view and suggest that some opportunistic
      pathogens are transmissible from one immunosuppressed patient to another.
      Epidemiological investigations, molecular genotyping, animal studies, and air
      sampling experiments lend support to the hypothesis that reinfection with
      opportunistic pathogens does occur, that airborne transmission is possible, and
      that nosocomial spread is a plausible explanation for case clusters. Taken
      together, these observations support the view that some opportunistic infections
      are exogenous in origin and that additional epidemiological investigations are
      needed to define the true risk of nosocomial spread and need for isolation.

PMID- 9758059
TI  - Is Streptococcus pneumoniae a nosocomially acquired pathogen?
AB  - Streptococcus pneumoniae is most prominently a major cause of community-acquired
      infections of the respiratory tract, central nervous system, and bloodstream, but
      there is an increasing interest in its role in the epidemiology of hospital
      acquired infections. Penicillin-resistant pneumococcal strains appeared 3 decades
      ago and now are present worldwide, often displaying multiple resistance due to
      antibiotic selective pressure. Horizontal spread can cause either sporadic cases
      or hospital outbreaks, primarily in younger children and elderly patients.
      Pneumococcal transmission from one patient to another can be documented by
      polymerase chain reaction or pulsed-field gel electrophoresis typing. Nosocomial
      acquisition of infection, along with pediatric age, previous hospitalization, and
      previous beta-lactam therapy, are the main risk factors significantly associated
      with penicillin-resistant pneumococcal infections. Nosocomial acquisition also is
      associated with higher mortality from pneumococcal disease. The importance of
      penicillin resistance as a risk factor significantly associated with higher
      mortality from pneumococcal infection is found in some studies, but not in
      others. Mortality from pneumococcal pneumonia is approximately the same for human
      immunodeficiency virus (HIV)-infected patients without acquired immunodeficiency
      syndrome (AIDS) as for HIV-negative subjects, but it is significantly higher in
      AIDS patients. Penicillin-resistant strains are involved in the vast majority of
      hospital outbreaks, whether presenting as clinically manifest infection or a
      simple colonization. Pneumococcal vaccination is recommended universally in order
      to lower the incidence of invasive infection, although a number of problems can
      limit its effectiveness.

PMID- 9758060
TI  - Increasing bacteremia due to coagulase-negative staphylococci: fiction or
      reality?
AB  - BACKGROUND: The role of coagulase-negative staphylococci (CNS) in bacteremias
      continues to be controversial. Until the 1970s, CNS were mostly recognized as
      contaminants, being part of the cutaneous flora. Since then, several studies have
      reported increasing incidence and severity of infections due to CNS. PURPOSE: To
      review the literature concerning the epidemiology of CNS bacteremia in the United
      States and Europe with reference to the multiple definitions of infection versus
      contamination, considering the effect of potential biases influencing the
      validity of the reported results. METHODS: Literature search of the MEDLINE
      database from January 1980 to February 1998. Studies with fewer than 500 episodes
      of bloodstream infections or fewer than 100 episodes of CNS bacteremia were not
      included in the pooled analysis. RESULTS: (1) CNS remain the most frequent
      contaminants (58%-83% of positive blood cultures); (2) the proportion of all
      bloodstream infections caused by CNS is increasing (R=.51); (3) the overall
      incidence of true CNS bacteremia is increasing (R=.54, P=.0014); (4) comparing
      the United States to Europe, there is an increasing trend in the incidence of
      nosocomial bacteremia due to CNS in the United States (R=.82, P=.0006), but no
      trend is seen in European studies; (5) the mortality associated with true CNS
      bacteremia varies between 4.9% and 28%. DISCUSSION: This review confirms the
      increasing importance of CNS bacteremias, measured both as a proportion and as an
      incidence of bloodstream infections. The contributions of several possible
      explanations for the incidence increase and the difference between the United
      States and Europe need further evaluation: (1) increased recognition and
      awareness of CNS infections among clinicians; (2) a gradual change in the
      definition of true bacteremia from an obligatory two positive blood cultures to
      one positive blood culture associated with a clinical picture compatible with
      infection; (3) a change in blood culture practices and techniques; (4) an
      increase in the numbers of blood cultures performed, which is reported both in
      the United States and in Europe; (5) a shift toward more elderly patients with
      increasingly severe underlying illnesses; and (6) increasing use of intravascular
      devices. CONCLUSIONS: The apparent trend of increasing CNS bacteremia seems to be
      valid. Whether there is a real difference between the United States and Europe
      concerning the increase of CNS bacteremia is difficult to establish due to the
      large number of confounding factors. Few studies take into account the number of
      blood cultures performed or the use of intravascular devices to adjust for the
      observed trends. Further on-site surveillance studies are needed to investigate
      the phenomenon more extensively.

PMID- 9758061
TI  - Strategies for prevention of infection in short-duration neutropenia.
AB  - Although infection continues to be a major cause of morbidity and mortality in
      neutropenic patients, newer strategies have resulted in a shorter duration of
      neutropenia. The prime risk to patients with short-duration neutropenia (defined
      as neutropenia of less than 14 days) is bacterial infection, which is reduced by
      the administration of prophylactic antibiotics, and possibly by the use of clean
      food, sterile water, and protection against transmission of organisms from
      healthcare workers' hands.

PMID- 9758062
TI  - Occult nosocomial infections.
AB  - Even with a good surveillance program, nosocomial infections may be not
      recognized because of several reasons: absence of symptoms or prolonged
      incubation period (eg, viral bloodborne infections, tuberculosis); problems with
      the microbiological diagnosis, because adequate specimens may be difficult to
      obtain or special methods should be used (eg, fungal infections, virus, new
      agents); shorter hospital stays (eg, surgical-site infections); difficulty in
      distinguishing between nosocomial and community-acquired infections (eg,
      influenza); and failure to detect clinically relevant colonization (eg,
      multiresistant microorganisms). Because of the important potential consequences
      of occult nosocomial infections, specific surveillance programs should be
      designed to address these problems.

PMID- 9758063
TI  - Critical-care-unit bedside design and furnishing: impact on nosocomial
      infections.
AB  - Hospitals in the process of building or renovating intensive-care units (ICUs)
      often establish multidisciplinary design teams. However, these teams rarely
      include infection control professionals. Because nosocomial infection is common
      in the ICU, design features can affect the risk of infection transmission, and
      outbreaks can occur during construction, this exclusion seems short-sighted.
      Infection control professionals are familiar with the relevant research, as well
      as the regulations and guidelines related to ICU design and infection control
      practices. Not only is their input essential to the design and construction of
      safe and effective units but their presence on the design team can allow the
      prospective collection of comparative data to turn the building project into a
      research project.

PMID- 9758065
TI  - Gullible's travels.

PMID- 9758064
TI  - Outcomes and moral hazards in the medical culture of opioid phobia.

PMID- 9758066
TI  - An apologia in defense of pain medicine.

PMID- 9758067
TI  - An invisible history of pain: early 19th-century Britain and America.

PMID- 9758068
TI  - The problem of pain in the clinicopathological method.

PMID- 9758069
TI  - Perceived efficacy of pain clinics in the rehabilitation of injured workers.
AB  - OBJECTIVE: To assess the perceived efficacy of pain clinics in the rehabilitation
      of injured workers among four groups of professionals. DESIGN: A questionnaire
      was given to 351 subjects representing four professional groups: physicians,
      vocational rehabilitation counselors, staff at pain clinics, and employees of a
      workers compensation program. Subjects rated the effectiveness of pain clinics in
      eight specific functions, estimated the percentage of workers who return to work
      after pain clinic treatment, and indicated how soon after injury a worker should
      be referred to a pain clinic. RESULTS: Pain clinic staff consistently gave the
      most favorable ratings and workers compensation employees the least favorable
      ones. There was good agreement across professional groups regarding the need for
      early referral of injured workers to pain clinics and the specific functions that
      pain clinics carry out relatively well. Clinics were ranked as most effective in
      reducing workers' use of opiates, and as least effective in reducing workers'
      pain. Return-to-work estimates varied significantly across professional groups.
      Within professional groups, subjects with high estimates gave more favorable
      overall ratings to pain clinics. CONCLUSIONS: The results provide a profile of
      the perceived effectiveness of pain clinics in various functions and highlight
      the importance of getting accurate information about return to work rates
      following pain clinic treatment. They suggest that workers are not referred to
      pain clinics early enough.

PMID- 9758070
TI  - Can we screen for problematic back pain? A screening questionnaire for predicting
      outcome in acute and subacute back pain.
AB  - OBJECTIVES: Because musculoskeletal pain is the second most frequent reason for
      seeking health care, the aims of this study were to determine the value of
      psychosocial variables in evaluating risk for developing chronic back pain
      problems and to develop a screening methodology to identify patients likely to
      have a poor prognosis. STUDY DESIGN: A prospective study was conducted on
      consecutive patients with acute or subacute back pain, in which patients
      completed a screening questionnaire and were then followed up for 6 months to
      determine outcome. The primary outcome variable was accumulated sick leave.
      METHODS: One hundred forty-two consecutive patients were asked to complete a
      questionnaire designed for this study. This questionnaire contained 24 items
      concerning psychosocial aspects of the problem. Six months later, patients were
      contacted to complete outcome questions about accumulated sick leave. RESULTS: A
      total of 97% of the patients completed both questionnaires. Although patients, on
      average, improved greatly, 18% had 1-30 days and 20% had fewer than 30 days of
      sick leave during the follow-up period. Five variables were found to be the
      strongest predictors of sick leave outcome (fear-avoidance work beliefs,
      perceived improvement, problems with work function, stress, and previous sick
      leave), correctly classifying 73% of the patients as opposed to a chance rate of
      33%. A total score was evaluated as a means of judging risk and found to be
      strongly related to outcome. CONCLUSION: Potent psychosocial risk factors
      associated with future sick absenteeism were identified. Because the total score
      was related to outcome, the instrument may have use in screening patients with
      acute or subacute spinal pain in clinical situations.

PMID- 9758071
TI  - Analysis of peak magnitude and duration of analgesia produced by local
      anesthetics injected into sympathetic ganglia of complex regional pain syndrome
      patients.
AB  - OBJECTIVE: Pain-relieving effects of lidocaine/bupivicaine local anesthetic (LA)
      and saline (S) block of sympathetic ganglia (stellate block, 4 patients; lumbar
      sympathetic block, 3 patients) were compared in 7 complex regional pain syndrome
      (CRPS) patients on a double-blind crossover basis to evaluate the diagnostic and
      therapeutic value of local anesthetic sympathetic blocks. DESIGN: Patients rated
      their pain on a visual analog scale before and after blocks and were tested for
      mechanical allodynia one-half hour after blocks. Thereafter, they rated their
      pain intensity in diaries four times a day for 7 days. Each patient received two
      blocks, S and LA, and served as his own control. RESULTS: Both S and LA
      injections of sympathetic ganglia produced large reductions in pain intensity in
      6 of 7 patients 30 minutes after block. These large reductions were accompanied
      by the reversal of mechanical allodynia in both S and LA. The mean difference
      between initial peak reduction in pain intensity produced by saline (68.7%) and
      active local anesthetic (74.4%) did not approach statistical significance. In
      striking contrast, the mean duration of pain relief was reliably longer in the
      case of LA (3 days, 18 hours) as compared with S ( 19.9 hours), a difference that
      occurred in all 7 patients. In a larger sample of 41 CRPS patients, signs of
      sympathetic efferent blockade, including Homer' s syndrome or skin surface
      temperature change, were not predictive of initial peak magnitude of pain relief
      from sympathetic blockade but were predictive of duration of pain reduction.
      CONCLUSION: The combination of these results provides evidence that duration of
      pain relief is affected by injection of local anesthetics into sympathetic
      ganglia. These results indicate that both magnitude and duration of pain
      reduction should be closely monitored to provide optimal efficacy in procedures
      that use local anesthetics to treat CRPS.

PMID- 9758072
TI  - Homeopathic Arnica 30x is ineffective for muscle soreness after long-distance
      running: a randomized, double-blind, placebo-controlled trial.
AB  - OBJECTIVE: To determine whether homeopathic Arnica 30X can reduce muscle soreness
      following long-distance running more than a placebo. DESIGN: Randomized, double
      blind placebo-controlled trial. SETTING: Long-distance runs taking place in the
      community. SUBJECTS: A total of 519 runners anticipating delayed-onset muscles
      soreness after long-distance races. INTERVENTIONS: A homeopathic medicine (Arnica
      30x) and an indistinguishable placebo. OUTCOME MEASURES: Subjects completed a
      visual analog scale and Likert scale of muscle soreness every morning and evening
      for the 5 days following their race. Race time was also recorded. The main
      outcome measure was mean 2-day visual analog scores. RESULTS: Results were
      obtained from 400 subjects. Groups were well matched at baseline. Mean 2-day
      visual analog soreness scores for Arnica and placebo were 45.2 mm and 41.0 mm,
      respectively. The 95% confidence interval was between 8.81 mm in favor of placebo
      and 0.51 mm in favor of Arnica. No differences were found for Likert scores or
      race time. CONCLUSION: Homeopathic Arnica 30x is ineffective for muscle soreness
      following long-distance running.

PMID- 9758073
TI  - Comparison of integrated group therapy and group relaxation training for
      fibromyalgia.
AB  - OBJECTIVE: The efficacy of an integrated, psychological treatment program was
      tested in a controlled study involving 27 patients with chronic musculoskeletal
      pain (fibromyalgia). DESIGN: The experimental treatment program consisted of
      instruction in various self-help techniques (e.g., cognitive behavioral
      strategies, relaxation, physical exercises) as well as information on chronic
      pain. Control groups were instructed only in autogenic training. Measures of
      pain, daily activities, general symptoms, and psychological functioning were
      assessed before and after treatment, as well as at 4 months after termination of
      therapy (follow-up). RESULTS: At the end of treatment, 7 patients from the
      experimental group and 2 from the control group showed significant clinical
      improvement in 3 of 6 parameters (NS). At follow-up, the improvement was still
      present in 5 experimental cases but in none of the controls (p = 0.024).
      Successful patients had been sick for a shorter period of time and were less
      impaired by their condition. CONCLUSIONS: Psychological interventions in
      combination with physiotherapy can be effective in treating fibromyalgia
      patients, especially if applied early.

PMID- 9758074
TI  - Vibration pain provocation can improve the specificity of MRI in the diagnosis of
      symptomatic lumbar disc rupture.
AB  - OBJECTIVE: The purpose of this study was to determine if vibration pain
      provocation could be combined with magnetic resonance imaging (MRI) to increase
      its specificity in identifying symptomatic disc disruption identified by
      discography. DESIGN: Prospective single-blind study. SETTING: Data were collected
      at a spine specialty clinic and at a diagnostic imaging center. PATIENTS: A total
      of 206 discs in 78 patients (41 males, 37 females; average age, 39.7 years;
      range, 18-73 years) were evaluated by MRI, spinous process vibration, and
      discography. INTERVENTIONS: A hand-held prototype vibrator was applied to the
      spinous process of each intervertebral disc level to be evaluated. The type of
      pain provoked with vibration as well as with discography was recorded as
      painless, dissimilar to clinical pain, or similar/exact reproduction of clinical
      pain. The discograms and MRI scans were scored on a 0-4 scale. A system was
      defined for combining the vibration results with MRI. OUTCOME MEASURES: The
      results of the vibration and MRI were compared with the results of computed
      tomography/discography to determine how well the results of the evaluations
      agreed. RESULTS: Vibration pain provocation agreed with discographic pain
      provocation in 70.9% of the discs. The specificity of MRI compared with
      discographic findings was only 55.7%. However, this figure improved significantly
      to 81.3% when relying on the vibration pain provocation in discs with mild or
      moderate disruption. The sensitivity of the combined evaluation was 85.9% and the
      accuracy 83.0%. CONCLUSIONS: A small hand-held vibrator could produce pain
      provocation results similar to those obtained by discography. Results of this
      noninvasive pain provocation method can improve the specificity and accuracy of
      MRI in identifying symptomatic disc lesions.

PMID- 9758075
TI  - Controlled trial of Japanese acupuncture for chronic myofascial neck pain:
      assessment of specific and nonspecific effects of treatment.
AB  - OBJECTIVE: This article examines the specific and nonspecific effects of Japanese
      acupuncture on chronic myofascial neck pain in a randomized single-blind trial.
      DESIGN: Forty-six patients were randomly assigned to receive relevant
      acupuncture, irrelevant acupuncture, or no-acupuncture control treatment
      consisting of nonsteroidal anti-inflammatory medication. The two acupuncture
      groups underwent comparable light shallow needling. The irrelevant acupuncture
      group received acupuncture at specific sites not relevant for cervical pain.
      OUTCOME MEASURES: The study measures included the McGill Pain Questionnaire-Short
      Form (SF-MPQ), the Short-Form Health Survey (SF-36), the Symptom Checklist 90
      Revised (SCL-90-R), medication diary, and physiologic measures. The factors
      examined as predictors of outcome pain ratings were experience with, beliefs
      about, and knowledge of acupuncture before treatment; perceived efficacy,
      credibility, and logic of acupuncture; perceived competence of the acupuncturist;
      and painfulness of acupuncture. RESULTS: No differences were found among the
      three groups at baseline, except that the relevant acupuncture group reported
      having had more previous acupuncture treatments. No significant differences in
      terms of perceived credibility or perceived effectiveness of treatment were found
      between the two acupuncture groups. The relevant acupuncture group had
      significantly greater pre-/posttreatment differences in pain than the irrelevant
      acupuncture and control groups (p < .05). The nonspecific effects of confidence
      in the acupuncturist, willingness to try any treatment, mood, and physiologic
      effect of needling were not predictive of treatment outcome, whereas confidence
      in the treatment and past experiences with acupuncture did correlate
      significantly with a decrease in pain. CONCLUSIONS: Relevant acupuncture with
      heat contributes to modest pain reduction in persons with myofascial neck pain.
      Previous experience with and confidence in treatment help to predict benefit.
      Measurement of nonspecific effects of alternative therapy is recommended in
      future clinical trials.

PMID- 9758076
TI  - Central nervous system abnormalities in complex regional pain syndrome (CRPS):
      clinical and quantitative evidence of medullary dysfunction.
AB  - OBJECTIVE: Sensory and motor abnormalities are common among patients with complex
      regional pain syndrome (CRPS). The purpose of the present study was to define and
      characterize these abnormalities and to develop a hypothesis regarding the area
      of the central nervous system from which they derive. DESIGN: Data were acquired
      from study subjects using clinical examination and quantitative assessment of
      neurological function. Subjects were divided into four groups. CRPS patients were
      differentiated into two groups based on the presence or absence of sensory
      deficit on the face to clinical examination. The other two groups were composed
      of patients with other chronic pain syndromes and normal individuals without
      chronic pain or disability. Clinical and quantitative data were compared between
      groups. PATIENTS: One hundred forty-five CRPS patients, 69 patients with other
      pain conditions, and 26 normal individuals were studied. RESULTS: A high
      incidence of trigeminal hypoesthesia was observed in CRPS patients. CRPS patients
      with trigeminal hypoesthesia manifested bilateral deficits of sensory function,
      with a predominant hemilateral pattern. These patients also manifested bilateral
      motor weakness with a more prominent hemiparetic pattern. Both sensory and motor
      deficits were greatest ipsilateral to the painful side of the body. These
      features differed significantly from those of CRPS patients lacking clinical
      trigeminal deficit, other pain patients, and normals. A lower cranial nerve
      abnormality (sternocleidomastoid weakness) and a myelopathic feature (Hoffman's
      reflex) were more common in CRPS patients with trigeminal hypoesthesia.
      CONCLUSIONS: Nearly half of CRPS patients had abnormalities of spinothalamic,
      trigeminothalamic, and corticospinal function that may represent dysfunction of
      the medulla. One-third of the remaining CRPS patients had neuroimaging evidence
      of spinal cord or brain pathology. The majority of CRPS patients in this study
      have measurable abnormalities of the sensory and motor systems or neuroimaging
      evidence of spinal cord or brain dysfunction.

PMID- 9758077
TI  - Abolition of neurogenic pain by focal cortical ischemia.

PMID- 9758078
TI  - Lamotrigine can reduce neurogenic pain associated with multiple sclerosis.

PMID- 9758079
TI  - Response to "Taxonomy? Never again".

PMID- 9758080
TI  - The growing importance of systolic blood pressure.

PMID- 9758081
TI  - Importance of the blood pressure-heart rate relationship.
AB  - In studies of the effects of salt intake on blood pressure (SBP, MBP, DBP),
      influences on heart rate (HR) are usually neglected even though the longterm load
      on both left ventricle (LV) and systemic arteries (SA) is better related to the
      product of HR x SBP (or MBP) than to pressure alone. After all, altered salt
      intakes often induce considerable volume-related changes in HR, and the heart
      operates more economically at low HR and high stroke volume (SV). Thus, about 3/4
      of LV metabolism is used for the build-up of systolic tension, while the cost for
      SV expulsion, or for SV increases, is far lower. Moreover, low HR prolongs the
      diastolic period, so important for LV coronary supply. Against this background we
      have used results from studies in both rats and man, in which both BP and HR were
      followed during marked changes in salt intake, to explore how this affected the
      HR x SBP (or HR x MBP) product. Briefly, in ordinarily salt-resistant organisms,
      whether normo- or hypertensive, salt intake increases, which in man ranged from
      10-20 to 250-300 mM (in rats over 100-fold), if anything reduced the computed
      longterm load (HR x SBP, or MBP) on LV and SA, as consequences of an efficient
      reflex volume control. By contrast, in salt-sensitive man, HR reflex reductions
      to increased salt intake were almost absent despite substantial SBP elevations,
      suggesting the influence of a CNS suppression of bulbar reflex centres combined
      with CNS neurohormonal interference with renal salt volume excretion, as in SHR.

PMID- 9758082
TI  - The prevalence of isolated systolic hypertension in patients 60 years of age and
      over attending Australian general practitioners.
AB  - AIMS: To determine the prevalence of isolated systolic hypertension (ISH) in
      patients 60 years of age and over attending general practitioners, and the
      proportion of patients in whom blood pressure (BP) remains within the ISH range
      when measured on three successive occasions and when using home BP monitoring.
      METHODS: BP was measured in 38 832 patients. Patients categorized as having ISH
      were reviewed after one week. Patients who had BPs in the ISH range at the second
      visit were provided with a home BP monitor and attended again in one week's time
      for further clinic blood pressure measurements. RESULTS: 8.6% of all patients
      were classified as having ISH and 31.4% as having borderline ISH at the first
      clinic visit. ISH was twice as prevalent in patients receiving antihypertensive
      therapy (12.4%) than in those not on antihypertensive therapy (6.2%). Of the
      patients initially categorized as having ISH, and who attended all three clinic
      visits and completed the home BP monitoring, 52.3% were confirmed as having ISH,
      34.0% fell into the borderline ISH range and only 7.0% had a normal BP reading at
      the third clinic visit. The use of home BP monitoring produced similar results.
      CONCLUSION: ISH is present on first screening in approximately 8% of elderly
      Australian patients. This prevalence falls by about 50% when BP is measured on
      two further occasions, with most patients subsequently falling into the
      borderline ISH range. Home BP monitoring does not reduce the percentage of
      patients classified as having ISH on the basis of three clinic measurements.

PMID- 9758083
TI  - Influence of vascular load on plasma endothelin-1, cytokines and catecholamine
      levels in essential hypertensives.
AB  - In vitro studies demonstrated a relationship between ET-1 and basic Fibroblast
      Growth Factor (bFGF), and of bFGF with Platelet Derived Growth Factor (PDGF). The
      present study was carried out to investigate in vivo the behaviour after vascular
      stress of circulating ET-1, bFGF and PDGF, and catecholamines, and their
      relationship. In 12 healthy normotensives (NTs) and 15 essential hypertensives
      (Ehs) venous blood samples to determine circulating ET-1, bFGF and PDGF, and
      catecholamine (EPI and NE) levels were drawn before and at the third minute of a
      handgrip test. Blood pressures (BP) and heart rate were automatically recorded
      before starting, and at 1, 2, and 3 minutes during the test. The NTs showed, in
      basal condition, lower values than the EHs of all the examined parameters; later,
      the handgrip test induced significant increases in circulating levels of ET-1,
      bFGF and catecholamine. In the EHs at the third minute of the exercise
      significant increases in plasma ET-1 (p < 0.002), bFGF (p < 0.006), and EPI and
      NE (p < 0.0005) levels were observed. Systolic and diastolic BP significantly
      increased after handgrip test in NTs and EHs. Plasma ET-1 correlated with bFGF
      both before (p < 0.01) and at the acme (p < 0.05) of the isometric exercise. Our
      results show that in EHs plasma ET-1 and bFGF correlate each other, indicating
      that in human hypertension a linkage between ET-1 and bFGF exists.

PMID- 9758084
TI  - Validation of an oscillometric blood pressure measuring device: a substudy of the
      HOT Study. Hypertension Optimal Treatment.
AB  - The accuracy of a semi-automated oscillometric blood pressure measuring device
      (Visomat OZ D2 International) was studied by simultaneous comparison with a
      standard sphygmomanometer in 407 normotensive subjects and hypertensive patients.
      Four pairs of measurements, at least 1 min apart, were obtained from all
      patients. The oscillometric device tended to give lower measurements than the
      standard device; the mean difference was -0.9 mmHg for diastolic blood pressure
      and -6.4 mmHg for systolic blood pressure. The size of this difference was not
      dependent on the mean blood pressure. Intra-individual standard deviations were
      similar with the two techniques. The oscillometric device tended to produce
      higher readings on the first measurement than on the subsequent three, whereas
      the reverse was true of the standard sphygmomanometer. It is concluded that the
      oscillometric device used in the HOT Study provides reliable measurements of
      blood pressure. The slight difference in mean readings between the two methods is
      unlikely to be of importance for the comparison of differences in treatment blood
      pressure values in the HOT Study.

PMID- 9758085
TI  - Clonidine suppression test revisited.
AB  - BACKGROUND: The diagnosis of pheochromocytoma may be difficult because the
      clinical picture is variable. OBJECTIVE: The purpose of this paper is to report
      our experience and to review the published data on the diagnostic significance
      and risks of the clonidine suppression test in the diagnosis of pheochromocytoma.
      PATIENTS AND METHODS: 114 patients were evaluated for pheochromocytoma using the
      clonidine suppression test. RESULTS: The diagnosis was established in four
      patients. Overall accuracy of the test in our own series was 98% when the normal
      response to clonidine was defined as total plasma catecholamines of less than 500
      ng/L, or less than 70% of the baseline value. No serious complication was noted.
      CONCLUSION: Our data and the published series demonstrate that the clonidine
      suppression test is accurate and safe in patients with suspected
      pheochromocytoma.

PMID- 9758086
TI  - Reduction of cardiovascular structural changes by nifedipine GITS in essential
      hypertensive patients.
AB  - The aim of this study was to evaluate the effect of the calcium antagonist
      Nifedipine GITS in a double-blind, randomized comparison with the diuretic
      hydrochlorothiazide (HCTZ) on reduction of left ventricular (LV) mass and minimal
      vascular resistance in a group of essential hypertensives with left ventricular
      hypertrophy (LVH). The effects on blood pressure and on echocardiographic LV
      functional parameters were also analysed. After two months of randomized
      treatment with Nifedipine GITS or HCTZ, if diastolic blood pressure was > 90
      mmHg, a combination of the two drugs was given and was continued for 24 weeks. M
      mode, 2D-guided echocardiography was used to measure LV mass index (LVMI)
      according to the "Penn convention". Minimal vascular resistance was measured in
      the forearm, from arterial pressure and maximal blood flow, using a strain gauge
      plethysmography. All examinations were performed before and after 8 and 24 weeks
      of treatment. Changes in LVMI were analysed at 8 weeks and at 24 weeks in
      patients receiving monotherapy ("according to protocol" analysis), and also at
      the end of treatment in patients taking Nifedipine or HCTZ monotherapy or the
      combination of the two drugs ("intention to treat" analysis). Both Nifedipine and
      HCTZ significantly reduced systolic and diastolic blood pressure (p < 0.001),
      without any significant difference between the two drug treatments. Heart rate
      was not significantly modified by either treatment. A progressive decrease in
      LVMI was observed after 8 and 24 weeks of treatment with Nifedipine monotherapy
      (ANOVA, p = 0.03), while the decrease in LVMI during HCTZ treatment did not
      progress further at 24 weeks (ANOVA, p = 0.49). A significant reduction of
      minimal vascular resistance was observed in patients treated with Nifedipine GITS
      monotherapy (ANOVA, p = 0.001), but not in the HCTZ group (ANOVA, p = 0.06).
      Comparison of changes of forearm minimal vascular resistance, considering
      baseline values, could demonstrate a greater effect during Nifedipine monotherapy
      as compared to HCTZ monotherapy. In conclusion, in a group of hypertensive
      patients with LVH, treatment for 24 weeks with Nifedipine GITS alone or in
      combination with HCTZ induced a significant reduction in LVMI and of forearm
      vascular structural changes, as evaluated by minimal vascular resistance. The
      decrease of minimal vascular resistance was significantly greater in patients
      treated with Nifedipine monotherapy, as compared to those given HCTZ.

PMID- 9758087
TI  - Antihypertensive treatment with candesartan cilexetil does not affect glucose
      homeostasis or serum lipid profile in patients with mild hypertension and type II
      diabetes.
AB  - This multicentre, randomized, controlled clinical trial assessed the effects of
      candesartan cilexetil (cand.cil.), a novel angiotensin II antagonist selective
      for the AT1 receptor with long-lasting antihypertensive activity, compared to
      placebo on glucose homeostasis and serum lipid profile in mild hypertensives with
      type II diabetes. A total of 161 men and women, 30-75 years old, with mild
      hypertension (sitting diastolic blood pressure 90-100 mmHg) and type II diabetes
      (HbA1c 5.5-9.0%), both measured after a 4-week placebo run-in period, were
      randomized to double-blind treatment with cand.cil. 8 mg o.i.d. (n = 83) or
      placebo (n = 78). Dose was increased to 16 mg o.i.d. if diastolic blood pressure
      remained >90 mmHg. At randomization and after 12 weeks of treatment HbA1c
      (primary effect variable), blood glucose and the serum lipid profile (including
      total cholesterol, HDL and LDL cholesterol, triglycerides) were assessed. The
      statistical analysis of the differences between treatments was based on changes
      from randomization to the end of the study. Cand.cil. had no significant effect
      on HbA1c, blood glucose and serum lipids compared to placebo. The median HbA1c
      both at baseline and after 12 weeks was 7.1% in patients on cand.cil., and 7.2%
      and 7.1% in patients on placebo. The 95% confidence interval for the median
      difference in change between the groups was narrow (-0.25; 0.16), including zero,
      which excluded any clinically important difference. The same held true for blood
      glucose (-1.10; 0.20), total cholesterol (-0.40; 0.20) and the other lipid
      parameters. More than 60% of the patients reached a diastolic blood pressure <90
      mmHg; adverse events and withdrawals were similar in both groups. Thus, in
      patients with mild hypertension and type II diabetes, cand.cil. 8-16 mg o.i.d.
      for 12 weeks does not affect glucose homeostasis and serum lipids. Blood pressure
      was controlled in most patients, and cand.cil. was well tolerated.

PMID- 9758088
TI  - The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial of
      cardiovascular events in hypertension. Rationale and design.
AB  - Essential hypertension is a major Public Health issue. Although the number of
      treated hypertensive patients has increased, only 25% of treated patients have
      their blood pressure levels under control. The benefit of treating hypertension
      has been proven, but cardiovascular morbidity and mortality rates remain high.
      The ideal antihypertensive drug should not only normalize blood pressure levels,
      but also reduce the associated cardiovascular morbidity and mortality rates. The
      role of angiotensin II in systemic hypertension and its complications has been
      recently redefined. The potent trophic effects of angiotensin II on blood vessels
      and on cardiac cells have been well demonstrated, especially the role of
      angiotensin II in left ventricular hypertrophy, vascular hypertrophy, endothelial
      dysfunction, and congestive heart failure. Of all ongoing mortality and morbidity
      trials in systemic hypertension, VALUE (Valsartan Antihypertensive Long-term Use
      Evaluation) is the only one comparing an angiotensin II antagonist (valsartan)
      with a third-generation calcium channel blocker (amlodipine). The main hypothesis
      of the VALUE trial is that, for an equivalent decrease in blood pressure,
      valsartan will be more effective than amlodipine in decreasing cardiac mortality
      and morbidity. VALUE is a prospective, multinational, multicentre, double-blind,
      randomized, active-controlled, 2-arm parallel group comparison with a response
      dependent dose titration scheme. VALUE involves 14,400 patients in over 30
      countries, who will be followed for 4 years or until 1450 patients experience a
      primary endpoint. The population to be included in VALUE consists of hypertensive
      men and women, aged 50 years or older, and at a relatively high risk of
      sustaining a cardiovascular event. The high risk profile is defined taking into
      account age, gender, and a list of cardiovascular risk factors and disease
      factors. Risk factors are cigarette smoking, hypercholesterolaemia, diabetes
      mellitus, uncomplicated left ventricular hypertrophy, proteinuria, and high serum
      creatinine. Disease factors include documented history of myocardial infarction,
      peripheral vascular disease, stroke or transient ischaemic attack, or the
      presence of left ventricular hypertrophy with strain on the ECG. A unique feature
      of VALUE is the assessment of the predictive power of this cardiovascular risk
      factor scale in a large population of treated hypertensive patients. The trial
      started on 10 September 1997.

PMID- 9758089
TI  - Cardiovascular effects of dietary salts and isosorbide-5-mononitrate in
      spontaneously hypertensive rats.
AB  - The influence of isosorbide-5-mononitrate (IS-5-MN) on the cardiovascular effects
      of high dietary salt intake (NaCl, 6.6% of dry weight of food) and that of a
      potassium, magnesium and l-lysine-enriched salt alternative (Pansalt 10.5%,
      producing a 6.6% content of NaCl) was studied in spontaneously hypertensive rats
      in an 8-week experiment. Common salt produced a marked rise in blood pressure and
      induced cardiac and renal hypertrophy, while the salt alternative, although
      containing the same amount of NaCl, neither increased blood pressure nor caused
      any significant cardiac hypertrophy. IS-5-MN treatment at a daily dose of
      approximately 60-70 mg/kg (mixed with food) attenuated the rise in blood pressure
      induced by common salt, but did not prevent the cardiac or renal hypertrophy. IS
      5-MN did not offer any additional benefit to the use of the salt alternative diet
      alone in treatment of high blood pressure. Mesenteric arterial responses in vitro
      were examined at the end of the study. IS-5-MN treatment during the moderately
      low-salt (NaCl 0.7%) control diet tended to decrease the contractile response to
      noradrenaline and increase the relaxation to acetylcholine. Common salt, but not
      the salt alternative, induced a 50% increase in the 24-h urinary excretion of
      cyclic GMP. Both salt supplements induced an 8-9-fold increase in the excretion
      of calcium, and about a 2-fold increase in the excretion of phosphorus. Common
      salt also increased the excretion of magnesium by 50%. IS-5-MN treatment had no
      significant effect on the excretion of the mineral elements. Our findings show
      that increased intake of potassium and magnesium reduces the harmful effects of
      common salt. Pressure-independent mechanisms are involved in salt-induced left
      ventricular and renal hypertrophy, since they remained unaffected despite the
      prevention of the salt-induced rise in blood pressure by IS-5-MN treatment.

PMID- 9758090
TI  - Computer-assisted gait analysis in equine orthopaedic practice: the case for
      inverse dynamic analysis.

PMID- 9758091
TI  - Is it poor or loss of performance?: the science of explanation.

PMID- 9758092
TI  - Post traumatic keratouveitis in horses.
AB  - Traumatic keratouveitis in horses is characterised by a unilateral, aseptic,
      vascularising keratitis accompanied by moderate to severe anterior uveitis. In a
      series of 9 cases of post traumatic keratouveitis, topical and systemic
      nonsteroidal drugs and atropine were used to control the anterior uveitis while
      allowing spontaneous corneal healing. Among the 9 cases reported, 6 affected eyes
      previously treated with local corticosteroids took significantly longer to
      resolve when compared to 3 eyes in which corticosteroids had not been
      administered. It was concluded that, in cases of equine post traumatic
      keratouveitis, locally administered corticosteroids inhibit healing of damaged
      corneal stroma and, by prolonging the keratitis, perpetuate the concurrent
      anterior uveitis.

PMID- 9758093
TI  - Stress fractures of the vertebral lamina and pelvis in Thoroughbred racehorses.
AB  - Thirty-six Thoroughbred racehorses that died at California racetracks between
      October 1993 and July 1994 were evaluated for stress fractures in the caudal
      portion of the thoracic and lumbosacral regions of the spine and the pelvis. The
      lumbosacral spine and pelvis were collected, debrided of soft tissues and
      examined visually for the presence of an incomplete fracture line and focal
      periosteal proliferation, characteristic of a stress fracture. Sixty-one per cent
      of specimens had evidence of stress fracture in the caudal portion of the
      thoracic and lumbosacral regions of the spine and the pelvis. Vertebral lamina
      stress fractures were found in 50% of specimens and were positively associated
      with the severity of dorsal spinous process impingement and overall severity of
      articular process degenerative changes. Pelvic stress fractures affected 28 % of
      specimens and occurred more frequently in older horses. Pelvic stress fractures
      were positively associated with the severity of lumbar transverse process
      impingement and several ilial articular surface degenerative changes. A high
      prevalence of vertebral and pelvic stress fractures was noted in this sample of
      Thoroughbred racehorses that died because of unrelated injuries. Vertebral and
      pelvic stress fractures need to be considered in the clinical evaluation of
      horses with back problems or hindlimb lameness. Undiagnosed stress fractures of
      the vertebrae or pelvis could be a significant cause of poor performance and
      lameness in Thoroughbred racehorses.

PMID- 9758094
TI  - Net joint moments and powers in the equine forelimb during the stance phase of
      the trot.
AB  - The objective of this study was to provide normative data describing the net
      joint moments and joint powers for the stance phase of the forelimb in trotting
      horses. Kinematic and force plate data, synchronised in time and space, were
      collected for the right forelimb of 6 Warmblood horses moving at a trot. The 3-D
      kinematic data were collapsed onto a sagittal plane, and were combined with the
      vertical and longitudinal ground reaction forces and with segment morphometric
      data to calculate net joint moments in the sagittal plane across the distal
      interphalangeal (coffin), metacarpophalangeal (fetlock), carpal, elbow and
      shoulder joints. The joint mechanical power was calculated as the product of the
      joint moment and the joint's angular velocity. Major peaks on the moment and
      power curves were identified. Each joint showed consistent and repeatable
      patterns in the net joint moments and joint powers. During most of stance the net
      joint moment was on the caudal/palmar side of all joints except the shoulder. At
      the coffin joint the power profile indicated an energy absorbing function that
      peaked at 74% stance, which coincided with the maximal longitudinal propulsive
      force. The fetlock joint behaved as an elastic spring; energy was absorbed in the
      first half of stance as the flexor tendons and SL stored elastic energy, which
      was released in the second half of stance as a result of elastic recoil. The
      carpus did not appear to play an important role in energy absorption or
      propulsion. Both the elbow and shoulder joints showed what appeared to be phases
      of elastic energy storage and release in the middle part of the stance phase,
      followed by a propulsive function at the shoulder in the later part of stance.
      The fetlock, carpus and elbow showed virtually no net generation or absorption of
      energy. The net energy generation at the shoulder joint was approximately equal
      to the energy absorption at the coffin joint. In human subjects specific gait
      pathologies produce characteristic alterations in the shape of the power profile
      as well as changes in the amount of energy absorbed and generated at the joints.
      In horses evaluation of net joint moments and joint powers will further our
      understanding of the mechanics and energetics of lameness, and may prove to be a
      useful diagnostic tool. An understanding of the function and dysfunction of
      different anatomical structures will facilitate the interpretation of clinical
      findings in terms of mechanical deficits.

PMID- 9758095
TI  - Bone scintigraphy in the diagnosis of sacroiliac injury in twelve horses.
AB  - Nuclear bone scintigraphy was used to diagnose sacroiliac injury in 12 horses
      presented for nonspecific rear limb lameness. The most common history was
      decreased performance and/or a mild chronic rear limb lameness which could not be
      localised by routine lameness examination. The scintigraphic patterns of the 12
      affected horses were compared to 5 normal horses and 10 horses with lameness not
      related to the pelvic region. Subjective and quantitative evaluation of the bone
      scans clearly separated the 12 affected horses from the 5 normal horses and the
      10 horses with lameness from causes other than the sacroiliac joint disease. The
      12 affected horses had a scintigraphic pattern of moderate to marked increased
      uptake of the radiopharmaceutical within the sacroiliac joint region on the side
      of lameness. In contrast, the 5 normal horses and 10 horses scanned for other
      causes of lameness, had a symmetric, or only slightly asymmetric pattern of
      radioisotope uptake. Although nonspecific for the type of injury, nuclear bone
      scintigraphy is considered sensitive for the detection of sacroiliac injuries in
      horses.

PMID- 9758096
TI  - Clinical assessment of gas exchange in mature horses.
AB  - There are limited methods of assessing pulmonary function in horses at rest. We
      developed clinical techniques to measure gas exchange efficiency in horses and
      evaluated 3 groups of horses that were 1) asymptomatic based on auscultation with
      rebreathing, transtracheal aspirate cytology, and thoracic radiographs (n = 6),
      2) asymptomatic at rest but symptomatic with rebreathing (n = 11) and 3)
      symptomatic at rest (n = 9). Blood samples were obtained from the transverse
      facial artery and jugular vein. Maximal end-tidal CO2 tension (PETCO2) was
      measured by an infrared capnograph through a facemask. Alveolar O2 tension, dead
      space fraction (V(D)/V(T)), and physiological shunt fraction (Q(S)/Q(T)) were
      calculated using standard formulae. Arterial O2 tension in Group 1 horses (mean
      +/-s.d.103+/-3 mmHg) was significantly higher than in Group 2 or Group 3 horses.
      Q(S)/Q(T) in Group 1 horses (0.37+/-0.98%) was significantly lower than in Group
      2 and Group 3 horses. Mean +/-s.d.V(D)/V(T) in Group 1 horses (-18.2+/-3.1) was
      significantly lower than Group 3 horses but not Group 2 horses.

PMID- 9758098
TI  - Dextran-70 inhibits equine platelet aggregation induced by PAF but not by other
      agonists.
AB  - Dextrans of mean molecular weight 70 kDa (dextran-70) have had clinical use as
      anti-thrombotics in man. A major part of the anti-thrombotic action is mediated
      via inhibition of platelet function. Greatorex (1975, 1977) treated
      thromboembolic colic in horses with infusions of dextran-70 and reported a 90%
      recovery rate, but this treatment is nonetheless rarely used. We have used an in
      vitro method to examine the effect of dextran-70 on equine platelet suspensions,
      in the hope that understanding the mechanism of action of dextran-70 might lead
      to the development of alternative therapeutic agents. The effects of dextran-70
      on equine platelets occurred immediately in vitro with an initial activation and
      shape change. Subsequent assessment of aggregation revealed a dose-dependent
      specific inhibition of platelet-activating factor (PAF)-induced aggregation,
      significant in rate of aggregation at dextran-70 concentrations >40 g/l (P<0.05)
      and in extent of aggregation at dextran-70 concentrations >50 g/l (P<0.05). Pre
      incubation with 60 g/l dextran-70 significantly inhibited the rate and extent of
      aggregation in response to PAF (1 nmol/l) (P<0.001 and P = 0.003, respectively)
      but this was not dependent on the duration of pre-incubation (from 0 to 150 min).
      No effects were seen when the agonist was adenosine 5'-diphosphate (200 nmol/l),
      collagen (10 mg/l), 5-hydroxytryptamine (100 micromol/l) or U44069 (600 nmol/l)
      (all P>0.1). Analysis of PAF concentration-aggregation curves after pre
      incubation with 60 g/l dextran-70 indicated significant noncompetitive inhibition
      by dextran-70 (P<0.001 for rate and extent of aggregation). The ability of
      dextran-70 to inhibit responses of equine platelets to PAF is probably an
      important component of its beneficial effect as an anti-thrombotic in colic
      cases.

PMID- 9758097
TI  - Maintenance of anaesthesia with sevoflurane and oxygen in mechanically-ventilated
      horses subjected to exploratory laparotomy treated with intra- and post operative
      anaesthetic adjuncts.
AB  - Eight healthy horses premedicated with xylazine and induced with ketamine were
      used to evaluate sevoflurane in oxygen for maintenance of anaesthesia during
      elective exploratory laparotomy. After orotracheal intubation, horses were
      hoisted, placed in dorsal recumbency on a padded surgery table, and received
      sevoflurane in oxygen for maintenance of anaesthesia. The horses were allowed to
      breathe spontaneously until instrumented; then, they were mechanically ventilated
      to maintain the PaCO2 between 35 and 45 mmHg. Systolic (SAP), diastolic (DAP),
      and mean (MAP) arterial blood pressures, heart rate (HR), ECG, respiratory rate,
      an estimation of the saturation of haemoglobin with oxygen in peripheral arterial
      blood (S(p)O2), nasal temperature, end-tidal CO2(ET(CO2)), end-tidal sevoflurane
      (ET(SEVO)), and vaporiser concentration were recorded every 5 min post induction;
      arterial blood samples were obtained soon after induction, at 30 min after
      induction, and every hour thereafter until surgery was completed. Recovery data
      including times from the sevoflurane vaporiser being turned off to first
      movement, to sternal recumbency, and to standing, number of attempts to stand,
      and recovery score (between 1 = safe, smooth and 6 = stormy, major injury to
      horse) were collected. Analysis of variance was performed using physiological
      data collected over 195 min of anaesthesia, the longest time period during which
      all 8 horses were instrumented. Time effects (P<0.05) for HR, SAP, DAP, MAP, and
      nasal temperature were identified. Heart rate peaked at 45 min and declined over
      the course of the procedure. Arterial blood pressure generally decreased over
      time. Body temperature decreased over time. From 15 to 195 min mean
      ET(SEVO)concentration ranged from 2.0 to 3.3%, while mean vaporiser settings
      ranged from 3.7 to 5.5%. Three horses received intra-operative ketamine; all
      horses received dobutamine infusions; and 2 horses received intra-operative
      calcium-dextrose. Total anaesthesia time was 222-316 min (mean+/-s.d.269+/-31
      min). Time from turning the sevoflurane vaporiser off to first movement was mean
      +/-s.d.18+/-15 min; to sternal recumbency was 54+/-22 min; to standing was 65+/
      27 min; and to returning the horse to the stall in the ward was 78+/-24 min. Six
      horses stood on the first attempt; 2 horses stood on the second attempt. The
      median recovery score was one (1-3). In conclusion, sevoflurane provided a
      stable, easily controllable anaesthetic plane during prolonged exploratory
      laparotomies; horses experienced smooth, safe recoveries after maintenance of
      anaesthesia with sevoflurane following routine anaesthetic induction and post
      operative xyalzine administration.

PMID- 9758099
TI  - An objective method for evaluating the flexibility of the back of standing
      horses.
AB  - The spinal movements in maximum arching, dipping and left and right lateral
      flexion were measured in 10 horses without signs of back pain. A system for
      motion analysis (Expert Vision System) was used to identify the position of the
      markers placed on the head, the spinous processes of T5, T10, T16, L3, and on 2
      of the sacral spines. By definition, the maximum of the spinal movement was set
      when the T16 marker reached its maximum deviation from the start position. The
      difference between start position and maximum position was presented as per cent
      of the horse's height at the withers. At T16 the mean results for flexion
      (arching) of the back were 5.9% (s.d.0.9), for extension (dipping) -2.4%
      (s.d.0.7), for flexion to the left 4.2% (s.d.1.1), and for flexion to the right
      5.3% (s.d.1.3).

PMID- 9758100
TI  - Equine TIMP-1 and TIMP-2: identification, activity and cellular sources.
AB  - Matrix metalloproteinases (MMPs) are the main enzymes involved in connective
      tissue turnover. Regulation of MMPs is achieved by controlling production,
      activation of the pro-enzymes together with the presence of inhibitors, such as,
      tissue inhibitors of metalloproteinases (TIMPS). The presence of TIMPs in equine
      synovial fluid was assessed by the ability of the fluid to inhibit equine MMP-9
      activity using a gelatin degradation ELISA. The cellular source of the TIMPs was
      determined using culture supernatants of resident articular cells (chondrocytes
      and synovial fibroblasts) and invading inflammatory cells (polymorph neutrophils
      [PMN] and peripheral blood monocytes [PBM]). The TIMPs were characterised further
      using reverse zymography, affinity chromatography and N-terminal amino acid
      sequencing. Synovial fluid was recovered from horses with articular sepsis and
      aseptic joint disease (AJD) and compared with that from normal horses (n = 4).
      TIMP activity was minimal in articular sepsis but significantly increased, albeit
      a small increase, in AJD when compared to normal (P<0.05). Cell culture
      supernatants from synovial fibroblasts, chondrocytes and PBMs contained TIMP
      activity, although supernatants from PMN cell culture did not. Reverse zymography
      of synovial fluid recovered from normal and AJD horses showed two protein bands,
      22 and 28 kDa in size, exhibiting inhibitory activity against MMP-9. Reverse
      zymography of culture supernatants of synovial fibroblasts and chondrocytes gave
      similar results whereas the culture supernatants from PMNs and PBMs showed the
      presence of only the 28 kDa protein. The N-terminal amino acid sequence was
      obtained for the 22 kDa protein and revealed a 66% homology with human TIMP-2.
      The identification of TIMPs in equine synovial fluids and cell culture
      supernatants suggest that they may have a fundamental role in the homeostasis of
      the normal joint and in the excess proteolysis which occurs in articular disease
      in the horse.

PMID- 9758101
TI  - Prevalence and characteristics of foal rejection in Arabian mares.
AB  - Separate surveys of Thoroughbred, Paint, and Arabian mare owners revealed a
      higher than expected rate of foal rejection in Arabian mares. A behavioural
      history form was submitted by owners of foal rejecting and nonrejecting Arabian
      mares, and maternal behaviour and management practices compared. Four generation
      pedigrees of rejecting and nonrejecting Arabian mares were also examined. Foal
      rejecting mares were more likely to avoid, threaten, squeal at, chase, bite, and
      kick their foals post partum than nonrejecting mares. Nonrejecting mares were
      more likely to lick, nicker and defend their foals post partum than rejecting
      mares. No statistically significant relationship was found between foal rejection
      and the type of breeding method (natural vs. artificial insemination), the
      presence of people at birth, the presence of nearby horses at birth, or
      assistance of the first nursing bout. The presence at least once of 1 of 2
      related sires was statistically higher in the pedigrees of rejecting vs.
      nonrejecting mares. Inherited and learned or environmental factors are likely to
      affect the expression of foal rejection behaviour.

PMID- 9758103
TI  - Cytology of 100 samples of abdominal fluid from 100 horses with abdominal
      disease.
AB  - A total of 100 samples of abdominal fluid (AF) from 100 horses with abdominal
      disease were evaluated by cytology. Cytology results were subsequently correlated
      with the final outcome of the disease. The horses were classified into 4 groups:
      Group I, horses that were treated with conventional (nonsurgical) therapy and
      recovered; Group II, horses that had surgery and survived; Group III, horses that
      had surgery but died; and Group IV, horses that were subjected to euthanasia
      prior to surgery. Statistical analysis showed that both nucleated cell count and
      total neutrophils were significantly higher in Group III than in Group I; and
      that the total mesothelial cells were significantly higher in Group III than in
      Groups I and II. No significant differences were found for erythrocyte counts and
      fluid total protein levels among the 4 groups. The findings suggest that
      classifying AF as transudate, modified transudate and exudate, as well as grading
      of inflammation as mild, moderate and severe on the basis of nucleated cell count
      (NCC) and fluid total protein (AFTP) can be greatly misleading. Differential
      identification of the nucleated cells was found to be far more reliable than the
      NCC alone, with or without the AFTP, and rendered valuable information, which
      overruled many times a diagnosis of transudate or modified transudate. Bands,
      metamyelocytes, toxic changes, plasma cells, and neutrophils penetrating rafts or
      fronds of mesothelial cells, supported a diagnosis of inflammation, even when the
      NCC, and the AFTP (interpreted according to currently accepted values) suggested
      otherwise. Several morphological features were found, including some cell types
      for which little or no mention was found at all in 22 major studies of this fluid
      in horses. Among these were 'reddish neutrophils', large granular lymphocytes
      (LGL), plasma cells, Mott cells, blasts, and a unique hitherto undescribed
      granular mesothelial cell.

PMID- 9758102
TI  - Total and respirable airborne dust endotoxin concentrations in three equine
      management systems.
AB  - The concentrations of total and respirable airborne endotoxin in the breathing
      zone of a pony in 3 different management systems, on 8 occasions, are reported.
      Airborne endotoxin concentrations in all 3 systems were lower than those reported
      for many other agricultural environments. However, total airborne endotoxin
      concentrations in many of the conventional stables exceeded those which can
      induce pulmonary inflammation and bronchial hyper-responsiveness in normal human
      subjects, and exceeded those which can induce bronchoconstriction in humans with
      pre-existing pulmonary inflammation. Therefore, airborne endotoxin may contribute
      to the development of airway inflammation and dysfunction in conventionally
      stabled horses. Potentially detrimental effects of airborne endotoxins on the
      welfare and exercise performance of stabled horses can be reduced by maintaining
      horses in 'low dust' stables or at pasture, since these environments had
      significantly lower airborne dust and endotoxin concentrations.

PMID- 9758104
TI  - Ultrasonographic confirmation of a space-occupying lesion in the brain of a
      horse: choroid plexus papilloma.

PMID- 9758105
TI  - Induction versus Popper: substance versus semantics.
AB  - This article reviews concepts of classical logic and induction, with special
      attention to the controversies surrounding Popperian claims that induction is
      impossible and does not exist. I argue that some of the controversy is semantic,
      and hence Popperian criticisms of induction must be translated carefully into
      ordinary language to be appreciated by inductively oriented epidemiologists. With
      this translation, the substance of the debate is not whether induction is
      possible (it is) or exists (it does), but whether and how we should employ
      probabilistic reasoning about hypotheses in epidemiological inference.

PMID- 9758106
TI  - Occupational risk factors for lung cancer: a case-control study in West Germany.
AB  - BACKGROUND: The aim of this study is to evaluate carcinogens and occupations
      suspected to cause lung cancer and to generate new hypotheses about occupational
      risks. METHODS: In a hospital-based study 1004 incident lung cancer cases and the
      same number of population controls matched for region, sex and age were
      interviewed between 1988 and 1993 for their smoking and occupational history.
      Exposure assessment was based on 33 job-specific supplementary questionnaires.
      Conditional logistic regression was used to calculate odds ratios (OR) and to
      control for smoking and occupational asbestos exposure. RESULTS: Lifelong
      prevalence of exposure to asbestos was 20.5% for exposure of more than 940
      lifetime working hours among controls, corresponding to an OR of 1.62 (95%
      confidence interval [CI] : 1.28-2.05) that was reduced to 1.45 after adjustment
      for smoking (P < 5%). Statistically elevated risks after adjustment for smoking
      and asbestos were seen in metal production and processing workers, transportation
      workers and freight handlers, in the rubber and plastics industry, in metal
      production, in engine and vehicle building, and installation. Significantly
      increased OR after adjustment for smoking and asbestos that deserve further
      attention were seen in plastics processing workers (OR = 3.49), and sheet and
      structural metal workers (OR = 2.01 and 2.37, respectively). CONCLUSIONS: The
      results of the study confirm previously described occupational risks. Because of
      the possibility of controlling for occupational asbestos exposure, the study
      gives clear indications for prevention and further research.

PMID- 9758107
TI  - Lung and kidney cancer mortality associated with arsenic in drinking water in
      Cordoba, Argentina.
AB  - BACKGROUND: Studies in Taiwan have found dose-response relations between arsenic
      ingestion from drinking water and cancers of the skin, bladder, lung, kidney and
      liver. To investigate these associations in another population, we conducted a
      study in Cordoba, Argentina, which has a well-documented history of arsenic
      exposure from drinking water. METHODS: Mortality from lung, kidney, liver and
      skin cancers during the period 1986-1991 in Cordoba's 26 counties was
      investigated, expanding the authors' previous analysis of bladder cancer in the
      province. Counties were grouped a priori into low, medium and high arsenic
      exposure categories based on available data. Standardized mortality ratios (SMR)
      were calculated using all of Argentina as the reference population. RESULTS: We
      found increasing trends for kidney and lung cancer mortality with arsenic
      exposure, with the following SMR, for men and women respectively: kidney cancer,
      0.87, 1.33, 1.57 and 1.00, 1.36, 1.81; lung cancer, 0.92, 1.54, 1.77 and 1.24,
      1.34, 2.16 (in all cases, P < 0.001 in trend test), similar to the previously
      reported bladder cancer results (0.80, 1.28, 2.14 for men, 1.22, 1.39, 1.81 for
      women). There was a small positive trend for liver cancer but mortality was
      increased in all three exposure groups. Skin cancer mortality was elevated for
      women only in the high exposure group, while men showed a puzzling increase in
      mortality in the low exposure group. CONCLUSIONS: The results add to the evidence
      that arsenic ingestion increases the risk of lung and kidney cancers. In this
      study, the association between arsenic and mortality from liver and skin cancers
      was not clear.

PMID- 9758108
TI  - Helicobacter pylori infection and mode of transmission in a population at high
      risk of stomach cancer.
AB  - BACKGROUND: Helicobacter pylori (H. pylori) is a recognized cause of chronic
      gastritis and peptic ulcer disease, and is strongly suspected to play a role in
      the aetiology of stomach cancer but little is known about the mode of
      transmission. AIM: To determine the prevalence of H. pylori infection in children
      and investigate potential modes of transmission in rural China. SUBJECTS AND
      SETTING: We examined 98 children aged 3-12 years and 289 adults aged 35-64 years
      in a village in Linqu County, China, which has one of the highest rates of
      stomach cancer in the world. METHOD: H. pylori infection was determined by 13C
      urea breath test in children and by an enzyme-linked immunosorbent assay in
      adults. RESULTS: Among 98 tested children, 68 (69%) were H. pylori positive, but
      the prevalence rates varied as a function of age, rising from about 50% at ages 3
      4 to 85% at ages 9-10 before falling to 67% at ages 11-12. Boys had a higher
      infection rate than girls (77.8% versus 59.1%, P < 0.05). Among 289 adults, 195
      (68%) were H. pylori positive, with a somewhat higher rate of positivity in
      younger compared to older age groups. The prevalence of H. pylori infection
      clustered within families. In families with at least one infected parent, 85% of
      children were H. pylori positive, while in families with both parents uninfected,
      only 22% of children were H. pylori positive (odds ratio [OR] = 30.4, 95% CI :
      4.0-232). CONCLUSIONS: These findings demonstrate the acquisition of H. pylori
      infection during early childhood in a population at high risk of stomach cancer,
      in a manner consistent with a person-to-person mode of transmission between
      parents and children.

PMID- 9758109
TI  - A case-control study of hepatitis B and C virus infection as risk factors for
      hepatocellular carcinoma in Henan, China.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers in
      the world and is particularly prevalent in China. China is also a hyperendemic
      area for hepatitis B virus (HBV) infection. Although a strong association between
      HBV infection and HCC has been established previously, the role of hepatitis C
      virus (HCV) infection and the interaction between HBV and HCV in the development
      of HCC has not been adequately explored. The major objective of this study is to
      determine the relationship between HBV or HCV infection and HCC by use of case
      control study in Henan, China. METHOD: In all, 152 HCC patients and 115 control
      patients were collected from four hospitals in Henan, China between January 1994
      and October 1995. The demographic characteristics of the two groups were
      comparable. In further analysis, a 1:1 pair-matched case-control study was
      performed. Of 152 HCC patients, 113 were randomly selected to be pair-matched by
      sex and age (+/-5 years) to controls with non-hepatic disease. All the cases and
      controls were interviewed during hospitalization by two specially trained
      interviewers using a standard questionnaire. All sera were tested for HBV and HCV
      markers. Odds ratios (OR) and 95% CI for HCC risk factors were calculated by
      logistic regression model controlling for possible confounding factors such as
      sex and age. The multivariate analysis was done on the basis of the univariate
      analysis. RESULTS: The results of this study indicated that the prevalence of
      hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV) were much
      higher in HCC patients (63.2% and 11.2% respectively) than in the control
      patients (5.2%, 3.5%). The difference between two groups was significant (P <
      0.05). Risk factor analysis revealed that both HBV and HCV infection were
      important factors for HCC in Henan, China and HBV appeared to have a key role in
      the development of HCC. Odds ratios of HBsAg and HBV infection were 28.82 (95%
      CI: 11.18-78.78) and 31.22 (95% CI: 13.86-72.15), respectively. Moreover, the
      risk of developing HCC increased significantly and showed an additive effect when
      both viral markers of HBV and HCV infection were considered (OR = 42.85). Results
      from the 1:1 pair-matched case-control study also showed that HBV infection was
      an important risk factor for HCC, which was consistent with the results from the
      group-matched case-control study. CONCLUSION: This is the first reported case
      control study of HCC in Henan, China. This study provides further evidence that
      chronic HBV infection is strongly associated with the development of HCC among
      this population. Our results have demonstrated that HCV and HBV infection are
      independent and probably additive risk factors for HCC.

PMID- 9758110
TI  - An international case-control study of adult glioma and meningioma: the role of
      head trauma.
AB  - BACKGROUND: Increased brain tumour risk after head trauma suggested by case
      reports and clinical series has been previously studied epidemiologically with
      mixed results. An international multicentre case-control study investigated the
      role of head trauma from injury or sports participation in adult brain tumour
      risk. METHODS: In all, 1178 glioma and 330 meningioma cases were individually or
      frequency matched to 2236 controls. Only exposures that occurred at least 5 years
      before diagnosis and head injuries that received medical attention were
      considered. RESULTS: Risk for ever having experienced a head injury was highest
      for male meningiomas (odds ratio [OR] = 1.5, 95% confidence interval [CI] : 0.9
      2.6) but was lower for 'serious' injuries, i.e. those causing loss of
      consciousness, loss of memory or hospitalization (OR = 1.2, 95% CI: 0.6-2.3).
      Among male meningiomas, latency of 15 to 24 years significantly increased risk
      (OR = 5.4, 95% CI: 1.7-16.6), and risk was elevated among those who participated
      in sports most correlated with head injury (OR = 1.9, 95% CI: 0.7-5.3). Odds
      ratios were lower for male gliomas (OR = 1.2, 95% CI : 0.9-1.5 for any injury; OR
      = 1.1, 95% CI: 0.7-1.6 for serious injuries) and in females in general.
      CONCLUSIONS: Evidence for elevated brain tumour risk after head trauma was
      strongest for meningiomas in men. Findings related to sports should be
      interpreted cautiously due to cultural variability in our data and our lack of
      complete data on physical exercise in general which appeared to be protective.

PMID- 9758111
TI  - Urbanization and childhood leukaemia in Taiwan.
AB  - BACKGROUND: In the 1980s socioeconomic development was dramatically rapid in the
      urbanized municipalities of Taiwan due to a prospering economy. This study
      addressed the question: Could differences in the incidence of childhood leukaemia
      (age <15) be demonstrated between urban and rural communities in Taiwan between
      1981 and 1990? METHODS: The log-linear regression model was used to assess the
      effects of age, level of urbanization, and calendar year on the variation of
      childhood leukaemia incidence rates between 1981 and 1990. RESULTS: Between 1981
      and 1990, the overall incidence rate of childhood leukaemia increased by 20%
      (rate ratio (RR) = 1.2, 95% CI: 1.0-1.5). As compared to rural areas,
      metropolitan regions showed a significantly higher incidence rate during the
      study period (RR = 1.3, 95% CI: 1.1-1.6). This urban-rural difference was
      particularly notable among children <5 years old (RR = 1.5, 95% CI: 1.2-1.9).
      Dose-response analysis further indicated that risk of childhood leukaemia was
      monotonically associated with levels of urbanization. The significant gradient in
      the risk of childhood leukaemia with urbanization was contributed solely by
      children in the 0-4 years age group. CONCLUSIONS: We noticed a relationship
      between urbanization and risk of leukaemia in children. Because of a dramatic
      influx of people into metropolitan areas during the 1980s, our findings may have
      provided support for the putative association between 'population mixing' or
      'population density' and risk of childhood leukaemia. Whether such association
      can be attributable to virus infection or other aetiologically related
      leukemogens warrants further investigations.

PMID- 9758112
TI  - Serum folate and chronic disease risk: findings from a cohort of United States
      adults.
AB  - BACKGROUND: Previous studies have suggested that folate may provide protection
      against various chronic conditions. METHODS: We examined the effect of serum
      folate concentration on mortality and chronic disease incidence in a nationally
      representative sample of 3059 adults of the National Health and Nutrition
      Examination Survey Epidemiologic Follow-up Study who were first examined from
      1971 through 1975 and who were followed for about 19 years through 1992.
      Proportional hazards regression was used to estimate hazard ratios for the lowest
      quintile of serum folate compared with the highest quintile for selected causes
      of death and disease incidence. RESULTS: The hazards ratio for all-cause
      mortality was 1.18 (95% CI: 0.91-1.52); for mortality for diseases of the
      circulatory system, 1.31 (95% CI: 0.82-2.12); and for cancer mortality, 0.99 (95%
      CI: 0.46-2.11). The hazard ratio for incidence of diseases of the circulatory
      system was 1.04 (95% CI: 0.86-1.26); and for cancer incidence, 1.00 (95% CI: 0.61
      1.66). The hazards ratio for all-cause mortality was 1.26 (95% CI: 1.01-1.57) for
      participants with a serum folate of <9.3 nmol/l compared with other participants.
      CONCLUSIONS: Low levels of serum folate may be associated with mortality from all
      causes and cardiovascular disease. However, the study lacked power to adequately
      examine the association between folate and disease-specific endpoints. Additional
      studies, using serum and other measures of folate nutritional status, are needed
      to examine the relationship between folate nutrition and other more specifically
      defined health outcomes.

PMID- 9758113
TI  - Acute myocardial infarction case fatality, incidence and mortality rates in a
      population registry in Gerona, Spain, 1990-1992. REGICOR Investigators.
AB  - BACKGROUND: Community-based registries provide the best approach to assessing the
      impact of myocardial infarction (MI) in a population. The objective of the
      present study was to determine MI mortality, incidence, attack rate and 28-day
      case fatality in the province of Gerona, Spain from 1990 to 1992. METHODS:
      Standardized methods were used to find, register and classify MI cases in that
      population (509628 inhabitants) as definite, possible and insufficient-data MI.
      RESULTS: Of the 1456 cases fulfilling eligibility criteria, 850 (58.4%) were
      classified as definite MI, 162 (11.1%) as fatal possible MI, 232 (15.9%) as no MI
      and 160 (11.0%) as fatal insufficient data. The 1990-1992 age-standardized
      incidence rates (first MI cases only) for definite and fatal possible MI were
      140.8 per 100000 men and 20.4 per 100000 women, all aged 35-64 years; attack
      rates (first and recurrent MI cases) were 182.9 and 24.5, and mortality rates
      46.4 and 5.8, respectively. Case fatality at 28 days was 27.4% and 19.9% in men
      and women, respectively, but women died later over that period. With respect to
      men, the age-adjusted risk among women of dying within 28 days post-MI was 1.26
      (95% confidence interval [CI]: 0.94-1.69). CONCLUSIONS: Myocardial infarction,
      incidence, mortality rates and case fatality in Gerona are among the lowest in
      the world. Age-adjusted case fatality within 28 days is only marginally higher in
      women than in men, but fatal cases occur later within this period in women.

PMID- 9758114
TI  - Regional serum cholesterol differences in Belgium: do genetically determined
      cardiovascular risk factors contribute?
AB  - BACKGROUND: Differences in serum lipid distribution and mortality from ischaemic
      heart disease have repeatedly been reported between Belgian northerners and
      southerners. We investigated whether serum lipoprotein(a) (Lp(a)) and
      apolipoprotein (apo) E polymorphism were involved. METHODS: Fasting serum lipids,
      apo A-I and B, and Lp(a) levels were examined in randomly selected, 20-39 year
      old Belgian males and females from the north (Flanders) and the south (Wallonia)
      of Belgium (N = 900). Apo E phenotype distribution was investigated in random
      subsamples from either region (N = 249). RESULTS: Mean serum cholesterol, low
      density lipoprotein cholesterol (LDL-c), apo B and triglyceride levels were
      higher in Walloons compared to Flemings within each gender, the difference being
      significant in 30-39 year old males. Average high density lipoprotein cholesterol
      and apo A-I levels were significantly lower in 30-39 year old male southerners,
      compared to their northern counterparts. Median Lp(a) was 67 mg/l in northerners
      and 75 mg/l in southerners (NS). The apo E phenotype distribution was similar in
      both regions (chi2 = 7.213; d.f. = 5; P = 0.2053), whereas the average effects of
      the apo E alleles differed between the regions. In southerners the epsilon4
      effect upon adjusted apo B and LDL-c levels was approximately+12% and the
      epsilon2 effect was approximately-15%; in northerners the epsilon4 and epsilon2
      effects were approximately+5% and approximately-25%, respectively. The apo E
      polymorphism did not affect serum Lp(a) levels. CONCLUSIONS: Regional cholesterol
      differences between Flemings and Walloons cannot be explained by differences in
      serum Lp(a) or apo E phenotype distribution. The less favourable epsilon2 and
      epsilon4 effects in southerners compared to northerners reflect modulation of the
      apo E gene by particular environments.

PMID- 9758115
TI  - Secular trends in blood pressure levels in Denmark 1964-1991.
AB  - BACKGROUND: Hypertension is an essential risk factor for development of
      cardiovascular diseases. Prospective studies show a reduction in risk of
      myocardial infarction with reduction of blood pressure. In Denmark there was a
      decrease in ischaemic heart disease mortality during the period (1968-1992) with
      around 34% in 30-65 year old men and 30% in women. OBJECTIVE: To assess the
      changes in casual blood pressure between 1964 and 1991 in seven cross-sectional
      population studies. SETTING: Centre of Preventive Medicine, University of
      Copenhagen, DK-2600 Glostrup. POPULATION: 10359 subjects, equal numbers of men
      and women, age exactly 30, 40, 50 and 60 years drawn as random samples from a
      background population of 300000 inhabitants and surveyed in 1964-1974 and five
      cross-sectional studies 1976, 1978, 1982-1984, 1986-1987 and 1991. METHODS: Blood
      pressure was measured according to WHO criteria by one technician in each survey.
      Alcohol consumption and physical activity were measured by a self-administered
      questionnaire. The weight and height were measured by standardized methods. Data
      on mortality from ischaemic heart disease were obtained from death certificates
      recorded by the National Board of Health. RESULTS: Blood pressure increased with
      increasing age in both genders and was significantly higher in men than in women.
      Median blood pressure in 50 year old men in 1964 was 135/85 mmHg and in 1991 it
      was 123/79, whereas in women in 1964 it was 140/85, against 119/74 in 1991. The
      prevalence of hypertensives among 30 and 40 year olds declined throughout the
      period. The performance of blood pressure measurements, technical variation,
      examination programme, seasonal variation and inter-observer variation were
      potential bias sources and influenced blood pressure levels, but cannot be shown
      to be responsible for the declining trend in blood pressure and hypertension.
      Women became a little more physical active in leisure time and men less active.
      Women consumed less alcohol than men, but the amounts slightly increased by the
      end of the period. Body mass index >25 was seen less frequently in women than in
      men and this increased in men over the period. Sale of antihypertensive drugs
      increased in Denmark over the 1964-1991 period. There seems to be good agreement
      between the changes in blood pressure in the population and the decline in
      mortality from stroke and coronary heart disease in Denmark, which is influenced
      by other risk factors as well. CONCLUSION: Blood pressure distributions have
      shifted towards lower values in 1964-1991. Prevalence of hypertension declined up
      to 1983. Risk factor changes as well as treatment for hypertension contribute to
      this.

PMID- 9758116
TI  - Unemployment, sociodemographic background and consumption of alcohol before and
      during the economic recession of the 1990s in Finland.
AB  - BACKGROUND: Some studies suggest that people's alcohol consumption increases
      during unemployment whereas others suggest the opposite. All studies, however,
      deal with situations marked by relatively low national unemployment rates. We
      studied alcohol use among individuals in relation to unemployment, education,
      marital status and sex during times of both low and high unemployment in Finland.
      METHODS: A group of 44391 respondents, aged 18-64 years, from nationally
      representative, consecutive annual samples of 5000 people from 1982 to 1995 was
      utilized. Overall response rate for men was 77% and for women 80%. RESULTS:
      Univariate analyses indicated that unemployment was associated with the amount of
      reported alcohol use. However, when logistic regression was used to analyse
      interactions between alcohol consumption, unemployment, education and marital
      status, the picture changed. During a low unemployment period (e.g. 1982-1990),
      being unemployed was not associated with the upper consumption level of alcohol
      use (defined as > or = 8 drinks/week for men, > or = 5 for women); nor was it
      during a high unemployment period (1991-1995), except among single people. During
      a high unemployment period poorly educated, single, unemployed men (odds ratio
      [OR] = 1.6, 95% confidence interval [CI] : 1.1-2.4), showed a significantly
      higher risk of upper level of alcohol consumption than otherwise similar but
      employed men (OR = 0.8, 95% CI: 0.6-1.0). The reference group consisted of highly
      educated, married, employed men who did not exceed the upper drinking limit.
      Similarly, the risk of upper consumption level drinking was significantly higher
      among highly educated, unemployed single women (OR = 2.4, 95% CI: 1.388-4.3) than
      among otherwise similar but employed women (OR = 1.1, 95% CI: 1.0-1.386).
      CONCLUSION: Thus, unemployment was weakly but significantly related to the upper
      consumption level of alcohol use among single people during the recession but not
      in the preceding period of economic growth.

PMID- 9758117
TI  - Prevalence of respiratory symptoms: marked differences within a small
      geographical area.
AB  - BACKGROUND: Geographical differences in prevalence of respiratory symptoms have
      been reported between countries in the EC Respiratory Health Survey (ECRHS). The
      differences between two neighbouring centres in the Antwerp area were surprising.
      We therefore extended the screening phase of this study to four other areas with
      different features in this region. METHODS: Methods and questionnaires of the
      first phase of the ECRHS were used to estimate prevalence rates of respiratory
      symptoms in all areas. Information on some major personal and environmental risk
      factors was also obtained. RESULTS: Higher prevalence rates of both respiratory
      symptoms and personal risk factors were recorded in Urban Antwerp, Berendrecht
      Zandvliet (harbour area) and Zwijndrecht (industrial area) than in Suburban
      Antwerp, Essen and Kasterlee (both rural). Neither personal nor environmental
      risk factors could provide satisfactory explanations for the area differences in
      symptoms. CONCLUSIONS: These large differences between groups of subjects living
      within a small geographical area prove that estimations of prevalence rates of a
      whole country based on measurements of prevalence in one specific area should be
      interpreted very cautiously. Epidemiological research within small geographical
      areas may thus still prove as informative as comparisons between countries for
      elucidating causes for different asthma prevalence.

PMID- 9758118
TI  - Sixteen-year coronary mortality in black and white men with diabetes screened for
      the Multiple Risk Factor Intervention Trial (MRFIT).
AB  - BACKGROUND: Risk of coronary heart disease (CHD) mortality associated with
      diabetes is high and it is unclear to what extent the high mortality is due to
      modifiable risk factors. To explore this, mortality and predictors of CHD death
      are compared in a large cohort of black and white men with diabetes. METHODS: In
      all, 610 black and 3997 white men who reported taking medication for diabetes and
      had no history of hospitalization for heart attack were screened by 22 centres
      for the Multiple Risk Factor Intervention Trial (MRFIT). At screening major risk
      factors for CHD were determined. Participants have been followed for an average
      of 16 years for vital status. Cause-specific mortality and predictors of CHD are
      compared for blacks and whites using proportional hazards regression. RESULTS:
      Serum cholesterol and systolic blood pressure levels were similar in blacks and
      whites with diabetes, while diastolic blood pressure and percentage of smokers
      were higher in blacks (89 versus 86 mmHg and 47% versus 34%) and median income
      was lower. Coronary heart disease was the leading cause of death, accounting for
      31% (68/221) and 44% (564/1293) of deaths among blacks and whites, respectively.
      Adjusted relative risks of CHD death and all cause mortality for blacks compared
      to whites were 0.71 (95% CI: 0.53-0.95) and 0.94 (95% CI: 0.75-1.11). Differences
      in reporting cause of death probably account for some of the black/white
      difference in CHD. High serum cholesterol, high blood pressure, and smoking
      increased risk of CHD death similarly in blacks and whites. CONCLUSIONS: Serum
      cholesterol, blood pressure, and smoking are major influences on CHD mortality
      risk in both white and black men with diabetes. High prevalence of these factors
      indicates substantial potential for CHD prevention in both ethnic groups.

PMID- 9758119
TI  - Risk of preterm delivery, low birthweight and growth retardation following
      spontaneous abortion: a registry-based study in Denmark.
AB  - BACKGROUND: Some studies have found an association between spontaneous abortion
      and adverse birth outcome in the subsequent pregnancy, but results are
      conflicting, maybe due to lack of confounder control. METHODS: Using population
      based registries we identified a cohort of 45 449 women having a livebirth
      preceded by a spontaneous abortion ('abortion cohort'), and a random sample of
      9752 women with two consecutive livebirths ('reference cohort'). We examined the
      risk of preterm (<37 weeks gestation) and very preterm delivery (<34 weeks), low
      birthweight and growth retardation in both births in the reference cohort
      compared with births following an abortion, controlling for social factors and
      interpregnancy interval. RESULTS: Compared to second births in the reference
      cohort, the abortion cohort had higher risks for preterm (odds ratio [OR] = 1.74,
      95% CI: 1.5-2.0) and very preterm delivery (OR = 2.17, 95% CI : 1.7-2.7), low
      birthweight (OR = 1.76, 95% CI: 1.5-2.1), and growth retardation (OR = 1.50, 95%
      CI: 1.4-1.6). In the reference cohort 3.9% of the pregnancies ended as preterm
      deliveries, 1 % as very preterm, 3.3% as low birthweight, and 8.1% as growth
      retarded. Women with two or more previous abortions had a higher risk for preterm
      and very preterm delivery. When first liveborns of women in the reference cohort
      were compared with first liveborns in the abortion cohort, only deliveries before
      34 and 37 weeks' gestation were associated with previous abortion. CONCLUSIONS:
      Spontaneous abortion is associated with preterm delivery (both <34 and <37 weeks)
      in the subsequent pregnancy. Women who become pregnant following an abortion
      should receive special attention in the antenatal clinics.

PMID- 9758120
TI  - Maternal cotinine level during pregnancy and birthweight for gestational age.
AB  - BACKGROUND: Recent studies have found that cotinine is a better predictor of
      birthweight than the number of cigarettes smoked in pregnancy. In this paper we
      test this hypothesis and use cotinine to explore the effect of environmental
      tobacco smoke (ETS) on birthweight. METHODS: In all, 1254 white women were
      interviewed at booking, 28 and 36 weeks about the number and brand of cigarette
      smoked. Cotinine was assayed from blood samples taken on the day of interview.
      The outcome was birthweight for gestational age. RESULTS: There was good
      agreement between self-reported smoker/non-smoker status and maternal cotinine
      with 1.3% women mis-reported as non-smokers at booking, 0.6% and 1.8% mis
      reported at 28 and 36 weeks respectively. Among smokers, cotinine was more
      closely related to birthweight than the number of cigarettes smoked at all three
      time points (r = -0.25 versus r = -0.16 at booking). A reduction in cotinine
      between booking and 28 weeks was associated with increased birthweight but the
      effect was not statistically significant. Among non-smokers the association
      between birthweight and cotinine was not statistically significant after
      adjusting for maternal height, parity, sex and gestational age. Difference in
      mean birthweight between non-smokers in the lower and upper quintiles of cotinine
      was 0.2% (95% CI: -2.4, 2.8). Pooling the results of 10 studies plus our own gave
      an estimated difference in mean birthweight between women unexposed and exposed
      to passive smoke of 31 g (95% CI: 19, 44). CONCLUSIONS: Cotinine is a better
      predictor of birthweight than the reported number of cigarettes smoked. If
      biochemical analysis is impossible, then self-reported smoking habit should be
      obtained prospectively using a structured approach. Any effect on birthweight of
      maternal passive smoking during pregnancy is small compared with the effects of
      maternal active smoking.

PMID- 9758121
TI  - Is there a consequence for fetal growth of having an unlike-sexed cohabitant in
      utero?
AB  - BACKGROUND: There is evidence to suggest a masculinizing effect on female
      intrauterine development in unlike-sexed twins. The purpose of the present report
      was to examine the possible effects of male presence on fetal growth in females
      by comparing mean birthweights in members from dizygotic unlike-sexed (DZU) pairs
      with those from dizygotic like-sexed (DZL) pairs. METHODS: The sample consisted
      of 1087 DZU and 1089 DZL twin pairs from the New Norwegian Twin Panel, which was
      established by identifying all twin births from 1967 to 1974 through the
      population-based Medical Birth Registry. RESULTS: The mean birthweight of females
      from DZU pairs was 2684+/-15 g (+/-SEM), as opposed to 2647+/-19 g in females
      from DZL pairs (P = 0.06). For males, the mean birthweight was 2812+/-16 g in DZU
      pairs and 2805+/-20 g in DZL pairs (P= 0.78). CONCLUSION: We found a tendency for
      the birthweight in females to be influenced by the presence of a male co-twin.
      This observation may have a biological significance and should lead to a close
      follow-up of DZU and DZL females with respect to hormone-sensitive disorders and
      reproductive ability.

PMID- 9758122
TI  - A comparison of three verbal autopsy methods to ascertain levels and causes of
      maternal deaths in Matlab, Bangladesh.
AB  - BACKGROUND: Verbal autopsies have been widely used to determine the levels and
      causes of maternal death but few studies have assessed the reliability of various
      methods. METHODS: We compared the levels and causes of maternal mortality in
      three data sources from Matlab, Bangladesh: (1) maternal deaths identified
      through a unique demographic surveillance system (DSS); (2) maternal deaths
      identified as a result of a previous detailed investigation into the levels and
      causes of maternal mortality; and (3) maternal deaths identified in the current
      special study. All studies used lay reporting, but differed in terms of the
      nature of the study, the sex of the interviewer, the format of the questionnaire
      and the procedure to derive the diagnosis. RESULTS: There were substantial
      disagreements between the routine reporting and the special studies. The DSS
      identified 67.2% of all deaths occurring during pregnancy or within 42 days
      postpartum (82.3% of direct obstetric deaths, 70.0% of deaths due to induced
      abortions and 42.4% of indirect obstetric deaths). Extending the definition of
      maternal deaths to 90 days postpartum increased the numbers of maternal deaths
      between 1987 and 1993 from 174 to 196. The two special studies also disagreed in
      the ascertainment of the causes of maternal deaths and yielded different cause of
      death distributions; the proportion of direct obstetric deaths (excluding
      abortion) was 50.4% in the current system compared to 44.5% previously (P =
      0.001). CONCLUSIONS: This study confirms the known difficulties in the
      ascertainment of the levels and causes of maternal mortality. The large
      disparities in the levels and causes of maternal mortality using three different
      methods of lay reporting in a population with an almost complete vital
      registration system add to the growing concern about the inaccuracies in the
      measurement of maternal mortality.

PMID- 9758123
TI  - Dental amalgam and multiple sclerosis: a case-control study in Montreal, Canada.
AB  - BACKGROUND: The aetiology of multiple sclerosis (MS) remains poorly understood.
      Dental amalgams containing mercury have recently been suggested as a possible
      risk factor for MS. METHODS: In a case-control study conducted between 1991 and
      1994, we interviewed a total of 143 MS patients and 128 controls, to obtain
      information on socio-demographic characteristics and the number of dental
      amalgams and the time since installation based on dentists' records. RESULTS:
      Neither the number nor the duration of exposure to amalgams supported an
      increased risk of MS. After adjustment for age, sex, smoking, and education those
      who had more than 15 fillings had an odds ratio (OR) of 2.57 (95% CI: 0.78-8.54)
      compared to those who had none; for individuals whose first amalgam was inserted
      more than 15 years prior to the study, we found an OR of 1.34 (95% CI: 0.38
      4.72). CONCLUSIONS: Although a suggestive elevated risk was found for those
      individuals with a large number of dental amalgams, and for a long period of
      time, the difference between cases and controls was not statistically
      significant.

PMID- 9758124
TI  - Comparison of key informant and survey methods for ascertainment of childhood
      epilepsy in West Bengal, India.
AB  - BACKGROUND: This study aimed to compare efficacy and cost of key informants and
      survey for ascertainment of childhood epilepsy within a treatment context in
      rural India. METHODS: The study was set in a non-governmental, community
      programme for the functional and socioeconomic rehabilitation of children with
      disabilities in rural West Bengal, India. Ascertainment was by two methods: house
      to-house survey of 15000 households and also by 430 key informants including
      village leaders, health workers and 670 schoolchildren. Methods were compared for
      positive predictive value, and sensitivity by capture-recapture technique. Ninety
      four children were enrolled into treatment. Predictors of treatment success were
      determined by multiple logistic regression analysis, giving adjusted odds ratios
      for remission. The costs of identifying one case and one treatment success were
      measured by costing personnel, materials and overheads. RESULTS: The survey was
      four times as sensitive as key informants although the positive predictive values
      were similar (36%, 40%). The survey had an absolute sensitivity of only 59%.
      Identification by key informants strongly predicted successful treatment outcome
      (odds ratio [OR] = 4.74, 95% confidence interval [CI] : 1.19-18.85). The cost of
      finding one case was US$11 and US$14, and of finding one successful treatment
      outcome US$35 and US$67 for informants and survey respectively. Key informants
      were essential in attaining longer term programme objectives. CONCLUSIONS: In the
      context of a treatment programme, key informants were the more cost-effective
      method, but community involvement was traded against low sensitivity in the short
      term. Overall ascertainment costs were significant in the context of primary
      health care in India.

PMID- 9758125
TI  - Bangungut in Manila: sudden and unexplained death in sleep of adult Filipinos.
AB  - BACKGROUND: Sudden and unexplained death in sleep (SUDS) is a leading cause of
      death of young men in several Asian populations, but the history and epidemiology
      of SUDS are not well known. METHODS: Autopsy records were reviewed in Manila in a
      study of the classification of SUDS. Death certificates filed in Manila during
      1948-1982 were then reviewed in a study of SUDS incidence. A nested case-control
      study of death certificates examined birthplace as an indicator of SUDS risk.
      RESULTS: The classification of SUDS cases in Manila during 1948-1982 (N = 722)
      evolved from the folk term, bangungut ('to rise and moan during sleep'), to
      various descriptions of post-mortem artefacts. The characteristics of victims in
      each of the groups were similar: 96% male, mean age 33 years, and modal time of
      death 3:00 a.m. The deaths were seasonal, peaking in December-January. SUDS
      victims were more likely than deceased controls to have been born outside of the
      Manila region (relative odds = 2.11; 95% CI: 1.59-2.78). The SUDS rate for men
      aged 25-44 years increased from 10.8 to 26.3 per 100000 person-years from 1948 to
      1982. CONCLUSION: The death certificate classification of SUDS in Manila has
      changed considerably, obscuring an increase in incidence. SUDS appears to be a
      regional phenomenon in Southeast Asia and environmental causes are likely because
      the deaths are seasonal, increased over the timespan studied, and are more common
      among migrants to Manila than among those born there.

PMID- 9758126
TI  - Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS)
      mortality in industrialized nations, 1987-1991.
AB  - OBJECTIVE: To compare patterns of human immunodeficiency virus (HIV)/acquired
      immunodeficiency syndrome (AIDS) mortality in 11 selected industrialized
      countries with highly developed death registration systems and a broad range of
      cumulative AIDS incidence rates. METHODS: Data on HIV/AIDS mortality were
      obtained from the World Health Organization (WHO) and Statistics Canada for the
      years 1987-1991. We obtained data for Australia, Canada, Denmark, France, the
      former Federal Republic of Germany, Italy, the Netherlands, New Zealand, Spain,
      Switzerland, and the US, stratified by sex and 5-year age groups. Population
      figures were obtained from national censal, post-censal or interpolated annual
      estimates compiled by WHO and from Statistics Canada. RESULTS: A total of 141534
      deaths were attributed to HIV/AIDS (126224 in men and 15310 in women) in the 11
      countries from 1987 to 1991. The majority of deaths (73.7%) occurred in the US.
      Other countries contributing substantially to the number of deaths were France
      (7.1%), Italy (4.9%), Spain (4.9%), former West Germany (3.5%), and Canada
      (3.0%). Age-specific death rates for men aged 25-44 years in 1991 were highest in
      the USA at 47.1 per 100000 population and highest for women in Switzerland at 7.7
      per 100000 population. Potential years of life lost (PYLL) before age 75 years
      were highest for males in the US (2388 per 100000 population) and for females in
      Switzerland (373 per 100000 population). The lowest rates were in New Zealand
      (339 per 100000 population in men and 6.5 per 100000 population in women).
      CONCLUSIONS: This historical demographic analysis indicates that mortality
      resulting from HIV infection and AIDS among men and women varies considerable by
      country. Rates of death were highest in the US and lowest in Australia, the
      Netherlands, and New Zealand.

PMID- 9758127
TI  - Socioeconomic geographical links to human immunodeficiency virus seroprevalence
      among childbearing women in Montreal, 1989-1993.
AB  - BACKGROUND: To describe the socioeconomic profiles of geographical areas on
      Montreal Island in which human immunodeficiency virus (HIV) seropositive women
      delivering live births between 1989 and 1993 reside. METHODS: Leftover dried
      blood spot filter paper specimens collected from newborns were irretrievably
      unlinked from identifying information prior to testing. Seroprevalence estimates
      were calculated based on Western blot confirmed positive samples. Using data from
      the Canadian census, Revenue Canada, and provincial birth records, the
      socioeconomic characteristics of postal zones in which seropositive mothers
      reside were described. RESULTS: Montreal Island had an overall 5-year HIV
      seroprevalence rate estimate of 16.6 (95% CI: 14.1-19.3) per 10000 childbearing
      women. Areas in which at least one seropositive woman gave birth had lower mean
      infant birthweights and higher percentages of single mothers and single-parent
      families. The HIV-positive neonatal blood specimens were more likely to originate
      from areas where a higher proportion of residents reported less education,
      greater unemployment, and lower income. CONCLUSIONS: Higher HIV infection rates
      were found among childbearing women from lower socioeconomic areas of Montreal.
      Increased understanding of the relationship between socioeconomic status and HIV
      acquisition and transmission is required to inform the development of targeted
      HIV prevention programmes.

PMID- 9758129
TI  - CD4+ lymphocytes and tuberculin skin test as survival predictors in pulmonary
      tuberculosis HIV-infected patients.
AB  - BACKGROUND: We analyse whether the tuberculin skin test is a good survival marker
      in a cohort of pulmonary tuberculosis patients with HIV infection (PTB/HIV). In
      all, 494 PTB/HIV patients were enrolled in Barcelona (Spain) between January 1992
      and December 1994 in the Tuberculosis Program of Barcelona. The main data problem
      was the large proportion of missing values in the covariates percentage of T CD4+
      lymphocytes and the tuberculin test results: only 157 patients (31.8%) had both
      covariates recorded. METHODS: Patients were dichotomized into two groups
      according to their level of immunosuppression (< or = 14 and >14% T CD4+ cells).
      First, we carried out the semiparametric and parametric complete case analysis.
      After this, we analysed the data assuming a missing at random non-response
      pattern. We developed a bootstrap approach where missing data in the markers are
      imputed via a two-way linear model. Using Weibull regression estimation, we used
      a multiple imputation scheme to estimate the parameters of interest. RESULTS: We
      found significative differences for the most immunosuppressed group when
      comparing positive tuberculin patients with those who were tuberculin negative.
      From a complete case approach and through a multivariate Cox analysis, we
      obtained a significant relative hazard of 0.3657 (95% CI: 0.13-1.02; P = 0.054).
      When a Weibull model was fitted, we estimated a constant relative percentile
      value of pR = 4.1329 (95% CI: 0.97-17.59). From a missing data approach, we
      obtain a higher constant relative percentile 5.48 (P = 0.079). CONCLUSIONS: The
      imputation method allows us to assess the protective character of positivity for
      the tuberculin test for the lowest CD4+ level. These findings strongly suggest
      the value of the tuberculin skin test as a qualitative measure of the
      immunological response and its interest for developing countries where specific
      laboratory tests are not affordable.

PMID- 9758128
TI  - Causes of death in a rural, population-based human immunodeficiency virus type 1
      (HIV-1) natural history cohort in Uganda.
AB  - BACKGROUND: While human immunodeficiency virus (HIV)-related causes of death have
      been well documented in developed countries, in Africa data are scanty and mainly
      based on autopsy studies from city hospitals which are highly selective and may
      not represent causes of HIV-associated deaths in the general population. This
      study, from a rural population, describes the causes of death in HIV-positive
      people and their HIV-negative controls. METHODS: A natural history cohort
      comprising HIV-1 infected participants and HIV-negative controls was established
      in rural Uganda in 1990. Causes of death were determined by reviewing the
      premorbid clinical and laboratory findings and from information obtained from
      relatives. Blindness to the deceased's HIV serostatus was maintained throughout.
      RESULTS: In all, 78 deaths occurred over a 6-year period: 63 deaths occurred in
      the HIV-positive cases (53 prevalent and 10 incident cases) and 15 deaths in the
      HIV-negative controls. Of the prevalent cases, 56%, and 9% the incident cases
      enrolled died, compared with 7% of the HIV-negative controls. Of the 55 HIV
      positive cases with sufficient data to establish cause of death, 52 (95%) were
      assessed as having HIV-associated deaths and 48 (87%) died in WHO stage 4 (AIDS).
      The main causes of death were wasting syndrome (31%), chronic diarrhoea (22%),
      cryptococcal meningitis (13%) and chest infection (11%). CONCLUSIONS: Our results
      represent an unbiased selection of deaths in a rural area. The HIV-positive cases
      have high death rates and die of HIV-related pathologies. The main causes of
      death reflect the WHO clinical case definition of AIDS. Cryptococcal meningitis
      is also a common cause of death in this population.

PMID- 9758130
TI  - Delayed-type hypersensitivity to Mycobacterium leprae soluble antigens as a test
      for infection with the leprosy bacillus.
AB  - BACKGROUND: Mycobacterium leprae (M. leprae) soluble antigen (MLSA) reagents have
      been developed with the aim of finding a reagent, comparable to tuberculin, which
      could identify individuals infected with the leprosy bacillus. They have yet to
      be evaluated fully in human populations. METHODS: More than 15000 individuals
      living in a leprosy endemic area of northern Malawi were skin tested with one of
      five batches of MLSA prepared using two different protocols. The main difference
      in preparation was the introduction of a high G centrifugation step in the
      preparation of the last three ('second-generation') batches. RESULTS: The
      prevalence of skin-test positivity (delayed-type hypersensitivity (DTH)) and
      association with the presence of a BCG scar were greater for first (batches A6,
      A22) than second (batches AB53, CD5, CD19) generation reagents. The association
      of positivity with M. leprae infection was investigated by comparing results
      among known (household) contacts of leprosy cases, and among newly diagnosed
      leprosy patients with those in the general population. While positivity to 'first
      generation' antigens appeared to be associated with M. leprae infection,
      positivity to later antigens was unrelated either to exposure to leprosy cases or
      presence of leprosy disease. There were geographical differences in the
      prevalence of DTH to the various batches, probably reflecting exposure to various
      mycobacteria in the environment. CONCLUSIONS: Our results suggest that the
      'second-generation' batches have lost antigens that can detect M. leprae
      infections, but that they retain one or more antigens which are shared between M.
      leprae and environmental mycobacteria. Natural exposure to these both sensitizes
      individuals and provides natural protection against M. leprae infection or
      disease. Identification of antigens present in these groups of skin test reagents
      may assist in production of improved skin test reagents.

PMID- 9758131
TI  - Estimates of the severity of illnesses associated with bathing in marine
      recreational waters contaminated with domestic sewage.
AB  - BACKGROUND: During the summers of 1989-1992 we conducted four randomized
      intervention trials at four separate UK bathing locations judged of acceptable
      quality under current USEPA and EU criteria. The results showed bathers to be at
      increased risk of gastroenteritis, acute febrile respiratory illness (ICD-9 461
      466, 480), ear and eye infections relative to non-bathers. The public health
      significance of these findings has been questioned based upon the unproven
      assumption that these illnesses are minor in nature and thus of questionable
      public health significance. METHODS: The severity of these illnesses or ailments
      in terms of duration of illness, percentage of participants seeking medical
      treatment, and number of days of lost normal daily activity among study
      participants reporting specific illnesses or ailments were assessed. In addition
      the attributable proportion of illness among the exposed (bathers) was calculated
      for each illness or ailment. RESULTS: Average duration of illness ranged from
      approximately 4 days to approximately 8 days depending on the specific illness
      reported. The percentage of study participants seeking medical treatment ranged
      from 4.2% to 22.2% while the percentage reporting the loss of at least one day of
      normal daily activity ranged from 7.0% to 25.9% depending on the illness
      reported. The overall percentage of each illness that can be directly
      attributable to exposure to marine waters contaminated with domestic sewage
      ranged from a low of 34.5% for gastroenteritis to a high of 65.8% for ear
      infections. CONCLUSIONS: To our knowledge, this is the first study to assess and
      report the severity of illnesses associated with bathing in recreational waters
      contaminated with domestic sewage. Illness associated with bathing in marine
      waters contaminated with domestic sewage can no longer be viewed as minor, and
      indeed can have a substantial impact on the public health.

PMID- 9758132
TI  - A methodological note on the selection of friends as controls.
AB  - A number of issues inherent in the selection of friends as controls in case
      control studies are illustrated in the light of a recent dietary study, based on
      hospital and friend controls. Preselection of certain characteristics of the
      controls by the interviewee is almost unavoidable. The choice of controls to be
      used in a case-control study must reflect the nature and type of hypothesis which
      is being tested. Advantages and drawbacks of potential control groups must be
      weighted against each other.

PMID- 9758134
TI  - Collagen fibre arrangement in the tibial plateau articular cartilage of man and
      other mammalian species.
AB  - Experimental animal models are frequently used to study articular cartilage, but
      the relevance to man remains problematic. In this study animal models were
      compared by examination of the collagen fibre arrangement in the medial tibial
      plateau of human, cow, pig, dog, sheep, rabbit and rat specimens. 24 cartilage
      samples from each species were prepared and maximum cartilage thickness in the
      central tibial plateau measured. Samples were fixed, dehydrated, freeze-fractured
      and imaged by scanning electron microscopy (SEM). At low magnification, 2
      different arrangements of collagen fibres were observed: leaf-like (human, pig,
      dog) and columnar (cow, sheep, rabbit, rat). The porcine collagen structure was
      the most similar to that of man. This arrangement was consistent from the radial
      to the upper zones. Under higher magnification at the surface of the leaves, the
      collagen was more randomly oriented, whereas the columns consisted of parallel
      collagen fibrils. The maximum thickness of cartilage did not correlate with the
      type of collagen arrangement but was correlated with the body weight of the
      species (r = 0.785). When using animal models for investigating human articular
      cartilage function or pathology, the differences in arrangement of collagen
      fibres in tibial plateau cartilage between laboratory animals should be
      considered especially if morphological evaluation is planned.

PMID- 9758135
TI  - Morphological and quantitative studies in the otic region of the neural tube in
      chick embryos suggest a neuroectodermal origin for the otic placode.
AB  - Careful histological observation of the development of the anlage of the inner
      ear in chicken embryos led us to question the traditional view of otic placode
      (OP) formation. First, morphological studies in the cephalic region carried out
      on stages preceding the appearance of the placodal epithelium revealed that the
      medial placodal cells are continuous temporally and spatially with cells
      belonging to the neural fold (NF). Second, both the formation of the basal lamina
      between the dorsal region of the neural tube (NT) and ectoderm and the pattern of
      formation of the neural crest present distinctive characteristics between otic
      levels and regions located anteriorly and posteriorly. Third, numerical
      comparisons of parameters for the NT and the OP between different levels of the
      rhombencephalon allowed us to assign a differential behaviour in the growth
      pattern of the otic region. These results indicated that the medial part of the
      OP is not derived from already independent ectoderm that increases in thickness
      under the influence of the NT (as previously accepted) but that it develops
      directly from the NFs. Although we do not exclude other possibilities, we propose
      that at least a proportion of the OP cells originate directly from cells
      committed to be neural crest. After this incorporation, basal laminal formation
      would delimit the NT from the OP without transition of the otic cells to
      ectoderm. This hypothesis would imply that part of the otic cells originate
      directly from neuroepithelial cells having a neuroectodermal (rather than the
      previously established ectodermal) origin.

PMID- 9758133
TI  - The role of laminins in basement membrane function.
AB  - Laminins are a family of multifunctional macromolecules, ubiquitous in basement
      membranes, and represent the most abundant structural noncollagenous
      glycoproteins of these highly specialised extracellular matrices. Their discovery
      started with the difficult task of isolating molecules produced by cultivated
      cells or extracted from tissues. The development of molecular biology techniques
      has facilitated and accelerated the identification and the characterisation of
      new laminin variants making it feasible to identify full-length polypeptides
      which have not been purified. Further, genetically engineered laminin fragments
      can be generated for studies of their structure-function relationship, permitting
      the demonstration that laminins are involved in multiple interactions with
      themselves, with other components of the basal lamina, and with cells. It endows
      laminins with a central role in the formation, the architecture, and the
      stability of basement membranes. In addition, laminins may both separate and
      connect different tissues, i.e. the parenchymal and the interstitial connective
      tissues. Laminins also provide adjacent cells with a mechanical scaffold and
      biological information either directly by interacting with cell surface
      components, or indirectly by trapping growth factors. In doing so they trigger
      and control cellular functions. Recently, the structural and biological diversity
      of the laminins has started to be elucidated by gene targeting and by the
      identification of laminin defects in acquired or inherited human diseases. The
      consequent phenotypes highlight the pivotal role of laminins in determining
      heterogeneity in basement membrane functions.

PMID- 9758137
TI  - A technique for establishing the identity of 'isolated' fossil hominin limb
      bones.
AB  - Associated skeletons, which are specimens preserving more than one body part from
      the same individual, are especially important for taxonomic and functional
      analyses. This study concentrates on the subset of associated skeletons which
      preserve the reciprocal surfaces of a joint. It uses laser scanning to explore
      whether the shapes of the reciprocal surfaces of a joint of an individual are
      significantly more congruent than the surfaces of randomly-matched pairings taken
      from the same species. Laser scanning was used to capture the distal articular
      surface of the left tibia of OH35 and the trochlear articular surface of the
      talus of OH8, both from Bed I, Olduvai Gorge, Tanzania. The degree of congruency
      between those articular surfaces was tested against the congruency of the
      talocrural joint of AL 288-1 (Australopithecus afarensis), and the congruency of
      both associated and randomly-matched talocrural joints of modern humans,
      chimpanzees and gorillas. The results suggest that OH35 and OH8 do not come from
      the same individual and may not come from the same species. Although this
      analysis leaves open the taxonomic affinity of OH35, it demonstrates the
      potential of laser scanning for capturing 3D data in palaeoanthropology. It also
      demonstrates the potential for using the relative congruency of reciprocal joint
      surfaces as a test of the likelihood that isolated limb bones are components of a
      single individual.

PMID- 9758136
TI  - Splenic adherent cells, stimulated in vitro, induce the reactive formation of
      lymphoid follicles and germinal centres in draining lymph nodes after
      subcutaneous transfusion into syngeneic mice.
AB  - The reactive formation of lymphoid follicles and germinal centres in lymph nodes,
      induced by subcutaneous transfer of in vitro activated splenic adherent cells
      into syngeneic mice, were studied. Adherent cells were obtained by incubating
      spleen cell suspensions for 24 h and activated by incubating for 1 h in the
      medium containing keyhole limpet haemocyanin (KLH) absorbed onto alumina. Some of
      the treated adherent cells were irradiated with 10 Gy x-rays, while others were
      either not stimulated or were stimulated with alumina-KLH but killed by repeated
      freezing and thawing. Examination of adherent cell smears immunostained with
      antibodies against, F4/80, Mac-1, Mac-2 and NLDC-145 indicated that many adherent
      cells displayed macrophage markers but few displayed the interdigitating cell
      marker. Animals transfused with KLH-treated adherent cells with or without
      irradiation showed a marked increase in the number of lymphoid follicles and
      germinal centres in draining lymph nodes, whereas those transfused with adherent
      cells which had not been KLH-treated or which had been killed after KLH treatment
      displayed no significant change in the number of follicles. These results were
      interpreted as indicating that following transfusion, antigen-activated adherent
      macrophages migrated into the draining lymph nodes and induced the reactive
      formation of lymphoid follicles and germinal centres outside preexisting
      follicles.

PMID- 9758138
TI  - Morphological study by an 'in vivo cryotechnique' of the shape of erythrocytes
      circulating in large blood vessels.
AB  - Changes in the shape of erythrocytes circulating in large blood vessels of mice
      were examined by our 'in vivo cryotechnique'. The abdominal aorta and inferior
      vena cava (IVC) were cut vertically with a precooled knife and simultaneously an
      isopentane-propane mixture (-193 degrees C) was poured over them for freezing.
      They were freeze-substituted in acetone containing 2% osmium tetroxide. Some
      specimens were embedded in Quetol-812, and thick or ultrathin sections were
      examined by light or transmission electron microscopy. Serial ultrathin sections
      were used to reconstruct 3-dimensional images of native erythrocytes. Others were
      transferred into t-butyl alcohol and freeze-dried for scanning electron
      microscopy. The tissue surfaces were sufficiently frozen to prevent large ice
      crystal formation, and erythrocyte shapes were also preserved. The shapes of
      circulating erythrocytes appeared to be varied in the abdominal aorta but typical
      biconcave discoid shapes were rarely observed. Conversely, erythrocytes were
      approximately biconcave discoid in shape in the IVC. Our in vivo cryotechnique
      was useful for clarifying the in vivo morphology of erythrocytes circulating in
      large blood vessels.

PMID- 9758139
TI  - Morphogenesis of Doublefoot (Dbf), a mouse mutant with polydactyly and
      craniofacial defects.
AB  - We report the morphogenesis of a new mouse mutant, Doublefoot (Dbf). The major
      phenotypic features involve the limb and craniofacial regions. There is
      polydactyly of all 4 limbs, with typically 6-8 digits per limb. All of the digits
      are triphalangeal; some show bifurcations and some are not attached to the
      carpus/tarsus. The carpus and tarsus are broader than normal, and their elements
      are partially fused. There are also tibial defects. Mutant embryos show a
      diencephalic bulge on d 10.0, with older animals exhibiting broadened and bulbous
      skulls sometimes with an additional midline skeletal element, shortened snouts
      and bulging eyes. Homozygotes, which do not survive beyond d 15, show midline
      facial clefting. In this study of the embryonic and fetal development of Dbf
      animals, we focus on the morphogenesis of the limbs and head, and discuss the
      possible molecular developmental mechanisms.

PMID- 9758140
TI  - Morphological and functional evidence, and clinical importance, of vascular
      anastomoses in the latissimus dorsi muscle of the sheep.
AB  - Mobilisation of the latissimus dorsi muscle as a functional graft necessarily
      involves division of perforating arteries that enter the distal portion of the
      muscle, rendering it vulnerable to ischaemic damage when the muscle is stimulated
      electrically. Using a fluorescent microsphere technique we showed that the blood
      flow contributed by the thoracodorsal artery decreases in a proximal-to-distal
      direction, and that of the perforating arteries in a distal-to-proximal
      direction, but for neither does the flow decline to zero. This is consistent with
      earlier reports of anastomotic connections between the 2 arterial territories. We
      went on to use fluorescence microscopy to demonstrate the existence of these
      vascular anastomoses, the first such evidence obtained under physiological
      conditions of pressure and flow. In clinical applications, the existence of
      anastomotic connections offers the prospect of maintaining flow to the distal
      part of the grafted muscle without the delays inherent in neovascularisation
      procedures.

PMID- 9758141
TI  - Anatomy of the pig heart: comparisons with normal human cardiac structure.
AB  - Transgenic technology has potentially solved many of the immunological
      difficulties of using pig organs to support life in the human recipient.
      Nevertheless, other problems still remain. Knowledge of cardiac anatomy of the
      pig (Sus scrofa) is limited despite the general acceptance in the literature that
      it is similar to that of man. A qualitative analysis of porcine and human cardiac
      anatomy was achieved by gross examination and dissection of hearts with
      macrophotography. The porcine organ had a classic 'Valentine heart' shape,
      reflecting its location within the thorax and to the orientation of the pig's
      body (unguligrade stance). The human heart, in contrast, was trapezoidal in
      silhouette, reflecting man's orthograde posture. The morphologically right atrium
      of the pig was characterised by the tubular shape of its appendage (a feature
      observed on the left in the human heart). The porcine superior and inferior caval
      veins opened into the atrium at right angles to one another, whereas in man the
      orifices were directly in line. A prominent left azygous vein (comparable to the
      much reduced left superior caval or oblique vein in man) entered on the left side
      of the pig heart and drained via the coronary sinus. The porcine left atrium
      received only 2 pulmonary veins, whereas 4 orifices were generally observed in
      man. The sweep between the inlet and outlet components of the porcine right
      ventricle was less marked than in man, and a prominent muscular moderator band
      was situated in a much higher position within the porcine right ventricle
      compared with that of man. The apical components of both porcine ventricles
      possessed very coarse trabeculations, much broader than those observed in the
      human ventricles. In general, aortic-mitral fibrous continuity was reduced in the
      outlet component of the porcine left ventricle, with approximately two-thirds of
      the aortic valve being supported by left ventricular musculature. Several
      potentially significant differences exist between porcine and human hearts. It is
      important that these differences are considered as the arguments continue
      concerning the use of transgenic pig hearts for xenotransplantation.

PMID- 9758142
TI  - A polydactylous human foot with 'double-dorsal' toes.
AB  - A human polydactylous left foot with 9 toes, amputated from an 11-mo-old child,
      was examined by x-ray and magnetic resonance imaging and by gross dissection to
      identify the digits. The normal sequence of toes from medial to lateral is 1, 2,
      3, 4, 5. Examination of the morphology of tendons and muscles suggested the toe
      sequence was 1, 2, 3/4, ?5, 2, 3/4, 3/4, 5. The 2 toes in the sequence that are
      underlined were displaced dorsally and were found to have 2 extensor tendons, no
      flexor tendons and nails that were conical and situated at their tips. These toes
      resembled those described as 'double-dorsal' and which develop in paws of mice in
      which a gene normally expressed ventrally is functionally inactivated (Loomis et
      al. 1996). Specification of toe formation occurs in leg buds early in embryonic
      development and later there is rotation of the limb so that the anterior
      (rostral) part comes to lie medially, i.e. the hallux which was anterior
      (rostral) now is on the inner (medial) side of the foot. A disruption in the
      patterning of this foot in both anteroposterior (rostral-caudal) and dorsoventral
      axes during development could be responsible.

PMID- 9758143
TI  - The morphological basis of increased stiffness of rabbit tibialis anterior
      muscles during surgical limb-lengthening.
AB  - When the tibialis anterior muscle of the rabbit is progressively stretched during
      surgical limb distraction, the muscle fibres lengthen by addition of new serial
      sarcomeres, provided that stretch is carried out at an appropriate rate. However,
      in spite of the apparent adaptation to the new functional length, range of joint
      movement is greatly decreased. In this study we have first, made measurements of
      the passive tension developed by distracted muscles over the range of joint
      movement and secondly made quantitative measurements of endomysial and perimysial
      connective tissue content. It was found that at all ankle joint angles greater
      than 90 degrees, the passive tension developed by the distracted muscles was
      greater than both contralateral and sham-operated controls. Image analysis showed
      that the ratio of collagen to contractile material was increased in distracted
      muscles compared with muscles from sham-operated controls, due to increased
      deposition of collagen type III. Scanning electron microscopy showed the presence
      of a dense perimysial weave surrounding the distracted muscle fibres. These
      quantitative and qualitative changes in the connective tissue component could
      account for the increased stiffness demonstrated by the physiological
      measurements. It would seem that in distracted muscle the connective tissue
      element adapts less readily than the contractile component, with prolonged
      stretch leading to damage to the perimysial and endomysial network, with
      subsequent fibrosis and loss of muscle compliance. Such changes could help
      explain the loss of range of movement noted in the distracted limbs of patients
      undergoing surgical limb-lengthening and in other conditions that result in
      muscle contractures.

PMID- 9758144
TI  - A comparison of four in vivo methods of measuring tibial torsion.
AB  - Tibial torsion, twisting of the tibia about its longitudinal axis, varies during
      development and early childhood. Knowledge of the normal range of tibial torsion
      at various ages and its accurate clinical measurement is important in the
      assessment of the extent of a torsional deformity. To evaluate tibial torsion a
      reliable technique for its measurement in vivo is therefore required. The aim of
      this study was to determine which of 4 existing in vivo methods of measuring
      tibial torsion was the most accurate and had the highest repeatability, by
      comparing them with direct measurement of the tibia. A wide range of mean values
      for tibial torsion was observed, using the various techniques, with none of the
      indirect techniques employed having a strong correlation with direct measurement
      of tibial torsion. The repeatability of the indirect techniques was observed to
      be low both in cadavers (n = 4) and the living (n = 3). Since none of the in vivo
      techniques appear to measure true tibial torsion or be of a reasonable
      repeatability, alternative easy to use and inexpensive methods need to be
      developed. Accurate clinical measurement of tibial torsion is important in the
      assessment of the extent of a torsional deformity. It is recommended that data
      gained using the methods reviewed here are interpreted with caution.

PMID- 9758145
TI  - Metatarsal growth during the second trimester: a predictor of gestational age?
AB  - Metatarsal growth was studied in 780 human fetal metatarsal bones, crown-rump
      length ranging from 120 to 260 mm and gestational age ranging from 14 to 23 wk
      postconception. Total length, diaphyseal length and diameter were measured and
      statistical analysis performed. Means and standard deviations for each
      measurement were calculated at 1 wk intervals. These data were correlated with
      crown-rump length and gestational age and an equation was constructed in an
      attempt to predict gestational age.

PMID- 9758146
TI  - Expression of the mRNA for the beta 2 subunit of the voltage-dependent sodium
      channel in rat CNS.
AB  - Expression of the voltage-dependent sodium channel has been analysed in adult rat
      central nervous system by Northern blotting and in situ hybridization. Northern
      blots showed that all the territories studied express beta 2 transcripts, albeit
      with widely varying levels (with cerebellum >> hippocampus > brain > brainstem >
      spinal cord). In situ hybridization confirmed that in these structures, all the
      neuronal cell bodies contain beta 2 mRNA; expression was particularly high in the
      granule cells of the cerebellum, in both pyramidal cell layer and dentate gyrus
      in the hippocampus, and in spinal cord motor neurons. Northern blots also showed
      that RNA extracted from optic nerve and cultured cortical astrocytes contained
      beta 2 mRNA, while it was totally absent from sciatic nerve. In situ
      hybridization evidenced the presence of a numerous population of beta 2-positive
      cells in cerebellum white matter, spinal cord white matter, and in corpus
      callosum, where frontal sections showed labelled cells arranged in the chain-like
      or row pattern typical of interfascicular oligodendrocytes. Combination of
      antiglial fibrillary acid protein (GFAP) immunofluorescent histochemistry with
      detection of beta 2 mRNA evidenced that expression of the transcripts was indeed
      restricted to GFAP-negative cells in white matter.

PMID- 9758147
TI  - Reduction of advanced glycation end-product (AGE) levels in nervous tissue
      proteins of diabetic Lewis rats following islet transplants is related to
      different durations of poor metabolic control.
AB  - Advanced glycation end-products (AGEs) are irreversible compounds which, by
      abnormally accumulating over proteins as a consequence of diabetic
      hyperglycaemia, can damage tissues and thus contribute to the pathogenesis of
      diabetic complications. This study was performed to evaluate whether restoration
      of euglycaemia by islet transplantation modifies AGE accumulation in central and
      peripheral nervous tissue proteins and, as a comparison, in proteins from a non
      nervous tissue. Two groups of streptozotocin diabetic inbred Lewis rats with 4
      (T1) or 8 (T2) months disease duration were grafted into the liver via the portal
      vein with 1200-1500 islets freshly isolated from normal Lewis rats. Transplanted
      rats, age-matched control and diabetic rats studied in parallel, were followed
      for a further 4-month period. At study conclusion, glycaemia, glycated
      haemoglobin and body weight were measured in all animals, and an oral glucose
      tolerance test (OGTT) performed in transplanted rats. AGE levels in cerebral
      cortex, spinal cord, sciatic nerve proteins and tail tendon collagen were
      measured by enzyme-linked immunosorbent assay (ELISA). Transplanted animal OGTTs
      were within normal limits, as were glycaemia and glycated haemoglobin. Diabetic
      animal AGEs were significantly higher than those of control animals. Protein AGE
      values were reduced in many transplanted animals compared to diabetic animals,
      reaching statistical significance in spinal cord (P < 0.05), sciatic nerve (P <
      0.02) and tail tendon collagen (P < 0.05) of T1 animals. Thus, return to
      euglycaemia following islet transplantation after 4 months of diabetes with poor
      metabolic control reduces AGE accumulation rate in the protein fractions of the
      mixed and purely peripheral nervous tissues (spinal cord and sciatic nerve,
      respectively). However, after a double duration of bad metabolic control, a
      statistically significant AGE reduction has not been achieved in any of the
      tissues, suggesting the importance of an early therapeutic intervention to
      prevent the possibly pathological accumulation of AGEs in nervous and other
      proteins.

PMID- 9758148
TI  - Beta-adrenergic and fibroblast growth factor receptors induce neuronal process
      outgrowth through different mechanisms.
AB  - The mechanisms that initiate and direct neuronal process formation remain poorly
      understood. We have recently described a neuronal progenitor cell line, AS583
      8.E4.22 (AS583-8) which undergoes neurite formation in response to beta2
      adrenergic and basic fibroblast growth factor (bFGF) receptor activation [Kwon,
      J.H. et al., (1996) Eur. J. Neurosci., 8, 2042-2055]. In the present study, a
      comparison of these responses revealed that isoproterenol (ISO), a beta
      adrenergic receptor agonist, induces multiple, highly branched processes within
      30 min while bFGF induces fewer, unbranched processes within 24 h. In contrast to
      the ISO response, bFGF induces mitogen-activated protein kinase activation and c
      fos expression in the cell line and results in neurite outgrowth that is
      dependent on new mRNA and protein synthesis. Two-dimensional isoelectric focusing
      sodium dodecyl sulphate-polyacrylamide gel electrophoresis of cytoskeletal
      preparations revealed different patterns following ISO vs. bFGF exposure
      suggesting selective changes in protein expression and/or post-translational
      modifications. Immunoblot analysis of these preparations for beta-tubulin,
      tyrosinated alpha-tubulin and acetylated alpha-tubulin also revealed different
      patterns following each type of treatment. Follow-up confocal microscopy revealed
      that following ISO, the distribution of tyrosinated tubulin extends to the distal
      ends of processes whereas acetylated alpha-tubulin is diminished within distal
      ends. This pattern has been reported to be associated with enhanced microtubule
      dynamics, a state in which process outgrowth is facilitated. In contrast,
      following bFGF treatment the distributions of tyrosinated and acetylated alpha
      tubulin were identical, a state associated with a diminution of microtubule
      dynamics. These results, a different time course of neurite formation, dependency
      on new gene expression and differential expression and cellular distribution of
      major cytoskeleton proteins suggest that neurite outgrowth induced by ISO vs.
      bFGF is mediated by two distinct intracellular effector mechanisms in AS583-8
      cells. In addition, studies, using the differential distribution of post
      translational modified alpha-tubulins in neurites of primary neuronal cultures as
      marker for the two distinct processes of neurite formation suggest, that similar
      mechanisms are present in vivo. Therefore, the AS583-8 cell line provides a
      useful model to study these signalling mechanisms that couple neurotransmitter
      and growth factor receptor activation to the cytoskeletal changes that mediate
      neurite formation.

PMID- 9758149
TI  - Electrophysiological and neurochemical study of the rat geniculo-cortical
      pathway. Evidence for glutamatergic neurotransmission.
AB  - The projection from the dorsal lateral geniculate nucleus to the primary visual
      cortex of the rat was studied electrophysiologically. Electrical stimulation of
      the dorsal lateral geniculate nucleus and the optic tract produced three types of
      responses on neurons of area 17: excitation followed by inhibition, excitation
      and inhibition. These results extend and confirm, in adult rats, previous studies
      done in rat geniculate-visual cortex cocultures preparations in vitro. The role
      of glutamate in the neurotransmission of the rat geniculo-cortical pathway was
      also investigated. In a first set of experiments, the effects of kynurenate, an
      antagonist of glutamate receptors, on visual cortex neurons with a monosynaptic
      excitatory response to dorsal lateral geniculate nucleus stimulation were
      studied. Microiontophoresis of kynurenate in area 17 neurons selectively
      suppressed the excitatory response to dorsal lateral geniculate nucleus and optic
      tract stimulation. In a second set of experiments, the effects of electrical
      stimulation of the dorsal lateral geniculate nucleus and the optic tract on the
      release of amino acids in the rat visual cortex in vivo were studied. Using the
      push-pull method, we perfused a discrete region of the visual cortex with
      artificial cerebrospinal fluid (CSF), and the amino acid content of the
      perfusates was analysed by high performance liquid chromatography (HPLC).
      Stimulation of either the dorsal lateral geniculate nucleus or the optic tract
      significantly increased glutamate release in area 17. The rest of the amino acids
      studied did not show significant changes. The results provide evidence for the
      participation of glutamate in the neurotransmission of the geniculo-cortical
      pathway in the rat.

PMID- 9758150
TI  - Regional brain variations of cytochrome oxidase activity and motor coordination
      in hot-foot mutant mice.
AB  - Hot-foot mutant mice are characterized by defective arborization of Purkinje cell
      dendrites, resulting in ataxia of gait and deficits of equilibrium. Regional
      brain variations of cytochrome oxidase (CO) activity were analysed for the
      purpose of identifying those brain regions with abnormal metabolic activity as a
      secondary consequence to the cerebellar alteration. In addition, the possible
      relation between CO activity and motor deficits was evaluated. By comparison to
      normal littermate controls of the same background strain, hot-foot mutants had
      higher CO activity in the molecular layer of the cerebellum, the ventrolateral
      and midline thalamic nuclei, as well as in the frontal eye field. There was no
      other alteration of CO activity in the hot-foot brain. No linear correlation was
      discerned between CO activity in the molecular layer of the cerebellum and the
      ventrolateral and midline nuclei on one hand, and motor coordination performance
      on the other. These results indicate regionally selective abnormalities of
      metabolic activity in a cerebellar mutant with defective dendritic arborization
      of the Purkinje cell.

PMID- 9758152
TI  - Increase in meso-prefrontal dopaminergic activity after stimulation of CB1
      receptors by cannabinoids.
AB  - The intravenous administration of the psychoactive constituent of marijuana,
      delta9-tetrahydrocannabinol (delta9-THC) (62.5-1000 microg/kg), and the synthetic
      cannabinoid agonist WIN 55212,2 (WIN) (62.5-500 microg/kg), produced a dose
      related increase in the firing rate and burst firing in the majority of
      antidromically identified meso-prefrontal dopaminergic neurons. In a restricted
      number of neurons (n=4), WIN administration did not increase firing rate but
      produced an increment of bursting activity. These effects of the cannabinoids
      were reversed by the intravenous administration of SR 141716 A, a selective
      cannabinoid antagonist (1 mg/kg), per se ineffective to modify the electrical
      activity of dopaminergic neurons. The results indicate that stimulation of
      cannabinoid CB1 receptors produces an activation of meso-prefrontal dopaminergic
      transmission. Considering that supranormal stimulation of D1 dopamine receptors
      in the prefrontal cortex has been shown to impair working memory, the present
      results suggest that the negative effects of cannabinoids on cognitive processes
      might be related to the activation of dopaminergic transmission in the prefrontal
      cortex.

PMID- 9758153
TI  - Neuronal coding of interaural transient envelope disparities.
AB  - Onsets are salient and important transient (i.e. dynamic) features of acoustic
      signals, and evoke vigorous responses from most auditory neurons, but
      paradoxically these onset responses have most often been analysed with respect to
      steady-state stimulus features, e.g. the sound pressure level (SPL). In nearly
      all studies concerned with the coding of differences in SPL at the two ears
      (interaural level differences; ILDs), which provide a major cue for the azimuthal
      location of high frequency sound sources, interaural onset disparities were
      covaried with ILD, but the possibly confounding effects of this covariation on
      neuronal responses have been entirely neglected. Therefore, dichotic stimulus
      paradigms were designed here in which onset and steady-state features were varied
      independently. Responses were recorded from single neurons in the inferior
      colliculus of rats, anaesthetized with pentobarbital and xylazine. It is
      demonstrated that onset responses, or the onset response components of neurons
      with more complex temporal response patterns, are dependent on the binaural
      combination of dynamic envelope features associated with conventional ILD
      stimulus paradigms, but not on the binaural combination of steady-state SPLs
      reached after the onset. In contrast, late or sustained response components
      appear more sensitive to the binaural combination of steady-state SPLs. These
      data stress the general necessity for a separate analysis of onset and late
      response components, with respect to different stimulus features, and suggest a
      need for re-evaluation of existing studies on ILD coding. The sensitivity of
      onset responses to the binaural combination of envelope transients, rather than
      to steady-state ILD, is in line with their sensitivity to other interaural
      envelope disparities, created by stationary or moving sounds.

PMID- 9758151
TI  - MuSC, a novel member of the immunoglobulin superfamily, is expressed in neurons
      of a subset of cranial sensory ganglia in the mouse embryo.
AB  - In contrast to the spinal sensory ganglia which reiterate a basic organizational
      and functional unit, each cranial ganglion mediates a distinct sensory modality
      and exhibits a characteristic pattern of peripheral and central neuronal
      connectivity. Molecules responsible for establishment and maintenance of the
      cranial ganglion-specific networks are not known. Our hamster monoclonal antibody
      802C11 strongly stained neurons and their processes of the VIIIth cranial
      ganglion (hearing and equilibrium), but not of the Vth cranial (somatosensory) or
      spinal ganglia in the mouse embryo. The cellular staining pattern of positive
      neurons suggested that the antigen was associated with the cell membrane, and
      biochemical analyses of the antigen from adult mouse brain showed the antigen to
      be a glycosylated intrinsic membrane protein of approximately 100 kDa. The
      antigen was purified, and based on the partial amino acid sequences, its entire
      cDNA was cloned. A bacterially expressed polypeptide encoded by the cDNA was
      recognized by the antibody. The deduced amino acid sequence revealed that the
      antigen belongs to the immunoglobulin superfamily with a significant homology
      (73.5% identity) to chicken SC1 protein. Chicken SC1 has been shown to be a cell
      cell adhesion molecule in vitro with a proposed role in neurite extension of
      spinal motor neurons. These results suggest that our murine SC1-related protein
      (MuSC) is involved in the pathfinding and/or fasciculation of specific cranial
      sensory nerve fibres.

PMID- 9758154
TI  - Antagonists for group I mGluRs attenuate excitotoxic neuronal death in cortical
      cultures.
AB  - Activation of ion channel-linked glutamate receptors, especially N-methyl-D
      aspartate (NMDA) receptors, mediates the excitotoxic effects of glutamate upon
      central neurons. We examined the hypothesis that activation of group I
      metabotropic glutamate receptors (mGluRs) would increase NMDA receptor-mediated
      cortical neuronal death. Addition of the selective group I mGluR agonists,
      dihydroxyphenylglycine (DHPG) or trans-azetidine-2,4-dicarboxylic acid (t-ADA)
      potentiated NMDA-induced neuronal death, and application of the group I mGluR
      selective antagonist, aminoindan-1,5-dicarboxylic acid (AIDA), as well as the non
      selective antagonists methyl-4-carboxyphenylglycine (MCPG) or 4
      carboxyphenylglycine (4CPG) reduced NMDA- and kainate-induced neuronal death in
      murine cortical cultures. The pro-excitotoxic effect of group I mGluR activation
      may be mediated largely by enhancement of glutamate release, as DHPG potentiated
      high potassium-stimulated glutamate release, and the protective effects of both
      AIDA and MCPG were abolished when NMDA and alpha-amino-3-hydroxy-5-methyl-4
      isoxazole proprionic acid (AMPA) receptors were blocked immediately after toxic
      NMDA receptor overstimulation. The present data support the possibility that
      antagonizing group I mGluRs may be a useful strategy for attenuating excitotoxic
      neuronal death in certain disease states.

PMID- 9758155
TI  - Co-localized neuropeptide Y and GABA have complementary presynaptic effects on
      sensory synaptic transmission.
AB  - We have examined the morphological relationship of neuropeptide Y (NPY) and
      GABAergic neurons in the lamprey spinal cord, and the physiological effects of
      NPY and GABA(B) receptor agonists on afferent synaptic transmission. NPY
      containing fibres and cell bodies were identified in the dorsal root entry zone.
      NPY immunoreactive (-ir) fibres made close appositions with primary afferent
      axons. Co-localization of NPY and GABA-ir was found in the dorsal horn and dorsal
      column. Fifty-two per cent of NPY-ir profiles showed immunoreactivity to GABA at
      the ultrastructural level. Electron microscopic analysis showed that NPY
      immunoreactivity was present throughout the axoplasm, including over dense core
      vesicles, whereas GABA-immunoreactivity was mainly found over small synaptic
      vesicles. Synthetic lamprey NPY, and the related peptide, peptide YY, reduced the
      amplitude of monosynaptic afferent EPSPs in spinobulbar neurons. NPY had no
      significant effect on the postsynaptic input resistance or membrane potential,
      the electrical component of the synaptic potential, or the response to glutamate,
      but it could reduce the duration of presynaptic action potentials, suggesting
      that it was acting presynaptically. NPY also reduced the excitability of the
      spinobulbar neurons, suggesting at least one postsynaptic effect. Because NPY and
      GABA colocalize, we compared the effects of NPY and the GABA(B) agonist baclofen.
      Both presynaptically reduced EPSP amplitudes, baclofen having a larger effect and
      a faster onset and recovery than NPY. The GABA(B) antagonist phaclofen reduced
      the effect of baclofen, but not that of NPY. We conclude that NPY and GABA are
      colocalized in terminals in the dorsal spinal cord of the lamprey, and that they
      have complementary actions in modulating sensory inputs.

PMID- 9758156
TI  - Network bursting by organotypic spinal slice cultures in the presence of
      bicuculline and/or strychnine is developmentally regulated.
AB  - Organotypic cocultures of dorsal root ganglia and spinal cord from embryonic rats
      provides direct access to spinal interneurons in a culture system in which the
      cytoarchitectural organization of the spinal cord slice is maintained. This
      preparation was used to investigate the possible induction of rhythmic behaviour
      at different times of development in vitro. Spontaneous rhythmic bursts induced
      by coapplication of strychnine (1 microM) and bicuculline (20 microM) were
      observed with patch-clamp recordings from ventral interneurons. Ventral horn
      interneurons consistently developed a very regular pattern of activity which was
      superimposed on a background of sustained synaptic activity. The pattern of the
      spontaneous bursting following application of strychnine and bicuculline showed a
      developmentally regulated difference in frequency between two distinct stages of
      in vitro development.

PMID- 9758157
TI  - Neuroactive steroids induce GABA(A) receptor-mediated depolarizing postsynaptic
      potentials in hippocampal CA1 pyramidal cells of the rat.
AB  - Intracellular recordings were performed in area CA1 pyramidal cells of rat
      hippocampal slices to determine the effects of certain steroids on inhibitory
      postsynaptic potentials/currents (IPSP/Cs) mediated by GABA(A) receptors.
      Following application of the steroids 5alpha-pregnan-3alpha,21-diol-20-one
      (5alpha-THDOC), alphaxalone and 5beta-pregnan-3alpha-ol-20-one (pregnanolone)
      hyperpolarizing PSPs developed into biphasic responses consisting of an early
      hyperpolarizing and a late depolarizing PSP sequence. Steroid-induced
      depolarizing PSPs could be elicited in the presence of antagonists to non-NMDA,
      NMDA, and GABA(B) receptors, indicating that these receptor types do not
      contribute significantly to the initiation of these responses. Depolarizing PSPs
      were completely blocked by both GABA(A) receptor antagonists bicuculline and t
      butylbicyclophosphorothionat (TBPS) providing evidence for their mediation by
      GABA(A) receptors. The reversal potential of steroid-induced late inward PSCs,
      measured in single-electrode voltage clamp, was -29.9+/-5.3 mV, whereas the early
      outward current, which corresponded to the early hyperpolarizing component of
      PSPs, reversed at -68.2+/-1.5 mV. Depolarizing PSPs and late inward PSCs were
      sensitive to reduction of extracellular [HCO3-] and block of carbonic anhydrase
      by application of acetazolamide. The results suggest that certain neuroactive
      steroids can induce GABA(A) receptor-mediated depolarizing PSPs, which are
      dependent on HCO3-.

PMID- 9758159
TI  - Rhythmic variation in beta1-adrenergic receptor mRNA levels in the rat pineal
      gland: circadian and developmental regulation.
AB  - In the rat pineal gland noradrenaline is released in large quantities from
      sympathetic nerve endings at the onset of darkness, thereby driving rhythmic
      melatonin synthesis with elevated levels at night-time. Upon release,
      noradrenaline interacts with postsynaptic beta1-adrenergic receptors to activate
      the cyclic AMP signalling pathway. Well characterized third messengers of this
      signalling cascade affect cyclic AMP-inducible genes that are crucially involved
      in initiation, maintenance and termination of hormone production. Among these
      third messengers are CREB (cyclic AMP responsive element binding protein) as an
      activating and ICER (inducible cyclic AMP early repressor) as an inhibitory
      transcription factor. Because a cyclic AMP-inducible promoter element is present
      on the beta1-adrenergic receptor gene, the expression of the receptor itself may
      be under control of the cyclic AMP-signalling pathway. By in situ hybridization,
      Northern blot analysis and RT-PCR we demonstrate a day/night rhythm in beta1
      adrenergic receptor mRNA in the rat pineal gland with elevated levels during the
      dark period. As this rhythm persists, under constant darkness but is abolished
      upon removal of the sympathetic innervation, it is truly circadian. A marked
      day/night difference in the levels of beta1-adrenergic receptor mRNA becomes
      evident only after postnatal day 10, coinciding with the appearance of a
      functional cyclic AMP signalling pathway in the rat pineal gland. Furthermore,
      targeting ICER expression by transfection of pinealocytes with an antisense ICER
      construct, clearly indicates that the levels of the beta1-adrenergic receptor
      mRNA are regulated by the cyclic AMP-signalling pathway in a feedback mechanism.

PMID- 9758160
TI  - Molecular and functional adaptation of the GABA(A) receptor complex during
      pregnancy and after delivery in the rat brain.
AB  - The abundance of gamma-aminobutyric acid receptor type A (GABAA receptor) subunit
      mRNAs and polypeptides as well as muscimol-stimulated 36Cl- uptake were measured
      in rat cerebral cortex or hippocampus at various times during pregnancy and after
      delivery. RNase protection assays revealed that the amount of the gamma2L subunit
      mRNA decreased progressively during pregnancy, in the cerebral cortex and
      hippocampus, and then returned to control values around the time of delivery. A
      similar pattern was observed for the alpha5 subunit mRNA in the cerebral cortex,
      whereas no significant changes were apparent for alpha1, alpha2, alpha3, alpha4,
      beta1, beta2, beta3 and gamma2S subunit mRNAs. The amounts of gamma2 and alpha1
      proteins in the cerebral cortex were measured by immunoblot analysis; whereas the
      abundance of gamma2 protein decreased during pregnancy, no change was detected in
      the amount of alpha1 protein. Evaluation for functional significance of the down
      regulated gamma2 and alpha5 subunit was made by determining the GABAA receptor
      function assessed by measurement of muscimol-stimulated 36Cl- uptake in cerebral
      cortical membrane vesicles. Muscimol-induced 36Cl- uptake was markedly reduced
      during of pregnancy compared with rats in oestrus. At this same time, the
      potentiating effects of diazepam and allopregnanolone on muscimol stimulation of
      36Cl- uptake also were reduced. In contrast, the effects of muscimol,
      allopregnanolone and diazepam were significantly increased, relative to animals
      in oestrus, after delivery.

PMID- 9758158
TI  - Endogenous ACh enhances striatal NMDA-responses via M1-like muscarinic receptors
      and PKC activation.
AB  - Cortical glutamatergic fibres and cholinergic inputs arising from large aspiny
      interneurons converge on striatal spiny neurons and play a major role in the
      control of motor activity. We have investigated the interaction between
      excitatory amino acids and acetylcholine (ACh) on striatal spiny neurons by
      utilizing intracellular recordings, both in current- and in voltage-clamp mode in
      rat brain slices. Muscarine (0.3-10 microM) produced a reversible and dose
      dependent increase in the membrane depolarizations/inward currents induced by
      brief applications of N-methyl-D-aspartate (NMDA), while it did not affect the
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-induced responses.
      These concentrations of muscarine did not alter the membrane potential and the
      current-voltage relationship of the recorded cells. Neostigmine (0.3-10 microM),
      an ACh-esterase inhibitor, mimicked this facilitatory effect. The facilitatory
      effects of muscarine and neostigmine were antagonized either by scopolamine (3
      microM) or by pirenzepine (10-100 nM), an antagonist of M1-like muscarinic
      receptors, but not by methoctramine (300 nM), an antagonist of M2-like muscarinic
      receptor. Accordingly, these facilitatory effects were mimicked by McN-A-343 (1
      10 microM), an agonist of M1-like muscarinic receptors, but not by oxotremorine
      (300 nM), an agonist of M2-like receptors. Tetrodotoxin (TTX) did not block the
      facilitatory effect produced by the activation of muscarinic receptors suggesting
      that this effect is postsynaptically mediated. The action of neostigmine was
      prevented either by the intracellular calcium (Ca2+) chelator BAPTA (200 mM) or
      by preincubating the slices with inhibitors of protein kinase C (PKC)
      (staurosporine 100 nM or calphostin C 1 microM). McN-A-343 did not alter the
      excitatory post synaptic potentials (EPSPs) evoked by corticostriatal stimulation
      in the presence of physiological concentration of magnesium (Mg2+ 1.2 mM), while
      it enhanced the duration of these EPSPs recorded in the absence of external
      magnesium. Our data show that endogenous striatal ACh exerts a positive
      modulatory action on NMDA responses via M1-like muscarinic receptors and PKC
      activation.

PMID- 9758161
TI  - Survival motor neuron (SMN) protein in rat is expressed as different molecular
      forms and is developmentally regulated.
AB  - Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by
      a progressive degeneration of motoneurons in spinal cord and brainstem. The
      telomeric copy of a duplicated gene termed survival motor neuron (smn), which
      maps to chromosome 5q13, has been found to be deleted in most patients. The
      encoded gene product is a novel protein which recently has been shown to
      accumulate in specific nuclear organelles (gemini of coiled bodies, GEMS), and to
      play a part in the formation of the spliceosome complex. We have cloned and
      sequenced the rat smn cDNA. Antibodies generated against an N-terminus peptide
      recognized a main protein of 32 kDa in immunoblots of rat embryonic tissue
      extracts. Minor bands of 35 kDa, 45 kDa and, in perinatal muscle, of 24 kDa were
      also specifically detected, indicating that SMN is expressed as different
      molecular forms. Subcellular fractionation indicated that the 32 kDa form is
      mainly soluble, while the 35 kDa and 45 kDa products segregate to the microsomal
      mitochondrial fraction. SMN protein is highly regulated during development:
      expression is high in embryonic tissues (central nervous system, muscle, lung and
      liver), and then progressively decreases to very low levels in most tissues of
      the adult. The demonstration of different molecular forms of SMN along with its
      developmental regulation may help to understand the contribution of this protein
      in the appearance of SMA phenotype.

PMID- 9758162
TI  - Evidence for a GABAergic projection from the central nucleus of the amygdala to
      the brainstem of the macaque monkey: a combined retrograde tracing and in situ
      hybridization study.
AB  - The central nucleus of the amygdala is interconnected with a variety of visceral
      and autonomic nuclei of the brainstem. These include the parabrachial nucleus,
      the nucleus of the solitary tract, the nucleus ambiguus and the dorsal motor
      nucleus of the vagus. Despite repeated attempts, neurochemical characterization
      of the major subcortical connections of the central nucleus has not yet been
      accomplished. Based on earlier immunohistochemical and in situ hybridization
      evidence indicating the presence of numerous GABAergic neurons in the macaque
      monkey central nucleus, we predicted that a sizeable portion of the descending
      projections may be GABAergic. We tested this hypothesis using a novel double
      labelling method with gold conjugated WGA-apoHRP as a retrograde tracer and in
      situ hybridization for detecting the mRNA that encodes the enzyme glutamic acid
      decarboxylase (GAD67) as a marker for GABAergic cells. Following WGA-apoHRP-gold
      injections into the brainstem, a large number of retrogradely labelled cells was
      observed in the medial and lateral divisions of the central nucleus. Of the
      retrogradely labelled cells observed in the medial division of the central
      nucleus, approximately half were double-labelled for GAD67 mRNA; about 30% double
      labelling was observed in the lateral division. These data support the view that
      a sizeable component of the central nucleus projection to the brainstem is
      GABAergic.

PMID- 9758164
TI  - Excitatory convergence of Y and non-Y channels onto single neurons in the
      anterior ectosylvian visual area of the cat.
AB  - Numerous functional and hodological studies of the anterior ectosylvian visual
      area (AEV) of the cerebral cortex of the cat suggest that this area plays an
      important role in processing information about visual motion. In the present
      study, in cats with selective conduction block of Y fibres in one optic nerve, we
      have examined the extent of the excitatory convergence of Y (presumed 'motion
      channel') and non-Y information channels on single neurons in AEV, as well as the
      contribution of the Y channel to the receptive field properties of AEV neurons.
      While in normal cats all neurons recorded from AEV were binocular, i.e. could be
      photically activated via either eye, in cats with selective conduction block of Y
      fibres in one optic nerve, a significant proportion (about 15%) of AEV cells
      could be photically activated only via the normal eye. In comparison to those in
      normal cats, the peak discharge rates of AEV neurons in the Y-blocked cats were
      drastically reduced not only when photic stimuli were presented via the Y-blocked
      eye, but also when they were presented via the normal eye. Selective block of Y
      input also resulted in a significant shift in velocity preferences towards the
      lower velocities. However, the direction selectivity indices of AEV neurons were
      not affected by selective Y block. Thus: (i) the responses of AEV neurons to a
      high velocity of motion are dependent on the integrity of the Y input; (ii) the
      'spontaneous' (i.e. not photically evoked) discharges of Y retinal ganglion cells
      exert a facilitatory influence on the responses of AEV cells to photic stimuli;
      (iii) although the responses of AEV neurons are dominated by the Y inputs, AEV
      neurons also receive significant non-Y excitatory inputs; and (iv) the strong
      direction selectivity revealed in most AEV neurons does not dependent on the
      integrity of Y input.

PMID- 9758163
TI  - Evidence for functional native NMDA receptors activated by glycine or D-serine
      alone in the absence of glutamatergic coagonist.
AB  - In this study we have examined the effects of N-methyl-D-aspartate (NMDA)
      receptor activation on the release of cholecystokinin and somatostatin from rat
      neocortical nerve endings. The release of cholecystokinin-like immunoreactivity
      (CCK-LI) and of somatostatin-like immunoreactivity (SRIF-LI) elicited by 12 mM K+
      from superfused synaptosomes, but not the spontaneous release, was increased by
      NMDA in a concentration-dependent manner. The effects of NMDA could be prevented
      by antagonists selective for the glutamate recognition site, the receptor channel
      and the glycine site of the NMDA receptor. In the absence of NMDA, glycine
      increased on its own and in a concentration-dependent manner the depolarization
      evoked release of both CCK-LI and SRIF-LI. This effect of glycine was strychnine
      insensitive and could be mimicked by D-serine, a stereoselective agonist at the
      NMDA receptor glycine site. Antagonists selective for the glycine site or for the
      NMDA receptor channel prevented the effects of glycine/D-serine; these effects
      were, however, insensitive to blockade of the glutamate recognition site of the
      NMDA receptor, suggesting that glutamate released from synaptosomes or present as
      contaminant was not involved. The neuropeptide release elicited by D-serine was
      strongly inhibited by ifenprodil (0.3 microM) and by Zn2+ ions (50 nM), selective
      ligands at the NR2B and NR2A subunits of NMDA receptors, respectively. It is
      concluded that nerve terminals of CCK- and SRIF-releasing neurons possess non
      conventional NMDA receptors whose channels can be operated by glycine or D-serine
      without apparent activation of the glutamatergic coagonist site. These receptors
      may display the triple subunit combination NR1/NR2A/NR2B.

PMID- 9758165
TI  - A novel form of long-term depression in the CA1 area of the adult rat hippocampus
      independent of glutamate receptors activation.
AB  - In young rats, low frequency (1-2 Hz) stimulation of the Schaffer collaterals for
      15 min induces in the CA1 area of the hippocampus a homosynaptic and N-methyl-D
      aspartate receptor-dependent form of long-term depression (LTD) of synaptic
      efficacy. In the adults, while a similar stimulation paradigm is able to depress
      previously potentiated synapses, it leads to conflicting results when applied to
      naive synapses. In the present experiments, different stimulation paradigms have
      been used to induce LTD in the CA1 area of the adult rat hippocampus in vitro.
      Thus, stimulation of the afferent pathway at frequencies higher than those used
      to produce LTD in young animals (5-10 Hz, for 15 min) reliably induced a
      homosynaptic form of LTD. This form of LTD was associated with a significant
      increase in paired-pulse facilitation ratio and was insensitive to ionotropic
      (CNQX, 10 microM and CPP, 20 microM) and metabotropic (S-MCPG, 1 mM) glutamate
      receptors antagonists, suggesting a presynaptic mechanism for both LTD induction
      and expression. In conclusion, our experiments clearly show that LTD is not a
      purely developmental phenomenon but is present also in mature rats, which possess
      the whole machinery for LTD induction and this will greatly enhance the
      flexibility and the storing capacity of neuronal circuits.

PMID- 9758166
TI  - Odour coding is bilaterally symmetrical in the antennal lobes of honeybees (Apis
      mellifera).
AB  - The primary olfactory neuropil, the antennal lobe (AL) in insects, is organized
      in glomeruli. Glomerular activity patterns are believed to represent the across
      fibre pattern of the olfactory code. These patterns depend on an organized
      innervation from the afferent receptor cells, and interconnections of local
      interneurons. It is unclear how the complex organization of the AL is achieved
      ontogenetically. In this study, we measured the functional activity patterns
      elicited by stimulation with odours in the right and the left AL of the same
      honeybee (Apis mellifera) using optical imaging of the calcium-sensitive dye
      calcium green. We show here that these patterns are bilaterally symmetrical (n=25
      bees). This symmetry holds true for all odours tested, irrespective of their role
      as pheromones or as environmental odours, or whether they were pure substances or
      complex blends (n=13 odours). Therefore, we exclude that activity dependent
      mechanisms local to one AL determine the functional glomerular activity. This
      identity is genetically predetermined. Alternatively, if activity dependent
      processes are involved, bilateral connections would have to shape symmetry, or,
      temporal constraints could lead to identical patterns on both sides due to their
      common history of odour exposure.

PMID- 9758167
TI  - Synergistic stimulation of MHC class I and IRF-1 gene expression by IFN-gamma and
      TNF-alpha in oligodendrocytes.
AB  - In order to understand the molecular basis of the synergistic action of
      interferon gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha) on rat
      oligodendrocyte development, we studied some aspects of the signalling pathways
      involved in the regulation of the major histocompatibility complex (MHC) class I
      and the interferon regulatory factor 1 (IRF-1) gene expression. Two well-defined
      inducible enhancers of the MHC class I gene promoter, the MHC class I regulatory
      element (MHC-CRE) and the interferon consensus sequence (ICS), were analysed.
      Neither IFN-gamma nor TNF-alpha was capable of inducing MHC-CRE binding activity
      when administrated alone. Following the exposure of oligodendrocytes to IFN
      gamma, TNF-R1 expression was transcriptionally induced by the binding of signal
      transducer and activator of transcription (STAT-1) homodimers to the IFN-gamma
      activated site (GAS) present in the gene promoter. The upregulation of TNF-R1
      allowed TNF-alpha to induce the binding of nuclear factor-kappaB (NF-kappaB) to
      the MHC-CRE site. With respect to ICS element, IFN-gamma induced IRF-1 binding,
      that was further enhanced upon co-treatment with TNF-alpha. The existence of a
      synergism between IFN-gamma and TNF-alpha in stimulating IRF-1 expression at the
      transcriptional level was supported by IRF-1 promoter analysis: IFN-gamma
      directly induced the binding of STAT-1 homodimers to the GAS element, while NF
      kappaB binding to the kappaB sequence was activated by TNF-alpha only after IFN
      gamma treatment. This transcriptional regulation of IRF-1 gene by IFN-gamma and
      TNF-alpha was confirmed at the mRNA level. The synergism demonstrated in the
      present study highlights the importance of cytokine interactions in magnifying
      their biological effects during brain injury and inflammation.

PMID- 9758168
TI  - Both ET(A) and ET(B) receptors are involved in mitogen-activated protein kinase
      activation and DNA synthesis of astrocytes: study using ET(B) receptor-deficient
      rats (aganglionosis rats).
AB  - Endothelin (ET) is known to be a potent mitogen in astrocytes. However, the
      contribution and signalling pathway of ET(A) and/or ET(B) receptor to the
      proliferation of astrocytes remain unclear. We investigated ET-induced DNA
      synthesis in astrocytes using ET(B) receptor-deficient mutant rats (aganglionosis
      rats: sl/sl). Western blotting with anti-ET receptor subtype-specific antibodies
      and Scatchard analysis of binding revealed that ET(B) receptor expression in
      astrocytes depended on gene dosage (+/+: sl/+: sl/sl=2: 1:0), whereas ET(A)
      receptor expression was unchanged among the three genotypes. ET-1 (10 nM)
      stimulated [3H]thymidine incorporation and mitogen-activated protein kinase (MAP
      kinase) activity not only in +/+ via both ET(A) and ET(B) receptors, but also in
      sl/sl astrocytes via ET(A) receptor with about half the extent of those observed
      in +/+ astrocytes. Treatment with pertussis toxin (PTX) suppressed the ET-1
      induced increases in the incorporation and MAP kinase activity in +/+, but not
      sl/sl astrocytes, indicating that the ET(B) receptor-, but not the ET(A) receptor
      , mediated pathway to DNA synthesis involves PTX-sensitive G proteins, e.g. Gi
      and/or Go (Gi/o). In +/+ astrocytes, ET-1 (1 nM) stimulated cAMP accumulation,
      and the ET(B) receptor-selective agonist IRL 1620 (1 nM) suppressed 10 microM
      forskolin-induced cAMP accumulation, suggesting Gs coupling to the ET(A) receptor
      and Gi/o coupling to the ET(B) receptor. On the other hand, ET-1 did not increase
      cAMP accumulation in sl/sl astrocytes, although ET-1 (1 nM) suppressed the
      forskolin-induced response, suggesting Gi/o coupling to the ET(A) receptor. Our
      results suggest the possibility that the selectivity of G protein for ET(A)
      receptor is changed from Gs to Gi/o in ET(B) receptor-deficient astrocytes.

PMID- 9758169
TI  - Complex regulation of the expression of the polysialylated form of the neuronal
      cell adhesion molecule by glucocorticoids in the rat hippocampus.
AB  - The gyrus dentatus is one of the few areas of the brain that continues to produce
      neurons after birth. The newborn cells differentiate into granule cells which
      project axons to their postsynaptic targets. This step is accompanied by the
      transient expression of the polysialylated isoforms of neuronal cell adhesion
      molecules (PSA-NCAM) by the developing neurons. Glucocorticoid hormones have been
      shown to inhibit neurogenesis. We noted a functional correlation between PSA-NCAM
      expression and glucocorticoid action after manipulation of corticosterone levels
      in the adrenalectomized rat. Adrenalectomy increased neurogenesis, evaluated from
      the incorporation of 5-bromo-2'-deoxyuridine in neuronal precursors, as well as
      PSA-NCAM expression. The increase in PSA-NCAM-immunoreactive (IR) cells in the
      gyrus dentatus, evidenced 72 h following adrenalectomy, persisted for at least a
      month. It was accompanied by enhanced dendritic arborization of PSA-NCAM-IR cells
      in the gyrus dentatus and by an increase in number of PSA-NCAM-IR fibres in the
      CA3 subfield. Neurogenesis was normalized by restitution of diurnal or nocturnal
      levels of corticosterone, whereas normalization of PSA-NCAM expression was only
      observed after simulation of the complete circadian fluctuation of the hormone.
      Our findings reveal the complex action of corticosterone in modulating the
      expression of PSA-NCAM in the gyrus dentatus of the hippocampal formation. They
      also highlight the importance of corticosterone fluctuations in the control of
      neurogenesis and plasticity in this structure.

PMID- 9758170
TI  - Neurotrophin-3 promotes cerebellar granule cell exit from the EGL.
AB  - In the cerebellum, the mRNAs for neurotrophin-3 (NT-3) and its high-affinity
      tyrosine kinase receptor trkC are expressed by both the differentiated granule
      cells of the internal granule cell layer (IGL) and their precursors in the
      external germinal layer (EGL). We have investigated the effects of chronic
      application of exogenous NT-3 in vivo on cerebellar granule cell genesis and
      differentiation. NT-3 was applied to the posterior surface of the rat cerebellum
      from P6 onwards using Elvax implants. At P10 the EGL of cerebellar lobules VII
      and VIII was significantly reduced in thickness in NT-3 implanted rats when
      compared with controls. Immunocytochemical analysis of the EGL using antibodies
      to proliferating cell nuclear antigen (PCNA) revealed that the number of
      postmitotic, premigratory (PCNA-immunonegative) granule cell precursors was
      preferentially reduced in the NT-3 implanted rats. In situ DNA fragmentation
      labelling confirmed that this was not accompanied by increased cell death in the
      EGL. These results suggest that NT-3 promotes the differentiation of postmitotic,
      premigratory granule cell precursors, accelerating cell exit from the EGL.

PMID- 9758171
TI  - Cells in laminae III and IV of the rat spinal cord which possess the neurokinin-1
      receptor receive monosynaptic input from myelinated primary afferents.
AB  - We have previously demonstrated that neurons which have cell bodies in laminae
      III or IV of the rat spinal cord, dendrites that enter the superficial laminae
      and which possess the neurokinin-1 receptor receive a major synaptic input from
      substance P-containing primary afferent axons. In this study we set out to
      determine whether these cells also receive monosynaptic input from myelinated
      primary afferents by using transganglionic transport of the B subunit of cholera
      toxin to identify the central terminals of myelinated afferents from the sciatic
      nerve. Dual-immunofluorescence and confocal microscopy revealed apparent contacts
      between labelled primary afferent terminals and all of the neurokinin-1 receptor
      immunoreactive cells examined, although these contacts were much less numerous
      than those which the cells receive from substance P-containing primary afferents.
      By using a combined confocal and electron microscopic technique we were able to
      confirm that synapses were present at some of the contacts between primary
      afferents and neurokinin-1 receptor-immunoreactive neurons. These results suggest
      that cells of this type will have wide-dynamic range receptive fields, but with a
      relatively strong input from nociceptors.

PMID- 9758172
TI  - Blockade of M2-like muscarinic receptors enhances long-term potentiation at
      corticostriatal synapses.
AB  - Acetylcholine (ACh) exerts a crucial role in learning and memory. The striatum
      contains the highest concentration of this transmitter in the brain. This
      structure expresses two different forms of synaptic plasticity, long-term
      depression (LTD) and long-term potentiation (LTP), which might contribute to the
      storage of motor skills and some cognitive processes. We have investigated the
      role of M2-like muscarinic receptors in striatal LTP by utilizing intracellular
      recordings in vitro from a rat corticostriatal slice preparation. Methoctramine
      (250 nM), an antagonist of M2-like muscarinic receptors, enhanced striatal LTP
      induced in the absence of external magnesium (Mg2+) by high-frequency stimulation
      (HFS) of corticostriatal fibres. Methoctramine did not affect the amplitude of
      excitatory postsynaptic potentials (EPSPs) when bath applied either before or
      after the conditioning tetanus suggesting that a critical increase of ACh
      concentrations is produced only during HFS. Methoctramine per se failed to
      enhance the NMDA-mediated EPSPs recorded in the absence of external Mg2+ and in
      the presence of 10 microM CNQX. Methoctramine antagonized the presynaptic
      inhibitory action of neostigmine, an inhibitor of ACh-esterase, and oxotremorine,
      an agonist of M2-like muscarinic receptors. These data indicate that the
      activation of M2-like muscarinic receptors exerts a negative influence on
      striatal LTP, probably by reducing the release of glutamate from corticostriatal
      fibres and they suggest a complex modulatory effect of ACh in striatal synaptic
      plasticity.

PMID- 9758174
TI  - Calretinin expression as a critical component in the control of dentate gyrus
      long-term potentiation induction in mice.
AB  - We have recently reported that mice homozygous (Cr-/-) for a null mutation in the
      calretinin gene have impaired long-term potentiation (LTP) induction in the
      dentate gyrus (S. Schurmans et al. (1997) Proc. Natl. Acad. Sci. USA, 94, 10415
      ). Here, we investigated dentate LTP induction in mice heterozygous (Cr+/-) for
      the same mutation. Despite the presence of calretinin in neurons of these mice,
      although at reduced levels as compared with normal mice, LTP induction in dentate
      gyrus was totally impaired. Spatial memory and learning were found unaffected in
      Cr+/- mice, such as in Cr-/- mice. Altogether, our results suggest that
      calretinin is a critical component in the control of dentate synaptic plasticity
      in mice, and that levels of calretinin higher than those observed in Cr+/- mice
      are required to induce LTP in this area. The possible mechanisms leading to the
      absence of correlation between gene dosage and biological effects are discussed.

PMID- 9758173
TI  - Expression of the GABA(A) receptor gamma 4-subunit gene: anatomical distribution
      of the corresponding mRNA in the domestic chick forebrain and the effect of
      imprinting training.
AB  - The learning process of imprinting involves morphological, electrophysiological
      and biochemical changes in a region of the chick (Gallus gallus domesticus)
      forebrain known as the intermediate and medial part of the hyperstriatum ventrale
      (IMHV). The alterations include increases in the mean length of postsynaptic
      density profiles of axospinous synapses and the number of N-methyl-D-aspartate
      (NMDA) receptor binding sites, and changes in spontaneous and evoked electrical
      activity. Recent immunocytochemical and behavioural studies have suggested that
      inhibitory GABAergic neurotransmission plays a role in learning. In this context,
      it has previously been reported that a novel avian gamma-aminobutyric acid (GABA)
      type A (GABA(A)) receptor gene, encoding the gamma4 subunit, is highly expressed
      in the hyperstriatum ventrale. In this study, we have used in situ hybridization
      to map, in detail, the expression of the gamma4-subunit gene in the chick brain,
      and to assess the effect of imprinting training on the level of the corresponding
      transcript. Our results reveal that the gamma4-subunit mRNA has a restricted
      distribution, and demonstrate a highly significant, time-dependent effect of
      training on its steady-state level. At 10 h but not at 5 h after training there
      is a decrease (25-32%) in the amount of this transcript in parts of the medial
      hyperstriatum ventrale, including the IMHV. A decrease (28-39%) is also seen in
      certain visual and auditory pathway areas but no effect was observed in other
      forebrain regions such as the hyperstriatum intercalatus superior (HIS). These
      results suggest that imprinting training leads to a time-dependent down
      regulation of GABAergic transmission, and raise the possibility that this down
      regulation plays a role in learning.

PMID- 9758175
TI  - Pediatric tonsillectomy with bipolar electrosurgical scissors.
AB  - PURPOSE: The optimal technique for pediatric tonsillectomy remains a hotly
      debated topic. The speed and superior hemostatic properties of electrosurgical
      dissection must be weighed against the greater tissue preservation and more rapid
      healing of cold dissection techniques. MATERIALS AND METHODS: We have used a new
      surgical device, bipolar electrosurgical scissors, in 30 consecutive pediatric
      tonsillectomies. This instrument provides mechanical cutting with or without
      simultaneous bipolar electrocoagulation. RESULTS: The average surgical time was 6
      minutes. There was no intraoperative blood loss. There were no immediate or late
      post-tonsillectomy hemorrhages. All tonsillar fossae were completely healed at 2
      week follow-up. CONCLUSION: Bipolar electrosurgical scissors provide the best
      properties of both cold dissection and electrosurgical tonsillectomy without
      increasing surgical time or cost.

PMID- 9758176
TI  - Hyoid bone syndrome and its treatment with nonsteroidal anti-inflammatory drugs.
AB  - PURPOSE: Nonspecific cervical pain is a common complaint in primary ear, nose,
      and throat clinic patients. In some cases, hyoid bone syndrome has been
      recognized as the cause of the complaint. Our study describes this common but
      unrecognized syndrome and suggests a treatment with nonsteroidal anti
      inflammatory drugs (NSAIDs), a method of treatment not previously reported for
      this syndrome. PATIENTS AND METHODS: Patients with suspected hyoid bone syndrome
      (38) were treated with oral NSAIDs and/or with an NSAID ointment for topical
      application. RESULTS: Symptomatic relief was obtained in 66% of our patients and
      in 71% of the patients treated by NSAID tablets. Symptomatic relief was obtained
      in 91% of the patients with symptom durations of less than 6 weeks. CONCLUSION:
      We recommend a course of NSAID therapy as the first method of treatment for this
      syndrome before treatment with invasive procedures, especially for patients with
      symptom durations of less than 6 weeks. Better recognition of the hyoid bone
      syndrome will result in a more effective treatment and will avoid an unnecessary
      investigation.

PMID- 9758177
TI  - Bacteria in the middle ear and nasopharynx during tympanostomy tube insertion.
AB  - PURPOSE: To evaluate the efficacy of nasopharyngeal cultures in identifying
      pathogens in middle-ear effusions as an alternative to cultures obtained through
      tympanocentesis. MATERIALS AND METHODS: The study population consisted of 203
      children with middle-ear effusions at the time of placement of tympanostomy tubes
      for recurrent otitis media or persistent otitis media with effusion. Isolates
      from the nasopharynx were compared with those from the middle ear to determine
      sensitivity, specificity, and predictive values for each of the three main
      pathogens. RESULTS: The predominant bacterial isolates from both ear and
      nasopharynx were Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus
      influenzae. Eighty-one percent (42% highly, 39% relatively) S pneumoniae
      nasopharyngeal isolates were resistant to penicillin. The negative predictive
      value of the nasopharyngeal cultures was at least 97% for each of these
      predominant bacteria. CONCLUSION: This study supports the conclusion that
      tympanocentesis is the most useful means of identifying pathogens in otitis
      media.

PMID- 9758178
TI  - Comparison between cartilage and soft tissue ear piercing complications.
AB  - PURPOSE: Despite growing interest in cosmetic piercing, a detailed evaluation of
      associated medical complications is lacking. MATERIALS AND METHODS: A
      questionnaire addressing ear, nose, and other body parts piercing was anonymously
      presented to 1,000 nurses at a major Midwestern teaching hospital, and responses
      were obtained from 552. RESULTS: One hundred sixty (35%) of the 452 nurses who
      had an ear pierced reported a complication. Three hundred fifty-five (30%) of the
      1,200 total pierced sites developed complications that included minor infection
      (77%), allergic reaction (43%), keloid (2.5%), and traumatic tear (2.5%). The
      complication rate from piercing through cartilage (32%) was not significantly
      different from that found when piercing through soft tissue (29%). The type of
      complications experienced differed in frequency between cartilage and soft
      tissue, with minor infection being more prevalent in cartilage piercing (30% v
      21%; P < .10) and allergic reaction found more frequently in soft tissue
      piercings (13% v 4%; P < .025). CONCLUSION: This study identifies a low
      prevalence of major complications (<1%) and a relatively high prevalence of minor
      complications (30%) associated with ear piercing. The expected increase in
      complications and morbidity of piercing through cartilage was not found in this
      study.

PMID- 9758179
TI  - Elderly man presenting with asymptomatic hypercalcemia.

PMID- 9758180
TI  - Eagle's syndrome: a review.

PMID- 9758181
TI  - Polymorphous low-grade adenocarcinoma of the parotid gland.

PMID- 9758182
TI  - Testicular carcinoma metastatic to the neck.
AB  - PURPOSE: To show that a supraclavicular neck mass may be indicative of metastatic
      testicular carcinoma and to offer further insight into the treatment of residual
      neck disease. METHOD: We report six cases of testicular carcinoma metastatic to
      the neck. All were initially treated with radiation, chemotherapy, or a
      combination of both depending on histological type. RESULTS: Neck masses
      persisted despite primary therapy. Three patients underwent subsequent modified
      neck dissection and remained free of disease; three others received nonsurgical
      forms of adjuvant therapy and ultimately died of their cancer. CONCLUSION:
      Metastatic testicular carcinoma may manifest as a supraclavicular neck mass and
      must therefore be considered in the differential diagnosis of a mass in this
      region. Surgical resection is indicated in the management of neck masses that
      persist after cytoreductive chemotherapy to remove residual foci of disease and
      potential source of spread.

PMID- 9758184
TI  - Nasopharyngeal carcinoma in two young brothers and its relationship with Epstein
      Barr virus.

PMID- 9758183
TI  - Merkel cell carcinoma of the external auditory canal invading the intracranial
      compartment.
AB  - PURPOSE: To report an unusual case of an intracranial extension of Merkel cell
      carcinoma originating in the external ear canal and causing neurological
      deficits. CASE REPORT: An 86-year-old woman, with a 16-month history of an
      external auditory canal mass, presented with hemiparesis, facial paralysis, and
      obtundation. Radiographic images showed an intracranial mass extending into the
      petrous bone. METHOD: The patient had a craniotomy for intracranial tumor
      resection with concurrent mastoidectomy for facial nerve decompression and
      obtundation and hemiparesis were resolved. Residual tumor was subsequently
      treated with adjuvant radiation therapy, and facial nerve function consequently
      improved. CONCLUSION: Merkel cell tumors rarely invade the intracranial
      compartments. Residual tumor and neurological deficits may respond to adjuvant
      radiation therapy.

PMID- 9758185
TI  - Symptomatic presentation of an enlarged, ossified triticeal cartilage.

PMID- 9758186
TI  - Ectopic thyroid gland simulating a submandibular tumor.

PMID- 9758188
TI  - Development of interpersonal communication.

PMID- 9758187
TI  - Traumatic myositis ossificans of the levator scapulae muscle.

PMID- 9758189
TI  - Class size and the quality of educational outcomes.

PMID- 9758190
TI  - Routes from research to clinical practice in child psychiatry: retrospect and
      prospect.
AB  - The last 40 years has seen a virtual revolution in both medical research and
      medical practice. Child psychiatry has been part of that revolution. The
      situation in the 1950s is briefly noted and seven examples are used to illustrate
      how causal research in the past has led to changes in clinical practice. The
      areas used as examples comprise: autism, hyperactivity/attention deficit
      syndromes, conduct disorders, depressive conditions, genetic research, organic
      brain dysfunction, and psychosocial risk processes. Prospects for the future with
      respect to the impact of research on clinical practice are discussed in relation
      to molecular genetics, environmental risks, cognitive and affective processing of
      experiences, links across the lifespan, and functional brain imaging. Attention
      is drawn to implications for training as well as for practice.

PMID- 9758191
TI  - The Emanuel Miller Memorial Lecture 1997. Change and continuity in the
      development of children with autism.
AB  - The developmental approach to childhood psychopathology identifies deviations
      from typical patterns of development and stability of individual characteristics
      over time, and precursors in early life of later functions. The application of
      this approach to the social, communicative, and cognitive development of children
      with autism is discussed. Results from a longitudinal study of children with
      autism and other developmental disorders are described, indicating that children
      with autism have stable deficits in joint attention, representational play, and
      responsiveness to the emotions of others, and that early variations in these
      abilities are important for concurrent and subsequent language development and
      for peer engagement many years later.

PMID- 9758192
TI  - Information processing deficits associated with developmental coordination
      disorder: a meta-analysis of research findings.
AB  - A meta-analysis was conducted to identify information processing factors that
      characterise children with Developmental Coordination Disorder (DCD). A total of
      50 studies yielded 374 effect sizes based on 983 DCD and 987 control children. A
      mild generalised performance deficit was indicated, since motor-impaired children
      were inferior on almost all measures of information processing. There were,
      however, several areas where their deficiencies were more pronounced. The
      greatest deficiency was in visual-spatial processing. This was evident regardless
      of whether or not the tasks involved a motor component. Most other deficiencies
      were in the small-to-moderate range and included kinaesthetic and cross-modal
      processing. The findings support the notion that perceptual problems,
      particularly in the visual modality, are associated with difficulties in motor
      coordination.

PMID- 9758193
TI  - Inattention, impulsivity, and hyperactivity from preschool to school age:
      performance of hard-to-manage boys on laboratory measures.
AB  - Boys identified as hard-to-manage at age 4 and age-matched controls were assessed
      on laboratory measures of inattention, impulsivity, and hyperactivity at ages 4,
      6, and 9. Hard-to-manage boys still exhibited some behavioral difficulties at age
      9, but were not more inattentive or impulsive than controls. Boys with Attention
      Deficit Disorder (ADD) at age 9 showed performance deficits in each symptom
      related domain relative to problem boys without ADD and controls. However, hard
      to-manage problem boys with and without ADD did not differ on most earlier
      measures of inattention, impulsivity, and hyperactivity, suggesting that symptoms
      specific to ADD emerged more clearly between ages 6 and 9.

PMID- 9758194
TI  - Language, social cognitive processing, and behavioral characteristics of
      psychiatrically disturbed children with previously identified and unsuspected
      language impairments.
AB  - This study examined characteristics of social cognitive processing, psychiatric
      disorder, and behavioral ratings of 380 children aged 7 to 14 years who had been
      referred consecutively for child psychiatric services with identified and
      unsuspected language impairments and with normally developing language. The
      results indicated that children with language impairments generally exhibited
      greater deficits in social cognitive processing, and particularly emotion
      decoding and social problem solving, than children who have language that is
      developing normally. Differences in psychiatric diagnosis and behavior problems
      were observed only between children with previously identified language
      impairments and children with normally developing language; children with
      previously identified language impairments were more likely to be diagnosed as
      having Attention Deficit Hyperactivity Disorder (ADHD) and to be rated by both
      parents and teachers as having more severe attentional problems. In addition,
      teachers rated them as more socially withdrawn. The results suggest that it is
      important to incorporate measures of both social cognition and language
      functioning routinely into clinical assessment, something that currently is
      rarely done.

PMID- 9758195
TI  - Language, achievement, and cognitive processing in psychiatrically disturbed
      children with previously identified and unsuspected language impairments.
AB  - This study examined the language, achievement, and cognitive characteristics of
      380 children, aged 7 to 14 years, consecutively referred to child psychiatric
      services. Among those children referred solely for psychiatric problems, 40% had
      a language impairment that had never been suspected. Children with previously
      identified and unsuspected language impairments were similar with respect to
      receptive and expressive language and on measures of cognitive processing.
      Although both groups of children with language impairments exhibited poorer
      academic achievement than children with normal language, children with previously
      identified language impairments had the lowest achievement. The milder
      achievement problems of children with unsuspected language impairment may explain
      why their problems had not been suspected. Both the clinical and theoretical
      implications of the findings are discussed. Heightened awareness concerning the
      high frequency of language impairment and other cognitive processing problems in
      children referred for psychiatric assessment and treatment should lead to more
      systematic examination of language functioning and evaluation of the impact of
      language and communication functioning on therapeutic outcomes.

PMID- 9758196
TI  - Development of the Children's Communication Checklist (CCC): a method for
      assessing qualitative aspects of communicative impairment in children.
AB  - The Children's Communication Checklist (CCC) was developed to assess aspects of
      communicative impairment that are not adequately evaluated by contemporary
      standardised language tests. These are predominantly pragmatic abnormalities seen
      in social communication, although other qualitative aspects of speech and
      language were also included. Some items covering social relationships and
      restricted interests were incorporated, so that the relationship between
      pragmatic difficulties and other characteristics of pervasive developmental
      disorders could be explored. Checklist ratings were obtained for 76 children aged
      7 to 9 years, all of whom had received special education for language impairment.
      In 71 cases, 2 raters (usually a teacher and speech-language therapist)
      independently completed the checklist, making it possible to establish inter
      rater reliability. From an initial pool of 93 items, 70 items, grouped into 9
      scales, were retained. Five of the subscales were concerned with pragmatic
      aspects of communication. A composite pragmatic impairment scale formed from
      these subscales had inter-rater reliability and internal consistency of around
      .80. This composite discriminated between children with a school diagnosis of
      semantic-pragmatic disorder and those with other types of specific language
      impairment (SLI). The majority of children with pragmatic language impairments
      did not have any evidence of restricted interests or significant difficulties in
      the domains of social relationships.

PMID- 9758197
TI  - Are there subgroups within the autistic spectrum? A cluster analysis of a group
      of children with autistic spectrum disorders.
AB  - Comprehensive data on the developmental history and current behaviours of a large
      sample of high-functioning individuals with diagnoses of autism, Asperger's
      syndrome, or other related disorder were collected via parent interviews. This
      provided the basis for a taxonomic analysis to search for subgroups. Most
      participants also completed theory of mind tasks. Three clusters or subgroups
      were obtained; these differed on theory of mind performance and on verbal
      abilities. Although subgroups were identified which bore some relationship to
      clinical differentiation of autistic, Asperger syndrome, and Pervasive
      Developmental Disorder Not Otherwise Specified (PDD-NOS) cases, the nature of the
      differences between them appeared strongly related to ability variables.
      Examination of the kinds of behaviours that differentiated the groups suggested
      that a spectrum of autistic disorders on which children differ primarily in term
      of degrees of social and cognitive impairments could explain the findings.

PMID- 9758199
TI  - Diagnostic rules for children with PDD-NOS and multiple complex developmental
      disorder.
AB  - This study was designed to examine the classification performance of diagnostic
      rules for pervasive developmental disorder not otherwise specified (PDD-NOS) and
      multiple complex developmental disorder (McDD), with clinical diagnosis as the
      gold standard. McDD is an heuristic concept of a developmental disorder
      characterised by social impairments, affective dysregulation, and thought
      disturbance. Detailed information on the symptoms, reliably extracted from the
      charts of 103 children with PDD-NOS and McDD, 32 with autistic disorder, and 96
      with non-PDD disorders, was used to determine the presence of the DSM-IV criteria
      of autistic disorder and the criteria of McDD. A scoring rule for PDD-NOS based
      on a short set of seven DSM-IV criteria with a cut-off point of three items and
      one social interaction item set as mandatory had the best balance between high
      sensitivity and high specificity. The most effective and simple rule based on
      McDD criteria had a cut-off of three items, out of six items of anxieties and
      thought disturbance.

PMID- 9758198
TI  - The development of theory of mind in deaf children.
AB  - Deaf children aged 4 to 16 years were given a false-belief test of theory of
      mind. Although the children experienced difficulty with the test, relative to
      hearing children, confirming a report by Peterson and Siegal (1995), performance
      was age-related, with a significantly higher proportion of 13- to 16-year-olds
      passing the test. It was concluded that deaf children raised in a spoken language
      environment show a developmental delay in theory of mind acquisition. This delay
      is consistent with the assumption that their early opportunities for learning
      about mental states are relatively restricted and that the normal development of
      theory of mind is dependent upon such opportunities.

PMID- 9758200
TI  - Sociometric classification methods in school peer groups: a comparative
      investigation.
AB  - The categorical consequences and psychometric properties of different sociometric
      classification methods were evaluated. Children aged 9 to 12 years (N = 254)
      completed three sociometric questionnaires and a peer assessment measure on two
      occasions 5 weeks apart. The sociometric data were analysed using 13 different
      methods. Analysis of kappa values indicated relatively poor agreement across
      methods on subject classification. Temporal stability of the classifications was
      also poor. Assessment of construct validity involved analysis of the peer
      assessment items, using MANOVA to test hypotheses based on ideas from social
      exchange theory. Cross-sex rating biases and difficulties with the neglected and
      controversial classifications are discussed as indicating a need for the
      application of theoretically based approaches which consider features of the peer
      group social system and a need for caution in selecting methods for clinical use.

PMID- 9758201
TI  - The relationship between endothelins and eicosanoids in the vasculature.

PMID- 9758202
TI  - Dietary borage oil alters plasma, hepatic and vascular tissue fatty acid
      composition in spontaneously hypertensive rats.
AB  - Dietary borage oil rich in gamma-linolenic acid (GLA) has been shown to lower
      blood pressure in Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). A
      potential mechanism for this effect may be attributed to changes in metabolism of
      GLA to dihomogamma-linolenic (DGLA) and arachidonic acids (AA). We investigated
      the effects of dietary borage oil on fatty acid composition in the plasma, liver
      and vascular tissue in WKY and SHR. The diet significantly increased the levels
      of omega-6 polyunsaturated fatty acids. GLA and DGLA levels in the plasma, liver,
      aorta and renal artery tissues increased in SHR (P < 0.001) and WKY (P < 0.001).
      AA levels were also increased in both plasma and liver of SHR (P < 0.05) and WKY
      (P < 0.05) fed the borage oil enriched diet. The results demonstrate that dietary
      borage oil produces marked changes in the metabolism of GLA which may contribute
      to its blood pressure lowering effect in WKY and SHR.

PMID- 9758203
TI  - Effective long-term inhibition of thromboxane production but not of serotonin
      release in patients with coronary heart disease by 30 mg/d acetylsalicylic acid
      dosage.
AB  - Efficacy of aspirin (Acetylsalicylic acid, ASA) antiaggregatory prevention was
      demonstrated in a series of clinical trials. The recommended ASA doses decreased
      gradually and doses 50-30 mg ASA/d are intensively studied at the present time. A
      group of 42 patients with coronary heart disease was evaluated: (1) Basal TXB2
      production during spontaneous blood clotting was 360 +/- 37.6 ng/ml; (2) Two
      initial doses were tested: while 200 mg ASA inhibited, during spontaneous blood
      clotting, median TXB2 production by 99.9% (serum TXB2 concentration 1.35 ng/ml),
      30 mg ASA median inhibition was just 42.0% (serum TXB2 151 ng/ml); (3) 30 mg
      ASA/d maintenance dose was evaluated for 3 months. The median TXB2 production
      inhibition was 98.5% (serum TXB2 3.75 ng/ml, first month) and 94.0% (serum TXB2
      14.2 ng/ml, third month); (4) Four patients did not respond sufficiently, because
      of noncompliance verified by the determination of salicyluric acid urinary
      excretion, the lower limit of excretion being <3 micromol/2 h; (5) Both initial
      and maintenance ASA dose decreased metabolic TXA2 endproducts in urine; (6) 5HT
      platelet release did not decrease; (7) Potential changes of 5HT metabolic
      elimination were excluded by the simultaneous determination of 5
      hydroxyindoleacetic acid (5HIAA). In conclusion, 200 mg initial dose and 30 mg
      ASA/d maintenance dose are suggested to be maximally inhibitory for TXB2
      production without influence on 5HT release.

PMID- 9758205
TI  - Diet can manipulate the metabolism of EPA and GLA in erythrocyte membrane and
      plasma.
AB  - The effect of diet on the metabolism of eicosapentaenoic acid (EPA) and
      gammalinolenic acid (GLA) was investigated in two groups of African Green Vervet
      monkeys fed either a Western atherogenic diet (WAD; %E fat 43.5%; P:S 0.3; n=10)
      or a high carbohydrate diet (HCD; %E fat 20.5%; P:S 3.4; n=10). Vervets within
      each dietary treatment were supplemented with 300 mg/day with either an EPA
      concentrate (50% as free fatty acid, n=5) or a GLA concentrate (70% as free fatty
      acid, n=5) for 24 weeks, increasing the dose every 6 weeks to a maximum of 2400
      mg/kg/day. Vervets in the WAD-Group consumed 433.7 mg/kg/day of EPA and those in
      the HCD-Group 318.2 mg/kg/day of EPA, whereas 421 mg/kg/day of GLA was consumed
      in the WAD Group and 340 mg/kg/day in the HCD Group during the last 6 weeks (week
      18-24) of the supplementation period. The rate of disappearance of EPA and GLA
      from plasma and erythrocyte memebrane (EMB) phospholipids were estimated for the
      two diets after supplementation was stopped. The half-lives (t(1/2)) of EPA in
      EMB phosphatidylcholine (PC) were estimated to be 34.6 days (WAD) and 22.6 days
      (HCD), compared to 43.5 days (WAD) and 31.3 days (HCD) in EMB
      phosphatidylethanolamine (PE). In plasma cholesteryl ester (CE) t(1/2) was 23.5
      days (WAD) compared to 14.1 days (HCD), and in plasma triacylglycerol (TAG) 17.4
      days (WAD) compared to 9.4 days (HCD). Although accurate estimation of the GLA
      t(1/2) was difficult to assess due to the low tissue levels (probably due to
      rapid conversion to DGLA), the disappearance rates of GLA from EMB and plasma
      also suggested a faster metabolic rate in those animals consuming a HCD compared
      to a WAD. EPA also disappeared faster from EMB PC than from EMB PE. Disappearance
      of EPA from plasma TAG was also faster than from plasma CE, probably reflecting
      their relative turnover and metabolic rates. During supplementation, EPA
      substituted linoleic acid (C18:2 n-6), arachidonic acid (C20:4 n-6), and GLA
      (C18:3 n-6). This was reversed when supplementation was stopped. Plasma total
      cholesterol (TC) levels decreased by 17.06 +/- 17.67% in animals consuming the
      HCD with EPA as supplement, whereas in those consuming the WAD, plasma TC levels
      increased with 21.78 +/- 28.23% during the supplementation period. The delay of
      EPA and GLA disappearance from EMB and plasma in animals consuming a WAD,
      strongly suggests that metabolism of EPA and GLA is modulated by diet. Such a
      modulation could cause an accumulation of plasma TC levels that could explain the
      contradictory results reported by previous studies.

PMID- 9758204
TI  - Effects of inhibitors of nitric oxide synthase on isolated uteri of fasting rats.
AB  - The effects of inhibitors of nitric oxide synthase on the glucose metabolism of
      uteri isolated from 4-day underfed rats were studied. In control rats receiving
      normal feeding, the addition of indomethacin (5 x 10(-6) M); acetyl salicylic
      acid (10(-4) M); 400 microM of N(G)methyl-L-arginine, (L-NMMA) or 400 microM of
      sodium nitroprusside (SNP), does not modify the production of 14CO2 from U14C
      glucose. On the contrary, in fasted rat uteri, indomethacin increases glucose
      oxidation significantly, while acetyl salicylic acid does not alter it. Also, the
      addition of L-NMMA has no effect. In another group of experiments, in the
      preparations containing indomethacin of uteri isolated from underfed rats, the
      addition of L-NMMA significantly changes the effect of indomethacin. Another
      inhibitor of nitric oxide synthase, N(omega)nitro-L-arginine methyl ester (L
      NAME), or hemoglobin (2 microg ml(-1)) a nitric oxide scavenger have the same
      effects while N(omega)nitro arginine-D-methyl ester (D-NAME) does not. However
      (SNP), a nitric oxide donor, does not alter the production of 14CO2 in uteri
      isolated from fasted rats. These results show that in underfed rats, indomethacin
      increases glucose oxidation independently from its inhibiting effect on
      cyclooxygenase. Specific inhibitors of nitric oxide synthase can reverse this
      effect.

PMID- 9758206
TI  - Incorporation of delta 5 desaturase substrate (dihomogammalinolenic acid, 20:3 n
      6) and product (arachidonic acid 20:4 n-6) into rat liver cell nuclei.
AB  - The incorporation of [1-(14)C]20:3 n-6 and its desaturation product, [1
      (14)C]20:4 n-6 into nuclear lipids from rat liver cells were investigated during
      in vitro delta5 desaturation. [1-(14)C]20:3 n-6 activated as 20:3 n-6-CoA by
      nuclear long chain acyl-CoA synthetase was: (1) incorporated into nuclear lipids
      mainly esterified to phospholipids and in a lesser proportion, to triglycerides
      and diglycerides; and (2) desaturated to 20:4 n-6-CoA by the nuclear delta5
      desaturase. The amount of [1-(14)C]20:4 n-6 acid synthesized in cell nuclei
      increased along with time and was stimulated by the cytosol fraction. The major
      proportion of 20:4 n-6 was found in phospholipids and in a lesser proportion it
      remained as free fatty acids and was esterified to triglycerides and
      diglycerides. 20:4 n-6-CoA was incorporated into nuclear lipids and hydrolyzed to
      free fatty acid. These results indicate that liver cell nuclei possess the
      necessary enzymes to incorporate the delta5 desaturase substrate (20:3 n-6) as
      well as the product of desaturation (20:4 n-6) into nuclear TG, DG and PL
      following an acyl-CoA dependent pathway.

PMID- 9758207
TI  - Effects of PGE2 and of different synthetic PGE derivatives on the glycosylation
      of pig gastric mucins.
AB  - The glycosylation of pig gastric mucins, discharged in response to prostaglandin
      (PG) E2 and to three synthetic PGE-derivatives (misoprostol, nocloprost,
      rioprostil) was compared. After a 20 h culture period in the absence or presence
      of 1 micromol/l of one of the PGs, mucins were isolated by gel chromatography and
      their glycosylation characterized by their linkage to a panel of lectins. For all
      tested PGs, a significantly increased lectin linkage to mucin glycoproteins of
      high molecular weight was detected; no significant effects were observed for low
      molecular weight glycoproteins. Within the stimulatory pattern, major effects
      were found for the linkage of peanut agglutinin and soybean agglutinin,
      suggesting predominant effects on the expression of galactose and N-acetyl
      galactosamine. Only minor effects were found for sialic acid, mannose, N-acetyl
      glucosamine and fucose expression, as evidenced by the linkage of Sambucus nigra
      agglutinin, Concanavalin A, Datura stramonium agglutinin and Ulex europaeus I
      agglutinin. All PGs exerted a similar stimulatory pattern. However, at the
      indicated concentration, misoprostol (281 +/- 36% of control) rendered a
      significantly higher overall effect than PGE2 (208 +/- 31%), whereas the
      increases induced by nocloprost (237 +/- 35%) and rioprostil (202 +/- 35%) were
      not significantly different from the PGE2 effects. These results, suggesting
      similar stimulatory effects of PGE2 and of the tested synthetic PGs on
      glycosylation of mucin oligosaccharides, discharged from mucous cells during an
      in vitro culture, may, at least in part, explain clinical findings that during an
      impairment of the endogenous PG synthesis, the tested synthetic PGs are effective
      exogenous substitutes for endogenous E-type prostaglandins and act as anti-ulcer
      drugs.

PMID- 9758208
TI  - Systematic pharmacological approach to the characterization of NSAIDs.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the treatment
      of inflammatory diseases. NSAIDs inhibit cyclooxygenase (COX), the rate limiting
      enzyme responsible for the conversion of arachidonic acid into prostaglandins.
      Recent studies have shown the existence of two isoforms of cyclooxygenase: COX-1,
      now often referred to as the constitutive form, and COX-2, an inducible form
      which is the major isoenzyme involved in prostaglandin synthesis in inflammation
      and other pathological situations. Since inhibition of prostaglandin production
      in tissues where they play a physiological role leads to important side effects,
      a COX-2 preferential inhibitor would present therapeutical advantages. In the
      present study, we evaluated the inhibitory properties of cyclooxygenase
      inhibitors on human COX-1 and COX-2 using a heterologous expression system. We
      investigated instantaneous inhibition and pre-incubation inhibition as well as
      time recovery of cyclooxygenase activity assays with the aid of four NSAIDs:
      mefenamic acid, indomethacin, aspirin and NS-398. Our results demonstrate that
      instantaneous inhibition assays have little correlation with clinical results.
      Inhibition assays using pre-incubation with the drugs tested, however, more
      closely resemble the data from in vivo studies. Cyclooxygenase recovery assays
      enabled better characterization of simple competitive inhibitors, competitive
      reversible time-dependent inhibitors and irreversible time-dependent inhibitors.
      The data illustrate the usefulness of our system in allowing a better
      determination of the pharmacological characteristics of NSAIDs as well as
      permitting a comparison among different drugs.

PMID- 9758209
TI  - Interleukin-1 beta and dexamethasone regulate gene expression of prostaglandin H
      synthase-2 via the NF-kB pathway in human amnion derived WISH cells.
AB  - Interleukin-1beta (IL-1beta) stimulated PGE2 synthesis in human amnion derived
      WISH cells, whereas dexamethasone blocked IL-1beta-mediated stimulation of PGE2
      production. Sequence analysis of the 5'-flanking region of the human
      prostaglandin H synthase-2 (PGHS-2) gene indicates two putative NF-kB binding
      sites. Mutation of a single site or both sites resulted in significantly
      decreased activity of the PGHS-2 promoter. IL-1beta treatment increased
      significantly the native promoter activity and this increase was attenuated by
      using the NF-kB-mutant promoter. Dexamethasone treatment also decreased the IL
      1beta mediated stimulation of the PGHS-2 native promoter but not the NF-kB mutant
      promoter. Furthermore, the involvement of the NF-kB was supported by
      electrophoretic mobility shift assay which revealed an increased nuclear binding
      of the NF-kB probe upon IL-1beta induction and a decreased nuclear binding of the
      NF-kB probe upon dexamethasone pre-treatment. These results provide convincing
      evidence that NF-kB may mediate the IL-1beta stimulation of PGHS-2 gene
      expression as well as the dexamethasone inhibition of the IL-1beta induction
      process in WISH cells.

PMID- 9758210
TI  - Eicosanoid profile in cultured human pulmonary artery smooth muscle cells treated
      with IL-1 beta and TNF alpha.
AB  - Interleukin-1beta (IL-1beta) and tumor necrosis factor (TNF alpha) induce
      prostanoid biosynthesis in vascular smooth muscle cells by promoting
      cyclooxygenase (COX) expression, but little is known about the biosynthesis of
      lipoxygenase (LPO) metabolites. We investigated the effects of human recombinant
      IL-1beta and TNF alpha on the production of arachidonic acid (AA) metabolites by
      high-performance liquid chromatography (HPLC). After being labelled with 3H-AA,
      cultured human pulmonary artery smooth muscle cells (HPASMC) were incubated with
      or without IL-1beta (200 U/ml) and TNF alpha (500 U/ml). The arachidonic acid
      metabolites released from HPASMC were then analysed by HPLC. In control HPASMC, 6
      keto-PGF1alpha and PGE2 were the principal metabolites of the COX pathway, while
      5-HETE, LTC4 and D4 were the main products of the LPO pathway. HPASMC treated
      with 200 U/ml of IL-1beta and 500 U/ml of TNF alpha produced more COX metabolites
      such as 6-keto-PGF1alpha, thromboxane B2, PGF2alpha and PGE2 than control cells.
      Significant increases in the production of LPO derivatives such as LTB4, C4, D4,
      and 15-HETE were also found in IL-1beta-treated HPASMC. Although the release of
      LPO products tended to increase in TNF alpha-treated cells, no significant change
      was noted. Many AA metabolites including LTB4 are responsible for the
      inflammatory process in vivo. AA metabolites produced by pulmonary artery smooth
      muscle cells might play important roles in cytokine-mediated acute lung injury
      and inflammation.

PMID- 9758211
TI  - Use of a semi-automated, robotic radioimmunoassay to measure cAMP generated by
      activation of DP-, EP2-, and IP-prostaglandin receptors in human ocular and other
      cell types.
AB  - The aim of these studies was to compare the effects of several prostaglandin
      agonists on adenylyl cyclase activity in embryonic bovine tracheal (EBTr) cells,
      transformed human nonpigmented ciliary epithelial (NPE) cells and National Cancer
      Bank (NCB-20) cells. These cell types have been shown to express DP, EP2 and IP
      prostaglandin (PG) receptors, respectively. Cyclic AMP (cAMP) generation was
      measured by manual and semi-automated radioimmunoassay (RIA) techniques. ZK118182
      (EC50 = 10-27 nM), PGE2 (EC50 = 21-27 nM) and PGI2 (EC50 = 3.5-4 nM) had the
      highest potency at the DP, EP2 and IP receptors, respectively. A plot of potency
      (EC50) values generated with both techniques showed a high degree of correlation
      for all three receptors. These studies provide further characterization of
      prostanoid receptor functional responses in three cell types and demonstrate the
      advantages of a semi-automated RIA method for the analysis of the second
      messenger cAMP.

PMID- 9758212
TI  - Reciprocal up- and down-regulation of BDNF mRNA in tetanus toxin-induced
      epileptic focus and inhibitory surround in cerebral cortex.
AB  - Chronic focal epilepsy is associated with synaptic plasticity and growth of new
      connections. Brain-derived neurotrophic factor (BDNF) is associated with each of
      these processes in normal brain and shows acute up-regulation in models of
      generalized epilepsy. Here, using an experimental model of focal epilepsy, we
      show persistent up-regulation of BDNF mRNA, independent of that of other growth
      factors, in association with the development and persistence of chronic seizures.
      In situ hybridization histochemistry revealed that rats perfused within 2-3 days
      after seizure onset had widespread increases in BDNF mRNA levels in the
      neocortex. Rats perfused at later times, however, showed focal up-regulation of
      BDNF mRNA at the injection site and down-regulation in a surrounding cortical
      zone. Nerve growth factor and neurotrophin-3 mRNAs were not significantly
      altered. These reciprocal changes in BDNF gene expression in the epileptic focus
      and the cortical surround may contribute to plastic changes in epileptic neuronal
      circuits that accompany the transition from acute to chronic epilepsy. BDNF down
      regulation in the surround is likely to be associated with the inhibitory
      surround that hampers seizure spread, but facilitates the persistence of a
      chronic epileptic focus.

PMID- 9758213
TI  - Cortical variability and asymmetry in normal aging and Alzheimer's disease.
AB  - The onset of Alzheimer's disease (AD) is accompanied by a complex and distributed
      pattern of neuroanatomic change, difficult to distinguish clinically from dynamic
      alterations in normal aging. Extreme variations in the sulcal patterns of the
      human cortex have made it difficult to identify diffuse and focal variations in
      cortical structure in neurodegenerative disease. We report the first
      comprehensive 3D statistical analysis of deep sulcal structure in vivo, in both
      normal aging and dementia. High-resolution 3D T1-weighted fast SPGR (spoiled
      GRASS) MRI volumes were acquired from 10 patients diagnosed with AD (NINCDS-ARDRA
      criteria; age: 71.9 +/- 10.7 years) and 10 normal subjects matched for age (72.9
      +/- 5.6 years), gender, educational level and handedness. Scans were digitally
      transformed into Talairach stereotaxic space. To determine specific patterns of
      cortical variation in dementia patients, 3D average and probabilistic maps of
      primary deep sulci were developed for both normal and AD groups. Major sulci
      (including supracallosal, cingulate, marginal, parieto-occipital, anterior and
      posterior calcarine sulci, and Sylvian fissures) were modeled as complex systems
      of 3D surfaces using a multi-resolution parametric mesh approach. Variations and
      asymmetries in their extents, curvature, area and surface complexity were
      evaluated. Three-dimensional maps of anatomic variability, structural asymmetry
      and local atrophy indicated severe regionally selective fiber loss in AD. A
      midsagittal area loss of 24.5% at the corpus callosum's posterior midbody (P <
      0.025) matched increases in structural variability in corresponding temporo
      parietal projection areas. Confidence limits on 3D cortical variation, visualized
      in 3D, exhibited severe increases in AD from 2 to 4 mm at the callosum to a peak
      SD of 19.6 mm at the posterior left Sylvian fissure. Normal Sylvian fissure
      asymmetries (right higher than left; P < 0.0005), mapped for the first time in
      three dimensions, were accentuated in AD (P < 0.0002), and were greater in AD
      than in controls (P < 0.05). Severe AD-related increases in 3D variability and
      asymmetry may reflect disease-related disruption of the commissural system
      connecting bilateral temporal and parietal cortical zones, regions known to be at
      risk of early metabolic dysfunction, perfusion deficits and selective neuronal
      loss in AD.

PMID- 9758214
TI  - View-invariant representations of familiar objects by neurons in the inferior
      temporal visual cortex.
AB  - A view-invariant representation of objects in the brain would have many
      computational advantages. Here we describe a population of single neurons in the
      temporal visual cortex (IT) that have view-invariant representations of familiar
      objects. Ten real plastic objects were placed in the monkeys' home cages for a
      period of time before neurophysiological experiments in which neuronal responses
      were measured to four views of each object. The macaques performed a visual
      fixation task, and had never been trained in object discrimination. The majority
      of the visual neurons recorded were responsive to some views of some objects
      and/or to the control stimuli, as would be expected from previous studies.
      However, a small subset of these neurons were responsive to all views of one or
      more of the objects, providing evidence that these neurons were coding for
      objects, rather than simply for individual views or visual features within the
      image. This result was confirmed by information theoretic analyses, which showed
      that the neurons provided information about which object was being seen,
      independently of the view. The coding scheme was shown to be sparse distributed,
      with relatively independent information being provided by the different neurons.
      Hypotheses about how these view-invariant cells are formed are described.

PMID- 9758215
TI  - Nonlinear dynamics of 3 Hz spike-and-wave discharges recorded during typical
      absence seizures in children.
AB  - One-channel routine recordings of the scalp electroencephalogram (EEG) from
      unmedicated children strictly classified as unprovoked typical (3 c/s) absence
      seizures were selected. The dynamics of spike-and-wave discharges (SWD) were then
      examined by means of autocorrelation, correlation dimension, averaged pointwise
      dimension and largest Lyapunov exponent. For one EEG signal with pronounced spike
      and-wave (SW) patterns, these measures were used complementary to a surrogate
      data method, a nonlinear (SETAR) modeling approach, and a SW simulation procedure
      providing five types of SW test signals. The SETAR model exhibited stationary SW
      dynamics, visually very similar to the EEG target signal, and with clear
      nonlinear structure. According to the results, the EEG episodes investigated
      represent low-dimensional dynamics, possibly recorded during nonstationary
      periods. Arguments that justify the assumption of deterministic chaos in our EEG
      signals were not obtained with the current methods. From the results one may
      conclude that two global oscillatory modes are present for the model, and three
      modes are active during the EEG recording period.

PMID- 9758216
TI  - Cerebral blood flow relationships associated with a difficult tone recognition
      task in trained normal volunteers.
AB  - Tone recognition is partially subserved by neural activity in the right frontal
      and primary auditory cortices. First we determined the brain areas associated
      with tone perception and recognition. This study then examined how regional
      cerebral blood flow (rCBF) in these and other brain regions correlates with the
      behavioral characteristics of a difficult tone recognition task. rCBF changes
      were assessed using H2(15)O positron emission tomography. Subtraction procedures
      were used to localize significant change regions and correlational analyses were
      applied to determine how response times (RT) predicted rCBF patterns. Twelve
      trained normal volunteers were studied in three conditions: REST, sensory motor
      control (SMC) and decision (DEC). The SMC-REST contrast revealed bilateral
      activation of primary auditory cortices, cerebellum and bilateral inferior
      frontal gyri. DEC-SMC produced significant clusters in the right middle and
      inferior frontal gyri, insula and claustrum; the anterior cingulate gyrus and
      supplementary motor area; the left insula/claustrum; and the left cerebellum.
      Correlational analyses, RT versus rCBF from DEC scans, showed a positive
      correlation in right inferior and middle frontal cortex; rCBF in bilateral
      auditory cortices and cerebellum exhibited significant negative correlations with
      RT These changes suggest that neural activity in the right frontal, superior
      temporal and cerebellar regions shifts back and forth in magnitude depending on
      whether tone recognition RT is relatively fast or slow, during a difficult,
      accurate assessment.

PMID- 9758217
TI  - Constant and variable aspects of axonal phenotype in cerebral cortex.
AB  - In order to determine to what extent the terminal arbors of phylogenetically and
      functionally distant axons are constructed according to common rules, we have
      compared visual callosal axons in cats (CCC axons) with thalamocortical axons to
      the whisker representation in mice (MTC axons). Both similarities and differences
      were found. Maximal order of branching, branching angles, topological
      distribution of branches and boutons are similar for all axons, indicating strong
      constraints in arbor formation. CCC and MTC axons are indistinguishable for total
      arbor length and number of branches, although these parameters can vary across
      individual axons of each group. MTC axons have longer and bouton-richer end
      branches (the 'transmission compartment') while, in CCC axons, proximal,
      boutonless branches (the 'conduction compartment') predominate. Therefore, the
      two classes of axons appear to be specialized for performing different types of
      operations, in agreement with the available electrophysiological data and
      computer simulations. Differences in the length of branches were also observed
      between MTC axons of normal and 'barrelless' mice, suggesting that this parameter
      can be regulated by conditions at the terminal sites.

PMID- 9758218
TI  - A neural model of binocular integration and rivalry based on the coordination of
      action-potential timing in primary visual cortex.
AB  - In normal vision, the inputs from the two eyes are integrated into a single
      percept. When dissimilar images are presented to the two eyes, however, they
      compete for perceptual dominance, so that one eye's view suppresses that of the
      other. Recent evidence suggests that this phenomenon, known as binocular rivalry,
      arises through competition between alternative stimulus interpretations in
      extrastriate cortex. Because eye-specific information appears to be lost at this
      stage, it remains unclear how the stimulus conditions that yield binocular
      rivalry are distinguished from those that produce stable single vision. Using a
      neural network that models the mammalian early visual system, I investigate here
      the hypothesis that congruent and conflicting stimuli are distinguished by their
      different effects on the relative timing of action potentials in primary visual
      cortex (V1), where monocular inputs are first combined. In the model, congruent
      stimulation of both eyes results in synchronization of discharges among binocular
      neurons in V1. By contrast, conflicting stimulation of the two eyes results in
      neuronal asynchrony in this area. This asynchrony then produces rivalrous
      response suppression at later stages in the visual pathway. Synchronization of
      firing in V1, however, prevents such competition, thereby ensuring non-rivalrous
      responses. These novel effects of spike timing on competition emerge naturally
      from the network dynamics. The results suggest that input-related differences in
      relative spike timing at an early stage of visual processing may play an
      important part in the phenomena both of binocular integration and rivalry;
      furthermore, they indicate that the temporal patterning of cortical activity may
      be a fundamental mechanism of selection among competing stimulus representations.

PMID- 9758219
TI  - Selective neurokinin-1 receptor antagonists are anti-hyperalgesic in a model of
      neuropathic pain in the guinea-pig.
AB  - Neuropathic pain is poorly managed by conventional analgesic therapy, such as non
      steroidal anti-inflammatory drugs and opiates. The development of animal models
      of peripheral neural damage has aided in our understanding of the pathology and
      pharmacology of neuropathic pain. This report is the first clear demonstration
      using selective neurokinin-1 receptor antagonists of a potentially novel
      therapeutic approach to the treatment of neuropathic pain resulting from
      peripheral nerve damage in a guinea-pig model. The neurokinin-1 receptor
      antagonists, SDZ NKT 343 and LY 303,870 significantly reduced mechanical
      hyperalgesia following oral and intrathecal administration. (R,R)-SDZ NK T343,
      the enantiomer of SDZ NKT 343 did not show anti-hyperalgesic activity. RPR
      100,893 showed significant anti-hyperalgesic activity only following intrathecal
      administration suggesting poor absorption or low level penetration of the blood
      brain barrier. These results imply that neurokinin-1 receptor antagonists offer a
      new class of anti-hyperalgesic drugs with a largely central site of action in
      neuropathic pain.

PMID- 9758220
TI  - Evidence for P2X3 receptors in the developing rat brain.
AB  - P2X receptor-mediated responses to the ATP analogue, alpha,beta-methylene ATP, in
      rat brain cannot be accounted for by the receptor proteins known to be present.
      Such experiments are often performed on cells from neonates and, since
      differential developmental regulation of P2X1 and P2X2 receptor messenger RNAs
      has already been demonstrated, this is likely to be the case for other P2X
      receptors. This study was designed to address the possible existence of
      alpha,beta-methylene ATP-sensitive P2X3 receptors in rat brains of various ages
      using a P2X3 receptor-selective antibody. P2X3 receptor protein was found in
      discrete regions of the embryonic (E16) and neonatal rat brain (P7 and P14) but
      was not detectable in adult animals. This is the first demonstration of the
      presence of these receptors in brains from various ages of rat and the
      differential expression of these receptors in neonates may account for some
      reported electrophysiological responses to alpha,beta-methylene ATP.

PMID- 9758221
TI  - Dynamic clamp study of Ih modulation of burst firing and delta oscillations in
      thalamocortical neurons in vitro.
AB  - The dynamic clamp technique was used in thalamocortical neurons of the rat and
      cat dorsal lateral geniculate nucleus in vitro to investigate the effects of the
      hyperpolarization-activated cation current, Ih, and of its neuromodulation on
      burst firing and delta oscillations. Specific block of endogenous Ih using 4-(N
      ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)pyridinium chloride (ZD7288)
      (300 microM) abolished the depolarizing "sag" response to negative current steps,
      markedly increased the latency and shortened the duration of the low-threshold
      Ca2+ potentials, and decreased the number of action potentials in the burst
      evoked by the low-threshold Ca2+ potential. Subsequent introduction of artificial
      Ih using the dynamic clamp re-instated the "sag" and all the original properties
      of the low-threshold Ca2+ potential. In the absence of ZD7288, introduction of
      artificial outward Ih with the intention of abolishing endogenous Ih removed the
      depolarizing "sag" and produced similar effects on the low-threshold Ca2+
      potentials as those observed during the pharmacological block of Ih. Application
      of ZD7288 to thalamocortical neurons displaying delta oscillations led to a
      reduction in the voltage range of their existence or to a complete cessation of
      this behaviour. A subsequent introduction of artificial Ih re-enabled the
      generation of delta oscillations. In the presence of ZD7288, physiologically
      relevant positive shifts in the voltage-dependence of artificial Ih increased the
      amplitude and duration of the low-threshold Ca2+ potential and increased the
      likelihood of delta oscillations while negative shifts had opposite effects.
      These results highlight the important difference between the dependence of burst
      firing and oscillations on membrane potential and their dependence on the
      properties of Ih, and demonstrate that the modulation by Ih of low-threshold Ca2+
      potentials and burst firing in thalamocortical neurons, as well as the ability of
      these neurons to generate delta oscillations, is more elaborate than previously
      described.

PMID- 9758222
TI  - The neurosteroid pregnenolone sulfate infused into the nucleus basalis increases
      both acetylcholine release in the frontal cortex or amygdala and spatial memory.
AB  - The effects of an infusion (5 ng) of the neurosteroid pregnenolone sulfate into
      the nucleus basalis magnocellularis on acetylcholine release in the
      frontoparietal cortex and basolateral amygdala were evaluated during the 130 min
      post-injection in male Sprague-Dawley rats using in vivo microdialysis coupled
      "on line" with high performance liquid chromatography detection. One week later,
      the same animals were tested for spatial memory after another infusion of
      pregnenolone sulfate (5 ng) into the nucleus basalis. Results show that
      pregnenolone sulfate enhanced acetylcholine release by more than 50% of baseline
      concentrations in the two structures relative to a control injection. The
      duration of this effect was longer in cortex (130 min) than in amygdala (30 min).
      Furthermore, pregnenolone sulfate improved memory performance in a task based
      upon spatial recognition of a familiar environment. A significant positive
      correlation (r=0.49) was found between the recognition score in the spatial
      memory test and the levels of acetylcholine release in the frontoparietal cortex
      but not in the basolateral amygdala. Therefore, our results suggest that the
      nucleus basalis magnocellularis-cortical pathway could be in part responsible for
      the promnesic effect of pregnenolone sulfate. This neurosteroid acts as a
      negative modulator of the GABA(A) receptor complex and positively modulates the N
      methyl-D-aspartate receptor, possibly resulting in a global stimulatory effect on
      central cholinergic neurotransmission.

PMID- 9758223
TI  - Insulin-like growth factor-1 ameliorates age-related behavioral deficits.
AB  - Insulin-like growth factor-1 has been found to be involved in the regulation of
      several aspects of brain metabolism, neural transmission, neural growth and
      differentiation. Because decreased insulin-like growth factor-1 and/or its
      receptors are likely to contribute to age-related abnormalities in behavior, the
      strategy of replacing this protein is one potential therapeutic alternative. The
      present study was designed to assess whether cognitive deficits with ageing may
      be partially overcome by increasing the availability of insulin-like growth
      factor-1 in the brain. Fischer-344 x Brown Norway hybrid (F1) male rats of two
      ages (four-months-old and 32-months-old) were preoperatively trained in
      behavioral tasks and subsequently implanted with osmotic minipumps to infuse the
      insulin-like growth factor-1 (23.5 microg/pump) or a vehicle, i.c.v. Animals were
      retested at two weeks and four weeks after surgery. Insulin-like growth factor-1
      improved working memory in the repeated acquisition task and in the object
      recognition task. An improvement was also observed in the place discrimination
      task, which assesses reference memory. Insulin-like growth factor-1 had no effect
      on sensorimotor skills nor exploration, but mildly reversed some age-related
      deficits in emotionality. These data indicate a potentially important role for
      insulin-like growth factor-1 in the reversal of age-related behavioral
      impairments in rodents.

PMID- 9758225
TI  - Changes in neurotransmitter release in the main olfactory bulb following an
      olfactory conditioning procedure in mice.
AB  - Olfactory learning is associated with substantial neural changes at the level of
      the accessory and main olfactory bulb, during both pheromonal learning in mated
      mice and lamb odour recognition in post partum sheep. These forms of learning
      occur during "sensitive periods" and an important question is whether similar
      neural changes occur in the olfactory bulb at other times. We used a classical
      conditioning procedure to establish an olfactory discrimination in adult mice and
      then measured changes in neurotransmitter levels in the main olfactory bulb in
      response to the presentation of the conditioned odours. Presentation of the
      conditioned, but not the non-conditioned, odour resulted in significant increases
      in the levels of certain transmitters, including glutamate from the mitral/tufted
      cells, GABA from the granule and periglomerular cells and noradrenaline from the
      centrifugal projection from the locus coeruleus. Overall, there was a decrease in
      the ratio of excitatory to inhibitory neurotransmitters in the olfactory bulb in
      response to the conditioned, but not the non-conditioned odour. Moreover, the
      magnitude of the decrease in this ratio was correlated with the level of
      behavioural response to the conditioned odour. These findings support the
      hypothesis that changes in the gain of the reciprocal synapses between
      mitral/tufted neurons and their inhibitory interneurons are a general feature of
      olfactory learning.

PMID- 9758226
TI  - In vitro long-term potentiation of electrotonic responses of goldfish mauthner
      cells is accompanied by ultrastructural changes at afferent mixed synapses.
AB  - The potentiated afferent mixed synapses of the Mauthner cells of fry and adult
      goldfish in stumps of the medulla oblongata incubated long-term in vitro were
      studied by electrophysiological and electron microscopic methods. It was shown
      that brief high-frequency stimulation of posterior branches of the eighth nerve
      induced a long-term potentiation of electrotonic transmission at large and small
      mixed club endings. It was about 135% upon subthreshold stimulation and about
      200% upon suprathreshold stimulation. The ultrastructural analysis of ultrathin
      sections of potentiated mixed synaptic endings revealed an increase in the
      dimensions of desmosome-like contacts which was proportional to the degree of
      potentiation, about 135% or 200%, depending on the type of stimulation. The
      dimensions of gap junctions remained unchanged. The dimensions of active zones at
      potentiated synapses were reduced two-fold as compared with their unpotentiated
      counterparts, irrespective of the type of stimulation. Considering that desmosome
      like contacts consist predominantly of F-actin, a molecule which possesses
      electroconductivity, it can be assumed that this cytoskeletal protein is involved
      in the process of potentiation. The increase in the synapse electrical
      conductivity can be mediated either directly, by shunting the synaptic junction
      with polymer actin filaments in the region of desmosome-like contacts, or
      indirectly, via the interaction of actin with gap junction connections situated
      nearby.

PMID- 9758224
TI  - Magnocellular vasopressinergic neurons in explant cultures are rescued from cell
      death by ciliary neurotrophic factor and leukemia inhibiting factor.
AB  - Selective death of magnocellular vasopressinergic neurons in the hypothalamus has
      been reported in cases of hereditary and idiopathic diabetes insipidus and after
      experimental lesions of the hypothalamo-neurohypophyseal pathway. To identify
      trophic factors that promote survival of these neurons, an in vitro model system
      was established in which organotypic cultures of the rat hypothalamic
      paraventricular nucleus were maintained in chemically-defined medium. We observe
      that the majority of magnocellular vasopressinergic neurons die in these
      cultures, while other cell populations such as corticotrophin-releasing factor
      producing parvicellular and oxytocin producing magnocellular cells retain a well
      preserved cytoarchitectonic organization. Degenerating vasopressinergic cells
      exhibit morphological signs of apoptosis and stained positively when analysed by
      the terminal deoxynucleotidyl transferase biotinylated dUTP nick end-labelling
      assay. Partial survival of vasopressinergic neurons occurred after co-culturing
      the paraventricular nucleus with neurohypophyseal explants, indicating that
      target-derived factors may be required for the survival of these neurons. Cell
      survival is dramatically increased by the administration of ciliary neurotrophic
      factor and leukemia inhibiting factor, but not by interleukin 6 or the members of
      the neurotrophin family. Reverse transcription-polymerase chain reaction followed
      by Southern analysis shows the presence of ciliary neurotrophic factor messenger
      RNA in the neurohypophysis. Thus, endogenous ciliary neurotrophic factor and
      leukemia inhibiting factor, produced by neurohypophyseal cells may function as a
      physiological survival factor for neurosecretory vasopressinergic neurons.

PMID- 9758227
TI  - Ultrastructural analysis reveals avoidance conditioning to induce a transient
      increase in hippocampal dentate spine density in the 6 hour post-training period
      of consolidation.
AB  - Concepts underlying memory consolidation invoke change in synapse structure and
      function. Such concepts relate to change in connectivity pattern enabled by
      increased synapse number, change in synaptic configuration resulting from
      overproduction and selective pruning, or structural change in synapse
      transmission zones. This study undertook the unbiased estimation of learning
      associated change in dendritic spine number on granule cells in the hippocampal
      dentate gyrus. Rats were trained to acquire a passive avoidance response after
      which spine number in the mid-molecular layer of the dorsal dentate gyrus were
      estimated at increasing post-training times. This showed there to be an increase
      in spine density with time after training which was initiated at 3 h, and maximal
      at 6 h. The increase at this latter time was not detected in passive control
      animals. At 72 h post-training spine density was seen to return to basal levels.
      These results are consistent with the various models for synapse connectivity
      change in memory formation whether they relate to altered number or connectivity
      pattern.

PMID- 9758229
TI  - The subcellular and cellular distribution of G protein-coupled receptor kinase 2
      in rat brain.
AB  - G protein-coupled receptor kinase 2 has been found to phosphorylate and thus
      regulate the activity of several G protein-coupled receptors implicated in
      neuronal signalling pathways. Although this kinase was initially described as a
      soluble protein, our laboratory has recently found that a significant amount of G
      protein-coupled receptor kinase 2 is associated with microsomal membranes in
      liver and different types of cultured cells. In the present report we show that
      high G protein-coupled receptor kinase 2 specific activity and protein levels are
      present in microsomal fractions of rat brain homogenates. On the other hand,
      immunochemical detection using a new antibody raised against the N-terminus of
      the kinase revealed a specific and widely distributed staining in different areas
      of the central nervous system, and the association of G protein-coupled receptor
      kinase 2 with intracellular structures in nervous cells. Our results further
      suggest that this receptor kinase may be involved in the modulation of G protein
      coupled receptor-mediated neurotransmission and that association with microsomal
      membranes may play a role in G protein-coupled receptor kinase 2 functions in the
      brain.

PMID- 9758228
TI  - Allosteric regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate
      receptors by thiocyanate and cyclothiazide at a common modulatory site distinct
      from that of 2,3-benzodiazepines.
AB  - Allosteric regulators of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate
      (AMPA) receptors include 2,3-benzodiazepines such as GYKI 52466 and GYKI 53655
      and the chaotropic anion thiocyanate that inhibit, and benzothiadiazines such as
      cyclothiazide that potentiate AMPA receptor currents. Here we sought to determine
      whether the allosteric regulators modulate AMPA receptors at a common or distinct
      allosteric sites by comparing their actions on AMPA- and kainate-evoked currents
      in cultured rat hippocampal neurons and Xenopus oocytes expressing recombinant
      AMPA receptor subunits. GYKI 52466 and thiocyanate blocked AMPA-evoked currents
      in a concentration-dependent manner (IC50 values, 8.2 microM and 1.1 mM,
      respectively); in contrast, kainate-evoked currents were blocked by GYKI 52466,
      but were potentiated by high concentrations of thiocyanate (> or = 3 mM).
      Thiocyanate enhanced the rate of desensitization and slowed recovery from
      desensitization of AMPA-evoked currents, whereas GYKI 52466 failed to affect
      desensitization. Among neurons in the hippocampal cultures, there was cell-to
      cell variability in the sensitivity to block of AMPA-evoked currents by
      thiocyanate that was correlated with the degree of potentiation by cyclothiazide.
      Moreover, cyclothiazide caused a parallel rightward shift in the concentration
      response curve for thiocyanate block, and slowed the onset of thiocyanate block
      to a rate that was similar to that of cyclothiazide dissociation. Together, these
      observations suggest that thiocyanate and cyclothiazide act at non-distinct
      allosteric sites. GYKI 52466 blocked AMPA receptor responses to a similar extent,
      irrespective of the degree of cyclothiazide potentiation. Moreover, the kinetics
      of GYKI 53655 block in the presence of cyclothiazide were not consistent with a
      competitive interaction. As is the case for cyclothiazide, SCN- exhibited greater
      affinity for flip than for flop AMPA receptor splice variants. In particular,
      GluR1flip/GluR2flip was especially sensitive to thiocyanate block. We conclude
      that thiocyanate, a flip-preferring allosteric modulator like cyclothiazide,
      appears to act by enhancing desensitization at a site that may overlap the site
      where cyclothiazide reduces desensitization, whereas 2,3-benzodiazepines act at a
      distinct site and the block does not involve a modification of desensitization.

PMID- 9758230
TI  - Oral Dyskinesias and striatal lesions in rats after long-term co-treatment with
      haloperidol and 3-nitropropionic acid.
AB  - The pathophysiologic basis of tardive dyskinesia remains unclear. It has been
      proposed that tardive dyskinesia may be a result of excitotoxic neurodegeneration
      in the striatum caused by a neuroleptic-induced increase in striatal glutamate
      release and impaired energy metabolism. To investigate this hypothesis,
      haloperidol decanoate (38 mg/kg/four weeks intramuscularly) and the succinate
      dehydrogenase inhibitor 3-nitropropionic acid (8 mg/kg/day via subcutaneous
      osmotic mini-pumps), were administered alone or together for 16 weeks to four
      months-old rats. Control rats received sesame oil intramuscularly and had empty
      plastic tubes subcutaneously. Vacuous chewing movements, a putative analogue to
      human tardive dyskinesia, were recorded during and after drug treatment.
      Haloperidol alone, 3-nitropropionic acid alone, and 3-nitropropionic
      acid+haloperidol treatments induced an increase in vacuous chewing movements.
      However, vacuous chewing movements were more pronounced and appeared earlier in
      rats treated with 3-nitropropionic acid+haloperidol. After drug withdrawal,
      increases in vacuous chewing movements persisted for 16 weeks in the haloperidol
      alone and 3-nitropropionic acid+haloperidol group and for four weeks in the 3
      nitropropionic acid alone group. Brains from each group were analysed for
      histopathological alterations. Bilateral striatal lesions were present only in
      rats with high levels of vacuous chewing movements in the 3-nitropropionic
      acid+haloperidol-treated rats. Nerve cell depletion and astrogliosis were
      prominent histopathologic features. There was selective neuronal sparing of both
      large- and medium-sized aspiny striatal neurons. These results suggest that mild
      mitochondrial impairment in combination with neuroleptics results in striatal
      excitotoxic neurodegeneration which may underlie the development of persistent
      vacuous chewing movements in rats and possibly irreversible tardive dyskinesia in
      humans.

PMID- 9758231
TI  - Characterization of the mechanism of action of tachykinins in rat striatal
      cholinergic interneurons.
AB  - The mechanism by which substance P depolarizes cholinergic interneurons in the
      rat striatum was studied using whole-cell recording techniques. In all cases the
      effects of substance P were mimicked by the neurokinin1 receptor agonist [Sar9,
      Met(O2)11] substance P and were antagonized by the neurokinin1 receptor
      antagonist SR140333. [Sar9, Met(O2)11] substance P was found to depolarize
      cholinergic interneurons by the induction of a calcium-activated inward current
      at -60 mV. This inward current was irreversibly potentiated by photolysis of
      caged GTPgammaS within neurons implicating the involvement of a G-protein. The
      [Sar9, Met(O2)11] substance P-induced inward current was inhibited by the
      phospholipase C inhibitor U-73122, and by the inclusion of the inositol-1,4,5
      triphosphate receptor antagonist heparin in the electrode solution. These
      findings suggest that neurokinin1 receptors depolarize cholinergic interneurons
      in the rat striatum primarily through a phosphoinositide signalling pathway.

PMID- 9758232
TI  - Postsynaptic nicotinic receptors on dopaminergic neurons in the substantia nigra
      pars compacta of the rat.
AB  - Previous studies have shown that application of nicotinic agonists in the
      substantia nigra pars compacta increases the firing rate of dopaminergic neurons.
      We have used intracellular recordings to show that the response of these neurons
      to nicotine is postsynaptic, since it persists in the presence of low-calcium
      buffer containing tetrodotoxin. Burst firing in the presence of nicotine was not
      observed. The presence of postsynaptic nicotinic receptors was confirmed by
      immunohistochemical localization of the alpha4 nicotinic receptor subunit on
      dendrites in the substantia nigra pars compacta. The majority of tyrosine
      hydroxylase-immunopositive neurons in the substantia nigra pars compacta were
      also immunopositive for the alpha4 subunit. Immunohistochemical localization of
      the alpha4 and beta2 subunits in adjacent brain sections produced similar
      patterns of staining. Electron micrographs clearly indicated the presence of
      alpha4 subunit at postsynaptic densities. The predominant role of nicotinic
      receptors in the central nervous system has been suggested to be the presynaptic
      modulation of neurotransmitter release [McGehee D. S. and Role L. W. (1995) A.
      Rev. Physiol. 57, 521-546]. Although several postsynaptic nicotinic responses
      have also been reported in the literature, it is unclear as to whether the
      postsynaptic nicotinic receptors mediating responses to exogenously applied
      agonists are involved in synaptic transmission. From our electrophysiological and
      immunohistochemical results, we conclude that alpha4-containing nicotinic
      receptors are found at synapses on dopaminergic neurons. These synapses are
      similar to the cholinergic synapses described at these neurons, suggesting that
      nicotinic receptors are important in modulating the excitability of dopaminergic
      neurons by direct synaptic transmission.

PMID- 9758233
TI  - Localization of 5-hydroxytryptamine1A and 5-hydroxytryptamine7 receptors in
      rabbit ocular and brain tissues.
AB  - Serotonin is thought to play a physiological role in various tissues of the
      rabbit eye, yet little is known about the relative distribution of the different
      serotonin receptors. Demonstration of the receptor subtypes present in the
      various ocular tissues is essential in order to understand the function of
      serotonin in the eye. Using a combination of in situ hybridization
      histochemistry, in vitro receptor autoradiography and polymerase chain reaction
      studies, we have explored the distribution of the 5-hydroxytryptamine1A and 5
      hydroxytryptamine7 receptors in the rabbit eye. As these receptors have not been
      sequenced in the rabbit, we initially established the suitability of the
      oligonucleotide probes by analysis of brain tissue. The distributions of 5
      hydroxytryptamine1A and 5-hydroxytryptamine7 receptor messenger RNAs in rabbit
      brain correlated well with those in other species, confirming the specificity of
      the probes for detection of the messenger RNAs in rabbit tissues. In the eye, the
      expression of 5-hydroxytryptamine1A receptors appears to be restricted to the
      epithelial cell layer of the ciliary processes, although very low levels may
      appear in the retina. In contrast, the expression of 5-hydroxytryptamine7
      receptor messenger RNA is more widespread with positive signals evident in the
      ciliary processes, retina and iris. The results confirm the existence of 5
      hydroxytryptamine1A receptors in the ciliary body and their localization in the
      ciliary epithelium supports the hypothesis that they are involved in the
      secretion of aqueous humour. Unexpectedly, there was little evidence to support
      the idea that 5-hydroxytryptamine1A receptors are present in the retina and iris
      sphincter. However, the subsequent finding of 5-hydroxytryptamine7 receptor
      messenger RNA in the retina and iris may explain the apparent absence of 5
      hydroxytryptamine1A receptors in these tissues. The presence of both 5
      hydroxytryptamine1A and 5-hydroxytryptamine7 receptors in the ciliary processes
      may account for the complex intraocular pressure response of the rabbit to
      serotonin.

PMID- 9758234
TI  - Immunolabelling of the rat intestinal tract with antibodies specific to the long
      form of the 5-hydroxytryptamine3 receptor.
AB  - The mouse 5-hydroxytryptamine3 (5-HT3) type of serotonin receptors is expressed
      as two forms, 5-HT3R-A(L) and 5-HT3R-A(S), generated by alternative splicing of
      its primary transcript, that differ by a stretch of six amino acids in the second
      intracellular loop domain. Because this six-amino acid region contains a putative
      phosphorylation site that may be important for the function and/or regulation of
      5HT3R-A(L) receptor, specifically, we developed polyclonal antibodies as
      appropriate tools for studies relevant to this question. Antibodies against a 20
      amino acid peptide corresponding to the sequence of 5-HT3R-A(L) at the level of
      this six-amino acid region were obtained as soon as one month after injection of
      this synthetic peptide to rabbits. Immunocytochemistry with these antibodies led
      to a strong positive labelling of plasma membrane, reticulum and Golgi apparatus
      of COS-7 cells expressing cloned murine 5-HT3R-A(L), whereas COS-7 cells
      expressing similar levels of 5-HT3R-A(S) exhibited only a very weak labelling.
      Immunoblots of fusion proteins combining glutathion-S-transferase and the second
      cytoplasmic loop of 5-HT3R-A(L) or 5-HT3R-A(S) revealed a c. 20-fold selectivity
      of the antibodies for the first, long form, as evaluated by densitometric
      analysis of enhanced chemiluminescence detection. Similarly, immunoblots of COS-7
      cells transfected with cloned 5-HT3 receptors showed that the anti-peptide
      antibodies detected a band at 53,000 mol. wt only in cells transfected with 5
      HT3R-A(L). Under optimal conditions, antibodies immunoprecipitated 52% of 5-HT3R
      A(L), but only 11% of 5-HT3R-A(S), solubilized from COS-7 cells transfected with
      the respective encoding plasmids. In the rat, no immunoautoradiographic labelling
      by the anti-peptide antibodies could be detected in brain structures which had
      previously been described to express preferentially a short form of the 5-HT3
      receptor. In contrast, a strong immunolabelling was found in the intestinal
      mucosa, especially in the rat fetus (at the 17th embryonic day), suggesting the
      possible participation of the 5-HT3R-A(L) isoform in the development of this
      tissue. These results show that specific antibodies are useful tools for the
      visualization of the least abundant 5-HT3 receptor isoform in rat tissue.

PMID- 9758235
TI  - Opsin localization and rhodopsin photochemistry in a transgenic mouse model of
      retinitis pigmentosa.
AB  - The VPP mouse is a transgenic strain carrying three mutations (P23H, V20G, P27L)
      near the N-terminus of opsin, the apoprotein of rhodopsin, the rod photopigment.
      These animals exhibit a slowly progressive degeneration of the rod
      photoreceptors, and concomitant changes in retinal function that mimic those seen
      in humans with autosomal dominant retinitis pigmentosa resulting from a point
      mutation (P23H) in opsin. In the present study we attempted to determine whether
      the disease process prevents the translocation of mutant opsin to the rod outer
      segments of transgenic mice, and whether it affects the photochemical properties
      of the rhodopsin present within their rod outer segments. Immunocytochemistry
      with a monoclonal antibody against a region of the C-terminus that recognizes
      epitopes common to both normal and mutant opsin (monoclonal antibody-1D4), and a
      polyclonal antibody that reacts preferentially with the mutant opsin (anti-VPP),
      were used to identify the opsin present in the rods of three-week-old VPP mice
      and normal littermates. Absorbance spectra, photosensitivity, and regeneration
      kinetics of rhodopsin in rod outer segment disc membranes were analysed by
      spectrophotometry. Western blot analysis with anti-VPP antibody indicated the
      specific binding of this antibody to the mutant opsin. Immunolocalization with
      monoclonal antibody-1D4 and anti-VPP antibodies suggested a normal translocation
      of the mutant protein to the outer segments. Aside from a small disparity in the
      absorbance spectra of rhodopsin obtained from normal and VPP retinas, there were
      no significant differences in either the ability of opsin to bind 11-cis retinal
      chromophore, or in the photic sensitivity of rhodopsin. The results indicate that
      mutant opsin is translated and incorporated into the rod outer segment disc
      membranes of VPP mice, and that the photochemical properties of rhodopsin in the
      rods of VPP retinas are similar to those of rhodopsin in normal retinas.

PMID- 9758237
TI  - The cost implications of obesity for health care and society.
AB  - The prevalence of obesity (body mass index (BMI) > 30 kg/m2) has been rising
      consistently in recent decades. Obesity is among the key promoters of a number of
      other highly prevalent and often fatal diseases. These characteristics make
      obesity one of the major cost drivers in Western health-care systems. For
      Germany, the direct costs of obesity itself are estimated to be about 850 million
      DM. Taking into account all attributable co-morbidities, the direct costs are
      estimated to be between 8.6-11.5 billion DM. If the indirect costs are also
      included in the calculations, these costs will multiply still further. There is a
      need for clinical trials in a primary care setting, in order to determine the
      impact of drug treatment (for example, sibutramine) on the treatment of obesity,
      the quality of life and the benefits of this treatment by means of a cost-benefit
      analysis (CBA) and cost-utility analysis (CUA).

PMID- 9758238
TI  - Emerging management strategies for obesity.
AB  - Management strategies for obesity, which include drug therapy, are emerging as a
      consequence of the increasing recognition of the medical seriousness of obesity.
      Obesity requires appropriate and effective management by suitably trained members
      of a multidisciplinary team, with treatment programmes putting equal importance
      on weight reduction and its maintenance. Such programmes must also take into
      account the reduction in risk from co-morbid conditions after modest weight loss
      (5-10% of initial body weight). The use of an anti-obesity drug may be justified
      for patients at risk from obesity where dietary methods, including exercise and
      behaviour modification, have failed to achieve a 10% reduction in initial body
      weight after at least three months from the start of the episode of managed care.
      Anti-obesity drugs must be prescribed in an appropriate setting, with patients
      being reviewed on a regular basis. Essential elements for managed weight loss
      include, a printed management programme, appropriate equipment, specified and
      realistic weight-loss goals, documentation of individual patient's health risks,
      and clearly defined follow-up procedures with explicit guidelines for the use of
      drugs and notification of other doctors involved in the patient's care. The
      process of drug treatment necessitates a system of regular medical audit. Many
      health-care professionals and lay persons remain sceptical about the scientific
      value of anti-obesity drugs. The emergence of increasingly specific and effective
      agents underlines the importance of ensuring appropriate use for patients at risk
      from obesity.

PMID- 9758236
TI  - Calcium channel subtypes responsible for voltage-gated intracellular calcium
      elevations in embryonic rat motoneurons.
AB  - The central role of electrical activity and Ca2+ influx in motoneuron development
      raises important questions about the regulation of Ca2+ signalling induced by
      voltage-dependent Ca2+ influx. In the purified embryonic rat motoneuron
      preparation, we recorded barium currents through voltage-activated Ca2+ channels
      using the whole-cell configuration of the patch-clamp technique. We found that
      motoneurons express at least four types of high-voltage-activated Ca2+ channels,
      based on their kinetics, voltage-dependences and pharmacological properties. Of
      the sustained Ca2+ current activated at 0 mV from a holding potential of -100 mV,
      approximately 45% was omega-conotoxin-GVIA (1 microM) sensitive, 25% was omega
      agatoxin-IVA (30 nM) sensitive and 20% was nitrendipine (250 nM) sensitive. The
      residual current, after applying these three antagonists, was an inactivating
      current that differs from classical T-type Ca2+ currents. Based on this
      pharmacology, changes in intracellular free Ca2+ concentrations were then
      monitored by Fura 2 digital imaging microspectrofluorimetry. Upon K+
      depolarization, the intracellular Ca2+ transient induced by the activation of
      each type of Ca2+ channel appeared to be quantitatively proportional to their
      Ca2+ influx. The existence of a calcium-induced calcium release mechanism through
      activation of caffeine-, ryanodine-sensitive intracellular stores was then
      investigated. High doses of caffeine and low doses of ryanodine failed to
      increase intracellular free calcium concentrations and low concentrations of
      caffeine and high concentrations of ryanodine did not affect K+-induced
      intracellular free calcium concentration transients indicating both the absence
      of Ca2+-gated Ca2+-release channels and of a Ca2+-induced Ca2+ release mechanism.
      Together, these data provide evidence that embryonic motoneurons express multiple
      Ca2+ channels that function as important regulators of intracellular Ca2+
      signalling and may be involved in their development.

PMID- 9758239
TI  - Advances in pharmacotherapy for obesity.
AB  - Anorectic drugs are increasingly being used in obesity to induce and/or maintain
      weight loss. We have focused on the development of metabolic enhancers. These
      compounds increase energy expenditure, which is important because weight loss is
      associated with metabolic re-adjustment to reduce energy output. Thus, metabolic
      enhancers ensure that energy expenditure is maintained when food intake is
      reduced. Beta3-adrenoceptor agonists are thermogenic agents that increase energy
      output by stimulating heat generation. Early selective beta3-agonists were
      effective in producing weight loss in obese rats, but were largely ineffective in
      humans. In addition, many interacted with other types of beta receptor to produce
      side-effects. The development of a Chinese hamster ovary cell (CHO) transfection
      system, using the human beta3-adrenoceptor gene, resulted in potential new
      selective human beta3-agonists being identified. However, the in vitro activity
      of these agents does not necessarily reflect their action in vivo, due to the
      presence of other receptor types and G proteins in the target cells, and
      interactions between them. The characterization of a selective beta3-antagonist,
      SR59230A, has allowed us to examine beta3-agonist activity in different
      experimental systems. The CHO transfection system has been used to show that
      SR59230A is effective in blocking agonist activity against both the rat
      adrenoceptor, and three human beta3-receptor isoforms. In addition, SR59230A
      shows competitive inhibition of agonist activity in both rat and human model
      systems. This antagonist may therefore provide a pharmacological tool for the
      functional study of by newly identified beta3-receptor agonists.

PMID- 9758240
TI  - Sibutramine: a novel anti-obesity drug. A review of the pharmacological evidence
      to differentiate it from d-amphetamine and d-fenfluramine.
AB  - Sibutramine (BTS 54 524; N-[1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutyl]-N,N
      dimethylamine hydrochloride monohydrate) is a novel 5-HT (serotonin) and
      noradrenaline reuptake inhibitor (SNRI) anti-obesity drug. Sibutramine reduces
      the food intake of rodents and this effect is partially or completely reversed by
      pretreating with 5-HT or noradrenaline antagonists, indicating that both
      neurotransmitters are involved in sibutramine's hypophagic effect. In addition,
      fluoxetine and nisoxetine, which are selective reuptake inhibitors of 5-HT and
      noradrenaline, respectively, have no effect on food intake when given alone, but
      they profoundly inhibit food intake when given in combination (equivalent to the
      actions of the SNRI, sibutramine), demonstrating a synergistic interaction of
      those two monoamines in the control of ingestive behaviour. Sibutramine reduces
      food intake by enhancing the physiological response of post-ingestive satiety.
      This reduction of food intake is a CNS-mediated effect because it is induced by
      intracerebroventricular injection of sibutramine's potently active secondary and
      primary amine metabolites (BTS 54 354 and BTS 54 505). Sibutramine increases
      energy expenditure (thermogenesis) in rats. Once again, whilst fluoxetine and
      nisoxetine have no thermogenic effect when given alone, the combination of these
      two selective monoamine reuptake inhibitors profoundly enhances thermogenesis,
      demonstrating a synergistic interaction of 5-HT and noradrenaline
      neurotransmission in the regulation of energy expenditure. Sibutramine-induced
      thermogenesis is abolished by administration of a high non-selective dose of
      atenolol or ICI 118,551 which blocks beta3-adrenoceptors in addition to beta1-
      and beta2-adrenoceptors, but not by a low dose of atenolol or ICI 118,551 which
      blocks beta1- and beta2-adrenoceptors, respectively. Glucose utilization studies
      demonstrate that sibutramine-induced thermogenesis is mediated via selective
      sympathetic activation of brown adipose tissue, and it is a centrally mediated
      effect because it is prevented by pretreating the animals with the ganglionic
      blocker, chlorisondamine. The SNRI mode of action of sibutramine is clearly
      differentiated from those of the two major classes of anti-obesity drugs, viz,
      the 5-HT releasing agents, for example, fenfluramine and dexfenfluramine, and the
      noradrenaline + dopamine-releasing agents, for example, dexamphetamine. In the
      case of the 5-HT-releasing agents, this mechanism has been linked in animal
      studies to profound and prolonged depletion and dysfunction of CNS 5-HT neurons.
      With noradrenaline + dopamine-releasing agents, it is the enhancement of central
      dopaminergic function which is believed to be responsible for their stimulant,
      rewarding and reinforcing properties and it is their releasing mechanism which
      makes them such powerful psychostimulant drugs of abuse. By utilizing
      noradrenaline and 5-HT for its anti-obesity effects, sibutramine is
      differentiated from other weight-reducing drugs which act through either 5-HT
      alone or noradrenaline + dopamine. In addition, sibutramine is further
      differentiated because it enhances monoamine function by reuptake inhibition,
      rather than by monoamine release.

PMID- 9758241
TI  - Sibutramine and energy balance.
AB  - Obesity develops from a combination of low energy expenditure and increased
      energy intake. The current treatment strategy aims at reducing energy intake by a
      low-fat, high-complex-carbohydrate diet and increasing energy expenditure by
      increased physical activity. In a major proportion of obese patients, however,
      this treatment is ineffective and does not produce a satisfactory long-term
      result. Among the risk factors for weight gain and for an unsuccessful diet
      induced weight loss in obese patients is a low metabolic rate, which can be
      attributed in part to a low sympathetic nervous system (SNS) activity. The low
      SNS activity may also have an adverse effect on appetite control. Pharmacological
      enhancement of the SNS may have a role in the normalization of the autonomic
      control of the disturbed energy balance in obesity. In animal studies,
      sibutramine causes a negative fat balance and weight loss, by a dual mechanism of
      action. Sibutramine enhances satiety by a combined noradrenergic and serotonergic
      effect, thus decreasing food intake. In addition, sibutramine stimulates
      thermogenesis by activating the SNS. Recent studies have demonstrated that
      sibutramine also enhances satiety, stimulates thermogenesis and diminishes the
      weight-loss induced decline in energy expenditure in humans, so the dual effect
      on energy balance seems to be responsible for the efficient fat loss and weight
      maintenance found in clinical trials on obese patients. In conclusion,
      sibutramine can contribute to normalization of the disturbed energy balance in
      obesity, by enhancing satiety and by the stimulation of energy expenditure.

PMID- 9758242
TI  - Sibutramine and fat distribution: is there a role for pharmacotherapy in
      abdominal/visceral fat reduction?
AB  - Visceral adiposity has a strong and independent association with obesity and its
      related co-morbidities, particularly metabolic complications such as
      cardiovascular disease and type II diabetes. Waist circumference and waist-to-hip
      ratio (WHR) are both secondary indicators of visceral obesity. This paper
      examines the effect of sibutramine, a new serotonin and noradrenaline re-uptake
      inhibitor, on weight reduction and changes in fat distribution. A meta-analysis
      of four long-term, placebo-controlled, double-blind studies showed significantly
      greater mean decreases in waist circumference in sibutramine-treated subjects
      compared with placebo (P < 0.001). Similar results were seen for WHR, with 15 mg
      sibutramine daily producing a significant reduction of 0.02 compared with placebo
      (P < 0.02). Changes in fat distribution have been examined using computerised
      tomography (CT) scans as part of the Sibutramine Trial of Obesity Reduction and
      Maintenance (STORM). Preliminary results showed a mean weight loss from baseline
      of 11.2 +/- 6.3 kg after 6 months of 10 mg sibutramine treatment. Decreases in
      total abdominal fat (18%), total subcutaneous fat (17%) and total visceral fat
      (22%) were observed, and there was a significant increase in the subcutaneous-to
      visceral fat ratio (P = 0.04). These changes in fat levels and distribution were
      associated with improvements in related risk factors such as fasting blood
      glucose and insulin levels, and blood pressure. In conclusion, sibutramine
      produces statistically and clinically significant decreases in waist
      circumference and WHR, and preferentially reduces visceral fat levels.

PMID- 9758243
TI  - Cerebral metabolic response to hypoglycemia in severe intrauterine growth
      retarded rat pups.
AB  - This study was to examine the effects of hypoglycemia on the brain metabolism of
      severe intrauterine growth retardation (IUGR) rat pups. IUGR pups were produced
      by ligating one of the uterine arteries of the dams. The pups on the opposite
      uterine horn were used as the control. They were delivered by cesarean section on
      day 21 and received regular insulin 5 units/kg or equivalent volume of normal
      saline at 40 min of age. The plasma glucose, lactate, blood gas values and brain
      glucose, lactate, ATP contents were determined at 5 and 100 min of age. The IUGR
      pups had higher plasma and brain lactate concentrations than the control
      throughout the study period. They had lower plasma glucose, oxygen and pH values,
      brain glucose and ATP contents than control at 5 min of age. Despite insulin
      induced hypoglycemia, brain ATP contents of the IUGR recovered to normal levels
      at 100 min of age when the oxygenation and pH improved. These data indicate that
      the brain energy metabolism of IUGR rat pups was suppressed by asphyxia and
      hypoglycemia. However, even in the continuing presence of hypoglycemia, brain
      energy metabolism returned to normal. The recovery is probably related to better
      oxygenation and utilization of alternative energy fuels, such as lactate.

PMID- 9758244
TI  - Prognosis following prenatal diagnosis of heart malformations.
AB  - Our objective was to document the prognosis of cases with fetal heart
      malformations (FHM). Forty-two fetuses assessed both in a regional fetal medicine
      and paediatric cardiology unit were classified prenatally into isolated FHM or
      those associated with extra-cardiac structural or karyotypic anomalies (ECA) and
      this classification was not changed subsequently (analogous to an intention to
      treat analysis). The end points studied included chromosomal abnormality,
      pregnancy outcome and follow-up at one year of age. FHM were isolated in 16 (38%)
      and associated with ECA in 26 (62%) of cases. The karyotypic abnormality rate was
      8/42 (19%) overall and 8/26 (31%) in ECA cases. The pregnancy outcome included
      termination of pregnancy in 19 (45%), intrauterine death of two (5%) and live
      birth in 21 (50%). 12/16 (75%) of isolated FHM cases were live born compared with
      9/26 (35%) of ECA cases (P < 0.03). Of the isolated FHM live born babies, 8/12
      (67%) were alive at the end of the first year and seven of these were growing
      normally and did not require cardiac medication. However, a considerable
      proportion of their first year was spent in hospital (median 8%, interquartile
      range 5-10). Only one of nine ECA live born cases was alive but with poor growth
      and dependence on cardiac drugs at one year. These data confirm previous findings
      in prenatal diagnosis series that the prognosis for FHM is worse than that
      reported in studies of congenital heart disease at birth and is strongly
      dependent upon the presence of ECA. In their absence, outcome is better than
      previously published. Counselling must take place only after full fetal medicine
      assessment and should be based upon prenatal data.

PMID- 9758245
TI  - In situ morphometric analysis of the coronary arterial growth in perinatal rats.
AB  - The perinatal changes in the diameters of left and right coronary arteries in
      rats were studied using the rapid whole body freezing technique. The main portion
      of the left coronary artery and left anterior descending and circumflex branches
      rapidly increased in diameter after birth as well as ascending aorta. The ratios
      of the diameters of the left coronary artery and anterior descending branch to
      the diameter of ascending aorta increased significantly after 4 days of age. In
      contrast, there were no significant changes in the diameter of the right coronary
      artery from the fetus to the 8-day-old pups and the ratio of the right coronary
      artery to the ascending aorta significantly decreased after birth. We report here
      that the left coronary artery in rats increases in diameter more rapidly than the
      right coronary artery in the early newborn period.

PMID- 9758246
TI  - Sleep state changes associated with cerebral blood volume changes in healthy term
      newborn infants.
AB  - In order to assess the possible effects of sleep states on cerebral haemodynamics
      in healthy term infants, we measured cerebral oxyhaemoglobin, deoxyhaemoglobin
      and total haemoglobin concentration using near infrared spectroscopy. Thirty
      seven sleep state changes in seventeen infants (gestational age: 37 to 41 4/7
      weeks), aged between two and eight days were continuously registrated during 1-3
      h. Transcutaneous PaO2, PaCO2, arterial O2 saturation and heart rate were
      simultaneously recorded and sleep states were clinically defined. There was a
      close relationship between sleep state changes and changes in total cerebral
      haemoglobin concentration, which increased from active to quiet sleep and
      decreased from quiet to active sleep. Changes in total cerebral haemoglobin were
      due, in the most part, to changes in the cerebral oxyhaemoglobin concentration.
      In conclusion, sleep states influence the cerebral haemoglobin concentration.
      Studies on cerebral haemodynamics should take sleep state into account in term
      newborn infants.

PMID- 9758247
TI  - Detection of cytokines and cytomegalovirus DNA in serum as test for congenital
      infection.
AB  - Maternal serum samples at 10 and 22 weeks of gestational age and cord blood
      samples were available from six cases of asymptomatic congenital human
      cytomegalovirus (HCMV) infection. Meaningful rises of serum IgG-antibody titers
      by ELISA occurred in three cases. Serum interferon (IFN)-gamma activity was
      detected in all six cases. Serum cell free soluble interleukin-2 receptor (sIL
      2R) activity rose above the normal range (145-519 U/ml) in one IgG and IgM
      antibody-positive and three IgG antibody-positive woman. Serum levels of sIL-2R
      and IFN-gamma were not elevated in anti-HCMV antibody-negative healthy pregnant
      women. No HCMV IE DNA was detected by PCR in the serum of any of the pregnant
      women. HCMV DNA was detected in the serum of one of six infants with asymptomatic
      congenital HCMV infection. Assessment of the changes of serum cytokines such as
      sIL-2R and IFN-gamma in HCMV antibody-positive pregnant women may be useful for
      the prenatal diagnosis of active HCMV infection during pregnancy.

PMID- 9758248
TI  - The effect of thermal stimulation on the heart-rate variability in neonates.
AB  - Thermoregulation in humans can be divided into three broad mechanisms of control,
      namely: shivering, sweating and vasomotor activity. Previous investigations
      suggested the presence of an autonomic rhythm, originating in the central nervous
      system, possibly related to thermal vasomotor control and directly affecting
      heart rate by reflex changes in cardiac sympathetic and parasympathetic activity.
      The objective of the present work was to study the maturation process of the
      thermoregulatory system in newborns. We used peripheral thermal entrainment and
      focused on the reflections of vasomotor control in the heart-rate (HR) power
      spectrum (PS). The study included three groups of neonates at three different
      ages: 10 premature infants, 6 full-terms and 7 older infants (4 to 6 months).
      Thermal stimulation was achieved by placing a hot and cold surface on the
      subject's right palm alternately at three different rates: replacing the touching
      surface every 4 s (0.25 Hz), 7 s (0.14 Hz) and 10 s (0.1 Hz). 'Double period'
      stimulation was defined as the total duration of each period of hot and cold
      stimulation at the three rates, namely 8 s (0.125 Hz), 14 s (0.07 Hz), 20 s (0.05
      Hz). The ECG of every infant was measured and recorded during the various stages
      of the experiment. The HR power spectrum from 0.02 Hz up to 2.00 Hz was
      considered, focusing on narrow ranges around the thermal stimulation frequencies.
      We found that in most subjects, clear peaks arise in the HR PS at the thermal
      entrainment frequency and its corresponding half frequency ('double period'). In
      premature infants, the reaction is best in response to the longest (10 s)
      stimulus (9 out of 10 prematures reacted positively), in group B (full-term
      infants) the reaction responds best to the 7-s stimulus (6 out of 6 reacted) and
      in older infants the reaction is slightly better at the 4-s stimulus. Since
      sympathetic control is slower, this ability to entrain the control system at
      increasing frequencies, might be related to the gradual maturation of
      parasympathetic control after birth. The different reaction of the three groups
      may help to understand the maturation process of the thermoregulation system.

PMID- 9758249
TI  - Neurodevelopmental outcome at three years of age after fetal 'brain-sparing'.
AB  - Intrauterine growth restriction (IUGR), occurring preterm, may be related to
      impaired neurodevelopmental outcome. We measured neurodevelopmental outcome
      (Hempel examination) at the age of three years in a cohort of infants born
      between 26 and 33 weeks in 1989. Fetuses were studied haemodynamically, using
      Doppler ultrasound. The ratio between the umbilical and the cerebral artery
      Pulsatility Index (U/C ratio) was calculated. This is a measure of redistribution
      of fetal blood preferentially to the brain and this may be a marker of fetal
      adaptation to placental insufficiency. Impaired fetal growth was also measured by
      the fetal growth ratio. Neonatal cranial ultrasound was performed to document
      intracranial haemorrhages and/or ischaemia. From the original cohort of 106
      infants, 96 (91%) infants were examined at three years. After adjustment for
      obstetric variables, adverse Hempel outcome was related to neonatal cranial
      ultrasound abnormality and low head circumference at three years. Neither the U/C
      ratio nor fetal growth were independently associated with Hempel outcome. Fetal
      'brain-sparing' in IUGR appears to be a benign adaptive mechanism preventing
      severe brain damage.

PMID- 9758250
TI  - Cardiac regression sequence: reversal of blood flow is diagnostic but not
      causative in an acardiac fetus.
AB  - In 1% of monozygotic twin pregnancies, one fetus is without a heart; blood
      circulation is maintained by an accompanying "pump" twin. Such an acardiac
      condition is usually diagnosed on the basis of further malformations visible by
      ultrasonography. We describe a monoamniotic twin pregnancy with early growth
      reduction in one twin. His skeleton and the shape of the body including the head
      were normal; however, heart, lungs and liver were absent. "Death of one twin" had
      thus been the diagnosis before termination of pregnancy. Studies of the blood
      flow in acardiac fetuses by several investigators have shown that perfusion of a
      heartless fetus is opposite to the normal direction and the term "twin reversed
      arterial perfusion sequence" has been proposed. While "reversed arterial
      perfusion" might be a key diagnostic element for the ultrasonographic examination
      of the acardiac condition, it need not necessarily be the primary cause. A lethal
      defect in early heart development is much more likely to be the primary event
      which is temporarily rescued by the presence of the accompanying "pump" twin. A
      term like "cardiac regression sequence" would be much better suited to describe
      the condition.

PMID- 9758251
TI  - Lactate, lactate/pyruvate ratio and catecholamine interrelations in cord blood at
      delivery in complicated pregnancies.
AB  - The interrelationships between lactate, lactate/pyruvate (L/P) ratio and
      catecholamines (CA) in cord artery and vein blood were studied in 56 pregnancies
      who had complications in the antenatal period or during labour. This group of
      babies had higher CA levels and were more acidaemic than fetuses after normal
      pregnancies and labour. There were stronger correlations between lactate and
      noradrenaline (NA) (R = 0.56, P < 0.001), adrenaline (A) (R = 0.41, P = 0.002)
      and dopamine (DA) (R = 0.42, P = 0.001) in cord artery blood, than previously
      reported for normal deliveries. Correlations between L/P ratio and CAs were also
      significant, although weaker. Multiple regression analysis, using cord artery
      lactate as the dependent variable, revealed significant correlations for pH (P =
      0.01) and pyruvate (P < 0.001) but not for the CAs. The subgroups with high
      lactate (> 75th centile) had significantly higher NA (P = 0.007) and DA (P <
      0.001) in cord artery and NA (P < 0.001) and A (P < 0.001) in cord vein blood, as
      compared with the subgroup who had lower lactate concentrations. We conclude that
      fetal hypoxia induces fetal CA production as well as anaerobic metabolism with
      lactate production. However, the adrenergic stimulation seems not to contribute
      significantly to the fetal lactate production.

PMID- 9758252
TI  - Aspects of malignant progression of vulvar epithelial disorders.

PMID- 9758253
TI  - Hysterectomy: indications, surgical routes, cases for adnexal or cervical
      conservation.

PMID- 9758254
TI  - Hypertrophic cardiomyopathy and pregnancy.
AB  - The case of a young primiparous woman with defibrillator-assisted familial
      hypertrophic cardiomyopathy (HCM) has led us to review the literature on this
      pathology, which is exceptional because of its scarcity and the originality of
      the problems encountered. To our knowledge, this is the first observation ever
      reported of defibrillator-assisted activation during pregnancy in a woman with
      HCM. Several questions raised from this particular case, e.g. what are the risks
      caused by pregnancy in these patients, what is the impact of therapeutics, does
      the activation of an internal defibrillator involve particular risks, what is the
      best disposition for delivery and what are the risks for fetuses? We have tried
      to ask all of these questions, using as exhaustive a literature review as
      possible.

PMID- 9758255
TI  - Urolithiasis in pregnancy--a clinical challenge.
AB  - Symptomatic urolithiasis in pregnancy is a rare event. We present a series of 13
      cases. Although controversial, we think that X-rays should be avoided if
      possible. Ultrasound may not be the perfect diagnostic tool in every case of
      stone disease, however in pregnancy it is the imaging of choice and led to an
      accurate diagnosis in all our cases. Thirty-eight percent of the patients were
      managed conservatively throughout their pregnancy, and another thirty-eight
      percent of our patients needed more extended treatment but could be managed by
      simple insertion of a double J ureteric stent (DJ). Therefore, in our series
      invasive treatment was not necessary in the majority of patients. Each one
      patient required a percutaneous nephrostomy (PCN) and a nephrectomy for a non
      functional pyonephrotic kidney. Urolithiasis in pregnant women constitutes a
      challenge for the treating urologists since they are deprived of some of their
      essential tools, such as X-rays and extracorporeal shock wave lithotripsy (ESWL),
      and since normally tolerable complications of less invasive treatments can have
      disastrous consequences in pregnant patients. Therefore, decisions on any kind of
      treatment have to be made very prudently and critically. We present an algorithm
      for the management of stones in pregnancy which may be helpful in decision
      making.

PMID- 9758256
TI  - Relevance of serum bile acid profile in the diagnosis of intrahepatic cholestasis
      of pregnancy in an high incidence area: Portugal.
AB  - OBJECTIVE(S): The present work was conducted to clarify the relevance of usual
      liver function tests, and define the most predictive serum bile acid profile for
      diagnosis of intrahepatic cholestasis of pregnancy (ICP). STUDY DESIGN: This
      study comprised 20 healthy nonpregnant women and 77 pregnant women in the last
      trimester of pregnancy, from which 38 were normal pregnancies, and 39 suffered
      from ICP. Liver function tests were evaluated by routine laboratory techniques,
      conjugated bile acids were analysed by high-performance liquid chromatography,
      and unconjugated forms were measured by an enzymatic-fluorimetric assay. RESULTS:
      During the third trimester in normal pregnancy, increased concentration of
      conjugated species affected all primary bile acids, although only significantly
      for glycocholic acid. Moreover, deoxycholic acid proportion decreased when
      compared with healthy nonpregnant women. Important ICP-induced changes in serum
      profiles of amidated bile acids were observed, involving both a marked increase
      in cholic acid concentration and a shift towards a higher proportion of taurine
      conjugated species. Among routine liver tests, alanine aminotransferase and
      conjugated bilirubin were the most common indicators of ICP. CONCLUSION(S): In
      the early diagnosis and follow-up of ICP, the most predictive and accurate
      markers (efficiency 100%) were: (i) TBA concentration in serum >11.0 micromol(
      1): (ii) cholic/chenodeoxycholic acid ratio >1.5 and cholic acid percentage >42%:
      (iii) glycine/taurine bile acid ratio <1.0 or glycocholic acid concentration >2.0
      micromol(-1). Accurate diagnosis based on sensitive biochemical markers followed
      by appropriate treatment may improve both pregnancy outcome and newborn
      prognosis.

PMID- 9758257
TI  - Maternal and fetal plasma concentrations of endothelin, lipidhydroperoxides,
      glutathione peroxidase and fibronectin in relation to abnormal umbilical artery
      velocimetry.
AB  - OBJECTIVE: To study plasma concentrations of endothelin (ET), lipidhydroperoxides
      (LOOH), glutathione peroxidase (GSHpx) and fibronectin in relation to abnormal
      umbilical artery velocimetry. STUDY DESIGN: Plasma concentrations of ET, LOOH,
      GSHpx and fibronectin were measured in fetal and maternal venous blood in: (i) a
      control group (n=10); (ii) in pregnancies complicated by intrauterine growth
      retardation (IUGR) (n=6) or preeclampsia (n=5) with positive end diastolic flow;
      and in (iii) pregnancies complicated by absent or reversed end diastolic (ARED)
      flow in the umbilical artery (n=18). All children were delivered by primary
      caesarean section. RESULTS: The significantly highest maternal and fetal ET
      concentrations were found in plasma collected in pregnancies complicated by ARED
      flow in the umbilical artery. Maternal fibronectin levels were significantly
      raised in the ARED flow group. Maternal plasma ET levels were lowest in
      pregnancies complicated by IUGR. The maternal and fetal plasma concentrations of
      LOOH and GSHpx did not differ significantly between the groups. CONCLUSION:
      Abnormal Doppler velocimetry, especially ARED flow is associated with elevated
      maternal and fetal plasma levels of ET. The exact mechanism causing the placental
      vasoconstriction is unknown yet, but oxidative stress seems not to be involved.

PMID- 9758258
TI  - A prospective study of persistent back pain after pregnancy.
AB  - OBJECTIVES: To determine the prevalence of back pain after delivery and its
      relationship to individual factors. STUDY DESIGN: A cohort of 88 pregnant women,
      aged 14-46 years, who had suffered from back pain during pregnancy, and delivered
      at Aydin Maternity Hospital was selected. They had been followed up through
      pregnancy, and 6 months post partum filled out a questionnaire. The data were
      analyzed statistically. RESULTS: Follow-up showed that back pain at the time of
      delivery and 6 months post partum was reported by 59.1% and 43.2% of the women,
      respectively. The difference in prevalence of back pain between young women and
      older ones was statistically significant (P=0.000). The number of previous
      pregnancies increased the risk of back pain (P=0.000), but there was no
      difference in prevalence of back pain between women with heavy work and without
      heavy work before pregnancy (P=0.310). Furthermore, women with a history of back
      pain before pregnancy were found to experience more intense pain at 6 months post
      partum compared to those without a history of back pain before pregnancy (2.1+/
      1.0 and 0.4+/-0.4. respectively. P=0.000). CONCLUSION: These results indicate
      that pregnant women with a previous history of back pain had a higher prevalence
      of back pain, especially in young multigravid patients.

PMID- 9758259
TI  - Low-molecular-weight heparin combined with aspirin in pregnant women with
      thrombophilia and a history of preeclampsia or fetal growth restriction: a
      preliminary study.
AB  - OBJECTIVE: To assess the prevalence of haemostatic abnormalities in patients with
      an obstetric history of preeclampsia and/or fetal growth restriction and
      documented thrombophilia, and to evaluate the effects of low-molecular-weight
      heparin (LMWH) and aspirin on pregnancy outcome. METHOD: A total of 276 patients
      with a history of preeclampsia and/or fetal growth restriction were tested for
      the presence of coagulation abnormalities and anticardiolipin antibodies (ACA).
      Ninety patients with preeclampsia and 15 patients with isolated fetal growth
      restriction had haemostatic abnormalities. Twenty-six patients with coagulation
      abnormalities: protein S-deficiency, activated protein C (APC) resistance and/or
      > or =15 ACA GPL and/or MPL had a subsequent pregnancy and were treated with
      aspirin in combination with LMWH. Their pregnancy outcome was compared with all
      patients having a subsequent pregnancy from the same cohort without
      abnormalities, or <15 ACA GPL and/or MPL who received aspirin (n=19). RESULTS: In
      subsequent pregnancies birth weight of babies born to patients with an
      unequivocal coagulation abnormality (i.e., protein S-deficiency, APC resistance,
      or ACA titres > or =15 GPL and/or MPL), were higher than in the group with no
      disorders or <15 ACA GPL and/or MPL (P=0.019). CONCLUSIONS: In this preliminary
      study, LMWH appears to have a favourable effect on the pregnancy outcome of women
      with a history of preeclampsia and/or fetal growth restriction and documented
      thrombophilia. Randomised trials are required.

PMID- 9758260
TI  - Contribution of congenital malformations to perinatal mortality. A 10 years
      prospective regional study in The Netherlands.
AB  - OBJECTIVE: : To determine the precise contribution of congenital malformations to
      perinatal mortality in a region. DESIGN: Prospective, descriptive. SETTING:
      Region, Delft-Westland-Oostland (DWO) in the Netherlands. MATERIAL AND METHODS:
      The registration was based on data concerning all deliveries of women domiciled
      in the health region DWO of the Netherlands. The incidence and contribution of
      congenital malformations to perinatal death was evaluated by a team consisting of
      a gynaecologist. a paediatrician and a paediatric pathologist. Malformations were
      classified as lethal or nonlethal and recorded separately for stillbirth (from 28
      weeks gestation) and liveborn infants with 7-day follow-up. RESULTS: In 10 years
      (1993-1992) 28983 children were born in the region DWO. The perinatal mortality
      was calculated as 247 cases (0.85%). The overall incidence of congenital
      malformations in the perinatal death-group was 33%. Lethal congenital
      malformations were found in 51% of the cases in the stillbirth-group and 70% of
      the cases in the neonatal death-group. Congenital malformations of the central
      nervous system are mostly lethal in the stillbirth-group (45%). Cardiovascular-
      and pulmonary-defects were more prominent in the neonatal period (27% and 33%
      respectively of the neonatal deaths). Uro-genital and minor malformations
      (miscellaneous) are more often seen in perinatal deaths without being a
      contributor to the cause of death. CONCLUSIONS: As most congenital malformations
      are multifactorial in origin, it is in the understanding and control of such
      conditions that efforts and resources should now be turned. Through a detailed
      postmortem fetal and placental examination and clinical-pathological correlations
      lethal congenital malformations were found in 51% in stillbirths (mainly central
      nervous system) and 70% in neonates (mainly cardiovascular and pulmonary
      defects).

PMID- 9758261
TI  - Vitamin B12 levels in pregnancy influence erythropoietin response to anemia.
AB  - OBJECTIVE: to discover whether vitamin B12 levels influence erythropoietin (EPO)
      response during pregnancy. STUDY DESIGN: 117 pregnant women after the 27th week
      were divided into three groups according to log vitamin B12 concentrations. EPO
      (by enzyme-linked immunosorbent assay), Hemoglobin (Hb) and medium corpuscular Hb
      concentration (MCHC) were measured in these patients. The tests used were:
      calculation of simple statistic, regression coefficient and t-independent test
      with level of significance. An exclusive partitioned cluster method (K-means
      procedure) was used. RESULTS: For the lowest vitamin B12 levels there is an
      unexpected lack of difference in plasma EPO levels between anemic and nonanemic
      patients. In fact EPO levels were high even in nonanemic women. The only
      parameter of the blood count that seems to change in relation to vitamin B12
      concentration is the MCHC. CONCLUSIONS: These results suggest that low vitamin
      B12 levels inhibit the suppression of EPO response in nonanemic pregnant women
      probably through MCHC modifications.

PMID- 9758262
TI  - Cervicovaginal fetal fibronectin concentrations: predictive value of impending
      birth in postterm pregnancies.
AB  - OBJECTIVE: To determine the predictive value of cervicovaginal fetal fibronectin
      (fFN) concentrations > or =50 ng/ml for spontaneous onset of labour within 3 days
      in pregnancies of 41 weeks gestation or more. STUDY DESIGN: In the Department of
      Obstetrics, Leiden University Medical Centre, and of the Diaconessen Hospital,
      Voorburg (The Netherlands), 126 cervicovaginal secretions of fFN, from 80
      consenting women between 287 and 304 days gestation were collected. Pregnant
      women underwent sterile speculum examinations for cervicovaginal sampling from
      the 41st week onwards. The fFN concentration in these samples was determined with
      a quantitative solid-phase enzyme-linked immunosorbent assay. Concentrations of
      <50 ng fFN per ml were characterised as negative test results, meaning that
      spontaneous delivery would not take place within 3 days, and those of > or =50
      fFN ng/ml were taken as positive test results. Sensitivity and specificity of the
      fFN test were calculated for predicting spontaneous birth. Parametric and
      nonparametric tests were used for evaluating differences and correlations.
      RESULTS: Spontaneous delivery took place after 2.5+/-2.5(SD) days with fFN values
      > or =50 ng/ml and after 4.7+/-3.6 days with fFN concentrations <50 ng/ml
      (P<0.001). Sensitivity and specificity of the fFN test predicting spontaneous
      onset of labour within 3 days, were 0.71 [95% confidence interval (CI) 0.58-0.86]
      and 0.64 (95% CI 0.48-0.78). If fFN > or =50 ng/ml then a spontaneous onset of
      labour is more likely to occur within 3 days (odds ratio 4.5 (95% CI 1.8-11.3).
      CONCLUSIONS: The fFN test does not predict accurately enough whether or not birth
      will take place within 3 days of sampling. Nevertheless, the higher odds for
      spontaneous delivery within a few days when the test is positive may be of use in
      planning adjusted induction of labour.

PMID- 9758263
TI  - Malignant fibrous histiocytoma of the stomach during pregnancy: a case report.
AB  - In this case report we describe a patient with a primary malignant fibrous
      histiocytoma of the stomach, diagnosed and operated upon during the sixth month
      of pregnancy. We stress the importance of a thorough diagnostic examination in
      cases of severe anaemia during pregnancy. Although very rare, malignancy of the
      gastrointestinal tract should be taken in consideration. No holding back is
      justified in diagnostic and therapeutic measurements because of pregnancy.
      Radiologic examination of the gastrointestinal tract should be replaced by
      endoscopy.

PMID- 9758264
TI  - Epileptogenic activity of folic acid after drug induces SLE (folic acid and
      epilepsy)
AB  - OBJECTIVE: To study the effect of folic acid-containing multivitamin
      supplementation in epileptic women before and during pregnancy in order to
      determine the rate of structural birth defects and epilepsy-related side effects.
      STUDY DESIGN: First a randomised trial, later periconception care including in
      total 12225 females. RESULTS: Of 60 epileptic women with periconceptional folic
      acid (0.8 mg)-containing multivitamin supplementation, no one developed epilepsy
      related side effects during the periconception period. One epileptic woman
      delivered a newborn with cleft lip and palate. Another patient exhibited with a
      cluster of seizures after the periconception period using another multivitamin.
      This 22-year-old epileptic woman was treated continuously by carbamazepine and a
      folic acid (1 mg)-containing multivitamin from the 20th week of gestation. She
      developed status epilepticus and later symptoms of systemic lupus erythematodes.
      Her pregnancy ended with stillbirth. CONCLUSIONS: The epileptic pregnant
      patient's autoimmune disease (probably drug-induced lupus) could damage the blood
      brain barrier, therefore the therapeutic dose (> or =1 mg) of folic acid
      triggered a cluster of seizures. Physiological dose (<1 mg) of folic acid both in
      healthy and 60 epileptic women, all without any autoimmune disease, did not
      increase the risk for epileptic seizures.

PMID- 9758265
TI  - Within-subject variability of differences between conventional and automated
      blood pressure measurements in pregnancy.
AB  - OBJECTIVE: To determine whether measured differences between standard mercury
      sphygmomanometry and the SpaceLabs 90207 ambulatory blood pressure monitor in
      pregnant women remain constant during 24 h measurements. STUDY DESIGN: Repeated
      comparisons between standard mercury sphygmomanometry and Spacelabs 90207 were
      performed at nine predetermined time points during 24 h ambulatory blood pressure
      measurements in a group of ten pregnant women with various pregnancy
      complications, including hypertension. Individual and group differences between
      standard mercury sphygmomanometry and SpaceLabs 90207 were calculated for each
      time point. Friedman's ANOVA was used to test stability of differences across
      time. RESULTS: Mean group differences (standard deviation) between mercury
      sphygmomanometry and the SpaceLabs 90207 were -2 (6) mmHg and 3 (7) mmHg for
      systolic and diastolic pressure respectively. For systolic pressure the
      differences between time points were not statistically significant. Although a
      statistical significant trend was found for diastolic pressure differences
      (P<0.05), none of the contrasts between any pair of time points reached
      statistical significance. For both systolic and diastolic pressure the minimal
      and maximal difference lay at least 10 mmHg apart in seven patients. CONCLUSIONS:
      Despite standardisation and training, a substantial within-subject variability of
      the pressure difference between observers and SpaceLabs was found in this
      heterogeneous group of women. However, a systematic time-related effect on this
      pressure difference could not be demonstrated. The pressure difference between
      both methods cannot be estimated with great precision. This is a serious
      impediment for the clinical interpretation of automated or ambulatory blood
      pressure data.

PMID- 9758266
TI  - Pregnancy outcome after repeated blunt abdominal trauma.
AB  - During a four-year period, five of 49671 parturients were admitted on a
      prospective study protocol for repeated direct blunt abdominal trauma due to
      falls during pregnancy. Preterm contractions were noted in three patients one of
      which delivered preterm. No delayed abruptio placentae, intrauterine growth
      restriction or antepartum death were encountered. All patients delivered
      spontaneously. Repeated blunt abdominal trauma occurs rarely in pregnancy.
      Routine hospitalised surveillance in the absence of vaginal bleeding or uterine
      contractions may not be warranted.

PMID- 9758268
TI  - Bilateral ureteric obstruction following vaginal hysterectomy: oedema of the
      bladder can be a rare cause.
AB  - Known causes of bilateral ureteric obstruction following vaginal hysterectomy and
      vaginal wall repair are accidental bilateral ureteric ligation and kinking of the
      ureters. A case of bilateral ureteral obstruction due to bladder wall oedema is
      presented. A cause for this extreme oedematous reaction was not found. Post-renal
      obstruction does not necessarily result in dilatation of the ureters, therefore
      ultrasound cannot always be used to exclude a post-renal obstruction.

PMID- 9758267
TI  - An anatomical classification--a new paradigm for management of female lower
      urinary tract dysfunction.
AB  - A new anatomical classification specifies anatomical defects in the anterior,
      middle and posterior zones of the vagina as the cause of female lower urinary
      tract dysfunction. An external musculoelastic mechanism stretches the vagina to
      open and close the outflow tract. The same pelvic floor muscles provide a
      peripheral control mechanism for micturition. The stretched vagina prevents the
      filling bladder from activating the stretch receptors in the bladder neck.
      Vaginal laxity may weaken transmission of muscle forces, interfering with
      urethral opening and closure, a mechanical process. Laxity may also destabilize
      the peripheral control mechanism, a neurological process, causing bladder control
      to swing between the open and closed modes urodynamically interpreted as bladder
      instability. Specific symptoms, signs, and urodynamic tests can be arranged into
      a pictorial algorithm. This acts as a practical guide for locating the three
      zones of anatomical defects. It has been possible to reinterpret almost all the
      definitions and descriptions of the International Continence Society (ICS) in
      terms of this classification, and to explain how vaginal laxity may cause
      premature activation of the micturition reflex (detrusor instability), stress
      incontinence and abnormal emptying (dribble, overflow). This convergence in
      anatomical and urodynamic (ICS) concepts explains many previously unexplained
      phenomena, and potentially opens up a new approach to management, nonsurgical
      strengthening of specific ligaments, or surgical reinforcement thereof with
      ambulatory "microinvasive" methods which do not require catheterization.

PMID- 9758269
TI  - Biochemical hemodynamic and hematological changes during transcervical resection
      of the endometrium using 1.5% glycine as the irrigating solution.
AB  - OBJECTIVE: To study fluid absorption during transcervical resection of the
      endometrium (TCRE) and its effect on the biochemical, hemodynamic and
      hematological alterations so that life threatening complications of fluid
      overload may be prevented. METHOD: Intraoperative fluid (1.5% glycine) absorption
      in 46 women undergoing TCRE was studied and correlated using biochemical
      parameters (serum sodium, potassium, total proteins, creatinine and blood urea),
      hemodynamic parameters (pulse rate, blood pressure, oxygen saturation and end
      tidal CO2) and hematological parameters. Twenty five of these patients had
      received danazol (800 mg/day) for six weeks prior to TCRE. RESULT: The mean
      glycine deficit during TCRE was found to be 474.45 ml, with a mean total inflow
      of 3802.17 ml. Amongst all of the parameters, only serum sodium levels were found
      to be significantly inversely correlated with the glycine deficit. No case of
      hyponatremia occurred below a deficit of 1000 ml. Severe hyponatremia was
      reported in three cases (6.4%) and all three had a glycine deficit of more than
      1000 ml. No case of pulmonary edema was noted. The mean glycine deficit was
      significantly lower (P=0.007) and the duration of procedure significantly shorter
      (P=0.0009) in the patients who had received danazol. None of the patients in the
      danazol group had fluid absorption of more than 1000 ml. CONCLUSION: Close
      monitoring of fluid inflow and outflow should be done during TCRE. Above a
      deficit of 1000 ml, serum sodium should be measured to detect significant
      hyponatremia. The use of danazol for endometrial preparation also reduces the
      mean amount of fluid absorbed.

PMID- 9758270
TI  - Benign intracardiac teratoma detected prenatally. Case report and review of the
      literature.
AB  - Primary cardiac tumors are rare and, until recently, were mostly incidental
      postmortem findings. Nowadays, due to the widespread use of prenatal ultrasound
      scans, we are able to diagnose them in utero. We present a case of an
      intracardiac teratoma diagnosed at 38 weeks, menstrual age. Previous scans had
      been normal. Labor was induced, and a female infant with an Apgar score of 9 and
      4, at 1 and 5 min, was delivered. Her condition worsened rapidly. She died 16 h
      after birth. Necropsy was performed, and a cystic, mature teratoma of 4 cm was
      found in the interventricular septum, growing into the right ventricle. No other
      anomalies were found. This probably represents the first case of an intracardiac,
      benign teratoma diagnosed prenatally.

PMID- 9758271
TI  - Early detection of caudal regression syndrome: specific interest and findings in
      three cases.
AB  - Caudal regression syndrome (CRS) is a rare malformative syndrome seen mainly in
      cases of maternal diabetes with poor metabolic control. Early detection by
      vaginal ultrasound is possible. The authors describe three cases of CRS, relating
      the characteristic ultrasound findings which include abrupt interruption of the
      spine at the dorsal or lumbar level and abnormal position of the lower limbs. The
      femur bones are fixed in a 'V' pattern, giving a typical 'Buddha's poise'.

PMID- 9758272
TI  - The seventh meeting and exchange programme of European Obstetricians and
      Gynaecologists in training (13-15 November, 1997, in Athens).
AB  - The European Network of Trainees in Obstetrics and Gynaecology (ENTOG) is a newly
      founded organisation which is closely associated with the European Board and
      College of Obstetrics and Gynaecology. The main objectives of ENTOG are: (i) to
      provide a forum for trainees to discuss and express their opinions on issues in
      Obstetric/Gynaecology (Ob/Gyn) training; (ii) to establish a continuous means of
      communication between European trainees; (iii) to promote high standards of
      training and thus improve the quality of medical care. To reach these objectives,
      ENTOG organizes a yearly exchange programme and educational meeting for trainees.
      Recently, a meeting was held in Greece with harmonization of training programmes
      in Ob/Gyn serving as a main topic.

PMID- 9758273
TI  - Clinical evaluation of a commercial ligase-based gene amplification method for
      detection of Mycobacterium tuberculosis.
AB  - The purpose of this study was to evaluate the clinical usefulness of a commercial
      ligase-based gene amplification method (LCx Mycobacterium tuberculosis test;
      Abbott Laboratories, USA) for detection of Mycobacterium tuberculosis. The
      tuberculosis infection rate among clinical samples was 10.6%. The sensitivity,
      specificity, and positive and negative predictive values were 23.5%, 100%, 100%,
      and 91.7%, respectively, with the fluorochrome auramine stain; 32.4%, 100%, 100%,
      and 92.6%, respectively, with culture; and 76.5%, 95.8%, 68.4% and 97.2%,
      respectively, with the gene amplification method. When only samples from patients
      without current or previous treatment were studied, the sensitivity was 36.4%
      with the auramine stain, 63.6% with culture, and 100% with the gene amplification
      assay. The mean treatment time for culture-negative and assay-negative samples
      was greater than that of culture-negative and assay-positive samples. The LCx
      Mycobacterium tuberculosis test is a sensitive method for detection and
      identification of Mycobacterium tuberculosis. It produces few false-positive
      results. However, as it can remain positive after the culture becomes negative,
      it is not recommended for evaluation of treatment efficiency.

PMID- 9758274
TI  - Bacteraemia in the adult intensive care unit of a teaching hospital in
      Nottingham, UK, 1985-1996.
AB  - Bacteraemia is an important cause of morbidity and mortality in the intensive
      care unit. In this study the distribution of organisms causing bacteraemic
      episodes in patients in the adult intensive care unit of a large teaching
      hospital was determined. Particular emphasis was placed on the type of organisms
      isolated from community- and hospital-acquired bacteraemia, the suspected source
      of infection, the possible risk factors associated with bacteraemia, and outcome.
      The incidence of bacteraemia and fungaemia increased from 17.7 per 1000
      admissions in 1985 to 80.3 in 1996. A total of 315 episodes of bacteraemia and
      fungaemia were documented over a 12-year period, of which 18% were considered
      community-acquired and 82% hospital-acquired. Gram-positive and gram-negative
      bacteria accounted for 46.9% and 31.5% of the episodes, respectively.
      Polymicrobial infection accounted for 17.8% and fungi for 3.8% of the episodes.
      Staphylococcus aureus (22.5%), Staphylococcus epidermidis (7.6%), and
      Streptococcus pneumoniae (7.9%) were the predominant gram-positive bacteria
      implicated, whereas Escherichia coli (6%), Enterobacter cloacae (7%), Klebsiella
      aerogenes (3.8%), Pseudomonas aeruginosa (5.1%), and Acinetobacter spp. (3.8%)
      were the predominant gram-negative bacteria isolated. The two most common sources
      of infection were the respiratory tract (39.7%) and an intravascular line
      (24.5%), but in 8.9% of episodes the focus of infection remained unknown.
      Bacteraemic patients stayed in the unit for a longer period (12 days) than did
      non-bacteraemic patients (3 days). The overall mortality related to bacteraemia
      and candidaemia was 44.4%. Surveillance of bacteraemia in the intensive care unit
      is important in detecting major changes in aetiology, e.g., the increasing
      incidence of gram-positive bacteraemia, the emergence of methicillin-resistant
      Staphylococcus aureus in 1995, and the emergence of Enterobacter cloacae. It is
      of value in determining empirical antimicrobial therapy to treat presumed
      infection pending a microbiological diagnosis and in directing the development of
      guidelines for infection prevention, e.g., guidelines for central venous catheter
      care.

PMID- 9758275
TI  - Antibiotic resistance in Salmonella enterica serotype typhimurium.
AB  - In order to analyse the development of antibiotic resistance in Salmonella spp.,
      a total of 262 Salmonella strains isolated in 1987 (n = 148) and in 1996 (n =
      114) from clinical specimens in Wurzburg, Germany, were tested in parallel by the
      agar diffusion method. In 1987. most of the strains were Salmonella enterica
      serotype typhimurium (42.6%), whereas in 1996 most were Salmonella enterica
      serotype enteritidis (68.4%). The majority of Salmonella enterica serotype
      enteritidis isolates was fully susceptible in 1987 and 1996. In contrast, the
      percentage of drug-resistant strains of Salmonella enterica serotype typhimurium
      increased significantly from 27% in 1987 to 52.4% in 1996. This increase, which
      might reflect uncontrolled use of antibiotics in the environment, should be of
      concern to public health authorities.

PMID- 9758276
TI  - Radiometric quantification of Mycobacterium avium complex.
AB  - The purpose of this study was to establish a system that would allow rapid and
      reliable quantification of Mycobacterium avium complex infection with a method
      that was as sensitive as counting of colony-forming units but less time-consuming
      and safer in the laboratory. The radiometric system for quantification of
      mycobacteria (Bactec, Becton Dickinson, USA) which calculates growth curves, was
      found to be faster, safer, and as sensitive as the established method of counting
      colony-forming units, with a low intra-assay variation and a wide assay range.
      Furthermore, the calculated growth curves provided important additional
      information about replication characteristics of the mycobacteria.

PMID- 9758277
TI  - Comparison of three media for agar dilution susceptibility testing of Bordetella
      pertussis using six antibiotics.
AB  - Since antimicrobial susceptibility testing of the fastidious species Bordetella
      pertussis is not standardized, the most suitable medium for agar dilution testing
      of this species has not yet been determined. In the present study, Mueller
      Hinton, Bordet-Gengou, and Oxoid charcoal agars (each supplemented with 5% horse
      blood) were evaluated for agar dilution susceptibility testing of Bordetella
      pertussis against ampicillin, chloramphenicol, ciprofloxacin, doxycycline,
      erythromycin, and trimethoprim-sulfamethoxazole. Mueller-Hinton agar was the most
      suitable medium.

PMID- 9758279
TI  - In vitro activity of mupirocin against methicillin-resistant Staphylococcus
      aureus isolated from a hospital in Spain.

PMID- 9758280
TI  - Urinary tract infection due to Arcanobacterium bernardiae in a patient with a
      urinary tract diversion.

PMID- 9758278
TI  - Non-tuberculous mycobacterial infection in children with cancer.
AB  - Reported here is the clinical presentation and management of patients with
      rapidly growing non-tuberculous mycobacterial infection diagnosed in a paediatric
      oncology unit. A retrospective analysis that correlated patient isolates with the
      children's cancer registry revealed two cases of non-tuberculous mycobacterial
      infection; both had been observed within the last 6 years and were due to
      Mycobacterium chelonae. The first case was line-associated and the second was a
      disseminated infection. In both cases the patients were lymphopenic and had had
      indwelling vascular catheters. Neither patient was neutropenic. The literature on
      mycobacterial infection in children with cancer is also reviewed.

PMID- 9758281
TI  - Association between quinupristin/dalfopristin resistance in glycopeptide
      resistant Enterococcus faecium and the use of additives in animal feed.

PMID- 9758282
TI  - Trovafloxacin: in vitro activity, pharmacokinetics, and clinical experience.
      Introduction.

PMID- 9758283
TI  - Bacteriological activity of trovafloxacin, a new quinolone, against respiratory
      tract pathogens.
AB  - The use of established fluoroquinolones, such as ciprofloxacin and ofloxacin, as
      empirical therapy for the treatment of moderate-to-severe respiratory tract
      infections is limited by their poor activity against gram-positive and atypical
      pathogens. Data from in vitro susceptibility studies and in vivo animal
      protection models suggest that the new fluoroquinolone, trovafloxacin, compared
      with ciprofloxacin and ofloxacin offers equivalent activity against gram-negative
      pathogens and improved activity against gram-positive pathogens. In particular,
      susceptibility data indicate that trovafloxacin is at least 16-fold more potent
      than either ciprofloxacin or ofloxacin against penicillin-susceptible and
      penicillin-resistant strains of Streptococcus pneumoniae. Other susceptible
      pathogens include Streptococcus pyogenes, vancomycin-susceptible Enterococcus
      faecalis and the atypical respiratory pathogens Legionella pneumophila,
      Mycoplasma pneumoniae and Chlamydia pneumoniae. In vivo studies involving models
      of protection against acute systemic infection and pneumococcal pneumonia in
      mice, and Legionnaires' disease in guinea pigs, indicate that the antibacterial
      spectrum observed for trovafloxacin in vitro extends to the in vivo setting.
      Together, these findings suggest that trovafloxacin may offer clinical efficacy
      against respiratory pathogens superior to that of ciprofloxacin and of ofloxacin,
      and may find a useful role as empiric therapy in both the community and hospital
      setting.

PMID- 9758285
TI  - A comparative study on the efficacy of the new quinolone alatrofloxacin in the
      treatment of experimental legionellosis in guinea pigs.
AB  - The in vivo efficacy of trovafloxacin, intraperitoneally administered as
      alatrofloxacin (CP-116,517), was assessed and compared with that of erythromycin,
      alone or in combination with rifampicin, in a model of Legionella pneumophila
      pneumonia in guinea pigs. Trovafloxacin (5 mg/kg administered as alatrofloxacin
      once daily for 7 days) gave a survival rate of 100% in infected animals.
      Clearance of bacteria and of bacteria-induced lesions from lungs was achieved by
      day 6 post-inoculation. The lungs of trovafloxacin-treated animals remained free
      of bacteria at day 28 post-challenge. Trovafloxacin proved as effective as
      erythromycin administered intraperitoneally, but was superior to erythromycin
      alone. or in combination with rifampicin, when given orally.

PMID- 9758286
TI  - Hepatobiliary elimination of trovafloxacin and metabolites following single oral
      doses in healthy volunteers.
AB  - Trovafloxacin, a fluoronaphthyridone derivative related to fluoroquinolones, has
      significant activity against gram-negative and gram-positive pathogens, including
      penicillin-resistant Streptococcus pneumoniae, anaerobes and atypical organisms,
      good tissue penetration and a long elimination half-life. Following oral
      administration, less than 10% of the dose is renally eliminated as unchanged
      drug. Hepatobiliary elimination of trovafloxacin was examined by comparing the
      time course and bile and serum concentrations of trovafloxacin and its
      metabolites following oral administration to three patients with in-dwelling
      nasobiliary catheters or T-tubes. Following a single 200 mg oral dose, the mean
      maximum plasma trovafloxacin concentration was 2.0+/-0.4 mg/l, the area under the
      concentration-time curve 22.0+/-5.5 mg x h/l and the elimination half-life 8.5 h.
      Values in bile for the same subjects were 27.8+/-9.6 mg/l, 327.7+/-142.9 mg x h/l
      and 10.7 h. Corresponding values for the N-acetyl metabolite in bile were 3.8+/
      3.4 mg/l, 35.3+/-29.8 mg x h/l and 8.3 h. The mean bile : serum ratio of
      trovafloxacin was 14:9 and consistent with biliary elimination. Serum
      concentrations of trovafloxacin in this study were similar to those reported in
      healthy volunteers. Bile concentrations of trovafloxacin substantially exceeded
      those of the N-acetyl metabolite, suggesting efficient clearance of the
      metabolite or that hepatic metabolism of trovafloxacin is not extensive.

PMID- 9758284
TI  - Susceptibility of European respiratory tract isolates to trovafloxacin,
      ciprofloxacin, clarithromycin, azithromycin and ampicillin.
AB  - As part of the Artemis project, 11500 isolates (3000 from patients with
      respiratory tract infections) were collected throughout six European countries
      between 1994 and 1996. Twenty-seven hospitals or laboratories participated in
      this first phase of the study. The activities of three classes of antimicrobial
      agents (fluoroquinolones, beta-lactam agents, macrolides) are presented for the
      six most frequently isolated pathogens (Streptococcus pneumoniae, Staphylococcus
      aureus, Haemophilus influenzae, Moraxella catarrhalis, Pseudomonas aeruginosa,
      Klebsiella pneumoniae). Overall, trovafloxacin and ciprofloxacin activities were
      similar for Haemophilus influenzae, Moraxella catarrhalis and Klebsiella
      pneumoniae isolates. Of the Streptococcus pneumoniae isolates, 6% were resistant
      to penicillin. Trovafloxacin had the highest activity against the Streptococcus
      pneumoniae isolates, with a minimum inhibitory concentration of 0.25 mg/l for 90%
      of isolates (MIC90); all strains tested were susceptible to trovafloxacin. The
      MIC90 of ciprofloxacin for Streptococcus pneumoniae was 3 mg/l, and overall 52%
      of the strains were susceptible; 9% were resistant. Azithromycin and
      clarithromycin exhibited similar activity against all collected pathogens, except
      Haemophilus influenzae. All strains of Haemophilus influenzae were susceptible to
      azithromycin compared with 79% for clarithromycin, with respective MIC90s of 2
      and 16 mg/l. The data presented demonstrate differences in the susceptibility
      patterns of six major respiratory tract pathogens in Europe.

PMID- 9758287
TI  - Single- and multiple-dose administration, dosing regimens, and pharmacokinetics
      of trovafloxacin and alatrofloxacin in humans.
AB  - A simplified dosing algorithm for trovafloxacin was evaluated following a single
      dose infusion of alatrofloxacin at trovafloxacin equivalent doses of 30, 100,
      200, 300 and 400 mg (57 subjects), and multiple doses of 200, 300 and 400 mg (30
      subjects). Maximum serum concentration and area under the concentration-time
      curve for trovafloxacin increased with dose. Trovafloxacin clearance (82-85 ml x
      h/kg) and volume of distribution (1.3-1.6 l/kg) were independent of dose.
      Infusion of alatrofloxacin at a trovafloxacin equivalent dose of 300 mg at 1, 2
      or 3 mg/ml over 1 h did not alter the pharmacokinetics of trovafloxacin. A plot
      of the weight-adjusted dose of trovafloxacin in individual subjects against the
      maximum serum concentration following single and multiple dosing, indicated that
      the maximum serum concentration increased 1 microg/ml for each 1 mg/kg of
      trovafloxacin administered. Thus, a prior knowledge of the desired serum
      concentration will permit appropriate dosing without the use of complex nomograms
      in patients with normal hepatic function.

PMID- 9758288
TI  - An open, controlled, crossover study on the effects of cimetidine on the steady
      state pharmacokinetics of trovafloxacin.
AB  - Twelve healthy male volunteers participated in this open, randomized, placebo
      controlled, two-way crossover study to investigate the effects of cimetidine on
      the steady-state pharmacokinetics of oral trovafloxacin. Volunteers were
      randomized to receive either 400 mg cimetidine twice daily or placebo for 5 days.
      From day 3-5, volunteers received 200 mg trovafloxacin once daily in addition to
      either cimetidine or placebo. After a minimum 7-day washout period, the study was
      repeated: those volunteers who received placebo during the first study period
      were administered cimetidine, and vice versa. The maximum observed serum
      trovafloxacin concentration, the area under the concentration-time curve of
      trovafloxacin within the dosing interval of 24 h and the earliest time to the
      maximum serum concentration for trovafloxacin in volunteers receiving concomitant
      cimetidine were 2.4 microg/ml. 27.8 microg x h/ml and 1.4 h, respectively,
      compared with 2.5 microg/ml, 27.1 microg x h/ml and 1.5 h, respectively, in
      volunteers receiving concomitant placebo. Thus. multiple dosing with cimetidine
      had no significant effect on the absorption or disposition of trovafloxacin at
      steady state. Co-administration of cimetidine and trovafloxacin was also well
      tolerated and without serious adverse effects.

PMID- 9758289
TI  - Trovafloxacin versus amoxicillin/clavulanic acid in the treatment of acute
      exacerbations of chronic obstructive bronchitis.
AB  - Treatments with once-daily trovafloxacin (200 or 100 mg) and
      amoxicillin/clavulanic acid (500/125 mg three times daily) were compared in
      adults with acute exacerbations of chronic obstructive bronchitis. At end of
      treatment, 95% (113/119) of clinically evaluable patients receiving trovafloxacin
      200 mg, 98% (113/115) of patients treated with trovafloxacin 100 mg and 97%
      (113/117) of patients receiving amoxicillin/clavulanic acid were cured or
      improved. At study end, 91%, 87% and 88%, respectively, were cured or improved.
      At end of treatment, trovafloxacin 200 mg eradicated Haemophilus influenzae in
      97% of patients, Streptococcus pneumoniae in 90% and Chlamydia pneumoniae in
      100%. The respective eradication rates for trovafloxacin 100 mg were 84%, 100%
      and 100%; those for amoxicillin/clavulanic acid were 92%, 100% and 100%. At study
      end, trovafloxacin 200 mg totally eradicated all three pathogens. Trovafloxacin
      100 mg eradicated Haemophilus influenzae in 91% of patients, Streptococcus
      pneumoniae in 100% and Chlamydia pneumoniae in 80%. Respective eradication rates
      for amoxicillin/clavulanic acid were 78%, 100% and 80%. Only 7% (10/144) of
      patients receiving trovafloxacin 200 mg reported treatment-related adverse
      events, as did 7% (10/135) of patients given trovafloxacin 100 mg and 12%
      (17/140) of patients given amoxicillin/clavulanic acid.

PMID- 9758290
TI  - Treatment of acute exacerbations of chronic bronchitis: comparison of
      trovafloxacin and amoxicillin in a multicentre, double-blind, double-dummy study.
      Trovafloxacin Bronchitis Study Group.
AB  - The efficacy and safety of trovafloxacin and amoxicillin were compared in a
      double-blind, double-dummy multicentre trial involving 412 patients (> or = 40
      years of age) with acute exacerbations of chronic bronchitis (AECBs). Patients
      were randomized to 5 days' oral treatment with 200 or 100 mg trovafloxacin
      administered once daily, or 500 mg amoxicillin given three times daily. Overall
      clinical efficacy at the end of therapy was similar in each treatment group, with
      clinical success (cure+improvement) achieved in 88% and 91% of clinically
      evaluable patients receiving trovafloxacin 200 mg and 100 mg, respectively, and
      in 89% of amoxicillin-treated patients. Corresponding rates at follow-up were
      77%, 85% and 79%, respectively. Similar responses were noted at the end of
      treatment and end of study in the intent-to-treat patients. Although all three
      treatments produced similar bacteriological efficacy, there was a trend towards
      higher eradication rates for Haemophilus influenzae among patients (both
      clinically evaluable and intent-to-treat populations) treated with trovafloxacin
      200 mg compared with those treated with amoxicillin. Both drugs were well
      tolerated, with treatment-related adverse events, of which headache and
      gastrointestinal disturbances were the most common, occurring in 12% and 6% of
      patients in the trovafloxacin 200 mg and 100 mg groups, respectively, and in 9%
      of amoxicillin-treated patients.

PMID- 9758291
TI  - Trovafloxacin versus high-dose amoxicillin (1 g three times daily) in the
      treatment of community-acquired bacterial pneumonia.
AB  - Once-daily trovafloxacin 200 mg was compared with high-dose amoxicillin, 1 g
      three times daily, given for 7 to 10 days. At end of treatment (day 10), the
      response was clinically successful (cure + improvement) in 93% of 152 clinically
      evaluable trovafloxacin patients and in 89% of 160 amoxicillin patients. At study
      end (day 35), respective rates were 91% and 81% (95% confidence interval: 1.6,
      17.6; P=0.01). In evaluable patients with positive baseline radiographs, 93% of
      trovafloxacin and 88% of amoxicillin patients demonstrated radiological
      resolution at end of treatment. Streptococcus pneumoniae and Haemophilus
      influenzae eradication rates were comparable at end of treatment in both
      treatment groups, but at study end Streptococcus pneumoniae eradication rates
      were higher in trovafloxacin patients (100% vs 81%). At study end, all four
      trovafloxacin patients with baseline penicillin-resistant Streptococcus
      pneumoniae were clinically cured with pathogen eradication, whereas two of five
      amoxicillin patients with baseline penicillin-resistant Streptococcus pneumoniae
      were clinical failures with pathogen persistence. For patients in whom no
      pathogen was identified, trovafloxacin was significantly more effective at end of
      treatment (P=0.096) and study end (P=0.013). Treatment-related adverse events
      were comparable; the most common were headache, vomiting and dizziness in
      trovafloxacin patients, and diarrhoea. headache and abdominal pain in amoxicillin
      patients.

PMID- 9758293
TI  - Acute ischaemic stroke: revascularizing therapy. Stroke Council of the American
      Heart Association.
AB  - The principal goals of thrombolytic therapy for stroke are early restitution of
      cerebral blood flow, reduction of ischaemia, and attenuation of neurological
      disability through lysis of an occluding thrombus and consequent rapid
      restoration of circulation in the affected territory. Therapy should be initiated
      as soon as possible, at least within 4-6 h of stroke onset, to prevent major
      infarction and to salvage the hypoperfused but potentially viable zone adjacent
      to the central ischaemic area known as the ischaemic penumbra. This survey
      focuses on the safety and efficacy of thrombolytic therapy in acute ischaemic
      stroke in clinical trials. The results of two successful major randomized studies
      using tissue plasminogen activator (t-PA) were recently published. Intravenous
      thrombolysis seemed to be effective in improving functional and neurological
      outcome in a clearly defined subgroup of patients meeting the inclusion criteria
      of the studies. However, the identification of those patients proved to be
      difficult and depended on expertise in recognizing the early infarction signs on
      initial computed tomography. Since treating ineligible patients is associated
      with an unacceptable risk of intracranial bleeding complications and death,
      intravenous thrombolysis should only be performed at selected centres in selected
      patients.

PMID- 9758292
TI  - Safety of trovafloxacin in treatment of lower respiratory tract infections.
AB  - Safety and toleration of oral trovafloxacin has been assessed in Phase III trials
      in patients with acute lower respiratory tract infections. Patients were treated
      orally with either trovafloxacin 100 or 200 mg (n=881) or a comparator (500 or
      1000 mg amoxicillin, or 625 mg amoxicillin/clavulanic acid; n = 593). Adverse
      events were recorded in 112 (12.7%) trovafloxacin- and 74 (12.5%) comparator
      treated patients. Frequency of effects on the autonomic nervous, musculoskeletal,
      respiratory, special senses, urinary and reproductive systems was <1%.
      Photosensitivity reactions were not reported in trovafloxacin-treated patients.
      Central or peripheral nervous system adverse effects (headache and dizziness)
      were slightly more common in trovafloxacin-treated patients (4.4% vs 1.9%).
      Patients treated with comparators experienced gastrointestinal events more
      frequently (6.1% vs 8.3%). Comparable incidences of adverse events were reported
      in patients > or = 65-years-old. Most events were mild to moderate in severity.
      Treatment was discontinued because of an adverse event in 18 (2%) trovafloxacin-
      and four (0.7%) comparator-treated patients. Despite the high prevalence of risk
      factors, serious adverse events were rare and the mortality rate over the 35-day
      study period was low: trovafloxacin 0.8%, comparator agents 1.5%. Laboratory test
      abnormalities were recorded in less than 1% of patients in either treatment
      group.

PMID- 9758294
TI  - Neuro-ophthalmology of pupillary function--practical guidelines.
AB  - An overview how to examine pupillary function and handle pupillary abnormalities
      is presented. The following issues are discussed: swinging flashlight test,
      clinical relevance of a relative afferent pupillary defect, anisocoria with
      normal light reaction, diagnosis and evaluation of Homer's syndrome, differential
      diagnosis of impaired light reaction, tonic pupil, third nerve palsy,
      supranuclear pupillary disorders, iris problems, systemic disease, measurement of
      sleepiness, and pupillography.

PMID- 9758295
TI  - Cerebrospinal fluid magnesium level as a prognostic factor in ischaemic stroke.
AB  - Magnesium has been reported to have a dilatatory effect on cerebral arteries.
      Reduction of extracellular Mg+2 has been shown to be directly correlated with the
      intensity of cerebral spasm. A neuroprotective effect of magnesium in stroke has
      also been hypothesized. The aim of our study was to examine the Mg+2 levels in
      serum and cerebrospinal fluid (CSF) in the early stage of stroke and to evaluate
      the correlation between Mg+2 levels and the development of neurological deficits.
      Between 1986 and 1994, 96 patients who had a stroke of 24- to 48-h duration were
      enrolled in the study. Serum and CSF levels of magnesium were checked on
      admission, 2448 h after the onset of stroke. Using a neurological score, the
      neurological deficit was assessed on the 1st day, 1 and 4 weeks later. Computed
      tomography (CT) was performed after 1 week, and the volume and location of
      infarction were calculated and measured. Statistical analysis was performed for
      cortical and subcortical patients separately, using Spearman correlation and
      multiple linear and logistic regression analyses. Significant correlation was
      found between CSF Mg+2 and the size of the infarct (P < 0.0001). There was no
      correlation between serum Mg+2 and CSF Mg+2 levels. Regression analysis
      demonstrated an increase in the values of the Mathew Neurological Score with
      higher CSF Mg+2 levels. This association remained true after other factors such
      as age, associated heart disease, diabetes and infarction size had been taken
      into account by the regression model. The results confirm that there is a
      relationship between a low Mg+2 concentration in CSF during the first 48 h after
      onset of ischaemic stroke and the intensity of the neurological deficit. The
      therapeutic consequence of this finding may have some importance.

PMID- 9758296
TI  - Incidence of post-lumbar puncture syndrome reduced by reinserting the stylet: a
      randomized prospective study of 600 patients.
AB  - The post-lumbar puncture syndrome (PLPS) can best be explained by prolonged
      spinal fluid leakage owing to delayed closure of a dural defect. Its incidence
      after spinal anaesthesia is much lower than after diagnostic lumbar puncture
      (LP). This difference could be caused by a strand of arachnoid, which might enter
      the needle with the outflowing cerebrospinal fluid (CSF) during diagnostic LP and
      upon removal of the needle be threaded back through the dura to produce prolonged
      CSF leakage. To find a technique that further reduces the incidence of PLPS, this
      hypothesis was tested by evaluating the effect that reinserting the stylet before
      removing the needle had on the incidence of PLPS. By reinserting the stylet to
      the tip of the needle, the hypothesized strand would be pushed out, thereby
      reducing the frequency of PLPS. Sprotte's "atraumatic needle" (21 gauge) was used
      for LP. A total of 600 patients participated in the prospective study. They were
      randomized into two groups and questioned about their complaints every day for up
      to 7 days after the LP. All LPs were performed by two experienced neurologists
      (T.B., M.S.). In 300 patients, the stylet was reinserted to the tip of the eedle;
      in the other 300 it was not reinserted. Whereas 49 of the 300 patients without
      reinsertion developed PLPS, only 15 of the 300 patients with reinsertion did.
      This significant difference (16.3 vs 5.0%, P < 0.005, chi square test) supports
      our hypothesis. On the basis of our results, we recommend reinserting the stylet
      before removing the needle in order to reduce the incidence of PLPS.

PMID- 9758297
TI  - Long-term follow-up of germinoma after stereotactic biopsy and brain
      radiotherapy: a cell kinetics study.
AB  - The primary aim of this study is to report the long-term outcome of pineal and
      suprasellar germinoma after stereotactic biopsy and whole brain radiotherapy. The
      second purpose is to report an investigation of the biological features and cell
      kinetics of this peculiar and enigmatic brain tumour. Of 34 supratentorial germ
      cell tumours diagnosed and treated between 1980 and 1993, 20 patients were found
      to be affected by true germinoma localized in the pineal and/or suprasellar
      regions. The diagnosis was achieved by stereotactic biopsy in all cases. In 14
      patients, the potential proliferative activity of the tumour was investigated by
      (3H)thymidine in vitro binding and labelling index determination. Chorionic
      gonadotropin, alpha-fetoprotein and embryonal carcinoma antigen were negative in
      the cerebrospinal fluid of these patients. All but 1 patient underwent whole
      brain radiotherapy. Clinical and neuroradiological follow-up ranged between 3 and
      13 years (mean 8). Complete clinical and neuroradiological recovery was achieved
      in all patients after treatment. Fatal recurrences owing to neuraxis
      dissemination occurred in three cases. The labelling index in the whole series
      ranged between 0.1 and 5% (median 2.5). Only syncytiotrophoblastic cells had
      proliferative activity, while none of the lymphoid-like cells showed thymidine
      labelling.

PMID- 9758298
TI  - Diagnostic value of atypical lymphocytes in cerebrospinal fluid from adults with
      enteroviral meningitis.
AB  - We have noted two morphologically distinct types of atypical lymphocytes (AL) in
      the cerebrospinal fluid (CSF) of adult patients with meningitis: one, which we
      designate type-I AL, with multilobulated nuclei resembling those of the abnormal
      cells in adult T-cell leukaemia (ATL); and another, type-II AL, characterized by
      large lymphocytes with basophilic cytoplasm and nuclei containing coarse
      chromatin. Type-I AL were detected in 25 of 39 patients (64%) with enteroviral
      and in 11 of 109 (11%) with aseptic meningitis presumed to be caused by other
      viruses, but not in meningitis resulting from Cryptococcus neofirmans (n = 14),
      Mycobacterium tuberculosis (n = 19) or acute bacterial infection (n = 49). Type-I
      AL were not seen in herpes zoster (n = 15) aseptic meningeal reactions (n = 15),
      or in leptomeningeal carcinomatosis (n = 14). Type-II AL were often present in
      meningitis of various aetiologies and in aseptic meningeal reactions, but not in
      leptomeningeal carcinomatosis. The presence of type-I AL in the CSF was found to
      be indicative of enteroviral meningitis with the highest predictive value (69%),
      while type-II AL had a lower diagnostic positive predictive value in meningitis
      of the five aetiologies above. Type-I AL immunostained for CD4, while type-II AL
      were stained for CD8. The presence of type-I AL in CSF strongly suggests
      enteroviral meningitis, which warrants careful follow-up without antifungal,
      antituberculous or antibacterial agents. However, type-I AL, which are likely to
      be virally transformed lymphocytes, must be distinguished from ATL cells, which
      frequently involve the meninges.

PMID- 9758299
TI  - Cerebral blood flow in spinocerebellar degenerations: a single photon emission
      tomography study in 28 patients.
AB  - We used single photon emission tomography to study regional cerebral perfusion in
      patients with different forms of spinocerebellar degeneration: 6 patients with
      Friedreich's ataxia (FA), 6 with early-onset cerebellar ataxia with retained
      tendon reflexes (EOCA), 5 with autosomal dominant cerebellar ataxia type 1 (ADCA
      I) and 11 with idiopathic late-onset cerebellar ataxia (ILOCA). The results were
      related to clinical and magnetic resonance imaging (MRI) findings. Cerebellar
      hypoperfusion was constant in ADCA I and frequent in patients with other
      spinocerebellar degenerations. Brain stem hypoperfusion was constant in ADCA I,
      frequent in ILOCA patients with pontocerebellar atrophy and absent in FA and
      EOCA. FA and EOCA often showed a reduction in the parietotemporal cortex blood
      flow, which was not related to cortical atrophy. ILOCA patients had an asymmetric
      pattern in the temporal areas with decreased blood flow in the right side only.
      Caudate hypoperfusion was found in ADCA I patients. Cerebral atrophy did not
      account for changes in regional blood flow, which probably indicate early
      involvement of cerebral structures.

PMID- 9758300
TI  - Quantification of post-concussion symptoms 3 months after minor head injury in
      100 consecutive patients.
AB  - Post-concussion symptoms (PCS) (such as headaches, irritability, anxiety,
      dizziness, fatigue and impaired concentration) are frequently experienced by
      patients who have sustained a minor head injury (MHI). The post-concussion
      syndrome has been defined as a clinical state where 3 or more symptoms persist
      for more than 3 months. This report focuses on the quantification of PCS
      according to the Rivermead Postconcussion Symptoms Questionnaire (RPQ). We
      studied 100 consecutive patients with MHI and normal computed tomography of the
      brain. At 3 months after injury, 62% reported the presence of one or more
      symptoms, and 40% fulfilled the diagnostic criteria for post-concussion syndrome.
      Patients with post-concussion syndrome had significantly (P < 0.001) higher RPQ
      scores (mean 19.1, SD 11.9) than those without (mean 1.2, SD 1.8). Patients on
      sick leave owing to the injury reported significantly (P = 0.05) higher RPQ
      scores (mean 10.3, SD 13.2) than those not on sick leave (mean 5.5, SD 8.6). We
      observed no association between age, gender, cause of injury, severity of injury,
      duration of amnesia and RPQ score. RPQ score provides useful information about
      the severity of PCS regardless of whether the diagnostic criteria for the post
      concussion syndrome are met or not.

PMID- 9758302
TI  - Acute pure motor neuropathy with antibodies to gangliosides in a patient with
      multiple sclerosis.

PMID- 9758301
TI  - Rapidly progressive multifocal motor neuropathy with phrenic nerve paralysis:
      effect of nocturnal assisted ventilation.

PMID- 9758303
TI  - Primary medullary haemorrhage with intractable hiccup.

PMID- 9758304
TI  - Current and future perspectives on inhaled anesthetics.
AB  - The discovery of ether anesthesia made modern surgery possible. Successive
      improvements produced today's inhaled anesthetics, compounds that allow precise
      control over the anesthetic state without compromising safety. Such control
      extends to induction and maintenance of, and recovery from, anesthesia. The
      greatest emphasis is on the last, particularly the rapid recovery obtained with
      anesthetics with low solubility in blood and tissues. The lowest solubility is
      produced by halogenation with fluoride to the exclusion of other halogens. The
      safety of anesthesia has many components. Important among these is molecular
      stability that permits elimination of the unchanged anesthetic molecule in
      expired air and provides resistance to degradation by metabolism and by carbon
      dioxide absorbents. Halogenation with fluorine produces more stable, safer
      anesthetics. Greater stability, lower solubility, and rapid recovery can decrease
      direct and indirect costs.

PMID- 9758305
TI  - Perioperative hypertension.
AB  - Increased activity or inadequate inhibition of the autonomic nervous system is
      often the cause of perioperative hypertension. The goal of treatment is to
      maintain an adequate balance between myocardial oxygen supply and demand. Newer
      agents, such as nicardipine and fenoldopam, may offer potential advantages over
      older agents. The cost:benefit ratio of therapy with these newer agents must also
      be considered. Despite the fact that perioperative hypertension is aggressively
      treated, there are no long-term, large-scale study data indicating that this
      treatment affects long-term patient outcomes.

PMID- 9758306
TI  - Levofloxacin, a second-generation fluoroquinolone.
AB  - Levofloxacin, levo-isomer of the D,L-racemate ofloxacin, is a new fluoroquinolone
      antibiotic approved for use in the United States in December 1996. It has an
      extended spectrum of activity compared with older-generation fluoroquinolones
      (ciprofloxacin, ofloxacin), with improved activity against gram-positive bacteria
      and excellent activity against gram-negative bacteria and atypical organisms.
      Although its activity against anaerobic organisms is improved over that of
      earlier fluoroquinolones, levofloxacin should not be considered a first-line
      anaerobic agent. It is available in an injectable form, as well as an oral
      formulation with virtually 100% oral bioavailability. The plasma elimination half
      life ranges from 6-8 hours in individuals with normal renal function.
      Approximately 80% of drug is eliminated unchanged in urine through glomerular
      filtration and tubular secretion. The pharmacokinetics are not appreciably
      affected by age, gender, or race when differences in renal function and body mass
      and composition are taken into account. Levofloxacin had impressive efficacy in
      clinical studies of community-acquired pneumonia, acute bacterial exacerbations
      of chronic bronchitis, acute sinusitis, skin and skin structure infections, and
      complicated urinary tract infections and pyelonephritis. It is well tolerated;
      its adverse event profile is similar to that of other fluoroquinolones, with
      gastrointestinal and central nervous system effects reported most commonly. Drug
      interactions are uncommon with levofloxacin; however, coadministration with
      antacids or with other agents containing divalent or trivalent cations reduces
      levofloxacin absorption. The agent should prove to be more effective than older
      fluoroquinolones, especially for infections caused by pneumococci highly
      resistant to penicillin.

PMID- 9758308
TI  - Effect of blood glucose concentrations on the development of chronic
      complications of diabetes mellitus.
AB  - Diabetes is associated with increased risk of cardiovascular disease, coronary
      heart disease, stroke, acute myocardial infarction, blindness, and renal failure.
      Strategies to reduce their occurrence are an essential focus of patient care.
      More than one pathogenic process is involved, and genetics influence the risk.
      Hyperglycemia is a factor in the development of microvascular and possibly
      macrovascular complications. Two possible mechanisms of glucose damage are
      glycation of proteins and the polyol pathway. Research led to the identification
      of drugs that block parts of the pathways. In clinical trials, intensive control
      of blood glucose concentrations decreased the risk of microvascular
      complications. Adverse effects associated with intensive therapy, however,
      include hypoglycemia and weight gain.

PMID- 9758307
TI  - Pharmacotherapy of primary obsessive-compulsive disorder: review of the
      literature.
AB  - Obsessive-compulsive disorder (OCD) is a chronic illness that affects 2-3% of
      Americans during their lifetime. It is characterized by recurrent obtrusive
      thoughts (obsessions) that compel patients to perform repetitive behaviors that
      can be excessively time consuming and cause marked distress. More than 40
      controlled trials have been published on the treatment of OCD. Of drugs available
      to treat the disorder, serotonin reuptake inhibitors (SRIs) are most studied.
      With SRIs, symptoms improve in 22-62% of patients, but complete remission is
      rare. An agent is often selected based on side effects and patient tolerance,
      since SRIs are all equally effective. If no response is seen with average
      dosages, dosages should be increased to the maximum within 4-8 weeks from
      starting treatment. In patients with partial response, the dosage should be
      increased to the maximum by 5-9 weeks. Before determining the effectiveness of
      therapy, a trial of 8-13 weeks is necessary.

PMID- 9758309
TI  - The role of troglitazone in treating the insulin resistance syndrome.
AB  - Insulin resistance is characterized by impaired responsiveness to endogenous or
      exogenous insulin and often results in the insulin resistance syndrome, a
      clustering of cardiovascular risk factors that includes abdominal obesity,
      hypertension, dyslipidemia, glucose intolerance, and hyperinsulinemia. Although
      the mechanism responsible for insulin resistance has not been completely defined,
      it is likely due to defective insulin receptor signaling and results in decreased
      use of glucose. Troglitazone, the first in a new class of drugs, directly
      decreases insulin resistance by improving insulin-mediated glucose disposal and
      reduces plasma insulin concentrations. Glycemic control achieved with
      troglitazone monotherapy is equivalent to that with sulfonylurea and metformin,
      and when combined with these agents offers additional plasma glucose reduction.
      Studies are necessary to determine the effect of thiazolidinediones on morbidity
      and mortality of patients with type 2 diabetes and insulin resistance.

PMID- 9758310
TI  - Monoclonal antibodies in the treatment of steroid-resistant acute graft-versus
      host disease.
AB  - Acute graft-versus-host disease (GVHD) remains the major obstacle for successful
      allogeneic bone marrow transplantation (BMT). The frequency of grade II or higher
      acute GVHD ranges from 30-50% in human leukocyte antigen (HLA)-matched sibling
      transplants and 50-80% in HLA-matched unrelated transplants. The mortality and
      morbidity associated with this complication are substantial. Corticosteroid and
      polyclonal antibodies such as antithymocyte globulin (ATG) have had little
      success in treating the disease; however, advances have been made in hybridoma
      technology and understanding its immunopathophysiology. Based on these new
      insights, monoclonal antibodies, either murine or "humanized," were tested as
      rescue treatment for acute GVHD in human trials. Complete response rates ranged
      from 20-40%, with relapse occurring often. Side effects consisted of
      constitutional symptoms such as fever, chills, hypotension, thrombocytopenia, and
      leukopenia. Limitations of monoclonal antibody treatment included low response
      rate and patient survival, high relapse rate, risk of infectious complication,
      and leukemic relapse. Future study should focus not only on improved side effects
      and efficacy of monoclonal antibodies but also on better patient survival.

PMID- 9758311
TI  - Recombinant follicle-stimulating hormone: new biotechnology for infertility.
AB  - The frequency of infertility in developed countries is approximately 8-10%. New
      drugs are available for assisted reproduction techniques. Two recombinant
      follicle-stimulating hormone (FSH) products, follitropin-beta (Follistim in the
      United States, Puregon in Europe) and follitropin-alpha (Gonal-F), join compounds
      derived through transfecting nonhuman cell lines with genetic material capable of
      replicating identical amino acid sequences to human compounds. The cell line used
      for recombinant (r)-FSH production is the Chinese hamster ovary (CHO).
      Previously, the only agents that showed benefit in controlled ovulatory
      stimulation were derived from the urine of menopausal women. Those compounds
      contain additional substances, such as urinary proteins and various amounts of
      luteininzing hormone. The amino acid sequence of r-FSH is identical to that of
      human FSH, but the two recombinant products exist in many different isoforms and
      differ from each other and from human FSH due to varied carbohydrate side chains.
      Due to variation in the carbohydrate side chains, follitropin-beta in solution
      has a higher pH than urine-derived FSH, which enhances receptor affinity and
      therefore is a greater inducer of folliculogenesis. Follitropin-beta does not
      cause endogenous production of anti-CHO or anti-FSH antibodies, and is well
      tolerated.

PMID- 9758312
TI  - Venous thromboembolism in multiple trauma patients.
AB  - Thromboembolic complications are frequent in patients with multiple trauma. The
      efficacy of unfractionated heparin for venous thrombosis prophylaxis has not been
      established. Based on limited prospective data, low-molecular-weight heparin
      appears to be more effective than unfractionated heparin and at least as
      effective as compression devices for preventing thromboembolic complications in
      these patients. Vena cava filters should be considered in high-risk patients who
      cannot receive anticoagulant therapy, but long-term filter use without
      concomitant anticoagulant therapy is associated with a substantial risk of
      recurrent thromboembolism.

PMID- 9758313
TI  - Restenosis, the Achilles' heel of coronary angioplasty.
AB  - Coronary angioplasty is widely performed for the management of symptomatic
      coronary artery disease. With improvements in technique, operator experience, and
      tools, more complex lesions are being treated. Unfortunately, luminal renarrowing
      continues to limit the long-term success of the procedure, resulting in the need
      for repeat revascularization in approximately 30% of patients within 6 months. As
      the pathophysiologic process of restenosis is better defined, various
      pharmacologic and mechanical interventions have been tried to attenuate the
      process. Some agents are antithrombotics, antiplatelets, angiotensin-converting
      enzyme inhibitors, lipid-lowering drugs, and calcium channel blockers.
      Improvement has been noted with the newer glycoprotein IIb- and IIIa-blocking
      agents, mechanical stents, and radioactive materials. Whether these new compounds
      will withstand the test of time is unknown.

PMID- 9758314
TI  - Does aspirin interfere with the therapeutic efficacy of angiotensin-converting
      enzyme inhibitors in hypertension or congestive heart failure?
AB  - We conducted a MEDLINE search of published literature from 1966 to January 1998
      regarding the impact of aspirin (ASA) on the therapeutic effect of angiotensin
      converting enzyme (ACE) inhibitors in hypertension and congestive heart failure.
      Selected references from these articles and results of recent clinical trials
      were also included. By inhibiting cyclooxygenase, ASA may interfere with the
      prostaglandin-mediated hemodynamic effects of ACE inhibitors. Although other
      nonsteroidal antiinflammatory drugs may increase blood pressure in hypertensive
      patients taking an ACE inhibitor, low-dosage (< or = 100 mg/day) ASA does not.
      However, higher dosages of ASA may attenuate the benefits of ACE inhibitors in
      patients with hypertension and/or congestive heart failure (CHF). Low-dosage ASA
      appears to interact little with ACE inhibitors, whereas higher dosages may
      produce a more significant interaction. Patients with CHF may also be more
      susceptible to this interaction because of underlying disease.

PMID- 9758315
TI  - Chest discomfort associated with liposomal amphotericin B: report of three cases
      and review of the literature.
AB  - Liposomal formulations of amphotericin B are designed to maintain therapeutic
      efficacy of amphotericin B deoxycholate while reducing its associated toxicities.
      In three patients chest discomfort occurred during planned 1-hour infusions of
      liposomal amphotericin B (AmBisome) 3 mg/kg/day during an open-label trial. The
      first patient experienced chest tightness and difficulty breathing and the second
      had dyspnea and acute hypoxia, both within 10 minutes of the start of the
      infusion. The third patient complained of chest pain 5 minutes after the start of
      two infusions. All symptoms resolved on terminating therapy. Two patients were
      later rechallenged with slower infusions and tolerated the drug well. A review of
      the English-language literature revealed only two other case reports of infusion
      related chest or pulmonary reactions with the drug, although similar reactions
      were noted in several reports of clinical trials. Further review of the
      literature revealed reports of chest and pulmonary adverse events with other
      liposomal formulations of amphotericin B, liposomal daunorubicin, liposomal
      doxorubicin, and liposomes. The pathophysiology of such reactions remains
      unclear, and premedication with diphenhydramine did not completely prevent this
      reaction in one of our patients. We recommend infusing liposomal amphotericin B
      over at least 2 hours with careful monitoring for adverse reactions.

PMID- 9758316
TI  - Alpha1-acid glycoprotein concentrations and cerebrospinal fluid drug distribution
      after subarachnoid hemorrhage.
AB  - STUDY OBJECTIVE: To test the hypothesis that changes in alpha1-acid glycoprotein
      (AAG) concentration alter central nervous system (CNS) drug distribution after
      subarachnoid hemorrhage. DESIGN: Two-phase, prospective study. SETTING:
      University-associated medical center. PATIENTS: Twenty-one patients with
      subarachnoid hemorrhage. INTERVENTION: In phase I, serum AAG concentrations of
      patients with subarachnoid hemorrhage were measured serially and compared with
      those in 21 controls undergoing elective neurosurgical procedures. In phase II,
      nimodipine was the pharmacologic probe to determine the relationship between drug
      distribution into the CNS and changes in AAG concentration. MEASUREMENTS AND MAIN
      RESULTS: Serum and cerebrospinal fluid (CSF) samples were collected from patients
      with subarachnoid hemorrhage treated with nimodipine and used to measure total
      and unbound drug concentrations. Concentrations of AAG were 39% higher in
      patients than in controls preoperatively. They decreased significantly by 24
      hours after surgery in patients and increased in controls. In both groups the
      concentrations were higher than reported normal values. During the period of
      reduced AAG concentration, calculated unbound nimodipine concentrations were 3
      fold higher (p<0.05) than at later periods, with a trend toward higher total
      concentrations. Overall, mean CSF nimodipine concentration was 6.4% of mean serum
      total concentration. The CSF concentrations decreased as AAG concentrations
      increased, independent of serum concentrations (r = -0.52, p<0.02). CONCLUSION:
      Concentrations of AAG change after subarachnoid hemorrhage and are transiently
      influenced by surgery. Unbound drug concentration increases when AAG
      concentrations decrease, whereas CSF concentrations decrease when AAG
      concentrations increase. These preliminary findings suggest that changes in AAG
      concentrations can alter unbound serum nimodipine concentrations and may affect
      CSF drug distribution.

PMID- 9758317
TI  - Comparison of bactericidal activities of intermittent and continuous infusion
      dosing of vancomycin against methicillin-resistant Staphylococcus aureus and
      Enterococcus faecalis.
AB  - STUDY OBJECTIVE: To describe the pharmacokinetic profiles of vancomycin
      administered by continuous infusion and intermittent dosing and compare the
      duration of activity of the regimens. DESIGN: Randomized, open-label, crossover
      study. SETTING: Clinical research center at an academic medical center. SUBJECTS:
      Twelve healthy, nonpregnant volunteers age 27.6 +/- 2.3 years. INTERVENTION:
      Subjects received the following intravenous vancomycin regimens: 1 g every 12
      hours; 2 g continuous infusion over 24 hours; and 1 g continuous infusion over 24
      hours. Dosages were administered with and without gentamicin 2 mg/kg.
      MEASUREMENTS AND MAIN RESULTS: Serum samples were collected, drug concentrations
      determined, and bactericidal activity measured against two isolates each of
      methicillin-resistant Staphylococcus aureus and Enterococcus faecalis. Subjects
      had poor tolerability for continuous infusions. Trough concentration for the
      intermittent regimen was 5.5 +/- 1.9 mg/ml, and steady-state concentrations were
      8.8 +/- 1.6 and 16.9 +/- 1.9 mg/ml for 1 and 2 g continuous infusions,
      respectively. In general, all regimens provided bactericidal activity throughout
      the study interval. Against one isolate of E. faecalis, 2 g continuous infusion
      plus gentamicin provided cidal activity for a significantly greater percentage of
      the dosing interval (p<0.001). CONCLUSION: Continuous infusion does not greatly
      improve the activity of vancomycin and should not be routinely administered.
      However, it may prove useful against isolates with reduced susceptibility to the
      agent.

PMID- 9758318
TI  - Evaluation of a rat model of valproate-induced obesity.
AB  - Long-term treatment with the anticonvulsant valproate (VPA) leads to well
      documented weight gain and obesity in humans. In an attempt to develop an animal
      model of this condition, adult rats were given VPA 20 g/kg (high-dose) or 2 g/kg
      (low-dose) in their daily feeding or orally 120 mg/kg body weight/day in two
      divided doses, and food intake and body weight were assessed. Valproate resulted
      in lower body weights in all protocols. Food intake was lower (p<0.001) for rats
      receiving high-dose VPA than for controls. Feed efficiency (change in weight
      divided by cumulative food intake for that period) was lower than that of
      controls for both high (p<0.0001) and low doses (NS). Metabolic rate and physical
      activity were not different between control and VPA animals, although decreased
      food intake would be expected to decrease metabolic rate. Valproate failed to
      produce obesity in rats in any treatment period. For reasons that are unclear,
      rats do not appear to be suitable as a model to study this adverse side effect of
      VPA in humans with epilepsy.

PMID- 9758319
TI  - Vancomycin pharmacokinetics in neonates receiving extracorporeal membrane
      oxygenation.
AB  - Vancomycin is administered as both prophylaxis and treatment in neonates
      receiving extracorporeal membrane oxygenation (ECMO), typically after surgery. An
      open-label, retrospective study was conducted to determine dosing strategies in
      all neonates who received vancomycin during ECMO and compare pharmacokinetic
      values with those of matched controls not receiving ECMO. Fifteen neonates
      receiving ECMO were given vancomycin infused into the circuit, with dosages based
      on weight and gestational age. Blood for serum concentrations was drawn around
      the third dose, for trough concentrations immediately before the dose, and for
      peak concentrations 1 hour after infusion. Samples were analyzed by fluorescence
      polarization immunoassay. The most frequent regimen for both groups (8 ECMO, 13
      controls) was 10 mg/kg every 8 hours. It produced peak and trough concentrations
      of 27.5 +/- 4.3 and 13.7 +/- 2.7 microg/ml, and 23.0 +/- 5.4 and 13.2 +/- 4.5
      microg/ml, respectively. Pharmacokinetic analysis using a one-compartment model
      revealed volume of distribution of 0.45 +/- 0.18 L/kg, half-life of 8.29 +/- 2.23
      hours, and total body clearance of 0.65 +/- 0.28 ml/min/kg in ECMO recipients.
      Volume of distribution and clearance were not significantly different in controls
      (0.39 +/- 0.12 L/kg, 0.79 +/- 0.41 ml/min/kg), but half-life was shorter (6.53 +/
      2.05 hrs, p = 0.02). Based on long volume of distribution in neonates receiving
      ECMO, we recommend that empiric vancomycin regimens incorporate a longer dosing
      interval than the 6-8 hours commonly recommended for term infants. The effects of
      severity of illness on drug elimination require additional study.

PMID- 9758320
TI  - Case-control study of amphotericin B in a triglyceride fat emulsion versus
      conventional amphotericin B in patients with AIDS.
AB  - We evaluated the efficacy and tolerability of amphotericin B triglyceride
      emulsion in 16 patients with acquired immunodeficiency syndrome-related candidal
      esophagitis and cryptococcosis, compared with standard amphotericin B in 24
      patients. Compared with the conventional formulation, the fat emulsion was
      administered in a significantly greater daily dose, and required shorter
      induction period and infusion time (p<0.001-<0.03). Although the two drugs had
      similar clinical and microbiologic efficacy, the fat emulsion had a better safety
      profile with respect to frequency of flu-like symptoms, other local and systemic
      adverse events, and treatment discontinuation (p<0.02-<0.05). Because it is
      easily available and inexpensive, it may have a number of advantages over the
      conventional formulation. Further similar comparisons are warranted, in addition
      to investigations to assess whether reduced toxicity can be obtained with fat
      emulsion without impairing (or possibly improving) the efficacy of this key
      antifungal agent.

PMID- 9758321
TI  - Clinical pharmacy services in hospitals educating pharmacy students.
AB  - In 1995 we conducted a national survey of 1102 acute care hospitals in the United
      States to determine types of clinical pharmacy services, patient-focused care,
      and pharmaceutical care used to educate and train pharmacy students, and compared
      outcomes with surveys in 1989 and 1992. Clinical pharmacy services offered in 50%
      or more of Pharm.D.-affiliated hospitals (core services) were drug-use
      evaluation, in-service education, pharmacokinetic consultations, adverse drug
      reaction management, drug therapy monitoring, protocol management (most common
      for aminoglycosides, nutrition, antibiotics, heparin, warfarin, theophylline),
      nutrition team, and drug counseling. Comprehensive pharmaceutical care programs
      were established in 64%, 42%, and 33% of Pharm.D., B.S., and nonteaching
      hospitals, respectively. Patient-focused care programs were beginning or
      established in 77%, 71%, and 60%, respectively. Pharmacists served as care team
      leaders in 23% of hospitals affiliated with a college of pharmacy. Most common
      ambulatory care clinics were oncology, anticoagulation, diabetes, geriatrics,
      refill, and infectious diseases/HIV. For-profit hospitals rarely provided
      education for pharmacy students. Thus patient-focused and comprehensive
      pharmaceutical care programs exist according to a hospital's academic program
      affiliation with Pharm.D. or B.S. degree program.

PMID- 9758322
TI  - Cost avoidance, acceptance, and outcomes associated with a pharmacotherapy
      consult clinic in a Veterans Affairs Medical Center.
AB  - A pharmacist-directed pharmacotherapy consult clinic (PCC) was established in an
      interdisciplinary primary care medicine continuity clinic. The pharmacist
      initiated or modified patient care plans in collaboration with primary care
      physicians and maintained care plans for 336 (32.8%) of 1023 patients enrolled in
      the continuity clinic. Clinical outcomes were positive in 88.3% of patient
      visits, with 95.7% attendance at the PCC clinic and 95% physician acceptance of
      pharmacist recommendations. Average reductions of 2.4 prescriptions/patient and
      6.9 doses/day were achieved. Actual and potential cost avoidance totaled
      $54,730.56, with actual and potential savings realized compared with dollars
      spent at a ratio of 5.8:1. The pharmacist provided value-added services and
      contributed to decreased costs associated with care.

PMID- 9758323
TI  - Frequency of hospitalization after exposure to known drug-drug interactions in a
      Medicaid population.
AB  - A matched-pair case-control analysis of Medicaid claims was performed to
      determine the risks of hospitalization associated with drug-drug interactions.
      Patients were hospitalized and controls were not. They were randomly matched
      based on contemporaneous eligibility for Medicaid benefits. Odds ratios for
      hospitalization in patients exposed to known drug-drug interactions were compared
      with those in patients exposed to one of the interacting agents. When confidence
      intervals did not overlap, the odds ratio was considered to be significantly
      increased. Odds ratios were significantly increased for many interacting drug
      pairs, and were associated with commonly recognized interactions as well as less
      widely recognized ones. Cimetidine interactions achieved significance only with
      theophylline. In the Medicaid population, exposure to a number of drug-drug
      interactions was associated with a significantly increased risk of
      hospitalization.

PMID- 9758324
TI  - Postmarketing surveillance of the safety of cyclic etidronate.
AB  - To evaluate the safety of cyclic etidronate in routine clinical practice, we
      obtained information from 550 general practices in the United Kingdom that
      provide the medical records to the General Practice Research Database. A group of
      7977 patients taking cyclic etidronate and two age-, gender-, and practice
      matched control groups, one with osteoporosis and one without, were analyzed. For
      the group taking cyclic etidronate, the average age was 71.6 years and follow-up
      was 10,328 person-years. Conditions that do not induce osteoporosis generally
      occurred in these patients at a rate comparable to that in the control groups.
      The incidence of osteomalacia was low and comparable between patients taking
      cyclic etidronate and controls with osteoporosis. No medically significant
      increases in frequency were observed among patients taking cyclic etidronate for
      a broad group of diseases that may potentially be induced by exposure to the
      drug. These data support the favorable risk:benefit ratio of cyclic etidronate.

PMID- 9758325
TI  - Seizures in patients receiving concomitant antimuscarinics and
      acetylcholinesterase inhibitor.
AB  - Seizures occurred in two patients with probable Alzheimer's disease who were
      receiving long-term treatment with metrifonate, an irreversible
      acetylcholinesterase inhibitor. In both patients seizures were associated with
      discontinuation of short-term agents with high antimuscarinic properties. Hence,
      abrupt discontinuation of antimuscarinics or anticholinergics with high
      antimuscarinic properties in patients receiving long-term acetylcholinesterase
      inhibition therapy may be associated with a reduction of seizure threshold. With
      increasing administration of acetylcholinesterase inhibitors for patients with
      Alzheimer's disease, practitioners should be aware of the potential for drug-drug
      interactions and other complications. In general, it is good medical practice to
      avoid concomitant administration with centrally acting anticholinergic agents.

PMID- 9758326
TI  - Another report of adverse reactions to immediate-release nifedipine.
AB  - Numerous case reports in the literature describe adverse drug events associated
      with immediate-release nifedipine (IRN). In addition, several publications
      alerted health care professionals regarding the agent. However, it is still
      administered, and adverse reactions are still reported. Our patient suffered IRN
      induced hypotension, myocardial ischemia, and mental status changes. We recommend
      that the use of IRN in treatment of hypertension should be either totally
      prohibited or severely restricted. The product should not be readily available
      for indiscriminate administration. Also, continuing education and training are
      required to alert all health care professionals to the serious dangers associated
      with this drug.

PMID- 9758328
TI  - Molecular characterization of a novel family of low voltage-activated, T-type,
      calcium channels.
AB  - Low voltage-activated, T-type, calcium channels are thought to be involved in
      pacemaker activity, low threshold Ca2+ spikes, neuronal oscillations and
      resonance, and rebound burst firing. Mutations in T-type channel genes may be a
      contributing factor to neurological and cardiovascular disorders, such as
      epilepsy, arrhythmia, and hypertension. Due to the lack of selective blockers,
      little is known about their structure or molecular biology. This review discusses
      our recent findings on the cloning, chromosomal localization, and functional
      expression, of two novel channels, alpha1G and alpha1H. The biophysical
      properties of these cloned channels (distinctive voltage dependence, kinetics,
      and single channel conductance) demonstrates that these channels are members of
      the T-type Ca2+ channel family.

PMID- 9758327
TI  - Overview of voltage-dependent calcium channels.
AB  - Voltage-dependent calcium channels couple electrical signals to cellular
      responses in excitable cells. Calcium channels are crucial for excitation
      secretion coupling in neurons and endocrine cells, and excitation-contraction
      coupling in muscle. Several pharmacologically and kinetically distinct calcium
      channel types have been identified at the electrophysiological and molecular
      levels. This review summarizes the basic properties of voltage-dependent calcium
      channels, including mechanisms of ion permeation and block, gating kinetics, and
      modulation by G proteins and second messengers.

PMID- 9758329
TI  - Molecular basis of drug interaction with L-type Ca2+ channels.
AB  - Different types of voltage-gated Ca2+ channels exist in the plasma membrane of
      electrically excitable cells. By controlling depolarization-induced Ca2+ entry
      into cells they serve important physiological functions, such as excitation
      contraction coupling, neurotransmitter and hormone secretion, and neuronal
      plasticity. Their function is fine-tuned by a variety of modulators, such as
      enzymes and G-proteins. Block of so-called L-type Ca2+ channels by drugs is
      exploited as a therapeutic principle to treat cardiovascular disorders, such as
      hypertension. More recently, block of so-called non-L-type Ca2+ channels was
      found to exert therapeutic effects in the treatment of severe pain and ischemic
      stroke. As the subunits of different Ca2+ channel types have been cloned, the
      modulatory sites for enzymes, G-proteins, and drugs can now be determined using
      molecular engineering and heterologous expression. Here we summarize recent work
      that has allowed us to determine the sites of action of L-type Ca2+ channel
      modulators. Together with previous biochemical, electrophysiological, and drug
      binding data these results provide exciting insight into the molecular
      pharmacology of this voltage-gated Ca2+ channel family.

PMID- 9758330
TI  - Physical link and functional coupling of presynaptic calcium channels and the
      synaptic vesicle docking/fusion machinery.
AB  - N- and P/Q-type calcium channels are localized in high density in presynaptic
      nerve terminals and are crucial elements in neuronal excitation-secretion
      coupling. In addition to mediating Ca2+ entry to initiate transmitter release,
      they are thought to interact directly with proteins of the synaptic vesicle
      docking/fusion machinery. As outlined in the preceding article, these calcium
      channels can be purified from brain as a complex with SNARE proteins which are
      involved in exocytosis. In addition, N-type and P/Q-type calcium channels are co
      localized with syntaxin in high-density clusters in nerve terminals. Here we
      review the role of the synaptic protein interaction (synprint) sites in the
      intracellular loop II-III (L(II-III)) of both alpha1B and alpha1A subunits of N
      type and P/Q-type calcium channels, which bind to syntaxin, SNAP-25, and
      synaptotagmin. Calcium has a biphasic effect on the interactions of N-type
      calcium channels with SNARE complexes, stimulating optimal binding in the range
      of 10-20 microM. PKC or CaM KII phosphorylation of the N-type synprint peptide
      inhibits interactions with native brain SNARE complexes containing syntaxin and
      SNAP-25. Introduction of the synprint peptides into presynaptic superior cervical
      ganglion neurons reversibly inhibits EPSPs from synchronous transmitter release
      by 42%. At physiological Ca2+ concentrations, synprint peptides cause an
      approximate 25% reduction in transmitter release of injected frog neuromuscular
      junction in cultures, consistent with detachment of 70% of the docked vesicles
      from calcium channels based on a theoretical model. Together, these studies
      suggest that presynaptic calcium channels not only provide the calcium signal
      required by the exocytotic machinery, but also contain structural elements that
      are integral to vesicle docking, priming, and fusion processes.

PMID- 9758331
TI  - Interactions between presynaptic calcium channels and proteins implicated in
      synaptic vesicle trafficking and exocytosis.
AB  - Monoclonal antibodies were generated by immunizing mice with chick brain synaptic
      membranes and screening for immunoprecipitation of solubilized omega conotoxin
      GVIA receptors (N-type calcium channels). Antibodies against two synaptic
      proteins (p35--syntaxin 1 and p58--synaptotagmin) were produced and used to
      purify and characterize a ternary complex containing N-type channels associated
      with these two proteins. These results provided the first evidence for a specific
      interaction between presynaptic calcium channels and SNARE proteins involved in
      synaptic vesicle docking and calcium-dependent exocytosis. Immunoprecipitation
      experiments supported the conclusion that syntaxin 1/SNAP-25/VAMP/synaptotagmin I
      or II complexes associate with N-type, P/Q-type, but not L-type calcium channels
      from rat brain nerve terminals. Immunofluorescent confocal microscopy at the frog
      neuromuscular junction was consistent with the co-localization of syntaxin 1,
      SNAP-25, and calcium channels, all of which are predominantly expressed at active
      zones of the presynaptic plasma membrane facing post-synaptic folds rich in
      acetylcholine receptors. The interaction of proteins implicated in calcium
      dependent exocytosis with presynaptic calcium channels may locate the sensor(s)
      that trigger vesicle fusion within a microdomain of calcium entry.

PMID- 9758333
TI  - Post-translational modifications of beta subunits of voltage-dependent calcium
      channels.
AB  - Different post-translational modifications of Ca channel beta subunits have been
      identified. Recent studies have characterized the palmitoylation of the Ca
      channel beta2a subunit, as well as one effect of this modification on channel
      function. The potential importance of palmitoylation on other channel properties
      is discussed. Other studies have addressed the role of phosphorylation of beta
      subunits in the regulation of voltage-dependent Ca channels. Phosphorylation of
      beta subunits by second messenger-activated protein kinases, as well as by
      unidentified protein kinases, may affect interactions between channel subunits
      and other aspects of channel function. The differential modification of Ca
      channel beta subunit isoforms by post-translational events likely results in
      diversely regulated channels with unique properties.

PMID- 9758332
TI  - Structures and functions of calcium channel beta subunits.
AB  - Calcium channel beta subunits have profound effects on how alpha1 subunits
      perform. In this article we summarize our present knowledge of the primary
      structures of beta subunits as deduced from cDNAs and illustrate their different
      properties. Upon co-expression with alpha1 subunits, the effects of beta subunits
      vary somewhat between L-type and non-L-type channels mostly because the two types
      of channels have different responses to voltage which are affected by beta
      subunits, such as long-lasting prepulse facilitation of alpha1C (absent in
      alpha1E) and inhibition by G protein betagamma dimer of alpha1E, absent in
      alpha1C. One beta subunit, a brain beta2a splice variant that is palmitoylated,
      has several effects not seen with any of the others, and these are due to
      palmitoylation. We also illustrate the finding that functional expression of
      alpha1 in oocytes requires a beta subunit even if the final channel shows no
      evidence for its presence. We propose two structural models for Ca2+ channels to
      account for "alpha1 alone" channels seen in cells with limited beta subunit
      expression. In one model, beta dissociates from the mature alpha1 after proper
      folding and membrane insertion. Regulated channels seen upon co-expression of
      high levels of beta would then have subunit composition alpha1beta. In the other
      model, the "chaperoning" beta remains associated with the mature channel and
      "alpha1 alone" channels would in fact be alpha1beta channels. Upon co-expression
      of high levels of beta the regulated channels would have composition
      [alpha1beta]beta.

PMID- 9758334
TI  - Genetic analysis of voltage-dependent calcium channels.
AB  - Molecular cloning of calcium channel subunit genes has identified an unexpectedly
      large number of genes and splicing variants, and a central problem of calcium
      channel biology is to now understand the functional significance of this genetic
      complexity. While electrophyisological, pharmacological, and molecular cloning
      techniques are providing one level of understanding, a complete understanding
      will require many additional kinds of studies, including genetic studies done in
      intact animals. In this regard, an intriguing variety of episodic diseases have
      recently been identified that result from defects in calcium channel genes. A
      study of these diseases illustrates the kind of insights into calcium channel
      function that can be expected from this method of inquiry.

PMID- 9758335
TI  - Metabolism and trafficking of N-type voltage-operated calcium channels in
      neurosecretory cells.
AB  - The N-type voltage-operated calcium channel has been characterized over the years
      as a high-threshold channel, with variable inactivation kinetics, and a unique
      ability to bind with high affinity and specificity omega-conotoxin GVIA and
      related toxins. This channel is particularly expressed in some neurons and
      endocrine cells, where it participates in several calcium-dependent processes,
      including secretion. Omega-conotoxin GVIA was instrumental not only for the
      biophysical and pharmacological characterization of N-type channels but also for
      the development of in vitro assays for studying N-type VOCC subcellular
      localization, biosynthesis, turnover, as well as short-and long-term regulation
      of its expression. We here summarize our studies on N-type VOCC expression in
      neurosecretory cells, with a major emphasis on recent data demonstrating the
      presence of N-type channels in intracellular secretory organelles and their
      recruitment to the cell surface during regulated exocytosis.

PMID- 9758337
TI  - Allogeneic transplantation of selected CD34+ cells from peripheral blood:
      experience of 62 cases using immunoadsorption or immunomagnetic technique.
      Spanish Group of Allo-PBT.
AB  - The objective of this study was to analyze CD34+ cell recovery and T cell
      depletion (TCD) achieved in CD34+ cell grafts using either immunoadsorption or
      immunomagnetic methods applied to leukapheresis products from healthy donors. We
      also wanted to determine the kinetics of engraftment and incidence and severity
      of graft-versus-host disease (GVHD) after allogeneic transplantation of selected
      CD34+ cells. HLA-identical sibling donors received G-CSF. After leukapheresis,
      peripheral blood progenitor cells were selected using immunoadsorption (Ceprate
      SC) (n = 38) or immunomagnetic (Isolex 300) (n = 24) methods. Sixty-two patients,
      with a median age of 42 years (range 17-60) diagnosed with hematological
      malignancies were conditioned with either cyclophosphamide and total body
      irradiation (n = 43) or busulphan and cyclophosphamide (n = 19). GVHD prophylaxis
      consisted of cyclosporin A (CsA) and prednisone (n = 48), CsA alone (n = 11) and
      CsA and methotrexate (n = 3). The median yield and purity of CD34+ cells after
      the procedure was 65 and 66% with immunoadsorption, and 48 and 86% with
      immunomagnetic method, respectively. The median number (range) of CD34+ cells
      infused into the patients was 3.5 x 10(6)/kg (1-9.6). The median number (range)
      of CD3+ cells administered was 0.4 x 10(6)/kg (0.01-2) using immunoadsorption and
      0.14 x 10(6)/kg (0.03-2.5) using immunomagnetic methods. Neutrophil recovery >500
      and >1000/microl was achieved at a median (range) of 13 days (8-22) and 14 days
      (9-31), respectively. Platelets recovered to >20000 and >50000/microl at a median
      (range) of 13 days (0-128) and 18 days (0-180), respectively. Two patients
      developed graft failure. Acute GVHD in patients at risk was clinical grade 0 (n =
      43), I (n = 8), II (n = 4) and III (n = 1). No patient developed acute GVHD grade
      IV. Chronic GVHD was limited in two cases and extensive in four cases. The
      actuarial probability of acute GVHD II-IV was 10% (95% CI, 1-19%), and of
      extensive chronic GVHD was 12% (95% CI, 11-13%). The cumulative incidence of
      transplant-related mortality was 12.6%, and this figure was 9% at 6 months. In
      conclusion, with the immunomagnetic procedure, a lower recovery and higher purity
      of CD34+ cells, and stronger TCD is obtained as compared to immunoadsorption (P =
      0.008, P < 0.0001 and P = 0.0002, respectively). Our results also indicate that
      allogeneic transplantation of selected CD34+ cells is associated with a very
      rapid engraftment and with a low incidence of severe GVHD.

PMID- 9758336
TI  - Differential expression and association of calcium channel subunits in
      development and disease.
AB  - Voltage-gated calcium channels (VDCC) are essential to neuronal maturation and
      differentiation. It is believed that important signaling information is encoded
      by VDCC-mediated calcium influx that has both spatial and temporal components.
      VDCC are multimeric complexes comprised of a pore-forming alpha1 subunit and
      auxiliary beta and alpha2/delta subunits. Changes in the fractional contribution
      of distinct calcium conductances to the total calcium current have been noted in
      developing and differentiating neurons. These changes are anticipated to reflect
      the differential expression and localization of the pore-forming alpha1 subunits.
      However, as in vitro studies have established that beta regulates the channel
      properties and targeting of alpha1, attention has been directed toward the
      developmental expression and assembly of beta isoforms. Recently, changes in the
      beta component of the omega-conotoxin GVIA (CTX)-sensitive N-type VDCC have
      indicated differential assembly of alpha1B with beta in postnatal rat brain. In
      addition, unique properties of beta4 have been noted with respect to its temporal
      pattern of expression and incorporation into N-type VDCC complexes. Therefore,
      the expression and assembly of specific alpha1/beta complexes may reflect an
      elaborate cellular strategy for regulating VDCC diversity. The importance of
      these developmental findings is bolstered by a recent study which identified
      mutations in the beta4 as the molecular defect in the mutant epileptic mouse
      (lethargic; lh/lh). As beta4 is normally expressed in both forebrain and
      cerebellum, one may consider the impact of the loss of beta4 upon VDCC assembly
      and activity. The importance of the beta1b and beta4 isoforms to calcium channel
      maturation and assembly is discussed.

PMID- 9758339
TI  - Phase II study of high-dose thiotepa and hematopoietic stem cell transplantation
      in children with solid tumors.
AB  - From 1987 to 1995, 22 children with refractory solid tumors entered a phase II
      study of high-dose thiotepa (HDT) (900 mg/m2) followed by stem cell
      transplantation (SCT) in the Pediatrics Department of the Institut Gustave
      Roussy. Tumor types were rhabdomyosarcoma (eight), osteosarcoma (seven),
      neuroblastoma (three), Ewing's sarcoma (three) and Burkitt's lymphoma (one).
      Before HDT, all had been extensively treated with conventional chemotherapy,
      surgical resection of the primary tumor (13/22) and of metastases (6/22), and
      radiotherapy of the primary tumor in three patients. All had measurable disease,
      at the site of the primary tumor (3 patients), of the metastases (9 patients) or
      both (10 patients). Toxicity from the HDT was severe but acceptable. No toxicity
      related death occurred. The median duration of neutropenia and thrombocytopenia
      was 18 days (5-37) and 30 days (7-377), respectively. Septicemia was documented
      in four patients. Severe diarrhea was observed in seven patients. Mild hepatic
      toxicity occurred 18 times. No CR and 11/22 PR were documented: osteosarcoma 4/7,
      rhabdomyosarcoma 4/8, Ewing's sarcoma 2/3; 1/1 Burkitt's lymphoma progressed. We
      conclude that at a dose of 900 mg/m2 followed by SCT support in these heavily
      pretreated children, the main toxicity induced by thiotepa was digestive. The
      response rate observed, especially in sarcoma, is particularly encouraging.
      Thiotepa should be further evaluated in HDC regimens either in combination with
      other alkylating agents or in rapidly cycled courses of HDC with SCT.

PMID- 9758338
TI  - A high resolution HLA class I and class II matching method for bone marrow donor
      selection.
AB  - HLA matching in bone marrow transplantation has an important role in determining
      successful outcome. However HLA typing of both potential related and unrelated
      donors can be both time-consuming and laborious, and does not always resolve
      accurately the true level of histocompatibility. We have utilised a method,
      reference strand mediated conformation analysis (RSCA), which is technically
      simple and allows high resolution matching for all HLA loci, for the typing of 48
      patients and their potential 120 donors. The results indicate that RSCA can
      detect many mismatches that are not routinely identified by conventional HLA
      typing methods. In addition, RSCA can be applied for the simultaneous analysis of
      multiple potential BM donor samples in order to quickly identify the best match
      for each patient.

PMID- 9758340
TI  - Low incidence of acute graft-versus-host disease and recurrent leukaemia in
      patients undergoing allogeneic haemopoietic stem cell transplantation from
      sibling donors with methotrexate and dose-monitored cyclosporin A prophylaxis.
AB  - One of the major aims of allogeneic haemopoietic stem cell transplantation has
      been the effective suppression of graft-versus-host disease (GVHD) without loss
      of a graft-versus-leukaemia effect. For GVHD suppression, one of the most
      frequently used regimens has been the combination of cyclosporin (CsA) and a
      short course of methotrexate (MTX) although the optimal usage of these agents
      remains unclear. Here, we report the results of 55 patients with standard risk
      leukaemia who have undergone allogeneic transplantation using either bone marrow
      (n = 48) or G-CSF mobilised peripheral blood stem cells (n = 7) using CsA and MTX
      for GVHD prophylaxis where the dosage of CsA was regularly adjusted to maintain a
      trough whole blood level of 95-205 ng/ml for the first 50 days post-transplant.
      To achieve this level of CsA in the immediate post-transplant period, over 40% of
      patients required dose adjustments of CsA as a result of sub-therapeutic levels
      on day +1 post-transplant. The achievement of CsA levels within the therapeutic
      range was expedited following the introduction of a sliding scale for dose
      adjustment. With this regimen we have observed a low incidence of acute GVHD with
      only 11% of patients developing > or =grade II disease. With a median follow-up
      of 66 months (range 8-132) the probability of relapse is only 6.6%. The disease
      free survival probability for all patients was 72% at 5 years. These results
      demonstrate that effective GVHD prevention with CsA and MTX can be achieved
      without a high risk of recurrent leukaemia provided that rapid attainment of
      therapeutic CsA levels is achieved and maintenance within a low therapeutic range
      may help to maximise this effect.

PMID- 9758341
TI  - Variables associated with the platelet count 6 weeks after autologous peripheral
      blood progenitor cell transplantation.
AB  - While abundant data exist documenting variables associated with early platelet
      engraftment after autologous PBPC transplantation, data concerning later
      sustained platelet engraftment is sparse. We retrospectively examined a series of
      80 patients undergoing autologous PBPC transplantation with respect to their
      platelet count 6 weeks after transplant. Underlying diagnoses included breast
      cancer (n = 33), non-Hodgkin's lymphoma (n = 32), Hodgkin's disease (n = 9), and
      other hematologic malignancies (n = 6). Patients received G-CSF for PBPC
      mobilization and collected a target threshold number of 2.0 x 10(6) CD34+ cells
      per kilogram. A univariate analysis revealed that a diagnosis of breast cancer,
      fewer courses of prior chemotherapy, younger age and complete remission were
      associated with a higher 6-week platelet count. Additionally, the ability to
      collect the threshold number of CD34+ with fewer sessions of leukapheresis was
      also associated with a higher 6-week platelet count. The platelet count and the
      white blood cell count at the initiation of PBPC collection was also associated
      with a higher 6-week platelet count. A multivariate analysis revealed a higher
      platelet count on the first day of pheresis, fewer phereses required to collect 2
      x 10(6) CD34+ cells per kilogram, and a diagnosis of breast cancer were all
      associated with a higher 6-week post-transplant platelet count. Seven patients
      failed to reach a 6-week platelet count of 30 x 10(9)/l and an additional five
      patients had a platelet count of 30-50 x 10(9)/l. We conclude that underlying
      clinical characteristics, as well as hematologic variables at the time of PBPC
      collection, influence later, sustained platelet engraftment. A percentage of
      patients have poor sustained platelet engraftment and may be candidates for new
      cytokines that specifically target megakaryocyte growth and development.

PMID- 9758343
TI  - Bone marrow transplantation in children: consequences for renal function shortly
      after and 1 year post-BMT.
AB  - The aim of this study was to investigate the effect of a bone marrow
      transplantation (BMT) on renal function in children. In a 5-year period, 142
      children received a BMT at the Department of Pediatrics of the University
      Hospital Leiden. The study was performed retrospectively using the estimated
      glomerular filtration rate before and 1 year after BMT, and weekly measurements
      of serum creatinine during the first 3 months after BMT for assessment of renal
      function. Patient characteristics (sex, age, diagnosis), conditioning regimen,
      type of BMT, major complications (sepsis, veno-occlusive disease and graft-versus
      host disease (GVHD)) and the use of nephrotoxic medication were listed. In the
      first 3 months after BMT 17 (12%) patients died, 13 from transplant-related
      complications other than renal failure and four from relapse of the disease.
      Forty-eight children (34%) had a period with acute renal insufficiency. A high
      pre-BMT serum creatinine, transplantation with either a non-HLA-identical related
      or a matched unrelated donor were risk factors for acute renal insufficiency
      after BMT. Sepsis and the use of intravenous vancomycin were risk factors for
      acute renal insufficiency only for patients with a high pre-BMT serum creatinine.
      GVHD seemed to have a beneficial effect on renal function of BMT recipients. One
      year after BMT a total of 35 (25%) patients had died, 16 from transplant-related
      complications and 19 from relapse of the disease; another 17 patients could not
      be evaluated. Twenty-five of 90 evaluable children (28%) had chronic renal
      insufficiency. Chronic renal insufficiency 1 year after BMT was correlated with a
      high serum creatinine in the first 3 months after BMT. None of the children of
      this retrospective study on renal function after BMT needed dialysis.

PMID- 9758342
TI  - Use of the polymerase chain reaction and direct sequencing analysis to detect
      cells with the t(14;18) in autologous bone marrow from patients with follicular
      lymphoma, before and after in vitro treatment.
AB  - Between August 1993 and February 1994, 25 patients with follicular or transformed
      follicular lymphoma had bone marrow harvested at St Bartholomew's Hospital (SBH)
      with a view to proceeding to high-dose treatment comprising: cyclophosphamide 60
      mg/kg x 2 and total body irradiation, 200 cGy x 6, supported by autologous bone
      marrow transplantation (ABMT). The marrow mononuclear cell fraction was treated
      in vitro with four anti-B cell antibodies and baby rabbit complement. The aim of
      this study was to determine whether in vitro treatment of the marrow could remove
      morphologically undetectable lymphoma cells. PCR analysis for the t(14;18) was
      used to determine the presence or absence of lymphoma. At the time of the bone
      marrow harvest, 21/25 bone marrow samples were positive for the t(14;18), in
      15/22 patients, the rearrangement could also be demonstrated in peripheral blood.
      After in vitro treatment, 18/21 samples (86%) remained 'PCR positive'. Sequence
      analysis of the t(14;18) PCR products was performed on the latter and on lymph
      node biopsy material taken at diagnosis from 12 patients. The same t(14;18)
      sequences were found in the bone marrow harvest samples as in the patients'
      original biopsies. These results suggest that this form of in vitro treatment
      does not completely eradicate the t(14;18) bearing clone. New and better methods
      need to be developed.

PMID- 9758344
TI  - Avascular necrosis of bone following allogeneic stem cell transplantation: MR
      screening and therapeutic options.
AB  - With improvement in long-term survival after allogeneic stem cell
      transplantation, late complications with significant morbidity are of increasing
      importance. We retrospectively analysed 272 recipients of an allogeneic stem cell
      transplant for the development of osteonecrosis. The incidence among allograft
      recipients was 6.3% (17/272) for the whole patient population, and 11.8% (17/144)
      for long-term survivors. All patients were treated with high-dose prednisolone,
      16 for severe acute or extensive chronic graft-versus-host disease (GVHD) and one
      patient for graft rejection. The mean age at time of diagnosis was 33 years
      (range 16-45) and the mean time from transplant to diagnosis of osteonecrosis was
      13 months. Osteonecrosis was diagnosed by magnetic resonance (MR) imaging, which
      allows early detection of osteonecrosis and assessment of stage. At the time of
      diagnosis, eight patients had stage I, three patients stage II, three patients
      stage III and three patients stage IV osteonecrosis according to MR criteria. All
      but one patient had involvement of the femoral head. The median total dosage of
      prednisolone at the time of diagnosis was 189 mg/kg (single manifestation 150
      mg/kg; multiple manifestations 313 mg/kg) with a total range of 13-555 mg/kg. Six
      patients were treated by conservative means, 77 patients underwent surgery (three
      core decompression, eight joint replacement). MR screening of patients receiving
      high-dose steroids might help to detect osteonecrosis at an early stage and thus
      prevent progression by early intervention, for example, by core decompression.

PMID- 9758345
TI  - Ultrasound-guided fine needle cutting biopsy for the characterization of diffuse
      liver diseases in bone marrow transplant patients.
AB  - Liver disease is a frequent complication in bone marrow transplant recipients and
      may occur early or late in the post-transplant period. Using ultrasound-guided
      fine needle (1.2 mm, 18 G) cutting biopsy, we studied six patients with undefined
      late post-BMT liver disease. No procedure-related complications occurred and all
      liver biopsies were informative, leading to changes in therapeutic approach. In
      our small series, the most frequent cause of hepatic damage was drug toxicity. US
      guided fine needle cutting biopsy is a useful and easy tool for the work-up of
      unexplained post-BMT liver disease.

PMID- 9758346
TI  - Transfusion support using filtered unscreened blood products for cytomegalovirus
      negative allogeneic marrow transplant recipients.
AB  - It has been suggested that leukoreduced unscreened blood products can be used as
      an alternative to components from cytomegalovirus (CMV)-seronegative donors in
      order to prevent transmission of CMV from transfusions for CMV-seronegative
      marrow transplant recipients with CMV-seronegative donors, but confirmatory data
      are lacking. A retrospective chart review was undertaken for patients undergoing
      allogeneic transplantation over a 4-year period during which blood products were
      filtered for CMV-seronegative patients with CMV-seronegative donors when CMV
      seronegative components were not available. Forty-five CMV-seronegative patient
      donor pairs were identified. Only one patient developed CMV disease (pneumonia)
      and no other patients developed an infection. In this group of patients, the rate
      of CMV infection was 2.7% (95% CI, 0-8%) by life-table analysis. We conclude that
      filtered unscreened blood products as partial transfusion support for CMV
      seronegative marrow transplant recipients were associated with a low incidence of
      CMV infection, justifying further evaluation of filtered blood products as total
      transfusion support for this patient population. However, since CMV infections
      still occur, continued surveillance by periodic culture or other techniques is
      warranted.

PMID- 9758348
TI  - Hyperbaric oxygen in the treatment of refractory haemorrhagic cystitis.
AB  - Haemorrhagic cystitis is a common and often debilitating complication of
      chemotherapy for which treatment is frequently unsatisfactory. With over 80 cases
      reported of radiation-induced cystitis treated successfully with hyperbaric
      oxygen, attention is now turning to the treatment of chemotherapeutic agent
      induced cystitis. We report a case of haemorrhagic cystitis occurring after
      autologous peripheral blood stem cell transplantation for multiple myeloma. The
      patient had received cyclophosphamide and busulfan and had BK and adenoviruria.
      The haemorrhage was refractory to multiple conventional treatments but resolved
      after a course of hyperbaric oxygen.

PMID- 9758347
TI  - Treatment of relapse after allogeneic bone marrow transplantation with
      unmanipulated G-CSF-mobilized peripheral blood stem cell preparation.
AB  - Donor lymphocyte infusions (DLI) are an effective treatment of leukemia relapse
      after allogeneic bone marrow transplantation. Undesired side-effects are the
      development of graft-versus-host disease (GVHD) and the occurrence of
      pancytopenia in some patients. In a pilot study, we investigated if unmanipulated
      G-CSF-mobilized peripheral blood stem cells which naturally contain large numbers
      of T lymphocytes (D-PBSC/LI) would be equally effective or even superior than DLI
      in generating a graft-versus-leukemia reaction (GVL) but could mitigate or
      prevent the development of pancytopenia. We treated 12 patients with CML chronic
      phase (n = 5), CML blast crisis (n = 2), AML (n = 2), ALL (n = 1), CLL (n = 1)
      and multiple myeloma (n = 1). In five patients with acute leukemia or CML blast
      crisis D-PBSC/LI followed intensive chemotherapy (group A), in seven patients D
      PBSC/LI were given without any prior chemotherapy (group B). In group A two
      patients were evaluable for hematologic toxicity. Leukopenia <1000/microl lasted
      for 10 and 19 days, and thrombocytopenia <20,000/microl for 11 and 13 days,
      respectively. In group B leukopenia <1000/microl and thrombocytopenia
      <20,000/microl was observed in only one patient. Moderate cytopenia developed in
      four of five evaluable patients. A complete remission could be achieved in all
      seven patients with CML who all developed acute and/or chronic GVHD. None of the
      remaining five patients achieved a complete remission despite acute and/or
      chronic GVHD in two of them. Four patients died from disease progression, one
      patient from a secondary lymphoma, and one patient as a result of uncontrolled
      GVHD. In conclusion, D-PBSC/LI is effective in inducing GVL reaction but it does
      not prevent pancytopenia in each case. It remains unclear if it mitigates the
      incidence and severity of pancytopenia.

PMID- 9758349
TI  - Acyclovir-resistant herpes simplex virus infections in a bone marrow transplant
      population.
AB  - Over a 3-month period, four patients who had received unrelated donor (UD) bone
      marrow transplants (BMT) presented with severe mucocutaneous herpes simplex virus
      (HSV) infection while receiving acyclovir (ACV) prophylaxis. Sensitivity testing
      of the isolates revealed three to be acyclovir-resistant and in one patient the
      infection was also characterised by a marked failure to respond to foscarnet
      (phosphonoformic acid). The emergence of ACV-resistant HSV infections in
      themselves is a new and challenging problem, and yet a far greater problem will
      become evident if these infections develop resistance to non thymidine kinase
      dependent therapy.

PMID- 9758350
TI  - Total body irradiation and cyclophosphamide is a conditioning regimen for
      unrelated bone marrow transplantation in a patient with chronic myelogenous
      leukemia and renal failure on hemodialysis.
AB  - Five years after the diagnosis of Ph chromosome-positive chronic myeloid leukemia
      (CML) a 31-year-old patient developed malignant nephrosclerosis with renal
      failure. He then underwent an allogeneic unrelated BMT in first chronic phase
      CML. The preparative regimen consisted of fractionated total body irradiation
      (TBI) and cyclophosphamide (CY). We studied the pharmacokinetics of
      cyclophosphamide on hemodialysis and compared clinical parameters including time
      to engraftment and toxicity with parameters of a patient with normal renal
      function who also received an unrelated marrow as treatment for CML in first
      chronic phase. Our results suggest that TBI/CY is a suitable conditioning regimen
      for allogeneic transplantation in patients with hematological malignancy and
      renal failure on hemodialysis.

PMID- 9758351
TI  - Relapsed chronic myeloid leukemia in accelerated phase 10 years after allogeneic
      bone marrow transplantation: full chimera reconversion with donor peripheral
      blood stem cells infusion.
AB  - We report the case of a 44-year-old male who relapsed in accelerated phase
      chronic myeloid leukemia 10 years after a successful bone marrow transplantation
      from his HLA-identical brother, and 3 years after 12 months treatment with
      interferon-alpha (IFN-alpha) for chronic active hepatitis C (CAH). The patient
      was infused with G-CSF-primed peripheral blood cells (PBSC) from the original
      bone marrow donor and a full donor reconstitution, with no detectable molecular
      disease, was obtained within 4 months without clinical aplasia or GVHD, nor help
      from other forms of chemotherapy or use of biological response modifiers. We
      speculate that IFN-alpha for CAH delayed the onset of a clinical recurrence of
      chronic myeloid leukemia and that in advanced disease PBSCs can provide an
      advantageous alternative to donor lymphocyte infusion (DLI).

PMID- 9758352
TI  - Autologous reconstitution with BCR-ABL-negative haematopoiesis after T cell
      depleted allogeneic BMT for CML.
AB  - We report a patient with Ph chromosome-positive CML who underwent an HLA
      identical T cell-depleted BMT from a sibling donor. DNA polymorphism analysis
      showed complete donor chimaerism after BMT, followed by mixed chimaerism of
      granulocytes, natural killer cells and B lymphocytes, with T lymphocytes host
      derived at day +120 post BMT. From month +20 haematopoiesis was exclusively of
      host origin in all cell lineages. RT-PCR was used in order to detect residual
      disease, but at the time, analysis did not show BCR-ABL transcripts. This case is
      unusual in that non-malignant stem cells of recipient origin survived the
      transplant and reconstituted haematopoiesis after BMT. Two years post transplant,
      no molecular or haematological relapse was documented. The observation that
      subsequent recipient recovery without molecular relapse implies that, at least in
      this case, the GVL effect can occur in the absence of donor T cells.

PMID- 9758353
TI  - Matched unrelated allogeneic bone marrow transplantation for recurrent malignant
      lymphoma in a patient with X-linked lymphoproliferative disease (XLP).
AB  - A 14-year-old male and a maternally related cousin were diagnosed with X-linked
      lymphoproliferative disease (XLP) after developing recurrent B-NHL, characterized
      by long disease-free intervals and absence of an increased chemoresistance of the
      recurrent lymphomas. The demonstration of different clonal IgH gene
      rearrangements in two of the lymphomas from one of the patients further supports
      that the lymphomas were clonally unrelated. The cousin underwent matched related
      BMT, whereas the proband received a deliberately delayed MUD BMT in third CR.
      Both are in CR 68 months and 21 months, respectively, post-BMT. Delaying BMT
      probably contributes to reducing treatment-related morbidity. We suggest MUD BMT
      as a feasible curative strategy for XLP patients with B-NHL lacking matched
      related donors.

PMID- 9758354
TI  - CD34+-enriched donor lymphocyte infusions in a case of pure red cell aplasia and
      late graft failure after major ABO-incompatible bone marrow transplantation.
AB  - A variety of immunohematological complications may occur after ABO-incompatible
      BMT. We report a CML patient (blood group O) who received a BMT from an HLA
      identical sibling (blood group AB). The transplant was followed by normal myeloid
      and megakaryocytic engraftment, but erythroblastopenia persisted for more than
      200 days after BMT. By bone marrow culture studies, a complement-dependent serum
      inhibitor of hemopoiesis was detected, suggesting immunological inhibition of
      erythropoiesis. The patient was resistant to a number of treatments such as
      intravenous gamma-globulins, prednisolone and high-dose erythropoietin. Full
      engraftment with normal blood counts and marrow cellularity was achieved after
      two dose-escalating CD34+-enriched donor lymphocyte infusions (DLI). This
      experience suggests that CD34+-enriched DLI may be an effective treatment for
      patients with delayed engraftment or late graft failure due to major ABO
      incompatibility.

PMID- 9758355
TI  - Donor lymphocyte infusion at unstable mixed chimerism in an allogeneic BMT
      recipient for chronic granulomatous disease.
AB  - We report a 14-year-old boy who had successfully received allogeneic BMT for
      chronic granulomatous disease and 3 years later was treated with donor lymphocyte
      infusion (DLI, 3.3 x 10(8) cells/kg) at unstable mixed chimerism in association
      with reduced neutrophil function. Following DLI, the patient developed transient
      acute hepatic GVHD, which was confirmed by liver biopsy and was manageable with
      cyclosporin A and prednisolone. The patient eventually attained complete
      chimerism with improved neutrophil function. At the time of writing (2.5 years
      from the DLI), the patient is doing well, free from infectious episodes and
      chronic GVHD. Our experience suggests that DLI could be a safe and effective
      strategy for dissolution of unstable mixed chimerism in BMT recipients for
      inherited disorders.

PMID- 9758356
TI  - PBPC as an alternative cell therapy for post-transplant relapse in CML.

PMID- 9758357
TI  - How should corticosteroids be used in the treatment of acute GVHD? EBMT Chronic
      Leukemia Working Party. European Group for Blood and Marrow Transplantation.

PMID- 9758358
TI  - Inoculation of a portion of marrow for transplant as a way to accelerate marrow
      recovery.

PMID- 9758359
TI  - Expression of beta-catenin, alpha-catenin, and E-cadherin in Barrett's esophagus
      and esophageal adenocarcinomas.
AB  - Loss of expression and function of the E-cadherin/catenin membrane complex can
      result in loss of cell adhesion and contribute to invasive or metastatic
      potential in carcinomas. The aim of this study was to examine the expression of
      alpha- and beta-catenin and E-cadherin in Barrett's esophagus with and without
      dysplasia and in esophageal adenocarcinomas and to identify any relationship with
      tumor growth pattern and clinical outcome. Immunoperoxidase staining for alpha-
      and beta-catenin and E-cadherin was performed on specimens of Barrett's esophagus
      with and without dysplasia and on 54 esophageal adenocarcinoma specimens.
      Membranous staining for all of the components was seen in normal gastric and
      esophageal mucosa. Abnormal expression of beta-catenin, alpha-catenin, and E
      cadherin was significantly associated with higher degrees of dysplasia in
      Barrett's esophagus. Fourteen of 16 cases of high grade dysplasia and 7 of 7
      cases of intramucosal carcinoma showed abnormal expression of beta-catenin,
      compared with 3 of 6 cases indefinite for dysplasia and 11 of 17 cases with low
      grade dysplasia (P = 0.022). Similar results were seen for expression of alpha
      catenin (P < .01) and E-cadherin (P = .049). In esophageal adenocarcinomas,
      preserved expression of these proteins occurred more frequently in well
      differentiated tumors; abnormal expression was more common in diffusely
      infiltrative poorly differentiated tumors that did not form glands. Focal nuclear
      staining for beta-catenin was present in two high-grade dysplasias, two
      intramucosal carcinomas, and five adenocarcinomas. No survival advantage was
      demonstrated for patients whose tumors retained expression of these cell adhesion
      components. In conclusion, abnormal expression of the E-cadherin/catenin membrane
      complex is common in esophageal adenocarcinoma and occurs early in the
      dysplasia/carcinoma sequence in Barrett's esophagus, indicating that disturbances
      in this cell adhesion complex might be important in tumorigenesis and tumor
      progression in this disorder.

PMID- 9758360
TI  - Pleomorphic lobular carcinoma of the breast: clinicopathologic features of 12
      cases.
AB  - Pleomorphic lobular carcinoma (PLC) of the breast was recently identified as a
      histologic variant of infiltrating lobular carcinoma (ILC) with a poor prognosis.
      Twelve cases identified from a large series of breast carcinomas were studied
      retrospectively. Of 11 cases with adequate follow up, 9 were fatal. This was
      significantly worse than either infiltrating ductal carcinoma (IDC) or classical
      ILC (P < or = .002), even when stratified by axillary lymph node status. Among
      the fatal cases, the median survival time was 2.1 years, significantly shorter
      than that for classical lobular, but not ductal, carcinoma A distinctive pattern
      of in situ carcinoma, which has been described as PLC in situ, was identified in
      7 of the 12 patients. This in situ component was composed of tumor cells with
      nuclear atypia, cytologically similar to the invasive tumor. Most PLCs lacked
      estrogen and progesterone receptors and stained with BRST-2, an antibody to gross
      cystic disease fluid protein-15, suggesting the presence of apocrine
      differentiation. In summary, PLC has many of the histologic features of ILC but
      has anaplastic nuclei, abundant cytoplasm, and apocrine differentiation. PLC is
      often aneuploid, usually lacks steroid receptors, and has a significantly poorer
      prognosis than does classical ILC.

PMID- 9758361
TI  - p53 and c-erbB-2 as markers of resistance to adjuvant chemotherapy in breast
      cancer.
AB  - Recent literature suggests that c-erbB-2 and p53 alteration might be linked to
      drug resistance. This study investigates the relation of c-erbB-2 oncoprotein
      overexpression and p53 protein accumulation with prognosis in patients with node
      positive breast cancer (NPBC) and assesses the modifying effect of these markers
      on response to short (1-10 courses) or prolonged (> 10 courses) adjuvant
      chemotherapy. This study is based on 458 patients with NPBC diagnosed from 1980
      to 1986, with an average of 10 years of follow-up. Marker expression was
      evaluated by immunohistochemical analysis on formalin-fixed, paraffin-embedded
      material with antibodies to c-erbB-2 and p53. c-erbB-2 was expressed in 17.2% of
      the cases, and 19.1% of the tumors stained positively for p53. By multivariate
      analysis, women with prolonged adjuvant chemotherapy had better survival than
      those with a short course of chemotherapy among patients whose tumor lacked c
      erbB-2 oncoprotein expression (P = .0245) or p53 protein accumulation (P =
      .0477). Prolonged chemotherapy, however, was associated with little or no change
      in survival among patients whose tumor expressed those markers. The present study
      adds support to the hypothesis linking c-erbB-2 and p53 expression to drug
      resistance.

PMID- 9758362
TI  - Laparoscopic biopsy for suspected abdominal lymphoma.
AB  - This study retrospectively reviewed the findings in laparoscopic biopsy specimens
      from 51 consecutive patients with suspected abdominal lymphoproliferative
      disorders. Histologic evaluation was supplemented (as necessary) by paraffin
      section or frozen-section immunohistochemical analysis or by Southern blot
      hybridization. The laparoscopic procedure was diagnostic of a lymphoproliferative
      disorder in 24 patients (47%), of other neoplasms in 5 patients (10%), and of
      reactive tissue in 11 patients (22%); no tissue could be obtained for technical
      reasons (adhesions and inaccessible lesions) in 11 patients (22%). The 24
      patients with lymphoproliferative disorders diagnosed by laparoscopic techniques
      included 14 patients with a new diagnosis of lymphoma and 10 patients with
      recurrent disease; pathologic findings were diagnostic of diffuse large cell
      lymphoma (11 patients), follicular lymphoma (11 patients), chronic lymphocytic
      leukemia (1 patient), and lymphocyte-predominant Hodgkin's disease (1 patient).
      Previous abdominal cytologic or core-needle biopsy specimens from 11 lymphoma
      patients did not yield an unequivocal diagnosis or subtype of lymphoma. The 11
      patients (22%) in whom laparoscopic techniques did not produce a tissue sample
      needed laparotomy (10 patients) or femoral lymph node biopsy (1 patient) to
      document the diagnosis of large cell lymphoma (2 patients), follicular lymphoma
      (5 patients), composite lymphoma (1 patient), myeloma (1 patient), neurofibroma
      (1 patient), and reactive lymph nodes (1 patient). In the majority of patients
      with suspected abdominal lymphoma, laparoscopic techniques provide sufficient
      tissue for the diagnosis and classification of lymphoma and for the diagnosis of
      other causes of abdominal lymphadenopathy.

PMID- 9758363
TI  - Performance of liquid-based, thin-layer cervical cytology: correlation with
      reference diagnoses and human papillomavirus testing.
AB  - The performance of thin-layer cervical cytology with the use of ThinPrep (Cytyc
      Corporation, Boxborough, MA) was assessed by comparing the original independent
      diagnosis of ThinPrep slides and conventional smears prepared from 1780 split
      samples with the most abnormal diagnosis per patient on the basis of an
      independent pathologist's masked review and with the detection of cancer
      associated types of human papillomavirus (HPV) DNA. Cases were selected on the
      basis of the original diagnoses to include all discordant pairs (those diagnosed
      as atypical squamous cells of undetermined significance or higher grade, n =
      1017), all concordant abnormal pairs (n = 444), and a random 5% of concordant
      normal pairs (n = 319). In screening centers, thin-layer cytology detected 135
      (70.3%) of 192 women diagnosed as having squamous epithelial lesions or a higher
      grade in the independent review, whereas locally read smears detected 91 (47.4%)
      of these patients (P < .001). In hospital-based cytology laboratories, thin-layer
      cytology detected 308 (86.3%) of 357 women diagnosed with SILs or a higher grade
      in the independent review, compared with 283 (79.3%) diagnosed with smears (P =
      .011). Cancer-associated types of HPV DNA were detected in a slightly higher
      proportion of women with smears diagnosed as SILs than in women with thin-layer
      cytology diagnosed as SILs, whereas the overall number of HPV-associated SILs
      diagnosed was higher with thin-layer cytology. These data suggest that the
      ThinPrep method detects a higher percentage of SILs as defined in a masked,
      independent review than do concurrently prepared smears and that diagnoses of
      SILs rendered with ThinPrep correlate with the detection of cancer-associated
      types of HPV.

PMID- 9758364
TI  - Clinicopathologic comparison of vulvar and extragenital lichen sclerosus:
      histologic variants, evolving lesions, and etiology of 141 cases.
AB  - Lichen sclerosus (LS) is a persistent inflammatory dermatosis of unknown etiology
      with a predilection for the vulva, where it is a risk factor for carcinoma. We
      performed a clinicopathologic study on 121 cases of vulvar LS and 20 of
      extragenital LS, and we reviewed 49 vulvectomy specimens with LS to define
      morphologic findings, identify the earliest lesions, and correlate outcomes with
      histologic findings. The vulvar LS lesions were pruritic/burning, white/red, ill
      defined patches predominately affecting the labia, perineum, introitus, and
      perianal region. The extragenital LS lesions were asymptomatic, pink to ivory
      white, coalescing macules or patches with well-defined borders. All of the LS
      cases showed dermal sclerosis, vacuolar interface changes, and a lymphocytic
      infiltrate underlying the sclerosis, but vulvar LS showed changes of lichen
      simplex chronicus or spongiotic dermatitis, dermal eosinophils, and a frequent
      absence of atrophy. The presence of eosinophilic spongiosis, marked lymphocyte
      exocytosis, dermal eosinophils, and excoriations predicted poor symptomatic
      response to treatment. Patch testing is recommended for these individuals as
      these findings suggest an allergic contact dermatitis. Examination of vulvectomy
      specimens revealed either a lichenoid interface or a spongiotic dermatitis in
      continuity with pathognomonic LS. Additionally, in these contiguous regions, we
      identified histologic changes that might represent evolving lesions of LS,
      suggesting a multifactorial etiology. In conclusion, vulvar LS was significantly
      different clinicopathologically from extragenital LS, and if only classic
      features of LS were used for pathologic diagnosis, many cases of vulvar LS would
      be missed. Therefore, we proposed as the minimal histologic criterion for LS the
      presence of a vacuolar interface reaction pattern in conjunction with dermal
      sclerosis (homogenized and hyalinized eosinophilic collagen bundles) of any
      thickness intervening between the inflammatory infiltrate and epithelium and or
      vessel walls.

PMID- 9758366
TI  - Frequency of bcl-2 expression in non-Hodgkin's lymphoma: a study of 778 cases
      with comparison of marginal zone lymphoma and monocytoid B-cell hyperplasia.
AB  - The oncoprotein, bcl-2, is expressed in various types of non-Hodgkin's lymphoma
      (NHL). Immunodetection of this protein is a useful method for distinguishing
      follicular hyperplasia from follicular lymphoma. Although bcl-2 might also be a
      useful marker for distinguishing reactive monocytoid B-cell hyperplasia from its
      putative malignant counterpart, marginal zone lymphoma, there were no extensive
      studies to date that tested this. Therefore, we performed a survey of bcl-2
      expression in 778 cases of NHL using immunohistochemical techniques applied to
      routinely processed and paraffin-embedded tissues. Of 20 reactive monocytoid B
      cell hyperplasias, none were bcl-2 positive, compared with 118 (79%) of 150
      marginal zone lymphomas (P = .001). With respect to the follicular lymphomas in
      our study, of the 110 Grade I lymphomas, 107 (97%) were bcl-2 positive, 119 (83%)
      of the 143 Grade II lymphomas were positive, and 71 (74%) of the 96 Grade III
      lymphomas were positive. The bcl-2 positivity of Burkitt-like high-grade B-cell
      lymphoma was significantly different from that of Burkitt's lymphoma (4 [67%] of
      6 vs. 0 of 5; P = .02). T-cell NHL had a significantly lower bcl-2 positivity
      than did B-cell NHL (10 [45%] of 22 vs. 627 [83%] of 756; P = .0001). Therefore,
      bcl-2 is a highly sensitive marker for follicular lymphoma and a useful marker
      for distinguishing reactive monocytoid B-cell hyperplasia from marginal zone
      lymphoma The significant difference in bcl-2 positivity between Burkitt-like high
      grade B-cell lymphoma and Burkitt's lymphoma suggests an additional diagnostic
      use for this protein.

PMID- 9758367
TI  - Prognostic factors in gastric cancer.
AB  - Molecular assays related to cell proliferation correlate with stage and/or
      survival in a variety of tumors. We immunostained formalin-fixed, paraffin
      embedded tissue sections from 61 patients with gastric adenocarcinoma (21 biopsy
      and 40 gastrectomy specimens) for cyclin A, cyclin B1, p34cdc2, p120, MIB1, and
      proliferating cell nuclear antigen (PCNA) by automated methods. HER-2/neu gene
      amplification was analyzed by automated fluorescence in situ hybridization
      (FISH). Immununostains, FISH results, and pathologic stage were compared with
      length of survival. Forty-three percent of the cases showed amplification of HER
      2/neu. Sixty-two percent of cases showed positive immunostaining for cyclin A,
      38% for cyclin B1, 31% for p34cdc2, 49% for p120, 69% for MIB1, and 33% for PCNA.
      On univariate analysis, pathologic stage (P = .003) and HER-2/neu gene
      amplification (P < .001) correlated with length of survival. Cyclin A, cyclin B1,
      p34cdc2, p120, MIB1, and PCNA did not correlate with survival. On multivariate
      analysis, pathologic stage (P = .015) and HER-2/neu gene amplification (P = .002)
      independently predicted survival. These correlations were unrelated to tubular or
      signet ring cell histologic characteristics or to location within the cardia or
      more distally. Pathologic stage and HER-2/neu gene amplification by FISH were
      independent prognostic factors in gastric cancer, but the various proliferation
      markers that we studied did not correlate with survival.

PMID- 9758365
TI  - Seprase, a membrane-bound protease, is overexpressed by invasive ductal carcinoma
      cells of human breast cancers.
AB  - The increased cell surface expression of the serine integral membrane protease,
      seprase, has been associated with the invasive behavior of human melanoma cell
      lines in vitro. The present study investigates the expression of seprase in
      malignant, premalignant, benign, and normal human breast tissues. The 170-kDa
      gelatinase activity of seprase was identified in extracts of infiltrating ductal
      carcinomas (IDC). Protein bands corresponding to the proteolytically active 170
      kDa seprase dimer and its 97-kDa seprase subunit protein were identified by
      immunoblot analysis of IDC extracts using an antiserum elicited against
      immunoaffinity-purified seprase. Immunohistochemical analysis of seprase
      expression in 41 formalin-fixed and paraffin-embedded specimens of human breast
      tissue revealed preferential immunoreactivity with the malignant cells of IDC (27
      cases). Within individual IDC specimens, the stromal cells or morphologically
      normal epithelium revealed low labeling that was always significantly less than
      the labeling of neoplastic cells. Lymph node metastases of IDC cells were also
      strongly positive, but the lymphoid tissue in affected nodes was not stained.
      Neoplastic cells in DC in situ (5 cases) exhibited variable levels of staining.
      Epithelial cells of benign fibroadenoma specimens (2 cases) and benign
      proliferative breast disease (5 cases) exhibited little or no immunoreactivity.
      Epithelial cells of normal breast tissue (1 case) were not stained. The
      overexpression of seprase by DC cells is consistent with seprase having a role in
      facilitating invasion and metastasis of IDC of the breast. The cell surface
      localization of seprase could be used to target therapeutic agents to malignant
      breast cells.

PMID- 9758368
TI  - Expression of MMP-1, TIMP-1, and type I collagen in laryngeal carcinoma.
AB  - Matrix metalloproteinases (MMPs) are thought to play an important role in tumor
      invasion and metastasis. To our knowledge, however, no previous report examined
      the histologic localization of matrix metalloproteinase-1 (MMP-1), tissue
      inhibitor of metalloproteinase-1 (TIMP-1) and Type I collagen in laryngeal
      carcinoma from the same samples. In this study, immunohistochemical staining for
      MMP-1, TIMP-1, and Type I collagen was performed on paraffin-embedded sections
      from 83 laryngeal squamous cell carcinomas. Twenty of the 83 tumors were examined
      for MMP-1 and TIMP-1 mRNA using in situ hybridization (ISH). Immunohistochemical
      and ISH analyses indicated that squamous cancer cells as well as stromal cells
      such as fibroblasts, macrophages, and mononuclear and endothelial cells expressed
      MMP-1 and TIMP-1 in the area adjacent to the tumor. The localization of MMP-1 and
      TIMP-1 protein is similar to that of their respective transcripts. Dense or
      moderate patterns of Type I collagen were associated with a tendency toward
      positivity for TIMP-1 and negativity for MMP-1 (P < .002). A sparse pattern of
      Type I collagen was associated with a tendency toward positivity for MMP-1 and
      negativity for TIMP-1 (P < .004). The patterns of Type I collagen staining
      correlated significantly with imbalances in MMP-1 and TIMP-1 expression (P <
      .001). Matrix degradation and remodeling in squamous cell carcinoma of the larynx
      might be attributable to an imbalance in the expression of MMP-1 and TIMP-1.

PMID- 9758369
TI  - Overexpression of the ERK/MAP kinases in oral squamous cell carcinoma.
AB  - Mitogen-activated protein kinase (MAPK) is a serine-threonine kinase that is
      activated by various extracellular stimuli. Extracellular signal-regulated
      kinases (ERK1 and ERK2), an MAPK subfamily, are activated by many oncogenes, such
      as ras and raf, and they induce cell proliferation. myc is also an oncogene and
      one of the targets of ERKs. Mutations of ras and overexpression of myc were found
      in various human cancers, and ERKs were also reported to play a role in
      carcinogenesis. In this study, we examined 39 biopsy specimens of oral squamous
      cell carcinoma (OSCC) and 5 of normal gingival mucosa for the expression of ERK
      protein and the proliferation marker, MIB-1 (Ki-67 antibody). Thirteen OSCC
      specimens and five normal gingival biopsies were also examined for the expression
      of ERKs mRNA by in situ hybridization. Double staining for ERKs and MIB-1 was
      also performed. Histologically, 18 patients (46%) were diagnosed with well
      differentiated SCC, 17 (44%) with moderately differentiated SCC, and 4 (10%) with
      poorly differentiated SCC. The histologic grade correlated with the MIB-1 index.
      The localization of ERK1 was similar to that of ERK2. Positive signals for ERK
      proteins were localized in superficial keratinocytes in normal gingival mucosa,
      whereas these mRNAs were weakly positive in the basal and spinous layer. Basal
      and suprabasal cells were positive for MIB-1. In well-differentiated and
      moderately differentiated OSCC, positive signals for ERK mRNA and proteins were
      found at higher levels than in normal gingival mucosa in keratotic cells around
      cancer pearls. Some cells showed positive signals for ERKs and MIB-1.
      Furthermore, most cancer cells in poorly differentiated SCC were positive for
      both ERK and MIB-1. The histologic grade was statistically related to the
      percentage of cells positive for both ERK and MIB-1. This suggested that ERKs
      might be related to proliferation in OSCC.

PMID- 9758370
TI  - Expression of bcl-2, p53, and p21 in benign and malignant prostatic tissue before
      and after radiation therapy.
AB  - Abnormalities in genes of the apoptotic pathway might contribute to survival in
      prostatic cancer (PCa) cells after radiation therapy (RT). We investigated the
      immunohistochemical expression of the products of the p53, p21WAF1, and bcl-2
      genes in pre-RT and post-RT biopsy specimens from 38 patients with locally
      advanced PCa. All of the 38 patients underwent a uniform protocol of RT with or
      without neoadjuvant hormonal therapy. Immunohistochemical staining for expression
      of the products of the p53, p21WAF1, and bcl-2 genes was performed on material
      from pre-RT and post-RT specimens. Sufficient tissue for analysis was available
      from 25 of the pre-RT and 38 of the post-RT biopsy specimens. In benign prostatic
      epithelium, RT resulted in expression of p53 (2 [8%] of 25 pre-RT specimens vs.
      15 [71%] of 21 post-RT specimens; P < .001) and increased expression of bcl-2 (1
      [5%] of 18 pre-RT vs. 18 [86%] of 21 post-RT; P < .001). There was no change in
      the expression of p21WAF1 (1 [4.5%] of 22 pre-RT vs. 4 [17%] of 23 post-RT; P =
      NS). Post-RT specimens were positive for PCa in 24 (63%) of 38 cases. In the PCa
      tissue, p53 expression was seen in 10 (42%) of 24 pre-RT and 12 (63%) of 19 post
      RT samples (P = NS). A significant upregulation of p53 was seen in the subgroup
      of patients who did not receive neoadjuvant hormonal therapy (9 [82%] of 11 vs. 3
      [38%] of 8; P = .05). No significant change in p21WAF1 (5 [21%] of 24 vs. 5 [33%]
      of 15; P = NS), or bcl-2 (4 [18%] of 22 vs. 3 [21%] of 14; P = NS) expression was
      detected. There was no significant correlation between immunohistochemical
      expression of apoptosis-related markers and treatment failure. We concluded that
      RT induced upregulation of the bcl-2 and p53 gene products in benign prostatic
      tissue and that this likely reflected a protective mechanism in genetically
      unaltered epithelium. Increased p53 expression in PCa was only seen in patients
      without neoadjuvant hormonal treatment, indicating that the cancer cells with
      abnormal p53 were at least partially protected from RT-induced cell death.

PMID- 9758371
TI  - Sarcoid, amyloid, and acute myocardial failure.
AB  - We report the case of a 58-year-old woman, with an 8-year history of pulmonary
      sarcoidosis, who died in acute myocardial failure after cardiac catheterization.
      Systemic amyloid, likely of the AL type, was found to involve her myocardial
      interstitium and intramyocardial coronary arteries, as well as her spleen,
      thyroid, kidneys, and bone marrow. Her acute myocardial failure was thought to be
      the result of focal myocardial infarcts secondary to amyloid vasculopathy and of
      superimposed chronic restrictive myocardial function caused by amyloid. Five
      previously reported cases of concurrent sarcoidosis and AA-type amyloid remind us
      that there is significant experimental data implicating the inflammatory process
      of sarcoidosis in the causation of AA-type amyloidosis. The concurrence of
      sarcoidosis and AL-type systemic amyloid seen in this patient was reported in the
      literature once before, and we think the concurrence was a coincidence.

PMID- 9758372
TI  - Splenic marginal zone cell lymphoma associated with clonal B-cell populations
      showing different immunoglobulin heavy chain sequences.
AB  - Splenic marginal zone cell lymphomas (SMZCLs) are low-grade B-cell lymphomas that
      usually present with massive splenomegaly and subtle (subleukemic) peripheral
      blood involvement. Polymerase chain reaction (PCR) analysis of peripheral blood
      from a patient with subleukemic SMZCL showed evidence of two clonal
      immunoglobulin heavy chain (IgH) gene rearrangements. IgH PCR analysis of DNA
      derived from the patient's splenic neoplasm demonstrated a single clonal IgH
      rearrangement, which had a different electrophoretic mobility from either of the
      two PCR products detected in the patient's peripheral blood. Additional
      characterization of these PCR products by DNA sequencing demonstrated two
      independent IgH rearrangements in the peripheral blood, one of which used IgH
      joining region 6c (JH6C) and the other JH4. A different IgH rearrangement was
      present in the splenic tumor, which used JH4a. No sequences from the splenic
      neoplasm were detected in the peripheral blood and vice versa. This case
      illustrates that PCR might reveal monoclonal populations in peripheral blood
      unrelated to the presence of lymphoma in other anatomic compartments.

PMID- 9758374
TI  - An easy and quick stain for the demonstration of Helicobacter pylori.

PMID- 9758375
TI  - Regional left ventricular wall motion abnormalities in myocardial infarction and
      mitral annular descent velocities studied with pulsed tissue Doppler imaging.
AB  - We evaluated global left ventricular (LV) systolic function from mitral annular
      systolic motion velocities measured by pulsed tissue Doppler imaging in patients
      with previous myocardial infarction (MI) and LV regional wall motion
      abnormalities. The subject group consisted of 45 patients with wall asynergies, 3
      with ischemic cardiomyopathy, 8 with dilated cardiomyopathy, and 15 healthy
      control subjects. The peak systolic descent velocity (Sw) and the time from the
      electrocardiographic Q wave to the peak of the systolic wave (Q-Sw) were measured
      at 6 mitral annular sites obtained from 2-dimensional apical long-axis, 4
      chamber, and 2-chamber echocardiograms; these variables were compared with the LV
      ejection fraction (EF) calculated from the left ventriculogram. The mean Sw at
      the sites corresponding to the infarct regions was significantly lower and the
      mean Q-Sw was significantly longer in the MI groups than in the control group.
      The mean Sw and Q-Sw at all 6 sites in the ischemic and dilated cardiomyopathy
      groups were significantly lower and longer, respectively, than those of the
      control group. There were significant correlations between the EF and the means
      of the Sw and Q-Sw values at the sites corresponding to the infarct regions in
      the MI groups. In the ischemic and dilated cardiomyopathy groups, significant
      correlations existed between the EF and the means of the Sw and Q-Sw values at
      all 6 sites. Thus the parameters obtained from mitral annular systolic motion
      velocities with pulsed tissue Doppler imaging reflect LV asynergy corresponding
      to the infarct regions in patients with MI, and global LV systolic function may
      be evaluated with these parameters.

PMID- 9758377
TI  - Left ventricular contraction pattern changes with age in normal adults.
AB  - Left ventricular ejection fraction is known to be unchanged or slightly increased
      with advancing age. This echocardiographic study, including 40 healthy subjects
      18 to 70 years old, shows that this is a net effect of decreased contractions in
      the long axis and increased in the short axis. From age 18 to 70 years, the
      longitudinal shortening decreases by 20% (P < .001) and the short-axis diameter
      shortening increases by 18% (P=.012). Multiple regression analysis showed strong
      correlation to age for both short- and long-axis contractions and no significant
      additional explicatory power when the variables systolic blood pressure, left
      ventricular wall thickness, heart rate, or sex were included. There was no
      significant correlation between diameter changes during the isovolumic phases and
      age. The findings have practical implications when calculating ejection fraction
      from M-mode measurements. Teichholz's formula will overestimate ejection fraction
      in elderly subjects, and calculation of ejection fraction from mitral ring motion
      will overestimate it in young subjects.

PMID- 9758376
TI  - Nongeometric quantitative assessment of right and left ventricular function:
      myocardial performance index in normal children and patients with Ebstein
      anomaly.
AB  - Assessment of ventricular systolic function has been based on the geometric
      models of ventricular shape. This study was designed to define normal values for
      a nongeometric myocardial performance index (MPI) in children and to evaluate the
      utility of MPI in congenital heart disease. The MPI measures the ratio of total
      time spent in isovolumic activity (isovolumic contraction time and isovolumic
      relaxation time) to the ejection time. The right ventricular (RV) and left
      ventricular (LV) MPI were measured in 152 normal children (ages 3 to 18 years)
      and 45 preoperative patients with Ebstein anomaly (age 1 week to 52 years). In
      normal children, the RV MPI was 0.32+/-0.03 and the LV MPI was 0.35+/-0.03. In
      the Ebstein group, both RV and LV MPI were abnormally increased compared with age
      matched normal subjects (Ebstein group: RV MPI=0.49+/-0.12, LV MPI=0.42+/-0.09, P
      < .001). Increasing RV dysfunction was associated with progressively increasing
      (abnormal) values of RV MPI (P < .001). The myocardial performance index
      quantitatively reflects ventricular performance in patients with complex
      ventricular geometry (ie, Ebstein anomaly). In the absence of a geometric
      solution, this nongeometric index is particularly appealing for the assessment of
      RV or LV performance.

PMID- 9758378
TI  - Right ventricular volumes revisited: a simple model and simple formula for
      echocardiographic determination.
AB  - Our objective was to establish a crescentic model of the right ventricle as the
      basis of a reported 2/3 (Area)(Length) empirical formula for volume. This formula
      has been investigated by others without cognizance of its connection to a clear
      geometric model. The particular model, an ellipsoidal shell or difference of
      ellipsoids, has been investigated by several groups by using different volume
      formulas. Accordingly, we obtained echocardiographic images in 2 orthogonal
      planes from 7 patients and 4 volunteers. Specified area and length measurements
      from these images were used to calculate right ventricular volumes. These volumes
      were compared with values determined through multislice, magnetic resonance
      imaging with summation of lumen areas, a widely accepted standard. Obtained high
      correlations compared favorably with those of previous investigators who used
      equivalent but less well understood methods. We conclude that the ellipsoidal
      shell model of the right ventricle provides a simple area-length formula for the
      determination of lumen volume with echocardiography.

PMID- 9758380
TI  - Comparison of transesophageal Doppler methods with angiography for evaluation of
      the severity of mitral regurgitation.
AB  - Doppler evaluation of mitral regurgitation remains difficult; thus, a head-to
      head comparison of the diagnostic accuracy of Doppler methods was undertaken.
      Fifty patients with native mitral regurgitation underwent multiplane
      transesophageal echocardiography within 5 days of catheterization. Angiographic
      grade of mitral regurgitation and, in 20 patients with grade II-IV regurgitation,
      invasively determined regurgitant stroke volume were compared with color Doppler
      area, regurgitant jet diameter, ratio of systolic to diastolic peak pulmonary
      venous flow velocities, and (based on the proximal convergence zone) maximal
      regurgitant flow rate and regurgitant orifice area. Rank correlation coefficients
      of angiographic grade with Doppler parameters were 0.61 for color jet area, -0.61
      for pulmonary venous flow velocity ratio, 0.69 for color jet diameter, 0.79 for
      maximal regurgitant flow rate, and 0.78 for regurgitant orifice area (all P <
      .01). Convergence zone-based parameters also correlated best (r=0.73) with
      invasively determined regurgitant stroke volume. Receiver operating
      characteristic curve analysis confirmed higher diagnostic accuracy for proximal
      jet width and proximal convergence zone parameters than for color jet area or
      pulmonary venous flow velocity ratio. Proximal convergence zone parameters and
      proximal color jet diameter best distinguished severe from mild forms of mitral
      regurgitation.

PMID- 9758379
TI  - Quantification of aortic regurgitant volume by a newly developed automated
      cardiac flow measurement method: an in vitro study.
AB  - BACKGROUND: Quantifying regurgitant volumes is important for treatment of
      patients with valvular aortic regurgitation. Simple, reliable methods to quantify
      aortic regurgitation have been sought both in the catheterization laboratory and
      the echocardiography laboratory. OBJECTIVES: The aim of our study was to
      investigate the applicability of a new automated cardiac flow measurement method
      with color Doppler velocity data for quantifying retrograde flow volumes of
      aortic regurgitation in an ascending aorta model. METHODS AND RESULTS: A 2
      chamber pulsatile flow system with a modeled ascending aorta and a regurgitant
      aortic valve orifice was developed. The model could generate "aortic
      regurgitation-like" waveforms through the use of an electrically controlled
      valve. The regurgitant flows through the orifice (8.5 to 28.1 mL/beat) were
      measured by an ultrasound flowmeter; they were also calculated in the ascending
      aorta 1.0 cm above the orifice by the automated cardiac flow measurement method,
      which integrated spatially distributed digital flow velocity data through
      "diastole." Calculated regurgitant volumes measured with the low color Doppler
      filter (5.4 cm/s) agreed well with those measured with the flowmeter (r=.99, P <
      .001, mean difference=2.2+/-3.7 mL). However, the regurgitant volume was
      underestimated when 2 higher filter settings were used (9.6 and 10.9 cm/s).
      Although there was no significant difference in mean volume, higher frame rate
      (19 frames/s) provided more reproducible results with smaller standard deviation
      as compared with lower frame rate (7 frames/s). CONCLUSIONS: This new automated
      cardiac flow measurement method appears to be promising for semiautomatic
      quantification of aortic regurgitant volume. Appropriate choice of filter setting
      and high frame rate assists reliable data acquisition.

PMID- 9758381
TI  - Transthoracic echocardiographic measurement of coronary artery diameter:
      validation against quantitative coronary angiography.
AB  - There has been no in vivo validation of the use of transthoracic echocardiography
      to measure distal left anterior descending coronary artery (LAD) diameter. We
      therefore undertook transthoracic echocardiography on 65 male patients
      immediately before cardiac catheterization to compare echocardiographic and
      angiographic findings. The distal LAD was successfully imaged in 41 (63%)
      patients; 29 of these had an angiographically normal distal LAD as assessed by an
      independent cardiologist and formed the study group. Transthoracic
      echocardiographic and quantitative coronary angiographic measurements of distal
      LAD diameter were made. Echocardiographic measurements ranged from 0.14 to 0.28
      cm (mean 0.20 cm). Angiographic results ranged from 0.12 to 0.28 cm (mean 0.195
      cm). Correlation between techniques was good (r=.925). The maximum discrepancy
      between transthoracic echocardiography and quantitative coronary angiography was
      0.03 cm. Limits of agreement were +0.032 to -0.024 cm. We conclude that
      transthoracic echocardiography is a valid technique for measurement of distal LAD
      diameter.

PMID- 9758382
TI  - Survey of hospital-based echocardiography services.
AB  - A survey of policies and procedures for delivering echocardiography services in
      acute-care hospitals in the state of Illinois was performed to define the present
      state of the art. Indications for ordering an echocardiographic study were
      relatively uniform, as the normalized, annual number of transthoracic
      echocardiograms performed were similar throughout the state. Training criteria
      for becoming an echocardiography physician-interpreter, although published by
      national societies, were variable. Sonographer training was predominantly
      provided through an informal apprenticeship system, and both physician and
      sonographer continuing medical education requirements were minimal.
      Echocardiogram reports were primarily generated by free text dictation or
      transcription and were transmitted to the ordering physician in a variety of
      ways. There was no agreement regarding what diagnosis constituted a "stat value."
      National specialty societies such as the American College of Cardiology and the
      American Society of Echocardiography should address these issues to assist
      physicians and hospitals in improving their echocardiography services.

PMID- 9758383
TI  - Severely reduced left atrial appendage function: a cause of embolic stroke in
      patients in sinus rhythm?
AB  - Recently, attention has been focused on transesophageal echocardiographic
      detection of left atrial appendage function to assess of risk of thrombus
      formation because of potential benefit of anticoagulation therapy. However, most
      of these studies have been conducted in patients with atrial fibrillation or
      mitral valve disease. In this article we review cases of 2 patients without
      valvular disease who had embolic stroke in sinus rhythm. Transesophageal
      echocardiography revealed thrombi in the left atrial appendage in both patients.
      The left atrial appendage function in these patients was compared with that in
      patients with chronic atrial fibrillation and a control group in sinus rhythm.
      Left atrial appendage function in the patients with stroke and sinus rhythm was
      significantly lower than that of patients in the control group in sinus rhythm (P
      < .001) and was similar to the appendage function in patients with chronic atrial
      fibrillation. These observations provide further evidence that the finding of
      reduced left atrial appendage function can be a cause of stroke in patients with
      sinus rhythm even in the absence of mitral valve disease. Reduced left atrial
      appendage function may identify patients with unexplained stroke who should
      receive anticoagulation therapy even in the absence of detectable appendage
      thrombi.

PMID- 9758384
TI  - Prenatal diagnosis of abnormal persistence of the right or left umbilical vein:
      report of 4 cases and literature review.
AB  - Four cases of prenatally diagnosed abnormal persistence of an umbilical vein are
      presented. Of the 4 cases, 2 are in association with congenital heart disease, 2
      are in the setting of abdominal visceral situs inversus, and 1 is with
      extrahepatic persistence of an umbilical vein. Whereas persistent right umbilical
      vein may occur in 0.2% to 0.4% of fetuses undergoing screening prenatal
      ultrasonography, reports of an extrahepatic course are rare. A review of the 62
      reported cases of prenatally diagnosed abnormally persistent umbilical vein
      revealed 9 fetuses (15%) with a congenital cardiovascular malformation, of which
      6 were significant enough to likely require surgery. Other organ system
      malformations were present in 9 patients (15%). The prevalence of congenital
      cardiovascular malformations was 3 (7%) of 42 when combining 2 large series that
      were relatively unbiased for referrals for possible heart disease. Detailed
      evaluation by ultrasonography and fetal echocardiography should be used for
      prenatally diagnosed cases of abnormal persistence of an umbilical vein.

PMID- 9758386
TI  - Outcomes research review.

PMID- 9758385
TI  - Bifid left atrial appendage with thrombus: source of thromboembolism.
AB  - Three patients with embolic events were found on transesophageal echocardiography
      (TEE) to have bifid left atrial appendage (LAA). In these patients, large mobile
      thrombi were found only in the posterior limb of the appendage. The best views to
      demonstrate the posterior limb were between 85 and 155 degrees from the
      transverse plane with the use of a multiplane TEE probe. To avoid overlooking
      this pathologic condition, we recommend that complete evaluation of the LAA
      should include rotation of the TEE transducer up to 155 degrees from the
      transverse plane.

PMID- 9758387
TI  - Modeling of spreading cortical depression using a realistic head model.
AB  - Barkley and colleagues in 1990 reported large amplitude waves (LAWs) in time
      series magnetoencephalography (MEG) recordings from migraine patients and
      inferred that these LAWs arose from spreading cortical depression (SCD). SCD
      propagates slowly across the cortex in all species in which it has been observed.
      Previously, we reported that LAWs could be simulated and compared with the
      recorded signals using the four-sphere model (Wijesinghe and Tepley 1997). We
      showed that LAWs could arise from the propagation of SCD across a sulcus. In this
      paper, we model LAWs using a realistically shaped head model based on magnetic
      resonance images (MRI) (Roth et al. 1993). Simulated signals using this model are
      similar to the recorded signals. In this model, current dipoles represent the
      excitable neurons in the cortex and magnetic fields created by these individual
      dipoles are calculated. The magnetic field arising from the excited area of
      cortex is obtained by summing the fields due to these individual dipoles.

PMID- 9758388
TI  - Application of the directed transfer function method to mesial and lateral onset
      temporal lobe seizures.
AB  - The directed transfer function (DTF) method is a multichannel analysis based on
      an autoregressive model that detects flow of seizure activity. This report
      extends the application of the DTF method to compare patterns of flow of seizures
      with different sites of origin. Analysis of a seizure originating from mesial
      temporal structures is compared with a seizure originating from lateral temporal
      neocortex; both complex partial seizures were recorded with intracranial
      electrodes that combine subdural grid arrays and depth electrodes. The DTF method
      has the potential to determine patterns of flow of activity, including periods
      when visual analysis of the intracranial ictal EEG may not allow for definitive
      source localization. The extension of the DTF analyses into integrated DTF (IDTF)
      formats is also illustrated. When activity of a relatively discrete frequency can
      be identified, the IDTF analysis facilitates display of patterns of flow of this
      selected activity.

PMID- 9758389
TI  - Spatial EEG synchronisation over sensorimotor hand areas in brisk and slow self
      paced index finger movements.
AB  - The changes of spatial EEG synchronisation during brisk and slow voluntary self
      paced movements of the right and left index finger were analysed in 12 right
      handed and 11 left-handed subjects. EEG was recorded from the left and right
      sensorimotor area using 24 closely spaced electrodes. A novel measure of spatial
      EEG synchronisation, omega-complexity, was computed separately for the left and
      right sensorimotor area in 64 overlapping one-second epochs representing 4.5 s of
      the pre-movement and 3.5 s of the post-movement period. Omega-complexity was
      higher, hence spatial synchronisation was lower, in slow than in brisk movements,
      especially in the right-handed. A sustained increase of omega-complexity was
      observed during execution of a slow movement. A decrease of omega-complexity
      which was often associated with a brief burst of spatially synchronised 10-Hz
      oscillations occurred at the onset of extensor muscle contraction. We suggest
      that increased spatial EEG synchronisation at movement onset may prevent
      "spillover" of excitation from the sensorimotor hand area to other cortical
      regions. During movement, the cortical neuronal assemblies subserve distinct,
      specialised functions manifesting in increased omega-complexity.

PMID- 9758390
TI  - Left frontal EEG coherence reflects modality independent language processes.
AB  - Previous studies showed that distinct components of higher cognitive processes
      like memorizing of words could be correlated with changes in different frequency
      bands of the human EEG. This study was designed in order to find out if 1) some
      frequency bands show power and coherence changes only due to the modality of
      presented stimuli (either auditory or visual) and 2) if other frequency bands
      show modality independent effects which should reflect real cognitive-linguistic
      differences between word classes (either concrete and abstract nouns). EEG was
      recorded from sixteen right-handed females which had to memorize auditorily and
      visually presented concrete and abstract nouns. Results show the alpha-1 band to
      reveal no differences between word classes but demonstrate an influence of
      modality of stimulus presentation. The only modality independent differences
      between concrete and abstract noun processing were found in the delta, theta and
      beta-1 band at left frontal electrodes.

PMID- 9758391
TI  - Addressing misallocation of variance in principal components analysis of event
      related potentials.
AB  - Interpretation of evoked response potentials is complicated by the extensive
      superposition of multiple electrical events. The most common approach to
      disentangling these features is principal components analysis (PCA). Critics have
      demonstrated a number of caveats that complicate interpretation, notably
      misallocation of variance and latency jitter. This paper describes some further
      caveats to PCA as well as using simulations to evaluate three potential methods
      for addressing them: parallel analysis, oblique rotations, and spatial PCA. An
      improved simulation model is introduced for examining these issues. It is
      concluded that PCA is an essential statistical tool for event-related potential
      analysis, but only if applied appropriately.

PMID- 9758392
TI  - Functional hemispheric asymmetry assessment in a visual language task using MEG.
AB  - We used magnetoencephalography (MEG) to assess the degree of hemispheric
      activation in eleven normal, right-handed subjects with no history of
      neurological disorder or learning disability during performance of a word- and a
      face-recognition tasks. Neuromagnetic activity was recorded using a whole-head
      system, and the sources of the recorded magnetic fields were modeled as single
      equivalent current dipoles. Early (<200 msec) cerebral activation, defined by the
      number of dipoles identified by the data-fitting algorithm, was localized in the
      occipital cortex during both tasks, as expected. During the language task, the
      extent of the later (>200 msec) cerebral activation was approximately double in
      the left hemisphere in almost all subjects, involving temporal and
      temporoparietal areas. In contrast, during the face-recognition task, the
      corresponding activation was mostly symmetrical across the two occipital lobes,
      also involving the posterior-inferior aspect of the right temporal lobe. Our
      results suggest that the MEG is a suitable method of assessing noninvasively
      hemispheric specialization for language.

PMID- 9758393
TI  - The relationship between satisfaction with mouth and number and position of
      teeth.
AB  - A number of studies have suggested that many people are satisfied with less than
      28 natural teeth. This review assesses the evidence. The main conclusion was that
      less than a complete dentition can satisfy oral functional needs. Missing
      posterior teeth were not very important from a subjective aspect. The demand for
      replacement of missing teeth is related to the position of missing teeth. Most
      studies agree that individuals were more concerned about missing anterior teeth
      and having anterior rather than posterior teeth replaced. Aesthetics is more
      important than function for a great majority of individuals. However, certain
      socio-demographic factors, such as age, can change the subjective need for
      replacement of missing teeth. Some studies have assessed the social and
      psychological impacts on oral health status. The position of missing teeth was
      assessed, in terms of groups of missing teeth, anterior or posterior, that would
      affect an individuals' subjective need for replacement by partial prosthesis.
      Large numbers of people that have free end removable partial dentures made do not
      wear them because subjective needs are lower than normatively determined needs
      for replacement of missing teeth. Some studies have proposed alternatives to the
      replacement of missing teeth, such as the shortened dental arch concept.

PMID- 9758394
TI  - Relationship between juvenile bruxing and craniomandibular dysfunction.
AB  - A longitudinal study was conducted over 5 years to investigate the relationship
      between juvenile bruxing and craniomandibular disorders. A total of 150 bruxers
      between the ages of 6 and 9 years were examined for oral parafunctions and TMJ
      symptoms. Of these, 126 were re-examined for the same signs and symptoms after 5
      years. The results showed that only 17 individuals had retained their bruxing
      habit. In common with other studies, we found that symptoms reduced with age. It
      was concluded that juvenile bruxing was a self-limiting condition which does not
      progress to adult bruxism and which appeared to be unrelated to TMJ symptoms.

PMID- 9758395
TI  - Comparison of marginal sealing ability of new generation bonding systems.
AB  - The purpose of this in vitro study was to evaluate the enamel and dentine
      marginal sealing ability of four new generation composite bonding systems. Two
      Class V preparations, which were solely in enamel and dentine/cementum, were made
      on the buccal surfaces of 96 freshly extracted molar teeth. The teeth were
      randomly divided into four groups of 24 and restored with composite resin (Silux
      Plus) utilizing the following bonding systems: Scotchbond Multi-purpose (SB),
      Fuji Bond LC (FB), Prime & Bond 2.0 (PB) and Bisco One-step (BC). The
      restorations were finished immediately after photo-polymerization and stored in
      saline at 37 degrees C for 1 week. Half of the specimens in each group were then
      thermally stressed for 500 cycles. All restorations were then subjected to dye
      penetration testing, sectioned and scored. Results revealed no statistically
      significant difference (P < 0.05) in dye penetration scores for the different
      bonding systems with the exception of leakage at the dentine margins of thermally
      stressed specimens where FB exhibited significantly better sealing ability
      compared with the other bonding systems and BC exhibited significantly less
      leakage than PB. The marginal seal of 'one-step' (PB and BC) and resin-modified
      glass-ionomer (FB) bonding systems appear to be as effective as 'two step'
      systems like SB. Thermal stresses had some influence on marginal seal but this
      was both product and tissue specific.

PMID- 9758396
TI  - CMDME (curved mesh diagram of mandibular excursion) method for visualization and
      diagnosis of mandibular movement.
AB  - The CMDME (curved mesh diagram of mandibular excursion) method was developed for
      easy visualization and diagnosis of mandibular movement. This method uses
      measured mandibular movement to produce a diagram of the range, shape, and
      inclination of mandibular excursion in three dimensions using any arbitrary
      landmark of the mandible. First, the mandibular movement of a subject was
      measured by an opto-electronic movement analysis system capable of measuring
      mandibular movement with six degrees-of-freedom at a sampling frequency of 100
      Hz. For the measurement, the subject was initially instructed to perform four
      repetitions of mandibular excursion at will, with tooth contact, each lasting 30
      s. A total of 12 000 positions of the mandible were thus obtained. Secondly, an
      attempt was made to match these positions to intersection points (0.1 mm apart)
      of a CMDME (i.e. mesh) for arbitrary mandibular landmarks with intercuspal
      position at the origin. The CMDME method can visualize mandibular excursion, and
      can be used to compare several landmarks, different subjects, or different times.
      This makes this method an effective diagnostic tool for mandibular movement.

PMID- 9758397
TI  - Complications and primary failures related to fixed metal ceramic bridge
      prostheses made by dental students.
AB  - Porcelain fused to metal provides better aesthetics in fixed partial dentures
      than veneers with gold-resin that were used formerly. The aim of our study was to
      evaluate complications and primary failures of fixed metal ceramic bridge
      prostheses made by dental students. We studied 61 patients (32 women, 29 men,
      mean age 49 years, range 28-73 years) treated during years 1990-1993. Data were
      collected from the patient files. Altogether 82 bridges were made (mean 4.1
      units, range 2-6), 221 abutments (mean 2.7, range 2-6) and 136 pontics (mean 1.6,
      range 1-4). Forty-seven cast cores were used in 29 bridges (mean 0.4 cores, range
      1-3) and semiprecious attachments as an extra attachment in two bridges. Seven
      teeth were extracted due to complication and/or failure during endodontic
      treatment and root canal perforation during preparation. In two cases the
      abutment tooth was fractured by removing the old crown. Four unsuccessful bridges
      were remade and in seven cases the firing of porcelain was renewed. The study
      concludes that most common failures of fixed metal ceramic bridges made by dental
      students occur during root canal preparation of abutment teeth.

PMID- 9758398
TI  - The variability of bite force measurement between sessions, in different
      positions within the dental arch.
AB  - The effect of measuring bite force with different patterns of transducer on
      different occasions was studied. Maximum voluntary bite force was measured in
      eight volunteers. Three transducer positions, each with a different pattern of
      transducer, were used; between the anterior teeth, between the second premolar
      and the first molar on one side and between the second premolars and first molars
      on both sides. Visual feedback of force was provided. Two sets of five maximum
      clenches were recorded with a rest period in between. This sequence was repeated
      for each transducer and the experiment was repeated on three different days. The
      highest forces were measured with the bilateral posterior transducer (mean 580 N,
      s.d. 235) and the lowest on the anterior transducer (mean 286 N, s.d. 164). The
      standard deviations of the bite force mean values were used as an indication of
      the variability and were subjected to a non-parametric anova (Kruskal-Wallis).
      The forces recorded with each transducer position were significantly different
      between the transducers (P < 0.01) and the maximum bite force showed least
      variability when measured between the posterior teeth on one side only. There was
      little difference in bite force between the three different sessions (P > or =
      0.05) when measured in the same position within the dental arch, whichever of the
      three positions that may be.

PMID- 9758399
TI  - Macroscopic osseous changes in the temporomandibular joint related to dental
      attrition in Japanese macaque skull.
AB  - The purpose of this study was to investigate the relationship between osseous
      changes in the temporomandibular joint (TMJ) and dental attrition in the Japanese
      macaque. One hundred and thirty Japanese macaque skulls (54 male and 76 female)
      from animals which had been bred in the same environment, were randomly sampled
      from a collection at the Primate Research Institute of Kyoto University. The age
      at death had been recorded in all cases. TMJ osseous changes were independently
      evaluated by three examiners, and were defined as an irregular surface or a
      perforated compact bone layer with a markedly irregular surface on either the
      temporal or condylar components. Age was a significant factor in predicting TMJ
      osseous changes (P < 0.001). A strong relation was observed between age and
      dental attrition (P < 0.001), while dental attrition was not a significant factor
      in predicting TMJ osseous changes (P = 0.334). The prevalence TMJ osseous changes
      in male animals was slightly higher than in females (P = 0.057). The results of
      this study suggest that osseous changes in the macaque TMJ are mainly related to
      age, not to dental attrition.

PMID- 9758400
TI  - Bond strength of photocured composite resin facings: clinical versus laboratory
      procedures.
AB  - The tensile strengths of laboratory versus clinical photocured composite resins
      have been investigated. Metal surfaces were bonded to photocured composite resin
      by either retentive beads, Sebond or Silicoating. The bond strengths were
      measured by an Instron machine and the fracture sites observed. Following repair
      with the adhesives Dentacolor Opaquer, Fusion and Cover up 2, the Instron
      measurements were repeated. The metal/facing bond strength was the highest in
      samples fabricated by the Silicoating technique, the bond strength exceeding the
      cohesive forces in the composite resin facing. The tensile strengths of
      metal/facing bonded by Sebond and retentive beads were similar. Fractures that
      include the facing and partially reveal the metal are the least resistant to
      tension after repair. Renewal of the Opaque layer and completion of the facing is
      superior to any of the repair methods used in this paper. The original fracture
      point is the weakest after repair. All the repair kits tested were inferior to
      the original restoration materials.

PMID- 9758401
TI  - Effects of different surface treatment methods on the bond strength of composite
      resin to porcelain.
AB  - In this study failures of composite resin/ porcelain interfaces under shear
      loading were examined. Porcelain firing were made onto metal cylinders and
      porcelain surfaces were roughened with burrs or treated with hydrofloric acid gel
      and/ or sandblasted with a Microetcher. Two silane coupling agents were used in
      five groups, each of which had 22 samples. All of the treated samples were
      restored with a hybrid-type composite resin. Then each group was divided into two
      subgroups according to storage times of 24 h and 30 days. After thermocyling the
      samples which were stored for 30 days, all of the groups were subjected to shear
      force at the composite resin/porcelain interface until fracture occurred. The
      results showed that there were differences both in the 24-h and 30-day storage
      period bond strengths between the various surface treatment methods. The samples
      treated with all three of the Microetcher, hydrofloric acid and silane exhibited
      the highest shear bond values after 24 h storage, followed by the
      microetched/silane and the hydrofluoric acid/silane groups (F: 570.31, P: 0.00).
      After 30 days, the highest mean shear bond strength values were again with
      samples treated by all three processes. The storage period and thermocycling
      decreased the bond strength of samples, however, there was a significant
      difference among groups (F: 1388-55, P: 0.00). Silane pre-treatment of porcelain
      was important as the mean bond strength of sandblasted/etched specimens were
      significantly lower than the other groups which were treated mechanically, in 24
      h. Sandblasting seems to have little effect on the bonding. The comparison of 24
      h and 30-day samples have also significant difference (F: 91.4376, P: 0.00).

PMID- 9758403
TI  - The effect of diabetes mellitus on histopathological changes in the tissues under
      denture base and without mechanical pressure.
AB  - Histopathological changes in the tissues under a denture base were studied with
      respect to the difference between diabetic and normal rats. Diabetes mellitus was
      induced in Wistar rats by streptozotocin. The experimental denture base was
      designed to make contact with the palatal mucosa without any continuous nor
      masticatory pressure. Histopathological observation periods were 1, 2, 4, 8, 12
      and 20 weeks after the insertion of the denture base. Histopathological
      examination revealed that only the transient slight proliferative reaction
      observed in mucosal epithelium under a denture base in normal non-diabetic rats,
      was lessened by induced diabetes mellitus. Moreover, covering the palatal mucosa
      with a denture base without any continuous nor masticatory pressure and with the
      maintenance of mucosal cleanliness under it and of the denture itself, did not
      cause any inflammatory change or bone resorption in the tissues under the base.

PMID- 9758402
TI  - Physical mechanisms involved in the genesis of temporomandibular joint sounds.
AB  - Several different mechanisms are potentially capable of generating sounds in the
      temporomandibular joint (TMJ). These include impact, sliding and stick-slip
      friction, fluid dynamic effects and the release of elastic strain energy. It is
      the aim of this paper to provide a framework with which to separate sounds
      resulting from the different underlying causes. Each mechanism is described and
      its relevance to TMJ sounds and clinical significance discussed. Since it is not
      possible to observe these mechanisms in vivo the arguments are based mainly on
      analogies which are used to make predictions of the characteristic acoustic
      signatures of the sounds produced by these different mechanisms. In particular
      the changes in the characteristics of the sounds as parameters such as mandibular
      speed and loading are stressed. It is suggested that single short duration sounds
      (clicks) are due to impact, multiple short duration sounds (creaks) to stick-slip
      friction and defects of form and long duration sounds (crepitus) to simple
      sliding friction. Several other mechanisms which have no obvious clinical
      significance but which are capable of producing similar sounds are also described
      and methods of distinguishing them from the sounds that do have clinical
      implications are discussed.

PMID- 9758404
TI  - The effect of parafunction on condylar asymmetry in patients with
      temporomandibular disorders.
AB  - This study was undertaken to examine the relationship between condylar asymmetry
      and parafunction in patients with temporomandibular disorders (TMD). Twenty-eight
      patients with TMD and parafunction and 30 patients with TMD but no parafunction
      were examined. A panoramic radiograph was obtained for each patient and from this
      the condylar asymmetry determined. The group with parafunction showed a
      significantly (P < 0.005) higher asymmetry index than did the group with no
      noticeable parafunction. Patients were grouped into the following age ranges: 10
      19 years, 20-29 years, 30-39 years, and 40 + years. The mean asymmetry index was
      determined for each age range for both groups of patients. The group of patients
      with TMD and parafunction had a higher mean asymmetry index in all the age ranges
      studied. This suggests that muscle hyperactivity may be a factor in the increased
      asymmetry found in patients with TMD.

PMID- 9758405
TI  - Effect of denture thickness on tooth movement during processing of complete
      dentures.
AB  - In this investigation the effect of denture thickness on tooth movement during
      processing of complete dentures was studied. A maxillary cast from a patient was
      duplicated to obtain 10 identical casts. Base plates were constructed on five
      casts using 1.25 mm thick wax. Base plates were constructed on the other five
      casts using 2.5 mm thick wax. Teeth were placed on the ridge of each cast and a
      TMS pin was placed vertically, upright, in each tooth. The dentures were
      invested, cured, decasted, finished and polished. Each denture was radiographed
      immediately before processing, after deflasking, on removal from the cast and
      after finishing and polishing using a standard technique. The radiographs were
      digitized using an Eikonix image digitizer. The results showed that there were
      significant variations in tooth movement between thick and thin denture bases.
      Also an increase in the molar-to-molar distance was found in both the thin and
      thick dentures but the magnitude of tooth movement was more in thick dentures.

PMID- 9758406
TI  - CD8+ cytolytic T lymphocytes and the skin.
AB  - T lymphocytes show a special affinity for the skin. Although the roles played by
      the CD4+ population of T lymphocytes in immunodermatology were so far actively
      investigated, much less is known about the roles played in the skin by CD8+
      cytolytic T lymphocytes (CTL). The activity of CD8+ CTL in the
      immunodermatological context, however, is likely to be most important; the immuno
      biology itself of CD8+ CTL, moreover, although far from being fully understood,
      shows intriguing characteristics. Immunophenotype, function and cytokine profile
      of CD8+ CTL are overviewed in the first section of this review. Phenotypically,
      not only CD8+ CTL can be subdivided into CD8+ CD28+ CD11b- and CD8+ CD28- CD11b+
      subsets, but also an up-to-now undetected CD8+ CD28- CD11b- subset does exist.
      Functionally, not only "cytotoxic" but even "suppressor" subpopulations have been
      shown to exert cytolytic capabilities indeed, and "suppression" itself may be due
      to such a lytic capacity. According to cytokine synthesis, CD8+ CTL can be split
      into Tc1 and Tc2 subsets, each able to influence specific patterns of immune
      responses. The impact of CD8+ CTL in immunodermatology, overviewed in the second
      section of the current review, is crucial. The pathophysiology of inflammatory
      dermatoses is deeply influenced by the activity of CD8+ CTL: e.g., CD8+ CTL
      within psoriatic epidermis are possibly associated to the persistence of
      psoriatic lesions not undergoing resolution; on the other hand, in late lesions
      of lichen planus CD8+ CTL predominate, thus explaining presumably both the
      cytolytic attack against keratinocytes and the modulation of the inflammatory
      reaction up to the final resolution of the lesions, Tc1 cells are decreased in
      atopic dermatitis, and such a decrease can account both for IgE overproduction
      and for development of infections. Finally, CD8+ CTL can sustain against
      cutaneous viruses/tumors cytolytic immune responses not only of secondary but
      even of primary type, i.e. induced by Langerhans cells/dendritic cells either
      transfected or pulsed with skin virus/tumor-associated antigens, thus allowing
      the production of vaccines against cutaneous viral/neoplastic diseases.

PMID- 9758407
TI  - The millennium criteria for the diagnosis of atopic dermatitis.
AB  - Atopic dermatitis forms an active area of basic and clinical research, where
      important new knowledge about genetics and immunopathogenesis has surfaced over
      the past years, and where simultaneous development of new and innovative
      therapies is under way. However, the inclusion of any patient in an atopic
      dermatitis study, whether it is on its genetics, pathogenesis or therapy,
      requires a diagnosis which is irrefutable. Since there is no simple and also no
      complicated laboratory procedure to reach a diagnosis of atopic dermatitis,
      different sets of clinical criteria have been developed for the purpose of making
      the diagnosis uniformly in different studies as well as in different study
      centers. The most commonly used are Hanifin and Rajka's set of diagnostic
      features, which have major and minor clinical criteria to be fulfilled in order
      to establish a diagnosis of atopic dermatitis. Recent developments in the
      immunology of atopy have clearly established the major abnormality in this
      syndrome, the preferential production of allergen-specific IgE. In this
      contribution, it is suggested that the presence of such antibodies in a given
      patient should be a mandatory criterium for the diagnosis of atopic dermatitis.
      Such a diagnostic test however establishes a diagnosis of atopic syndrome, not
      atopic dermatitis. Thus, for atopic dermatitis we have to rely, for the time
      being, on additional clinical criteria. The clinical features described in the
      literature are critically evaluated, and it is suggested that in addition to the
      mandatory presence of allergen-specific IgE, 2 of 3 principal criteria (pruritus,
      typical morphology and distribution, chronic or chronically relapsing) should be
      present for such a diagnosis. Finally, the minor features originally described by
      Hanifin and Rajka and later evaluated by others are revised and divided over 4
      subcategories; a) related to subclinical eczema; b) related to dry skin; c) extra
      skin folds; and d) ophthalmological pathology. They are suggested to be used as
      additional criteria only, needed when clinical suspicion is high but the new
      mandatory and principal diagnostic criteria described here are inconclusive. For
      study purposes, we suggest that the mandatory and principal criteria are
      sufficient. They are now evaluated and validated in ongoing atopic dermatitis
      treatment studies.

PMID- 9758408
TI  - Most chronic urticaria is food-dependent, and not idiopathic.
AB  - Although chronic urticaria is generally thought to be mostly idiopathic, we have
      recently provided convincing evidence that in the majority of patients, food
      ingredients provoke the symptoms and sustain the disease. On a diet largely
      avoiding preservatives, dyes and natural pseudoallergens, 73% of patients
      experienced remission of more than 6 months duration, starting within the first 3
      weeks after initiation of the diet. This response rate is clearly higher than the
      reported 24% spontaneous remission rate over the same time period. The
      specificity of the dietary effect was proven 1) by double-blind provocation with
      pureed pseudoallergen-low versus -rich food and 2) by induction of a clinical
      response to a 3-week diet low in pseudoallergens, but not to a standard diabetes
      diet in 3 patients studied in a double-blind crossover design. On double-blind,
      placebo controlled oral provocation, only 18% of diet-responsive patients reacted
      to known food preservatives and dyes, but 71% to pureed tomatoes and 44% to their
      steam extracts. These findings identify naturally occurring pseudoallergens in
      food as major elicitors of chronic urticaria. In contrast, autoantibodies against
      Fc epsilonRIalpha have been identified in only about 30% of chronic urticaria
      patients, and evidence for their truly causative role is still lacking since
      therapeutic measures work in patients irrespective of the presence or absence of
      the autoantibodies. For both food intolerance and Fc epsilonRIalpha
      autoantibodies in chronic urticaria, the associated pathomechanisms are however
      still in need of clarification. Meanwhile, the diet-responsiveness in the
      majority of patients opens new perspectives for the management of chronic
      urticaria.

PMID- 9758409
TI  - What controls melanogenesis?
AB  - The pigments eumelanin and pheomelanin are the visually most striking products of
      specialized neural crest-derived cells (melanocytes), and provide color to both
      epidermis and hair shafts. While the intriguing and controversial biological
      functions of these multifaceted heteropolymers will be discussed in a later
      feature, here it is explored how their generation (melanogenesis) is controlled.
      For decades, this has been the object of much controversy, the salient features
      of which are delineated in the following contributions.

PMID- 9758410
TI  - Release of monocyte chemoattractants by polymorphonuclear leukocytes stimulated
      by their adhesion to stratum corneum opsonized via complement activation,
      measured with a human acute monocytic leukemic cell line, THP-1.
AB  - Stratum corneum (SC) exposed to living tissues, induces inflammation
      characterized by the formation of mixed cell granulomas consisting of
      infiltrative polymorphonuclear leukocytes (PMNs) and monocytes/macrophages. In
      this study, to clarify the mechanism for the later monocyte accumulation in SC
      induced granulomas, we evaluated monocyte chemotactic activity induced by PMNs
      treated with serum-opsonized SC by using a human acute monocytic leukemic cell
      line, THP-1. When the supernatant was obtained from a PMN suspension cultured
      with opsonized plantar SC, higher THP-1 chemotactic activity was detected as
      compared with that cultured with non-opsonized SC. Although some concentrations
      of the chemokines, MIP-1alpha and MIP-1beta, were detected in supernatants
      obtained from the PMN suspensions cultured with plantar SC than in the control
      suspensions of PMN alone, their production by PMN was not influenced by the
      opsonization procedure. In contrast, MCP-1 was found to be secreted from PMN
      suspensions constitutively, showing no correlation to this THP-1 chemotactic
      activity. Moreover, HPLC analysis of PMN suspensions indicated that factors with
      far higher molecular weight values than these chemokines are involved in the
      chemotaxis of THP-1 cells.

PMID- 9758411
TI  - Decreased interleukin-7 and transforming growth factor-beta1 levels in blister
      fluids as compared to the respective serum levels in patients with bullous
      pemphigoid. Opposite behavior of TNF-alpha, interleukin-4 and interleukin-10.
AB  - This study analyzes both the blister fluid (BF) and serum levels of IL-7 and TGF
      beta1 in samples from 18 patients affected with bullous pemphigoid (BP). These
      cytokines clearly present lower concentrations (P<0.001) in BFs than in the sera
      (1/20 and 1/2, respectively). In contrast, TNF-alpha, IL-10 and IL-4 present
      increased amounts in BFs that were 12, 12 and 17-fold, respectively. Eighteen
      sera (and 10 suction BF) from normal individuals were also employed as control.
      Normal sera presented significantly lower serum IL-7 concentrations than BP,
      while no significant TGF-beta1 variations were observed between normal and
      pathologic serum samples. In addition, the serum levels detected in BP patients
      were significantly correlated with disease intensity (r=0.64, P=0.003, evaluated
      as the number of blisters/erosions for each patient) as well as with the
      peripheral B-lymphocyte counts (r=0.80, P<0.001) and antibodies directed against
      the basement membrane zone (r=0.65, P<0.005). Although a clear explanation of
      this phenomenon is lacking, the data presented in this report agree with a strong
      decrease of IL-7 production at the local level (keratinocyte is known to produce
      IL-7 and the latter is known to be down-regulated by IL-10, and in other models
      also by TGF-beta1 and IL-4, whose levels are elevated in BP BFs) as opposed to an
      increased peripheral release of the same modulator. The IL-7 reduction may have a
      biological relevance in controlling a chronic, progressive disease.

PMID- 9758412
TI  - The influence exerted by cutaneous ligands in subjects reacting to nickel sulfate
      alone and in those reacting to more transition metals.
AB  - To study the influence exerted by cutaneous ligands in nickel reactions we have
      evaluated the patch tests responses to 4 aqueous nickel salts (sulfate, chloride,
      nitrate, acetate) able to form different complexes with different geometry. Two
      groups of respectively 71 subjects who previously reacted only to nickel sulfate
      5% petrolatum (pet) and of 30 subjects who previously reacted to nickel sulfate
      5% pet and to at least 1 other transition metal, were simultaneously repatch
      tested to 200 microg of Ni++ contained in nickel sulfate in pet and to 47 microg
      of Ni++ contained in 4 different aqueous nickel salts. Another 2 groups of 25
      subjects with the same characteristics were simultaneously repatch tested to 200
      microg of Ni++ in pet and to 12 microg of aq Ni++ as in the first 2 groups.
      Visual score, total score, and mean value of the reactions were utilized in
      evaluating the degree of the responses. On testing to 200 microg of Ni++ in pet
      all the subjects were able to give positive responses. Whilst a higher percentage
      of the responses of 2+ degrees was found in subjects reacting to nickel sulfate
      5% pet alone, a higher percentage of responses of 3+ degrees was observed in
      subjects reacting to more transition metals. On testing to 47 and 12 microg of
      aqueous Ni++ a large variability of responses to the single salts was observed in
      all the subjects. However, in subjects reacting to more metals there were either
      a greater number of multiple responses to 3 or 4 salts or responses stronger than
      those found in subjects reacting to nickel sulfate alone. Although patch testing
      cannot give us complete information about the degree of previous exposure, the
      results arising from the tests seem to demonstrate that the subjects allergic to
      nickel and other transition metals are more reactive than the subjects allergic
      only to nickel to the application of the same amounts of Ni++ contained in
      different salts. When considering the QSAR model, the difference in the
      sensitizing potential of the metal at the same penetration properties can depend
      on the possibility of combining with specific ligands. Therefore, it is likely
      that in subjects reacting to more metals there is a more uniform availability of
      cutaneous ligands which conditions the formation of complexes more immunogenic.
      The arising inflammatory reaction in these cases leads to a stronger but less
      specific response.

PMID- 9758413
TI  - Expression of the anhidrotic ectodermal dysplasia gene is reduced in skin cancer
      coinciding with reduced E-cadherin.
AB  - X-linked anhidrotic ectodermal dysplasia (EDA) is characterized by defects in the
      development of hair, teeth, and sweat glands. We have recently cloned the gene
      for EDA by positional cloning. The EDA gene encodes a transmembrane protein with
      a putative role in epithelial mesenchymal interactions. Since EDA could play a
      role in cell-cell or cell-matrix adhesion, acantholytic skin diseases and several
      types of non-invasive and invasive skin cancers were studied using in situ
      hybridization. Because of the observation that the promoter region of the EDA
      gene contains a binding site for LEF-1, which is involved in the signaling
      through E-cadherin/beta catenin complex, we compared the expression of EDA with
      immunolocalization for E-cadherin (E-CD). EDA expression during hair growth
      cycle, in benign adnexal tumors, and neuroectoderm-derived nevus cells was also
      examined. Our findings indicate that EDA expression is less abundant in malignant
      tumors, including basal and squamous cell carcinomas and melanoma, and in
      acantholytic keratinocytes compared to normal epidermis. The reduction in
      expression also coincides with diminished E-CD staining in all malignant cell
      types and in acantholytic cells. Our results suggest that EDA protein functions
      in the regulation of epithelial cell contacts and that it may be associated with
      the E-CD signaling pathway.

PMID- 9758414
TI  - CD24 expression on human keratinocytes.
AB  - CD24 or Nectadrin is a cell surface glycoprotein expressed in pre-B lymphocytes,
      T lymphocytes, neurons, muscle cells and carcinoma cells. Its function is not
      completely known, but it has been suggested that it is involved in cell adhesion
      and signalling. CD24 has recently been identified as the human molecule
      homologous to the murine heat-stable antigen (HSA). HSA is expressed by murine
      keratinocytes and delivers costimulatory signals in T-cell activation. Long-term
      cultures of normal human keratinocytes (HKC) were obtained from skin of human
      female breast sections and either left untreated or were treated with phorbol-12
      myristate-13-acetate (PMA) at 10-100 ng/ml, calcium 0.5-2 mM or IFN-gamma 100
      1000 U/ml, for 24-48 h. Using RT-PCR and flow cytometry we showed that HKC
      express low levels of CD24 even under basal conditions, and the treatment with
      calcium, PMA or IFN-gamma increased levels of CD24 mRNA and protein. To the best
      of our knowledge, this is the first report to measure CD24 expression and
      production by cultured HKC in basal conditions and after stimulation. Further
      studies are needed to determine biological and therapeutical relevance of these
      findings.

PMID- 9758415
TI  - Camptothecin induces differentiation, tissue transglutaminase and apoptosis in
      cultured keratinocytes.
AB  - Cultured normal human adult keratinocytes were exposed to (S)-(+)- camptothecin
      over the concentration range 10(-5) to 10(-10) M. The dose-dependent inhibition
      of growth was recorded using cell counting. The induction of terminal
      differentiation was demonstrated by the relative increase in squamous and
      cornified cells, and the concomitant decrease in small, proliferative cells, with
      an overall decrease in total cell numbers on going from 10(-10) to 10(-6) M
      concentration of the drug. The induction of apoptosis was studied by assay of two
      types of transglutaminase, "tissue" and "keratinocyte", and by assay of histone
      linked mono- and oligonucleosomes. Induction of apoptosis was accompanied with
      increase in "tissue" transglutaminase and in the amount of nucleosomes, the
      latter being indicative of endonuclease activity. This activity was sharply
      increased at a camptothecin concentration of 10(-5) M, and may have been
      facilitated by "tissue" transglutaminase at lower concentrations. The data
      suggest that camptothecin restricts keratinocyte growth by several mechanisms
      including apoptosis and emphasize its possible use in topical therapy for
      psoriasis.

PMID- 9758416
TI  - Cell migration and MMP-9 secretion are increased by epidermal growth factor in
      HaCaT-ras transfected cells.
AB  - Mutated RAS oncoproteins and epidermal growth factor (EGF) are thought to
      contribute to the proliferative, invasive and metastatic properties of
      transformed cells. In the present study, we investigated the role of EGF in two H
      ras transfected clones and compared it to that in the parental cell line, HaCaT
      and primary cultured keratinocytes. Our findings show that the motility on type I
      collagen, measured by the migration index, was similar for both the HaCaT cell
      line and normal human keratinocytes, whereas it was higher for the HaCaT-ras
      clones. These results suggest an involvement of the ras oncogene in the
      stimulation of cell migration. EGF in cell pretreatment or during the migration
      assay also caused an increase in migration of all the cells, but preserved the
      difference between HaCaT and HaCaT-ras. However, no significant difference in EGF
      R expression was detected between normal cultured keratinocytes, HaCaT and HaCaT
      ras cell lines with or without EGF pretreatment. Moreover, when the cells were
      stimulated with EGF, the MMP-9 activity was greatly increased in a dose-dependent
      manner in all the cells, and EGF stimulation particularly highlights the
      increased amount of MMP-9 in HaCaT-ras cells compared to HaCaT cells. In
      conclusion, EGF is able to enhance motility and to up-regulate MMP-9 activity in
      all cells, but with a higher impact in HaCaT-ras cells without an overexpression
      of EGF-R. As EGF acts in synergy with the H-ras mutation, they could be
      implicated in the local invasion by the HaCaT-ras clones.

PMID- 9758417
TI  - Immunohistochemical investigation of evolving inflammation in lesions of acne
      vulgaris.
AB  - The mechanisms involved in the development of inflammation in acne vulgaris have
      yet to be elucidated. Previous studies have shown that the initial cellular
      infiltrate in early inflammatory lesions is mononuclear, predominantly CD4
      positive T cells. The aims of this study were to investigate the pattern of
      expression of adhesion molecules and HLA-DR in evolving acne lesions. Forty-nine
      patients with moderate to severe acne were biopsied following lesion mapping.
      Lesions were classified according to their duration of inflammation as up to 6 h,
      from 6 to 24 h, from 24 to 48 h and from 48 to 72 h. The cellular infiltrate was
      determined using monoclonal antibodies to CDI, CD3, CD4 and CD8. The expression
      of ICAM-1, E-selectin. VCAM-1 and HLA-DR was determined. Early (6 h) lesions had
      perivascular CD3 positive T-cell infiltrates which were predominantly CD4
      positive. This was associated with vascular expression of ICAM-1, E-selectin,
      VCAM-1 and HLA-DR. Periductal infiltrates were present in 70% of the early
      lesions (up to 6 h). The cells were predominantly CD4 positive and associated
      with a high level of HLA-DR and ICAM-1 expression. Periductal infiltration
      increased with time and persisted to 72 h. ICAM-1 and HLA-DR were expressed
      epidermally in early and late lesions. CD1 positive cells were a minor, but
      consistent element in the perivascular and periductal infiltrates of early and
      late lesions. There was no statistically significant difference in the levels of
      expression of E-selectin, VCAM-1, ICAM-1 or HLA-DR for lesions of different
      duration. The pattern of HLA-DR and adhesion molecule expression plus the nature
      of the cellular infiltrate supports the hypothesis that inflammation in acne is
      mediated by CD4 positive T cells.

PMID- 9758418
TI  - Human tyrosinase related protein-1 (TRP-1) does not function as a DHICA oxidase
      activity in contrast to murine TRP-1.
AB  - Tyrosinase related protein-1 is a melanocyte specific protein and a member of the
      tyrosinase gene family which also includes tyrosinase and TRP 2 (DOPAchrome
      tautomerase). In murine melanocytes, TRP-1 functions as a 5,6-dihydroxyindole-2
      carboxylic acid [DHICA] oxidase during the biosynthetic conversion of tyrosine to
      eumelanin and mutations affecting TRP-1 result in the synthesis of brown rather
      than black pelage coloration. In this study, we examined the putative DHICA
      oxidase activity of TRP-1 in human melanocytes using several approaches. We first
      utilized a line of cultured melanocytes established from a patient with a form of
      oculocutaneous albinism completely lacking expression of TRP-1 (OCA3). This line
      of melanocytes endogenously exhibited the same amount of DHICA oxidase activity
      as control melanocytes expressing TRP-1. In other experiments, cultured human
      fibroblasts were transfected with a cDNA for TRP-1, in either the sense or
      antisense direction, or with the retroviral vector alone. TRP-1 expression was
      induced in fibroblasts transfected with the TRP-1 cDNA in the sense direction
      only. Although TRP-1 was expressed by sense-transfected cells, there was no
      significant DHICA oxidase activity above controls. These results demonstrate that
      human TRP-1 does not use DHICA as a substrate for oxidation.

PMID- 9758419
TI  - Increased sensitivity to peroxidizing agents is correlated with an imbalance of
      antioxidants in normal melanocytes from melanoma patients.
AB  - We have previously shown an imbalance of the antioxidant system in some cultures
      of normal melanocytes from patients with melanoma. In order to evaluate if the
      alteration of the antioxidants could be the basis of an increased sensitivity to
      exposure to peroxidative agents, in cultured melanocytes from normal individuals
      (n = 11) and from patients with melanoma (n = 11), superoxide dismutase and
      catalase activities were evaluated by spectrophotometer, and the levels of
      vitamin E and of the polyunsaturated fatty acid of cell membranes were determined
      by gas chromatography mass spectrometry. In 5 out of the 11 cultures of
      melanocytes from melanoma patients, with respect to those from normal
      individuals, a significant decrease of catalase activity (Cat) associated with an
      increase of vitamin E (Vit E) concentration was found, whereas no significant
      modification of superoxide dismutase activity (SOD) was observed. A wide range of
      variability was detected in the percentage of the polyunsaturated fatty acids of
      the cell membranes and a correlation was found between the ratio SOD/Cat and the
      percentage of linoleic acid, indicating that the imbalance of the enzymatic
      antioxidants leads to a lipoperoxidative process. The electron microscopic
      examination of these cultures revealed many microvilli in the plasma membranes
      and nuclear infoldings and in the cytoplasm light vacuoles. Moreover some cells
      contained several dense bodies with a round shape and numerous spherical lamellae
      possibly representing immature melanosomes. Treatment with cumene hydroperoxide
      between 0.66 and 20 microM did not produce a significant modification of cell
      viability in melanocytes from normal individuals. On the contrary in melanocytes
      from melanoma patients correlated with the ratio Vit E/Cat, considered as a
      parameter of the antioxidant imbalance, a stimulatory effect was observed at 0.66
      microM CUH and a cytotoxic effect at 20 microM. In conclusion our results suggest
      that a constitutional alteration of the scavenger system could be present in
      normal melanocytes from melanoma patients and that this could be the basis for an
      increased sensitivity to pro-oxidant agents.

PMID- 9758420
TI  - Identification of beta-endorphin, alpha-MSH and ACTH peptides in cultured human
      melanocytes, melanoma and squamous cell carcinoma cells by RP-HPLC.

PMID- 9758421
TI  - Risk revisited.
AB  - As our knowledge of dental caries and periodontal diseases has increased, our
      perspective has changed from viewing these diseases as ubiquitous to one which
      sees a variety of risk profiles in a population. Now, from a perspective of
      assigning risk, caries and periodontitis can be thought to be more like some of
      our common medical conditions, i.e., certain people or subgroups of the
      population are at higher risk than others and that prevention and intervention
      involve a combination of personal behaviors and professional practices. Research
      into risk assessment, however, is often hampered by confusing and ambiguous use
      of terminology. This commentary proposes some specific definitions for terms used
      in risk assessment in dentistry. These terms include risk factor, risk indicator,
      demographic risk factor, risk predictor (risk marker), prognostic factor, risk
      model, and prediction model.

PMID- 9758422
TI  - Factors associated with adult periodontitis in a dental teaching clinic
      population.
AB  - Exposure to a number of environmental, behavioral and sociodemographic variables
      has been associated with increased prevalence and severity of adult
      periodontitis. However, it is not possible easily to identify the individuals
      most susceptible to this chronic disease. A case control study was conducted
      among a population of adults to determine what factors were associated with
      increased prevalence of moderate to advanced periodontitis. Clinical and
      radiographic data were obtained from dental charts and structured interviews were
      conducted by telephone to collect sociodemographic and behavioral data.
      Statistical modeling was completed for the total study population (35-87-year
      olds) and for two age-stratified subpopulations. Significant crude disease
      associations were observed between periodontitis and numerous explanatory
      variables. However, after adjustment for age and gender, few variables remained
      significant. Age stratification indicated that young adults (35-54 years) were
      affected differently from older adults (> or =55 years) by exposures to certain
      variables. Young moderate smokers had a 3.15 times increased risk of
      periodontitis and young heavy smokers had a 7.33 times increased risk compared to
      never-smokers. Older single adults had a 3.07 times increased risk compared to
      those with partners.

PMID- 9758423
TI  - Evaluation for an observation effect in a prospective cohort study of oral health
      outcomes.
AB  - OBJECTIVES: Evaluation for changes in behavior due to research participants'
      knowledge that behavior is being observed (also referred to as a Hawthorne effect
      or reactivity) has received little attention in the dental literature. The
      Florida Dental Care Study, a prospective, non-randomized, longitudinal study of
      oral health outcomes, provides some inferential power to evaluate for an effect
      on dental care use due to participants' knowledge that this behavior was being
      observed. The purpose of this paper is to document that an observation effect can
      occur in dental studies, and to estimate its magnitude in four groups that were
      defined by their typical approach to dental care as stated at baseline:
      consistent regular attenders (CRAs); inconsistent regular attenders (IRAs);
      consistent problem-oriented attenders (CPOAs); and inconsistent problem-oriented
      attenders (IPOAs). METHODS: At baseline, 873 respondents with at least one
      natural tooth and who were 45 years of age or older participated for an interview
      and clinical dental examination. Respondents were asked about their dental care
      use in general and check-up use in particular at 6-month intervals over a period
      of 24 months. RESULTS: Dental care use in general and check-up use in particular
      varied across time points and across the four groups of the sample. There was
      some stimulation in dental care use for the sample overall, but by the 18-to-24
      month period, use had returned to baseline levels. In a direction opposite from
      that hypothesized, results from the CRAs suggested decreased use of dental care
      over the course of the 24 months of observation. No consistent pattern was
      evident for the IRAs, CPOAs, or IPOAs. CONCLUSIONS: An observation effect was
      evident, but was modest in magnitude and differed within and between sub-groups
      of the sample. While self-selection into dental care user groups is an expected
      and desirable feature of this design, the size of the user/non-user groups was
      affected for some subgroups. We conclude that dental care studies with the
      potential for an observation effect should evaluate for this effect by
      distinguishing sub-groups of the sample based on their propensity (as stated at
      baseline) to use dental care. These differential effects across sub-groups should
      be taken into account as inferences are made.

PMID- 9758424
TI  - Fluorosis risk from early exposure to fluoride toothpaste.
AB  - Swallowed fluoride toothpaste in the early years of life has been postulated to
      be a risk factor for fluorosis, but the epidemiological evidence is weakened by
      the fact that most of the relevant studies were done in developed countries where
      an individual is exposed to multiple sources of fluoride. OBJECTIVES: To quantify
      the risk of fluorosis from fluoride toothpaste in a population whose only
      potential source of fluoride was fluoride toothpaste. METHODS: Case-control
      analyses were conducted to test the hypothesis that fluoride toothpaste use
      before the age of 6 years increased an individual's risk of fluorosis. Data came
      from a cross-sectional clinical dental examination of schoolchildren and a self
      administered questionnaire to their parents. The study was conducted in Goa,
      India. The study group consisted of 1189 seventh grade children with a mean age
      of 12.2 years. RESULTS: The prevalence of fluorosis was 12.9% using the TF index.
      Results of the crude, stratified, and logistic regression analyses showed that
      use of fluoride toothpaste before the age of 6 years was a risk indicator for
      fluorosis (OR 1.83, 95% CI 1.05-3.15). Among children with fluorosis, beginning
      brushing before the age of 2 years increased the severity of fluorosis
      significantly (P<0.001). Other factors associated with the use of fluoride
      toothpaste, such as eating or swallowing fluoride toothpaste and higher frequency
      of use, did not show a statistically significant increased risk for prevalence or
      severity of fluorosis. CONCLUSIONS: Fluoride toothpaste use before the age of 6
      years is a risk indicator for fluorosis in this study population.

PMID- 9758425
TI  - Estimation of optimal concentration of fluoride in drinking water under
      conditions prevailing in Chile.
AB  - The purpose of this comparative study of caries and dental fluorosis experience
      in Chilean children was to estimate the optimal range of fluoride concentration
      in tap water under conditions currently prevailing in Chile. The sample included
      2431 schoolchildren 7, 12 and 15 years old, life-long residents of five
      communities with fluoride concentrations in their tap water in the range 0.07-1.1
      mg/L. The study population received an oral clinical examination including caries
      experience and an enamel fluorosis evaluation of the permanent dentition (Dean's
      scoring system). For 15-year-old children, the DMFT index changed from 5.06 to
      2.60, and for 12-year-olds it changed from 3.10 to 1.36 when fluoride water
      concentration changed from 0.07 to 1.10 mg/L. For 7-year-old children the dmft
      index correspondingly changed from 3.67 to 1.59. The relationship between DMFT
      for 12-year-olds and water fluoride concentration was best fitted by a
      logarithmic function (r2=0.98). The Community Fluorosis Index (CFI) was used to
      assess enamel fluorosis in the study population, and it showed a linear
      relationship (r2=0.983) with increasing fluoride concentration of water for the
      12-year-old group. Results obtained suggest that under current Chilean
      conditions, the optimal range of fluoride concentration in potable water should
      lie in the 0.5-0.6 mg/L range.

PMID- 9758426
TI  - Caries frequency in permanent teeth before and after discontinuation of water
      fluoridation in Kuopio, Finland.
AB  - The piped water of Kuopio, Finland, was fluoridated in 1959. Owing to strong
      opposition by different civic groups, water fluoridation was stopped at the end
      of 1992. OBJECTIVES: The aim of this study was to examine the consequences of the
      discontinuation on dental health. METHODS: In 1992 and 1995, independent random
      samples of all children aged 6, 9, 12 and 15 years were drawn from Kuopio and
      Jyvaskyla, a nearby low fluoride town whose distribution of demographic and socio
      economic characteristics was fairly similar to Kuopio's. The total number of
      subjects examined was 550 in 1992 and 1198 in 1995. Caries was registered
      clinically and radiographically by the same two calibrated dentists in both
      towns. RESULTS: In 1992, the mean DMFS values were lower in the fluoridated town
      for the two older age groups, the percentage differences for 12- and 15-year-olds
      being 37% and 29%, respectively. For the two younger age groups no meaningful
      differences could be found. In 1995, the only difference with possible clinical
      significance was found in the 15-year-olds in favor of the fluoridated town
      (18%). In 1995, a decline in caries was seen in the two older age groups in the
      nonfluoridated town. In spite of discontinued water fluoridation, no indication
      of an increasing trend of caries could be found in Kuopio. The mean numbers of
      fluoride varnish and sealant applications decreased sharply in both towns between
      1992 and 1995. In spite of that caries declined. CONCLUSIONS: These findings
      suggest that the decline of caries has little to do with professional preventive
      measures performed in dental clinics.

PMID- 9758427
TI  - Caries preventive services for children and adolescents in Denmark, Iceland,
      Norway and Sweden: strategies and resource allocation.
AB  - According to the dental acts of Denmark, Iceland, Norway and Sweden, emphasis is
      placed on preventive dental care. The purpose of this study was to describe and
      compare two aspects of the caries preventive services: the strategies and the
      resource allocation for preventive dental care of children and adolescents in
      Denmark, Iceland, Norway and Sweden. Questionnaires were sent to samples of
      dentists and other dental personnel who provided preventive care to children
      during 1995 and 1996. Comparisons between the countries showed significant
      differences in recall routines and in implementation of risk-based and population
      based preventive strategies. Multivariate analyses showed that the time used for
      preventive care varied by country and was not associated with the DMFT of the
      children. More time was allocated for prevention when more operating dental
      auxiliaries were available at the clinic, when the recall interval was shorter,
      when the time used for routine examination was longer and when the clinician was
      an auxiliary rather than a dentist. In conclusion, resource allocation and
      strategies used for prevention were not consistent between the countries.

PMID- 9758429
TI  - Cost and productivity analysis of orthodontic care in Finland.
AB  - The aim of the study was to investigate the costs of orthodontic care provided
      for children and adolescents up to the age of 18 by municipal health centers in
      Finland, and to study the productivity of these services. The data were gathered
      by a questionnaire sent to all health centers; 96% responded. The majority of
      respondents estimated the share of orthodontic care as 10% of the total gross
      costs of dental care, given that 14% of all dental visits were for orthodontic
      reasons. To study the productivity in individual health centers, the output was
      measured by the estimated number of completely treated patients. The cost of
      orthodontic treatment per completely treated patient was, on average, FIM 7358,
      ranging from FIM 1299 to FIM 24751. The strongest explanatory factor for the
      average total costs of orthodontic clinics was the number of general dentists
      with little experience in providing orthodontic treatment. Other explanatory
      factors were the number of orthodontists or experienced dentists, the percentage
      of orthodontic tasks performed by auxiliary personnel, and the timing of
      treatment. Savings might be obtained by devolving treatment to orthodontists or
      experienced dentists instead of to dentists with little orthodontic experience,
      and by starting treatment early. The estimated optimal size for an orthodontic
      clinic was found to be a unit with 830 completely treated patients per year, but
      most of the orthodontic clinics were in fact much smaller with, on average, 133
      completely treated patients per year.

PMID- 9758428
TI  - Evaluation of a dental benefit plan for children conducted in Auvergne, France,
      since 1992.
AB  - Usually, the French dental insurance system covers the cost of restorative
      treatment but does not reimburse the cost of preventive therapies. A French sick
      fund covering self-employed persons tested a new dental benefit plan for children
      intended to provide an incentive to develop office-based preventive activities.
      The programme, which started in 1992, concerns all 4-year-old children of self
      employed workers in a single French region (Auvergne). Participants undergo an
      annual examination by the dentist of their choice until their 15th birthday. If
      the child is seen every year, all services related to dental caries (preventive
      and restorative) are provided free of charge. An ongoing evaluation of the
      programme was necessary to determine its influence on the development of office
      based preventive activities and the dental health of the participants. A cohort
      of children enrolled in the programme in 1992 was followed over 4 years to
      examine the patterns of service use. In addition, a cross-sectional study
      comparing the caries experience of all 8-year-old children participating
      continuously in the programme (test sample) with that of a sample of control
      children (n=90) was conducted in 1996. Data from the longitudinal follow-up
      indicate that 43.37% of the 551 children to whom the programme was offered in
      1992 underwent an annual examination in the first year. Of the children enrolled
      in 1992, 55.2% were still participating in the programme in 1996. Results showed
      that independent practitioners continued to focus on restorative treatment rather
      than preventive therapy. Results from the cross-sectional study are in accordance
      with this trend. The number of caries-free children was identical in test and
      control samples and the mean dft, DMFT, DT and dt did not vary between the two
      groups (Student's t-test, P>0.05). However the mean number of filled teeth was
      significantly higher in the test children than in the controls (P<0.01). For
      children with caries, the mean dft was 23.5% greater in the test group than in
      the control group (P<0.05). In Auvergne, a large number of families were not
      ready to participate in a plan that required them to take their child to the
      dentist every year. There was not a perceived need for regular preventive dental
      care, an attitude probably reinforced by the interventionist approach undertaken
      by the dentists over the survey period. Moreover, the plan did not provide an
      incentive for dentists to develop office-based preventive activities.

PMID- 9758430
TI  - Mitochondrial regulation of mineralocorticoid biosynthesis by calcium and the
      StAR protein.

PMID- 9758431
TI  - Delayed puberty and peak bone mass.

PMID- 9758432
TI  - Transcriptional repression: lessons from thyroid hormone action and promyelocytic
      leukaemia.

PMID- 9758433
TI  - Insulin receptor substrate-2--a new candidate gene for NIDDM?

PMID- 9758434
TI  - A biological function for glucagon-like peptide-2.

PMID- 9758435
TI  - Bone mineral status in prepubertal children with constitutional delay of growth
      and puberty.
AB  - OBJECTIVE: We wished to clarify whether the osteopenia reported in adult men with
      a history of constitutional delay of growth and puberty (CDGP) could be due to
      the delayed puberty or an independent predisposition to osteoporosis in this
      condition. DESIGN: Short prepubertal children with CDGP and children with
      familial short stature (FSS) were matched for height and other auxological
      variables. The FSS children served as a control group. METHODS: We measured
      spinal (L1-L4) bone mineral content (BMC) and bone mineral density (BMD) by dual
      energy X-ray absorptiometry (Hologic QDR 1000/w) in 56 children aged 5-11 years.
      All children had height below the 10th percentile for chronological age (CA), and
      bone age (BA) less than 10 years, 29 of them with clinical diagnosis of possible
      CDGP and 27 of them with FSS. The BMD standard deviation scores (SDS) relative to
      the values for normal height children were obtained. RESULTS: The mean (+/-S.D.)
      spinal BMD was significantly lower in the children with CDGP than in the FSS
      group (0.534+/-0.059 vs 0.623+/-0.060 g/cm2, P< 0.001). Both groups had negative
      mean lumbar BMD SDS, but in the CDGP group it was significantly lower than in the
      FSS group as well when the SDS was based on the CA (-1.41+/-0.61 vs -0.38+/-0.51,
      P< 0.001) and when it was related to BA (-0.78+/-0.64 vs -0.17+/-0.52, P< 0.01).
      BMC was significantly lower in the CDGP than in the FSS group, when multiple
      regression analysis was performed by using scanned bone area, body weight and
      height, sex and BA as independent variables (P = 0.0005). CONCLUSION: The finding
      of decreased mineralization in prepubertal children with CDGP before the age of
      puberty suggests that they may have an inherent predisposition to osteopenia.

PMID- 9758436
TI  - The importance of body weight history in the occurrence and recovery of
      osteoporosis in patients with anorexia nervosa: evaluation by dual X-ray
      absorptiometry and bone metabolic markers.
AB  - In order to investigate the risk factors, pathogenesis and natural course of the
      osteoporosis frequently seen in anorexia nervosa, we measured the bone mineral
      density (BMD) of the lumbar spine using dual X-ray absorptiometry in 51 Japanese
      female patients with anorexia nervosa, and followed the change in BMD of 29
      patients for 11 to 46 months. We also evaluated the serum osteocalcin and the
      urinary CrossLaps, degradation products of collagen I, in 103 samples obtained
      from 51 patients. There was a significant correlation between the spinal BMD and
      the duration of emaciation below a body mass index (BMI) of 15kg/m2 (r= -0.652,
      P<0.0001) and 16kg/m2 (r= -0.647, P<0.0001). The increase in BMD per year in the
      29 patients significantly correlated with the BMI at the time of entry of each
      follow-up period (r= 0. 712, P<0.0001). The critical BMI for a positive increase
      in BMD was 16.4+/-0.3 kg/m2 (mean+/-S.E.M.). The serum osteocalcin declined,
      while the urinary CrossLaps increased in proportion to a decrease in BMI. Both
      markers were normalized in patients whose BMI was between 16.4 and 18.5 kg/m2.
      The ratio of urinary CrossLaps to serum osteocalcin correlated with BMI (r= 
      0.664, P<0.0001). We conclude that the body weight history is the most important
      predictor of the presence of osteoporosis as well as of recovery The BMD of
      patients does not increase to the normal range even several years after the
      recovery from this disorder, and they remain a high-risk group for osteoporosis
      in the future.

PMID- 9758437
TI  - Management of hypoparathyroidism during pregnancy--report of twelve cases.
AB  - There is no established therapeutic regimen for treatment of hypoparathyroidism
      during pregnancy. This is due particularly to uncertainty about the use of
      vitamin D or its analogues, as in animal experiments teratogenic side-effects
      have been reported. Nevertheless, vitamin D or its analogues are required to
      control tetany predisposing to abortion and preterm labour. We herein report the
      course of two pregnancies in a hypoparathyroid woman treated with calcitriol
      (1,25(OH)2D3). Additionally, we describe the outcome of pregnancy in ten women
      receiving calcitriol, reported to the Drug Safety Department (DSD), Hoffmann-La
      Roche AG. A 29-year-old hypoparathyroid woman receiving chronic treatment with
      calcitriol (0.25 microg/day) and calcium (1.5 g/day) was referred in the 6th week
      of her first pregnancy. Calcitriol was initially discontinued, but during the
      20th week of pregnancy recurrent tetany occurred (serum calcium 1.74 mmol/l).
      Calcitriol (0.25 microg/day) was added, stabilizing serum calcium around 2.15
      mmol/l with 1,25(OH)2D3 concentrations around 60 ng/l (normal range 35-80 ng/l).
      To maintain normocalcaemia the calcitriol dose was increased to 0.5 microg/day
      during the 33rd week and to 0.75 microg/day shortly before delivery of a healthy
      girl in the 3 7th week. During her second pregnancy calcitriol was given
      initially at a dose of 0.25 microg/day with further adaptation to 0.5 microg/day
      during the 20th and to 1.00 microg/day in the 31st week. Serum calcium and
      1,25(OH)2D3 were continually within the lower normal range. She gave birth to
      another healthy girl during the 39th week. In eight of the ten pregnancies
      reported to the DSD no adverse effects of calcitriol (0.25-3.25 microg/day) were
      seen and healthy babies were delivered. In two retrospectively reported cases,
      serious adverse events were described: premature closure of the frontal
      fontanelle, and stillbirth in the 20th week due to complex fetal malformation
      respectively. However, in both cases the causative role of calcitriol
      administration remains highly questionable. We conclude that, during pregnancy,
      management of maternal hypoparathyroidism with calcitriol and calcium is
      feasible, if the 1,25(OH)2D3 concentrations are adapted to the physiological
      needs during pregnancy and serum calcium levels are kept in the lower normal
      range.

PMID- 9758438
TI  - Iodide induces thyroid autoimmunity in patients with endemic goitre: a
      randomised, double-blind, placebo-controlled trial.
AB  - OBJECTIVE: Iodine is essential for normal thyroid function and the majority of
      individuals tolerate a wide range of dietary levels. However, a subset of
      individuals, on exposure to iodine, develop thyroid dysfunction. In this double
      blind trial, we evaluated the efficacy and tolerability of low-dose iodine
      compared with those of levo-thyroxine (T4) in patients with endemic goitre.
      METHODS: Sixty-two patients were assigned randomly to groups to receive iodine
      (0.5 mg/day) or T4 (0.125 mg/day) for 6 months. Subsequently, both groups were
      subject to placebo for another 6 months. Thyroid sonography, determination of
      thyroid-related hormones and antibodies, and urinary excretion of iodine were
      carried out at baseline and at 1, 6 and 12 months. RESULTS: At 6 months, markedly
      increased urinary values of iodine were found in patients receiving iodine (36
      microg/24 h at baseline, 415 microg/24 h at 6 months) compared with those
      receiving T4 (47 microg/ 24 h at baseline, 165 microg/24 h at 6 months; P <
      0.0001 compared with iodine group). T4 administration engendered a greater (P <
      0.01) decrease in thyroid volume (from 32 ml to 17 ml, P < 0.0001) than did
      intake of iodine (3 3 ml to 21 ml. P < 0.005). High microsomal and thyroglobulin
      autoantibody titres were present in six of 31 patients (19%) receiving iodine,
      and iodine-induced hypo- and hyperthyroidism developed in four and two of them,
      respectively. Fine-needle biopsy revealed marked lymphocyte infiltration in all
      six. After withdrawal of iodine thyroid dysfunction remitted spontaneously and
      antibody titres and lymphocyte infiltration decreased markedly. Follow-up of
      these six patients for an additional 3 years showed normalisation of antibody
      titres in four of them. CONCLUSION: Although nearly comparable results were
      obtained with both treatment regimens regarding thyroid size, partly reversible
      iodine-induced thyroid dysfunction and autoimmunity were observed among patients
      with endemic goitre.

PMID- 9758439
TI  - Pulsatile GnRH or human chorionic gonadotropin/human menopausal gonadotropin as
      effective treatment for men with hypogonadotropic hypogonadism: a review of 42
      cases.
AB  - Stimulatory therapy with either GnRH or gonadotropins is an effective treatment
      to induce spermatogenesis and achieve paternity in men with secondary
      hypogonadism. However, there is still uncertainty about the optimal treatment
      modality and schedule, the duration of treatment necessary and the influence of
      interfering factors such as maldescended testes. We have extended our previous
      series of men treated for secondary hypogonadism and now present our therapeutic
      experience with 42 cases. Twenty-one patients with hypothalamic disorders (11
      with idiopathic hypogonadotropic hypogonadism (IHH) and 10 with Kallmann syndrome
      (KalS)) were treated with GnRH (group Ia) or human chorionic gonadotropin
      (hCG)/human menopausal gonadotropin (hMG) (group Ib), and 21 patients with
      hypopituitarism (group II) were treated with hCG/hMG. A total of 5 7 treatment
      courses were initiated for induction of spermatogenesis, 36 of these for the
      purpose of induction of pregnancy in the female partner. Bilateral testicular
      volumes doubled within 5-12 months of therapy. Spermatogenesis as evidenced by
      the appearance of sperm in the ejaculate was induced in 54/57 courses.
      Pregnancies occurred in 26/36 courses. Unilaterally maldescended testes did not
      preclude patients with IHH or KalS from gaining fertility under therapy and
      spermatogenesis could be successfully initiated even in some individuals with
      bilateral maldescended testes. In general there was a tendency for a longer
      duration of therapy until induction of spermatogenesis in patients with a history
      of bilateral cryptorchidism. However, this did not reach statistical
      significance. In patients with IHH or KalS treated with either hCG/hMG or GnRH
      there were no statistically significant differences in terms of duration to
      appearance of sperm or pregnancy rates. Even in KalS patients as old as 43 years
      spermatogenesis could be induced. In repeatedly treated patients stimulation of
      spermatogenesis tended to be faster while time until induction of pregnancy was
      significantly shorter in the second treatment course. In conclusion, GnRH or
      hCG/hMG are effective therapeutic modalities for patients with IHH or KalS. It
      remains to be determined whether highly purified urinary gonadotropin
      preparations or recombinant LH and FSH will provide therapeutic advantages.

PMID- 9758440
TI  - High serum luteinizing hormone levels induce ovarian delta4 cytochrome
      P450c17alpha down-regulation in hirsute women: complete effect on 17-hydroxylase
      and partial effect on 17,20-lyase.
AB  - It is well known that normal and mildly elevated luteinizing hormone (LH) levels
      induce increased activity of ovarian 17-hydroxylase and 17,20-lyase, the
      cytochrome P450cl7alpha (P450) enzymes. This leads to increased ovarian 17alpha
      hydroxyprogesterone (17-OHP) and androstenedione production. In contrast, it has
      been shown in both in vitro and in vivo studies in animals and in in vitro
      studies in women that high LH concentrations have opposite effects on these
      enzymes. These LH down-regulating effects appear to be more marked on 17,20-lyase
      than on 17-hydroxylase. Finally, these LH effects have not been reported in vivo
      in women. Therefore, we investigated the relationships between serum LH levels
      and serum 17-OHP and androstenedione concentrations in 263 consecutive hirsute
      women (HW) with normal serum 17-OHP responses to acute adrenocorticotropin (ACTH)
      stimulation. The patterns of basal serum steroid concentrations differed
      according to the basal serum LH levels. Indeed, for relationships between LH and
      17-OHP concentrations, a positive correlation (P < 0.001) was found between the
      levels of these parameters when LH levels ranged from 0.2 to 9.0 IU/l.
      Conversely, for LH levels greater than 9.0 to 21.0 IU/l, LH values were
      negatively correlated (P<0.001) with 17-OHP concentrations. Similar results were
      observed for relationships between LH and androstenedione levels but the LH peak
      level related to decreasing androstenedione concentrations was 12.0 IU/l.
      Finally, the mean 17-OHP level in patients with LH levels which induced marked
      P450 down-regulation (i.e. more than 12 IU/l) was similar to that in patients
      with LH levels within the normal range (i.e. less than 6 IU/l). In contrast, the
      mean androstenedione level in the former patients was markedly higher (P<0.001)
      than that in the latter patients. In conclusion, as previously reported in in
      vitro studies, this in vivo study indicates that LH induces stimulating and down
      regulating effects on both ovarian delta(4)17-hydroxylase and delta(4)17,20-lyase
      activities as serum LH levels gradually increase. However, in contrast to in
      vitro studies, LH levels which induce P450 down-regulation appear to be less
      effective on delta(4)17,20-lyase than on delta(4)17-hydroxylase in HW. This
      strongly suggests that serum factors induce, in most HW, a marked increase in
      delta(4)17,20-lyase, but not in delta(4)17-hydroxylase, activity leading to both
      partial impairment of LH-induced delta(4)17,20-lyase down-regulation and complete
      LH-induced delta(4)17-hydroxylase down-regulation in these patients.

PMID- 9758442
TI  - Serial analysis of the effects of methimazole or radical therapy on circulating
      CD16/56 subpopulations in Graves' disease.
AB  - The distribution of peripheral blood CD16/56 cytotoxic T and natural killer (NK)
      cells in Graves' disease patients is analyzed in order to correlate them with
      disease activity and with prognosis. Eighteen patients with Graves' disease,
      twenty-four patients with Hashimoto's thyroiditis and thirty-two sex- and age
      matched healthy control subjects were studied. Peripheral blood CD16/56
      (cytotoxic T and NK) cells were analyzed by cytofluorometry. A decreased
      proportion of CD16/56+ and CD16/ 56+CD3+ cells were detected in Graves' disease
      patients when compared with thyroiditis patients and healthy control groups. No
      correlation was detected with serum free thyroxine. On diagnosis, patients who
      would require a radical treatment for thyrotoxicosis control showed a significant
      decrease of cytotoxic CD56+ T (CD3+) and NK (CD3-) cells compared with those who
      would maintain the euthyroid state after methimazole. These results suggest that
      the cytotoxic compartment, both T and NK cells, of the immune system is altered
      in patients with Graves' disease, independently of the functional thyroid status.
      Changes in peripheral blood lymphocytes in Graves' disease patients could be
      useful as predictive markers of an unfavorable outcome.

PMID- 9758443
TI  - Study of serum big-insulin-like growth factor (IGF)-II and IGF binding proteins
      in two patients with extrapancreatic tumor hypoglycemia, using a combination of
      Western blotting methods.
AB  - Extrapancreatic tumor hypoglycemia (EPTH) is associated with increased amounts of
      high-molecular-weight precursor forms of insulin-like growth factor (IGF)-II
      ('big-IGF-II') that have a primary role in the pathophysiology of hypoglycemia.
      In the present study, using Western ligand and immunoblotting methods, we
      investigated IGF-binding proteins (IGFBPs), IGFBP-3 proteolysis and big-IGF-II in
      pre- and postoperative serum from two patients with EPTH due to benign pleural
      fibroma. In the preoperative serum, IGFBP-3 was reduced and IGFBP-2 was increased
      compared with that from an age-matched healthy control. IGFBP-3 proteolysis was
      dramatically reduced in one patient, whereas no major alteration was observed in
      the other (9% and 120% of control serum, respectively). IGFBPs progressively
      returned to a subnormal pattern in postoperative serum, whereas IGFBP- 3
      proteolysis remained greater than in preoperative serum in both patients at days
      14 and 90 after surgery. High-molecular-weight forms of IGF-II predominate in
      EPTH serum (65% and 57% of total IGF-II immunoreactivity in patients 1 and 2,
      respectively, compared with 2 5% in control serum). Two forms, of molecular mass
      10 and 12 kDa ('standard big-IGF-II') were present in both EPTH and control sera,
      whereas two additional forms, of molecular mass 15 and 18 kDa ('big big-IGF-II')
      were observed in EPTH sera only. Big big-IGF-II represented 72% and 55% of total
      high-molecular-weight forms of IGF-II in the two EPTH sera, respectively. All big
      forms of IGF-II disappeared from the serum as early as 6 h after surgery. This
      study shows that combination of simple Western blotting methods, available
      routinely in most laboratories, should prove useful in providing reliable
      physiopathological information in EPTH.

PMID- 9758441
TI  - Effect of acute and chronic administration of tamoxifen on GH response to GHRH
      and on IGF-I serum levels in women with breast cancer.
AB  - Tamoxifen, an estrogen antagonist, is usually employed in the treatment of breast
      cancer. Its mechanism of action is not well known because an antiproliferative
      effect of the drug has been shown also in estrogen receptor negative tumors, most
      likely mediated by the inhibition of local growth factors and particularly IGF-I.
      However, the action of tamoxifen on the GH-IGF-I axis is still open to
      investigation. We have investigated the influence of acute and chronic treatment
      with tamoxifen on GH response to GHRH and IGF-I serum levels in six
      postmenopausal women with metastatic breast cancer. A GHRH test (50 microg i.v.
      at time 0, GH determinations at 0, 15, 30, 60, 90 and 120 min) was performed (a)
      basally, (b) 3 h after 40 mg oral administration of tamoxifen and (c) after 8
      weeks of 20 mg twice a day oral tamoxifen treatment. IGF-I was measured basally
      and after chronic tamoxifen therapy. No significant modifications in GH response
      to GHRH were observed after acute or chronic treatment with tamoxifen vs the
      basal test. On the contrary, chronic tamoxifen treatment induced a significant
      decrease in serum IGF-I levels. Basal pretreatment levels of 123+/-18 microg/l
      were suppressed to 65+/-11 microg/l (mean suppression 47%, P < 0.001). These
      preliminary data confirm the inhibitory effect of tamoxifen on IGF-I production
      but seem to exclude the possibility that this effect may be due to an inhibition
      of GH secretion.

PMID- 9758444
TI  - Utility of measuring serum parathyroid hormone-related protein concentration in
      leukemic patients with hypercalcemia for assessing disease status.
AB  - OBJECTIVE: To evaluate serum parathyroid hormone-related protein (PTHrP) as a
      marker of hypercalcemia in leukemic patients. DESIGN AND METHODS: We measured the
      serum levels of PTHrP, lactate dehydrogenase (LDH) and calcium in three patients
      with hypercalcemia due to leukemia. RESULTS: Serum levels of PTHrP, LDH and
      calcium were elevated at admission in all patients, and these levels were reduced
      to within the normal range after chemotherapy. However, normalization of serum
      PTHrP concentration occurred more rapidly than normalization of serum LDH levels
      after chemotherapy. The increase in serum PTHrP concentration accompanied
      leukemic cell proliferation and preceded the increases in serum LDH and calcium.
      Serum LDH concentration increased, but serum PTHrP concentration did not after
      administration of granulocyte colony-stimulating factor. CONCLUSION: These
      findings suggest that serum PTHrP may be a more useful marker than serum LDH or
      calcium in assessing the status of leukemic patients with hypercalcemia.

PMID- 9758446
TI  - Prolactin secretion and its dopamine inhibitory control in rat fetuses.
AB  - This study has determined in rats the ontogenetic schedule of the onset of
      pituitary prolactin (PRL) synthesis and release as well as of the establishment
      of the dopamine (DA) inhibitory control of PRL secretion. RIA recognized PRL
      traces in the pituitary at the 18th embryonic day (E18), although a clearly
      detectable amount of this hormone was first measured at E20, suggesting the onset
      of PRL synthesis. The PRL level in the pituitary increased significantly by E22,
      in females to a higher extent than in males. Decapitation of fetuses did not
      cause any change in the PRL plasma level in males showing no PRL release from the
      pituitary until term. Conversely, there was a slight but significant fall of
      plasma PRL in decapitated females, suggesting PRL release from the pituitary. An
      inhibition of DA receptors on lactotropes of fetuses resulted in an increased
      level of plasma PRL at E20, but not at E18, while the pituitary content of PRL
      remained unchanged. The same treatment at E22 caused a significant increase of
      the PRL concentration in plasma and a concomitant fall in the pituitary that
      could be prevented by preliminary encephalectomy. These data show that the
      tuberoinfundibular DA system begins to inhibit PRL release from lactotropes
      between E20 and E22, completely arresting PRL release from the pituitary in males
      but not in females.

PMID- 9758445
TI  - A novel missense (R80W) mutation in 17-beta-hydroxysteroid dehydrogenase type 3
      gene associated with male pseudohermaphroditism.
AB  - OBJECTIVE: Deficit of the testosterone converting enzyme 17-beta-hydroxysteroid
      dehydrogenase (17beta-HSD) has been shown to be responsible for male
      pseudohermaphroditism (MPH). We analysed the gene encoding 17beta-HSD type 3
      (17beta-HSD3) in a patient with MPH. METHODS: We studied a 46, XY new-born
      diagnosed as having MPH. The child also had other congenital disorders, including
      a giant omphalocele and Fallot's tetralogy, and died of post-surgical
      complications at age 4.5 months. Basal hormonal levels, and after human chorionic
      gonadotrophin stimulation, suggested a deficiency in 17beta-HSD as the
      biochemical defect underlying this MPH. PCR amplification and subsequent
      sequencing of all coding exons of the 17beta-HSD3 gene were performed on genomic
      DNA from the patient and both parents. Messenger RNA was extracted from the
      patient's testis and 17beta-HSD3 cDNA was synthesized, PCR amplified and
      sequenced. RESULTS: Sequencing revealed the presence of a homozygous missense
      mutation (R80W) in exon 3 of the 17beta-HSD3 gene, which was also present in
      single doses in both parents, in accordance with the recessive inheritance of the
      defect. No other mutation was found, and cDNA sequencing confirmed correct
      synthesis and processing of 17beta-HSD3 mRNA. CONCLUSIONS: Confirming the
      abnormal delta4-androstenedione/testosterone ratios that suggested 17beta-HSD
      deficiency, a homozygous missense mutation in the gene coding for this enzyme was
      identified in the patient with MPH. This study adds further genetic evidence to
      the role of 17beta-HSD3 in male sexual development. There is no evidence
      supporting the association of this mutation in 17beta-HSD3 with the congenital
      malformations other than MPH present in the child.

PMID- 9758447
TI  - Growth hormone-releasing hexapeptide (GHRP-6) increases intracellular calcium
      concentrations in cultured cells from human pituitary adenomas of different
      types.
AB  - OBJECTIVE: The GH-releasing peptide GHRP-6, has been found to interact with
      specific receptors in somatotrophs, causing cytosolic Ca2+ ([Ca2+]i) rise and GH
      release. Moreover, this peptide has been demonstrated to stimulate the secretion
      of pituitary hormones other than GH, i.e. ACTH and prolactin, this effect being
      generally attributed to a central action. In this study we evaluated whether the
      pituitary action of this peptide is restricted to cell type of somatotroph
      lineage. METHODS: The effect opf GHRP-6 on [Ca2+]i was tested in cell
      preparations obtained from a series of human pituitary adenomas (9 GH-secreting
      adenomas, 7 nonfunctioning adenomas, 3 ACTH-secreting adenomas, 2 TSH-secreting
      adenomas and 1 prolactinoma) loaded with the Ca2+ indicator fura-2. RESULTS: GHRP
      6, at concentrations higher than 1 nmol/l, significantly increased [Ca2+]i in all
      tumours, with the exception of the 3 ACTH-secreting adenomas in which the peptide
      was ineffective at any concentration tested (from 1 nmol/l to 1 micromol/l). By
      contrast, in all ACTH-secreting adenomas, both corticotrophin-releasing hormone
      and pituitary adenylate cyclase activating peptide caused a marked [Ca2+]i
      increase. In tumours responsive to GHRP-6, the peptide caused a typical biphasic
      [Ca2+]i rise due to Ca2+ mobilization from the intracellular stores and Ca2+
      influx through voltage-dependent Ca2+ channels. CONCLUSIONS: These data indicate
      that almost all tumoral pituitary cell types are targets of GHRP-6 action, the
      only exception being corticotrophs.

PMID- 9758448
TI  - The expression of the beta 1 integrin CD29 and the beta 2 integrin CD11b is
      decreased in peripheral blood lymphocytes from Graves' disease patients.
AB  - We have prospectively examined the percentage of peripheral blood lymphocytes
      which expressed adhesion molecules in untreated Graves' disease patients.
      Eighteen patients with Graves' disease, twenty-four patients with Hashimoto's
      thyroiditis and thirty-two sex- and age-matched healthy control subjects were
      studied. The expression of the lymphocyte adhesion molecules beta-1 integrin
      CD29, beta-2 integrin CD11b and L-selectin Leu8 (CD62L) was analyzed by
      cytofluorometry. A decreased percentage of CD29+ and CD11b+ lymphocytes was
      observed in hyperthyroid patients in comparison with Hashimoto's thyroiditis
      patients and healthy controls. However, there was no difference in the percentage
      of CD62L+ lymphocytes in the three groups. Percentages of lymphocyte activation
      markers, hyperthyroid status, presence or absence of ophthalmopathy or serum
      levels of antithyroid antibodies were not related to the proportions of CD29+ or
      CD11b+ lymphocytes. Four Graves' patients required radical therapy but after the
      treatment, there was no modification in the percentages of CD29+ and CD11b+
      lymphocytes compared with those determined at diagnosis. Our findings suggest
      that the decrease in beta-1 and beta-2 integrins could be a predisposing marker
      of development of Graves' disease.

PMID- 9758450
TI  - When to refer.

PMID- 9758449
TI  - Heterogeneous signal pathways through TSH receptors in porcine thyroid cells
      following stimulation with Graves' immunoglobulin G.
AB  - OBJECTIVE: We compared different signal transduction pathways through thyroid
      stimulating hormone receptor (TSH-R) in porcine thyroid cells (PTC) following
      stimulation with thyroid stimulating hormone (TSH) and 11 thyroid stimulating
      immunoglobulin samples (TSI) obtained from patients with Graves' disease. DESIGN:
      Following stimulation with TSI, the level of inositol trisphosphate (IP3) and
      [Ca2+]i, as well as the membrane bound protein kinase C (PKC) activity and the
      intensity of the arachidonic acid (AA) cascade, were determined in PTC. RESULTS:
      Seven out of eleven TSI samples activated PTC through IP3 generation, elevated
      [Ca2+]i from the intracellular pools, exhibited verapamil-insensitive membrane
      bound PKC activation, and enhanced release of [14C]AA derivates (however, one of
      the samples was also able to take up Ca2+ from the extracellular space). Four out
      of eleven TSI samples did not activate the phospholipase C (PLC) system in which
      case the Ca2+ signal occurred only in the presence of extracellular Ca2+, the
      membrane bound PKC activation was verapamil sensitive, and in two of these four
      TSI samples, the AA release was extremely high. CONCLUSIONS: The simultaneous
      examination of the majority of the known signal pathways using TSI samples showed
      that TSI samples from different patients activate thyroid cells through different
      pathways. Their effects differ from that of TSH and, to a certain extent, from
      each other. The results give a certain new insight into the intracellular
      mechanisms exerted by TSI.

PMID- 9758451
TI  - The pediatric Monteggia fracture.
AB  - Since Monteggia first described the fracture bearing his name in 1814, the
      association of radial head dislocation with ipsilateral ulnar fracture has been
      well described. Monteggia fractures and their variants are often misdiagnosed,
      however, because of the numerous atypical presentations of this injury in
      children. This article describes the diagnosis, treatment, and potential pitfalls
      encountered in the treatment of Monteggia fractures.

PMID- 9758452
TI  - Clinical evaluation of the Alta hip bolt in peritrochanteric hip fractures.
AB  - We reviewed the clinical and radiographic results of 58 patients with
      peritrochanteric fractures treated with the Alta hip bolt (a sliding compression
      device that inserts a dome plunger in the femoral head instead of a hip screw).
      This group was compared with a group of 53 patients treated with conventional hip
      screws. Three patients (5.2%) treated with the Alta hip bolt and three patients
      (5.7%) treated with conventional hip screw had failure of fixation. Failure of
      fixation consistently occurred in patients with unstable fracture patterns or
      significant osteopenia. There were no cases of bolt cut-out in stable
      intertrochanteric fractures. We conclude that the Alta hip bolt performs as well
      as sliding hip screws in peritrochanteric fractures, but the additional learning
      curve and increased cost do not justify its routine use at this point in time.

PMID- 9758453
TI  - Use of an internal fixator device to treat comminuted fractures of the distal
      radius: report of a technique.
AB  - An internal fixator technique for stabilizing comminuted Colles fractures has
      been developed in the anatomy laboratory and used in 35 clinical cases. The
      Colles Fracture Plate (Biomet, Inc, Warsaw, Indiana) can be used to treat any
      comminuted Colles fracture for which an external fixator is considered proper
      management. We have determined, based on our surgical experience with both the
      internal and external fixator techniques, that internal fixation using the Colles
      Fracture Plate is technically just as simple as external fixation. In addition to
      requiring a significantly less expensive device, internal fixation using this
      technique offers the advantages of better patient acceptance and fewer
      complications. This report will be followed by a more comprehensive analysis of
      the technical outcome of this procedure to further substantiate the initial
      results presented here. The process of compiling and analyzing these data is
      under way.

PMID- 9758455
TI  - Fracture of the proximal tibia after anterior cruciate ligament reconstruction: a
      case report.
AB  - A case of fracture of the proximal tibia at the site of graft harvest for an
      anterior cruciate ligament reconstruction is reported. This fracture, at the
      distal edge of the harvest site on the tibial tubercle, was the result of stress
      concentration at this location. The patient's tibia fracture was treated with a
      long leg cast and healed without complication. Fracture of the patella at the
      graft harvest site has been reported as a complication of anterior cruciate
      ligament reconstruction. This is the first report of a fracture of the tibia at
      the site of graft harvest.

PMID- 9758454
TI  - Femoral osteomyelitis after tooth extraction.
AB  - Up to 35% of normal individuals may harbor Hemophilus aphrophilus in their
      oropharynx. Generally, this organism is well tolerated and rarely causes systemic
      infections; however, osteomyelitis may occur and it has previously been described
      involving the spine. Because of an intrinsic ability to inhibit leukocytes,
      osseous infections from this organism characteristically present in an insidious
      fashion. A case of severe femoral osteomyelitis after dental extraction is
      described.

PMID- 9758456
TI  - Problems of various fixation methods for open tibia fractures: experience in a
      Japanese level I trauma center.
AB  - Two hundred thirty-seven patients with open tibial fractures (245 fractures) were
      treated as follows: nonoperative stabilization alone (Nonop group, n = 54);
      immediate open reduction and internal fixation (ORIF group, n = 47); delayed ORIF
      (D-ORIF group, n = 109); or external fixation (EF group, n = 35). The D-ORIF
      group was further divided into ORIF after nonoperative treatment (Nonop/ORIF, n =
      86), and ORIF after external fixation (EF/ORIF, n = 23). The open tibial
      fractures were classified as follows: 42 type I (no infections), 107 type II (4
      infections), 43 type IIIA (3 infections), 42 type IIIB (12 infections), and 11
      type IIIC (2 infections), with significant differences in infection rate between
      type IIIB and type I, type II, or type IIIA. The deep infection rates in Nonop,
      ORIF, Nonop/ORIF, EF/ORIF, and EF groups were 3.7%, 12.8%, 5.8%, 30.4%, and 2.9%,
      respectively. There were significant differences in deep infection rates between
      the EF/ORIF and Nonop/ORIF, and the EF group. The mean period of fracture healing
      for type IIIB fractures was delayed. The mean time to union of the EF/ORIF was
      significantly longer than that of the ORIF, Nonop/ORIF, and EF groups,
      respectively. Complete and consecutive debridement procedures and early soft
      tissue coverage should be done to avoid wound infection, especially in type IIIB
      fractures. Delayed internal fixation after external fixation had the highest risk
      of infection, mandating meticulous wound management in such patients.

PMID- 9758457
TI  - Proximal locking screw repositioning in reconstruction femoral nails.
AB  - The proximal locking screws in reconstruction femoral nailing must be inserted
      properly. A targeting device that is not completely radiolucent can make precise
      positioning of these screws in the lateral plane difficult. We present a
      technique that we have used in osteoporotic bone to reposition screws that are
      not in the center of the femoral head on the lateral C-arm view.

PMID- 9758459
TI  - Manometric study of the effects of experimental fundoplication in rats.
AB  - BACKGROUND: The manometric effects of surgical repair of gastroesophageal reflux
      remain largely unknown, making the interpretation of the changes in the
      esophagogastric high pressure zone after fundoplication difficult. AIM: To
      measure in a murine model the transdiaphragmatic pressure gradients,
      intraabdominal esophageal length, and lower esophageal sphincter pressure and
      length after Nissen fundoplication. MATERIAL AND METHODS: Adult Wistar rats were
      divided into two groups Control group (n = 10): in which measurements were made
      after laparotomy and intraabdominal esophageal dissection. Nissen Group (n = 15):
      in which measurements were made at baseline, after fundoplication and 1 week
      after surgery. We considered the following variables: end-inspiratory and end
      expiratory transdiaphragmatic gradient (TDIG and TDEG respectively), lower
      esophageal sphincter pressure (LESP) length (LESL), and length of the
      intraabdominal segment of the esophagus (LIAS). RESULTS: The LIAS increased
      significantly after esophagogastric dissection in the control group (11.38 +/-
      3.22 mm vs 16.02 +/- mm, p < 0.05). No differences between pre- and postoperative
      status were found in TDIG, TDEG, LESP and LESL in the control group. However,
      LESP increased significantly after fundoplication (14.22 +/- 13.3 vs 32.96 +/-
      7.8 mmHg, p < 0.05) and these differences were still present one week later
      (30.72 +/- 6.73 mmHg, p < 0.05). LESL was also increased (1.91 +/- 1.76 mm vs
      7.68 +/- 1.83 mm) after fundoplication (p < 0.05), and reached 7.02 +/- 2.18 mm
      (p < 0.05) 1 week later. No differences were found in pre- and postoperative
      TDIG, TDEG and LIAS in the Nissen Group. CONCLUSION: In this murine experimental
      model, intraabdominal esophageal dissection increased the length of the
      intraabdominal esophagus without modifying the esophagogastric high pressure
      zone, while Nissen fundoplication increased lower esophageal sphincter pressure
      and length, without modifying the length of the intraabdominal esophagus or the
      transdiaphragmatic pressure gradients.

PMID- 9758460
TI  - Speech of the Health Minister to the BDA Conference 1998.

PMID- 9758458
TI  - The areA(r) mutation of Aspergillus nidulans confers low pH sensitivity in the
      presence of ammonium as the only nitrogen source.
AB  - The utilization of nitrogen sources by the fungus Aspergillus nidulans is
      controlled by a mechanism mediated by areA, a wide domain regulatory gene. It has
      been verified that the strains carrying the mutant allele areAr are inhibited
      when growing at low pH in the presence of ammonium as the only nitrogen source.
      The genetic analysis of this marker showed that it apparently maps at the areA
      locus.

PMID- 9758461
TI  - Developmental genetics of Drosophila. Special issue dedicated to Antonio Garcia
      Bellido.

PMID- 9758462
TI  - [Management of contact cheilitis in primary care].

PMID- 9758463
TI  - Peptide nucleic acid (PNA) from DNA recognition to antisense and DNA structure.
AB  - The biophysical and biological properties of PNA (peptide nucleic acid) is
      briefly reviewed with special emphasis on recent three dimensional structures of
      PNA-nucleic acid complexes and on structure-activity relations in terms of
      nucleic acid hybridization properties. 1997 Elsevier Science B.V.

PMID- 9758464
TI  - Consultants' merit award system to be reformed.

PMID- 9758465
TI  - Telephone advice scheme criticised.

PMID- 9758466
TI  - Organophosphate pesticides are being tested on students.

PMID- 9758467
TI  - China to expand rural healthcare system.

PMID- 9758468
TI  - Heroin use among young people is increasing in England and Wales.

PMID- 9758469
TI  - Should doctors perform an elective caesarean section on request? Maternal choice
      alone should not determine method of delivery.

PMID- 9758470
TI  - Risk of connective tissue disease among women with breast implants. Authors
      should have made better use of matched control group.

PMID- 9758471
TI  - Diagnosis of Creutzfeldt-Jakob disease by measurement of S100 protein in serum.
      Tonsil biopsy helps diagnose new variant Creutzfeldt-Jakob disease.

PMID- 9758472
TI  - Use of statins. But New Zealand tables are better.

PMID- 9758473
TI  - Career options available to general practitioner assistants. Reply by chairman of
      General Practitioners Committee's medical work force subcommittee.

PMID- 9758474
TI  - Postnatal health education in Nepal. There are no shortcuts.

PMID- 9758475
TI  - Postnatal health education in Nepal. Quality of health education was not measured
      objectively.

PMID- 9758477
TI  - Users of NHS will be surveyed.

PMID- 9758476
TI  - Cardiac surgery inquiry given wide remit.

PMID- 9758478
TI  - Quality of UK milk to be studied.

PMID- 9758479
TI  - Two Scottish surgeons suspended.

PMID- 9758480
TI  - Prognosis of symptoms that are medically unexplained. Clinical guidelines are
      needed.

PMID- 9758481
TI  - Prognosis of symptoms that are medically unexplained. Follow up study needs to be
      continued for longer.

PMID- 9758482
TI  - Prognosis of symptoms that are medically unexplained. Psychological aspects of
      investigations must be addressed early.

PMID- 9758483
TI  - Relation of rates of self referral to A&E departments to deprivation. Distance
      from department and deprivation are both important in explaining variations in
      rates.

PMID- 9758484
TI  - Bereavement in adult life. Psychotropic drugs may be appropriate treatment.

PMID- 9758485
TI  - Pressures in outpatient clinics. Increasing numbers of ward referrals are an
      additional pressure.

PMID- 9758486
TI  - Magnesium sulphate in pre-eclampsia. Still room for improvement.

PMID- 9758487
TI  - Human fertilisation and Embryology Act 1990 discriminates against girls.

PMID- 9758488
TI  - Carcinogen in tobacco smoke can be passed to fetus.

PMID- 9758489
TI  - Tuberculosis controls in Philippines have failed so far.

PMID- 9758490
TI  - Treating chronic fatigue with exercise. Exercise improves mood and sleep.

PMID- 9758491
TI  - Treating chronic fatigue with exercise. Results are contradictory for patients
      meeting different diagnostic criteria.

PMID- 9758492
TI  - Hypoxic responses in infants. Research should contain element of treatment.

PMID- 9758493
TI  - Hypoxic responses in infants. No known mechanism links hypoxia and sudden infant
      death syndrome.

PMID- 9758494
TI  - Hypoxic responses in infants. Danger to babies from air travel must be small.

PMID- 9758495
TI  - Hypoxic responses in infants. Study methods need to be appropriate.

PMID- 9758496
TI  - Hypoxic responses in infants. Public must be warned of weak evidence for risk of
      serious harm.

PMID- 9758497
TI  - Hypoxic responses in infants. Risks associated with hypoxia during flights need
      to be investigated.

PMID- 9758498
TI  - Helicobacter pylori and surgery. Helicobacter pylori is merely suppressed by
      bile.

PMID- 9758499
TI  - Helicobacter pylori and surgery. Role of bile reflux is insufficiently explained.

PMID- 9758500
TI  - Helicobacter pylori and surgery. Authors should not extrapolate findings into
      unresearched areas.

PMID- 9758501
TI  - Screening for Chlamydia trachomatis. Contacts attendance rate is 70% in
      Hertfordshire.

PMID- 9758502
TI  - Screening for Chlamydia trachomatis. Genitourinary medicine clinics in Scotland
      give high priority to contact tracing.

PMID- 9758503
TI  - Screening for Chlamydia trachomatis. New technologies enable screening to be
      carried out in schools and the community.

PMID- 9758504
TI  - Screening for Chlamydia trachomatis. Screening for and treatment of chlamydial
      infection demand commitment.

PMID- 9758505
TI  - Central venous catheters and infection. Routine placement of central venous
      catheters should be retained.

PMID- 9758506
TI  - Central venous catheters and infection. Colonisation of lines does not cause
      complications, but insertion does.

PMID- 9758507
TI  - Central venous catheters and infection. Use of antimicrobial catheters needs to
      undergo trials.

PMID- 9758508
TI  - Consumers. Relative care.

PMID- 9758509
TI  - Flow cytometric detection of proliferation-associated antigens, PCNA and Ki-67.

PMID- 9758510
TI  - 1st International Congress on Endoscope-assisted Microneurosurgery. Abstracts.

PMID- 9758511
TI  - [Niemann-Pick disease (type C)].

PMID- 9758513
TI  - Nuclear cardiology in the literature.

PMID- 9758512
TI  - Characterization of cyanogen bromide fragments of reduced human serum albumin by
      matrix-assisted laser desorption/ionization mass spectrometry.

PMID- 9758514
TI  - Must a physician be present for both a stress test and the imaging, or may this
      be handled by technologist.

PMID- 9758515
TI  - The Asian Women's Health Clinic: addressing cultural barriers to preventive
      health care.

PMID- 9758516
TI  - Private sector becoming the key to research funding in Canada.
AB  - The private sector, and drug companies in particular, are beginning to play a
      much stronger and visible role in funding health care research in canada. The
      implications of this change were discussed at a recent conference.

PMID- 9758517
TI  - Controlling health care costs a costly business for HMOs in US.

PMID- 9758518
TI  - Proceedings of the 10th International Conference on Partitioning in Aqueous Two
      Phase Systems. Reading, United Kingdom, 10-15 August 1997.

PMID- 9758519
TI  - What's in a name.

PMID- 9758520
TI  - What's in a name.

PMID- 9758521
TI  - What are family planning clinics for.

PMID- 9758522
TI  - What are family planning clinics for.

PMID- 9758523
TI  - What are family planning clinics for.

PMID- 9758524
TI  - How should induced abortion rates be measured.

PMID- 9758525
TI  - What are family planning clinics for.

PMID- 9758526
TI  - Pregnancy while using Norplant.

PMID- 9758527
TI  - The view from Haringey.

PMID- 9758528
TI  - Guidelines for pediatric equipment and supplies for basic and advanced life
      support ambulances.

PMID- 9758530
TI  - USAN Council. List No.407. New names. Lenercept.

PMID- 9758531
TI  - USAN Council. List No.407. New names. Trafermin.

PMID- 9758529
TI  - An abbreviated account.

PMID- 9758533
TI  - Catecholamines and the cardiovascular system. Proceedings of a meeting. Sophia
      Antipolis, France, 4-6 December 1997.

PMID- 9758532
TI  - Proceedings of the Brenot Memorial Symposium on the Pathogenesis of Primary
      Pulmonary Hypertension. Corisca, July 29-31, 1997.

PMID- 9758535
TI  - Renin-angiotensin in preascitic cirrhosis: evidence for primary peripheral
      arterial vasodilation.

PMID- 9758534
TI  - Gut patterning: the case of the missing cecum.

PMID- 9758536
TI  - Pancreatic stellate cells: the new stars of chronic pancreatitis?

PMID- 9758537
TI  - Tolerance and sensitivity: ethanol and Kupffer cells.

PMID- 9758538
TI  - Optical coherence tomography: lighting the way around optical biopsy.

PMID- 9758539
TI  - In search of the cause of idiopathic intestinal pseudo-obstruction: is there a
      viral etiology?

PMID- 9758540
TI  - The energy to make acid.

PMID- 9758541
TI  - Interferon alfa for chronic hepatitis C: how do we define cure?

PMID- 9758542
TI  - Therapy for hepatorenal syndrome.

PMID- 9758543
TI  - Cholic acid synthesis from 27-hydroxycholesterol in humans.

PMID- 9758544
TI  - Gastrin sensitivity and acid in H. pylori: revisited.

PMID- 9758545
TI  - Helicobacter pylori and acid secretion.

PMID- 9758546
TI  - Resistant starch and SCFA: adjunct to ORS?

PMID- 9758547
TI  - H. pylori eradication and gastric precancerous lesions.

PMID- 9758548
TI  - Potential population-wide impact of aspirin on colon cancer mortality.

PMID- 9758549
TI  - Swallowing and LES relaxation with reflux: not by chance.

PMID- 9758550
TI  - Identification and mutation analysis of a cochlear-expressed, zinc finger protein
      gene at the DFNB7/11 and dn hearing-loss loci on human chromosome 9q and mouse
      chromosome 19.
AB  - The DFNB7/11 locus for autosomal recessive non-syndromic hearing loss (ARNSHL)
      has been mapped to an approx. 1.5 Mb interval on human chromosome 9q13-q21. We
      have determined the cDNA sequence and genomic structure of a novel cochlear
      expressed gene, ZNF216, that maps to the DFNB7/11 interval. The mouse orthologue
      of this gene maps to the murine dn (deafness) locus on mouse chromosome 19. The
      ZNF216 gene is highly conserved between human and mouse, and contains two regions
      that show homology to the putative zinc linger domains of other proteins. To
      determine it mutations in ZNF216 might be the cause of hearing loss at the
      DFNB7/11 locus, we screened the coding region of this gene in DFNB7/11 families
      by direct sequencing. No potential disease-causing mutations were found. In
      addition, Northern blot analysis showed no difference in ZNF216 transcript size
      or abundance between dn and control mice. These data Suggest that the ZNF216 gene
      is unlikely to be responsible for hearing loss at the DFNB7/11 and dn loci.

PMID- 9758551
TI  - Genotypically dependent effects of cyromazine on reproduction and offspring
      development in the Australian Lucilia cuprina (Diptera: Calliphoridae).
AB  - The effects of cyromazine on egg production and subsequent egg-to-adult survival
      were examined on susceptible, heterozygous, and homozygous cyromazine-resistant
      genotypes of the Australian sheep blowfly Lucilia cuprina (Wiedemann) by
      administering to adults 10 ppm of cyromazine in drinking water. Cyromazine
      reduced egg production, hatch, and subsequent larval survival in susceptible
      genotypes by acting at the embryonic stage of development. Resistance negated
      these effects dominantly for egg production and egg hatch and in a partially
      dominant manner for egg-to-adult survivorship.

PMID- 9758552
TI  - [Hepatocyte nuclear factor 6: a novel class of liver-enriched transcription
      factor].

PMID- 9758553
TI  - Thrombogenic and atherogenic lipid modifications in plasma and patients with
      coronary artery disease and after coronary artery bypass surgery.

PMID- 9758554
TI  - [Alzheimer disease. Pseudo-irreversible AChE inhibition with rivastigmine].

PMID- 9758555
TI  - [Alzheimer disease. Irreversible AChE inhibition with metrifonate].

PMID- 9758556
TI  - [Application of lymphoscintigraphy in post-mastectomy lymphedema of the upper
      extremities].

PMID- 9758557
TI  - [Participation of interleukin-6 to skeletal muscle proteolysis: the effect of IL
      6 administration on mRNA expression by the skeletal muscle cell proteolytic
      system].

PMID- 9758558
TI  - [Trial determination of bile flow volume in the common bile duct by using a
      transit time ultrasonic flowmeter--in relation to the contractile movement of the
      duodenum].

PMID- 9758559
TI  - [Effect of Lazaroid U-74389G on ischemic reperfusion injury of the lung].

PMID- 9758560
TI  - Vestibular Adaptation. Proceedings of a conference. Santa Monica, California,
      USA. May 23-25, 1996.

PMID- 9758561
TI  - Bibliography of Neville Butler.

PMID- 9758562
TI  - Human Rights and Dignity in the Practice of Medicine. Proceedings of an
      International Medical Symposium. Copenhagen, Denmark, September 21-22, 1996.

PMID- 9758563
TI  - Voorjaarsdagen Congress 1998. Amsterdam, April 24-26, 1998. Proceedings.

PMID- 9758564
TI  - The animal as a companion; the characteristics of a symbiosis.

PMID- 9758565
TI  - Vet faces monkey.

PMID- 9758566
TI  - Marketing and management of practice services.

PMID- 9758567
TI  - Competition or cooperation?

PMID- 9758568
TI  - Febrile nonresponsiveness of vagotomized animals: is it due to endotoxin
      translocation from the gut and tolerance?

PMID- 9758569
TI  - Radiologists' review of radiographs.

PMID- 9758570
TI  - Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study.
AB  - BACKGROUND: High intake of folate may reduce risk for colon cancer, but the
      dosage and duration relations and the impact of dietary compared with
      supplementary sources are not well understood. OBJECTIVE: To evaluate the
      relation between folate intake and incidence of colon cancer. DESIGN: Prospective
      cohort study. SETTING: 88,756 women from the Nurses' Health Study who were free
      of cancer in 1980 and provided updated assessments of diet, including
      multivitamin supplement use, from 1980 to 1994. PATIENTS: 442 women with new
      cases of colon cancer. MEASUREMENTS: Multivariate relative risk (RR) and 95% CIs
      for colon cancer in relation to energy-adjusted folate intake. RESULTS: Higher
      energy-adjusted folate intake in 1980 was related to a lower risk for colon
      cancer (RR, 0.69 [95% CI, 0.52 to 0.93] for intake > 400 microg/d compared with
      intake < or = 200 microg/d) after controlling for age; family history of
      colorectal cancer; aspirin use; smoking; body mass; physical activity; and
      intakes of red meat, alcohol, methionine, and fiber. When intake of vitamins A,
      C, D, and E and intake of calcium were also controlled for, results were similar.
      Women who used multivitamins containing folic acid had no benefit with respect to
      colon cancer after 4 years of use (RR, 1.02) and had only nonsignificant risk
      reductions after 5 to 9 (RR, 0.83) or 10 to 14 years of use (RR, 0.80). After 15
      years of use, however, risk was markedly lower (RR, 0.25 [CI, 0.13 to 0.51]),
      representing 15 instead of 68 new cases of colon cancer per 10,000 women 55 to 69
      years of age. Folate from dietary sources alone was related to a modest reduction
      in risk for colon cancer, and the benefit of long-term multivitamin use was
      present across all levels of dietary intakes. CONCLUSIONS: Long-term use of
      multivitamins may substantially reduce risk for colon cancer. This effect may be
      related to the folic acid contained in multivitamins.

PMID- 9758571
TI  - Efficacy and tolerability of stavudine plus lamivudine in treatment-naive and
      treatment-experienced patients with HIV-1 infection.
AB  - BACKGROUND: A combination of two nucleoside analogues is currently the core of
      any antiretroviral regimen for HIV-1 infection. Stavudine plus lamivudine has
      shown an additive effect in vitro, as well as an absence of overlapping toxicity
      and cross-resistance. OBJECTIVE: To evaluate the antiviral efficacy of stavudine
      plus lamivudine in treatment-naive patients and in patients previously treated
      with other nucleoside reverse transcriptase inhibitors. DESIGN: Prospective, open
      label pilot study. SETTING: Three urban clinical centers in Paris. PATIENTS: 83
      patients with CD4+ cell counts between 50 and 400 cells/mm3 (42 treatment-naive
      and 41 treatment-experienced patients). INTERVENTIONS: Stavudine, 40 mg twice
      daily (30 mg twice daily in patients with a body weight < or = 60 kg), and
      lamivudine, 150 mg twice daily. MEASUREMENTS: Primary end points for efficacy
      included changes in plasma viral load and CD4+ cell count at 24 weeks compared
      with baseline. RESULTS: Therapy with stavudine plus lamivudine resulted in a
      median decrease of 1.66 log10 (10(1.66)) (range, -3.04 to -0.79 log10) in plasma
      HIV-1 RNA; the median increase in CD4+ cell count was 108 cells/mm3 (range, -58
      to 406 cells/mm3) at week 24 in treatment-naive patients. In treatment
      experienced patients, the median reduction in plasma HIV-1 RNA was 0.55 log10
      (range, -2.86 to 0.52 log10), and the median increase in CD4+ cell count was 46
      cells/mm3 (range, -188 to 311 cells/mm3). The percentages of patients with less
      than 3000 HIV-1 RNA copies/mL and less than 400 copies/mL at 24 weeks were,
      respectively, 57% (95% CI, 41% to 72%) and 26% (CI, 12% to 40%) among treatment
      naive patients and 22% (CI, 10% to 38%) and 5% (CI, 1% to 17%) among treatment
      experienced patients. Of 82 patients, 14 (17%) experienced grade 3 or 4 toxicity
      and 2 discontinued therapy because of intolerance toward treatment. CONCLUSION:
      Stavudine plus lamivudine seems to have a potent antiviral effect in treatment
      naive and treatment-experienced patients. No major drug-limiting toxicity was
      found. This two-nucleoside combination should be considered in multidrug therapy
      for HIV.

PMID- 9758572
TI  - Relation of family responsibilities and gender to the productivity and career
      satisfaction of medical faculty.
AB  - BACKGROUND: Studies have found that female faculty publish less, have slower
      career progress, and generally have a more difficult time in academic careers
      than male faculty. The relation of family (dependent) responsibilities to gender
      and academic productivity is unclear. OBJECTIVE: To describe dependent
      responsibilities by gender and to identify their relation to the aspirations,
      goals, rate of progress, academic productivity, and career satisfaction of male
      and female medical school faculty. DESIGN: 177-item survey questionnaire.
      SETTING: 24 randomly selected medical schools in the contiguous United States.
      PARTICIPANTS: 1979 respondents from a probability sample of full-time academic
      medical school faculty. MEASUREMENTS: The main end point for measuring academic
      productivity was the total number of publications in refereed journals. Perceived
      career progress and career satisfaction were assessed by using Likert scales.
      RESULTS: For both male and female faculty, more than 90% of time devoted to
      family responsibilities was spent on child care. Among faculty with children,
      women had greater obstacles to academic careers and less institutional support,
      including research funding from their institutions (46% compared with 57%; P <
      0.001) and secretarial support (0.68 full-time equivalents compared with 0.83
      full-time equivalents; P = 0.003), than men. Compared with men with children,
      women with children had fewer publications (18.3 compared with 29.3; P < 0.001),
      slower self-perceived career progress (2.6 compared with 3.1; P < 0.001), and
      lower career satisfaction (5.9 compared with 6.6; P < 0.001). However, no
      significant differences between the sexes were seen for faculty without children.
      CONCLUSIONS: Compared with female faculty without children and compared with men,
      female faculty with children face major obstacles in academic careers. Some of
      these obstacles can be easily modified (for example, by eliminating after-hours
      meetings and creating part-time career tracks). Medical schools should address
      these obstacles and provide support for faculty with children.

PMID- 9758573
TI  - Diagnosis of familial Mediterranean fever by a molecular genetics method.
AB  - BACKGROUND: Familial Mediterranean fever is a recessively inherited disorder
      characterized by episodes of fever with abdominal pain, pleurisy, or arthritis.
      The familial Mediterranean fever gene, designated MEFV, was recently cloned, and
      at least three missense mutations (M6801, M694V, and V726A) that account for a
      large percentage of patients with this disease were identified. OBJECTIVE: To
      establish a diagnostic test for familial Mediterranean fever. DESIGN: Cross
      sectional study of a convenience sample of patients attending familial
      Mediterranean fever clinics. SETTING: Tertiary referral hospitals. PATIENTS: 107
      patients with familial Mediterranean fever, their family members, and controls.
      MEASUREMENTS: Mutations in the 107 samples were assessed by amplifying genomic
      DNA with use of primers that selectively amplify the normal or altered DNA
      sequence of the 3 MEFV mutations (amplification refractory mutation system
      [ARMS]). Mutations were independently assessed by automated sequencing of genomic
      DNA amplified by polymerase chain reaction to evaluate the sensitivity and
      specificity of the ARMS assay. RESULTS: The ARMS assay correctly identified
      M6801, M694V, and V726A mutations in 82 persons with mutations documented by DNA
      sequencing (21 homozygotes, 2 compound heterozygotes, and 59 simple
      heterozygotes). Of 7 persons known from family studies to be noncarriers and 18
      unrelated persons who were negative for these mutations by sequencing, none had
      MEFV mutations according to ARMS. CONCLUSION: The ARMS assay is a rapid, cost
      effective, and accurate method for detecting three common mutations in familial
      Mediterranean fever.

PMID- 9758575
TI  - Effect of proton-pump inhibitor therapy on diagnostic testing for Helicobacter
      pylori.
AB  - BACKGROUND: Proton-pump inhibitor therapy may cause false-negative results on
      Helicobacter pylori diagnostic testing. OBJECTIVE: To determine the frequency and
      duration of conversion of urea breath test results from positive to negative in
      patients given a proton-pump inhibitor. SETTING: Two urban university
      gastroenterology clinics. PATIENTS: Patients infected with H. pylori who had
      positive results on urea breath tests. INTERVENTION: Lansoprazole, 30 mg/d for 28
      days. MEASUREMENTS: The urea breath test was repeated at 28 days. If the results
      were negative, testing was repeated 3, 7, 14, and 28 days after completion of
      therapy until the results reverted to positive. RESULTS: 31 (33%) of 93 patients
      in whom H. pylori was not eradicated had a negative breath test result while
      receiving lansoprazole. The proportions of patients whose breath test results
      were positive after completion of lansoprazole therapy were 91% (95% CI, 83% to
      96%) at 3 days, 97% (CI, 90% to 99%) at 7 days, and 100% (CI, 96% to 100%) at 14
      days. CONCLUSION: Patients should not receive proton-pump inhibitors for 2 weeks
      before receiving the urea breath test for H. pylori infection.

PMID- 9758574
TI  - Employment after coronary angioplasty or coronary bypass surgery in patients
      employed at the time of revascularization.
AB  - BACKGROUND: Patients who undergo coronary angioplasty have a shorter
      convalescence than those who undergo coronary bypass surgery. This may improve
      subsequent employment. OBJECTIVE: To compare employment patterns after coronary
      angioplasty or surgery. DESIGN: Multicenter, randomized clinical trial. SETTING:
      Seven tertiary care hospitals. PATIENTS: 409 employed patients with multivessel
      coronary artery disease. INTERVENTION: Coronary bypass surgery or balloon
      angioplasty. MEASUREMENTS: Time to return to work and time spent working during 4
      years of follow-up. RESULTS: Patients who underwent angioplasty returned to work
      6 weeks sooner than patients who underwent coronary bypass surgery (P < 0.001),
      but long-term employment did not differ significantly (P > 0.2). Long-term
      employment was significantly lower among patients who were 60 to 64 years of age
      (P < 0.001), those who worked less than full-time at study entry (P < 0.001), and
      those who had less formal education (P = 0.005). Patients with only one source of
      health insurance were more likely to continue working (P = 0.005). CONCLUSIONS:
      Faster recovery after angioplasty speeds return to work but does not improve long
      term employment, which is primarily associated with nonmedical factors.

PMID- 9758576
TI  - Update in women's health.

PMID- 9758577
TI  - Infections in patients with chronic lymphocytic leukemia treated with
      fludarabine.
AB  - BACKGROUND: Fludarabine, a purine analogue with activity in chronic lymphocytic
      leukemia, is usually well tolerated. Although serious infections after
      fludarabine therapy have been described, a systematic analysis of the risk
      factors for such infections in chronic lymphocytic leukemia is lacking.
      OBJECTIVE: To determine the risk factors for major infection in patients with
      chronic lymphocytic leukemia treated with fludarabine. DESIGN: Retrospective
      review of medical records. SETTING: Cancer center. PATIENTS: 402 patients with
      chronic lymphocytic leukemia not previously treated or treated with chlorambucil
      (with or without prednisone) who received fludarabine (30 mg/m2 of body surface
      area per day for 5 days) with or without prednisone at 4-week intervals. RESULTS:
      Infections occurred more often in previously treated (144 of 248 [58%]) than in
      previously untreated (53 of 154 [34%]) patients (P < 0.001). Listeriosis or
      pneumocystosis occurred in 12 of 170 (7%) previously treated patients receiving
      fludarabine plus prednisone, 0 of 78 previously treated patients receiving
      fludarabine alone, and 2 of 154 (1%) previously untreated patients receiving
      fludarabine plus prednisone (P = 0.003). Univariate analysis identified previous
      chemotherapy, advanced disease, failure to respond to fludarabine, elevated serum
      beta2-microglobulin level (P < 0.001), low serum albumin level (P = 0.024),
      elevated serum creatinine concentration (P = 0.008), and low granulocyte count (P
      = 0.003) as risk factors for infection. Multivariate analysis identified Rai
      stage III or IV (odds ratio, 1.98 [95% CI, 1.17 to 3.94]), previous treatment
      (odds ratio, 2.24 [CI, 1.43 to 3.51]), and elevated serum creatinine
      concentration (odds ratio, 1.98 [CI, 1.09 to 3.67]) as statistically significant
      independent risk factors for major infection. A baseline granulocyte count of
      more than 1000 cells/microL was protective (odds ratio, 0.54 [CI, 0.29 to 0.99]).
      Five (26%) of 19 patients with a CD4 count less than 50 cells/mL developed
      cutaneous zoster compared with 9 (6%) of 139 patients with a CD4 count greater
      than 50 cells/mL (P = 0.01). CONCLUSIONS: Fludarabine used in previously treated
      patients with chronic lymphocytic leukemia may be associated with infections
      involving T-cell dysfunction, such as listeriosis, pneumocystosis, mycobacterial
      infections, and opportunistic fungal and viral infections. Prophylaxis or
      presumptive therapy should be initiated in the appropriate setting.

PMID- 9758578
TI  - A survey of provider experiences and perceptions of preferential access to
      cardiovascular care in Ontario, Canada.
AB  - BACKGROUND: The public health insurance system in Canada is predicated on equal
      access to care for persons in need. OBJECTIVE: To determine the views and
      experiences of Ontario physicians and hospital administrators in providing
      patients with preferential access to specialized cardiovascular care on the basis
      of nonclinical factors. DESIGN: Survey with self-administered questionnaire.
      SETTING: Ontario, Canada. PARTICIPANTS: All Ontario cardiologists (n = 268),
      cardiac surgeons (n = 68), and hospital chief executives (n = 218) and random
      samples of internists (n = 300) and family physicians (n = 300). MEASUREMENTS:
      Elicited responses (yes or no) to questions on whether and why preferential
      access occurred and whether the respondents had been personally involved in such
      a situation. RESULTS: After undeliverable surveys and respondents no longer
      involved with acute care were excluded, the eligible response rate was 71.3% (788
      of 1105 respondents). More than 80% of physicians and 53% of hospital chief
      executives had been personally involved in managing a patient who had received
      preferential access on the basis of factors other than medical need. Patients
      deemed most likely to receive such treatment were those with personal ties to the
      treating physicians (93% [95% CI, 91% to 95%]), high-profile public figures (85%
      [CI, 82% to 87%]), and politicians (83% [CI, 80% to 86%]). Physicians were
      significantly more likely than chief executives to indicate that hospital board
      members (81% and 68%; P < 0.001) and donors to hospital foundations (63% and 42%;
      P < 0.001) would receive preferential access. Most respondents indicated that
      preferential access was more likely to be provided if patients or families were
      well informed, aggressive, or potentially litigious. The survey did not permit
      estimation of the frequency of episodes of preferential access. CONCLUSIONS:
      Although equality of access is a cornerstone principle of Canada's universal
      health care system, some access to specialized cardiovascular services occurs
      preferentially on the basis of factors other than clinical need. The actual
      magnitude and consequences of this phenomenon remain unknown.

PMID- 9758579
TI  - Rethinking nonadherence: historical perspectives on triple-drug therapy for HIV
      disease.
AB  - The advent of triple-drug therapy for HIV disease has raised the concern that
      disadvantaged patients with multiple social problems may be nonadherent to
      treatment. Fearing that partial adherence will lead to drug resistance, some
      clinicians are withholding these powerful new drugs from such patients. The
      historical record demonstrates that labeling patients as nonadherent may be both
      stigmatizing and inaccurate. Since 1900, such adjectives as ignorant, vicious,
      and recalcitrant have been used to describe patients who do not follow medical
      advice. Less judgmental terms, such as nonadherent and noncompliant, are now
      used, but these terms still imply that patients should obey physician-imposed
      regimens. Studies of nonadherence have consistently shown that the problem is
      widespread among all persons and cannot reliably be predicted on the basis of
      patient characteristics. This paper argues that physicians should deemphasize the
      standard approach of predicting and correcting nonadherent behavior in certain
      patients. Rather, clinicians should encourage all HIV-positive patients to devise
      individualized treatment plans that can facilitate reliable ingestion of
      medication. Although the potential development of resistance to triple-drug
      therapy remains an important public health issue, concern about this possibility
      must be balanced with respect for patients' rights. Encouraging the active
      participation of HIV-positive persons in their own treatment will help avoid
      judgmental and inaccurate assessments of patient behavior and may help patients
      take medications more successfully.

PMID- 9758580
TI  - On being Dr. Mom.

PMID- 9758581
TI  - Genetics of familial Mediterranean fever and its implications.

PMID- 9758582
TI  - Lyme disease vaccines.

PMID- 9758583
TI  - Hemochromatosis and diabetes mellitus.

PMID- 9758584
TI  - Dehydroepiandrosterone, insulin-like growth factor-I, and prostate cancer.

PMID- 9758585
TI  - Dehydroepiandrosterone and cardiac arrhythmia.

PMID- 9758586
TI  - Multiple IgA autoantibodies associated with mefenamic acid.

PMID- 9758587
TI  - In the name of medicine.

PMID- 9758588
TI  - In the name of medicine.

PMID- 9758589
TI  - History corner: wash the sand out of the sponges.

PMID- 9758590
TI  - Is it research or quality improvement?

PMID- 9758591
TI  - Power perceived is power achieved.

PMID- 9758592
TI  - Family-centered perioperative nursing care takes on a new look.

PMID- 9758593
TI  - Molecular evolution of spectrin repeats.

PMID- 9758594
TI  - Mixed messages: presentation of information in cystic fibrosis-screening
      pamphlets.
AB  - Written pamphlets are an important source of information for individuals deciding
      whether to undergo carrier testing for cystic fibrosis (CF). Adequate
      understanding of the condition and reproductive options following the diagnosis
      of a fetus with CF are critical to informed decision making. The information
      given about CF and reproductive options in 28 pamphlets about carrier testing,
      from commercial and noncommercial organizations in the United States and the
      United Kingdom, aimed at prenatal and other populations, was assessed. The amount
      of information provided about CF showed a range of 1-37 sentences (median 6.5),
      with most being relatively neutral and with a minority conveying a positive or a
      negative image. Positive sentences were less common in British, U.S. commercial,
      and prenatal pamphlets. Statements about life expectancy also varied
      considerably, both in the ages provided and in the degree of optimism conveyed.
      In addition, the pamphlets varied in the amount of information they provided
      about reproductive options following the diagnosis of a fetus with CF. Abortion
      was mentioned in just 15 pamphlets, more often in the United Kingdom than in the
      United States and more frequently in pamphlets from noncommercial than in those
      from commercial organizations. Wide variation in the descriptions of CF and the
      reproductive options presented raises concerns about the extent to which any one
      pamphlet may present balanced information. The choices about what information to
      include in educational materials need to be explicitly considered on the basis of
      the message intended to be sent.

PMID- 9758596
TI  - Multiple phenotype modeling in gene-mapping studies of quantitative traits: power
      advantages.
AB  - Genomewide searches for loci influencing complex human traits and diseases such
      as diabetes, hypertension, and obesity are often plagued by low power and
      interpretive difficulties. Attempts to remedy these difficulties have typically
      relied on, and have promoted the use of, novel subject-ascertainment schemes,
      larger sample sizes, a greater density of DNA markers, and more-sophisticated
      statistical modeling and analysis strategies. Many of these remedies can be
      costly to implement. We investigate the utility of a simple statistical model for
      the mapping of quantitative-trait loci that incorporates multiple phenotypic or
      diagnostic endpoints into a gene-mapping analysis. The approach considers finding
      a linear combination of multiple phenotypic values that maximizes the evidence
      for linkage to a locus. Our results suggest that substantial increases in the
      power to map loci can be obtained with the proposed technique, although the
      increase in power obtained is a function of the size and direction of the
      residual correlation among the phenotypes used in the analysis. Extensive
      simulation studies are described that justify these claims, for cases in which
      two phenotypic measures are analyzed. This approach can be easily extended to
      cover more-complex situations and may provide a basis for more insightful genetic
      analysis paradigms.

PMID- 9758595
TI  - An analysis of phenotypic variation in the familial cancer syndrome von Hippel
      Lindau disease: evidence for modifier effects.
AB  - von Hippel-Lindau disease (VHL) is a dominantly inherited familial cancer
      syndrome predisposing to ocular and CNS hemangioblastomas, renal-cell carcinoma
      (RCC), and pheochromocytoma. Both interfamilial and intrafamilial variability in
      expression is well recognized. Interfamilial differences in pheochromocytoma
      susceptibility have been attributed to allelic heterogeneity such that specific
      missense germ-line mutations confer a high risk for this complication. However,
      in most cases, tumor susceptibility does not appear to be influenced by the type
      of underlying VHL mutation. To probe the causes of phenotypic variation, we
      examined 183 individuals with germ-line VHL gene mutations, for the presence and
      number of ocular tumors. The prevalence of ocular angiomatosis did not increase
      with age, and the distribution of these tumors in gene carriers was significantly
      different than the expected stochastic distributions. Individuals with ocular
      hemangioblastomas had a significantly increased incidence of cerebellar
      hemangioblastoma and RCC (hazard ratios 2.3 and 4.0, respectively). The number of
      ocular tumors was significantly correlated in individuals of 12 degree
      relatedness but not in more distantly related individuals. These findings suggest
      that the development of VHL ocular tumors is determined at an early age and is
      influenced by genetic and/or environmental modifier effects that act at multiple
      sites. Functional polymorphisms in the glutathione-S-transferase M1 gene (GSTM1)
      or the cytochrome P450 2D6 gene (CYP2D6) did not show a significant association
      with the severity of ocular or renal involvement.

PMID- 9758597
TI  - Imprinted expression of SNRPN in human preimplantation embryos.
AB  - Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two clinically
      distinct neurogenetic disorders arising from a loss of expression of imprinted
      genes within the human chromosome region 15q11-q13. Recent evidence suggests that
      the SNRPN gene, which is defective in PWS, plays a central role in the imprinting
      center regulation of the PWS/AS region. To increase our understanding of the
      regulation of expression of this imprinted gene, we have developed single-cell
      sensitive procedures for the analysis of expression of the SNRPN gene during
      early human development. Transcripts of SNRPN were detected in human oocytes and
      at all stages of preimplantation development analyzed. Using embryos heterozygous
      for a polymorphism within the SNRPN gene, we showed that monoallelic expression
      from the paternal allele occurs by the 4-cell stage. Thus, the imprinting
      epigenetic information inherited in the gametes is recognized already in the
      preimplantation embryo. The demonstration of monoallelic expression in embryos
      means that efficient preimplantation diagnosis of PWS may be made by analysis for
      the presence or absence of SNRPN mRNA.

PMID- 9758598
TI  - Double heterozygotes for the Ashkenazi founder mutations in BRCA1 and BRCA2
      genes.

PMID- 9758599
TI  - A chromosomal deletion map of human malformations.
AB  - Malformations are common causes of pediatric morbidity and mortality, and genetic
      factors are a significant component of their etiology. Autosomal deletions, in
      almost all cases, cause a nonspecific embryopathy that presents after birth as
      growth failure, mental retardation, and multiple malformations. We have
      constructed a chromosome map of autosomal deletions associated with 47 different
      congenital malformations, using detailed clinical and cytogenetic information on
      1,753 patients with nonmosaic single contiguous autosomal deletions. The 1,753
      deletions involved 258 (89%) of 289 possible autosomal bands (by the use of ISCN
      400-band nomenclature), giving a total of 4,190 deleted autosomal bands for
      analysis. We compared the band distributions of deletions associated with common
      major malformations with the distribution of all 1,753 deletions. We noted 283
      positive associations between deleted bands and specific malformations, of which
      199 were significant (P<.05, P>.001) and 84 were highly significant (P<.001).
      These "malformation-associated bands" (MABs) were distributed among 137
      malformation-associated chromosome regions (MACRs). An average of 6 MABs in 2.9
      MACRs were detected per malformation studied; 18 (6%) of 283 MABs contain a locus
      known to be associated with the particular malformation. A further 18 (6%) of 283
      are in seven recognized specific malformation-associated aneuploid regions.
      Therefore, 36 (26%) of 137 of the MACRs contain an MAB coinciding with a
      previously recognized locus or malformation-associated aneuploid region. This map
      should facilitate identification of genes important in human development.

PMID- 9758601
TI  - mtDNA suggests Polynesian origins in Eastern Indonesia.

PMID- 9758600
TI  - Prenatal screening for cystic fibrosis carriers: an economic evaluation.
AB  - The cloning of the CFTR gene has made it technically possible to avert the
      unwanted birth of a child with cystic fibrosis (CF). Several large trials
      offering prenatal CF carrier screening suggest that such screening is practical
      and that identified carriers generally use the information obtained. Therefore, a
      critical question is whether the cost of such screening is justified. Decision
      analysis was performed that used information about choices that pregnant women
      were observed to make at each stage in the Rochester prenatal carrier-screening
      trial. The cost of screening per CF birth voluntarily averted was estimated to be
      $1,320,000-$1,400,000. However, the lifetime medical cost of the care of a CF
      child in today's dollars was estimated to be slightly>$1,000,000. Therefore,
      despite both the high cost of carrier testing and the relative infrequency of CF
      conceptions in the general population, the averted medical-care cost resulting
      from choices freely made are estimated to offset approximately 74%-78% of the
      costs of a screening program. At present, if it is assumed that a pregnancy
      terminated because of CF is replaced, the marginal cost for prenatal CF carrier
      screening is estimated to be $8,290 per quality-adjusted life-year. This value
      compares favorably with that of many accepted medical services. The cost of
      prenatal CF carrier screening could fall to equal the averted costs of CF patient
      care if the cost of carrier testing were to fall to $100.

PMID- 9758602
TI  - Do human chromosomal bands 16p13 and 22q11-13 share ancestral origins?

PMID- 9758603
TI  - Partial triplication of mtDNA in maternally transmitted diabetes mellitus and
      deafness.

PMID- 9758604
TI  - Support for a chromosome 18p locus conferring susceptibility to functional
      psychoses in families with schizophrenia, by association and linkage analysis.
AB  - The action of antipsychotic drugs on dopamine receptors suggests that
      dopaminergic signal transmission may play a role in the development of
      schizophrenia. We tested eight candidate genes (coding for dopamine receptors,
      the dopamine transporter, and G-proteins) in 59 families from Germany and Israel,
      for association. A P value of .00055 (.0044 when corrected for the no. of markers
      tested) was obtained for the intronic CA-repeat marker G-olfalpha on chromosome
      18p. The value decreased to .000088 (.0007) when nine sibs with recurrent
      unipolar depressive disorder were included. Linkage analysis using SSLP markers
      densely spaced around G-olfalpha yielded a maximum two-point LOD score of 3.1 for
      a marker 0.5 cM distal to G-olfalpha. Multipoint analysis under the assumption of
      heterogeneity supported this linkage-whether the affected pheotype was defined
      narrowly or broadly-as did nonparametric linkage (NPL). In 12 families with
      exclusively maternal transmission of the disease, the NPL value also supported
      linkage to this marker. In order to test for association/linkage disequilibrium
      in the presence of linkage, the sample was restricted to independent offspring.
      When this sample was combined with 65 additional simplex families (each of them
      comprising one schizophrenic offspring and his or her parents), the 124-bp allele
      of G-olfalpha was transmitted 47 times and was not transmitted 21 times (P=.009).
      These results suggest the existence, on chromosome 18p, of a potential
      susceptibility locus for functional psychoses.

PMID- 9758605
TI  - Autosomal dominant nocturnal frontal-lobe epilepsy: genetic heterogeneity and
      evidence for a second locus at 15q24.
AB  - Autosomal dominant nocturnal frontal-lobe epilepsy (ADNFLE) is a recently
      identified partial epilepsy in which two different mutations have been described
      in the alpha4 subunit of the neuronal nicotinic acetylcholine receptor (CHRNA4).
      An additional seven families are presented in which ADNFLE is unlinked to the
      CHRNA4 region on chromosome 20q13.2. Seven additional sporadic cases showed no
      evidence of defective CHRNA4. One of the families showed evidence of linkage to
      15q24, close to the CHRNA3/CHRNA5/CHRNB4 cluster (maximum LOD score of 3.01 with
      D15S152). Recombination between ADNFLE and CHRNA4, linkage to 15q24 in one
      family, and exclusion from 15q24 and 20q13.2 in others demonstrate genetic
      heterogeneity with at least three different genes for ADNFLE. The CHRNA4 gene and
      the two known CHRNA4 mutations are responsible for only a minority of ADNFLE.
      Although the ADNFLE phenotype is clinically homogeneous, there appear to be a
      variety of molecular defects responsible for this disorder, which will provide a
      challenge to the understanding of the basic mechanism of epileptogenesis.

PMID- 9758606
TI  - Missense and nonsense mutations in the lysosomal alpha-mannosidase gene (MANB) in
      severe and mild forms of alpha-mannosidosis.
AB  - alpha-Mannosidosis is an autosomal recessive lysosomal-storage disorder caused by
      a deficiency of lysosomal alpha-mannosidase activity. This disease shows a wide
      range of clinical phenotypes, from a severe, infantile form (type I), which is
      fatal at <3-8 years of age, to a less severe, late-onset form (type II), which
      ultimately may involve hearing loss, coarse face, mental retardation, and
      hepatosplenomegaly. To elucidate the molecular mechanism underlying this disease
      in both types of patients, we have used PCR, followed by either SSCP analysis or
      direct sequencing, to analyze the 24 exons and intron/exon boundaries of the
      alpha-mannosidase gene (MANB) from five patients. Two amino acid substitutions
      H72L and R750W, in exons 2 and 18, respectively-and two nonsense mutations-Q639X
      and R760X, in exons 15 and 19, respectively-were identified in four type II
      patients. One amino acid substitution, P356R, was identified in exon 8 from a
      type I patient. This patient and three of the type II patients were homozygous
      for their mutations (H72L, P356R, R750W, and R760X) and one type II patient was
      heterozygous for the Q639X and R750W mutations. Transfection experiments of COS 7
      cells, using the alpha-mannosidase cDNA containing one of the missense mutations
      H72L, P356R, or R750W-revealed that each of these mutations dramatically reduces
      the enzymatic activity of alpha-mannosidase. These data demonstrate that widely
      heterogeneous missense or nonsense mutations of the MANB gene are the molecular
      basis underlying alpha-mannosidosis.

PMID- 9758608
TI  - Maternal uniparental disomy of chromosome 1 with no apparent phenotypic effects.

PMID- 9758609
TI  - Reply to Inglehearn.

PMID- 9758610
TI  - On the probability of Neanderthal ancestry.

PMID- 9758614
TI  - Allele identical by descent sharing at any point of a chromosome of a sib pair.

PMID- 9758613
TI  - How sib pairs reveal linkage.

PMID- 9758612
TI  - Adenosine deaminase deficiency: genotype-phenotype correlations based on
      expressed activity of 29 mutant alleles.
AB  - Adenosine deaminase (ADA) deficiency causes lymphopenia and immunodeficiency due
      to toxic effects of its substrates. Most patients are infants with severe
      combined immunodeficiency disease (SCID), but others are diagnosed later in
      childhood (delayed onset) or as adults (late onset); healthy individuals with
      "partial" ADA deficiency have been identified. More than 50 ADA mutations are
      known; most patients are heteroallelic, and most alleles are rare. To analyze the
      relationship of genotype to phenotype, we quantitated the expression of 29 amino
      acid sequence-altering alleles in the ADA-deleted Escherichia coli strain SO3834.
      Expressed ADA activity of wild-type and mutant alleles ranged over five orders of
      magnitude. The 26 disease-associated alleles expressed 0.001%-0.6% of wild-type
      activity, versus 5%-28% for 3 alleles from "partials." We related these data to
      the clinical phenotypes and erythrocyte deoxyadenosine nucleotide (dAXP) levels
      of 52 patients (49 immunodeficient and 3 with partial deficiency) who had 43
      genotypes derived from 42 different mutations, including 28 of the expressed
      alleles. We reduced this complexity to 13 "genotype categories," ranked according
      to the potential of their constituent alleles to provide ADA activity. Of 31 SCID
      patients, 28 fell into 3 genotype categories that could express <=0.05% of wild
      type ADA activity. Only 2 of 21 patients with delayed, late-onset, or partial
      phenotypes had one of these "severe" genotypes. Among 37 patients for whom
      pretreatment metabolic data were available, we found a strong inverse correlation
      between red-cell dAXP level and total ADA activity expressed by each patient's
      alleles in SO3834. Our system provides a quantitative framework and ranking
      system for relating genotype to phenotype.

PMID- 9758611
TI  - Familial eosinophilia maps to the cytokine gene cluster on human chromosomal
      region 5q31-q33.
AB  - Familial eosinophilia (FE) is an autosomal dominant disorder characterized by
      peripheral hypereosinophilia of unidentifiable cause with or without other organ
      involvement. To localize the gene for FE, we performed a genomewide search in a
      large U.S. kindred, using 312 different polymorphic markers. Seventeen affected
      subjects, 28 unaffected bloodline relatives, and 8 spouses were genotyped. The
      initial linkage results from the genome scan provided evidence for linkage on
      chromosome 5q31-q33. Additional genotyping of genetic markers located in this
      specific region demonstrated significant evidence that the FE locus is situated
      between the chromosome 5q markers D5S642 and D5S816 (multipoint LOD score of
      6.49). Notably, this region contains the cytokine gene cluster, which includes
      three genes-namely, those for interleukin (IL)-3, IL-5, and
      granulocyte/macrophage colony-stimulating factor (GM-CSF)-whose products play
      important roles in the development and proliferation of eosinophils. These three
      cytokine genes were screened for potential disease-specific mutations by
      resequencing of a subgroup of individuals from the present kindred. No functional
      sequence polymorphisms were found within the promoter, the exons, or the introns
      of any of these genes or within the IL-3/GM-CSF enhancer, suggesting that the
      primary defect in FE is not caused by a mutation in any one of these genes but,
      rather, is caused by another gene in the area.

PMID- 9758615
TI  - Ascertainment corrections based on smaller family units.
AB  - Ascertainment concerns the manner by which families are selected for genetic
      analysis and how to correct for it in likelihood models. Because such families
      are often neither drawn at random nor selected according to well-defined rules,
      the problem of ascertainment correction in the genetic analysis of family data
      has proved durable. This paper undertakes a systematic study of ascertainment
      corrections in terms of smaller distinct units, which will usually be sibships,
      nuclear families, or small pedigrees. Three principal results are presented. The
      first is that ascertainment corrections in likelihood models for family data can
      be made in terms of smaller units, without breaking up the pedigree. The second
      is that the appropriate correction for single ascertainment in a unit is the
      reciprocal of the sum of the marginal probabilities of all the persons relevant
      to its ascertainment, as if affected. The third result is a generalization of the
      single ascertainment-correction formula to k-plex ascertainment, in which each
      unit has k or more affecteds. The correction is the reciprocal of the sum of the
      joint probabilities of all distinct sets of k persons in the unit, as if they
      were all affected. In extended families, two additional ascertainment schemes
      will be considered and explicit formulas will be presented. One of these schemes
      is "uniform-proband-status ascertainment," in which nonmembers of a given unit
      have the same chance as members to become probands if they are affected; the
      other scheme is the "inverse law of ascertainment," in which the chance that
      nonmembers of a unit will become probands for that unit decreases with degree of
      relationship. Several specific recommendations are made for further study.

PMID- 9758616
TI  - Chromosome 21 disomy in the spermatozoa of the fathers of children with trisomy
      21, in a population with a high prevalence of Down syndrome: increased incidence
      in cases of paternal origin.
AB  - Between April 1991 and December 1994, epidemiological studies detected a
      population with a high prevalence of Down syndrome in El Valles, Spain. Parallel
      double studies were carried out to determine the parental and the meiotic origins
      of the trisomy 21, by use of DNA polymorphisms, and to establish the incidence of
      disomy 21 in the spermatozoa of the fathers of affected children, by use of
      multicolor FISH. Results show that the overall incidence of chromosome 21 disomy
      in the fathers of affected children was not significantly different from that in
      the control population (0.31% vs. 0.37%). However, analysis of individual data
      demonstrates that two cases (DP-4 and DP-5) with significant increases of disomy
      21 (0. 75% and 0.78% vs. 0.37%) correspond to the fathers of the two individuals
      with Down syndrome of paternal origin. DP-5 also had a significant increase of
      sex-chromosome disomies (0.69% vs. 0.37%) and of diploid spermatozoa (1.13% vs.
      0.24%).

PMID- 9758618
TI  - Attitudes of deaf adults toward genetic testing for hereditary deafness.
AB  - Recent advances within molecular genetics to identify the genes for deafness mean
      that it is now possible for genetic-counseling services to offer genetic testing
      for deafness to certain families. The purpose of this study is to document the
      attitudes of deaf adults toward genetic testing for deafness. A structured, self
      completion questionnaire was given to delegates at an international conference on
      the "Deaf Nation," held at the University of Central Lancashire in 1997. The
      conference was aimed at well-educated people, with an emphasis on Deaf culture
      issues. Eighty-seven deaf delegates from the United Kingdom returned completed
      questionnaires. The questionnaire had been designed to quantitatively assess
      attitudes toward genetics, interest in prenatal diagnosis (PND) for deafness, and
      preference for having deaf or hearing children. The results from this study
      provide evidence of a predominantly negative attitude toward genetics and its
      impact on deaf people, in a population for whom genetic-counseling services are
      relevant. Fifty-five percent of the sample thought that genetic testing would do
      more harm than good, 46% thought that its potential use devalued deaf people, and
      49% were concerned about new discoveries in genetics. When asked about testing in
      pregnancy, 16% of participants said that they would consider having PND, and, of
      these, 29% said that they would prefer to have deaf children. Geneticists need to
      appreciate that some deaf persons may prefer to have deaf children and may
      consider the use of genetic technology to achieve this. Any genetic-counseling
      service set up for families with deafness can only be effective and appropriate
      if clinicians and counselors take into consideration the beliefs and values of
      the deaf community at large.

PMID- 9758617
TI  - Mutation in the human acetylcholinesterase-associated collagen gene, COLQ, is
      responsible for congenital myasthenic syndrome with end-plate
      acetylcholinesterase deficiency (Type Ic).
AB  - Congenital myasthenic syndrome (CMS) with end-plate acetylcholinesterase (AChE)
      deficiency is a rare autosomal recessive disease, recently classified as CMS type
      Ic (CMS-Ic). It is characterized by onset in childhood, generalized weakness
      increased by exertion, refractoriness to anticholinesterase drugs, and
      morphological abnormalities of the neuromuscular junctions (NMJs). The collagen
      tailed form of AChE, which is normally concentrated at NMJs, is composed of
      catalytic tetramers associated with a specific collagen, COLQ. In CMS-Ic
      patients, these collagen-tailed forms are often absent. We studied a large family
      comprising 11 siblings, 6 of whom are affected by a mild form of CMS-Ic. The
      muscles of the patients contained collagen-tailed AChE. We first excluded the
      ACHE gene (7q22) as potential culprit, by linkage analysis; then we mapped COLQ
      to chromosome 3p24.2. By analyzing 3p24.2 markers located close to the gene, we
      found that the six affected patients were homozygous for an interval of 14 cM
      between D3S1597 and D3S2338. We determined the COLQ coding sequence and found
      that the patients present a homozygous missense mutation, Y431S, in the conserved
      C-terminal domain of COLQ. This mutation is thought to disturb the attachment of
      collagen-tailed AChE to the NMJ, thus constituting the first genetic defect
      causing CMS-Ic.

PMID- 9758620
TI  - A gene for Meckel syndrome maps to chromosome 11q13.
AB  - Meckel syndrome (MKS) is a rare autosomal recessive lethal condition of unknown
      origin, characterized by (i) an occipital meningo-encephalocele with (ii)
      enlarged kidneys, with multicystic dysplasia and fibrotic changes in the portal
      area of the liver and with ductal proliferation, and (iii) postaxial polydactyly.
      A gene responsible for MKS in Finland has been mapped to chromosome 17q21-q24.
      Studying a subset of Middle Eastern and northern African MKS families, we have
      recently excluded the chromosome 17 region and have suggested a genetic
      heterogeneity. In the present study, we report on the mapping of a second MKS
      locus (MKS2) to chromosome 11q13, by homozygosity mapping in seven families that
      do not show linkage to chromosome 17q21-q24 (maximum LOD score 4.41 at
      recombination fraction .01). Most interestingly, the affected fetuses of southern
      Tunisian ancestry shared a particular haplotype at loci D11S911 and D11S906,
      suggesting that a founder effect is involved. Our observation gives support to
      the clinical and genetic heterogeneity of MKS.

PMID- 9758619
TI  - An autosomal genomic scan for loci linked to type II diabetes mellitus and body
      mass index in Pima Indians.
AB  - Genetic factors influence the development of type II diabetes mellitus, but
      genetic loci for the most common forms of diabetes have not been identified. A
      genomic scan was conducted to identify loci linked to diabetes and body-mass
      index (BMI) in Pima Indians, a Native American population with a high prevalence
      of type II diabetes. Among 264 nuclear families containing 966 siblings, 516
      autosomal markers with a median distance between adjacent markers of 6.4 cM were
      genotyped. Variance-components methods were used to test for linkage with an age
      adjusted diabetes score and with BMI. In multipoint analyses, the strongest
      evidence for linkage with age-adjusted diabetes (LOD = 1.7) was on chromosome
      11q, in the region that was also linked most strongly with BMI (LOD = 3.6).
      Bivariate linkage analyses strongly rejected both the null hypothesis of no
      linkage with either trait and the null hypothesis of no contribution of the locus
      to the covariation among the two traits. Sib-pair analyses suggest additional
      potential diabetes-susceptibility loci on chromosomes 1q and 7q.

PMID- 9758621
TI  - Analysis of mutations in the XPD gene in Italian patients with
      trichothiodystrophy: site of mutation correlates with repair deficiency, but gene
      dosage appears to determine clinical severity.
AB  - Xeroderma pigmentosum (XP) complementation group D is a heterogeneous group,
      containing patients with XP alone, rare cases with both XP and Cockayne syndrome,
      and patients with trichothiodystrophy (TTD). TTD is a rare autosomal recessive
      multisystem disorder associated, in many patients, with a defect in nucleotide
      excision repair; but in contrast to XP patients, TTD patients are not cancer
      prone. In most of the repair-deficient TTD patients, the defect has been assigned
      to the XPD gene. The XPD gene product is a subunit of transcription factor TFIIH,
      which is involved in both DNA repair and transcription. We have determined the
      mutations and the pattern of inheritance of the XPD alleles in the 11 cases
      identified in Italy so far, in which the hair abnormalities diagnostic for TTD
      are associated with different disease severity but similar cellular
      photosensitivity. We have identified eight causative mutations, of which four
      have not been described before, either in TTD or XP cases, supporting the
      hypothesis that the mutations responsible for TTD are different from those found
      in other pathological phenotypes. Arg112his was the most common alteration in the
      Italian patients, of whom five were homozygotes and two were heterozygotes, for
      this mutation. The presence of a specifically mutated XPD allele, irrespective of
      its homozygous, hemizygous, or heterozygous condition, was always associated with
      the same degree of cellular UV hypersensitivity. Surprisingly, however, the
      severity of the clinical symptoms did not correlate with the magnitude of the DNA
      repair defect. The most severe clinical features were found in patients who
      appear to be functionally hemizygous for the mutated allele.

PMID- 9758622
TI  - Assignment of the locus for congenital lactase deficiency to 2q21, in the
      vicinity of but separate from the lactase-phlorizin hydrolase gene.
AB  - Congenital lactase deficiency (CLD) is an autosomal recessive, gastrointestinal
      disorder characterized by watery diarrhea starting during the first 1-10 d of
      life, in infants fed lactose-containing milks. Since 1966, 42 patients have been
      diagnosed in Finland. CLD is the most severe form of lactase deficiency, with an
      almost total lack of lactase-phlorizin hydrolase (LPH) activity on jejunal
      biopsy. In adult-type hypolactasia, the most common genetic enzyme deficiency in
      humans, this enzyme activity is reduced to 5%-10%. Although the activity of
      intestinal LPH has been found to be greatly reduced in both forms, the molecular
      pathogenesis of lactase deficiencies is unknown. On the basis of the initial
      candidate-gene approach, we assigned the CLD locus to an 8-cM interval on
      chromosome 2q21 in 19 Finnish families. At the closest marker locus, a specific
      allele 2 was present in 92% of disease alleles. On the basis of a genealogical
      study, the CLD mutation was found to be enriched in sparsely populated eastern
      and northern Finland, because of a founder effect. The results of both the
      genealogical study and the haplotype analysis indicate that one major mutation in
      a novel gene causes CLD in the Finnish population. Consequently, the critical
      region could be restricted further, to an approximately 350-kb interval, by
      ancient-haplotype and linkage-disequilibrium analyses. Surprisingly, the LPH gene
      was shown to lie outside the critical CLD region, excluding it as a causative
      gene for CLD. The LPH locus was found to reside >2 Mb from the critical CLD
      region.

PMID- 9758623
TI  - Methylation levels at selected CpG sites in the factor VIII and FGFR3 genes, in
      mature female and male germ cells: implications for male-driven evolution.
AB  - Transitional mutations at CpG dinucleotides account for approximately a third of
      all point mutations. These mutations probably arise through spontaneous
      deamination of 5-methylcytosine. Studies of CpG mutation rates in disease-linked
      genes, such as factor VIII and FGFR3, have indicated that they more frequently
      originate in male than in female germ cells. It has been speculated that these
      sex-biased mutation rates might be a consequence of sex-specific methylation
      differences between the female and the male germ lines. Using the bisulfite-based
      genomic-sequencing method, we investigated the methylation status of the human
      factor VIII and FGFR3 genes in mature male and female germ cells. With the
      exception of a single CpG, both genes were found to be equally and highly
      methylated in oocytes and spermatocytes. Whereas these observations strongly
      support the notion that DNA methylation is the major determining factor for
      recurrent CpG germ-line mutations in patients with hemophilia and achondroplasia,
      the higher mutation rate in the male germ line is apparently not a simple
      reflection of sex-specific methylation differences.

PMID- 9758624
TI  - Childhood absence epilepsy with tonic-clonic seizures and electroencephalogram 3
      4-Hz spike and multispike-slow wave complexes: linkage to chromosome 8q24.
AB  - Childhood absence epilepsy (CAE), a common form of idiopathic generalized
      epilepsy, accounts for 5%-15% of childhood epilepsies. To map the chromosomal
      locus of persisting CAE, we studied the clinical and electroencephalographic
      traits of 78 members of a five-generation family from Bombay, India. The model
      free affected-pedigree member method was used during initial screening with
      chromosome 6p, 8q, and 1p microsatellites, and only individuals with absence
      seizures and/or electroencephalogram 3-4-Hz spike- and multispike-slow wave
      complexes were considered to be affected. Significant P values of .00000-.02 for
      several markers on 8q were obtained. Two-point linkage analysis, assuming
      autosomal dominant inheritance with 50% penetrance, yielded a maximum LOD score
      (Zmax) of 3.6 for D8S502. No other locus in the genome achieved a significant
      Zmax. For five smaller multiplex families, summed Zmax was 2.4 for D8S537 and 1.7
      for D8S1761. Haplotypes composed of the same 8q24 microsatellites segregated with
      affected members of the large family from India and with all five smaller
      families. Recombinations positioned the CAE gene in a 3.2-cM interval.

PMID- 9758625
TI  - Close associations between prevalences of dominantly inherited spinocerebellar
      ataxias with CAG-repeat expansions and frequencies of large normal CAG alleles in
      Japanese and Caucasian populations.
AB  - To test the hypothesis that the frequencies of normal alleles (ANs) with a
      relatively large number of CAG repeats (large ANs) are related to the prevalences
      of the dominant spinocerebellar ataxias (SCAs)-SCA types 1, 2, 3 (Machado-Joseph
      disease), 6, and dentatorubral-pallidoluysian atrophy (DRPLA)-we investigated the
      relative prevalences of these diseases in 202 Japanese and 177 Caucasian families
      and distributions of the number of CAG repeats of ANs at these disease loci in
      normal individuals in each population. The relative prevalences of SCA1 and SCA2
      were significantly higher in Caucasian pedigrees (15% and 14%, respectively) than
      in Japanese pedigrees (3% and 5%, respectively), corresponding to the observation
      that the frequencies of large ANs of SCA1 (alleles >30 repeats) and of SCA2
      (alleles >22 repeats) were significantly higher in Caucasians than in Japanese.
      The relative prevalences of MJD/SCA3, SCA6, and DRPLA were significantly higher
      in Japanese pedigrees (43%, 11%, and 20%, respectively) than in Caucasian
      pedigrees (30%, 5%, and 0%, respectively), corresponding to the observation that
      the frequencies of large ANs of MJD/SCA3 (>27 repeats), SCA6 (>13 repeats), and
      DRPLA (>17 repeats) were significantly higher in Japanese than in Caucasians. The
      close correlations of the relative prevalences of the dominant SCAs with the
      distributions of large ANs strongly support the assumption that large ANs
      contribute to generation of expanded alleles (AEs) and the relative prevalences
      of the dominant SCAs.

PMID- 9758626
TI  - A gene on chromosome 11q23 coding for a putative glucose- 6-phosphate translocase
      is mutated in glycogen-storage disease types Ib and Ic.
AB  - Glycogen-storage diseases type I (GSD type I) are due to a deficiency in glucose
      6-phosphatase, an enzymatic system present in the endoplasmic reticulum that
      plays a crucial role in blood glucose homeostasis. Unlike GSD type Ia, types Ib
      and Ic are not due to mutations in the phosphohydrolase gene and are clinically
      characterized by the presence of associated neutropenia and neutrophil
      dysfunction. Biochemical evidence indicates the presence of a defect in glucose-6
      phosphate (GSD type Ib) or inorganic phosphate (Pi) (GSD type Ic) transport in
      the microsomes. We have recently cloned a cDNA encoding a putative glucose-6
      phosphate translocase. We have now localized the corresponding gene on chromosome
      11q23, the region where GSD types Ib and Ic have been mapped. Using SSCP analysis
      and sequencing, we have screened this gene, for mutations in genomic DNA, from
      patients from 22 different families who have GSD types Ib and Ic. Of 20 mutations
      found, 11 result in truncated proteins that are probably nonfunctional. Most
      other mutations result in substitutions of conserved or semiconserved residues.
      The two most common mutations (Gly339Cys and 1211-1212 delCT) together constitute
      approximately 40% of the disease alleles. The fact that the same mutations are
      found in GSD types Ib and Ic could indicate either that Pi and glucose-6
      phosphate are transported in microsomes by the same transporter or that the
      biochemical assays used to differentiate Pi and glucose-6-phosphate transport
      defects are not reliable.

PMID- 9758627
TI  - A missense mutation in the zinc-finger domain of the human hairless gene
      underlies congenital atrichia in a family of Irish travellers.
AB  - Congenital atrichia is a rare, recessively inherited form of hair loss affecting
      both males and females and is characterized by a complete absence of hair
      follicles. Recently, a mutation in the human hairless gene was implicated in the
      pathogenesis of congenital atrichia. The human hairless gene encodes a putative
      single zinc-finger transcription-factor protein with restricted expression in
      brain and skin, which is believed to regulate catagen remodeling in the hair
      cycle. In this study, we report the identification of a missense mutation in the
      zinc-finger domain of the hairless gene in a large inbred family of Irish
      Travellers with congenital atrichia. The mutated arginine residue is conserved
      among human, mouse, and rat, suggesting that it is of significant importance to
      the function of the zinc-finger domain.

PMID- 9758629
TI  - Homozygosity mapping of a gene responsible for gelatinous drop-like corneal
      dystrophy to chromosome 1p.
AB  - Gelatinous drop-like corneal dystrophy (GDLD) is a rare autosomal recessive
      disorder characterized clinically by grayish corneal deposits of amyloid and by
      severely impaired visual acuity. Most patients require corneal transplantation.
      To localize a gene responsible for GDLD, we performed linkage analysis of 10
      consanguineous Japanese families with a total of 13 affected members.
      Homozygosity mapping provided a maximum LOD score of 9.80 at the D1S2741 marker
      locus on the short arm of chromosome 1. Haplotype analysis further defined the
      disease locus within a region of approximately 2.6 cM between D1S2890 and
      D1S2801.

PMID- 9758628
TI  - Deletions in HOXD13 segregate with an identical, novel foot malformation in two
      unrelated families.
AB  - Synpolydactyly (SPD) is a dominantly inherited congenital limb malformation
      consisting of 3/4 syndactyly in the hands and 4/5 syndactyly in the feet, with
      digit duplication in the syndactylous web. The condition recently has been found
      to result from different-sized expansions of an amino-terminal polyalanine tract
      in HOXD13. We report a novel type of mutation in HOXD13, associated in some cases
      with features of classic SPD and in all cases with a novel foot phenotype. In two
      unrelated families, each with a different intragenic deletion in HOXD13, all
      mutation carriers have a rudimentary extra digit between the first and second
      metatarsals and often between the fourth and fifth metatarsals as well. This
      phenotype has not been reported in any mice with genetic modifications of the
      HoxD gene cluster. The two different deletions affect the first exon and the
      homeobox, respectively, in each case producing frameshifts followed by a long
      stretch of novel sequence and a premature stop codon. Although the affected genes
      may encode proteins that exert a dominant negative or novel effect, they are most
      likely to act as null alleles. Either possibility has interesting implications
      for the role of HOXD13 in human autopod development.

PMID- 9758630
TI  - Linkage disequilibrium mapping of the gene for Margarita Island ectodermal
      dysplasia (ED4) to 11q23.
AB  - Margarita Island ectodermal dysplasia (ED4) is an autosomal recessive disorder
      characterized by unusual facies, dental anomalies, hypotrichosis, palmoplantar
      hyperkeratosis and onychodysplasia, syndactyly, and cleft lip/cleft palate. We
      have used an affected-only DNA-pooling strategy to carry out linkage
      disequilibrium mapping of the ED4 gene to 11q23. Haplotype analysis of four
      complex Margarita Island ED4 families localized the ED4 gene to an approximately
      1-2-Mb interval spanned by just two YACs.

PMID- 9758631
TI  - Methods of linkage analysis--and the assumptions underlying them [see comment].

PMID- 9758632
TI  - Uniparental disomies in unselected populations.

PMID- 9758633
TI  - Complex segregation analyses: uses and limitations.

PMID- 9758634
TI  - Bayesian linkage analysis, or: how I learned to stop worrying and love the
      posterior probability of linkage.

PMID- 9758635
TI  - Transmission disequilibrium, family controls, and great expectations.

PMID- 9758636
TI  - A model of elegance.

PMID- 9758637
TI  - 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors increase fibrinolytic
      activity in rat aortic endothelial cells. Role of geranylgeranylation and Rho
      proteins.
AB  - 3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (HRIs) have
      been recently shown to prevent atherosclerosis progression. Clinical benefit
      results from combined actions on various components of the atherosclerotic
      lesion. This study was designed to identify the effects of HRI on one of these
      components, the endothelial fibrinolytic system. Aortas isolated from rats
      treated for 2 days with lovastatin (4 mg/kg body wt per day) showed a 3-fold
      increase in tissue plasminogen activator (tPA) activity. In a rat aortic
      endothelial cell line (SVARECs) and in human nontransformed endothelial cells
      (HUVECs), HRI induced an increase in tPA activity and antigen in a time- and
      concentration-dependent manner. In SVARECs, the maximal response was observed
      when cells were incubated for 48 hours with 50 micromol/L HRI. An increase of tPA
      mRNA was also in evidence. In contrast, HRI inhibited plasminogen activator
      inhibitor-1 activity and mRNA. The effects of HRI were reversed by mevalonate and
      geranylgeranyl pyrophosphate, but not by LDL cholesterol and farnesyl
      pyrophosphate, and were not induced by alpha-hydroxyfarnesyl phosphonic acid, an
      inhibitor of protein farnesyl transferase. C3 exoenzyme, an inhibitor of the
      geranylgeranylated-activated Rho protein, reproduced the effect of lovastatin on
      tPA and plasminogen activator inhibitor-1 activity and blocked its reversal by
      geranylgeranyl pyrophosphate. The effect of HRI was associated with a disruption
      of cellular actin filaments without modification of microtubules. A disrupter of
      actin filaments, cytochalasin D, induced the same effect as lovastatin on tPA,
      whereas a disrupter of microtubules, nocodazole, did not. In conclusion, HRI can
      modify the fibrinolytic potential of endothelial cells, likely via inhibition of
      geranylgeranylated Rho protein and disruption of the actin filaments. The
      resulting increase of fibrinolytic activity of endothelial cells may contribute
      to the beneficial effects of HRI in the progression of atherosclerosis.

PMID- 9758638
TI  - Transgenic mice with increased copper/zinc-superoxide dismutase activity are
      resistant to hepatic leukostasis and capillary no-reflow after gut
      ischemia/reperfusion.
AB  - The objectives of this study were to (1) determine whether transgenic (Tg) mice
      overexpressing copper/zinc-superoxide dismutase (CuZn-SOD) are protected from the
      deleterious effects of gut ischemia/reperfusion (I/R) and (2) compare the
      effectiveness of Tg SOD overexpression in attenuating I/R injury to
      intravascularly administered CuZn-SOD or manganese (Mn)-SOD. The accumulation of
      fluorescently labeled leukocytes and number of nonperfused sinusoids were
      monitored by intravital microscopy in livers of wild-type mice (C57BL/6), CuZn
      SOD Tg mice, and wild-type mice receiving either CuZn-SOD or Mn-SOD. All
      parameters were measured for 1 hour after release of the occluded (for 15
      minutes) superior mesenteric artery. Gut I/R in wild-type mice led to an
      increased number of stationary leukocytes, while reducing the number of perfused
      sinusoids (capillary no-reflow). All of these responses were significantly
      blunted in CuZn-SOD Tg mice, with a corresponding attenuation of liver enzyme
      release into plasma. Exogenously administered SOD had little or no effect on gut
      I/R-induced leukostasis or capillary no-reflow in the liver. These observations
      suggest a role for superoxide in gut I/R-induced leukostasis and hypoxic stress
      in the liver. Furthermore, the findings suggest that cellular localization of SOD
      activity is an important determinant of the protective actions of this enzyme in
      experimental models of I/R injury.

PMID- 9758639
TI  - Increased expression of Axl tyrosine kinase after vascular injury and regulation
      by G protein-coupled receptor agonists in rats.
AB  - Axl is a receptor tyrosine kinase originally identified as a transforming gene
      product in human myeloid leukemia cells. Cultured rat vascular smooth muscle
      cells also express Axl, where it has been proposed that Axl may play a role in
      cell proliferation. In the current study, we tested the hypotheses that Axl
      expression would parallel neointima formation in balloon-injured rat carotid, and
      that Axl expression would be regulated by growth factors present at sites of
      vascular injury. Ribonuclease protection assay showed dynamic increases in Axl
      mRNA in vessels, with peak expression 7 and 14 days after injury.
      Immunohistochemical analysis confirmed these results and demonstrated that Axl
      protein expression was localized primarily to cells of the neointima after
      injury. Northern blot analysis indicated increased mRNA expression for the
      secreted Axl ligand, Gas6, in injured carotids, with a time course paralleling
      that of Axl upregulation. Axl and Gas6 expression were temporally correlated with
      neointima formation, suggesting a role for Axl signaling in this process. Other
      studies, performed in cultured rat vascular smooth muscle cells, revealed
      positive regulation of Axl mRNA expression by thrombin or angiotensin II but not
      by basic fibroblast growth factor, platelet-derived growth factor-BB, or
      transforming growth factor-ss1. Western blot analysis confirmed these results,
      showing that Axl protein expression was specifically increased by thrombin or
      angiotensin II. Our results implicate Axl as a potential mediator of vascular
      smooth muscle migration and proliferation caused by vascular injury and G protein
      coupled receptor agonists.

PMID- 9758640
TI  - Animal model that mimics atherosclerotic plaque rupture.
AB  - Atherosclerotic plaque rupture is the main cause of coronary thrombosis and
      myocardial infarcts. Currently, there is no animal model of plaque disruption. We
      have developed a rabbit model in which an atherosclerotic plaque can be ruptured
      at will after an inflatable balloon becomes embedded into the plaque.
      Furthermore, the pressure needed to inflate the plaque-covered balloon may be an
      index of overall plaque mechanical strength. The thoracic aorta of
      hypercholesterolemic rabbits underwent mechanical removal of endothelial cells,
      and then a specially designed balloon catheter was introduced into the lumen of
      the thoracic aorta. As early as 1 month after catheter placement, atherosclerotic
      plaque formed around the indwelling balloon. The plaques were reminiscent of
      human atherosclerotic lesions, in terms of cellular composition, patterns of
      lipid accumulation, and growth characteristics. Intraplaque balloons were
      inflated both ex vivo and in vivo, leading to plaque fissuring. The ex vivo
      strategy is designed to measure the mechanical strength of the surrounding
      plaque, while the in vivo scenario permits an analysis of the plaque rupture
      consequences, eg, thrombosis. In addition, our model allows local delivery of
      various substances into the plaque. The model can be used to study the
      pathogenesis of plaque instability and to design plaque stabilization therapy.

PMID- 9758641
TI  - Retinal arterial tone is controlled by a retinal-derived relaxing factor.
AB  - The present study provides evidence that retinal tissue may profoundly influence
      the retinal arterial smooth muscle cell tone by releasing an unknown retinal
      relaxing factor. Isolated bovine retinal arteries with and without adhering
      retinal tissue were mounted in a wire myograph for isometric tension recordings.
      The maximal contraction induced by prostaglandin F2alpha was 0.95+/-0.7 mN (n=6)
      in the presence and 5.15+/-0.76 mN (n=6) in the absence of adhering retinal
      tissue. The contractions induced by U-46619, serotonin, and endothelin-1 were
      similarly blocked in the presence of retinal tissue. The K+ 120 mmol/L-induced
      contraction was not significantly affected (2.8+/-0.7 mN, n=6, in the presence
      and 3. 6+/-0.7 mN, n=6, in the absence of retinal tissue). Placing a piece of
      bovine retinal tissue in the proximity of a contracted (ie, with prostaglandin
      F2alpha) retinal artery induced a complete relaxation of the retinal vessel,
      suggesting the involvement of a diffusible chemical vasorelaxant. Also porcine,
      canine, and ovine retinal tissue completely relaxed the contracted (with
      prostaglandin F2alpha) bovine retinal artery. Other smooth muscle preparations,
      including rat mesenteric and renal arteries and rat main bronchi, also relaxed
      with the application of a piece of bovine retinal tissue. Incubation of bovine
      retinas in a Krebs-Ringer bicarbonate solution yielded a solution that relaxed
      isolated precontracted bovine retinal arteries, confirming the involvement of a
      diffusible chemical messenger. Hexane extraction, heating the solution to 70
      degrees C, or treatment with trypsin did not alter the relaxing properties of the
      incubation solution. The characteristics of the retinal relaxing factor do not
      correspond with those of nitric oxide, prostanoids, adenosine, acetylcholine, or
      any other of the known vasoactive neurotransmitters released from the retina. Our
      results suggest that retinal arterial tone is controlled by a diffusible,
      hydrophilic, and heat-stable relaxing factor that does not correspond with a
      known vasoactive molecule formed within the retina.

PMID- 9758642
TI  - A major role for prostacyclin in nitric oxide-induced ocular vasorelaxation in
      the piglet.
AB  - We studied the mechanisms of retinal and choroidal vasorelaxation elicited by
      nitric oxide (NO) using piglet eyes. The NO donors sodium nitroprusside (SNP) and
      diethylamine-NONOate caused comparable concentration-dependent relaxation that
      was partially (approximately 40%) attenuated by the guanylate cyclase inhibitors
      methylene blue and LY83583 and reduced to a lesser extent (approximately 25%) by
      the inhibitor of cGMP-dependent kinase, KT 5823. In contrast, NO-induced
      dilatation (by NO donors and endogenous NO after stimulation with bradykinin) was
      substantially (approximately 70%) diminished by the KCa channel blockers
      tetraethylammonium (TEA), charybdotoxin, and iberiotoxin; by the cyclooxygenase
      inhibitors indomethacin and ibuprofen; by the prostaglandin I (PGI2) synthase
      inhibitor trans-2-phenyl cyclopropylamine (TPC); and by the removal of
      endothelium; whereas relaxation of endothelium-denuded vasculature to SNP was
      unaltered by indomethacin, TPC, and charybdotoxin but was nearly nullified by
      methylene blue and the Kv channel blocker 4-aminopyridine. NO donors
      significantly increased PGI2 synthesis and the putative PGI2 receptor-coupled
      second messenger cAMP, from ocular vasculature (retinal microvessels and
      choroidal perfusate), and this increase in PGI2 formation was markedly reduced by
      TPC, tetraethylammonium, charybdotoxin, and/or the removal of endothelium, but it
      was only slightly reduced by methylene blue and LY83583. Also, SNP and KCa
      channel openers NS1619 and NS004 caused an increase in PGI2 synthesis in cultured
      endothelial cells, which was virtually abolished by KCa blockers. Finally,
      vasorelaxation to a cGMP analogue, 8-bromo cGMP, and protein kinase G stimulant
      beta-phenyl-1,N2-etheno-8-bromoguanosine 3':5'-cyclic monophosphate was mostly Kv
      dependent and, in contrast to NO, largely unrelated to PGI2 formation. In
      conclusion, data indicate that NO-induced ocular vasorelaxation is partly
      mediated by cGMP through its action on smooth muscle, and more importantly, by
      stimulating PGI2 formation of endothelial origin via a mechanism mostly
      independent of guanylate cyclase, which involves the opening of a KCa channel.

PMID- 9758643
TI  - Endothelial NADPH oxidase as the source of oxidants in lungs exposed to ischemia
      or high K+.
AB  - We have previously demonstrated the generation of reactive oxygen species (ROS)
      in cultured bovine pulmonary artery endothelial cells (BPAECs) and in isolated
      perfused rat lungs exposed to high K+ and during global lung ischemia. The
      present study evaluates the NADPH oxidase pathway as a source of ROS in these
      models. ROS production, detected by oxidation of the fluorophore,
      dichlorodihydrofluorescein, increased 2.5-fold in BPAECs and 6-fold in rat or
      mouse lungs exposed to high (24 mmol/L) K+. ROS generation was markedly inhibited
      by diphenyliodonium, a flavoprotein inhibitor, and by the synthetic peptide PR
      39, an inhibitor of NADPH oxidase assembly, whereas allopurinol had no effect.
      With ischemia (1 hour), ROS generation by rat and mouse lungs increased 7-fold;
      PR-39 showed concentration-dependent inhibition of ROS production, with 50%
      inhibition at 3 micromol/L PR-39. ROS production in lungs exposed to high K+ or
      ischemia was essentially abolished in mice with a "knockout" of gp91(phox), a
      membrane-localized cytochrome component of NADPH oxidase; increased ROS
      production by these lungs after anoxia/reoxygenation was similar to control. PR
      39 also inhibited ischemia and the high K+-mediated increase in lung
      thiobarbituric acid reactive substance. Western blotting of BPAECs and
      immunocytochemistry of BPAECs and rat and mouse lungs showed the presence of
      p47phox, a cytoplasmic component of NADPH oxidase and the putative target for PR
      39 inhibition. In situ fluorescence imaging in the intact lung demonstrated that
      the increased dichlorofluorescein fluorescence in these models of ROS generation
      was localized primarily to the pulmonary endothelium. These studies demonstrate
      that ROS production in lungs exposed to ischemia or high K+ results from assembly
      and activation of a membrane-associated NAPDH oxidase of the pulmonary
      endothelium.

PMID- 9758644
TI  - Infection of human fetal cardiac myocytes by a human immunodeficiency virus-1
      derived vector.
AB  - Cardiomyopathy associated with HIV-1 infection is a well-recognized complication.
      However, it is unknown whether direct cardiomyocyte infection is involved in the
      pathogenesis of the cardiomyopathy. An HIV-1-based lentiviral vector and wild
      type HIV-1 were used to infect human fetal cardiac myocytes in a primary culture.
      Quantitative polymerase chain reaction, viral p24 antigen determination, and
      immunofluorescence were used to detect the synthesis of HIV-1 DNA and proteins
      after the infection. High-efficiency infection occurred using the HIV-1-based
      lentiviral vector, although no infection occurred with the wild-type HIV-1
      strain. Dual-labeling immunofluorescence for HIV-1 proteins and myosin confirmed
      that cardiomyocytes were infected. This in vitro analysis suggests that direct
      myocyte infection with wild-type HIV-1 may not be involved in the pathogenesis of
      HIV-1 cardiomyopathy. However, HIV-1-based vectors may prove useful for ex vivo
      cardiovascular gene therapy.

PMID- 9758645
TI  - Cardiac angiotensin II receptors are upregulated by long-term inhibition of
      nitric oxide synthesis in rats.
AB  - It has been shown that nitric oxide (NO) may regulate angiotensin II (Ang II)
      receptors in vitro. To determine whether the chronic inhibition of NO synthesis
      upregulates cardiac Ang II receptors in a rat model, we evaluated the in vivo
      effect of Nomega-nitro-L-arginine methyl ester (L-NAME) on several Ang II
      receptors and on the expression of AT1 receptor mRNA in heart tissue. The chronic
      administration of L-NAME to normal rats increased the arterial blood pressure.
      The number of AT1 and AT2 receptors was increased, with no change in affinity,
      during the first week of L-NAME administration but returned to control levels
      after 4 weeks of treatment. The AT1 receptor mRNA was changed parallel to AT1
      receptor number. Inflammatory changes (monocyte infiltration and myofibroblast
      formation) in perivascular areas surrounding coronary vessels and myocardial
      interstitial spaces were observed during the first week. The immunohistochemistry
      revealed that myofibroblasts expressed AT1 receptor. AT1 receptor blockade or
      cotreatment with L-arginine, but not cotreatment with hydralazine, prevented the
      L-NAME-induced increase in Ang II receptors and inflammatory changes. In
      conclusion, rat cardiac Ang II receptors are upregulated at an early phase of
      chronic inhibition of NO synthesis. This may contribute to cardiovascular
      inflammatory changes in an early phase and to remodeling at the later phase,
      which occurs after inhibition of NO synthesis.

PMID- 9758646
TI  - Differential activation of cardiac c-jun amino-terminal kinase and extracellular
      signal-regulated kinase in angiotensin II-mediated hypertension.
AB  - Two subgroups of mitogen-activated protein kinases, c-jun NH2-terminal kinase
      (JNK) and extracellular signal-regulated kinase (ERK), are thought to be involved
      in cultured cardiac myocyte hypertrophy and gene expression. To examine the in
      vivo activation of these kinases, we measured cardiac JNK and ERK activities in
      conscious rats subjected to acute or chronic angiotensin II (Ang II) infusion, by
      using in-gel kinase methods. About 50 mm Hg rise in blood pressure by Ang II
      (1000 ng . kg-1 . min-1) infusion caused larger activation of left ventricular
      JNK than ERK, via the AT1 receptor. In spite of short duration (about 30 minutes)
      of maximal blood pressure elevation by Ang II, JNK sustained the peak value (more
      than 5-fold increase) from 15 minutes up to at least 3 hours. Similar activation
      of JNK was seen in the right ventricle. Thus, cardiac JNK activation by Ang II
      seems to be in part mediated by its direct action via the AT1 receptor. The dose
      response relationships for Ang II-induced rises in blood pressure and cardiac JNK
      and ERK activation indicated that cardiac JNK or ERK was not activated by a mild
      increase in blood pressure and that cardiac JNK was activated by Ang II-mediated
      hypertension in a more sensitive manner than ERK. Cardiac hypertrophy, induced by
      chronic Ang II infusion, was preceded by JNK activation without ERK activation.
      Furthermore, gel mobility shift analysis showed that cardiac JNK activation was
      followed by increased activator protein-1 DNA binding activity due to c-Fos and c
      Jun. These results provided the first evidence for the preferential activation of
      cardiac JNK in Ang II-induced hypertension and suggested that JNK might play some
      role in Ang II-induced cardiac hypertrophic response in vivo. However, further
      study is needed to elucidate the role of JNK in cardiac hypertrophy in vivo.

PMID- 9758647
TI  - Adenosine mediates sustained adrenergic desensitization in the rat heart via
      activation of protein kinase C.
AB  - Adenosine attenuates the myocardial metabolic and contractile responses induced
      by ss-adrenergic stimulation. Our study was conducted to investigate the
      longevity of this antiadrenergic action after adenosine exposure. Adenosine (33
      micromol/L) was infused into isolated perfused rat hearts for 1, 5, 30, or 60
      minutes, and the adrenergic responsiveness (AR) to isoproterenol (10(-8) mol/L)
      was determined at the end of each infusion period and during a 45-minute
      adenosine washout period. Interstitial levels of adenosine, as determined from
      epicardial surface transudates, returned to preinfusion levels within 10 minutes
      of washout. The duration of adenosine infusion had no effect on the extent of
      attenuation of AR at the end of the infusion. Whereas AR returned to preadenosine
      levels with washout of shorter adenosine infusions (1 and 5 minutes), there was a
      slow and incomplete recovery of AR after the longer exposures (30 and 60 minutes)
      to adenosine. The magnitude of this persistent antiadrenergic effect (PAE) of
      adenosine at 15 minutes of washout was proportional to the epicardial
      concentration of adenosine during infusion of the nucleoside. Infusion of
      adenosine either with the nonselective adenosine receptor antagonist 8-p
      sulfophenyl theophylline or with the selective A1-receptor antagonist 1,3
      dipropyl, 8-cyclopentylxanthine, abolished the PAE during the washout period. In
      addition, the PAE could be demonstrated only with the selective A1-receptor
      agonist 2-chloro-N6-cyclopentyladenosine and not with the selective A3-receptor
      agonist 4-aminobenzyl-5'-N methylcarboxamido-adenosine. When the protein kinase C
      (PKC) inhibitor chelerythrine was coadministered with adenosine, the PAE of
      adenosine was not apparent during adenosine washout. A 30-minute infusion of
      phenylephrine, an alpha-adrenergic agonist that enhances PKC activity, produced a
      PAE that lasted for up to 30 minutes of washout. This effect was prevented by the
      coinfusion of chelerythrine. Thus, it is concluded that the PAE of adenosine is
      determined by the myocardial concentration of this nucleoside and is manifested
      when myocardial concentrations of adenosine returned to baseline levels.
      Moreover, a 5-minute duration of adenosine exposure is required for the
      expression of the PAE. This latter effect seems to be dependent on adenosine
      induced PKC activation via A1-receptors.

PMID- 9758649
TI  - Introduction 

PMID- 9758648
TI  - Novel vasodilator released by retinal tissue.

PMID- 9758650
TI  - Corneal topography in LASIK.
AB  - Corneal topography plays an important role in laser in situ keratomileusis
      (LASIK). Preoperative screening permits the detection of keratoconus and other
      corneal shape anomalies that may be a contraindication for refractive surgery.
      Monitoring the progress of the surgical outcome with topography is helpful to
      detect postoperative complications such as decentration and clinically
      significant irregular astigmatism. LASIK compares favorably with PRK for the
      treatment of low to moderate myopia in terms of early achievement of refractive
      stability, but induction of modest amounts of irregular astigmatism can be a
      concern.

PMID- 9758651
TI  - Outcomes of spherocylinder treatments in the comprehensive refractive surgery
      LASIK study.
AB  - The CRS LASIK Study is a surgeon-sponsored collaborative project to evaluate
      LASIK outcomes with the Summit and VISX lasers. The current report includes 3
      month outcomes in the first group of patients who underwent spherocylindrical
      corrections of 1 to 10 diopters of myopia and 1 to 4 diopters of astigmatism with
      the Summit Apex Plus and VISX Star lasers. Cohort selection criteria were applied
      to select 911 eyes that underwent surgery between April 1, 1996 and October 1,
      1997 in the range of study. Eyes with preoperative best spectacle-corrected
      visual acuity of worse than 20/40 (0.5) were excluded. Outcomes were stratified
      according to myopic treatment range. One day uncorrected visual acuity was 20/40
      or better in 83% of eyes with both lasers. At 3 months, 20/40 uncorrected acuity
      was found in 93% of Summit and 90% of VISX eyes in the -1.00 to -4.00 D group, in
      88% of Summit and 84% of VISX eyes in the -4.01 to -7.00 D group, and in 67% of
      Summit and 70% of VISX eyes in the -7.01 to -10 D group. Three-month manifest
      refractive outcomes in the -1.00 to -4. 00 D group were within +/- 1 D of target
      in 91% of the Summit eyes, and 89% of the VISX Eyes. In the -4.01 to -7.00 D
      range, 72% of the Summit eyes and 74% of the VISX eyes fell within +/- 1 D, and
      in the -7.01 to -10 D range, the rates were 53% for Summit and 56% for VISX. No
      eyes lost two lines or more acuity with either laser. Three-month visual and
      refractive outcomes in LASIK are comparable with the Summit Apex Plus and VISX
      Star lasers. Loss of BSCVA of two lines or more was not seen. CRS LASIK Study
      protocols are ongoing to provide longer follow-up and to study other refractive
      indications.

PMID- 9758652
TI  - Regression after LASIK for the treatment of myopia: the role of the corneal
      epithelium.
AB  - Factors responsible for postoperative regression are still unknown but
      postoperative epithelial hyperplasia might play an important role. To evaluate
      the role of the corneal epithelium on regression after laser in situ
      keratomileusis (LASIK), the thickness of the epithelium was measured in 18 eyes
      preoperatively and at various postoperative intervals. Measurements of the
      epithelial thickness were taken using a high-frequency (50 MHz) ultrasound device
      and measurements were correlated with the postoperative refraction. In all eyes,
      preoperative epithelial thickness was between 34 and 44 microm. In contrast,
      after surgery, values were between 35 and 111 microm. In eyes with a refractive
      outcome of +/-1.0 diopter of that intended, there was an increase of the
      epithelial thickness of less than 5 microm postoperatively. In contrast, eyes
      with severe regression showed a significant increase in the thickness in the
      epithelium after LASIK. In our patient group, regression of the attempted
      correction was related to postoperative epithelial hyperplasia. Broadly speaking,
      an increase of 10 microm epithelial thickness resulted in a 1 diopter regression.
      Mechanical and/or pharmaceutical factors controlling postoperative epithelial
      hyperplasia would be beneficial.

PMID- 9758653
TI  - LASIK for hyperopia and hyperopic astigmatism--results of a pilot study.
AB  - Laser-assisted in situ keratomileusis (LASIK) was evaluated in hyperopia and
      hyperopic astigmatism. LASIK was safe and effective in spherical hyperopia up to
      +5 D and acceptable in toric hyperopia up to +5 D but results were poor in
      hyperopia of more than +5 D.

PMID- 9758654
TI  - Hg2+ removal by genetically engineered Escherichia coli in a hollow fiber
      bioreactor.
AB  - Escherichia coli cells engineered to express an Hg2+ transport system and
      metallothionein accumulated Hg2+ effectively over a concentration range of 0.2-4
      mg/L in batch systems. Bioaccumulation was selective against other metal ions and
      resistant to changes in ambient conditions such as pH, ionic strength, and the
      presence of common metal chelators or complexing agents (Chen, S.-L.; Wilson, D.
      B. Appl. Environ. Microbiol. 1997, 63, 2442-2445; Biodegradation 1997, 8, 97
      103). Here we report the characterization of the bioaccumulation system based on
      its kinetics and an isotherm. Bioaccumulation was rapid and followed Michaelis
      Menten kinetics. A hollow fiber bioreactor was constructed to retain the
      genetically engineered cells. The bioreactor was capable of removing and
      recovering Hg2+ effectively at low concentrations, reducing a 2 mg/L solution to
      about 5 microgram/L. A mathematical equation that quantitatively described Hg2+
      removal by the bioreactor provides a basis for the optimization and extrapolation
      of the bioreactor. The genetically engineered E. colicells and the bioreactor
      system have excellent properties for bioremediation of Hg2+-contaminated
      environments.

PMID- 9758655
TI  - Modeling and analysis of co-immobilized aerobic/anaerobic mixed cultures.
AB  - Systems of co-immobilized microorganisms are highly effective for conducting two
      or more consecutive bioprocesses within close proximity of the source and the
      sink of substrates. In this work, a general model of a co-immobilized
      aerobic/anaerobic bacterial system was developed and analyzed. The model was used
      to optimize pellet design and to study the effect of slow cell growth on process
      efficiency. The analysis demonstrated that co-immobilization of bacterial species
      accelerates the rate of biotransformation and provides complete transformation of
      toxic intermediates.

PMID- 9758656
TI  - Novel membrane bioreactor with gas/liquid two-phase flow for high-performance
      degradation of phenol.
AB  - The use of a membrane bioreactor with cell retention to achieve high biomass
      concentrations has been examined for phenol degradation by the bacteria
      Alcaligenes eutrophus. This process is particularly interesting for toxic
      substrates as the hydraulic dilution rate and the growth rate are independently
      controlled. In the case of a transitory excess of phenol, this potentially toxic
      situation can be overcome by modifying the substrate concentration or the
      dilution rate without any loss of cells. The injection of a gas phase at the
      filter inlet increased both the permeate flow rate (by a factor of 1. 75) and the
      oxygen transfer capacity (by a factor of 1.5). This has enabled the cell
      concentration to reach a maximal value of 60 g L-1 with a hydraulic dilution rate
      of 0.5 h-1 and a phenol feed concentration of 8 g L-1. The volumetric
      productivity of this process corresponds to a phenol degradation rate approaching
      100 kg m-3 day-1. The on-line measurement of the characteristic yellow color of 2
      hydroxymuconate semialdehyde, a metabolic intermediate of the phenol degradation
      pathway, in the permeate provides an interesting basis for process control of
      phenol supply into the reactor since the color intensity correlates directly to
      the specific rate of phenol degradation.

PMID- 9758657
TI  - Transport in a grooved perfusion flat-bed bioreactor for cell therapy
      applications.
AB  - This study considers the transport of oxygen (a growth-associated solute) and
      lactate (a metabolic byproduct) in a flat-bed perfusion chamber modified to
      retain cells through the addition of grooves, perpendicular to the direction of
      flow, at the chamber bottom. The chamber has been successfully applied to
      hematopoietic cell culture and may be useful for other basic and applied
      biomedical applications. The objective of this study is to characterize the
      culture environment in terms of solute transport under various operational
      conditions. This will allow one to improve the design and operating strategy of
      the perfusion system for maximizing cell numbers. The system is numerically
      simulated using the finite element package FIDAP. The reaction kinetics
      describing oxygen uptake by cells are simplified to zero order to give an upper
      bound for the oxygen consumption. A flat-bed chamber without grooves is
      considered here as a benchmark. We show that the growth environment is not oxygen
      limited (local oxygen concentration above 10 microM) for a variety of flow rates
      and culture conditions (qO2 = 0.1 micromol/(10(6) cells h)). With a medium flow
      rate of 2.5 mL/min through the reactor, the model predicts that the 29-cm2
      reactor can support at least 33.4 x 10(6) total cells when the inlet medium is in
      equilibrium with high (20%) oxygen concentration. The culture becomes oxygen
      limited however for the same flow rate for low (5%) oxygen concentration and can
      only support 7.2 x 10(6) total cells. Comparison of grooved vs nongrooved
      chambers reveals that the presence of grooves only affects solute transport on a
      local scale. This result is attributed to the small size (200 microgram) of the
      cavities relative to the chamber dimensions. The comparison also yields an
      empirical relation that allows for rapid estimation of oxygen and lactate
      concentrations in the grooves using only the numerical simulation of the simpler
      nongrooved chamber. Finally, our investigation shows that, while decreasing the
      spacing between cavities decreases the total number of cells the reactor can
      support, the efficiency of the reactor is increased by 25% (on an area basis)
      without growth restriction.

PMID- 9758658
TI  - Efficient production of L-(+)-lactic acid using mycelial cotton-like flocs of
      Rhizopus oryzae in an air-lift bioreactor.
AB  - L-(+)-Lactic acid production was enhanced in a culture of Rhizopus oryzae by
      induction of a mycelial flocs morphology. By conventional culture the morphology
      of R. oryzae is that of a pellet-like cake; however, when mineral support and
      poly(ethylene oxide) are added to the culture, the morphology of R. oryzae takes
      on a cotton-like appearance. The formation of these cotton-like mycelial flocs
      was induced by the addition of 5 ppm poly(ethylene oxide) into a 12-14 h culture
      containing 3 g/L of the mineral support before the formation of the conventional
      pellet morphology. The cotton-like flocs were also formed in cultures grown in an
      air-lift bioreactor. This morphology allowed effective mass transfer inside the
      flocs and effective fluidity of culture broth in an air-lift bioreactor. L-(+)
      Lactic acid concentration produced by mycelial flocs in an air-lift bioreactor,
      with the support and poly(ethylene oxide), was 104.6 g/L with a yield of 0.87
      using 120 g/L of glucose as the substrate; for this culture without both, the
      concentration was 43.2 g/L. These results demonstrate that cotton-like mycelial
      flocs are the optimal morphology for use in the air-lift bioreactor culture of R.
      oryzae.

PMID- 9758659
TI  - Higher productivity of growth-arrested Chinese hamster ovary cells expressing the
      cyclin-dependent kinase inhibitor p27.
AB  - We constructed stable Chinese hamster ovary (CHO) cell lines which conditionally
      and coordinately express the model product gene secreted alkaline phosphatase
      (SEAP) and one of the cytostatic genes p21, p27, and p53175P, a p53 mutant
      deficient in apoptotic but not cell-cycle arrest function. The use of dicistronic
      expression technology allowed the conditional expression of the model product
      gene and the cytostatic gene in a coordinated fashion from a single expression
      unit under the control of the tetracycline-responsive promoter PhCMV-1. Due to
      the presence of a cytostatic gene in the multicistronic expression unit, the
      growth behavior of the engineered CHO cell lines could be controlled by the
      addition or withdrawal of the exogenous agent tetracycline to or from the cell
      culture medium. Withdrawal of tetracycline resulted in sustained growth arrest of
      the stable cell lines for a prolonged period. The growth arrest of such cell
      lines was found to be accompanied by a 10-15-fold increase in their production of
      SEAP per cell. This controlled proliferation technology allows the design of a
      novel two-stage production process which consists of a proliferation phase
      leading to the desired cell density, followed by an extended production phase
      during which the cells remain growth-arrested and increase cell-specific
      production of a heterologous protein.

PMID- 9758660
TI  - Scale-up and optimization of the low-temperature inducible cspA promoter system.
AB  - The performance of the major Escherichia coli cold-shock promoter in directing
      the synthesis of recombinant proteins at low temperatures was investigated in
      batch fermentations using a plasmid-encoded transcriptional gene fusion between
      the cspA promoter region and the lacZ gene. Rapid synthesis of beta-galactosidase
      was observed when the fermentation broth was chilled to 15 degreesC using a
      variety of cooling profiles, including one modeling the heat-transfer
      characteristics of a 60-L pilot plant unit. A linear cooling rate of 0.5
      degreesC/min led to optimum recovery yields. For all single-temperature downshift
      experiments, however, the promoter became repressed 60-120 min after initiation
      of cooling. Both temperature cycling between 15 and 25 degreesC and stepwise
      temperature downshifts between 37, 29, 21, and 13 degreesC led to multiple
      inductions of the cspA promoter. Nevertheless, high-efficiency reinduction was
      only observed during the first temperature pulse when the former strategy was
      used and when the cells were held at intermediate temperatures for less than 60
      min or more than 120 min in the case of successive downshifts. Promoter
      repression was abolished in host cells bearing a null mutation in the gene
      encoding the ribosomal binding factor RbfA, leading to the constitutive and high
      level expression of beta-galactosidase for 7 h postshift when shake flask
      cultures were transferred from 42 to 23 degreesC. The suitability of rbfA cells
      for cspA-driven recombinant protein production was confirmed in high-density fed
      batch fermentations. Our results are consistent with the existence of a cold
      shock-induced repressor molecule that must accumulate at a threshold
      concentration before interfering with the production of proteins placed under
      cspA transcriptional control.

PMID- 9758661
TI  - Solubilization of recombinant ovine growth hormone with retention of native-like
      secondary structure and its refolding from the inclusion bodies of Escherichia
      coli.
AB  - Ovine growth hormone was expressed in Escherichia coli in the form of inclusion
      bodies using the pQE-30 expression vector. In a simple fed-batch fermentation,
      800 mg/L of recombinant ovine growth hormone (r-oGH) was produced at a cell
      concentration of 12 g dry cell weight/L. Inclusion bodies were isolated from
      cells with >95% purity by extensive washing using detergent, and the r-oGH from
      the purified inclusion bodies was solubilized in 2 M Tris-HCl buffer at pH 12
      containing 2 M urea. The r-oGH solubilized in the above conditions exhibited
      considerable secondary structure as determined by circular dichroism spectra and
      was immunologically active. Solubilization of the inclusion body protein with
      retention of native-like secondary structure gave higher yields during refolding.
      To suppress protein aggregation, refolding was carried out in gel filtration
      column. Refolding, buffer exchange, and the purification of monomeric r-oGH from
      aggregated complex was achieved in a single step using gel filtration
      chromatography. More than 60% of the initial inclusion body protein was refolded
      into a native-like conformation by the use of this procedure. The refolded
      protein was characterized by circular dichroism, fluorescence, SDS-PAGE, Western
      blotting, and radio receptor binding assay and found to be similar to native,
      pituitary-derived, ovine growth hormone.

PMID- 9758664
TI  - Displacement chromatography using the UNO continuous bed column as a stationary
      phase 
AB  - Displacement separations of biopolymers are even more restricted in regard to the
      upper applicable limit of the flow rate than elution chromatographic ones, when
      conventional columns packed with porous particles are used. Bio-Rad has recently
      introduced a new column type, the UNO column, which contrary to conventional HPLC
      columns is not packed with particles but consists of a continuous porous polymer
      rod. The plate height of this continuous bed column was found to be nearly
      independent of the flow rate within the investigated range (0.01-4.5 mL/min, 1.56
      701.6 cm/h). The strong ion exchanger columns UNO Q1 (7 x 35 mm, 1.3 mL) and UNO
      Q6 (12 x 53 mm, 6 mL) were investigated as stationary phases for protein
      displacement chromatography at elevated flow rates. With the UNO column,
      displacement separations of alpha-lactalbumin and beta-lactoglobulin (displacer:
      poly(acrylic acid), Mw 5100) were still possible at flow rates that were 1 order
      of magnitude higher than those applicable to conventional columns of similar
      dimensions. In fact the flow rate was limited by the necessity to collect the
      protein-containing fraction fast enough for an adequate monitoring of the
      separation rather than by a loss in resolution. While the UNO Q1 column did not
      allow for the full development of the displacement train, 50 mg of protein could
      be separated using the UNO Q 6 column. Recoveries were well over 95% in this
      case. More than 50% of the alpha-lactalbumin was collected in pure and
      concentrated form (concentration by a factor of 2). The steric mass action model
      was used to optimize the displacer concentration.

PMID- 9758663
TI  - Selective adsorption/recovery of Pb, Cu, and Cd with multiple fixed beds
      containing immobilized bacterial biomass.
AB  - Fixed-bed columns packed with calcium alginate (CA)-immobilized biomass of
      Pseudomonas aeruginosa PU21 were utilized to remove lead (Pb), copper (Cu), and
      cadmium (Cd) from the contaminated water. In the absence of competing metals,
      saturation capacity of CA-immobilized cells in batch operations was 1.60, 2.42,
      and 1.06 mmol/g, for Pb, Cu, and Cd, respectively. The Langmuir constants (K)
      obtained from the Langmuir isotherm were 157.6, 4.2, and 3.7 mM-1 for Pb, Cu, and
      Cd, respectively. Results from single-metal biosorption with 10-cm immobilized
      cell columns show that, for an influent metal concentration of 193 microM, the
      total capacities for Pb, Cu, and Cd, respectively, were 5.12, 4.03, and 3.48
      mmol, which is nearly 25-30% higher than those obtained from columns containing
      only cell-free CA matrix. With the influent containing ternary mixtures of Pb,
      Cu, and Cd, columns with immobilized cells exhibited predominant selectivity to
      Pb, whereas in the cell-free columns, the dominance of Pb adsorption reduced,
      along with an appreciable increase in the adsorption of Cu. The metal-laden
      columns were regenerated by elution with HCl solution (pH 2.0). The metal
      recovery ratios were 80:1, 60:1, and 27:1 for Cu, Cd, and Pb, respectively.
      Moreover, with a pH gradient elution, the column-trapped metals can be optimally
      recovered at distinct pH values. Continuous biosorption of Pb, Cu, and Cu with
      four columns in series was also conducted. Results from the multibed operation
      demonstrate that Pb ions strongly inhibited the adsorption of Cu and Cd, which
      only occurred initially, and subsequently, an essential portion of the adsorbed
      Cu and Cd ions was replaced by Pb ions due to the ion exchange effect. However,
      since Pb ions were rapidly removed from the bulk at the onset of metal loading,
      Pb adsorption in columns 2-4 was negligible for the first 10-30 h, leading to an
      elevation in the breakthrough time (tb) and the capacity for Cu and Cd in columns
      2-4. A back-propagation neural network model was shown to be able to predict the
      breakthrough curves of the three metals in the multicolumn processes with a
      ternary-metal feed.

PMID- 9758662
TI  - Extraction and activity of chymotrypsin using AOT-DOLPA mixed reversed micellar
      systems.
AB  - Novel reversed micellar solutions formulated with a mixture of AOT (dioctyl
      sulfosuccinate) and DOLPA (dioleyl phosphoric acid) show good potential for use
      in reversed micellar protein extraction operations. Chymotrypsin is easily
      extracted from an aqueous phase into organic isooctane containing 10 mM AOT and
      DOLPA in a 4:1 ratio. The extraction ability of the mixed reversed micelles of 10
      mM was higher than that of 200 mM AOT alone. The results of extraction indicated
      that the AOT-DOLPA mixed reversed micelles are very useful for separating and
      enriching chymotrypsin. Back-extraction of chymotrypsin from the organic phase to
      a fresh aqueous phase is also accomplished by adding an alcohol to the organic
      phase. Although the back-transfer of chymotrypsin from the reversed micelles
      formed by AOT alone is very slow and difficult, in the AOT-DOLPA mixed reversed
      micelles, the back-extraction can be achieved completely by addition of 10% (v/v)
      isobutyl alcohol to the reversed micellar phase. The time to attain to the
      equilibrium of back-extraction was reduced from more than 24 to 2 h by adding the
      alcohol. On the basis of the activity data, the best composition of AOT and DOLPA
      was a 4:1 ratio and the total surfactant concentration was 10 mM. The activity of
      chymotrypsin recovered from the mixed reversed micelles was higher than that of
      the initial protein before the forward-transfer. This result means that the novel
      mixed reversed micellar solutions are useful not only in separation but also in
      purification of proteins.

PMID- 9758665
TI  - Effect of hydrodynamic and magnetic stabilization on fluidized-Bed adsorption 
AB  - Direct fermentation broth processing using fluidized beds is extremely
      advantageous due to the low operating pressure drop of the device and the ability
      of the bed to process suspended-solids-containing solutions. Unfortunately, the
      solid particles in fluidized beds typically show a great deal of mixing compared
      to those in packed beds. This mixing may lead to early breakthrough and
      inefficient use of adsorptive capacity. Stabilization reduces the solids mixing
      and improves the performance and efficiency of a fluidized bed. A comparison of
      packed, fluidized, and stabilized beds reveals that, while normal fluidized beds
      do contain a significant amount of mixing, the breakthrough behavior of the bed
      is not drastically different than that of a packed bed. Magnetic stabilization of
      the bed usually leads to an increase in adsorption efficiency but is dependent on
      field strength and orientation. Permanently magnetized beds were also
      investigated and produced breakthrough efficiencies similar to those of packed
      beds.

PMID- 9758666
TI  - The behavior of hydrocolloid coatings on vegetative materials 
AB  - Coating vegetative materials by gelling agents is a process characterized by four
      different time scales. After wetting and penetration of the vegetative skin by
      the gum solution, adhesion of the viscous solution to the outer layer (skin) of
      the coated material is possible. The gelled film (coating) collapses during
      further drying and adheres to the vegetative tissue. Critical surface tensions of
      the solid object to be coated, its apparent and real roughness, wettability of
      the surfaces by the gum solution, the composition and polarity of the films
      designed to coat the solid, and the surface tension of gum coating solutions are
      among the critical properties that need to be explored and changed for a
      successful coating process. The critical surface tensions of garlic peel and
      gellan and alginate films (coatings) were evaluated by Zisman plots. Garlic skin
      has a low surface tension compared with those of synthetic films such as
      polystyrene and polyethylene. A spreading technique was used to determine the
      surface tension of the dry film and the solid garlic skin. Surface tension was
      divided into dispersive and polar components. The similarity between the coating
      solution and the object to be coated in values of dispersive and polar components
      influences the spreadability of the coating gum solutions. Better compatibility
      between the coated object and the coating films can be achieved by incorporating
      surface-active agents within the coating gum solution. From the compatibility
      requirements detailed above, it can be concluded that tailor-made hydrocolloid
      coatings for different vegetative materials can only be achieved by further
      exploring the chemical and physical properties of the coating solutions and the
      coated objects.

PMID- 9758667
TI  - Microscopy of DNA in dilute polymer solutions.
AB  - The mechanism of separation of DNA in polymer solutions is not well understood.
      In this paper we use epifluorescence videomicroscopy to investigate the dynamic
      behavior of DNA electrophoresing through dilute polymer solutions. DNA collides
      with polymer obstacles, which cause the conformation of DNA to change from the
      globular, random coil conformation it takes in free solution. There are two main
      types of DNA-polymer collisions: U-shape collisions and brief collisions. In U
      shape collisions, the DNA collides with a polymer obstacle, extends into a U
      shape, and then slides around the polymer obstacle like a pulley. There are
      occasionally multiple entanglement points, causing the DNA to take more complex
      conformations, such as W-shapes. In the brief collision process, the DNA collides
      with a polymer obstacle and begins to extend but then collapses back into its
      globular conformation before a full U-shape is formed. The frequency of these
      interactions increases as the DNA size increases, and it also increases when the
      polymer size or concentration increases. These data support the transient
      entanglement coupling mechanism of separation of DNA, which states that
      entanglements between DNA and polymer molecules result in the separation of DNA.

PMID- 9758668
TI  - Pressure-induced dissociation of antigen-antibody complexes.
AB  - Pressures on the order of 1000-4000 bar have been reported to reversibly
      dissociate a number of oligomeric protein complexes without gross changes in
      protein structure. Here, we report that hydrostatic pressure can also dissociate
      some antigen-antibody complexes in solution. The association of fluorescent
      labeled antigens with monoclonal antibodies was monitored via increases in the
      fluorescence anisotropy upon binding. Previously, we had found that pressures of
      2000 atm were able to dissociate bovine serum albumin (BSA) from immunoadsorbents
      formed from certain antibodies but not others. In this study, we have found that
      the sensitivity to pressure in solution is present for the interaction of BSA
      with MAb 9.1 and absent for the interaction of BSA with MAb 6.1; this behavior is
      consistent with the immunoadsorbent study. The interaction of hen egg white
      lysozyme with two monoclonal antibodies was also measured. Interestingly, the
      complex with the greater electrostatic character (HyHEL-5) did not exhibit
      pressure sensitivity, as would be expected due to electrostriction effects,
      whereas the more hydrophobic complex (HyHEL-10) exhibited a strong pressure
      sensitivity. In each of the systems displaying pressure sensitivity, the free
      energy of association was found to increase linearly with pressure, indicating a
      constant change in volume between the free and bound states. Overall, these
      results indicate that some antigen-antibody complexes exhibit significant
      sensitivity to pressure, whereas others do not; the mechanisms that discriminate
      between these cases remain unresolved. Understanding and manipulation of this
      phenomenon may prove useful in a variety of processes involving the recovery from
      antigens of antibodies.

PMID- 9758669
TI  - Single- and dual-fractal analysis of hybridization binding kinetics: biosensor
      applications.
AB  - The diffusion-limited hybridization kinetics of analyte in solution to a receptor
      immobilized on a biosensor or immunosensor surface is analyzed within a fractal
      framework. The data may be analyzed by a single- or a dual-fractal analysis. This
      was indicated by the regression analysis provided by Sigmaplot. It is of interest
      to note that the binding rate coefficient and the fractal dimension both exhibit
      changes in the same direction for both the single-fractal and the dual-fractal
      analysis examples presented. For example, for a single-fractal analysis and for
      the hybridization of 10 nM 16CFl (oligonucleotide) to 16B immobilized via
      sulfosuccinimidyl-6-(biotinamido)hexanoate and streptavidin using chemical and
      thermal regeneration (Abel, A. P.; Weller, M. G.; Duveneck, G. L.; Ehrat, M.
      Widmer, H. M. Anal. Chem. 1996, 68, 2905-2912), an increase in the fractal
      dimension, Df from 1.211 (chemical regeneration) to 1.394 (thermal regeneration),
      leads to an increase in the binding rate coefficient, k, from 86.53 (chemical
      regeneration) to 100.0 (thermal regeneration). An increase in the degree of
      heterogeneity on the biosensor surface leads to an increase in the binding rate
      coefficient. When a dual-fractal analysis was utilized, an increase in the
      fractal dimension value from Df1 to Df2 leads to an increase in the binding rate
      coefficient value from k1 to k2. The fractional order of dependence of the
      binding rate coefficient, k1, on (a) the analyte (rRNA) concentration in solution
      and (b) on the fractal dimension, Df1, for the hybridization kinetics to detect
      Listeria species (Fliss, R.; St-Laurent, M.; Emond, E.; Simard, R. E.; Lemieux,
      R.; Ettriki, A.; Pandian, S. Appl. Microbiol. Biotechnol. 1995, 43, 717-724.)
      further reinforces the fractal nature of the system. The binding rate
      coefficient(s) expressions developed as a function of the analyte concentration
      in solution and the fractal dimension are of particular value since they provide
      a means to better control of biosensor or immunosensor performance.

PMID- 9758671
TI  - Intermittent light irradiation with a second-scale interval enhances caffeine
      production by coffea arabica cells 
AB  - We developed novel equipment that intermittently illuminates Coffea arabica cell
      suspensions at a second-scale interval and investigated how intermittent
      irradiation enhances caffeine biosynthesis by C. arabica cells. The light/dark
      cycles consisting of 2 s of illumination and 18 s of darkness enhanced caffeine
      production, reaching the same level as for continuous light. The intermittent
      illumination increased the production efficiency regarding light consumption by a
      factor of 10. Caffeine production was determined by light intensity regardless of
      intermittent or continuous light irradiation. We propose a new concept for
      designing a photobioreactor that is applicable to secondary metabolite production
      by plant cell culture.

PMID- 9758670
TI  - Modified electrodes with synthetic biocatalytic membranes.
AB  - A biocatalytic membrane based on an immobilized enzyme molecule has been
      prepared. Oxidative electropolymerization of 8-hydroxyquinaldine (8-OHQ) monomers
      in 0.2 M, pH 7 phosphate buffer containing glucose oxidase (GOx) has been carried
      out to modify the surfaces of GC, Au, and Pt rotating disk electrodes. The
      biocatalytic properties of the synthesized membrane were characterized by
      studying the catalytic activities of the immobilized GOx. Signals obtained from
      modified GC electrodes with this biomembrane were mainly attributed to the
      immobilized GOx. Signals obtained from modified Pt or Au electrodes were due to
      the combined contribution of the enzyme and the native electrode's material. The
      potential analytical applications of these modified electrodes as
      bioelectrochemical sensors were also investigated.

PMID- 9758672
TI  - Acetic acid production from fructose by clostridium formicoaceticum immobilized
      in a fibrous-Bed bioreactor 
AB  - The fermentation kinetics of acetic acid production from fructose by Clostridium
      formicoaceticum was studied at pH 7.6 and 37 degreesC. Recycle batch, fed-batch,
      and continuous fermentations using immobilized cells in a fibrous-bed bioreactor
      were studied for their potential application in producing acetic acid from
      fructose, a fermentable sugar commonly found in corn steep liquor and many other
      food processing wastes. For the immobilized cell fermentation, acetic acid yield
      from fructose was approximately 1.0 g/g, with a final acetate concentration of
      approximately 78 g/L and the overall reactor productivity (based on the fibrous
      bed bioreactor volume) of approximately 0.95 g/(L.h) in the fed-batch
      fermentation. For a similar fed-batch fermentation with free cells, acetic acid
      yield was approximately 0.9 g/g, the highest final acetate concentration was
      approximately 46 g/L, and the overall productivity was approximately 0.12
      g/(L.h). In the continuous fermentation with immobilized cells, the reactor
      productivity decreased from 3.2 to 1. 3 g/(L.h) as retention time increased from
      16 to 72 h to reach 100% conversion. Compared to free-cell fermentations, the
      superior performance of the fibrous-bed bioreactor can be attributed to the high
      density (>30 g/L) of viable cells immobilized in the fibrous bed. The
      fermentation product, acetic acid, was found to be a noncompetitive inhibitor to
      the cells. However, the immobilized cells had a higher maximum production rate
      (pmax) and a higher value for the inhibition rate constant (Kp) than those for
      the free cells, suggesting that the immobilized cells in the fibrous-bed
      bioreactor were less sensitive to acetic acid inhibition than the free cells.
      This improvement in kinetic behaviors for immobilized cells confirms that the
      fibrous-bed bioreactor can be used as an effective tool for adapting and
      screening for acetate-tolerant strains.

PMID- 9758673
TI  - Application of logistic growth model to pharmacodynamic analysis of in vitro
      bactericidal kinetics.
AB  - A new pharmacodynamic model for the analysis of in vitro bactericidal kinetics
      was developed based on the logistic growth model, with the bacterial phases
      divided into two compartments. The model equations are expressed as nonlinear
      simultaneous differential equations, and the Runge-Kutta-Gill method was adopted
      to numerically solve the equations in both the simulation and the least squares
      curve-fitting procedures. The model can describe the initial killing and the
      regrowth phases and can explain the nonlinear dependence of the killing rate on
      the drug concentration. The model can also explain the plateau in the bacterial
      growth curve that is often observed in in vitro experiments. The model was
      applied to analysis of the in vitro time-killing data of beta-lactam antibiotics,
      S-4661, meropenem, imipenem, cefpirome, and ceftazidim against three types of
      bacteria, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus.
      The results of curve-fitting using the least squares program MULTI (Runge) showed
      good fits for all types of drugs and bacteria. The relationship between the
      characteristics of the drug-bacteria interactions and the estimated
      pharmacodynamic parameters is discussed.

PMID- 9758674
TI  - Inhibition of desipramine hydroxylation (Cytochrome P450-2D6) in vitro by
      quinidine and by viral protease inhibitors: relation to drug interactions in
      vivo.
AB  - Pharmacokinetic drug interactions with viral protease inhibitors are of potential
      clinical importance. An in vitro model was applied to the quantitative
      identification of possible interactions of protease inhibitors with substrates of
      cytochrome P450-2D6. Biotransformation of desipramine (DMI) to hydroxydesipramine
      (OH-DMI), an index reaction used to profile activity of human cytochrome P450
      2D6, was studied in vitro using human liver microsomes. Quinidine and four viral
      protease inhibitors currently used to treat human immunodeficiency virus
      infection were tested as chemical inhibitors in this system. Formation of OH-DMI
      from DMI was consistent with Michaelis-Menten kinetics, having a mean Km value of
      11.7 microM (range: 9.9-15.3 microM). Quinidine, a highly potent and relatively
      selective inhibitor of P450-2D6, strongly inhibited OH-DMI formation with an
      apparent competitive mechanism, having a mean inhibition constant of 0.16 microM
      (range: 0.13-0.18 microM). All four protease inhibitors impaired OH-DMI
      formation; the pattern was consistent with a mixed competitive-noncompetitive
      mechanism. Mean inhibition constants (small numbers indicating greater inhibiting
      potency) were as follows: ritonavir, 4.8 microM; indinavir, 15.6 microM;
      saquinavir, 24.0 microM; nelfinavir, 51.9 microM. In a clinical pharmacokinetic
      study, coadministration of ritonavir with DMI inhibited DMI clearance by an
      average of 59%. The in vitro findings, together with observed plasma ritonavir
      concentrations, provided a reasonable quantitative forecast of this interaction,
      whereas estimated unbound plasma or intrahepatic ritonavir concentrations yielded
      poor quantitative forecasts. Thus the in vitro model correctly identifies
      ritonavir as a potent and clinically important inhibitor of human P450-2D6. Other
      protease inhibitors may also inhibit 2D6 activity in humans, but with lower
      potency than ritonavir.

PMID- 9758675
TI  - Evaluation of pluronic F127-based sustained-release ocular delivery systems for
      pilocarpine using the albino rabbit eye model.
AB  - The overall objective of this study was to develop Pluronic F127 (PF127)
      containing formulations of pilocarpine hydrochloride (PHCL) which can be used for
      sustained-release ocular delivery of PHCL. The PF127 formulations of PHCL
      containing methylcellulose (MC) or hydroxypropyl methylcellulose (HPMC) as an
      additive had previously exhibited the slowest dissolution rates and released the
      drug the slowest in vitro. This study was performed to assess the in vivo
      performance of these two formulations using miosis in the albino rabbit eye
      produced by PHCL as a measure of ocular bioavailability. The PF127MC formulation
      (20 microL) had a significantly greater intensity of miosis compared to the same
      volume of an isotonic solution of PHCL. The duration and the intensity of the
      miotic response increased significantly as the instilled volume of the PF127MC
      gel formulation increased. The miotic response, expressed as % bioactivity by
      assigning a value of 100% to the 20 microL PF127MC treatment, was increased as
      the volume instilled was reduced from 60 to 20 microL. However, no difference in
      bioactivity between the 60 and 100 microL volumes was observed. In addition, the
      100 microL volumes of both the PF127MC and PF127HPMC gel formulations exhibited
      bioactivity equivalent to 20 microL of an isotonic PHCL solution. Thus, for a
      given instilled concentration, the larger the volume instilled the greater the
      amount of drug present in tear fluid and thus the higher the concentration
      delivered to the iris sphincter muscle and hence the greater the miotic response.
      However, the fraction of the dose reaching the iris sphincter muscle was greater
      for the smaller instilled volume. On the basis of these findings and previous in
      vitro results, the PF127 formulations of PHCL having MC or HPMC as an additive
      showed considerable potential as sustained-release ocular delivery systems for
      PHCL. This conclusion was based upon their ability to provide a substantial
      prolongation of drug action and an improvement in the ocular bioavailability of
      pilocarpine compared to conventional eye drops and previously utilized PF127
      formulations of PHCL. It appears that ocular bioavailability can be increased
      more readily by altering both the rheological characteristics of the delivery
      system and by using a smaller dose volume.

PMID- 9758676
TI  - Enhanced colonic and rectal absorption of insulin using a multiple emulsion
      containing eicosapentaenoic acid and docosahexaenoic acid.
AB  - The aim of this study was to test the effects of eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) on insulin absorption from rat intestinal loops in
      situ, using a water-in-oil-in-water (W/O/W) multiple emulsion. The enhancement
      effect of these long-chain polyunsaturated fatty acids was compared with that of
      free fatty acids having a C18 alkyl chain. The emulsion (insulin dose, 50
      units/kg) was administered directly into the colonic and rectal loops. Both EPA
      and DHA strongly enhanced insulin absorption and induced hypoglycemia after
      colonic and rectal dosing. Comparing the pharmacological availability, the order
      of effectiveness with respect to the enhanced absorption of insulin was DHA >/=
      EPA > C18 unsaturated fatty acids >> C18 saturated fatty acid at both sites. DHA
      showed greater effects upon rectal dosing than upon colonic dosing. Histological
      studies revealed that the emulsion incorporating DHA did not induce gross
      morphological changes in the structure of the intestinal mucosa. Our results
      indicate that a W/O/W multiple emulsion incorporating DHA is a possible means of
      facilitating the intestinal absorption of insulin without inducing any serious
      damage to the epithelial cells.

PMID- 9758677
TI  - Palmitoyl derivatives of interferon alpha: potential for cutaneous delivery.
AB  - Palmitoyl derivatives of interferon alpha2b (p-IFNalpha) were prepared by
      covalent attachment of the fatty acid to lysine residues in the protein through a
      reaction with N-hydroxysuccinimide palmitate ester. The p-IFNalpha was
      characterized by capillary electrophoresis (CE), mass spectrometry (MS), SDS
      PAGE, and antiviral assay. Flow-through diffusion cells and human breast skins
      were used to measure cutaneous and percutaneous absorption. Formation of p
      IFNalpha derivatives was demonstrated by CE to be dependent on reaction time and
      reagent: protein ratio. Electrospray MS of the crude p-IFNalpha mixture indicated
      three populations of IFNalpha derivatives with 10, 11, and 12 palmitoyl
      substitutions. The addition of palmitoyl residues to IFNalpha under the
      conditions described reduced the antiviral specific activity by 50%. However, the
      cutaneous absorption of p-IFNalpha was about 5-6 times greater than the parent
      protein. The amount of p-IFNalpha and IFN alpha in whole skin after 24 h of
      treatment was 2.106 +/- 1.216 microg/cm2 and 0.407 +/- 0.108 microg/cm2,
      respectively. Approximately two times higher flux was detected for p-IFNalpha
      compared to the nonfatty acylated IFNalpha. The total amount of drug diffused in
      24 h was also approximately two times higher for the p-IFNalpha. The results
      indicate a potential for using fatty acylated derivatives of IFN alpha for dermal
      and transdermal delivery.

PMID- 9758678
TI  - Site-specific drug delivery in the dog using flexible fiberoptic endoscopy.
AB  - The development of a nonsurgical repeatable method of site-specific delivery to
      the gastrointestinal tract in the canine is described. Studies to characterize
      and validate this method were performed utilizing propranolol and etodolac due to
      their well-known pharmacokinetic properties. Using a catheter placed through the
      auxiliary port of a flexible fiberoptic endoscope, liquid dosage formulations
      were consistently delivered to the canine stomach, duodenum, ileum, and colon. It
      was shown that differences in site-specific delivery could be demonstrated with
      this model. Propranolol tended to have the highest exposure following dosing to
      the ileum as compared to other sites. The anesthetic regimen used to perform
      endoscopy affected certain pharmacokinetic parameters of the compounds being
      tested including decreasing the intrinsic clearance of propranolol. However,
      since decreased intrinsic clearance should similarly affect AUCo regardless of
      the site of delivery, this does not preclude site-specific comparisons to be
      made. Further, no evidence has been reported for the effect of anesthesia on one
      GI segment but not another. Thus for other compounds, assuming there are either
      no anesthetic effects on intestinal pharmacokinetic parameters (absorption,
      intestinal metabolism, etc.) or that they are consistent and uniform throughout
      the intestinal tract, this model allows comparisons of the exposure following
      delivery to differing intestinal sites.

PMID- 9758680
TI  - Enhanced transdermal delivery of sex hormones in swine with a novel topical
      aerosol.
AB  - This study investigated the enhanced transdermal delivery of testosterone (Tes)
      and estradiol (E2) in swine in vivo with novel metered-dose topical aerosols
      containing the penetration enhancer padimate O (PadO) and predicted the dose
      deliverable in humans from the calculated drug flux across the skin. Weanling
      swine were catheterized and castrated under general anaesthesia and used as a
      conscious hypogonadal model. Tes and E2 (with and without PadO) were applied
      once, and venous blood samples were taken over 24 h. Tes and E2 plasma levels
      were determined by radioimmunoassay. After daily topical dosing of Tes for 6
      days, the plasma Tes levels were determined and the transdermal flux was
      calculated by correcting the pseudo steady-state plasma concentration versus time
      profile with the clearance of an iv dose within the same swine. After a single
      application of the E2 aerosol over 30 cm2, or the Tes aerosol over 180 cm2, the
      mean AUC0-24 h when PadO was included in the spray was 14.1- and 2.0-fold greater
      than control, respectively (p < 0.03). After the sixth application of the Tes
      spray with PadO, the mean flux (+/-SE, n = 4) across swine skin in vivo was 2.12
      +/- 0.35 microg/cm2.h, which gave a predicted flux in humans of 0.95
      microg/cm2.h. From these data the expected plasma levels of Tes in hypogonadal
      men would compare well with the normal diurnal Tes profile in healthy men. These
      novel topical aerosols are capable of enhanced transdermal delivery of sex
      hormones in vivo, and they have the potential to deliver clinically relevant
      doses to humans.

PMID- 9758679
TI  - Enhanced skin permeation of sex hormones with novel topical spray vehicles.
AB  - The feasibility of using some novel topical spray vehicles for enhanced
      transdermal delivery of the sex hormones, testosterone (Tes), estradiol (E2),
      progesterone (Prog), and norethindrone acetate (NA) has been investigated. The
      new penetration enhancers, padimate O (PadO) and octyl salicylate (OSal) were
      used and compared with laurocapram (AZ) and oleic acid (OA). A finite dose (5
      microL/cm2) of each vehicle was applied to either shed snake skin or swine skin
      in vitro, and the amount penetrated was measured with flow-through diffusion
      cells. Partitioning into swine skin was determined after an exposure time of 1
      min. Rapid partitioning of Tes and PadO into swine skin occurred after 1 min with
      70% and 60% of the applied dose, respectively, remaining in the skin after the
      unabsorbed dose was removed by rinsing with absolute ethanol. The cumulative
      amount at 24 h (Q24 h) of Tes penetrating across the snake skin was significantly
      enhanced (p < 0.05) up to 6-fold for OSal, 3-fold for OA and AZ, and 2-fold for
      PadO compared to control. Using PadO or AZ, the Q24 h ranged from three- to
      thirteen-fold over control (p < 0.05) for E2, Prog, and NA. Extrapolation of
      these data to predict what would happen in humans suggests that it should be
      possible to deliver clinically relevant amounts of sex hormones in this manner
      with once daily dosing.

PMID- 9758681
TI  - Transdermal delivery of estradiol in postmenopausal women with a novel topical
      aerosol.
AB  - The objective of this study was to determine if a novel metered-dose topical
      aerosol (MDTA) formulation containing the new dermal penetration enhancer,
      padimate O, could enhance the transdermal delivery of estradiol to an extent that
      would result in clinically relevant plasma concentrations. The estradiol MDTA
      (with padimate O) was applied once daily at 0800 h to postmenopausal women for 9
      days, and plasma estradiol and estrone was measured daily (24 h postapplication)
      by radioimmunoassay. The topical dose was administered as three 1 mg doses of
      estradiol, each applied as a single spray over 10 cm2 which were placed adjacent
      to each other on the subject's ventral forearm. None of the subjects tested
      showed any sign of skin irritation at the application site over the entire study
      period using the Draize irritation score. In four postmenopausal women (age 54-63
      years, weight 67-93 kg) the mean estradiol level 24 h postapplication over the 9
      day study period was 53 pg/mL. This result was significantly greater (p < 0.001)
      than the baseline value of 13 pg/mL. The mean estradiol/estrone ratio also rose
      significantly (p < 0.04) from a baseline value of 0.2 up to 0.8. We conclude that
      this novel MDTA formulation significantly enhances the transdermal delivery of
      estradiol to allow a clinically relevant dose of estradiol to be delivered in
      postmenopausal women with once daily dosing.

PMID- 9758683
TI  - Some relationships between the physical properties of various 3-acyloxymethyl
      prodrugs of phenytoin to structure: potential in vivo performance implications.
AB  - Physicochemical properties of neutral N-acyloxyalkyl derivatives of phenytoin in
      aqueous, organic solvents and simulated intestinal fluid were evaluated. Based on
      the hypothesis that these low melting prodrugs may have improved physical
      properties such as solubility and dissolution rate in gastrointestinal fluid, an
      enhanced bioavailability of these prodrugs may be observed relative to phenytoin.
      Melting points, aqueous solubilities, and octanol-water (Poct) and cylcohexane
      water (Pcyc) partition coefficients of phenytoin and its prodrugs were
      determined. A simulated intestinal bile salts-lecithin mixture (SIBLM) was also
      prepared to possibly mimic the intestinal fluid content. Solubility and
      dissolution rates of phenytoin and its prodrugs were conducted in aqueous buffer
      and SIBLM. Apparent micelle-water partition coefficients (Kapp) were calculated
      by using the aqueous and SIBLM equilibrium solubility data. These properties were
      qualitatively or quantitatively correlated to the alkyl chain length of the
      prodrugs. The melting points and aqueous solubilities of all the prodrugs were
      lower than that of the parent compound, phenytoin. The apparent micelle-water
      partition coefficient increased with an increase in chain length but unlike the
      octanol-water and cyclohexane-water partition coefficients the relationship was
      complex. There was a disproportionate increase in the interaction between the
      micelle and the prodrug with the prodrugs with alkyl groups larger than four
      carbons. In SIBLM, the solubilities and dissolution rates were increased to a
      greater extent for the prodrugs than that for phenytoin. The implications are
      that the bioavailability of phenytoin from these prodrugs may be comparable to or
      higher than that of phenytoin despite having lower aqueous solubilities,
      especially after a meal inducing bile flow.

PMID- 9758682
TI  - Arterial uptake of biodegradable nanoparticles: effect of surface modifications.
AB  - Restenosis is the reobstruction of an artery following interventional procedures
      such as balloon angioplasty or stenting. Local pharmacotherapeutic approaches
      using controlled release systems are under investigation to inhibit the regional
      pathophysiologic process of restenosis. We have been investigating biodegradable
      nanoparticles (100 +/- 39 nm in diameter, mean +/- sd) for the local intra
      arterial drug delivery. The purpose of this study was to investigate nanoparticle
      surface modifications (see Table 1) to enhance their arterial uptake. The PLGA
      (polylactic polyglycolic acid copolymer) nanoparticles were formulated by an oil
      in-water emulsion solvent evaporation technique using a 2-aminochromone (U-86983,
      Upjohn and Pharmacia) (U-86) as a model antiproliferative agent. The various
      formulations of nanoparticles were evaluated for the arterial wall uptake by
      using an ex-vivo dog femoral artery model. The selected formulations were then
      tested in vivo in acute dog femoral artery and pig coronary artery models. The
      nanoparticles surface modified with a cationic compound,
      didodecyldimethylammonium bromide (DMAB), demonstrated 7-10-fold greater arterial
      U-86 levels compared to the unmodified nanoparticles in different ex-vivo and in
      vivo studies. The mean U-86 levels were 10.7 +/- 1.7 microg/10 mg (dog) and 6.6
      +/- 0.6 microg/10 mg (pig) in the artery segments ( approximately 2 cm) which
      were infused with the nanoparticles. The pig coronary studies further
      demonstrated that the infusion of nanoparticles with higher U-86 loading reduced
      the arterial U-86 levels, whereas increasing the nanoparticle concentration in
      the infusion solutions increased the arterial U-86 levels. The biodistribution
      studies in pigs following coronary arterial administration of nanoparticles
      demonstrated disposition of U-86 in the myocardium and distally in the liver and
      the lung. The mechanism of enhanced arterial uptake of the DMAB surface modified
      nanoparticles seems to be due to the alteration in the nanoparticle surface
      charge. The unmodified nanoparticles had a zeta potential of -27.8 +/- 0.5 mV
      (mean +/- sem, n = 5), whereas the DMAB modified nanoparticles demonstrated a
      zeta potential of +22.1 +/- 3.2 mV (mean +/- sem, n = 5). The adsorption of DMAB
      to the nanoparticle surface followed the Freundlich isotherm with binding
      capacity k = 28.1 microg/mg and affinity constant p = 2. 33. In conclusion,
      surface modified nanoparticles have potential applications for intra-arterial
      drug delivery to localize therapeutic agents in the arterial wall to inhibit
      restenosis.

PMID- 9758684
TI  - In vitro displacement by rat serum of adsorbed radiolabeled poloxamer and
      poloxamine copolymers from model and biodegradable nanospheres.
AB  - Poloxamer 407 and poloxamine 908 have been used by many research groups to modify
      the surface of both model latex and biodegradable nanospheres, thereby producing
      nanospheres that have shown reduced protein adsorption in vitro and extended
      circulation times in vivo. A potential limitation of such systems is the
      desorption of the copolymer coating layer. We describe a two-stage process to
      radiolabel poloxamer 407 and poloxamine 908 that has facilitated an investigation
      into this potential desorption, in vitro. The first stage of the labeling
      procedure involved the substitution of the terminal hydroxyl groups in each
      poly(ethylene oxide) (PEO) chain of poloxamer 407 and poloxamine 908 with an
      amino group. The aminated copolymers were then radiolabeled with 125Iodine Bolton
      Hunter reagent. The efficiency of labeling was calculated to be approximately 20%
      for the tetramine poloxamine 908 and approximately 33% for the diamine poloxamer
      407. Remaining free amino groups were then either acetylated, using acetic
      anhydride, or left in the free amino form. Covalent linkage of the radiolabel to
      the copolymer was confirmed by nuclear magnetic resonance (NMR) and infrared (IR)
      spectroscopy. The stability of the link between radiolabel and copolymer to
      hydrolysis was also confirmed; <4% loss of radiolabel occurred from poloxamine
      908 after incubation in phosphate-buffered saline (PBS) at 37 degrees C for 8
      days. The radiolabeled copolymers (with the free amino groups acetylated) were
      then used in experiments that have given the first direct evidence that adsorbed
      copolymers can be displaced by serum proteins in significant amounts from the
      surface of model and biodegradable nanospheres. The displacement was highly
      dependent on copolymer-nanosphere compatibility, with up to 78% of 125I tetramine
      poloxamine 908 being displaced from poly(lactide-co-glycolide) (PLGA) nanospheres
      in 24 h, compared with 20% displacement of 125I tetramine poloxamine 908 in 24 h
      from polystyrene nanospheres. These results have direct implication for the
      future design of drug delivery systems based on coated nanospheres.

PMID- 9758686
TI  - A pharmacokinetic/pharmacodynamic comparison of SAAM II and PC/WinNonlin modeling
      software.
AB  - This paper presents a detailed comparison of the kinetic analysis software
      packages SAAM II and PCNonlin/WinNonlin, based on benchmark modeling problems
      reported in "Pharmacokinetic andPharmacodynamic Data Analysis: Concepts and
      Applications" (Gabrielsson and Weiner, 1994) and seven additional models. For
      each model, both software packages were presented with identical implementations.
      Models were initially executed in PCNonlin or WinNonlin and automated comparisons
      with SAAM II made using Microsoft Test. Models investigated included one- and
      multicompartment models with nonlinearities, multiple inputs and samples,
      multiple simultaneous experiments, and linear equations. Maximum number of
      compartments, data sets, and parameters were 9, 5, and 10, respectively. We
      compared 88 different models, many of them in different configurations, e.g.,
      different weighting schemes or different parameter limits. The total number of
      attempted comparisons between SAAM II and PCNonlin was 161, of which 142 executed
      without problems. Parameter estimates, their precision (standard errors), and
      model predictions were compared; a difference of 1% or less was considered
      "agreement". Observed differences, mainly in parameter standard errors, can be
      accounted for in terms of different optimization algorithms, convergence
      criteria, and individual capabilities. In general, there was good agreement (<1%
      difference) between SAAM II and PCNonlin in terms of parameter estimates and
      model predictions. However, due to differences in the optimization procedure,
      parameter standard errors showed considerable differences. Additionally, there
      were differences when multiple data sets were fitted, indicating the importance
      of different fitting procedures for interpreting multiple kinetic data sets. The
      full results of the comparison and the model files in SAAM II and
      PCNonlin/WinNonlin formats are available from the authors.

PMID- 9758685
TI  - Partitioning and localization of spin-labeled amantadine in lipid bilayers: an
      EPR study.
AB  - EPR was used to study the distribution of the spin-labeled amantadine (AA-SL)
      between the bulk hydrophobic-hydrocarbon solvent, light paraffin oil, and water
      and between hydrophobic-hydrocarbon chain region of lipid membranes and water.
      The AA-SL molecules were soluble in both hydrophobic and polar regions of
      investigated systems. It was shown that the partition coefficient of AA-SL
      between the hydrocarbon region of the L-alpha-dimyristoylphosphatidylcholine
      fluid-phase membrane and water is much higher than between bulk hydrocarbon
      solvent and water. Furthermore, the partitioning of AA-SL into membranes of
      multilamellar liposomes made of L-alpha-dimyristoylphosphatidylcholine, L-alpha
      dipalmitoylphosphatidylcholine, and L-alpha-distearoylphosphatidylcholine was
      studied as a function of temperature, indicating no abrupt change at the main
      phase transition of these membranes. It is also clear from our data that AA-SL
      can penetrate into the gel-phase membrane practically with the same partitioning
      as into the fluid-phase membrane. Furthermore, it was shown that at least part of
      the AA-SL molecule is deeply buried in the hydrocarbon chain region of the
      membrane.

PMID- 9758687
TI  - A partial area difference analysis for estimat- ing elimination rate constants
      and DistributionVolumes of metabolites 

PMID- 9758688
TI  - alpha4 and alpha5 integrins costimulate the CD3-dependent proliferation of fetal
      thymocytes.
AB  - Although integrin receptors have been shown to function as costimulatory
      molecules on mature thymocytes and T cells, it is not known whether these
      receptors can function as costimulatory molecules on immature thymocytes.
      Previous studies have shown that the expression of alpha4 and alpha5 integrins
      were significantly higher on immature, adult CD4(-)CD8(-) thymocytes than on
      either mature thymocytes or T cells, suggesting that these receptors are involved
      in early thymocyte development. In this study, we show that day 16 fetal
      thymocytes express levels of alpha4 and alpha5 equivalent to those of adult CD4(
      )CD8(-) thymocytes. Immobilized fibronectin, a ligand for alpha4 and alpha5
      integrins, was found to enhance the CD3-dependent proliferation of these fetal
      thymocytes. In the presence of IL-7, the magnitude of the proliferative response
      increased with time of incubation, resulting in a dramatic increase in the
      percentage of gammadelta thymocytes. The enhancement of proliferation by
      fibronectin was abrogated by soluble antibodies against alpha4 and alpha5,
      whereas immobilized mAb to alpha4 and alpha5 substituted for fibronectin in
      enhancing CD3-dependent proliferation, demonstrating that alpha4 and alpha5
      integrins were responsible for the enhanced proliferation by fibronectin. Anti
      alpha4 mAb enhanced proliferation of fetal thymocytes by 100%, whereas anti
      alpha5 mAb and anti-CD28 mAb enhanced proliferation by 25%. Other costimulatory
      molecules, such as CD2, FcRgamma, and Thy-1, had no effect on the CD3-dependent
      proliferation of day 16 fetal thymocytes. This study demonstrates that alpha4 and
      alpha5 integrins are capable of costimulating fetal thymocytes.

PMID- 9758689
TI  - Idiosyncratic alterations of TCR size distributions affecting both CD4 and CD8 T
      cell subsets in aging mice.
AB  - We have used a spectratyping method, which displays the size distribution for the
      complementarity-determining region 3 (CDR3) for T cells utilizing a specific TCR
      Vbeta gene, to examine the effects of aging on the TCR repertoire of (BALB/c x
      C57BL/6)F1 hybrid mice. Although the size distributions from T cells of 8-month
      old mice were typically symmetrically shaped around one or two bands of
      intermediate size, spectratypes from mice 16 or 24 months of age were frequently
      distorted, with specific size classes either over- or underrepresented compared
      to normal young controls. Each of 12 mice tested at 16 or 24 months of age had a
      skewed spectratype for at least one of the 24 Vbeta families examined, and some
      mice had more than 50% of their spectratypes skewed significantly, as judged by a
      chi2 test. Comparable age-associated skewing of the T cell repertoire occurred in
      the CD4 and CD8 subsets, and every mouse over 16 months of age exhibited at least
      one skewed Vbeta family in both the CD4 and CD8 populations. Although the mice
      were genetically identical and raised in common facilities, their spectratype
      patterns were nonetheless idiosyncratic: i.e., the specific set of abnormalities
      was distinct for each individual old mouse. Whether these distortions of the TCR
      repertoire in middle-aged and older mice lead to alterations in immune function
      remains to be determined.

PMID- 9758690
TI  - Activation of donor-specific CTL in a tolerant recipient of cardiac allograft.
AB  - Permanent graft acceptance was induced with cyclosporine A in a low responder rat
      strain combination PVG (RT1(c)) to DA (RT1(av1)) of cardiac transplants.
      Challenge (alloimmunization) with donor and third-party WF (RT1(u)) cells was
      performed and followed by the analysis of alloreactive cytotoxicity. The
      cytotoxic T lymphocytes (CTL) from recipients with permanently accepted cardiac
      grafts manifested cytolytic activity against third-party target cells but not
      against donor target cells. The findings demonstrated unresponsiveness to be
      donor-specific, i.e., transplant tolerance was present. This was verified by
      retransplantation of the DA recipient with either a second PVG heart (which was
      accepted) or a third-party (WF) heart (which was rejected). Restoration of donor
      specific CTL after injection of exogeneous interleukin(IL)-2 concomitant with
      challenge showed that the donor-specific CTL were not depleted, but unable to be
      activated as a consequence of IL-2 deficiency. Despite donor-specific CTL
      activation in vivo the recipients failed to reject their established grafts,
      implying an ongoing presence of suppression.

PMID- 9758691
TI  - Regulation of interleukin-12 production in human cells stimulated with
      Mycobacterium bovis BCG.
AB  - Interleukin 12 (IL-12) is a monokine which plays a critical role in resistance to
      Mycobacterium tuberculosis infection. However, little is known about the
      regulation of IL-12 production by human cells stimulated with BCG. Here we report
      that in vitro infection of human mononuclear cells with M. bovis BCG induces the
      release of IL-12 protein. We also observed that the ability of BCG to stimulate
      release of IL-12 from human cells was significantly inhibited by IL-10. The
      inhibitory effect of IL-10 on the secretion of IL-12 was specific, as it was
      significantly abolished in the presence of anti-IL-10 neutralizing monoclonal
      antibody. These results were further confirmed as anti-IL-10 antibodies markedly
      increased the levels of IL-12, suggesting that BCG-induced IL-10, as well as
      exogenous IL-10, can regulate IL-12 production by human cells stimulated with M.
      bovis BCG. Interestingly, IFN-gamma production in response to BCG had no
      significant increase by the addition of neutralizing antibodies to IL-10.
      Moreover, anti-IL-12 antibodies markedly reduced the levels of IFN-gamma produced
      by BCG-stimulated human cells and abrogated the capacity of anti-IL-10 to
      increase BCG-induced IFN-gamma. These studies are the first to demonstrate a
      regulatory effect on IL-12 production by human cells infected with M. bovis BCG
      and at the same time suggest that IL-12 may play an essential role during the
      human immune response to M. bovis BCG stimulation.

PMID- 9758692
TI  - Endothelial antigen presentation: stimulation of previously activated but not
      naive TCR-transgenic mouse T cells.
AB  - In vitro experiments have shown that endothelial cells can function as antigen
      presenting cells to CD4(+) T lymphocytes. The studies presented here address the
      question of whether naive versus previously activated CD4(+) helper T cells
      differ in their responses to endothelial antigen presentation. TCR-transgenic
      mice were used as a source of naive T cells of defined antigen specificity. These
      cells were stimulated in vitro with antigen and splenic antigen-presenting cells
      to generate populations of T lymphocytes with a previously activated/memory
      phenotype. Two different types of mouse endothelial cells were used as antigen
      presenting cells, including the SVEC4-10 line derived from lymph node endothelium
      and primary murine pulmonary microvascular endothelium. Monolayer cultures of
      both types of endothelium were capable of antigen-dependent stimulation of
      previously activated TCR-transgenic CD4(+) cells. In contrast, neither
      endothelial type could activate naive CD4(+) T cells. When costimulatory signals
      were provided in trans by the addition of MHC-mismatched mouse spleen cells,
      activation of naive T cells by endothelial antigen presentation could be
      demonstrated. The expression of ICAM-1 or VCAM-1 on the endothelial cells was not
      sufficient to activate naive T cells. Furthermore, the mouse lung endothelium
      constitutively expresses B7-1, and therefore, the inability of endothelium to
      stimulate naive T cells could not be attributed to a lack of CD28-ligands. These
      studies suggest that the potential role of endothelial antigen presentation in
      immune responses is restricted to promoting responses by T cells which have
      previously encountered antigen presented by other antigen-presenting cells.

PMID- 9758693
TI  - Direct cellular interaction with activated CD4(+) T cells overcomes
      hyporesponsiveness of B-cell chronic lymphocytic leukemia in vitro.
AB  - The proliferative response of clonal B cells from patients with chronic
      lymphocytic leukemia (B-CLL) is drastically reduced compared to normal B
      lymphocytes stimulated via the B cell antigen receptor complex or by CD40
      ligation. In the present study we demonstrate that hyporesponsiveness of CLL-B
      cells can be overcome by stimulatory pathways mediated by activated CD4(+) T
      cells. In contrast to CD40 ligation, costimulation with activated T cells
      promotes a proliferative response in CLL-B cells identical to that in normal B
      cells. Furthermore, coculture with activated T cells improved survival of CLL-B
      cells in vitro. Differentiation of CLL-B cells into IgM producing cells was
      promoted, as well. However, the capacity for IgM secretion remained impaired
      compared to that of normal B cells. For T-cell-mediated B cell activation direct
      cellular contact with activated T helper cells is absolutely required. Prevention
      of CD40/CD40L interaction by CD40 antibody caused only partial inhibition of B
      cell activation, suggesting that additional signals are involved in T-B cell
      interaction. Whereas interruption of the ligand pairs CD11a/CD54, CD5/CD72,
      CD27/CD70 had no influence, the addition of CD58 antibody completely inhibited B
      cell activation by activated T cells. In costimulation with cellular signals the
      presence of B-cell-tropic cytokines, such as IL-2 and IL-4, was required to
      optimize B-CLL proliferation, as demonstrated by the use of neutralizing
      antibodies. We conclude from these results that proliferative hyporesponsiveness
      by CLL-B cells can be circumvented by antigen-nonspecific signals in addition to
      CD40 which are mediated by direct contact with activated T helper cells.

PMID- 9758694
TI  - Development of phagocytic function of cultured human monocytes is regulated by
      cell surface IL-10.
AB  - Monocytes differentiating in vitro into macrophages increase their capacity to
      ingest particles via FcgammaR and CR3. Because human recombinant IL-10 is a
      potent up-regulator of phagocytosis in human monocytes, we investigated whether
      spontaneously produced IL-10 could be a signal for the modulation of phagocytosis
      by cultured monocytes. We show here that culture of monocytes in the presence of
      anti-IL-10 mAb completely abolished up-regulation of phagocytosis of both EIgG
      and EIgMC3bi, suggesting a role for spontaneously produced IL-10 in the
      modulation of phagocytosis by cultured human monocytes. The inhibition exerted by
      anti-IL-10 mAb on the development of FcgammaR-mediated ingestion was dependent on
      the concomitant inhibition of FcgammaRIII induction in cultured cells. On the
      other hand, a similar down-regulation of CR3 expression was not involved in the
      inhibitory effect exerted by anti-IL-10 mAb on the development of CR3-mediated
      ingestion. Monocytes secreted detectable levels of IL-10 when cultured in medium
      but the concentrations of IL-10 in the supernatants decreased with length of time
      in culture, the decrease being completely reversed by anti-IL-10 mAb. In
      addition, we showed that monocytes expressed immunoreactive IL-10 on their
      surface and this expression increased during differentiation into macrophages.
      Whether this IL-10 was bound to specific membrane receptors or it was an integral
      membrane protein remains to be determined; however, this latter possibility is
      consistent with our observations that IL-10 did not elute with acid treatment and
      exogenous IL-10 did not increase surface staining of monocytes. Our data indicate
      that human mononuclear phagocytes express IL-10 on their membrane and suggest
      that this cytokine may represent an autocrine signal for the increased phagocytic
      function observed during differentiation of monocytes into macrophages.

PMID- 9758695
TI  - Early phosphorylation events induced by DPIV/CD26-specific inhibitors.
AB  - Dipeptidyl peptidase IV (DPIV, CD26) is known to be involved in the regulation of
      T lymphocyte and NK cell activation and proliferation in vitro. The molecular
      events of lymphocyte activation mediated by this ectopeptidase as well as their
      physiological ligands are only partly established. Particularly, the necessity of
      catalytic dipeptidase activity for the costimulatory function of this molecule
      has been controversial. Here we provide evidence for a direct involvement of
      DPIV/CD26 in early phosphorylation mechanisms which are known to be essential in
      the signal transduction cascade of human T lymphocytes. We have found that DPIV
      specific inhibitors (Lys[Z(NO2)]-thiazolidide and -piperidide) are capable of
      inducing intracellular tyrosine phosphorylation in resting human T cells. On the
      other hand, both inhibitors decreased the PMA-induced tyrosine phosphorylation in
      human T cells in a dose-dependent manner. Furthermore, a linkage between CD26 and
      the tyrosine kinase p56(lck) was shown by inhibition of PMA-induced
      hyperphosphorylation of p56(lck) by means of DPIV-specific inhibitors. The data
      presented here suggest that the inhibition of DPIV enzymatic activity induces a
      inhibitory signal transmitted by tyrosine kinases which leads to a block in a PMA
      induced downstream pathway. These results support the assumption that DPIV/CD26
      is directly involved in early processes of T cell activation via its enzymatic
      activity.

PMID- 9758696
TI  - The impact of variation in the number of CD8(+) T-cell precursors on the outcome
      of virus infection.
AB  - We investigated the role of varying the initial number of naive antiviral CTL
      precursors on the dynamics of LCMV-DOCILE infection. C57BL/6 mice, exhibiting
      LCMV-specific CTLp frequencies of about 50, are protected against virus
      persistence over a range of infectious doses up to 10(4) pfu. With 10-fold higher
      doses, a 100-fold increase in CTLp is required to restore virus control. With
      doses above 10(6) pfu, elevation of the initial CTLp number leads only to lethal
      immunopathology. Similarly, a 1000-fold increase in the number of initial naive
      CTLp enhances the overall kinetics of virus elimination, but cannot limit early
      virus spread within the first 48 h after low-dose infection (500 pfu). Increases
      in initial naive virus-specific CTLp numbers are of limited benefit in antiviral
      control. In addition to the number of virus-specific T cells, the time period
      needed to reach cytolytic effector function is a limiting parameter.

PMID- 9758697
TI  - Macrophages may activate or destroy T cells with which they form antigen- or
      coreceptor-mediated cellular conjugates.
AB  - The formation of antigen- or mitogen-mediated cellular conjugates with T cells
      enables macrophages to trigger in T cells costimulatory signals and to facilitate
      T cell clonal expansion and differentiation. The present study describes T cell
      death as an alternative consequence of T cell interaction with macrophages.
      Macrophages initiate the deletion of T cells which they target for conjugate
      formation through CD4 coreceptors. After suboptimal engagement, the TCR mediates
      a deletion program. Optimal TCR stimulation induces a rescue program which
      overrides the deletion program induced by suboptimal antigen receptor ligation or
      by coreceptor engagement. Evidence is presented suggesting that receptor
      clustering favors the transmission of activation signals, whereas ligation of
      nonclustered receptors facilitates T cell deletion.

PMID- 9758699
TI  - MAP kinase inactivation is required only for G2-M phase transition in early
      embryogenesis cell cycles of the starfishes Marthasterias glacialis and
      Astropecten aranciacus.
AB  - Downregulation of MAP kinase is a universal consequence of fertilization in the
      animal kingdom. Here we show that oocytes of the starfishes Astropecten
      aranciacus and Marthasterias glacialis complete meiotic maturation and form a
      pronucleus when treated with 1-methyladenine and then complete DNA replication
      and arrest at G2 if not fertilized. Release of G2 by fertilization or a variety
      of parthenogenetic treatments is associated with inactivation of MAP kinase.
      Prevention of MAP kinase inactivation by microinjection of Ste11-DeltaN, a
      constitutively active budding yeast MAP kinase kinase kinase, arrests fertilized
      eggs at G2 in either the first or the second mitotic cell cycle, in a dose
      dependent manner. G1 arrest is never observed. Conversely, inactivation of MAP
      kinase by microinjection of the MAP kinase-specific phosphatase Pyst-1 releases
      mature starfish oocytes from G2 arrest. The role of MAP kinase in arresting cell
      cycle at various stages in oocytes of different animal species is discussed.

PMID- 9758700
TI  - The relationship between rhombomeres and vestibular neuron populations as
      assessed in quail-chicken chimeras.
AB  - The aim of this study was to evaluate the role segmentation plays in the
      determination of neuronal identity in the hindbrain. We focused on two specific
      sets of hindbrain neurons, namely, the vestibulospinal and vestibulo-ocular
      neurons, which comprise distinct groups that can be identified and distinguished
      by virtue of their axonal projection pathways. The relationship between
      rhombomeres and the vestibular neuron groups was assessed by a combination of
      quail-chicken chimeric grafting and selective retrograde axonal tracing.
      Individual quail hemirhombomeres were transplanted homotopically and
      isochronically into a chicken embryo host. Subsequently, vestibulospinal and
      vestibulo-ocular neurons with specific axon trajectories were labeled
      retrogradely with biotin-conjugated dextran-amines. The relationship between the
      spatial domains of the vestibular neuron groups and rhombomere-derived domains
      had the following features: (1) some groups were derived from single rhombomeres;
      (2) some groups were derived from multiple contiguous rhombomeres; (3) two groups
      occupied domains that could not be defined in terms of whole rhombomere lengths;
      (4) some groups spanning multiple rhombomeres exhibited an internal
      cytoarchitectonic organization that related to individual rhombomeres; and (5)
      some groups exhibited limited boundary violation. These results support the
      notion that positional information within defined domains of the neural tube
      provides a groundplan for the regional determination of neuronal identity and
      axon pathfinding, and that hindbrain segmentation contributes to this process.
      But they also indicate that segmentation is not the only mechanism that defines
      the rostrocaudal domains of neuron types. Moreover, they emphasize that the
      relationship between rhombomeres and neuronal determination cannot be couched
      simply in terms of segmental iteration or of bimeric (paired rule) specification.

PMID- 9758701
TI  - The alpha4 subunit of integrin is important for neural crest cell migration.
AB  - We identify the alpha4 subunit of integrin as a predominant integrin expressed by
      neural crest cells in both avian and murine embryos. Using degenerate primers, we
      obtained a PCR fragment of the chick integrin alpha4 subunit that was
      subsequently used to clone the full-length subunit with a predicted amino acid
      sequence 60% identical to human and mouse alpha4 subunits. In situ hybridization
      demonstrates that chick integrin alpha4 mRNA is expressed at high levels by
      migrating neural crest cells and neural crest-derived ganglia at both cranial and
      trunk levels. An antibody against the murine alpha4 subunit revealed similar
      distribution patterns in mouse to chick. In addition to neural crest cells, the
      integrin alpha4 subunit was later observed on the muscle masses of the limb, the
      apical ectodermal ridge, and the developing liver. To examine the functional role
      of the integrin alpha4 subunit in neural crest cell migration, we used an explant
      preparation that allows visualization of neural crest cells in their normal
      environment with or without perturbing reagents. In the presence of a blocking
      antibody against the mouse integrin alpha4 subunit, there was a profound
      abrogation of neural crest cell migration at trunk and hindbrain levels. Both the
      numbers of migrating neural crest cells and the total distance traversed were
      markedly reduced. Similarly, avian embryos injected with synthetic peptides that
      contain the integrin alpha4 binding site in fibronectin displayed abnormal neural
      crest cell migration. Our results suggest that the integrin alpha4 subunit is
      important for normal neural crest cell migration and may be one of the primary
      alpha subunits used for neural crest cell migration in vivo. Furthermore, the
      integrin alpha4 subunit represents a useful neural crest marker in the mouse.

PMID- 9758702
TI  - Roles of transforming growth factor-alpha and epidermal growth factor in chick
      limb development.
AB  - We have examined the distribution of transforming growth factor-alpha (TGF
      alpha), epidermal growth factor (EGF), and the chicken EGF receptor (c-erbB), in
      embryonic chick limbs. Prior to limb budding, TGF-alpha is present in prospective
      limb-forming mesoderm and in prospective apical ectodermal ridge (AER)-forming
      ectoderm, but is not detected in non-limb-forming flank mesoderm or ectoderm, nor
      in presumptive non-AER-forming limb ectoderm, suggesting possible roles in
      initial limb formation and AER induction. Consistent with this possibility, TGF
      alpha is present in the mesoderm of the wing buds of the amelic chick mutants
      limbless and wingless, which form and bud normally, but is absent from limbless
      and wingless ectoderm, which fails to form an AER. TGF-alpha and EGF are present
      in the AER of the developing limb, and TGF-alpha, EGF, and c-erbB are present in
      the underlying subridge mesoderm, suggesting possible roles in reciprocal
      AER/subridge mesoderm interactions required for limb outgrowth. We found that
      exogenous TGF-alpha and EGF can promote the outgrowth of limb mesoderm in the
      absence of the AER in vitro and can also promote the outgrowth of limbless and
      wingless wing bud explants. EGF is present in ventral but not dorsal limb
      ectoderm, suggesting a role for EGF in specification of ventral ectoderm. TGF
      alpha and EGF are not detected in the differentiating cartilaginous elements or
      muscle primordia of the limb, suggesting that cessation of TGF-alpha and EGF
      expression may be required for cartilage and muscle formation. We have found that
      exogenous TGF-alpha and EGF inhibit chondrogenesis and myogenesis of limb
      mesenchyme in vitro. Together these results indicate that signaling through the
      EGF receptor via endogenous TGF-alpha and EGF may be important for initial limb
      formation, AER induction, outgrowth of limb mesoderm, and regulation of limb
      chondrogenic and myogenic differentiation.

PMID- 9758703
TI  - The Cspg2 gene, disrupted in the hdf mutant, is required for right cardiac
      chamber and endocardial cushion formation.
AB  - The heart defect (hdf) mouse is a recessive lethal that arose from a transgene
      insertional mutation on chromosome 13. Embryos homozygous for the transgene die
      in utero by embryonic day 10.5 postcoitus and exhibit specific defects along the
      anterior-posterior cardiac axis. The future right ventricle and conus/truncus of
      the single heart tube fail to form and the endocardial cushions in the
      atrioventricular and conus/truncus regions are absent. Because the hdf mouse
      mutation provided the opportunity to identify a gene required for endocardial
      cushion formation and for specification or maintenance of the anterior most
      segments of the heart, we initiated studies to further characterize the
      phenotype, clone the insertion site, and identify the gene disrupted. Chromosome
      mapping studies first identified the gene, Cspg2 (versican), as a candidate hdf
      gene. In addition, an antibody recognizing a glycosaminoglycan epitope on
      versican was found to be positive by immunohistochemistry in the extracellular
      matrix of normal wild-type embryonic hearts, but absent in homozygous hearts.
      Expression analysis of the Cspg2 gene showed that the 6/8, 6/9, and 7/9 Cspg2
      exon boundaries were present in mRNA of normal wild-type embryonic hearts but
      absent in the homozygous mutant embryos. DNA sequence flanking the transgene was
      used to isolate from a normal mouse library overlapping genomic DNA segments that
      span the transgene insertion site. The contiguous genomic DNA segment was found
      to contain exon 7 of the Cspg2 in a position 3' to the transgene insertion site.
      These four separate lines of evidence support the hypothesis that Cspg2 is the
      gene disrupted by the transgene insertion in the hdf mouse line. The findings of
      this study and our previous studies of the hdf insertional mutant mouse have
      shown that normal expression of the Cspg2 gene is required for the successful
      development of the endocardial cushion swellings and the embryonic heart segments
      that give rise to the right ventricle and conus/truncus in the outlet of the
      looped heart.

PMID- 9758704
TI  - A single rostrocaudal colonization of the rodent intestine by enteric neuron
      precursors is revealed by the expression of Phox2b, Ret, and p75 and by explants
      grown under the kidney capsule or in organ culture.
AB  - The colonization of the rodent gastrointestinal tract by enteric neuron
      precursors is controversial due to the lack of specific cellular markers at early
      stages. The transcription factor, Phox2b, is expressed by enteric neuron
      precursors (Pattyn et al. Development 124, 4065-4075, 1997). In this study, we
      have used an antiserum to Phox2b to characterize in detail the spatiotemporal
      expression of Phox2b in the gastrointestinal tract of adult mice and embryonic
      mice and rats. In adult mice, all enteric neurons (labeled with neuron-specific
      enolase antibodies), and a subpopulation of glial cells (labeled with GFAP
      antibodies), showed immunoreactivity to Phox2b. In embryonic mice, the appearance
      of Phox2b-immunoreactive cells was mapped during development of the
      gastrointestinal tract. At Embryonic Days 9.5-10 (E9.5-10), Phox2b-labeled cells
      were present only in the stomach, and during subsequent development, labeled
      cells appeared as a single rostrocaudal wave along the gastrointestinal tract; at
      E14 Phox2b-labeled cells were present along the entire length of the
      gastrointestinal tract. Ret and p75 have also been reported to label migratory
      stage enteric neuron precursors. A unidirectional, rostral-to-caudal colonization
      of the gastrointestinal tract of embryonic mice by Ret- and p75-immunoreactive
      cells was also observed, and the locations of Ret- and p75-positive cells within
      the gut were very similar to that of Phox2b-positive cells. To verify the
      location of enteric neuron precursors within the gut, explants from
      spatiotemporally defined regions of embryonic intestine, 0.3-3 mm long, were
      grown in the kidney subcapsular space, or in catenary organ culture, and examined
      for the presence of neurons. The location and sequence of appearance of enteric
      neuron precursors deduced from the explants grown under the kidney capsule or in
      organ culture was very similar to that seen with the Phox2b, Ret, and p75
      antisera. Previous studies have mapped the rostrocaudal colonization of the rat
      intestine by enteric neuron precursors using HNK-1 as a marker. In the current
      study, all HNK-1-labeled cells in the gastrointestinal tract of rat embryos
      showed immunoreactivity to Phox2b, but HNK-1 cells comprised only a small
      subpopulation of the Phox2b-labeled cells. In addition, in rats, Phox2b-labeled
      cells were present in advance of (more caudal to) the most caudal HNK-1-labeled
      cells by 600-700 microm in the hindgut at E15. We conclude that the neural crest
      cell population that arises from the vagal level of the neural axis and that
      populates the stomach, midgut, and hindgut expresses Phox2b, Ret, and p75. In
      contrast, the sacral-level neural crest cells that populate the hindgut either do
      not express, or show a delayed expression of, all of the known markers of vagal-
      and trunk-level neural crest cells.

PMID- 9758705
TI  - N-cadherin/catenin-mediated morphoregulation of somite formation.
AB  - Somitogenesis during early stages in the chick and mouse embryo was examined in
      relation to N-cadherin-mediated adhesion. Previous studies indicated that N
      cadherin localizes to the somite regions during their formation. Those
      observations were extended to include a spatiotemporal immunohistochemical
      analyses of beta-catenin and alpha-catenin, as well as a more detailed study of N
      cadherin, during segmentation, compaction, and compartmentalization of the
      somite. N-cadherin and the catenins appear early within the segmental plate and
      are expressed as small patch-like foci throughout this tissue. The small foci of
      immunostaining coalesce into larger clusters of N-cadherin/catenin-expressing
      regions. The clusters subsequently coalesce into a region of centrally localized
      cells that express N-cadherin/catenins at their apical surfaces. The multiple
      clusters are spaced wide apart in the anterior segmental plates that form the
      first 6 somite pairs, as contrasted to segmental plates that form somites 7 and
      beyond. To examine the functional significance of N-cadherin, segmental plates
      were exposed to antibodies that perturb N-cadherin-mediated adhesion in the chick
      embryo. The multiple, anomalous somites that result in these experiments indicate
      that each N-cadherin/catenin-expressing cluster can give rise to a somitic
      structure. beta-Catenin involvement in somitogenesis suggests a role for Wnt
      mediated signaling. Embryos treated with LiCl also show induction of similar
      anomalous somites indicating further the possibility that Wnt-mediated signaling
      may be involved in the clustering event. It is suggested that beta-catenin serves
      to initiate the adhesion process which is spread then by N-cadherin. Later during
      compartmentalization, N-cadherin/catenins remain expressed by the myotome
      compartment. Taken together, these results suggest that the Ca2+-dependent cell
      adhesion molecule N-cadherin and the intracellular catenins are important in
      segmentation and formation of the somite and myotome compartment. It is proposed
      that the N-cadherin-mediated adhesion process may serve as a common,
      evolutionarily conserved, link in the differentiation pathways of skeletal and
      cardiac muscle.

PMID- 9758706
TI  - Precocious expression of the Wilms' tumor gene xWT1 inhibits embryonic kidney
      development in Xenopus laevis.
AB  - The tumor suppressor WT1 has been demonstrated to have a wide variety of
      activities in vitro and is required for metanephric development in vivo. In the
      experiments presented here, the Xenopus pronephros was used as a simple model
      system to examine the activity of Xenopus WT1 (xWT1) during kidney development.
      xWT1 was ectopically expressed in Xenopus embryos by mRNA injection and found to
      inhibit pronephric tubule development. Confocal microscopy confirmed this
      observation and revealed that the inhibition was the result of a failure to form
      a pronephric anlage of appropriate size rather than a defect in
      epithelialization. Examination of Xlim-1 expression, an early molecular marker of
      pronephric specification, in tailbud embryos indicated that injected xWT1 mRNA
      inhibited pronephric specification prior to any overt sign of morphogenesis
      (Xenopus stage 21). These results suggest that xWT1 may act to repress tubule
      specific gene expression in the portion of the pronephros fated to form its
      vascular structure, the glomus.

PMID- 9758707
TI  - Voltage-dependent activation of frog eggs by a sperm surface disintegrin peptide.
AB  - Fertilin, a sperm protein of the metalloprotease/disintegrin/cysteine-rich (MDC)
      family, plays a critical role in sperm-egg binding in mammals. Peptides
      corresponding to the disintegrin domain of fertilin and antibodies against
      fertilin have been shown to inhibit mammalian sperm-egg binding and fusion. A
      protein from the same family, xMDC16, was recently cloned from frog (Xenopus
      laevis) testis and was found to be involved in frog sperm-egg binding. Here we
      report that xMDC16 is localized predominantly on the posterior surface of egg
      jelly-activated sperm, and peptides from the disintegrin domain of this protein
      activate eggs when applied near the egg surface. Egg activation was dependent on
      (1) specific amino acid residues (KTX); (2) the presence of divalent cations, but
      not external Ca2+ alone; and (3) voltage across the egg plasma membrane. This is
      the first demonstration of egg activation in vertebrates by the surface
      application of a peptide derived from a sperm surface protein, supporting a model
      for egg activation that involves a signal transducing receptor for sperm in the
      egg's plasma membrane.

PMID- 9758708
TI  - A novel alternative spliced variant of the transcription factor AP2alpha is
      expressed in the murine ocular lens.
AB  - The AP2alpha gene encodes a transcription factor containing a basic, helix-span
      helix DNA-binding/dimerization domain, which is developmentally regulated and
      retinoic acid inducible. Recent reports about AP2alpha null mice indicate that
      AP2alpha plays an important role in embryogenesis, especially in craniofacial
      development and midline fusion. Ocular development is also affected in these null
      mice. As AP2alpha may be involved in transcriptional regulation in the lens, it
      was important to examine the expression of the AP2alpha gene in the lens. Four
      AP2alpha mRNA variants have been previously isolated from whole mouse embryos.
      Variants 1, 3, and 4 are transcriptional activators that are transcribed from
      different promoters and variant 2 is a repressor lacking the activation domain
      encoded by exon 2. Using in situ-PCR, we found that AP2alpha is expressed in the
      lens epithelia but not in the lens fibers. RT-PCR analysis of lens mRNA with
      amplimers specific for each variant revealed that AP2alpha variants 1, 2, and 3
      are expressed in newborn mouse lenses. However, variant 4 is not expressed in the
      lens. In this report we characterized a novel isoform, which we named variant 5,
      expressed in the lens and kidney. Variant 5, which is generated by alternative
      splicing, may function as a repressor due to the partial deletion of the proline
      rich transactivation domain encoded by exon 2. This is the first molecular
      characterization of AP2alpha gene expression in the lens. Our results indicate
      that two activator and two repressor AP2alpha isoforms may play a role in
      regulating gene expression in the lens.

PMID- 9758709
TI  - Identification of gametophytic mutations affecting female gametophyte development
      in Arabidopsis.
AB  - The female gametophyte (embryo sac or megagametophyte) plays a critical role in
      sexual reproduction of angiosperms. It is the structure that produces the egg
      cell and central cell which, following fertilization, give rise to the seed's
      embryo and endosperm, respectively. In addition, the female gametophyte mediates
      a host of reproductive processes including pollen tube guidance, fertilization,
      and the induction of seed development. Several major events occur during
      megagametogenesis, including syncitial nuclear divisions, cellularization,
      nuclear migration and fusion, and cell death. While these events have been
      described morphologically, the molecules regulating them in the female
      gametophyte are largely unknown. We discuss a genetic screen based on reduced
      seed set and segregation distortion to identify mutations affecting
      megagametogenesis and female gametophyte function. We report on the isolation of
      four mutants (fem1, fem2, fem3, and fem4) and show that the four mutations map to
      different locations within the genome. Additionally, we show that the fem1 and
      fem2 mutations affect only the female gametophyte, while the fem3 and fem4
      mutations affect both the female and male gametophyte. We analyzed female
      gametophyte development in these four mutants as well as in the gfa2, gfa3, gfa4,
      gfa5, and gfa7 mutants. We found that the fem2, fem3, gfa4, and gfa5 mutants
      abort development at the one-nucleate stage, while the fem1, fem4, gfa2, gfa3,
      and gfa7 mutants are affected in processes later in development such as polar
      nuclei fusion and cellularization. The establishment of a genetic screen to
      identify mutants and the development of a rapid procedure for analyzing mutant
      phenotypes represent a first step in the isolation of molecules that regulate
      female gametophyte development and function.

PMID- 9758710
TI  - Volume 92, number 2 (1997), in article no. DB978773, "Localized maternal proteins
      in xenopus revealed by subtractive Immunization," by james M. Denegre, erich R.
      Ludwig, and kimberly L. Mowry, pages 446-454 

PMID- 9758711
TI  - Regulation and function of pulmonary surfactant protein B.
AB  - Pulmonary surfactant, a complex mixture of phospholipids and specific associated
      proteins, reduces the surface tension at the air-liquid interface of the distal
      conducting airways and gas exchanging alveoli of the lung. Lipids, primarily
      neutral and phospholipids, compose approximately 90% of the surfactant complex.
      The remaining 10% of surfactant is composed of at least three surfactant-specific
      proteins, designated surfactant protein A (SP-A), SP-B, and SP-C. These proteins
      contribute to the formation, stabilization, and function of organized surfactant
      structures. This article briefly reviews the normal composition and function of
      pulmonary surfactant and specifically reviews the structure, function, and
      regulation of surfactant protein B (SP-B). The recent identification of neonates
      with refractory respiratory failure due to a genetic absence of SP-B and the
      study of transgenic mice in which SP-B gene expression has been ablated highlight
      the importance of the protein to surfactant function, synthesis, and metabolism
      and to the maintenance of lung function. Gene reconstitution experiments in vitro
      and in SP-B-deficient transgenic mice suggest specific functions for the amino
      and carboxyl terminal domains of the protein. SP-B deficiency is a potential
      target for gene therapy in human patients.

PMID- 9758712
TI  - Identification of four novel mutations in patients with carnitine
      palmitoyltransferase II (CPT II) deficiency.
AB  - Carnitine palmitoyltransferase II (CPT II) deficiency, an autosomal recessive
      disorder of fatty-acid oxidation, presents as three distinct phenotypes
      (neonatal, infantile, and adult onset). In order to investigate the molecular
      basis of these three phenotypes, six patients with CPT II deficiency have been
      studied. All six unrelated patients in this study experienced the clinical
      symptoms of CPT II deficiency. Three patients had the neonatal form, one had the
      milder infantile form, and the remaining two had the adult-onset form with
      "muscular" symptoms only. Their diagnoses were based upon in vitro analysis of
      the mitochondrial beta-oxidation pathway in fibroblasts and standard enzyme
      assays. We devised a method to screen the entire coding sequence and flanking
      splice junction of the CPT II gene. A total of six different mutations have been
      identified, including four novel mutations. Among them, the previously reported
      common mutation, S113L, was only found in 3 of 12 variant alleles. Three of the
      six mutations have been identified in a few unrelated patients, while the
      remaining three have been found in single families. This study, as well as those
      by others, indicates genetic heterogeneity in this disease. In addition to
      tabulating the mutations, the correlation of mutant genotype to clinical
      phenotype is briefly discussed.

PMID- 9758713
TI  - A randomized clinical trial of topical cysteamine disulfide (cystamine) versus
      free thiol (cysteamine) in the treatment of corneal cystine crystals in
      cystinosis.
AB  - In nephropathic cystinosis, corneal cystine crystals cause severe photophobia and
      corneal erosions. Topical cysteamine dissolves these crystals, but cannot be
      marketed because it rapidly oxidizes to the disulfide form, cystamine, at room
      temperature. Since cystamine itself could be used commercially, we compared the
      efficacy of cystamine and cysteamine with respect to cystine crystal dissolution
      in a randomized, double-masked clinical trial. One eye each of 14 patients with
      cystinosis was randomized to either cystamine or cysteamine, 0.5%, with 0.01%
      benzalkonium chloride; the companion eye was treated with the alternate
      preparation. Corneal crystals were photographed and a density score was assigned
      to each slide based on 13 standard slides. After 8-20 months, 6 patients showed
      significant reduction of the corneal crystal score in only one eye. In each case,
      the improved eye was the cysteamine-treated eye. Theoretically, cysteamine should
      dissolve both intracellular and extracellular crystals, whereas cystamine should
      dissolve only intracellular crystals because it must first be reduced to the free
      thiol by the cytoplasmic-reducing environment. Hence, the lack of efficacy of the
      disulfide cystamine suggests that some corneal cystine crystals in cystinosis
      patients are extracellular, and that another form of stable, topical cysteamine
      must be developed for cystinosis patients.

PMID- 9758715
TI  - Deficiency of biotinyl-AMP synthetase activity in fibroblasts of patients with
      holocarboxylase synthetase deficiency.
AB  - A simple, rapid assay was developed to diagnose holocarboxylase synthetase
      deficiency. Holocarboxylase synthetase first catalyzes the formation of biotinyl
      AMP from biotin and ATP, an activity designated as biotinyl-AMP synthetase. In
      the second step of the reaction, biotin is transferred from biotinyl-AMP to the
      enzymatically inactive apocarboxylase to form an active holocarboxylase. The
      assay for holocarboxylase synthetase activity therefore requires a protein
      apocarboxylase substrate which is not readily available. In the assay for
      biotinyl-AMP synthetase, hydroxylamine reacts nonenzymatically with the product
      of the enzymatic reaction, biotinyl-AMP, to form biotinylhydroxamate. At the end
      of the reaction, unreacted radioactive biotin substrate, which is negatively
      charged at neutral pH, is bound to an anion-exchange resin and a neutral
      radioactive biotinylhydroxamate product in the supernatant is counted. In
      fibroblasts from 11 patients with proven holocarboxylase synthetase deficiency,
      the mean biotinyl-AMP synthetase activity at 25 nM biotin was 4% of the control
      mean with a range of 0.2 to 8%. This is an improved assay because it does not
      require preparation of an apocarboxylase substrate and is suitable for the
      diagnosis of patients with holocarboxylase synthetase deficiency.

PMID- 9758714
TI  - Molecular basis of hyperargininemia: structure-function consequences of mutations
      in human liver arginase.
AB  - Hyperargininemia is a rare autosomal recessive disorder that results from a
      deficiency of hepatic type I arginase. At the genetic level, this deficiency in
      arginase activity is a consequence of random point mutations throughout the gene
      that lead to premature termination of the protein or to substitution mutations.
      Given the high degree of sequence homology between human liver and rat liver
      enzymes, we have mapped both patient and nonpatient mutations of the human enzyme
      onto the structure of the rat liver enzyme to rationalize the molecular basis for
      the low activities of these mutant arginases. Mutations identified in
      hyperargininemia patients affect the structure and function of the enzyme by
      compromising active-site residues, packing interactions in the protein
      scaffolding, and/or quaternary structure by destabilizing the assembly of the
      arginase trimer.

PMID- 9758716
TI  - Genetic heterogeneity of adrenocorticotropin (ACTH) resistance syndromes:
      identification of a novel mutation of the ACTH receptor gene in hereditary
      glucocorticoid deficiency.
AB  - Hereditary primary adrenal insufficiency syndromes due to ACTH resistance include
      hereditary glucocorticoid deficiency (HGD) and Allgrove's syndrome (AS). Patients
      with both conditions present in childhood with failure to thrive, weakness, and
      fatigue or adrenal crisis; patients with AS in addition have alacrima and
      achalasia (triple A syndrome). We studied four kindreds with HGD and four
      kindreds with AS for abnormalities of the ACTH receptor (ACTHR) gene. The ACTHR
      coding sequence in all AS kindreds and two HGD kindreds was normal. Analysis of
      the ACTHR gene of the proband in one of the HGD kindreds showed him to be
      homozygous for the previously described G221T transition causing a Ser74Ile
      substitution of the protein, which has been shown to inactivate the ACTHR in
      signal transduction. The proband in another HGD kindred was found to be a
      compound heterozygote with the G221T transition in one allele and a novel C818A
      transition in the other allele of ACTHR. The C818A transition caused the
      substitution of the highly conserved Pro273 by His in the receptor protein. In
      vitro expression of the mutated ACTHR in mouse melanoma M3 cells showed that at a
      medium ACTH concentration of 3 nM, cells transfected with the wild-type ACTHR
      produced twofold and threefold, respectively, of the amount of intracellular cAMP
      when compared to cells transfected with the ACTHR carrying the Pro273His and the
      Ser74Ile mutation, respectively, confirming that HGD in this kindred is caused by
      loss-of-function mutations of the ACTHR. These results showed that the genetic
      cause of the ACTH-resistant syndromes is heterogeneous.

PMID- 9758717
TI  - PCR-based methods for identifying genetic variations in human alpha1B- and beta2
      adrenergic receptors.
AB  - alpha- and beta-adrenergic receptors belong to the superfamily of G-protein
      coupled, seven transmembrane domain receptors and regulate a variety of cellular
      processes. Previous studies have demonstrated that changes in the amino acid
      sequence can result in substantial changes in the function of the receptors and
      it has been suggested that there may be an association between different disease
      states and the altered structure of alpha- and beta-adrenergic receptors.
      Accordingly, we have developed a simple PCR method for the identification of
      polymorphisms in the coding sequences of the human beta2-adrenergic receptor and
      the alpha1B-adrenergic receptor. This method may be useful for screening
      individual patients or at-risk populations for endocrine-metabolic disorders, as
      well as for asthma, cardiovascular disorders, and neuropsychiatric diseases.

PMID- 9758718
TI  - Differential gene expression in apoptosis: identification of ribosomal protein
      23K, a cell proliferation inhibitor.
AB  - Gene expression during the camptothecin-induced apoptotic death of human leukemic
      U937 cells and mouse T-cell hybridoma QW4.1 cells was studied by the mRNA
      differential display technique. Ten clones were confirmed to be differentially
      expressed, nine of which encoded novel sequences. One clone, U3.2, was induced
      approximately 10-fold in camptothecin-treated cells and was found to be identical
      to a highly basic 23-kDa human protein which contains basic leucine zipper-like
      motifs and has recently been identified as the human homologue of the rat
      ribosomal protein L13a. Northern blot analysis revealed a major mRNA of
      approximately 0.9 kb and a minor mRNA of approximately 1.3 kb. Overexpression of
      a full-length 23K cDNA, tagged with a FLAG sequence, in COS-7 cells revealed a
      predominantly nucleolar localization and the absence of any 23K protein from the
      cytoplasm. Subsequent transfection studies, using antisense phosphorothioate
      modified oligonucleotides, revealed that inhibition of 23K expression results in
      an increased cell proliferation and greater sensitivity of U937 cells to the
      effects of camptothecin-induced cell death. Upregulation of 23K expression using
      a cDNA construct resulted in a decrease in cell proliferation and growth arrest,
      suggesting a role for 23K protein as a proliferation checkpoint following a
      cellular insult.

PMID- 9758719
TI  - Structural specificity of serotonin effect on human erythrocyte fragility.
AB  - Serotonin, a neurotransmitter and vasoconstrictor, affects various cell
      properties. We have analyzed the importance of its structural components for its
      extensive effect on human erythrocyte fragility, using its O- and N-linked
      derivatives and related compounds. The results presented in this communication
      indicate that the amino group, free of adjacent negative charges, and the
      hydroxyl group are indispensable for the serotonin-induced increase in red blood
      cell fragility.

PMID- 9758721
TI  - Alteration of the intestinal intraepithelial lymphocytes during total parenteral
      nutrition.
AB  - Total parenteral nutrition (TPN) may cause increased rates of bacterial
      translocation (BT), possibly due to a loss of epithelial integrity. Cultured
      epithelial cells have been shown to lose tight junction integrity with interferon
      gamma (INF-gamma) an action which may be blocked by transforming growth factor
      beta (TGF-beta). Because intraepithelial lymphocytes (IEL) are a rich source of
      these cytokines in the epithelium, we hypothesized that changes in the IEL, while
      mice were receiving TPN, may be responsible for the mediation of such cytokine
      responses. C57BL/6 mice were randomized to a Control group which received
      intravenous saline and mouse chow, or a TPN group which received intravenous TPN
      with no oral feeding. At 7 days mice were assessed for BT. Isolated IEL were
      stained for CD4, CD8, and CD44 (as a marker for memory T-cells) and flow
      cytometry was performed. mRNA was extracted from remaining IEL for cytokine
      expression. Reverse transcriptase polymerase chain reaction was performed to
      detect TGF-beta1 and INF-gamma mRNA expression. Densities were standardized to
      beta-actin expression. The incidence of BT to mesenteric lymph nodes was 40 and
      12.5%, for the TPN and Control groups, respectively. TPN led to statistically
      significant decreases in the CD4+, CD8-; CD4+, CD8+; and the CD8+, CD44+ IEL
      subpopulations (P < 0.05). mRNA expression for INF-gamma was increased by 53% (P
      < 0.05), and TGF-beta1 mRNA expression was decreased by 75% (P = 0.1) in the IEL
      of TPN mice when compared with Controls. TPN led to significant changes in the
      IEL. Such alterations of the IEL phenotype and function may be a critical
      mechanism by which epithelial integrity is lost.

PMID- 9758720
TI  - Carrier frequency of the Bloom syndrome blmAsh mutation in the Ashkenazi Jewish
      population.
AB  - Bloom syndrome is more common in individuals of Ashkenazi Jewish descent than in
      any other population, and one particular mutation in the Bloom syndrome gene,
      blmAsh, is homozygous in nearly all Ashkenazi Jewish persons with Bloom syndrome.
      We have determined the frequency of blmAsh in 1491 Ashkenazi Jewish persons with
      no known history of Bloom syndrome and found that 1 in 107 persons was
      heterozygous. Although not common, genetic screening for Bloom syndrome is
      feasible in this population.

PMID- 9758722
TI  - The basis for progesterone impairment of gallbladder contractility in male guinea
      pigs in vitro.
AB  - Progesterone suppresses gallbladder smooth muscle function but its exact
      mechanism is unknown. We sought to determine the cellular site where progesterone
      impairs gallbladder smooth muscle. Sixty-four adult male guinea pigs were
      injected with either progesterone (2 mg/kg/day sc) or normal saline (controls)
      for 7 days. Dose-response curves of gallbladder strips to cholecystokinin (CCK),
      bethanechol, and potassium (K+) were constructed in vitro. To better define the
      basis for the progesterone effect, gallbladder contractile response was
      determined to specific agonists: aluminum fluoride and mastoparan (direct G
      protein activators), cyclopiazonic acid (CPA), and a calcium ionophore (A-23187).
      Gallbladder from animals on progesterone exhibited a marked decrease in
      contractile response to CCK and bethanechol compared with controls (P < 0.05).
      Further, gallbladder contraction remained depressed (P < 0.05) in progesterone
      treated animals, when the G protein was directly activated with aluminum fluoride
      and mastoparan. In contrast, the responses to K+ (acting independent of receptor
      G-protein) and to A-23187 and CPA (agonists that bypassed the membrane) were
      comparable in both groups (NS). It is concluded that progesterone directly
      inhibits gallbladder smooth muscle contractility in vitro to a standard hormone,
      CCK, and a cholinergic agent. Such depressed contraction is not due to an altered
      contractile machinery, since it is normal with agonists that act independently of
      G-protein activation. Progesterone thus interferes with signaling through the G
      protein, either by directly becoming closely associated with the cell membrane or
      by indirectly perturbing its receptor products.

PMID- 9758723
TI  - Early gene expression associated with regeneration is intact after massive
      hepatectomy in rats.
AB  - BACKGROUND: Liver regeneration occurs promptly after partial hepatectomy,
      although the factors regulating this response have not been fully clarified.
      Molecular events in the regenerative response have been widely characterized
      after 70% hepatectomy which represents a model of "normal" liver regeneration in
      rats. More extensive resection results in hepatic failure which has been
      attributed to a critical loss of hepatic mass. It is not known whether the
      pattern of genes expressed early in regeneration remains intact after lethal
      hepatectomy. We hypothesize that the increased expression of selected early
      response genes remains intact after massive hepatectomy. The aim of this study
      was to compare the expression of selected genes after 70 and 85% hepatectomy.
      MATERIALS AND METHODS: One hundred ten Wistar rats were divided into three
      groups: control group (sham laparotomy) (n = 30), 70% hepatectomy group (n = 40),
      and 85% hepatectomy group (n = 40). Animals were sacrificed at intervals. Livers
      were excised and divided into four equal specimens, snap frozen, and stored at 
      70 degrees C. RNA was extracted by standard methods and preparations were probed
      for protooncogenes, c-myc, c-fos, and for hepatocyte growth factor, and its
      receptor, c-met. After overnight exposure of autoradiographs, quantification was
      accomplished by densitometry of RNA slot blots. RESULTS: After 70% hepatectomy,
      peaks of maximal expression for both c-myc and c-met were observed after 1 and 12
      h. For c-fos, peak of maximal expression was observed at 6 h. For HGF, peak was
      observed between 12 h and Day 2. After 85% hepatectomy, rats demonstrated similar
      patterns including peak expression of c-myc at 1 h, but altered peak at 12 h. For
      c-met, the same pattern was observed between 1 and 12 h. For HGF, two peaks were
      noted: a first peak at 1 h, and a peak similar to the peak observed after 70%
      hepatectomy at 12 h. CONCLUSIONS: These results suggest that early molecular
      events which are part of the regenerative response are largely intact after 85%
      lethal hepatectomy. We propose that liver dysfunction and the failure of
      regeneration observed after 85% hepatectomy is not due to alteration of early
      signaling. Further study will be required to define failure of the regeneration
      program in this model.

PMID- 9758724
TI  - Vasopressin antagonist improves renal function in a rat model of
      pneumoperitoneum.
AB  - Pneumoperitoneum (PP) is associated with oliguria and increased plasma arginine
      vasopressin (AVP) levels. This study investigated the role of AVP in the
      pathogenesis of oliguria due to PP. Anesthetized and ventilated rats (n = 12)
      were subjected for 1 h to carbon dioxide PP with an intra-abdominal pressure of 8
      mmHg or, as control, at 0 mmHg, before the determination of plasma AVP level.
      Another group of rats (n = 48) subjected to PP or control conditions was
      pretreated with the AVP V2 receptor antagonist, OPC-31260 (5 mg/kg), or vehicle,
      and their renal parameters were measured. Glomerular filtration rate (GFR) was
      determined by inulin clearance in an additional group of rats (n = 12) subjected
      to PP with or without pretreatment with OPC-31260. Rats subjected to PP had
      higher plasma AVP levels than did controls (17.3 +/- 8.1 pg/ml vs 1.5 +/- 0. 6
      pg/ml, P < 0.05). In rats pretreated with vehicle, PP decreased urine output,
      excretion of water, and urea nitrogen, leading to reduced serum osmolality and
      serum sodium levels as well as elevated blood urea nitrogen levels. OPC-31260
      pretreatment improved urine output, excretion of water, and urea nitrogen,
      thereby preventing changes in serum osmolality, serum sodium levels, and blood
      urea nitrogen levels. OPC-31260 pretreatment did not affect GFR. Results suggest
      that plasma AVP contributes to the oliguria due to PP. OPC-31260 may be useful in
      treating the water retention associated with PP.

PMID- 9758725
TI  - Lymphokine-activated killer (LAK) cell anti-HIV-1 ADCC reactivity: a potential
      strategy for reduction of virus-infected cellular reservoirs.
AB  - Lymphocytes from HIV-1-seropositive and -seronegative individuals were examined
      to determine whether HIV-1 infection interfered with the ability to generate a
      lymphokine-activated killer (LAK) cell response. Following a 3-day ex vivo
      incubation in the presence of 1000 U/ml of recombinant interleukin-2, lymphocytes
      from seropositive individuals exhibited a LAK cell response which was equivalent
      to or greater than that of seronegative controls as measured against Daudi cell
      targets. LAK cells from seropositive and seronegative donors showed no specific
      cytolytic activity against gp120-coated or HIV-1-infected targets. However, in
      the presence of patient sera, significant levels of virus-specific LAK cell
      mediated antibody-dependent cellular cytotoxicity (ADCC) were observed. The level
      of this specific LAK cell-mediated ADCC was greater than that mediated under
      similar conditions by freshly isolated peripheral blood mononuclear cells. The
      greatest improvement in ADCC over baseline activity was seen with lymphocytes
      from AIDS patients after the 3-day ex vivo activation, suggesting that this
      patient population might benefit the most from adaptive LAK cell therapy.

PMID- 9758726
TI  - Nitric oxide causes apoptosis in pulmonary vascular smooth muscle cells.
AB  - Nitric oxide (NO), a product of certain cytokine-activated cells, affects rates
      of apoptosis, a mechanism of programmed cell death. We asked whether NO affected
      rates of apoptosis in pulmonary vascular cells. Using rat pulmonary artery smooth
      muscle cells, we studied direct effects of the NO donor SG-nitroso-acetyl-D,L
      penicillamine (SNAP) and the effects of NO endogenously synthesized in response
      to bacterial lipopolysaccharide (LPS) and inflammatory cytokines interleukin
      1beta, interferon-gamma, and tumor necrosis factor-alpha (a combination called
      cytomix for convenience). We determined apoptosis on the basis of light
      microscopy and the bromodeoxyuridine terminal deoxynucleotidyl transferase
      reaction (BrdUTdT). Both SNAP- and cytomix-induced synthesis of NO resulted in
      histologic evidence of apoptosis based upon fluorescence microscopy using
      propidium iodide. SNAP (10(-5) M) increased BrdUTdT-positive cells from 17.5 to
      78.4% compared with basal medium alone, with the maximal response occurring at 15
      h or exposure. Exposing cells to LPS and cytokines induced NO production (from
      0.1 +/- 0.1 to 24.6 +/- 0.5 microM, P < 0.05) caused cytological changes
      consistent with apoptosis and led to an increase of increased BrdUTdT-positive
      cells from 11 to 41% at 12 h compared with basal medium alone. The competitive NO
      synthase inhibitor NG-monomethyl-L-arginine inhibited both NO synthesis and NO
      apoptosis, returning the proportion of BrdUTdT-positive cells (6%) to levels
      below control. L-Arginine (0.5 mM) restored percentages to those increase in
      response to endogenously synthesized NO, and NO is a potential mechanism of acute
      lung injury in response to inflammatory cytokines.

PMID- 9758727
TI  - IL-10 and GM-CSF expression and the presence of antigen-presenting cells in
      chronic venous ulcers.
AB  - BACKGROUND: White cell trapping and activation occurs in the legs of patients
      having chronic venous insufficiency (CVI), and it is thought that this process
      may be important in the development of CVI ulcers. This study has compared the
      tissue distribution of proinflammatory (GM-CSF) and anti-inflammatory cytokines
      (IL-10) and inflammatory cell markers (CD68, HLA-DR) between CVI ulcers, other
      chronic and acute wounds, and autologous nonwounded skin to determine whether
      cell-mediated immunity (CMI) is impaired in CVI ulcers. METHODS: Wound and donor
      site tissue was obtained from 10 patients with CVI ulcers and 10 patients with
      other chronic and acute wounds. Serial Formalin-fixed sections were processed by
      standard hematoxylin and eosin staining or by indirect immunoperoxidase
      histochemical staining. RESULTS: HLA-DR-positive antigen-presenting cells (APC),
      including CD68-positive macrophages and dermal dendritic cells, were found with
      greater frequency in CVI ulcers than in other chronic or acute wounds (P =
      0.0015) or in the autologous CVI donor site tissue (P = 0.006). CVI ulcers also
      demonstrated increased IL-10 staining of the entire epidermis compared to non-CVI
      wounds (P = 0.0019) or autologous donor site tissue (P = 0.004), whereas there
      was no significant change in the presence of the counteracting cytokine, GM-CSF.
      CONCLUSIONS: These findings suggest that although the cellular components of CMI
      are present in CVI ulcers, their function may be impaired by the increased level
      of IL-10. Future studies will examine whether IL-10-mediated suppression of CMI
      and/or inhibition of GM-CSF-stimulated keratinocyte proliferation may contribute
      to the chronic nature of CVI ulcers.

PMID- 9758728
TI  - The Kidney's role in glucose balance following partial hepatectomy.
AB  - It has long been believed that the liver is the major contributor to glucose
      balance during fasting and stressful situations. Recently, investigators have
      implicated the kidney as having a significant contribution to systemic glucose
      appearance. We studied the relative contributions of the kidney and liver to
      glucose homeostasis in fasted nonoperated, sham-operated, and 70% hepatectomized
      rats. Systemic glucose appearance, renal glucose release and uptake, and hepatic
      glucose release were determined by glucose balance and isotopic dilution
      techniques. Systemic glucose appearance remained unchanged following hepatectomy.
      There was a significant output of glucose by the kidney in all groups, accounting
      for >50% of total glucose appearance. Despite the kidney's appreciable
      contribution to circulating glucose in the postabsorptive state, renal glucose
      release was not increased in the hepatectomized rats compared to controls. Total
      glucose appearance was maintained following hepatectomy by an increase in hepatic
      glucogenesis. There was a significant increase in the rate of hepatic glucose
      release from resected rats when normalized to gram of remaining liver (P <
      0.001). Despite the substantial amount of renal glucose output in the
      postabsorptive state, preservation of glucose balance following 70% hepatectomy
      is accomplished by adaptation in hepatic glucose output.

PMID- 9758729
TI  - Acute administration of liposomal coenzyme Q10 increases myocardial tissue levels
      and improves tolerance to ischemia reperfusion injury.
AB  - The antioxidant and bioenergetic effects of CoQ10 (CoQ) suggest it might be ideal
      therapy for acute myocardial ischemia. Its utility is limited by the requirement
      for enteral administration. This study related the administration of a new
      liposomal suspension of CoQ given intravenously to (1) serum and myocardial [CoQ]
      and (2) recovery of function, myocardial efficiency, and oxidant injury after
      cardiac ischemia and reperfusion (I/R). Rats (n = 8/group) were given liposomal
      CoQ 10 mg/kg iv or placebo (Control), 15 min (C-15), 30 min (C-30), and 60 min (C
      60) before (1) measurement of serum and myocardial CoQ or (2) Langendorff
      perfusion of hearts subjected to 15 min equilibration, 25 min ischemia (37
      degrees C), and 40 min reperfusion (RP). Developed pressure (DP) was measured via
      an intraventricular balloon and coronary flow was measured by a digital flow
      meter. Myocardial efficiency was defined as DP/MVO2 where MVO2 = microl O2
      consumed/min/gram LV. At end RP hearts were assayed for CK, an oxidant sensitive
      enzyme. Maximum preischemic CoQ levels in serum and myocardium occurred 15 and 30
      min after administration, respectively. At end reperfusion, C-30 hearts improved
      the most, recovering 75 +/- 4% of their preischemic DP while Control recovered
      only 52 +/- 6% (P < 0.03) as well as maintaining better myocardial efficiency
      (0.69 +/- 0.02 vs Control, 0.43 +/- 0.05) (P < 0.001). C-15, C-30, and C-60
      groups all lost less CK activity after RP vs Control (P < 0.04). CONCLUSION: (1)
      Serum and myocardial levels of CoQ can be raised acutely by iv liposomal CoQ. (2)
      Myocardial CoQ levels correlate best with I/R protection. (3) Acute iv CoQ
      improves function and efficiency and decreases oxidant injury after I/R.
      Intravenous CoQ may be effective clinically for acute cardiac ischemic syndromes.

PMID- 9758730
TI  - Application of a rat osteomyelitis model to compare in vivo and in vitro the
      antibiotic efficacy against bacteria with high capacity to form biofilms.
AB  - A rat experimental osteomyelitis model was used to study the efficiency of
      antibiotics on biofilm bacteria adhered to implants in relation to the efficiency
      obtained in vitro. In the osteomyelitis model, 10(4) bacteria of the strain
      variant used for the in vitro studies (a slime-producing variant of
      Staphylococcus aureus) were inoculated into the rat tibia at surgery, after
      implanting a stainless steel canula precolonized for 12 h with this strain. After
      5 weeks, a 21-day antibiotic treatment was applied (using cefuroxime, vancomycin,
      or tobramycin). Subsequently, implant and tibia were studied for presence of
      bacteria. In this osteomyelitis model, cefuroxime inhibited bone colonization and
      reduced the number of bacteria in metal and bone at a higher degree (P < 0.05)
      than vancomycin and trobramycin (the latter antibiotic did not have this
      reduction effect). The in vitro assay was applied using three concentrations of
      each antibiotic (8, 100, and 500 microg/ml) and 6-, 24-, and 48-h biofilms.
      Bacterial viability was evaluated by ATP-bioluminescence after 24 h of antibiotic
      treatment. In this in vitro assay, cefuroxime significantly (P < 0.05) reduced in
      all cases the number of viable bacteria in biofilms, tobramycin did not affect
      viability, and vancomycin affected viability except at the lowest concentration
      used (8 microg/ml, i.e., 8x the minimal bactericidal concentration of this
      antibiotic) when facing the oldest (48 h) biofilm. These results demonstrate the
      usefulness of the osteomyelitis model applied in providing evidence for a close
      correlation between the in vitro and in vivo findings on the effect of three
      antibiotics under study.

PMID- 9758731
TI  - Oral dehydroepiandrosterone inhibits the growth of human pancreatic cancer in
      nude mice.
AB  - BACKGROUND: Dehydroepiandrosterone (DHEA), an androgen precursor, inhibits the
      induction of pancreatic cancer in some animal models. Our laboratory has
      previously demonstrated that the sulfated form of DHEA (DHAS), when administered
      by intraperitoneal injection, inhibits the growth of pancreatic cancer xenografts
      in nude mice. In the present study, we hypothesize that DHEA-mediated pancreatic
      cancer growth inhibition is associated with alterations in plasma sex hormone
      concentrations. MATERIALS AND METHODS: Forty male, nude, athymic mice were fed
      either Teklad 22/5 rodent diet or diet supplemented with 0.6% DHEA ad libitum.
      Four weeks following the institution of the experimental diets, 1 x 10(6) MiaPaCa
      2 cells were injected into the right flank of each animal. Tumor area was
      recorded weekly and tumor weights were measured after 5 weeks. Plasma DHAS,
      testosterone, and progesterone concentrations were determined by
      radioimmunoassay. RESULTS: Plasma DHAS, testosterone, and progesterone
      concentrations were all significantly elevated in the DHEA-treated group. DHEA
      treated mouse plasma DHAS concentrations were approximately 50-fold higher than
      controls. Mean tumor weight was significantly reduced in the DHEA group (68.9 +/-
      39.1 vs 121.0 +/- 64.3). DHEA treatment did not result in significant animal
      weight reductions and toxic side effects were not observed. CONCLUSIONS: Dietary
      supplementation with 0.6% DHEA causes significant elevations in plasma DHAS
      concentration. DHEA administration significantly inhibits pancreatic cancer cell
      growth at plasma concentrations 1 x 10(5)-fold lower than previously reported.
      The mechanism of action may involve elevated concentrations of sex hormones.

PMID- 9758732
TI  - Glucocorticoid attenuates a decrease of antithrombin III following major surgery.
AB  - BACKGROUND: Major surgery, such as esophagectomy, activates inflammatory
      responses and the coagulation system, and this activation is characterized by
      release of inflammatory cytokines and a decrease in antithrombin-III (AT-III),
      respectively. Preoperative glucocorticoid administration has been reported to
      suppress circulatory cytokine levels after major surgery. PATIENTS AND METHODS: A
      total of 28 patients underwent esophagectomy for esophageal carcinoma; 14 of them
      were given 10 mg/kg of methylprednisolone intravenously upon induction of
      anesthesia and 14 served as controls. Circulating levels of tumor necrosis factor
      alpha (TNF-alpha), interleukin 6 (IL-6), polymorphonuclear (PMN) elastase,
      thrombin-antithrombin III complex (TAT), AT-III, and albumin were measured before
      and immediately after the operation and on postoperative days (PODs) 1, 3, 5, and
      7. RESULTS: TNF-alpha, IL-6, and TAT levels significantly increased after
      esophagectomy in both groups. AT-III and albumin decreased to their minimum
      levels on POD 1 and POD 3, respectively. Methylprednisolone treatment effectively
      inhibited the increases in TNF-alpha and IL-6 and the decreases in AT-III and
      albumin, but did not inhibit the increases in PMN-elastase and TAT levels. There
      were significant correlations between AT-III, IL-6, and albumin levels.
      CONCLUSIONS: These results suggest that methylprednisolone pretreatment
      attenuates the decrease in AT-III by reducing IL-6 production postoperatively.

PMID- 9758733
TI  - Pyruvate augments mechanical function via activation of the pyruvate
      dehydrogenase complex in reperfused ischemic immature rabbit hearts.
AB  - BACKGROUND: Reperfusion of ischemic adult hearts is associated with increased
      fatty acid oxidation, reduced pyruvate oxidation, and reduced pyruvate
      dehydrogenase (PDH) activity, leading to a decrease in cardiac efficiency. These
      effects may be amplified in newborn hearts because of the immaturity of their PDH
      pathway. We hypothesize that pyruvate can augment mechanical function in the
      immature heart by activating the PDH complex (PDC) during reperfusion in severely
      ischemic hearts. MATERIALS AND METHODS: Seven-day old isolated working rabbit
      hearts (n = 12) were perfused with modified Krebs solution containing 0.4 mM
      palmitate. Pyruvate (5 mM) was added for a 10-min period either before or after a
      30-min period of normothermic global ischemia. Cardiac functional indices before
      global ischemia and during reperfusion were correlated with active and total PDC
      activity measured in 28 additional hearts frozen at the various time points
      throughout the perfusion protocol. RESULTS: Addition of pyruvate before ischemia
      increased the proportion of active PDC but did not affect any measured functional
      indices. During early reperfusion, aortic flow, cardiac output, and cardiac work
      were all significantly depressed compared to preischemic values. Addition of
      pyruvate significantly increased the proportion of active PDC and was also
      associated with a significant increase in aortic flow, cardiac work, and
      developed pressure. Removal of pyruvate from the perfusate resulted in a
      subsequent significant decrease in PDC activity and these functional parameters.
      CONCLUSION: During reperfusion of neonatal rabbit hearts, addition of pyruvate
      improves cardiac performance in association with activation of PDC.

PMID- 9758734
TI  - In vitro effects of Clostridium difficile toxins on hepatocytes.
AB  - BACKGROUND: Clostridium difficile infections are associated with development of
      the systemic inflammatory response, including the production of hepatic acute
      phase proteins. Lipopolysaccharide (LPS) directly stimulates the production of at
      least one of these proteins, a 23-kDa acute phase protein (the LPS-induced
      protein, or LIP) by murine hepatocytes in vitro. The aim of the present study was
      to determine if C. difficile toxins also stimulated the synthesis of this protein
      in vitro. METHODS: Cultured murine hepatocytes were treated for 24 h with various
      concentrations of C. difficile culture extract or purified toxins A and B in the
      presence or absence of dexamethasone or interleukin-1 (IL-1) receptor antagonist
      (IL-1 RA). The cells were then metabolically radiolabeled with [35S]methionine.
      Secretory proteins were identified using electrophoresis and autoradiography, and
      their synthesis was quantitated by image analysis of the autoradiograms. RESULTS:
      The C. difficile culture extract, at dilutions as low as 1:200,000, significantly
      stimulated LIP synthesis in vitro. Toxins A and B, at concentrations as low as
      1.6 and 0.02 pg/ml, respectively, also induced production of this protein.
      Dexamethasone further augmented C. difficile toxin-stimulated synthesis of LIP,
      but IL-1 RA inhibited the effects of these toxins on the synthesis of this
      protein. Only minimal quantities of IL-1 were found in culture supernatants
      following treatment with the toxins. CONCLUSIONS: C. difficile toxins A and B, at
      very low concentrations, stimulate hepatocyte acute phase protein synthesis. Even
      though IL-1 RA inhibits this process, it does not appear that local production of
      IL-1 mediates the action of these toxins.

PMID- 9758736
TI  - Association for academic surgery, 32nd annual meeting 

PMID- 9758735
TI  - Interleukin 10 inhibits alveolar macrophage production of inflammatory mediators
      involved in adult respiratory distress syndrome.
AB  - BACKGROUND: Adult respiratory distress syndrome (ARDS) causes severe morbidity
      and mortality in trauma patients. One potential method to attenuate the lung
      injury is to inhibit alveolar macrophage production of proinflammatory mediators.
      The purpose of this study was to investigate the cellular mechanism of
      interleukin 10 (IL-10) inhibition on LPS-stimulated macrophage (Mphi). We
      hypothesized that IL-10 inhibited phospholipase C signal pathways in Mphi. IL-10
      inhibition would be restored by calcium ionophores and protein kinase C (PKC)
      activation. METHODS: Rabbit alveolar Mphi were obtained by bronchoalveolar
      lavage. Mphi were treated with Escherichia coli LPS (10 ng/ml) in the presence of
      various concentrations of human IL-10. Cell lysates and supernatant were analyzed
      for proagulants (PCA) and tumor necrosis factor (TNF), respectively. TNF mRNA
      expression of alveolar Mphi was also measured by Northern Blot assay. Macrophage
      PGE2 production was measured by ELISA. RESULTS: IL-10 inhibited the production of
      both TNF and PCA by LPS-stimulated Mphi. In addition, IL-10 also reduced TNF mRNA
      expression. Similarly, PGE2 production by LPS-stimulated Mphi was also attenuated
      by IL-10. An increase in the intracellular [Ca2+] induced by A23187 failed to
      reverse this IL-10-mediated inhibition. In comparison, phorbol myristate acetate,
      a protein kinase C (PKC) activator, restored TNF and PCA production despite the
      presence of IL-10. CONCLUSIONS: IL-10 inhibits Mphi production of inflammatory
      mediators. This inhibition is, at least in part, mediated by modulating the PKC
      activity.

PMID- 9758737
TI  - Identification of EEG events in the MR scanner: the problem of pulse artifact and
      a method for its subtraction.
AB  - Triggering functional MRI (fMRI) image acquisition immediately after an EEG event
      can provide information on the location of the event generator. However, EEG
      artifact associated with pulsatile blood flow in a subject inside the scanner may
      obscure EEG events. This pulse artifact (PA) has been widely recognized as a
      significant problem, although its characteristics are unpredictable. We have
      investigated the amplitude, distribution on the scalp, and frequency of
      occurrence of this artifact. This showed large interindividual variations in
      amplitude, although PA is normally largest in the frontal region. In five of six
      subjects, PA was greater than 50 microV in at least one of the temporal,
      parasagittal, and central channels analyzed. Therefore, we developed and
      validated a method for removing PA. This subtracts an averaged PA waveform
      calculated for each electrode during the previous 10 s. Particular attention has
      been given to reliable ECG peak detection and ensuring that the average PA
      waveform is free of other EEG artifacts. Comparison of frequency spectra for EEG
      recorded outside and inside the scanner, with and without PA subtraction, showed
      a clear reduction in artifact after PA subtraction for all four frequency ranges
      analyzed. As further validation, lateralized epileptiform spikes were added to
      recordings from inside and outside the scanner: PA subtraction significantly
      increased the proportion of these spikes that were correctly identified and
      decreased the number of false spike detections. We conclude that in some
      subjects, EEG/fMRI studies will be feasible only using PA subtraction.

PMID- 9758738
TI  - Phase navigator correction in 3D fMRI improves detection of brain activation:
      quantitative assessment with a graded motor activation procedure.
AB  - Motion poses severe problems for BOLD fMRI, particularly in clinical studies, as
      patients exhibit more involuntary movements than controls. This study focuses on
      the merits of a motion correction technique incorporated in multishot fMRI scans,
      so-called phase navigator correction. The technique entails real-time assessment
      and off-line elimination of signal fluctuations caused by subject motion. The
      purpose of this study was to quantify and characterize the effect of this type of
      improvement on 3D fMRI brain activity maps. For imaging, the 3D PRESTO method was
      used, with a relatively simple finger opposition task. The followed strategy was
      guided by the notion that application of any fMRI imaging tool in clinical
      studies requires several qualities, such as high and spatially homogeneous
      sensitivity to brain activity, and low sensitivity to motion. A graded motor
      activation protocol in 10 healthy subjects revealed that image stability was
      improved by approximately 20%, by the use of phase navigator correction. As a
      result, sensitivity for task-related BOLD signal change was enhanced considerably
      in the brain activity maps. Implications for use of this fMRI technique in
      patient studies are discussed.

PMID- 9758739
TI  - Reproducibility of fMRI results across four institutions using a spatial working
      memory task.
AB  - Four U.S. sites formed a consortium to conduct a multisite study of fMRI methods.
      The primary purpose of this consortium was to examine the reliability and
      reproducibility of fMRI results. FMRI data were collected on healthy adults
      during performance of a spatial working memory task at four different
      institutions. Two sets of data from each institution were made available. First,
      data from two subjects were made available from each site and were processed and
      analyzed as a pooled data set. Second, statistical maps from five to eight
      subjects per site were made available. These images were aligned in stereotactic
      space and common regions of activation were examined to address the
      reproducibility of fMRI results when both image acquisition and analysis vary as
      a function of site. Our grouped and individual data analyses showed reliable
      patterns of activation in dorsolateral prefrontal cortex and posterior parietal
      cortex during performance of the working memory task across all four sites. This
      multisite study, the first of its kind using fMRI data, demonstrates highly
      consistent findings across sites.

PMID- 9758741
TI  - Human prefrontal cortex is not specific for working memory: a functional MRI
      study.
AB  - Lesion studies in monkeys have provided evidence that lateral prefrontal cortex
      is necessary for working memory, the cognitive processes involved in the
      temporary maintenance and manipulation of information. Monkey
      electrophysiological studies, however, have also observed prefrontal neuronal
      activity associated with cognitive processes that are nonmnemonic. We tested the
      hypothesis that the same regions of human prefrontal cortex that demonstrate
      activity during working memory tasks would also demonstrate activity during tasks
      without working memory demands. During echoplanar fMRI imaging, subjects
      performed a three-condition experiment (working memory task, nonworking memory
      task, rest). In the working memory task, subjects observed serially presented
      stimuli and determined if each stimulus was the same as that presented two
      stimuli back. The nonworking memory task in Experiment 1 required subjects to
      identify a single predetermined stimulus; in Experiment 2, subjects were required
      to make a button press to every stimulus. In all subjects in both experiments,
      the working memory task exhibited greater prefrontal cortical activity compared
      to either nonworking memory task. In these same prefrontal regions, greater
      activation was also observed during both nonworking memory tasks compared to
      rest. We conclude that human lateral prefrontal cortex supports processes in
      addition to working memory. Thus, reverse inference of the form "if prefrontal
      cortex is active, working memory is engaged" is not supported.

PMID- 9758740
TI  - Neural correlates of memory retrieval during recognition memory and cued recall.
AB  - Regional brain activity, measured by H215O PET, was investigated during
      recognition memory and word-stem cued recall of words in order to compare the
      neural correlates of two components of memory retrieval-effort and success-as a
      function of task. For each task there was a baseline and two retrieval
      conditions. In one retrieval condition (zero density), none of the test items
      corresponded to words encoded in a preceding study phase. Differences in activity
      between this condition and the baseline were employed to characterize the neural
      correlates of retrieval effort in each task. In the other retrieval condition
      (high density), 80% of the test items had been studied previously. Differences in
      brain activity between this condition and the zero-density condition were taken
      to represent the neural correlates of successful retrieval. The principal
      findings concern the right anterior prefrontal cortex, a region demonstrated
      previously to be active during episodic retrieval. Relative to baseline, this
      region showed no evidence of activation in the zero-density condition of the
      recognition task, but did show enhanced activity in the equivalent condition of
      the cued-recall task. In contrast, relative to the zero-density condition, the
      high-density condition was associated with increased right prefrontal activity
      during recognition, but reduced activity during cued recall. It is proposed that
      the right prefrontal cortex supports cognitive processes that operate on
      information retrieved in response to a test item and that these processes
      contribute to the evaluation of whether the information represents an appropriate
      prior episode.

PMID- 9758742
TI  - Influence of ANOVA design and anatomical standardization on statistical mapping
      for PET activation.
AB  - We have created images of z value, error, and variation components for a PET
      activation study using various ANOVA designs and anatomical standardization
      methods. Data were acquired in four PET centers. In each center, CBF was measured
      on six normal male subjects under resting and covert verb generation, three times
      for each. The images were anatomically standardized with LINEAR transformation,
      SPM (Ver. 95), HBA (Karolinska/Tohoku), or MICHIGAN (Minoshima). ANOVA was
      performed pixel by pixel to compute t (and z) for the task main effect (Verb vs
      Rest) in four different designs: (i) two way (subject and task) (2W), (ii) two
      way with interaction (2WI), (iii) subject considered a random factor (2WI-MX),
      and (iv) three-way (subject, task, and replication) (3W). A large area extending
      from the Broca to the left premotor cortex was activated. The localization of the
      highest peak depended both on the anatomical standardization and on the ANOVA
      design, the variation ranging 3-4 cm. Smoothing reduced the variation while
      erasing possible subfoci. The z images of 2W, 2WI, and 3W looked alike, whereas
      2WI-MX presented lower peak z values. SPM tended to present higher z values than
      the other methods. The error was high in the gray and low in the white matter.
      The root mean square for the subject effect was high on the border of gray matter
      especially in LINEAR and HBA, revealing intersubject mismatch in the gray matter
      distribution. The root mean square for the subject-by-task interaction effect
      revealed individual variation in activation.

PMID- 9758743
TI  - The inferential impact of global signal covariates in functional neuroimaging
      analyses.

PMID- 9758744
TI  - High-level expression of branching enzyme II from maize endosperm in Escherichia
      coli.
AB  - The gene that encodes the mature branching enzyme II (BEII) protein from maize
      (Zea mays L.) endosperm was amplified by means of a polymerase chain reaction
      technique and inserted into a T7-based expression vector. Although this has been
      an efficient expression system of maize BEII in Escherichia coli, an example is
      presented in this report which allows a greater expression of mBEII protein from
      the bacterial system by changing only one codon. The key to the level of
      expression appears to be related to the conversion of the third thymine base in
      the 285 position codon of the mBEII cDNA to cytosine without altering the encoded
      mBEII protein product. The crude cell extracts of enzyme prepared from E.coli
      exhibited seven-fold higher expression of branching enzyme activity compared to
      expression of the native enzyme. The enzymes from wild-type and the silent
      mutation genes were purified. The proteins were indistinguishable kinetically and
      immunologically. Thus, we obtained a significantly improved expression of mBEII
      protein in the bacterial system.

PMID- 9758745
TI  - Effect of promoters and signal sequences on the production of secreted HIV-1
      gp120 protein in the baculovirus system.
AB  - We compared insect cell production levels of secreted HIV-1 gp120 glycoprotein
      encoded by five different baculovirus expression constructs. Combinations
      consisting of one of two baculovirus promoters (very late or hybrid late/very
      late) and one of three different signal sequences [human tissue plasminogen
      activator (tpa), human placental alkaline phosphatase (pap), or baculovirus
      envelope glycoprotein (gp67)] were constructed. Production of secreted gp120 from
      these constructs was analyzed in two enzyme-linked immunosorbent assay formats,
      one detecting the total amount of secreted gp120 protein and the other measuring
      the level of "active" gp120 (as defined by the ability to bind to CD4). We found
      that for all of the constructs, approximately 50 to 90% of the secreted gp120
      protein was active. Furthermore, our results indicated that expression from
      either promoter yielded comparable production of secreted protein, despite the
      fact that transcription from the hybrid promoter begins at an earlier time. By
      contrast, the signal sequence had a much greater effect on the levels of secreted
      gp120: the tpa leader yielded the highest level of secreted protein, followed by
      the gp67 and pap sequences. This result suggests that transcription is not a
      limiting factor in the production of secreted gp120, but rather that downstream
      processing of the protein is more critical. Furthermore, these results confirm
      the notion that the "optimal" signal sequence is protein dependent and that an
      insect-derived signal sequence is not optimal in all cases.

PMID- 9758746
TI  - TolAIII co-overexpression facilitates the recovery of periplasmic recombinant
      proteins into the growth medium of Escherichia coli.
AB  - Overproduction of the third topological domain of the transmembrane protein TolA
      (TolAIII) in the periplasm of Escherichia coli confers a "leaky" phenotype to
      host cells by disrupting the integrity of the outer membrane and causing
      periplasmic proteins to leach into the growth medium. To examine the
      physiological consequences of TolAIII overexpression in more detail and assess
      the usefulness of this strategy for the release of periplasmic recombinant
      proteins into the extracellular fluid, we constructed a ColE1-compatible plasmid
      encoding a fusion between the ribose binding protein signal sequence and TolAIII
      under T7lac transcriptional control. About half of the total TolAIII synthesized
      in IPTG-induced cells aggregated in a precursor form in the cytoplasm. However,
      the majority of the mature protein was soluble and located in the extracellular
      fluid. TolAIII-overproducing cultures exhibited only slight growth defects upon
      entry into stationary phase but underwent extensive lysis when treated with 0.1%
      (w/v) SDS, and were unable to divide when supplemented with 0.02% SDS. The loss
      of outer membrane integrity resulted in long-term damage since cell viability was
      reduced by three orders of magnitude compared to control or uninduced cells.
      Overexpression of TolAIII did not significantly interfere with the translocation
      and processing of a plasmid-encoded fusion between the OmpA signal sequence and
      TEM-beta-lactamase but led to the release of most periplasmic proteins and 90% of
      the active enzyme into the extracellular fluid. Although the total levels of beta
      lactamase accumulation in TolAIII-overproducing cultures was only 1.5- to 2-fold
      less than in control cells, the formation of periplasmic inclusions bodies was
      completely suppressed. A threshold concentration of TolAIII was necessary for
      efficient release of periplasmic proteins since the viability and detergent
      sensitivity of uninduced cells was comparable to that of control cultures and 80%
      of the beta-lactamase synthesized remained confined to the periplasm.

PMID- 9758747
TI  - Purification and interfacial behavior of recombinant human gastric lipase
      produced from insect cells in a bioreactor.
AB  - Recombinant human gastric lipase (rHGL) (EC 3.1.1.3) was produced on a large
      scale (5-13 mg/liter) from recombinant baculovirus-infected insect cells using a
      bioreactor apparatus. Here an improved procedure is described for purifying rHGL
      involving the use of cation exchange chromatography followed by immunoaffinity
      column methods, which gives a total yield of 62% and a purification factor of
      464, using 10% isopropanol in all the purification buffers. The presence of
      isopropanol was necessary to preserve the stability of the enzyme during the
      chromatographic separation steps. The specific activity of rHGL on
      tributyroylglycerol (700 U/mg) was lower than that of native HGL (nHGL) (1080
      U/mg). The rHGL interfacial adsorption kinetics were studied by recording the
      changes in the surface pressure with time in the presence or absence of an egg
      phosphatidycholine monomolecular film spread at the air/water interface at
      various initial surface pressures. The surface behavior of rHGL was similar to
      that of nHGL. It can be concluded that the lipid binding affinity of rHGL is
      identical to that of the native lipase and, consequently, that the presence of
      detergents and lipids in the insect cell culture media did not affect the
      interfacial behavior of the purified rHGL. It will be therefore possible to
      specifically study the binding step of HGL mutants to a lipid monolayer.

PMID- 9758748
TI  - Recombinant human retinol-binding protein refolding, native disulfide formation,
      and characterization.
AB  - Human retinol-binding protein (RBP) is a monomeric 21-kDa protein that is
      currently the subject of numerous studies owing to its role in the cellular
      uptake and utilization of retinol. When the RBP gene is overexpressed in
      Escherichia coli, inclusion bodies of aggregated RBP are found in the cells.
      These inclusion bodies are solubilized in 5.0 M GdmCl containing 10 mM DTT.
      Refolding of RBP is carried out in the presence of vitamin A by diluting
      denatured and reduced RBP into a redox refolding buffer consisting of 3 mM
      cysteine/0.3 mM cystine at 4 degreesC. Ion exchange chromatography (HPLC) is
      utilized to purify refolded RBP to homogeneity as demonstrated by SDS-PAGE and
      electrospray MS. The native structure of refolded RBP was established by its
      ability to bind to vitamin A and the plasma protein transthyretin. The
      reconstitution of RBP outlined within affords a 50-60% overall yield, i.e., 73 mg
      of pure RBP/L of E. coli culture.

PMID- 9758749
TI  - Production of recombinant human monocyte/neutrophil elastase inhibitor (rM/NEI).
AB  - Recombinant human monocyte/neutrophil elastase inhibitor (rM/NEI) was expressed
      with a baculovirus expression system. The purified recombinant protein was shown
      to inhibit human neutrophil elastase by the formation of a stable equimolar
      complex, as had been shown for M/NEI isolated from monocyte-derived cell lines.
      rM/NEI was remarkably stable in aqueous buffers from pH 6 to pH 8, but not in
      buffers below pH 6. rM/NEI activity was stable when subjected to freeze-thaw
      cycles and low temperature storage in Tris or phosphate buffers. rM/NEI could
      also be lyophilized without significant loss of activity. A 1.6-g batch of
      greater than 95% purity in rM/NEI was obtained by anion exchange and size
      exclusion chromatography with yields of 7 to 8 mg per liter of cultured insect
      cells. Methods and protocols were chosen for compatibility with large-scale cGMP
      production and were suitable for biochemical characterization and preclinical
      evaluation of rM/NEI as a therapeutic agent for cystic fibrosis. The availability
      of large amounts of purified rM/NEI will facilitate clinical evaluation of rM/NEI
      for prevention of the elastase-mediated destruction of lung tissue associated
      with the morbidity and mortality of cystic fibrosis.

PMID- 9758750
TI  - Coexpression of G-CSF with an unglycosylated G-CSF receptor mutant results in
      secretion of a stable complex.
AB  - Previously, we have shown that the entire extracellular domain of the granulocyte
      colony stimulating factor receptor (sG-CSFr) produced in Chinese hamster ovary
      (CHO) cells forms a stable complex with its ligand G-CSF, at a stoichiometry of
      2:2. A truncated receptor molecule consisting of the cytokine receptor homology
      domain and N-terminus Ig-like domain (Ig CRH) behaves quite similarly. Both of
      these forms of the receptor are highly glycosylated. To address the importance of
      glycosylation toward receptor activity and stability, and possibly obtain
      nonglycosylated receptor for crystallization, mutations were made to replace four
      Asn residues which are N-glycosylated in the truncated receptor. Virtually no
      receptor was recovered from conditioned media of CHO cells transfected with this
      mutant construct, although a high-level of mRNA coding for receptor was detected;
      this mRNA was translated as determined by Western blots of cell lysates. These
      results indicate that the translated product is apparently not secreted from
      these cells. Cells transfected with mutant receptor cDNA were cotransfected with
      a cDNA construct expressing G-CSF in which the single O-glycosylation site was
      eliminated by mutation. Upon fermentation of the cotransfectants, we observed a
      large amount of receptor-ligand complex in the conditioned media. The purified
      unglycosylated complex appeared to be of the same binding stoichiometry and
      approximate binding affinity as that of complex formed by addition of purified
      ligand and unmutated receptor. These results show that while glycosylation of sG
      CSFr is not necessary for ligand binding, it appears to be crucial in folding and
      export from the cell.

PMID- 9758751
TI  - Expression and purification of HIV-I p15NC protein in Escherichia coli.
AB  - An efficient method for the expression and purification of nucleocapsid precursor
      protein (p15NC) from HIV-I (BH 10 isolate) was developed and used to obtain large
      quantities of this viral protein for structural studies, protein biochemistry,
      and high-throughput screening efforts. We have engineered an existing p15NC clone
      into a new vector developed at the University of Heidelberg, Germany. Using PCR,
      we introduced new restriction sites and a strong ribosome-binding site in the
      p15NC gene and expressed authentic p15NC protein. Our protocol enabled us to
      rapidly obtain soluble and highly stable p15NC expressed in Escherichia coli and
      to purify several milligrams of p15NC to homogeneity. In the current purification
      scheme, lysis of cell paste followed by a simple three-step FPLC procedure yields
      about 0.4-0.5 mg of purified p15NC per gram of E. coli cell paste expressing the
      protein with an overall yield of 45%. The purified p15NC retained its ability to
      bind full-length HIV-I p15NC mRNA in solution- or solid-phase-based assays. A
      specific stem-loop forming RNA fragment (24-mer) and its antisense DNA oligomer
      (21-mer) derived from the full-length p15NC mRNA were also able to bind to p15NC.
      In addition, antisense DNA oligos with bulky 5-iodouracil and 5-iodocytidine
      substituents were able to bind to p15NC with little or no perturbations as
      assessed by their ability to compete with the full-length p15NC mRNA in filter
      binding competition assays. In addition, RNA-dependent cleavage of the purified
      p15NC in vitro by HIV-I protease occurred at rates similar to those reported
      previously.

PMID- 9758752
TI  - Purification of elongation factors EF-Tu and EF-G from Escherichia coli by
      covalent chromatography on thiol-sepharose.
AB  - The elongation factors EF-Tu and EF-G of Escherichia coli are involved in the
      transport of aminoacyl-tRNA to ribosomes and the translocation of ribosomes on
      mRNA, respectively. Both possess cysteine residues that are important for
      activity. We took advantage of this property to design a purification protocol
      based on thiol-Sepharose chromatography, a method involving thiol-disulfide
      interchange between protein thiol groups and the glutathione-2-pyridyl-disulfide
      conjugate of the affinity resin. Bacterial cells were lysed by a lysozyme-EDTA
      method, and the lysate supernatant was purified by chromatography on, first, DEAE
      Sephacel and, then thiol-Sepharose. Both elongation factors were purified in a
      single procedure, since DEAE-Sephacel fractions containing both factors were
      loaded on the thiol-Sepharose column. Thiol-Sepharose chromatography efficiently
      separates each elongation factor from all contaminating proteins. The purified
      elongation factors were characterized by SDS-PAGE, protein sequencing, and
      biological activity. The specific reactivities of the elongation factors with
      thiol-Sepharose allow their efficient purification and suggest that they possess
      hitherto undiscovered properties connected with their reactive thiols.

PMID- 9758754
TI  - A nondenaturing purification scheme for the DNA-binding domain of poly(ADP
      ribose) polymerase, a structure-specific DNA-binding protein.
AB  - Poly(ADP-ribose) polymerase (PARP) is thought to be involved in DNA repair given
      its ability to recognize and bind to DNA strand breaks. During apoptosis, PARP is
      proteolytically cleaved into two stable fragments, the N-terminal 25-kDa DNA
      binding domain (DBD) and the 85-kDa fragment containing the automodification and
      catalytic domains. To understand the DNA-binding properties of PARP, we expressed
      a recombinant hexahistidine tagged protein (His-DBD) in Escherichia coli. We
      modified expression to facilitate protein folding by including zinc and reducing
      the induction temperature. Properly folded, the DNA-binding domain of PARP binds
      to single- and double-stranded DNA in a structure-specific manner. To eliminate
      contamination with bacterial DNA that occurred during the purification process, a
      purification procedure was developed to produce DNA-free protein. In addition, to
      remove the hexahistidine tag from the recombinant protein, thrombin cleavage was
      carried out while the recombinant protein was bound to a DNA column. This
      procedure stabilized the recombinant protein and resulted in nearly 100% cleavage
      with no appreciable loss to unwanted proteolytic degradation. This nondenaturing
      purification scheme results in high-quality, native PARP-DBD for use in
      structural and biochemical studies.

PMID- 9758753
TI  - Facile purification of fibrinogen fragments using a computer-based model with
      general applicability to the generation of salt gradients.
AB  - We and others have recently shown that specific fragments of cross-linked fibrin
      affect cell behavior. In order to develop a facile method for the preparative
      scale purification of fibrin fragment D dimer, a simple gradient generating
      system for conventional chromatography was developed and validated, and methods
      of fibrin fragment D dimer purification were compared. The experimentally
      measured salt concentration/time relationship fell directly on the model
      predicted line. Model-predicted changes in the reservoir volume and/or salt
      concentration in the limit buffer affected both the initial slope and the shape
      of the concentration/time relationship. This gradient generation method was used
      to separate the D domains of fibrin(ogen) from the amino terminal region E domain
      using anion-exchange chromatography. While the predicted salt gradient was
      achieved, a salt-dependent separation was found to be less optimal than that of a
      pH-dependent separation, as validated by Coomassie-stained SDS-PAGE and by
      immunoblotting. In conclusion, a facile, user-friendly, computer-based method to
      predict and generate salt gradients was written and validated by direct
      experimentation. While fibrinogen fragment purification was acceptable using this
      system, both separation and yields of fibrinogen and fibrin fragments were
      superior using a pH-based separation technique.

PMID- 9758755
TI  - The chloroplast small heat shock protein--purification and characterization of
      pea recombinant protein.
AB  - We report here on a procedure to obtain large amounts of a chloroplast-localized
      heat shock protein (HSP21) with unknown structure and function, by using an
      Escherichia coli expression system for the pea (Pisum sativum) protein and a
      purification procedure based on perfusion ion-exchange chromatography. After
      initial precipitation steps, the sample was applied to cation- and anion-exchange
      on two columns connected in sequence, which allowed rapid purification of HSP21
      in one equilibration and one elution step. The purified recombinant protein had
      an isoelectric point of 5. 0 and appeared in assembled, oligomeric form
      (approximately 200 kDa) composed of 21-kDa monomers, similar to the native HSP21
      protein as detected by immunoblotting in plants after heat-stress treatment. This
      chloroplast-localized heat shock protein belongs to a special group of small heat
      shock proteins (sHSPs), which share an evolutionary conserved C-terminal domain
      with the vertebrate eye lens alpha-crystallin. The crystallins are known from
      both crystallographic and spectroscopic data to be all-beta proteins. In
      contrast, this paper presents circular dichroism spectroscopy data which shows
      that the purified recombinant HSP21 oligomer has a content of more than 30% alpha
      helical secondary structure.

PMID- 9758756
TI  - Isotopically labeled bovine beta-lactoglobulin for NMR studies expressed in
      Pichia pastoris.
AB  - beta-Lactoglobulin (beta-Lg) is the major whey protein in ruminant milk and has
      been implicated in the irreversible denaturation of milk proteins and its
      associated poor processing behavior during heat treatment. In order to help
      understand this behavior, as well as to facilitate other studies into the
      relationship between the molecular structure and its behavior in solution, we
      have prepared and purified 15N-labeled and 13C/15N-double-labelled beta-Lg in
      sufficient quantities to permit a full determination of the structure and
      dynamics using heteronuclear NMR spectroscopy. The overexpression of the labeled
      protein using the Pichia pastoris system proceeds with good yield but requires
      the removal of significant quantities of copurifying carbohydrate which otherwise
      interfere with the NMR experiments. At pH 2, the resulting material gives triple
      resonance NMR spectra of good quality that are consistent with a monomeric,
      globular protein rich in beta-sheet.

PMID- 9758757
TI  - Expression, purification, and characterization of recombinant ribulose-1,5
      bisphosphate carboxylase/oxygenase large subunit nepsilon-methyltransferase.
AB  - Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) large subunit (LS)
      Nepsilon-methyltransferase (Rubisco LSMT, EC 2.1.1.127) catalyzes methylation of
      the LS of Rubisco. A pea (Pisum sativum L. cv Laxton's Progress No. 9) Rubisco
      LSMT cDNA was expressed in Escherichia coli, but most of the expressed protein
      was found in the insoluble fraction as an inclusion body. Expression at lower
      temperatures increased the level of soluble Rubisco LSMT and the associated
      enzymatic activity. However, the soluble form of Rubisco LSMT occurred as two
      molecular mass forms with the lower molecular mass suggestive of N-terminal
      processing at Ser-37. Deletion of 108 nucleotides from the 5' end encoding the N
      terminal 36 amino acids of Rubisco LSMT resulted in a 10-fold increase in
      solubility and activity. Further addition of a 3' nucleotide sequence coding for
      a hexahistidyl carboxy-terminal peptide enabled purification of the N-terminally
      truncated Rubisco LSMT to homogeneity. Five milligrams of pure recombinant
      Rubisco LSMT was obtained from a 1-liter E. coli cell culture. The apparent
      kinetic constants for recombinant Rubisco LSMT for spinach Rubisco and AdoMet
      were only slightly different from the constants determined using affinity
      purified native Rubisco LSMT from pea chloroplasts. However, there was a 6- to 7
      fold reduction in the kcat for Rubisco LSMT, which was apparently a consequence
      of catalytic inactivation due to exposure to NiSO4 during purification. The
      availability of larger quantities of purified Rubisco LSMT should enable studies
      of the structure-function relationships in Rubisco LSMT and moreover its
      interaction with Rubisco.

PMID- 9758758
TI  - Design of protein purification pathways: application to the proteome of
      Haemophilus influenzae using heparin chromatography.
AB  - The design of efficient protein purification protocols is a scientific challenge
      and can be facilitated by the use of master protein enrichment or purification
      steps. A master purification step is in principle a list including the major
      proteins expected to be present in the various fractions collected from a
      particular enrichment process. Consideration of a master step in the design of a
      purification pathway can reduce the time and effort usually invested in "trial
      and error" approaches. Moreover, master purification steps will certainly become
      valuable tools in the isolation of proteins today designated as hypothetical or
      predicted coding regions, resulting from the sequencing of the various genomes,
      and for which no information on their purification exists. The construction of
      such a master step consists of performance of the protein separation by the
      particular chromatographic method, analysis by two-dimensional polyacrylamide gel
      electrophoresis, and identification by mass spectrometry of the proteins present
      in each fraction. This can be efficiently accomplished now thanks to developments
      in two-dimensional gel technology and large-scale sample throughput mass
      spectrometry. Here we present an example of construction of a master protein
      enrichment step using the soluble protein fraction of the bacterium Haemophilus
      influenzae and applying Heparin chromatography.

PMID- 9758759
TI  - Expression and ligand binding assays of soluble cytokine receptor-immunoglobulin
      fusion proteins.
AB  - We have developed a cloning vector for the expression of type I cytokine
      receptor, NO, extracellular domain (ECD)-mouse IgG1 Fc fusion proteins. The
      vector has a versatile polylinker that allows in-frame cloning of the receptor
      ECD with the mouse IgG1 sequence to encode a receptor ECD-IgG1 fusion construct.
      The receptor-IgG1 fusion proteins are transiently expressed in useful amounts
      following transfection of the expression vector into COS7 cells and G418
      selection. The mouse IgG1 portion of the fusion protein provides a universal
      handle for purification on an affinity matrix and detection by anti-mouse IgG
      antibodies in ELISA or Western blot formats. The expressed receptor ECD-IgG1
      fusion proteins bind their cognate ligands. In order to demonstrate that the
      fusion proteins have similar ligand binding affinities as the native receptors,
      the affinity constants (Kd) for EPOR, TNFR, IL-4R, and IL-6R-IgG1 fusion proteins
      were measured by surface plasmon resonance and shown to be in good agreement with
      published values. The TNFR-IgG1 fusion protein was employed in a demonstration of
      a novel ELISA format for detecting cytokine receptor binding to cytokine.

PMID- 9758760
TI  - Purification and characterization of a soybean root nodule phosphatase expressed
      in Pichia pastoris.
AB  - Soybean root nodules possess a developmentally regulated acid phosphatase (ACP)
      that exhibits the highest specificity for purine 5'-nucleoside monophosphates.
      The enzyme is a glycosylated dimer of 28- and 31-kDa subunits, which appear to be
      products of the same gene but differ in posttranslational modifications. In order
      to perform directed mutagenesis and more extensive biochemical characterization,
      a means of producing recombinant ACP was needed. Several attempts were made to
      express ACP in Escherichia coli, but all conditions employed resulted in protein
      that was found entirely in inclusion bodies, and resolubilization experiments
      were unsuccessful. Therefore, the methyltrophic yeast Pichia pastoris was chosen
      as a eukaryotic expression host. The coding sequence of ACP was cloned into the
      pPIC9 vector to create a fusion with the yeast alpha mating factor secretion
      signal. The ACP:pPIC9 construct was integrated into P. pastoris strain GS115.
      Expression of ACP was under the control of an alcohol oxidase methanol-inducible
      promoter. Methanol induction resulted in secretion of ACP to a level of 10 mg/L.
      The recombinant ACP was purified 550-fold to homogeneity by phenyl-Sepharose,
      hydroxyapatite, and MonoS chromatography. The purified enzyme had Km values of
      0.08 and 0.12 for 5'-AMP and 5'-GMP. These values were similar to those obtained
      for the native ACP heterodimer purified from soybean (0.08 and 0.15 mM for 5'-AMP
      and 5'-GMP). The specific activity of the recombinant enzyme for all substrates
      tested was 1.6- to 1.8-fold higher than the values for the purified soybean
      heterodimer.

PMID- 9758761
TI  - Cloning and expression in Escherichia coli of the recombinant his-tagged DNA
      polymerases from Pyrococcus furiosus and Pyrococcus woesei.
AB  - Complete PCR-derived DNA fragments containing the structural genes for DNA
      polymerases of the archaeons Pyrococcus furiosus and Pyrococcus woesei were
      cloned into an expression vector. The clones expressing thermostable His-tagged
      DNA polymerases were selected. The cloned fragments were sequenced. The DNA
      sequences were verified to be authentic by sequencing several clones. The
      nucleotide (nt) sequence revealed that DNA polymerase of P. woesei (Pwo DNA
      polymerase) consists of 775 amino acids and has a molecular weight of 90,566. It
      shows 100% nucleotide identity to the nucleotide sequence of DNA polymerase from
      P. furiosus (Pfu DNA polymerase). The results confirm that nucleotide sequences
      of both archaeons (P. furiosus and P. woesei) are highly similar. The recombinant
      DNA polymerases (His-tagged Pfu and His-tagged Pwo) contained a polyhistidine tag
      at the N-terminus (43 additional amino acids) that allowed single-step isolation
      by Ni-affinity chromatography. We found that recombinant plasmids are toxic or
      unstable in the expressing strain BL21(DE3), even in the absence of the inducing
      agent, IPTG. However, the plasmids were stable in BL21(DE3) containing the pLysS
      plasmid, which suppresses expression prior to induction, and His-tagged proteins
      were expressed upon IPTG addition. The proteins were purified by heat treatment
      (to denature E. coli proteins), followed by metal-affinity chromatography on Ni2+
      Sepharose columns. The enzymes were characterized and displayed high DNA
      polymerase activity and thermostability. This bacterial expression system appears
      to be the method of choice for production of Pfu or Pwo DNA polymerases.

PMID- 9758764
TI  - Volume 13, number 2 (1998), in article no. PT980898, "Bacterial expression and
      characterization of human recombinant apolipoprotein(a) kringle IV type 9," by Fu
      Zon chung, lan-hsin wu, helen T. Lee, william T. Mueller, mark A. Spahr, scott R.
      Eaton, Ye tian, philip D. Settimi, dale L. Oxender, and randy ramharack, pages
      222-228: 

PMID- 9758762
TI  - Purification of active chloroplast sedoheptulose-1,7-bisphosphatase expressed in
      Escherichia coli.
AB  - Sedoheptulose-1,7-bisphosphatase (SBPase) is an enzyme unique to photosynthetic
      organisms and has a key role in regulating the photosynthetic Calvin cycle
      through which nearly all carbon enters the biosphere. This makes SBPase an
      appropriate target for intensive study. We have expressed wheat SBPase in
      Escherichia coli either with or without an N-terminal polyhistidine tag. The
      identity of the recombinant SBPases was confirmed by SDS-PAGE analysis and
      immunological detection with a specific antibody. Recombinant SBPase with a
      polyhistidine tag (His-SBPase) was obtained in soluble, active form and purified
      by one-step metal-chelate chromatography. Like the native enzyme, recombinant His
      SBPase was specific for the substrate sedoheptulose-1,7-bisphosphate and required
      the presence of a reducing agent for activity. Polyclonal antibodies were raised
      against recombinant SBPase and were then used to determine relative levels of the
      enzyme in plant extracts. The availability of large amounts of active recombinant
      SBPase will also allow detailed structural studies by site-directed mutagenesis
      and X-ray crystallography.

PMID- 9758763
TI  - Overexpression of functional hydrolase domain of rat liver 10
      formyltetrahydrofolate dehydrogenase in Escherichia coli.
AB  - Rat liver 10-formyltetrahydrofolate dehydrogenase (FDH) is a tetrameric enzyme
      composed of four identical 902-amino-acid-residue (99 kDa) monomers. We expressed
      the enzyme and its 310-amino-acid-residue amino-terminal domain, which is 10
      formyltetrahydrofolate hydrolase, in Escherichia coli BL21 (DE3) cells using the
      pRSET expression vector. We removed the entire translated region of the vector
      including the polyhistidyl tag and the recombinant proteins were expressed, not
      as a fusion constructs, but as unmodified sequences. The expressed full-length
      enzyme was found to be an insoluble protein and was not purified and
      characterized, while the amino-terminal domain was expressed as a soluble protein
      possessing hydrolase activity. The recombinant amino-terminal domain was purified
      in one step on a DEAE MemSep 1000 HP Ion-Exchange Membrane Chromatography
      Cartridge (Millipore) using a ConSep LC100 chromatographic system (Millipore).
      The chromatography gave a homogenous and active preparation of the recombinant
      protein with a yield of about 2 mg per 100 ml of bacterial culture. Kinetic
      parameters of the hydrolase reaction displayed by the amino-terminal domain
      expressed in E. coli were similar to those of the recombinant full-length enzyme
      and its amino-terminal domain previously expressed in insect cells. The purified
      recombinant enzyme remained active for at least 4 weeks at 4 degreesC. These
      results show that the hydrolase amino-terminal domain of FDH can be overexpressed
      as a functional enzyme in E. coli cells and purified in one step by a simple
      chromatographic procedure.

PMID- 9758766
TI  - c-type cytochromes and manganese oxidation in Pseudomonas putida MnB1.
AB  - Pseudomonas putida MnB1 is an isolate from an Mn oxide-encrusted pipeline that
      can oxidize Mn(II) to Mn oxides. We used transposon mutagenesis to construct
      mutants of strain MnB1 that are unable to oxidize manganese, and we characterized
      some of these mutants. The mutants were divided into three groups: mutants
      defective in the biogenesis of c-type cytochromes, mutants defective in genes
      that encode key enzymes of the tricarboxylic acid cycle, and mutants defective in
      the biosynthesis of tryptophan. The mutants in the first two groups were
      cytochrome c oxidase negative and did not contain c-type cytochromes. Mn(II)
      oxidation capability could be recovered in a c-type cytochrome biogenesis
      defective mutant by complementation of the mutation.

PMID- 9758767
TI  - The cytochrome c maturation operon is involved in manganese oxidation in
      Pseudomonas putida GB-1.
AB  - A Pseudomonas putida strain, strain GB-1, oxidizes Mn2+ to Mn oxide in the early
      stationary growth phase. It also secretes a siderophore (identified as
      pyoverdine) when it is subjected to iron limitation. After transposon (Tn5)
      mutagenesis several classes of mutants with differences in Mn2+ oxidation and/or
      secretion of the Mn2+-oxidizing activity were identified. Preliminary analysis of
      the Tn5 insertion site in one of the nonoxidizing mutants suggested that a
      multicopper oxidase-related enzyme is involved in Mn2+ oxidation. The insertion
      site in another mutant was preliminarily identified as a gene involved in the
      general protein secretion pathway. Two mutants defective in Mn2+-oxidizing
      activity also secreted porphyrins into the medium and appeared to be derepressed
      for pyoverdine production. These strains were chosen for detailed analysis. Both
      mutants were shown to contain Tn5 insertions in the ccmF gene, which is part of
      the cytochrome c maturation operon. They were cytochrome oxidase negative and did
      not contain c-type cytochromes. Complementation with part of the ccm operon
      isolated from the wild type restored the phenotype of the parent strain. These
      results indicate that a functional ccm operon is required for Mn2+ oxidation in
      P. putida GB-1. A possible relationship between porphyrin secretion resulting
      from the ccm mutation and stimulation of pyoverdine production is discussed.

PMID- 9758768
TI  - Secondary metabolite- and endochitinase-dependent antagonism toward plant
      pathogenic microfungi of pseudomonas fluorescens isolates from sugar beet
      rhizosphere 
AB  - Forty-seven isolates representing all biovars of Pseudomonas fluorescens (biovars
      I to VI) were collected from the rhizosphere of field-grown sugar beet plants to
      select candidate strains for biological control of preemergence damping-off
      disease. The isolates were tested for in vitro antagonism toward the plant
      pathogenic microfungi Pythium ultimum and Rhizoctonia solani in three different
      plate test media. Mechanisms of fungal inhibition were elucidated by tracing
      secondary-metabolite production and cell wall-degrading enzyme activity in the
      same media. Most biovars expressed a specific mechanism of antagonism, as
      represented by a unique antibiotic or enzyme production in the media. A
      lipopeptide antibiotic, viscosinamide, was produced independently of medium
      composition by P. fluorescens bv. I, whereas the antibiotic 2, 4
      diacetylphloroglucinol was observed only in glucose-rich medium and only in P.
      fluorescens bv. II/IV. Both pathogens were inhibited by the two antibiotics.
      Finally, in low-glucose medium, a cell wall-degrading endochitinase activity in
      P. fluorescens bv. I, III, and VI was the apparent mechanism of antagonism toward
      R. solani. The viscosinamide-producing DR54 isolate (bv. I) was shown to be an
      effective candidate for biological control, as tested in a pot experiment with
      sugar beet seedlings infested with Pythium ultimum. The assignment of different
      patterns of fungal antagonism to the biovars of P. fluorescens is discussed in
      relation to an improved selection protocol for candidate strains to be used in
      biological control.

PMID- 9758769
TI  - Leaching of zinc sulfide by thiobacillus ferrooxidans: experiments with a
      controlled redox potential indicate No direct bacterial mechanism 
AB  - The role of Thiobacillus ferrooxidans in bacterial leaching of mineral sulfides
      is controversial. Much of the controversy is due to the fact that the solution
      conditions, especially the concentrations of ferric and ferrous ions, change
      during experiments. The role of the bacteria would be more easily discernible if
      the concentrations of ferric and ferrous ions were maintained at set values
      throughout the experimental period. In this paper we report results obtained by
      using the constant redox potential apparatus described previously (P. I. Harvey
      and F. K. Crundwell, Appl. Environ. Microbiol. 63:2586-2592, 1997). This
      apparatus is designed to control the redox potential in the leaching compartment
      of an electrolytic cell by reduction or oxidation of dissolved iron. By
      controlling the redox potential the apparatus maintains the concentrations of
      ferrous and ferric ions at their initial values. Experiments were conducted in
      the presence of T. ferrooxidans and under sterile conditions. Analysis of the
      conversion of zinc sulfide in the absence of the bacteria and analysis of the
      conversion of zinc sulfate in the presence of the bacteria produced the same
      results. This indicates that the only role of the bacteria under the conditions
      used is regeneration of ferric ions in solution. In this work we found no
      evidence that there is a direct mechanism for bacterial leaching.

PMID- 9758770
TI  - Thermocrinis ruber gen. nov., sp. nov., A pink-filament-forming hyperthermophilic
      bacterium isolated from yellowstone national park 
AB  - A novel hyperthermophilic bacterium was isolated from pink filamentous streamers
      (pink filaments) occurring in the upper outflow channel (temperature, 82 to 88
      degreesC) of Octopus Spring in Yellowstone National Park, Wyo. The gram-negative
      cells grew at low salinity at temperatures up to 89 degreesC in the neutral to
      alkaline pH range. Depending on the culture conditions, the organisms occurred as
      single motile rods, as aggregates, or as long filaments that formed streamer-like
      cell masses. The novel isolate grew chemolithoautotrophically with hydrogen,
      thiosulfate, and elemental sulfur as electron donors and oxygen as the electron
      acceptor. Alternatively, under aerobic conditions, formate and formamide served
      as sole energy and carbon sources. The novel isolate had a 16S rRNA sequence
      closely related to the 16S rRNA sequence obtained from uncultivated pink
      filaments. It represents a new genus in the order Aquificales, the type species
      of which we name Thermocrinis ruber (type strain, OC 1/4 [= DSM 12173]).

PMID- 9758771
TI  - Effects of pH and oxygen and ammonium concentrations on the community structure
      of nitrifying bacteria from wastewater 
AB  - Shifts in nitrifying community structure and function in response to different
      ammonium concentrations (50, 500, 1,000, and 3,000 mg of N liter-1), pH values
      (pH 6.0, 7.0, and 8.2), and oxygen concentrations (1, 7, and 21%) were studied in
      experimental reactors inoculated with nitrifying bacteria from a wastewater
      treatment plant. The abilities of the communities selected for these conditions
      to regain their original structures after conditions were returned to the
      original conditions were also determined. Changes in nitrifying community
      structure were determined by performing an amplified ribosomal DNA (rDNA)
      restriction analysis of PCR products obtained with ammonia oxidizer-specific rDNA
      primers, by phylogenetic probing, by small-subunit (SSU) rDNA sequencing, and by
      performing a cellular fatty acid analysis. Digestion of ammonia-oxidizer SSU rDNA
      with five restriction enzymes showed that a high ammonium level resulted in a
      great community structure change that was reversible once the ammonium
      concentration was returned to its original level. The smaller changes in
      community structure brought about by the two pH extremes, however, were
      irreversible. Sequence analysis revealed that the highest ammonium environment
      stimulated growth of a nitrifier strain that exhibited 92.6% similarity in a
      partial SSU rRNA sequence to its nearest relative, Nitrosomonas eutropha C-91,
      although the PCR product did not hybridize with a general phylogenetic probe for
      ammonia oxidizers belonging to the beta subgroup of the class Proteobacteria. A
      principal-component analysis of fatty acid methyl ester data detected changes
      from the starter culture in all communities under the new selective conditions,
      but after the standard conditions were restored, all communities produced the
      original fatty acid profiles.

PMID- 9758772
TI  - Effects of temperature, salinity, and medium composition on compatible solute
      accumulation by thermococcus spp 
AB  - The effects of salinity and growth temperature on the accumulation of
      intracellular organic solutes were examined by nuclear magnetic resonance
      spectroscopy (NMR) in Thermococcus litoralis, Thermococcus celer, Thermococcus
      stetteri, and Thermococcus zilligii (strain AN1). In addition, the effects of
      growth stage and composition of the medium were studied in T. litoralis. A novel
      compound identified as beta-galactopyranosyl-5-hydroxylysine was detected in T.
      litoralis grown on peptone-containing medium. Besides this newly discovered
      compound, T. litoralis accumulated mannosylglycerate, aspartate, alpha-glutamate,
      di-myo-inositol-1,1'(3,3')-phosphate, hydroxyproline, and trehalose. The
      hydroxyproline and beta-galactopyranosyl-5-hydroxylysine were probably derived
      from peptone, while the trehalose was derived from yeast extract; none of these
      three compounds was detected in the other Thermococcus strains examined. Di-myo
      inositol-1,1'(3,3')-phosphate, aspartate, and mannosylglycerate were detected in
      T. celer and T. stetteri, and the latter organism also accumulated alpha
      glutamate. The only nonmarine species studied, T. zilligii, accumulated very low
      levels of alpha-glutamate and aspartate. The levels of mannosylglycerate and
      aspartate increased in T. litoralis, T. celer, and T. stetteri in response to
      salt stress, while di-myo-inositol-1,1'(3,3')-phosphate was the major
      intracellular solute at supraoptimal growth temperatures. The phase of growth had
      a strong influence on the types and levels of compatible solutes in T. litoralis;
      mannosylglycerate and aspartate were the major solutes during exponential growth,
      while di-myo-inositol-1,1'(3,3')-phosphate was the predominant organic solute
      during the stationary phase of growth. This work revealed an unexpected ability
      of T. litoralis to scavenge suitable components from the medium and to use them
      as compatible solutes.

PMID- 9758773
TI  - Two intracellular symbiotic bacteria from the mulberry psyllid Anomoneura mori
      (Insecta, Homoptera).
AB  - We characterized the intracellular symbiotic bacteria of the mulberry psyllid
      Anomoneura mori by performing a molecular phylogenetic analysis combined with in
      situ hybridization. In its abdomen, the psyllid has a large, yellow, bilobed
      mycetome (or bacteriome) which consists of many round uninucleated mycetocytes
      (or bacteriocytes) enclosing syncytial tissue. The mycetocytes and syncytium
      harbor specific intracellular bacteria, the X-symbionts and Y-symbionts,
      respectively. Almost the entire length of the bacterial 16S ribosomal DNA (rDNA)
      was amplified and cloned from the whole DNA of A. mori, and two clones, the A
      type and B-type clones, were identified by restriction fragment length
      polymorphism analysis. In situ hybridization with specific oligonucleotide probes
      demonstrated that the A-type and B-type 16S rDNAs were derived from the X
      symbionts and Y-symbionts, respectively. Molecular phylogenetic analyses of the
      16S rDNA sequences showed that these symbionts belong to distinct lineages in the
      gamma subdivision of the Proteobacteria. No 16S rDNA sequences in the databases
      were closely related to the 16S rDNA sequences of the X- and Y-symbionts.
      However, the sequences that were relatively closely related to them were the
      sequences of endosymbionts of other insects. The nucleotide compositions of the
      16S rDNAs of the X- and Y-symbionts were highly AT biased, and the sequence of
      the X-symbiont was the most AT-rich bacterial 16S rDNA sequence reported so far.

PMID- 9758774
TI  - Purification, characterization, and substrate specificity of a novel highly
      glucose-tolerant beta-glucosidase from Aspergillus oryzae.
AB  - Aspergillus oryzae was found to secrete two distinct beta-glucosidases when it
      was grown in liquid culture on various substrates. The major form had a molecular
      mass of 130 kDa and was highly inhibited by glucose. The minor form, which was
      induced most effectively on quercetin (3,3',4',5,7-pentahydroxyflavone)-rich
      medium, represented no more than 18% of total beta-glucosidase activity but
      exhibited a high tolerance to glucose inhibition. This highly glucose-tolerant
      beta-glucosidase (designated HGT-BG) was purified to homogeneity by ammonium
      sulfate precipitation, gel filtration, and anion-exchange chromatography. HGT-BG
      is a monomeric protein with an apparent molecular mass of 43 kDa and a pI of 4.2
      as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and
      isoelectric focusing polyacrylamide gel electrophoresis, respectively. Using p
      nitrophenyl-beta-D-glucoside as the substrate, we found that the enzyme was
      optimally active at 50 degreesC and pH 5.0 and had a specific activity of 1,066
      micromol min-1 mg of protein-1 and a Km of 0.55 mM under these conditions. The
      enzyme is particularly resistant to inhibition by glucose (Ki, 1. 36 M) or
      glucono-delta-lactone (Ki, 12.5 mM), another powerful beta-glucosidase inhibitor
      present in wine. A comparison of the enzyme activities on various glycosidic
      substrates indicated that HGT-BG is a broad-specificity type of fungal beta
      glucosidase. It exhibits exoglucanase activity and hydrolyzes (1-->3)- and (1-
      >6)-beta-glucosidic linkages most effectively. This enzyme was able to release
      flavor compounds, such as geraniol, nerol, and linalol, from the corresponding
      monoterpenyl-beta-D-glucosides in a grape must (pH 2.9, 90 g of glucose liter-1).
      Other flavor precursors (benzyl- and 2-phenylethyl-beta-D-glucosides) and prunin
      (4',5,7-trihydroxyflavanone-7-glucoside), which contribute to the bitterness of
      citrus juices, are also substrates of the enzyme. Thus, this novel beta
      glucosidase is of great potential interest in wine and fruit juice processing
      because it releases aromatic compounds from flavorless glucosidic precursors.

PMID- 9758775
TI  - The transcriptional activator XlnR regulates both xylanolytic and endoglucanase
      gene expression in Aspergillus niger.
AB  - The expression of genes encoding enzymes involved in xylan degradation and two
      endoglucanases involved in cellulose degradation was studied at the mRNA level in
      the filamentous fungus Aspergillus niger. A strain with a loss-of-function
      mutation in the xlnR gene encoding the transcriptional activator XlnR and a
      strain with multiple copies of this gene were investigated in order to define
      which genes are controlled by XlnR. The data presented in this paper show that
      the transcriptional activator XlnR regulates the transcription of the xlnB, xlnC,
      and xlnD genes encoding the main xylanolytic enzymes (endoxylanases B and C and
      beta-xylosidase, respectively). Also, the transcription of the genes encoding the
      accessory enzymes involved in xylan degradation, including alpha-glucuronidase A,
      acetylxylan esterase A, arabinoxylan arabinofuranohydrolase A, and feruloyl
      esterase A, was found to be controlled by XlnR. In addition, XlnR also activates
      transcription of two endoglucanase-encoding genes, eglA and eglB, indicating that
      transcriptional regulation by XlnR goes beyond the genes encoding xylanolytic
      enzymes and includes regulation of two endoglucanase-encoding genes.

PMID- 9758776
TI  - Study of toxin production by isolates of Stachybotrys chartarum and Memnoniella
      echinata isolated during a study of pulmonary hemosiderosis in infants.
AB  - A cluster of cases of pulmonary hemosiderosis among infants was reported in
      Cleveland, Ohio, during 1993 and 1994. These unusual cases appeared only in
      infants ranging in age from 1 to 8 months and were characterized by pulmonary
      hemorrhage, which caused the babies to cough up blood. A case-control study
      identified major home water damage (from plumbing leaks, roof leaks, or flooding)
      as a risk factor for development of pulmonary hemorrhage in these infants.
      Because of an interest in the possibility that trichothecene mycotoxins might be
      involved in this illness, a number of isolates of Stachybotrys chartarum were
      grown in the laboratory on rice, and extracts were prepared and analyzed both for
      cytotoxicity and for specific toxins. Two isolates of Memnoniella echinata, a
      fungus closely related to S. chartarum, were also included in these studies. S.
      chartarum isolates collected from the homes were shown to produce a number of
      highly toxic compounds, and the profiles of toxic compounds from M. echinata were
      similar; the most notable difference was the fact that the principal metabolites
      produced by M. echinata were griseofulvins.

PMID- 9758777
TI  - Analysis of the gene cluster encoding toluene/o-xylene monooxygenase from
      Pseudomonas stutzeri OX1.
AB  - The toluene/o-xylene monooxygenase cloned from Pseudomonas stutzeri OX1 displays
      a very broad range of substrates and a very peculiar regioselectivity, because it
      is able to hydroxylate more than one position on the aromatic ring of several
      hydrocarbons and phenols. The nucleotide sequence of the gene cluster coding for
      this enzymatic system has been determined. The sequence analysis revealed the
      presence of six open reading frames (ORFs) homologous to other genes clustered in
      operons coding for multicomponent monooxygenases found in benzene- and toluene
      degradative pathways cloned from Pseudomonas strains. Significant similarities
      were also found with multicomponent monooxygenase systems for phenol, methane,
      alkene, and dimethyl sulfide cloned from different bacterial strains. The
      knockout of each ORF and complementation with the wild-type allele indicated that
      all six ORFs are essential for the full activity of the toluene/o-xylene
      monooxygenase in Escherichia coli. This analysis also shows that despite its
      activity on both hydrocarbons and phenols, toluene/ o-xylene monooxygenase
      belongs to a toluene multicomponent monooxygenase subfamily rather than to the
      monooxygenases active on phenols.

PMID- 9758779
TI  - Intracellular changes in ions and organic solutes in halotolerant brevibacterium
      sp. Strain JCM 6894 after exposure to hyperosmotic shock 
AB  - In the present study we aimed to observe the intracellular responses when there
      was a hyperosmotic shock with a large shift in ionic strength in nutrient-rich
      and nutrient-poor external environments in order to clarify the availability of
      substrates. To do this, we used the halotolerant organism Brevibacterium sp.
      strain JCM 6894, which is able to grow in the presence of a wide range of salt
      concentrations. Hyperosmotic shock was induced by transferring cells in the late
      exponential phase of growth in a complex medium containing 0.5 M NaCl into either
      old or fresh culture medium containing 2 M NaCl. Changes in the growth rate, in
      the pH of the medium, and in the internal cation or organic solute concentrations
      in the cytosol after an upshock were analyzed as a function of incubation time.
      The cells exhibited very different responses to upshocks in fresh culture medium
      and in old culture medium; in fresh culture medium, growth was stimulated and the
      medium became more acidic, whereas the old culture medium repressed growth and
      the medium became more alkaline. The intracellular free Na+ concentrations
      remained low (80 nmol mg of protein-1) after an upshock in fresh culture medium,
      although they quickly increased twofold in the old culture medium. In contrast,
      K+ ions immediately accumulated in the cells in fresh culture medium, whereas K+
      ions were taken up quite slowly in old culture medium. Furthermore, the cells
      placed in fresh culture medium transiently accumulated alanine and glutamine in
      response to the upshock, but the cells placed in old culture medium did not.
      Growth of the Brevibacterium strain at higher levels of salinity was supported by
      ectoine synthesis but was not observed after the shift to high-osmolarity
      conditions in the old culture. In the fresh culture, however, ectoine was
      vigorously synthesized in cells for more than 5 h after the upshock; the
      concentration of ectoine in cells was more than 3,500 nmol mg of protein-1 at 10
      h, which corresponded to a ninefold increase compared to the concentration before
      the shock. These findings are consistent with the results of an analysis of the
      extracellular medium composition before and after the upshock.

PMID- 9758778
TI  - Plasmids responsible for horizontal transfer of naphthalene catabolism genes
      between bacteria at a coal tar-contaminated site are homologous to pDTG1 from
      pseudomonas putida NCIB 9816-4 
AB  - The presence of a highly conserved nahAc allele among phylogenetically diverse
      bacteria carrying naphthalene-catabolic plasmids provided evidence for in situ
      horizontal gene transfer at a coal tar-contaminated site (J. B. Herrick, K. G.
      Stuart-Keil, W. C. Ghiorse, and E. L. Madsen, Appl. Environ. Microbiol. 63:2330
      2337, 1997). The objective of the present study was to identify and characterize
      the different-sized naphthalene-catabolic plasmids in order to determine the
      probable mechanism of horizontal transfer of the nahAc gene in situ. Filter
      matings between naphthalene-degrading bacterial isolates and their cured progeny
      revealed that the naphthalene-catabolic plasmids were self-transmissible. Limited
      interstrain transfer was also found. Analysis of the restriction fragment length
      polymorphism (RFLP) patterns indicated that catabolic plasmids from 12 site
      derived isolates were closely related to each other and to the naphthalene
      catabolic plasmid (pDTG1) of Pseudomonas putida NCIB 9816-4, which was isolated
      decades ago in Bangor, Wales. The similarity among all site-derived naphthalene
      catabolic plasmids and pDTG1 was confirmed by using the entire pDTG1 plasmid as a
      probe in Southern hybridizations. Two distinct but similar naphthalene-catabolic
      plasmids were retrieved directly from the microbial community indigenous to the
      contaminated site in a filter mating by using a cured, rifampin-resistant site
      derived isolate as the recipient. RFLP patterns and Southern hybridization showed
      that both of these newly retrieved plasmids, like the isolate-derived plasmids,
      were closely related to pDTG1. These data indicate that a pDTG1-like plasmid is
      the mobile genetic element responsible for transferring naphthalene-catabolic
      genes among bacteria in situ. The pervasiveness and persistence of this
      naphthalene-catabolic plasmid suggest that it may have played a role in the
      adaptation of this microbial community to the coal tar contamination at our study
      site.

PMID- 9758780
TI  - Vibrio cholerae O1 strain TSI-4 produces the exopolysaccharide materials that
      determine colony morphology, stress resistance, and biofilm formation.
AB  - Vibrio cholerae O1 strain TSI-4 (El Tor, Ogawa) can shift to a rugose colony
      morphology from its normal translucent colony morphology in response to nutrient
      starvation. We have investigated differences between the rugose and translucent
      forms of V. cholerae O1 strain TSI-4. Electron microscopic examination of the
      rugose form of TSI-4 (TSI-4/R) revealed thick, electron-dense exopolysaccharide
      materials surrounding polycationic ferritin-stained cells, while the ferritin
      stained material was absent around the translucent form of TSI-4 (TSI-4/T). The
      exopolysaccharide produced by V. cholerae TSI-4/R was found to have a composition
      of N-acetyl-D-glucosamine, D-mannose, 6-deoxy-D-galactose, and D-galactose
      (7.4:10.2:2.4:3.0). The expression of an amorphous exopolysaccharide promotes
      biofilm development under static culture conditions. Biofilm formation by the
      rugose strain was determined by scanning electron microscopy, and most of the
      surface of the film was colonized by actively dividing rod cells. The
      corresponding rugose and translucent strains were compared for stress resistance.
      By having exopolysaccharide materials, the rugose strains acquired resistance to
      osmotic and oxidative stress. Our data indicated that an exopolysaccharide
      material on the surface of the rugose strain promoted biofilm formation and
      resistance to the effects of two stressing agents.

PMID- 9758782
TI  - A plant growth-promoting bacterium that decreases nickel toxicity in seedlings 
AB  - A plant growth-promoting bacterium, Kluyvera ascorbata SUD165, that contained
      high levels of heavy metals was isolated from soil collected near Sudbury,
      Ontario, Canada. The bacterium was resistant to the toxic effects of Ni2+, Pb2+,
      Zn2+, and CrO4-, produced a siderophore(s), and displayed 1-aminocyclopropane-1
      carboxylic acid deaminase activity. Canola seeds inoculated with this bacterium
      and then grown under gnotobiotic conditions in the presence of high
      concentrations of nickel chloride were partially protected against nickel
      toxicity. In addition, protection by the bacterium against nickel toxicity was
      evident in pot experiments with canola and tomato seeds. The presence of K.
      ascorbata SUD165 had no measurable influence on the amount of nickel accumulated
      per milligram (dry weight) of either roots or shoots of canola plants. Therefore,
      the bacterial plant growth-promoting effect in the presence of nickel was
      probably not attributable to the reduction of nickel uptake by seedlings. Rather,
      it may reflect the ability of the bacterium to lower the level of stress ethylene
      induced by the nickel.

PMID- 9758781
TI  - A bioluminescence assay using Nitrosomonas europaea for rapid and sensitive
      detection of nitrification inhibitors.
AB  - An expression vector for the luxAB genes, derived from Vibrio harveyi, was
      introduced into Nitrosomonas europaea. Although the recombinant strain produced
      bioluminescence due to the expression of the luxAB genes under normal growing
      conditions, the intensity of the light emission decreased immediately, in a time
      and dose-dependent manner, with the addition of ammonia monooxygenase inhibitors,
      such as allylthiourea, phenol, and nitrapyrin. When whole cells were challenged
      with several nitrification inhibitors and toxic compounds, a close relationship
      was found between the change in the intensity of the light emission and the level
      of ammonia-oxidizing activity. The response of bioluminescence to the addition of
      allylthiourea was considerably faster than the change in the ammonia-oxidizing
      rate, measured as both the O2 uptake and NO2- production rates. The
      bioluminescence of cells inactivated by ammonia monooxygenase inhibitor was
      recovered rapidly by the addition of certain substrates for hydroxylamine
      oxidoreductase. These results suggested that the inhibition of bioluminescence
      was caused by the immediate decrease of reducing power in the cell due to the
      inactivation of ammonia monooxygenase, as well as by the destruction of other
      cellular metabolic pathways. We conclude that the assay system using luminous
      Nitrosomonas can be applied as a rapid and sensitive detection test for
      nitrification inhibitors, and it will be used to monitor the nitrification
      process in wastewater treatment plants.

PMID- 9758784
TI  - Application of molecular biological techniques to a seasonal study of ammonia
      oxidation in a eutrophic freshwater lake 
AB  - The autotrophic ammonia-oxidizing bacteria in a eutrophic freshwater lake were
      studied over a 12-month period. Numbers of ammonia oxidisers in the lakewater
      were small throughout the year, and tangential-flow concentration was required to
      obtain meaningful estimates of most probable numbers. Sediments from littoral and
      profundal sites supported comparatively large populations of these bacteria, and
      the nitrification potential was high, particularly in summer samples from the
      littoral sediment surface. In enrichment cultures, lakewater samples nitrified at
      low (0.67 mM) ammonium concentrations only whereas sediment samples exhibited
      nitrification at high (12.5 mM) ammonium concentrations also. Enrichments at low
      ammonium concentration did not nitrify when inoculated into high-ammonium medium,
      but the converse was not true. This suggests that the water column contains a
      population of ammonia oxidizers that is sensitive to high ammonium
      concentrations. The observation of nitrification at high ammonium concentration
      by isolates from some winter lakewater samples, identified as nitrosospiras by
      16S rRNA probing, is consistent with the hypothesis that sediment ammonia
      oxidizers enter the water column at overturn. With only one exception, nested PCR
      amplification enabled the detection of Nitrosospira 16S rDNA in all samples, but
      Nitrosomonas (N. europaea-eutropha lineage) 16S rDNA was never obtained. However,
      the latter were part of the sediment and water column communities, because their
      16S rRNA could be detected by specific oligonucleotide probing of enrichment
      cultures. Furthermore, a specific PCR amplification regime for the Nitrosomonas
      europaea ammonia monooxygenase gene (amoA) yielded positive results when applied
      directly to sediment and lakewater samples. Patterns of Nitrosospira and
      Nitrosomonas detection by 16S rRNA oligonucleotide probing of sediment enrichment
      cultures were complex, but lakewater enrichments at low ammonium concentration
      were positive for nitrosomonads and not nitrosospiras. Analysis of enrichment
      cultures has therefore provided evidence for the existence of subpopulations
      within the lake ammonia-oxidizing community distinguishable on the basis of
      ammonium tolerance and possibly showing a seasonal distribution between the
      sediment and water column.

PMID- 9758783
TI  - Characterization of an extremely thermostable restriction enzyme, PspGI, from a
      Pyrococcus strain and cloning of the PspGI restriction-modification system in
      Escherichia coli.
AB  - An extremely thermostable restriction endonuclease, PspGI, was purified from
      Pyrococcus sp. strain GI-H. PspGI is an isoschizomer of EcoRII and cleaves DNA
      before the first C in the sequence 5' CCWGG 3' (W is A or T). PspGI digestion can
      be carried out at 65 to 85 degrees C. To express PspGI at high levels, the PspGI
      restriction-modification genes (pspGIR and pspGIM) were cloned in Escherichia
      coli. M.PspGI contains the conserved sequence motifs of alpha
      aminomethyltransferases; therefore, it must be an N4-cytosine methylase. M.PspGI
      shows 53% similarity to (44% identity with) its isoschizomer, M.MvaI from
      Micrococcus variabilis. In a segment of 87 amino acid residues, PspGI shows
      significant sequence similarity to EcoRII and to regions of SsoII and StyD4I
      which have a closely related recognition sequence (5' CCNGG 3'). PspGI was
      expressed in E. coli via a T7 expression system. Recombinant PspGI was purified
      to near homogeneity and had a half-life of 2 h at 95 degrees C. PspGI remained
      active following 30 cycles of thermocycling; thus, it can be used in DNA-based
      diagnostic applications.

PMID- 9758786
TI  - Ellipsometric measurement of bacterial films at metal-electrolyte interfaces
AB  - Ellipsometric measurements were used to monitor the formation of a bacterial cell
      film on polarized metal surfaces (Al-brass and Ti). Under cathodic polarization
      bacterial attachment was measured from changes in the ellipsometric angles. These
      were fitted to an effective medium model for a nonabsorbing bacterial film with
      an effective refractive index (nf) of 1.38 and a thickness (df) of 160 +/- 10 nm.
      From the optical measurements a surface coverage of 17% was estimated, in
      agreement with direct microscopic observations. The influence of bacteria on the
      formation of oxide films was monitored by ellipsometry following the film growth
      in situ. A strong inhibition of metal oxide film formation was observed, which
      was assigned to the decrease in oxygen concentration due to the presence of
      bacteria. It is shown that the irreversible adhesion of bacteria to the surface
      can be monitored ellipsometrically. Electrophoretic mobility is proposed as one
      of the factors determining bacterial attachment. The high sensitivity of
      ellipsometry and its usefulness for the determination of growth of interfacial
      bacterial films is demonstrated.

PMID- 9758785
TI  - Estimation of the relative abundance of different Bacteroides and Prevotella
      ribotypes in gut samples by restriction enzyme profiling of PCR-amplified 16S
      rRNA gene sequences.
AB  - We describe an approach for determining the genetic composition of Bacteroides
      and Prevotella populations in gut contents based on selective amplification of
      16S rRNA gene sequences (rDNA) followed by cleavage of the amplified material
      with restriction enzymes. The relative contributions of different ribotypes to
      total Bacteroides and Prevotella 16S rDNA are estimated after end labelling of
      one of the PCR primers, and the contribution of Bacteroides and Prevotella
      sequences to total eubacterial 16S rDNA is estimated by measuring the binding of
      oligonucleotide probes to amplified DNA. Bacteroides and Prevotella 16S rDNA
      accounted for between 12 and 62% of total eubacterial 16S rDNA in samples of
      ruminal contents from six sheep and a cow. Ribotypes 4, 5, 6, and 7, which
      include most cultivated rumen Prevotella strains, together accounted for between
      20 and 86% of the total amplified Bacteroides and Prevotella rDNA in these
      samples. The most abundant Bacteroides or Prevotella ribotype in four animals,
      however, was ribotype 8, for which there is only one known cultured isolate,
      while ribotypes 1 and 2, which include many colonic Bacteroides spp., were the
      most abundant in two animals. This indicates that some abundant Bacteroides and
      Prevotella groups in the rumen are underrepresented among cultured rumen
      Prevotella isolates. The approach described here provides a rapid, convenient,
      and widely applicable method for comparing the genotypic composition of bacterial
      populations in gut samples.

PMID- 9758787
TI  - Optimization of differential display of prokaryotic mRNA: application to pure
      culture and soil microcosms.
AB  - The differential display (DD) technique, which is widely used almost exclusively
      for eukaryotic gene discovery, was optimized to detect differential mRNA
      transcription from both pure-culture and soil-derived bacterial RNA. A model
      system which included toluene induction of todC1 in Pseudomonas putida F1 was
      used to optimize the procedure. At 24-h tod induction was determined to be
      approximately 8 x 10(7) transcripts/microg or 0.08% of the total mRNA. The primer
      concentration, primer length, annealing temperature, and template,
      deoxynucleoside triphosphate, and MgCl2 concentrations were varied to optimize
      amplification of a todC1 fragment. The limit of detection of todC1 by DD was
      found to be 0.015 ng of total RNA template or approximately 10(3) transcripts.
      Once optimized, a todC1C2 gene fragment from P. putida F1 RNA was detected by
      using an arbitrary primer for the reverse transcriptase step in conjunction with
      the same arbitrary primer and a Shine-Dalgarno primer in the PCR. To verify the
      results, an arbitrary primer was used to detect recovery of a new salicylate
      inducible naphthalene dioxygenase in Burkholderia cepacia JS150. The method was
      then used to detect mRNA induction in both inoculated and uninoculated toluene
      induced soil microcosms. Several putative differentially expressed partial gene
      sequences obtained from the uninoculated microcosms were examined, and one novel
      fragment was found to be differentially expressed.

PMID- 9758788
TI  - Effect of butyrolactone I on the producing fungus, Aspergillus terreus.
AB  - Butyrolactone I [alpha-oxo-beta-(p-hydroxyphenyl)-gamma-(p-hydroxy-m-3, 3
      dimethylallyl-benzyl)-gamma-methoxycarbonyl-gamma-butyrolactone] is produced as a
      secondary metabolite by Aspergillus terreus. Because small butyrolactone
      containing molecules act as self-regulating factors in some bacteria, the effects
      of butyrolactone I on the producing organism were studied; specifically, changes
      in morphology, sporulation, and secondary metabolism were studied. Threefold or
      greater increases in hyphal branching (with concomitant decreases in the average
      hyphal growth unit), submerged sporulation, and secondary metabolism were
      observed when butyrolactone I was added to cultures of A. terreus. Among the
      secondary metabolites whose production was increased by this treatment was the
      therapeutically important compound lovastatin. These findings indicate that
      butyrolactone I induces morphological and sporulation changes in A. terreus and
      enhances secondary metabolite production in a manner similar to that previously
      reported for filamentous bacteria.

PMID- 9758789
TI  - Characterization of aflJ, a gene required for conversion of pathway intermediates
      to aflatoxin.
AB  - The genes encoding the aflatoxin biosynthetic pathway enzymes have been localized
      as a cluster to a 75-kb DNA fragment. The enzymatic functions of the products of
      most of the genes in the cluster are known, but there are a few genes that have
      not yet been characterized. We report here the characterization of one of these
      genes, a gene designated aflJ. This gene resides in the cluster adjacent to the
      pathway regulatory gene, aflR, and the two genes are divergently transcribed.
      Disruption of aflJ in Aspergillus flavus results in a failure to produce
      aflatoxins and a failure to convert exogenously added pathway intermediates
      norsolorinic acid, sterigmatocystin, and O-methylsterigmatocystin to aflatoxin.
      The disrupted strain does, however, accumulate pksA, nor-1, ver-1, and omtA
      transcripts under conditions conducive to aflatoxin biosynthesis. Therefore,
      disruption of aflJ does not affect transcription of these genes, and aflJ does
      not appear to have a regulatory function similar to that of aflR. Sequence
      analysis of aflJ and its putative peptide, AflJ, did not reveal any enzymatic
      domains or significant similarities to proteins of known function. The putative
      peptide does contain three regions predicted to be membrane-spanning domains and
      a microbodies C-terminal targeting signal.

PMID- 9758790
TI  - Regulation of aflR and its product, AflR, associated with aflatoxin biosynthesis.
AB  - We studied the role of the regulatory gene aflR and its product, AflR, in the
      biosynthesis of aflatoxin in Aspergillus. Western blot and enzyme-linked
      immunosorbent assay analyses revealed that aflatoxin B1 accumulation was directly
      related to AflR expression and was regulated by various environmental and
      nutritional conditions, including temperature, air supply, carbon source,
      nitrogen source, and zinc availability. Expression of an aflatoxin biosynthetic
      pathway structural gene, omtA, was regulated by the presence of AflR. Induction
      patterns for aflR mRNA and AflR were correlated with that for omtA mRNA in an
      aflatoxin-producing strain of Aspergillus parasiticus. Analysis of non-aflatoxin
      producing strains of A. flavus, A. sojae, and A. oryzae grown in medium suitable
      for aflatoxin B1 production showed that both aflR mRNA and AflR production were
      present; however, omtA mRNA production was not detected in any of these examined
      strains. AflR in the A. oryzae strain was regulated by carbon source and
      temperature in a manner similar to that seen with A. parasiticus.

PMID- 9758792
TI  - Structural and functional dynamics of sulfate-reducing populations in bacterial
      biofilms 
AB  - We describe the combined application of microsensors and molecular techniques to
      investigate the development of sulfate reduction and of sulfate-reducing
      bacterial populations in an aerobic bacterial biofilm. Microsensor measurements
      for oxygen showed that anaerobic zones developed in the biofilm within 1 week and
      that oxygen was depleted in the top 200 to 400 &mgr;m during all stages of
      biofilm development. Sulfate reduction was first detected after 6 weeks of
      growth, although favorable conditions for growth of sulfate-reducing bacteria
      (SRB) were present from the first week. In situ hybridization with a 16S rRNA
      probe for SRB revealed that sulfate reducers were present in high numbers
      (approximately 10(8) SRB/ml) in all stages of development, both in the oxic and
      anoxic zones of the biofilm. Denaturing gradient gel electrophoresis (DGGE)
      showed that the genetic diversity of the microbial community increased during the
      development of the biofilm. Hybridization analysis of the DGGE profiles with
      taxon-specific oligonucleotide probes showed that Desulfobulbus and Desulfovibrio
      were the main sulfate-reducing bacteria in all biofilm samples as well as in the
      bulk activated sludge. However, different Desulfobulbus and Desulfovibrio species
      were found in the 6th and 8th weeks of incubation, respectively, coinciding with
      the development of sulfate reduction. Our data indicate that not all SRB detected
      by molecular analysis were sulfidogenically active in the biofilm.

PMID- 9758791
TI  - Bias in template-to-product ratios in multitemplate PCR.
AB  - Bias introduced by the simultaneous amplification of specific genes from complex
      mixtures of templates remains poorly understood. To explore potential causes and
      the extent of bias in PCR amplification of 16S ribosomal DNAs (rDNAs), genomic
      DNAs of two closely and one distantly related bacterial species were mixed and
      amplified with universal, degenerate primers. Quantification and comparison of
      template and product ratios showed that there was considerable and reproducible
      overamplification of specific templates. Variability between replicates also
      contributed to the observed bias but in a comparatively minor way. Based on these
      initial observations, template dosage and differences in binding energies of
      permutations of the degenerate, universal primers were tested as two likely
      causes of this template-specific bias by using 16S rDNA templates modified by
      site-directed mutagenesis. When mixtures of mutagenized templates containing AT-
      and GC-rich priming sites were used, templates containing the GC-rich permutation
      amplified with higher efficiency, indicating that different primer binding
      energies may to a large extent be responsible for overamplification. In contrast,
      gene copy number was found to be an unlikely cause of the observed bias.
      Similarly, amplification from DNA extracted from a natural community to which
      different amounts of genomic DNA of a single bacterial species were added did not
      affect relative product ratios. Bias was reduced considerably by using high
      template concentrations, by performing fewer cycles, and by mixing replicate
      reaction preparations.

PMID- 9758793
TI  - Colonization of wheat roots by an exopolysaccharide-producing pantoea agglomerans
      strain and its effect on rhizosphere soil aggregation 
AB  - The effect of bacterial secretion of an exopolysaccharide (EPS) on rhizosphere
      soil physical properties was investigated by inoculating strain NAS206, which was
      isolated from the rhizosphere of wheat (Triticum durum L.) growing in a Moroccan
      vertisol and was identified as Pantoea aglomerans. Phenotypic identification of
      this strain with the Biotype-100 system was confirmed by amplified ribosomal DNA
      restriction analysis. After inoculation of wheat seedlings with strain NAS206,
      colonization increased at the rhizoplane and in root-adhering soil (RAS) but not
      in bulk soil. Colonization further increased under relatively dry conditions (20%
      soil water content; matric potential, -0.55 MPa). By means of genetic
      fingerprinting using enterobacterial repetitive intergenic consensus PCR, we were
      able to verify that colonies counted as strain NAS206 on agar plates descended
      from inoculated strain NAS206. The intense colonization of the wheat rhizosphere
      by these EPS-producing bacteria was associated with significant soil aggregation,
      as shown by increased ratios of RAS dry mass to root tissue (RT) dry mass
      (RAS/RT) and the improved water stability of adhering soil aggregates. The
      maximum effect of strain NAS206 on both the RAS/RT ratio and aggregate stability
      was measured at 24% average soil water content (matric potential, -0.20 MPa).
      Inoculated strain NAS206 improved RAS macroporosity (pore diameter, 10 to 30
      &mgr;m) compared to the noninoculated control, particularly when the soil was
      nearly water saturated (matric potential, -0.05 MPa). Our results suggest that P.
      agglomerans NAS206 can play an important role in the regulation of the water
      content (excess or deficit) of the rhizosphere of wheat by improving soil
      aggregation.

PMID- 9758796
TI  - Toxic effects of modified fenton reactions on xanthobacter flavus FB71 
AB  - The toxic effects of modified Fenton reactions on Xanthobacter flavus FB71,
      measured as microbial survival rates, were determined as part of an investigation
      of simultaneous abiotic and biotic oxidations of xenobiotic chemicals. A central
      composite, rotatable experimental design was developed to study the survival
      rates of X. flavus under various concentrations of hydrogen peroxide and iron(II)
      and at different initial cell populations. A model based on the experimental
      results, relating microorganism survival to the variables of peroxide, iron, and
      cellular concentrations was formulated and fit the data reasonably well, with a
      coefficient of determination of 0.76. The results of this study indicate that the
      use of simultaneous abiotic and biotic processes for the treatment of xenobiotic
      compounds may be possible.

PMID- 9758795
TI  - Enhanced utilization of phosphonate and phosphite by Klebsiella aerogenes.
AB  - Klebsiella aerogenes ATCC 9621 was able to utilize phosphonates (Pn), including
      aminoethylphosphonate, ethylphosphonate, methylphosphonate (MPn), and
      phosphonoacetate, and inorganic phosphite (Pt) as sole sources of phosphorus (P).
      The products of the phn gene cluster were absolutely required for Pn breakdown
      and Pt oxidation to inorganic phosphate (Pi) in this organism. To determine if K.
      aerogenes ATCC 9621 could be engineered to enhance the utilization of Pn and Pt,
      a multicopy plasmid, pBI05, which carried the entire phn gene cluster, was
      introduced into this strain. Despite the increased dosage of the phn genes, K.
      aerogenes ATCC 9621(pBI05) could utilize only up to 1.1-fold more Pn and Pt than
      did the control strain with the parent vector alone. These results suggested that
      Pi, which was generated from Pn and Pt, might limit further utilization of these
      P compounds. Consequently, to convert the resulting Pi to polyphosphate (polyP),
      the plasmid pKP28, which carried the K. aerogenes ppk gene (which encodes polyP
      kinase), was introduced into K. aerogenes ATCC 9621(pBI05). Overexpression of the
      ppk gene in K. aerogenes ATCC 9621(pBI05, pKP28) resulted in a 2.5-fold increase
      in Pt utilization over that of the control strain. This recombinant strain also
      accumulated approximately sixfold more P than did the control strain when the
      cells were grown with MPn as a sole source of P.

PMID- 9758794
TI  - Capacity of nine thermostable DNA polymerases To mediate DNA amplification in the
      presence of PCR-inhibiting samples.
AB  - The PCR is an extremely powerful method for detecting microorganisms. However,
      its full potential as a rapid detection method is limited by the inhibition of
      the thermostable DNA polymerase from Thermus aquaticus by many components found
      in complex biological samples. In this study, we have compared the effects of
      known PCR-inhibiting samples on nine thermostable DNA polymerases. Samples of
      blood, cheese, feces, and meat, as well as various ions, were added to PCR
      mixtures containing various thermostable DNA polymerases. The nucleic acid
      amplification capacity of the nine polymerases, under buffer conditions
      recommended by the manufacturers, was evaluated by using a PCR-based detection
      method for Listeria monocytogenes in the presence of purified template DNA and
      different concentrations of PCR inhibitors. The AmpliTaq Gold and the Taq DNA
      polymerases from Thermus aquaticus were totally inhibited in the presence of
      0.004% (vol/vol) blood in the PCR mixture, while the HotTub, Pwo, rTth, and Tfl
      DNA polymerases were able to amplify DNA in the presence of 20% (vol/vol) blood
      without reduced amplification sensitivity. The DNA polymerase from Thermotoga
      maritima (Ultma) was found to be the most susceptible to PCR inhibitors present
      in cheese, feces, and meat samples. When the inhibitory effect of K and Na ions
      was tested on the nine polymerases, HotTub from Thermus flavus and rTth from
      Thermus thermophilus were the most resistant. Thus, the PCR-inhibiting effect of
      various components in biological samples can, to some extent, be eliminated by
      the use of the appropriate thermostable DNA polymerase.

PMID- 9758797
TI  - Xanthan lyase of Bacillus sp. strain GL1 liberates pyruvylated mannose from
      xanthan side chains.
AB  - When the bacterium Bacillus sp. strain GL1 was grown in a medium containing
      xanthan as the carbon source, the viscosity of the medium decreased in
      association with growth, showing that the bacterium had xanthan-depolymerizing
      enzymes. One of the xanthan-depolymerizing enzymes (xanthan lyase) was present in
      the medium and was found to be induced by xanthan. The xanthan lyase purified
      from the culture fluid was a monomer with a molecular mass of 75 kDa, and was
      most active at pH 5.5 and 50 degrees C. The enzyme was highly specific for
      xanthan and produced pyruvylated mannose. The result indicates that the enzyme
      cleaved the linkage between the terminal pyruvylated mannosyl and glucuronyl
      residues in the side chain of xanthan.

PMID- 9758798
TI  - Development of PCR primer systems for amplification of nitrite reductase genes
      (nirK and nirS) to detect denitrifying bacteria in environmental samples.
AB  - A system was developed for the detection of denitrifying bacteria by the
      amplification of specific nitrite reductase gene fragments with PCR. Primer
      sequences were found for the amplification of fragments from both nitrite
      reductase genes (nirK and nirS) after comparative sequence analysis. Whenever
      amplification was tried with these primers, the known nir type of denitrifying
      laboratory cultures could be confirmed. Likewise, the method allowed a
      determination of the nir type of five laboratory strains. The nirK gene could be
      amplified from Blastobacter denitrificans, Alcaligenes xylosoxidans, and
      Alcaligenes sp. (DSM 30128); the nirS gene was amplified from Alcaligenes
      eutrophus DSM 530 and from the denitrifying isolate IFAM 3698. For each of the
      two genes, at least one primer combination amplified successfully for all of the
      test strains. Specific amplification products were not obtained with
      nondenitrifying bacteria or with strains of the other nir type. The specificity
      of the amplified products was confirmed by subsequent sequencing. These results
      suggest the suitability of the method for the qualitative detection of
      denitrifying bacteria in environmental samples. This was shown by applying one
      generally amplifying primer combination for each nir gene developed in this study
      to total DNA preparations from aquatic habitats.

PMID- 9758799
TI  - Distribution and life strategies of two bacterial populations in a eutrophic lake
AB  - Monoclonal antibodies and epifluorescence microscopy were used to determine the
      depth distribution of two indigenous bacterial populations in the stratified Lake
      Plusssee and characterize their life strategies. Populations of Comamonas
      acidovorans PX54 showed a depth distribution with maximum abundances in the oxic
      epilimnion, whereas Aeromonas hydrophila PU7718 showed a depth distribution with
      maximum abundances in the anoxic thermocline layer (metalimnion), i. e., in the
      water layer with the highest microbial activity. Resistance of PX54 to protist
      grazing and high metabolic versatility and growth rate of PU7718 were the most
      important life strategy traits for explaining the depth distribution of the two
      bacterial populations. Maximum abundance of PX54 was 16,000 cells per ml, and
      maximum abundance of PU7718 was 20,000 cells per ml. Determination of bacterial
      productivity in dilution cultures with different-size fractions of dissolved
      organic matter (DOM) from lake water indicates that low-molecular-weight (LMW)
      DOM is less bioreactive than total DOM (TDOM). The abundance and growth rate of
      PU7718 were highest in the TDOM fractions, whereas those of PX54 were highest in
      the LMW DOM fraction, demonstrating that PX54 can grow well on the less
      bioreactive DOM fraction. We estimated that 13 to 24% of the entire bacterial
      community and 14% of PU7718 were removed by viral lysis, whereas no significant
      effect of viral lysis on PX54 could be detected. Growth rates of PX54 (0.11 to
      0.13 h-1) were higher than those of the entire bacterial community (0.04 to 0.08
      h-1) but lower than those of PU7718 (0.26 to 0.31 h-1). In undiluted cultures,
      the growth rates were significantly lower, pointing to density effects such as
      resource limitation or antibiosis, and the effects were stronger for PU7718 and
      the entire bacterial community than for PX54. Life strategy characterizations
      based on data from literature and this study revealed that the fast-growing and
      metabolically versatile A. hydrophila PU7718 is an r-strategist or opportunistic
      population in Lake Plusssee, whereas the grazing-resistant C. acidovorans PX54 is
      rather a K-strategist or equilibrium population.

PMID- 9758801
TI  - Manganese reduction by microbes from oxic regions of the lake vanda (Antarctica)
      water column 
AB  - Depth profiles of metals in Lake Vanda, a permanently ice-covered, stratified
      Antarctic lake, suggest the importance of particulate manganese oxides in the
      scavenging, transport, and release of metals. Since manganese oxides can be
      solubilized by manganese-reducing bacteria, microbially mediated manganese
      reduction was investigated in Lake Vanda. Microbes concentrated from oxic regions
      of the water column, encompassing a peak of soluble manganese [Mn(II)], reduced
      synthetic manganese oxides (MnO2) when incubated aerobically. Pure cultures of
      manganese-reducing bacteria were readily isolated from waters collected near the
      oxic Mn(II) peak. Based on phylogenetic analysis of the 16S rRNA gene sequence,
      most of the isolated manganese reducers belong to the genus Carnobacterium.
      Cultures of a phylogenetically representative strain of Carnobacterium reduced
      synthetic MnO2 in the presence of sodium azide, as was seen in field assays.
      Unlike anaerobes that utilize manganese oxides as terminal electron acceptors in
      respiration, isolates of the genus Carnobacterium reduced Mn(IV) via a diffusible
      compound under oxic conditions. The release of adsorbed trace metals accompanying
      the solubilization of manganese oxides may provide populations of Carnobacterium
      with a source of nutrients in this extremely oligotrophic environment.

PMID- 9758800
TI  - Biocatalyst engineering by assembly of fatty acid transport and oxidation
      activities for In vivo application of cytochrome P-450BM-3 monooxygenase.
AB  - The application of whole cells containing cytochrome P-450BM-3 monooxygenase [EC
      1.14.14.1] for the bioconversion of long-chain saturated fatty acids to omega-1,
      omega-2, and omega-3 hydroxy fatty acids was investigated. We utilized
      pentadecanoic acid and studied its conversion to a mixture of 12-, 13-, and 14
      hydroxypentadecanoic acids by this monooxygenase. For this purpose, Escherichia
      coli recombinants containing plasmid pCYP102 producing the fatty acid
      monooxygenase cytochrome P-450BM-3 were used. To overcome inefficient uptake of
      pentadecanoic acid by intact E. coli cells, we made use of a cloned fatty acid
      uptake system from Pseudomonas oleovorans which, in contrast to the common FadL
      fatty acid uptake system of E. coli, does not require coupling by FadD (acyl
      coenzyme A synthetase) of the imported fatty acid to coenzyme A. This system from
      P. oleovorans is encoded by a gene carried by plasmid pGEc47, which has been
      shown to effect facilitated uptake of oleic acid in E. coli W3110 (M. Nieboer,
      Ph.D. thesis, University of Groningen, Groningen, The Netherlands, 1996). By
      using a double recombinant of E. coli K27, which is a fadD mutant and therefore
      unable to consume substrates or products via the beta-oxidation cycle, a twofold
      increase in productivity was achieved. Applying cytochrome P-450BM-3
      monooxygenase as a biocatalyst in whole cells does not require the exogenous
      addition of the costly cofactor NADPH. In combination with the coenzyme A
      independent fatty acid uptake system from P. oleovorans, cytochrome P-450BM-3
      recombinants appear to be useful alternatives to the enzymatic approach for the
      bioconversion of long-chain fatty acids to subterminal hydroxylated fatty acids.

PMID- 9758802
TI  - Degradation of 1,2,3,4-tetrachlorobenzene by pseudomonas chlororaphis RW71 
AB  - Pseudomonas chlororaphis RW71 mineralized 1,2,3,4-tetrachlorobenzene, a highly
      recalcitrant pollutant hitherto not known to be degraded by pure cultures, as a
      sole source of carbon and energy, thereby releasing stoichiometric amounts of
      chloride. The transient excretion of tetrachlorocatechol in the early growth
      phase suggests an initial attack by a dioxygenase to form the corresponding
      dihydrodiol which rearomatizes to the catechol. The activity of chlorocatechol
      1,2-dioxygenase in crude cell extracts was found to be extraordinarily high
      towards 3-chlorocatechol (ratio of 2.6 compared to catechol) and other
      chlorocatechols, including tetrachlorocatechol, which was transformed at a low
      but significant rate. Further identification of tetrachloromuconic acid, 2,3, 5
      trichlorodienelactone, 2,3,5-trichloromaleyl acetic acid, and 2, 4-dichloro-3
      oxoadipic acid as their methyl esters, together with high specific enzyme
      activities for chlorinated substrates, implicated a functioning chlorocatechol
      pathway to be induced during growth.

PMID- 9758804
TI  - Quantitative and physiological analyses of chloride dependence of growth of
      halobacillus halophilus 
AB  - A quantitative analysis of the Cl- dependence of growth of Halobacillus
      halophilus was performed. Optimal growth rates were obtained at Cl-
      concentrations of between 0.5 and 2.0 M, and the final yield was also strictly
      dependent on the Cl- concentration. Br- but not I-, SO42-, NO2-, SO2-, OCN-, SCN
      , BO2-, or BrO3- could substitute for Cl-. To analyze the function of chloride,
      chloride concentration was determined. At low external Cl- (Cle-) concentrations,
      the growth rate was low and Cl- was excluded from the cytoplasm; increasing the
      Cle- concentration led to an increase in the growth rate and an energy-dependent
      uptake of Cl-, thus decreasing the Cle-/internal Cli- gradient from >/=10 at 0.1
      M Cle- to a nearly constant value of 2 at Cle- concentrations which allowed
      optimal growth. Two membrane proteins with apparent molecular masses of 31 and 16
      kDa which were identified to be specific for Cl--grown cultures are possible
      candidates for a chloride uptake system.

PMID- 9758803
TI  - Characteristics of airborne actinomycete spores.
AB  - Airborne actinomycete spores, important contaminants in occupational and
      residential environments, were studied with respect to their (i) release into the
      air, (ii) aerodynamic and physical size while airborne, and (iii) survival after
      collection onto agar with an impactor. Three actinomycete species were selected
      for the tests to exemplify the three main spore types: Streptomyces albus for
      arthrospores, Micromonospora halophytica for aleuriospores, and Thermoactinomyces
      vulgaris for endospores. The results show that the incubation conditions
      (temperature, time, and nutrients) needed for the development of spores for their
      release into air are different from the conditions that are needed for colony
      growth only. Additional drying of M. halophytica and T. vulgaris cultures was
      needed before spores could be released from the culture. The aerodynamic sizes of
      the spores, measured with an aerodynamic particle sizer, ranged from 0.57 (T.
      vulgaris) to 1.28 micron (M. halophytica). The physical sizes of the spores, when
      measured with a microscope and an image analysis system, were found to be smaller
      than previously reported in the literature. The relative recovery of the spores
      on agar media ranged from 0.5 (T. vulgaris) to 35% (S. albus). The results
      indicate that the culturability of the collected airborne actinomycete spores
      varies widely and is affected by several variables, such as the species and the
      sampling flow rate. Therefore, alternatives to commonly used cultivation methods
      need to be developed for the enumeration of actinomycete spores.

PMID- 9758805
TI  - Genetic characterization of pseudomonas syringae pv. syringae strains from stone
      fruits in california 
AB  - Strains of Pseudomonas syringae pv. syringae were isolated from healthy and
      diseased stone fruit tissues sampled from 43 orchard sites in California in 1995
      and 1996. These strains, together with P. syringae strains from other hosts and
      pathovars, were tested for pathogenicity and the presence of the syrB and syrC
      genes and were genetically characterized by using enterobacterial repetitive
      intergenic consensus (ERIC) primers and PCR. All 89 strains of P. syringae pv.
      syringae tested were moderately to highly pathogenic on Lovell peach seedlings
      regardless of the host of origin, while strains of other pathovars exhibited low
      or no pathogenicity. The 19 strains of P. syringae pv. syringae examined by
      restriction fragment length polymorphism analysis contained the syrB and syrC
      genes, whereas no hybridization occurred with 4 strains of other P. syringae
      pathovars. The P. syringae pv. syringae strains from stone fruit, except for a
      strain from New Zealand, generated ERIC genomic fingerprints which shared four
      fragments of similar mobility. Of the P. syringae pv. syringae strains tested
      from other hosts, only strains from rose, kiwi, and pear generated genomic
      fingerprints that had the same four fragments as the stone fruit strains.
      Analysis of the ERIC fingerprints from P. syringae pv. syringae strains showed
      that the strains isolated from stone fruits formed a distinct cluster separate
      from most of the strains isolated from other hosts. These results provide
      evidence of host specialization within the diverse pathovar P. syringae pv.
      syringae.

PMID- 9758806
TI  - Phenotypic and phylogenetic characterization of ruminal tannin-tolerant bacteria.
AB  - The 16S rRNA sequences and selected phenotypic characteristics were determined
      for six recently isolated bacteria that can tolerate high levels of hydrolyzable
      and condensed tannins. Bacteria were isolated from the ruminal contents of
      animals in different geographic locations, including Sardinian sheep (Ovis
      aries), Honduran and Colombian goats (Capra hircus), white-tail deer (Odocoileus
      virginianus) from upstate New York, and Rocky Mountain elk (Cervus elaphus
      nelsoni) from Oregon. Nearly complete sequences of the small-subunit rRNA genes,
      which were obtained by PCR amplification, cloning, and sequencing, were used for
      phylogenetic characterization. Comparisons of the 16S rRNA of the six isolates
      showed that four of the isolates were members of the genus Streptococcus and were
      most closely related to ruminal strains of Streptococcus bovis and the recently
      described organism Streptococcus gallolyticus. One of the other isolates, a gram
      positive rod, clustered with the clostridia in the low-G+C-content group of gram
      positive bacteria. The sixth isolate, a gram-negative rod, was a member of the
      family Enterobacteriaceae in the gamma subdivision of the class Proteobacteria.
      None of the 16S rRNA sequences of the tannin-tolerant bacteria examined was
      identical to the sequence of any previously described microorganism or to the
      sequence of any of the other organisms examined in this study. Three
      phylogenetically distinct groups of ruminal bacteria were isolated from four
      species of ruminants in Europe, North America, and South America. The presence of
      tannin-tolerant bacteria is not restricted by climate, geography, or host animal,
      although attempts to isolate tannin-tolerant bacteria from cows on low-tannin
      diets failed.

PMID- 9758808
TI  - Enzymatic activity, bacterial distribution, and organic matter composition in
      sediments of the ross sea (Antarctica) 
AB  - Enzymatic activities of aminopeptidase and beta-glucosidase were investigated in
      Antarctic Ross Sea sediments at two sites (sites B and C, 567 and 439 m deep,
      respectively). The sites differed in trophic conditions related to organic matter
      (OM) composition and bacterial distribution. Carbohydrate concentrations at site
      B were about double those at site C, while protein and lipid levels were 10 times
      higher. Proteins were mainly found in a soluble fraction (>90%). Chloropigment
      content was generally low and phaeopigments were almost absent, indicating the
      presence of reduced inputs of primary organic matter. ATP concentrations (as a
      measure of the living microbial biomass) were significantly higher at site B. By
      contrast, benthic bacterial densities at site C were about double those at site
      B. Bacterial parameters do not appear to be "bottom-up controlled" by the amount
      of available food but rather "top-down controlled" by meiofauna predatory
      pressure, which was significantly higher at site B. Aminopeptidase and beta
      glucosidase extracellular enzyme activities (EEA) in Antarctic sediments appear
      to be high and comparable to those reported for temperate or Arctic sediments and
      characterized by low aminopeptidase/beta-glucosidase ratios (about 10). Activity
      profiles showed decreasing patterns with increasing sediment depth, indicating
      vertical shifts in both availability and nutritional quality of degradable OM.
      Vertical profiles of aminopeptidase activity were related to a decrease in
      protein concentration and/or to an increase in the insoluble refractory
      proteinaceous fraction. The highest aminopeptidase activity rates were observed
      at site C, characterized by much lower protein concentrations. Differences in EEA
      between sites do not seem to be explained by differences in the in situ
      temperature (-1.6 and -0.8 degreesC at sites B and C, respectively).
      Aminopeptidase activity profiles are consistent with the bacterial biomass and
      frequency of dividing cells. Enzyme substrate affinity was generally dependent
      upon substrate concentrations. EEA, normalized to bacterial numbers, indicated
      specific activities comparable to those reported for equally deep sediments at
      temperate latitudes. Vertical patterns of specific enzymatic activity appeared to
      be controlled by chloroplastic pigment concentrations that accumulate in the
      deeper sediment layers. The overall conclusion from the analysis of EEA in
      Antarctic sediments is that enzyme-dependent transformations of OM proceed at
      rates similar to those measured in temperate environments. Protein carbon
      potentially liberated by aminopeptidase activities (12.597 to 26.190 mg of C m-2
      day-1) indicates that the whole protein pool could be mobilized within 1.3 to 17
      h. Carbohydrate carbon mobilization (773 to 2,552 mg of C m-2 day-1) is
      sufficient to turn over the carbohydrate pool within 16 to 20 h. Such rates are 6
      to 45 times higher than fluxes of particulate organic proteins and carbohydrates,
      indicating an "uncoupled hydrolysis" by the Antarctic benthic assemblages, in
      which bacteria appear to be able to rapidly exploit episodic OM pulses.

PMID- 9758807
TI  - Improvement of nitrogen assimilation and fermentation kinetics under enological
      conditions by derepression of alternative nitrogen-assimilatory pathways in an
      industrial Saccharomyces cerevisiae strain.
AB  - Metabolism of nitrogen compounds by yeasts affects the efficiency of wine
      fermentation. Ammonium ions, normally present in grape musts, reduce catabolic
      enzyme levels and transport activities for nonpreferred nitrogen sources. This
      nitrogen catabolite repression severely impairs the utilization of proline and
      arginine, both common nitrogen sources in grape juice that require the proline
      utilization pathway for their assimilation. We attempted to improve fermentation
      performance by genetic alteration of the regulation of nitrogen-assimilatory
      pathways in Saccharomyces cerevisiae. One mutant carrying a recessive allele of
      ure2 was isolated from an industrial S. cerevisiae strain. This mutation strongly
      deregulated the proline utilization pathway. Fermentation kinetics of this mutant
      were studied under enological conditions on simulated standard grape juices with
      various nitrogen levels. Mutant strains produced more biomass and exhibited a
      higher maximum CO2 production rate than the wild type. These differences were
      primarily due to the derepression of amino acid utilization pathways. When low
      amounts of dissolved oxygen were added, the mutants could assimilate proline.
      Biomass yield and fermentation rate were consequently increased, and the duration
      of the fermentation was substantially shortened. S. cerevisiae strains lacking
      URE2 function could improve alcoholic fermentation of natural media where proline
      and other poorly assimilated amino acids are the major potential nitrogen source,
      as is the case for most fruit juices and grape musts.

PMID- 9758809
TI  - Interlaboratory comparison of methods To quantify microsclerotia of verticillium
      dahliae in soil 
AB  - In a comparison of different methods for estimating Verticillium dahliae in soil,
      14 soil samples were analyzed in a blinded fashion by 13 research groups in seven
      countries, using their preferred methods. One group analyzed only four samples.
      Twelve soil samples were naturally infested, and two had known numbers of
      microsclerotia of V. dahliae added to them. In addition, a control was included
      to determine whether transport had an effect on the results. Results differed
      considerably among the research groups. There was a 118-fold difference between
      the groups with the lowest and highest mean estimates. Results of the other
      groups were evenly distributed between these extremes. In general, methods based
      on plating dry soil samples gave higher numbers of V. dahliae than did plating of
      an aqueous soil suspension. Recovery of V. dahliae from samples with added
      microsclerotia varied from 0 to 59%. Most of the variability within each analysis
      was at the petri dish level. The results indicate the necessity to check the
      performance of detection assays regularly by comparing recoveries with other
      laboratories, using a common set of soil samples. We conclude that wet plating
      assays are less accurate than dry plating assays.

PMID- 9758810
TI  - Temperature gradient gel electrophoresis analysis of 16S rRNA from human fecal
      samples reveals stable and host-specific communities of active bacteria.
AB  - The diversity of the predominant bacteria in the human gastrointestinal tract was
      studied by using 16S rRNA-based approaches. PCR amplicons of the V6 to V8 regions
      of fecal 16S rRNA and ribosomal DNA (rDNA) were analyzed by temperature gradient
      gel electrophoresis (TGGE). TGGE of fecal 16S rDNA amplicons from 16 individuals
      showed different profiles, with some bands in common. Fecal samples from two
      individuals were monitored over time and showed remarkably stable profiles over a
      period of at least 6 months. TGGE profiles derived from 16S rRNA and rDNA
      amplicons showed similar banding patterns. However, the intensities of bands with
      similar mobilities differed in some cases, indicating a different contribution to
      the total active fraction of the prominent fecal bacteria. Most 16S rRNA
      amplicons in the TGGE pattern of one subject were identified by cloning and
      sequence analysis. Forty-five of the 78 clones matched 15 bands, and 33 clones
      did not match any visible band in the TGGE pattern. Nested PCR of amplified 16S
      rDNA indicated preferential amplification of a sequence corresponding to 12 of
      the 33 nonmatching clones with similar mobilities in TGGE. The sequences matching
      15 bands in the TGGE pattern showed 91.5 to 98.7% homology to sequences derived
      from different Clostridium clusters. Most of these were related to strains
      derived from the human intestine. The results indicate that the combination of
      cloning and TGGE analysis of 16S rDNA amplicons is a reliable approach to
      monitoring different microbial communities in feces.

PMID- 9758811
TI  - Comparison of paenibacillus azotofixans strains isolated from rhizoplane,
      rhizosphere, and non-root-associated soil from maize planted in two different
      brazilian soils 
AB  - Paenibacillus azotofixans is a nitrogen-fixing bacterium often found in soil and
      in the rhizospheres of different grasses. In this study, two Brazilian clay soils
      were planted with cross-hybrid maize (BR-201) and four stages of plant growth
      were analyzed to characterize the P. azotofixans populations present in the
      rhizoplanes, rhizospheres, and non-root-associated soils (herein called
      nonrhizospheres). A total of 106 strains were isolated and identified as P.
      azotofixans with an API 50CH kit, by classical biochemical tests, and via the use
      of specific primers based on the 16S rRNA gene in PCRs. To compare the isolated
      strains, phenotypic characteristics were determined and three different probes
      were used in hybridization experiments: two nif probes and one probe comprising a
      0.58-kb fragment cloned from the P. azotofixans C3L4 genome. These results were
      used to construct a dendrogram, in which two main clusters could be observed. One
      cluster contained exclusively strains from Varzea soil, and the other contained
      the majority of strains from Cerrado soil. The 60 strains from Varzea soil and
      the 46 strains from Cerrado soil were further analyzed with REP and BOX primers,
      respectively. Based on the patterns obtained, it was possible to identify 21
      different groups among strains from Varzea soil and 4 different groups among
      strains from Cerrado soil. These different patterns were tested by multivariate
      analysis of variance, and differences in the populations of P. azotofixans during
      the four stages of plant growth were demonstrated. Moreover, strains isolated
      from the rhizoplanes, rhizospheres, and nonrhizospheres of maize planted in
      Cerrado and Varzea soils were shown to be statistically different; the diversity
      of P. azotofixans strains was affected by the soil type.

PMID- 9758812
TI  - Microbial diversity in a hydrocarbon- and chlorinated-solvent-contaminated
      aquifer undergoing intrinsic bioremediation.
AB  - A culture-independent molecular phylogenetic approach was used to survey
      constituents of microbial communities associated with an aquifer contaminated
      with hydrocarbons (mainly jet fuel) and chlorinated solvents undergoing intrinsic
      bioremediation. Samples were obtained from three redox zones: methanogenic,
      methanogenic-sulfate reducing, and iron or sulfate reducing. Small-subunit rRNA
      genes were amplified directly from aquifer material DNA by PCR with universally
      conserved or Bacteria- or Archaea-specific primers and were cloned. A total of
      812 clones were screened by restriction fragment length polymorphisms (RFLP),
      approximately 50% of which were unique. All RFLP types that occurred more than
      once in the libraries, as well as many of the unique types, were sequenced. A
      total of 104 (94 bacterial and 10 archaeal) sequence types were determined. Of
      the 94 bacterial sequence types, 10 have no phylogenetic association with known
      taxonomic divisions and are phylogenetically grouped in six novel division level
      groups (candidate divisions WS1 to WS6); 21 belong to four recently described
      candidate divisions with no cultivated representatives (OP5, OP8, OP10, and
      OP11); and 63 are phylogenetically associated with 10 well-recognized divisions.
      The physiology of two particularly abundant sequence types obtained from the
      methanogenic zone could be inferred from their phylogenetic association with
      groups of microorganisms with a consistent phenotype. One of these sequence types
      is associated with the genus Syntrophus; Syntrophus spp. produce energy from the
      anaerobic oxidation of organic acids, with the production of acetate and
      hydrogen. The organism represented by the other sequence type is closely related
      to Methanosaeta spp., which are known to be capable of energy generation only
      through aceticlastic methanogenesis. We hypothesize, therefore, that the terminal
      step of hydrocarbon degradation in the methanogenic zone of the aquifer is
      aceticlastic methanogenesis and that the microorganisms represented by these two
      sequence types occur in syntrophic association.

PMID- 9758813
TI  - Stereo- and regioselective hydroxylation of alpha-ionone by Streptomyces strains.
AB  - A total of 215 Streptomyces strains were screened for their capacity to regio-
      and stereoselectively hydroxylate beta- and/or alpha-ionone to the respective 3
      hydroxy derivatives. With beta-ionone as the substrate, 15 strains showed little
      conversion to 4-hydroxy- and none showed conversion to the 3-hydroxy product as
      desired. Among these 15 Streptomyces strains, S. fradiae Tu 27, S. arenae Tu 495,
      S. griseus ATCC 13273, S. violaceoniger Tu 38, and S. antibioticus Tu 4 and Tu 46
      converted alpha-ionone to 3-hydroxy-alpha-ionone with significantly higher
      hydroxylation activity compared to that of beta-ionone. Hydroxylation of racemic
      alpha-ionone [(6R)-(-)/(6S)-(+)] resulted in the exclusive formation of only the
      two enantiomers (3R,6R)- and (3S, 6S)-hydroxy-alpha-ionone. Thus, the enzymatic
      hydroxylation of alpha-ionone by the Streptomyces strains tested proceeds with
      both high regio- and stereoselectivity.

PMID- 9758814
TI  - Acid-sensitive enteric pathogens are protected from killing under extremely
      acidic conditions of pH 2.5 when they are inoculated onto certain solid food
      sources.
AB  - Gastric acidity is recognized as the first line of defense against food-borne
      pathogens, and the ability of pathogens to resist this pH corresponds to their
      oral infective dose (ID). Naturally occurring and genetically engineered acid
      sensitive enteric pathogens were examined for their ability to survive under
      acidic conditions of pH 2.5 for 2 h at 37 degreesC when inoculated onto ground
      beef. Each of the strains displayed significantly high survival rates under these
      normally lethal conditions. The acid-sensitive pathogens Campylobacter jejuni and
      Vibrio cholerae, which were protected at lower levels from acid-induced killing
      by ground beef under these conditions, were sensitive to killing in acidified
      media at pH 5.0 but survived at pH 6.0. Salmonella inoculated onto the surface of
      preacidified ground beef could not survive if the pH on the surface of the beef
      was 2.61 or lower but was viable if the surface pH was 3. 27. This implies that
      the pH of the microenvironment occupied by the bacteria on the surface of the
      food source is critical for their survival. Salmonella was also shown to be
      protected from killing when inoculated onto boiled egg white, a food source high
      in protein and low in fat. These results may explain why Salmonella species have
      a higher oral ID of approximately 10(5) cells when administered under defined
      conditions but have been observed to cause disease at doses as low as 50 to 100
      organisms when consumed as part of a contaminated food source. They may also help
      explain why some pathogens are associated primarily with food-borne modes of
      transmission rather than fecal-oral transmission.

PMID- 9758815
TI  - New hybrids between Saccharomyces sensu stricto yeast species found among wine
      and cider production strains.
AB  - Two yeast isolates, a wine-making yeast first identified as a Mel+ strain (ex. S.
      uvarum) and a cider-making yeast, were characterized for their nuclear and
      mitochondrial genomes. Electrophoretic karyotyping analyses, restriction fragment
      length polymorphism maps of PCR-amplified MET2 gene fragments, and the sequence
      analysis of a part of the two MET2 gene alleles found support the notion that
      these two strains constitute hybrids between Saccharomyces cerevisiae and
      Saccharomyces bayanus. The two hybrid strains had completely different
      restriction patterns of mitochondrial DNA as well as different sequences of the
      OLI1 gene. The sequence of the OLI1 gene from the wine hybrid strain appeared to
      be the same as that of the S. cerevisiae gene, whereas the OLI1 gene of the cider
      hybrid strain is equally divergent from both putative parents, S. bayanus and S.
      cerevisiae. Some fermentative properties were also examined, and one phenotype
      was found to reflect the hybrid nature of these two strains. The origin and
      nature of such hybridization events are discussed.

PMID- 9758816
TI  - Effects of visible light and UV radiation on photosynthesis in a population of a
      hot spring cyanobacterium, a synechococcus sp., subjected to high-temperature
      stress 
AB  - Assays of photosynthesis were conducted with a biofilm population of a
      cyanobacterium, a Synechococcus sp., growing at approximately 70 degreesC in a
      Yellowstone National Park hot spring to test whether cells growing near the upper
      temperature limit of photosynthetic life are optimally adapted to their mean
      environmental temperature. Cell suspensions were assayed at 70, 65, and 55
      degreesC while being simultaneously exposed to modified solar environments,
      including reduction of total irradiance and exclusion of UV radiation. Carbon
      fixation was greatest at 65 degreesC, while 70 and 55 degreesC were always
      supraoptimal and suboptimal for photosynthesis, respectively. The degree of
      temperature stress was dependent upon light intensity, and this light-dependent
      temperature effect may involve both reduced quantum efficiency at subsaturating
      irradiances and a lower saturating irradiance at both supraoptimal and suboptimal
      temperatures. The Synechococcus sp. was also more susceptible to UV inhibition of
      photosynthesis at nonoptimal temperatures. These results suggest that this
      population is persisting at a nearly lethal temperature and is consequently
      subject to greater damage by both visible and UV radiation, but it is speculated
      that these cells may be avoiding competition with other photoautotrophs under
      these nonoptimal conditions. In separate experiments monitoring diurnal patterns
      of photosynthesis, cells exhibited peak productivity during the morning, followed
      by an afternoon decline. No recovery of photosynthesis was observed during the
      remaining daytime, and carbon fixation was always UV inhibited under conditions
      of photosynthetically saturating light.

PMID- 9758817
TI  - Determination of the biomasses of small bacteria at low concentrations in a
      mixture of species with forward light scatter measurements by flow cytometry 
AB  - The forward light scatter intensity of bacteria analyzed by flow cytometry varied
      with their dry mass, in accordance with theory. A standard curve was formulated
      with Rayleigh-Gans theory to accommodate cell shape and alignment. It was
      calibrated with an extinction-culture isolate of the small marine organism
      Cycloclasticus oligotrophus, for which dry weight was determined by CHN analysis
      and 14C-acetate incorporation. Increased light scatter intensity due to
      formaldehyde accumulation in preserved cells was included in the standard curve.
      When differences in the refractive indices of culture media and interspecies
      differences in the effects of preservation were taken into account, there was
      agreement between cell mass obtained by flow cytometry for various bacterial
      species and cell mass computed from Coulter Counter volume and buoyant density.
      This agreement validated the standard curve and supported the assumption that
      cells were aligned in the flow stream. Several subpopulations were resolved in a
      mixture of three species analyzed according to forward light scatter and DNA
      bound DAPI (4', 6-diamidino-2-phenylindole) fluorescence intensity. The total
      biomass of the mixture was 340 &mgr;g/liter. The lowest value for mean dry mass,
      0.027 +/- 0.008 pg/cell, was for the subpopulation of C. oligotrophus containing
      cells with a single chromosome. Calculations from measurements of dry mass,
      Coulter Counter volume, and buoyant density revealed that the dry weight of the
      isolate was 14 to 18% of its wet weight, compared to 30% for Escherichia coli.
      The method is suitable for cells with 0.005 to about 1.2 pg of dry weight at
      concentrations of as low as 10(3) cells/ml and offers a unique capability for
      determining biomass distributions in mixed bacterial populations.

PMID- 9758818
TI  - The introduction into bacillus sphaericus of the Bacillus thuringiensis subsp.
      medellin Cyt1Ab1 gene results in higher susceptibility of resistant mosquito
      larva populations to B. sphaericus.
AB  - The fragment containing the gene encoding the cytolytic Cyt1Ab1 protein from
      Bacillus thuringiensis subsp. medellin and its flanking sequences (I. Thiery, A.
      Delecluse, M. C. Tamayo, and S. Orduz, Appl. Environ. Microbiol. 63:468-473,
      1997) was introduced into Bacillus sphaericus toxic strains 2362, 2297, and
      Iab872 by electroporation with the shuttle vector pMK3. Only small amounts of the
      protein were produced in recombinant strains 2362 and Iab872. The protein was
      detected in these strains only by Western blotting and immunodetection with
      antibody raised against Cyt1Ab1 protein. Large amounts of Cyt1Ab1 protein were
      produced in B. sphaericus recombinant strain 2297, and there was an additional
      crystal, other than that of the binary toxin, within the exosporium. The
      production of the Cyt1Ab1 protein in addition to the binary toxin did not
      increase the larvicidal activity of the B. sphaericus recombinant strain against
      susceptible mosquito populations of Culex pipiens or Aedes aegypti. However, it
      partially restored (10 to 20 times) susceptibility of the resistant mosquito
      populations of C. pipiens (SPHAE) and Culex quinquefasciatus (GeoR) to the binary
      toxin. The Cyt1Ab1 protein produced in recombinant B. thuringiensis
      SPL407(pcyt1Ab1) was synthesized in two types of crystal-one round and with
      various dense areas, surrounded by an envelope, and the other a regular cuboid
      crystal, very similar to that found in the B. sphaericus recombinant strain.

PMID- 9758820
TI  - Occurrence of fusaproliferin and beauvericin in Fusarium-contaminated livestock
      feed in Iowa.
AB  - Fusarium fungal contaminants and related mycotoxins were investigated in eight
      maize feed samples submitted to the Iowa State University Veterinary Diagnostic
      Laboratory. Fusarium moniliforme, F. proliferatum, and F. subglutinans were
      isolated from seven, eight, and five samples, respectively. These strains
      belonged to mating populations A, D, and E of the teleomorph Gibberella
      fujikuroi. Fusaproliferin was detected at concentrations of 0.1 to 30 microg/g in
      four samples, and beauvericin was detected (0.1 to 3.0 microg/g) in five samples.
      Fumonisins were detected in all eight samples (1.1 to 14 microg/g). Ten of 11
      strains of F. proliferatum and all 12 strains of F. subglutinans isolated from
      the samples produced fusaproliferin in culture on whole maize kernels (4 to 350
      and 100 to 1,000 microg/g, respectively). Nine F. proliferatum strains also
      produced beauvericin in culture (85 to 350 microg/g), but none of the F.
      subglutinans strains produced beauvericin. Fumonisin B1 was produced by all nine
      F. moniliforme strains (50 to 2,000 microg/g) and by 10 of the F. proliferatum
      strains (1,000 to 2,000 microg/g). This is the first report of the natural
      occurrence of fusaproliferin outside Italy and of the natural occurrence of
      beauvericin in North America.

PMID- 9758819
TI  - Physiological activity of Campylobacter jejuni far below the minimal growth
      temperature.
AB  - The behavior of Campylobacter jejuni at environmental temperatures was examined
      by determining the physiological activities of this human pathogen. The minimal
      growth temperatures were found to be 32 and 31 degrees C for strains 104 and ATCC
      33560, respectively. Both strains exhibited a sudden decrease in growth rate from
      the maximum to zero within a few degrees not only near the maximal growth
      temperature but also near the minimal growth temperature. This could be an
      indication that a temperature-dependent transition in the structure of a key
      enzyme(s) or regulatory compound(s) determines the minimal growth temperature.
      Oxygen consumption, catalase activity, ATP generation, and protein synthesis were
      observed at temperatures as low as 4 degrees C, indicating that vital cellular
      processes were still functioning. PCR analysis showed that cold shock protein
      genes, which play a role in low-temperature adaptation in many bacteria, are not
      present in C. jejuni. The fact that chemotaxis and aerotaxis could be observed at
      all temperatures shows that the pathogen is able to move to favorable places at
      environmental temperatures, which may have significant implications for the
      survival of C. jejuni in the environment.

PMID- 9758821
TI  - Bacterial stress responses to 1-megahertz pulsed ultrasound in the presence of
      microbubbles.
AB  - Members of a panel of stress-responsive biosensors have been used to study the
      effect of megahertz frequency ultrasound on Escherichia coli. Insonification
      causes acoustic cavitation, the collapse of oscillating microbubbles in solution,
      which can damage bacterial cells. A focused 1-MHz ultrasound transducer, capable
      of generating a spatial peak pulse average intensity of 500 W/cm2, was used to
      treat liquid bacterial cultures. Stress-responsive promoters fused to luxCDABE
      allowed the continuous measurement of light produced as a result of protein
      damage, DNA damage, oxidative stress, and membrane perturbation. A promoter
      responsive to ammonia limitation was not transcriptionally activated under test
      conditions. In contrast to bacteria in exponentially growing cultures, those in
      stationary-phase cultures were more resistant to the effects of ultrasound
      treatment. Quantification of the degree of acoustic cavitation due to symmetric
      bubble collapse was measured by a 20-MHz passive transducer, the output of which
      appears to be only partially correlated with cellular damage and survival. The
      methods and results summarized here provide the basis for further investigation
      into applications, including the purification of water samples.

PMID- 9758822
TI  - Optimization of Cry3A yields in Bacillus thuringiensis by use of sporulation
      dependent promoters in combination with the STAB-SD mRNA sequence.
AB  - The insecticidal activity of Bacillus thuringiensis strains toxic to coleopterous
      insects is due to Cry3 proteins assembled into small rectangular crystals. Toxin
      synthesis in these strains is dependent primarily upon a promoter that is active
      in the stationary phase and a STAB-SD sequence that stabilizes the cry3
      transcript-ribosome complex. Here we show that significantly higher yields of
      Cry3A can be obtained by using dual sporulation-dependent cyt1Aa promoters to
      drive the expression of cry3Aa when the STAB-SD sequence is included in the
      construct. The Cry3A yield per unit of culture medium obtained with this
      expression system was 12.7-fold greater than that produced by DSM 2803, the wild
      type strain of B. thuringiensis from which Cry3Aa was originally described, and
      1.4-fold greater than that produced by NB176, a mutant of the same strain
      containing two or three copies of cry3Aa, which is the active ingredient of the
      commercial product Novodor, used for control of beetle pests. The toxicities of
      Cry3A produced with this construct or the wild-type strain were similar when
      assayed against larvae of the cottonwood leaf beetle, Chrysomela scripta. The
      volume of Cry3A crystals produced with cyt1Aa promoters and the STAB-SD sequence
      was 1.3-fold that of typical bipyramidal Cry1 crystals toxic to lepidopterous
      insects. The dual-promoter/STAB-SD system offers an additional method for
      potentially improving the efficacy of insecticides based on B. thuringiensis.

PMID- 9758824
TI  - Closely related plasmid replicons coexisting in the phytopathogen pseudomonas
      syringae show a mosaic organization of the replication region and altered
      incompatibility behavior 
AB  - Many Pseudomonas syringae strains contain native plasmids that are important for
      host-pathogen interactions, and most of them contain several coexisting plasmids
      (pPT23A-like plasmids) that cross-hybridize to replication sequences from pPT23A,
      which also carries a gene cluster coding for the phytotoxin coronatine in P.
      syringae pv. tomato PT23. In this study, three functional pPT23A-like replicons
      were cloned from P. syringae pv. glycinea race 6, suggesting that the
      compatibility of highly related replicons is a common feature of P. syringae
      strains. Hybridization experiments using three separate incompatibility
      determinants previously identified from pPT23A and the rulAB (UV radiation
      tolerance) genes showed that the organization of the replication region among
      pPT23A-like plasmids from several P. syringae pathovars is poorly conserved. The
      putative repA gene from four pPT23A-like replicons from P. syringae pv. glycinea
      race 6 was amplified by using specific primers. The restriction profiles of the
      resulting PCR products for the race 6 plasmids were more similar to each other
      than they were to that of pPT23A. These data, together with the existence of
      other cross-hybridizing DNA regions around the replicon among the race 6 pPT23A
      like plasmids, suggest that some of these plasmids may have originated from
      duplication events. Our results also imply that modifications of the repA
      sequences and the poor conservation of putative maintenance determinants
      contribute to the suppression of incompatibility among members of the pPT23A-like
      family, thus enhancing the genomic plasticity of P. syringae.

PMID- 9758825
TI  - A new genetic locus in sinorhizobium meliloti is involved in stachydrine
      utilization 
AB  - Stachydrine, a betaine released by germinating alfalfa seeds, functions as an
      inducer of nodulation genes, a catabolite, and an osmoprotectant in Sinorhizobium
      meliloti. Two stachydrine-inducible genes were found in S. meliloti 1021 by
      mutation with a Tn5-luxAB promoter probe. Both mutant strains (S10 and S11)
      formed effective alfalfa root nodules, but neither grew on stachydrine as the
      sole carbon and nitrogen source. When grown in the absence or presence of salt
      stress, S10 and S11 took up [14C]stachydrine as well as wild-type cells did, but
      neither used stachydrine effectively as an osmoprotectant. In the absence of salt
      stress, both S10 and S11 took up less [14C]proline than wild-type cells did. S10
      and S11 appeared to colonize alfalfa roots normally in single-strain tests, but
      when mixed with the wild-type strain, their rhizosphere counts were reduced more
      than 50% (P </= 0.01) relative to the wild type. These results suggest that
      stachydrine catabolism contributes to root colonization. DNA sequence analysis
      identified the mutated locus in S11 as putA, and the luxAB fusion in that gene
      was induced by proline as well as stachydrine. DNA that restored the capacity of
      mutant S10 to catabolize stachydrine contained a new open reading frame, stcD.
      All data are consistent with the concept that stcD codes for an enzyme that
      produces proline by demethylation of N-methylproline, a degradation product of
      stachydrine.

PMID- 9758823
TI  - Characterization of genes involved in biosynthesis of a novel antibiotic from
      Burkholderia cepacia BC11 and their role in biological control of Rhizoctonia
      solani.
AB  - Genetic manipulation of fluorescent pseudomonads has provided major insight into
      their production of antifungal molecules and their role in biological control of
      plant disease. Burkholderia cepacia also produces antifungal activities, but its
      biological control activity is much less well characterized, in part due to
      difficulties in applying genetic tools. Here we report genetic and biochemical
      characterization of a soil isolate of B. cepacia relating to its production of an
      unusual antibiotic that is very active against a variety of soil fungi.
      Purification and preliminary structural analyses suggest that this antibiotic
      (called AFC-BC11) is a novel lipopeptide associated largely with the cell
      membrane. Analysis of conditions for optimal production of AFC-BC11 indicated
      stringent environmental regulation of its synthesis. Furthermore, we show that
      production of AFC-BC11 is largely responsible for the ability of B. cepacia BC11
      to effectively control the damping-off of cotton caused by the fungal pathogen
      Rhizoctonia solani in a gnotobiotic system. Using Tn5 mutagenesis, we identified,
      cloned, and characterized a region of the genome of strain BC11 that is required
      for production of this antifungal metabolite. DNA sequence analysis suggested
      that this region encodes proteins directly involved in the production of a
      nonribosomally synthesized lipopeptide.

PMID- 9758826
TI  - Relatedness of strains of xanthomonas fragariae by restriction fragment length
      polymorphism, DNA-DNA reassociation, and fatty acid analyses 
AB  - The levels of relatedness of strains of Xanthomonas fragariae collected over
      several years from locations in Canada and the United States were compared by
      determining fatty acid methyl ester profiles, restriction fragment length
      polymorphisms (RFLP) based on pulsed-field gel electrophoresis (PFGE) analysis,
      and DNA-DNA reassociation values. Based on qualitative and quantitative
      differences in fatty acid profiles, the strains were divided into nine groups and
      four groups by the MIDI "10% rule" and unweighted pair analysis, respectively.
      Restriction analysis of genomic DNA by PFGE with two endonucleases (XbaI and
      SpeI) revealed four distinct profiles. When a third endonuclease (VspI) was used,
      one group was divided into three subgroups. The profile of the American Type
      Culture Collection type strain differed from the profile of every other strain of
      X. fragariae. Considerable diversity was observed within X. fragariae, although
      the majority of the strains represented a clonal population. The four groups
      based on fatty acid profiles were similar to the four groups based on RFLP, but
      neither method related groups to the geographic origins of the strains. The DNA
      DNA reassociation values were high for representative strains, providing evidence
      that all of the strains belong to the same species.

PMID- 9758827
TI  - PCR-Based detection of the causal agent of watermark disease in willows (Salix
      spp.) 
AB  - The watermark disease, caused by Brenneria salicis (formerly Erwinia salicis), is
      of significant concern wherever tree-forming willows are grown or occur
      naturally. The movement of infected, asymptomatic cuttings is a major cause of
      pathogen dispersal. A reliable and sensitive diagnostic procedure is necessary
      for the safe movement of willow planting material. We derived primers from the
      nucleotide sequence of the 16S rRNA gene of B. salicis for the development of a
      PCR to detect this pathogen. One set of primers, Es1a-Es4b, directed the
      amplification of a 553-bp fragment from B. salicis genomic DNA as well as B.
      salicis cells. PCR products were not observed when genomic DNA was tested for 27
      strains of other, related plant-associated bacteria. Genomic fingerprinting by
      amplification fragment length polymorphism of B. salicis strains, originating
      from four different countries, and related Brenneria, Pectobacterium, and Erwinia
      strains revealed a very high similarity among the B. salicis genomes, indicating
      that the spread of the pathogen is mainly due to the transportation of infected
      cuttings. The PCR had to be preceded by a DNA extraction in order to detect the
      pathogen in the vascular fluid of willows. The minimum number of cells that could
      be detected from vascular fluid was 20 CFU/ml. The PCR assays proved to be very
      sensitive and reliable in detecting B. salicis in willow plant material.

PMID- 9758828
TI  - Enzymatic conversion of glucose to UDP-4-keto-6-deoxyglucose in Streptomyces spp.
AB  - All of the 2,6-dideoxy sugars contained within the structure of chromomycin A3
      are derived from D-glucose. Enzyme assays were used to confirm the presence of
      hexokinase, phosphoglucomutase, UDPG pyrophosphorylase (UDPGP), and UDPG
      oxidoreductase (UDPGO), all of which are involved in the pathway of glucose
      activation and conversion into 2,6-dideoxyhexoses during chromomycin
      biosynthesis. Levels of the four enzymes in Streptomyces spp. cell extracts were
      correlated with the production of chromomycins. The pathway of sugar activation
      in Streptomyces spp. involves glucose 6-phosphorylation by hexokinase,
      isomerization to G-1-P catalyzed by phosphoglucomutase, synthesis of UDPG
      catalyzed by UDPGP, and formation of UDP-4-keto-6-deoxyglucose by UDPGO.

PMID- 9758829
TI  - Construction of a range of derivatives of the biological control strain
      agrobacterium rhizogenes K84: a study of factors involved in biological control
      of crown gall disease 
AB  - The biological control strain Agrobacterium rhizogenes K84 is an effective agent
      in the control of Agrobacterium pathogens, the causative agents of crown gall
      disease. A number of factors are thought to play a role in the control process,
      including production of the specific agrocins 84 and 434, which differ in the
      spectra of pathogenic strains that they inhibit in vitro. A range of derivatives
      of strain K84 has been developed with every combination of the three resident
      plasmids, pAgK84, pAgK434, and pAtK84b, including a plasmid-free strain. These
      derivatives produced either both, one, or neither of the characterized agrocins
      84 and 434 and were isolated by plasmid curing, conjugation, and Tn5 transposon
      mutagenesis. The ability of the derivative strains to inhibit gall formation on
      almond roots was compared to that of the wild-type K84 parent. Treatment with the
      plasmid-free derivative did not result in a significant level of control of an A.
      rhizogenes pathogen based on numbers or dry weight of galls formed on injured
      almond roots. The presence of plasmid pAgK84, pAgK434, or pAtK84b significantly
      enhanced the biological control efficacy of K84 derivatives, and the highest
      level of control was observed with strains harboring two or more plasmids. The
      results observed with strains deficient in agrocin 434 production suggest that
      this product may play an important role in the biological control of A.
      rhizogenes pathogens. The involvement of plasmid pAgK84b in biological control
      has not previously been reported. This study supports the conclusion that
      multiple factors are involved in the success of strain K84 as a biological
      control agent.

PMID- 9758831
TI  - Molecular diversity of rhizobia occurring on native shrubby legumes in
      southeastern australia 
AB  - The structure of rhizobial communities nodulating native shrubby legumes in open
      eucalypt forest of southeastern Australia was investigated by a molecular
      approach. Twenty-one genomic species were characterized by small-subunit
      ribosomal DNA PCR-restriction fragment length polymorphism and phylogenetic
      analyses, among 745 rhizobial strains isolated from nodules sampled on 32
      different legume host species at 12 sites. Among these rhizobial genomic species,
      16 belonged to the Bradyrhizobium subgroup, 2 to the Rhizobium leguminosarum
      subgroup, and 3 to the Mesorhizobium subgroup. Only one genomic species
      corresponded to a known species (Rhizobium tropici). The distribution of the
      various genomic species was highly unbalanced among the 745 isolates, legume
      hosts, and sites. Bradyrhizobium species were by far the most abundant, and
      Rhizobium tropici dominated among the Rhizobium and Mesorhizobium isolates in the
      generally acid soils where nodules were collected. Although a statistically
      significant association occurred between the eight most common genomic species
      and the 32 hosts, there was sufficient overlap in distributions that no clear
      specificity between rhizobial genomic species and legume taxa was observed.
      However, for three legume species, some preference for particular genomic species
      was suggested. Similarly, no geographical partitioning was found.

PMID- 9758830
TI  - A novel ATP-binding cassette transporter involved in multidrug resistance in the
      phytopathogenic fungus Penicillium digitatum.
AB  - Demethylation inhibitor (DMI)-resistant strains of the plant pathogenic fungus
      Penicillium digitatum were shown to be simultaneously resistant to cycloheximide,
      4-nitroquinoline-N-oxide (4NQO), and acriflavine. A PMR1 (Penicillium multidrug
      resistance) gene encoding an ATP-binding cassette (ABC) transporter (P
      glycoprotein) was cloned from a genomic DNA library of a DMI-resistant strain
      (LC2) of Penicillium digitatum by heterologous hybridization with a DNA fragment
      containing an ABC-encoding region from Botrytis cinerea. Sequence analysis
      revealed significant amino acid homology to the primary structures of PMR1
      (protein encoded by the PMR1 gene) and ABC transporters of Saccharomyces
      cerevisiae (PDR5 and SNQ2), Schizosaccharomyces pombe (HBA2), Candida albicans
      (CDR1), and Aspergillus nidulans (AtrA and AtrB). Disruption of the PMR1 gene of
      P. digitatum DMI-resistant strain LC2 demonstrated that PMR1 was an important
      determinant of resistance to DMIs. The effective concentrations inhibiting radial
      growth by 50% (EC50s) and the MICs of fenarimol and bitertanol for the PMR1
      disruptants (Deltapmr1 mutants) were equivalent to those for DMI-sensitive
      strains. Northern blot analysis indicated that severalfold more PMR1 transcript
      accumulated in the DMI-resistant strains compared with those in DMI-sensitive
      strains in the absence of fungicide. In both DMI-resistant and -sensitive
      strains, transcription of PMR1 was strongly enhanced within 10 min after
      treatment with the DMI fungicide triflumizole. These results suggested that the
      toxicant efflux system comprised of PMR1 participates directly in the DMI
      resistance of the fungus.

PMID- 9758833
TI  - Polymorphisms in phytophthora infestans: four mitochondrial haplotypes are
      detected after PCR amplification of DNA from pure cultures or from host lesions 
AB  - Four pairs of primers were designed for PCR amplification of known polymorphic
      regions of the mitochondrial genome of Phytophthora infestans. Digestion of the
      amplified products with restriction enzymes allows identification of previously
      identified haplotypes. Product P2 cut with MspI uniquely identifies haplotypes Ib
      and IIa, while types Ia and IIb are differentiated by digestion of product P4
      with EcoRI. Digestion of products P1 and P3 gave results similar to that with
      digestion of P4, but amplification of these products was less robust. Thus, all
      four common haplotypes are identified by amplifying and digesting products P2 and
      P4. Identification of haplotypes was also possible from DNA extracted directly
      from small, late-blight lesions on both tomato and potato leaves, making
      isolation of the fungus unnecessary. A rapid and efficient method of monitoring
      changes in the pathogen population is facilitated. These PCR primers were also
      useful for differentiating other Phytophthora species.

PMID- 9758834
TI  - A new operation for producing disease-suppressive compost from grass clippings 
AB  - This study evaluated the use of grass clippings discharged from golf courses as
      the raw material for production of a suppressive compost to control Rhizoctonia
      large-patch disease in mascarene grass. Bacillus subtilis N4, a mesophilic
      bacterium with suppressive effects on the pathogenic fungus Rhizoctonia solani
      AG2-2, was used as an inoculum in a procedure developed with the aim of
      controlling composting temperatures and inoculation timing. The population
      density of mesophilic bacteria in the raw material was reduced to around 5 log10
      CFU/g (dry weight) of composting material in the self-heating reaction at the
      initial stage of composting by maintaining a temperature of 80 degreesC for 1
      day. The inoculum was applied immediately, and the composting material was
      maintained at 40 degreesC for 3 days. This served both to highly concentrate the
      suppressive bacterium and to achieve sporulation. The temperature was then raised
      to 60 degreesC and maintained, enabling hygienic, high-speed composting while
      maintaining the population density of the suppressive bacterium as high as 8
      log10 CFU/g (dry weight) in the compost. The suppressiveness of compost made in
      this way was confirmed in a turf grass disease prevention assay.

PMID- 9758832
TI  - Isolation and identification of Helicobacter spp. from canine and feline gastric
      mucosa.
AB  - It is known that virtually all healthy adult dogs and cats harbor spiral
      helicobacters in their gastric mucosa. Three species, Helicobacter felis,
      Helicobacter bizzozeronii, and Helicobacter salomonis have been isolated in vitro
      from the gastric mucosa of these animals. The aims of this study were to evaluate
      the efficacy of an isolation method for canine and feline gastric helicobacters
      that has been developed at the University of Helsinki; to estimate the prevalence
      and distribution of these taxa in the samples examined; and to assess the
      efficacy and validity of an extensive set of standardized conventional phenotypic
      tests, whole-cell protein profiling, and ultrastructural analysis in identifying
      the different species isolated from canine and feline gastric mucosa. We cultured
      95 and 22 gastric mucosal biopsies from dogs and cats, respectively. Twenty-one
      H. bizzozeronii strains, 8 H. felis strains, 8 H. salomonis strains, 3 mixed
      cultures, 2 "Flexispira rappini"-like organisms, and 3 as yet uncharacterized
      strains were isolated from the dogs, and 3 H. felis strains were isolated from
      the cats. The methods used here yielded Helicobacter isolation rates of 51% from
      dogs and 13.6% from cats, which exceed those reported previously. The main
      difficulties were primary isolation, mixed cultures, and identification to the
      species level. In the species identification, a detailed morphological
      examination was found to yield important phenotypic characteristics. A large
      panel of biochemical and tolerance tests did not clearly differentiate the
      closely related species H. bizzozeronii, H. felis, and H. salomonis. Highly
      standardized whole-cell protein profiling was shown to be an excellent method for
      species identification. Improvements in culture conditions for these bacteria are
      still needed, especially for cats. A genetic identification method not requiring
      culture is needed for future studies of these very fastidious helicobacters, as
      the clinical significance and ecology of these species within the gastric mucosa
      of the domestic carnivores remain largely unknown.

PMID- 9758835
TI  - Purification and substrate specificities of two alpha-L-arabinofuranosidases from
      Aspergillus awamori IFO 4033.
AB  - alpha-L-Arabinofuranosidases I and II were purified from the culture filtrate of
      Aspergillus awamori IFO 4033 and had molecular weights of 81,000 and 62,000 and
      pIs of 3.3 and 3.6, respectively. Both enzymes had an optimum pH of 4.0 and an
      optimum temperature of 60 degreesC and exhibited stability at pH values from 3 to
      7 and at temperatures up to 60 degrees C. The enzymes released arabinose from p
      nitrophenyl-alpha-L-arabinofuranoside, O-alpha-L-arabinofuranosyl-(1-->3)-O-beta
      D-xylopyranosyl-(1-->4)-D-x ylopyranose, and arabinose-containing polysaccharides
      but not from O-beta-D-xylopyranosyl-(1-->2)-O-alpha-L-arabinofuranosyl-(1-->3)-O
      b eta-D-xylopyranosyl-(1-->4)-O-beta-D-xylopyranosyl-(1-->4)-D-xylopyra nose.
      alpha-L-Arabinofuranosidase I also released arabinose from O-beta-D-xylopy
      ranosyl-(1-->4)-[O-alpha-L-arabinofuranosyl- (1-->3)]- O-beta-D-xylopyranosyl-(1-
      >4)-D-xylopyranose. However, alpha-L-arabinofuranosidase II did not readily
      catalyze this hydrolysis reaction. alpha-L-Arabinofuranosidase I hydrolyzed all
      linkages that can occur between two alpha-L-arabinofuranosyl residues in the
      following order: (1-->5) linkage > (1-->3) linkage > (1-->2) linkage. alpha-L
      Arabinofuranosidase II hydrolyzed the linkages in the following order: (1-->5)
      linkage > (1-->2) linkage > (1-->3) linkage. alpha-L-Arabinofuranosidase I
      preferentially hydrolyzed the (1-->5) linkage of branched arabinotrisaccharide.
      On the other hand, alpha-L-arabinofuranosidase II preferentially hydrolyzed the
      (1-->3) linkage in the same substrate. alpha-L-Arabinofuranosidase I released
      arabinose from the nonreducing terminus of arabinan, whereas alpha-L
      arabinofuranosidase II preferentially hydrolyzed the arabinosyl side chain
      linkage of arabinan.

PMID- 9758836
TI  - Identification, characterization, and In situ detection of a fruit-body-specific
      hydrophobin of Pleurotus ostreatus.
AB  - Hydrophobins are small (length, about 100 +/- 25 amino acids), cysteine-rich,
      hydrophobic proteins that are present in large amounts in fungal cell walls,
      where they form part of the outermost layer (rodlet layer); sometimes, they can
      also be secreted into the medium. Different hydrophobins are associated with
      different developmental stages of a fungus, and their biological functions
      include protection of the hyphae against desiccation and attack by either
      bacterial or fungal parasites, hyphal adherence, and the lowering of surface
      tension of the culture medium to permit aerial growth of the hyphae. We
      identified and isolated a hydrophobin (fruit body hydrophobin 1 [Fbh1]) present
      in fruit bodies but absent in both monokaryotic and dikaryotic mycelia of the
      edible mushroom Pleurotus ostreatus. In order to study the temporal and spatial
      expression of the fbh1 gene, we determined the N-terminal amino acid sequence of
      Fbh1. We also synthesized and cloned the double-stranded cDNA corresponding to
      the full-length mRNA of Fbh1 to use it as a probe in both Northern blot and in
      situ hybridization experiments. Fbh1 mRNA is detectable in specific parts of the
      fruit body, and it is absent in other developmental stages.

PMID- 9758837
TI  - Spatial physiological heterogeneity in Pseudomonas aeruginosa biofilm is
      determined by oxygen availability.
AB  - The role of oxygen availability in determining the local physiological activity
      of Pseudomonas aeruginosa growing in biofilms was investigated. Biofilms grown in
      an ambient-air environment expressed approximately 1/15th the alkaline
      phosphatase specific activity of planktonic bacteria subjected to the same
      phosphate limitation treatment. Biofilms grown in a gaseous environment of pure
      oxygen exhibited 1.9 times the amount of alkaline phosphatase specific activity
      of air-grown biofilms, whereas biofilms grown in an environment in which the air
      was replaced with pure nitrogen prior to the inducing treatment did not develop
      alkaline phosphatase activity. Frozen cross sections of biofilms stained for
      alkaline phosphatase activity with a fluorogenic stain demonstrated that alkaline
      phosphatase activity was concentrated in distinct bands adjacent to the gaseous
      interfaces. These bands were approximately 30 micron thick with biofilms grown in
      air, 2 micron thick with biofilms grown in pure nitrogen, and 46 micron thick
      with biofilms grown in pure oxygen. Overall biofilm thickness ranged from
      approximately 117 to approximately 151 micron. Measurements with an oxygen
      microelectrode indicated that oxygen was depleted locally within the biofilm and
      that the oxygen-replete zone was of a dimension similar to that of the
      biologically active zone, as indicated by alkaline phosphatase induction. These
      experiments revealed marked spatial physiological heterogeneity within P.
      aeruginosa biofilms in which active protein synthesis was restricted by oxygen
      availability to the upper 30 micron of the biofilm. Such physiological
      heterogeneity has implications for microbial ecology and for understanding the
      reduced susceptibilities of biofilms to antimicrobial agents.

PMID- 9758838
TI  - Resistance to tellurite as a selection marker for genetic manipulations of
      Pseudomonas strains.
AB  - Resistance to the toxic compound potassium tellurite (Telr) has been employed as
      a selection marker built into a set of transposon vectors and broad-host-range
      plasmids tailored for genetic manipulations of Pseudomonas strains potentially
      destined for environmental release. In this study, the activated Telr
      determinants encoded by the cryptic telAB genes of plasmid RK2 were produced,
      along with the associated kilA gene, as DNA cassettes compatible with cognate
      vectors. In one case, the Telr determinants were assembled between the I and O
      ends of a suicide delivery vector for mini-Tn5 transposons. In another case, the
      kilA and telAB genes were combined with a minimal replicon derived from a variant
      of Pseudomonas plasmid pPS10, which is able to replicate in a variety of gram
      negative hosts and is endowed with a modular collection of cloning and expression
      assets. Either in the plasmid or in the transposon vector, the Telr marker was
      combined with a 12-kb DNA segment of plasmid pWW0 of Pseudomonas putida mt-2
      encoding the upper TOL pathway enzymes. This allowed construction of antibiotic
      resistance-free but selectable P. putida strains with the ability to grow on
      toluene as the sole carbon source through an ortho-cleavage catabolic pathway.

PMID- 9758840
TI  - A method for DNA extraction from the desert cyanobacterium chroococcidiopsis and
      its application to identification of ftsZ 
AB  - A method was developed for extraction of DNA from Chroococcidiopsis that
      overcomes obstacles posed by bacterial contamination and the presence of a thick
      envelope surrounding the cyanobacterial cells. The method is based on the
      resistance of Chroococcidiopsis to lysozyme and consists of a lysozyme treatment
      followed by osmotic shock that reduces the bacterial contamination by 3 orders of
      magnitude. Then DNase treatment is performed to eliminate DNA from the bacterial
      lysate. Lysis of Chroococcidiopsis cells is achieved by grinding with glass beads
      in the presence of hot phenol. Extracted DNA is further purified by cesium
      chloride density gradient ultracentrifugation. This method permitted the first
      molecular approach to the study of Chroococcidiopsis, and a 570-bp fragment of
      the gene ftsZ was cloned and sequenced.

PMID- 9758839
TI  - Specific cell wall proteins confer resistance to nisin upon yeast cells.
AB  - The cell wall of a yeast cell forms a barrier for various proteinaceous and
      nonproteinaceous molecules. Nisin, a small polypeptide and a well-known
      preservative active against gram-positive bacteria, was tested with wild-type
      Saccharomyces cerevisiae. This peptide had no effect on intact cells. However,
      removal of the cell wall facilitated access of nisin to the membrane and led to
      cell rupture. The roles of individual components of the cell wall in protection
      against nisin were studied by using synchronized cultures. Variation in nisin
      sensitivity was observed during the cell cycle. In the S phase, which is the
      phase in the cell cycle in which the permeability of the yeast wall to
      fluorescein isothiocyanate dextrans is highest, the cells were most sensitive to
      nisin. In contrast, the cells were most resistant to nisin after a peak in
      expression of the mRNA of cell wall protein 2 (Cwp2p), which coincided with the
      G2 phase of the cell cycle. A mutant lacking Cwp2p has been shown to be more
      sensitive to cell wall-interfering compounds and Zymolyase (J. M. Van der Vaart,
      L. H. Caro, J. W. Chapman, F. M. Klis, and C. T. Verrips, J. Bacteriol. 177:3104
      3110, 1995). Here we show that of the single cell wall protein knockouts, a Cwp2p
      deficient mutant is most sensitive to nisin. A mutant with a double knockout of
      Cwp1p and Cwp2p is hypersensitive to the peptide. Finally, in yeast mutants with
      impaired cell wall structure, expression of both CWP1 and CWP2 was modified. We
      concluded that Cwp2p plays a prominent role in protection of cells against
      antimicrobial peptides, such as nisin, and that Cwp1p and Cwp2p play a key role
      in the formation of a normal cell wall.

PMID- 9758841
TI  - Comparison of a new thiomicrospira strain from the mid-atlantic ridge with known
      hydrothermal vent isolates 
AB  - A new autotrophic Thiomicrospira strain, MA-3, was isolated from the surface of a
      polymetal sulfide deposit collected at a Mid-Atlantic Ridge hydrothermal vent
      site. The DNA homology among three vent isolates, Thiomicrospira crunogena,
      Thiomicrospira sp. strain L-12, and Thiomicrospira sp. strain MA-3, was 99.3% or
      higher, grouping them as the same species, T. crunogena (type strain, ATCC
      35932). The fact that T. crunogena and Thiomicrospira sp. strain L-12 were
      isolated from Pacific vent sites demonstrates a cosmopolitan distribution of this
      species.

PMID- 9758842
TI  - Activities of Bacillus thuringiensis insecticidal crystal proteins Cyt1Aa and
      Cyt2Aa against three species of sheep blowfly.
AB  - The toxicity of Bacillus thuringiensis Cyt1Aa protein to sheep blowfly larvae
      depends on its solubilization and proteolytic activation. Cyt1Aa crystals were
      not toxic. Full-length and trypsin-digested Cyt1Aa proteins were toxic to larvae
      of three species of sheep blowfly. Neither full-length nor trypsin-digested Cyt2A
      soluble crystal proteins were toxic.

PMID- 9758844
TI  - Possible transmission of Streptococcus iniae from wild fish to cultured marine
      fish.
AB  - Streptococcus iniae was isolated from diseased wild fish collected near a
      mariculture facility where gilthead sea bream and European sea bass exhibited a
      similar infection. Species-specific PCR and ribotyping confirmed that wild and
      cultured fish were infected by a single S. iniae clone. Wild fish are therefore
      potential amplifiers of pathogenic S. iniae strains.

PMID- 9758843
TI  - Use of phospholipid fatty acids and carbon source utilization patterns To track
      microbial community succession in developing compost.
AB  - Carbon source utilization and phospholipid fatty acid analyses were used to track
      the rapidly changing microbial community in composting dairy waste. Microbial
      abilities to utilize common plant sugars increased during composting. Community
      phospholipid profiles changed significantly over time. Phospholipids suggested
      the presence of more thermophiles and fewer bacteria with continued compost
      development.

PMID- 9758845
TI  - Development of bacterium-based heavy metal biosorbents: enhanced uptake of
      cadmium and mercury by Escherichia coli expressing a metal binding motif.
AB  - A gene coding for a de novo peptide sequence containing a metal binding motif was
      chemically synthesized and expressed in Escherichia coli as a fusion with the
      maltose binding protein. Bacterial cells expressing the metal binding peptide
      fusion demonstrated enhanced binding of Cd2+ and Hg2+ compared to bacterial cells
      lacking the metal binding peptide. The potential use of genetically engineered
      bacteria as biosorbents for the removal of heavy metals from wastewaters is
      discussed.

PMID- 9758846
TI  - Purification and characterization of an NAD-malic enzyme from Bradyrhizobium
      japonicum A1017.
AB  - An NAD-malic enzyme was purified to homogeneity from Bradyrhizobium japonicum
      A1017, and its molecular characteristics were surveyed. The enzyme exhibited
      native and subunit molecular masses of 388 and 85 kDa, respectively, suggesting
      that it exists as a homotetramer, and was activated by metabolic intermediates in
      glycolysis. The role of the enzyme in bacteroids' carbon metabolism is discussed.

PMID- 9758847
TI  - Balance of activities of alcohol acetyltransferase and esterase in Saccharomyces
      cerevisiae is important for production of isoamyl acetate.
AB  - Isoamyl acetate is synthesized from isoamyl alcohol and acetyl coenzyme A by
      alcohol acetyltransferase (AATFase) in Saccharomyces cerevisiae and is hydrolyzed
      by esterases at the same time. We hypothesized that the balance of both enzyme
      activities was important for optimum production of isoamyl acetate in sake
      brewing. To test this hypothesis, we constructed yeast strains with different
      numbers of copies of the AATFase gene (ATF1) and the isoamyl acetate-hydrolyzing
      esterase gene (IAH1) and used these strains in small-scale sake brewing.
      Fermentation profiles as well as components of the resulting sake were largely
      alike; however, the amount of isoamyl acetate in the sake increased with an
      increasing ratio of AATFase/Iah1p esterase activity. Therefore, we conclude that
      the balance of these two enzyme activities is important for isoamyl acetate
      accumulation in sake mash.

PMID- 9758848
TI  - A gliding bacterium strain inhibits adhesion and motility of another gliding
      bacterium strain in a marine biofilm 
AB  - Two species of gliding bacteria were isolated from a marine biofilm. They were
      described and identified as members of the genus Cytophaga. One of them (RB1057)
      produced an extracellular inhibitor of colony expansion of the other (RB1058).
      The inhibitor was characterized as a glycoprotein with an apparent molecular mass
      of 60 kDa. It inhibited RB1058 adhesion to and gliding on substrata. Motility and
      adhesion of several other aquatic gliding bacteria were not measurably affected
      by this agent.

PMID- 9758850
TI  - Evidence for interspecies gene transfer in the evolution of 2,4
      dichlorophenoxyacetic acid degraders.
AB  - Small-subunit ribosomal DNA (SSU rDNA) from 20 phenotypically distinct strains of
      2,4-dichlorophenoxyacetic acid (2,4-D)-degrading bacteria was partially
      sequenced, yielding 18 unique strains belonging to members of the alpha, beta,
      and gamma subgroups of the class Proteobacteria. To understand the origin of 2,4
      D degradation in this diverse collection, the first gene in the 2,4-D pathway,
      tfdA, was sequenced. The sequences fell into three unique classes found in
      various members of the beta and gamma subgroups of Proteobacteria. None of the
      alpha-Proteobacteria yielded tfdA PCR products. A comparison of the dendrogram of
      the tfdA genes with that of the SSU rDNA genes demonstrated incongruency in
      phylogenies, and hence 2,4-D degradation must have originated from gene transfer
      between species. Only those strains with tfdA sequences highly similar to the
      tfdA sequence of strain JMP134 (tfdA class I) transferred all the 2,4-D genes and
      conferred the 2,4-D degradation phenotype to a Burkholderia cepacia recipient.

PMID- 9758849
TI  - Effective recovery of bacterial DNA and percent-guanine-plus-cytosine-based
      analysis of community structure in the gastrointestinal tract of broiler
      chickens.
AB  - A DNA-based, direct method for initial characterization of the total bacterial
      community in ileum and cecum of the chicken gastrointestinal (GI) tract was
      developed. The efficiencies of bacterial extraction and lysis were >95 and >99%,
      respectively, and therefore the DNA recovered should accurately reflect the
      bacterial communities of the ileal and cecal digesta. Total bacterial DNA samples
      were fractionated according to their percent G+C content. The profiles reflecting
      the composition of the bacterial community were reproducible within each
      compartment, but different between the compartments of the GI tract. This
      approach is independent of the culturability of the bacteria in the consortium
      and can be used to improve our understanding of how diet and other variables
      modulate the microbial communities of the GI tracts of animals.

PMID- 9758852
TI  - Synthesis of glycine betaine from exogenous choline in the moderately halophilic
      bacterium halomonas elongata 
AB  - The role of choline in osmoprotection in the moderate halophile Halomonas
      elongata has been examined. Transport and conversion of choline to betaine began
      immediately after addition of choline to the growth medium. Intracellular
      accumulation of betaine synthesized from choline was salt dependent up to 2.5 M
      NaCl. Oxidation of choline was enhanced at 2.0 M NaCl in the presence or absence
      of externally provided betaine. This indicates that the NaCl concentration in the
      growth medium has major effects on the choline-betaine pathway of H. elongata.

PMID- 9758851
TI  - Substrate selectivity and biochemical properties of 4-hydroxy-2-keto-pentanoic
      acid aldolase from Escherichia coli.
AB  - 4-Hydroxy-2-keto-pentanoic acid aldolase from Escherichia coli was identified as
      a class I aldolase. The enzyme was found to be highly selective for the
      acetaldehyde acceptor but would accept alpha-ketobutyric acid or phenylpyruvic
      acid in place of the pyruvic acid carbonyl donor.

PMID- 9758853
TI  - Loss of ammonia monooxygenase activity in nitrosomonas europaea upon exposure to
      nitrite 
AB  - Nitrosomonas europaea, an obligate ammonia-oxidizing bacterium, lost an
      increasing amount of ammonia oxidation activity upon exposure to increasing
      concentrations of nitrite, the primary product of ammonia-oxidizing metabolism.
      The loss of activity was specific to the ammonia monooxygenase (AMO) enzyme, as
      confirmed by a decreased rate of NH4+-dependent O2 consumption, some loss of
      active AMO molecules observed by polypeptide labeling with 14C2H2, the protection
      of activity by substrates of AMO, and the requirement for copper. The loss of AMO
      activity via nitrite occurred under both aerobic and anaerobic conditions, and
      more activity was lost under alkaline than under acidic conditions except in the
      presence of large concentrations (20 mM) of nitrite. These results indicate that
      nitrite toxicity in N. europaea is mediated by a unique mechanism that is
      specific for AMO.

PMID- 9758854
TI  - Persistence of PCR-detectable Bacteroides distasonis from human feces in river
      water.
AB  - To evaluate the persistence of PCR-detectable Bacteroides distasonis in surface
      water, whole human feces were dispersed into water from the Ohio River and
      incubated in flasks in the laboratory or in diffusion chambers in situ. Duplicate
      samples were taken daily, and material that pelleted at 16,000 x g was assayed by
      PCR. Persistence of PCR-detectable DNA from this anaerobe depended upon
      temperature and predation, two of the factors shown by others to influence the
      survival of aerobic bacteria detected by culture. B. distasonis was detected by
      PCR for at least 2 weeks at 4 degrees C but for only 4 to 5 days at 14 degrees C,
      1 to 2 days at 24 degrees C, and 1 day at 30 degrees C. In filtered water or in
      the presence of cycloheximide, a eukaryotic inhibitor, persistence at 24 degrees
      C was extended by at least a week.

PMID- 9758855
TI  - Oxidation of morphine to 2,2'-bimorphine by cylindrocarpon didymum 
AB  - The oxidation of morphine by whole-cell suspensions and cell extracts of
      Cylindrocarpon didymum gave rise to the formation of 2, 2'-bimorphine. The
      identity of 2,2'-bimorphine was confirmed by mass spectrometry and 1H nuclear
      magnetic resonance spectroscopy. C. didymum also displayed activity with the
      morphine analogs hydromorphone, 6-acetylmorphine, and dihydromorphine, but not
      codeine or diamorphine, suggesting that a phenolic group at C-3 is essential for
      activity.

PMID- 9758856
TI  - Heat killing of Bacillus subtilis spores in water is not due to oxidative damage.
AB  - The heat resistance of wild-type spores of Bacillus subtilis or spores (termed
      alpha-beta-) lacking DNA protective alpha/beta-type small, acid-soluble spore
      proteins was not altered by anaerobiosis or high concentrations of the free
      radical scavenging agents ethanethiol and ethanedithiol. Heat-killed wild-type
      and alpha-beta- spores exhibited no increase in either protein carbonyl content
      or oxidized bases in DNA. These data strongly suggest that oxidative damage to
      spore macromolecules does not contribute significantly to spore killing by heat.

PMID- 9758857
TI  - Shedding light on voltage-dependent gating.

PMID- 9758858
TI  - Protein rearrangements underlying slow inactivation of the Shaker K+ channel.
AB  - Voltage-dependent ion channels transduce changes in the membrane electric field
      into protein rearrangements that gate their transmembrane ion permeation
      pathways. While certain molecular elements of the voltage sensor and gates have
      been identified, little is known about either the nature of their conformational
      rearrangements or about how the voltage sensor is coupled to the gates. We used
      voltage clamp fluorometry to examine the voltage sensor (S4) and pore region (P
      region) protein motions that underlie the slow inactivation of the Shaker K+
      channel. Fluorescent probes in both the P-region and S4 changed emission
      intensity in parallel with the onset and recovery of slow inactivation,
      indicative of local protein rearrangements in this gating process. Two sequential
      rearrangements were observed, with channels first entering the P-type, and then
      the C-type inactivated state. These forms of inactivation appear to be mediated
      by a single gate, with P-type inactivation closing the gate and C-type
      inactivation stabilizing the gate's closed conformation. Such a stabilization was
      due, at least in part, to a slow rearrangement around S4 that stabilizes S4 in
      its activated transmembrane position. The fluorescence reports of S4 and P-region
      fluorophore are consistent with an increased interaction of the voltage sensor
      and inactivation gate upon gate closure, offering insight into how the voltage
      sensing apparatus is coupled to a channel gate.

PMID- 9758859
TI  - Structural implications of fluorescence quenching in the Shaker K+ channel.
AB  - When attached to specific sites near the S4 segment of the nonconducting (W434F)
      Shaker potassium channel, the fluorescent probe tetramethylrhodamine maleimide
      undergoes voltage-dependent changes in intensity that correlate with the movement
      of the voltage sensor (Mannuzzu, L.M., M.M. Moronne, and E.Y. Isacoff. 1996.
      Science. 271:213-216; Cha, A., and F. Bezanilla. 1997. Neuron. 19:1127-1140). The
      characteristics of this voltage-dependent fluorescence quenching are different in
      a conducting version of the channel with a different pore substitution (T449Y).
      Blocking the pore of the T449Y construct with either tetraethylammonium or
      agitoxin removes a fluorescence component that correlates with the voltage
      dependence but not the kinetics of ionic activation. This pore-mediated
      modulation of the fluorescence quenching near the S4 segment suggests that the
      fluorophore is affected by the state of the external pore. In addition, this
      modulation may reflect conformational changes associated with channel opening
      that are prevented by tetraethylammonium or agitoxin. Studies of pH titration,
      collisional quenchers, and anisotropy indicate that fluorophores attached to
      residues near the S4 segment are constrained by a nearby region of protein. The
      mechanism of fluorescence quenching near the S4 segment does not involve either
      reorientation of the fluorophore or a voltage-dependent excitation shift and is
      different from the quenching mechanism observed at a site near the S2 segment.
      Taken together, these results suggest that the extracellular portion of the S4
      segment resides in an aqueous protein vestibule and is influenced by the state of
      the external pore.

PMID- 9758861
TI  - Subunit composition determines the single channel kinetics of the epithelial
      sodium channel.
AB  - We have further characterized at the single channel level the properties of
      epithelial sodium channels formed by coexpression of alpha with either wild-type
      beta or gamma subunits and alpha with carboxy-terminal truncated beta (betaT) or
      gamma (gammaT) subunits in Xenopus laevis oocytes. alphabeta and alphabetaT
      channels (9.6 and 8.7 pS, respectively, with 150 mM Li+) were found to be
      constitutively open. Only upon inclusion of 1 microM amiloride in the pipette
      solution could channel activity be resolved; both channel types had short open
      and closed times. Mean channel open probability (Po) for alphabeta was 0.54 and
      for alphabetaT was 0.50. In comparison, alphagamma and alphagammaT channels
      exhibited different kinetics: alphagamma channels (6.7 pS in Li+) had either long
      open times with short closings, resulting in a high Po (0.78), or short openings
      with long closed times, resulting in a low Po (0. 16). The mean Po for all
      alphagamma channels was 0.48. alphagammaT (6.6 pS in Li+) behaved as a single
      population of channels with distinct kinetics: mean open time of 1.2 s and closed
      time of 0.4 s, with a mean Po of 0.6, similar to that of alphagamma. Inclusion of
      0. 1 microM amiloride in the pipette solution reduced the mean open time of
      alphagammaT to 151 ms without significantly altering the closed time. We also
      examined the kinetics of amiloride block of alphabeta, alphabetaT (1 microM
      amiloride), and alphagammaT (0.1 microM amiloride) channels. alphabeta and
      alphabetaT had similar blocking and unblocking rate constants, whereas the
      unblocking rate constant for alphagammaT was 10-fold slower than alphabetaT. Our
      results indicate that subunit composition of ENaC is a main determinant of Po. In
      addition, channel kinetics and Po are not altered by carboxy-terminal deletion in
      the beta subunit, whereas a similar deletion in the gamma subunit affects channel
      kinetics but not Po.

PMID- 9758860
TI  - Effects of spontaneous bilayer curvature on influenza virus-mediated fusion
      pores.
AB  - Cells expressing the hemagglutinin protein of influenza virus were fused to
      planar bilayer membranes containing the fluorescent lipid probes
      octadecylrhodamine (R18) or indocarbocyanine (DiI) to investigate whether
      spontaneous curvature of each monolayer of a target membrane affects the growth
      of fusion pores. R18 and DiI lowered the transition temperatures for formation of
      an inverted hexagonal phase, indicating that these probes facilitate the
      formation of negative curvature structures. The probes are known to translocate
      from one monolayer of a bilayer membrane to the other in a voltage-dependent
      manner. The spontaneous curvature of the cis monolayer (facing the cells) or the
      trans monolayer could therefore be made more negative through control of the
      polarity of voltage across the planar membrane. Electrical admittance
      measurements showed that the open times of flickering fusion pores were shorter
      when probes were in trans monolayers and longer when in cis monolayers compared
      with times when probe was symmetrically distributed. Open times were the same for
      probe symmetrically distributed as when probes were not present. Thus, open times
      were a function of the asymmetry of the spontaneous curvature between the trans
      and cis monolayers. Enriching the cis monolayer with a negative curvature probe
      reduced the probability that a small pore would fully enlarge, whereas enriching
      the trans monolayer promoted enlargement. Lysophosphatidylcholine has positive
      spontaneous curvature and does not translocate. When lysophosphatidylcholine was
      placed in trans leaflets of planar membranes, closing of fusion pores was rare.
      The effects of the negative and positive spontaneous curvature probes do not
      support the hypothesis that a flickering pore closes from an open state within a
      hemifusion diaphragm (essentially a "flat" structure). Rather, such effects
      support the hypothesis that the membrane surrounding the open pore forms a three
      dimensional hourglass shape from which the pore flickers shut.

PMID- 9758862
TI  - Permeation and gating of an inwardly rectifying potassium channel. Evidence for a
      variable energy well.
AB  - Permeation, gating, and their interrelationship in an inwardly rectifying
      potassium (K+) channel, ROMK2, were studied using heterologous expression in
      Xenopus oocytes. Patch-clamp recordings of single channels were obtained in the
      cell-attached mode. The gating kinetics of ROMK2 were well described by a model
      having one open and two closed states. One closed state was short lived
      (approximately 1 ms) and the other was longer lived (approximately 40 ms) and
      less frequent (approximately 1%). The long closed state was abolished by EDTA,
      suggesting that it was due to block by divalent cations. These closures exhibit a
      biphasic voltage dependence, implying that the divalent blockers can permeate the
      channel. The short closures had a similar biphasic voltage dependence, suggesting
      that they could be due to block by monovalent, permeating cations. The rate of
      entering the short closed state varied with the K+ concentration and was
      proportional to current amplitude, suggesting that permeating K+ ions may be
      related to the short closures. To explain the results, we propose a variable
      intrapore energy well model in which a shallow well may change into a deep one,
      resulting in a normally permeant K+ ion becoming a blocker of its own channel.

PMID- 9758863
TI  - Effect of membrane tension on gap junctional conductance of supporting cells in
      Corti's organ.
AB  - The effects of turgor pressure-induced membrane tension on junctional coupling of
      Hensen cell isolates from the inner ear were evaluated by input capacitance or
      transjunctional conductance measurement techniques. Turgor pressure was altered
      by changing either pipette pressure or the osmolarities of extracellular
      solutions. Both positive pipette pressure and extracellular applications of
      hypotonic solutions, which caused cell size to concomitantly increase, uncoupled
      the cells as indicated by reduced input capacitance and transjunctional
      conductance. These changes were, in many cases, reversible and repeatable.
      Intracellular application of 50 microM H-7, a broad-based protein kinase
      inhibitor, and 10 mM BAPTA did not block the uncoupling effect of positive turgor
      pressure on inner ear gap junctions. The transjunctional conductance at a holding
      potential of -80 mV was 53.6 +/- 5.8 nS (mean +/- SEM, n = 9) and decreased
      approximately 40% at a turgor pressure of 1.41 +/- 0.05 kPa. Considering the
      coincident kinetics of cell deformation and uncoupling, we speculate that
      mechanical forces work directly on gap junctions of the inner ear. These results
      suggest that pathologies that induce imbalances in cochlear osmotic pressure
      regulation may compromise normal cochlear homeostasis.

PMID- 9758864
TI  - Intermediate conductances during deactivation of heteromultimeric Shaker
      potassium channels.
AB  - A previous study of the T442S mutant Shaker channel revealed activation-coupled
      subconductance levels that apparently represent kinetic intermediates in channel
      activation (Zheng, J., and F.J. Sigworth. 1997. J. Gen. Physiol. 110:101-117). We
      have now extended the study to heteromultimeric channels consisting of various
      numbers of mutant subunits as well as channels without mutant subunits, all in
      the background of a chimeric Shaker channel having increased conductance. It has
      been found that activation-coupled sublevels exist in all these channel types,
      and are traversed in at least 80% of all deactivation time courses. In symmetric
      K+ solutions, the currents in the two sublevels have a linear voltage dependence,
      being 23-44% and 54-70% of the fully open conductance. Sublevels in different
      channel types share similar voltage dependence of the mean lifetime and similar
      ion selectivity properties. However, the mean lifetime of each current level
      depends approximately geometrically on the number of mutant subunits in the
      channel, becoming shorter in channels having fewer mutant subunits. Each mutant
      subunit appears to stabilize all of the conducting states by approximately 0.5
      kcal/mol. Consistent with previous results in the mutant channel, sublevels in
      channels with two or no mutant subunits also showed ion selectivities that differ
      from that of the fully open level, having relatively higher K+ than Rb+
      conductances. A model is presented in which Shaker channels have two coupled
      activation gates, one associated with the selectivity filter and a second
      associated with the S6 helix bundle.

PMID- 9758865
TI  - Nonindependent K+ movement through the pore in IRK1 potassium channels.
AB  - We measured unidirectional K+ in- and efflux through an inward rectifier K
      channel (IRK1) expressed in Xenopus oocytes. The ratio of these unidirectional
      fluxes differed significantly from expectations based on independent ion
      movement. In an extracellular solution with a K+ concentration of 25 mM, the data
      were described by a Ussing flux-ratio exponent, n', of approximately 2.2 and was
      constant over a voltage range from -50 to -25 mV. This result indicates that the
      pore of IRK1 channels may be simultaneously occupied by at least three ions. The
      IRK1 n' value of 2.2 is significantly smaller than the value of 3.5 obtained for
      Shaker K channels under identical conditions. To determine if other permeation
      properties that reflect multi-ion behavior differed between these two channel
      types, we measured the conductance (at 0 mV) of single IRK1 channels as a
      function of symmetrical K+ concentration. The conductance could be fit by a
      saturating hyperbola with a half-saturation K+ activity of 40 mM, substantially
      less than the reported value of 300 mM for Shaker K channels. We investigated the
      ability of simple permeation models based on absolute reaction rate theory to
      simulate IRK1 current-voltage, conductance, and flux-ratio data. Certain classes
      of four-barrier, three-site permeation models are inconsistent with the data, but
      models with high lateral barriers and a deep central well were able to account
      for the flux-ratio and single channel data. We conclude that while the pore in
      IRK1 and Shaker channels share important similarities, including K+ selectivity
      and multi-ion occupancy, they differ in other properties, including the
      sensitivity of pore conductance to K+ concentration, and may differ in the number
      of K+ ions that can simultaneously occupy the pore: IRK1 channels may contain
      three ions, but the pore in Shaker channels can accommodate four or more ions.

PMID- 9758866
TI  - Mechanism of maxi-K channel activation by dehydrosoyasaponin-I.
AB  - Dehydrosoyasaponin-I (DHS-I) is a potent activator of high-conductance, calcium
      activated potassium (maxi-K) channels. Interaction of DHS-I with maxi-K channels
      from bovine aortic smooth muscle was studied after incorporating single channels
      into planar lipid bilayers. Nanomolar amounts of intracellular DHS-I caused the
      appearance of discrete episodes of high channel open probability interrupted by
      periods of apparently normal activity. Statistical analysis of these periods
      revealed two clearly separable gating modes that likely reflect binding and
      unbinding of DHS-I. Kinetic analysis of durations of DHS-I-modified modes
      suggested DHS-I activates maxi-K channels through a high-order reaction. Average
      durations of DHS-I-modified modes increased with DHS-I concentration, and
      distributions of these mode durations contained two or more exponential
      components. In addition, dose-dependent increases in channel open probability
      from low initial values were high order with average Hill slopes of 2.4-2.9 under
      different conditions, suggesting at least three to four DHS-I molecules bind to
      maximally activate the channel. Changes in membrane potential over a 60-mV range
      appeared to have little effect on DHS-I binding. DHS-I modified calcium- and
      voltage-dependent channel gating. 100 nM DHS-I caused a threefold decrease in
      concentration of calcium required to half maximally open channels. DHS-I shifted
      the midpoint voltage for channel opening to more hyperpolarized potentials with a
      maximum shift of -105 mV. 100 nM DHS-I had a larger effect on voltage-dependent
      compared with calcium-dependent channel gating, suggesting DHS-I may
      differentiate these gating mechanisms. A model specifying four identical,
      noninteracting binding sites, where DHS-I binds to open conformations with 10-20
      fold higher affinity than to closed conformations, explained changes in voltage
      dependent gating and DHS-I-induced modes. This model of channel activation by DHS
      I may provide a framework for understanding protein structures underlying maxi-K
      channel gating, and may provide a basis for understanding ligand activation of
      other ion channels.

PMID- 9758868
TI  - [Val384Asp in hMLH1 gene in Chinese, Japanese and German and its etiological role
      in colorectal cancer].
AB  - OBJECTIVE: To investigate Va1384Asp of hMLH1 gene in Chinese, Japanese and German
      after the missense mutation were identified in Chinese colorectal cancer patients
      and to inquire into the etiological role of this mutation in colorectal cancer.
      METHODS: Genomic DNA extracted from normal colon tissue or peripheral blood were
      subjected to analysis in exon 12 of the hMLH1 gene by single strand conformation
      polymorphism (SSCP) followed by DNA sequencing of aberrant bands in 26 Chinese
      and 109 German colorectal cancer patients and in 80 healthy Chinese, 80 Japanese
      and 100 German individuals . RESULTS: Va1384Asp in hMLH1 gene was found in 4 out
      of 26 Chinese colorectal patients; 3 of them were out of the 9 patients with
      colorectal cancer at young age (<50 years). Although 3 and 4 carriers of
      Va1384Asp in hMLH1 gene were identified in 80 healthy Chinese and 80 healthy
      Japanese individuals respectively, none were identified in German neither in 109
      colorectal cancer patients, nor in 100 healthy German individuals. The frequency
      of Va1384Asp in hMLH1 gene in the Chinese with colorectal cancer at young age was
      higher than that in Chinese healthy individuals (P=0.013). CONCLUSION: Va1384Asp
      can be taken as a polymorphism in hMLH1 gene in Chinese and Japanese populations
      and may have a potential effect on age at onset of colorectal cancer.

PMID- 9758870
TI  - [The microsatellite instability and loss of heterozygosity in chromosome
      translocation breakpoint in leukemia].
AB  - OBJECTIVE: To investigate the microsatellite instability (MSI) and loss of
      heterozygosity (LOH) near the chromosome translocation breakpoints of various
      types of leukemia. METHODS: PCR amplification of 11 microsatellite loci closely
      linked to chromosome translocation breakpoints in 30 leukemia patients. RESULTS:
      Twenty one in 30 cases of leukemia had MSI in from 1 to 14 microsatellite loci.
      Eleven in 15 cases of acute leukemia had microsatellite instability (MSI) in more
      than 1 locus; among them 4 cases had MSI in from 7 to 11 loci. In order of MSI
      presence rate were D22S315>D9S179>D16S515>D8S559>D12S89. In six cases of chronic
      myeloid leukemia, 4 cases had MSI in more than 3 loci. Thirteen (2/15) percent of
      acute leukemia patients had loss of heterozygosity (LOH); the rate was higher
      than that in other leukemia types. CONCLUSION: The results of MSI and LOH in many
      cases indicate that there are a lot of allelic alterations in leukemia patients,
      but those changes have no special relationship with chromosome translocation
      breakpoints in various leukemia types.

PMID- 9758869
TI  - [Establishment of partial gene expression map of 7q32 in nasopharyngeal carcinoma
      and primary culture normal nasopharyngeal epithelial cells].
AB  - OBJECTIVE: To establish partial gene expression map of 7q32 in nasopharyngeal
      carcinoma (NPC) cell line, tissues and primary culture normal nasopharyngeal
      epithelial cells. METHODS: We detected the expression of 20 ESTs at 7q32 in NPC
      cell line HNE1,13 NPC biopsies and primary culture normal nasopharyngeal
      epithelial cells using differential RT PCR and Northern hybridization. RESULTS: 8
      ESTs (AA188181, AA13079,N27556, AA031919, N22721, H20825, T91284, AA001936)
      expressed equally in both of HNE1 and primary culture normal nasopharyngeal
      epithelial cells; 7 ESTs (T64215, AA025822, R60014,R80002,H06688, R60192,R95096)
      expressed in neither of them; 3 ESTs (H19830,W72688,AA130630) overexpressed in
      HNE1 ; and 2 ESTs (AA070437, H90882) overexpressed in primary culture normal
      nasopharyngeal epithelial cells. W72688 and H19830 each overexpressed in
      77%(10/13) of NPC biopsies; AA070437 down-expressed in 30.7% of NPC biopsies.
      CONCLUSION: Partial gene expression map of 7q32 in nasopharyngeal carcinoma cell
      line ,tissues and primary culture normal nasopharyngeal epithelial cells has been
      established. The up-regulation of W72688, H19830 and down-regulation of AA070437
      may be related to the occurrence of NPC.

PMID- 9758871
TI  - [Loss of heterozygosity microsatellite DNA on chromosome loci 3, 5, 7, 9 and 18
      in human pancreatic cancer].
AB  - OBJECTIVE: Detecting the loss of heterozygosity in paraffin-embedded pancreatic
      cancer tissues. METHODS: Analysing loss of heterzygosity (LOH) of microsatellite
      DNA on chromosome loci 3,5,7,9 and 18 with PCR-SSLP-silver stain method in
      pancreatic cancer. RESULTS: In 45 sporadic pancreatic cancer samples and their
      paired control tissue, LOH was detected on site for D18S46( 18q21.1,31.0%),
      D18S474 (18q21.1, 20.0%), D9S176 (9q22-31,20.0%), D3S1234 (3p14.2,17.5%),D 3S1289
      (3p21.1, 15.7%), D3S1481 (3p14.2,4.9%), D7S486 (7q22,3.6%), D5S365 (5q32, 3.2%)
      and D3S587 (3p24-26, 2.6%). CONCLUSION: Different percentages of loss of
      heterzygosity on specific chromosomal regions were found, and the meaning of the
      results was discussed. Some key genes may play a role in the pathogenesis of
      pancreatic cancer.

PMID- 9758867
TI  - Temperature dependence of voltage-gated H+ currents in human neutrophils, rat
      alveolar epithelial cells, and mammalian phagocytes.
AB  - H+ currents in human neutrophils, rat alveolar epithelial cells, and several
      mammalian phagocyte cell lines were studied using whole-cell and excised-patch
      tight-seal voltage clamp techniques at temperatures between 6 and 42 degrees C.
      Effects of temperature on gating kinetics were distinguished from effects on the
      H+ current amplitude. The activation and deactivation of H+ currents were both
      highly temperature sensitive, with a Q10 of 6-9 (activation energy, Ea,
      approximately 30-38 kcal/mol), greater than for most other ion channels. The
      similarity of Ea for channel opening and closing suggests that the same step may
      be rate determining. In addition, when the turn-on of H+ currents with
      depolarization was fitted by a delay and single exponential, both the delay and
      the time constant (tauact) had similarly high Q10. These results could be
      explained if H+ channels were composed of several subunits, each of which
      undergoes a single rate-determining gating transition. H+ current gating in all
      mammalian cells studied had similarly strong temperature dependences. The H+
      conductance increased markedly with temperature, with Q10 >/= 2 in whole-cell
      experiments. In excised patches where depletion would affect the measurement
      less, the Q10 was 2.8 at >20 degrees C and 5.3 at <20 degrees C. This temperature
      sensitivity is much greater than for most other ion channels and for H+
      conduction in aqueous solution, but is in the range reported for H+ transport
      mechanisms other than channels; e.g., carriers and pumps. Evidently, under the
      conditions employed, the rate-determining step in H+ permeation occurs not in the
      diffusional approach but during permeation through the channel itself. The large
      Ea of permeation intrinsically limits the conductance of this channel, and
      appears inconsistent with the channel being a water-filled pore. At physiological
      temperature, H+ channels provide mammalian cells with an enormous capacity for
      proton extrusion.

PMID- 9758872
TI  - [Detection of Hep-2 and hepatoma cell line chromosomal aberration by using
      fluorescence in situ hybridization].
AB  - OBJECTIVE: To study the chromosomal aberration of hepatoma cell line (1172) and
      laryngocarcinoma cell line (Hep-2). METHODS: Fluorescence in situ hybridization
      (FISH) was used with nine chromosomal special libraries. RESULTS: The abnormal
      signals indicated that very complicated aberrations existed in the two cell
      lines. This suggested that the aberrations also existed in other chromosomes not
      yet studied. In 1172, the major type was structure aberration, but in Hep-2,
      numerical abnormality was shown in almost all chromosomes studied. CONCLUSION:
      Compared with traditional cytological methods, this technique has the advantages
      of being quicker and more accurate and sensitive.

PMID- 9758873
TI  - [Association between the debrisoquine hydroxylase gene polymorphism and the
      genetic susceptibility of Parkinson's disease].
AB  - OBJECTIVE: To clarify the relation of the debrisoquine hydroxylase gene
      polymorphism with the genetic susceptibility of Parkinson's disease. METHODS: The
      debrisoquine hydroxylase gene polymorphisms were analyzed with the polymerase
      chain reaction-restriction fragment length polymorphism methods in 100 cases of
      Parkinson's disease and 100 age-,sex-matched normal controls. RESULTS: It was
      found that the frequencies of A and B mutation of debrisoquine hydroxylase gene
      in group of patients were higher than those in the controls, and the risk of
      suffering Parkinson's disease increased 2 times. In group of the patients, the
      frequencies of C188-->T, G4268-->C and C2938-->T were also higher than those in
      the controls. Especially in those with C2938-->T mutation, the risk of suffering
      the disease increased 2.58 times. CONCLUSION: The result suggested that the
      defect of the detoxifying enzymes might be a factor contributing to the genetic
      susceptibility of Parkinson's disease.

PMID- 9758874
TI  - [Identification of a mutation hotspot in exon 8 of Wilson's disease gene by cycle
      sequencing].
AB  - OBJECTIVE: To screen for mutation hotspot of Wilson's disease (WD) gene in
      Chinese. METHODS: Cycle sequencing was used to detect mutation in exon 8 of WD
      gene in 30 patients with WD. RESULTS: The same missense mutation, Arg778Leu, was
      identified in 14 WD patients, four of which were homozygous and the others were
      heterozygous for this mutation. The frequency of this mutation was 30%.
      CONCLUSION: The codon 778(CGG-->CTG) of exon 8 in WD gene was one of mutation
      hotspots in Chinese.

PMID- 9758875
TI  - [A study of correlation between essential hypertension and HLA-DQA1 alleles].
AB  - OBJECTIVE: To analyse the hereditary susceptibility by genotyping of HLA-DQA1
      alleles in essential hypertensives. METHODS: The allelic types of HLA-DQA1 were
      detected by PCR-SSP technic in 52 cases of essential hypertensives and 86 normal
      individuals as the control. RESULTS: The frequency of HLA-DQA1*0302 allele in
      hypertensive group was markedly higher than that in normal control group (17.9572
      vs 3.5531), but the frequency of HLA-DQA1*0103 allele in normal group was higher
      than that in hypertensive group. CONCLUSION: HLA-DQA1*0302 may be a correlative
      gene of essential hypertension, whereas HLA-DQA1*0103 may be a defence gene of
      hypertension.

PMID- 9758876
TI  - [Expression of human SRY gene and the DNA-binding property of its product].
AB  - OBJECTIVE: To investigate the role which human SRY gene plays in the regulation
      of the downstream gene. METHODS: The fragment of SRY (sex determinating region on
      the Y chromosome) HMG domain was cloned into the expressing vector pET-15b. The
      hSRY gene recombinant plasmid-pETSY was transformed and expressed in E.coliBL21.
      The target protein was purified by pET His. Tag system. The DNA-binding
      retardation test and its competitive reaction were conducted between SRY protein
      and the fragment of Mullerian inhibiting substance (MIS) promoter. RESULTS: The
      molecular weight of the expressed hSRY protein was shown to be approximately
      21kD. The specific DNA binding property of SRY protein to the fragment of MIS was
      confirmed in the retardation test and its competitive reaction. CONCLUSION: The
      results suggest that the product of SRY gene can bind the MIS promoter region and
      may initiate the transcription of MIS.

PMID- 9758877
TI  - [Genetic polymorphisms of TH01 and VWA loci in Tibetans in China].
AB  - OBJECTIVE: To understand the genetic relationship between Han population and
      Tibetan population, the genetic polymorphisms of two STR loci, TH01 and VWA were
      studied in the Tibetans in China. METHODS: EDTA-blood specimens were collected
      from 89 healthy unrelated Tibetan individuals in Lasa. DNA was extracted using
      Chelex method. The DNA samples were amplified by PCR technique, and the PAGE
      horizontal electrophoresis were used to typing the PCR products. RESULTS: There
      were five alleles at TH01 locus in Tibetan population. The alleles frequencies
      were TH01*6:0.097, TH01*7:0.227, TH01*8:0.091, TH01*9:0.481 and TH01*9.3:0.104. A
      total of 12 genotypes were observed in 77 individuals for TH01. For VWA locus
      there were seven alleles and the allele frequencies were VWA *14:0.101,
      VWA*15:0.034, VWA*16:0.208, VWA*17:0.303, VWA*18:0.208, VWA*19:0.129 and
      VWA*20:0.017. A total of 20 genotypes for VWA were observed in 89 individuals.
      The results of test for Hardy-Weinberg equilibrium showed that the genotype
      distributions observed at both STR loci were correspondent with those
      expected(chi-square =7.421 df =8 P>0.05 for TH01; chi-square =19.61 df =14 P>0.05
      for VWA). CONCLUSION: There is no significant difference between Han and Tibetan
      populations in allele frequencies at TH01 and VWA loci. The results of analysis
      using genetic distance and phylogenetic tree indicate that Tibetan population is
      identical with Han population at TH01 and VWA loci .

PMID- 9758878
TI  - [Comparison of genotype and intellectual phenotype in untreated phenylketonuric
      children].
AB  - OBJECTIVE: The main feature of phenylketonuria(PKU) is mental retardation.
      Although classical PKU is defined as that the hepatic phenylalanine hydroxylase
      (PAH) activity ranges 0-1% of normal enzyme, the untreated PKU patients show a
      wide range of intellectual phenotype. This study sought to find the molecular
      basis of such variation of intellectual phenotype among PKU. METHODS: 45
      classical PKU patients included in the research were screened for detecting six
      mutant alleles which were rather common among Chinese PKU patients, i.e. R243Q,
      R413P, Y204C, Y356X, W326X and R111X. PCR-ASO and PCR-SSCP techniques were used.
      The expression of those mutant PAH genes was analysed by methods of site-directed
      mutagencies. 27 PKU patients whose two mutant alleles were both defined were
      involved in this study. The IQ of these patients were tested by DDST system.
      RESULTS: Among 27 patients, 4/27 (15%) were mild retardation, 10/27(37%) were
      moderate, the severe mental retardation accounted for 12/27(44%). The
      relationship between genotype and intellectual phenotype in this group was
      examined. It was found that the intellectual phenotype of 8 patients were
      compatible with genotype but not well matched in 19 cases. The enzyme activity of
      Y204C expressed in vitro was 100%, but all 3 patients with Y204C/Y204C were
      severely mental retarded. Enzyme activities of R413P and Y356X were <3% and 0
      respectively in expression analysis, but the patients in this group had mild or
      moderate mental retardation. CONCLUSION: Intellectual phenotype was not well
      matched with the genotype in classical PKU patients, so that genotype can not be
      used to predicte the intellectual phenotype in PKU patients.

PMID- 9758879
TI  - [Relationship between methylenetetrahydrofolate reductase gene polymorphism and
      coronary heart disease].
AB  - OBJECTIVE: This study inquired into the relationship between
      methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and coronary heart
      disease. METHODS: By polymerase chain reaction and restriction fragment length
      polymorphism (PCR-RFLP), MTHFR 677C-->T mutation was detected in 79 healthy
      controls and 69 patients with coronary heart disease. RESULTS: The frequency of
      MTHFR variant V677 of patients was significantly higher than that of healthy
      controls (P<0.01). CONCLUSION: This study demonstrated that MTHFR gene V677
      mutation was probably one of the genetic risk factors of coronary heart disease
      and this provided a new basis for exploring the relevant pathogenesis.

PMID- 9758880
TI  - [A family study of obsessive-compulsive disorder].
AB  - OBJECTIVE: To explore the genetic etiology of obsessive-compulsive disorder (OCD)
      and genetic association between OCD and tic disorder. METHODS: The mental
      disorders in the first degree and second degree relatives of 90 probands with OCD
      were investigated and compared with those of 100 healthy families by the method
      of family genetic study. RESULTS: Compared to the control, the prevalence rates
      of schizophrenia, affective disorder, minor depression, subclinical OCD, general
      anxiety disorder and tic disorder in the first degree relatives of OCD were
      elevated, except that of OCD. The prevalence rates of OCD and subclinical OCD,
      general anxiety disorder, and other neurotic disorders in the first degree
      relatives of patients with pure obsession were 47.6%, 35.7% and 23.8%,
      respectively; compared to 10.8%, 3.6% and 0 in those of the control (P<0.01). The
      prevalence rates of schizophrenia,affective disorder,and tic disorder in the
      first degree relatives of OCD with tic were 52.0%, 26.0% and 90.9%, respectively;
      compared to 0, 3.6% and 7.2% in those of the control (P<0.01). CONCLUSION: The
      etiology of OCD is related to heredity. There was evidence to show genetic
      association between OCD and tic disorder,The elevation of prevalence rates of
      various mental disorders in the first degree relatives of OCD might suggest the
      genetic basis of various subtypes of OCD.

PMID- 9758881
TI  - [Screening mutations in phenylketonuria by means of nonradioactive reverse dot
      blot hybridization].
AB  - OBJECTIVE: To establish a simple, accurate and rapid method for screening of the
      mutant genes in phenylketonuria (PKU). METHODS: Four exons harboring the
      mutations, Y204C (exon6, E6), R243Q(E7), Y356X(E11) and R413P(E12), were
      amplified by polymerase chain reaction (PCR) with incorporation of biotinylated
      deoxynucleotide(biotinylated-11-dUTP or biotinylated-14-dCTP). Hybridization
      between immobilized allele-specific oligonucleotide probes and biotin-labelled
      amplified DNA was performed and nonradioactively detected by a colorimetric
      reaction using streptavidin-alkaline phosphatase. RESULTS: The methods of non
      radioactive reverse dot blot hybridization were established to screen the
      mutations. We detected the genotypes of five PKU patients and found that three of
      them carried R243Q mutation and one of the three also carried Y356X mutation.
      These results were confirmed by PCR-single strand conformation polymorphism.
      CONCLUSION: This method is suitable for rapid screening for common mutations in
      Chinese PKU patients.

PMID- 9758882
TI  - [PCR in combination with silver as a method for the determination of
      apolipoprotein E alleles].
AB  - OBJECTIVE: To present a rapid, sensitive and safe procedure for the determination
      of human apolipoprotein E alleles. METHODS: Genomic DNA was extracted from 0.5ml
      whole blood by a non-phenol protocol. After PCR and restriction enzyme
      digestion,short DNA fragments were detected by a simplified silver staining
      method. This technique was used to assay apolipoprotein E alleles in 19 patients
      with sporadic Alzheimer's disease and 41 normal aged persons. RESULTS: The short
      DNA fragments were visualized clearly on polyacrylamide gel processed by silver
      staining. It took 24 hours from DNA extraction to the final result. The A4 allele
      frequency in patients with sporadic Alzheimer's disease was 0.29, much higher
      than that in control group (0.02, P<0.001). CONCLUSION: PCR in combination with
      silver staining can satisfy the need for high-resolution and high-efficiency in
      the determination of apolipoprotein E alleles and can be used as a routine
      procedure in clinical and epidemiological investigations.

PMID- 9758883
TI  - On the problem of adequate language in motor control.
AB  - An adequate language is a prerequisite for progress in any area of science,
      including movement science. Notions of structural units and synergies and the
      principle of minimal interaction are revisited, discussed, and illustrated with a
      few examples from recent studies. Equilibrium-point hypothesis is considered an
      example of identifying significant variables in the control of a voluntary
      movement.

PMID- 9758884
TI  - Coactivation to reduce variability in the elderly.
AB  - The aim of this experiment was to determine whether elderly persons exhibit
      reciprocal phasing of muscle activity and scale EMG burst amplitude in the same
      manner as young people. Seven young and 7 elderly adults performed 30( elbow
      flexion movements at 800 ms duration to a visual target against varying inertial
      loads. The elderly were not able to achieve the required movement duration as
      frequently and spent a greater portion of the movement accelerating than the
      young. The young and the elderly subjects scaled EMG burst amplitude to the
      increasing loads in the same fashion, although the elderly subjects coactivated
      the agonist/antagonist muscles more than did the young subjects and thus did not
      accelerate the limb as rapidly. We hypothesized that the elderly used
      coactivation to reduce movement variability, and we developed a single-joint
      model with two muscles to examine this hypothesis. The model simulation correctly
      predicted the variability reduction due to coactivation. It appears, however,
      that this reduces the capability to accelerate rapidly.

PMID- 9758885
TI  - Path curvature in workspace and in joint space: evidence for coexisting
      coordinative rules in aiming.
AB  - In this study we tried to establish whether point-to-point aiming movements are
      planned in workspace, joint space, or both. Eight right-handed subjects performed
      horizontal, vertical, and diagonal aiming movements on a transversal plane.
      Movements were performed at several speeds. Curvature variations of the hand and
      corresponding joint-space paths were investigated as a function of position,
      direction, and speed. Straightness of hand paths predominated for vertical
      movements but was systematically violated for horizontal and top-right to bottom
      left movements. Furthermore, the hand-path curvature of the latter movements
      increased with speed. Joint-space paths showed more deviation from a straight
      line than hand paths except for top-left to bottom-right movements in which the
      paths were equally curved. A comparison of normalized path curvatures at the hand
      and joint level indicated that in aiming, the coordinative rule of straight-line
      production seems to apply to both workspace and joint-space planning. The present
      findings confirm Kawato's (1996) views that optimization processes operate
      concurrently at the two control levels of arm-trajectory formation under study.

PMID- 9758886
TI  - Grasp stiffness as a function of grasp force and finger span.
AB  - The purpose of this study was to determine whether direct measurements of grasp
      stiffness agreed with stiffness inferred from the slopes of isovolitional force
      space characteristics derived from previous grasp-effort matching data. Grasp
      stiffness for three-finger pinch was measured as a function of initial force and
      finger span using step displacements applied in a do-not-intervene paradigm.
      Subjects pinched a free-floating, motorized manipulandum in each hand and
      squeezed both with equal effort; one of the hands was perturbed at random.
      Stiffness was calculated from the initial and final steady-state values of force
      and span. The effects of step amplitude, rise-time, and initial load stiffness
      were investigated; grasp stiffness decreased significantly for larger steps,
      increased slightly for longer rise-times, and was unaffected by load stiffness.
      Grasp stiffness then was measured as a function of initial force and span using a
      single set of step parameters. Stiffness increased significantly in proportion to
      force but was changed only slightly by span. It was concluded that the
      perturbation and effort-matching measures of stiffness are not equivalent and
      represent different components of motor behavior.

PMID- 9758887
TI  - The involvement of CD80 and CD86 costimulatory molecules in the induction of
      eosinophilia in mice infected with Nippostrongylus brasiliensis.
AB  - The costimulatory signal provided by the interaction between CD28 and its
      ligands, CD80 and CD86, is critical for T cell activation. The requirement of
      CD80 and CD86 in T cell activation for eosinophilia and IgE production was
      examined in mice infected with the nematode parasite Nippostrongylus
      brasiliensis. Combined treatment with anti-CD80 and anti-CD86 suppressed
      eosinophilia in the blood and the small intestine and suppressed IgE production.
      However, administration of either anti-CD80 or anti-CD86 alone had little effect
      on eosinophilia and on the elevation of IgE levels. These results suggest that
      CD80 and CD86 costimulation is required and either CD80 or CD86 can provide a
      sufficient costimulatory signal for induction of eosinophilia in mice infected
      with N. brasiliensis.

PMID- 9758888
TI  - Identification of cDNA for rat homologues of human major basic protein and
      eosinophil cationic protein.
AB  - We have determined the complete nucleotide sequence for cDNA of rat homologues of
      human eosinophil major basic protein (MBP) and eosinophil cationic protein (ECP)
      using the rapid amplification of cDNA ends (RACE) procedure. Nucleotide sequence
      of cDNA of rat MBP revealed that mRNA of rat MBP encodes a protein containing 227
      amino acids which has three functional domains; namely, the signal peptide, the
      acidic peptide that contains numerous acidic amino acids and the mature MBP, as
      in human, guinea pig and mouse MBP. In addition, cDNA of a rat homologue of human
      ECP was also cloned. The deduced amino acid sequence revealed that this gene
      encodes a putative protein with a molecular weight of 15.5 kD which has
      ribonuclease activity. The homology of amino acid sequence between the rat
      homologue and the murine eosinophil-associated ribonucleases (EARs) was high
      (65%). Therefore, we named this rat homologue 'rat EAR-1'.

PMID- 9758889
TI  - Modulation of normal human eosinophil chemotaxis in vitro by herbimycin A,
      erbstatin and pervanadate.
AB  - BACKGROUND: The mediators involved in eosinophil accumulation in diseases such as
      allergy continue to be an area of interest, even though little is known regarding
      the signaling involved in the human cell type recruitment. In the present study,
      we demonstrate a novel modulatory role of tyrosine kinase and tyrosine
      phosphatase activities on normal human eosinophil chemotaxis induced by different
      groups of chemoattractant. METHODS: Purified eosinophils were obtained from
      normal healthy volunteers with the CD16-negative procedure. Chemotactic
      activities against platelet-activating factor (PAF), vasoactive intestinal
      peptide (VIP) and eotaxin were assessed using a 48-well microchemotaxis chamber
      assay. Purified eosinophils were pretreated with herbimycin A, erbastatin or
      pervanadate to examine the role of tyrosine kinase in chemoattractant signaling.
      RESULTS: Pretreatment of eosinophils with the tyrosine kinase inhibitors
      herbimycin A and erbstatin significantly blocked chemotaxis induced by eotaxin
      whilst both inhibitors augmented chemotaxis induced by VIP; however, they had no
      effect on PAF-induced chemotaxis. On the other hand, pretreatment of eosinophils
      with the phosphotyrosine phosphatase inhibitor pervanadate resulted in
      augmentation of eotaxin-induced chemotaxis and inhibition of VIP-induced
      chemotaxis, but it had no effect on PAF-induced chemotaxis. CONCLUSIONS: These
      results suggest that protein kinase plays a modulatory role in eosinophil
      chemotaxis induced by various chemoattractants.

PMID- 9758890
TI  - Blockade of CD28/B7 interaction suppresses allergic eosinophilic inflammation in
      mice.
AB  - To determine whether the costimulatory signal via CD28/B7 interaction is required
      for causing allergic inflammation, we examined the effect of administration of
      CTLA4-Ig, a fusion protein of the extracellular domain of CTLA4 and human IgG1
      constant region, at the time of sensitization, on antigen-induced eosinophil
      infiltration in the trachea of sensitized mice, on IL-2, IFN-gamma, IL-4 and IL-5
      production in the airways of the mice and on antigen-specific IgE synthesis in
      the mice. Administration of CTLA4-Ig at the time of sensitization suppressed
      antigen-induced eosinophil infiltration into the trachea and antigen-specific IgE
      production in mice. Furthermore, CTLA4-Ig administration at the time of
      sensitization suppressed not only IL-2 production but also IFN&hyphengamma and
      Th2 cytokine IL-4 and IL-5 production in the airways. Because allergic
      inflammation requires CD4+ T cells producing Th2-type cytokines IL-4 and IL-5,
      our results suggest that the costimulatory signal via CD28/B7 interaction is
      important for the generation and activation of Th2 cells and thereby for the
      development of allergic inflammation.

PMID- 9758891
TI  - Effect of immunotherapy on the production of eosinophil adhesion-inducing
      activity from mononuclear cells in house-dust-mite-sensitive bronchial asthma.
AB  - An initial step of eosinophil (EOS) accumulation in the sites of allergic
      inflammation is the adhesion to endothelial cells. There is increasing evidence
      that immunotherapy (IT) modulates the production of cytokines from mononuclear
      cells and hence attenuates allergic inflammation. To examine whether IT modifies
      the production of factor(s) which induce EOS adhesion, peripheral blood
      mononuclear cells (PBMC) from house-dust-mite-sensitive asthmatics treated with
      or without IT were cultured for 96 h in the presence or absence of 1/microg/ml
      Dermatophagoides farinae antigen. EOS were isolated from the peripheral blood of
      healthy subjects. EOS adhesion-inducing activity (EAIA) in the PBMC culture
      supernatants was examined by the ability to modify EOS adhesion to
      paraformaldehyde-fixed human umbilical vein endothelial cells (HUVEC) which were
      stimulated with IL-4 plus TNF-alpha. In asthmatics without IT, the addition of D.
      farinae antigen significantly promoted the production of EAIA from PBMC (EOS
      adhesion: 22.4+/-13.1% by medium control vs. 30.5+/-18.9% by D. farinae, n=10,
      p=0.023). This enhancing effect was blocked by an anti-beta2-integrin antibody.
      In contrast, the addition of D. farinae did not modulate EAIA production from
      PBMC in asthmatics treated with IT (23.1+/-10.3% vs. 21.5+/-12.3%, n=10, p=NS).
      These results suggest that IT induces the inhibition of antigen-dependent
      production of EAIA from PBMC. This may contribute to the inhibitory effect of IT
      on eosinophil recruitment in allergic inflammation.

PMID- 9758892
TI  - IL-5-producing T cells that induce airway eosinophilia and hyperresponsiveness
      are suppressed by dexamethasone and cyclosporin A in mice.
AB  - We have recently demonstrated that airway eosinophilic inflammation can be
      transferred to unprimed mice by infusion of IL-5-producing T cell clones. In this
      study, we investigated the effects of dexamethasone and cyclosporin A on the
      airway eosinophilic inflammation in mice transferred with T cell clones. An
      ovalbumin-reactive T cell clone, KW29, produced IL-5 as well as IL-2 and IL-4
      upon stimulation with relevant antigen. Dexamethasone and cyclosporin A dose
      dependently suppressed the production of these cytokines in vitro. The number of
      eosinophils recovered in the bronchoalveolar lavage fluid and the airway
      responsiveness to acetylcholine were increased in KW29-transferred mice after
      antigen provocation. Both responses were dose-dependently suppressed by the
      administration of dexamethasone or cyclosporin A in vivo. We concluded that
      airway eosinophilic inflammation can be controlled by agents capable of
      downregulating IL-5 production in T cells.

PMID- 9758893
TI  - Heterogeneous expression of tumor necrosis factor-alpha receptors I and II on
      human peripheral eosinophils.
AB  - BACKGROUND: Expression of the tumor necrosis factor-alpha receptor by human
      eosinophils has not been determined. We examined the surface expression and mRNA
      for tumor necrosis factor-alpha receptors I and II (TNF-alphaRI and TNF-alphaRII)
      on peripheral eosinophils. METHODS: Eosinophils were obtained from 17 asthma
      patients and 3 healthy volunteers. Flow cytometry was used to examine receptor
      expression, and the reverse transcriptase-polymerase chain reaction was used to
      examine receptor mRNA expression. RESULTS: Flow cytometry revealed that 16 out of
      20 subjects had eosinophils expressing TNF-alphaRI and 18 subjects had
      eosinophils expressing TNF-alphaRII. All eosinophils expressed at least one
      receptor. The mRNA for TNF-alphaRII was detected in all eosinophils examined, but
      the signals for TNF-alphaRI mRNA were only found in cells expressing this
      receptor. CONCLUSIONS: Human peripheral eosinophils show heterogeneous expression
      of TNF-alphaRI and TNF-alphaRII.

PMID- 9758894
TI  - Altered expression of CD11b and CD62L after cross-linking of CD45 isoforms on
      human eosinophils.
AB  - BACKGROUND: Phosphotyrosine phosphatase CD45 is exclusively found on nucleated
      hematopoietic cells. CD45 is an essential component of signaling of mast cel
      degranulation and of lymphocyte activation, but little is known about its role in
      eosinophils. In the present study, we have determined the expression and function
      of CD45 isoforms on human eosinophils. METHODS: Expression of CD45 isoforms on
      purified peripheral blood eosinophils was examined using indirect
      immunofluorescence and flow cytometry. Eosinophils were cultured with anti-CD45
      isoform monoclonal antibodies (mAbs) for up to 24 h. Eosinophil activation was
      evaluated by measuring surface expression of CD11b or CD62L by flow cytometry.
      RESULTS: Fresh eosinophils express CD45, CD45RB, CD45RO epitopes but not CD45RA.
      Incubation with anti-CD45 isoform mAb for 30 min did not alter the expression of
      either CD11b or CD62L on eosinophils. In contrast, the expression of CD11b was
      significantly enhanced after 24 h of incubation with mAbs against CD45, CD45RB,
      or CD45RO. In addition, the expression of CD62L was also significantly reduced
      with anti-CD45RB and with anti-CD45RO mAbs. CONCLUSIONS: Cross-linking of surface
      CD45 isoforms for 24 h significantly induced upregulation of CD11b expression and
      CD62L shedding, consistent with activation of eosinophils. Our data suggest that
      CD45 isoforms are functionally expressed on human eosinophils, and are capable of
      modulating eosinophil function and might participate in allergic inflammation.

PMID- 9758895
TI  - RANTES augments eosinophil lucigenin-dependent chemiluminescence.
AB  - BACKGROUND: RANTES (regulated on activation, normal T expressed and secreted) has
      been shown to possess chemotactic activity for eosinophils. Eosinophils have been
      considered to play a key role in the allergic inflammation through the release of
      inflammatory molecules such as radical oxygen products. Thus, in this study, we
      examined the effect of RANTES on radical oxygen products from eosinophils.
      METHODS: Eosinophils were isolated from heparinized venous blood of patients with
      bronchial asthma by the modified CD16-negative depletion method. Radical oxygen
      products were examined in terms of lucigenin-dependent chemiluminescence. To a
      mixture of 50 microl of eosinophils (2x10(6)/ml) and 50 microl of lucigenin
      (5x10(-4)M), 50 microl of calcium ionophore A23187 (final concentration 10(-5)M)
      was added, and radical oxygen products were determined for 600 s. RESULTS: RANTES
      treatment resulted in the enhancement of peak value (0.64+/-0.23 RLU) and
      integrated value (119.08+/-20.52 RLU) as compared to untreated cells (0.15+/-0.03
      RLU, 29.48+/-8.92 RLU, respectively). CONCLUSIONS We could conclude that RANTES
      might play an important role in the pathogenesis of allergic inflammation through
      involvement in selective eosinophil infiltration and eosinophil activation by
      augmentation of eosinophil oxidative metabolism.

PMID- 9758896
TI  - Involvement of beta1 and beta2 integrin stimulation in RNA synthesis in an
      eosinophilic cell line (EoL-1).
AB  - In allergic inflammatory disease, especially in bronchial asthma, eosinophils
      play important roles as essential inflammatory cells. In the accumulation of
      eosinophils in airway inflammation, eosinophils receive very diverse stimuli. In
      this study, we investigated the influences of the signal between beta2
      integrin/intercellular adhesion molecule-1 (ICAM-1) or beta1 integrin/fibronectin
      (FN) and RNA synthesis on proteins in eosinophilic cell line-1 (EoL-1), using
      recombinant soluble ICAM-1 (r-sICAM-1) as a global response of eosinophils. 3H
      thymidine incorporation and 3H-uridine incorporation were used as indices for DNA
      synthesis and RNA synthesis, respectively. In a comparison of the RNA/DNA ratio
      with various durations of stimulation of 1 microg/ml of r-sICAM-1 and 100
      microg/ml of FN, a time-dependent increase was observed, but the increase induced
      by FN rose slower than that induced by r-sICAM-1. From this result, a beta2
      integrin/ICAM-1 signal induced an increase in the RNA/DNA ratio in EoL-1,
      implying that the signal promotes RNA synthesis, which suggests that various
      types of protein synthesis, such as the synthesis of various cytokines, are
      induced by the beta2 integrin/ICAM-1 signal. Similar results were obtained with a
      beta1 integrin signal using FN, but there was a difference in the time course
      between beta2 integrin/ICAM-1 and beta1 integrin/FN signals. This experimental
      method may be useful for understanding these manifestations as a global response
      of eosinophils.

PMID- 9758897
TI  - Human skin mast cells produce TNF-alpha by substance P.
AB  - Using in situ hybridization and the reverse transcriptase polymerase chain
      reaction (RT-PCR) we show that messenger RNA for IL-4, IL-5 and tumor necrosis
      factor-alpha (TNF-alpha) is induced by cross-linkage of high-affinity Fc(epsilon)
      receptors (Fc(epsilon)RI) on human skin mast cells, but that only TNF-alpha mRNA
      is selectively induced by substance P. Skin mast cells were purified using the
      Percoll density technique. T cells were removed by serial negative selection
      using a CD2 monoclonal antibody (mAb) to achieve a final mast cell purity >95%.
      Purified mast cells were precultured with recombinant human stem cell factor
      (rhSCF; 10 ng/ml) and myeloma IgE (3 microg/ml) for 16 h before challenge with
      sheep polyclonal antihuman IgE antibody (anti-IgE; 1 or 10 microg/ml) in the
      presence of rhSCF (50 ng/ml). Using in situ hybridization, we demonstrated that
      IgE-dependent stimulation induces the expression of IL-4, IL-5 and TNF-alpha mRNA
      in skin mast cells. We have investigated the expression of IL-4, IL-5 and TNF
      alpha mRNA by substance P, with the result that substance P, 0.003-30 microM,
      selectively induced TNF-alpha mRNA. However, substance P did not induce IL-4 mRNA
      and did not enhance IL-5 mRNA. Furthermore, we confirmed the release of TNF-alpha
      by substance P from skin mast cells using an ELISA technique. These findings
      demonstrate the capacity of human skin mast cells to transcribe IL-4, IL-5 and
      TNF-alpha by immunological activation and to transcribe and release TNF-alpha by
      substance P.

PMID- 9758898
TI  - Eosinophil degranulation in the presence of lung fibroblasts.
AB  - BACKGROUND: Although eosinophils (Eos) and fibroblasts (Fb) are closely
      approximated in the bronchial submucosae of asthmatics, and are believed to play
      important roles in the pathogenesis of bronchial asthma, the interaction between
      Eos and Fb has not been thoroughly elucidated. In this study, we have examined
      eosinophil cationic protein (ECP) release from human Eos cultured in the presence
      of human lung Fb. METHODS: Eos from healthy donors were cultured with or without
      C5a for 16 h in the presence of human fetal lung Fb which had previously been
      incubated with or without some cytokines for 4 h. ECP in supernatants was
      measured by RIA. RESULTS: ECP release was potentiated only when both Eos and Fb
      were activated by C5a and TNF, respectively, while it was not significantly
      potentiated when either Eos or Fb were activated. ECP release from Eos activated
      by C5a was also potentiated when Fb were stimulated by IL-1beta. The enhancement
      of ECP release in cocultured Eos and Fb with stimulation was partly inhibited by
      monoclonal antibodies against GM-CSF and was accompanied by the enhancement of
      adhesion of Eos to Fb. CONCLUSIONS: This study shows that the stimulation of both
      Eos and Fb increases ECP release. It is suggested that Fb may influence Eos
      degranulation and play a role in the pathogenesis of bronchial asthma.

PMID- 9758899
TI  - Human eotaxin induces eosinophil-derived neurotoxin release from normal human
      eosinophils.
AB  - BACKGROUND: Eosinophil granule proteins deposition at the site of allergic
      inflammation contributes to the late-phase reaction of hypersensitivity diseases.
      In the present communication, we describe the effect of human eotaxin on normal
      human eosinophil exocytosis measured as degranulation of eosinophil-derived
      neurotoxin (EDN). METHODS: Purified eosinophils were obtained from normal healthy
      volunteers with the CD16-negative procedure. Purified eosinophils were stimulated
      with various concentrations of eotaxin and the amount of EDN released was
      analysed by radioimmunoassay. Flow cytometry was used to examine the surface
      expression of adhesion molecules on eosinophils. RESULTS: Eotaxin significantly
      induced EDN release in a dose-dependent manner. The potency of eotaxin in this
      effect was equal to that of RANTES, and comparable to that of platelet-activating
      factor. Eotaxin-induced EDN release was blocked by cytochalasin B in a dose
      dependent manner. The surface expression of CD11a, CD11b, CD18 and VLA-4 adhesion
      molecules on normal human eosinophils were not modulated by eotaxin stimulation.
      CONCLUSIONS: These results indicate that eotaxin may play an important role not
      only as a selective chemotaxin for the cell type but also as a secretagogue.
      Furthermore, they demonstrate a degranulation mechanism(s) involving cytoskeletal
      changes which is probably independent of the quantitative expression of adhesion
      molecules.

PMID- 9758901
TI  - Signal transduction in activation of human eosinophils: G protein-dependent and 
      independent pathways.
AB  - Degranulation of eosinophils and subsequent release of toxic granule proteins
      play a key role in allergic diseases such as bronchial asthma. We have previously
      shown that stimulation of eosinophils with immobilized secretory immunoglobulin A
      (sIgA) induced the phosphorylation of several proteins including 51-, 65-, 73-,
      78-, 100-, 105- and 113-kD proteins. Pervanadate, a protein tyrosine phosphatase
      inhibitor, also induced at least 7 tyrosine phosphorylated proteins including
      those observed with immobilized sIgA. Pervanadate also induced inositol phosphate
      (IP) production and degranulation of eosinophils in a concentration-dependent
      manner. Eosinophil production of IP and degranulation as well as tyrosine
      phosphorylation of proteins induced by sIgA were completely inhibited by a
      tyrosine kinase inhibitor, genistein, and pertussis toxin (PTX), suggesting the
      involvement of both the PTX-sensitive guanine nucleotide-binding (G) protein and
      protein tyrosine kinases (PTK) in sIgA-induced activation of eosinophils. In
      contrast, PTX did not affect tyrosine phosphorylation induced by sIgA or
      pervanadate. Furthermore, pervanadate-induced IP production was partially
      inhibited by PTX. Finally, a phospholipase C-gamma2 isoform was tyrosine
      phosphorylated by pervanadate, but not by sIgA. These findings suggest that at
      least two different pathways, i.e. PTK-mediated G protein-dependent or 
      independent PLC activation, are involved in the activation of human eosinophils.

PMID- 9758900
TI  - Suppressive effects of SP-A on ionomycin-induced IL-8 production and release by
      eosinophils.
AB  - Recent studies have demonstrated that pulmonary surfactant protein (SP)-A plays a
      potential role in modifying inflammation and immune function. To see whether SP-A
      could modify IL-8 production and release by eosinophils stimulated with
      ionomycin, SP-A purified from surfactant recovered from patients with alveolar
      proteinosis was added to eosinophils isolated by the negative-selection method
      with immunomagnetic beads, and cultured for 24 h. The concentrations of IL-8 in
      the cell-free supernatants and cell lysates were then measured by ELISA. SP-A
      attenuated the production of IL-8 by eosinophils in a concentration-dependent
      manner. SP-A also attenuated the release of IL-8 from the eosinophils. The
      addition of SP-A antibody (PE10) reversed these effects of SP-A completely. These
      data suggest that SP-A may have the potential to modify allergic inflammation by
      inhibiting the release and production of IL-8 by eosinophils.

PMID- 9758902
TI  - Cross-linking of the beta2 integrin, CD11b/CD18, on human eosinophils induces
      protein tyrosine phosphorylation and cellular degranulation.
AB  - Adhesion molecules, including integrins, play an important role in the selective
      recruitment of eosinophils. It has recently been shown that integrins also
      modulate the functions of eosinophils. Here, we tested the hypothesis that cross
      linking of the beta2 integrin, alphaMbeta2Mac-/, leads to intracellular signaling
      events such as activation of protein tyrosine kinases leading to eosinophil
      degranulation. Cross-of cell surface CD11b/with anti-tibody and goat anti-G
      immobilized onto the plate triggered tyrosine phosphorylation of several
      intracellular proteins, including the one with a 115-kD mass (pp115). The same
      stimulus also provoked degranulation of eosinophils. These findings suggest that
      engagement of beta2 integrin on eosinophils triggers the activation of
      intracellular signaling cascade which leads to cellular degranulation.

PMID- 9758903
TI  - Interferon-gamma receptor beta-chain expression and formation of alpha- and beta
      chain complexes after receptor conjugation on human peripheral eosinophils.
AB  - BACKGROUND: It has been unclear whether or not the interferon-gamma receptor (IFN
      gammaR) on human peripheral eosinophils is completely functional. Accordingly, we
      examined the expression of IFN-gammaR alpha- and beta-chains and the association
      of the two chains after binding of IFN-gamma to the receptor. METHODS: Peripheral
      blood eosinophils were obtained from 8 patients (bronchial asthma, n=6, and
      hypereosinophilic syndrome, n=2), and expression of the alpha- and beta-chain was
      investigated by flow cytometry with specific antibodies. Expression of mRNA for
      the alpha- and beta-subunits was also investigated by the reverse transcriptase
      polymerase chain reaction. RESULTS: Eosinophils from all the patients were
      positive for both the alpha- and beta-chains by flow cytometry. In addition, mRNA
      for both chains was detected by the polymerase chain reaction. Furthermore,
      coprecipitation of the alpha- and beta-chains was only found after eosinophil
      stimulation with IFN-gamma. CONCLUSIONS: Human peripheral eosinophils apparently
      express both the alpha- and beta-chains of the IFN-gammaR, and the two chains may
      only form the receptor complex after ligand binding.

PMID- 9758904
TI  - Whole-blood flow-cytometric analysis of eosinophil EG2 expression as a marker of
      the pathological conditions of asthma.
AB  - Using a simple technique detecting the eosinophil fraction in whole-blood flow
      cytometry, we measured intracellular antigen EG2 (a monoclonal antibody to
      eosinophil cationic protein) in 56 asthmatic patients (26 during an attack and 30
      during an asymptomatic period) and 22 healthy subjects to determine whether EG2
      reflects the pathological stages of allergy. METHODS: In brief, preparations of
      the sample included the following procedures: (1) hemolyzation of heparinized or
      EDTA-mixed whole blood; (2) fixation of white blood cells with 0.4%
      parabenzoquinone (PBQ) or paraformaldehyde (PFA); (3) permeabilizing the cell
      membrane with n-octyl-beta-D-glucopyranoside, and (4) staining of intracellular
      EG2 antigen with monoclonal EG2 antibody and FITC-labeled secondary antibody.
      RESULTS: In PBQ-fixed samples, there was a clearer boundary of the eosinophil
      fraction with a higher yield and purity than in those fixed with PFA. The number
      of EG2-positive eosinophils was significantly greater in subjects during attacks
      than in asymptomatic patients. In addition, when compared with normal controls,
      asthmatic subjects had significantly greater numbers of EG2-positive eosinophils
      regardless of their current condition. CONCLUSION: Eosinophil intracellular EG2
      may indicate the pathological stage of asthma. This simple technique for
      analysing the properties of eosinophils using whole-blood flow cytometry would
      save time and labor in laboratories.

PMID- 9758905
TI  - Glutamatergic neurotransmission in alcoholism.

PMID- 9758906
TI  - HLA-E is the ligand for the natural killer cell CD94/NKG2 receptors.

PMID- 9758907
TI  - The radiation-sensitive costimulatory factors involved in B-cell-dependent T-cell
      activation by minor lymphocyte stimulating antigen.

PMID- 9758908
TI  - A novel regulator inhibits HBV gene expression.

PMID- 9758909
TI  - Patterns of circulating hepatitis B surface antigen variants among vaccinated
      children born to hepatitis B surface antigen carrier and non-carrier mothers. A
      population-based comparative study.

PMID- 9758910
TI  - Quantitative examination of the cardiac myocytes in hypertensive rats under
      chronic inhibition of nitric oxide synthesis.

PMID- 9758911
TI  - Characterization of a phage specific to hemorrhagic Escherichia coli O157:H7 and
      disclosure of variations in host outer membrane protein ompC.

PMID- 9758954
TI  - Physiologically relevant one-compartment pharmacokinetic models for skin. 1.
      Development Of models 

PMID- 9758955
TI  - The capitation debate.

PMID- 9758912
TI  - Retroviral transfer of antisense sequences results in reduction of C-Abl and
      induction of apoptosis in hemopoietic cells.

PMID- 9758956
TI  - Issues to consider in dental managed care programs.

PMID- 9758957
TI  - Blood-filled spaces with and without filler materials in guided bone
      regeneration. A comparative experimental study in the rabbit using bioresorbable
      membranes.
AB  - The aim of the present study was to evaluate the effect of natural deproteinized
      bone mineral on the temporal and spatial pattern of bone formation in a guided
      bone regeneration model system while using a bioresorbable membrane device. A
      periosteal skin flap was raised uncovering the calvaria of 20 rabbits. A stiff
      hemispherical dome made of polylactic acid was placed onto the roughened calvaria
      and anchored by screws. Prior to placement, the dome was either filled with
      peripheral blood (control group, 8 rabbits) or with blood and OsteoGraf/N-300
      (test group, 12 rabbits). At 1 month, histologic sections revealed bone
      regeneration in both test and control domes to various degrees. In the test
      domes, bone height reached 78% (67-83) and bone volume was 11% (6-17), while in
      the control domes, bone height was 45% (14-67) and bone volume 6% (1-11). At 2
      months, bone height was unchanged in the test group at 70% (67-83) and bone
      volume had only slightly increased to 16% (11-21). In the controls, height
      increased to 86% (60-100) and volume to 20% (9-27). Thus, in this model system,
      natural bone mineral fill contributed to accelerate initial bone neogenesis,
      while it did not contribute to increasing bone volume or bone height at later
      observation stages.

PMID- 9758958
TI  - Bone augmentation at titanium implants using autologous bone grafts and a
      bioresorbable barrier. An experimental study in the rabbit tibia.
AB  - The aim of the present investigation was to compare the effect of using
      autologous bone particles covered with a bioresorbable matrix barrier with the
      use of bone particles alone on bone augmentation at titanium implants installed
      in the rabbit tibia. Two Branemark System implants, one in each tibia, were
      inserted in each of 9 rabbits in such a way that 5 threads were not covered with
      bone. Autologous bone particles were harvested from the skull and placed over the
      exposed implant surfaces on each tibia. The bone graft on one tibia was covered
      with a Guidor Matrix Barrier, while the bone graft on the other tibia served as a
      control. After a healing period of 12 weeks, the animals were sacrificed and
      specimens taken for histomorphometrical analyses. The analyses showed that a
      significantly larger volume of augmented bone tissue had formed at the test
      sites. There were, however, no differences in the amount of mineralized bone. In
      fact, the difference in tissue volume was due to an increased amount of bone
      marrow at the test sites. The degree of mineralized bone to implant contact as
      well as the degree of mineralized bone within the threads at the test implants
      were similar to that at the controls. In conclusion, it was found that the
      coverage of particulate autologous bone grafts with a bioresorbable barrier
      resulted in a larger volume of augmented bone than the use of bone grafts not
      covered with a barrier.

PMID- 9758959
TI  - Augmentation of skull bone using a bioresorbable barrier supported by autologous
      bone grafts. An intra-individual study in the rabbit.
AB  - The aim of this experimental investigation was to compare the effect of using
      autologous particulate bone grafts with and without a bioresorbable barrier
      covering for augmentation of the rabbit skull bone. For this purpose, bilateral,
      circular, 8 mm wide and 1 mm deep skull bone defects were prepared and overfilled
      with particulate bone grafts. The grafts placed in the test sites were covered
      with a bioresorbable barrier (Guidor Matrix Barrier). The grafts placed in the
      control sites were covered only by the repositioned, cutaneous flap. 12 weeks
      later, the animals were sacrificed, the experimental sites were defleshed and the
      height and volume of the augmented bone in the test and control sites were
      measured clinically. Histologically, morphometrical measurements of the bone
      tissue were performed in decalcified vertical cross-sections of the experimental
      sites. Statistically significant differences were found in favour of the coverage
      of the bone graft particles with the barrier, both with respect to the height and
      the volume of the augmented bone.

PMID- 9758960
TI  - Bioactive glass and calcium carbonate granules as filler material around titanium
      and bioactive glass implants in the medullar space of the rabbit tibia.
AB  - The effect of bioactive glass (BG) and calcium carbonate (CC) granules on bone
      formation around titanium and BG implants projecting into the medullary space of
      rabbit tibia was studied. The bone marrow tissue was removed and the medullary
      space was filled either with BG or CC (Biocoral) granules (phi 630-800 microns).
      Conical titanium and BG implants were inserted into the holes drilled in compact
      bone using the press fit-technique. Histomorphometry was used to measure the bone
      biomaterial area in a 1.0 mm wide zone around the head of the implant and the
      contact between formed bone and implant. Significantly larger bone-biomaterial
      area was obtained around titanium implants using BG than CC granules while no
      difference was found in connection of BG implants. Better bone-implant contact
      was achieved with BG implants than with titanium implants regardless of the type
      of granules used. The results indicate that BG may prove to be useful as filler
      and coating material in connection of implants projecting into bone cavities.

PMID- 9758961
TI  - Morphological and dimensional changes after barrier removal in bone formed beyond
      the skeletal borders at titanium implants. A kinetic study in the rabbit tibia.
AB  - The aim of the present experimental investigation was to study the morphological
      and dimensional changes of bone, augmented at titanium implants by a membrane
      technique, taking place after membrane removal. In 12 rabbits, screw-shaped
      titanium implants were inserted in the tibial metaphyses in such a way that 5
      threads became uncovered with bone. Surgery was performed on 2 occasions in order
      to retrieve specimens with different follow-up times. An e-PTFE barrier and a
      titanium device were used to provide space for bone formation. In 1 tibia of each
      rabbit, the membranes and spacers were removed after 8 weeks of healing, and the
      implants followed for 16 more weeks. Impressions were taken at day 0 and after 8
      and 24 weeks of healing and plaster models were produced. In the contralateral
      tibiae, implants were inserted either 16 or 8 weeks prior to sacrifice.
      Measurements were made on the plaster models in 3 dimensions at 35 points around
      each implant in a coordinate measuring machine. Specimens taken 8, 16 and 24
      weeks after insertion were analysed by means of light microscopical morphometry.
      The coordinate measurements showed that, in mean, 1.92 mm of bone had been formed
      during the first 8 weeks. A statistically significant loss of the height of the
      newly formed bone (0.70 mm) and thereby reduction of bone volume was found 24
      weeks postoperatively. The volume decrease of the newly formed bone was more
      pronounced beside the implants than over the implant body. The histology showed
      that woven bone had been formed at the implants after 8 weeks. Further bone
      formation and remodelling and a net increase of mineralized bone were seen. The
      degree of bone-implant contact and bone area in the threads increased with time.
      The present study showed that coordinate measurements on plaster models, obtained
      from the experimental areas, in combination with histology, form a useful
      technique to study long-term changes of augmented bone. It was found that bone
      formed by a barrier membrane technique, decreased in volume during a 16-week
      follow-up period after barrier removal. Less dimensional changes were observed
      for the bone formed over the implant body, indicating that a solid surface may
      have a stabilizing effect on the augmented bone.

PMID- 9758962
TI  - Healing around implants placed in bone defects treated with Bio-Oss. An
      experimental study in the dog.
AB  - The aim of the present experiment was to (i) study the healing after 3 and 7
      months of bone defects filled with cancellous bovine bone mineral and (ii)
      compare the healing around implants placed in normal bone and in defects filled
      with bovine bone mineral. 5 beagle dogs, about 1-year-old, were used. At
      baseline, extractions of all mandibular left and right premolars were performed.
      Bone defects were prepared in the left mandibular quadrant. The defect was
      immediately filled with natural bovine cancellous bone mineral particles (Bio
      Oss, Geistlich Sons Ltd. Wolhusen, Switzerland). No resective surgery was
      performed in the right jaw quadrant. In both quadrants the flaps were adjusted to
      allow full coverage of the edentulous ridge and sutured. 3 months later, 2 dogs
      (group I) were euthanized and biopsies from the premolar regions obtained and
      prepared for histologic analysis. The 3 remaining dogs (group II) were at this
      time interval (3 months) subjected to implant installation in the premolar region
      of both the right and left mandibular jaw quadrants. 2 fixtures of the ITI Dental
      Implant System (Straumann, Waldenburg, Switzerland; solid-screw; 8 x 3.3 mm) were
      installed in each side. The fixtures in the test side were placed within the
      previously grafted defect area, while the fixtures in the control side were
      placed in normally healed extraction sites. A 4 month period of plaque control
      was initiated. At the end of this period, a clinical examination including
      assessment of plaque and soft tissue inflammation was performed and radiographs
      obtained from the implant sites. Biopsies were harvested and 4 tissue samples
      were yielded per dog, each including the implant and the surrounding soft and
      hard peri-implant tissues. The biopsies were processed for ground sectioning or
      "fracture technique" and the sections produced were subjected to histological
      examination. The volume of the hard tissue that was occupied by clearly
      identified Bio-Oss particles was reduced between the 3- and 7-month intervals.
      This indicates that with time, Bio-Oss becomes integrated and subsequently
      replaced by newly formed bone. In other words, this xenograft fulfils the
      criteria of an osteoconductive material. It was also observed that 4 months after
      implant installation, the titanium/hard tissue interface at test and control
      sites exhibited, from both a quantitative and qualitative aspect, a similar
      degree of "osseointegration".

PMID- 9758963
TI  - Characteristics of the cancellous bone of edentulous mandibles.
AB  - Trabecular bone volume and trabecular connectivity (trabecular bone pattern
      factor) of edentulous mandibles were examined using undecalcified bone sections
      from the region of the 1st premolar to investigate atrophy-related changes in
      mandibular cancellous bone. The mean trabecular bone volume was 21.8% in female
      mandibles and 36.6% in male mandibles. The mean trabecular bone pattern factor
      was -0.22 mm-1 for female mandibles and -2.29 mm-1 for male mandibles. The
      difference between the sexes was statistically conspicuous for both parameters,
      but did not attain statistical significance. A notable fact was the extreme range
      of variation in both trabecular bone volume and trabecular connectedness. A
      difference of 65% between the highest and the lowest trabecular bone volumes
      measured in the present study (min, 7.6%; max, 73.6%, both male) reflects the
      possible variation in trabecular density of edentulous mandibles.

PMID- 9758964
TI  - Orthodontic anchorage capacity of short titanium screw implants in the maxilla.
      An experimental study in the dog.
AB  - The aim of this study was to investigate experimentally the effect of long term
      orthodontic loading on the stability as well as on the peri-implant bone findings
      of short titanium screw implants (Bonefit, submersion depth 6 mm, phi 4 mm)
      inserted in regions with reduced vertical bone height. For this purpose, 6
      maxillary premolars (1P1, 2P2, 3P3) were extracted from each of 2 foxhounds and
      reduction of alveolar bone height was performed by osteotomy. After a 16-week
      healing period, 8 implants (4 per dog) were inserted in the edentulous areas.
      Simultaneously, 2 implants (1 per dog) were positioned in the palatal suture (one
      stage surgery). After an 8-week implant healing period, the fixtures in the P1/P2
      areas (n = 4) and the palate (n = 2) were loaded (test implants) by means of
      transpalatal bars running anteriorly, fixed on the implants in the P1/P2 areas,
      and Sentalloy traction springs (approximately 2 N continuous force) inserted
      midsagittally between palatal implants and bars (force application period: 26
      weeks). The fixtures in the P2/P3 areas served as controls (n = 4). Clinical
      measurements and histological evaluation revealed no implant dislocation of the
      loaded fixtures. These results suggest that short titanium screw implants
      inserted in the alveolar bone and palatal suture region retain their stability
      during long-term orthodontic loading, even following a relatively short unloaded
      implant healing period. Furthermore, it seems that long-term orthodontic loading
      may induce marginal bone apposition adjacent to the implants.

PMID- 9758965
TI  - Force distribution on implants supporting overdentures: the effect of distal bar
      extensions. A 3-D in vivo study.
AB  - Force distribution on mandibular implants supporting overdentures was registered
      in vivo by means of piezo-electric transducers that allow for simultaneous force
      measurements in 3 dimensions. The anchorage device for connecting the overdenture
      to the implants was a U-shaped bar to which distal extensions were soldered
      bilaterally. Force patterns were analyzed under different test conditions such as
      maximum force when biting in centric occlusion, maximum biting with the
      unilateral use of a bite plate, parafunction and chewing bread. Maximum force
      measured in centric occlusion and on the ipsilateral implant with the use of bite
      plate was increased in the vertical dimension, compared to transverse dimensions.
      On the contralateral implant, equally low values were found, in all 3 dimensions.
      Transverse force components reached 5 to 35% of the vertical magnitudes. With the
      use of the bite plate on the ipsilateral implant, force magnitudes in the
      vertical direction and in the backward-forward direction were significantly
      higher (P < 0.01, P < 0.00) compared to measurements in centric occlusion.
      Chewing and grinding resulted in lower vertical forces compared to maximum
      biting, while transverse forces in the backward forward direction reached force
      magnitudes that resembled the vertical component (50 to 100%). The prevalent (>
      95%) or exclusive force direction in the vertical dimension, registered on both
      implants was downward. However, with the unilateral use of the bite plate, upward
      directions were found on the contralateral implant as an effect of distal bar
      extensions. This was in contrast to previous results where upward force
      directions were not found. In transverse dimensions, the specific influence of
      bar extensions was recognised in backward directions on the contralateral
      implant. In comparison with previous results, it was concluded that, in vivo, the
      effect of distal bar extensions was of much lesser influence regarding force
      magnitudes and force directions than was expected.

PMID- 9758966
TI  - Polymerization contraction stress in thin resin composite layers as a function of
      layer thickness.
AB  - OBJECTIVES: In the present study, the effect of layer thickness on the curing
      stress in thin resin composite layers was investigated. Since the value of the
      contraction stress is dependent on the compliance of the measuring equipment
      (especially for thin films), a method to determine the compliance of the test
      apparatus was tested. METHODS: A chemically initiated resin composite (Clearfil
      F2, Kuraray) was inserted between two sandblasted and silane-coated stainless
      steel discs in a tensilometer. The curing contraction of the cylindrical samples
      was continuously counteracted by feedback displacement of the tensilometer
      crosshead, and the curing stress development was registered. After 20 min, the
      samples were loaded in tension until fracture. The curing stress was determined
      for layer thicknesses of 50, 100, 200, 300, 400, 500, 600, 700 microns, 1.4 mm
      and 2.7 mm. The compliance of the apparatus was calculated with the aid of a non
      linear regression analysis, using an equation derived from Hooke's Law as the
      model. RESULTS: None of the samples fractured due to contraction stress prior to
      tensile loading. The contraction stress after 20 min decreased from 23.3 +/- 5.3
      MPa for the 50 microns layer to 5.5 +/- 0.6 MPa for the 2.7 mm layer. The
      compliance on the apparatus was 0.029 mm/MPa. SIGNIFICANCE: A measuring method
      was developed which was found to be suitable for the determination of axial
      polymerization contraction stress in this films of chemically initiated resin
      composites. The method makes it possible to estimate the stress levels that occur
      in resin composite films in the clinical situation.

PMID- 9758967
TI  - Fracture toughness and load relaxation of dentin bonding resin systems.
AB  - OBJECTIVES: The fracture toughness (KIC) and load relaxation of four dentin
      bonding resins were determined to characterize some of the mechanical properties
      of these materials after polymerization. METHODS: A total of 40 single-edge notch
      bar specimens were fabricated, 10 each of four commercially available brands, and
      subjected to three-point bending until fracture, as described in ASTM Standard
      E399-83 (1991a). The critical stress intensification factor, KIC, was derived for
      each specimen and compared by analysis of variance and Scheffe's multiple
      comparisons test (p < 0.01). To study the load relaxation characteristics, five
      rectangular specimens (without notches) of each brand were subjected to three
      point loading until a predetermined limiting load value was reached. The test
      load was allowed to relax for 4 min, after which the specimen was unloaded to the
      zero load condition, and the load was allowed to build up on its own accord for 3
      min. Load relaxation values were measured from the chart, and the mean percent
      load drop was calculated. The load relaxation data were compared using analysis
      of variance and Scheffe's multiple comparisons test (p < 0.05). RESULTS: The
      fracture toughness (KIC) values of the four adhesive resins studied in this
      investigation ranged from 0.37-0.94 MPa.m0.5 and were statistically different
      from each other (p < 0.001). The load relaxation values were found to be greatest
      within the first 0.5 min, with the total load relaxation of the four bonding
      agents ranging from 16%-30%. Two of the materials studied showed significantly
      different short-term load relaxation behavior than the other two resins (p <
      0.05). SIGNIFICANCE: Bonding agents can be implicated as one of the factors that
      weaken the interface between the dentin and the composite restorative material.
      These materials are capable of a rapid short-term response, demonstrating
      significant load relaxation in the first 0.5 min after loading.

PMID- 9758969
TI  - Surface analysis of nickel-titanium archwire used in vivo.
AB  - OBJECTIVES: The surface quality of an archwire is a critical factor in the
      prevention of corrosion. This study was conducted to evaluate and assess the
      surface of as-received and used nickel-titanium archwires for evidence of
      corrosion, and to analyze possible corrosion products. METHODS: Round 0.4 mm and
      square 0.4 mm x 0.55 mm nickel-titanium archwires from two manufacturers were
      subjected to elemental analysis, examined, and photographed in a scanning
      electron microscope with an EDAX unit. The used wires had been in service from 3
      wk to 4 mon. There were no systematic differences in surface topography or
      composition between the as-received and used wires. RESULTS: The examination
      revealed undulated surfaces with manufactural scratches and crevices. The surface
      quality within the same archwire varied slightly, with different smoothness in
      the anterior and posterior regions. No systematic discernible difference was
      found between used and as-received arch wires. The analyses of different areas on
      the used archwires revealed no differences in the metal composition.
      SIGNIFICANCE: The surface defects found on the as-received wires were evidently
      not large enough to act as sites for corrosion attack.

PMID- 9758968
TI  - Resistance of cementum in Class II and V cavities to penetration by an adhesive
      system.
AB  - OBJECTIVES: As the cervical margin located in cementum-dentin is still the most
      unpredictable area of an adhesive resin restoration, the aim of this
      investigation was to evaluate the morphology of the cementum layer at the
      cervical margins of Class V and Class II cavities and the impregnability of this
      layer to resin bonding systems. METHODS: Three different types of in vitro
      investigations of the cervical margins were performed by scanning electron
      microscopy: 1) direct anatomical observation of conditioned cavities; 2)
      observation of resin replicas; and 3) observation of resin infiltration. During
      direct observation, the presence of opened tubules was evaluated; in the resin
      replicas, the presence of resin tags and their density were observed; in the
      observation of resin infiltration, the presence of an acid-resistant
      interdiffusion was investigated. RESULTS: From direct observation, cut tubules
      were seen 200 microns from the cervical margin. After treatment with a dentin
      bonding system, the outer layer was infiltrated by the resin. In the resin
      replica, the presence of resin tags was detectable 150-200 microns from the
      margin. In Class II samples, the presence of an outer layer at the cervical
      margin, which could not be identified as bulk dentin or cementum, was clearly
      detectable by both direct and indirect observation. In the Class V samples, the
      border between this layer and bulk dentin was less evident. SIGNIFICANCE: The
      presence of a cementum layer of approximately 150-200 microns at the cervical
      margins of cavities may pose a serious clinical problem for reliable bonding.
      Although in the present study the observation of a zone of resin-impregnated
      cementum may confirm the improvement obtained with the last generation of
      hybridizing dentin bonding systems, the effectiveness of the bond is still
      unclear.

PMID- 9758970
TI  - In vitro cytotoxicity of amalgams made with binary Hg-In liquid alloys.
AB  - OBJECTIVE: Mercury vapor release from amalgams during setting significantly
      decreases when the amalgams are prepared with binary Hg-In liquid alloys. The
      objective of this study was to compare the cytotoxicity of amalgams made with
      experimental Hg-In alloys with that of amalgam without In and a commercial In
      containing amalgam. METHODS: Amalgam specimens were prepared by triturating a
      high-Cu alloy powder (Tytin, Kerr) with pure Hg or Hg-In liquid alloy containing
      5, 20 or 50% In and also by triturating an In-containing high-copper alloy powder
      (Indiloy, Shofu) with pure Hg. After the specimens were aged for 2 wk, a
      cylindrical specimen of each amalgam was immersed consecutively in cell culture
      medium for 0-8, 8-48 and 48-72 h. The cytotoxicity of the extracts was determined
      by placing them in contact with Balb/c 3T3 mouse fibroblasts for 24 h, after
      which the succinic dehydrogenase (SDH) activity was measured and expressed as a
      percentage of the Teflon negative controls. The results were statistically
      compared using ANOVA and Tukey's test (alpha = 0.05). The concentration of
      elements released into the extracts was determined by atomic absorption
      spectrophotometry and evaluated by Kruskal-Wallis and nonparametric multiple
      comparisons. RESULTS: For the 0-8 h and 8-48 h intervals, the 20% In amalgam was
      significantly (p < 0.05) less toxic than the other amalgams, and not different
      from the Teflon control. Results for the other amalgams were only slightly
      depressed compared to the Teflon control. For the 48-72 h interval, all amalgams
      were essentially no different from the control. Copper was the element dominantly
      released into the medium from all the amalgams tested. SIGNIFICANCE: For amalgam
      tested after aging, alloying indium to mercury did not deleteriously affect the
      cytotoxicity of the resultant amalgam compared to the amalgam without indium.

PMID- 9758971
TI  - Coating of silicone-based impression materials in a glow-discharge system by
      acrylic acid plasma.
AB  - OBJECTIVES: The main purpose of this study was to demonstrate an increase in the
      wettability of silicone-based impression materials after coating them with a
      hydrophilic film in a glow-discharge system. METHODS: Two vinyl polysiloxane
      impression materials, Extrude (Kerr) and Accuflex (GC America Inc.) were used.
      Impression specimens were treated in a glow-discharge reactor at a radio
      frequency of 13.56 MHz at different discharge powers (5-20 W) and exposure times
      (5-60 min). Surface analysis of the specimens was done by FTIR. Surface contact
      angles were obtained by a captive-bubble method. These results were analyzed by
      ANOVA and Duncan's Multiple Range test (p < 0.05). The total number of voids on
      the die stone casts was observed microscopically. Linear dimensional accuracy,
      detail reproducibility, and surface hardness of the die stone casts were also
      determined. A Student t-test was performed for statistical analysis of these
      parameters (p > 0.05). RESULTS: FTIR spectra indicated that the number of
      hydroxyl groups on the surfaces increased (p > 0.05) because of the glow
      discharge treatment. Contact angle measurements showed an increase (p < 0.05) in
      surface hydrophilicity. Total void formation in the stone casts decreased. There
      were no significant differences in the linear dimensional accuracy, detail
      reproducibility, and hardness, before and after glow-discharge treatment (p >
      0.05). SIGNIFICANCE: It was concluded that the surface wettability of the
      impression materials may be increased by plasma deposition, and therefore, the
      formation of voids was reduced in the stone casts.

PMID- 9758972
TI  - Color distribution of three regions of extracted human teeth.
AB  - OBJECTIVES: Knowledge of human tooth color and its distribution are critical to
      the understanding of shade matching in esthetic dentistry. The color of human
      teeth shows a gradation from the gingival to the incisal region. There have been
      many reports in the literature on the distribution of color in teeth, but not in
      the CIE 1976 L*a*b* system. This study was conducted to determine the color
      distribution in three regions in a sample of human teeth and express the results
      in Munsell notation, CIE 1976 L*a*b* and CIE delta E* color differences. The
      hypothesis of this research was that it is possible to detect significant
      differences in the color parameters of the three distinct regions in teeth.
      METHODS: All of the teeth used in this study were extracted, cleaned and stored
      in artificial saliva. Prior to measurement, the teeth were removed from the
      solution and mounted in a holder to ensure consistent measurements. Spectral data
      were collected using a GE recording spectrophotometer, CIE chromaticity
      coordinates calculated using CIE illuminant C and 1931 observer data, and
      conversions made to L*, a*, b* and Munsell notation. The results were analyzed by
      ANOVA and Scheffe's multiple comparisons test. RESULTS: The mean L*, a*, b*s were
      72.6, 1.5, 18.4 for gingival, 72.4, 1.2, 16.2 for middle, and 71.4, 0.9, 12.8 for
      incisal. Average Munsell parameters were 1.2 Y 7.1/2.7 for gingival, 1.3 Y
      7.1/2.4 for middle, and 1.4 Y 7.0/1.9 for incisal. The mean CIE delta E* between
      the gingival and incisal regions of the 95 teeth showed a clinically significant
      difference of 8.2. SIGNIFICANCE: The distribution of color was identified for
      three regions of the tooth. A statistical analysis determined that there are
      statistically significant color differences between the regions, and these
      differences are also clinically significant. This information is beneficial when
      esthetic restorations are required.

PMID- 9758973
TI  - The determination of working time and gelation time of temporary soft lining
      materials.
AB  - OBJECTIVE: The purpose of this study was to establish a new method for the
      determination of working time and gelation time of temporary soft lining
      materials using a displacement rheometer. METHOD: A displacement rheometer (The
      Dental School, University of Newcastle, Newcastle upon Tyne, UK) was used to
      apply a rapid displacement of 0.25 mm held for 1 s at intervals of 60 s to
      samples of four temporary soft lining materials. Material displacement and
      elastic recovery at each test time was recorded. The test procedure was repeated
      three times at 23 degrees C and at 37 degrees C for each material. For one
      material, the displacement time was varied (1, 5, 10 s). The working time was
      defined as the time corresponding to the initial observation of elastic recovery
      at 23 degrees C. Gelation time was the time when a material achieved 95% of its
      maximum elastic recovery at 37 degrees C. Values were compared between materials
      using one-way analysis of variance and Student-Newman-Keuls test at the 5% level
      of significance. RESULTS: The gelation rate of all materials increased with
      increasing temperature although the extent of this influence varied between
      materials. The development of elastic recovery in the materials during gelation
      accurately fitted asymmetric sigmoids. The correlation coefficient (r) ranged
      from 0.982 to 0.999. Statistically significant variations in both the working and
      gelation times of the test materials were established. The time of displacement
      affected both the rate of development of elasticity and the value of elastic
      recovery but this effect was only statistically significant when the displacement
      time was increased to 10 s. SIGNIFICANCE: The displacement rheometer may be
      suited for use as a standard test method for the determination of the working
      time, gelation time and elastic behavior of temporary soft lining materials.

PMID- 9758974
TI  - SEM analysis of marginal expansion and gap formation in Class II composite
      restorations.
AB  - OBJECTIVES: Morphological changes in terms of marginal expansion have been
      observed at the dentin-composite interface of resin composite restorations with
      the scanning electron microscope (SEM), which could not be described with the
      criteria conventionally used for quantitative marginal analysis. The purpose of
      the present study was to elucidate the influence of marginal expansion upon
      marginal integrity and clarify the cause of these morphological changes. METHODS:
      A total of 22 extracted human molars were restored with Class II resin composite
      restorations, with and without the use of a dentin bonding agent. The cervical
      restoration margin was located below the cemento-enamel-junction (CEJ). The
      marginal adaptation at the dentin- and enamel-composite interfaces was evaluated
      and measured on replicas using quantitative SEM analysis after different storage
      periods. The chemical composition of the marginal expansion was determined
      qualitatively by EDX (Energy Dispersive X-Ray) analysis using original tooth
      samples. The results obtained from quantitative SEM analysis were statistically
      analyzed by applying the Mann-Whitney U-test and the error rates method. RESULTS:
      Significantly less marginal expansion occurred at the enamel interface than at
      the dentin-composite interface (p < or = 0.01). Within the dentin, less marginal
      expansion was observed with the use of a dentin bonding agent than without a
      dentin bonding agent (p < or = 0.05). At 1 y, a significant (p < or = 0.05)
      decrease in marginal expansion was observed in both groups. EDX analysis revealed
      that the chemical composition of the marginal expansion is comparable to the
      resin composite, since peaks for silicon, barium and ytterbium could be found at
      these sites. SIGNIFICANCE: In Class II resin composite restorations below the
      CEJ, partial disruption of the adhesive bond may occur initially when curing the
      restoration. Water sorption causes gap reduction by hygroscopic expansion, seen
      in the SEM as a volume increase. Thus, the observed morphological changes can be
      regarded as an early sign of insufficient adhesion between composite and dentin
      at sites where disruption of the bond occurred initially, whether or not a dentin
      bonding agent was used.

PMID- 9758975
TI  - Fracture studies of selected dental restorative composites.
AB  - OBJECTIVES: The purpose of this study was to evaluate the flexure strength,
      elastic modulus, and fracture toughness (mode I, mode II, and mixed mode) of
      resin and four specially made dental restorative composite materials. METHODS:
      Testing was done on prismatic bars in flexure and disk specimens in diametral
      compression. Fracture strengths were analyzed using Weibull statistics.
      Statistical analysis consisted of a one-way analysis of variance followed by a
      Tukey multiple means analysis for each of the materials. In addition, the
      fracture strengths were analyzed using Weibull statistics due to the brittle
      behavior exhibited by these materials. RESULTS: The experimental results showed
      that the addition of fillers resulted in a significant three-fold increase in
      flexure modulus and a significant 30-50% increase in fracture toughness from the
      resin. As was indicated by the different Weibull modulus values, strength data
      obtained from four-point bending were not related with strength data from three
      point bending. A straight notch vs. a relatively sharp V-notch gave higher
      fracture toughness values. Fracture toughness was dependent on the depth of a
      straight notch and was practically independent of the V-notch depth. Mode I and
      II fracture toughness in two composites (75Sr and 75Sr10) were carried out on
      precracked disk specimens in diametral compression. The results of mode I
      toughness were close to those obtained from the flexure testing. The mode II
      toughness values were greater than the mode I values by more than 30%. The data
      fit an equation of the form KI/KIC + (KII/KIIC)2 = 1(where KI, KII are the mode I
      and II stress intensity factors and KIC, KIIC are the respective critical
      values). SIGNIFICANCE: Notching technique, testing configuration (three-point vs.
      four-point loading), and method of testing (bar vs. disk) have significant effect
      on the fracture properties.

PMID- 9758976
TI  - In vivo changes in roughness of resin-modified glass ionomer materials.
AB  - OBJECTIVES: The clinical changes in roughness of resin-modified glass ionomer
      materials is relatively unknown. This study examined the in vivo wear of these
      materials using surface roughness as an indicator of wear patterns. METHODS: Ten
      patients with four cervical abrasion lesions each were selected. The four
      cavities in each patient were restored with Fuji II LC (GC Corp., Japan),
      Vitremer (3M Dental, USA), Photac-Fil (ESPE, Germany) and Fuji Cap II (GC Corp.,
      Japan). After light-curing, the restorations were polished and left uncoated.
      Silicone impressions were made of the surface of each restoration after
      polishing, and then at 3 monthly intervals up to 24 mon after restoration
      placement. Gold-coated resin replicas were made from the impressions for surface
      wear evaluation. Quantitative assessment of wear was performed by measuring
      surface roughness with a confocal microscope for topographical reconstruction of
      the specimen surface. The effect of material at each time period was analyzed
      using the Kruskal-Wallis test with exact non-parametric inference. Rugosity, as
      determined by the center line average, was determined by image analysis. SEM
      images of the same surfaces provided the qualitative analysis. RESULTS: All
      restorations showed a cyclic distribution of rugosity with time as demonstrated
      by lowess plots. There were significant differences between materials at 6, 9 and
      18 mon. The rugosity curves appeared to converge at 24 mon. SIGNIFICANCE: It was
      concluded that the in vivo surface changes in roughness of resin-modified glass
      ionomer materials is cyclic in nature over the first 2 y.

PMID- 9758978
TI  - Ethics and insurance consultants.
AB  - Health care professionals who serve as consultants for insurance companies
      provide an essential service in reducing health care costs and ensuring access to
      care for increased numbers of people. The role and function of these consultants
      is not always appreciated or welcomed by providers, who may view them as
      intruders to the doctor-patient relationship and feel that treatment plans are
      being second-guessed. Consultants, on the other hand, may be placed in
      uncomfortable positions when radiographically visible pathological conditions are
      not addressed on a treatment plan. Overlooking such conditions in hopes of not
      embarrassing the treating dentist is not an ethical option. When an isolated
      omission or error is encountered, it is best for consultants to contact the
      treating dentist and advise him or her of the disparity between planned treatment
      and observed pathology. Patients, providers, and the profession will benefit
      through this collegial exchange of information. When consultants observe
      continual omissions or errors, the stakes are much greater and the public's
      health must be protected through implementation of the peer-review system.

PMID- 9758977
TI  - Sibutramine (Meridia)--dental considerations for a new weight control drug.

PMID- 9758979
TI  - Porcelain laminate veneers: Part III.
AB  - Porcelain veneers have been an excellent esthetic alternative since introduced to
      dentistry. This column and those in the two previous issues have attempted to
      outline the important factors for the longest-term result. Following the
      guidelines, careful clinical judgment, and a high degree of mechanical skill can
      lead to unparalleled esthetic results.

PMID- 9758980
TI  - Chest pain as result of temporomandibular disorder (TMD).
AB  - Pain referred to the chest, with implications of cardiac distress, is described
      in a patient with a history of temporomandibular disorder (TMD). An anatomically
      based hypothesis is included to explain the reported chest symptoms. The basis
      for nociceptive neuronal interactions between the muscles of the head and neck
      has been reported previously. The patient described here suffered from myofascial
      pain of the muscles of mastication and the postural muscles of the head and neck.

PMID- 9758981
TI  - Stress in elective dental treatment: epinephrine, norepinephrine, the VAS, and
      CDAS in four different procedures.
AB  - This study focuses on progressive stress during defined, elective dental
      treatments, expressed in VAS, CDAS, and catecholamine excretion in urine.
      Fourteen male patients had avoided dental treatment for years; all were
      classified as ASA risk score I. The different dental sessions were: first visit
      after many years; check-up (nonpainful and nontraumatic); drilling and restoring
      under local anesthetics; drilling and restoring without local anesthesia; and
      extractions. Urine collection was performed directly before and after the
      sessions to measure epinephrine and norepinephrine concentrations. Anticipation
      stress was registered in the VAS, CDAS, and epinephrine excretion. Progressive
      stress was reflected in epinephrine increase, which discriminated between the
      different elective dental treatments.

PMID- 9758982
TI  - Wound healing and repair: a review of the art and science.
AB  - This chronological review of the major biological events that occur secondary to
      injury of mucoperiosteal tissue from either simple surgical wounding or trauma
      discusses the materials used to repair the compromised tissue surgically.
      Suturing techniques and post-surgical wound maintenance also are reviewed. The
      physiological stages of wound healing, factors affecting wound healing, and wound
      repair techniques are discussed.

PMID- 9758983
TI  - Hemangioma-like lesions: diagnosis and management.
AB  - The distinctive color that serves as the basis for the appearance of blue lesions
      arises from the accumulation of pigmented material, blood, or clear fluid in
      abnormal amounts within the oral tissues. Clinical appearance of these lesions
      varies and, despite their morphological similarity, their pathogenesis, etiology,
      and clinical behavior is different, as are their treatment and prognosis. Because
      of the clinical similarity between benign and malignant blue lesions (as
      illustrated by the patients described in this report), the need for precise
      histologic diagnosis prior to definitive treatment is emphasized.

PMID- 9758984
TI  - In vitro evaluation of the Thermafil technique with and without gutta percha
      coating.
AB  - To determine the sealing ability of the Thermafil technique with and without
      gutta percha on the plastic carrier, 40 maxillary incisors were divided into four
      treatment groups: (A) Thermafil with gutta percha on the carrier; (B) Thermafil
      without gutta percha on the carrier; (C) lateral condensation with standardize
      gutta percha; and (D) a single standardized gutta percha cone. Average leakage in
      groups A-D were 0.64 mm, 1.32 mm, 0.53 mm, and 0.72 mm, respectively. The only
      significant difference was between the Thermafil without gutta percha and the
      other three groups (p < 0.05).

PMID- 9758985
TI  - The clinical context and utility of tongue biopsies.
AB  - Lesions of patients' tongue biopsies are described to determine whether certain
      patients had predilections to develop various lesions based on gender or age, and
      to determine whether there were significant correlations between the diagnoses,
      which could be clinically useful, and the various patients. Surgical pathology
      specimens of the tongue were reviewed. Patients' gender, age and diagnoses were
      recorded. Most of the 399 patients surveyed were elderly. Patients with epidermal
      inclusion cysts or granular cell tumors were significantly younger than others.
      Men were younger than women with squamous cell dysplasia and carcinoma. Benign
      diagnoses were nearly equally distributed between men and women. Premalignant and
      malignant conditions were significantly more common among men than women. Follow
      up revealed a moderate degree of risk that a premalignant lesion may later
      develop frank malignancy.

PMID- 9758986
TI  - Concrescence: a case report.
AB  - A rare incident is described involving the extraction of a concrescence at the
      point of fusion of two maxillary posterior teeth and its management.

PMID- 9758987
TI  - Inflammatory papillary hyperplasia: supraperiosteal excision by the blade-loop
      technique.
AB  - Inflammatory papillary hyperplasia (IPH) is a benign, irreversible, persistent,
      and usually painless lesion of the oral mucosa that is the result of epithelial
      proliferation. Many surgical methods of treatment have proven to be not totally
      satisfactory in case of surgery, completeness of tissue removal, healing time, or
      patient comfort in the postoperative period. A relatively simple and effective
      procedure is proposed for the supraperiosteal excision of this lesion from the
      palate, using a razor blade cutting element and handle, called the blade-loop
      knife, or the Paquette knife handle. The blade-loop technique minimizes trauma
      and results in a short and comfortable postoperative period.

PMID- 9758988
TI  - A stress-releasing intracoronal attachment for extension base removable partial
      dentures.
AB  - Intracoronal retainer systems incorporated into splinted abutment restorations
      help force distribution. The additional torque introduced by the extension-based
      removable partial denture is applied over multiple abutments rather than to
      single abutment teeth. A fixed-removable prosthesis is proposed as a solution to
      this situation. The Thompson dowel nonlocking semiprecision attachment system is
      the intracoronal retainer of choice for distal extension denture bases. It allows
      controlled rotation or stress relief of the removable component by minimizing
      detrimental transfer of traumatic forces to the abutment teeth. The design and
      fabrication of the manufactured version of this retainer system is described.

PMID- 9758989
TI  - Removal of surface stains from enamel surfaces with at-home vital bleaching: a
      case report.
AB  - Stone model casts of a patient's maxillary and mandibular arches were used to
      fabricate a clear, soft, vacuum-formed custom mouth guard that was scalloped to
      end 1.0 mm supragingivally. The patient was given prophylaxis and oral hygiene
      home care instruction, and instructions regarding the placement of an at-home
      bleaching gel into the mouth guard and the mouth guard into the mouth. The
      patient was asked to wear the mouth guard for two hours daily before bedtime for
      one week and to return to the clinic for evaluation. This protocol was followed
      for three weeks for each arch. At the end of the three weeks, the stains on the
      most affected teeth were reduced dramatically.

PMID- 9758990
TI  - Defining prosthodontics.

PMID- 9758991
TI  - A definition of prosthetic dentistry.
AB  - PURPOSE: A more precise and up-to-date definition of prosthetic dentistry is
      warranted. The aim of the present review is to present a new core definition of
      the discipline on the basis of a discussion of existing definitions. MATERIALS
      AND METHODS: Clinical textbooks in prosthetic dentistry and dental implantology,
      as well as medical and dental glossaries were reviewed. RESULTS: Two main
      categories of definitions of prosthetic dentistry were identified: first,
      definitions that emphasized the technologic aspects of the discipline, i.e., the
      fabrication of prostheses; and second, definitions that incorporated some
      reference to the objectives or aims of prosthetic treatment, i.e., the
      restoration of one or more aspects of oral function. Slightly more than half of
      the citations contained such aim-related references, and this aspect tended to be
      most pronounced in recent publications. CONCLUSION: The following definition is
      ventured: prosthodontics is the discipline of dentistry concerned with the
      consequences of congenital absence or acquired loss of oral tissues and with the
      methods for and assessment whether more good than harm is done by inserting
      artificial devices made from alloplastic materials.

PMID- 9758992
TI  - Shade selection for single-unit anterior metal ceramic crowns: a 5-year
      retrospective study of 2,500 cases.
AB  - PURPOSE: The purpose of this study was to investigate the distribution of shades
      selected for metal ceramic crowns provided at a dental teaching hospital.
      MATERIALS AND METHODS: Data on the selection of shade for 2,500 metal ceramic
      crown units, placed over a 5-year period at the University Dental Hospital of
      Manchester, were collected and analyzed. Only those crowns placed adjacent to
      minimally restored vital teeth were included in the study. RESULTS: The results
      indicate that the most frequently chosen shades were in the mid-range of reddish
      brown hue. Furthermore, shades in the reddish-grey range of hue were rarely
      chosen. The selection of more than one shade for a crown ("mixed shades") was
      generally restricted to the maxillary anterior teeth. CONCLUSION: Knowledge of
      the distribution of shades selected for permanently luted metal ceramic crowns
      may be a useful adjunct in shade selection, particularly for the inexperienced
      operator.

PMID- 9758993
TI  - Adjustments and complications of mandibular overdentures retained by four
      implants. A comparison between superstructures with and without cantilever
      extensions.
AB  - PURPOSE: The aims of the study were to evaluate the postinsertion care needed by
      patients treated with four implants to retain mandibular overdentures and to
      compare two types of superstructures. MATERIALS AND METHODS: The study consisted
      of 54 patients who had been treated with conventional maxillary dentures and
      mandibular overdentures retained by four implants and a triple-bar superstructure
      with cantilever extensions (28 patients) or without cantilever extensions (26
      patients). Differences between both groups with regard to age, gender, length,
      and diameter of the implants and preoperative mandibular bone height were tested
      by means of Student's t and chi-square tests with a probability level of 0.05. No
      significant differences were found. Both groups were retrospectively compared on
      adjustments and complications. The follow-up period after insertion of the
      dentures was 2 years. RESULTS: During the 2-year follow-up, 17 patients of the
      cantilever-extension group and 20 patients of the group without cantilever
      extensions needed adjustments, and 17 patients of the cantilever group and 12
      patients of the group without cantilever extensions had to be treated because of
      complications. Significantly more (P < 0.05, chi-square test) superstructure
      fractures were present in the cantilever group (14 occasions in 7 patients) than
      in the group without cantilever extensions (1 occasion). All superstructure
      fractures in the cantilever group involved the cantilever extensions. CONCLUSION:
      This study demonstrated a considerable need for postinsertion care, confirming
      the necessity of routine follow-up services for patients restored with implant
      retained overdentures. Furthermore, the results of this study suggest restriction
      of the use of cantilever extensions.

PMID- 9758994
TI  - Customized titanium single-implant abutments: 2-year follow-up pilot study.
AB  - PURPOSE: The aim of this study was to describe an alternative technique to
      fabricate single-implant restorations by using adjustable titanium abutments with
      porcelain applied directly to the abutment, and to follow an early group of
      patients treated with these crowns. MATERIALS AND METHODS: Seventeen randomly
      selected single crowns were consecutively placed in 14 patients and then followed
      for 2 years. A protocol of using healing abutments, implant impressions, and
      adjustment of the final abutment in the laboratory was used to fabricate the
      crowns. RESULTS: The clinical result revealed few clinical problems, and the mean
      marginal bone loss was 0.4 mm (standard deviation +/- 0.57 mm) after 1 year in
      function. CONCLUSION: The conclusion drawn, based in part on published
      literature, was that occurrence of mucosal inflammation and marginal bone loss
      was not related to the use of the present protocol.

PMID- 9758995
TI  - Differences between traces of adjacent condylar points and their impact on
      clinical evaluation of condyle motion.
AB  - PURPOSE: Recent research revealed that traces of single posterior reference
      points can depend on the location of the monitored point. The aim of this study
      was to quantify this dependence and to point out its consequences for clinical
      application of condylar path registrations. MATERIALS AND METHODS: In 60
      asymptomatic volunteers, mandibular motion was recorded during protrusion,
      lateral excursion, and opening-closing of the jaw. Simultaneous trace-patterns of
      10 condylar points including the hinge-axis point and the kinematic-axis point
      were compared with respect to length, inclination angles, coordination, and
      shape. RESULTS: In protrusion, traces of the different condylar points were equal
      and independent of the location of the monitored point. Bennett angles depended
      on the sagittal position of the reference point and varied by 0.8 degree per 1 mm
      change of location. Opening-closing traces differed considerably. Their lengths
      varied by up to 9 mm and inclination angles varied by 40 degrees. Opening-closing
      patterns also showed irregularities like those observed in temporomandibular
      disorders. Irregularities were minor for the hinge-axis point and least for the
      kinematic-axis point. CONCLUSION: In tooth-guided movements "condyle motion" is
      represented by the traces of any point near the condyle. In opening-closing,
      however, the trajectory of a single condylar point will not reliably represent
      condylar motion. For articulator adjustment, condylar angles must not be taken
      from opening-closing, but only from protrusion. In diagnostic applications, one
      has to be aware that irregular traces may not only result from dysfunction, but
      may as well be a result of the choice of reference point.

PMID- 9758996
TI  - Marginal distortion of thermally incompatible metal ceramic crowns with
      overextended margins.
AB  - PURPOSE: The present study tested the hypothesis that metal ceramic crowns with a
      varying axial height are more susceptible to marginal distortion during
      mechanical and thermal processing treatments than crowns with a uniform axial
      height. MATERIALS AND METHODS: Copings of Pd-Cu-Ga alloy with buccal margin
      extensions of 0, 1.5, and 3.0 mm were prepared. Oxidized copings were veneered
      with experimental opaque porcelain with a mean thermal contraction coefficient
      (25 degrees C to 500 degrees C) that was either 2.1 ppm/degree C below (delta
      alpha = +2.1 ppm/degree C) or 0.1 ppm/degree C above (delta alpha = -0.1
      ppm/degree C) that of the alloy. Nine groups of six specimens each were prepared
      for analysis. Eighteen copings from these 54 specimens were used as porcelain
      free controls. All specimens were subjected to a 10-step procedure including
      grinding, oxidation, firing of four opaque porcelain layers (O1: 0.15 mm; O2:
      0.15 mm; O3: 0.5 mm; O4: 0.5 mm), glazing, abrasive blasting for 15 seconds,
      removal of ceramic by dissolution in hydrogen fluoride, and a postannealing
      treatment. The control specimens were also subjected to this procedure with the
      exception of the firing of four layers of porcelain, which were not applied.
      Marginal gap width was determined using a measuring microscope at a magnification
      of 30x. RESULTS: Analysis of variance revealed a significant difference in mean
      gap width as a function of axial length. The largest gap change was associated
      with a 3.0-mm buccal extension and the negative mismatch condition (delta alpha <
      0). CONCLUSION: Marginal distortion of crowns decreases as the axial length
      becomes more uniform. Analysis of crown distortion based on differences in the
      mean contraction coefficients of metal and porcelain alone is not recommended
      because it ignores the effects of metal grinding, metal sandblasting, and
      transient stress.

PMID- 9758997
TI  - Effects of preparation and luting system on all-ceramic computer-generated
      crowns.
AB  - PURPOSE: Computer-aided design/computer-integrated machining (CAD/CIM) allows
      defect-oriented custom-shaping of the inside surfaces of all-ceramic crowns. The
      purpose of this study was to examine the effect of inside crown form on fracture
      strength of cemented and bonded crowns. MATERIALS AND METHODS: Four preparation
      types were used: (1) "classic" with a butt shoulder of 1.2 mm, abutment height of
      4 mm, and 6-degree convergence, (2) like type 1 with mesio-occlusodistal cavity,
      (3) like type 1 with height reduced by 50%, and (4) like type 1 with abutment
      reduced by 100% plus a pulp chamber cavity. Crowns were CAD designed on
      preparations 1 to 4 using identical outside morphology. Machined crowns were
      placed on abutments (a) without any media as controls (n = 15), (b) cemented (n =
      15), and (c) bonded (n = 15), and were loaded until fracture. RESULTS: Zinc
      phosphate-cemented crowns (1b, 2b, 3b, and 4b) showed significant (P < 0.001)
      increase of fracture load values compared to uncemented control crowns (1a, 2a,
      3a, 4a). Fracture load values of bonded crowns (1c, 2c, 3c) were significantly (P
      < 0.001) higher than those for cemented crowns. Bonded crowns with thick occlusal
      dimensions (3c and 4c) showed the highest fracture load values. CONCLUSION:
      Bonded all-ceramic CAD/CIM crowns with defect-oriented inside morphology and
      increased occlusal dimensions showed high fracture load values.

PMID- 9758998
TI  - Effect of water storage on the flexural properties of E-glass and silica fiber
      acrylic resin composite.
AB  - PURPOSE: The aim of this study was to determine the effect of water on the
      flexural properties of fiber-reinforced denture base polymers. MATERIALS AND
      METHODS: Continuous woven silanized electrical glass, or E-glass, fibers and
      woven silica fibers were used to reinforce heat-cured and autopolymerized denture
      base polymers. Fibers were oriented at a 45-degree angle to the long axis of the
      test specimens. Control specimens were unreinforced. Dry test specimens and those
      stored in water for up to 48 weeks were tested with a three-point loading
      apparatus. The surfaces of the fibers of the test specimens stored dry or 48
      weeks in water were analyzed with a scanning electron microscope to evaluate the
      degree of adhesion between fibers and polymer matrix. RESULTS: The ultimate
      transverse strength of unreinforced and reinforced denture base polymers
      decreased during 48 weeks' storage in water (P < 0.05, one-way analysis of
      variance, n = 5), and most of this reduction occurred during the first 4 weeks of
      storage in water. The flexural modulus of the unreinforced test specimens
      decreased significantly (P < 0.001), whereas there was less, if any, change in
      the flexural modulus of the fiber-reinforced test specimens. Scanning electron
      microscopic examination revealed no differences in adhesion of E-glass fibers to
      the polymer matrix when the specimens stored in water were compared with those
      stored by. Reduced adhesion between the silica fibers and matrix was observed
      after 48 weeks' storage in water. CONCLUSION: The results of this study suggest
      that the ultimate transverse strength of the E-glass fiber-reinforced test
      specimens decreased 14% and that of the silica fiber-reinforced test specimens
      decreased 36% after 48 weeks of storage in water.

PMID- 9758999
TI  - Five-year prospective study of prosthodontic and surgical single-tooth implant
      treatment in general practices and at a specialist clinic.
AB  - PURPOSE: The aim of this 5-year prospective study was to compare the results of
      single-tooth implant treatments planned and performed at four general
      practitioners' offices with the results from a specialist clinic. MATERIALS AND
      METHODS: The group comprised 38 patients. Nineteen patients, with 19
      implants/crowns, were planned and treated by four general practitioners, and the
      outcome was compared to a matched group of patients from a specialist clinic.
      RESULTS: Three patients did not complete the study. None of the implants failed;
      one crown failed. This was a very positive result, as the single failure, a crown
      at the specialist clinic, was caused by an extraordinary trauma and was not
      related to a common cause such as bite forces or fatigue. No significant
      differences were observed between the groups when the radiographic findings were
      compared. Some minor differences, for bleeding and the position of the mucosal
      level around implants and adjacent teeth, were observed between the two groups.
      CONCLUSION: The small discrepancies that were observed between treatment
      performed by the four general practitioners at their own offices and treatment
      performed at the specialist clinic were not regarded to be of any clinical
      importance. This indicates that complete single-tooth implant treatment may be
      performed for many patients by general practitioners who have received adequate
      training, allowing the possibility of referring complicated treatments to
      specialists and other treatments to general practitioners.

PMID- 9759001
TI  - Make teeth--and money!

PMID- 9759000
TI  - Use of wide-diameter and standard-diameter implants to replace single molars: two
      case presentations.
AB  - PURPOSE: The ultimate goal in modern esthetic dentistry is the restoration of
      lost hard and soft tissues by imitating nature as closely as possible. With the
      increasing esthetic awareness of patients, surgical and technical developments,
      and dentists' enhanced skills and knowledge, optimal function and esthetics are
      achievable even with implant-supported restorations in molar regions. Anatomic
      and morphologic factors and poor bone quantity and quality might reduce success
      rates of dental implants in the posterior jaw. Today, there are two options to
      replace a single missing molar by an implant-supported crown: the single wide
      diameter implant or two standard-diameter implants. These two approaches are
      described and their advantages and disadvantages discussed in two exemplary
      clinical cases. MATERIALS AND METHODS: In one case, the edentulous ridge in the
      area of the mandibular right first molar (FDI tooth 46) provided sufficient
      mesiodistal space to restore tooth 46 with a porcelain-fused-to-metal crown on
      two standard-diameter implants, placed in a root-analog manner. In the other
      case, the manibular first molars (FDI teeth 36 and 46) were replaced by porcelain
      fused-to-metal crowns on wide-diameter implants. RESULTS: It can be concluded
      that both options to replace a single molar provide more surface area and better
      biomechanical properties than one standard implant. CONCLUSION: Long-term data
      are needed before these treatment modalities can be recommended for the private
      practitioner.

PMID- 9759002
TI  - A new twist on single screw-retained implant restorations.
AB  - Several laboratories have stopped accepting implant cases because of the
      technical demands and the additional labor time required to process them. This
      article will discuss the IMPAC PDQ abutment (Vident, Brea CA). This abutment
      offers technicians a simple, reliable method for producing a strong, high quality
      implant substructure ready for porcelain application in a matter of minutes.

PMID- 9759003
TI  - Putting their artistic skills to use: Georgia high school students learn a craft-
      and make money at the same time.

PMID- 9759005
TI  - Why aren't dental technicians paid more?

PMID- 9759004
TI  - Training our trainers: dental laboratory management's challenge for the next
      decade.
AB  - Training has been shown to be an important factor in the growth of successful
      dental laboratories. Many technicians have received extensive laboratory and
      managerial training in the midst of technician shortages, more sophisticated
      techniques and products. What can we do to insure the manpower needs of the
      dental laboratory industry will be met in the future? A potential answer is
      learning and developing the skills to train our supervisors who train our
      trainees. We must remember, however, the focus of effective training is not the
      product (books, tapes, slides, etc), but the processes we bring to the training
      arena. Understanding and implementing the S.M.A.R.T. system for training goals,
      having a thorough and workable knowledge of adult learning theory, spaced
      repetition, and the seven W's will assure the laboratory owner that he will be
      able to effectively address the manpower and training needs of a profession
      moving quickly in the new millennium.

PMID- 9759006
TI  - To be, or not to be, a technician.

PMID- 9759007
TI  - Self respect.

PMID- 9759008
TI  - Direct/indirect band placement.
AB  - This article describes orthodontic band placement in alginate impressions. The
      fitting of orthodontic bands at the chair and the indirect transfer of the bands
      to the impression influences the fit and function of the preventive or
      interceptive orthodontic appliance being fabricated. Some of the problems
      associated with the transfer of bands to impressions will be presented. In
      addition, a discussion of methods to eliminate these problems is included.

PMID- 9759009
TI  - A method of making decalcifications in the porcelain build up.
AB  - This article describes a method for making white decalcifications or modeling
      characterizations that attempt to duplicate natural teeth. Common techniques
      often use white stain applied to the wet porcelain or painted on as surface
      stain. A simplified and reproducible technique is provided that allows this
      characterization to be completed as part of the porcelain build up. A mixture of
      three powders causes an improved appearance that can lighten the incisal and
      occlusal surfaces to help create greater contrast with the body porcelain for a
      more natural result.

PMID- 9759010
TI  - Discipline: the most misunderstood word for laboratory management and its
      employees.

PMID- 9759011
TI  - 'Spiders' offer easy access to index-liked performance.

PMID- 9759012
TI  - A conversation with the NBC chairman: a way I thought I could contribute.

PMID- 9759013
TI  - Case 3: Replantation of vertically fractured tooth.

PMID- 9759014
TI  - Effects of dentin bonding agents on macrophage mitochondrial activity.
AB  - Dentin bonding agents (DBA) have been considered for use as root-end fillings.
      Previous studies have documented the release of DBA components in vivo and in
      vitro, but the biological implications are not clear. The macrophage is important
      in wound healing, and likely to be important in any inflammatory response.
      Therefore, this study determined the concentrations of the components of DBAs
      that suppress the mitochondrial activity of human macrophages in vitro. THP-1
      macrophages were cultured in the presence of four DBA components (2-hydroxyethyl
      methacrylate (HEMA), 4-methacryloxyethyl trimellitate anhydride (4-META),
      bisphenol-glycidylmethacrylate (Bis-GMA), and urethane dimethacrylate (UDMA)) at
      various concentrations and for varying durations. Residual effects were also
      measured after the resins were removed. Controls received only the vehicle
      solution, ethanol or water. THP-1 mitochondrial activity was estimated using the
      MTT assay, and the 50% toxicity concentrations (TC50) were determined
      graphically. Resin components suppressed the mitochondrial activity of
      macrophages at different concentrations (TC50 values for HEMA (10,000 mumol/L), 4
      META (3,800 mumol/L), Bis-GMA (130 mumol/L), and UDMA (110 mumol/L) at 24 h, and
      the effect was time-dependent. Residual effects were observed for all resins.

PMID- 9759015
TI  - Cytotoxic effect of endodontic bacteria on periapical fibroblasts.
AB  - This study was conducted to investigate the effects of sonicated bacterial
      extracts (SBEs) from anaerobic Gram-negative bacteria on periapical fibroblast
      obtained from the apical portion of human periodontal ligaments. Porphyromonas
      endodontalis, Porphyromonas gingivalis, Prevotella intermedia, and Fusobacterium
      nucleatum were chosen from among the endodontic bacteria isolated from root
      canals having a periapical lesion and compared in terms of their cytotoxicity.
      The purpose of this study was to examine which bacteria are involved in the
      development of periapical inflammation. The anaerobes were cultured under strict
      anaerobic conditions, and the bacterial cells were then harvested by
      centrifugation after incubation. The concentrated cell suspensions were sonicated
      and subsequently centrifuged. An SBE was made of each of the filtered
      supernatants. Each SBE was added to cultures of periapical fibroblasts. The cell
      growth and proliferation were measured by the MTT method after 3, 5, and 7 days.
      The SBEs from P. endodontalis, P. gingivalis, and F. nucleatum inhibited the
      growth of the fibroblasts, whereas the SBE from P. intermedia did not inhibit it.
      The SBEs from P. gingivalis and F. nucleatum inhibited the fibroblast growth more
      strongly than did the P. endodontalis, P. gingivalis, and F. nucleatum may
      participate in the development of periapical lesions.

PMID- 9759016
TI  - A new muffle model system to study root canal morphology and instrumentation
      techniques.
AB  - A new muffle model system is presented using the principle of internal indexing.
      The system is composed of a metal stand, four pins, and a single Teflon mold that
      is used for the investment of all teeth. This system is very precise,
      reproducible, and versatile. The sectioned specimens can easily be stored
      assembled, as opposed to previous systems that rely on external indexing.

PMID- 9759018
TI  - Efficacy of Er:YAG laser irradiation in removing debris and smear layer on root
      canal walls.
AB  - The purpose of this study was to evaluate the efficacy of Er:YAG laser
      irradiation in removing debris and smear layer from prepared root canal walls.
      Thirty-six human extracted mandibular incisors teeth were divided into three
      groups. Group 1 (G1) was control specimens that were not lased. The teeth of
      group 2 (G2) and group 3 (G3) were irradiated by Er:YAG laser at different watt
      powers of 1 W and 2 W. The teeth were bisected and prepared for study in
      stereoscopic light microscope and SEM. Control specimens showed an amount of
      debris and heavy smear layer obscuring the dentinal tubules at all levels in the
      canals. The root canal walls irradiated by Er:YAG laser were free of debris, with
      an evaporated smear layer and open dentinal tubules. Statistical analyses showed
      significant differences (p < 0.01) in cleanliness smear layer between G1 and G2,
      and G1 and G3. However, there was no statistically significant difference between
      G2 and G3 in the cleanliness of the middle and apical one-third of the root
      canals. These results show Er:YAG laser is effective in removing debris and smear
      layer from root canal walls.

PMID- 9759017
TI  - Cellular response to Mineral Trioxide Aggregate.
AB  - This investigation studied the cytomorphology of osteoblasts in the presence of
      Mineral Trioxide Aggregate (MTA) and examined cytokine production. MTA and
      Intermediate Restorative Material (IRM) were prepared and placed in separate
      Petri dishes. Osteoblasts (cell-line MG-63), grown to confluence in Hams
      F12/Dulbecco's modified Eagle's medium, were seeded into the dishes, which were
      incubated for 1 to 7 days. The specimens were viewed by scanning electron
      microscopy. For cytokine evaluation, cells were grown either alone or in other
      dishes containing the test materials for 1 to 144 h. Media were removed for ELISA
      analysis of interleukin (IL)-1 alpha, IL-1 beta, IL-6, and macrophage colony
      stimulating factor. Scanning electron microscopy revealed healthy cells in
      contact with MTA at 1 and 3 days; in contrast, cells in the presence of IRM
      appeared rounded. The ELISA assays revealed raised levels of all ILs at all
      periods when cells were grown in the presence of MTA; in contrast, cells grown
      alone or with IRM produced undetectable amounts. The macrophage colony
      stimulating factor was produced by cells irrespective of the group. It seems that
      MTA offers a biologically active substrate for bone cells and stimulates IL
      production.

PMID- 9759020
TI  - Long-term seal provided by some root-end filling materials.
AB  - A tight and long-lasting seal of root-end fillings is of prime clinical
      importance. A hundred standard bovine root sections, each 3 mm high and with a
      central pulp lumen of 2.6 mm in diameter, were filled with five commonly used or
      potential root-end filling materials. At 24 h, or at 3, 6, or 12 months after
      filling, leakage along these filling materials was determined under a low
      headspace pressure of 10 kPa (0.1 atm) using a fluid transport model. During the
      first 3 months, the percentage of gross leakage (> 20 microliters day-1)
      increased noticeably for Tytin amalgam (from 20 to 100%) and Super-EBA (from 0 to
      55%), whereas it decreased noticeably for mineral trioxide aggregate (MTA; from
      55% to 0%). Thereafter, the increased leakage of amalgam and Super-EBA decreased
      with time, whereas the improved seal of MTA was maintained until the end of the
      experiment. At 3-, 6-, and 12-month time intervals, both glass ionomer cements
      (Fuji II and Hi Dense) and MTA showed less leakage than the conventional amalgam
      and Super-Eba, of which amalgam leaked more.

PMID- 9759021
TI  - Rapid sterilization of gutta-percha cones with glutaraldehyde.
AB  - Five commercially available liquid glutaraldehyde preparations (Glutaron II,
      Cidex 28, Glutalabor, Banicide, and Anti-G-Plus) were compared for effectiveness
      in sterilizing gutta-percha cones artificially contaminated with Bacillus
      subtilis ATCC 6633 spores. Sporicidal activity differed for the various brands of
      cones, but after 15 min all glutaraldehyde solutions were effective in
      eliminating the spores. However, three solutions (Cidex 28, Banicide, and Anti-G
      Plus) showed sporicidal activity within a shorter time (10 min). All
      glutaraldehyde solutions tested may be used in endodontic practice for rapid
      decontamination of gutta-percha cones, thus contributing to the maintenance of
      the aseptic chain, an essential factor for successful root canal treatment.

PMID- 9759019
TI  - Subjective sensation and objective neural discharges recorded from clinically
      nonvital and intact teeth.
AB  - The aim of this study was to compare subjective sensation with objective neural
      discharges recorded by microneurography. We examined human teeth that did not
      respond to pulp vitality testing, but that responded to cavity preparation for
      endodontic treatment (pathophysiological). Intact teeth and endodontically
      obturated teeth were used as controls. Pulpal blood flow in the clinical crown
      and histological examination were also used. Most teeth, both in normal and
      pathophysiological conditions, did not respond to all pulp vitality tests. Even
      when teeth in the pathophysiological group showed spike discharges evoked by pulp
      vitality tests or from spontaneous activity no sensation was elicited. These
      results confirmed the usefulness of microneurography for research on pulpal
      sensation and the significance of summation in the perception of sensation in
      chronically inflamed tooth pulp.

PMID- 9759022
TI  - Effects of eugenol and noneugenol endodontic sealer cements on post retention.
AB  - Resin cements are sometimes recommended to enhance the retention of posts in
      endodontically treated teeth. Many sealer cements used in endodontics contain
      eugenol, however, which has been shown to inhibit the polymerization of resins.
      The purpose of this study was to evaluate the effects of a eugenol and a
      noneugenol sealer cement on the retention of posts. Sixty extracted canines were
      divided equally into four groups. Each tooth received conventional endodontic
      therapy and was prepared to receive a post. Two sealer cements were used in
      obturation: one contained eugenol and one was eugenol-free. The posts were
      cemented with either zinc phosphate cement or resin cement. Each combination of
      sealer and post cement was tested for retention on an Instron testing machine.
      The type of sealer used had no effect on post retention with either cement. Post
      retention was significantly greater with the zinc phosphate cement than the resin
      cement.

PMID- 9759024
TI  - Resistance to fracture of three all-ceramic systems.
AB  - All-ceramic restorations have become an attractive alternative to porcelain-fused
      to-metal crowns, but their strength is still an important issue. The purpose of
      this study was to compare the in vitro fracture resistance of three all-ceramic
      systems: IPS Empress, In-Ceram, and Procera AllCeram. Thirty dies were replicated
      from a master die using high filler resin with a modulus of elasticity similar to
      dentin. Ten cores each of In-Ceram and Procera were fabricated to a thickness of
      0.5 mm. The remaining porcelain was applied using a sculpting device to produce a
      crown with a final thickness of 1.0 mm axially and 2.5 mm occlusally. Ten IPS
      Empress crowns were mixed to the same dimensions and were pressed by the
      manufacturer. The internal surfaces of all the crowns were etched and silanated
      prior to cementation with a resin cement (Panavia 21). The cemented samples were
      loaded in an Instron machine until fracture. The mean fracture loads were: IPS
      Empress, 222.45 (+/- 49) kg; In-Ceram, 218.8 (+/- 36) kg; Procera AllCeram,
      194.20 (+/- 37) kg. Tukey's test showed no statistically significant differences
      among the three all-ceramic systems at p < .05.

PMID- 9759023
TI  - Polyethylene ribbon and fixed orthodontic retention and porcelain veneers:
      solving an esthetic dilemma.
AB  - The patient, a 58-year-old woman, had started orthodontic treatment to correct
      spacing between the maxillary anterior teeth 6 year prior to presentation with a
      chief complaint of tooth discoloration and spacing. The treatment had consisted
      of the use of a removable appliance to retract the maxillary anterior teeth. The
      patient continued to wear the appliance sporadically. When she presented, the
      maxillary incisors were in primary occlusal trauma with Grade 2 mobility. The
      patient discontinued wearing the appliance. The periodontal condition was
      addressed with initial therapy. As part of the treatment plan to stabilize the
      maxillary anterior teeth and provide the patient with an esthetic result, it was
      decided to do a limited occlusal adjustment of the maxillary anterior teeth to
      control fremitus, and to place a fixed, composite resin, polyethylene ribbon
      reinforced splint, using a facial approach. The esthetic restoration of these
      teeth was accomplished with bonded porcelain veneers.

PMID- 9759025
TI  - Porcelain veneers: adjunct or alternative to orthodontic therapy.
AB  - Elective esthetic dentistry defines "art form" within the field of dentistry.
      Most frequently, a clinical team of skilled professionals is required to satisfy
      the discriminating patient who presents with an esthetic-driven agenda. This
      article describes a patient who has rejected orthodontic therapy but continues to
      seek esthetic alternatives. Porcelain laminate veneers were an appropriate
      alternative in this case. The second case demonstrates the synergy of combined
      therapies that were explained to the patient and strategized from the onset to
      facilitate a result not obtainable by a singular approach. One should not infer
      that porcelain laminate veneers are an automatic substitute for orthodontic
      therapy. There may be instances when this is required; however, in most
      instances, conservative esthetic therapies, such as porcelain laminate veneers,
      supplement orthodontic therapy to create a final result not possible with either
      singular approach.

PMID- 9759026
TI  - Esthetic restoration of endodontically treated teeth: factors that affect
      prognosis.
AB  - Restoration of endodontically treated teeth involves a complex system of
      components and component interfaces designed to resist force. Dental materials,
      forces on teeth, clinical circumstances, and restorative design determine
      restoration success. A new classification evaluates number of canals, amount of
      remaining tooth surface, chamber space, canal quality, and canal orientation.

PMID- 9759027
TI  - Procedures for enamel and dentin conditioning: a comparison of conventional and
      innovative methods.
AB  - Composite materials have become an integral part of the wide range of filling
      materials currently available. Conditioning is necessary to achieve adequate
      bonding of the composite material to enamel and dentin. Normally, this is done by
      applying acid preparations to the dental surfaces. These acids have an etching
      effect that causes surface roughening. The increasing application of lasers in
      dentistry has introduced another possibility. Laser irradiation can cause
      roughening of enamel and dentin surfaces. Another interesting alternative is the
      so-called kinetic cavity preparation technique. This method also results in
      distinct surface roughening. The purpose of the present study, was to compare the
      described methods. Tensile bond strength tests and shear bond tests were carried
      out to examine the adhesion of a composite material to surfaces treated with
      these methods. Laser irradiation with certain devices and the air-abrasive
      technique yielded results similar to those with acid etching.

PMID- 9759028
TI  - "The view" and the canine connection: an atlas of mandibular anterior tooth
      esthetics.
AB  - Restoring splinted mandibular incisors and canines with full crown restorations
      has always presented a challenge in creating an esthetic illusion of reality of
      normal individual teeth. This treatise is designed to present the rules for
      mandibular anterior esthetics that have been distilled from almost 4 decades of
      clinical practice of restoring dentitions that have been severely compromised by
      the deformities of disease or accident. The resultant formula systematically
      creates the desired results with a high degree of predictability.

PMID- 9759029
TI  - Soft tissue modeling for the esthetic single-tooth implant restoration.
AB  - The ability of the restorative dentist to understand and control the relation of
      the implant to its associated gingival tissues is extremely important in
      achieving the maximum esthetic result in the final restoration. The position of
      the gingival margin following stage-two surgery represents collapse of the
      gingival tissues until it finds support by the component against which it comes
      to rest. This component may be a healing abutment, final abutment, or provisional
      restoration, if placed at the same time of implant exposure. Generally, it will
      be a healing abutment. There is complex relation between implant position,
      gingival management at stage-one and stage-two surgery, the position of the
      gingival margin over the buccal surface of the implant compared to the adjacent
      natural teeth, component selection, and lip line esthetics. The therapist who
      understands these relations will know how to mold the gingival tissue around
      implants to maximize the esthetic result. This article focuses on these relations
      and the technique of tissue modeling with subgingival contours to create a
      restoration with the illusion of reality.

PMID- 9759030
TI  - Use of prosthesis-generated computed tomographic information for diagnostic and
      surgical treatment planning.
AB  - Diagnosis, treatment planning, and prediction of a final implant-supported
      prosthetic outcome require precise noninvasive presurgical information. By
      combining the use of a clinically verified barium-coated template and interactive
      computed tomography (SIM/Plant, Columbia Scientific, Inc., Columbia, Maryland),
      the implant team can determine and address the relevant issues affecting
      treatment outcomes. Those issues include: implant-prosthesis incompatibility,
      recognition of anatomic limitations and anomalies, the need for presurgical bone
      augmentation, implant diameter and distribution, abutment type and angle, bone
      density, soft tissue augmentation requirements, accurate fee determination, and
      medicolegal protection. The data collection methodology and format for the Mecall
      and Rosenfeld prosthesis prediction analysis are discussed as part of case
      presentation.

PMID- 9759031
TI  - Fifty years of interdisciplinary site development: lessons and guidelines from
      periodontal prosthesis.
AB  - Just as "osseointegration" became synonymous with successful restoration of
      function in the fully edentulous patient during the 1980s, the term "implant site
      development" has become intricately associated in the 1990s with the techniques
      used to achieve esthetic results with implants in the partially edentulous
      patient. This article explores the roots of the concept of site development
      within the philosophy and principles of periodontal prosthesis. In addition, the
      myriad of techniques that are presently collectively referred to as site
      development are systematically classified into a sequential four-tiered approach
      that optimizes their efficient application as well as overall success.

PMID- 9759032
TI  - Biologic width and its relation to periodontal biotypes.
AB  - Although average measurements of the biologic zone do not necessarily reflect any
      one clinical situation, they do establish a basis upon which clinical decisions
      can be made. Clinical impressions, human autopsy material, and animal studies
      support the concept of a biologic width. Impingement on the attachment in a
      susceptible host has shown adverse reactions, including gingival inflammation and
      alveolar bone loss. The concept is clinically important in determining the extent
      of osseous surgery necessary in the exposure of sound tooth structure. If the
      implant-abutment interface is considered to be similar to a subgingival crown
      margin, its importance in relation to peri-implant inflammatory disease is
      readily apparent. In the presence of inflammation, it is likely that epithelial
      migration would occur to a level apical to that source. Clinical observations
      indicate that, once the biologic attachment is invaded around the implant, the
      gingival reactions are similar to those found around natural teeth, whether the
      tissue is of the thick flat or thin scalloped type.

PMID- 9759033
TI  - Sinus floor elevation with osteotomes.
AB  - This article describes a new methodology for augmentation of the bone at the
      sinus floor that is less invasive than previous techniques. This procedure is
      called the osteotome technique. Two different applications of the osteotome
      technique are described. First an implant site is created in a location that
      previously had inadequate bone for immediate fixation of an implant. In a second
      surgical step additional augmentation of the bone is carried out when the implant
      is inserted. This case report provides details, from the original ridge defect
      with 1 to 2mm of bone under the low sinus to the final esthetic crown restoration
      on a 5 x 13-mm external-hex screw implant that is supported by newly generated
      bone.

PMID- 9759034
TI  - Implants as anchorage in orthodontics: a clinical case report.
AB  - Often, in dental reconstruction, orthodontics is required for either functional
      or aesthetic reasons. Frequently, the critical anchorage necessary to move the
      teeth may be lacking. This article documents how critically located implants can
      be used as anchorage during orthodontic treatment and can become definitive
      support for the final reconstruction. Osseointegrated implants in this manner
      achieved a more ideal and acceptable result for this patient.

PMID- 9759036
TI  - The complete mandibular subperiosteal implant: an overview of its evolution.

PMID- 9759035
TI  - Effects of chemotherapy on osseointegration of implants: a case report.
AB  - A patient underwent mandibular resection for high-grade osteosarcoma with
      immediate reconstruction with a microvascular fibula free bone graft and
      simultaneous placement of osseointegrated implants. Following initial healing,
      she underwent six cycles of chemotherapy and had further revision surgery prior
      to implant exposure and construction of a prosthesis. The chemotherapy appears to
      have had no deleterious effects on implant osseointegration or survival.

PMID- 9759037
TI  - Tripodal mandibular subperiosteal implant: basic sciences, operational
      procedures, and clinical data.
AB  - A tripodal mandibular subperiosteal dental implant is a three piece cast metal
      framework that fits on the residual ridge beneath the periosteum and provides
      support for a dental prosthesis by means of posts or other mechanisms protruding
      through the oral mucosa. This implant is indicated in patients with advanced
      atrophy of the mandible where the unstable alveolar bone has completely
      disappeared, leaving in place the more stable basal bone with specific anatomical
      contours. The authors present their experience of 317 cases carried out in three
      different centers related to this implant modality and underline the importance
      of the basic anatomic, physiologic, and medical knowledge required to optimize
      the results.

PMID- 9759039
TI  - Implant dentistry today.

PMID- 9759038
TI  - Oral microbiota and implant type membranes.
AB  - Candida albicans (Ca), Staphylococcus aureus (Sa), Streptococcus sanguis (Ss),
      Actinomyces naeslundii (An), Actinomyces odontolyticus (Ao), Porphyromona spp (P
      spp), Candida glabrata (Cg), Candida krusei (Ck), and Rhodotorula spp (R spp)
      were tested with equal pieces of biodegradable membranes. Membranes pretreated
      with saliva or clorhexidine and nontreated control membranes were tested in three
      different culture media containing 0.1 mL homologous suspension for each strain
      under study. Incubation was performed at 37 degrees C for 48 hours for aerobiosis
      and for five days for anaerobiosis. Macroscopy and microscopy were carried out.
      Membranes were removed, washed, and resuspended. Samples were sonicated, and the
      supernatant was disseminated on brain heart infusion broth or blood agar.
      Incubation was repeated, colony-forming unit counts were performed, and
      statistical analysis was carried out using analysis of variance transforming
      results to Log10 (x + 1), the highest interaction level was used to calculate
      standard error. Orthogonal contrast was used to compare the different
      microorganisms under study. Highest adhesion was found with Ca, Cg, Ck, Sa, and
      Ss. A sufficient quantity of Actinomyces could not be recovered from the
      membranes. Results with P spp were poor, confirming lower gram-negative adhesion.
      Replicate flasks with Ss and Ca were cultivated. Membranes were removed after
      washing and subjected to scanning electron microscopy, as were untreated control
      pieces. A cavelike surface was observed. Streptococcus sanguis adhering to the
      membranes showed extracellular projections. Candida and gram-positive cocci
      showed great recovery capacity.

PMID- 9759040
TI  - Orofacial pain uptake. 1.

PMID- 9759041
TI  - Volunteerism that spans the globe.

PMID- 9759042
TI  - An evaluation of differences and similarities observed in fixture failure of five
      distinct implant systems.
AB  - While the long-term success of osseointegrated implants has been demonstrated in
      the dental literature, implant failure does occur as a result of various factors.
      The purpose of this investigation was to identify clinical and/or microbiological
      differences associated with failure in five implant systems. At the conclusion of
      this 7.5-year investigation, 67 of 958 implants were determined to have failed.
      An overall failure rate of 7.0% was evident in this study, which, depending on
      the particular system, ranged from 4.7% to 15.2%.

PMID- 9759043
TI  - The extracted tooth pontic--provisional replacement during bone graft and implant
      healing.
AB  - When tooth extraction is required, a provisional restoration may be utilized as
      an interim prosthesis during bone graft and implant healing. The selection of
      provisional replacement of the anterior teeth following extraction may have a
      direct influence on the success of the definitive tooth replacement. This article
      describes a technique for using the extracted tooth or a denture tooth as an
      interim prosthesis during bone graft and implant healing. This method of
      provisionalization offers several advantages, including no adjacent tooth
      preparation, natural appearance, and retention of the papillae.

PMID- 9759044
TI  - Controlled restorative treatment of compromised anterior dentition.

PMID- 9759045
TI  - Use of acellular dermal matrix for increasing keratinized tissue around teeth and
      implants.

PMID- 9759046
TI  - The use of transitional implants for immediate fixed temporary prostheses in
      cases of implant restorations.
AB  - While the original Branemark implant protocol has continued to evolve, the
      avoidance of implant loading during osseointegration remains a prerequisite with
      all implant systems. Immediately loaded transitional implants have recently been
      developed to support the fabrication of a fixed provisional prosthesis that
      provides implant patients with improved aesthetics and function during the
      osseointegration period. In this manner, osseointegration can occur free from
      prosthetic and transmucosal loads. This article describes the use of transitional
      implants and presents a classification of three different case types.

PMID- 9759047
TI  - Soft tissue injuries received during motor vehicle accidents.

PMID- 9759048
TI  - Cementable mechanics and implant dentistry.

PMID- 9759049
TI  - Radiographic/surgical template incorporating metal telescopic tubes for accurate
      implant placement.
AB  - The dental literature is replete with information on various implant surgical
      template designs and imaging techniques for presurgical assessment of dental
      implant sites. Seldom are these two aspects combined in a practical and effective
      manner to fabricate a guide for precise implant placement. Unless detailed, three
      dimensional images of the underlying bone are obtained, the use of a template is
      ineffective. This article describes a radiographic/surgical template that
      utilizes a series of telescoping metal tubes as radiographic markers and as
      implant drill guides.

PMID- 9759050
TI  - Fifty years on: does the NHS still need dentistry.

PMID- 9759051
TI  - A study of young people's perceptions of their orthodontic need and their
      experience of orthodontic services.
AB  - A study investigating young people's perceptions of their orthodontic needs,
      demands and their experience of orthodontic services was conducted in Walsall and
      Dudley health districts, using a self-completed questionnaire. The subjects were
      4812 individuals in year 10 of education (average age 15.0 years). Overall, the
      level of malocclusion perceived by the young people was similar to that
      identified by dentists in the 1993 national survey of children's dental health.
      The level of reported malocclusion by boys and girls, white and non-white
      students and students from the two districts was the same; however fewer students
      from the less prosperous neighborhoods reported having straight teeth, and more
      non-white students with irregularities wanted to have straight teeth. Although
      many young people reported having a malocclusion, the majority were not concerned
      about it. The study revealed significant differences in experience of treatment.
      Boys, non-white students and students from less prosperous areas were less likely
      to report having active orthodontic treatment. Access to specialist services was
      lower for the non-white students and students from less prosperous areas. A
      higher proportion of students treated with fixed appliances reported straight
      teeth after treatment than those treated by extractions alone or by removable
      appliance therapy.

PMID- 9759052
TI  - A clinical audit project. Record-keeping of patient status and monitoring.
AB  - This paper describes an audit of record-keeping of key information that needs to
      be readily available to assist in the delivery of a high standard of patient
      care. It resulted in the development of adhesive forms to be affixed to the front
      of the patient's record card. The use of these forms is described and
      illustrated.

PMID- 9759053
TI  - MGDS case presentation: hypodontia with retained deciduous teeth.
AB  - This case, which was presented as a log diary for the 1997 Diploma of Membership
      in General Dental Surgery (MGDS) examination, describes the examination,
      treatment planning, and subsequent treatment of a patient displaying mild
      hypodontia with retained deciduous teeth and lateral excursions guided by group
      function. It incorporates preventive treatment and management of early
      interproximal caries, prerestorative orthodontics, reorganisation to a canine
      guided occlusion using conventional and adhesive cast restorations, and
      management of an occasional clenching habit.

PMID- 9759054
TI  - The MGDS examination: a systematic approach. 3. Part II of the examination:
      diagnosis, treatment planning, execution of treatment, maintenance and appraisal,
      writing-up log diaries.
AB  - This paper is the third 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- 9759055
TI  - A survey of the views of vocational dental practitioners on continuing
      professional education.
AB  - The Faculty of General Dental Practitioners (UK) has been leading the debate on a
      career pathway in general dental practice for a number of years. Little work has
      been done to establish the views of young dentists on the ideas behind a career
      pathway and on vocational training. This paper describes a questionnaire survey
      of 77 recently qualified dentists in the Thames region. The results show that
      there is great satisfaction with vocational training (76.4%) among the
      respondents even if it were not compulsory, that the majority would not welcome a
      summative examination at the end of a two-year training period and that nearly
      all thought it was right that postgraduate education for dentists should be
      compulsory. Of respondents 66% felt that dentists with postgraduate
      qualifications should be given a higher salary while over 70% felt that
      specialisation would become more important in the future. Young dentists are very
      much in favour of postgraduate education but do not want a rigid career pathway
      laid down for them.

PMID- 9759056
TI  - From need-based to want-based dentistry: redefinition of a profession.

PMID- 9759057
TI  - Two-year performance of glass-ceramic insert-resin composite restorations:
      clinical and scanning electron microscopic evaluation.
AB  - OBJECTIVE: This study evaluated the 2-year clinical performance of beta-quartz
      resin composite restorations. METHOD AND MATERIALS: Twenty-two glass insert-resin
      composite restorations were placed. Restorations were placed in 6 molars, 12
      premolars, and 4 incisors. After 2 years, clinical assessment of the restorations
      was made by three operators according to the US Public Health Service criteria.
      Scanning electron microscopic evaluations were made by replica technique.
      RESULTS: Nineteen restorations were graded Alfa and three restorations were
      graded Bravo for color match. Twenty-one restorations were graded Alfa and one
      restoration Charlie for proximal contact, marginal integrity, and anatomic form.
      None of the restorations showed marginal discoloration, tooth sensitivity, or
      caries. CONCLUSION: Glass-ceramic insert-resin composite restorations exhibited
      excellent performance after 2 years of clinical service.

PMID- 9759058
TI  - An in vitro and in vivo evaluation of various implant-cleaning instruments.
AB  - OBJECTIVE: The surface roughness caused by four implant scalers (Premier/Hawe
      Neos, Advanced Implant Technologies, Hu-Friedy, and Nobel Biocare) on a titanium
      abutment was assessed in a standardized in vitro situation, and operators were
      asked to evaluate the clinical usefulness of each instrument. METHOD AND
      MATERIALS: Twenty-four evaluators scored scanning electron micrographs of
      abutment surfaces scaled for 15 minutes with each instrument. Twelve operators
      used each instrument on at least three implant recall patients and scored each
      for ease of access; efficacy in deposit removal; overall convenience; distance
      reached subgingivally; scaling time per abutment; and overall preference.
      RESULTS: The Advanced Implant Technologies scaler created a significantly rougher
      surface than all other instruments. The Premier/Hawe-Neos and Advanced Implant
      Technologies instruments were significantly preferred in most categories by the
      operators. There was no statistically significant difference in scaling time per
      abutment. CONCLUSION: The Premier/Hawe-Neos instrument combines operator
      acceptance with less damage to the abutments, and, of the instruments tested, is
      the scaler of choice.

PMID- 9759059
TI  - Cicatricial pemphigoid (benign mucous membrane pemphigoid).
AB  - Cicatricial pemphigoid is a chronic mucocutaneous bullous condition. It is a
      heterogenous autoimmune disease, characterized by the production of
      autoantibodies against basement membrane zone antigens. The target antigens in
      cicatricial pemphigoid appear to be lamina lucida proteins involved in human
      keratinocyte adhesion to extracellular matrix. Cicatricial pemphigoid primarily
      affects persons older than 40 years and appears to have a 2:1 predilection for
      women, without racial or geographic bias.

PMID- 9759060
TI  - Gingival involvement in mucous membrane pemphigoid.
AB  - A 60-year-old woman with clinical features of desquamative gingivitis had a
      history of painful, blistering gingival lesions for more than 2 years. There were
      no other accompanying mucosal or skin lesions. Clinical examination revealed
      erythematous and edematous gingiva with ulcerated areas and evidence of intact
      and ruptured bullae. White plaquelike lesions were also noted. Gingival
      manipulation caused epithelial desquamation. Light microscopic examination of
      biopsy specimens from the perilesional gingival tissue showed separation of the
      oral gingival epithelium and connective tissue at the margin of the collapsed
      bulla. A moderately intense inflammatory infiltrate was present in the connective
      tissue. Direct immunofluorescent microscopy revealed a continuous linear
      deposition of immunoglobulin G and C3 at the basement membrane zone. On the basis
      of clinical, histopathologic, and immunofluorescent findings, the diagnosis of
      mucous membrane pemphigoid was made.

PMID- 9759061
TI  - The effectiveness and side effects of 0.1% and 0.2% chlorhexidine mouthrinses: a
      clinical study.
AB  - OBJECTIVE: The study compared two commercial chlorhexidine mouthrinses
      (Chlorhexamed 0.1% and Corsodyl 0.2%) for their effects on dental plaque and
      gingival inflammation, their side effects (eg, tooth staining and mucosal
      irritation), and patient acceptance. METHOD AND MATERIALS: One hundred thirty
      healthy volunteers were randomly distributed into two groups of 65 each. Each
      volunteer had gingivitis or chronic marginal periodontitis and used the rinse two
      times a day for 4 weeks. The sulcular bleeding index, approximal plaque index,
      gingival index, and a discoloration index were taken at baseline and once a week
      thereafter. The patients were questioned about taste disturbances, mucosal
      irritation, and their perception of the taste of the mouthrinse. RESULTS: In both
      groups, after 4 weeks, the mean sulcular bleeding index, approximal plaque index,
      and gingival index scores had decreased significantly. The discoloration index
      had increased significantly in both groups. There were no statistically
      significant differences between the two mouthrinses in any of these measurements.
      There were no significant differences in side effects reported by the two groups.
      CONCLUSION: The increase in concentration of chlorhexidine provided no clinical
      advantages or disadvantages.

PMID- 9759062
TI  - Nightguard vital bleaching removes brown discoloration for 7 years: a case
      report.
AB  - Nightguard vital bleaching with 10% carbamide peroxide was used to remove a brown
      stain from the maxillary central incisor of a 13-year-old-boy. After 7 years,
      during which there was no touch-up treatment, the discoloration had not returned.
      This conservative technique should be considered before more invasive procedures
      for the treatment of discolored vital teeth in young patients.

PMID- 9759063
TI  - Family violence prevention: dentistry's attitudes and responsibilities.

PMID- 9759064
TI  - Oral condyloma acuminatum as an indicator of sexual abuse: dentistry's role.

PMID- 9759065
TI  - Abuse detection in the dental environment.

PMID- 9759066
TI  - Helmut Heydt--a man for all seasons.

PMID- 9759067
TI  - Helmut Heydt, a man with a heart to resolve, a head to contrive, and a hand to
      execute.

PMID- 9759068
TI  - Helmut Heydt and the unpublished after dinner speech.

PMID- 9759069
TI  - The Prosthodontic Society of South Africa. Its origin and history.

PMID- 9759070
TI  - Helmut Heydt and the Professional Provident Society.

PMID- 9759071
TI  - The role played by the College of Medicine of South Africa in dentistry.

PMID- 9759072
TI  - [Drinking behavior of the elderly. Always drink an extra glass].

PMID- 9759073
TI  - [Burnout syndrome. From idealism to ... exhaustion].

PMID- 9759074
TI  - [Accidents are rarely accidental].

PMID- 9759075
TI  - [Shedding light on the gray zone of nursing activities].

PMID- 9759076
TI  - [In the confines of anorexia].

PMID- 9759077
TI  - [Therapeutic project: intensive treatment: crisis situations].

PMID- 9759078
TI  - [The ice was broken].

PMID- 9759079
TI  - [Program of accelerated convalescence after major surgery. Promising results].

PMID- 9759080
TI  - [Dealing with a patient's violence. Tying the patient down].

PMID- 9759081
TI  - [Education at the Morges Nursing School under the eyes of the employers. The
      formula works].

PMID- 9759082
TI  - [A dignified anniversary celebration. Rive Neuve; 10 years].

PMID- 9759083
TI  - [Teaching research in Haiti. Awareness begins at the base].

PMID- 9759084
TI  - [Encounter with the mask].

PMID- 9759085
TI  - Cost constraints and GME program size.

PMID- 9759086
TI  - Locating conference paper.

PMID- 9759087
TI  - AHC--community partnerships for interdisciplinary education.

PMID- 9759088
TI  - The bonsai master.

PMID- 9759089
TI  - The "John McCain Rap": a metaphor for domestic violence.

PMID- 9759090
TI  - Achieving better institutional self-study.

PMID- 9759091
TI  - Home care--the time to teach about it is now.

PMID- 9759092
TI  - Where is the "gene" in the generalist literature?

PMID- 9759093
TI  - Encourage qualitative research to improve students' clinical skills!

PMID- 9759094
TI  - Emerging lessons of the Interdisciplinary Generalist Curriculum (IGC) Project.
AB  - The Interdisciplinary Generalist Curriculum Project (IGC) was funded in 1993 by
      the Health Resources and Services Administration with the goal of developing
      innovative preclinical generalist curricula in ten of the nation's medical and
      osteopathic schools. The IGC successfully completed two competitive cycles in
      which ten schools were awarded three-year contracts. Although the long-term goal
      of the project is to increase the proportion of medical students choosing
      generalist careers, much has been learned thus far about the processes of
      curricular change and interdisciplinary cooperation. Drawing on information from
      school reports, site visits, external evaluations, academic presentations, and
      annual project meetings, this report presents the emerging lessons learned in the
      key areas of interdisciplinary collaboration, recruitment and retention of
      community preceptors, faculty development, and integration of generalist-related
      components into the four-year medical school curriculum. These lessons should
      prove useful for other schools embarking upon significant curricular innovations.

PMID- 9759095
TI  - Understanding the costs of ambulatory care training.
AB  - While patient care has been shifting to the ambulatory setting, the education of
      health care professionals has remained essentially hospital-based. One factor
      discouraging the movement of training into community-based ambulatory settings is
      the lack of understanding of what the costs of such training are and how these
      costs might be offset. The authors describe a model for ambulatory care training
      that makes it easier to generalize about to quantify its educational costs. Since
      ambulatory care training does not exist in a vacuum separate from inpatient
      education, the model is compatible with the way hospital-based education costs
      are derived. Thus, the model's elements can be integrated with comparable
      hospital-based training cost elements in a straightforward way to allow a total
      costing approach. The model is built around two major sets of variables affecting
      cost. The first comprises three types of costs--direct, indirect, and
      infrastructure--and the second consists of factors related to the training site
      and factors related to the educational activities of the training. The model is
      constructed to show the various major ways these two sets of variables can
      influence training costs. With direct Medicare funding for some ambulatory
      setting-based education pending, and with other regulatory and market dynamics
      already in play, it is important that educators, managers, and policymakers
      understand how costs, the characteristics of the training, and the
      characteristics of the setting interact. This model should assist them. Without
      generalizable cost estimates, realistic reimbursement policies and financial
      incentives cannot be formulated, either in the broad public policy context or in
      simple direct negotiations between sites and sponsors.

PMID- 9759096
TI  - Moving a graveyard: how one school prepared the way for continuous curriculum
      renewal.
AB  - From 1991 to 1996, the faculty at the University of Florida College of Medicine
      initiated several significant changes in its curriculum. These changes, included
      the introduction of early clinical experience in primary care settings; the
      enhancement of active learning experiences in small-group settings; production
      and use of computer-based interactive learning materials; increased clinical
      teaching in the ambulatory care training in an interdisciplinary primary care
      clerkship; effective course and faculty evaluation; establishment and use of an
      assessment center for instruction and performance-based evaluations utilizing
      standardized patients; creation of a medical education center as the focal point
      for logistics support of the teaching faculty and education data handling;
      creation of a faculty development program; and initiation of mission-based
      budgeting based on the faculty's teaching effort and quality. Because the faculty
      were relatively conservative, it was important to identify variables that would
      facilitate the introduction of changes and those that might hinder it. The
      following factors were most important: interest and support by the dean and
      clearly defined delegation of authority to an associate dean; introduction of a
      mission-based budgeting process that allocates education funds on the basis of
      faculty teaching effort and its quality; a clear understanding of the empowerment
      of the curriculum committee; and an identification of the principles that should
      guide educational planning and implementation. These efforts are considered the
      beginning of the continuous renewal needed to respond to information networking,
      scientific and technological innovations, and the fundamental changes in health
      care delivery. As these changes have taken place, a shift toward greater
      institutional control of the educational program leading to the MD degree has
      been evident.

PMID- 9759097
TI  - Forum on the future of academic medicine: session IV--the realities of the health
      care environment.
AB  - At the fourth meeting of the AAMC's Forum on the Future of Academic Medicine in
      December 1997, Dr. Paul Griner and Dr. David Blumenthal discussed findings from
      their in-depth case studies of how ten academic medical centers (AMCs) were
      responding to the changing, more competitive marketplace and what these AMCs were
      doing to sustain the missions of their medical schools and teaching hospitals.
      Rapid, wide-ranging internal changes are taking place, such as centralizing
      management, down-sizing operations, partnering or merging with other schools or
      hospitals, revising legal relationships to state governments (for public schools
      and hospitals), creating independent corporations, and increasing alliances with
      industry. But AMCs will not be able to sustain their vital balancing act between
      academia and the health care system unless they can develop ways that both enlist
      faculty to meet the demands of the marketplace and also protect academic
      productivity. Reforms in faculty governance are taking place, dealing especially
      with issues of reciprocal AMC-faculty accountability. Robert Z. Gussin, vice
      president for science and technology of Johnson & Johnson, then spoke concerning
      how his vast company was dealing with changing conditions, and discussed the
      relationships, roles, opportunities, and problems of academia and industry in
      carrying out pharmaceutical research. Members then discussed the future of
      biomedical research funding, which was seen as being reasonably stable and a
      beneficiary of industry's partnering with AMCs and increased federal support. The
      meeting closed with a continuation of an earlier meeting's inquiry about the
      characteristics of the ideal medical school in the next century and what barriers
      would be faced in reaching this ideal. The group agreed again that service to
      society should remain schools' major goal, and they described and discussed
      several barriers to change, many of them internal. The group had a number of
      suggestions about dealing with the barriers, but there was no consensus. The
      members did agree, however, that the forum discussions are worthwhile, and one
      participant urged that in planning for the future the AAMC broaden its agenda,
      since the core values of medicine, nursing, and public health all relate to the
      AAMC's mission.

PMID- 9759098
TI  - The evolving duty to disclose the presence of genetic disease to relatives.
AB  - Under the aegis of the Human Genome Project, research laboratories are
      identifying the genetic bases of human diseases almost daily. This explosion in
      molecular biology has raised many medical-legal issues about genetic information,
      such as privacy, discrimination, and insurability. Less appreciated is another
      issue that faces physicians who deal with genetic information in their practices-
      their duty to disclose a genetic disease to relatives of their patients who have
      the disease. Few cases have addressed the issue directly, and there has been
      little statutory and policy development in this area. However, because a
      physician's diagnosis of a genetic disease could have such a profound impact on
      the patient's relatives, there is a developing duty to consider disclosing
      genetic information to relatives. The case law and policy that support such
      disclosure reflect the evolution of medicine and the law away from paternalism
      toward an expanded concept of legal and moral duty. Since genetic information is
      presumed to be confidential by the law, as is essentially all medical
      information, guidelines need be developed regarding a physician's duty to
      disclose a genetic disease to a patient's relatives. These guidelines should
      consider the patient, the genetic test, the disease, and the third-party
      relative. Disclosure should be considered for a disease that is serious or fatal,
      treatable or curable, and transmitted dominantly with high penetrance. Specifics
      notwithstanding, these policies should be developed by physicians who care for
      patients and their families, not by lawyers and ethicists with no clinical
      training.

PMID- 9759099
TI  - Developing curricula in spirituality and medicine.
AB  - In recent years patients and some members of the medical community have expressed
      the concern that doctors have forgotten about compassion and too often ignore
      their patients' spiritual concerns. Patients can and should expect their
      physicians to respect their beliefs and be able to talk with them about spiritual
      concerns in a respectful and caring manner. Medical schools must teach their
      students how to meet these expectations, and health care systems need to provide
      practice environments that foster compassionate caregiving. Medical educators are
      recognizing the need to bring the art of compassionate caregiving back into the
      medical school curriculum. This paper focuses on one approach to achieving this
      goal, the study of spirituality and medicine. The authors discuss the
      relationship of spirituality and healing, and describe studies that have shown
      patients' desire to have spiritual issues addressed by their physicians and the
      potential health benefits of spiritual beliefs. Finally, they describe common
      elements of the spirituality courses offered by approximately 50 U.S. medical
      schools, including 19 schools that have been awarded grants from the National
      Institute for Healthcare Research for the development of curricula in
      spirituality and medicine.

PMID- 9759100
TI  - Managing information technology in academic medical centers: a "multicultural"
      experience.
AB  - Based on a session at the 1997 conference on Information Resources and Academic
      Medicine sponsored by the Association of American Medical Colleges, this article
      illustrates how the beliefs and concerns of academic medicine's diverse
      professional cultures affect the management of information technology. Two
      scenarios--one dealing with the standardization of desktop PCs, the other with
      publication of syllabi on an institutional intranet--form the basis of this
      exercise. Four prototypical members of a hypothetical medical center community-
      the chairman of surgery, a senior basic scientist, the chief information officer
      of an affiliated hospital, and the chief administrative officer--offer their
      perspectives on each scenario. Their statements illustrate many of the challenges
      of planning, deploying, and maintaining effective information technology in the
      "multicultural" environment of academic medical centers.

PMID- 9759101
TI  - Medicine and the arts.

PMID- 9759102
TI  - Rethinking medical education through injury control.

PMID- 9759103
TI  - Minority students, affirmative action, and the admission process: a survey of 15
      medical schools.
AB  - PURPOSE: To assess the current state of admission policies for underrepresented
      minorities (URMs) at medical schools. METHOD: In 1997, the author surveyed the
      admission directors at the 15 medical schools with the largest URM populations.
      The four categories in the questionnaire covered the makeup of the admission
      committee, the weights given quantitative factors in admission decisions, the
      weights given qualitative factors, and the weight given the applicant's status as
      a URM or disadvantaged student. RESULTS: The 12 responding admission directors
      provided a wide range of answers as to the makeup of the admission committee and
      the weights assigned quantitative and qualitative factors. None of the schools
      gave an exact percentage weight to URM status, although one school added points
      to a diversity index, which was then used as a quantitative measure. There
      appears to be an increasing focus on economic and educational disadvantage.
      CONCLUSIONS: The limited parameters of the study prevent the author from offering
      definitive solutions. However, the responses to the survey suggest that admission
      policies are secretive and widely varied. The academic community must consider
      the reasons behind and the consequences of abandoning a forthright approach to
      affirmative action.

PMID- 9759104
TI  - Comparing the psychometric properties of checklists and global rating scales for
      assessing performance on an OSCE-format examination.
AB  - PURPOSE: To compare the psychometric properties of checklists, global rating
      scales preceded by a checklist, and global rating scales alone in assessing
      surgery residents' performances on an OSCE-like technical skills examination.
      METHOD: In 1996, 53 general surgery residents with one to six years of
      postgraduate training participated in a performance-based examination of
      technical skills consisting of eight 15-minute stations (bench-model simulations
      of operative procedures in general surgery). Two qualified surgeons marked at
      each station, one using a task-specific checklist (C) and a subsequent global
      rating scale (Gc), the other using a global rating scale only (G). RESULTS:
      Interstation reliabilities measured by Cronbach's alpha were .79 for C, .89 for
      Gc, and .85 for G. A series of multiple regressions predicting level of training
      from test scores revealed an R2 of .584 for C alone, which increased to .711 when
      Gc was entered after (p < .001), and increased to .704 when G was entered after C
      (p < .001). However, R2 for Gc alone was .711, and for G alone was .704, neither
      of which changed when C was entered into the prediction (p > .10). The R2 for Gc
      and G predicting level of training (.725) was not significantly greater than that
      of either Gc or G alone. A very similar pattern of results was seen when C, Gc,
      and G were used to predict independent evaluations of the operative outcomes.
      CONCLUSIONS: Global rating scales scored by experts showed higher inter-station
      reliability, better construct validity, and better concurrent validity than did
      checklists. Further, the presence of the checklists did not improve the
      reliability or validity of the global rating scale over that of the global rating
      scale alone. These results suggest that global rating scales administered by
      experts are a more appropriate summative measure when assessing candidates on
      performance-based examinations.

PMID- 9759105
TI  - Internship ratings as a validity outcome measure for an evaluation system to
      identify inadequate clerkship performance.
AB  - PURPOSE: To determine whether a third-year clerkship evaluation system validly
      predicted students' later performance ratings during their internships. METHOD:
      Adequacy of students' clerkship performances and the need for remediation were
      determined during seven consecutive academic years at the Uniformed Services
      University of the Health Sciences F. Edward Hebert School of Medicine using a
      criterion-based process including formal evaluation sessions. Internship ratings
      of students who needed remediation (remediators) from 1986 to 1993 were compared
      with those of students who voluntarily chose fourth-year medicine (non
      remediators). Using written questionnaires, internship directors rated the
      graduates on a five-point scale for fund of knowledge, attitude, and analytic
      ability, and also provided written comments. RESULTS: Responses to questionnaires
      were available for 75 of 97 remediators (78%) and 268 of 313 non-remediators
      (86%). The remediators were 12.9 times more likely to have low internship
      performance scores and 9.4 times more likely to receive unfavorable comments than
      were the non-remediators. However, the majority of the remediators (80%) received
      only favorable comments. The medicine clerkship grade was more sensitive than the
      non-medicine grade-point average in predicting problems during internship (75% vs
      8%). CONCLUSION: The medicine clerkship evaluation process detected whether a
      student was likely to have problems during internship, and the internship ratings
      supported the predictive validity of the evaluation system. The majority of
      students who were successfully remediated had no identifiable problems during
      internship.

PMID- 9759106
TI  - Physicians' and medical students' perspectives on patients' quality of life.
AB  - PURPOSE: To compare medical students' and oncologists' perspectives about patient
      related quality of life (QOL). METHOD: In 1996, the authors compared the
      questionnaire responses of 65 oncologists and 105 medical students in the state
      of Hawai'i. RESULTS: Participants returned 146 usable questionnaires (response
      rates: 69% of oncologists and 97% of students). Both groups saw pain and
      suffering as central to QOL, while medical students also valued autonomy. Both
      groups indicated that QOL was at least as important as survival in treatment
      decision making. Students were significantly more likely to emphasize the
      importance of QOL over survival. Students strongly preferred physician interviews
      to assess QOL. Most physicians reported assessing QOL in every patient, but only
      one in ten had used a QOL assessment questionnaire. CONCLUSION: Both students and
      oncologists expressed considerable interest in QOL and virtually all regarded it
      as an important part of care. There were more similarities than differences in
      responses. Future educational programs in both medical school and continuing
      education should build on these positive attitudes.

PMID- 9759107
TI  - Effect of undergraduate college major on performance in medical school.
AB  - PURPOSE: To determine whether choice of college major has any effect on
      performance in medical school. METHOD: The author analyzed data for 406 students
      enrolled in a combined baccalaureate-MD program at Brown University School of
      Medicine who had matriculated in medical school from 1989 to 1997, determining
      their undergraduate majors and their medical education performances (as measured
      by course grades, USMLE, scores and residency program evaluation). RESULTS:
      Slightly over half of the students had majored in science or mathematics, about a
      third had majored in the humanities or social sciences, and about a tenth had had
      double majors or had been independent concentrators. The author found no
      statistically significant difference between the medical school performances of
      students who had majored in the sciences or mathematics and those who had majored
      in the humanities or the social sciences. CONCLUSION: Although preselection bias
      may influence medical school performance, this study affirms previous findings
      that choice of undergraduate major has little, if any, statistically significant
      effect.

PMID- 9759108
TI  - The costs versus the perceived benefits of an LCME institutional self-study.
AB  - PURPOSE: To calculate the costs versus the perceived benefits of an institutional
      self-study done to satisfy the requirements of the Liaison Committee on Medical
      Education's (LCME's) accreditation process. METHOD: From postcard questionnaires,
      the authors determined the hours spent over 18 months from 1994 to 1996 on the
      institutional self-study by 131 self-study committee members and 64 database
      compilers at the Medical College of Wisconsin. The committee members also rated
      the potential utility of the self-study process and the probability that the
      concerns identified by their subcommittees would be addressed. Administrative
      costs (self-study coordinating team's hours, supplies, and other expenses) were
      tracked using calendars and budget subaccount numbers. Personnel costs were
      calculated using salary data from the Association of American Medical Colleges
      and the College and Universities Personnel Administrators' survey. RESULTS:
      Supplies and equipment for the self-study cost $12,158, and the personnel costs,
      based on an 81% response rate, were estimated at $207,384, for a total of
      $219,542. The participants in the self-study rated the process as moderately
      useful, but believed that there was only a medium degree of probability that
      concerns they had identified would be addressed. CONCLUSION: Considering the
      costs of self-study, the process might be more useful if attention were focused
      less on identifying concerns and more on an institution's demonstrated ability to
      successfully respond to problems.

PMID- 9759109
TI  - Do clinical breast examination skills improve during medical school?
AB  - PURPOSE: To assess the effects of stage of training, gender, and specialty
      interest on medical students' breast cancer knowledge, attitudes, and clinical
      breast examination (CBE) skills as a case study of the progression of physical
      examination skills during medical education. METHOD: In 1996, questionnaires
      assessing breast cancer knowledge and attitudes were administered to 493
      premedical and first-, second-, and third-year medical students at Northwestern
      University Medical School. Silicone breast models were used to evaluate the CBE
      proficiency of a subset of 151 students. RESULTS: Breast cancer knowledge was
      positively correlated with stage of training (r = .62), with significant
      differences between all levels (p < .001). In contrast, first-year medical
      students attained the highest mean lump-detection sensitivity (61.5%), followed
      by second-year (53.9%) and third-year (43.5%) students (p < .001, first- vs third
      year students; p < .10, second- vs third-year students). There was no significant
      difference in specificity among the four stages. CONCLUSIONS: The results suggest
      that breast cancer knowledge and attitudes are not related to CBE proficiency,
      which is a practiced tactile skill. The decline in lump-detection sensitivity
      with increased stage of training may demonstrate the need for increased attention
      to palpation skills during the clinical years. These findings are consistent with
      those of earlier reports that suggest the need for the reinforcement of physical
      examination skills during clinical education.

PMID- 9759110
TI  - Medical education: can we do better?

PMID- 9759111
TI  - A story of change.
AB  - In this introduction to Issues and Strategies for Reform in Medical Education:
      Lessons from Eight Medical Schools, the authors describe the overall objective of
      the supplement, which is to present the qualitative reflections of 12 faculty
      members at eight medical schools who worked to reform their schools' curricula as
      part of The Robert Wood Johnson Foundation's "Preparing Physicians for the
      Future: A Program in Medical Education." They outline the issues addressed in the
      reform efforts at all of the eight schools, including health promotion/disease
      prevention and ambulatory care, the editors' choice of a "vignette-based" format
      for the chapters, and the content of the three appendices that end the
      supplement. They conclude with a brief description of the lessons learned by all
      participants in the collaborative effort of producing this supplement on
      curriculum change.

PMID- 9759112
TI  - The process of change: stories of the journey.
AB  - This chapter provides an overview of the decisions, activities, events, and
      issues that influenced the process of change at the eight schools that
      participated in The Robert Wood Johnson Foundation's "Preparing Physicians for
      the Future: Program in Medical Education." The author focuses in particular on
      three stages of the change process: planning and creating the climate for change,
      making the change, and reinforcing the new model. She describes the different
      strategies the schools used to work through these stages (in some cases, several
      iterations of these stages) and the common lessons participants learned about how
      to successfully implement curricular reforms.

PMID- 9759113
TI  - Leadership and governance.
AB  - In this chapter, the author discusses leadership and governance issues in
      implementing curricular reform at the eight schools that participated in The
      Robert Wood Johnson Foundation's "Preparing Physicians for the Future: Program in
      Medical Education." Leadership is defined as the roles played by key individuals
      within a school in facilitating significant curricular change; institutional
      governance is the administrative structure through which the curricular changes
      were administered. The characteristics of successful leaders as well as problems
      caused by poorly chosen leaders are described. The author also discusses how
      leaders handled resistance to change and the role of students in overcoming this
      resistance at some institutions. The second half of the chapter focuses on
      governance structures. The author briefly discusses the role of curriculum
      committees, how student and faculty committees at some schools worked to
      implement change, and the implementation at each of the eight schools of a
      centralized education budget. He concludes with a list of characteristics of
      successful leadership and successful governance in the process of curriculum
      reform.

PMID- 9759114
TI  - Communication and the process of educational change.
AB  - In this chapter, the authors describe the role of communication in the process of
      curricular reform at the eight schools that participated in The Robert Wood
      Johnson Foundation's "Preparing Physicians for the Future: Program in Medical
      Education." The collective experience of these eight schools suggests that
      despite its general neglect in the discourse on educational innovation, good
      communication is a decisive element of any successful reform initiative. The
      authors focus this chapter on effective communication patterns for supporting
      educational reform. First, the authors discuss a four-stage model of change-
      recognizing the need for change, and planning, implementing, and
      institutionalizing change--and describe the role of communication in each of
      them. They outline the communication strategies needed to promote a sense of
      ownership among all participants; structures and mechanisms for supporting
      positive communication; and common lessons learned by all schools about
      successful communication.

PMID- 9759115
TI  - Integrating the teaching of basic sciences, clinical sciences, and
      biopsychosocial issues.
AB  - In this chapter, the author describes integrating the teaching of the basic
      sciences, clinical sciences, and biopsychosocial issues in medical education as
      part of the curricular reform efforts initiated by schools that participated in
      The Robert Wood Johnson Foundation's project "Preparing: Physicians for the
      Future: Program in Medical Education." The author focuses on the approaches the
      eight schools adopted, the challenges they encountered, and the lessons they
      learned in attempting to implement more integrated curricula. Integration was
      promoted both within and among various components of medical education. For
      example, in some cases discipline-based courses in the basic sciences were
      replaced with interdisciplinary courses. Further, efforts were made both to bring
      clinical relevance to the basic sciences and to strengthen basic science in the
      clinical years. All the schools also promoted the study of the humanities and
      biopsychosocial sciences throughout the curriculum. The author describes problems
      encountered in these endeavors, resources needed to support interdisciplinary
      courses, the benefits of integration, and common lessons learned by the eight
      schools.

PMID- 9759116
TI  - Faculty development: a field of dreams.
AB  - This chapter describes the faculty development efforts of the eight schools that
      participated in The Robert Wood Johnson Foundation's "Preparing Physicians for
      the Future: Program in Medical Education." The authors define "faculty
      development" as the "enhancement of educational knowledge and skill of faculty
      members so that their educational contributions can extend to advancing the
      educational program rather than just teaching within it." Faculty development
      programs varied widely among the schools. Some schools had active programs in
      place, others initiated programs at the start of the project. This chapter
      explores the faculty development topics and methods, both shared and unique,
      among the eight schools. It then looks at the ways the schools motivated their
      faculties to participate in their programs. Finally, it describes some of the
      outcome measures that were used to gauge the effectiveness of the faculty
      development programs. The authors conclude that the eight schools' approaches and
      levels of commitment to their faculty development programs varied. They present
      lessons learned from the successes and failures of the various programs.

PMID- 9759117
TI  - Instructional methods.
AB  - This chapter addresses one of the goals of The Robert Wood Johnson Foundation's
      "Preparing Physicians for the Future: Program in Medical Education" grants: to
      introduce new methods of instructions along with curricular revisions. Methods of
      instruction emphasize "how to teach," in contrast to the curricular reform's
      "what to teach." The author explores the various ways in which the eight
      participating schools adopted new instructional methods. The author first sets
      out the conditions for effective learning, as expressed in earlier research in
      cognitive psychology. He then reviews the issues in new instructional methods:
      problem-based learning, small-group learning, self-directed learning, and
      instructional methods in the service of integration, as well as learning in
      outpatient settings and computer-based learning. The author concludes, among
      other things, that schools must respect the variety of ways in which students
      learns, that some faculty will have to become skilled in unfamiliar teaching
      methods, that new instructional methods should be based on empirical evidence of
      effectiveness, and that sometimes method may be less important than the skill and
      enthusiasm of the teacher.

PMID- 9759118
TI  - Student assessment.
AB  - This chapter looks at changes in assessing medical students implemented by the
      eight schools participating in The Robert Wood Foundation's "Preparing Physicians
      for the Future: Program in Medical Education." The eight schools took a variety
      of approaches, some working incrementally, others making large, cross
      departmental changes. Each school's support for or constraints to change
      influenced its approach in assessment. The authors describe the ways in which
      students were assessed within their courses and clerkships. They look at specific
      forms of assessment, such as self-assessment, feedback, and standardized-patient
      assessment. For most of the schools, changes in student assessment were
      controlled by course or clerkship directors and managed by faculty. Often,
      changes in assessment came after changes in curriculum. Changes were easier to
      make in the first two years of medical school than in the clinical years. The
      authors also discuss the integration of assessment within the curriculum,
      comprehensive performance-based assessments, and situations where change in
      assessment did not occur. They discuss the politics of change, and offer a
      summary of the eight schools' assessment experiences and the lessons learned.

PMID- 9759119
TI  - Evaluating change in medical school curricula: how did we know where we were
      going?
AB  - This chapter compares and contrasts the primary outcomes and methods used to
      evaluate the curricular changes at the eight schools participating in The Robert
      Wood Johnson Foundation "Preparing Physicians for the Future: Program in Medical
      Education." Each school evaluated its own program. The eight evaluators formed an
      ad hoc group to share information, but the schools did not use a common
      evaluation system. Although the evaluations were done without common standards,
      many of the measures were similar. The schools used such quantitative methods as
      measuring students' performances and their choices of specialties, as well as
      such qualitative methods as asking students to evaluate their courses and to
      participate in focus groups. The authors describe the ways in which evaluative
      data were collected and how evaluation drove curricular change. The authors
      conclude that program evaluation can sustain schools through the turbulence of
      curricular change, and that qualitative data and communicating the results of
      evaluations with faculty and students are essential to successful reform.

PMID- 9759120
TI  - Reflections on relevance, resistance, and reform in medical education.
AB  - This chapter reflects upon the collective experiences of the eight schools
      participating in the Robert Wood Johnson Foundation's "Preparing Physicians for
      the Future: A Program in Medical Education," highlighting the lessons learned
      over the five years of the program. The authors set the context and give a short
      history of the program. They discuss the ways in which the processes of change
      occurred at the eight schools, commenting on issues of leadership, governance,
      communication, faculty development, integration, instructional methods, student
      assessment, and program evaluation (all of which received lengthier treatment in
      earlier chapters). The authors conclude that changes in all of these areas are
      necessary for successful reform of medical education.

PMID- 9759121
TI  - Radiography and bone scintigraphy in osteoarthritis of the knee--comparison with
      MR imaging.
AB  - PURPOSE: Osteoarthritis (OA) is a multifactorial process affecting cartilage and
      subchondral bone. Traditionally, plain radiographs and eventually bone
      scintigraphy are used to establish the diagnosis, whereas MR imaging, as a
      sensitive instrument for early diagnosis, is less commonly used. Therefore, these
      methods have been compared in the format of a prospective study of knee OA.
      MATERIAL AND METHODS: Individuals aged 35-54 years with chronic knee pain have
      been identified. The prevalence of chronic knee pain was 15% (279/2,000). Within
      this group, both knees in 61 randomly chosen persons were examined with plain
      weight-bearing radiographs of the tibiofemoral joint (TFJ), standing axial
      radiographs of the patellofemoral joint (PFJ), and with bone scintigraphy. One
      knee (the most painful at inclusion in the study) in each person was examined
      with MR imaging on a 1.0 T imager. RESULTS AND CONCLUSIONS: Assessment of the
      minimal joint space (MJS) width in the p.a. view of the TFJ in weight-bearing
      examinations should be performed with equal weight on both legs and in
      semiflexion. The p.a. view of the TFJ and the axial view of the PFJ, as well as
      the MJS measurements in these views, were reproducible. MJS of 3 mm in the TFJ
      and MJS of 5 mm in the PFJ are limits in diagnosing joint-space narrowing (JSN)
      in the TFJ and the PFJ, respectively. There was a high prevalence of meniscal
      abnormalities within the narrowed compartments of the TFJ when compared with
      those that were not narrowed. With the presence of marginal osteophytes in the
      TFJ, there was a high prevalence of MR-detected cartilage defects in the same
      joints whether JSN (MJS < 3 mm) was present or not. No such relationship,
      independent of MJS, was found between marginal osteophytes and cartilage defects
      in the PFJ. The agreement between increased bone uptake and MR-detected
      subchondral lesion (increased signal in the STIR sequence) was good. The
      agreement between increased bone uptake and MR-detected osteophytes or cartilage
      defects was in general poor. Conventional radiography is inexpensive and readily
      available. With the increased knowledge about interpreting weight-bearing p.a.
      radiographs of the TFJ and standing axial radiographs of the PFJ, these
      examinations will, even in the future, be a valuable and competitive technique
      compared with a more expensive and sophisticated method such as MR imaging, when
      evaluating knee pain. Further studies have to be performed to evaluate whether MR
      imaging has the same ability as bone scintigraphy to predict the progression of
      the OA process in the knee joint.

PMID- 9759122
TI  - American College of Rheumatology 62nd National Scientific Meeting and Association
      of Rheumatology Health Professionals 33rd National Scientific Meeting. San Diego,
      California, USA. November 8-12, 1998. Abstracts.

PMID- 9759123
TI  - Why do women have rheumatic disease?
AB  - If gonadal hormones are responsible for the female predominance (gender
      discrepancy, sexual dimorphism) that characterizes most autoimmune rheumatic
      diseases, pregnancy should be a particularly vulnerable period for onset of new
      disease as well as for exacerbation of established disease. Currently available
      data support neither the contention: that pregnancy increases incidence nor that
      it worsens severity of the common illnesses. Moreover, many illnesses
      pathogenetically similar to rheumatic diseases have the same hormonal background
      but are not characterized by sexual dimorphism. In nonrheumatic sexually
      dimorphic illnesses an environmental, behavioral, or genetic reason for gender
      discrepancy is usually present. To explain sexual dimorphism in the autoimmune
      rheumatic diseases, the fields of environmental, genetic, chromosomal, and in
      utero sex differentiation need further exploration.

PMID- 9759124
TI  - Microchimerism and the causation of scleroderma.
AB  - The application of molecular techniques to the study of human pregnancy has
      resulted in the recognition that there is bi-directional cell traffic during
      pregnancy. Recent studies indicate fetal progenitor cells can persist in the
      maternal peripheral blood for decades after childbirth. Scleroderma is increased
      in women, has a peak incidence following childbearing years, and has clinical
      similarities to chronic graft-versus-host disease that occurs after allogeneic
      stem cell transplantation. This paper explores the idea that microchimerism is
      involved in scleroderma and considers insights gained from transplantation
      biology in seeking to understand how microchimerism might contribute to the
      pathogenesis of scleroderma. Chimerism means that a body contains cell
      populations derived from different individuals and microchimerism low levels of
      chimerism. Although highlighted in the study of scleroderma, microchimerism is
      also implicated in selected other autoimmune disorders.

PMID- 9759125
TI  - Immune modulation (TH1 and TH2 responses) in pregnancy.

PMID- 9759126
TI  - Interleukin-3 and pregnancy loss in antiphospholipid syndrome.
AB  - Cytokines play an important role in the progression of autoimmune diseases, and
      therefore it is not surprising that their levels may be altered in some of these
      diseases. Interleukin-3 (IL-3), which is an hematopoietic growth factor as well
      as an important factor that aids in embryo implantation and placental
      development, was found to be decreased both in pregnant women with
      antiphospholipid syndrome (APS) compared with a control group, and in animal
      models of APS. Treatment of animals having APS with IL-3 succeeded in prevention
      of disease manifestations. In this communication we review IL-3 and APS
      interrelationship, and discuss the role of aspirin and other commonly used drugs,
      with respect to IL-3 levels in APS.

PMID- 9759128
TI  - The effects of prolactin in animal models of SLE.

PMID- 9759127
TI  - Neonatal lupus and autoantibodies reactive with SSA/Ro-SSB/La.

PMID- 9759129
TI  - Antiphospholipid syndrome in pregnancy--animal models and clinical implications.
AB  - The antiphospholipid (APS) syndrome frequently includes severe pregnancy
      complications such as fetal wastage and recurrent spontaneous abortions. Animal
      models for APS in pregnancy can provide both an understanding of the pathogenic
      mechanisms of anti-phospholipid antibodies (aPL), and aid in the evaluation of
      various therapeutic modalities in APS. Animal models for APS include both
      spontaneously developed diseases, as is the case for secondary APS in mice with
      another autoimmune disease, and induced models of APS. The latter includes either
      passive induction of disease by antibodies infusion, or active induction via
      manipulation of the idiotypic network. This article summarizes the literature
      reports of animal models of APS in pregnancy, deal with the various possible
      mechanisms of action of aPL in pregnancy, and discuss the treatment options of
      women having pregnancy complications of APS.

PMID- 9759130
TI  - Placental pathology in systemic lupus erythematosus and phospholipid antibody
      syndrome.

PMID- 9759131
TI  - Anti-phospholipid autoantibodies--do they have a pathogenic role in infertility?
AB  - Anti-phospholipid syndrome includes a variety of clinical manifestations, among
      which is recurrent pregnancy loss. Recently, it was suggested that anti
      phospholipid antibodies might also have a role in infertility, mainly in
      unexplained infertility. Most of the studies report about an increased prevalence
      of these antibodies in infertile women; however, data regarding the implication
      of these antibodies on treatment outcome (mainly in in-vitro fertilization) and
      if there is a beneficial effect of treating these patients with aspirin, heparin
      and prednisone--remains still controversial. In this communication we review the
      literature reports of association of anti-phospholipid antibodies and
      infertility, and deal with the question whether they have a pathogenic role in
      these cases.

PMID- 9759132
TI  - Treatment of the antiphospholipid syndrome in pregnancy.

PMID- 9759133
TI  - Immunomodulation of experimental antiphospholipid syndrome.
AB  - The various therapeutic modalities which are found to be beneficial in
      experimental antiphospholipid syndrome include: bone marrow transplantation, anti
      CD4 monoclonal antibodies, bromocriptine, intravenous immunoglobulins and anti
      idiotypes, interleukin-3, and various anti-coagulant and anti-aggregate agents.
      The advantage of animal models is the ability to evaluate experimental treatments
      that cannot be tested directly on patients. In this paper, we review the effect
      of these agents on animal models of antiphospholipid syndrome, their mechanisms
      of action, and their clinical implications.

PMID- 9759134
TI  - Can we advise ovulation induction in patients with SLE?
AB  - The prognosis of systemic lupus erythematosus (SLE) has greatly improved during
      the last two decades, now allowing most patients to have a very long survival
      including a satisfactory quality of life. Initially considered contraindicated in
      SLE due to its overwhelming risks, pregnancy is nowadays allowed in a majority of
      patients, and fair results are usually obtained under appropriate management (1
      3). Consequently, patients thought to have infertility ask the question of a
      possible therapy, i.e. ovulation induction (OI) associated or not with in vitro
      fertilization (IVF). Considering the importance of estrogens in the pathogenesis
      of the disease, the use of such procedures raise several questions in SLE. Though
      data remain to date extremely scarce, the theoretical and practical aspects of OI
      in SLE will be briefly reviewed here.

PMID- 9759135
TI  - Do sex hormones modulate symptoms of inflammatory joint disease?

PMID- 9759136
TI  - Osteoporosis during pregnancy and its management.
AB  - Osteoporosis leading to fracture can occur during pregnancy. Bone density may be
      low before pregnancy due to recognised causes such as coeliac disease,
      osteogenesis imperfecta and previous anorexia nervosa (secondary osteoporosis).
      In some patients there is no identifiable cause. This condition is referred to as
      "pregnancy associated or pregnancy related osteoporosis"; it is not known whether
      pregnancy causes the osteoporosis or merely coincides with it. Typically the loss
      of bone leads to vertebral fracture with loss of height or pain in the hips also
      sometimes with fracture. Symptoms most often begin in the third trimester of the
      first pregnancy and improve after delivery; they do not usually recur in
      subsequent pregnancies. The cause is unknown and there is no specific treatment;
      follow up bone density measurements show that the osteoporosis slowly improves
      post partum. Recent research in non osteoporotic women shows that breast feeding
      maintains a low bone density; it is therefore contraindicated in pregnancy
      associated osteoporosis.

PMID- 9759137
TI  - Heparin-induced osteoporosis.

PMID- 9759138
TI  - Pregnancy in systemic sclerosis.

PMID- 9759139
TI  - Does SLE flare during pregnancy?

PMID- 9759140
TI  - Renal lupus in pregnancy.
AB  - The outlook of pregnancy for women with lupus nephritis is usually favourable if
      the disease has been quiescent for at least 3 months before pregnancy, and if, at
      conception, serum creatinine is less than 140 mumol/l, proteinuria less than 3
      grams/25 hours and blood pressure controlled. The risk of fetal loss is, however,
      2-3 times higher than in the normal population and pre-eclampsia, prematurity and
      fetal growth retardation frequently complicate these pregnancies. Pregnancies in
      women with lupus nephritis are high-risk pregnancies and they require intense
      fetal and maternal surveillance.

PMID- 9759141
TI  - Hypertension in pregnancy and preeclampsia--diagnosis and treatment.
AB  - Women who have or develop high blood pressure during pregnancy are all at
      increased risk of complications antenatally, intrapartum and in the puerperium.
      The increased risk applies to the mother as well to the fetus. Preeclampsia is
      the most serious form of hypertensive pregnancy complications. Preeclampsia is,
      however, not primarily a hypertensive disease but a disorder induced by factors
      dependent on the presence of placenta. The prime target of the placenta dependent
      factors is the vascular endothelium. Therefore the complications are associated
      with the vascular system, i.e. intravascular coagulation, bleeding and organ
      failure following poor perfusion. The fetus is at increased risk due to growth
      retardation and hypoxia following placental damage. Treatment of the hypertension
      is first indicated if the blood pressure rises to a level of increased risk of
      cerebral vascular complications, i.e. above 105-110 mmHg. Delivery is the only
      causal treatment and is always indicated if severe maternal or fetal
      complications develop.

PMID- 9759142
TI  - Prevention of thromboembolism in pregnancy.

PMID- 9759143
TI  - Utilization of intravenous immunoglobulin therapy to treat recurrent pregnancy
      loss in the antiphospholipid syndrome: a review.
AB  - Although experience is still limited, intravenous immunoglobulin therapy for
      recurrent pregnancy loss in the Antiphospholipid Syndrome (APS) may represent a
      significant advance. APS was widely recognized only fifteen years ago. Pregnancy
      loss and thrombosis are the prominent clinical features. Initially, prednisone
      was used for treatment of pregnancy loss, but matemal and fetal complications
      stimulated searches for alternative therapy. Subcutaneous heparin and low dose
      aspirin was next utilized, but although efficacious, there is still a 30% failure
      rate, and intrauterine growth retardation, prematurity, and pre-eclampsia are
      relatively frequent. In the late 1980's, there were a number of case reports of
      successful pregnancy outcomes after treatment with intravenous immunoglobulin
      (IVIg) but regimens differed. Series from two centers have confirmed these
      initial findings and treatment regimens have become more consistent. Both centers
      have reported success with doses of 400 mg/kg/day for 5 days or 1 g/kg/day for
      two days each month initiated during the first or early second trimester. Success
      rates of 70-100% have been reported, and complications such as pre-eclampsia,
      intrauterine growth retardation, and premature births appear reduced, when
      compared to prednisone and low dose aspirin or heparin and low dose aspirin.
      Several patients who were treated with IVIg also received heparin, making it
      uncertain whether heparin may also need to be added to IVIg. Intravenous
      immunoglobulin is safe, but expensive. Despite its expense, if IVIG is shown to
      markedly decrease matemal and fetal morbidity, it may be the logical treatment of
      choice to prevent pregnancy loss in APS.

PMID- 9759144
TI  - Intravenous gammaglobulin in pregnancy, the Connecticut experience.

PMID- 9759145
TI  - The Medical Birth Registry of Norway; a source for epidemiological and clinical
      research.

PMID- 9759146
TI  - Obstetrical and neonatal outcome in pregnant patients with rheumatic disease.
AB  - Possible associations between inflammatory rheumatic and connective tissue
      disease and adverse pregnancy outcome were assessed by using the Medical Birth
      Registry of Norway during the years 1967-95. All women with rheumatic disease
      were compared to women without such disease. Data on pregnancy outcome and
      deliveries were analyzed after adjustment for possible confounding factors. Women
      with rheumatic disease had significantly higher rates of preeclampsia, premature
      delivery and cesarean section as well a significantly increased relative risk of
      SGA children in all diagnostic groups in 1967-95. These findings emphasize the
      importance of close monitoring of pregnancy and delivery not only in patients
      with connective tissue disease, but also in patients with other inflammatory
      rheumatic disease.

PMID- 9759147
TI  - Reproductive events and the risk of development of rheumatoid arthritis.

PMID- 9759148
TI  - The effect of pregnancy on the vasculitides.
AB  - Vasculitis is a clinicopathologic process characterized by inflammation and
      necrosis of blood vessels. Classification schemes for systemic vasculitis depend
      on the size of the involved blood vessels, the anatomic site, and the clinical
      manifestations. The most common primary types of vasculitis are Wegeners
      granulomatosus, polyarteritis nodosa, and Churg-Strauss vasculitis. There is
      limited information on pregnancy outcome and medication use in these patients
      because most of the primary vasculidities occur in older individuals and they are
      more common in men.

PMID- 9759149
TI  - The teratogenicity of antirheumatic drugs--what is the evidence?
AB  - This review addresses on various methods used in the detection of human
      teratogenic effects of drug use in early pregnancy. Data are presented from the
      new Swedish ongoing recording of drug use in early pregnancy. These data do not
      indicate a teratogenic effect of the main antirheumatic drugs used in Sweden.

PMID- 9759151
TI  - Nonsteroidal anti-inflammatory drugs during pregnancy.
AB  - As inhibitors of cyclooxygenase nonsteroidal anti-inflammatory drugs (NSAID)
      given during pregnancy have the potential to cause adverse maternal and fetal
      effects. Maternal effects include prolongation of pregnancy and labour, whereas
      constriction of the ductus arteriosus, renal dysfunction and hemostatic
      abnormalities can occur in the fetus and neonate. Teratogenicity has not been
      found for the NSAID surveyed in this review. NSAIDs are excreted in small amounts
      into breastmilk with little risk for adverse effects in the suckling infant.

PMID- 9759150
TI  - Antimalarial drugs in pregnancy.

PMID- 9759152
TI  - The risk of cytotoxic drugs during pregnancy.

PMID- 9759153
TI  - Corticosteroids during pregnancy.
AB  - In pregnancy, pharmacokinetics of corticosteroids changes. Systemic
      corticosteroids are not teratogenic. Pregnant women receiving corticosteroid
      therapy suffer the same side effects and benefits as do treated women who are not
      pregnant. Clinical experience suggests no abnormalities of children of mothers
      treated with usual doses of prednisone and methylprednisolone throughout
      pregnancy, but premature rupture of amniotic membranes and low birthweight babies
      may occur. Betamethasone and dexamethasone are used to treat the fetus. The
      effect on the fetus of bolus doses of methylprednisolone is unknown. Very little
      corticosteroid ingested by the mother enters her breast milk. Corticosteroid
      therapy in pregnancy is appropriate to control clinically active maternal
      illness; to treat an in utero infant suffering from neonatal lupus-associated
      carditis; in stress doses (in corticosteroid-treated patients) for labor and
      delivery: and, pre-delivery, to induce fetal lung maturation.

PMID- 9759154
TI  - [2 significant stages in the management of mucoviscidosis: the French experience
      with dornase alfa (Pulmozyme) and the impact in international registries].

PMID- 9759155
TI  - [Respiratory evolution of patient with mucoviscidosis treated with mucolytic
      agents plus dornase alfa].
AB  - AIM: Modifications of bronchial secretions in cystic fibrosis patients account
      for the long-lasting use of mucolytic agents, despite the lack of adequately
      controlled clinical studies supporting this approach. Hyperviscosity of bronchial
      secretions mainly depend on their high DNA content, as a result of degradation of
      polymorphonuclear neutrophils mobilized by infection and inflammation. This
      phenomenon has led to the treatment of respiratory complications with human
      recombinant deoxyribonuclease (dornase alfa). In the present study, we compared
      the clinical and respiratory outcome in patients receiving mucolytic agents
      followed by dornase alfa, each for 1 year. POPULATION AND METHODS: Fifty-four
      patients, aged 5 years or more, have been prospectively followed for 2 years.
      They received first a 12-month association of mesna (two nebulisations per day)
      and oral ambroxol (60 mg per day, divided in two doses), followed by a 12-month
      treatment with one daily aerosol of dornase alfa only (2.5 mg per day). The
      primary end-points were the results of pulmonary function tests. Secondary end
      points were subjective symptoms, bacterial colonization, consumption of
      antibiotics, and clinical tolerance. RESULTS: At the end of the 12-month
      mucolytic therapy, a significant decrease of forced expiratory volume/second
      (FEV1, -10.5% as compared to baseline values) and forced vital capacity (FVC, 
      12.8%) was observed. At the end of 12-month dornase alfa, FEV1 and FVC had
      increased by 7.7 and 5.3%, respectively. This change was statistically
      significant only for FEV1 in most severely disabled patients. However, forced
      expiratory flow 25-75% (FEF 25-75) decreased during the 2 year period of
      observation, by 5.6% the first year and 4.9% the second year. The mean number of
      days with parenteral antibiotics did not statistically differ between both
      treatments, except for patients more than 15 years of age. In this subgroup, the
      mean number decreased from 40 days in the first year to 27 in the second year (P
      < 0.05). Acceptability of treatment by the patients themselves was better with
      dornase alfa than with mucolytic therapy. However, several episodes of
      hemoptysis, frequent in only one case, were associated with the treatment by
      dornase alfa. CONCLUSION: Dornase alfa was associated with a stabilisation, and
      even a trend to improvement in pulmonary function tests. This stabilisation is by
      itself a very encouraging result. Long-term comparative studies are needed to
      evaluate the benefits of dornase alfa in the treatment of respiratory
      complications of cystic fibrosis and specify the optimal modalities of its use.
      Synergistic combinations with mucolytic therapy and/or anti-inflammatory drugs
      could be viewed as a future prospect.

PMID- 9759156
TI  - [Effect of rhDNase on the respiratory function and nutritional status of children
      and adolescents with mucoviscidosis].
AB  - BACKGROUND: In 1994 we started recombinant human deoxyribonuclease (rhDNase) in
      every cystic fibrosis (CF) patient whatever his (her) clinical condition,
      provided they were aged more than 5 years and forced vital capacity (FVC) was >
      or = 40%. POPULATION AND METHODS: We reviewed retrospectively the effects of
      rhDNase in 69 CF children and adolescents during a 2-year follow-up. Patients (35
      boys, 34 girls) received 2.5 mg of rhDNase once daily from a mean age of 8.5
      years (range 5-16.4). Baseline spirometric values (% predicted) and nutritional
      status were as followed: FVC = 84.8 +/- 21.7; forced expiratory volume in 1
      second (FEV1) = 80.8 +/- 22.2; peak flow = 89.7 +/- 34.2, forced expiratory
      fraction 25-75% (FEF 25-75) = 71.8 +/- 32.8; Z score weight/height = -0.41 +/-
      1.14; Z score weight/age = -0.48 +/- 1.25, body mass index = 15.4 +/- 1.8;
      caloric intake = 107 +/- 25% of recommended dietary allowances (RDA). Patients
      had a Shwachman-Kulczycki's score of 87 +/- 9. Spirometric and nutritional data
      were analysed after 1, 3, 6, 12, 18 and 24 months of treatment and compared to
      baseline values (changes evaluated as percent change from mean baseline for
      spirometric data). Shwachman-Kulczycki's score was calculated after 24 months of
      rhDNase. RESULTS: An improvement of FVC (+10.7%, P < 0.001) and FEV1 (+12%, P <
      0.01) was noted after one month of treatment and was maintained throughout the
      following 2 years around 8.7% (6.4-11.4) for FVC and 8.2% (7.3-9.1) for FEV1, P <
      or = 0.01. This was particularly observed in children aged 5 to 10 years, in boys
      and in patients with a baseline FVC under 70% predicted. There was no significant
      change in FEF 25-75. We observed an improvement of daily caloric intake from the
      third month (P < 0.05) and of body mass index from the sixth month (P = 0.02).
      This was particularly noted in girls. Z score weight/age was improved only during
      the first 3 months of treatment while Z score weight/height increased only after
      a 2 year follow-up. There was no significant change in Shwachman-Kulczycki's
      score after 24 months of rhDNase. CONCLUSION: rhDNase in CF children in effective
      on lung function as well as on nutritional status and the response to this
      treatment can be evaluated after the first 3 months.

PMID- 9759157
TI  - [International registry on mucoviscidosis: comparison of the French data with the
      European data for 1995].
AB  - BACKGROUND: The Epidemiologic Registry of Cystic Fibrosis (ERCF) is an
      international registry, sponsored by Roche Laboratories, collecting data about CF
      patients in Europe. The aim of the our study is to compare the French data with
      the European data collected during the year 1995. RESULTS: By December 31st 1995,
      8,831 patients have been enrolled in Europe, including 1,457 patients in France.
      French CF patients are younger (mean age = 12.6 years) than European CF patients
      (mean age = 14.6 years). Genotype is better characterised in France (89 vs 75%
      for European patients), but only 49% of CF patients are homozygote for the DF508
      deletion in France versus 77% in Denmark. Two clinical features of French CF
      patients are interesting: 1) presence of Staphylococcus aureus and Haemophilus
      influenzae (52%) is more frequent in France than in Europe (65 vs 48% and 52 vs
      29%, respectively), 2) lung function tests (forced vital capacity [FVC]), forced
      expiratory volume per second [FEV1] are worse in France (P < 0.001) particularly
      in the older patients (> 18 years): 39% of these patients in France have a FEV1 <
      40% of predicted value compared to only 29% in Europe. Similarly there are fewer
      patients in this age group in France (22 vs 31% in Europe) having a FVC > 90% of
      the predicted value in France. With regard to the treatment, three differences
      emerge: 1) dornase alfa is more used in France (55 vs only 34% in Europe); 2) use
      of prophylactic inhaled and oral antibiotics is less common in France than in all
      age groups; 3) the use of inhaled corticosteroids and bronchodilators is also
      less common in France despite the same incidence of asthma-like symptoms. Finally
      we notice that the mean age at death in 1995 is 18.2 years (+/- 2.38) in France
      and 20.6 years (+/- 0.85) in Europe. CONCLUSION: These results are preliminary
      because 1995 is the first year for ERCF in France and a low percentage of French
      CF patients are included for this year. Therefore they must be interpreted with
      caution. Nevertheless, we can hypothesise about a relationship between these
      results and a less aggressive treatment regimen. The impact of dornase alfa use
      on prognosis seems interesting to analyse in future years.

PMID- 9759159
TI  - [Early myoclonic epileptic encephalopathy and non-ketotic hyperglycemia in the
      same family].
AB  - BACKGROUND: Neonatal myoclonic encephalopathy is of lesional or metabolic origin;
      non ketotic hyperglycinemia is one of its causes. CASE REPORT: A girl, born from
      consanguineous parents, died from myoclonic epileptic encephalopathy at the age
      of 3 months. Screening for metabolic disease was negative, except for increased
      levels of urine serotonin and 5-hydroxyindol-acetic in cerebrospinal fluid, blood
      and urine. Two sisters died with non ketotic hyperglycinemia, corpus callosum
      agenesis and clubfoot. CONCLUSION: Familial occurrence of non ketotic
      hyperglycinemia and early myoclonic epileptic encephalopathy is uncommon.

PMID- 9759158
TI  - [Exhale nitric oxide (NO) and respiratory function measured with body
      plethysmography in children].
AB  - BACKGROUND: Exhaled nitric oxide (NO) may be a marker of airway inflammation.
      Previous studies in adults have shown that the level of NO in exhaled air is
      influenced by several factors (breath holding, exercise, etc), or by several
      disease (asthma, congestive heart failure, diseases of the upper respiratory
      tract, cystic fibrosis, etc). However, few studies have been performed in
      children less than 3 years of age. The aim of this study was to determine
      endogenous NO levels in children with various diseases during lung volume
      measurements. PATIENTS AND METHODS: Fifty-two children aged 18.3 +/- 9.5 months
      were studied. The population was divided in two groups, according to the
      underlying disease: a group of 39 children with cystic fibrosis (n = 7),
      bronchopulmonary dysplasia (n = 17), asthma (n = 7) or recurrent respiratory
      tract infections (n = 8) and a second group of 13 children without respiratory
      disease. Lung function was measured by whole body plethysmography and several
      respiratory parameters were calculated (functional residual capacity [FRC],
      compliance and resistances of the respiratory system, trapped volume). NO
      production was measured on a chemiluminescence analyzer from mixed exhaled air
      collected into a bag, over a period of 5 minutes. RESULTS: NO production was
      related to disease: exhaled NO levels were three times higher in bronchopulmonary
      dysplasia and cystic fibrosis, compared to NO levels in children without
      respiratory disease. They were higher in asthma. They were not altered in
      recurrent respiratory tract infections. No correlation was found between
      respiratory parameters and NO production. However, exhaled NO levels were
      correlated to trapped volume, which defined dynamic part of pulmonary
      hyperinflation. CONCLUSION: Levels of endogenous NO in infants were similar to
      those measured in adults with and without inflammatory respiratory disease. Lung
      distention influenced exhaled NO production.

PMID- 9759160
TI  - [Iterative intestinal intussusception and appendiceal mucocele in an infant with
      mucoviscidosis].
AB  - Cystic fibrosis is a common and potentially life-threatening hereditary disease
      which can affect numerous organs, particularly the digestive tract. CASE REPORT:
      A 4.5-year-old boy exhibited two little known clinical manifestations: an
      appendiceal mucocele and repeated intussusceptions. In spite of an appendectomy,
      intussusception relapsed and an ileocolic resection was necessary 2 years later.
      DISCUSSION: Appendiceal diseases in cystic fibrosis represent a large spectrum,
      ie, distention on the appendiceal lumen, engorged with sticky mucous matter,
      which becomes an appendiceal mucocele, peritonitis with an appendiceal
      perforation due to delayed diagnosis since acute appendicitis is difficult to
      diagnose in these patients. Intussusception is rarely observed in cystic
      fibrosis. CONCLUSION: Appendiceal mucocele could be a cause of intussusception.
      If an appendectomy is performed, resection of a part of the cecum, around the
      appendix, could be useful in preventing again mucocele formation.

PMID- 9759161
TI  - [Localized neonatal convulsions and cerebral arterial infarction].
AB  - BACKGROUND: Stroke is a rare cause of neonatal seizures. CASE REPORTS: During a 5
      year period, eight full-term infants were admitted to hospital for seizures due
      to a stroke. Seizures began shortly after birth and were always one-sided. Early
      CT scans showed cerebral infarctions. Motor disabilities such as hemiparesis were
      found in three out of seven cases; language difficulties were observed in the
      same proportion; however all the children had not reached school age. CONCLUSION:
      Neonatal localized seizures may be symptomatic of a stroke and therefore justify
      a computerized tomography (CT) scan. Motor and cognitive sequelae require early
      management.

PMID- 9759162
TI  - [Left aortic arch--right descending aorta--right ductus arteriosus (encircling
      aortic arch). A rare malformation of the aortic arches].
AB  - Abnormalities of the aortic arch which are responsible for tracheobronchial
      compression are well known. This case demonstrates the value of magnetic
      resonance imaging (MRI) for diagnosis and suggests that recurrent respiratory
      symptoms should evoke these abnormalities in infancy. CASE REPORT: The authors
      report a very rare malformation of the aortic arch formed by encircling aortic
      arch, with left aortic arch, right descending aorta and right ligamentum
      arteriosum. It was revealed by airway disorders due to the compression of
      tracheobronchial axis by the ligamentum arteriosum. Section of the ligamentum
      permitted suppression of obstruction. The diagnosis of these abnormalities is
      usually established by means of oesophagogram, tracheobronchial endoscopy,
      angiography and MRI. CONCLUSION: In this case, MRI gave a better picture than
      angiography. Sections of the ligamentum arteriosum are sometimes ineffective when
      compression is due to the aorta itself. Aortic uncrossing, a more complex
      operation, is then necessary.

PMID- 9759163
TI  - [Use of the intraosseous route in a premature infant].
AB  - BACKGROUND: The intraosseous route (IOR) is a rehabilitated vascular access in
      emergency situations. Its indications and duration are defined, although the age
      limit at which it is usable is not clearly established. CASE REPORT: A 34-week
      old preterm neonate, without infection, receiving gastric gavage, developed, at 8
      days of life, a severe septic shock requiring ventilatory support and emergency
      volume expansion via a subclavian catheter. During the chest X-ray to check its
      position, the catheter was unfortunately pulled out. The child presented an acute
      desaturation with bradycardia, requiring bag ventilation and endotracheal
      epinephrine. The umbilical vein being unusable, an intraosseous access (20 G,
      distal hole, Cook) was performed at the upper tibial level to continue
      resuscitation and left in place for 14 hours to infuse antibiotics, inotropic
      support, blood products and colloids. Blood cultures grew Klebsiella pneumoniae.
      After a severe initial phase, course was favorable with normal examination at 3
      years without complication of the IOR. DISCUSSION: To our knowledge, it is the
      youngest child in whom IOR was performed. For neonates and especially preterms,
      the site of puncture is just below the tibial superior tuberosity, otherwise
      there is a risk of fracture of the diaphysis. This risk justifies the control of
      the IOR by X-ray. The place of the IOR among emergency vascular accesses in
      neonates, seems to us to be reserved to situations when umbilical vein is
      unusable. CONCLUSION: Although no study compared IOR to superior longitudinal
      sinus access, we suggest to reserve the sinus access only when IOR has failed,
      because of its potential cerebral complications.

PMID- 9759164
TI  - [Genetic basis of Prader-Willi and Angelman syndromes: implications for the
      biologic diagnosis].
AB  - Prader-Willi and Angelman syndromes are two genetic diseases whose clinical
      diagnosis is often impaired by a wide variability in some clinical findings. New
      insights in the genetic basis of these disorders allow the proposition of a
      biological approach to detect almost all Prader-Willi syndrome patients and over
      80% of Angelman syndrome patients. Moreover, the results of these tests are
      indispensable for the evaluation of the recurrence risk.

PMID- 9759165
TI  - [Legislative and ethical aspects of drug experimental in children and
      adolescents].
AB  - Experimentation of drugs in children meets with ethical and legal difficulties.
      After studying historical development of drug trials regulation, the different
      ways to define the modalities of clinical trials (law, technical aspect,
      deontology, ethics) are described. The importance of the informed consent and its
      particularities when children are concerned are emphasized. Finally, it appears
      ethical and necessary to practice drug trials in children in order to obtain safe
      and efficient drugs and prescriptions in pediatrics.

PMID- 9759166
TI  - [Intestinal malrotation complicated by intermittent and recurrent volvulus].

PMID- 9759167
TI  - [Follow-up of the premature infant: prevention of severe diseases and sudden
      death. Role of polysomnography].
AB  - Incidence and severity of apnea and bradycardia in preterm infants may be related
      to the immaturity of the respiratory control mechanisms. In addition, there is a
      steadily increasing risk for sudden death with decreasing birth weight or
      gestational age during the first year of age, justifying the search for a
      specific preventing strategy for very low birth weight (VLBW) infants. The
      purpose of this paper is to define practical preventive guidelines for VLBW
      infants at the time of discharge from the neonatal intensive care units.
      Polysomnography appears as a useful method to detect those among the VLBW infants
      who are at risk of life threatening events and may need home monitoring.

PMID- 9759168
TI  - [Home management of bronchopulmonary dysplasia].
AB  - Bronchopulmonary dysplasia remains a significant clinical problem associated with
      the success on survival of neonatal intensive care and has become the common est
      cause of respiratory insufficiency in infants. The severity of the disease is
      highly variable from asymptomatic chronic lung disease to patients needing home
      care with continuous oxygenotherapy and artificial ventilation. Management must
      try to insure not only appropriate growth and neurodevelopment but also
      satisfactory well being of the patients. Current medications (aerosoltherapy,
      diuretics, steroids), rules for oxygenotherapy, follow-up and expected evolution
      are discussed according to the severity of the disease.

PMID- 9759169
TI  - [Surveillance of the very-low birthweight infant: growth and nutrition].
AB  - In very low birth weight (VLBW) infants careful growth and nutritional
      supervision are necessary in order to reduce the incidence of persistent growth
      retardation after 2 to 3 years of age. Recently, post-discharge formulas with
      higher protein, energy and mineral content has been developed with the aim to
      promote catch up growth and mineral accretion during the first months of life.
      Based upon the most recent nutritional and growth data, the authors propose
      guidelines for the nutrition and growth follow-up of VLBW infants after discharge
      from the neonatal unit.

PMID- 9759170
TI  - [The premature infant confronting community-acquired infections. Which
      prophylaxis?].
AB  - Preterm infants are at high risk of severe community acquired infections. In
      particular viral respiratory infections, mainly respiratory syncitial virus
      infections (RVS), are responsible for a high incidence of rehospitalizations of
      preterm infants during their 2 first years of life. Prevention relies upon 1/the
      application of an immunization program identical to the program applied to normal
      term infants, a cardiorespiratory monitoring during 48-72 hours following
      immunization being recommended in those infants who carry a risk of recurrent
      apnea; 2/general measures with a demonstrated protective effect, i.e., breast
      feeding, elimination of smoking at home, and when possible limitation of contacts
      with infant and children communities. Immunoprophylaxis against RVS infections
      has been shown to be effective in reducing the severity of RVS infections in
      preterm infants but is presently not available in European countries.

PMID- 9759171
TI  - [Bacterial infections in the course of varicella: the role of NSAID?].

PMID- 9759172
TI  - [Drepanocytosis: is double-heterozygote S/C less severe than homozygote S/S?].

PMID- 9759173
TI  - [Type anti-SGPG antiglycolipid antibodies and Miller Fisher syndrome].

PMID- 9759174
TI  - [Allergy to hydrolysed cow milk proteins in premature twins].

PMID- 9759175
TI  - [Difficulty in measuring the viral load in the course of a HIV infection in the
      infant].

PMID- 9759176
TI  - [Schistosoma haematobium in an infant: a duodenal infection].

PMID- 9759177
TI  - [Arterial puncture in the premature newborn guided with a pulse oximeter probe].

PMID- 9759178
TI  - [Advances in the genetics of peripheral neuropathy in childhood].

PMID- 9759179
TI  - [Prematurity and neurologic sequelae: a hope for prevention?].

PMID- 9759180
TI  - [Retrospective survey of fluoroquinolone use in children].
AB  - BACKGROUND: Fluoroquinolones (FQ) are contraindicated in children because of the
      risk of cartilage damage. POPULATION AND METHODS: A retrospective survey
      concerning the use of FQ in children during the first 6 months of 1993 was
      organized in 1994. One hundred and sixty-seven Heads of pediatric departments
      were questioned. RESULTS: One hundred and fifty (90%) of those surveyed
      responded: 62 (41.3%) were FQ prescribers, 83 (55.3%) were non prescribers and
      five (3.4%) were not able to answer. Among the 62 prescribers of FQ, 17
      departments (27%) were not able to indicate the number of prescriptions and 45
      departments (73%) reported one to 75 prescriptions during the study period.
      Twenty-one departments out of the 45 were not able to identify the children
      treated with FQ. We obtained a group of 104 children aged 9.0 +/- 5.0 years (mean
      +/- standard deviation [SD]), treated with 165 courses of FQ during 20 +/- 45
      days (1-535 days) with concomitant treatments for 132/165 courses (80%). Fifty
      children (48%) were suffering from cystic fibrosis, 37 children (36%) were not,
      and, in 17, the diagnosis was not determined (16%). The FQ treatment administered
      either orally (73%) or intravenously (26%) was ciprofloxacin in 69% of the
      courses with a 25.1 +/- 7.0 mg/kg/day oral dose (mean +/- SD dose), and a 23.5 +/
      11.4 mg/kg/day intravenous dose, pefloxacin in 23 courses/165 (14%) with a 17.2
      +/- 3.8 mg/kg/day dose, ofloxacin in 15 courses/165 (9%) with a 21.0 +/- 11.9
      mg/kg/day dose, norfloxacin in 13 courses/165 (8%) with a 25.6 +/- 7.5 mg/kg/day
      dose. Twenty-one adverse events were reported in 17 children (16%) (11 of them
      with cystic fibrosis). These were cutaneous events (photosensitivity, cutaneous
      eruption) in eight courses, rheumatologic events (arthralgia, arthritis) in seven
      courses and gastrointestinal events (nausea, vomiting, diarrhea) in three
      courses. CONCLUSION: This survey shows that FQ are prescribed in children
      although their use is not approved in this age group and that numerous side
      effects have been recorded. The absence of exhaustive information (due to the
      retrospective nature of the survey) and the difficulties in interpreting the side
      effects for which validity and causal assessment have not been worked out
      according to a standardized method and in the absence of a control group stress
      the need for a prospective study.

PMID- 9759181
TI  - [Factors influencing the duration of breast feeding. A study of 150 women].
AB  - BACKGROUND: The duration of breast feeding has not yet been thoroughly described
      in France. A prospective survey has been performed on 150 breast feeding mothers
      to determine its duration. The objective of this study was to analyse predicting
      factors of this duration. METHODS: A questionnaire including sociological,
      psychological and medical variables was completed by the mothers and fathers.
      After discharge, the mothers were contacted every month by a physician until the
      completion of weaning. RESULTS: The median duration was 10 weeks. By univariate
      analysis, several variables were associated with a longer duration: decision to
      breast feed before pregnancy (12 weeks vs 9 weeks; P < 0.01), multiparity (17
      weeks vs 12 weeks, P < 0.05), high paternal social level (14 weeks vs 9 weeks, P
      < 0.001), high maternal education level (12 weeks vs 9 weeks; P < 0.05), mother's
      idea of "bad" milk (9 weeks vs 30 weeks; P < 10(-6), satisfied mothers (11 weeks
      vs 2 weeks; P < 0.001), motivation to breast feed (P < 0.05), baby and mother in
      the same room during the night (13 weeks vs 10 weeks; P < 0.05), and formula
      supplementation (6 weeks vs 13 weeks; P < 0.01). The mother's return to work was
      related to a decline in the breast feeding rate at 12 weeks, yet working women
      generally breast fed the most frequently before returning to work, and many women
      breast fed and worked concomitantly. A Cox multivariate analysis took into
      account six significant variables: "bad" milk (lower duration), mother who had
      been fed, mother satisfied with breast feeding, multiparity, high maternal
      education, closer proximity of baby to mother (longer duration). DISCUSSION: The
      duration in our study is longer than in other studies in France. Predictive
      factors are sociological, linked to maternal education, and psychological, with
      antecedent of mother breast feeding and decision before pregnancy. The role of
      the mother's occupation was not very important because working women are
      generally at a higher social level. The role of the father was analysed, as well
      as the role of professional workers, family and breast feeding women's
      associations. CONCLUSION: Factors of breast feeding duration can be somewhat
      modified, but it is necessary to respect the plans of both the mother and the
      father. However, early assistance in the hospital and after discharge can help
      parents realize their plans for prolonged breast feeding and helps obviating the
      cessation of 20% of mothers during the 1st month.

PMID- 9759182
TI  - [Neurogenic bladder in children with acute transverse myelopathy].
AB  - BACKGROUND: Neurogenic sphincter dysfunction may result from acute transverse
      myelopathy. The aim of this paper is to study the course of such a dysfunction
      and to propose management techniques. PATIENTS AND METHODS: The files of 21
      children admitted at the mean age of 8 years 5 months (2 to 14 years, 8 months)
      for acute transverse myelopathy were retrospectively studied. RESULTS: Bladder
      sphincter dysfunction occurred in the first days of disease in 85% of these
      patients. Abnormal perception of micturition was one of the most constant and
      specific symptoms. Anorectal function was also impaired. Complete regressive
      course was noted in 38% of patients, minor sequellae in 39% and major sequellae
      beyond 6 months of course in 23%. None upper tract deterioration was noted after
      3 years of course. Factors of favorable prognosis were early motor function
      recovery (especially recommencement of walking before 20 days) and early
      management of bladder dysfunction (inability to void had better prognosis than
      urinary incontinence). CONCLUSION: Early systematic bladder drainage in case of
      inability to void might be essential for improved prognosis.

PMID- 9759184
TI  - [Latrodectism in a child].
AB  - BACKGROUND: The malmignatte Latrodectus mactans tredecimguttatus, commonly known
      as a black widow spider, can be found in the Mediterranean region. Its bite is a
      cause of a rarely seen syndrome called latrodectism. CASE REPORT: During a visit
      to Corsica, a 13-year-old boy developed abrupt severe abdominal pain and
      spasmodic muscular contractions, headache and vomiting. The patient was restless
      and experienced hallucinations including distressing visions of death. His high
      blood pressure (154/100 mmHg) returned to normal within 3 days. Clinical
      examination revealed dyspnea and facial edema associated with
      blepharoconjunctivitis and hyperreflexia, together with a scattered erythema and
      pruritus. These changes took place within minutes, after a probable black widow
      spider bite. The abdominal and neuropsychiatric symptoms disappeared after 5
      days. Treatment with calcium gluconate, paracetamol, phloroglucinol and
      hydroxyzine had no effect, but diazepam decreased the acuteness of the symptoms.
      Anti-venom serum was not used. CONCLUSION: Diagnosis of latrodectism must be
      based on clinical and epidemiological data. Erroneously diagnosing surgical acute
      abdomen, renal colic, meningitis, tetanus or opioid withdrawal would entail
      incorrect treatment.

PMID- 9759183
TI  - [Exploration of 112 children suspected of amoxicillin allergy. Indications and
      efficacy of oral provocation test].
AB  - BACKGROUND: One to 10% of treatments using betalactams, particularly synthetic
      penicillin, are complicated by allergic reactions, usually cutaneous, and not
      easily imputable to immunologic sensitization in children. PATIENTS AND METHODS:
      The aim of this study was to identify, using cutaneous and biological tests,
      those from a group of 112 children suspected of amoxicillin allergy (evidenced by
      rash) who were actually sensitized, and to confirm the absence of allergy in
      others by an oral provocation test (OPT) associated to a long-term survey. The
      cutaneous tests were made by prick test and intra-dermo reaction (IDR) with
      Allergopen and with amoxicillin or amoxicillin + clavulanic acid. The biological
      tests included examination for penicillin and amoxicillin antibodies by using
      various techniques including enzyme-linked immunosorbent assay (ELISA)
      immunoglobulin G (IgG) and IgE, FARR, radioallergo sorbent test (RAST) and a
      histaminoliberation. When these tests were negative, an OPT with the suspected
      antibiotic was subsequently performed. RESULTS: Thirty-nine children (36.4%)
      confidently presented at least one positive cutaneous test (38 Allergopen, ten
      amoxicillin); 25 biological tests were positive (16 ELISA IgE, one ELISA IgG and
      eight histaminolibarations), seven times with negative cutaneous test. Forty-five
      children were judged to be sensitized to amoxicillin, with only one who
      subsequently took amoxicillin again. Among the 67 others, 52 received an OPT, six
      of them with moderate cutaneous reactions. Fifty-one (45.5%) children were
      allergic and 46 (41%) were allowed to take amoxicillin again; 17 did, one of them
      with a benign cutaneous reaction. CONCLUSION: Efficacy and safety of this type of
      investigation seems clear; it will have to be confirmed by other studies.

PMID- 9759185
TI  - [Focal dermal hypoplasia: description of three cases].
AB  - BACKGROUND: Focal dermal hypoplasia syndrome is mainly defined by the association
      of abnormalities of extremities, atrophy and linear hyperpigmentation of the
      skin, localized deposits of superficial fat, anomalies of the eyes and of the
      nails. Neonates are often small for their age. CASE REPORTS: Three sporadic cases
      are reported. Mental delay and omphalocele were observed in the first case. The
      neurological development was subnormal in the second and an unusual monodactyly
      was seen in the third. CONCLUSION: Most cases are sporadic, but in family cases,
      an X-linked dominant factor is likely. When a first affected offspring is
      observed, skin examination and X-ray should be carried out in parents to evaluate
      the risk of recurrence in their children. As the gene site has not yet been
      determined, antenatal diagnosis should be suspected on echography when fetal
      growth delay is associated to distal limb and/or ocular anomalies.

PMID- 9759187
TI  - [Vancomycin and cardiac arrest in the infant].
AB  - BACKGROUND: Different adverse effects induced by vancomycin bolus infusion are
      described, but cardiac arrest seems rare, in children as in adults. CASE REPORT:
      Two infants, 5 and 12 months old, were admitted after cardiac arrest, following
      vancomycin bolus infusion in excessive dose. They recovered after prompt
      resuscitation and their short term follow-up was normal. CONCLUSION: Two
      mechanisms are invoked: anaphylactic shock and direct cardiovascular toxicity.
      Both are dose- and infusion rate-dependent, and probably intersubject dependent.
      Usually, cardiac arrest is promptly reversed by adequate resuscitation. The rules
      of prescription are: adequate dilution and slow rate of infusion. If any adverse
      effect occurred, preventive antihistaminic drug therapy should be advised.

PMID- 9759186
TI  - [Urinary calculi and Munchausen syndrome].
AB  - BACKGROUND: Unlike the so-called Munchausen syndrome by proxy, which is a form of
      child abuse, Munchausen syndrome is seldom reported in pediatric literature. CASE
      REPORT: Anthony, an 8.5-year-old child, was referred because he passed several
      urinary stones. Although biological findings and urinary tract ultrasonography
      were normal, intravenous pyelogram showed a round area of decreased density in
      front of the anterior urethra, which disappeared from postmicturation X-ray. For
      a 1 month period, the child passed 20 stones without intense pain. After
      undergoing an appendectomy, he was readmitted for left lumbar pain which
      disappeared after passage of a stone. He spent the following 10 months without
      any complaint. On later re-admission with similar symptoms, Munchausen syndrome
      was suspected because of the discrepancy arising from the emission of stones on
      one hand and the absence of nephritic colic, of hematuria and of urinary tract
      dilatation on the other hand. Diagnosis of Munchausen syndrome was confirmed by
      chemical analysis which reported that samples were in fact ordinary pebbles and
      by child's confession, during interrogation without his parents, to having
      introduced the pebbles into his urinary tracts. CONCLUSION: When unusual clinical
      features are present in children, it is necessary to evoke the Munchausen
      syndrome which can be likened to a distress signal revealing the presence of
      psychological disorders.

PMID- 9759188
TI  - [Periventricular leukomalacia. I. Histological and pathophysiological aspects].
AB  - The term 'periventricular leukomalacia' (PVL) usually covers necrotic and/or
      gliotic lesions from perinatal origin occurring in the periventricular ring of
      telencephalic white matter. PVLs are found post-mortem in one third of brains
      from autopsies of premature infants; PVLs are diagnosed in 4 to 10% of infants
      born before 33 weeks of gestation and remaining alive more than 3 days after
      birth. PVL is very rare in at term infants. The proportion of PVLs from prenatal
      origin is estimated between one third and one half of cases. Recent progresses in
      neuroepidemiology, developmental neurobiology and imaging methods permit to
      revisit the pathophysiology of PVLs on a multifactorial basis. The final result
      of these multiple factors seem to be calcium influx due to glutamatergic
      overactivation triggered by cytokines, infection and inflammation, and deficit in
      neurotrophic factors. Periventricular topography can be explained by properties
      of intracerebral vascular wall at this stage of angiogenesis and by perfusion
      failure/hypoxia.

PMID- 9759189
TI  - [Periventricular leukomalacia and brain protection. II. Diagnosis, sequelae and
      neuroprotection].
AB  - The term 'periventricular leukomalacia' (PVL) usually covers necrotic and/or
      gliotic lesions from perinatal origin occurring in the periventricular ring of
      telencephalic white matter. Carrying motor and neuropsychological consequences,
      PVLs could be the most severe danger for very premature brains. Positive rolandic
      sharp waves recorded on EEG and precocious abnormally echogenous periventricular
      images on ultrasound suggest prospective periventricular cysts. Cystic
      periventricular cavitations certify the diagnosis of PVL. More subtle lesions of
      PVL do not reach the cystic grade and their diagnosis is confirmed by MRI.
      Treatment of infections is already available and potentially a tool for
      prevention. When the overwhelming glutamatergic signal has been triggered,
      neuroprotective agents turning off the excitotoxic cascade, including calcium
      blockers, growth factors and others, are promising therapeutic tools.

PMID- 9759190
TI  - [Treatment of apnea in prematurity].
AB  - Continuous monitoring of premature infants with apnea is mandatory in order to
      define the pathophysiology and the type of apnea, and to assess the efficacy and
      tolerance of the treatment. Etiological treatment must be first considered before
      deciding on a symptomatic treatment adapted to the type of apnea. In our
      practice, methylxanthines are the first line treatment considering their
      efficiency on the 'central' component of apnea of prematurity. In case of
      treatment failure, doxapram or continuous positive pressure can be associated to
      methylxanthines, especially when obstructive apnea or hypoventilation are
      predominant. The first attempt to stop the treatment is undertaken 4 to 5 days
      after complete resolution of apnea, starting with the last treatment used, the
      monitoring being maintained 4 to 5 days in order to detect eventual new apnea.

PMID- 9759191
TI  - [Radiological quiz of the month].

PMID- 9759192
TI  - [What uses for the acellular pertussis vaccine?].
AB  - The acellular pertussis vaccine offers a better tolerance as compared with the
      whole cell pertussis vaccine. It has also a good protective effect against
      whooping cough. However given as a combined pentavalent vaccine for the primary
      immunization of infants, it appears to introduce an immune interference leading
      to a diminished response to the Haemophilus type b or poliomyelitis valence
      according to the type of vaccine. Thus it is recommended that immunization
      against whooping cough in France in the coming years uses whole cell pertussis
      combined vaccine for the primary immunization of infants at 2, 3 and 4 months,
      the acellular pertussis vaccine being used for the booster injections at 18
      months and 10-11 years.

PMID- 9759193
TI  - [Rabies is a risk for travelling children].
AB  - Rabies remains a dreadful disease which kills about 50,000 people per year,
      mostly in Asia, Africa, South America and Central Europe. Between 30% an 50% of
      the victims are young children. Modern rabies vaccines are safe and immunogenic.
      Therefore parents must be informed on the risk of rabies, and pre-exposure
      vaccination must be performed for children traveling often or for periods longer
      than one month in canine enzootic countries. Post-exposure treatment must be
      initiated without delay with modern vaccines wherever available, according to
      approved schedules. Pre-exposure vaccination is particularly useful in remote
      places where modern vaccines and immunoglobulins are not readily available.

PMID- 9759194
TI  - [Assessment of developmental outcome of preterm babies].
AB  - Increasing survival of very preterm and sick neonates has lead to more concern
      about development outcome. Risk factors include antenatal, perinatal and
      socioeconomic factors. Developmental assessment has to be repeated during infancy
      till late school age (at term 3, 6, 12, 18, 42 months corrected age ...).
      Neurological examination, sensorial assessment and cognitive evaluation with
      special attention to visuo-spatial factors are mandatory.

PMID- 9759195
TI  - [Prematurity and infant-parent attachment disturbances. Assessment and
      intervention].
AB  - Premature birth is a factor of impaired infant-parent attachment. In addition it
      is frequently associated with other factors of impaired attachment related either
      to the infant (mainly the various pathologies of the premature infants and the
      hospitalization) and/or to the parents, specially the mother. The main
      characteristics of the normal process of infant-parent interaction are described
      as a basis for the early recognition and assessment of impaired interaction and
      preventive intervention.

PMID- 9759196
TI  - [Publishing in French].

PMID- 9759197
TI  - [Neuropathic pain associated with septic sacroiliitis].

PMID- 9759198
TI  - [Everything mothers want to know about the skin of their newborns].

PMID- 9759199
TI  - [Belief and practices of mothers in weaning infants between 0-24 months in
      Koumassi, Abidjan, Ivory Coast].

PMID- 9759200
TI  - [Treatment of asthma with drug inhalers].

PMID- 9759201
TI  - [Management of obesity in children and adolescents requires mobilization of all
      specialists].

PMID- 9759202
TI  - [Stopping measles with a second dose of vaccine].

PMID- 9759203
TI  - [Graft function following renal transplantation in children].
AB  - BACKGROUND: Since renal transplantation is known to be the best choice for the
      growing child with end-stage renal failure, we prospectively evaluated early and
      late graft function in transplanted children. POPULATION AND METHODS: The study
      included 78 children (32 girls, 46 boys) 10.4 +/- 0.6 years at the time of
      transplantation. Renal investigations were performed at 3, 6 and 12 months post
      transplantation and yearly thereafter. Inulin clearance was used to evaluate the
      glomerular filtration rate (GFR), and the reabsorption rates of Na, P and Ca were
      measured concomitantly. RESULTS: The overall adjusted GFR was approximately 70
      mL/min/1.73 m2 and remained unchanged during the first 5 years post
      transplantation. In the mean time the absolute GFR increased significantly,
      suggesting a remaining capacity for compensatory hypertrophy of the transplanted
      kidney. Renal function was significantly influenced by the number of rejection
      episodes during the first 2 years post-transplantation but no correlation was
      found between GFR and the number of HLA mismatches or the use of preemptive
      transplantation.

PMID- 9759204
TI  - [Long-term follow-up of children with esophageal caustic stenosis].
AB  - BACKGROUND: Long term follow-up of children with esophageal caustic stenosis is
      not well known. The aim of the present study was to describe functional, organic
      and psychological, as well as social consequences. PATIENTS AND METHODS: Thirty
      four children with a mean age of 3 years and 7 months +/- 3 years and 2 months
      (ranges: 1 month-14 years and 3 months) were included in a longitudinal study.
      Various parameters have been studied: treatment, functional symptoms, nutritional
      status (weight/height, body composition) and psychological and social
      consequences. chi 2 and Mann-Whitney tests were used for statistical analysis.
      RESULTS: Twenty-one patients have been treated by mechanical dilatations whereas
      surgery was performed in 12 children; the mean number of dilatations per child
      was higher in patients treated by dilatations (21 +/- 17 vs 14 +/- 16; P < 0.05).
      The frequency of dysphagia was not different in patients with colon interposition
      or not (69% vs 53%; P = 0.1). Nutritional status was not affected by the presence
      of esophageal caustic stenosis. Psychological and social consequences were
      characterized by scholastic difficulties, anxiety and severe depression. One case
      of suicide was observed. CONCLUSION: Children with caustic stenosis should be
      followed for a long period of time. A multidisciplinary approach is necessary,
      taking into account medical, social and psychological consequences.

PMID- 9759205
TI  - [Prevalence of Helicobacter pylori infection in children according to their age.
      A retrospective study].
AB  - The aim of this study was to evaluate the prevalence of H pylori infection in a
      Parisian children population. PATIENTS AND METHODS: During a 3-year period, H
      pylori infection was investigated in 623 children admitted to our hospital.
      Children were enrolled into two groups; either a symptomatic children group with
      clinical gastritis manifestations as infant colics or recurrent abdominal pain
      for more than 3 months in whom H pylori infection was suspected, or a control
      children group with growth retardation of more than -2 standard deviation (SD).
      Ethnic origin for all enrolled children was identified. A written parental
      consent was obtained for all children. H pylori infection was identified by
      enzyme-linked immunosorbent assay (ELISA) (Cobas Core Roche, IgG, 2nd generation,
      Roche, France). RESULTS: H pylori infection was identified in 99 children out of
      623 (15.8%). There was no difference between the two groups of children for age,
      sex, ethnic origin and prevalence of H pylori infection. The prevalence of H
      pylori infection was widely dependent on age and rose regularly with an annual
      acquisition rate of 2.1%. The prevalence of this infection varied from 1.8%
      during the first year of life to 30% in 15-year-old children. CONCLUSION: The
      latter prevalence is quite similar to that found in adults, suggesting that
      infection might occur in early life.

PMID- 9759206
TI  - [Breast feeding effect relative to age of onset of celiac disease].
AB  - BACKGROUND: Age at onset and clinical presentation of celiac disease have often
      been related to the age of gluten introduction into the diet. It has also been
      shown that breast feeding delays the onset of the disease. PATIENTS AND METHODS:
      This retrospective study attempts to evaluate the respective contributions of
      these two parameters in the determination of the age at onset of the symptoms in
      celiac Tunisian children. RESULTS: One-hundred-sixty-nine children were studied.
      Mean duration of breast feeding in our population was 9.6 +/- 8.9 months and mean
      age of gluten introduction was 5.6 +/- 3.2 months. The mean age at onset of the
      disease was 15 +/- 8.7 months and mean latency time between gluten introduction
      and onset of the disease was 9.5 +/- 7.8 months. Both variables, duration of
      breast feeding and age at gluten introduction were strongly correlated to the age
      at onset of the disease (r = 0.47 and 0.40, respectively). Only breast feeding
      was correlated to the variable latency time (r = 0.33). Stepwise multiple
      regression analysis showed that the two variables independently influenced the
      age at onset with coefficients of regression of 0.90 +/- 0.20 and 0.26 +/- 0.07,
      respectively. Only breast feeding influenced the latency time with a coefficient
      of regression equal to 0.26 +/- 0.07. DISCUSSION: Our study confirms the
      independent effect of breast feeding in the determination of the age at onset of
      the disease. Breast feeding has two effects: an indirect effect, by delaying the
      introduction of gluten, and a direct effect, by increasing the latency time
      between gluten introduction and onset of the disease. CONCLUSION: Prolonged
      breast feeding, at least until the 6th month, and gluten introduction started at
      least at the 5th month of life, significantly delay the onset of the disease.
      Gluten introduction should be done progressively and under breast feeding
      protection. Introduction of gluten 2 months before weaning has a protective
      effect.

PMID- 9759207
TI  - [Unusual presentation of nephroblastomatosis].
AB  - BACKGROUND: Nephrogenic rests generally constitute precursor lesions of Wilms'
      tumor. We report a case of right nephroblastomatosis with dysmorphic features.
      CASE REPORT: An enlargement of the right kidney was incidentally discovered in a
      1-year-old girl with dysmorphic features but normal psychomotor development.
      Combined ultrasonography and computerized tomography (CT) scan showed right
      cortical nephroblastomatosis. Chemotherapy using actinomycin D and vincristin was
      successful; however, an hyperechogenic nodule was subsequently found,
      necessitating a right nephrectomy. CONCLUSION: The relationship between
      nephroblastomatosis and Wilms' tumor is discussed. This case report reminds us of
      the importance of a long-term follow-up including echography and CT scan in cases
      of nephroblastomatosis.

PMID- 9759208
TI  - [Paraplegia due to medullary ischemia after repair of coarctation of the aorta in
      an infant].
AB  - Paraplegia after repair of coarctation of the aorta is uncommon. CASE REPORT: A 2
      month-old boy underwent excision of the coarctation area and primary anastomosis
      because of persistent heart failure. Spastic paraplegia was noted some hours
      after surgery. Motor deficit partially improved, but bladder dysfunction appeared
      some months after. Medullary magnetic resonance imaging (MRI) revealed an
      ischemia-related narrowing of the medullary diameter. CONCLUSION: Paraplegia
      after repair of coarctation of the aorta, described in adults and infants, is
      also seen in neonates. Prevention by preoperative monitoring of somatosensory
      evoked potentials is effective in adults, but difficult to perform in very young
      children.

PMID- 9759209
TI  - [Cystic papillary tumor of the pancreas: a rare etiology of abdominal mass in
      children].
AB  - BACKGROUND: Malignant pancreatic tumors are very uncommon in childhood. CASE
      REPORT: A 13-year-old girl was admitted for investigation of an abdominal mass
      with fever. Ten months earlier, clinical examination performed for similar
      symptoms found an epigastric mass which resolved spontaneously. Radiological
      investigations showed a well-encapsulated cystic tumor in the pancreas. Excision
      revealed a papillary cystic tumor of the pancreas. CONCLUSION: Papillary cystic
      tumor of the pancreas is an unfrequent cause of abdominal mass in children. Its
      excellent prognosis after complete excision is quite different from that of other
      malignant pancreatic tumors.

PMID- 9759211
TI  - [Intestinal flora in the neonate: impact on morbidity and therapeutic
      perspectives].
AB  - Studies in recent years have focused on the role that intestinal flora plays in
      health and disease. At birth, infant gut colonization begins with bacteria which
      are derived from the mother during delivery. Environmental factors (hospital,
      hygiene, antibiotics administered to the mother or to the neonate) may contribute
      to modification of the type of primary colonizing germs. Afterwards, diet
      represents the most important variable by the end of the first postnatal week.
      Exclusive breast-feeding promotes growth of Bifidobacteria which have been
      associated with the healthy nature of stool flora in infants because of their
      potential role in resisting pathogen colonization. Clinical trials have been made
      to promote bifidobacteria growth in the feces of bottle-fed infants. In addition,
      administration of non-pathogenic micro-organisms (probiotics) has been claimed to
      exert a positive influence on host health or physiology, and is a new approach to
      the prevention or elimination of infection originating from gut.

PMID- 9759210
TI  - [Bacteroides fragilis meningitis revealing a meningorectal fistula].
AB  - Cases of meningitis due to Bacteroides fragilis are rare; we report a case
      revealing a meningorectal fistula. CASE REPORT: A 2-month-old infant developed a
      severe sepsis syndrome following a rectosigmoidoscopy for rectal bleeding. Lumbar
      puncture diagnosed bacterial meningitis. Cerebrospinal fluid (CSF) culture
      evidenced B fragilis with betalactamase. The initial antibiotherapy was changed
      for imipenem-metronidazole, which is at present the recommended antibiotherapy.
      Malformation including pre-spinal tumor and meningorectal fistula was evoked on
      magnetic resonance imaging (MRI) and confirmed by surgery. The outcome was
      favorable after surgery and antibiotherapy. CONCLUSION: B fragilis meningitis are
      usually associated with sepsis, whose origin is obvious. In our case, meningitis
      was isolated, revealing a meningorectal fistula.

PMID- 9759212
TI  - [Vasoactive intestinal peptide: a novel neurotrophic factor].
AB  - Vasoactive intestinal peptide (VIP) is a 28-amino acid neuropeptide with potent
      growth-related actions on dissociated neural cells. In recent years its role in
      brain development has been elucidated: VIP has been shown to be a regulator of
      early neurodevelopment and embryonic growth, a stimulator of neocortical
      astrocytogenesis and a neuroprotective molecule against excitotoxic and other
      neurotoxic substances. Thus VIP appears as a fundamental regulator of brain
      growth and development, and a potent neuroprotective agent, possibly involved in
      pathological processes such as microcephalies and some neurological impairments
      observed in very premature babies. Similarly, VIP and VIP derivatives could
      represent a new avenue in the search of therapeutics for excitotoxic lesions of
      the developing brain.

PMID- 9759213
TI  - [Treatment of chemotherapy induced emesis in children].
AB  - In recent years, the management of chemotherapy-induced emesis in children has
      been greatly modified by the introduction of a new therapeutic class: serotonin
      antagonists. Based on a better knowledge of mechanisms, the treatment now uses
      combinations of different drugs. These treatments need to be carefully adapted to
      the patient and to the emetic risk of the chemotherapy, also taking into account
      the minimal cost. A gradual treatment proposal in five steps is described.

PMID- 9759214
TI  - [Radiological case of the month. Lipoma of the omentum].

PMID- 9759215
TI  - [Plea for an evaluation of beta hemolytic streptococcal tonsillitis: from
      diagnosis to treatment].
AB  - There is no justification to maintain a systematic antibiotic treatment of all
      tonsillitis as currently practiced in France. Indeed, it is today possible to
      exclude the streptococcal origin of tonsillitis with a fair probability using a
      rapid diagnosis test. It is therefore mandatory that these tests are made
      available to the French practitioner. Additionally, alternatives to the classical
      10-day penicillin V treatment of streptococcal tonsillitis must be seriously
      considered: shorter duration treatment with oral cephalosporins, macrolides or
      amoxicillin have proved to be as efficient and of lower cost; they are also
      probably safer due to a better compliance related to the shorter duration.

PMID- 9759217
TI  - [Diagnosis and treatment of rheumatic fever].
AB  - Rheumatic fever has become rare in France as in most developed countries.
      However, recent outbreaks have underlined the need for practitioners to remain
      vigilant and to maintain careful prevention. Polyarthritis and polyarthralgia are
      the main manifestations of rheumatic fever but they are not specific. Carditis is
      a major feature which affects only half the patients; cardiac ultrasonography is
      therefore very helpful with respect to positive and false positive diagnoses
      resulting from innocent murmurs. Fever, acute phase inflammatory markers, and
      evidence of streptococcal infection are of major importance and rheumatic fever
      must be disregarded in their absence. The treatment includes: 1) steroids for a 3
      month-period; 2) early antibiotic treatment of streptococcal carriage; 3) long
      term prophylaxis using intramuscular benzathine penicillin.

PMID- 9759216
TI  - [Acute tonsillitis: towards a new therapeutic strategy].
AB  - There is a need for revising the current practice for treatment of acute
      tonsillitis in France, i.e., systematic antibiotic treatment. There are three
      main reasons for this revision: 1) group A betahemolytic streptococcus is
      involved in only 20% of acute tonsillitis (80% being viral); 2) rheumatic fever
      has become very rare; 3) efficient rapid diagnostic tests are now available,
      allowing a selection of patients with streptococcal tonsillitis who must be
      treated.

PMID- 9759218
TI  - [The ophthalmological follow up of the premature infant must go on after the
      neonatal period].
AB  - Premature infants with very low birth weight (VLBW: < 1251 g) and/or gestational
      age lower than 32 weeks are at high risk of ocular abnormalities. Retinopathy is
      a well known complication of the neonatal period, but many abnormalities occur
      beyond the neonatal period, and must be carefully screened for years, mainly:
      cicatricial retinopathy, myopia, strabismus, glaucoma, retinal detachment and
      various functional visual impairments. Guidelines for the postneonatal screening
      of these abnormalities are given.

PMID- 9759219
TI  - [Hearing impairment in low birth weight infants: warning signs, diagnosis and
      rehabilitation program].
AB  - The incidence of deafness is high in children born prematurely as compared with
      the general population of children. Early start of the rehabilitation being an
      important prognosis factor the detection of deafness must be made as early as
      possible. Therefore a careful attention must be paid to any early signs of
      possible hearing imparment; parents concerns in particular must always be
      considered seriously. Diagnosis of deafness rests on behavioural tests and
      electrophysiological technics.

PMID- 9759220
TI  - [Cerebellum and brainstem ischemic infarction after dog bite to the neck].

PMID- 9759221
TI  - [Fetal alcohol syndrome and hypertrophic pyloric stenosis in two brothers].

PMID- 9759222
TI  - [Breast feeding: what role for the pediatrician].

PMID- 9759223
TI  - [Value of bone mineral content measurement in preterm infants given
      corticosteroids for bronchopulmonary dysplasia].

PMID- 9759224
TI  - [History of medical education in Amiens].

PMID- 9759225
TI  - [Congenital malformations in pediatric tumors].

PMID- 9759226
TI  - [Animal models of congenital malformations].

PMID- 9759227
TI  - [Dysmorphic syndromes and regulatory genes].

PMID- 9759228
TI  - [Pathogenesis: immunologic, infectious and genetic aspects].

PMID- 9759229
TI  - [Chronic inflammatory bowel diseases in the child: clinical aspects].

PMID- 9759230
TI  - [Treatment of chronic inflammatory bowel diseases in the child].

PMID- 9759231
TI  - [Current knowledge of simple transposition of great vessels].

PMID- 9759232
TI  - [Simple transposition of great vessels. Physiopathology, current management].

PMID- 9759233
TI  - [Transposition of great vessels: history of surgical repair].

PMID- 9759234
TI  - [Long-term outcome and prospects in managing transposition of great vessels].

PMID- 9759235
TI  - [Diagnostic assessment in neutropenia].

PMID- 9759237
TI  - [Diagnosis and evolution of autoimmune neutropenia in the child].

PMID- 9759236
TI  - [Neonatal neutropenia].

PMID- 9759238
TI  - [Functional respiratory examination in pediatrics: why and how?].

PMID- 9759239
TI  - [Functional respiratory testing in mucoviscidosis].

PMID- 9759241
TI  - [Respiratory function in respiratory distress syndrome].

PMID- 9759240
TI  - [Respiratory function tests in pediatric asthma].

PMID- 9759242
TI  - [Treatment of nephrosis in the child].

PMID- 9759243
TI  - [Primary IgA nephropathy in the child: natural history, epidemiology and
      prognostic factors].

PMID- 9759244
TI  - [Genetics and nephrotic syndrome].

PMID- 9759245
TI  - [Walking, detection of pathology].

PMID- 9759246
TI  - [Equine gait in the child (video recording)].

PMID- 9759247
TI  - [The limping child. Orthopedic approach and limits of pediatric orthopedics].

PMID- 9759248
TI  - [The child who falls].

PMID- 9759249
TI  - [Walking problems in neurology: kinesitherapy and what else?].

PMID- 9759250
TI  - [Introduction: basic aspects, problems and outcome in perinatal neurology].

PMID- 9759251
TI  - [Prenatal ultrasound diagnosis of anomalies and developmental disorders of the
      nervous system].

PMID- 9759253
TI  - [Treatment and decision tree in ante- and perinatal neurologic pathology].

PMID- 9759252
TI  - [Nuclear magnetic resonance brain imaging in the prenatal period].

PMID- 9759254
TI  - [Contributions and expectations of molecular genetics in perinatal neurologic
      diagnosis].

PMID- 9759255
TI  - [Vaccine trials in ambulatory pediatrics].

PMID- 9759256
TI  - [Vaccination strategies of tomorrow... is it necessary to revaccinate rubella,
      mumps and rubeola, and when?].

PMID- 9759258
TI  - [Treatment of bacterial diarrhea].

PMID- 9759257
TI  - [Nosocomial infections in pediatrics. Epidemiologic studies, importance of
      research networks. Members of REAPED research].

PMID- 9759260
TI  - [Epidemiology of neonatal primary bacterial infections].

PMID- 9759259
TI  - [Periodic fever in the child. Survey of Marshall syndrome. Pediatric Infectious
      Disease Pathology Group].

PMID- 9759261
TI  - [Using milk during acute diarrhea in the infant].

PMID- 9759262
TI  - [After milk: what, when, how, why?].

PMID- 9759263
TI  - [Malnutrition at the beginning of life: long-term effects].

PMID- 9759264
TI  - [Is it necessary to continue admitting children to the general hospital?].

PMID- 9759265
TI  - [Is it necessary to train generalists in urgent pediatric care? Experience with
      an inter-university curriculum of urgent care in pediatrics in the Rhone-Alps
      region].

PMID- 9759266
TI  - [Success and vicissitudes on organizing urgent care in pediatrics: presentation
      of a project of urgent pediatric medico-surgical care].

PMID- 9759267
TI  - [Imaging network and connection in pediatric care].

PMID- 9759269
TI  - [Gilbert's disease in 1998].

PMID- 9759268
TI  - [Noonan syndrome: an enigma].

PMID- 9759270
TI  - [Basedow disease in children: clinical and evolutive aspects].
AB  - PATIENTS AND METHODS: The initial symptomatology and long-term effects of
      antithyroid drug treatment are reported in children aged 11.7 +/- 3.2 years (52
      girls, 16 boys) with hyperthyroidism due to Graves' disease. RESULTS: A family
      history of thyroid pathology was found in half of the cases: 7% (five out of 68)
      of our patients have had another autoimmune disorder associated with
      hyperthyroidism. The most frequent and permanent clinical symptoms at diagnosis
      were goiter and tachycardia. Antithyroid drug treatment was always proposed at
      first line and resulted in a rapid decrease in clinical and biological signs of
      hyperthyroidism. Subtotal thyroidectomy (n = 19) was mostly performed because of
      non-compliance or recurrence of hyperthyroidism after medical treatment
      withdrawal. Significant adverse reaction (leukoneutropenia) was observed in only
      one patient. Survival remission times analysis (remission being defined as
      clinical and biological euthyroidism for more than 1 year after antithyroid drug
      withdrawal) realised in 50 subjects followed up for at least 2.5 years showed
      complete remission in 55% of the patients treated exclusively medically (n = 27),
      when lost to follow-up or surgically treated subjects were considered as
      incomplete observations. On the whole studied population (n = 50), the remission
      rate was of 30% (n = 15) with an average follow-up period after medical therapy
      withdrawal of 5.2 +/- 3.0 years (range: 1.4-12.3 years). At present, ten out of
      15 can be considered as healed (remission time for at least 2.5 years). Moreover,
      according to survival analysis, 75% of the remissions have a probability to occur
      in a delay of 4.6 +/- 1.0 years after the beginning of medical treatment.
      CONCLUSION: In this population, no remission after 7 years of antithyroid drug
      therapy was observed. Remission predictive factors remain to be defined.

PMID- 9759271
TI  - [Treatment of infantile spasms with vigabatrin as first-line therapy and in
      monotherapy: apropos of 70 infants].
AB  - BACKGROUND: Steroids (hydrocortisone or ACTH) still remain the usual treatment
      for infantile spasms (IS). However, since 1990, some authors have reported the
      efficacy of vigabatrin (VGB), especially in cases related to tuberous sclerosis.
      POPULATION AND METHODS: Seventy children with infantile spasms were treated by
      VGB first line monotherapy. Modalities of treatment and monitoring were the same
      for all children. VGB was given at the daily dose of 100 mg/kg during 1 week. If
      spasms persisted, the daily VGB dose was increased to 150 mg/kg during a 2nd
      week. In case of persistence of IS, on the 15th day, hydrocortisone was then
      added to VGB. Of the 70 infants, 39 were symptomatic and 31 cryptogenic. RESULTS:
      On VGB, 37 children (54%) stopped having IS within a mean 3.5 days. Response to
      VGB was different according to etiology. Among cryptogenic cases, 22 infants
      (71%) definitively stopped having spasms and only one relapsed. Among symptomatic
      cases, only 15 infants (38%) stopped having IS, and half (8/15) relapsed. VGB
      mean daily dose at cessation of spasms was 114 mg/kg. Side effects were transient
      drowsiness (27%) and agitation (12%). Mean follow-up was 10 months (1-24 months).
      Seventy-five percent of the infants presenting with a focus of spike after the
      1st month of treatment relapsed. CONCLUSION: Infants with cryptogenic spasms have
      a good response to VGB monotherapy. When mental retardation is noticed before IS,
      and MRI is normal, there is no efficacy. In these cases, the best treatment seems
      to be prolonged corticotherapy associated with VGB.

PMID- 9759272
TI  - [Definition and prevalence of school-age multi-handicaps].
AB  - BACKGROUND: Regulations concerning services for handicapped children in France
      have defined the notion of multi-handicap. There are, however, divergences in the
      procedures for applying this definition, and differences in the prevalence in
      different areas. This study is aimed at clarifying these two points. POPULATION
      AND METHODS: A survey in three French departments provided data about disabled
      children born between 1975 and 1985 who received services from the departmental
      committee for special education or from day hospitals. The data was
      systematically collected by a physician using medical files. RESULTS: The results
      showed that the group of multi-handicapped children was heterogeneous. The most
      restrictive definition (motor disability with profound mental retardation, bed
      ridden or restricted to a chair) resulted in a prevalence of 0.73%. A broader
      definition based on the concept of zero autonomy, but excluding mild or moderate
      mental retardation, resulted in a prevalence of 1.28%. CONCLUSION: The importance
      of specifying the objectives of a definition selected for operational reasons is
      stressed in order to improve the estimation of specific needs.

PMID- 9759273
TI  - [Comparison of the effect of subcutaneous injection of adrenaline and terbutaline
      in asthma crisis in infants].
AB  - BACKGROUND: Edema of the mucous membranes lining the airways is a major factor of
      airway obstruction in asthma. Stimulation of both alpha and beta-adrenergic
      receptors is thus logically useful to reduce edema through vasoconstriction and
      to cause smooth muscle relaxation. The aim of this work was to compare the
      effects of subcutaneous epinephrine vs terbutaline for treating acute attack of
      asthma in infants. PATIENTS AND METHODS: Fifty-four infants aged less than 30
      months admitted for acute asthma attacks were included in this study. None had
      previous cardiovascular or definite pulmonary disease and none had tachycardia
      above 200/min. The patients were randomly given subcutaneous epinephrine, 10
      micrograms/kg (n = 28) or subcutaneous terbutaline at the same dosage (n = 26).
      RESULTS: Improvement in accessory muscle use, oxygen saturation, PaO2 and PCO2
      was similar in both groups. The respiratory rate was significantly improved after
      administration of epinephrine (P = 0.05). No adverse effects were seen in either
      drug. CONCLUSION: Subcutaneous administration of epinephrine is as effective as
      terbutaline in treating acute attack of asthma in infants. This drug, easy to use
      and of low-cost, could be the treatment of choice in developing countries.

PMID- 9759274
TI  - [Familial Romano-Ward syndrome. Apropos of 2 new observations].
AB  - BACKGROUND: Congenital long QT syndrome is rare, usually revealed by bouts of
      syncopal attacks secondary to effort or strong emotions, and more rarely by
      atypical epileptic crisis. CASE REPORTS: We report a family history of two boys
      whose mother and grandmother both died suddenly a few days after delivery. The
      oldest child was 10 years old when admitted to hospital for recurrent loss of
      consciousness. Neurological examination and biological assays were normal;
      electrocardiography (ECG) revealed a prolonged QT interval of 0.59 seconds and
      episodes of torsades de pointe on the 24 hour ECG recording. The inefficacy of
      beta blocker treatment alone led to the implantation of a pacemaker; no
      recurrence has occurred since. The family investigation permitted to recognize
      the same syndrome in his asymptomatic 8-year-old brother for whom a prophylactic
      treatment was started. CONCLUSION: Both cases remind us of the necessity to carry
      out systematically an ECG in every child seen for unexplained malaise related or
      not to stress or for an atypical epileptic crisis. This is the only way for an
      early diagnosis on which the entire prognosis depends.

PMID- 9759275
TI  - [Severe streptococcal group A infection complicating varicella].
AB  - Varicella is a common viral infection which is generally benign in infancy and
      has a good outcome. It may sometimes be complicated by severe group A
      streptococcal superinfection. CASE REPORT: Three days after the beginning of
      varicella, a previously healthy 2-year-old girl presented with left leg pain,
      lameness and edema of all four limbs. Toxic shock syndrome occurred, due to beta
      hemolytic group A Streptococcus grown from blood culture. Computerized tomography
      (CT) scan showed a mild effusion involving both hips. Cefotaxim was administered,
      but the week after magnetic resonance imaging (MRI) showed a necrotizing
      fasciitis and a lesion of the left leg leading to a patchy femoral diaphysis
      consistent with osteomyelitis. Joint aspirate culture did not grow. The left leg
      was immobilized in plaster for 6 weeks and the child was given cefotaxim and
      fosfomycin parenterally during 30 days, then followed by 45 days of oral
      amoxicillin. She recovered without sequelae. CONCLUSION: Group A Streptococcus
      infection is a dangerous complication of varicella. It must be considered in case
      of any joint pain occurring during or just after this disease. The choice of the
      best treatment needs full collaboration between surgeons, radiologists and
      pediatricians.

PMID- 9759276
TI  - [Clear cell meningioma: recurrent intraspinal tumor in a child].
AB  - BACKGROUND: Meningiomas represent 1.5% to 4.3% of cerebral and medullar primary
      tumors in children. CASE REPORT: A 9-year-old girl had a history of thoracolumbar
      scoliosis. An intracanalar and extramedullar tumor was confined to the lumbar
      region. Resection identified a clear cell meningioma. A symptomatic and tumoral
      recurrence occurred 5 months later in the same region. After a second resection,
      the patient received radiotherapy. At 8 months follow-up, no recurrence was
      documented. CONCLUSIONS: A stiff and painful scoliosis can be predictive of
      expansive intracanalar tumor. The recurrent or multifocal evolution of clear cell
      meningioma show the "aggressive behavior" of this histological type. A preventive
      radiotherapy could be proposed, depending on the age of the patient and the
      localization of the tumor.

PMID- 9759277
TI  - [Protein and energy needs of the infant with severe malnutrition. Application in
      a hospital environment for the treatment of malnutrition caused by deficient
      intake].
AB  - Severe malnutrition is defined by a weight for height below 70% of international
      standards or by presence of oedema in a clinically undernourished child. Severe
      malnutrition associated with oedema is called kwashiorkor. The origin of oedemas
      of kwashiorkor is still debated, but its relation with protein deficiency is
      strongly questioned. The same dietary management is now recommended for
      malnutrition with or without oedema. Present recommendations are based, as for
      well nourished children, on the separate estimation of nutritional requirements
      for maintenance and growth. Total requirements vary between 0.7 g/kg/day in the
      first few days of treatment to 5 g/kg/day or more when weight gain is maximum. As
      a result of high energy requirement during catch-up growth, protein requirements
      never exceed 10 to 12% of total energy needs.

PMID- 9759278
TI  - [Intracranial hypertension in the infant: from its physiopathology to its
      therapeutic management].
AB  - The pathophysiology of elevated intracranial pressure (ICP) is assessed from a
      three cerebral compartment model and from brain compliance. The mechanisms
      leading to elevated ICP (expanding process, cerebral edema, brain swelling,
      hydrocephalus) and their consequences (brain herniation, ischemia-anoxia
      phenomenon, Cushing reaction and neurogenic pulmonary edema) are overviewed. The
      causes of elevated ICP in children are reported with emphasis on traumatology.
      Diagnostic procedures include clinical assessment, fundoscopy, cerebral
      computerized tomography scan and specific problems of cerebrospinal fluid
      investigation. Methods and results of intracranial pressure monitoring are
      reported. The treatment of elevated ICP is based upon clinical follow-up and
      monitoring of ICP. General therapeutic rules consist of adequate position,
      suppression of any neck, skull and abdominal compression, stimuli limitation and
      fluid restriction. Specific treatments include mechanical ventilation, sedation
      and analgesia, barbiturates, anticonvulsant drugs, mannitol, corticosteroids,
      hypothermia, enteral nutrition, and antibiotics.

PMID- 9759279
TI  - [Radiologic case of the month. Torsion of the transverse colon].

PMID- 9759280
TI  - [Prevention of infective endocarditis in the child. Current status and
      protocols].
AB  - Infective endocarditis remains a severe, potentially lethal disease, which
      justifies a rigorous prevention schedule. Children with cyanotic congenital heart
      disease, mitroaortic valvulopathies, prosthetic valve and uncorrected ventricular
      septal defect are the most susceptible. Dental care is the main cause of
      bacterial graft, followed by upper respiratory tract and cutaneous infections.
      Prevention is mainly based upon antibiotic prophylaxis but patient education and
      good dental hygiene are also important.

PMID- 9759281
TI  - [Why pediatric consultations increase in the centers for the socially excluded?].
AB  - Studies done by Medecins du Monde indicate that sanitary exclusion is a growing
      phenomenon in France, children included. Paediatricians must be concerned by this
      phenomenon, which is related to the social precarity of many families who do not
      use the standard health care structure. They must understand the reasoning behind
      the choices of these families, and be involved in the care of their children in
      places that they accept to visit. Paediatricians should also be present in
      institutions, conferences and debates where public health policy is discussed in
      order to defend the place of paediatrics in the sanitary organisation.

PMID- 9759282
TI  - [Hematuria in the child. Investigation plan in pediatric practice].
AB  - The discovery of hematuria in a child should lead the pediatrician to a
      methodical evaluation of the patient based on an extensive history and
      comprehensive physical examination. The microscopic examination of the urine is
      the cornerstone in the evaluation process and may suggest the origin of the
      hematuria. For instance, red blood cell casts indicate glomerular lesions and
      rule out the need for further urological examinations. According to the type of
      hematuria and the associated symptoms, a complete and immediate evaluation is
      sometimes necessary. This article presents a decisional tree to help the
      pediatrician to investigate an hematuria and to refer the child to a specialist,
      when needed.

PMID- 9759283
TI  - [Syncytial respiratory virus infections and ribavirin].

PMID- 9759284
TI  - [Clinical study of growth and puberty in girls in a school environment in Dakar.
      Survey on 722 cases].

PMID- 9759285
TI  - [Convulsive crisis and methemoglobinemia after the application of anesthetic
      cream].

PMID- 9759286
TI  - [Human science contribution in pediatrics].

PMID- 9759287
TI  - [Living donor kidney transplantation in the child].

PMID- 9759288
TI  - [An adolescent treatment unit: development and resistance].

PMID- 9759289
TI  - [Hypoplasia of the penis: etiologic diagnosis and results of treatment with
      delayed-action testosterone].
AB  - BACKGROUND: Results of long-term testosterone treatment of congenital hypoplasia
      of the penis are sparse; the aim of this work was to evaluate these results
      according to age at onset of treatment, the presence or absence of hypospadias,
      and its eventual adverse effect upon growth and bone maturation. PATIENTS AND
      METHODS: Sixty-six children with congenital hypoplasia of the penis, isolated (n
      = 31) or associated with a hypospadias (n = 35), were evaluated between 1 day and
      16 years of age. The prevalence (40% of the cases) of the different malformations
      and/or syndromes associated with congenital hypoplasia and its severity were not
      different whether the penis was isolated or associated with hypospadias (male
      pseudohermaphroditism). The effect of the testosterone heptylate (IM) was
      evaluated in 40 children treated before 10 years of age. RESULTS: The penis'
      increase in length was more important in the children with isolated micropenis
      (+2.1 +/- 0.8 SDS) than those with hypospadias (+1.3 +/- 1.2 SDS) but, in all
      cases, its increase was better when the treatment was started during the neonatal
      period, which corresponded to those with the most severe forms of micropenis. A
      mean regression of the penile volume of -0.7 +/- 0.8 SDS was noticed after the
      end of each stimulation. No long-term secondary effects related to treatment were
      seen on later growth and bone-maturation. CONCLUSION: Penile length at the last
      follow-up was not associated with total dose of testosterone but with its length
      at the first evaluation time (r = 0.52; P = 0.002).

PMID- 9759290
TI  - [Refractory pain in children with cancer: role of peridural analgesia].
AB  - BACKGROUND: Adequate treatment of pain in children with cancer is a critical
      issue, and is of equal importance as discussions concerning chemotherapy, surgery
      and radiotherapy. OBJECTIVE: To evaluate the treatment of refractory pain by
      peridural analgesia. METHODS: Seven children (1-15 years) with solid tumors were
      treated with long term epidural analgesia for refractory pain. Catheters were
      inserted in epidural space (L1-L2) and infused with sufentanil, bupivacaine and
      clonidine. RESULTS: Three out of five children with good response to peridural
      therapy could be discharged. A 12-month-old infant had a poor response. Treatment
      was discontinued in a teenager boy because of patient refusal. The side effects
      were: early catheter displacement in two patients and a bacterial contamination
      in one. Serious adverse effects related to high doses of opiates were not
      observed. However, toxicity of bupivacaine was observed in three patients leading
      to treatment discontinuation in one. CONCLUSION: Long-term epidural analgesia
      looks promising in selected children with refractory pain.

PMID- 9759291
TI  - [Mortality, morbidity and short-term neurologic outcome of premature infants less
      than or equal to 32 weeks gestational age in Fort-de-France CHR].
AB  - The mortality and neurodevelopmental outcome of premature infants born between 25
      and 33 weeks of gestational age in Fort-de-France (Martinique, French West
      Indies) is reported. POPULATION: The preterm cohort included 214 infants born
      during the years 1992 to 1995. RESULTS: The mortality rate during the
      hospitalization was 20%, but was only 14% when the birth weight was more than
      1,000 g. The main neonatal problems were: hyaline membrane disease (34%),
      bronchopulmonary dysplasia (6.5%), necrotizing enterocolitis (6%),
      intraventricular hemorrhage (9%) and periventricular leucomalacia (2%). Twenty
      infants (13.5%) showed abnormal neurodevelopmental outcome, with only three
      having major handicap. CONCLUSION: This study shows a notable improvement in the
      prognosis of premature infants in Fort-de-France. Nevertheless, a strong effort
      must be made in very low gestational ages and very low birth weight infants.

PMID- 9759292
TI  - [Adoption and chronic hepatitis B carrier state].
AB  - AIM: Because there are few adoptable children in France, parents, for the last 20
      years, have turned to international adoption. Alerted by the generally poor
      health of these children, we paid particular attention to their health problems
      and especially to infection by hepatitis B virus (HBV). POPULATION AND METHODS:
      The 60 internationally-adopted children seen from June 1993 to June 1997 were
      included in this study. All had hemogram and serum iron dosage, and search for
      intestinal parasites and tuberculosis was performed in each child, as were HBs
      antigen and HBs antibody screening. When HBs antigen was positive, HBe antigen
      and antibodies, HBV DNA and hepatitis C and delta serology were also studied.
      RESULTS: Six out of the 60 children were HBV chronic carriers. The six presented
      HBs antigen and five out of the six presented viral DNA. One child was co
      infected with delta virus. Serum aminotransferase was normal in three children
      and increased in the three others. DISCUSSION: Some internationally adopted
      children are exposed to chronic infection by HBV. This concerns children coming
      from countries known for the high frequency of the disease, but also children
      with long stay in Eastern European nurseries. Chronic HBV carriage puts the
      child, as well as the family and other children in institutions and/or schools at
      risk, thus necessitating preventive measures.

PMID- 9759294
TI  - [Facioscapulohumeral myopathy and germinal mosaicism].
AB  - BACKGROUND: Germline mosaicism is now well known to account for recurrence of
      hereditary human disorders. Facioscapulohumeral muscular dystrophy is an
      autosomal dominant disorder; its locus has been identified in the telomeric
      region of chromosome 4 at the q35 band. It appears to have a high rate of
      mutation. CASE REPORT: A young girl had presented from childhood signs of a
      severe form of facioscapulohumeral muscular dystrophy, but with no familial
      history. The diagnosis was ultimately confirmed at the age of 23 years by
      molecular studies evidencing the deletion. The same abnormality was sparsely
      found in the child's father who appeared to harbor the mutation as a germline
      mosaicism with no clinical expression. CONCLUSION: This case illustrates the
      possibility of severe facioscapulohumeral muscular dystrophy and the dominant
      transmission of the disorder which may be clinically occult. It underlines the
      importance of molecular biology and the difficulties of genetic counselling.

PMID- 9759293
TI  - [Trigonocephaly: isolated, associated and syndromic forms. Genetic study in a
      series of 278 patients].
AB  - From a series of 1,833 patients with craniosynostosis, 278 cases with metopic
      synostosis were analysed. The prevalence of metopic synostosis was estimated in
      the region of 1 in 15,000 children. PATIENTS AND METHODS: All patients with
      metopic suture fusion were selected, excluding cases where additional sutures
      were involved. The age at diagnosis was between 15 days and 15 years. The
      diagnosis was based on clinical and radiological evaluation. The search for
      associated malformations was based on clinical evaluation, CT or MRI scans, bone
      X-rays and ultrasounds. If possible, a study of the karyotype was performed in
      case of associated malformation. Family information was obtained through contact
      with the families, generally in person or sometimes by telephone. The series was
      divided into three groups: isolated trigonocephaly (group 1), trigonocephaly
      associated with other malformations without any known syndrome (group 2) and well
      delineated syndromes (group 3). RESULTS: There were 213 males and 65 females, a
      sex ratio of 3.3. Family information was obtained from 222 probands distributed
      among 216 families. There was no maternal or paternal age effect. The frequency
      of twinning was 7.9%, with three concordances for metopic synostosis in three
      monozygotic twin pairs. A positive family history was obtained in 13 of the 216
      pedigrees, giving a 6% figure of familial cases. A vertical transmission was
      observed in only one case; in all other cases, there were two affected children
      with normal parents. Eleven familial cases were isolated trigonocephalies, and
      two were syndromic. Nine of the 53 available karyotypes were abnormal, involving
      the chromosomes 7, 9, 11 or 13. There were 208 observations in the group 1. In 53
      cases (group 2), associated malformations involved mainly the heart (12 cases),
      the limbs (six cases), the brain (five cases) and the genito-urinary tract (four
      cases). These malformations were unique in 32 cases and multiple in 21 cases.
      Some: of the observations could represent new syndromes. Seventeen syndromes
      represented group 3. Nine were chromosomal syndromes. Eleven presented with
      multiple malformations. An in utero exposure to valproic acid was observed in two
      cases of the group 1, five cases of the group 2 and one case of the group 3.

PMID- 9759295
TI  - [Secondary kidney amyloidosis and mucoviscidosis].
AB  - BACKGROUND: Due to the improvement in cystic fibrosis management, life expectancy
      has risen; on the other hand, longer survival has led to new complications,
      including secondary renal amyloidosis, which has been so far very uncommonly
      reported. CASE REPORTS: Secondary nephropathic amyloidosis was seen in two 25
      year and 22-year-old adults with cystic fibrosis. Both had developed recurrent
      pulmonary infections due to Pseudomonas aeruginosa over several years. One
      patient died after 2 years of progressive kidney failure. CONCLUSION: Severe
      renal insufficiency due to secondary amyloidosis may complicate the course of
      cystic fibrosis and become the main prognosis factor in adults.

PMID- 9759296
TI  - [Acute rhabdomyolysis in the child].
AB  - Rhabdomyolysis results from muscular fibre lysis with release of cellular
      contents (myoglobin, enzymes, electrolytes) into the plasma. Traumatic (crush
      syndrome) and non-traumatic rhabdomyolysis have been mostly reported in adults.
      Traumatic rhabdomyolysis are mostly due to ischemic and reperfusion injuries. Non
      traumatic rhabdomyolysis include several factors: muscular compression (comas),
      cytotoxic injury (infections and poisonings), ischemia (shock, cardiorespiratory
      arrest) or excessive muscular activity (seizures, strenuous exercise). The main
      etiologies reported in children are: anoxic-ischemic encephalopathy (including
      sudden infant death and life threatening events); electrolyte disorders; severe
      hyperthermia; poisonings; hereditary myopathies. Non-traumatic rhabdomyolysis
      must be suspected in these circumstances, requiring blood creatinine
      phosphokinase measurements. Indeed, clinical signs are inconstant and non
      specific, and functional signs are difficult to appreciate in children. During
      the initial phase, the main risk is arrhythmias secondary to hyperkalemia. The
      two main complications are the compartmental syndrome leading to irreversible
      vasculo-nervous injuries and acute renal failure. Treatment of traumatic and non
      traumatic rhabdomyolysis includes correction of hyperkalemia, active fluid
      loading in order to prevent acute renal failure and alkalinisation. Prognosis of
      rhabdomyolysis relates to the aetiology and the presence of acute renal failure.

PMID- 9759297
TI  - [Oculocutaneous albinism: clinical, historical and anthropological aspects].
AB  - Albinism represents a group of inherited abnormalities of the melanin pigment
      system in which the synthesis of melanin is absent or reduced, generalized
      (oculocutaneous albinism) or localised (ocular albinism). Recent molecular
      studies provide insight into the pathophysiological processes of pigmentation
      regulation and help our understanding of the genetic heterogeneity of human
      albinism. It rarely affects Europeans, frequently Africans, only a minority of
      Amerindians, who nevertheless, when an ethnic group is concerned, presents one of
      the highest incidence in the world. Historically, the African albinos were used
      as an alibi by the European theologians to support Adam's descent of humanity and
      by naturalists to affirm the alleged superiority of the white men.
      Anthropological data are mainly issued from Amerindians with contradictories
      attitudes towards albinos: both acceptance and rejection. Only the Kuna of Panama
      have given albinos a major place in their mythology, although in reality they
      frequently reject them.

PMID- 9759298
TI  - [Lichenoid eruptions in the child].
AB  - Lichenoid eruptions are represented by lichen planus and lichen striatus. They
      are characterized clinically by a papulous eruption, and histogically by a dermal
      superficial infiltrate of lymphocytic cells and a cytotoxic reaction directed
      against basal keratinocytes. The main differential diagnosis is hamartoma, the
      differentiation being important because of the possible association of haemartoma
      with malformations.

PMID- 9759299
TI  - [Acute scrotum in the child].
AB  - Torsion of the spermatic cord is the most common etiology of acute scrotum in
      children. Children with torsion usually present with acute scrotal pain, nausea
      and vomiting, and only early surgical treatment, within 6 hours of the onset of
      symptoms, may ensure the preservation of the testis. For that reason any acute
      scrotal pain with edema requires urgent specialized evaluation. Other etiologies
      include less severe diseases as torsion of an appendage, epididimytis, trauma,
      and other rare conditions such as acute idiopathic scrotal edema.

PMID- 9759300
TI  - [Diagnosis and treatment of vasovagal syncope in the child and adolescent].
AB  - Recurrent unexplained syncope is a common and often frustrating clinical problem
      in paediatrics. Over the last decade, head upright tilt table testing has emerged
      as an important diagnostic method for the identification of patients whose
      syncope is likely to be neurocardiogenic in origin. At the same time, tilt table
      testing, by providing syncopal episodes in a controlled setting, has allowed for
      a greater understanding of their physiopathology. Treatment strategies remain
      controversial but beta-blocker therapy appears to be very efficient.

PMID- 9759301
TI  - [Association of Guillain-Barre syndrome and mumps in a 13-month-old infant].

PMID- 9759302
TI  - [Secondary fatal acute pancreatitis in ascaridiasis in a 4-year-old child].

PMID- 9759303
TI  - [Spondylocostal dysplasia in Jarcho-Levin syndrome].

PMID- 9759304
TI  - [Benign intracranial hypertension after treatment with pefloxacin].

PMID- 9759305
TI  - [Sudden death caused by abnormal origin of the left coronary artery from the
      sinus of Valsalva].

PMID- 9759306
TI  - [Calcium administration in the Brazzaville child].

PMID- 9759308
TI  - [Blood transfusion in very premature infants].

PMID- 9759307
TI  - [Unusual mechanism in Prader-Willi syndrome: incidence in genetic counseling].

PMID- 9759309
TI  - [Pediatric survey of perinatal care networks in France].

PMID- 9759311
TI  - [Urinary tract infection in ambulatory pediatrics].
AB  - A survey by questionnaire on urinary tract infection (UTI) in children was
      conducted over a 1-year period among paediatrician practitioners (April 1997
      March 1998). The aim was to provide epidemiological data and to describe the
      current therapeutic attitude on UTI in children in paediatrician practice. The
      preliminary results will be presented during the meeting on UTI in children.

PMID- 9759312
TI  - [Current definition of urinary tract infection in the child].
AB  - Urinary tract infections (UTI) encompass a spectrum of clinical and pathological
      conditions involving various parts of the urinary tract. Differentiating the
      syndromes associated with UTI has important implications for treatment and
      prognosis. To effectively communicate information on the subject, terminology
      should be standardized and precise--a challenge as it is difficult to strictly
      adapt the terms into French and subsequently apply them to practice.

PMID- 9759313
TI  - [Urinary tract infection in the newborn infant].
AB  - Urinary tract infection in the first month of life may be revealed by isolated
      fever, poor weight gain or severe sepsis. It is more frequent in male infants.
      Escherichia coli is the most common infecting agent. A urinary tract malformation
      is found in approximately 30% of the cases. In most cases intravenous treatment
      with an association of cephalosporin and aminoside is efficient. However, because
      of the possible involvement of an enterococcus, amoxicillin must be added until
      the result of the urine culture is available. Prophylaxis with oral
      administration of antibiotics is recommended in case of urinary tract
      malformation.

PMID- 9759314
TI  - [Microbiological diagnosis of urinary tract infections in the child. Importance
      of rapid tests].
AB  - Urine collection study is one of the most common means of bacteriological
      diagnosis in the laboratory. However, numerous interpretation problems exist. The
      aim of this paper is to specify these problems and to indicate the place of rapid
      tests in the screening for urinary tract infection. Direct examination must be
      performed on rapidly collected and transported urine. In such conditions, absence
      or presence of both leukocytes or germs presents a good negative or positive
      predictive value. However, false positive leukocyturia is frequent. False
      positive bacteriuria is mostly due to bad collection or transport. In some cases
      the threshold of bacteriuria > or = 10(5) cfu/mL can be reduced. Rapid tests
      include leukocyte esterase and nitrite tests. In our study, recording 289 tests,
      we observed negative and positive predictive values of respectively, 92% and 100%
      when the two tests were used together. Dipsticks can be used to exclude a urinary
      tract infection when clinical symptoms are absent, but only if they are used
      correctly. When both tests are positive, a urinary tract infection is likely.
      Study on urine collection is difficult in children. Collaboration between
      clinician and bacteriologist is essential.

PMID- 9759315
TI  - [Antibiotic sensitivity to isolated bacteria in pediatric urinary tract
      infections].
AB  - Of the childhood urinary tract infections, more than 50% are caused by
      Escherichia coli (E Coli), followed by Proteus mirabilis (P mirabilis),
      Klebsiella sp, other enterobacteria, enterococci, Pseudomonas aeruginosa, and
      staphylococci. Of E coli isolates, 50 to 60% are resistant to ampicillin (ampi
      R), 10% being susceptible to amoxicillin + clavulanic acid (AMC). For P
      mirabilis, ampi-R isolates are less frequent and more often susceptible to AMC.
      Klebsiella sp is resistant to ampicillin, 75% of isolates being susceptible to
      AMC. In these three species, the susceptibility of isolates to third generation
      cephalosporins, aminogly-cosides, and ciprofloxacin is still high (> 90%), but 15
      to 35% are resistant to cotrimoxazole. In the other enterobacteria (Enterobacter
      cloacae, Morganella morganii, P vulgaris, Citrobacter freundii and Serratia
      marcescens) the resistance to cefalotin (hence to ampicillin and AMC) is
      permanent, with an exception: the susceptibility of P vulgaris to AMC.
      Enterococci are mostly susceptible to ampicillin, and P aeruginosa to
      ceftazidime, but in both species, the percentage of resistant strains in
      hospitalised patients is greater than in outpatients. For Staphylococcus aureus,
      the community-acquired isolates are susceptible to oxacillin and other anti
      staphylococcal agents. All the coagulase negative staphylococci isolates are
      susceptible to vancomycin, but 70% of those from hospitalised patients are
      resistant to oxacillin, aminoglycosides and cotrimoxazole.

PMID- 9759316
TI  - [Urinary tract infection and biological markers: C-reactive protein, interleukins
      and procalcitonin].
AB  - Serum C reactive protein (CRP) remains a good marker of the severity of urinary
      tract infections in children, despite false negative results. Serum IL-6 is not a
      better marker; urinary IL-6 might have a better prognostic value as it is higher
      in patients with renal lesions due to infection, but low values are found in some
      cases. Serum procalcitonin levels are correlated with the importance of renal
      scars at scintigraphy, with less than 10% of false negative results. Further
      studies are needed to confirm the sensitivity and sensibility of these markers,
      especially for procalcitonin.

PMID- 9759317
TI  - [Nosocomial urinary tract infections: retrospective study in a pediatric
      hospital].
AB  - Urinary tract infections (UTI) are the most frequent nosocomial infection in the
      adult, yet very few data are available concerning these infections in children.
      In a retrospective 1-year study in a paediatric hospital, we analysed the
      incidence of nosocomial UTI and the characteristics of the affected children. The
      incidence was of 1.97/1,000 admissions which represented 6.8% of all UTI
      diagnosed by the microbiology laboratory. Most cases were in surgery and
      neurology wards. The frequency was inversely proportional to the age, with 50% of
      children being less than 2 years old. Pathogens most frequently isolated were E
      coli (39%), Pseudomonas sp (12.1%) and Enterococcus sp (12.1%). When compared
      with the organisms found in all the urine cultures during the same period, two
      organisms were more frequently found in nosocomial urinary tract infections:
      Pseudomonas sp and Candida sp. Most patients presented one or more risk factors,
      mainly:bladder catheterisation (41.4%), prior antibiotic therapy (62%), cerebral
      palsy (6.9%). No bacteriema was observed. The diagnosis of nosocomial UTI must be
      interpreted with caution and needs close collaboration between microbiologists
      and paediatricians. These infections increase the cost of hospitalisation, but
      only exceptionally do they present with complications. Some risk factors are
      inherent in hospital conditions, but others can be reduced by improving hand
      washing or by changing catheterisation practices.

PMID- 9759319
TI  - [Initial imaging in pediatric urinary tract infection].
AB  - First step imaging investigations in urinary tract infections in children rely
      upon conventional sonography, and, when available. Power Doppler sonography.
      Enhanced computerised tomography (CT) and dimercaptosuccinic acid (DMSA)
      scintigraphy are complementary investigations in difficult cases. Contrast
      cystourethrogram has always to be performed. Intravenous pyelography is no longer
      used as a first step imaging technique.

PMID- 9759318
TI  - [Escherichia coli virulence factors in pediatric urinary tract infections].
AB  - As many as 90% of all community-acquired urinary tract infections (UTIs) and more
      than 30% of nosocomially acquired UTIs are caused by E coli. The migration of
      bacteria into proximal urethra and bladder mucosa requires that the organisms
      travel "upstream" and resist being carried away by the flow of urine.
      Colonisation requires binding of specific adhesions of the bacteria to
      appropriate receptors on the surfaces of the epithelial cells. P fimbrae are
      found in 80%, 30% and 20% of strains from patients with pyelonephritis, cystitis
      and asymptomatic bacteriura, respectively. P fimbrae are found in only 30% of
      strains isolated from patients with pyelonephritis associated with compromising
      host factors such as vesicoureteral reflux, urinary tract anatomical
      abnormalities and recent urinary tract instrumentation.

PMID- 9759320
TI  - [Role of DMSA scintigraphy in managing pediatric pyelonephritis].
AB  - Pyelonephritis in children may lead to irreversible renal damage and eventually
      to arterial hypertension and renal insufficiency. Inflammation plays a central
      role in the pathogenesis of pyelonephritis. Dimercaptosuccinic acid (DMSA)
      scintigraphy permits detection of acute renal lesions and renal scars with high
      sensitivity and specificity. In our experience 60% of patients who had acute
      renal lesions on DMSA scintigraphy during pyelonephritis develop scars. Young age
      appears to be not a risk factor, as in our experience 70% of children older than
      5 years develop scars compared to 40% for children younger than 1 year. In
      addition, only 40% of patients who develop scars have vesicoureteral reflux. DMSA
      scintigraphy may provide answers to important clinical questions: what is the
      optimal length of treatment of pyelonephritis? Is parenteral treatment necessary?
      What is the best treatment of vesicoureteral reflux? DMSA scintigraphy permits
      therapeutical decision-making according to the renal involvement in each of our
      patients.

PMID- 9759321
TI  - [Parenchymatous cicatrix and urinary tract infection: physiopathology and
      clinical implications].
AB  - Renal scarring is the main long term complication of acute pyelonephritis in
      children. The prevalence rate is hazardous since data from the literature are
      confusing with respect to reflux nephropathy, chronic pyelonephritis and renal
      hypoplasia. The pathology of such lesions consists in focal interstitial
      fibrosis. When the first pyelonephritic attack occurs during infancy, renal
      growth may be compromised. The current approach of renal scar assessment is based
      on dimercaptosuccinic acid (DMSA) scan. Bilateral extensive lesions may be
      responsible for altered glomerular filtration rate (GFR) and/or arterial
      hypertension. The management of overt scarring is conservative and careful
      prevention must be based on early and aggressive treatment of acute
      pyelonephritis.

PMID- 9759323
TI  - [Curative treatment of lower urinary tract infections].
AB  - Because it is limited to the bladder, infection of the lower urinary tract does
      not lead to renal scaring. It may be symptomatic or asymptomatic. When
      symptomatic it never includes high fever and general symptoms. Only symptomatic
      infections need treatment using oral antimicrobial monotherapy for 5 to 7 days.
      It is necessary to search for a predisposing factor--mainly bladder dysfunction
      and constipation.

PMID- 9759322
TI  - [Antibiotic treatment of acute pyelonephritis in the child].
AB  - Antimicrobial therapy for pyelonephritis in children must quickly eradicate the
      bacterial infection and prevent scars in renal parenchyma. Escherichia coli (E
      Coli) is found in about 90% of cases of acute pyelonephritis in outpatients, 40%
      of E coli being ampicillin-resistant. The present effective antibiotics are: 3rd
      generation cephalosporines, amoxicillin-clavulanic acid association, and
      aminoglycosides. In the literature therapeutical guides are divergent concerning
      the route of administration (oral or i.v.), mono or bitherapy, the duration of
      the treatment (usually for 10 days), and the need for hospitalisation. The
      criteria for choice are risk factors such as: very young age (< 6 months), fever
      with toxic symptoms, vomiting, dehydration, uropathy, and poor compliance. There
      are few long term studies which compare two, therapeutic regimens and no
      evaluation of the frequency of consequent chronic pyelonephritis in adult age has
      taken place. Recent data suggest that an oral sequential treatment may permit a
      shorter hospital stage. The trend is chiefly to do bona fide recommendations more
      than elaboration of a true consensus.

PMID- 9759324
TI  - [Treatment of urinary tract infections in neurogenic bladder].
AB  - Urinary tract infections are frequent in children with neurologic bladder.
      Treatment must be adapted to the type of infection: acute pyelonephritis requires
      early intravenous treatment: symptomatic infection of the lower urinary tract is
      to be treated by oral monotherapy; asymptomatic infection needs no treatment.

PMID- 9759325
TI  - [Preventive treatment of urinary tract infections in the child].
AB  - Most of childhood urinary tract infections come through ascending way. Fecal
      microflora is the usual source of the bacterial strains. Infection facilitating
      factors are bacterial virulence which increase bacterial attachment to the
      urinary tract, adhesins and toxins, mostly studied in Escherichia coli, and host
      factors (receptors availability, acquired or congenital urinary tract
      abnormalities). Prophylactic treatment in childhood urinary tract infection is
      indicated in case of obstructed uropathy before surgery, vesico-ureteral reflux
      without surgical management, recurrent cystitis. It includes hygiene, treatment
      of a possible uninhibited bladder, and antimicrobial prophylaxy. Few
      antimicrobial agents have been studied for efficiency and long term tolerance in
      children. Nitrofurantoin and cotrimoxazole are the most currently used.
      Subinhibitory concentrations, about 20% of the curative treatment dosage of lower
      urinary tract infection are effective on bacterial attachment and lessen the
      frequency of infections. They can be given once a day in the evening.

PMID- 9759326
TI  - A genetic switch for long-term memory.
AB  - Current models of brain function hold that learning corresponds to changes in the
      efficacy of single synapses. The study of learning and of a variety of forms of
      synaptic plasticity has revealed that both have at least two phases: an early
      phase that is not dependent on protein synthesis and a late phase that depends on
      new transcription and translation. Our laboratory has examined synaptic
      plasticity in Aplysia and in mice to better understand the regulatory events that
      lead to the induction of the late, protein synthesis-dependent phase of synaptic
      plasticity. Our recent studies of Aplysia have revealed that the genes that
      control the late phase of synaptic facilitation are controlled by both an
      activator, ApCREB1, and a repressor, ApCREB2. This leads to a model in which the
      late phase of synaptic facilitation is initiated by a perturbation of the balance
      between activators and repressors of transcription; this perturbation can be
      accomplished by regulating the activator, the repressor, or both. We, and others,
      have shown that this transcriptional switch is conserved, at least in part, in
      the regulation of synaptic plasticity in mice: CREB is implicated in activation
      of genes required for LTP, a model for synaptic plasticity in the mammalian
      hippocampus. We speculate that a similar balance between activators and
      repressors may regulate the genes required for long-term memory in mammals.

PMID- 9759327
TI  - A molecular biological approach to synaptic plasticity and learning.
AB  - Until the more recent advances made in molecular biology, attempts to link
      synaptic plasticity and learning have focused on using LTP as a marker of
      learning-induced synaptic plasticity, where one has expected to observe the same
      magnitude of change in synaptic strength as that observed with artificial
      stimulation. To a large extent this approach has been frustrated by the fact that
      it is generally assumed that the representation of the memory traces is
      distributed throughout widespread networks of cells. By implication it is more
      likely that one would observe small distributed changes within a network; a
      formidable task to measure. In this review we describe how the advances in
      molecular biology give us both the tools to investigate the mechanisms of
      synaptic plasticity and to apply these to investigations of the underlying
      mechanisms in learning and the formation of memories that have until now remained
      out of our grasp.

PMID- 9759328
TI  - [Brief history of long-term synaptic depression of the cerebellum].

PMID- 9759329
TI  - [Long-term depression of excitatory synapses in the cortex and hippocampus].
AB  - The efficacy of excitatory synapses terminating on cortical and hippocampal
      pyramidal cells may be persistently depressed as well as potentiated. Homo
      synaptic long-term depression (LTD) seems to be triggered by an entry of calcium
      into a post-synaptic cell less than that needed to initiate long-term
      potentiation (LTP). Theoretical work predicted, and experimental studies
      confirmed, that moderate elevations of calcium initiate LTD via a cascade of
      biochemical interactions involving calcium-dependent phosphatases. Genetically
      modified animals confirmed the prediction of a sliding threshold that defines the
      limit between LTD and LTP. While mechanisms for the initiation of LTD are quite
      well established, it remains unclear whether pre- or post-synaptic mechanisms, or
      both, are involved in its maintenance. A role for LTD in processes of learning
      and forgetting in the adult animal remains to be firmly established. It seems
      probable, however, that a persistent reduction in synaptic weight is a basic
      process used in the establishment and refinement of neuronal circuits during
      development.

PMID- 9759330
TI  - Quantal analysis and long-term potentiation.
AB  - Quantal analysis is useful for assessing the pre- and/or post-synaptic locus of
      the expression of long-term tetanic potentiation with the condition, however,
      that the studied synaptic potentials have been evoked by single cell
      stimulations, as is the case with paired recordings of identified neurons. The
      application of this methodology, primarily with indirect criteria, has produced
      conclusions which dance back and forth across the synaptic cleft.

PMID- 9759332
TI  - [Post-lesional plasticity of somatosensory cortex maps: a review].

PMID- 9759331
TI  - Quantal analysis of synaptic processes in the neocortex.
AB  - The application of fluctuation analysis to studies of synaptic function in the
      neocortex is discussed. Analysis of failures of transmission has been valuable in
      indicating whether a presynaptic or a postsynaptic site is responsible for a
      change in synaptic efficacy. When combined with detailed ultrastructural
      verification of all synapses involved in an individual cell to cell connection, a
      reasonable estimate of quantal size and release probability under conditions of
      low frequency activity can be obtained. However, both the number of available
      release sites in functional terms and the probability that an action potential
      (AP) will release transmitter from any given site can vary from AP to AP at
      higher frequencies. A variety of presynaptic mechanisms that modulate release are
      now apparent. For example, one mechanism dominates release patterns at one class
      of connection which is insensitive to absolute firing frequency, but responsive
      to changes in frequency. At another class of connection, a different mechanism
      dominates, resulting in high sensitivity to frequency.

PMID- 9759333
TI  - Memory systems.
AB  - Two recent findings are summarized here that bear on the organization of memory
      and brain systems. First, the capacity for simple recognition of familiarity (a
      form of declarative memory) depends on the hippocampal region in both humans and
      nonhuman primates. Second, probabilistic classification learning (a form of
      nondeclarative memory akin to habit learning) depends on the caudate nucleus and
      putamen. These findings are related to the classification of long-term memory and
      current understanding of the participating brain systems.

PMID- 9759334
TI  - [Olfactory training: memory systems in the rats].

PMID- 9759335
TI  - [Memory consolidation and the hippocampal system].

PMID- 9759336
TI  - Working memory.
AB  - It is suggested that working memory comprises a system for the temporary storage
      and manipulation of information, forming an important link between perception and
      controlled action. Evidence is presented for a three-component model, comprising
      an attentional control system, the central executive, and two subsidiary slave
      systems. One of these the, the visuo-spatial sketch pad holds and manipulates
      spatial information, while the other, the phonological loop performs a similar
      function for auditory and speech-based information. Evidence is presented for the
      view that the phonological loop has evolved as a mechanism to facilitate the
      acquisition of language.

PMID- 9759337
TI  - The relationships between working memory and long-term memory.
AB  - Recent studies have led to the proposal that working memory operates not as a
      gateway between sensory input and long-term memory but as a workspace. The core
      of argument is that access to acquired knowledge and prior learning occurs before
      information becomes available to working memory. This proposition is a way to
      accommodate Baddeley's multiple component working memory model and the view that
      considers that working memory is nothing other than temporary activations of
      representations and procedures in long-term memory. However, this 'workspace'
      conception of working memory raises the question of the relationships between the
      central executive system and long-term memory.

PMID- 9759338
TI  - The associative parietal cortex and spatial processing in rodents.
AB  - It is widely acknowledged that the hippocampal formation has a central function
      in rodents' spatial memory and navigation. However, recent work has shown that
      other structures participate in specific spatial processing. That is so for the
      associative parietal cortex (APC). Although this neocortical region is far less
      developed in rodents than in humans and non-human primates, APC damage in rodents
      induces deficits which affect both egocentrically and allocentrically organized
      spatial behaviours. On the basis of behavioural (following parietal lesions) and
      neuroanatomical data, we propose that the APC could be at the interface between
      the level of perception of the physical world (egocentrically organized) and that
      of representations or maps (allocentrically organized) of this world.
      Reciprocally, the APC could also be involved in the transformation, in the
      opposite direction, of computations made on the basis of representations into
      motor actions necessary for the efficient execution of oriented behaviours within
      the physical world.

PMID- 9759339
TI  - Backward signal from medial temporal lobe in neural circuit reorganization of
      primate inferotemporal cortex.
AB  - Neuropsychological theories proposed a critical role of the interaction between
      the medial temporal lobe and neocortex in the formation of long-term memory for
      facts and events, which has often been tested by learning of a series of paired
      words or figures in humans. We identify neural mechanisms of this long-term
      memory formation process by single-unit recording and molecular biological
      methods in an animal model of visual pair-association task in monkeys. In our
      previous studies, we found a group of neurons that manifested selective responses
      to both of the paired associates (pair-coding neuron) in the anterior inferior
      temporal (IT) cortex. It provides strong evidence that single IT neurons acquire
      the response-selectivity through associative learning, and suggests that the
      reorganized neural circuits for the pair-coding neurons serve as the memory
      engram of the pair-association learning. In this article, we investigated further
      mechanisms of the neural circuit reorganization. First, we tested the role of the
      backward connections from the medial temporal lobe to IT cortex. Ibotenic acid
      was injected unilaterally into the entorhinal and perirhinal cortex which
      provided massive backward projections ipsilaterally to IT cortex. We found that
      the limbic lesion disrupted the associative code of the IT neurons between the
      paired associates, without impairing the visual response to each stimulus.
      Second, we ask why the limbic-neocortical interactions are so important. We
      hypothesize that limbic neurons would undergo rapid modification of synaptic
      connectivity and provide backward signals that guide reorganization of
      neocortical neural circuits. We then investigated the molecular basis of such
      rapid synaptic modifiability by detecting the expression of immediate-early
      genes. We found strong expression of zif268 during the learning of a new set of
      paired associates, most intensively in area 36 of the perirhinal cortex. All
      these results with visual pair-association task support our hypothesis, and
      demonstrate that the 'consolidation' process, which was first proposed on the
      basis of clinico-psychological evidence, can now be examined in the primate with
      neurophysiolocical and molecular biological approaches.

PMID- 9759340
TI  - Learning by neurones: role of attention, reinforcement and behaviour.
AB  - The importance of the behavioural situation, attentional demands of the task, and
      stimulus-reinforcement contingencies in promoting or permitting experience
      dependent neuronal plasticity is argued. Evidence is provided for the specific
      activation of the locus coeruleus noradrenergic system of the rat by novel
      stimuli encountered while investigating the environment, as well as during a
      formal learning situation. Noradrenergic neurons are particularly concerned with
      changes in the predictive value of the stimulus, when new learning should occur.
      Noradrenaline, released at LC terminals in target sensory systems, could
      facilitate shifts in attention, information processing and memory through its
      well-documented gating and tuning effects and its permissive role in long-term
      potentiation. Dopamine neurons, which fire persistently to reward during
      learning, could be involved in maintaining the behavioural response.

PMID- 9759341
TI  - Brain imaging and memory systems in humans: the contribution of PET methods.
AB  - The development of neuroimaging methods such as PET, has provided a new impulse
      to the study of the neural basis of cognitive functions, and has extended the
      field of inquiry from the analysis of the consequences of brain lesions to the
      functional investigations of brain activity, either in patients with selective
      neuropsychological deficits or in normal subjects engaged in cognitive tasks.
      Specific patterns of hypometabolism in neurological patients are associated with
      different profiles of memory deficits. [18F]FDG PET studies have confirmed the
      association of episodic memory with the structures of Papez's circuit and have
      shown correlations between short-term and semantic memory and the language areas.
      The identification of anatomo-functional networks involved in specific components
      of memory function in normal subjects is the aim of several PET activation
      studies. The results are in agreement with 'neural network' models of the neural
      basis of memory, as complex functions subserved by multiple interconnected
      cortical and subcortical structures.

PMID- 9759342
TI  - Is PET solely a post-hoc tool to validate psychological models of memory?

PMID- 9759343
TI  - The pharmacology of memory.
AB  - Neurotransmitters play a critical role in the brain circuits involved in various
      aspects of memory. The importance of acetylcholine is illustrated by the
      psychopathology of Alzheimer's disease. Cholinergic replacement therapy is now
      available for treating the cognitive decline associated with this form of
      degenerative disease. Dopamine in the prefrontal cortex also contributes to
      information storage, particularly working memory. In both cases efforts have been
      made to identify the receptor subtype involved and such information is essential
      if pharmacologically specific drugs are to be developed for cognitive
      enhancement.

PMID- 9759344
TI  - 5-HT4 receptors: long-term blockade of K+ channels and effects on olfactory
      memory.

PMID- 9759345
TI  - [The decrease in the hippocampus of the neurosteroid pregnenolone sulfate is
      involved in memory deficit in the aged animal].

PMID- 9759347
TI  - [For a "neurocognitive" approach to memory: value of neuropsychology].
AB  - Cognitive models suggest that memory consists of potentially independent modules.
      In addition, clinical data lead to a reference to the central systems that
      interact with these operative modules, and which assign significance and
      pertinence to the information being processed. Such an organization fits better
      with clinical data, since it can be demonstrated with the example of episodic or
      procedural memories as both require the activation of strategic processes, under
      the control of the prefrontal cortex, needed for the organization or the control
      of the information to be processed.

PMID- 9759346
TI  - [Memory disorders: from lesional deficit to functional disorders].
AB  - The purpose of this presentation of pathological data is to demonstrate how our
      ideas have developed from a chronological point of view to our present interest
      in elementary cognitive processes. The present relative rarity of significant
      data in brain imagery, compared with what is observed in other fields of neuro
      psychology, is probably due to the complexity of this cognitive processes.

PMID- 9759348
TI  - Hierarchical neuronal modeling of cognitive functions: from synaptic transmission
      to the Tower of London.
AB  - Recent progress in the molecular biology of synaptic transmission, in particular
      of neurotransmitter receptors, offers novel information relevant to 'realistic'
      modeling of neural processes at the single cell and network level. Sophisticated
      computer analyses of 2D crystals by high resolution electron microscopy yield
      images of single neurotransmitter receptor molecules with tentative
      identifications of ligand binding sites and of conformational transitions. The
      dynamics of conformational changes can be accounted for by a 'multistate
      allosteric network' model. Allosteric receptors also possess the structural and
      functional properties required to serve as coincidence detectors between pre- and
      post-synaptic signals and, therefore, can be used as building blocks for a
      chemical Hebb synapse. These properties were introduced into networks of formal
      neurons capable of producing and detecting temporal sequences. In more elaborate
      models of pre-frontal cortex functions, allosteric receptors control the
      selection of transient 'pre-representations' and their stabilization by external
      or internal reward signals. We apply this scheme to Shallice's Tower of London
      test, and we show how a hierarchical neuronal architecture can implement
      executive or planning functions associated with frontal areas.

PMID- 9759350
TI  - Memory, learning and metacognition.

PMID- 9759349
TI  - Modeling memory: what do we learn from attractor neural networks?
AB  - In this paper we summarize some of the main contributions of models of recurrent
      neural networks with associative memory properties. We compare the behavior of
      these attractor neural networks with empirical data from both physiology and
      psychology. This type of network could be used in models with more complex
      functions.

PMID- 9759351
TI  - Accelerated cyclization of lambda DNA.
AB  - In the presence of spermidine, the DNA molecule of the bacteriophage lambda
      undergoes a coil-globule transition. We report here that the cyclization of this
      molecule in its globular state is greatly accelerated (by more than 10(4)-fold)
      in comparison with the cyclization reaction taking place in the coil
      conformation.

PMID- 9759352
TI  - [Effect of halogenated quaternary ammonium on cultured tumor cells].
AB  - This work reports the action of one halogenic quaternary ammonium compound on the
      in-vitro proliferation of different lines of human cancer cells. IC 50 inhibition
      growth was observed at a concentration of 2.10(-6) mol and T1 growth at 3.10(-6)
      5.10(-5) mol. These results seem to indicate that halogenic quaternary ammoniums
      present a potent growth inhibitory activity on different cancer cells lines. The
      presence of a quaternary ammonium group, responsible for some alkylating effect,
      could explain such a result.

PMID- 9759353
TI  - Atypical microtubule organization in undifferentiated human colon cancer cells.
AB  - We previously reported that undifferentiated colonic cancer HT-29 cells, unlike
      the differentiated ones, exhibit unusual organelle distributions and atypical
      vesicle trafficking patterns, which are microtubule-independent and microfilament
      dependent. In the present study, we have analyzed the microtubule network in both
      phenotypes, using confocal microscopy, and determined the expression levels of
      some microtubule-associated proteins by quantitative immunoblotting.
      Differentiated cells exhibited the microtubular organization of polarized
      epithelial cells. Non-polarized undifferentiated cells presented an atypical
      microtubule organization as microtubules were localized mainly at the cell 'top'.
      Immunoblot analysis indicated the absence or low content of several structural
      and motor microtubule-associated proteins in undifferentiated cells, compared to
      differentiated cells. This may explain in part their atypical microtubular
      organization. This study agrees with a crucial role for microfilaments in the
      intracellular organization of undifferentiated HT-29 cancer cells, while
      differentiated HT-29 cells exhibit intracellular organization similar to that of
      normal enterocytic cells, although they are also tumoral.

PMID- 9759354
TI  - An accessory peptide binding site with allosteric effect on the formation of
      peptide-MHC-II complexes?
AB  - MHC-II molecules bind a single peptide in their groove. Here, the authors
      summarise evidence that a second peptide could bind transiently to MHC-II
      molecules outside the groove and have an allosteric effect on peptide-MHC-II
      complex formation. This effect could modulate, after the antigen processing, the
      selection of the peptide subset presented by MHC-II molecules to the helper CD4 T
      cells, which regulate the specific immune response.

PMID- 9759355
TI  - High protection by grape seed proanthocyanidins (GSPC) of polyunsaturated fatty
      acids against UV-C induced peroxidation.
AB  - The antioxidative effects of grape seed proanthocyanidins (GSPC) were studied in
      three in-vitro models in which polyunsaturated fatty acids (PUFAs) in aqueous
      solution and mice liver or brain microsomes were used as oxidative substrates,
      and UV-C irradiation as the pro-oxidant system. Analysis of UV-C induced lipid
      peroxidation was carried out by two methods: gas liquid chromatography of
      residual PUFAs and release of thiobarbituric acid-reactive substances (TBARs)
      measured by TBA reaction. Results indicate that PUFAs are more radiosensitive
      when incorporated in single component micelles than in mixed component micelles
      or microsomes. In every case, PUFA peroxidation was inhibited by low
      concentrations of GSPC (2 mg/L) while epigallocatecin (EGC) and epigallocatechin
      gallate (EGCG) monomers, at an equivalent level of epicatechin, exhibited no
      efficacy in our experimental conditions. This latter effect might be explained by
      a synergistic action of flavan-3-ol monomers, dimers and oligomers contained in
      the grape seed extract.

PMID- 9759356
TI  - Origin and evolution of Asian hominoid primates. Paleontological data versus
      molecular data.
AB  - The origin and evolution of hominoid primates (apes and man) has long been
      studied exclusively on the basis of available fossil remains. Indeed, a migration
      of African primates towards Asia at about -16 to -17 Ma might have given the
      lineage of Miocene Asian hominoids. This hypothesis is supported by the oldest
      remains of Miocene Asian hominoids dated at about -16.1 Ma. But the recent
      discovery of anthropoid primates in the Eocene of Asia seems to indicate that
      Asia was a major evolutionary and differentiation centre for anthropoid primates
      as early as the Eocene. In addition, Asian primates probably continued to evolve
      in Asia from the Eocene onward and led at least to the extant Asian hominoids
      (orangutans and gibbons). African and Asian extant anthropoid primates might
      therefore have diverged at least 36 Ma ago, and this hypothesis is also supported
      by the most recent data in molecular biology. Moreover, an Asiatic origin of
      African Paleogene propliopithecine primates is suggested. In that context,
      evolutionary rates might not be constant, and molecular clocks should be
      necessarily characteristic for each studied group of mammals. Several examples
      that illustrate the conflict between paleontological and molecular data are
      discussed. The necessity to integrate more systematically paleontological data as
      chronological reference points in studies in molecular phylogeny is discussed.

PMID- 9759358
TI  - [Tissue selectivity of calcium channel blockers].
AB  - Calcium channel blockers are also termed calcium antagonists or calcium entry
      blockers. The use of calcium antagonists for the management of hypertension is
      well established. Their control of vascular tone is related to their interaction
      with the alpha 1 subunit of L-type calcium channels. This interaction is not
      simple since prolonged depolarisation promotes the inactivated state of the
      channels resulting in a change of affinity which is different for various
      molecules so far considered. The isoforms of alpha 1 subunits and the duration of
      the stimulus required to activate heart or vessels are important parameters to be
      considered with the nature of the molecule. Those parameters influence the
      vascular selectivity which is quantified as the ratio of the concentrations
      required to reduce by 50% the contraction of heart and of vessels. This
      selectivity is an important component in the therapeutic action. Another
      component of this action is the prevention of structural changes noted in heart
      and arteries. As well as lowering blood pressure, calcium channel blockers have
      also been found to exert blood pressure independent effects. For instance, they
      reduce cardiac and vascular hypertrophy and avoid renal damage. In the stroke
      prone rat, such protective effects are accompanied by reduction of the salt
      dependent overexpression of the gene of endothelin-1 and of fetal genes
      associated with cardiac hypertrophy. This paper summarizes available information
      about those components and discuss their significance.

PMID- 9759357
TI  - [Paleogenetic analysis of the skeletons from the sepulchral cave of Elzarreko
      Karbia (Bronze Age, Basque Country)].
AB  - Through paleogenetic studies we have characterised the sampling of a sepulchral
      cave named Elzarreko Karbia, in the Basque Country (France). Four people had been
      buried in this cave in the Ancient Bronze Age, three men, including an
      adolescent, and a woman, dating from 3,700 BP. In addition to a confirmation of
      the anatomical sex determination through amelogenin first intron amplification,
      we obtained a mitochondrial second hypervariable region (HVR II) sequence for
      each individual, and thus, we excluded maternal relationship between some of the
      skeletons.

PMID- 9759359
TI  - [Physiopathology of calcium channels: identification of calcium channelopathies].
AB  - Since a few years, many mutations in genes encoding voltage-dependent ion
      channels have been identified. The related disorders are quoted as
      "channelopathies". These mutations are responsible for several skeletal muscle,
      brain, heart or kidney diseases. Abnormal calcium channels genes are responsible
      for hypokaleamic periodic paralysis (CACNA1S) as well as some forms of ataxia,
      cerebellar degeneration and migraine (CACNA1A). The preliminary studies of the
      recently discovered calcium channelopathies are undergoing. Both in vitro and in
      vivo studies of the diseased genes should help to the understanding of the
      related pathologies as well as to extend our knowledge of calcium channel
      function. In addition, autoantibodies against calcium channels are retrieved in
      some autoimmune diseases, such as Lambert-Eaton myasthenic syndrome (LEMS).
      Complementary studies are necessary to identify the precise implication of
      calcium channels in these auto-immune channelopathies.

PMID- 9759360
TI  - [Intracellular calcium channels, hormone receptors and intercellular calcium
      waves].
AB  - The hormone-mediated intercellular Ca2+ waves were analyzed in multiplets of rat
      hepatocytes by video imaging of fura2 fluorescence. These multicellular systems
      are composed of groups of several cells (doublets to quintuplets) issued from the
      liver cell plate, a one cell-thick cord of about 20 hepatocytes long between
      portal and centrolobular veins. When the multiplets were homogeneously bathed
      with the glycogenolytic agonists vasopressin, noradrenaline, angiotensin II and
      ATP, they showed highly organized Ca2+ signals. Surprisingly, for a given
      agonist, the primary rises in intracellular Ca2+ concentration ([Ca2+]i)
      originated invariably in the same hepatocyte, then was propagated in a sequential
      manner to the nearest connected cells (cell 2, then 3, cell 4 in a quadruplet,
      for example). The sequential activation of the cells appeared to be an intrinsic
      property of multiplets of rat hepatocytes. The same sequence was observed at each
      train of oscillations occurring between cells. The order of [Ca2+]i responses was
      modified neither by repeated additions of hormones nor by the hormonal dose. The
      mechanical disruption of an intermediate cell did not prevent the activation of
      the next cell. These results suggest that each hepatocyte in the multiplet
      displays its own sensitivity to the hormone and that a gradient of sensitivity
      between each cell could be responsible for directing the intercellular Ca2+ wave.
      To test this hypothesis, we selectively isolated rat hepatocytes from periportal
      (PP) and perivenous (PV) areas of the liver cell plate. Periportal (PP) and
      perivenous (PV) rat hepatocyte suspensions were loaded with quin2/AM and hormonal
      responses were studied in a spectrofluorimeter. Noradrenaline, angiotensin II,
      and vasopressin-induced [Ca2+]i rises were greater in PV than in PP hepatocytes.
      In contrast, PP cells were more responsive than PV cells to ATP. The function of
      the InsP3 receptor (InsP3R) was also studied by measuring the InsP3-mediated
      45Ca2+ release from permeabilized PP and PV hepatocytes. In permeabilized PP and
      PV hepatocytes, internal Ca2+ stores displayed the same loading-kinetics, the
      responses to InsP3 were similar, and the sizes of InsP3-sensitive compartment
      were not different. In a further study, we investigated by video microscopy in
      fura2-loaded multicellular systems of rat hepatocytes, the mechanisms controlling
      intercellular propagation of the Ca2+ wave and coordination of Ca2+ signals
      induced by the different hormones. Using focal microperfusion which allows local
      perfusion of any cell of the multiplet, rapid agonist removal during the Ca2+
      response and microinjection, we found that second messengers and [Ca2+]i rises in
      one hepatocyte cannot trigger Ca2+ responses in connected adjacent cells,
      suggesting that diffusion across gap junctions, while required for coordination,
      is not sufficient by itself for the propagation of the intercellular Ca2+ wave.
      In addition, focal microperfusion and intermediate cell disruption experiments
      revealed very fine functional differences (hormonal delay, frequency of [Ca2+]i
      oscillations) between hormone-induced Ca2+ signals, even between two adjacent
      connected hepatocytes. Recent unpublished results performed in suspensions of PP
      and PV rat hepatocytes supported the view of a major role played by vasopressin
      receptors (V1a) in genesis and orientation of the Ca2+ wave. Vasopressin binding
      sites, V1a mRNAs detected by RNAse Protection Assay, and vasopressin-induced
      InsP3 production, were more abundant in PV than in PP cells. A gradient of
      hormone receptors could orientate the propagation of the Ca2+ wave in
      multicellular systems and in liver cell plate. These results suggest that the
      intercellular Ca2+ wave in multicellular systems of rat hepatocytes is propagated
      through mechanisms involving at least three factors. (ABSTRACT TRUNCATED)

PMID- 9759362
TI  - [Drawing movements and gravitational force: central or peripheral regulation?].
AB  - Drawing arm movements in four different directions: a) upward vertical (0
      degree), b) upward oblique (45 degrees), c) downward vertical (180 degrees) and
      d) downward oblique (135 degrees), and at two different speeds, normal and fast,
      were executed by eight subjects. Movements of the arm were recorded using an
      optoelectronic (2 TV, 100 Hz) system which allowed the computer reconstruction of
      joint motion. Analyses focused upon pen kinematics in the frontal plane. Velocity
      profiles were unimodal for all conditions. The ratio of acceleration time to
      total movement time changed significantly as a function of the direction and the
      speed of the movement. Movement time and was not affected by movement direction
      and consequently changes in gravitational torques, for both speeds tested.
      Results from this study provide indirect evidence that the CNS executes movements
      by taking advantage of gravitational force.

PMID- 9759361
TI  - [Astrocytes and lentivirus infection in an experimental models of macaque
      infected with SIVmac251].
AB  - The present study demonstrates the susceptibility of astrocytes to infection with
      SIVmac251. Indeed, primary cultures of astrocytes derived from simian adult
      brains, can be infected in vitro with the SIVmac251. Results show that SIVmac251
      establishes a persistent infection in primary astroglial cultures and that viral
      replication can be reactivated by TNF-alpha, GM-CSF, IFN-gamma. Viral proteins as
      Nef, Rev, Vpx and occasionally gp120/160 are evidenced by immunocytochemistry. In
      vivo SIVmac251 and/or HIV-2 infected astrocytes have been isolated from brains of
      macaques following ex vivo primary cultures. The whole of these results
      demonstrated that, in this model, SIV establishes a persistent state of infection
      of astrocytes, that viral replication can be reactivated by cytokines and
      moreover suggest strongly an in vivo infection of astrocytes in the brain of
      these infected macaques.

PMID- 9759363
TI  - [Recovery of muscle contractility after a strength training session: mechanical,
      neurophysiologic and biochemical approach].
AB  - The purpose of this study was to observe the recovery of maximal strength
      immediately after a maximal eccentric strength training set. The trained female
      subjects (n = 8) performed 10 bouts of 10 maximal eccentric contractions of the
      quadriceps muscle. Each bout was separated by a 2 minutes rest period. Integrated
      electromyogram (iEMG) of the vastus medialis and the rectus femoris, and torque
      were measured before, just after, 24 and 48 hours after training session, at
      different knee angular velocity (-60, 0, 60, 120, and 240 degrees.s-1). Possible
      structural damage of the muscular cell were searched from the urinary
      concentration of some protein catabolism metabolites before (basal rate), 24 and
      48 hours after the exercise. Maximal torque significantly fell for any angular
      velocity immediately after the training session: 13.6% at -60 degrees.s-1, 16.9%
      at 60 degrees.s-1, 7.5% at 120 degrees.s-1, 12.8% at 240 degrees.s-1 and 8.6% at
      0 degree.s-1. This event was accompanied by an increase of the iEMG at the
      training angular speed, and by an increase of the metabolites concentration in a
      half part of the subjects. Strength developed during eccentric contraction showed
      the earliest recovery. And it even significantly overshot its initial level by
      14.9% at 48 hours. A significant increase of the iEMG assessed at the eccentric
      velocity was then observed. In the same time, 3 of the 6 subjects showed an
      increase of their urinary concentration of the chosen metabolites in comparison
      with their initial values. This result may closely be connected with the
      supercompensation phenomenon, which first appears in the training mode. This
      phenomenon could partly be explained by the associated increase of the iEMG.

PMID- 9759364
TI  - [Similarities between angiogenesis and neoplasm invasiveness ].
AB  - We have shown that given cytokines are capable of inducing the expression of
      transcription factors of the Ets family in two very distinct cell types: 1)
      endothelial cells of blood vessels, but only during neovascularization, and 2)
      fibrocytic cells from stroma surrounding tumors, but only if these tumors bear
      characteristics of invasiveness. In such cases, the fibrocytic cells also express
      some metalloproteinases (collagenase 1, urkinase plasminogen activator, sometimes
      stromelysin1). In ex vivo reconstruction experiments, we demonstrate that the
      corresponding genes are directly up-regulated by the Ets family transcription
      factors, often associated with the transcription complex Jun/Fos. The proteinases
      are thought to dismantle the stroma and allow invasive tumors to proceed toward
      further expansion. We speculate that inactivation of the Ets factors could
      seriously hamper both neovascularization and tumor expansion.

PMID- 9759366
TI  - [The alpha-catenin gene is a suppressor gene of neoplasm invasiveness].

PMID- 9759365
TI  - [Cyclin A: a good markers for the study of cell cycle control and tumor
      progression?].
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 conducted in established cell lines and
      in primary human T lymphocytes, have demonstrated that the promoter of its gene
      is under negative transcriptional control in quiescent cells. The DNA sequences
      mediating this repression have been delineated through in vitro mutagenesis as
      well as in vivo genomic footprinting experiments. Indirect observations suggest
      the involvement of proteins related to the retinoblastoma tumor suppressor
      protein (pRb). Using primary fibroblasts from either pRb(-/-), p107(-/-), p130(-/
      ) or p107(-/-)/p130(-/-) mice, we show in this work that mutation of the pRb gene
      has the more profound effect on cyclin A transcription. Finally, normal
      fibroblasts cultured in suspension fail to express cyclin A and can no longer
      enter S phase and proliferate, revealing thus a dependence of cyclin A expression
      on cell anchorage. Our work suggests the existence of at least two sets of
      regulators controlling cell cycle progression. On the one hand, proteins like
      cyclin D1, whose expression is a direct consequence of the activation of the ras
      signalling pathway and on the other hand, proteins like cyclin A which are
      secondary response effectors. As a result, growth factor stimulation leads to a
      transcriptional activation of the former set, while the transcription of the
      latter set is under the control of a repressor whose effect is alleviated after
      triggering the ras cascade. The status of pRb thus dictates whether cells
      continue their progression through the cell cycle when ras is mutated, probably
      by allowing the uncontrolled expression of critical genes like cyclin A.

PMID- 9759367
TI  - [Is hereditary predisposition to breast cancer linked to BRCA1 a disease of
      response to genotoxic lesions?].
AB  - Germline mutations in either the BRCA1 or the BRCA2 gene are responsible for the
      majority of hereditary breast cancers. The proposition that BRCA1 may play a role
      as a caretaker of the genome, was first put forward by the demonstration that, in
      mitotic and meiotic cells, BRCA1 can interact with Rad51, a major actor in repair
      and/or recombination processes. From there, a fair body of observations have
      converged to support the concept that BRCA1 and BRCA2 play a role in monitoring
      and/or repairing DNA lesions. The relaxation in this monitoring, due to mutations
      of either of these two genes, leaves unrepaired events and leads to the
      accumulation of mutations and ultimately to cancer. Understanding the precise
      biochemical function of BRCA1 and BRCA2 should provide basis for early diagnosis
      and prevention in women carrying a predisposition to breast cancer.

PMID- 9759368
TI  - [Extracellular proteases of stromal origin: contribution to tumor progression and
      therapeutic perspectives].
AB  - For a long time, extracellular proteinases were thought to be expressed by the
      cancerous cells and only able to cleave extracellular matrix components, in order
      to promote tumor cell invasion. Recent works have now demonstrated that these
      proteinases are currently synthesized by stromal fibroblastic cells and that some
      of them may exhibit additive function(s). These findings lead to a new
      therapeutical concept leading to target the activity of stromal proteinases, and
      most notably of the matrix metalloproteinases.

PMID- 9759369
TI  - [Oncogenic factors of metastatic dissemination in neuroblastoma].
AB  - Disseminated neuroblastoma frequently show a very poor prognosis. N-myc gene
      amplification, 1p deletion and lack of CD44 gene expression, are all genetic
      factors associated with the disease's dissemination. Human neuroblastoma
      xenografts in nude mice has permitted to characterize, in disseminated
      neuroblasts, oncogenes overexpression, inactivation of tumor suppressor genes as
      well as detoxifying genes activation which contributes to increase cellular
      resistance to chemotherapy. These genetic abnormalities permit to propose a
      nosology of this very aggressive pediatric solid tumor. Hopefully, this genetic
      classification could be of great value for new therapeutic approaches.

PMID- 9759371
TI  - [Clinical implications of spontaneous and iatrogenic dissemination of tumor cells
      in patients with primary liver cancer].
AB  - Prognosis of patients with primary liver cancer (PLC) often depends on tumor
      recurrence and development of extrahepatic metastases, particularly after liver
      transplantation. We have developed a sensitive test detecting both spontaneous
      circulation of tumor cells and spread of liver cells due to chemoembolization and
      alcoholization. By RT-PCR we looked for cells expressing alphafetoprotein (AFP)
      mRNA in peripheral blood of 84 patients with PLC and 102 controls (55 patients
      with chronic hepatitis and/or cirrhosis, 10 patients with benign liver tumors or
      liver metastases from intestinal cancers and 37 healthy individuals). By spiking
      blood of healthy volunteers with HepG2 cells we assessed the sensitivity limit:
      one HepG2 cell mixed with 10(7) leucocytes. All 102 controls scored negative. In
      contrast, 28 patients (33.3%) with PLC scored positive. Positivity for the test
      was significantly associated with portal thrombosis, tumor size, intravascular
      tumor emboli, serum AFP level and extrahepatic metastases. Patients were followed
      up for a mean period of 39 +/- 51 weeks: the probability of developing
      extrahepatic metastases was significantly higher in positive than in negative
      patients. Eighteen negative patients with PLC were tested before, one hour and 24
      hours after loco-regional therapy: 9 scored positive either one or 24 hours after
      alcoholization or chemoembolization. In conclusion, we have developed a highly
      specific and sensitive test to detect circulating tumor cells in patients with
      PLC. This test is likely to be clinically useful to evaluate the risk of
      developing extrahepatic metastases. Finally, we are developing new strategies to
      characterize cells iatrogenically spread into the blood and to define their
      metastatic potential.

PMID- 9759370
TI  - [Arsenic and retinoic acid, toward targeted treatments of acute promyelocytic
      anemia?].
AB  - Acute promyelocytic leukaemia is a key model system in cancer biology. Its
      exquisite sensitivity to retinoic acid constitutes the first example of
      differentiation therapy. The PML/RAR alpha fusion protein generated by the t(34,
      35) translocation is the molecular basis of transformation. PML/RAR alpha induces
      transformation most likely through a dominant negative interference with the
      function of nuclear receptors leading to a differentiation block. The fusion
      protein also delocalises PML and other nuclear body antigens and this alteration
      of nuclear protein traffic seems to play a role in growth control and apoptosis.
      The clinical response of this disease to retinoids and arsenic trioxide, both of
      which induce the degradation of the fusion protein, constitute the first example
      of a therapy directly targeted to a specific genetic lesion in a human cancer.

PMID- 9759372
TI  - [Polysialylated NCAM in CSF, a marker for invasive medulloblastoma].
AB  - We described a double-site enzyme-linked immunosorbent assay (ELISA) to measure
      polysialic acid neural cell adhesion molecule (PSA-NCAM) level in CSF.
      Immunocapture of PSA-bearing molecules is first effected by means of a monoclonal
      antibody (anti-MenB), directed against sialic acid polymers and adsorbed into
      plastic wells. Linked PSA-NCAM is then revealed by means of a second antibody,
      directed against an aminoacid sequence of NCAM and labelled with peroxydase. The
      lowest amount of PSA-NCAM detectable was estimated to be 0.11 microgram/l. This
      value was considered as the threshold for positivity. PSA-NCAM level was measured
      using this method in CSF from 29 patients with medulloblastoma. CSF had been
      collected at different times following tumor excision and stored at--80 degrees
      C. At the same times, cytological examination in CSF (medulloblastoma metastatic
      cells) and craniospinal imaging (tomographic scan or MRI) had been performed. PSA
      NCAM was never detected in control CSF. For patients in remission, beyond the
      post-operative period of 1 or 2 months, 18 on 21 exhibited a PSA-NCAM level below
      the threshold value. For refractory patients, so classified according to the
      positivity of cytology and/or imaging, whatever the time after the tumor
      excision, PSA-NCAM was always positive (23/23), while either cytology or imaging
      were positive less frequently (16/23 for both). For relapses, PSA-NCAM was more
      frequently positive (6/7) than cytology and imaging (1/7 and 5/7, respectively).
      We concluded that PSA-NCAM positivity in CSF may be a reliable marker to detect
      the invasive or metastatic feature of medulloblastoma.

PMID- 9759373
TI  - [Synthetic peptide as retinoid vector and antiproliferative agent].
AB  - First part: Structure, conformational behaviour and vectorization properties of a
      peptide (PFNLS) designed by association of a fusion peptide and a nuclear
      localization sequence is described. Tryptophan fluorescence quenching
      measurements show that ten peptide molecules bind one all trans retinol or all
      trans retinoic acid molecule with a strong affinity (Kd' = 40 nM). And is able to
      help the internalization of all-trans retinol in human fibroblasts.
      Stoichiometry, structure and affinity of the binding can be compared with those
      of cellular retinoid binding proteins (CRBP), the structure of which is an
      antiparallel beta barrel. Second part: Cytotoxic properties of the amphiphilic
      synthetic peptide are presented. Comparative analysis of proliferating,
      differentiated and confluent H9C2 adherent cells shows a correlation between
      toxicity and cell cycle stage (proliferating cells). Electrophysiological
      measurements on Xenopus laevi oocytes bathed in the peptide also demonstrate the
      induction of cationic currents, which are voltage dependent. These results allow
      us to hypothesize that the observed toxicity is related to membrane
      hyperpolarization of proliferating cells at the G1/S cell cycle phase transition.
      An important point is that in the case of the "peptide-retinoid" complex, no
      cytotoxicity is observed.

PMID- 9759374
TI  - [Effects of HGF on the production of matrix metalloproteinases by colonic cancer
      cells DHD/K12].
AB  - Matrix metalloproteinases (MMPs) and growth factors such as hepatocyte growth
      factor (HGF) are implicated in tumoral progression of several digestive cancers.
      The rat DHD/K12 colonic cancer cell line is very invasive in vivo. We showed by
      RT-PCR and western immunoblotting the presence of HGF receptor, c-Met, in DHD/K12
      cells. Then, we detected by zymography and western blots the secretion of MMP-2
      and MMP-9 in the conditioned medium of these cells. After 24 or 48 h of culture
      in medium supplemented with HGF, transforming growth factor-alpha (TGF-alpha) or
      sodium butyrate, MMP production by DHD/K12 cells was stimulated by HGF and TGF
      alpha and inhibited by sodium butyrate. Knowing the capacity of MMPs to degrade
      the extracellular matrix and thus to favour tumoral invasion, results suggest
      that HGF is implicated in the aggressive behaviour of DHD/K12 cells since it
      increased MMPs secretion by these cells.

PMID- 9759375
TI  - [Mechanisms of action and cellular functions of molecular motors].
AB  - Cytoskeleton based molecular motors support most of the cellular movements and by
      consequence they are associated with a variety of human disorders. The wide
      functional diversity of these molecular motors is now explained by the presence
      of three different families: the myosin, kinesin and dynein families. Although
      they are functionally distinct, these motors present unexpected structural
      homologies at the ATP and actin or microtubule binding sites. However, these
      homologies do not seem sufficient to design a common molecular mechanism which
      allows these proteins to move along the cytoskeleton.

PMID- 9759376
TI  - [Molecular dynamics of annexin I in normal and infected cells].
AB  - Annexins are a family of proteins present within the tissues of all multicellular
      organisms, mammalian erythrocytes excepted. The property shared by all annexins
      is the calcium and membrane binding. Annexins are constituted of two domains. The
      N-terminal domain gives the molecule its specificity and the C-terminal domain,
      highly conserved, containing 4 repetitions of 70 amino-acids, gives the common
      properties. Although numerous important works were performed, the exact function
      of annexins is not unraveled. They participate to many cellular processes as for
      instance exocytosis, endocytosis or phagosome maturation. Many hypotheses,
      supported by experimental results, have been proposed. In this review, we propose
      a summary of the principal characteristics of annexins and we discuss the main
      hypotheses proposed for their functions.

PMID- 9759377
TI  - [Tyrosine kinases of the Src family, enzymes with multiple functions: from the
      growth of fibroblasts to the migration of epithelial cells].
AB  - The tyrosine kinases of the Src family were first discovered due to their
      oncogenic properties. In untransformed fibroblasts, these kinases are activated
      as cells exists quiescence in response to some growth factors. Using
      microinjection to introduce catalytically inactive dominant-negative form of
      cSrc, as well as an antibody that neutralizes cSrc, Fyn and cYes, we have shown
      that Src kinases are required for DNA synthesis induced by most growth factors
      (PDGF, EGF, CSF-1, insulin, IGF-1). A functional link between Src kinases and the
      expression of the transcription factor c-Myc was also shown. In addition to cell
      growth promotion, some factors induce epithelial cell scattering and this also
      requires cSrc and cYes activities. However, in contrast to mitogenesis, they do
      not need novel gene expression for signalling but rather may act by
      phosphorylating components that regulate the cytoskeleton. Finally, increased Src
      kinase activities were found in several human carcinomas and we propose that
      these enzymes are involved in cell invasion.

PMID- 9759378
TI  - [Role of the multifunctional Trio protein in the control of the Rac1 and RhoA
      gtpase signaling pathways].
AB  - The small GTPases Cdc42, Rac and RhoA have important regulatory roles in
      mediating cytoskeletal rearrangements, MAP kinase cascades and induction of G1
      cell cycle progression. The activity of the GTPases is regulated by guanine
      nucleotide exchange factors (GEFs) which accelerate their GDP/GTP exchange rate,
      and thereby activate them. All the GEFs for the Rho-GTPases family share two
      conserved domains: the DH domain (for Dbl-homology domain) responsible for the
      enzymatic activity, and the PH domain, probably responsible for the proper
      localization of the molecule. Trio is a multifunctional protein that is comprised
      of two functional Rho-GEFs domains and a serine/threonine kinase domain. We have
      shown in vitro and in vivo that the first GEF domain (GEFD1) activates Rac1,
      while the second GEF domain (GEFD2) acts on RhoA. Moreover, the co-expression of
      both domains induces simultaneously the activation of both GTPases. To our
      knowledge, this is the first example of a member of the Rho-GEF family, that
      contains two functional exchange factor domains, with restricted and different
      specificity. We are currently investigating how these GEF domains are activated,
      by addressing the role of the PH domains in GTPases activation by Trio. We have
      shown that: 1) the PH1 of Trio is necessary for Rac activation by the GEFD1; 2)
      the PH1 of Trio targets the molecule to the cytoskeleton; 3) the GEFD1 domain of
      Trio binds, in a two-hybrid screen, the actin binding protein filamin. These data
      suggest that the PH1 targets Trio to the cytoskeleton close to Rac and its
      effectors, probably via interaction with the actin-binding protein filamin,
      consistent with a role of Trio in actin cytoskeleton remodeling.

PMID- 9759379
TI  - [Raymond Latarjet, a scientist of the century].

PMID- 9759380
TI  - [Algal toxins, inhibitors of serine/threonine phosphatases].
AB  - Under certain environmental conditions, marine and freshwater phytoplankton may
      produce phycotoxins inhibitors of serine/threonine protein phosphatases 1, 2A and
      3. In the marine environment, dinoflagellates produce fatty polyethers: okadaic
      acid and its derivatives, the dinophysistoxins, which accumulate in shellfish and
      can cause diarrhetic shellfish poisoning (DSP) when ingested. In freshwater, the
      toxins are microcystins and nodularin, 7 or 5 amino acid cyclic peptides and are
      hepatotoxic. These toxins have caused massive poisoning of wild animals or
      domestic livestock and now are a health threat for humans through use of drinking
      and recreation water. Moreover, all these toxins are potent tumor promoters but
      belong to a new class, different from the TPA class, because they do not act on
      Protein Kinase C. Although the mutagenicity Ames test responds negatively,
      several results show their genotoxic potential, and therefore they are a health
      hazard through chronic exposition to low doses. Finally, okadaic acid, through
      its easy penetration in all cellular types can be used as a tool to study
      mechanisms involved in protein phosphorylation/dephosphorylation processes.

PMID- 9759381
TI  - [Mechanism of action of neurotoxins acting on the inactivation of voltage-gated
      sodium channels].
AB  - This review focuses on the mechanism(s) of action of neurotoxins acting on the
      inactivation of voltage-gated Na channels. Na channels are transmembrane proteins
      which are fundamental for cellular communication. These proteins form pores in
      the plasma membrane allowing passive ionic movements to occur. Their opening and
      closing are controlled by gating systems which depend on both membrane potential
      and time. Na channels have three functional properties, mainly studied using
      electrophysiological and biochemical techniques, to ensure their role in the
      generation and propagation of action potentials: 1) a highly selectivity for Na
      ions, 2) a rapid opening ("activation"), responsible for the depolarizing phase
      of the action potential, and 3) a late closing ("inactivation") involved in the
      repolarizing phase of the action potential. As an essential protein for membrane
      excitability, the Na channel is the specific target of a number of vegetal and
      animal toxins which, by binding to the channel, alter its activity by affecting
      one or more of its properties. At least six toxin receptor sites have been
      identified on the neuronal Na channel on the basis of binding studies. However,
      only toxins interacting with four of these sites (sites 2, 3, 5 et 6) produce
      alterations of channel inactivation. The maximal percentage of Na channels
      modified by the binding of neurotoxins to sites 2 (batrachotoxin and some
      alkaloids), 3 (alpha-scorpion and sea anemone toxins), 5 (brevetoxins and
      ciguatoxins) et 6 (delta-conotoxins) is different according to the site
      considered. However, in all cases, these channels do not inactivate. Moreover, Na
      channels modified by toxins which bind to sites 2, 5 and 6 activate at membrane
      potentials more negative than do unmodified channels. The physiological
      consequences of Na channel modifications, induced by the binding of neurotoxins
      to sites 2, 3, 5 and 6, are (i) an inhibition of cellular excitability due to an
      important membrane depolarization (site 2), (ii) a decrease of cellular
      excitability due to an important increase in the action potential duration (site
      3) and (iii) an increase in cellular excitability which results in spontaneous
      and repetitive firing of action potentials (sites 5 and 6). The biochemical and
      electrophysiological studies performed with these toxins, as well as the
      determination of their molecular structure, have given basic information on the
      function and structure of the Na channel protein. Therefore, various models
      representing the different states of Na channels have been proposed to account
      for the neurotoxin-induced modifications of Na inactivation. Moreover, the
      localization of receptor binding sites 2, 3, 5 et 6 for these toxins on the
      neuronal Na channel has been deduced and the molecular identification of the
      recognition site(s) for some of them has been established on the alpha sub-unit
      forming the Na channel protein.

PMID- 9759382
TI  - [Anthrax toxins].
AB  - Bacillus anthracis, a Gram positive bacterium, is the causative agent of anthrax.
      This organism is capsulogen and toxinogenic. It secretes two toxins which are
      composed of three proteins: the protective antigen (PA), the lethal factor (LF)
      and the edema factor (EF). The lethal toxin (PA + LF) provokes a subite death in
      animals, the edema toxin (PA + EF) induces edema. The edema and the lethal
      factors are internalised into the target cells via the protective antigen. EF and
      LF exert an adenylate cyclase and a metalloprotease activity respectively. The
      structure-function relationship of these three proteins were defined using in
      vitro and in vivo approaches.

PMID- 9759383
TI  - [Scorpion toxins and defensins].
AB  - The scorpion venoms possess many neurotoxic peptides which constitute a group of
      molecular families with a common architecture and a high degree of polymorphism.
      This architecture is found also in circulating antimicrobial peptides belonging
      to the defensins family, which are especially structurally related to the
      blocking potassium channels neurotoxins. The diversification in functions with a
      unique architectural scheme is discussed taking in account the biophysiological
      characteristics of the scorpion order.

PMID- 9759384
TI  - [Anti-insect scorpion toxins: historical account, activities and prospects].
AB  - Some toxins from scorpion venoms, much more toxic to insects than to other animal
      classes, possess high affinity to Na+ channels. These anti-insect scorpion toxins
      have been divided into: 1) alpha toxins which lack strict selectivity for
      insects, do not compete with following groups of anti-insect toxins, resemble
      other alpha scorpion toxins by their structure and their ability, as alpha
      anemone toxins, to prolong insect axonal action potential durations through a
      drastic slowing down of the Na+ current inactivation, 2) excitatory insect
      selective scorpion toxins which induce in blowfly larvae an immediate fast
      paralysis; in isolated cockroach axons, they depolarize and induce a sustained
      repetitive activity of short (normal) action potentials through a shift of Na+
      activation mechanism towards more negative potentials and some decrease of
      inactivation at these potential values, 3) depressant insect selective
      neurotoxins which cause a slow progressive flaccid paralysis of larvae,
      depolarize insect axons and reduce or even suppress evoked action potentials;
      resting depolarizations which are antagonized by a post-application of TTX, are
      due to the opening of sodium channels at very negative potential values and to
      the suppression of their inactivation mechanism. The decrease of the maximal Na+
      conductance following flaccid toxin action may be understood if toxin-modified
      channels opened at very negative potentials values remain open (or re-open) for
      much longer times than in control conditions and pass by substate less conductant
      states. Anti-insect scorpion toxins become of major interest into insect
      neurophysiology and also into insect pest control, due to their specific target
      sites and to the recent constructions of insecticidal baculovirus expressions of
      several of these toxins.

PMID- 9759385
TI  - [Implications of bacterial protein toxins in infectious and food-borne diseases].
AB  - Among the 315 protein toxins elicited by gram positive and gram negative bacteria
      so far characterized, about 50 toxins are currently considered as totally or
      partially, responsible of the pathological manifestations and/or lethality
      resulting from host infection or intoxication (contaminated food) by relevant
      toxinogenic bacteria. A certain number of criteria are required for the
      assessment of indisputable involvement of a toxin or an array of toxins (from the
      same bacteria) in infectious diseases: 1) The bacterial microorganism clearly
      identified as the pathogenic agent of the disease produces component(s)
      considered as toxin(s); 2) The administration to appropriate animal(s) of the
      toxin(s) separated from the relevant bacteria or produced by genetic engineering
      from a heterologous tox+ recombinant bacterial strain produces symptoms and
      pathophysiological disorders that mimic those observed in the natural disease or
      at least those elicited in experimental animals by the cognate toxin-producing
      bacteria; 3) The in vitro incubation of the isolated toxin(s) with appropriate
      animal organs, tissues or cells elicits certain pathophysiological, biochemical
      or metabolic manifestions observed in the host infected with the relevant
      toxinogenic bacteria; 4) Toxin concentration in the organism of the host infected
      by the toxinogenic bacteria should be compatible with the characteristics of the
      relevant disease. The toxins of pathogenic interest exhibit a variety of effects
      in bacterial diseases. Bacteria that colonize a wound or mucosal surface but do
      not invade target cells can produce toxins that act locally or enter the
      bloodstream and attack internal organs (e.g. Corynebacterium diphtheriae, Vibrio
      cholerae, ...). Bacteria growing in a wound can produce toxins that destroy host
      tissue and kill phagocytes in the immediate vicinity of the bacteria, thus
      facilitating bacterial growth and spread. On the basis of the above mentioned
      criteria, the following bacterial diseases among many others are toxin-associated
      (toxinoses): diphtheria, tetanus, botulism, whooping cough, diarrhea, bloody
      diarrhea, hemolytic uremic syndrome, cholera, scarlet fever, toxic shock
      syndrome, gas gangrene, B. fragilis diarrhea, anthrax, pseudomembranous colitis.

PMID- 9759387
TI  - [The role of peptidic toxins in the pharmacological approach of the diversity of
      calcium channels].
AB  - Peptidic toxins extracted from spider, marine snails or snakes venoms, have
      considerably helped the pharmacological characterization of calcium channels.
      They have successfully been used for calcium channels mapping. However, the
      actual situation remains unclear. Genetic investigations demonstrated the
      existence of a great number of types or sub-types of calcium channels. In recent
      year a large number of toxins have been purified. Many of these toxins have
      specific actions on calcium channels and have been used as powerful tools in
      pharmacological approaches of calcium channels. However the pharmacology of the
      calcium channels remains very limited, many of them are waiting for the discovery
      of pharmacological tools allowing their molecular approach in order to
      determinate their biological implications. In this paper we describe the
      different families of calcium channels and toxins that interact with these
      channels. We also recapitulate the "non defined" calcium channels i.e. calcium
      channel which does not correspond to a N, L, P/Q, R or T type channel and for
      which no effector are available. We report the discovery and characterization of
      mapacalcine, a toxin extracted for a marine sponge, as an example of an approach
      of an undefined calcium channels first characterized by electrophysiological
      techniques and for which a specific toxin has been purified allowing its
      pharmacological approach. We also state the possible role of calcium channel
      toxins in the domain of therapeutic applications.

PMID- 9759386
TI  - [Pharmacological properties of fish venoms].
AB  - Fish venoms can be lethal for Vertebrates. The effect depends of dose and
      subject, more than incriminated fish. The most constant symptom is a violent
      pain; but the serious pharmacological effects are respiratory and heart failure
      with marked hypotension and cardiac perturbations, neurologic damage, such as
      seizure and coma. Experimentation is difficult due to venom instability. Activity
      is lost by distilled water, lyophilisation in buffers, several successive
      freezing and defreezing. In addition, when venom is broken, other pharmacological
      effects are evidenced, for instance, with Synanceia verrucosa venom, hypertensive
      phase takes the place of hypotension. It is difficult to distinguish toxin effect
      from this of denaturation products of the toxin. Noradrenaline is present in
      Synanceia venom, and it seems that acetylcholine exists in some venom, at least
      when diluted in saline solution. Other biological active products are present.
      Purified toxins allow pharmacological investigations. Stonefish venom is better
      studied, because venomous glands contain relatively high venom quantity.
      Stonustoxin from Synanceia horrida exerts its action through NO-synthase
      liberation, and its primary action can be attributed to its potent vasorelaxant
      activity, causing a rapid, marked and irreversible hypotension. Trachynilysin,
      from Synanceia trachynis, causes massive release and depletion of acetylcholine
      and damage to nerve and muscle fibres, which can account for the inhibition of
      neuromuscular function, and skeletal paralysis. But the used doses are not
      compatible with respiratory arrest. Verrucotoxin from Synanceia verrucosa
      activates potassium channels dependent from ATP; this can explain damage, and
      probably neurologic and respiratory distress.

PMID- 9759388
TI  - [A new photocoagulation technic for severe non-proliferative diabetic
      retinopathy. A prospective study apropos of 54 cases].
AB  - PURPOSE: This work deals with the photocoagulation treatment of severe NPDR,
      suggesting a new therapeutic practice. It is proposed to adopt treatment
      intensity to each clinical form, to preserve healthy territories through
      biomicroscopy and to evaluate the risk of complications inherent in this
      technique, and to be at least as efficient as comparative studies. MATERIAL AND
      METHOD: We treated 52 eyes and kept under observation 2 eyes which revealed
      severe NPDR. The patients were followed between 1991 and 1996. The approach was
      essentially biomicroscopic. Photocoagulation treatment utilized green, yellow or
      orange wavelengths through panoramic contact lenses. RESULTS: After an average
      follow-up of 30 months, there was a decrease of visual acuity of 0.72 to 0.64
      (Monoyer scale); a severe visual loss in 1.8% of the cases; and an early decrease
      in visual acuity at 6 weeks in 7.4% of the cases. A "High Risk" PDR occurred in
      3.7% of the cases and we had to perform a vitrectomy (1.85% of the cases). We
      treated with less than 1600 I in 68.5% of the cases and with more than 1600 I in
      31.5% of the cases. Patients had 5.5 photocoagulation sessions and were examined
      every 3.5 months on average. CONCLUSION: We believe our therapeutic approach is
      interesting, by comparison with other studies, but that it can be improved. All
      patients show a primary condition in the nasal field which, if treated too
      massively, becomes unable to see and disturbs daily life. We also note the severe
      potential for progression in insulin-dependent patients.

PMID- 9759389
TI  - [A comparative study of thio-tepa and mitomycin C in the treatment of pterygium.
      Preliminary results].
AB  - AIMS: To compare the efficacy of Thio-tepa and Mitomycine C to obviate
      recurrence; to compare cost-efficacy ratios; to evaluate their facility of use
      and their complications. METHODS: In a prospective blinded study, 36 patients
      undergoing surgery for 46 primary and recurrent pterygium were assigned randomly
      to three groups: group 1 received 0.02 mg/ml of Mitomycine C three times daily
      for 5 days; group 2 received Thio-tepa four times daily for 6 weeks, group 3
      served as a control receiving distilled water three times daily for five days.
      RESULTS: Recurrence rates were 38%, in group 1; 28% in group 2; 82% in group 3
      respectively. Follow-up ranged from 15 to 44 weeks (mean 27.93 +/- 8.9 weeks).
      Mean delay recurrence time was 6.3 weeks. Topical Mitomycin caused: iritis,
      conjunctival irritation, excessive lacrymation, photophobia, ocular pain; Thio
      tepa caused: photophobia, foreign body sensation, headache. CONCLUSIONS:
      Mitomycine C appears to be an effective and safe adjunctive treatment for this
      cost-efficacy and this facility of use comparison.

PMID- 9759390
TI  - [Culture of human keratocytes. Influence of culture conditions and
      ultrastructural aspects].
AB  - BACKGROUND: To investigate the influence of fetal calf serum (FCS) and fibroblast
      growth factor (FGF) on human keratocyte growth in vitro and cell differentiation,
      and to describe cultured human keratocyte ultra-structure. METHODS: Human
      keratocytes were cultured in TC 199/Ham F12 media, supplemented or not with 10%
      FCS, aFGF, and bFGF. Keratocyte growth was studied. Cultured keratocytes were
      analyzed by means of immunochemistry and transmission electron microscopy.
      RESULTS: Without fetal calf serum, cell population doubling occurred after 7 days
      of culture and no alpha smooth muscle-actin cell expression was observed. With
      serum, cell population increased by 1 log after 7 days of culture and all of the
      cells were alpha SM-actin + bFGF or aFGF-addition to the serum-containing medium
      resulted in a dramatic decrease in this alpha SM-actin expression. Nuclei were
      found to be oval and regular in cross-sections, and round and indented in frontal
      sections. Numerous cytoplasmic organelles were observed, as were cell expansions,
      gap junctions, omega-shaped structures, and fenestrations. Cultured keratocytes
      synthesized collagen fibers and filaments. CONCLUSION: Fetal calf serum allows
      human keratocytes to grow with a myofibroblast cell phenotype, whereas addition
      of FGF results in a fibroblast cell phenotype. Ultrastructure of cultured
      keratocyte is similar to that observed in situ.

PMID- 9759391
TI  - [Therapeutic and prognostic problems of traumatic cataracts. Apropos of 45
      cases].
AB  - PURPOSE: The purpose of this study was to investigate clinical profile, prognosis
      and therapeutics problems of traumatic cataract. MATERIAL AND METHODS: A
      retrospective study was conducted in 45 cases of traumatic cataracts (1993-1996).
      Mean age was 19 years, principally male. We chose the extracapsular extraction
      with implantation in 28 cases. RESULTS: Overall results were satisfactory (62%
      with VA > 2/10); they are better in patients with implantation and poorer in
      infants. Postoperatively, most complications were major inflammatory and
      secondary capsular opacification essentially children. The importance of systemic
      corticotherapy and prevention of amblyopia in children is emphasized.

PMID- 9759392
TI  - [Visual prognosis factors in congenital cataract].
AB  - PURPOSE: Study of different factors which can change the visual prognosis in
      congenital cataract. METHODS: One hundred seventy eyes of 100 children with
      congenital cataract are operated by extracapsular cataract extraction with limbic
      incision. Posterior rhexis and anterior vitrectomy were associated in children
      under 2 years. Implantation was used in 42%, contact lens in 8%. Other cases were
      corrected by glasses. The prognostic factors studied were: uni- or bilaterality,
      partial or complete aspect of cataract, age of apparition and management, and
      association with other malformations. RESULTS: Only 9 eyes out of 30 with
      unilateral congenital cataracts had visual acuity > or = 2/10; 44.4% of bilateral
      cataracts had visual acuity > or = 2/10; The best visual acuity was noted in
      progressive and partial cataract without associated malformations.

PMID- 9759393
TI  - [Bilateral ischemic optic neuropathy secondary to acute ergotism].
AB  - We report a case of a 31 year-old man who presented a bilateral ischemic optic
      neuropathy associated with headaches and severe systemic hypertension. This
      episode appeared after administration of ergotamine tartrate and macrolides. This
      medication probably led to a vasospasm which occurs in patients with
      hypertension. The cardiovascular and serum lipid evaluations were normal. A
      migraine optic neuropathy can be evoked.

PMID- 9759394
TI  - [Episcleritis and brucellosis. Apropos of a case].
AB  - A 35-year-old man presented a case of recurrent episcleritis revealing
      brucellosis. No concurrent diagnosis other than brucellosis could account for the
      episcleritis. Moreover his status was dramatically improved by specific
      antibiotherapy. A review of the literature showed that uveitis and optic
      neuropathies are the most common ocular manifestations of brucellosis. To the
      best of our knowledge, this is the first case of episcleritis associated with
      brucellosis.

PMID- 9759395
TI  - [Choroid melanoma associated with 2 other primary malignant lesions. Apropos of a
      case].
AB  - A case of choroidal melanoma associated to two other primitive malignancies is
      reported. The patient, a 65-year-old woman had an amelanotic choroidal tumor of
      her left eye. In her clinical history was found a previously treated kidney
      carcinoma eight years ago. A choroidal metastasis was therefore diagnosed. After
      radiation therapy, an initial regression was observed. Fifteen months later, the
      tumor grew again. Enucleation was performed, and histopathology concluded on
      choroidal malignant melanoma. Three years later, a mammal carcinoma was
      discovered and treated by mammectomy. Her ophthalmologic and general status
      remained normal until now. Amelanotic choroidal tumors are difficult to diagnose.
      Regular follow-up can lead to a change in the diagnosis. The occurrence of
      multiple cancers is still not fully understood.

PMID- 9759397
TI  - [Acute open-angle glaucoma in a woman with AS hemoglobinopathy].
AB  - A 64-year-old black woman presented unilateral acute ocular hypertension.
      Gonioscopy showed a blood clot obstructing Schlemm's canal. Intraocular pressure
      returned to normal values after resorption of the blood clot. Hemoglobin
      electrophoresis found a sickle-cell trait, raising the hypothesis that the
      obstruction of outflow was probably due to the mechanism of sickling.

PMID- 9759396
TI  - [Papillary edema and the POEMS syndrome].
AB  - POEMS syndrome is a multisystem disorder associated with plasma cell dyscrasia.
      Papilloedema is a feature of this syndrome with an incidence ranging from 33% to
      84% in published reports. Its pathogenesis remains unclear. We present an
      observation that clearly demonstrates the difficulties to diagnose this
      affection. POEMS syndrome can be accepted as one of the various etiologies of
      papilloedema. Considering this observation and the recent publications, different
      pathological hypothesis are reviewed.

PMID- 9759399
TI  - [Isolated and primary palpebro-conjunctival amylosis. Apropos of 2 cases].
AB  - Ocular amyloidosis a an uncommon condition and conjunctival involvement rarely
      occurs, representing 15% of all ocular localizations. Clinical manifestations
      show a polymorphism requiring a histological diagnosis. Based on two cases of
      primary isolated conjunctivo-palpebral amyloidosis, we discuss the different
      ocular sites. The first case involved false ptosis, a conjunctival infiltration
      and a lower eyelid tumefaction; all located in the left eye. The second case had
      ptosis, a right lower eyelid tumefaction with ectropion and esthetic damage.
      Amyloidosis was confirmed at histologic examination of the conjunctival mucous
      after a special congo red coloration. In order to affirm the isolated
      conjunctival localization, it is necessary to eliminate another amyloidis site.
      The treatment was surgical with excision and cure of ptosis. Ocular amyloidosis
      is a rare condition with polymorphism manifestations. Confirmation is
      histological. The greatest difficulty is management due to disease recurrence.

PMID- 9759398
TI  - [Surgical treatment of retrofoveal choroid neovascularization in multifocal
      choroiditis].
AB  - BACKGROUND: Surgical removal of subfoveal choroidal neovascularization allows
      visual improvement, especially in young patients. METHODS: Three eyes of 3
      patients were prospectively studied. Subfoveal choroidal neovascularization was
      related to presumed ocular histoplasmosis syndrome. The surgical procedure
      included vitrectomy, surgical excision of the neovascular membrane, and air
      tamponnade. RESULTS: Follow-up was 6, 12 and 20 months. Vision improved in 2
      eyes. In one case, recurrent extrafoveal neovascularization was treated with
      laser photocoagulation. DISCUSSION: Surgery seems to be an alternative to
      photocoagulation in subfoveal choroidal neovascularization in presumed ocular
      histoplasmosis.

PMID- 9759400
TI  - [Biocompatibility of a porous alumina orbital implant. Preliminary results of an
      animal experiment].
AB  - PURPOSE: Evaluation of clinical tolerance and scanning electron microscopy study
      of the bio-colonisation of a porous ceramical alumina implant after evisceration
      of the rabbit. Preliminary results. METHODS: Sixteen white New Zealand rabbits
      were eviscerated. A porous hydroxyde alumina ball was implanted in the opened
      sclera and explanted 15, 30, and 90 days after implantation. Clinical tolerance
      was assessed and implant tissular ingrowth was analyzed by scanning electron
      microscopy. RESULTS: One infection was observed and there was no conjunctival
      breakdown. Fibrovascular ingrowth occurred as soon as 15 days after implantation,
      and was full at one month. CONCLUSION: Porous alumina implant orbital tissue
      tolerance and fast fibrovascular ingrowth in the rabbit socket suggest promising
      result in the human anophthalmic socket.

PMID- 9759401
TI  - [Surgery of intravitreous nuclear luxations post-phacoemulsification].
AB  - PURPOSE: To evaluate anatomical and functional results after surgery of retained
      nucleus or nuclear lens fragments into the vitreous cavity after
      phacoemulsification. METHODS: Files of 46 patients that underwent vitrectomy for
      posterior retained nuclear fragments between July 92 and June 96 were studied
      retrospectively. Minimum follow-up was 6 months. Patients having only cortical
      material were excluded. In 34 cases the nucleus or nuclear fragments were removed
      posteriorly during a pars plana vitrectomy using either fragmentation with
      fragmatome (13 cases) or cutting with the vitreotome tip (21 cases). Anterior
      removal after pars plana vitrectomy was performed in 12 cases. 20 patients were
      operated on the first week, 12 during the second week and 14 after the second
      week following phacoemulsification. RESULTS: Forty-one per cent of the patients
      reached 20/40 or better. 28% had less than 20/200. 8 (17%) patients presented a
      retinal detachment, 6 a cystoid macular edema, 6 a bullous dystrophy, and 9 an
      elevated intraocular pressure. At the end of follow-up 89% have been implanted
      (50% had been implanted at the end of the cataract surgery). We found no
      correlation between visual acuity and timing of surgery, anterior or posterior
      site removal of nuclear fragments or lens implantation during
      phacoemulsification. CONCLUSION: Dislocation of the nucleus into the vitreous
      cavity is a serious event during phacoemulsification because of its inflammatory
      and retinal complications. Vitreoretinal surgery allows good visual recovery in
      about half of the patients. Technical handling depends primarily on the nucleus
      density. An IOL may be placed at the end of phacoemulsification if the nucleus is
      not too hard and if the anterior segment has been cleaned carefully.

PMID- 9759402
TI  - [Juvenile glaucoma. Seven case reports].
AB  - BACKGROUND: Juvenile glaucoma is an uncommon form of chronic open angle glaucoma
      that appears between 3 and 35 years of age. METHODS: We report in this study
      seven cases of juvenile glaucoma that occurred in patients melanoderma. RESULTS:
      Three of them had unilateral blindness and in two others visual acuity was
      reduced to light perception in one eye. The intraocular pressure is above to 30
      mmHg in 64.3% of the cases and a myopia was frequently associated. CONCLUSION:
      The insidious development of this pathology and the difficulty of its diagnosis
      among children often result in severe clinical manifestations with high visual
      field defects and optic disc cuppings particularly in melanoderma patients.
      Recent studies have proved autosomal dominant transmission with variable
      penetrance for one kind of juvenile glaucoma and location of the defective gene
      on chromosome 1q.

PMID- 9759403
TI  - [Rapid Tendency Oriented Perimeter (TOP) with the Octopus visual field analyzer].
AB  - PURPOSE: To study the capabilities of a new perimetric strategy with the Octopus
      visual field analyzer: the Tendency Oriented Perimetry. METHODS: Tendency
      oriented perimetry (TOP) attempts to assess the visual field by using answers to
      questions to establish thresholds in the neighboring area. We evaluated 79 visual
      fields with the Octopus strategy using the program 32 and the TOP strategy split
      into the following groups: normal visual field or glaucoma suspects (52),
      moderately advanced glaucoma (16), advanced glaucoma (11). The following
      parameters were analyzed for the two strategies studied: examination time, MS
      (means sensitivity), MD (mean defect), LV (Loss Variance), short term fluctuation
      (RF) and the number of points with a deficit with different p values: p < 0.5; p
      < 1; p < 2; p < 5. RESULTS: TOP perimetry showed a significant reduction of
      exploration time: 11.87 minutes with the Octopus 32 vs 2.49 minutes with the TOP
      strategy (p < 0.001). There is no significant modification for the other
      parameters (MD, MS, RF) except for the LV (Loss Variance) for the global analysis
      and for each separate group. CONCLUSION: The TOP strategy reduces examination
      time significantly but seems to be less accurate especially for the calculation
      of the depth of each scotoma in comparison with the standard Octopus 32
      perimetry.

PMID- 9759404
TI  - [Indocyanine green angiography of basal laminar drusen in the retinal pigment
      epithelium associated with vitelliform macular degeneration].
AB  - PURPOSE: In the mid-late life, basal laminar drusen can be associated with
      vitelliform macular degeneration and choroidal neovascularization. The
      differential diagnosis between these two clinical entities is not always easy
      with fluorescein angiography. The aim of this case report is to describe the
      indocyanine green angiographic features of basal laminar drusen and pseudo
      vitelliform material and to evaluate the role of ICG angiography in
      differentiating new choroidal vessels from vitelliform macular degeneration.
      PATIENTS AND METHODS: Six patients (12 eyes) with central visual loss and
      metamorphopsia underwent a biomicroscopic examination. Diagnosis was basal
      laminar drusen and bilateral vitelliform macular degeneration. Fluorescein and
      indocyanine green angiographies were performed and the results were compared.
      RESULTS: In all eyes, basal laminar drusen were hyperfluorescent with both
      angiographies. On fluorescein angiography, the macular material was
      hypofluorescent early, but gradual staining occurred from the borders in the late
      phase. In 8 out of the 12 eyes, fluorescein angiographic characteristics of the
      macular lesions could not provide clues to differential diagnostic between new
      choroidal vessels and vitelliform material. On indocyanine green angiography, in
      8 eyes the material remained intensely hypofluorescent during the whole sequence.
      In 4 eyes, indocyanine green angiography allowed the identification of
      hyperfluorescent well-defined new choroidal vessels. CONCLUSIONS: Indocyanine
      green angiography allows the visualization of basal laminar drusen and can easily
      differentiate choroidal neovascularization from acquired vitelliform
      degeneration.

PMID- 9759405
TI  - [Intra-corneal rings for the correction of weak myopias].
AB  - OBJECTIVES OF THE STUDY: Intra-stromal rings (ICR) represent a new method for low
      myopic correction. An indirect central flattening is induced by a peripheral
      steepening related to the segments. This surgery was recently approved in Europe,
      but is still under evaluation in the multicenter study controlled by the FDA
      (Food and Drug Administration). We took part in that protocol and report our
      results at one year follow-up. MATERIAL AND METHOD: Twenty-five patients were
      included in the study with 47 operated eyes and a follow-up between 3 to 18
      months. Data relative to refractive results, quality of the vision and anatomic
      changes induced by intrastromal segments will be collected at the issue of a
      rigorous survey. RESULTS: At one year, non-corrected visual acuity was 20/40 or
      better in 100% and 20/20 in 60%. We noted no loss in best visual acuity and an
      improvement of one or two lines in 20% of operated eyes. No significative changes
      were observed concerning: intraocular pressure, corneal sensitivity, central
      pachymetry or corneal endothelium. Three eyes had to be explanted and recovered
      the preoperative refraction. No severe complications were observed. DISCUSSION:
      Analysis of results is in favor of the efficacy, predictability and
      reproductibility of the surgery, which might be better with rings of a diameter
      under 0.40 mm. Occurrence of postoperative astigmatism appears to constitute the
      main limit suggesting discussion on etiologic factors and modalities of
      treatment. CONCLUSION: This concept of intra-corneal rings appears particularly
      promising for correction of low myopia and maybe in the near future for
      correction of others ametropia, requiring design of new specific segments.
      Essential interest of this surgery is the respect of the central area and its
      potential reversibility.

PMID- 9759406
TI  - [Value of lacrymal IgE determination and conjunctival cytology in the diagnosis
      of chronic conjunctivitis].
AB  - PURPOSE: Chronic conjunctival inflammatory diseases may depend upon various
      strongly intricated mechanisms. Discriminating allergy from nonspecific
      inflammation has become of striking importance for diagnosis and treatment. We
      investigated conjunctival inflammatory response by comparing two objective
      biological tools, tear IgE detection and HLA DR expression by conjunctival
      epithelium, as indirect indicators of activation of the Th1 and Th2 subsets,
      respectively. METHODS: Sixty-eight patients (135 eyes) with chronic
      conjunctivitis underwent tear IgE dosage by an ELISA technique and quantification
      of HLA DR expression in impression cytology specimens. 34 had direct or indirect
      clinical indications of allergic mechanisms, 22 had chronic conjunctivitis
      without any sign of allergy, and 12 suffered from isolated nonallergic dry eyes.
      RESULTS: Patients clinically considered as allergic only showed positive IgE in
      31 out pf 68 eyes (46 per cent), whereas 11/44 (25%) and 7/24 (29%) eyes with
      nonspecific conjunctivitis and dry eyes respectively were also positive. HLA DR
      positivity in epithelial cells was found in 18/61 (29.5%), 15/40 (37.5%) and 9/22
      (41%) eyes, respectively. HLA DR expression by epithelial cells was negatively
      correlated with tear IgE, as most specimens positive to one criterion were
      negative to the other one (37 eyes DR+ IgE-, 35 eyes DR- IgE+, and 5 eyes DR+
      IgE+; chi-square: p = 0.0001). CONCLUSION: As IgE synthesis and HLA DR induction
      may represent indirect indicators of the activation of the Th1 and Th2 subsets,
      association of these two simple tests could be interesting for the routine
      assessment of the mechanisms of inflammatory ocular surface diseases.

PMID- 9759407
TI  - [Choroidal metastases of a bronchial carcinoid tumor. Review of cases in the
      literature. A case report].
AB  - Carcinoid tumors are rare tumors with low malignancy. They are most often located
      in the digestive system and the bronchial tree. They metastasize to the lymph
      nodes, liver, bones and very rarely to the eye. Choroidal metastases almost
      always originate from the bronchial tree. Inversely, most orbital metastases
      originate in the digestive tract. Sometimes they have an orange color useful for
      diagnosis. We report the case of a woman who developed a bronchogenic carcinoid
      tumor at the age of 18, and presented five years later with bilateral and
      multifocal choroidal metastases. There was no other metastatic site. She has been
      treated with photocoagulation and cryotherapy. From the 25 previously reported
      cases, one can summarize that these specific metastasis grow slowly and allow
      good long-term survival.

PMID- 9759408
TI  - [Ocular trauma and caustic burns by air bags].
AB  - We report two cases of ocular injuries caused by airbag inflation. These cases
      illustrate two main types of airbag-induced eye injuries: chemical and traumatic.
      In the first case, chemical keratitis was caused by the aerosol spray of alkaline
      particles produced by the airbag deployment system. In the second case, the high
      speed deployment system caused mechanical injury to the anterior and posterior
      segments demonstrating the effect of the sudden deceleration when the individual
      hits the airbag. These two cases as well as others reported in the literature
      suggest that ocular injury should always be suspected because of the inherent
      traumatic effect of the airbag protection system.

PMID- 9759409
TI  - [Unilateral retinoblastomas with late bilateralization. Three case reports].
AB  - Three cases of unilateral retinoblastoma with late bilateralization are presented
      in this study. The rare occurrence of this event underlines the need for
      prolonged follow-up in the fellow-eye, even in the absence of familial
      retinoblastoma. In these three cases, the first affected eye was enucleated after
      a diagnosis made at three months, sixteen months and three years of age. New
      tumors appeared in the second eye when the children were sixteen years old in one
      case and five years old in two cases.

PMID- 9759410
TI  - [Capsular bag distension syndrome after capsulorhexis].
AB  - We present one case of capsular bag distension associated with lens
      phacoemulsification, capsulorhexis and posterior chamber intraocular lens (IOL)
      insertion. Capsular bag distension is a rare postoperative complication of
      continuous tear anterior capsulotomy and presents the following characteristics:
      (1) postoperative myopic over-refraction; (2) shallowing of the anterior chamber
      associated with anterior shift of the IOL and the iris diaphragm; (3) important
      posterior distension of the posterior capsule and (4) sealing of the capsule to
      the anterior surface of the IOL. In our case, recovery of vision was incomplete
      after cataract surgery although the procedure was uneventful and no other ocular
      pathology was found. A neodymium: YAG laser anterior capsulotomy peripheral to
      the edge of the IOL remedied the situation allowing the capsular fluid to regress
      into the anterior chamber and the IOL to return in a normal posterior position.

PMID- 9759411
TI  - [Laser CO2 and ocular plastic surgery].

PMID- 9759412
TI  - [Retinal vein occlusion and lipoprotein (a)].
AB  - PURPOSE: Epidemiological studies have shown a significant correlation between
      increased levels of lipoprotein (a) and coronary and cerebral vascular diseases.
      Lipoprotein (a) presents a striking homology with plasminogen and may therefore
      complete with binding of plasminogen at fibrin and at the endothelial cell
      surface, leading to fibrinolytic system dysfunction. The aim of this work is to
      study the relationship between increased levels of Lp(a) and retinal vein
      occlusion. METHODS: 132 consecutive patients with retinal vein occlusion were
      screened for lipoprotein (a) level. They also underwent initial and final visual
      acuity measurement, fluorescein angiography and blood tests including glucose,
      cholesterol and triglyceride levels, apolipoprotein A1 and B, protein
      electrophoresis, coagulation tests. Lipoprotein (a) results were compared with
      those of 52 age, sex and cardiovascular risk factors-matched controls. RESULTS:
      Lipoprotein (a) values were significantly higher in the retinal vein occlusion
      group than in the control group (p = 0.05). Elevated lipoprotein (a) (> 0.1 g/l)
      levels were observed more often in retinal vein occlusion patients (61%) than in
      the controls (42%; p < 0.02). No correlation was found in retinal vein occlusion
      patients between high levels of lipoprotein (a) and a severe form of retinal vein
      occlusion. Lipoprotein (a) levels were similar in central vein and branch vein
      occlusion patients. CONCLUSION: Lipoprotein (a) has been shown to be correlated
      with cardiovascular disorders and may also be involved in retinal vein occlusion,
      probably by dysfunction of the fibrinolytic system. However, it does not seem to
      be a prognostic factor of retinal vein occlusion and its role has to be
      elucidated in further studies.

PMID- 9759413
TI  - [Clinical features and genetic analysis in a family with X-linked incomplete
      congenital stationary night blindness (CSNBi)].
AB  - PURPOSE: We describe particular clinical features in a three-generation family
      with X-linked CSNBi and present the genetic analysis. METHOD: The diagnosis of
      CSNBi was established on clinical and electrophysiological criteria. Polymorphic
      DNA markers of the Xp region were analyzed by fluorescent polymerase chain
      reaction. RESULTS: Clinical findings evidenced an atypical association of both
      myopia and hyperopia in the same brotherhood. The most interesting feature in
      this family was the observation of major worsening of the clinical shape between
      the first and the third generation of affected individuals. DNA analysis did not
      show significant linkage between the disease and markers of the Xp11-p21 region.
      Southern analysis did not show expansion of trinucleotide repeat CAG/CTG and
      CCG/CGG over the three generation. CONCLUSION: Haplotypic analysis together with
      clinical observations allow to exclude the existence of a myopia gene closely
      linked to the CSNB2 locus. The clinical anticipation observed in this family does
      not seem to be linked with trinucleotide repeat expansion CAG/CTG or CCG/CGG.

PMID- 9759414
TI  - [Intracameral lidocaine and phacoemulsification under topical anesthesia. Apropos
      of 80 operations].
AB  - PURPOSE: To evaluate the advantage of intracameral unpreserved lidocaine for
      patient comfort during phacoemulsification under topical anesthesia. METHODS: In
      this prospective study, we performed 80 phacoemulsifications under topical
      anesthesia, with tetracaine 1% drops, 10 minutes before and at the start of
      surgery: 40 patients received 0.3 cc balanced salt solution (BSS) intracameral
      injection; 40 patients received 0.3 cc unpreserved lidocaine 1% intracameral
      injection. The same surgical procedure was performed in both groups: 3.2 mm
      temporal corneal self-sealing incision, capsulorhexis, foldable polyHEMA IOL
      implantation into the capsular bag. There was no intravenous sedation. RESULTS:
      Forty-eight percent (19) in the BSS group and 70% (28) in the lidocaine group
      felt no pain. 10% (4) in the BSS group reported sharp pain during
      phacoemulsification. During IOL insertion, no pain was reported by 48% (19) in
      the BSS group, and 75% (30) in the lidocaine group; 10% (4) in the BSS group felt
      severe pain (significant difference: p < 0.05). Endothelial cell loss was 6% in
      the BSS group, and 6.4% in the lidocaine group (non significant difference).
      CONCLUSION: Intracameral lidocaine is safe and effective in decreasing discomfort
      among patients undergoing phacoemulsification under topical anesthesia.

PMID- 9759415
TI  - [Evaluation by laser flare meter of the inflammatory response after cataract
      surgery].
AB  - PURPOSE: To prospectively evaluate use of the laser flare meter the inflammatory
      response after phacoemulsification with four different types of intraocular
      lenses. METHODS: Measurements with the Kowa laser flare meter FC-500 were done
      before surgery and at 1, 6 and 21 days following standard phacoemulsification
      with corneal incision in 157 patients. The patients were randomized in four
      groups to receive HSM IOL (group I), foldable acrylic IOL (group II), foldable
      three-piece silicone (group III), and foldable single-piece silicone (group IV).
      RESULTS: Overall, mean flare values were increased at D1, and decreased rapidly
      to normal values at D21. Intragroup analysis showed a slight increase of flare
      value observed in the PMMA group (p = 0.0015) and silicone monobloc group (p =
      0.001) at D21 compared to D0. There was no statistical difference found between
      D0 and D21 in the acrylic and the silicone three pieces groups. At D1, a
      significant increase of flare values was observed in the PMMA (28.9 ph/ms) and
      silicone three pieces (28.8 ph/ms) groups, as compared to silicone monobloc group
      (22 ph/ms). At D21, the acrylic group had a significantly lower mean value than
      PMMA and silicone monobloc groups. No statistical difference was observed between
      acrylic and three-piece silicone at D21. CONCLUSION: This study shows that the
      inflammation in the four groups was very low after phacoemulsification by a
      corneal incision and attempts to explain the impact of the incision length on the
      breakdown of blood-aqueous barrier.

PMID- 9759416
TI  - [Scale for evaluating desirable ametropia or eumetropia].
AB  - GOAL: The purpose of this study is to assess the degree of desirable ametropia in
      cataract surgery. MATERIAL AND METHODS: A scale for evaluation was created. It
      allows to measure the desired distance for a neat uncorrected vision (desired
      ametropia) after cataract surgery that presbyopic patients (monocular vision)
      would like to obtain. This scale helps to calculate the power of the intraocular
      lens to be implanted. The scale was shown to a series of 50 consecutive
      presbyopic patients. Refraction was the same in both eyes. The interest of
      patients in the evaluation of their desirable ametropia was measured on a scale
      from 0 to 5. RESULTS: Interest was good for 50% of patients (grade > or = 3).
      Mean distance desired by patients for a neat uncorrected vision was 1 meter.
      Preoperative myopia and hyperopia have no significantive influence upon the
      distance desired for a neat uncorrected vision. CONCLUSION: The choice of the
      power of the lens implanted during cataract surgery should take into account the
      patients' desires. An evaluation of the postoperative desirable ametropia should
      be systematic.

PMID- 9759417
TI  - [Brown syndrome: current status].
AB  - PURPOSE: Brown's syndrome is a form of anatomical strabismus, or retraction
      syndrome. It is defined by active and passive limitation of upward gaze in
      adduction in the field of action of the inferior oblique muscle. The etiology of
      Brown's syndrome remains unknown. The defect lies at the level of the superior
      oblique's tendonis trajectory via the trochlea. We studied the frequency of
      clinical signs and results after surgery in patients presenting congenital
      Brown's syndrome. PATIENTS AND METHODS: Our study involved 18 children. They all
      underwent complete ophthalmological examination with orthoptic testing, pre and
      postoperatively. RESULTS: Neither sidedness nor predominance of sex was noted.
      Compensatory head posture was noted in 7 of 18 cases. Limitation of upward gaze
      in adduction was a constant finding, with a positive duction test. Eleven cases
      underwent superior oblique recession. Results of surgery were satisfactory, with
      resolution of compensatory head posture in over 80% of cases. CONCLUSION: The
      etiology of congenital Brown's syndrome remains unknown. The different surgical
      techniques give inconstant results. Operative indication is decided only when in
      the presence of well defined clinical manifestations: CHP, deviation in primary
      position with alteration of binocular vision.

PMID- 9759418
TI  - [Panophthalmitis and results of HIV tests. Experience at the Cocody University
      Hospital Center in Abidjan, Ivory Coast].
AB  - PURPOSE: We assessed the frequency of panophthalmitis in HIV-infected patients.
      MATERIALS AND METHODS: Thirty-seven cases of panophthalmitis were screened out of
      420 hospitalized patients of ophthalmology department of Cocody Teaching
      University Hospital, Abidjan, Ivory Coast, from January to October 1995. HIV
      tests were performed in 11 patients. RESULTS: Mean age was 40 years (from 10
      months to 75 years). Four patients (36.4% of tested patients) were infected by
      HIV. Contrary to seronegative patients, panophthalmitis cases in HIV-infected
      patients occurred spontaneously without any apparent exogenous cause (foreign
      bodies). Most of patients were young (from 18 to 47 years old). CONCLUSION: We
      draw the attention of eye specialists of the frequency of panophthalmitis without
      exogenous apparent cause in HIV patients. It would be interesting to perform a
      transvitreal needle biopsy in order to search for intraocular toxoplasmosis that
      should be the first cause.

PMID- 9759419
TI  - [Ultrastructural and immunohistochemical study of 3-dimensional cultures of human
      keratinocytes on a collagen gel].
AB  - PURPOSE: To investigate the ultrastructural and immunochemical features of three
      dimensional cultures of human keratocytes in collagen gel matrix. METHODS: Human
      keratocytes were obtained from primary cultures of stromal explains. They were
      cultured in bovine type I collagen gel matrix for 6 weeks. Keratocyte-populated
      gels were analyzed by means of immunochemistry and transmission electron
      microscopy. RESULTS: Human keratocytes cultured in collagen gel matrix developed
      processes and formed networks of connecting cells. They showed positive staining
      for vimentin, collagen I, V, and VI, and connexin. Electron microscopy showed
      elongated cells with processes and gap junctions. Keratocytes synthesized
      collagen fibrils and filaments. No fibrils' organization similar to that observed
      in the normal human corneal stroma (i.e. parallel bundles of collagen fibrils)
      was observed. CONCLUSION: Ultrastructure and immunochemical phenotype of three
      dimensional cultures of human keratocytes in collagen gel matrix are similar to
      those observed in situ. These cultures represent a useful in vitro model to study
      the different corneal stroma components.

PMID- 9759420
TI  - [Retinoblastoma: importance of genetic counseling].

PMID- 9759421
TI  - [Nummular keratopathy in Crohn's disease. Apropos of a case].
AB  - We report an unusual case of nummular keratopathy of the left eye in a 58-year
      old woman with active Crohn's disease, presenting colo-anal and joint symptoms.
      Spontaneously decreased bowel activity and local steroid treatment provided
      symptom relief and incomplete decrease in volume of subepithelial elevations. We
      discuss the clinical aspects, the epidemiologic factors, the pathogenic
      mechanisms and the treatment of keratopathy in Crohn's disease.

PMID- 9759422
TI  - [What is your diagnosis and treatment? Acute anterior uveitis without hypopyon].

PMID- 9759423
TI  - [What would you do? Borderline ocular hypertension, visual field changes, and
      papillary atrophy in a 65-year-old patient].

PMID- 9759424
TI  - [Relaxing retinopathies and liquid perfluorocarbons].
AB  - PURPOSE: To assess the long term anatomic and functional follow-up of large
      relaxing retinotomies performed with liquid perfluorocarbon in severe
      vitreoretinal proliferation surgery. METHODS: A large relaxing retinotomy (more
      than 90 degrees) was realized in 40 eyes of 39 patients for anterior
      vitreoretinal proliferation (30 rhegmatogen retinal detachments, 8 intraocular
      foreign bodies, 2 ocular traumas). Follow-up was always longer than 6 months.
      Vitreoretinal proliferation secondary to ischemic or inflammatory retinopathy
      were excluded. The liquid perfluorocarbon was perfluorodecalin and was used for
      all eyes, as well as final intraocular tamponade by silicon oil ended every
      intervention. RESULTS: Sixty-seven % of patients had already had a former
      vitrectomy, and 75% a retinal surgery. Mean size retinectomy was 170 degrees.
      Nine patients underwent a new vitreoretinal procedure which included in 7 cases a
      necessary new retinectomy. Silicon oil could be removed in 55%, after a mean
      period of 6, 5 months. Mean time follow-up was 13 months. At the end of follow
      up, 80% of retina were attached. Visual acuity remained low with 25% equal to
      1/20 or more; 45% of eyes increased their acuity, 25% remained stable and 30%
      worsened. Main complications were epimacular proliferation, keratopathy and
      increased intraocular pressure. CONCLUSION: Relaxing retinotomies provide
      satisfying anatomic results and allow a preservation of some visual function. The
      use of liquid perfluorocarbons facilitates their realization. The initial size of
      retinectomy should be sufficient.

PMID- 9759425
TI  - [Anisometropia and presbyopia: prescription of progressive lenses, a new
      approach].
AB  - OBJECTIVE OF THE STUDY: To show that anisometropia does not absolutely preclude
      the prescription of progressive lenses. MATERIALS AND METHODS: Forty-one
      anisometropes and presbyopes were selected for a prolonged trial of visual
      correction using progressive lenses. The congenital or acquired type of their
      anisometropia and its particular form were also studied. Each patient was
      submitted to a protocol comprising of a series of ophthalmologic and orthoptic
      tests so as to evaluate the patient's subjective far and near refraction, with
      measurement of phorias and of horizontal and vertical ductions, visual acuity,
      and the quality of binocular vision while looking in different directions. A
      preliminary trial of correction in actual situation was done in order to check
      fusion in near vision. The entire range of tests was repeated two months after
      the patient was provided with the lenses. The tolerance for progressive lenses
      during the different activities of daily life was evaluated after the second and
      the sixth months. RESULTS: Seven patients presenting an associated strabismus
      were not provided with the lenses because the initial pre-lens trial revealed a
      total inability to read within the near-vision zone. Among the 34 patients
      provided with the lenses, 21 constantly wore their progressive lenses and said
      that they were satisfied, 6 wore their progressive lenses during daily activities
      but preferred to use their unifocal lenses for prolonged reading, and 7 abandoned
      their progressive lenses because they could not tolerate them. Association with a
      strabismus is not synonymous with an initial impossibility or with abandonment
      because of the 27 patients who constantly wore their progressive lenses 9 were
      strabismic. The best results were obtained in the age range of 45 to 52 years
      old, for visual acuity for > 20/40, and in cases of congenital anisometropia with
      intermittent or permanent unilateral neutralization. On the other hand, patients
      presenting an acquired anisometropia, particularly postoperative, proved to be
      poor candidates. CONCLUSION: Weak and strong anisometropia does not absolutely
      preclude the prescription of progressive lenses except for certain strabismic
      subjects with an abnormal lateral-oriented posture.

PMID- 9759426
TI  - [Morphometry of the optic disc in Togolese patients with glaucoma or suspected
      glaucoma. Preliminary study].
AB  - PURPOSE: The aim of this study was to measure morphometric parameters of the
      optic disc in Togolese glaucoma patients and suspects by the mean of the
      millimetric scale of the slit lamp and the Goldmann contact lens. MATERIAL AND
      METHOD: We selected 202 patients (393 eyes) with a mean age of 36.69 years +/-
      15.33 (standard deviation); they were divided into 2 subgroups A (162
      glaucomatous) and B (40 glaucoma suspects); direct reading of the slit lamp
      millimetric scale and the Goldmann contact lens was used. RESULTS: In the group
      A, the optic disc vertical diameter was 1.792 +/- 0.21 mm; the horizontal
      diameter was 1.701 +/- 0.198 mm. In the group B, vertical disc diameter was 1.700
      +/- 0.262 mm; the horizontal one was 1.662 +/- 0.190 mm. The vertical cup disc
      diameter was 1.147 +/- 0.274 mm in the group A and 0.708 mm +/- 0.274 mm in the
      group B. The neuroretinal area was 1.360 +/- 0.524 mm2 in group A and 1.786 +/-
      0.467 mm2 in group B. CONCLUSION: This study using millimetric scale of the slit
      lamp and the three mirrors Goldmann contact lens was easy, simple and useful
      clinically. It could be helpful in conducting quantitative studies in countries
      with low resources because this method is costless compared with others.

PMID- 9759427
TI  - [Long-term results of cobalt 60 curietherapy for uveal melanoma].
AB  - PURPOSE: To analyze 65 patients with uveal melanomas treated with cobalt plaque
      therapy with regards to mortality, visual results and complications. PATIENTS AND
      METHODS: Most of the melanomas were large (T3: 52.5%), with a mean largest
      dimension of the base of 11 mm, and a mean thickness of 6 mm. Most of the tumors
      were located in the choroid (95%), with an anterior margin behind the equator
      (65%), and a posterior margin at less than 3 mm of the disc and/or of the macula
      (69%). The plaque radiotherapy delivered a mean dose of 95 Gy to the tumor apex,
      either with a cobalt plaque alone (51 cases), or in association with a ruthenium
      plaque (14 cases). The mean follow up period was over 8 years. RESULTS: The local
      control was achieved initially in 86% of the eyes. The estimated melanoma
      specific survival rate was 83% after 5 years and 74% after 10 years. The main
      parameter associated with the metastases was the largest dimension of the base (p
      < 0.01). The eye was retained in 83% of the cases. The probability of keeping a
      vision better than or equal to 0,1 was 39% after 5 years and 27% after 10 years.
      The main parameter associated with the visual loss was the tumor size (p < 0.01).
      The complications included cataract (39%), radiation retinopathy (34%), with
      maculopathy (19%) and/or papillopathy (13.5%), vitreous hemorrhages (22%),
      neovascular glaucoma (15%) and retinal detachment (12%). CONCLUSION: These
      results supported the value of cobalt plaque radiotherapy in the management of
      uveal melanomas.

PMID- 9759428
TI  - [Update on a diagnostic test for choroideremia: the protein truncation test
      (PTT)].
AB  - PURPOSE: The aim of this study was to define the RT-PCR-PTT parameters for CHM
      gene analysis and to evaluate its interest as a method for CHM mutation
      screening. METHODS: The entire CHM coding region was reversed-transcribed in
      three overlapping cDNA segments (RT-PCR) which were amplified and further
      analyzed by PTT after in vitro transcription/translation. RESULTS: This strategy
      enabled us to detect a truncated peptide in each of the 6 unrelated patients from
      southern France who were investigated. The mutation was further characterized by
      direct sequencing of the RT-PCR product. CONCLUSION: In CHM gene, all conditions
      are present to make the RT-PCR-PTT strategy the method of choice for mutation
      screening. As a result of the simplified protocol described in this study, the
      families of the patients could benefit from accurate carrier-status assessment.

PMID- 9759429
TI  - [Artificial trabeculum (MESH). Clinical and histological study in the rabbit].
AB  - PURPOSE: Designed to avoid postoperative hypotony that often occurs after
      trabeculectomy and to maintain long lasting filtration, the MESH is a thin porous
      expended polytetrafluoroethylene (ePTFE) implant that mimics the physiological
      meshwork. The aim of this study is to assess the tolerance, biocompatibility and
      effectiveness of this device during 6 months in the rabbit. MATERIAL AND METHODS:
      We used an ePTFE with about 5 microns pore size (Zytex). The head of the implant
      is 3,0 mm wide and 1,5 mm long and fits in the anterior chamber. The tail is 2,0
      mm wide and 3,0 mm long and fits in the subconjunctival space. The MESH is 250
      microns thick. 24 Dutch pigmented rabbits were selected because their dark
      pigmented iris contrasts with the ePTFE implant giving a better visualization.
      All the animals were cared for in accordance with ARVO resolutions. Surgery was
      performed on the right eye by the same surgeon (P.H.), the left eye serving as
      control for IOP measurements. The animals were distributed in 3 groups: one with
      MESH alone (MESH), one with MESH and Mitomycin C (MMC), one with MESH and 5-FU (5
      FU). Follow-up was performed every week (W) during 6 months including IOP
      measurement, slit lamp observation, photography and bleb assessment. Histological
      study was done at POD 0, 15, 30, 90 and 180 one eye in each group. Student t test
      and alternate Welch t test were used for statistics. RESULTS: Filtering bleb: no
      bleb was visible before W3. A bleb was found between W3 and W6, decreasing
      between W6 and W9 with no more change after W10. The MESH implant: no change
      appears in the color of the MESH during the study. Some iris pigments or
      synechiae were seen in some cases. No extrusion occurred. Intraocular pressure:
      IOP was lower than in the control eye. The statistical analysis showed a
      significant lower pressure for the MESH alone at W5 (p = 0.0069), for the 5-FU
      group at W1 (p = 0.0326), W2 (p = 0.0488), W4 (p = 0.0312). With Mitomycine C we
      found very significant results at W1 (p = 0.0073), W2 (p = 0.0136), W4 (p =
      0.0497), W9 and W11 (p = 0.0174). After W12 the groups were joined and IOP was
      significantly decreased at W17 (p = 0.0376) and W23 (p = 0.0462). Histology
      confirmed the correct position of the MESH, its biocompatibility and its ability
      to drain aqueous humor even if there is colonization of the pores by fibroblast
      like cells. CONCLUSION: The present study has shown that the filtering bleb
      appeared after 3 weeks without major hypotony. The material was integrated only
      in the intrascleral tunnel and was stable. After 6 months the Mesh was well
      tolerated. The new concept has a simple surgical technique, less invasive than
      trabeculectomy and required less surgical time. This technique reduced IOP and
      produced long survival blebs in rabbits. This device appears suitable for the
      surgical treatment of open angle glaucoma.

PMID- 9759430
TI  - [Postoperative ptosis: etiopathogenesis, clinical analysis, and therapeutic
      management. Apropos of a series of 43 cases].
AB  - PURPOSE: Acquired postoperative ptosis (PP) are difficult to situate in the
      current classification of ptosis. Assessement of the mechanisms, the clinical
      features and the possible treatments of these PP would suggest a new
      classification of ptosis. MATERIAL AND METHODS: Among 260 cases of surgically
      corrected ptosis, 43 cases of PP (16.5%) were detected and analyzed. RESULTS:
      Forty cases of PP were eligible for this study. Their responsible mechanisms were
      aponeurotic (57.5%), mixed (aponeurotic and/or myogenic and/or neurogenic)
      (27.5%) and myogenic (15%). PP was assessed in most cases as being mild (77.5%)
      and the levator's muscle contraction was most often mildly impaired (77.5%). In
      these cases, surgical procedure was performed: levator aponeurosis disinsertion
      repair (85%), Fasanella-Servat procedure (2.5%), frontalis sling (2.5%) and other
      surgical procedure with synthetic materials (10%). Postoperative complications
      included 1 case of persistent lid edema and 4 cases of spontaneous suture
      rupture. Six patients (15%) were secondarily reoperated: 2 for overcorrection
      (5%) and 4 for undercorrection (10%). The general outcome was good in 90% of
      cases, insufficient in 5% of cases and unsatisfactory in 5% of cases. CONCLUSION:
      This study confirms the previously described features of the PP: onset after
      anterior surgery procedures of usually moderate ptosis, induced by an aponeurotic
      defect mechanism in most cases. The treatment was exclusively surgical: anterior
      reinsertion of the levator aponeurosis. For better management, we suggest a new
      ptosis classification: aponeurotic, myogenic, neurogenic and mixed (aponeurotic
      and/or myogenic and/or neurogenic) and false or pseudo-ptosis.

PMID- 9759431
TI  - [Small retinal, cochlear, and cerebral infarctions in the young patient, "SICRET"
      syndrome of Susac syndrome].
AB  - A 22-year-old-lady presented with multiple occlusions of the branches of the
      central retinal artery, accompanied by neuro-encephalic disorders and deafness.
      This triad is known as SICRET Syndrome (Small Infarction of Cochlear, Retinal and
      Encephalic Tissue). This rare syndrome, as well referred to as Susac syndrome,
      affects only the women and the three tissues mentioned above: eye, ear, brain.
      The course was characterised by a series of partially regressive evolutive steps.
      A remission had been obtained since two years with immuno-supressor and anti
      coagulant therapy. The neuro-encephalic and cochlear disorder regressed in
      contrast to the severe sequel on the right eye.

PMID- 9759432
TI  - [Optic neuromyelitis and bilateral acute retinal necrosis due to varicella zoster
      in a patient with AIDS].
AB  - We report a case of bilateral acute retinal necrosis (ARN) following an acute
      optic neuromyelitis (AONM) in an immunodepressed patient (T CD4 lymphocyte count
      under 50/mm3) suffering from acquired immunodeficiency syndrome (AIDS). Despite
      the medical treatment the evolution led to blindness by bilateral total retinal
      detachment. The neuro-ophthalmological features occurred prior to the retinal
      manifestation, and the acute optic neuromyelitis occurred after a spreading
      zoster. The varicella-zoster virus (VZV) seemed to be involved because of
      recurring cutaneous zoster, spreading of this zoster just before the AONM,
      previous reports showing a link between VZV and AONM, and VZV and ARN. However,
      our patient had first an AONM responding well to corticosteroid therapy following
      one month later by an ARN leading to blindness despite the antiviral treatments
      received as soon as possible. There is a chronical viremia+ in immunodepressed
      patients with recurring and spreading zoster. The rupture of the hemato
      encephalic barrier observed in AONM could facilitate the invasion of the eye by
      the virus, leading to an ARN. This hypothesis could explain the two complications
      due to the VZV, the AONM and the ARN, the first one is of dysimmunitary origin
      and the second one could probably result of a direct viral attack of the retina.
      This should incite to treat as soon as possible each retrobulbar optic neuritis
      in patients with AIDS, especially if past history of zoster.

PMID- 9759433
TI  - [Candida chorioretinitis in drug addicts. Apropos of 2 cases].
AB  - We report two cases of candidal chorioretinitis occurring to two friends who
      abused of intravenous crack using the same syringe . An endophthalmitis "a
      minima" due to a therapeutic delay arose in one patient, when a rare spontaneous
      healing happened to the second patient. In both cases, an epiretinal membrane is
      noted after the lesions scarred. Ocular candidal infection is a typical
      complication occurring to intravenous drug addicts. The visual prognosis depends
      not only on early diagnosis and treatment, but also on a strict follow-up because
      late complications are frequent in spite of the healing of initial lesions.

PMID- 9759434
TI  - [Postoperative choroid detachment following microsurgery for rhegmatogenous
      retinal detachment].
AB  - PURPOSE: To evaluate the incidence, predisposing and prognosis factors of post
      operative choroidal detachment after microsurgery of rhegmatogenous retinal
      detachment. MATERIALS AND METHODS: We conducted a retrospective study on a series
      of 595 consecutive rhegmatogenous retinal detachments referred before any
      previous failed surgery. Univariate statistical analysis of the data was
      conducted with evaluation of the odds ratio. RESULTS: Postoperative choroidal
      detachment developed in 23/595 eyes (3.8%). Significant predictive factors for
      post operative choroidal detachment included patient's age over 50 years, male
      gender, pseudophakia, retinal detachment higher than 90 degrees and giant tears.
      We found no correlation between postoperative choroidal detachment and the
      retinopexy method, subretinal fluid release and the type of scleral buckling
      procedure (segmental versus incercling). Postoperative choroidal detachment did
      not influence at a statistically significant level the postoperative outcome.
      Permanent retinal reattachment was achieved in 20 of the 23 eyes (87%) with
      postoperative choroidal detachment, and 564 of 572 eyes (93%) with no post
      operative choroidal detachment (p > 0.05). Postoperative PVR occurred in 3 of the
      23 eyes (13%) with postoperative choroidal detachment and 3 of the 572 eyes (5%)
      with no postoperative choroidal detachment (p > 0.05). The postoperative visual
      outcome was not influenced by the occurrence of postoperative choroidal
      detachment. CONCLUSION: Postoperative choroidal detachment after retinal
      detachment microsurgery is a rare complication. Its prognosis is good. The
      occurrence of postoperative choroidal detachment does not influence the
      postoperative outcome of retinal detachment microsurgery.

PMID- 9759435
TI  - [Combined phacoemulsificaion/membrane resection and macular edema].
AB  - PURPOSE: To evaluate the occurrence of macular edema (ME) after epiretinal
      membrane resection, managed either with simple vitrectomy or with combined
      vitrectomy and phacoemulsification. MATERIAL AND METHODS: Two groups of 12
      patients had a vitrectomy for epiretinal membrane associated or not to a
      phacoemulsification. A fundus fluorescein angiography was performed pre and
      postoperatively and at least 3 months after the surgery. RESULTS: In the group of
      patients who had a simple vitrectomy, a ME was observed in 50% of the cases
      preoperatively and in 25% of the cases at the end of follow-up. In 3 cases,
      preoperative ME was worsened after the surgery. In the group of patients who were
      treated by a combined vitrectomy and phacoemulsification, a ME was observed in
      25% of the cases preoperatively and in 50% of the cases at the end of follow-up.
      A de novo ME was observed in 3 cases. CONCLUSION: Combined vitrectomy and
      cataract surgery could allow a rapid recovery of visual acuity but might increase
      the occurrence of ME.

PMID- 9759436
TI  - [Rupture of the hemato-ocular barrier, studied by fluorophotometry, in uveal
      melanoma patients. Preliminary results].
AB  - PURPOSE: To evaluate the use of intravenous vitreous fluorophotometry in
      assessment of the blood-aqueous barrier in eyes with uveal melanoma. METHOD:
      Vitreous fluorophotometry was performed before treatment in 14 patients with
      uveal melanoma. Both eyes of patients were examined, and fifteen control healthy
      patients were examined between November 1996 and December 1996 at the department
      of ophthalmology of Bicetre hospital. RESULTS: Tumors with height > 6 mm and
      serous retinal detachments were accompanied by marked alterations of the blood
      aqueous barrier, vitreous fluorophotometry showed diffusion of dye in posterior,
      mid and anterior vitreous: 2.99 ng/ml in the posterior vitreous and 5.20 ng/ml in
      the anterior vitreous. The posterior vitreous fluorescence at 60 minutes in the
      control eyes was 1.43 ng/ml and 1.30 ng/ml in the anterior vitreous. Diffusion of
      dye was present in the posterior vitreous in patients with tumor height less than
      6 mm: 2.38 ng/ml (1.43 ng/ml in control eyes) at 60 minutes. CONCLUSIONS:
      Fluorophotometry provides a method for the assessment of the blood-aqueous ocular
      barrier in eyes with choroidal melanoma.

PMID- 9759437
TI  - [Predictability of amblyopia in ametropic children. Apropos of 96 cases].
AB  - PURPOSE: The aim of this cross-sectional retrospective study was to analyze the
      predictability of amblyopia in children with myopic and hyperopic unilateral and
      bilateral ametropia. MATERIALS AND METHODS: One hundred and sixty two eyes of 96
      children, (mean age: 8.6 years), were included in this work. Mean visual acuities
      and significant refractive errors were estimated for all the cases. The frequency
      of amblyopia and strabismus was studied in cases without amblyopia and in cases
      with medium and high grade amblyopia. RESULTS: Mean visual acuities were
      significantly higher in cases of bilateral myopia (p < 0.001) and hyperopia (p <
      0.05) compared with unilateral ametropia. The frequency of myopic eyes (p <
      0.01), eyes with high grade of myopia (p < 0.002) and anisomyopic eyes (p <
      0.001) was significantly higher in cases of high amblyopia compared with cases
      without amblyopia. Strabismus (p < 0.05) were also significantly more frequent in
      cases of high amblyopia as well as in cases of myopic eyes (p < 0.01). Moreover,
      in the group of high amblyopia, 6 cases (6/7) had developed an intolerance for
      contact lenses. CONCLUSIONS: The risk of developing high grade amblyopia appeared
      significantly associated with unilateral medium and high level myopia. Strabismus
      and difficulties with good correction of anisometropia by contact lenses or
      spectacle appeared to be predisposing factors. This observation would suggest the
      indication of refractive surgery might be useful in these particular cases. To
      conclude, this study emphasizes the importance of early treatment of ametropia to
      reduce the incidence of amblyopia in children.

PMID- 9759438
TI  - [Oculomotor risk after trans-palpebral bony decompression for thyroid-related
      orbitopathy].
AB  - PURPOSE: To study oculomotor disorders after transpalpebral bony orbital
      decompression (TPBOD) for dysthyroid orbitopathy. Pathophysiology, risk factors,
      preventive and therapeutic care were examined. MATERIAL AND METHODS: Forty-four
      patients were included in this retrospective study (76 orbits). Thirteen patients
      underwent surgery for severe orbital inflammation or optic neuropathy and 31 for
      cosmetic rehabilitation. 21 previously had orbital radiotherapy. Class IV of
      NOSPECS classification, primary position of gaze, diplopia and Lancaster
      coordimetry were studied comparatively pre and postoperatively. RESULTS: Diplopia
      appeared in 23.6% of the cases without deviation before surgery (tropia or phoria
      tropia). Predictive factors were age and amblyopia whereas amount of
      retrodisplacement of the globe and radiotherapy were not. Lack of oculomotor
      restriction did not prevent from diplopia but may decrease its incidence.
      Unilateral decompression is more likely to create a vertical disorder.
      Pathophysiology is discussed. CONCLUSION: Oculomotor disorders can be explained
      by several mechanisms. Some of them can be prevented. Each patient should be
      aware of the risk of diplopia.

PMID- 9759440
TI  - [Retraction nystagmus of vascular origin].
AB  - We report a case of a 42-year-old woman who was referred for diplopia. She
      appeared to have a convergence retraction syndrome and loss of vertical gaze. The
      clinical course led to a diagnosis of thromboembolic cerebrovascular event in the
      region of the posterior commissure on the basis of risk factors such as smoking
      and oral contraceptive use. The final outcome was rapidly favorable.

PMID- 9759439
TI  - [Retinal complications in AIDS patients at the Lome (Togo) University Hospital].
AB  - BACKGROUND: The purpose of this study was to describe retinal complications
      observed in patients presenting with AIDS at Lome teaching hospital. MATERIAL:
      All patients who met WHO AIDS clinical case diagnostic in Africa, admitted for
      various signs in hospital, were followed between December 1996 and May 1997 for
      ocular examinations. RESULTS: We surveyed 94 patients; 41 (43.6%) had retinal
      lesions. Retinal complications were cotton whool spots (30 cases), retinal
      hemorrhages (4 cases), papilloedema (4 cases), cytomegalovirus retinitis (8
      cases). Mortality in patients with retinal complications occurred 10 months after
      the clinical diagnosis of AIDS. CONCLUSION: This study has found a high retinal
      morbidity contrasting with other studies in Africa. This could be explained by
      the longer period of follow-up larger than in previous similar studies.

PMID- 9759441
TI  - [Werner syndrome. Apropos of a case].
AB  - A 26 year-old woman, whose parents were consanguineously married, was admitted to
      our center because of bilateral juvenile cataract. The patient exhibited short
      stature, sclerodermalike appearance of the skin with a typical bird-like facies,
      thinning and graying of hair, high pitched voice and hypogonadism. Werner's
      syndrome, was diagnosed. History, pathogeny, clinical features, diagnosis and
      cataract surgery are discussed.

PMID- 9759442
TI  - [Isolated ocular melanosis. Apropos of a case].
AB  - A case of an eighteen month child with ocular melanocytosis is reported. The
      authors describe clinicopathological features of the affection. Ocular
      melanocytosis is a neural crest disorder more frequently found in pigmented
      populations. Differential diagnosis are naevus of Ota, blue sclera disease and
      scleritis. The risk of malignant degeneration especially in caucasian people
      explain that patient should be followed-up at regular intervals.

PMID- 9759443
TI  - [Cornea plana and severe ametropia].
AB  - Cornea Plana is a bilateral and asymmetric congenital malformation of the corneo
      scleral shape. Corneo-scleral lenses are said to be the preferential treatment.
      We reported the case of a 20-year-old woman, whose Cornea Plana was diagnosed at
      birth, with high hypermetropia and well-corrected with routine spectacles since
      she was 6 months old.

PMID- 9759444
TI  - [Caruncular melanoma. Apropos of clinical case].
AB  - The clinicopathologic case of a 69-year-old-female patient with a big caruncular
      melanoma is reported. Tumor was excised surgically and underwent external
      conventional radiation therapy with no recurrence two years later. Histopathology
      endorsed the clinical diagnosis and thickness of the tumor measured 5.5 mm. The
      bad prognosis of the caruncular location was reinforced by the tumor thickness. A
      better knowledge of conjunctival melanomas characteristics might allow an earlier
      diagnosis and a better prognosis as irradiation following surgical treatment
      appears efficient on unifocal limited melanomas.

PMID- 9759446
TI  - [Pigmented basal cell carcinoma of the eyelid. Apropos of a clinical case].
AB  - A clinico-pathologic case of a 83-year-old female patient with a deeply pigmented
      inferior lid tumor is reported. The histopathological study of the tumor
      demonstrated a pigmented basal cell carcinoma. Numerous different tumors may
      affect the eyelids, melanocytic or not in nature. True melanomas are infrequent
      compared with the numerous other pigmented tumors, which always need a
      histological analysis.

PMID- 9759447
TI  - 7th European Stroke Conference. Edinburgh, United Kingdom, May 27-30, 1998.
      Abstracts.

PMID- 9759448
TI  - 3rd Meeting of the European Society of Neurosonology and Cerebral Hemodynamics.
      Glasgow, United Kingdom, May 24-26, 1998. Abstracts.

PMID- 9759449
TI  - [The 15th Congress of the Ukrainian Physiological Society. Donets'k, Ukraine. May
      12-15, 1998. Abstracts].

PMID- 9759445
TI  - [Actinic keratosis of the conjunctiva. Apropos of a clinical case].
AB  - We report a slowly progressive and whitish limbal conjunctival tumor that
      occurred in a 73-year-old man. An excisional biopsy specimen of this conjunctival
      tumor was submitted for histopathologic evaluation. The diagnosis of conjunctival
      actinic keratosis was based on following cellular abnormalities: epithelial
      hyperplasia acanthosis, keratosis or parakeratosis with discrete papillomatosis
      and some atypia. The basement membrane was intact. An area of elastotic
      degeneration in the subtantia propria, was considered as one of the
      characteristic features of this conjunctival precancerous condition related to
      excessive sun exposure. By hybridization in situ, the detection of human
      papilloma virus (HPV) was negative. Keratosis actinic needs to be distinguished
      from other precancerous conditions showing similar clinical features such as
      dysplasia and carcinoma in situ appearing to affect the prognosis.

PMID- 9759450
TI  - 3rd National Congress of the Italian Society of Medical Andrology. Rome, Italy, 2
      3 April 1998. Abstracts.

PMID- 9759451
TI  - 3rd Joint meeting of the European Society for Dermatological Research, Japanese
      Society for Investigative Dermatology, Society for Investigative Dermatology,
      Cologne, Germany, 7-10 May 1998. Abstracts.

PMID- 9759452
TI  - 25th Annual meeting of the European Thyroid Association. Athens, Greece, May 30
      June 3, 1998. Abstracts.

PMID- 9759454
TI  - XII Panamerican Congress of Rheumatology. Montreal, Quebec, Canada. June 21-25,
      1998. Abstracts.

PMID- 9759453
TI  - Canadian Society of Otolaryngology-Head and Neck Surgery 52nd annual meeting.
      Montreal, Quebec, Canada. June 14-17, 1998. Abstracts.

PMID- 9759455
TI  - 4th International Conference on Functional Mapping of the Human Brain. Montreal,
      Quebec, Canada. June 7-12, 1998. Abstracts.

PMID- 9759456
TI  - 1st Combined International Symposium on Ocular Immunology and Inflammation.
      Amsterdam, The Netherlands, June 27-July 1, 1998. Abstracts.

PMID- 9759457
TI  - XX Congress of the Italian Society of Parasitology. Rome, 17-20 June, 1998.
      Abstracts.

PMID- 9759458
TI  - 82nd Meeting of the German Society of Pathology. Kassel, Germany. 3-6 June 1998.
      Abstracts.

PMID- 9759459
TI  - Cumulative indexes-volumes 51-75.

PMID- 9759460
TI  - 49th Annual meeting of the German Society of Neurosurgery, Hannover, June 12-16,
      1998. Abstracts.

PMID- 9759461
TI  - [Radiation protection in the European Community and in Germany].
AB  - During the last few months, administrations of both the European Community and
      Germany have brought up several recommendations and changes concerning radiation
      protection. The European changes must become national law by 13th May, 2000. The
      changes focus on better protection of children and pregnant women. When
      performing X-ray examinations, strict indications will have to be observed.

PMID- 9759462
TI  - [Pleural drainage in acute thoracic trauma. Comparison of the radiologic image
      and computer tomography].
AB  - PURPOSE: Estimation of chest tube placement in patients with thoracic trauma with
      regard to chest tube malposition in chest radiography in the supine position
      compared to additional computed tomography of the thorax. MATERIAL AND METHODS:
      Apart from compulsory chest radiography after one or multiple chest tube
      insertions, 31 severely injured patients with thoracic trauma underwent a CT scan
      of the thorax. These 31 patients with 40 chest tubes constituted the basis for
      the present analysis. RESULTS: In chest radiography in the supine position there
      were no chest tube malpositions (n = 40); In the CT scans 25 correct positions, 7
      pseudo-malpositions, 6 intrafissural and 2 intrapulmonary malpositions were
      identified. Moreover 16 sufficient, 18 insufficient and 6 indifferent functions
      of the chest tubes were seen. CONCLUSION: In case of lasting clinical problems
      and questionable function of the chest tube, chest radiography should be
      supplemented by a CT scan of the thorax in order to estimate the position of the
      chest tube.

PMID- 9759463
TI  - [Multi-project angiography in the imaging of cerebral aneurysm].
AB  - In spite of procedures such as CT angiography, MR angiography, and rotation
      angiography, panangiography is still indispensable in therapeutic planning for
      cerebral aneurysms. It is the only method that provides exact details about the
      size, anatomic localization, and multiplicity of aneurysms as well as relation to
      surrounding vessels, the presence of an aneurysmal neck, and for the evaluation
      of the collateral circulation required to answer the question if endovascular
      therapy is possible. In addition, panangiography still exhibits the highest
      selectivity in the detection of cerebral aneurysms.

PMID- 9759464
TI  - [3-phase spiral CT of the liver, Value of non-contrast arterial and portal venous
      studies in the diagnosis of focal liver lesions].
AB  - PURPOSE: To assess the value of noncontrast, arterial and portal venous phase of
      triphasic helical CT in detecting and characterising focal liver lesions.
      MATERIAL AND METHODS: 120 patients with focal liver disease underwent triphasic
      helical CT examinations with a collimation of 6.5 mm at a table feed of 6.5 mm/s.
      The liver scans were obtained before the administration of 120 ml of non-ionic
      contrast material (flow 2 or 3 ml/s), at the arterial phase, and at the portal
      venous phase (20 s, respectively 60 s after injection). Patients were divided
      into four groups according to the underlying disease and enhancement pattern. The
      studies were evaluated retrospectively. RESULTS: A total of 269 lesions was seen.
      The noncontrast phase (NCP) revealed 86% of lesions, the arterial phase (AP) 95%
      and the portal venous phase (PVP) 91%. In the first group of hypovascular lesions
      (colorectal carcinoma) all lesions (73/73) were detected in the PVP. In the
      second group of hypervascular lesions (breast cancer, melanoma) the combination
      of AP and PVP revealed 73 of 74 lesions. In the third group of patients with
      unknown primary and detected lesions by sonography all 89 lesions were detected
      with the combination of AP and PVP. In the fourth group of patients with
      cirrhosis 3 of 33 lesions were detected exclusively during the AP and 3 other
      lesions exclusively during the NCP. To make a definitive diagnosis of focal liver
      lesions the value of the three phases was as follows: to characterise lesions the
      PVP was sufficient in 62%, the combination of PVP and AP in 27%, and the
      combination of all three phases in 11%. CONCLUSIONS: If hypovascular lesions are
      suspected examination during PVP is sufficient. In cases of hypervascular lesions
      and lesions of unknown primary AP and PVP should be combined. Unenhanced scans
      are of additional diagnostic value only in patients with liver cirrhosis.

PMID- 9759465
TI  - [MRI in typical and atypical aortic dissection].
AB  - PURPOSE: To determine the value of MRI in typical and atypical aortic
      dissections. METHODS: MRI investigations on 16 patients with aortic dissections
      were analysed retrospectively; for 8 patients CT investigations carried out at
      almost the same time were available for comparison. RESULTS: In all cases the
      diagnosis of aortic dissection was possible from MRI and CT. If a dissection
      membrane and a double lumen were present these were detected in all patients by
      both methods. In three patients with atypical dissections, only an asymmetrical
      abnormal wall thickening as sole sign for the presence of an aortic dissection
      was seen. A differentiation between true and false lumen was possible in 16 of 17
      MRI investigations and in 5 of 8 CT investigations on the basis of differing
      blood flow velocities or, respectively, the detection of a thrombus in the false
      lumen. The relationship of the dissection membrane to the large aortic branches
      as well as the determination of the branch vessel origin with regard to true or
      false lumen could be evaluated better with MRI than with CT. CONCLUSIONS: Thus
      MRI has a significant role in the diagnosis and follow-up of aortic dissections.
      The advantage in comparison to the alternative spiral CT technique is, in
      addition to the absence of radiation exposure, the better analysis of the extent
      of the dissection as a result of the multi-planar slice orientation (especially
      in the region of the aortic arch and the arch vessel origins) without the
      necessity to administer iodine-containing contrast media.

PMID- 9759466
TI  - [Clinical aspects of image quality and doses in gated pulsed imaging].
AB  - PURPOSE: The relations between image quality in last image hold images and dose
      in grid controlled fluoroscopy in comparison to the continuous mode need to be
      characterised and recommendations for the clinical application of this technique
      should be given. MATERIAL AND METHODS: Spatial resolution, signal-noise ratio
      and, contrast-detail visibility were evaluated by phantom measurements in grid
      controlled pulsed and continuous fluoroscopy. Dose was measured at the image
      intensifier entrance. Image quality of last image hold (LIH) images of clinical
      examinations was graded in relation to single shot exposures. RESULTS: Signal
      noise ratio and contrast-detail visibility depend on the dose per puls. Spatial
      resolution and contrast-detail visibility in grid controlled fluoroscopy are
      superior than to in the continuous mode. Image quality of the LIH images from the
      grid controlled fluoroscopy was improved. Radiation exposure could be reduced to
      10-46%. CONCLUSIONS: Combinations of puls-dose and -frequency are recommended for
      achieving extensive dose reduction and improved image quality of LIH images.

PMID- 9759467
TI  - [Radiation-induced osteonecrosis of the pelvic bones vs. bone metastases--a
      difficult differential diagnosis].
AB  - BACKGROUND: Since the introduction of megavoltage radiation therapy radiation
      osteitis has become a rare event and may be easily mistaken for bone metastases.
      A case of radiation osteitis is reported and diagnostic features are discussed.
      CASE REPORT: A 70 year-old female patient underwent rectum resection for rectum
      cancer and was given standard adjuvant therapy consisting of irradiation of the
      tumor site and lymph nodes in the pelvis with 18 MeV photons, boxfield technique
      up to 50.4 Gy and chemotherapy with 5-FU. Eight months later she complained of
      severe lower back pain. Plain radiographs and CT revealed osteolytic lesions in
      the ileosacral joints and os sacrum which appeared as circumscript areas of
      signal loss in MRI (T1-weighted sequence). A soft tissue mass was not detected.
      CT-guided biopsy excluded bone metastases. CONCLUSION: Characteristic features of
      radiation osteitis are spongiosa destructions initially in weight-bearing bones
      within the radiation field, namely the ileosacral joints, and the lack of
      pathologic soft tissue mass. False treatment, i.e. radiation for bone metastases,
      should be avoidable.

PMID- 9759468
TI  - [Pseudo-rupture of the femoral artery following balloon angioplasty].
AB  - Following PTA of a superficial femoral artery stenosis, painful swelling of the
      vastus medialis muscle occurred at mobilization of the patient 24 hours after the
      intervention. Duplex sonography and angiography revealed bleeding from a muscular
      branch of the SFA. The complication was successfully treated by embolization.

PMID- 9759469
TI  - [Barium aspiration with fatal outcome].
AB  - A female patient died after aspiration of a barium-containing contrast medium as
      a result of ARDS in spite of intensive medical care. In cases of aspiration, the
      degree of aspiration should be documented by X-ray as soon as possible in order
      to decide upon the extent of specific suction measure. Lethalities after
      aspiration may be more frequent than can be assumed from the reports in the
      literature.

PMID- 9759470
TI  - [Bullet embolism in the right pulmonary artery].
AB  - We report about a bullet embolus in the middle lobe pulmonary artery (a patient
      who was sent for a routine-chest-film preoperatively). The patient, 74 years old,
      was hit by a bullet in localization of the left masseteric region during world
      war II. The bullet entered the left Vena jugularis and was embolised into the
      middle lobe pulmonary artery (shock-position). By the means of CT-curved
      reformations we could localize the bullet (2 x 0.7 cm) in the middle lobe
      pulmonary artery and diagnosed a lobar fibrosis as a sequel of the focal
      hypoxemia.

PMID- 9759471
TI  - Cytogenetic and molecular investigations of Y chromosome sequences and their role
      in Turner syndrome.
AB  - It has been proposed that all live born females with Turner syndrome carry a cell
      line containing two sex chromosomes, which may be present at a low level of
      mosaicism (Hook & Warburton, 1983; Hassold et al. 1985; 1988; Connor & Loughlin,
      1989). If the second sex chromosome is a Y, these patients are at risk of
      developing gonadoblastoma. In this study, 50 patients found to have a 45,X
      karyotype by conventional cytogenetic analysis, were screened by the polymerase
      chain reaction (PCR), for the presence of Y chromosome sequences. Two patients
      were positive for six of the eight Y chromosome loci tested and additional
      cytogenetic analysis confirmed the presence of a marker chromosome, in 8% and 3%
      of cells respectively. Fluorescence in situ hybridization (FISH) was used to
      confirm that the markers were of Y chromosome origin and helped to elucidate
      their structure. In addition, four other patients were found to have a Y
      chromosome by initial routine cytogenetic analysis. FISH, in conjunction with
      PCR, elucidated the structure of the Y chromosomes. This study illustrates the
      value of using a combination of cytogenetic and molecular techniques, to identify
      Y chromosome sequences in Turner syndrome.

PMID- 9759472
TI  - A splicing mutation of the RHAG gene associated with the Rhnull phenotype.
AB  - Rhnull is a syndrome serologically characterized by the deficiency of all Rh
      antigens on human red blood cells. Rhnull is divided into two types: regulator
      and amorph. Recently, Cherif-Zahar et al. proposed that the RHAG gene encoding
      the Rh50 glycoprotein is a candidate for inducing regulator type Rhnull. We
      investigated both the RH and RHAG genes in an Rhnull individual. The
      reticulocytes from the propositus had RHD, RHcE, and RHCe transcripts without any
      mutation. However, the sequence analysis of RHAG cDNA showed a deletion of 122 bp
      from nucleotide 946 to 1067. This deletion was revealed to be due to a homozygous
      splicing mutation, which is a single base substitution at the consensus sequence
      of the splicing acceptor site (AG-->AT). The mutation appeared to break the 'GT
      AG' splicing rule and to cause 122 bp exon skipping accompanied by a frameshift.
      This study confirms that the RHAG gene is the most likely candidate for the
      'regulator' gene of Rhnull cases.

PMID- 9759473
TI  - Age-related changes of the 3'APOB-VNTR genotype pool in ageing cohorts.
AB  - The analysis of seven different age cohorts (697 individuals from 10 to 109 years
      old) revealed age-related changes in the 3'APOB-VNTR genotype pool. By recoding
      the 3'APOB-VNTR alleles into three size-classes (small, S, 26-34 repeats; medium,
      M, 35-39 repeats; large, L, 41-55 repeats), an age-related convex trajectory of
      the frequency of SS homozygotes was found. The frequency of SS in the genotype
      pool increased from the group aged 10-19 years (3.06 +/- 1.74%) to that aged 40
      49 years (8.51 +/- 4.07%). Then it declined reaching the minimum value in
      centenarians (1.58 +/- 0.90%). The observed trajectory is in agreement with that
      expected by assuming crossing of mortality curves relevant to subgroups of
      individuals having different genotypes.

PMID- 9759474
TI  - HLA evidence for the lack of genetic heterogeneity in Basques.
AB  - To examine the possible internal heterogeneity within the Basque population, nine
      samples typed for several HLA loci were compiled and HLA-A, B, C and DR loci were
      analysed. First, the shared features of HLA in Basques were analysed by principal
      component analysis and genetic distances. Two major Basque dialect groups
      ('French' and 'Spanish') were considered. FST statistics were computed and
      corrected for sampling intensity. The dialectal and political division did not
      seem to differentiate these two groups genetically. Analysis of Molecular
      Variance also failed to show consistently significant genetic variance components
      between French and Spanish Basques. Thus, in this particular example, linguistic
      diversity does not seem to correlate with a genetic stratification.

PMID- 9759475
TI  - Diversity in protein, nuclear DNA, and mtDNA in South Amerinds--agreement or
      discrepancy?
AB  - Two sets of markers and populations were considered in this study: (a) the
      variability at 17 protein loci and in the sequences of the first hypervariable
      segment of the mitochondrial DNA (mtDNA) were compared in 10 South American
      Indian tribes, in a total 3016 and 241 individuals, respectively; and (b) a
      triple comparison was made, in relation to 17 protein, mtDNA and six
      hypervariable tandem repeat loci in four Brazilian Indian tribes, involving 1567,
      56 and 194 persons, respectively. Both the intrapopulational diversities and the
      population relationships obtained in these groups with these different sets of
      markers showed no significant correlation. High levels of heterogeneity were
      observed both at the protein and hypervariable individual loci, as well between
      mtDNA sites. The different positions observed for the Yanomama (but not for the
      other nine tribes) in the trees which summarized the protein and mtDNA data
      suggest some degree of asymmetric interchange related to sex between them and
      neighbouring tribes.

PMID- 9759476
TI  - The role of consanguinity and inbreeding as a determinant of spontaneous abortion
      in Karachi, Pakistan.
AB  - The effect of consanguinity and inbreeding on spontaneous abortion is assessed
      with the help of data from a population-based study conducted in four squatter
      settlements of Karachi, Pakistan. The analysis is based on 4966 pregnancy records
      belonging to 873 women. Results of the multivariate analysis show that both
      consanguinity and inbreeding were independent risk factors for spontaneous
      abortion despite undertaking control for other biological and socio-demographic
      factors that could confound the association. The combination of fetal and
      parental inbreeding led to a greater likelihood of a pregnancy ending in
      spontaneous abortion than one generation of inbreeding alone.

PMID- 9759477
TI  - Hidden linkage: a comparison of the affected sib pair (ASP) test and
      transmission/disequilibrium test (TDT).
AB  - I compare the transmission/disequilibrium test (TDT) and affected sib pair (ASP)
      test under a general algebraic model describing a bi-allelic disease locus.
      Assuming linkage to a bi-allelic marker, I derive two binomial probabilities, one
      for parental allele 'transmission' (Pt) which determines the magnitude of the TDT
      chi 2 statistic (chi 2tdt), and a second for identity-by-descent (ibd) marker
      allele 'sharing' (Ps) which determines the magnitude of the ASP test statistic
      (chi 2asp). I also consider the ASP test applied to a completely polymorphic
      marker and demonstrate that the probability of ASP marker allele sharing (Ps) is
      identical to Ps observed for a bi-allelic marker in equilibrium with the disease
      locus. I present a general framework for determining the power of the TDT and ASP
      test based on expressions for Pt, Ps and the proportion (H/F) of ascertained
      parents who are informative at the marker. Two previous analytic investigations
      of TDT power based on the work of Ott (1989), and Risch & Merikangas (1996) are
      shown to be special cases of this general framework. In addition, I show the
      relationship between the framework I present and a third analytic investigation
      of TDT power for multi-allelic markers based on the work of Sham & Curtis (1995).

PMID- 9759478
TI  - Characterization of polymorphisms at the 11 beta-hydroxylase (CYP11B1) locus.
AB  - Four sequence variants in the 11 beta-hydroxylase (CYP11B1) gene are reported.
      One of the sequence changes occurs in exon 1 and is in linkage disequilibrium
      with a second variant in intron 3. The other two changes occur at adjacent
      nucleotides in intron 1. The finding of easily demonstrable, intragenic variants
      will be beneficial to the study of the role of the CYP11B1 and the adjacent
      aldosterone synthase (CYP11B2) gene in hypertensive disease.

PMID- 9759479
TI  - An accidental biochemist.

PMID- 9759480
TI  - HIV-1: fifteen proteins and an RNA.
AB  - Human immunodeficiency virus type 1 is a complex retrovirus encoding 15 distinct
      proteins. Substantial progress has been made toward understanding the function of
      each protein, and three-dimensional structures of many components, including
      portions of the RNA genome, have been determined. This review describes the
      function of each component in the context of the viral life cycle: the Gag and
      Env structural proteins MA (matrix), CA (capsid), NC (nucleocapsid), p6, SU
      (surface), and TM (transmembrane); the Pol enzymes PR (protease), RT (reverse
      transcriptase), and IN (integrase); the gene regulatory proteins Tat and Rev; and
      the accessory proteins Nef, Vif, Vpr, and Vpu. The review highlights recent
      biochemical and structural studies that help clarify the mechanisms of viral
      assembly, infection, and replication.

PMID- 9759481
TI  - Sphingolipid functions in Saccharomyces cerevisiae: comparison to mammals.
AB  - Many roles for sphingolipids have been identified in mammals. Available data
      suggest that sphingolipids and their intermediates also have diverse roles in
      Saccharomyces cerevisiae. These roles include signal transduction during the heat
      stress response, regulation of calcium homeostasis or components in calcium
      mediated signaling pathways, regulation of the cell cycle, and functions as
      components in trafficking of secretory vesicles from the endoplasmic reticulum to
      the Golgi apparatus and as the lipid moiety in many glycosylphosphatidylinositol
      anchored proteins. S. cerevisiae is likely to be the first organism in which all
      genes involved in sphingolipid metabolism are identified. This information will
      provide an unprecedented opportunity to determine, for the first time in any
      organism, how sphingolipid synthesis is regulated. Through the use of both
      genetic and biochemical techniques, the identification of the complete array of
      processes regulated by sphingolipid signals is likely to be possible, as is the
      quantification of the physiological contribution of each.

PMID- 9759482
TI  - Transporters of nucleotide sugars, ATP, and nucleotide sulfate in the endoplasmic
      reticulum and Golgi apparatus.
AB  - The lumens of the endoplasmic reticulum and Golgi apparatus are the subcellular
      sites where glycosylation, sulfation, and phosphorylation of secretory and
      membrane-bound proteins, proteoglycans, and lipids occur. Nucleotide sugars,
      nucleotide sulfate, and ATP are substrates for these reactions. ATP is also used
      as an energy source in the lumen of the endoplasmic reticulum during protein
      folding and degradation. The above nucleotide derivatives and ATP must first be
      translocated across the membrane of the endoplasmic reticulum and/or Golgi
      apparatus before they can serve as substrates in the above lumenal reactions.
      Translocation of the above solutes is mediated for highly specific transporters,
      which are antiporters with the corresponding nucleoside monophosphates as shown
      by biochemical and genetic approaches. Mutants in mammals, yeast, and protozoa
      showed that a defect in a specific translocator activity results in selective
      impairments of the above posttranslational modifications, including loss of
      virulence of pathogenic protozoa. Several of these transporters have been
      purified and cloned. Experiments with yeast and mammalian cells demonstrate that
      these transporters play a regulatory role in the above reactions. Future studies
      will address the structure of the above proteins, how they are targeted to
      different organelles, their potential as drug targets, their role during
      development, and the possible occurrence of specific diseases.

PMID- 9759483
TI  - Ribonucleotide reductases.
AB  - Ribonucleotide reductases provide the building blocks for DNA replication in all
      living cells. Three different classes of enzymes use protein free radicals to
      activate the substrate. Aerobic class I enzymes generate a tyrosyl radical with
      an iron-oxygen center and dioxygen, class II enzymes employ adenosylcobalamin,
      and the anaerobic class III enzymes generate a glycyl radical from S
      adenosylmethionine and an iron-sulfur cluster. The X-ray structure of the class I
      Escherichia coli enzyme, including forms that bind substrate and allosteric
      effectors, confirms previous models of catalytic and allosteric mechanisms. This
      structure suggests considerable mobility of the protein during catalysis and,
      together with experiments involving site-directed mutants, suggests a mechanism
      for radical transfer from one subunit to the other. Despite large differences
      between the classes, common catalytic and allosteric mechanisms, as well as
      retention of critical residues in the protein sequence, suggest a similar
      tertiary structure and a common origin during evolution. One puzzling aspect is
      that some organisms contain the genes for several different reductases.

PMID- 9759484
TI  - Modified oligonucleotides: synthesis and strategy for users.
AB  - Synthetic oligonucleotide analogs have greatly aided our understanding of several
      biochemical processes. Efficient solid-phase and enzyme-assisted synthetic
      methods and the availability of modified base analogs have added to the utility
      of such oligonucleotides. In this review, we discuss the applications of
      synthetic oligonucleotides that contain backbone, base, and sugar modifications
      to investigate the mechanism and stereochemical aspects of biochemical reactions.
      We also discuss interference mapping of nucleic acid-protein interactions;
      spectroscopic analysis of biochemical reactions and nucleic acid structures; and
      nucleic acid cross-linking studies. The automation of oligonucleotide synthesis,
      the development of versatile phosphoramidite reagents, and efficient scale-up
      have expanded the application of modified oligonucleotides to diverse areas of
      fundamental and applied biological research. Numerous reports have covered
      oligonucleotides for which modifications have been made of the phosphodiester
      backbone, of the purine and pyrimidine heterocyclic bases, and of the sugar
      moiety; these modifications serve as structural and mechanistic probes. In this
      chapter, we review the range, scope, and practical utility of such chemically
      modified oligonucleotides. Because of space limitations, we discuss only those
      oligonucleotides that contain phosphate and phosphate analogs as internucleotidic
      linkages.

PMID- 9759485
TI  - The molecular control of circadian behavioral rhythms and their entrainment in
      Drosophila.
AB  - Molecular and genetic characterizations of circadian rhythms in Drosophila
      indicate that function of an intracellular pacemaker requires the activities of
      proteins encoded by three genes: period (per), timeless (tim), and doubletime
      (dbt). RNA from two of these genes, per and tim, is expressed with a circadian
      rhythm. Heterodimerization of PER and TIM proteins allows nuclear localization
      and suppression of further RNA synthesis by a PER/TIM complex. These protein
      interactions promote cyclical gene expression because heterodimers are observed
      only at high concentrations of per and tim RNA, separating intervals of RNA
      accumulation from times of PER/TIM complex activity. Light resets these molecular
      cycles by eliminating TIM. The product of dbt also regulates accumulation of per
      and tim RNA, and it may influence action of the PER/TIM complex. The recent
      discovery of PER homologues in mice and humans suggests that a related mechanism
      controls mammalian circadian behavioral rhythms.

PMID- 9759486
TI  - Ribonuclease P: unity and diversity in a tRNA processing ribozyme.
AB  - Ribonuclease P (RNase P) is the endoribonuclease that generates the mature 5'
      ends of tRNA by removal of the 5'-leader elements of precursor-tRNAs. This enzyme
      has been characterized from representatives of all three domains of life
      (Archaea, Bacteria, and Eucarya) (1) as well as from mitochondria and
      chloroplasts. The cellular and mitochondrial RNase Ps are ribonucleoproteins,
      whereas the most extensively studied chloroplast RNase P (from spinach) is
      composed solely of protein. Remarkably, the RNA subunit of bacterial RNase P is
      catalytically active in vitro in the absence of the protein subunit (2). Although
      RNA-only activity has not been demonstrated for the archael, eucaryal, or
      mitochondrial RNAs, comparative sequence analysis has established that these RNAs
      are homologous (of common ancestry) to bacterial RNA. RNase P holoenzymes vary
      greatly in organizational complexity across the phylogenetic domains, primarily
      because of differences in the RNase P protein subunits: Mitochondrial, archaeal,
      and eucaryal holoenzymes contain larger, and perhaps more numerous, protein
      subunits than do the bacterial holoenzymes. However, that the nonbacterial RNase
      P RNAs retain significant structural similarity to their catalytically active
      bacterial counterparts indicates that the RNA remains the catalytic center of the
      enzyme.

PMID- 9759487
TI  - Base flipping.
AB  - Base flipping is the phenomenon whereby a base in normal B-DNA is swung
      completely out of the helix into an extrahelical position. It was discovered in
      1994 when the first co-crystal structure was reported for a cytosine-5 DNA
      methyltransferase binding to DNA. Since then it has been shown to occur in many
      systems where enzymes need access to a DNA base to perform chemistry on it. Many
      DNA glycosylases that remove abnormal bases from DNA use this mechanism. This
      review describes systems known to use base flipping as well as many systems where
      it is likely to occur but has not yet been rigorously demonstrated. The mechanism
      and evolution of base flipping are also discussed.

PMID- 9759488
TI  - The caveolae membrane system.
AB  - The cell biology of caveolae is a rapidly growing area of biomedical research.
      Caveolae are known primarily for their ability to transport molecules across
      endothelial cells, but modern cellular techniques have dramatically extended our
      view of caveolae. They form a unique endocytic and exocytic compartment at the
      surface of most cells and are capable of importing molecules and delivering them
      to specific locations within the cell, exporting molecules to extracellular
      space, and compartmentalizing a variety of signaling activities. They are not
      simply an endocytic device with a peculiar membrane shape but constitute an
      entire membrane system with multiple functions essential for the cell. Specific
      diseases attack this system: Pathogens have been identified that use it as a
      means of gaining entrance to the cell. Trying to understand the full range of
      functions of caveolae challenges our basic instincts about the cell.

PMID- 9759489
TI  - How cells respond to interferons.
AB  - Interferons play key roles in mediating antiviral and antigrowth responses and in
      modulating immune response. The main signaling pathways are rapid and direct.
      They involve tyrosine phosphorylation and activation of signal transducers and
      activators of transcription factors by Janus tyrosine kinases at the cell
      membrane, followed by release of signal transducers and activators of
      transcription and their migration to the nucleus, where they induce the
      expression of the many gene products that determine the responses. Ancillary
      pathways are also activated by the interferons, but their effects on cell
      physiology are less clear. The Janus kinases and signal transducers and
      activators of transcription, and many of the interferon-induced proteins, play
      important alternative roles in cells, raising interesting questions as to how the
      responses to the interferons intersect with more general aspects of cellular
      physiology and how the specificity of cytokine responses is maintained.

PMID- 9759490
TI  - Nucleocytoplasmic transport: the soluble phase.
AB  - Active transport between the nucleus and cytoplasm involves primarily three
      classes of macromolecules: substrates, adaptors, and receptors. Some transport
      substrates bind directly to an import or an export receptor while others require
      one or more adaptors to mediate formation of a receptor-substrate complex. Once
      assembled, these transport complexes are transferred in one direction across the
      nuclear envelope through aqueous channels that are part of the nuclear pore
      complexes (NPCs). Dissociation of the transport complex must then take place, and
      both adaptors and receptors must be recycled through the NPC to allow another
      round of transport to occur. Directionality of either import or export therefore
      depends on association between a substrate and its receptor on one side of the
      nuclear envelope and dissociation on the other. The Ran GTPase is critical in
      generating this asymmetry. Regulation of nucleocytoplasmic transport generally
      involves specific inhibition of the formation of a transport complex; however,
      more global forms of regulation also occur.

PMID- 9759491
TI  - Role of small G proteins in yeast cell polarization and wall biosynthesis.
AB  - In the vegetative (mitotic) cycle and during sexual conjugation, yeast cells
      display polarized growth, giving rise to a bud or to a mating projection,
      respectively. In both cases one can distinguish three steps in these processes:
      choice of a growth site, organization of the growth site, and actual growth and
      morphogenesis. In all three steps, small GTP-binding proteins (G proteins) and
      their regulators play essential signaling functions. For the choice of a bud
      site, Bud1, a small G protein, Bud2, a negative regulator of Bud1, and Bud5, an
      activator, are all required. If any of them is defective, the cell loses its
      ability to select a proper bud position and buds randomly. In the organization of
      the bud site or of the site in which a mating projection appears, Cdc42, its
      activator Cdc24, and its negative regulators play a fundamental role. In the
      absence of Cdc42 or Cdc24, the actin cytoskeleton does not become organized and
      budding does not take place. Finally, another small G protein, Rho1, is required
      for activity of beta (1-->3)glucan synthase, the enzyme that catalyzes the
      synthesis of the major structural component of the yeast cell wall. In all of the
      above processes, G proteins can work as molecular switches because of their
      ability to shift between an active GTP-bound state and an inactive GDP-bound
      state.

PMID- 9759492
TI  - RNA localization in development.
AB  - Cytoplasmic RNA localization is an evolutionarily ancient mechanism for producing
      cellular asymmetries. This review considers RNA localization in the context of
      animal development. Both mRNAs and non-protein-coding RNAs are localized in
      Drosophila, Xenopus, ascidian, zebrafish, and echinoderm oocytes and embryos, as
      well as in a variety of developing and differentiated polarized cells from yeast
      to mammals. Mechanisms used to transport and anchor RNAs in the cytoplasm include
      vectorial transport out of the nucleus, directed cytoplasmic transport in
      association with the cytoskeleton, and local entrapment at particular cytoplasmic
      sites. The majority of localized RNAs are targeted to particular cytoplasmic
      regions by cis-acting RNA elements; in mRNAs these are almost always in the 3'
      untranslated region (UTR). A variety of trans-acting factors--many of them RNA
      binding proteins--function in localization. Developmental functions of RNA
      localization have been defined in Xenopus, Drosophila, and Saccharomyces
      cerevisiae. In Drosophila, localized RNAs program the antero-posterior and dorso
      ventral axes of the oocyte and embryo. In Xenopus, localized RNAs may function in
      mesoderm induction as well as in dorso-ventral axis specification. Localized RNAs
      also program asymmetric cell fates during Drosophila neurogenesis and yeast
      budding.

PMID- 9759493
TI  - Biochemistry and genetics of von Willebrand factor.
AB  - Von Willebrand factor (VWF) is a blood glycoprotein that is required for normal
      hemostasis, and deficiency of VWF, or von Willebrand disease (VWD), is the most
      common inherited bleeding disorder. VWF mediates the adhesion of platelets to
      sites of vascular damage by binding to specific platelet membrane glycoproteins
      and to constituents of exposed connective tissue. These activities appear to be
      regulated by allosteric mechanisms and possibly by hydrodynamic shear forces. VWF
      also is a carrier protein for blood clotting factor VIII, and this interaction is
      required for normal factor VIII survival in the circulation. VWF is assembled
      from identical approximately 250 kDa subunits into disulfide-linked multimers
      that may be > 20,000 kDa. Mutations in VWD can disrupt this complex biosynthetic
      process at several steps to impair the assembly, intracellular targeting, or
      secretion of VWF multimers. Other VWD mutations impair the survival of VWF in
      plasma or the function of specific ligand binding sites. This growing body of
      information about VWF synthesis, structure, and function has allowed the
      reclassification of VWD based upon distinct pathophysiologic mechanisms that
      appear to correlate with clinical symptoms and the response to therapy.

PMID- 9759494
TI  - The ubiquitin system.
AB  - The selective degradation of many short-lived proteins in eukaryotic cells is
      carried out by the ubiquitin system. In this pathway, proteins are targeted for
      degradation by covalent ligation to ubiquitin, a highly conserved small protein.
      Ubiquitin-mediated degradation of regulatory proteins plays important roles in
      the control of numerous processes, including cell-cycle progression, signal
      transduction, transcriptional regulation, receptor down-regulation, and
      endocytosis. The ubiquitin system has been implicated in the immune response,
      development, and programmed cell death. Abnormalities in ubiquitin-mediated
      processes have been shown to cause pathological conditions, including malignant
      transformation. In this review we discuss recent information on functions and
      mechanisms of the ubiquitin system. Since the selectivity of protein degradation
      is determined mainly at the stage of ligation to ubiquitin, special attention is
      focused on what we know, and would like to know, about the mode of action of
      ubiquitin-protein ligation systems and about signals in proteins recognized by
      these systems.

PMID- 9759495
TI  - Phosphoinositide kinases.
AB  - Phosphatidylinositol, a component of eukaryotic cell membranes, is unique among
      phospholipids in that its head group can be phosphorylated at multiple free
      hydroxyls. Several phosphorylated derivatives of phosphatidylinositol,
      collectively termed phosphoinositides, have been identified in eukaryotic cells
      from yeast to mammals. Phosphoinositides are involved in the regulation of
      diverse cellular processes, including proliferation, survival, cytoskeletal
      organization, vesicle trafficking, glucose transport, and platelet function. The
      enzymes that phosphorylate phosphatidylinositol and its derivatives are termed
      phosphoinositide kinases. Recent advances have challenged previous hypotheses
      about the substrate selectivity of different phosphoinositide kinase families.
      Here we re-examine the pathways of phosphoinositide synthesis and the enzymes
      involved.

PMID- 9759496
TI  - The green fluorescent protein.
AB  - In just three years, the green fluorescent protein (GFP) from the jellyfish
      Aequorea victoria has vaulted from obscurity to become one of the most widely
      studied and exploited proteins in biochemistry and cell biology. Its amazing
      ability to generate a highly visible, efficiently emitting internal fluorophore
      is both intrinsically fascinating and tremendously valuable. High-resolution
      crystal structures of GFP offer unprecedented opportunities to understand and
      manipulate the relation between protein structure and spectroscopic function. GFP
      has become well established as a marker of gene expression and protein targeting
      in intact cells and organisms. Mutagenesis and engineering of GFP into chimeric
      proteins are opening new vistas in physiological indicators, biosensors, and
      photochemical memories.

PMID- 9759497
TI  - Alteration of nucleosome structure as a mechanism of transcriptional regulation.
AB  - The nucleosome, which is the primary building block of chromatin, is not a static
      structure: It can adopt alternative conformations. Changes in solution conditions
      or changes in histone acetylation state cause nucleosomes and nucleosomal arrays
      to behave with altered biophysical properties. Distinct subpopulations of
      nucleosomes isolated from cells have chromatographic properties and nuclease
      sensitivity different from those of bulk nucleosomes. Recently, proteins that
      were initially identified as necessary for transcriptional regulation have been
      shown to alter nucleosomal structure. These proteins are found in three types of
      multiprotein complexes that can acetylate nucleosomes, deacetylate nucleosomes,
      or alter nucleosome structure in an ATP-dependent manner. The direct modification
      of nucleosome structure by these complexes is likely to play a central role in
      appropriate regulation of eukaryotic genes.

PMID- 9759498
TI  - Structure and function in GroEL-mediated protein folding.
AB  - Recent structural and biochemical investigations have come together to allow a
      better understanding of the mechanism of chaperonin (GroEL, Hsp60)-mediated
      protein folding, the final step in the accurate expression of genetic
      information. Major, asymmetric conformational changes in the GroEL double toroid
      accompany binding of ATP and the cochaperonin GroES. When a nonnative
      polypeptide, bound to one of the GroEL rings, is encapsulated by GroES to form a
      cis ternary complex, these changes drive the polypeptide into the sequestered
      cavity and initiate its folding. ATP hydrolysis in the cis ring primes release of
      the products, and ATP binding in the trans ring then disrupts the cis complex.
      This process allows the polypeptide to achieve its final native state, if folding
      was completed, or to recycle to another chaperonin molecule, if the folding
      process did not result in a form committed to the native state.

PMID- 9759499
TI  - Matrix proteoglycans: from molecular design to cellular function.
AB  - The proteoglycan superfamily now contains more than 30 full-time molecules that
      fulfill a variety of biological functions. Proteoglycans act as tissue
      organizers, influence cell growth and the maturation of specialized tissues, play
      a role as biological filters and modulate growth-factor activities, regulate
      collagen fibrillogenesis and skin tensile strength, affect tumor cell growth and
      invasion, and influence corneal transparency and neurite outgrowth. Additional
      roles, derived from studies of mutant animals, indicate that certain
      proteoglycans are essential to life whereas others might be redundant. The review
      focuses on the most recent genetic and molecular biological studies of the matrix
      proteoglycans, broadly defined as proteoglycans secreted into the pericellular
      matrix. Special emphasis is placed on the molecular organization of the protein
      core, the utilization of protein modules, the gene structure and transcriptional
      control, and the functional roles of the various proteoglycans. When possible,
      proteoglycans have been grouped into distinct gene families and subfamilies
      offering a simplified nomenclature based on their protein core design. The
      structure-function relationship of some paradigmatic proteoglycans is discussed
      in depth and novel aspects of their biology are examined.

PMID- 9759500
TI  - G protein-coupled receptor kinases.
AB  - G protein-coupled receptor kinases (GRKs) constitute a family of six mammalian
      serine/threonine protein kinases that phosphorylate agonist-bound, or activated,
      G protein-coupled receptors (GPCRs) as their primary substrates. GRK-mediated
      receptor phosphorylation rapidly initiates profound impairment of receptor
      signaling, or desensitization. This review focuses on the regulation of GRK
      activity by a variety of allosteric and other factors: agonist-stimulated GPCRs,
      beta gamma subunits of heterotrimeric GTP-binding proteins, phospholipid
      cofactors, the calcium-binding proteins calmodulin and recoverin,
      posttranslational isoprenylation and palmitoylation, autophosphorylation, and
      protein kinase C-mediated GRK phosphorylation. Studies employing recombinant,
      purified proteins, cell culture, and transgenic animal models attest to the
      general importance of GRKs in regulating a vast array of GPCRs both in vitro and
      in vivo.

PMID- 9759501
TI  - Enzymatic transition states and transition state analog design.
AB  - All chemical transformations pass through an unstable structure called the
      transition state, which is poised between the chemical structures of the
      substrates and products. The transition states for chemical reactions are
      proposed to have lifetimes near 10(-13) sec, the time for a single bond
      vibration. No physical or spectroscopic method is available to directly observe
      the structure of the transition state for enzymatic reactions. Yet transition
      state structure is central to understanding catalysis, because enzymes function
      by lowering activation energy. An accepted view of enzymatic catalysis is tight
      binding to the unstable transition state structure. Transition state mimics bind
      tightly to enzymes by capturing a fraction of the binding energy for the
      transition state species. The identification of numerous transition state
      inhibitors supports the transition state stabilization hypothesis for enzymatic
      catalysis. Advances in methods for measuring and interpreting kinetic isotope
      effects and advances in computational chemistry have provided an experimental
      route to understand transition state structure. Systematic analysis of intrinsic
      kinetic isotope effects provides geometric and electronic structure for enzyme
      bound transition states. This information has been used to compare transition
      states for chemical and enzymatic reactions; determine whether enzymatic
      activators alter transition state structure; design transition state inhibitors;
      and provide the basis for predicting the affinity of enzymatic inhibitors.
      Enzymatic transition states provide an understanding of catalysis and permit the
      design of transition state inhibitors. This article reviews transition state
      theory for enzymatic reactions. Selected examples of enzymatic transition states
      are compared to the respective transition state inhibitors.

PMID- 9759502
TI  - The DNA replication fork in eukaryotic cells.
AB  - Replication of the two template strands at eukaryotic cell DNA replication forks
      is a highly coordinated process that ensures accurate and efficient genome
      duplication. Biochemical studies, principally of plasmid DNAs containing the
      Simian Virus 40 origin of DNA replication, and yeast genetic studies have
      uncovered the fundamental mechanisms of replication fork progression. At least
      two different DNA polymerases, a single-stranded DNA-binding protein, a clamp
      loading complex, and a polymerase clamp combine to replicate DNA. Okazaki
      fragment synthesis involves a DNA polymerase-switching mechanism, and maturation
      occurs by the recruitment of specific nucleases, a helicase, and a ligase. The
      process of DNA replication is also coupled to cell-cycle progression and to DNA
      repair to maintain genome integrity.

PMID- 9759503
TI  - TGF-beta signal transduction.
AB  - The transforming growth factor beta (TGF-beta) family of growth factors control
      the development and homeostasis of most tissues in metazoan organisms. Work over
      the past few years has led to the elucidation of a TGF-beta signal transduction
      network. This network involves receptor serine/threonine kinases at the cell
      surface and their substrates, the SMAD proteins, which move into the nucleus,
      where they activate target gene transcription in association with DNA-binding
      partners. Distinct repertoires of receptors, SMAD proteins, and DNA-binding
      partners seemingly underlie, in a cell-specific manner, the multifunctional
      nature of TGF-beta and related factors. Mutations in these pathways are the cause
      of various forms of human cancer and developmental disorders.

PMID- 9759504
TI  - Pathologic conformations of prion proteins.
AB  - While many aspects of prion disease biology are unorthodox, perhaps the most
      fundamental paradox is posed by the coexistence of inherited, sporadic, and
      infectious forms of these diseases. Sensible molecular mechanisms for prion
      propagation must explain all three forms of prion diseases in a manner that is
      compatible with the formidable array of experimental data derived from
      histopathological, biochemical, biophysical, human genetic, and transgenetic
      studies. In this review, we explore prion disease pathogenesis initially from the
      perspective of an autosomal dominant inherited disease. Subsequently, we examine
      how an intrinsically inherited disease could present in sporadic and infectious
      forms. Finally, we explore the phenomenologic constraints on models of prion
      replication with a specific emphasis on biophysical studies of prion protein
      structures.

PMID- 9759505
TI  - The AMP-activated/SNF1 protein kinase subfamily: metabolic sensors of the
      eukaryotic cell?
AB  - Mammalian AMP-activated protein kinase and yeast SNF1 protein kinase are the
      central components of kinase cascades that are highly conserved between animals,
      fungi, and plants. The AMP-activated protein kinase cascade acts as a metabolic
      sensor or "fuel gauge" that monitors cellular AMP and ATP levels because it is
      activated by increases in the AMP:ATP ratio. Once activated, the enzyme switches
      off ATP-consuming anabolic pathways and switches on ATP-producing catabolic
      pathways, such as fatty acid oxidation. The SNF1 complex in yeast is activated in
      response to the stress of glucose deprivation. In this case the intracellular
      signal or signals have not been identified; however, SNF1 activation is
      associated with depletion of ATP and elevation of AMP. The SNF1 complex acts
      primarily by inducing expression of genes required for catabolic pathways that
      generate glucose, probably by triggering phosphorylation of transcription
      factors. SNF1-related protein kinases in higher plants are likely to be involved
      in the response of plant cells to environmental and/or nutritional stress.

PMID- 9759506
TI  - In favor of pediatric neutering.

PMID- 9759507
TI  - An ethicist's commentary on the case of the pregnant dog brought in for a spay
      and found to be pregnant.

PMID- 9759508
TI  - Veterinary medicine in Canada: opportunity for renewal.

PMID- 9759510
TI  - Turbulence in veterinary education.

PMID- 9759509
TI  - Vaccination of dogs and cats: general principles and duration of immunity.

PMID- 9759511
TI  - Atypical sporadic lymphosarcoma in a 7-month-old Holstein heifer.
AB  - A 7-month-old calf with a firm, diffuse infiltration of the left hind limb with
      sciatic nerve motor deficit was presented. The cytology indicated a malignant,
      round cell tumor and at necropsy, tissues were positive to a Kappa-lambda
      immunohistochemistry test. The final diagnosis was sporadic bovine leukosis,
      juvenile form.

PMID- 9759512
TI  - First report of Fasciola hepatica in cattle in Alberta.

PMID- 9759513
TI  - Focal symmetrical encephalomalacia in a 6-month-old Dorset sheep.
AB  - Neurological examination of a sheep that had acute onset of recumbency and mental
      depression indicated a diffuse symmetrical thalamocortical lesion. Cerebrospinal
      fluid analysis suggested a degenerative central nervous system disease. Thiamin
      administration resulted in partial and temporary improvement. Brain histological
      lesions were typical of focal symmetrical encephalomalacia.

PMID- 9759514
TI  - Partial carpal arthrodesis in a calf with chronic infectious arthritis of the
      carpus and osteomyelitis of the carpal and metacarpal bones.
AB  - A calf was treated for chronic infectious arthritis and osteomyelitis of the
      carpus and metacarpus by carpal bone excision, debridement, and cancellous bone
      graft placement in the metacarpal medullary cavity. Following 6 weeks of limb
      immobilization, carpal-metacarpal arthrodesis was achieved. The heifer is pain
      free, and has produced 3 calves.

PMID- 9759515
TI  - Canine coccidiosis.

PMID- 9759516
TI  - Equine osteology: a self-assessment.

PMID- 9759517
TI  - Abnormal interactions of embryonic mouse trisomy 16 heart fibroblasts with
      extracellular matrix components in vitro.
AB  - Trisomy 16 mice have cardiovascular abnormalities thought to arise from altered
      development and maturation of the cardiac cushions. Cell-cell and cell
      extracellular matrix (ECM) interactions play critical roles in heart
      morphogenesis. To begin to examine the potential involvement of cell-ECM
      interactions in abnormal trisomy 16 heart development, fibroblasts were isolated
      from normal and trisomy 16 embryonic mouse hearts. Behavior of these cells was
      compared in bioassays involving cell-ECM interactions including cell attachment
      and collagen gel contraction. Significant differences in cell-ECM interactions
      were found between fibroblasts isolated from normal and trisomy 16 embryonic
      hearts. Trisomy 16 cells attached poorly to collagen and laminin compared to
      normal fibroblasts. Trisomy 16 heart fibroblasts also contracted collagen gels
      less effectively than normal heart fibroblasts. Cell-ECM interactions are largely
      mediated by ECM receptors of the integrin family. Expression of beta 1 integrins
      was examined at the mRNA and protein levels in normal and trisomy 16 fibroblasts.
      Analyses of integrin expression indicated the pattern of integrins produced by
      normal and trisomy 16 fibroblasts to be similar. These results indicate that
      fibroblasts isolated from embryonic trisomy 16 mouse hearts interact with several
      ECM components including collagen and laminin less efficiently than fibroblasts
      from normal mouse embryos. As cell-ECM interactions play significant roles in
      cardiac cushion development, abnormal interactions may contribute to defective
      atrioventricular septal morphogenesis in the trisomy 16 mouse.

PMID- 9759518
TI  - The leukointegrin alpha d/beta 2 (alpha d/CD18): specific changes in surface
      expression in patients on hemodialysis.
AB  - Alpha d/CD18 is a newly discovered leukocyte adhesion molecule with sequence
      homology to CD11a, b and c of the beta 2 integrin family. Little is known about
      alpha d expression in vivo, particularly how it compares with the other beta 2
      integrins. Previous studies have demonstrated that beta 2 integrin expression,
      particularly CD11b, is upregulated in vivo during hemodialysis (HD) with
      complement activating membranes. These changes may contribute to the immunologic
      abnormalities seen in HD patients. Given the well described changes of beta 2
      integrins in these patients, we hypothesized that alpha d expression could also
      be altered by HD. Using flow cytometry with two specific antibodies to alpha d,
      alpha d expression in healthy adults (n = 16) was compared on macrophages (MO) >
      polymorphonuclear cells (PMNs) > lymphocytes (LY). Phorbol ester treatment of
      leukocytes in vitro significantly increased expression on MO and PMN, but not LY.
      Chronic HD patients at baseline (n = 15) had elevated (P < 0.05) alpha d mean
      channel fluorescence (MCF) on MOs, PMNs and LYs compared to normals. PMN alpha d
      MCF increased at 15 min into HD, but then returned to baseline levels at 180 min.
      Alpha d MCF for LYs decreased at 180 min, while MOs levels were unchanged. Alpha
      d expression is increased in chronic renal failure and further regulated by
      hemodialysis, but with unique characteristics compared to the other beta 2
      integrins. Alpha d may be important in abnormal cell-cell contacts in renal
      failure.

PMID- 9759520
TI  - Aggregation independent of N-cadherin and neural cell adhesion molecule on quail
      myoblasts transformed with temperature-sensitive Rous sarcoma virus.
AB  - Quail myoblasts transformed with the temperature-sensitive mutant of Rous sarcoma
      virus (QM-RSV cells) differentiate temperature-sensitively. At 41 degrees C, the
      cells begin to fuse after about 15-18 h and form multinucleated myotubes,
      whereas, at 35.5 degrees C, the cells proliferate. Tyrosine-phosphorylation
      relates to this temperature-sensitive differentiation. In the course of the
      investigation of QM-RSV cells, when QM-RSV cells were dissociated with EDTA and
      shaken in DMEM, the aggregation activity was detected. This activity was
      expressed on the cells cultured at 41 degrees C, but not at 35.5 degrees C. For
      detailed characterization of the aggregation, cells from which cadherin and/or
      neural cell adhesion molecule (NCAM) were removed by trypsin treatment were used.
      It was then observed that temperature-sensitive and calcium-dependent aggregation
      activity was expressed on the cells treated with trypsin and EDTA (TE-cells),
      although the TE-cells did not retain either aggregation molecule. The aggregation
      activity began to be expressed at 2-4 h after temperature shift and increased
      with the differentiation. The expression of the activity related to the tyrosine
      phosphorylation of some protein. The aggregation of TE-cells was completely
      inhibited by D(+)-mannose, D(+)-glucose, and N-acetyl-D-glucosamine, but D(+)
      galactose did not affect the aggregation. Thus, the present results suggest that
      the aggregation of mannose specific C-type animal lectin recognized on TE-cells
      relates to the early stage of the differentiation of QM-RSV cells.

PMID- 9759519
TI  - Engagement of variant CD44 confers resistance to anti-integrin antibody-mediated
      apoptosis in a colon carcinoma cell line.
AB  - The LIM 1863 colon carcinoma cell line grows as structured organoids around a
      central lumen, and we have previously demonstrated that the three-dimensional
      arrangement protects the individual cells from apoptosis induced by an anti-alpha
      v integrin antibody, 23C6 (Bates et al., 1994). Here we show that the
      intercellular forces which drive spheroid formation can be overcome by exposure
      of the cells to a collagen substrate, or more specifically through ligation of
      the CD44 receptor by a monoclonal antibody. Binding to immobilized anti-CD44
      antibody induced a monolayer morphology which is accompanied by fibronectin
      production and secretion, and expression of the integrin alpha v beta 6.
      Significantly, the cells of the monolayer acquired resistance to 23C6 antibody
      mediated apoptosis over time and this property was sustained even after removal
      from the monolayer. We provide data to show that this resistance is not dependent
      on monolayer morphology, constant engagement of the CD44 receptor, loss of the
      23C6 antigen, or elevation of Bcl-2 or Bcl-XL protein. The CD44 expressed by LIM
      1863 is shown to be the metastatic variant of the molecule therefore these
      results provide a possible explanation for the selective advantages conferred by
      expression of this variant for metastasizing colon cancer cells. Overall, the
      findings of this study support a model for the development of malignancy through
      the production of specific survival and growth signals as a direct consequence of
      a signaling event induced by stimulation of an epithelial variant of CD44.

PMID- 9759521
TI  - Cadherin/catenin complexes in murine epidermal keratinocytes: E-cadherin
      complexes containing either beta-catenin or plakoglobin contribute to stable cell
      cell contacts.
AB  - The cadherin/catenin complexes expressed by a murine epidermal keratinocyte cell
      line PDV, expressing E- and P-cadherin, have been analysed using a combination of
      biochemical and confocal microscopy analysis. Two types of E-cadherin complexes,
      containing beta-catenin or plakoglobin and alpha-catenin, were detected in PDV
      cells as in other cell types, while P-cadherin was mainly detected in complexes
      containing beta-catenin and alpha-catenin in PDV and other murine epidermal
      keratinocytes. Biotin-labelling studies have shown that both types of E-cadherin
      complexes are present at the surface of confluent cells. Furthermore, confocal
      microscopy analysis indicated that E-cadherin/plakoglobin complexes are located
      in stable cell-cell contacts at the middle lateral membranes and associated with
      alpha-catenin and the actin cytoskeleton, with a similar distribution to that to
      the E-cadherin/beta-catenin complexes. In addition, E-cadherin/plakoglobin
      complexes not associated with alpha-catenin or the actin cytoskeleton were
      detected in lower planes of the lateral contacting membranes as well as E
      cadherin non-associated with catenins in the more basal planes. These studies
      support that in murine epidermal keratinocytes both beta-catenin- and plakoglobin
      containing E-cadherin complexes contribute to the maintenance of stable cell-cell
      contacts and suggest a differential role of the plakoglobin containing complexes
      in different epithelial cell types.

PMID- 9759522
TI  - Expression of cell adhesion molecules and cytokines in murine antigen-induced
      arthritis.
AB  - Adhesion molecules and cytokines are important in chronic inflammatory conditions
      such as rheumatoid arthritis (RA) by virtue of their role in cell activation and
      emigration. Using immunohistochemical techniques we studied the expression of
      adhesion molecules and cytokines in cryopreserved sections of murine knee joint
      in the course of antigen-induced arthritis, an animal model of human RA. Various
      adhesion molecules and cytokines are expressed in the arthritic joint tissue. LFA
      1, Mac-1, CD44, ICAM-1 and P-selectin were strongly expressed in the acute phase
      and to a lesser degree in the chronic phase of arthritis. VLA-4 and VCAM-1
      appeared to be moderately expressed on day 1, L-selectin between days 1 and 3.
      LFA-1, Mac-1, CD44, alpha 4-integrin, ICAM-1 and the selectins were found
      expressed on cells of the synovial infiltrate, LFA-1, Mac-1 and ICAM-1 on the
      synovial lining layer, and VCAM-1 and P-selectin on endothelial cells. Expression
      of E-selectin could be demonstrated throughout the experiment at a low level in
      cells of the acute cell infiltrate. Cytokines, especially IL-2, IL-4, IL-6, TNF,
      and IFN-gamma, were heavily expressed during the acute phase of arthritis in
      cellular infiltrate. Taken together these data demonstrate that cytokines and
      their activation of adhesion molecules contribute to cell infiltration and
      activation during the initial phase of arthritis and to the induction and
      progression of tissue destruction in arthritic joints. These molecules might be
      potential targets for novel therapeutic strategies in inflammatory and arthritic
      disorders.

PMID- 9759523
TI  - Ad libitum mixing in a taste memory task: methodological issues.
AB  - Ad libitum mixing, an application of the method of adjustment in food research,
      was investigated and evaluated for the purpose of taste memory research. The
      difference between ascending and descending runs in mixing was studied using a
      wide range of prefill concentrations lower and higher than standard. The effect
      of training was studied by comparing subjects with two or 10 replications in the
      first session where a standard was present as a reference. Results showing higher
      reproduced concentrations after a 25 h time interval than those produced
      immediately are consistent with earlier results from within-subject designs.
      Thus, the difference in recall performance did not depend on the design of the
      study. No difference between ascending and descending runs in the mixing was
      observed, thus the prefill concentrations did not affect the reproduction of a
      given standard. There was no significant difference between produced
      concentrations after two and 10 replications, although a non-significant trend
      towards improved performance following 10 replications was observed after the 25
      h time interval.

PMID- 9759524
TI  - Pheromone deactivation catalyzed by receptor molecules: a quantitative kinetic
      model.
AB  - A quantitative model of pheromone-receptor interaction and pheromone
      deactivation, the supposed rate-limiting processes underlying the receptor
      potential kinetics, is worked out for the moth Antheraea polyphemus. In this
      model, the pheromone interacts with the receptor molecule while bound to the
      reduced form of the pheromone binding protein. The receptor molecules--besides
      their receptor function--catalyze the observed shift of the pheromone-binding
      protein from the reduced to the oxidized form (Ziegelberger, G., Eur. J.
      Biochem., 232, 706-711, 1995), which deactivates the pheromone bound to pheromone
      binding protein. With the following parameters, the model fits morphological,
      radiometric, electrophysiological and biochemical data: a maximum estimate of 1.7
      x 10(7) receptor molecules/cell (with 40,000 units/micron 2 of receptor cell
      membrane), rate constants k1 = 0.2/(s.microM) for the association, k2 = 10/s for
      the dissociation of the ternary complex of binding protein, pheromone and
      receptor, and k3 = 10/s for the deactivation via the redox shift. With these
      parameters, the duration of elementary receptor potentials elicited by single
      pheromone molecules (approximately 50 ms) reflects the lifetime of the ternary
      complex, tau = 1/(k2 + k3). The receptor occupancy produced by the model for
      threshold stimuli fits the sensitivity of the receptor cell to single pheromone
      molecules.

PMID- 9759525
TI  - The addition of CO2 to traditional taste solutions alters taste quality.
AB  - Previous studies of the effect of carbonation on taste perception have suggested
      that it may be negligible, manifesting primarily in increases in the perceived
      intensity of weak salt and sour stimuli. Assuming CO2 solutions in the mouth
      stimulate only trigeminal nerve endings, this result is not altogether
      surprising; however, there are neurophysiological data indicating that CO2
      stimulates gustatory as well as trigeminal fibers. In that case, carbonation
      might alter the quality profile of a stimulus without producing substantial
      changes in overall taste intensity--much as occurs when qualitatively different
      taste stimuli are mixed. To address this possibility, subjects were asked to rate
      the total taste intensity of moderate concentrations of stimuli representing each
      of the basic tastes and their binary combinations, with an without added
      carbonation. They then subdivided total taste intensity into the proportions of
      sweetness, saltiness, sourness, bitterness and 'other taste qualities' they
      perceived. The addition of carbonation produced only small increases in ratings
      of total taste intensity. However, rather dramatic alterations in the quality
      profiles of stimuli were observed, particularly for sweet and salty tastes. The
      nature of the interaction is consistent with a direct effect of carbonation/CO2
      on the gustatory system, although the possibility that at least some of the
      observed effects reflect trigeminal-gustatory interactions cannot be ruled out.

PMID- 9759526
TI  - PTC and PROP behave differently in tests of discrimination from their solvents.
AB  - Better discrimination was possible between phenylthiocarbamide (PTC) solutions
      and the pure solvent when the solvent was a tasteless low-concentration NaCl
      solution to which the subject had adapted than when the solvent was purified
      water. The reverse was true for 6-n-propylthiouracil (PROP). The differences in
      discrimination for PROP and PTC in the different solvents were caused by
      differences in the intensity and persistence of aftertastes, rather than a more
      intense perception of the PTC and PROP tastes per se. This has consequences for
      traditional approaches to measuring taste sensitivity, as well as indicating that
      PTC and PROP are not necessarily equivalent indicators of 'taster' versus 'non
      taster' status.

PMID- 9759527
TI  - NaCl-preferring NZB/B1NJ mice and NaCl-avoiding CBA/J mice have similar amiloride
      inhibition of chorda tympani responses to NaCl.
AB  - Integrated chorda tympani nerve responses to NaCl were studied in two mouse
      strains, an NaCl-preferring NZB/B1NJ and an NaCl-avoiding CBA/J. The NaCl
      responses of both strains had similar magnitude and were suppressed by amiloride
      to a similar extent. This suggests that peripheral gustatory responsiveness to
      NaCl is not the only mechanism underlying mouse strain variation in NaCl
      acceptance.

PMID- 9759528
TI  - Influence of physical exercise on human preferences for various taste solutions.
AB  - The effects of physical exercise on preference for various sapid solutions was
      studied in 58 healthy university students. After 30 min of exercise using a
      bicycle ergometer at 50% VO2max (maximal oxygen uptake) intensity, a rating scale
      test on taste hedonic tone and the triangle test for taste absolute threshold
      were done. The test solutions were sucrose, NaCl, citric acid, caffeine and
      monosodium glutamate (MSG). Preference scale values for sucrose and citric acid
      increased after exercise, whereas the values for NaCl, caffeine and MSG were not
      changed. The absolute thresholds for all the sapid solutions did not differ for
      pre- and post-exercise. These findings indicate that in humans preference for
      sucrose and citric acid increase after physical exercise.

PMID- 9759529
TI  - Attentional modulation of central odor processing.
AB  - Two studies were conducted to investigate the influence of attention on the
      components of the chemosensory event-related potential (CSERP). In the first
      study the odors linalool and eugenol were delivered to six male subjects, in the
      second study three male and two female subjects were presented with their own
      body odor (axillary hair) and the body odor of a same sex donor. In both studies
      the odors were presented in an oddball paradigm under ignore and attend
      conditions via a constant-flow olfactometer. In the ignore condition attention
      was diverted from the odors with a distractor task, while in the attend condition
      the subjects were asked to respond to the infrequently occurring odor. In both
      studies the allocation of attention led to a decrease in the latency of the early
      components (N1, P2, N2) and to an increase in the amplitude of the late
      positivities. The modulation of the early components suggests that attentional
      gating in olfaction might already be effective at an early processing level.

PMID- 9759530
TI  - Olfactory memory: the long and short of it.
AB  - It has been proposed that memory for odors does not have a short-term (or
      working) memory system. The distinction between short- and long-term memory in
      other sensory modalities has been generally supported by three main lines of
      evidence: capacity differences between the proposed systems, evidence of
      differential coding, and differential memory losses in neuropsychological
      patients. The present paper examines these issues in an effort to establish a
      similar distinction for the memory of olfactory stimuli. Each of these lines of
      evidence is examined in relation to the literature on olfactory memory. Based on
      this examination, it seems that there is at least preliminary support from each
      of these lines of evidence to advocate a distinction between a long- and short
      term memory for olfactory stimuli. Emphasis is placed upon the qualitative
      similarity of olfactory memory to other memory systems. This similarity is
      further highlighted through an examination of the literature pertinent to serial
      position effects in memory for olfactory stimuli.

PMID- 9759531
TI  - Is there an inner nose?
AB  - Although behavioral and neuropsychological data regarding the existence of images
      for odors are inconclusive, reconsideration of earlier EEG work provides
      reasonably clear evidence for an inner nose. However, further EEG studies and
      neuroimaging data seem essential for conclusive demonstration of an inner nose.

PMID- 9759532
TI  - Theoretical note: tests of synergy in sweetener mixtures.
AB  - Some methods for examining the additivity of sweeteners, and their synergy in
      mixtures depend upon setting component concentrations on the basis of sweetness
      equivalence, usually to a sucrose reference. These methods may under- or over
      predict the sweetness of a mixture, leading to spurious claims of synergy or
      mixture suppression. This paper points out one problem with one such popular
      method, in that the method can lead to a conclusion that a substance would
      synergize with itself. To the extent that self-synergy is an illogical conclusion
      for a mixture comparison, such a method should be avoided in tests of synergy.
      The sweetness equivalence approach is contrasted with a simpler approach based on
      concentrations that does not lead to conclusions of self-synergy.

PMID- 9759534
TI  - Vomeronasal function.
AB  - This contribution briefly explores some unanswered questions about vomeronasal
      organ function, and introduces other contributions from the symposium
      'Vomeronasal Function', presented at the XVII Meeting of the Association for
      Chemoreception Sciences (1996). Key publications appearing since the symposium
      are also listed.

PMID- 9759533
TI  - Bilateral detection thresholds in dextrals and sinistrals reflect the more
      sensitive side of the nose, which is not lateralized.
AB  - Several fundamental questions remain enigmatic concerning human olfactory
      sensitivity, including (i) whether detection threshold differences exist between
      the two sides of the nose (and, if so, whether such differences are influenced by
      handedness) and (ii) whether bilateral (i.e. binasal) stimulation leads to lower
      thresholds than unilateral stimulation (and, if so, whether the degree of
      facilitation is inversely related to general olfactory ability). In this study,
      and well-validated single staircase procedure was used to establish bilateral and
      unilateral detection thresholds for the cranial nerve I stimulant phenyl ethyl
      alcohol in 130 right- and 33 left-handed subjects. No differences in sensitivity
      between the left and right sides of the nose were observed in either group.
      Bilateral thresholds were lower, on average, than unilateral thresholds when the
      latter were categorized in terms of left and right nares. However, the bilateral
      thresholds did not differ significantly from those of the side of the nose with
      the lower threshold. Overall smell ability, as measured by the University of
      Pennsylvania Smell Identification Test, did not interact with any of the test
      measures. These data imply that (i) the left and right sides of the nose do not
      systematically differ in detection threshold sensitivity for either dextrals or
      sinistrals and (ii) if central integration of left:right olfactory threshold
      sensitivity occurs, its effects do not exceed the function of the better side of
      the nose.

PMID- 9759535
TI  - Expression of candidate pheromone receptor genes in vomeronasal neurons.
AB  - In mammals, olfactory sensory perception is mediated by two anatomically and
      functionally distinct organs: the main olfactory epithelium (MOE) and the
      vomeronasal organ (VON). Pheromones activate the VNO and elicit a characteristic
      array of innate reproductive and social behaviors, along with dramatic
      neuroendocrine responses. Recent approaches have provided new insights into the
      molecular biology of sensory transduction in the VNO. Differential screening of
      cDNA libraries constructed from single sensory neurons from the rat VNO has led
      to the isolation of a family of genes which are likely to encode mammalian
      pheromone receptors. The isolation of these receptors from the VNO might permit
      the analysis of the molecular events which translate the bindings of pheromones
      into innate stereotypic behaviors and help to elucidate the logic of pheromone
      perception in mammals.

PMID- 9759536
TI  - Heterogeneity in the accessory olfactory system.
AB  - The mammalian accessory olfactory bulb (AOB) is chemoarchitecturally
      heterogeneous in that it stains differentially with a number of markers; the
      receptor cells that project to the AOB are similarly heterogeneous. What is the
      significance of this heterogeneity? We have found that the AOB of the gray, short
      tailed opossum, Monodelphis domestica, stains differentially with a number of
      'markers': antibodies to olfactory marker protein (OMP) and the alpha subunit of
      the G protein Gi2, the lectin of Vicia villosa and NADPH-diaphorase. These
      markers stain the rostral AOB more strongly than the caudal AOB whereas, the G
      protein subunit G(o) alpha is located predominantly in the posterior subdivision
      of the AOB. This heterogeneity in the chemoarchitecture of the AOB may reflect a
      fundamental organizational dichotomy within the vomeronasal system that
      corresponds to a functional dichotomy. The vomeronasal sensory epithelium also
      exhibits a chemoarchitectural heterogeneity: receptor cells in the basal third
      are G(o) alpha-immunoreactive whereas the cells in the middle third are Gi2 alpha
      immunoreactive. Tracing studies using WGA-HRP demonstrate that the neurons in the
      middle third of the vomeronasal sensory epithelium project their axons to the
      anterior AOB whereas those in the basal third appear to project to the posterior
      AOB.

PMID- 9759537
TI  - Electrophysiological and biochemical responses of mouse vomeronasal receptor
      cells to urine-derived compounds: possible mechanism of action.
AB  - Receptor cells of the vomeronasal organ (VNO) are thought to detect pheromone
      like molecules important for reproductive physiology. Several compounds derived
      from male mouse urine have been demonstrated to affect endocrine events in female
      mice. In the present study, the ability of these compounds to affect VNO activity
      was tested. In dissociated VNO cells held under voltage clamp conditions,
      application of dehydro-exo-brevicomin (DHB) evoked an outward current at negative
      holding potentials and an inward current at positive holding potentials. Under
      current clamp, DHB reduced action potential firing. Since DHB application caused
      a decrease in membrane conductance, this compound appeared to act by reducing
      inward current through closing an ion channel. Biochemical experiments tested the
      effects of DHB and 2-(sec-butyl)-4,5-dihydrothiazole (SBT) on cAMP levels in the
      VNO. A mixture of DHB and SBT decreased cAMP levels in VNO sensory tissue and had
      no effect on VNO non-sensory tissue. The results suggest that pheromones have an
      inhibitory influence on action potential generation and on cAMP levels in
      receptor cells of the VNO.

PMID- 9759538
TI  - Vomeronasal/accessory olfactory system and pheromonal recognition.
AB  - Pregnancy block in mice requires exposure of recently mated females to urinary
      pheromones of a strange male, and when working with inbred strains this
      invariably requires urine from an outbred line. The pheromones which induce
      oestrus and early puberty in mice have been identified as the brevicomins and
      dihydrothiazoles. Since the same vomeronasal, neural and neuroendocrine pathways
      are also activated in pregnancy block, these compounds are likely candidates for
      pregnancy blocking pheromones. However, these relatively simple chemicals lack
      the capacity to code for differing mouse strains. Since large quantities of the
      polymorphic major urinary proteins from the lipocalin family found in urine serve
      as transporters for the dihydrothiazoles and brevicomins, and differ across
      strains, then these proteins must participate in pheromone recognition in the
      context of pregnancy block.

PMID- 9759539
TI  - Construction of Escherichia coli-Streptomyces shuttle expression vectors for gene
      expression in Streptomyces.
AB  - pIJ4123 and pIJ6021 are high-copy-number vectors for gene expression in
      Streptomyces. They contain a strong, thiostrepton-inducible promoter, PtipA. Two
      E. coli-Streptomyces shuttle vectors, pHZ1271 and pHZ1272, were constructed by
      inserting a replicon and bla gene from E. coli into pIJ4123 and pIJ6021,
      respectively. Both vectors were structurally stable either in E. coli or in
      Streptomyces lividans. To demonstrate the utility of pHZ1272, the hemoglobin gene
      of Vitreoscillia (vhb) was cloned into pHZ1272 and expressed in Streptomyces
      lividans. The expression product (VHb) was detected by Western blotting and
      carbon monoxide binding activity analysis.

PMID- 9759540
TI  - Inhibition effect of transgenic tobacco plants expressing snowdrop lectin on the
      population development of Myzus persicae.
AB  - The cDNAs of snowdrop lectin mature protein and its precursor protein, GNA12 and
      GNA34, were inserted downstream of a 35S promoter with a double enhancer and a
      "omega" fragment of TMV-RNA cDNA in the binary vector pBin438, or the phloem
      specific CoYMV promoter in the vector pBcop1, respectively, resulting in the
      construction of four plant expression vectors pBGna12, pBGna34, pBCGna12, and
      pBCGna34. Leaf stripes of Nicotiana tabacum var. K326 were transformed with A.
      tumefaciens LBA4404 harboring the above expression vectors, respectively. PCR and
      Southern blot analysis showed that foreign GNA genes were inserted into the
      genome of transformed tobacco plants. Western blot analysis indicated that GNA
      could be expressed efficiently up to 0.08-0.15% of total soluble proteins in
      transgenic tobacco plants with pBGna34 or pBCGna34, while in those with pBGna12
      and pBCGna12 GNA were hardly detected by immunoassay. The results from insect
      bioassay with a peach aphid (Myzus persicae) demonstrated that the transgenic
      plants of pBGna34 and pBCGna34 were aphid-resistant as shown by a 45-60%
      reduction in insect population density, with some individual transgenic lines
      being reduced by over 90%. In addition, it was evident that the 35S promoter with
      a double enhancer and CoYMV promoter had similar abilities to direct the GNA gene
      to express in transgenic tobacco plants, but because the CoYMV promoter drives
      the foreign gene in a phloem-specific expression manner, the transgenic plants of
      pBCGna34 showed higher aphid resistance.

PMID- 9759541
TI  - Homology modeling of tissue-type plasminogen activator K1 domain and studies on
      the interactions between kringles and lysine.
AB  - The 3-D structure of t-PA K1 domain was predicted by the method of homology
      modeling. The putative lysine-binding pockets of t-PA K1, UK K, PLG K1 and K4
      were determined by superimposing their 3-D structures to that of t-PA K2 domain,
      of which the lysine-binding pockets had been revealed previously. After that the
      key residues of lysine-binding pockets of kringles were identified. The
      structural analyses showed that both the electrostatic potential and hydrophobic
      complementarity were well matched between lysine and the binding pockets of t-PA
      K2, PLG K1 and K4, but for t-PA K1 and UK K domains the complementarity did not
      match well in one or both respects. It is proposed that this is the reason that t
      PA K1 and UK K domains do not bear the ability to bind lysine. With the respect
      of improving the affinity for fibrin, new types of mutants of t-PA K1 and UK K
      domains were designed, and structural changes caused by mutation were predicted
      by simulating the residue replacements. The mutant structural models demonstrated
      that the molecular design was reasonable.

PMID- 9759542
TI  - Molecular cloning of a chitinase gene from Bacillus circulans C-2.
AB  - The 2-10 kb DNA fragments of the PstI partially digested total DNA of Bacillus
      circulans C-2 were cloned into the PstI site of vector pUC19 and the resulting
      hybrid DNA molecules were then transformed into Escherichia coli. One chitinase
      gene-containing clone (named pCHT1) was selected from about 8000 recombinants on
      chitin overlay plates. Analysis of pCHT1 cut with 12 restriction enzymes showed
      that the inserted fragment in this clone was about 3.0 kb in size and contained
      one site for each of the three restriction enzymes: KpnI, SacI, and SspI. Cells
      harboring the recombinants plasmid (pCHT1-R) in which the insert was in an
      inverted orientation also displayed chitinase activity, indicating that the
      cloned fragment from B. circulans C-2 contained an intact chitinase gene and its
      own promoter could be recognized by the Escherichia coli transcriptional system.
      Southern hybridization analysis proved that the inserted fragment of pCHT1 was
      really from the genome of B. circulans C-2, and there was only one copy existing
      in the genome. This fragment could not hybridize with the total DNAs from the
      other seven chitinase-producing bacteria.

PMID- 9759543
TI  - Regulation of callus status and cell-suspending culture in naked seed oat (Avena
      nuda).
AB  - The original calli were obtained by inducing culture of mature embryos of naked
      seed oat on N6 medium. The original calli were white-colored tumor forms, soft
      outside and hard inside. These kinds of calli are easy to differentiate into
      plantlets, and they are not the friable type. Friable embryogenic calli could be
      obtained by cycled regulated culture on IM1-IM4 medium for 7-8 months from the
      original calli. They became vigorous, lightish yellow in color, with small grainy
      forms. Well-separated and fast-growing suspending cell lines have been obtained
      from the above-mentioned embryogenic calli in the liquid medium. Regenerated
      plants have been obtained for this kind of suspension line by culturing on the
      medium for differentiation. The surviving percentage for such plantlets was over
      95% after planting in the soil.

PMID- 9759544
TI  - Selection of EPS-deficient mutants (Exo-) from Rhizobiun huakuii 107 by region
      directed Tn5 mutagenesis.
AB  - pJB-B5 was a recombinant plasmid of pRK415 containing the 5.9 kb B5 fragment from
      exoR'-11. After pJB-B5 was mutagenized by MT614 (mal::Tn5), 10 plasmids TN1-1,
      TN1-12, TN2-2, TN2-3, TN3-1, TN4-1, TN9-1, TN10-1, TN13-1, and TN14-1 with
      different Tn5 insertions in the B5 fragment were constructed. By conjugation of
      TN1-1, etc., into Rhizobium huakuii 107 containing the P-group plasmid pPH1JI
      which is incompatible with pRK415, and simultaneous selection for Rifr (conferred
      by strain 107), Gm(r) (conferred by pPH1JI), and Nmr (retention of Tn5), R.
      huakuii 107 transconjugant yields a strain in which Tn5 has recombined into the
      R. huakuii 107 genome. Three EPS-deficient (Exo-) mutants 107 (TN2-2), 107 (TN10
      1), and 107 (TN13-1) were isolated and their inserted Tn5 was certified as the
      result of a double homologous recombinant event by Southern hybridization
      analysis. This result showed the Tn5 region-directed mutagenesis is an efficient
      way to select Exo- mutant in R. huakuii.

PMID- 9759545
TI  - Batch fermentation and optimization of media for Bacillus thuringiensis.
AB  - The composition of No. II medium obtained with shaking cultivation contained
      three factors: nitrogen source, carbon source, and inorganic salts. The
      relationship between component factors (x(i)) of the media and spore numbers (y)
      of Bacillus thuringiensis (Bt) was demonstrated by the orthogonal-rotation
      combination test. A response surface equation was formed as follows: y = 384 -
      7.245x1 + 11.705x2 + 15.475x3 + 14.039x1(2) + 41.831x2(2) - 79.49x3(2) -
      35.375x1x2 - 3.375x1x3 - 106.625x2x3. The results showed that this method is
      simple, practical, and rapid enough for selecting fermentation media for Bt. In
      addition, the whole course of batch fermentation was also investigated.

PMID- 9759546
TI  - Study on kinetics of ergosterol fermentation.
AB  - The kinetic relationships among the consumption of sucrose, production of
      ergosterol, formation of ethanol, and growth of yeast cells were studied. A two
      stage kinetic model was established. The relative deviations between experimental
      data and simulated results were no more than 20%.

PMID- 9759547
TI  - What is a cystic fibrosis diagnosis?
AB  - Cystic fibrosis (CF) should be considered in patients with a wide variety of
      clinical presentations and of diverse racial and ethnic backgrounds. In most
      cases the diagnosis is suggested by manifestations of chronic sinopulmonary
      disease and exocrine pancreatic insufficiency, and then confirmed by a positive
      sweat test result. Patients may, however, present with pancreatic sufficiency or
      other atypical clinical features, sometimes in association with normal or
      borderline sweat test results. In such cases, the ability to detect CF mutations
      and to measure transepithelial bioelectric properties can be diagnostically
      useful. Mutation analysis can also be used for carrier screening, prenatal
      diagnosis, and newborn screening.

PMID- 9759548
TI  - Clinical implications of cystic fibrosis transmembrane conductance regulator
      mutations.
AB  - Cystic fibrosis (CF) phenotypes are determined by mutations in the CF gene,
      genetic background, and environment. The nature of the cystic fibrosis
      transmembrane conductance regulator (CFTR) mutation determines the extent of
      protein function. CFTR mutations that abolish protein function are associated
      with severe CF phenotypes. Mutants that retain partial function of CFTR are
      associated with mild phenotypes. The effect of CFTR dysfunction is variable in
      different tissues. Atypical phenotypes caused by mutations in the CF gene may be
      revealed by CFTR mutation analysis and family studies. These phenotypes help to
      define the spectrum of clinical manifestations caused by CFTR mutations.

PMID- 9759549
TI  - What we know and what we do not know about cystic fibrosis transmembrane
      conductance regulator.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP
      regulated chloride channel that resides in the apical membrane of many epithelial
      cells. Channel opening requires phosophorylation of serine residues in an
      intracellular regulatory domain by protein kinase A and as the binding and
      hydrolysis of ATP by intracellular nucleotide binding domains. Besides conducting
      the chloride ion, CFTR also regulates the function of other membrane proteins,
      directly or indirectly, notably the outwardly rectifying chloride channel and the
      epithelial sodium channel. The disease cystic fibrosis is caused by mutations in
      CFTR, which can result in defective protein production, defective processing and
      degradation in the endoplasmic reticulum, or defective channel pore properties or
      gating properties.

PMID- 9759550
TI  - Burkholderia cepacia. Management issues and new insights.
AB  - Although Burkholderia cepacia colonizes a relatively small proportion of
      individuals with cystic fibrosis (CF), it is associated with significant
      morbidity and mortality, and has had a profound impact on infection control
      practices. This article reviews the current understanding of the epidemiology of
      B. cepacia infection, describes important recent developments in the microbiology
      and taxonomy of this species, and presents issues that remain obstacles to
      defining the optimal management of B. cepacia infection in CF.

PMID- 9759551
TI  - Basic therapies in cystic fibrosis. Does standard therapy work?
AB  - Epidemiologic data demonstrate a dramatic improvement in survival for cystic
      fibrosis (CF) over the last few decades and projections suggest that trend will
      continue. Standard therapy works and should be aggressively applied to this
      patient population. Although the specific therapies have evolved over the years,
      the basic tenets of CF care remain unchanged and include antibiotics to control
      infection, airway clearance, and adequate nutrition. This article focuses on
      treatment of the pulmonary disease and includes a discussion of the following
      specific components of a standard therapeutic approach to CF: (1) antibiotics,
      (2) airway clearance and exercise, (3) mucolytics, (4) bronchodilators, (5)
      oxygen, (6) anti-inflammatory therapies, and (7) nutritional support. Judicious
      application of these therapies coupled with careful monitoring of pulmonary,
      nutritional, and metabolic parameters results in most CF patients surviving into
      adulthood with an acceptable quality of life.

PMID- 9759552
TI  - Therapies aimed at airway inflammation in cystic fibrosis.
AB  - Therapies aimed at decreasing the inflammatory response present a new strategy
      for treating cystic fibrosis (CF) lung disease. Alternate day prednisone may be
      beneficial, however, unacceptable adverse effects limit long-term use. Inhaled
      corticosteroids are under investigation as a safer alternative. High-dose
      ibuprofen twice daily has been shown to decrease the progression of CF lung
      disease and is without significant toxicity. Other NSAIDs and pentoxifylline and
      fish oil are under consideration. Antiproteases and antioxidants are also being
      studied. The rationale for all of these agents lies in their potential to
      decrease neutrophil influx into the lung, and counteract injurious products of
      neutrophils. Adding anti-inflammatory therapy to an already comprehensive
      treatment program will hopefully decrease morbidity and improve the quality of
      life for patients with CF.

PMID- 9759553
TI  - Therapies directed at the basic defect in cystic fibrosis.
AB  - There are over 600 unique mutations in the cystic fibrosis (CF) gene that can be
      classified in five general categories with respect to specific defect. Through
      basic research into the genetic and physiologic consequences of these mutations,
      it has become possible to design genotype-specific therapeutic strategies. New
      pharmaceutical agents are under development for the rescue of defective cystic
      fibrosis transmembrane conductance regulator mRNA or protein. Some of these
      compounds are undergoing study in CF patients in Phase I clinical trials. This
      article evaluates the current research directed at translating a basic molecular
      understanding of the disease into innovative new treatments.

PMID- 9759554
TI  - Is DNA destiny? A cure for cystic fibrosis.
AB  - Cystic fibrosis (CF) remains an attractive target for cure by gene therapy.
      Results from several trials are reviewed in this article and have shown that
      mature airway epithelial cells are relatively resistant to gene transfer, that
      host immune responses determine the duration of transgene expression and define
      the toxicity, and that the efficiency of transfection remains low. Significant
      hurdles to the development of gene therapy remain, including the definition of
      efficacy endpoints, the ability to produce enough material, and the ability to
      dose the entire lung. Nonetheless, invaluable insights into CF and pulmonary
      biology have been gained in the gene therapy research effort.

PMID- 9759555
TI  - Lung transplantation for cystic fibrosis.
AB  - Lung transplantation currently stands as the only therapeutic option that carries
      the potential to restore patients with advanced cystic fibrosis to a more normal
      state of health. Nonetheless, the procedure carries significant risk and median
      survival following transplantation is only 5 years. This article discusses the
      currently achievable outcomes and the common short-comings of transplantation.
      Strategies to optimize outcomes through appropriate patient selection, use of
      living donors, and novel research initiatives are discussed.

PMID- 9759556
TI  - Osteoporosis in patients with cystic fibrosis.
AB  - Decreased bone density and increased risk of fractures are seen in patients with
      cystic fibrosis. Suboptimal vitamin D levels, nutrition problems, hypogonadism,
      inactivity, corticosteroid use, and cytokines may contribute to the low bone mass
      seen in these patients. Treatment recommendations must be individualized and may
      include nutrition, vitamin D, estrogen or testosterone, and exercise. In high
      risk patients calcitonin or growth hormone could be considered.

PMID- 9759557
TI  - Human Kallikrein 2 (hK2) and prostate-specific antigen (PSA): two closely
      related, but distinct, kallikreins in the prostate.
AB  - Recent studies on human kallikrein 2 (hK2) have revealed striking similarities
      and significant differences with the closely related kallikrein PSA. Both PSA and
      hK2 are primarily localized to the prostate and share close structural
      similarities. Although both kallikreins are produced by the same secretory
      epithelial cells in the prostate, hK2 is associated more with prostate tumors
      than PSA and is highly expressed in poorly differentiated cancer cells. The
      potent trypsin-like activity of hK2 contrasts with the weak chymotrypsin-like
      activity of PSA. The inactive precursor form of PSA, proPSA, is converted rapidly
      to active PSA by hK2, suggesting an important in vivo regulatory function by hK2
      on PSA activity. The high homology between hK2 and PSA results in significant
      cross-reactivity to hK2 by polyclonal and some monoclonal antibodies to PSA.
      Future studies on both PSA and hK2 need to take into account this potential for
      cross-reactivity. Specific monoclonal antibodies to hK2 have now demonstrated
      that serum levels of hK2, like PSA, are correlated with prostate cancer. The
      production of hK2 protein in active protease form and specific monoclonal
      antibodies to the hK2 antigen will allow extensive future studies delineating the
      physiological and clinical utility of this new prostate antigen.

PMID- 9759558
TI  - The radiology of the thoracic manifestations of AIDS.
AB  - The thoracic manifestations of AIDS have undergone a gradual metamorphosis,
      partly due to more awareness about the disease leading to earlier diagnoses and
      partly due to the fact that research has produced more effective prophylaxis as
      well as treatment for these patients. Many patients now demonstrate partial or
      complete clinical response which prolongs the length and quality of life of
      individuals positive for the Human Immunodeficiency Virus (HIV+). Also, with the
      large number of infected individuals coming to medical attention, and the years
      of experience in diagnosing and treating these AIDS patients, we now recognize
      not only the usual but also less usual manifestations of thoracic illnesses in
      AIDS, including infections, non-infectious diseases such as HIV associated
      Lymphocytic Interstitial Pneumonia and the neoplasms associated with AIDS. A
      section will be devoted to HIV infection in children. We will finish the article
      with a discussion of the current role of Nuclear Medicine in the diagnosis of HIV
      associated thoracic diseases. These topics are the subject of this article.

PMID- 9759559
TI  - Tannins and human health: a review.
AB  - Tannins (commonly referred to as tannic acid) are water-soluble polyphenols that
      are present in many plant foods. They have been reported to be responsible for
      decreases in feed intake, growth rate, feed efficiency, net metabolizable energy,
      and protein digestibility in experimental animals. Therefore, foods rich in
      tannins are considered to be of low nutritional value. However, recent findings
      indicate that the major effect of tannins was not due to their inhibition on food
      consumption or digestion but rather the decreased efficiency in converting the
      absorbed nutrients to new body substances. Incidences of certain cancers, such as
      esophageal cancer, have been reported to be related to consumption of tannins
      rich foods such as betel nuts and herbal teas, suggesting that tannins might be
      carcinogenic. However, other reports indicated that the carcinogenic activity of
      tannins might be related to components associated with tannins rather than
      tannins themselves. Interestingly, many reports indicated negative association
      between tea consumption and incidences of cancers. Tea polyphenols and many
      tannin components were suggested to be anticarcinogenic. Many tannin molecules
      have also been shown to reduce the mutagenic activity of a number of mutagens.
      Many carcinogens and/or mutagens produce oxygen-free radicals for interaction
      with cellular macromolecules. The anticarcinogenic and antimutagenic potentials
      of tannins may be related to their antioxidative property, which is important in
      protecting cellular oxidative damage, including lipid peroxidation. The
      generation of superoxide radicals was reported to be inhibited by tannins and
      related compounds. The antimicrobial activities of tannins are well documented.
      The growth of many fungi, yeasts, bacteria, and viruses was inhibited by tannins.
      We have also found that tannic acid and propyl gallate, but not gallic acid, were
      inhibitory to foodborne bacteria, aquatic bacteria, and off-flavor-producing
      microorganisms. Their antimicrobial properties seemed to be associated with the
      hydrolysis of ester linkage between gallic acid and polyols hydrolyzed after
      ripening of many edible fruits. Tannins in these fruits thus serve as a natural
      defense mechanism against microbial infections. The antimicrobial property of
      tannic acid can also be used in food processing to increase the shelf-life of
      certain foods, such as catfish fillets. Tannins have also been reported to exert
      other physiological effects, such as to accelerate blood clotting, reduce blood
      pressure, decrease the serum lipid level, produce liver necrosis, and modulate
      immunoresponses. The dosage and kind of tannins are critical to these effects.
      The aim of this review is to summarize and analyze the vast and sometimes
      conflicting literature on tannins and to provide as accurately as possible the
      needed information for assessment of the overall effects of tannins on human
      health.

PMID- 9759560
TI  - Effective regulatory approval process for food ingredient technologies.
AB  - Most sciences and technologies related to food safety have advanced exponentially
      over the 40 years since passage in the U.S. of the Food Additive Amendment of
      1958 to the Federal Food, Drug and Cosmetic (FD&C) Act. Effective regulatory
      decision making places a high premium on competent professional and
      administrative judgement applied to sound scientific data. This review discusses
      changes and lessons learned in the food safety sciences over the last 4 decades.
      Other segments of the safety and compliance infrastructure necessary to assure
      that the public receives safe and wholesome foods have not kept pace with the new
      scientific knowledge. The quality of foods in our marketplace can be improved
      only after the regulatory and legislative segments of the infrastructure,
      discussed in a companion symposium paper, are brought into better synchrony with
      the sciences.

PMID- 9759561
TI  - An integrated approach to the development of reduced-fat food emulsions.

PMID- 9759562
TI  - [Laser technology in dermatology: quo vadis--science or business?].

PMID- 9759563
TI  - [Value of psychotherapy in expert assessment of skin diseases. Recommendations
      and indications for additional psychotherapy evaluation in expert assessment from
      the viewpoint of dermatology].
AB  - Skin diseases, the psyche and psychological changes are often intertwined,
      especially in patients presenting for expert dermatologic opinion. In many cases
      an additional evaluation provided by psychotherapeutic medicine may be necessary.
      This resource may help with the diagnosis, explanation of the problem and
      estimation of the degree of disability. The different legal guidelines of the
      various evaluation boards must be considered. The role of psychotherapeutic
      evaluation is demonstrated through case examples. The evaluation of new possibly
      occupationally-related disorders such as multiple chemical sensitivity and
      mobbing is considered.

PMID- 9759564
TI  - [Amicrobial intertriginous pustulosis in autoimmune diseases--a new entity?].
AB  - During the last decade an unusual amicrobial intertriginous pustulosis has been
      described in association with autoimmune disease in sixteen female patients. The
      clinical hallmark is a sterile pustular dermatosis preferentially located in
      intertriginous regions that responds to local or systemic corticosteroids.
      Histologic features are subcorneal sometimes spongiform neutrophilic pustules. We
      report an additional patient suffering from this unusual dermatosis. An overview
      of the patients described to date and a review of the literature are given in an
      attempt to delineate this amicrobial intertriginous pustulosis from the known
      pustular dermatoses.

PMID- 9759565
TI  - [Detection of monoclonal T-cells with TCR gamma PCR in mycosis fungoides].
AB  - The monoclonal dominant malignant T cells in mycosis fungoides (MF) carry
      identical TCR gamma rearrangements. Their detection is a useful diagnostic tool.
      Thus, in routine diagnosis we investigated the occurrence of monoclonal T cells
      in skin biopsy samples of MF-patients by TCR gamma-PCR, followed by temperature
      gradient gel electrophoresis (TGGE). In 188 out of 208 MF patients, at least one
      skin sample with sufficient DNA quality for PCR analysis was obtained. Applying a
      consensus PCR for the TCR gamma genes V gamma I and J gamma 1/2, we detected
      monoclonal T cells in 122 cases (65%). In the remaining 66 cases, we performed
      two multiplex-PCRs, covering rearrangements of the other TCR gamma genes. Here we
      found in 11 cases (6%) predominant clonal rearrangements of V gamma II-IV and J
      gamma 1/2 and in 2 (1%) those of V gamma I-IV and J gamma P 1/2. In patients with
      MF, detecting rearrangements of only V gamma I and J gamma 1/2 is sufficient for
      PCR screening analysis. In 53 of the patients (28%) the applied methods revealed
      no monoclonal T cells. This may be due to a low cell number, oligoclonal nature,
      chromosomal abberations or remaining of TCR in germline configuration.

PMID- 9759566
TI  - [Color duplex ultrasound of the finger arteries. An alternative to angiography?].
AB  - By means of modern color-coded duplex sonography (CCDS) even very small vessels
      can be visualized. Maximum resolution nowadays is about 0.5 mm diameter of the
      vessel. We compared the use of CCDS and angiography in studying of acral
      perfusion. Besides morphologic criteria, hemodynamic criteria were recorded.
      Arteries in healthy fingers appear as long and straight vessels with a clearly
      defined border. The physiological maximal blood flow velocity exceeded 20 cm/s.
      CCDS revealed tortuosity of finger arteries as typical finding in thrombangiitis
      obliterans. Segmental stenosis can either be identified morphologically or
      quantified by measurement of the flow velocity with poststenotic maximal systolic
      velocities of less than 20 cm/s or by the acceleration of the blood flow within
      the stenosis, as proven by angiographic examinations. CCDS is suitable for
      evaluation of acral perfusion in patients suffering from secondary Raynaud's
      syndrome. Apart from diagnosis of disturbed acral circulation, other possible
      applications of CCDS are in in the surgical field, for example replantations in
      hand or finger surgery.

PMID- 9759567
TI  - [Edematous swelling of the eyelids caused by contact allergy].
AB  - Cosmetics and ophthalmological topical preparations are the main causes of
      allergic contact eczema about the eye. In most cases, clinical signs are
      conjunctival injection, blepharitis, periorbital dermatitis and edema of lids,
      often combined with itching. Pure edematous swelling of the eyelids should not
      immediately be blamed on a contact allergy, but sufficiently evaluated to exclude
      a benign or malignant process of the eyelids, orbita, lacrimal duct and paranasal
      sinus. We present a patient with pure edematous swelling of the eyelids due to a
      contact allergy by the sympathicomimetic phenylephrine hydrochloride, an uncommon
      allergen.

PMID- 9759568
TI  - [Syringocystadenoma papilliferum and trichoblastoma within a sebaceous nevus].
AB  - Since birth, a 43 year-old man displayed a nevus sebaceus on the right temple.
      The histopathology revealed two distinct adnexal neoplasms associated with this
      lesion: a syringocystadenoma papilliferum and a trichoblastoma. We describe the
      combination of these entities in this report.

PMID- 9759569
TI  - [Sclerosing in multiple familial glomangiomas].
AB  - Glomus tumors (glomangiomata) are benign tumors arising from glomus cells.
      Multiple glomangiomata are less frequent and less painful than the solitary
      variant, which is usually located subungually. Nonetheless multiple glomangiomata
      -sometimes being sensitive to pressure and changes in temperature--may cause
      considerable discomfort. Treatment of multiple glomangiomata is problematic
      because of the often large number of tumors. Sclerotherapy represents an
      alternative to surgical and cryosurgical therapy. We report on sclerotherapy in a
      35 year old female patient with multiple hereditary glomus tumors.

PMID- 9759570
TI  - [Neonatal lupus erythematosus and maternal HELLP syndrome: is there a
      pathogenetic link?].
AB  - A newborn boy developed annular erythematous lesions on his entire body.
      Histopathological examination showed typical features of lupus erythematosus. His
      mother was positive for anti-Ro/SSa and anti-La/SSb antibodies. Neonatal lupus
      erythematosus was diagnosed. During pregnancy the mother had suffered from HELLP
      syndrome. The reported case points out the necessity to differentiate HELLP
      syndrome from first manifestation of lupus erythematosus during pregnancy. A
      direct causal relationship between neonatal lupus erythematosus and HELLP
      syndrome of the mother seems to be unlikely.

PMID- 9759572
TI  - [Isotretinoin in inflammatory bowel diseases].

PMID- 9759571
TI  - [Erythrokeratodermia progressiva symmetrica Darier-Gottron with generalized
      expression].
AB  - A mother and her son presented with erythrokeratodermia progressiva symmetrica
      Darier-Gottron. Both patients developed symmetrical erythematous and
      hyperkeratotic plaques on the extremities and face at the age of 6 months. At the
      age of 2 1/2 years the son suffered from rapid progression of the disease to
      involve the entire skin. The disease of his mother had shown a similar course,
      however, with spontaneous regression at the age of 10 years. The clinical
      features of this generalized condition were identical to congenital lamellar
      ichthyosis. Light microscopy was non-specific with orthohyperkeratosis, focal
      parakeratosis and acanthosis. Electron microscopy revealed numerous keratinosomes
      in the stratum granulosum, keratinosome-derived lamellae in the intercellular
      space and partly augmented keratohyalin with clumping. In the stratum spinosum
      short tonofilament bundles with clumping were remarkable. The child experienced a
      significant and persistent improvement with systemic retinoids. His mother's
      disease was successfully controlled with intermittent retinoid therapy. With the
      clinical and ultrastructural criteria presently available, an unambiguous
      differentiation between erythrokeratodermia progressiva symmetrica, usually a
      localized disorder of keratinization, however with intermittent generalization,
      and other disorders of keratinization seems difficult.

PMID- 9759573
TI  - [Antihistaminics. I].

PMID- 9759574
TI  - Issues in the epidemiology of melanoma.
AB  - Malignant melanoma imposes a considerable public health burden. Both incidence
      and mortality have increased many fold over the past several decades, although
      current trends suggest possible change in the prior patterns. Etiologic factors
      have been established, of which the most important is intense sun exposure.
      Primary prevention and early detection are both potentially critical in reducing
      the burden of melanoma. Much remains to be clarified in our management of this
      disorder on a population basis, and methodologic difficulties are plentiful. The
      potential for substantial reductions in melanoma mortality requires that we
      address the difficulties so that maximally effective public health initiatives
      may be undertaken.

PMID- 9759575
TI  - Clinical recognition of melanoma and its precursors.
AB  - This article reviews the essential clinical features of cutaneous melanoma, as
      well as those of the more common benign pigmented lesions that need to be
      distinguished on clinical examination.

PMID- 9759576
TI  - Pathologic parameters in the diagnosis and prognosis of primary cutaneous
      melanoma.
AB  - Significant progress has been made in the last 10 years on the identification of
      histologic parameters that are independent predictors of melanoma prognosis,
      immunohistochemical markers of cells of melanocytic origin and changes in
      adhesion molecules, cytoskeletal proteins, growth factor receptors, cell
      signaling, and nuclear proliferation proteins associated with tumor progression.
      Histologic criteria may never be completely sufficient to predict behavior
      accurately, because the fundamental change that renders a cell aggressive may not
      be morphologically reflected and may require immunohistochemical or other
      molecular markers to establish behavior. To date, it is humbling that no
      immunohistochemical or molecular marker provides a greater predictable value for
      aggressive behavior than does the simple calibrated ocular micrometer to measure
      tumor thickness. Nevertheless, development of multiple histologic parameters with
      the concept of nontumorigenic RGP and tumorigenic VGP provides a reliable
      statistical model to predict metastases. Fortunately, nontumorigenic RGP
      melanomas with greater than 75% regression are rare. Thus, individual patients
      with melanoma without regression and without the tumorigenic VGP can be given
      reasonable assurance of 100% survival. Nevertheless, this assurance is based on a
      statistical model with a finite population studied. Additional studies are needed
      to confirm this model, as well as more definitive markers to precisely predict
      outcome for those individuals with tumorigenic VGP melanoma.

PMID- 9759577
TI  - Classification and staging of melanoma.
AB  - Although a standardized and uniformly accepted cancer staging system is an
      essential and fundamental requirement to enable meaningful comparisons across
      patient populations, the sometimes capricious biologic behavior of melanoma makes
      developing such a staging system particularly difficult. Since the earliest well
      documented attempts at classifying patients with cutaneous melanoma were
      described more than 50 years ago, the identification of increasingly powerful
      prognostic factors has led to sequential modifications of the cutaneous melanoma
      staging system. The current AJCC staging system is based on relatively well
      established prognostic factors; however, several recent reports have identified
      additional prognostic factors not included in the current system, and other
      studies support the re-evaluation of some of the currently employed staging
      criteria. Some of the more controversial areas include the relevance of level of
      invasion versus tumor thickness, optimal cutoffs for tumor thickness, importance
      of ulceration, the grouping of satellites with in-transit metastases, the
      inclusion of microsatellites and local recurrences as a separate staging
      criterion, the replacement of size of nodal mass with number of positive nodes,
      the importance of nodal metastases in more than one nodal basin, and the
      prognostic significance of distant metastases. Therefore, future modifications of
      the staging system are anticipated to better incorporate these observations.
      Stage-specific staging recommendations for the patient with melanoma provide the
      clinician with a framework to most efficiently assess extent of disease in an era
      of cost-conscious clinical practice. In the asymptomatic patient with primary
      melanoma (stage I or II), we recommend a chest roentgenogram and evaluation of
      alkaline phosphatase and LDH levels; extensive radiologic evaluations are not
      indicated, because the rate of detection in this population is extremely low.
      Additional staging information should also be obtained by the technique of
      lymphatic mapping and sentinel lymphadenectomy. For patients with local-regional
      disease (stage III, satellites, and local recurrence), a selective approach to
      imaging studies is warranted. For this patient population, we recommend complete
      blood count, liver function tests including alkaline phosphatase and LDH, a chest
      roentgenogram, and a CT scan of the abdomen. Although the yield of these tests,
      particularly CT of the abdomen, in detecting distant metastases in asymptomatic
      patients is low, they may identify false-positive abnormalities and provide an
      important baseline for future studies in this high-risk population. For patients
      with disease below the waist or in the head and neck region, we recommend CT of
      the pelvis and CT of the neck, respectively. Additional studies should be done
      only if clinically indicated. Finally, patients with known systemic disease
      (stage IV) should be more comprehensively evaluated, because the likelihood of
      detecting asymptomatic metastases is higher. Accordingly, in addition to the work
      up outlined previously for stage III patients, we also perform a CT scan of the
      chest and MR imaging of the brain; other studies (e.g., bone scan,
      gastrointestinal series) are performed on the basis of symptoms.

PMID- 9759578
TI  - Prognosis in malignant melanoma.
AB  - A uniform and practical classification and staging system for melanoma must exist
      and be widely adopted if useful comparisons between different treatment centers
      and databases are to be made. This article reviews the 1992 American Joint
      Committee on Cancer pTNM staging system. In this classification, localized
      disease without regional nodal involvement is defined as stage I or II, depending
      on the tumor thickness of the primary melanoma. Regional lymph node involvement
      and/or in-transit metastasis is defined as stage III, and systemic metastatic
      disease is defined as stage IV.

PMID- 9759579
TI  - The surgical treatment of primary melanoma.
AB  - Local control is paramount to the clinical management of melanoma. A general
      consensus has been reached regarding the surgical treatment of primary malignant
      melanoma. By means of well-designed, multi-institutional, prospective, and
      randomized trials, the margins of excising the primary melanoma have been reduced
      considerably since the initial guidelines set out by W. S. Handley in 1907. The
      margins of excision now recommended are designed to limit the risk of local
      recurrence with its potential effect on survival and achieve the optimal cosmetic
      outcome. These margins are modified according to particular anatomic site
      constraints.

PMID- 9759580
TI  - Lymphatic mapping and selective lymphadenectomy as an alternative to elective
      lymph node dissection in patients with malignant melanoma.
AB  - This article reviews the use of selective lymphadenectomy, otherwise known as
      sentinel lymph node biopsy, as a clinical alternative in patients with malignant
      melanoma. This represents a compromise between the two traditional treatment
      modalities, elective lymph node dissection or observation of the regional nodal
      basin followed by therapeutic lymph node dissection once disease becomes
      clinically apparent.

PMID- 9759581
TI  - Adjuvant interferon treatment for melanoma.
AB  - After decades of research, the adjuvant therapy of patients with melanoma has
      recently shown significant survival and relapse-free interval benefit for the
      intravenous and subcutaneous administration of maximally tolerable dosages of
      recombinant IFN alpha 2b in a trial conducted by the ECOG (E1684). Despite the
      toxicity of this therapy, retrospective analyses of its impact upon quality-of
      life using Q-TWiST methods and cost-efficacy analyses all argue for the benefit
      and utility of this intervention, especially for node-positive patients with
      resectable melanoma at highest risk of relapse. A confirmatory trial has been
      completed and will mature in the spring of 1998. The impact of lower dosages of
      IFN, apparent transiently during and for a period of time following treatment has
      not been sustained with longer follow-up in a number of trials. Current
      approaches in Europe and North America focus upon refinement of dose and duration
      of treatment with IFN and their potential interactions with, and comparison with,
      active specific immunotherapy with vaccines. A recently emerging area of research
      is the patient with stage IIA melanoma and the potential role of an abbreviated
      high-dose regimen of IFN alpha in this patient subset.

PMID- 9759582
TI  - Vaccines and other adjuvant therapies for melanoma.
AB  - Patients with thick primary melanomas or regional lymph node involvement are at
      high risk of relapse. Investigations of adjuvant therapy over the past 30 years
      show only one significantly positive trial employing high dose interferon-alpha
      2b. This is a potentially toxic regimen, therefore, other better-tolerated forms
      of adjuvant immunotherapy are being studied. Recent advances in basic science
      have led to a better understanding of the T-cell response to human cancer. This
      article discusses the background and current clinical trials of active specific
      immunotherapies for melanoma, including peptide and ganglioside vaccines.

PMID- 9759583
TI  - The evolution of the role of radiation therapy in the management of mucocutaneous
      malignant melanoma.
AB  - The role of radiation therapy in the treatment of malignant melanoma has evolved
      substantially over time. Years ago, malignant melanomas were generally considered
      radioresistant. Over time, the palliative value of radiation therapy was
      established. Most recently it also has become clear that judiciously applied
      therapy may be curative in either an adjuvant setting or for small-volume
      disease.

PMID- 9759585
TI  - Immunotherapy and experimental approaches for metastatic melanoma.
AB  - This article reviews the clinical investigations involving recombinant cytokines
      (either alone or in combination with adoptive immunotherapy, toxicity reduction
      agents, or cytotoxic chemotherapy), vaccines, monoclonal antibodies or antibody
      conjugates, and gene therapy. These various approaches are reviewed for their
      current and potential roles in curing metastatic melanoma.

PMID- 9759584
TI  - Systemic treatment of metastatic melanoma with chemotherapy.
AB  - This article reviews the use of systemic chemotherapy for the treatment of
      metastatic melanoma, including single-agent chemotherapy, combination
      chemotherapy with and without tamoxifen, and biochemotherapy.

PMID- 9759586
TI  - Public health interventions for melanoma. Prevention, early detection, and
      education.
AB  - Worldwide melanoma control programs that include some combination of primary
      prevention, education, and screening activities have only recently begun to
      undergo an evaluation process. More studies with rigorous design and evaluation
      are needed. Until then, the proper public health policy guidelines for melanoma
      control, especially screening, are open to debate. Future studies must determine
      how screening, early detection, case finding, and education can best be used to
      reduce mortality and achieve optimal melanoma control.

PMID- 9759587
TI  - American gastroenterology at the end of the millennium and beyond.

PMID- 9759588
TI  - Preillness non dietary factors and habits in inflammatory bowel disease.
AB  - AIM: Environmental as well as genetic factors play a role in the pathogenesis of
      inflammatory bowel diseases. The effects of smoking and diet have been
      demonstrated. Other factors have not been extensively investigated. PATIENTS:
      Preillness non dietary habits and factors were studied in 88 patients with recent
      onset of inflammatory bowel diseases (55 with ulcerative colitis and 33 with
      Crohn's disease) and in matched 76 population and 68 clinic controls. RESULTS: No
      significant differences were found in relation to education, housing, birth
      weight, breast feeding in infancy and current weight. The current body mass index
      was significantly lower in patients as compared to clinic controls (p < 0.05).
      More patients had low levels of physical activity during the preillness period as
      compared to controls (p < 0.001 vs clinic controls), while more controls engaged
      in moderate (p < 0.05) or high levels of physical activity in the corresponding
      periods. Patients spent fewer hours in strenuous physical activity as compared to
      controls (NS). Patients slept fewer hours per day (p < 0.05 vs clinic controls).
      More patients than controls experienced stressful life events during the year
      prior to onset of symptoms (p < 0.05 for patients with Crohn's disease against
      both controls and all patients vs population controls). CONCLUSIONS: Other
      environmental factors besides smoking and diet may affect the pathogenesis of
      inflammatory bowel disease.

PMID- 9759589
TI  - Stress and physical activity: are they risk factors for IBD?

PMID- 9759590
TI  - Beclomethasone dipropionate (3 mg) enemas combined with oral 5-ASA (2.4 g) in the
      treatment of ulcerative colitis not responsive to oral 5-ASA alone.
AB  - BACKGROUND/AIMS: Beclomethasone dipropionate is one of the topical
      corticosteroids which appear to have minimal systemic effects. We evaluated
      whether combined therapy with Beclomethasone dipropionate enemas and oral 5
      aminosalicylic acid could be effective in patients suffering from ulcerative
      colitis not responsive to oral 5-aminosalicylic acid as monotherapy. PATIENTS: In
      twenty patients, non responders to 5-aminosalicylic acid treatment (2.4-3.6
      g/day) given for at least 6 weeks, Beclomethasone dipropionate enemas (3 mg/60
      ml/day) were added for 4 weeks. METHODS: Efficacy of the combination was
      evaluated before and at the end of the treatment using a clinical, endoscopic and
      histological score. RESULTS: After a four-week treatment period, a significant
      clinical improvement in stool frequency (p < 0.01), stool consistency (p <
      0.001), blood (p < 0.001) and mucus in stools (p < 0.05), was observed. Endoscopy
      and biopsy confirmed an improvement in the activity score at the end of the
      treatment (p < 0.001). Six patients (30%) achieved remission, ten patients showed
      an improvement (50%) and four (20%) showed no benefits. No adverse event was
      observed. CONCLUSIONS: Beclomethasone dipropionate enemas combined with oral 5
      aminosalicylic acid may be a safe and useful therapeutic approach in the
      treatment of ulcerative colitis not responsive to oral 5-aminosalicylic acid
      alone.

PMID- 9759591
TI  - Optimizing strategies in refractory ulcerative colitis.

PMID- 9759592
TI  - Nicotine carbomer enemas--pharmacokinetics of a revised formulation.
AB  - AIMS: Ulcerative colitis is predominantly a disease of non-smokers, and
      transdermal nicotine has therapeutic benefit but causes frequent side-effects. We
      have previously developed a topical enema combining nicotine with a polyacrylic
      carbomer; pharmacokinetic parameters were similar in healthy volunteers and
      patients with active ulcerative colitis. This enema was reformulated to reduce
      and delay nicotine absorption, thereby improving tolerance. METHOD:
      Pharmacokinetic observations and side-effects with both formulations are compared
      in the same 8 healthy volunteers--all non-smokers, 3 male, mean age 33 years. Six
      milligrams of nicotine were complexed with 400 mg of carbomer in a 100 ml liquid
      enema. The original formulation was buffered with potassium/phosphate to pH 5.5,
      kinematic viscosity was 3 mNm; the revised preparation incorporated trometamol 1%
      solution to buffer to pH 4.2, viscosity 5 mNm. All subjects had the two
      formulations on separate occasions at least a month apart, with serial blood
      measurements and side-effect profile recorded for 8 hours. RESULTS: The revised
      enema formulation significantly reduced Cmax for nicotine from 8.3 +/- 2.7 to 6.6
      +/- 2.1, p = 0.03 with some reduction in nicotine absorption and improved
      tolerance. Although there was considerable intersubject variation in profiles for
      nicotine and cotinine, they were similar for each subject on both occasions.
      CONCLUSIONS: The lower pH and greater viscosity reduced the amount of free
      nicotine in its unionised form available for absorption, but made it possible to
      expose colonic mucosa to the same nicotine dose. In other drug formulations where
      side-effects are a limiting factor these modifications may also be relevant.

PMID- 9759593
TI  - Plasma levels of endothelin-1 in patients with Crohn's disease and ulcerative
      colitis.
AB  - AIM: The purpose of this study was to investigate the behavior of circulating
      endothelin-1, a vasoconstrictor and mitogenic peptide, in patients with
      inflammatory bowel disease. PATIENTS: We investigated plasma endothelin-1 levels
      in 29 patients with Crohn's disease, 13 with ulcerative colitis and 26 healthy
      subjects as controls. METHODS: Erythrocyte sedimentation and C-reactive protein
      were also measured in all patients. Plasma endothelin-1 was measured by specific
      radioimmunoassay and expressed as pg/ml. RESULTS: Both Crohn's disease and
      ulcerative colitis patients showed a significant increase in plasma endothelin-1
      concentration (22.3 +/- 8.2 pg/ml and 11.2 +/- 2.7 pg/ml, respectively) when
      compared to healthy subjects (6.2 +/- 1.5 pg/ml). Moreover, plasma endothelin-1
      levels were significantly higher in Crohn's disease patients than those in
      ulcerative colitis patients (22.3 +/- 8.2 pg/ml vs 11.2 +/- 2.7 pg/ml; p < 0.001,
      respectively). A weak correlation (r = 0.645; p < 0.013) between erythrocyte
      sedimentation and endothelin-1 levels was observed in Crohn's disease patients.
      Age, sex, clinical activity of the disease, duration of history, anatomical
      localization of disease and therapy had no influence on plasma endothelin-1
      levels. CONCLUSION: Our results show that plasma endothelin-1 levels increase in
      chronic inflammatory bowel disease and mainly in Crohn's disease. This
      observation leads us on to believe that endothelin-1 has a important role in
      inflammatory bowel disease.

PMID- 9759594
TI  - Use of the stable isotope 65Cu test for the screening of Wilson's disease in a
      family with two affected members.
AB  - BACKGROUND/AIMS: An improved method for the study of copper metabolism in
      Wilson's disease, using a stable, rather than radioactive, copper isotope (65Cu)
      has recently been described. We report on the use of this method for the study of
      a family with two members affected by Wilson's disease. SUBJECTS: The family
      comprised parents and four siblings: one 20-year-old male and three females, aged
      22, 17 and 5 years, respectively. The boy and the 17-year-old girl both presented
      with liver cirrhosis. Diagnosis of Wilson's disease was suggested by elevated
      liver copper content and/or low caeruloplasmin levels and Kayser-Fleischer ring.
      METHODS: All family members were given an oral dose of 3 mg of 65Cu. Blood
      samples were taken at 0, 1, 2, 6, 24, 48, and 72 hours. In 4 subjects, additional
      blood samples were drawn at 7, 14 and 21 days after dosage. The ratio 65Cu:63Cu
      in serum was determined in all samples by means of Inductively Coupled Plasma
      Mass Spectrometry. RESULTS: The diagnosis of Wilson's disease was confirmed in
      the two symptomatic members by the unequivocal decrease observed in the 65Cu
      percent enrichment, which approached zero by 72 hours. In contrast, Wilson's
      disease could be definitely excluded in both siblings, one of whom only 5 years
      old, on the evidence of net secondary peaks, showing normal incorporation of 65Cu
      into caeruloplasmin. These findings were later confirmed by genetic analysis.
      Parents, who carried defective genes with different mutations, also showed
      different abnormalities of copper metabolism. CONCLUSIONS: The oral test with the
      stable copper isotope 65Cu is a safe, non invasive option able to exclude
      Wilson's disease in patients with a difficult diagnosis or in a presymptomatic
      stage. However, positive tests must still be confirmed by copper dosage in liver
      biopsies, as heterozygotes can present with severe alterations of copper
      metabolism, without developing symptoms of the disease. The use of this test in
      conjunction with genetic analysis on a larger number of heterozygous subjects may
      add to the understanding of the Wilson's disease defect.

PMID- 9759595
TI  - Updating prognosis of cirrhosis by Cox's regression model using Child-Pugh score
      and aminopyrine breath test as time-dependent covariates.
AB  - BACKGROUND AND AIMS: The determination of aminopyrine breath test on entry into
      the study was recently shown to improve the accuracy of prediction of death based
      on the Child-Pugh classification, but the possible usefulness of serial
      determinations of both parameters has not been assessed. In the present study, we
      aimed at evaluating whether serial determinations of aminopyrine breath test and
      Child-Pugh score improve prognostic accuracy in patients with cirrhosis, compared
      with determinations obtained only on admission. PATIENTS: In 74 patients with
      liver cirrhosis aminopyrine breath test and Child-Pugh score were obtained upon
      entry into the study. Patients were followed with sequential aminopyrine breath
      tests and assessments of the Child-Pugh score every 4-6 months. A total number of
      232 determinations were obtained. During follow-up 45 patients died, on average
      after 12 months of follow-up. RESULTS: Child-Pugh score improved in the beginning
      of follow-up, and then remained fairly constant; aminopyrine breath test showed
      no improvement in the beginning of follow-up, but rather a slowly progressive
      decline. In patients who died, both the Child-Pugh score and the metabolism of
      aminopyrine were significantly more impaired in the last year preceding death (p
      < 0.05). Applying Cox's regression model with time-dependent covariates, Child
      Pugh score and aminopyrine breath test were independent significant predictors of
      survival. The model with time-dependent covariates explained the observed
      survival much better than the model with time-fixed covariates (chi-sq. explained
      by regression = 31.45 vs 11.97; d.f. = 2; p = 0.0000001 vs 0.003). CONCLUSIONS:
      These data suggest that serial determinations of Child-Pugh score and aminopyrine
      breath test can be used to efficiently update prognosis of cirrhosis.

PMID- 9759596
TI  - Does repetition of quantitative liver function tests improve prognosis accuracy
      of patients with chronic liver disease?

PMID- 9759597
TI  - Need and supply of liver grafts in Tuscany.
AB  - BACKGROUND: Epidemiological data are fundamental to adequately plan the activity
      of a liver transplantation centre. AIM: To evaluate the ratio between need and
      supply of liver grafts in Tuscany and to develop a regional strategy aimed at
      increasing donor recruitment. METHODS: The need for liver grafts was estimated on
      the basis of an epidemiological study: 19 Medical Units were requested to fill in
      a questionnaire inquiring into all Tuscan patients evaluated for liver disease
      during three different periods of one month each in 1996. The information
      collected was matched with the selection criteria currently employed at our
      centre and the patients were classified into the following four categories: 1.
      current transplantation candidates; 2. future transplantation candidates; 3.
      candidates not suitable on account of age; 4. candidates not suitable on account
      of exclusion criteria. The number of liver donors was obtained from the donor
      registry. RESULTS: Questionnaires were returned for a total of 452 patients: 27
      (5.97%) were classified as current transplantation candidates, 62 (13.72%) as
      future transplantation candidates and 19 (4.20%) as candidates not suitable on
      account of age. The annual incidence and prevalence of transplantation candidates
      were 14.7 and 30.6 cases per million inhabitants, respectively. If age (> or = 61
      years) was not considered in the exclusion criteria, the annual prevalence of
      transplantation candidates reached 52.1 cases per million inhabitants. During the
      same period there were 44 organ donors (12.2 donors per million inhabitants) of
      whom 33 were suitable for liver donation (9.3 liver donors per million
      inhabitants). To reduce this discrepancy a new programme for organ recruitment,
      based upon the Spanish model, has been recently employed. CONCLUSIONS: The annual
      need for liver grafts in Tuscany largely exceeds the number of donors currently
      available. It is hoped that the new regional programme for organ recruitment will
      improve these figures.

PMID- 9759598
TI  - Serum interleukin 6 in the prognosis of acute biliary pancreatitis.
AB  - BACKGROUND: Data concerning the interleukin 6 pattern in acute biliary
      pancreatitis are lacking. AIM: To define the best cut-off point of this molecule
      in differentiating the severe form of acute biliary pancreatitis from the mild
      form and to evaluate its sensitivity, specificity and diagnostic accuracy in the
      prognosis of acute biliary pancreatitis in comparison with those of serum C
      reactive protein. PATIENTS: Forty-four patients with acute biliary pancreatitis:
      27 patients with mild pancreatitis and 17 with the severe form of the disease.
      METHODS: Serum interleukin-6 and C-reactive protein concentrations were assessed
      in all patients on admission and for the following 5 days. RESULTS: Serum
      interleukin-6 levels were significantly higher (p < 0.02) in patients with severe
      acute biliary pancreatitis than in those with the mild form of the disease. No
      significant difference in serum C-reactive protein levels was found in the first
      2 days in patients with mild biliary pancreatitis when compared to those with the
      severe form of the disease. Using a cut-off point of 2.7 pg/ml for serum
      interleukin-6 and 11 mg/dl for serum C-reactive protein, the sensitivity of the
      two molecules in assessing the severity of acute pancreatitis on the first day of
      the study was 87.5% for interleukin-6 and 6.3% for C-reactive protein, the
      specificity, 83.3% for interleukin-6 and 91.7% for C-reactive protein, and the
      accuracy 85.0% for interleukin-6 and 57.5% for C-reactive protein. CONCLUSIONS:
      Serum determination of interleukin-6 in the first 24 hours of the disease is a
      better marker of the severity of acute biliary pancreatitis than C-reactive
      protein.

PMID- 9759599
TI  - Early parameters of prognosis in acute pancreatitis--can cytokine measurements
      fulfil their promise?

PMID- 9759600
TI  - Endoscopic retrograde cholangiopancreatography in patients with Billroth II
      gastrectomy.
AB  - AIM: Endoscopic retrograde cholangiopacreatography and associated therapeutic
      procedures are widely used in routine clinical practice. The changes in the upper
      gastrointestinal anatomy after a Billroth II anastomosis may present technical
      difficulties at endoscopic retrograde cholangiopacreatography. METHODS AND
      PATIENTS: The case records of all patients who underwent endoscopic retrograde
      cholangiopacreatography at our Unit from January 1985 to December 1995 were
      reviewed. All patients who had had a previous Billroth II anastomosis or
      gastroenteroanastomosis were included in this analysis. Of the 5994 procedures
      performed, 124 patients with Billroth II surgery and 10 with a
      gastroenteroanastomosis were identified. RESULTS: In these patients, the papilla
      was located in 89% of cases from 1985 to 1990 and in 100% of cases from 1991 to
      1995. Overall, the success rates for pancreatography, cholangiography, and
      endoscopic sphincterotomy were 94%, 97.7%, and 100%, respectively. The morbidity
      and mortality rates were 7.4% and 0%, respectively. CONCLUSIONS: The success rate
      for endoscopic retrograde cholangiopacreatography in patients with Billroth II
      gastrectomy is similar to that of a normal population.

PMID- 9759601
TI  - Endoscopic pancreaticobiliary procedures in patients with a Billroth II
      resection: a 10-year follow-up study.
AB  - BACKGROUND: Previous gastrectomy may present technical difficulties for the
      endoscopist, but the problem appears to be decreasing. AIM: To assess endoscopic
      retrograde cholangiopancreatography and endoscopic papillotomy in Billroth II
      patients compared to similar material acquired 10 years ago. MATERIAL AND
      METHODS: We compared a five-year series of patients submitted to Billroth II to a
      similar series at our two hospitals obtained 10 years ago. The techniques applied
      were mostly unchanged, although stent-assisted needle knife papillotomy was
      successfully introduced during the last year. RESULTS: Endoscopic retrograde
      cholangiopancreatography was successful in 123 out of 138 patients (89%),
      requiring a total of 206 procedures to complete diagnostic and therapeutic goals.
      Endoscopic papillotomy was successful in 81 out of 87 cases (93%). Additional
      procedures were performed in 40 of the patients. Two duodenal perforations
      occurred. Compared to ten years ago, total numbers were almost unchanged, but the
      proportion of patients with a therapeutic indication increased from 34% to 63%.
      CONCLUSION: There is still need for the special endoscopic retrograde
      cholangiopancreatography competence that Billroth II anatomy requires, and the
      special techniques described here should be available in at least some referral
      endoscopy centres.

PMID- 9759602
TI  - ERCP and endoscopic sphincterotomy in Billroth II patients: a demanding technique
      for experts only?

PMID- 9759603
TI  - Flutamide-induced acute hepatitis: investigation on the role of immunoallergic
      mechanisms.
AB  - Flutamide is a nonsteroidal antiandrogen drug used in the treatment of prostatic
      cancer. Hepatotoxic reactions due to flutamide have been reported with an
      incidence ranging from 1% to 5%. These reactions are usually reversible upon
      withdrawal of the drug but can occasionally be life-threatening. The mechanism of
      flutamide-associated hepatotoxicity is not well established. We report a case of
      a 69-year-old man with prostatic carcinoma in whom flutamide induced an acute
      hepatitis which resolved completely soon after drug withdrawal. In this patient,
      we have studied the possible involvement of an immunological mechanism in causing
      flutamide hepatitis by investigating the presence of circulating antibodies
      directed against reactive metabolites of flutamide bound to liver proteins with
      enzyme-linked immunosorbent assay technique. Although, in the present case, we
      have failed to detect IgG reacting with rat liver microsomes incubated in vitro
      with flutamide, this does not completely rule out the possibility of an
      immunological involvement in flutamide hepatotoxicity. The possibility of severe
      flutamide-related injury, independently of the underlying pathogenic mechanism,
      strongly suggests the need for careful monitoring of liver enzymes in patients
      taking this drug.

PMID- 9759604
TI  - Ritodrine-related liver injury. Case reports and review of the literature.
AB  - beta-sympathicomimetic ritodrine chloridrate is a commonly used tocolytic agent
      for the treatment of preterm labour. Previous reports have described the
      occurrence of liver test abnormalities during ritodrine administration but the
      clinical significance and incidence of this side effect are still unclear. We
      report on two cases including one with a positive rechallenge of liver injury
      during oral ritodrine administration and a review of the literature.

PMID- 9759605
TI  - The case for case reports.

PMID- 9759606
TI  - Haemodynamics and fluid retention in liver disease.
AB  - Patients with cirrhosis and portal hypertension exhibit characteristic
      haemodynamic changes with a hyperkinetic systemic circulation, an abnormal
      distribution of the blood volume and neurohumoral dysregulation. Their plasma and
      noncentral blood volumes are increased, but the central and arterial blood volume
      and systemic vascular resistance are decreased. A systemic and splanchnic
      vasodilatation is of pathogenic importance to the low systemic vascular
      resistance and abnormal volume distribution. These are important elements in the
      development of the low arterial blood pressure and hyperkinetic circulation in
      cirrhosis. Various vasodilators such as nitric oxide, calcitonin gene-related
      peptide, and adrenomedullin are among potential candidates in the vasodilatation
      in cirrhosis. Besides reflex induced enhanced sympathetic nervous activity,
      activation of the renin-angiotensin-aldosterone system, and elevated circulation
      vasopressin, endothelin-1 may also be implicated in the haemodynamic counter
      regulation in cirrhosis. Recent research has focused on the assertion that the
      haemodynamic and neurohumoral abnormalities in cirrhosis are part of a general
      circulatory dysfunction, influencing the course of the disease with reduction of
      kidney function and sodium-water retention as the outcome.

PMID- 9759607
TI  - "Breakthrough" during interferon therapy for chronic hepatitis C. Overview on the
      diagnosis, possible aetiology and recommendations for management.
AB  - A relapse of serum aminotransferase levels after complete normalisation during
      alpha interferon therapy for chronic hepatitis C is diagnosed as Breakthrough.
      Its prevalence ranges between 14% and 21% of the responders, with no significant
      differences between the alpha interferons. Hepatitis C virus genotype and
      interferon dose do not seem to represent predisposing factors. The development of
      neutralising antibodies to interferon is associated with Breakthrough in about
      half of the patients; other aetiologic factors such as down-regulation of
      interferon receptors or development of virus resistance to interferon may be
      implicated in the remaining cases. The therapeutic switch from recombinant to
      lymphoblastoid alpha interferon has been demonstrated to be a successful strategy
      to overcome Breakthrough and to restore a complete response.

PMID- 9759608
TI  - Current concept of the role of monocytes/macrophages in inflammatory bowel
      disease--balance of proinflammatory and immunosuppressive mediators.
AB  - Macrophages are important in providing the first line of intestinal defence
      against microorganisms or toxins that break the epithelial barrier, by presenting
      antigen to sensitised T cells and releasing a variety of cytokines and
      inflammatory mediators. During active states in inflammatory bowel disease, large
      numbers of monocytes leave the bloodstream and migrate into the inflamed mucosa
      and submucosa. Phenotypic studies have previously shown the presence of much more
      marked macrophage heterogeneity in inflammatory bowel disease mucosa than in
      normal mucosa. In both Crohn's disease and in ulcerative colitis, distinct
      macrophage populations have been found, being prominent in active disease, but
      absent from normal mucosa. Studies in our institution have shown that the Ca(2+)
      binding proteins MRP8 and MRP14 as well as their heterocomplex MRP8/14 (27E10
      epitope) are expressed in the majority of granulocytes and macrophages in active
      but not inactive inflammatory bowel disease. Furthermore, a strong complex
      MRP8/14 immunoreactivity was present in epithelial cells of the terminal ileum
      adjacent to ulcerative and fissuring lesions, while epithelial cells of large
      bowel tissues were consistently negative. In vitro studies revealed that
      interleukin-13, interleukin-10 and interleukin-4 strongly suppress secretion of
      different monocytic proteins. A combination of TH2-cytokines even at suboptimal
      concentrations significantly suppressed protein secretion, much more than using
      interleukin-13, interleukin-10 or interleukin-4 at a double concentration alone.
      Our morphological findings demonstrate the presence of MRP8/14 (27E10 antigen)
      both in monocytes/macrophages and in epithelial cells in active inflammatory
      bowel disease. Systemic or topical application of combined cytokine treatment
      might be a new effective therapeutic approach for chronic inflammatory bowel
      disease especially in those cases in which monocytes/macrophages lose their
      ability to respond, to some degree, to anti-inflammatory cytokines.

PMID- 9759609
TI  - The emerging impact of phage display technology in thrombosis and haemostasis.

PMID- 9759610
TI  - The prothrombin 20210A allele is the most prevalent genetic risk factor for
      venous thromboembolism in the Spanish population.
AB  - We investigated the prevalence of the new recently reported mutation in the
      prothrombin gene (20210 A) in a sample of 116 unrelated patients with venous
      thromboembolism. We found 20 heterozygous carriers (17.2%, CI 95% 10.4-21.1). In
      comparison, we observed 13 carriers among 201 healthy unmatched controls (6.5%,
      CI 3.5-10.8). The 20210 A mutation seems to increase the risk of venous
      thrombosis 3-fold (odds ratio 3.1, 95% CI 1.4-6.6). Considering only patients
      with a first event (n = 62) the OR was 2.0 (p = 0.18, NS) while those with
      recurrent events (n = 54) showed an OR of 5.9 (95% CI 2.5-14.4). A majority of
      heterozygous patients (55%) presented a second thrombophilic factor and 60% of
      affected females had their first event before 30 years of age, while on oral
      contraceptive treatment. The prevalence found in this study for healthy people is
      the highest reported to date. The 20210 A variant appears to be the most
      prevalent genetic risk factor among patients with thrombosis in our geographical
      area.

PMID- 9759611
TI  - Treatment with a GPIIb/IIIa antagonist inhibits thrombin generation in platelet
      rich plasma from patients.
AB  - Infusion of the GPIIb/IIIa-inhibitor MK383 inhibits thrombin generation in
      platelet rich plasma by interfering with the production of platelet procoagulant
      phospholipid exposure. The effect is similar to that of 0.2 U/ml of heparin.
      Heparin infusion, well known to inhibit thrombin generation by fostering
      antithrombin activity, inhibits the formation of platelet-derived procoagulant
      microparticles, probably by decreasing the formation of free thrombin, which,
      under our circumstances, is the main platelet activator.

PMID- 9759612
TI  - A mutation in plasma platelet-activating factor acetylhydrolase (Val279Phe) is a
      genetic risk factor for cerebral hemorrhage but not for hypertension.
AB  - Platelet-activating factor (PAF) acetylhydrolase is an enzyme that inactivates
      PAF. Deficiency of this enzyme is caused by a missense mutation in the gene. We
      previously found a higher prevalence of this mutation in patients with ischemic
      stroke. This fact suggests that the mutation might enhance the risk for stroke
      through its association with hypertension. We have addressed this hypothesis by
      analyzing the prevalence of the mutation in hypertension. We studied 138 patients
      with essential hypertension, 99 patients with brain hemorrhage, and 270 healthy
      controls. Genomic DNA was analyzed for the mutant allele by the polymerase-chain
      reaction. The prevalence of the mutation was 29.3% (27.4% heterozygotes and 1.9%
      homozygotes) in controls and 36.2% in hypertensives and the difference was not
      significant. The prevalence in patients with brain hemorrhage was significantly
      higher than the control: 32.6% heterozygotes and 6.1% homozygotes (p <0.05). PAF
      acetylhydrolase deficiency may be a genetic risk factor for vascular diseases.

PMID- 9759613
TI  - The molecular basis of antithrombin deficiency in Belgian and Dutch families.
AB  - The molecular basis of hereditary antithrombin (AT) deficiency has been
      investigated in ten Belgian and three Dutch unrelated kindreds. Eleven of these
      families had a quantitative or type I AT deficiency, with a history of major
      venous thromboembolic events in different affected members. In the other two
      families a qualitative or type II AT deficiency was occasionally diagnosed. DNA
      studies of the AT gene were performed, using polymerase chain reaction single
      strand conformation polymorphism (PCR-SSCP) analysis, followed by direct
      sequencing of the seven exons and intron-exon junction regions. Six novel point
      mutations were identified: four missense, one nonsense mutation and a single
      nucleotide deletion near the reactive site, causing a frameshift with premature
      translation termination. In two kindreds the underlying genetic defect was caused
      by a whole gene deletion, known as a rare cause of AT deficiency. In these cases,
      Southern blot and polymorphism analysis of different parts of the AT gene proved
      useful for diagnosis. In another kindred a partial gene deletion spanning 698
      basepairs could precisely be determined to a part of intron 3B and exon 4. In two
      type I and in both type II AT deficient families a previously reported mutation
      was identified. In all cases, the affected individuals were heterozygous for the
      genetic defect.

PMID- 9759614
TI  - Hemostatic effects of oral contraceptives in women who developed deep-vein
      thrombosis while using oral contraceptives.
AB  - OBJECTIVE: Comparison of the effect of oral contraceptives on hemostatic
      variables in venous thrombosis patients (thrombosis while using oral
      contraceptives) with the effect in healthy control subjects. Our aim was to
      assess whether some of these effects were more pronounced in women who had
      suffered thrombosis, i.e., whether these were "hemostatic hyperresponders". STUDY
      DESIGN: A population-based case-control study, the Leiden Thrombophilia Study.
      MATERIALS AND METHODS: We investigated 99 pre-menopausal women, age 15-49 years,
      who had used oral contraceptives at the time of a first, objectively confirmed
      episode of deep-vein thrombosis. They were not pregnant, nor in puerperium, nor
      had had a recent miscarriage, and were not using injectable progestogens, nor
      suffering from inherited coagulation defects. The median time between occurrence
      of deep-vein thrombosis and venepuncture was 18 months, and 30 of the 99 women
      were still using oral contraceptives, while 69 had discontinued oral
      contraceptive use. In addition, a group of 153 control women (54 of them were
      oral contraceptive users and 99 were non-users) were studied. The following
      hemostatic variables were measured: APTT, factor VII, factor VIII, factor XII,
      fibrinogen, prothrombin, total antithrombin, normalised activated protein C
      sensitivity ratio (n-APC-sr), protein C, protein S and free protein S. RESULTS:
      We found marked and significant effects of oral contraceptive use on the levels
      of several clotting factors, with an increase in factor VII, factor XII, protein
      C and a decrease in antithrombin, n-APC-sr and protein S. Less marked effects
      that were non-significant or only significant in either patients or controls,
      were an increase in factor VIII, fibrinogen and prothrombin and a decrease in the
      APTT and free protein S. In the former thrombosis patients several of these
      effects of oral contraceptives were more pronounced than in healthy women:
      specifically on factor VII, antithrombin, n-APC-sr and protein C. CONCLUSIONS:
      Our results of the effects of oral contraceptives generally confirm previous
      reports in healthy volunteers. Our data also show that in former deep-vein
      thrombosis patients these effects are more pronounced. Apparently some women
      become "high hemostatic responders" when exposed to oral contraceptives, and they
      may be the women most vulnerable to its thrombogenic effects.

PMID- 9759616
TI  - Heterogeneity and immunochemical properties of anti-beta2-glycoprotein I
      autoantibodies.
AB  - Most anticardiolipin antibodies (ACA) associated with antiphospholipid syndrome
      (APS) are directed against epitopes expressed on beta2-glycoprotein I (beta2GPI).
      Despite a good correlation between standard ACA assays and those using purified
      human beta2GPI as the sole antigen, some sera from APS patients only react in the
      latter. This is indicative of heterogeneity in anti-beta2GPI antibodies. To
      characterize their reactivity profiles, human and bovine beta2GPI were
      immobilized on gamma-irradiated plates (beta2GPI-ELISA), plain polystyrene
      precoated with increasing cardiolipin concentrations (CL/beta2GPI-ELISA), and
      affinity columns. Fluid-phase inhibition experiments were also carried out with
      both proteins. Of 56 selected sera, restricted recognition of bovine or human
      beta2GPI occurred respectively in 10/29 IgA-positive and 9/22 IgM-positive
      samples, and most of the latter (8/9) were missed by the standard ACA assay, as
      expected from a previous study. Based on species specificity and ACA results, IgG
      positive samples (53/56) were categorized into three groups: antibodies reactive
      to bovine beta2GPI only (group I) or to bovine and human beta2GPI, group II being
      ACA-negative, and group III being ACA-positive. The most important group, group
      III (n = 33) was characterized by (i) binding when beta2GPI was immobilized on
      gamma-irradiated polystyrene or cardiolipin at sufficient concentration
      (regardless of beta2GPI density, as assessed using 125I-beta2GPI); (ii) and low
      avidity binding to fluid-phase beta2GPI (Kd in the range 10(-5) M). In contrast,
      all six group II samples showed (i) ability to bind human and bovine beta2GPI
      immobilized on non-irradiated plates; (ii) concentration-dependent blockade of
      binding by cardiolipin, suggesting epitope location in the vicinity of the
      phospholipid binding site on native beta2GPI; (iii) and relative avidities
      approximately 100-fold higher than in group III. Group I patients were
      heterogeneous with respect to CL/beta2GPI-ELISA and ACA results (6/14 scored
      negative), possibly reflecting antibody differences in terms of avidity and
      epitope specificity. Affinity fractionation of 23 sera showed the existence, in
      individual patients, of various combinations of antibody subsets solely reactive
      to human or bovine beta2GPI, together with cross-species reactive subsets present
      in all samples with dual reactivity namely groups III and II, although the latter
      antibodies were poorly purified on either column. Therefore, the mode of
      presentation of beta2GPI greatly influences its recognition by anti-beta2GPI
      antibodies with marked inter-individual heterogeneity, in relation to ACA
      quantitation and, possibly, disease presentation and pathogenesis.

PMID- 9759615
TI  - Effect of cilostazol on soluble adhesion molecules and platelet-derived
      microparticles in patients with diabetes.
AB  - We evaluated the plasma concentrations of soluble adhesion molecules and platelet
      derived microparticles (PMP) in patients with non-insulin dependent diabetes
      mellitus (NIDDM) and studied the effect of cilostazol on PMP generation. There
      were differences in the levels of soluble adhesion molecules between NIDDM
      patients (N = 43) and the control subjects (N = 30) (soluble thrombomodulin:
      11.5+/-5.3 vs. 7.0+/-1.2 TU/ml, p<0.0001; soluble vascular cell adhesion molecule
      1: 708+/-203 vs. 492+/-113 ng/dl, p<0.0001; soluble intercellular cell adhesion
      molecules- 1: 274+/-65 vs. 206+/-48 ng/dl, p<0.0001; soluble P-selectin: 194+/-85
      vs. 125+/-43 ng/dl, p<0.0001). There were also differences in the levels of PMP
      and platelet activation markers between NIDDM patients and the controls (PMP:
      943+/-504 vs. 488+/-219/10(4) plt, p<0.0001; platelet CD62P: 9.2+/-4.6 vs. 4.4+/
      4.3%, p<0.001; platelet CD63: 10.2+/-4.5 vs. 4.5+/-3.3%, p<0.0001; platelet
      annexin V: 9.1+/-3.9 vs. 5.3+/-3.8%, p<0.001). To study the release of PMP into
      plasma, a modified cone-and-plate viscometer was used. Increased release of PMP
      from platelets was observed in diabetic plasma compared to normal plasma under
      high shear stress conditions (2,672+/-645 vs. 1,498+/-386/10(4) plt, p<0.05).
      Therefore, one cause of PMP elevation in NIDDM may be high shear stress. The
      levels of PMP, activated platelets, and soluble adhesion molecules all decreased
      significantly after treatment with cilostazol. These results suggest that
      cilostazol may be useful for the inhibition of both PMP-dependent and 
      independent vascular damage in NIDDM.

PMID- 9759617
TI  - Thromboembolic complications associated with the use of prothrombin complex and
      factor IX concentrates.
AB  - In 1994, shortly after a heat-treated prothrombin complex concentrate (PCC) had
      been withdrawn from the German market due to transmission of hepatitis B, the
      license of another brand was withdrawn, due to 3 acute fatalities associated with
      the use of this product. We report on the clinical data of altogether 5 patients,
      who died during a 3 month period in Germany after having received this brand of
      PCC. All patients had surgery, acquired deficiencies of coagulation factors, and
      underlying diseases predisposing for thrombosis or disseminated intravascular
      coagulation. PCC was administered for the prevention of bleeding. In three
      patients, a drug interaction of PCC with aprotinin may also have played a role.
      Several points, however, are suspicious of a major causative effect of the
      respective product, (a) the close temporal correlation between administration of
      the drug and the subsequent clinical as well as laboratory deterioration, (b) the
      accumulation of these adverse events in a short period of time, when the use and
      market share of this brand increased due to the shortage of other products, and
      (c) laboratory abnormalities of this brand which have been consistently observed
      in several in vitro studies.

PMID- 9759618
TI  - Molecular bases of pseudo-homozygous APC resistance: the compound heterozygosity
      for FV R506Q and a FV null mutation results in the exclusive presence of FV
      Leiden molecules in plasma.
AB  - Pseudo-homozygous APC resistance, the condition resulting from compound
      heterozygosity for FV R506Q (FV Leiden) and quantitative FV deficiency, provides
      a natural model to study the interaction between procoagulant and anticoagulant
      defects. This paper reports a complete FV characterization of a pseudo-homozygous
      APC resistant thrombotic patient. The expression of the patient's non-Leiden gene
      was found to be severely impaired both at the mRNA and protein levels. In
      particular, only FV Leiden molecules were detected in the patient's plasma by
      immunoblotting, which accounts for the observed marked APC resistance. Analysis
      of the FV cDNA obtained by reverse transcription of platelet RNA revealed that
      the mRNA of the non-Leiden gene was extremely reduced in amount. A PAC clone
      containing the whole FV gene was used to design primers for a complete FV exon
      scanning. A 2-bp insertion at nucleotide 3706 in the large exon 13 of the non
      Leiden gene, predicting a frame-shift and premature termination of protein
      synthesis, was identified as responsible for the FV defect. Failure to find any
      case of pseudo-homozygous APC resistance in a large sample (6,804) of blood
      donors suggests that this condition is extremely rare among normal controls and
      that its detection is favoured by the thrombotic risk that it may confer.

PMID- 9759619
TI  - Prothrombin and its derivatives stimulate motility of melanoma cells.
AB  - Several studies indicated that activation of the clotting system may promote the
      growth and the invasive behavior of tumor cells. In the present study, we
      evaluated the migratory response of various melanoma cell lines to several
      clotting factors and prothrombin derivatives (thrombin, fragment 1, fragment 2
      and kringle 1 fragment). Prothrombin, thrombin and fragment 1 stimulated
      chemotaxis of the murine (K-1735 M2, X21) and human A375 (SM) melanoma cell
      lines. Prothrombin and prothrombin fragment 1 showed their maximal chemotactic
      activity at 0.5 approximately 1 microM. Chemotaxis induced by thrombin was
      inhibited by hirudin, but not that induced by prothrombin or fragment 1. Other
      clotting proteins and the fragment 2 and kringle 1 fragment of prothrombin did
      not elicit chemotactic activity. Checkerboard analysis indicated that motility
      was directional with a significant chemokinetic component. The K-1735 M2 cells
      also migrated in a concentration-dependent manner to substratum-bound insoluble
      prothrombin, thrombin or fragment 1. Ligand binding assays showed that both
      prothrombin and fragment 1 bound to K-1735 M2 cells with apparent Kds of 0.5
      microM. This binding was inhibited by an excess concentration of unlabeled
      prothrombin and fragment 1 but not by similar concentrations of other prothrombin
      fragments. These findings suggest that prothrombin and its fragment 1 exert
      chemotactic activity on melanoma cells by different mechanisms and different
      binding sites from that induced by thrombin.

PMID- 9759620
TI  - The effects of standard and low molecular weight heparin on bone nodule formation
      in vitro.
AB  - Previously, we demonstrated in a rat model of heparin-induced osteoporosis that
      low molecular weight heparin (LMWH) produces less bone loss than unfractionated
      heparin, and that only heparin increases osteoclast number and activity. In
      contrast, both heparin and LMWH were found to decrease osteoblast function to a
      similar extent, possibly because at the doses tested both agents produced maximal
      inhibition. To examine the relative effects of heparin and LMWH on osteoblast
      function more closely we used an in vitro bone nodule assay, together with
      measurements of alkaline phosphatase (ALP) activity. Both agents inhibited bone
      nodule formation and ALP activity in a concentration-dependent manner, but 6 to 8
      fold higher concentrations of LMWH were required to achieve equivalent effects.
      The effect of heparin on osteoblast function was both chain-length and negative
      charge-dependent because the ability of defined heparin fragments to inhibit
      nodule formation correlated with their molecular weight (r = 0.98), and N
      desulfated heparin was less inhibitory than heparin. In contrast, the effect of
      heparin on osteoblast function was pentasaccharide-independent because heparin
      with low affinity for antithrombin had similar activity to heparin with high
      antithrombin activity. These findings help to explain mounting clinical evidence
      that the risk of osteoporosis is lower with LMWH than with heparin.

PMID- 9759621
TI  - Interaction of the A1 subunit of factor VIIIa and the serine protease domain of
      factor X identified by zero-length cross-linking.
AB  - We have previously used a solid phase binding assay to localize a Factor X (FX)
      interactive site to the acidic C-terminus of the A1 subunit of FVIIIa (Lapan KA,
      Fay PJ. J Biol Chem 1997; 272: 2082-2088). The complex of FVIII-FX was made
      covalent following reaction with the zero-length cross-linking reagent 1-ethyl-3
      (3dimethylaminopropyl-)carbodiimide hydrochloride (EDC). Western blotting of the
      thrombin-cleaved complex showed that the Al subunit of FVIIIa associated with FX
      heavy chain. The FX-A1 product was also detected following cross-linking to the
      A1/A3-C1-C2 dimer, but not the activated protein C-cleaved A1(336)/A3-C1-C2 form,
      indicating that a residue(s) in the region spanning Met337-Arg372 contributed to
      the intermolecular ion pair(s). A synthetic peptide to this acidic region
      (FVIII337-372) cross-linked to FX and the product was alkaline resistant
      indicating that amide linkage(s) were formed. Sequence analysis of the FX
      FVIII337-372 adduct suggested that the first 12 NH2-terminal residues of the FX
      and peptide do not participate in cross-link formation. Conversion of the cross
      linked product to FXa by RVV-X showed that the peptide was associated with the
      serine protease-forming domain of the heavy chain. These results indicate that
      the association of FVIIIa and FX occurs from a salt linkage(s) formed between
      residues of the A1 acidic C-terminus of the cofactor (within residues 349-372)
      and the serine protease-forming domain of the substrate.

PMID- 9759622
TI  - Proteolysis of tissue factor pathway inhibitor (TFPI) by plasmin: effect on TFPI
      activity.
AB  - An important regulator of the initiation of blood coagulation is the plasma
      glycoprotein, tissue factor pathway inhibitor (TFPI). TFPI inhibits factor Xa and
      factor VIIa/tissue factor complex, thereby dampens the proteolytic cascade of the
      tissue factor pathway. Plasma clot lysis is primarily mediated by the
      fibrinolytic enzyme, plasmin, which is generated through limited proteolysis of
      plasminogen by endogenous or exogenously administered plasminogen activators. In
      this study, the interaction of plasmin with recombinant E. coli-derived TFPI
      (rTFPI) was examined. Plasmin was found to cause a time and concentration
      dependent proteolysis of rTFPI, resulting in the decrease of anti-factor Xa
      (measured by chromogenic substrate assay) and anticoagulant (measured by tissue
      factor-induced clotting assay) activities. Amino-terminal sequencing of the
      proteolytic fragments revealed that plasmin cleaved rTFPI at K86-T87, R107-G108,
      R199-A200, K249-G250, and K256-R257. Western blot analysis showed that
      proteolysis of exogenously added rTFPI also occurred in plasma supplemented with
      urokinase, and this is accompanied by decrease of anticoagulant activity. These
      changes were abolished by addition of aprotinin, an inhibitor of plasmin. These
      data indicate that TFPI is susceptible to proteolysis when plasma fibrinolytic
      system is activated. The results taken together suggest that plasmin degradation
      of TFPI may contribute to rethrombosis after thrombolysis, and may contribute to
      the variability of the efficacy of TFPI in various thrombolysis/reocclusion
      studies reported previously.

PMID- 9759623
TI  - Ristocetin- and thrombin-induced platelet aggregation at physiological shear
      rates: differential roles for GPIb and GPIIb-IIIa receptor.
AB  - We recently reported that washed platelets (WP) activated with ADP and expressing
      surface-bound vWF aggregated in flow through small tubes or in a cylindrical
      couette device at physiological shear rates of G = 300 s(-1)-1000 s(-1) in the
      absence of exogenous ligands, with GPIb-vWF partially, and activated GPIIb-IIIa
      totally required for the aggregation. We have now extended these studies to
      aggregation of platelets "activated" with ristocetin or thrombin. Washed platelet
      suspensions with added soluble vWF and ristocetin (0.3-0.75 mg/ml), or activated
      with thrombin (0.01-0.5 U/ml) but no added ligand, were sheared in a coaxial
      cylinder device at uniform shear rate, G = 1000 s(-1). The collision capture
      efficiency (alphaG) with which small aggregates form (= experimental/calculated
      initial rates of aggregation) was correlated with vWF platelet binding assessed
      by flow cytometry. The vWF-GPIb interaction was exclusively able to support
      ristocetin-mediated shear aggregation of metabolically active platelets, with
      very few vWF monomer equivalents bound per platelet (representing < or = 10
      molecules of 10 million Da) required to yield high capture efficiencies (alphaG =
      0.38+/-.02; n = 11), suggesting rapid and stable bond formations between vWF and
      GPIb. However, platelet surface-expressed vWF, generated by addition of thrombin
      to washed platelets, was found to mediate platelet aggregation with alphaG =
      0.08+/-.01 (n = 6), surprisingly comparable to that previously reported for WP
      and ADP activation. Blocking the GPIIb-Illa receptor decreased alphaG by 95+/-3%
      (n =3), while a monoclonal antibody to the vWF site on GPIb caused a 49+/-7% (n =
      8) decrease in alphaG. The partial role for GPIb thus appears to reflect a
      facilitative function for increasing contact time between flowing platelets, and
      allowing engagement of the GPIIb-IIa receptor to yield stable attachment.

PMID- 9759624
TI  - A heparin-coated circuit maintains platelet aggregability in response to shear
      stress in an in vitro model of cardiopulmonary bypass.
AB  - Alterations in platelet aggregability may play a role in the pathogenesis of
      qualitative platelet defects associated with cardiopulmonary bypass (CPB). We
      circulated fresh heparinized whole blood through tubing sets coated with heparin
      (C group, n = 10) and through non-coated sets (N group, n = 10) as a simulated
      CPB circuit. Shear stress (108 dyne/cm2)-induced platelet aggregation (hSIPA),
      plasma von Willebrand factor (vWF) activity and platelet glycoprotein (GP) Ib
      expression were measured, before, during, and after this in vitro set up of
      circulation. In the two groups, the extent of hSIPA significantly decreased
      during circulation and was partially restored after circulation. Decreases in the
      extent of hSIPA were significantly less with use of heparin-coated circuits.
      There was an equivalent reduction in plasma vWF activity, in the two groups.
      Expression of platelet surface GP Ib decreased significantly during circulation
      and recovered after circulation. Reduction of surface GP Ib expression during
      circulation was significantly less in the C group than that in the N group.
      Decrease in surface GP Ib expression correlated (r = 0.88 in either group) with
      the magnitude of hSIPA, in the two groups. The progressive removal of surface GP
      Ib was mainly attributed to redistribution of GP Ib from the membrane skeleton
      into the cytoskeleton. Our observations suggest that use of heparin-coated
      circuits partly blocks the reduction of hSIPA, as a result of a lesser degree of
      redistribution of GP Ib.

PMID- 9759625
TI  - Platelet associated fibrinogen and ICAM-2 induce firm adhesion of neutrophils
      under flow conditions.
AB  - Surface-bound platelets support selectin-mediated rolling and beta2-integrin
      mediated firm adhesion of neutrophils (PMN) under flow conditions. We examined
      which ligands on platelets mediate this firm adhesion. Surface-bound platelets
      express ICAM-2 and GPIIbIIIa-bound fibrinogen, which are ligands for LFA-1 and
      MAC-1. In a well defined model for vessel wall injury, blood from an
      afibrinogenemic patient was perfused over ECM-coated coverslips to obtain
      fibrinogen-free platelet surfaces. At high shear rates, PMN-adhesion to
      fibrinogen-free platelet surfaces decreased compared to fibrinogen-containing
      controls. Under these conditions, firm adhesion and not rolling was blocked
      demonstrating the importance of fibrinogen in this process. In addition, MAC-1
      and LFA- on PMN and ICAM-2 on platelets played a role in firm adhesion; the
      effect of blocking antibodies was most evident at high shear. The effects of
      fibrinogen depletion and ICAM-2 blocking were additive. In conclusion, multiple
      redundant ligands, like ICAM-2 and fibrinogen, induce firm and shear resistant
      PMN adhesion to platelets under flow conditions. Individually these ligands
      become critical at higher shear. Blocking of two or more interactions also
      interferes with low shear adhesion.

PMID- 9759626
TI  - Analysis of platelet glycoprotein Ia (alpha2 integrin) allele frequencies in
      three North American populations reveals genetic association between nucleotide
      807C/T and amino acid 505 Glu/Lys (HPA-5) dimorphisms.
AB  - Glycoprotein Ia (alpha2 integrin) is a subunit of the heterodimeric membrane
      complex (GPIa/IIa) that mediates platelet adhesion to collagen. Several
      nucleotide sequence variations of GPIa have been described. A nucleotide 1648 G/A
      dimorphism that leads to a Glu/Lys substitution at amino acid 505 is responsible
      for the human platelet antigen system, HPA-5. Recently, two other linked GPIa
      nucleotide dimorphisms involving codons Phe224 and Thr246 were identified: a C/T
      substitution at nucleotide 807 and a G/A substitution at nucleotide 873(1). Using
      restriction enzyme digestion of amplified GPIa genomic DNA fragments (PCR-RFLP)
      to distinguish genotypes, we have determined the allele frequencies of the GPIa
      807C/T and Glu/Lys505 dimorphisms in three North American populations, and a
      panel of non-human primates. Our results indicate a genetic relationship between
      the 807C/T and Glu/Lys505 dimorphisms that leads to an evolutionary model of GPIa
      isoforms.

PMID- 9759627
TI  - Differences in platelet alpha-granule release between normals and immune
      thrombocytopenic patients and between young and old platelets.
AB  - The risk of serious bleeding in patients with immune thrombocytopenic purpura
      (ITP) appears to be less than in comparably thrombocytopenic patients with
      megakaryocytic hypoplasia. It has been proposed that this difference is due to
      enhanced hemostatic activity of young platelets, which are increased in the
      circulation during ITP. We examined alpha-granule release in reticulated
      platelets (RP), which are thought to be the youngest circulating platelets, and
      in older non-reticulated platelets (non-RP) in normal human controls and ITP
      patients. Normal controls had a mean RP of 7%, compared with 42% in ITP patients.
      The mean concentration of thrombin receptor agonist peptide (TRAP) causing 50% of
      control RP to express CD62P (EC50) was 0.82+/-0.08 microM (SEM), significantly
      higher than the TRAP CD62P EC50 for RP in ITP, 0.57+/-0.06 microM (p = 0.04).
      Similarly, the TRAP EC50 for non-RP in controls, 0.84+/-0.09 microM, was
      significantly higher than in ITP, 0.56+/-0.07 microM (p = 0.03), suggesting that
      all platelets in ITP have an enhanced alpha-granule threshold response to TRAP
      compared with controls, while RP and older platelets within each patient group
      have similar threshold sensitivities to TRAP. By contrast, high-dose TRAP caused
      RP to express twice as much mean and total CD62P as non-RP in both ITP patients
      and controls (p <0.05 for both comparisons). We conclude that compared with
      controls, all platelets in ITP are primed to undergo alpha-granule release to
      TRAP, while in both ITP and controls, the newly circulating, reticulated
      platelets have the potential to contribute greater amounts of CD62P surface
      ligand compared with older platelets (non-RP) after stimulation. Both the
      increased RP% and enhanced platelet response to agonist in ITP may contribute to
      maintenance of hemostasis despite thrombocytopenia.

PMID- 9759628
TI  - Abnormal tyrosine phosphorylation linked to a defective interaction between ADP
      and its receptor on platelets.
AB  - ADP, a primary stimulus of platelets, binds to one or more populations of
      receptors on the platelet surface. These receptors are linked to discrete
      activation pathways. Both G proteins and tyrosine kinases have been implicated in
      the cellular responses to this agonist. We have studied a patient with a
      congenital abnormality of ADP-induced platelet aggregation in an effort to gain
      information on the signalling pathways used by ADP. Immunoblotting with a broadly
      reactive rabbit antibody recognizing the GTP-binding domain of G protein alpha
      subunits, and with rabbit antibodies specific for Gialpha1-3, and Galpha12 all
      showed normal reactivity when tested against the patient's platelets. The
      phosphorylation of proteins was studied using an anti-phosphotyrosine MoAb (4G10)
      and platelets stimulated in a platelet aggregometer with ADP, a thromboxane A2
      mimetic (IBOP), TRAP-14-mer peptide and alpha-thrombin. With normal platelets, a
      time-dependent phosphorylation of several bands in the 60 to 130 kDa mol. wt.
      range was observed with all agonists. For the patient, minimal aggregation and
      little or no phosphorylation of proteins of 80-85 kDa (cortactin), 100-105 kDa
      and 125-130 kDa were seen in response to ADP. The aggregation and phosphorylation
      responses were slightly modified in the presence of low doses of thrombin but
      were normal with high doses. Aggregation and tyrosine phosphorylation were
      virtually absent with IBOP, a finding reproduced when normal platelets were
      incubated with IBOP and the CP/CPK ADP scavenging system, thereby underlining the
      role of ADP in the response to IBOP. Our results show that the ADP receptor
      pathway deficient in the patient is linked to a selective tyrosine
      phosphorylation response.

PMID- 9759629
TI  - SR 121787, a new orally active fibrinogen receptor antagonist.
AB  - The aim of this study was to describe the pharmacological properties of SR
      121787, a new antiaggregating drug which is metabolized in vivo into SR 121566, a
      potent non-peptide antagonist of Gp IIb/IIIa. In vitro, SR 121566 antagonized the
      binding of [125I]-fibrinogen (IC50 = 19.8+/-6.3 nM) and of [125I]-L-692,884, an
      RGD-containing peptide (IC50 = 291+/-96 nM) to activated human platelets. SR
      121566 inhibited the aggregation of human platelets induced by ADP, collagen,
      thrombin, arachidonic acid and PAF at concentrations lower than 0.1 microM.
      Adhesion of human platelets to adhesive proteins was inhibited by SR 121566 (IC50
      = 40.3+/-2.5 nM) only when Gp IIb/IIIa and fibrinogen were involved. No effect
      was found with regard to other adhesive proteins and/or other integrins. SR
      121787 demonstrated a potent and sustained antiaggregating effect when
      administered intravenously to baboons at a dose 50 microg/kg, and eight hours
      after the administration of 100 microg/kg, ADP-induced aggregation was still
      strongly inhibited (more than 80%). A single oral administration of 2 mg/kg of SR
      121787 produced a nearly complete inhibition of platelet aggregation for up to 8
      h (ED50 at 8 h = 193+/-20 microg/kg), a significant residual antiaggregating
      activity being still observed 24h after the administration. When administered
      orally to rabbits, SR 121787 exhibited a potent antiaggregating (ED50 = 2.3+/-0.3
      mg/kg) and antithrombotic activity in an arterio-venous shunt thrombosis model
      (ED50 = 10.4+/-0.8 mg/kg). After oral and IV administration, SR 121787 was well
      tolerated suggesting that SR 121787, the most potent and long lasting orally
      active Gp IIb/IIIa antagonist described to date, is a promising antithrombotic
      compound.

PMID- 9759630
TI  - Induction of endothelial cell adhesion molecules by serum and immunoglobulins G
      from a patient with vasculitis and monoclonal gammapathy: potential relevance to
      vasculitis.
AB  - Interactions between endothelial cell adhesion molecules and their beta2 integrin
      adhesive receptors on leukocytes are thought to play a role in the pathogenesis
      of inflammatory diseases and probably vasculitis. We describe a case in whom
      leukocytoclastic vasculitis was associated to a monoclonal immunoglobulin G2
      kappa (IgG2K). During the vasculitic crisis, the patient's serum and the isolated
      IgG from this serum induced the expression of E-selectin, VCAM-1 and ICAM-1 at
      the HUVEC surface, but not tissue factor activity, whereas normal, control serum
      and patient serum at remission were without any effect. A close relationship
      between the vasculitis and the serum level of the monoclonal IgG was observed. We
      suggest that the monoclonal IgG might induce the vasculitis by increasing the
      expression of E-selectin, VCAM-1 and ICAM-1 which facilitate the interaction of
      leukocytes with vascular endothelium.

PMID- 9759631
TI  - Heparin regulates ICAM-1 expression in human endothelial cells: an example of non
      cytokine-mediated endothelial activation.
AB  - Activated endothelial cells up-regulate the expression of several molecules on
      their plasma membranes, including intercellular adhesion molecule-1 (ICAM-1). The
      role of heparin in regulating endothelial cell gene expression is unclear. We
      thus have investigated the ability of heparin to regulate ICAM- gene expression
      by using flow cytometry and the ribonuclease protection assay with human
      umbilical vein and aortic endothelial cells cultured in growth medium
      supplemented with 90 [microg/ml heparin (heparin-sufficient, HS) or in growth
      medium without added heparin (heparin-deficient, HD). We found that HD medium
      increased plasma membrane protein and mRNA for ICAM-1 but not for HLA-DR, even
      though both ICAM-1 and HLA-DR protein and mRNA were inducible by gamma interferon
      (IFN-gamma). In addition, phorbol ester and IFN-gamma increased the expression of
      plasma membrane ICAM-1 or ICAM-1 and HLA-DR, respectively, more in HD medium than
      in HS medium. We found that the HD-mediated increase of ICAM- mRNA was reversible
      by the addition of heparin, and that the half-life of ICAM-1 mRNA was the same in
      both HS- and HD-treated cells. Also, heparin was found to suppress increases in
      ICAM-1 mRNA at a concentration as low as 5 microg/ml. These findings indicate
      that heparin deficiency induces endothelial activation characterized by increased
      ICAM-1, and that such induction is not dependent on cytokines or endotoxin. The
      modulation of ICAM-1 expression by heparin appears to occur at the
      transcriptional level. Thus, heparin may have a role in regulating endothelial
      function by affecting the expression of ICAM-1, thereby impacting upon the trans
      endothelial trafficking of leukocytes.

PMID- 9759632
TI  - Two repressor elements inhibit expression of the von Willebrand factor gene
      promoter in vitro.
AB  - A fragment of the human von Willebrand factor (VWF) gene promoter corresponding
      to sequences -487 to +247 bp functions as an endothelial specific promoter in
      cell culture. We have previously reported that a GATA transcription factor
      functions as an activator and an NF1 like protein functions as a repressor of
      this promoter fragment. We have now identified a second negative regulatory
      element in the VWF promoter that interacts with nuclear factor(s) (designated R)
      in both bovine aortic endothelial and smooth muscle cells. Inhibition of either
      the NF1 or the R repressor alone is not sufficient to activate the VWF promoter
      in smooth muscle cells. The present studies reveal that simultaneous inhibition
      of both repressors activates the VWF promoter in smooth muscle cells. The data
      support a model of selective derepression to explain the endothelial cell
      specific activity of the 487 to +247 fragment of the VWF promoter in vitro.

PMID- 9759633
TI  - Quantitative analysis of von Willebrand factor and its propeptide in plasma in
      acquired von Willebrand syndrome.
AB  - Measurement of the von Willebrand factor (vWF) propeptide, also known as von
      Willebrand antigen II, has been suggested to be helpful in the discrimination of
      congenital von Willebrand disease type I from type 2 and in assessing the extent
      of activation of the endothelium. We performed a quantitative analysis of mature
      vWF and its propeptide in plasma in 8 patients with acquired von Willebrand
      syndrome (AvWS) and in 20 normal individuals. Mature vWF levels were
      significantly lower in AvWS as compared with normal individuals (13.4+/-3.5 vs
      35.6+/-3.3 nM, p <0.001). In contrast, propeptide levels were significantly
      higher in AvWS (11.4+/-1.1 vs 4.7+/-0.2 nM, p <0.001), probably reflecting a
      compensatory increase in vWF synthesis or increased perturbation of the
      endothelium in AvWS. After treatment with DDAVP, propeptide and mature vWF levels
      rose 5-fold in AvWS, whereas propeptide levels were not altered by the infusion
      of a vWF concentrate or treatment with high dose intravenous immunoglobulins,
      indicating that plasma propeptide levels are a reliable reflection of vWF
      synthesis. Measurement of propeptide levels may provide additional information in
      AvWS as to whether decreased levels of mature vWF in the circulation are due to a
      decrease in synthesis or due to an accelerated removal of vWF from the
      circulation.

PMID- 9759634
TI  - Purification and characterization of kaouthiagin, a von Willebrand factor-binding
      and -cleaving metalloproteinase from Naha kaouthia cobra venom.
AB  - A von Willebrand factor (vWF)-binding and -cleaving metalloproteinase, termed
      "kaouthiagin", was purified from the venom of cobra snake Naja kaouthia.
      Kaouthiagin is a monomer with a molecular mass of about 46 kDa and 51 kDa under
      non-reducing and reducing conditions, respectively, and the N-terminal amino acid
      sequence is homologous to high molecular mass snake venom metalloproteinases.
      Kaouthiagin bound to vWF in a divalent ion-independent manner, but the reduced
      kaouthiagin failed to interact with vWF, suggesting that the protein conformation
      maintained by intrachain-disulfide linkages of the molecule is essential for the
      binding to vWF. Neither botrocetin nor bitiscetin, vWF-binding modulators from
      another snake venom, interfered with the binding between kaouthiagin and vWF, but
      a monoclonal antibody VW92-3 specific to the N-terminal region of vWF (residues 1
      910) inhibited the binding. Without affecting platelet GPIb/IX and GPIIb/IIIa,
      kaouthiagin specifically cleaved vWF between residues Pro-708 and Asp-709 in a
      divalent ion-dependent manner to diminish the multimeric structure of vWF in
      plasma, resulting in the loss of ristocetin-induced platelet aggregability and
      the collagen-binding activity of vWF. These results indicate that kaouthiagin is
      a unique metalloproteinase which specifically binds to and cleaves vWF at a
      specific site and that it will be a useful tool for functional dissection of vWF.

PMID- 9759635
TI  - Fibrin-rich and platelet-rich thrombus formation on neointima: recombinant tissue
      factor pathway inhibitor prevents fibrin formation and neointimal development
      following repeated balloon injury of rabbit aorta.
AB  - Thrombus formation and neointimal growth are the critical events in restenosis
      after balloon angioplasty. However, the responses of diseased vessels to injuries
      caused by balloon angioplasty have not been well examined. We investigated the
      thrombus formation and neointimal development following the balloon injury to the
      previously induced neointima in the rabbit aorta and the effects of recombinant
      tissue factor pathway inhibitor (rTFPI) on these responses. Rabbit thoracic
      aortas were subjected to injury with a Fogarty 4F balloon catheter at 1.75 atm
      (first injury), and 4 weeks later the same vessels were subjected to the second
      injury with a Swan-Ganz 5F balloon catheter at 1.4 atm (mild-injury group) or 1.8
      atm (severe-injury group), and immediately after that a retrograde bolus
      injection of rTFPI (100 microg/kg body weight) or saline was performed into the
      injured segments via the central tube of the Swan-Ganz catheter. Twenty minutes
      after the second injury, the injured surfaces were covered with platelet-rich
      thrombi in the mild-injury group and with fibrin-rich thrombi in the severe
      injury group. Damaged intimal smooth muscle cells, which were
      immunohistochemically positive for tissue factor (TF), were observed beneath the
      fibrin-rich thrombi. The neointima 4 weeks after the second injury was
      significantly thicker in the severe-injury group than in the mild-injury group.
      The bolus infusion of rTFPI markedly inhibited fibrin formation on the injured
      surfaces, and significantly reduced the neointimal development in the severe
      injury group at 4 weeks after the second injury. These results indicate that TF
      dependent coagulation pathway is primarily responsible for fibrin-rich thrombus
      formation and may play an important role in neointimal development following the
      balloon injury to the rabbit aortic neointima. Additionally the bolus
      administration of rTFPI to the injured vessels could prevent mural thrombus
      formation and neointimal growth after balloon angioplasty.

PMID- 9759637
TI  - Hepatic vein thrombosis in a patient with mutant prothrombin 20210A allele.

PMID- 9759636
TI  - The antiaggregating and antithrombotic activity of clopidogrel is potentiated by
      aspirin in several experimental models in the rabbit.
AB  - It is unknown whether the addition of aspirin might increase both the efficacy
      and the potency of clopidogrel, a potent and selective ADP blocker. For that
      purpose, the efficacy of clopidogrel (1-20 mg/kg, p.o.) administered orally to
      rabbits alone or in combination with aspirin (0.1-10 mg/kg, p.o.) was determined
      in several experimental models. A potent synergistic effect of the
      clopidogrel/aspirin association was demonstrated with regard to collagen-induced
      platelet aggregation measured ex vivo. Similarly, aspirin potentiated the
      antithrombotic activity of clopidogrel measured with regard to experimental
      thrombosis induced by a silk thread or on stents placed in an arteriovenous
      shunt, thrombus formation following electrical stimulation of the rabbit carotid
      artery and with regard to 111In-labeled platelet deposition on a stent implanted
      in an arteriovenous shunt or on the subendothelium following air drying injury of
      the rabbit carotid artery. A similar potentiating effect of aspirin was obtained
      with regard to myointimal proliferation (restenosis) in the femoral arteries of
      atherosclerotic rabbits which occurred as a consequence of stent placement. The
      clopidogrel/aspirin combination showed only additive-type effects on bleeding
      time prolongation induced by ear transection in the rabbit, therefore showing
      that combined inhibition of cyclooxygenase and ADP's effects provide a marked
      enhanced antithrombotic efficacy. Such a combination may provide substantial
      protection against platelet aggregation leading to thrombotic occlusion at sites
      of endothelial injuries and coronary artery stenosis in humans.

PMID- 9759638
TI  - Prevalence of factor V Leiden and methylenetetrahydrofolate reductase C677T
      mutations in Azerbaijan.

PMID- 9759639
TI  - The mutation C677T in the methylene tetrahydrofolate reductase gene as a risk
      factor for myocardial infarction in the Portuguese population.

PMID- 9759641
TI  - Prevalence of FXIII V34L in populations with different cardiovascular risk.

PMID- 9759640
TI  - Prevalence of FVR506Q and prothrombin 20210A mutations in the Navarrese
      population.

PMID- 9759642
TI  - Chromosomal arrangement of the murine coagulation factor VII and factor X genes.

PMID- 9759643
TI  - Recurrent venous thrombosis despite correction of activated protein C resistance
      following orthotopic liver transplantation.

PMID- 9759644
TI  - Clinical usefulness of D-dimer tests in excluding pulmonary embolism is highly
      dependent upon age.

PMID- 9759645
TI  - Inhibitory effect of argatroban on thrombin-induced MAP kinase activation.

PMID- 9759646
TI  - No direct effects of Shiga toxin 1 and 2 on the aggregation of human platelets in
      vitro.

PMID- 9759647
TI  - Fatal danaparoid-sodium induced thrombocytopenia and arterial thromboses.

PMID- 9759648
TI  - Altered protein localization in melanocytes from Hermansky-Pudlak syndrome:
      support for the role of the HPS gene product in intracellular trafficking.
AB  - Patients with Hermansky-Pudlak syndrome (HPS) exhibit moderate to mild
      hypopigmentation of the skin, hair, and eyes. To understand the inherent basis
      for this reduced pigmentation, pure cultures of melanocytes were derived using
      skin biopsies obtained from four patients with HPS. A nucleotide lesion in the
      HPS gene was identified in these individuals. Expression of HPS mRNA, parameters
      of melanin synthesis, characteristics in ultrastructural morphology, and
      expression of melanocyte-specific proteins were assessed in HPS melanocytes. The
      patients' cells appeared microscopically hypopigmented, and melanin content
      ranged from 0% to 50% of that for normal melanocytes. In cell lysates of HPS
      melanocytes, tyrosine hydroxylase activity was within the normal range, but in
      intact HPS melanocytes, it was almost half that of normal melanocytes. HPS
      melanocytes also appeared refractory to stimulators of melanization, eg, a
      combination of isobutyl methylxanthine and cholera toxin (IBMX/CT). HPS
      melanocytes contained many morphologically normal melanosomes, mostly Stage II
      with a few Stage I or III. After dihydroxyphenylalanine (DOPA) incubation, there
      appeared to be an equal number of Stage II and III melanosomes with the addition
      of a moderate number of Stage IV melanosomes. A characteristic ultrastructural
      feature of most HPS melanocytes was a variety of unusual cellular structures.
      These aberrancies include the following: (a) large membrane-bound complexes
      containing membranous chambers, unpigmented, and pigmented melanosomes, irregular
      deposits of DOPA reaction products, and granular/amorphous material sometimes
      resembling the cytoplasm; and (b) DOPA-positive rings delineated on either side
      by limiting membranes. The expression of tyrosinase-related protein-1 and
      granulophysin, a 40-kd membrane protein originally identified as a component of
      platelet-dense bodies that are undetectable in HPS, was assessed by light
      microscopy immunofluorescence. For both proteins, HPS melanocytes exhibited a
      large granular pattern of expression throughout the cell, which seems to
      correlate with the large membrane complexes observed ultrastructurally. These
      observations support the hypothesis that the HPS gene product is involved in
      organellogenesis. We propose that in the melanocyte, the HPS gene product
      regulates in part the trafficking of melanocyte-specific proteins from the trans
      Golgi network to preformed premelanosomes.

PMID- 9759649
TI  - Cell cycle-related gene abnormalities and product expression in esophageal
      carcinoma.
AB  - In esophageal carcinoma, individual genetic alterations of cyclins, cyclin
      dependent kinase inhibitors, and final effectors of the G1-to-S transition have
      been documented. Our aim was to design a comprehensive analysis of the role and
      clinical significance of some critical genes, namely cyclin D1, MTS1, and Rb. To
      this end, cyclin D1 gene amplification and protein accumulation, Rb gene allelic
      loss and protein expression, and MTS1 gene mutation and DNA methylation were
      investigated in a series of 74 esophageal carcinomas. Cyclin D1 amplification was
      documented in 17 of 55 (31 %) cases, being a feature of squamous cell type (14 of
      17 amplified cases). Cyclin D1 accumulation significantly correlated with lymph
      node metastasis (p < 0.02), advanced tumor stage (p < 0.05), and a reduced
      overall survival rate (p < 0.03). Rb gene loss of heterozygosity occurred in 14
      of 39 (36%) informative cases and was associated with an unfavorable survival
      rate (p < 0.01). MTS1 gene mutations were detected in 2 adenocarcinomas only;
      gene methylation was observed in 17 of 72 cases (24%) without any correlations
      with the variables investigated. A direct association between cyclin D1 and Rb
      gene accumulation (p < 0.0005) and an inverse one between RB loss of
      heterozygosity and MTS1 abnormalities (p < 0.05) emerged from this study. These
      results have important clinical implications because both cyclin D1 and Rb gene
      deregulation are significantly related to an unfavorable survival rate. In
      addition, cyclin D1 amplification is associated with esophageal carcinoma of
      squamous cell type, being totally absent in adenocarcinomas (p < 0.01). The
      combined evaluation of these genes also demonstrates that molecular abnormalities
      of genes belonging to the same pathway are mutually exclusive and unnecessary for
      the neoplastic transformation and tumor progression.

PMID- 9759650
TI  - Salt-sensitive aortic aneurysm and rupture in hypertensive transgenic mice that
      overproduce angiotensin II.
AB  - We studied the effect of excessive salt intake on vascular lesion development in
      hypertensive transgenic mice that overproduce angiotensin II, ie, Tsukuba
      hypertensive mice (THM). At 6 weeks of age, THM and C57BL/6J (controls) were
      given either 1% sodium chloride ("salt-loaded") drinking water or tap water for
      30 days. Salt-loaded THM, but not controls, suffered frequent thoracic or
      abdominal cavity hemorrhage. THM mortality after 7 days of salt loading was 23%;
      after 30 days of salt loading, it rose to 67%. Hemorrhaging occurred due to the
      development of aortic aneurysm and rupture at the aortic arch and aorta near the
      renal arteries. Vascular lesions progressed with structural degeneration of the
      aortic media. Electronmicroscopic analysis revealed that intact THM already
      exhibited vascular remodeling consisting of vascular smooth muscle cells (VSMCs)
      with developed organelles and an increased extracellular matrix. Salt-loaded THM
      suffered aggravated vascular hypertrophy and vascular structure destruction by
      plasma material invasion, necrosis of VSMCs possessing extremely swollen
      cytoplasm and abundant organelles, and interlamellar bleeding, resulting in
      aortic aneurysm and eventual rupture. Interestingly, blood pressure levels and
      heart rates in salt-loaded THM did not differ significantly from those of
      controls; plasma renin activity between drinking regimens was also comparable
      between the two groups. Drinking volume and the concentration of atrial
      natriuretic peptide (ANP) in plasma, however, were significantly higher in salt
      loaded THM than in intact THM. In addition to aneurysm localization, the findings
      regarding drinking volume and plasma ANP suggest that aortic aneurysm and rupture
      in salt-loaded THM occurred as the result of an unknown mechanical stress, other
      than blood pressure, on the aortic wall. High salt ingestion is involved in the
      development of thoracic and abdominal aortic aneurysm in the presence of
      hypertension in the activated renin-angiotensin system. THM should therefore
      serve as a useful animal model for studying the pathogenesis of aortic aneurysm
      accompanied by hypertension.

PMID- 9759652
TI  - Matrix metalloproteinase-mediated extracellular matrix protein degradation in
      human pulmonary emphysema.
AB  - The aim of this study was to investigate the extracellular degrading proteolytic
      cascade proteins referred to as matrix metalloproteinase-1 (MMP-1), MMP-2, MMP-9,
      membrane-type matrix metalloproteinase-1 (MT1-MMP), tissue inhibitors of matrix
      metalloproteinase-1 (TIMP-1), TIMP-2, neutrophil elastase, and alpha1-antitrypsin
      in human pulmonary emphysema. Localization of MMP-1, MMP-2, MMP-8, MMP-9, MT1
      MMP, TIMP-1, and TIMP-2 was verified by immunohistochemical analysis. The results
      of our study indicated that the immunoreactivity of MMP-1, MMP-8, MMP-9, and TIMP
      1 was absent, whereas MT1-MMP and MMP-2 were mainly observed in pneumocytes,
      fibroblasts, and alveolar macrophages. Although MT1-MMP and MMP-2 were observed
      both in emphysematous and normal lung tissue, these immunoreactivities were
      intense in the emphysematous samples. The presence of MMP-1, MMP-2, MMP-9, TIMP
      1, and TIMP-2 was confirmed at mRNA level by reverse transcription-PCR analysis
      and enzyme immunoassay (EIA). However, the only statistical difference that was
      observed was in MMP-2 and MMP-9 (MMP-2: emphysematous samples, 19.1+/-2.1 versus
      control samples, 5.2+/-0.60 microg/g protein, p < 0.05; MMP-9: emphysematous
      samples, 18.4+/-5.6 versus control samples, 8.1+/-2.7 microg/g protein, p <
      0.05). Results of the neutrophil elastase as analyzed by EIA, and alpha1
      antitrypsin levels as detected by laser nephelometric immunoassay, indicated no
      statistical difference between the emphysematous and control groups. In addition
      to the presence of mRNA levels, the level of MT1-MMP according to immunoblot
      analysis increased in the emphysematous samples. Gelatin zymographic analysis
      confirmed the presence of both pro and active forms of MMP-2, and the increased
      ratio of the active form of MMP-2 in emphysematous samples (25.9%+/-2.0% versus
      11.2%+/-3.3%, p < 0.05), indicated in situ activation of MMP-2 by MT1-MMP.
      Elastin zymographic analysis showed elastolytic activity by MMP-2 and MMP-9 but
      not the reported band of macrophage metalloelastase (MMP-12). The data suggest
      that the MT1-MMP/MMP-2/TIMP-2 system plays a significant role in the MMP-mediated
      extracellular matrix degradation and tissue remodeling of emphysematous lungs,
      and thus may contribute to the weakening of lung parenchyma and lead to the
      formation of emphysema.

PMID- 9759651
TI  - Molecular analysis of the human laminin alpha3a chain gene (LAMA3a): a strategy
      for mutation identification and DNA-based prenatal diagnosis in Herlitz
      junctional epidermolysis bullosa.
AB  - Mutations in the genes (LAMA3, LAMB3, and LAMC2) encoding the subunit
      polypeptides of the cutaneous basement membrane zone protein laminin 5 have been
      reported in different forms of junctional epidermolysis bullosa (JEB), an
      inherited blistering skin disease. In this study, we present the complete exon
      intron organization of the "a" transcript of the laminin alpha3 chain gene,
      LAMA3a, which is expressed primarily in the skin. We have performed fine
      resolution mapping of this gene on chromosome 18q11.2 using a human-hamster
      radiation hybrid panel. We have also developed a mutation-detection strategy
      based on the exon-intron structure of LAMA3a. This strategy, based on PCR
      amplification of genomic sequences, followed by heteroduplex scanning and
      automated nucleotide sequencing, was used for successful mutation screening in a
      family with the lethal (Herlitz) type of JEB, and two novel LAMA3 mutations were
      identified in the proband. The mutations consisted of a single-base pair deletion
      in LAMA3a exon A11 on the paternal allele, designated 1239delC, and a two-base
      pair deletion in LAMA3a exon A23 on the maternal allele, designated 2959delGG.
      This information was also used for DNA-based prenatal testing in a subsequent
      pregnancy in this family. Collectively, these results attest to our expanding
      capability to elucidate the genetic basis of various forms of epidermolysis
      bullosa using molecular techniques.

PMID- 9759653
TI  - Permanent skin replacement using engineered epidermis containing fewer than 5%
      syngeneic keratinocytes.
AB  - This study was conducted to investigate permanent skin replacement using
      heterologous (syngeneic-allogeneic) epidermal substitutes containing fewer than
      5% syngeneic keratinocytes. Keratinocytes were isolated from the skin of new-born
      Balb/c (B) and C3H/HeN (C) mice and cocultured in different ratios: 20%B-80%C,
      10%B-90%C, 5%B-95%C, and 2%B-98%C (and vice versa). After 4 to 5 days, graftable
      epidermal substitutes were obtained and transplanted onto adult Balb/c or C3H/HeN
      male mice. Recipients always received the heterografts containing the lower
      percentage of their own keratinocytes. On Days 15 and 30 postgrafting, all
      heterografts showed significant graft take (> 75%) and skin replacement compared
      with allografts. Regenerated tissues were well structured and well vascularized.
      These tissues contained only syngeneic keratinocytes. These results led us to
      question whether this was an active immune situation. Structural analyses
      revealed the presence of leukocyte infiltration that was dependent on the
      percentage of allogeneic keratinocytes present in the heterologous implant.
      However, even with the 2% syngeneic-98% allogeneic implant, infiltration was
      lower than with the allograft. Leukocyte phenotyping confirmed the presence of
      immune cells infiltrating the heterologous implants and revealed the involvement
      of CD8+ and CD4+ lymphocytes in this immune activation. The percentages of these
      two cell populations were lower than those obtained with the allografts,
      suggesting moderate cellular activation after each heterograft compared with the
      allografts. In conclusion, it is possible to generate functional skin even after
      2% syngeneic-98% allogeneic heterografts; there was moderate cellular immune
      activation compared with the allografts.

PMID- 9759654
TI  - Acquired resistance of a mammalian cell line to hypoxia-reoxygenation through
      cotransfection of Kir6.2 and SUR1 clones.
AB  - Reoxygenation after transient hypoxia is a common clinical condition that often
      causes greater tissue damage than persistent hypoxia itself. This warrants the
      development of a means to protect cells against hypoxia-reoxygenation injury.
      Adenosine triphosphate (ATP)-sensitive K+ (KATP) channels have been proposed to
      play an essential role in the mechanisms of endogenous cellular protection. Thus
      far, however, KATP channel proteins have not been exploited to generate an injury
      resistant cellular phenotype by delivering KATP channel genes into injury-prone
      cells. A first step in this direction is the evaluation of the outcome of
      transferring genes encoding KATP channels into a KATP channel-deficient cell type
      exposed to metabolic stress. Untransfected COS-7 monkey kidney cells, which
      natively lack KATP channels, were found to be vulnerable to hypoxia-reoxygenation
      injury, which induced cytosolic Ca2+ loading, as measured by digital
      epifluorescent imaging. COS-7 cells cotransfected with KATP channel genes, Kir6.2
      and SUR1, gained resistance to hypoxia-reoxygenation. This acquired resistance
      was abolished by glyburide, the KATP channel antagonist. We have previously shown
      that Kir6.2 and SUR1 physically associate to form a functional KATP channel, not
      reconstituted by either of the subunits alone. Transfection with individual
      channel subunits, Kir6.2 or SUR1, failed to produce resistance to hypoxia
      reoxygenation induced Ca2+ loading. This is a first demonstration that transfer
      of KATP channel subunits can generate an injury-resistant cellular phenotype. The
      findings from this study may, thus, provide a framework for future therapeutic
      strategies based on gene delivery of KATP channel subunits in cells and tissues
      vulnerable to hypoxia-reoxygenation insults.

PMID- 9759655
TI  - Urokinase-dependent angiogenesis in vitro and diacylglycerol production are
      blocked by antisense oligonucleotides against the urokinase receptor.
AB  - The plasminogen activator system is known to play a crucial role in the
      angiogenesis process by modulating the adhesive properties of endothelial cells
      to the extracellular matrix and cell-cell interaction. In the present study, we
      demonstrated that the urokinase-type plasminogen activator (u-PA) induced
      neovascular growth in the avascular rabbit cornea and dose-dependently promoted
      growth, chemotaxis, and matrix invasion of cultured endothelial cells.
      Interaction between u-PA and its receptor appears to be mandatory for the
      angiogenic effect of u-PA because monoclonal antibodies anti-u-PA and anti-u-PA
      receptor (u-PAR) blocked the proangiogenic effects of u-PA at the endothelial
      cell level. We then assessed the signaling pathway activated in endothelial cells
      by u-PA. u-PAR activation by u-PA produced de novo synthesis of diacylglycerol
      (DAG) from glucose by a cytochalasin B-inhibitable mechanism, indicating the
      involvement of a specific glucose transporter (GLUT). Endothelial cells expressed
      GLUT2, whose activation was tyrosine kinase-dependent and protein kinase C (PKC)
      independent. The increase of glucose uptake led to DAG production, which resulted
      in PKC activation/translocation. Impairment of u-PAR availability by monoclonal
      antibodies and by antisense oligonucleotides (aODN) against u-PAR mRNA inhibited
      glucose uptake, DAG neosynthesis, and PKC activation, resulting in the blockade
      of endothelial cell proliferation, chemotaxis, and chemoinvasion. These data
      suggest that u-PAR activation consequent to the binding of u-PA can be regarded
      as an "angiogenic switch" and disclose the possibility that an anti-u-PAR aODN
      strategy may efficiently target endothelial cell function to control angiogenesis
      in vivo.

PMID- 9759656
TI  - Identification of a lipocalin in mucosal glands of the human tracheobronchial
      tree and its enhanced secretion in cystic fibrosis.
AB  - Members of the lipocalin protein family are characterized by their ability to
      bind small hydrophobic molecules. Some of them are known to be produced by
      various glands and secretory cells. Under certain conditions, these proteins
      would be ideally suited for clearance of lipophilic, potentially harmful
      substances and might also act as protection factors in airway secretions. We
      therefore used RT-PCR analysis with a set of oligonucleotide primers deduced from
      conserved regions of lipocalin members to identify specific RNA isolated from
      human trachea. With two of these oligonucleotide primers, a positive result was
      obtained. Sequencing of the RT-PCR products revealed that the DNA fragments were
      identical to the lipocalin 1 (LCN1) encoding cDNA. LCN1 is an unusual lipocalin
      member that binds a variety of lipophilic compounds and exhibits cysteine
      proteinase inhibitor and antimicrobial activities. The local production and
      topographic distribution of LCN1 in the human tracheobronchial tree was then
      investigated by immunoperoxidase staining on thin-layer sections using a specific
      antiserum. LCN1 was detectable in the acini of serous mucosal glands and
      sometimes within the glandular lumen, suggesting excretion of the protein. The
      latter finding was tested and verified by Western blot analysis of bronchial
      secretions of healthy individuals. Furthermore, the results of SDS-PAGE and
      Western blot analysis of bronchial secretions from patients with cystic fibrosis
      (CF), which are usually characterized by an increase of airway lipids, suggested
      that LCN1 secretion was enhanced. Northern blot analysis of RNA from normal
      trachea and RNA isolated from tracheal biopsies of patients with CF indicated
      that induced secretion was due to an up-regulated expression of the LCN1 gene.
      Thus, our investigations present the first clear evidence that LCN1 is induced in
      infection or inflammation and support the idea that this lipocalin functions as a
      physiologic protection factor of epithelia in vivo.

PMID- 9759657
TI  - Down-regulation of E-cadherin in mouse skin carcinoma cells enhances a migratory
      and invasive phenotype linked to matrix metalloproteinase-9 gelatinase
      expression.
AB  - To assess the role of gelatinases in mouse skin tumor progression and their link
      to the expression of E-cadherin (E-CD), the cell-cell adhesion protein, we used
      the highly metastatic squamous HaCa4 cell line and several HaCa4-derived clones
      obtained by transfection of the mouse E-CD cDNA. Expression of matrix
      metalloproteinase-9 (MMP-9) mRNA and protein activity were present in E-CD (-)
      HaCa4 and control clones in culture, but they were strongly diminished in E-CD
      (+) clones (E24 and E62) at subconfluence. To explore the suppressive effect of
      the cell-cell contacts mediated by E-CD on MMP-9 expression, we introduced a
      plasmid encoding mouse E-CD antisense cDNA into the E24 cell clone. The
      transfectant P1-clones obtained with reduced or absent E-CD expression showed
      increased levels of MMP-9 gelatinase, motility in vitro, and metastatic potential
      in vivo. Expression of MMP-9 in the various cell clones was also negatively
      modulated by cell density, but this effect was much stronger in E-CD (+) cells,
      despite the fact that all of the cell clones analyzed maintained the expression
      of P-cadherin and made cell-cell contacts at high cell density. Our results
      indicate that in this cell system, the E-CD-mediated cell-cell contacts are
      involved in the down-regulation of MMP-9 expression. Thus, the loss of E-CD
      triggers a migratory and invasive phenotype in mouse squamous carcinoma cells.

PMID- 9759658
TI  - Amplification of c-myc, K-sam, and c-met in gastric cancers: detection by
      fluorescence in situ hybridization.
AB  - Gene amplifications of c-myc, K-sam, and c-met were examined in cancer nuclei
      isolated from 154 primary gastric adenocarcinomas by fluorescence in situ
      hybridization (FISH) using cosmid probes for 8q24 (c-myc locus) and 7q31 (c-met),
      as well as a DNA probe for K-sam synthesized by PCR. The results were compared
      with those of Southern blot analysis. Dual-color FISH using gene locus and
      chromosome-specific probes detected gene amplifications of c-myc in 24 tumors
      (15.5%), c-met in 6 tumors (3.9%), and K-sam in 3 tumors (2.9%). The six tumors
      with c-myc amplification had also been found to have amplified c-erbB-2 in our
      previous study, and coamplification of c-myc and c-met was found in two other
      tumors. This technique also differentiated the amplified genes on the homogeneous
      staining region (HSR) and on double minute chromosomes (DMs) in metaphase spreads
      and interphase nuclei of cell lines established from poorly differentiated
      adenocarcinomas, KATO III, SNU 16, and HSC 39. Examination of FISH images of
      these cell lines suggested that the high-level amplifications of c-myc found in
      primary tumors occurred mainly on DM in four tumors and on HSR in one, and those
      of K-sam occured on DM in two tumors and on HSR in one. No high-level
      amplification of c-met was found. These high-level amplifications were also
      detected in formalin-fixed, paraffin-embedded tissues from primary gastric tumors
      and metastatic lymph nodes, in some of which heterogeneity of gene amplification
      was demonstrated within the same tumor. We conclude that FISH is an important
      tool for examining the proto-oncogene aberrations in intact cells in solid
      tumors.

PMID- 9759659
TI  - Alterations in classical cadherins associated with progression in ulcerative and
      Crohn's colitis.
AB  - Human colitis is a condition associated with a spectrum of altered morphologic
      changes and cellular adhesion. The role of cadherins, which are powerful
      morphoregulatory cell adhesion molecules, in colitis is provocative and as yet
      unknown. Herein, we present results that suggest a strong correlation between the
      deregulation of two cadherin molecules, E- and P-cadherins, and the progression
      of human colitis. We examined the expression and structural integrity of E- and P
      cadherins in inflamed, dysplastic, or neoplastic human ulcerative colitis (UC)
      (n=58), human Crohn's colitis (n = 30), and normal tissue (n = 20) to assess
      cadherin function in normal and abnormal epithelium. E-cadherin is strongly
      expressed in normal colorectal epithelium, whereas in left-sided UC it is either
      down-regulated or has a single-base pair mutation in exon 4 resulting in an amino
      acid alteration (6 of 58 UC cases). By contrast, P-cadherin is dramatically up
      regulated in both Crohn's disease and ulcerative colitis and especially in
      dysplastic ulcerative tissue. In vitro transfected SW-480 colorectal cells
      containing E-cadherin mutations identical to those in vivo were associated with
      increased spontaneous disaggregation compared with cells transfected with wild
      type E-cadherin. Based on this evidence, we hypothesize that a small subset of
      colorectal cells expressing mutant E-cadherin are associated with widespread
      ulceration, whereas those expressing P-cadherin are associated with a rapidly
      dividing immature phenotype that includes dysplasia. The differential expression
      of mutated and wild-type cadherins examined herein are associated with a broad
      spectrum of abnormal epithelial phenotypes, lymphocyte integrin binding, and
      resistance to denudation, as is seen in the colitis adenocarcinoma sequence.

PMID- 9759660
TI  - Abnormal distribution of the non-Abeta component of Alzheimer's disease amyloid
      precursor/alpha-synuclein in Lewy body disease as revealed by proteinase K and
      formic acid pretreatment.
AB  - The precursor of the non-Abeta component of Alzheimer's disease amyloid (NACP)
      (also known as alpha-synuclein) is a presynaptic terminal molecule that
      abnormally accumulates in the plaques of Alzheimer's disease (AD) and in the Lewy
      bodies (LBs) of Lewy body variant of AD, diffuse Lewy body disease, and
      Parkinson's disease. To better understand the distribution of NACP/alpha
      synuclein and its fragments in the LB-bearing neurons and neurites, as well as to
      clarify the patterns of NACP/alpha-synuclein compartmentalization, we studied
      NACP/alpha-synuclein immunoreactivity using antibodies against the C-terminal, N
      terminal, and NAC regions after Proteinase K and formic acid treatment in the
      cortex of patients with LBs. Furthermore, studies of the subcellular localization
      of NACP/alpha-synuclein within LB-bearing neurons were performed by immunogold
      electron microscopy. These studies showed that the N-terminal antibody
      immunolabeled the LBs and dystrophic neurites with great intensity and, to a
      lesser extent, the synapses. In contrast, the C-terminal antibody strongly
      labeled the synapses and, to a lesser extent, the LBs and dystrophic neurites.
      Whereas Proteinase K treatment enhanced NACP/alpha-synuclein immunoreactivity
      with the C-terminal antibody, it diminished the N-terminal NACP/alpha-synuclein
      immunoreactivity. Furthermore, formic acid enhanced LB and dystrophic neurite
      labeling with both the C- and N-terminal antibodies. In addition, whereas without
      pretreatment only slight anti-NAC immunoreactivity was found in the LBs, formic
      acid pretreatment revealed an extensive anti-NAC immunostaining of LBs, plaques,
      and glial cells. Ultrastructural analysis revealed that NACP/alpha-synuclein
      immunoreactivity was diffusely distributed within the amorphous electrodense
      material in the LBs and as small clusters in the filaments of LBs and neurites.
      These results support the view that aggregated NACP/alpha-synuclein might play an
      important role in the pathogenesis of disorders associated with LBs.

PMID- 9759662
TI  - Advancing dental research in the 21st century.

PMID- 9759663
TI  - The road to pulp biology research: a personal odyssey.

PMID- 9759661
TI  - Dendritic mast cells in the human nasal mucosa.
AB  - Human mast cells can be divided into two subtypes: MCTC cells, which contain
      tryptase and chymase, and MCT cells, which contain tryptase only. Herein we have
      used a combination of histamine, tryptase and chymase immunohistochemistry as a
      novel approach to the study of mast cells. Using this technique, we have
      discovered a new type of MCTC mast cell in biopsies of the nasal mucosa from
      healthy subjects and allergic patients. These mast cells have histamine-positive,
      dendrite-like cellular processes. Some cells have only one slender process,
      whereas other cells have several long processes extending from different parts of
      the cell body. Some of the cellular processes divide into two or three terminal
      branches, and histamine is sometimes found in small swellings along the course of
      the processes. Our findings contribute new aspects to the concept of mast cell
      heterogeneity. Thus, human mast cells may vary not only with respect to mediator
      content, but also with respect to gross morphologic features such as the presence
      of dendrite-like cellular processes. The recognition of this extreme
      heterogeneity may be an important step toward a better understanding of mast cell
      biology.

PMID- 9759664
TI  - Commensal communism and the oral cavity.
AB  - The world we live in contains unimaginable numbers of bacteria, and these and
      other single-celled creatures represent the major diversity of life on our
      planet. During the last decade or so, the complexity and intimacy of the
      interactions which occur between bacteria and host eukaryotic cells during the
      process of infection have begun to emerge. The study of such interactions is the
      subject of the new discipline of cellular microbiology. This intimacy of
      bacteria/host interactions creates a major paradox. The average human being is
      90% bacteria in terms of cell numbers. These bacteria constitute the commensal or
      normal microflora and populate the mucosal surfaces of the oral cavity,
      gastrointestinal tract, urogenital tract, and the surface of the skin. In
      bacterial infections, much of the pathology is due to the release of a range of
      bacterial components (e.g., modulins such as lipopolysaccharide, peptidoglycan,
      DNA, molecular chaperones), which induce the synthesis of the local hormone-like
      molecules known as pro-inflammatory cytokines. However, such components must also
      be constantly released by the vast numbers of bacteria constituting the normal
      microflora and, as a consequence, our mucosae should constantly be in a state of
      inflammation. This is patently not the case, and a hypothesis is forwarded to
      account for this "commensal paradox", namely, that our commensal bacteria and
      mucosal surfaces exist in a state of bio-communism, forming a unified "tissue" in
      which interactions between bacteria and epithelia are finely balanced to ensure
      bacterial survival and prevent the induction of damaging inflammation. Evidence
      is emerging that bacteria can produce a variety of proteins which can inhibit the
      synthesis/release of inflammatory cytokines. The authors predict that such
      proteins are simply one part of an extensive signaling system which occurs
      between bacteria and epithelial cells at mucosal surfaces such as those found in
      the oral cavity.

PMID- 9759665
TI  - The riddle of the large loss in bite force after fast jaw-closing movements.
AB  - In unloading experiments (in which the resistance to a forceful static bite is
      suddenly removed), it is shown that the residual bite force (when the jaw system
      is arrested shortly after the unloading) is remarkably small. For example, of a
      100-N initial bite force, only 18 N is left after a jaw travel distance of 5.0
      mm. The present experiments were designed to study whether the magnitude of the
      low residual bite force is dependent on the initial bite force, the initial
      degree of mouth opening, and the distance of jaw travel. Furthermore, we analyzed
      whether the low magnitude of the residual force can be attributed to reflex
      events of the jaw muscles or to the force-length properties of the jaw-closing
      muscles. It was found that the residual forces are largely dependent on the
      distance of jaw travel and are barely sensitive to variations in initial mouth
      opening. The relative residual forces are independent of the magnitude of the
      initial bite force. The maximum residual forces are on the order of 25% of the
      initial bite force after a jaw travel of 4.5 mm. The low values of the residual
      forces cannot be attributed to reflex events, because it took about 80 ms for the
      masseter muscles to decrease their force to a 50% level after their excitation
      was switched off. Furthermore, it was shown that the force-length properties of
      the jaw-closing muscles are not responsible for the small values of the residual
      forces, since over the trajectories used in the present experiments, the
      sarcomere lengths of the jaw-closing muscles were beyond their optimum. It is
      suggested that the low residual forces are brought about by (1) a non-uniform
      sarcomere behavior of the jaw-closing muscles when contracting, or (2) a long
      lasting change in the myofilament system of the closing muscles induced by the
      sudden shortening of muscle fibers.

PMID- 9759668
TI  - Expression of transforming growth factor-beta 1 (TGF-beta1) in the developing
      periodontium of rats.
AB  - Transforming growth factor-beta 1 (TGF-beta1) has been reported to be expressed
      within several tissue compartments of developing molar crowns and therefore is
      implicated in tooth development. Additionally, TGF-beta1 may also play a crucial
      role in tissue repair and regeneration. The aim of this study was to determine
      the distribution of TGF-beta1 in the developing periodontal attachment apparatus
      (cementum, periodontal ligament, and alveolar bone) in Lewis rats. Animals aged
      3, 6, and 12 wks were killed, their mandibles removed, fixed, demineralized, and
      processed in paraffin. The localization of TGF-beta1 in tissues was detected by
      polyclonal goat antibodies against human TGF-beta1 by means of immunoperoxidase
      techniques. TGF-beta1 messenger RNA was detected by in situ hybridization with a
      cocktail oligonucleotide probe. Cell counts were determined for analysis of the
      percentage of cells stained positive for TGF-beta1. Results revealed that TGF
      beta1 was expressed in the developing alveolar bone, periodontal ligament, and
      cementum at all stages of tissue development studied. Staining was stronger at
      sites of cementum and alveolar bone compared with the periodontal ligament.
      Intensity of the positive staining, based on 3 grades, indicated a similarity
      between the tissues obtained from different ages, but varied between several cell
      types. Cementoblasts and osteoblasts stained more strongly than fibroblasts.
      Large numbers (approximately 90%) of the osteocytes in developing bone expressed
      TGF-beta1; however, in mature bone, fewer osteocytes stained for TGF-beta1. The
      percentages of positively stained cementoblasts, osteoblasts, and fibroblasts in
      the periodontal space were greater at the apical portion than at the cervical
      portion of the root. TGF-beta1 mRNA was expressed in osteoblasts, some bone
      marrow cells, cementoblasts, and fibroblasts. This study indicates that TGF-beta1
      may play an important role in the modulation of tissue formation and development
      of the periodontium.

PMID- 9759666
TI  - cDNA cloning of S100 calcium-binding proteins from bovine periodontal ligament
      and their expression in oral tissues.
AB  - The periodontal ligament (PDL) is a unique tissue that is crucial for tooth
      function. However, little is known of the molecular mechanisms controlling PDL
      function. To characterize PDL cells at the molecular level, we constructed a cDNA
      library from bovine PDL tissue. We then focused on the isolation of S100 calcium
      binding proteins (CaBPs), because they mediate Ca2+ signaling and control
      important cellular processes such as differentiation and metabolism. We screened
      the PDL cDNA library with a mouse S100A4 cDNA, and cloned the bovine cDNAs of two
      S100 CaBPs (S100A4 and S100A2). In northern blotting analysis, the highest
      expression of S100A4 was detected in PDL from erupted teeth (PDLE). PDL from
      teeth under eruption (PDLU) showed a lower expression of S100A4, and its
      expression in gingiva was faintly detectable. S100A4 expression was also high in
      the pulp tissue followed by the dental papilla of the tooth germ. S100A2
      expression was high in PDLE and gingiva. Interestingly, only PDLE exhibited a
      high expression of both S100A4 and S100A2. PDLE also expressed the highest level
      of beta-actin, a target cytoskeletal protein for S100A4. It is conceivable that
      the high expression of S100A4 in PDLE is a result of the maturation of the PDL
      and/or a response to mechanical stress generated by mastication. Since there was
      a marked difference of S100A4 expression between PDL and gingiva, we propose that
      S100A4 could be a useful marker for distinguishing cells from these two tissues.

PMID- 9759667
TI  - Serum or growth factor deprivation induces the expression of alkaline phosphatase
      in human gingival fibroblasts.
AB  - We have previously reported that the increased expression of alkaline phosphatase
      (ALP) activity is a phenotypic characteristic of gingival fibroblasts present in
      chronic inflammatory periodontal lesions. We hypothesized that ALP might be
      induced in gingival fibroblasts by environmental factors. In the present study,
      we investigated the factors influencing the induction of ALP expression in
      fibroblasts derived from healthy human gingiva. The withdrawal of serum from
      confluent cultures of fibroblasts increased the number of cells positive for ALP
      activity and protein, without their proliferation. Suramin, a growth factor
      antagonist, induced ALP expression in cells cultured with serum. Serum re
      addition or exposure to platelet-derived growth factor-AB and/or insulin-like
      growth factor I suppressed ALP induction and caused cell growth. ALP-positive
      cells could survive for up to 6 weeks after serum deprivation, a condition
      inducing cell death via apoptosis. These results demonstrate that serum or growth
      factor deprivation induces the expression of ALP in gingival fibroblasts. ALP
      expression is negatively correlated with cell growth and accompanied by a change
      into serum-growth-factor-independent survival.

PMID- 9759669
TI  - Morphometric studies of collagen and fibrin lattices contracted by human gingival
      fibroblasts; comparison with dermal fibroblasts.
AB  - Cell shape variations and substratum re-organization during contraction of
      floating collagen and fibrin lattices seeded with human gingival fibroblasts were
      determined by computerized image analysis of light and scanning electron
      microscopic images. Data were compared with those obtained with lattices
      populated with human dermal fibroblasts. The extent of collagen lattice
      contraction was similar with both cell types, resulting in a two-fold decrease in
      the area fractions occupied by collagen fibers. Fibroblasts exhibited a rounded
      shape (form factors equal to 0.8 and 0.7 for gingival and dermal cells,
      respectively) at day 1 of culture; they possessed a more elongated appearance
      (with form factors equal to 0.3 and 0.15 for gingival and dermal cells,
      respectively) at day 7. Continuous (gingival) and discontinuous (dermal) layers
      of cells were evidenced at the cortex of lattices. Contractions were associated
      with a significant reduction of the diameters of collagen fibers. Re-organization
      of substratum, as analyzed by the "Rose of Directions" technique, was evidenced
      only at the vicinity of filopodia where fibers ran parallel to these protrusions.
      Several lysed matrix cavities were observed when fibrin lattices were populated
      with gingival but not dermal fibroblasts at day 5 of culture. Although cells in
      fibrin lattices exhibited morphometric parameters comparable with those in
      collagen lattices, no fibroblast layers could be demonstrated at gel peripheries.
      Fibrin matrices consisted of an isotropic network of entangled fibrin filaments
      from the start of culture, and only a slight reduction of the diameters of fibrin
      fibers could be evidenced in dermal fibroblast-populated lattices. Fibrinolysis
      at the vicinity of gingival fibroblasts led to an entire re-organization of
      substratum toward the formation of larger fibers. The differential behavior of
      gingival vs. dermal fibroblasts inside fibrin but not collagen matrices could
      therefore partly explain the increased rate of remodeling of gingiva as compared
      with dermis.

PMID- 9759670
TI  - Relationship between growth and the pattern of tooth initiation in alligator
      embryos.
AB  - The temporal and spatial patterns in which teeth are initiated in the growing
      jaws of embryos are constant for a species but different for different species.
      The sources of the patterns have been explained in two ways. First, they are the
      outcome of reactions between molecules created at stationary targets and those
      which diffuse through embryonic tissues (e.g., Edmund, 1960). Second, Osborn
      (1978) supposed that the patterns mirror the way a (mixed) population of parent
      cells, the tooth clone, grows. Westergaard and Ferguson (1986, 1987, 1990)
      concluded, from their observations of the sequence of tooth initiation in
      alligators, that the complicated sequences in which 20 teeth are initiated in
      each tooth quadrant could not be explained by jaw growth. The present study
      attempts to refute this criticism by means of measurements made from the raw data
      published by Westergaard and Ferguson. These data reveal that new teeth, here
      called primary teeth, are added at a constant rate at the back of the jaw.
      Interstitial growth of the cells between primary teeth creates space for
      secondary teeth in secondary regions. The secondary regions increase in length
      exponentially with time. The sequence in which teeth are initiated in the growing
      secondary regions was found to be the same in every part of the upper and lower
      jaws. It was accurately reproduced by a computer program based on a linear
      contraction rate of inhibitory zones and exponential growth of secondary regions.
      The results suggest that the posterior progress zone in alligator embryos grows
      about 125 microm a day. Newly initiated tooth germs are surrounded by an
      inhibitory zone about 250 microm in diameter. These zones contract from 20 to 30
      microm a day until they are about 170 microm in diameter. The sequences in which
      tooth positions are initiated in embryos may be more the result of the pattern in
      which cells escape from molecules that inhibit induction rather than the pattern
      in which cells create molecules that initiate induction.

PMID- 9759671
TI  - The association between water-borne fluoride and bone mineral density in older
      adults.
AB  - While the benefit of fluoridation in the prevention of dental caries has been
      overwhelmingly substantiated, the effect of fluoride on bone mineral density is
      less clear. This cross-sectional study was designed to compare the bone mineral
      densities of older adults exposed to various levels of fluoride from community
      water systems. Participants were recruited from 3 rural communities with
      naturally occurring fluoride in their water systems at 0.03, 0.7, and 2.5 mg/L.
      All adults, age 60 and over, were eligible if they were ambulatory and had a long
      term history (> or = 20 yrs) of ingesting city water. Bone mineral density (BMD)
      was measured by means of dual-energy x-ray absorptiometry at 3 anatomical sites:
      lumbar spine, proximal femur, and forearm. A total of 353 white non-Hispanic
      women and 317 white non-Hispanic men took part in the study. When the data were
      stratified by city of residence and gender, men and women living in the community
      with high levels of fluoride in their community water system had significantly
      higher lumbar spine BMD than their counterparts from the communities with low and
      moderate fluoride levels. The women in the high-fluoride community had
      significantly higher proximal femur BMD, but there were no statistically
      significant differences among men in either proximal femur or forearm BMD. Long
      term exposure (> or = 20 yrs) to higher levels of fluoride appears to have a
      positive impact on lumbar spine and proximal femur BMD. Based on the results of
      this study, exposure to fluoride at levels considered "optimal" for the
      prevention of dental caries (from 0.7 to 1.2 mg/L) appears to have no significant
      impact on bone mineral density. The relationship between higher levels of
      fluoride exposure and bone mineral density requires further investigation.

PMID- 9759672
TI  - Interfacial characteristics of resin-modified glass-ionomer materials: a study on
      fluid permeability using confocal fluorescence microscopy.
AB  - The tooth interface with resin-modified glass-ionomer cements (RM GICs) is poorly
      understood. This study examined the interface, especially with dentin. Cervical
      cavities in extracted teeth were restored with Fuji II LC, Vitremer, Photac-Fil,
      or a conventional GIC, Fuji Cap II. Fluorescent dye was placed in the pulp
      chambers for 3 hrs before the specimens were sectioned. Examination of the
      tooth/material interface with a confocal microscope showed that dye uptake by the
      restoration varied among materials. A "structureless", non-particulate, highly
      stained layer of GIC was observed next to dentin in Fuji II LC. This layer varied
      in width, was prominent where the dentin tubules were cut "end-on" and in areas
      closer to the pulp, and was not seen adjacent to enamel. Vitremer showed minimal
      dye uptake, and the "structureless" layer was barely discernible. Photac-Fil
      showed more uniform uptake and absence of this layer. Cracking of enamel was also
      noted with these materials. The conventional GIC did not show any dye uptake,
      presence of a "structureless" layer, or enamel cracking. We elucidated the
      potential mechanisms involved in the formation of a "structureless" interfacial
      layer in Fuji II LC by studying the variables of cavity design, surface pre
      treatment, water content of the tooth, time for it to develop, early finishing,
      and coating of the restoration. This layer, the "absorption layer", is probably
      related to water flux within the maturing cement, depending on environmental
      moisture changes and communication with the pulp in a wet tooth. The
      "micropermeability model" was useful in this study of the interfacial
      characteristics of RM GICs.

PMID- 9759673
TI  - The relationship of pregnancy, hormones, and melanoma.
AB  - There has been considerable interest in the relationship of pregnancy and
      melanoma. Since 1951, a number of case reports have suggested that pregnancy may
      induce or exacerbate melanoma. Likewise, there has been concern over the
      relationship between exposure to oral contraceptives (OCs) or hormone replacement
      therapy (HRT) and possible increased risk of melanoma. We critically reviewed:
      (1) controlled clinical trials to assess the effect of pregnancy on the prognosis
      of melanoma; and (2) epidemiological data to evaluate the risk of melanoma after
      exposure to OCs or HRT. Pregnancy before, during, or after the diagnosis of
      melanoma does not appear to influence 5-year survival rates. Exposure to OCs or
      HRT does not appear to increase the risk of melanoma.

PMID- 9759674
TI  - Dermatoses of pregnancy.
AB  - Several reported dermatoses of pregnancy have not survived the scrutiny of time
      and thus including them in current classification schemes does not serve any
      useful purpose. This review resolves issues in the existing conflicting
      literature.

PMID- 9759676
TI  - Vulvodynia and its differential diagnoses.
AB  - Vulvodynia is the symptom of chronic vulvar discomfort characterized by the
      patient's complaint of burning and sometimes stinging or rawness. It is a
      multifactorial problem in which no single etiologic factor or pathogenetic
      mechanism has been identified. Patients with vulvodynia exhibit several features
      of neuropathic pain, such as allodynia, hyperalgesia, dysesthesia, and chronic
      pain in the absence of ongoing noxious stimuli. The treatment of vulvodynia has,
      in the past, focused on irradicating suspected infective causes, such as human
      papillomavirus, with varying success. More recently, approaches mimicking the
      therapy of other chronic pain syndromes, eg, the use of low-dose antidepressants,
      has met with some success. There is a need for uniformity in terminology and
      therapeutic approach, epidemiologic studies, and controlled trials to advance our
      management of this problem.

PMID- 9759675
TI  - Vulvar dermatoses: lichen sclerosus, lichen planus, and vulval dermatitis/lichen
      simplex chronicus.
AB  - In our vulvar specialty clinic at Oxford Radcliffe Hospital (Oxford, UK),
      dermatoses are frequently seen. A recent survey of new patients showed that
      lichen sclerosus was the most commonly diagnosed vulvar dermatosis; approximately
      one third of the women had this disorder. Vulvar dermatitis was observed in 20%
      to 25% of new patients, but lichen planus was rare. Differences were observed in
      treatment outcomes for patients with vulvar dermatoses, such as lichen sclerosus
      and lichen planus, versus those with dermatologic disorders affecting the vulva,
      such as psoriasis and eczema.

PMID- 9759677
TI  - Benign vulvar tumors.
AB  - Benign tumors of the vulva, although relatively uncommon, are often referred to
      dermatologists for evaluation and treatment. The clinical features of benign
      tumors may overlap with malignant neoplasms, and therefore, a biopsy is often
      necessary to make a definitive diagnosis. This article discusses benign tumors of
      the vulva that are not associated with infectious agents and presents their
      classification according to cell of origin.

PMID- 9759678
TI  - Vulvar intraepithelial neoplasia and carcinoma.
AB  - This report describes the classification, clinical profile, etiology, and
      management of high-grade squamous vulvar intraepithelial-neoplasia (VIN). Recent
      studies have better defined the progressive potential of high-grade VIN and the
      relationship of such lesions to squamous vulvar carcinoma. The histologic
      classification and descriptions have undergone significant refinement over the
      past decade. The increasing use of more conservative therapeutic approaches to
      high-grade VIN has demanded greater expertise in clinical evaluation to ensure
      invasive disease is not missed or undertreated.

PMID- 9759679
TI  - Clinical approach to scleroderma.
AB  - Systemic sclerosis (SSc) is a heterogenous disease with a morbidity and mortality
      that varies widely. Nonetheless, the future clinical course of an individual
      patient can be estimated based on the severity of skin and internal organ
      involvement within the first several years of the disease. Patients with limited
      cutaneous SSc (ISSc) have skin thickening below the elbows or knees and may have
      face and neck involvement. Patients with this subtype of SSc have Raynaud's
      phenomenon, digital ulcers, and esophageal dysfunction. Significant morbidity and
      mortality arises in those patients with ISSc who develop interstitial lung
      disease or pulmonary artery hypertension. Patients with diffuse cutaneous SSc
      (dSSc) have skin thickening above the elbows and knees or on the trunk. These
      patients have a more abrupt onset of disease, often with constitutional symptoms
      and arthalgias. Severe heart, lung, gut, and renal involvement, if it occurs,
      tends to develop within the first 5 years of disease, especially within the first
      several years. Patients with significant internal organ involvement have a poorer
      prognosis than patients who do not. The goals of the initial history and physical
      and laboratory examinations are to classify the type of scleroderma as ISSc or
      dSSc, to estimate disease duration, and to define the extent and severity of
      organ involvement. Treatment of SSc is organ based. Treatment may reduce
      morbidity associated with Raynaud's phenomenon, digital ulcers, esophageal
      dysmotility, esophageal reflux, gut dysmotility, arthralgias, myositis, and
      pulmonary artery hypertension. Therapy may stabilize lung function in patients
      with interstitial lung disease with alveolitis and stabilize renal function in
      patients with renal crisis. The overall prognosis for patients with SSc appears
      to be improving. Patients with early dSSc should be considered for enrollment
      onto protocol testing of potential disease-modifying therapies.

PMID- 9759680
TI  - Dermatologic lupus: Hopkins Lupus Cohort.
AB  - Dermatologic manifestations are among the most common signs of systemic lupus
      erythematosus (SLE). The Hopkins Lupus Cohort study is a prospective study in
      which patients with SLE are seen on a quarterly basis for measurement of disease
      activity, laboratory tests, and assessment of morbidity and quality of life. This
      cohort has allowed unique insights into the epidemiologic factors of SLE, the
      presentation of dermatologic lupus, and morbidity, all of which are presented in
      this report. In addition, the dermatologic signs of antiphospholipid antibody
      syndrome (APS) are reviewed. Approaches to treatment of dermatologic lupus and
      APS are discussed.

PMID- 9759681
TI  - Executive summary of the clinical guidelines on the identification, evaluation,
      and treatment of overweight and obesity in adults.
AB  - An estimated 97 million adults in the United States are overweight or obese, a
      condition that substantially raises their risk of morbidity from hypertension,
      dyslipidemia, type 2 diabetes, coronary heart disease, stroke, gallbladder
      disease, osteoarthritis, sleep apnea and respiratory problems, and endometrial,
      breast, prostate, and colon cancers. Higher body weights are also associated with
      increases in all-cause mortality. Obese individuals may also suffer from social
      stigmatization and discrimination. As a major contributor to preventive death in
      the United States today, overweight and obesity pose a major public health
      challenge.

PMID- 9759682
TI  - Concepts of fever.
AB  - If asked to define fever, most physicians would offer a thermal definition, such
      as "fever is a temperature greater than...." In offering their definition, many
      would ignore the importance of the anatomic site at which temperature
      measurements are taken, as well as the diurnal oscillations that characterize
      body temperature. If queried about the history of clinical thermometry, few
      physicians could identify the source or explain the pertinacity of the belief
      that 98.6 degrees F (37.0 degrees C) has special meaning vis-a-vis normal body
      temperature. Fewer still could cite the origin of the thermometer or trace the
      evolution of modern concepts of clinical thermometry. Although many would have
      some knowledge of the fundamentals of thermoregulation and the role played by
      exogenous and endogenous pyrogens in the induction of fever, few would have more
      than a superficial knowledge of the broad biological activities of pyrogenic
      cytokines or know of the existence of an equally complex and important system of
      endogenous cryogens. A distinct minority would appreciate the obvious paradoxes
      inherent in an enlarging body of data concerned with the question of fever's
      adaptive value. The present review considers many of these issues in the light of
      current data.

PMID- 9759683
TI  - Calcium antagonists and mortality risk in men and women with hypertension in the
      Framingham Heart Study.
AB  - BACKGROUND: Several recent studies have suggested that calcium antagonist drugs,
      which are widely used for the treatment of hypertension, are associated with
      increased risk of cardiovascular disease. These studies have cast doubts on the
      long-term safety of calcium antagonists. OBJECTIVE: To examine the association of
      calcium antagonist use with mortality in subjects with hypertension followed up
      in the Framingham Heart Study. SUBJECTS AND METHODS: We stratified 3539 subjects
      (mean+/-SD age, 64+/-13 years) from the Framingham Heart Study who had
      hypertension at routine clinic examinations, according to the use of calcium
      antagonists and presence of coronary heart disease at the baseline examination.
      At each follow-up examination (every 2-4 years), subjects were reclassified with
      regard to the use of calcium antagonists. The end point of the study was all
      cause mortality. Hazard ratios and 95% confidence intervals associated with the
      use of calcium antagonists were obtained using Cox proportional hazards
      regression models. RESULTS: There were 970 deaths during follow-up. Hazard ratios
      for mortality associated with the use of calcium antagonists were 0.93 (95%
      confidence interval, 0.72-1.21; P=.59) for subjects with hypertension without
      coronary heart disease, and 0.92 (95% confidence interval, 0.69-1.24; P=.58) for
      those with coronary heart disease at baseline. All models were adjusted for age,
      sex, current smoking, systolic and diastolic blood pressure, use of beta
      blockers, and use of other antihypertensive medications. CONCLUSIONS: In this
      cohort of 3539 subjects with hypertension there were no differences in mortality
      among subjects with hypertension using a calcium antagonist compared with those
      who were not. Results were similar among subjects with hypertension with and
      without coronary heart disease. The results of ongoing long-term, randomized
      clinical trials will provide more definitive data on the safety of calcium
      antagonists.

PMID- 9759684
TI  - Renal failure in multiple myeloma: presenting features and predictors of outcome
      in 94 patients from a single institution.
AB  - BACKGROUND: Twenty percent of patients with multiple myeloma (MM) have renal
      failure. OBJECTIVE: To analyze the presenting features, the response to therapy,
      and the factors associated with renal function recovery and survival in 94
      patients with MM and renal failure. PATIENTS AND METHODS: Medical records of
      patients from our institution with MM and renal failure diagnosed between January
      1969 and December 1994 were reviewed. The statistical methods consisted of Kaplan
      Meier survival curves, the log-rank test, logistic regression analysis, and the
      Cox proportional hazards model for survival analysis. RESULTS: Renal failure was
      observed in 94 (22.2%) of 423 patients. Patients with renal failure had more
      advanced disease than the others. Patients with renal failure had a lower
      response rate to chemotherapy than those with normal renal function (39% vs 56%;
      P<.001). However, when patients dying within the first 2 months of treatment were
      excluded, no significant differences in the response rate were found between
      patients with renal failure and those with normal renal function. Renal function
      recovery was observed in 26% of patients. Serum creatinine level (<354 micromol/L
      [<4 mg/dL]), serum calcium level (> or =2.88 mmol/L [> or = 11.5 mg/dL]), and
      amount of proteinuria (< 1 g/24 h) were associated with renal function recovery.
      Patients who recovered renal function had a median survival of 28 months vs 4
      months for those with nonreversible renal failure (P<.001). In the multivariate
      analysis, only serum creatinine level (P=.003) and response to chemotherapy
      (P<.001) were correlated with survival. CONCLUSIONS: Renal failure was present in
      almost one fourth of patients with MM. Patients with reversible renal failure had
      longer survival than those not recovering renal function. When patients dying
      within the first 2 months of treatment were excluded, the response rate was not
      affected by renal function. Factors associated with renal function recovery were
      degree of renal failure, presence of hypercalcemia, and amount of proteinuria.
      Response to chemotherapy and severity of renal failure were the only independent
      factors associated with survival.

PMID- 9759685
TI  - Association of physical activity and human sleep disorders.
AB  - BACKGROUND: It is generally believed that exercise exerts a beneficial effect on
      the quality of sleep. However, most studies regarding exercise and sleep have
      been concerned with the influence of exercise on sleep architecture and
      efficiency, and not on its effects in the prevention and treatment of sleep
      disorders. Moreover, epidemiological evidence of the benefits of exercise on
      sleep are limited. OBJECTIVE: To investigate the influence of moderate exercise
      or physical activity on self-reported sleep disorders among a randomly selected
      population of adults. SUBJECTS AND METHODS: Study subjects were participants in
      the Tucson Epidemiological Study of Obstructive Airways Disease who in the 12th
      survey completed health questionnaires that included several questions on
      physical exercise and sleep disorders. Sleep disorders were classified as
      disorders in maintaining sleep, excessive daily sleepiness, nightmares, and any
      sleep disorder. Six questions regarding exercise and physical activity were
      asked. Analyses were performed using multivariate logistic regression models with
      selected measures of sleep disorders as dependent variables and measures of
      exercise and physical activity as the independent or predictor variables.
      RESULTS: There were 319 men and 403 women included in the analyses. The results
      showed that more women than men reported participating in a regular exercise
      program and having sleep symptoms of disorders in maintaining sleep and
      nightmares and that more men than women did regular vigorous activity and walking
      at a brisk pace for more than 6 blocks per day. Both men and women had
      significantly reduced risk of disorders in maintaining sleep associated with
      regular activity at least once a week, participating regularly in an exercise
      program, and walking at a normal pace for more than 6 blocks per day. Reduced
      risk of any sleep disorder was associated with regular activity at least once a
      week, and for men, walking at a brisk pace for more than 6 blocks. Among women
      increases in age also reduced the risk of nightmares. CONCLUSIONS: These data
      provide additional evidence that a program of regular exercise may be a useful
      therapeutic modality in the treatment of patients with sleep disorders.

PMID- 9759686
TI  - National patterns and predictors of beta-blocker use in patients with coronary
      artery disease.
AB  - BACKGROUND: Prior studies suggest underuse of beta-blockers in patients with
      coronary artery disease, but these studies have been based on selected
      populations of recently hospitalized patients. OBJECTIVE: To describe national
      patterns and determinants of beta-blocker use in the ambulatory setting. METHODS:
      We analyzed 11745 visits by patients with coronary artery disease to randomly
      selected, office-based physicians in the National Ambulatory Medical Care Surveys
      for 1980, 1981, 1985, and 1989 through 1996. We used multiple logistic regression
      to determine the independent effect of sociodemographic and clinical factors on
      beta-blocker use. OUTCOME MEASURE: Beta-blocker use at patient visits. RESULTS:
      Beta-blocker use was reported in only 20.9% of office visits by patients with
      coronary artery disease and no strong contraindications between 1993 and 1996. In
      multivariate analyses, age younger than 75 years, residence in the Northeast, and
      visits to cardiologists and internists compared with family and general
      practitioners predicted greater use of beta-blocker therapy. White race and
      private insurance also were significant predictors of beta-blocker use between
      1980 and 1996. Longitudinal analyses revealed a significant decline in beta
      blocker use from 1980 to 1990, followed by a gradual increase in recent years.
      CONCLUSIONS: Beta-blockers appear to be underused in ambulatory patients with
      coronary artery disease. Our data suggest that nonclinical factors may influence
      rates of use, indicating the need for closer scrutiny of variations in physician
      prescribing practices.

PMID- 9759687
TI  - Underuse of venous thromboembolism prophylaxis for general surgery patients:
      physician practices in the community hospital setting.
AB  - BACKGROUND: Venous thromboembolism is a common complication of surgery. Although
      surveys of physician self-reported practices have suggested near universal
      support for routine use of measures to prevent venous thromboembolism, medical
      record auditing has demonstrated underuse. OBJECTIVE: To assess physician
      practices of venous thromboembolism prophylaxis in the community hospital
      setting. METHODS: Retrospective review of the medical records from 20 hospitals
      in Oklahoma of 419 Medicare patients aged 65 years or older undergoing major
      abdominothoracic surgery between April 1 and December 31, 1995. Utilization rates
      of prophylaxis stratified according to patient risk for venous thromboembolism
      were measured. RESULTS: Prophylaxis measures were implemented for only 160 (38%)
      of 419 patients studied (95% confidence interval, 33%-43%). There was little
      variation in the use of prophylaxis based on the risk for venous thromboembolism.
      Only 97 (39%) of 250 patients (95% confidence interval, 33%-45%) at very high
      risk received any form of prophylaxis and of these 97, only 64 patients (66%)
      received appropriate measures (95% confidence interval, 56%-75%). CONCLUSIONS:
      Despite widely disseminated, evidence-based recommendations, venous
      thromboembolism prophylaxis is underused in Medicare patients undergoing major
      abdominothoracic surgery in community hospitals in Oklahoma.

PMID- 9759688
TI  - Factors related to in-hospital deaths in patients with tuberculosis.
AB  - BACKGROUND: Deaths from tuberculosis (TB) continue to occur despite the
      availability of effective antimicrobial agents. Multidrug resistance, human
      immunodeficiency virus (HIV) infection, and delayed therapy have been implicated.
      OBJECTIVE: To examine clinical factors associated with in-hospital death in
      patients with active TB. METHODS: A retrospective case-control study was
      performed on patients admitted to a government hospital in Johannesburg, South
      Africa, used as a referral center for patients with TB. Eighty patients admitted
      with TB who died during hospitalization were matched with 80 similar patients
      with TB who survived hospitalization. Clinical, demographic, and radiological
      characteristics of each group were compared. RESULTS: In-hospital fatalities were
      associated with female sex (P=.01), lower admission hemoglobin level (P<.01), and
      weight (P<.01), and a trend to more extensive infiltrative patterns on chest
      radiographs. Multidrug resistance, extrapulmonary disease, and HIV infection were
      unexpectedly not related to in-hospital mortality. High mortality in the first
      weeks of admission suggested that late presentation was a major factor for in
      hospital death. The HIV-infected participants in the study showed less drug
      resistance than HIV-negative patients (P=.07), equivalent extents of infiltrative
      patterns on chest radiographs, but much less cavitation and fibrosis (P<.01).
      CONCLUSIONS: Clinical predictors of early mortality from TB included anemia, low
      body weight, and extensive infiltrates, while multidrug resistance and HIV
      infection were not significant factors. Previous exposure to TB and delayed
      presentation may have influenced our findings. Since patients present late in
      their illness, aggressive case finding would be important in controlling TB in
      this population.

PMID- 9759689
TI  - Trends in infectious disease hospitalizations in the United States, 1980-1994.
AB  - BACKGROUND: A recent study concluded that between 1980 and 1992, deaths from
      infectious diseases increased 58%. This article explores trends in infectious
      diseases as a cause of hospitalization. METHODS: We analyzed data from the
      National Hospitalization Discharge Survey for 1980 through 1994 using a
      previously developed approach to evaluate infectious diseases in data coded
      according to the International Classification of Diseases, Ninth Revision.
      RESULTS: Between 1980 and 1994, the rate of hospitalizations in the United States
      declined approximately 33%; hospitalizations occurred at a rate of 133+/-5 per
      1000 US population (35 million+/-1 million discharges) in 1994. The rate of
      hospitalization for infectious diseases declined less steeply--12% during this
      interval--resulting in an increased proportion of hospitalizations because of
      infectious diseases. In 1994, the rate of hospitalizations for infectious
      diseases was 15.4+/-0.7 per 1000 US population (4.0 million+/-0.2 million
      discharges). The fatality rate associated with hospitalizations for infectious
      diseases increased from 1.9%+/-0.1% to 4.0%+/-0.3%, attributable to increased
      hospitalizations of elderly persons and an increased fatality rate among those
      younger than 65 years. Among selected categories, hospitalizations for human
      immunodeficiency virus infections and acquired immunodeficiency syndrome,
      prosthetic device infections, sepsis, and mycosis increased substantially, and
      hospitalizations for upper respiratory tract infections, pelvic inflammatory
      disease, and oral infections declined sharply. Hospitalizations for lower
      respiratory tract infections constituted 37% of all infectious disease
      hospitalizations in 1994. CONCLUSIONS: Considering hospitalizations as a
      dimension of the burden of infectious diseases involves an array of factors:
      secular trends in hospitalization, changing case management practices,
      demographic changes, and trends in the variety of infectious diseases themselves.
      Increases in the proportions of hospitalizations because of infectious diseases
      during years when hospitalizations for all causes were decreasing reflect an
      increasing burden of infectious diseases in the United States between 1989 and
      the mid-1990s.

PMID- 9759690
TI  - Superwarfarin poisoning.
AB  - BACKGROUND: Superwarfarin sodium exposure or poisoning is a growing public health
      problem. There were 5133 reported cases of superwarfarin exposure and poisoning
      in 1988 and 13 423 cases in 1995. Cases may be associated with accidental
      exposure, suicide attempts, or Munchausen syndrome, and may be difficult to
      diagnose. PATIENTS AND METHODS: Patients from northern Wisconsin with
      superwarfarin exposure or poisoning were examined at a tertiary referral center
      in rural Wisconsin to determine what led to their exposure and to review the
      clinical manifestations, diagnosis, treatment, and prevention of superwarfarin
      poisoning. RESULTS: Eleven cases satisfied the criteria for superwarfarin
      exposure or poisoning. All 7 children included in the study had accidentally
      ingested superwarfarin, 2 adults had Munchausen syndrome, and 1 teenager and 1
      adult had attempted suicide using superwarfarin. Nine of the 11 cases had taken
      brodifacoum. The patients who had accidentally ingested superwarfarin or
      attempted suicide using it were easily diagnosed, while diagnosis was markedly
      delayed for the 2 patients with Munchausen syndrome. Full reversal of
      anticoagulation was quickly achieved in the cases of accidental ingestion and
      attempted suicide. We examined and treated the patients with Munchausen syndrome
      for months before establishing a diagnosis and fully reversing the
      anticoagulation. None of the patients in our study died of superwarfarin
      poisoning. CONCLUSIONS: Superwarfarin exposure or poisoning is a growing public
      health problem that should be part of the differential diagnosis of patients who
      present with a coagulopathy consistent with vitamin K deficiency in the absence
      of coumadin therapy, liver disease, or the use of an inhibitor, and whose
      conditions do not resolve with large doses of parenteral vitamin K1 therapy.

PMID- 9759691
TI  - Microalbuminuria in nondiabetic adults: relation of blood pressure, body mass
      index, plasma cholesterol levels, and smoking: The Gubbio Population Study.
AB  - BACKGROUND: Evidence exists that cardiovascular risk factors influence
      progression toward end-stage renal failure. We tested the hypothesis that in
      nondiabetic middle-aged adults without macroalbuminuria, cardiovascular risk
      factors are related to urinary albumin excretion and prevalence of
      microalbuminuria, a sign of early nephropathy. METHODS: Cross-sectional analysis
      of data for 1567 participants in The Gubbio Population Study (677 men and 890
      women), aged 45 to 64 years, without macroalbuminuria, without diabetes mellitus,
      and with fasting plasma glucose levels of less than 7.8 mmol/L (140 mg/ dL). Data
      collection included albumin and creatinine excretion in timed overnight urine
      collection; levels of fasting plasma cholesterol, glucose, triglycerides,
      creatinine, and uric acid; creatinine clearance; red blood cell sodium-lithium
      countertransport; blood pressure; weight; height; medical history; smoking
      status; and alcohol intake. Urinary albumin excretion and prevalence of
      microalbuminuria were the dependent variables. RESULTS: Blood pressure, plasma
      cholesterol levels, smoking, and body mass index significantly related to urinary
      albumin excretion and prevalence of microalbuminuria. In analyses with control
      for multiple variables, relative risk for microalbuminuria (urinary albumin
      excretion, 20-199 microg/min) in men and women was 2.51 and 1.62, respectively,
      with 18 mm Hg higher (1 SD) systolic blood pressure; 2.25 and 2.10, respectively,
      with 1.0-mmol/L (40 mg/dL) higher plasma cholesterol level; 1.99 and 1.91,
      respectively, for smokers vs nonsmokers; and 1.83 and 1.33, respectively, with 4
      kg/m2 higher body mass index. Findings were similar for microalbuminuria defined
      as urinary albumin excretion of at least 25 microg/dL glomerular filtration rate.
      CONCLUSION: Major cardiovascular risk factors are independent correlates of
      microalbuminuria in nondiabetic middle-aged adults.

PMID- 9759692
TI  - Hospital-acquired pressure ulcers: risk factors and use of preventive devices.
AB  - BACKGROUND: Pressure ulcers are a frequent complication of bed rest. We examined
      risk factors for hospital-acquired pressure ulcers, the use of preventive
      devices, and the impact of case-mix adjustments on between-ward comparisons.
      METHODS: We conducted 3 cross-sectional surveys in a teaching hospital of 2373
      patients who had no pressure ulcer on admission. We assessed the presence of
      pressure ulcer, dates of admission and ulcer occurrence, hospital ward, patient
      age and sex, appetite and route of nutrition, surgery during stay,
      hospitalization for fracture, comorbidities, use of low-pressure devices (special
      mattresses, cushions, and pressure-reducing beds), and the Norton Pressure Ulcer
      Prediction score (physical condition, mental condition, activity, mobility, and
      incontinence). RESULTS: Two hundred forty-seven new pressure ulcers occurred (5.7
      per 1000 person-days). In multivariate analysis, the risk for pressure ulcer
      increased with age (risk gradient across 5 categories was 1:4.5; P<.001) and
      Norton score (across 5 categories, risk gradient was 30-fold; P<.001); other risk
      factors (all relative risks, 1.5-1.8; P<.002) were hospitalization for fracture,
      surgical intervention, reduced appetite, and nasogastric tube or intravenous
      nutrition. Adjustment for case mix substantially modified differences between
      hospital wards. Use of preventive devices was associated with Norton score, but
      not all high-risk patients benefited. CONCLUSIONS: Pressure ulcers were seen in
      every 10th hospitalized adult. Patient age and Norton score were the strongest
      risk factors for pressure ulcers. Use of preventive devices was suboptimal.
      Adjustment for case mix is essential if pressure ulcer incidence is to be used as
      an indicator of quality of care.

PMID- 9759693
TI  - Ischemic colitis and sumatriptan use.
AB  - Sumatriptan succinate, a serotonin-1 (5-hydroxytryptamine-1) receptor agonist, is
      an antimigraine drug that is reported to act by selectively constricting
      intracranial arteries. Recently, vasopressor responses that are distinct from the
      cranial circulation have been demonstrated to occur in the systemic, pulmonary,
      and coronary circulations. Cases have been published of coronary vasospasm,
      myocardial ischemia, and myocardial infarction occurring after sumatriptan use.
      We report on the development of 8 serious cases of ischemic colitis in patients
      with migraine treated with sumatriptan.

PMID- 9759694
TI  - First-generation vs second-generation antihistamines.

PMID- 9759695
TI  - Upper extremity DVT: what is the risk?

PMID- 9759696
TI  - Glioblastoma multiforme presenting as asymptomatic hyperprolactinemia.

PMID- 9759697
TI  - Dermatology education for internists.

PMID- 9759698
TI  - Adherence and effectiveness of highly active antiretroviral therapy.

PMID- 9759699
TI  - Combining volume-weighted mean nuclear volume with Gleason score and clinical
      stage to predict more reliably disease outcome of patients with prostate cancer.
AB  - BACKGROUND: Various criteria for patients with prostate cancer have been reported
      to be of prognostic value, and we have reported that estimates of volume-weighted
      mean nuclear volume (MNV), developed by Gundersen and Jensen based on a
      stereological technique, accurately predict the prognosis of prostate cancer.
      However, all of these studies were conducted on cases in a single institution,
      and it has remained unclear whether MNV calculations obtained at one institution
      apply to cases at another institution. In attempting to solve this problem, we
      made a prognostic index (P.I.) based on data from one hospital, and tested
      whether these data could be used to predict the prognosis of patients at another
      hospital. MATERIALS AND METHODS: A retrospective, multivariate prognostic study
      of 195 patients with prostate cancer, diagnosed at Kyoto University Hospital and
      treated conservatively, indicated that clinical stage, Gleason score, and MNV
      were all significantly correlated with the prognosis of patients with prostate
      cancer. From the relative strengths of these prognostic factors in a multivariate
      analysis, the following P.I. was constructed: P.I. = Clinical stage x 1.8040 +
      Gleason score x 1.5245 + MNV x 2.3162 (the constants correspond to the risk ratio
      estimated by Cox analysis). The P.I. was calculated for 104 patients with
      prostate cancer diagnosed at Shizuoka City Hospital and treated conservatively
      for analysis of disease-specific survival. RESULTS: The prognostic index ranged
      from 3.841-16.142. Using the median value of 12.5 as a cutoff point, a clear
      separation of cases with poor and favorable prognosis was achieved (P < 0.0001,
      observation period: 1-167 months). CONCLUSIONS: The results of this study suggest
      that estimates of MNV can be evaluated at multiple institutions with the use of
      P.I. calculation. Furthermore, combining estimates of MNV with Gleason score and
      clinical stage predicts most powerfully disease outcome of patients with prostate
      cancer.

PMID- 9759700
TI  - Effect of dual inhibition of 5-alpha-reductase and aromatase on spontaneously
      developed canine prostatic hypertrophy.
AB  - BACKGROUND: Our aim was to assess the effect of dual inhibition of 5-alpha
      reductase and aromatase on prostate glands. METHODS: We investigated the
      morphological changes in the prostate gland and the changes in the hormonal
      environment after administration of finasteride and arimidex to intact canine
      specimens. The study consisted of four groups: a 5-alpha-reductase only group
      (5RI only, n = 5); a 5RI plus aromatase-inhibitor combination group (5RI + ARI
      combination, n = 5); a BPH control group (n = 3); and a castration control group
      (n = 3). Finasteride (1 mg/kg/day) and the same dose of arimidex were orally
      administered for 80 days. RESULTS: In the 5RI group, a significant decrease in
      the serum dihydrotestosterone (DHT) level was found, and prostatic volume was
      significantly decreased. However, significant increases in serum testosterone (T)
      and DHT levels were observed, with a concomitant increase in prostatic volume in
      the 5RI + ARI combination group. Morphometric analysis showed that
      histopathological findings in the 5RI + ARI combination group were similar to
      those in the BPH control group. CONCLUSIONS: Dual inhibition of 5-alpha-reductase
      and aromatase resulted in a significant increase in prostate volume, accompanied
      by a 3-10-fold increase in serum testosterone levels and a significant increase
      in testicular volume.

PMID- 9759702
TI  - Regressive changes in finasteride-treated human hyperplastic prostates correlate
      with an upregulation of TGF-beta receptor expression.
AB  - BACKGROUND: Prostatic atrophy has been documented histologically as a consequence
      of finasteride action on human hyperplastic prostates. An increase in apoptotic
      rates has also been reported in androgen-deprived hyperplastic prostates.
      Transforming growth factor beta (TGF-beta) signaling is implicated in apoptotic
      cell death. TGF-betas have been detected in normal and diseased human prostate.
      In the normal prostate, TGF-beta acts as a predominantly negative growth
      regulator. TGF-beta signaling receptors TbetaRI and TbetaRII have been shown to
      be negatively regulated by androgens. METHODS: We studied the histological
      changes in 9 selected finasteride-treated patients with benign prostatic
      hyperplasia (BPH), and analyzed the levels of expression and localization of TGF
      beta receptor types TbetaRI and TbetaRII in these patients as compared to
      selected BPH controls. RESULTS: The prostatic epithelial compartment seemed to be
      a primary target site for finasteride action, since we observed moderate to
      severe glandular atrophy after 4-6 months of treatment. TGF-beta receptors were
      upregulated in treated cases. We assessed a twofold increase in TbetaRII mRNA
      levels in treated cases as compared to controls. An increase in both TbetaRI and
      TbetaRII at the protein level by immunostaining was observed, which also provided
      a helpful means for detecting glands undergoing regression. CONCLUSIONS: We
      conclude that finasteride may modulate the TGF-beta signaling system to promote
      changes leading to apoptosis of epithelial cells and prostatic glandular atrophy.

PMID- 9759701
TI  - Effects of long-term treatment with Serenoa repens (Permixon) on the
      concentrations and regional distribution of androgens and epidermal growth factor
      in benign prostatic hyperplasia.
AB  - BACKGROUND: The n-hexane lipido-sterol extract of Serenoa repens (LSESr,
      Permixon, Pierre Fabre Medicament, Castres, France), a phytotherapeutic agent
      used in the treatment of benign prostatic hyperplasia (BPH), has a multisite
      mechanism of action including inhibition of types 1 and 2 5alpha-reductase and
      competitive binding to androgen receptors in prostatic cells. Here, the response
      of testosterone (T), dihydrotestosterone (DHT), and epidermal growth factor (EGF)
      in BPH tissue of patients treated with LSESr (320 mg/day for 3 months) is
      analyzed. METHODS: BPH samples were sectioned in periurethral, subcapsular, and
      intermediate regions: in each region T, DHT, and EGF were determined by
      radioimmunoassay after purification on celite columns or Sep-pak C18 cartridges.
      RESULTS: In the untreated group, T, DHT, and EGF presented the highest
      concentrations in the periurethral region (615 +/- 62 (SE) pg/g tissue, 7,317 +/-
      551 pg/g tissue, and 20.9 +/- 3.3 ng/g tissue, respectively) with respect to the
      peripheral subcapsular region (425 +/- 45 pg/g tissue, 4,215 +/- 561 pg/g tissue,
      and 10.8 +/- 1.4 ng/g tissue, respectively). In the LSESr-treated group, a
      statistically significant reduction was observed, mainly in the periurethral
      region of DHT (2,363 +/- 553 pg/g tissue, P < 0.001) and EGF (6.98 +/- 2.48 ng/g
      tissue, P < 0.01), with increased T values (1,023 +/- 101 pg/g tissue, P <
      0.001). CONCLUSIONS: The decrease of DHT and the rise of T in BPH tissue of
      patients treated with Permixon confirms the capacity of this drug to inhibit in
      vivo 5alpha-reductase in human pathological prostate. A marked decrease of EGF,
      associated with DHT reduction, was also observed. These biochemical effects,
      similar to those obtained with finasteride, are particularly evident in the
      periurethral region, whose enlargement is responsible for urinary obstruction,
      with respect to the subcapsular region. A possible speculation is that the
      preferential reduction of DHT and EGF content in the periurethral region is
      involved in the clinical improvement of the obstructive symptoms in BPH during
      LSESr therapy.

PMID- 9759703
TI  - L6 monoclonal antibody binds prostate cancer.
AB  - BACKGROUND: Radioimmunotherapy (RIT) is a promising new modality for targeted,
      systemic delivery of radionuclides specifically to sites of androgen-independent
      metastatic prostate cancer. To be effective, RIT requires an antibody with
      specificity for malignant cells and appropriate pharmacokinetics in the body.
      METHODS: Specific binding of the L6 monoclonal antibody to prostate cancer cell
      lines or cell lysates was determined by enzyme-linked immunoabsorbent assay
      (ELISA), solid-phase radioimmunoassay, and immunofluorescent staining.
      Biodistribution, tumor uptake, and whole body and blood clearances of 125I-L6
      were determined in nude mice bearing human prostate cancer xenografts. RESULTS:
      The L6 monoclonal antibody showed strong binding to the lysates of PC3 and DU145
      prostate cancer cell lines, and 66% binding to live PC3 cells. The L6 antibody
      specifically targeted prostate cancer in PC3 and DU145-tumored nude mice, where
      approximately 10% of the injected dose of 125I-L6 bound to prostate cancer. Low
      normal organ uptake was found, and the blood clearances were similar in each
      group of tumored mice. CONCLUSIONS: The L6 monoclonal antibody targets human
      prostate cancer xenografts in nude mice and has low-normal organ uptake.
      Therefore, further study of the radiolabeled L6 monoclonal antibody for RIT of
      prostate cancer is warranted.

PMID- 9759704
TI  - Expression of the aryl hydrocarbon receptor (AhR) and the aryl hydrocarbon
      receptor nuclear translocator (ARNT) in fetal, benign hyperplastic, and malignant
      prostate.
AB  - BACKGROUND: Androgen-dependent tissue has been reported to be affected by
      chemical ligands of the aryl hydrocarbon receptor (AhR), a ligand-activated
      transcription factor, which heterodimerizes with the aryl hydrocarbon receptor
      nuclear translocator protein (ARNT). METHODS: Fetal (n = 3), benign hyperplastic
      (BPH) (n = 10), and carcinomatous (CaP) (n = 19) prostate tissues were analyzed
      using immunohistochemistry. Western blot analysis was used to confirm the
      identity of the recognized proteins. RESULTS: Immunoblotting of enriched
      prostatic epithelial cells (EC) and stromal cells revealed constitutive
      expression of bands at around 110 kDa and 90 kDa, using anti-AhR and anti-ARNT,
      respectively. Immunohistology of the fetal specimens revealed heterogeneous
      cytoplasmic and nuclear AhR expression of immature EC and mesenchymal cells.
      Constitutive expression of AhR (primarily cytoplasmic) and ARNT (nuclear and
      cytoplasmic) by the majority of adult basal and secretory EC, CaP, and smooth
      muscle cells was confirmed in situ. The most intense anti-AhR/-ARNT reactivity
      was found on smooth muscle cells, followed by EC and fibrocytes. Secretory BPH-EC
      revealed significantly decreased AhR expression when compared to normal tissue
      segments. By contrast, anti-AhR reactivity was frequently increased in the more
      dedifferentiated tumor areas. CONCLUSIONS: These findings suggest that an
      undefined physiologic AhR ligand(s) as well as environmental factors may exert
      effects on EC and smooth muscle cells in the prostate through binding to these
      receptors.

PMID- 9759706
TI  - New concept of BPH: PCAR theory.
AB  - BACKGROUND: A new concept of the pathophysiology of benign prostatic hyperplasia
      (BPH), based upon the presumed circle area ratio (PCAR) theory, is described.
      METHODS: The PCAR is the ratio of the area of the maximum horizontal section of
      the prostate by transrectal sonography to the area of a presumed circle of which
      the circumference is equal to the circumference of the maximum horizontal
      section. This evaluates how closely the shape of the section approaches a circle.
      RESULTS: A clear borderline was found at a PCAR of 0.75 in the postvoiding
      residual urine volume (PVR) in many cases of BPH. Cases with the PCAR below this
      level almost entirely showed a PVR below 30 ml, while cases with the PCAR over
      this level demonstrated a wide distribution of PVR. CONCLUSIONS: Such a variety
      of PVR in cases with the PCAR over 0.75 could be explained by the difference of
      the elasticity of the surgical capsule (peripheral zone) in each case, which was
      confirmed by a stress-strain test on extirpated specimens from the capsule at
      surgery. We developed a new clinical parameter called the prostatic pressure
      coefficient (PPC) to check elasticity, by means of a special balloon catheter
      inserted into the prostatic urethra.

PMID- 9759705
TI  - Characteristics of nonneoplastic human prostate tissue transplanted into nude
      mice.
AB  - BACKGROUND: Prostate tumors are characterized by sex hormone-associated growth
      and mesenchymal-epithelial interactions. This study was conducted to establish an
      ex vivo system where human prostate tissue could be maintained for a certain
      period under conditions resembling the in vivo situation in man to provide an
      experimental tool for investigation of prostate disease. METHODS: Human prostate
      tissues (peripheral zone and transition zone) obtained by total cystectomy were
      transplanted into the subcutis of male KSN nude mice for up to 24 weeks without
      exogenous hormonal manipulation. RESULTS: Transplants could be maintained, and
      although they showed several histological alterations, such as cystic dilation,
      basal-cell hyperplasia, and squamous-cell metaplasia, many retained a nearly
      normal appearance for the entire 24-week duration. Immunohistochemically,
      androgen receptors were strongly positive in the nuclei of glandular epithelial
      cells. Prostate-specific antigen (PSA) and prostatic acid phosphate (PAP) (both
      from DAKO, Glostrup, Denmark), were also expressed in the cytoplasm. The
      proportion of cells expressing proliferating cell nuclear antigen (PCNA) was not
      related to the period of transplantation and did not differ between the
      peripheral and transition zones. CONCLUSIONS: The results clearly demonstrate
      that human prostate tissues transplanted into nude mice can maintain their
      morphological and biological characteristics for up to 24 weeks. This provides a
      simple and useful tool for basic research into human prostate neoplasia.

PMID- 9759708
TI  - Wanted: a voice for the life sciences.

PMID- 9759707
TI  - New sensitive discovery histoculture model for growth-inhibition studies in
      prostate cancer and BPH.
AB  - BACKGROUND: A new, total-immersion three-dimensional histoculture (TIH) method
      was developed to evaluate growth of tissue containing a mixture of benign
      prostate hyperplasia (BPH) and prostate cancer in vitro. METHODS: Efficacy of
      inhibitors, such as genistein, was determined by measuring 3H-thymidine
      incorporation per microgram protein. Inhibitory effects obtained in TIH were
      compared to those in sponge-gel supported histoculture (SSH). RESULTS: 3H
      thymidine incorporation was 2-5-fold higher in tissue cultured in TIH than in
      SSH. The average inhibition by genistein at a concentration of 18 JIM was 73% in
      TIH, vs. 31% in SSH. TIH also appeared to be more sensitive, since the lowest
      concentration of genistein that significantly inhibited growth of BPH mixed with
      prostate cancer tissue was 2.3 IJM, while in SSH the lowest concentration was 9.2
      F,M. Although the within-assay coefficient of variation (CV) was similar for both
      TIH and SSH, the between-assay CV was better in TIH. CONCLUSIONS: These data
      suggest that TIH can be used as a discovery model for screening and evaluating
      inhibitors of prostate tissue growth in vitro.

PMID- 9759709
TI  - Panel urges caution on genetic testing for mental disorders.

PMID- 9759710
TI  - US gene-therapy proposals come under fire.

PMID- 9759711
TI  - Biology federation urged to widen focus.

PMID- 9759712
TI  - UK life science students seek better deal.

PMID- 9759713
TI  - France to set up co-ordinating committee.

PMID- 9759714
TI  - Restrict genetic susceptibility tests.

PMID- 9759715
TI  - Protein breakdown. Ubiquitous deja vu.

PMID- 9759717
TI  - Isotope astrophysics. Sorting stardust.

PMID- 9759716
TI  - Developmental biology. Birds of a feather flock together.

PMID- 9759718
TI  - Behavioural genetics. Worming out social secrets.

PMID- 9759719
TI  - Membrane fusion. SNARE the rod, coil the complex.

PMID- 9759720
TI  - Origins of life. Buried beginnings.

PMID- 9759721
TI  - Otto Wichterle (1913-98)

PMID- 9759722
TI  - Gray's greyness.

PMID- 9759723
TI  - Arsenic poisoning of Bangladesh groundwater.

PMID- 9759724
TI  - Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 A
      resolution.
AB  - The evolutionarily conserved SNARE proteins and their complexes are involved in
      the fusion of vesicles with their target membranes; however, the overall
      organization and structural details of these complexes are unknown. Here we
      report the X-ray crystal structure at 2.4 A resolution of a core synaptic fusion
      complex containing syntaxin-1 A, synaptobrevin-II and SNAP-25B. The structure
      reveals a highly twisted and parallel four-helix bundle that differs from the
      bundles described for the haemagglutinin and HIV/SIV gp41 membrane-fusion
      proteins. Conserved leucine-zipper-like layers are found at the centre of the
      synaptic fusion complex. Embedded within these leucine-zipper layers is an ionic
      layer consisting of an arginine and three glutamine residues contributed from
      each of the four alpha-helices. These residues are highly conserved across the
      entire SNARE family. The regions flanking the leucine-zipper-like layers contain
      a hydrophobic core similar to that of more general four-helix-bundle proteins.
      The surface of the synaptic fusion complex is highly grooved and possesses
      distinct hydrophilic, hydrophobic and charged regions. These characteristics may
      be important for membrane fusion and for the binding of regulatory factors
      affecting neurotransmission.

PMID- 9759725
TI  - Abiotic nitrogen reduction on the early Earth.
AB  - The production of organic precursors to life depends critically on the form of
      the reactants. In particular, an environment dominated by N2 is far less
      efficient in synthesizing nitrogen-bearing organics than a reducing environment
      rich in ammonia. Relatively reducing lithospheric conditions on the early Earth
      have been presumed to favour the generation of an ammonia-rich atmosphere, but
      this hypothesis has not been studied experimentally. Here we demonstrate mineral
      catalysed reduction of N2, NO2- and NO3- to ammonia at temperatures between 300
      and 800 degrees C and pressures of 0.1-0.4 GPa-conditions typical of crustal and
      oceanic hydrothermal systems. We also show that only N2 is stable above 800
      degrees C, thus precluding significant atmospheric ammonia formation during hot
      accretion. We conclude that mineral-catalysed N2 reduction might have provided a
      significant source of ammonia to the Hadean ocean. These results also suggest
      that, whereas nitrogen in the Earth's early atmosphere was present predominantly
      as N2, exchange with oceanic, hydrothermally derived ammonia could have provided
      a significant amount of the atmospheric ammonia necessary to resolve the early
      faint-Sun paradox.

PMID- 9759726
TI  - Object-based attention in the primary visual cortex of the macaque monkey.
AB  - Typical natural visual scenes contain many objects, which need to be segregated
      from each other and from the background. Present theories subdivide the processes
      responsible for this segregation into a pre-attentive and attentive system. The
      pre-attentive system segregates image regions that 'pop out' rapidly and in
      parallel across the visual field. In the primary visual cortex, responses to pre
      attentively selected image regions are enhanced. When objects do not segregate
      automatically from the rest of the image, the time-consuming attentive system is
      recruited. Here we investigate whether attentive selection is also associated
      with a modulation of firing rates in area V1 of the brain in monkeys trained to
      perform a curve-tracing task. Neuronal responses to the various segments of a
      target curve were simultaneously enhanced relative to responses evoked by a
      distractor curve, even if the two curves crossed each other. This indicates that
      object-based attention is associated with a response enhancement at the earliest
      level of the visual cortical processing hierarchy.

PMID- 9759727
TI  - An analgesia circuit activated by cannabinoids.
AB  - Although many anecdotal reports indicate that marijuana and its active
      constituent, delta-9-tetrahydrocannabinol (delta-9-THC), may reduce pain
      sensation, studies of humans have produced inconsistent results. In animal
      studies, the apparent pain-suppressing effects of delta-9-THC and other
      cannabinoid drugs are confounded by motor deficits. Here we show that a brainstem
      circuit that contributes to the pain-suppressing effects of morphine is also
      required for the analgesic effects of cannabinoids. Inactivation of the rostral
      ventromedial medulla (RVM) prevents the analgesia but not the motor deficits
      produced by systemically administered cannabinoids. Furthermore, cannabinoids
      produce analgesia by modulating RVM neuronal activity in a manner similar to, but
      pharmacologically dissociable from, that of morphine. We also show that
      endogenous cannabinoids tonically regulate pain thresholds in part through the
      modulation of RVM neuronal activity. These results show that analgesia produced
      by cannabinoids and opioids involves similar brainstem circuitry and that
      cannabinoids are indeed centrally acting analgesics with a new mechanism of
      action.

PMID- 9759728
TI  - Paired-spike interactions and synaptic efficacy of retinal inputs to the
      thalamus.
AB  - In many neural systems studied in vitro, the timing of afferent impulses affects
      the strength of postsynaptic potentials. The influence of afferent timing on
      postsynaptic firing in vivo has received less attention. Here we study the
      importance of afferent spike timing in vivo by recording simultaneously from
      ganglion cells in the retina and their targets in the lateral geniculate nucleus
      of the thalamus. When two spikes from a single ganglion-cell axon arrive within
      30 milliseconds of each other, the second spike is much more likely than the
      first to produce a geniculate spike, an effect we call paired-spike enhancement.
      Furthermore, simultaneous recordings from a ganglion cell and two thalamic
      targets indicate that paired-spike enhancement increases the frequency of
      synchronous thalamic activity. We propose that information encoded in the high
      firing rate of an individual retinal ganglion cell becomes distributed among
      several geniculate neurons that fire synchronously. Because synchronous
      geniculate action potentials are highly effective in driving cortical neurons, it
      is likely that information encoded by this strategy is transmitted to the next
      level of processing.

PMID- 9759729
TI  - Drosophila oocyte localization is mediated by differential cadherin-based
      adhesion.
AB  - In a Drosophila follicle the oocyte always occupies a posterior position among a
      group of sixteen germline cells. Although the importance of this cell arrangement
      for the subsequent formation of the anterior-posterior axis of the embryo is well
      documented, the molecular mechanism responsible for the posterior localization of
      the oocyte was unknown. Here we show that the homophilic adhesion molecule DE
      cadherin mediates oocyte positioning. During follicle biogenesis, DE-cadherin is
      expressed in germline (including oocyte) and surrounding follicle cells, with the
      highest concentration of DE-cadherin being found at the interface between oocyte
      and posterior follicle cells. Mosaic analysis shows that DE-cadherin is required
      in both germline and follicle cells for correct oocyte localization, indicating
      that germline-soma interactions may be involved in this process. By analysing the
      behaviour of the oocyte in follicles with a chimaeric follicular epithelium, we
      find that the position of the oocyte is determined by the position of DE-cadherin
      expressing follicle cells, to which the oocyte attaches itself selectively. Among
      the DE-cadherin positive follicle cells, the oocyte preferentially contacts those
      cells that express higher levels of DE-cadherin. On the basis of these data, we
      propose that in wild-type follicles the oocyte competes successfully with its
      sister germline cells for contact to the posterior follicle cells, a sorting
      process driven by different concentrations of DE-cadherin. This is, to our
      knowledge, the first in vivo example of a cell-sorting process that depends on
      differential adhesion mediated by a cadherin.

PMID- 9759730
TI  - A function for lipoxygenase in programmed organelle degradation.
AB  - Membrane-enclosed organelles, a defining characteristic of eukaryotic cells, are
      lost during differentiation of specific cell types such as reticulocytes (an
      intermediate in differentiation of erythrocytes), central fibre cells of the eye
      lens, and keratinocytes. The degradation of these organelles must be tightly
      regulated with respect to both the time of activation and the specificity of
      membrane degradation. The expression of 15-lipoxygenase (15-LOX) peaks in
      reticulocytes immediately before organelle degradation. Here we show that 15-LOX
      integrates into the membranes of various organelles, allowing release of proteins
      from the organelle lumen and access of proteases to both lumenal and integral
      membrane proteins. In addition, by sparing the plasma membrane, 15-LOX shows the
      required specificity for organellar membranes. Thus, the action of 15-LOX
      provides a mechanism by which the natural degradation process can be explained.
      This conclusion is supported by our finding that lipoxygenase expression in the
      eye lens is restricted to the region at which organelle degradation occurs.

PMID- 9759731
TI  - A protein conjugation system essential for autophagy.
AB  - Autophagy is a process for the bulk degradation of proteins, in which cytoplasmic
      components of the cell are enclosed by double-membrane structures known as
      autophagosomes for delivery to lysosomes or vacuoles for degradation. This
      process is crucial for survival during starvation and cell differentiation. No
      molecules have been identified that are involved in autophagy in higher
      eukaryotes. We have isolated 14 autophagy-defective (apg) mutants of the yeast
      Saccharomyces cerevisiae and examined the autophagic process at the molecular
      level. We show here that a unique covalent-modification system is essential for
      autophagy to occur. The carboxy-terminal glycine residue of Apg12, a 186-amino
      acid protein, is conjugated to a lysine at residue 149 of Apg5, a 294-amino-acid
      protein. Of the apg mutants, we found that apg7 and apg10 were unable to form an
      Apg5/Apg12 conjugate. By cloning APG7, we discovered that Apg7 is a ubiquitin-E1
      like enzyme. This conjugation can be reconstituted in vitro and depends on ATP.
      To our knowledge, this is the first report of a protein unrelated to ubiquitin
      that uses a ubiquitination-like conjugation system. Furthermore, Apg5 and Apg12
      have mammalian homologues, suggesting that this new modification system is
      conserved from yeast to mammalian cells.

PMID- 9759732
TI  - Retinoid-X receptor signalling in the developing spinal cord.
AB  - Retinoids regulate gene expression through the action of retinoic acid receptors
      (RARs) and retinoid-X receptors (RXRs), which both belong to the family of
      nuclear hormone receptors. Retinoids are of fundamental importance during
      development, but it has been difficult to assess the distribution of ligand
      activated receptors in vivo. This is particularly the case for RXR, which is a
      critical unliganded auxiliary protein for several nuclear receptors, including
      RAR, but its ligand-activated role in vivo remains uncertain. Here we describe an
      assay in transgenic mice, based on the expression of an effector fusion protein
      linking the ligand-binding domain of either RXR or RAR to the yeast Gal4 DNA
      binding domain, and the in situ detection of ligand-activated effector proteins
      by using an inducible transgenic lacZ reporter gene. We detect receptor
      activation in the spinal cord in a pattern that indicates that the receptor
      functions in the maturation of limb-innervating motor neurons. Our results reveal
      a specific activation pattern of Gal4-RXR which indicates that RXR is a critical
      bona fide receptor in the developing spinal cord.

PMID- 9759733
TI  - Position and orientation of the globular domain of linker histone H5 on the
      nucleosome.
AB  - It is essential to identify the exact location of the linker histone within
      nucleosomes, the fundamental packing units of chromatin, in order to understand
      how condensed, transcriptionally inactive chromatin forms. Here, using a site
      specific protein-DNA photo-crosslinking method, we map the binding site and the
      orientation of the globular domain of linker histone H5 on mixed-sequence chicken
      nucleosomes. We show, in contrast to an earlier model, that the globular domain
      forms a bridge between one terminus of chromatosomal DNA and the DNA in the
      vicinity of the dyad axis of symmetry of the core particle. Helix III of the
      globular domain binds in the major groove of the first helical turn of the
      chromatosomal DNA, whereas the secondary DNA-binding site on the opposite face of
      the globular domain of histone H5 makes contact with the nucleosomal DNA close to
      its midpoint. We also infer that helix I and helix II of the globular domain of
      histone H5 probably face, respectively, the solvent and the nucleosome. This
      location places the basic carboxy-terminal region of the globular domain in a
      position from which it could simultaneously bind the nucleosome-linking DNA
      strands that exit and enter the nucleosome.

PMID- 9759734
TI  - Taking knowledge from bench to bank.

PMID- 9759735
TI  - Prevention and treatment of occupational mental disorders.

PMID- 9759736
TI  - Impact of new criteria for diabetes on pattern of disease.

PMID- 9759737
TI  - NSAIDs and Helicobacter pylori: therapeutic options.

PMID- 9759738
TI  - Relevance of the first seizure.

PMID- 9759740
TI  - Are all infections with Escherichia coli O157 associated with cattle?

PMID- 9759739
TI  - Ethical issues in genetics of mental disorders.

PMID- 9759741
TI  - Framingham at 50.

PMID- 9759742
TI  - Epileptology of the first-seizure presentation: a clinical,
      electroencephalographic, and magnetic resonance imaging study of 300 consecutive
      patients.
AB  - BACKGROUND: Prognosis and treatment of the first seizure depends on
      identification of a specific epilepsy syndrome, yet patients with first seizures
      are generally regarded as a homogeneous group. We studied whether it is possible
      to diagnose specific epilepsy syndromes promptly by use of standard clinical
      methods, electroencephalography (EEG) and magnetic resonance imaging (MRI).
      METHODS: 300 consecutive adults and children presented with unexplained seizures.
      We systematically collected clinical data from patients and witnesses, and
      attempted to obtain an EEG within 24 h of the seizure. Where the EEG was
      negative, a sleep-deprived EEG was done. MRI was done electively. FINDINGS: A
      generalised or partial epilepsy syndrome was clinically diagnosed in 141 (47%)
      patients. Subsequent analysis showed that only three of these clinical diagnoses
      were incorrect. Addition of the EEG data enabled us to diagnose an epilepsy
      syndrome in 232 (77%) patients. EEG within 24 h was more useful in diagnosis of
      epileptiform abnormalities than later EEG (51 vs 34%). Neuroimaging showed 38
      epileptogenic lesions, including 17 tumours. There were no lesions in patients
      for whom generalised epilepsy was confirmed by EEG. Our final diagnoses were:
      generalised epilepsy (23% of patients); partial epilepsy (58%); and unclassified
      (19%). INTERPRETATION: An epilepsy syndrome can be diagnosed in most first
      seizure patients. Ideally, an EEG should be obtained within 24 h of the seizure
      followed by a sleep deprived EEG if necessary. MRI aids diagnosis and should be
      done for all patients except for those with idiopathic generalised epilepsies and
      for children with benign rolandic epilepsy.

PMID- 9759743
TI  - Diabetes in older adults: comparison of 1997 American Diabetes Association
      classification of diabetes mellitus with 1985 WHO classification.
AB  - BACKGROUND: We aimed to compare the prevalence of abnormal glucose tolerance
      identified by the 1985 WHO and the 1997 American Diabetes Association (ADA)
      diagnostic categories based on information collected in the Cardiovascular Health
      Study, an epidemiological study of elderly people. METHODS: We measured glucose
      concentrations during fasting and 2 h after a 75 g oral glucose-tolerance test in
      participants aged 65-100 years in the Cardiovascular Health Study. From a 1989
      cohort, we analysed the glucose measurements of 4515 individuals without a
      previous diagnosis of diabetes and of 262 additional measurements from an African
      American cohort recruited in 1992-93. FINDINGS: In the 1989 cohort, the
      prevalence of untreated diabetes with ADA diagnostic fasting criteria was 7.7%
      versus a prevalence of 14.8% by the WHO criteria. In the African-American cohort,
      the prevalence of untreated diabetes was 2.7% with ADA criteria and 11.8% with
      WHO criteria. 3509 (77.7%) of the 4515 participants in the 1989 cohort had normal
      glucose concentrations according to ADA fasting criteria, compared with 2401
      (53.2%) according to WHO criteria. In the African-American cohort, the
      corresponding numbers were 239 (91.2%) versus 153 (58.4%). All differences in
      prevalence of abnormal glucose tolerance between ADA and WHO classifications were
      significant (p<0.0001). INTERPRETATION: Among elderly individuals, there was a
      significant difference in the prevalence of diabetes identified by the WHO
      diagnostic criteria based on oral glucose-tolerance test and the ADA fasting
      criteria. Consequently, many individuals currently classified as non-diabetic
      according to ADA criteria would previously have had a diagnosis of diabetes
      according to WHO criteria. Longitudinal studies are needed to assess the value of
      the criteria in the identification of individuals at increased risk of diabetes
      associated chronic complications.

PMID- 9759745
TI  - Randomised trial of impact of school mental-health programme in rural Rawalpindi,
      Pakistan.
AB  - BACKGROUND: A school mental-health programme has been developed as a component of
      the community mental-health programme in Rawalpindi, Pakistan. It has the
      objective of improving the understanding of disorders of mental health in the
      rural community. We aimed to assess the impact of a school mental-health
      programme on the awareness of schoolchildren, their parents, friends who were not
      attending school, and neighbours. METHODS: We chose two secondary schools for
      boys and two for girls that were similar in terms of size, staff-pupil ratio, and
      drop-out rates. 100 children aged 12-16 years (25 girls and 25 boys in each of
      the study and control groups), 100 parents (one for each child), 100 friends who
      did not attend school (one for each child), and 100 neighbours (one for each
      child) were given a 19-item questionnaire before and after the study group had
      had a 4-month programme of mental-health education. The maximum score for the
      questionnaire was 16 points. FINDINGS: Before the school mental-health programme
      the awareness of mental-health issues was poor (mean score 5.7-7.6) in the four
      groups of participants. In the study group there was a significant improvement in
      the mean scores after the school programme in the schoolchildren (mean
      improvement 7.6 [95% CI 6.7-8.5], p<0.01), their parents (5.3 [4.5-6.1], p<0.01),
      friends (5.1 [4.1-6.1], p<0.01), and neighbours (3.4 [2.6-4.2], p<0.01). In the
      control group the difference in awareness was significant only in schoolchildren
      (1.5 [0.5-2.3], p=0.01) and their friends (0.8 [0.3-1.3], p<0.01).
      INTERPRETATION: The school programme succeeded in improving awareness of mental
      health in schoolchildren and the community. The schoolchildren were receptive to
      the programme, and shared their new understanding with family, friends, and
      neighbours. Mental-health planners who wish to improve community awareness of
      mental health, particularly in areas with low literacy rates, should consider
      setting up school mental-health programmes.

PMID- 9759744
TI  - Randomised controlled trial of Helicobacter pylori eradication in patients on non
      steroidal anti-inflammatory drugs: HELP NSAIDs study. Helicobacter Eradication
      for Lesion Prevention.
AB  - BACKGROUND: The effect of Helicobacter pylori in patients receiving non-steroidal
      anti-inflammatory drugs (NSAIDs) is unclear. We investigated the effects of H.
      pylori eradication in patients with current or previous peptic ulceration,
      dyspepsia, or both who continued to use NSAIDs. METHODS: 285 patients were
      randomly assigned omeprazole 20 mg, amoxycillin 1000 mg, and clarithromycin 500
      mg, twice daily (n=142, H. pylori eradication treatment), or omeprazole with
      placebo antibiotics (n=143, controls) for 1 week. All patients received
      omeprazole 20 mg once daily for 3 weeks until endoscopy, and, if the ulcer was
      not healed, 40 mg once daily until repeat endoscopy at 8 weeks. Ulcer-free
      patients with mild dyspepsia continued NSAIDs but not antiulcer treatment. We
      investigated ulcers with endoscopy at 1, 3, and 6 months and with carbon-13
      labelled urea breath test at 3 months. FINDINGS: The estimated probability of
      being ulcer-free at 6 months was 0.56 (95% CI 0.47-0.65) on eradication treatment
      and 0.53 (0.44-0.62) on on control treatment (p=0.80). Time to treatment failure
      did not differ between groups for ulcers or dyspepsia alone, per-protocol
      analysis, or final H. pylori status. 66% (58-74) of the eradication group
      compared with 14% (8-20) of the control group had a final negative H. pylori
      result (p<0.001). Fewer baseline gastric ulcers healed among eradication
      treatment patients than among controls (72 vs 100% at 8 weeks, p=0.006).
      INTERPRETATION: H. pylori eradication in long-term users of NSAIDs with past or
      current peptic ulcer or troublesome dyspepsia led to impaired healing of gastric
      ulcers and did not affect the rate of peptic ulcers or dyspepsia over 6 months.

PMID- 9759747
TI  - Pulsating varicose veins.

PMID- 9759746
TI  - Absence of Oxalobacter formigenes in cystic fibrosis patients: a risk factor for
      hyperoxaluria.
AB  - BACKGROUND: Patients with cystic fibrosis have an increased risk of
      hyperoxaluria, and of subsequent nephrocalcinosis and calcium-oxalate
      urolithiasis. Oxalate homoeostasis is controlled, in part, by the intestinal
      bacterium, Oxalobacter formigenes. The loss of this bacterium from the gut flora
      is associated with an increased risk of hyperoxaluria and calcium-oxalate
      urolithiasis. We investigated whether the absence of O. formigenes and the
      presence of hyperoxaluria are correlated in cystic fibrosis (CF) patients.
      METHODS: Stool specimens from 43 patients with CF aged 3-9 years and from 21
      similarly aged healthy volunteers were examined for O. formigenes by culture and
      DNA analysis. At the same time, 24 h urine samples were collected and analysed
      for oxalate and other factors that promote or inhibit stone formation. FINDINGS:
      15 (71%) of 21 healthy volunteers but only seven (16%) of 43 CF patients were
      colonised with O. formigenes. Detection of O. formigenes in six of these seven
      patients required DNA-based identification, suggesting low numbers of colony
      forming units, and the CF patient with normal numbers of O. formigenes was the
      only one of the 43 patients who had not been treated with antibiotics. All seven
      CF patients colonised with O. formigenes had normal urinary oxalate levels, but
      19 (53%) of 36 patients not colonised with O. formigenes were hyperoxaluric, with
      the most severe hyperoxaluria occurring in young patients. INTERPRETATION:
      Absence of O. formigenes from the intestinal tract of CF patients appears to lead
      to increased absorption of oxalate, thereby increasing the risk of hyperoxaluria
      and its complications (eg, nephrocalcinosis, urolithiasis). Prolonged widespread
      use of antibiotics, and alterations of the gastrointestinal tract that occur in
      CF, may induce a permanent decolonisation in CF patients.

PMID- 9759748
TI  - Atorvastatin and gemfibrozil for protease-inhibitor-related lipid abnormalities.

PMID- 9759749
TI  - Protease inhibitors and adipocyte differentiation in cell culture.

PMID- 9759750
TI  - Expression of sequence variants of endogenous retrovirus RGH in particle form in
      multiple sclerosis.

PMID- 9759751
TI  - Thyrotoxicosis incidence in Switzerland and benefit of improved iodine supply.

PMID- 9759752
TI  - Eradication of human T-lymphotropic virus type 1 by allogeneic bone-marrow
      transplantation.

PMID- 9759753
TI  - Low blood pressure and early death of elderly people with dementia.

PMID- 9759754
TI  - Thrombotic thrombocytopenic purpura after stenting and ticlopidine.

PMID- 9759755
TI  - Action of anticardiolipin and antibodies to beta2-glycoprotein-I on trophoblast
      proliferation as a mechanism for fetal death.

PMID- 9759756
TI  - Rate of caesarean section and pregnancy outcome in women lawyers.

PMID- 9759757
TI  - Nerve growth factor promising in diabetic neuropathy...and in HIV-1-related
      neuropathy.

PMID- 9759758
TI  - Green coffee beans may yield new class of anti-HIV-1 agents.

PMID- 9759759
TI  - High-tech and low-tech predictors of stroke risk.

PMID- 9759761
TI  - Careful smiles around the Blue Mosque in Turkey.

PMID- 9759760
TI  - Martin Schechter: fighting the politicians with science.

PMID- 9759762
TI  - Landmine ratification allows international law to go ahead.

PMID- 9759763
TI  - Catalonia makes plans to help addicted doctors.

PMID- 9759764
TI  - Stigma of mental illness. Foreword.

PMID- 9759766
TI  - Mistaken identity.

PMID- 9759765
TI  - Can the stigma of mental illness be changed?

PMID- 9759767
TI  - UK mental health policy can alter the stigma of mental illness.

PMID- 9759768
TI  - Stigma of manic depression: a psychologist's experience.

PMID- 9759769
TI  - Stigma and disease: changing paradigms.

PMID- 9759770
TI  - Cultural variation in the stigmatisation of mental illness.

PMID- 9759771
TI  - Stigma: what can psychiatrists do about it?

PMID- 9759772
TI  - Mental illness made public: ending the stigma?

PMID- 9759773
TI  - Access to the dead: the role of relatives in the aftermath of disaster.

PMID- 9759774
TI  - Peer review of grant applications.

PMID- 9759775
TI  - Peer review of grant applications.

PMID- 9759776
TI  - Peer review of grant applications.

PMID- 9759777
TI  - Peer review of grant applications.

PMID- 9759778
TI  - Cystic fibrosis and Young's syndrome.

PMID- 9759779
TI  - Cystic fibrosis and Young's syndrome.

PMID- 9759780
TI  - Diagnostic techniques for ventilator-associated pneumonia.

PMID- 9759781
TI  - Eclampsia studies in developing countries.

PMID- 9759782
TI  - Haemochromatosis and type 2 diabetes.

PMID- 9759783
TI  - Origins of BSE.

PMID- 9759784
TI  - ACE inhibitors and pneumonia.

PMID- 9759785
TI  - Decrease of blood pressure by ventrolateral medullary decompression in essential
      hypertension.

PMID- 9759786
TI  - Lupus-like syndrome associated with simvastatin.

PMID- 9759787
TI  - Oxyphilic parathyroid adenoma and lithium therapy.

PMID- 9759788
TI  - US transplant system.

PMID- 9759789
TI  - Patient recruitment in Helicobacter pylori drug trials.

PMID- 9759790
TI  - 12th World AIDS Conference.

PMID- 9759791
TI  - Intellectual property protection and pharmaceuticals.

PMID- 9759793
TI  - What prevents hospitalizations and relapse from asthma?

PMID- 9759794
TI  - A 7-year-old girl with cerebral palsy and multiple warts.

PMID- 9759795
TI  - Prevalence of sensitization to aeroallergens in California patients with
      respiratory allergy. Allergy Skin Test Project Team.
AB  - BACKGROUND: The number of allergy skin tests required to evaluate patients with
      respiratory allergy has recently been challenged by the managed care community.
      OBJECTIVES: The purpose of this study was to determine which aeroallergens are
      prevalent in patients with respiratory allergy (allergic rhinitis and bronchial
      asthma) in California. METHODS: Utilizing aeroallergens thought to be relevant
      from recent aerobiologic and botanic data, 141 allergic and 17 asymptomatic
      control subjects were tested for the prevalence of 103 allergens. A standardized
      prick puncture technique and standardized interpretation of wheal/flare responses
      were utilized using the same lot of allergen for 13 allergy practices distributed
      throughout California. Frequency curves based on prevalence were established to
      determine the number of tests required to give up to 90% of positive responses
      for tree, weed and grass pollen, mold spores, and miscellaneous allergens which
      included house dust mite, cat, dog, and cockroach allergens. RESULTS: Positive
      responses in allergic subjects for grasses ranged from 46% to 54%, for weeds 19%
      to 37%, and for trees 10% to 42%. For molds the range was from 11% to 22%. The
      response rate for Dermatophagoides pteronyssinus was 53%, for Dermatophagoides
      farinae 42%, for cat pelt 39% and cat hair 37%, for cockroach 23% and dog dander
      19%. Asymptomatic control subjects responded to only 4% of all allergens tested.
      Ninety percent of all positive tests required three miscellaneous allergens
      (house dust mite, cat, and cockroach), 9 molds, 2 grasses, 16 weeds, and 27 trees
      for a total of 57 allergens (56% of total tested). There was no clear
      relationship between locale and specific allergen response, probably related to
      the limited number of subjects tested and variability within the same geographic
      region. Several seldom tested tree and weed allergens showed a higher prevalence
      rate than several commonly tested for allergens. CONCLUSIONS: This preliminary
      study suggests that approximately 57 aeroalleroens might be adequate to detect
      90% of all positive responses in patients with respiratory allergy in California.
      This study was limited by subject number and variability between study sites. It
      is hoped a standardized model can be developed from this pilot study to
      definitively determine which aeroallergens are relevant in the United States.

PMID- 9759796
TI  - Evaluation of olopatadine, a new ophthalmic antiallergic agent with dual
      activity, using the conjunctival allergen challenge model.
AB  - BACKGROUND: An ophthalmic antiallergic agent with selective H1 antihistaminic and
      mast cell stabilizing properties has been developed. OBJECTIVES: To evaluate
      efficacy and safety, determine optimal concentration, and demonstrate onset and
      duration of action of this new drug, olopatadine. METHODS: This was a placebo
      controlled, randomized, double-masked, parallel-group, single-center study with
      five outpatient visits at least 7 days apart. Ninety-eight healthy, allergy
      positive, subjects with a recent history of active allergic conjunctivitis not
      receiving current treatment participated. Conjunctival allergen challenge (CAC)
      tests were performed on visits 1 and 2 to identify an allergen and concentration
      that consistently elicited signs and symptoms of allergic conjunctivitis. On
      visits 3, 4, and 5, CAC was performed 27 minutes, 8 hours, and 6 hours,
      respectively, after instillation of one drop of olopatadine (0.01%, 0.05%, 0.1%,
      or 0.15%) in one eye and placebo in the other. Both eyes were scored for the
      intensity of itching and redness at 3, 10, and 20 minutes after the CAC. RESULTS:
      All four concentrations of olopatadine were clinically and statistically superior
      to placebo in preventing ocular itching at all evaluations and preventing redness
      at most evaluations from immediately and 8 hours after drug administration. No
      drug-related adverse events were reported. The 0.1% concentration was found to be
      most effective. CONCLUSIONS: The results indicate that olopatadine ophthalmic
      solution is safe and effective in the treatment of allergic conjunctivitis, with
      the 0.1% concentration of olopatadine being optimal. The rapid onset and at least
      8 hour duration of action of olopatadine indicates that the drug can be used
      twice daily.

PMID- 9759797
TI  - Immunohistochemical characterization of cellular infiltrate in nasal polyp from
      aspirin-sensitive asthmatic patients.
AB  - BACKGROUND: The immunopathologic mechanism of nasal polyp in aspirin-sensitive
      asthma remains to be further defined. OBJECTIVE: To characterize the features of
      the inflammatory cellular infiltrate in the nasal polyp tissue from aspirin
      sensitive asthmatic patients. METHODS: We have taken nasal polyp tissue during
      nasal polyp resection from 13 aspirin-sensitive asthma, 6 allergic, and 12 non
      allergic subjects. Immunohistochemistry was employed to stain and enumerate the
      individual inflammatory cell types using monoclonal antibodies against tryptase
      (AA1) to identify mast cells, against secreted forms of eosinophil cationic
      protein (EG2), to identify activated eosinophils, against neutrophil elastase
      (NE) for neutrophils and against T cell surface markers (CD3) to identify total T
      cells. RESULTS: There were no significant differences in AA1 + cells among three
      groups (P>.05). EG2 + cells tended to be higher in ASA-sensitive asthmatic
      patients than in allergic and non-allergic subjects, but no statistical
      significance was observed. NE+ cells were found in most subjects of the three
      groups and their numbers were significantly higher in allergic subjects than in
      aspirin-sensitive asthma (P<.05). Some patients had CD3+ cells with no
      statistical significance among the three groups. Significant correlation was
      found in numbers between NE+ cell and AA1+ cell (r=.44, P=.01), and between NE+
      cell and EG2+ cell (r=.40, P=.02). CONCLUSION: These findings suggested that
      major effector cells such as mast cells and eosinophils might be placed in the
      center of the inflammatory response of nasal polyps, regardless of their
      association with aspirin sensitivity.

PMID- 9759798
TI  - A 3-month comparison of formoterol with terbutaline via turbuhaler. A placebo
      controlled study.
AB  - BACKGROUND AND AIM: Oxis Turbuhaler is a new dry powder formulation of long
      acting beta2-agonist formoterol. This study compared the efficacy and safety of
      regular use of the long-acting beta2-agonist formoterol and the short-acting
      terbutaline for 3 months in patients with asthma. METHOD: After 1-week run-in,
      343 patients received either formoterol 12 microg bid (F) (delivered dose of 9
      microg), terbutaline 500 microg qid (T) or placebo qid, in a parallel-group,
      double-blind, randomized manner. They had a mean of 61% of predicted forced
      expiratory volume in 1 second (FEV1) and a mean reversibility of 26%. Eighty-nine
      percent used inhaled corticosteroids. RESULTS: During run-in mean morning peak
      expiratory flow (PEF L/min) for F was 366 and 348 for T, and 344 for placebo (P).
      The F group improved morning PEF significantly compared with P (P = .0022) and T
      (P = .0001). Changes from run-in were + 18, -1.5, and +5 L/min after F, T, and P,
      respectively. The F group was statistically significantly better than P and T in
      increasing evening PEF and in reducing night-time asthma. The F and T
      statistically significantly reduced the use of rescue medication compared with P.
      The bronchodilating response to the study drug and to an additional 1.25 mg
      terbutaline was of the same magnitude before and throughout the study. No
      statistically significant treatment-by-time interaction was observed (P > .20).
      There were no adverse effects of clinical relevance. CONCLUSION: Formoterol
      Turbuhaler, 12 microg bid, was more effective than terbutaline Turbuhaler, 0.5 mg
      qid, and placebo. Regular use of formoterol or terbutaline did not significantly
      influence the response to additional inhalation of terbutaline.

PMID- 9759799
TI  - Theophylline inhibits the late asthmatic response to nighttime antigen challenge
      in patients with mild atopic asthma.
AB  - BACKGROUND: Inhaled antigen at night causes a more pronounced late asthmatic
      response (LAR) when compared with daytime challenges. Chronopharmacology with
      controlled-release theophylline given in the evening leads to a peak serum
      theophylline concentration (STC) in early morning which coincides with LAR that
      follows an evening challenge. OBJECTIVE: To evaluate the effect of controlled
      release theophylline given with the evening meal on the immediate asthmatic
      response (IAR) and LAR following nighttime antigen challenge in patients with
      mild atopic asthma. METHODS: To qualify, subjects underwent antigen
      bronchoprovocation by graded nebulization until the IAR (fall in FEV1 of > or
      =20%) occurred; spirometry was then measured hourly for 8 hours to establish the
      presence of LAR (fall in FEV1 > or =15%). After 2 weeks of randomized, double
      blind crossover treatment with either theophylline (target STC of 10 to 15 mg/L,
      (56 to 83 micromol/L)) or placebo, inhaled antigen challenge was performed at 10
      PM in each subject. FEV1 values were measured immediately and then hourly for 8
      hours following antigen challenge. RESULTS: Twelve subjects completed the study.
      During the placebo phase, the maximal fall in FEV1 during LAR was 39 +/- 3% (mean
      +/- SEM) compared with 31 +/- 4% fall during theophylline treatment phase (P =
      .01). A reduction in LAR occurred despite higher dose (P <.05) of inhaled antigen
      during theophylline phase, which would have been expected to result in a more
      pronounced LAR. Serum theophylline concentration at 8 AM on the day following
      antigen challenge was 9.6 +/- 1.1 mg/L (53 +/- 6 micromol/L). CONCLUSION:
      Nocturnal administration of controlled-release theophylline increases the
      tolerance to inhaled antigen and reduces severity of LAR. Because the LAR is
      linked to airway inflammation, these data support the possibility of
      antiinflammatory effects associated with theophylline use.

PMID- 9759800
TI  - Aspirin and paracetamol tolerance in patients with nimesulide-induced urticaria.
AB  - BACKGROUND: The administration of aspirin and other nonsteroidal anti
      inflammatory drugs in patients sensitive to nimesulide might be hazardous.
      OBJECTIVE: To assess the tolerance to both acetaminophen (paracetamol) and
      aspirin in patients with a history of urticaria induced by nimesulide. METHODS:
      Nine patients with a history of nimesulide intolerance were submitted to single
      blind, placebo-controlled peroral challenges with increasing doses of
      acetaminophen and aspirin. RESULTS: Acetaminophen was tolerated by all patients,
      whereas two experienced immediate systemic urticaria after the administration of
      125 mg of aspirin. CONCLUSION: Acetaminophen and aspirin are well tolerated by
      most nimesulide-sensitive patients. Since a minority of patients show aspirin
      sensitivity, tolerance of this agent should always be ascertained by properly
      performed peroral challenges.

PMID- 9759801
TI  - Behavioral and environmental factors associated with acute exacerbation of
      asthma.
AB  - BACKGROUND: The relapse rate following treatment for acute asthma is high. While
      previous studies have evaluated the utility of pulmonary function measurements to
      identify patients likely to relapse, the results are conflicting. The purpose of
      this study was to evaluate other correctable, risk factors that may be associated
      with relapse. PARTICIPANTS: Two hundred twenty-three patients treated in the
      emergency department during 1994, including those either admitted or discharged.
      METHODS: Patient interviews to identify behavioral and environmental risk factors
      for asthma exacerbation. Telephone contact and medical record review to determine
      incidence of relapse. RESULTS: Two hundred twenty-three patients were enrolled of
      whom follow-up data were available for 152 (68%). Twenty-one percent of the
      patients relapsed within 14 days. Relapse was associated with the lack of an
      identifiable primary care physician and inability to obtain discharge
      medications. There was no relationship between relapse and the use of a spacer,
      hypoallergenic pillow or mattress cover, cigarette smoking, the presence of pets
      in the home, or weekly carpet cleaning. CONCLUSION: Even following
      hospitalization for acute asthma, there is a significant relapse rate. Improving
      patients' access to primary care physicians and to appropriate medications may
      decrease the relapse rate. Although a significant portion of patients have
      behavioral and environmental risk factors for asthma exacerbation including
      cigarette smoking and failure to maintain a hypoallergenic environment, these
      factors are not associated with short-term relapse.

PMID- 9759803
TI  - IgE-sensitization to cellular and culture filtrates of fungal extracts in
      patients with atopic dermatitis.
AB  - BACKGROUND: Patients with atopic dermatitis may experience exacerbations of
      eczema triggered by various inflammatory stimuli. One mechanism may be IgE
      mediated reactions to dermatophytes since these patients are more likely to
      acquire skin infections with dermatophytes and may become sensitized. OBJECTIVE:
      This study investigates IgE-sensitization to fungi in patients with atopic
      dermatitis and compares the biologic activity of culture filtrates and cellular
      fungal extracts. The following allergen extracts were provided as culture
      filtrates and cellular extracts: Candida albicans, Fusarium moniliforme, and
      Penicillium notatum. In addition, Pityrosporum ovale and Trichophyton rubrum
      cultures were included in the test panel. METHODS: Fifteen patients with clinical
      findings suggesting dermatophytosis and 11 controls were selected. Each subject
      was tested by leukocyte histamine release and skin prick test to each fungal
      extract. The extracts were separated and reduced by sodium dodecylsulfate
      polyacrylamide gel electrophoresis and analyzed by IgE-immunoblotting with sera
      from all study subjects. RESULTS: Fourteen patients (93%) reacted to one or
      several fungal extracts by releasing histamine when challenged in vitro. By
      immunoblotting experiments, patient sera showed binding to a wide range of
      components in all extracts. Patient sera recognized allergenic components shared
      by culture filtrates and cellular extracts but with higher frequent and greater
      intensity in culture filtrates. Although culture filtrates generated more
      frequent and potent IgE-reactions than the cellular extracts, the difference was
      not statistically significant. Biologic potency was similar when evaluated by
      skin prick tests and leukocyte histamine release. CONCLUSION: Patients with
      atopic dermatitis may develop specific IgE-antibodies to a number of fungi as
      demonstrated by IgE-immunoblotting. In selected patients, fungi may trigger an
      IgE-mediated reaction that may contribute to the exacerbation of eczema.
      Approximately, one-half of the patients, however, produced IgE-antibodies to
      fungal (glyco)proteins without a significant histamine release or skin test
      response possibly because of nonspecific interaction with carbohydrate moieties
      on IgE and poor biologic activity of IgE antibodies directed to cross-reactive
      carbohydrate determinants of fungal glycoproteins. This warrants caution when
      interpreting clinical relevance of serologic measurements of fungal IgE
      antibodies.

PMID- 9759802
TI  - Exacerbation of premenstrual asthma caused by an oral contraceptive.
AB  - BACKGROUND: The relationship between sex hormones and asthma has not been
      clarified. Studies have suggested a potential beneficial effect of exogenous sex
      hormones and/or contraceptive pills on asthma in premenopausal females whereas
      the data for postmenopausal females are inconsistent. CASE REPORT: A 33-year-old
      woman suffering from asthma with premenstrual exacerbations had a stable course
      until she began taking oral contraceptives. At that time she experienced clinical
      deterioration of her asthma associated with decline of pulmonary function tests.
      No other precipitating factors were identified. After discontinuing the
      contraceptives, her condition returned to baseline. CONCLUSION: We found only two
      reports of worsening of asthma related to hormonal therapy (estrogen in one case,
      contraceptive pills in the other) in premenopausal women. Our report, together
      with these observations, suggests that in some premenopausal women exogenous sex
      hormones and/or contraceptive pills may, contrary to expected, produce
      exacerbation of asthma.

PMID- 9759804
TI  - Severe anaphylaxis from rifamycin SV.
AB  - BACKGROUND: Anaphylaxis to topical application of rifamycin SV, which is used
      topically in the fields of surgery and dermatology, is rare. METHODS: We report
      two cases of systemic reactions occurring after local administration of rifamycin
      (Rifocine, Gruppo Lepetit, Italy). Both of them needed repeated intermittent
      topical applications. Skin prick tests with Rifocine constituents were performed
      on our patients, and also on ten atopic and ten nonatopic subjects. Although an
      old investigative tool, Prausnitz-Kustner (P-K) test was also performed on one of
      the patient's spouses to show passive transfer and the IgE-mediated mechanism.
      RESULTS: Allergy assessment with skin tests on the patients were negative for
      aeroallergens, latex, and Rifocine constituents (except rifamycin SV). The
      patients' prick tests with rifamycin SV were positive, and the control subjects
      were negative. P-K testing was positive. CONCLUSION: Two case reports support the
      existence of IgE-mediated reactions to rifamycin SV. IgE-mediated anaphylactic
      reactions from rifamycin SV appear to be extremely rare.

PMID- 9759805
TI  - Association between giardiasis and allergy.
AB  - BACKGROUND: Previous studies have indicated that there may be an association
      between infection by the intestinal protozoan Giardia lamblia and the expression
      of allergic disease. OBJECT: We evaluated a group of children who attended the
      Outpatient Clinic of the Children's Hospital in Caracas, Venezuela, a group in
      which both allergic disease and giardiasis were common. METHODS: We performed
      feces examination and measured total and specific serum IgE (immunoglobulin E) in
      these children. RESULTS: We found that 70% of the children infected with G.
      lamblia presented symptoms of allergy, in contrast to 43% of the non-Giardia
      parasitized group (P <.05). In addition, the G. lamblia parasitized children
      showed significantly higher levels of total serum IgE (1194 IU/mL) than the non
      Giardia group (822 IU/mL) (P <.005). Children infected with G. lamblia showed
      higher levels of specific serum IgE antibody against food allergens compared both
      with the non-parasitized group (P <.0001) and children infected with parasites
      other than Giardia (P <.05). In contrast, IgE responses against the house dust
      mite Dermatophagoides pteronyssinus were similar in all the groups studied.
      CONCLUSIONS: These results reveal a clear relationship between giardiasis and
      allergy, possibly because infection by this protozoon enhances sensitization
      towards food antigens, due to increased antigen penetration through damaged
      intestinal mucosa.

PMID- 9759807
TI  - Anaphylaxis to rabbit: a case report.
AB  - BACKGROUND: While rabbits are common as pets, severe allergic reactions to
      domestic rabbits in homes are unusual. Typically, allergic manifestations are
      mild to moderate allergic rhinitis, conjunctivitis, pruritus and/or asthma in
      laboratory animal caretakers with frequent exposure. METHODS: We report an atopic
      child with a severe allergic reaction following inhalant exposure to a rabbit. We
      performed percutaneous skin tests and determined serum-specific IgE to commercial
      preparation of rabbit epithelium and extracts of rabbit fur and serum. RESULTS:
      Percutaneous skin test was positive to rabbit epithelium. The patient had
      elevated serum-specific IgE to rabbit epithelium and fur but not to rabbit serum.

PMID- 9759806
TI  - Relationships of race and socioeconomic status with prevalence, severity, and
      symptoms of asthma in Chicago school children.
AB  - BACKGROUND: Asthma mortality rates in Chicago are among the highest in the United
      States, with substantially greater rates in poor and minority populations. How
      much of the differential can be attributed to differences in prevalence versus
      severity or access to care has not been determined. OBJECTIVE: To examine rates
      of asthma prevalence, severity, and symptoms and to explore the relationships of
      these rates to race and socioeconomic status in a random sample of Chicago school
      children. METHODS: Self-administered survey. RESULTS: Overall, rates of asthma
      were higher than previously reported, with 16% of students in the stratified
      cluster random sample of 3,670 children in the 7th and 8th grades having had
      asthma. Prevalence rates were significantly higher in schools with >98% African
      Americans than in other schools, with the highest prevalence rates seen in
      African American schools in low income neighborhoods. Rates were associated with
      the percent of African American children in the school and with median income of
      the school's census tract. Relationships were most consistent with indices of
      more severe disease. CONCLUSIONS: Asthma prevalence is higher than previously
      noted, with rates greatest in minority and low income populations. Differences
      are more striking for measures of severity than for symptoms of wheezing, but are
      far less than previously reported differences in mortality, suggesting that
      additional factors, such as differential access to continuous health care, may be
      affecting high death rates from asthma in Chicago.

PMID- 9759808
TI  - Legg-Calve-Perthes disease in girls. A comparison of the results with those seen
      in boys.
AB  - We reviewed the records and roentgenograms of all patients with Legg-Calve
      Perthes disease who had been seen at our institution between 1940 and 1996. One
      hundred and five girls (122 hips) and 470 boys (531 hips) were identified. Thus,
      18 per cent of the 575 patients in the present series were girls. Seventeen (16
      per cent) of the girls and sixty-one (13 per cent) of the boys had bilateral
      involvement. Although more girls than boys had severe involvement of the femoral
      head and the lateral pillar, we could not detect a significant difference between
      the two groups with respect to the distribution of the involvement of the hips
      according to the system of Catterall or the lateral pillar classification (p >
      0.05, beta = 0.99). Serial roentgenograms that showed all four stages of the
      disease according to the system of Waldenstrom were available for fifty-two hips
      in girls and 184 hips in boys. A review of these roentgenograms revealed that the
      average ages of the girls at the stages of necrosis, fragmentation,
      reossification, and remodeling were 6.8, 7.3, 7.9, and 9.5 years, respectively,
      whereas the average ages of the boys were 6.8, 7.3, 7.9, and 9.9 years,
      respectively. Girls, however, had closure of the affected proximal femoral physis
      at an average age of 12.9 years, whereas boys had closure at an average age of
      15.8 years. Therefore, girls had a shorter potential period for remodeling of the
      femoral head (average, 3.4 years) compared with boys (average, 5.9 years). Sixty
      four girls (seventy-eight hips) and 363 boys (416 hips) had reached skeletal
      maturity by the time of the latest follow-up and were evaluated according to the
      system of Stulberg et al.; we could not detect a significant difference between
      boys and girls with respect to the distribution of the hips according to this
      system (p > 0.05, beta = 0.99). Although the numbers were too small for
      statistical analysis, our findings suggest that boys and girls who have the same
      Catterall or lateral pillar classification at the time of the initial evaluation
      can be expected to have similar outcomes according to the classification system
      of Stulberg et al.

PMID- 9759809
TI  - Levels of carbon dioxide in helmet systems used during orthopaedic operations.
AB  - The use of isolation helmets has gained popularity as a method of possible
      protection of the operating-room personnel from diseases that can be transmitted
      during operative procedures. However, the use of these systems has been
      associated with a variety of symptoms, including fatigue, diaphoresis, nausea,
      headache, and irritability. These symptoms have often been attributed to the
      mental stress of the operative procedure or the physical discomfort of the
      helmet. As far as we know, no manufacturers include the measured levels of carbon
      dioxide or the rate of air exchange of their helmet system. A possible common
      cause of discomfort with helmet systems is the level of carbon dioxide to which
      the person wearing the device is exposed. We measured the levels of carbon
      dioxide in four helmet systems from three different manufacturers during light
      exercise designed to approximate the exertion during an orthopaedic operation.
      All but one unit failed to meet the exposure limits recommended by the National
      Institute for Occupational Safety and Health and the Occupational Safety and
      Health Administration regarding exposure to carbon dioxide. One unit, the
      Stackhouse Freedom Aire self-contained system, did meet these standards, but the
      levels of carbon dioxide in this helmet were more than 1000 per cent greater than
      the ambient levels in air (440 parts per million compared with 4939 parts per
      million). Isolation systems must be evaluated carefully not only for comfort but
      also for the physiological effects caused by exposure to elevated levels of
      carbon dioxide. Operating-room personnel who use such systems should be aware
      that many of the physical symptoms that they experience may be associated with
      elevated levels of carbon dioxide.

PMID- 9759810
TI  - Survival analysis of hips treated with core decompression or vascularized fibular
      grafting because of avascular necrosis.
AB  - Avascular necrosis of the femoral head is a multifaceted process that leads to
      articular incongruity and subsequent osteoarthrosis of the joint. Clinicians
      concur that primary treatment should focus on preservation of the natural surface
      of the joint; however, there has not been a consensus on how best to accomplish
      this. While a number of therapeutic interventions have been reported, the
      efficacy has varied markedly and there have been few statistical comparisons. The
      purpose of the current study was to use statistical analysis to compare the
      results of two widely used procedures, vascularized fibular grafting (614 hips;
      480 patients) and core decompression (ninety-eight hips; seventy-two patients),
      for the treatment of avascular necrosis. The patients were stratified according
      to age and the stage of disease, and a survival analysis was performed with total
      hip arthroplasty as the end point for failure. None of the eleven hips that had
      Ficat stage-I disease needed a total joint replacement after being treated with
      either regimen. Analysis of the hips that had stage-II disease revealed rates of
      survival, at fifty months, of 65 per cent (twenty-eight of forty-three hips)
      after core decompression and 89 per cent (ninety-nine of 111 hips) after
      vascularized fibular grafting. For the hips that had Ficat stage-III disease, the
      rates of survival at fifty months were 21 per cent (ten of forty-seven hips)
      after core decompression and 81 per cent (405 of 500 hips) after vascularized
      fibular grafting. Among the hips that had Ficat stage-II or III disease, the rate
      of eventual total joint arthroplasty after vascularized fibular grafting was
      significantly lower than that after core decompression (p < 0.0001). The results
      indicate that the increased morbidity associated with vascularized fibular
      grafting is justified by the associated delay in or prevention of articular
      collapse in hips that have stage-II or III disease.

PMID- 9759811
TI  - Magnetic resonance imaging of articular cartilage in the knee. An evaluation with
      use of fast-spin-echo imaging.
AB  - The purpose of this study was to demonstrate that specialized magnetic resonance
      imaging provides an accurate assessment of lesions of the articular cartilage of
      the knee. Arthroscopy was used as the comparative standard. Eighty-eight patients
      who had an average age of thirty-eight years were evaluated with magnetic
      resonance imaging and subsequent arthroscopy because of a suspected meniscal or
      ligamentous injury. The magnetic resonance imaging was performed with a
      specialized sequence in the sagittal, coronal, and axial planes. Seven articular
      surfaces (the patellar facets, the trochlea, the femoral condyles, and the tibial
      plateaus) were graded prospectively on the magnetic resonance images by two
      independent readers with use of the 5-point classification system of Outerbridge,
      which was also used at arthroscopy. Six hundred and sixteen articular surfaces
      were assessed, and 248 lesions were identified at arthroscopy. Eighty-two
      surfaces had chondral softening; seventy-five, mild ulceration; fifty-three, deep
      ulceration, fibrillation, or a flap without exposure of subchondral bone; and
      thirty-eight, full-thickness wear. To simplify the statistical analysis, grades 0
      and 1 were regarded as disease-negative status and grades 2, 3, and 4 were
      regarded as disease-positive status. When the grades that had been assigned by
      reader 1 were used for the analysis, magnetic resonance imaging had a sensitivity
      of 87 per cent (144 of 166), a specificity of 94 per cent (424 of 450), an
      accuracy of 92 per cent (568 of 616), a positive predictive value of 85 per cent
      (144 of 170), and a negative predictive value of 95 per cent (424 of 446) for the
      detection of a chondral lesion. Interobserver variability was minimum, as
      indicated by a weighted kappa statistic of 0.93 (almost perfect agreement). With
      use of this readily available modified magnetic resonance imaging sequence, it is
      possible to assess all articular surfaces of the knee accurately and thereby
      identify lesions that are amenable to arthroscopic treatment.

PMID- 9759812
TI  - Total knee arthroplasty in patients receiving Workers' Compensation.
AB  - The poor outcomes in patients who have a low-back injury that was sustained while
      they were on the job have been well described in many studies. The purpose of the
      current study was to determine the influence of Workers' Compensation on the
      outcome of total knee arthroplasty in forty-two patients who had been managed
      between January 1980 and December 1993. There were thirty-two men and ten women,
      and the mean age at the time of the operation was forty-eight years (range,
      twenty-nine to sixty-eight years). These patients were directly matched with a
      group of forty-two patients who were not receiving compensation. The two groups
      were matched with regard to nine parameters: age, gender, obesity index,
      preoperative deformity in the coronal plane, preoperative level of symptoms,
      preoperative radiographic severity according to the criteria of Ahlback, method
      of fixation, number of previous procedures, and duration of follow-up. After a
      mean duration of follow-up of eighty months (range, forty-eight to 178 months),
      the patients who were receiving compensation had a mean Knee Society score of 64
      points (range, 25 to 100 points). Twelve (29 per cent) of the patients in this
      group had an excellent or good clinical result, and thirty (71 per cent) had a
      fair or poor result or had had a revision. The patients who were not receiving
      compensation had a mean Knee Society score of 93 points (range, 57 to 100 points)
      after a similar duration of follow-up. Thirty-seven patients (88 per cent) in
      this group had an excellent or good clinical result, and five (12 per cent) had a
      fair or poor result or had had a revision; the difference between the two groups
      with regard to fair or poor results and revisions was significant (p < 0.01).
      With the numbers available, no significant differences could be detected between
      the two groups with regard to objective measurements of range of motion and
      stability or with regard to radiographic alignment, the presence of radiolucent
      lines, or the shedding of beads. On the basis of our findings, we believe that
      surgeons should be aware that Workers' Compensation is one of several variables
      that may have an untoward influence on the perceived outcome of total knee
      arthroplasty.

PMID- 9759813
TI  - Postoperative mortality after total hip arthroplasty. An analysis of deaths after
      two thousand seven hundred and thirty-six procedures.
AB  - We retrospectively determined the prevalence and nature of mortality as many as
      ninety days after 2736 primary and revision total hip arthroplasties performed in
      2002 patients by one surgeon at a teaching hospital between January 1969 and
      December 1996. All but seventy-one of the patients had received prophylaxis
      against venous thromboembolic disease. There were no intraoperative deaths, and
      no events during the operation could be linked directly to postoperative
      mortality. Eight deaths (mortality rate, 0.3 per cent) occurred within ninety
      days after the 2736 procedures. Four deaths (mortality rate, 0.15 per cent)
      occurred during the initial hospitalization. The cause of seven of the deaths was
      determined. Three patients died as a result of preexisting disease (severe
      hepatorenal disease, metastatic esophageal cancer, or severe cardiac disease),
      and one patient died from sepsis with a gram-negative organism during a
      thoracotomy eight days postoperatively. A bleeding complication that occurred
      while the patient was receiving warfarin therapy led to the death of two other
      patients; one of these deaths occurred in 1974 and the other, in 1982. At the
      time that these patients were managed, the desired prothrombin time was
      considered to be twice the control value. The remaining patient, who had had a
      clip placed on the inferior vena cava after a pulmonary embolus occurred in 1970,
      died secondary to acute, severe thrombosis of this vessel after a total hip
      arthroplasty in 1971. The patient for whom the cause of death was not determined
      had had an artificial aortic valve and had been receiving chronic warfarin
      therapy. She died suddenly eighty-nine days postoperatively; no autopsy was
      performed. No patient died as the direct result of a known pulmonary embolus. No
      deaths related to venous thromboembolic disease or its prophylaxis or treatment
      occurred after 1982 (1458 operations). We attribute this, in part, to reduced
      levels of warfarin prophylaxis and improved management with warfarin. The ninety
      day postoperative mortality rate after 2736 procedures performed over nearly
      three decades was low (0.3 per cent). This span of time included the period
      before the introduction of many current improvements in perioperative care, such
      as routine intubation of patients under general anesthesia, continuous monitoring
      of the electrocardiogram intraoperatively, and blood-gas determinations. When the
      patients who died as a result of known, severe preexisting disease were excluded,
      the mortality rate was 0.18 per cent (five of 2733).

PMID- 9759814
TI  - Total hip arthroplasty after operative treatment of an acetabular fracture.
AB  - Sixty-six primary total hip arthroplasties were performed to treat post-traumatic
      osteoarthrosis that had developed following an acetabular fracture and subsequent
      open reduction and internal fixation. The mean age of the patients at the time of
      the total hip arthroplasty was fifty-two years (range, nineteen to eighty years).
      The arthroplasty was performed with cement in forty-four hips and without cement
      in twenty hips; in the remaining two hips, the acetabular component was inserted
      without cement and the femoral component was inserted with cement (a so-called
      hybrid procedure). Scarring from a previous procedure, retained hardware,
      heterotopic bone, and residual osseous deformity and deficiency made the
      procedure more complex than routine total hip arthroplasty in most patients.
      However, only one of the sixty-six procedures was associated with an operative
      complication. Three patients were lost to follow-up. The remaining sixty-three
      patients were followed for a mean of 9.6 years (range, two to twenty years). The
      mean duration of follow-up was 14.9 years for the acetabular components inserted
      with cement, 11.6 years for the femoral components inserted with cement, 4.6
      years for the femoral components inserted without cement, and 3.9 years for the
      acetabular components inserted without cement. The mean Harris hip score improved
      from 49 points preoperatively to 93 points at the latest follow-up evaluation for
      the forty-six patients who did not have a revision procedure after the index
      arthroplasty. Seventeen patients had a revision; sixteen revisions were performed
      because of aseptic loosening of one or both components (nine acetabular and
      eleven femoral components). Mechanical failure (radiographic loosening or
      revision due to aseptic loosening) occurred in twenty-five hips. As determined
      with use of the Kaplan-Meier method, the ten-year survival rate, with revision
      due to aseptic loosening as the end point, was 78 per cent (95 per cent
      confidence interval, 66 to 92 per cent) for the prosthesis as a whole (that is,
      no revision of either component), 87 per cent (95 per cent confidence interval,
      76 to 99 per cent) for the acetabular component, and 84 per cent (95 per cent
      confidence interval, 72 to 97 per cent) for the femoral component. An age of less
      than fifty years (p = 0.02), a weight of eighty kilograms or more (p = 0.047),
      and large residual combined segmental and cavitary deficiencies in the acetabular
      bone (p < 0.0001) were significant risk factors for revision because of aseptic
      loosening. At the ten-year follow-up, none of the twenty-two acetabular
      components that had been inserted without cement had been revised or demonstrated
      radiographic loosening. The ten-year rate of failure due to aseptic loosening was
      higher than that in many reported series of total hip arthroplasties performed
      for other indications; this was probably partly because of the young mean age of
      the patients, the high number of patients who had Charnley class-A involvement,
      and the predominantly male cohort.

PMID- 9759815
TI  - Treatment of infection with debridement and retention of the components following
      hip arthroplasty.
AB  - Forty-two patients (forty-two hips) who had an infection following a hip
      arthroplasty were managed with open debridement, retention of the prosthetic
      components, and antibiotic therapy. After a mean duration of follow-up of 6.3
      years (range, 0.14 to twenty-two years), only six patients (14 per cent) -- four
      of nineteen who had had an early postoperative infection and two of four who had
      had an acute hematogenous infection -- had been managed successfully. Of the
      remaining thirty-six patients, three (7 per cent of the entire group) were being
      managed with chronic suppression with oral administration of antibiotics and
      thirty-three (79 per cent of the entire group) had had a failure of treatment.
      All nineteen patients who had a late chronic infection were deemed to have had a
      failure of treatment. Debridement had been performed at a mean of six days
      (range, two to fourteen days) after the onset of symptoms in the patients who had
      been managed successfully and at a mean of twenty-three days (range, three to
      ninety-three days) in those for whom treatment had failed. Debridement with
      retention of the prosthesis is a potentially successful treatment for early
      postoperative infection or acute hematogenous infection, provided that it is
      performed in the first two weeks after the onset of symptoms and that the
      prosthesis previously had been functioning well. In our experience, this
      procedure has not been successful when it has been performed more than two weeks
      after the onset of symptoms. Retention of the prosthesis should not be attempted
      in patients who have a chronic infection at the site of a hip arthroplasty as
      this approach universally fails.

PMID- 9759816
TI  - Neuropathic arthropathy of the shoulder.
AB  - We retrospectively reviewed the records of six men (seven shoulders) with
      neuropathic arthropathy of the shoulder who were referred to our shoulder service
      during a twenty-eight-year period (from 1969 through 1997). The etiology of the
      neuropathic condition was syringomyelia in five patients (six shoulders) and
      chronic alcoholism in one patient. Five patients (six shoulders) were initially
      misdiagnosed, and seven operative procedures that were unrelated to the etiology
      of the neuropathic condition were performed in four of these patients.
      Radiographs revealed destruction of the shoulder joint and marked resorption of
      the humeral head in all patients. Magnetic resonance images revealed a syrinx of
      the central cord in all of the patients except for the one who had chronic
      alcoholism.

PMID- 9759817
TI  - The treatment of symptomatic os acromiale.
AB  - During a four-year period, fourteen individuals (fifteen shoulders) who had been
      seen at the shoulder service of our institution because of pain in the shoulder
      had a radiographic finding of an os acromiale. On clinical examination, the pain
      appeared to be due to an unstable os acromiale because the patients had point
      tenderness over the acromion and pain on forward elevation of the shoulder. The
      diagnosis of an os acromiale was confirmed on radiographs, magnetic resonance
      images, or a bone scan. Eight patients had an associated tear of the rotator
      cuff. The os acromiale was located in the pre-acromion in one shoulder, the meso
      acromion in eleven shoulders, and the meta-acromion in three shoulders. At the
      operation, the anterior aspect of the acromion was found to be unstable in all
      shoulders. Eleven patients (twelve shoulders) had open reduction of the os
      acromiale and insertion of an autogenous iliac-crest bone graft. Of those
      patients, four (five shoulders) had open reduction and internal fixation with a
      tension-band procedure with use of pins and wires. Only one of those shoulders
      had a solid osseous union, and the other four shoulders had a non-union that was
      due to a disruption of the fixation. The remaining seven patients (seven
      shoulders) had open reduction and internal fixation with use of cannulated screws
      and a tension-band construct; a solid osseous union was achieved in all but one
      of them. One patient had excision of the pre-acromion, which relieved the pain.
      Two patients who had had failed open reduction and internal fixation had excision
      of a grossly unstable os acromiale in the meso-acromion; both patients had pain
      and weakness after this procedure. Of the twelve shoulders that had open
      reduction and bone-grafting, seven had union of the os acromiale; the average
      time to radiographic and clinical union was nine weeks (range, seven to twenty
      weeks). We concluded that, although it is rare, symptomatic unstable os acromiale
      does occur and can be effectively treated with use of autogenous bone-grafting
      and internal fixation with a rigid tension-band construct and cannulated screws.

PMID- 9759818
TI  - The Coonrad-Morrey total elbow arthroplasty in patients who have rheumatoid
      arthritis. A ten to fifteen-year follow-up study.
AB  - Sixty-nine patients (seventy-eight elbows) who had rheumatoid arthritis were
      managed with a Coonrad-Morrey total elbow arthroplasty between 1981 and 1986. At
      the time of the present review, forty-one patients (forty-six elbows) were alive
      and had been followed for at least ten years after the procedure (Group 1). The
      remaining twenty-eight patients (thirty-two elbows) had died or had had a
      revision less than ten years after the procedure or had been followed for less
      than ten years (Group 2). The patients in Group 1 had a younger mean age at the
      time of the procedure, but all other preoperative parameters were similar for
      both groups. At the latest follow-up evaluation, 97 per cent of the elbows (forty
      five of the forty-six in Group 1 and thirty-one of the thirty-two in Group 2)
      were not painful or were only mildly painful. The mean arc of flexion-extension
      was 28 to 131 degrees; this represents an increase of 13 degrees (15 degrees in
      Group 1 and 7 degrees in Group 2) compared with the preoperative value. The mean
      arc of pronation was 68 degrees, and the mean arc of supination was 62 degrees;
      this represents an increase of 21 degrees. The results for seventy-four of the
      seventy-eight elbows (all forty-six in Group 1 and twenty-eight of the thirty-two
      in Group 2) were considered satisfactory by the patients. One patient thought
      that the status of the elbow was unchanged compared with preoperatively, and
      three thought that it was worse. Seventy-six of the seventy-eight elbows had long
      term radiographic evaluation; the two remaining elbows were excluded because a
      resection arthroplasty had been performed. There were two loose ulnar components;
      one was associated with an infection, and the other had been causing no symptoms
      at the time of the patient's death. In addition, both components were
      radiographically loose in an elbow that had had a revision without cement after a
      previous total elbow arthroplasty. Five bushings (7 per cent) were completely
      worn, and six (8 per cent) were partially worn. Complications occurred in eleven
      elbows (14 per cent) and were serious, necessitating reoperation, in ten (13 per
      cent). Delayed complications included three avulsions of the triceps, two deep
      infections, two ulnar fractures, and one fracture of an ulnar component. In
      addition, two elbows were revised because of aseptic loosening. No patient had
      persistent ulnar neuritis or serious skin complications. At the latest clinical
      follow-up evaluation, according to the Mayo elbow performance score, forty-three
      of the seventy-eight elbows had an excellent result; twenty-six, a good result;
      seven, a fair result; and two (both in Group 2), a poor result. The rate of
      survival of the prosthesis was 92.4 per cent, with 86 per cent good or excellent
      and 14 per cent fair or poor results.

PMID- 9759819
TI  - Anti-infective efficacy of antiseptic-coated intramedullary nails.
AB  - The coating of medical devices with antimicrobial agents has recently emerged as
      a potentially effective method for the prevention of device-related infections.
      We examined the anti-infective efficacy of intramedullary nails coated with an
      antiseptic combination of chlorhexidine and chloroxylenol in a rabbit model of
      device-related infection after fixation of an open tibial fracture. The rabbits
      were randomized to receive 2.8-by-100-millimeter stainless-steel tibial
      intramedullary nails that either were uncoated or were coated with antiseptic.
      After administration of anesthesia and preoperative antibiotic prophylaxis, a
      tibial fracture was created and then reduced with insertion of the intramedullary
      nail. A bacterial inoculum of 10(6) colony-forming units of Staphylococcus aureus
      was injected into the intramedullary canal, and the wound was sutured.
      Radiographs of the tibiae were made postoperatively, and the rabbits were
      monitored daily. They were killed at six weeks, or earlier if there was
      dehiscence of the wound, the fracture became grossly unstable, or the rabbit
      failed to thrive. The use of the antiseptic-coated nails was associated with a
      significantly lower rate of device-related osteomyelitis (two of twenty-two; 9
      per cent) than the use of the uncoated nails (thirteen of twenty-one; 62 per
      cent) (p = 0.0003). The radiographic and histopathological findings were
      generally similar in the two groups of rabbits. Antiseptic agents were not
      detected in serum. The results suggest that antiseptic-coated fracture-fixation
      devices provide significant local protection against Staphylococcus aureus, which
      is the most common cause of infections related to orthopaedic devices.

PMID- 9759820
TI  - Function of the vascular endothelium after hypothermic storage at four degrees
      Celsius in a canine tibial perfusion model. The role of adrenomedullin in
      reperfusion injury.
AB  - The function of the vascular endothelium after cold storage at 4 degrees Celsius
      for one, three, five, and seven days was investigated in a canine tibial
      perfusion model. Function was assessed in terms of changes in perfusion pressure,
      changes in the concentration of endothelin in the venous effluent from the
      perfused tibiae, adrenomedullin-induced vascular smooth-muscle relaxation, and
      norepinephrine-induced pressor responses in the presence of acetylcholine, N(G)
      monomethyl-L-arginine acetate (an inhibitor of nitric oxide synthesis), or
      indomethacin (an inhibitor of prostaglandin synthesis) in phase 1 of the study.
      In phase 2 of the study, the effect of the infusion of tetraethylammonium (a
      potassium-channel blocker that inhibits the activity of endothelium-derived
      hyperpolarized factor) was analyzed. The baseline perfusion pressures increased
      in a time-dependent manner (p < 0.05). In tibiae that had been stored for one or
      three days, the production of endothelin-1 was less than one picogram per
      milliliter, but it markedly increased to a mean (and standard error of the mean)
      of 8.7 +/- 3.2 and 10.8 +/- 4.3 picograms per milliliter in tibiae that had been
      stored for five and seven days, respectively (p < 0.05). Acetylcholine attenuated
      the norepinephrine-induced pressor response in all groups (storage at 4 degrees
      Celsius for one, three, five, or seven days) compared with the response in the
      control tibiae (p < 0.05). Perfusion of acetylcholine in the tibiae that had been
      stored for three days significantly attenuated the pressor response to
      norepinephrine compared with that in the tibiae that had been stored for five
      days (p < 0.05). In the presence of N(G)-monomethyl-L-arginine acetate, the
      norepinephrine-induced pressor response significantly increased only in the
      tibiae that had been stored for one day (p < 0.05). In the presence of
      indomethacin, the norepinephrine-induced pressor response significantly decreased
      in the tibiae that had been stored at 4 degrees Celsius for one, three, or five
      days (p < 0.05). Infusion of adrenomedullin relaxed vascular smooth muscle in the
      tibiae that had been stored for one, three, five, or seven days (p < 0.05). In
      phase 2 of the study, perfusion of tetraethylammonium in the presence of
      acetylcholine increased the norepinephrine-induced pressor response in the tibiae
      that had been stored at 4 degrees Celsius for seven days to a mean of 168 +/- 20
      per cent, whereas perfusion with acetylcholine alone attenuated the
      norepinephrine-induced pressor response to a mean of 54.6 +/- 3.7 per cent.

PMID- 9759821
TI  - Angiosarcoma of the hand associated with chronic exposure to polyvinyl chloride
      pipes and cement. A case report.

PMID- 9759822
TI  - Failure of a stainless-steel femoral head of a revision total hip arthroplasty
      performed after a fracture of a ceramic femoral head. A case report.

PMID- 9759823
TI  - The use of ultrasonography in the diagnosis of occult fracture of the radial
      neck. A case report.

PMID- 9759824
TI  - Mechanoreceptors in joint function.

PMID- 9759825
TI  - Current concepts review. Prophylactic use of antibiotics for procedures after
      total joint replacement.

PMID- 9759826
TI  - Peroneal nerve entrapment.

PMID- 9759827
TI  - The prospective, randomized, double-blind clinical trial in orthopaedic surgery.

PMID- 9759828
TI  - The effect of fibular malreduction on contact pressures in an ankle fracture
      malunion model.

PMID- 9759829
TI  - Posterior decompression and stabilization for spinal metastases. Analysis of
      sixty-seven consecutive patients.

PMID- 9759830
TI  - Allograft reconstruction of the acetabulum after resection of stage-IIB sarcoma.
      Intermediate-term results.

PMID- 9759831
TI  - Total hip arthroplasty with cement in patients less than twenty years old. Long
      term results.

PMID- 9759832
TI  - Wrong-site surgery.

PMID- 9759833
TI  - Transcutaneous immunization with cholera toxin protects mice against lethal
      mucosal toxin challenge.
AB  - We recently reported that application of cholera toxin (CT) to the skin results
      in transcutaneous immunization and induces a systemic Ab response to both CT and
      coadministered Ags. In this paper, we demonstrate antitoxin IgG and IgA Abs in
      sera, lung washes, and stool samples from immunized mice as well as a broad
      spectrum of IgG subclasses (IgG1, IgG2a, IgG2b, and IgG3) in the sera. Mice
      immunized with CT by the transcutaneous route exhibited significant protection
      from intranasal challenge with a lethal dose of CT. Thus, clinically relevant
      immunity against mucosal toxin challenge can be achieved via the transcutaneous
      route.

PMID- 9759834
TI  - Detection of a high frequency of virus-specific CD4+ T cells during acute
      infection with lymphocytic choriomeningitis virus.
AB  - Lymphocytic choriomeningitis virus (LCMV), like many viruses, induces a profound
      activation and expansion of CD8+ T cells. In contrast, CD4+ T cells do not
      increase in total number during the acute infection. We show here that mice
      infected with LCMV have a low but detectable frequency (<1/300) of CD4+ T cells,
      as detected by IL-2 production in limiting dilution assays, to each of two class
      II peptides during the peak of the acute LCMV response and into long-term memory.
      However, during the peak of the acute CD4+ T cell response, >20% of the CD4+ T
      cells secreted IFN-gamma after stimulation with PMA and ionomycin, and >10% of
      the CD4+ T cells secreted IFN-gamma after stimulation with the LCMV peptides.
      Thus, these new sensitive assays reveal a heretofore unappreciated, yet profound
      Ag-specific CD4+ T cell response during viral infections.

PMID- 9759835
TI  - Cytokines regulate expression and function of the HIV coreceptor CXCR4 on human
      mature dendritic cells.
AB  - HIV-infected dendritic cells (DC) efficiently transmit infection to CD4+ T cells
      during the process of T cell activation. To further understand interactions
      between DC and HIV, cytokine regulation of HIV coreceptors on cultured Langerhans
      cells (cLC, as prototypes of mature DC) was studied. Expression of cell surface
      CXCR4 on cLC was up-regulated by IL-4 and TGF-beta1 and inhibited by IFN-alpha,
      IFN-beta, and IFN-gamma, whereas cytokines did not appreciably regulate CCR5.
      Changes in cell surface CXCR4 expression on cLC correlated with T cell-tropic
      (X4)-HIV envelope-mediated syncytium formation and X4-HIV infection levels. A
      relative increase in the ratio of type 2/type 1 cytokine production, which can
      occur in HIV disease, may up-regulate CXCR4 expression on mature DC and promote
      infection by X4 viruses. Importantly, these findings suggest that cytokine
      dysregulation may be linked to the emergence of X4-HIV strains as HIV-infected
      individuals progress to AIDS.

PMID- 9759836
TI  - p38 MAPK is required for CD40-induced gene expression and proliferation in B
      lymphocytes.
AB  - We have investigated the activation of the p38 MAPK pathway in response to CD40
      engagement in multiple B cell lines and in human tonsillar B cells to define the
      role of p38 MAPK in proliferation, NF-kappaB activation and gene expression.
      Cross-linking CD40 rapidly stimulates both p38 MAPK and its downstream effector,
      MAPKAPK-2. Inhibition of p38 MAPK activity in vivo with the specific cell
      permeable inhibitor, SB203580, under conditions that completely prevented MAPKAPK
      2 activation, strongly perturbed CD40-induced tonsillar B cell proliferation
      while potentiating the B cell receptor (BCR)-driven proliferative response.
      SB203580 also significantly reduced expression of a reporter gene driven by a
      minimal promoter containing four NF-kappaB elements, indicating a requirement for
      the p38 MAPK pathway in CD40-induced NF-kappaB activation. However, CD40-mediated
      NF-kappaB binding was not affected by SB203580, suggesting that NF-kappaB may not
      be a direct target for the CD40-induced p38 MAPK pathway. In addition, SB203580
      selectively reduced CD40-induced CD54/ICAM-1 expression, whereas CD40-dependent
      expression of CD40 and CD95/Fas and four newly defined CD40-responsive genes
      cIAP2, TRAF1, TRAF4/CART and DR3 were unaffected. Our observations show that the
      p38 MAPK pathway is required for CD40-induced proliferation and that CD40 induces
      gene expression via both p38 MAPK-dependent and -independent pathways.

PMID- 9759837
TI  - Urocanic acid enhances IL-10 production in activated CD4+ T cells.
AB  - The immunosuppressive effects of UV radiation have been well documented. This
      suppression has been attributed to the action of the cis form of urocanic acid
      (UCA), a photoproduct of trans-UCA, a natural constituent of the skin. Here, we
      show that mouse spleen cells preincubated with cis-UCA have a diminished
      proliferative response to allogeneic cells in MLC and to stimulation with anti
      CD3 mAb. Cells preincubated with cis-UCA also had a decreased ability to serve as
      APC and to stimulate the proliferation of allogeneic lymphocytes in MLC.
      Simultaneously, the production of IL-2 and IFN-gamma by cells preincubated with
      cis-UCA was decreased. However, IL-10 gene expression and IL-10 protein secretion
      by spleen cells stimulated in the presence of cis-UCA were significantly
      enhanced. The principal cell population displaying the cis-UCA-induced elevated
      production of IL-10 was CD4+ T cells, which were shown to be a direct target of
      cis-UCA action. This was also supported by the observation that production of IL
      10 by stimulated splenic non-T cells or by macrophages was not altered by cis
      UCA. The enhanced production of IL-10 by activated CD4+ T cells may represent a
      novel pathway of UVB radiation-induced, cis-UCA-mediated immunosuppression. We
      suggest that the elevated production of IL-10 by activated CD4+ T cells may
      account for the suppressor T cell phenomena described in UV-irradiated
      recipients.

PMID- 9759838
TI  - Identification of a cytoplasmic region of CD20 required for its redistribution to
      a detergent-insoluble membrane compartment.
AB  - CD20 is a B lymphocyte integral membrane protein with signal-transducing
      properties. Abs directed toward extracellular CD20 epitopes activate nonreceptor
      tyrosine kinases and modulate cell cycle progression of B lymphocytes. Recently,
      we demonstrated that binding of CD20 Abs to B cells induces the rapid
      redistribution of up to 95% of CD20 molecules to low density, detergent-insoluble
      membrane microdomains and induces the appearance of an approximately 50-kDa
      tyrosine-phosphorylated protein in the same compartment. Active relocalization of
      CD20 may thus be critical to the initiation of signaling events by CD20. The CD20
      cDNA sequence predicts a nonglycosylated protein with four transmembrane-spanning
      regions and intracellular amino and carboxyl termini. Here we provide
      verification of the location of both the intracellular and extracellular regions
      of the CD20 molecule and identify a membrane-proximal sequence in the cytoplasmic
      carboxyl tail that is required for CD20 to redistribute to detergent-insoluble
      membrane microdomains.

PMID- 9759839
TI  - CD148: a receptor-type protein tyrosine phosphatase involved in the regulation of
      human T cell activation.
AB  - Following ligation of the TCR and costimulatory molecules such as CD28, T cells
      proliferate and secrete cytokines. Several other cell surface molecules have been
      identified that are capable of augmenting activation mediated via the TCR. These
      include CD2, CD27, CD40 ligand, and signaling lymphocytic activation molecule.
      Here, we have characterized the expression and function of CD148, a recently
      identified receptor-type protein tyrosine phosphatase. CD148 is expressed at low
      levels on resting T cells, but is up-regulated following in vitro activation.
      Cross-linking CD148 with immobilized anti-CD148 mAb induced vigorous
      proliferation of anti-CD3 mAb-activated, highly purified peripheral blood T cells
      in an IL-2-dependent, cyclosporin A-sensitive manner. This effect was greatest
      after 8 days of in vitro culture, suggesting that this molecule is involved in
      the latter stages of a T cell response. CD148-induced proliferation was
      significantly greater for CD8+ T cells than for CD4+ T cells. Thus, CD148 is a
      receptor-type protein tyrosine phosphatase involved in the activation of T
      lymphocytes.

PMID- 9759840
TI  - A role for NK cells as regulators of CD4+ T cells in a transfer model of colitis.
AB  - Previous studies have shown that the chronic inflammation observed in the colon
      of IL-10-deficient (IL-10(-/-)) mice is mediated by CD4+ Th1 T cells and is
      dependent on the presence of IFN-gamma for its initial development. As CD4+ T
      cells from IL-10(-/-) mice will cause colitis when transferred into recombinase
      activating gene (Rag)-deficient recipients, we considered the possibility that
      the recipients' NK cells could be an important source of IFN-gamma for the
      development of colitis. Therefore, the ability of IL-10(-/-) CD4+ T cells to
      cause colitis in Rag-deficient recipients that had been depleted of NK cells was
      tested. Contrary to our expectations, NK cell-depleted recipients of IL-10(-/-)
      CD4+ T cells developed accelerated disease compared with nondepleted recipients.
      Furthermore, CD4+ T cells from normal mice (IL-10(+/+)) also caused colitis in NK
      cell-depleted recipient mice, but not in nondepleted recipients. NK cells
      inhibited effector CD4+CD45RBhigh T cells, and subsequent experiments showed that
      this effect was dependent on perforin. Thus NK cells can play an important role
      in down-regulating Thl-mediated colitis by controlling the responses of effector
      T cells to gut bacteria.

PMID- 9759841
TI  - Chemical chaperones enhance superantigen and conventional antigen presentation by
      HLA-DM-deficient as well as HLA-DM-sufficient antigen-presenting cells and
      enhance IgG2a production in vivo.
AB  - Chemical chaperones, first defined in studies of mutant cystic fibrosis
      transmembrane conductance regulator proteins, are small molecules that act as
      stabilizers of proteins in their native state and have the ability in some cases
      to rescue protein-folding mutants within cells. HLA-DM is an MHC II-specific
      molecular chaperone that facilitates peptide loading onto MHC II proteins and
      also stabilizes empty MHC II molecules prior to their acquisition of antigenic
      peptides. APC that lack HLA-DM exhibit quantitative defects in protein Ag as well
      as superantigen presentation. Here we show that both the superantigen and protein
      presentation defect in MHC II-transfected, HLA-DM-deficient T2 cells can be
      partially overcome by treating the APC with the chemical chaperones glycerol,
      DMSO, or trimethylamine oxide. These chemical chaperones also enhance
      superantigen and conventional Ag presentation by wild-type APC. In vivo, glycerol
      was found to act as an adjuvant and resulted in enhanced IgG2a production to
      trinitrophenyl-keyhole limpet hemocyanin (TNP-KLH). In vitro, the enhancement of
      Ag presentation by chemical chaperones was found to take place at the level of
      the APC and took several hours to develop. Subcellular fractionation experiments
      show that HLA-DM enhances presentation of peptides by dense endosome fractions
      whereas chemical chaperones enhance presentation by light membrane fractions
      (early endosome or plasma membrane). The mechanism by which these chemical
      chaperones augment Ag presentation is not defined, but flow cytometric analysis
      suggests that the enhancement may be due to a subtle effect on the stability of
      several different proteins at the cell surface.

PMID- 9759842
TI  - Selective ability of mouse CD1 to present glycolipids: alpha-galactosylceramide
      specifically stimulates V alpha 14+ NK T lymphocytes.
AB  - Mouse CD1 (mCD1) glycoproteins are known to present peptides, while human CD1
      molecules present glycolipids. In mice, mCD1-autoreactive NK T cells play
      critical roles in various immune responses, through the secretion of high amounts
      of cytokines. This study was initiated to determine whether glycolipids are
      involved in the autorecognition of mCD1 by NK T cells. Alpha-galactosylceramide
      (alpha-GalCer) was the only glycolipid tested capable of eliciting an mCD1
      restricted response by splenic T cells. Moreover, splenic T cells derived from
      mCD1-deficient mice were not stimulated by alpha-GalCer, suggesting that the
      responsive T cells are selected by mCD1. Using cytoflow techniques, we confirmed
      that, in response to alpha-GalCer, IFN-gamma-secreting cells displayed an NK T
      cell phenotype. The predominance of IFN-gamma vs IL-4, however, is determined by
      the type of mCD1+ APC, suggesting the potential for APC regulation of cytokine
      production by NK T cells. Among a panel of 10 mCD1-autoreactive T cell
      hybridomas, only the ones that express the typical V alpha 14 J alpha 281 TCR
      rearrangement of NK T cells responded to alpha-GalCer. Fixation or treatment of
      mCD1+ APCs with an inhibitor of endosomal acidification and the use of mCD1
      mutants unable to traffic through endosome still allowed alpha-GalCer to
      stimulate NK T cells. Thus, endosomal trafficking and Ag processing are not
      required for glycolipid recognition. In summary, alpha-GalCer might be the
      autologous ligand, or a mimic of a glycolipid ligand, involved in the mCD1
      mediated stimulation of NK T cells.

PMID- 9759843
TI  - The tetraspan protein CD82 is a resident of MHC class II compartments where it
      associates with HLA-DR, -DM, and -DO molecules.
AB  - In specialized APCs, MHC class II molecules are synthesized in the endoplasmic
      reticulum and transported through the Golgi apparatus to organelles of the
      endocytic pathway collectively called MHC class II compartments (MIICs). There,
      the class II-associated invariant chain is degraded, and peptides derived from
      internalized Ag bind to empty class II in a reaction that is facilitated by the
      class II-like molecule HLA-DM. An mAb raised to highly purified, immunoisolated
      MIICs from human B lymphoblastoid cells recognized CD82, a member of the
      tetraspan family of integral membrane proteins. Subcellular fractionation,
      immunofluorescence microscopy, and immunoelectron microscopy showed that CD82 is
      highly enriched in MIICs, particularly in their internal membranes.
      Coprecipitation analysis showed that CD82 associates in MIICs with class II, DM,
      and HLA-DO (an inhibitor of peptide loading that binds DM). Similar experiments
      showed CD63, another tetraspan protein found in MIICs, also associates with these
      molecules in the compartment and that CD82 and CD63 associate with each other.
      Preclearing experiments demonstrated that both CD82 and CD63 form complexes with
      DM-associated class II and DM-associated DO. The ability of CD82 and CD63 to form
      complexes with class II, DM, and DO in MIICs suggests that the tetraspan proteins
      may play an important role in the late stages of MHC class II maturation.

PMID- 9759844
TI  - Superantigen-driven, CD8+ T cell-mediated down-regulation: CD95 (Fas)-dependent
      down-regulation of human Ig responses despite CD95-independent killing of
      activated B cells.
AB  - Staphylococcal superantigens, including staphylococcal enterotoxin B (SEB),
      promote vigorous T cell-dependent Ig responses at low dose (0.01 ng/ml). In
      contrast, more mitogenic high dose SEB (100 ng/ml) profoundly inhibits the Ig
      responses. To assess the contribution of CD8+ T cells to this inhibition, high
      dose SEB-dependent killing of activated B cells and down-regulation of Ig
      responses were determined. Rapid killing (4 h) of activated B cells was effected
      by high dose SEB-activated CD8+ T cells (CD8*), but not by high-dose SEB
      activated CD4+ T cells (CD4*), and required the presence of high dose SEB during
      the cytotoxicity assay. This killing was abrogated by chelation of extracellular
      calcium or by treatment with concanamycin A but was only modestly affected by
      treatment with brefeldin A, suggesting a perforin-based pathway of killing.
      Despite their widely disparate abilities to rapidly kill activated B cells, CD8*
      and CD4* demonstrated similar quantitative abilities to effect high dose SEB
      dependent down-regulation of Ig responses. Antagonist anti-CD95 mAb substantially
      reversed high dose SEB-dependent downregulation effected by CD8* but had no
      appreciable effects on high dose SEB-dependent killing of activated B cells.
      These observations strongly suggest that the small fraction of activated B cells
      that secrete Ig are selectively sensitive to CD95-based killing but resistant to
      CD95-independent killing. This finding may help explain why clinical autoimmunity
      associated with increased titers of autoantibodies is a predominant feature of
      defects in CD95 or CD95 ligand.

PMID- 9759845
TI  - IL-10 is critical in the regulation of autoimmune encephalomyelitis as
      demonstrated by studies of IL-10- and IL-4-deficient and transgenic mice.
AB  - Experimental autoimmune encephalomyelitis (EAE) and other organ-specific
      autoimmune diseases are induced by autoantigen-specific Th1 cells. In contrast,
      transfer of autoantigen-reactive Th2 cells that produce IL-4 and IL-10 can
      prevent and/or reverse EAE. The relative roles of these two Th2 cytokines in the
      regulation of EAE has not been evaluated. Utilizing IL-4 and IL-10 knockout mice
      deficient for these cytokines and IL-10 and IL-4 transgenic mice overexpressing
      these cytokines, we demonstrate that IL-10-deficient mice (IL-10(-/-)) are more
      susceptible and develop a more severe EAE when compared with IL-4-deficient mice
      (IL-4(-/-)) or wild-type mice. T cells from IL-10(-/-) mice exhibit a stronger Ag
      specific proliferation, produce more proinflammatory cytokines (IFN-gamma and TNF
      alpha) when stimulated with an encephalitogenic peptide, and induce very severe
      EAE upon transfer into wild-type mice. In contrast, while IL-4 transgenic mice
      develop similar disease compared with their nontransgenic littermates, mice
      transgenic for IL-10 are completely resistant to the development of EAE. Taken
      together, our data suggest that IL-10 plays a more critical role in the
      regulation of EAE by regulating autopathogenic Th1 responses.

PMID- 9759846
TI  - Expansion by self antigen is necessary for the induction of experimental
      autoimmune encephalomyelitis by T cells primed with a cross-reactive
      environmental antigen.
AB  - Cross-reactivity with environmental antigens has been postulated as a mechanism
      responsible for the induction of autoimmune disease. Experimental autoimmune
      encephalomyelitis is a T cell-mediated autoimmune disease model inducible in
      susceptible strains of laboratory animals by immunization with protein
      constituents of myelin. We used myelin proteolipid protein (PLP) peptide 139-151
      and its analogues to define motifs to search a protein database for structural
      homologues of PLP139-151 and identified five peptides derived from microbial Ags
      that elicit immune responses that cross-react with this self peptide. Exposure of
      naive SJL mice to the cross-reactive environmental peptides alone was
      insufficient to induce autoimmune disease even when animals were treated with Ag
      nonspecific stimuli (superantigen or LPS). However, immunization of SJL mice with
      suboptimal doses of PLP139-151 after priming with cross-reactive environmental
      peptides consistently induced experimental autoimmune encephalomyelitis.
      Furthermore, T cell lines from mice immunized with cross-reactive environmental
      peptides and restimulated in vitro with PLP139-151 could induce disease upon
      transfer into naive recipients. These data suggest that expansion by self Ag is
      required to break the threshold to autoimmune disease in animals primed with
      cross-reactive peptides.

PMID- 9759847
TI  - Neonatal murine B lymphocytes respond to polysaccharide antigens in the presence
      of IL-1 and IL-6.
AB  - Unlike adults, neonates are unable to respond to polysaccharide Ags, making them
      especially vulnerable to pathogenic encapsulated bacteria. Since the Ab response
      to polysaccharides in adult mice requires certain cytokines, it was hypothesized
      that neonatal murine B cells may be competent to respond to such Ags, but may
      fail to do so due to a deficiency of cytokines. Neonatal splenocyte cultures,
      which were otherwise unresponsive to trinitrophenyl (TNP)-Ficoll, a haptenated
      polysaccharide Ag, mounted an adult-like Ab response when supplemented with IL-1.
      However, IL-1 failed to induce such a response to TNP-Ficoll when purified B
      cells were used instead. Although IL-6 alone did not induce a response in whole
      spleen cells or purified B cells from neonates, it synergized with IL-1 in
      inducing purified neonatal B cells to respond to TNP-Ficoll. The avidity of the
      cytokine-induced neonatal anti-TNP Abs was comparable to that of Abs made by
      adult splenocyte cultures. One effect of IL-1 may be at the level of clonal
      expansion, since it induced neonatal B cells to proliferate in response to anti
      IgM, which was further enhanced by IL-6. The spontaneous secretion of IL-1 by
      neonatal splenocytes was below the detection limit, while adult splenocytes
      secreted 30.8 +/- 5.2 U/ml, which is of the same order of magnitude as what was
      required to stimulate neonatal B cells to respond to TNP-Ficoll. Thus, the
      neonatal unresponsiveness to polysaccharide Ags could be due to the inability of
      a non-B cell population resident in the neonatal spleen to secrete sufficient
      quantities of IL-1.

PMID- 9759848
TI  - CD16 cross-linking blocks rearrangement of the TCR beta locus and development of
      alpha beta T cells and induces development of NK cells from thymic progenitors.
AB  - Mouse thymocytes normally develop into T lymphocytes, but the embryonic thymus
      also contains precursor cells capable of developing into NK cells. Here, we
      describe conditions that induce pro-T cells to develop into NK cells. CD16 is
      expressed on thymic pro-T cells. We observed that CD16 cross-linking during
      culture of embryonic thymic organs suppressed rearrangement of the TCR beta locus
      (but did not inhibit TCR gamma locus rearrangement). Rearrangement of the TCR
      beta locus is normally required for development to the CD4+CD8+, and this
      development was also suppressed by CD16 cross-linking. The ability of CD16 cross
      linking to block alpha beta T cell development was not attributable to toxic
      effects, but rather was accompanied by promotion of development into NK cells,
      identified based on molecular and functional criteria. These results suggest that
      common lymphoid precursors can respond to environmental signals to commit to the
      alpha beta T vs NK developmental pathways.

PMID- 9759849
TI  - Roles of chemokines and receptor polarization in NK-target cell interactions.
AB  - We report that the ability of NK cells to produce chemokines is increased in NK
      target cell conjugates. The chemokines produced play a critical role in the
      polarization and recruitment of NK cells as well as in the NK effector-target
      cell conjugate formation. Chemokines induce the formation of two specialized
      regions in the NK cell: the advancing front or leading edge, where chemokine
      receptors CCR2 and CCR5 cluster, which might guide the cells toward the
      chemotactic source, and the uropod, where adhesion molecules ICAM-1 and -3 are
      redistributed. NK cell polarity was intrinsically involved in conjugate
      formation. The redistribution of both adhesion receptors and CCR was preserved
      during the formation of NK-target cell conjugates. Time-lapse videomicroscopy
      studies of the formation of effector-target conjugates showed that morphologic
      poles are also functionally distinct; while the binding to target cells was
      preferentially mediated through the leading edge, the uropod was found at the
      rear of migrating NK cells and recruited additional NK cells to the vicinity of
      K562 target cells. Inhibition of cell polarization and adhesion receptor
      redistribution blocked the formation of NK-K562 cell conjugates and the cytotoxic
      activity of NK cells. We discuss the implication of NK-cell polarization in the
      development of cytotoxic responses.

PMID- 9759851
TI  - Expression and function of CTLA-4 in Th1 and Th2 cells.
AB  - CTLA-4 is expressed on T cells after activation and shares homology with the CD28
      costimulatory receptor. In contrast to CD28, CTLA-4 is thought to be a negative
      regulator of T cell activation. Cross-linking of CTLA-4 during activation of
      peripheral T cells reduces IL-2 production and arrests T cells in G1. Much less
      is known about the function of CTLA-4 in differentiated T cells. We have
      investigated the expression and function of CTLA-4 in established Th1 and Th2
      clones and in bulk populations of Th1 and Th2 cells freshly derived in vitro from
      TCR transgenic splenocytes. We found that CTLA-4 was induced under similar
      conditions and with similar kinetics following activation of both Th1 and Th2
      clones. However, CTLA-4 expression was much higher in Th2 than Th1 clones and
      lines. This was confirmed by flow cytometry, confocal microscopy, and Northern
      blot analysis. The ratio of surface to intracellular expression of CTLA-4 and its
      rate of endocytosis were similar in Th1 and Th2 clones. Inhibition of binding of
      CTLA-4 to its ligands using soluble anti-CTLA-4 mAb during stimulation with Ag
      increased the production not only of IL-2 by Th1 clones, but also that of IL-3
      and IFN-gamma by Th1 clones and of IL-3, IL-4, IL-5, and IL-10 by Th2 clones. In
      contrast, when anti-CTLA-4 was coimmobilized with anti-CD3 and anti-CD28 mAbs, a
      decrease in the production of multiple cytokines was observed. We conclude that
      CTLA-4 can function to suppress the production of cytokines produced by both Th1
      and Th2 cells.

PMID- 9759850
TI  - Generation of biologically active IL-1 beta by matrix metalloproteinases: a novel
      caspase-1-independent pathway of IL-1 beta processing.
AB  - Biologic activity of IL-1 beta requires processing of the inactive precursor, a
      function generally ascribed to IL-1 beta-converting enzyme (caspase-1). However,
      alternative mechanisms of IL-1 beta activation have been postulated in local
      inflammatory reactions. Expression of IL-1 beta and matrix metalloproteinases
      (MMPs) frequently occurs simultaneously at sites of inflammation. We describe
      here that stromelysin-1 (MMP-3), as well as the gelatinases A (MMP-2) and B (MMP
      9), processes recombinant human IL-1 beta precursor (pIL-1 beta) into
      biologically active forms. Detection of both pIL-1 beta processing and biologic
      IL-1 beta activity demonstrated different processing capacities of the respective
      MMPs. Conversion of pIL-1 beta by stromelysin-1 required coincubation for at
      least 1 h, and biologic activity faded after 8 h to 24 h. Gelatinase A was less
      effective in processing pIL-1 beta, requiring at least 24 h of coincubation. In
      contrast, gelatinase B processed pIL-1 beta within minutes, resulting in
      immunoreactive products as well as biologic activity stable for 72 h. In
      addition, prolonged incubation of mature IL-1 beta with stromelysin-1, and to a
      lesser extent also with gelatinases, but not with interstitial collagenase,
      resulted in the degradation of mature IL-1 beta. None of the MMPs processed the
      second isoform of IL-1, IL-1 alpha. The present study indicates a biphasic
      regulation of IL-1 beta activity by MMPs: a caspase-1-independent pathway of IL-1
      beta activation and inhibition of IL-1 beta activity by degrading the mature
      cytokine. The balance of the respective MMPs and pIL-1 beta might regulate the
      long term appearance of IL-1 beta activity at sites of acute or chronic
      inflammation.

PMID- 9759852
TI  - Fine specificity of the myelin-reactive T cell repertoire: implications for TCR
      antagonism in autoimmunity.
AB  - The use of altered peptide ligands (APL) to modulate T cell responses has been
      suggested as a means of treating T cell-mediated autoimmune disorders. We have
      assessed the therapeutic potential of TCR antagonist peptides in autoimmunity
      using murine experimental autoimmune encephalomyelitis (EAE) as a model. The Tg4
      transgenic mouse expresses an MHC class II-restricted TCR specific for the
      immunodominant encephalitogenic epitope of myelin basic protein, Ac1-9
      (acetylated N-terminal nonamer). We have used T cell lines derived from Tg4 mice
      to define the TCR contact residues within Ac1-9. APL with appropriate
      substitutions at the primary TCR contact residue were effective antagonists of
      Tg4 T cells. These antagonist APL, however, were found to induce EAE in
      susceptible, nontransgenic strains of mice. Underlying this, the Ac1-9-specific T
      cell repertoire of normal mice, rather than reflecting the Tg4 phenotype, showed
      considerable diversity in fine specificity and was able to respond to the Tg4
      antagonist APL. Defining antagonist APL in vitro using T cell clones, therefore,
      was not a reliable approach for the identification of APL with EAE-suppressing
      potential in vivo. Our findings highlight the complexities of the autoreactive T
      cell repertoire and have major implications for the use of APL in autoimmune
      diseases.

PMID- 9759853
TI  - Steroid hormone regulation of cytokine secretion by proteolipid protein-specific
      CD4+ T cell clones isolated from multiple sclerosis patients and normal control
      subjects.
AB  - Steroid hormones have long been known to modulate immune function, and recent
      studies indicate that one of the means by which they do so involves effects on
      the secretion of immunoregulatory cytokines. Our laboratory has found recently
      that estradiol (E2) selectively modifies cytokine secretion in proteolipid
      protein (PLP)-specific, CD4+ T cell clones isolated from patients with the
      demyelinating disease, multiple sclerosis, and from normal control subjects. The
      data suggest that E2 may play a role in regulating the balance between pro- and
      antiinflammatory conditions, especially at concentrations typical of pregnancy.
      To determine whether other pregnancy-associated steroid hormones are capable of
      similar activity, we expanded our testing to include estrone (E1), estriol (E3),
      progesterone, and dexamethasone. The results indicate that E1 and E3 enhance
      secretion of Ag- or anti-CD3-stimulated IL-10 and IFN-gamma in dose-dependent
      fashion, almost identical to that of E2. The effect on IL-10 was more potent than
      occurred with IFN-gamma. In addition, E1 and E3, like E2, had a biphasic effect
      on TNF-alphabeta secretion, with low concentrations stimulatory, and high doses
      inhibitory. None of the estrogens influenced IL-4 or TGF-beta secretion.
      Progesterone enhanced secretion of IL-4, without affecting any other tested
      cytokine. Finally, dexamethasone induced TGF-beta secretion, but inhibited IFN
      gamma and TNF-alphabeta. This differential effect of steroid hormones on the
      secretion of cytokines by CD4+ human T cell clones is consistent with the
      possibility that, collectively, they promote antiinflammatory conditions at high
      concentrations typical of pregnancy.

PMID- 9759854
TI  - Caspase-independent cell death induced by anti-CD2 or staurosporine in activated
      human peripheral T lymphocytes.
AB  - We examined the effects of the cell-permeable, broad spectrum peptide caspase
      inhibitors, benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethyl ketone (Z-VAD.fmk),
      and BOC-Asp(OMe)-fluoromethyl ketone (BOC-D.fmk), on apoptosis induced by anti
      CD2, anti-Fas, and the protein kinase inhibitor staurosporine in activated human
      peripheral T lymphocytes. We monitored ultrastructural, flow cytometric, and
      biochemical apoptotic changes, including externalization of phosphatidylserine,
      cleavage of poly(ADP-ribose) polymerase (PARP) and lamins, activation of caspase
      3 and caspase-7, decrease in mitochondrial membrane potential, and DNA
      fragmentation. Z-VAD.fmk and BOC-D.fmk completely inhibited all the biochemical
      and ultrastructural changes of apoptosis in anti-Fas-treated cells. In marked
      contrast, neither Z-VAD.fmk nor BOC-D.fmk inhibited CD2- or staurosporine
      mediated cell shrinkage, dilatation of the endoplasmic reticulum (seen in anti
      CD2-treated cells), externalization of phosphatidylserine, and loss of
      mitochondrial membrane potential that accompanied cell death. However, these
      inhibitors did inhibit the cleavage of PARP and lamins and the formation of
      hypodiploid cells, and partially inhibited chromatin condensation. These results
      demonstrate that in activated T cells, anti-CD2 and staurosporine induce a
      caspase-independent cell death pathway that exhibits prominent cytoplasmic
      features of apoptosis. However, caspase activation is required for the
      proteolytic degradation of nuclear substrates such as PARP and lamins together
      with the DNA fragmentation and extreme chromatin condensation that occur in
      apoptotic cells.

PMID- 9759855
TI  - Epidermal growth factor (EGF) modulates fetal thymocyte growth and
      differentiation: partial reversal by insulin, mimicking by specific inhibitors of
      EGF receptor tyrosine kinase activity, and differential expression of CD45
      phosphatase isotypes.
AB  - We have recently reported that epidermal growth factor (EGF) modulates thymocyte
      development in fetal thymus organ cultures. Exogenously added EGF arrested
      thymocyte growth and differentiation, acting at the transition from the CD4-CD8-
      (double-negative (DN)) to the CD4+CD8+ (double-positive (DP)) phenotype. In this
      study, we further investigate some molecular aspects of this blockade. This
      inhibitory effect could be mimicked by tyrphostins, which are selective
      inhibitors of EGF receptor kinase activity. An attempt to use insulin (INS) as a
      synergizing effector resulted in partial restoration of lobe cellularity, leading
      to expansion of the CD44-CD25+ DN subset. However, INS did not overcome the EGF
      driven blockade of the thymocyte DN --> DP transition. Analysis of CD45
      phosphatase showed that this transition was preceded by a rise in CD45RB isotype
      expression. At the end of a 7-day culture, the remaining DN cells from both EGF-
      and EGF+INS-treated fetal thymus organ cultures showed a CD45RB- phenotype and
      were negative for the EGF-immunoreactive molecule described previously on the
      fetal thymocyte surface. This finding implies that neither molecule is related to
      the growth capability of cells at this early developmental stage; it is more
      likely that the molecules are related to subsequent events in the thymocyte
      pathway to the DP phenotype. Thus, our data support the concept that EGF receptor
      related circuitry may be relevant in thymus ontogeny. Additionally, evidence is
      provided for the duality between growth and differentiation at this particular
      early stage of thymocyte development.

PMID- 9759856
TI  - Gamma 3 gene-disrupted mice selectively deficient in the dominant IgG subclass
      made to bacterial polysaccharides undergo normal isotype switching after
      immunization with polysaccharide-protein conjugate vaccines.
AB  - Bacterial polysaccharides (PS) are T-independent type 2 Ags that elicit
      restricted Ab responses of IgM and IgG3 in mice and IgM and predominantly IgG2 in
      humans. Immunodeficiency in the dominant IgG subclass made to PS is associated
      with chronic sinus and pulmonary infections with PS-encapsulated bacteria. To
      elucidate the biologic role of the dominant IgG subclass in the immune response
      to PS and to make an animal model of human IgG subclass deficiency, we generated
      mice with a targeted disruption of the exon encoding the CH1 domain of the gamma
      3 heavy-chain constant region gene. Homozygotes had no detectable serum IgG3, and
      their splenocytes did not produce IgG3 after LPS stimulation. IgG3(-/-) mice
      immunized with PS from Pseudomonas aeruginosa LPS O-side chain or Streptococcus
      pneumoniae type 19F capsule did not produce any IgG3 anti-PS Abs, in contrast to
      wild-type mice in which IgG3 was the major IgG subclass. Immunizing both wild
      type and IgG3(-/-) mice with 19F PS-protein conjugate elicited IgG1 Abs. We
      conclude that IgG3(-/-) mice have a selective deficiency in the dominant murine
      IgG subclass made to T-independent type 2 Ags and may be a useful animal model of
      IgG subclass deficiency. In addition, we show that the anti-PS Ab class switching
      to IgG1 that occurs when mice are immunized with a PS-protein conjugate vaccine
      does not require sequential Ig expression or an intact, upstream gamma 3 heavy
      chain gene.

PMID- 9759857
TI  - IL-12 up-regulates IL-18 receptor expression on T cells, Th1 cells, and B cells:
      synergism with IL-18 for IFN-gamma production.
AB  - IL-18 is a product of macrophages and with IL-12 strikingly induces IFN-gamma
      production from T, B, and NK cells. Furthermore, IL-18 and 1L-12 synergize for
      IFN-gamma production from Th1 cells, although this combination fails to affect
      Th2 cells. In this study, we show that IL-12 and IL-18 promptly and
      synergistically induce T and B cells to develop into IFN-gamma-producing cells
      without engaging their Ag receptors. We also studied the mechanism underlying
      differences in IL-18 responsiveness between Th1 and Th2 cells. Pretreatment of T
      or B cells with IL-12 rendered them responsive to IL-18, which induces cell
      proliferation and IFN-gamma production. These IL-12-stimulated cells had both
      high and low affinity IL-18R and an increased IL-18R mRNA expression. In
      particular, IL-12-stimulated T cells strongly and continuously expressed IL-18R
      mRNA. However, when T cells developed into Th1 cells after stimulation with anti
      CD3 and IL-12, they lowered this IL-12-induced-IL-18R mRNA expression. Then, such
      T cells showed a dominant response to anti-CD3 by IFN-gamma production when they
      were subsequently stimulated with anti-CD3 and IL-18. In contrast, Th2 cells did
      not express IL-18R mRNA and failed to produce IFN-gamma in response to anti-CD3
      and IL-18, although they produced a substantial amount of IFN-gamma in response
      to anti-CD3 and IL-12. However, when Th1 and Th2 cells were stimulated with anti
      CD3, IL-12, and IL-18, only the Th1 cells markedly augmented IFN-gamma production
      in response to IL-18, suggesting that IL-18 responsiveness between Th1 and Th2
      cells resulted from their differential expression of IL-18R.

PMID- 9759858
TI  - IL-15 promotes IL-12 production by human monocytes via T cell-dependent contact
      and may contribute to IL-12-mediated IFN-gamma secretion by CD4+ T cells in the
      absence of TCR ligation.
AB  - At inflammatory sites, the number of activated bystander T cells exceeds that of
      Ag-activated T cells. We investigated whether IL-15, a monocyte-derived cytokine
      that shares several biologic activities with IL-2, may contribute to bystander T
      cell activation in the absence of IL-2 and triggering Ag. The addition of IL-15
      to cocultures of monocytes and T cells stimulates CD4+ but not CD8+ T cells to
      produce IFN-gamma. IFN-gamma production requires endogenous IL-12, the production
      of which in turn is dependent upon CD40/CD154 interactions between CD4+ T cells
      and monocytes. Indeed, non-TCR-activated CD4+ but not CD8+ T cells express
      significant levels of CD154. IL-15 may enhance IFN-gamma in this system by up
      regulating CD40 expression on monocytes and IL-12Rbeta1 expression on CD4+ T
      cells. Conversely, using neutralizing anti-IL-15 mAb, we show that the ability of
      IL-12 to augment IFN-gamma secretion is partly mediated by endogenous IL-15.
      Finally, in the absence of monocytes, a synergistic effect between exogenous IL
      12 and IL-15 is necessary to induce IFN-gamma production by purified CD4+ T
      cells, while IL-15 alone induces T cell proliferation. It is proposed that this
      codependence between IL-12 and IL-15 for the activation of inflammatory T cells
      may be involved in chronic inflammatory disorders that are dominated by a Th1
      response. In such a response, a self-perpetuating cycle of inflammation is set
      forth, because IL-15-stimulated CD4+ T cells may activate monocytes to release IL
      12 that synergizes with IL-15 to induce IL-12 response and IFN-gamma production.

PMID- 9759859
TI  - Impaired TCR-mediated apoptosis and Bcl-XL expression in T cells lacking the
      stress kinase activator SEK1/MKK4.
AB  - The dual specificity kinase SEK1 (MKK4) is a direct activator of stress-activated
      protein kinases (SAPK/JNK) in response to environmental stresses or mitogenic
      factors. We show in Sek1(-/-)Rag(-/-) chimeric mice that a Sek1 null mutation
      augments the susceptibility of peripheral T cells to TCR/CD3 religation-induced
      apoptosis. Sek1(-/-) T cells failed to induce expression of the death suppressor
      Bcl-XL in response to Ag receptor activation. The Sek1 mutation did not alter the
      induction of apoptosis in response to etoposide, cisplatinum, Adriamycin, and
      gamma-irradiation. Moreover, we show that CD3epsilon activation alone leads to
      SEK1 activation in Sek1(+/+) T cells. These results suggest that SEK1 transduces
      cellular survival signals during T cell stimulation.

PMID- 9759860
TI  - Selective inhibitors of cytosolic or secretory phospholipase A2 block TNF-induced
      activation of transcription factor nuclear factor-kappa B and expression of ICAM
      1.
AB  - TNF signaling mechanisms involved in activation of transcription factor NF-kappaB
      were studied in the human keratinocyte cell line HaCaT. We show that TNF-induced
      activation of NF-kappaB was inhibited by the well-known selective inhibitors of
      cytosolic phospholipase A2 (cPLA2): the trifluoromethyl ketone analogue of
      arachidonic acid (AACOCF3) and methyl arachidonyl fluorophosphate. The
      trifluoromethyl ketone analogue of eicosapentaenoic acid (EPACOCF3) also
      suppressed TNF-induced NF-kappaB activation and inhibited in vitro cPLA2 enzyme
      activity with a similar potency as AACOCF3. The arachidonyl methyl ketone
      analogue (AACOCH3) and the eicosapentanoyl analogue (EPACHOHCF3), which both
      failed to inhibit cPLA2 enzyme activity in vitro, had no effect on TNF-induced NF
      kappaB activation. TNF-induced NF-kappaB activation was also strongly reduced in
      cells stimulated in the presence of the secretory PLA2 (sPLA2) inhibitors 12-epi
      scalaradial and LY311727. Addition of excess arachidonic acid suppressed the
      inhibitory effect of 12-epi-scalaradial and LY311727. Moreover, both methyl
      arachidonyl fluorophosphate and 12-epi-scalaradial blocked TNF-mediated
      enhancement of expression of ICAM-1. Activation of NF-kappaB by IL-1beta was
      markedly less sensitive to both cPLA2 and sPLA2 inhibitors. The results indicate
      that both cPLA2 and sPLA2 may be involved in the TNF signal transduction pathway
      leading to nuclear translocation of NF-kappaB and to NF-kappaB-activated gene
      expression in HaCaT cells.

PMID- 9759861
TI  - Mechanisms of hyaluronan-induced up-regulation of ICAM-1 and VCAM-1 expression by
      murine kidney tubular epithelial cells: hyaluronan triggers cell adhesion
      molecule expression through a mechanism involving activation of nuclear factor
      kappa B and activating protein-1.
AB  - The matrix constituent hyaluronan (HA) markedly accumulates in inflammatory
      lesions. To gain insight into the biologic significance of this phenomenon we
      tested the hypothesis that HA could regulate cell adhesion molecule expression in
      epithelial cells. Using a clonal line of mouse cortical tubular (MCT) cells we
      found that fragmented intermediate m.w., but not high m.w., HA markedly increased
      ICAM-1 and VCAM-1 steady state mRNA and cell surface expression. Up-regulation of
      ICAM-1 and VCAM-1 mRNA by HA was preceded by a marked increase in NF-kappaB and
      activating protein-1 DNA binding activity in MCT cells. Transcript levels for the
      NF-kappaB inhibitor IkappaBalpha and for the activating protein-1 constituents c
      jun and c-fos also increased in response to HA stimulation of tubular cells.
      Inhibition of NF-kappaB with the serine protease inhibitor N-tosyl-L
      phenylalanine chloromethyl ketone blocked the HA-mediated expression of ICAM-1
      and VCAM-1 in MCT cells. In conclusion, HA displays proinflammatory effects by
      directly stimulating the expression of the cell adhesion molecules ICAM-1 and
      VCAM-1 in mouse kidney epithelial cells. HA could thereby play an important role
      in leukocyte adhesion in inflammatory renal diseases.

PMID- 9759862
TI  - C4d DNA sequences of two infrequent human allotypes (C4A13 and C4B12) and the
      presence of signal sequences enhancing recombination.
AB  - The DNA sequences of the polymorphic region (C4d) that belong to the infrequent
      complement C4 allotypes C4A13 and C4B12 have been obtained. In addition, C4A4 and
      C4B2 C4d sequences have been completed. C4A13 shows a new combination of amino
      acids at the following polymorphic positions: Asp1054, Pro1101 Cys1102, Leu1105,
      Asp1106, Asn1157, Ala1188, and Arg1191. These amino acids conform to the
      antigenic determinants Chido 1 and Rodgers 3; thus C4A13 is the only allele
      described thus far that carries both Ags. C4A13 and C4A4 carry the motif "ggctc*"
      (* means "deletion") at positions 14 to 19 in their intron 28; this motif had
      previously been reported only in C4B alleles. The C4B12 nucleotide sequence is
      analogous to C4B1b and C4B3 sequences, except for codon 1076, which is GCC in
      C4B1b and C4B3 and GGA in C4B12, which is coding for glycine in both cases. A
      recombination model for the generation of C4 alleles is formulated based on the
      analysis of these new sequences. One recombination would take place between
      positions 1157 and 1186 and would give rise to C4A13 and C4B5 or C4A3 (or C4A6)
      and C4B2; another one would occur between positions 1054 and 1076 and would
      generate C4A3 (or C4A6) and C4B12 or C4A2 and C4Bnew. Analysis of 1157 to 1186
      and 1054 to 1076 fragments reveals the presence of putative sequence signals for
      recombination (similar to Escherichia coli chi recombination signal); the
      accumulation of such signals in fragments 1054 to 1076 supports the notion that a
      recombination hot spot for the C4 gene may exist and it also enhances new allele
      generation and intraspecies C4 gene homogenization.

PMID- 9759863
TI  - Differential usage of VH gene segments is mediated by cis elements.
AB  - Ig diversity is generated in large part by the combinatorial joining of the Ig
      gene segments, VH, D, and JH, that together encode the variable domain of Ig. The
      final Ig repertoire, however, not only reflects the diversity generated through
      V(D)J recombinatorial joining, but it is also the product of a number of
      developmental restraints and selections. To avoid such restrictions and assess
      the recombination potential of individual Ig gene segments, we constructed Ig
      heavy (H) chain microlocus plasmids, each of which contain germline coding,
      recombination signal, and flanking sequences of a VH, D, and JH gene segment.
      These plasmids allow us to assess the recombination potential of the segments in
      the context of their natural flanking DNA sequences, but in the absence of any
      higher order chromatin structure or cellular selection. We found that the
      frequency and extent of deletions and additions at the recombination breakpoints
      are similar to those observed at rearranged Ig H chain loci in intact animals.
      The relative frequencies of the types of rearrangements--VD-J, V-DJ, VinvD-J
      (invD = inverted D), and VDJ--however, differ strongly. Moreover, V81x, the most
      used VH gene segment in intact mice, also is overused in this plasmid assay, 15
      to 30 times that of another VH segment. This result indicates that the overuse of
      V81x in the early B cell repertoire can be a consequence of its DNA sequence and
      not of cellular activities.

PMID- 9759864
TI  - Carboxyl-terminal 15-amino acid sequence of NFATx1 is possibly created by tissue
      specific splicing and is essential for transactivation activity in T cells.
AB  - NFAT regulates transcription of a number of cytokine and other immunoregulatory
      genes. We have isolated NFATx, which is one of four members of the NFAT family of
      transcription factors and is preferentially expressed in the thymus and
      peripheral blood leukocytes, and an isoform of NFATx, NFATx1. Here we provide
      evidence showing that 15 amino acids in the carboxyl-terminal end of NFATx1 are
      required for its maximum transactivation activity in Jurkat T cells. A fusion
      between these 15 amino acids and the GAL4 DNA binding domain was capable of
      transactivating reporters driven by the GAL4 DNA binding site. Interestingly,
      this 15-amino acid transactivation sequence is well conserved in NFAT family
      proteins, although the sequences contiguous to the carboxyl-terminal regions of
      the NFAT family are much less conserved. We also report three additional isoforms
      of NFATx, designated NFATx2, NFATx3, and NFATx4. This transactivation sequence is
      altered by tissue-specific alternative splicing in newly isolated NFATx isoforms,
      resulting in lower transactivation activity in Jurkat T cells. NFATx1 is
      expressed predominantly in the thymus and peripheral blood leukocyte, while the
      skeletal muscle expressed primarily NFATx2. In Jurkat cells, transcription from
      the NFAT site of the IL-2 promoter is activated strongly by NFATx1 but only
      weakly by NFATx2. These data demonstrate that the 15-amino acid sequence of
      NFATx1 is a major transactivation sequence required for induction of genes by
      NFATx1 in T cells and possibly regulates NFAT activity through tissue-specific
      alternative splicing.

PMID- 9759866
TI  - Identification of two NF-kappa B sites in mouse CD95 ligand (Fas ligand)
      promoter: functional analysis in T cell hybridoma.
AB  - Fas ligand (FasL) gene expression is critically involved in peripheral T cell
      tolerance and lymphocyte homeostasis. Previous studies have suggested that
      nuclear translocation of NF-kappaB during T cell activation is a critical event
      for FasL gene activation. In the present study we have identified two NF-kappaB
      sites (designated FasL-kappaB1 and FasL-kappaB2) on the promoter (approximately
      700 bp) of FasL. The NF-kappaB sites were identified by electrophoretic mobility
      shift assay. Transient transfection reporter analyses showed that the FasL
      promoter activity was comparable between a construct that contains both sites and
      a shorter construct (433 bp) that contains only the FasL-kappaB1 site.
      Furthermore, elimination of FasL-kappaB1 by site-directed mutagenesis
      significantly inhibited FasL promoter activity. These observations provide strong
      evidence that NF-kappaB directly binds to the FasL-kappaB1 site and up-regulates
      FasL gene expression.

PMID- 9759865
TI  - Role of nuclear factor-kappa B and mitogen-activated protein kinase signaling
      pathways in IL-1 beta-mediated induction of alpha-PDGF receptor expression in rat
      pulmonary myofibroblasts.
AB  - Induction of the alpha-platelet-derived growth factor receptor (PDGF-Ralpha) by
      IL-1beta in lung myofibroblasts enhances mitogenic and chemotactic responses to
      PDGF, and this could be a mechanism of myofibroblast hyperplasia during lung
      fibrogenesis. Since the regulation of many genes by IL-1beta involves activation
      of NF-kappaB and mitogen-activated protein (MAP) kinases, we examined these
      signaling pathways in the control of PDGF-Ralpha expression by IL-1beta in
      cultured rat lung myofibroblasts. Treatment of cells with pyrrolidine
      dithiocarbamate (PDTC), an antioxidant that inhibits NF-kappaB activation,
      completely blocked PDGF-Ralpha up-regulation by IL-1beta as assayed by [125I]PDGF
      AA binding and PDGF-Ralpha mRNA expression, suggesting a role for NF-kappaB.
      However, while IL-1beta and TNF-alpha both induced nuclear binding of the Rel
      proteins p50 and p65 to an NF-kappaB consensus oligonucleotide in gel shift
      assays and caused transient degradation of inhibitor of NF-kappaB-alpha (IkappaB
      alpha) in the cytoplasm of myofibroblasts, only IL-1beta upregulated PDGF-Ralpha.
      These results suggest that NF-kappaB activation alone is not sufficient for up
      regulation of PDGF-Ralpha. An investigation of MAP kinase signaling pathways
      revealed that IL-1beta or PDTC activated extracellular signal-regulated kinase-2
      (ERK-2) and c-jun NH2 terminal kinase-1 (JNK-1) phosphorylation of PHAS-1 and c
      Jun substrates, respectively. Pretreatment of cells with the MAP kinase kinase-1
      (MEK1) inhibitor PD 98059 blocked IL-1beta-induced activation of ERK-2 by more
      than 90% but enhanced IL-1beta-stimulated induction of PDGF-Ralpha expression
      fourfold. Taken together, these data suggest that IL-1beta activates both
      positive and negative signaling pathways that control the expression of PDGF
      Ralpha. IL-1beta appears to mediate its negative effects on PDGF-Ralpha
      expression via MAP kinase activation, while the factor(s) that mediate induction
      of PDGF-Ralpha remain to be elucidated.

PMID- 9759867
TI  - Molecular mapping with functional antibodies localizes critical sites on the
      human IL receptor common gamma (gamma c) chain.
AB  - The IL receptor common gamma (gamma c) chain is required for the formation of
      high affinity cytokine receptor complexes for IL-2, IL-4, IL-7, IL-9, and IL-15,
      and for signals regulating cell survival, growth, and differentiation. Our
      current understanding of how gamma c chain associates with multiple ligands and
      receptor subunits is drawn largely from its structural homology to the human
      growth hormone (hGH) receptor and known structure of the hGH/hGH receptor
      complex. These receptors share distinct features in their extracellular portions
      and are believed to function by a mechanism of ligand-induced association of
      receptor subunits. Here, we report the first directed mutational analysis of the
      human gamma c chain by alanine scanning conducted across seven regions likely to
      contain residues required for intermolecular contact. Functionally distinct,
      neutralizing anti-gamma c mAbs were employed to define critical residues. One
      particular mAb, CP.B8, unique in its ability to inhibit IL-2-, IL-4-, IL-7-, and
      IL-15-induced proliferation and high affinity cytokine binding of normal T cells
      as an intact mAb and as a Fab fragment, localized critical residues to four
      noncontinuous stretches, namely residues in loops AB and EF of domain 1, in the
      interdomain segment, and in loop FG of domain 2. Notably, these residues form a
      contiguous patch on the gamma c chain surface in a three-dimensional structural
      model. These results provide functional evidence for the location of contact
      points on gamma c chain required for its association with multiple ligands.

PMID- 9759868
TI  - Specific antagonism of type I IL-4 receptor with a mutated form of murine IL-4.
AB  - IL-4 is a pleiotropic cytokine that is essential for the differentiation of Th2
      cells and is critically involved in the pathogenesis of certain infectious and
      allergic diseases. We have produced and functionally characterized a mutant of
      murine IL-4 (IL-4.Y119D) as a potential antagonist of IL-4. The analysis of IL-4R
      binding revealed no differences between wild-type and mutated IL-4. Despite this
      finding, IL-4.Y119D was unable to induce proliferation of several IL-4-responsive
      T cell lines mediated via the type I IL-4R (IL-4Ralpha/common gamma chain (gamma
      c chain)) and specifically inhibited the proliferative effect of wild-type IL-4.
      In contrast, with IL-4.Y119D we found induction of MHC class II and CD23
      molecules on resting splenic B cells as well as proliferation of B9 plasmocytoma
      cells. In addition, IL-4.Y119D induced mRNA for soluble IL-4R, leading to the
      release of soluble IL-4R protein by spleen cells. In macrophages, mutated IL-4 in
      combination with IFN-gamma induced TNF-alpha-dependent killing of Leishmania
      major parasites such as wild-type IL-4. The agonistic effects of IL-4.Y119D were
      observed on cells expressing the IL-13R alpha-chain, including an IL-13R alpha
      chain transfected T cell line, but were absent in T cells that lack this
      molecule, indicating that IL-4.Y119D conveys its activity via the type II IL-4R
      (IL-4Ralpha/IL-13Ralpha). The described IL-4 mutant, therefore, represents a new
      tool to use in dissecting different IL-4 functions that are mediated by either
      type I or type II IL-4R complexes.

PMID- 9759869
TI  - Differential transcriptional regulation of CD161 and a novel gene, 197/15a, by IL
      2, IL-15, and IL-12 in NK and T cells.
AB  - Cytokine-mediated enhancement of spontaneous cytotoxicity depends, at least in
      part, on modulation of the expression of surface molecules responsible for
      recognition of target cell structures and triggering or inhibition of the
      cytotoxic machinery. We previously demonstrated that expression of transcription
      factors (e.g., Egr-1, JunB, and c-Fos) is differentially regulated by IL-2 and IL
      12. Here we show that expression of CD161/NKR-P1A, a molecule involved in
      triggering cytotoxicity, is specifically upregulated by IL-12. CD161
      transcription, mRNA accumulation, and surface expression are increased by IL-12.
      Other cytokines sharing the IL-2R beta- and/or common gamma-chains (i.e., IL-15,
      IL-4, and IL-7) do not mediate these effects. In an effort to analyze the
      mechanisms by which IL-2, IL-12, and IL-15 differentially regulate gene
      transcription, we have isolated a novel gene, 197/15a, the expression of which in
      NK and T cells is down-regulated by IL-2 and IL-15, up-regulated by IL-12, and
      not affected by IL-4 and IL-7. IL-2 and IL-15 act, at least in part, repressing
      197/15a transcription; their effect on 197/15a mRNA accumulation is partially
      independent of novel protein synthesis, likely not mediated by JunB, Bcl-2, or
      Bax, and requires the activity of rapamycin-sensitive molecule(s). The
      observation that IL-2 and IL-12 differentially modulate CD161 expression suggests
      the existence of cytokine-specific mechanisms of modulation of spontaneous
      cytotoxicity based on the regulation of expression of surface molecules involved
      in target cell recognition and/or triggering of the cytolytic machinery.

PMID- 9759870
TI  - The molecular and functional characterization of a dominant minor H antigen, H60.
AB  - Minor histocompatibility (H) Ags elicit T cell responses and thereby cause
      chronic graft rejection and graft-vs-host disease among MHC identical
      individuals. Although numerous independent H loci exist in mice of a given MHC
      haplotype, certain H Ags dominate the immune response and are thus of
      considerable conceptual and therapeutic importance. To identify these H Ags and
      their genes, lacZ-inducible CD8+ T cell hybrids were generated by immunizing
      C57BL/6 (B6) mice with MHC identical BALB.B spleen cells. The cDNA clones
      encoding the precursor for the antigenic peptide/Kb MHC class I complex were
      isolated by expression cloning using the BCZ39.84 T cell as a probe. The cDNAs
      defined a new H locus (termed H60), located on mouse chromosome 10, and encoded a
      novel protein that contains the naturally processed octapeptide LTFNYRNL (LYL8)
      presented by the Kb MHC molecule. Southern blot analysis revealed that the H60
      locus was polymorphic among the BALB and the B6 strains. However, none of the H60
      transcripts expressed in the donor BALB spleen were detected in the host B6
      strain. The expression and immunogenicity of the LYL8/Kb complex in BALB.B and
      CXB recombinant inbred strains strongly suggested that the H60 locus may account
      for one of the previously described antigenic activity among these strains. The
      results establish the source of an immunodominant autosomal minor H Ag that, by
      its differential transcription in the donor vs the host strains, provides a novel
      peptide/MHC target for host CD8+ T cells.

PMID- 9759871
TI  - B cell responses to a peptide epitope. V. Kinetic regulation of repertoire
      discrimination and antibody optimization for epitope.
AB  - The influence of imposing various conformational constraints on immune responses
      to a model epitope within a synthetic peptide immunogen was examined in mice.
      Although overall immunogenicity was affected, the model epitope (sequence DPAF)
      remained the predominant recognition site regardless of the conformation in which
      it was presented. A comparison of anti-DPAF mAbs obtained in response to two
      analogue peptides, PS1CT3 and CysCT3, in which the DPAF segment was either
      unconstrained or held within a cyclic loop, respectively, revealed a significant
      homology in the paratope composition. At one level a subset of anti-PS1CT3 and
      anti-CysCT3 mAbs was found to share a common heavy chain variable region. In
      addition, nucleotide sequence homology comparisons of both heavy and light chain
      variable regions identified the presence of anti-PS1CT3 and anti-CysCT3 mAbs that
      collectively appeared to derive from a common progenitor, but with nonidentical
      somatic mutations. Interestingly, however, no bias toward homologous Ag could be
      discerned on measurement of relative affinities of the mAbs for the two peptides.
      In contrast, mAb binding on-rates clearly discriminated between peptides
      representing the homologous vs the heterologous confomer of the DPAF epitope.
      Thus, it would appear that the kinetics of Ag recognition dominate over
      equilibrium binding criteria both in epitope-driven repertoire selection and Ab
      maturation in a humoral response.

PMID- 9759872
TI  - Characterization of human gamma 4 switch region polymorphisms suggests a meiotic
      recombinational hot spot within the Ig locus: influence of S region length on
      IgG4 production.
AB  - Human gamma4 gene RFLPs, revealed after BamHI digestion, show IGHG4 alleles of
      9.0 (9.2), 9.4, and 9.6 kb at various frequencies in different ethnic
      populations. Studies in immunodeficient individuals have previously suggested
      that the 9.4 BamHI allele is associated with a higher serum level of IgG4 than
      the 9.0 (9.2) BamHI allele, but it is not clear whether this is associated with
      the S region itself or other control elements. In addition, a duplication of the
      9.4-kb gamma4 allele has recently been observed in a high proportion of normal
      donors. We therefore undertook a study of the structural basis for the difference
      in Ab levels in the various gamma4 alleles. We demonstrate that the Sgamma4
      alleles differ in length due to deletions and insertions of a varying number of
      79-bp Sgamma4 repeat units. Two novel RFLPs, 8.8 and 9.1 kb, were also observed.
      The alleles are likely to be generated by unequal crossing over, and the
      breakpoints cluster in Sgamma4 repeat units that contain chi-like motifs,
      implicating chi-like sequences in the meiotic recombination. Our data support the
      idea that the 9.4-kb BamHI allele is more productive than the 9.0 (9.2)-kb allele
      in normal healthy donors, possibly due to the extended switch regions, whereas
      duplication of the gamma4 gene has no effect on switching and IgG4 serum levels.

PMID- 9759873
TI  - Structural basis of specificity and degeneracy of T cell recognition:
      pluriallelic restriction of T cell responses to a peptide antigen involves both
      specific and promiscuous interactions between the T cell receptor, peptide, and
      HLA-DR.
AB  - TCR engagement of peptide-MHC class II ligands involves specific contacts between
      the TCR and residues on both the MHC and peptide molecules. We have used
      molecular modeling and assays of peptide binding and T cell function to
      characterize these interactions for a CD4+ Th1 cell clone, ESL4.34, which
      recognizes a peptide epitope of the herpes simplex type 2 virus virion protein,
      VP16 393-405, in the context of several HLA-DR alleles. This clone responded to
      VP16 393-405 in proliferation and cytotoxicity assays when presented by
      DRB1*0402, DRB1*1102, and DRB1*1301, which share a common amino acid sequence,
      ILEDE, at residues 67-71 in the alpha-helical portion of the DRbeta polypeptide,
      but not when presented by other DR4, DR11, and DR13 alleles that are negative for
      this sequence. Using a panel of APCs expressing DR4 molecules that were
      mutagenized in vitro at individual residues within this shared epitope and using
      peptide analogues with single amino acid substitutions of predicted MHC and TCR
      contact residues, a unit of recognition was identified dependent on DRbeta
      residues 67-71 and relative position 4 (P4) of the VP16 393-405 peptide. The
      interactions of this portion of the peptide-DR ligand with the ESL4.34 TCR
      support a structural model for MHC-biased recognition in some Ag-specific and
      alloreactive T cell responses and suggest a possible mechanism for autoreactive T
      cell selection in rheumatoid arthritis.

PMID- 9759874
TI  - Up-regulation by ammonium trichloro(dioxoethylene-0,0') tellurate (AS101) of
      Fas/Apo-1 expression on B16 melanoma cells: implications for the antitumor
      effects of AS101.
AB  - It was recently reported that human and mouse melanoma cells express Fas ligand
      (FasL) but almost no Fas, which may contribute to their immune privilege. AS101
      (ammonium trichloro(dioxoethylene-0,0')tellurate), a synthetic immunomodulator
      with minimal toxicity, was found to have antitumor effects in various tumor
      models. Our present study shows that AS101 has direct and indirect effects on
      tumor cells; AS101 inhibits the clonogenicity of B16 melanoma cells in vitro.
      Moreover, wild-type P53 expression, which is required for induction of Apo-1
      expression, increased significantly in AS101-treated cells. We therefore
      investigated Fas expression in AS101-treated B16 cells and found that Fas, but
      not FasL, expression was significantly increased; moreover, Fas receptors were
      functional. Longer incubation with AS101 resulted in spontaneous apoptosis
      triggered by the Fas-FasL system. To explore the relationship of these results to
      the antitumor effects of AS101, we injected B16-F10 mouse melanoma cells into
      syngeneic C57BL/6 mice carrying the lpr mutation in the Fas gene and to gld
      mutant mice that lack functional FasL. Tumor development in control groups was
      lowest in the lpr mice, while no difference was observed between gld and wild
      type mice. Among the AS101-treated groups, the most pronounced effect appeared in
      the lpr mice, while the lowest was seen in the gld mutant mice. Our study
      suggests that AS101 may render melanoma tumor cells more sensitive to Fas/FasL
      induced apoptosis and may therefore have clinical potential.

PMID- 9759875
TI  - IFN-gamma is required for IL-12 responsiveness in mice with Candida albicans
      infection.
AB  - To elucidate the role of IFN-gamma in antifungal CD4+ Th-dependent immunity,
      129/Sv/Ev mice deficient for IFN-gamma receptor (IFN-gammaR(-/-)) were assessed
      for susceptibility to gastrointestinal or systemic Candida albicans infection and
      for parameters of innate and adaptive T helper immunity. IFN-gammaR(-/-) mice
      failed to mount protective Th1-mediated acquired immunity upon mucosal
      immunization or in response to a live vaccine strain of the yeast. The impaired
      Th1-mediated resistance correlated with defective IL-12 responsiveness, but not
      IL-12 production, and occurred in the presence of an increased innate antifungal
      resistance. The development of nonprotective Th2 responses was observed in IFN
      gammaR(-/-) mice upon mucosal infection and subsequent reinfection. However,
      under experimental conditions of Th2 cell activation, the occurrence of Th2 cell
      responses was similar in IFN-gammaR(-/-) and in IFN-gammaR(+/+) mice. These
      results indicate the complex immunoregulatory role of IFN-gamma in the induction
      of mucosal and nonmucosal anticandidal Th cell responses; IFN-gamma is not
      essential for the occurrence of Th2 responses but is required for development of
      IL-12-dependent protective Th1-dependent immunity.

PMID- 9759876
TI  - lck-independent inhibition of T cell antigen response by the HIV gp120.
AB  - Binding of the HIV envelope glycoprotein gp120 to CD4 inhibits T cell activation.
      We have used a murine T cell clone transfected with either wild-type human CD4 or
      mutated forms of CD4 to characterize the pathways involved in this inhibitory
      effect of gp120. Ag-induced proliferation of T cell clones transfected with human
      CD4 was completely inhibited in the presence of gp120, even though stimulation of
      this clone is independent of a CD4/MHC class II interaction. In addition, our
      results demonstrate that the inhibition by gp120 is not due to the sequestration
      of lck from TCR and does not require activation of lck by gp120. This suggests
      that CD4 can regulate the initiation of T cell activation independently of its
      interaction with lck. Moreover, we demonstrate that the nonresponsiveness induced
      by gp120 can be reversed by soluble CD4 when added early after onset of
      stimulation and that gp120 exerts its inhibitory effect when cells are in the G0
      > or = 1 phase of the cell cycle.

PMID- 9759877
TI  - Monoclonal antibodies reveal additional epitopes of serotype D Cryptococcus
      neoformans capsular glucuronoxylomannan that elicit protective antibodies.
AB  - Epitope specificity and isotype influence mAb efficacy against Cryptococcus
      neoformans; however, the relative contribution of each attribute is poorly
      understood. To date, only mAbs that recognize two epitopes of capsular
      glucuronoxylomannan (GXM), defined by the IgG1 mAbs 2H1 and E1, consistently
      mediate protection against C. neoformans. The role of epitope specificity was
      further examined using six additional IgG1 mAbs and serotype D C. neoformans ATCC
      24067. mAbs 3C2, 439, and 471 recognize the 2H1 epitope, whereas mAbs 339, 1255,
      and 302 recognize two separate epitopes. mAbs 3C2, 439, and 471 competed for GXM
      with the IgA mAb 18G9, a 2H1 mAb family member, whereas mAbs 302, 339, and 1255
      did not. Each mAb bound GXM similarly, as determined by agglutination, direct Ag
      binding, Ag inhibition, and indirect capsular immunofluorescence assays. mAb
      apparent affinity constants for GXM ranged from 5 to 26 x 10(7) M(-1) with mAb
      1255 > 3C2 > 339 > 439 > 471 > 302. Each mAb significantly prolonged survival (p
      < 0.05); the average survival times of control and mice passively immunized with
      mAbs 3C2, 302, 339, 439, 471, and 1255 were 10.8, 36.6, 33, 25.5, 24.9, 17, and
      22.6 days, respectively. Although each mAb enhanced J774.16 cell fungicidal
      activity, differences were observed in the ability of each mAb to facilitate
      attachment and ingestion of cryptococci. These results indicate 1) two additional
      epitope specificities associated with mAb efficacy, 2) differences in opsonic and
      protective efficacy for IgG1 anti-GXM mAbs, 3) an association between affinity
      and protective efficacy, and 4) additional support for association between an
      annular indirect capsular immunofluorescence pattern and mAb efficacy.

PMID- 9759878
TI  - Oxidant stress incites spreading of macrophages via extracellular signal
      regulated kinases and p38 mitogen-activated protein kinase.
AB  - Cultured macrophages exhibit spreading in response to external stimuli. It is
      relevant to in vivo morphologic changes of macrophages during extravasation,
      migration, and differentiation. The present study was performed to elucidate
      molecular mechanisms that regulate spreading of macrophages. Redox is a crucial
      factor that modulates a wide range of cell function. We found that macrophages
      undergo spreading in response to oxidant stress caused by hydrogen peroxide or an
      oxidant generating agent menadione. To identify signaling pathways involved, a
      role of mitogen-activated protein (MAP) kinases was investigated. Western blot
      analysis showed that treatment of macrophages with menadione rapidly induced
      phosphorylation of extracellular signal-regulated kinases (ERK1, ERK2) and p38
      MAP kinase, but not c-Jun N-terminal kinase (JNK). Pharmacologic inhibition of
      either ERK or p38 activation blunted the macrophage spreading. Similarly,
      transfection with dominant-negative mutants of ERKs or a mutant p38 significantly
      suppressed the oxidant-triggered spreading. ERKs and p38 are known to activate
      serum response element (SRE) via phosphorylation of the ternary complex factor
      Elk-1. To further identify downstream events, we focused on a role of SRE.
      Stimulation of macrophages with menadione induced activation of SRE. Intervention
      in the SRE activation by a dominant-negative mutant of Elk-1 inhibited the
      menadione-induced spreading. These results suggest that oxygen radical
      metabolites, the well-known mediators for tissue injury, incite spreading of
      macrophages via the MAP kinase-SRE signaling pathways.

PMID- 9759879
TI  - In vivo and in vitro activities of the gp130-stimulating designer cytokine Hyper
      IL-6.
AB  - IL-6 is a multifactorial cytokine mediating acute inflammatory responses in the
      liver. When IL-6 binds to a specific receptor (IL-6R), the IL-6/IL-6R complex
      associates with the signal transducer gp130, initiating intracellular signaling.
      A soluble form of the IL-6R (sIL-6R) renders target cells sensitive to IL-6 that
      do not express the IL-6R on their surfaces. A designer cytokine, termed Hyper-IL
      6, consisting of IL-6 covalently linked to the sIL-6R was fully active on gp130
      expressing cells at 100- to 1000-fold lower concentrations than unlinked IL-6 and
      IL-6R. Mice were injected i.p. with Hyper-IL-6 or IL-6. Upon injection of Hyper
      IL-6 into mice, the acute phase response, as measured by haptoglobin mRNA
      expression in the liver, was markedly increased and lasted significantly longer
      compared with that in mice injected with a 10-fold higher dose of IL-6 alone. On
      human hepatoma cells, Hyper-IL-6 caused similar effects, indicating that the
      longer lasting response to the fusion protein could not only be explained by the
      longer plasma half-life of the fusion protein. Experiments using iodinated IL-6
      and Hyper-IL-6 revealed that Hyper-IL-6 bound with high affinity to gp130 and was
      less efficiently internalized. This effect might explain the longer lasting
      activity of this protein on cells. The highly active IL-6/sIL-6R designer protein
      might be of significant clinical importance for the stimulation of cells that are
      more responsive to the IL-6/sIL-6R complex than to IL-6 alone. Such cells include
      hemopoietic progenitor cells and hepatocytes.

PMID- 9759880
TI  - Down-regulation of CD1 on antigen-presenting cells by infection with
      Mycobacterium tuberculosis.
AB  - Intracellular pathogens have developed efficient evasion strategies to survive
      the defenses of the host immune system. In this study, we describe a new escape
      mechanism utilized by Mycobacterium tuberculosis that involves the down
      regulation of the Ag-presenting molecule CD1 from the cell surface of CD1+ APCs.
      The loss of CD1 from the cell surface is associated with a complete inhibition of
      the ability of the infected cells to present Ag to CD1-restricted T cells. The
      down-regulation of Ag-presenting molecules on CD1+ APC by infection with M.
      tuberculosis is unique for CD1, since the expression of the classical Ag
      presenting molecules MHC class I and MHC class II is not influenced. Our data
      show that efficient down-regulation of CD1 requires infection of the cells with
      live mycobacteria, since heat killing of the bacteria completely abrogates the
      effect. The observed down-regulation is not due to the secretion of cytokines or
      other host- or pathogen-derived factors. Investigation of upstream events
      responsible for the down-regulation of CD1 revealed that infection with live M.
      tuberculosis decreased the steady state CD1-mRNA levels. This study introduces a
      novel evasion mechanism of M. tuberculosis that could contribute to persistence
      of intracellular infection by avoiding immune recognition.

PMID- 9759881
TI  - Characterization of a peptide analog of a determinant of type II collagen that
      suppresses collagen-induced arthritis.
AB  - Immunization of susceptible strains of mice with type II collagen (CII) elicits
      an autoimmune arthritis known as collagen-induced arthritis (CIA). One analogue
      peptide of the immunodominant T cell determinant, A9 (CII245-270 (I260-->A, A261-
      >B, F263-->N)), was previously shown to induce a profound suppression of CIA when
      coadministered at the time of immunization with CII. In the present study, A9
      peptide was administered i.p., orally, intranasally, or i.v. 2 to 4 wk following
      CII immunization. We found that arthritis was significantly suppressed even when
      A9 was administered after disease was induced. To determine the mechanism of
      action of A9, cytokine responses to A9 and wild-type peptide A2 by CII-sensitized
      spleen cells were compared. An increase in IL-4 and IL-10, but not in IFN-gamma,
      was found in A9 culture supernatants. Additionally, cells obtained from A9
      immunized mice produced higher amounts of IL-4 and IL-10 when cultured with CII
      compared with cells obtained from mice immunized with A2, which produced
      predominantly IFN-gamma. Suppression of arthritis could be transferred to naive
      mice using A9-immune splenocytes. Lastly, phosphorylation of TCRzeta was not
      altered in the immunoprecipitates from the lysates of cells exposed to analogue
      peptides (A9 and A10) together with wild-type A2 in a T cell line and two I-Aq
      restricted, CII-specific T hybridomas. We conclude that analogue peptide A9 is
      effective in suppressing established CIA by inducing T cells to produce a Th2
      cytokine pattern in response to CII.

PMID- 9759882
TI  - A breast and melanoma-shared tumor antigen: T cell responses to antigenic
      peptides translated from different open reading frames.
AB  - Infusion of TIL586 along with IL-2 into the autologous patient with metastatic
      melanoma resulted in the objective regression of tumor. Here, we report that
      screening a cDNA library from the 586mel cell line using CTL clones derived from
      TIL586 resulted in the isolation of a gene, CAG-3 (cancer Ag gene 3). Sequence
      analysis revealed that CAG-3 encodes an open reading frame identical to NY-ESO-1,
      which was recently reported to be recognized by autologous serum from a patient
      with esophageal cancer. Thus, NY-ESO-1 appears to be an immune target for both Ab
      and T cell-mediated responses. Significantly, NY-ESO-1-specific CTL clones were
      capable of recognizing two HLA-A31-positive fresh and cultured breast tumors. To
      our knowledge, this represents the first direct demonstration that tumor-specific
      CTL clones can recognize both breast and melanoma tumor cells. A 10-mer antigenic
      peptide ESO10-53 (ASGPGGGAPR) was identified from the normal open reading frame
      of NY-ESO-1 based on its ability to sensitize HLA-A31-positive target cells for
      cytokine release and specific lysis. Interestingly, two additional CTL clones
      that were sensitized with NY-ESO-1 recognized two overlapping antigenic peptides
      derived from an alternative open reading frame of the same gene. These findings
      indicate that CTLs simultaneously responded to two different gene products
      translated from the normal and alternative reading frames of the same gene.
      Understanding of this mechanism by which the alternative reading frame is
      translated may have important implications in tumor immunology.

PMID- 9759884
TI  - Controlled lipidation and encapsulation of peptides as a useful approach to
      mucosal immunizations.
AB  - To generate a useful strategy for mucosal immunization, we have developed an
      approach of lipidating a multiple Ag peptide (MAP) containing part of the V3 loop
      from HIV-1 gp120IIIB. In this work, we compare two delivery systems, lipidated
      MAP in PBS and encapsulation in poly(DL-lactide-co-glycolide) microparticles.
      Subcutaneous immunization, followed by intragastric administration of MAP peptide
      entrapped or not entrapped in microparticles, induced mucosal and systemic immune
      responses at local and distant sites, including mucosal IgA in saliva, vaginal
      secretions and feces, and IgG in blood. However, lipidated Ag delivered in
      microparticles induced higher levels of mucosal Abs, particularly of intestinal
      IgA, and generated CTL responses. In contrast, lipidated MAP delivered by nasal
      route microparticles was less effective in inducing CTL responses. These results
      demonstrate the feasibility of using a lipidated multimeric peptide for mucosal
      immunization to stimulate both systemic and mucosal immune systems, including the
      genital tract, irrespective of the route or method of delivery and without
      requiring the use of a carrier or an extraneous adjuvant.

PMID- 9759883
TI  - A synthetic lipopolysaccharide-binding peptide based on amino acids 27-39 of
      serum amyloid P component inhibits lipopolysaccharide-induced responses in human
      blood.
AB  - LPS-binding proteins in plasma play an important role in modifying LPS toxicity.
      Significant properties have already been attributed to the LPS-binding protein
      (LBP). It accelerates LPS toxicity as well as incorporation into high-density
      lipoproteins, leading to neutralization of LPS in serum. A search for other LPS
      binding components in serum, using LPS-coated magnetic beads, revealed a new LPS
      binding protein. N-terminal microsequencing identified this protein as serum
      amyloid P component (SAP). Purified SAP bound to smooth and rough types of LPS
      via the lipid A part. SAP inhibited the binding of FITC-labeled ReLPS (LPS from
      Salmonella minnesota strain R595) to human monocytes and the ReLPS-induced
      priming of the oxidative burst of human neutrophils only in the presence of low
      concentrations of LBP. In search for the LPS binding site of SAP, we found that
      pep27-39, a 13-mer peptide consisting of amino acids 27-39 of SAP, competitively
      inhibited the binding of LPS to SAP. In addition, pep27-39 significantly
      inhibited ReLPS-induced responses in phagocytes in the presence of serum, as well
      as in human whole blood. Carboxamidomethylated pep27-39 showed an even more
      pronounced reduction of the ReLPS-induced priming of phagocytes in human blood.
      Performing gel filtration of FITC-labeled ReLPS incubated with soluble CD14, we
      showed that SAP could not prevent binding of LPS to soluble CD14, in contrast to
      pep27-39. The ability of pep27-39 to antagonize specifically the effects of LPS
      in the complex environment of human blood suggests that pep27-39 may be a novel
      therapeutic agent in the treatment of gram-negative sepsis.

PMID- 9759886
TI  - Inhibition of leukocyte emigration induced during the systemic inflammatory
      reaction in vivo is not due to IL-8.
AB  - In keeping with the multistep model of leukocyte-endothelial cell interaction,
      stimulation of endothelium by cytokines or endotoxin (LPS) in vitro leads to
      selectin/integrin-mediated neutrophil adhesion, followed by neutrophil
      endothelial transmigration. The i.p. injection of LPS in vivo induces a systemic
      inflammatory reaction in a mouse model with generalized activation of both
      endothelial cells (up-regulation of adhesion molecules ICAM-1, VCAM-1, E
      selectin) and neutrophils (up-regulation of Mac-1). However, no intravascular
      endothelial adhesion or tissue emigration of neutrophils can be observed. Even
      more importantly, the in vivo emigration of polymorphonuclear cells at sites of a
      local inflammatory reaction (IL-8, TNF, LPS) is totally inhibited when the mice
      are pretreated systemically with LPS, although the neutrophils respond fully to a
      rechallenge with LPS ex vivo, and endothelial adhesion molecules are further up
      regulated locally. The systemic application of TNF also caused a total inhibition
      of neutrophil emigration. However, while anti-TNF mAb abrogated the inhibitory
      activity induced by TNF, they had no effect on systemic LPS. The systemic
      application of IL-8 did not inhibit neutrophil emigration, nor did the
      pretreatment of mice with anti-IL-8 mAb before the systemic application of LPS
      abrogate the inhibitory activity induced by LPS. Therefore, the putative
      inhibitor of neutrophil emigration, which may be of great physiologic importance,
      as it prevents in vivo the generalized emigration of activated neutrophils, most
      likely is not IL-8.

PMID- 9759885
TI  - Stem cell factor augments Fc epsilon RI-mediated TNF-alpha production and
      stimulates MAP kinases via a different pathway in MC/9 mast cells.
AB  - Mast cells express the receptor tyrosine kinase kit/stem cell factor receptor
      (SCFR) which is encoded by the proto-oncogene c-kit. Ligation of SCFR induces its
      dimerization and activation of its intrinsic tyrosine kinase activity leading to
      activation of Raf-1, phospholipases, phosphatidylinositol 3-kinase, and
      extracellular signal-regulated kinases. However, little is known about the
      downstream signals initiated by SCFR ligation except for activation of
      extracellular signal-regulated kinases. The murine mast cell line, MC/9,
      synthesizes and secretes TNF-alpha following the aggregation of high affinity Fc
      receptors for IgE (Fc epsilonRI). Ligation of SCFR or Fc epsilonRI on MC/9 cells
      resulted in the activation of all three MAP kinase family members, extracellular
      signal-regulated kinases, c-Jun amino-terminal kinase (JNK), and p38. Stem cell
      factor (SCF)-induced activation of JNK and p38 was insensitive to wortmannin,
      cyclosporin A, and FK506 whereas activation of these kinases through Fc epsilonRI
      was sensitive to these drugs. Coligation of SCFR augmented Fc epsilonRI-mediated
      activation of MAP kinases, especially JNK activation, and SCF augmented Fc
      epsilonRI-mediated TNF-alpha production in MC/9 cells, although SCF alone did not
      induce TNF-alpha production. This augmentation by SCF was regulated at the level
      of transcription, at least in part, since the promoter activity of TNF-alpha was
      enhanced following addition of SCF. These results demonstrate that SCF can
      augment Fc epsilonRI-mediated JNK activation and cytokine gene transcription but
      via pathways that are regulated differently than the ones activated through Fc
      epsilonRI.

PMID- 9759887
TI  - Protection from collagen-induced arthritis in granulocyte-macrophage colony
      stimulating factor-deficient mice.
AB  - The involvement of granulocyte-macrophage CSF (GM-CSF) in collagen-induced
      arthritis (CIA) was examined using GM-CSF-deficient mice. Although CIA is
      generally considered to be restricted to mice of the H-2q or H-2r haplotypes, we
      examined the role of GM-CSF in the CIA model using GM-CSF-deficient (-/-) and
      wild-type (+/+) mice on a C57BL/6 (H-2b) background. Mice were immunized by
      intradermal injection at the base of the tail with chick type II collagen
      followed by a repeat injection 21 days later. We found, based on both clinical
      and histologic assessments, that wild-type mice on this background developed
      severe CIA, while the GM-CSF-deficient mice had virtually no disease. Mice that
      were heterozygous for the GM-CSF gene (+/-) collectively displayed an
      intermediate response between those of the GM-CSF(+/+) and GM-CSF(-/-) groups,
      suggesting a gene dosage effect. GM-CSF(+/+) and GM-CSF(+/-) mice exhibited CIA
      responses ranging from mild (single digits) to severe swelling of all four paws,
      while in the few GM-CSF(-/-) mice that developed CIA the disease was confined to
      single digits. Despite the putative role of GM-CSF in dendritic cell development,
      GM-CSF-deficient mice exhibited both humoral and cellular (delayed-type
      hypersensitivity) responses to type II collagen; however, the cellular response
      was significantly reduced in the GM-CSF-deficient mice compared with the wild
      type controls. These findings suggest that GM-CSF is required for CIA development
      in mice and support the idea that GM-CSF is a key cytokine in inflammatory joint
      disease.

PMID- 9759888
TI  - Dust mite proteolytic allergens induce cytokine release from cultured airway
      epithelium.
AB  - Endogenous proteolytic enzymes have been shown to be potential sources of airway
      inflammation inducing proinflammatory cytokine release from respiratory
      epithelial cells; however, whether any of the exogenous proteases from important
      allergen sources such as the house dust mite present in our environment behave in
      a similar fashion is unclear. To this end, we have investigated whether the mite
      cysteine and serine proteolytic allergens, Der p 1 and Der p 9, respectively,
      induced cytokine production from primary human bronchial epithelial cells and
      from the epithelial cell line BEAS-2B. Cells were exposed to mite proteases, and
      cells or supernatants were assayed for cytokine release, cytokine mRNA
      expression, and modulation of intracellular calcium ion concentration. Both
      proteases induced concentration- and time-dependent increases in the release of
      granulocyte-macrophage (GM)-CSF, IL-6, and IL-8 as well as an increase in the
      expression of IL-6 mRNA. Cytokine release and mRNA expression were first observed
      at 8 h and 2 h after protease exposure, respectively. The minimum concentration
      of each protease that was required to stimulate GM-CSF, IL-6, and IL-8 release
      was approximately 10 ng/ml. Cytokine release was initiated by 1 to 2 h of
      protease exposure, although maximum concentrations were detected only after a 24
      h incubation. IL-6, but not IL-8 and GM-CSF, was shown to be degraded by both
      proteases at concentrations of > 2 microg/ml. The proteases also stimulated
      changes in the intracellular calcium ion concentration. All mite protease-induced
      phenomena were inhibited using appropriate protease inhibitors. These results
      suggest that the proteolytic activity of an allergen may stimulate the release of
      proinflammatory cytokines from human bronchial epithelium.

PMID- 9759889
TI  - Stromal cell-derived factor-1 alpha and stem cell factor/kit ligand share
      signaling pathways in hemopoietic progenitors: a potential mechanism for
      cooperative induction of chemotaxis.
AB  - Stromal cell-derived factor (SDF-1alpha), the ligand for CXCR4, is a chemokine
      that acts as a potent chemoattractant for hemopoietic progenitor cells. Stem cell
      factor/kit ligand (SCF/KL), an early acting cytokine, has recently been reported
      to enhance the chemotaxis induced by SDF-1alpha. However, very little is known
      about downstream signaling events following these receptor-ligand interactions.
      To investigate these events, we utilized a model progenitor cell line, CTS, which
      expresses both the CXCR4 and c-kit receptors. We observed strong Ca2+
      mobilization and enhancement of chemotaxis following treatment with SDF-1alpha or
      SCF/KL. A combination of these factors enhanced this chemotaxis in CTS cells as
      well as in CD34+ bone marrow cells. Prior treatment of CTS cells with pertussis
      toxin inhibited the SDF-1alpha-induced chemotaxis, suggesting that SDF-1alpha
      signaling involves a pertussis-sensitive Gi-coupled protein. SDF-1alpha treatment
      resulted in a rapid phosphorylation of the focal adhesion molecules RAFTK
      (related adhesion focal tyrosine kinase), paxillin, and p130cas, which then
      declined within minutes. SCF/KL alone or in combination with SDF-1alpha induced a
      rapid and sustained effect on phosphorylation of these substrates. SDF-1alpha
      treatment resulted in a rapid and robust activation of p44/42 mitogen-activated
      protein kinase compared with the relatively weak and delayed effect of SCF/KL
      treatment. Interestingly, a delayed but sustained activation of mitogen-activated
      protein kinase activation was observed when the factors were used in combination.
      Such cooperativity in downstream signaling pathways may explain the enhanced
      chemotaxis of progenitors observed with SDF-1alpha in combination with SCF/KL.

PMID- 9759890
TI  - Lipopolysaccharide-induced desensitization of junB gene expression in a mouse
      macrophage-like cell line, P388D1.
AB  - Treatment of a mouse macrophage cell line, P388D1, for 1 h with bacterial LPS
      caused a transient increase in the level of junB mRNA expression. These cells
      became refractory in terms of the junB gene response to exposure to a second
      round of LPS or lipid A, but not to PMA. The LPS-induced desensitized state was
      not due to the shortening of the half-life of junB mRNA, but was suggested, by
      nuclear run-on analysis, to be caused by reduction of junB gene transcription.
      Pretreating cells with herbimycin A, a tyrosine kinase inhibitor, substantially
      inhibited LPS-induced expression of junB mRNA and decreased tyrosine
      phosphorylation of 38- to 42-kDa proteins, which comigrated with p38 and p42
      mitogen-activated protein (MAP) kinases. Parallel to down-regulation of junB mRNA
      expression, activation of the p38 MAP kinase was markedly reduced in LPS-tolerant
      cells, whereas activation of p42 MAP kinase was relatively constant. The specific
      p38 MAP kinase inhibitor, SB202190, potently inhibited LPS-induced junB mRNA
      expression. These results suggest that the LPS-induced desensitization of junB
      gene expression occurs at or upstream of the level of gene transcription and may
      be involved in a defective LPS-induced p38 MAP kinase pathway.

PMID- 9759891
TI  - Modulation of human neutrophil apoptosis by immune complexes.
AB  - In the present study we examined whether immune complexes (IC) are able to
      modulate human neutrophil apoptosis. We observed different effects depending on
      the type of IC employed. Precipitating IC (pIC) and Ab-coated erythrocytes (E
      IgG) triggered a marked stimulation of apoptosis, while heat-aggregated IgG and
      soluble IC, significantly delayed spontaneous apoptosis. Blocking Abs directed to
      Fcgamma receptor type II (FcgammaRII), but not to FcgammaRIII, markedly
      diminished the acceleration of apoptosis triggered by either pIC or E-IgG,
      supporting a critical role for FcgammaRII in apoptosis stimulation. This
      phenomenon, on the other hand, does not appear to involve IC phagocytosis or the
      participation of CR3. Acceleration of neutrophil apoptosis triggered by either
      pIC or E-IgG seems to require the activation of the respiratory burst, as
      suggested by 1) the ability of catalase to prevent apoptosis stimulation; 2) the
      effect of azide, an heme enzyme inhibitor, which dramatically enhanced apoptosis
      induced by pIC or E-IgG; and 3) the inability of pIC or E-IgG to accelerate
      apoptosis of neutrophils isolated from CGD patients. It is well established that
      IC affect the course of inflammation by inducing the release of inflammatory
      cytokines, proteolytic enzymes, oxidative agents, and other toxic molecules. Our
      results suggest that IC may also affect the course of inflammation by virtue of
      their ability to modulate neutrophil apoptosis.

PMID- 9759892
TI  - The regulation and functional consequence of proinflammatory cytokine binding on
      human intestinal epithelial cells.
AB  - Products of an activated immune system may affect cells within the immune system
      as well as nonlymphoid cells in the local environment. Given the immunologically
      activated state of the intestinal tract, it is conceivable that locally produced
      cytokines could regulate epithelial cell function. To assess whether epithelial
      cells are targets for particular cytokines, we initiated studies on the binding
      of a panel of proinflammatory cytokines in freshly isolated epithelial cells from
      normal and inflammatory bowel disease (IBD) patients as well as in cell lines.
      Isolated intestinal epithelial cells (IEC) were stained with phycoerythrin
      conjugated or biotinylated cytokines to determine the expression and density of
      receptors for IL-1beta, IL-6, granulocyte-macrophage CSF (GM-CSF), and TNF-alpha.
      Receptors for IL-1beta, IL-6, and GM-CSF were readily detectable in all
      epithelial cell preparations at levels equal to (GM-CSFR) or lower than those
      seen on monocytes. However TNFalpha-R were not detectable on freshly isolated
      IECs. Receptor density was greater in surface vs crypt epithelial cells, but no
      significant differences were seen between normal and IBD epithelial cells.
      Expression of IL-1R and IL-6R was enhanced by LPS and IFN-gamma. Functionally, IL
      1beta enhanced proliferation of the IEC cell line, DLD1, whereas GM-CSF treatment
      of de-differentiated crypt-like DLD1 and HT29 cells resulted in enhanced
      expression of ICAM-1. Furthermore, TNF-alpha treatment enhanced the secretion of
      IL-8 and GRO-alpha in HT29 cells, but not in freshly isolated IEC cultures. The
      differential binding and function of proinflammatory cytokines on IEC support the
      hypothesis that these cytokines may be involved in normal physiological processes
      as well as in regulating mucosal immune responses.

PMID- 9759893
TI  - Soluble ICAM-1 activates lung macrophages and enhances lung injury.
AB  - Because of the important role of rat ICAM-1 in the development of lung
      inflammatory injury, soluble recombinant rat ICAM-1 (sICAM-1) was expressed in
      bacteria, and its biologic activities were evaluated. Purified sICAM-1 did bind
      to rat alveolar macrophages in a dose-dependent manner and induced production of
      TNF-alpha and the CXC chemokine, macrophage inflammatory protein-2 (MIP-2).
      Alveolar macrophages exhibited cytokine responses to both sICAM-1 and immobilized
      sICAM-1, while rat PBMCs failed to demonstrate similar responses. Exposure of
      alveolar macrophages to sICAM-1 resulted in NFkappaB activation (which was
      blocked by the presence of the aldehyde peptide inhibitor of 28S proteosome and
      by genistein, a tyrosine kinase inhibitor). As expected, cross-linking of CD18 on
      macrophages with Ab resulted in generation of TNF-alpha and MIP-2. This response
      was also inhibited in the presence of the proteosome inhibitor and by genistein.
      Alveolar macrophages showed adherence to immobilized sICAM-1 in a CD18-dependent
      manner. Finally, airway instillation of sICAM-1 intensified lung injury produced
      by intrapulmonary deposition of IgG immune complexes in a manner associated with
      enhanced lung production of TNF-alpha and MIP-2 and increased neutrophil
      recruitment. Therefore, through engagement of beta2 integrins, sICAM-1 enhances
      alveolar macrophage production of MIP-2 and TNF-alpha, the result of which is
      intensified lung injury after intrapulmonary disposition of immune complexes.

PMID- 9759894
TI  - Essential roles of Lyn in fibronectin-mediated filamentous actin assembly and
      cell motility in mast cells.
AB  - Although the requirement for c-Src in extracellular matrix (ECM)-mediated
      fibroblast motility has been well established, the roles of hemopoietic Src
      family protein tyrosine kinases in leukocyte migration have not been fully
      elucidated. To address the issue, we analyzed fibronectin (Fn)-mediated adhesion
      signaling in rat basophilic leukemia (RBL) 2H3 cells overexpressing 1) Csk, 2) a
      membrane-anchored, gain-of-function Csk (mCsk), and 3) a kinase-defective mCsk
      (mCsk(-)). Parent RBL2H3 cells, expressing autoactivated c-kit, readily adhered
      to Fn-coated surface, developed typical leukocyte adhesion machinery (podosome),
      and migrated toward Fn without cytokine priming, thus provided a simple
      experimental system to analyze Fn-mediated outside-in signaling. While
      overexpression of Csk or the Csk mutants did not significantly affect cell
      adhesion to the Fn surface or alpha5 integrin recruitment to the attachment
      sites, Csk suppressed and mCsk almost abolished Fn-mediated tyrosine
      phosphorylation of paxillin, filamentous actin assembly to podosomes, and cell
      migration, but mCsk(-) did not. Coexpression of LynA devoid of C-terminal
      negative regulatory tyrosine in mCsk cells successfully restored Fn-mediated
      podosome formation and cell migration. Coexpression of c-Src lacking the C
      terminal tyrosine reconstructed podosomes, but could not restore the cell
      migration regardless of its expression level. Collectively, these observations
      provide evidence that Src family protein tyrosine kinases are required, and that
      Lyn could transmit sufficient signal for Fn-mediated cytoskeletal changes leading
      to cell locomotion in RBL2H3 cells, and they suggest that Lyn and c-Src are
      differentially involved in cell motility.

PMID- 9759895
TI  - CXCR4 and CCR5 expression delineates targets for HIV-1 disruption of T cell
      differentiation.
AB  - HIV-1 disease is often associated with CD4+ T lymphopenia as well as quantitative
      reductions in naive CD8+ T cells and cytopenias involving nonlymphoid hemopoietic
      lineages. Studies in HIV-1-infected humans as well as in animal models of lenti
      virus disease indicate that these effects may be secondary to infection and
      destruction of multilineage and lineage-restricted hemopoietic progenitor cells.
      To define the stages of T cell differentiation that might be susceptible to HIV
      1, we performed flow cytometric analysis of the surface expression of CXCR4 and
      CCR5 on T cells and their progenitors from fetal tissue, cord blood, SCID-hu
      Thy/Liv mice, and adult peripheral blood. We found that CXCR4 is expressed at low
      levels on hemopoietic progenitors in the bone marrow, is highly expressed on
      immature (CD3-CD4+CD8-) T cell progenitors in the thymus, and then is down
      regulated during thymocyte differentiation. As thymocytes leave the thymus and
      enter the peripheral circulation, the expression of CXCR4 is again up-regulated.
      In contrast, CCR5 is undetectable on most hemopoietic progenitors in the bone
      marrow and on intrathymic T progenitor cells. It is up-regulated when thymocytes
      coexpress CD4 and CD8, then down-regulated either in the thymus (CD4+ cells) or
      during exit from the thymus (CD8+ cells). These results indicate that discrete,
      lineage-related populations of T cell progenitors may vary widely in their
      potential to respond to chemokines and to be infected by HIV-1, and that T
      lymphoid differentiation is particularly vulnerable to CXCR4-using viruses.

PMID- 9759896
TI  - Membrane cofactor protein: importance of N- and O-glycosylation for complement
      regulatory function.
AB  - Membrane cofactor protein (MCP; CD46) is a type 1 membrane glycoprotein that
      inhibits complement activation on host cells. It also is a measles virus (MV)
      receptor, an adherence factor for group A Streptococcus pyogenes, and a cellular
      pilus receptor for pathogenic Neisseria. The amino terminus of MCP consists of
      four complement control protein (CCP) repeats, three of which (CCP-1, -2, and -4)
      possess N-glycans. Immediately following the CCP modules is an alternatively
      spliced region for extensive O-glycosylation (termed the STP domain). Previous
      studies established that the N-glycan of CCP-2 is essential for MV binding and
      infection and that the splicing variants of the STP domain not only affect MV
      binding and fusion, but also differentially protect against complement-mediated
      cytolysis. In this report, we dissect the role of these carbohydrates on
      complement regulatory function. We constructed, expressed, and characterized
      proteins deleting these carbohydrates. For MCP-mediated protection against
      cytolysis, the N-glycans of CCP-2 and -4 were necessary, the STP segment
      influenced but was not essential, and the N-glycan of CCP-1 was not required. In
      addition, the rate and magnitude of cell surface cleavage of C4b to C4c and C4d
      by MCP and factor I correlated with cytoprotection. These studies expand the
      structure-function understanding of the active sites of MCP and elucidate an
      important role for carbohydrates in its function, a finding consistent with their
      conservation in the MCP of other species.

PMID- 9759897
TI  - A complex element regulates IFN-gamma-stimulated monocyte chemoattractant protein
      1 gene transcription.
AB  - Monocyte chemoattractant protein-1 (MCP-1) is induced in chronic osseous
      inflammation, and is temporally and spatially correlated with monocyte
      recruitment. We investigated the mechanism of MCP-1 regulation in a human
      osteoblastic cell line in response to IFN-gamma, a potent mediator of the immune
      inflammatory response. Nuclear run-on and stability studies demonstrated that IFN
      gamma stimulated MCP-1 transcription and did not enhance mRNA stabilization.
      Using MCP-1 promoter/reporter gene constructs, we determined that IFN-gamma
      enhanced MCP-1 transcription is regulated by a 29-bp element located at -227
      relative to the ATG start codon. This element contains a 13-bp CT-rich sequence
      (GCTTCCCTTTCCT) adjacent to a IFN-gamma activation site (GAS). Since deletion of
      the CT sequence enhanced both the magnitude and duration of IFN-gamma-stimulated,
      GAS-mediated transcription, we have termed it the IFN response-inhibitory
      sequence (IRIS). The combined IRIS/GAS sequence is highly conserved in mouse,
      rat, and bovine MCP-1 genes. In gel-shift assays, nuclear extracts from IFN-gamma
      stimulated osteoblastic cells formed two specific inducible bands with labeled
      IRIS/GAS DNA. Both bands were supershifted by anti-STAT1 Abs, but not by Abs to
      STAT2, p48(ISGF-3y), IFN-regulatory factor-1, or IFN-regulatory factor-2.
      Formation of one of the bands required the presence of the IRIS moiety. IRIS/GAS
      DNA also formed a number of specific complexes with constitutively expressed
      factors, none of which were affected by the above Abs. These studies establish a
      mechanism for IFN-gamma-stimulated MCP-1 expression and identify a complex
      element that regulates MCP-1 gene transcription.

PMID- 9759898
TI  - A RANTES-antibody fusion protein retains antigen specificity and chemokine
      function.
AB  - The successful eradication of cancer cells in the setting of minimal residual
      disease may require targeting of metastatic tumor deposits that evade the immune
      system. We combined the targeting flexibility and specificity of mAbs with the
      immune effector function of the chemokine RANTES to target established tumor
      deposits. We describe the construction of an Ab fusion molecule with variable
      domains directed against the tumor-associated Ag HER2/neu, linked to sequences
      encoding the chemokine RANTES (RANTES.her2.IgG3). RANTES is a potent
      chemoattractant of T cells, NK cells, monocytes, and dendritic cells, and
      expression of RANTES has been shown to enhance immune responses against tumors in
      murine models. RANTES.her2.IgG3 fusion protein bound specifically to HER2/neu Ag
      expressed on EL4 cells and on SKBR3 breast cancer cells as assayed by flow
      cytometry. RANTES.her2.IgG3 could elicit actin polymerization of THP-1 cells and
      transendothelial migration of primary T lymphocytes. RANTES.her2.IgG3 prebound to
      SKBR3 cells also facilitated migration of T cells. RANTES.her2.IgG3 bound
      specifically to the CCR5 chemokine receptor, as demonstrated by flow cytometry,
      and inhibited HIV-1 infection via the CCR5 coreceptor. RANTES.her2.IgG3, alone or
      in combination with other chemokine or cytokine fusion Abs, may be a suitable
      reagent for recruitment and activation of an expanded repertoire of effector
      cells to tumor deposits.

PMID- 9759899
TI  - Evidence for IL-12-activated Ca2+ and tyrosine signaling pathways in human
      neutrophils.
AB  - The cytokine IL-12 is proposed to play a bridging role between innate and
      adaptive immunity. Here we demonstrate that IL-12 binds specifically to human
      neutrophils. This binding leads to a transient increase in 1) intracellular free
      calcium due to its release from membrane-enclosed stores and its influx from
      extracellular medium, 2) actin polymerization, and 3) tyrosine phosphorylation.
      IL-12 treatment also leads to a concentration-dependent increase in reactive
      oxygen metabolite production. The effect of IL-12 is blocked by neutralizing Abs
      to IL-12. Inhibition of either calcium transient or tyrosine phosphorylation
      causes inhibition of reactive oxygen metabolite production. However, inhibition
      of actin polymerization enhances IL-12-induced oxidase activation. Our data
      suggest 1) a direct role for IL-12 in the activation of human neutrophils, and 2)
      a calcium-dependent signaling pathway for IL-12.

PMID- 9759900
TI  - Prostaglandin E2 stimulates IL-8 gene expression in human colonic epithelial
      cells by a posttranscriptional mechanism.
AB  - Intestinal mucosal epithelial cells produce IL-8, a neutrophil chemoattractant
      that contributes to mucosal inflammation in various infectious and inflammatory
      diseases. However, the mediators involved and the molecular regulation of IL-8
      production are poorly understood. As PGE2 is central in gut inflammation and
      modulates a variety of mucosal epithelial cell functions, we determined whether
      PGE2 can affect the expression of IL-8. Exogenous PGE2 induced the accumulation
      of IL-8 mRNA and protein production in a dose- and time-dependent manner in T84
      human colonic epithelial cells. Forskolin and dibutyryl cAMP, which increase
      intracellular cAMP, stimulated IL-8 in a fashion similar to that of PGE2. PGE2
      and PGE2 receptor agonists coupling through EP4 receptors elevated intracellular
      cAMP and up-regulated IL-8 mRNA expression by activating protein kinase A. Unlike
      PMA, PGE2 and forskolin did not increase IL-8 gene transcription. However, PGE2,
      forskolin, and PMA enhanced the stability of IL-8 mRNA transcripts, suggesting
      the involvement of posttranscriptional regulation. Chloramphenicol
      acetyltransferase reporter gene transfection studies confirmed the presence of a
      PGE2 responsive cis-element(s) in the IL-8 3' untranslated region. Furthermore,
      dexamethasone inhibited PGE2-, forskolin-, and dibutyryl cAMP-induced, but not
      PMA-induced, IL-8 protein production. These results highlight a novel role for
      PGE2 in up-regulating IL-8 gene expression by colonic epithelial cells, which may
      contribute to exacerbation of inflammation in the gastrointestinal tract.

PMID- 9759901
TI  - Poly(ADP-ribose) synthetase activation mediates mitochondrial injury during
      oxidant-induced cell death.
AB  - Reactive oxidant species are important mediators of tissue injury in shock,
      inflammation, and reperfusion injury. The actions of a number of these oxidants
      (e.g., hydroxyl radical and peroxynitrite, a reactive oxidant produced by the
      reaction of nitric oxide and superoxide) are mediated in part by the activation
      of the nuclear nick sensor enzyme, poly(ADP)-ribose synthetase (PARS), with
      consequent cellular energy depletion. Here we investigated whether PARS
      activation contributes to the mitochondrial alterations in cells exposed to
      oxidants. Authentic peroxynitrite (20 microM), the peroxynitrite-generating
      compound 3-morpholinosidnonimine, the combination of pyrogallol and S-nitroso-N
      acetyl-D,L-penicillamine, as well as hydrogen peroxide induced a time- and dose
      dependent decrease in mitochondrial transmembrane potential (delta psi(m)) in
      thymocytes, as determined by flow cytometry using the mitochondrial potential
      sensitive dyes DiOC6(3) and JC-1. A time- and dose-dependent increase in
      secondary reactive oxygen intermediate production and loss of cardiolipin, an
      indicator of mitochondrial membrane damage, were also observed, as measured by
      flow cytometry using the fluorescent dyes dihydroethidine and nonyl-acridine
      orange, respectively. Inhibition of PARS by 3-aminobenzamide or 5-iodo-6-amino
      1,2-benzopyrone attenuated peroxynitrite-induced delta psi(m) reduction,
      secondary reactive oxygen intermediate generation, cardiolipin degradation, and
      intracellular calcium mobilization. Furthermore, thymocytes from PARS-deficient
      animals were protected against the peroxynitrite- and hydrogen peroxide-induced
      functional and ultrastructural mitochondrial alterations. In conclusion,
      mitochondrial perturbations during oxidant-mediated cytotoxicity are, to a
      significant degree, related to PARS activation rather than to direct effects of
      the oxidants on the mitochondria.

PMID- 9759902
TI  - Genetic basis of human complement C8 alpha-gamma deficiency.
AB  - Deficiency of the alpha-gamma subunit of the eighth component of complement
      (C8alpha-gammaD) is frequently associated with recurrent neisserial infections,
      especially meningitis caused by Neisseria meningitidis. We here report the
      molecular basis of C8alpha-gammaD in two unrelated Japanese subjects. Screening
      all 11 exons of the C8alpha gene and all 7 exons of the C8gamma gene and their
      boundaries by exon-specific PCR/single-strand conformation polymorphism
      demonstrated aberrant single-stranded DNA fragments in exon 2 of C8alpha gene in
      case 1 and in exons 2 and 9 of C8alpha gene in case 2. Nucleotide sequencing of
      the amplified DNA fragments in case 1 revealed a homozygous single-point mutation
      at the second exon-intron boundary, inactivating the universally conserved 5'
      splice site consensus sequence of the second intron (IVS2+1G-->T). Case 2 was a
      compound heterozygote for the splice junction mutation, IVS2+1G-->T, and a
      nonsense mutation at Arg394 (R394X). R394X was caused by a C to T transition at
      nucleotide 1407, the first nucleotide of the codon CGA for Arg394, leading to a
      stop codon TGA. No mutations were detected in the C8gamma gene by our method. Our
      results indicate that the pathogenesis of C8alpha-gammaD might be caused by
      heterogeneous molecular defects in the C8alpha gene.

PMID- 9759903
TI  - Immune invasion of the central nervous system parenchyma and experimental
      allergic encephalomyelitis, but not leukocyte extravasation from blood, are
      prevented in macrophage-depleted mice.
AB  - Organ-specific autoimmune diseases are characterized by infiltrates, including T
      lymphocytes and activated macrophages. Macrophages and secondarily activated
      tissue resident counterparts can both present Ag to and contribute to cytokine
      secretion by T lymphocytes. We have previously shown a crucial role of peripheral
      macrophages in experimental allergic encephalomyelitis (EAE), a Th1-mediated
      demyelinating disease that serves as a an animal model for multiple sclerosis
      (MS), by their depletion using mannosylated liposome-encapsulated
      dichloromethylene diphosphonate (Cl2MDP). Here we describe studies to investigate
      the mechanisms by which macrophages contribute to the lesion formation in EAE, by
      studying the effect of Cl2MDP-containing mannosylated liposomes (Cl2MDP-mnL) on
      adoptively transferred EAE in SJL/J mice. Adoptive transfer of EAE with myelin
      basic protein-reactive CD4+ T cells to SJL/J mice was abrogated by Cl2MDP-mnL
      treatment. CD4+ T cell and MHC II+ B220+ B cell extravasation from blood vessels
      and Th1 cytokine production were not inhibited. However, invasion of the central
      nervous system intraparenchymal tissues by lymphocytes, F4/80+, Mac-1+, and MOMA
      1+ macrophages was almost completely blocked after treatment with Cl2MDP-mnL.
      Furthermore, in Cl2MDP-mnL-treated mice, the myelin sheaths appeared completely
      normal, whereas, in the control groups, marked demyelination occurred. Production
      of TNF-alpha and inducible nitric oxide synthase, both associated with
      macrophage/microglial activation, was inhibited. This intervention reveals a role
      for macrophages in regulating the invasion of autoreactive T cells and secondary
      glial recruitment that ordinarily lead to demyelinating pathology in EAE and
      multiple sclerosis.

PMID- 9759904
TI  - Role of kappa II-A2 light chain CDR-3 junctional residues in human antibody
      binding to the Haemophilus influenzae type b polysaccharide.
AB  - Abs using the kappaII-A2 V gene segment predominate the human Ab repertoire to
      the Haemophilus influenzae b (Hib) polysaccharide (PS). All A2 anti-Hib PS Abs
      sequenced to date possess a 10-amino acid L chain complementarity-determining
      region-3 (CDR-3) having an insertional arginine (Arg) at position 95a, the V-J
      junction. These findings suggest an essential requirement for this conserved Arg
      residue in determining Hib PS-binding affinity. We examined this requirement by
      performing chain recombination experiments in which a series of A2 L chains,
      differing at position 95a, were combined individually with an Fd region known to
      generate a Hib PS-combining site when paired with an A2-Arg(95a)-Jkappa1 V
      region. Hib PS binding of the recombinant Fabs was evaluated quantitatively using
      a radioantigen-binding assay. Fabs having A2 L chains with either Arg or lysine
      in position 95a in combination with Jkappa1 gave equivalent and strongest binding
      to Hib PS. Fabs having A2-Jkappa1 L chains with either tyrosine, glycine,
      alanine, leucine, serine, or threonine in position 95a, or having an A2-Arg(95a)
      Jkappa3 L chain, gave intermediate binding. Fabs having A2-Jkappa1 L chains with
      glutamate or aspartate at 95a or with no junctional residue showed little or no
      Hib PS binding. These results demonstrate the importance of L chain junctional
      residue, as well as Jkappa usage and CDR-3 length, in determining Hib PS-binding
      affinity. Contrary to expectation, an Arg junctional residue is not essential for
      generating either high or intermediate affinity-binding sites.

PMID- 9759905
TI  - Therapeutic preparations of normal polyspecific IgG (IVIg) induce apoptosis in
      human lymphocytes and monocytes: a novel mechanism of action of IVIg involving
      the Fas apoptotic pathway.
AB  - Therapeutic preparations of normal human IgG for i.v. use (i.v.Ig) exhibit a
      broad spectrum of immunoregulatory activities in vitro and in vivo. I.v.Ig has
      been shown to inhibit the proliferation of activated B and T lymphocytes and of
      several autonomously growing cell lines. In this study, we demonstrate that
      i.v.Ig induces apoptosis in leukemic cells of lymphocyte and monocyte lineage and
      in CD40-activated normal tonsillar B cells, involving, at least in part, Fas
      (CD95/APO-1) and activation of caspases. I.v.Ig-induced apoptosis was higher in
      Fas-sensitive HuT78 cells than in Fas-resistant HuT78.B1 mutant cells, and
      soluble Fas inhibited IVIg-induced apoptosis. I.v.Ig immunoprecipitated Fas from
      Fas-expressing transfectants and recognized purified Fas/glutathione-S
      transferase fusion proteins upon immunoblotting. Affinity-purified anti-Fas Abs
      from i.v.Ig induced apoptosis of CEM T cells at a 120-fold lower concentration
      than unfractionated i.v.Ig. Inhibitors of cysteine proteases of the caspase
      family, caspase 1 (IL-1beta-converting enzyme) and caspase 3 (Yama/CPP32b),
      partially inhibited i.v.Ig-induced apoptosis of CEM cells. Furthermore, cleavage
      of poly(A)DP-ribose polymerase into an 85-kDa signature death fragment was
      observed in CEM cells following i.v.Ig treatment. Thus, normal IgG induces
      apoptosis in lymphocytes and monocytes. Our results provide evidence for a role
      of Fas, bring new insights into the mechanisms of action of i.v.Ig in autoimmune
      diseases, and suggest a role of normal Ig in controlling cell death and
      proliferation.

PMID- 9759907
TI  - A case of congenital mumps infection complicated with persistent pulmonary
      hypertension.
AB  - A low-birth-weight female baby was admitted with respiratory distress after
      birth. Her mother had been diagnosed with mumps 4 weeks and 5 days prior to
      delivery. Mumps IgM antibody was elevated in the neonate and mumps virus
      ribonucleic acid was detected in the umbilical cord blood by reverse
      transcription-polymerase chain reaction. The perinatal virus infection was
      complicated with persistent pulmonary hypertension of the newborn and pulmonary
      hemorrhage. Successful treatment included the use of high frequency oscillation
      ventilation together with the administration of artificial surfactant.

PMID- 9759906
TI  - Prenatal ultrasonography: clinical and radiological findings in a boy with
      fibrochondrogenesis.
AB  - Fibrochondrogenesis, a rare lethal chondrodysplasia has been reported on nine
      patients. We report on a boy with fibrochondrogenesis whose parents were second
      cousins. Prenatal ultrasonography performed at 22 weeks of gestation revealed an
      intrauterine growth retardation, an apparently large head, an hypoplasia of the
      thorax, a prominent abdomen, rhizomelic limbs, and wide metaphysis. The latest
      have never been reported in other lethal dysplasias.

PMID- 9759908
TI  - Pregnancy performance and outcomes associated with diabetic nephropathy.
AB  - The purpose of the current study is to report the effect of diabetic nephropathy
      on pregnancy outcomes based on a review of the world's literature from 1981 to
      1996. In addition, the effects of pregnancy on renal function in a select
      subpopulation of patients is also presented. The Medline Computer System was used
      to survey the English language literature on diabetic nephropathy complicating
      pregnancy between 1981 and 1996, which yielded a total patient population of 315.
      The database was analyzed according to patient population, clinical management,
      maternal complications and outcomes, and fetal complications and outcomes. The
      frequency of chronic hypertension was 42% with 60% of women manifesting
      hypertension by the third trimester. Pre-eclampsia developed in 41% of patients;
      proliferative retinopathy was observed in 63% of patients prior to pregnancy, and
      cesarean section delivery was performed in 74% of the patients. Among the fetal
      outcomes, intrauterine growth restriction (IUGR) was observed in 15%, preterm
      delivery in 22%, and major congenital malformations in 8% of the patients
      included in the database. The observed overall perinatal morality rate was 5%.
      Gestational age at delivery was significantly correlated with first-trimester
      Cr/Cl (p < 0.01), third-trimester Cr/Cl (p < 0.05), third trimester proteinuria
      (p < 0.01), and third-trimester blood pressure (p < 0.001). Birth weight was
      significantly correlated with first-trimester Cr/Cl (p < 0.01), third-trimester
      Cr/Cl (p < 0.001), third-trimester proteinuria (p < 0.01), and third-trimester
      blood pressure (p < 0.001). Of the 185 patients available for long-term follow-up
      (mean 35 months), 17% developed end-stage renal disease, and 5% died as a result
      of renal insufficiency. Among the renovascular parameters, proteinuria and mean
      arterial pressure significantly increased from the first to the third trimester
      (p < 0.05). When these parameters were evaluated at follow-up, blood pressure did
      not show a significant increase from first trimester values, however, proteinuria
      did show a weak, but significant, increase postpartum. These data suggest that
      with contemporary methods of perinatal care, fetal survival rates of 95% are
      achievable in diabetic women with nephropathy. Furthermore, although many women
      experienced a temporary decline in renal function during gestation, pregnancy per
      se, does not appear to worsen the natural progression to end-stage renal disease
      for most women with renal insufficiency.

PMID- 9759909
TI  - Successful abdominal delivery in a woman with sonographic diagnosis of diffuse
      cavernous hemangioma of the uterus.
AB  - Diffuse hemangioma of the pregnant uterus is a serious lesion. We report the
      first case of a successful cesarean section at term following expectant
      management of pregnancy in a patient with presumed isolated diffuse cavernous
      hemangioma of the uterus and protein S deficiency. The sonographic diagnosis and
      clinical management of this condition is described. The presented successful
      pregnancy underlines that, under close surveillance, consideration should be
      given to a conservative approach to this sonographic finding during pregnancy, as
      even an abdominal delivery does not imply hysterectomy inevitably.

PMID- 9759910
TI  - Stem cell factor (SCF) levels in newborns.
AB  - We studied Stem cell factor (SCF) levels in 15 mother-newborn pairs, 15 healthy
      adult controls, and 16 newborn with bacterial sepsis. SCF levels were also
      determined in six newborns with sepsis before and after completion of treatment.
      SCF levels (pg/mL) were found to be 2141 +/- 529 in cord blood, 1385 +/- 314 in
      mothers, 1546 +/- 443 in healthy adult controls, and 1742 +/- 655 in septic
      newborns. Cord blood SCF levels were significantly higher than their mothers' and
      healthy controls (p < 0.05). There were no differences in SCF levels between
      mothers and healthy adult controls. No correlation was found between the SCF
      levels and absolute neutrophil counts. There were no differences in SCF levels
      between the before and after treatment levels in six newborn with sepsis. In
      conclusion, our study suggests that SCF levels were increased in cord blood, and
      this increase is not a reflection of mothers' levels. SCF levels do not show
      significant changes during sepsis in newborns.

PMID- 9759911
TI  - Antepartum fetal intracranial hemorrhage, predisposing factors and prenatal
      sonography: a review.
AB  - Our objective was to review current literature pertaining to antepartum fetal
      intracranial hemorrhage. To this goal we selected all manuscripts published in
      the English language regarding this topic obtained from a MEDLINE search for 1966
      through January 1998. Additional sources were identified through cross
      referencing. Antenatal fetal intracranial hemorrhage may occur spontaneously, or
      occur in association with various maternal or fetal conditions. Predisposing
      maternal conditions at risk for this occurrence include alloimmune and idiopathic
      thrombocytopenia, von Willebrand's disease, specific medications (warfarin) or
      illicit drug (cocaine) abuse, seizures, severe abdominal trauma inflicting
      subsequent fetal injury, amniocentesis, cholestasis of pregnancy and febrile
      disease. Predisposing fetal conditions include congenital factor-X and factor-V
      deficiencies, hemorrhage into various congenital tumors, twin-twin transfusion,
      demise of a co-twin, or fetomaternal hemorrhage. Currently, antepartum fetal
      intracranial hemorrhage may be diagnosed by imaging techniques including
      ultrasonography and less frequently, magnetic resonance imaging. Early real-time
      sonographic signs of intracranial hemorrhage consist of irregular echogenic
      patterns representing the associated hematoma that may clearly distort normal
      intracranial structures. Recent reports have suggested Doppler flow velocimetry
      and color Doppler imaging as additional tools in detecting fetal intracranial
      hemorrhage. Various types of antenatal fetal intracranial hemorrhages that have
      been visualized sonographically include intraventricular, periventricular,
      subependymal, parenchymal, subdural, and intracerebellar events. Active
      hemorrhages may be associated with fetal distress manifested by fetal heart rate
      changes. Infrequently, antenatal ultrasonographic depiction of intracranial
      hemorrhage may precede devastating sequelae such as hydrocephalus,
      hydranencephaly, porencephaly, or microcephaly. Due to the significant associated
      neonatal neurological impairment and potential medicolegal implications of
      antepartum fetal intracranial hemorrhage, it follows that obstetricians and
      sonographers should be familiar with predisposing factors and typical diagnostic
      imaging findings of these events.

PMID- 9759912
TI  - Lower thoracic spinal cord injury--a severe complication of shoulder dystocia.
AB  - Fundal pressure as a maneuver for the relief of shoulder dystocia is associated
      with up to a 77% fetal injury rate. The usual injuries involve the brachial
      plexus or orthopedic injuries. We now report a severe lower thoracic spinal cord
      injury with permanent neurological injury when fundal pressure was applied in an
      attempt to relieve shoulder dystocia. Shoulder dystocia occurred in a 28-year-old
      nulliparous woman. A series of manual maneuvers to include episiotomy extension,
      McRoberts, suprapubic pressure, Woods screw, and extraction of the posterior arm
      all failed to achieve delivery. During these maneuvers, but not coordinated with
      them, fundal pressure was applied by multiple individuals. The Zavanelli maneuver
      and cesarean delivery ultimately allowed delivery. On Day 2 of life marked
      decrease in lower extremity motor function, over-flow urinary incontinence, and
      rectal incontinence led to imaging studies that revealed focal spinal cord injury
      at T-9 through T-12. Compressive forces applied to the fetal spine during fundal
      pressure is the likely cause of the lower thoracic spinal cord injury manifest by
      this newborn.

PMID- 9759913
TI  - Right ventricular size is acutely decreased by inhaled nitric oxide in newborns
      with pulmonary hypertension.
AB  - The pressure and volume demands of the right and left ventricles may dramatically
      change following selective pulmonary vasodilation in newborns with pulmonary
      hypertension. Thus, ventricular planimetry was performed by two-dimensional
      echocardiography in 35 newborns with lung disease and increased pulmonary
      vascular resistance who were treated with inhaled nitric oxide to determine the
      influence of therapy on right and left ventricular size and function. The end
      diastolic and end-systolic areas of each ventricle were measured from apical 4
      chamber images before, and 30 to 60 minutes after, the onset of 20 parts per
      million inhaled nitric oxide. Estimates of ventricular function were determined
      by the systolic decrease in ventricular area, (diastolic area - systolic area) x
      100/diastolic area. Heart rate, systemic blood pressure, and left ventricular
      areas did not change. However, the oxygenation index, the proportion of right-to
      left ductal shunt (nonrestrictive ductus arteriosus, n = 22), the systolic
      pulmonary arterial pressure (closed or restrictive ductus arteriosus, n = 13),
      and the right ventricular diastolic and systolic areas were decreased after
      nitric oxide inhalation. The baseline systolic decrease in left ventricular area
      was lower in a subgroup of patients who developed an increase in left ventricular
      diastolic area following nitric oxide inhalation. Thus, nitric oxide improves
      pulmonary hemodynamics and decreases right ventricular size in newborns with lung
      disease and pulmonary hypertension. However, newborns may develop an increase in
      left ventricular size if left ventricular function is decreased prior to therapy.

PMID- 9759914
TI  - The computerized perinatal database: are the data reliable?
AB  - The purpose of this study is to examine the correctness of the clinical data from
      the computerized perinatal database (PC-Log) at a Mayo Health System hospital.
      This computerized database is used for electronic transmission of birth
      certificates in Wisconsin. The paper medical record is chosen for the comparison.
      Random selection of 99 charts from a total of 893 births at a tertiary perinatal
      center during 1995. Of 310 fields in the database, 32 variables were compared to
      a hand abstraction of the paper medical record. PC-Log had 100% positive
      predictive value (PPV) for eclampsia, prolonged rupture of membranes, pre
      existing diabetes, cesarean section, and transports. The sensitivity,
      specificity, and PPV for other variables (abortion, congenital anomalies,
      gestational diabetes, maternal hypertension, and maternal employment) showed
      moderate to high agreement, but was poor for maternal ethanol use during
      pregnancy. Compared to hand abstraction, PC-Log had no recorded cases of
      substance abuse, antenatal steroids, hyaline membrane disease, circumcision,
      maternal and infant length of stay. Means for birth weight 5 minute Apgar scores
      did not differ, and the correlations were r = 0.982 and r = 0.960. The PC-Log
      showed good agreement for many but not all the variables of clinical interest.

PMID- 9759915
TI  - ATP released by LPS increases nitric oxide production in raw 264.7 macrophage
      cell line via P2Z/P2X7 receptors.
AB  - P2Z/P2X7 receptor is a particular type of purinoceptor, which is selectively
      expressed on the surface of immune cells in neuronal and non-neuronal tissues.
      Despite intensive research on its involvement in the immune response, the exact
      mechanism whereby it affects intercellular signaling is far from clear yet. In
      this study, the effect of activation P2Z/P2X7 receptor was investigated on the
      bacterial lipopolysaccharide induced nitric oxide production in RAW 264.7
      macrophage call line using the nitrite/nitrate assay. The P2Z/P2X7 receptor
      agonist 3'-O-(4-benzoylbenzoyl)-adenosine 5'triphosphate increased concentration
      dependency the lipoplysaccharide (10 microg/ml) induced nitric oxide production
      between 10 microM and 250 microM. ATP also increased nitric oxide production in
      response to lipopolysaccharide, while ADP, 2-methylo-thio-adenosine 5'
      triphosphate and adenosine 5'triphosphate-gamma-S was without effect.
      Pretreatment with oxidized adenosine triphosphate, the selective P2Z/P2X7
      receptor antagonise (300 microM-1 microM) strongly decreased lipopolysaccaride
      induced nitric oxide production. Furthermore, on macrophages, pretreated with
      oxidized adenosine 5'-triphosphate (300 microM-1 mM), 3'-O-(4-benzoylbenzoyl)
      adenosine 5'-triphosphate and ATP did not affect lipopolysaccharide induced
      nitric oxide production. 15 min lipopolysaccharide treatment induced a transient
      and reversible release of endogenous ATP from RAW 264.7 cells, measured by the
      luciferin-luciferase assay. The effect of lipopolysaccharide to promote ATP
      release was concentration-dependent between 1-10 microg/ml. In summary, our
      results show that P2Z/P2X7 receptor activation results in an increase in nitric
      oxide production in response to lipopolysaccharide challenge. Since the P2Z/P2X7
      receptor antagonist oxidized adenosine triphosphate decreased lipopolysaccharide
      induced nitric oxide production, and lipopolysaccharide was able to promote ATP
      release from macrophage cells, it seems likely that endogenous ATP is involved in
      nitric oxide formation during endotoxin challenge.

PMID- 9759916
TI  - Effect of neonatal exposure to monosodium L-glutamate on regional GABA release
      during postnatal development.
AB  - Monosodium L-glutamate (MSG) causes neuronal lesions in certain brain regions
      when systemically given to young animals. Also, when glutamate (Glu) builds up in
      the intersynaptic space, it induces neuroexcitatory and neurocytotoxic effects,
      events mediated by several Glu receptors. Some of these receptors such as NMDA
      and AMPA receptors are present in the very earliest developmental stages of the
      central nervous system and play a major role in neuronal plasticity during
      synaptogenesis. In this paper, the GABAergic system vulnerability was determined
      in terms of [3H]-GABA release during postnatal development. [3H]-GABA release on
      days 14, 21, 30, and 60 days after birth was assessed for the cerebral cortex
      (CC), hippocampus (Hp) and striatum (S) in rats perinatally treated at days 1, 3,
      5, and 7 after birth with MSG. The results show a major decrease in baseline [3H]
      GABA release in the CC (30 and 60 days after birth) and the Hp (beginning day 21
      after birth) vs the control groups [intact rats and rats given a NaCl solution
      equimolar to that of MSG (eqNaCl)] while in the S baseline release remained
      unchanged. Stimulated [3H]-GABA release was decreased in the CC on days 14 and 21
      after birth and significantly increased on day 60 after birth vs the controls. In
      the Hp, a decrease was seen on days 14, 21, and 60 after birth vs the controls
      while stimulated [3H]-GABA release was decreased in the S vs the controls at all
      ages studied. No significant differences in stimulated [3H]-GABA release were
      found between the intact group and the group treated with eqNaCl on days 30 and
      60 after birth. Results show that CC, Hp and S GABAergic neurones are a major
      target for the effect of perinatally given MSG and suggest a possible decrease in
      the number of Hp GABAergic neurones while these results in CC and S suggest a
      modified neuronal plasticity. NMDA receptor and calcium involvement are discussed
      as significant mediators of these events.

PMID- 9759917
TI  - L-arginine uptake in rat cerebral mitochondria.
AB  - The kinetics of L-[14C]arginine (L-[14C]Arg) uptake and the effects of potential
      competitors on the uptake were analysed in nonsynaptic mitochondria isolated from
      rat cerebral hemispheres. Analysis of uptake kinetics revealed a high affinity
      component with a mean Km = 0.08 mM, and Vmax = 1.89 nmoles/min/mg, and a very low
      affinity component probably manifesting diffusion. The uptake of 25 mM L-Arg was
      strongly inhibited by a 20-fold excess of L-lysine (L-Lys) and L-ornithine (L
      Orn), but not by D-Arg nor any neutral amino acid, which resembles the
      characteristics of the gamma+ transport system operating in the nerve- and glia
      cell-, and synaptic plasma membranes. Also in consistance with the other gamma+
      systems, L-Arg uptake to mitochondria was inhibited by a nitric oxide synthase
      (NOS) inhibitor L-N-monomethyl arginine (L-NMMA), but not by another NOS
      inhibitor NG-nitro-L-arginine (L-NNA). However, the uptake was very little
      affected by 20-fold excess of L-histidine (L-His), L-glutamate (L-Glu) or L
      glutamine (L-Gln), which is in contrast to the nonmitochondrial systems. The
      uptake was only marginally influenced by cytoplasmic L-Arg metabolites: ammonia,
      creatine, putrescine, or the mitochondrial L-Arg decarboxylation product,
      agmatine.

PMID- 9759918
TI  - Metallothionein-I+II induction by zinc and copper in primary cultures of rat
      microglia.
AB  - Metallothioneins (MTs) are a family of low molecular weight proteins which in
      rodents comprise four isoforms (MT-I to -IV). MT-I+II are widely expressed
      isoforms which are highly inducible by factors such as heavy metals and a number
      of hormones. The expression of these isoforms in the brain has been regarded as
      basically astrocytic, and to a lower extent, neuronal. We, however, demonstrate
      in this report, by radioimmunoassay and immunocytochemistry, that MT-I+II are
      expressed in primary cultures of rat microglia and that, furthermore, they are
      inducible by zinc and copper. Thus all major brain cell types may express the MT
      I+II isoforms and respond with increased protein levels to physiological stimuli
      such as increased extracellular zinc and copper content. In contrast, microglia
      MT-I+II levels are not affected by either the glucocorticoid dexamethasone or the
      cytokine IL-1 under the experimental conditions.

PMID- 9759919
TI  - Heparin modulates adenine nucleotide hydrolysis by synaptosomes from cerebral
      cortex.
AB  - The modulatory effect of heparin and dextran sulfate 500,000 (sulfated
      polysaccharides) was studied on ATPDase and 5'-nucleotidase activities. These
      enzymes participate in the degradation of ATP and adenosine production at the
      synaptic cleft level. Nucleotide hydrolysis was inhibited by heparin and dextran
      sulfate 500,000. For ADP, the inhibition was more evident at low cation
      concentrations (0.15 mM Ca2+ or Mg2+), reaching a maximum of 75%. For ATP, the
      inhibitory effect was less prominent and independent of divalent cation
      concentration, reaching a maximum of 25%. For AMP, the inhibition observed was
      similar with either relatively high (1 mM) or with low Mg2+ concentrations tested
      (0.1 mM) and reached a maximum of 35%. K+ did not change the inhibitory potency
      of sulfated polysaccharide suggesting that its effects were not exclusively
      related to charge interaction. These results suggest that heparin and possibly
      other naturally occurring sulfated polysaccharides may have a potential role as
      modulator of extracellular nucleotide hydrolysis in the synaptic cleft region.

PMID- 9759920
TI  - Enhancement of serotonin transporter function by tumor necrosis factor alpha but
      not by interleukin-6.
AB  - Serotonin (5-HT) is a prime candidate for studies of the interaction between the
      nervous and immune systems, since it is both an important neurotransmitter and
      released at high concentrations at sites of inflammation. Serotonergic
      neurotransmission is regulated by the 5-HT transporter (5-HTT), which determines
      the magnitude and duration of serotonergic responses. Since tumor necrosis factor
      alpha (TNF-alpha) and interleukin-6 are two inflammatory mediators that are
      central to the initiation of inflammation, we studied the impact of these
      cytokines on the 5-HTT. As model system we used a cell line which constitutively
      expresses the 5-HTT, namely the choriocarcinoma cell line JAR. We found that TNF
      alpha enhances 5-HT uptake, with a doubling of the maximal velocity of uptake.
      Interleukin-6, on the other hand, had no effect. We thus show for the first time
      that the cytokine TNF-alpha modulates 5-HTT function. Furthermore, we propose a
      molecular mechanism for this effect. Since both 5-HT and TNF-alpha are elevated
      at sites of inflammation, TNF-alpha may act to renormalize 5-HT levels by way of
      its effect on the 5-HTT. This is especially important for the central nervous
      system, where the TNF-alpha effect shown here can aid in preventing disturbances
      of serotonergic neurotransmission.

PMID- 9759921
TI  - The role of nitric oxide in striatal acetylcholine release induced by N-methyl-D
      aspartate.
AB  - Effect of nitric oxide (NO) on striatal acetylcholine (ACh) release induced by N
      methyl-D-aspartate (NMDA) was investigated in freely moving rats by means of
      microdialysis. NMDA caused a significant increase in ACh release in the striatum,
      which was blocked by the specific NMDA receptor antagonists, (+/-)-3-(2
      carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and (+)-5-methyl-10,11
      dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801),
      indicating that agonist-evoked increase in ACh release in the striatum was
      through an NMDA receptor-mediated mechanism. NG-monomethyl-L-arginine acetate
      salt (L-NMMA; a NO synthase inhibitor) facilitated NMDA-evoked increase in ACh
      release, while L-arginine (the precursor of NO) inhibited the ACh release. The
      increase by L-NMMA of ACh release induced by the NMDA was also blocked by L
      arginine. These results suggest that NO induced by NMDA receptor-mediated
      mechanism in cholinergic neurons may mediate an inhibitory regulation of ACh
      release.

PMID- 9759922
TI  - Calcium influx via ionotropic glutamate receptors causes long lasting inhibition
      of metabotropic glutamate receptor-coupled phosphoinositide hydrolysis.
AB  - Functional interaction between ionotropic and metabotropic glutamate receptors
      (iGluR and mGluR respectively) was studied in cerebellar granule cell cultures
      using quisqualate (QA), the most potent agonist of phosphoinositide hydrolysis
      coupled mGluR, and N-methyl-D-aspartate (NMDA) or kainate (KA) that activate
      different classes of iGluR. Two h exposure to NMDA or KA resulted in a marked
      reduction (about 75%) of QA-evoked PI hydrolysis. The efficacy of the two
      agonists was about the same, but the potencies were different (IC50 for NMDA
      about 35 microM and for KA about 70 microM). NMDA-induced depression of QA
      stimulated PI hydrolysis was relatively long lasting but reversible. Recovery
      required protein synthesis. In nominally Ca2+-free medium both NMDA and KA failed
      to attenuate QA-stimulated PI hydrolysis. The effect of NMDA was prevented by the
      NMDA receptor antagonist MK801, but not by the wide spectrum protein kinase
      inhibitor staurosporin nor by the nitric oxide synthase inhibitor N omega-nitro-L
      arginine. Cycloheximide and concanavalin A were also ineffective. The effect of
      KA was prevented by the selective non-NMDA receptor antagonist 2,3-dihydroxy-6
      nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX). Voltage sensitive Ca2+ channel
      antagonists together with MK801 did not counteract the inhibition by KA of the QA
      response. Both NMDA and KA attenuated PI hydrolysis evoked by the muscarinic
      receptor agonist carbachol (about 30%), indicating that the activation of iGluRs
      exerts a relatively general inhibitory effect on the function of different PLC
      coupled metabotropic receptors. Consistent with this observation is that
      treatments either with KA and NMDA induced an inhibition (about 30%) of NaF
      stimulated PI hydrolysis which occurs through the direct activation of G
      proteins. Our observations show that ionotropic glutamate receptor stimulation
      induces a long lasting suppression of QA-evoked PI breakdown through a Ca2+
      dependent mechanism which seems to involve receptor coupled transduction systems
      downstream from mGluR. Such a Ca2+-dependent cross-talk involving ionotropic and
      metabotropic receptors may play a role in certain events of synaptic plasticity.

PMID- 9759923
TI  - Quantification of human dopamine D2s receptor interactions with G alpha(i,1,2)-
      and G alpha(o)-proteins.
AB  - A simple and rapid in vitro method for qualitative and quantitative estimation of
      the G alpha-subunits interaction with the third intracellular loop of human D2s
      dopamine receptor has been developed. For this purpose, D2s-CL3 was cloned in
      pGEX-2T vector and expressed in E. coli BL21 DE3 as a fusion protein with
      glutathione-S-transferase (D2s-CL3-GST). The resulting soluble construct was
      purified by affinity chromatography on glutathione-Sepharose. G alpha-subunits
      were expressed and purified as His-tagged proteins. For the assay of G alpha/D2s
      CL3-GST interactions, varying concentrations of pure His-tagged G alpha-proteins
      were immobilized on His-Bind Resin and titrated with D2s-CL3-GST fusion protein.
      G alpha/D2s-CL3-GST interactions were quantified by GST activity determination
      assay. It was shown that the fusion protein interacts specifically with different
      G alpha proteins, especially with G alpha(i) proteins. Based on saturation
      binding analyses, Kd values were determined revealing the highest affinity of His
      G alpha(i,2) binding to the fusion protein. The affinities for G alpha(i)/D2s-CL3
      GST protein interactions estimated in this way were in nanomolar range of
      concentrations.

PMID- 9759924
TI  - Elevation of cerebral proteases after systemic administration of aluminum.
AB  - The levels of three proteases in the cerebral cortex of rats following a three
      week exposure to aluminum, were measured. The activity of apopain (CPP32), an
      interleukin 1beta converting enzyme (ICE)-like cysteine protease specifically
      associated with apoptosis, was increased following dosing with aluminum. The
      activity of calcium-activated neutral protease, calpain, was also increased.
      However, the enzyme activity of trypsin-like serine protease, known to be
      elevated by oxidative events, was unchanged. Since aluminum is suspected as a
      possible factor in the pathogenesis of Alzheimer's disease and other neurological
      diseases, it is speculated that changed levels in proteolytic enzymes may relate
      to the neurotoxicity of aluminum.

PMID- 9759925
TI  - Liver-directed gene transfer vectors.
AB  - The ultimate goal of liver-directed gene therapy for genetic diseases is the
      stable expression of a therapeutic transgene in a significant proportion of
      hepatocytes. This article considers the various liver-directed gene transfer
      procedures studied so far. Performances and limitations of currently available
      vector systems are discussed with respect to their clinical relevance. Although
      some improvements have been reported, naked DNA and nonviral gene transfer
      vectors induce transient expression in only a limited number of cells. Clinical
      applications of retrovirus-mediated gene transfer are hampered by the need to
      induce hepatocyte division. First-generation adenovirus vectors are highly
      efficient; however, they induce an immune response leading to the rapid rejection
      of transduced cells. Promising new vector systems have emerged, including gutless
      adenovirus vectors, adeno-associated vectors, and lentivirus vectors. However,
      these systems are still poorly documented and their relevance to liver-directed
      gene therapy must be confirmed.

PMID- 9759926
TI  - Apoptosis by retrovirus- and adenovirus-mediated gene transfer of Fas ligand to
      glioma cells: implications for gene therapy.
AB  - Astrocytic tumors frequently express Fas/APO-1 (Fas), in sharp contrast to
      surrounding normal brain cells, providing a potential window through which
      selective killing of tumor cells could be pursued. To assess this possibility, we
      transduced Fas into U251, a glioma cell line resistant to anti-Fas antibody
      mediated apoptosis, and obtained transfectants with high levels of Fas
      expression. Anti-Fas antibody showed significantly enhanced cytotoxicity for the
      transfectants, suggesting that U251 cells maintained an intercellular cascade of
      Fas-mediated apoptosis. When U251 transfectants with high-level Fas expression
      were transduced with Fas ligand-encoding gene via retrovirus, they were
      unaffected by exposure to anti-Fas antibody or Fas ligand adenovirus (Adeno-FL).
      Thus, retroviral induction of Fas ligand into the glioma cells with high levels
      of Fas led to the selection of cells that were resistant to Fas-dependent
      apoptosis. These resistant U251 transfectants were susceptible to FADD adenovirus
      (Adeno-FADD)-induced apoptosis, indicating that a cascade of death signals was
      blocked at the steps between Fas ligand and FADD. As for adenoviral transduction
      of Fas ligand into gliomas, gliomas with a relatively high level of expression of
      Fas were remarkably sensitive to Adeno-FL-induced apoptosis. Besides, Adeno-FADD
      induced pronounced apoptosis in all glioma cells. Our data suggest the
      possibility of using adenovirus-mediated transduction of Fas ligand and FADD
      genes as a therapeutic approach to target gliomas.

PMID- 9759927
TI  - Use of nonautologous microencapsulated fibroblasts in growth hormone gene therapy
      to improve growth of midget swine.
AB  - The aim of the present study was to investigate the expression activity, both in
      vitro and in vivo, of the porcine growth hormone complementary DNA (pGH cDNA) in
      porcine fetal fibroblast (PFF) cells. The pGH gene had been constructed inside
      the bicistronic retroviral vector PSN and subsequently transfected into PFF cells
      further encapsulated with immunoprotective microcapsules. This would provide a
      way to evaluate the improvement in growth performance of Tao-Yuan swine by the
      use of nonautologous microencapsulated fibroblasts carrying the pGH cDNA via the
      technique of somatic gene therapy. Results from Southern blot analysis confirmed
      that the full length of the pGH cDNA was completely integrated into the genome of
      the PFF cells after they had been infected one to four times using a PSN
      retroviral vector. Moreover, Northern blot analysis showed that high
      transcription activity was present in clones infected twice, and exogenous pGH
      secretion was found when the pGH-infected PFF had been further cultured for 48 hr
      in vitro and subjected to immunoblot assay. Encapsulation of the pGH-PFF with an
      alginate-poly-L-lysine-alginate membrane did not show any deterioration in their
      proliferation and survival both in vitro and in vivo. The pGH gene in
      encapsulated recombinant fibroblasts was fully expressed after it had been
      transplanted into the peritoneal cavity of the Tao-Yuan swine, and reverse
      transcription-polymerase chain reaction (RT-PCR) analysis was performed on the
      microcapsules retrieved 1 month later. The feasibility of pGH gene therapy to
      improve midget Tao-Yuan swine growth enhancement is further supported by the fact
      that transplantation of the encapsulated recombinant fibroblast cells resulted in
      a much more significant increase in weight gain than in those swine in either the
      age-matched untreated control group or in those that had been transplanted with
      uncapsulated recombinant PFF cells (10.56 +/- 1.01 kg versus 6.95 +/- 0.94 and
      5.27 +/- 1.30 kg; p < 0.05). These experimental data suggest that growth hormone
      gene therapy did provide an alternative approach for growth improvement in midget
      Tao-Yuan swine.

PMID- 9759928
TI  - Anti-HIV type 1 activity of wild-type and functional defective RANTES intrakine
      in primary human lymphocytes.
AB  - We have developed a genetic "intrakine" strategy to inactivate the CC-chemokine
      receptor 5 (CCR-5), the principal coreceptor for macrophage (M)-tropic HIV-1
      viruses (Yang et al, 1997). The inactivation of CCR5 was achieved by targeting a
      modified CC-chemokine (RANTES) to the lumen of the endoplasmic reticulum (ER) to
      block the transport of the newly synthesized CCR-5. The transduced lymphocytes
      with the phenotypic CCR5 knockout were shown to be resistant to M-tropic HIV-1
      infection. This study illustrated the feasibility of the intrakine strategy to
      block HIV-1 infection. In our current study, the potential clinical application
      of the intrakine approach was further evaluated in human peripheral blood
      lymphocytes (PBLs). PBLs were transduced with the RANTES intrakine gene by using
      retroviral vectors with the truncated low-affinity human nerve growth factor
      receptor (deltaNGFR) marker, and then isolated by an anti-NGFR antibody/magnetic
      bead method. The surface expression of CCR-5 in the transduced lymphocytes was
      dramatically inhibited, as demonstrated by flow cytometric assays. The transduced
      PBLs were shown to resist various types of M-tropic HIV-1 virus infection. The
      cell viability, cell proliferation rates, and cell surface markers of the
      intrakine-transduced PBLs were shown to be comparable to those of control PBLs.
      The transduced PBLs were also found to respond to the stimulation of various CXC-
      and CC-chemokines, other than RANTES. The transduced PBLs responded to tetanus
      antigen stimulation by increasing IL-2 production and cell proliferation. In
      addition, a functionally defective mutant of RANTES that retains its binding
      activity to CCR-5, but loses its signaling ability, was used to generate a mutant
      RANTES intrakine. The primary lymphocytes transduced with the mutant RANTES
      intrakine were found to be resistant to M-tropic HIV-1 infection. From these
      results, we conclude that the primary human lymphocytes transduced with either
      the wild-type or functionally defective RANTES intrakine are resistant to M
      tropic HIV-1 infection, and maintain their basic biological functions. This
      study, therefore, indicates the potential clinical application of the intrakine
      approach for HIV-1 gene therapy.

PMID- 9759929
TI  - Ganciclovir chemoablation of herpes thymidine kinase suicide gene-modified tumors
      produces tumor necrosis and induces systemic immune responses.
AB  - The goal of this work was to identify potential host immune responses to
      thymidine kinase (TK) suicide gene-modified tumors undergoing chemoablation
      induced by the prodrug ganciclovir (GCV). The aims were to measure the efficacy
      and specificity of immunity induced against unmodified tumor, to identify
      qualitative or quantitative changes in the host response to TK+ tumors undergoing
      chemoablation that may contribute to the induction of antitumor immunity, and to
      compare critically the induction of immunity by chemoablation of TK-modified
      tumors with that of other methods of immunization in this tumor model and in
      response to other well-defined model antigens. Animals treated with TK+ tumors
      and GCV developed specific resistance to rechallenge with unmodified tumor. GCV
      induced significant tumor necrosis, which was associated with a pronounced host
      cell infiltrate composed of polymorphonuclear cells, both CD4+ and CD8+ T
      lymphocytes, and increased intratumoral IL-12. Cyclophosphamide-treated mice
      exhibited no such host response despite the induction of tumor necrosis. CTL
      responses to defined antigens in TK+ cells were greater in animals treated with
      prodrug than were those in animals not treated with prodrug but harboring live
      TK+ cells. Similar degrees of immunity were produced by immunization with
      irradiated cells.

PMID- 9759930
TI  - Locoregional response and increased natural killer activity after intratumoral
      injection of HLA-B7/beta2-microglobulin gene in patients with cancer.
AB  - The purpose of this study was to assess the therapeutic potential of injecting
      the gene for HLA-B7/beta2-microglobulin into the subcutaneous metastatic nodules
      of patients who are refractory to conventional treatments. The nine patients
      evaluated were divided into three groups and given escalating doses of DNA (20,
      40, and 100 microg of the HLA-B7 plasmid DNA/lipid complex for each group) every
      2 weeks. Biopsy specimens from the treated tumor nodules of all nine patients
      were positive for the presence of DNA and for HLA-B7 mRNA expression. Moreover,
      in six of the nine patients, immunohistology of tumor biopsy samples revealed the
      expression of recombinant HLA-B7 protein. Also, all nine patients showed an
      increase in NK activity in their circulating peripheral blood lymphocytes. In two
      lung cancer patients, one partial and one mixed response was observed after gene
      transfer. These responses were confined to the treated nodules and the untreated
      locoregional lymph nodes; the lung masses showed no regression. Remission
      durations were 14 and 6 weeks, respectively, and in a total of 35 cycles no
      significant toxicities were observed. Immunohistologic analysis revealed an
      increased infiltration of CD4+ T cells, macrophages, and NK cells after therapy.
      In two responding cases, direct intratumoral injection of an allogeneic class I
      gene could elicit an antitumor response in locoregional areas, possibly through
      the activation of NK cells.

PMID- 9759931
TI  - Reinnervation of motor endplates and increased muscle fiber size after human
      insulin-like growth factor I gene transfer into the paralyzed larynx.
AB  - Current surgical strategies for the treatment of laryngeal paralysis are limited
      by the muscle atrophy associated with denervation. Moreover, attempts at
      reinnervation have not effected significant change in surgical outcome. To
      address this clinical problem, we have developed a rat laryngeal paralysis model
      to study novel gene transfer strategies. Using this model, the human insulin-like
      growth factor I (hIGF-I) gene was introduced into paralyzed rat laryngeal muscle
      to assess the benefit of sustained local hIGF-I production. A muscle-specific
      nonviral vector containing the alpha-actin promoter and hIGF-I gene was used in
      formulation with a polyvinyl-based delivery system and injected into paralyzed
      adult rat laryngeal muscle. Twenty-eight days after a single injection, gene
      transfer efficiency, muscle fiber size, motor endplate length, and nerve-to-motor
      endplate contact were evaluated. Gene transfer was detected in 100% of injected
      animals by PCR. Gene transfer with expression, as measured by RT-PCR for hIGF-I
      mRNA, occurred in 81.3 % of injected animals. When compared with controls, hIGF-I
      transfected animals presented a significant increase in muscle fiber diameter
      [17.56 (+/-0.97 SD) microm versus 14.70 (+/-1.43 SD) microm; p = 0.0002], a
      significant decrease in motor endplate length [20.88 (+/-1.42 SD) microm versus
      25.41 (+/-3.19 SD) microm; p = 0.0025], and a significant increase in percentage
      of endplates with nerve contact (20.3% (+/-13.9 SD) versus 4.4% (+/-4.2 SD); p =
      0.0079). In the context of laryngeal paralysis, gene therapy represents a
      tremendous opportunity to augment current surgical treatment modalities by
      preventing or reversing muscle atrophy, and by enhancing nerve sprouting and
      reinnervation.

PMID- 9759932
TI  - Immune response to Philadelphia chromosome-positive acute lymphoblastic leukemia
      induced by expression of CD80, interleukin 2, and granulocyte-macrophage colony
      stimulating factor.
AB  - We examined the potential of generating an immune response against Philadelphia
      chromosome-positive acute lymphoblastic leukemia. The immunostimulatory molecules
      chosen for this study were the cytokines IL-2 and GM-CSF and the costimulatory
      ligand CD80 (B7.1). We used a murine model based on a BALB/c pre-B cell line,
      BM185wt, in which leukemia is induced by the p185 BCR-ABL oncogenic product,
      which reproduces Philadelphia chromosome-positive ALL. BM185wt cells were
      transduced with retroviral vectors and the transduced clones expressing mIL-2,
      mGM-CSF, or mCD80 were used for challenge. Expression of the immunomodulators by
      BM185 cells was correlated with delay in leukemia development in immunocompetent
      mice, but not in immunodeficient mice, indicating an immune response against the
      modified leukemia cells. Expression of CD80 caused leukemia rejection in 50% of
      the cohort, which was associated with the CD4+ and CD8+ T cell-dependent
      development of anti-leukemia cytotoxic T lymphocytes. Furthermore, mice surviving
      the BM185/CD80 challenge or preimmunized with irradiated BM185/CD80 cells
      developed an immune response against subsequent challenge with the parental
      leukemia. These studies provide evidence that immunotherapeutic approaches can be
      developed for the treatment of ALL.

PMID- 9759933
TI  - Antitumor activity of bax and p53 naked gene transfer in lung cancer: in vitro
      and in vivo analysis.
AB  - In vitro and in vivo data have demonstrated that virus-mediated p53 gene transfer
      can induce active cell death and lung tumor regression. In contrast, the
      therapeutic potential of bax, another apoptosis-inducing gene, has not been
      described. We compared p53 and bax cytotoxic effects by transient transfection of
      an average of 25 +/- 5% of the H-322 and H-358 bronchioloalveolar carcinoma cell
      lines in vitro. Under these conditions, bax expression killed 70 to 90% of the
      transfected cells whereas p53 killed only 40% of them. The killing activity of
      both genes involved apoptosis, as shown by TUNEL staining. Surprisingly, BrdU
      incorporation indicated that the cells that did resist Bax toxicity were blocked
      in the pre-S phase of the cell cycle, a result expected for p53 only. In vivo,
      repeated injections of naked DNA encoding Bax or p53 inhibited the growth of 4-mm
      preestablished H-322 tumors in nude mice. Growth retardation only, and not
      inhibition, was observed in H-358, a poorly transfectable and rapidly growing
      tumor. These results indicate that Bax and p53 share a similar, strong antitumor
      activity in vivo, even if the former is a more potent inducer of apoptosis in
      vitro.

PMID- 9759935
TI  - Biodistribution and gene expression of lipid/plasmid complexes after systemic
      administration.
AB  - The objectives of this study were to investigate the influence of physicochemical
      properties of lipid/plasmid complexes on in vivo gene transfer and
      biodistribution characteristics. Formulations based on 1,2-di-O-octadecenyl-3
      trimethylammonium propane (DOTMA) and novel biodegradable cationic lipids, such
      as ethyl dioleoyl phosphatidylcholine (EDOPC), ethyl palmitoyl myristyl
      phosphatidylcholine (EPMPC), myristyl myristoyl carnitine ester (MMCE), and oleyl
      oleoyl L-carnitine ester (DOLCE), were assessed for gene expression after tail
      vein injection of lipid/plasmid complexes in mice. Gene expression was influenced
      by cationic lipid structure, cationic lipid-to-colipid molar ratios, plasmid-to
      lipid charge ratios, and precondensation liposome size. Detectable levels of
      human growth hormone (hGH) in serum, human factor IX (hFIX) in plasma, and
      chloramphenicol acetyltransferase (CAT) in the lung and liver were observed with
      positively charged lipid/plasmid complexes prepared from 400-nm extruded
      liposomes with a cationic lipid-to-colipid ratio of 4:1 (mol/mol). Intravenous
      administration of lipid/CAT plasmid complexes resulted in distribution of plasmid
      DNA mainly to the lung at 15 min after injection. Plasmid DNA accumulation in the
      liver increased with time up to 24 hr postinjection. There was a 10-fold decrease
      in the amount of plasmid DNA in the lung at 15 min after injection, when the
      lipid/plasmid complex charge ratio was decreased from 3:1 to 0.5:1 (+/-). Bright
      fluorescent aggregates were evident in in vivo-transfected lung with the
      positively charged pCMV-CAT/DOLCE:dioleyl phosphatidylethanolamine (DOPE) (1:1,
      mol/mol) complexes, while more discrete punctate fluorescence was observed with a
      4:1 molar ratio of cationic lipid:colipid formulations. Preinjection of
      polyanions such as plasmid, dextran sulfate, polycytidic acid, and polyinosinic
      acid decreased hGH expression, whereas the preinjection of both positively
      charged and neutral liposomes had no effect on hGH serum levels. Of the cationic
      lipids tested, DOLCE was found to be the most effective potentially biodegradable
      cationic lipid. A correlation between gene expression and cationic lipid:colipid
      ratios and lipid-to-plasmid charge ratio was also observed for DOTMA- and DOLCE
      based formulations.

PMID- 9759934
TI  - A phase I study of adenovirus-mediated wild-type p53 gene transfer in patients
      with advanced non-small cell lung cancer.
AB  - Mutations of the tumor suppressor gene p53 are the most common genetic
      alterations observed in human cancer. Loss of wild-type p53 function impairs cell
      cycle arrest as well as repair mechanisms involved in response to DNA damage.
      Further, apoptotic pathways as induced by radio- or chemotherapy are also
      abrogated. Gene transfer of wild-type p53 was shown to reverse these deficiencies
      and to induce apoptosis in vitro and in preclinical in vivo tumor models. A phase
      I dose escalation study of a single intratumoral injection of a replication
      defective adenoviral expression vector encoding wild-type p53 was carried out in
      patients with incurable non-small cell lung cancer. All patients enrolled had p53
      protein overexpression as a marker of mutant p53 status in pretreatment tumor
      biopsies. Treatment was performed either by bronchoscopic intratumoral injection
      or by CT-guided percutaneous intratumoral injection of the vector solution.
      Fifteen patients were enrolled in two centers, and were treated at four different
      dose levels ranging from 10(7) to 10(10) PFU (7.5 x 10(9) to 7.5 x 10(12)
      particles). No clinically significant toxicity was observed. Successful transfer
      of wild-type p53 was achieved only with higher vector doses. Vector-specific wild
      type p53 RNA sequences could be demonstrated in posttreatment biopsies of six
      patients. Transient local disease control by a single intratumoral injection of
      the vector solution was observed in four of those six successfully transduced
      patients. There was no evidence of clinical responses at untreated tumor sites.
      Wild-type p53 gene therapy by intratumoral injection of a replication-defective
      adenoviral expression vector is safe, feasible, and biologically effective in
      patients with advanced non-small cell lung cancer.

PMID- 9759937
TI  - Transduced fibroblasts and metachromatic leukodystrophy lymphocytes transfer
      arylsulfatase A to myelinating glia and deficient cells in vitro.
AB  - Metachromatic leukodystrophy (MLD) is a lysosomal storage disease, caused by
      deficiency of arylsulfatase A (ASA), that manifests primarily in the white matter
      of the nervous system. Currently, no specific treatment exists that will reverse
      its fatal outcome. Replacement therapy has been hampered by the blood-brain
      barrier (BBB). To circumvent this problem we designed an ex vivo gene therapy
      strategy that includes the retrovirus-mediated ASA transduction of cells, such as
      activated lymphocytes, that are able to traverse the BBB or other membranes of
      the CNS. For this purpose, two recombinant retroviruses based on the pLXSN vector
      were produced, containing the wild-type ASA cDNA or a pseudodeficiency ASA cDNA,
      which encodes a smaller enzyme with normal activity. After transduction, ASA
      activity increased more than 100-fold in fibroblasts from an MLD patient.
      Furthermore, ASA-transduced MLD PBLs expressed 30 times higher ASA activity when
      compared with control PBLs. Moreover, cell culture experiments demonstrated that
      transduced fibroblasts could efficiently transfer ASA to deficient cells across a
      transwell barrier, whereas transduced MLD lymphocytes could transfer ASA to
      deficient fibroblasts only by direct cell-to-cell contact. Finally, ASA was taken
      up by normal oligodendrocytes and Schwann cells, the target myelinating glial
      cells for therapy in MLD. These data suggest possible short-term strategies for
      transfer of ASA into the CNS via transduced autologous cells while long-term
      strategies, related to autologous transduced bone marrow transplant, take effect
      in patients.

PMID- 9759936
TI  - Adenovirus-mediated granulocyte-macrophage colony-stimulating factor improves
      lung pathology of pulmonary alveolar proteinosis in granulocyte-macrophage colony
      stimulating factor-deficient mice.
AB  - Mutation of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene by
      homologous recombination causes progressive pulmonary alveolar proteinosis (PAP)
      in GM-CSF-deficient mice (GM-/-). The present study tested whether adenovirus
      mediated expression of GM-CSF alters the progression of PAP in GM-/- mice. Adult
      mice were pretreated with an anti-T cell receptor (TCR) antibody to block T cell
      mediated immune response, followed by intratracheal instillation of deltaE1-E3
      replication-deficient adenovirus expressing mouse GM-CSF (Av1mGM). Mice were
      killed 1, 3, and 5 weeks after treatment to assess lungs for GM-CSF, surfactant
      protein B (SP-B), alveolar macrophage maturation, and type II cell proliferation.
      GM-CSF was detected in BAL fluid from GM-/- mice 1 week after Av1mGM treatment,
      and GM-CSF mRNA was detected by RT-PCR through 5 weeks. Five weeks after Av1mGM
      treatment, PAP was improved and SP-B decreased as assessed by ELISA and
      immunostaining. Increased numbers of alveolar macrophages stained with alpha
      naphthyl acetate esterase (alpha-NAE) following treatment with Av1mGM. Local
      expression of GM-CSF with a recombinant adenovirus ameliorated PAP in the GM-/-
      mice in association with enhanced maturation of alveolar macrophages.

PMID- 9759940
TI  - NIH Recombinant DNA Advisory Committee data management report. June 18-19, 1998.

PMID- 9759938
TI  - Impact of preexisting and induced humoral and cellular immune responses in an
      adenovirus-based gene therapy phase I clinical trial for localized mesothelioma.
AB  - Little is known about the immune responses induced by recombinant adenoviral (Ad)
      vectors in humans. The humoral and cellular immune responses were therefore
      analyzed in 21 patients with localized malignancy (mesothelioma), who received
      intrapleurally high doses of a replication-defective Ad5 vector carrying a
      suicide gene. Eight of 21 patients had pretreatment titers of neutralizing
      antibodies (NAb) to Ad at > or =1:100. Peripheral blood mononuclear cells (PBMCs)
      proliferated in response to adenoviral 5 structural proteins before treatment in
      17 of 21 patients. Preexisting humoral and cellular immunity did not preclude
      gene transfer. Vector instillation induced high titers of nonneutralizing and
      neutralizing anti-Ad antibody (4- to 341-fold increase in 18 of 20 patients) in a
      dose-dependent manner. Three patients generated antibodies to the transgene,
      herpes simplex virus thymidine kinase. Ad5-specific proliferation of PBMCs
      increased significantly (>3-fold) after vector administration in 12 of 21
      patients in a dose-dependent manner. Thus, replication-defective Ad5 administered
      intrapleurally induced significant humoral and cellular immune responses that
      induced no obvious adverse clinical sequelae.

PMID- 9759939
TI  - Evaluating the potential of germ line transmission after intravenous
      administration of recombinant adenovirus in the C3H mouse.
AB  - The goal of this study is to assess the likelihood that an adenoviral vector
      disseminated to gonads will be transmitted to offspring. This study is based on
      the observation that systemically administered vector can be detected in both
      ovaries and testes, using sensitive nested PCR techniques. Although the extent of
      vector dissemination to gonads is extremely small, as it is detectable only by
      nested PCR, it is unclear where it is located within these tissues and whether
      the DNA is capable of integration and transmission to offspring. A protocol was
      developed in C3H mice to address this question. Both male and female C3H mice
      were injected with a high dose of H5.001CBhOTC, an E1- and E4-deleted vector
      expressing human ornithine transcarbamylase. This dose of vector was sufficient
      to target 80% of hepatocytes (Gao et al., J. Virol. 1996; 70:8934-8943) and
      disseminate, at low levels, to both ovaries and testes in 94% of animals as
      determined by PCR. Vector-administered animals and controls were mated and 814
      offspring were evaluated for germ line transmission of the adenoviral vector by
      DNA hybridization of total cellular DNA extracted from the fetus. Southern blot
      analysis showed no evidence of germ line transmission in 578 offspring of crosses
      in which either one or both parents received recombinant adenovirus.

PMID- 9759941
TI  - Is the strategy of universal hepatitis B vaccination necessary in low-endemic
      countries?

PMID- 9759942
TI  - Time to relief of episodic symptoms of gastro-oesophageal reflux disease. A
      crossover comparison of single doses of the effervescent and standard
      formulations of ranitidine.
AB  - BACKGROUND: The length of time until symptom relief and the consistency of
      response are important aspects of the management of episodes of gastro
      oesophageal reflux disease (GORD). METHODS: In an open, randomized, crossover
      study 98 patients treated 3 episodes of GORD with ranitidine effervescent
      formulation and 3 with ranitidine standard formulation. The patients filled in a
      diary card during the 1st h after each study medication. Satisfaction with the
      formulations and the formulation of choice were determined at the end of the
      study. RESULTS: A higher percentage of episodes with acceptable symptom relief
      (82.4% versus 73.1% P=0.024) and a shorter time to acceptable symptom relief (27
      min versus 36 min; P < 0.001) were achieved with the effervescent formulation.
      Sixty-five per cent preferred the effervescent formulation (P < 0.01).
      CONCLUSIONS: An increased consistency of response and a more rapid symptom relief
      were achieved with treatment with the ranitidine effervescent formulation,
      indicating it may be more appropriate for on-demand treatment in patients with
      episodes of GORD.

PMID- 9759943
TI  - Prospective study of the effect of the Belsey Mark-IV fundoplication on reflux
      mechanisms.
AB  - BACKGROUND: Transient lower esophageal sphincter relaxations (TLESRs) are the
      major mechanism permitting gastroesophageal reflux (GER). Little information is
      available on how anti-reflux surgery affects reflux mechanisms, especially
      TLESRs. We evaluated the effects of partial fundoplication (Belsey Mark IV) on
      reflux mechanisms. METHODS: Sixteen patients were prospectively studied before
      and after Belsey Mark-IV operation by endoscopy, 24-h esophageal pH-metry, and
      simultaneous recording of pH and lower esophageal sphincter (LES) characteristics
      by sleeve manometry. RESULTS: The operation was successful in 14 of 16 patients
      (87%). Fasting and postprandial reflux decreased significantly (P < 0.01) after
      the operation. Partial fundoplication significantly (P < 0.05) decreased the
      number of TLESRs per hour in the fasting and postprandial period from 3.2+/-0.4
      and 5.6+/-0.5 to 1.7+/-0.3 and 2.8+/-0.4, respectively. The percentage of TLESRs
      associated with reflux also decreased significantly (P < 0.05). Basal LES
      pressure increased from 14.7+/-2.1 mmHg to 17.9+/-2.6 mmHg (not significant).
      CONCLUSIONS: Partial fundoplication controls GER through a reduction in the
      number of TLESRs and by decreasing the number of relaxations associated with
      reflux.

PMID- 9759944
TI  - Hyperplasia of gastric antral beta-microseminoprotein endocrine-like cells and
      increased serum levels of beta-microseminoprotein in atrophic corpus gastritis.
AB  - BACKGROUND: Beta-microseminoprotein is a 94-kDa protein present on most mucosal
      surfaces in the body. It is produced in mucin cells but is also found in a
      particular type of cells (E-cells) in the gastric antral mucosa. Most of these
      cells also contain gastrin. In atrophic corpus gastritis the gastrin-producing
      cells become hyperplastic, and the patients have hypergastrinemia. We wanted to
      ascertain whether there is a similar effect on the E-cells and on the
      concentration of beta-microseminoprotein in serum. METHODS: Antral biopsy
      specimens from 10 patients with atrophic corpus gastritis and 10 controls were
      stained immunohistochemically for beta-microseminoprotein and gastrin. beta
      Microseminoprotein and gastrin were measured by radioimmunoassay in serum from 15
      women with atrophic corpus gastritis and 31 healthy female blood donors. RESULTS:
      There was a 3.5-fold increase of the number of E-cells (which also were
      hypertrophic) and a 2.1 times higher serum concentration of beta
      microseminoprotein in the patients with atrophic corpus gastritis than in the
      control subjects. Gastrin was seen in 28% of the E-cells in patients with
      atrophic corpus gastritis, compared with 87% in normal antral mucosa. There was
      no correlation between the serum concentrations of beta-microseminoprotein and
      gastrin. CONCLUSIONS: In atrophic corpus gastritis antrum E-cells undergo
      hyperplasia and hypertrophy, and the proportion of E-cells containing gastrin
      decreases. Increased amounts of beta-microseminoprotein are secreted to the blood
      but uncorrelated with gastrin.

PMID- 9759945
TI  - Effect of sucralfate on gastric mucosal inflammatory responses induced by
      Helicobacter pylori lipopolysaccharide.
AB  - BACKGROUND: Helicobacter pylori lipopolysaccharide is emerging as a primary
      factor in the bacterium virulence, and its involvement in causing gastric mucosal
      responses typical of gastritis has recently been shown. In this study we
      investigated the effect of the antiulcer agent sucralfate on the expression of
      regulatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-4
      (IL-4), and epithelial cell apoptosis during H. pylori lipopolysaccharide-induced
      acute gastritis. METHODS: The experiments were conducted with rats pretreated
      intragastrically twice daily for 3 days with sucralfate at 100 mg/kg or the
      vehicle. The rats were then subjected to intragastric surface epithelial
      application of H. pylori lipopolysaccharide at 50 microg per animal and
      maintained on the sucralfate or vehicle regimen for an additional 4 days. The
      animals were killed 16 h after the last dose, and their gastric mucosal tissue
      used for histologic assessment, quantitation of TNF-alpha and IL-4 expression,
      and the assay of epithelial cell apoptosis. RESULTS: In the absence of
      sucralfate, H. pylori lipopolysaccharide induced acute mucosal responses
      characterized by the inflammatory infiltration of the lamina propria, hyperemia,
      and epithelial hemorrhage. This was accompanied by an 11-fold increase in gastric
      epithelial cell apoptosis and a 9-fold enhancement of the mucosal expression of
      TNF-alpha, but the level of IL-4 fell by 15%. Intragastric administration of
      sucralfate produced a 62% reduction in the extent of mucosal damage caused by H.
      pylori lipopolysaccharide, a 51% decrease in the mucosal expression of TNF-alpha,
      and a 7-fold reduction in the extent of epithelial cell apoptosis, whereas the
      expression of IL-4 increased by 52%. CONCLUSIONS: Gastric mucosal inflammatory
      responses to H. pylori lipopolysaccharide are characterized by a massive
      enhancement of the proinflammatory cytokine TNF-alpha and epithelial cell
      apoptosis and repression of IL-4. Our data also show that sucralfate is capable
      of inducing expression of the regulatory cytokine IL-4 and the suppression of
      apoptotic events triggered in gastric mucosa by the increase in TNF-alpha that is
      elicited by H. pylori lipopolysaccharide.

PMID- 9759946
TI  - Infection with Helicobacter pylori expressing the cagA gene is not associated
      with an increased risk of developing peptic ulcer diseases in Korean patients.
AB  - BACKGROUND: Helicobacter pylori strains possessing the cagA gene have been
      postulated to have a disease-specific relationship to peptic ulcer. The purpose
      of this study was to investigate the relationship between the infection with
      Helicobacter pylori expressing the cagA gene and the development of peptic ulcer
      diseases in Korean patients. METHODS: Genomic DNA and bacterial mRNA in the
      gastric mucosa were amplified by polymerase chain reaction (PCR) and reverse
      transcription PCR, using synthetic oligonucleotide primers to cagA genes to
      compare the prevalence of cagA genes in 35 patients with non-ulcer gastritis and
      99 patients with gastric or duodenal ulcer disease (53 and 46, respectively). Two
      different primer sets for the cagA gene were used. The first primer set amplified
      a 298-bp region (nucleotides 1751-2048), and the second set amplified a 349-bp
      region (nucleotides 1228-1249). RESULTS: The expected 298 and 349-bp PCR
      amplicons were identified as follows: 1) 32 (91.4%) and 30 (85.7%) of 35 non
      ulcer gastritis patients; 2) 5 1 (96.2%) and 50 (94.3%) of 53 benign gastric
      ulcer patients; and 3) 46 (100.0%) and 40 (87.0%) of 46 duodenal ulcer patients,
      respectively. CONCLUSION: These results strongly suggest that the cagA gene will
      not prove to be a useful marker to distinguish disease-specific H. pylori strains
      in the development of peptic ulcer diseases in Korean patients.

PMID- 9759947
TI  - National surveillance of Helicobacter pylori eradication therapy in Denmark.
      Results from registration of 34,582 prescriptions.
AB  - BACKGROUND: We wanted to characterize the use of Helicobacter pylori eradication
      therapy in Denmark (5,227,862 inhabitants). METHODS: All H. pylori eradication
      treatments from a nationwide database including all redeemed drug prescriptions
      in the period January 1994 to June 1996 were identified. So were all outpatients
      receiving a drug prescription for H. pylori eradication. RESULTS: We recorded
      34,582 prescriptions for H. pylori eradication therapy given to 28,784 patients.
      The incidence of new consumers was 220 per 10(5) inhabitants per year, with a
      maximum at 70-79 years of age. Eighty-six per cent of the patients had only one
      treatment course. In 16% of the eradication therapies, nonsteroid anti
      inflammatory drugs had been prescribed within the previous 3 months, and 45% had
      an anti-ulcer drug prescribed 1-12 months after the H. pylori eradication
      therapy. Consumption of antibiotics used for H. pylori eradication accounted for
      1.4% of the total consumption of antibiotics. CONCLUSIONS: The incidence of H.
      pylori eradication therapy was fairly stable but with changes in the pattern of
      drug regimens used. Anti-ulcer drugs were often given after H. pylori eradication
      therapy, suggesting an inappropriate use of treatment.

PMID- 9759948
TI  - Quality of life of adult coeliac patients treated for 10 years.
AB  - BACKGROUND: For patients with coeliac disease, adherence to a gluten-free diet
      (GFD) is essential to restore the intestinal mucosa. It is less clear whether
      this ensures well-being of the patient. We have therefore assessed aspects of the
      quality of life of adult coeliac patients who had been on a GFD for 10 years.
      METHODS: By means of the Short Form 36 Health Survey (SF-36), the subjective
      health status was measured in 89 adult coeliac patients (61% women) aged 35-74
      years. Patients shown to be in histologic remission (n=60) were evaluated by
      means of the Gastrointestinal Symptom Rating Scale (GSRS). RESULTS: The coeliac
      patients scored significantly lower in the SF-36 than general population, notably
      within the General Health and Vitality domains. The low scoring was confined to
      the female patients, who also reported significantly more gastrointestinal
      symptoms in the GSRS than the male coeliacs. The functional status and perceived
      health of the coeliac patients appeared unrelated to their biopsy findings.
      CONCLUSIONS: After 10 years on a GFD adult coeliac patients fail to attain the
      same degree of subjective health as the general population. This is particularly
      true for female patients and suggests that factors beyond normalization of the
      intestinal mucosa are of importance for the perceived health status of coeliacs
      diagnosed in adult life.

PMID- 9759949
TI  - Children with celiac disease express inducible nitric oxide synthase in the small
      intestine during gluten challenge.
AB  - BACKGROUND: Childhood celiac disease in Sweden is presently seen at an incidence
      of around 1/250 and is thus one of the commonest chronic diseases in children. It
      has recently been shown that children with untreated celiac disease have
      increased levels of nitrate/nitrite in the urine, most likely reflecting an
      increased production of nitric oxide in the inflamed mucosa. Nitric oxide is
      produced from L-arginine by an inducible or a constitutive nitric oxide synthase.
      The inducible nitric oxide synthase (iNOS) can be stimulated in various cells by,
      for instance, inflammatory mediators. The present study has been done to find a
      possible source of nitric oxide in the small intestine that could result in the
      increased levels of nitrate/nitrite in the urine in children with active celiac
      disease. METHODS: Small-intestinal biopsy specimens from children with active
      celiac disease were labeled with rabbit-anti-human antibodies to iNOS and
      visualized with fluorescent pig anti-rabbit antibodies. The specimens were then
      analyzed with confocal microscopy to assess the labeling pattern. RESULTS: In all
      of seven specimens from children with increased levels of nitrate/nitrite in the
      urine, we detected antibodies to iNOS, whereas in five of six control specimens-
      that is, from children with normal nitrate/nitrite levels--we could not detect
      any iNOS. CONCLUSIONS: Children with active celiac disease have a gluten-induced
      nitric oxide production in the small intestine reflected by increased urine
      levels of nitrate/nitrite and iNOS expression in the intestine. We conclude that
      the increased production of nitric oxide could presumably, directly or
      indirectly, result in injury of the small-intestinal tissue.

PMID- 9759950
TI  - Small-bowel mucosal inflammation in reticulin or gliadin antibody-positive
      patients without villous atrophy.
AB  - BACKGROUND: We investigated whether individuals with positive coeliac disease
      antibodies but without small-bowel villous atrophy have mucosal inflammation
      implicating gluten-sensitivity. METHODS: Small-bowel mucosal morphology; CD3+,
      alphabeta+, and gammadelta+ T-cell receptor-bearing intraepithelial lymphocytes;
      and mucosal HLA-DR expression were studied in 96 IgA-class antireticulin or
      antigliadin antibody-positive adults suspected of having coeliac disease and in
      27 control subjects. RESULTS: Villous atrophy compatible with coeliac disease was
      found in altogether 29 patients, in 18 of 21 (86%) patients with both
      antireticulin and antigliadin antibodies, in 9 of 15 (60%) patients with
      antireticulin antibodies only, and in 2 of 60 (3%) with antigliadin antibodies
      only. In 67 antibody-positive patients with normal villous architecture the
      densities of CD3+, alphabeta+, and gammadelta+ intraepithelial lymphocytes were
      significantly higher than in non-coeliac control subjects. Ten patients with
      initially increased densities of gammadelta+ T cells but normal villous structure
      underwent a follow-up biopsy after 4-18 months, which showed villous atrophy in
      five patients. CONCLUSIONS: IgA-class antireticulin or antigliadin antibody
      positive patients with normal small-bowel mucosal morphology frequently have
      immunohistochemical markers of coeliac disease latency. Together with our follow
      up data this implies that they may be gluten-sensitive.

PMID- 9759951
TI  - A prospective study of anal sphincter injury due to childbirth.
AB  - BACKGROUND: Faecal incontinence commonly affects women, principally because of
      childbirth. Our aims were to determine the functional effect of childbirth on the
      pressures generated by the anal sphincter and to determine the patterns of injury
      to the sphincter. METHODS: Anal manometry was performed in 53 primiparous women
      prenatally, in 50 women at a median of 5 weeks postnatally, and repeated in 26
      women at a median of 6 months postnatally. In addition, anal ultrasound was
      performed postnatally. Pelvic floor symptoms were assessed. The mode of delivery
      was examined to determine what variables affected anal function. RESULTS: Squeeze
      pressure was significantly reduced (P < 0.001) 6 weeks postnatally (mean, 170.4
      cm H2O; standard deviation (s), 56) compared with the prenatal value (mean, 225.6
      cm H2O; s, 58). This occurred in symptomatic and asymptomatic women and in women
      with a normal anal ultrasound. Resting pressure was significantly reduced at 6
      weeks (P < 0.001; prenatal mean, 91.6 cm H2O; s, 25; postnatal mean, 80.Ocm H2O;
      s, 21). Delivery method (vaginal or caesarean) was the only factor significant
      for the reduced squeeze pressure (r=53.377; standard error, 13.973; P < 0.001).
      Sphincter defects (41%) were common but did not influence anal sphincter
      function. CONCLUSION: Anal function was significantly affected by vaginal
      delivery with short-duration follow-up. This occurred with and without evidence
      of an anal sphincter injury. The importance of a sphincter injury is questioned.

PMID- 9759952
TI  - Body composition by dual-energy X-ray absorptiometry in patients with Crohn's
      disease.
AB  - BACKGROUND: To study body composition at the whole-body level in patients with
      Crohn's disease and a history of intestinal resection compared with healthy
      controls, we performed a cross-sectional study using dual-energy X-ray
      absorptiometry (DXA). METHODS: Thirty-one patients, 13 men and 18 women, were
      included. They had a history of Crohn's disease for a mean period of 20 years
      (range, 4-45 years). All patients had undergone intestinal resections. The colon
      had been resected in 24 patients, and the mean length of the resected small
      intestine was 97 cm (range, 0-305 cm). At the time of investigation the Crohn's
      disease had been in remission for at least 24 months. Patients presented with
      significantly increased faecal volume and faecal fat excretion. A group of 69
      women and 19 men were investigated with DXA and used as reference group. The fat
      free mass (FFM), fat mass (FM), percentage fat mass (FM%), and total body mineral
      content (TBMC) were measured by DXA, and the results were expressed as a z-score.
      RESULTS: The mean z-score of the body mass index (BMI) was significantly reduced
      to -0.35 (P=0.036). The FFM was significantly reduced with a mean z-score of 
      1.74 (P=0.0001). The FM was unchanged (z-score, 0.12; P=0.42). However, FM
      expressed as percentage of body weight was significantly increased, with a z
      score of 0.88 (P=0.001). The TBMC was significantly decreased, with a mean z
      score of -1.42 (P=0.0001). There was positive direct correlation between the BMI
      and TBMC z-scores. There was no correlation between malabsorption and body
      composition variables. CONCLUSION: Patients with clinically quiescent Crohn's
      disease showed significant changes in body composition, with low BMI, significant
      loss of FFM, and unchanged FM. However, when expressed as percentage of body
      weight, FM was significantly increased. The TBMC was significantly reduced.

PMID- 9759953
TI  - The inflammatory bowel disease questionnaire: a valid and reliable measure in
      ulcerative colitis patients in the North East of England.
AB  - BACKGROUND: The validity and reliability of the Inflammatory Bowel Disease
      Questionnaire (IBDQ) needed to be confirmed before its use in the UK. METHODS:
      The IBDQ was administered to 28 subjects with ulcerative colitis (UC) on 3
      separate occasions over a period of 4 weeks, twice by an interviewer and once by
      self-completion. Convergent and concurrent validity was assessed by using the
      Colitis Activity Index (CAI) and the Short Form 36 Health Survey (SF-36). Test
      retest reliability and internal consistency were also tested. RESULTS: There were
      moderately high Pearson correlations between related IBDQ domains and SF-36
      dimensions and also between the CAI score and the IBDQ Bowel domain and the SF-36
      Pain dimension. Cronbach's alpha, corrected item-total correlations, and intra
      class correlation coefficients were high. CONCLUSIONS: The IBDQ is a valid and
      reliable health-related quality of life scale for use in patients with UC and is
      suitable for use in the UK.

PMID- 9759954
TI  - An orally administered growth factor extract derived from bovine whey suppresses
      breath ethane in colitic rats.
AB  - BACKGROUND: Lipid peroxidation is a potential mechanism of bowel damage in
      colitis. The effect of oral consumption of a bovine whey-derived growth factor
      extract (WGFE) on lipid peroxidation was assessed using the ethane breath test in
      the dextran sulphate sodium (DSS) model of ulcerative colitis (UC) in rats.
      METHODS: Groups of rats consumed water (control), 2% DSS in drinking water, 2%
      DSS with a WGFE-supplemented diet, or 2% DSS plus prednisolone (1 mg x kg(-1) x
      day(-1)) for 6 weeks, changing to sulphasalazine (100 mg x kg(-1) x day(-1)) for
      the subsequent 4 weeks. Ethane breath tests were conducted on all animals on days
      2, 4, 6, 8, and 10 (acute phase) and weeks 3, 6, and 9 (chronic phase) after
      commencement of DSS consumption. RESULTS: There were no significant differences
      in ethane production between any groups during the acute phase. Ethane was
      significantly increased (P < 0.05) in rats consuming DSS alone in week 6 compared
      with control but had decreased to control levels by week 9. WGFE and conventional
      therapy were effective in suppressing ethane production in week 3. CONCLUSIONS:
      WGFE is as effective as conventional therapies at limiting ethane production and
      thus ostensibly colonic lipid peroxidation in the early phases of experimental
      chronic UC.

PMID- 9759955
TI  - Mucosal mitochondrial function and antioxidant defences in patients with gastric
      carcinoma.
AB  - BACKGROUND: Cancer cells have alterations in energy metabolism due to defective
      mitochondrial function. This may be due to generation of excessive free radicals
      and/or defective antioxidant enzyme systems. The aim of the present study was to
      assess mitochondrial function and antioxidant defences in the gastric mucosa of
      patients with gastric carcinoma (CA). METHODS: Gastric mucosal mitochondrial
      function was assessed by means of the reduction of tetrazolium dye (MTT), and
      levels of antioxidants such as glutathione S-transferase (GST), catalase,
      superoxide dismutase (SOD), and thiols were measured in biopsy specimens taken
      from the tumour mucosa (TM) and tumour-free (TF) mucosa, 2 cm away from the
      tumour, in 49 patients with gastric CA and compared with that in 54 controls. In
      a further 10 patients with gastric CA, these studies were done on TM and TF
      mucosa 2 cm and > or = 5 cm away from the tumour. In 10 patients and 5 controls,
      specimens were obtained for electron microscopy as well. Helicobacter pylori
      infection was diagnosed by means of histology. RESULTS: MTT reduction and GST and
      SOD activities were significantly decreased in TM and TF mucosa in patients with
      CA compared with controls (P < 0.01). The levels of thiols and catalase activity
      were significantly increased in CA as compared with controls (P < 0.01). H.
      pylori positivity did not influence most of these variables but did give
      significant decrease in MTT reduction in CA (TF) mucosa (P=0.01) and significant
      increase in thiol levels in CA (TM) mucosa (P=0.04). Electron microscopy showed
      mitochondrial alterations in tumour cells in all patients and in adjacent mucosa
      of 10%-50% of the cells. CONCLUSIONS: 1) In gastric CA the cancer mucosal cells
      and the non-involved cells adjacent to the tumour have defective mitochondrial
      function, which may be due to altered antioxidant defences and possibly altered
      free radical formation. 2) Ultrastructural mitochondrial abnormalities are shown
      to parallel these biochemical abnormalities.

PMID- 9759956
TI  - Pain patterns after distension of the gallbladder in patients with acute
      cholecystitis.
AB  - BACKGROUND: Visceral pain is characterized by poor pain localization and a
      referred or radiating pain pattern. Its clinical importance in the abdomen is
      stressed by the finding that about one-third of patients still complain of
      abdominal pain after cholecystectomy. A better understanding of symptoms arising
      from the gallbladder and the underlying pathophysiology is therefore desirable.
      The aim of the present study was consequently primarily to characterize the
      symptom patterns after distension of the gallbladder. Secondary aims were to
      describe the pressure-volume relation in the gallbladder and the cystic duct
      opening pressure. METHODS: Twelve patients (nine women, three men) treated with
      cholecystostomy for acute cholecystitis were investigated. Simultaneous
      cholescintigraphy and measurement of changes in intraluminal gallbladder pressure
      after injections of saline through a gallbladder catheter were performed. After
      each injection of saline the localization of pain and the presence of nausea and
      vomiting were registered. The injections continued until the patient felt
      abdominal pain necessitating cessation of the investigation or until the cystic
      duct opened (visualized on cholescintigraphy). RESULTS: Distension of the
      gallbladder caused pain in 10 of the 12 patients. In 70% the pain was localized
      under the right costal margin or in the epigastrium. No mathematical formula
      could describe the pressure-volume relation in the gallbladder. The cystic duct
      opening pressure varied between 3 and 44 mmHg. CONCLUSIONS: Pain caused by
      increased gallbladder pressure is localized mostly, but not always, under the
      right curvature and in the epigastrium. A substantial variation in cystic duct
      opening pressure was found.

PMID- 9759957
TI  - Prevalence of intrapulmonary vascular dilatations in normoxaemic patients with
      early liver cirrhosis.
AB  - BACKGROUND: The aim of this study was to determine the prevalence of
      intrapulmonary vascular dilatations (IPVD) in normoxaemic patients with early
      liver cirrhosis and to compare their occurrence in progressive alcoholic versus
      postviral hepatic insufficiency. METHODS: Pulmonary function tests and arterial
      blood gas measurements were performed in 75 consecutive patients with cirrhosis
      of alcoholic and postviral aetiology. Contrast-enhanced echocardiography was used
      to identify IPVD. RESULTS: All patients were grade A or B in accordance with the
      Child-Pugh modified classification. Arterial blood gas analyses showed
      normoxaemia in all patients. Eight of 75 patients (10.7%) had a positive contrast
      echocardiogram, all with a decreased diffusion capacity (D1CO < 75% of the
      expected value). The abnormality was more prominent with advancing stage of liver
      failure (4.5% in grade A versus 19.4% in grade B; P < 0.05) and more common in
      patients with alcoholic cirrhosis (17.5% in alcoholic versus 2.9% in postviral
      cirrhosis; P < 0.05). CONCLUSION: In normoxaemic patients with early liver
      cirrhosis subclinical pulmonary vasodilatation, as assessed with contrast
      echocardiography, can occur. The finding is more prominent in alcoholic cirrhosis
      and possibly reflects an advancing degree of liver insufficiency.

PMID- 9759958
TI  - Gallbladder contents and fasting gallbladder volumes during and after pregnancy.
AB  - BACKGROUND: A high risk of developing sludge or gallstones has been associated
      with pregnancy. The aim of this study was to relate the prevalence of sludge and
      gallstones during and shortly after pregnancy to fasting gallbladder volume as an
      indicator of gallbladder motility. METHODS: The population included 114
      apparently healthy pregnant women from the Outpatient Clinic of Obstetrics of a
      large regional hospital and from the practices of regional midwives.
      Ultrasonography of the gallbladder was performed at weeks 15, 25, and 35 of
      gestation and at week 3 and month 6 postpartum. RESULTS: At gestational week 15,
      3 women had gallstones and 10 had sludge (mean volume, 33.8 ml), and 99 women had
      a normal gallbladder (mean volume, 30.5 ml). At week 25, 1 woman with a normal
      gallbladder formed gallstones and underwent cholecystectomy shortly after, and 22
      women had sludge, of whom 13 had a normal gallbladder at first examination (mean
      volume, 33.2 ml). In 88 women with normal gallbladders (of whom 2 had sludge at
      week 15) mean volume was 31.9 ml. At week 35, 2 women had gallstones, and 21 had
      sludge (mean volume, 30.5 ml). In the remaining 79 women the gallbladders were
      clear (mean volume, 29.5 ml). Eight women developed sludge and two women
      gallstones in normal gallbladders at week 25. Seven women with sludge at week 25
      had a normal gallbladder at week 35. Three weeks postpartum only 10 of 100 women
      had sludge (mean volume, 29.1 ml). Of these 10, 9 women had a normal gallbladder
      at week 35. Twenty of 21 women with sludge at week 35 had normal gallbladders
      week 3 postpartum. Gallstones found at week 35 had disappeared. In the women with
      a normal gallbladder the mean volume was decreased to 19.7 ml (P < 0.0001). Six
      months postpartum, sludge was found in 6 (mean volume, 18.4 ml) of 93 women (mean
      volume, 20.3 ml), of whom 5 had a normal gallbladder at week 3 postpartum. Only
      61 women showed a normal gallbladder at each examination of the study. No
      differences in patient characteristics were found between women with normal
      gallbladders and those with sludge or gallstones. CONCLUSIONS: Fasting
      gallbladder volume was increased in all pregnant women. This could not explain
      the formation of sludge or gallstones during gestation. Decrement of gallbladder
      volumes after delivery was faster in normal, clear gallbladders. More than a
      prerequisite, increased fasting gallbladder volume seemed to be a permissive
      factor of pregnancy-associated gallstone formation.

PMID- 9759960
TI  - Delayed mid-ileal perforation secondary to acute-on-chronic ischaemia after a
      diagnostic colonoscopy.
AB  - Perforation occurring at a remote site of the bowel after diagnostic colonoscopy
      is rare. A 61-year-old man presenting with bloody diarrhoea underwent
      colonoscopy. A dynamic ileus developed in less than 1 day, and mid-ileal
      perforation occurred 7 days after the procedure. It is suggested that high air
      pressure during colonoscopy further compromised the reduced blood flow in the mid
      ileum, which had underlying chronic ischaemia, leading to perforation. Our
      patient constitutes the first reported case of small-bowel perforation after
      colonoscopy due to pre-existent ileal ischaemia.

PMID- 9759959
TI  - Serum pancreatic enzymes in human immunodeficiency virus-infected children. A
      collaborative study of the Italian Society of Pediatric Gastroenterology and
      Hepatology.
AB  - BACKGROUND: Numerous studies have shown pancreatic disease in adult human
      immunodeficiency virus (HIV)-infected patients, but there are very few reports on
      pediatric patients. Our aim was to determine the prevalence of increased serum
      pancreatic enzyme levels and their relationship to clinical manifestations of
      acute pancreatitis in HIV-infected children. METHODS: Forty-seven consecutive,
      symptomatic HIV-infected children (24 male; median age, 7.3 years; range, 1-17
      years) and 45 sex- and age-matched controls without gastroenterologic disease
      were enrolled. In all subjects serum total amylase, pancreatic amylase, and
      lipase were assayed with commercial kits. The following were recorded: disease
      progression (CDC class), nutritional status (weight Z-score), CD4 lymphocyte
      count, drug treatment during the previous 12 months, presence of opportunistic
      infections, clinical evidence of acute pancreatitis (increased serum pancreatic
      enzymes associated with vomiting, abdominal distention, and intolerance when
      eating). RESULTS: Ten of 47 HIV patients had increased serum total amylase
      values; however fewer patients had increased specific pancreatic enzymes: 6 of 47
      for pancreatic amylase (range, 1.8- to 19.8-fold normal limit) and 7 of 47 for
      lipase (range, 1.4- to 4-fold normal limit). Values were normal in all controls.
      Two HIV patients with increased total amylase had clinically evident parotid
      inflammation. None of the patients with increased serum pancreatic amylase and/or
      lipase had clinical symptoms of acute pancreatitis. Regression analysis showed no
      correlation between increased serum pancreatic enzyme levels and disease
      progression (CDC class), immunologic status (CD4 count), nutritional status, drug
      administration, or opportunistic infections. CONCLUSIONS: Fifteen per cent of HIV
      infected children had biochemical evidence of pancreatic involvement; however,
      this condition was unrelated to clinical signs of pancreatitis. Neither drug
      administration nor opportunistic infections seem to determine the increased serum
      pancreatic enzyme levels.

PMID- 9759961
TI  - Helicobacter pylori infection and progression of gastric atrophy and intestinal
      metaplasia.

PMID- 9759962
TI  - Percutaneous ethanol injection therapy for hepatocellular carcinoma in patients
      with ascites.

PMID- 9759963
TI  - The cell division cycle and the pathophysiology of Alzheimer's disease.
AB  - Evidence is growing of a role of apoptosis in neurodegenerative disorders
      including Alzheimer's disease. Recent research indicates that cell cycle
      disturbances may promote apoptosis in neurodegenerative diseases. In this
      commentary we will discuss the control of the cell cycle in mammalian cells in
      general and in the central nervous system in particular. We then summarize the
      evidence for cell cycle perturbations in Alzheimer's disease and discuss the
      possible significance these may have for the development of pathological changes
      in this disease. Our working hypothesis is that, contrary to previous belief,
      neurons in the adult human brain are capable of re-entering the cell division
      cycle. The progression of the cell cycle is normally arrested at an early stage
      and neurons are able to re-differentiate. However, in Alzheimer's disease the
      cell cycle is allowed to progress into the G2 phase. At this stage re
      differentiation is not possible and the neurons will suffer one of two fates:
      either they will die via an apoptotic pathway or they may produce Alzheimer-type
      pathology.

PMID- 9759964
TI  - The spike trains of inhibited pacemaker neurons seen through the magnifying glass
      of nonlinear analyses.
AB  - This communication describes the new information that may be obtained by applying
      nonlinear analytical techniques to neurobiological time-series. Specifically, we
      consider the sequence of interspike intervals Ti (the "timing") of trains
      recorded from synaptically inhibited crayfish pacemaker neurons. As reported
      earlier, different postsynaptic spike train forms (sets of timings with shared
      properties) are generated by varying the average rate and/or pattern (implying
      interval dispersions and sequences) of presynaptic spike trains. When the
      presynaptic train is Poisson (independent exponentially distributed intervals),
      the form is "Poisson-driven" (unperturbed and lengthened intervals succeed each
      other irregularly). When presynaptic trains are pacemaker (intervals practically
      equal), forms are either "p:q locked" (intervals repeat periodically),
      "intermittent" (mostly almost locked but disrupted irregularly), "phase walk
      throughs" (intermittencies with briefer regular portions), or "messy" (difficult
      to predict or describe succinctly). Messy trains are either "erratic" (some
      intervals natural and others lengthened irregularly) or "stammerings" (intervals
      are integral multiples of presynaptic intervals). The individual spike train
      forms were analysed using attractor reconstruction methods based on the lagged
      coordinates provided by successive intervals from the time-series Ti. Numerous
      models were evaluated in terms of their predictive performance by a trial-and
      error procedure: the most successful model was taken as best reflecting the true
      nature of the system's attractor. Each form was characterized in terms of its
      dimensionality, nonlinearity and predictability. (1) The dimensionality of the
      underlying dynamical attractor was estimated by the minimum number of variables
      (coordinates Ti) required to model acceptably the system's dynamics, i.e. by the
      system's degrees of freedom. Each model tested was based on a different number of
      Ti; the smallest number whose predictions were judged successful provided the
      best integer approximation of the attractor's true dimension (not necessarily an
      integer). Dimensionalities from three to five provided acceptable fits. (2) The
      degree of nonlinearity was estimated by: (i) comparing the correlations between
      experimental results and data from linear and nonlinear models, and (ii) tuning
      model nonlinearity via a distance-weighting function and identifying the either
      local or global neighborhood size. Lockings were compatible with linear models
      and stammerings were marginal; nonlinear models were best for Poisson-driven,
      intermittent and erratic forms. (3) Finally, prediction accuracy was plotted
      against increasingly long sequences of intervals forecast: the accuracies for
      Poisson-driven, locked and stammering forms were invariant, revealing
      irregularities due to uncorrelated noise, but those of intermittent and messy
      erratic forms decayed rapidly, indicating an underlying deterministic process.
      The excellent reconstructions possible for messy erratic and for some
      intermittent forms are especially significant because of their relatively low
      dimensionality (around 4), high degree of nonlinearity and prediction decay with
      time. This is characteristic of chaotic systems, and provides evidence that
      nonlinear couplings between relatively few variables are the major source of the
      apparent complexity seen in these cases. This demonstration of different
      dimensions, degrees of nonlinearity and predictabilities provides rigorous
      support for the categorization of different synaptically driven discharge forms
      proposed earlier on the basis of more heuristic criteria. This has significant
      implications. (1) It demonstrates that heterogeneous postsynaptic forms can
      indeed be induced by manipulating a few presynaptic variables. (2) Each
      presynaptic timing induces a form with characteristic dimensionality, thus
      breaking up the preparation into subsystems such that the physical variables in
      each operate as one

PMID- 9759965
TI  - Cellular mechanisms underlying two muscarinic receptor-mediated depolarizing
      responses in relay cells of the rat lateral geniculate nucleus.
AB  - We used the whole-cell recording technique in an in vitro preparation to examine
      the electrophysiological actions of the muscarinic receptors on relay cells in
      the rat lateral geniculate nucleus. Drop application of the muscarinic agonist
      acetyl-beta-methylcholine resulted in a slow depolarization that persisted for
      several minutes. The response was insensitive to the nicotinic antagonist
      hexamethonium, but was blocked by atropine, a muscarinic antagonist. The response
      was also insensitive to blockade of synaptic transmission by tetrodotoxin,
      indicating a direct muscarinic effect. The muscarinic depolarization consisted of
      two components that were somewhat separated in time. The early portion of the
      muscarinic response was mediated by a large inward current with little change in
      input resistance, while the later portion was mediated by a small inward current
      associated with a large increase in input resistance. Pharmacological agents were
      used to distinguish the two components. Drop application of McN-A-343, an ml
      receptor agonist, could only mimic the later component of the muscarinic
      response. This was supported by the result that the later component was blocked
      by low concentrations of pirenzepine. These data suggest that the ml receptor
      only mediates the late component of the muscarinic response, while the early
      component is mainly mediated by the m3 receptor. The idea that both ml and m3
      receptors were involved in the muscarinic depolarization was further supported by
      voltage-clamp analysis. This revealed that activation of the ml receptor was
      associated with a decrease in an inward potassium current, IKleak, while
      activation of the m3 receptor was likely associated with both a decrease in
      IKleak and an increase in the hyperpolarization-activated cation current Ih. In
      summary, our data suggest that muscarinic responses in geniculate relay cells
      result from the activation of two receptors, which modulate IKleak and Ih. Given
      the fact that the ascending aminergic systems also depolarize geniculate relay
      cells via two receptors acting on IKleak and Ih, we concluded that ascending
      activating systems use common mechanisms to enact the depolarizing form of
      arousal in relay neurons.

PMID- 9759966
TI  - Cholinergic excitation of dendrites in neocortical neurons.
AB  - Discharge patterns were studied in response to iontophoretic application of
      acetylcholine to the soma and dendrites of 128 neocortical pyramidal neurons of
      layer V. Extracellular recordings were obtained from slices of the guinea-pig
      parietal cortex. All responses found were excitatory and were better expressed in
      spontaneously firing cells than in silent ones. Sensitivity to acetylcholine was
      approximately the same at somatic and dendritic sites in all the cells.
      Activation of muscarinic receptors gave rise to firing patterns with equal
      latencies and intensities when applied to both soma and dendrites. The latter
      suggests that membrane excitation elicited in dendrites by binding of
      acetylcholine to muscarinic cholinoreceptors is likely to propagate towards the
      soma through intracellular biochemical processes. Modulating effect of
      acetylcholine on output firing patterns, elicited by dendritic application of
      excitatory amino acids, included shortening of the somatic response latency and
      increase of response intensity and duration. We propose that, in contrast to
      glutamatergic excitation, the spread of cholinergic excitation along dendrites
      involves intra-cellular chemical signalling and results in changing the
      electrical properties of dendrites all over their length.

PMID- 9759968
TI  - Multiple picrotoxinin effect on glycine channels in rat hippocampal neurons.
AB  - The effect of picrotoxinin on glycine-induced chloride currents was studied in
      dissociated rat hippocampal neuron culture in whole-cell and excised outside-out
      patches. Picrotoxinin blocked the glycine induced chloride currents. The
      picrotoxinin effect at 20 microM on glycine dose response relationship suggested
      a competitive mechanism. However, at 1 mM, the picrotoxinin effect was largely
      noncompetitive. In excised patches, glycine activated two types of channels
      distinguished by a difference in conductances. The first group had single channel
      conductances of around 47 pS and another around 100 pS. Occasionally, both types
      of channels were found in the same excised patch. Low concentration of
      picrotoxinin selectively blocked large conductance channels. At higher
      concentrations of 0.5 to 1 mM, picrotoxinin blocked the small conductance
      channels by a flickering block. These findings indicate that the whole-cell
      glycine current in rat hippocampal neurons is mediated by at least two types of
      channels. The two types of channels have distinct conductance, picrotoxinin
      sensitivity and different mechanism of picrotoxinin block.

PMID- 9759967
TI  - Histamine modulates high-voltage-activated calcium channels in neurons
      dissociated from the rat tuberomammillary nucleus.
AB  - The effects of histamine on high-voltage-activated Ca2+ channels in the
      histaminergic neurons acutely dissociated from the rat tuberomammillary nucleus
      were investigated in the nystatin-perforated patch recording mode under voltage
      clamp conditions. Histamine suppressed the high-voltage-activated Ca2+ channel
      currents in neurons which were positive for histidine decarboxylase with
      immunocytochemistry. The half-maximum inhibitory concentration and maximum
      inhibition were 2.6 x 10(-7) M and 16.6+/-1.90%, respectively. An H3 receptor
      agonist, R(-)-alpha-methylhistamine, mimicked the response to histamine, and
      thioperamide, an H3 receptor antagonist, inhibited the response to histamine. On
      the other hand, neither 2-methylhistamine, an H1 receptor agonist, nor dimaprit,
      an H2 receptor agonist, had a significant effect on the Ca2+ channel currents.
      Pretreatment with pertussis toxin blocked the inhibitory effect of histamine on
      Ca2+ channels, suggesting the involvement of Gi/Go proteins in the action of
      histamine. Omega-conotoxin-GVIA, omega-agatoxin-IVA, nicardipine, and omega
      conotoxin-MVIIC blocked the high-voltage-activated Ca2+ channel currents by 15.6,
      4.3, 27.1, and 31.2% of the total current, respectively, suggesting the existence
      of N-, P-, L-, and Q-type Ca2+ channels. A current that was insensitive to these
      blockers was also found. This residual current, "R-type", was completely
      suppressed by the addition of 200 microM Cd2+. Histamine significantly inhibited
      both the N- and P-type current components among these five types of Ca2+ channel
      currents. We concluded that histamine suppresses the N- and P-type Ca2+ channels
      in histaminergic neurons through an H3 receptor which is linked to a pertussis
      toxin-sensitive G-protein.

PMID- 9759969
TI  - The effects of 17beta-estradiol on ischemia-induced neuronal damage in the gerbil
      hippocampus.
AB  - The effects of 17beta-estradiol, a potent estrogen, on ischemia-induced neuronal
      damage, membrane depolarization and changes in intracellular Ca2+ concentration
      were studied in gerbil hippocampi. The histological outcome evaluated seven days
      after 3 min of transient forebrain ischemia in hippocampal CA1 pyramidal cells
      was improved by high doses of 17beta-estradiol (30 microg, i.c.v. and 4 mg/kg,
      i.p.), whereas low doses of 17beta-estradiol (3 and 10 microg, i.c.v.) showed no
      protective effect. Administration of 17beta-estradiol did not affect the changes
      in the direct current potential shift in ischemia in the hippocampal CA1 area at
      any dosage. A hypoxia-induced intracellular Ca2+ increase was evaluated by in
      vitro microfluorometry in gerbil hippocampal slices. Pretreatment of 17beta
      estradiol (4 mg/kg, injected i.p. 1 h before decapitation) suppressed the
      increase in the intracellular concentration of Ca2+ due to the in vitro hypoxia,
      affecting both the onset of the increase and the extent. The in vitro hypoxia in
      the Ca2+-free condition induced an elevation of the intracellular concentration
      of Ca2+, although the increase was gradual. Pretreatment of 17beta-estradiol (4
      mg/kg, i.p.) also inhibited this elevation. These findings imply that high doses
      of 17beta-estradiol protect the neurons from ischemia by inhibiting the release
      of Ca2+ from the intracellular Ca2+ stores, as well as by inhibiting the influx
      of Ca2+ from the extracellular space.

PMID- 9759970
TI  - Phencyclidine interferes with the hippocampal gating of nucleus accumbens
      neuronal activity in vivo.
AB  - The N-methyl-D-aspartate channel blocker phencyclidine is known to induce
      psychotic episodes in normal subjects and exacerbate psychosis in schizophrenics;
      however, its site of action is not clear. The prefrontal cortex, hippocampus, and
      basal ganglia are brain regions that appear to play a role in the pathophysiology
      of schizophrenia, and therefore are the most likely to be involved in the
      psychotomimetic action of phencyclidine. In this study, systemic administration
      of phencyclidine reduced the frequency and duration of the spontaneously
      occurring depolarized plateaus observed in the membrane potential of accumbens
      neurons recorded intracellularly in vivo. Furthermore, recordings from rats
      pretreated with phencyclidine yielded proportionately fewer neurons showing
      depolarized events compared with untreated animals. These results suggest that
      phencyclidine may interfere with the generation of the depolarized ("up") state
      of the accumbens neuron membrane potential, which we had previously shown is
      dependent upon hippocampal input and is necessary for action potential discharge
      in these neurons. This action of phencyclidine is proposed to impair the flow of
      cortical information through the nucleus accumbens, and thereby mimic the
      consequences of the hippocampal deficit proposed to contribute to the
      pathophysiology of schizophrenia.

PMID- 9759971
TI  - Axotomy-induced c-JUN expression in young medial septal neurons is regulated by
      nerve growth factor.
AB  - In the present study we investigated the axotomy-induced expression of the proto
      oncogene c-jun in young rat medial septal neurons and its regulation by nerve
      growth factor. First, medial septal neurons were retrogradely labelled by Fast
      Blue injection into the hippocampus at postnatal day 1 (P1). Rats of different
      developmental ages (P6, P9, P14, P21, P28 and P42) were then subjected to
      bilateral fimbria-fornix transection resulting in the axotomy of septohippocampal
      projection neurons. After the lesion, c-JUN immunoreactivity was observed in the
      nuclei of axotomized medial septal neurons of all stages examined, suggesting
      that c-JUN induction is an age-independent feature of axotomized medial septal
      neurons. Double immunolabelling for choline acetyltransferase and c-JUN or
      parvalbumin and c-JUN, respectively, revealed that both cholinergic and GABAergic
      septohippocampal projection neurons express c-JUN after axotomy. In addition, a
      co-localization of immunostaining for c-JUN and the neuropeptide galanin was
      found after lesion, as both proteins were induced in the same medial septal
      neurons following fimbria-fornix transection. Next, the regulation of c-JUN
      expression in axotomized medial septal neurons was studied in organotypic
      cultures of the medial septum. Axotomized medial septal neurons in culture did
      not express c-JUN in contrast to the in vivo situation. With the concept that
      nerve growth factor suppresses c-JUN expression, slice cultures of the medial
      septum were treated with antibodies against nerve growth factor. This treatment
      caused a dose-dependent increase in c-JUN-positive cells in these slice cultures.
      Simultaneous addition of nerve growth factor and antibodies against nerve growth
      factor resulted in the reversal of this effect. These data suggest an age
      independent induction of c-JUN in axotomized medial septal neurons and its
      regulation by nerve growth factor.

PMID- 9759972
TI  - The non-synaptic expression of transforming growth factor-beta 2 is neurally
      regulated and varies between skeletal muscle fibre types.
AB  - In adult skeletal muscles, transforming growth factor-beta 2 is restricted to the
      postsynaptic domain of the neuromuscular junction. The various putative functions
      of this transforming growth factor-beta 2 predict different patterns of
      transforming growth factor-beta 2 expression in denervated muscles. We therefore
      denervated rat tibialis anterior, extensor digitorum longus and soleus muscles
      and examined the expression of transforming growth factor-beta 2 using semi
      quantitative reverse-transcription polymerase chain reaction and
      immunohistochemistry. Denervation up-regulated transforming growth factor-beta 2
      expression extrasynaptically with little or no effect on synaptic expression. The
      up-regulation was detectable by one day, had become significant by three days and
      remained elevated for at least two weeks. This proves that the transforming
      growth factor-beta 2 associated with the neuromuscular junction is not under
      neural control and is consistent with transforming growth factor-beta 2 being a
      trophic factor for motoneurons. This pattern of transforming growth factor-beta 2
      expression is similar to that described for other proteins associated with the
      neuromuscular junction, notably the acetylcholine receptor subunit genes.
      However, in contrast to the acetylcholine receptor subunit genes, the extent of
      up-regulation of transforming growth factor-beta 2 varied between fibre types,
      with the glycolytic IIB fibres being less affected than other fibre types.

PMID- 9759973
TI  - Direct activation of the high-affinity nerve growth factor receptor by a non
      peptide symmetrical polyanion.
AB  - The high-affinity nerve growth factor receptor (gp140TrkA) is a tyrosine kinase
      receptor. The dimeric ligand, nerve growth factor, activates the receptor by
      stabilizing homodimer formation, which initiates transautophosphorylation.
      Suramin is a symmetrical planar polyanionic molecule which is being used as a
      novel experimental anti-neoplastic agent. Proposed mechanisms of the drug's anti
      proliferative activity include blocking mitogenic stimulatory growth factors or
      inhibition of tumor-specific cellular enzymes. In PC12 cells and in dorsal root
      ganglion neurons, suramin has been shown to act as a partial agonist for
      gp140TrkA. We now demonstrate direct activation of gp140TrkA by suramin using in
      vitro protein kinase assays and receptor dimerization studies. Additionally,
      activation of phosphatidylinositol-3-kinase by suramin and nerve growth factor
      was observed with 10-min exposure. The addition of anti-nerve growth factor
      antibodies along with suramin did not reduce the level of gp140TrkA
      phosphorylation, excluding induction of an autocrine loop of nerve growth factor
      release and activation. This demonstrates that a small polyanion can directly
      activate gp140TrkA via receptor dimerization. Our study reveals a suramin-induced
      homodimerization of gp140TrkA. This finding correlated with significant neurite
      outgrowth in naive PC12 cells exposed to the drug. Studies will be initiated to
      design structural analogs of suramin which possess neurotrophic properties with
      no associated neurotoxicity.

PMID- 9759974
TI  - Regulation of a site-specific phosphorylation of the microtubule-associated
      protein 2 during the development of cultured neurons.
AB  - The phosphorylation state of cytoskeletal proteins, including certain microtubule
      associated proteins, may influence the development and plasticity of axons and
      dendrites in mammalian neuron in response to appropriate extracellular stimuli.
      In particular, high molecular weight microtubule-associated protein 2, has been
      implicated in dendrite growth and synaptic plasticity and is thought to be
      modulated by phosphorylation and dephosphorylation. We have previously determined
      that threonines 1620/1623 on the microtubule-associated protein 2 molecule become
      phosphorylated in vivo and are targets for proline-directed protein kinases in
      vitro. Using the phosphorylated site-specific antibody 305, we now report the
      decreased phosphorylation state of high molecular weight microtubule-associated
      protein 2 during the development of cultured cerebellar granule neurons.
      Phosphorylation of high molecular weight microtubule-associated protein 2 at this
      site is significantly inhibited by lithium in short-term cultured neurons, which
      suggests the implication of glycogen synthase kinase-3. In long-term cultured
      neurons, it is also partially inhibited by PD098059, an inhibitor of
      extracellular signal-regulated protein kinase activation, which indicates an
      additional contribution of this kinase to high molecular weight microtubule
      associated protein 2 phosphorylation at this stage. Both in short-term and long
      term cultured neurons, okadaic acid augments high molecular weight microtubule
      associated protein 2 phosphorylation at this site through the inhibition of
      protein phosphatases 1 and/or 2A. Finally, glutamate receptor activation leads to
      a dephosphorylation of high molecular weight microtubule-associated protein 2 at
      this site which can also be effectively prevented by okadaic acid. These results
      are consistent with the participation of glycogen synthase kinase-3,
      extracellular signal-regulated protein kinases and protein phosphatases 1 and 2A,
      in the regulation of microtubule-associated protein 2 phosphorylation within
      living neurons, which may be modulated by extracellular signals like the
      neurotransmitter glutamate.

PMID- 9759975
TI  - Immunohistochemical evidence for dysregulation of the GABAergic system
      ipsilateral to photochemically induced cortical infarcts in rats.
AB  - Deficits of GABAergic transmission have been reported to occur in tissue
      surrounding ischemic cortical lesions between a few days and several weeks after
      the insult. In the present experiments, we used immunohistochemistry with
      antibodies against parvalbumin and two major subunits of the GABA(A) receptor
      (alpha1, alpha2) to characterize the events that underlie these changes at
      different levels of circuit organization. Neocortical infarcts (2 mm diameter)
      consistently affecting medial parts of the primary somatosensory cortex were
      induced photochemically in adult male Wistar rats; animals were allowed to
      recover for one week before perfusion-fixation. When compared to controls the
      pattern of immunoreactivity had changed for the al subunit of the GABA(A)
      receptor seven days after the insult. Ipsilateral to the ischemic lesions, we
      found a decrease in staining intensity reaching up to 4 mm laterally, resulting
      in a partial or complete absence of the normal laminar staining pattern. No
      consistent changes were observed for the alpha2 subunit. Parvalbumin staining
      revealed pathological alterations in a rim of tissue surrounding the infarct,
      measuring up to 1 mm from the border of the infarcts. Parvalbumin-positive
      interneurons in this region showed signs of degeneration; both a reduction of the
      number of dendrites and, to a lesser extent and only immediately adjacent to the
      ischemic lesions, a reduction of the number of parvalbumin-positive neurons was
      readily apparent. The results provide evidence for both a differential regulation
      of two GABA(A) receptor subunits and degenerative changes of parvalbumin
      containing interneurons ipsilateral to cortical infarcts. The relevance of these
      findings for mechanisms underlying long-term recovery, transient functional
      deficits and postinfarct seizures warrants further investigation.

PMID- 9759976
TI  - The role of nigrostriatal dopamine in metabotropic glutamate agonist-induced
      rotation.
AB  - Metabotropic glutamate receptors are a major class of excitatory amino acid
      receptors. Eight metabotropic glutamate receptors subtypes have been cloned and
      have been classified into three groups based on their amino acid sequence
      homology, effector systems, and pharmacological profile. Previous results have
      shown that striatal group I metabotropic glutamate receptor stimulation produces
      vigorous contralateral rotation in intact rats, thought to be due to increased
      striatal dopamine release. Examination of FOS-like immunoreactivity and local
      cerebral glucose metabolism suggests that this occurs secondary to activation of
      the subthalamic nucleus. We sought to determine the contribution of dopamine by
      examining metabotropic glutamate receptor agonist-induced rotation in rats
      following acute dopamine depletion by reserpine/alpha-methyl-para-tyrosine
      treatment, or chronic dopamine depletion by 6-hydroxydopamine treatment. In
      unilateral 6-hydroxydopamine lesioned rats, the group I metabotropic glutamate
      receptor agonist (RS)-3,5-dihydroxyphenylglycine induced contralateral rotation
      with a coincident increase in striatal 3,4-dihydroxyphenylacetic acid. The
      rotation was attenuated by the group I antagonist 1-aminoindan-1,5-dicarboxylate.
      Examination of FOS-like immunoreactivity and [14C]2-deoxyglucose uptake in
      chronically dopamine depleted rats also revealed similar patterns to those seen
      previously in intact rats. However, acutely dopamine depleted rats do not exhibit
      metabotropic glutamate receptor agonist-induced rotation and show a different
      pattern of [14C]2-deoxyglucose uptake, with no increase in glucose utilization in
      the intermediate and deep layers of the superior colliculus. These results
      suggest that there are compensatory changes under conditions of chronic dopamine
      denervation which permit metabotropic glutamate receptor agonist-induced rotation
      to occur, which may include dopamine receptor supersensitivity, increased
      dopamine turnover, and/or changes in sensitivity of striatal group I metabotropic
      glutamate receptors. The group III metabotropic glutamate receptor agonist L-(+)
      2-amino-4-phosphonobutyrate induced contralateral rotation in 6-hydroxydopamine
      lesioned rats, while it had no effect in intact rats. Additionally, examination
      of FOS-like immunoreactivity revealed a distinct pattern following L-(+)-2-amino
      4-phosphonobutyrate administration in 6-hydroxydopamine lesioned versus intact
      rats. These results suggest that there is a change in the effect of striatal
      group III stimulation under conditions of dopamine depletion.

PMID- 9759977
TI  - Birth insult increases amphetamine-induced behavioral responses in the adult rat.
AB  - We have previously reported that an apparently uncomplicated Caesarean section
      birth produces long-term alterations in steady-state levels of dopamine in the
      central nervous system of the rat. In addition, adult rats that had been born by
      Caesarean section, either with or without acute global anoxia, showed markedly
      greater dopamine release from the nucleus accumbens in response to repeated
      stress, in comparison to vaginally born controls. The aim of the present study
      was to test whether these birth complications also result in long-term changes in
      behavior mediated by dopamine systems. For this, we investigated effects of a low
      dose (0.5 mg/kg) of amphetamine on activity levels in three-month-old rats that
      had been born vaginally (control), by rapid Caesarean section, or by Caesarean
      section with 15 min of global anoxia. Amphetamine induced a significantly greater
      increase in locomotor activity in animals born by Caesarean section or by
      Caesarean section+ 15 min anoxia, in comparison to the drug's effects in
      vaginally born controls. Behavioral responses were further analysed from video
      recordings of the animals' behavior. In confirmation of automated activity
      counts, both animals born by Caesarean section and by Caesarean section + 15 min
      anoxia showed a significant increase in the duration and frequency of moving and
      a decrease in the duration and frequency of standing, in comparison to vaginally
      born controls. Animals delivered by Caesarean section showed a significant
      increase in the duration of sniffing and a decrease in the duration and frequency
      of grooming when compared to vaginally born controls. Animals delivered by
      Caesarean section + 15 min anoxia showed a significant increase in the duration
      and frequency of rearing, in comparison to controls. The pattern of behavioral
      changes observed indicates that, as adults, animals born by Caesarean section and
      by Caesarean section with added global anoxia both show heightened behavioral
      responses to amphetamine, in comparison to vaginally born animals. These findings
      highlight the sensitivity of dopamine pathways to variations in birth procedure
      and add experimental support to epidemiological evidence implicating birth
      complications in the pathophysiology of disorders involving central dopaminergic
      neurons, such as schizophrenia.

PMID- 9759978
TI  - Brain regional substrates for the actions of the novel wake-promoting agent
      modafinil in the rat: comparison with amphetamine.
AB  - Modafinil is a novel wake-promoting compound for which the mechanism and sites of
      action are unknown. We examined the neural substrates in the brain for the
      actions of modafinil using 2-deoxyglucose autoradiography and compared the
      findings to those obtained with amphetamine. Modafinil showed a relatively
      restricted pattern of changes in brain regional metabolic activity, while
      amphetamine altered glucose utilization in a wide variety of brain regions. Both
      modafinil and amphetamine increased glucose utilization in all subregions of the
      hippocampus (subiculum, CA1-CA3 and dentate gyrus) and in the centrolateral
      nucleus of the thalamus. Modafinil also increased glucose utilization in the
      central nucleus of the amygdala, but amphetamine had no effect in this region.
      Brain structures in which amphetamine increased metabolic rate but modafinil had
      no effect included regions of the basal ganglia, other nuclei of the thalamus,
      the frontal cortex, the nucleus accumbens, the ventral tegmental area and the
      pontine reticular fields. These findings suggest that, while both modafinil and
      amphetamine promote wakefulness, they act via distinctly different mechanisms.
      Modafinil appears to act on a specific subset of brain pathways which regulate
      sleep and wakefulness, whereas amphetamine affects a greater number of cerebral
      structures involved in the regulation of these behavioral states. Modafinil also
      lacks the pronounced effects on the extrapyramidal motor system which are
      characteristic of amphetamine and other psychomotor stimulants, implying that the
      effects of modafinil are not mediated by the dopamine system and that modafinil
      may selectively increase wakefulness with fewer side effects.

PMID- 9759979
TI  - Electrical and optical monitoring of alpha-latrotoxin action at Drosophila
      neuromuscular junctions.
AB  - Electrophysiological recording demonstrates that alpha-latrotoxin, a 125,000 mol.
      wt component of black widow spider venom, promotes high frequency quantal
      discharges at larval neuromuscular junctions of Drosophila. Concomitantly,
      fluorescence imaging of presynaptic calcium ion activity reveals that this toxin
      qualitatively elevates cytosolic ionized calcium in this preparation. These
      activities of alpha-latrotoxin are selectively antagonized by a monoclonal
      antibody, 4C4.1, that was previously shown to inhibit the action of this toxin in
      PC-12 cells. However, 4C4.1 does not block the release-promoting activity of gel
      filtered extracts of black widow spider venom. This indicates that black widow
      spider venom has multiple components that promote quantal transmitter secretion
      in invertebrates. This investigation demonstrates that alpha-latrotoxin is among
      the active principles in black widow spider venom that enhance transmitter
      release and raise cytosolic ionized calcium in Drosophila. These results suggest
      that Drosophila, because of the relative ease of genetic manipulation, may be
      useful to study the target protein(s) that mediate the binding and action of
      alpha-latrotoxin at nerve endings. Moreover, the procedure that we report for
      loading Drosophila nerve terminals with the calcium ion-sensing dye, Calcium
      Crimson, may have utility for studying calcium dynamics in mutant alleles with
      alterations in synapse development and function in this organism.

PMID- 9759980
TI  - Quantitation of neurokinin 1 receptor internalization and recycling in guinea-pig
      myenteric neurons.
AB  - Agonist-induced endocytosis and recycling of G protein-coupled receptors
      contributes to desensitization and resensitization of the receptors. In this
      study, we have used fluorescence immunohistochemistry, confocal microscopy and
      digital image analysis to quantify the proportion of receptor in the cytoplasm
      and on the surfaces of nerve cells in the guinea-pig ileum. With these methods we
      examined the dynamics of internalization of the neurokinin 1 receptor in response
      to agonist, return of receptor to the cell membrane and its capacity to be re
      internalized in response to further exposure to agonist. The basal level of
      neurokinin 1 receptor immunoreactivity in the cytoplasm was 12-15% of total
      cellular immunoreactivity. Concentration-response relations were generated for
      neurokinin 1 receptor internalization after incubation of isolated ileum with 10(
      11) to 10(-6) M substance P at 4 degrees C and warming to 37 degrees C for 20
      min. The threshold concentration for cytoplasmic receptor to exceed baseline was
      10(-11) M and the proportion of receptor in the cytoplasm increased with
      increasing substance P concentration. The effect of two exposures to agonist was
      studied using 10(-8) M and 10(-6) M substance P. After equilibration with
      substance P at 4 degrees C for 1 h followed by 20 min at 37 degrees C with no
      substance P, neurokinin 1 receptor immunoreactivity in the cytoplasm increased
      significantly from 12% to 36+/-3% for incubation with 10(-8) M and to 64+/-3% for
      10(-6) M. When return of receptor to the surface was blocked with monensin (10(
      5) M), 90% of the receptor was in the cytoplasm after 1 h at 37 degrees C
      following exposure to 10(-6) M substance P. After 60 min without substance P and
      no monensin, receptor in the cytoplasm decreased to 19+/-2% (10(-8) M) and 38+/
      4% (10(-6) M). A second period of equilibration with substance P at 4 degrees C
      for 1 h followed by 20 min at 37 degrees C, without substance P, resulted in a
      second wave of endocytosis; the fractions of receptor in the cytoplasm were 47+/
      2% (10(-8) M) and 70 2% (10(-6) M). These results indicate that most of the
      receptors on the cell surface are available for internalization and that the
      receptors that return to the cell surface after endocytosis rapidly regain their
      ability to bind ligand and undergo endocytosis.

PMID- 9759981
TI  - Angiotensin receptor antagonism with losartan and the regression of left
      ventricular hypertrophy.

PMID- 9759982
TI  - Reflux nephropathy and hypertension.
AB  - Renal scarring associated with vesico-ureteric reflux (VUR), most commonly
      detected in young children, is associated with a significant risk of developing
      hypertension in later life. Hypertension in reflux nephropathy contributes
      significantly to morbidity including deterioration of renal function. The
      mechanism of onset of hypertension is not clear although abnormalities of the
      renin-angiotensin system and sodium/potassium ATPase activity have been described
      in some cases. It is becoming clear that radiologically detectable renal scars or
      small kidneys may histologically indicate a variety of diagnoses. Prediction of
      the risk of developing hypertension in individual cases is difficult and
      therefore regular follow-up remains the only current means of recognising these
      subjects. Although prevention of renal scar development in children with VUR may
      offer some benefit in reducing the incidence of hypertension, there is no uniform
      action that can definitely achieve this, particularly in the very young, before
      any urinary infection occurs. Primary VUR seems to be a disorder with mendelian
      dominant inheritance and location of the gene may offer some hope of early
      identification within certain families. Timely introduction of preventative
      measures may then be possible even though reservations exist about their
      effectiveness.

PMID- 9759983
TI  - Effects of losartan on hypertension and left ventricular mass: a long-term study.
AB  - This study evaluated the anti-hypertensive efficacy, tolerability and effects on
      left ventricular mass of losartan, a selective angiotensin II receptor
      antagonist, after 22 months in patients with essential hypertension. The study
      included 77 hypertensive patients who were randomised at baseline to 22 months
      double-blind once-daily treatment with losartan 50 mg (L group n = 44 patients,
      mean age 54+/-9 years) or hydrochlorothiazide 25 mg (HCTZ group, n = 33 patients,
      mean age 56+/-7 years). Routine haematology, blood chemistry, standard
      electrocardiography, echocardiography and ambulatory non-invasive 24-h blood
      pressure (BP) monitoring were performed at baseline and after 10 and 22 months.
      The results showed good tolerability and a significant mean systolic and
      diastolic BP reduction in all groups (L group: 22 mm Hg and 11 mm Hg; HCTZ group:
      11 mm Hg and 7 mm Hg, respectively for systolic and diastolic mean BP). Moreover,
      a remarkable reduction in left ventricular mass index was reached after 10 and 22
      months only in the L group (L group: delta = -11 g/m2, P<0.02; HCTZ group: delta
      = -5 g/m2, P= 0.38). In conclusion, losartan was well tolerated and produced a
      significant reduction in BP and left ventricular mass in hypertensive patients

PMID- 9759984
TI  - Captopril, but not nifedipine, improves endothelium-dependent vasodilation in
      hypertensive patients.
AB  - The present study aimed to investigate the influence of the angiotensin
      converting enzyme (ACE)-inhibitor captopril and the Ca-antagonist nifedipine on
      endothelium-dependent vasodilation (EDV) in the forearm of hypertensive patients.
      Twenty-three middle-aged untreated hypertensive patients underwent evaluation of
      EDV and endothelium-independent vasodilation (EIDV) in the forearm, by means of
      local intra-arterial infusions of methacholine (MCh, evaluating EDV) and sodium
      nitroprusside (SNP, evaluating EIDV), before and 1 h after intake of either
      captopril (25 mg) or nifedipine (10 mg) in a randomised, double-blind fashion. A
      matched normotensive control group was investigated at baseline conditions only.
      Five of the hypertensives were also evaluated after 3 months of treatment with
      captopril 25 mg twice daily in an open pilot study. First, the vasodilation
      induced by methacholine (MCh), but not SNP, was significantly attenuated in the
      hypertensive patients compared to the normotensive controls (P < 0.001 at MCh 4
      microg/min). Second, although the two drugs induced a similar decline in blood
      pressure (BP) 1 h after administration (-11 to 10 mm Hg/-8 to 7 mm Hg), captopril
      significantly potentiated the vasodilator response to MCh (+32+/-13%, MCh 4 micr
      og/min, P < 0.01) but not SNP, while nifedipine did not significantly alter the
      response to either MCh or SNP. The improvement in vasodilator response to MCh
      induced by captopril was closely related to the reduction in BP (r = 0.72, P <
      0.01). Third, in the pilot study, 3 months of captopril treatment induced a
      significant potentiation of the vasodilator response to MCh (+34+/-17%, MCh 4
      microg/min, P < 0.05) in parallel with a significant BP reduction (-22+/-24/13+/
      13 mm Hg, P < 0.05), while the response to SNP was unchanged. In conclusion, the
      present study confirmed that essential hypertension is associated with a defect
      in EDV. Furthermore, an improvement in EDV was seen in hypertensive patients
      shortly after administration of captopril, but not nifedipine. In addition, a
      significant beneficial effect on EDV was seen in a small pilot study during long
      term treatment with captopril.

PMID- 9759985
TI  - Vascular and neuroendocrine components in altered blood pressure regulation after
      surgical repair of coarctation of the aorta.
AB  - STUDY OBJECTIVE: To investigate potential vascular and neuroendocrine
      determinants of altered blood pressure (BP) regulation in patients previously
      operated on for aortic coarctation. DESIGN, SETTING AND PATIENTS: We
      prospectively re-evaluated 45 patients operated on for aortic coarctation at
      Strasbourg University Hospital over a 13-year period. Four of these patients were
      less than 2 years old at the time of the operation and four were older than 20
      years. Patient age and time since the operation were on average 21+/-13 years and
      8+/-3 years, respectively. Surgery consisted of a resection with end-to-end
      anastomosis for 18 patients, angioplasty (8), prosthesis (4) or sub-clavian flap
      (15). RESULTS: Despite repair of the coarctation, about 40% of the patients
      showed an abnormal BP status at rest. The majority of these patients had
      uncomplicated borderline hypertension. The orthostasis test as well as the BP
      circadian rhythm were frequently abnormal. While the ankle/arm systolic pressure
      index measured at rest was generally within the normal range, diminished carotid
      femoral pulse wave velocity was observed. Plasma adrenaline and aldosterone
      levels were elevated in about 50% of the patients examined. CONCLUSIONS: These
      new findings suggest that there are 'cause and effect' relationships between
      aortic structural and functional vascular abnormalities, and augmented plasma
      adrenaline and aldosterone in some patients after coarctation repair. These
      phenomena are likely to be involved in altered BP regulation and might result in
      recurrent hypertension.

PMID- 9759986
TI  - Angiotensin-converting enzyme gene polymorphism in Nepal.
AB  - It has recently been found that there were very few hypertensives in the
      inhabitants of one Nepalese village, even though their salt consumption, per
      capita, was as high as citizens in many western countries. To evaluate the
      genetic factors involved in this phenomenon, we studied whether they had a
      special genotype distribution of angiotensin-converting enzyme (ACE) gene I/D
      polymorphism, which was recently reported to be involved in salt sensitivity. One
      hundred and thirty-eight subjects were evaluated in Nepal. Only nine subjects
      (6.5%) in this population were hypertensives (over 140/90 mm Hg) while consuming
      11 g salt/day, which confirmed the previous results. The distribution of
      genotypes and alleles of ACE gene I/D polymorphism was similar to that in the
      Japanese and Chinese, who had five-times more hypertensives while consuming
      almost as much salt as Nepalese, but significantly different from those in
      Caucasians. The present study reports, for the first time, the genotype
      distribution of ACE gene I/D polymorphism in Nepalese subjects. Furthermore, the
      results suggest ACE gene polymorphism may not be involved in the 'salt
      resistance' in this population.

PMID- 9759987
TI  - The direct costs to the NHS of discontinuing and switching prescriptions for
      hypertension.
AB  - There is much evidence to suggest that the treatment of hypertension reduces the
      risk of cardiovascular diseases and that it is cost-effective in most patients.
      However, the effectiveness of treatment relies on compliance and maintenance of
      treatment. Each pharmacological agent differs in terms of side effects. The
      existence of side effects can result in poor compliance and switching between
      treatments. A number of studies have reported high discontinuation rates for anti
      hypertensive therapies. This potentially imposes costs on the health service. The
      aim of this study is to use the MEDIPLUS data set to consider the cost arising
      from switching and discontinuation of therapy. The analysis will assess the
      resource costs in terms of extra GP visits and hospitalisations arising from
      individuals switching and discontinuing treatments. The total costs of
      hypertension were estimated to be around 76.5 m pound sterling per annum, of
      which 26.9 m pound sterling can be attributed to patients who switch or
      discontinue therapy.

PMID- 9759988
TI  - Hypertension in the elderly: attitudes of British patients and general
      practitioners.
AB  - The perceptions of patients and GPs of the risk of stroke in treated and
      untreated elderly hypertensives, and their attitudes towards anti-hypertensive
      therapy were examined. To explore attitudes of patients to the management of
      hypertension a qualitative approach was used, employing semi-structured
      interviews, with subsequent thematic analysis of the transcriptions. A
      questionnaire study of GPs' attitudes to the same subject was also conducted. The
      elderly (n = 75) greatly overestimate the risks of hypertension and the benefits
      of treatment. Most would accept anti-hypertensive therapy despite being informed
      of the true risks, citing confidence in their doctor as the major determinant in
      their decision. GPs (n = 121) were well informed of the risks and benefits, but
      less than half adhere to current guidelines. GPs should be aware how much the
      elderly overestimate the risks of hypertension and the benefits of its treatment.
      When considering treating hypertension in this group, patient contributions in
      the treatment decision-making process should be actively encouraged, especially
      as many elderly hold a deferential attitude towards their doctor. Patients should
      be informed of the risks of their disease and the benefits of treatment in terms
      they understand. The use of visual aids helps patients to grasp the difficult
      concepts of risk and benefit.

PMID- 9759989
TI  - Ambulatory systolic blood pressure patterns in elderly hypertensives.
AB  - In a recent study we found that patients with isolated systolic hypertension
      (ISH) had two patterns of systolic blood pressure (SBP) elevations by ambulatory
      BP monitoring (ABPM), sustained (S) and intermittent (I), the prognostic
      significance of which seems to be different. In the present study we tried to
      determine whether such patterns of SBP elevations may be detected among other
      hypertensives as well. Twenty-eight elderly patients (mean age 65.5+/-5.1 years),
      nine with ISH, 10 with systolodiastolic hypertension (SDH), and nine with white
      coat hypertension (WCH), underwent ABPM. Average clinic BP in the ISH group was
      184/83 mm Hg, in the SDH group 172/101 mm Hg, and in the WCH group 166/91 mm Hg,
      where as the ABPM averages were 169/80, 167/95 and 132/73 mm Hg, respectively,
      and differences held true for both daytime and night-time. Five ISH and four SDH
      patients had S patterns on ABPM, while the other four ISH and six SDH patients
      exhibited I patterns; none of the nine WCH subjects had either S or I patterns.
      ECG revealed left ventricular hypertropy (LVH) and/or ischaemic changes in eight
      patients with S patterns (ISH and SDH groups combined), as opposed to two
      patients with I patterns and only one patient of the WCH group. This seems to
      further suggest that an S pattern of SBP elevation on ABPM may have worse
      prognostic implications than either an I pattern or no SBP elevation.

PMID- 9759990
TI  - Blood pressure changes at the Dead Sea (a low altitude area).
AB  - The Dead Sea (barometric pressure: 800 mm Hg) is an important balneotherapeutic
      centre for chronic dermatologic and arthritic diseases. In the past, hypertensive
      patients have complained sporadically of weakness and dizziness during a stay in
      the Dead Sea. It was therefore recommended that hypertensives do not stay at
      these health centres. The aim of our study was to investigate the changes in
      blood pressure (BP) parameters of 72 hypertensive and normotensive osteoarthritic
      and rheumatoid arthritic elderly patients during a 2-week stay in the Dead Sea,
      and to further evaluate the effect of different balneotherapeutic means on these
      BP changes. Following a primary BP assessment at the out-patient clinic (Beer
      Sheva barometric pressure: 745 mm Hg), the patients were divided into four
      groups: (1)thermomineral pool; (2)Dead Sea water baths; (3) combination of the
      aforementioned treatments; and (4) controls (no balneotherapy). We demonstrated
      that the systolic BP (SBP) of hypertensives and normotensives decreased by an
      average of 17 mm Hg and that diastolic BP (DBP) decreased by an average of 8 mm
      Hg from their basic clinic-measured values. These favourable results were
      sustained during the first 10 days duration, and by the end of their stay they
      had diminished slightly. Thermomineral water had an additional lowering effect on
      the BP of the normotensives, but the SBP of hypertensives increased. Immediately
      following Dead Sea bath immersion, we noted a temporary increase of SBP in
      normotensives only. No patient, hypertensive or normotensive, complained of
      dizziness, malaise, or any other complaint. In our experience, patients feel well
      at low altitudes, and there is no justification in upholding hypertension as a
      contraindication to balneotherapy in the Dead Sea.

PMID- 9759991
TI  - Treatment of elderly patients with isolated systolic hypertension with isosorbide
      dinitrate in an asymmetric dosing schedule.
AB  - Nitrates decrease pulse pressure more than mean arterial pressure (MAP) and are
      advocated for the treatment of isolated systolic hypertension (ISH). Nitrates
      show drug tolerance during chronic treatment so an asymmetric dosing regimen may
      prevent loss of effect of nitrates. This study investigates the anti-hypertensive
      effect of isosorbide dinitrate (ISDN) given in a twice daily asymmetric dosing
      regimen in elderly patients with ISH. After a 6-week placebo run-in period,
      patients entered the double-blind study. Ten patients received placebo and 11
      patients ISDN 20 mg b.i.d. for 8 weeks. This dose could be doubled once. Office
      systolic and diastolic blood pressures (SBP/DBP) and ambulatory BP were measured.
      Pulse pressure was calculated as SBP-DBP. Office pulse pressure was more reduced
      during ISDN (17.9%) than with placebo (5%; P < 0.05). SBP and MAP decreased
      compared to baseline, but the changes were not statistically significant between
      the two groups. DBP tended to increase with ISDN compared to placebo. Mean 24-h,
      mean daytime and mean night-time pulse pressure decreased after treatment with
      ISDN (10.7%, 12.1%, 7.9%, respectively). Pulse pressure tended to decrease more
      during the day than during the night with ISDN. No changes could be demonstrated
      with placebo. In conclusion, pulse pressure decreased with ISDN, resulting in a
      lower SBP without a decrease in DBP. The latter may preserve coronary perfusion
      in ISH. With the asymmetric dosing regimen the decrease in pulse pressure was not
      clear at night. Whether a decrease in nocturnal BP, in addition to the
      spontaneous decrease, is advisable in ISH remains a matter of debate.

PMID- 9759992
TI  - Valsartan and atenolol in patients with severe essential hypertension.
AB  - The aim of this study was to evaluate the efficacy and tolerability of valsartan,
      a new angiotensin II receptor antagonist, versus atenolol in the treatment of
      severe primary hypertension. A total of 103 adult out-patients were randomised to
      receive either valsartan 160 mg or atenolol 100 mg once daily for 6 weeks. If
      necessary, additional blood pressure (BP) control could be provided as add-on
      therapy. Both valsartan and atenolol decreased mean sitting diastolic BP (DBP)
      and mean sitting systolic BP (SBP): least squares mean change from baseline in
      DBP; valsartan, -20.0 mm Hg; atenolol, -20.4 mm Hg: in SBP; valsartan, -30.0 mm
      Hg; atenolol, -25.5 mm Hg. There was no statistically significant difference
      between the treatment groups. Add-on hydrochlorothiazide (HCTZ) 25 mg was
      required by 97.2% of patients receiving atenolol and 83.6% of patients receiving
      valsartan; additional verapamil SR 240 mg was also required by 58.3% of patients
      receiving atenolol and 64.2% receiving valsartan. Valsartan was well tolerated,
      with a comparable incidence of treatment-related adverse experiences in both
      groups. In conclusion valsartan 160 mg is as well tolerated and effective as
      atenolol 100 mg in lowering BP in severely hypertensive patients.

PMID- 9759993
TI  - Cerebellar infarction as a complication of malignant hypertension.

PMID- 9759994
TI  - Non-pharmacological treatment of hypertension: a survey of 2150 general
      practitioners and internists.

PMID- 9759995
TI  - Molecular alterations in bladder cancer.
AB  - In recent years, significant information has been accumulated on the molecular
      alterations that take place during development of transitional cell carcinoma
      (TCC). A number of studies aimed at defining loss of heterozygosity have shown a
      general chromosomal instability in TCC with loss of parts of chromosome 9 at
      early stages of papillomas, and of chromosomes 11, 13, 3, 4, 8, 17 and 18 during
      further development of the tumor. Oncogenes are activated, exemplified by
      mutations in the ras gene family and overexpression of the c-erbB-2 gene, in a
      minor fraction of tumors. Alterations of tumor suppressors (involved in control
      of the cell cycle, DNA quality control and activation of apoptosis) seem to be
      frequently involved. Among these p53 has a key role, and one p53 allele is
      frequently lost in TCC followed by mutation of the remaining allele.These
      alterations are correlated with survival, disease progression, invasion and
      recurrence. Also frequently lost are the cell cycle control genes p16 and p15.
      The predictive value of this has not yet been determined. Studies of
      glycosylation genes have shown downregulation of the ABO gene, followed by loss
      of ABO blood group structures and accumulation of the Lewis cell adhesion
      molecules in high grade tumors. Functional proteome analysis has furthermore
      identified biomarkers that are correlated with grade and stage. Molecular models
      for TCC development can now be built, and clinical testing of these is urgently
      needed.

PMID- 9759996
TI  - Reciprocal expression of bcl-2 and p53 oncoproteins in urothelial dysplasia and
      carcinoma of the urinary bladder.
AB  - In order to investigate if and when the bcl-2 oncoprotein is activated in bladder
      tumorigenesis and its relationship with p53 overexpression and patient survival,
      we studied bcl-2 and p53 expression immunohistochemically in matched normal
      urothelium, dysplasia and cancer specimens selected by step-sectioning from 54
      radically resected bladders for non-metastatic transitional cell carcinoma (TCC).
      In normal urothelium and mild dysplasia, bcl-2 was restricted to the basal cell
      compartment, while in moderate and severe dysplasia its expression was detectable
      also in the upper regions. Excess bcl-2 immunoreactivity was found in 27 (50%) of
      carcinomas, and a larger proportion of high-grade TCCs showed bcl-2 expression
      compared with that of low-grade TCCs (P < 0.05). Overexpression of p53 protein
      showed a increasing trend toward the progression of bladder tumorigenesis (P <
      0.01) and a significant reciprocal correlation was found between bcl-2 and p53
      expression in either various dysplasias (P < 0.01) or carcinoma (P < 0.05). With
      the evolution from mild dysplasia to carcinoma in individual cases, loss of bcl-2
      expression was more frequently observed in superficial (P < 0.02) or low-grade
      carcinoma (P < 0.05) than in muscle-invasive or high-grade carcinoma.
      Furthermore, patients with negative immunostaining for both bcl-2 and p53 in
      cancer lesions had a significantly more favorable prognosis compared with those
      with positive immunostaining for the oncoproteins (P < 0.05), although bcl-2 by
      itself did not predict patient survival. We suggest that aberrant activated bcl
      2, which is seen earlier than p53, appears to facilitate bladder tumorigenesis
      and to enhance tumor aggression in some extent.

PMID- 9759997
TI  - 7-N-(2-([2-(gamma-L-glutamylamino)-ethyl]-dithio)-ethyl)-mitomycin C (KW-2149) is
      more active than mitomycin C on chemonaive and drug-resistant urothelial
      carcinoma cells.
AB  - This in vitro study aimed to investigate the cytotoxic activity of 7-N-(2-([2
      (gamma-L-glutamylamino)ethyl]dithio)ethyl)-mitomycin C (KW-2149) versus mitomycin
      C (MMC) against cell lines from human transitional cell carcinoma (TCC). Direct
      cytotoxicity of the two drugs was measured employing a colorimetric cytotoxicity
      assay on chemonaive and chemoresistant cancer cell populations. The results
      revealed that all cell lines (n = 19) were significantly more inhibited by
      treatment (2 h, 96 h) with KW-2149 than by MMC (P < 0.03-0.001). pH 6.0 decreased
      the stronger activity of KW-2149 (P < 0.013-0.004). Creatinine > or =10 mmol/l
      and nitrosourea > or =100 mg/l also inhibited the activity of KW-2149
      significantly. Tumor cells with relative drug-resistance against MMC (RT112-MMC:
      55-fold) exerted minor cross-resistance to KW-2149 (fourfold). In conclusion, the
      present in vitro data suggest KW-2149 to be a superior drug for intravesical
      therapy of patients with primary or recurrent superficial bladder carcinoma.
      Since pH and concentrations of creatinine and nitrosourea influence the activity
      of KW-2149, patients are supposed to profit from neutralizing the urinary pH and
      enhanced diureses.

PMID- 9759998
TI  - Induction of drug-resistant bladder carcinoma cells in vitro: impact on
      polychemotherapy with cisplatin, methotrexate and vinblastine (CMV).
AB  - Residual tumor, tumor progression or relapse after chemotherapy of patients with
      advanced or metastasized transitional cell carcinoma of the bladder (TCCB) are
      suggested to reflect intrinsic drug resistance of cancer cells, or the
      development of chemotherapy-resistant tumor cell populations. The present study
      aimed to establish drug-resistant subculture cell lines from human TCCB, selected
      for anticancer drugs, administered in the cisplatin, methotrexate and vinblastine
      (CMV) polychemotherapy protocol. Tumor cells from chemonaive cell lines of human
      TCCB (HT1376, TCCSUP) have been exposed to progressively increasing
      concentrations of cis-diamminedichloroplatinum (II) (CDDP), methotrexate (MTX),
      vinblastine (VBL) or etoposide (VP16). The resulting drug-resistant subculture
      cell lines (HT1376-CDDP, HT1376-MTX, HT1376-VBL, HT1376-VP, TCCSUP-CDDP, TCCSUP
      MTX, TCCSUP-VBL, TCCSUP-VP) were analyzed with regard to the achieved resistance
      factor (RF) for the inductive anticancer agent, the acquisition of cross
      resistance, DNA content, cell cycle distribution and cellular morphology.
      Parental HT1376 cells were intrinsically less sensitive to all anticancer drugs
      (1.7-50x), compared with TCCSUP cells. Relative resistance against the inductive
      anticancer agents was similar for the final drug-resistant subculture cell lines
      of both parental cell lines concerning CDDP and VP-16 (RF: 4-5x), but were
      reciprocal for MTX and VBL, respectively. MTX led to much stronger resistance (RF
      > 200) than the other drugs (RF < 10). Pleiotropic cross-resistances were
      observed in six out of eight (75%) drug-resistant subculture cell lines. Highest
      RF (50-500x) and frequency of cross-resistance (five of six cell lines) occured
      for MTX, and the least from exposure to CDDP (one of six cell lines). Overall,
      the results corroborated the central role of CDDP against urothelial carcinoma
      whereas repetitive applications of MTX appeared to be a doubtful strategy.
      Moreover, the experiments provide the largest panel so far of drug-resistant cell
      lines of human TCCB. They represent an appropriate tool for basic research on
      drug-resistance mechanisms, for the development and screening of future
      anticancer drugs or to elaborate strategies to overcome drug resistance for those
      patients who ultimately fail to respond to standard chemotherapy.

PMID- 9760000
TI  - Cactus flower extracts may prove beneficial in benign prostatic hyperplasia due
      to inhibition of 5alpha reductase activity, aromatase activity and lipid
      peroxidation.
AB  - The cactus flower is deemed to be helpful in benign prostatic hyperplasia (BPH)
      therapy, although there is no published information regarding its clinical effect
      in patients and on the mechanism of its biological activity. The present study
      evaluated the ability of cactus flower extracts to exert an effect on BPH through
      possible inhibition of such processes as lipid peroxidation, androgen
      aromatization and testosterone reduction. Cactus flower extracts indeed inhibited
      aromatase and 5alpha reductase activity in cultured foreskin fibroblasts, and
      also in human placental and prostatic homogenates. The inhibitory activity in
      both instances was associated with the dichloromethane or ethanol (methanol)
      extracts, while a marked antioxidative activity was associated with the aqueous
      extract. The finding that cactus flower extracts interfere concurrently in vitro
      with aromatase and reductase activity as well as with free radical processes
      suggests that these substances may prove beneficial in BPH treatment.

PMID- 9759999
TI  - Expression of gonadotropin-releasing hormone (GnRH) and GnRH receptor mRNA in
      prostate cancer cells and effect of GnRH on the proliferation of prostate cancer
      cells.
AB  - The purpose of this study was to determine the production of gonadotropin
      releasing hormone (GnRH), the co-occurrence of GnRH receptors in prostate cancer
      cells, and the effect of GnRH on prostate cancer cell proliferation. Four human
      prostate cancer cell lines were studied. LNCaP is an androgen sensitive prostate
      cancer cell line, DU-145 and PC-3 are androgen resistant, and TSU-Pr1 is
      uncharacterized. The expression of GnRH and GnRH receptor mRNAs were assessed by
      in situ hybridization and the effect of exogenous GnRH on proliferation of
      prostate cancer cells was measured by thymidine incorporation assay. GnRH mRNA
      expression, determined by in situ hybridization, was found in 83.48% of the
      LNCaP, 89.7% of the TSU-Pr1, 86.2% of the PC-3 and 95.3% of the DU-145. Signals
      of GnRH receptor mRNA were detected in more than 95% of the cells of all four
      cell lines. The proliferation of the prostate cancer cells grown in media
      supplemented with peptide hormone lacking charcoal-stripped serum was
      significantly (P < 0.05) suppressed. No significant effect of GnRH on the
      proliferation of all four prostate cancer cells was observed. In summary,
      prostate cancer cells produced GnRH and its receptors, and exogenous GnRH
      treatment did not affect the prostate cancer cell proliferation. The existence of
      GnRH and GnRH receptor mRNA in the same cell suggests that the role of GnRH
      produced by prostate cancer cells would be autocrine.

PMID- 9760001
TI  - Quantitative analysis on the localization of chondroitin sulfate proteoglycan in
      renal tissues of patients with calcium nephrolithiasis.
AB  - Previous studies have shown a significant decrease of heparin sulfate
      proteoglycan (HSPG) in the basement membrane of the glomerulus and the mucosa of
      the ureter/renal pelvis in patients with calcium nephrolithiasis. In this study,
      we looked at the localization of another influential proteoglycan, chondroitin
      sulfate (CSPG), using similar study groups by indirect immunofluorescence
      staining. Microscopic images were digitized and image analysis was used to
      quantitate the staining intensity of CSPG present in the basement membrane of the
      nephron. Our data showed significant loss of CSPG in the Bowman's capsule and the
      basement membrane of the mucosa of the ureter/renal pelvis using Mann-Whitney U
      Wilcoxon Rank Sum W test with P-values of 0.0043 and 0.0041, respectively.
      However, absence of staining was noted in the basement membrane of the glomerulus
      and no significant change in the basement membrane of the tubular epithelium was
      observed. In conclusion, our results showed changes in the localization of CSPG
      in the basement membrane of the nephron, accompanied with HSPG, which may
      contribute to the pathological condition of calcium nephrolithiasis.

PMID- 9760002
TI  - The effect of urease inhibitors on the encrustation of urethral catheters.
AB  - Encrustation and blockage of indwelling urethral catheters is primarily brought
      about by infection of the urinary tract by Proteus mirabilis or other urease
      producing species. The bacteria colonise the catheter forming a biofilm community
      within a polysaccharide matrix. The activity of the urease drives up the urinary
      pH and causes the crystallisation of calcium and magnesium phosphates in the
      biofilm. We have used a simple physical model of the catheterised bladder to
      investigate the ability of urease inhibitors to control encrustation. It was
      observed that acetohydroxamic acid (1.0 mg/ml) and fluorofamide (1.0 microg/ml)
      restricted the increase in pH of P. mirabilis-infected urine from 9.1 to 7.6.
      Significant reductions in the deposition of calcium and magnesium salts were also
      recorded on the silicone catheters. Electron microscopy confirmed that
      encrustation and occlusion of the catheter lumen was minimal in the presence of
      the urease inhibitors. The data from this in vitro study suggests that urease
      inhibitors, particularly fluorofamide, could have clinical applications in the
      prevention of catheter encrustation and blockage.

PMID- 9760003
TI  - Guiding spontaneous tissue regeneration for urethral reconstruction: long-term
      studies in the rabbit.
AB  - We designed long-term in vivo experiments to study rabbit urethral regeneration
      and remodelling over a hyaluronan biodegradable prosthesis. Seven months after
      the resection of a 1.5-cm-long tract of the urethra and its substitution with the
      prosthesis, radiological analysis showed the disappearance of the implant and the
      re-establishment of urethral continuity along the transmural defect. The
      regenerated tissue remodelled around the implant and exhibited good
      distensibility under pressure. Histological evaluation showed that the neo
      urethra was lined with transitional epithelium and the stroma contained abundant
      elastic fibres. An examination of the pattern of the major cytoskeletal and
      cytocontractile proteins of smooth muscle cells and fibroblasts was able to
      distinguish fibroblasts from smooth muscle cells and myofibroblasts in the neo
      urethra. These experiments provide evidence for the potential, successful use of
      biocompatible/bioresorbable devices for reconstructive surgery of the urethra.

PMID- 9760004
TI  - Elevated tubular proteinuria, albuminuria and decreased urinary N-acetyl-beta-D
      glucosaminidase activity following unilateral total ureteral obstruction in rats.
AB  - Urinary tubular proteinuria and N-acetyl-beta-D-glucosaminidase (NAG) activity
      has not yet been studied after unilateral total ureteral obstruction (UTO). The
      aim of the study was (1) to evaluate in a longitudinal study (7 weeks) the
      behaviour and the potential clinical value of tubular proteinuria and urinary NAG
      activity after UTO; (2) to study the physiopathology of the non-obstructed
      contralateral kidney by using these two different markers of tubular damage.
      METHODS: in 28 female, adult Wistar rats (UTO: n = 16, sham: n = 12), tubular
      proteinuria and urinary NAG activity were measured before and 1 and 5 weeks after
      surgery. RESULTS: a significant (P < 0.01) increase in tubular
      proteinuria/creatinine ratio and urinary creatinine and a decrease in urinary NAG
      activity was found 1 week after UTO. All parameters normalized after 6 weeks.
      Albuminuria increased progressively (P < 0.01) during the study. CONCLUSION:
      tubular proteinuria increases during the first week following UTO in rats. The
      initial increase of low molecular weight proteins following UTO is not due to
      tubular damage as no parallel increase of urinary NAG was found. We suggest an
      initial tubular overperfusion with primary urine, due to an increased single
      nephron glomerular filtration and overruling the reabsorption capacity of the
      proximal tubules.

PMID- 9760005
TI  - CYP2E1 genotyping in renal cell/urothelial cancer patients in comparison with
      control populations.
AB  - OBJECTIVE: Genetic polymorphisms in enzymes involved in carcinogen metabolism
      have been found to influence susceptibility to cancer. Ethanol-inducible CYP2E1
      is an enzyme of major toxicological interest because it metabolizes several
      drugs, precarcinogens, and solvents to reactive metabolites. In the present
      investigation, we studied the cytochrome P450 2E1 genetic polymorphism in renal
      cell/urothelial cancer patients in comparison with healthy control populations in
      the regions of Jena and Halle in Germany. PATIENTS AND MATERIAL: DNA of
      peripheral white blood cells was isolated both from 273 renal cell/urothelial
      cancer patients and 298 controls from the regions of Jena and Halle. METHOD: We
      focused on polymorphisms in the promoter region and intron 6 of the CYP2E1 gene.
      The polymorphims were identified as restriction fragment length polymorphisms
      (RFLPs) by polymerase chain reaction (PCR) and subsequently applying the
      restriction enzymes PstI/RsaI and DraI. RESULTS: In the region of Jena as well as
      of Halle, the frequency distributions of the PstI/RsaI, DraI, and combined DraI +
      PstI/RsaI genotypes showed no significant differences between controls and renal
      cell/urothelial cancer patients. We did not find significant differences between
      Jena and Halle. 86.7% of all subjects with a homozygote PstI/RsaI genotype also
      carried a homozygote DraI genotype, whereas 5.2% of all subjects with a
      heterozygote PstI/RsaI genotype also carried a heterozygote DraI genotype. The
      heterozygote genotype of PstI/RsaI polymorphism always determines the
      heterozygote genotype of DraI polymorphism. Our results failed to demonstrate any
      differences in the distribution of CYP2E1 polymorphisms between renal
      cell/urothelial cancer patients and controls. CONCLUSION: Summing up, our results
      show that CYP2E1 genotype cannot predict risk for renal cell/urothelial cancer in
      the population from 2 different regions in Germany. The results demonstrate a
      lack of association between CYP2E1 genetic polymorphism and renal cell
      cancer/urothelial cancer.

PMID- 9760006
TI  - Long-term therapy with policosanol improves treadmill exercise-ECG testing
      performance of coronary heart disease patients.
AB  - This study examined the effects of long-term lipid-lowering therapy with
      policosanol on the clinical evolution, and exercise-ECG testing responses of 45
      coronary heart disease (CHD) patients with myocardial ischemia, documented by
      exercise 201T1-myocardial perfusion scintigraphy, in an overall randomized,
      double-blind, placebo-controlled trial, made for different test endpoints.
      Fifteen patients were treated with 5 mg of policosanol twice daily; another 15
      patients were administered the same drug dose plus 125 mg aspirin; and the other
      15 patients received placebo plus equal aspirin dose. They were followed for 20
      months, previous baseline observations, with treadmill exercise-ECG, besides
      serum lipid test. Beneficial changes on proportions among the 2 policosanol
      groups and the placebo group, showed an increment on functional capacity class, a
      decrement on rest and exercise angina, and a significant decrease in cardiac
      events, and in ischemic ST segment response, especially in the policosanol plus
      aspirin group (p = 0.05, X2(2df) = 5.8; p = 0.04, p = 0.02; Fisher). After
      treatment, sets of mean changes revealed an increase on maximum oxygen uptake,
      and a decline on double product simultaneously in both policosanol groups (p < or
      = 0.02, p < or = 0.002; Pillais, Hotellings' T2), while the placebo group was
      impaired. Aerobic functional capacity percent showed an increment in policosanol
      groups (p < or = 0.05, paired T). Lipid levels improved as other endpoints
      already reported. A supposed ergogenic effect of octacosanol, policosanol's main
      active compound, was not detected with this design. These results show that
      policosanol-treated CHD patients improved clinical evolution, and exercise-ECG
      responses, owing to the amelioration of myocardial ischemia, even more when
      administered with aspirin.

PMID- 9760007
TI  - Endosulfan poisoning in Northern India: a report of 18 cases.
AB  - Eighteen cases of endosulfan poisoning by accidental overexposure during spray,
      admitted between October 1995 to September 1997, were observed and analyzed.
      These accounted for approximately one third of the total number of poisoning
      cases admitted in our unit during this period. Nausea, vomiting abdominal
      discomfort, tonic and clonic convulsions, confusion, disorientation, and muscular
      twitchings were cardinal manifestations. None of the patients succumbed to their
      illness. Analysis of various incriminating factors revealed that accidental
      overexposure was due to failure to adhere to the instructions for spray either
      due to ignorance or due to illiteracy. All the patients avoided preventive
      measures and developed toxicity both due to inhalation and absorption through
      skin. Endosulfan (a chlordiene derivative) poisoning is gaining up momentum in
      this part of world and has become an important matter for public health in India.

PMID- 9760008
TI  - Drug-induced admissions to medical wards at Jordan University Hospital.
AB  - The objective of this study was to determine the prevalence of drug-induced
      disease necessitating hospital admission to Jordan University Hospital. This
      study also attempted to identify the most commonly involved drugs as well as the
      vulnerable groups of patients and the potential causes which favor the problem.
      All admissions to Internal Medicine Department were screened for drug-induced
      causality by detailed drug history and appropriate examination. The prevalence
      rate of drug-induced admissions was 3.6%, 52% of them were females. Many of the
      cases were of severe nature. Most of the cases were due to predictable effects of
      the drugs used, which were mainly chemotherapeutic agents. The bone marrow was
      the most affected body organ. Results are in agreement with reports published
      elsewhere and can be explained by the fact that Jordan University Hospital is the
      main teaching hospital in Jordan, has an intermediate location and is a referral
      hospital for oncology-hematology service.

PMID- 9760009
TI  - Influence of captopril, propranolol, and verapamil on arterial pulse wave
      velocity and other cardiovascular parameters in healthy volunteers.
AB  - OBJECTIVE: The effects of antihypertensive agents on cardiovascular parameters,
      especially on arterial pulse wave velocity, remain largely unknown in
      normotensive subjects. Therefore, the present investigation was designed to
      evaluate acute effects of ACE inhibitor captopril,beta-adrenoceptor blocker
      propranolol and calcium entry blocker verapamil on cardiovascular and ventilatory
      function in healthy volunteers. MATERIAL: The influence of single doses of
      captopril (25 mg), propranolol (40 mg), and verapamil (80 mg) on cardiovascular
      function and exercise capacity were compared in healthy volunteers in a
      randomized, double-blind, placebo-controlled fashion. METHODS: Cardiac output and
      beat-by-beat blood pressure were estimated non-invasively before and after the
      drug administrations by whole-body impedance cardiography and Finapres finger
      blood pressure monitoring, respectively. Arterial pulse wave velocity was
      obtained from the time delay between flow pulses measured from the root of the
      aorta and the popliteal artery, and systemic vascular resistance was calculated
      from cardiac output and mean arterial pressure. In addition, a progressive
      maximal exercise test was performed after the treatments. RESULTS: Propranolol
      reduced heart rate, cardiac output and arterial pulse wave velocity, and
      increased systemic vascular resistance clearly more effectively than placebo. In
      addition, captopril effectively decreased arterial resistance and pulse wave
      velocity. However, the influence of verapamil on cardiovascular parameters did
      not significantly differ from those observed in placebo-treated subjects.
      Exercise peak heart rate, peak blood pressure, and minute ventilation were
      reduced in subjects treated with propranolol, but not in those treated with
      captopril and verapamil, when compared to placebo. CONCLUSIONS: Acute
      administration of captopril and propranolol but not verapamil clearly modulated
      cardiovascular parameters in rest, suggesting differential effects of these
      compounds on cardiovascular function in healthy volunteers. These drugs seem to
      have disparate effects on arterial pulse wave propagation as an indicator of
      arterial compliance after short-term administration in healthy subjects.
      Captopril and verapamil had no effect on cardiovascular and ventilatory function
      during maximal exercise, while propranolol markedly altered also these variables
      in the present study.

PMID- 9760010
TI  - Pharmacokinetics of lubeluzole (Prosynap) after single intravenous doses in
      healthy subjects.
AB  - The single-dose pharmacokinetics of lubeluzole were investigated in 2 single
      blind, placebo-controlled, dose-escalation studies in healthy male subjects. In
      the first study, 6 subjects received an intravenous infusion of 2.5, 5, and 10 mg
      lubeluzole. In the second study, a 15 mg dose of lubeluzole was administered to 6
      subjects, of whom 5 also received 20 mg and 2 also 25 mg lubeluzole. Following
      the infusion, plasma lubeluzole concentrations decayed biphasically, with a mean
      distribution half-life (t1/2alpha) of 30 to 65 minutes and a mean terminal half
      life (t1/2beta) of 15 to 24 hours. The results of the 2 studies indicate that
      lubeluzole exhibits linear kinetics over the dose range tested in healthy male
      subjects.

PMID- 9760011
TI  - The duration of antidiuretic response of two desmopressin nasal sprays.
AB  - The duration of antidiuretic response and pharmacokinetics of desmopressin were
      investigated in 16 healthy, male overhydrated volunteers after intranasal
      administration of 20 microg desmopressin (dDAVP). The antidiuretic activity was
      determined by measuring urine osmolality and diuresis over a period of 24 hours.
      Both study preparations were equally effective regarding a rapid onset of
      activity and a highly reproducible extent of effect. Urine osmolalities, analyzed
      as areas under the time curve (AUCosm) were similar for both nasal sprays. Urine
      volumes were comparable. Bioequivalence was assessed for the primary criterion
      AUCosm by a calculated mean ratio (test/reference) of 100.9% (90% confidence
      interval ranging from 88.0% to 115.6%). Plasma levels of desmopressin, measured
      by a specific and sensitive radioimmunoassay method, were already detectable 20
      minutes after administration. The mean time courses showed a similar shape with
      increased concentration levels for the test preparation. Consequently maximum
      desmopressin plasma concentrations were different, showing high interindividual
      variability. However, the times of reaching maximum plasma concentrations were
      similar. AUC(0-24h) was significantly raised after treatment with the test
      preparation (mean ratio of 127.9%; 90% confidence interval ranging from 106.6% to
      153.5%). A subanalysis of the 2 reference batches with the two-sided t-test
      procedure for parallel groups resulted in a mean ratio of 83.1% with a 90%
      confidence interval ranging from 67.2% to 102.7%. The estimated ratios of the 2
      batches of the reference preparation were borderline to the equivalence range. In
      conclusion, both study preparations had the same pronounced biological effect
      with different desmopressin bioavailabilities.

PMID- 9760012
TI  - Effect of fat distribution on the pharmacokinetics of cortisol in obesity.
AB  - OBJECTIVE: Patients with predominantly upper body obesity are at greater risk for
      developing diabetes mellitus, hyperlipidemia, hypertension, and cardiovascular
      disease. Little is known about the mechanisms involved in the regulation of
      regional body distribution. It has been accepted that the accumulation of fat
      into adipose tissue depends on regional metabolic regulation of adipocytes and
      that glucocorticoids play a role in this mechanism. The aim of the present study
      is to investigate how the pharmacokinetics of cortisol correlate to
      intraabdominal and subcutaneous fat distribution in obese patients. METHODS: A
      group of 24 obese patients (13 males and 11 females) were submitted to a CT scan
      for intraabdominal and subcutaneous fat area evaluation. A 30-min cortisol
      infusion (0.25 mg/kg) was administered and plasma cortisol was measured over 6
      hours. RESULTS: Patients with larger intraabdominal fat areas were found to have
      a higher cortisol clearance than those with lower intraabdominal fat areas.
      Cortisol clearance (both, absolute and body-weight corrected) showed a
      statistically significant correlation with intraabdominal fat area, either
      expressed by waist-hip ratio or obtained by computerized tomography. CONCLUSIONS:
      These findings indicate a more effective clearance capability for cortisol in
      patients with central obesity resulting in lowered cortisol plasma levels despite
      an increased cortisol secretion observed in this patient group.

PMID- 9760013
TI  - Plasma coenzyme Q10 concentrations in breast cancer: prognosis and therapeutic
      consequences.
AB  - BACKGROUND: Coenzyme Q10 or ubiquinone is a redox component of the respiratory
      chain, which may be involved in the pathogenesis of cancer. METHODS: In order to
      better understand the role of this vitamin in the pathogenesis of breast cancer,
      a clinical trial including 200 women hospitalized for the biopsy and/or the
      ablation of a breast tumor was conducted. Ubiquinone plasma concentrations were
      determined simultaneously with vitamin E plasma concentrations (as antioxidant
      reference) by HPLC. RESULTS: A coenzyme Q10 deficiency was noted both in
      carcinomas (80 patients) and non-malignant lesions (120 patients), while vitamin
      E concentrations were within the normal range. A correlation was shown between
      the intensity of the deficiency and the bad prognosis of the breast disease based
      on high TNM and SBR values or the lack of estrogen receptors. However, neither
      cathepsin D level nor adenopathy invasion was related to ubiquinone levels.
      CONCLUSIONS: Since prooxidants may promote tumorigenesis, ubiquinone
      supplementation in breast cancer could be relevant.

PMID- 9760016
TI  - Seminal androgen concentrations and residual sperm cytoplasm.
AB  - To explore a possible link between seminal androgen concentrations and residual
      sperm cytoplasm, which constitutes one of the cytological anomalies of the
      spermatozoon middle piece, testosterone (T), delta4-androstenedione, the
      precursor of T during testicular androgen biosynthesis and the active metabolite
      of T, dihydrotestosterone, were assayed in the seminal fluid of 37 patients. A
      statistically significant correlation was found by linear regression (r = +0.380,
      P = 0.020, y = 0.02x + 0.45) between seminal T concentrations and the percentage
      of spermatozoa with a residual cytoplasmic droplet. Given the impact on fertility
      of residual sperm cytoplasm, assessment of seminal T concentrations could provide
      useful information on the fertility status of patients.

PMID- 9760015
TI  - Antioxidant status in hyperphenylalaninemia.
AB  - Abnormal oxidative stress was observed in some inborn errors of metabolism owing
      to the accumulation of toxic metabolites leading to excessive free radical
      production and to the influence of restricted diets on the antioxidant status.
      Erythrocyte antioxidant enzymes activities and tocopherol concentrations were
      measured in a group of phenylketonuric (n = 42) and mild-hyperphenylalaninemic (n
      = 28) patients compared with 45 age-matched controls. We also determined plasma
      selenium levels in these groups. We also evaluated the possible relationship
      between antioxidant status and neuropsychological disorders. Erythrocyte
      glutathione peroxidase (GSH-Px) activity was significantly lower (P < 0.001) in
      both phenylketonuric and mild-hyperphenylalaninemic patients compared with the
      control group, but no differences were observed between the two groups of
      patients. Neuropsychological disturbances were more frequent in the group of PKU
      patients with low GSH-Px activity than in PKU patients with normal GSH-Px. Low
      GSH-Px activity might be explained in phenylketonuria as a result of a selenium
      deficiency caused by a poor selenium intake or absorption, but not in mild
      hyperphenylalaninemic patients with free diet. Selenium levels were normal in
      both groups of patients, so low glutathione peroxidase activity in both
      phenylketonuric and hyperphenylalaninemic groups might be influenced by other
      factors, such as the consequences of an unbalanced amino acid profile, common to
      both conditions.

PMID- 9760014
TI  - Clinical efficacy and safety of beclomethasone dipropionate inhalation capsules
      inhaled by Cyclohaler compared with Becotide Rotacaps inhaled by Rotahaler.
AB  - The study was undertaken to compare the efficacy and safety of beclomethasone
      dipropionate inhalation powder inhaled by Rotahaler (Becotide Rotacaps, Glaxo
      Wellcome) and by Cyclohaler (Beclomethasone Cyclocaps, Pharmachemie). Both the
      Cyclohaler and the Rotahaler are single-dose dry powder inhalation devices for
      inhalation capsules. 182 asthma patients stabilized on inhaled beclomethasone
      dipropionate 800 micrograms daily, were randomly assigned to treatment with 800
      micrograms beclomethasone dipropionate inhaled by Rotahaler (91 patients) or
      Cyclohaler (91 patients) in a double-blind manner, using the double-dummy method.
      It was shown that the asthma remained stable during the 16-week study period with
      both preparations. There were no statistically significant differences in the
      pulmonary parameters (morning PEF, evening PEF, FEV1). The test/reference ratio
      of the morning PEF (99.5%, CI 93.0% - 106.5%) was well within the equivalence
      interval, which had been set a priori from 85% to 117.6%. There were no marked
      differences between the Cyclocaps and Rotacaps group in symptom scores and
      adverse events. A total of 12 patients had an asthma exacerbation: 8
      exacerbations occurred in the Rotahaler group and 4 in the Cyclohaler group. The
      difference was not statistically significant. The use of rescue medication was
      somewhat higher in the Rotahaler group, but the difference did not reach
      statistical significance. Significantly more patients (17 patients) withdrew from
      the study in the Rotahaler group than in the Cyclohaler group (5 patients). In
      conclusion, there was no difference in asthma control of patients treated with
      Beclomethasone Cyclocaps inhaled by Cyclohaler and Becotide Rotacaps inhaled by
      Rotahaler. Both preparations are therapeutically equivalent.

PMID- 9760017
TI  - Determination of serum tetranectin: technical and clinical evaluation of three
      sandwich immunoassays.
AB  - The performance of two sandwich-type immunoassays for the determination of the
      tumour marker tetranectin using monoclonal antibodies Hyb 130-13 and 130-14 as
      catching layer was compared with the performance of a polyclonal assay.
      Sensitivities were 0.4-0.6 microg/l, and intra- and inter-assay coefficients of
      variation were < 10% in all assays. One-hundred-and-ten blood donors were
      examined, and women had higher concentrations of tetranectin in serum than men
      when measured with monoclonal assays (P < 0.05). In preoperative serum samples
      from 43 patients with ovarian cancer, tetranectin concentrations were reduced (P
      < 0.001), and the mean tetranectin concentration decreased with increasing FIGO
      stage of the patients (P < 0.05). In sera from patients with ovarian cancer,
      tetranectin concentrations were lower in the polyclonal assay than in the
      monoclonal assays. This could, hypothetically, be explained by ligand-binding or
      other conformational changes in tetranectin, influencing the antigenicity of the
      molecule.

PMID- 9760018
TI  - Production and certification of an enzyme reference material for creatine kinase
      isoenzyme 2 (CRM 608).
AB  - We describe the preparation of a lyophilized material containing purified human
      creatine kinase 2 (CK-MB), and the certification of its catalytic concentration.
      The material can be used to verify the comparability of results from different
      laboratories, for intra-laboratory quality control, or for calibration of the
      creatine kinase 2 catalytic concentration measurements. The enzyme was purified
      from human heart by ethanol precipitation and chromatography successively on DEAE
      Sephacel and Blue-Sepharose. The purified enzyme had a specific activity of 998.4
      U/mg and was > 99% pure on polyacrylamide gel electrophoresis. The material was
      examined for several possible contaminating enzymes, which were found to be
      absent. The purified creatine kinase 2 had two subunits (B and M) with molecular
      masses of 43,650 and 41,700 g/mol, respectively, and an isoelectric point at pH
      5.8. The material was prepared by diluting the purified creatine kinase 2 in a
      matrix containing 25 mmol/L PIPES buffer, pH 7.2, 2 mmol/L ADP, 5 mmol/L 2
      mercaptoethanol, 154 mmol/L sodium chloride and 50 g/L human serum albumin,
      dispensing it into vials and freeze-drying. The batch was shown to be
      homogeneous. The loss of enzyme activity on storage at -20 degrees C is predicted
      to be less than 0.18% per annum on the basis of accelerated degradation studies.
      The catalytic concentration of creatine kinase in samples of the reconstituted
      material is certified to be 67.2+/-1.8 U/L (1.12+/-0.03 microkat/L) when
      measured, at 30 degrees C, by the Recommended Method of the International
      Federation of Clinical Chemistry.

PMID- 9760019
TI  - Expression and processing of recombinant human galactosylceramidase.
AB  - Stable transformants of CHO cells that overexpress human galactosylceramidase
      (GALC) were established. The GALC within the cell consisted of 50- and 30-kDa
      proteins. The active GALC secreted into the culture medium in large amounts
      consisted of the 80-kDa precursor enzyme. We confirmed that the precursor enzyme
      was taken up by fibroblasts via the mannose-6-phosphate receptor and processed
      into the 50- and 30-kDa fragments. Fragmentation was inhibited by the
      lysosomotropic agents chloroquine and NH4Cl, suggesting that it occurs within the
      lysosome. GALC mutations identified in globoid cell leukodystrophy suppressed
      fragmentation. Neither the 50- or 30-kDa fragment expressed had GALC activity,
      indicative that the entire structure is necessary for enzyme activity and that
      fragments expressed separately cannot associate to form the active enzyme.

PMID- 9760020
TI  - Noninvasive monitoring using serum amyloid A and serum neopterin in cardiac
      transplantation.
AB  - The monitoring of allograft function for cardiac transplant patients still relies
      on endomyocardial routine biopsies. We investigated the diagnostic value of
      noninvasive monitoring using the parameters serum amyloid A protein and serum
      neopterin. The circulating levels of the acute phase reactant, amyloid A protein,
      and the macrophage product, neopterin, were measured serially in 13 patients
      after cardiac transplantation. The mean period of observation was 240 days. Nine
      acute cardiac allograft rejections, five cases of viral infection and eight cases
      of bacterial infection occurred. The levels of serum amyloid A protein and serum
      neopterin remained low (x = 6.0 mg/dL and 12.6 nmol/L, respectively) during the
      periods of stable graft function. In contrast, both parameters were significantly
      elevated (p < 0.01) during the rejection episodes (x = 12.7 mg/dL and 38.0 nmol/L
      for serum amyloid A protein and serum neopterin, respectively). For a reliable
      differentiation between rejection and stable graft function, serum amyloid A
      protein had a diagnostic accuracy of 84% (with a cut-off level of 10 mg/dL) and
      serum neopterin had one of 75% (with a cut-off level of 23 nmol/L). However,
      significant increases in the circulating levels of serum amyloid A protein and
      serum neopterin were also observed during bacterial (x = 14.9 and 88 nmol/L,
      respectively) and viral (x = 6.2 mg/dL and 44 nmol/L, respectively) infections.
      The detection of immunological complications after cardiac transplantation using
      serial measurements of serum amyloid A protein and serum neopterin is possible.
      These parameters can be used to help in judging both the need and the optimal
      timing for the otherwise frequent endomyocardial biopsies.

PMID- 9760021
TI  - The stability of retinol, alpha-tocopherol, trans-lycopene, and trans-beta
      carotene in liquid-frozen and lyophilized serum.
AB  - The concentrations of retinol, alpha-tocopherol, and trans-beta-carotene in
      lyophilized serum stored at -25 degrees C and -80 degrees C have been monitored
      for 10 years. There was no evidence of degradation of any of these compounds over
      the 10-year period. Retinol, alpha-tocopherol, and trans-beta-carotene were less
      stable at -25 degrees C in liquid-frozen serum than they were in lyophilized
      serum. At -80 degrees C, trans-beta-carotene levels were stable for up to 3 years
      of storage in liquid-frozen serum. Both retinol and alpha-tocopherol appeared
      stable in liquid-frozen serum for at least 5 years at -80 degrees C. The effect
      of repeated freeze/thaw cycles on retinol, alpha-tocopherol, trans-lycopene, and
      trans-beta-carotene in liquid-frozen and reconstituted lyophilized serum both
      stored at -20 degrees C was also studied. Retinol, alpha-tocopherol, trans
      lycopene, and trans-beta-carotene in reconstituted lyophilized serum stored at 
      20 degrees C were stable for at least 3 days with minimal (< 5) freeze/thaw
      cycles.

PMID- 9760022
TI  - Simultaneous measurement of catecholamines and kallikrein in urine using boric
      acid preservative.
AB  - Catecholamines, dopamine and the renal kallikrein-kinin system may participate in
      the pathogenesis of hypertension. In the past these systems have been studied
      independently in isolation. Attempts to study the systems together have been
      hampered by incompatibility of the current urine preservatives for the two assays
      involved. In order to measure acid-stable catecholamines and acid-labile
      kallikrein enzyme together, we have established boric acid solution as a
      preservative by comparing the stability of urinary catecholamines stored in it
      with the commonly employed preservative, hydrochloric acid (HCl) as well as the
      stability of urinary kallikrein in untreated urine with and without boric acid at
      ambient temperatures for 24 and 48 h, and at -20 degrees C for 2 weeks and 1, 2
      and 3 months. The stability of other common urine parameters including cortisol,
      electrolytes, creatinine and protein, was also investigated after storage with
      boric acid at ambient temperature for 24 h. Our results showed that there was a
      good agreement between the measurements of urinary catecholamines stored in both
      HCl and boric acid and that the latter did not interfere with measurements of
      urinary kallikrein or other common urine parameters.

PMID- 9760023
TI  - Comparison of indices for serum vitamin E status in healthy subjects.

PMID- 9760024
TI  - Evaluation of cannabimimetic effects of structural analogs of anandamide in rats.
AB  - Arachidonylethanolamide (anandamide), an endogenous ligand for the cannabinoid
      receptor, binds competitively to brain cannabinoid receptors and shares many, but
      not all, of the in vivo effects of delta9-tetrahydrocannabinol. In this study,
      the cannabinoid effects of anandamide analogs in which the anandamide molecule
      was altered were assessed in a drug discrimination model. Structural
      manipulations of the anandamide molecule included saturation of the arachidonyl
      moiety with fluorination (O-586), substitution for either the ethanolamide moiety
      (O-612 and O-595) or C2' hydroxyl (O-585), and addition of a methyl group at
      various positions (O-610, O-680, and O-689). Despite the low binding affinities
      of the non-methylated compounds (Ki values > 2000 nM), all of the analogs had
      previously shown cannabinoid activity in mice. In the present study, these
      analogs were tested in a more pharmacologically specific delta9
      tetrahydrocannabinol discrimination procedure in rats. This animal model is
      predictive of the subjective effects of marijuana intoxication in humans. Whereas
      delta9-tetrahydrocannabinol and an aminoakylindole fully substituted for the
      training dose of 3 mg/kg delta9-tetrahydrocannabinol, anandamide and its non
      methylated analogs were not cannabimimetic in this procedure. Methylation
      appeared to increase binding affinity (Ki values < 150 nM) and efficacy; however,
      the greatest substitution produced by the methylated analogs occurred only at
      doses that decreased overall rates of responding, suggesting that these analogs
      are not fully delta9-tetrahydrocannabinol-like. The rapid metabolism of
      anandamide and some of its analogs undoubtedly contribute to the differences
      between the pharmacological profiles of the anandamides and classical
      cannabinoids. These results support the prediction that the subjective effects of
      anandamide analogs that have been developed thus far would not be cannabimimetic
      except at high doses.

PMID- 9760025
TI  - Cannabinoids decrease acetylcholine release in the medial-prefrontal cortex and
      hippocampus, reversal by SR 141716A.
AB  - The effect of delta9-tetrahydrocannabinol, the psychoactive principle of
      marijuana, and [R-(+)-(2,3-dihydro-5-methyl-3-[[4-morpholinylmethyl]pyrol[1,2,3-d
      e-]-1,4-benzoxazin-6y)(1-naphthalenyl)methanone monomethanesulfonate] (WIN 55,212
      2), a synthetic cannabinoid receptor agonist, on the acetylcholine output in the
      medial-prefrontal cortex and hippocampus was studied by microdialysis in freely
      moving rats. The administration of delta9-tetrahydrocannabinol (1 and 5 mg/kg
      i.p.) and WIN 55,212-2 (5 and 10 mg/kg i.p.) produced a long lasting inhibition
      of acetylcholine release in both areas. The inhibitory effect of delta9
      tetrahydrocannabinol and WIN 55,212-2 was suppressed in both areas by the
      specific cannabinoid CB1 receptor antagonist, [N-(piperidin-1-yl)-5-(4
      chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1H-pyrazole-3carboxamide]HCl (SR
      141716A), at the dose of 0.1 mg/kg i.p., per se ineffective to modify basal
      acetylcholine release. Most interestingly, SR 141716A alone at higher doses
      increased acetylcholine release both in the medial-prefrontal cortex (3 mg/kg
      i.p.) and hippocampus (1 and 3 mg/kg i.p.), suggesting that acetylcholine output
      is tonically inhibited by endogenous cannabinoids. Since the inhibitory effect of
      delta9-tetrahydrocannabinol is produced by doses within those relevant to human
      use of marijuana, our results suggest that the negative effects of the latter on
      cognitive processes may be explained by its ability to reduce acetylcholine
      release in the medial-prefrontal cortex and hippocampus. Conversely, cannabinoid
      receptor antagonists may offer potential treatments for cognitive deficits.

PMID- 9760026
TI  - Effect of losartan on afferent nerve stimulation.
AB  - The present study was undertaken to investigate the effects of losartan, a non
      peptide angiotensin II subtype 1 (AT1) receptor antagonist, on both the pressor
      responses elicited by stimulation of afferent vagal nociceptive fibres and the
      involvement of the sympathetic nervous system (evaluated by plasma levels of
      noradrenaline and its co-neurotransmitter neuropeptide Y) in dogs. Electrical
      stimulation of the afferent fibres of the vagus (1, 5, 10 and 20 Hz) elicited a
      frequency-dependent increase in blood pressure and heart rate. Plasma
      noradrenaline levels only increased after stimulation at frequencies of 10 and 20
      Hz. Plasma neuropeptide Y levels did not change. Losartan (10 mg/kg i.v.) induced
      both a decrease in resting blood pressure and an increase in basal plasma levels
      of noradrenaline and neuropeptide Y. Losartan failed to modify the magnitude of
      the electrically-evoked pressor and positive chronotropic responses. The
      angiotensin AT1 receptor antagonist elicited a fall in plasma noradrenaline
      values after a 1 Hz stimulation and abolished the increase in plasma
      noradrenaline levels induced by the 10 (but not 20) Hz stimulation. The data
      suggest that angiotensin AT1 receptors are not directly involved in acute pressor
      responses induced by stimulation of afferent vagal fibres. Moreover, the results
      show that, besides its sympatho-inhibitory effect, losartan can exert a sympatho
      excitatory action as shown by the increase in the plasma levels of both
      noradrenaline and its coneurotransmitter, neuropeptide Y.

PMID- 9760027
TI  - Acetylsalicylic acid potentiates the antinociceptive effect of morphine in the
      rat: involvement of the central serotonergic system.
AB  - Acetylsalicylic acid and morphine are the most widely distributed and most
      frequently used drugs in the relief of pain, but their analgesic activity has
      adverse side-effects. Mixtures containing these two drugs are frequently used to
      relieve mild to moderate pain despite the paucity of relevant experimental
      evidence so far published. We set out to study the possible antinociceptive
      effect of a combination of subactive doses of the two drugs in rats. A
      combination of low doses of acetylsalicylic acid (50 mg/kg i.p.) and morphine (3
      mg/kg s.c.) was administered and the pain threshold was evaluated in the hot
      plate and formalin tests, and 5-HT2 receptor binding capacity, 5
      hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels were
      measured in the cortex and pontine areas of the brain. The combination of
      acetylsalicylic acid and morphine had an analgesic effect in both tests that was
      associated with an increase in 5-HT levels and a decrease in 5-HT2 receptors in
      the cortex. These effects were either completely abolished or partially prevented
      by i.p. pretreatment with naloxone (1 mg/kg i.p.). Our results demonstrate that
      subactive doses of acetylsalicylic acid and morphine can exert analgesic and
      biochemical effects when given in combination in the rat and suggest an
      involvement of serotonergic and opiatergic systems.

PMID- 9760028
TI  - Opposing roles for dopamine D1 and D2 receptors in the regulation of hypothalamic
      tuberoinfundibular dopamine neurons.
AB  - The purpose of the present study was to characterize pharmacologically dopamine
      D1 receptor-mediated inhibition of tuberoinfundibular dopamine neurons in males
      rats, and to determine if inhibitory dopamine D1 receptors oppose stimulatory
      dopamine D2 receptors and account for the inability of mixed dopamine receptor
      agonists to alter the activity of these neurons. Tuberoinfundibular dopamine
      neuronal activity was estimated by measuring the concentrations of the dopamine
      metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the median eminence, the
      region of the hypothalamus containing terminals of these neurons. Administration
      of the dopamine D1 receptor agonist (+/-)-1 phenyl-2,3,4,5-tetrahydro-(1 H)-3
      benzazepine-7,8-diol (SKF38393) decreased median eminence DOPAC and increased
      plasma prolactin concentrations, whereas administration of the dopamine D1
      receptor antagonist ((-)-trans,6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N
      methyl-5H -benzo[d]naphtho-[2,1 b]azepine (SCH39166) increased median eminence
      DOPAC concentrations but had not effect on plasma prolactin. The inhibitory
      effect of SKF38393 on median eminence DOPAC concentrations was blocked by
      SCH39166. These results demonstrate that acute activation of dopamine D1
      receptors inhibits the activity of tuberoinfundibular dopamine neurons and
      thereby increases prolactin secretion, and that under basal conditions dopamine
      D1 receptor-mediated inhibition of tuberoinfundibular dopamine neurons is
      tonically active. Administration of the dopamine D2 receptor agonist (5aR-trans)
      5,5a,6,7,8,9,9a,10-octahydro-6-propyl-pyridol[2, 3-g]quinazolin-2-amine
      (quinelorane) increased median eminence DOPAC concentrations, and SKF38393 caused
      a dose-dependent reversal of this effect. Administration of the mixed dopamine
      D1/D2 receptor agonist R(-)-10,11-dihydroxy-apomorphine (apomorphine) had no
      effect per se, but blocked quinelorane-induced increases in DOPAC concentrations
      in the median eminence. These results reveal that concurrent activation of
      dopamine D1 and D2 receptors nullifies the actions of each of these receptors on
      tuberoinfundibular dopamine neurons, which likely accounts for the lack of an
      acute effect of mixed dopamine D1/D2 receptor agonists on these hypothalamic
      dopamine neurons.

PMID- 9760029
TI  - The difference in the inhibitory mechanisms of papaverine on vascular and
      intestinal smooth muscles.
AB  - Papaverine (0.3-100 microM) more potently inhibited phenylephrine (1 microM)
      induced contraction than 65 mM K+-induced contraction of the aorta, while it
      equally inhibited contractions induced by 65 mM K+ and carbachol (1 microM) in
      ileal smooth muscle. In phenylephrine-treated aorta, papaverine (1-10 microM)
      increased the cAMP and cGMP content. However, in carbachol-treated ileum, 30
      microM papaverine partially increased the cAMP content while it maximally relaxed
      the preparation. In fura2-loaded aorta, papaverine (0.3-10 microM) inhibited both
      the contraction and the increase in intracellular Ca2+ level ([Ca2+]i) induced by
      phenylephrine in parallel. However, papaverine inhibited carbachol-induced
      contraction with only a small decrease in [Ca2+]i. Papaverine (1-30 microM)
      inhibited the carbachol-induced increase in oxidized flavoproteins, an indicator
      of increased mitochondrial oxidative phosphorylation, in ileal smooth muscle
      whereas it did not change the phenylephrine-induced increase in the aorta. These
      results suggest that papaverine inhibits smooth muscle contraction mainly by the
      accumulation of cAMP and/or cGMP due to the inhibition of phosphodiesterase in
      the aorta whereas, in ileal smooth muscle, papaverine inhibits smooth muscle
      contraction mainly by the inhibition of mitochondrial respiration.

PMID- 9760030
TI  - Effects of the optical isomers of verapamil on electrophysiological properties of
      the heart in conscious dogs.
AB  - We compared the cumulative dose-response relations of verapamil (0.1, 0.2 and 0.4
      mg kg(-1)) in different R/S enantiomer ratios (100/0, 90/10, 80/20, 50/50 and
      20/80) on the electrophysiological and hemodynamic characteristics of the heart
      using the conscious dogs. A reduction of mean arterial pressure occurred with
      20R/80S producing a 3-times greater decrease than 100R/0S, but an increase in
      heart rate occurred with 20R/80S producing a 9-times greater increase than
      100R/0S. Increased heart rate was concurrent with decreased mean arterial
      pressure most prevalent with a higher ratio of S-isomer that produced a greater
      reduction in mean arterial pressure and increase in heart rate at lower overall
      verapamil doses. Atrio-ventricular conduction time increased 3-5 min after each
      infusion, with 20R/80S producing a 4-times greater effect than 100R/0S. These
      results indicate that the peripheral and cardiac electrophysiologic properties of
      various nonracemic verapamil mixtures are mainly attributable to the
      concentration of S-isomer.

PMID- 9760031
TI  - Impaired endothelium-dependent relaxation in large, but not small arteries in
      rats after coronary ligation.
AB  - Vascular responses were studied in both large and small arteries of rats
      following 8 weeks of heart failure produced by coronary ligation. Responses to
      noradrenaline, acetylcholine and sodium nitroprusside were studied in isolated
      thoracic aorta and mesenteric arteries. In the aorta, concentration-response
      curves for noradrenaline were similar between heart failure and sham animals and
      unaffected by the nitric oxide synthase inhibitor, NG-nitro-L-arginine (L-NOARG).
      Relaxation by acetylcholine was impaired in heart failure rats (EC50-6.79 log M
      heart failure vs. -7.15 log M sham). In the presence of L-NOARG, relaxation by
      acetylcholine was completely abolished in rings from sham rats, whereas
      constriction was observed in rings from heart failure rats. Relaxation by sodium
      nitroprusside was not different between sham and heart failure rats. In
      mesenteric arteries, responses to noradrenaline, acetylcholine and sodium
      nitroprusside were not different between heart failure and sham rats. L-NOARG
      reduced the maximum response to acetylcholine in both heart failure (82% to 50%)
      and shams (89% to 49%) by a similar magnitude, with no effect on relaxation to
      sodium nitroprusside. These data suggest that acetylcholine-induced relaxation is
      impaired in the aorta, but not mesenteric arteries in rats with heart failure.
      The mechanism is not solely due to impaired nitric oxide release and may be due
      to acetylcholine-induced contraction.

PMID- 9760032
TI  - Evidence for different 5-HT1B/1D receptors mediating vasoconstriction of equine
      digital arteries and veins.
AB  - 5-hydroxytryptamine (5-HT) is a potent vasoconstrictor of equine digital arteries
      and veins which may play a role in the ischaemic disease, laminitis. The present
      investigation compared the properties of 5-HT1B/1D receptors in arteries with
      those in veins using isolated rings of equine digital blood vessels. The 5
      HT1B/1D receptor-selective agonists, anpirtoline and sumatriptan were 17.9 and 10
      times more potent and produced 4.1 and 5.6 times greater maximum contractions,
      respectively, in veins when compared to arteries. Other agonists tested were of
      equal potency and produced the same maximum responses in veins and arteries.
      Propranolol competitively inhibited 5-HT1B/1D receptor mediated responses in
      arteries, with a pKB of 6.7, but had no significant effects on responses in veins
      at 1 microM. Metergoline competitively inhibited 5-HT1B/1D receptor mediated
      responses in veins, with a pKB of 8.1, but had no significant effect in arteries
      at 0.1 microM. These data suggest that 5-HT1B/1D receptors mediating
      vasoconstriction in equine digital arteries are pharmacologically different to
      those found in digital veins.

PMID- 9760034
TI  - A comparison of the effects of capsaicin with inhibitory nerve stimulation in the
      rat anococcygeus muscle in vitro.
AB  - Capsaicin was used to test whether centrifugal activation of sensory fibres in
      the rat anococcygeus muscle can contribute to non-adrenergic non-cholinergic
      (NANC) relaxation of the muscle. In a solution containing 0.5 mM Ca2+ and in the
      presence of carbachol (10 microM) capsaicin evoked a fast concentration-dependent
      relaxation of the muscle that was usually followed by a smaller, slower, relaxant
      response. The fast relaxant response was reduced when extracellular Ca2+ was
      raised to 2.5 mM, desensitized after a single application of capsaicin and was
      blocked by tetrodotoxin (1 microM) or ruthenium red (10 microM). The fast
      response was greatly reduced by haemoglobin, by cold storage of the muscles or by
      N-monomethyl-L-arginine (100 microM) in the absence but not in the presence of L
      arginine (100 microM). It is concluded that centrifugal activation of sensory
      fibres evokes a nitric oxide-mediated relaxation of the anococcygeus muscles that
      probably contributes to electrically evoked NANC relaxation.

PMID- 9760033
TI  - Blockade of beta-adrenoceptors enhances cAMP signal transduction in vivo.
AB  - The aim of this study was to determine whether the blockade of beta-adrenoceptors
      would enhance cAMP-mediated signal transduction processes in vivo. The
      administration of the membrane permeable cAMP analogue, 8-(4-chlorophenylthiol)
      cAMP (8-CPT-cAMP, 10 micromol/kg, i.v.) produced an increase in heart rate (+27
      +/- 2%, P < 0.05), a fall in mean arterial blood pressure (-21 +/- 3%, P < 0.05)
      and falls in hindquarter (-12 +/- 3%, P < 0.05) and mesenteric (-32 +/- 3%, P <
      0.05) vascular resistances in pentobarbital-anesthetized rats. The beta
      adrenoceptor antagonist, propranolol (1 mg/kg, i.v.) lowered heart rate (-12 +/-
      3%, P < 0.05) but did not affect mean arterial blood pressure or vascular
      resistances. The tachycardia, hypotension and vasodilation produced by 8-CPT-cAMP
      were exaggerated after administration of propranolol (P < 0.05 for all
      comparisons). The nitric oxide-donor, sodium nitroprusside (2 microg/kg, i.v.),
      produced falls in mean arterial blood pressure and vascular resistances of
      similar magnitude to those produced by 8-CPT-cAMP. These sodium nitroprusside
      induced responses were unaffected by propranolol (P < 0.05 for all comparisons).
      Sodium nitroprusside also produced a minor increase in heart rate (+5 +/- 1%, P <
      0.05) which was abolished by propranolol. These findings suggest that 8-CPT-cAMP
      directly increases heart rate and that blockade of beta-adrenoceptors enhances
      the potency of cAMP within the heart and vasculature.

PMID- 9760035
TI  - Oxytocin receptor binding and uterotonic activity of carbetocin and its
      metabolites following enzymatic degradation.
AB  - Metabolites of the analogue 1-deamino-1-carba-2-tyrosine(O-methyl)-oxytocin
      (carbetocin) following incubation with a rat kidney homogenate were isolated and
      their pharmacodynamic properties investigated. Apart from the parent compound two
      metabolites were identified namely desGlyNH2-carbetocin (carbetocin metabolite I)
      and desLeuGlyNH2-carbetocin (carbetocin metabolite II). Both carbetocin,
      carbetocin metabolite I and carbetocin metabolite II displayed binding affinities
      to the myometrial oxytocin receptor of a similar magnitude as oxytocin.
      Carbetocin was found to have agonistic properties on isolated myometrial strips
      and it was found to exert this effect through generation of inositol phosphates,
      as is the case for oxytocin. However, maximal contractile effect of carbetocin
      was approximately 50% lower than that of oxytocin (2.70 +/- 0.12 g compared to
      5.22 +/- 0.26 g) and EC50 was approximately ten times higher (48.0 +/- 8.20 nM
      compared to 5.62 +/- 1.22 nM). Neither carbetocin metabolite I nor carbetocin
      metabolite II were able to contract isolated myometrial tissue. All three
      compounds displayed antagonistic properties against oxytocin in vitro, with
      carbetocin being the strongest inhibitor (pA2 = 8.21) and carbetocin metabolite
      II (pA2 = 8.01) being stronger than carbetocin metabolite I (pA2 = 7.81). These
      results indicate that carbetocin is a partial agonist/antagonist to the oxytocin
      receptor while the two metabolites carbetocin metabolite I and carbetocin
      metabolite II are pure antagonists. All three analogues bound to the myometrial
      vasopressin V1 receptor, albeit with much lower affinities than to the oxytocin
      receptor. Carbetocin metabolite II showed the weakest binding affinity of 33.7 +/
      7.34 nM compared to 7.24 +/- 0.29 nM for carbetocin and 9.89 + 2.80 nM for
      carbetocin metabolite I. Only carbetocin bound to the renal vasopressin V2
      receptor though the binding affinity was very low (61.3 +/- 14.6 nM).

PMID- 9760036
TI  - Differential effects of inhibitors of cyclooxygenase (cyclooxygenase 1 and
      cyclooxygenase 2) in acute inflammation.
AB  - The anti-inflammatory activity of drugs more selective for cyclooxgenase isoform
      inhibition (cyclooxygenase 1, cyclooxygenase 2), were compared in rat carrageenin
      induced pleurisy. Suppression of inflammation by cyclooxygenase 2-selective
      inhibitors, NS-398 (N-[-2-cyclohexyloxy]-4-nitrophenyl methanesulphonamide) and
      nimesulide (4-nitro-2-phenoxy-methanesulfonanilide), and by piroxicam and
      aspirin, more selective for cyclooxygenase 1, was measured. Piroxicam and aspirin
      significantly inhibited inflammatory cell influx, exudate and prostaglandin E2
      formation, 6 h after carrageenin injection. Cyclooxygenase 2 inhibitors had
      little effect on these parameters with NS-398 alone reducing prostaglandin E2
      levels, but increasing levels of leukotriene B4. In contrast, at 3 h after
      carrageenin injection, cyclooxygenase 2 inhibitors significantly inhibited all
      inflammatory parameters however suppression with piroxicam and aspirin was
      greater, and more pronounced than at 6 h. NS-398 and nimesulide dosing did not
      reduce thromboxane B2 production from platelets isolated from rats with
      carrageenin-induced pleurisy, demonstrating that at the doses used,
      cyclooxygenase 2 inhibitors did not inhibit cyclooxygenase 1, as platelets
      contain only this isoform. Therefore, in the rat carrageenin-induced pleurisy,
      drugs more selective for the inhibition of cyclooxygenase 1 attenuate
      inflammation over a wider time frame than cyclooxygenase 2-selective drugs,
      suggesting a significant role for cyclooxygenase 1 in this model. Inhibition of
      cyclooxygenase 2 by NS-398 however, resulted in an increase in the potent
      chemoattractant leukotriene B4.

PMID- 9760037
TI  - Bradykinin-evoked Ca2+ mobilization in Madin Darby canine kidney cells.
AB  - We studied the mechanisms underlying the bradykinin-evoked changes in
      intracellular calcium concentration ([Ca2+]i) in Madin Darby canine kidney (MDCK)
      cells. Bradykinin evoked a [Ca2+]i transient in a dose-dependent manner, measured
      by fura-2 fluorimetry and digital video imaging. The transient consisted of a
      rise and a decay and [Ca2+]i returned to baseline without oscillations. External
      Ca2+ influx occurred, as demonstrated by Mn2+ quench and external Ca2+ removal
      measurements. Bradykinin acted by stimulating bradykinin B2 receptors as
      evidenced by blockade by D-arginyl-L-arginlyl-L-prolyl-trans-4-hydroxy-L
      prolylglycyl -3-(2-thienyl)-L-alanyl-L-seryl-D-1,2,3,4-tetrahydro-3
      isoquinolineca rbonyl-L-(2alpha,3beta,7alphabeta)-octahydro-1 H-indole-2-carbonyl
      L-arginine (HOE 140) but not by D-arginyl-L-arginlyl-L-prolyl-trans-4-hydroxy-L
      proylglycyl- 3-(2-thienyl)-L-alanyl-L-seryl-D-1,2,3,4-tetrahydro-3
      isoquinolinecar bonyl-L-(2alpha,3beta,7alphabeta)-octahydro-1 H-indole-2-carbonyl
      ([Des-Arg]HOE 140). The [Ca2+]i signal was abolished by 1-(6-((17beta-3
      methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1 H-pyrrole-2,5-dione (U73122)
      and partially inhibited by neomycin, implying mediation by phospholipase C. The
      transient was initiated by a release of Ca2+ from internal stores since it was
      abolished by pretreatment with thapsigargin or cyclopiazonic acid. The
      mobilization of the internal Ca2+ store subsequently triggered a 1-[beta-[3-(4
      methoxyphenyl)propoxy]-4-methoxyphenethyl]-1 H-imidazole hydrochloride (SKF
      96365)-insensitive Ca2+ entry. Pretreatment with carbonylcyanide m
      chlorophynylhydrozone and gly-phe-beta-naphthylamide did not alter the transient,
      thus excluding the participation of mitochondria and lysosomes. Efflux via Ca2+
      pumps contributed to the decay of the transient. Efflux via Na+/Ca2+ exchange or
      sequestration by mitochondria and lysosomes was insignificant. The transient was
      blunted by the protein kinase C activator phorbol 12-myristate 13-acetate, and
      was enhanced by the protein kinase C inhibitors sphingosine and chelerythrine,
      the protein kinase A inhibitor 2,5-di-(t-butyl)-1,4-hydroquinone, N-[2-(p
      bromocinnamylamino)ethyl]5-isoquinolinesulfonamide (H-89), the agent 8
      (diethylamino)octyl 3,4,5-trimethoxybenzoate (TMB-8), and agents that elevated
      levels of 3',5'-cyclic guanosine monophosphate. The transient did not
      heterologously desensitize with that evoked by ATP, ADP or UTP.

PMID- 9760038
TI  - Tenidap enhances P2Z/P2X7 receptor signalling in macrophages.
AB  - Tenidap is an anti-inflammatory drug whose mechanism of action is not fully
      understood. It has been shown to block plasma membrane anion transport and to
      decrease release of interleukin-1beta, probably via the inhibition of interleukin
      1beta converting enzyme. In the present study we showed that: (a) tenidap
      increases the sensitivity of mouse macrophages to cytotoxic effects mediated by
      extracellular ATP; (b) tenidap increases lucifer yellow uptake through the
      macrophage ATP receptor; (c) pretreatment with oxidised ATP, a blocker of the
      P2Z/P2X7 receptor, inhibits cytotoxicity and lucifer yellow uptake due to the
      combined effects of ATP and tenidap; (d) macrophages lacking the P2Z/P2X7
      receptor are resistant to the synergistic effect of tenidap and ATP. The results
      suggest that tenidap synergises with extracellular ATP for activation of the
      P2Z/P2X7 receptor.

PMID- 9760039
TI  - Agonist and antagonist actions of antipsychotic agents at 5-HT1A receptors: a
      [35S]GTPgammaS binding study.
AB  - Recombinant human (h) 5-HT1A receptor-mediated G-protein activation was
      characterised in membranes of transfected Chinese hamster ovary (CHO) cells by
      use of guanosine-5'-O-(3-[35S]thio)-triphosphate ([35S]GTPgammaS binding). The
      potency and efficacy of 21 5-HT receptor agonists and antagonists was determined.
      The agonists, 5-CT (carboxamidotryptamine) and flesinoxan displayed high affinity
      (subnanomolar Ki values) and high efficacy (Emax > 90%, relative to 5-HT = 100%).
      In contrast, ipsapirone, zalospirone and buspirone displayed partial agonist
      activity. EC50s for agonist stimulation of [35S]GTPgammaS binding correlated well
      with Ki values from competition binding (r = +0.99). Among the compounds tested
      for antagonist activity, methiothepin and (+)butaclamol exhibited 'inverse
      agonist' behaviour, inhibiting basal [35S]GTPgammaS binding. The actions of 17
      antipsychotic agents were investigated. Clozapine and several putatively
      'atypical' antipsychotic agents, including ziprasidone, quetiapine and
      tiospirone, exhibited partial agonist activity and marked affinity at h5-HT1A
      receptors, similar to their affinity at hD2 dopamine receptors. In contrast,
      risperidone and sertindole displayed low affinity at h5-HT1A receptors and
      behaved as 'neutral' antagonists, inhibiting 5-HT-stimulated [35S]GTPgammaS
      binding. Likewise the 'typical' neuroleptics, haloperidol, pimozide, raclopride
      and chlorpromazine exhibited relatively low affinity and 'neutral' antagonist
      activity at h5-HT1A receptors with Ki values which correlated with their
      respective Kb values. The present data show that (i) [35S]GTPgammaS binding is an
      effective method to evaluate the efficacy and potency of agonists and antagonists
      at recombinant human 5-HT1A receptors. (ii) Like clozapine, several putatively
      'atypical' antipsychotic drugs display balanced serotonin h5-HT1A/dopamine hD2
      receptor affinity and partial agonist activity at h5-HT1A receptors. (iii)
      Several 'typical' and some putatively 'atypical' antipsychotic agents displayed
      antagonist properties at h5-HT1A sites with generally much lower affinity than at
      hD2 dopamine receptors. It is suggested that agonist activity at 5-HT1A receptors
      may be of utility for certain antipsychotic agents.

PMID- 9760040
TI  - Omega-3 polyunsaturated fatty acids--modulation of voltage-dependent L-type Ca2+
      current in guinea-pig tracheal smooth muscle cells.
AB  - Omega-3 polyunsaturated fatty acids have been reported to be associated with
      favorable changes in the respiratory system. To determine one of the mechanisms
      for this effect, membrane currents were recorded in guinea-pig tracheal myocytes
      by using the whole-cell voltage clamp technique. Without EGTA in the patch
      pipette containing the Cs-internal solution, command voltage pulses positive to
      +0 mV from a holding potential of -60 mV elicited a voltage-dependent L-type Ca2+
      current (I(Ca x L)) and a subsequent outward current. Upon repolarization, slowly
      decaying inward tail currents were recorded. The outward currents and the inward
      tail current were enhanced by methyl-1,4,-dihydro-2,6-dimethyl-3-nitro-4-(2
      trigluromethylphenyl )-pyridine-5-carboxylate, and blocked by Cd2+ or nifedipine.
      Inclusion of EGTA (5 mM) in the patch pipette also abolished these currents,
      indicating that they were Ca2+-dependent. When [Cl-]o or [Cl-]i was changed, the
      reversal potential of these currents shifted, thus behaving like a Cl(-)
      sensitive ion channel. 4,4'-Diisothiocyanatostilbene-2,2'-disulphonic acid. a Cl-
      channel blocker, inhibited the currents. The omega-3 polyunsaturated fatty acids
      eicosapentaenoic acid (3-30 microM) and docosahexaenoic acid (30 microM)
      suppressed I(Ca x L) and then inhibited I(Ca x Cl) in a reversible manner.
      Similar inhibitory effects of eicosapentaenoic acid on I(Ca x L) were observed
      with 5 mM EGTA in the patch pipette. Neurokinin A (1 microM) and caffeine (10 mM)
      also transiently activated I(Cl x Ca), probably due to Ca2+ release from Ca2+
      storage sites. Pretreatment of the cells with eicosapentaenoic acid markedly
      suppressed the activation of I(Cl x Ca) by neurokinin A or caffeine. These
      results suggest that omega-3 polyunsaturated fatty acids inhibit voltage
      dependent L-type Ca2+ currents and also Ca2+-activated Cl- currents in tracheal
      smooth muscle cells from the guinea-pig, which may play a role in modulation of
      tracheal smooth muscle tone.

PMID- 9760041
TI  - Antagonist binding profile of the split chimeric muscarinic m2-trunc/m3-tail
      receptor.
AB  - Recent evidence suggests that G-protein-coupled receptors can behave as multiple
      subunit receptors, and can be split into parts, maintaining their binding
      ability. Transfection of a truncated muscarinic m2 receptor (containing
      transmembrane domains I-V, named m2-trunc) with a gene fragment coding for the
      carboxyl-terminal receptor portion of the muscarinic m3 receptor (containing
      transmembrane domains VI and VII, named m3-tail) results in the formation of a
      binding site with a high affinity for the muscarinic ligand N
      [3H]methylscopolamine. In this paper we analyse the antagonist binding profile of
      this chimeric m2-trunc/m3-tail receptor in comparison with the wild-type
      muscarinic m2 and m3 receptors. While many of the substances tested had an
      intermediate affinity for the chimeric m2-trunc/m3-tail receptor compared with m2
      and m3, some compounds were able to distinguish between the chimeric m2-trunc/m3
      tail receptor on the one hand and the m2 or the m3 receptor on the other. Among
      them, tripitramine (a high-affinity M2 receptor antagonist) bound to the m2
      trunc/m3-tail receptor with the same affinity as m2, but it bound to the m3
      receptor with a 103-fold lower affinity; pirenzepine (a selective muscarinic M1
      receptor antagonist) bound to the chimeric receptor with an affinity that was 12-
      and 3-fold higher than that of m2 and m3, respectively. The results of this study
      demonstrate that the chimeric m2-trunc/m3-tail receptor has a pharmacological
      profile distinct from that of the originating muscarinic m2 and m3 receptors.

PMID- 9760042
TI  - Subtype-specific stimulation of [35S]GTPgammaS binding by recombinant alpha2
      adrenoceptors.
AB  - We measured agonist-stimulated binding of the stable GTP-analog guanosine-5'-O-(3
      [35S]thiotriphosphate) ([35S]GTPgammaS) as a functional assay to monitor G
      protein activation by recombinant human alpha2-adrenoceptor subtypes alpha2A,
      alpha2B and alpha2C. (-)-Noradrenaline was a full agonist in all receptors.
      Dexmedetomidine, UK14,304, clonidine and oxymetazoline showed subtype-selectivity
      in efficacy. Dexmedetomidine was a full agonist at alpha2B and a partial agonist
      at alpha2A; UK14,304 was a full agonist at alpha2A and a partial agonist at
      alpha2B. Clonidine and oxymetazoline were weak partial agonists at the alpha2B
      subtype, but appeared inactive at alpha2A and alpha2C. The [35S]GTPgammaS binding
      assay provides functional information on pertussis toxin-sensitive G-protein
      activation, complementing radioligand binding assays and conventional second
      messenger assays.

PMID- 9760043
TI  - Nitric oxide modulates sympathetic control of left ventricular contraction in
      vivo in the dog.
AB  - Recently, evidence has been presented that nitric oxide (NO) modulates myocardial
      contraction induced by beta-adrenergic stimulation in vitro and in vivo. In this
      study, we investigated whether inhibition of the L-arginine NO system augments
      the positive inotropic response of the left ventricle to direct stimulation of
      the sympathetic nerves in vivo in the dog. Electrical stimulation was applied to
      the left stellate ganglion (LSG) for 1 min at submaximal (5 V, 2.5, 5 and 10 Hz)
      and supramaximal intensities (10 V, 10 Hz) in twelve anesthetized and vagotomized
      dogs. Next, in the same dogs, N(omega)-nitro L-arginine methylester (L-NAME) was
      infused into the left anterior descending (LAD) coronary artery, and LSG
      stimulation repeated using the same protocol. Finally, L-arginine was infused
      into the LAD artery, and LSG stimulation repeated. We used the maximum of the
      first derivative of left ventricular pressure (LV max d P/dt) as an index of the
      myocardial contractility. Plasma epinephrine and norepinephrine concentrations
      were measured in the coronary sinus at 5 V, 2.5 Hz before and after L-NAME
      treatment in five of twelve dogs. L-NAME treatment significantly augmented the
      inotropic response of the left ventricle (percent change in the LV max dP/dt) to
      LSG submaximal stimulation trains from 164 +/- 13 to.212 +/- 21 (P < 0.03), from
      187 +/- 15 to 234 +/- 25 (P < 0.05) and from 220 +/- 19 to 280 +/- 33% (P <
      0.05), respectively. This response was reversed by L-arginine treatment. However,
      the inotropic response to the supramaximal stimulation train did not change after
      L-NAME and L-arginine treatment. L-NAME significantly increased plasma
      norepinephrine concentration from 0.69 +/- 0.41 to 1.00 +/- 0.52 ng/ml without
      changing plasma epinephrine concentration in the coronary sinus. It is concluded
      that the inhibition of the L-arginine NO system augmented the positive inotropic
      effect on the left ventricle during sympathetic nerve stimulation in normal dogs
      in vivo.

PMID- 9760044
TI  - Cholinesterases in cardiac ganglia and modulation of canine intrinsic cardiac
      neuronal activity.
AB  - Cholinergic neurotransmission plays a significant role in intrinsic cardiac
      ganglia with the action of acetylcholine being terminated by acetylcholinesterase
      (AChE, EC 3.1.1.7). Anatomical studies were performed to characterize neurons
      associated with AChE and a closely related enzyme, butyrylcholinesterase (BuChE,
      EC 3.1.1.8), in canine intrinsic cardiac ganglia. Histochemical staining for AChE
      and BuChE in canine right atrial neurons showed that there were four neuronal
      populations, namely, those that contained AChE only, BuChE only, both AChE and
      BuChE, and those that did not contain either enzymes. The neuronal activity of
      intrinsic cardiac neurons in response to substrates and inhibitors of
      cholinesterases were studied in anesthetized dogs. The activity of intrinsic
      cardiac neurons, as measured by changes in the number of action potentials,
      increased by local application of acetylcholine. However, local application of
      butyrylcholine led to a considerably greater increase in the activity of
      intrinsic cardiac neurons. In keeping with the neurochemical heterogeneity in
      intrinsic cardiac ganglia with respect to cholinesterases, the activity generated
      by most butyrylcholine-sensitive neurons was not influenced by acetylcholine and
      the activity generated by the most acetylcholine-sensitive neurons was not
      influenced by butyrylcholine. This suggests that these two agents preferentially
      influence different populations of intrinsic cardiac neurons. Enzyme kinetic
      studies demonstrated that canine AChE preferentially catalyzed the hydrolysis of
      acetylcholine while canine BuChE preferentially catalyzed the hydrolysis of
      butyrylcholine. Cholinesterase inhibitors Ro 2-1250 and Ro 2-0638 inhibited both
      canine cholinesterases, while huperzine A preferentially inhibited canine AChE
      and ethopropazine inhibited canine BuChE. The activity of neurons in the
      intrinsic cardiac ganglia significantly increased when Ro 2-1250 or Ro 2-0638 was
      administered locally. The activity of neurons was not affected when huperzine A
      or ethopropazine was administered, indicating that both cholinesterases must be
      inhibited to increase neuronal activity. In summary, these data show that in
      addition to AChE, intrinsic cardiac ganglia also contain distinct populations of
      neurons that are associated with BuChE, and the activity generated by these
      neurons is differentially influenced by their substrates. Because simultaneous
      inhibition of AChE and BuChE leads to increased neuronal activity, it is
      concluded that AChE- and BuChE-positive intrinsic cardiac neurons may act
      synergistically to influence the overall tonic activity of intrinsic cardiac
      ganglia.

PMID- 9760045
TI  - Antagonist precipitated clonidine withdrawal in rat: effects on locus coeruleus
      neurons, sympathetic nerves and cardiovascular parameters.
AB  - The goal of the present study was to examine the effect of clonidine withdrawal
      on the neural control of blood pressure. Rats were treated for 7-13 days with
      clonidine via osmotic minipumps (200 microg kg(-1) day(-1), s.c.). Controls
      received saline or were sham operated. Withdrawal was precipitated by the alpha2
      adrenergic receptor (alpha2-AR) antagonist atipamezole. Most experiments were
      done under halothane anesthesia. Chronic treatment with clonidine did not change
      mean arterial pressure (MAP) or heart rate (HR) but raised femoral artery
      resistance and the activity of locus coeruleus neurons slightly. Atipamezole
      given to rats treated chronically with clonidine produced the following effects:
      no change in MAP, severe tachycardia, sustained increase in splanchnic
      sympathetic nerve discharge (SND; +75 +/- 13%), transient increase in lumbar SND
      (+23 +/- 7%), ON-OFF activity pattern in the locus coeruleus (LC). The ON phase
      of LC activity was synchronized with upswings of SND and with small changes in
      MAP. A second alpha2-AR antagonist, methoxyidazoxan, produced effects identical
      to those of atipamezole. Atipamezole given to control rats produced no effect on
      MAP, HR, SND or LC activity. Atipamezole reversed the hypotension,
      sympathoinhibition and bradycardia produced by acute administration of clonidine.
      In awake rats treated chronically with clonidine, atipamezole did not change MAP
      but produced arterial pressure lability and tachycardia. In conclusion, under
      anesthesia, selective alpha2-AR antagonists elicit a clonidine withdrawal
      syndrome that displays autonomic characteristics reminiscent of the spontaneous
      withdrawal syndrome found in awake rats. The most prominent features of this
      syndrome are tachycardia, sympathoactivation, lack of hypertension and an
      oscillating activity pattern of brainstem neurons leading to abrupt changes in
      SND and in MAP.

PMID- 9760046
TI  - GABA- and glutamate-immunoreactive synapses on sympathetic preganglionic neurons
      projecting to the superior cervical ganglion.
AB  - Our previous work suggests that virtually all of the synapses on sympathetic
      preganglionic neurons projecting to the rat adrenal medulla are immunoreactive
      for either the inhibitory amino acid, gamma-aminobutyric acid (GABA) or the
      excitatory amino acid, L-glutamate. To investigate whether or not this is true
      for other groups of sympathetic preganglionic neurons, and to determine whether
      or not the proportion of inputs containing each type of amino acid
      neurotransmitter is the same for different groups of sympathetic preganglionic
      neurons, we retrogradely labelled rat and rabbit sympathetic preganglionic
      neurons projecting to the superior cervical ganglion and used post-embedding
      immunogold on ultrathin sections to localise GABA- and glutamate
      immunoreactivity. The cell bodies and dendrites of both rat and rabbit
      sympathetic preganglionic neurons projecting to the superior cervical ganglion
      received synapses and direct contacts from nerve fibres immunoreactive for GABA
      and from nerve fibres immunoreactive for glutamate. In the rat, GABA was present
      in 48.9% of the inputs to sympathetic preganglionic neurons projecting to the
      superior cervical ganglion, and glutamate was present in 51.7% of inputs. Double
      immunogold labelling for glutamate and GABA on the same section, as well as
      labelling of consecutive serial sections for the two antigens, indicated that
      GABA and glutamate occur in separate populations of nerve fibres that provide
      input to rat sympathetic preganglionic neurons projecting to the superior
      cervical ganglion. We now have shown that GABA or glutamate is present in
      virtually all of the inputs to sympathetic preganglionic neurons projecting to
      the superior cervical ganglion and in essentially all of the inputs to
      sympathetic preganglionic neurons supplying the adrenal medulla. These findings
      are consistent with the hypothesis that all fast synaptic transmission in central
      autonomic pathways may be mediated by either excitatory or inhibitory amino
      acids. Furthermore, we showed a statistically significant difference in the
      proportion of glutamate-immunoreactive inputs between sympathetic preganglionic
      neurons projecting to the superior cervical ganglion and sympathoadrenal neurons
      (data from Llewellyn-Smith et al. [Llewellyn-Smith, I.J., Phend, K.D., Minson,
      J.B., Pilowsky, P.M., Chalmers, J.P., 1992. Glutamate immunoreactive synapses on
      retrogradely labelled sympathetic neurons in rat thoracic spinal cord. Brain Res.
      581, 67-80]), with preganglionics supplying the adrenal medulla receiving more
      excitatory inputs than those supplying the superior cervical ganglion. This
      increased excitatory input to sympathoadrenal neurons may explain the predominant
      activation of these neurons following baroreceptor unloading.

PMID- 9760047
TI  - Neurochemical markers in the nervous plexus of the canine glottis.
AB  - The structure of the nervous network and the distribution of tyrosine hydroxylase
      (TH)- and various neuropeptide-containing nerves were immunohistochemically
      studied in the glottis of the dog. The nervous network in the glottis revealed
      apparent regional differences in morphology. The nervous network in the
      cartilaginous vocal fold of the posterior glottis consisted of nerve bundles
      running parallel to the edge of the vocal fold. Only a small number of nerve
      bundles were observed in the anterior glottis, specifically in membranous vocal
      fold. In the subepithelial layer of the posterior glottis, a moderate number of
      galanin (GAL)-immunoreactive nerve fibers were observed, while only a few fibers
      were present in the anterior glottis. Numerous vasoactive intestinal peptide
      (VIP)-, GAL-, methionine-enkephalin (ENK)- and TH-immunoreactive nerve fibers
      were observed within and around the laryngeal submucosal seromucous gland. Many
      TH- and neuropeptide Y (NPY)-immunoreactive fibers were arranged around the blood
      vessels. In the epithelia, free nerve endings with immunoreactivity for substance
      P (SP) and calcitonin gene-related peptide (CGRP) was observed. Furthermore,
      nerve cell bodies with SP-, VIP-, GAL-, ENK-, and NPY-immunoreactivity were
      observed in the deep region of the submucosal layer. The results from the present
      study suggest that there is autonomic regulation of the glottis. Regional
      structural differences in the nervous network of the glottis may reflect
      functional differences.

PMID- 9760048
TI  - Calcium transients evoked by action potentials in the somata of chick ciliary
      neurons.
AB  - The effect of action potentials on the calcium concentration in the somata of
      chick ciliary neurons ([Ca2+]s) was determined by loading these with the calcium
      indicator calcium green-1. Following trains of 1-10 impulses (30 Hz) to the
      postganglionic nerve, the [Ca2+]s increased rapidly and then declined along a
      single exponential with a time constant of 0.70 +/- 0.04 s (fast phase). After
      trains of 20 or 50 impulses, the elevated [Ca2+]s declined as the sum of two
      exponentials, with time constants of 0.78 +/- 0.12 s (fast phase) and 4.0 +/- 0.4
      s (moderate phase). After a 600-impulse postganglionic train of impulses, the
      elevated [Ca2+]s declined quickly over about 1 s, and then as the sum of two
      exponentials: that of the moderate phase and a slower component with a time
      constant of 109 +/- 16 s (slow phase). Similar time courses were observed
      following stimuli to the preganglionic nerve. Caffeine (3 mM) and ryanodine (20
      microM) both sped the fast phase and slowed the moderate phase of [Ca2+]s
      decline. Carbonyl cyanide m-chlorophenyl hydrazone (CCCP, 2 microM) slowed the
      slow phase, without affecting the other phases of decline. These results are
      discussed in relation to identifying the mechanisms responsible for these
      different phases of Ca2+ removal.

PMID- 9760049
TI  - Effect of intravenous administration of melatonin on the efferent activity of the
      adrenal nerve.
AB  - The effect of intravenous administration of melatonin on the efferent activity of
      the adrenal nerve was investigated in the rat. Intravenous infusion of 1 or 2 ng
      melatonin resulted in a decrease, and 10 or 20 ng or larger amount of melatonin
      caused an increase in the efferent activity of the adrenal nerve. The least
      effective dose for the suppressive activity of melatonin was 100 pg and the
      response is dose-related. Administration of either 1 ng or 10 ng of melatonin did
      not change the plasma glucose concentration until 30 min after the
      administration. Hepatic vagotomy eliminates the inhibitory effect of melatonin.
      These results suggest that melatonin sensors in the hepato-portal region and
      melatonin receptors in the SCN play important roles in the regulation of
      sympathetic outflow to the adrenal medulla.

PMID- 9760050
TI  - A target specific pathway from nitric oxide synthase immunoreactive preganglionic
      sympathetic to superior cervical ganglion neurons innervating the submandibular
      salivary gland.
AB  - The correlations between nitric oxide synthase (NOS)-immunoreactive (NOS-ir)
      preganglionic sympathetic neurons (PSNs) in the thoracic spinal cord and the
      neurons in the superior cervical ganglia (SCG) were studied with special
      reference to target specificity. NOS-ir neurons were distributed in the
      intermediate gray of the spinal cord and most numerous in the intermediolateral
      subnucleus of the PSNs. NOS-ir PSNs received direct synaptic contacts from
      tyrosine hydroxylase-ir, 5-hydroxytryptamine-ir, gamma-amino butyric acid-ir, and
      phosphate-activated glutaminase-ir axons. A majority of PSNs projecting to SCG
      were NOS-ir but some were NOS-negative. Large SCG neurons surrounded by a dense
      network of NOS-ir axons from PSNs projected to the submandibular salivary gland.
      NPY-ir small SCG neurons devoid of NOS-ir PSN innervation projected to blood
      vessels. SIF cells in the SCG were NOS-negative and provided with a meshwork of
      NOS-ir axons. The present results suggest a subpopulation of SCG neurons may be
      concerned with a distinct functional category in the rat under the influence of
      NOS-ir preganglionic sympathetic neurons.

PMID- 9760051
TI  - Extrinsic denervation increases myenteric nitric oxide synthase-containing
      neurons and inhibitory neuromuscular transmission in guinea pig.
AB  - Enteric nerves can function normally without connections with the central nervous
      system. A contributing component of the functional autonomy exhibited by enteric
      nerves is their plasticity. In the present study, the number of nitric oxide
      synthase-immunoreactive (NOS-ir) myenteric neurons and inhibitory neuromuscular
      transmission were studied in extrinsically denervated ileal segments. Segments of
      ileum were extrinsically denervated by crushing the mesenteric blood vessels
      supplying a loop of ileum in anesthetized guinea pigs. Some unoperated animals
      were treated with capsaicin or 6-hydroxydopamine (6-OHDA) to disrupt primary
      afferent and sympathetic nerves, respectively. NOS-ir was localized using
      indirect immunofluorescence. Nerve-mediated relaxations of longitudinal muscle
      were studied in vitro using standard methods. At 7 weeks after extrinsic
      denervation there was a 93% increase in the number of NOS-ir myenteric neurons.
      The number of neurons containing detectable vasoactive intestinal peptide-ir
      neurons was not changed after extrinsic denervation. Neurogenic relaxations
      caused by 10, 20 and 50 Hz transmural stimulation were larger in extrinsically
      denervated tissues compared to control tissues. The NOS antagonist, nitro-L
      arginine (300 microM) inhibited neurogenic relaxations in control and
      extrinsically-denervated tissues. Capsaicin- but not 6-OHDA-treatment mimicked
      the effects of extrinsic denervation on NOS-ir and neurogenic relaxations of the
      longitudinal muscle. Active or passive properties of the longitudinal muscle were
      unaffected by extrinsic denervation. These data indicate that extrinsic
      denervation is associated with an increase in the number of myenteric neurons
      expressing detectable NOS-ir and potentiation of inhibitory transmission to
      longitudinal muscle. This effect is due to loss of extrinsic sensory nerves.

PMID- 9760052
TI  - Effect of generalised sympathetic activation by cold pressor test on cerebral
      haemodynamics in healthy humans.
AB  - There is no general agreement regarding several aspects of the role of the
      sympathetic system on cerebral haemodynamics such as extent of effectiveness,
      operational range and site of action. This study was planned to identify the
      effect of a generalised sympathetic activation on the cerebral haemodynamics in
      healthy humans before it is masked by secondary corrections, metabolic or
      myogenic in nature. A total of 35 healthy volunteers aged 20-35 underwent a 5 min
      lasting cold pressor test (CPT) performed on their left hand. The cerebral blood
      flow (CBF) velocity in the middle cerebral arteries and arterial blood pressure
      were recorded with transcranial Doppler sonography and with a non-invasive finger
      cuff method, respectively. The ratio of arterial blood pressure to mean blood
      velocity (ABP/Vm) and Pulsatility Index (PI) were calculated throughout each
      trial. CPT induced an increase in mean ABP (range 2-54 mmHg depending on the
      subject) and only a slight, though significant, increase in blood velocity in the
      middle cerebral artery (+2.4 and +4.4% on ipsi- and contralateral side,
      respectively). During CPT, the ratio ABP/Vm increased and PI decreased in all
      subjects on both sides. These changes began simultaneously with the increase in
      blood pressure. The increase in ABP/Vm ratio is attributed to an increase in the
      cerebrovascular resistance, while the concomitant reduction in PI is interpreted
      as due to the reduction in the compliance of the middle cerebral artery. The
      results suggest that generalised increases in the sympathetic discharge, causing
      increases in ABP, can prevent concomitant increases in CBF by acting on both
      small resistance and large compliant vessels. This effect is also present when a
      slight increase in blood pressure occurs, which suggests a moderate increase in
      the sympathetic discharge, i.e. when ABP remains far below the upper limit of CBF
      autoregulation.

PMID- 9760054
TI  - Organ and development related difference in tissue norepinephrine concentrations
      in Dahl rats.
AB  - To determine organ and development related differences in tissue norepinephrine
      concentration (tNE) in Dahl salt-sensitive (S) and -resistant (R) rats, we
      measured the tNE of 16 organs, including the heart (left ventricle), kidney,
      cerebrum, brain stem, stomach, jejunum, ileum, colon, spleen, pancreas, liver,
      aorta, lung, bone, salivary gland, and muscle, at 1, 3, 5, 7, 9, 11 weeks old.
      Large differences were found in tNE among the organs of both S and R rats,
      ranging from 4.0 +/- 1.1 ng/g tissue (the bone of S rats) to 1234.8 +/- 32.5 ng/g
      tissue (the salivary gland of R rats). tNE in R rats increased development
      dependently in 12 of 16 organs, but did not significantly change in the other
      three organs, and decreased in the bone. On the other hand, the development
      dependent increase in tNE was suppressed in S rats, and the tNE values of S rats
      were significantly lower than those of R rats in 14 of 16 organs. To eliminate
      the baroreflexive effects on tNE, another group of 5-week-old S and R rats were
      subjected to sinoaortic denervation (SAD) or the sham operation. The tNE was
      measured in 10 organs in these animals at 9 weeks old. SAD did not alter the tNE
      in most of the organs in both S and R rats. There was no significant differences
      in mean arterial pressure (MAP) between S and R rats with baroreceptor intact at
      9 weeks old. SAD slightly but significantly increased MAP in S rats, whereas not
      in R rats. There was no significant differences in plasma NE concentration (pNE)
      between S and R rats with the baroreceptor intact. SAD did not alter pNE in S or
      R rats. These results demonstrate that variations of the tNE were dependent on
      the organ and development. Many organs of S rats had lower tNE than those of R
      rats. The developmental-dependent increases in tNE in S rats were suppressed,
      compared with those in R rats. These tNE behaviors in S rats may not be related
      to blood pressure or baroreflex sensitivity, but might be involved in an abnormal
      sympathetic nerve activity.

PMID- 9760055
TI  - Magnitude of skin vasomotor reflex represents the intensity of nociception under
      general anesthesia.
AB  - Because nociceptive stimuli induce the skin vasomotor reflex (SVmR), the
      assessment of the SVmR would be a useful indicator to represent nociception. We
      examined 39 adult patients for the relationship between the magnitude of the SVmR
      and the intensity of nociceptive stimulus that induced the SVmR. Under oxygen
      nitrous oxide (50%) and sevoflurane anesthesia, the SVmR was induced by an
      electrical impulse to the ulnar nerve and detected by a laser Doppler flowmeter.
      Study 1: under the end-tidal concentrations of sevoflurane at 1.2% (n = 10), 1.7%
      (n = 9) or 2.2% (n = 10), the SVmR was tested by a 2-s, 50-Hz tetanic electrical
      impulse with a current intensity changing (40, 50 or 60 mA) in a randomized
      order. Study 2: under the end-tidal concentration of sevoflurane at 1.7% (n =
      10), the SVmR testing was performed with a 50-mA, 50-Hz tetanic electrical
      impulse with the current duration changing (2, 3 or 4 s) in a randomized order.
      The studies demonstrated significant correlations of (1) the current intensity
      which induces the skin vasomotor reflex (SVmR) vs. the magnitude of the SVmR
      under the three different anesthesia depths, (2) the anesthesia depth vs. the
      magnitude of the SVmR (inverse proportion) under the same current intensity and
      (3) the duration of electrostimulation vs. the magnitude of the SVmR. Thus, the
      SVmR could be helpful for the objective assessment of nociception and anti
      nociceptive effects in individual cases.

PMID- 9760053
TI  - I1-imidazoline receptors and cholinergic outflow to the airways.
AB  - We examined the role of I1-imidazoline receptors in the control of airway
      function, by testing the effects of systemic administration of the I1-imidazoline
      agonist moxonidine on reflex responses of tracheal smooth muscle (TSM) tone to
      either lung deflation or mechanical stimulation of intrapulmonary rapidly
      adapting receptors. Experiments were performed in either alpha-chloralose
      anaesthetized or decorticate, paralyzed and mechanically ventilated beagle dogs.
      Moxonidine (10-100 microg/kg) administered via three different routes (the
      femoral vein, muscular branch of superior thyroid artery, and vertebral artery)
      attenuated TSM responses to stimulation of airway sensory nerve fibers by two
      different ways, and caused a decrease in arterial pressure and heart rate. These
      effects were dose-dependent, and were significantly reversed by efaroxan (an I1
      imidazoline and alpha2-adrenergic blocker) administered via the vertebral artery.
      Intravertebral efaroxan abolished the hemodynamic effects of moxonidine.
      Intravenous moxonidine (10-100 microg/kg) did not alter airway smooth muscle
      responses to electrical stimulation of the peripheral vagus nerve. In addition,
      in vitro moxonidine (1-100 microg/ml) had no effect on contractile responses to
      increasing doses of acetylcholine. These findings indicate that moxonidine may
      act at a central site to suppress reflex airway constriction, even when given
      into the systemic circulation. Given the presence of I1-imidazoline sites and
      alpha2-adrenergic receptors in brain regions participating in airway reflexes,
      these receptor classes may be involved in brainstem control of the cholinergic
      outflow to the airways.

PMID- 9760056
TI  - Expression and physiological actions of neuropeptide Y in guinea pig
      parasympathetic cardiac ganglia.
AB  - Guinea pig atrial whole mount preparations containing the parasympathetic cardiac
      ganglia were used to establish the expression, distribution and actions of
      neuropeptide Y (NPY) in atrial tissues. NPY-immunoreactive fibers densely
      innervated the atrial myocardium and blood vessels. Fibers containing NPY also
      innervated intrinsic parasympathetic cardiac neurons. Four percent of the cardiac
      neurons, identified using microtubule associated protein-2 antiserum, were NPY
      positive. An endogenous source of NPY was confirmed with reverse transcription
      PCR which demonstrated the presence of proNPY mRNA. Sixty percent of the
      parasympathetic cardiac neurons were hyperpolarized by local application of NPY.
      NPY also decreased the amplitude and duration of the action potential after
      hyperpolarization in 60% of the neurons and decreased the fast excitatory
      postsynaptic potential in about 50% of the cells. These observations indicate
      that NPY is anatomically positioned to directly alter the output of the
      parasympathetic cardiac ganglia either by hyperpolarizing the cardiac neurons or
      by decreasing the fast synaptic input which drives individual neurons.

PMID- 9760057
TI  - Further characterization of stimulus interaction of cat carotid chemoreceptors.
AB  - The hypothesis that the maximal response to pCO2 of carotid body chemoreceptors
      would be the same regardless of pO2, if the receptor molecule behaves like a
      hemoglobin molecule, was investigated using single or a few fiber carotid body
      chemoreceptors in cats in vivo which were anesthetized and artificially
      ventilated. In one series, graded levels of CO2 inhalation in steady-state at
      p(a)O2 = 354 +/- 19 Torr showed a linear response from 1 to 20.1 +/- 2.3 imp/s
      for p(a)CO2 increase from 32 to 178 +/- 18 Torr, and at p(a)O2 of 48 +/- 3.8
      Torr, from 3.8 to 18.6 +/- 1.7 imp/s for p(a)CO2 increase from 21 to 109 +/- 11
      Torr, levelling off thereafter. In another series of multi-fiber preparation,
      close intra-arterial injection of blood plus saline containing pCO2 of about 270
      Torr gave peak responses of 44 +/- 9, 42 +/- 6 and 42 +/- 7 imp/s at p(a)O2 of 40
      +/- 4, 82 +/- 6 and 388 +/- 18 Torr, respectively. Thus, the chemosensory
      responses to p(a)CO2 reached the same level of maximal activity regardless of
      p(a)O2. Taken together, the maximal responses in both steady-state and transient
      state to p(a)CO2 appeared to be the same at hypoxic and hyperoxic p(a)O2. This
      stimulus-response relationship of the receptor molecule is analogous to O2-CO2
      interaction with hemoglobin molecule with a Bohr effect, reaching a saturation
      point at a finite pO2.

PMID- 9760058
TI  - Pig, donkey and buffalo meat as a source of some coccidian parasites infecting
      dogs.
AB  - Experimental infection of dogs with meat samples (oesophagus, heart and
      diaphragm) from each of 105 pigs, 11 donkeys and 17 Egyptian water buffaloes
      indicated that they contained the infective stages of some coccidian parasites of
      dogs. The dogs which were fed pig meat shed in their faeces Isospora ohioensis,
      I. canis oocysts and Sarcocystis miescheriana sporocysts after prepatent periods
      of 3-5, 4-7 and 9-10 days, respectively. The dogs which were fed donkey meat
      excreted only I. ohioensis oocysts and Sarcocystis bertrami sporocysts after
      prepatent periods of 3 and 11 days, respectively. However, the dogs which were
      fed buffalo meat shed in their faeces I. ohioensis, I. canis and Hammondia
      heydorni oocysts with prepatent periods of 1, 1 and 7 days, respectively.

PMID- 9760059
TI  - Selection and development of a Spanish precocious strain of Eimeria necatrix.
AB  - A precocious line of Eimeria necatrix (PEN E-281/20) with an abbreviated life
      cycle was derived from a Spanish field strain (E-281) by repeated passages of the
      first shed oocysts recovered from the caecal contents of previously infected
      chickens. After 20 passages, the 'useful' prepatent period (time from infection
      to obtaining sufficient oocysts to repassage) of the parasite was reduced by 30 h
      (from 148 to 118 h). The earliest oocysts found in the caecal content were 114 h
      postinfection (hpi), on the 19th passage. The pathogenicity of the parasite was
      reduced in comparison with the parent strain, its immunogenicity against
      homologous and heterologous strains was maintained and its reproductive capacity
      was similar to or higher than that of the parent strain. Compared with the parent
      strain, the second generation of schizonts was reduced in size (reduced
      pathogenicity), third generation schizonts were bigger and with more merozoites
      (maintenance of the reproductive index) and the life cycle progressed faster from
      the second generation of schizonts (reduction of prepatent period). Complete
      second schizogony, from trophozoites to mature schizonts was observed frequently
      in the caeca of birds infected with both parent and precocious lines.

PMID- 9760060
TI  - Diagnosis of porcine cysticercosis: a comparative study of serological tests for
      detection of circulating antibody and viable parasites.
AB  - Epidemiological studies of porcine cysticercosis require identification of pigs
      harbouring viable Taenia solium cysticerci and estimates of the degree of
      exposure to the parasite in the pig population destined for human consumption.
      Identification of infected pigs with viable larvae is achieved through detection
      of their secretory products. However, detectable levels of circulating antibody
      may also be present in the absence of viable larvae. In this study, both types of
      tests have been evaluated in groups of pigs experimentally infected with T.
      solium. Detection of viable cysticerci was achieved using a monoclonal antibody
      based (HP10) antigen capture assay. HP10 epitope-bearing antigens have now been
      demonstrated in T. solium and T. crassiceps cyst fluid and excretion/secretions.
      Serum antibodies were measured in ELISA assays using two parasite preparations as
      antigens; T. solium cyst fluid and T. crassiceps cyst fluid antigens bearing the
      HP10 epitope. Low-background values were obtained with sera from non-infected
      animals in all the assays used. In heavily infected pigs, both antigens and
      antibodies were detected at least 29 days and up to 200 days post-infection (pi),
      while in lightly infected pigs antigen and antibodies were first observed between
      61-97 days pi. Thus, the levels of the serum antigen and antibody varied with the
      intensity of the infection.

PMID- 9760061
TI  - Helminth and protozoan gastrointestinal tract parasites in captive and wild
      trapped African non-human primates.
AB  - The objective of this study was to investigate the gastro-intestinal (GIT)
      parasites commonly occurring in captive and wild-trapped (WT) non-human primates
      (baboons, vervets and Sykes) in Kenya and compare their prevalence. Three hundred
      and fifteen faecal samples were subjected to a battery of diagnostic tests,
      namely, direct smear, modified formal ether sedimentation, Kato thick smear,
      Harada-Mori techniques for parasite detection and culture to facilitate nematode
      larvae identification. Of these, 203 (64.4%) harboured helminths and 54 (17.1%)
      had protozoa. The helminth parasites comprised Strongyloides fulleborni 141
      (44.8%), Trichuris trichuira 200 (63.5,%), Oesophagostomum sp. 48 (15.2%),
      Trichostrongylus sp. 73 (23.2%), Enterobius vermicularis 44 (14.0%), Schistosoma
      mansoni 4/92 (4.3%) and Streptopharagus sp. 68 (21.6%). Protozoan parasites
      consisted of Entamoeba coli 204 (64.8%), Balantidium coli 127 (40.3%) and
      Entamoeba histolytica 78 (24.8%). Both WT and colony-borne (CB) primates had
      similar species of parasites, but higher prevalences of protozoan infection were
      observed in CB baboons while helminth infections were relatively more common in
      WT primates. Some of the parasites observed in this study are reported to be
      zoonotic in various parasitological literatures. Chemoprophylaxis and other
      managerial practices were believed to be responsible for the lower worm
      prevalence in CB primates. Similar intervention against protozoa and other agents
      will not only improve primate health, but also increase safety to animal handlers
      and colony workers.

PMID- 9760062
TI  - Natural prevalence of infection with Ehrlichia (Cytoecetes) phagocytophila of
      Ixodes ricinus ticks in Scotland.
AB  - Ixodes ricinus nymphs and adults were collected from vegetation and from sheep at
      four sites in Scotland typical of areas endemic for tick-borne fever in sheep
      caused by infection with Ehrlichia (Cytoecetes) phagocytophila (Rickettsiales).
      The great majority of ticks examined was from woodland sites adjacent to sheep
      farms where there was a high probability of them feeding on roe deer (Capreolus
      capreolus) in a non-domestic focus of infestation and infection. Ticks were
      examined for infection by five methods. Batches of ticks were examined either by
      feeding on susceptible sheep or by feeding on rabbits and then prepared as
      stabilate which was inoculated into susceptible sheep. The sheep were monitored
      for clinical signs of tick borne fever. Batches of ticks were examined by
      polymerase chain reaction for Ehrlichia phagocytophila. Salivary glands were
      dissected out and stained by the Feulgen method to detect Ehrlichia masses, and
      were examined by indirect fluorescent antibody test. Each of the methods detected
      infection in ticks and the prevalence of infection in nymphs with the various
      methods ranged from >0.25% to 2.0%. Small samples of adults examined by Feulgen
      staining of salivary glands indicated infection prevalences of 2.1% in males and
      1.6% in females. It is considered that these low infection prevalences may be
      typical of natural foci of infection where deer could be a major host of ticks
      and E. phagocytophila.

PMID- 9760063
TI  - Efficacy of ivermectin in a controlled release formulation against Psoroptes ovis
      (Hering, 1838) gervais, 1841 (Acari: Psoroptidae) on sheep.
AB  - Three trials including 42 sheep were conducted in Brazil or Germany to evaluate
      the therapeutic (two trials) and prophylactic (one trial) efficacy of an
      ivermectin controlled release capsule (CRC) against Psoroptes ovis infestation.
      In one therapeutic trial naturally infested sheep were used while in the other
      trials infestations were experimentally induced. In each trial half of the
      animals were treated on Day 0 with one ivermectin controlled release capsule that
      delivers ivermectin at a rate of 1.6 mg/day for approximately 100 days, that is
      20 mcg/kg/day to a 80 kg animal, while the other half remained untreated. In both
      therapeutic trials mites were counted in skin scrapings and their presence was
      recorded at predilection sites one day before treatment and at weekly intervals
      from Day 7 to Day 56. In the trial conducted to evaluate the prophylactic
      efficacy the sheep were experimentally infested with P. ovis 21 and 28 days post
      treatment and mites were counted and recorded at predilection sites on Days 42,
      49 and 56. The ivermectin controlled release capsule was completely effective in
      eliminating the P. ovis mites within 28 days of administration and it prevented
      the establishment of an infestation of P. ovis induced 21 and 28 days after
      administration.

PMID- 9760064
TI  - Sex differences in the disposition of albendazole metabolites in sheep.
AB  - Sex differences in the disposition of albendazole metabolites in sheep after oral
      administration of 20 mg/kg of netobimin have been studied. Some kinetic
      parameters of both metabolites show statistical differences between sexes; the
      sulphoxide and sulphone t1/2beta and MRT were lower in male animals than in
      females. Peak concentrations and AUC of sulphone metabolites were higher in males
      suggesting a greater oxidation rate compared with females. Urine excretion of
      albendazole metabolites, sulphoxide, sulphone, and amino sulphone appeared to be
      greater in female sheep than in males, mainly the sulphoxide metabolite. These
      differences between sexes can be caused by male sexual hormones, because
      testosterone and progesterone can induce or inhibit the microsomal Cytochrome
      P450 metabolism. Plasma protein-binding of albendazole sulphoxide and albendazole
      sulphone has been studied between male and female sheep, also their binding to
      sheep albumin and globulins. Both albendazole metabolites readily bind to sheep
      albumin and globulins. Male animals show a significantly lower binding of
      albendazole metabolites than females. These differences could be responsible for
      the non-esterified fatty acids (NEFA) present in the plasma. Males have
      significantly higher plasma levels of NEFA than females and which may compete
      with albumin for binding to albendazole metabolites.

PMID- 9760065
TI  - Seroprevalence of Taenia solium cysticercosis in pigs in a rural community of
      Honduras.
AB  - Several retrospective studies have shown that human Taenia solium cysticercosis
      is endemic in Honduras, but very few reports of porcine cysticercosis in rural
      communities have been published. To determine the local prevalence of this
      disease in pigs, a serological survey has been undertaken in a rural community,
      Salama, in the Department of Olancho in central Honduras. Eighty-five families
      raising pigs in the community were randomly selected and sera were obtained from
      pigs older than one month of age. The sera were examined by the enzyme-linked
      immunoelectrotransfer blot assay (EITB). Of 192 porcine sera, 27.1% (52) were
      positive by the EITB. Seropositivity did not correlate with age and sex by
      statistical analysis. With respect to the number and the frequency of recognition
      of the seven diagnostic glycoprotein bands in the EITB, 67.3% of the positive
      serum specimens recognized only one band and 80.8% of them recognized GP42-39.
      Since recognition of GP42-39 has been reported as a characteristic of late
      infection, these results suggest that most of the seropositive pigs were in the
      late stage of infection (more than 5-8 weeks postinfection). It seems that pigs
      in this community may be infected with this parasite soon after the birth and be
      in a hyperendemic steady state. In view of a high prevalence of antibodies to T.
      solium in pigs or characteristics of the antigen detected by the EITB, the
      infection pressure of T. solium appears to be very high in this community. This
      is probably the case in most of the communities in Honduras.

PMID- 9760069
TI  - Solitary intracranial plasmacytoma: case report and review of management.
AB  - A rare occurrence of solitary intracranial plasmacytoma arising from the meninges
      over the left hemisphere is reported. Clinical features and management of the
      case are described with review of literature.

PMID- 9760066
TI  - Growth inhibition of newly established human glioma cell lines by leukemia
      inhibitory factor.
AB  - We have established three new cell lines deriving from malignant human gliomas.
      The cell lines were described in terms of both morphology and growth
      characteristics. Most cells in all three cell lines expressed the neuroepithelial
      marker protein GFAP. In terms of growth characteristics, the cells showed only
      slight differences. The cell lines showed no expression of the neural form of the
      c-src gene, pp60c-srcN, but did express the ubiquitous form, pp60c-src. The
      established glioma cell lines were also examined for expression of members of the
      neuropoietic cytokine family, CNTF and LIF, and their respective receptor
      components CNTFRalpha, LIFRbeta and gp130. With the exception of CNTFRalpha both
      the ligands and their receptor components were expressed in similar amounts in
      all three cell lines. The presence of ligand and receptor prompted us to study
      the effects of exogenously supplied factors on the growth of the glioma cell
      lines. Whereas LIF induced a high c-fos expression, only low c-fos induction was
      observed upon CNTF treatment. Accordingly, CNTF did not have any noticeable
      effects on glioma cell growth in culture, while LIF mediated an inhibiting effect
      on the growth of the three glioma cell lines in culture.

PMID- 9760070
TI  - Clusters of histologic characteristics in children with infratentorial neuroglial
      tumors. The Childhood Brain Tumor Consortium.
AB  - Five quantitative histologic factors, differing linear combinations of 26
      reliably recognized histologic features, account for much of the histologic
      variance in 1068 children with infratentorial neuroglial tumors in the Childhood
      Brain Tumor Consortium (CBTC) database. In this study, we used the scores on the
      Spongy, Proliferative, Ring, Fibrillary, and Nuclear factors in cluster analyses
      and identified 11 clusters of children's tumors. Each had statistically
      significant differences in histology and relative histologic homogeneity. Three
      clusters had ependymoma-like histologic features; 4 had astrocytoma-like
      features; and 4 had primitive neuroectodermal-like (PNET or medulloblastoma)
      features. Each cluster had a unique high/low mean factor score pattern. Multiple
      operative and other clinical features characterized the three groups of clusters.
      We used Kaplan-Meier survival models to test for differences in survival among
      clusters and proportional hazards survival models to adjust for associated
      covariates. Among the 'ependymoma' clusters the 5 year survival probability
      ranged from 0.25 to 0.54. Among the 4 'astrocytoma' clusters, 5 year survival
      probability ranged from 0.59 to 0.94. The 5 year survival probability for the
      'medulloblastoma' clusters ranged from 0.20 to 0.44. Within the three groups,
      clusters had differing covariates associated with survival. The tumor clusters
      identified in this study ensure relatively homogeneous histologic subsets. The
      five factor scores of a child's tumor provide the basis for finding the cluster
      nearest to that tumor. We propose that this tumor clustering strategy be employed
      for selection of children and for analyses of therapeutic clinical trials.

PMID- 9760067
TI  - Chemosensitivity of human malignant glioma: modulation by p53 gene transfer.
AB  - Loss of wild-type p53 activity is one of the most common molecular abnormalities
      in human cancers including malignant gliomas. The p53 status is also thought to
      modulate sensitivity to irradiation and chemotherapy. Here, we studied the effect
      of a p53 gene transfer on the chemosensitivity of three human glioma cell lines
      with different endogenous p53 status (LN-229, wild-type; LN-18, mutant; LN-308,
      deleted), using the murine temperature-sensitive p53 val135 mutant. Expression of
      mutant p53 enhanced proliferation of LN-308 cells but reduced proliferation in
      the other cell lines. Expression of wild-type p53 caused reversible growth arrest
      of all cell lines but failed to induce apoptosis. Growth arrest induced by wild
      type p53 was associated with strong induction of p21 expression. Strong induction
      of BAX expression and loss of BCL-2 expression, which are associated with p53
      dependent apoptosis rather than growth arrest, were not observed. Wild-type p53
      failed to sensitize glioma cells to cytotoxic drugs including BCNU, cytarabine,
      doxorubicin, teniposide and vincristine. The combined effects of wild-type p53
      gene transfer and drug treatment were less than additive rather than synergistic,
      suggesting that the intracellular cascades activated by p53 and chemotherapy are
      redundant. Unexpectedly, forced expression of mutant p53 modulated drug
      sensitivity in that it enhanced the toxicity of some drugs but attenuated the
      effects of others. These effects may represent a dominant negative effect of
      mutant p53 in LN-229 cells which have wild-type p53 activity but must be
      considered a gain of function-type effect in the other two cell lines which have
      no wild-type p53 activity. Importantly, no clear-cut pattern emerged among the
      three cell lines studied. We conclude that somatic gene therapy based on the
      reintroduction of p53 will limit the proliferation of human malignant glioma
      cells but is unlikely to induce clinically relevant sensitization to chemotherapy
      in these tumors.

PMID- 9760068
TI  - A dominant-negative mutant of the platelet-derived growth factor A-chain
      increases survival of hamsters implanted intracerebrally with the highly invasive
      CxT24-neo3 glioblastoma cell.
AB  - Evidence is accumulating to suggest a role for PDGF in stimulating malignant
      growth in astrocytoma, although it has been obtained using model systems (growth
      in 2-dimensional cell culture, athymic nude mice) that do not assess the complex
      interactions of these tumors with normal brain tissue. In the current study, the
      highly invasive hamster glioblastoma cell line CxT24-neo3 was used as a model to
      study the role of platelet-derived growth factor (PDGF) in mediating malignant
      growth both in vitro and in vivo when implanted directly into the right lateral
      ventricle of the brain. Co-expression of PDGF B-chain mRNA and PDGF alpha
      receptors was detected in these cells, indicating potential for autocrine
      activation of their growth. CxT24-neo3 cells transfected with wild-type and
      receptor binding-deficient forms of the PDGF A- and B-chains displayed
      alterations in their abilities to grow as three-dimensional spheroids, with
      overexpression of wild-type B-chain resulting in increased spheroid formation,
      but a decreased rate of spheroid growth. Influence of these PDGF polypeptides on
      tumor invasion and survival time in vivo was evaluated following implantation of
      these spheroids in the brain. While all hamsters implanted with control spheroids
      died within 21 d (average 17 d), those implanted with cells expressing the
      receptor binding-deficient A-chain survived for much greater periods of time
      (average 80 d). Modest increases in survival were also seen in cells stably
      expressing wild-type A-chain (25 d) and mutant B-chain (26 d) proteins. The
      present study suggests an important role of PDGF in mediating the malignant
      growth of the CxT24-neo3 cell line in cerebral cortex, possibly via paracrine
      interactions with normal cortical cell types (i.e., glia, neurons).

PMID- 9760071
TI  - Atypical and malignant meningiomas: an outcome report of seventeen cases.
AB  - Limited data are available concerning the outcome of patients with atypical and
      malignant meningiomas. We therefore analyzed the outcome of seventeen patients
      with meningiomas (9 atypical; 8 malignant) at Thomas Jefferson University
      Hospital between 1973 and 1996. Strict adherence to the 1993 WHO criteria for the
      typing of CNS tumors was maintained. The median potential follow-up period for
      all patients was 87 months. The age at diagnosis ranged from 22 to 72 (mean 51.8
      years). There were 5 males and 12 females. The mean tumor diameter was 4.45 cm.
      Of the 16 cases where the extent of surgical resection was known, 4 were partial
      and 12 were complete resections. Six patients (35%) had dural or cortical
      invasion by tumor. Fifteen patients received postoperative megavoltage photon
      irradiation (mean 61 Gy). One of these fifteen pts. received an additional 20 Gy
      with Au-198 implantation and 1 received post-radiation chemotherapy for recurrent
      disease. The overall survival rate for all patients at 5 and 10 years were 87%
      and 58% respectively. The 5- and 10-year survival rates for atypical meningiomas
      were 87% and 58%; for malignant meningiomas the survival rates were 60% and 60%
      respectively. Five patients (30%) have died. Three of these 5 patients initially
      received less than 54 Gy to the tumor bed and have died of recurrent disease.
      Local disease progression was documented in 11 patients (65%) after surgery and
      in 3 patients (18%) after radiation. There was an improvement in performance
      status in 3 (18%) patients with a decline and no change seen in 1 (6%) and 13
      (77%) respectively after receiving radiation. There appeared to be no difference
      in survival in patients as a function of dural or cortical invasion. Long term
      survival is possible for patients with atypical and malignant meningiomas treated
      with surgery and post-operative radiation. We are unable to distinguish a
      difference in outcome between these two pathological entities. Dural and cortical
      invasion were not associated with a decrease in survival. In addition, improved
      tumor control and survival may be associated with increased radiation dose.

PMID- 9760072
TI  - Synchronous radiochemotherapy in unfavorable brain tumors of children and young
      adults.
AB  - The prognosis of patients with incompletely resected malignant brain tumors is
      almost fatal. In an attempt to improve the outcome of children and young adults
      with unfavorable brain tumors an intensive multimodal therapeutic strategy was
      developed combining simultaneous (hyper)fractionated external beam irradiation
      and conventional adjuvant chemotherapy after initial surgery. 17 patients aged
      between 2.10 and 25.11 years were entered into the study. 16/17 patients were
      treated according to the German/Austrian Pediatric Brain Tumor Study Group
      multicenter trial HIT '91. They are not protocol patients of this HIT '91 trial.
      Induction chemotherapy consisted of 2 courses of ifosfamide (3 g/m2/d) on days 1
      3, etoposide (150 mg/m2/d) on days 4-6, methotrexate (5 g/m2) on days 15 and 22,
      cisplatin (40 mg/m2/d) and cytarabine (400 mg/m2/d) on days 29-31. Three weeks
      after the last dose of cisplatin/cytarabine the second course of chemotherapy was
      started. The last patient entered into the study received a modified therapy
      containing ifosfamide, cisplatin and etoposide. Synchronously at a median of 12
      days after initiation of chemotherapy 12/17 patients received local radiotherapy
      (6000-7040 cGy) to the brain and 5/17 patients craniospinal irradiation (3520 cGy
      with a tumor boost of 1400-2000 cGy). 4-6 weeks after completion of the second
      course of chemotherapy maintenance therapy was started with carmustine (CCNU) (75
      mg/m2) and carboplatin (400 mg/m2) each on day 1 and vincristine (1.5 mg/m2) on
      day 1, 8, 15. This course was repeated eight times every six weeks. 9/17 patients
      are alive at a median follow-up of 25 months (range 5-50) with 4 complete
      remissions, 2 partial remissions and 1 stable disease lasting 42+ months. Two
      patients, who initially had stable disease, progressed, but are still alive at
      31+ and 41+ months after diagnosis. Median progression-free survival and median
      overall survival is 19 and 36 months, respectively. Hematologic and methotrexate
      induced toxicity were severe and resulted in one therapy-related death. However,
      radiotherapy concomitant to chemotherapy appears to be an effective method of
      treatment for brain tumors with poor prognosis, though toxicity is severe in some
      cases.

PMID- 9760075
TI  - Identification of CNS neurons innervating the rat prostate: a transneuronal
      tracing study using pseudorabies virus.
AB  - The spinal and brain neurons that innervate the rat prostate were identified
      using the transneuronal tracing technique. Three groups of rats were prepared:
      (1) nerve intact, (2) bilateral pelvic nerve cut and right hypogastric nerve cut
      and (3) bilateral hypogastric nerve cut and right pelvic nerve cut. Pseudorabies
      virus (PRV) was injected into the ventral prostate on the left side. After 2-4
      days, the rats were perfused transcardially under deep anesthesia and the spinal
      cord and brain removed. PRV-labelled cells were identified using
      immunohistochemistry. After 3 days survival, sympathetic and parasympathetic
      preganglionic neurons were labelled with PRV. In addition, spinal interneurons
      were found in the dorsal gray commissure (DGC) of T13-S1. Rats with only one
      hypogastric nerve intact resulted in spinal labelling of sympathetic
      preganglionic neurons in the DGC and ipsilateral intermediolateral cell column
      (IML). In addition, many spinal interneurons were found from L1 to L6 in the
      medial gray. Rats with only one pelvic nerve intact displayed PRV-labelled cells
      in the parasympathetic preganglionic nucleus ipsilateral to the injection site.
      Spinal interneurons were present in the region of the IML and in the medial cord.
      In the brain, areas predominately labelled with PRV included the nucleus
      gigantocellularis and paragigantocellularis, raphe magnus, raphe pallidus, A5,
      Barrington's nucleus, central gray, ventral tegmental area, the paraventricular
      nucleus of the hypothalamus, lateral hypothalamus and medial preoptic area. These
      data demonstrate the sympathetic and parasympathetic spinal circuits and
      demonstrate the overlap of supraspinal innervation of the spinal interneurons.

PMID- 9760073
TI  - Significant change in tests of neurological impairment in patients with brain
      tumours.
AB  - There is a need for valid objective tests of neurological improvement or
      deterioration to more accurately define response or progression in phase II
      studies of malignant glioma. The Edinburgh Functional Impairment Tests (EFIT)
      incorporate objective measures of upper and lower limb function, memory and a
      rating scale for dysphasia. We examined the intra-observer repeatability of the
      (EFIT) 24 hours apart in 55 patients with brain tumors and stable neurological
      disease and the inter-rater repeatability in 33 patients in the perioperative
      period (54 dual assessments). Intra-observer studies of the four subtests, failed
      to demonstrate any learning effect and showed close agreement. Inter-rater
      studies were affected by a treatment effect (steroids) and identified slight
      inter-rater bias for the ten meter walk. Altman-Bland plots showed that the level
      of agreement was less good in patients with more severe impairment. Correction
      for the severity of handicap was possible using a simple formulae: (timed tests:
      [rater 1 - rater 2]/[rater 1 + rater 2], Williams Delayed Recall Test [WDRT]
      (rater 1 - 2/81). Using this correction, all intra- and inter-rater variance of
      patients tested within 12 hours were < 0.2. A change of > or = 0.2 for the timed
      tests and WDRT, and a change in dysphasia score of > or = 2, represent a
      significant change in impairment using the EFIT. The EFIT should be a useful
      addition in phase II studies where objectively recording response or time to
      progression is important.

PMID- 9760074
TI  - Transitional cell carcinoma presenting as a solitary brain lesion: a case report
      and review of the world literature.
AB  - Transitional cell carcinoma of the urinary tract will account for roughly 50,000
      new cases of cancer in the US this year. Metastatic involvement to the brain is
      uncommon with this malignancy. When it does occur, it is usually in the setting
      of widespread metastatic disease. A rare case of transitional cell carcinoma of
      the bladder presenting as a solitary brain lesion is reported. In addition, we
      reviewed the world literature regarding transitional cell carcinoma metastatic to
      the central nervous system. Our review suggests that metastatic transitional cell
      carcinoma of the central nervous system has become increasingly common as more
      effective chemotherapeutic regimens have been developed to control the primary
      disease. The recent literature also suggests that, much like other metastatic
      disease to the brain, outcome and survival in patients without widespread disease
      is improved by aggressive surgical and oncological management.

PMID- 9760076
TI  - AT1 receptors mediate chronic central nervous system AII hypertension in rats fed
      high sodium chloride diet from weaning.
AB  - CNS angiotensin II (AII) hypertension is induced by chronic, low dose
      intracerebroventricular (ICV) AII infusion only in rats raised on a relatively
      high sodium chloride diet (250 meq kg(-1)food) from weaning. This experimental
      model of hypertension is dependent upon renal sympathetic innervation and
      associated with neurogenic sodium retention. This study determined whether AT1
      and/or AT2 receptor subtypes in the CNS mediate this neurogenic ICV AII
      hypertension. Rats were weaned at 21 days of age and fed a 1.5% sodium chloride
      diet for 10-12 weeks. At adulthood, animals were instrumented with CNS lateral
      ventricular cannulas, femoral arterial and vein catheters and housed in metabolic
      pens for chronic study. Low dose ICV AII infusion (20 ng min(-1) )increased mean
      arterial pressure by 12+/-2 mm Hg and decreased urinary sodium excretion for
      three consecutive days. Subsequent ICV AT1 blockade with losartan abolished both
      the pressor and antinatriuretic responses to low dose ICV AII. In contrast, ICV
      AT2 receptor blockade with PD 123319 did not affect either angiotensin induced
      pressor or antinatriuretic responses. Following cessation of ICV AII infusion,
      arterial pressure and sodium excretion returned to values not significantly
      different from control in both groups of rats. These data confirm that low dose
      ICV AII causes hypertension and sodium retention in rats raised from early age on
      moderately elevated sodium intakes. This AII mediated neurogenic hypertension and
      antinatriuresis is transduced by activation of CNS AT1 receptors and not by
      activation of central AT2 receptors.

PMID- 9760077
TI  - Pharmacological properties of the CO2/H+-sensitive area in the ventral medullary
      surface assessed by the effects of chemical stimulation on respiration.
AB  - We recently discovered that CO2/H+-sensitive neurons in the ventral medullary
      surface (VMS) are immunoreactive to glutamate, glutamic acid decarboxylase (GAD),
      calcineurin and cAMP. We then tested the hypothesis that glutamate, GABA,
      calcineurin and cAMP affect the activity of CO2/H+-sensitive neurons in the VMS.
      Using male Wistar rats anesthetized with urethane and pentobarbital, we checked
      for changes in relative tidal volume (VT) and respiratory frequency (f) in
      response to injecting the VMS with a variety of test agents dissolved in mock
      CSF. Respiratory changes occurred immediately and were dose-dependent. (1) 200
      1600 pmol Glutamate increased VT but decreased f. The glutamate effect was never
      abolished by concomitant injection of AP5, a NMDA receptor antagonist, but was
      abolished by CNQX, an AMPA receptor antagonist, indicating predominance of AMPA
      receptors in the CO2/H+-sensitive neurons in the VMS. (2) 200-1600 pmol GABA
      decreased both VT and f. The GABA effect was never abolished by concomitant
      injection of saclofen, a GABA(B) receptor antagonist, but was abolished by
      bicuculline, a GABA(A) receptor antagonist, indicating predominance of GABA(A)
      receptors in the CO2/H+-sensitive neurons in the VMS. (3) 4-32 microg
      Calcineurin, a Ca2+/calmodulin-dependent protein phosphatase 2B, and 200-1600
      pmol FK506, selective inhibitor of calcineurin, had no effect on respiration when
      they were applied extracellularly, but 400-3200 pmol BAPTA-AM, an intracellular
      Ca2+-chelating agent, decreased both VT and f, indicating involvement of
      intracellular Ca2+ in the excitatory mechanisms of respiration. (4) 100-800 pmol
      IBMX, an enhancer of intracellular cAMP, decreased both VT and f, indicating
      involvement of cAMP in the inhibitory mechanisms of respiration. These results
      indicate that the CO2/H+-sensitive neurons in the VMS contain glutamate and/or
      GABA in cytoplasma, possess AMPA and/or GABA(A) receptors on surface of plasma
      membrane, and compose the internal circuit, and that their activities are
      regulated by Ca2+ and cAMP.

PMID- 9760078
TI  - Efferent projection from the rostral ventrolateral medulla to the area postrema
      in rats.
AB  - The rostral ventrolateral medulla (RVLM) is a region of the brain primarily
      involved in cardiovascular control. It receives information from several areas of
      the brainstem, among which the area postrema (AP) and the nucleus of the solitary
      tract (NTS). The medial subnuclei of the solitary tract (TS) project towards the
      RVLM, providing cardiopulmonary information, and the AP serves information about
      circulatory hormones. Although the efferent pathways are well known, it is not
      the case for the connections from the RVLM towards the AP and the NTS. The
      present study was designed to examine the efferent connections from the RVLM onto
      the dorsal structures of the medulla: quantitatively by means of anatomical
      techniques, and functionally by means of electrophysiological techniques.
      Morphologically, Biocytin or Biotinylated dextran amine microinjections into the
      RVLM were followed by labelling of many fibres running towards the bulbar
      dorsomedial structures, with some pathways lying in the AP itself, or located in
      its caudal vicinity. Conversely, when microinjections of Fast Blue (FB) were made
      into the AP, FB-labelled cells could be observed within the RVLM.
      Electrophysiologically, single shock stimulation carried on AP allowed
      identification of axonal fibres issuing from somata located into the
      cardiovascular neuronal pool in the RVLM. From these results, we can assume: (1)
      the existence of dense efferent projection from RVLM to aspects of the dorsal
      vagal complex, including the AP and, among this dense projection, (2) the
      existence of some fibres terminating in, or crossing through the AP, and
      identified as conveying baroreceptor-related information, in the rat.

PMID- 9760079
TI  - Differential effects of anesthetics on sympathetic nerve activity and arterial
      baroreceptor reflex in chronically instrumented rats.
AB  - The effects of pentobarbital sodium, chloralose, and urethane on sympathetic
      nerve activity and arterial baroreceptor reflex were examined using rats
      chronically instrumented for recordings of blood pressure (BP), electrocardiogram
      and renal sympathetic nerve activity (RSNA). Pentobarbital sodium (30 mg/kg,
      i.v.) produced a decrease in BP with a transient decrease in heart rate (HR) and
      no change in RSNA. Chloralose (50 mg/kg, i.v.) also caused a decrease in BP and
      no change in HR and RSNA until a later increase in HR and RSNA, while urethane
      (800 mg/kg, i.v.) increased BP, HR, and RSNA. Baroreceptor reflex function was
      assessed by constructing a logistic function curve compiled from data obtained by
      intravenous infusion in increasing doses of phenylephrine and sodium
      nitroprusside. Both pentobarbital sodium and chloralose administration decreased
      the gain of baroreceptor reflex control of both HR and RSNA. Urethane also
      decreased the gain of baroreceptor reflex control of HR but elicited no change in
      that of RSNA. These results suggest that different intravenously administered
      anesthetics affect the peripheral sympathetic outflows in qualitatively and
      quantitatively different manners.

PMID- 9760080
TI  - Cholinergic vasoregulation in normal and adjuvant monoarthritic rat knee joints.
AB  - The role of cholinergic nerves in joint vasomotor control was investigated in
      normal and chronically inflamed rat knees. Joint inflammation was induced by
      unilateral intraarticular injection of Freund's complete adjuvant and experiments
      were performed on both the ipsilateral and contralateral joints one and three
      weeks after treatment. Blood flow measurements of the exposed joints were
      obtained using a laser Doppler perfusion imager which provides relative changes
      in tissue perfusion. One week after adjuvant induction, basal perfusion in both
      ipsilateral and contralateral joints was significantly reduced compared to
      normal. At three weeks, ipsilateral knee perfusion had returned to normal,
      however, contralateral blood flow showed no such sign of recovery. Topical
      application of the muscarinic receptor antagonist atropine caused a fall in knee
      joint basal perfusion suggesting that cholinergic nerves are inherently involved
      in the physiological control of rat knee blood vessels. Acetylcholine chloride
      (10(-13)-10(-8) mol) in normal rats produced a dose-dependent vasodilatation of
      the articular microvasculature with the highest dose causing blood flow to
      increase by about 85%. This dilator response was attenuated in the ipsilateral
      monoarthritic joint at both one and three weeks post-injection while
      contralateral joints showed a normal response to acetylcholine at both of the
      time points tested. This study implicates cholinergic nerves in rat knee joint
      vasoregulation, however, the impairment of this mechanism by chronic inflammation
      could exacerbate the disease process by starving the joint of much needed
      vascular nourishment. Furthermore, the preservation of cholinergic responses in
      the contralateral knee despite a fall in basal perfusion suggests that
      alternative non-cholinergic mechanisms may be responsible for the hypoaemia in
      this joint.

PMID- 9760081
TI  - Presynaptic muscarinic M1 and M2 receptor modulation of auriculotemporal nerve
      transmission in the rat.
AB  - Parotid secretory and vascular responses to electrical stimulation of the
      parasympathetic innervation were measured in anaesthetized rats. Stimulation was
      performed at 1, 10 and 40 Hz. Atropine (1.5 micromol/kg i.v.) almost abolished
      the secretion to stimulation of peptide depleted nerves at 40 Hz, thus confirming
      the existence of a pure cholinergic response. Atropine also reduced secretion by
      74% during stimulation of non-depleted nerves at the same frequency. Selective
      blockade by the muscarinic M1 receptor antagonist pirenzepine and by the
      muscarinic M2 receptor antagonist methoctramine was found to occur at doses (50
      nmol/kg i.v. and of 300 nmol/kg i.v., respectively) that did not inhibit the
      responses to exogenous acetylcholine. In the presence of methoctramine, the nerve
      evoked fluid responses were increased by 200% at 1 Hz independently of the total
      number of impulses (10-300), suggesting that M2 receptor activation normally has
      an inhibitory effect on transmitter release. The magnitude of the increase was
      inversely related to frequency of stimulation, and changes in the secretory
      responses occurred at 40 Hz only when non-depleted nerves were stimulated over
      the longest period employed. The fluid response then increased by 35% and protein
      concentration by 200%. The vasodilator responses increased at 1 and 10 Hz, but
      not at 40 Hz. Pirenzepine reduced the secretory and vascular responses at 10 and
      40 Hz but only during stimulation over short periods of time. This suggests that
      M1 receptor activation normally has a facilitatory effect on neurotransmitter
      release. During stimulation of non-depleted nerves at 10 Hz for 10 impulses, the
      fluid response was reduced by 29% and the protein concentration by 26%. When the
      peptide depleted nerves were stimulated at 10 Hz, pirenzepine also reduced the
      fluid response (by 43%), but not the protein concentration. It is concluded that
      the release of transmitter from postganglionic nerve fibres in the rat
      auriculotemporal nerve is modulated by presynaptic muscarinic receptors.
      Muscarinic M1 receptors normally facilitate cholinergic and peptidergic
      transmission during short, intense stimulation. On the other hand, muscarinic M2
      receptors normally inhibit cholinergic transmission at low frequencies; at higher
      frequencies, peptidergic transmission is also inhibited, but only after some
      delay.

PMID- 9760082
TI  - Reexamination of custody restraint position and positional asphyxia.
AB  - The use of the hogtie restraint (also known as hobble or prone maximal restraint)
      by law enforcement and prehospital personnel has come under scrutiny because of
      reports of sudden deaths in persons placed in this restraint position. Some
      contend that this body position restricts chest and abdominal movement to the
      point that individuals are at risk for hypoventilatory respiratory compromise and
      "positional" asphyxiation. We review case reports of custody deaths in subjects
      placed in the hogtie position, as well as related medical literature regarding
      positional asphyxia. We also review the current research findings from human
      physiology studies that have investigated the effects of the hogtie position on
      respiratory and pulmonary function. We conclude that the hogtie restraint
      position by itself does not cause respiratory compromise to the point of
      asphyxiation and that other factors are responsible for the sudden deaths of
      individuals placed in this position.

PMID- 9760083
TI  - Vertebral artery trauma.
AB  - Vertebral artery trauma is not commonly seen by forensic pathologists. The
      experience of vertebral artery trauma at the Victorian Institute of Forensic
      Medicine (30 cases) is summarized and reviewed in the light of the literature.
      Causes of vertebral artery trauma are discussed. In case 1, the history and
      timing of the injury raise the question as to whether the vertebral artery
      dissection occurred before the episode of trauma, that is, was spontaneous or
      resulted from trauma. Moreover, underlying vertebral artery disease was present,
      raising the question as to how much trauma was needed to cause vertebral artery
      dissection. In case 2, despite the history of head/neck trauma, a neurosurgeon
      considered the subarachnoid hemorrhage was spontaneous, due most likely to
      ruptured saccular aneurysm or arteriovenous malformation. In case 3, the
      vertebral artery rupture was not diagnosed in the setting of multiple injuries.
      Case 4 is an example of prolonged survival with delayed onset of symptoms
      following vertebral artery trauma. Case 5 is an example of the not uncommon
      scenario of homicidal vertebral artery trauma accounting for basal subarachnoid
      hemorrhage, rapid collapse and death. Cases 1 and 4 indicate that relatively
      normal activity may be possible following vertebral artery trauma in some cases
      (at least for a time). Cases 1 and 4 are also examples of intracranial vertebral
      artery dissection.

PMID- 9760084
TI  - Air bag-associated injury to a child in the front passenger seat.
AB  - We report the case of a 3.5-year-old front seat passenger who suffered
      significant head and neck injuries as a result of air bag deployment in a
      collision of <30 mph. These lesions included multiple abrasions of the lower half
      of the face, nose, forehead, and right ear, torn frenula, conjunctival petechiae,
      comminuted fractures of the left and right lateral frontal regions and right
      parietal bone, diastatic fracture of the coronal suture, subgaleal and
      subarachnoid hemorrhages, cortical contusions, subluxation of the
      atlantooccipital joint, and fracture of the C4 vertebral body. These lesions are
      consistent with trauma secondary to the deploying air bag and the head striking
      the interior of the car. The findings in this case further support the Centers
      for Disease Control and Prevention (CDC) guidelines of keeping children properly
      restrained, preferably in the back seat, or as far as possible from air bags.

PMID- 9760085
TI  - Problems in the interpretation of hemorrhage into neck musculature in cases of
      drowning.
AB  - To investigate the possible causes of unexplained hemorrhage into the neck
      musculature in deaths due to drowning, all cases of drowning between the years
      1985 and 1995 examined by members of the Department of Forensic Pathology,
      University of Sheffield were reviewed. Cases were selected in which hemorrhage
      was found within the neck musculature but in which no apparent explanation for
      the hemorrhage, such as compression of the neck or trauma, was present. Eight
      cases were identified from a total of 99 deaths from drowning. Postmortem
      hypostasis was distributed in the back or diffusely in 6 cases and in the face in
      3 cases. The degree of decomposition varied but was severe in only 1 case. A
      raised blood alcohol level was detected in 3 cases. Anterior neck compartment
      hemorrhage is probably due to hypostasis in a high proportion of cases. The
      Prinsloo and Gordon artifact may be an operative factor in at least some cases.
      Hemorrhage may result from violent neck movements during the process of drowning.
      Apparent "bruising" of the neck musculature does not always indicate compression
      of or trauma to the neck.

PMID- 9760086
TI  - Injury patterns in a plastic (AR-1) baton fatality.
AB  - Rubber and plastic bullets or batons have been used in countries outside the
      United States for several years. These devices were designed to inflict nonlethal
      force in riot control. The authors report a case of fatal injury sustained by an
      elderly woman struck in the chest by a plastic baton, including the circumstances
      surrounding this unusual incident, the autopsy findings and a review of the
      literature.

PMID- 9760087
TI  - A penny (or peso) for your thoughts: an unusual intermediate target.
AB  - Intermediate targets becoming secondary projectiles in gunshot wounds is a well
      recognized phenomenon. Secondary projectiles usually possess a fraction of the
      kinetic energy compared to the primary projectile, leading to superficial wounds
      of skin and soft tissue. We describe the case of a foreign object that was
      propelled by the primary bullet with sufficient energy to penetrate not only skin
      and soft tissue, but also temporal skull and brain. The report also examines the
      energy requirements for an object to penetrate bone and unique radiographic
      findings.

PMID- 9760088
TI  - Toward an electronic death registration system in the United States: report of
      the Steering Committee to Reengineer the Death Registration Process.

PMID- 9760089
TI  - Forensic science program: a community effort.
AB  - A forensic science program has been developed to assist the professional
      community population in using a scientific approach in the investigation of
      criminal offenses. The science of medicine and the principles of the law come
      together to form a multidisciplinary group of professionals to instruct in the
      collection of evidence after a crime has been committed. Specialists in these
      areas include forensic pathologists, forensic anthropologists, forensic
      odontologists, entomologists, and a radiologist with a specialty in forensics. No
      longer can educators ignore the necessity of community involvement in the
      apprehension and prosecution of the perpetrators of crime. This program is the
      first to offer basic forensic science courses to professionals in a variety of
      related fields.

PMID- 9760090
TI  - The Abbreviated Injury Scale: application to autopsy data.
AB  - Twenty autopsy reports, comprising 1 fall, 1 cutting, 1 burn, 1 drowning, 1
      strangulation, 3 gunshot wound, and 13 traffic fatalities, were scored by the
      Abbreviated Injury Scale (AIS) and the Injury Severity Score (ISS). The codes
      were adequate for wounds of skin and long bones, and for most wounds of viscera.
      The autopsy descriptions were more detailed than the coding criteria for
      craniocerebral, cervicovertebral and muscular trauma, and less detailed for
      thoracoabdominal visceral, and long bone trauma. Lung contusions and rib
      fractures received scores that seemed unduly high, possibly reflecting the
      greater sensitivity of autopsy diagnosis over clinical diagnosis for these
      lesions. Complete hinge fractures of the skull base scored 4 (severe), which does
      not reflect the almost universally lethal nature of the accompanying cerebral
      concussion, which was itself not codeable. AIS scores were low and did not seem
      to reflect the lethal outcome when the lethal mechanism was purely physiologic
      and without a striking morphologic derangement, as in instances of cerebral or
      cardiac concussion, compression of the neck, occlusive airway hemorrhage, and
      visceral herniation into an adjacent body cavity. The scores were similarly low
      when therapy was delayed or adverse. Low AIS and ISS scores in a fatality from
      blunt or penetrating trauma may be useful retrospective clues to the presence of
      purely physiologic death mechanisms or therapeutic problems.

PMID- 9760091
TI  - Sudden death due to intravenous infusion of hair conditioner.
AB  - A case of sudden death in a 14-year-old girl due to self administration of hair
      conditioner through an intravenous infusion pump is described. This report
      demonstrates difficulties that may occur in determining the manner of death in
      such cases and outlines a specific danger that may occur when adolescents have
      unsupervised access to intravenous infusion equipment.

PMID- 9760092
TI  - Inadvertent intrathecal administration of potassium chloride during routine
      spinal anesthesia: case report.
AB  - During routine spinal anesthesia, an ampule of potassium chloride, instead of
      bupivacaine, was mistakenly opened and inadvertently administered intrathecally
      to a patient, resulting in pain, cramps, and death within 2.5 hours of injection.
      We discuss the medicolegal implications of such an error and possible preventive
      measures pertaining to this case.

PMID- 9760093
TI  - Acute coronary artery thrombosis in a postpartum woman receiving bromocriptine.
AB  - A 35-year-old postpartum woman who was receiving bromocriptine (Parlodel) for
      only several days to suppress lactation experienced an episode of a seizure,
      complained of chest pains, and died in the emergency department. At autopsy,
      acute coronary thrombosis of the left main, left anterior descending, and
      circumflex arteries was found. Cases of reported cardiac-related complications
      associated with bromocriptine use in the puerperium are extremely rare. The
      mechanism of bromocriptine-related acute coronary thrombosis is poorly understood
      and warrants further scrutiny, because the synthetic brominated ergopeptide is
      generally regarded as safe. The updated review of reports available in literature
      mandates the acknowledgment of possible serious and even lethal cardiac events as
      a result of untoward effects of bromocriptine.

PMID- 9760095
TI  - Pericardial fluid postmortem: Comparative study of natural and violent deaths.
AB  - Thanatochemistry is an increasingly important ancillary procedure in forensic
      practice. Alterations are known to take place in biochemical components during
      the postmortem period, particularly in the blood, and both research results and
      their interpretation have been the object of some controversy. For that reason,
      emphasis has been placed on the examination of fluids that are neither altered
      nor contaminated as rapidly as blood after death. This study tested the
      hypothesis that pericardial fluid (PF) may be a suitable medium for biochemical
      analysis in corpses. The study sought to determine concentrations of urea,
      creatinine, glucose, creatinine kinase 2, proteins, calcium, sodium, and
      potassium, in the pericardial fluid of corpses. The study sample was divided into
      two groups, natural deaths and violent deaths. Intergroup results were compared,
      using Mann-Whitney's U test for paired data. No significant differences were
      obtained between the natural death and violent death groups for the parameters
      studied, with the exception of urea (p < .05). Further studies are required to
      compare these results and create the possibility for new conclusions.

PMID- 9760094
TI  - Amphetamine derivative fatalities in South Australia--is "Ecstasy" the culprit?
AB  - OBJECTIVE: To analyze features of a series of fatalities caused by amphetamine
      derivative designer drugs marketed as "Ecstasy" in South Australia, and to
      identify reasons for the recent marked increase in number of these deaths.
      MATERIALS AND METHODS: Following the death of a 26-year-old woman after alleged
      ingestion of Ecstasy tablets, a retrospective search of files at State Forensic
      Science, Adelaide and the South Australian State Coroner's Department was
      undertaken from February 1992 to January 1997 to identify similar cases. RESULTS:
      Six fatalities were found, all of which have occurred since September 1995 (M:F
      ratio, 1:1; age range, 22 to 36 years; average age, 27.7 years). All individuals
      had histories of recent ingestion of illegal drugs thought to be Ecstasy
      (methylenedioxymethamphetamine, MDMA) at the time of purchase. Delay occurred in
      seeking medical attention, despite severe symptoms. Causes of death involved
      documented hyperthermia in 3 cases (temperatures of 41.5-46.1 degrees C), with
      features of hyperthermia in one other case, and intracranial hemorrhage in
      another. Drugs in toxic/lethal amounts identified at postmortem included
      paramethoxyamphetamine (PMA) in all cases, amphetamine/methamphetamine in 4
      cases, and methylenedioxymethamphetamine (MDMA or Ecstasy) in only 2 cases.
      Interaction with a prescription medication (fluoxetine) may have occurred in 1
      case. CONCLUSIONS: The number of deaths due to amphetamine derivatives apparently
      due to substitution of PMA for MDMA (Ecstasy) have recently increased markedly in
      Adelaide. Potential users should be warned that PMA has been associated with a
      much higher rate of lethal complications than other designer drugs, and that no
      guarantee can be made that tablets sold as Ecstasy are not PMA.

PMID- 9760096
TI  - Automated coding of injuries from autopsy reports.
AB  - Medical examiners have a unique database about trauma victims, many, if not most,
      of whom died at the scene or in transit to a hospital and who, thus, never had
      their injuries documented by trauma surgeons and so never entered into a local or
      regional trauma registry. These trauma registries have assisted in assessing the
      magnitude of traumatic injuries in the community and in evaluating the
      community's emergency medical systems. Without information about those who are
      dead at the scene or who die in transit, these trauma registries are incomplete
      and the evaluations based on them inaccurate. The data about the 50% of trauma
      victims who never enter the medical system are lacking in these registries. Such
      information is present in the death investigation and autopsy reports in the
      various medical examiner/coroner offices in the country. To access this important
      information more easily in trauma registries, an expert computer system was
      developed. This pilot study presents the results of using that system to gather
      medical examiner data. Injury descriptions were abstracted from autopsy reports
      of 50 consecutive nonhospitalized persons fatally injured in Mobile County,
      Alabama and its environs. Injury descriptions for all cases were successfully
      coded in International Classification of Disease, 9th Revision, Clinical
      Modification (ICD-9-CM) and the Abbreviated Injury Scale (AIS-90) by an expert
      system. For some cases the expert system "requested" and received clarifying
      information, all of which was present in the medical records. This research
      demonstrates the feasibility of gathering accurate and consistent information on
      the estimated 50% of trauma deaths who do not reach a hospital and who are not
      included in acute care registries. Without data on such patients, our evaluation
      of trauma systems is incomplete and resources directed at prevention and
      treatment may be misapplied.

PMID- 9760097
TI  - Murder-suicide in central Virginia: a descriptive epidemiologic study and empiric
      validation of the Hanzlick-Koponen typology.
AB  - An empiric validation of a proposed typology of murder-suicide events was carried
      out in the Central District of the Office of the Chief Medical Examiner of
      Virginia for two cohorts, 1980 to 1984 and 1990 to 1994; use of a single typology
      allows description of trends in these events over time, a unique aspect of this
      study. For both cohorts, a total of 53 successful events with 63 victims (116
      total deaths) was evaluated. A significant shift in the characteristics of
      location, perpetrators, and victimology of such events between the two cohorts is
      demonstrated: events changed from urban, multiple victim events with a majority
      of white perpetrators to rural, dyadic events in which victims did not live with
      perpetrators, the majority of whom were black. The results are compared with
      published data, and the implications for use of this typology as a clinical
      evaluation tool for prevention are addressed in light of current domestic
      violence emphases in public health. Additionally, the need for prospective
      tracking of these events is reiterated and use of the Hanzlick-Koponen typology
      as the tool for such tracking is suggested.

PMID- 9760098
TI  - Rate of aspartic acid racemization in bone.
AB  - There are no reports on rates of amino acid racemization in bones. To investigate
      the possibility of estimating age by evaluating amino acid residue racemization
      in human bones, a heating experiment was performed and the rate of aspartic acid
      racemization was determined using the Arrhenius equation. Assuming an annual mean
      temperature of 15 degrees C, the rate constant (k) for aspartic acid racemization
      in bone was calculated, and the racemization rate at 15 degrees C k (y) was
      4.1036 x 10(-9)--much lower than that of dentin. These results suggest that it is
      more difficult to accurately determine age by analyzing aspartic acid residues in
      bone than in dentin.

PMID- 9760099
TI  - The perfect crime: myth or reality?
AB  - The primum movens of a forensic autopsy is to track down the crime. The perfect
      crime can be defined as one which will never be suspected and/or one for which
      the criminal will never be arrested. We have reported several cases that have
      been adjudicated or are being adjudicated, and we show how actual homicides could
      have been taken for accidental deaths, suicides, or even natural deaths.

PMID- 9760100
TI  - Fatty liver in sudden infant death autopsies.

PMID- 9760101
TI  - Homicidal poisoning by paraquat.

PMID- 9760102
TI  - Nociceptin/orphanin FQ. A new opioid, a new analgesic?
AB  - Opioids form the major class of strong analgesics. Endogenous opioids and their
      receptors play important roles in central nervous system function. Thus, the
      discovery of a new opioid peptide, nociceptin or orphanin FQ, and its receptor,
      opioid receptor-like 1 (ORL-1) has caused considerable interest since this
      transmitter system appears to exhibit a number of key differences to the other
      opioids. Analgesia can be produced at spinal sites but there is compelling
      evidence that the peptide may also have 'anti-opioid' actions in the brain.
      Effects on auditory processing, pains from nerve injury coupled with an apparent
      lack of motivational effects have important implications for novel therapy. This
      review surveys the recent functional studies on this novel peptide.

PMID- 9760103
TI  - Effect of 7-nitroindazole on body temperature and methamphetamine-induced
      dopamine toxicity.
AB  - The present study was undertaken to examine the role of temperature on the
      ability of 7-nitroindazole (7-NI) to prevent methamphetamine-induced dopamine
      (DA) neurotoxicity. Male Swiss-Webster mice received methamphetamine alone or in
      combination with 7-NI at either room temperature (20+/-1 degrees C) or at 28+/-1
      degrees C. At 20+/-1 degrees C, 7-NI produced hypothermic effects and afforded
      total protection against methamphetamine-induced DA depletions in the striatum.
      At 28+/-1 degrees C, 7-NI produced minimal effects on body temperature and failed
      to prevent methamphetamine-induced DA reductions. These findings indicate that
      the neuroprotection afforded by 7-NI is likely related to its ability to produce
      hypothermia because agents that produce hypothermia and/or prevent hyperthermia
      are known to attenuate methamphetamine-induced neurotoxicity.

PMID- 9760104
TI  - Unspecific long-term potentiation can evoke functional segregation in a model of
      area 17.
AB  - It has been shown recently in rat hippocampus that the synapse specificity of
      Hebbian long-term potentiation breaks down at short distances (< 100 microm).
      Using a neural network model we show that this unspecific component of long-term
      potentiation can be responsible for the robust formation and maintainance of
      cortical organization during activity-driven development. When the model is
      applied to the formation of orientation and ocular dominance in visual cortex,
      addition of an unspecific component to standard Hebbian learning, in combination
      with a tendency of left-eye and right-eye driven synapses to initially group
      together on the postsynaptic neuron, induces the simultaneous emergence and
      stabilization of ocular dominance and of segregated, oriented ON/OFF subfields.
      Since standard Hebbian learning cannot account for the simultaneous stabilization
      of both structures, unspecific LTP thus induces a qualitatively new behaviour.
      Since unspecific LTP only acts between synapses which are locally clustered in
      space, our results imply that details of the local grouping of synapses on the
      dendritic arbors of postsynaptic cells can considerably influence the formation
      of the cortical functional organization at the systems level.

PMID- 9760105
TI  - Nociception activates Elk-1 and Sap1a following expression of the ORL1 receptor
      in Chinese hamster ovary cells.
AB  - Nociceptin stimulation of the ORL1 receptor expressed in Chinese hamster ovary
      (CHO) cells results in the activation of the extracellular signal regulated
      kinases ERK1 and ERK2. ERK1/ERK2 activation is inhibited by pertussis toxin, the
      MEK inhibitor PD 98059 and by transient expression of alpha-transducin,
      indicating that ORL1 up-regulation of these kinases occurs as a consequence of
      the release of the G-protein betagamma complex following the activation of
      pertussis-toxin sensitive Galphai-family G-proteins. Using specific reporter
      genes we demonstrate that the transcription factors Elk-1 and Sapla are activated
      in a pertussis toxin-sensitive manner as a consequence of ORL1 upregulation of
      ERK1/ERK2 to induce changes in gene expression. The activation of these
      transcription factors is also inhibited following treatment with PD 98059 and
      following coexpression of alpha-transducin.

PMID- 9760106
TI  - Mismatch negativity (MMN) as an index of auditory sensory memory deficit in cleft
      palate and CATCH syndrome children.
AB  - Our recent study demonstrated with the brain's automatic change-detection
      response, the mismatch negativity (MMN) of the event-related potentials (ERPs),
      that the duration of auditory sensory memory is significantly shorter in school
      age children with CATCH syndrome than in healthy age-matched controls. One of the
      characteristic symptoms of this syndrome, caused by a microdelection in
      chromosome 22, is cleft palate. The most common problems in these children,
      however, are learning difficulties and, according to our results, it is likely
      that these problems are not due to the dysmorphology of peripheral speech
      mechanisms only but are also caused by CNS dysfunctions. In the present study we
      show with MMN that auditory sensory memory is also shortened in school-age
      children with cleft palate but without the CATCH syndrome. It has been shown in
      previous studies with neuropsychological tests that although children with cleft
      palate have language and learning-related problems these difficulties are usually
      less severe than those of CATCH children. Likewise the present study demonstrates
      that the auditory sensory memory trace seems to decay more rapidly in CATCH
      children than in children with cleft palate.

PMID- 9760108
TI  - Abnormal mushroom body plasticity in the Drosophila memory mutant amnesiac.
AB  - In Drosophila melanogaster, adult or larval rearing conditions influence brain
      structure. In particular, larval density affects the number of fibers forming the
      mushroom bodies, a neuropil structure involved in olfactory learning. The
      mushroom bodies receive chemosensory inputs from the antennal lobes at the level
      of the calyx. In this study we report that larval density affects calyx volume
      measured shortly after eclosion from the pupal case. We observe that in the
      memory mutant amnesiac this form of experience-dependent structural plasticity is
      missing, whereas it is not affected in the learning mutant rutabaga and in the
      memory mutant radish. Independent of the plasticity effect, the calyces are on
      average slightly bigger than wild type in amnesiac and smaller in rutabaga flies.

PMID- 9760107
TI  - NPY Y1 receptors in the dorsal periaqueductal gray matter regulate anxiety in the
      social interaction test.
AB  - We have reported previously that the NPY Y1 receptor antagonist BIBP3226 applied
      into the dorsal periaqueductal gray matter (DPAG) has an anxiogenic-like effect
      in the elevated plus-maze test in rats. In the present study the effects of
      neuropeptide Y (NPY) Y1 receptor antagonists BIBP3226 (500 pmol) and 1229U91
      (formerly also GR231118, GW1229 and EXBP68, 100 and 500 pmol) administered into
      the DPAG were investigated in the social interaction test in rats. BIBP3226 and
      1229U91 (both 500 pmol) significantly decreased the time spent in active social
      interaction. These results provide additional evidence that NPY-ergic
      neurotransmission in the DPAG may be involved in the modulation of anxiety
      related behaviour and suggest that endogenous NPY, released under stressful
      conditions in the DPAG, relieves anxiety via the NPY Y1 receptors. This is the
      first report demonstrating the effect of NPY receptor active agent on social
      behaviour.

PMID- 9760109
TI  - Failure of localized head cooling to reduce brain temperature in adult humans.
AB  - Non-invasive brain temperature measurements using proton magnetic resonance
      spectroscopy were used to test the hypothesis that localized head cooling would
      reduce brain temperature in 10 normal adult humans. Temperature reductions of the
      head surface to 15.8+/-3.5 degrees C did not reduce brain temperature measured in
      the superficial cortex (36.8+/-0.5 degrees C) or thalamus (36.6+/-0.7 degrees C),
      as compared to measurements obtained with a head surface temperature of 34.7+/
      1.6 degrees C (37.0+/-0.6 degrees C and 36.6+/-0.4 degrees C, respectively).
      There was no change in the temperature gradient from the superficial to deep
      brain locations in the presence or absence of head cooling, and brain temperature
      did not decrease as a function of the duration of head cooling for periods up to
      50 min. There was no correlation between the scalp surface (range: 10-38 degrees
      C) and brain temperature at either the deep or superficial locations.

PMID- 9760110
TI  - Kv1.1 channel antisense attenuates learning and modulation of dentate
      polysialylated NCAM.
AB  - The distribution and modulation of neural cell adhesion molecule polysialylation
      state (NCAM PSA) and the consequence of antisense inactivation of the Kv1.1
      potassium channel was investigated following avoidance learning in mice. PSA
      immunoreactivity was most notable on cells at the inner denate border and in
      cortical layer II. Task acquisition resulted in a significant 30% transient
      increase in the frequency of dentate polysialylated neurons at the 12 h post
      training time. In contrast, animals pretreated with the Kv1.1 antisense
      oligonucleotide exhibited both attenuated recall avoidance latencies and
      polysialylated cell frequency. As Kv1.1 is enriched on the dendrites of these
      granule-like cells, the attenuated polysialylation response is considered
      secondary to NCAM-mediated events during their transient synapse production in
      the 6-8 h post-training period.

PMID- 9760111
TI  - Attenuation of c-Fos basal expression in the cerebral cortex of aged rat.
AB  - Cellular immediate early genes (IEG) such as c-fos were originally defined as
      rapid and transient inducible gene, but their products show a varying degree of
      basal expression in the brain of normal animals, suggesting that they also play a
      role in the transcriptional control under physiological conditions. In this
      study, we used an immunohistochemical method to investigate changes in the number
      of c-Fos-immunoreactive cells in the cerebral cortex and hippocampal formation of
      the aged rat. There was a remarkable decrease in the number of c-Fos
      immunoreactive cells in the piriform and temporal cortex of aged rats compared
      with young adult rats. There was a slight decrease in the number of c-Fos
      immunoreactive cells in the parietal cortex of aged rat. In the hippocampal
      complex, there were also decreases in the number of c-Fos-immunoreactive cells in
      aged rat; the degree of decrease was most prominent in the dentate gyrus. This
      report provides the first morphological evidence for decreased levels of basal c
      Fos expression in some cerebral cortical areas and in the hippocampal complex of
      aged rats.

PMID- 9760112
TI  - Presynaptic modulation of Lymnaea neurons evoked by computer-generated spike
      trains.
AB  - To investigate the functional organisation and information processing in Lymnaea
      neuronal networks, artificial spike trains were elicited in one of the main
      respiratory interneurons (RPeD1) and the modulation of the firing patterns of
      postsynaptic cells was examined. This was performed by precisely timing the
      action potential generation of the presynaptic cell using a computer-controlled
      voltage clamp amplifier (pattern clamp technique). Induced oscillation (0.1-0.4
      Hz) in the firing pattern of RPeD1 spread to a large number of postsynaptic
      cells, as clearly demonstrated by Fourier power spectra. At the same time, no
      signs of precise (millisecond) spike timing was observed in the cells studied.
      The results confirm that the neurons used in our experiments process information
      as pure rate-coders.

PMID- 9760113
TI  - Partial cloning and distribution of estrogen receptor beta in the avian brain.
AB  - A partial estrogen receptor beta (ER-beta) cDNA was isolated from testicular
      quail RNA by RT-PCR with degenerate primers specific to the rat ER-beta sequence.
      A high expression of ER-beta was demonstrated by RT-PCR in the telencephalon,
      diencephalon, pituitary, testis and kidneys of male quail but little or no
      expression was detected in the cerebellum, pectoral muscle and adrenal gland. In
      situ hybridization with a 35S-labelled oligoprobe in sections through the
      preoptic area-rostral hypothalamus identified high expression in the medial
      preoptic nucleus, bed nucleus striae terminalis and nucleus taeniae. These data
      demonstrate the presence of an ER-beta in brain areas implicated in the control
      of reproduction in a non-mammalian species.

PMID- 9760114
TI  - Immunohistochemical localization of redox factor-1 (Ref-1) in Alzheimer's
      hippocampus.
AB  - Redox factor-1 (Ref-1) is a dual-function protein involved in both DNA repair and
      transcriptional regulation. Ref-1 is modulated by cerebral ischemia and other
      oxidative stressors, and also regulates the DNA-binding activities of
      transcription factors implicated in Alzheimer's disease (AD)-related
      neurodegeneration. The present study examined Ref-1 expression in the AD
      hippocampus by immunohistochemistry. Although Ref-1 immunostaining was relatively
      low in control brain sections, senile plaques and other plaque-like structures in
      the AD brain were Ref-1-positive. Cells with increased Ref-1 immunoreactivity
      were also observed in regions of neuronal injury. These results suggest that Ref
      1 might contribute to senile plaque formation, and that overexpression of Ref-1
      in injured neurons may be part of a response to oxidative stress and an attempt
      to repair damaged DNA in AD.

PMID- 9760115
TI  - Alpha and beta subunits of CaM-kinase II are localized in different neurons in
      chick ciliary ganglion.
AB  - The ciliary ganglion of the chicken contains only two types of neurons. Using
      monoclonal antibodies against the alpha and the beta subunits of Ca2+/calmodulin
      stimulated protein kinase II (CaMPK-II) we found that the alpha-subunit was
      localized to the choroid neurons while beta subunit was associated with the
      ciliary neurons. As both neurons receive their inputs from the oculomotor nerve,
      while their postganglionic axons leave via different nerves, the ciliary ganglion
      of the chicken is a neuronal system in which the functional differences between
      alpha and beta CaMPK-II homopolymers in the regulation of synaptic transmission
      can be investigated.

PMID- 9760116
TI  - Multiple classes of the oligodendrocyte lineage are highly vulnerable to
      excitotoxicity.
AB  - We have recently shown that galactocerebroside (Gal-C)-expressing
      oligodendrocytes are highly vulnerable to (AMPA)/kainate receptor-mediated death.
      Here we examined the vulnerability of cells at different developmental stages of
      the oligodendrocyte lineage to AMPA/kainate receptor-mediated excitotoxicity.
      Oligodendrocyte precursor cells, pre-oligodendrocytes and mature oligodendrocytes
      were killed by 24 h exposures to low concentrations of kainate (30-100 microM).
      Death was attenuated by the AMPA/kainate receptor antagonist 6-nitro-7
      sulfamoylbenzo(f)quinoxaline-2,3-dione (NBQX). The high vulnerability of
      oligodendrocytes and their precursors to AMPA/kainate receptor excitotoxicity may
      represent an important mechanism of white matter damage resulting from trauma or
      ischemia in the perinatal and adult central nervous system (CNS).

PMID- 9760117
TI  - CCK-8 inhibits ingestive behavior in rats with lateral hypothalamic 6-OHDA
      lesions.
AB  - Male rats were injected with 6-hydroxydopamine in the lateral hypothalamus and
      tested for ingestive behavior starting on the day after the injection. The rats
      did not eat food pellets but readily ingested an intraorally infused nutritive
      solution. If given three daily intraoral infusions, 6-hydroxydopamine-treated
      rats defended their body weight and were as sensitive to the inhibitory effect of
      cholecystokinin octapeptide on intake as controls. Dopamine was reduced by 94% in
      the dorsal striatum five days after the 6-hydroxydopamine injection.
      Noradrenaline and serotonin were less markedly affected. Thus, while appetitive
      ingestive behavior is disrupted, consummatory ingestive behavior and body weight
      regulatory competence are only marginally affected by massive damage to forebrain
      dopamine neural networks.

PMID- 9760118
TI  - Purification of bovine P2 myelin protein with bound lipids.
AB  - The P2 protein is a neuritogenic, small basic protein present in PNS myelin. It
      belongs to the family of the cytoplasmic lipid-binding proteins and can be
      incorporated in lipidic bilayers. P2 has been purified and crystallized only in
      the lipid-free form. Here we show that the P2 protein can be purified with bound
      lipids by applying to PNS myelin the same procedure that as used to purify lipid
      bound myelin basic protein from CNS myelin. SDS-PAGE showed a single band of 16.5
      kDa, and TLC showed the presence of most of the myelin lipids associated with the
      protein. Lipid-bound P2 revealed different circular dichroism spectra from the
      corresponding lipid-free form, indicating that lipids influence P2 conformation.

PMID- 9760119
TI  - Rapid actions of insulin on sensory nerve function.
AB  - The acute action of insulin on neurogenic flare was investigated using
      iontophoresis. Twenty-five patients with insulin-dependent diabetes mellitus
      (IDDM) and 25 age- and gender-matched controls were studied. Axon reflex
      vasodilatation was evoked by transdermal iontophoresis of acetylcholine (ACh)
      before and after skin treatment by the iontophoresis of insulin and measured
      using laser Doppler velocimetry. Axon reflex responses were reduced in IDDM
      patients compared with controls (p< 0.001) but were restored after the
      iontophoresis of insulin. Insulin iontophoresis had no effect on the size of the
      axon reflex response in control subjects (p > 0.05). This study confirms the
      reduction of the ACh-induced flare in human patients with IDDM and has
      demonstrated relatively rapid effects of insulin on this cutaneous neurogenic
      response.

PMID- 9760121
TI  - Development of glycinergic transmission in organotypic cultures from auditory
      brain stem.
AB  - We investigated whether glycinergic transmission develops organotypically in
      auditory brain stem cultures. Slices of the medial nucleus of the trapezoid body
      and the lateral superior olive were incubated in medium with a raised
      extracellular K+ concentration. As in vivo, glycine receptor alpha1 subunit
      immunoreactivity increased and became clustered on somata and proximal dendrites.
      Together with organotypic expression of glycine transporter GLYT2, this indicates
      that molecular components of glycinergic synapses form properly. In contrast,
      glycinergic synaptic currents did not develop as in vivo: after 7 days in vitro
      they were still similar to those at the time of culture preparation. We suggest
      that for organotypic development of glycine receptors and transporters, Ca2+
      influx due to elevated K+ is sufficient. The development of functional synaptic
      transmission, however, may require patterned electrical activity.

PMID- 9760120
TI  - Secondary inhibition of 2-ketoglutarate dehydrogenase complex by MPTP.
AB  - The parkinsonism-inducing neurotoxin 1-methyl-4-phenylpyridine (MPP+) acts
      through inhibition of complex I of the electron transport chain. Recent evidence
      suggests that it may also act through inhibition of 2-ketoglutarate dehydrogenase
      complex (KDHC). We confirmed this observation in isolated rat liver mitochondria
      but found that this inhibition is prevented by preincubation with the radical
      quencher, cysteine (Cys). KDHC is also inhibited by the NO generator S-nitroso-N
      acetyl-penicillamine (SNAP) and this inhibition is similarly blocked by cysteine.
      MPP+ may inhibit KDHC secondary through a radical-mediated event rather than
      through direct interaction with KDHC.

PMID- 9760122
TI  - Tissue-type plasminogen activator is not required for kainate-induced motoneuron
      death in vitro.
AB  - Spinal motoneurons are highly vulnerable to kainate both in vivo and in vitro.
      Tissue-type plasminogen activator (tPA) and plasmin have recently been shown to
      mediate kainate-induced neuronal death in the mouse hippocampus in vivo. The aim
      of the present study was to determine whether tPA also mediates the kainate
      induced death of motoneurons in vitro. A motoneuron-enriched neuronal population
      was isolated from the ventral spinal cord of wild-type (WT) and tPA-deficient
      (tPA-/-) mouse embryos. WT and tPA-/- neurons were cultured on WT and tPA-/-
      spinal glial feeder layers, respectively. WT and tPA-/- co-cultures were
      morphologically indistinguishable. Expression of tPA in WT co-cultures was
      demonstrated using RT-PCR. WT and tPA-/- co-cultures were exposed to kainate for
      24 h. The neurotoxic effect of kainate did not differ significantly between WT
      and tPA-/- cultures. The plasmin inhibitor alpha2-antiplasmin did not protect WT
      neurons against kainate-induced injury. These results indicate that the plasmin
      system is not a universal mediator of kainate-induced excitotoxicity.

PMID- 9760123
TI  - Widespread programmed cell death in early developing chick optic tectum.
AB  - We demonstrate that widespread programmed cell death exists in proliferative
      regions of chicken optic tectum during early development using a sensitive
      fluorescent ISEL method (FISEL+) and antibody staining for an antigen in dying
      cells. Several developmental stages from embryonic day (E) 3 to E18 were
      examined. FISEL+-positive cells were rare before E7 and between E9 to E12.
      However, massive labeling was observed in the ventricular zone (VZ) between
      stages E7.5 and E8. At this time extensive cell migration is underway and many
      labeled cells were found not only in the VZ (premigratory cells) but also in the
      intermediate zone and tectal plate (migratory cells). Many labeled cells were
      also found in upper tectal laminae at late developmental stages (E15 and E18).

PMID- 9760124
TI  - Sex differences in brain regions activated by grammatical and reading tasks.
AB  - Do the brains of men and women show similar patterns of functional organization
      for language, or are men more strongly lateralized? We used PET to measure
      cerebral blood flow (CBF) as men and women read real and nonce verbs, and
      produced past tense forms. While the overall patterns of reaction time, error,
      and brain activation were similar, there were also significant sex-related
      differences in CBF patterns. During the past tense generation tasks, men showed
      left-lateralized activation while women recruited bilateral perisylvian cortex,
      confirming differences in functional laterality. During all tasks, women showed
      higher activation in occipital and/or cerebellar regions, suggesting differences
      in basic reading strategies. We conclude that sex differences in functional
      cortical organization exist in the absence of significant behavioral differences.

PMID- 9760125
TI  - Infusion of GDNF into the cerebral spinal fluid through two different routes:
      effects on body weight and corticospinal neuron survival.
AB  - Survival of axotomized adult rat corticospinal neurons (CSN) is supported by
      glial cell line-derived neurotrophic factor (GDNF). We have evaluated the trophic
      effects of intrathecally applied GDNF on CSN survival and rat body weight. Body
      weight reduction is the major side effect of intracerebral neurotrophic factor
      treatment. GDNF was tested at total doses of 30, 100 and 300 microg over 7 days
      after axotomy via different application routes: intracerebroventricularly
      (i.c.v.) and cisternally (cis). Animals injected i.c.v. displayed severe body
      weight reduction at all doses tested but CSN rescue only at the highest dose. In
      contrast, cis-infusion of GDNF promoted CSN survival at all doses and only the
      highest dose reduced the body weight. These results show that intracisternal, but
      not i.c.v., GDNF infusion at low doses can promote CSN survival without
      negatively affecting rat body weight. This finding may have implications for the
      clinic use of GDNF.

PMID- 9760126
TI  - Lazaroid-enhanced survival of grafted dopamine neurons does not increase target
      innervation.
AB  - The lazaroid U-74006F enhances survival of grafted ventral mesencephalic neurons.
      In this study the intraocular grafting model was used and survival and outgrowth
      from fetal ventral mesencephalic grafts treated with U-74006F was evaluated in
      nigrostriatal co-grafts. Fetal lateral ganglionic eminence was implanted into the
      anterior eye chamber and left to mature. Fetal ventral mesencephalon was then
      implanted and the eyes were treated with U-74006F. The lazaroid treatment
      enhanced survival of tyrosine hydroxylase (TH)-positive neurons, but did not
      enhance TH-positive nerve fiber growth into the striatal portions of the co
      grafts. However, a marked increase in nerve fiber formation was found within the
      ventral mesencephalic grafts. In conclusion, increased cell survival enhanced
      nerve fiber formation within the ventral mesencephalic portion of the co-graft
      and not, as expected, in the striatal part.

PMID- 9760127
TI  - Neuropathological findings after intracerebral implantation of microdialysis
      catheters.
AB  - The neuropathological and immunocytochemical changes in the sheep forebrain
      following 7 days of microdialysis, using a catheter approved for human use, are
      described. There was no behavioural dysfunction and light microscopy revealed
      mild astrogliosis and patchy macrophage infiltration immediately adjacent to the
      catheter track. The surrounding neuropil was normal. There was one small
      subcortical haemorrhage (10 x 1.5 mm). These findings are similar to those
      following microdialysis in rodents and suggest that the risk of significant
      damage to the human brain is low, that neuropathological changes in the brain
      around the catheter should not interfere with local brain metabolism, and that
      the catheter should be affixed in such a way as to minimize movement-induced
      damage to the brain.

PMID- 9760128
TI  - Prosaptide prevents hyperalgesia and reduces peripheral TNFR1 expression
      following TNF-alpha nerve injection.
AB  - This study demonstrated that hyperalgesia resulting from an intraneural injection
      of the cytokine tumor necrosis factor-alpha (TNF) was prevented by preemptive
      administration of a single dose of the prosaptide TX14(A) (200 microg/kg).
      TX14(A) is a synthetic 14-mer peptide with neurotrophic and cytoprotective
      activities. Efforts to elucidate TX14(A) antagonism of hyperalgesia concentrated
      on determining the effect of TX14(A) on the up-regulation of the 55 kDa TNF
      receptor (TNFR1) at the nerve injury site. It has been previously shown that
      TNFR1 expression is upregulated following nerve injury and parallels the display
      of nociceptive behavior. In our experiments, TNFR1 was decreased at the TNF nerve
      injection site in TX14(A)-treated rats when compared to vehicle-treated or
      control peptide-treated rats. Light microscopic evaluation of nerve injury site
      tissue displayed qualitatively similar neuropathology in both treatment groups
      during the time of peak hyperalgesia (day 3), but appeared more normal than
      untreated nerves at day 7 (histological scoring, mean +/-s.d., 3.7+/-0.57 for
      TX14(A)-treated and 5.67+/-0.5 for control peptide-treated). These results
      suggest that TX14(A) decreased nociceptive behavior by attenuating both TNFR1
      upregulation and Schwann cell activation in response to TNF injection. This
      prosaptide neurotrophin may also moderate nerve degeneration or promote
      regeneration. It is not known whether TX14(A) also acts rostral to the lesion
      site.

PMID- 9760129
TI  - Pituitary adenylate cyclase-activating peptide is upregulated in sensory neurons
      by inflammation.
AB  - The neuropeptide pituitary adenylate cyclase-activating peptide (PACAP) is
      expressed in sensory neurons. Expression of several neuropeptides is up-regulated
      in sensory neurons following inflammation. To examine whether also PACAP
      expression is regulated by inflammation, PACAP expression in L5 dorsal root
      ganglion (DRG) was determined, using in situ hybridization, after unilateral
      adjuvant-induced inflammation in the rat paw. At 12 h and day 3, but not day 21,
      the percentage of neurons expressing PACAP mRNA was greater in the innervating L5
      DRG. Similarly, PACAP mRNA expression in individual neurons was higher in the
      innervating L5 DRG at 12 h and day 3, but not day 21. Up-regulated PACAP
      expression following adjuvant injection suggests a role for PACAP in
      inflammation.

PMID- 9760130
TI  - Viability and survival of hNT neurons determine degree of functional recovery in
      grafted ischemic rats.
AB  - We recently reported behavioral improvements following intrastriatal
      transplantation of cryopreserved cultured human neuroteratocarcinoma-derived
      cells (hNT neurons) in rats with cerebral ischemia induced by occlusion of the
      middle cerebral artery. In the present study, the viability and survival of hNT
      neurons were evaluated immediately prior to the transplantation surgery and at 3
      months post-transplantation in ischemic rats. Cryopreserved hNT neurons were
      routinely thawed, and trypan blue exclusion viability counts revealed 52-95%
      viable hNT neurons before transplantation. Monthly behavioral tests, starting at
      1 month and extending to 3 months post-transplantation, revealed that ischemic
      animals that were intrastriatally transplanted with hNT neurons (approximately
      40000) and treated with an immunosuppressive drug displayed normalization of
      asymmetrical motor behavior compared with ischemic animals that received medium
      alone. Within-subject comparisons of cell viability and subsequent behavioral
      changes revealed that a high cell viability just prior to transplantation surgery
      correlated highly with a robust and sustained functional improvement in the
      transplant recipient. Furthermore, histological analysis of grafted brains
      revealed a positive correlation between number of surviving hNT neurons and
      degree of functional recovery. In concert with similar reports on fetal tissue
      transplantation, we conclude that high cell viability is an important criterion
      for successful transplantation of cryopreserved neurons derived from cell lines
      to enhance graft-induced functional effects.

PMID- 9760131
TI  - Immunolocalization of leukemia inhibitory factor in normal and denervated human
      muscle.
AB  - The cytokine leukemia inhibitory factor (LIF) stimulates myoblast proliferation
      in vitro and vivo and is neurotrophic for motor neurons. In experimentally
      reinnervated muscle, exogenous LIF application increases muscle mass through
      myofiber hypertrophy. The goal of this study was to evaluate possible sources of
      endogenous LIF in human muscle, and whether LIF immunoreactivity (-IR) was
      detectable in specific myofiber types and/or re-expressed in human denervated
      muscle. Our study shows that LIF-IR is constitutively detectable in type I
      myofibers of normal human muscle. In acute and chronically denervated and
      reinnervated human muscle, LIF-IR is found in all type I myofibers and in
      addition in some atrophic and almost all angulated atrophic type II myofibers.

PMID- 9760132
TI  - Medial nigral dopamine neurons have rich neurotrophin support in humans.
AB  - To assess the action of neurotrophin in human dopaminergic neurons, we studied
      the immunolocalization of neurotrophins or trks in human substantia nigra pars
      compacta (SNc). The neuromelanin-containing neurons in the SNc showed
      immunoreactivities for neurotrophins or trks, suggesting an autocrine/paracrine
      regulation. Quantitative analysis revealed that the percentage of those
      expressing NGF-like immunoreactivity (NGF-LI), BDNF-LI, NT3-LI, trkA-LI, trkB-LI,
      or trkC-LI was 66%, 74%, 85%, 66%, 71% or 86%, respectively. The percentage of
      cells expressing neurotrophins or trks was higher in the medial part than in the
      lateral part of the SNc. The preferential expression of neurotrophin-trk systems
      in the medial neurons may, at least partially, explain the differential
      susceptibility in Parkinson's disease.

PMID- 9760133
TI  - Sleep deprivation induces brain region-specific decreases in glutathione levels.
AB  - Rats were deprived of sleep for 96 h by the platform technique and total
      glutathione (GSHtau) levels were measured in seven different brain areas.
      Glutathione levels were found to be significantly reduced in the hypothalamus of
      sleep-deprived animals when compared with large platform (-18%) or home cage (
      31%) controls. Deprived rats also had reduced GSHtau levels in thalamus compared
      with home cage controls only. Glutathione levels did not differ among the three
      groups in any of the other brain areas examined. These results indicate that
      specific brain areas may be differentially susceptible to oxidative stress after
      sleep deprivation. The apparent vulnerability of the hypothalamus to these
      effects may contribute to some of the functional effects of sleep deprivation.

PMID- 9760135
TI  - Distribution of catechol-O-methyltransferase expression in human central nervous
      system.
AB  - Catechol-O-methyltransferase (COMT, EC 2.1.1.6) is a ubiquitous enzyme crucial to
      catechol metabolism. Two isoforms exist in the human central nervous system (CNS)
      and they are encoded by two transcripts (1.3 and 1.5 kb) in most human tissues.
      Using two alpha-32P-labeled probes, we found only the 1.5 kb transcript in all 16
      regions of the human CNS using commercially available Northern blots. Spinal cord
      had the highest and amygdala had the lowest levels of expression. The other CNS
      regions shared a similar level of expression. The distributions of COMT gene
      expression relative to whole brain between both probes were significantly
      correlated. Our study shows that the expression of the 1.5kb transcript is
      crucial for COMT activity in all regions of the human CNS.

PMID- 9760134
TI  - Adenosine A2A receptors modify motor function in MPTP-treated common marmosets.
AB  - Both adenosine A1 and A2 receptor populations are located in the striatum and can
      modify locomotor activity, and they may form a therapeutic target for Parkinson's
      disease (PD). Administration of the selective adenosine A2A antagonist (E)-1,3
      diethyl-8-(3,4-dimethoxystyryl)-7-methyl-3,7-dihydro-1H-pu rine-2,6-dione (KW
      6002) to MPTP-treated common marmosets increased locomotor activity. In contrast,
      administration of the selective A1 receptor antagonist 1,3-dipropyl-8
      cyclopentylxantine (DPCPX) had no effect on locomotion. Administration of the
      adenosine A2A receptor agonist 2-[p-[2-(2-aminoethylamino) carbonylethyl]
      phenethyl amino]-5'-N-ethylcarboxamidoadenosine (APEC) dose dependently
      suppressed basal locomotor activity. A minimally effective dose of APEC (0.62
      mg/kg, i.p) completely reversed the increase in locomotor activity produced by
      administration of KW-6002. The adenosine A2A receptor appears to be an important
      target for the treatment of basal ganglia disorders, particularly PD.

PMID- 9760136
TI  - Proprioception acts as the main source of input in human S-I activation
      experiments: a functional MRI study.
AB  - During tactile exploration cells in human somatosensory cortex S-I receive input
      from skin receptors and from proprioceptive feedback. To study the extent to
      which these sources contribute to cell activation we used functional magnetic
      resonance imaging (fMRI) in order to visualize the spatial extent and amplitude
      of activation in S-I during active finger movement and passive stimulation of
      finger tips. In all subjects (n = 6) we measured activation elicited by
      unilateral single finger tapping (active task) and mechanical stimulation of the
      palm of the index finger (passive task). In the finger tapping condition all
      subjects showed a strict contralateral activation of somatosensory cortex S-I and
      motor cortex M-I. In the passive stimulation experiment we found activation of
      the contralateral somatosensory cortex S-I only. Although subjects were trained
      to perform the finger movement with the same frequency and pressure in comparison
      to the passive stimulation, the activation within S-I induced by finger movements
      was always significantly larger than that induced by passive stimulation. This
      result implies that activation of somatosensory cortex originates to a large
      extent from proprioception while tactile input plays a minor role in S-I
      excitation.

PMID- 9760137
TI  - Stat3 and NFkappaB glial expression after excitotoxic damage to the postnatal
      brain.
AB  - The nuclear factor-kappa B (NFkappaB) and the signal transducer activator of
      transcription 3 (STAT3), are putative transcription factors activated by growth
      factors and cytokines, and involved in glial gene expression changes after
      neuronal injury. Immunocytochemical analysis of NFkappaB and STAT3 from 2 h to 14
      days after excitotoxic damage to the postnatal rat brain showed STAT3- and
      NFkappaB-positive glial cells at 2 h post-lesion, increasing in number to reach a
      maximum at day 1. Immunoreactivity then decreased but the glial scar remained
      positive. Glial STAT3 immunoreactivity was located in the nucleus up to 1 day
      post-lesion and in the nucleus, cytoplasm and cell processes from day 3. Glial
      NFkappaB immunoreactivity was mainly cytoplasmatic.

PMID- 9760138
TI  - Strong synergism between GABA(A) and glycine receptors on isolated carp third
      order neurons.
AB  - A strong synergistic interaction between the bicuculline-sensitive GABA receptor
      (GABA(A) receptor) and the strychnine-sensitive glycine receptor was observed in
      third-order neurons acutely isolated from crucian carp retina, with the use of
      the whole-cell patch-clamp recording technique. In 58 of 153 cells, 10 microM
      GABA or glycine separately applied to amacrine/ganglion cells failed to induce
      any responses or only induced small currents (<20 pA), while co-application of
      these two chemicals resulted in much larger responses (403.05+/-319.98 pA). The
      current induced by the co-application was mediated by chloride channels, and both
      GABA(A) and glycine receptors were involved in the potentiation. The underlying
      mechanisms of this interaction and its possible physiological role are discussed.

PMID- 9760139
TI  - 3-Nitropropionic acid-induced changes in the expression of metabolic and
      astrocyte mRNAs.
AB  - Systemic administration of 3-nitropropionic acid (3NPA) in rats produces
      bilateral striatal lesions which are similar to those seen in Huntington's
      disease (HD). We examined the effects of systemic 3NPA on the expression of
      cytochrome oxidase (COX-II and COX-IV), succinate dehydrogenase (SDH) and
      astrocytic glial fibrillary acidic protein (GFAP) mRNAs and on the activity of
      COX and SDH as assessed by the density of histochemical staining. COX-II and COX
      IV mRNA was reduced in rats with 3NPA-induced lesions, but not in those without,
      whereas SDH, but not COX, staining was significantly and dose-dependently reduced
      in both 3NPA treated groups. GFAP mRNA expression was increased in both intact
      striatum and cortex but was absent from the lesion core.

PMID- 9760140
TI  - Pre-exposure to alcohol does not sensitize to the rewarding effects of cocaine.
AB  - The conditioned place preference (CPP) induced by cocaine 2.5 mg/kg was measured
      in rats pre-exposed to ethanol (14 days with only 10% v/v ethanol followed by a
      free choice between ethanol solution and water for 14 days). Rats were divided
      according to their alcohol intake during the free choice period into low-drinking
      (<3 g/kg per day), intermediate-drinking and high-drinking (> 4 g/kg per day)
      rats. Cocaine-induced CPP was not modified in high-drinking rats relative to
      controls. Low-drinking rats had a lower CPP than high-drinking rats and controls.
      We conclude that pre-exposure to alcohol did not sensitize to the cocaine
      rewarding effects, and that alcohol low-drinking rats showed the lowest
      preference for cocaine.

PMID- 9760141
TI  - Immunocytochemical localization of GDNF in primary afferents of the lumbar dorsal
      horn.
AB  - Immunocytochemistry was used to identify glial cell line-derived neurotrophic
      factor (GDNF) in rat spinal cord. Strong GDNF labeling was found in fibers and
      terminals in laminae I and II (outer) and to a lesser extent in the remaining
      laminae. A few spinal ganglion cells also contained GDNF. After dorsal root
      transection GDNF disappeared from the dorsal horn and after dorsal root ligation
      there was accumulation of GDNF only on the ganglion side of the ligation. These
      findings demonstrate anterograde transport of GDNF within primary afferent
      fibers, which constitute the only source of GDNF labeling in the dorsal horn. The
      strong presence of GDNF in the superficial dorsal horn may indicate that GDNF has
      a role in pain transmission in the adult rat spinal cord.

PMID- 9760142
TI  - Transitory expression of NADPH diaphorase (NOS) in axonal swellings after spinal
      cord injury.
AB  - To investigate the sites of nitric oxide synthase (NOS) expression after a spinal
      cord (SC) injury, NADPH-d diaphorase histochemistry was performed in the SC of
      adult rats sacrificed at different times from 1 h to 90 days after both SC
      contusion or transection. NOS could first be seen 12 h after injury in axonal
      swellings (AS) (club shaped structures at the tip of damage axons, associated
      with tissue destruction). NOS expression reached a maximum 3 days after injury,
      and gradually disappeared after 7 days. Finally, AS collapsed leaving behind
      microcysts. NOS expression and the consequent production of nitric oxide could be
      involved in the pathophysiology of the secondary damage, and/or could reflect a
      failed attempt for axonal regeneration.

PMID- 9760143
TI  - Characteristics of muscular contraction caused by magnetic stimulation.
AB  - Characteristics of muscular contraction induced by magnetic stimulation were
      studied using isolated gastrocnemius muscles of a frog. The figure-eight coil
      position was regarded as 0 degrees when the direction of induced current was
      parallel to the muscle fiber axis, and 90 degrees when the induced current was
      perpendicular to the muscle fiber axis. Muscular contraction readily occurred
      with lower outputs of magnetic stimulation at 0 degrees and 180 degrees, but it
      was weak at 90 degrees and 270 degrees. Magnetic stimulation did not directly
      induce muscular contraction but it acted on the synapses forming end plates to
      muscle cells, and muscular contraction occurred if the direction of the eddy
      current was parallel to the nerve which innervated the muscle cells.

PMID- 9760144
TI  - Localization of a novel septin protein, hCDCrel-1, in neurons of human brain.
AB  - Synaptic function is critical for cell-cell communication and the
      characterization of proteins that function during vesicle formation, transport
      and fusion events will yield further insight into the mechanisms of synaptic
      transmission. We have cloned and characterized a gene product expressed in human
      brain called hCDCrel-1. This protein is a new member of the septin family of gene
      products that functions during cytokinesis in lower eukaryotes. In this study we
      characterize the expression of the hCDCrel-1 gene and localize the hCDCrel-1
      protein to neurons in adult human brain. hCDCrel-1 co-purifies with SNAP-25 and
      synaptophysin marked synaptosomes, suggesting a novel function for this gene
      family in the brain. Our data indicate that members of the septin family of
      proteins may function in synaptic vesicle transport, fusion or recycling events
      in the human brain.

PMID- 9760145
TI  - Planum temporale asymmetries in great apes as revealed by magnetic resonance
      imaging (MRI).
AB  - The planum temporale (PT), a portion of Wernicke's area, is important for
      linguistic functions in humans and is larger in the left compared to the right
      hemisphere. In this study, we assessed the presence and size of the PT in a
      sample of non-human primates including 21 great apes, four lesser apes, 11 Old
      World monkeys and eight New World monkeys using magnetic resonance imaging. The
      PT was measured in both the sagittal and coronal planes by use of multiplanar
      reformatting software. The PT could only be identified in the sample of great
      apes and not in the remaining non-human primate species. Within the great ape
      sample, the PT was larger in the left hemisphere than in the right in a
      statistical majority of the subjects. These results are consistent with the
      notion that the PT evolved as a definable structure about 15 million years ago
      and may have arisen as a result for selection for greater cortical folding which
      in turn led to greater gyrification in larger brains.

PMID- 9760146
TI  - Antisense strategies for the treatment of hematological malignancies and solid
      tumors.
AB  - If malignant growth is considered the result of abnormal gene expression, it is
      reasonable to use antisense nucleic acids for the treatment of malignant
      diseases. Antisense oligonucleotides can specifically down-regulate gene
      expression, and a number of first-generation antisense compounds have entered
      human clinical trials. In this review, some aspects relevant for the development
      of antisense-based drugs, such as the selection of appropriate target sequences,
      cellular delivery, and design of a clinical study, are described, using bcr-abl
      oncogene-directed antisense oligonucleotides as an example. In addition,
      potential target genes for antisense inhibition in hematology and oncology,
      including oncogenes and adhesion molecules, are summarized. Down-regulation of
      such adhesion molecules as members of the immunoglobulin superfamily and
      integrins may provide new modalities for mobilization of CD34+ hematopoietic stem
      cells into the peripheral blood. The review closes with an overview of ongoing
      clinical trials in the treatment of malignant diseases by antisense
      oligonucleotides.

PMID- 9760147
TI  - Iron status in 268 Danish women aged 18-30 years: influence of menstruation,
      contraceptive method, and iron supplementation.
AB  - The aim of the present study was to evaluate the influence of menstruation,
      method of contraception, and iron supplementation on iron status in young Danish
      women, and to assess whether iron deficiency could be predicted from the pattern
      of menstruation. Iron status was examined by measuring serum (S-) ferritin and
      hemoglobin (Hb) in 268 randomly selected, healthy, menstruating, nonpregnant
      Danish women aged 18-30 years. Iron deficiency (S-ferritin <16 microg/l) was
      observed in 9.7%, of the women, iron deficiency anemia (S-ferritin < 13 microg/l
      and Hb < 121 g/l) in 2.2%. Iron supplementation, predominantly as vitamin-mineral
      tablets containing 14-20 mg of ferrous iron was used by 35.1%. The median serum
      ferritin was similar in non-iron users and in iron users, whereas the prevalence
      of iron deficiency was 12.6% in nonusers vs. 4.3% in users, the prevalence of
      iron deficiency anemia 3.4% in nonusers vs. 0%, in users (p=0.17) In non-iron
      supplemented women, S-ferritin levels were inversely correlated with the duration
      of menstrual bleeding (rs= -0.25, p<0.001) and with the women's assessment of the
      intensity of menstrual bleeding (r(s)= -0.27, p<0.001), whereas no such
      correlations were found in iron-supplemented women. The results demonstrate that
      even moderate daily doses of ferrous iron can influence iron status in women with
      small iron stores. Women using hormonal contraceptives had menstrual bleeding of
      significantly shorter duration than those using intrauterine devices (IUD) or
      other methods. There was a high prevalence of small and absent body iron stores
      in young women, suggesting that preventive measures should be focused on those
      women whose menstruation lasts 5 days or longer, who have menstrual bleeding of
      strong intensity, who use an IUD without gestagen, and who are blood donors.

PMID- 9760148
TI  - Outcome of peripheral blood stem cell mobilization in advanced phases of CML is
      dependent on the type of chemotherapy applied.
AB  - High-dose chemotherapy with autologous transplantation of in vivo purged PBSC is
      a novel investigational approach to treating chronic myelogenous leukemia (CML)
      patients not responsive to conventional therapy with interferon-alpha (IFN-alpha)
      and not eligible for allogeneic transplantation. PBSC mobilization using either
      '5+2/7+3'-type chemotherapy or 'mini-ICE/ ICE' chemotherapy was investigated in
      43 patients with advanced phases of Philadelphia (Ph)-positive CML. Thirty
      patients were in late chronic phase (>12 months post diagnosis) and 13 patients
      in accelerated phase (AP) or blast crisis (BC). Contamination with Ph-positive
      cells was evaluated in harvests from 37/43 patients. The outcome of PBSC
      mobilization was dependent on the type of chemotherapy administered: a complete
      or major cytogenetic response (<35% Ph-positive metaphases) in leukapheresis
      collections was obtained in ten of 15 patients treated with 'mini-ICE/ICE' but in
      only three of 28 patients treated with '5 + 2/7 + 3' chemotherapy. One patient
      (1/43) in blast crisis died during mobilization therapy (2%). Twenty-five
      patients underwent PBSC transplantation and all of them engrafted successfully.
      Transplantation-related mortality was 0%. The data show that in advanced phases
      of CML the chance of harvesting Ph-negative peripheral blood stem cells depends
      on the type of chemotherapy used for mobilization.

PMID- 9760149
TI  - Time after bone marrow transplantation as an important variable for quality of
      life: results of a cross-sectional investigation using two different instruments
      for quality-of-life assessment.
AB  - Quality of life (QoL) was investigated in 56 BMT recipients. The objective was to
      compare QoL in terms of physical, emotional, and social functioning between
      patients within the first year after BMT (n = 15) and patients who were alive
      more than 1 year after BMT (n=41). The Functional Assessment of Cancer Therapy
      Scale (FACT-BMT) and the EORTC-Quality of Life Questionnaire (EORTC-QLQ C30) were
      used to evaluate QoL as perceived by the patients. Results show a significantly
      reduced general QoL in patients within the first year after BMT. Specific
      differences were identified on the dimensions of physical and emotional well
      being and the symptom scales of appetite loss, fatigue, pain, dyspnea, and nausea
      and vomiting. QoL improves significantly with time after BMT. We suggest that
      there should be more integration of QoL expectancy into the pre-BMT information
      process. Patients should be informed about potential deficits in physical and
      emotional well-being within the first year after BMT. This could enhance insight
      and compliance in the critical period early after BMT.

PMID- 9760150
TI  - Effects of thrombopoietin on megakaryocyte colony formation from leukemic cells
      at diagnosis and from marrow cells after induction chemotherapy for acute
      leukemias.
AB  - We have studied the effects of recombinant human thrombopoietin (TPO, mpl ligand)
      on the megakaryocyte colony formation from control human bone marrow cells, human
      leukemia cells at diagnosis, and human bone marrow cells after induction
      chemotherapy for acute leukemias. In the control human bone marrow cells from
      four adults and nine children who had localized malignancy and histologically
      normal-looking marrow. TPO alone effectively stimulated megakaryocyte colony
      formation, and interleukin-3 (IL-3) synergized this. In 17 patients (13 adults
      and four children) with acute myeloid leukemia (AML) at diagnosis, TPO stimulated
      leukemic colony formation in only one patient with FAB M7 subtype. In 11 children
      with acute lymphoblastic leukemia (ALL) at diagnosis, TPO did not enhance
      leukemic colony formation. After 17 courses of induction chemotherapy, nine for
      AML and eight for ALL, TPO stimulated megakaryocyte colony formation to a level
      of 51%, of that in the control human bone marrow cells. This may suggest that the
      administration of TPO to patients with M7 subtype warrants caution, whereas it is
      probably safe to give TPO at any time to patients with ALL. The administration of
      TPO to patients with acute leukemias after induction chemotherapy could stimulate
      megakaryocytopoiesis.

PMID- 9760151
TI  - Early detection of chronic disseminated Candida infection in leukemia patients
      with febrile neutropenia: value of computer-assisted serial ultrasound
      documentation.
AB  - Computer tomography (CT) is known to be as sensitive as magnetic resonance
      imaging (MRI) in detecting fungal microabscesses in chronic disseminated
      candidiasis. However, all imaging techniques have to be repeated in cases of
      suspected fungal infection. Therefore, use of the CT or MRI scan is limited. Only
      ultrasound (US) examinations can be repeated as often as needed. The disadvantage
      of US is a lack of sufficient documentation. We analyzed the value of computer
      assisted documentation in serial ultrasonography of leukemia patients with
      suspected chronic disseminated candidiasis. From November 1996 until October
      1997, a total of 220 ultrasound examinations (Kranzbuhler Logiq 500, 3.5 MHz
      convex array) were performed in 58 patients undergoing intensive chemotherapy.
      Initial US pictures were stored on a personal computer and compared with the live
      US at the time of reevaluation in cases of persistent fever. Ultrasound detected
      microabscesses in liver and/or spleen in eight of the 58 patients. Diagnosis was
      confirmed by autopsy/biopsy (n = 6), blood culture (n = 1), and a significant
      Candida antibody titer (n = 1). Focal lesions occurred only after neutrophil
      recovery. However, a newly evolving nonhomogeneous, micronodular pattern of liver
      and spleen occurred during febrile neutropenia in three patients, and two of
      these developed focal lesions subsequently. Follow-up was easy, since US pictures
      could be compared directly with stored examinations on screen. We conclude that
      serial US is sensitive in detecting microabscesses in the liver or the spleen.
      Computer-assisted US documentation proved to be a helpful tool for detection as
      well as in the follow-up of patients with chronic disseminated candidiasis.

PMID- 9760152
TI  - Type IV Ehlers-Danlos syndrome with platelet delta-storage pool disease.
AB  - A case of type IV Ehlers-Danlos syndrome with a partial platelet delta-storage
      pool disease is reported. The diagnosis of Ehlers-Danlos was clinical. The
      platelet-dense granule deficiency was determined by ultrastructural platelet
      morphology. Dense bodies were decreased in number, and most showed loss or
      fragmentation of electron-dense material. Aggregation studies revealed a retarded
      response to ristocetin and arachidonic acid, which was corrected with
      desmopressin acetate-DDAVP.

PMID- 9760153
TI  - Transient myeloproliferative disorder with 11q23 aberration in two neonates with
      Down syndrome.
AB  - Infants with Down syndrome may develop a transient myeloproliferative disorder
      (TMD) with the features of acute leukemia but resolving in a spontaneous
      remission. Chromosomal aberrations in addition to trisomy 21 have only rarely
      been described. In many cases of infant acute leukemia band q23 of chromosome 11
      is involved in nonrandom translocations, often resulting in a rearrangement of
      the ALL-1 (MLL, HRX, HTRX 1) gene. Generally, this translocation carries a bad
      prognosis. We describe two newborn girls with Down syndrome and TMD in whom the
      constitutional trisomy 21 was combined with an acquired abnormality of chromosome
      11. During the TMD the morphological and immunologic features were consistent
      with those of megakaryoblastic leukemia. The chromosome 11 abnormalities were
      del(ll)(q23), but rearrangements of the ALL-1 gene were not found. Our patients
      had remissions that occurred spontaneously or after a mild chemotherapy. The
      important finding is that additional chromosomal changes may occur during TMD in
      Down syndrome. The fact that the abnormality was in region 11q23 raises the
      question of whether the risk for developing leukemia is increased under these
      conditions.

PMID- 9760154
TI  - Molecular detection of a late-appearing BCR-ABL gene in a child with T-cell acute
      lymphoblastic leukemia.
AB  - Approximately 2-5% of children with newly diagnosed acute lymphoblastic leukemia
      (ALL) have a Philadelphia (Ph) chromosome detectable on cytogenetic analysis,
      which is associated with a poor prognosis. In rare ALL cases the Ph chromosome
      may appear in leukemic cells during the course of the disease. We report here the
      case of a 5.5-year-old male patient with T-ALL who was found to have the b2a2 BCR
      ABL mRNA transcript by reverse transcriptase-polymerase chain reaction (RT-PCR)
      at first marrow relapse. At the time of initial diagnosis, no BCR-ABL transcripts
      had been detected by PCR in the patient's blood and marrow samples. Further
      studies were performed using a competitive PCR titration assay and the
      fluorescence in situ hybridization (FISH) method to monitor the leukemic clone.
      Progression of the disease was associated with a higher BCR-ABL transcript level
      and an increasing proportion of BCR-ABL-positive cells. Metaphase FISH analysis
      identified the presence of the BCR-ABL fusion gene on a normal chromosome 22.
      This study shows that a late-appearing Ph translocation in ALL may be
      cytogenetically invisible. Quantitative RT-PCR and FISH techniques are
      appropriate and efficient methods for detecting these rare ALL variants
      expressing the BCR-ABL fusion gene and for estimating the level of residual
      disease following treatment.

PMID- 9760155
TI  - Sometimes it really is appendicitis: case of a CML patient with acute
      appendicitis.
AB  - We report on the case of a 24-year-old white man with a history of chronic
      leukemia treated with unrelated bone marrow transplantation and chemotherapy who
      was correctly diagnosed with appendicitis rather than typhlitis. The approach to
      diagnosing an acute abdomen in the leukemic patient is discussed, with particular
      focus on appendicitis vs. typhlitis. A focused CT scan proved to be instrumental
      in making the correct diagnosis of appendicitis in our patient. The literature on
      this topic for the past 30 years is reviewed. The purpose of our report is to
      demonstrate that despite the recent trend toward diagnosing RLQ pain as typhlitis
      which requires medical management, there are still instances where it 'really is'
      appendicitis. Appendicitis, therefore, must always be ruled out in the leukemic
      patient.

PMID- 9760156
TI  - Bulky lymphadenopathy in acute myeloid leukemia.
AB  - Two cases of acute myeloid leukemia (AML) presenting with bulky adenopathy are
      reported. Both patients were febrile at admission and showed massive and diffuse
      lymph node involvement, hepatomegaly, and splenomegaly. Erythematopapular
      leukemic skin lesions were present in one case at the onset and developed in the
      other at the time of relapse. Anemia, thrombocytopenia, and moderate leukocytosis
      were present in both. The presence of immature cells in peripheral blood and bone
      marrow allowed a rapid diagnosis of AML, FAB M1, in one patient. In the other
      case, owing to the paucity of immature cells in peripheral blood and bone marrow,
      lymph node biopsy with histology, imprint cytology, and immunocytochemistry were
      essential for the diagnosis (AML, FAB M2, with trilineage dysplasia and
      basophilic involvement). Both patients achieved complete remission (CR), followed
      by an early relapse 3 months later. They underwent allogeneic bone marrow
      transplantation (BMT) from HLA identical siblings. One patient is actually alive
      and in CR at 6 months after BMT; the other patient showed a leukemic regrowth
      after transplantation and died 4 months later.

PMID- 9760157
TI  - Acute myelogenous leukemia (FAB AML-M1) in the setting of HIV infection and G-CSF
      therapy: a case report and review of the literature.
AB  - Although hematologic dysplasia is common in HIV disease, evolution to AML is
      unusual. We report a case of AML in a patient with stage-C3 AIDS who had been
      previously treated with granulocyte colony-stimulating factor (G-CSF). This 41
      year-old black man presented with pancytopenia (Hg 8.6 g/dl, Hct 24.3%, platelets
      16,000/mm3, WBC 0.6 x 10(3)/mm3) and hemoptysis. His peripheral smear manifested
      19% blasts. His bone marrow biopsy was hypocellular (20%) with greater than 90%
      blasts, which were positive for myeloperoxidase and Sudan black B. The blasts
      were negative for nonspecific esterase. Immunophenotypic analysis by flow
      cytometry showed the majority of cells to be of myeloid lineage, expressing CD13,
      and CD45 at low intensity. In addition, there was aberrant expression of CD2 and
      no expression of CD14 or CD4. The diagnosis of AML-FAB-M1 was made. The patient
      refused chemotherapy. Of the rare cases of AML in HIV patients previously
      reported in the literature, the majority were of the monocytic or myelomonocytic
      subtype. This case is of special interest because of prior G-CSF therapy. In this
      setting, the relationship between HIV, G-CSF, and subsequent AML is
      controversial.

PMID- 9760158
TI  - Cardiac involvement in HIV-related non-Hodgkin's lymphoma: a case report and
      short review of the literature.
AB  - We report a case of secondary heart involvement in AIDS-related primary lymphoma
      of the liver. A worsening dyspnea led to the diagnosis of pericardial effusion,
      and transesophageal echocardiography revealed the presence of large endocardial
      ventricular masses. Clinical suspicion of a lymphomatous origin was confirmed at
      the autopsy, which showed an extranodal dissemination pattern (heart, liver,
      intestine, and lung). In AIDS patients, both primary and secondary lymphomatous
      heart involvement are increasing in incidence. Clinical symptoms and signs are
      vague. Since the hematogenous route is the most common pattern of involvement,
      even extrathoracic lymphomas can present heart dissemination. Thus, it should be
      suspected in lymphoma patients who present with even mild aspecific heart
      symptoms. Appropriate imaging procedures include transesophageal echocardiography
      and, if possible, ECG-gated MRI. A negative transthoracic echocardiograph does
      not exclude the presence of myocardial tumor. Chemotherapy is only occasionally
      beneficial, and the prognosis remains poor.

PMID- 9760159
TI  - Extramedullary granulopoiesis mimicking recurrent lymphoma after prolonged
      administration of human recombinant granulocyte colony-stimulating factor.
AB  - Human recombinant granulocyte colony-stimulating factor (G-CSF) has become a
      treatment of choice for neutropenia of diverse etiologies. We describe a 71-year
      old man who, while receiving G-CSF for graft failure after peripheral blood stem
      cell transplant, developed dramatic extramedullary granulopoiesis that mimicked
      recurrent lymphoma.

PMID- 9760160
TI  - Chlorambucil-induced pulmonary disease: a case report and review of the
      literature.
AB  - A 77-year-old man developed pneumonitis while on chlorambucil therapy for chronic
      lymphocytic leukemia, with a cumulative dose of 2700 mg. The condition improved
      promptly with the discontinuation of the drug and initiation of steroids. A case
      report and review of the literature are presented in this paper.

PMID- 9760162
TI  - Monofunctional platinum amine complexes destabilize DNA significantly.
AB  - Both cis-[Pt(NH3)2(4-Me-Py)Cl]+ and trans-[Pt(NH3)2(4-Me-Py)Cl]+ bind DNA
      covalently at the N7 site of guanine residues forming mono-dentate adducts.
      However, like cisplatin and transplatin, only the cis isomer has anti-cancer
      activity, whereas the trans-isomer does not. In order to understand the molecular
      basis of the different activities associated with cis-[Pt(NH3)2(4-Me-Py)Cl]+ and
      trans-[Pt(NH3)2(4-Me-Py)Cl]+, the interactions of these two platinum compounds
      with the DNA heptamer CCTG*TCC:GGACAGG duplex (G* is the platinated guanine) have
      been examined. The reaction rate of cis-[Pt(NH3)2(4-Me-Py)Cl]+ with the single
      stranded CCTGTCC is significantly faster than that of the trans isomer. The
      solution structure of the platinum-DNA adducts has been studied by two
      dimensional NMR spectroscopy. Both the cis-platinum adducts and the trans
      platinum adducts destabilize the DNA duplex significantly. The melting
      temperature (Tm) of the platinated heptamer duplex is estimated to be 10 degrees
      C lower than for the unplatinated duplex by NMR. At 2 degrees C, the base pairs
      located on the 5' side of the oligonucleotide, beyond the platinum lesion site,
      are disrupted. Over time, the platinum-DNA complex decomposes and the cis
      [Pt(NH3)2(4-Me-Py)] platinum complex is gradually detached from DNA. No
      interstrand crosslinking is observed. The biological implications of the
      structural studies are discussed.

PMID- 9760161
TI  - Rapid tumor lysis in a patient with B-cell chronic lymphocytic leukemia and
      lymphocytosis treated with an anti-CD20 monoclonal antibody (IDEC-C2B8,
      rituximab).
AB  - In this report we present a patient with B-cell chronic lymphocytic leukemia who
      developed an acute tumor lysis syndrome after administration of the human anti
      CD20 antibody IDEC-C2B8 (RITUXIMAB) in standard dose of 375 mg/m2. IDEC-C2B8 has
      been demonstrated to have only mild and tolerable side effects in patients with
      follicular lymphoma. In these trials patients with lymphocytosis >5000/microl
      were excluded. Physicians must be aware of this hitherto unreported phenomenon in
      patients with high CD20-positive blood counts.

PMID- 9760163
TI  - 800 MHz 1H NMR solution structure refinement of oxidized cytochrome c7 from
      Desulfuromonas acetoxidans.
AB  - The solution structure of Desulfuromonas acetoxidans cytochrome c7 has been
      refined by using 1H-NMR spectra recorded at 800 MHz and by using pseudocontact
      shifts in the final energy minimization procedure. The protein, composed of 68
      amino acids, contains three paramagnetic heme moieties, each with one unpaired
      electron. The largely distributed paramagnetism broadens the lines in several
      protein parts. The structure is now relatively well resolved all over the
      backbone by the use of 1315 meaningful NOEs and 90 pseudocontact shifts. The
      statistical analysis of the structure indicates its satisfactory quality. The
      protein-fold is quite similar to that of the analogous four-heme cytochromes c3
      for those parts which can be considered homologous. The solvent accessibility and
      the electrostatic potential surfaces surrounding the three hemes have been
      analyzed in terms of their reduction potentials. The resulting magnetic
      susceptibility anisotropy data obtained from pseudocontact shifts are analyzed in
      terms of structural data.

PMID- 9760164
TI  - Monitoring the conformational flexibility of cytochrome c at low ionic strength
      by 1H-NMR spectroscopy.
AB  - Horse heart cytochrome c at pH 7 and low ionic strength is present as two
      conformers, as evidenced by 1H-NMR spectroscopy. The two structures have been
      calculated using NOE and pseudocontact shift constraints. They have the same
      folding patterns and are essentially equal, within the rmsd of the families. The
      two average structures have rmsd values of 0.049 nm and 0.093 nm for the backbone
      and the heavy atoms, respectively. Such a difference has been analyzed through a
      detailed analysis of the NOEs. It appears that the species at low ionic strength
      differs from the species present at high ionic strength by the displacement of
      some external residues, such as Gln16, Ile81 and Glu90. Other changes are
      monitored by the chemical shifts but they cannot be quantified at the present
      level of resolution. Ionic-strength-dependent structural rearrangements may be
      relevant with respect to the problem of molecular recognition.

PMID- 9760165
TI  - Solution structure of the cellulose-binding domain of endoglucanase I from
      Trichoderma reesei and its interaction with cello-oligosaccharides.
AB  - The solution structure of a synthetic 38-residue cellulose-binding domain (CBD)
      of endoglucanase I from Trichoderma reesei (CBD(EGI)) was determined by two
      dimensional 1H-NMR spectroscopy. 100 structures were generated from a total of
      599 NOE derived distance restraints and 28 phi and 14 chi dihedral angle
      restraints. For the final set of 19 selected structures, the rms deviation about
      the mean structure was 0.83+/-0.26 A for all atoms and 0.50+/-0.22 A for the
      backbone atoms. The structure of CBD(EGI) was very similar to that of CBD of
      cellobiohydrolase I from T reesei (CBD(CBHI)). The backbone trace of CBD(EGI)
      followed closely the irregular triple-stranded antiparallel beta-sheet structure
      of CBD(CBHI). Moreover, apart from the different side chains of Trp7 (CBD(EGI))
      and Tyr5 (CBD(CBHI)), the cellulose-binding face of CBD(EGI) was similar to that
      of CBD(CBHI) within the precision of the structures. Finally, the interaction
      between CBD(EGI) and soluble sugars was investigated using cellopentaose and
      cellohexaose as substrates. Experiments showed that the interactions between
      CBD(EGI) and cellobiose units of sugars are specific, supporting the previously
      presented model for the CBD binding to crystalline cellulose.

PMID- 9760166
TI  - Structural characteristics of bullfrog (Rana catesbeiana) transthyretin and its
      cDNA--comparison of its pattern of expression during metamorphosis with that of
      lipocalin.
AB  - Transthyretin, an extracellular thyroid-hormone-binding protein (THBP) in higher
      vertebrates, is synthesized and secreted by the choroid plexus of all classes of
      vertebrates, except fish and amphibians, and synthesized in the liver of
      endothermic animals. Here, we report the nucleotide sequence of the cDNA for a
      THBP found in plasma of bullfrog (Rana catesbeiana) tadpoles before the climax of
      metamorphosis. The amino acid sequence clearly shows this protein to be an
      amphibian transthyretin. The three-dimensional structure of bullfrog
      transthyretin was derived using homology modeling. Compared with transthyretins
      from other vertebrate species, bullfrog transthyretin is highly conserved at the
      thyroid hormone-binding sites and other important structural regions of the
      subunits. Bullfrog transthyretin mRNA was found in tadpole liver, but not in
      tadpole choroid plexus. Thus, during evolution, synthesis of transthyretin in the
      liver of metamorphosing amphibians preceded that in the choroid plexus of
      reptiles, birds and mammals. It was previously observed that the protein most
      abundantly synthesized and secreted by the choroid plexus in adult amphibians is
      a lipocalin [Achen, M. G., Harms, P. J., Thomas, T., Richardson, S. J.,
      Wettenhall, R. E. H. & Schreiber, G. (1992) J. Biol. Chem. 267, 23170-23174], in
      contrast to transthyretin being the most abundantly synthesized and secreted
      protein in the choroid plexus of mammals, birds and reptiles. Lipocalin mRNA was
      found in large amounts in tadpole choroid plexus, but not livers.

PMID- 9760167
TI  - An isopeptide bond splitting enzyme from Hirudo medicinalis similar to gamma
      glutamyl transpeptidase.
AB  - A new enzyme from Hirudo medicinalis capable of splitting gamma-glutamyl-p
      nitroanilide and Glu--Lys-(N6-gamma-glutamyllysine) (isopeptidic bond between the
      epsilon-amino group of lysine and the gammacarboxylic group of glutamic acid)
      isopeptide bonds was purified. The protein was partially sequenced at the amino
      acid level, and the complete nucleotide and amino acid sequences were determined
      after cDNA cloning. The new enzyme has more than 60% similarity at the amino acid
      level to vertebrate gammaglutamyl transpeptidase (gamma-GT). According to the
      cDNA, the new protein has a molecular mass of 65 521 Da and a length of 600 amino
      acids.

PMID- 9760168
TI  - Interferon-gamma variants with deletions in the AB surface loop--flexibility is a
      critical point for receptor binding.
AB  - The receptor-binding AB loop of recombinant human interferon-gamma (IFN-gamma)
      has multiple contacts with the extracellular part of the IFN-gamma receptor a
      chain (IFN-gammaRalpha). We explored the possible length of truncated AB loops
      and their conformations by molecular modelling. Deletions of two amino acids at
      the tip of the loop were tolerated in the model without van der Waals collisions
      of the AB loop with helix F. Based on these modelling results, two deletion
      mutants were constructed by overlap-extension PCR mutagenesis: des-(A23, D24)-IFN
      gamma and des-(N25, G26)-IFN-gamma. Both mutations were tolerated by the folding
      pattern of recombinant human IFN-gamma, as proved by CD spectroscopy. The
      stability of both mutants against cosolvent-induced unfolding was equal to that
      of wild-type IFN-gamma. In contrast to the biophysical similarities of wild-type
      and mutant IFN-gamma proteins, the biological activities of both mutants dropped
      significantly. Antiviral activity and human leucocyte antigen (HLA)-DR induction
      of des-(N25, G26)-IFN-gamma was 10% that of wild-type activity. des-(A23, D24)
      IFN-gamma had only 1% remaining activity. Receptor-binding experiments confirmed
      that both deletions had a negative influence on the affinity of recombinant human
      IFN-gamma to its cellular receptor. We conclude from this combined molecular
      modelling and mutagenesis experiments, that the reduced flexibility of the
      truncated AB loop abrogates the possibility of the formation of a 3(10) helix in
      the receptor-bound state as observed in the X-ray structure of the IFN
      gammaRalpha-IFN-gamma complex.

PMID- 9760169
TI  - Probing the inhibitor-binding site of aldose reductase with site-directed
      mutagenesis.
AB  - Aldose reductase (AR) has been implicated in the etiology of the secondary
      complications of diabetes, and enzyme inhibitors have been proposed as
      therapeutic agents. While effectively preventing the development of diabetic
      complications in animals, results from clinical studies of AR inhibitors have
      been disappointing, possibly due to poor potency in man. To assist in the design
      of more potent and specific inhibitors, crystallographic studies have attempted
      to identify enzyme-inhibitor interactions. Resolution of crystal complexes has
      suggested that the inhibitors bind to the enzyme active site and are held in
      place through hydrogen bonding and van der Waals interactions formed within two
      hydrophobic pockets. To confirm and extend these findings we quantified inhibitor
      activity with single, site-directed, mutant, human AR enzymes in which the apolar
      active-site residues tryptophan 20, -79, -111 and phenylalanine 115 were replaced
      with alanine or tyrosine, decreasing the potential for van der Waals
      interactions. Consistent with molecular models, the inhibitory activity of
      Tolrestat, Sorbinil and Zopolrestat decreased 800-2000-fold when tested with the
      mutant enzyme in which Trp20 was replaced with alanine. Further, alanine
      substitution for Trp111 decreased Zopolrestat's activity 400-fold, while
      mutations to Trp79 and Phe115 had little effect on the activity of any of the
      inhibitors. The alanine mutation at Trp111 had no effect on Tolrestat's activity
      but decreased the activity of Sorbinil by about 1000-fold. These latter effects
      were unanticipated based on the number of non-bonded interactions between the
      inhibitors, Tolrestat and Sorbinil, and Trp20 and Trp111 that have been
      identified in the crystal structures. In spite of these unexpected findings, our
      results are consistent with the hypothesis that AR inhibitors occupy the enzyme
      active site and that hydrophobic interactions between the enzyme and inhibitor
      contribute to inhibitor binding stability.

PMID- 9760170
TI  - The crystal structure of anionic salmon trypsin in complex with bovine pancreatic
      trypsin inhibitor.
AB  - The complex formed between anionic salmon trypsin (ST) and bovine pancreatic
      trypsin inhibitor (BPTI) has been crystallised, and the X-ray structure has been
      solved using the molecular replacement method. The crystals are hexagonal and
      belong to space group P6(1)22 with lattice parameters of a = b = 83.12 A and c =
      222.15 A. Data have been collected to 2.1 A and the structure has been refined to
      a crystallographic R-factor of 20.6%. Catalysis by salmon trypsin is
      distinguished by a Km value 20-fold lower than that for mammalian trypsins, and a
      k(cat) twice as high. The present ST-BPTI complex serves as a model for the
      Michaelis-Menten complex, and has been compared with corresponding bovine and rat
      trypsin (RT) complexes. The binding of BPTI to salmon trypsin is characterised by
      stronger primary interactions in the active site, and a somewhat looser secondary
      binding.

PMID- 9760171
TI  - Hypothermia enhances the biological activity of lipopolysaccharide by altering
      its fluidity state.
AB  - Lipopolysaccharides (LPS, endotoxin) of gram-negative bacteria are among the main
      causes of sepsis and septic shock. In the present study, the influence of
      temperature on the biological activity of LPS was investigated. Lowering the
      temperature from 37 degrees C to 34.5 degrees C or to 30 degrees C significantly
      enhances in vitro tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta
      and IL-6 release induced by different LPS chemotypes and heat-inactivated
      Escherichia coli. This cytokine-increasing effect of lowering the temperature is
      highly mediated by serum proteins, particularly by LPS-binding protein (LBP) and
      low-density lipoproteins (LDL). In contrast, cytokine production induced by the
      superantigen toxic shock syndrome toxin-1 (TSST-1) from Gram-positive
      Staphyloccoccus aureus decreases by around 70% at 30 degrees C as compared with
      37 degrees C, corresponding to the expected effect of change in temperature and
      regardless of the presence of serum proteins. In order to explain the unexpected
      biological hypothermia effect with regard to LPS, the fluidity state of the lipid
      A portion of LPS as one important physico-chemical property possibly involved was
      investigated. The fluidity, determined by fluorescence polarization measurements,
      was found to decrease with decreasing temperature. These data suggest that a low
      fluid LPS chemotype is biologically more active than a more fluid one (and vice
      versa). Statistical analysis of the results shows a strong correlation between
      cytokine secretion and fluidity state of a given LPS chemotype (0.71 < r < 0.89,
      all P<0.01). As a clinical consequence, these data may be one possible
      explanation for the higher mortality rate of hypothermic Gram-negative sepsis.

PMID- 9760172
TI  - Induction of the heat-shock response by antiviral prostaglandins in human cells
      infected with human immunodeficiency virus type 1.
AB  - Cyclopentenone prostaglandins inhibit the replication of several DNA and RNA
      viruses, including retroviruses. The antiviral activity has been associated with
      the induction of a 70-kDa heat-shock protein (HSP70), via activation of the heat
      shock transcription factor (HSF) in infected cells. In the present study we
      investigated the effect of prostaglandin A1 (PGA1) on the regulation of HSP70
      gene expression as well as on viral RNA and protein synthesis in CEM-SS cells
      during acute infection with human immunodeficiency virus type 1 (HIV-1). We
      report that HIV-1 infection does not alter HSF activation by PGA1, whereas it
      causes an increase in intracellular HSP70 mRNA levels, as a result of enhanced
      HSP70 mRNA stability. We also show that, as reported in studies of different
      virus/host cell models, PGA1 inhibits HIV-1 replication by acting at multiple
      levels during HIV-1 infection. In addition to the previously reported block of
      HIV-1 mRNA transcription, PGA1 was also found to inhibit viral protein synthesis.
      These results, together with the fact that prostaglandins are used clinically in
      the treatment of several diseases, open new perspectives in the search for novel
      antiretroviral drugs.

PMID- 9760173
TI  - Antiproliferative effects of SR31747A in animal cell lines are mediated by
      inhibition of cholesterol biosynthesis at the sterol isomerase step.
AB  - SR31747A is a new sigma ligand exhibiting immunosuppressive properties and
      antiproliferative activity on lymphocyte cells. Only two subtypes of sigma
      receptor, namely the sigma1 receptor and emopamil-binding protein, have been
      characterised molecularly. Only the sigma1 receptor has been shown to bind (Z)N
      cyclohexyl-N-ethyl-3-(3-chloro4-cyclohexylphenyl)pro pen-2-ylamine hydrochloride
      (SR31747A) with high affinity. It was demonstrated that the SR31747A effect on
      the inhibition of T-cell proliferation was consistent with a sigma1 receptor
      mediated event. In this report, binding experiments and sterol isomerase assays,
      using recombinant yeast strains, indicate that the recently cloned emopamil
      binding protein is a new SR31747A-binding protein whose activity is inhibited by
      SR31747A. Sterol analyses reveal the accumulation of a delta8-cholesterol isomer
      at the expense of cholesterol in SR31747A-treated cells, suggesting that
      cholesterol biosynthesis is inhibited by SR31747A at the delta8-delta7 sterol
      isomerase step in animal cells. This observation is consistent with a sterol
      isomerase role of the emopamil-binding protein in the cholesterol biosynthetic
      pathway in animal cells. In contrast, there is no evidence for such a role of the
      sigma1 receptor, in spite of the structural similarity shared by this protein and
      yeast sterol isomerase. We have found that SR31747A also exerts anti
      proliferative effects at nanomolar concentrations on various established cell
      lines. The antiproliferative activity of SR31747A is reversed by cholesterol.
      Sterol-isomerase overproduction enhances resistance of CHO cells. This last
      observation strongly suggests that sterol isomerase is implicated in the
      antiproliferative effect of the drug in established cell lines.

PMID- 9760174
TI  - Subunits composition and allosteric control in Carcinus aestuarii hemocyanin.
AB  - Carcinus aestuarii hemocyanin (Hc) exists in two aggregation forms at pH 7.5 and
      20 mM Ca2+: 24S accounting for 90% of total hemocyanin and 16S accounting for
      10%. Removal of metal cations by EDTA at neutral pH causes the complete
      dissociation of 24S hemocyanin into two different 16S. At pH 9.2, 24S hemocyanin
      dissociates into a pH stable 16S and a 5S component. The 5S component consists of
      three monomeric fractions named CaeSS1 (10%), CaeSS2 (50%) and CaeSS3 (40%); the
      latter fraction consisting of two isoforms. The fractions CaeSS1, CaeSS2 and
      CaeSS3 have been studied as far as their reassociation properties to form
      hexamers are concerned. We investigated the oxygen-binding properties of the
      native form (24S), the mixture of the two 16S forms, the pH-stable 16S alone and
      of purified subunit fractions to define the role of each species on the
      expression of the allosteric behaviour of the 24S aggregate. The analysis of O2
      binding data reveals that 24S-Hc can be well described by the modified Monod
      Wyman and Changeaux-model (nested MWC-model), while the half-molecules (16S) bind
      oxygen according to the simple MWC-model. The two hexameric 16S within the
      dodecameric 24S hemocyanin can be regarded as nested allosteric units. They
      behave as being functionally coupled in the T-states (tT and rT). In the R-states
      (tR and rR) the two half-molecules seem to be functionally uncoupled since they
      have the same values of oxygen binding constants as deduced for isolated 16S
      hexamers.

PMID- 9760175
TI  - Expression of a bioactive, single-chain choriogonadotropin in Dictyostelium
      discoideum.
AB  - Human choriogonadotropin (hCG) is a highly complex glycoprotein consisting of two
      non-covalently associated subunits. We aimed for the expression of a single-chain
      hCG in the soil amoebae Dictyostelium discoideum, a host which, in principle,
      provides simple genetics in combination with complex protein synthesis. To limit
      anticipated problems in mRNA translation, the first 30 bases of the coding
      sequence were altered to conform to the Dictyostelium preferred codon usage. We
      show that, immunologically, active single-chain hCG is indeed produced by
      Dictyostelium. Furthermore, this single-chain hCG is able to bind to the human
      luteinizing hormone/CG receptor and elicit a biological response. Its receptor
      binding affinity is comparable to single-chain hCG produced by mammalian cells.
      We conclude that Dictyostelium is able to express bioactive highly complex
      heterologous glycoproteins.

PMID- 9760176
TI  - Characterization of an acetyl-11-keto-beta-boswellic acid and arachidonate
      binding regulatory site of 5-lipoxygenase using photoaffinity labeling.
AB  - AKBA (acetyl-11-keto-beta-boswellic acid), a natural pentacyclic triterpene, is
      an orally active leukotriene-synthesis inhibitor, which acts by a 5-lipoxygenase
      directed, non-redox, non-competitive mechanism. It is the only leukotriene
      synthesis inhibitor so far identified that inhibits 5-lipoxygenase activity as an
      allosteric regulator and not by a reducing or competitive mechanism. To
      characterize AKBA's effector site we prepared azido125I-KBA (4-azido-5-125iodo
      salicyloyl-beta-alanyl-11-keto-beta-bo swellic acid) as a photoaffinity analogue,
      which inhibited 5-lipoxygenase activity as efficiently as the lead compound and
      specifically labeled human 5-lipoxygenase protein. The labeling of 5-lipoxygenase
      by azido-125I-KBA strictly depended on the presence of calcium ([Ca2+]free > 500
      nM) and was abolished by heat denaturation or by prior incubation with a series
      of pentacyclic triterpenes (e.g., amyrin, beta-boswellic acid, AKBA and 18a
      glycyrrhetinic acid). In contrast, 18-beta-glycyrrhetinic acid and competitive 5
      lipoxygenase inhibitors (e.g., ZM-230,487 and L-739,010) did not affect labeling.
      Arachidonic acid, in enzyme-activity-inhibiting concentrations, reduced
      photoincorporation (IC50 about 10 microM), whereas a variety of other long-chain
      fatty acids and their derivatives (e.g., arachidinic acid, arachidonic acid
      methyl ester, lipoxins A4 and B4) had no effect. The inhibitory arachidonate
      action on labeling was not affected by blocking the substrate-binding site by
      micromolar amounts of the competitive inhibitor L-739,010. Therefore, we suggest
      that AKBA binds in presence of calcium to a site which is distinct from the
      substrate binding site of 5-lipoxygenase. The AKBA-binding site is likely to be
      identical with a regulatory, second arachidonate binding site of the enzyme.

PMID- 9760177
TI  - Dipeptidyl-peptidase IV-beta--further characterization and comparison to
      dipeptidyl-peptidase IV activity of CD26.
AB  - Dipeptidyl peptidase IV-beta (DPP IV-beta) is a novel protein which shows a
      peptidase activity similar to the T-cell-activation antigen CD26. To further
      characterize this DPP IV-beta and confirm its cell surface expression, we have
      developed a purification strategy using the CD26- cell line C8166. The
      purification process includes biotinylation of cell surface proteins before
      preparation of cell extracts and processing by gel-filtration, ion-exchange and
      lectin chromatographies. Consistent with the molecular mass of DPP IV-beta
      estimated by gel-filtration chromatography, the final purified fraction,
      manifesting a typical DPP IV activity, showed a major biotinylated 75-80-kDa band
      in SDS/PAGE, thus suggesting the monomeric nature of this enzyme. Kinetic
      parameters of DPP IV-beta and the sensitivity to a new family of irreversible DPP
      IV inhibitors, were studied in comparison to CD26. Both enzymes followed a
      Michaelis kinetics with different Km values for Gly-Pro-NH-Np (NH-Np, para
      nitroanilide) hydrolysis (0.28+/-0.05 mM and 0.12+/-0.02 mM). More significant
      differences were observed in the sensitivity to inhibitors, which exerted a much
      higher activity on CD26 than on DPP IV-beta. These differences permitted us to
      study DPP IV-beta expression in CD26-expressing cells, showing the expression of
      this new enzyme in all lymphoid cells tested, and a rapid enhancement in
      phytohemagglutinin-stimulated or protein-A-stimulated peripheral blood
      mononuclear cells. Our results indicate that, although DPP IV-beta and CD26 are
      coexpressed and manifest a typical DPP IV activity, there are distinct features
      in their catalytic activities that may confer to each enzyme a complementary role
      in peptide processing.

PMID- 9760178
TI  - Changing transcription start sites in H-type alpha(1,2)fucosyltransferase gene
      (FUT1) during differentiation of the human erythroid lineage.
AB  - Recent studies have suggested that at least three transcription-initiation sites
      were present in the human H-type alpha(1,2)fucosyltransferase gene (FUT1). In the
      present study, we have investigated these transcription start sites of FUT1 in
      undifferentiated leukemic cells (K562) that have erythroid characteristics, in
      erythroleukemia cells (HEL), and in bone marrow cells. K562 cells used
      exclusively exon 1 as the start site. While HEL cells used mainly exon 2 as the
      start site, the major start site for bone marrow cells was within exon 7. In
      addition, we investigated the transcription start site(s) in vascular endothelial
      cells (ECV304) as an example of mature cells and found that the start site was
      predominantly within exon 7. The promoter activities were found in the 5'
      flanking regions of these three start sites after transfection of constructs with
      luciferase reporter gene into K562 and HEL cells. These findings suggested that
      the transcription start sites of FUT1 changed during differentiation of the
      erythroid lineage and that the tissue-specific and stage-specific expressions of
      the FUT1 were regulated by three distinct promoters. We also found that the 5'
      flanking region of exon 2 (intron 1) consisted of repetitive sequences
      (chromosome 19-specific 37-bp minisatellite repeats, Alu sequence and long
      terminal repeat) and that the start site of exon 2 was within the long terminal
      repeat. Thus, these repetitive sequences may play a role in the expression of the
      FUT1.

PMID- 9760179
TI  - The effect of two actin depolymerizing factors (ADF/cofilins) on actin filament
      turnover: pH sensitivity of F-actin binding by human ADF, but not of Acanthamoeba
      actophorin.
AB  - Actin depolymerizing factor (ADF) from vertebrates and actophorin from
      Acanthamoeba castellanii are members of a protein family that bind monomeric and
      polymeric actin and have been shown by microscopy to sever filaments. Here, we
      compare the properties of recombinant human ADF and actophorin using rabbit
      muscle actin. ADF binds tenfold more strongly than actophorin to monomeric actin
      (G-actin)-ATP, and both bind co-operatively to F-actin. ADF decorates filaments
      below pH 7.3 and induces substantial depolymerization at higher pH values
      [Hawkins, M., Pope, B., Maciver, S. K. & Weeds, A. G. (1993) Human actin
      depolymerizing factor mediates a pH-sensitive destruction of actin filaments,
      Biochemistry 32, 9985-9993], but, at all pH values tested, actophorin binds to
      filaments in a similar manner to ADF at pH 6.5. Both proteins increase the
      depolymerization rate at the pointed ends of gelsolin-capped filaments, but the
      effect of ADF is more marked at pH 8.0. Both proteins accelerate the nucleating
      activity when mixed with filamentous actin (F-actin), but not with gelsolin
      capped filaments, and they rapidly decrease the lengths of filaments as evidenced
      by electron microscopy. Both of these effects are best explained by a weak
      severing activity. Our results are discussed in relation to earlier models and to
      the structural changes observed when ADF binds F-actin [McGough, A., Pope, B.,
      Chiu, W. & Weeds, A. (1997) Cofilin changes the twist of F-actin: implications
      for actin filament dynamics and cellular function, J. Cell Biol. 138, 771-781].
      We also discuss the relevance of these observations to their possible roles in
      facilitating actin turnover in cells, thereby regulating filament dynamics in
      cell motility.

PMID- 9760180
TI  - Mutual conversion of fatty-acid substrate specificity by a single amino-acid
      exchange at position 527 in P-450Cm2 and P-450Alk3A.
AB  - The two eukaryotic fatty-acid hydroxylases P-450Cm2 and P-450Alk3A, which
      represent CYP52A4 variants naturally occurring in the yeast Candida maltosa, were
      characterized with respect to their substrate specificity. Whereas P-450Cm2 was
      found to catalyse lauric acid omega-hydroxylation with greater efficiency, P
      450Alk3A had higher palmitic acid turnover numbers compared to P-450Cm2,
      resulting in ratios of lauric acid to palmitic acid turnover rates of nearly 11
      and 3 for P-450Cm2 and P-450Alk3A, respectively. As shown by means of chimeric
      enzymes and site-directed mutagenesis, the key residue determining these
      differences in substrate specificity was found to be a single amino acid at
      position 527. Interestingly, the mutual exchange of valine (P-450Cm2) and leucine
      (P-450Alk3A) led to a direct transposition of specificity, suggesting that amino
      acids at this site may determine the efficiency of fatty-acid hydroxylation
      relatively independently of other active-site residues. This was further
      supported by the finding that P-450Cm2 and P-450Alk3A with methionine at position
      527 displayed almost identical hydroxylation activities. Moreover, methionine to
      leucine substitutions at the corresponding alignment position in P-450Cm1
      (CYP52A3), P-450Alk2A (CYP52A5) and P-450Alk5A (CYP52A9) altered the fatty-acid
      specificity of these enzymes. In comparison to the structure of the bacterial P
      450BM3 (CYP102), we propose that the amino acid at position 527 may serve to
      close the substrate-binding pocket near to the haem in the fatty-acid-omega
      hydroxylating P-450 of the CYP52 family.

PMID- 9760182
TI  - Analysis of the ternary complex formation of human urokinase with the separated
      two domains of its receptor.
AB  - Human urokinase-type-plasminogen-activator receptor (uPAR) is a glycolipid
      anchored membrane glycoprotein comprising three structurally similar domains. We
      have succeeded in direct observation of the ternary complex formation of single
      chain urokinase (scuPA) or its N-terminal fragment (ATF) with the separated
      domain-1 (N-terminal domain) and domain-(2+3) (internal and C-terminal domain) of
      human uPAR, by means of gel-filtration HPLC analysis. This complex was found to
      consist of the three components in an equimolar ratio (thus referred to as the
      three-part complex). To determine the nature of the interaction between these
      components, cross-linking experiments involving various kinds of cross-linkers
      and competitive binding assay on ELISA were performed. These experiments have
      shown that each uPAR domain can bind directly to scuPA at low affinity, and that
      both these domains contribute to the high-affinity binding between scuPA and uPAR
      in a synergistic manner. It can be considered that the synergistic effect of
      domain-1 and domain-(2+3) on scuPA binding would result from a conformational
      change, and that this steric event might trigger the signal transduction reported
      for scuPA/uPAR binding.

PMID- 9760181
TI  - Solution structure of thanatin, a potent bactericidal and fungicidal insect
      peptide, determined from proton two-dimensional nuclear magnetic resonance data.
AB  - Thanatin is the first inducible insect peptide that has been found to have, at
      physiological concentrations, a broad range of activity against bacteria and
      fungi. Thanatin contains 21 amino acids including two cysteine residues that form
      a disulfide bridge. Two-dimensional (2D) 1H-NMR spectroscopy and molecular
      modelling have been used to determine its three-dimensional (3D) structure in
      water. Thanatin adopts a well-defined anti-parallel beta-sheet structure from
      residue 8 to the C-terminus, including the disulfide bridge. In spite of the
      presence of two proline residues, there is a large degree of structural
      variability in the N-terminal segment. The structure of thanatin is quite
      different from the known structures of other insect defence peptides, such as
      antibacterial defensin and antifungal drosomycin. It has more similarities with
      the structures of various peptides from different origins, such as brevinins,
      protegrins and tachyplesins, which have a two-stranded beta-sheet stabilized by
      one or two disulfide bridges. Combined with activity test experiments on several
      truncated isoforms of thanatin, carried out by Fehlbaum et al. [Fehlbaum, P.,
      Bulet, P., Chernysh, S., Briand, J. P., Roussel, J. P., Letellier, L., Hetru, C.
      & Hoffmann, J. (1996) Proc. Natl Acad. Sci. USA 93, 1221-1225], our structural
      study evidences the importance of the beta-sheet structure and also suggests that
      anti-Gram-negative activity involves a site formed by the Arg20 side-chain
      embedded in a hydrophobic cluster.

PMID- 9760183
TI  - Molecular analysis of Chs3p participation in chitin synthase III activity.
AB  - Chitin is a minor but essential component of the cell wall of Saccharomyces
      cerevisiae, with functions in septum formation in the vegetative life cycle and
      also in conjugation and spore cell-wall synthesis in the sexual cycle. Of the
      three chitin synthases present in yeast, chitin synthase III (CSIII) is
      responsible for the synthesis of most of the chitin found in the cell, including
      a chitin ring at early budding, chitin interspersed in the cell wall, and chitin
      laid down during the sexual cycle. We have tagged Chs3p, the putative catalytic
      subunit of CSIII, with the immunoreactive epitope of influenza virus
      hemagglutinin to follow expression of the protein. Little correlation was found
      between the levels of transcription and translation of Chs3p and in vivo
      function, supporting our previous conclusion that regulation of CSIII occurs at
      the posttranslational level. To identify possible regions of the protein involved
      in catalysis or regulation, mutations were generated in the QRRRW 'signature
      sequence' of chitin synthases. Arginine residue mutations in Chs3p, and in Chs1p
      and Chs2p, resulted in a loss of both function in vivo and enzymatic activity.
      Mutations in a serine residue adjacent to glutamine in Chs3p caused loss of
      function in vivo with a moderate decrease in CSIII activity, suggesting a
      regulatory role for the serine residue in chitin biosynthesis. Several
      truncations in the unique hydrophilic carboxy-terminal region of Chs3p identified
      a sequence of about 25 amino acids that is required for both function and in
      vitro activity. Since this region is not present in Chs1 or Chs2, it may be
      involved in the specific regulation of CSIII.

PMID- 9760184
TI  - Molecular and pharmacological characterization of recombinant rat/mice N-methyl-D
      aspartate receptor subtypes in the yeast Saccharomyces cerevisiae.
AB  - The genes encoding the ionotropic N-methyl-D-aspartate (NMDA) receptor subunits
      NR1a, NR2B and NR2D were cloned in the multi-copy yeast-Escherichia coli shuttle
      vectors pMBO1 and pMB02. The protease-deficient yeast Saccharomyces cerevisiae
      c13-ABYS-86 (leu-, ura-, his-) was transformed with the recombinant plasmids
      pMBNR1a (leu+), pMBNR1a/pMBNR2D (ura+), pMBNR1a/pMBNR2D/ pMBNR2B (his+) or
      pMBNR1a/pMBNR2A/pMBNR2B, respectively, and was used to express the different NMDA
      receptor subunit genes. Western-blotting analysis with the specific NMDA receptor
      antibodies showed a clear but differently strong expression of the recombinant
      receptor proteins which were found to be only partially glycosylated in the cell
      membranes of the recombinant yeast strains. By immunofluorescence microscopy
      using the specific subunit antibodies and fluorescence-labeled secondary
      antibodies, the distinctly expressed NR1a and NR2D subunits could be located in
      the plasma membrane of the transformed yeast cells. Pharmacological
      characterization of crude membrane preparations of the recombinant yeast cells
      expressing 1-3 NMDA receptor subunits showed saturable binding of the glycine
      antagonist [3H]MDL105,519 with different Kd values of 56.88+/-5.38 nM (NR1a),
      1365.11+/-76 nM (NR1a/NR2D), 22.97+/-3.37 nM for NR1a/NR2B/NR2D and 7.4+/-1.2 nM
      for NR1a/NR2A/NR2B. The bound capacities were 13.07+/-0.92 (NRla), 14.63+/-0.50
      (NR1a/NR2D), 12.85+/-1.68 (NR1a/NR2B/NR2D) and 8.3+/-0.7 (NR1a/NR2A/NR2B) pmol/mg
      membrane protein. The [3H]MDL105,519 binding was inhibited by the glycine
      antagonist 5,7-dichlorokynurenate (DCKA), ethyl-2-carboxy-4.6-dichloro-3
      indoleacetate (ECDI) and itself, but not by glycine, D-serine and 1-amino
      cyclopropanecarboxylic acid (ACPC). Each of these recombinant receptor proteins
      consisting both of NR1 and NR2 subunits also showed a specific binding site for
      the NMDA agonist glutamate when using L-[3H]glutamate as a radioligand. Analysis
      of saturation experiments revealed that this ligand binds to a specific site with
      Kd values of 536+/-43, 688+/-60, and 856+/-48 nM for NR1a/NR2B, NR1a/NR2D, and
      NR1a/NR2B/NR2D respectively.

PMID- 9760185
TI  - Conserved sequence elements in human main type-H1 histone gene promoters: their
      role in H1 gene expression.
AB  - In man, the H1 class of histones consists of seven different isoforms, termed
      H1.1-H1.5, H1t and H1o. Analysis of the promoters of the respective genes reveals
      that all seven H1 gene promoters share conserved sequence elements: a TATA box at
      around position -25 (relative to the transcription start site), a CCAAT motif at
      about position -50 (except in the H1 promoter), an H1-box (AAACACA) around
      position -110 (except in the H1.1 promoter), and the highly conserved motif
      TGTGT/CTA (TG-box or CH1UE) at around nucleotide position -450 (except in the
      H1.1 promoter). Analysis of the H1.3 gene promoter was carried out with reporter
      gene assays (using the luciferase gene as a reporter gene) including stepwise
      deletion and site-directed mutagenesis. In addition, electrophoretic mobility
      shift assays were carried out for the analysis of protein/DNA interactions at
      conserved promoter motifs. Mutation analysis indicates that the CH1UE motif is
      involved in mediating the S-phase-dependent expression of the H1.3 gene.
      Comparison of H1 promoters shows that the CCAAT-box is extended in each case by
      CA. Mutational analysis indicates that only the CCAATCA heptanucleotide, but not
      just the CCAAT sequence mediates the effect of this element in H1 gene promoters.

PMID- 9760186
TI  - Fusion of two subunits does not impair the function of a [NiFeSe]-hydrogenase in
      the archaeon Methanococcus voltae.
AB  - [NiFe]-hydrogenases generally carry the bimetallic Ni-Fe reaction center on their
      largest subunit. The [NiFeSe]-hydrogenase Vhu from Methanococcus voltae has an
      unusual subunit composition. Some of the amino acids participating in the
      formation of the reaction center are within a separate, very small subunit,
      called VhuU. It consists of only 25 amino acids and contains the selenocysteinyl
      residue, a ligand to the Ni atom. We have tested whether the special
      configuration of the Vhu-hydrogenase is of particular biochemical relevance. We
      have constructed a fusion subunit derived from the VhuA and VhuU subunits by
      generating a gene fusion which was inserted into the chromosome of M. voltae by
      gene replacement. The enzyme was purified and shown to be as active as the wild
      type enzyme. M. voltae carries the genetic information for four different [NiFe]
      hydrogenases. In addition to the Vhu-hydrogenase, a second selenium-containing
      enzyme, Fru, has been purified. Two selenium-free enzymes, Vhc and Frc, are
      homologues of Vhu and Fru, respectively. Their gene groups, vhc and frc are
      transcribed only upon selenium depletion. The selenium-containing subunit VhuU
      has been implicated in their negative regulation. However, cells containing the
      fusion hydrogenase still exhibited normal regulation of the vhc andfrc promoter
      activities as tested in reporter gene constructs. This indicates that the free
      VhuU polypeptide is not required for the negative regulation of the vhc or frc
      genes.

PMID- 9760187
TI  - Biochemical characterization and crystal structure of a recombinant hen avidin
      and its acidic mutant expressed in Escherichia coli.
AB  - The mature hen avidin encoded by a synthetic cDNA was expressed in Escherichia
      coli in an insoluble form. After resolubilization, renaturation and purification,
      a recovery of about 20 mg/l cell culture was obtained. ELISA assays indicated no
      apparent differences in biotin binding between the natural and recombinant
      avidins. In addition, an acidic avidin mutant, bearing the substitutions Lys3-
      >Glu, Lys9--> Glu, Arg26-->Asp and Arg124-->Leu of four exposed basic residues,
      was produced. The protein, expressed and renatured as wild-type avidin, showed
      unaltered biotin-binding activity. The acidic pI (approximately 5.5) and lack of
      aggregation of the mutant allowed easy electrophoretic analysis under non
      denaturing conditions of the protein alone and of its complexes with biotin,
      biotinylated transferrin or peroxidase. Analysis of the sera from sensitized
      subjects revealed that the avidin mutant has altered antigenicity. Both
      recombinant avidins were crystallized and the three-dimensional structures solved
      by molecular replacement and refined to 0.22 nm resolution. The three-dimensional
      structures of the two recombinant molecules, in the absence of biotin and of
      glycosylation, are fully comparable with those of the natural hen avidin
      previously reported.

PMID- 9760188
TI  - Two distinct forms of human mast cell chymase--differences in affinity for
      heparin and in distribution in skin, heart, and other tissues.
AB  - Chymase, a chymotrypsin-like protease secreted by human mast cells, is generally
      considered to be a single enzyme. However, by heparin-agarose chromatography of
      high-salt extracts of human skin, we have consistently resolved three peaks of
      chymotryptic activity, eluting at 0.4 M NaCl (peak A), 1.0-1.2 M NaCl (peak B)
      and 1.8-2.0 M NaCl (peak C), with peak B containing 75-90% of the recovered
      activity. Each peak retained its identity upon rechromatography. The three peaks
      of activity were similar in substrate specificity and inhibitor profile and
      distinctly different from other chymotryptic enzymes, including cathepsin G and
      the stratum corneum chymotryptic enzyme. Examination of different tissues
      revealed that peak C was virtually absent from synovial tissue, was present as a
      minor component in skin and heart, but constituted the predominant chymotryptic
      activity in lung. Peaks B and C from skin tissue were further purified by
      chromatography on Sephacryl S-200. Both had a molecular mass of 28-29 kDa,
      yielded the N-terminal sequence reported for chymase, and on western blots
      reacted with a panel of polyclonal, monoclonal and antipeptide antibodies against
      chymase. Chymase C required higher concentrations of NaCl to overcome the
      stimulatory effects of heparin than did chymase B, but had a similar pH profile.
      Thus, human chymase exists in at least two distinct but similar forms, and the
      differences in heparin binding and tissue distribution could have important
      consequences for enzyme function.

PMID- 9760189
TI  - Sulfated di-, tri- and tetraantennary N-glycans in human Tamm-Horsfall
      glycoprotein.
AB  - The primary structures of 32 sulfated di-, tri- and tetraantennary N-glycans of
      human Tamm-Horsfall glycoprotein (THP) have been determined. THP was isolated
      from the urine of one healthy male donor. The intact carbohydrate chains were
      released by PNGase-F and fractionated via FPLC on Resource Q, HPLC on LiChrosorb
      NH2, and high-pH anion-exchange chromatography on CarboPac PA-1.
      Characterizations were performed using 500-MHz and 600-MHz 1H-NMR spectroscopy,
      in combination with sialidase treatments. The type of characterized N-glycans
      ranged from monosulfated to trisulfated N-glycans, whereby the sulfate groups
      were present as 3-O-sulfated Gal (Gal3S) and 4-O-sulfated GalNAc (GalNAc4S). A
      compilation of the established structures is shown below. [structure in text]

PMID- 9760190
TI  - Structural and serological studies on a new acidic O-specific polysaccharide of
      Proteus vulgaris O32.
AB  - The following structure of the O-specific polysaccharide chain (O-antigen) of the
      Proteus vulgaris 032 lipopolysaccharide (LPS) was established by 1H-NMR and 13C
      NMR spectroscopy, including two-dimensional NOESY and H-detected 1H,13C
      heteronuclear multiple-quantum coherence (HMQC) experiments: -->2)-alpha-L-RhapI
      (1-->2)-alpha-L-RhapII-(1-->4)-beta-D-++ +GalpA(I)-(1-->3)-beta-D-GlcpNAc-(1-->4)
      alpha-D-GalpA(II)-(1-- >. In addition, an O-acetyl group was detected, which,
      most probably, is located at position 3 of a part of RhapI residues. Serological
      studies, using rabbit polyclonal anti-(P. vulgaris 032) serum, homologous and
      heterologous Proteus O-antigens and related artificial antigens, revealed the
      importance of an a-D-GalA-associated epitope in manifesting the immunospecificity
      of P. vulgaris 032 and substantiated serological relationships between the O
      antigen studied and those of some other Proteus strains.

PMID- 9760191
TI  - Beta-1,3-galactosyltransferase and alpha-1,2-fucosyltransferase involved in the
      biosynthesis of type-1-chain carbohydrate antigens in human colon adenocarcinoma
      cell lines.
AB  - We studied the beta-1,3-galactosyltransferase (GalT) and alpha-1,2
      fucosyltansferase (FT) involved in the biosynthesis of type-1-chain carbohydrate
      antigens in human colon adenocarcinoma cell lines. We detected a GalT activity
      able to use GlcNAc as acceptor and found that lacto-N-biose I (Galbeta1-3GlcNAc)
      is the only reaction product. Such beta1,3GalT is kinetically similar to a pig
      trachea enzyme involved in mucin synthesis. The specific activity is high in
      cells that react strongly with anti-Lewis a and anti-Lewis b antibodies, and
      undetectable in a cell line that lacks antibody reaction. Reverse-transcriptase
      mediated PCR analysis followed by DNA sequencing indicated that secretor-type
      alpha1,2FT is expressed in the cells, while the H type alpha1,2FT is not. The
      apparent Km values for donor and acceptor substrates determined for alpha1,2FT
      are similar to those of secretor-type alpha1,2FT and the specific activity
      measured correlates with Lewis b antigen expression on the cell surface.
      Moreover, some of the cell lines express Lewis y and H type 2 antigens,
      indicating that secretor type alpha1,2FT is responsible for their synthesis.
      Results suggest that biosynthesis of type-1-chain tumor-associated antigens in
      human colon carcinoma cells is operated by secretor-type alpha1,2FT, as reported
      in normal mucosa, and that beta1,3GalT activity may play a relevant role in its
      control.

PMID- 9760193
TI  - Localization of a gene for incomplete X-linked congenital stationary night
      blindness to the interval between DXS6849 and DXS8023 in Xp11.23.
AB  - Congenital stationary night blindness (CSNB) is a nonprogressive retinal disorder
      characterized by night blindness, nystagmus, myopia, a variable decrease in
      visual acuity, an abnormal electroretinographic response, and a disturbance in
      dark adaptation. Two forms of X-linked CSNB have been defined, complete CSNB in
      which rod function is extinguished, and incomplete CSNB in which rod function is
      reduced but not extinguished, as seen by electroretinography and dark
      adaptometry. In studying a large family of Mennonite ancestry, we have confirmed
      linkage between the locus (CSNB2) for incomplete CSNB and genetic markers in the
      Xp11 region. In particular, lod scores of 12.25 and 15.26 at zero recombination
      were observed between CSNB2 and the markers DXS573 and DXS255. Detailed analysis
      of critical recombinant chromosomes in this extended family have refined the
      minimal region for the CSNB2 locus to the interval between DXS6849 and DXS8023 in
      Xp11.23.

PMID- 9760192
TI  - The SOX10/Sox10 gene from human and mouse: sequence, expression, and
      transactivation by the encoded HMG domain transcription factor.
AB  - The SOX genes form a gene family related by homology to the high-mobility group
      (HMG) box region of the testis-determining gene SRY. We have cloned and sequenced
      the SOX10 and Sox10 genes from human and mouse, respectively. Both genes encode
      proteins of 466 amino acids with 98% sequence identity. Significant expression of
      the 2.9-kb human SOX10 mRNA is observed in fetal brain and in adult brain, heart,
      small intestine and colon. Strong expression of Sox10 occurs throughout the
      peripheral nervous system during mouse embryonic development. SOX10 shows an
      overall amino acid sequence identity of 59% to SOX9. Like SOX9, SOX10 has a
      potent transcription activation domain at its C-terminus and is therefore likely
      to function as a transcription factor. Whereas SOX9 maps to 17q, a SOX10 cosmid
      has previously been mapped by us to the region 22q13.1. Mutations in SOX10 have
      recently been identified as one cause of Waardenburg-Hirschsprung disease in
      humans, while a Sox10 mutation underlies the mouse mutant Dom, a murine
      Hirschsprung model.

PMID- 9760194
TI  - Characterization of the human synaptogyrin gene family.
AB  - Genomic sequencing was combined with searches of databases for identification of
      active genes on human chromosome 22. A cosmid from 22q13, located in the
      telomeric vicinity of the PDGFB (platelet-derived growth factor B-chain) gene,
      was fully sequenced. Using an expressed sequence tag-based approach we
      characterized human (SYNGR1) and mouse (Syngr1) orthologs of the previously
      cloned rat synaptogyrin gene (RATSYNGR1). The human SYNGR1 gene reveals three
      (SYNGR1a, SYNGR1b, SYNGR1c) alternative transcript forms of 4.5, 1.3 and 0.9 kb,
      respectively. The transcription of SYNGR1 starts from two different promoters,
      and leads to predicted proteins with different N- and C-terminal ends. The most
      abundant SYNGR1 a transcript, the 4.5-kb form, which corresponds to RATSYNGR1, is
      highly expressed in neurons of the central nervous system and at much lower
      levels in other tissues, as determined by in situ hybridization histochemistry.
      The levels of SYNGR1b and SYNGR1c transcripts are low and limited to heart,
      skeletal muscle, ovary and fetal liver. We also characterized two additional
      members of this novel synaptogyrin gene family in human (SYNGR2 and SYNGR3), and
      one in mouse (Syngr2). The human SYNGR2 gene transcript of 1.6 kb is expressed at
      high levels in all tissues, except brain. The 2.2-kb SYNGR3 transcript was
      detected in brain and placenta only. The human SYNGR2 and SYNGR3 genes were
      mapped by fluorescence in situ hybridization to 17qtel and 16ptel, respectively.
      The human SYNGR2 gene has a processed pseudogene localized in 15q11. All
      predicted synaptogyrin proteins contain four strongly conserved transmembrane
      domains, which is consistent with the M-shaped topology. The C-terminal
      polypeptide ends are variable in length, display a low degree of sequence
      similarity between family members, and are therefore likely to convey the
      functional specificity of each protein.

PMID- 9760195
TI  - Japanese juvenile retinoschisis is caused by mutations of the XLRS1 gene.
AB  - We investigated the XLRS1 gene in Japanese patients with retinoschisis (RS). All
      exons of the XLRS1 gene were sequenced in 14 males, including a pair of
      monozygotic twins, from 11 individual families with RS and five of their mothers
      who are asymptomatic but diagnosed as carriers. Six kinds of missense mutations
      and a nonsense mutation, including six novel mutations, were detected in all 14
      patients and carriers. Mutations in the XLRS1 gene are also responsible for RS in
      non-Caucasian patients. Most Japanese RS cases are caused by an XLRS1 gene
      defect. A novel mutation, Glu72Lys, was found in four families, suggesting a
      common mutation in the Japanese population. Clinical features of RS patients with
      both the Glu72Lys and Pro193Leu mutations indicate that a genotype-phenotype
      correlation is not recognized in RS.

PMID- 9760196
TI  - Phenotypic variation in a family with mutations in two Hirschsprung-related genes
      (RET and endothelin receptor B).
AB  - Hirschsprung disease is a congenital malformation affecting 1 in 5000 live
      births. The absence of parasympathetic neuronal ganglia (Meissner, Auerbach) in
      the hindgut results in poor coordination of peristaltic movement, and a varying
      degree of constipation. Four different genes have been implicated in the
      pathogenesis of Hirschsprung disease: the RET tyrosine kinase receptor gene; one
      of its ligands, the glial cell line-derived neurotrophic factor (GDNF) gene; the
      endothelin receptor B (EDNRB) gene; and its ligand, endothelin-3 (EDN3).
      Recently, combinations of mutations in two of these genes (RET and GDNF) have
      been reported in Hirschsprung patients. We report a family with missense
      mutations in both the RET gene (R982C) and the EDNRB gene (G57S). In this family,
      three out of five members have the two mutations, but only one, a boy, has the
      Hirschsprung disease phenotype. This illustrates the complexity of the molecular
      background of Hirschsprung disease.

PMID- 9760197
TI  - Missense mutation and hexanucleotide duplication in the PAX2 gene in two
      unrelated families with renal-coloboma syndrome (MIM 120330).
AB  - We present a family with autosomal-dominant inheritance of renal insufficiency
      caused by renal hypoplasia in six individuals. In all affected individuals, signs
      of optic disk dysplasia were detected, but most patients were asymptomatic. A
      heterozygous missense mutation in the PAX2 gene causing a Gly75 to Ser
      substitution was present in all affected individuals. A second, unrelated patient
      presented with ocular complaints related to optic disk dysplasia, and had a
      history of vesico-ureteral reflux. A heterozygous hexanucleotide duplication in
      the PAX2 gene was detected leading to the duplication of GluThr at positions 74
      and 75. The mutations in these two families are the first mutations in the PAX2
      gene that do not lead to a truncated protein. Mechanistically, these mutations
      are expected to result in abnormal folding of the PAX2 protein. These
      observations further expand the spectrum of clinical features associated with
      PAX2 mutations, and suggest that a distinct genetic disorder can be identified in
      patients with renal dysplasia through a careful eye examination. As the ocular
      manifestations in this syndrome are variable anomalies of retinal and optic disk
      dysplasia, we prefer the term "papillo-renal syndrome".

PMID- 9760198
TI  - A high proportion of mutations in the BRCA1 gene in German breast/ovarian cancer
      families with clustering of mutations in the 3' third of the gene.
AB  - We have analyzed 61 German breast and breast/ovarian cancer families for BRCA1
      mutations using single-strand conformation polymorphism analysis (SSCP) followed
      by sequencing. Forty-seven of the families had at least three cases (at least two
      under 60 years) and 14 families had only two cases of breast/ovarian cancer (at
      least one under 50 years). Twenty-eight families were breast/ovarian and 33 were
      breast cancer-only families. Eighteen mutations in BRCA1 were detected in 11/28
      breast/ovarian cancer families and 7/33 breast cancer families and none in the
      families with only two cases. We identified 17 truncation mutations (8
      frameshift, 7 nonsense and 2 splice variants) and one missense mutation. Seven of
      these are novel and two, the 5382insC and 5622C-->T mutations, occurred in two
      apparently unrelated families. The genotype of the two families with the 5382insC
      mutation is compatible with the rare haplotype segregating with the 5382insC
      mutation in different populations, further supporting its European origin. One
      unclassified missense alteration, R841W, was found in one family but did not
      segregate with the disease, suggesting that it is more likely a polymorphism. We
      also report and discuss the sequence of several new unclassified single
      nucleotide changes first identified by SSCP. Of the 18 mutations, 13 occurred in
      the 3' third of the gene (end of exon 11-24) and ovarian cancers were found in
      eight of these families.

PMID- 9760199
TI  - Mutations in the pterin-4alpha-carbinolamine dehydratase (PCBD) gene cause a
      benign form of hyperphenylalaninemia.
AB  - Four patients with primapterinuria, postulated to be due to pterin-4alpha
      carbinolamine dehydratase (PCD) deficiency, were diagnosed by biochemical and DNA
      analysis. All four patients presented in the neonatal period with
      hyperphenylalaninemia, and elevated neopterin and decreased biopterin levels in
      the urine. These symptoms are common to 6-pyruvoyltetrahydropterin synthase
      deficiency and thus there is a danger of misdiagnosis. In addition, all four
      patients had elevated urinary excretion of primapterin (7-biopterin), the only
      persistent biochemical abnormality. Analysis of fibroblast DNA from the patients
      identified the following mutations in the PCBD gene: one patient homozygous for
      the missense mutation E96K and one homozygous for the nonsense mutation Q97X,
      both in exon 4; one compound heterozygote with the mutations E96K and Q97X; and
      one patient with two different homozygous mutations: E26X in exon 2 and R87Q in
      exon 4. In two families, the parents were investigated and found to be obligate
      heterozygotes for particular mutations. One sibling was found to be unaffected.
      These results further substantiate the idea that primapterinuria is associated
      with mutations in the PCBD gene.

PMID- 9760200
TI  - Nine novel germline mutations of STK11 in ten families with Peutz-Jeghers
      syndrome.
AB  - Peutz-Jeghers Syndrome (PJS) is an autosomal dominant hereditary disease
      characterized by hamartomatous polyposis involving the entire bowel. Recently
      STK11, a gene bearing a mutation responsible for PJS, was isolated. We
      investigated the entire coding region of STK11 in 15 unrelated PJS families by
      the PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism)
      method and PCR-direct sequence analysis, and found nine different, novel
      mutations among ten of those families. One nonsense mutation and five different
      frameshift mutations (two families carried the same mutation), all of which would
      cause truncation of the gene product, were found in seven families; mutations
      found in five families were clustered within exon 6. Among these five mutations,
      three occurred at the mononucleotide-repeat region (CCCCCC) of codons 279-281,
      suggesting that this region is likely to be a mutational hotspot of this gene.
      One of the remaining three families carried a 3-bp in-frame deletion that would
      eliminate an asparagine residue within a kinase domain of the product; the other
      two carried intronic mutations at or adjacent to the consensus dinucleotide
      sequences of splice-acceptor or -donor sites, which were likely to lead to
      aberrant splicing.

PMID- 9760201
TI  - Molecular characterization and delineation of subtle deletions in de novo
      "balanced" chromosomal rearrangements.
AB  - To test the hypothesis that the phenotypic abnormalities seen in cases with
      apparently balanced chromosomal rearrangements are the result of the presence of
      cryptic deletions or duplications of chromosomal material near the breakpoints,
      we analyzed three cases with apparently balanced chromosomal rearrangements and
      phenotypic abnormalities. We characterized the breakpoints in these cases by
      using microsatellite analysis by polymerase chain reaction and fluorescence in
      situ hybridization analysis of yeast artificial chromosome clones selected from
      the breakpoint regions. Molecular characterization of the translocation
      breakpoint in patient 1 [46,XY,t(2;6)(p22.2;q23.1)] showed the presence of a 4-
      to 6-Mb cryptic deletion between markers D6S412 and D6S1705 near the 6q23.1
      breakpoint. Molecular characterization of the proximal inversion 7q22.1
      breakpoint in patient 2 [46,XY,inv(7)(q22.1q32.1)] revealed the presence of a 4
      Mb cryptic deletion between D7S651 and D7S515 markers. No deletion or duplication
      of chromosomal material was found near the breakpoints in patient 3
      [46,XX,t(2;6)(q33.1;p12.2)]. Our study suggests that a systematic molecular study
      of breakpoints should be carried out in cases with apparently balanced
      chromosomal rearrangements and phenotypic abnormalities, because cryptic
      deletions near the breakpoints may explain the phenotypic abnormalities in these
      cases.

PMID- 9760202
TI  - A novel splice site mutation in the tissue inhibitor of the metalloproteinases-3
      gene in Sorsby's fundus dystrophy with unusual clinical features.
AB  - Sorsby's fundus dystrophy (SFD) is an autosomal dominant macular dystrophy which
      is developed usually in the third or fourth decade of life, and is characterized
      by central visual loss and nyctalopia due to fundus changes of exudative or
      atrophic macular lesions. Its functional prognosis is usually poor because of
      disciform macular scars and peripheral chorioretinal atrophies. To date, five
      different mutations in the tissue inhibitor of the metalloproteinases-3 (TIMP3)
      gene have been identified in families of a wide geographic origin, all of which
      are missense mutations that cause replacement by cysteine of conserved amino
      acids in the C-terminus of exon 5 of TIMP3. We have studied two Japanese families
      with SFD, the first report from the Eastern world, and identified a novel 3'
      splice site mutation in the TIMP3 gene, namely a single base insertion at the
      intron 4/exon 5 junction which converts the consensus sequence CAG to CAAG in the
      splice acceptor site. In addition, our patients displayed a distinctive clinical
      expression in that they developed macular dystrophies at an approximately 30-year
      later age of onset and preserved functional vision until later life with
      essentially uninvolved peripheral retina. The present findings may provide some
      insight into the genotype-phenotype relationship in SFD.

PMID- 9760203
TI  - Genetics strongly determines the wall thickness of the left and right carotid
      arteries.
AB  - In 76 supposedly healthy families, we investigated the familial resemblance of
      left and right carotid intima-media thickness (IMT) measured by B-mode
      ultrasonography and the impact of the common apolipoprotein E (apo E)
      polymorphism and the insertion/deletion polymorphism of the angiotensin
      converting enzyme (ACE). Genetic factors accounted for about 30% of IMT
      variation. The insertion/deletion ACE polymorphism did not influence carotid IMT,
      whereas apoE polymorphism explained about 1.5% of only right carotid IMT
      variability independently of cholesterol levels. The apo epsilon2 and apo
      epsilon4 alleles were associated with lower right carotid IMT than was the apo
      epsilon3 allele. We conclude that genetic factors strongly contribute to IMT
      variability in healthy people and that the apo E polymorphism may be one of these
      factors.

PMID- 9760205
TI  - The Usher syndrome in the Lebanese population and further refinement of the USH2A
      candidate region.
AB  - Usher syndrome (USH) is an autosomal-recessive disease characterized by
      neurosensory deafness and progressive retinitis pigmentosa. So far, three
      clinical types of Usher syndrome have been defined, and are caused by defects at
      more than eight loci. We report the linkage analysis of seven Lebanese families
      with Usher syndrome, two with type I (USH1) and five with type II (USH2). We
      demonstrate that one family is linked to the USH1C locus, a rare form of USH1
      only reported in the French Acadian population. Linkage analysis of the five USH2
      families with recently mapped loci allowed us to reduce the USH2A candidate
      region to a very small interval flanked by D1S2646/D1S2629 and D1S2827.
      Furthermore, haplotype comparison between the different families suggests a
      founder effect for the USH2A mutation among the different Lebanese ethnic groups,
      while a genetic heterogeneity is noted for Usher syndrome type I.

PMID- 9760206
TI  - Linkage disequilibrium and linkage analysis of the glucose-6-phosphatase gene.
AB  - Recent studies have indicated that the four most common mutations account for 78%
      of mutant alleles in the glucose-6-phosphatase (G6Pase) gene. A significant
      fraction of mutant alleles remain unidentified. Thus, informative polymorphic
      markers are necessary for linkage analysis in carrier testing and prenatal
      diagnosis in families where mutations can not be identified. The common mutations
      appear to be ethnic-specific, suggesting that the individual mutations may have a
      common founder. With the recent discovery of the nucleotide 1176 polymorphism, we
      have studied whether these mutations are in linkage disequilibrium with the
      polymorphism. The results of polymerase chain reaction/allele-specific
      oligonucleotide analysis show that nucleotide 1 176 C is in linkage
      disequilibrium with mutations R83 C and R83H, and with the splicing mutation 727G
      ->T. The 1176T polymorphism is in linkage disequilibrium with 459insTA. A GT
      repeat polymorphism has also been found. However, its heterozygosity is low. The
      1176 nucleotide polymorphic marker can be used in carrier and prenatal diagnosis
      of GSD1a families that have unidentified mutations and are informative for this
      marker.

PMID- 9760204
TI  - Molecular cloning of the chromosomal breakpoint in the LIS1 gene of a patient
      with isolated lissencephaly and balanced t(8;17).
AB  - Karyotypic analysis of a patient exhibiting a phenotype of isolated
      lissencephaly, and of her parents, revealed a de novo balanced translocation,
      t(8;17)(p11.2; p13.3). Since the lissencephaly (LIS1) gene was known to be
      located on 17p13.3, we investigated whether the translocation might involve this
      gene. We performed Southern analysis using cosmid clones that contained genomic
      sequences corresponding to LIS1, and found that the breakpoint was located within
      intron 1. As sequence analysis of the parental chromosomes in the vicinity of the
      breakpoint identified no additional putative transcripts, haploinsufficiency of
      the LIS1 gene is likely to be solely responsible for the patient's lissencephaly.
      Characterization of both breakpoints indicated a possible involvement of
      repetitive sequences in the recombigenic process that led to the translocation.

PMID- 9760207
TI  - Extensive polymorphism of the FUT2 gene in an African (Xhosa) population of South
      Africa.
AB  - The human secretor type alpha(1,2)fucosyltransferase gene (FUT2) polymorphism was
      investigated in Xhosa and Caucasian populations of South Africa by polymerase
      chain reaction-restriction fragment length polymorphism and DNA sequencing. Six
      new base substitutions were found in the coding region of FUT2. A single base (C)
      deletion at nucleotide 778, which led to a frame shift and produced a stop codon
      at codon 275, was responsible for the enzyme inactivation. Three nonsynonymous
      base substitutions, A40G (lle14Val), C379T (Arg127Cys), and G481A (Asp161Asn),
      and two synonymous base substitutions, A375G (Glu125) and C480T (His160), were
      also identified in functional alleles. As a result, seven new alleles, Se40,
      Se481, Se40,481, Se357,480, Se357,379,480, Se375, and se357,480,778 were
      identified. Population studies revealed that an allele containing a nonsense
      mutation G428A (Trp143stop) (se428) was the common null allele in both Xhosa and
      Caucasian populations, whereas an allele containing a missense A385T (Ile129Phe)
      mutation (se357,385), which is the common null allele in Orientals, was found to
      be absent from both populations. The heterozygosity rates of FUT2 genotypes were
      as high as 0.75 in the Xhosa population and 0.65 in the Caucasian population.
      Therefore, the extensive polymorphism and race specificity of the FUT2 gene make
      it suitable for application as a new tool in genetic studies of modern human
      evolutionary history.

PMID- 9760208
TI  - A global survey of haplotype frequencies and linkage disequilibrium at the DRD2
      locus.
AB  - A four-site haplotype system at the dopamine D2 receptor locus (DRD2) has been
      studied in a global sample of 28 distinct populations. The haplotype system spans
      about 25 kb, encompassing the coding region of the gene. The four individual
      markers include three TaqI restriction site polymorphisms (RSPs) -- TaqI "A",
      "B", and "D" sites -- and one dinucleotide short tandem repeat polymorphism
      (STRP). All four of the marker systems are polymorphic in all regions of the
      world and in most individual populations. The haplotype system shows the highest
      average heterozygosity in Africa, a slightly lower average heterozygosity in
      Europe, and the lowest average heterozygosities in East Asia and the Americas.
      Across all populations, 20 of the 48 possible haplotypes reached a frequency of
      at least 5% in at least one population sample. However, no single population had
      more than six haplotypes reaching that frequency. In general, African populations
      had more haplotypes present in each population and more haplotypes occurring at a
      frequency of at least 5% in that population. Permutation tests for significance
      of overall disequilibrium (all sites considered simultaneously) were highly
      significant (P<0.001) in all 28 populations. Except for three African samples,
      the pairwise disequilibrium between the outermost RSP markers, TaqI "B" and "A",
      was highly significant with D' values greater than 0.8; in two of those
      exceptions the RSP marker was not polymorphic. Except for those same two African
      populations, the 16-repeat allele at the STRP also showed highly significant
      disequilibrium with the TaqI "B" site in all populations, with D' values usually
      greater than 0.7. Only four haplotypes account for more than 70% of all
      chromosomes in virtually all non-African populations, and two of those haplotypes
      account for more than 70% of all chromosomes in most East Asian and Amerindian
      populations. A new measure of the amount of overall disequilibrium shows least
      disequilibrium in African populations, somewhat more in European populations, and
      the greatest amount in East Asian and Amerindian populations. This pattern seems
      best explained by random genetic drift with low levels of recombination, a low
      mutation rate at the STRP, and essentially no recurrent mutation at the RSP
      sites, all in conjunction with an "Out of Africa" model for recent human
      evolution.

PMID- 9760209
TI  - Variation of site-specific methylation patterns in the factor VIII (F8C) gene in
      human sperm DNA.
AB  - The methylation status of 12 CpG sites in three exons of the human factor VIII
      (F8C) gene was examined by bisulphite genomic sequencing of human sperm DNA from
      14 European Caucasians and Asians. Different CpG sites were found to vary in
      their methylation status both within and between individuals. Strand differences
      in methylation status were also detected at certain sites, a finding that could
      reflect hemi-methylation. No evidence for systematic deviations in methylation
      status were found between the two ethnic groups. Only a limited correlation was
      observed between the level of methylation of specific CpG sites in sperm DNA and
      their mutability, a finding that is probably attributable to the pattern of
      methylation observed in mature spermatocytes not being representative of that of
      the germline.

PMID- 9760210
TI  - An ecological study of association between coronary heart disease mortality rates
      in men and the relative frequencies of common allelic variations in the gene
      coding for apolipoprotein E.
AB  - Three common alleles, epsilon2, epsilon3, and epsilon4, of the gene coding for
      apolipoprotein E (apoE) have been identified as predictors of interindividual
      variation in measures of lipid and lipoprotein metabolism, and ultimately risk of
      coronary heart disease (CHD), within many populations. Here we evaluated the
      utility of the geographic distribution of these alleles for prediction of
      interpopulation variation in average level of serum total cholesterol and other
      traditional risk factors, and CHD mortality rate. We employed published estimates
      of the relative frequencies of the three common apoE alleles, average levels of
      risk factors such as serum total cholesterol, systolic and diastolic blood
      pressure, body mass index, smoking prevalence and CHD mortality rate for nine
      population-based samples of middle-aged males studied by the international WHO
      MONICA Project. There was approximately a 10-fold difference between the highest
      and lowest CHD mortality rate. Of the traditional risk factors, variation in the
      average level of serum total cholesterol was the best predictor (approximately
      33%) of the observed interpopulation variation in estimates of CHD mortality rate
      (Pr=0.10). Variation in the relative frequency of the epsilon4 allele predicted
      approximately 50% of interpopulation variation in average serum total cholesterol
      level (Pr=0.02) and 75% of the variation in CHD mortality rate (Pr=0.002) when
      information about variation in the other risk factors and the epsilon2 and
      epsilon3 alleles is ignored. Furthermore, variation in the relative frequency of
      the epsilon4 allele predicted approximately 40% of the variation in CHD mortality
      rate (Pr=0.02) after considering the contribution of variation in average serum
      total cholesterol level. Average serum total cholesterol level was estimated to
      increase by 0.114 mmol/l (4.405 mg/dl), and CHD mortality rate by 24.5/100000,
      for an increase of 0.01 in the relative frequency of the epsilon4 allele. The
      predictive utility of the epsilon2 and epsilon3 alleles was considerably less
      than that of the epsilon4 allele. For the sample of populations considered, the
      geographic distribution of the apoE alleles can be a statistically significant
      predictor of interpopulation variation in both the average serum total
      cholesterol level and CHD mortality rate. In particular, the epsilon4 allele may
      confer valuable ecological risk information.

PMID- 9760212
TI  - Molecular characterization and mutational analysis of the human B17 subunit of
      the mitochondrial respiratory chain complex I.
AB  - Bovine NADH:ubiquinone oxidoreductase (complex 1) of the mitochondrial
      respiratory chain consists of about 36 nuclear-encoded subunits. We review the
      current knowledge of the 15 human complex I subunits cloned so far, and report
      the 598-bp cDNA sequence, the chromosomal localization and the tissue expression
      of an additional subunit, the B17 subunit. The cDNA open reading frame of B17
      comprises 387 bp and encodes a protein of 128 amino acids (calculated Mr 15.5
      kDa). There is 82.7% and 78.1% homology, respectively, at the cDNA and amino acid
      level with the bovine counterpart. The gene of the B17 subunit has been mapped to
      chromosome 2. Multiple-tissue dot-blots showed ubiquitous expression of the mRNA
      with relatively higher expression in tissues known for their high energy demand.
      Of these, kidney showed the highest expression. Mutational analysis of the
      subunit revealed no mutations or polymorphisms in 20 patients with isolated
      enzymatic complex I deficiency in cultured skin fibroblasts.

PMID- 9760211
TI  - Genotype/phenotype correlation in affected individuals of a family with a
      deletion of the entire coding sequence of the connexin 32 gene.
AB  - X-linked Charcot-Marie-Tooth disease (CMTX) is a peripheral nerve disorder that
      has been linked to mutations in the connexin 32 gene (Cx32). These mutations have
      been shown to be genetically heterogeneous, though recurrences of specific
      mutations in apparently unrelated families have been seen. The majority of
      mutations have been shown to be missense, resulting in non-conservative amino
      acid changes. A few mutations resulting in a premature termination of protein
      translation, including both nonsense mutations as well as frameshifting
      microdeletions, have been documented. We would like to report a deletion mutation
      that appears to eliminate the entire coding sequence of the Cx32 gene, but which
      has been shown to segregate with a clinical phenotype not unlike that seen in
      individuals with a less severe alteration of the Cx32 gene. The causes at a
      cellular level of the CMTX phenotype are still not fully clear, though there has
      been speculation that these may involve a dominant negative effect where the
      mutant connexin 32 suppresses the function of other connexins. Studies of
      kindreds such as this, where in CMTX-affected males the Cx32 gene product is
      totally absent, will help us to better understand the molecular mechanisms
      underlying the clinical phenotype associated with this disorder.

PMID- 9760213
TI  - The last 25 years -- the most highly cited papers.

PMID- 9760214
TI  - From absolute to exquisite specificity. Reflections on the fuzzy nature of
      species, specificity and antigenic sites.
AB  - The term specificity is derived from the word species and shares with it an
      inherent fuzziness based on the absence of sharp boundaries between closely
      related entities. Antibody specificity is a ternary relational property which
      refers to the antibody's capacity to discriminate between two or more epitopes.
      There are no sharp boundaries between the individual overlapping epitopes that
      constitute an antigenic site and there is also no clear-cut minimum difference in
      binding affinity or in atomic positions at the epitope-paratope interface that
      can serve as a yardstick for deciding that two epitopes or two paratopes are the
      same or not. Immunology shares with the whole of empirical science the need to
      handle fuzzy sets and concepts and this poses no threat to the unabated further
      development of immunochemical analysis.

PMID- 9760216
TI  - Computational models in immunological methods: an historical review.
AB  - The utilization of computational models in immunology dates from the birth of the
      science. From the description of antibody-antigen binding to the structural
      models of receptors, models are utilized to bring fundamental understandings of
      the processes together with laboratory measurements to uncover implications of
      these data. In this review, an historical view of the role of computational
      models in the immunology laboratory is presented, and short mathematical
      descriptions are given of fundamental assays. In addition, the range of current
      uses of models is explored -- especially as seen through papers which have
      appeared in the Journal of Immunological Methods from volume 1 (1971/1972) to
      volume 208 (1997). Each paper which introduced a new mathematical, statistical,
      or computer simulation model, or introduced an enhancement to an instrument
      through a model in those volumes is cited and the type of computational model
      noted.

PMID- 9760215
TI  - The increasing power of immunohistochemistry and immunocytochemistry.
AB  - Since its introduction in the early 1940s, immunostaining technology has
      developed in a remarkable way, and the applicability of immunohisto/cytochemical
      probing methods will unquestionably continue to increase in several directions.
      Immunofluorescence remains the most powerful and reliable immunohistochemical
      approach for multicolour staining to evaluate co-localization of two or more
      antigens in an objective manner. Moreover, the fluorescent colour signals exhibit
      a relatively consistent relationship to the actual antigen concentration in the
      test preparation and are hence better suited for quantitative computerized image
      analysis than light-microscopic observations of immunoenzyme staining. On the
      other hand, immunoenzyme methods are more economical with regard to reagent
      consumption and are therefore ideal for the use in semiautomatic staining
      machines. In addition, the superior morphological correlate provided by the
      latter methods, makes them more attractive and adequate for most purposes in
      diagnostic pathology laboratories. However, multicolour immunoenzyme staining
      provides an easily obtainable and reliable result only when the antigens are
      known a priori to be separately located, both because of technical problems and
      because imbalanced colour mixing is difficult to evaluate in the light
      microscope. All these aspects of immunohistochemistry are briefly reviewed in
      this historical perspective coloured by the author's own experience.

PMID- 9760217
TI  - Developments in immunological standardization.
AB  - In the century since Paul Erlich's innovative immunological standardization work
      with diphtheria anti-toxin, the field of immunological standardization has
      expanded dramatically. Biological standards for a diverse range of immunological
      substances have been produced e.g. immunoglobulins, complement components,
      autoantibodies and blood group reagents. The concept of calibration of such
      materials in biological units of potency is now widely accepted for many such
      substances. Most recently much effort has been devoted to producing biological
      standards for cytokines which can be used to calibrate and validate biological
      assays for these analytes. Immunoassays have been found to be particularly
      problematical from the standardization view point although provision of a single
      international standard for distribution world-wide is clearly advantageous and
      helps reduce assay variability. It is hoped that the considerable progress with
      immunological standardization achieved during the past century will continue and
      expand to ensure the validity of existing and new immunological assays which will
      be required in the future.

PMID- 9760218
TI  - WHO cytokine standardization: facilitating the development of cytokines in
      research, diagnosis and as therapeutic agents.
AB  - The development and widespread application of recombinant DNA technology has
      dramatically increased the number of cytokines available for clinical evaluation.
      New and novel cytokines are being discovered, cloned and entered into clinical
      trials at such a rate that it is often the case that the biological activities of
      these proteins are poorly understood during their development as therapeutic
      agents. In addition, manufacturers of any one cytokine can produce the protein
      from different cellular sources resulting in materials that exhibit markedly
      different specific activities. When estimating the amount of biological activity
      of different preparations with different specific activities by bioassay, mass
      units cannot be used and biological activity is therefore expressed as
      'biological potency units'. The biological unit requires definition by a standard
      that is assay-independent (especially when measuring a particular type of
      biological activity). In many cases, a variety of assay methods will be available
      and the material chosen for a standard should ideally be suitable for use with as
      many of them as possible. Once the unit is defined, this can be used in any
      laboratory, thus providing a means of ensuring uniformity throughout the world in
      the designation of potency of different biological preparations. The World Health
      Organisation (WHO) standardization programme involves the production of
      biologically stable, well characterised potency and immunoassay standards that
      are available world-wide using a single international unitage. Over the years,
      WHO international standards have been used to dramatically reduce the variation
      in estimates of cytokine preparations within and between laboratories for
      immunoassays and bioassays. WHO international standards are primary reference
      preparations against which secondary, or working standards (including regional
      standards, national standards, pharmacopoeial standards and in-house working
      standards) can be calibrated.

PMID- 9760219
TI  - Self-reactive antibodies (natural autoantibodies) in healthy individuals.
AB  - Antibodies that are present in the serum of healthy individuals in the absence of
      deliberate immunization with any antigen, are refered to as natural antibodies. A
      vast majority of natural antibodies react with one or more self antigens and are
      termed as natural autoantibodies. The importance of natural autoantibodies in
      immune regulation has long been neglected, since tolerance to self was thought to
      be primarily dependent on the deletion of autoreactive clones, rather than on
      peripheral suppressive mechanisms. Clonal deletion and energy cannot account,
      however, for the prevalence of natural autoreactivity among healthy individuals.
      It is now well established that autoreactive antibodies and B cells, and
      autoreactive T cells, are present in healthy individuals, and in virtually all
      vertebrate species. Autoreactive repertoires are predominantly selected early in
      ontogeny. Questions pertaining to the role of natural antibodies in the
      regulation of the immune response and maintenance of immune homeostasis and to
      the distinction between natural autoreactivity and pathological autoimmunity have
      not been adequately addressed. Here, we focus on the current knowledge on the
      physicochemical and functional properties of NAA in man, and the use of NAA for
      therapeutic intervention. reserved.

PMID- 9760221
TI  - Use of explant technology in the study of in vitro immune responses.
AB  - The establishment of in vitro culture systems provides an accessible means to
      study events within the immune system. In contrast to either dispersed suspension
      or two-dimensional monolayer culture, the explantation of tissue fragments under
      organ culture conditions is, to date, the only method which allows essential
      three-dimensional cellular interactions to be maintained under conditions which
      permit controlled experimental manipulation in vitro. Recent modifications of
      explant technology, particularly within the area of fetal thymic organ culture,
      now allow the controlled reassociation of defined cellular subsets and
      manipulation of gene expression, under conditions where the functioning of both
      lymphoid and stromal cell types closely resembles that in vivo.

PMID- 9760220
TI  - Assays of leukocyte locomotion and chemotaxis.
AB  - This review discusses the range of methods which are currently available for
      measuring locomotion and chemotaxis of leukocytes in vitro, their history, and
      some definitions of terms. Assays of the net migration of large cell populations,
      such as the filter assay are the most popular and are useful for identifying
      chemoattractant molecules, but give no direct information about how these
      molecules influence the speed and direction of cell movement (chemokinesis and
      chemotaxis). Visual assays including measures of orientation in gradients and
      time-lapse filming give detailed information about cell paths and direct evidence
      for chemotaxis and chemokinesis. The polarization assay is a useful visual
      screening assay. Assays which simulate the situation in living tissues are
      becoming more popular and include migration through collagen or fibrin gels or
      through monolayers of vascular endothelium. Locomotion is a complex process, no
      single assay gives full information and the use of more than one assay is
      recommended.

PMID- 9760222
TI  - Antibody engineering: comparison of bacterial, yeast, insect and mammalian
      expression systems.
AB  - Engineered antibody molecules, and their fragments, are being increasingly
      exploited as scientific and clinical tools. However, one factor that can limit
      the applicability of this technology is the ability to express large amounts of
      active protein. In this review we describe the relative advantages and
      disadvantages of bacterial, yeast, insect and mammalian expression systems, and
      discuss some of the problems that can be encountered when using them. There is no
      'universal' expression system, that can guarantee high yields of recombinant
      product, as every antibody-based molecule will pose its own problems in terms of
      expression. As a result the choice of system will depend on many factors,
      including the molecular species being expressed, the precise sequence of the
      individual antibody and the preferences of the individual investigator. However,
      there are general rules with regards to the design of expression vectors and
      systems which will help the investigator to make informed choices as to which
      strategy might be appropriate for their application.

PMID- 9760223
TI  - Recommendations for prevention and control of tuberculosis among foreign-born
      persons. Report of the Working Group on Tuberculosis among Foreign-Born Persons.
      Centers for Disease Control and Prevention.
AB  - During 1986-1997, the number of tuberculosis (TB) cases among foreign-born
      persons in the United States increased by 56%, from 4,925 cases (22% of the
      national total) to 7,702 cases (39% of the national total). As the percentage of
      reported TB cases among foreign-born persons continues to increase, the
      elimination of TB in the United States will depend increasingly on the
      elimination of TB among foreign-born persons. On May 16-17, 1997, CDC convened a
      working group of state and city TB-control program staff, as well as
      representatives from CDC's Division of TB Elimination and Division of Quarantine,
      to outline problems and propose solutions for addressing TB among foreign-born
      persons. The Working Group on Tuberculosis Among Foreign-Born Persons considered
      a) epidemiologic profiles of TB cases among foreign-born persons, b) case
      finding, screening, and preventive therapy for the foreign born, c) TB diagnosis
      and management for the foreign born, d) opportunities for collaborations with
      community-based organizations (CBOs) to address TB among the foreign born, and e)
      TB-related training needs. The Working Group's deliberations and the resulting
      recommendations for action by federal agencies, state and local TB-control
      programs, CBOs, and private health-care providers form the basis of this report.
      For each of the five topics of discussion, the group identified key issues,
      problems, and constraints and suggested solutions in the form of recommendations,
      which are detailed in this report. The Working Group made the following
      recommendations: * The epidemiology of TB among foreign-born populations differs
      considerably from area to area. To tailor TB-control efforts to local needs, TB
      control programs should develop epidemiologic profiles to identify groups of
      foreign-born persons in their jurisdictions who are at high risk for TB. * The
      priorities of TB control among the foreign born should be the same as those for
      control of TB among other U.S. populations - completion of treatment by persons
      infected with active TB, contact tracing, and screening and provision of
      preventive therapy for groups at high risk. Screening and preventive therapy
      should be limited to areas where completion of therapy rates and contact-tracing
      activities are currently adequate. * Based on local epidemiologic profiles,
      selective screening should be conducted among populations identified as being at
      high risk for TB. Screening should target groups of persons who are at the
      highest risk for TB infection and disease, accessible for screening, and likely
      to complete preventive therapy. The decision to screen for infection, disease, or
      both should be based on the person's age and time in the United States, prior
      screening, and locally available resources for the provision of preventive
      therapy. * TB-control programs should direct efforts towards identifying
      impediments to TB diagnosis and care among local foreign-born populations,
      devising strategies to address these barriers, and maximizing activities to
      ensure completion of treatment. * Providing TB preventive therapy and other TB
      related services for foreign-born persons is often impeded by linguistic,
      cultural, and health-services barriers. TB-control programs can help overcome
      these barriers by establishing partnerships with CBOs and by strengthening
      training and education efforts. Collaborations with health-service CBOs should
      center on developing more complementary roles, more effective coordination of
      services, and better use of existing resources for serving the foreign born. TB
      related training should be linked to overall TB-control strategies for the
      foreign born. Training and education should be targeted to providers, patients,
      and community workers.

PMID- 9760224
TI  - Bernstein's dynamic view of the brain: the current problems of modern
      neurophysiology (1945).

PMID- 9760225
TI  - Crystal structure and possible dimerization of the high-potential iron-sulfur
      protein from Chromatium purpuratum.
AB  - The crystal structure of the high-potential iron-sulfur protein (HiPIP) isolated
      from Chromatium purpuratum is reported at 2.7 A resolution. The three HiPIP
      molecules in the asymmetric unit of the crystals form one and one-half dimers.
      Two molecules are related by a noncrystallographic symmetry rotation of
      approximately 175 degrees with negligible translation along the dyad axis. The
      third molecule in the asymmetric unit also forms a dimer with a second HiPIP
      molecule across the crystallographic 2-fold symmetry axis. The Fe4S4 clusters in
      both the crystallographic and noncrystallographic dimers are separated by
      approximately 13.0 A. Solution studies give mixed results regarding the
      oligomeric state of the C. purpuratum HiPIP. A comparison with crystal structures
      of HiPIPs from other species shows that HiPIP tends to associate rather
      nonspecifically about a conserved, relatively hydrophobic surface patch to form
      dimers.

PMID- 9760226
TI  - Possible arrangement of the five domains in human complement factor I as
      determined by a combination of X-ray and neutron scattering and homology
      modeling.
AB  - Human factor I is a multidomain plasma serine protease with one factor I-membrane
      attack complex (FIMAC) domain, one CD5 domain, two low-density lipoprotein
      receptor (LDLr) domains, and one serine protease (SP) domain and is essential for
      the regulation of complement. The domain arrangement in factor I was determined
      by X-ray and neutron scattering on serum-derived human factor I (sFI) and
      recombinant insect cell factor I (rFI). While the radii of gyration of both were
      the same at 4.05 nm and both had overall lengths of 14 nm, the cross-sectional
      radii of gyration were different at 1.70 nm for sFI and 1.57 nm for rFI. This
      difference was attributed to their different means of glycosylation which is
      complex-type for sFI and high-mannose-type for rFI. Homology models were
      constructed for the FIMAC, LDLr, and SP domains of factor I using related crystal
      structures, and CD5 was represented as a globular protein by referencing its
      electron microscopy dimensions. In these models, 38 of the 40 Cys residues in
      factor I were predicted to form internal disulfide bridges. The two remaining Cys
      residues at the N terminus of the FIMAC domain and at the center of the first
      LDLr domain were potentially not bridged. It was postulated that, if these two
      Cys residues were bridged to each other, the FIMAC, CD5, and LDLr-1 domains would
      form a compact triangular arrangement. This hypothesis was tested by automated
      scattering curve fit searches based on 9600 bilobal models, setting the FIMAC,
      CD5, and LDLr-1 domains as one lobe and the large SP domain as the other lobe.
      The searches gave a single small family of similar structures with a separation
      of 5.9 nm between the centers of the lobes which gave similar good X-ray and
      neutron fits for both sFI and rFI, despite the different glycosylations of sFI
      and rFI. These best-fit structures for factor I showed that this domain model is
      plausible, and suggested that the SP and the CD5 and LDLr-1 domains may present
      exposed surfaces in factor I whose roles are to interact separately with its
      substrates C3b and C4b and with cofactor proteins.

PMID- 9760228
TI  - Residues critical for formylglycine formation and/or catalytic activity of
      arylsulfatase A.
AB  - Sulfatases contain a unique posttranslational modification in their active site,
      a formylglycine residue generated from a cysteine or a serine residue. The
      formylglycine residue is part of a sequence that is highly conserved among
      sulfatases, suggesting that it might direct the generation of this unique amino
      acid derivative. In the present study residues 68-86 flanking formylglycine 69 in
      arylsulfatase A were subjected to an alanine/glycine scanning mutagenesis. The
      mutants were analyzed for the conversion of cysteine 69 to formylglycine and
      their kinetic properties. Only cysteine 69 turned out to be essential for
      formation of the formylglycine residue, while substitution of leucine 68, proline
      71, and alanine 74 within the heptapeptide LCTPSRA reduced the formylglycine
      formation to about 30-50%. Several residues that are part of or directly adjacent
      to an alpha-helix presenting the formylglycine 69 at the bottom of the active
      site pocket were found to be critical for catalysis. A surprising outcome of this
      study was that a number of residues fully or highly conserved between all known
      eukaryotic and prokaryotic sulfatases turned out to be essential neither for
      generation of formylglycine nor for catalysis.

PMID- 9760227
TI  - Structural basis for the recognition of carbohydrates by human galectin-7.
AB  - Knowledge about carbohydrate recognition domains of galectins, formerly known as
      S-type animal lectins, is important in understanding their role(s) in cell-cell
      interactions. Here we report the crystal structure of human galectin-7 (hGal-7),
      in free form and in the presence of galactose, galactosamine, lactose, and N
      acetyl-lactosamine at high resolution. This is the first structure of a galectin
      determined in both free and carbohydrate-bound forms. The structure shows a fold
      similar to that of the prototype galectins -1 and -2, but has greater similarity
      to a related galectin molecule, Gal-10. Even though the carbohydrate-binding
      residues are conserved, there are significant changes in this pocket due to
      shortening of a loop structure. The monomeric hGal-7 molecule exists as a dimer
      in the crystals, but adopts a packing arrangement considerably different from
      that of Gal-1 and Gal-2, which has implications for carbohydrate recognition.

PMID- 9760229
TI  - Exploring a channel to the active site of copper/topaquinone-containing
      phenylethylamine oxidase by chemical modification and site-specific mutagenesis.
AB  - Copper amine oxidase contains an organic redox cofactor, 2,4, 5
      trihydroxyphenylalaninequinone (topaquinone, TPQ), derived by the post
      translational modification of a specific tyrosyl residue. To identify amino acid
      residues participating in the biogenesis of TPQ in the recombinant
      phenylethylamine oxidase from Arthrobacter globiformis, we have modified the
      copper/TPQ-less apoenzyme and the copper/TPQ-containing holoenzyme with 4-fluoro
      7-nitrobenzo-2-oxa-1, 3-diazole (NBD-F). In the apoenzyme modification, the Cu2+
      dependent, self-processing formation of the TPQ cofactor was retarded in
      accordance with the amount of NBD incorporated. The holoenzyme was also rapidly
      inactivated by incubation with NBD-F. The inactivation was prevented almost
      completely in the presence of an oxidation product from phenylethylamine,
      phenylacetaldehyde. Furthermore, the reaction of an inhibitor, phenylhydrazine,
      with TPQ was much slower in the NBD-labeled holoenzyme than in the native
      holoenzyme. Sequence analysis of the NBD-labeled holoenzyme has identified Lys184
      and Lys354 as the labeled sites. The two Lys residues are located close to the
      entrance to a channel, which has been found by recent X-ray crystallographic
      studies to be suitable for the movement of substrates and products to and from
      the Cu2+/TPQ-active site buried in the protein interior (Wilce, M. C. J., et al.
      (1997) Biochemistry 36, 16116-16133). However, site-specific mutant enzymes for
      Lys184, Lys354, and the neighboring invariant His355 had normal capacities for
      the TPQ formation in apoenzyme. These residues were also found to be dispensable
      for catalytic activity of holoenzyme. Thus, modification of Lys184 and Lys354
      with NBD-F presumably causes structural perturbations of the substrate channel or
      steric hindrance for the access of small molecules to the active site through the
      channel.

PMID- 9760230
TI  - Nucleoside diphosphate kinase from bovine retina: purification, subcellular
      localization, molecular cloning, and three-dimensional structure.
AB  - The biochemical and structural properties of bovine retinal nucleoside
      diphosphate kinase were investigated. The enzyme showed two polypeptides of
      approximately 17.5 and 18.5 kDa on SDS-PAGE, while isoelectric focusing revealed
      seven to eight proteins with a pI range of 7.4-8.2. Sedimentation equilibrium
      yielded a molecular mass of 96 +/- 2 kDa for the enzyme. Carbohydrate analysis
      revealed that both polypeptides contained Gal, Man, GlcNAc, Fuc, and GalNac
      saccharides. Like other nucleoside diphosphate kinases, the retinal enzyme showed
      substantial differences in the Km values for various di- and triphosphate
      nucleotides. Immunogold labeling of bovine retina revealed that the enzyme is
      localized on both the membranes and in the cytoplasm. Screening of a retinal cDNA
      library yielded full-length clones encoding two distinct isoforms (NBR-A and NBR
      B). Both isoforms were overexpressed in Escherichia coli and their biochemical
      properties compared with retinal NDP-kinase. The structures of NBR-A and NBR-B
      were determined by X-ray crystallography in the presence of guanine
      nucleotide(s). Both isoforms are hexameric, and the fold of the monomer is
      similar to other nucleoside diphosphate kinase structures. The NBR-A active site
      contained both a cGMP and a GDP molecule each bound at half occupancy while the
      NBR-B active site contained only cGMP.

PMID- 9760231
TI  - Role of active site tyrosine residues in catalysis by human glutathione
      reductase.
AB  - Tyr114 and Tyr197 are highly conserved residues in the active site of human
      glutathione reductase, Tyr114 in the glutathione disulfide (GSSG) binding site
      and Tyr197 in the NADPH site. Mutation of either residue has profound effects on
      catalysis. Y197S and Y114L have 17% and 14% the activity of the wild-type enzyme,
      respectively. Mutation of Tyr197, in the NADPH site, leads to a decrease in Km
      for GSSG, and mutation of Tyr114, in the GSSG site, leads to a decrease in Km for
      NADPH. This behavior is predicted for enzymes operating by a ping-pong mechanism
      where both half-reactions partially limit turnover. Titration of the wild-type
      enzyme or Y114L with NADPH proceeds in two phases, Eox to EH2 and EH2 to EH2
      NADPH. In contrast, Y197S reacts monophasically, showing that excess NADPH fails
      to enhance the absorbance of the thiolate-FAD charge-transfer complex, the
      predominant EH2 form of glutathione reductase. The reductive half-reactions of
      the wild-type enzyme and of Y114L are similar; FAD reduction is fast
      (approximately 500 s-1 at 4 degreesC) and thiolate-FAD charge-transfer complex
      formation has a rate of 100 s-1. In Y197S, these rates are only 78 and 5 s-1,
      respectively. The oxidative half-reaction, the rate of reoxidation of EH2 by
      GSSG, of the wild-type enzyme is approximately 4-fold faster than that of Y114L.
      These results are consistent with Tyr197 serving as a gate in the binding of
      NADPH, and they indicate that Tyr114 assists the acid catalyst His467'.

PMID- 9760233
TI  - Conformational changes occurring upon reduction and NO binding in nitrite
      reductase from Pseudomonas aeruginosa.
AB  - Nitrite reductase (NiR) from Pseudomonas aeruginosa (EC 1.9.3.2) (NiR-Pa) is a
      soluble enzyme catalyzing the reduction of nitrite (NO2-) to nitric oxide (NO).
      The enzyme is a 120 kDa homodimer, in which each monomer carries one c and one d1
      heme. The oxidized and reduced forms of NiR from Paracoccus denitrificans GB17
      (previously called Thiosphaera pantotropha) (NiR-Pd) have been described [Fulop,
      V., et al. (1995) Cell 81, 369-377; Williams, P. A., et al. (1997) Nature 389,
      406-412], and we recently reported on the structure of oxidized NiR-Pa at 2.15 A
      [Nurizzo, D., et al. (1997) Structure 5, 1157-1171]. Although the domains
      carrying the d1 heme are almost identical in both NiR-Pa and NiR-Pd oxidized and
      reduced structures, the c heme domains show a different pattern of c heme
      coordination, depending on the species and the redox state. The sixth d1 heme
      ligand in oxidized NiR-Pd was found to be Tyr25, whereas in NiR-Pa, the
      homologuous Tyr10 does not interact directly with Fe3+, but via a hydroxide ion.
      Furthermore, upon reduction, the axial ligand of the c heme of NiR-Pd changes
      from His17 to Met108. Finally, in the oxidized NiR-Pa structure, the N-terminal
      stretch of residues (1-29) of one monomer interacts with the other monomer
      (domain swapping), which does not occur in NiR-Pd. Here the structure of reduced
      NiR-Pa is described both in the unbound form and with the physiological product,
      NO, bound at the d1 heme active site. Although both structures are similar to
      that of reduced NiR-Pd, significant differences with respect to oxidized NiR-Pd
      were observed in two regions: (i) a loop in the c heme domain (residues 56-62) is
      shifted 6 A away and (ii) the hydroxide ion, which is the sixth coordination
      ligand of the heme, is removed upon reduction and NO binding and the Tyr10 side
      chain rotates away from the position adopted in the oxidized form. The
      conformational changes observed in NiR-Pa as the result of reduction are less
      extensive than those occurring in NiR-Pd. Starting with oxidized structures that
      differ in many respects, the two enzymes converge, yielding reduced conformations
      which are very similar to each other, which indicates that the conformational
      changes involved in catalysis are considerably diverse.

PMID- 9760232
TI  - Ligand-induced conformational change in transferrins: crystal structure of the
      open form of the N-terminal half-molecule of human transferrin.
AB  - Serum transferrin binds ferric ions in the bloodstream and transports them to
      cells, where they are released in a process involving receptor-mediated
      endocytosis. Iron release is believed to be pH dependent and is coupled with a
      large conformational change. To help define the steps in iron release, we have
      determined the three-dimensional structure of the iron-free (apo) form of the
      recombinant N-lobe half-molecule of human serum transferrin (ApoTfN) by X-ray
      crystallography. Two crystal forms were obtained, form 1 with four molecules in
      the asymmetric unit and form 2 with two molecules in the asymmetric unit. The
      structures of both forms were determined by molecular replacement and were
      refined at 2.2 and 3.2 A resolution, respectively. Final R-factors were 0.203
      (free R = 0. 292) for form 1 and 0.217 (free R = 0.312) for form 2. All six
      copies of the ApoTfN structure are essentially identical. Comparison with the
      holo form (FeTfN) shows that a large rigid-body domain movement of 63 degrees has
      occurred in ApoTfN, to give an open binding cleft. The extent of domain opening
      is the same as in the N-lobe of human lactoferrin, showing that it depends on
      internal constraints that are conserved in both proteins, and that it is
      unaffected by the presence or absence of the C-lobe. Although the conformational
      change is primarily a rigid-body motion, several local adjustments occur. In
      particular, two iron ligands, Asp 63 and His 249, change conformation to form
      salt bridges, with Lys 296 and Glu 83, respectively, in the binding cleft of the
      apo protein. Both salt bridges would have to break for iron coordination to
      occur. Most importantly, the structure, determined at a pH (5.3) that is close to
      the pH of physiological iron release, indicates that protonation of His 249 is a
      key step in iron release.

PMID- 9760234
TI  - Neutron-scattering studies reveal further details of the Ca2+/calmodulin
      dependent activation mechanism of myosin light chain kinase.
AB  - Previously, we utilized small-angle X-ray scattering and neutron scattering with
      contrast variation to obtain the first low-resolution structure of
      4Ca2+.calmodulin (CaM) complexed with a functional enzyme, an enzymatically
      active truncation mutant of skeletal muscle myosin light chain kinase (MLCK).
      These experiments showed that, upon binding to MLCK, CaM undergoes a
      conformational collapse identical to that observed when CaM binds to the isolated
      peptide corresponding to the CaM binding sequence of MLCK. CaM thereby was shown
      to release the inhibition of the kinase by inducing a significant movement of its
      CaM binding and autoinhibitory sequences away from the surface of the catalytic
      core [Krueger, J. K., Olah, G. A., Rokop, S. E., Zhi, G., Stull, J. T., and
      Trewhella, J. (1997) Biochemistry 36, 6017-6023]. We report here similar
      scattering experiments on the CaM.MLCK complex with the addition of substrates; a
      nonhydrolyzable analogue of adenosine-triphosphate, AMPPNP, and a peptide
      substrate for MLCK, a phosphorylation sequence from myosin regulatory light chain
      (pRLC). These substrates are shown to induce an overall compaction of the
      complex. The separation of the centers-of-mass of the CaM and MLCK components is
      shortened (by approximately 12 A), thus bringing CaM closer to the catalytic site
      compared to the complex without substrates. In addition, there appears to be a
      reorientation of CaM with respect to the kinase upon substrate binding that
      results in interactions between the N-terminal sequence of CaM and the kinase
      that were not observed in the complex without substrates. Finally, the kinase
      itself becomes more compact in the CaM.MLCK.pRLC.AMPPNP complex compared to the
      complex without substrates. This observed compaction of MLCK upon substrate
      binding is similar to that arising from the closure of the catalytic cleft in
      cAMP-dependent protein kinase upon binding pseudosubstrate.

PMID- 9760235
TI  - Mapping substrate-induced conformational changes in cAMP-dependent protein kinase
      by protein footprinting.
AB  - Upon binding of substrates the catalytic subunit (C) of cAMP-dependent protein
      kinase (cAPK) undergoes significant induced conformational changes that lead to
      catalysis. For the free apoenzyme equilibrium favors a more open and malleable
      conformation while the ternary complex of C, MgATP, and a 20-residue inhibitor
      peptide [PKI (5-24)] adopts a tight and closed conformation [Zheng, J., et al.
      (1993) Protein Sci. 2, 1559]. It is not clear that binding of either ligand alone
      is responsible for this conformational switch or whether both are required. In
      addition, the catalytic subunit binds MgATP and inhibitor peptide
      synergistically. The structural basis for this synergism is also not defined at
      present. Using an Fe-EDTA-mediated protein footprinting technique, the
      conformational changes associated with the binding of MgATP and the heat stable
      protein kinase inhibitor (PKI) were probed by mapping the solvent-accessible
      surface and structural dynamics of C. The conformation of the free enzyme was
      clearly distinguished from the ternary complex. Furthermore, binding of MgATP
      alone induced extensive conformational changes, both local and global, that
      include the glycine-rich loop, the linker connecting the small and large lobes,
      the catalytic loop, the Mg2+ positioning loop, the activation loop, and the F
      helix. These changes, similar to those seen in the ternary complex, are
      consistent with a transition from an open to a more closed conformation and
      likely reflect the motions that are associated with catalysis and product
      release. In contrast, the footprinting pattern of C.PKI resembled free C,
      indicating minimal conformational changes. Binding of MgATP, by shifting the
      equilibrium to a more closed conformation, "primes" the enzyme so that it is
      poised for the docking of PKI and provides an explanation for synergism between
      MgATP and PKI.

PMID- 9760236
TI  - Structural basis of the Tanford transition of bovine beta-lactoglobulin.
AB  - The structures of the trigonal crystal form of bovine beta-lactoglobulin variant
      A at pH 6.2, 7.1, and 8.2 have been determined by X-ray diffraction methods at a
      resolution of 2.56, 2. 24, and 2.49 A, respectively. The corresponding values for
      R (Rfree) are 0.192 (0.240), 0.234 (0.279), and 0.232 (0.277). The C and N
      termini as well as two disulfide bonds are clearly defined in these models. The
      glutamate side chain of residue 89 is buried at pH 6.2 and becomes exposed at pH
      7.1 and 8.2. This conformational change, involving the loop 85-90, provides a
      structural basis for a variety of pH-dependent chemical, physical, and
      spectroscopic phenomena, collectively known as the Tanford transition.

PMID- 9760237
TI  - Anionic binding site and 2,3-DPG effect in bovine hemoglobin.
AB  - It is generally believed that bovine hemoglobin (BvHb) interacts weakly with 2,3
      diphosphoglycerate (2,3-DPG) in a chloride-free media and not at all in the
      presence of physiological concentrations of chloride (100 mM). This lack of
      interaction has raised several questions at both structural and evolutionary
      levels. Results obtained in this study via 31P nuclear magnetic resonance (NMR)
      show that, even in the presence of 100 mM chloride ions, 2,3-DPG does, in fact,
      interact with bovine deoxy-Hb. This spectroscopic observation has been confirmed
      by oxygen binding experiments, which have also shown that, under certain
      conditions, chloride and 2,3-DPG may display a synergistic effect in modifying
      the oxygen affinity of bovine hemoglobin. It could be that this synergistic
      effect has its structural basis in a conformational modification induced by 2,3
      DPG, possibly causing extra chloride anions to approach the positive charges
      which constitute the anion binding site. Another possibility, not necessarily an
      alternative, is the additional chloride binding site recently identified
      [Fronticelli, C., Sanna, M. T., Perez-Alvarado, G. C., Karavitis, M., Lu, A.-L.,
      and Brinnigar, W. S. (1995) J. Biol. Chem 270, 30588-30592] involving lysine
      beta76 that in bovine Hb substitutes for the alanine residue present in human
      hemoglobin. All of these findings are in agreement with the very low enthalpy of
      oxygenation that characterizes bovine Hb when both chloride and 2,3-DPG are
      present in concomitance. The results reported here clearly show that bovine
      hemoglobin does react with 2, 3-DPG and is functionally affected by this organic
      phosphate. Hence, the very low intraerythrocytic concentration of 2,3-DPG (0.5
      mM) in adult bovine red blood cells is the result of metabolic adaptation which
      cannot be explained solely by the different amino acid sequence at the level of
      the 2,3-DPG binding site.

PMID- 9760238
TI  - Identification of the binding surface on Cdc42Hs for p21-activated kinase.
AB  - The Ras superfamily of GTP-binding proteins is involved in a number of cellular
      signaling events including, but not limited to, tumorigenesis, intracellular
      trafficking, and cytoskeletal organization. The Rho subfamily, of which Cdc42Hs
      is a member, is involved in cell morphogenesis through a GTPase cascade which
      regulates cytoskeletal changes. Cdc42Hs has been shown to stimulate DNA synthesis
      as well as to initiate a protein kinase cascade that begins with the activation
      of the p21-activated serine/threonine kinases (PAKs). We have determined
      previously the solution structure of Cdc42Hs [Feltham et al. (1997) Biochemistry
      36, 8755-8766] using NMR spectroscopy. A minimal-binding domain of 46 amino acids
      of PAK was identified (PBD46), which binds Cdc42Hs with a KD of approximately 20
      nM and inhibits GTP hydrolysis. The binding interface was mapped by producing a
      fully deuterated sample of 15N-Cdc42Hs bound to PBD46. A 1H,15N-NOESY-HSQC
      spectrum demonstrated that the binding surface on Cdc42Hs consists of the second
      beta-strand (beta2) and a portion of the loop between the first alpha-helix
      (alpha1) and beta2 (switch I). A complex of PBD46 bound to 15N-Cdc42Hs.GMPPCP
      exhibited extensive chemical shift changes in the 1H,15N-HSQC spectrum. Thus,
      PBD46 likely produces structural changes in Cdc42Hs which are not limited to the
      binding interface, consistent with its effects on GTP hydrolysis. These results
      suggest that the kinase-binding domain on Cdc42Hs is similar to, but more
      extensive than, the c-Raf-binding domain on the Ras antagonist, Rap1 [Nassar et
      al. (1995) Nature 375, 554-560)].

PMID- 9760239
TI  - Activation of methylesterase CheB: evidence of a dual role for the regulatory
      domain.
AB  - The response regulator CheB functions within the bacterial chemotaxis system
      together with the methyltransferase CheR to control the level of chemoreceptor
      methylation, influencing the signaling activities of the receptors. CheB
      catalyzes demethylation of specific methylglutamate residues introduced into the
      chemoreceptors by CheR. CheB has a two-domain architecture consisting of an N
      terminal regulatory domain joined by a linker to a C-terminal effector domain. In
      the unphosphorylated state of the response regulator, the regulatory domain
      inhibits the methylesterase activity of the effector domain. Upon phosphorylation
      of a specific aspartate residue within the regulatory domain, the C-terminal
      methylesterase activity is stimulated, resulting in the subsequent demethylation
      of the chemoreceptors. We have investigated the mechanism of regulation of CheB
      activity by the N-terminal regulatory domain. First, we have found that
      phosphorylation of the N-terminal domain not only relieves inhibition of the C
      terminal methylesterase activity but also provides an enhancement of this
      activity above that seen for the C-terminal effector domain alone. Second, we
      have identified mutations in CheB that show an enhancement of methylesterase
      activity in the absence of phosphorylation. Most of these single-site mutations
      are localized in the linker region joining the regulatory and effector domains.
      On the basis of these observations, we propose a model for activation of CheB in
      which phosphorylation of the regulatory domain results in a reorganization of the
      domain interface, allowing exposure of the active site to the receptor substrate
      and simultaneously stimulating methylesterase activity.

PMID- 9760240
TI  - Solution structure of the catalytic domain of human stromelysin-1 complexed to a
      potent, nonpeptidic inhibitor.
AB  - The full three-dimensional structure of the catalytic domain of human stromelysin
      1 (SCD) complexed to a novel and potent, nonpeptidic inhibitor has been
      determined by nuclear magnetic resonance spectroscopy (NMR). To accurately mimic
      assay conditions, the structure was obtained in Tris buffer at pH 6.8 and without
      the presence of organic solvent. The results showed that the major site of enzyme
      inhibitor interaction occurs in the S1' pocket whereas portions of the inhibitor
      that occupy the shallow S2' and S1 pockets remained primarily solvent exposed.
      Because this relatively small inhibitor could not deeply penetrate stromelysin's
      long narrow hydrophobic S1' pocket, the enzyme was found to adopt a dramatic fold
      in the loop region spanning residues 221-231, allowing occupation of the solvent
      accessible S1' channel by the enzyme itself. This remarkable conformational fold
      at the enzyme binding site resulted in constriction of the S1' loop region about
      the inhibitor. Examination of the tertiary structure of the stromelysin-inhibitor
      complex revealed few hydrogen-bonding or hydrophobic interactions between the
      inhibitor and enzyme that can contribute to overall binding energy; hence the
      resultant compact structure may in part account for the relatively high potency
      exhibited by this inhibitor.

PMID- 9760241
TI  - Site-directed mutants of rat testis fructose 6-phosphate, 2-kinase/fructose 2,6
      bisphosphatase: localization of conformational alterations induced by ligand
      binding.
AB  - Site-directed mutagenesis was utilized to construct mutants, containing one or
      two tryptophan residues, of the bifunctional enzyme fructose 6-phosphate,2-kinase
      fructose 2,6-bisphosphatase. Two of the single-tryptophan mutants (W15 and W64)
      had the tryptophan residue located in the kinase domain, which is in the N
      terminal half, and two (W299 and W320) had the tryptophan residue located in the
      phosphatase domain, which is in the C-terminal half. The double-tryptophan
      mutants were W15/W64, W15/W299, W64/W299, and W299/W320. Dynamic polarization
      data indicated that these tryptophan residues had varying degrees of local
      mobility. Steady-state polarization data revealed energy transfer between the
      tryptophan residues in the double mutant W299/W320 but not in the W15/W64,
      W15/W299, or W64/W299 mutants, indicating the proximity of the W299 and W320
      residues. The binding of fructose-6-phosphate resulted in a significant increase
      in the anisotropy of the W15 mutants, but did not affect the anisotropies of any
      of the other single-tryptophan mutants. Binding of fructose-2,6-bisphosphate also
      significantly increased the anisotropy of W15. In the case of fructose-6
      phosphate binding, the increased anisotropy was shown to be due to a restriction
      of the tryptophan residue's local mobility in the presence of bound ligand, which
      suggests that the N-terminus is located near the kinase active site. These
      increases in anisotropies were used to estimate the dissociation constants of
      fructose-6-phosphate and fructose-2,6-bisphosphate, which were 29 +/- 3 and 2.1
      +/- 0.3 microM, respectively. These observations are considered in light of the
      recently published crystal structure for this bifunctional enzyme.

PMID- 9760242
TI  - The enzymatic properties of Octopus vulgaris hemocyanin: o-diphenol oxidase
      activity.
AB  - Hemocyanin and tyrosinase are dinuclear copper proteins capable of reversibly
      binding dioxygen. Despite the great similarity of structure and properties of
      their active site, the two proteins perform different biological functions
      (oxygen transport/storage versus monooxygenase and oxidase activity). In this
      paper, we show that Octopus vulgaris hemocyanin exhibits a tyrosinase-like
      activity; namely, it is capable of utilizing dioxygen for the oxidation of o
      diphenol to quinone. The reaction is specific for this isomer of diphenol, the
      meta and para isomers being unreactive, and is strongly controlled by steric
      factors. Dioxygen represents a cosubstrate of the reaction, and it is involved in
      the catalytic turnover by binding to the dinuclear copper site of the protein to
      form, under steady-state conditions, oxy-Hc, which is the active species. The
      generation of semiquinone radicals, detected by EPR and by their reaction with
      N,N,N',N'-tetramethyl-1,4-phenylenediamine, strongly supports a reaction
      mechanism in which such radicals represent the reaction products of one-electron
      oxidation of the substrate, quinone being generated by dismutation of
      semiquinones. Met-Hc is regenerated by the substrate to the deoxy form. To close
      the catalytic cycle, the proposed reaction mechanism also involves the
      participation of two transient protein forms with the total oxidation state of
      the active site (V and IV) intermediate between that of oxy-Hcy, [CuIIO22
      CuII]VI, and deoxy-Hc, [CuICuI]II. A mathematical model has been elaborated to
      describe the reaction kinetics. The differences in reaction mechanisms between
      hemocyanin and tyrosinase are discussed in terms of accessibility to exogenous
      molecules of their active sites.

PMID- 9760243
TI  - Transactivation of the ApoCIII promoter by ATF-2 and repression by members of the
      Jun family.
AB  - It was shown previously that cytokines such as tumor necrosis factor-alpha that
      stimulate signal transduction pathways involving transcription factors ATF-2 and
      Jun repress apoCIII promoter activity in HepG2 cells. In the present study, DNase
      I footprinting analysis established that ATF-2 protected three regions in the
      apoCIII promoter. One region (-747/-726) present in the apoCIII enhancer is
      within the previously identified footprint I and has overlapping boundaries with
      the binding sites of Sp1 (-764/-742) and HNF-4 (-736/-714). The other two regions
      represent new footprints and have been designated D/E (-219/-199) and B/C (-102/
      75). The B/C region overlaps with the previously identified footprint B which
      contains an HNF-4 binding site (-87/-63). Cotransfection experiments in HepG2
      cells showed that ATF-2 transactivated the -890/+24 apoCIII promoter 1.6-fold. In
      addition, mutations in the proximal D/E (-219/-199) and distal I (-747/-726) ATF
      2-binding sites reduced the apoCIII promoter strength to 33 and 9% of control,
      respectively, indicating that ATF-2 is a positive regulator of apoCIII gene
      transcription. Cotransfections with ATF-2 and HNF-4 expression plasmids resulted
      in additive transactivation of the apoCIII promoter. Furthermore, apoCIII
      promoter constructs bearing mutations in the D/E and I ATF-2 binding sites were
      efficiently transactivated by HNF-4, suggesting that these two factors contribute
      independently to the apoCIII promoter strength. Members of the Jun family (c-Jun,
      JunB, and JunD) caused a dose-dependent inhibition of the -890/+24 apoCIII
      promoter activity. A synthetic promoter containing the apoCIII enhancer in front
      of the minimal AdML promoter was also repressed by Jun. In contrast, apoCIII
      promoter segments lacking the enhancer region were transactivated by Jun. The
      findings suggest that homodimers of Jun or heterodimers of Jun with other AP-1
      subunits could be responsible for the observed repression by interfering with the
      function(s) of the apoCIII enhancer. Repression by Jun could be reversed in the
      presence of ATF-2 and HNF-4, suggesting that ATF2 and possibly Jun/ATF-2
      heterodimers exert a positive effect on apoCIII gene transcription, as opposed to
      Jun homodimers or heterodimers with other AP-1 members. These findings suggest a
      role for members of the Jun family and ATF-2 that participate in signal
      transduction pathways in basal or induced apoCIII promoter activity in cells of
      hepatic origin.

PMID- 9760244
TI  - Photoaffinity labeling of homologous Met-133 and Met-139 amino acids of rabbit
      and sheep sex hormone-binding globulins with the unsubstituted Delta 6
      testosterone photoreagent.
AB  - Purified rabbit and sheep sex hormone-binding globulins (SHBGs) were photolabeled
      by Delta 6-testosterone. The maximal levels of specific incorporation were
      respectively 0.33 and 0.30 mol of label/mol of homodimer. Tryptic cleavage of
      photolabeled SHBGs gave a single radioactive peptide for rabbit SHBG and two
      major radioactive peptides S1 and S2 for sheep SHBG. Edman sequencing of the
      photolabeled peptide of rabbit SHBG revealed a single sequence corresponding to
      peptidic fragment Leu-118-Lys-134. Subcleavage of this peptide with elastase led
      to a single radioactive peptidic fragment corresponding to dipeptide Met-133-Lys
      134, identified by mass spectrometry, while deletion of the C-terminal residue
      with carboxypeptidase B showed that all the radioactivity remained on peptide Leu
      118-Met-133, thus demonstrating that photolabeling occurred exclusively on Met
      133, the only residue common to the two radioactive subcleaved peptides. Edman
      sequencing of peptides S1 and S2 of sheep SHBG showed a same single sequence
      corresponding to residues Gln-126-Arg-140 which contained no identifiable
      phenylthiohydantoin derivative at cycle 14, thus indicating that in both cases
      the corresponding Met-139 residue is the main site of photolabeling, as confirmed
      for peptide S1 by the presence at this cycle of a major peak of radioactivity
      while in peptide S2 the photoattachment of Delta 6-testosterone was found labile
      in the conditions of sequencing. The photolabeled peptide S1 was characterized by
      mass spectrometry which showed the covalent fixation of one mole of Delta 6
      testosterone and the presence of a biantennary oligosaccharide attached at Asn
      133, which suggests that the steroid-binding site is probably not deeply buried
      in the SHBG homodimer.

PMID- 9760245
TI  - The dimerization domain of potato spindle tuber viroid, a possible hallmark for
      infectious RNA.
AB  - Covalently closed circular (+) RNA of the potato spindle tuber viroid (PSTVd) can
      efficiently dimerize noncovalently upon heating and slow cooling in the presence
      of monovalent cations or Mg2+. In vitro transcription of subgenomic fragments
      reveals that the ability to dimerize resides in the "upper strand" of its self
      complementary rod-like structure. Nuclease probing of these fragments, namely,
      molecules spanning either the upper or the lower strand of PSTVd, confirms the
      existence of the previously proposed hairpins I-III, of which hairpin I might
      contain noncanonical G.A and A.A base pairs. In addition, the upper and lower (+)
      strands contain large hairpin loops consisting of stretches rich in either
      adenosine or uridine. Dimerization of the upper (+) strand results in a nuclease
      resistant core encompassing hairpin I and is inhibited by an antisense
      oligonucleotide spanning the entire hairpin; this palindromic domain thus
      represents the dimerization site. When upper and lower strands were heated and
      cooled together, no annealing to a viroid-like duplex of both molecules occurs,
      only dimerization of the upper strand. Therefore, the dimerization hairpin of
      viroid RNA represents a unique conformational signal that is homologous to
      similar regions in the human immunodeficiency virus and other retroviruses.

PMID- 9760246
TI  - Structure and mucoadhesion of mussel glue protein in dilute solution.
AB  - Purified mussel adhesive protein mefp-1 (Mytilus edulis foot protein 1) has been
      studied regarding its state of oligomerization and gross conformation in dilute
      solution. Sedimentation equilibrium in the analytical ultracentrifuge of a dilute
      solution of protein (0.4 mg/mL) in acetate buffer at pH 4.5 and I = 0.10 M
      yielded an apparent molecular weight (whole distribution weight average, Mw, app)
      of 114 000 +/- 5000 via the "M" procedure, a value in almost exact agreement with
      the monomeric molecular weight obtained by MALDI mass spectrometry. At this low
      concentration, it is reasonable to assume thermodynamic ideality, i.e., Mw,app
      approximately Mw. This result, together with plots of point weight average
      apparent molecular weight versus concentration for three different loading
      concentrations (0.4, 0.8, 1.0 mg/mL), clearly demonstrates that this protein is
      essentially monomeric in dilute solution. Sedimentation velocity experiments
      yielded an estimate of the sedimentation coefficient s020,w = 2.34 +/- 0.17 S,
      which for M = 110 000 gives a frictional ratio f/f0 = 3.2 +/- 0.3. The
      interpretation of this, in terms of an extended rather than globular conformation
      for the structure of mefp-1 in dilute solution, is considered, within plausible
      limits of molecular hydration, and models for the structure in solution are
      considered, in light of the thermodynamic nonideality behavior of these molecules
      and previously published circular dichroism data. The significance of these
      observations in terms of the bioadhesive properties of mefp-1 is described, and
      the very strong interaction in dilute solution with a mucin glycoprotein is
      demonstrated.

PMID- 9760247
TI  - The soluble granulocyte-macrophage colony-stimulating factor receptor's carboxyl
      terminal domain mediates retention of the soluble receptor on the cell surface
      through interaction with the granulocyte-macrophage colony-stimulating factor
      receptor beta-subunit.
AB  - The hematopoietic cytokine granulocyte-macrophage colony-stimulating factor (GM
      CSF) mediates its activity through binding to cell-surface receptors. The high
      affinity GM-CSF receptor (GMR) consists of two transmembrane-anchored subunits: a
      ligand-specific, low-affinity subunit (GMRalpha); and a signal-transducing beta
      subunit (GMRbeta). The human GMRalpha subunit also exists in a soluble isoform
      (SOLalpha) which antagonizes GM-CSF activity in vitro. Previous studies by us
      have shown that coexpression of SOLalpha and a mutated GMRbeta in BHK cells
      results in retention of SOLalpha on the cell surface and the formation of an
      intermediate affinity binding complex (Kd approximately 300 pM). This paper
      investigates the mechanism of the retention of SOLalpha on the cell surface. The
      data demonstrate that SOLalpha is anchored by a direct, ligand-independent
      interaction with GMRbeta which also occurs when SOLalpha is coexpressed with wild
      type GMRbeta. However, SOLalpha and wild-type GMRbeta form a complex which binds
      GM-CSF with high affinity (Kd = 39 pM), indistinguishable from the binding
      characteristics of the TMalpha/GMRbeta complex. The experiments further reveal
      that the interaction between SOLalpha and GMRbeta is abrogated by removal of the
      unique 16 amino acid carboxyl-terminal domain of SOLalpha. Specific mutation of
      cysteine 323 in this carboxyl-domain to alanine also eliminates the cell-surface
      retention of SOLalpha identifying this residue as being necessary for the
      formation of the SOLalpha/GMRbeta complex.

PMID- 9760248
TI  - Quantitative characterization of the binding of histamine by heparin.
AB  - Tissue histamine is stored in mast cell granules, presumably as a histamine
      heparin complex. Heparin is a polyelectrolyte, with a fraction of its anionic
      charge neutralized by condensed counterions. The interaction of heparin with
      histamine in aqueous solution was quantitatively characterized by 1H nuclear
      magnetic resonance (NMR) spectroscopy. Binding constants were determined from
      chemical shift-pH titration data for the C2H proton of the imidazolium ring for a
      wide range of histamine, heparin, and Na+ concentrations. The results indicate a
      binding stoichiometry of 1 histamine per heparin disaccharide repeat unit. The
      binding is electrostatic, as indicated by the strong dependence of the binding
      constant on Na+ concentration. From an analysis of the binding constants using
      the counterion condensation theory of polyelectrolytes, it was determined that
      the binding of H2A2+ results in displacement of 1.72 Na+ ions from the counterion
      condensation volume of heparin and that H2A2+ makes 2 ionic interactions with
      heparin. The displacement of Na+ from the counterion condensation volume of
      heparin by H2A2+ was also studied by 23Na NMR. From 23Na spin-lattice relaxation
      time data, it was determined directly that 1.78 Na+ ions are displaced per H2A2+
      bound by heparin. The results are discussed in terms of the ion exchange process
      which takes place when histamine is released by mast cells.

PMID- 9760249
TI  - Membrane penetration of cytosolic phospholipase A2 is necessary for its
      interfacial catalysis and arachidonate specificity.
AB  - To determine the mechanism of calcium-dependent membrane binding of cytosolic
      phospholipase A2 (cPLA2), we measured the interactions of cPLA2 with phospholipid
      monolayers and polymerizable mixed liposomes containing various phospholipids. In
      the presence of calcium, cPLA2 showed much higher penetrating power than
      secretory human pancreatic PLA2 toward anionic and electrically neutral
      phospholipid monolayers. cPLA2 also showed ca. 30-fold higher binding affinity
      for nonpolymerized 2, 3-bis[12-(lipoyloxy)dodecanoyl]-sn-glycero-1
      phosphoglycerol (D-BLPG) liposomes than for polymerized ones where the membrane
      penetration of protein is significantly restricted. Consistent with this
      difference in membrane binding affinity, cPLA2 showed 20-fold higher activity
      toward fluorogenic substrates, 1-O-(1-pyrenedecyl)-2-arachidonoyl-sn-glycero-3
      phosphocholine, inserted in nonpolymerized D-BLPG liposomes than the same
      substrate in polymerized D-BLPG liposomes. Furthermore, cPLA2 showed much higher
      sn-2 acyl group specificity (arachidonate specificity) and headgroup specificity
      in nonpolymerized D-BLPG liposomes than in polymerized D-BLPG liposomes. Finally,
      diacylglycerols, such as 1, 2-dioleoyl-sn-glycerol, selectively enhanced the
      membrane penetration, hydrophobic membrane binding, and interfacial enzyme
      activity of cPLA2. Taken together, these results indicate the following: (1)
      calcium not only brings cPLA2 to the membrane surface but also induces its
      membrane penetration. (2) This unique calcium-dependent membrane penetration of
      cPLA2 is necessary for its interfacial binding and substrate specificity. (3)
      Diacylglycerols might work as a cellular activator of cPLA2 by enhancing its
      membrane penetration and hydrophobic membrane binding.

PMID- 9760250
TI  - The influence of mutation at Glu44 and Glu56 of cytochrome b5 on the protein's
      stabilization and interaction between cytochrome c and cytochrome b5.
AB  - To characterize the roles played by Glu44 and Glu56 of cytochrome b5 in the
      formation of the electrostatic complex between cytochrome c and cytochrome b5,
      the Glu44, Glu56, or both sites were changed to alanine by site-directed
      mutagenesis. The influence of these two residues on the protein stability was
      probed by investigating the kinetic behaviors of protein denaturation in urea or
      upon heating and the heme-transfer reactions between apo-myoglobin and the
      variants of cytochrome b5. It has been found that when the Glu44 and/or Glu56 are
      mutated to alanine, the protein stability increases slightly due to the fact that
      the hydrophilic residue is changed to a hydrophobic one, resulting in the two
      pairs of helices surrounding the heme taking a more compact conformation. The
      difference in voltammetric behavior of cytochrome c, cytochrome b5, and its three
      mutants, Cyt b5 E44A, E56A, and E44/56A, alone and in 1:1 protein complexes
      demonstrates that both Glu44 and Glu56 of cytochrome b5 take part in the
      electrostatic interaction with cytochrome c. The entropy changes, DeltaS
      degreesrc and enthalpy changes, DeltaH degrees, derived from the temperature
      dependence of the formal reduction potentials of each protein in different
      protein systems suggest that, because of the mutual interaction with cytochrome
      c, cytochrome b5 mutants, especially the E44A-containing mutants, in the protein
      complexes suffer greater conformational changes upon reduction than that of the
      wild type. The variation of these thermodynamic parameters indicates that the
      strength of mutual interactions between cytochrome c and cytochrome b5 or its
      mutants has the following order: Cyt c/Cyt b5 > Cyt c/Cyt b5 E56A > Cyt c/Cyt b5
      E44A > Cyt c/Cyt b5 E44/56A.

PMID- 9760251
TI  - N-tosyl-L-phenylalanine chloromethyl ketone, a serine protease inhibitor,
      identifies glutamate 398 at the coenzyme-binding site of human aldehyde
      dehydrogenase. Evidence for a second "naked anion" at the active site.
AB  - Human aldehyde dehydrogenase isozymes were inactivated by N-tosyl-L-phenylalanine
      chloromethyl ketone (TPCK), an inhibitor of chymotrypsin. The inactivation was a
      first-order process that followed saturation kinetics. NAD and chloral when used
      together protected against inactivation. In steady-state kinetics, TPCK produced
      only slope effects versus varied NAD, both slope and intercept effects versus
      varied glycolaldehyde were produced, indicating that TPCK reacted with the same
      enzyme form with which NAD reacted. Ki values from steady-state kinetics and
      saturation kinetics were comparable. Use of [3H]-labeled TPCK showed that
      inactivation was associated with the incorporation of two molecules of TPCK per
      molecule of enzyme. The label incorporation occurred into a single tryptic
      peptide and also into a single chymotryptic peptide of the E1 isozyme.
      Purification of labeled peptides, followed by sequencing, demonstrated that E398
      of aldehyde dehydrogenase was labeled. Reaction of a haloketone, TPCK, with a
      carboxyl group of E398 indicates that E398 occurs as a "naked anion" within the
      molecule. This paper constitutes identification of the second (after E268) "naked
      anion" at the active site of aldehyde dehydrogenase.

PMID- 9760252
TI  - Kinetic studies on the removal of iron and aluminum from recombinant and site
      directed mutant N-lobe half transferrins.
AB  - Kinetic studies have been conducted in pH 7.4 Hepes buffer at 25 degreesC on the
      removal of Fe(III) and Al(III) from the recombinant N-lobe half molecule of human
      serum transferrin (Tf/2N) and from the R124A, K206A, and K296A mutants of this
      protein. The rates of iron removal from Tf/2N by 3-hydroxypyridin-4-one
      (deferiprone) and nitrilotriacetic acid (NTA) are essentially identical with
      previous results on N-terminal monoferric transferrin (Tf-FeN). For both Tf/2N
      and Tf-FeN, iron removal by deferiprone follows simple saturation kinetics, while
      iron removal by NTA follows simple first-order kinetics. There is some
      discrepancy between the two proteins with respect to iron removal by PPi, but
      this may be due to differences in the chloride concentrations among different
      studies. The addition of Fe(NTA)2 to R124A at ambient bicarbonate concentrations
      forms the Fe-NTA-Tf ternary complex, but the usual Fe-CO3-Tf complex can be
      formed by adding ferrous ion in the presence of a larger excess of bicarbonate.
      This complex releases its iron very rapidly by a mechanism that is first-order
      with respect to the ligand. This suggests that the first-order component of metal
      release from transferrin involves the displacement of the synergistic carbonate
      anion. Since iron removal from K206A and K296A at pH 7.4 is extremely slow,
      studies have been conducted on the more labile Al3+ complexes of Tf/2N, K206A,
      and K296A. The removal of Al3+ from Tf/2N by PPi follows the same complex kinetic
      order with respect to the ligand concentration that is observed for iron removal,
      while the removal of Al3+ from both K206A and K296A reverts to a simple
      saturation process. The addition of perchlorate retards the removal of Al3+ from
      both K206A and K296A, suggesting that these lysine residues are not associated
      with the allosteric effects of inorganic anions on the rates of metal removal.

PMID- 9760253
TI  - Oxidative modification of aldose reductase induced by copper ion. Factors and
      conditions affecting the process.
AB  - Bovine lens aldose reductase (ALR2) is inactivated by copper ion [Cu(II)] through
      an oxygen-independent oxidative modification process. A stoichiometry of 2 equiv
      of Cu(II)/enzyme mol is required to induce inactivation. While metal chelators
      such as EDTA or o-phenantroline prevent but do not reverse the ALR2 inactivation,
      DTT allows the enzyme activity to be rescued by inducing the recovery of the
      native enzyme form. The inactive enzyme form is characterized by the presence of
      2 equiv of bound copper, at least one of which present as Cu(I), and by the
      presence of two lesser equivalents, with respect to the native enzyme, of reduced
      thiol residues. Data are presented which indicate that the Cu-induced protein
      modification responsible for the inactivation of ALR2 is the generation on the
      enzyme of an intramolecular disulfide bond. GSH significantly interferes with the
      Cu-dependent inactivation of ALR2 and induces, through its oxidation to GSSG, the
      generation of an enzyme form linked to a glutathionyl residue by a disulfide
      bond.

PMID- 9760254
TI  - Novel function of the regulatory subunit of protein kinase A: regulation of
      cytochrome c oxidase activity and cytochrome c release.
AB  - There have been speculations that the regulatory (R) subunit of the cAMP
      dependent protein kinase (PKA) may have other functions. A recent study has shown
      that the catalytic (C) subunit of PKA may be regulated in a cAMP- and R subunit
      independent manner. However, evidence linking a function to the R subunit apart
      from inhibiting the C subunit has been elusive. In this report, interaction
      cloning experiments showed that the RIalpha subunit association with the
      cytochrome c oxidase subunit Vb (CoxVb) is cAMP-sensitive. Interaction was
      detected with a GST-RIalpha fusion protein as well as by coimmunoprecipitation.
      Transient treatment with cAMP-elevating agents inhibited cytochrome c oxidase in
      Chinese hamster ovary (CHO) cells with a concomitant decrease in cytochrome c
      levels in the mitochondria and an increase in its release into the cytosol.
      Furthermore, mutant cells harboring a defective RIalpha show increased cytochrome
      c oxidase activity and also constitutively lower levels of cytochrome c in
      comparison to either the wild-type cells or the C subunit mutant. These results
      suggest a novel mechanism of cAMP signaling through the interaction of RIalpha
      with CoxVb thereby regulating cytochrome c oxidase activity as well as the
      cytochrome c levels.

PMID- 9760255
TI  - Analysis of the TPA regulatory element in the genomic poly(ADP-ribose) synthetase
      gene in human leukemia U937 cells.
AB  - The human leukemia U937 cells differentiate into monocyte/macrophage-like cells
      when treated with 12-O-tetradecanoylphorbol-13-acetate (TPA). We observed that
      during this process, both protein and mRNA levels for PARS markedly decreased in
      U937 cells. Through deletion analysis of the PARS regulatory gene, we found that
      the sequence within the first intron region was responsible for the TPA-dependent
      repression. Electrophoretic mobility shift assays (EMSAs) and Southwestern blot
      analysis indicate that this element bound specifically to a nuclear protein. TPA
      treatment abolished the binding of the protein in U937 cells but not in HeLa
      cells. DNase I footprinting data show that the cis regulatory element is located
      between residues 328 and 383. We further examined the function of this cis
      element (BS207) in a basal promoter regulatory reporter construct and found that
      this cis element (BS207) functions as an enhancer via the binding of an unknown
      trans-acting factor. TPA treatment diminished the binding activity of the factor
      in U937 cells, resulting in a decrease in the enhanced activity to the basal
      level. These results suggest that abolishment of the binding of a special nuclear
      protein to the first intron of the PARS gene is related to the TPA-responsive
      downregulation of PARS in U937 cells.

PMID- 9760256
TI  - Implication of the tRNA initiation step for human immunodeficiency virus type 1
      reverse transcriptase in the mechanism of 3'-azido-3'-deoxythymidine (AZT)
      resistance.
AB  - There is a lack of correlation between biochemical studies and the observed
      clinical resistance of AIDS patients on long-term AZT therapy. Mutant HIV-1
      reverse transcriptase in the viral isolates from these patients shows a 100-fold
      decrease in sensitivity to AZT whereas little or no difference is observed in
      kinetic parameters in vitro using steady-state kinetic analysis. A pre-steady
      state kinetic analysis was used to examine the binding and incorporation of 2'
      deoxythymidine 5'-triphosphate (dTTP) and 3'-azido-3'-deoxythymidine 5'
      triphosphate (AZTTP) by wild-type HIV-1 reverse transcriptase and a clinically
      important AZT-resistant mutant form of the enzyme (D67N, K70R, T215Y, K219Q)
      utilizing a physiologically relevant RNA 18-mer/RNA 36-mer primer-template
      substrate. It was determined that with this RNA/RNA substrate there is a 2.6-fold
      increase in the selection for incorporation of the natural nucleotide dTTP over
      the unnatural nucleoside analogue AZTTP by AZT-resistant reverse transcriptase as
      compared to its wild-type form. This observation indicates that the tRNALys
      initiation step plays an important role in the development of drug resistance.
      Furthermore, this result implies that the structural basis of AZT resistance in
      HIV-1 reverse transcriptase involves the conformation of the RNA-DNA junction
      (formed upon attachment of a deoxynucleotide to the RNA primer). Taken together,
      these observations suggest a new pharmacological basis for the development of
      more effective and novel AIDS drugs.

PMID- 9760257
TI  - Structure and activity of the hairpin ribozyme in its natural junction
      conformation: effect of metal ions.
AB  - The natural form of the hairpin ribozyme consists of a four-way RNA junction of
      which the single-stranded loop-carrying helices are adjacent arms. The junction
      can be regarded as providing a framework for constructing the active ribozyme,
      and the rate of cleavage can be modulated by changing the conformation of the
      junction. We find that the junction-based form of the hairpin ribozyme is active
      in magnesium, calcium, or strontium ions, but not in manganese, cadmium, or
      sodium ions. Using fluorescence resonance energy transfer experiments, we have
      investigated the global structure of the ribozyme. The basic folding of the
      construct is based on pairwise helical stacking, so that the two loop-carrying
      arms are located on opposite stacked helical pairs. In the presence of magnesium,
      calcium, or strontium ions, the junction of the ribozyme undergoes a rotation
      into a distorted antiparallel geometry, creating close physical contact between
      the two loops. Manganese ions induce the same global folding, but no catalytic
      activity; this change in global conformation is therefore necessary but not
      sufficient for catalytic activity. Fitting the dependence of the conformation on
      ionic concentration to a two-state model suggests that cooperative binding of two
      ions is required to bring about the folding. However, further ion binding is
      required for cleavage activity. Cobalt hexammine ions also bring about global
      folding, while spermidine generates a more symmetrical form of the antiparallel
      structure. Cadmium ions generate a different folded form, interpreted in terms of
      close loop-loop association while the junction is unfolded. Sodium ions were
      unable to induce any folding of the ribozyme, which remained slightly parallel.
      These results are consistent with a folding process induced by the binding of two
      group IIA metal ions, distributed between the junction and the loop interface.

PMID- 9760258
TI  - Inhibitors of protein-RNA complexation that target the RNA: specific recognition
      of human immunodeficiency virus type 1 TAR RNA by small organic molecules.
AB  - TAR RNA represents an attractive target for the intervention of human
      immunodeficiency virus type 1 (HIV-1) replication by small molecules. We now
      describe three small molecule inhibitors of the HIV-1 Tat-TAR interaction that
      target the RNA, not the protein. The chemical structures and RNA binding
      characteristics of these inhibitors are unique for each molecule. Results from
      various biochemical and spectroscopic methods reveal that each of the three Tat
      TAR inhibitors recognizes a different structural feature at the bulge, lower
      stem, or loop region of TAR. Furthermore, one of these Tat-TAR inhibitors has
      been demonstrated, in cellular environments, to inhibit (a) a TAR-dependent, Tat
      activated transcription and (b) the replication of HIV-1 in a latently infectious
      model.

PMID- 9760259
TI  - Actinomycin D inhibition of DNA strand transfer reactions catalyzed by HIV-1
      reverse transcriptase and nucleocapsid protein.
AB  - Actinomycin D was found to be a potent inhibitor of HIV-1 reverse transcriptase
      catalyzed DNA strand transfer reactions. Using an oligonucleotide model system,
      actinomycin D inhibition of DNA strand transfer was examined to elucidate the
      mechanism of inhibition and further define the mechanism of DNA strand transfer.
      Our results show that actinomycin D inhibits HIV-1 reverse transcriptase
      catalyzed DNA strand transfer without inhibiting RNA-dependent or DNA-dependent
      DNA polymerase activity. Actinomycin D was found to strongly inhibit annealing of
      a primary DNA product to the DNA acceptor template, preventing the formation of a
      key reaction intermediate. The HIV-1 nucleocapsid protein has been shown to
      participate in catalytic events during reverse transcription including DNA strand
      transfer. Recombinant nucleocapsid protein was used in conjunction with
      actinomycin D in this model system to investigate how NC may participate in the
      mechanism of inhibition by actinomycin D and in DNA strand transfer. The
      inclusion of nucleocapsid protein was found to partially relieve both DNA
      annealing and strand transfer inhibition caused by actinomycin D. This study
      suggests a potential new mechanism for inhibiting retroviral replication by
      preventing the formation of replication intermediates.

PMID- 9760260
TI  - Ceruloplasmin copper induces oxidant damage by a redox process utilizing cell
      derived superoxide as reductant.
AB  - Oxidative damage by transition metals bound to proteins may be an important
      pathogenic mechanism. Ceruloplasmin (Cp) is a Cu-containing plasma protein
      thought to be involved in oxidative modification of lipoproteins. We have
      previously shown that Cp increased cell-mediated low-density lipoprotein (LDL)
      oxidation by a process requiring cell-derived superoxide, but the underlying
      chemical mechanism(s) is (are) unknown. We now show that superoxide reduction of
      Cp Cu is a critical reaction in cellular LDL oxidation. By bathocuproine
      disulfonate (BCS) binding and by superoxide utilization, we showed that exogenous
      superoxide reduces a single Cp Cu atom, the same Cu required for LDL oxidation.
      The Cu atom remained bound to Cp during the redox cycle. Three avenues of
      evidence showed that vascular cells reduce Cp Cu by a superoxide-dependent
      process. The 2-fold higher rate of Cp Cu reduction by smooth muscle cells (SMC)
      compared to endothelial cells (EC) was consistent with their relative rates of
      superoxide release. Furthermore, Cp Cu reduction by cells was blocked by Cu,Zn
      superoxide dismutase (SOD1). Finally, the level of superoxide produced by EC and
      SMC was sufficient to cause the amount of Cu reduction observed. An important
      role of Cp Cu reduction in LDL oxidation was suggested by results showing that
      SOD1 inhibited Cp Cu reduction and LDL oxidation by SMC with equal potency, while
      tumor necrosis factor-alpha stimulated both processes. In summary, these results
      show that superoxide is a critical cellular reductant of divalent transition
      metals involved in oxidation, and that protein-bound Cu is a substrate for this
      reaction. The role of these mechanisms in oxidative processes in vivo has yet to
      be defined.

PMID- 9760262
TI  - Proton transfer reactions linked to rhodopsin activation.
AB  - Purified bovine rhodopsin solubilized in dodecyl maltoside was photolyzed at 20
      degreesC with 477 nm light, and difference spectra were collected at time delays
      ranging from 10 micros to 10 ms after photolysis. Bromocresol purple was added to
      the samples to detect pH changes in the aqueous environment due to changes in the
      protonation state of rhodopsin. The data were analyzed using singular value
      decomposition and global exponential fitting, which revealed three exponential
      processes indicating the presence of at least four intermediates. Spectral
      changes of the indicator dye were separated from those of rhodopsin, and proton
      release and uptake rates were analyzed within the framework of rhodopsin
      photoreaction kinetics. Proton release occurred during Lumi decay to Meta-I380
      followed by uptake upon Meta-I380 decay and by a more significant proton uptake
      with the time course of Meta-I480 decay. On the basis of the estimated number of
      protons released and taken up in each step of the rhodopsin photoreaction, we
      concluded that two forms of Meta-II are present. The two forms of Meta-II, Meta
      IIa' and Meta-IIb, differ in protonation state from one another as do both from
      the earlier, 380 nm absorbing form, Meta-I380.

PMID- 9760261
TI  - The carboxyl-terminal tripeptide of the manganese-stabilizing protein is required
      for quantitative assembly into photosystem II and for high rates of oxygen
      evolution activity.
AB  - The extrinsic manganese stabilizing protein of photosystem II is required for Mn
      retention by the O2-evolving complex, accelerates the rate of O2 evolution, and
      protects photosytem II against photoinhibition. We report results from studies of
      the in vitro reconstitution of spinach photosytem II with recombinant manganese
      stabilizing protein with C-terminal deletions of two, three, and four amino
      acids. The deletions were the result of amber mutations introduced by site
      directed mutagenesis. Removal of the C-terminal dipeptide (Glu-Gln) did not
      diminish the ability of the manganese stabilizing protein either to rebind to or
      to restore high rates of O2 evolution to photosystem II preparations depleted of
      the native protein. Deletion of the C-terminal tripeptide (Leu-Glu-Gln) resulted
      in weakened but specific binding of manganese stabilizing protein to photosystem
      II and minimal recovery of O2 evolution activity. Removal of the C-terminal
      tetrapeptide (Gln-Leu-Glu-Gln) eliminated the ability of the subunit to interact
      stably with all of its available binding sites on photosystem II, as evidenced by
      the fact that this mutant was totally inactive in restoring O2 evolution
      activity. Evidence is presented to indicate that these mutational effects on the
      binding and function of the manganese stabilizing protein may be due to major
      changes in tertiary structure. The truncation mutations lacking either the C
      terminal tri- or tetrapeptide exhibit apparent size increases of 25 and 40%,
      respectively, when compared either to a mutant lacking the C-terminal dipeptide
      or to the wild-type protein.

PMID- 9760264
TI  - Kinetics of dimerization and interactions of p13suc1 with cyclin-dependent
      kinases.
AB  - The impact of p13suc1 on the conformation and regulation of cyclin-dependent
      kinases (cdks) and cyclins was investigated by spectroscopic and rapid kinetic
      approaches. In the absence of phosphorylation on cdks, p13suc1 formed stable
      complexes, mainly stabilized by hydrophobic interactions, specifically with cdk2
      and cdc2. The presence of cyclin A, associated with cdk2 or cdc2, increased the
      stability of the interaction between cdk2 and p13suc1 by a factor of 2. However,
      cyclin A did not modify the association rate of p13suc1 to cdk2, but the
      dissociation rate, which was decreased 3-fold. Moreover, binding of p13suc1 to
      cdk2 resulted in a 2-fold decrease in the release of nucleotide from cdk2,
      indicating that p13suc1 induces a marked change in the structure of the
      nucleotide binding site of cdks. On the basis of the structure of cdk2/CksHs1
      complex and on our kinetic results, we propose that the binding of Cks proteins
      to C-lobe of cdk2 is stabilized by the presence of cyclin A and that it may
      modify the orientation of the loop carrying residues 14 and 15 and their
      consequent access for dephosphorylation by cdc25 phosphatases. Finally, we have
      shown that dimerization of p13suc1 in the presence of zinc abolishes its
      interaction with cdks, which suggests that the binding of p13suc1 to cdk2 or
      cdk2/cyclin A may be regulated by dimerization of p13suc1 in vivo.

PMID- 9760263
TI  - Involvement of histidine 190 on the D1 protein in electron/proton transfer
      reactions on the donor side of photosystem II.
AB  - Flash-induced chlorophyll fluorescence kinetics from photosystem II in thylakoids
      from the dark-grown wild type and two site-directed mutants of the D1 protein
      His190 residue (D1-H190) in Chlamydomonas reinhardtii have been characterized.
      Induction of the chlorophyll fluorescence on the first flash, reflecting electron
      transport from YZ to P680(+), exhibited a strong pH dependence with a pK of 7.6
      in the dark-grown wild type which lacks the Mn cluster. The chlorophyll
      fluorescence decay, measured in the presence of DCMU, which reflects
      recombination between QA- and YZox, was also pH-dependent with a similar pK of
      7.5. These results indicate participation by the same base, which is suggested to
      be D1-H190, in oxidation and reduction of YZ in forward electron transfer and
      recombination pathways, respectively. This hypothesis was tested in the D1-H190
      mutants. Induction of chlorophyll fluorescence in these H190 mutants has been
      observed to be inefficient due to slow electron transfer from YZ to P680(+)
      [Roffey, R. A., et al. (1994) Biochim. Biophys. Acta 1185, 257-270]. We show that
      this reaction is pH-dependent, with a pK of 8. 1, and at pH >/=9, the
      fluorescence induction is efficient in the H190 mutants, suggesting direct
      titration of YZ. The efficient oxidation of YZ ( approximately 70% at pH 9.0) at
      high pH was confirmed by kinetic EPR measurements. In contrast to the wild type,
      the H190 mutants show little or no observable fluorescence decay. Our data
      suggest that H190 is an essential component in the electron transfer reactions in
      photosystem II and acts as a proton acceptor upon YZ oxidation. In the H190
      mutants, this reaction is inefficient and YZ oxidation only occurs at elevated
      pHs when YZ itself probably is deprotonated. We also propose that H190 is able to
      return a proton to YZox during electron recombination from QA- in a reaction
      which does not take place in the D1-H190 mutants.

PMID- 9760265
TI  - A Raman spectroscopic characterization of bonding in the complex of horse liver
      alcohol dehydrogenase with NADH and N-cyclohexylformamide.
AB  - The binding of N-cyclohexylformamide (CXF) to the complex of horse liver alcohol
      dehydrogenase with NADH mimics that of the Michaelis complex for aldehyde
      reduction catalyzed by the enzyme. The Raman spectra of bound CXF and its 13C-
      and 15N-substituted derivatives have been obtained using Raman difference
      techniques, and the results are compared with CXF spectra in aqueous solution and
      in methylene chloride. The results indicate that the amide N-H bond is trans to
      the C=O bond of CXF both in solution and in the enzyme ternary complex. The C=O
      stretch and N-H bending modes of the amide of CXF shift -16 and -9 cm-1,
      respectively, in the enzyme ternary complex relative to that in aqueous solution
      and -48 and 36 cm-1, respectively, relative to that in methylene chloride. Ab
      initio normal mode calculations on various model systems of CXF show that the
      observed frequency changes of the C=O stretch mode have contributions from the
      frequency changes induced by the environmental changes near both the local C=O
      bond and the remote N-H bond. The same is true for the observed N-H bending
      frequency change. Our calculations also show that the environmentally induced
      frequency changes are additive so that it is possible to determine the C=O
      stretch (or N-H bending) frequency change that is due to the local interaction
      change near the C=O (or N-H) bond from the observed frequency changes. On the
      basis of these results and the empirical relationship between the C=O stretch
      frequency shift and the interaction enthalpy change on the C=O bond developed
      here, it is found that the C=O group of CXF in the enzyme/NADH/CXF complex binds
      with a favorable interaction enthalpy of approximately 5.5 kcal/mol relative to
      water. Similar analysis suggests that the N-H moiety of CXF is destabilized in
      the ternary complex by about 1.5 kcal/mol relative to water but is stabilized by
      about 1.5 kcal/mol relative to a hydrophobic environment. The analysis describes
      quantitatively the binding of the C=O of CXF with the catalytic zinc and the
      hydroxyl group of Ser-48 and the interaction of the N-H with the benzene ring of
      Phe-93 of the enzyme.

PMID- 9760266
TI  - Environment- and sequence-dependent modulation of the double-stranded to single
      stranded conformational transition of gramicidin A in membranes.
AB  - The role of the membrane lipid composition and the individual Trp residues in the
      conformational rearrangement of gramicidin A along the folding pathway to its
      channel conformation has been examined in phospholipid bilayers by means of
      previously described size-exclusion high-performance liquid chromatography HPLC
      based strategy (Bano et al. (1991) Biochemistry 30, 886). It has been
      demonstrated that the chemical composition of the membrane influences the
      transition rate of the peptide rearrangement from double-stranded dimers to beta
      helical monomers. The chemical modification of Trp residues, or its substitution
      by the more hydrophobic residues phenylalanine or naphthylalanine, stabilized the
      double-stranded dimer conformation in model membranes. This effect was more
      notable as the number of Trp-substituted residues increased (tetra > tri > di >
      mono), and it was also influenced by the specific position of the substituted
      amino acid residue in the sequence, in the order Trp-9 approximately Trp-13 > Trp
      11 > Trp-15. Moreover, it was verified that nearly a full contingent of indoles
      (Trp-13, -11, and -9) is necessary to induce a quantitative conversion from
      double-stranded dimers to single-stranded monomers, although Trp-9 and Trp-13
      seemed to be key residues for the stabilization of the beta-helical monomeric
      conformation of gramicidin A. The conformation adopted for monomeric Trp --> Phe
      substitution analogues in lipid vesicles resulted in CD spectra similar to the
      typical single-stranded beta6.3-helical conformation of gramicidin A. However,
      the Trp --> Phe substitution analogues showed decreased antibiotic activity as
      the number of Trp decreased.

PMID- 9760268
TI  - The helix-coil transition of DNA duplexes and hairpins observed by multiple
      fluorescence parameters.
AB  - The thermal denaturation of 8-20-bp DNA duplexes labeled with fluorescein and
      tetramethylrhodamine at opposing 5'-ends was investigated by monitoring the
      fluorescence intensity of the dyes, the fluorescence anisotropy of
      tetramethylrhodamine, the fluorescence resonance energy transfer between
      fluorescein and rhodamine, and, for the 20-bp duplex, the UV absorption. Melting
      experiments with the single strands of the duplexes revealed that the single
      strands can form hairpins stabilized by only a few base pairs. The thermal
      denaturation curves of the duplexes were fitted well to an extended all-or-none
      model assuming that only the fully base-paired duplex, the maximally base-paired
      hairpin, and the random coil conformations are present simultaneously. The extent
      of-melting versus temperature curves derived from the different spectroscopic
      parameters are nearly identical, provided that the analysis of the baselines is
      carried out correctly; the DeltaH and DeltaS of the dissociation compare well
      with predictions based on nearest neighbor interaction values available in the
      literature. Our results imply that for all the oligonucleotides other than the 34
      bp oligomer, no partially melted intermediates other than hairpins are present in
      the reaction mixture in amounts that can be detected by our methods. The melting
      of the hairpins was also studied directly using single-stranded oligonucleotides.
      The melting of a 34-bp duplex can be accounted for by a statistical zipper model.

PMID- 9760267
TI  - Transient kinetic studies on the interaction of Ras and the Ras-binding domain of
      c-Raf-1 reveal rapid equilibration of the complex.
AB  - Transient kinetic methods have been used to analyze the interaction between the
      Ras-binding domain (RBD) of c-Raf-1 and a complex of H-Ras and a GTP analogue.
      The results obtained show that the binding is a two-step process, with an initial
      rapid equilibrium step being followed by an isomerization reaction occurring at
      several hundred per second. The reversal of this step determines the rate
      constant for dissociation, which is on the order of 10 s-1. The lifetime of the
      complex is therefore on the order of 50-100 ms, which is much shorter than the
      lifetime of GTP at the active site of H-Ras as determined by the intrinsic GTPase
      reaction. This suggests that multiple interactions of a single activated Ras
      molecule and Raf can occur, the number being limited by the competing interaction
      with GAP. The GDP complex of H-Ras binds more than 2 orders of magnitude more
      weakly than the GTP-analogue complex, mainly due to a significant weakening of
      the initial binding equilibrium reaction in the GDP state, thereby avoiding even
      short-lived recruitment of Raf to the plasma membrane by the inactive Ras form.

PMID- 9760269
TI  - Human cruciform binding protein belongs to the 14-3-3 family.
AB  - Cruciform DNA has been implicated in the initiation of DNA replication. Recently,
      we identified and purified from human (HeLa) cells a protein, CBP, with binding
      specificity for cruciform DNA. We have reported previously that the CBP activity
      sediments at approximately 66 kDa in a glycerol gradient. Here, photochemical
      cross-linking studies and Southwestern analyses confirm that a 70 kDa polypeptide
      interacts specifically with cruciform DNA. Microsequence analysis of tryptic
      peptides of the 70 kDa CBP reveals that it is 100% homologous to the 14-3-3
      family of proteins and shows that CBP contains the epsilon, beta, gamma, and zeta
      isoforms of the 14-3-3 family. In addition to polypeptides with the
      characteristic molecular mass of 14-3-3 proteins (30 and 33 kDa), CBP also
      contains a polypeptide of 35 kDa which is recognized by an antibody specific for
      the epsilon isoform of 14-3-3. Cruciform-specific binding activity is also
      detected in 14-3-3 proteins purified from sheep brain. Immunofluorescene studies
      confirm the presence of the epsilon, beta, and zeta isoforms of 14-3-3 proteins
      in the nuclei of HeLa cells. The 14-3-3 family of proteins has been implicated in
      cell cycle control, and members of this family have been shown to interact with
      various signaling proteins. Cruciform binding is a new activity associated with
      the 14-3-3 family.

PMID- 9760270
TI  - Binding and reactivity of Candida albicans estrogen binding protein with steroid
      and other substrates.
AB  - In this report recombinant estrogen binding protein (EBP1), isolated originally
      from Candida albicans as a result of its high affinity for 17beta-estradiol, has
      been purified extensively using a modified affinity purification scheme
      originally developed for a homolog of EBP1, old yellow enzyme (OYE). It is shown
      that like OYE, the protein binds a variety of compounds with a phenolic
      structure, including 17beta-estradiol, and compounds with an alpha, beta
      unsaturated keto or aldehyde structure. In addition, EBP1 exhibits an NADPH
      oxidoreductase activity, transferring electrons from NADPH to all alpha,beta
      unsaturated ketones and aldehydes tested via the tightly bound FMN cofactor.
      Analysis of the steady-state kinetics of these reactions indicate a tetra uni
      ping-pong mechanism. Inhibition of the steady-state reaction by 17beta-estradiol
      gives a Ki = 10 +/- 2 nM, and indicates exclusive binding of this steroid to the
      enzyme in its oxidized state. In contrast, 19-nortestosterone binds to both
      oxidized and reduced forms of the enzyme with dissociation constants of 600 +/-
      100 and 650 +/- 90 nM, respectively. EBP1 also catalyzes a disproportionation
      reaction with certain compounds, in which two molecules of a cylic alpha,beta
      unsaturated ketone, including the steroid 19-nortestosterone, are individually
      aromatized and reduced to the corresponding saturated ketone. Despite the
      extensive similarity in sequence and enzymic activity, notable differences
      between EBP1 and the OYE family of proteins exist with regard to the binding
      behavior and reactivity with the two steroids tested here, estradiol and 19
      nortestosterone.

PMID- 9760271
TI  - Role of drug disposition in drug hypersensitivity: a chemical, molecular, and
      clinical perspective.

PMID- 9760272
TI  - Formation of a fluorescent adduct in the reaction of 2'-deoxyadenosine with a
      malonaldehyde-acetaldehyde condensation product.
AB  - Malonaldehyde (malondialdehyde, MDA) was reacted with 2'-deoxyadenosine in
      buffered aqueous solution. HPLC analyses of the reaction mixtures showed that,
      besides the two previously characterized N6-propenal (M1dA) and N6-oxazocinyl
      (M3dA) adenine adducts, a third compound eluting at longer retention time was
      formed. The compound generated a strong peak in the chromatogram recorded by a
      fluorescence detector. The new compound was isolated by preparative C18
      chromatography, and its structure was characterized by UV absorbance,
      fluorescence emission, 1H and 13C NMR spectroscopy, and mass spectrometry. The
      product was identified as 9-(2'-deoxyribosyl)-6-(3,5-diformyl-4-methyl-1, 4
      dihydro-1-pyridyl)purine (M2AA-dA). The yield of the product was 0.8% following 7
      days of reaction at 37 degreesC and pH 4.6. Lower yields were obtained at higher
      pH conditions. By the addition of acetaldehyde, the yield increased about 10-fold
      at all studied pH conditions. The adduct was most likely formed by an initial
      condensation of two molecules of malonaldehyde with one molecule of acetaldehyde
      followed by reaction of the condensation product with the exocyclic amino group
      of 2'-deoxyadenosine. The identification of this adduct shows that acetaldehyde
      may react with DNA bases also through an initially formed malonaldehyde
      acetaldehyde condensation product.

PMID- 9760273
TI  - Generation of antibodies to Di- and trichloroacetylated proteins and
      immunochemical detection of protein adducts in rats treated with perchloroethene.
AB  - Antibodies directed against chemical specific protein modifications are valuable
      tools to detect and comparatively quantify protein modifications. Both Nepsilon
      (dichloroacetyl)-L-lysine and Nepsilon-(trichloroacety)l-L-lysine have been
      detected as modified amino acids in liver and kidneys of rats treated with
      perchloroethene (PER) after proteolysis. These protein modifications are formed
      by the interaction of reactive metabolites formed from PER with proteins. In this
      study we developed monospecific antibodies to dichloroacetylated and to
      trichloroacetylated amino acids to detect modified proteins in the target organs
      of PER toxicity. These antibodies were prepared by immunization of rabbits with
      modified keyhole limpet hemocyanin (KLH) coupled with either the dichloroacetyl
      or trichloroacetyl moiety. Enzyme-linked immunosorbent assays (ELISA) indicated
      that the polyclonal rabbit sera recognized dichloroacetylated or
      trichloroacetylated rabbit serum albumin (RSA), but not unmodified protein.
      Therefore, we further purified rabbit antisera on either Nepsilon
      (dichloroacetyl)-L-lysine or Nepsilon-(trichloroacetyl)-L-lysine immobilized to
      immunoaffinity columns to obtain monospecific antibodies. The potential of these
      antibodies in the detection of di- and trichloroacetylated proteins and their
      selectivity for the desired dichloroacetyl or trichloroacetyl group was
      demonstrated in competitive enzme-linked immunosorbent assays with several
      structurally related compounds. Anti-dichloroacetyl (anti-DCA) antibody binding
      to dichloroacetylated RSA was inhibited by Nepsilon-(dichloroacetyl)-L-lysine
      with an IC50 value of 150 microM whereas inhibition by Nepsilon
      (monochloroacetyl)-L-lysine and Nepsilon-(trichloroacetyl)-L-lysine showed an
      IC50 value of 100 mM. The binding of the anti-trichloroacetyl (anti-TCA) antibody
      to trichloroacetylated RSA was inhibited by Nepsilon-(dichloroacetyl)-L-lysine
      with an IC50 value of 80 mM. The inhibition by Nepsilon-(trichloroacetyl)-L
      lysine was again 3 orders of magnitude stronger resulting in an IC50 value of 90
      microM. Nepsilon-(acetyl)-L-lysine and unmodified RSA did not effect antibody
      binding to the chemically modified antigen. The antibodies were also successfully
      applied to detect modified proteins in subcellular fractions of liver and kidney
      from PER treated rats demonstrated in immunoblot. Protein adduct formation from
      different PER metabolism pathways was confirmed by the observation that the
      majority of dichloroacetylated proteins were located in kidney mitochondria and
      trichloroacetylated proteins were located in liver microsomes.

PMID- 9760274
TI  - A novel vicinal lesion obtained from the oxidative photosensitization of TpdG:
      characterization and mechanistic aspects.
AB  - A new type of vicinal base lesion was isolated from the photosensitization of
      TpdG in aerated aqueous solution. One- and two-dimensional NMR measurements were
      used together with mass spectrometry to accurately characterize the new adduct.
      Chemical detection of guanidine provided additional structural information on the
      base moiety at the 3'-OH terminal end. Altogether the experiments results were
      indicative of the occurrence of a covalent bonding between the pyrimidine ring on
      the 5'-OH terminal end and the imidazole ring on the 3'-OH terminal end through a
      methylene bridge. Photosensitization studies of TpdG, thymidine, and 2'
      deoxyguanosine in the presence of either benzophenone, menadione, or riboflavin
      associated with isotopic labeling experiments using enriched oxygen and water
      provided relevant information on the mechanism of formation of the adduct. The
      results of these experiments clearly demonstrated that the initial event leading
      to the formation of the lesion is the abstraction of a hydrogen atom from the
      methyl group of the thymine base moiety of TpdG. This is followed by the addition
      of the methyl-centered radical to the C-4 atom of the guanine ring which gives
      rise to the vicinal lesion after reaction with molecular oxygen and subsequent
      rearrangement.

PMID- 9760275
TI  - Interactions of Nickel(II) with histones: interactions of Nickel(II) with CH3CO
      Thr-Glu-Ser-His-His-Lys-NH2, a peptide modeling the potential metal binding site
      in the "C-Tail" region of histone H2A.
AB  - A combined pH-metric and spectroscopic (UV/vis, CD, NMR) study of the Ni(II)
      binding to CH3CO-Thr-Glu-Ser-His-His-Lys-NH2 (AcTESHHKam), a blocked hexapeptide
      modeling a part of the C-terminal sequence of the major variant of histone H2A
      (residues 120-125), revealed the formation of a pseudo-octahedral NiHL complex in
      weakly acidic and neutral solutions. Ni(II) is bound to the peptide through
      imidazole nitrogens on both of its histidine residues and the carboxylate of the
      side chain of glutamic acid. At higher pH, a series of square-planar complexes
      are formed. This process is accompanied by hydrolytic degradation of the peptide.
      At pH 7.4, the peptide hydrolyzes in a Ni(II)-assisted fashion, yielding the
      square-planar Ni(II) complex of SHHKam as the sole product detected by CD, MALDI
      TOF MS, and HPLC. Quantitative analysis of complex stabilities indicates that the
      -TESHHK- motif is a very likely binding site for carcinogenic Ni(II) ions in the
      cell nucleus. The Ni(II)-assisted hydrolysis of the C-terminal chain of histone
      H2A may provide a novel mechanism of genotoxicity combining the damage to the
      nucleosome with the generation of further toxic Ni(II) species.

PMID- 9760276
TI  - Activation of human polymorphonuclear leukocytes by products derived from the
      peroxidation of human red blood cell membranes.
AB  - Oxidation of red blood cell (RBC) ghost preparations initiated by tert-butyl
      hydroperoxide (tBuOOH) was employed to explore the formation of lipid products
      derived from endogenous phospholipids that specifically expressed biological
      activity toward the human polymorphonuclear leukocyte (PMN). Common measure of
      lipid peroxidation, thiobarbituric acid-reactive substances (TBARS) and the
      increased absorbance at 235 nm consistent with the formation of conjugated
      dienes, was observed following a 90-min incubation of RBC ghosts with tBuOOH.
      Saponification of phospholipids and separation of the resultant fatty acids by RP
      HPLC permitted direct mass spectrometric analysis of oxidized fatty acids.
      Individual HPLC fractions were assayed for their ability to increase
      intracellular free calcium ion concentrations in human PMN to guide structural
      investigations. Two fractions were found to contain biologically active
      components, and tandem mass spectrometric analysis of the abundant ions observed
      in these fractions resulted in the characterization of several oxidized
      polyunsaturated fatty acids derived from arachidonic and linoleic acids. The
      major components in these fractions included 5-hydroxyeicosatetraenoic acid (5
      HETE) and 5-hydroperoxyeicosatetraenoic acid (5-HpETE). The dose-dependent
      increases in intracellular calcium in the neutrophil using synthetic 5(rac)-HETE,
      5(rac)-HpETE, and 5-oxo-ETE were found to have EC50's of 250, 6, and 3 nM,
      respectively. The quantity of 5-oxygenated arachidonate components present in
      oxidized RBC was consistent with the observed biological response elicited by
      fractions A and B. This study suggests that 5-HETE and 5-HpETE are abundant
      products of lipid peroxidation of cellular membranes and that these racemic
      products possess significant biological activity. Such compounds could play
      important roles as mediators of the cellular response to toxicologic stimuli that
      generate free radical species.

PMID- 9760277
TI  - An improved 32P-postlabeling/high-performance liquid chromatography method for
      the analysis of the malondialdehye-derived 1, N2-propanodeoxyguanosine DNA adduct
      in animal and human tissues.
AB  - Malondialdehyde (MDA) is a major lipid peroxidation product that is mutagenic and
      tumorigenic. The MDA-modified DNA adduct, 3-(2-deoxy-beta-D-erythro
      pentofuranosyl)pyrimido[1, 2-alpha]purin-10(3H)-one (M1G), has been detected in
      human tissues and may be a marker of human cancer risk. In this paper, we
      describe an improved 32P-postlabeling/HPLC method for sensitive detection and
      quantitation of this MDA-modified 2'-deoxyribonucleotide adduct. Specific
      improvements include (i) unequivocal structural identification of the
      postlabeling products, both the 3', 5'-bisphosphate of M1G (MDA-3',5'-dGDP) and
      the 5'-monophosphate of M1G (MDA-5'-dGMP); (ii) efficient separation of the 32P
      postlabeling products by HPLC; and (iii) the incorporation of a synthetically
      prepared MDA-modified DNA (or the 3'-monophosphate of M1G) with a known
      modification level as an internal standard. This improved quantitative
      methodology provides high intra- and inter-assay reproducibility and has been
      applied to the analysis of this adduct in rodent and human samples.

PMID- 9760278
TI  - Formation of 1,N6-etheno-2'-deoxyadenosine adducts by trans,trans-2, 4
      Decadienal.
AB  - trans,trans-2,4-Decadienal (DDE) is an important breakdown product of lipid
      peroxidation. This aldehyde is cytotoxic to mammalian cells and is known to be
      implicated in DNA damage. Therefore, attempts were made in this work to assess
      the reactivity of DDE with 2'-deoxyadenosine (dAdo). It was shown that DDE is
      able to bind to 2'-deoxyadenosine, yielding highly fluorescent products. Besides
      1, N6-etheno-2'-deoxyadenosine (epsilondAdo), two other related adducts, 1-[3-(2
      deoxy-beta-D-erythro-pentofuranosyl)-3H-imidazo[2, 1-i]purin-7-yl]-1,2,3
      octanetriol and 1-[3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3H-imidazo[2, 1
      i]purin-7-yl]-1,2-heptanediol, were isolated by reverse phase high-performance
      liquid chromatography and characterized on the basis of their UV, fluorescence,
      nuclear magnetic resonance, and mass spectrometry features. The reaction
      mechanism for the formation of the DDE-2'-deoxyadenosine adducts involves 2,4
      decadienal epoxidation and subsequent addition to the N2 amino group of 2'
      deoxyadenosine, followed by cyclization at the N-1 site. Adducts differ by the
      length of carbon side chain and the number of hydroxyl groups. The present data
      indicate that DDE can be epoxidized by peroxides, and the resulting products are
      able to form several adducts with 2'-deoxyadenosine and/or DNA. Endogenous DNA
      adduct formation can contribute to the already reported high cytotoxicity of DDE
      to mammalian cells.

PMID- 9760279
TI  - Selectivity of polycyclic inhibitors for human cytochrome P450s 1A1, 1A2, and
      1B1.
AB  - Human cytochrome P450s 1A1, 1A2, and 1B1 are known to have overlapping substrate
      specificities. All are regulated in part by the Ah locus; P450 1A2 is expressed
      essentially only in liver, but P450s 1A1 and 1B1 are both expressed in many
      extrahepatic tissues. Twenty-five polycyclic hydrocarbons, many containing
      acetylenic side chains, were examined as inhibitors of the three enzymes using 7
      ethoxyresorufin O-deethylation as the enzyme assay in all cases. Several
      compounds were inhibitory at low nanomolar concentrations. 1-(1-Propynyl)pyrene
      and 2-(1-propynyl)phenanthrene nearly completely inhibited P450 1A1 at
      concentrations at which no P450 1B1 inhibition was observed. 2-Ethynylpyrene and
      alpha-naphthoflavone (7, 8-benzoflavone) nearly completely inhibited P450 1B1 at
      concentrations at which no P450 1A1 inhibition was noted. All four of the above
      compounds also inhibited P450 1A2. Several polycyclic hydrocarbons devoid of
      acetylenic groups were also inhibitory with respect to all three P450s. Some of
      the acetylenic compounds examined showed enhanced inhibition following
      preincubation with the P450s in the presence of cofactors NADPH and O2. However,
      of seven compounds (five acetylenes) tested with P450 1B1, only two [2
      ethynylpyrene and 4-(1-propynyl)biphenyl] showed such evidence for mechanism
      based inactivation. We conclude that (i) several polycyclic hydrocarbons and
      their oxidation products are very inhibitory with respect to human P450s 1A1,
      1A2, and 1B1; (ii) of these inhibitors only some are mechanism-based
      inactivators; and (iii) some of the inhibitors are potentially useful for
      distinguishing between human P450s 1A1 and 1B1.

PMID- 9760280
TI  - Synthesis and characterization of bay region halohydrins derived from
      Benzo[a]pyrene diol epoxide and their role as intermediates in halide-catalyzed
      cis adduct formation.
AB  - The bay region epoxide of benzo[a]pyrene (anti-BPDE) alkylates DNA to form
      adducts with >98% trans stereochemistry. Halide ions catalyze this reaction;
      however, this pathway is characterized by the formation of adducts with altered
      cis stereochemistry. Bay region halohydrins are possible intermediates in these
      reactions, but are too unstable to be isolated from aqueous solutions. However,
      we successfully synthesized halohydrins in tetrahydrofuran (THF) by treatment of
      anti-BPDE with the corresponding lithium halide salt in the presence of acetic
      acid. Absorbance and CD spectroscopy clearly indicated the formation of chloro-,
      bromo-, and iodohydrins. The structure and stereochemistry of the chlorohydrin
      was established by NMR. Chloride addition is exclusively at the benzylic position
      of the epoxide, and the stereochemistry of the C-9 and -10 positions is trans.
      The long-wavelength absorbance band in the chloro-, bromo-, and iodohydrin is red
      shifted 7, 13, and 22 nm, respectively, relative to the hydrolysis product of
      anti-BPDE. The ellipticity of the same absorbance band in CD spectra of
      enantiomerically pure halohydrins is opposite in sign compared to that of the
      corresponding anti-BPDE enantiomer. The relative stability of these derivatives
      is chlorohydrin > bromohydrin > iodohydrin. The chloro- and bromohydrins were
      isolated, but the iodohydrin decomposed during this manipulation. The addition of
      500 mM chloride decreased the hydrolysis rate of the chlorohydrin 4-fold in 50%
      THF/buffer. Direct evidence for the transient formation of the iodohydrin in
      aqueous buffer/acetone mixtures was obtained by absorbance spectroscopy. At 1 M
      chloride, bromide, and iodide, alkylation of deoxyadenosine by anti-BPDE in
      aqueous buffer yields 85, 91, and 92% cis adducts, respectively. In the absence
      of halide, alkylation of deoxyadenosine in buffer by anti-BPDE, the chlorohydrin,
      and the bromohydrin yields 32, 65, and 83% cis adducts, respectively.

PMID- 9760281
TI  - Peroxynitrite-mediated nitration of tyrosine and inactivation of the catalytic
      activity of cytochrome P450 2B1.
AB  - The addition of peroxynitrite to purified cytochrome P450 2B1 resulted in a
      concentration-dependent loss of the NADPH- and reductase-supported or tert
      butylhydroperoxide-supported 7-ethoxy-4-(trifluoromethyl)coumarin O-deethylation
      activity of P450 2B1 with IC50 values of 39 and 210 microM, respectively. After
      incubation of P450 2B1 with 300 microM peroxynitrite, the heme moiety was not
      altered, but the apoprotein was modified as shown by HPLC and spectral analysis.
      Western blot analysis of peroxynitrite-treated P450 2B1 demonstrated the presence
      of an extensive immunoreactivite band after incubating with anti-nitrotyrosine
      antibody. However, the immunostaining was completely abolished after coincubation
      of the anti-nitrotyrosine antibody with 10 mM nitrotyrosine. These results
      indicated that one or more of the tyrosine residues in P450 2B1 were modified to
      nitrotyrosines. The decrease in the enzymatic activity correlated with the
      increase in the extent of tyrosine nitration. Further demonstration of tyrosine
      nitration was confirmed by GC/MS analysis by using 13C-labeled tyrosine and
      nitrotyrosine as internal standards; approximately 0.97 mol of nitrotyrosine per
      mole of P450 2B1 was found after treatment with peroxynitrite. The peroxynitrite
      treated P450 2B1 was digested with Lys C, and the resulting peptides were
      separated by Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE). The amino acid sequence of the major nitrotyrosine-containing peptide
      corresponded to a peptide containing amino acid residues 160-225 of P450 2B1,
      which contains two tyrosine residues. Thus, incubation of P450 2B1 with
      peroxynitrite resulted in the nitration of tyrosines at either residue 190 or 203
      or at both residues of P450 2B1 concomitant with a loss of 2B1-dependent
      activity.

PMID- 9760282
TI  - In vitro inhibition of thyroid hormone sulfation by hydroxylated metabolites of
      halogenated aromatic hydrocarbons.
AB  - Earlier studies in our laboratory showed that hydroxylated metabolites of
      polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), and dibenzofurans
      (PCDFs) competitively inhibit thyroxine (T4) binding to transthyretin (TTR) and
      type I deiodinase (D1) activity. In this study, we investigated the possible
      inhibitory effects of hydroxylated metabolites of polyhalogenated aromatic
      hydrocarbons (PHAHs) on iodothyronine sulfotransferase activity. Rat liver
      cytosol was used as a source of sulfotransferase enzyme in an in vitro assay with
      125I-labeled 3,3'-diiodothyronine (T2) as a model substrate. Increasing amounts
      of hydroxylated PCBs, PCDDs, or PCDFs or extracts from incubation mixtures of
      PHAHs and induced liver microsomes were added as potential inhibitors of T2
      sulfotransferase activity. Hydroxylated metabolites of PCBs, PCDDs, and PCDFs
      were found to be potent inhibitors of T2 sulfotransferase activity in vitro with
      IC50 values in the low micromolar range (0.2-3.8 microM). The most potent
      inhibitor of T2 sulfotransferase activity in our experiments was the PCB
      metabolite 3-hydroxy-2,3',4, 4',5-pentachlorobiphenyl with an IC50 value of 0.2
      microM. A hydroxyl group in the para or meta position appeared to be an important
      structural requirement for T2 sulfotransferase inhibition by PCB metabolites.
      Ortho hydroxy PCBs were much less potent, and none of the parent PHAHs was
      capable of inhibiting T2 sulfotransferase activity. In addition, the formation of
      T2 sulfotransferase-inhibiting metabolites of individual brominated diphenyl
      ethers and nitrofen as well as from some commercial PHAH mixtures (e.g., Bromkal,
      Clophen A50, and Aroclor 1254) was also demonstrated. These results indicate that
      hydroxylated PHAHs are potent inhibitors of thyroid hormone sulfation. Since
      thyroid hormone sulfation may play an important role in regulating free hormone
      levels in the fetus, and PCB metabolites are known to accumulate in fetal tissues
      after maternal exposure to PCBs, these observations may have implications for
      fetal thyroid hormone homeostasis and development.

PMID- 9760283
TI  - Chlorothioketene, the ultimate reactive intermediate formed by cysteine conjugate
      beta-lyase-mediated cleavage of the trichloroethene metabolite S-(1,2
      Dichlorovinyl)-L-cysteine, forms cytosine adducts in organic solvents, but not in
      aqueous solution.
AB  - Chlorothioketene has been suggested as a reactive intermediate formed by the
      cysteine conjugate beta-lyase-mediated cleavage of S-(1,2-dichlorovinyl)-L
      cysteine, a minor metabolite of trichloroethene. Halothioketenes are highly
      reactive, and their intermediate formation may be confirmed by reactions such as
      cycloadditions and thioacylations of nucleophiles. A precursor of
      chlorothioketene, S-(1,2-dichlorovinyl)thioacetate, is readly accessible by the
      reaction of dichloroethyne with thioacetic acid. In presence of base, S-(1,2
      dichlorovinyl)thioacetate is cleaved to chlorothioketene. Chlorothioketene is not
      stable at room temperature and was characterized after transformation to stable
      products by reaction with compounds such as cyclopentadiene, N,N-diethylamine,
      and ethanol. In organic solvents, the cleavage of S-(1, 2
      dichlorovinyl)thioacetate in the presence of cytosine results in N4
      acetylcytosine, N4-(chlorothioacetyl)cytosine, and small amounts of 3-(N4
      thioacetyl)cytosine. No reaction products were seen with guanosine, adenosine,
      and thymidine under identical conditions. When cytosine was reacted with S-(1,2
      dichlorovinyl)thioacetate in aqueous solutions, only N4-acetylcytosine was
      formed. N4-(Chlorothioacetyl)cytosine and 3-(N4-thioacetyl)cytosine were not
      detected even when using a very sensitive method, derivatization with
      pentafluorobenzyl bromide and electron capture mass spectrometry with a detection
      limit of 50 fmol/microliter of injection volume. Aqueous solutions of DNA cleave
      S-(1, 2-dichlorovinyl)thioacetate to give N4-acetyldeoxycytidine in DNA, but
      chlorothioketene adducts of deoxynucleosides were also not detected in these
      experiments. These results confirm the electrophilic reactivity of
      chlorothioketene toward nucleophilic groups of DNA constituents in inert solvents
      but also demonstrate that the formation of DNA adducts under physiological
      conditions likely is not efficient. Therefore, DNA adducts may not represent
      useful biomarkers of exposure and biochemical effects for trichloroethene.

PMID- 9760284
TI  - DNA damage by tert-butoxyl radicals generated in the photolysis of a water
      soluble, DNA-binding peroxyester acting as a radical source.
AB  - The photolysis of the water-soluble perester 1 leads to tert-butoxyl radicals as
      confirmed by EPR studies with the spin trap 5, 5-dimethylpyrroline N-oxide
      (DMPO). In the presence of DNA, oxidative cleavage of the latter was demonstrated
      by the formation of strand breaks in supercoiled pBR 322 DNA and by a substantial
      decrease of the melting temperature of salmon testes DNA. Guanidine, released
      from, for example, oxazolone and oxoimidazolidine on base treatment, was observed
      with calf thymus DNA and 2'-deoxyguanosine. These DNA modifications were
      effectively inhibited by the radical scavenger di-tert-butylcresol or the
      hydrogen atom donor glutathione. Photosensitization by the arene chromophore was
      excluded since the corresponding ester 2 caused no DNA damage, nor were the
      photoproducts of the perester 1 active. The efficacy of the perester 1 in
      oxidizing DNA derives from the fact that the tert-butoxyl radicals are
      photolytically generated in the immediate vicinity of the DNA, due to
      electrostatic binding of the cationic perester to the DNA, as confirmed by
      fluorescence measurements. These results demonstrate that the photolysis of
      perester 1 provides a suitable source of tert-butoxyl radicals in aqueous media,
      a necessary prerequisite for biochemical investigations.

PMID- 9760285
TI  - Mechanism for inhibition of thyroid peroxidase by leucomalachite green.
AB  - The triphenylmethane dye, malachite green (MG), is used to treat and prevent
      fungal and parasitic infections in the aquaculture industry. It has been reported
      that the reduced metabolite of MG, leucomalachite green (LMG), accumulates in the
      tissues of fish treated with MG. MG is structurally related to other
      triphenylmethane dyes (e.g., gentian violet and pararosaniline) that are
      carcinogenic in the liver, thyroid, and other organs of experimental animals. The
      ability of LMG to inhibit thyroid peroxidase (TPO), the enzyme that catalyzes the
      iodination and coupling reactions required for thyroid hormone synthesis, was
      determined in this study. LMG inhibited TPO-catalyzed tyrosine iodination (half
      maximal inhibition at ca. 10 microM). LMG also inhibited the TPO-catalyzed
      formation of thyroxine in low-iodine human goiter thyroglobulin (half-maximal
      inhibition at ca. 10 microM) using a model system that measures simultaneous
      iodination and coupling. Direct inhibition of the coupling reaction by LMG was
      shown using a coupling-only system containing chemically preiodinated
      thyroglobulin as the substrate. Incubation of LMG with TPO, iodide, and tyrosine
      in the presence of a H2O2-generating system yielded oxidation products that were
      identified by using on-line LC/APCI-MS as desmethyl LMG, 2desmethyl LMG,
      3desmethyl LMG, MG, and MG N-oxide. Similar products from LMG were observed in
      incubations with TPO and H2O2 alone. These findings suggest that the anti-thyroid
      effects (increased serum thyroid-stimulating hormone and decreased serum
      thyroxine) observed in rats treated with LMG result from blockade of hormone
      synthesis through alternate substrate inhibition and that chronic exposure could
      cause thyroid follicular cell tumors through a hormonal mechanism. The observed
      TPO-catalyzed oxidative demethylation of LMG to a primary arylamine also suggests
      a genotoxic mechanism for tumor formation is possible.

PMID- 9760286
TI  - The equine estrogen metabolite 4-hydroxyequilenin causes DNA single-strand breaks
      and oxidation of DNA bases in vitro.
AB  - Premarin (Wyeth-Ayerst) is the estrogen replacement treatment of choice and
      continues to be one of the most widely dispensed prescriptions in North America.
      In addition to endogenous estrogens, Premarin contains unsaturated equine
      estrogens, including equilenin [1,3,5(10),6,8-estrapentaen-3-ol-17-one]. In
      previous work, we showed that the equilenin metabolite 4-hydroxyequilenin (4
      OHEN) can be autoxidized to 4-OHEN-o-quinone which readily entered into a redox
      couple with the semiquinone radical catalyzed by NAD(P)H, P450 reductase, or
      quinone reductase, resulting in generation of reactive oxygen species [Shen, L.,
      Pisha, E., Huang, Z., Pezzuto, J. M., Krol, E., Alam, Z., van Breemen, R. B., and
      Bolton, J. L. (1997) Carcinogenesis 18, 1093-1101]. As oxidative damage to DNA by
      reactive oxygen species generated by redox active compounds has been proposed to
      lead to tumor formation, we investigated whether 4-OHEN could cause DNA damage.
      We treated lambda phage DNA with 4-OHEN and found that extensive single-strand
      breaks could be obtained with increasing concentrations of 4-OHEN as well as
      increasing incubation times. If scavengers of reactive oxygen species are
      included in the incubations, DNA could be completely protected from 4-OHEN
      mediated damage. In contrast, NADH and CuCl2 enhanced the ability of 4-OHEN to
      cause DNA single-strand breaks presumably due to redox cycling between 4-OHEN and
      the semiquinone radical generating hydrogen peroxide and ultimately copper
      peroxide complexes. We also confirmed that 4-OHEN could oxidize DNA bases since
      hydrolysis of 4-OHEN-treated calf thymus DNA and HPLC separation with
      electrospray MS detection revealed oxidized deoxynucleosides, including 8
      oxodeoxyguanosine and 8-oxodeoxyadenosine. Our data suggest that DNA single
      strand breaks and oxidation of DNA bases by 4-OHEN could contribute to the
      carcinogenic mechanism(s) of equine estrogens.

PMID- 9760287
TI  - Modes of myocardial cell injury and cell death in ischemic heart disease.

PMID- 9760288
TI  - Reduction of recurrent ischemia with abciximab during continuous ECG-ischemia
      monitoring in patients with unstable angina refractory to standard treatment
      (CAPTURE).
AB  - BACKGROUND: In the CAPTURE (c7E3 Fab Anti Platelet Therapy in Unstable REfractory
      angina) trial, 1265 patients with refractory unstable angina were treated with
      abciximab or placebo, in addition to standard treatment from 16 to 24 hours
      preceding coronary intervention through 1 hour after intervention. To investigate
      the incidence of recurrent ischemia and the ischemic burden, a subset of 332
      patients (26%) underwent continuous vector-derived 12-lead ECG-ischemia
      monitoring. METHODS AND RESULTS: Patients were monitored from start of treatment
      through 6 hours after coronary intervention. Ischemic episodes were detected in
      31 (18%) of the 169 abciximab and in 37 (23%) of the 163 placebo patients (NS).
      Only 9 (5%) of abciximab versus 22 (14%) of placebo patients had >/=2 ST episodes
      (P<0.01). In patients with ischemia, abciximab significantly reduced total
      ischemic burden (P<0.02), which was calculated alternatively as the total
      duration of ST episodes per patient, the area under the curve of the ST vector
      magnitude during episodes, or the sum of the areas under the curves of 12 leads
      during episodes. Twenty-one patients (6%) suffered a myocardial infarction (MI)
      (18) or died (3) within 5 days of treatment. The presence of asymptomatic and
      symptomatic ST episodes during the monitoring period preceding coronary
      intervention was associated with an increased relative risk of these events of
      3.2 (95% CI 1.4, 7.4) and 4.1 (95% CI 1.4, 12.2), respectively. CONCLUSIONS:
      Recurrent ischemia predicts MI or death within 5 days of follow-up. Treatment
      with abciximab is associated with a reduction of frequent ischemia and a
      reduction of total ischemic burden in patients with refractory unstable angina.
      As such, patients with ischemia derive particularly high benefit from abciximab.

PMID- 9760289
TI  - Risk profile and prediction of long-term ischemic stroke mortality: a 21-year
      follow-up in the Israeli Ischemic Heart Disease (IIHD) Project.
AB  - BACKGROUND: Multinational comparisons demonstrate marked ethnic and regional
      variation in stroke mortality and risk-factor distribution. We assessed the role
      of ethnicity and estimated the cumulative effect of multiple risk factors on long
      term ischemic stroke mortality. METHODS AND RESULTS: Civil servants and municipal
      employees in Israel (n=9734 men; age, >/=42 years), chosen by stratified sampling
      in 6 prespecified areas of birth (those born in Israel and those who were
      immigrants from 5 other regional-ethnic strata), were included in the Israeli
      Ischemic Heart Disease (IIHD) Project. Over a 21-year follow-up period, age
      adjusted mortality rates per 10 000 person-years attributed to ischemic stroke
      (n=282; International Classification of Diseases [ICD]-9 codes 433 to 438) were
      higher among immigrants to Israel from northern Africa and the Mideast (17.1 to
      19.0), than from 3 parts of Europe (11.3 to 12.4). Crude rates per 1000 subjects
      observed in those born in Asia or Africa (29.4 to 31.2) exceeded rates predicted
      by risk-factor profiles (21.4 to 24.9). Adjusted hazard ratios were 3.00 for age
      (per 10 years), 2.15 for left ventricular hypertrophy, 1.69 for systolic blood
      pressure (BP, per 20 mm Hg), 1.86 for diabetes mellitus, 1.83 for peripheral
      vascular disease, 1.79 for smoking (>20 cigarettes per day), 1.51 for coronary
      heart disease, 1.16 for percent cholesterol contained in the HDL fraction (%HDL,
      per 5% decrease), and 1.88 for diastolic BP (per 12 mm Hg; assessed in an
      alternative model). Accounting for regression dilution bias and assessed from
      repeat measurements, we found that hazard ratio estimates associated with
      diastolic BP, systolic BP, and percent HDL (per increments described) increased
      to 3.22, 2.23, and 1.23, respectively. Ischemic stroke mortality rates were 30
      fold greater among subjects at the highest versus the lowest quintile of
      predicted probability according to risk-factor profiles (81.2 versus 2.6 per 1000
      subjects). CONCLUSIONS: Assessment of multiple risk factors provides useful
      quantitative prediction of long-term ischemic stroke mortality risk. Regional
      ethnic variations are consistent with a hypothesis that other, undetermined
      inherent genetic or sociocultural factors act to increase ischemic stroke
      mortality rates in immigrants to Israel from the Mideast and northern Africa over
      that predicted by conventional risk factors.

PMID- 9760290
TI  - S-nitrosoglutathione reduces the rate of embolization in humans.
AB  - BACKGROUND: Antiplatelet agents presently used in the secondary prevention of
      cardiovascular disease fail to prevent the majority of cases of recurrent stroke
      and systemic embolization. An evaluation of the efficacy of new agents is
      hampered by a lack of in vivo models in humans. Asymptomatic cerebral embolic
      signals (ES) may be detected with the use of transcranial Doppler
      ultrasonography. These signals are particularly common after carotid
      endarterectomy, and this provides a situation in which new antiplatelet agents
      can be evaluated. With this model, we determined the effectiveness of S
      nitrosoglutathione (GSNO), a nitric oxide donor with relative platelet
      specificity, in reducing cerebral embolization. METHODS AND RESULTS: Transcranial
      Doppler ultrasound recordings from the ipsilateral middle cerebral artery were
      made after carotid endarterectomy in 12 control patients and 12 patients
      receiving intravenous GSNO from the induction of anesthesia until 2 hours after
      skin closure. Recording times were 0.5 to 3.5, 6 to 7, and 24 to 25 hours after
      skin closure. The Doppler signal was recorded onto tape, and analysis for ES was
      performed, with the investigators blinded to treatment group. All patients
      received aspirin 300 mg/d before surgery and 5000 IU of heparin during surgery.
      The median (range) number of ES detected during the initial 3-hour postoperative
      recording was markedly reduced in the GSNO group compared with the control group:
      7.5 (0 to 61) versus 38.5 (1 to 219) (P=0.018). This difference persisted until 6
      hours after surgery. CONCLUSIONS: Despite the administration of aspirin and
      heparin, frequent embolization occurred and was markedly reduced after the
      administration of GSNO. This demonstrates the potential use of platelet-specific
      nitric oxide donors in the treatment of thromboembolic disease. This model of
      cerebral embolism may allow determination of the effectiveness of new
      antiplatelet agents in humans.

PMID- 9760291
TI  - Prediction of 30-day mortality among patients with thrombolysis-related
      intracranial hemorrhage.
AB  - BACKGROUND: Limited information exists on risk factors for mortality after
      thrombolysis-related intracranial hemorrhage. We wished to determine the
      characteristics associated with 30-day mortality after thrombolysis-related
      intracranial hemorrhage. METHODS AND RESULTS: We performed an observational
      analysis within a randomized trial of 4 thrombolytic therapies, conducted in 1081
      hospitals in 15 countries. Patients presented with ST-segment elevation within 6
      hours of symptom onset. Our population was composed of the 268 patients who had
      primary intracranial hemorrhage after thrombolysis. With univariable and
      multivariable analyses, we identified clinical and brain imaging characteristics
      that would predict 30-day mortality among these patients. CT or MRI were
      available for 240 patients (90%). The 30-day mortality rate was 59.7%. Glasgow
      Coma Scale score, age, time from thrombolysis to symptoms of intracranial
      hemorrhage, hydrocephalus, herniation, mass effect, intraventricular extension,
      and volume and location of intracranial hemorrhage were significant univariable
      predictors. Multivariable analysis of 170 patients with complete data, 98 of whom
      died, identified the following independent, significant predictors: Glasgow Coma
      Scale score (chi2, 19.3; P<0. 001), time from thrombolysis to intracranial
      hemorrhage (chi2, 15.8; P<0.001), volume of intracranial hemorrhage (chi2, 11.6;
      P<0.001), and baseline clinical predictors of mortality in the overall GUSTO-I
      trial (chi2, 10.3; P=0.001). The final model had a C-index of 0.931. CONCLUSIONS:
      This model provides excellent discrimination between patients who are likely to
      live and those who are likely to die after thrombolytic-related intracranial
      hemorrhage; this may aid in making decisions about the appropriate level of care
      for such patients.

PMID- 9760292
TI  - Molecular basis of transient outward potassium current downregulation in human
      heart failure: a decrease in Kv4.3 mRNA correlates with a reduction in current
      density.
AB  - BACKGROUND: Despite advances in medical therapy, congestive heart failure remains
      a major cause of death in the developed world. A disproportionate number of the
      deaths of patients with heart failure are sudden and presumed to be arrhythmic.
      Heart failure in humans and in animal models is associated with prolongation of
      the action potential duration (APD), the result of downregulation of K+ currents
      prominently, the Ca2+-independent transient outward current (Ito). The mechanism
      for the reduction of Ito in heart failure is unknown. The K+ channel alpha
      subunit Kv4.3, a homolog of the Drosophila Shal family, is most likely to encode
      all or part of the native cardiac Ito in humans. METHODS AND RESULTS: We used
      ribonuclease protection assays and whole-cell electrophysiological recording to
      study changes in the level of Kv4.3 mRNA and Ito in human tissues and isolated
      ventricular myocytes, respectively. We found that the level of Kv4.3 mRNA
      decreased by 30% in failing hearts compared with nonfailing controls.
      Furthermore, this reduction correlated with the reduction in peak Ito density
      measured in ventricular myocytes isolated from adjacent regions of the heart.
      There was no significant change in the steady-state level of any other mRNA
      studied (HERG, Kv1.4, Kir2.1, Kvss1.3, and the alpha1C subunit of the Ca2+
      channel). mRNAs encoding Kv1.2, Kv1.5, and Kv2.1 were found in low abundance in
      human ventricle. CONCLUSIONS: These data provide further support for the
      hypothesis that Kv4.3 encodes all or part of the native cardiac Ito in humans and
      that part of the downregulation of this current in heart failure may be
      transcriptionally regulated.

PMID- 9760293
TI  - Central vagotonic effects of atropine modulate spectral oscillations of
      sympathetic nerve activity.
AB  - BACKGROUND: Low-dose atropine causes bradycardia either by acting on the
      sinoatrial node or by its effects on central muscarinic receptors increasing
      vagal activity. Any central muscarinic effects of high-dose atropine on RR
      interval are masked by peripheral muscarinic blockade at the sinoatrial node,
      which causes tachycardia. Effects of central parasympathetic activation on
      sympathetic activity are not known. METHODS AND RESULTS: Using power spectral
      analysis of RR interval, intra-arterial blood pressure, respiration, and muscle
      sympathetic nerve activity (MSNA), we examined the effects of both low (2
      microgram/kg IV) and high (15 microgram/kg IV) doses of atropine. After low-dose
      atropine, RR increased by 9+/-1% (P<0.0001), the low-frequency (LF) component (in
      normalized units, NU) of RR variability decreased by -32+/-8%, and the high
      frequency (HF)NU component increased (+74+/-19%); hence, LF/HF of RR variability
      fell by 52+/-10% (all P<0.01). Although overall MSNA did not change, LFNU of MSNA
      decreased (-15+/-5%), HFNU of MSNA increased (+31+/-3%), and LF/HF of MSNA fell (
      41+/-8%) (all P<0.01). After high-dose atropine, LFNU of MSNA decreased (-17+/
      12%), HFNU of MSNA increased (+22+/-3%), and LF/HF of MSNA fell (-51+/-21%) (all
      P<0.02). CONCLUSIONS: Increasing central parasympathetic activity with low-dose
      atropine is associated with an increase in the HF and a decrease in the LF
      oscillations of both RR interval and MSNA variability. High-dose atropine
      similarly induces an increase in the HF and a decrease in the LF components of
      MSNA variability. Thus, central parasympathetic activation is able to modulate
      the oscillatory characteristics of sympathetic nerve traffic to peripheral blood
      vessels.

PMID- 9760294
TI  - Dysfunctional voltage-gated K+ channels in pulmonary artery smooth muscle cells
      of patients with primary pulmonary hypertension.
AB  - BACKGROUND: Primary pulmonary hypertension (PPH) is a rare disease of unknown
      cause. Although PPH and secondary pulmonary hypertension (SPH) share many
      clinical and pathological characteristics, their origins may be disparate. In
      pulmonary artery smooth muscle cells (PASMCs), the activity of voltage-gated K+
      (KV) channels governs membrane potential (Em) and regulates cytosolic free Ca2+
      concentration ([Ca2+]cyt). A rise in [Ca2+]cyt is a trigger of vasoconstriction
      and a stimulus of smooth muscle proliferation. METHODS AND RESULTS: Fluorescence
      microscopy and patch clamp techniques were used to measure [Ca2+]cyt, Em, and KV
      currents in PASMCs. Mean pulmonary arterial pressures were comparable (46+/-4 and
      53+/-4 mm Hg; P=0.30) in SPH and PPH patients. However, PPH-PASMCs had a higher
      resting [Ca2+]cyt than cells from patients with SPH and nonpulmonary hypertension
      disease. Consistently, PPH-PASMCs had a more depolarized Em than SPH-PASMCs.
      Furthermore, KV currents were significantly diminished in PPH-PASMCs. Because of
      the dysfunctional KV channels, the response of [Ca2+]cyt to the KV channel
      blocker 4-aminopyridine was significantly attenuated in PPH-PASMCs, whereas the
      response to 60 mmol/L K+ was comparable to that in SPH-PASMCs. CONCLUSIONS: These
      results indicate that KV channel function in PPH-PASMCs is inhibited compared
      with SPH-PASMCs. The resulting membrane depolarization and increase in [Ca2+]cyt
      lead to pulmonary vasoconstriction and PASMC proliferation. Our data suggest that
      defects in PASMC KV channels in PPH patients may be a unique mechanism involved
      in initiating and maintaining pulmonary vasoconstriction and appear to play a
      role in the pathogenesis of PPH.

PMID- 9760295
TI  - Estimation of oxygen delivery in newborns with a univentricular circulation.
AB  - BACKGROUND: The management of neonates with complex congenital anomalies depends
      on careful interpretation of arterial blood gas values. Improved interpretation
      of these oxygen parameters may allow clinicians to avoid unexpected
      cardiovascular events. This study examined whether systemic oxygen delivery (DO2)
      can be maximized by the use of indices derived from oxygen saturation
      measurements in neonates with hypoplastic left heart syndrome. METHODS AND
      RESULTS: For the single-ventricle heart with both circulations in parallel, we
      used a previously developed computer simulation to obtain DO2 as a function of
      systemic arterial (SaO2) and venous (SvO2) oxygen saturation, arteriovenous
      oxygen difference (Sa-vO2), or pulmonary-to-systemic flow ratio (Qp/Qs). We also
      examined the oxygen excess factor, SaO2/Sa-vO2 (Omega). We found that (1) slight
      increases in SaO2 may be associated with large decreases in DO2. (2) Low values
      for SvO2 indicate low values for DO2. (3) Curves for Sa-vO2 and Qp/Qs are
      redundant in the data provided. (Qp/Qs, however, provides these data in more
      physiologically relevant terms.) (4) High values for Qp/Qs (>4) are associated
      with low DO2. (5) Estimating Qp/Qs from oxygen saturation measurements may result
      in errors when pulmonary venous oxygen saturation is not available. (6)
      Maximizing DO2 is extremely difficult using SaO2, SvO2, and Qp/Qs. (7) A linear
      relationship exists between Omega and DO2, and this linear relationship is not
      altered by changes in cardiac output. CONCLUSIONS: Patients with low SvO2 values
      require attention. Ideally, after reducing Qp/Qs to <1.5, Omega might be a better
      index to guide further therapy and maximize DO2. Interventions that increased
      Omega would be considered beneficial, whereas interventions that decreased Omega
      would be considered detrimental.

PMID- 9760296
TI  - Whole-body hyperthermia provides biphasic cardioprotection against
      ischemia/reperfusion injury in the rat.
AB  - BACKGROUND: Hyperthermia increases cardiac tolerance to ischemia/reperfusion
      injury 24 hours after the heat stress. Free radicals and redox mechanisms have
      been implicated in such tolerance. However, the time course and its relation to
      the induction of antioxidative enzymes in the protection induced by whole-body
      hyperthermia against ischemia/reperfusion injury are unknown. METHODS AND
      RESULTS: Hyperthermia was induced in anesthetized rats by placement in a
      temperature-controlled water bath. After the defined recovery interval(s) at room
      temperature, ischemia was induced by occlusion of the left coronary artery for 20
      minutes, followed by reperfusion for 48 hours. The exposure to hyperthermia led
      to a recovery interval- dependent, biphasic reduction in the incidence of
      ventricular fibrillation during ischemia and in the size of the myocardial
      infarct as determined after 48 hours of reperfusion. The time course of the late
      phase (24- to 96-hour recovery interval) but not the early-phase (0.5 hour)
      cardioprotection depended on the degree of hyperthermia. The time course of the
      increase in myocardial manganese superoxide dismutase (Mn-SOD) activity
      corresponded to that of the cardioprotective effects, although an increase in the
      content of Mn-SOD and of heat shock protein 72 corresponded only to the late
      phase effects. Administration of an antioxidant before hyperthermia abolished the
      early- and late-phase cardioprotection and the increase in Mn-SOD activity.
      CONCLUSIONS: THe activation of Mn-SOD mediated by free radical production during
      hyperthermia is important in the acquisition of early-phase and late-phase
      cardioprotection against ischemia/reperfusion injury in rats.

PMID- 9760297
TI  - "Apoptotic" myocytes in infarct area in rabbit hearts may be oncotic myocytes
      with DNA fragmentation: analysis by immunogold electron microscopy combined with
      In situ nick end-labeling.
AB  - BACKGROUND: Modes of cell death have been defined morphologically as apoptosis
      and oncosis. Infarcted myocytes have been reported to show apoptosis, as revealed
      by DNA fragmentation by DNA ladder and by in situ terminal deoxynucleotidyl
      transferase-mediated dUTP nick end-labeling (TUNEL) at the light microscopic
      level. We investigated whether TUNEL-positive infarcted myocytes have apoptotic
      or oncotic ultrastructures by using electron microscopic TUNEL, which can
      simultaneously observe the ultrastructure and DNA fragmentation of the same
      myocytes. METHODS AND RESULTS: Thirty rabbits were divided into 5 groups (n=6
      each) that were subjected to a sham operation or to 30-minute ischemia followed
      by 0-minute, 30-minute, 2-hour, or 4-hour reperfusion of a coronary artery. In
      the 2- and 4-hour reperfusion groups only, DNA electrophoresis showed a ladder
      pattern, and the light microscopic TUNEL finding was positive in the nuclei of
      myocytes localized in the infarcted area (6+/-2% and 11+/-3%, respectively).
      Electron microscopic TUNEL showed that nuclei with a significant accumulation of
      immunogold particles (indicating an electronic microscopic TUNEL-positive result)
      were observed only in the infarcted myocytes with irreversibly oncotic
      ultrastructures that were found in the hearts of the 2- and 4-hour reperfusion
      groups (41+/-3% and 83+/-4%, respectively). Irreversibly oncotic myocytes
      (indicated by swelling, inhomogeneously clumped chromatin in nuclei, dense bodies
      in mitochondria, and/or ruptured plasma membranes) were also seen in the 0- and
      30-minute reperfusion groups, which did not exhibit TUNEL-positive myocytes.
      There was no evidence of apoptotic ultrastructures in the myocytes. CONCLUSIONS:
      DNA fragmentation occurs in the myocytes that had already shown irreversibly
      oncotic, but not apoptotic, ultrastructures with ischemia and/or reperfusion.
      Therefore, DNA fragmentation itself does not always mean apoptosis, and so-called
      apoptotic infarcted myocytes may belong to a category of cell death other than
      apoptosis.

PMID- 9760298
TI  - Effect of platelet activation on coronary collateral blood flow.
AB  - BACKGROUND: The platelet products thromboxane A2 and serotonin have been shown to
      cause constriction of well-developed coronary collateral vessels. This study was
      performed to determine whether intravascular platelet activation produced with
      platelet activating factor (PAF) can cause a decrease in coronary collateral
      blood flow. METHODS AND RESULTS: Collateral vessel growth was induced by
      embolization of a hollow stainless steel plug into the left anterior descending
      coronary artery (LAD) of adult dogs. The animals were returned to the laboratory
      3 to 6 weeks later for surgical instrumentation and measurement of collateral
      blood flow. Collateral flow was assessed by measuring retrograde blood flow from
      the cannulated collateral-dependent artery. PAF (10 nmol) was injected into the
      left main coronary artery to allow products of platelet activation to reach
      collateral vessels arising from the left coronary system. PAF caused a
      vasoconstrictor response, which became maximal 3 minutes after injection and
      resulted in a 40.3+/-7.4% decrease in retrograde blood flow (32.1+/-2.1 to 19.6+/
      3.2 mL/min; P<0.05). By 15 minutes after the PAF injection, both retrograde blood
      flow and transcollateral resistance had returned to normal. After pretreatment
      with the thromboxane A2 receptor antagonist SQ30, 741, the vasoconstrictor
      response to PAF was abolished and, in contrast to the decrease in retrograde
      blood flow from PAF alone, a weak vasodilator effect was unmasked. CONCLUSIONS:
      PAF caused a decrease in coronary collateral blood flow. This vasoconstrictor
      response required the participation of thromboxane A2.

PMID- 9760299
TI  - Gene therapy with extracellular superoxide dismutase attenuates myocardial
      stunning in conscious rabbits.
AB  - BACKGROUND: Administration of Cu/Zn superoxide dismutase (SOD) without catalase
      fails to alleviate myocardial stunning, but extracellular SOD (Ec-SOD) may be
      more effective because it binds to heparan sulfate proteoglycans on the cellular
      glycocalyx. We therefore used in vivo gene transfer to increase systemic levels
      of Ec-SOD and determined whether this gene therapy protects against myocardial
      stunning. METHODS AND RESULTS: The cDNA for human Ec-SOD was cloned behind the
      cytomegalovirus (CMV) promoter and incorporated into a replication-deficient
      adenovirus (Ad5/CMV/Ec-SOD). Injection of this virus (2x10(8) pfu/kg IV) produced
      high levels of Ec-SOD in the liver, which could be redistributed to the heart and
      other organs by injection of heparin. Conscious rabbits underwent a sequence of
      six 4-minute coronary occlusion/4-minute reperfusion cycles for 3 consecutive
      days starting 3 days after intravenous injection of Ad5/CMV/Ec-SOD or
      Ad5/CMV/nls/LacZ (negative control). Both groups were given heparin (2000 U/kg
      IV) 2 hours before the first sequence of occlusions. The severity of myocardial
      stunning was measured as the total deficit of LV wall thickening after the last
      reperfusion. On day 1, the total deficit of wall thickening was markedly
      decreased in Ad5/CMV/Ec-SOD rabbits versus controls and similar to that seen on
      days 2 and 3 in controls. CONCLUSIONS: The results demonstrate that in vivo gene
      transfer of the cDNA encoding Ec-SOD provides the heart with substantial
      protection against myocardial stunning without the need for concomitant
      administration of catalase. The present observations provide the basis for
      controlling gene therapy at the posttranslational level and for simultaneously
      protecting multiple organs from oxidant stress.

PMID- 9760300
TI  - Lewis Atterbury Conner: appreciation and bibliography.

PMID- 9760301
TI  - Progress in device technology.

PMID- 9760302
TI  - Restrictive cardiomyopathy secondary to Fabry's disease.

PMID- 9760303
TI  - Impact of laboratory molecular diagnosis on contemporary diagnostic criteria for
      genetically transmitted cardiovascular diseases: hypertrophic cardiomyopathy,
      long-QT syndrome, and marfan syndrome : A statement for healthcare professionals
      from the councils on clinical cardiology, cardiovascular disease in the young,
      and basic science, american heart association 

PMID- 9760304
TI  - Obesity : impact on cardiovascular disease 

PMID- 9760305
TI  - Comparison between the uptake of nitrous oxide and nitric oxide in the human
      nose.

PMID- 9760306
TI  - Comparison between the uptake of nitrous oxide and nitric oxide in the human
      nose.
AB  - The absorption of nitrous oxide (N2O) during unidirectional flow was compared
      with the rate of uptake of nitric oxide (NO). At flow rates of 10, 20, and 60
      ml/min from one nostril to the other, with the soft palate closed, the N2O
      reached a steady-state rate of absorption in 5-15 min. The mean superficial
      capillary blood flow (n = 5) calculated from solubility and the steady-state rate
      of N2O absorption ranged from 13.3 to 15.9 ml/min. The relation between
      absorption of N2O in the nose and capillary blood flow fits a ventilation
      perfusion model used by others to describe uptake of inert, soluble gases in the
      rat nose. By contrast, the rate of uptake of NO gas, which is chemically
      reactive, is 25-31 times as great as predicted by just its blood-to-air partition
      coefficient. Exogenous NO (16.9 parts/million) did not induce nasal vasodilation
      as measured with laser Doppler and N2O absorption methods. The difference between
      the measured rate of uptake of NO and the rate of uptake attributable to its
      partition coefficient in blood at the rate of blood flow calculated from N2O
      uptake is probably due to chemical reaction of NO in mucous secretions, nasal
      tissues, and capillary blood.

PMID- 9760307
TI  - Exertional fatigue, sleep loss, and negative energy balance increase
      susceptibility to hypothermia.
AB  - The purpose of this study was to determine how chronic exertional fatigue and
      sleep deprivation coupled with negative energy balance affect thermoregulation
      during cold exposure. Eight men wearing only shorts and socks sat quietly during
      4-h cold air exposure (10 degreesC) immediately after (<2 h, A) they completed 61
      days of strenuous military training (energy expenditure approximately 4,150
      kcal/day, energy intake approximately 3,300 kcal/day, sleep approximately 4
      h/day) and again after short (48 h, SR) and long (109 days, LR) recovery. Body
      weight decreased 7.4 kg from before training to A, then increased 6.4 kg by SR,
      with an additional 6.4 kg increase by LR. Body fat averaged 12% during A and SR
      and increased to 21% during LR. Rectal temperature (Tre) was lower before and
      during cold air exposure for A than for SR and LR. Tre declined during cold
      exposure in A and SR but not LR. Mean weighted skin temperature (Tsk) during cold
      exposure was higher in A and SR than in LR. Metabolic rate increased during all
      cold exposures, but it was lower during A and LR than SR. The mean body
      temperature (0.67 Tre + 0.33 Tsk) threshold for increasing metabolism was lower
      during A than SR and LR. Thus chronic exertional fatigue and sleep loss, combined
      with underfeeding, reduced tissue insulation and blunted metabolic heat
      production, which compromised maintenance of body temperature. A short period of
      rest, sleep, and refeeding restored the thermogenic response to cold, but thermal
      balance in the cold remained compromised until after several weeks of recovery
      when tissue insulation had been restored.

PMID- 9760308
TI  - Increased GLUT-4 translocation mediates enhanced insulin sensitivity of muscle
      glucose transport after exercise.
AB  - The purpose of this study was to determine whether the increase in insulin
      sensitivity of skeletal muscle glucose transport induced by a single bout of
      exercise is mediated by enhanced translocation of the GLUT-4 glucose transporter
      to the cell surface. The rate of 3-O-[3H]methyl-D-glucose transport stimulated by
      a submaximally effective concentration of insulin (30 microU/ml) was
      approximately twofold greater in the muscles studied 3.5 h after exercise than in
      those of the sedentary controls (0.89 +/- 0.10 vs. 0.43 +/- 0.05 micromol . ml-1
      . 10 min-1; means +/- SE for n = 6/group). GLUT-4 translocation was assessed by
      using the ATB-[2-3H]BMPA exofacial photolabeling technique. Prior exercise
      resulted in greater cell surface GLUT-4 labeling in response to submaximal
      insulin treatment (5.36 +/- 0.45 dpm x 10(3)/g in exercised vs. 3.00 +/- 0.38 dpm
      x 10(3)/g in sedentary group; n = 10/group) that closely mirrored the increase in
      glucose transport activity. The signal generated by the insulin receptor, as
      reflected in the extent of insulin receptor substrate-1 tyrosine phosphorylation,
      was unchanged after the exercise. We conclude that the increase in muscle insulin
      sensitivity of glucose transport after exercise is due to translocation of more
      GLUT-4 to the cell surface and that this effect is not due to potentiation of
      insulin-stimulated tyrosine phosphorylation.

PMID- 9760309
TI  - Force heterogeneity in a two-dimensional network model of lung tissue elasticity.
AB  - We have developed a model of forces developed in lung tissue in which the stress
      bearing units are heterogeneous. Each element of the fiber network is composed of
      an idealized elastin and collagen element in parallel. Elastin is represented by
      linear springs and collagen by stiff strings that extend without resistance until
      taut. The model can quantitatively account for the nonlinear shape of the length
      tension curve of lung tissue strips when the knee lengths of the collagen fibers
      are distributed according to an inverse power law. The novel feature of this
      model is that as macroscopic strain increases the load is carried by
      progressively fewer elements with progressively higher forces, and preferential
      pathways of force transmission emerge within the matrix. The topology of these
      self-organizing pathways of force transmission takes the rough appearance of
      cracks, but, unlike real cracks, they represent the locus of force concentration
      rather than force release.

PMID- 9760310
TI  - Nonisometric behavior of fascicles during isometric contractions of a human
      muscle.
AB  - Fascicle length, pennation angle, and tendon elongation of the human tibialis
      anterior were measured in vivo by ultrasonography. Subjects (n = 9) were
      requested to develop isometric dorsiflexion torque gradually up to maximal at the
      ankle joint angle of 20 degrees plantarflexion from the anatomic position.
      Fascicle length shortened from 90 +/- 7 to 76 +/- 7 (SE) mm, pennation angle
      increased from 10 +/- 1 to 12 +/- 1 degrees, and tendon elongation increased up
      to 15 +/- 2 mm with graded force development up to maximum. The tendon stiffness
      increased with increasing tendon force from 10 N/mm at 0-20 N to 32 N/mm at 240
      260 N. Young's modulus increased from 157 MPa at 0-20 N to 530 MPa at 240-260 N.
      It can be concluded that, in isometric contractions of a human muscle, mechanical
      work, some of which is absorbed by the tendinous tissue, is generated by the
      shortening of muscle fibers and that ultrasonography can be used to determine the
      stiffness and Young's modulus for human tendons.

PMID- 9760311
TI  - Expiratory flow limitation and intrinsic positive end-expiratory pressure in
      obesity.
AB  - Breathing at very low lung volumes might be affected by decreased expiratory
      airflow and air trapping. Our purpose was to detect expiratory flow limitation
      (EFL) and, as a consequence, intrinsic positive end-expiratory pressure (PEEPi)
      in grossly obese subjects (OS). Eight OS with a mean body mass index (BMI) of 44
      +/- 5 kg/m2 and six age-matched normal-weight control subjects (CS) were studied
      in different body positions. Negative expiratory pressure (NEP) was used to
      determine EFL. In contrast to CS, EFL was found in two of eight OS in the upright
      position and in seven of eight OS in the supine position. Dynamic PEEPi and mean
      transdiaphragmatic pressure (mean Pdi) were measured in all six CS and in six of
      eight OS. In OS, PEEPi increased from 0.14 +/- 0.06 (SD) kPa in the upright
      position to 0.41 +/- 0.11 kPa in the supine position (P < 0.05) and decreased to
      0.20 +/- 0.08 kPa in the right lateral position (P < 0.05, compared with supine),
      whereas, in CS, PEEPi was significantly smaller (<0.05 kPa) in each position. In
      OS, mean Pdi in each position was significantly larger compared with CS. Mean Pdi
      increased from 1.02 +/- 0.32 kPa in the upright position to 1.26 +/- 0.17 kPa in
      the supine position (not significant) and decreased to 1. 06 +/- 0.26 kPa in the
      right lateral position (P < 0.05, compared with supine), whereas there were no
      significant changes in CS. We conclude that in OS 1) tidal breathing can be
      affected by EFL and PEEPi; 2) EFL and PEEPi are promoted by the supine posture;
      and 3) the increased diaphragmatic load in the supine position is, in part,
      related to PEEPi.

PMID- 9760312
TI  - Energy metabolism and interstitial fluid displacement in human gastrocnemius
      during short ischemic cycles.
AB  - Energy metabolism and interstitial fluid displacement were studied in the human
      gastrocnemius during three subsequent 5-min ischemia-reperfusion periods
      [ischemic preconditioning (IP)]. The muscle energy balance was assessed by
      combining near-infrared spectroscopy (NIRS) and 31P-nuclear magnetic resonance
      spectroscopy (31P-NMRS). The interstitial fluid displacement was determined by
      combining NIRS and 23Na-NMRS. No changes in total energy consumption or in the
      fractional contribution of the underlying energy sources (aerobic glycolysis,
      anaerobic glycolysis, and Lohmann reaction) were observed in the muscle during
      the tested IP protocol. Oxygen consumption in the muscle region of interest, as
      estimated by NIRS, was approximately 8 micromol . 100 g-1 . min-1 and did not
      change during IP. Phosphocreatine and ATP concentrations did not change over the
      whole experimental period. A slight but significant (P < 0.05) increase in
      intracellular pH was observed. Compared with the control, a 10% greater
      interstitial fluid content per muscle unit volume was observed at the end of the
      IP protocol. It is concluded that, at variance with cardiac muscle, repeated 5
      min ischemia-reperfusion cycles do not induce metabolic changes in human
      gastrocnemius but alter the interstitial fluid readjustment. The techniques
      developed in the present study may be useful in identifying protocols suitable
      for skeletal muscle preconditioning and to explain the functional basis of this
      procedure.

PMID- 9760313
TI  - Deposition and dispersion of 1-micrometer aerosol boluses in the human lung:
      effect of micro- and hypergravity.
AB  - We performed bolus inhalations of 1-micrometer particles in four subjects on the
      ground (1 G) and during parabolic flights both in microgravity (microG) and in
      approximately 1.6 G. Boluses of approximately 70 ml were inhaled at different
      points in an inspiration from residual volume to 1 liter above functional
      residual capacity. The volume of air inhaled after the bolus [the penetration
      volume (Vp)] ranged from 200 to 1,500 ml. Aerosol concentration and flow rate
      were continuously measured at the mouth. The deposition, dispersion, and position
      of the bolus in the expired gas were calculated from these data. For Vp >/=400
      ml, both deposition and dispersion increased with Vp and were strongly gravity
      dependent, with the greatest deposition and dispersion occurring for the largest
      G level. At Vp = 800 ml, deposition and dispersion increased from 33.9% and 319
      ml in microG to 56.9% and 573 ml at approximately 1.6 G, respectively (P < 0.05).
      At each G level, the bolus was expired at a smaller volume than Vp, and this
      volume became smaller with increasing Vp. Although dispersion was lower in microG
      than in 1 G and approximately 1.6 G, it still increased steadily with increasing
      Vp, showing that nongravitational ventilatory inhomogeneity is partly responsible
      for dispersion in the human lung.

PMID- 9760314
TI  - Augmenting expiratory neuronal activity in sleep and wakefulness and in relation
      to duration of expiration.
AB  - Augmenting expiratory cells (n = 23) were recorded in the rostral medulla of five
      cats in sleep and wakefulness. The objective was to determine the relationship of
      their activity to the duration of expiration (TE) and, particularly, to TE in
      rapid-eye-movement (REM) sleep, when expirations are short and may even cause
      fractionated breathing. Correlation analysis (Kendall's tau) showed no consistent
      relationship in any state between the breath-by-breath mean activity of
      augmenting expiratory cells and TE. This result contradicts predications of an
      inverse relationship between augmenting expiratory activity and TE. Some cells
      (11 of 23) were more active in REM than in non-REM sleep and were active during
      fractionated breathing. This suggests that fractionated breathing in REM sleep is
      caused by short expiratory phases and not by intermittent inhibition of an
      ongoing inspiration.

PMID- 9760316
TI  - Genetic and other determinants of AMP deaminase activity in healthy adult
      skeletal muscle.
AB  - AMPD1 genotype, relative fiber type composition, training status, and gender were
      evaluated as contributing factors to the reported variation in AMP deaminase
      enzyme activity in healthy skeletal muscle. Multifactorial correlative analyses
      demonstrate that AMPD1 genotype has the greatest effect on enzyme activity. An
      AMPD1 mutant allele frequency of 13.7 and a 1.7% incidence of enzyme deficiency
      was found across 175 healthy subjects. Homozygotes for the AMPD1 normal allele
      have high enzyme activities, and heterozygotes display intermediate activities.
      When examined according to genotype, other factors were found to affect
      variability as follows: AMP deaminase activity in homozygotes for the normal
      allele exhibits a negative correlation with the relative percentage of type I
      fibers and training status. Conversely, residual AMP deaminase activity in
      homozygotes for the mutant allele displays a positive correlation with the
      relative percentage of type I fibers. Opposing correlations in different
      homozygous AMPD1 genotypes are likely due to relative fiber-type differences in
      the expression of AMPD1 and AMPD3 isoforms. Gender also contributes to variation
      in total skeletal muscle AMP deaminase activity, with normal homozygous and
      heterozygous women showing only 85-88% of the levels observed in genotype-matched
      men.

PMID- 9760315
TI  - Effects of hyperchloremia on blood oxygen binding in healthy calves.
AB  - Three different levels of hyperchloremia were induced in healthy Friesian calves
      to study the effects of chloride on blood oxygen transport. By infusion, the
      calves received either 5 ml/kg of 0.9% NaCl (low-level hyperchloremia; group A),
      5 ml/kg of 7.5% NaCl (moderate hyperchloremia; group B), or 7.5 ml/kg of 7.5%
      NaCl (high-level hyperchloremia; group C). Blood was sampled from the jugular
      vein and the brachial artery. Chloride concentration, hemoglobin content,
      arterial and venous pH, PCO2, and PO2 were determined. At each time point (0, 15,
      30, 60, and 120 min), the whole blood oxygen equilibrium curve (OEC) was measured
      under standard conditions. In groups B and C, hyperchloremia was accompanied by a
      sustained rightward shift of the OEC, as indicated by the significant increase in
      the standard PO2 at 50% hemoglobin saturation. Infusion of hypertonic saline also
      induced relative acidosis. The arterial and venous OEC were calculated, with body
      temperature, pH, and PCO2 values in arterial and venous blood taken into account.
      The degree of blood desaturation between the arterial and the venous compartments
      [O2 exchange fraction (OEF%)] and the amount of oxygen released at tissue level
      by 100 ml of bovine blood (OEF vol%) were calculated from the arterial and venous
      OEC combined with the PO2 and hemoglobin concentration. The chloride-induced
      rightward shift of the OEC was reinforced by the relative acidosis, but the
      altered PO2 values combined with the lower hemoglobin concentration explained the
      absence of any significant difference in OEF (% and vol%). We conclude that
      infusion of hypertonic saline induces hyperchloremia and acidemia, which can
      explain the OEC rightward shift observed in arterial and peripheral venous blood.

PMID- 9760317
TI  - Differential responses to endurance training in subsarcolemmal and
      intermyofibrillar mitochondria.
AB  - To examine the effect of endurance training (6 wk of treadmill running) on
      regional mitochondrial adaptations within skeletal muscle, subsarcolemmal (SS)
      and intermyofibrillar (IMF) mitochondria were isolated from trained and control
      rat hindlimb muscles. Mitochondrial oxygen consumption (VO2) was measured
      polarographically by using the following substrates: 1 mM pyruvate + 1 mM malate
      (P+M), 10 mM 2-oxoglutarate, 45 microM palmitoyl-DL-carnitine + 1 mM malate, and
      10 mM glutamate. Spectrophotometric assays of cytochrome-c reductase and NAD
      specific isocitrate dehydrogenase (IDH) activity were also performed. Maximal
      (state III) and resting (state IV) VO2 were lower in SS than in IMF mitochondria
      in both trained and control groups. In SS mitochondria, training elicited
      significant 36 and 20% increases in state III VO2 with P+M and glutamate,
      respectively. In IMF mitochondria, training resulted in a smaller (20%), yet
      significant, increase in state III VO2 with P+M as a substrate, whereas state III
      VO2 increased 33 and 27% with 2-oxoglutarate and palmitoyl-DL-carnitine + malate,
      respectively. Within groups, cytochrome-c reductase and IDH activities were lower
      in SS when compared with IMF mitochondria. Training increased succinate
      cytochrome-c reductase in both SS (30%) and IMF mitochondria (28%). IDH activity
      increased 32% in the trained IMF but remained unchanged in SS mitochondria. We
      conclude that endurance training promotes substantial changes in protein
      stoichiometry and composition of both SS and IMF mitochondria.

PMID- 9760318
TI  - Patterned cardiovascular responses to sleep and nonrespiratory arousals in a
      porcine model.
AB  - Patients with obstructive sleep apnea experience marked cardiovascular changes
      with apnea termination. Based on this observation, we hypothesized that sudden
      sleep disruption is accompanied by a specific, patterned hemodynamic response,
      similar to the cardiovascular defense reaction. To test this hypothesis, we
      recorded mean arterial blood pressure, heart rate, iliac blood flow and vascular
      resistance, and renal blood flow and vascular resistance in five pigs
      instrumented with chronic sleep electrodes. Cardiovascular parameters were
      recorded during quiet wakefulness, during non-rapid-eye-movement and rapid-eye
      movement sleep, and during spontaneous and induced arousals. Iliac vasodilation
      (iliac vascular resistance decreased by -29.6 +/- 4.1% of baseline) associated
      with renal vasoconstriction (renal vascular resistance increased by 10.3 +/-
      4.0%), tachycardia (heart rate increase: +23.8 +/- 3.1%), and minimal changes in
      mean arterial blood pressure were the most common pattern of arousal response,
      but other hemodynamic patterns were observed. Similar findings were obtained in
      rapid-eye-movement sleep and for acoustic and tactile arousals. In conclusion,
      spontaneous and induced arousals from sleep may be associated with simultaneous
      visceral vasoconstriction and hindlimb vasodilation, but the response is
      variable.

PMID- 9760319
TI  - Superoxide dismutase restores endothelium-dependent arteriolar dilatation during
      acute infusion of nicotine.
AB  - We previously showed [Am. J. Physiol. 272 (Heart Circ. Physiol. 41): H2337-H2342,
      1997] that nicotine impairs endothelium-dependent arteriolar dilatation. However,
      mechanisms that accounted for the effect of nicotine on endothelium-dependent
      vasodilatation were not examined. Thus the goal of this study was to examine the
      role of oxygen radicals in nicotine-induced impairment of arteriolar reactivity.
      We measured diameter of cheek pouch resistance arterioles (approximately 50
      micrometer diameter) in response to endothelium-dependent (ACh and ADP) and 
      independent (nitroglycerin) agonists before and after infusion of vehicle or
      nicotine in the absence or presence of superoxide dismutase. ACh, ADP, and
      nitroglycerin produced dose-related dilatation of cheek pouch arterioles before
      infusion of vehicle or nicotine. Infusion of vehicle, in the absence or presence
      of superoxide dismutase (150 U/ml), did not alter endothelium-dependent or 
      independent arteriolar dilatation. In contrast, infusion of nicotine (2 microgram
      . kg-1 . min-1) impaired endothelium-dependent, but not -independent, arteriolar
      dilatation. In addition, the effect of nicotine on endothelium-dependent
      vasodilatation was reversed by topical application of superoxide dismutase. We
      suggest that nicotine impairs endothelium-dependent arteriolar dilatation via an
      increase in the synthesis/release of oxygen-derived free radicals.

PMID- 9760320
TI  - Important role of carotid afferents in control of breathing.
AB  - The purpose of the present study was to determine the effect on breathing in the
      awake state of carotid body denervation (CBD) over 1-2 wk after denervation.
      Studies were completed on adult goats repeatedly before and 1) for 15 days after
      bilateral CBD (n = 8), 2) for 7 days after unilateral CBD (n = 5), and 3) for 15
      days after sham CBD (n = 3). Absence of ventilatory stimulation when NaCN was
      injected directly into a common carotid artery confirmed CBD. There was a
      significant (P < 0.01) hypoventilation during the breathing of room air after
      unilateral and bilateral CBD. The maximum PaCO2 increase (8 Torr for unilateral
      and 11 Torr for bilateral) occurred approximately 4 days after CBD. This maximum
      was transient because by 7 (unilateral) to 15 (bilateral) days after CBD, PaCO2
      was only 3-4 Torr above control. CO2 sensitivity was attenuated from control by
      60% on day 4 after bilateral CBD and by 35% on day 4 after unilateral CBD. This
      attenuation was transient, because CO2 sensitivity returned to control temporally
      similar to the return of PaCO2 during the breathing of room air. During mild and
      moderate treadmill exercise 1-8 days after bilateral CBD, PaCO2 was unchanged
      from its elevated level at rest, but, 10-15 days after CBD, PaCO2 decreased
      slightly from rest during exercise. These data indicate that 1) carotid afferents
      are an important determinant of rest and exercise breathing and ventilatory CO2
      sensitivity, and 2) apparent plasticity within the ventilatory control system
      eventually provides compensation for chronic loss of these afferents.

PMID- 9760322
TI  - Effects of ovariectomy and hindlimb unloading on skeletal muscle.
AB  - Female rats (7-8 mo old, n = 40) were randomly placed into the intact control
      (Int) and ovariectomized control (Ovx) groups. Two weeks after ovariectomy,
      animals were further divided into intact 2-wk hindlimb unloaded (Int-HU) and
      ovariectomized hindlimb unloaded (Ovx-HU). We hypothesized that there would be
      greater hindlimb unloading-related atrophy in Ovx than in Int rats. In situ
      contractile tests were performed on soleus (Sol), plantaris (Plan), peroneus
      longus (Per), and extensor digitorum longus (EDL) muscles. Body weight and Sol
      mass were approximately 22% larger in Ovx than in Int group and approximately 18%
      smaller in both HU groups than in Int rats (Ovx x HU interaction, P < 0.05), and
      there was a similar trend in Plan muscle (P < 0.07). There were main effects (P <
      0.05) for both ovariectomy (growth) and hindlimb unloading (atrophy) on
      gastrocnemius mass. Mass of the Per and EDL muscles was unaffected by either
      ovariectomy or hindlimb unloading. Time to peak twitch tension for EDL and one
      half relaxation times for Sol, Plan, Per, and EDL muscles were faster (P < 0.05)
      in Ovx than in Int animals. The results suggest that 1) ovariectomy led to
      similar increases of approximately 20% in body weight and plantar flexor mass; 2)
      hindlimb unloading may have prevented ovariectomy-related muscle growth; 3)
      greater atrophy may have occurred in Sol and Plan of Ovx animals compared with
      controls; and 4) removal of ovarian hormonal influence decreased skeletal muscle
      contraction times.

PMID- 9760321
TI  - Effect of simulated microgravity on vascular contractility.
AB  - Microgravity was simulated in Sprague-Dawley (SD) and Wistar (W) rats by using a
      tail harness to elevate the hindquarters, producing hindlimb unweighting (HU).
      After 20 days of HU treatment, blood vessels from both HU and control rats were
      cut into 3-mm rings and mounted in tissue baths for the measurement of isometric
      contraction. HU treatment decreased the contractile response to 68 mM K+ in
      abdominal aorta from W rats. HU treatment also decreased the contraction to 68 mM
      K+ in carotid arteries from both rat strains and in femoral arteries from W but
      not SD rats. HU treatment reduced the maximal response to norepinephrine in all
      arteries except the femoral from SD rats. HU treatment reduced the maximal
      response of jugular vein from W rats to 68 mM K+ but had no effect on that
      response in femoral vein from either rat strain. HU treatment also had no
      significant effect on the maximal response to norepinephrine in veins. These
      results demonstrate that HU treatment caused a nearly universal reduction of
      contractility in arteries, but generally had no effect in veins.

PMID- 9760323
TI  - Influence of acute lung volume change on contractile properties of human
      diaphragm.
AB  - The effect of stimulus frequency on the in vivo pressure generating capacity of
      the human diaphragm is unknown at lung volumes other than functional residual
      capacity. The transdiaphragmatic pressure (Pdi) produced by a pair of phrenic
      nerve stimuli may be viewed as the sum of the Pdi elicited by the first (T1 Pdi)
      and second (T2 Pdi) stimuli. We used bilateral anterior supramaximal magnetic
      phrenic nerve stimulation and a digital subtraction technique to obtain the T2
      Pdi at interstimulus intervals of 999, 100, 50, 33, and 10 ms in eight normal
      subjects at lung volumes between residual volume and total lung capacity. The
      reduction in T2 Pdi that we observed as lung volume increased was greatest at
      long interstimulus intervals, whereas the T2 Pdi obtained with short
      interstimulus intervals remained relatively stable over the 50% of vital capacity
      around functional residual capacity. For all interstimulus intervals, the total
      pressure produced by the pair decreased as a function of increasing lung volume.
      These data demonstrate that, in the human diaphragm, hyperinflation has a
      disproportionately severe effect on the summation of pressure responses elicited
      by low-frequency stimulations; this effect is distinct from and additional to the
      known length-tension relationship.

PMID- 9760324
TI  - Effect of sodium in a rehydration beverage when consumed as a fluid or meal.
AB  - To investigate the impact of fluid composition on rehydration effectiveness, 30
      subjects (15 men and 15 women) were studied during 2 h of rehydration after a
      2.5% body weight loss. In a randomized crossover design, subjects rehydrated with
      water (H2O), chicken broth (CB: 109.5 mmol/l Na, 25.3 mmol/l K), a carbohydrate
      electrolyte drink (CE: 16.0 mmol/l Na, 3.3 mmol/l K), and chicken noodle soup
      (Soup: 333.8 mmol/l Na, 13.7 mmol/l K). Subjects ingested 175 ml at the start of
      rehydration and 20 min later; H2O was given every 20 min thereafter for a total
      volume equal to body weight loss during dehydration. At the end of the
      rehydration period, plasma volume was not significantly different from
      predehydration values in the CB (-1.6 +/- 1.1%) and Soup (-1.4 +/- 0.9%) trials.
      In contrast, plasma volume remained significantly (P < 0.01) below predehydration
      values in the H2O (-5.6 +/- 1.1%) and CE (-4.2 +/- 1.0%) trials after the
      rehydration period. Urine volume was greater in the CE (310 +/- 30 ml) than in
      the CB (188 +/- 20 ml) trial. Urine osmolality was higher in the CB and Soup
      trials than in the CE trial. Urinary sodium concentration was higher in the Soup
      and CB trials than in the CE and H2O trials. These results provide evidence that
      the inclusion of sodium in rehydration beverages, as well as consumption of a
      sodium-containing liquid meal, increases fluid retention and improves plasma
      volume restoration.

PMID- 9760325
TI  - Fiber type and citrate synthase activity in the human gastrocnemius and vastus
      lateralis with aging.
AB  - The purpose of this study was to determine whether enzymatic and histochemical
      characteristics of human skeletal muscle are altered with aging. Tissues from the
      vastus lateralis (VL) and gastrocnemius were analyzed for citrate synthase (CS)
      activity and fiber type in 55 sedentary men (age range 18-80 yr). In this
      population, CS activity in the gastrocnemius was negatively related to age (r = 
      0. 32, P < 0.05); there was no relationship in the VL. Treadmill-determined
      maximal oxygen consumption was positively related (r = 0.40, P < 0.05) to CS in
      the gastrocnemius but not in the VL. CS activity in the gastrocnemius was 24%
      lower in the oldest (>/=60 yr, n = 10) vs. the youngest (</=30 yr; n = 12) men;
      there was no change in CS activity in the VL with aging. No changes in fiber type
      were evident with age in either muscle. These data suggest a reduction in
      oxidative enzyme activity in human skeletal muscle with the aging process; this
      relationship may be muscle-group specific.

PMID- 9760326
TI  - Endurance in high-fat-fed rats: effects of carbohydrate content and fatty acid
      profile.
AB  - The purpose of this experiment was to study endurance performance and substrate
      storage and utilization in fat- or carbohydrate-fed rats. Ninety-nine rats were
      randomly divided into three groups and over 4 wk were fed either a carbohydrate
      rich [CHO; 10% total energy content in the diet (E%) fat, 20 E% protein, 70 E%
      carbohydrate] diet or one of two fat-rich diets (65 E% fat, 20 E% protein, 15 E%
      carbohydrate) containing either saturated (Sat) or monounsaturated fatty acids
      (Mono). Each dietary group was randomly assigned to a trained (6 days/wk,
      progressive to 60 min, 28 m/min at a 10% incline) or a sedentary group. Rats were
      killed either before or after a treadmill endurance run to exhaustion. Training
      increased endurance (206%), but diet composition did not affect endurance in
      either trained or sedentary rats. beta-Hydroxyacyl-CoA dehydrogenase activity was
      increased in fat-fed but not carbohydrate-fed rats (P < 0.05). Respiratory
      exchange ratio during the initial phase of exercise was lower after the Mono
      compared with the Sat diet (P < 0. 05) and higher after the CHO than the Sat diet
      (P < 0.05). Thus adaptation to a high-fat diet containing a moderate amount of
      carbohydrates did not induce enhanced endurance in either trained or untrained
      rats; however, substrate utilization was modulated by both amount and type of
      dietary fat during the initial stage of exercise in trained and sedentary rats.

PMID- 9760327
TI  - Creatine supplementation and age influence muscle metabolism during exercise.
AB  - Young [n = 5, 30 +/- 5 (SD) yr] and middle-aged (n = 4, 58 +/- 4 yr) men and
      women performed single-leg knee-extension exercise inside a whole body magnetic
      resonance system. Two trials were performed 7 days apart and consisted of two 2
      min bouts and a third bout continued to exhaustion, all separated by 3 min of
      recovery. 31P spectra were used to determine pH and relative concentrations of
      Pi, phosphocreatine (PCr), and beta-ATP every 10 s. The subjects consumed 0.3 g .
      kg-1 . day-1 of a placebo (trial 1) or creatine (trial 2) for 5 days before each
      trial. During the placebo trial, the middle-aged group had a lower resting PCr
      compared with the young group (35.0 +/- 5.2 vs. 39.5 +/- 5.1 mmol/kg, P < 0.05)
      and a lower mean initial PCr resynthesis rate (18.1 +/- 3.5 vs. 23.2 +/- 6.0 mmol
      . kg-1 . min-1, P < 0.05). After creatine supplementation, resting PCr increased
      15% (P < 0.05) in the young group and 30% (P < 0.05) in the middle-aged group to
      45.7 +/- 7.5 vs. 45.7 +/- 5.5 mmol/kg, respectively. Mean initial PCr resynthesis
      rate also increased in the middle-aged group (P < 0.05) to a level not different
      from the young group (24.3 +/- 3.8 vs. 24.2 +/- 3.2 mmol . kg-1 . min-1). Time to
      exhaustion was increased in both groups combined after creatine supplementation
      (118 +/- 34 vs. 154 +/- 70 s, P < 0.05). In conclusion, creatine supplementation
      has a greater effect on PCr availability and resynthesis rate in middle-aged
      compared with younger persons.

PMID- 9760328
TI  - Moderate exercise increases postexercise thresholds for vasoconstriction and
      shivering.
AB  - The purpose of this study was to evaluate the effect of exercise on the
      subsequent postexercise thresholds for vasoconstriction and shivering. On two
      separate days, with six subjects (3 women), a whole body water-perfused suit
      slowly decreased mean skin temperature (approximately 7.0 degreesC/h) until
      thresholds for vasoconstriction and shivering were clearly established. Subjects
      were then rewarmed by increasing water temperature until both esophageal and mean
      skin temperatures returned to near-baseline values. Subjects either performed 15
      min of cycle ergometry (65% maximal O2 consumption) followed by 30 min of
      recovery (Exercise) or remained seated with no exercise for 45 min (Control).
      Subjects were then cooled again. We mathematically compensated for changes in
      skin temperatures by using the established linear cutaneous contribution of skin
      to the control of vasoconstriction and shivering (20%). The calculated core
      temperature threshold (at a designated skin temperature of 30.0 degreesC) for
      vasoconstriction increased significantly from 36.64 +/- 0.20 to 36.89 +/- 0.22
      degreesC postexercise (P < 0.01). Similarly, the shivering threshold increased
      from 35.73 +/- 0.13 to 36.13 +/- 0.12 degreesC postexercise (P < 0.01). In
      contrast, sequential measurements, without exercise, demonstrate a time-dependent
      decrease in both the vasoconstriction (0.10 degreesC) and shivering (0.12
      degreesC) thresholds. These data indicate that exercise has a prolonged effect by
      increasing the postexercise thresholds for both cold thermoregulatory responses.

PMID- 9760329
TI  - Endothelial modulation of neural sympathetic vascular tone in canine skeletal
      muscle.
AB  - The effect of nitric oxide synthase (NOS) inhibition and endothelin-A (ETA)
      receptor blockade on neural sympathetic control of vascular tone in the
      gastrocnemius muscle was examined in anesthetized dogs under conditions of
      constant flow. Muscle perfusion pressure (MPP) was measured before and after NOS
      inhibition (Nomega-nitro-L-arginine methyl ester; L-NAME) and ETA-receptor
      blockade [cyclo-(D-Trp-d-Asp-Pro-D-Val-Leu); BQ-123]. Zero and maximum
      sympathetic nerve activities were achieved by sciatic nerve cold block and
      stimulation, respectively. In group 1 (n = 6), MPP was measured 1) before nerve
      cold block, 2) during nerve cold block, and 3) during nerve stimulation.
      Measurements under these conditions were repeated after L-NAME and then BQ-123.
      The same protocol was followed in group 2 (n = 6) except that the order of L-NAME
      and BQ-123 was reversed. MPP and muscle vascular resistance (MVR) increased after
      L-NAME and then decreased to control values after BQ-123. MVR decreased after BQ
      123 alone and, with the addition of L-NAME, increased to a level not different
      from that observed during the control period. MVR fell during nerve cold block.
      This response was not affected by administration of L-NAME followed by BQ-123,
      but it was attenuated by administration of BQ-123 before L-NAME. The constrictor
      response during sympathetic nerve stimulation was enhanced by L-NAME; no further
      effect was observed with BQ-123, nor was the response affected when BQ-123 was
      given first. These findings indicate that endothelin contributes to 1) basal
      vascular tone in skeletal muscle and 2) the increase in skeletal muscle vascular
      resistance after NOS inhibition. Finally, nitric oxide "buffers" the degree of
      constriction in skeletal muscle vasculature during maximal sympathetic
      stimulation.

PMID- 9760330
TI  - Effect of endurance training on cardiac morphology in Alaskan sled dogs.
AB  - The cardiac morphology of 77 conscious Alaskan sled dogs before and after 5 mo of
      endurance training (20 km/day team pulling a sled and musher) was studied using
      two-dimensional and M-mode echocardiography. Subgroups included dogs with at
      least one season of previous training ("veterans") and dogs undergoing their
      first season of training ("rookies"). Training resulted in a significant (P <
      0.05) decrease in resting heart rate (-15%) and significant increases in
      interventricular septal thickness (systole, 15%; diastole, 13%), left ventricular
      (LV) internal dimension in diastole (LVIDd, 4%), LV free wall thickness in
      systole (9%) and diastole (LVWd, 9%), and left atrial diameter (5%) in all dogs,
      but the increase in LVWd was greater in rookies (16%) than in veterans (7%).
      Training increased end-diastolic volume index (8%), LV mass index (24%), and
      heart weight index (24%) and decreased the LVIDd-to-LVWd ratio (-6%) but did not
      alter cardiac index. We conclude that increased LV mass attributable to LV
      dilation and hypertrophy is associated with endurance training in Alaskan sled
      dogs. Disproportionate LV wall thickening accompanying LV dilation suggests that
      cardiac morphological changes are due to volume and pressure loading. These
      training-induced changes are similar to those documented in human athletes
      undergoing combined isometric and isotonic training and differ from studies of
      dogs trained on treadmills.

PMID- 9760331
TI  - Scaling of submaximal oxygen uptake with body mass and combined mass during
      uphill treadmill bicycling.
AB  - This study examined the scaling relationships of net O2 uptake [V(O2)(net) =
      V(O2) - resting V(O2)] to body mass (MB) and combined mass (MC = MB + bicycle)
      during uphill treadmill bicycling. It was hypothesized that V(O2)(net) (l/min)
      would scale proportionally with MC [i.e., VO2(net) approximately M1.0C] and less
      than proportionally with MB [i.e., V(O2)(net) approximately MB]. Twenty-five
      competitive cyclists [73.9 +/- 8.8 and 85.0 +/- 9.0 (SD) kg for MB and MC,
      respectively] rode their bicycles on a treadmill at 3.46 m/s and grades of 1.7,
      3.5, 5.2, and 7.0% while V(O2) was measured. Multiple log-linear regression
      procedures were applied to the pooled V(O2)(net) data to determine the exponents
      for MC and MB after statistically controlling for differences in treadmill grade
      and dynamic friction. The regression models were highly significant (R2 = 0.95, P
      < 0.001). Exponents for MC (0.99, 95% confidence interval = 0.80-1.18) and MB
      (0.89, 95% confidence interval = 0.72-1. 07) did not differ significantly from
      each other or 1.0. It was concluded that the 0.99 MC exponent was due to
      gravitational resistance, whereas the MB exponent was <1.0 because the bicycles
      were relatively lighter for heavier cyclists.

PMID- 9760332
TI  - O2 uptake kinetics after acetazolamide administration during moderate- and heavy
      intensity exercise.
AB  - Inhibition of carbonic anhydrase (CA) is associated with a lower plasma lactate
      concentration ([La-]pl) during fatiguing exercise. We hypothesized that a lower
      [La-]pl may be associated with faster O2 uptake (V(O2)) kinetics during constant
      load exercise. Seven men performed cycle ergometer exercise during control (Con)
      and acute CA inhibition with acetazolamide (Acz, 10 mg/kg body wt iv). On 6
      separate days, each subject performed 6-min step transitions in work rate from 0
      to 100 W (below ventilatory threshold, <VE(T)) or to a V(O2) corresponding to
      approximately 50% of the difference between the work rate at VE(T) and peak V(O2)
      (>VE(T). Gas exchange was measured breath by breath. Trials were interpolated at
      1-s intervals and ensemble averaged to yield a single response. The mean response
      time (MRT, i.e., time to 63% of total exponential increase) for on- and off
      transients was determined using a two- (<VE(T)) or a three-component exponential
      model (>VE(T)). Arterialized venous blood was sampled from a dorsal hand vein and
      analyzed for [La-]pl. MRT was similar during Con (31.2 +/- 2.6 and 32.7 +/- 1.2 s
      for on and off, respectively) and Acz (30.9 +/- 3.0 and 31.4 +/- 1.5 s for on and
      off, respectively) for work rates <VE(T). At work rates >VE(T), MRT was similar
      between Con (69.1 +/- 6.1 and 50.4 +/- 3.5 s for on and off, respectively) and
      Acz (69.7 +/- 5.9 and 53.8 +/- 3.8 s for on and off, respectively). On- and off
      MRTs were slower for >VE(T) than for <VE(T) exercise. [La-]pl increased above 0-W
      cycling values during <VE(T) and >VE(T) exercise but was lower at the end of the
      transition during Acz (1.4 +/- 0.2 and 7.1 +/- 0.5 mmol/l for <VE(T) and >VE(T)
      respectively) than during Con (2.0 +/- 0.2 and 9.8 +/- 0.9 mmol/l for <VE(T) and
      >VE(T), respectively). CA inhibition does not affect O2 utilization at the onset
      of <VE(T) or >VE(T) exercise, suggesting that the contribution of oxidative
      phosphorylation to the energy demand is not affected by acute CA inhibition with
      Acz.

PMID- 9760333
TI  - Faster adjustment of O2 delivery does not affect V(O2) on-kinetics in isolated in
      situ canine muscle.
AB  - The mechanism(s) limiting muscle O2 uptake (VO2) kinetics was investigated in
      isolated canine gastrocnemius muscles (n = 7) during transitions from rest to 3
      min of electrically stimulated isometric tetanic contractions (200-ms trains, 50
      Hz; 1 contraction/2 s; 60-70% of peak V(O2)). Two conditions were mainly
      compared: 1) spontaneous adjustment of blood flow (Q) [control, spontaneous Q (C
      Spont)]; and 2) pump-perfused Q, adjusted approximately 15 s before contractions
      at a constant level corresponding to the steady-state value during contractions
      in C Spont [faster adjustment of O2 delivery (Fast O2 Delivery)]. During Fast O2
      Delivery, 1-2 ml/min of 10(-2) M adenosine were infused intra-arterially to
      prevent inordinate pressure increases with the elevated Q. The purpose of the
      study was to determine whether a faster adjustment of O2 delivery would affect
      V(O2) kinetics. Q was measured continuously; arterial (Ca(O2)) and popliteal
      venous (Cv(O2)) O2 contents were determined at rest and at 5- to 7-s intervals
      during contractions; O2 delivery was calculated as Q x Ca(O2), and V(O2) was
      calculated as Q x arteriovenous O2 content difference. Times to reach 63% of the
      difference between baseline and steady-state VO2 during contractions were 23.8 +/
      2.0 (SE) s in C Spont and 21.8 +/- 0.9 s in Fast O2 Delivery (not significant).
      In the present experimental model, elimination of any delay in O2 delivery during
      the rest-to-contraction transition did not affect muscle V(O2) kinetics, which
      suggests that this kinetics was mainly set by an intrinsic inertia of oxidative
      metabolism.

PMID- 9760334
TI  - Peripheral O2 diffusion does not affect V(O2)on-kinetics in isolated insitu
      canine muscle.
AB  - To test the hypothesis that muscle O2 uptake (V(O2)) on-kinetics is limited, at
      least in part, by peripheral O2 diffusion, we determined the V(O2) on-kinetics in
      1) normoxia (Control); 2) hyperoxic gas breathing (Hyperoxia); and 3) hyperoxia
      and the administration of a drug (RSR-13, Allos Therapeutics), which right-shifts
      the Hb-O2 dissociation curve (Hyperoxia+RSR-13). The study was conducted in
      isolated canine gastrocnemius muscles (n = 5) during transitions from rest to 3
      min of electrically stimulated isometric tetanic contractions (200-ms trains, 50
      Hz; 1 contraction/2 s; 60-70% peak V(O2)). In all conditions, before and during
      contractions, muscle was pump perfused with constantly elevated blood flow (Q),
      at a level measured at steady state during contractions in preliminary trials
      with spontaneous Q x Adenosine was infused intra-arterially to prevent inordinate
      pressure increases with the elevated Q x Q was measured continuously, arterial
      and popliteal venous O2 concentrations were determined at rest and at 5- to 7-s
      intervals during contractions, and V(O2) was calculated as Q x arteriovenous O2
      content difference. PO2 at 50% HbO2 saturation (P50) was calculated. Mean
      capillary PO2 (Pc(O2)) was estimated by numerical integration. P50 was higher in
      Hyperoxia+RSR-13 [40 +/- 1 (SE) Torr] than in Control and in Hyperoxia (31 +/- 1
      Torr). After 15 s of contractions, Pc(O2) was higher in Hyperoxia (97 +/- 9 Torr)
      vs. Control (53 +/- 3 Torr) and in Hyperoxia+RSR-13 (197 +/- 39 Torr) vs.
      Hyperoxia. The time to reach 63% of the difference between baseline and steady
      state V(O2) during contractions was 24.7 +/- 2.7 s in Control, 26.3 +/- 0.8 s in
      Hyperoxia, and 24.7 +/- 1.1 s in Hyperoxia+RSR-13 (not significant). Enhancement
      of peripheral O2 diffusion (obtained by increased PcO2 at constant O2 delivery)
      during the rest-to-contraction (60-70% of peak V(O2)) transition did not affect
      muscle V(O2) on- kinetics.

PMID- 9760335
TI  - Chemo- and baroresponses differ in African-Americans and Caucasians in sleep.
AB  - To determine sleep effects on baro- and ventilatory responses to transient chemo-
      and barostimulation in African-Americans and Caucasians, 26 nonobese normotensive
      young subjects (13 African-Americans and 13 Caucasians) were studied awake and in
      non-rapid-eye movement (NREM) and rapid-eye-movement sleep during induced
      transient hypoxemia (N2), hypertension (phenylephrine, PE), and concomitant
      hypoxemia and hypertension (N2 + PE). Arterial blood pressure was recorded by
      plethysmographic volume clamp, minute ventilation by pneumotachograph, and
      arterial O2 saturation by pulse oximeter. For all subjects, chronotropic
      baroresponse (Deltapulse interval/Deltasystolic blood pressure, where Delta is
      change) increased with NREM sleep (P = 0.007). Baroresponse slope was greater in
      Caucasians than in African-Americans (ANOVA, P = 0.02). Hypoxemic ventilatory
      response (Deltaminute ventilation/Deltaarterial O2 saturation) was greater in
      African-Americans than in Caucasians in NREM sleep (P = 0.01), as was hypoxemic
      attenuation of baroresponse (N2 + PE, P = 0.03). These data suggest sleep-related
      differences in arterial chemo- and baroreceptor responses in normal young African
      Americans and Caucasians, which may have implications concerning development of
      systemic hypertension.

PMID- 9760336
TI  - Effect of urokinase on disseminated intravascular coagulation.
AB  - Our study evaluated the possible therapeutic effect of urokinase in treating the
      microthrombiotic effects of disseminated intravascular coagulation by assisting
      the activation of endogenous plasminogen. Twenty-six pigs were anesthetized,
      intubated, mechanically ventilated, and surgically catheterized. Septic shock was
      induced in all 26 pigs by an intravenous infusion of heat-killed Escherichia
      coli. The pigs were divided into two sets of experiments: in experiment 2 (n =
      14), one-half received an intravenous dose of urokinase 1 h after heat-killed E.
      coli infusion and in experiment 3 (n = 12) one-half received an intravenous bolus
      dose and a continuous drip of urokinase 2 h after heat-killed E. coli infusion.
      The untreated pigs served as controls. Hemodynamic parameters, blood chemistries,
      and blood gases were analyzed. Urokinase given 1 h after bacterial toxin infusion
      significantly restored blood flow, resulting in an increase in cardiovascular and
      pulmonary function and improved survival rate (43% control vs. 100% treated, 24-h
      experimental period). Treatment given after 2 h showed some significant effect on
      pulmonary function; however, within 10 h of E. coli infusion, mortality rates in
      control and treated groups were 100 and 83%, respectively. Early administration
      of urokinase after onset of disseminated intravascular coagulation restored blood
      flow and helped resolve organ damage.

PMID- 9760337
TI  - Spaceflight and development of immune responses.
AB  - The NIH.R1 Space Shuttle experiment was designed to study the effects of
      spaceflight on rodent development. Pregnant rats were flown on the Space Shuttle
      for 11 days, and pregnant control rats were maintained in animal enclosure
      modules in a ground-based chamber under conditions approximating those in flight.
      Additional controls were in standard housing. The effects of the flight on
      immunological parameters of dams, fetuses, and pups were determined.
      Blastogenesis of spleen cells in response to mitogen was inhibited in flown dams
      but was not inhibited in cells from their pups. Interferon-gamma production by
      spleen cells showed a trend toward inhibition in flown dams but not in their
      pups. The response of bone marrow cells to colony-stimulating factor showed a
      trend toward inhibition after spaceflight in dams, but the response of fetus and
      pup liver cells was not inhibited. Total serum IgG was not affected by
      spaceflight. None of the examined immune parameters that were altered in rat dams
      after spaceflight was found to be altered in their offspring.

PMID- 9760338
TI  - Within-night variation in respiratory effort preceding apnea termination and EEG
      delta power in sleep apnea.
AB  - We studied the within-night variability of the maximum esophageal pressure
      deflection before apnea termination (DPmax) in nine patients with severe
      obstructive sleep apnea as an index of the arousal threshold and the mean
      electroencephalogram (EEG) delta power for each 30 s as an index of the timing of
      sleep cycles. Periodicity in the time variation of delta power and DPmax was
      analyzed by determining their power spectral density and their relationship
      determined by cross correlation. DPmax and delta power varied cyclically and in
      phase with a major periodicity (major peak in power spectral density) of 117.6 +/
      8.8 (SE) min. The correlation between the values of DPmax and delta power was
      significant (P < 0.001) in each subject (mean r = 0.47 +/- 0.03), and the
      coherence between DPmax and delta power at their dominant frequency was high.
      Within cycles of non-rapid-eye-movement sleep, DPmax and delta power increased,
      reaching peak values on average at or after midcycle. These findings suggest that
      the arousal threshold to airway occlusion in patients with obstructive sleep
      apnea varies cyclically during the night synchronous to the underlying cycles of
      sleep.

PMID- 9760339
TI  - Exercise-training-induced alterations in hepatic function in mares.
AB  - The effects of exercise training on hepatic function in horses were determined by
      studying the plasma clearance of antipyrine (20 mg/kg iv) in adult mares that
      either underwent treadmill training for 5 wk (n = 7) or remained in box stalls
      for the same time period (n = 6). Training consisted of treadmill exercise at 60%
      (12 min/day) and 90% (3 min/day) of pretraining maximal oxygen consumption
      (V(O2)max) for 6 days/wk for 5 wk. V(O2)max and velocity to obtain a blood
      lactate concentration of 4 mmol/l were significantly increased (from 129 to 149
      ml x min-1 x kg-1 and from 5.6 to 6.1 m/s, respectively) as a result of training.
      The plasma clearance and volume of distribution of antipyrine increased
      significantly in the trained group (from 5.5 to 6.4 ml x min-1 x kg-1 and from
      813 to 881 ml/kg, respectively) and decreased significantly in the untrained
      group. Elimination half-lives did not change as a result of training or box rest.
      Increases in plasma antipyrine clearance were indicative of an increase in
      hepatic metabolism of antipyrine. Increases in the volume of distribution of
      antipyrine suggest that total body water increases as a result of exercise
      training.

PMID- 9760340
TI  - Individual variation in response to altitude training.
AB  - Moderate-altitude living (2,500 m), combined with low-altitude training (1,250 m)
      (i.e., live high-train low), results in a significantly greater improvement in
      maximal O2 uptake (V(02)max) and performance over equivalent sea-level training.
      Although the mean improvement in group response with this "high-low" training
      model is clear, the individual response displays a wide variability. To determine
      the factors that contribute to this variability, 39 collegiate runners (27 men,
      12 women) were retrospectively divided into responders (n = 17) and nonresponders
      (n = 15) to altitude training on the basis of the change in sea-level 5,000-m run
      time determined before and after 28 days of living at moderate altitude and
      training at either low or moderate altitude. In addition, 22 elite runners were
      examined prospectively to confirm the significance of these factors in a separate
      population. In the retrospective analysis, responders displayed a significantly
      larger increase in erythropoietin (Epo) concentration after 30 h at altitude
      compared with nonresponders. After 14 days at altitude, Epo was still elevated in
      responders but was not significantly different from sea-level values in
      nonresponders. The Epo response led to a significant increase in total red cell
      volume and V(O2) max in responders; in contrast, nonresponders did not show a
      difference in total red cell volume or V(O2)max after altitude training.
      Nonresponders demonstrated a significant slowing of interval-training velocity at
      altitude and thus achieved a smaller O2 consumption during those intervals,
      compared with responders. The acute increases in Epo and V(O2)max were
      significantly higher in the prospective cohort of responders, compared with
      nonresponders, to altitude training. In conclusion, after a 28-day altitude
      training camp, a significant improvement in 5,000-m run performance is, in part,
      dependent on 1) living at a high enough altitude to achieve a large acute
      increase in Epo, sufficient to increase the total red cell volume and V(O2)max,
      and 2) training at a low enough altitude to maintain interval training velocity
      and O2 flux near sea-level values.

PMID- 9760341
TI  - Phosphocreatine hydrolysis during submaximal exercise: the effect of FIO2.
AB  - There is evidence that the concentration of the high-energy phosphate metabolites
      may be altered during steady-state submaximal exercise by the breathing of
      different fractions of inspired O2 (FIO2). Whereas it has been suggested that
      these changes may be the result of differences in time taken to achieve steady
      state O2 uptake (V(O2)) at different FIO2 values, we postulated that they are due
      to a direct effect of O2 tension. We used 31P-magnetic resonance spectroscopy
      during constant-load, steady-state submaximal exercise to determine 1) whether
      changes in high-energy phosphates do occur at the same V(O2) with varied FIO2 and
      2) that these changes are not due to differences in V(O2) onset kinetics. Six
      male subjects performed steady-state submaximal plantar flexion exercise [7.2 +/-
      0.6 (SE) W] for 10 min while lying supine in a 1.5-T clinical scanner. Magnetic
      resonance spectroscopy data were collected continuously for 2 min before
      exercise, 10 min during exercise, and 6 min during recovery. Subjects performed
      three different exercise bouts at constant load with the FIO2 switched after 5
      min of the 10-min exercise bout. The three exercise treatments were 1) FIO2 of
      0.1 switched to 0.21, 2) FIO2 of 0.1 switched to 1.00, and 3) FIO2 of 1.00
      switched to 0.1. For all three treatments, the FIO2 switch significantly (P </=
      0.05) altered phosphocreatine: 1) 55.5 +/- 4.8 to 67.8 +/- 4.9% (%rest); 2) 59.0
      +/- 4.3 to 72.3 +/- 5.1%; and 3) 72.6 +/- 3.1 to 64.2 +/- 3.4%, respectively.
      There were no significant differences in intracellular pH for the three
      treatments. The results demonstrate that the differences in phosphocreatine
      concentration with varied FIO2 are not the result of different V(O2) onset
      kinetics, as this was eliminated by the experimental design. These data also
      demonstrate that changes in intracellular oxygenation, at the same work
      intensity, result in significant changes in cell homeostasis and thereby suggest
      a role for metabolic control by O2 even during submaximal exercise.

PMID- 9760342
TI  - Effect of time-varying load on degree of bronchoconstriction in the dog.
AB  - It is well established that the degree of airway smooth muscle shortening
      produced by a given dose of bronchial agonist is greatly affected by lung volume.
      The airways are tethered by parenchymal attachments, the tension of which
      increases progressively with lung volume, thereby presenting a commensurately
      increasing hindrance to smooth muscle contraction. Earlier studies (P. F. Dillon,
      M. O. Aksoy, S. P. Driska, and R. A. Murphy. Science 211: 495-497, 1981)
      presented evidence that smooth muscle contraction initially involves rapidly
      cycling cross bridges, which then change to noncycling (latch) bridges. They also
      suggested that most of the muscle shortening occurs during the early rapid cross
      bridge phase. This implies that smooth muscle subject to a given load early in
      contraction should shorten less than when it is subject to the same load later
      on. An in vitro study (W. Li and N. L. Stephens. Can. J. Physiol. Pharmacol. 72:
      1458-1463, 1994) obtained support for this notion. To test this hypothesis in
      vivo, we measured the changes in lung impedance at 1 and 6 Hz produced in dogs by
      a bolus intravenous injection of methacholine when lung volume was increased for
      10 s at different times after injection. We found that the changes in mechanics
      were greatly inhibited, whereas lung volume was elevated. However, when lung
      volume was returned to its initial level, the lung mechanics continued to change
      at a rate unaffected by the preceding volume change. We conclude that temporary
      mechanical inhibition of airway smooth muscle shortening in the normal dog in
      vivo merely delays an otherwise normal course of contraction.

PMID- 9760344
TI  - Magnitude and time course of hemodynamic responses to Mueller maneuvers in
      patients with congestive heart failure.
AB  - To simulate the immediate hemodynamic effect of negative intrathoracic pressure
      during obstructive apneas in congestive heart failure (CHF), without inducing
      confounding factors such as hypoxia and arousals from sleep, eight awake patients
      performed, at random, 15-s Mueller maneuvers (MM) at target intrathoracic
      pressures of -20 (MM -20) and -40 cmH2O (MM -40), confirmed by esophageal
      pressure, and 15-s breath holds, as apneic time controls. Compared with quiet
      breathing, at baseline, before these interventions, the immediate effects [first
      5 cardiac cycles (SD), P values refer to MM -40 compared with breath holds] of
      apnea, MM -20, and MM -40 were, for left ventricular (LV) systolic transmural
      pressure (Ptm), 1.0 +/- 1. 9, 7.2 +/- 3.5, and 11.3 +/- 6.8 mmHg (P < 0.01); for
      systolic blood pressure (SBP), 2.9 +/- 2.6, -5.5 +/- 3.4, and -12.1 +/- 6.8 mmHg
      (P < 0.01); and for stroke volume (SV) index, 0.4 +/- 2.8, -4.1 +/- 2.8, and -6.9
      +/- 2.3 ml/m2 (P < 0.001), respectively. Corresponding values over the last five
      cardiac cycles were for LVPtm 6.4 +/- 4.4, 5.4 +/- 6.6, and -4.5 +/- 9.1 mmHg (P
      < 0.01); for SBP 6.9 +/- 4.2, -8.2 +/- 7.7, and -24.2 +/- 6.9 mmHg (P < 0.01);
      and for SV index -0. 4 +/- 2.1, -5.2 +/- 2.8, and -9.2 +/- 4.8 ml/m2 (P < 0.001),
      respectively. Thus, in CHF patients, the initial hemodynamic response to the
      generation of negative intrathoracic pressure includes an immediate increase in
      LV afterload and an abrupt fall in SV. The magnitude of response is proportional
      to the intensity of the MM stimulus. By the end of a 15-s MM -40, LVPtm falls
      below baseline values, yet SV and SBP do not recover. Thus, when -40 cmH2O
      intrathoracic pressure is sustained, additional mechanisms, such as a drop in LV
      preload due to ventricular interaction, are engaged, further reducing SV. The net
      effect of MM -40 was a 33% reduction in SV index (from 27 to 18 ml/min2), and a
      21% reduction in SBP (from 121 to 96 mmHg). Obstructive apneas can have adverse
      effects on systemic and, possibly, coronary perfusion in CHF through dynamic
      mechanisms that are both stimulus and time dependent.

PMID- 9760343
TI  - Leg mass and lower body negative pressure tolerance in men and women.
AB  - To explore the hypothesis that lower body muscle mass correlates with orthostatic
      tolerance, 18 healthy volunteers (age 18-48 yr; 10 men, 8 women) underwent a
      graded lower body negative pressure (LBNP) protocol consisting of six, 5-min
      stages of suction up to 60 mmHg in 10-mmHg increments. Forearm blood flow, heart
      rate, and blood pressure were measured, and forearm vascular resistance was
      calculated. Leg muscle mass was assessed by dual-energy X-ray absorptiometry. All
      subjects received standard intravenous hydration for at least 8 h before the
      study. Six men and four women completed all stages of LBNP. Four men and four
      women developed presyncopal symptoms, including marked bradycardia and/or
      hypotension, at LBNP levels of 30 mmHg (n = 2;1 man, 1 woman), 40 mmHg (n = 2;1
      man, 1 woman), and 50 mmHg (n = 4;2 men, 2 women). The presyncopal subjects had
      leg muscle masses ranging from 19.5 to 25.2 kg in men and from 11.7 to 16.6 kg in
      women. In subjects who completed all stages of LBNP, leg muscle mass ranged from
      17.5 to 24.1 kg in men and from 10.4 to 18.0 kg in women. Leg muscle mass did not
      differ between presyncopal subjects and those who completed the protocol.
      Furthermore, there were no differences in the hemodynamic responses to LBNP
      between subjects with low vs. high leg mass. These data suggest that leg muscle
      mass is not a critical determinant of LBNP tolerance in otherwise healthy men and
      women.

PMID- 9760345
TI  - Stimulation of breathing by activation of pulmonary peripheral afferents in
      rabbits.
AB  - Respiratory response to selective activation of vagal afferents in the peripheral
      airways was investigated in anesthetized, open-chest, and artificially ventilated
      rabbits. Phrenic activity was used as an index of central respiratory drive
      before and after injection of hypertonic saline (8.1%, 0.1 ml) into the periphery
      of the lung to stimulate the afferents. The amplitude of "integrated" phrenic
      activity and phrenic burst rate increased by 19 +/- 3.4 and 53.7 +/- 12.7% (n =
      23; P < 0.001), respectively. The response peaked at 5.5 +/- 1.6 s and returned
      to the baseline at 7 min (median) after the injection. The magnitude of the
      response was positively related to the concentration of injected NaCl. The
      response could not be elicited by injection of normal saline and was abolished by
      vagotomy. Because artificial ventilation caused phrenic activity to be entrained
      with the ventilator, respiratory drive was further assessed after the ventilator
      was stopped. Again, neural hyperpnea and tachypnea were observed. Because
      activation of a small fraction of the pulmonary peripheral afferents resulted in
      vigorous stimulation of respiratory drive, we speculate that initiation of this
      reflex may contribute to hyperpnea and tachypnea under both physiological and
      pathophysiological conditions.

PMID- 9760346
TI  - Effect of caffeine on metabolism, exercise endurance, and catecholamine responses
      after withdrawal.
AB  - In this study the effects of acute caffeine ingestion on exercise performance,
      hormonal (epinephrine, norepinephrine, insulin), and metabolic (free fatty acids,
      glycerol, glucose, lactate, expired gases) parameters during short-term
      withdrawal from dietary caffeine were investigated. Recreational athletes who
      were habitual caffeine users (n = 6) (maximum oxygen uptake 54.5 +/- 3.3 ml x kg
      1 x min-1 and daily caffeine intake 761.3 +/- 11.8 mg/day) were tested under
      conditions of no withdrawal and 2-day and 4-day withdrawal from dietary caffeine.
      There were seven trials in total with a minimum of 10 days between trials. On the
      day of the exercise trial, subjects ingested either dextrose placebo or 6 mg/kg
      caffeine in capsule form 1 h before cycle ergometry to exhaustion at 80-85% of
      maximum oxygen uptake. Test substances were assigned in a random, double-blind
      manner. A final placebo control trial completed the experiment. There was no
      significant difference in any measured parameters among days of withdrawal after
      ingestion of placebo. At exhaustion in the 2- and 4-day withdrawal trials, there
      were significant increases in plasma norepinephrine in response to caffeine
      ingestion. Caffeine-induced increases in serum free fatty acids occurred after 4
      days and only at rest. Subjects responded to caffeine with increases in plasma
      epinephrine (P < 0.05) at exhaustion and prolonged exercise time in all caffeine
      trials compared with placebo, regardless of withdrawal from caffeine. It is
      concluded that increased endurance is unrelated to hormonal or metabolic changes
      and that it is not related to prior caffeine habituation in recreational
      athletes.

PMID- 9760347
TI  - Caffeine, performance, and metabolism during repeated Wingate exercise tests.
AB  - Investigations examining the ergogenic and metabolic influence of caffeine during
      short-term high-intensity exercise are few in number and have produced
      inconsistent results. This study examined the effects of caffeine on repeated
      bouts of high-intensity exercise in recreationally active men. Subjects (n = 9)
      completed four 30-s Wingate (WG) sprints with 4 min of rest between each exercise
      bout on two separate occasions. One hour before exercise, either placebo (P1;
      dextrose) or caffeine (Caf; 6 mg/kg) capsules were ingested. Caf ingestion did
      not have any effect on power output (peak or average) in the first two WG tests
      and had a negative effect in the latter two exercise bouts. Plasma epinephrine
      concentration was significantly increased 60 min after Caf ingestion compared
      with P1; however, this treatment effect disappeared once exercise began. Caf
      ingestion had no significant effect on blood lactate, O2 consumption, or aerobic
      contribution at any time during the protocol. After the second Wingate test,
      plasma NH3 concentration increased significantly from the previous WG test and
      was significantly higher in the Caf trial compared with P1. These data
      demonstrate no ergogenic effect of caffeine on power output during repeated bouts
      of short-term, intense exercise. Furthermore, there was no indication of
      increased anaerobic metabolism after Caf ingestion with the exception of an
      increase in NH3 concentration.

PMID- 9760348
TI  - Ozone enhances excitabilities of pulmonary C fibers to chemical and mechanical
      stimuli in anesthetized rats.
AB  - Acute exposure to ozone (O3) enhances pulmonary chemoreflex response to
      capsaicin, and an increased sensitivity of bronchopulmonary C-fiber afferent
      endings may be involved. The present study was aimed at determining the effect of
      O3 on the responses of pulmonary C fibers to chemical and mechanical stimuli. A
      total of 31 C fibers were studied in anesthetized, open-chest, and vagotomized
      rats. During control, right atrial injection of a low dose of capsaicin abruptly
      evoked a short and mild burst of discharge [0.77 +/- 0.28 impulses (imp)/s, 2-s
      average]. After acute exposure to O3 (3 parts/million for 30 min), there was no
      significant change in arterial blood pressure, tracheal pressure, or baseline
      activity of C fibers. However, the stimulatory effect of the same dose of
      capsaicin on these fibers was markedly enhanced (6.05 +/- 0.88 impulses/s; P <
      0.01) and prolonged immediately after O3 exposure, and returned toward control in
      54 +/- 6 min. Similarly, the pulmonary C-fiber response to injection of a low
      dose of lactic acid was also elevated after O3 exposure. Furthermore, O3 exposure
      significantly potentiated the C-fiber response to constant-pressure (tracheal
      pressure = 30 cmH2O) lung inflation (control: 0.19 +/- 0.07 imp/s; after O3: 1.12
      +/- 0.26 imp/s; P < 0.01). In summary, these results show that the excitabilities
      of pulmonary C-fiber afferents to lung inflation and injections of chemical
      stimulants are markedly potentiated after acute exposure to O3, suggesting a
      possible involvement of these afferents in the O3-induced changes in breathing
      pattern and chest discomfort in humans.

PMID- 9760349
TI  - Effect of exercise timing on postprandial lipemia and HDL cholesterol
      subfractions.
AB  - The purpose of the study was to examine the effect of exercise timing on
      postprandial lipemia responses. Subjects were 21 recreationally trained men (ages
      27 +/- 1.7 yr). Each subject performed four trials: 1) Control (fat meal only),
      2) Post (exercise 1 h after a fat meal), 3) 1 h-Pre (exercise 1 h before a fat
      meal), and 4) 12 h-Pre (exercise 12 h before a fat meal). In each trial, subjects
      had a standard fat meal to induce postprandial hypertriglyceridemia. Blood
      samples were taken at 0 h (immediately before the fat meal) and at 2, 4, 6, 8,
      and 24 h after the meal. In the exercise trials, each subject exercised at 60% of
      maximal O2 consumption for 1 h. The results indicated that triglyceride area
      under the curve scores in premeal-exercise trials were lower (P < 0. 05) than
      those in Post and Control. At 24 h, total high-density lipoprotein (HDL)
      cholesterol in the premeal-exercise trials was higher (P < 0.05) than that at 0
      h, whereas total HDL-cholesterol was not changed in Control and Post. At 24 h,
      HDL subtype 2-cholesterol was higher (P < 0.05) in the premeal-exercise trials
      than in Control, which did not differ from Post. These results suggest that
      exercising before a fat meal may have a beneficial effect on the triglyceride
      response and HDL metabolism, which may blunt atherosclerotic process induced by
      the fat meal.

PMID- 9760350
TI  - Effect of prolonged, heavy exercise on pulmonary gas exchange in athletes.
AB  - During maximal exercise, ventilation-perfusion inequality increases, especially
      in athletes. The mechanism remains speculative. We hypothesized that, if
      interstitial pulmonary edema is involved, prolonged exercise would result in
      increasing ventilation-perfusion inequality over time by exposing the pulmonary
      vascular bed to high pressures for a long duration. The response to short-term
      exercise was first characterized in six male athletes [maximal O2 uptake
      (V(O2)max) = 63 ml x kg-1 x min-1] by using 5 min of cycling exercise at 30, 65,
      and 90% V(O2) max. Multiple inert-gas, blood-gas, hemodynamic, metabolic rate,
      and ventilatory data were obtained. Resting log SD of the perfusion distribution
      (log SDQ) was normal [0.50 +/- 0.03 (SE)] and increased with exercise (log SDQ =
      0.65 +/- 0.04, P < 0.005), alveolar-arterial O2 difference increased (to 24 +/- 3
      Torr), and end-capillary pulmonary diffusion limitation occurred at 90% V(O2)max.
      The subjects recovered for 30 min, then, after resting measurements were taken,
      exercised for 60 min at approximately 65% V(O2)max. O2 uptake, ventilation,
      cardiac output, and alveolar-arterial O2 difference were unchanged after the
      first 5 min of this test, but log SDQ increased from 0.59 +/- 0.03 at 5 min to 0.
      66 +/- 0.05 at 60 min (P < 0.05), without pulmonary diffusion limitation. Log SDQ
      was negatively related to total lung capacity normalized for body surface area (r
      = -0.97, P < 0.005 at 60 min). These data are compatible with interstitial edema
      as a mechanism and suggest that lung size is an important determinant of the
      efficiency of gas exchange during exercise.

PMID- 9760351
TI  - Dynamics of lung collapse and recruitment during prolonged breathing in porcine
      lung injury.
AB  - Oleic acid (OA) injection, lung lavage, and endotoxin infusion are three commonly
      used methods to induce experimental lung injury. The dynamics of lung collapse
      and recruitment in these models have not been studied, although knowledge of this
      is desirable to establish ventilatory techniques that keep the lungs open. We
      measured lung density by computed tomography during breath-holding procedures.
      Lung injury was induced with OA, lung lavage, or endotoxin in groups of six
      mechanically ventilated pigs. After a stabilization period, repetitive computed
      tomography scans of the same slice were obtained during prolonged expirations
      with and without positive end-expiratory pressure and during prolonged
      inspirations after 5 and 30 s of expiration. Lung collapse and recruitment
      occurred mainly within the first 4 s of breath-holding procedures in all three
      lung injury models, and some collapse and recruitment occurred even within 0.6 s.
      OA-injured lungs were significantly more unstable than lungs injured by
      bronchoalveolar lavage or endotoxin infusion. In this experimental setting,
      expiration times <0.6 s are required to avoid cyclic alveolar collapse during
      mechanical ventilation without extrinsic positive end-expiratory pressure.

PMID- 9760352
TI  - Hormonal responses to consecutive days of heavy-resistance exercise with or
      without nutritional supplementation.
AB  - Nine resistance-trained men consumed either a protein-carbohydrate supplement or
      placebo for 1 wk in a crossover design separated by 7 days. The last 3 days of
      each treatment, subjects performed resistance exercise. The supplement was
      consumed 2 h before and immediately after the workout, and blood was obtained
      before and after exercise (0, 15, 30, 45, and 60 min postexercise). Lactate,
      growth hormone, and testosterone were significantly (P </= 0.05) elevated
      immediately postexercise. The lactate response was significantly lower during
      supplementation on days 2 and 3. Growth hormone and prolactin responses on day 1
      were significantly higher during supplementation. After exercise, testosterone
      declined below resting values during supplementation. Cortisol decreased
      immediately postexercise on day 1; the response was diminished on days 2 and 3.
      Glucose and insulin were significantly elevated by 30 min during supplementation
      and remained stable during placebo. Insulin-like growth factor-I was higher
      during supplementation on days 2 and 3. These data indicate that protein
      carbohydrate supplementation before and after training can alter the metabolic
      and hormonal responses to consecutive days of heavy-resistance exercise.

PMID- 9760353
TI  - Effects of prior exercise on exercise-induced arterial hypoxemia in young women.
AB  - Twenty-eight healthy women (ages 27.2 +/- 6.4 yr) with widely varying fitness
      levels [maximal O2 consumption (VO2 max), 31-70 ml . kg-1 . min-1] first
      completed a progressive incremental treadmill test to VO2 max (total duration,
      13.3 +/- 1.4 min; 97 +/- 37 s at maximal workload), rested for 20 min, and then
      completed a constant-load treadmill test at maximal workload (total duration, 143
      +/- 31 s). At the termination of the progressive test, 6 subjects had maintained
      arterial PO2 (PaO2) near resting levels, whereas 22 subjects showed a >10 Torr
      decrease in PaO2 [78.0 +/- 7.2 Torr, arterial O2 saturation (SaO2), 91.6 +/-
      2.4%], and alveolar-arterial O2 difference (A-aDO2, 39.2 +/- 7.4 Torr). During
      the subsequent constant-load test, all subjects, regardless of their degree of
      exercise-induced arterial hypoxemia (EIAH) during the progressive test, showed a
      nearly identical effect of a narrowed A-aDO2 (-4.8 +/- 3.8 Torr) and an increase
      in PaO2 (+5.9 +/- 4.3 Torr) and SaO2 (+1.6 +/- 1.7%) compared with at the end
      point of the progressive test. Therefore, EIAH during maximal exercise was
      lessened, not enhanced, by prior exercise, consistent with the hypothesis that
      EIAH is not caused by a mechanism which persists after the initial exercise
      period and is aggravated by subsequent exercise, as might be expected of exercise
      induced structural alterations at the alveolar-capillary interface. Rather, these
      findings in habitually active young women point to a functionally based mechanism
      for EIAH that is present only during the exercise period.

PMID- 9760354
TI  - Size constraints of telemeters in rats.
AB  - This study was designed to determine the maximum-size subcutaneous telemeter that
      would enable long-term and multichannel data collection in a 170-g rat for 90
      days. In phase 1, rats with implants weighing 5 (2.5 cm3), 15 (7.5 cm3), 25 (12.5
      cm3), 35 (17.5 cm3), or 45 (22.5 cm3) g were compared with sham-operated (SOC)
      and nonoperated (NOC) control animals. Severe skin lesions, seromas, and lower
      growth rates were observed in rats having implants >/=35 g. Thus, in phase 2,
      rats implanted with 23.5 g (17.5 cm3; 11-g active telemeter and 12.5-g implant)
      were compared with rats implanted with 11 g (6 cm3; telemeter only) and with the
      SOC and NOC groups. No differences were found among implanted groups in mean
      arterial pressure (MAP), heart rate (HR), subcutaneous temperature, or
      spontaneous activity under standard housing conditions. All groups were more
      active and had a higher MAP during the dark than the light phase of the daily
      cycle. During 2 h of cold exposure (3 degreesC), both telemetered groups
      exhibited similar changes in HR, MAP, temperature, and activity levels. Adrenal
      glands were larger in the 23.5-g group (51 +/- 1.6 mg) than in the SOC (46 +/-
      1.0 mg) and the NOC groups (41 +/- 2.0 mg). No other significant differences were
      found in organ, muscle, or bone weights. These data verify the feasibility of
      using 23.5-g (17.5 cm3) subcutaneous telemeters for chronic recordings in young
      adult rats.

PMID- 9760356
TI  - Determining bone and total body mineral content from body density and
      bioelectrical response spectroscopy.
AB  - We hypothesized that one could assess total body mineral (TBM) and bone mineral
      content (BMC) from measurements of body density and bioelectrical response
      spectroscopy (BRS)-determined total body water by using a three-compartment (3C)
      model. We compared TBM and BMC computed from measurements of water (2H2O dilution
      or BRS) and body density (underwater weighing) with [4-compartment (4C)] and
      without (3C) mineral (dual X-ray absorptiometry) in 15 women and 16 men. BRS used
      multifrequency or single-frequency estimates of water. Mean differences between
      the 3C and 4C models ranged from -6.1 to 2.2%. Correlations between models were
      0.82-0.91. Standard errors of the estimate of 8.5-9.3% were within the range of
      those previously reported, i.e., 4.9-13%. Use of BRS did not significantly
      decrease the strength of the correlations between the models. A significant mean
      difference (only in women) was found only with 3C single-frequency BRS estimates
      of TBM and BMC. We concluded that investigators can assess TBM and BMC 3C
      multifrequency BRS estimates in men and women.

PMID- 9760355
TI  - Time course of active and passive liquid and solute movement in the isolated
      perfused rat lung model.
AB  - The isolated perfused rat lung model (IL) is used to study alveolar epithelial
      transport properties. Most of the previous studies have been done over a short
      period of time and have not used the same preparation as a control and
      intervention group. We evaluated whether the IL preparation could be used for a
      prolonged period of time (5 h) and studied the rates of active Na+ transport,
      lung liquid clearance, and passive movement of solutes. Active Na+ transport and
      lung liquid clearance were stable from 1 to 5 h. The passive movement of small
      solutes (Na+, mannitol) did not change significantly, and albumin movement
      increased slightly at the fifth hour. Total RNA isolated from IL after 5 h was
      intact, and the Na+-K+-ATPase activity in alveolar type II cells isolated at the
      end of 5-h experiments was equal to Na+-K+-ATPase function from freshly isolated
      alveolar type II cells. Finally, we measured the stimulatory effect of the beta
      adrenergic-agonist terbutaline and the inhibitory effect of the Na+-K+-ATPase
      antagonist ouabain by using the same animal as a control. Accordingly, the
      isolated perfused lung model is functionally stable for at least 5 h, and it
      could be utilized to evaluate the effect of different interventions by using the
      same preparation.

PMID- 9760357
TI  - Effects of hindlimb contraction on pressor and muscle interstitial metabolite
      responses in the cat.
AB  - We used the microdialysis technique to measure the interstitial concentration of
      several putative metabolic stimulants of the exercise pressor reflex during 3-
      and 5-Hz twitch contractions in the decerebrate cat. The peak increases in heart
      rate and mean arterial pressure during contraction were 20 +/- 5 beats/min and 21
      +/- 8 mmHg and 27 +/- 9 beats/min and 37 +/- 12 mmHg for the 3- and 5-Hz
      stimulation protocols, respectively. All variables returned to baseline after 10
      min of recovery. Interstitial lactate rose (P < 0. 05) by 0.41 +/- 0.15 and 0.56
      +/- 0.16 mM for the 3- and 5-Hz stimulation protocols, respectively, and were not
      statistically different from one another. Interstitial lactate levels remained
      above (P < 0.05) baseline during recovery in the 5-Hz group. Dialysate phosphate
      concentrations (corrected for shifts in probe recovery) rose with stimulation (P
      < 0.05) by 0.19 +/- 0.08 and 0.11 +/- 0.03 mM for the 3- and 5-Hz protocols.
      There were no differences between groups. The resting dialysate K+ concentrations
      for the 3- and 5-Hz conditions were 4.0 +/- 0.1 and 3.9 +/- 0.1 meq/l,
      respectively. During stimulation the dialysate K+ concentrations rose steadily
      for both conditions, and the increase from rest to stimulation (P < 0.05) was
      0.57 +/- 0.19 and 0.81 +/- 0.06 meq/l for the 3- and 5-Hz conditions,
      respectively, with no differences between groups. Resting dialysate pH was 6.915
      +/- 0.055 and 6.981 +/- 0.032 and rose to 7.013 (P < 0.05) and 7.053 (P < 0.05)
      for the 3- and 5-Hz conditions, respectively, and then became acidotic (6. 905, P
      < 0.05) during recovery (5 Hz only). This study represents the first time
      simultaneous measurements of multiple skeletal muscle interstitial metabolites
      and pressor responses to twitch contractions have been made in the cat. These
      data suggest that interstitial K+ and phosphate, but not lactate and H+, may
      contribute to the stimulation of thin fiber muscle afferents during contraction.

PMID- 9760358
TI  - Clinical evaluation of two desensitizing agents for use under Class 5 silver
      amalgam restorations.
AB  - STATEMENT OF PROBLEM: Postoperative sensitivity is sometimes reported to be a
      clinical problem after placement of silver amalgam restorations. PURPOSE: This
      study compared postoperative sensitivity of Class 5 caries restored with amalgam
      restorations and Copalite or DentinBloc cavity liners. MATERIAL AND METHODS: At
      least 1 pair of amalgam restorations were placed in each of 16 patients and
      tested for sensitivity at 5 time periods. RESULTS: Sensitivity was significantly
      less with DentinBloc cavity liner (P < .05) at 24 hours, and 2 and 4 weeks. There
      was a directional but nonsignificant effect (P > .05) in favor of DentinBloc
      cavity liner at 1 and 16 weeks. CONCLUSION: DentinBloc cavity liner was more
      effective than Copalite cavity liner in reducing sort term postoperative
      sensitivity for amalgam restorations.

PMID- 9760359
TI  - Necessity of bevels for box only Class II composite restorations.
AB  - STATEMENT OF PROBLEM: The tooth preparation of a bevel is recommended to improve
      marginal quality of a composite restoration. However, in small Class II
      restorations, it is unclear if a bevel also contributed to a better marginal fit.
      PURPOSE: This study investigated the influence of tooth preparation design on
      microleakage of minimal posterior Class II composite restorations. MATERIAL AND
      METHODS: Box-shaped Class II tooth preparations for posterior composite
      restorations in maxillary premolars were restored with a total etch technique.
      The tooth preparations were beveled or non-beveled and the box prepared at a
      right angle cervically or additionally excavated. The facial and lingual box
      margins were also either beveled or unbeveled. The teeth were thermocycled and
      immersed in a dye solution. After sectioning specimens, dye penetration at the
      facial and palatal margins was recorded. RESULTS: A bevel-reduced microleakage
      both at the cervical and ascending walls. Enamel cracks were observed along
      certain unbeveled margins as recorded in this study. The additional excavation
      did not contribute to reduction of microleakage. CONCLUSIONS: Tooth preparation
      of a bevel is recommended for an optimal marginal seal in small box-type Class II
      composite restorations.

PMID- 9760360
TI  - Dental luting agents: A review of the current literature.
AB  - STATEMENT OF PROBLEM: The practice of fixed prosthodontic has changed
      dramatically with the introduction of innovative techniques and materials.
      Adhesive resin systems are examples of these changes that have led to the
      popularity of bonded ceramics and resin-retained fixed partial dentures. Today's
      dentist has the choice of a water-based luting agent (zinc phosphate, zinc
      polycarboxylate, glass ionomer, or reinforced zinc oxide-eugenol) or a resin
      system with or without an adhesive. Recent formulations of glass ionomer luting
      agents include resin components (resin-modified glass ionomers), which are
      increasingly popular in clinical practice. PURPOSE: This review summarizes the
      research on these systems with the goal of providing information that will help
      the reader choose the most suitable material. MATERIAL: The scientific studies
      have been evaluated in relation to the following categories: (1)
      biocompatibility, (2) caries or plaque inhibition, (3) microleakage, (4) strength
      and other mechanical properties, (5) solubility, (6) water sorption, (7)
      adhesion, (8) setting stresses, (9) wear resistance, (10) color stability, (11)
      radiopacity, (12) film thickness or viscosity, and (13) working and setting
      times. In addition, guidelines on luting-agent manipulation are related to
      available literature and include: (1) temporary cement removal, (2) smear layer
      removal, (3) powder/liquid ratio, (4) mixing temperature and speed, (5) seating
      force and vibration, and (6) moisture control. Tables of available products and
      their properties are also presented together with current recommendations by the
      authors with a rationale.

PMID- 9760361
TI  - A simple method of increasing the adhesion between resinous cements and tinplated
      gold alloys: a pilot study.
AB  - PURPOSE: This study: (1) tested 2 BIS-GMA resinous cements on tinplated gold
      alloy surfaces with shearing forces to record their bond strengths, and (2)
      determined whether storage of the tinplated surfaces in water before cementation
      affected initial bond strengths. MATERIAL AND METHODS: The bond strengths of
      Panavia Ex and Panavia 21 resinous cements to tinplated Type III gold alloy were
      measured when subjected to shearing forces. Specimens were luted in pairs with
      these cements. In one group, the cementation was performed after tinplating
      procedures. In the other group, tinplated alloy surfaces were first stored in
      water at 37 degrees C for 48 hours before cementation. RESULTS: A 3-fold increase
      in bond strength values was recorded for tinplated specimens stored in water
      before cementation with both cements, these differences were statistically
      significant. Storage of the specimen in water before cementation appeared to
      increase resistance of the alloy resin bond to failure with application of
      shearing forces. CONCLUSION: This pilot study suggested that it would be
      advantageous to age tinplated gold alloy surfaces in water for 48 hours before
      cementation.

PMID- 9760362
TI  - Shear bond strength of a titanium reinforced core material after using multistep
      and single-step bonding agents.
AB  - STATEMENT OF PROBLEM: Recently introduced single-step bonding agents reduce the
      number of steps involved in the bonding process. Nevertheless, there are few
      studies on the bond strengths obtained with these new systems. PURPOSE: This in
      vitro study evaluated the shear bond strength of a titanium-reinforced cores
      bonded with 5 multistep bonding systems (ScotchBond Multi-Purpose, OptiBond, All
      Bond-2, Tenure, and ProBond) and 5 single-step bonding systems (Single-Bond,
      OptiBond Solo, One-Step, Tenure Quik, and Prime & Bond 2.1). MATERIAL AND
      METHODS: The experiment was divided into 10 groups with 10 specimens per group.
      The shear bond strengths were evaluated after 24 hours on an MTS universal
      testing machine with a crosshead speed of 6.35 mm/minute. RESULTS: A 2-way ANOVA
      showed that All Bond-2 and One-Step recorded the highest means and differed
      significantly from the Den-Mat systems (Tenure A&B and Tenure Quik), the Kerr
      systems (OptiBond and Opti-Solo), and the Caulk systems (ProBond and Prime & Bond
      2.1). ProBond and Prime & Bond 2.1 bonding systems had the lowest mean and
      differed from the 3 other brands. Tenure A&B and Tenure Quik bonding systems and
      OptiBond and Opti-Solo bonding systems did not differ from one another.
      CONCLUSION: The single-step bonding agents did not produce an improvement in
      shear bond strengths. The wide range of shear bond strength reported for the
      single-step systems appeared to indicate that these bonding systems are technique
      sensitive.

PMID- 9760363
TI  - Development and clinical applications of a light-polymerized fiber-reinforced
      composite.
AB  - STATEMENT OF PROBLEM: After 0 years of intermittent reports in the literature,
      the use of fiber reinforcement is just now experiencing rapid expansion in
      dentistry. PURPOSE: This article describes the development and use of a
      continuous, unidirectional fiber reinforced composite as a framework for the
      fabrication of fixed prostheses. METHODS: By using various matrix materials and
      fibers, a number of fiber-reinforced composite formulations were evaluated with
      the goal of creating a system with optimized mechanical properties and handling
      characteristics. Fiber-reinforced composite based on a light polymerized BIS-GMA
      matrix has been used clinically to make 2-phase prostheses comprised of an
      internal glass fiber-reinforced composite substructure covered by a particulate
      composite. The clinical and laboratory procedures required for the fabrication
      and use of reinforced composite fixed prostheses are described for laboratory
      fabricated complete or partial coverage fixed prosthesis and chairside
      prosthesis. RESULTS: Although additional clinical experience is needed, fiber
      reinforced composite materials can be used to make metal-free prostheses with
      excellent esthetic qualities.

PMID- 9760364
TI  - Thickness of the remaining enamel after the preparation of cingulum rest seats on
      maxillary canines.
AB  - PURPOSE: This study evaluated the level of tissue removal that takes place on
      enamel and dentin during cingulum rest seat preparation. MATERIAL AND METHODS: A
      quantitative evaluation of the thickness of the remaining enamel of cingulum seat
      preparations to receive removable partial denture rests was carried out in 20
      maxillary canines with a light optical microscope. RESULTS: Thirty percent of the
      preparations were overextended into dentinal tissue, and 85% had depths that were
      insufficient to receive rests.

PMID- 9760365
TI  - Retention of prefabricated attachments for implant stabilized overdentures in the
      edentulous mandible: an in vitro study.
AB  - STATEMENT OF PROBLEM: Bar and stud attachments are widely used to stabilize
      overdentures on implants in the mandible. There is strong evidence that retention
      of the attachment is an important factor for a patient's satisfaction. PURPOSE:
      This study describes retentive forces and wear of commercially available
      attachments of 4 implant systems (31, IMZ, Nobel Biocare, ITI Straumann) and 2
      magnets (Steco). METHODS: Forces while removing the keyway portion of an
      attachment in its path of insertion were measured with a platform load cell. A
      total of 15,000 removals were performed to simulate fatigue. RESULTS: Retentive
      forces ranged between 3 and 85 N. The fatigue test revealed an initial increase
      of forces with some attachments. After 15,000 cycles, most of the attachments
      showed little loss of retention compared with the initial retentive forces. It is
      suggested that conventional fatigue tests with application of axial loads do no
      simulate clinical fatigue adequately.

PMID- 9760366
TI  - Feedback control during mastication of solid food textures--a clinical
      experimental study.
AB  - STATEMENT OF PROBLEM: On the basis of animal experiments, it has been
      hypothesized that the dynamics of food reduction are controlled by peripheral
      receptors. Studies on this subject in human beings are rare. PURPOSE: This study
      investigated the influence of periodontal and joint proprioceptors on mastication
      in human beings. MATERIAL AND METHODS: Both jaw joints and the chewing-side teeth
      were consecutively anesthetized in a 6-person panel by chewing wine gum. The
      effects on the kinematics, chewing force, and electromyographic activity were
      measured. RESULTS: The results substantiate a positive feedback of periodontal
      receptors for chewing force control. A substantial influence of joint receptors
      on movement control could not be found. CONCLUSION: Despite the absence of
      proprioception in both jaw joints and the periodontal receptors in the chewing
      side, the characteristics of the measured kinematic and dynamic values remained
      essentially unchanged.

PMID- 9760368
TI  - Computer-assisted milling of dental restorations using a new CAD/CAM data
      acquisition system.
AB  - BACKGROUND: Recent technologic innovations have created possibilities for
      restorative dentistry, such as computer-aided design and computer-aided
      manufacturing (CAD/CAM). PURPOSE: This article presents a new CAD/CAM process
      that has been developed for the fabrication of dental restorations. METHODS: This
      process uses an improved imaging technique, successfully applied in other
      industries. Imaging is accomplished with 2-dimensional line grids projected onto
      an object, which allows for a mathematical reproduction of prepared and
      unprepared tooth surfaces, including those that are outside the direct line of
      light. The relative position of the sensor to the surface of the object is
      controlled automatically. CONCLUSIONS: This system, which is undergoing clinical
      testing, allows the generation of various types of highly accurate dental
      restorations (inlays, onlays, crown, and fixed partial dentures) from a number of
      different materials. Acquired digitized data points are directly translated from
      the sensor to the electronic controls of the milling machine to provide various
      manufacturing possibilities, including copy milling and accurate reproduction of
      occlusal tooth surfaces in various materials.

PMID- 9760367
TI  - Marginal fit and surface roughness of crowns made with an accelerated casting
      technique.
AB  - STATEMENT OF PROBLEM: Conventional investing and casting techniques following the
      manufactures' recommendations are time-consuming. Accelerated casting techniques
      have been reported, but their accuracy has not been adequately studied for
      complete crown castings. PURPOSE: This study evaluated the marginal fit and
      surface roughness of complete crowns made with a conventional and an accelerated
      casting technique. MATERIALS AND METHODS: Part I of the study determined the mean
      time interval required for each investment to reach its maximum exothermic
      setting reaction temperature. Part II determined the marginal discrepancy of
      standardized complete crowns cast in a high noble metal ceramic alloy, with the
      use of four phosphate-bonded investments. A conventional technique (as
      recommended by the manufacturer) was compared with an accelerated technique that
      used 13- to 17-minute bench set time (as determined in part 1 for each
      investment)_ and 15-minute wax elimination cycle in a 815 degrees C (1500 degrees
      F) preheated furnace. Part III evaluated the surface roughness of castings made
      with the same techniques as in part II. RESULTS: For the marginal discrepancy and
      surface roughness, crowns fabricated with the accelerated casting technique were
      not significantly (P > 0.05) different from those fabricated with the
      conventional technique. CONCLUSION: The accelerated casting technique described
      in this study could be a vital alternative to the time-consuming conventional
      techniques.

PMID- 9760369
TI  - Comparison of bond strengths of three denture base resins to treated nickel
      chromium-beryllium alloy.
AB  - PURPOSE: In-vitro bond strengths of 3 denture base resins (Trutone, Lucitone 199,
      and Triad) to a nickel-chromium-beryllium removable partial denture alloy
      (Ticonium) were tested with 3 surface pretreatments: sandblast, acid etch, and
      Rocatec (silica blasting), with or without primers (Dentsply, CR inlay cement,
      and Super Bond). MATERIAL AND METHODS: Lucitone 199 denture base resin bonded to
      the nonprimed sandblasted alloy specimen served as the control group. Alloy
      specimens were prepared, surface treated, and primed or not primed with primer.
      The treated specimens were then packed and processed with the denture base resin.
      Bonded specimens were stored in the distilled water at 37 degrees C for 24 hours,
      and then debonded in tension. The force at which the bond failed was noted, and
      bond strength was calculated in megapascals (MPa). Five replications for each
      condition (180 specimens total) were tested. RESULTS: Significant differences in
      bond strength were observed with primer, the most important factor, followed by
      pretreatment and denture base resin. Without primer for all 3 denture base
      resins, the Met-Etch and Rocatec treated group showed significantly higher bond
      strengths than the sandblasted groups. For Trutone denture base resin, nonprimed
      treated groups produced significantly higher bond strength than those for the
      other 2 denture base resin, nonprimed treated groups produced significantly
      higher bond strength than those for the other 2 denture base resins. The control
      group had zero bond strength. For Dentsply primer, the Rocatec treated group
      bonded to Lucitone 199 resin produced the highest bond strength value (14.8 +/-
      1.8 MPa). For CR inlay cement, the Met-Etch and Rocatec treated groups for
      Lucitone denture base resin demonstrated the highest bond strength (19.3 +/- 4.8
      MPa, and 19.3 +/- 1.8 MPa, respectively). For super Bond primer, the Met-Etch
      treated group for Trutone resin demonstrated the highest bond strength (19.8 +/-
      6.2 MPa). CONCLUSIONS: Without primer, the control had the lowest bond strength
      (0 MPa), and the Trutone groups showed the highest bond strength (11.7 +/- 4.1
      MPa). Met-Etch and Rocatec treated groups produced higher bond strengths than the
      sandblasted groups. The primed specimens demonstrated significantly higher bond
      strengths than nonprimed specimens, except for Trutone resin, for which primed
      specimens produced lower bond strengths than the nonprimed specimens.

PMID- 9760371
TI  - An esthetically attractive twin-flex clasp for removable partial dentures.
AB  - The cosmetic appearance of a removable partial denture is of great importance to
      both the patient and the dentist. Traditional facial clasp arms are usually
      unsightly. Other options are expensive and/or technically difficult, and may
      require time-consuming maintenance. Furthermore, when these clasps are broken,
      replacement of the entire removable partial denture may be required. This article
      describes a procedure for making a simple but effective twin-flex clasp. The
      clasp has excellent esthetics and can be readily adjusted or replaced.

PMID- 9760370
TI  - The effect of prosthodontic treatment on alveolar bone loss: a review of the
      literature.
AB  - STATEMENT OF PROBLEM: Complete, fixed partial, removable partial, and implant
      supported dentures have been used to comfortably and esthetically replace missing
      teeth. However, it is not certain what effect these prostheses have on the
      residual ridge. PURPOSE: This article compares various prosthetic treatments to
      restore completely and partially edentulous mouths for their ability to preserve
      residual alveolar bone. MATERIAL AND METHODS: A review of the literature was
      performed to discuss the effects of tooth replacement on residual alveolar bone.
      RESULTS: The literature seems to indicate that the presence of a dental
      prosthesis affects the size and form of the residual alveolar ridge and bone.
      CONCLUSION: An implant-supported fixed prosthesis to restore missing teeth in
      partially or completely edentulous jaws seems to be the best means of preserving
      residual alveolar bone.

PMID- 9760372
TI  - A new gingival retraction impression system for a one-stage root-form implant.
AB  - Displacement of soft tissue adjacent to an implant abutment is arduous.
      Currently, gingival retraction cord is used before making an impression for
      cement-retained implant restoration. This article presents a new impression
      system for a cementable abutment/implant. The advantages of a cement-retained
      implant crown are described. This system provides efficient and accurate
      impressions.

PMID- 9760373
TI  - The occlusal plane indicator: a new device for determining the inclination of the
      occlusal plane.
AB  - Accurate determination of the inclination of the occlusal plane is important in a
      number of situations, and includes confirming the correct development of the
      dentition in children, providing a basis for nonanatomic tooth design in the
      preparation of fixed prostheses, and assisting in decisions as to whether to
      perform intrusions or extrusions. This article describes a simple device for
      determination of the inclination of the occlusal plane.

PMID- 9760374
TI  - A new fully adjustable articulator system and procedure.
AB  - This article presents a simple and efficient articulator to help with the
      registration of maxillomandibular relationships, mounting casts, and subsequent
      perfection of the occlusal scheme for various types of prosthodontic
      restorations. The system (Individual Anatomo-Physiological system), which is
      composed of the articulator and recommended procedures, allows for registration
      of positions and trajectories of the mandible at the level of the patient's
      occlusal plane. It is used to accurately transfer the records to the articulator.
      A luminous signal shows the correct centric occlusal relationship and vertical
      dimension, in both clinical and laboratory procedures. Interocclusal records are
      used for semiadjustment of the articulator for provisional restorations and
      stereographic records are used for full adjustment of the articulator for
      definitive treatment.

PMID- 9760375
TI  - It's never too late to quit.

PMID- 9760376
TI  - Making sense of self-mutilation.

PMID- 9760378
TI  - Better medication compliance in teenagers with ADHD.

PMID- 9760377
TI  - Chronic headaches--more than just an aching head?

PMID- 9760379
TI  - Childhood trauma and adult illness.

PMID- 9760380
TI  - Updating what we know about depression in adolescents.
AB  - 1. Despite an 80% increase in prescriptions written for antidepressants for the
      treatment of pediatric depression, little empirical research has been done on the
      effects of antidepressant therapy on children and adolescents. 2. What little
      research has been done does not support the efficacy of antidepressants use in
      children. Moreover, some antidepressants may actually be harmful to pediatric
      populations. 3. Nurses have an obligation to keep abreast of the latest research
      findings in the literature because the knowledge base changes daily.

PMID- 9760381
TI  - The 5 R's of becoming a psychiatric nurse practitioner: rationale, readying,
      roles, rules, and reality.
AB  - 1. Psychiatric nurse practitioners (NPs) are advanced practice registered nurses
      who deliver primary mental health and psychiatric care to clients and families.
      2. Psychiatric NP curricula include advanced health assessment, pathology,
      pharmacology, NP role development, and psychiatric-mental health content, such as
      diagnosing and managing mental illnesses, providing therapies, and promoting
      mental health. 3. The degree of prescriptive autonomy of psychiatric NPs is
      determined by each state's Nurse Practice Act.

PMID- 9760383
TI  - Expertise in caring: a source of power.
AB  - 1. Caring generates power in relationships with patients and helps them to
      evolve. 2. Caring is more than an emotional response. It is acting in ways that
      demonstrate that people, relationships, and issues are important. 3. Continuity
      of care providers across settings help yield positive outcomes for patients.

PMID- 9760382
TI  - College students' AIDS risk perception.
AB  - 1. Students in this study appraised their AIDS risk using their sexual and drug
      use behavior as criteria, which accurately reflects their knowledge of HIV
      transmission. 2. AIDS risk perceptions were not always congruent with the
      students' self-reported sexual and drug use behavior. Some students reporting
      high-risk behavior perceived their AIDS risk as "nil" or "small." 3. Perceived
      riskiness of behavior increased as distance from the students increased. The
      students viewed their friends' AIDS risk as moderately greater than their own
      risk and their peers' risk even greater.

PMID- 9760384
TI  - Listening to the voice hearers.

PMID- 9760385
TI  - Audacious goals for health and biomedical informatics in the new millennium.
AB  - The 1998 Scientific Symposium of the American College of Medical Informatics
      (ACMI) was devoted to developing visions for the future of health care and
      biomedicine and a strategic agenda for health and biomedical informatics in
      support of those visions. This symposium focus was prompted by the many major
      changes currently underway in health care delivery, education, and research, as
      well as in our health and biomedical enterprises, and by the constantly
      increasing role of information technology in both shaping and enabling these
      changes. The three audacious goals developed for 2008 are a virtual health care
      databank, a national health care knowledge base, and a personal clinical health
      record.

PMID- 9760386
TI  - Then and now and when.
AB  - Since the 1970s, it has been clear that the health community needs to develop a
      health care system that matches a person's needs with the expertise and
      technology to address those needs. The logical solution is a multi-tiered system.
      In such a system, physicians would provide second- and third-tier services and
      other health professionals would provide first- and second-tier services. Medical
      informatics should take on the challenge of supporting the decision to triage
      patients from one tier of service to another. Triage decisions are different from
      other decisions in health sciences because they take place early in the life of a
      problem, when little information is available, and can be made safely if adjusted
      to tolerate erring on the side of referral.

PMID- 9760387
TI  - Directions for clinical research and genomic research into the next decade:
      implications for informatics.
AB  - Medical informatics is defined largely by its host disciplines in clinical and
      biological medicine, and to project the agenda for informatics into the next
      decade, the health community must envision the broad context of biomedical
      research. This paper is a sketch of this vision, taking into account pressures
      from changes in the U.S. health care system, the need for more objective
      information on which to base health care decisions, and the accelerating progress
      and clinical impact of genomics research. The lessons of modern genomics research
      demonstrate the power of computing and communication tools to facilitate rapid
      progress through the adoption of open community standards for information
      exchange and collaboration. While aspects of this vision are speculative, it
      seems clear that the core agenda for informatics must be the development of
      interoperating systems that can facilitate the secure gathering, interchange, and
      analysis of high-quality information and can gain leverage from worldwide
      collaboration in advancing and applying new medical knowledge.

PMID- 9760389
TI  - (Bio) medical informatics in the next decade.
AB  - Even though medical informatics is most often viewed from the perspective of its
      host disciplines in clinical and biologic medicine, it has an identity and agenda
      of its own. This paper is an attempt to promote discussion about the long-term
      role and agenda for medical informatics as a discipline into the next decade. The
      discussion has two main lines of argument, one about the "engineering" goals of
      informatics and the other about the "basic research" goals. These are, of course,
      influenced by ongoing of developments in computing, communications, and software
      infrastructures, but informatics is now mature enough that many of its goals
      transcend these changes.

PMID- 9760388
TI  - The networked health enterprise: a vision for 2008.
AB  - Informatics and information technology hold the promise of a consumer-centered
      health enterprise--one that provides quality care at a cost society is willing to
      pay; one where need-based, adaptive, competency-based learning results in cost
      effectiveness of health education; one where team-based health and learning on
      demand, coupled with monitoring of process outcomes and network access to
      expertise, guarantee quality. The barriers to this promise are the professional
      guilds, the cross-subsidies that support the health enterprise of 1998, and the
      lack of respect for privacy. Collectively, the informatics community needs to
      develop a compelling vision that will galvanize the health community to action.
      If the health community does not step up to this challenge, consumers will take
      advantage of disintermediation. Empowered by the network, they will go outside
      the system into hands that meet their needs.

PMID- 9760390
TI  - Representing thoughts, words, and things in the UMLS.
AB  - The authors describe a framework, based on the Ogden-Richards semiotic triangle,
      for understanding the relationship between the Unified Medical Language System
      (UMLS) and the source terminologies from which the UMLS derives its content. They
      pay particular attention to UMLS's Concept Unique Identifier (CUI) and the sense
      of "meaning" it represents as contrasted with the sense of "meaning" represented
      by the source terminologies. The CUI takes on emergent meaning through linkage to
      terms in different terminology systems. In some cases, a CUI's emergent meaning
      can differ significantly from the original sources' intended meanings of terms
      linked by that CUI. Identification of these different senses of meaning within
      the UMLS is consistent with historical themes of semantic interpretation of
      language. Examination of the UMLS within such a historical framework makes it
      possible to better understand the strengths and limitations of the UMLS approach
      for integrating disparate terminologic systems and to provide a model, or
      theoretic foundation, for evaluating the UMLS as a Possible World--that is, as a
      mathematical formalism that represents propositions about some perspective or
      interpretation of the physical world.

PMID- 9760391
TI  - A case study of the evolving software architecture for the FDA generic drug
      application process.
AB  - This primary goal of this project was to develop a software architecture to
      support the Food and Drug Administration (FDA) generic drug application process
      by making it more efficient and effective. The secondary goal was to produce a
      scalable, modular, and flexible architecture that could be generalized to other
      contexts in interorganizational health care communications. The system described
      here shows improvements over the old system for the generic drug application
      process for most of the defined design objectives. The modular, flexible design
      that produced this new system offers lessons for the general design of
      distributed health care information systems and points the way to robust
      application frameworks that will allow practical development and maintenance of a
      distributed infrastructure.

PMID- 9760392
TI  - Arizona Telemedicine Program: implementing a statewide health care network.
AB  - The Arizona Telemedicine Program was established in July 1996 by the Arizona
      state legislature. The organizational center for the program is the Arizona
      Health Sciences Center in Tucson. Key goals for the program include increased
      access to specialty services for rural, underserved populations; development of
      cost-effective telemedicine services; and expansion of opportunities for
      education of health professionals in rural areas. The program provides several
      levels of services based on both store-and-forward and real-time interactive
      applications. The telecommunication infrastructures is provided by two methods:
      The first is a private asynchronous transfer mode network established and
      operated by program personnel. The second is dial-up access via the public
      switched telephone network. After an extensive period of organization and vendor
      evaluations, most of the private network was implemented between June and
      December 1997. This paper describes experiences establishing the asynchronous
      transfer mode network.

PMID- 9760393
TI  - The structure of medical informatics journal literature.
AB  - OBJECTIVE: Medical informatics is an emergent interdisciplinary field described
      as drawing upon and contributing to both the health sciences and information
      sciences. The authors elucidate the disciplinary nature and internal structure of
      the field. DESIGN: To better understand the field's disciplinary nature, the
      authors examine the intercitation relationships of its journal literature. To
      determine its internal structure, they examined its journal cocitation patterns.
      MEASUREMENTS: The authors used data from the Science Citation Index (SCI) and
      Social Science Citation Index (SSCI) to perform intercitation studies among
      productive journal titles, and software routines from SPSS to perform
      multivariate data analyses on cocitation data for proposed core journals.
      RESULTS: Intercitation network analysis suggests that a core literature exists,
      one mark of a separate discipline. Multivariate analyses of cocitation data
      suggest that major focus areas within the field include biomedical engineering,
      biomedical computing, decision support, and education. The interpretable
      dimensions of multidimensional scaling maps differed for the SCI and SSCI data
      sets. Strong links to information science literature were not found. CONCLUSION:
      The authors saw indications of a core literature and of several major research
      fronts. The field appears to be viewed differently by authors writing in journals
      indexed by SCI from those writing in journals indexed by SSCI, with more emphasis
      placed on computers and engineering versus decision making by the former and more
      emphasis on theory versus application (clinical practice) by the latter.

PMID- 9760395
TI  - Recovery of Sarcocystis oocysts from a free-ranging wild dog (Lycaon pictus)

PMID- 9760396
TI  - Elbow dysplasia in the dog: pathophysiology, diagnosis and control.
AB  - Elbow dysplasia is a non-specific term denoting abnormal development of the
      elbow. Elbow dysplasia encompasses the clinical and radiographic manifestation of
      ununited anconeal process, fragmented medical coronoid process, osteochondritis
      dissecans, erosive cartilage lesions and elbow incongruity. The net result is
      elbow arthrosis, which may be clinically inapparent or result in marked lameness.
      These conditions may be diagnosed by means of routine or special radiographic
      views and other imaging modalities, or the precise cause of the arthrosis or
      lameness may remain undetermined. Breeds most commonly affected are the
      rottweiler, Bernese mountain dog, Labrador and golden retriever and the German
      shepherd dog. Certain breeds are more susceptible to a particular form of elbow
      dysplasia and more than 1 component may occur simultaneously. The various
      conditions are thought to result from osteochondrosis of the articular or physeal
      cartilage that results in disparate growth of the radius and ulna. Heritability
      has been proven for this polygenic condition and screening programmes to select
      suitable breeding stock have been initiated in several countries and have
      decreased the incidence of elbow dysplasia.

PMID- 9760394
TI  - Representing clinical guidelines in GLIF: individual and collaborative expertise.
AB  - OBJECTIVE: An evaluation of the cognitive processes used in the translation of a
      clinical guideline from text into an encoded form so that it can be shared among
      medical institutions. DESIGN: A comparative study at three sites regarding the
      generation of individual and collaborative representations of a guideline for the
      management of encephalopathy using the GuideLine Interchange Format (GLIF)
      developed by members of the InterMed Collaboratory. MEASUREMENTS: Using theories
      and methods of cognitive science, the study involves a detailed analysis of the
      cognitive processes used in generating representations in GLIF. The resulting
      process-outcome measures are used to compare subjects with various types of
      computer science or clinical expertise and from different institutions. RESULTS:
      Consistent with prior studies of text comprehension and expertise, the
      variability in strategies was found to be dependent on the degree of prior
      experience and knowledge of the domain. Differing both in content and structure,
      the representations developed by physicians were found to have additional
      information and organization not explicitly stated in the guidelines, reflecting
      the physicians' understanding of the underlying pathophysiology. The computer
      scientists developed more literal representations of the guidelines; addition
      were mostly limited to specifications mandated by the logic of GLIF itself.
      Collaboration between physicians and computer scientists resulted in consistent
      representations that were more than the sum of the separate parts, in that both
      domain-specific knowledge of medicine and generic knowledge of guideline
      structure were seamlessly integrated. CONCLUSION: Because of the variable
      construction of guideline representations, understanding the processes and
      limitations involved in their generation is important in developing strategies to
      construct shared representations that are both accurate and efficient. The
      encoded guidelines developed by teams that include both clinicians and experts in
      computer-based representations are preferable to those developed by individuals
      of either type working alone.

PMID- 9760397
TI  - Lack of susceptibility of Ehrlichia canis to imidocarb dipropionate in vitro.
AB  - In vitro antimicrobial susceptibility testing was used to compare the efficacy of
      imidocarb dipropionate and doxycycline on the growth of Ehrlichia canis in DH82
      cell cultures. Over a 9-day period there were no significant differences (p <
      0.01) in the growth of E. canis in untreated control wells and those to which
      imidocarb dipropionate was added at 1.2, 2.4, 4.8 or 12 micrograms/ml for the 1st
      3 days. Average infection rates rose from 50 to 55% on day 0 to 100% on day 5 or
      6. Doxycycline at 1 microgram/ml had residual or rickettsiocidal activity against
      E. canis with the average percentages of DH82 cells infected declining from 51 to
      24% while the organism was exposed to the drug (3 days) and from 21 to 2% in the
      6 days following removal of the drug from the cell culture medium.

PMID- 9760398
TI  - Urinary excretion of diethylstilbestrol in the ostrich.
AB  - Stilboestrol tablets (20 x 1 mg) were given to 4 ostriches. Urine was collected
      over a period of 8 days and stored frozen at-20 degrees C pending analysis.
      Analyses were performed on a gas chromatograph-mass selective detector for the
      presence of parent compound and/or metabolites. Diethylstilbestrol and its
      metabolite, dienestrol, were detected in urine; dienestrol only for 1 day but
      diethylstilbestrol for 8 days after administration. Residue analysis for the use
      of diethylstilbestrol as growth promoter can be performed on the urine of
      ostriches by scanning for parent compound only since it can be detected longer
      than the metabolite.

PMID- 9760399
TI  - Prevalence of gastro-oesophageal ulcers in grower-finisher pigs in the northern
      province of South Africa.
AB  - Ulceration of the gastric pars oesophagea is a common problem in intensive pig
      production that is often detected at slaughter. A survey was carried out at the
      Pietersburg abattoir in the Northern Province during a 6-month period. In total,
      4320 pig stomachs were examined. Gastro-oesophageal ulcers were observed in 5.1%
      of the stomachs, gastric erosion in 15.2%, and hyperkeratosis in 18.9%. Time of
      slaughter was found to affect the prevalence of gastric lesions in the pig.

PMID- 9760400
TI  - An outbreak of urticarial form of swine erysipelas in a medium-scale piggery in
      Kiambu District, Kenya.
AB  - This report concerns an outbreak that occurred during July/August 1997. Ten pigs
      from a herd of 181 pigs in a medium-scale, semi-closed piggery in Kiambu
      District, Kenya, contracted the clinical disease. The main clinical findings in
      affected pigs included: fever (40.5-41.8 degrees C), prostration, inappetence,
      dog-sitting posture, abortion, erythema and raised, firm to the touch and easily
      palpated light pink to dark purple diamond-shaped to square/rectangular spots on
      the skin around the belly and the back. Based on the pathognomonic skin lesions,
      a clinical diagnosis of swine erysipelas was made. The diagnosis was confirmed by
      the isolation of Erysipelothrix rhusiopathiae organisms from the blood and skin
      biopsies taken from the affected pigs. Response to treatment with a combination
      of procaine penicillin and dihydrostreptomycin at the dosage rate of 20,000 IU/kg
      body weight (based on procaine penicillin) for 3 days was good and all the
      affected pigs recovered fully. The farm was placed under quarantine to prevent
      spread of the disease.

PMID- 9760401
TI  - The zoonotic importance of Mycobacterium tuberculosis: transmission from human to
      monkey.
AB  - A case of zoonotic Mycobacterium tuberculosis infection in a marmoset (Callithrix
      jacchus) is reported. Genomic typing of the relevant M. tuberculosis isolates
      strongly suggests that the marmoset, which was kept as companion animal, acquired
      the disease from an infected member in the household who had been treated for
      pulmonary tuberculosis 8 years prior to this case.

PMID- 9760402
TI  - Healthy animals: safe products: a healthier community.

PMID- 9760403
TI  - [Toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino]
      benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (1). Single-dose intravenous
      toxicity studies in rats and dogs].
AB  - Single-dose toxicity studies of sodium N-[2-[4-(2,2-dimethylpropionyloxy)
      phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel
      neutrophil elastase inhibitor, were conducted in Sprague-Dawley (SD) rats and
      beagle dogs. The rats of both sexes were administered ONO-5046.Na intravenously
      at a single dose of 150, 300 or 450 mg/kg. The male dogs were also given ONO
      5046.Na at a single dose of 75 or 150 mg/kg. In the rat study, hypoactivity,
      bradypnea and paleness of limbs and pinna were observed at doses of 300 mg/kg and
      above. In particular, one of six female rats in the 450 mg/kg group showed clonic
      convulsion and died. In surviving animals, those signs disappeared within 3 hr
      after administration. No effect on body weight gain was seen in either group.
      Necropsy findings showed a slight foamy fluid in the bronchus, hemorrhage at the
      right knee joint muscle, tendon and lung in a dead animal. In the dog study, no
      effects on clinical signs, body weight, food consumption and blood biochemistry
      were seen in any animals of the 75 and 150 mg/kg groups. It is concluded that the
      approximate lethal doses are 450 mg/kg in rats and 150 mg/kg and above in dogs.

PMID- 9760405
TI  - [Toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino]
      benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (3). 4-week repeated dose
      intravenous toxicity study in dogs with 4-week recovery test].
AB  - 4-week repeated dose toxicity study with 4-week recovery test of sodium N-[2-[4
      (2, 2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate
      tetrahydrate (ONO-5046.Na), a novel neutrophil elastase inhibitor, was conducted
      in beagle dogs. The dogs of both sexes were administered ONO-5046.Na
      intravenously at a daily dose of 0 (vehicle control), 7.5, 15 or 30 mg/kg. In the
      15 mg/kg female group and the 30 mg/kg male and female groups, transient
      hypoactivity and ataxic gait were observed. It is considered that these symptoms
      were attributed to the pharmacological effect of ONO-5046.Na. Also, in the 30
      mg/kg male and female groups, erythrocyte, hematocrit and hemoglobin were
      decreased. In the 30 mg/kg male group, lung weight was increased. However,
      histopathological examination revealed there were no changes in any organs
      including the lungs. There were no treatment-related changes in body weights,
      food consumption, ophthalmology, occult blood in feces, urinalysis, blood
      chemistry, electrocardiography, blood pressure, temperature, pulse rate, hepatic
      and renal function or necropsy. These results indicate that the NOAEL of ONO
      5046.Na in dogs in 15 mg/kg/day for both sexes in this study.

PMID- 9760404
TI  - [Toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino]
      benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (2). 4-week repeated dose
      intravenous toxicity study in rats with 4-week recovery test].
AB  - A 4-week repeated dose toxicity study with 4-week recovery test of sodium N-[2-[4
      (2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate
      tetrahydrate (ONO-5046.Na), a novel neutrophil elastase inhibitor, was conducted
      in Sprague-Dawley (SD) rats. The rats of both sexes were administered ONO-5046.Na
      intravenously at a daily dose of 0 (vehicle control and saline control), 18.75,
      37.5, 75 or 150 mg/kg. ONO-5046.Na did not affect signs, body weight, food
      consumption, ophthalmology, urinalysis, hematology, blood chemistry, organ
      weights, necropsy or histopathology at any dose. These results indicate that the
      NOAEL of (ONO-5046.Na in rats is 150 mg/kg/day for both sexes in this study.

PMID- 9760406
TI  - [Toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino]
      benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (4). 6-month repeated dose
      intravenous toxicity study in rats with 1-month recovery test].
AB  - A 6-month repeated dose toxicity study with 1-month recovery test of sodium N-[2
      [4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate
      tetrahydrate (ONO-5046.Na), a novel neutrophil elastase inhibitor, was conducted
      in Sprague-Dawley (SD) rats. The rats of both sexes were administered ONO-5046.Na
      intravenously at a daily dose of 0 (vehicle control), 18.75, 37.5 or 75 mg/kg.
      ONO-5046.Na did not affect clinical signs, body weight, food consumption,
      opthalmology, urinalysis, hematology, blood chemistry, organ weight, necropsy or
      histopathology at any dose. These results indicate that the NOAEL of ONO-5046.Na
      in rats is 75 mg/kg/day for both sexes in this study.

PMID- 9760408
TI  - [Reproductive and developmental toxicity study of sodium N-[2-[4-(2,2
      dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate
      (ONO-5046.Na (1). Fertility study in rats].
AB  - Fertility study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino]
      benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel neutrophil elastase
      inhibitor, was conducted in Sprague-Dawley (SD) rats. ONO-5046.Na was
      administered intravenously at doses of 18.75, 37.5 and 75 mg/kg/day to male rats
      from 64 prior to mating, through the mating period and until necropsy, and to
      female rats from 15 days prior to mating until Day 7 of gestation, in order to
      examine its effects on fertility and reproductive performance of males and
      females and the development of their fetuses. There were no changes attributable
      to ONO-5046.Na in general signs, body weight, food consumption or autopsy
      findings in males and females. No drug-related changes were observed in estrous
      cycles, copulation and fertility indices in males and females. Pituitary weight
      of dams was decreased in each of the ONO-5046.Na treated groups, but no
      histopathological changes were observed in the pituitary. In the cesarean section
      findings in dams, ONO-5046.Na had no effects on the number of corpola lutea, the
      number of live fetuses, the implantation ratio, the resorbed and dead fetus
      ratio, fetal or placental weight, or the incidences of external, skeletal or
      visceral anomalies of the fetuses. From these results, it is considered that the
      NOAEL of ONO-5046.Na is 75 mg/kg/day for general and reproductive toxicity in
      males and females and for developmental toxicity in their fetuses.

PMID- 9760407
TI  - [Toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino]
      benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (5). 6-month repeated dose
      intravenous toxicity study in dogs with 1-month recovery test].
AB  - A 6-month repeated dose toxicity study with 1-month recovery test of sodium N-[2
      [4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate
      tetrahydrate (ONO-5046.Na), a novel neutrophil elastase inhibitor, was conducted
      in beagle dogs. The dogs of both sexes were administered ONO-5046.Na
      intravenously at a daily dose of 0 (vehicle control), 7.5, 15 or 30 mg/kg. In the
      15 mg/kg and above groups, transient ataxic gait was observed. It is considered
      that this symptom could be attributed to the pharmacological effect of ONO
      5046.Na. Macro- and microscopic hemorrhage at the injection site was observed in
      the ONO-5046.Na treated groups. However, it is considered that these findings
      could be attributed to the long-term repeated dosing procedure, and were not
      toxic changes. There were no treatment-related changes in body weight, food
      consumption, ophthalmology, urinalysis, hematology, blood chemistry,
      electrocardiography and organ weights. These results indicate that the NOAEL of
      ONO-5046.Na in dogs is 30 mg/kg/day for both sexes in this study.

PMID- 9760409
TI  - [Reproductive and developmental toxicity study of sodium N-[2-[4-(2,2
      dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate
      (ONO-5046.Na) (2). Study for effects on pre- and postnatal development in rats,
      including maternal function].
AB  - Prenatal and postnatal toxicity of sodium N-[2-[4-(2,2-dimethylpropionyloxy)
      phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel
      inhibitor of human neutrophil elastase, was studied in Sprague-Dawley (SD) rats.
      ONO-5046.Na was injected intravenously at doses of 0, 18.75, 37.5 and 75
      mg/kg/day to pregnant rats from day 7 of pregnancy to day 20 after delivery. All
      pregnant rats were allowed to deliver naturally for postnatal examination of
      their offspring. No adverse effects on dams were observed in clinical signs, body
      weight change, food consumption, pregnant, delivery or lactating performances.
      ONO-5046.Na did not affect the postnatal development of offspring, including
      birth index, survival index, physical and functional development, motor activity,
      emotionality, learning ability and reproductive performance. From these results,
      it is considered that the NOAEL of ONO-5046.Na is 75 mg/kg/day for dams and their
      offspring.

PMID- 9760410
TI  - [Reproductive and developmental toxicity study of sodium N-[2-[4-(2,2
      dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate
      (ONO-5046.Na) (3). Teratogenicity study in rabbits].
AB  - Teratogenicity of sodium N[2-[4-(2,2-dimethylpropionyloxy)
      phenylsulfonylamino]benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel
      inhibitor of human neutrophil elastase, was studied. ONO-5046.Na was injected
      intravenously at doses of 0, 7.5, 15 and 30 mg/kg/day to pregnant Kbl: NZW
      rabbits from day 6 to day 18 of pregnancy. All female rabbits were sacrificed on
      day 29 of pregnancy and their fetuses were examined. There were no clinical signs
      or death attributable to ONO-5046.Na. One dam in the control group and 3 dams in
      the 30 mg/kg/day group aborted. Body weight gain in the 15 and 20 mg/kg/day
      groups and food intake in the 30 mg/kg/day group were decreased during the
      administration period. These changes had recovered by the end of the study.
      Kidney weight was increased in the 30 mg/kg/day group. There were no effects of
      ONO-5046.Na in necropsy findings at cesarean section in dams at any dose levels.
      Developmental toxicity of ONO-5046.Na was not found at any dose levels. From
      these results, it is considered that the NOAEL of ONO-5046.Na is 7.5 mg/kg/day
      for pregnant animals and 30 mg/kg/day for fetuses.

PMID- 9760411
TI  - [Effects of mesalazine on liver carcinogenesis in medium-term bioassay using
      rats].
AB  - A two stage carcinogenesis promotion test using phenobarbital (PB) as a positive
      control was performed on mesalazine in rats (F344,male). Pathological and
      immunohistological examinations were performed to examine the cell damage and
      proliferation in the liver and kidneys. As the initiation treatment, groups 1,2,3
      and 5 were administered 300 mg/kg diethylnitrosamine (DEN)dissolved in 0.9%
      physiological saline, and group 4 was administered 5 ml/kg 0.9% physiological
      saline once intraperitoneally. Then group 1 was orally administered a water
      solution (5 ml/kg) containing 0.5% CMC-Na, and groups 2,3 and 4 similar water
      solution but containing 150, 300 and 300 mg/kg mesalazine, respectively. Group 5
      was administered 0.05% PB mixed in feed from weeks 2 to 8. Partial (2/3)
      hepatectomy was performed in all 5 groups at week 3 after DEN administration. NO
      clear differences between the groups were observed in general conditions, body
      weight or amount of food consumption. The number or area-size of hepatic GST-P
      positive altered cell foci revealed no significant differences between groups 1,2
      and 3, but a significant increase in number and area-size was observed in group
      5. No GST-P positive cell foci were detected in group 4. The number of altered
      cell foci (H.E. staining) in the DENgroups administered mesalazine was the same
      as that in group 1. Thus, mesalazine did not promote hepatocarcinogenesis in the
      present experimental system. Statistically insignificant appearances of
      basophilic and acidophilic changes were observed in the renal tubular epithelium
      and mineral deposits in the renal papillary region and cortical margin region.
      The PCNA labeling rate was significantly lower in group 4, corresponding with the
      histological finding showing no proliferation of the renal tubular epithelium.
      Judging from the above test results, mesalazine was likely to show neither a
      promotion effect on the initiation induced by DEN nor cell proliferative activity
      on the kidneys by administration for this experimental period.

PMID- 9760412
TI  - Skin sensitization and photosensitization studies of hydrophobically modified
      hydroxypropyl methylcellulose in guinea pigs.
AB  - Skin sensitization and photosensitization tests of hydrophobically modified
      hydroxypropyl methylcellulose (HM-HPMC), a new cellulose derivative used as a
      thickener for topical pharmaceuticals, were conducted using guinea pigs. An
      aqueous dispersion of HM-HPMC (3 w/v %) was applied in the tests. Skin reaction
      was not observed in any animal in the HM-HPMC-treated group or control group. In
      the photosensitization test, no skin reaction was found in any animal in the test
      preparation group or the control group. It was concluded that HM-HPMC dispersion
      does not exhibit skin sensitizing or photosensitizing activity under the
      condition of this test.

PMID- 9760414
TI  - Trace elements and apoptosis.
AB  - It is known that apoptosis is considered to be responsible for selective deletion
      of cells during embryogenesis, the homeostasis of cell populations in
      continuously renewing tissues (i.e., serving as a counterbalance to mitosis), and
      tissue involution in response to chemical or physical stimuli. There are many
      publications on these questions. On the other hand, the intracellular processes
      that contribute to apoptosis are incompletely understood. Therefore, the role of
      apoptosis in the intracellular accumulation and outflow of minerals is of
      considerable importance in light of both their essential functions and toxic
      effects.

PMID- 9760413
TI  - Thirteen-week repeated oral dose toxicity study of ecabapide, a gastroprokinetic
      drug, in dogs and rats.
AB  - Thirteen-week oral repeated dose toxicity of ecabapide, a gastroprokinetic drug,
      was investigated in dogs at dosage levels of 50, 175 or 600 mg/kg, and in rats at
      dosage levels of 25, 100, 400 or 1600 mg/kg. In dogs, vomiting, aqueous
      salivation, body weight gain inhibition, and hemolytic anemia, together with an
      increase in Heinz body formation, were observed at 175 and/or 600 mg/kg.
      Histological examination revealed enhanced hemosiderin deposition in the liver
      and spleen, retention of erythrocytes in the splenic sinus and enhanced
      erythropoiesis in bone marrow at 175 and/or 600 mg/kg. In the rat study, although
      increases in serum total protein, albumin and calcium, as well as increased liver
      and kidney weights, were observed at 400 and/or 1600 mg/kg, no obvious
      morphological changes were seen. The hemolytic anemia and an increased Heinz body
      formation were not observed in rats, indicating a species difference. On the
      basis of these results, the non-toxic dose of ecabapide was considered to be 50
      mg/kg in dogs and 100 mg/kg in rats.

PMID- 9760415
TI  - Organic and inorganic selenium supplementation to lactating mothers increase the
      blood and milk Se concentrations and Se intake by breast-fed infants.
AB  - The aim of this study was to determine the effect of selenium (Se)
      supplementation to lactating women on Se concentrations and glutathione
      peroxidase (GSH-Px) activities in blood components of mothers and breast-fed
      infants and on milk Se levels and Se intake by breast-fed infants. Lactating
      mothers were supplied for 3 months with 200 micrograms Se/day in the form of
      yeast-Se (Y-Se) and sodium selenite. Initial blood and plasma Se levels of all
      women (n = 67) were 76.6 and 53.2 micrograms/L, respectively. After 3 months Se
      concentrations both in whole blood and in plasma from mothers and infants were
      significantly higher than the initial values. Y-Se exerts a stronger effects than
      selenite on blood and plasma Se levels. Initial milk Se concentration was 8.9
      micrograms/L and after 1 month in both groups in reached a plateau at 14-16
      micrograms/L. This resulted in an increase of Se intake in breast-fed infants
      from 6.1 to a plateau of 11-13 micrograms Se/day. GSH-Px activities in plasma and
      red cells of Y-Se group increased significantly and reached a plateau after 1 and
      2 months, respectively, while in the selenite group the enzyme activities
      increased steadily throughout the entire period of the study. Selenite exerts a
      stronger effect on GSH-Px both in maternal and in infant blood components as
      compared with Y-Se. In milk the GSH-Px activity in the Y-Se group did not change
      during the study, while in the selenite group after 3 months it increased almost
      2-fold compared to the initial value. In conclusion, this study shows that
      organic Se causes higher Se deposition than did the inorganic form.

PMID- 9760416
TI  - Effects of thiamin and methionine administration in preventing cadmium-induced
      biochemical alterations and metal concentration in male rats.
AB  - Thiamin or methionine supplementation was equally and moderately effective in
      preventing the accumulation of cadmium in soft organs and alterations in a few
      selected biochemical indices during concomitant administration. Adequate intake
      of sulfur amino acid following methionine supplementation might increase the
      bioavailability of glutathione, facilitating the prevention of the binding of
      cadmium to different compartments and consequently reversing cadmium-induced
      biochemical disorders. In the case of thiamine the possibility of formation of a
      readily excretable complex between cadmium and thiamine or an increase in the
      body's resistance to cadmium might be the beneficial factor.

PMID- 9760417
TI  - Selenium, zinc and copper in plasma of patients with type 1 diabetes mellitus in
      different metabolic control states.
AB  - The Studies of selenium (Se), zinc (Zn) and copper (Cu) levels in diabetic
      patients have led to contradictory findings as the possible relationship between
      the degree of diabetic control and the changes in mineral contents. In the
      present study the plasma Cu, Se, and Zn contents of diabetic patients and healthy
      people were measured and the relationship between these contents and diabetic
      metabolic control, as determined by glycosylated hemoglobin (HbA1c), was studied.
      The mean plasma Se content in diabetic patients was significantly lower than in
      controls (p < 0.01) and a negative correlation between the plasma contents of Se
      and HbA1c was found. No statistically significant differences in plasma Zn
      contents, either between patients with type 1 diabetes mellitus and control, were
      found. A statistically significant sex difference in plasma Cu contents was
      observed in the control population. In females, statistically significant
      differences were found in plasma Cu contents between the control subjects and the
      diabetic patients with medium or poor metabolic control, as well as between
      diabetic patients with good and poor metabolic control. In males, the only
      statistically significant differences were between the control subjects and
      diabetic patients with poor metabolic control. The correlation between plasma
      contents of Cu and HbA1c is not significant.

PMID- 9760418
TI  - Study of the antioxidant effect of several selenium and sulphur compounds.
AB  - Four selenium derivatives (sodium selenate, sodium selenite, selenourea and
      selenomethionine) and the sulphur analogues (sodium sulfate, sodium sulfite,
      thiourea and methionine), together with urea, were examined by means of
      polarography to study their reactivity towards superoxide ion O2. In order that
      experimental results could be applied to physiological conditions and to control
      the electroreduction of oxygen, most reactions were carried out in model systems
      (in the presence and in the absence of triphenyl phosphine oxide and at
      increasing pH) which are briefly described and discussed. Sodium sulfite and
      thiourea react with molecular oxygen; selenourea originates an anodic wave,
      although under other pH conditions. Other compounds (selenate, selenite, seleno
      methionine and methionine) display an interesting antioxidant capacity because
      they catalyse the disproportion of the superoxide ion, as documented by the
      increase in the limiting current. Methionine appears to be particularly efficient
      in this respect, since it retains its catalytic ability in a poorly protic
      environment. Experimental results support the view that exogenous compounds,
      administered for particular purposes, can display unanticipated, and sometimes
      positive, side effects.

PMID- 9760420
TI  - Elements in autopsy liver tissue samples from Greenlandic Inuit and Danes. I.
      Sulphur, chlorine, potassium and bromine measured by X-ray fluorescence
      spectrometry.
AB  - The purpose of this study was to measure the content of the elements Sulphur (S),
      Chlorine (C1), Potassium (K) and Bromine (Br) in normal liver tissue samples from
      Greenlandic Inuit using X-ray fluorescence spectrometry, and compare the results
      with those obtained in normal liver tissue samples from Danes. Liver tissue
      sample were obtained at autopsy from 50 Greenlandic Inuit (27 men, 23 women) with
      a median age of 61 years (range 20-83) and from 74 Danes (44 men, 30 women) with
      a median age of 52 years (range 15-87). In Inuit, the content of elements given
      as median and (5-95 percentile) was: sulphur, 108.07 mmol/kg dry liver (86.78 -
      169.44); chlorine, 92.16 mmol/kg dry liver (45.39-128.42); potassium, 181.66
      mmol/kg dry liver (146.41-236.35); bromine, 0.0901 mmol/kg dry liver (0.0563
      0.1589). In Danes, the corresponding values were: sulphur, 147.58 mmol/kg dry
      liver (70.41-236.81); chlorine, 96.95 mmol/kg dry liver (54.01-162.52);
      potassium, 198.40 mmol/kg dry liver (150.68-256.37); bromine, 0.1101 mmol/kg dry
      liver (0.0701 - 0.4203). None of the elements displayed any significant gender
      difference, neither in Inuit nor in Danes. Inuit had a lower liver content of
      sulphur (p < 0.0001), potassium (p < 0.008) and bromine (p < 0.002) as compared
      with Danes.

PMID- 9760419
TI  - Chromium determination in osteoblast-like cell culture medium by catalytic
      cathodic stripping voltammetry with a mercury microelectrode.
AB  - A catalytic cathodic stripping voltammetric procedure for the determination of
      total chromium in osteoblast-like cell culture medium using a mercury film
      microelectrode (MFM) was optimised. The method is based on the pre-concentration
      of the Cr(III)-diethylenetriaminepentaacetic acid (DTPA) complex by adsorption at
      the potential of-1.00 V (vs. Ag/AgC1) in the presence of 10 x 10(-3) mol/L DTPA,
      0.70 mol/L sodium nitrate, 0.04 mol/L sodium acetate and 1.0 x 10(-3) mol/L
      potassium permanganate at pH 5.9-6.0. The limit of detection obtained for a 40 s
      collection time was 2.80 x 10(-10) mol/L of chromium. The results achieved by
      stripping voltammetry using the MFM were compared to those obtained by atomic
      absorption spectrometry (AAS) to ensure the reliability of the electrochemical
      method. This procedure proved to be an alternative to AAS and valuable in
      biocompatibility studies performed in vitro using osteoblast-like cells.

PMID- 9760421
TI  - Determination of nickel in saliva by electrothermal atomic absorption
      spectrometry using various chemical modifiers with Zeeman-effect background
      correction.
AB  - The profile of nickel signal using electrothermal atomic absorption spectrometry
      with deuterium and Zeeman-effect background correction is presented. The Zeeman
      effect system of background correction offered definitive advantages and
      therefore was used for the determination of nickel in saliva in the presence of
      various isomorphous metals. The highest nickel absorbance values corresponded at
      200, 300, 300, 300, 600, and 200 ng of Tb, Mg, Sm, Lu, Tm, and Pd, respectively.
      On the other hand, the addition of Eu, Er, and Ho decreased the nickel signal.
      The presence on each modifier alone does not eliminate the matrix interference.
      However, the use of 200 ng of Pd in conjuction with 300 ng of Lu has a higher
      sensitivity, offers an advantage against interference from the background of
      saliva matrix and produces good recoveries (98 to 102% from unspiked and spiked
      saliva samples). The limit of detection was 0.11 micrograms/L for a
      characteristic mass of 16.6 pg of nickel using Pd-Lu as modifier. The within
      batch precision varied between 0.8 and 1.5% relative standard deviations. The
      analysis of thirty samples of whole saliva gave an average of 0.81 +/- 0.30 of
      micrograms/L of Ni (range from 0.5 to 2.0 micrograms/L of Ni). The agreement
      between the observed and certified values obtained from a Seronorm Blood Serum
      Standard Reference Material was good.

PMID- 9760422
TI  - [Biology and growth velocity of tumors of the globus jugulotympanicum and glomus
      caroticum].
AB  - BACKGROUND: Paragangliomas (glomus tumors) of the head and neck are rare tumors,
      arising from the paragangliomatous tissue either of the carotid region or the
      jugular or the tympanic region. This study was conducted to investigate the
      possible differences in the tumor biology of these lesions depending on their
      site of origin. METHODS: Nineteen specimens (10 jugulotympanic and 9 carotid
      glomus tumors) were investigated by quantitative DNA measurements and
      immunohistochemical assessment of proliferation markers (PCNA, Ki67), oncogenes
      (p53, nm23), different cell surface antigenes (CD44 4/5 and 6, CD54, CD106), and
      bcl 2 as a marker for apoptosis. RESULTS: Depending on the location of the tumors
      these measurements revealed significant differences in tumor biology with higher
      proliferation scores and a higher number of aneuploid tumors in those of the
      carotid region, suggesting a more aggressive behavior compared to those of the
      jugulotympanic region. CONCLUSIONS: The results also indicate a difference
      between the two groups in the risk of developing metastases or recurrent disease.
      They generally help to enhance our understanding of the biology of paragangliomas
      of the head and neck.

PMID- 9760423
TI  - [Jugulotympanic paraganglioma: therapy concepts under development].
AB  - BACKGROUND: The operative treatment and radiation therapy of jugulotympanic
      paragangliomas (JTP) are still a matter of controversial discussion. In spite of
      various improvements during the last 50 years, selecting the appropriate
      treatment modality (surgery, radiation, or observation) is still a challenge.
      PATIENTS: During a 16-year period, 44 patients with 45 JTP (10 at level A/B and
      35 at level C/D according to Fisch) were seen at the ENT-department in Fulda.
      Forty-one cases were treated surgically. RESULTS: Complete resection was possible
      for level A/B in 100% of the patients (n = 10). Residual tumor was demonstrated
      for level C in 23% of the patients (5/22) and for level D in 40% (4/10) with a
      median follow-up time of 69 months. In two cases residual tumor was treated by
      radiation. Six patients with residual paraganglioma tissue were maintained under
      observation without any evidence of tumor progression (median follow-up time 39
      months). We report one death after the attempt to resect a large residual
      paraganglioma that had already caused brain stem compression. A sufficient
      duraplasty could not be achieved following radiation therapy. CONCLUSIONS:
      Complete tumor resection of jugulotympanic paragangliomas of levels A and B is
      often possible without injury to the cranial nerves. Extensive tumors present
      difficulties in complete tumor resection and increase the risk of cranial nerve
      injuries. Advanced paragangliomas therefore require an individualized therapeutic
      regime including surgery, radiation therapy, and observation of tumor growth.

PMID- 9760424
TI  - [Chronic mycoses of the paranasal sinuses--value of endonasal paranasal sinus
      surgery].
AB  - BACKGROUND: Many host factors even in immunocompetent patients may have an
      influence on development of a fungal diseases within the paranasal sinuses.
      Fungal sinusitis can occur in an acute form or more often to a chronic type of
      the disease. These mainly relatively asymptomatic chronic forms and further
      divided into a chronic noninvasive, chronic allergic, and chronic invasive
      disease. Endonasal microsurgery has significantly changed the management of
      chronic fungal sinusitis and allows adequate removal of pathologic tissue even in
      advanced situations. The aim of this study was to analyze the efficacy of
      endonasal surgery in chronic fungal sinusitis. MATERIAL AND METHODS: In a
      retrospective study we assessed a group of 40 patients who had endonasal surgery
      for chronic fungal sinusitis. Patient records, CT and MRI scans, microbiology and
      histology as well as the postoperative clinical follow-up including endoscopic
      photo documentation were evaluated over a period of 5 years. All patients
      underwent endonasal surgery using endoscopic techniques. The microscopic was of
      additional help in a few cases with extended disease and multiple dehiscences of
      the skull base. RESULTS: Twenty-four patients had a chronic noninvasive of fungal
      sinusitis and 16 patients had a chronic invasive form. All these patients
      underwent endonasal surgery without external incision. The fungal disease was
      erradicated in 39 cases, and revision surgery was required in only one case in
      which involvement of the contralateral side was not initially detected. in two
      cases scar tissue in the middle meatus was later excised but without evidence of
      residual fungal disease. Only in 6 cases was antifungal chemotherapy required,
      where the disease had spread into surrounding tissue or the patient had severe
      symptoms. CONCLUSIONS: Endonasal microsurgical techniques are today the
      appropriate approach for managing chronic fungal sinus disease even in severe
      cases with radiologic evidence of expansion or invasion of surrounding tissue.
      Additional antifungal chemotherapy is only rarely indicated, specifically when
      the fungal disease invades surrounding tissue.

PMID- 9760425
TI  - [Paranasal sinuses: only one of nature's games?].
AB  - BACKGROUND: Many theories exist concerning the function of paranasal sinuses, but
      it is rather difficult to definitively name the right one. Despite the fact that
      many of them have been proved to be wrong, they are still used. THEORIES: Galen
      postulated 2000 years ago that they were "porous bones", which helped with weight
      reduction. Like Galen's theory, most of the others have been refuted as well. A
      list of these refuted theories covers a range of postulated functions including a
      relative warming or moistening of the breath, protection against high pressure in
      the nasal region when sneezing, paranasal sinuses as a place of efficient mucus
      production, or an aid for smelling, similar to the ethmoidal cells of the
      porcupine. Others include an isolated function for protection against cold
      climates and an aid for formulating sound by acting as a resonance chambers.
      CONCLUSIONS: Two theories still remain. One says that the paranasal sinuses are
      only the result of the evolutionary processes that have taken place in the skull
      during human development. The other theory explain that the form of the paranasal
      sinuses exists through the influence of the forces created during the act of
      chewing. Small cavities appear as a result of the minimal energy created, and
      these cavities can be found in the form of paranasal sinuses.

PMID- 9760426
TI  - [Otogenic brain abscess].
AB  - BACKGROUND: Otogenic complications are rare but typical following acute or
      chronic ear infections like mastoiditis and cholesteatoma. A life-threatening
      sequela is the otogenic brain abscess located in the temporal lobe or cerebellum.
      PATIENTS: At the ENT Department of the Medical University of Hannover/Germany we
      treated 8 patients suffering from otogenic brain abscesses in the temporal lobe
      during the last three years. The average age of the 6 male and 2 female patients
      was 48 years. In 5 patients the abscess developed due to a cholesteatoma with
      superinfection. Three cases showed acute mastoiditis. All patients were operated
      using an otosurgical retroauricular approach, in five cases a classical radical
      mastoidectomy was performed. In two cases the abscess was reached via mastoidal
      approach and was subsequently drained. In two other cases the abscess was drained
      some days later by neurosurgical approach due to increased neurological symptoms.
      The other patients were treated with high-dosed antibiotics under regular
      clinical and radiological control. RESULTS: In 7 cases complete regression of the
      abscess was achieved. Five patients were discharged without further otological or
      central-nervous problems. One female patient developed severe meningitis with
      generalized thrombosis of the central blood sinus system and died in central
      circulatory failure. Two other patients developed a moderate psychopathologic
      syndrome and were admitted to rehabilitation institutions. CONCLUSIONS: The
      analysis of our patients shows that otogenic brain abscesses should be regarded
      especially as a severe complication of the untreated cholesteatoma. It is
      important to use modern imaging modalities like computer tomography or MRI for
      early detection of the intracerebral lesion and to perform an early otosurgical
      intervention. Under antibiotics and CT control, healing of this severe
      complication can be achieved in most cases. However, the danger of acute and
      chronic ear diseases has to be kept in mind in all medical disciplines.

PMID- 9760427
TI  - [Long-term outcome after reconstruction of the cranial base with ionomer cement].
AB  - BACKGROUND: Congenital, posttraumatic, inflammatory or tumours skull base lesions
      with CSF leakage require reconstruction to mechanically stabilize the CNS and to
      securely seal the CSF space. PATIENTS AND METHODS: Ionomeric cement was used from
      1988 until 1994 in 44 patients for skull base reconstruction at the Department of
      Otolaryngology-Head and Neck Surgery, University of Wurzburg. Thirty-five
      patients were reexamined. The longest follow-up time was 8 years. The program for
      the present follow-up study comprised a general ENT and neurological examination
      as well as CT scans of the skull base, MRI tomography of the CNS, and the
      determination of the aluminium plasma concentration. RESULTS: None of the
      patients reexamined presented with complaints. Neurological examinations and MRI
      tomography in all patients did not reveal any pathological finding related to
      ionomeric cement application. Aluminium plasma concentrations in patients who
      received ionomeric cement implantations were not significantly elevated when
      compared to controls. General ENT examinations and CT scans in thirty-two
      patients demonstrated regular postoperative findings. The cement at the anterior
      skull base was not covered completely by mucosa in three patients. In one these
      cases, CT scans revealed dislocation of the ionomeric cement so that revision
      surgery was performed for removal. None of the patients to date presented with a
      CSF leak. CONCLUSION: Long-term results of the present study show that ionomeric
      cement is a suitable material for closure of osseous skull base lesions to
      permanently seal the CSF space. These results, however, can only be obtained when
      handling and application of the material is adequate. Unfortunately, the
      production of ionomeric cement has been stopped since 1995 following four cases
      of aluminium encephalopathy reported in the literature.

PMID- 9760430
TI  - [Occupational medicine issues in Poland].

PMID- 9760428
TI  - [Reconstruction of the forehead region with tabula externa of the skull].
AB  - BACKGROUND: Calvarial bone graft is often used in reconstructive cranio-facial
      surgery. As most common three different forms can be distinguished: outer-table
      bone, full thickness grafts and composite flaps (bone with a periostal or
      muscular pedicle). PATIENT AND METHOD: An extensive fibrous dysplasia of the
      frontal region was removed in a 26 years old patient. Reconstruction was carried
      out with alloplastic material achieving a good esthetic result. Recurrent seroma
      and occurrence of a fistula demanded removal of the alloplastic material and en
      bloc reconstruction of the forehead region was accomplished with a parietal outer
      table graft. Within a follow-up time of one year a good esthetic and stable
      reconstruction has been achieved. CONCLUSION: Split-thickness calvarial bone is
      still a versatile graft in reconstruction of the forehead region. Although a low
      rate of side effects in harvesting calvarial bone grafts are in general expected,
      one has to be aware of dural lesions occuring in the donor site during
      craniotomy.

PMID- 9760429
TI  - [Interesting case no. 15. Double median neck cyst].

PMID- 9760431
TI  - [Occupational lead poisoning in Poland].
AB  - During the years 1970-1996, 8,414 cases (8,176 among men and 238 among women) of
      lead poisoning, recognised as occupational disease, were registered with the peak
      in 1972-1976 (500-800 cases per year). An in-depth analysis of 7,893 (men)
      reported in the period between 1970 and 1992 revealed that repeated poisonings in
      the same person were observed quite frequently. Among 4,556 men poisoned by lead
      during the period under study, in every third men the disease was diagnosed at
      least twice. Almost half of men with occupational lead poisoning received the
      occupational disease certification after the exposure lasting less than five
      years. The majority of persons poisoned by lead (64.3%) were employed in plants
      located in the Katowice voivodship. More than half of men with occupational lead
      poisoning (54.1%) was exposed to maximum concentrations of lead, exceeding MAC
      values by two hundred times. A diminishing number of occupational lead poisoning
      observed during the 1990s does not reflect a real-level of occupational exposure.
      The majority of cases reported apply to large plants or industrial complexes
      where the prevention of poisonings is rather well organised. But dispersed small
      production and service enterprises, where acute cases of poisoning may lead to
      irreversible organic changes create a great problem. One of the prerequisites for
      effective prevention of occupational lead poisoning is to identify and to make a
      complete inventory of workplaces where lead occurs, as well as to identify
      workposts hazardous to worker's health, and to monitor lead concentrations in the
      air.

PMID- 9760432
TI  - [Prevention of vibration syndrome in selected occupational groups in the
      metallurgy industry].
AB  - Medical examinations were carried out in a group of 297 men exposed to hand-arm
      vibration in the metallurgical industry. The group consisted of 93 rammers, 77
      grinders and 127 chippers. The level of vibration at workposts was also measured.
      The average occupational exposures exposed in years and total hours were as
      follows: in the group of rammers - 14.5 yrs and 19,954 h; grinders - 15.2 yrs and
      10,131 h; and chippers - 8.8 yrs and 5,444 h. The vibration-dose limit was
      exceeded by 5.0, 0.96 and 1.1 times, respectively. Raynaud's phenomenon was found
      significantly more frequent in chippers than in rammers or grinders. Medical
      examinations showed the highest health risk among chippers and the lowest among
      rammers. No correlation was found between intensity of mechanical vibration at
      the workplace and the biological response in groups examined. The results of the
      examinations provided evidence that different groups of workers require different
      preventive programmes.

PMID- 9760433
TI  - [Risk factors for premature birth. I. Analysis of selected factors in a group of
      non-working women].
AB  - Selected risk factors responsible for premature birth in a group of women non
      employed professionally were discussed. The analysis included demographic (age,
      education, marital status, maternal body weight, the number of previous
      pregnancies, as well as spontaneous and artificial abortions reported in
      interview), social (smoking, exposure to tobacco smoke, family economic status,
      standard of living conditions, and facilities used in running the household), and
      medical (maternal health status before and during pregnancy, and perinatal care)
      factors, as well as work load at home. The authors found low maternal body
      weight, genital bleeding during pregnancy and work overload at home to be the
      most significant risk factors.

PMID- 9760434
TI  - [Evaluation of binocular vision in persons employed at high work posts].
AB  - The study covered 250 workers, aged 20-63 years, employed at workposts over 3
      meters high. We analysed visual acuity, refraction, anterior segment, eye ground,
      visual field, colour vision and binocular vision. The study revealed that 20% of
      persons examined lack the stereoscopic vision ability. In conclusion it is
      suggested to use combined methods in order to evaluate binocular vision and
      certify ability to work at high workposts.

PMID- 9760435
TI  - [Detection of antibodies to Borrelia burgdorferi among forestry workers in North
      Eastern Poland].
AB  - The purpose of the study was to assess the incidence of Borrelia burgdorferi
      antibodies and clinical forms of Lyme borreliosis among forestry workers in north
      eastern Poland. The group studied consisted of 1,466 persons (297 women and 1,169
      men), aged 20-70 years. In 439 (23.81%) persons the presence of B. burgdorferi
      antibodies was detected in serum, in 271 (18.49%) persons active Lyme borreliosis
      was diagnosed and 78 (5.32%) persons were carriers of B. burgdorferi antibodies.
      Arthritis (43.84%) and neuroborreliosis (32.95%) were found to be the most common
      forms of borreliosis.

PMID- 9760436
TI  - [Exposure to electromagnetic fields with frequencies of 50 Hz and changes in the
      circulatory system in workers at electrical power stations].
AB  - Bearing in mind a great diffusion of electromagnetic fields (EMF) with power-line
      frequency (in Poland-50 Hz) both in the occupational and communal environments,
      it is not surprising that possible health effects related to this exposure evoke
      much interest. Electromagnetic fields may affect the circulatory and nervous
      systems because of theoretical probability that electric impulses, generated by
      external electric and magnetic fields, may disturb their functions. For this
      reason we have decided to evaluate the functioning of the circulatory system in
      persons occupationally exposed to power-line frequency electromagnetic fields by
      employing the most up-to-date methods facilitating the in-depth diagnosis of the
      circulatory system and neurovegetative mechanisms. The work presented focused on
      the evaluation of electrocardiographic changes. The study covered 63 workers of
      the transforming and distributing stations, aged 22-67 years (median 39 +/- 10),
      employed under exposure for 2-43 years (median 15 +/- 10). The control group
      consisted of 42 workers of radio link stations, aged 23-65 years (median 30 +/-
      14), employed in the similar system but not exposed to EMF, with employment
      duration of 1-42 years (median 13 +/- 4). All persons were subject to general
      medical examinations, resting ECG, and 24 h Holter monitoring. In addition, the
      level of exposure in individual workplaces was estimated following the
      measurements of the intensity of electric and magnetic fields. In workers of
      electromagnetic stations an increased risk for electrocardiographic disturbances
      was revealed. Under conditions of exposure to electric fields, observed in
      stations where workers were employed, the risk was increased by 10%.

PMID- 9760437
TI  - [Evaluation of exposure to halothane and ethyl alcohol among technicians
      responsible for maintenance of anesthesia equipment].
AB  - The authors discuss the measurements of exposure to halotane and ethyl alcohol
      among technicians responsible for maintenance of anaesthesiological instruments
      that occurs at various stages of maintenance work and in an operating room.

PMID- 9760438
TI  - [Absorption and dispersion of ultraviolet radiation in human skin].
AB  - The study was carried out in a group composed of 48 men. The linear coefficient
      and linear coefficient of dispersion of ultraviolet radiation (UVR) in the skin
      was measured for different wavelengths. The mean values were determined for four
      types of the skin in both ultraviolet A (UVA) and ultraviolet B (UVB) ranges from
      280 to 400 nm. The skin ability to absorb UVR decreases rapidly with decreasing
      wavelength. At wavelength of 280 nm, the coefficient of absorption changed within
      the range from 105 cm-1 (skin type II) to 160 cm-1 (skin type V), however, at
      wavelength of 400 nm it accounted only for 20 cm-1. A reciprocal relationship for
      scattering was found. The coefficient of dispersion changed within the range from
      3.5 cm-1 at wavelength of 280 nm to 12 cm-1 at wavelength of 400nm. The mechanism
      based on absorption predominated at a shorter wave range (UVB), while at a longer
      range (UVA) the scattering mechanism was more efficient.

PMID- 9760439
TI  - [Limitations in using international occupational disease statistics for
      comparative analysis].
AB  - The comparability of international statistical data on the incidence of
      occupational disease is discussed. The examples of some countries served to
      present the reasons why the relevant data available in publications cannot be
      often used as a frame of reference to comparative studies. The problem results
      mainly from different definitions of the term "occupational disease" as they
      frequently include in their context also these pathologies which are numbered
      among work-related diseases. In addition, the authors highlighted the steps
      undertaken by international organizations (World Health Organization,
      International Labour Organization, and European Union) to unify both the
      diagnostic procedures and the system of collecting and publishing of statistical
      data on occupational diseases.

PMID- 9760440
TI  - Progress in nephrotoxicology: from in vivo screening test to molecular
      mechanisms.

PMID- 9760441
TI  - Metallothionein transgenic and knock-out mouse models in the study of cadmium
      toxicity.
AB  - The role of MT in Cd toxicology has become clearer by the use of MT-I transgenic
      and MT-I and -II knock-out animals. We have shown that: (1) MT-transgenic and 
      null mice have altered tissue MT protein levels; (2) MT-transgenic and -null mice
      appear to be normal in other detoxifying systems examined, except for slight
      alterations in tissue Zn concentration; (3) MT does not appear to inhibit Cd
      absorption from the gastrointestinal tract, nor affect Cd tissue distribution;
      (4) MT reduces the elimination of Cd from liver; (5) MT protects against acute
      inorganic Cd-induced lethality and hepatotoxicity, and the mechanism of the
      protection appears to be due to its ability to sequester Cd in the cytosol, thus
      reducing the amount of Cd in critical organelles; (6) MT modulates Cd-induced
      expression of protooncogene(c-jin) and tumor suppress genes (p53) in mouse liver;
      (7) MT does not protect against CdMT-induced acute renal injury, and Zn-induced
      protection against CdMT-induced acute nephrotoxicity does not appear to be
      mediated through MT; (8) Chronic Cd administration produces renal injury inb MT
      null mice, indicating that Cd-induced nephrotoxicity is not necessarily mediated
      through the CdMT complex; (9) MT protects against chronic CdC12 nephropathy,
      suggesting that intracellular MT is an important adaptive mechanism decreasing
      CdC12 nephrotoxicity, and that a single injection of CdMT may not be a good model
      to study chronic Cd nephropathy; (10) genetic background of mouse strains, rather
      than constitutive MT levels, is a more important determinant for Cd-induced acute
      testicular injury. In addition to Cd detoxication, MT-transgenic and MT-null mice
      are also good models to determine other functions of MT. MT plays important roles
      in maintaining Zn homeostasis and protection against Zn toxicity. Knock-out of
      the MT gene also renders animals/cells more vulnerable to oxidative stress and
      DNA alkylating agent-induced toxicity. Therefore, the MT-transgenic and knock-out
      mouse models provide complementary approaches to those used previously, and have
      greatly increased our understanding of the role of MT in Cd toxicology, as well
      as other biological functions of MT.

PMID- 9760442
TI  - Medium-term bioassays as alternative carcinogenicity test.
AB  - A medium-term liver bioassay system for rapid detection of carcinogenic agents
      using male F344 rats has been developed, in order to bridge the gap between long
      term carcinogenicity tests and short-term screening assays. The system is
      fundamentally based on the two-stage hypothesis of carcinogenesis: initiation
      with diethylnitrosamine (200 mg/kg bw, i.p.) is followed by test chemical
      administration during the second, in combination with 2/3 partial hepatectomy. It
      requires only 8 weeks for animal experimental treatment and a further few weeks
      for quantitative analysis of immunohistochemically-demonstrated glutathione S
      transferase placental form positive hepatic foci. A total of 291
      chemicals/substances have already been analyzed in this laboratory and the
      efficacy of the system for hepatocarcinogens has thereby been well established.
      This bioassay is particularly useful for dose-response and chemical mixture
      studies, usually requiring large-scale experiments and also for evaluation of
      chemopreventive agents. Another bioassay, a medium-term multiorgan bioassay
      system, using 5 different chemical carcinogens, diethylnitrosamine (DEN), N
      methylnitrosourea (MNU), N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), 1,2
      dimethylhydrazine (DMH) and 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN), has
      also been established for rapid detection of not only hepatocarcinogens, but also
      other organ-target carcinogens. Rats were initially treated with a single i.p.
      administration of 100 mg/kg DEN, 4 i.p. administrations of 20 mg/kg MNU, 4 s.c.
      doses of 40 mg/kg DMH for 2 weeks and then 0.1% DHPN for 2 weeks. Test chemicals
      are administered after the carcinogens exposure. Animals were sacrificed at the
      end of week 36, and major organs were examined histologically. Carcinogenic
      activities of test chemicals were compared between the test chemical treated
      group and carcinogen exposures group (control group). It is increasingly becoming
      regarded that these bioassays are useful methods and are appropriate alternative
      tests systems for carcinogenicity risk assessment. Therefore, 'the International
      Conference on Harmonization (ICH) of Technical Requirements for the Registration
      of Pharmaceuticals for Human Use' has proposed that these two bioassays can be
      used as "additional tests for carcinogenic activity in vivo."

PMID- 9760443
TI  - The achievement and prospect of toxicology in China.

PMID- 9760444
TI  - Regulation of DNA damage inducible rhp51+ gene, a rec A homolog from
      Schizosaccharomyces pombe.

PMID- 9760445
TI  - Neuromuscular toxicity of anticholinesterase agents.

PMID- 9760446
TI  - Lead poisoning in waterfowl.

PMID- 9760447
TI  - Cycad poisoning in cattle in Japan--studies on spontaneous and experimental
      cases.

PMID- 9760448
TI  - Pharmacogenetics of CYP2C subfamily in a Japanese population.

PMID- 9760449
TI  - Aflatoxin B1 oxidation by human cytochrome P450s.

PMID- 9760450
TI  - UDPGT cDNA expression and UDPGT1 in human liver.
AB  - Following expression of UDPGTh1 and UDPGTh2 in Cos-1 cells, each isoform
      metabolized three types of dihydroxy- or trihydroxy-substituted ring structures,
      including the 3,4-catechol estrogen (4-hydroxyestrone), estriol and 17
      epiestriol, and hyodeoxycholic acid (HDCA), but the UDPGTh2 isozyme was 100-fold
      more efficient than UDPGTh1. UDPGTh1 and UDPGTh2 are 86% identical overall (76
      differences out of 528 amino acids), including 55 differences in the first 300
      amino acids of the amino terminus, a domain which confers isoform substrate
      specificity. The data indicate a high level of conservation in the amino terminus
      is not required for the preservation of substrate specificity. Analysis of
      glucuronidation activity encoded by UDPGTh1/UDPGTh2 chimeric cDNAs constructed at
      their common restriction sites, Sac I (codon 279), Nco I (codon 385), and Hha I
      (codon 469), showed that nine amino acids between residues 385 and 469 are
      important for catalytic efficiency, suggesting that this region represents a
      domain which is critical for catalysis but distinct from that responsible for
      aglycon selection. Screening of leukocyte DNA cosmid library with human UDPGT-Br1
      (1-470 bps) or UDPGT-Br2 (1-450 bps) resulted in three overlapping clones, which
      were isolated and mapped by endonucleases. Construction of subclones and DNA
      sequencing, Southern blot analysis revealed that a cluster of 4 exons (132, 88,
      220, 1032 bps in one clone) encodes the entire region of 3' identity shared
      between human UDPGT-phenol, human UDPGT-Br1 and human UDPGT-Br2. A similar
      strategy but using probes which correspond to the unique regions of human UDPGT
      Br1 and human UDPGT-Br2 showed that the exon 1 of UGT1A and UGT1D encodes the
      unique region of human UDPGT-Br1, and human UDPGT-Br2 and is located 5.6 and 49
      Kb, respectively, upstream of the 4 common exons.

PMID- 9760451
TI  - Genetic polymorphism of conjugating enzymes and cancer risk: GSTM1, GSTT1, NAT1
      and NAT2.

PMID- 9760452
TI  - Primary liver cancer: natural toxins and prevention in China.

PMID- 9760453
TI  - Fine structural changes and apoptotic cell death by T-2 mycotoxin.

PMID- 9760454
TI  - Monitoring of aflatoxin exposure by biomarkers.
AB  - Epidemiological studies have demonstrated a strong association between exposure
      to AFB1 and an increased incidence of human hepatocellular carcinoma (HCC). This
      association has led to a need for accurate techniques relating AF exposure to an
      individual's risk of developing disease. With the understanding of the
      progressive processes of carcinogenesis, opportunities for the identification of
      molecular biomarkers reflecting events from exposure through clinical disease are
      provided. However, the development of biomarker methods to monitor human exposure
      to AFs requires techniques which are sensitive, specific, and amenable to large
      numbers of samples. To better understand the role of AF exposure with respect to
      HCC incidence, immunoassays for the biological quantitation of free AFB1, its
      metabolites, and its adduct macromolecules have been developed. ELISA appears to
      offer a suitable method for use in epidemiological studies for monitoring short
      term exposure to AFs, as it has the appropriate sensitivity and specificity.
      However, the presence of substances that are presumably not AFs and which are
      inhibitory in the ELISA system has necessitated the development of purification
      techniques, usually based on adsorption onto Sep-Pak C18 cartridges and
      immunoaffinity chromatography. Many protocols have been developed for the assay
      of soluble AF metabolites in urine, milk and blood. However, these assays only
      indicate recent exposure, whereas the presence of albumin-AFB1 adducts in
      peripheral blood could present a useful material for assessing longer-term
      exposure. Among the various possible biomarkers of AF exposure, the measurements
      of AF-DNA and -protein adducts are of major interest because they are direct
      products of damage to a critical cellular macromolecular target. In Thailand, AF
      contamination of foods was reported to be high. More recent data using biomarkers
      as measures of AF exposure will be discussed. The data from epidemiological
      studies, AF exposure assessment using AF-albumin adduct and urinary AF level as
      exposure markers as well as the prevalence of p53 mutation at codon 249 are all
      suggestive of a limited importance of AF in the etiology of HCC in this country
      compared to other areas, including parts of Africa and China. These results also
      indicate that research on other potential hepatocarcinogens should not be
      neglected.

PMID- 9760455
TI  - Mycotoxins and health hazards: toxicological aspects and mechanism of action of
      fumonisins.

PMID- 9760456
TI  - How aspartame prevents the toxicity of ochratoxin A.
AB  - The ubiquitous mycotoxin ochratoxin A (OTA) is found as a frequent contaminant of
      a large variety of food and feed and beverage such as beer, coffee and win. It is
      produced as a secondary metabolite of moulds from Aspergillus and Penicillium
      genera. Ochratoxin A has been shown experimentally to inhibit protein synthesis
      by competition with phenylalanine its structural analogue and also to enhance
      oxygen reactive radicals production. The combination of these basic mechanisms
      with the unusual long plasma half-life time (35 days in non-human primates and in
      humans), the metabolisation of OTA into still active derivatives and glutathione
      conjugate both potentially reactive with cellular macromolecules including DNA
      could explain the multiple toxic effects, cytotoxicity, teratogenicity,
      genotoxicity, mutagenicity and carcinogenicity. A relation was first recognised
      between exposure to OTA in the Balkan geographical area and Balkan Endemic
      Nephropathy (BEN) with a high incidence (nearly 50 times higher than normal) of
      urinary tract tumours. Exposure rates of OTA are measurable in blood of humans
      and animals and are established in several countries including Scandinavia,
      Germany, France, Italy, Canada, Japan and Northern Africa mainly Tunisia and
      Egypt. The impact of OTA exposure in non- endemic areas in the world is not
      known, the rates of exposure being not correlated with the disease records,
      especially in developed countries, due to lake of well- designed epidemiological
      studies, genetic polymorphism and maybe to dietary contents of radical scavengers
      and antioxidants. However the incidence and mortality rates of renal cancer are
      increasing in European countries and Northern Africa which could be a global
      resultant of human exposure to natural compounds in food such as mycotoxins and
      especially ochratoxin A. In addition to special care to prevent the growth of
      moulds and detoxification measures there was a need for the prevention of the OTA
      induced toxic effects once the toxin is ingested. For this purpose several
      compound have been studied including some therapeutic agents such as piroxicam
      which cannot be proposed for a large scale use in humans for preventive purpose.
      Among other compounds, Aspartame, already used as sweetener has shown a real
      effectiveness in vivo confirmed largely in vitro. When rats exposed to OTA (289
      micrograms/kg) by oral route every two days are given 25 mg/kg similarly for
      several weeks, all the toxic effects including genotoxicity are very efficiently
      prevented as shown for example by the disappearance of DNA- adducts in tissues
      excised from treated animals. Aspartame is also effective in washing out the
      toxin when given afterwards to animals intoxicated by the same oTA doses for
      several weeks. In vitro, provided that it is added in cell culture medium before
      OTA it prevent significantly the inhibition of protein synthesis and lipid
      peroxidation induced by the toxin. Obviously the molecular mechanism mediating
      the preventive effect of Aspartame is the delivery of phenylalanine by cleavage
      of the peptide but also the direct effect of the peptide on the bending capacity
      and transport of the toxin in vivo and in vitro. As a matter of fact when
      Aspartame is given to animals or added in culture medium the amount of peptide
      found unchanged (10-15%) may account for a preventive effect as entire peptide.

PMID- 9760457
TI  - Current status of aflatoxin and its control in Thailand.

PMID- 9760458
TI  - Toxicity of beta-amyloid peptide.

PMID- 9760459
TI  - Excitatory amino acids and lead-induced neurotoxicity.
AB  - The NMDA receptor non-competitive antagonist, [3H]MK-801, was used as a ligand
      for an autoradiographic study to determine the effects of lead on NMDA receptor
      in rat brain. Adult male rats were given lead acetate, 100 mg/kg, or sodium
      acetate, 36 mg/kg (control), by i.p. for 7 days. Lead levels were detected in
      blood (41.1 micrograms/dl) and brain (16.7-29.4 micrograms/g). Concentrations of
      lead in various brain regions did not differ. [3H]MK-801 binding was
      heterogeneous throughout the brain with the following order of binding densities:
      hippocampal formation > cortex > caudate-putamen > thalamus > brainstem. Lead
      exposure caused a decrease in [3H]MK-801 binding to NMDA receptors in the
      hippocampal formation including CA2 stratum radiatum, CA3 stratum radiatum and
      presubiculum, and in the agranular insular, cingulate, entorhinal, orbital,
      parietal and perirhinal areas of cerebral cortex. In another experiment, female
      rats were exposed pre- and post-natally from the 4th +/- 1 post conception day
      with 1,000 ppm lead in their drinking water. This treatment continued after
      weaning. No effects of lead on [3H]MK-801 binding were found at postnatal day
      (PM) 28. However, lead caused a significant increase in [3H]MK-801 binding in the
      hippocampus including CA1 and CA2, and in the occipital and temporal cortical
      areas at PN 56 and at PN 112. Increases in [3H]MK-801 binding were also found in
      entorhinal cortex and dentate gyrus at PN 112. The hippocampal formation is a
      critical neural structure for learning and memory processes, whereas cortical and
      subcortical regions are involved in the modulation of complex behavioral
      processes. NMDA receptors have been shown to play a key role in synaptic
      plasticity underlying learning and memory. Therefore, lead-induced alterations of
      ligand binding to NMDA receptors in the hippocampal formation and cortical areas
      may play a role in lead-induced neurotoxicity.

PMID- 9760460
TI  - Mechanism of MPP(+)-induced cytotoxicity in human neuroblastoma SH-SY5Y.

PMID- 9760461
TI  - Territrem: neurotoxicity and biotransformation.

PMID- 9760462
TI  - Research on drug dependence and epidemiological investigation of drug abuse in
      China.

PMID- 9760463
TI  - Substance abuse in Taiwan and the role of clinical toxicology in its prevention
      and treatment.

PMID- 9760464
TI  - Drug abuse trends and epidemiological aspects of drug associated deaths in Korea.

PMID- 9760465
TI  - Drug abuse and toxicological scene in Japan.

PMID- 9760466
TI  - Toxicokinetic parameters in the management of poisoning: an example of
      podophyllotoxin intoxication.

PMID- 9760468
TI  - Toxicokinetics: concepts and applications.

PMID- 9760467
TI  - Toxicokinetics and safety factors in risk assessment.
AB  - For risk assessment of anticholinesterase pesticides, acetylcholinesterase
      inhibition is a sensitive, reversible indicator of exposure. However, use of
      smaller factors when data are available in human may not be justified in some
      specific cases. Direct action of anticholinesterase on receptor sites at various
      cell types in different target organs may yield to the more severe nature of
      toxicity. At the present time, uncertainties exist due to our limited capability
      to clarify many human diseases with complex etiology. The toxicokinetic models
      available may not accommodate some type of toxicants which their mode of action
      involve haemodynamic change or vascular cell injury. Anticholinesterase
      pesticides are still widely used in many asian countries to control a variety of
      pest species in agricultural practices. The physiology of the effects of these
      agents are complex and appropriate uncertainty or "safety factors" are needed to
      be acknowledged and taken into account from total exposure. Risk assessment of
      anticholinesterase agents is related to complex biological system and we will
      probably, never, at least in our lifetimes, know everything we would like to know
      to assess risk. We can only do our best with current information available.
      However, one should be extremely careful and holistic when applying these
      uncertainties in risk assessment of anticholine-esterase pesticides.

PMID- 9760469
TI  - Biochemical and pharmacological properties of thrombin-like protein from
      Agkistrodon caliginosus.

PMID- 9760470
TI  - Mutagenicity and antimutagenicity of flavonoids extracted from Millingtonia
      hortensis L.

PMID- 9760471
TI  - Pharmacology and toxicology of herbal medicine: subacute toxicity of commonly
      used Chinese drugs.

PMID- 9760472
TI  - Protective effect of a traditional medicine, shimotsu-to, on brain lesion in
      rats.

PMID- 9760473
TI  - Lead--the toxic metal to stay with human.
AB  - Lead has been known to be toxic to most living things at high dose. It is found
      naturally in earth and present in almost all parts of the environment, such as
      foods, air, water, dust, soil, paint, and tissues of living organisms including
      human. This metal is being used in various aspects including the manufacturing of
      storage batteries, production of chemicals, paints and gasoline additives. It is
      also used to make various metal products, e.g. sheet lead, solder, and pipes.
      Human exposure to lead is mainly from foods and other environments. However, it
      is expected that exposure to environmental lead is normally excessive and
      produces toxic effects. The well-known and excessive environmental exposures are
      air of industrial and heavy traffic areas. Use of leaded gasoline has caused the
      main lead pollution for years in almost every big city. Therefore, city
      inhabitants normally exposed to lead much more than those who live in the rural
      area. The most vulnerable groups at risk to lead exposure are fetuses and
      preschool age children. Young children in the 2-3 year-old age may be the most at
      risk for exposure to contaminated soil. Adults are affected when exposure is
      excessive in the working place and causing lead poisoning. Toxicities are mainly
      on heme biosynthesis, neurological effects including encepharopathy, peripheral
      neuropathy, and most importantly on I.Q. deficits. It also affects renal tissues
      to produce acute and chronic nephropathy and elevated blood pressure. There are
      studies of lead exposure of various means and the effects on human health, both
      in children and adults. Lead in environment and human exposure are expected to
      stay with us for long to come, due the still required lead use in many fields,
      particularly the use of lead in storage batteries and others. The magnitude of
      exposure will depend solely on the control of use by not allowing the
      contamination of lead in our environment to be excessive.

PMID- 9760474
TI  - Occupational and environmental lead poisoning: case study of a battery recycling
      smelter in Taiwan.
AB  - The rapid industrialization in Taiwan has caused both prosperity and
      environmental pollution. The purpose of this study is to demonstrate a case of
      both occupational and environmental lead poisoning. A patient of lead poisoning
      initiated a survey of the battery recycling factory, which revealed that 31 of 64
      workers suffered from lead poisoning. Children who attended a nearby kindergarten
      showed a significant increase of blood lead up to 15-25 micrograms/dl and a mild
      but significant decrease of IQ (intelligent quotient, by Binet-Simon scale) if
      compared with children of a nonexposed but socioeconomically comparable
      kindergarten. Outdoor workers of the nearby forging factory also showed a
      significant increase of blood lead if compared with indoor workers or workers of
      another nonexposed forging factory 20 Km away. Air sampling showed an average of
      more than 10 micrograms/m3 in the kindergarten. Soil sampling and analysis also
      revealed 400 folds increase of lead content, which decreased if the sample was
      taken deep down to 15-30 cm or 350 meters away from the battery recycling
      smelter. Moreover, after children were moved away from the pollution source,
      follow-up examination performed 2.5 years later showed a significant decrease of
      blood lead and partial recovery of IQ among them.

PMID- 9760475
TI  - Effects of Mg and K deficiency on male and female mice.

PMID- 9760476
TI  - Biological monitoring of metabolites of sarin and its by-products in human urine
      samples.
AB  - More than 20,000 passengers of Tokyo underground trains were intoxicated with
      warfare toxic chemicals. Most of the patients examined had marked miosis and
      decreased serum cholinesterase activity. Transient increase of serum CPK activity
      after 3 days of the exposure was the another sign. We intensively analyzed the
      metabolites in the urine of 4 patients. The following analytic results indicated
      the exposure to sarin as well as contaminated compounds such as diisopropyl
      methylphosphonate (DIMP), ethyl methylphosphonate fluoridate (EMPF, or
      ethylsarin), diethyl methylphosphonate (DEMP), and ethyl isopropyl
      methylphosphonate (EIMP). (1) Isopropanol (IPA) and ethanol (EtOH) were detected
      of large quantities in the urine samples, and were thought to be derived from
      sarin and the sarin counterpart, EMPF, DIMP, DEMP and EIMP. (2) Monoalkyl
      methylphosphonic acids (isopropyl methylphosphonic acid (IMPA) and ethyl
      methylphosphonic acid (EMPA) also were excreted in large amounts with taking the
      similar excretion pattern of IPA and EtOH. (3) The metabolite only derived from
      sarin and ethylsarin is F anions whose integral output in the urine was less than
      the equimolar level of the excreted (IMPA + EMPA + IPA + EtOH). (4) Other
      corroborative findings were low lethality: of more than 5,510 patients treated,
      11 were acutely dead. (5) Nine exposed males had higher sister chromatid exchange
      (SCE) rate (5.00 +/- 1.48/cell) than the control (3.81 +/- 0.697/cell), because
      dialkyl methylphosphonates seemed to have alkylating activity and producing DNA
      adducts. The SCE rate also increased after the in vitro exposure of lymphocytes
      to dialkyl methylphosphonates.

PMID- 9760477
TI  - Recent progress of the international harmonization of toxicological testing:
      impact and implementation of ICH guidelines. International Conference
      Harmonization.

PMID- 9760478
TI  - Testing human pharmaceuticals for carcinogenic potential: new approach in ICH
      process. International Conference Harmonization.

PMID- 9760479
TI  - Harmonization of genotoxicity testing requirements for pharmaceuticals.

PMID- 9760480
TI  - Recent progress of the international harmonization of toxicological testing:
      toxicokinetics.

PMID- 9760481
TI  - Registration of toxicologists in Europe.
AB  - Recently several European Toxicological Societies have established national
      toxicology registers. Such societies include the British, Dutch, Finnish, French,
      Hungarian, and Swiss societies of toxicology. The basis for registration in these
      societies is peer review evaluation of the applicants. A key-criterion for
      acceptance is theoretical training covering the main areas of toxicology.
      Furthermore, job experience is required. After reviewing the merits of the
      applicant, the register then accepts the applicant to the register usually for
      five years. As a consequence of this development, EUROTOX, European Societies of
      Toxicology, has established a European Register of Toxicologists which will be
      officially inaugurated during 1997. The register already contains more than two
      hundred British, Dutch, Finnish, and German toxicologists. The European Register
      of Toxicologists already has had an impact on the recognition of toxicology in
      Europe, and will strive to promote toxicology education and professional status
      in other parts of the world.

PMID- 9760483
TI  - The recent situation and future perspectives of the certification of
      toxicologists.

PMID- 9760482
TI  - Recent situation and future perspectives of the certification of toxicologists.

PMID- 9760484
TI  - Recent situation and future perspective of the certification of toxicologist in
      Japan.

PMID- 9760485
TI  - The present and future of poison control center in Taiwan.
AB  - The PCC-Taiwan was founded in July 1985 under the auspices of the Department of
      Health, Executive Yuan, and the Veterans General Hospital-Taipei, Republic of
      China. It has served a population of 21 million inhabitants on a 24-hours basis.
      It has also served as a referral center for treating poisoning cases nationwide,
      a training center for physicians and consultants, and a center for Analytical
      Toxicology. The average annual volume of telephone inquires to PCC is more than
      four thousand in recent few years and continue to increase annually. The present
      and future prospective of the PCC-Taiwan which have to be accomplished are: 1. to
      propagate public education of poisoning prevention and increase the utility of
      PCC before events of intoxication, 2. to establish, computerize and improve the
      database and network of domestic poisonous products or natural toxins, including
      herbs, 3. to establish an nationwide referral network for severely poisoned
      patients or cluster poisoning events, 4. to build up a global collaborative work
      with other poison centers.

PMID- 9760486
TI  - Recent situation of prevention, preparedness and response to chemical accidents
      in the Republic of Korea.

PMID- 9760487
TI  - Recent situation of the poison center in Thailand.

PMID- 9760488
TI  - Psychic dependent potential of dihydroetorphine.

PMID- 9760489
TI  - Introduction to plant virology.

PMID- 9760490
TI  - Introduction to classical crossprotection.

PMID- 9760491
TI  - History of coat protein-mediated protection.
AB  - A decade of research has proven that plants can be genetically engineered to
      resist virus infection through expression of viral CP genes, as well as other
      viral genes and sequences. Additional opportunities for development of resistant
      plants will require research focused on mechanisms of protection, improvements in
      expression vector design, and transformation of new crop species. As each of
      these technologies is utilized singly or in combination to generate resistant
      crop varieties, the full impact of such engineered resistance will be realized.

PMID- 9760492
TI  - Geminivirus isolation and DNA extraction.

PMID- 9760493
TI  - Caulimovirus isolation and DNA extraction.

PMID- 9760494
TI  - Reovirus isolation and RNA extraction.

PMID- 9760495
TI  - Procedures for plant rhabdovirus purification, polyribosome isolation, and
      replicase extraction.

PMID- 9760496
TI  - Hordeivirus isolation and RNA extraction.

PMID- 9760497
TI  - Furovirus isolation and RNA extraction.

PMID- 9760498
TI  - Tobravirus isolation and RNA extraction.

PMID- 9760499
TI  - Tobamovirus isolation and RNA extraction.

PMID- 9760500
TI  - Potexvirus isolation and RNA extraction.

PMID- 9760501
TI  - Carlavirus isolation and RNA extraction.

PMID- 9760502
TI  - Potyvirus isolation and RNA extraction.

PMID- 9760503
TI  - Trichovirus isolation and RNA extraction.

PMID- 9760504
TI  - Ilarvirus isolation and RNA extraction.

PMID- 9760505
TI  - Bromovirus isolation and RNA extraction.

PMID- 9760506
TI  - Cucumovirus isolation and RNA extraction.

PMID- 9760507
TI  - Nepovirus isolation and RNA extraction.

PMID- 9760508
TI  - Comovirus isolation and RNA extraction.

PMID- 9760509
TI  - Carmovirus isolation and RNA extraction.

PMID- 9760510
TI  - Tymovirus isolation and genomic RNA extraction.

PMID- 9760511
TI  - Tombusvirus isolation and RNA extraction.

PMID- 9760512
TI  - Luteovirus isolation and RNA extraction.

PMID- 9760513
TI  - RNA analysis. Size and 3' end group determination.

PMID- 9760514
TI  - RNA fractionation by density gradient centrifugation.

PMID- 9760515
TI  - cDNA library construction for the lambda ZAP-based vectors.

PMID- 9760516
TI  - PCR cloning of coat protein genes.

PMID- 9760517
TI  - Antibody production.

PMID- 9760518
TI  - Expression library screening.

PMID- 9760519
TI  - In vitro transcription and translation.

PMID- 9760520
TI  - Analysis of coat protein expression cassettes in protoplasts.

PMID- 9760521
TI  - DNA sequencing.

PMID- 9760522
TI  - Computer analysis of amino acid sequences. The case of plant virus capsid
      proteins.

PMID- 9760523
TI  - Preparation of coat protein-containing binary vectors for use in Agrobacterium
      mediated transformation.

PMID- 9760524
TI  - Potato transformation.

PMID- 9760525
TI  - Transformation of tomato.

PMID- 9760526
TI  - Tobacco transformation.

PMID- 9760527
TI  - Genetic transformation of wheat.

PMID- 9760528
TI  - Production of transgenic rice (Oryza sativa subspecies japonica cv. Taipei 309).

PMID- 9760529
TI  - Molecular analysis of transgenic rice.

PMID- 9760530
TI  - PCR analysis of transgenic tobacco plants.

PMID- 9760531
TI  - Southern analysis of transgenic tobacco plants.

PMID- 9760532
TI  - Detection and quantification of transcript RNA in transgenic plants using
      digoxigenin-labeled cDNA probes.

PMID- 9760533
TI  - Western analysis of transgenic plants.

PMID- 9760534
TI  - Assaying levels of plant virus by ELISA.

PMID- 9760535
TI  - Detection of plant RNA viruses by nonisotopic dot-blot hybridization.

PMID- 9760536
TI  - Detection and quantification of plant viruses by PCR.

PMID- 9760537
TI  - Assaying levels of virus with local lesion hosts.

PMID- 9760538
TI  - Field testing resistance of transgenic plants.

PMID- 9760539
TI  - Agronomic performance of transgenic plants.

PMID- 9760540
TI  - Mechanisms of resistance. Expression of coat protein.
AB  - Expression of viral CP genes in transgenic plants can lead to virus resistance by
      interference of either the transcript or the protein with virus infection.
      Dependence of resistance on CP accumulation can be most convincingly shown by
      comparison of plants that accumulate CP with plants that accumulate a
      nontranslatable CP transcript. Even in cases in which CP accumulation is
      required, the degree of resistance does not always correlate with CP levels in
      transgenic plants. In cases in which CPMR can be overcome by inoculation with
      viral RNA instead of virions, interference with virion disassembly is the likely
      cause of resistance. Classical crossprotection can also sometimes be overcome by
      RNA inoculation, and, in this case, appears to work by a similar mechanism. There
      is no evidence yet that CPMR is caused by a nonspecific plant defense response
      that might be triggered by the accumulating CP. Measurement of virus accumulation
      in protoplasts prepared from transgenic plants was used to show interference with
      early events of virus infection. There is no clear evidence yet for inhibition of
      local virus spread in transgenic plants. A reduced rate of virus accumulation in
      inoculated leaves can usually also be explained with reduced rate of replication.
      However, in the case of CPMR to CMV, it appears that early events, as well as
      systemic spread, are affected. Reduced vector transmission of virus infection
      from inoculated transgenic plants to nontransgenic plants has been observed. It
      is not known whether this is just a consequence of lower virus levels in the
      transgenic plants or whether direct interference with acquisition and
      transmission by the vector is also involved. In addition to virion formation, CP
      can function in different ways in plant virus infections. Replication, long
      distance spread, and vector transmission can also depend on the presence of CP.
      Expression of genes encoding nonfunctional CPs in transgenic plants can be tried
      in order to interfere with normal CP function. Knowledge of CP function(s) in a
      particular plant-virus interaction will be useful to design gene constructs.
      Since CP accumulation levels in transgenic plants do not always correlate with
      resistance, newly generated transgenic plant lines are now frequently tested for
      virus resistance before further characterization. However, if the objective of a
      transformation experiment is also to study the mechanism of CPMR, it is necessary
      to determine transcript and protein levels in the transgenic plants. Gene
      constructs encoding nontranslatable and antisense CP transcripts should be
      included in the experiment. If possible, transgenic plants should be inoculated
      with virions and viral nucleic acid, and replication in isolated protoplasts
      should be determined.

PMID- 9760541
TI  - Mechanisms of RNA-mediated resistance to plant viruses.

PMID- 9760542
TI  - Detection of risks associated with coat protein transgenics.

PMID- 9760543
TI  - Potential benefits of the transgenic control of plant viruses in the United
      Kingdom.

PMID- 9760544
TI  - [Vascular ischemic dementia].
AB  - Observations are reported of the course and other interrelations between clinical
      pattern and computer tomography results in 36 patients with vascular ischaemic
      dementia. Attention is called to the frequency of transient dementia-like
      disturbances following stroke and to the importance of the middle gyrus of the
      left frontal lobe in the development of dementia manifestations. In cases with
      slow progression of dementia symptoms and only scant neurological signs not
      infrequently long-standing improvement or even complete remission of dementia
      symptoms occur which sets them apart from mixed forms of dementia. The problem of
      the occurrence of isolated dementia syndromes of sudden onset is discussed and
      for them the term "stroke with dementia" is proposed.

PMID- 9760545
TI  - [Carotid artery disease in patients with ischemic stroke. Results of year-long
      observation conducted within the framework of prospective epidemiological
      studies, Warsaw, 1991-1992].
AB  - A cohort of 297 patients with ischaemic stroke were followed for one year.
      Doppler ultrasonography, done in 219 patients (109 women and 110 men), aged 68.0
      +/- 12.6, revealed a concomitant carotid artery occlusive disease (CAD) in 76
      patients (34.7%), 34 women and 42 men, aged 66.5 +/- 11.1, 45 of them had high
      grade stenosis (> 75%) or occlusion. Claudication, myocardial infarction and
      hypercholesterolaemia diagnosed before the onset of stroke was found more often
      in patients with CAD, 11.1%, 22.2% and 4.4% was versus 2.8%, 12.3% and 1.4% in
      patients without CAD. Prevalence of other stroke risk factors, hypertension,
      diabetes, angina in both groups of patients was similar. Severe stenosis or
      occlusion was diagnosed more often among men (58%) and among smokers (55%), in
      the group of patients without CAD than 48% and 42% respectively. The onset of
      stroke was preceded more often by TIA--24% in group with CAD, versus 17% in
      patients without CAD. Neurological state on admission, test by Stroke Severity
      Scale and Weakness Score according to SDB, was similar in both groups of patients
      but prognosis was worst among patients with CAD, 13.5% of them developed
      recurrent stroke versus 7% in group without CAD. In Kaplan-Meier analysis one
      year cumulative survival rates were lower in the group of the patients with
      severe stenosis or occlusion.

PMID- 9760546
TI  - [Clinical types of Guillain-Barre syndrome].
AB  - A detailed history and the results of the physical examination of seven patients
      with unusual and not typical Guillain-Barre syndrome were described. The patients
      presented various levels of lesions and some signs and symptoms were not typical
      of classic clinical features. The variety of the clinical picture suggests the
      damage of nervous system in many places and at various levels, not only in the
      peripheral nerves, but also in the central nervous system. The heterogeneity of
      aetiology and aetiopathogenesis and immunological individual patient's reaction
      probably is the cause of the involvement of different structures.

PMID- 9760547
TI  - [Facial hemispasm: modern views on the etiology, pathogenesis and treatment.
      Personal experience with botulinum A toxin treatment].
AB  - The authors present current opinions on the etiology and strategies of treatment
      of hemifacial spasm. In the vast majority of patients it is caused by compression
      of facial nerve by redundant loops of vertebral and basilar arteries and their
      branches. It was confirmed by neuroradiology imaging techniques and during
      surgical interventions. In recent years a new, non-invasive method of treatment
      has gained a wide approval--the local injections of botulinum toxin A into
      contracting muscles is a highly effective (90%) and safe method of treatment. Our
      own material (10 patients, 22 sessions) confirms it as well.

PMID- 9760548
TI  - [The assessment of lamotrigine effectiveness in patients with drug-resistant
      epilepsy].
AB  - The aim of the study was to evaluate the efficacy of lamotrigine (LTG, Lamictal)
      in patients with long-lasting epilepsy. The group of 11 patients, 4F, 7M aged 16
      45 years, mean 31.3 years was included in the study. Complex partial seizures and
      complex partial with sec. generalization ones occurred in 5 patients, only simple
      and complex partial seizures in 4 and in 2 cases we observed primary generalized
      nonconvulsive seizures. The mean seizure frequency was 20/month before LTG
      treatment. The mean duration of epilepsy was 20 years. Monotherapy with
      carbamazepine was used in 2 patients, 9 took 2 antiepileptic drugs. The time of
      investigation and treatment was 4 months with 3 control visits. During LTG
      treatment the number of conventional antiepileptic drugs was reduced in 7
      patients. The dose of the basic antiepileptic drug was not changed. We evaluated
      how LTG had influenced the frequency, severity and duration of seizures,
      patients' mental state and adverse events appearance. Good result of treatment-
      seizure frequency reduction at least 50%--was observed in 5 patients (45.5%),
      moderate--seizure frequency reduction below 50%--in 1 patient (9%), bad result-
      no change in seizure frequency or its increase--in 5 cases (45.5%). In 5 patients
      the drug influenced positively seizure severity and duration. Beneficial
      psychotropic effect of the drug was found in 2 patients with mental disturbances.
      Adverse effects occurred in 3 patients. They were vertigo and ataxia in 1
      patient, drowsiness in 1 case and dyspeptic symptoms in 1 patient. Adverse events
      were mild and transient in 2 patients. In 1 patient with vertigo and ataxia they
      resulted in the drug being discontinued after 3 month treatment. On the whole
      lamotrigine shows a positive influence on the frequency, severity and duration of
      seizures in some patients with therapy resistant epilepsy. The drug is well
      tolerated and seems to have positive psychotropic effects.

PMID- 9760549
TI  - [Hereditary sensorimotor neuropathy in electrophysiological studies].
AB  - We performed clinical and electrophysiological studies in 42 children with
      hereditary motor and sensory neuropathy type I and II (HMSN I and II) and in 103
      members of their families. In 24 families with HMSN I the conduction velocity and
      latency were markedly changed in the nerves innervating the distal muscles
      (median, peroneal nerves) as well as proximal muscles (facial, axillary and
      musculocutaneous nerves). The changes were uniform in all motor and sensory
      nerves studied in a particular patient. The intensity of changes was similar in
      members of their families even when the clinical abnormalities were minimal, thus
      the degree of conduction velocity slowing was uniform within families. In adults
      with HMSN I (group A i B) we found less marked slowing of nerve conduction as
      compared to children (group P), the difference being significant (p < 0.001). It
      may suggest a slow process of peripheral nerves maturation despite the existing
      morbid condition. In patients of 18 families with HMSN II slight changes in
      conduction velocity were found only in nerves innervating the distal muscles,
      more evident in legs (peroneal and sural nerves). Conduction time of facial,
      axillary and musculo-cutaneous nerves was normal. The values of nerve conduction
      were not changing with patients' age. We recommend examining conduction time in
      facial, axillary or musculocutaneous nerve as a useful procedure for
      differentiation between HMSN I and II, especially in families with borderline
      conduction values in the nerves innervating distal muscles.

PMID- 9760550
TI  - [Prognostic significance of transient hyperglycemia in acute phase of ischemic
      stroke].
AB  - Experimental studies of different stroke models equivocally showed that
      hyperglycaemia is responsible for the increase of infarct volume and mortality.
      Similar results were obtained in several, but not all clinical studies. The aim
      of the study was to assess the occurrence and prognosis of transient
      hyperglycaemia in non-diabetic, acute ischaemic stroke patients. A consecutive
      series of 204 patients admitted to the Stroke Unit within 48 hours after the
      onset of the first-ever hemispheric ischaemic stroke, confirmed by CT and/or
      autopsy, were included in the study. Blood samples for determination of glucose
      level were obtained immediately after admission, on the 1-st, 2-nd, 3-rd, 5-th, 7
      th and 14-th day of stroke. The fructosamine and HbA1 measurements were used to
      exclude patients with previous glucose intolerance. The severity of stroke was
      assessed according to Scandinavian Neurological Stroke Scale on admission, on the
      first, 7-th, 14-th and 30-th day of stroke. Transient hyperglycaemia, defined as
      at least one elevated glucose level in the first week of stroke with normal level
      of HbA1 and fructosamine was found in 65 (31.9%) of patients. Patients with
      transient hyperglycaemia did not differ from diabetics and normoglycaemic
      according to age, gender, history of hypertension and other risk factors. 30 day
      mortality in the group of patients with transient hyperglycaemia was
      significantly higher than in normoglycaemic ( p. < 0.001) and diabetic patients.
      Transient hyperglycaemic patients died earlier, mainly on the 7-th day after
      admission whereas patients with normoglycaemia died mainly on the 18-th day (p <
      0.0001). The main reason of death in hyperglycaemic patients were cardiac
      complications (15/20), in normoglycaemic--the consequences of immobility (8/11)
      (< 0.01). The results of our study showed that the transient hyperglycaemia
      occurred in about one third of acute ischaemic stroke patients and resulted in
      higher 30-day mortality.

PMID- 9760551
TI  - [The usefulness of intraoperative high-frequency doppler flowmetry in surgeries
      for intracranial aneurysms].
AB  - The flowmeter enables estimation of blood flow velocity changes in small calibre
      arteries. The authors examined blood flow velocity patterns in the vessels during
      aneurysm operations and blood flow velocity and its disturbances inside aneurysm.
      Evaluation technique, technical data of the flowmeter use are described and the
      characteristics of the blood flow velocity picture in cerebral arteries obtained
      by this method is presented. The presented method enables a very precise
      estimation of blood flow velocity and detection of changes in flow patterns. The
      method may become very helpful in identification of the vessels in other types of
      cerebral surgery.

PMID- 9760552
TI  - [The study of the role of intervertebral disc neovascularization and immune
      response in the pathogenesis of lumbar discopathy].
AB  - In adult humans moral intervertebral disc (id) is an avascular tissue and becomes
      so called sequestrated autoantigen. Any acquired defect of anulus fibrosus may
      potentially lead to contact of immunocompetent cells circulating in the blood
      with id antigens thus inducing autoimmune reaction. 34 patients operated on
      because of lumbar discopathy were studied. The id injury was divided into: a)
      protrusion, B) simple prolapse, c) subligamentous prolapse, d) sequester. The
      samples of surgically removed id were subjected to histopathological and
      immunohistochemical study. Presence of granulation tissue, neovascularization and
      humoral response (confirmed by immunopositive reaction to factor VIII and IgG)
      was found in decreasing pattern in the following groups: I) sequesters, 2) simple
      prolapses, and 3) subligamentous prolapses. Among protrusions there were only two
      cases positive for IgG. A negative reaction to C3bR was seen in all the groups of
      id. The obtained results suggest that immune reaction against lumbar id is rather
      an effect than a cause of its herniation.

PMID- 9760553
TI  - [Sleep apnea syndrome in acromegalic patients].
AB  - The aim of this report was to analyse the sleep apnea rate and its clinical
      picture in acromegaly patients before and after the surgical treatment. The
      authors investigated both hormones levels and spirometric coefficients. They
      found, that surgical removal of microadenoma from transphenoidal approach led to
      the fast regression of the syndrome.

PMID- 9760554
TI  - [Enzymatic activity in cerebrospinal fluid in the monitoring of the brain lesions
      following intracranial tumors].
AB  - After intracranial tumour surgery edema, ischaemic and haemorrhagic changes are
      developing in the brain. It causes leakage of certain intracellular components
      and enzymes into extracellular and cerebrospinal fluid. This study includes 46
      patients operated on for cerebral tumours. Lumbar CSF was obtained in
      postoperative course and the activity of AST, ALT, LDH, alpha HBDH, CK, gamma GT
      and oxygen concentration were estimated. In the control group were 10 patients
      suffering from sciatic pain and CSF was obtained during radiculography. For
      diagnostic and prognostic purposes of biochemical markers statistical analyse
      methods were employed and comparisons with clinical factors were carried out. In
      conclusions we suggest that enzymes AST, alpha HBDH, CK and oxygen content give
      valuable additional information of postoperative brain damage.

PMID- 9760555
TI  - [Modern views on the pathogenesis of Wilson's disease].
AB  - Wilson's disease is a rare, multiorganic genetically coded disorder, induced by
      impaired copper transport. The recent identification of the disease gene and the
      discovery of gene product--copper transporting P-type ATPase that is integrate
      membranous protein has contributed greatly to better understanding of the
      pathogenesis. This protein is probably essential for incorporation of copper into
      ceruloplasmin and for its biliary excretion. Multiple mutations of Wilson's
      disease gene are responsible for the excess of so called "free" copper which is
      toxic to tissues. Copper toxicity involves first of all, functional disorders of
      many enzymatic systems, particularly those of respiratory chain enzymes. In the
      central nervous system, a special kind of copper toxicity is medicated by
      astroglia, so that a direct, harmful effect of both copper and ammonia on the
      brain is observed. The authors present a current review on biochemical mechanisms
      of copper toxicity and physiopathological significance of the CNS astroglia in
      Wilson's disease.

PMID- 9760556
TI  - [The role of protein C in the pathogenesis of stroke].
AB  - This paper presents the role of inhibitory protein C in the haemostatic
      processes, types of its deficiency and current opinions concerning the role of
      protein C deficiency in the pathogenesis of stroke. Deficiency of protein C (PC)
      or activated protein C resistance (both hereditary and acquired) play a role in
      pathogenesis of stroke, but not so great as it was thought until quite lately.
      Isolated protein C deficiency in old patients does not increase the risk of
      stroke. But in children hereditary deficiency of PC or activated PC resistance
      are of great importance in pathogenesis of ischaemic or venous stroke. In the
      presence of additional risk factors both in children and in adults deficiency of
      PC may be an important condition leading to stroke occurrence.

PMID- 9760557
TI  - [Severe meningoencephalitis in Borrelia burgdorferi infection].
AB  - We present a case of borreliosis with severe impairment of central nervous
      system. The patient a 43-year-old man, presented with neurological signs and
      symptoms and severe psychiatric disorders. The diagnosis was established several
      months after the onset of neurological signs. CSF examination revealed lymphocyte
      pleocytosis and specific antibodies against B. burgdorferi in high titres. MRI of
      the brain showed inflammatory lesions. Due to the treatment with antibiotics,
      patient's state improved and pleocytosis in CSF disappeared. However, after 1-
      year follow-up, specific antibodies were still present in high titres. Clinical
      manifestations and the results of diagnostic procedures show multifocal
      encephalitis in the acute phase of the disease and encephalopathy as a residual
      syndrome.

PMID- 9760558
TI  - [Abdominal migraine in adults].
AB  - A case of a 35-year-old woman with abdominal migraine is presented. For four
      years she had been suffering from abdominal pains occurring only at night, always
      between 1 and 3 a.m. The patient always woke with abdominal pains and nausea.
      Each time she had diarrhoea and vomited and found that this gave her relief from
      the pain. Sometimes she lost consciousness for 1-2 minutes. After the attack she
      felt very weak, her legs and feet became numb and she found it difficult to get
      to sleep. The attacks and the fainting fits increased in frequency until she had
      several a month. Numerous gastrological examinations did not reveal any
      deviations from the normal. At the anti- epileptic consulting unit, abdominal
      epilepsy was excluded (no abnormalities were found in the eeg and CT examinations
      of the cranium). As a child she had paroxysmal abdominal pains. When the patient
      was 10 years old, she had an attack lasting one week and though the pain was
      severe on the left side, appendectomy was performed. Her mother suffers from
      migraine with very severe head pains. The patient was referred to our consulting
      unit where she was treated with Pizotifen in doses of 0.5 mg morning and noon and
      1 mg in the evening for three months during which time she had no attacks. A few
      weeks after discontinuing this treatment, the nocturnal attacks again occurred
      though the pains were not so severe. She was then prescribed Nitrendipine, 5 mg
      nightly, and the attacks ceased. However, the patient said that she had felt
      better when taking Pizotifen.

PMID- 9760559
TI  - [Diagnostic difficulties in a case of multifocal changes in the brain in
      computerized tomography and in magnetic resonance imaging].
AB  - This paper presents a case of multifocal metastases in the brain, which on the
      basis of typical imaging magnetic resonance and computerized tomography suggested
      possible parasitic changes (cerebral cysticercosis). On the basis of these
      pictures cerebral cysticercosis was diagnosed, in spite in the absence of
      serologic changes in blood and cerebrospinal fluid. The lack of improvement after
      anticysticercosis drugs, the further course of the disease as well as new foci
      located in other organs outside the brain, allowed to recognize numerous
      metastases in the brain although until the end of the clinical observation the
      primary lesion of the neoplasm was not found. The histopathological examination
      of samples of brain tissue confirmed the diagnosis of numerous metastases of
      poorly differentiated carcinoma.

PMID- 9760560
TI  - [Subarachnoid hemorrhage due to conus medullaris ependymoma].
AB  - A case of conus medullaris tumour (ependymoma) is reported in which the
      presenting symptom was subarachnoid haemorrhage, which has left bladder
      dysfunction. 70-year-old patient was admitted to the Department of Neurology due
      to symptoms of conus medullaris lesion with retention of urine and diminished
      pain sensitivity in perianal zona. He had been hospitalized 30 years ago due to
      vomiting, headache and pain in lumbar region. The cerebrospinal fluid examination
      confirmed the diagnosis of subarachnoid haemorrhage. Cerebral angiography failed
      to show the source of bleeding. Myelography and spinal arteriography showed nor
      tumour neither vascular malformation. Only MRI examination performed after 30
      years following the first symptoms of tumour made possible the correct diagnosis-
      tumour in vertebral canal at L1-L2 level compressing conus medullaris. Surgical
      procedure confirmed the diagnosis. Histopathological examination--ependymoma
      myxopapillare.

PMID- 9760561
TI  - [Endoscopic brain surgery of intracranial cysts: report of 2 cases].
AB  - Two cases are presented of intracranial cystic lesions, which were treated by the
      neuroendoscopic method. In the two cases the patients' radiological and clinical
      conditions improved. Neuroendoscopy is a very effective and safe method to treat
      intracranial cystic lesions.

PMID- 9760562
TI  - [A case of schizophrenia-like psychosis in a patient with arachnoid cyst].
AB  - The aim of this report was the presentation of the extremely rare case of the
      arachnoid cyst of the brain, with only psychiatric manifestation. According to
      the literature and own experience the authors conclude, that the treatment of
      these patients would be interdisciplinary, both neurosurgical and psychiatric.

PMID- 9760563
TI  - [Response to the letter by Ewa Nachman, Mark Nachman and Halina Zblowska on the
      paper "A contribution to the microanatomy of the initial segment of the long
      middle artery (Heubner's)" published in Neurol. Neurosurg. Pol., 1997, 31, 4,
      727...].

PMID- 9760564
TI  - [Letter concerning the paper by Stefan Bayassi and Stefan Kopczynski: "Traumatic
      intracranial hematomas: analysis of 54 cases" published in Neurol. Neurosurg.
      Pol., 1997, 31, 4, 727...].

PMID- 9760565
TI  - [Report on the congress on treatment and studies on multiple sclerosis, Istambul
      (Turkey), Nov. 2-5, 1997].

PMID- 9760566
TI  - [Report on the First training course of the Stroke Association of the Central
      East Europe in Prague, Dec. 3-7, 1997].

PMID- 9760567
TI  - Immunological tolerance. Introduction.

PMID- 9760568
TI  - Mechanisms of peripheral T cell tolerance.
AB  - Peripheral tolerance to self proteins is induced because these antigens are
      presented to T lymphocytes under conditions that do not allow effective immune
      responses to develop, or because the responses of the specific T cells are
      tightly regulated. The two principal mechanisms of peripheral tolerance are
      activation-induced cell death (AICD) and anergy. In CD4+ T lymphocytes, AICD is
      induced by repeated stimulation, with high levels of interleukin (IL)-2
      production. Under these conditions, the T cells co-express Fas (CD95) and Fas
      ligand (FasL), and engagement of Fas triggers apoptotic death of the T cells.
      Mice with defects in Fas, FasL, IL-2R alpha or beta chain exhibit defects in AICD
      and develop autoimmune disease. The induction of T cell anergy is dependent on
      the recognition of B7 co-stimulators by the inhibitory T cell counter-receptor,
      CTLA-4. Failure of anergy is the likely basis for the fatal autoimmune disease of
      CTLA-4 knockout mice. The single-gene defects that result in autoimmunity are all
      defects in lymphocyte regulation, indicating that tolerance is often maintained
      by the control of lymphocyte responses to self antigen. The existence of distinct
      pathways of T cell tolerance suggest that different types of antigens induce
      tolerance by distinct mechanisms.

PMID- 9760569
TI  - B cell antigen receptor signalling in the balance of tolerance and immunity.
AB  - The quantity and quality of signals from the B cell antigen receptor (BCR) drives
      the positive and negative selection of B lymphocytes and establishes the balance
      of tolerance and immunity. Experiments using immunoglobulin transgenic mice and
      mutations in key BCR signalling components have given insight into how the
      antigen receptor is tuned and how thresholds for qualitatively different outcomes
      are established and maintained. This research also describes how genetic variants
      can shift the balance between autoimmunity and tolerance.

PMID- 9760570
TI  - The study of self-tolerance using murine haemoglobin as a model self antigen.
AB  - T cell tolerance to self proteins involves both thymic and peripheral mechanisms.
      We have used allotypic differences in murine haemoglobin (Hb) to study the
      development of tolerance to the abundantly expressed self-protein. In Hb beta s/H
      2k mice, the response to Hb beta d is directed against Hb beta d (64-76)
      presented by I-Ek molecules. Using T cell hybridomas and clones specific for this
      epitope, we have demonstrated that Hb(64-76)/I-Ek complexes and present on
      antigen-presenting cells in all lymphoid organs including dendritic cells, B
      cells and macrophages. In the thymus, the presence of these complexes results in
      negative selection of transgenic T cells with high levels of Hb(64-76)/I-Ek
      specific receptor. However, cells with intermediate levels of specific receptor
      escape negative selection and can be found in the periphery. Under normal
      circumstances these cells remain tolerant, but can be activated by mechanisms
      which increase the number of Hb(64-76)/I-Ek complexes.

PMID- 9760571
TI  - Tolerance and determinant hierarchy.
AB  - The overall T cell response to a multideterminant antigen consists of the sum of
      responses to a limited number of different determinants on the protein. Antigen
      presenting cells (APCs) are crucial in delimiting the determinants on the protein
      to which a response will be mounted. This influence is apparent at two levels.
      First, the determinants that are generated and displayed by APCs in the thymus
      are pivotal in shaping the T cell repertoire that will be available for
      responding to antigen determinants in the periphery. Second, antigen processing
      affects the selection of determinants that become displayed by the various
      peripheral APC populations that are involved in inducing and promoting a T cell
      response. We have studied the effect of the display hierarchy on tolerance
      induction to individual determinants in transgenic mice expressing different
      serum levels of hen egg lysozyme. We have also analysed aspects of the processing
      machinery that contribute to shaping the hierarchy of determinant display on MHC
      class II molecules: proteolysis and reduction of disulfide bonds.

PMID- 9760572
TI  - Molecular genetic studies in lymphocyte apoptosis and human autoimmunity.
AB  - Using a genetic approach, we have studied the molecular basis of human
      autoimmunity with special emphasis on a disease that is due to defective
      lymphocyte apoptosis. Recently, we and our collaborators have found that the
      autoimmune/lymphoproliferative syndrome (ALPS), an inherited disease of children
      comprising marked lymphoid hyperplasia and autoimmune manifestations, is due to
      abnormalities in the CD95 gene that cause defective lymphocyte apoptosis. Our
      recent investigations have shown that the mutations in most families with ALPS
      cause either global or local changes in the structure of a cytoplasmic portion of
      the molecule called the 'death domain'. These death domain alterations impair
      binding of the adapter protein FADD/MORT1 and result in a failure to activate
      apoptotic caspases after CD95 (Fas/APO-1) cross-linking. Mutations in apoptotic
      caspases may also contribute to the pathogenesis of ALPS in individuals that have
      no CD95 gene mutations.

PMID- 9760573
TI  - A role for CTLA-4-mediated inhibitory signals in peripheral T cell tolerance?
AB  - Occupancy of the antigen receptor is not sufficient for activation of naive T
      cells--additional co-stimulatory signals are required that can be provided only
      by 'professional' antigen-presenting cells. This two-signal model for T cell
      activation has been thought to provide a mechanism for the induction and
      maintenance of peripheral tolerance. Work over the past six years has
      demonstrated that the relevant co-stimulatory receptor on T cells is the molecule
      CD28. Recent data shows that the CD28 homologue CTLA-4 plays a role in negative
      regulation of T cell responses. Here we suggest that CTLA-4 may also serve as an
      attenuator of T cell-activating signals, raising the threshold of stimulation
      required to obtain full activation. The inhibitory signals mediated by CTLA-4 may
      provide an additional mechanism for the maintenance of peripheral tolerance.

PMID- 9760574
TI  - Antigen-specific CD4+ T cells that survive after the induction of peripheral
      tolerance possess an intrinsic lymphokine production defect.
AB  - Injection of soluble foreign antigen without an adjuvant induces a state of
      antigen-specific immunological unresponsiveness. We investigated the cellular
      mechanisms that underlie this form of peripheral tolerance by physically tracking
      a small population of ovalbumin (OVA) peptide/I-Ad-specific, CD4+ T cell receptor
      (TCR) transgenic T cells following adoptive transfer into normal recipients.
      Injection of OVA peptide in the absence of adjuvant caused the antigen-specific T
      cells to proliferate for a brief period after which most of the T cells
      disappeared. The remaining OVA-specific T cells had converted to a memory
      phenotype but were poorly responsive in vivo as evidenced by a failure to
      accumulate in the draining lymph nodes following immunization with OVA peptide in
      adjuvant. These surviving T cells possessed a long-lasting, but reversible,
      defect in Il-2 and TNF-alpha production and in vivo proliferation, but did not
      gain capacity to produce Th2-type cytokines or suppress the clonal expansion of T
      cells specific for another antigen. Therefore, some antigen-specific T cells
      survive this peripheral tolerance protocol but are functionally unresponsive due
      to an intrinsic activation defect.

PMID- 9760575
TI  - Antigen-specific tolerance induction and the immunotherapy of experimental
      autoimmune disease.
AB  - Antigen-specific tolerance induction is the ultimate goal for specific
      immunotherapy of autoimmune diseases. Here we will discuss recent experiments
      designed to induce tolerance following mucosal administration of antigens in a
      mouse model of experimental autoimmune encephalomyelitis (EAE). We were unable to
      induce oral tolerance either with whole myelin, myelin basic protein (MBP) or the
      immunodominant peptide antigen. Oral tolerance was possible, however, with an
      analogue of the immunodominant peptide modified to increase its affinity for the
      restricting major histocompatibility complex (MHC) antigen. By contrast,
      intranasal deposition of peptide antigen proved highly effective for both
      prevention and treatment of EAE. Prevention of disease was directly related to
      the antigenic property of the peptide which, in itself, was related to affinity
      for MHC. Notably, administration of a single peptide was shown to inhibit disease
      involving multiple epitopes. We investigated the resulting bystander regulation
      by studying the cellular basis of peripheral tolerance in a transgenic model.
      These studies indicate that bystander regulation may be the consequence of
      selective cytokine secretion.

PMID- 9760576
TI  - Quantitative and qualitative control of antigen receptor signalling in tolerant B
      lymphocytes.
AB  - Lymphocyte antigen receptors, such as the B cell antigen receptor (BCR), have the
      ability to promote or inhibit immune responses. This functional plasticity is
      exemplified by BCR-induced mitosis in naive but not tolerant B cells and is
      correlated with biochemical differences in the signals triggered by foreign and
      self antigens. Acute stimulation of naive B cells with foreign antigen induces a
      biphasic Ca2+ flux, and activates nuclear signalling through NF-AT, NF-kappa B,
      JNK and ERK. In tolerant B lymphocytes, by contrast, self antigen triggers only a
      low Ca2+ plateau, NF-AT and ERK. After removal from self antigen, the BCRs on
      tolerant B cells reacquire the ability to stimulate a biphasic Ca2+ flux and to
      promote proliferation. The differences in nuclear signalling between naive and
      tolerant cells is brought about in part by differences in the magnitude of the
      Ca2+ signal. A low, sustained Ca2+ signal, such as that seen in tolerant B cells,
      activates NF-AT, whereas, a high but transient Ca2+ spike, which resembles that
      triggered in naive B cells, activates NF-kappa B and JNK. These findings
      demonstrate that the quantitative differences in Ca2+ signalling between naive
      and tolerant B cells are reversible and contribute to the differential triggering
      of nuclear signals. The activation of selected transcription factors may in turn
      account for the different functional responses triggered in naive and tolerant
      lymphocytes.

PMID- 9760577
TI  - Tolerance induction with CD4 monoclonal antibodies.
AB  - One of the major goals of therapeutic immunosuppression is to be able to use
      short-term therapy to achieve long-term tolerance. Short courses of CD4
      antibodies are able to create peripheral tolerance in a mature immune system. The
      resulting tolerant state shows evidence of being dominant in that one can observe
      the features of linked suppression, transferable suppression and infectious
      tolerance in a variety of model systems. Only in the situation of administration
      of high doses of marrow could one find evidence of central and peripheral
      tolerance which had all the features of being deletional rather than regulatory.
      These findings suggest that attaining dominant tolerance and linked suppression
      may be the least invasive of all tolerance-inducing strategies for clinical
      application.

PMID- 9760578
TI  - A two-step model for the induction of organ-specific autoimmunity.
AB  - Peripheral tolerance is considered to be a safeguard against autoimmunity but the
      mere existence of anergic T cells renders them potentially dangerous. Using
      transgenic mice that were tolerant to a foreign MHC class I antigen (Kb)
      exclusively expressed in the liver, we investigated whether reversal of tolerance
      in vivo would directly result in autoimmunity. Breaking of tolerance was achieved
      by application of tumour cells expressing both Kb and interleukin 2. Despite the
      fact that the respective mice were now able to reject Kb-positive grafts, the
      reversed T cells did not infiltrate and attack the Kb-positive liver. However,
      when the liver was 'conditioned' through an inflammatory reaction either by
      irradiation or by infection with Listeria, massive T cell infiltration and liver
      damage were observed in the reversed mice. The results show that at least two
      steps are required for autoimmunity: (1) activation of antigen-specific T cells,
      and (2) conditioning of the target organ. It will be important to determine the
      factors leading to conditioning but it is likely that adhesion molecules are
      involved. These experiments are not only of relevance for treatment of autoimmune
      disease but also for tumour therapy.

PMID- 9760579
TI  - Cross-presentation of self antigens to CD8+ T cells: the balance between
      tolerance and autoimmunity.
AB  - Upon encounter with foreign antigen, tissue-associated antigen-presenting cells
      (APCs) migrate to draining lymph nodes to prime specific T cells. Using the
      transgenic RIP-mOVA model, we recently demonstrated that self antigens derived
      from peripheral tissues are constitutively transported to draining lymph nodes,
      and can be presented in association with MHC class I molecules by a bone marrow
      derived APC population. This form of class I-restricted presentation of exogenous
      antigen has been referred to as cross-presentation and can induce activation and
      proliferation of antigen-specific CD8+ T cells. In the absence of CD4+ T cell
      help, activation of CD8+ T cells is inefficient, and cross-presentation leads to
      peripheral deletion of autoreactive CD8+ T cells, acting as a mechanism to
      maintain self-tolerance. If CD4+ T cell help is available, CD8+ T cell responses
      to self antigens can be rendered immunogenic, leading to autoreactive responses.
      Whether autoimmunity results from such responses also depends on the tissue
      location of the antigen. In RIP-mOVA mice, which express the model antigen mOVA
      (a membrane-bound form of ovalbumin) in the pancreatic beta cells and kidney
      proximal tubules, OVA-specific CD8+ T cells, activated by cross-presentation,
      infiltrated the pancreas and caused B cell destruction. Interestingly, however,
      these cells did not infiltrate the kidney, suggesting that proximal tubular cells
      are to some extent protected from immune destruction. Analysis of the role of
      antigen concentration indicates that high doses were required for efficient cross
      presentation, suggesting that this pathway is directed towards immune responses
      to high-dose antigens, such as may be present during viral infection.

PMID- 9760580
TI  - Tolerance induction in mature T lymphocytes.
AB  - T lymphocytes with self-destructive capacity are often found in healthy
      individuals, indicating efficient control mechanisms that prevent autoimmunity.
      Recently, we were able to demonstrate the existence of peripheral tolerance in
      double-transgenic mice expressing the foreign histocompatibility antigen H-2Kb
      exclusively outside the thymus and a T cell receptor (Des.TCR) directed against
      the Kb molecule. In mice expressing Kb only on keratinocytes anti-Kb T cells were
      still present but failed to reject Kb-positive tissue grafts. This observation
      would imply a continuous migration of naive T cells exported from the thymus into
      non-lymphoid tissues where these fresh thymic emigrants would need to be
      tolerized. However, this is in contrast to the view that migration to peripheral
      tissues is restricted to activated T cells. To investigate whether there is a
      continuous process of tolerization of naive T cells in adult DES.TCR x 2.4Ker-Kb
      mice, 2.4Ker-Kb mice were crossed with Rag-2-deficient mice and reconstituted
      with bone marrow cells of Des.TCR transgenic mice (Des.TCR x 2.4Ker-Kb.Rag-2-).
      Tolerance was not observed in these chimeric mice. We conclude from these results
      that in contrast to the neonate the adult physiological environment does not
      allow tolerance induction to antigens expressed on keratinocytes in T cells newly
      exported from the thymus. Furthermore, we have to postulate regulatory events
      responsible for the maintenance of peripheral tolerance in the adult Des.TCR x
      2.4Ker-Kb animals.

PMID- 9760581
TI  - T lymphocyte-mediated control of autoimmunity.
AB  - Autoreactive T cells can be readily identified in the peripheral lymphocyte pool
      of both humans and experimental animals. Peripheral tolerance may be maintained
      by regulatory/suppressor T cells which prevent the activation of autoantigen
      specific cells. Mice thymectomized on day 3 of life (d3Tx) develop a wide
      spectrum of organ-specific autoimmune diseases. Reconstitution of d3Tx mice with
      CD4+ CD25+ T cells from normal mice prevents the development of disease.
      Similarly, CD4+ CD25+ T cells prevent the transfer of disease by autoantigen
      specific cloned T cells derived from d3Tx mice. Thus, regulatory T cells can
      prevent both the induction and effector function of autoreactive T cells. In
      vitro, the CD4+ CD25+ population is anergic to stimulation through the T cell
      receptor (TCR) and suppresses the proliferative responses of normal CD4+ CD25-
      cells by a contract-dependent mechanism. Suppression is not MHC-dependent, but
      requires activation of the CD4+ CD25+ population. The mechanism of suppression in
      vivo and the target antigen(s) of this unique regulatory population remain to be
      characterized.

PMID- 9760582
TI  - Resting energy expenditure and nitrogen balance in critically ill pediatric
      patients on mechanical ventilation.
AB  - Nutritional support is important in critically ill patients, with variable energy
      and nitrogen requirements (e.g., sepsis, trauma, postsurgical state) in this
      population. This study investigates how age, severity of illness, and mechanical
      ventilation are related to resting energy expenditure (REE) and nitrogen balance.
      Nineteen critically ill children (mean age, 8 +/- 6 [SD] y and range 0.4-17.0 y)
      receiving total parenteral nutrition (TPN) were enrolled. We used indirect
      calorimetry to measure REE. Expected energy requirements (EER) were obtained from
      Talbot tables. Pediatric Risk of Mortality (PRISM) and Therapeutic Intervention
      Scoring System (TISS) score were calculated. Total urinary nitrogen was measured
      using the Kjeldahl method. PRISM and TISS scores were 9 +/- 5 and 31 +/- 6
      points, respectively. REE was 62 +/- 25 kcal.kg-1.d-1, EER was 42 +/- 11 kcal.kg
      1. d-1, and caloric intake was 49 +/- 22 kcal.kg-1.d-1. Nitrogen intake was 279
      +/- 125 mg.kg-1.d-1, total urinary nitrogen was 324 +/- 133 mg.kg-1.d-1, and
      nitrogen balance was -120 +/- 153 mg.kg-1.d-1. The protein requirement in this
      population was approximately 2.8 g.kg-1.d-1. These critically ill children were
      hypermetabolic, with REE 48% higher (20 kcal.kg-1.d-1) than expected. Nitrogen
      balance significantly correlated with caloric and protein intake, urinary
      nitrogen, and age, but not with severity of illness scores or ventilatory
      parameters.

PMID- 9760583
TI  - Lifestyle factors fail to explain the variation in plasma leptin concentrations
      in women.
AB  - To assess the relationship between circulating leptin concentrations, metabolic
      parameters, and lifestyle factors such as alcohol intake, physical activity
      level, smoking habits, and reproductive history, a cohort of 359 women was drawn
      from a population-based study conducted in Victoria, Australia. The parameters
      measured included body mass index (BMI); waist and hip circumference; blood
      pressure; and fasting glucose, insulin, triacylglycerol, cholesterol, and leptin
      concentrations. In addition, a self-administered questionnaire was used to assess
      reproductive history, physical activity level, alcohol intake, and smoking
      habits. Our results demonstrated that BMI, body weight, waist circumference, and
      hip circumference were all strongly correlated with circulating leptin
      concentrations in this population (r > 0.56, P < 0.001 in all cases). Waist/hip
      ratio, triacylglycerols, insulin, glucose, and cholesterol were also associated
      with leptin (P < 0.05), but there was no association between leptin and age,
      height, or blood pressure. When these associations were adjusted for BMI, age,
      glucose, and waist circumference were significantly associated with leptin. The
      lifestyle factors examined did not help to explain the observed variation in
      leptin concentrations between individuals when results were adjusted for degree
      of adiposity and age.

PMID- 9760584
TI  - Bioelectrical impedance analysis in human immunodeficiency virus-infected
      patients: comparison of single frequency with multifrequency, spectroscopy, and
      other novel approaches.
AB  - Bioelectrical impedance (BIA), a prediction method for estimating body water
      compartments and body cell mass (BCM), is being increasingly used in studies of
      human immunodeficiency virus (HIV)-related wasting, but there are few validation
      studies of the method in this group. The aim of this study is to examine the
      relationship between impedance measurements and body water compartments in
      patients with advanced HIV disease, and to investigate whether the newer
      approaches of multifrequency BIA, BIA spectroscopy, logarithmic transformation
      using a parallel circuit model, and direct calculation from electrical theory
      offer any advantage over traditional single-frequency BIA. We measured total body
      water (TBW) by deuterium dilution and extracellular water by bromide dilution in
      33 patients with advanced HIV disease. Intracellular water and BCM were
      calculated from these results. Impedance was measured over a range of frequencies
      using a multifrequency analyzer. The relationship between impedance index at
      various frequencies and body water compartments was assessed by correlation and
      linear regression. We found that impedance index at higher frequencies had a
      closer relationship to TBW (r = 0.86, standard error of the estimate [SEE] = 2.96
      at 1000 kHz) and at lower frequencies a closer relationship to extracellular
      water (ECW) (r = 0.47, SEE = 3.13 at 0 kHz) than the traditional 50 kHz
      measurement (r = 0.84, SE = 3.11 for TBW; r = 0.44 SEE = 3.19 for ECW), but the
      differences were marginal and not statistically significant. None of the other
      novel approaches tested were significantly better than traditional single
      frequency measurement. The 50 kHz equation for BCM developed in this study [BCM
      (kg) = (0.360331 x Ht2/Z50) + (0.151123 x Wt)-2.95] may be useful to
      investigators using BIA for hIV-wasting studies.

PMID- 9760585
TI  - Total parenteral nutrition supplemented with medium-chain triacylglycerols
      prevents atrophy of the intestinal mucosa in septic rats.
AB  - Total parenteral nutrition (TPN) is associated with an increased incidence of
      bacterial translocation (BT) compared with enteral nutrition because of the
      disuse atrophy of the intestine. In this study, we assessed the effect of adding
      medium-chain triacylglycerols (MCT) to TPN for the prevention of mucosal atrophy
      in the intestine. Rats were subjected to either fat-free TPN, TPN with long-chain
      triacylglycerols (LCT), or TPN with MCT for 5 d and nutrition parameters were
      evaluated. In another set of rats receiving the same TPN regimen, 0.8 or 0.05
      mg/kg endotoxin was administered on day 4. Survival was evaluated and BT to the
      mesenteric lymph nodes, liver, and systemic blood was measured 24 h later. The
      mucosal heights of the jejunum and ileum were evaluated concurrently. The
      survival rate was significantly improved in the MCT group (P < 0.05) at the
      endotoxin dose of 0.8 mg/kg. The nutrition condition presented by phospholipid,
      total cholesterol, and total ketone body levels was the best in the MCT group
      compared to the other groups. The intestinal villous height in the ileum was
      significantly greater in the MCT group. However, the improvement of BT in MCT
      group was not statistically significant. In this endotoxin-challenged rat model,
      survival rate was improved by the supplementation of MCT. This effect may be
      presented in some part by the improvement in nutrition condition and by the
      prevention of mucosal atrophy in the intestine.

PMID- 9760586
TI  - Automated, eight-cage indirect calorimetry in rats.
AB  - We have constructed an automated, eight-cage indirect calorimeter (AIC) for the
      measurement of energy expenditure in rats. We compared the measurements of
      resting energy expenditure (REE) in rats during a 30-h fast obtained with the AIC
      with those obtained with a manual indirect calorimetry (MIC) system. There was
      both a high degree of correlation between the two techniques during the initial
      18 h of the fast (r = 0.90, P < 0.05) and strong intertechnique agreement. REE
      (AIC) decreased during the final 12 h of the 30-h fast (79.6 +/- 2.7-72.0 +/- 4.4
      kcal.kg-0.75.d-1 [mean +/- SD, P < 0.01]). REE (MIC) did not show a significant
      decrease during this part of the fast (79.7 +/- 2.6 - 75.2 +/- 4.7 kcal.kg-0.75.d
      1 [P = NS]). During the final 12 h of the fast agreement between the two systems
      gradually dissipated and correlation was poor (r = 0.375, P < 0.05). The
      frequency of animal handling necessitated by MIC may have resulted in a stress
      induced increase in metabolic work that would mask the animals' adaptive response
      to starvation. This investigation demonstrates the advantages of the AIC and
      calls into question the accuracy of manual methods under long-term starvation
      conditions.

PMID- 9760587
TI  - Alterations in N-acetylation of 3-methylhistidine in endotoxemic parenterally fed
      rats.
AB  - N-methylhistidine (3-meH) is endogenously released during muscle catabolism and
      serves as a marker of protein turnover. In rats > 85% of 3-meH is excreted in the
      urine as the N-acetyl derivative. It has been reported that the percent of non
      acetylated 3-meH (NA-3-meH) varies minimally with stress. To further evaluate
      these reports we randomized 39 male Sprague-Dawley rats (157-213 g) to receive
      parenteral nutrition only (PN) or PN plus continuous infusion of Escherichia coli
      026:B6 lipopolysaccharide at 6 (LPS-6) or 12 (LPS-12) mg.kg-1.d-1 for 48 h. All
      animals received isocaloric and isonitrogenous PN 24 h before and throughout the
      study with water ad libitum. Total 3-meH excretion was significantly increased (P
      < 0.05) in the LPS-6 (470 +/- 136 micrograms/48 h) and LPS-12 (557 +/- 171
      micrograms/48 h) groups versus the PN (331 +/- 126 micrograms/48 h) group. NA-3
      meH differed significantly between the LPS-12 (218 /+- 89 micrograms/48 h, LPS-6
      (94 +/- 48 micrograms/48 h), and PN (39 +/- 12 micrograms/48 h) groups (P <
      0.05). Percent NA-3-meH increased significantly from 12.7 +/- 3.9% in the PN
      group to 19.8 +/- 8.0 and 39.9 +/- 12.8% in the LPS-6 and LPS-12 groups,
      respectively (P < 0.05). No significant changes in acetyl 3-meH were found
      between groups. These data suggest that either saturation or inhibition of
      acetylation pathways occurs with increasing levels of stress. Due to the
      disproportionate increases in NA-3-meH and percent NA-3-meH during endotoxemia,
      only total 3-meH should be used as an indicator of protein turnover in rats.

PMID- 9760588
TI  - Bioactivation of the proximal food mutagen 2-hydroxyamino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (N-OH-PhIP) to DNA-binding species by human mammary
      gland enzymes.
AB  - We have investigated phase II activation of the food-derived mutagen 2
      hydroxyamino-1-methyl-6-phenyl[4,5-b]pyridine (N-OH-PhIP) by cytosolic
      acetyltransferase, sulfotransferase, and tRNA synthetase/kinase enzymes from
      human breast tissue. Cytosol from homogenates of mammary gland tissue obtained
      from breast-reduction surgery or mastectomy was incubated with and without enzyme
      specific cofactors, and mutagen binding of calf thymus DNA was quantified by 32P
      postlabeling. In addition, microsomal fractions of mammary epithelial cells from
      some individuals were examined for prostaglandin H synthetase activation of N-OH
      PhIP. Our results show that all four enzymes can participate in activating N-OH
      PhIP, thus inducing PhIP-DNA adduct formation in human mammary cells. However,
      not all individuals exhibited all these activities; instead each individual
      showed a combination of one or more activation pathways. The present findings
      demonstrate that the human mammary gland has the capacity to metabolically
      activate a dietary mutagen by several enzyme systems, including
      acetyltransferase, sulfotransferase, tRNA synthetase/kinase, and prostaglandin
      hydroperoxidase catalysis.

PMID- 9760589
TI  - Improvement of coronary artery disease in a patient with hyperhomocysteinemia:
      report of a case.

PMID- 9760590
TI  - Cytoprotective properties of melatonin: presumed association with oxidative
      damage and aging.
AB  - For years melatonin, a molecule widely produced in both the plant and animal
      kingdom, was thought to function exclusively as a synchronizer of seasonal
      reproduction, adjuster of the biological clock, sleep-inducing agent, and immune
      system stimulator. More recently melatonin has also been found to be a free
      radical scavenger and antioxidant. Although pharmacologic levels (higher than
      those normally present endogenously) of melatonin possess substantial protective
      activity against molecular damage inflicted by free radicals, its role as a
      physiologic antioxidant is currently under active investigation. Toxic free
      radicals have been implicated in a variety of age-associated degenerative
      diseases, as well as in aging itself. Because melatonin production falls
      substantially during aging, the loss of this antioxidant is theorized to be
      instrumental in the degenerative processes associated with advanced age. The
      exogenous administration of melatonin has been found to be effective in reducing
      macromolecular damage that is normally seen in experimental models of age-related
      disease. How effective melatonin will be in terms of deferring aging, however,
      must await the outcome on subsequent studies.

PMID- 9760591
TI  - Compatibility and stability of additives in parenteral nutrition admixtures.
AB  - The addition of additives (electrolytes, trace elements, and vitamins) to
      parenteral nutrition (PN) mixtures can lead to precipitation as a result of
      physical incompatibilities and can lead to chemical degradation of individual
      ingredients. The most significant cause of precipitation is excessive
      concentrations of calcium phosphate. The most significant cause of chemical
      instability is the oxidation of specific vitamins. The factors influencing
      calcium phosphate solubility include the commercial amino acid source, the
      calcium and phosphate salts used, temperature, magnesium concentration, and final
      volume. Precipitation can be avoided by organic phosphates. Trace element
      precipitation is most commonly caused by the formation of iron phosphate salts or
      copper cysteinate in cysteine-containing amino acid infusions. The least stable
      nutrient is ascorbic acid, which reacts with oxygen, and is catalyzed by copper
      ions. Oxygen originates from PN ingredients, the filling process, air remaining
      in the bag after filling, and oxygen permeation through the bag wall. Storage in
      multilayered bags with reduced gas permeability can protect residual ascorbic
      acid. Other chemical losses are caused by the reduction of thiamine by
      metabisulfite, and photodegradation of daylight-sensitive vitamins, especially
      retinol and riboflavin, during administration.

PMID- 9760592
TI  - Bioelectrical impedance analysis in nutritional research.

PMID- 9760593
TI  - Contribution by skeletal muscle to whole-body protein catabolism in critical
      illness: usefulness of urinary 3-methylhisitidine excretion.

PMID- 9760594
TI  - Food-derived carcinogens and breast cancer risk.

PMID- 9760595
TI  - Antioxidants and aging: is melatonin a possible, practical new hope?

PMID- 9760596
TI  - Dietary management of patients with hepatic encephalopathy in hospitals in the
      United Kingdom.

PMID- 9760597
TI  - Elimination of intraluminal colonization by antibiotic lock in silicone vascular
      catheters.

PMID- 9760598
TI  - Ceramides and ceramide metabolites in cell regulation: evidence for dietary
      sphingolipids as inhibitors of colon carcinogenesis.

PMID- 9760599
TI  - Lipid peroxidation of intravenous fat emulsions: a pharmaceutical issue with
      clinical impact?

PMID- 9760600
TI  - Diet and breast cancer.

PMID- 9760601
TI  - Is downsizing and disbanding specialty care teams a counterproductive strategy
      for cost reduction in health care?

PMID- 9760602
TI  - Dietary supplements.

PMID- 9760603
TI  - Evaluation of outcomes for patients with AIDS receiving home total parenteral
      nutrition.
AB  - This study evaluated the outcomes of patients with acquired immunodeficiency
      syndrome (AIDS) provided home total parenteral nutrition (HTPN) when specific
      criteria were used to initiate HTPN. Fifteen males who received HTPN and seven
      males who consumed only an oral diet were studied. The HTPN patients received an
      average of 55 kcal.kg-1.d-1 and 2.0 g of protein.kg-1.d-1 from HTPN and oral
      diet. Non-HTPN patients consumed an average of 35 kcal.kg-1.d-1 and 1.2 g
      protein.kg-1.d-1. Body weight (BW), lean body mass (LBM), and serum albumin (SA)
      were measured when HTPN was initiated or initial nutrition counseling was
      provided to the non-HTPN patients and again at the end of the study period. Over
      the study period, the HTPN patients gained an average 5.5 kg of BW and 3.0 kg of
      LBM, whereas the non-HTPN lost an average of 5.0 kg of BW and 3.0 kg of LBM. BW
      and LBM may be used to assess the response to HTPN in AIDS patients.

PMID- 9760604
TI  - Gastrostomy without laparotomy: a percutaneous endoscopic technique. 1980.

PMID- 9760605
TI  - Combined phacoemulsification and trabeculectomy versus trabeculectomy alone: a
      comparison study using mitomycin-C.
AB  - BACKGROUND AND OBJECTIVE: To compare the results of combined phacoemulsification
      and trabeculectomy (PEM/TRAB) plus mitomycin-C with those of trabeculectomy alone
      (TRAB) plus mitomycin-C. PATIENTS AND METHODS: The authors retrospectively
      reviewed 42 eyes in 38 consecutive patients who underwent combined PEM/TRAB with
      mitomycin-C. An age-matched control group of 42 patients who underwent TRAB with
      mitomycin-C during the same time period was randomly selected from 248
      consecutive patients. All patients had a minimum of 12 months of follow-up.
      RESULTS: Mean preoperative intraocular pressure (IOP) and number of glaucoma
      medications were similar for the two groups (22.8 +/- 6.9 mm Hg vs 22.9 +/- 6.8
      mm Hg, 2.12 +/- 0.8 vs 2.26 +/- 1.0 medications, combined PEM/TRAB vs TRAB,
      respectively). Postoperative IOP was significantly lower at all follow-up
      intervals. At final follow-up after a mean of 21.8 +/- 6.0 months, IOP averaged
      13.9 +/- 5.1 mm Hg in the PEM/TRAB group and 12.3 +/- 4.7 mm Hg in the TRAB
      group. Bleb survival was excellent in both groups, although slightly higher in
      the TRAB group (37 of 42 PEM/TRAB vs 41 of 42 TRAB). Both groups required
      significantly fewer glaucoma medications at final follow-up (0.38 +/- 0.6 vs 0.5
      +/- 0.8, PEM/TRAB vs TRAB). Complications were similar between the two groups.
      CONCLUSION: The success rate for combined PEM/TRAB appears to approach that of
      TRAB alone.

PMID- 9760606
TI  - Episcleral versus combined episcleral and intrascleral application of mitomycin-C
      in trabeculectomy.
AB  - BACKGROUND AND OBJECTIVE: To determine whether intrascleral exposure to mitomycin
      C (MMC) improves the control of intraocular pressure (IOP), increases the
      incidence of complications, or both. PATIENTS AND METHODS: The authors
      retrospectively evaluated 38 eyes of 29 patients following the intraoperative
      application of MMC (0.2 mg/ml; 5 minutes). In 21 eyes the MMC-soaked sponge was
      applied to the intact episclera (episcleral group). In 17 eyes, two sponges, one
      episcleral and the other intrascleral (sandwich group), were applied. The median
      follow-up times were 19.0 (episcleral group) and 24.0 (sandwich group) months.
      Outcome measures were the IOP, the number of medications, success rates, and the
      incidence of complications. RESULTS: The only statistically significant
      difference between the two groups was the 2-week postoperative IOP, which was
      significantly lower in the episcleral group (P = .0314). CONCLUSION: Because
      there is no additional benefit, the authors recommend that the intrascleral
      application of MMC be avoided. However, they did not observe increased
      complication rates when MMC was applied in this way.

PMID- 9760607
TI  - Transscleral cyclophotocoagulation with the diode laser for neovascular glaucoma.
AB  - BACKGROUND AND OBJECTIVE: To compare the outcome of transscleral
      cyclophotocoagulation (TSCPC) using a diode laser with that of TSCPC using an
      Nd:YAG laser in neovascular glaucoma. PATIENTS AND METHODS: The surgical outcome
      of diode laser TSCPC was retrospectively compared with that of free-running mode
      Nd:YAG laser (FR-YAG) TSCPC and continuous-wave mode Nd:YAG laser (CW-YAG) TSCPC.
      Twenty-one eyes of 21 patients in the diode laser group, 9 eyes of 9 patients in
      the FR-YAG group, and 9 eyes of 9 patients in the CW-YAG group were treated.
      RESULTS: The Kaplan-Meier life-table analysis revealed that the probability (mean
      +/- standard error) of successful intraocular pressure control with diode laser
      TSCPC at 3 years postoperatively was 47.2 +/- 12.6% per operation and 55.9 +/-
      16.3% per eye. Compared with the CW-YAG TSCPC, the diode laser TSCPC had a
      significantly higher probability of success throughout the follow-up period.
      Diode laser TSCPC was associated with improvements or preservation of visual
      acuity in 16 of 21 eyes (76%), and was the best of the three laser sources.
      Postoperative complications were minor following diode laser TSCPC. CONCLUSION:
      Diode laser TSCPC appears to be as effective as FR-YAG TSCPC and better than CW
      YAG TSCPC for treating neovascular glaucoma.

PMID- 9760608
TI  - A trial of dorzolamide for glaucoma.
AB  - BACKGROUND AND OBJECTIVE: To determine whether the effectiveness of dorzolamide
      changes when the drug is used under routine clinical conditions versus the more
      ideal conditions of a clinical trial. PATIENTS AND METHODS: A total of 118 eyes
      of 65 patients were assessed. Nine patients (15 eyes) received dorzolamide only,
      41 patients (74 eyes) received dorzolamide as an "add-on" medication, and 15
      patients (29 eyes) received dorzolamide as a substitute for an oral carbonic
      anhydrase inhibitor. RESULTS: At 1 month the intraocular pressure (IOP) had
      decreased from 23.5 to 19.9 mm Hg in the patients receiving dorzolamide only,
      from 18.6 to 16.4 mm Hg in the patients receiving dorzolamide as an add-on
      medication, and from 17.7 to 16.0 mm Hg in the patients receiving dorzolamide as
      a substitute for an oral carbonic anhydrase inhibitor. Similar decreases in IOP
      were present at 3 and 6 months. Local drug reactions occurred in 3 patients. Five
      patients stopped treatment because of severe symptoms of nausea and prostration.
      CONCLUSION: Under routine clinical conditions, dorzolamide was effective as a
      sole medication and as an add-on medication. It was at least as effective as oral
      acetazolamide. Local drug reactions sometimes occurred, as did systemic
      reactions.

PMID- 9760609
TI  - Corneal refractive and endothelial changes following THC:YAG (holmium) laser
      sclerostomy.
AB  - BACKGROUND AND OBJECTIVE: To determine the effect of THC:YAG (holmium) laser
      sclerostomy on corneal curvature and endothelial cell counts. PATIENTS AND
      METHODS: One hundred twenty-five cases were reviewed for high postoperative
      corneal astigmatism (> 5 D) or preoperative and postoperative endothelial cell
      count measurements in eyes without preoperative evidence of corneal endothelial
      compromise. RESULTS: Nine patients had keratometry reading at 2 to 3 months with
      documented corneal astigmatic changes of 5.62 to 12 D (mean 7.27 +/- 2.16 D).
      Sixteen eyes of 14 patients studied with specular microscopy had central mean
      endothelial cell count reductions of 6.5% following THC:YAG laser sclerostomy.
      The total energy applied correlated with the percentage reduction in endothelial
      cell counts (r = .507, P = .045, n = 16, Spearman correlation). CONCLUSION:
      Higher laser energy levels can result in high corneal astigmatism, which in some
      cases may be persistent, and a reduction in endothelial cell count.

PMID- 9760610
TI  - Ellipsoidal fitting of corneal topography data after arcuate keratotomies with
      compression sutures.
AB  - BACKGROUND AND OBJECTIVE: After paired arcuate keratotomies and compression
      sutures (AK) for treatment of high postkeratoplasty astigmatism, corneal
      topography tends to be irregular. The purpose of this study was to demonstrate a
      mathematical method for approximation of discrete corneal topography power data
      with an ellipsoid for better appreciation of the clinical outcome after AK.
      PATIENTS AND METHODS: Thirty-one eyes of 28 consecutive patient who underwent AK
      for excessive postkeratoplasty astigmatism were studied. Regular keratometry,
      corneal topography (TMS-1), subjective refraction, and best-corrected visual
      acuity (VA) were assessed preoperatively and at 1 week and 1 year
      postoperatively. A simplex algorithm was applied for fitting an ellipsoidal
      surface to raw corneal topography power data. A set of parameters (meridional
      power, axis, and asphericity) were calculated. The cylinder of subjective
      refraction was correlated with the keratometric readings, the simulated
      keratometry (SimK) of the topography system, and the respective parameters of the
      model surface. RESULTS: Keratometric astigmatism and the cylinder of the model
      surface decreased from 8.1 +/- 3.2 and 7.9 +/- 2.9 D preoperatively to 4.5 +/-
      2.1 and 5.3 +/- 2.0 D after 1 year, respectively. The asphericity in both
      meridional cross sections changed from a prolate ellipse preoperatively to an
      ablate ellipse at the early postoperative follow-up stage. Regarding the cylinder
      axis, there was a significant correlation of the model surface with the
      refractive cylinder at all examinations (P < .05), whereas there was no
      significant correlation of the SimK axis and the refractive cylinder axis.
      CONCLUSION: The approximation of corneal topography power data with an
      ellipsoidal model surface renders reconstruction of clinically relevant corneal
      topography parameters, including corneal asphericity with a marked data
      compression. Even in markedly irregular corneal surfaces, such as after AK, the
      correlation of amount/axis of refractive cylinder with the model surface
      parameters is more accurate than it is with respective SimK values of corneal
      topography analysis.

PMID- 9760611
TI  - Capsule-bending ring for the prevention of capsular opacification: a preliminary
      report.
AB  - BACKGROUND AND OBJECTIVE: To report the preliminary results of a study on the
      preventive effect of the capsule-bending ring on anterior and posterior capsule
      opacification (ACO and PCO, respectively). PATIENTS AND METHODS: The ring is an
      open, band-shaped, circular polymethylmethacrylate (PMMA) ring measuring 11 mm in
      diameter with pre-tension (13 mm in diameter when the ring is open), 0.2 mm in
      thickness, and 0.7 mm in width. To retain sharp edges, the ring is not polished.
      The sharp edges should create a sharp, discontinuous capsular bend in the fornix,
      which induces contact inhibition of migrating lens epithelial cells after
      cataract surgery. This capsule-bending ring is inserted into the capsular fornix
      following phacoemulsification, prior to the implantation of an intraocular lens
      (IOL). In a multicenter trial, 100 patients were scheduled to undergo
      phacoemulsification and IOL implantation in both eyes within 1 month. The
      procedure was performed with the ring in 1 eye and without the ring in the other
      eye of each patient. RESULTS: The anterior capsule was prevented from coming into
      contact with the IOL, and ACO was significantly reduced in the eyes with the
      ring, rendering the capsular opening larger 3 months after surgery. PCO was
      obviously reduced on slit-lamp examination in the follow-up period up to 6
      months, but needs to be evaluated during a longer period. CONCLUSION: This band
      shaped, sharp-edged capsule-bending ring may be useful for cases that need good
      fundus visualization for photocoagulation or expected vitreoretinal surgery and
      for the prevention of PCO.

PMID- 9760612
TI  - Digital palpation of intraocular pressure.
AB  - BACKGROUND AND OBJECTIVE: Previous studies investigating the accuracy of digital
      palpation through the eyelids to estimate intraocular pressure (IOP) have shown
      disappointing results. In this study, the accuracy of digital assessment of IOP
      by palpation of the bare cornea is investigated. MATERIALS AND METHODS: The IOP
      of a cadaveric eye model was varied from 5 to 40 mm Hg in increments of 5 mm Hg.
      Two examiners, one experienced and one inexperienced, digitally palpated the
      corneas and estimated IOP. The results were compared before and after a 1-hour
      training session. RESULTS: Prior to the training session, the experienced
      examiner guessed correctly 46% of the time and was correct within 5 mm Hg 100% of
      the time. The inexperienced examiner guessed correctly 21% of the time and was
      within 5 mm Hg 62% of the time. After the training session, the experienced
      examiner's score did not significantly (38% correct, 88% within 5 mm Hg, P = .05.
      CONCLUSIONS: Digital assessment of IOP by palpation of bare cornea is accurate
      when performed by experienced individuals. A minimal amount of training using the
      eye model may improve one's accuracy.

PMID- 9760613
TI  - Histologic effect of diode laser sclerostomy in human cadaver eyes.
AB  - BACKGROUND AND OBJECTIVES: To study tissue effects and thresholds of efficacy in
      producing a full-thickness scleral fistula in human eyes obtained from cadavers.
      The effect of laser sclerostomies created with indocyanine green (ICG) was also
      evaluated. MATERIALS AND METHODS: Ab externo laser sclerostomies were produced in
      12 fresh human eyes obtained from cadavers using a 200-micron diameter fiber
      optic connected to a diode laser system. Power settings were 500, 750, 1000,
      1250, 1500, and 2000 mW with a constant duration of 100 and 200 ms. The same
      diode laser settings were repeated in the tissues injected with ICG. RESULTS: The
      laser sclerostomies were associated with heat coagulation damage adjacent to the
      burn margins, with disruption of stromal collagen. Tissue damage was greater at
      higher power and longer duration. Scleral injection of ICG prior to laser
      sclerostomy did not enhance laser penetration. CONCLUSION: The diode laser can
      create a sclerostomy in human sclera with an optimum level of 1500 mW and 100 ms.
      ICG did not significantly enhance the ease of penetration or reduce the
      association thermal damage to the sclera.

PMID- 9760614
TI  - Treatment of total hyphema with relatively low-dose tissue plasminogen activator.
AB  - The purpose of this study is to investigate the efficacy of tissue plasminogen
      activator (tPA) in the treatment of total hyphema following ocular trauma or
      intraocular surgery. Three patients (3 eyes) representing unresolved total
      hyphema for more than 5 days and uncontrolled high intraocular pressure received
      intracameral injections of 10 microgram of recombinant tPA. Intracameral tPA
      injection resulted in complete resolution of hyphema in all 3 eyes. Resolution
      occurred mostly within 24 to 48 hours after injection. Possible side effects of
      tPA injection, such as increased intraocular pressure and corneal edema, were not
      observed. However, 1 eye had vitreous hemorrhage after repeated injections of
      tPA. Intracameral injection of tPA seems to be a safe and effective method for
      the treatment of unresolved total hyphema. However, repeated intracameral tPA
      injections may cause unwanted complications such as vitreous hemorrhage.

PMID- 9760615
TI  - Corneal marginal ulcer in relapsing polychondritis: treatment with
      keratoepithelioplasty.
AB  - This article describes a case of corneal marginal ulcer caused by relapsing
      polychondritis (RPC) that was treated with keratoepithelioplasty. The patient
      underwent keratoepithelioplasty with lamellar keratoplasty in the left eye. No
      relapse occurred in the nasal side in which corneal lenticules were grafted,
      whereas vascular invasion developed in the temporal side in which no lenticules
      were grafted. Keratoepithelioplasty was an effective surgical procedure to
      prevent a recurrence of corneal marginal ulcer in a patient with RPC.

PMID- 9760616
TI  - A pre-swedged silicone tube to simplify pigtail canaliculoplasty.
AB  - Silicone intubation of the canalicular system is indicated for stenting following
      canalicular trauma or surgery, or to dilate chronic stenosis of the punctum or
      canaliculus. Monocanalicular systems are available, but bicanalicular intubation
      is generally more stable and is particularly suitable for disease involving both
      the upper and the lower punctae or canaliculae. Bicanalicular intubation can be
      accomplished by intubating the entire lacrimal outflow system into the nose, or
      more simply by intubating the canalicular system alone using a pigtail probe. To
      use the pigtail probe to pass and fixate a segment of silicone tubing, the
      silicone tube is passed using a monofilament suture. A pre-swedged silicone tube
      segment on a monofilament suture has been designed to simplify the process of
      pigtail probe intubation of the canalicular system.

PMID- 9760617
TI  - Monomanual pupil stretcher.
AB  - The monomanual pupil stretcher is a new instrument that allows the authors to
      easily, quickly, and safely stretch the pupil. The specific features of the hooks
      allow pupil stretching to be performed in a single maneuver and in a more
      effective manner.

PMID- 9760618
TI  - Hook and loop fastener on loose prisms assists in measuring ocular deviation.
AB  - It is difficult to hold a pair of loose prisms in one hand. Doing so can lead to
      inaccuracy, which worsens with large-angle exotropia or vertical deviations. The
      authors applied a self-adhesive hooked Velcro (Velcro Sticky Back Tape, Velcro
      USA Inc., Manchester, NH) strip to the base and the top of loose prisms. They
      applied the complementary looped Velcro to a wooden bar. As a result, a pair of
      prisms could be suspended horizontally and/or vertically while being held in one
      hand. Forty consecutive patients undergoing strabismus surgery without adjustable
      sutures were retrospectively studied to evaluate the accuracy of this method.
      Clinical use confirmed its ease and convenience. Of 19 patients with exotropia
      and 15 patients with esotropia (mean ages 41.9 and 15.7 years, respectively; mean
      deviations 44.7 and 49.8 D, respectively), 4 patients with abducens paralysis,
      and 2 patients with trochlear palsies, 1 surgery achieved less than 10 D of
      residual deviation in all but 2 (5.9%). This simple, inexpensive system can
      assist with the clinical evaluation of ocular deviation.

PMID- 9760619
TI  - Conjunctival necrosis following the administration of subconjunctival
      corticosteroid.

PMID- 9760620
TI  - Influence of prosodic boundaries on comprehension of spoken English sentences.
AB  - Three experiments investigated the role of prosody in the comprehension of
      auditory sentences. In Exp. 1 an analysis of three novice talkers and one expert
      talker verified the production parameters of one type of syntactic ambiguity and
      showed that pitch cues were more prominent than duration cues. In Exp. 2, 16
      listeners used prosodic information to make consistent decisions reliably about
      phrase boundaries. In Exp. 3, 40 participants listened to sentences in which
      prosody was inconsistent with later morphosyntactic information, indicated their
      understanding, and then judged whether a visual target was related to the meaning
      of the sentence. Inconsistent prosody slowed comprehension and contributed to
      slower, less accurate judgments of sentence meaning. This suggests that prosodic
      information contributes to the perception of spoken language and can affect
      comprehension even when the syntactic structure indicated by prosody is
      contradicted by subsequent morphosyntactic information.

PMID- 9760621
TI  - Spatial ability in children's play with Lego blocks.
AB  - Sex differences in spatial ability have been argued to originate from sex
      differences in children's play preferences. Child (30 boys and 20 girls) were
      asked to construct a specific three-dimensional model using Lego blocks and were
      also given the Shepard and Metzler test of mental rotation. Those who completed
      the Lego model scored significantly higher in spatial ability than those who did
      not. Constructional ability was also related to errors made during the
      construction of the model, but spatial ability was the best predictor of
      completion of the model.

PMID- 9760622
TI  - An examination of Shneidman's application of Henry Murray's classification of
      needs to suicidal individuals.
AB  - 30 suicidal deaths were examined for the presence of needs described by Henry
      Murray. The most common needs identified were harmavoidance and infavoidance.
      Other needs were present rarely and typically only in unusual suicides such as
      double suicides or seppuku.

PMID- 9760623
TI  - Verbal contextual generalization in children with and without learning
      disabilities.
AB  - Braine's (1963) model of language development emphasizes the use of auditory or
      temporal processing so verbal contextual generalization can be produced. Recent
      literature on auditory or temporal processing skills of children with learning
      disabilities led to the prediction that these children would find it much more
      difficult to generalize contextually than would children without learning
      disabilities. The present study did not support this prediction. The implications
      were discussed in view of research on auditory or temporal processing skills of
      children with learning disabilities.

PMID- 9760624
TI  - The sex ratio, suicide, and homicide in nations of the world.
AB  - In a sample of 70 nations in 1980, those nations with higher proportion of males
      relative to females were less developed.

PMID- 9760625
TI  - Difficulty of a spatial task and sex difference in gains from practice.
AB  - The influence of practice on a difficult spatial task in a small sample of 11 men
      and 16 women was investigated. Participants were tested on a rotated embedded
      figures task modified from the Gottschaldt Hidden Figure Test prior to being
      given practice in identifying rotated and nonrotated embedded figures. One week
      after the pretest and practice session, the posttest was given. In the small
      sample studied, the number of correctly identified rotated figures on the
      posttest was significantly increased relative to pretest scores for men and
      women. However, the tendency for women to score higher than men after practice
      was not significant.

PMID- 9760626
TI  - SPECT (HMPAO) support for activation of the medial prefrontal cortices during toe
      graphaesthesia.
AB  - This experiment was designed to test the construct validity of psychometric
      analyses that suggested a strong functional association between the accuracy for
      toe graphaesthesia and selective activation of neurons within the medial
      prefrontal regions. Single Photon Emission Computerized Tomography (SPECT)
      profiles were obtained for three volunteers (2 men, 1 woman) after they had been
      exposed to a toe graphaesthesia task or had been exposed to the control setting.
      The two measurements for each participant were separated by at least one week.
      Qualitative evaluation, using criteria employed for clinical diagnoses, of serial
      coronal, sagittal, and horizontal sections clearly indicated a specific increase
      in uptake of tracer within the rostral one-third to one-half of the medial
      prefrontal cortices of all three subjects during the toe graphaesthesia task
      compared to that during baseline conditions. The results are consistent with our
      neuropsychological research which indicates that toe graphaesthesia may be an
      accurate and useful indicator of the functional integrity of the medial surfaces
      of the anterior cerebral hemispheres.

PMID- 9760627
TI  - Speech-Sounds Perception Test: analysis of a randomized answer form.
AB  - Responses to two forms of the answer sheet for the Speech-Sounds Perception Test,
      the standard form and a revised form in which the error types were randomized,
      were analyzed for 40 subjects. Although there was a statistically significant
      difference between the forms, practically it was negligible.

PMID- 9760628
TI  - Locomotion improves children's spatial search: a meta-analytic review.
AB  - This meta-analysis quantitatively summarized the developmental influence and the
      effects of locomotor experience as well as the benefits of locomotor practice,
      locomotor assistance, and active searching patterns on children's search
      performance. Based on specific criteria, a search of a database and reference
      lists identified 19 studies, including 1,029 children (510 boys and 519 girls)
      from 4 to 144 months of age. Outcome measures of spatial performance were
      converted to 83 effect sizes that reflected the effects of specific experimental
      characteristics. Analyses of variance indicated that with older children,
      locomotor activities are more important to their spatial searching. Locomotor
      status, searching patterns, locomotor assistance, test conditions, and test
      reliability were identified as moderator variables. In addition, locomotor
      training significantly improved children's spatial search. The results supported
      the hypothesis that children's development of spatial search skills is influenced
      by locomotor experience.

PMID- 9760629
TI  - Do monkeys choose the more skillful hand in manual problem-solving?
AB  - To investigate the relationship between manual skills and hand preference in 4
      female Japanese monkeys (Macaca fuscata), the technique of concurrent
      investigation of manual skills and hand preference was introduced. 4 female
      Japanese monkeys were required to take food out of a pipe using the left hand and
      right hand alternately. The performance time and the number of deviations from
      alternate sequence were recorded as measure of manual skills and hand preference.
      In the result, the preferred hand was not always consistently the skillful one;
      however, only one subject tended to choose the more skillful hand in problem
      solving, and another subject learned the alternate sequence of reaching. The
      performances of two subjects indicated discrimination of both hands in Japanese
      monkeys is possible.

PMID- 9760630
TI  - Suicide in eminent persons.
AB  - A review of several listings of famous historical figures indicated that
      percentages of deaths due to suicide ranged from 0.3% to 13.3%, with a median of
      2.9%.

PMID- 9760631
TI  - Assessment of abilities in basketball: a preliminary study.
AB  - Understanding the responding at two competitive levels of sports is prerequisite
      for successful identification and selection of the best athletes. The present
      study is a preliminary report about scores on 17 cognitive, perceptual, motor,
      and psychological measures of 13 elite Greek basketball athletes (national team),
      20 to 22 years of age, and 15 children on a national basketball team and 14 to 15
      years of age. Longitudinal studies must be conducted for the identification of
      the relationships among these measures and basketball performance and the
      development of a model for selection of athletes.

PMID- 9760632
TI  - Visuoperceptual speed of karate practitioners at three levels of skill.
AB  - The Identical Pictures Test was administered to 50 male and 45 female volunteer
      karateka who were classified by Fitts' level of learning and karate belt-rank
      color system (kyu-dan) into three groups. A 2 (sex) x 3 (skill) analysis of
      variance gave a significant difference for skill and sex. Over-all, the
      practitioners in the autonomous stage (black belts) and the women had faster
      visuoperceptual speed.

PMID- 9760633
TI  - Dissociation between specific personal episodes and other aspects of remote
      memory in a patient with hippocampal amnesia.
AB  - In this paper, we describe some features of remote memory in a single-case, Y.K.,
      with amnesic syndrome. His ability to access remote memory was investigated
      through a variety of tests and then analyzed in terms of specific aspects of
      remote memory, i.e., public events, personal semantic memory, and specific
      personal episodes. Although Y.K. showed relatively good performance in recalling
      public events, personal semantic memory, and general personal events, he was not
      able to recall specific personal episodes over his entire life span. That is,
      there appears a clear dissociation between recalling specific personal episodes
      and other aspects of remote memory. This suggests he lacks "richness" in his
      remote memory, which is probably necessary to maintain one's own identity.

PMID- 9760634
TI  - Body perceptions of bulimic and nonbulimic groups.
AB  - A brief survey measuring satisfaction with the body, concern for physical
      appearance, and motivations for selection of clothing was administered to 30
      women in a university-sponsored support group for bulimic students and 30 women
      randomly selected from a college campus. No mean differences were found between
      the groups on concern for physical appearance when in a social setting, but mean
      differences were significant on satisfaction with weight, satisfaction with body
      image, and concern for physical appearance when alone.

PMID- 9760635
TI  - Reliability of two measures of health-related quality of life in patients with
      multiple sclerosis.
AB  - Multiple sclerosis is a chronic neurological disease which can cause a variety of
      symptoms (motor and sensory impairment, visual problems, bladder and bowel
      problems, sexual dysfunction, and decline in cognitive function). Both the
      Medical Outcome Study Short Form-36, a generic questionnaire regarding health
      related quality of life, and the Disability and Impact Profile, a similar
      questionnaire developed for people with chronic diseases, are used regularly to
      assess patients with multiple sclerosis. Over a 6-mo. interval 187 patients with
      multiple sclerosis completed these questionnaires twice. Internal consistency of
      both questionnaires at Times 1 and 2 was .60 or above for all eight scales of the
      Medical Outcome Study Short Form-36 and five scales of the Disability and Impact
      Profile. Estimates of test-retest reliability for three scales of the Medical
      Outcome Study Short Form-36 were below .60, but for all scales of the Disability
      and Impact Profile were .60 or higher. The two questionnaires appeared to be
      reliable for our sample of patients with multiple sclerosis.

PMID- 9760636
TI  - Life satisfaction, suicide, and homicide.
AB  - In 1985 in 18 nations measures of life satisfaction in college students were not
      associated with the suicide and homicide rates of 15- to 24-yr.-olds.

PMID- 9760637
TI  - Men and women holding hands: whose hand is uppermost?
AB  - This study explored the issue of whether status and power differences are
      expressed in the way men and women hold hands. It was hypothesized that men's
      hands would be upper in heterosexual handholding couples significantly more often
      than women's. Also, to explore the possibility that height differences of
      handholding partners might affect handholding position, all handholding couples
      observed in this study were classified as couples with men and women of equal
      height or couples where either the men or women were taller. A total of 1,006
      handholing couples were observed, and men's hands were significantly more likely
      to be the upper one in couples when men were taller than women and in couples
      where men and women were of equal height, suggesting that, while height does
      matter, it is less important for this handholding pattern than sex differences.

PMID- 9760638
TI  - Reinterpreting telepathy as unusual experiences of empathy and charisma.
AB  - Telepathy is often dismissed because it is judged to be contrary to the accepted
      facts of social psychology. This article argues that what is called telepathy may
      require nothing more than empathy and charisma and is reducible to these
      sociopsychological constructs. Two studies explore this hypothesis. In the first
      the proposed relationship is used to explain the sheep-goat effect. In the second
      study scores on charisma and empathy are used as direct predictors of telepathy
      scores. The results in combination support the interpretation of telepathy as
      phenomenologically impressive social psychological events which in less dramatic
      instances are termed empathy and charisma.

PMID- 9760639
TI  - Effect of different quantities of variable practice on acquisition, retention,
      and transfer of an applied motor skill.
AB  - This investigation examined the effect of manipulating different quantities of
      variable practice in the acquisition phase on the retention and transfer
      performance of a dart throw. Participants in the Specific condition practiced a
      total of 75 acquisition trials from a distance of 2.39 m. Participants in the
      Specific + Variable condition practiced a total of 75 acquisition trials with 25
      trials from distances of 1.47 m, 2.39 m, and 3.30 m. Participants in the Specific
      + Varplus condition practiced a total of 75 acquisition trials with 15 trials
      from distances of 1.47 m, 1.93 m, 2.39 m, 2.84 m, and 3.30 m. Results of the one
      way analysis of variance on the 24-hr. retention test from 2.39 m yielded no
      significant differences among practice conditions for mean radial error. A one
      way analysis of variance on the 24-hr. transfer test from 3.76 m indicated that
      the Specific + Variable and Specific + Varplus conditions performed with
      significantly smaller mean radial error than the Specific condition. The results
      are discussed in regard to recent research and applicability to instructional
      settings.

PMID- 9760640
TI  - Effect of warning on feigned malingering on the WAIS-R in college samples.
AB  - Research indicates claimant malingering of cognitive deficits to be common in
      personal injury litigation. Efforts have been made to either detect such
      tendencies or deter efforts at malingering. The present study examined whether
      warning people that feigned malingering efforts would be detected results in more
      valid profiles on the Wechsler Adult Intelligence Scale-Revised. Undergraduates
      (N = 48) were randomly assigned to one of three conditions: feigned malingerers
      without warning, feigned malingerers with warning, and controls. Analysis
      indicated both feigned malingerer groups performed significantly worse than the
      control group; however, feigned malingerers with warning did not perform
      significantly better than those without warning. Unlike previous research using
      the Wechsler Memory Scale-Revised, results did not support effectiveness of
      warning in reducing feigned malingering scores.

PMID- 9760641
TI  - Self-concept of academic ability as a function of sex, age, and academic
      achievement among African adolescents.
AB  - This study examined (a) sex and age variations for scores on Self-concept of
      Academic Ability and academic achievement among 244 African adolescents attending
      a coeducational high school and (b) correlations between scores on Self-concept
      of Academic Ability and academic achievement by sex and age. No significant sex
      differences were found, but there were significant age differences on the Self
      concept scores and measures of English, science, and history but not in
      mathematics. A significant positive correlation was found between Self-concept
      scores and academic achievement for boys and girls and in all age groups, but the
      magnitude of the correlations with achievement in mathematics was stronger among
      boys than among girls.

PMID- 9760642
TI  - The use of long guns for murder.
AB  - In 1980, long guns were used relatively more often for murder in states which
      were more rural and which had a greater proportion of hunters.

PMID- 9760643
TI  - Time course analysis of the reverse-Stroop effect in Japanese Kanji.
AB  - A reverse of the Stroop effect was obtained with Japanese kanji (logographic
      script) but not with Japanese kana (syllabic scripts) by Morikawa in 1981. In the
      present study, the normal effect on reaction times by word and color was altered
      by presenting the words before or after the color. The reverse Stroop effect was
      observed with kanji but not with kana even when the color was presented prior to
      the word. It was shown that the difference between kanji and kana in the reverse
      Stroop effect could not be explained by the relative speed of processing of word
      and color and that the reading process of kanji is different from that of kana.

PMID- 9760644
TI  - Selective effects of physical exercise on choice reaction processes.
AB  - The aim of the present study was to examine the effects of an exercise of
      moderate intensity (60% of maximal aerobic power) on specific information
      processing mechanisms. 22 students completed 3 10-min. exercise bouts on a
      bicycle ergometer. Concomitantly, participants performed six manual-choice
      reaction tasks manipulating task variables (Signal Intensity, Stimulus-Response
      Compatibility, and Time Uncertainty) on two levels. Reaction tests, randomly
      ordered, were administered at rest and during exercise. A significant
      underadditive interaction between Time Uncertainty and exercise was found for the
      highest quartiles of the distribution of reaction times. No other interaction
      effects were obtained for the other variables. These results reasonably support
      that moderate aerobic exercise showed selective rather than general influences on
      information processing.

PMID- 9760645
TI  - Variation of suicide and homicide rates by longitude and latitude.
AB  - State suicide rates in 1980 varied gradually, rather than abruptly, with
      longitude, as did homicide rates with latitude.

PMID- 9760646
TI  - Some relationships between skills in word-category recall and factors in adults'
      aphasia.
AB  - It has long been recognized that a basic dimension to the lexical organization of
      the brain is semantic, and some brain mapping studies have indicated that the
      brain fields are distinctly different from some grammatical classes. Findings
      from the present investigation showed consistent relationships between 29 aphasic
      adults' performances on tasks involving graphic and gestural skills and those
      involving sequential recall of spoken words from different word categories. Each
      adult received the Porch Index of Communication Abilities which relies upon the
      physical manipulation of objects to assess verbal, gestural, and graphic
      abilities. Scores on a test requiring recall of word strings of nouns, verbs,
      adverbs, adjectives, or prepositions were used to predict the subscale scores
      from the Graphic and Gestural factors of the index. Recall scores for verb and
      preposition were predictive of the aphasic subjects' performances on the Graphic
      subscale, and noun and preposition scores were predictors of subjects' scores on
      the Gestural subscale. The results are related to other research showing that
      verb and preposition skills are predictive of fine motor abilities of children
      with communication disorders and brain-mapping studies. Some discussion centers
      on possible overlapping functions of brain activity involving word categories,
      language, and fine motor skills.

PMID- 9760647
TI  - Sleep in relation to age, sex, and chronotype in Japanese workers.
AB  - The Morningness-Eveningness Questionnaire and Life Habits Inventory were
      administered to 622 Japanese workers matched for sex and age. We investigated the
      distributions of the scores on the Morningness-Eveningness Questionnaire and
      sleep-wake habits by age and sex. Subjects were classified into five age groups
      and three chronotypes. The distributions and mean scores on the questionnaire
      advanced slightly toward the Morning type from the young to the aged group. The
      habitual bedtimes and waking times were significantly earlier in all the
      chronotypes from the young to the aged group, and the preferred bedtimes and
      waking times were also clearly earlier from the young to the aged group. The
      length of sleep was shorter for the Evening than the Morning types, especially in
      the group below 24 yr. The differences in habitual and preferred sleep length
      were greater than 1 hour for all age groups, especially the two groups under 34
      yr. The number of awakenings during night sleep increased from the young to the
      aged group for all chronotypes. The older Evening type tended more toward
      frequent napping and longer naptime. The variabilities of bedtime and sleep
      length were larger for the young and Evening type than for the old group and
      Morning types. Further, the mood upon waking and satisfaction with sleep length
      were better in the aged Evening type than the young Morning type. The women under
      44 yr. woke up earlier than the men of the same age, and the women of the 35-54
      yr. groups had a shorter length of sleep than others. These may be related to
      childcare and housework. These results indicated that the phase of circadian
      rhythms had moved forward from the young to the aged group, and the individual's
      rhythm, of those that were aged Morning types, showed better agreement with sleep
      wake rhythms than did others.

PMID- 9760648
TI  - Numbers of details in the reconstruction of an emotional narrative decrease
      linearly as a function of time.
AB  - 33 university students listened to a 5-min. ambiguous narrative about a young boy
      (The Billy Story) while another 33 students did not. At the end of the final
      examination for the course the students were promised a 2% bonus mark if they
      could reconstruct the details of the story. Whereas only one student who heard
      the story could not recall any details, 30% of the students (n = 9) who never
      heard the story generated a false one. The numbers of accurate details recalled
      by those who heard the story decreased linearly with the time (5 through 30
      days). Five times the numbers of the women than men who heard the story
      attributed the young boy's anomalous experience to sexual abuse.

PMID- 9760649
TI  - Stress triggers of long, short, and variable sleep patterns.
AB  - Sleep and stress patterns in 34 young adult sleepers were measured. Time series
      analysis of sleep report measured 6- and 3-day patterns of light stress preceding
      a change in sleep pattern for long (n = 15) and short or variable (n = 7 and 12)
      sleepers, respectively.

PMID- 9760650
TI  - Human classical conditioning of visual compound stimuli in paired-associate
      tasks.
AB  - College students in introductory psychology participated in four experiments to
      investigate the salience of color versus figure elements of paired associates.
      The study also reviewed the process of learning paired associates within the
      context of first-order simultaneous classical conditioning. In Exp. 1, four
      separate classes received different treatments concerning the position and type
      of stimulus element (color of figure) they were instructed to recall. There were
      seven trials with a 30-min. delay between the sixth and seventh trials. The
      results indicated that the groups who were required to remember the figure
      element of the pairs, significantly out-performed the color groups and also
      learned the pairs much faster. Also, there was a sharp rise in mean correct
      responses remembered after a 30-min. delay for the group required to recall the
      color element of the paired associates. Exp. 2 was a within-subjects comparison
      of the effectiveness of the color and figure elements as stimuli. Again, the
      figures elicited more correct responses than colors. Exp. 3 tested the
      effectiveness within subjects of the stimulus elements as response factors. As
      responses, however, there were no significant differences in the number of
      correct answers when recalling color or figure elements until the 30-min. delay
      between Trials 6 and 7. As expected in Exp. 4, figures elicited significantly
      more functional descriptions than did colors, suggesting that figures possess a
      logographic nature which acts as a mnemonic device aiding in the memory of
      stimuli and responses.

PMID- 9760651
TI  - Joseph Richman's signs for distinguishing genuine from simulated suicide notes.
AB  - Scores from two independent judges indicated that criteria derived from the
      clinical experience of a suicidologist were successful in differentiating genuine
      from simulated suicide notes.

PMID- 9760652
TI  - Order of item difficulty on the WAIS-R picture arrangement subtest: data from a
      traumatically brain-injured sample.
AB  - Although the items within the WAIS-R subtests are presumed to be in ascending
      order of difficulty, several studies have indicated that the Picture Arrangement
      subtest items are out of order for clinical groups. The present study
      retrospectively examined item difficulty and discrimination in the test data of
      74 individuals who had been referred for neuropsychological assessment following
      a traumatic brain injury. While results were not statistically significant,
      qualitative analysis of partial credit scoring for four of the items indicated
      some inconsistencies in the scoring rationale. Caution is recommended in the use
      and interpretation of the Picture Arrangement tests scores in the assessment of
      individuals with traumatic brain injury.

PMID- 9760653
TI  - Revising and validating the random search model for competitive search.
AB  - A random search model was fit to a total of 2592 visual search times on a single
      target detection task. By using a competing homogeneous background and uniform
      stimulus material, specifying viewing distance, controlling the presentation of
      search task material, and eliminating some options for extreme search strategies,
      very high correlation coefficients were found when a random search model was fit
      to both the individual data and to pooled data. A response time parameter was
      incorporated into the traditional random-search model and very good predictions
      of search performance were obtained.

PMID- 9760654
TI  - Clinical aspects associated with adjustment in unusual sleepers.
AB  - Sleep behavior and self-reported adjustment of 93 young adult sleepers were
      measured. The 34 unusual sleepers (short, long or variable) differed in
      adjustment from controls. 7 short sleepers reported more intense, worrisome
      responses than other unusual sleepers and controls.

PMID- 9760655
TI  - Word-type effects in word-stem priming: evidence for semantic processing in the
      perceptual representation system?
AB  - While a presemantic Perceptual Representation System is believed to mediate
      implicit memory tasks such as word-stem priming, clinical studies suggest
      semantic information can be processed during priming. To clarify the nature of
      this system, we investigated word-type effects in word-stem priming in a
      nonclinical sample of 41 undergraduates who rated the pleasantness of threatening
      and nonthreatening words, performed implicit and explicit memory tasks, and
      completed measures of mood state. More nonthreatening words were primed and
      scores on the Beck Depression Inventory were negatively correlated with
      production of nonthreatening words. During cued recall, more threatening than
      nonthreatening words were remembered and ratings of state anxiety were negatively
      correlated with recall of nonthreatening words. Our findings support the
      contention that semantic information is processed during priming and that mood
      congruent biases also operate. These results may call for a reconceptualization
      of the Perceptual Representation System.

PMID- 9760656
TI  - Correlations between two Multidimensional Anxiety Scales for Children.
AB  - The correlation between scores on two new anxiety questionnaires for children (ns
      = 54 boys, 54 girls), the Screen for Child Anxiety Related Emotional Disorders
      and the Multidimensional Anxiety Scale for Children was .72, with values for
      subtests ranging between .35 and .63.

PMID- 9760657
TI  - Vividness of visual and haptic imagery of movement.
AB  - This study investigated the relationships between visual and haptic imagery of
      movement. A total of 338 subjects, all university students aged between 18 and 26
      years, completed the Vividness of Movement Imagery Questionnaire, which evaluates
      capacity for visual imaging, and a modification of this questionnaire, the
      Vividness of Haptic Movement Imagery Questionnaire, designed to evaluate capacity
      for haptic imaging. Scores on the two questionnaires were significantly
      correlated .60.

PMID- 9760658
TI  - Color or brightness effects on grip strength?
AB  - Research into the effects of color on grip strength has produced inconsistent
      results, but studies show methodological problems, for example, the non
      standardised reporting of stimulus colours, differing intertrial rests, and the
      neglect of warm-up effects. The present study was designed to replicate the 1989
      work by Hasson, et al. and also to examine potential brightness effects of
      stimuli on grip strength. Analysis indicated brightness effects might confound
      potential to produce Type I errors.

PMID- 9760659
TI  - Defense Mechanism Test and electrodermal activity.
AB  - Electrodermal activity was registered during examination with the Defense
      Mechanism Test of 21 patients diagnosed with anxiety disorder, affective
      disorder, or schizophrenic disorder. The test can be interpreted as a model
      situation of how a person defends himself against a threat to avoid anxiety. We
      used Andersson's modified version of the test and tested the hypothesis that
      electrodermal activity should increase when there were responses categorised as
      Anxiety and decrease when there were responses categorised as defences or when
      the threat was correctly identified. We found significant increase in all
      electrodermal variables in connection with responses categorised as Anxiety.
      After exposures with responses categorised as Isolation, the maximal skin
      conductance level and the magnitude of late nonspecific responses were
      significantly decreased. After exposures when the threat was identified and thus
      no longer subliminal, the electrodermal activity was significantly decreased. All
      these findings support our hypothesis. After exposures with significantly
      decreased. All these findings support our hypothesis. After exposures with
      responses categorised as Denial all electrodermal variables were significantly
      increased. Similarly in responses categorised as Repression, Introaggression, and
      Disavowal or denial of hero's sex the frequency of late nonspecific responses
      were significantly increased. The increased electrodermal activity could be due
      to insufficient defence strategies as categorised in the Defense Mechanism Test.

PMID- 9760660
TI  - Attitude towards aggression and creative functioning in patients with breast
      cancer.
AB  - Three projective personality tests were used to assess attitude to aggression
      (The Identification Test), anxiety and defenses (The Meta-Contrast Technique) and
      creative functioning (The Creative Functioning Test) in 70 patients with breast
      cancer. Discriminant analyses were applied pro primo to characterize
      psychologically patients with a better prognosis and patients with a poorer
      prognosis. A second aim was to characterize psychologically older
      (postmenopausal) and younger (premenopausal) women. Generally, high scores on the
      Identification Test indicated maladaptive attitudes towards aggression among all
      the patients. Patients with a poorer prognosis showed responses that in healthy
      subjects indicate acknowledgement of aggressive impulses, perhaps suggesting lack
      of "defenses" against such impulses among those patients. Another way to describe
      it would be that patients with a better prognosis seem to have (normally
      nonadaptive) "defenses" against aggressive impulses while those with poorer
      prognosis have not. Surprisingly, the patients with a better prognosis (but not
      those with a poorer prognosis) gave responses classified as depression in the
      Meta-Contrast Technique. Typical of premenopausal patients were responses
      classified as anxiety as well as reaction formation on the Identification Test.
      Responses classified as adaptive defenses (isolation) were seen in the Meta
      Contrast Technique. A surprising finding was that many of these patients were
      characterized by high scores on the creativity test. These original statistically
      significant findings of attitudes towards aggression and creative functioning in
      breast cancer patients are discussed in relation to the underlying nature of
      aggression and creativity.

PMID- 9760661
TI  - Anticipatory cues can interfere with inhibitory operant behavior in the rat.
AB  - In four separate experiments a total of 24 male rats were trained for 30 min.
      daily in the same temporal order to inhibit their responses for at least 6 sec.
      before a response-contingent reward was delivered (DRL-6 sec.). The rats tested
      as the second group each day displayed about twice the number of errors (effect
      size = 40%) shown by rats tested in the first or third groups. These results
      suggest that anticipatory cues, acquired within two sessions, interfere with
      response inhibition during an appetitive task for a limited time (between a few
      minutes to about one hour). The results are consistent with the hypothesis that
      learned anticipation of reward may decrease inhibitory mechanisms by facilitating
      limbic lability.

PMID- 9760662
TI  - Preliminary study on the effect of rocking on activities of persons with severe
      mental and physical handicaps.
AB  - In this preliminary observation, a group of seven mentally and physically
      handicapped persons of chronological ages ranging from 15.4 yr. to 26.8 yr.
      experienced 15 sec. of physical rocking. For the further analysis, the
      poststimulus periods were classified into either those when the subjects'
      spontaneous head, mouth, and body movements had increased from the prestimulus
      period or those decreased. The median heart rates recorded in the poststimulus
      period were not significantly different from those in the prestimulus period on
      trials on which there was an observable increase in the rates of spontaneous
      head, mouth, and body movements; however, the median heart rates decreased during
      those trials on which a decrease in the rates of the movements occurred. Since it
      is said that rocking heightens arousal of persons with mental and physical
      handicaps, it is suggested that spontaneously emitted, aimless head, mouth, and
      body movements attributed to low arousal were reduced by heightened arousal
      rather than by a decline in participants' activities.

PMID- 9760663
TI  - Reply to Greenberg's critique of Malik, et al.'s experiment on the method of
      subliminal psychodynamic activation.
AB  - Greenberg raised two issues concerning an experiment reported by Malik, et al. on
      the method of subliminal psychodynamic activation. One relates to the
      appropriateness of control and threshold stimuli and the other to the use of
      subjective thresholds. Both concerns are addressed.

PMID- 9760664
TI  - Perceptions of the heart-rate guide.
AB  - Preliminary assessment was made concerning perceptions of the newly developed
      heart-rate guide, devised as an educational tool to promote physical activity.
      Unlike the traditional target heart-rate chart, the heart-rate guide illustrates
      the value of low to moderate intensity physical activity. Following a brief
      lecture about the Surgeon General's report on physical activity and health and
      the usefulness of heart-rate charts and guides, 120 college students (M age 21.5
      +/- 2.8 yr.) completed a self-report survey consisting of statements regarding
      their use of target heart rates during exercise and their perceptions of the new
      heart-rate guide as compared to the traditional heart-rate chart. 83% of the
      subjects reported that the new guide better illustrated the findings from the
      Surgeon General's report, 5% reported no difference between the guide and the
      chart, and 12% reported that the chart better illustrated the report's findings
      (p < .01). 48% never measure their heart rates when they exercise, 48% sometimes
      measure their heart rates and 4% always do so (p < .01). While the new guide
      should not replace the traditional chart, these results suggest that college
      students perceive the heart-rate guide as a useful tool despite the fact that
      only a small percentage of students regularly measure their heart rates when they
      exercise.

PMID- 9760665
TI  - Heights of U.S. Presidents: a trend analysis for 1948-1996.
AB  - A Mann Trend Test yielded a trend in increased height for 10 U.S. Presidents from
      1948-1996, consistent with previous findings that height is a heuristic for
      dominance.

PMID- 9760666
TI  - Short-term memory for faces: ageing and the serial position effect.
AB  - Properties of short-term memory for faces (Exp. 1) were investigated in 40 young
      and 30 elderly persons and compared with short-term memory for non-verbal shapes
      (Exp. 2) with 30 new persons in a young group and an elderly one. Young subjects
      displayed a U-shaped curve for both kinds of stimuli, and elderly subjects
      displayed a U-shaped curve, but the recency effect was abolished for faces (in
      one condition). This suggests a possible specific short-term store for faces.

PMID- 9760667
TI  - Spiral maze performance in dementia.
AB  - 58 patients with probable Alzheimer dementia and 58 with probable multi-infarct
      dementia were given spiral mazes of differing complexity and 20 other
      neuropsychological tests. When age and over-all neuropsychological functioning
      were taken into account, spiral maze performance was poorer for patients with
      multi-infarct dementia but there were no significant group differences related to
      task complexity or indices of performance strategy.

PMID- 9760668
TI  - Effects of melatonin in two individuals with Alzheimer's disease.
AB  - Dementia has been associated with circadian rhythm disturbances expressed in
      several dimensions including body temperature, hormonal concentrations, sleep and
      wakefulness patterns, and rest-activity cycles. These disturbances may be the
      result of a dampening in the amplitude of the circadian rhythm. One of the
      symptoms associated with the aging process has been a decline in the amplitude of
      the melatonin rhythm. Here, the results of melatonin administration to two
      patients with Alzheimer's disease are presented. Melatonin administration
      enhanced and stabilized the circadian rest-activity rhythm in one of the patients
      along with some reduction of daytime sleepiness and an improvement in mood. The
      other patient, who was characterized by less cognitive impairment, showed no
      significant changes associated with melatonin ingestion. Interestingly, the
      acrophase of rest-activity was delayed for about one hour in both patients. These
      results suggest that melatonin may have beneficial effects in some patients with
      Alzheimer's disease.

PMID- 9760669
TI  - Threshold effect in visual perception of geometrical figures.
AB  - Filtering of the input image has been shown to play a central role in several
      aspects of visual perception. In our experiments in visual perception of the area
      of geometrical figures the orientation in random dot patterns, and some visual
      illusions, we have shown that a threshold effect inferred from the filtering of
      the input image produces a perceptual error. This error has been explained by
      using the concept of Image Function. The present paper is a brief review of our
      experimental results and of the models we have proposed.

PMID- 9760670
TI  - Self-esteem and injury in competitive field hockey players.
AB  - A volunteer sample of 50 competitive field hockey players completed the
      Coopersmith Self-esteem Inventory at pre- and postseason and prospectively
      collected injury data over a 20-wk. season. Multiple regression analysis showed
      no relationship between scores on Self-esteem and the number of injuries, the
      participation time affected due to injury, and sex of players. Further multiple
      regression analysis showed that frequency of the more severe injuries
      significantly predicted scores on Self-esteem. This finding can be interpreted as
      evidence of the relationship between low self-esteem and injury in sport.

PMID- 9760672
TI  - Steven Stack's ecological studies of national suicide rates.
AB  - The results of eight studies by Steven Stack on national suicide rates were
      replicated using a data set for 1980; however, a multivariate data analysis
      indicated that the many associations found by Stack reduced to one major
      correlate of national suicide rates--females' participation in the labor force.

PMID- 9760671
TI  - Effects of three stimulus parameters on eye position in cerebral palsied adults.
AB  - Bilateral eye position was measured in 6 cerebral palsied adults to assess the
      effects of stimulus dimensions (horizontal, vertical), amplitude (+/- 4 degrees,
      +/- 6 degrees, +/- 8 degrees), and frequency (0.3, 0.5, 0.7 Hz) on saccadic and
      pursuit movements. The head-free, corneal reflection method was used for 54 10
      sec. trials of square, triangle, and sine wave stimuli. Shared variance between
      each eye's position and the stimulus was tested by Wilcoxon T (dimension) and
      Friedman analysis of variance (amplitude, frequency) showing that the effects of
      saccadic and pursuit dimension and amplitude were individualized with regard to
      subject and right and left eye positions. The bilateral eye position of 5 of 6
      subjects was affected by saccadic frequency; pursuit frequency affected bilateral
      eye position of 4 of 6 subjects. The lowest shared variance (critical difference
      in ranks) was at 0.7 Hz. The results are discussed with regard to subjects'
      disability, stimulus velocity, and frequency of directional reversal. Reversal
      may be the most critical stimulus property.

PMID- 9760673
TI  - Stroop interference is the result of comparable, not of differential processing
      speeds of two stimulus dimensions.
AB  - On a digit-counting Stroop task, processing of the slower, nonverbal, i.e.,
      number, dimension was slowed further by a large-number set (6 to 9), as compared
      with a small-number set (1 to 4). In the task, neutral symbols or conflicting
      digits were arranged on a horizontal line (e.g.,@@, 444) and on two separate
      sheets. Each sheet contained 120 stimulus arrays. Subjects counted out loud the
      number of symbols or digits in each array, and their counting times for each
      sheet were recorded. 23 subjects received the small-number set while 21 received
      the large-number set. It was found that counting a large number of symbols took
      significantly longer time (by 162 sec. per 120 stimulus arrays) than counting a
      small number of symbols. Moreover, interference was nonexistent (2 msec. per
      stimulus array) when a large number of conflicting digits were counted but was of
      a typical magnitude (110 msec. per stimulus array) when a small number of
      conflicting digits were counted. This suggests that Stroop interference is better
      explained as the result of comparable, not of differential, processing speeds of
      the two stimulus dimensions. Implications for the cause and the locus of Stroop
      interference are discussed.

PMID- 9760674
TI  - Renin inhibitors.

PMID- 9760675
TI  - The discovery and development of angiotensin II antagonists.

PMID- 9760676
TI  - Development of an orally active tripeptide arginal thrombin inhibitor.

PMID- 9760677
TI  - Discovery and development of an endothelin A receptor-selective antagonist PD
      156707.
AB  - PD 156707 is a highly potent, selective antagonist of the ETA receptor that has
      demonstrated efficacy in a number of different disease models. The next few years
      will be exciting in the field of ET research as several compounds progress
      through clinical development. It is our hope that the efficacy that data
      demonstrated to date with PD 156707 will some day be translated into real hope
      for the patients who are waiting beyond the confines of our research
      laboratories.

PMID- 9760678
TI  - Endothelin receptor antagonists.

PMID- 9760679
TI  - LHRH antagonists.
AB  - After almost two decades, the research on LHRH antagonists has produced a number
      of decapeptides that are currently in clinical studies. The structures of these
      antagonists, unlike the agonists, differ substantially from that of LHRH. Five of
      the ten amino acids are unnatural and of D configuration. The structural
      combination of a hydrophobic N-terminus (residues 1, 2, and 3) and a
      basic/hydrophilic C-terminus (residues 6 and 8) was thought to be responsible for
      some HR reactions encountered with the second generation of LHRH antagonists.
      This side effect was greatly reduced by substituting the appropriate combination
      of amino acids at positions 5, 6, and 8. The next hurdle in the drug development
      of LHRH antagonists was solubility and aggregation. In the case of A-75998, water
      solubility was improved by 12- to 25-fold via substitution of NMeTyr at position
      5. However, based on DLS analysis, the aqueous solutions still contained some
      large aggregates that were not visible to the naked eye. This formation of
      aggregates was eliminated on formulating A-75998 in Encapsin. In men, a single
      s.c. dose of 2 mg of A-75998 suppressed T to the castrate levels for over 30 hr.
      Other LHRH antagonists including ganirelix and cetrorelix are also in phase I/II
      clinical studies. Clinical studies with cetrorelix in prostate cancer; in vitro
      fertilization, and benign prostate hypotrophy have been reported.

PMID- 9760680
TI  - LHRH agonists.

PMID- 9760681
TI  - Discovery and development of somatostatin agonists.

PMID- 9760682
TI  - Factors impacting the delivery of therapeutic levels of pyrone-based HIV protease
      inhibitors.

PMID- 9760683
TI  - The integration of medicinal chemistry, drug metabolism, and pharmaceutical
      research and development in drug discovery and development. The story of
      Crixivan, an HIV protease inhibitor.

PMID- 9760684
TI  - De novo design and discovery of cyclic HIV protease inhibitors capable of
      displacing the active-site structural water molecule.

PMID- 9760685
TI  - Discovery and development of the BHAP nonnucleoside reverse transcriptase
      inhibitor delavirdine mesylate.

PMID- 9760686
TI  - Famciclovir. Discovery and development of a novel antiherpesvirus agent.

PMID- 9760687
TI  - The use of esters as prodrugs for oral delivery of beta-lactam antibiotics.
AB  - It is apparent that the sequence of events that has been followed in the approach
      to the discovery and development of a new beta-lactam prodrug has been similar in
      many of the case histories we have studied and indeed similar to the approach we
      have followed. Initially, we select a suitable series of prodrug moieties, which
      either comprises totally novel structures or is deduced from the data bases
      available (bearing in mind reports of potential toxicity) or both. The successful
      preparation of these prodrugs and the studies undertaken to ensure they are of
      known purity and stability is not easy and, as would be expected, is the initial
      go/no-go decision. Usually, the next stage has involved the assessment of whether
      or not bioavailability of the parent molecule is increased after administration
      of the prodrug ester by gavage to laboratory animal species. The selection of
      which species to use has very often been made according to which has the most
      information available in those particular laboratories and in the literature. It
      is this process that can be dishearteningly misleading as was demonstrated in
      Table IV and Fig. 1. Increasing the range of animal species does not lead to a
      better ability to predict bioavailability in humans. Hydrolysis studies are
      important to ensure that any novel prodrug will hydrolyze in human tissues, and
      also in the clarification of why a particular prodrug is not performing as
      expected in animals. After selection, it is essential to determine where and how
      rapidly hydrolysis takes place in the animal species to be used for safety
      evaluation prior to the first bioavailability studies in humans. The assessment
      of absolute oral bioavailability has not always been undertaken. This would seem
      critical for studies in not only the selected animal species but also in humans.
      In the absence of these data it is difficult to judge whether oral uptake can be
      increased further by modifying the ester moieties and at the development stage to
      determine whether or not modifications in formulation could increase
      bioavailability. When the prodrug is being developed for an injectable beta
      lactam already available for humans, there would be no problem, but it would be
      an important consideration during the development of an entirely novel beta
      lactam antibiotic for which no parenteral data are available in humans. Animal
      data are not totally predictive. The development of prodrugs is not easy, as a
      consequence of species differences in the properties of the prodrug superimposed
      on those of the parent compound during the evaluation. However, technical
      advances have enabled us to assay concentrations more precisely, determine basic
      physicochemical properties more efficiently, understand absorption processes by
      the use of in vitro systems, and analyze data far more comprehensively by the use
      of ever-evolving computer software. The prodrug approach to increasing the oral
      bioavailability of beta-lactam antibiotics has provided clinically valuable
      agents and continues. Despite the inherent difficulties, knowledge gained over
      the years, of the relationships between physicochemical and biological properties
      of the parent compound and the intact prodrug ester, has contributed to the
      design of novel prodrugs and a number of novel auxiliaries have been developed.

PMID- 9760688
TI  - Hematoregulators. A case history of a novel hematoregulatory peptide, SK&F
      107647.

PMID- 9760689
TI  - Discovery and development of GG745, a potent inhibitor of both isozymes of 5
      alpha-reductase.

PMID- 9760690
TI  - Discovery of a potent and selective alpha 1A antagonist. Utilization of a rapid
      screening method to obtain pharmacokinetic parameters.

PMID- 9760691
TI  - Discovery of bioavailable inhibitors of secretory phospholipase A2.
AB  - Substrate-mimetic inhibitors of sPLA2 with submicromolar in vitro potency were
      discovered by use of a novel dual substrate screening strategy. In vivo
      evaluation of selected inhibitors in the rat carrageenan paw edema model of
      inflammation, however, indicated that in vitro potency was not a good predictor
      of in vivo activity. Studies of the metabolic stability of early examples of
      these inhibitors suggested that the metabolic lability of these compounds was a
      major contributing factor to the observed weak in vivo activity. In an attempt to
      achieve improved in vivo activity, we prepared and tested compounds designed to
      overcome the observed metabolic instability. The design of the new compounds
      involved two types of changes in the inhibitor molecules. First, the C-2 ester
      moiety was replaced with an amide function so that direct cleavage by stomach
      acid and blood esterases at this site was minimized. Second, omega-oxidation of
      the decanamide moiety was eliminated by substitution of hydrogen with fluorine in
      this position. Compounds containing fluorine in the terminal positions of the
      alkyl chain retained sPLA2 inhibitory activity and also possessed improved in
      vitro metabolic stability and pharmacokinetic parameters relative to
      nonfluorinated inhibitors in this series. As exemplified by GW 4776, improvements
      in metabolic stability alone, however, were not sufficient to ensure oral
      activity. Thus, GW 4776 did not show oral activity in the carrageenan edema model
      and had only modest activity after i.v. dosing in the same model. In fact, the
      results for GW 9624 and GW 8219 suggested that factors in addition to potency of
      sPLA2 inhibition and metabolism affect the observed in vivo activity. Despite the
      fact that these two compounds varied only by a single oxygen-to-sulfur
      substitution, one was active whereas the other was not. One possible explanation
      for the observed variability is a compound-dependent difference in the rate of
      equilibration into tissue. This possibility is relevant as both the carrageenan
      paw edema model and the phorbol ester edema model involve a localized
      inflammation. No measurements were made to assess differences in the distribution
      of the different inhibitors between the blood and the localized site of
      inflammation. In summary, a series of bioavailable inhibitors of sPLA2 was
      prepared using an iterative approach that combined medicinal chemistry, in vitro
      and in vivo evaluation of biological activity, and metabolic and pharmacokinetic
      studies. Although some compounds in the series showed in vivo activity, the anti
      inflammatory effect observed in animal models was modest and a decision was made
      to abandon sPLA2 as a molecular target for the development of anti-inflammatory
      agents.

PMID- 9760692
TI  - The anxieties of drug discovery and development. CCK-B receptor antagonists.

PMID- 9760693
TI  - CI-1015. An orally active CCK-B receptor antagonist with an improved
      pharmacokinetic profile.

PMID- 9760694
TI  - Orally active nonpeptide CCK-A agonists.

PMID- 9760695
TI  - Orally active growth hormone secretagogues.

PMID- 9760696
TI  - Dorzolamide, a 40-year wait. From an oral to a topical carbonic anhydrase
      inhibitor for the treatment of glaucoma.
AB  - Dorzolamide, on the basis of its pharmacological profile and lack of undesirable
      side effects in safety assessment studies together with the fact that it could be
      formulated in solution at 2%, underwent extensive clinical studies. Early
      clinical studies in the development of dorzolamide have been described elsewhere
      (Maren, 1995; Serle and Podos, 1995). In a 1-year study in which a comparison was
      undertaken in patients for intraocular pressure lowering effects between 2%
      dorzolamide administered three times daily, 0.5% betaxolol twice daily, and 0.5%
      timolol twice daily, the peak reductions in intraocular pressure were 23, 21, and
      25%, respectively. Tachyphylaxis did not develop to dorzolamide nor were
      electrolyte and/or systemic side effects encountered (Strahlman et al., 1995).
      The latter is consistent with results of a pharmacokinetic study in humans in
      which plasma levels of dorzolamide were lower than the limit of detection (5
      ng/ml) at a time when the red blood cell content of dorzolamide had reached
      steady state which was appreciably less than the red blood cell content of the
      enzyme (Biollaz et al., 1995). Patients taking 0.5% timolol twice daily received
      either 2% dorzolamide twice daily or 2% pilocarpine four times daily for 6 months
      and the additional reductions in intraocular pressure elicited by dorzolamide and
      pilocarpine were very similar. However, pilocarpine usage resulted in a higher
      discontinuation rate (Strahlman et al., 1996). In a separate study in which
      dorzolamide and pilocarpine were compared at these dosage schedules, patients
      preferred dorzolamide to pilocarpine by a ratio of over 7 to 1 in terms of
      quality of life (Laibovitz et al., 1995). In summary, the quest for a topical,
      ocular hypotensive, CA inhibitor, though time-consuming, was a successful one
      with the introduction of dorzolamide into general clinical practice.

PMID- 9760697
TI  - Discovery and development of novel melanogenic drugs. Melanotan-I and -II.

PMID- 9760698
TI  - Experimental strategies to promote axonal regeneration after traumatic central
      nervous system injury.
AB  - A damage or pathological process that destroys the continuity of axons in the
      mature central nervous system (CNS) has devastating consequences and produces
      lasting functional deficits. One of the major challenges in this field is to
      stimulate the regrowth of severed axons and reconstruction of pathways. Recent
      progress in molecular and cell biology has resulted in an explosion of knowledge
      on factors in the adult CNS being nonsupportive or even actively inhibitory to
      axonal regrowth. The new findings have a strong impact on the development of new
      therapeutic concepts directed to stimulate axonal regeneration. They give rise to
      cautious optimism, showing that under some circumstances repair of a CNS lesion
      is possible. In this review the authors summarize the current knowledge on the
      factors and mechanisms involved in regeneration failure and provide an overview
      of the current therapeutic approaches that may enable effective CNS regeneration
      in the future.

PMID- 9760699
TI  - Inflammation and glial responses in ischemic brain lesions.
AB  - Focal cerebral ischemia elicits a strong inflammatory response involving early
      recruitment of granulocytes and delayed infiltration of ischemic areas and the
      boundary zones by T cells and macrophages. Infiltration of hematogenous
      leukocytes is facilitated by an upregulation of the cellular adhesion molecules P
      selectin, intercellular adhesion molecule-1 and vascular adhesion molecule-1 on
      endothelial cells. Blocking of the leukocyte/endothelial cell adhesion process
      significantly reduces stroke volume after transient, but not permanent middle
      cerebral artery occlusion. In the infarct region microglia are activated within
      hours and within days transform into phagocytes. Astrocytes upregulate
      intermediate filaments, synthesize neurotrophins and form glial scars. Local
      microglia and infiltrating macrophages demarcate infarcts and rapidly remove
      debris. Remote from the lesion no cellular infiltration occurs, but astroglia and
      microglia are transiently activated. Astrocytic activation is induced by
      spreading depression. In focal ischemia neurons die acutely by necrosis and in a
      delayed fashion by programmed cell death, apoptosis. Proinflammatory cytokines
      such as tumor necrosis factor-alpha and interleukin-1 beta are upregulated within
      hours in ischemic brain lesions. Either directly or via induction of neurotoxic
      mediators such as nitric oxide, cytokines may contribute to infarct progression
      in the post-ischemic period. On the other hand, inflammation is tightly linked
      with rapid removal of debris and repair processes. At present it is unclear
      whether detrimental effects of inflammation outweigh neuroprotective mechanisms
      or vice versa. In global ischemia inflammatory responses are limited, but micro-
      and astroglia are also strongly activated. Glial responses significantly differ
      between brain regions with selective neuronal death and neighbouring areas that
      are more resistent to ischemic damage.

PMID- 9760700
TI  - The origin and differentiation of microglial cells during development.
AB  - Some authors claim that microglia originate from the neuroepithelium, although
      most now believe that microglial cells are of mesodermal origin, and probably
      belong to the monocyte/macrophage cell line. These cells must enter the
      developing central nervous system (CNS) from the blood stream, the ventricular
      space or the meninges. Afterward microglial cells are distributed more or less
      homogeneously through the entire nervous parenchyma. Stereotyped patterns of
      migration have been recognized during development, in which long-distance
      tangential migration precedes radial migration of individual cells. Microglial
      cells moving through the nervous parenchyma are ameboid microglia, which
      apparently differentiate into ramified microglia after reaching their definitive
      location. This is supported by the presence of cells showing intermediate
      features between those of ameboid and ramified microglia. The factors that
      control the invasion of the nervous parenchyma, migration within the developing
      CNS and differentiation of microglial cells are not well known. These phenomena
      apparently depend on environmental factors such as soluble or cell-surface bound
      molecules and components of the extracellular matrix. Microglial cells within the
      developing CNS are involved in clearing cell debris and withdrawing misdirected
      or transitory axons, and presumably support cell survival and neurite growth.

PMID- 9760701
TI  - The cerebellum in the spatial problem solving: a co-star or a guest star?
AB  - The experimental findings reviewed here indicate that the cerebellum has to be
      added to the regions known to be involved in the spatial learning. Cerebellar
      function is specifically linked to 'how to find an object' rather than 'where the
      object is in the space'. In the Morris water maze (MWM) hemicerebellectomized
      (HCbed) rats displayed a severe impairment in coping with spatial information,
      displaying only peripheral circling. And yet, when the MWM cue phase was
      prolonged, HCbed rats succeeded in acquiring some abilities to learn platform
      position, even in a pure place paradigm, such as finding a hidden platform with
      the starting points sequentially changed. Conversely, whether the searching
      strategy was acquired preoperatively, no exploration deficit appeared. Thus,
      cerebellar lesions appear to affect the procedural components of spatial
      function, sparing the declarative ones. When intact animals were non-spatially
      pre-trained and then HCbed, they exhibited an expanded scanning strategy,
      underlining the cerebellar involvement in procedural component acquisition. By
      testing HCbed rats in an active avoidance task, first without and then with a
      request for right/left discrimination, lesioned rats displayed severe deficits.
      Thus, besides a marked impairment in facing procedural components of spatial
      processing, cerebellar lesion provokes deficits also in right/left discrimination
      task. In conclusion, it is possible to propose the cerebellum as one part of a
      large system that includes frontal, posterior parietal, inferior temporal
      cortices, hippocampus and basal ganglia. These structures form an allocentric
      spatial system and an egocentric control system, that interlock to process the
      information involved in representing an object in the space.

PMID- 9760702
TI  - The effects of Aconitum alkaloids on the central nervous system.
AB  - Preparations of Aconitum roots are employed in Chinese and Japanese medicine for
      analgesic, antirheumatic and neurological indications. The recent surge in use of
      phytomedicine derived from traditional Chinese medicine as well as increasing
      concerns about possible toxic effects of these compounds have inspired a great
      deal of research into the mechanisms by which certain Aconitum alkaloids may act
      on the central nervous system. The pharmacological effects of preparations of
      Aconitum roots are attributed to several diterpenoid alkaloids. The main alkaloid
      of these plants is aconitine, a highly toxic diterpenoid alkaloid which is known
      to suppress the inactivation of voltage-dependent Na+ channels by binding to
      neurotoxin binding site 2 of the alpha-subunit of the channel protein. In this
      article the pharmacology of several structurally related Aconitum alkaloids is
      highlighted and their therapeutic vs toxic potential is discussed. Neurochemical
      and neurophysiological studies will be reviewed with emphasis on the effects of
      the alkaloids in regions of the brain that have been implicated in pain
      transmission and generation of epileptic activity. Considering the chemical
      structure of the Aconitum alkaloids as well as their mechanism of action, a
      subdivision in three groups becomes obvious: the first group comprises such
      alkaloids which possess high toxicity due to two ester boundings at the diterpene
      skeleton. The members of this group activate voltage-dependent sodium channels
      already at resting potential and inhibit noradrenaline reuptake. Activation of
      sodium channels and in consequence excessive depolarization with final
      inexcitability and suppression of pain transmission account for their
      antinociceptive properties. The second group comprises less toxic monoesters
      which have been shown to possess strong antinociceptive, antiarrhythmic and
      antiepileptiform properties due to a blockade of the voltage-dependent sodium
      channel. Electrophysiological studies have revealed a use-dependent inhibition of
      neuronal activity by these alkaloids. They seem to be competitive antagonists of
      the group I-alkaloids. The third group of Aconitum alkaloids are lacking an ester
      side chain in the molecule. Toxicity is markedly reduced when compared with the
      two other groups. They fail to affect neuronal activity, but are reported to have
      antiarrhythmic actions suggesting that they may have different affinities to
      various subtypes of the alpha-subunit of the Na+ channel in brain and heart.

PMID- 9760703
TI  - Release of neurotransmitters in the locus coeruleus.
AB  - In the past 15 years the release of neurotransmitters and their metabolites in
      the locus coeruleus (LC) has been studied by using three approaches:
      microdialysis; push-pull superfusion; and voltammetry. These sophisticated
      techniques, which render it possible to follow the time course and magnitude of
      neurochemical changes in anaesthetized and conscious animals, have permitted
      great strides towards understanding neurotransmission in the LC. It appears that
      noradrenaline, known to be released in distant terminal fields, is also released
      in the somatodendritic area of LC neurons in response to drugs and physiological
      stimuli. Furthermore, determination of in vivo release enables the identification
      of functionally important neurotransmitter systems involved in relaying and
      integrating information reaching the LC via afferent neurons. As outlined in this
      review, the release rates of glutamate, aspartate, gamma-aminobutyric acid,
      glycine, 5-hydroxytryptamine and catecholamines, are modified in particular by
      arousing and stressful stimuli, pain, changes in cardiovascular homeostasis, as
      well as during opioid withdrawal or the sleep-wake-cycle. Profound interactions
      also occur between some of the neurotransmitters released during these
      situations. It appears that individual stimuli produce distinct neurochemical
      changes which contribute to the regulation of neuronal LC activity. Stimuli that
      activate LC neurons, such as pain, fall of blood pressure, noise, opiate
      withdrawal, do not produce a uniform response but modality-specific release
      patterns of excitatory and inhibitory neurotransmitters within the LC. From these
      studies and from existing neuroanatomical and electrophysiological data our
      knowledge of how neurotransmitters work in concert to regulate the functional
      state of LC noradrenergic perikarya in physiological and pathophysiological
      conditions is just emerging.

PMID- 9760704
TI  - Potent suppressive activity of chlorophyll a and b from green tea (Camellia
      sinensis) against tumor promotion in mouse skin.
AB  - Potent antigenotoxic and anti-tumor promoting activities of chlorophyll a from
      green tea (camellia sinensis) have been shown using in vitro cell culture
      experiments (Okai Y. et al. (1996) Mutation Res., 370, 11-17). In the present
      study, the authors analyzed in vivo effects of chlorophyll a and b from green tea
      on tumor promotion in mouse skin in the following ways. 1. When chlorophyll a and
      b from green tea were applied before each treatment by a tumor promoter, 12-O
      tetradecanoyl-phorbol-13-acetate (TPA) on BALB/c mouse skin initiated by 7, 12
      dimethylbenz [a] an-thracene (DMBA), they caused significant suppression in a
      dose-dependent manner against BALB/c mouse skin tumorigenesis. 2. Chlorophyll a
      and b showed significant suppressive effects against TPA-induced inflammatory
      reaction such as edema formation in BALB/c mouse ear skin in a dose-dependent
      fashion. These results suggest that chlorophyll a and b possess potent
      suppressive activities against tumor promotion in mouse skin.

PMID- 9760705
TI  - [AHP analysis of activities expected of public health nurses at a public health
      center].
AB  - The activities expected of Public Health Nurses (PHN) at a Public Health Center
      (PHC) were evaluated by the AHP technique based on the results of a Focus Group
      Discussion among 7 PHNs working in K PHC, Fukuoka. Among the five PHN activities,
      "Collection and analysis of information" was evaluated as the most important,
      followed by "Consultation", "Coordination of different sectors", "Control and
      support of patients with chronic diseases", and "Health education for the
      public". However, the investigated PHNs concluded that their knowledge of and
      skill in doing "Collection and analysis of information" are insufficient. It is
      therefore recommended that continuous training courses on statistics and
      epidemiology be organized for the PHNs.

PMID- 9760706
TI  - [A plan of the life-long learning support system of UOEH--possibility for the
      introduction of distance learning system by the Internet].
AB  - In order to keep up with the rapid advance in knowledge and skills in various
      industrial sectors, the needs for the life-long learning has increased recently.
      This is also the case for the University of Occupational and Environmental
      Health, Japan, which has as its aim the education of occupational health
      specialists. In fact, there are many universities and colleges which have
      organized some post-graduate courses for the workers. However, most of these
      courses are for workers who can come to classes in the daytime or evening. In the
      case of UOEH, it is not enough to organize such type of classes in order to
      respond to the social needs, because it has to offer an opportunity of life-long
      learning for all occupational health specialists in all parts of Japan. In order
      to solve this problem, it is recommended that a distance learning system based on
      modern information technology such as the internet be organized. In this report,
      the authors present the distance learning system of Wisconsin University in the
      USA, and that of Tamagawa Gakuen University of Japan. After evaluating these two
      systems, a plan for a life-long learning support system of UOEH is suggested,
      which consists of a distance learning system based on the internet.

PMID- 9760707
TI  - [Trends of the biological monitoring measurements from 1991 to 1995].
AB  - Partial amendments to the Japanese Regulation on the Prevention of Lead Poisoning
      and that of Organic Solvent Poisoning were made in 1989. As a result, the
      measurement of blood lead and urinary delta-aminolevulinic acid (delta-ALA)
      became indispensable items of the occupational health examination for workers who
      handle lead. Also, the measurement of urinary metabolites of workers who handle
      eight kinds of organic solvents (xylene, N,N-dimethylformamide, styrene,
      tetrachloroethylene, 1,1,1-trichloroethane, trichloroethylene, toluene, and
      normal-hexane) became mandatory. The results of the biological monitoring
      mentioned above are classified into one of three categories, that is,
      distribution 1, 2 and 3, according to the concentration of the determinants. In
      this paper, the incidence of distribution 1, 2 and 3 of each determinant is
      reported and its change from 1991 to 1995 is discussed. The incidence of
      distribution 3 was 0.1-5.0% in each determinant. Although the ratio of
      distribution 1, 2 and 3 seems to have been almost the same for 5 years some
      determinants decreased their percentage of distribution 3. It is important to
      utilize the biological monitoring results for the improvement of working
      environments and working styles, and health management.

PMID- 9760708
TI  - [Expertise in occupational health nursing (II)--Report on the 17th UOEH
      International Symposium].
AB  - Three hundred and fifty-two OHNs and collaborative persons from 17 countries and
      the ILO assembled at UOEH to participate in the 17th UOEH International Symposium
      to commemorate the inauguration of the UOEH School of Health Sciences from
      October 20 to 22, 1997. The main theme of this Symposium was "Occupational Health
      Nurse (OHM) Expertise." The Symposium was opened by greetings from Dr. Akira
      Koizumi, followed by a message from ILO presented by Dr. G.H. Cappee, head of the
      Medical Section Occupational Safety & Health Branch, ILO. Dr. Bonnie Rogers of
      North Carolina University, Chapel Hill, and President of AAOHN, lectured on the
      main theme of the Symposium, and Dr. M.A. Fingerhut gave a lecture on
      "Partnership in Occupational Safety and Health." At the general sessions, 5
      themes were discussed.--1) Partnership in Occupational Health, 2) Education and
      Training of OHNs, 3) Intervention/Behavior to Disease Prevention and Health
      Promotion, 4) How to Integrate Computing into Occupation Health Nursing and 5)
      Cost/Benefit Effectiveness of Occupational Health Nursing. For all 5 sessions,
      there were keynote lectures, oral and poster presentations. This report reviews
      the lectures by Dr. B. Rogers on "Expertise in Occupational Health Nursing," by
      Dr. Kuchinski on "Education and Training of Occupational Health Nurses in The
      US," the presentation by Mrs. J. Fanchette, DIUST/GIT Service de Pathologie
      Professionnelle Hospital Civil, France, on "Evaluation of An Interuniversity
      Diploma Course Occupational Health Nurse Qualification," by Dr. K. June,
      Soonchunhyang Univ., Korea, on "Transition of Occupational Health Nursing
      Education in Korea" and finally, the lecture by Dr. F. Mitsuhashi on "Revisions
      in the Industrial Safety and Health Law and Expected Models for Occupational
      Health Nursing Staff."

PMID- 9760709
TI  - [Is subjective health status a good predictor of work resumption?].
AB  - The aim of the study is to investigate how persons with long term work-disability
      due to low back pain assess their health status and how the subjective health
      measurement influence work resumption (n = 663). Information on their subjective
      health status at 42 days after start of work-disability is set in relation to the
      outcomes "Continued work disability after 84 days" versus "work resumption". Bi-
      and multivariate analysis show that information on the subjective health status
      and the subjective work prognosis differs between both groups already after 42
      days. The results show that the subjective health status in connection with the
      subjective work prognosis is a good predictor for "Non-resumption of work", but
      not a sufficiently good predictor for "Resumption to work".

PMID- 9760710
TI  - [Economic evaluation in a trial of medically controlled prescription of narcotics
      to dependent users (PROVE)].
AB  - In the 1994-1996 trial of medically controlled prescription of narcotics to
      dependent users, 800 places were ascribed to heroin substitutes and another 200
      for methadone and morphine substitutes. The trial was evaluated with the aid of
      an accompanying research. Among the results demonstrated in the evaluation was an
      improvement of the health of the participants. The economic assessment was drawn
      from observations of health effects within a sub-sample of 142 participants from
      four centers. In a retrospective statistical survey, for each acute illness which
      could be influenced through the trial, the number of diagnoses was recorded in
      the first and thirteenth month after study entry. Also, based on a number of
      representative cases for each of these acute illnesses, the resource use, i.e.
      the types and numbers of medical products and services rendered to the patients,
      was recorded. The results showed a clear decline in depressive episodes, skin
      diseases, digestive system disorders as well as epileptic attacks and
      intoxication. Treatment costs could be reduced from a total of CHF 94875.--to CHF
      21,998.--/month or from CHF 22.27 to CHF 5.15/patient per day. The improvement of
      somatic and psychic health due to the medically controlled prescription of
      narcotics resulted in a benefit of CHF 17.11/person per day.

PMID- 9760711
TI  - [Fractures in the elderly: are postal questionnaires sufficiently sensitive?].
AB  - Within the European Prospective Osteoporosis Study the validity of a postal
      questionnaire concerning fractures in the elderly was assessed. A sample of 144
      men and women aged 50 to 84 hospitalized in an urban hospital due to fractures
      within the past 12 months was investigated. Eight percent of the respondents
      denied any recent fracture and turned out to be false negatives, less than
      previously recorded. Mode and frequency of questioning seem to influence the
      results. To assess fracture localisation, we used a graphical method (mannequin).
      Due to various factors, one third of all localisations were incorrect.

PMID- 9760712
TI  - Parturient haemoglobinuria in buffaloes--a review.
AB  - Parturient haemoglobinuria is a disease of economic importance in buffalo rearing
      countries in general and in India, Pakistan and Egypt in particular. This study
      reviews the information on aetiology, epidemiology, clinical aspects and
      treatment of parturient haemoglobinuria in buffaloes. The body of literature
      reviewed suggests that phosphorus deficiency in the diet of affected animals
      plays a major role in causing this disease, although the precise mechanism
      involved is complex. The possible factors involved and their interplay, plus the
      clinical picture of affected animals and the results of different preventive and
      therapeutic regimes are discussed. The study also identifies areas for further
      research.

PMID- 9760713
TI  - Control of foot-and-mouth disease through vaccination and the isolation of
      infected animals.
AB  - Foot-and-mouth disease (FMD) within Saudi Arabian dairy herds has been controlled
      for the past decade through vaccination. Data from 19 outbreaks on Saudi farms
      has suggested that the durability of these vaccines extended for 2.5 months,
      providing an 81-98% level of protection. Vaccination has nevertheless failed to
      prevent the establishment and sometimes persistence of the disease. This is
      probably because the highly contagious nature of FMD creates increasing levels of
      viral excretion during an outbreak, and the co-habitation in Saudi farms of
      affected/susceptible animals following diagnosis, predisposes the herds to re
      infection. Pre-clinical excretion of the virus leads to the infection of
      additional in-contact susceptible animals prior to diagnosis, so the isolation of
      clinically infected animals does not guarantee a removal of infection. Saudi
      Arabian farms are subdivided into managed farm pens and isolation (away from the
      farm) of all animals in infected pens not only removes the infectious individuals
      showing clinical signs, but also those that are sub-clinical and excreting virus.
      Simulations suggest that removing all infectious animals from the herd
      significantly reduces the per cent infected in the herd.

PMID- 9760714
TI  - Evaluation of hyperimmune sera against goat pox viral antigens.
AB  - Laboratory diagnosis of goat poxvirus (GPV) requires suitable diagnostic reagents
      (sera and antigens). GPV-infected scab suspension has been used as antigen for
      production of hyperimmune sera (HIS) by several workers (Pandey and Singh, 1972;
      Tantawi et al., 1980; Sharma et al., 1988). This antiserum sometimes reacts non
      specifically in routine laboratory tests such as the agar gel precipitation test
      (AGPT) and counter-immunoelectrophoresis (CIE) (Sharma et al., 1988). Production
      of specific goat pox antiserum involves its adsorption with healthy goat-skin
      triturate. The present work evaluated various HIS raised against different
      antigens of GPV in order to develop an antiserum for laboratory diagnosis of goat
      pox infections without any non-specificity.

PMID- 9760715
TI  - Isolation of Mycobacterium species from raw milk of pastoral cattle of the
      Southern Highlands of Tanzania.
AB  - A study to determine the secretion of Mycobacterium spp. in milk from indigenous
      cattle was carried out in pastoral cattle reared in the Southern Highlands to
      Tanzania. The study was aimed at elucidating the dangers associated with milk
      borne zoonoses in a society where milk is normally consumed raw. Out of 805 milk
      samples, 31 (3.9%) were positive for mycobacteria. There was a preponderance of
      atypical mycobacteria (87%) whereas only two isolates (6.5%) were confirmed as M.
      bovis. Atypical mycobacteria included: M. terrae (n = 7), M. fortuitum (n = 2),
      M. flavescens (n = 13), M. gordonae (n = 1) and M. smegmatis (n = 4). Although
      the number of M. bovis positive samples was low, the habit of pooling milk may
      still pose great public health dangers to milk consumers in this part of the
      world. Moreover, isolation of atypical mycobacteria should also be considered to
      be a danger to human health in countries such as Tanzania, where the number of
      people with lowered immunity due to HIV infection is on the increase.

PMID- 9760716
TI  - Getah virus infection of Indian horses.
AB  - An outbreak of disease, characterized by depression, anorexia, fever, limb oedema
      and lymphocytopenia, occurred on a farm for thoroughbreds in India in 1990.
      Twenty-six of the 88 horses on the farm were affected, predominantly adults.
      Signs were present in affected horses for 7-10 days, and the outbreak lasted 21
      days. Seven of the 26 affected horses were tested for exposure to Getah virus
      using paired serum samples, acute and convalescent. Four of the 7 horses
      seroconverted to Getah virus, and the other three showed a 4-fold or greater rise
      in titre. The clinical and laboratory findings were similar, but not indentical,
      to those described in natural and experimental infections in Japanese horses.
      This is the first description of disease caused by Getah virus infection in
      horses outside Japan. In addition serum samples from 152 horses from 3 regions of
      India were evaluated for the presence of antibodies to Getah virus. The
      seroprevalence was found to be 17%, indicating exposure to the virus elsewhere in
      Indian horses.

PMID- 9760717
TI  - Comparative evaluation of IHA and CIEP in the diagnosis of Toxocara vitulorum in
      pregnant cows and buffaloes.

PMID- 9760718
TI  - Prospects and strategies for genetic improvement of the dairy potential of
      tropical cattle by selection.
AB  - The import of genetic material and the use of crossbreeding to improve the dairy
      merit of tropical cattle has been criticized for eroding the livestock genetic
      resources of the tropics. An alternative is genetic improvement of the indigenous
      cattle through selection. The objective of the present paper is to examine the
      feasibility of this alternative. Constraints to genetic improvement of tropical
      cattle through selection are discussed. Low reproductive rates and high calf
      mortality reduce the intensity of selection. The generation interval, which is
      long in cattle, is further prolonged by the late sexual maturity and the long
      calving intervals in most tropical breeds. The most serious constraint is,
      however, that the extensive milk recording schemes which support dairy cattle
      breeding programmes in many temperate countries are almost non-existent in the
      tropics. In this situation, the most realistic approach to improvement through
      selection is to start with a single nucleus herd (or a group of cooperating
      herds). Two alternative selection programmes (with and without progeny testing)
      for a closed herd of 500 cows are outlined. The alternative which assumed no
      progeny testing, i.e. selection of bulls on pedigree information only, gave the
      fastest genetic improvement (predicted at 36 kg/year). By distributing breeding
      bulls from the herd the genetic progress can be disseminated to the outside
      population with a time lag of about two generations. A nucleus herd can supply
      about 15 selected bulls per 100 cows in the herd per year, enough for a
      population of several thousand cows.

PMID- 9760719
TI  - 3,4-Bis(1-adamantyl)-1,2-dithiete: the first structurally characterized dithiete
      unsupported by a ring or benzenoid frame.
AB  - The structure determination of 3,4-bis(1-adamantyl)-1,2-dithiete, (C10H15)2C2S2
      or C22H30S2, reported herein is the first crystallographic characterization of a
      1,2-dithiete molecule unsupported by a benzenoid frame. Two independent molecules
      exist in the asymmetric unit separated by a pseudo-inversion center. The S2C2
      four-membered dithiete ring is planar, with a trapezoidal shape enforced by the
      longer disulfide bond [average 2.086 (2) A] compared with the olefinic bond
      [average 1.363 (6) A]. The adamantyl substituents differ from one another by
      adopting slightly different rotational conformations with respect to the dithiete
      ring. The quaternary C atoms of the adamantyl groups deviate only slightly from
      the plane of the dithiete ring (average displacement of 0.023 A).

PMID- 9760720
TI  - Ortho-(1-naphthoyl)benzoic acid.
AB  - The title acid, C18H12O3, crystallized in the centrosymmetric space group C2/c
      and exhibits carboxyl group hydrogen bonding of the cyclic dimer type about a
      center of symmetry. The Odonor-Oacceptor distance in the hydrogen bond is 2.692
      (2) A. In addition, seven C-H groups and the three O atoms in the molecule are
      involved in significantly attractive C-H...O interactions with 11 neighbors,
      forming a three-dimensional network. The carboxylic H atom is ordered, as are the
      carboxylic O atoms.

PMID- 9760721
TI  - The RNA folding problem: a variational problem within an adiabatic approximation.
AB  - Biopolymer folding is an expeditious process taking place within timescales
      incommensurably shorter than ergodic times. Furthermore, its robustness suggests
      that the process must depend on a relatively coarse level of resolution of
      conformation space. To account for these features while focusing on the RNA
      context, we derive a variational principle formulated within an adiabatic
      approximation obtained by integrating out fast-relaxing molecular motions.
      Folding pathways are generated by means of a stochastic process which begets a
      least effort principle reflecting a stepwise minimization of the conformational
      entropy cost for each folding event with concurrent maximization of the base
      pairing. This economy of the process is found to have kinetic consequences if we
      treat base-pairing contact patterns (BPPs) adiabatically, that is, as quasi
      equilibrium states: the probability distribution of overall folding timespans
      associated to the process resolved at the BPP level is maximized at the
      brachistochrone or overall least-time pathway for functionally-competent RNAs. In
      turn, this pathway is shown to yield all the phylogenetically-conserved
      structural features of the active conformation within biologically-relevant
      timescales.

PMID- 9760722
TI  - Calculation of concentrations of equilibrium components in an in vitro activity
      test of vancomycin antibiotics and the possible mode of action.
AB  - The vancomycin group of antibiotics is considered to act by binding the bacterial
      cell wall mucopeptide precursor terminating in -L-Lys-D-Ala-D-Ala. The
      dimerization of these antibiotics is also believed to play a role in the action.
      In this paper, we analyzed the equilibria in the in vitro antibacterial activity
      test of the vancomycin antibiotics both with and without the cell wall precursor
      analogue di-acetyl-L-Lys-D-Ala-D-Ala (DALAA). Based on the equilibria and
      concentration balance, we obtained 10 equations (seven quadratic equations and
      three linear equations) containing 10 equilibrium concentrations which relate to
      the antibiotic, cell wall precursor and DALAA. A computer program was written to
      solve these equations from known dimerization constant and the binding constants
      (both monomer and dimer) with DALAA of the antibiotic. The concentrations in the
      test for vancomycin and eremomycin were obtained. The antibiotic activity of
      these antibiotics may be quantitatively correlated with their dimerization
      constants and the binding constants through the calculation. By analyzing the
      calculated results, we concluded that the cell wall-bound dimer may be the major
      contributor to the antibiotic activity in the case of eremomycin, while the cell
      wall-bound monomer is possibly the determinant for the activity of vancomycin.

PMID- 9760723
TI  - Excess counterion binding and ionic stability of kinked and branched DNA.
AB  - We compute the excess number of counterions associated with kinked and branched
      DNA, and the ionic stabilities of these structures as a function of chain length
      and both sodium and magnesium salt concentration, using numerical counterion
      condensation theory. The DNA structures are modeled as two or more finite lines
      of phosphate charges radiating from the kink or junction center. The number of
      excess counterions around the (40-90 degrees) kinked duplex is very small (at
      most four). The geometries of large three- and four-way DNA junctions (with > 50
      base pairs per arm) in solutions containing low to moderate NaCl concentrations,
      by contrast, accumulate a substantial number of excess sodium ions (> 20) but no
      more than 15 magnesium counterions. The excess number of counterions surrounding
      the kinked linear chain and the branched DNA structures either remains invariant
      or increases with chain length, tending to reach a plateau value. Open
      configurations, such as the planar Y-shaped three-way junction (with three 120
      degrees inter-arm angles) and the 90 degrees cross-shaped four-way junction, are
      ionically more stable than compact geometries, such as pyramidal three-way
      junctions and X-shaped four-way junctions, over the entire range of salt
      concentration considered (10(-5)-10(-1) M NaCl or MgCl2). The ionic stabilities
      of the compact forms increase with increasing salt concentration and become
      comparable to those of the extended geometries at high salt (especially when
      magnesium is the supporting salt).

PMID- 9760724
TI  - New insights into microtubule structure and function from the atomic model of
      tubulin.
AB  - The structure of tubulin has recently been solved by electron crystallography of
      zinc-induced tubulin sheets. Because tubulin was studied in a polymerized state,
      the model contains information on the interactions between monomers that give
      rise to the alpha beta dimer as well as contacts between adjacent dimers that
      result in the structure of the protofilament. The model includes the binding site
      of taxol, an anti-cancer agent that acts by stabilizing microtubules. The present
      tubulin model gives the first structural framework for understanding microtubule
      polymerization and its regulation by nucleotides and anti-mitotic drugs at the
      molecular level.

PMID- 9760725
TI  - General features of the recognition by tubulin of colchicine and related
      compounds.
AB  - The kinetic mechanisms of the binding to tubulin of colchicine and eight
      different analogues have been studied to elucidate details of the recognition
      mechanism. All of the analogues follow a two step binding mechanism i.e. binding
      occurs via an initial step with low affinity, followed by an isomerisation of the
      initial complex leading to the final high affinity state. For several analogues
      the kinetic and thermodynamic data of both processes are compared here. For all
      the analogues the delta G1 degree of initial binding at 25 degrees C varies
      between -13.3 and -28.8 kJ. mol-1. For the second step delta G2 degrees varies
      between -2.4 and -27 kJ. mol-1. These limited ranges of free energy change are,
      however, obtained by a great variety of enthalpy changes and compensatory entropy
      changes. Comparison of the data for the first and second steps indicates that
      structural alterations of the drugs always change the thermodynamic parameters of
      the two steps, and the changes in the first and the second steps are in opposite
      directions. The fact that this range of experimental behaviour can be
      incorporated into a general mechanism encourages the extension of these
      investigations to other colchicine analogues and related compounds with potential
      pharmaceutical applications.

PMID- 9760726
TI  - Organisation and structure of microtubules and microtubule-motor protein
      complexes.
AB  - We present a short overview of the current status of work on the organisation and
      structure of microtubules and of microtubule-motor protein complexes. At present
      there is great interest in obtaining structural information that can help us to
      understand the movement of the kinesin family of microtubule associated molecular
      motors. Using electron cryomicroscopy and image reconstruction methods three
      dimensional maps of microtubule-motor complexes have been obtained in the
      presence of different nucleotides. We address a number of principles involved in
      different aspects of this work.

PMID- 9760727
TI  - Conformations of kinesin: solution vs. crystal structures and interactions with
      microtubules.
AB  - Recently, the molecular structures of monomeric and dimeric kinesin constructs in
      complex with ADP have been determined by X-ray crystallography (Kull et al. 1996;
      Kozielski et al. 1997 a; Sack et al. 1997). The "motor" or "head" domains have
      almost identical conformations in the known crystal structures, yet the kinesin
      dimer is asymmetric: the orientation of the two heads relative to the coiled-coil
      formed by their neck regions is different. We used small angle solution
      scattering of kinesin constructs and microtubules decorated with kinesin in order
      to find out whether these crystal structures are of relevance for kinesin's
      structure under natural conditions and for its interaction with microtubules. Our
      preliminary results indicate that the crystal structures of monomeric and dimeric
      kinesin are similar to their structures in solution, though in solution the
      center-of-mass distance between the motor domains of the dimer could be slightly
      greater. The crystal structure of dimeric kinesin can be interpreted as
      representing two equivalent conformations. Transitions between these or very
      similar conformational states may occur in solution. Binding of kinesin to
      microtubules has conformational effects on both, the kinesin and the microtubule.
      Solution scattering of kinesin decorated microtubules reveals a peak in intensity
      that is characteristic for the B-surface lattice and that can be used to monitor
      the axial repeat of the microtubules under various conditions. In decoration
      experiments, dimeric kinesin dissociates, at least partly, leading to a
      stoichiometry of 1:1 (one kinesin head per tubulin dimer; Thormahlen et al.
      1998a) in contrast to the stoichiometry of 2:1 reported for dimeric ncd. This
      discrepancy is possibly due to the effect of steric hindrance between kinesin
      dimers on adjacent binding sites.

PMID- 9760728
TI  - The role of the dynein stalk in cytoplasmic and flagellar motility.
AB  - We have recently identified a microtubule binding domain within the motor protein
      cytoplasmic dynein. This domain is situated at the end of a slender 10-12 nm
      projection which corresponds to the stalks previously observed extending from the
      heads of both axonemal and cytoplasmic dyneins. The stalks also correspond to the
      B-links observed to connect outer arm axonemal dyneins to the B-microtubules in
      flagella and constitute the microtubule attachment sites during dynein motility.
      The stalks contrast strikingly with the polymer attachment domains of the
      kinesins and myosins which are found on the surface of the motor head. The
      difference in dynein's structural design raises intriguing questions as to how
      the stalk functions in force production along microtubules. In this article, we
      attempt to integrate the myriad of biochemical and EM structural data that has
      been previously collected regarding dynein with recent molecular findings, in an
      effort to begin to understand the mechanism of dynein motility.

PMID- 9760729
TI  - Fluctuation driven transport and models of molecular motors and pumps.
AB  - Non-equilibrium fluctuations can drive vectorial transport along an anisotropic
      structure in an isothermal medium by biasing the effect of thermal noise (kBT).
      Mechanisms based on this principle are often called Brownian ratchets and have
      been invoked as a possible explanation for the operation of biomolecular motors
      and pumps. We discuss the thermodynamics and kinetics for the operation of
      microscopic ratchet motors under conditions relevant to biology, showing how
      energy provided by external fluctuations or a non-equilibrium chemical reaction
      can cause unidirectional motion or uphill pumping of a substance. Our analysis
      suggests that molecular pumps such as Na,K-ATPase and molecular motors such as
      kinesin and myosin may share a common underlying mechanism.

PMID- 9760730
TI  - Limited flexibility of the inter-protofilament bonds in microtubules assembled
      from pure tubulin.
AB  - The superposition of the regular arrangement of tubulin subunits in microtubules
      gives rise to moire patterns in cryo-electron micrographs. The moire period can
      be predicted from the dimensions of the tubulin subunits and their arrangement in
      the surface lattice. Although the average experimental moire period is usually in
      good agreement with the theoretical one, there is variation both within and
      between microtubules. In this study, we addressed the origin of this variability.
      We examined different possibilities, including artefacts induced by the
      preparation of the vitrified samples, and variations of the parameters that
      describe the microtubule surface lattice. We show that neither flattening nor
      bending of the microtubules, nor changes in the subunit dimensions, can account
      for the moire period variations observed in 12 and 14 protofilament microtubules.
      These can be interpreted as slight variations, in the range -0.5 A to +0.9 A, of
      the lateral interactions between tubulin subunits in adjacent protofilaments.
      These results indicate that the inter-protofilament bonds are precisely
      maintained in microtubules assembled in vitro from pure tubulin. The fact that
      the moire period is not affected by bending indicates that the local interactions
      between tubulin subunits are sufficiently stiff to accommodate large deformations
      of the microtubule wall.

PMID- 9760731
TI  - Modeling elastic properties of microtubule tips and walls.
AB  - Electron micrographs of tips of growing and shrinking microtubules are analyzed
      and interpreted. The many shapes observed are all consistent with a simple
      mechanical model, a flexible tube with competing intrinsic curvatures.
      Observations are also consistent with growing and shrinking microtubules having
      the same intrinsic curvature for protofilaments, the one observed in oligomers
      peeling off shrinking microtubules. If this is so, the lateral bonds between
      protofilaments are responsible for the difference between shapes of tips on
      growing and shrinking microtubules.

PMID- 9760732
TI  - Diffusion inside microtubules.
AB  - Recent high-resolution analysis of tubulin's structure has led to the prediction
      that the taxol binding site and a tubulin acetylation site are on the interior of
      microtubules, suggesting that diffusion inside microtubules is potentially a
      biologically and clinically important process. To assess the rates of transport
      inside microtubules, predictions of diffusion time scales and concentration
      profiles were made using a model for diffusion with parameters estimated from
      experiments reported in the literature. Three specific cases were considered: 1)
      diffusion of alpha beta-tubulin dimer, 2) diffusion/binding of taxol, and 3)
      diffusion/binding of an antibody specific for an epitope on the microtubule's
      interior surface. In the first case tubulin is predicted to require only
      approximately 1 min to reach half the equilibrium concentration in the center of
      a 40 microns microtubule open at both ends. This relatively rapid transport
      occurs because of a lack of appreciable affinity between tubulin and the
      microtubule inner surface and occurs in spite of a three-fold reduction in
      diffusivity due to hindrance. By contrast the transport of taxol is much slower,
      requiring days (at nM concentrations) to reach half the equilibrium concentration
      in the center of a 40 microns microtubule having both ends open. This slow
      transport is the result of fast, reversible taxol binding to the microtubule's
      interior surface and the large capacity for taxol (approximately 12 mM based on
      interior volume of the microtubule). An antibody directed toward an epitope in
      the microtubule's interior is predicted to require years to approach equilibrium.
      These results are difficult to reconcile with previous experimental results where
      substantial taxol and antibody binding is achieved in minutes, suggesting that
      these binding sites are on the microtubule exterior. The slow transport rates
      also suggest that microtubules might be able to serve as vehicles for controlled
      release of drugs.

PMID- 9760733
TI  - A mathematical approach to cytoskeletal assembly.
AB  - The cytoskeleton is a fundamental and important part of cell's structure, and is
      known to play a large role in controlling the shape, function, division, and
      motility of the cell. In recent years, the traditional biological and biophysical
      experimental work on the cytoskeleton has been enhanced by a variety of
      theoretical, physical and mathematical approaches. Many of these approaches have
      been developed in the traditional frameworks of physicochemical and statistical
      mechanics or equilibrium thermodynamic principles. An alternative is to use
      kinetic modelling and couch the analysis in terms of differential equations which
      describe mean field properties of cytoskeletal networks or assemblies. This paper
      describes two such recent efforts. In the first part of the paper, a summary of
      work on the kinetics of polymerization, fragmentation, and dynamics of actin and
      polymers in the presence of gelsolin (which nulceates, fragments, and caps the
      filaments) is given. In the second part, some of the kinetic models aimed at
      elucidating the spatio-angular density distribution of actin filaments
      interacting via crosslinks is described. This model given insight into effects
      that govern the formation of clusters and bundles of actin filaments, and their
      spatial distribution.

PMID- 9760734
TI  - A computational model of ameboid deformation and locomotion.
AB  - Traditional continuum models of ameboid deformation and locomotion are limited by
      the computational difficulties intrinsic in free boundary conditions. A new model
      using the immersed boundary method overcomes these difficulties by representing
      the cell as a force field immersed in fluid domain. The forces can be derived
      from a direct mechanical interpretation of such cell components as the cell
      membrane, the actin cortex, and the transmembrane adhesions between the
      cytoskeleton and the substratum. The numerical cytoskeleton, modeled as a dynamic
      network of immersed springs, is able to qualitatively model the passive
      mechanical behavior of a shear-thinning viscoelastic fluid (Bottino 1997). The
      same network is used to generate active protrusive and contractile forces. When
      coordinated with the attachment-detachment cycle of the cell's adhesions to the
      substratum, these forces produce directed locomotion of the model ameba. With
      this model it is possible to study the effects of altering the numerical
      parameters upon the motility of the model cell in a manner suggestive of genetic
      deletion experiments. In the context of this ameboid cell model and its numerical
      implementation, simulations involving multicellular interaction, detailed
      internal signaling, and complex substrate geometries are tractable.

PMID- 9760735
TI  - Reliability of file-based retrospective ratings of psychopathy with the PCL-R.
AB  - A rapidly emerging consensus recognizes Hare's Psychopathy Checklist-Revised (PCL
      R; Hare, 1991) as the most valid and useful instrument to assess psychopathy
      (Fulero, 1995; Stone, 1995). We compared independent clinical PCL-R ratings of 40
      forensic adult male criminal offenders to retrospective file-only ratings. File
      based PCL-R ratings, in comparison to the clinical ratings, yielded categorical
      psychopathy diagnoses with a sensitivity of .57 and a specificity of .96. The
      intraclass correlation (ICC) of the total scores as estimated by ICC(2,1) was
      .88, and was markedly better on Factor 2, ICC(2,1) = .89, than on Factor 1,
      ICC(2,1) = .69. The findings support the belief that for research purposes, file
      only PCL-R ratings based on Swedish forensic psychiatric investigation records
      can be made with good alternate-form reliability.

PMID- 9760736
TI  - Assessment of adherence with multiple informants in pre-adolescents with spina
      bifida: initial development of a multidimensional, multitask parent-report
      questionnaire.
AB  - Adherence to medical regimens was assessed in 67 pre-adolescents with spina
      bifida (8- and 9-year-olds; 37 boys, 30 girls), with mother, father, teacher, and
      health professional report. The Parent-Report of Medical Adherence in Spina
      Bifida Scale (PROMASB) was developed and includes multidimensional scales for the
      following tasks: catheterization, bowel care, skin care, medication, and
      ambulation. With few exceptions, the PROMASB has adequate psychometric
      properties. However, findings revealed modest to low correlations between
      respondents. Mothers and fathers reported significantly more noncompliance than
      teachers and health professionals. For the most part, all informants reported
      that most children were compliant across all tasks. Additional analyses based on
      qualitative data suggest that parents attribute compliance difficulties to
      motivational as well as attentional-memory factors.

PMID- 9760737
TI  - The impact of "managed care" on the practice of psychological testing:
      preliminary findings.
AB  - Although the impact of managed care constraints on assessment practices has
      received recent attention, a review of the literature found no data-based
      articles that address this issue. We report survey data on 137 members of the
      National Register of Health Service Providers in Psychology (Council for the
      National Register of Health Service Providers in Psychology, 1996) on current
      testing practices. The majority (72%) reported that their use of tests has
      changed in the last 5 years due to managed care directives. These clinicians are
      doing less testing overall and restrict their pool of assessment instruments. The
      Rorschach inkblot technique (Rorschach, 1942), the Thematic Apperception Test
      (Murray, 1943), and the Wechsler Intelligence scales (Matarazzo, 1972) were the
      instruments most noted for disuse. Apparently, practitioners are relying more on
      short, brief self-report measures that tap targeted symptoms or problem areas,
      and less on tests that demand considerable clinicians' time. Implications and
      limitations of the findings are discussed.

PMID- 9760738
TI  - Identifying psychological contributions to chronic pain complaints with the MMPI
      2: the role of the K scale.
AB  - Although the 1-3/3-1 Minnesota Multiphasic Personality Inventory (MMPI) code type
      is traditionally interpreted as suggesting that somatic complaints are caused or
      exacerbated by psychological factors, prior research has raised questions about
      the validity of this interpretation for chronic pain patients. This study
      examined alternative strategies for using the MMPI to identify psychological
      contributions to chronic pain complaints. A sample of 125 chronic pain patients
      completed the MMPI-2. They were also rated by clinical staff on a set of
      descriptive statements reflecting psychological features that can contribute to
      physical complaints. MMPI patterns that are traditionally used to identify these
      features, such as the 1-3/3-1 code type, were not related to the ratings. A
      relation was found between scores on the K scale and the ratings, where patients
      with higher scores on the K scale (T > or = 56) received ratings suggesting less
      of a psychological contribution to their pain complaints. The implications of the
      findings for understanding the nature of the K scale are discussed.

PMID- 9760739
TI  - Further validation for the Cramer Defense Mechanism Manual.
AB  - This article presents psychometric properties of the Cramer Defense Mechanism
      Manual (Cramer, 1991b) for the Thematic Apperception Test (Murray, 1943). The
      developmental hierarchy of defenses originally postulated by Cramer was supported
      in this cross-sectional sample. Gender differences and the validity of
      distinguishing between "mature" and "immature" levels of defense were also
      investigated. Findings for gender differences largely replicate those previously
      reported by Cramer (1987, 1991a). Results also support the view of a
      developmental hierarchy of defenses and the validity of distinguishing between
      mature and immature levels of two of the three types of defenses.

PMID- 9760740
TI  - Childhood celebrity, parental attachment, and adult adjustment: the young
      performers study.
AB  - The associations between celebrity, parental attachment, and adult adjustment
      were examined among 74 famous, former young performers in television and film. As
      adults, former young performers whose parents served as their professional
      managers viewed their mothers as less caring and more overcontrolling than did
      performers whose parents were not their managers. Other factors affecting the
      quality of the parent-child relationship included dissatisfaction with money
      management, poor peer support, the perception that involvement in acting was
      determined by others, and the specific nature of professional experience.
      Together, these variables accounted for 59% of the variance in perceived caring
      and 40% of the variance in perceived autonomy support. The relation could not be
      attributed to a generalized response bias, as attachment was unrelated to degree
      of positive thinking. A Celebrity x Parental Attachment interaction indicated
      that the quality of the parent-child relationship moderated the effects of
      celebrity on adult adjustment: Among participants with good parental attachment,
      there was no relation between professional experience and adjustment; however,
      among participants with poor attachment, this relation was strong. Possible
      implications for parenting child actors and analogous populations of talented
      children in high-stress arenas are discussed.

PMID- 9760741
TI  - The Rorschach Schizophrenia Index (SCZI): an examination of reliability,
      validity, and diagnostic efficiency.
AB  - In this study, we investigate the reliability, validity, and diagnostic
      efficiency of the Rorschach Schizophrenia Index (SCZI) in relation to the
      accurate identification of patients diagnosed with Diagnostic and Statistical
      Manual of Mental Disorders (4th ed. [DSM-IV], American Psychiatric Association,
      1994) schizophrenia or other psychotic disorder (PD) according to the
      methodological recommendations offered by Wood, Nezworski, and Stejskal (1996).
      Seventy-eight patients who were found to meet DSM-IV criteria for a PD or Axis II
      disorder (PD = 33; borderline personality disorder = 23; Cluster A personality
      disorders = 9; Cluster C personality disorders = 13) and 50 nonclinical
      participants were compared on the SCZI. The results of this study indicate that
      the SCZI is internally consistent and can be reliably scored. In addition, the
      SCZI was used effectively in differentiating PD patients from patients with an
      Axis II disorder and from the participants in the nonclinical sample. Also, the
      SCZI variable was found to be empirically related to the presence of a DSM-IV
      diagnosis of PD. Finally, this variable could be employed for classification
      purposes in ways that were clinically meaningful in the diagnosis of a PD.
      Conceptual and methodological issues are discussed in relation to the assessment
      of psychosis.

PMID- 9760742
TI  - Cognitive and affective representations of people and MCMI-II personality
      psychopathology.
AB  - Hibbard, Hilsenroth, Hibbard, and Nash (1995) found that affective, but not
      cognitive, dimensions of object representations were related to the severity of
      psychopathology among outpatients. In this study, the Social Cognition and Object
      Relations Scale (Western, Barends, Leigh, Mendel, & Silbert, 1990) developed for
      interview data (Relationship Episodes; Luborsky, 1990) was used to assess the
      object representations of 33 men and 38 women entering psychotherapy. The Millon
      Clinical Multiaxial Inventory-II was used to assess the personality traits of the
      71 participants. The results support earlier findings that only affective
      dimensions of object representations are related to outpatient personality
      pathology.

PMID- 9760743
TI  - A new perspective on gender orientation measurement with the MMPI-2: development
      of the Masculine-Feminine Pathology Scale.
AB  - A new scale of gender orientation for the MMPI-2 (Minnesota Multiphasic
      Personality Inventory-II; Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989)
      called the Masculine-Feminine Pathology Scale, or Mfp, was developed as an
      alternative to the available Mf, GM, and GF scales. It differs from previous
      scales in its emphasis on symptomatic correlates of gender. Items were included
      in the new scale if they (a) discriminated between male and female psychiatric
      patients and (b) were likely to be indicators of psychopathology. Statistical
      analyses suggested an acceptably reliable but factorially complex scale. When
      used to predict clinician ratings of global psychopathology, the scale
      demonstrated incremental validity over both the existing gender-related scales
      and the traditional clinical scales. Scores at the "feminine" end of the Mfp
      scale seem to reflect distress characterized by high levels of anxiety. Scores at
      the "masculine" end of the Mfp scale suggest a more composed interpersonal
      presentation, which may reflect an amoral attitude. It is suggested that the new
      scale may prove superior to the existing gender role scales as a supplement to
      other clinical scales. Avenues for future research with the Mfp scale are
      discussed.

PMID- 9760744
TI  - Self-concept in children: equivalence of measurement and structure across gender
      and grade of Harter's Self-Perception Profile for Children.
AB  - In this study, we tested a Dutch version of Harter's (1985) Self-Perception
      Profile for Children for equivalence of measurement and structure across gender
      and age (grade), using the LISREL confirmatory factor analytic model. The sample
      consisted of 758 Flemish 4th, 5th, and 6th graders (8-13 years old, M = 10.5
      years old). Support was found for equivalence of structure for boys and girls,
      for 4th and 5th graders, and for 5th and 6th graders. Equivalence of measurement
      was only partially found. The relation between items and factors was invariant
      across gender and grade. The error of measurement however was not equivalent,
      indicating that the items had not the same reliability for boys and girls and
      across all grade groups.

PMID- 9760746
TI  - Influence of temperature, pH and water activity on "in vitro" inhibition of
      Penicillium glabrum (Wehmer) Westling by yeasts.
AB  - Four different yeast species (Metschnikowia pulcherrima, Saccharomycopsis vini,
      Kluyveromyces marxianus, Cryptococcus albidus), isolated from surface of grapes,
      were evaluated for biocontrol potential against Penicillium glabrum. In order to
      investigate the influence of temperature, pH, water activity and yeast cell
      concentration on Penicillium glabrum inhibition, the individual effects and the
      interaction of these factors were analyzed by means of a Central Composite Design
      (CCD). All yeast species tested showed antagonistic effects which were more
      pronounced at high cell concentrations. The other variables affected the
      antagonistic effect differentially depending on the yeast species. Results of the
      experimental design showed that the selective success of a competitive microflora
      is under environmental control; moreover, when microbial cells are subjected to
      multiple factors, the effects and the reciprocal interactions of the individual
      variables cannot be independently evaluated.

PMID- 9760747
TI  - Hansenula anomala as spoilage agent of cream-filled cakes.
AB  - The aims of this work were to identify the causal agents of the sporadic off
      odour occurrence in Italian cream-filled cakes and to investigate the yeasts
      associated to various ingredients as well as the final products. In the overall
      production of the considered confectionery, the phenomenon was linked to a
      specific type of filled-cake such as the one having the hazel nut pastry as an
      ingredient. This ingredient as well as the final products were characterized by
      high frequencies of the spoilage yeast Hansenula anomala. This species, due to
      attributes such as osmotolerance and the ability to produce high concentration of
      ethyl acetate, could exercise a decisive role in the occurrence of the off
      flavour.

PMID- 9760749
TI  - Purification and characterization of four catechol 1,2-dioxygenase isozymes from
      the benzamide-assimilating bacterium Arthrobacter species BA-5-17.
AB  - When Arthrobacter sp. BA-5-17 was grown on benzamide, the bacterium synthesized
      four different catechol 1,2-dioxygenase (CD, EC 1.13.11.1) isozymes (CD-I, II,
      III-1, and III-2). We purified each CD to homogeneity by a series of column
      chromatography. The molecular masses of the four CDs were between 68 and 72 kDa.
      The enzymes were made up of two identical subunits each with the molecular mass
      of 33 kDa. CD-I and II were indistinguishable in enzymatic properties tested.
      Most properties of CD-III-1 were similar to those of CD-III-2. However, CD-III-1
      had a marked adsorption peak at 325 nm, which disappeared in CD-III-2 as well as
      in CD-I and II. CD-III-1 and III-2 were much more resistant to heating and
      inhibitors than CD-I and II.

PMID- 9760750
TI  - The low level expression of chloramphenicol acetyltransferase (CAT) mRNA in
      Escherichia coli is not dependent on either Shine-Dalgarno or the downstream
      boxes in the CAT gene.
AB  - Recent studies have shown that the canonical Shine-Dalgarno (SD)-anti-SD
      interaction is dispensable for the initiation of translation of certain mRNAs in
      Escherichia coli. Alternative non-SD sequences (located upstream from the
      initiation codon) and also downstream sequences ("downstream boxes")
      complementary to 16S rRNA were found to be involved in the initiation of
      translation of mRNAs devoid of either SD or any leader sequences. In this study
      the chloramphenicol acetyltransferase (CAT) gene was modified to remove the 5'
      terminal non-translated region and/or the two potential downstream boxes in the
      CAT gene. Thus a series of ten CAT gene constructs was created and expressed in
      E. coli under a strong constitutive promoter. The results showed that CAT mRNAs
      devoid of both leader sequence nucleotides and the two downstream boxes in the
      CAT gene remained active in vivo and produced CAT protein in sufficient amounts
      for survival of the transformed cells at chloramphenicol concentrations up to 20
      30 micrograms/ml.

PMID- 9760751
TI  - Polyamine metabolism in Saccharomyces cerevisiae exposed to ethanol.
AB  - Growth of the yeast Saccharomyces cerevisiae was unaffected by up to 24 h
      exposure to ethanol concentrations ranging from 1% to 9%, but was reduced
      following exposure to 12% ethanol. Concentrations of the polyamines putrescine,
      cadaverine and spermidine were not affected by a 24 h exposure to 12% ethanol,
      although there was a significant increase in spermine level. These changes were
      accompanied by significant increases in the activities of the polyamine
      biosynthetic enzymes ornithine decarboxylase (ODC) and S-adenosylmethionine
      decarboxylase (AdoMetDC) and in the flux of label from ornithine into the
      polyamines. Formation of the cadaverine derivatives aminopropylcadaverine and N,N
      bis(3-aminopropyl)cadaverine was greatly increased in yeast exposed to 12%
      ethanol for 24 h, probably via the action of ODC, AdoMetDC and the
      aminopropyltransferases. Exposure to 12% ethanol also led to substantial
      reductions in the uptake of putrescine and spermidine and the amino acid
      methionine.

PMID- 9760752
TI  - [Workshop meeting of the German Pharmaceutical Society. 10-12 March 1997.
      Abstract].

PMID- 9760753
TI  - National Scientific Medical Meeting. 27-28 March 1998. Abstracts.

PMID- 9760754
TI  - [XV National Congress of the Spanish Society of Parenteral and Enteral Nutrition.
      Alicante, 13-15 May 1998. Abstracts].

PMID- 9760755
TI  - [6th Congress of the Union of Swiss Surgical Societies. Lausanne, Switzerland, 24
      27 June 1998. Abstracts].

PMID- 9760756
TI  - 1998 Receptor and ion channel nomenclature.

PMID- 9760757
TI  - [Another look at the AIDS virus].

PMID- 9760758
TI  - [Therapeutic approach to acute myeloid leukemia].
AB  - The treatment of acute myeloid leukemia has evolved considerably over the past
      decade. While induction therapy appears to have been almost standardized, there
      continues to be an ongoing debate and controversy regarding the best form of post
      remission therapy. Attempts are being made to identify patients at particular
      risk of relapse to enable appropriate selection of best induction and post
      remission therapies. In these respects, cytogenetics are useful. New concepts
      include the use of growth factors, immunotherapy, MDR modulation and therapies
      evolving from a better knowledge of the anomalies of the genes that cause
      leukemia.

PMID- 9760759
TI  - [Intestinal transplantation: a clinical reality in 1998].
AB  - Each year, thousands of peoples die, suffering from an anatomical or functional
      loss of their intestine; these patients would benefit from bowel transplantation;
      the difficulties of bowel transplantation are as follows: 1. the physiological
      characteristics of the small bowel, and the fact that denervation, lymphatics
      interruption and ischemia, independently from rejection, may disturb its
      function; 2. secondly, the organ is septic; thus, its transplantation causes
      major infectious problems; 3. at last, the immunological characteristics of the
      intestinal allograft. Bowel transplantation causes a two-way immunological
      conflict, not only a standard rejection response, but also a graft-versus-host
      disease, similar to that observed after bone marrow transplantation; this
      reaction is caused by the lymphoid tissue conveyed within the bowel graft. The
      introduction of a new immunosuppressive molecule, FK 506, in combination with
      profound antibiotic prophylactic regimens, decontamination protocols and vigorous
      anti-viral protection (against cytomegalovirus and Epstein-Barr), have
      significantly improved the results. Bowel transplantation has recently reached
      clinical application. The one-year survival rate of intestinal grafts reaches now
      70%. Still, there is no doubt that, due to its microbiological and immunological
      characteristics, the small bowel will remain the most challenging abdominal organ
      to transplant.

PMID- 9760761
TI  - [Evidence of new diagnostic and prognostic human astrocytoma tumor markers.
      Potential therapeutic applications. I].
AB  - This paper summarises different studies of our group whose aim to improve the
      accuracy of prognostic values for patients with astrocytic tumors. Our approach
      aims to optimise the conventional evaluation of astrocytic tumor malignancy by
      means of the quantification of conventional morphological criteria, and the
      production of biological variables related to DNA ploidy level. All these
      quantitative variables have been generated by means of computer-assisted
      microscopy and submitted to adapted data analysis methods. A series of 250
      astrocytic tumors has been analysed, including 39 astrocytomas (AST), 47
      anaplastic astrocytomas (ANA) and 164 glioblastomas (GBM) identified in
      accordance with the WHO classification. This classification distinguishes between
      tumor groups with relatively (AST), intermediary (ANA) and unfavorable (GBM)
      prognoses. However, it does not take into account the high degree of
      heterogeneity in each tumor group and may thus be poorly for individual case
      prediction. In this context, our approach has been able to identify new entities
      in the AST and ANA histological groups. These entities have established some
      reference points on the biological continuum according to the sequence AST-->ANA-
      >GBM and enable prognosis evaluation to be improved in astrocytic tumors.

PMID- 9760762
TI  - [Evidence of new diagnostic and prognostic human astrocytoma tumor markers.
      Potential therapeutic applications. II].
AB  - Human astrocytic tumors grow into the normal brain parenchyma either as localized
      tumors, or as highly diffuse neoplasms. The diffuse phenotype relates to a
      specific sub-type of neoplastic astrocytes with a high motility and invasion
      capacity. Motility features refer to locomotion while invasion features refer to
      protease secretion. Our data reveal that several peptides belonging to the
      gastrin/cholecystokinin peptide class are able to significantly (and in certain
      cases very significantly) modify the level of tumor growth (at the level of cell
      proliferation and/or cell death), of motility and of invasion in various
      experimental models of human astrocytic tumors. We are synthesizing various
      gastrin/cholecystokinin-related peptides in order to develop clinical
      applications with which we want to inhibit astrocytic tumor growth, individual
      neoplastic astrocytic motility and the invasion of the normal brain parenchyma.

PMID- 9760763
TI  - [Chromosome sensitivity to bleomycin-induced damage in patients with laryngeal
      cancer as a marker of genetic risk].
AB  - An inter-individual variability in sensitivity to mutagen-induced genotoxicity
      was studied in respect to an estimation of larynx cancer risk. Bleomycin induced
      chromosome breaks were analysed in blood lymphocytes proliferating in vitro in a
      group of 35 larynx cancer subjects and in 18 healthy controls. A significantly
      higher index of chromosome breaks was found in larynx cancer subjects as compared
      with the controls. The distribution of individual results indicates that subjects
      oversensitive to bleomycine were identified only among laryngeal tumour patients.
      A potential usage of bleomycin test in tumour prognosis is discussed.

PMID- 9760764
TI  - [Surgical treatment of hypopharyngeal cancer: reconstructive methods].
AB  - The paper presents a 26-year experience of the ENT Clinic of the Pomeranian
      Medical Academy in Szczecin with 20 patients who underwent reconstruction of the
      hypopharynx after resection for locally advanced carcinoma. The procedures were
      carried out in years 1970-1995. The reconstructions included 7 musculomucosal
      pedicle flaps obtained from the base of the tongue, 5 epiglottis pedicle flaps, 4
      tubed pectoralis major musculocutaneous flaps, 1 vascular pedicle submandibular
      gland flap, 1 deltopectoral flap, 1 skin flap and 1 island pectoralis major
      musculocutaneous flap. An analysis of the procedures with emphasis on the
      oncological and functional results indicates that each techniques has advantages
      in specific circumstances. Guidelines for the application of the techniques are
      described.

PMID- 9760765
TI  - [The results of surgical treatment of patients with laryngeal carcinoma in years
      1988-1989 in four departments of otorhinolaryngology].
AB  - In a group of 579 patients with laryngeal carcinoma treated surgically in years
      1988-1989 in four departments of otorhinolaryngology of the Medical Academies in
      Poznan, Warsaw, Cracow and Lublin, 72% survived 3 years without recurrence and
      59% survived 5 years. Similar results were obtained in years 1986-1987. The
      authors discuss in detail the reasons for failures of the surgical treatment,
      i.e.: supraglottic localization of the cancer, its extensiveness in the larynx,
      the stage of clinical development, general condition of the patient,
      effectiveness of the operation, regularity of postsurgical examination, the
      degree of histological malignancy, blood transfusion during the operation,
      distant metastases, little efficiency of medical service in early diagnosis of
      laryngeal cancer, avoiding postsurgical radiation, subjective factors of the
      patients and the choice of the optimal method of the treatment. Few patients can
      be cured if the initial treatment fails.

PMID- 9760766
TI  - [On fronto-anterior reconstructive laryngectomy].
AB  - The paper describes improved fronto-anterior reconstructive laryngectomy using
      liberated specifically pediculated and lowered glottis to replace the removed
      anterior segment of the thyroid cartilage. The very technique as well as its
      advantages are discussed. The main advantage of the method is that it makes use
      of the pediculates, well vasculated glottal cartilage covered with cilliar
      epithelium preserving the physiological direction of the cilliar movement. The
      cartillage is significantly thicker than the free nasal septum cartilage
      transplant used until recently. Post-operative discomfort is manifested by
      temporary difficulties in swallowing connected with the covered glottis. The
      procedure is technically uncomplicated, the vasculated cartilage heals very well
      and the respiratory and phoniatric effects are satisfactory.

PMID- 9760767
TI  - [Therapeutic effectiveness of Cedax in the treatment of selected acute upper
      respiratory diseases].
AB  - A group of 66 patients with acute inflammatory upper respiratory tract diseases
      were examined in the ENT Department of Poznan Medical Academy between November
      1996 and November 1997. Specimens for bacteriological cultures were collected
      from the ear, nose and throat. The subjects were treated with ceftibuten.
      Clinical improvement was reported in all cases. In 44 patients, ceftibuten
      treatment eliminated pathogenic bacteria (as evidenced by microbiological
      analysis).

PMID- 9760768
TI  - [The role of imperfect fungi in etiopathogenesis of allergic rhinitis].
AB  - In this paper the role of imperfect fungi in etiopathogenesis of perennial
      rhinitis was examined. In a group of 26 patients the concentration of total IgE
      and IgE specific of Candida albicans, Aspergillus fumigatus, Alternaria
      alternata, Mucor racemosus and Cladosporum herbarum was signified.
      Oversensibility to imperfect fungi was confirmed in 30.8% of patients: to Candida
      albicans in 3.8%, to Aspergillus fumigatus in 11.5%, to Alternaria alternata in
      3.8%, to Mucor racemosus in 7.6% and to Cladosporum herbarum in 3.8%.

PMID- 9760769
TI  - [Efficiency evaluation of radiotherapy of recurrences after surgery in head and
      neck cancer].
AB  - An analysis of 200 consecutive patients with head and neck squamous cell cancer
      treated after surgery with radiation at the Centre of Oncology, Maria Sklodowska
      Curie Memorial Institute in Gliwice was performed. At the beginning of
      radiotherapy recurrences were found in 67 (33.5%) patients. Recurrences were
      diagnosed at the primary site exclusively in 30 patients, in lymph nodes only in
      21 patients, in both localizations in 14 patients, and in 2 patients in the
      tracheostomy. Conventional 60Co radiation treatment to the mean total dose of
      62.5 Gy was applied. Three year disease-free survival probability was 22% for
      patients with recurrences comparing to 54% for patients with no relapse. In the
      group of patients with recurrences better prognosis was found for patients with
      preoperatively early stages, and with early recurrences, located in the primary
      tumour site, which completely responded to radiotherapy. High rate of recurrences
      after surgery for head and neck cancer and low probability of recurrence control
      with radiotherapy indicate the necessity of more careful qualification for
      surgical treatment.

PMID- 9760770
TI  - [Correlations between topography of the main structures of the temporal bone and
      the location of the sigmoid sinus].
AB  - Topographical relations between main structures of the temporal bone are
      important for otosurgeons. There were reports aiming at establishing some laws in
      the temporal bone building, that would allow to anticipate the location of the
      important structures in the temporal bone. It is obvious nowadays that precise
      and absolute rules do not exist. In the present study the aim was to estimate if
      there are statistically significant correlations between some dimensional
      parameters of the temporal bone. It was stated that the smaller the distance
      between the sigmoid sinus and the external auditory meatus, the higher the
      jugular bulb is situated. Coefficient in this correlation was 0.46. However, no
      correlation was found between the location of the sigmoid sinus and the facial
      nerve on one hand and the internal carotid artery on the other. It is important
      for otosurgeons to know that the prominent sigmoid sinus does not determine
      existence of a narrow facial recess.

PMID- 9760771
TI  - [Histological and histochemical investigation of pathological laryngeal mucosa
      with papillomatosis in children and adults].
AB  - Papillomas of the larynx are the subject of numerous studies. They occur in two
      forms (multiple and singular). The authors presented the results of histological
      and histochemical investigations of larynx papillomas in 9 adults and 16
      children. The studies comprised patients treated in the Clinic of Otolaryngology
      in Wroclaw. Surgically removed lesions constituted the material for estimation.
      Peculiar attention was paid to the degree of differentiation of tumours under the
      microscope. The interdependence between intensification of reaction and degree of
      epithelhyperplasia and strict connection of intensification of reaction with
      quantity of dysplastic changes of epithelium were indicated by estimation of
      enzymatic reactions. Histological studies disclosed marked morphological
      differences between papillomas in children and adults. The correlation of
      reactions to lactic dehydrogenase and NADH2-tetrazole reductase can be treated as
      an expression of hyperplastic changes in the epithelium. What is more, the
      reaction to lactic dehydrogenase may be regarded as a metabolic index of
      malignancy.

PMID- 9760772
TI  - [The role of human papillomavirus (HPV) infection in the pathogenesis of the
      laryngeal cancer].
AB  - In the paper the role of virus infection in carcinogenesis was presented.
      Particular significance of human papillomavirus infection in the neoplastic
      diseases, also in the laryngeal cancer was emphasized.

PMID- 9760773
TI  - [Issues in total reconstruction of the auricle in microtia].
AB  - The author's personal experience with 83 cases of auricular construction is
      presented, as well as methods that have evolved through the last 3 decades. The
      details of reconstructive procedure are discussed. Advisability of external ear
      reconstruction in unilateral microtia is evaluated. The follow-up ranges from 2
      to over 20 years. Major complications occurred in only 3% of cases and were
      limited to the perioperative period. The significance of the emotional and
      psychological benefits of the operation is emphasized. Photographic evidence is
      presented, too.

PMID- 9760774
TI  - [The use of the ox's vein for myringotomy of the ear].
AB  - The study presents a modification of the method developed by Zini et al. to
      prepare an ox's vein for a myringoplasty. The graft of the vein was pickled in a
      trypsin solution, fixed in formaldehyde and stored in a 70% ethanol solution. It
      was established that the incubation period of the vein in the trypsin solution
      required to produce the best histological specimens for this purpose was 5 hours.
      The preparation of the ox vein for a graft with the use of trypsin is relatively
      simple and inexpensive. Xenografts of ox veins for use in myringoplasties in
      humans are a good material and may be successfully used both in reconstructions
      of large defects in the tympanic membrane and in operations to correct congenital
      atresia of the ear.

PMID- 9760775
TI  - [Diagnostic problems in coexistence of paranasal sinusitis with cerebral tumor].
AB  - Differential diagnosis between the intracranial complications of paranasal
      sinusitis and cerebral tumor belongs to very difficult tasks in otolaryngology
      and neurosurgery. Complications of sinusitis, such as intracranial abscess
      formation, are uncommon and often clinically unremarkable. The arising
      difficulties are even greater in inflammatory intracranial complications of
      sinusitis, giving symptoms similar to those of cerebral tumors. The illustrative
      case report was presented.

PMID- 9760776
TI  - [Mast cells in eosinophilic and neutrophilic nasal polyps. Cytological and
      histological examinations].
AB  - In 10 patients with nasal polyps mast cells were counted in smears and in polyp
      tissues. In smears from neutrophilic polyps (n = 4) no mast cells were found, in
      eosynophilic polyps (n = 6) mast cells were found on an average of 7.5%.
      Histological examinations showed that an average number of mast cells in the
      connective tissue was similar in both types of polyps. In the epithelial layer of
      neutrophilic polyps the number of mast cells was slightly greater than in
      eosynophilic polyps. In an atopic patient the number was 12 times greater than in
      the other cases. No dependence was found between the number of mast cells in
      smears and in the tissue.

PMID- 9760777
TI  - [Acoustic rhinometry in the assessment of the topical treatment of upper
      respiratory infections with fusafungin].
AB  - The aim of the study was to estimate by means of acoustic rhinometry (AR) the
      nasal blockade in 37 patients (5-73 years old, mean 32) with upper airways
      infections treated by fusafungine. The examinations were carried out on the first
      (D1) and seventh day (D7) of observation. Cross-sectional area (CA) mean values
      of 3 cm sector laid back to C notch of AR curves (CA-C3) were selected to the
      analysis. RESULTS: The mean value of CA-C3: in all patients it was 2.61 cm2 on D1
      and 2.8 cm2 on D7; in rhinitis and sinusitis patients--2.23 cm2, in others--3.16
      cm2; without nasal discharge--3.48 cm2, in others (with severe or medium)--2.53
      cm2 and 2.48 cm2 respectively. 29 patients had nasal blockade (78.4%) with mean
      CA-C3 = 2.34 cm2 (others--3.56, p < 0.05). During seven days the following
      enlargement of CA-C3 was reported: 14.9% in all patients (p < 0.01); in viral
      infections 24% (n = 14, p < 0.01), bacterial 14.3% (n = 11, NI); in nasal
      blockade patients--15.22%, others--13.55% (p < 0.01). Mean value of CA-C3
      increased by 37.7% in patients who demonstrated, according to the physicians,
      "very good improvement", 5.7%--"good", 1.5%--"weak" (p < 0.05). There was also
      enlargement of nasal cavities in CA-C3 in non-sneezers (p < 0.05) and medium
      discharge symptom patients (p < 0.05). There was no statistical difference in
      clinical and acoustic rhinometry results between patients treated with
      fusafungine together with non-steroid anti-inflammatory drugs and patients
      treated with fusafungine. CONCLUSION: AR is a good instrument to be used in the
      objective assessment of the nasal blockade changes in people with infection of
      the nasal mucosa and showed positive efficacy of fusafungine in the treatment of
      upper airway infection.

PMID- 9760778
TI  - [On the frequency of Meniere's disease occurrence].
AB  - The authors estimated the frequency of Meniere's disease occurrence among
      patients of Department of Otolaryngology, University School of Medicine in Lodz
      in years 1986-1995. The incidence of Meniere's disease was evaluated as 0.46% of
      all clinic patients and as 1.7% of cases which were treated for aural diseases.
      Diagnosis was made on the basis of clinical symptomatology, exact medical
      examination and audiologic tests. The function of vestibular organs was assessed
      with the help of caloric tests with ENG recordings. Meniere's disease incidence
      has been the subject of many epidemiological papers in literature but the exact
      values are different. Perhaps it can be attributed to a variety of criteria
      applied in defining Meniere's disease or to epidemiological differences.

PMID- 9760779
TI  - [Juliusz Lempert (1890-1959): the author of the fenestration technique].
AB  - Juliusz Lempert was born in 1890 in Poland. A few years later the poor Jewish
      family emigrated to the United States. Lempert obtained his MD degree at Long
      Island Medical College, and soon after that established a small hospital of his
      own in Manhattan. Later he bought an old five-storey building and converted it
      into a new otological medical center, which he called Endaural Hospital. His life
      was rather difficult with the wave of antisemitism in the United States and the
      adversity which he encountered so many times. However his contribution to the
      microsurgical treatment of conductive deafness is immense. He elaborated and
      introduced a new method of mastoidectomy and, first of all, fenestration--a new
      one-stage surgical technique to be applied in cases of otosclerosis. This
      precise, sophisticated operation revolutionized surgical treatment. With a
      dentist's drill Lempert created a new window on the horizontal canal, in this way
      the sound wave could stimulate the inner ear. He was to call it "fenestration nov
      ovalis". Lempert was never a member of any ENT society and worked in his hospital
      alone. When suddenly his only son was stricken with leukemia and died, Lempert
      was completely broken, and never returned to this work. The next blows were new
      operative methods of otosclerosis: stapes mobilisation introduced by Rosen and
      stapedectomy by Shea. He never accepted these new techniques. It was a painful
      experience for a surgical genius who had at so many times been hurt during his
      life. He could not believe that his fenestration was definitely gone. Lempert
      quickly deteriorated physically and mentally, and died in 1958.

PMID- 9760780
TI  - [Voice function after chordectomy in patients with larynx carcinoma].
AB  - The quality of voice was examined in 18 patients with larynx carcinoma before and
      after chordectomy. Subjective and objective (spectrographic) methods were
      applied. The larynx was examined in indirect laryngoscopy and videostroboscopy.
      Significant voice pathology was found in patients before surgery when compared
      with norm. Early phoniatric rehabilitation helped to achieve subjective
      improvement of voice quality in patients after surgery.

PMID- 9760781
TI  - [A rare case of multiple primary malignant neoplasms of parotid gland:
      fibrosarcoma and squamous cell carcinoma].
AB  - Primary multiple malignant neoplasms and multifocal neoplasms are a very complex
      problem and therefore have been a topic of many articles. The mechanism of
      origin, frequency of occurrence, co-existence of neoplasms in functionally
      similar organs (uterus, mammary gland), heredity, a possibility of diagnostic and
      therapy are the most interesting aspects. Frequency of multiple primary malignant
      neoplasms occurrence is about 2-8% and still increases. Pathogenesis of
      multifocal and multiple neoplasms has rarely been a subject of articles. A
      simultaneous exposure of a tissue to damaging factors and special tissue
      sensitivity are the main reasons for neoplasms origin in this group. The authors
      present a rare case of parotid gland multiple neoplasm: fibrosarcoma and squamous
      cell carcinoma, as well as discuss the diagnostics, therapy, and prognosis of
      multiple neoplasms.

PMID- 9760782
TI  - [Myxoedema after radiotherapy of the laryngeal cancer].
AB  - In a 49-year-old woman carcinoma planoepithelialie akeratodes of the right vocal
      cord was diagnosed. The lesion was removed with the Kleinasser's microsurgery
      procedure. During telecobaltotherapy, temporary oedema of the face and the neck
      as well as dysphagia appeared. Myxoedema due to insufficiency of the thyroid was
      diagnosed after four months since the end of the radiotherapy. Substitutional
      treatment resulted in the hormonal and clinical improvement of the patient.

PMID- 9760783
TI  - [Selected etiological factors in the pathogenesis of subglottic laryngitis in
      children].

PMID- 9760784
TI  - [Evaluation of changes in the course of seasonal allergic nasal mucosa
      inflammation].

PMID- 9760785
TI  - [The rehabilitation program for the patients after cochlear implantation].

PMID- 9760786
TI  - [Respiratory tract symptoms in school children exposed to indoor and outdoor air
      pollution].
AB  - The epidemiologic study has been carried out in 1129 nine-year old schoolchildren
      in 4 city areas of Krakow, which differed in air pollution levels. Indoor air
      quality was assessed by the presence of the environmental tobacco smoke, type of
      domestic heating and the presence of molds or dampness on the walls. The
      occurrence of two or more respiratory symptoms (chronic cough, chronic phlegm,
      wheezing, dyspnea attacks, breathlessness or hay fever) was associated
      significantly with the outdoor air pollution score (chi 2 for trend = 13.315,
      df:1, p = .0000), with molds/dampness on the walls (OR = 2.16, 95% CI: 1.45-3.22)
      and allergy in children (OR = 5.94, 95% CI: 4.12-8.59). Since the results have
      shown the significant relationship between allergy and outdoor air pollution as
      well, the study confirms that outdoor pollutants increase the risk of allergic
      sensitization of young children.

PMID- 9760787
TI  - [Usefulness of cryoapplication for bleeding after needle biopsy during fiberoptic
      bronchoscopy].
AB  - The protective role of superficial freezing (using a "spray" N2O cryoprobe) of
      tracheobronchial tumours before fiberoptic biopsy was evaluated in 21 patients
      with suspected lung cancer and high risk of bleeding. An excellent haemostatic
      effect was observed in all but two patients despite 3-9 specimens taken into
      histopathological examination. No serious complications besides a transient cough
      in 5 patients were observed. So a new "spray" type cryoprobe was found useful in
      protection against bleeding during bronchoscopy without negative influence on the
      histopathological confirmation of malignancy.

PMID- 9760788
TI  - [Evaluation of angiogenic activity in sera from patients with interstitial lung
      diseases].
AB  - Angiogenesis is a process of new blood vessels' formation occurring in many
      physiological and pathological conditions. Neovascularisation is the principal
      vascular response in chronic inflammation and concomitant fibrotic process.
      Microvascular changes in various organ sites in sarcoidosis (BBS) and some of the
      symptoms of the disease may be related to microangiopathy. Moreover, vascular
      alterations were also observed in lung specimens from idiopathic pulmonary
      fibrosis (IPF) and avian fanciers lung (AFL) patients. The present study was
      aimed at testing the effects of serum from 43 patients with ILD (24 BBS, 8 AFL, 8
      IPF, 3 DIPF--drug induced pulmonary fibrosis) and 11 healthy controls on
      angiogenic capability of normal blood peripheral mononuclear cells (PBMC) in the
      murine intradermal angiogenesis assay (according to Sidky and Auerbach). The data
      demonstrated that sera from ILD patients significantly enhanced angiogenic
      capacity of normal PBMC as compared to control sera (p < 0.001). The effect was
      more pronounced for AFL patients than for BBS and IPF ones (p < 0.05). Sera from
      DIPF did not stimulate angiogenesis compared to control sera. The data showed
      that sera from ILD patients constitute sources of mediators participating in
      angiogenesis. This phenomenon may play role in pathogenesis of chronic
      immunological processes in lung.

PMID- 9760789
TI  - [Complications after BCG vaccination in the urban section of Lodz in the years
      1994-5].
AB  - The purpose of this paper was to evaluate the incidence of complications after
      BCG vaccination in children from urban area of Lodz in 1994-1995 and to give
      their pathological and prognostic interpretation on the basis of immunological
      and Groer allergometric examinations. The obtained data demonstrate that
      postvaccinal complications occurred in 46 children, that is 0.7/1000 of
      vaccinated population. They were observed mainly in newborns (45.7%), whereas
      they were particularly rare in revaccinated six-year-old children (13%) and
      schoolchildren (8.7%). In half of the cases there was an evidence of ulceration
      and suppuration in the site of vaccination, in another half--suppuration of local
      lymph nodes with or without fistula. Immunological and allergometric examinations
      were carried out in 21 children with post-vaccinal complications and 21 children
      with normal post-vaccinal period. In both groups the following were the subjects
      of evaluation: values of B and T lymphocytes and their CD4 and CD8
      subpopulations, lymphocytes proliferative response to mitogenic PHA doses and
      tuberculin, as well as IgG, IgA and IgM levels. Immunological and allergometric
      examinations indicated that immunosuppression was neither the cause nor the
      effect of BCG complications.

PMID- 9760790
TI  - [Staphylococcal pneumonia--analysis of material from patients treated at the
      Hospital for Lung Diseases in the years 1981-1994].
AB  - Retrospective analysis of staphylococcal pneumonia was made in 182 patients, aged
      18-88 years /61% more than 60 years old/ treated in hospital in years 1981-1994.
      Majority of these patients had various concomitant diseases, mostly chronic
      bronchitis and lung cancer. Strains of Staphylococcus aureus were sensitive
      mainly to amoxycillin--clavulanic acid, roxitromycin, amikacin, netilmicin,
      clindamycin, cefamandol, chloramphenicol, rifampicin and resistant mostly to
      penicillin /90% of strains/, ampicillin, tetracyclines. In many cases initial
      antibacterial treatment was inadequate in relation to sensitivity pattern of
      staphylococci--hence many changes of antibiotics were observed in the course of
      the therapy. Newer antistaphylococcal drugs were applied only in the last years
      of the study. Despite these therapeutical drawback outcome of staphylococcal
      pneumonia was good in 85% of patients; 14% of patients died /mainly as a
      consequence of comorbidities/. Successful therapy of staphylococcal pneumonia
      requires early recognition of possibility of infection due to Staphylococcus
      aureus and adjustment of drugs to probable or actual sensitivity of these
      pathogens.

PMID- 9760791
TI  - [The effect of nedocromil sodium on spontaneous production of histamine releasing
      factor (HRF) by mononuclear blood cells in patients with nonatopic bronchial
      asthma].
AB  - The aim of the study was to evaluate the effect of 28-days antiinflammatory
      treatment with nedocromil sodium (Ned.sod.) (Tilade-8 mg/24 hours) on nonspecific
      bronchial hyperreactivity (PC20H in mg/ml) and spontaneous HRF activity
      production by mononuclear blood cells in patients with nonatopic bronchial asthma
      treated with beclomethasone dipropionate. The correlation between PC20H and HRF
      was also examined. The study was performed in 10 subjects with mild and moderate
      chronic, stable asthma in a double-blind, placebo-controlled way. Placebo and
      Ned. sod were given through 4 weeks in a randomized way with 8 weeks wash-out
      period. It was shown that Ned. sod. did not influence clinical asthma symptom
      scores, ventilatory parameters and PC20H. No changes in the spontaneous
      production of HRF activity were observed. The correlation between HRF activity
      and PC20H assessed 4 times was not significant. The authors conclude that studies
      with Ned. sod. in nonatopic asthma should be continued, but the dosage of the
      drug ought to be bigger and the time of treatment should to be longer.

PMID- 9760792
TI  - [Clinical evaluation of side effects during immunotherapy with Catalet T in
      patients with hay fever].
AB  - The aim of this study was to evaluate the frequency of side effects during
      specific immunotherapy with Catalet T and to compare the frequency of side
      effects between different groups of patients according to time of immunotherapy
      continuation (from 1 to 5 years). The study was carried on 100 patients aged from
      12 to 58 years. The tolerance of Catalet was good. 83% of investigated patients
      finished the immunotherapy course with minimal or no side effects. The prevalence
      of side effects was the same independently from the time of immunotherapy.

PMID- 9760793
TI  - [Evaluation of the efficacy of nebulized salbutamol in exacerbation of chronic
      asthma].
AB  - The aim of the study was to evaluate the influence of nebulized salbutamol in low
      doses (0.5 mg, 1 mg, 1.5 mg) on lung function in patients with acute severe
      asthma. The study was performed in 30 patients--22 female and 8 male. Nebulized
      salbutamol proved to be an effective bronchodilating drug which enables to
      control exacerbations in asthmatic patients receiving conventional medical
      treatment. The evaluation of effect of nebulized salbutamol should take into
      account both subjective symptoms and (basic) spirometry parameters of airway
      obstruction such as FEV1 PEF. This therapy can improve the efficacy of asthma
      management.

PMID- 9760794
TI  - [Diagnostic difficulties with detection of foreign bodies from the lower
      respiratory tract--late detection].
AB  - Five cases of aspirated foreign bodies in bronchial tree were described. The
      clinical symptoms did not suggest the real cause of the illness and most of
      patients did not remember the fact of foreign body aspiration. The foreign bodies
      were removed during bronchofiberoscopy performed in local anaesthesia.

PMID- 9760795
TI  - [Estimation of the value of a self-designed questionnaire in diagnosing patients
      with suspected obstructive sleep apnea].
AB  - We have investigated the use of our own sleep questionnaire as a screening test
      for patients suspected of obstructive sleep apnoea (OSA). We examined 156
      unselected patients (mean age 49.5 +/- 0.9 years) referred to our clinic because
      of snoring or excessive daytime sleepiness. Each subject answered the
      questionnaire and underwent full standard polysomonography (PSG). Diagnosis of
      OSA, based on PSG, was established when AHI > 10. Significant correlations
      between AHI and questionnaire questions were found for BMI (r = 0.54, p < 0.001),
      questions considering snoring (r = 0.3, p < 0.001), questions considering apnoeas
      during sleep, difficulties with falling asleep and nycturia (r = 0.21, p < 0.01)
      and questions asking for dry mouth and tongue in the morning and excessive
      daytime sleepiness (r = 0.16, p < 0.05). Sensitivity and specificity of
      investigated questionnaire to confirm the disease were: 92% and 38%,
      respectively. Evaluated questionnaire helps to select patients with severe form
      of OSA demanding quick diagnosis and treatment.

PMID- 9760796
TI  - [Hepatic tuberculosis].
AB  - Tuberculosis of the liver can be the only manifestation of the disease or it may
      be a part of disseminated process. Three cases of liver tuberculosis were
      presented. In one of them the process was restricted to the liver and the
      diagnosis was made only at autopsy. In two other cases, tuberculosis of the liver
      was a part of disseminated process. In one of them the impairment of liver
      function improved after therapy and in another one, in spite of therapy, the
      patient died with signs of cardio-respiratory and hepatic insufficiency.

PMID- 9760797
TI  - [Chronic inflammatory changes in the lung of an 8-year old boy].
AB  - A case of pulmonary actinomycosis in the child is described. Firstly, tumor of
      lung was suspected. Correct diagnosis was made after thoracotomy and histological
      examination of material.

PMID- 9760798
TI  - [Evaluation of penetrating heart wounds by echocardiography].
AB  - The paper presents a rare case of a penetrating endocardial wound, managed
      conservatively, in which echocardiography was used in the serial monitoring.
      Heart injuries constitute about 6% of all chest injuries. Because of the
      possibility of cardiac tamponade and the massive bleeding into the pleural
      cavity, they are life-threatening. In such cases only surgical intervention gives
      a chance to save the patient (5). It turns out, however, that patients with
      normal echocardiogram and normal vital signs can be managed conservatively, with
      echocardiographic monitoring.

PMID- 9760799
TI  - [Disruption of the middle bronchus].
AB  - Disruption of the middle lobe broncus as a result of blunt chest trauma is
      described. Patient underwent emergency reconstructive operation. Follow-up
      examination revealed normal postoperative chest radiogram but bronchoscopy showed
      decreased patency of bronchial anastomosis. Perfusion lung scintigraphy showed
      severely decreased perfusion of the entire right lung. Concomitant fracture of
      right clavicle resulted in false joint which required surgical intervention 4
      weeks after the chest trauma.

PMID- 9760800
TI  - [Behcet's disease with pulmonary vessel involvement].
AB  - The case of systemic vasculitis with involvement of pulmonary vessels was
      described. 36-years white woman with cerebral vasculitis and recurrent uveitis 5
      and 3 years ago, now was admitted to hospital because of the mouth ulceration and
      lesions in the chest x-ray. After lung cancer exclusion, aneurysm of pulmonary
      artery branch was confirmed by dynamic tomocomputer examination All mentioned
      above manifestations were diagnosed as Behcet disease. Patient was treated with
      prednison, cyclophosphamide and cyclosporine. Clinical effect was observed after
      corticotherapy, but no improvement in chest X-ray picture was obtained also after
      immunosuppression. Patient died because of pulmonary haemorrhage 7 years after
      first symptoms of vasculitis and 2 years after first massive haemorrhage.

PMID- 9760801
TI  - [Pneumonia as a nosocomial infection].

PMID- 9760802
TI  - [Lung apex tumor].

PMID- 9760803
TI  - [Fibrinolytic treatment of pulmonary embolism].

PMID- 9760804
TI  - [The significance of scintigraphic, echocardiographic and electrocardiographic
      left atrial transesophageal pacing in diagnosis of ischemic heart disease].
AB  - The aim of the study was to compare the perfusion scintigraphy (using SPECT
      method with Tc-99-MIBI) during left atrial transoesophageal pacing test (LAPT)
      with pacing electrocardiography (ECG), echocardiography (ECHO) and
      electrocardiography exercise test (ExT) in ischaemic heart disease (IHD)
      diagnostics. The effect of LATP on heart haemodynamic parameters and the
      correlation between scintigraphic, echocardiographic and electrocardiographic
      parameters during LAPT test have been also assessed. Investigations were carried
      out in 55 subjects (Group I: 36 patients with effort angina pectoris; group II:
      controls: 19 clinically healthy subjects). Coronarography was performed in 24
      patients 6 weeks before or after examinations. LATP test was analyzed with ECG,
      ECHO and SPECT. Echocardiography did not increase significantly the LATP test
      diagnostic value. Perfusion scintigraphy enhanced sensitivity and predictive
      excluding value LATP test. These values were 93.3% v 62.9% and 90% v 59.3%
      respectively. LATP test assessed with ECG, ECHO and perfusion scintigraphy
      expressed significantly higher sensitivity and predicting excluding value in
      comparison to ExT. LATP test analyzed in such way was characterized by 100%
      sensitivity and 100% predicting excluding value. CONCLUSION: Combination of LATP
      with electrocardiography, echocardiography and SPECT is a non-invasive high
      quality method for ischaemic heart disease diagnostics.

PMID- 9760805
TI  - [Granulocyte macrophage-colony stimulating factor (GM-CSF) in diagnosis and
      monitoring of non-small cell lung cancer].
AB  - Serum tumor markers may be helpful in early diagnosis of cancer, in the initial
      assessment of the extent of the disease, and in monitoring the tumor growth or
      tumor volume reduction once cancer has been diagnosed and treatment started.
      Recent studies have focused on a new family of markers -hematopoietic growth
      factors, especially on granulocyte-macrophage colony-stimulating factor (GM-CSF).
      A number of investigations have shown autologous production of GM-CSF in various
      human cell lines derived from melanoma, gastric or ovarian cancer, and in certain
      tumors of nonhematopoietic origin. In this study serum level of GM-CSF was
      measured using a sensitive sandwich ELISA system in 34 patients with non-small
      cell lung cancer (NSCLC) before and 10, 30, 90, 180 and 270 days after surgical
      operation. Additionally common accepted tumor markers such as CEA and CYFRA 21.1
      were also assayed. Preoperative level of GM-CSF was significantly increased in
      cancer patients relative to the normal sera (p < 0.02). Concentration of GM-CSF
      and CYFRA 21.1 were decreased on 10th day, but CEA on 30th day after surgical
      treatment, although upon comparison of pre- and postoperative tumor markers serum
      levels significant difference was observed for CYFRA 21.1 (p < 0.05). Levels of
      GM-CSF were increased in 85%, CEA in 62% and CYFRA 21.1 in 51%. The diagnostic
      sensitivity and serum levels of GM-CSF were related to the stage of the disease
      and the combined use of two markers increased the sensitivity compared with the
      use of only one. These results suggest that GM-CSF, especially in the combination
      with CYFRA 21.1., may be useful in the diagnostic and monitoring of patients with
      NSCLC.

PMID- 9760806
TI  - [Polymorphism of the ACE gene and left ventricular morphology and function in
      patients with borderline, mild and moderate hypertension].
AB  - It has been reported that the allel D of an insertion/deletion (I/D) polymorphism
      of the angiotensin I converting enzyme (ACE) gene is associated with the
      conditions of increased cardiovascular risk, including the left ventricular
      hypertrophy and the dysfunction. We examined the relation between the genotype of
      ACE gene and the left ventricular function in normotensives and in borderline,
      mild and moderate hypertensives. We investigated 128 subjects, 47 first-diagnosed
      untreated hypertensives and 81 normotensives. The M-mode and Doppler
      echocardiography were used to quantify LV mass and function. The
      insertion/deletion ACE polymorphism was identified using polymerase chain
      reaction. Left ventricular indexes of the morphology and function were analyzed.
      We compared ambulatory blood pressure profiles between all genotypes in both
      groups. There were no significant differences in indexes of the left ventricular
      hypertrophy in studied normotensives and borderline to mild hypertensives. Our
      results indicate that allel I might be associated with selected parameters of
      diastolic function, while allel D with selected parameters of systolic function,
      of the left ventricle. Results of this study suggest also probable relation
      between allel D and variability of the diastolic arterial pressure in both
      investigated groups.

PMID- 9760807
TI  - [Combined hemostatic defects in family members of symptomatic carriers of Leiden
      mutations of factor V].
AB  - The aim of the study was to determine the frequency of additional prothrombotic
      defect in family members of 14 symptomatic, heterozygous carriers of factor V
      Leiden mutation (FV Leiden). The FV Leiden was found in fifty-five from among 127
      persons (43%). Thirty-two from 53 (68%) family carriers of FV Leiden had venous
      thromboembolic disease at the time of examination. Combined defects were found in
      6 out of 14 families (in 4 families coexistence of FV Leiden mutation with
      protein S deficiency, in 1 with G20210 A mutation of prothrombin gene and in 1
      with antithrombin III deficiency). Until now 63% (7/11) of combined defect
      carriers (mean age 48.5 years) and 59% (24/42) of heterozygous FV Leiden carriers
      (mean age 52.2 years) have been symptomatic. The thrombosis-free survival (Kaplan
      Maier analysis) was comparable in combined and in single defect carriers groups.

PMID- 9760808
TI  - [Erythropoietin in the pathogenesis of anemia in patients with multiple myeloma].
AB  - Anemia is a common symptom in multiple myeloma (MM) patients but the pathogenesis
      of it is still unknown. The aim of the study was to explain the causes of anemia
      in MM patients. Peripheral blood count, bone marrow aspirate, iron and ferritin
      level, serum erythropoietin (EPO) level, T cell subsets and in vitro CFU-E count
      were analyzed in the group od 31 MM patients. Erythropoietin and iron deficiency
      in the study group were not observed. EPO serum level was not significantly
      different in patients with multiple myeloma and in comparison to patients with
      sideroblastic anemia with solid tumors. Absolute CD8 T lymphocyte count was not
      significantly increased in the study group. CFU-E colonies count in vitro was not
      decreased in these patients. CONCLUSIONS: In the study group of the MM patients
      anemia probably does not depend on EPO production. Diminished proliferative
      response of erythropoietic cells on normal serum level of EPO and abnormal iron
      utilisation probably occur in these patients. Replacement of normal
      erythropoiesis by tumor plasma cells is probably not decisive.

PMID- 9760809
TI  - [Surgical treatment of aortic valve disease in patients with severe left
      ventricular failure].
AB  - Two patients with aortic stenosis and severe left ventricle failure who underwent
      aortic valve replacement with satisfactory outcome were presented. Case report.

PMID- 9760810
TI  - [Difficulties in distinguishing left ventricular aneurysm from pseudoaneurysm.
      Case report].
AB  - A case of 51-year old female with large inferior left ventricular aneurysm
      developed 3 months after myocardial infarction is presented. The patient
      demonstrated advanced congestive heart failure and angina. Coronarography
      revealed amputation of the distal part of 3 coronary vessels without possibility
      of revascularisation. In ventriculography large inferior wall aneurysm was found.
      Echocardiography strongly suggest the presence of pseudoaneurysm. During the
      operation very large real aneurysm arising from inferior wall and apex was found.
      Postoperative period was complicated by many cardiac and non cardiac events.
      Authors discuss the problems of proper diagnostic and its influence on decision
      about surgical management.

PMID- 9760811
TI  - [Current opinions on the role of hemostatic factors in the pathogenesis of
      coronary artery disease].

PMID- 9760812
TI  - [Babesiosis-disease of humans and animals].

PMID- 9760813
TI  - [Cytokines in multiple myeloma].

PMID- 9760814
TI  - [The role of monocyte chemotactic peptide (MCP-1) in chronic renal allograft
      rejection].
AB  - Monocyte chemotactic peptide-1 (MCP-1) plays a key role as a mediator of
      inflammatory infiltration, mainly composed with macrophages. Experimental studies
      showed that macrophages and their products are pathogenetic factors of chronic
      renal graft rejection (ch.g.r.). The objective of the present study was to
      determine the role of MCP-1 in the pathogenesis of human renal ch.g.r. Examined
      were 34 patients with ch.g.r. (Group I), 50 patients with a stable allograft
      function (Group II), and 25 healthy subjects (control). Serum and urine levels of
      MCP-1 were measured by ELISA. The serum level of MCP-1 was found to be higher in
      transplant patients, than in control group, but this difference was not
      significant. The serum level of MCP-1 showed a correlation with concentration of
      triglycerides in both transplant patient groups. This may results from
      overproduction of MCP-1 through cells of vascular wall affected by hyperlipidemic
      microenvironment. Considering the lack of relationship between the serum and
      urine levels of MCP-1, I decided attribute the urine levels of MCP-1 to the
      secretion through the infiltrating cells and through the kidney cells. In
      patients with ch.g.r. the urine levels of MCP-1 were significantly higher p <
      0.001) than in patients with a stable graft function and control group. MCP-1
      levels were particularly high (> 2000 pg/mg creatinine) in patients with enhanced
      dynamics of ch.g.r. The MCP-1 levels were higher in those patients whose biopsies
      described cellular infiltration (1385 + 820 pg/mg creatinine vs 680 + 280 pg/mg
      creatinine). The urine level of MCP-1 showed a correlation with concentration of
      serum creatinine, cholesterol, level of proteinuria and with arterial pressure in
      ch.g.r. patients. Increased urine levels of MCP-1 and correlation of MCP-1 with
      the activity of progressive deterioration of the graft function suggest important
      role of this chemokine in the pathogenesis of ch.g.r., possibly by activating
      macrophages and by stimulating their influx into the vascular wall, glomeruli and
      interstitial tissue. Relationship of urinary MCP-1 excretion with arterial
      hypertension and lipid disorder suggest that the effect of those risk factors for
      a progressive deterioration of graft function manifest on the molecular level by
      affecting the generation of MCP-1.

PMID- 9760815
TI  - [Levels of 1,25-dihydroxyvitamin D3 concentration in renal venous blood serum of
      patients with renovascular hypertension caused by unilateral renal artery
      stenosis].
AB  - Functionally significant, unilateral renal artery stenosis is characterized by
      reduced renal perfusion and lateralization of both excretory and endocrine
      function. The present study aimed to assess the influence of unilateral renal
      artery stenosis on plasma 1,25-dihydroxyvitamin D3 level. In sixteen patients (10
      males and 6 females) with unilateral renovascular hypertension blood samples for
      estimation of plasma renin activity (PRA) and 1,25-dihydroxyvitamin D3
      concentration were withdrawn from the renal vein of the ischaemic and normal
      kidney, from the femoral artery and from the vena cava inferior distally to the
      orifices of renal veins. Significantly elevated PRA (20.1 +/- 4.52 ng/ml/h vs 6.0
      +/- 1.76 ng/ml/h, p < 0.005) but significantly reduced level of 1,25
      dihydroxyvitamin D3 (99.25 +/- 4.8 pmol/l vs 115.75 +/- 6.7 pmol/l, p < 0.05)
      were found in renal vein blood of the ischaemic kidney as compared with the
      respective values of the normal kidney. No significant correlation was found
      between PRA and 1.25-dihydroxyvitamin D3 irrespective of the site of blood
      withdrawal. CONCLUSION: Renal ischaemia seems to exert a suppressive effect on
      1,25-dihydroxyvitamin D3 synthesis by the kidney.

PMID- 9760816
TI  - [Markers of bone formation and resorption in primary and secondary
      hyperparathyroidism].
AB  - Hyperparathyroidism, both primary and secondary in chronic renal failure, leads
      to pathologic changes in the bones. Newly introduced markers of bone metabolism
      enable to biochemically detect and evaluate these changes. The aim of our studies
      was to perform determinations of serum osteocalcin as a marker of bone formation,
      and C-terminal telopeptide of collagen I (ICTP) as a marker of bone resorption in
      patients with excessive secretion of parathyroid hormone (PTH). Our studies
      comprised of 15 patients with primary and 24 patients with secondary
      hyperparathydroidism. In all patients serum PTH, osteocalcin and ICTP were
      detected by radioimmunoassay; the correlations between PTH and osteocalcin as
      well as between PTH and ICTP were also performed. Serum PTH was elevated in both,
      primary and secondary hyperparathyroidism. In primary hyperparathyroidism serum
      osteocalcin was moderately or definitely elevated, similarly serum ICTP was high.
      Following surgical removal of a parathyroid adenoma, concomitantly with a drop in
      serum PTH there was a rapid normalization of serum osteocalcin and ICTP.
      Secondary hyperparathyroidism in uraemia was characterised by markedly elevated
      serum osteocalcin and ICTP which surpassed the concentration of these markers in
      primary hyperparathyroidism. There was a positive correlation between serum PTH
      and osteocalcin levels, and a lower correlation between PTH and ICTP. From our
      studies it is concluded that excessive secretion of PTH in primary and secondary
      hyperparathyroidism stimulates bone formation and to higher degree--bone
      resorption.

PMID- 9760817
TI  - [The effect of pentoxifylline on oxidative metabolism in neutrophils primed with
      tumor necrosis factor alpha in patients with stable angina pectoris].
AB  - In 14 patients with stable angina pectoris we examined the effect of
      pentoxifyline (PTX) on oxidative metabolism of TNF-alpha-priming neutrophils. The
      control group consisted of 21 patients with stable angina pectoris without
      pentoxifylline administration. Blood samples for examination were taken from
      basilic vein (peripheral blood) and coronary sinus immediately before PTCA
      procedure. In PTX-group was found the significant decrease in spontaneous CL of
      TNF-alpha-priming neutrophils from coronary sinus blood (1231.0 +/- 119.4 mV x
      min), in comparison to the control group (1374 +/- 124.4 mV x min). In PTX-group
      was found the significant decrease in fMLP stimulated CL of TNF-alpha-priming
      neutrophils from peripheral blood (4219.0 +/- 707.2 mV x min) and coronary sinus
      blood (4322.0 +/- 664.4 mV x min), in comparison to the control group (5248.0 +/-
      595.8 mV x min and 4973.0 +/- 536.5 mV x min; respectively). There were no
      differences between both groups in PMA stimulated CL of TNF-alpha-priming
      neutrophils.

PMID- 9760818
TI  - [Levels of tumor necrosis factor alpha in serum of patients with
      hyperlipoproteinemia IIB before and after micronized fenofibrate therapy].
AB  - Tumor necrosis factor alpha (TNF alpha) secreted by activated macrophages
      stimulates proliferation and migration of vascular smooth muscle in
      atherogenesis. Up to now, the effect of fibrates on concentration of TNF-alpha
      has not been investigated. The aim of this study was to estimate TNF-alpha plasma
      concentration in healthy subjects before and after fenofibrate therapy in
      patients with hyperlipoproteinaemia IIb and to correlate their levels with plasma
      concentration of total cholesterol (TC), low density lipoproteins (LDL) and
      apolipoprotein B (ApoB). METHODS: 10 patients with hyperlipoproteinaemia IIb were
      treated with micronized fenofibrate (Lipanthyl 200 m-Fournier) for 1 month.
      Cytokines levels before and after therapy was measured by the ELISA method with
      Genzyme kits. RESULTS: The levels of lipid parameters at the onset study were as
      follows: TC: 265.4 +/- 9.4 mg%, TG: 344 +/- 53 mg%, LDL: 167.2 +/- 4.7 mg%, and
      ApoB: 1.62 +/- 0.05 g/l. After 1-month therapy with Lipanthyl 200 m the
      parameters decreased: TC 206 +/- 16 mg% (p < 0.05), TG: 194 +/- 30 mg% (p <
      0.05), ApoB: 1.43 +/- 0.04 g/l (p < 0.01), and LDL: 144.4 +/- 12.9 mg% (ns). The
      decreased level of TC, TG and LDL correlated with the decreased concentration of
      TNF alpha. Before treatment the TNF concentration was 19.2 +/- 1.6 pg/ml and was
      higher than the concentration of control subjects (9.9 +/- 1.1 pg/ml, p < 0.01).
      After 1-month therapy the level of TNF alpha in blood from patient was 9.2 +/-
      1.0 pg/ml (p < 0.01). The results of this study indicate that the concentrations
      of TNF alpha in plasma from hyperlipidemic patients are higher than
      concentrations of healthy subjects. Fenofibrate decreased the levels of this
      cytokine. This effect may be of significance for the treatment of HLPIIb and of
      atherosclerosis prevention.

PMID- 9760819
TI  - [Levels of L-carnitine in serum of patients with chronic renal failure treated by
      hemodialysis (HD)].
AB  - Low serum levels of the carnitine in chronic uremic patients treated by
      hemodialysis is one of the causes of muscle weakness. In 50 patients with chronic
      renal failure treated by HD and in 13 nondialyzed patients EMG and measurement of
      nerve conduction velocity were performed. In 25 of 50 patients treated with HD
      and in 13 non-dialyzed patients serum concentration of free and total carnitine
      were measured. In HD patients serum level of carnitine was significantly lower as
      compared to the control group of healthy subjects and to the nondialyzed
      patients. In all patients the EMG investigations showed the traits of the
      neurogenic atrophy of the muscles. The correlation between the amplitude of
      muscle potentials and serum levels of carnitine suggests that the depletion of
      carnitine may play a role in severity uremic myopathy.

PMID- 9760820
TI  - [Evaluation of the rate for reaching steady state during oral propafenone therapy
      in patients with ventricular arrhythmias].
AB  - We prospectively evaluated reaching of steady state and clinical efficacy of
      propafenone (PPF), class Ic antiarrhythmic agent, in 16 patients (pts) (age 46
      69, mean 57 years) with symptomatic ventricular arrhythmias (Low class II and
      IV). The majority (13 pts) had coronary artery disease. Drug was administered for
      7 days (daily dose: 3 x 150 mg). Efficacy was defined as > 80% reduction of
      ventricular premature complexes (VPC) and class IV elimination in 24-hours Holter
      recording. Responders were continued on PPF for 3 weeks, in non-responders dose
      was titrated to 900 mg a day for the next 7 days. After second Holter evaluation
      the treatment was continued for 2 weeks in responders group. The non-responders
      were switched to other drug. After 4 weeks final Holter monitoring was performed.
      Serum concentration of PPF and its 2 metabolites: 5-hydroxy PPF and N-depropyl
      PPF were determined in 2, 3, 4, 5, 6, 7th day, just before the morning dose (3 x
      150 mg/day) in 9 pts. RESULTS: Trough serum concentrations of PPF differed in
      high degree: 0-226 ng/ml (2nd day), 22-438 ng/ml (4th day), 42-614 ng/ml (6-7
      day). An increasing tendency of serum concentrations of PPF was observed, so
      steady-state was not reached. This great dispersion of concentration values is
      because of non-linear metabolism and individual differences. Defined efficacy
      critetion was achieved in 62% pts, 56% for lower dose. Mean frequency of VPC was
      reduced by 86% in 24-hour Holter recording and per hour (p = 0.0011). Reduction
      of couplets/24 h was 87% (p = 0.0175). Significant prolongation of PQ (14%, p =
      0.009) and QRS (13%, p = 0.0052) were observed. Changes of QT interval were not
      significant. One case of proarrhythmia was the cause of stopping the treatment.
      CONCLUSIONS: Serum concentrations' values undermine common opinion, that steady
      state can be reached after 1-2 days of treatment. High dispersion of serum levels
      is the result of nonlinear metabolism of PPF and individual differences. In spite
      of this the study showed defined antiarrhythmic efficacy in 62.5% pts. In this
      group 90% success rate was achieved after lower dose 3 x 150 mg.

PMID- 9760821
TI  - [Hematological problems in patients with bronchial cancer].
AB  - Four patients with lung cancer and hematological disorders occurring in different
      stages of the disease are presented. In three out of them cancer metastases were
      found prior to the discovery of the primary focus. In two patients those
      metastases were localized in the bone marrow resulting in the hematological
      picture of the myelodysplastic syndrome and osteomyelofibrosis. In one of them
      acute lymphoblastic leukemia developed after short-lasting remission involving
      the regression of bone marrow metastases of the cancer. In one patient lymph node
      enlargement, constitutional symptoms and laboratory signs of inflammation led to
      the preliminary diagnosis of Hodgkin disease. In the remaining patient acute
      leukemia resistant to chemotherapy developed 34 month after the diagnosis of lung
      cancer. Our observations point to the necessity of the through diagnosis in every
      case of hematologic abnormalities of unknown origin and the search of a possible
      underlying malignancy.

PMID- 9760822
TI  - [Patent ductus arteriosus (Botall). Modern treatment patterns in children and
      adults].

PMID- 9760823
TI  - [Watermelon stomach--etiopathogenesis, diagnosis, differentiation and treatment].

PMID- 9760824
TI  - [Aminoglycoside antibiotics--should they be administered in a single dose?
      Practical point of view].

PMID- 9760825
TI  - [Professor Karel Horky awarded with the honorary medal of the Polish Society of
      Internal Medicine].

PMID- 9760826
TI  - [Mechanisms of multidrug resistance in tumor cells and analytical methods for its
      detection].
AB  - We reviewed mechanisms of multidrug resistance (MDR) phenotype in tumor cells and
      evaluated analytical methods for detection of clinical MDR. A well-recognized
      mechanism of MDR phenotype is the induction and increased expression of P
      glycoprotein (P-gp) which is a 170 kDa cellular transmembrane protein encoded by
      a multidrug-resistance 1 gene (MDR1) and works as a drug efflux pump. Cellular
      MDR phenotype through P-gp/MDR1 can be detectable at protein level by: (1) using
      immunohistochemical method, flow cytometric assay and Western blot analysis with
      monoclonal antibodies against human P-gp, and (2) measuring Rhodamine 123 dye
      efflux as a functional assay of P-gp. Molecular knowledge and recent technical
      progress enable to determine MDR1 gene expression by RT-PCR-based analytical
      methods as well as conventional quantification methods of gene expression such as
      Northern blot analysis. In the evaluation of P-gp/MDR1 expression in clinical
      samples, in which amount of materials was limited, utilization of simple and
      sensitive methods like competitive RT-PCR assay might be efficacious for its
      quantitative detection in clinical laboratories. Evidences which showed the
      positive correlation between the expression of P-gp/MDR1 and clinical resistance
      or refractoriness of tumor cells to anticancer drugs involved in MDR have been
      accumulated and support the clinical importance of its detection to circumvent
      resistance with alternate use of non-MDR drugs.

PMID- 9760827
TI  - [Age-related changes of electrocardiographic wave].
AB  - Magnetocardiograms (MCGs) were recorded by means of a second-derivative SQUID
      (superconducting quantum interference device) magnetometer in 150 normal subjects
      (25-34 years old, 30 cases; 35-44 years old, 30 cases; 45-54 years old, 30 cases;
      55-64 years old, 30 cases; 65-74 years old, 30 cases) to investigate whether
      cardiac current would change with age. Based on these MCG records at 36 points on
      the anterior chest wall, isomagnetic maps during QRS wave were constructed, and
      dipole moments was calculated mathematically. The amplitude of RV5 and SV1 + RV5
      in ECG were larger in 65-74-year-old women compared to those in women of other
      ages, and SV1 + RV5 was smaller in 45-74-year-old men compared to those in 25-44
      year-old men. However, dipole moments deduced from MCG did not differ with age.
      These results suggest that age-related changes in the amplitude of QRS wave in
      ECG do not affect the change in electromotive force with aging.

PMID- 9760828
TI  - [Association of bone mineral density with vitamin D receptor gene polymorphism-
      changes in radial bone mineral density with long-term follow-up: longitudinal
      study].
AB  - Recent studies have shown that genetic effects on bone mineral density (BMD) and
      bone turnover are related to vitamin D receptor (VDR) gene polymorphism. However,
      discordant studies have been published and it is still not clear whether VDR
      genotypes influence bone mass accretion and/or postmenopausal bone loss. To
      assess allelic influence of the VDR gene on BMD, we determined changes in 1/6
      radial-BMD by several repeat measurements in the same subjects for about ten
      years and analyzed VDR polymorphism of BsmI restriction enzyme in 53 normal
      healthy Japanese women (age: 50.3 +/- 4.7 years, mean +/- SD). Twenty-seven (age:
      53.2 +/- 4.7 years) of the subjects were post-menopausal (POST group). Among
      these 53 subjects, the distribution of bb, Bb and BB genotypes was 64.2%, 34% and
      1.9%, respectively. The genotype frequencies in this study were very similar to
      those in previous reports concerning other Japanese women. There was no
      difference between the b group (women with bb genotype) and B group (women with
      BB or Bb genotype) in age, body weight, height, body mass index (BMI), years
      since menopause, serum osteocalcin and serum alkaline phosphatase values. In the
      POST group, BMD of the B group at menopause was lower than that of the b group (p
      < 0.05). About ten years after menopause, BMD did not differ significantly
      between these groups because the decrease in BMD in the b group was larger than
      that in the B group. Regarding changes in BMD in the POST group for four years
      after menopause, BMD of the b group was significantly decreased compared with the
      B group (p < 0.01). Our findings suggest that the differences in BMD by VDR
      genotype were larger among pre- and pri-menopausal women and seemed to decrease
      with years after menopause. It is suggested that there are other factors
      influencing BMD and postmenopausal bone loss in elderly women.

PMID- 9760829
TI  - [Characterization and problems regarding clinical reference ranges of aged
      subjects on clinical chemistry].
AB  - Various characteristic clinical laboratory testing data related to clinical
      chemistry were collected from 11 institutes across the nation, and age-related
      clinical reference values, reference intervals and within-subject biological
      variations were calculated. Using these calculated results, characterization of
      aged-related reference ranges and the method of determining an aged subject's
      testing values were investigated. From these results, the following facts became
      clear. Estimation of health-associated reference intervals for aged subjects was
      very difficult. As the aged subject's reference values differ remarkably by sex
      and age on several test items, sex- and age-related clinical reference values are
      necessary. In case of the mass screening survey which utilizes preceding healthy
      values, we should decide by within-subject biological variation. We usually use
      reference ranges to decide whether the measured values are located within these
      ranges, and must use a differential value to speculate regarding a particular
      disease. These results indicate that multiple standard must be prepared for each
      clinical laboratory testing value, and that it is ideal to be able to select a
      suitable standard for the subjects state. To select a suitable standard
      clinically, we need an expert system. For this purpose, much more basic data
      concerning reference ranges, differential values and so on must be accumulated.

PMID- 9760830
TI  - [Lipid peroxide and antioxidants in the elderly].
AB  - Aging is associated with changes in physical characteristics and decline of many
      physiological functions. The aging process have been described by various
      theories, in particular the free radical theory of aging has received widespread
      attention. It has been accepted that the oxidative stress or damage induced by
      free radicals is related to aging. In this study, we determined the serum
      concentration of lipid peroxide and antioxidant as biomarker for aging. Healthy
      subjects were classified into 3 groups, elderly (65-), middle-aged (40-64) and
      young group (20-39). Findings in the elderly were as follows: 1. Lipid peroxides
      in the elderly group were significantly higher than those in the young group. 2.
      Preventive antioxidant concentrations of superoxide dismutase, glutathione
      peroxidase and albumin were lower than those in the young group, but
      ceruloplasmin values increased and catalase activity was unchanged. 3. The total
      antioxidant capacity of serum was slightly decreased. 4. Superoxide generation by
      neutrophils while resting was significantly higher in the young group.

PMID- 9760831
TI  - [A feature of hematological findings in myelodysplastic syndromes].
AB  - Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis in
      one or more hematopoietic lines with abnormal morphology and peripheral blood
      cytopenia. Primary MDS are more common in elderly patients and rare in children
      and young adults. The diagnosis of MDS in patients with unexplained cytopenias
      requires careful morphologic evaluation of both the peripheral blood and bone
      marrow cells. To examine which abnormalities detected by routine examination
      suggest MDS, we analyzed the hematological findings of peripheral blood in
      seventy-six cases of MDS. Anemia (> 60%), leukopenia (> 40%), thrombocytopenia (>
      70%) as well as blast (> 40%) were often found. The prevalence of MDS was
      relatively high in patients with morphological abnormalities such as elliptocyte,
      dacryocyte, erythroblast, pseudo-Pelger-Huet anomaly, decreased secondary
      granules and giant platelets. Careful attention should be paid to these findings
      especially elderly patients, since these may provide clues to the diagnosis of
      MDS.

PMID- 9760832
TI  - [Gene therapy for hematological malignancies].

PMID- 9760833
TI  - [Lactate metabolism and lactic acidosis].
AB  - Lactate can be viewed as a metabolic dead end in that it can only be produced or
      utilized via pyruvate. Lactate production is determined primarily by pyruvate
      concentration and to a lesser extend by the redox state. Increased lactate
      production may result from tissue hypoxia, alkalosis, catecholamine and alanine
      transamination to pyruvate. Hyperlactatemia is observed in many pathological
      conditions. Current diagnostic criteria for lactic acidosis are a pH less than
      7.35 and lactate concentration greater than 5 to 6 mmol/l. In our study series,
      malignancy was the most common underlying disease accompanied by lactic acidosis.
      Organ failure, cardiovascular disease and diabetes mellitus were also common. The
      prognosis of patients with these diseases were grave. In cases of lactic acidosis
      associated with diabetes mellitus, alcoholic liver disease, rhabdomyolysis and
      diabetic comas were noticeable as complications. Alcohol abuse was the most
      common cause of lactic acidosis associated with diabetes mellitus. In these
      cases, laboratory data showed prominent hyperlactatemia, hyperglycemia and
      acidemia and elevated anion gap. The mortality rate in these cases was 36% and
      higher in cases with organ failure. Treatment of lactic acidosis consists of
      alkalization by sodium bicarbonate with carbicarb, insulin-glucose-infusion,
      dichloroacetate therapy, tham administration, bicarbonate-buffered peritoneal
      dialysis and high bicarbonate-containing dialysis.

PMID- 9760835
TI  - [The role of chemokines such as RANTES in allergic disease].
AB  - Much attention has recently been focused on the role of allergic inflammatory
      reaction in asthma. Eosinophils are considered to be the major type of
      inflammatory cell involved in bronchial asthma, since eosinophil-specific granule
      proteins can damage bronchial mucosal cells. Chemokines related to the beta
      subfamily, the so-called platelet factor 4 (PF4) superfamily have been shown to
      stimulate human eosinophils or basophils, and are considered to be important
      mediators of inflammation. RANTES may be released from activated platelets and is
      considered to play an important role in various immune and allergic disorders.
      RANTES is a potent chemoattractant for various inflammatory cells such as
      eosinophils, as well as for memory T cells and monocytes, thus potentially
      recruiting these cells from the circulation to an inflamed focus. Involvement of
      eosinophils and T cells in bronchial asthma has also been reported. To extend our
      understanding of the participation of eosinophils, T cells, and RANTES in the
      pathogenesis of allergic disease, we demonstrated the important roles of
      chemokines such as RANTES in allergic disease.

PMID- 9760836
TI  - [Molecular mechanism of interleukin-8 gene expression].
AB  - Evidence is accumulating that interleukin-8 (IL-8), discovered as a potent
      neutrophil chemotactic factor, plays a crucial role in establishing acute
      neutrophil-mediated inflammation by exerting various activities against non
      leukocytic as well as leukocytic cells. Various types of cells can rapidly
      produce a large amount of IL-8 upon stimulation with inflammatory stimuli, such
      as lipopolysaccharide, IL-1, and tumor necrosis factor (TNF). However, IL-8
      production is tightly regulated at several levels, particularly at the
      transcriptional levels to prevent aberrant production. Our previous experiments
      demonstrated that IL-8 gene transcription requires the cooperative activation of
      a transcription factor, NF-kappa B, with an additional transcription factor, AP-1
      or NF-IL6, depending on types of cells and stimuli. In addition, we recently
      observed that infection with Helicobacter pylori or cytomegalovirus activated NF
      kappa B, therapy inducing IL-8 protein secretion as well as IL-8 gene
      transcription. Moreover, IL-8, in turn, enhanced cytomegalovirus replication and
      infectious virion production. Collectively, these results suggest the potential
      involvement of IL-8 in the pathology of bacterial or viral infection.

PMID- 9760837
TI  - [The examination of apoE phenotypes in diabetic patients with peripheral
      neuropathy].
AB  - Apolipoprotein E (apoE), which is reported to recognize the low density
      lipoprotein receptor and remnant receptor, mediates the delivery of cholesterol
      and other lipids to the cells all over the body. There are several phenotypes
      such as apoE2, apoE3 and apoE4. Recently, it is reported that apoE plays an
      important role in neurite outgrowth. To determine whether apoE phenotype is
      concerned in diabetic peripheral neuropathy, we investigated the incidence of
      apoE phenotypes in diabetic patients with peripheral neuropathy. The occurrence
      of retinopathy and nephropathy were not different in apoE2, apoE3 and apoE4.
      However, the frequency of diabetic neuropathy was higher in apoE4 than apoE2 and
      apoE3 (p < 0.05). Furthermore, as the stage of diabetic neuropathy advanced, the
      incidence of apoE4 increased. From these results we conclude that apoE phenotype
      influences the progress of diabetic peripheral neuropathy and that apoE4
      contributes to the deterioration of diabetic peripheral neuropathy.

PMID- 9760838
TI  - [Basic evaluation for new antimicrobial susceptibility testing of Mycobacterium
      tuberculosis by bioluminescence assay of mycobacterial ATP].
AB  - It has been reported that the number of living bacteria is correlated to their
      ATP contents. Based on this, ATP measurement was applied to the susceptibility
      test for Mycobacterium tuberculosis to antimicrobial agents. ATP was extracted
      from the bacterial suspension prepared from M. tuberculosis H37Rv grown on 1%
      Ogawa medium and measured by bioluminescent assay. The highest relative light
      units (RLU) was obtained when ATP was extracted with the reagent supplied by
      Kikkoman Inc. (Chiba, Japan) at 100 degrees C for 3 minutes. The amounts of ATP
      recovered was constant at 100 degrees C for 8 minutes. The ATP contents
      correlated well with the number of bacteria expressed as CFU. The ATP contents of
      M. tuberculosis H37Rv inoculated into the Middlebrook 7H9 broth medium containing
      antituberculous agents were measured at days of 0, 3, 5 and 7. The control
      culture showed the time-dependent increase in the RLU values, while cultures
      supplemented with antimicrobial agents reduced their ATP contents concomitant
      with the concentrations of drugs. The growth of tubercle bacilli was expressed as
      RLU ratio, the ratio of RLU in the drug-containing cultures to those in drug-free
      ones. RLU ratio of 0.5 or less was determined as sensitive and the ratio of more
      than 0.5 as resistant to drugs. The inoculum size of bacteria did not affect the
      days giving RLU ratio below 0.5 or 0.3. Within 7 days, susceptibilities to drugs
      could be determined. In conclusion, this test is simple, rapid, sensitive and
      highly reproducible and useful for the assessment of susceptibility.

PMID- 9760839
TI  - [Protein-RNA molecular mimicry].

PMID- 9760840
TI  - [A bacterial RNA that functions both as a tRNA and an mRNA].

PMID- 9760841
TI  - [Early events occurring during light signal transduction in plants].

PMID- 9760842
TI  - [Dynamic structural changes of the linear chromosomes of streptomyces and the
      origin and evolution of chromosomes].

PMID- 9760843
TI  - [Mechanism of biological methane formation structure and function of methyl
      coenzyme M reductase].

PMID- 9760844
TI  - [Crystal structure of lambda-exonuclease].

PMID- 9760845
TI  - [Optical oxygen sensing technology using methallo-porphyrins].

PMID- 9760846
TI  - [Therapeutic goals for blood pressure in the press].

PMID- 9760847
TI  - [Surgeons on trial].

PMID- 9760848
TI  - [Food and health--an international perspective].

PMID- 9760849
TI  - [Is methadone a solution?].

PMID- 9760850
TI  - [Is methadone efficient? Methadone therapy versus evidence-based medicine].

PMID- 9760851
TI  - [Aerobic capacity in children and adolescents--Nordic results over the past 45
      years].
AB  - The aim of this study was to reveal whether today's children and adolescents have
      lower aerobic capacity compared with earlier studies. Aerobic capacity may be
      defined as the highest amount of oxygen a subject is able to consume per unit of
      time. Peak oxygen uptake (VO2peak) is often used as a measure of aerobic capacity
      in children. VO2peak in 196 healthy children and adolescents of both sexes, aged
      8-16 years, was measured on a graded treadmill test. The mean results of VO2peak
      (l.min-1) showed only small differences compared with previous studies in
      Scandinavia. There was, however, greater dispersion in the present study when the
      VO2peak-values were corrected for weight (ml.kg-1.min-1) than in the earlier
      studies. When compared to other countries in Europe, Norwegian subjects achieved
      higher values. The reason may be due to either genetic differences or to a higher
      level of physical activity among the Norwegian subjects.

PMID- 9760852
TI  - [Blood pressure measurements using three different cuff sizes].
AB  - The use of blood pressure cuffs containing bladders of appropriate size for the
      arm is a known prerequisite for correct blood pressure measurements. The Tricuff,
      containing three inflatable bladders of varying dimensions, one of which is
      automatically selected to fit the arm circumference, was compared to a standard
      cuff (12 x 35 cm) in 137 persons. In persons with large arms (circumference > or
      = 32 cm) measurement with the Tricuff showed on average 19.2 mm Hg lower systolic
      pressure and 12.9 mm Hg lower diastolic pressure than with the standard cuff. In
      persons with small arms (< 32 cm) the corresponding differences were 9.0 mm Hg
      and 7.5 mm Hg. Compared to the Tricuff, the standard cuff overestimates blood
      pressure in people with a large arm circumference. Overestimation may also be
      caused by the rubber bladder bulging more from below the standard soft nylon cuff
      than what the firmer texture of the Tricuff allows, resulting in falsely high
      values even in persons with normal arm circumference.

PMID- 9760853
TI  - [Invagination in children].
AB  - Although rare, childhood intussusception is one of the most common causes of
      small bowel obstruction in infancy. In these very young patients it can sometimes
      be difficult to interpret the clinical signs and symptoms correctly. This
      retrospective study comprises 79 children (median age 7.5 months; 24% girls and
      76% boys) who experienced 83 episodes of intussusception. At admission the
      diagnosis made by the referring physicians could be confirmed in only about one
      third of the cases. A barium enema was part of the inhospital diagnostic process.
      Non-operative treatment was attempted in 70 patients (89%), and barium enema
      reduction was successful in 64%. Laparotomy was required in 33 (42%) of the
      patients. No mortality, bowel perforation, or any other major complications were
      encountered. The diagnosis of childhood intussusception seems difficult to
      achieve in many cases, and the interpretation of, at times vague clinical signs
      and symptoms remains a challenge for all clinicians who are involved in the care
      of these very young patients.

PMID- 9760854
TI  - [Cerebral amyloid angiopathy].
AB  - Cerebral amyloid angiopathy affects the cerebral vasculature selectively, and
      there is no systemic amyloidosis. Amyloid is deposited in small and medium-sized
      vessels of the cortex and leptomeninges. Cerebral amyloid angiopathy is a common
      cause of spontaneous lobar haemorrhage in elderly patients. However, cerebral
      amyloid angiopathy may have atypical clinical and radiological presentations. We
      report on five patients (three males and two females, aged 43-77 years) with
      histologically verified cerebral amyloid angiopathy. One patient experienced an
      acute headache attack and classical lobar haemorrhage. The other patients had
      various neurological symptoms and signs, such as seizure, disturbed vision,
      pareses, aphasia, and dementia that were initially diagnosed as cerebral
      infarction or tumour. Two patients with cerebral amyloid angiopathy and
      granulomatous angiitis responded to immunosuppressive treatment.

PMID- 9760855
TI  - [Ataxia due to vitamin E deficiency].
AB  - Few metabolic or degenerative ataxias can be treated pharmacologically. However
      ataxia due to vitamin E deficiency can be treated effectively with vitamin E
      supplementation if it is diagnosed early. We describe two ataxic patients with
      vitamin E deficiency where this was the definite or probable cause of the ataxia.
      Both polyneuropathy and cerebellar dysfunction were found. The deficiency was due
      to intestinal resection in one case, whereas the exact mechanism was unknown in
      the other case. In one of the patients there was a clear improvement of the
      ataxia after vitamin E supplementation, but this had to be taken for about six to
      12 months. In the other patient the symptom progression was halted, but only
      slight improvement was observed. This patient therefore underwent leftsided
      stereotaxic thalamotomy, which markedly alleviated his rightsided ataxic
      symptoms. We stress the importance of testing for vitamin E (alpha-tocopherol) in
      all patients with ataxia where there is no other known cause.

PMID- 9760856
TI  - [Female urethral diverticulum].
AB  - Female urethral diverticulum is a rare condition. The reported incidence varies
      from 1.4-5%, depending on the population studied. The correct diagnosis is often
      delayed because of unspecific symptoms from the patients' lower urogenital tract.
      The classic triad of female urethral diverticulum is dribbling of purulent
      matter, dyspareunia and dysuria. The majority of patients have a palpable mass
      located on the anterior vaginal wall. The presentation and management of 11 women
      with urethral diverticulum who where admitted to the Surgical Department of the
      Central Hospital in Akershus during the period 1.1. 1975 to 1.4. 1996 is
      reviewed. Investigations included vaginal examination, urethrocystoscopy,
      urography and urethrography with a double balloon catheter. A palpable mass was
      found in all 11 patients. The urethrography was positive in eight out of ten
      patients. Diverticulectomy was performed on nine patients. In follow-up
      interviews from three months to 21 years after treatment, one patient was found
      to suffer from incontinence after surgery, two patients noticed recurrence of
      some symptoms, and six patients were completely relieved of their complaints.

PMID- 9760857
TI  - [What effects does methadone maintenance treatment have on the rehabilitation of
      heroin addicts?].
AB  - The purpose of the study was to determine the effect of methadone maintenance
      treatment on heroin addicts. By searching in Medline and Cochrane Library two
      randomized controlled trials were found where methadone was the main intervention
      in the rehabilitation of heroin addicts. The trials were found among more than
      2,350 articles on various aspects of methadone and were the only ones that met
      our criteria for inclusion in the study. The two studies comprised 347
      participants. Both trials showed that methadone maintenance treatment had a
      positive effect on continuing participation in the treatment programme. One of
      the trials also showed that the treatment lowered the rates of opioid and cocaine
      use. It is alarming that only two randomized controlled trials could be found
      evaluating the effect of methadone maintenance treatment on the rehabilitation of
      heroin addicts. No trials demonstrating the effect of the treatment on mortality,
      crime, prostitution or risk behaviour related to communicable diseases were
      found.

PMID- 9760858
TI  - [Prehospital treatment of heroin intoxication in Oslo in 1996].
AB  - The number of heroin overdoses among drug addicts in Oslo is increasing. In 1996
      overdoses counted for 1,248 (12%) of all emergency call-outs by the ambulance
      service. Heroin can cause fatal respiratory insufficiency, and in 1996 a total of
      104 deaths related to heroin overdoses were reported in Oslo. Heroin overdoses
      are treated on site by ambulance personnel. Advanced cardiopulmonary
      resuscitation was started on 18 of the 79 addicts who were found unconscious, and
      11 persons were treated successfully. A total of 846 drug addicts had to be given
      the antidote naloxone, and among these 678 (80%) persons were found in a coma.
      Only 29 persons had to be transported to hospital. Early treatment probably
      prevented both morbidity and mortality, no time being wasted transporting the
      patients to hospital. Ambulance personnel treat all drug addicts with the same
      respect as they do other patients. They have no police escort; they are familiar
      with the addicts and their environment and they have gained their confidence.
      Prehospital treatment saves on health services resources, and should, in our
      experience, be carried out in collaboration with a hospital or other health
      institutions for mutual and optimal benefit.

PMID- 9760859
TI  - [Air quality and microbiologic contamination in operating theatres].
AB  - The present study concerns the air quality and microbiological contamination in
      two newly built operating theatres; one with laminar air flow (LAF) equipment for
      cardio-thoracic operations, and one with conventional ventilation for urological
      operations. Both theatres had an identical number of air exchanges (17/h),
      identical microclimatic conditions and they employed the same cleaning
      procedures. In the LAF-ventilated operating theatre bacterial contamination of
      the air was effectively reduced to less than 10 colony-forming units (CFU)/m3 in
      all 125 samples (1 m3 per sample) tested. In most samples, 118/125, the bacterial
      count was less than 5 CFU/m3, despite the presence of ten persons. The
      conventionally ventilated theatre reached values up to 120 CFU/m3 during the most
      active period of the day when approximately seven persons were present. The LAF
      ventilation reduced both the content of particles in the air and contamination by
      bacteria on the floor. In both theatres cleaning procedures had only a low impact
      on CFU in the air and on the floor. The use of diathermia markedly increased the
      level of small particles in the air, and this may influence the air quality in
      the operating theatres.

PMID- 9760860
TI  - [Folate and health--new knowledge and new recommendation].
AB  - The dietary intake of folate in Norway is not optimal with regard to minimizing
      the risk of birth defects (especially neural-tube defects), and poSsibly also
      cardiovascular diseases and other diseases. The National Nutrition Council has
      therefore initiated a project to evaluate the status of folate in Norway and to
      recommend actions for necessary improvement. A protective effect of folic acid
      supplements on neural-tube defects has been found in observational studies and
      clinical trials. The effects of folate on cardiovascular diseases and cancer are
      less certain. The estimated average intake of folate from foods in Norway is
      lower than the recommended 300 micrograms per day for adult women and men, and
      remarkably lower than the 400 micrograms per day recommended for pregnant and
      lactating women. Thus, with the aim of minimizing the risk for neural-tube
      defects, the National Nutrition Council now recommends that all women who are
      planning pregnancy or who are likely to become pregnant have an intake of at
      least 400 micrograms folate per day. Because it may be difficult to achieve this
      through diet alone, and because an additional risk-lowering effect of folic acid
      supplementation has been shown, a folic acid supplement of 400 micrograms per day
      is recommended for this group. The supplement should be taken one month before
      conception and during the first two months of pregnancy. Fortification of foods
      with folate is not recommended because some groups may then exceed the
      recommended upper intake level.

PMID- 9760861
TI  - [Intrauterine nutrition].
AB  - Foetal or intrauterine nutrition is a subject of increasing interest. There are
      two main reasons for this. The first one is the observation that being born small
      for gestational age is associated with increased risk of cardiovascular disease
      and diabetes later in life. The second one is the discovery that nutritional
      factors directly influence activity of genes. If nutritional inadequacies in the
      foetal period permanently alter the expression of genes, the individual's
      susceptibility to perinatal complications and diseases later in life may be
      altered. The main causes of intrauterine malnutrition are poor maternal diet,
      placental insufficiency, and impaired foetal usage of nutrients. The consequences
      of foetal malnutrition may include intrauterine growth retardation, congenital
      malformation, a variety of neurological dysfunctions, susceptibility to birth
      asphyxia, and diseases later in life; all of these are important determinants of
      health throughout life.

PMID- 9760862
TI  - [Physicians cannot... A poster on reality orientation in health care].

PMID- 9760863
TI  - [We have to take the Bristol business seriously].

PMID- 9760864
TI  - [A-clinics and treatment of drug addicts].

PMID- 9760865
TI  - [Risk of abuse when using zopiclone].

PMID- 9760866
TI  - [Recruitment to medical research].

PMID- 9760867
TI  - [Do the new instructions from the EU threaten children's health?].

PMID- 9760868
TI  - Physical mapping and activity of ribosomal RNA genes in mussel Mytilus
      galloprovincialis.
AB  - In bivalve molluscs, NOR analysis was carried out by silver staining, and
      extensive intra- and interindividual differences in the apparent number of NORs
      were reported. In this work, we determine the physical mapping of 18S and 28S
      ribosomal genes of the mussel M. galloprovincialis by fluorescence in situ
      hybridization (FISH). We also apply silver staining to the same individuals in
      order to determine if structural changes are involved in the heteromorphism
      detected by this technique. Our results show that rDNA loci map on the telomeric
      region of the long arm of two submetacentric-subtelocentric chromosome pairs. In
      addition to variations in NOR expression, we found some cases of structural
      variations that affect the number of rDNA loci between individuals and the
      location of the rDNA locus between the cells of the individual. We suggest that
      FISH should be applied to other bivalves to assess the variation of rDNA loci and
      undertake more accurate interspecific comparisons.

PMID- 9760869
TI  - Geographical divergence for quantitative traits in colonising populations of
      Drosophila kikkawai from India.
AB  - There are significant geographical variations for four quantitative traits among
      eight natural populations of Drosophila kikkawai along the Indian latitudinal
      transect (8.29 to 33 degrees N). Body weight, wing length, thorax length, and
      ovariole number exhibit significant clinal variation with increase in latitutde.
      Genetic correlations between all the four traits are significantly higher. Slope
      values for body weight and wing length are higher (2.32 per degree latitude)
      while lower for thorax length (0.70) and ovariole number (0.56). South Indian
      populations are characterised by lower mean values but higher variances as well
      as CV values as compared with northern populations. Multiple regression analyses
      (on the basis of temperature related climatic variables) evidence significantly
      higher association between all the four traits and coefficient of variation of
      mean annual temperature (seasonal thermal amplitude; TCV). Thus, genetic
      differentiations for quantitative traits in D. kikkawai are due to selective
      pressure from variable seasonal environmental conditions occurring on the
      southern tropical versus northern subtropical regions of the Indian subcontinent.

PMID- 9760870
TI  - Five new cases of reciprocal translocation in the domestic pig.
AB  - Five new cases of reciprocal translocation in the domestic pig are described.
      Three of them, rep(3;5)(p1.3;q2.3), rep(6;13)(p1.5;q4.1) and
      rep(13;17)(q4.1;q1.1) were found in boars with decreased litter size. The
      remaining two were identified in animals karyotyped before reproduction: a young
      boar, rep(4;6)(q2.1;q2.8), and a gilt, rep(2;14)(q1.3;q2.7). A parental origin by
      inheritance of the translocations was established in cases 1, 4, and 5. A
      decrease in prolificacy of 43% and 34% was estimated in cases 1 and 3,
      respectively.

PMID- 9760871
TI  - An unusual translocation between 12tel and 14q11 in a large kindred.
AB  - In one couple investigated because of recurrent abortions, the female was found
      to have an unusual translocation between the long arm of the telomeric region of
      chromosome 12 and the long arm of the chromosome 14 at band q11. We studied ten
      additional members of the family who were under the risk of the same chromosomal
      rearrangement, and four of them were found to be carriers. The diagnosis of this
      translocation was determined using different banding techniques and FISH. The
      karyotype was found to be 45,XX,t(12;14)(qtel;q11).

PMID- 9760872
TI  - The phylogenetic position of Drosophila eskoi deduced from P element and Adh
      sequence data.
AB  - PCR screening with primers specific for the T-, M-, and O-type P element
      subfamilies was performed to investigate the interspecific distribution in 18
      species and to reconstruct the phylogenetic history of the various types within
      the obscura species group. T-type elements occur in D. ambigua, D. tristis, D.
      obscura, D. subsilvestris, and D. eskoi. In the genomes of D. subobscura, D.
      madeirensis, and D. guanche they are present in the form of terminally truncated
      T-type derivatives. The wide distribution suggests that the T-type subfamily had
      a long evolutionary history in the obscura lineage. In contrast, the patchy
      occurrence of M- and O-type elements can be ascribed to four independent events
      of horizontal invasion of different lineages. The cladogenesis of the obscura
      group was investigated using a partial sequence of the Adh gene as a marker. In
      contrast to earlier findings, the position of D. eskoi had to be revised. D.
      eskoi appears as the closest relative of the D. ambigua clade, whereas D.
      tsukubaensis is the sister taxon of the species pair D. bifasciata/D. imaii. This
      result is in good accordance with the P element data, where high sequence
      similarity (95%) was found among the T-type elements of D. eskoi and those of D.
      ambigua and D. tristis.

PMID- 9760873
TI  - Detailed genetic and physical mapping in the Sjogren-Larsson syndrome gene region
      in 17p11.2.
AB  - Sjogren-Larsson syndrome (SLS) is an autosomal recessive disorder characterised
      by mental retardation, spasticity, and ichthyosis. In 1994, SLS was linked to
      chromosome 17 and the gene causing the disorder was recently identified as fatty
      aldehyde dehydrogenase (FALDH) located in 17p11.2. In this paper we present a
      detailed genetic and physical map of the region surrounding the SLS/FALDH locus,
      produced by using new microsatellite markers analysed on the extensive Swedish
      family material, a radiation hybrid panel, and yeast artificial chromosomes
      (YACs).

PMID- 9760874
TI  - Comparative karyotype of pig and cattle using whole chromosome painting probes.
AB  - The extent and distribution of conserved chromosomal segments between pig and
      cattle chromosomes were established using hybridization of porcine chromosome
      painting probes on bovine metaphases. A total of 44 segments of conserved synteny
      were identified, resulting in a nearly complete coverage of the bovine karyotype.
      This study provides new data on chromosome evolution of mammals.

PMID- 9760875
TI  - Microdissection of pig chromosomes: dissection of whole chromosomes, arms and
      bands for construction of paints and libraries.
AB  - Chromosome microdissection is an important means to efficiently generate a large
      number of markers from a desired region of a genome. The present study was
      designed to initiate microdissection and amplification of DNA from whole
      chromosomes, arms, or bands of porcine chromosomes. The following pig (SSC)
      chromosomes/segments were scraped: SSC1p, SSC1q26-q2.13, SSC2q11-q14, SSC4q12
      q25, SSC13, SSC13q12-q31, SSC13q32-q43, SSC13q32-q43, SSC15, and SSC16q21-q23.
      After amplification and PCR-labelling, the DNA from the dissected segments were
      painted back to normal metaphase chromosomes to test their identity.
      Microdissection of some of the segments (on SSC4, 13 and 15) coincides with the
      mapping of economically important traits. As a first step towards generation of
      markers, microcloning of amplified product from SSC1p and SSC15 was carried out.
      The libraries were screened with a (GT)15 oligonucleotide probe. Future prospects
      of such a work in farm animals are discussed.

PMID- 9760876
TI  - Phylogenetic status of brown bears Ursus arctos of Asia: a preliminary result
      inferred from mitochondrial DNA control region sequences.

PMID- 9760877
TI  - Immortalized mouse odontoblast cell line MO6-G3 application for in vitro
      biocompatibility testing.
AB  - PURPOSE: This study was designed to determine the usefulness of an established
      stable immortalized mouse odontoblast cell line (MO6-G3) for dental material
      biocompatibility testing. Using a standard toxicity assay based on cell
      respiratory activity, the response to MO6-G3 cells was compared to the mouse
      fibroblastic cell line, L929, presently used for dental materials testing. The
      dental resin monomer TEGDMA was used as the dental material for the assay.
      MATERIALS AND METHODS: Cell lines (1 x 10(3)/well) were plated in 96 well culture
      plates and grown in DMEM supplemented with 10% FCS, 100 units/ml each of
      penicillin and streptomycin, and 50 micrograms/ml ascorbic acid in an atmosphere
      of 95% air and 5% CO2. Cells were exposed to TEGDMA resin monomer covering a dose
      range of 1 x 10(-6) to 0.5 x 10(-3) M. Unexposed control cells, as well as cells
      exposed to the DMSO vehicle in which the TEGDMA was dissolved, were included in
      all assays. Cytotoxicity was evaluated by determining cell respiratory activity
      spectrophotometrically using the tetrazolium compound WST-1. RESULTS: Statistical
      analysis by ANOVA using Tukey's method for pair wise comparisons as the post hoc
      test indicated toxic effects of TEGDMA at 1 x 10(-5) M in the odontoblast cell
      line MO6-G3. By contrast, the monomer produced no toxic effects on the L929
      fibroblast cell line after 24 hours of exposure, over the entire concentration
      range tested. Furthermore, MO6-G3 cells exposed to a concentration of 0.5 x 10(
      3) M were unable to recover from the effects of the exposure 48 hours after
      removal of the resin. MO6-G3 cells exposed to 1 x 10(-4) and 0.5 x 10(-4) TEGDMA
      recovered 40-50% and 75-80% of control respiratory activity respectively, 48
      hours after removal of the resin. Respiratory activity by L929 cells exposed to
      all TEGDMA concentrations tested was not different from the vehicle control 48
      hours after removal of the resin.

PMID- 9760878
TI  - Criteria for standardizing and increasing credibility of direct pulp capping
      studies.
AB  - There are many skeptics who condemn pulp capping but like to keep an eye on the
      research progress being made. Considerable literature emphasizes the negative
      aspects of vital pulp therapy and discourages its practice. Some clinicians and
      investigators continue to condemn pulp capping therapy for the same reasons
      reported in the literature 80 years ago despite the advances made in pulp
      biology. Clinicians are well aware of the immediate and long-term success rates
      after root canal therapy, but are less certain of the success of pulp capping. A
      number of nagging questions plague clinicians, when confronted with the choice of
      treatment. The research data on pulp capping is at times inadequate, confusing,
      misleading or even incorrect and diminishes the confidence of the practitioner in
      performing pulp capping.

PMID- 9760879
TI  - Early and intermediate time response of the dental pulp to an acid etch technique
      in vivo.
AB  - PURPOSE: To present the ultrastructural features of the pulpal responses,
      following the application of All-Bond 2 to acid-conditioned, deep, unexposed
      coronal dentin and exposed pulps in human teeth. MATERIALS AND METHODS:
      Cylindrical Class V cavities were prepared in human premolars. In the non
      exposure group an attempt was made to prepare the floor of the cavity to +/- 0.5
      mm from the pulp. In the exposure group, the pulps were intentionally exposed.
      After hemostasis, the preparation was etched with 10% phosphoric acid. The teeth
      were restored with All-Bond 2. Histological evaluation was done at 0-7, 28-35,
      and > 90 days. RESULTS: A typical connective tissue response to injury was
      observed in the majority of the specimens. Irreversible injury to the
      odontoblasts closest to the site of cavity preparations resulted in the death of
      these cells. This was followed by an early neutrophilic response, a subsequent
      macrophage response and a fibroblastic response that led to the deposition of
      either reparative dentin or calcific bridge formation by odontoblast-like cells.
      However, another notable feature was the consistent observation of resin
      particulates within the dentin-pulp complex. These resin particulates could have
      been indirectly introduced into the pulp through the pertubation of the
      junctional complexes or the death of the odontoblasts. They may also enter the
      pulp directly through a pulpal exposure. In some specimens, the presence of these
      resin particulates appeared to have triggered a foreign body response,
      characterized by the presence of a mononuclear inflammatory infiltrate as well as
      the appearance of multinuclear giant cells. The persistence of unresolved chronic
      inflammation was associated with the lack of calcific bridge formation in these
      specimens.

PMID- 9760880
TI  - The disastrous effects of the "total etch" technique in vital pulp capping in
      primates.
AB  - PURPOSE: To determine by means of a histopathological study in sub-human primates
      whether etching of an exposed pulp (the "Total Etch" technique) followed by
      capping with dentin bonding agents is a viable clinical treatment modality.
      MATERIALS AND METHODS: In six sub-human primates, 147 Class V preparations were
      made for five experimental and two control groups. After exposing the pulps, the
      preparations were intentionally contaminated, rinsed, dried and then disinfected
      with a 2% chlorhexidine solution for 60 s. In the five experimental groups, the
      entire preparation including the exposed pulp was etched with a 35% phosphoric
      acid gel, which was rinsed after 20 s. This was followed by a second application
      of chlorhexidine. In Groups 1-3, All Bond 2, ProBond and Permagen A&B dentin
      bonding agents were applied as pulp capping materials. In Group 4, a light-cured
      calcium hydroxide was tested while Group 5 was treated with a chemically-cured
      calcium hydroxide. Groups 6 and 7, the controls, were also contaminated, rinsed,
      dried and disinfected. After the exposed pulps had been protected with a
      chemically-cured calcium hydroxide (Group 6) or a light-cured calcium hydroxide
      (Group 7) the preparations were etched and restored with a bonded resin
      composite. The effect of the above described treatments were evaluated at 5, 25
      and 75 days. After sacrifice and routine histological preparation, histological
      sections were graded among other parameters for inflammatory response, bridge
      formation, maintenance of vitality, presence of dentin chips and evidence of
      microleakage microorganisms. RESULTS: The 2% chlorhexidine applied immediately
      after exposure was an effective hemostatic agent. After subsequent etching, the
      hemostatic effectiveness was greatly reduced. Exposure size for all seven groups
      ranged from 0.13-1.55 mm. The average at 5, 25 and 75 days measured 0.74, 0.66
      and 0.77 mm, respectively. In the five experimental groups, the 25- and 75-day
      groups had a total of 68 teeth of which 24 (35%) became non-vital and 23 (33%)
      teeth demonstrated bridge formation. In the three experimental groups using a
      bonding agent, the 25- and 75-day groups had a total of 40 teeth of which 18
      (45%) became non-vital and 10 (25%) exhibited bridge formation. In the "No Etch"
      control groups, the 25- and 75-day groups had 28 teeth of which two (7%) became
      non-vital and 23 (82%) exhibited bridge formation. Microorganisms were found in a
      large percentage of all groups, although their numbers were few. However, they
      were present in vital and non-vital teeth, in the presence and absence of bridge
      formation and had no direct bearing on the success or failure of the pulp capping
      procedure.

PMID- 9760881
TI  - Biocompatibility of primer, adhesive and resin composite systems on non-exposed
      and exposed pulps of non-human primate teeth.
AB  - PURPOSE: To evaluate the histologic response of 332 non-exposed and 127 exposed
      monkey pulps applying nine adhesive systems. MATERIALS AND METHODS: Class V and
      Class I cavities were used in non-exposed and exposed monkey pulps at the three
      ISO usage time intervals. RESULTS: There were no histologic differences in pulp
      responses among the nine adhesive systems used in either Class V and/or Class I
      cavities when compared to pulp responses of Ca(OH)2 controls at the ISO time
      intervals. The nine adhesive systems and resin composites are non-toxic to either
      non-exposed or exposed pulps, being biologically compatible to pulp tissues when
      placed on mechanical pulp exposures following hemorrhage control with a 2.5%
      NaOCl and per manufacturers' directions. It is imperative that clinicians
      understand the biological importance of hemorrhage control as well as the
      technique sensitivity of hydrophilic primers in order to optimize the efficacy of
      adhesives for clinical success against microleakage of bacterial factors.

PMID- 9760882
TI  - Stamp out smokeless tobacco and snuff in baseball.

PMID- 9760883
TI  - Painless dentistry. Fact or fiction?

PMID- 9760884
TI  - Mistakes. The nexus to growth and learning.
AB  - We dread mistakes because they are considered faults. The fear of making errors
      keeps us from extending ourselves professionally. We are more inclined to stay
      safe within the confines of current situations because there is comfort in its
      certainty. We tolerate less than ideal conditions because even if we are not
      prospering, we are, at least, not failing.

PMID- 9760885
TI  - A dental examination of a T-rex.

PMID- 9760886
TI  - Scuba diving dental risks.

PMID- 9760887
TI  - Piercing news.

PMID- 9760888
TI  - Coping with conflict.

PMID- 9760889
TI  - Free money for dental school.

PMID- 9760890
TI  - Understanding the biology of oral cancer and chemoprevention.

PMID- 9760891
TI  - Mouthguards reduce injuries.

PMID- 9760892
TI  - Associateships (Part 1): Landing a job.

PMID- 9760893
TI  - The Pregnancy Discrimination Act.

PMID- 9760894
TI  - A season for discontent.

PMID- 9760895
TI  - Peri-implant microflora of implants with cemented and screw retained
      suprastructures.
AB  - The aims of this study were to compare clinical and microbiological features in
      the peri-implant area of implants carrying either screw retained or cemented
      suprastructures, and to investigate the relationship between the peri-implant
      microflora, the microbiota on the inner surface of removable suprastructures, and
      the periodontal microflora within the same subject. In 15 partially edentulous
      patients with ITI implants used as abutments for crown and bridge
      reconstructions, microbial samples were taken i) from the deepest periodontal
      pocket of each quadrant, ii) from the sulcus of the implants and iii) from the
      internal surface of the screw retained suprastructures. The samples were cultured
      using continuous anaerobic techniques. Five patients were found with both screw
      retained (S) and cemented (C) suprastructures. In these subjects the mean total
      cultivable counts were significantly higher in peri-implant samples from group C
      than in samples from group S. Furthermore, peri-implant samples of group S
      yielded a higher proportion of coccoid cells in the darkfield microscope and
      demonstrated absence of large spirochetes. From the 15 patients, Porphyromas
      gingivalis was detected in 10% of the periodontal samples and in only one peri
      implant sample. Prevotella intermedia was detected in 33% of the periodontal and
      in 30% of the peri-implant samples. Fusobacterium spp. had a prevalence of 58% in
      the periodontal samples and was recovered from 50% of the peri-implant samples.
      Actinobacillus actinomycetemcomitans was not detected in any dental or peri
      implant sample. In 1 case, however, the organism was recovered from the internal
      surface of the suprastructure. Linear regression analysis showed a significant
      relationship between the frequency of micro-organisms in peri-implant samples of
      group S and in samples from the inner surface of the suprastructure. Furthermore,
      there was a significant correlation between the incidence of micro-organisms in
      dental samples and i) in peri-implant samples of group S and ii) in samples from
      the internal suprastructure surface. These findings indicate, that the microbial
      leakage through the gap between the suprastructure and the abutment plays an
      important role in the bacterial colonization of the internal part of screw
      retained crowns and bridges. The study furthermore confirms the impact of the
      dental microflora on the microbial colonization of implants. This factor appears
      to be more important than the mode of fixation of the suprastructure.

PMID- 9760896
TI  - Evaluation of postsurgical crestal bone levels adjacent to non-submerged dental
      implants.
AB  - In most of the studies on long-term radiographic evaluations of crestal bone
      levels adjacent to dental implants, no baseline radiographs taken immediately
      postsurgically had been obtained. The aim of this study was to test the
      reproducibility of a simple radiographic method for linear measurements of
      changes in bone levels and to evaluate changes in crestal bone levels adjacent to
      non-submerged ITI implants 1 year following the surgical procedure. From 128
      patients enrolled in a clinical and radiographic longitudinal study 40 patients
      also had radiographs taken immediately postsurgically. They were, however, not
      obtained as "identical" images. The radiographs were mounted onto slides and
      projected on a screen. Mesially and distally from 57 implants triplicate linear
      measurements of the distance implant shoulder to bone crest were taken, using
      known dimensions of the implants as internal reference distances. The median
      difference of 213 (out of 228 possible) duplicate measurements was 0.00 mm
      (ranging from -1.72 mm to +1.47 mm when comparing the second to the third
      reading). Some 81% of the double measurements were within +/- 0.5 mm and the
      precision was 0.30 mm. In the immediate postoperative radiographs the median
      mesial bone level was located at 2.07 mm (distally 2.19 mm) from the implant
      shoulder. A statistically significant amount of bone loss in the first year was
      observed mesially (median = -0.78 mm) and distally (-0.85 mm) (Wilcoxon matched
      pairs signed rank test P < or = 0.001). No statistically significant influence of
      the implant location, the implant length, type of the implant (screw; cylinder)
      was observed (Kruskal-Wallis P > 0.05). The age of the patients was not
      correlated significantly to the amount of bone loss observed. In conclusion,
      methodological limitations existed when evaluating linear bone changes in non
      identical radiographs using reference dimensions of the implants. The amount of
      postsurgical bone loss estimated in other studies was confirmed when using an
      immediate postoperative radiograph as a baseline.

PMID- 9760897
TI  - Five-year prospective follow-up report of the Astra Tech Dental Implant System in
      the treatment of edentulous mandibles.
AB  - This report of the 1st 2 prospective studies using the Astra Tech Implant System
      and fixed detachable bridges for rehabilitation of mandibular edentulism,
      presents clinical and radiographic data at the 5-year follow-up. The original
      material comprised 109 subjects, 56 of whom had been included in the original
      study, using the 1st generation Astra Tech Implant. Two subjects were excluded
      and the 3-year follow-up report was based on the remaining 54 subjects and 310
      fixtures. After some minor changes to the fixture and the abutment, the 2nd
      generation Astra Tech Implant was used in 53 subjects and 308 fixtures. In all 16
      subjects were lost to follow-up and the 5-year results are based on the remaining
      91 subjects with 517 fixtures in function: 5 fixtures were lost due to mobility
      at abutment installation and during the 1st year, 2 fixtures were removed due to
      pain, and after 4 years in situ 1 fixture failed. As no clinical or radiographic
      differences were obvious in the annual registrations of the 2 studies the results
      have been combined. The fixed bridges were removed at 3 and 5 years to test each
      fixture and none was mobile. The cumulative fixture survival rate at 5 years was
      98.7% and the bridge survival rate was 100%. Of the sites 82% were plaque free,
      and 96.8% showed no signs of inflammation. Over the 5-year period after bridge
      insertion, i.e. from baseline registration, there was only minor deterioration in
      marginal bone levels as measured on standardized intraoral radiographs: the mean
      differences in mm and standard deviations (SD) were -0.09 (0.27) in the 1st year,
      -0.20 (0.40) in the 3rd year, and -0.26 (0.53) in the 5th year. According to the
      stringent clinical and radiographic criteria by Albrektsson and co-workers, the
      successful treatment outcome and the survival rate in 91 subject over 5 years,
      indicates that the Astra Tech Dental Implant System with fixed detachable bridges
      is an appropriate method for rehabilitation of mandibular edentulism.

PMID- 9760898
TI  - A 2-year report on maxillary and mandibular fixed partial dentures supported by
      Astra Tech dental implants. A comparison of 2 implants with different surface
      textures.
AB  - In 50 partially edentulous patients, 133 (48 maxillary; 85 mandibular) Astra Tech
      dental implants of 2 different surface textures (machined; TiO-blasted) were
      alternately installed, supporting 52 fixed partial dentures (FPDs). Before
      abutment connection 2 machined implants (1 mandibular; 1 maxillary) were found to
      be non-osseointegrated and were replaced. Another implant could not be restored
      due to a technical complication. Two FPDs were remade because of technical
      complications, both because of abutment fractures. Thus, after 2 years in
      function, the cumulative survival rates were 97.7% and 95.7% for implants and
      prostheses, respectively. There was no statistically significant difference in
      survival rate between the 2 types of implants, 100% (TiO-blasted) vs 95.3%
      (machined), P = 0.24. After 2 years in function, when both jaw and type of
      implants were combined, the mean (SD) marginal bone loss was 0.24 (0.69) mm. No
      statistically significant difference in bone loss was found between the 2 types
      of implant after 2 years of loading, 0.04 (0.82) mm, P > 0.30.

PMID- 9760899
TI  - Inter- and intraobserver variability in radiographic bone level assessment at
      Branemark fixtures.
AB  - The aim was to determine inter- and intraobserver variability in radiographic
      bone level assessments at Branemark fixtures and to study the influence of
      various factors (radiographic density; projection geometry; jaw in which the
      fixtures were inserted; degree of bone loss; time after fixture loading; and
      number of radiographs of each fixture) on the variability. Intraoral radiographs
      from bridge connection and 1- and 3-year check-ups from 15 upper and 15 lower
      jaws (172 fixtures) were assessed by 6 observers. Measurements were taken from a
      reference point on the fixture to the marginal bone level, and some were repeated
      by all observers after 1 months. Results showed a small interobserver variation
      (0.14 mm) with the intraobserver variation (0.08 mm) as its largest component.
      The radiographic density and the degree of bone loss showed the strongest
      influence on the interobserver variation. The only variable with a significant
      effect on the intraobserver variation was the number of radiographs of each
      fixture. Calculated confidence values showed that measurement reliability can be
      improved by letting one observer or preferably more make several, independent
      readings, allowing for the demonstration of minor differences in bone height over
      time or between implant systems.

PMID- 9760900
TI  - Influence of barrier occlusiveness on guided bone augmentation. An experimental
      study in the rat.
AB  - The present study was designed to test perforated and non-perforated barriers for
      their ability to promote augmentation of bone tissue. More specifically, 1
      totally occlusive barrier and 6 barriers with perforation sizes of about 10, 25,
      50, 75, 100, and 300 microns and 1 group with no barriers placed (open test
      chambers) were used to test the effect of a barrier's occlusiveness on the amount
      and composition of augmented tissue over time. The skull of the rat was used as
      the experimental area. Prefabricated, flexible silicone frames with an inferior
      flange for peripheral sealing to the bone surface and a central vertical through
      hole with a diameter of 3.6 mm and a height of 2 mm were used as test chambers.
      The barriers were inserted to cover the superior opening of the through hole. The
      healing periods were 4, 8, and 12 weeks. All test chambers exhibited newly formed
      skull bone which was augmented over time. The placement of totally occlusive
      barriers resulted in the slowest rate of bone tissue augmentation but in a highly
      predictable manner, i.e., there were only small individual variations. Placement
      of barriers with perforations exceeding 10 microns, on the other hand, resulted
      in a faster rate of bone augmentation with larger individual variations and a
      totally different augmentation pattern. A pronounced augmentation of calvarial
      soft tissue from the sagittal suture of the skull as well as ingrowth of
      suprabony connective tissue through the barriers were also observed. After 12
      weeks of healing, no differences in the amount of augmented mineralized bone
      related to perforation sizes > 10 microns were found. The open test chambers also
      showed bone augmentation, although most of their volume was occupied by suprabony
      connective tissue.

PMID- 9760901
TI  - Bone healing capacity of titanium plasma-sprayed and hydroxylapatite-coated oral
      implants.
AB  - The influence of surface quality, in particular surface topography and implant
      material, was evaluated by inserting titanium- and hydroxylapatite plasma-sprayed
      coated implants into the maxilla of 10 goats. Three types of plasma-spray
      coatings were applied to tapered, screw shaped implants; titanium plasma-spray
      coating (TPS), titanium plasma-spray coating with additional acid passivation
      (TPSA) and a bilayered coating (TPS/HA) consisting of titanium plasma-spray
      coating (TPS) and a hydroxylapatite part (HA). In addition, as-machined implants
      (TiM) were used as control. A total of 40 implants were inserted according a
      balanced split plot design. At the end of a 3-month healing period, it appeared
      that 5 implants (2 TPS, 1 TPSA, 1 TPS/HA and 1 TiM) were lost. Histological
      examination revealed a stronger bone response to TPS/HA coated implants. Even the
      TPS/HA coated implants induced bone formation on the part of the implant inserted
      into the sinus. No signs of delamination of the TPS coatings were visible. The HA
      part of the dual coating showed signs of degradation. Histomorphometrical
      analysis confirmed these findings. A significant difference in bone contact (P <
      0.05) was measured between the TPS/HA coated implants and the other types of
      implants. Linear regression (r = 0.27) showed no correlation between the inscrew
      values at the base line and the bone contact measurements 3 months after healing.
      On the basis of these results, we can conclude that the chemical composition of
      the HA coating has a positive influence on the bone reaction. The influence of
      roughness is less evident.

PMID- 9760902
TI  - Measurements of bone and frame-work deformations induced by misfit of implant
      superstructures. A pilot study in rabbits.
AB  - This in vivo study used a 3-D photogrammetric technique to measure distortion of
      3 unit implant frame-works and bone surrounding osseointegrated implants after
      securing misfitting superstructures to the implants. Four adult loop-eared
      rabbits were provided with 3 implants each in the proximal part of 1 tibia each.
      After a healing period of 8 weeks, a titanium frame-work was connected with a
      misfit to the central implant. Three-dimensional photographs were taken before
      and after securing the central screw, which induced a calculated mean preload of
      246 N. Measurements and comparisons of the topography of the frame-works and
      surrounding bone before and after tightening the central screw indicated a
      complex and inconsistent deformation pattern. Generally, it could be observed
      that the top edge of the central cylinder showed vertical movement towards the
      bone of about 150 microns, always in combination with a rotation of the entire
      super-structure. The head of the central implant seemed to show a corresponding
      displacement towards the frame-work of about 50 to 200 microns. Bone deformation
      was found to be basically localized between the implants, where compressions of
      about half a millimetre were observed. This concentration of bone deformation as
      a result of misfit may be one contributing factor to initial marginal bone loss,
      occasionally observed after insertion of implant supported prostheses.

PMID- 9760903
TI  - Antibiotic abuse: let's stop it now.

PMID- 9760904
TI  - Practice management companies: illegally practicing dentistry?

PMID- 9760905
TI  - Latex allergy: everyone's concern.

PMID- 9760906
TI  - I-9 forms must be completed for all employees.

PMID- 9760907
TI  - To buy or to lease?

PMID- 9760908
TI  - Meet Dr. Michael Jennings new MDA President.

PMID- 9760909
TI  - Has the dental profession become a dental industry?

PMID- 9760910
TI  - Planning ahead for a secure, successful future.

PMID- 9760911
TI  - Restorative considerations: comprehensive management of the embrasure space.

PMID- 9760912
TI  - The physiologic restorative dimension.

PMID- 9760913
TI  - How well do you know your patients?

PMID- 9760914
TI  - Ethical dilemma. What would you do?

PMID- 9760915
TI  - Ethical dilemma. What would you do?

PMID- 9760916
TI  - Has competence replaced excellence?

PMID- 9760917
TI  - Buonocore Memorial Lecture. Materials of the future: preservative or restorative?

PMID- 9760918
TI  - Repairability of three resin-modified glass-ionomer restorative materials.
AB  - The purpose of this study was to evaluate the repair shear bond strengths of
      three resin-modified glass-ionomer restorative materials repaired at two
      different times. Thirty specimens of Fuji II LC, Vitremer, and Photac-Fil were
      prepared in cavities (2 mm x 7 mm) cut into acrylic resin cylinders. After the
      initial fill, half of the specimens were repaired 5 minutes later and half 1 week
      later. The specimens were stored in 37 degrees C distilled water when not being
      repaired or tested. Repairs were made without any surface preparation of the
      initial fill. Each specimen was mixed according to the manufacturer's directions,
      placed in the preparation in 1-mm increments and photocured for 40 seconds. The
      last increment was covered with a plastic strip and a glass slide before curing
      to create a smooth surface. Repairs were accomplished by drying the specimen for
      10 seconds, then adding the new material to the unprepared surface using a 3-mm
      thick polytetrafluoroethylene mold. The specimens were thermocycled 500 times,
      stored in 37 degrees C distilled water for 1 week, then loaded to failure in
      shear at a rate of 0.5 mm/min. Data were analyzed using a one-way ANOVA and Z
      value multiple comparison test to determine significant differences at the 0.05
      significance level. Vitremer showed no significant difference in shear bond
      strength for 5-minute and 1-week repair periods, while Fuji II LC and Photac-Fil
      did. Repair bond strength of Vitremer was significantly greater than Fuji II LC
      and Photac-Fil at both repair times. This study showed that time of repair
      significantly affected the bond strength of two of the materials tested.

PMID- 9760919
TI  - Repair of new-generation tooth-colored restoratives: methods of surface
      conditioning to achieve bonding.
AB  - The shear bond strength of repaired resin-modified glass-ionomer cements and
      polyacid-modified composite resins after different methods of surface
      conditioning was studied. For the resin-modified glass-ionomer cement, none of
      the surface treatment methods had a significantly higher repair bond strength
      than the control. For the polyacid-modified composite, the application of low
      viscosity resin after treatment with maleic acid, polyacrylic acid, and air
      abrasion appeared to be of paramount importance, for it enhanced bonding of the
      repaired specimens.

PMID- 9760920
TI  - Factors affecting light transmission of single-use, plastic light-curing tips.
AB  - Recently, manufacturers introduced presterilized, single-use, plastic light
      curing tips to be used either routinely or on patients with known or questionable
      communicable health concerns. The purpose of this study was to examine the effect
      of these single-use tips on light transmission compared to conventional fiber
      optic bundles in a variety of commercial light-curing units. Also, the effects of
      surface contact with the plastic tips (human tissues, reflective or opaque media,
      and barrier films) were evaluated. Where applicable, single-use tips from two
      sources (Caulk/Dentsply and Demetron) were placed in commercial curing units
      (Optilux 150 and 500, MAX 100, Spectrum Curing Light, and 3M XL-3000), and the
      intensity was compared to that of the conventional glass curing tip used with
      that specific curing unit. Intensity readings were also made for 6 continuous
      minutes using plastic tips in a high-intensity curing unit to simulate veneer
      bonding. If the sides of the plastic tip came in contact with the operator's
      fingers or the patient's tongue and/or cheek during a clinical procedure, a
      lowering of transmitted light intensity resulted. The glow emitted from the sides
      of the tip when in use may be annoying to the operator. To prevent this glare,
      the operator may be tempted to treat the sides of the tip by painting, applying a
      thin polymer barrier, abrasion, or wrapping in an opaque reflective material
      (aluminum foil). A significant decrease in light intensity can result if plastic
      curing tips contact oral tissues or bare hands. Application of thin polymer
      barriers was found to significantly reduce light transmission value. Also,
      surface modification (coating with paint or surface scratches) was found to
      greatly reduce light intensity levels, while wrapping the tip in aluminum foil
      produced a very small increase. Results indicated that transmitted light
      intensity with use of plastic tips was dependent upon both the brand of plastic
      tip tested and the different photocuring units. Either a slight increase or a
      slight decrease in intensity was noted. Plastic tips did not degrade in
      transmitted intensity when exposed to the heat produced during a simulated
      veneering scenario. In summary, use of plastic, single-use light-curing tips can
      provide adequate intensity for photoactivated restorative techniques; however,
      the clinician must be aware of specific, clinically relevant limitations with
      their use. Clinicians must also note that these tips are not designed for re-use.

PMID- 9760921
TI  - Resin-infiltrated dentin layer formation of new bonding systems.
AB  - The purpose of this study was to evaluate the resin-dentin interfacial morphology
      and shear bond strength of several new and experimental dentin bonding systems
      classified as single-bottle/total etch, multi-step/total etch, and self-etching.
      Class 1 and 5 cavities were prepared from freshly extracted permanent molars and
      restored with composite resin. Each bonded sample was cross sectioned and one
      half was completely demineralized and deproteinized, while the other half was
      polished along the cut surface to permit measurement of the thickness of resin
      infiltrated dentin layer (RIDL) within intertubular dentin (iRIDL) and around the
      peritubular walls (pRIDL) of resin tags by SEM. Shear bond strength was measured
      for all the systems 2 minutes after photocuring. SEM showed iRIDL and resin tags
      of different morphology depending on material and dentin location. The iRIDL was
      thinner in superficial dentin and thicker in deep dentin. Peritubular RIDL
      (pRIDL) was thinner than intertubular RIDL. Bond strength measurements varied
      from 12 to 21 MPa, depending on the materials used. Self-etching primer systems
      exhibited the highest bond strength, although one of the one-step/total etch
      systems also yielded very high values. The contribution of pRIDL to adhesion onto
      superficial dentin is limited by the small number of tubules. Single-component
      bonding agents produced SEM morphology and bond strengths similar to those of
      multi-step systems. Self-etching systems, despite their limited RIDL thickness,
      produced the highest immediate bond strengths. Bond strength did not correlate
      well with the thickness and morphology of RIDL.

PMID- 9760922
TI  - Bonding of amalgam and a gallium alloy to bovine dentin.
AB  - The shear bond strengths of an amalgam (Permite C) and a gallium alloy (Galloy)
      to dentin, mediated by four dentin adhesives (Super-Bond D-Liner, Super-Bond D
      Liner II, Paama 2, and Panavia 21), were investigated. Flat labial dentin
      surfaces were prepared from bovine lower incisor teeth. A 3 mm-in-diameter area
      of dentin was bonded according to each manufacturer's directions before placement
      of Permite C or Galloy. The bonds were stressed in shear at a crosshead speed of
      1 mm/min. The mean shear bond strengths were analyzed using one-way ANOVA and
      Student's t-test, and fracture modes were assessed under X20 magnification and
      analyzed using Kruskal-Wallis and Mann-Whitney U tests. Scanning electron
      micrographs were taken of the bond interface of separate samples. The results
      showed no significant difference among the bond strengths of Super-Bond D-Liner
      (2.79 MPa, 2.69 MPa), Super-Bond D-Liner II (3.41 MPa, 2.65 MPa), and Paama 2
      (0.70 MPa, 0.50 MPa) bonded to Permite C and Galloy (respective values in
      parentheses); however, Panavia gave a significantly better bond with Permite C
      (0.42 MPa) than with Galloy (0 MPa). Super-Bond D-Liner and Super-Bond D-Liner II
      gave stronger bonds than Paama 2 and Panavia with both Permite C and Galloy. For
      each dentin adhesive, there was no difference in fracture mode between Permite C
      and Galloy. It was concluded that, since all bond strengths were very low, none
      of the dentin adhesives tested would enhance the clinical retention of Permite C
      or Galloy. However, although the use of Paama 2 with Galloy was originally
      recommended by the manufacturer for dentin sealing purposes, no adhesion was
      claimed.

PMID- 9760924
TI  - Dental implantology through the millennium: a personal perspective and
      commentary.

PMID- 9760923
TI  - Intraoral repair of the fractured porcelain restoration.
AB  - Until recently, there was no predictable technique for repairing the fractured
      porcelain restoration. However, with the advent of many new products related to
      bonding porcelain, there are techniques available today to repair fractured
      porcelain with moderate expectations of success.

PMID- 9760925
TI  - The implant quality scale: a clinical assessment of the health--disease
      continuum.
AB  - Implant success is as difficult to describe as the success criteria required for
      a tooth. A range from health to disease exists in both conditions. The primary
      criteria for assessing implant quality are pain and mobility. The presence of
      either one greatly compromises the implant, and removal is usually indicated.
      Probing depths may be related to the presence of local disease or pre-existing
      tissue thickness before the implant was inserted. An increasing probing depth is
      more diagnostic and signifies bone loss, gingival hyperplasia or hypertrophy.
      Bone loss is usually evaluated best with probing rather than with radiographs.
      The most common cause of bone loss during the first few years of function are
      exaggerated factors of stress. The bleeding index is easily observed and
      indicates inflammation of the gingiva. However, implant health status is not as
      related to sulcular inflammation as would be the case for a natural tooth.
      Implant failure is easier to describe and may consist of a variety of factors.
      Any pain, vertical mobility, uncontrolled progressive bone loss, and/or
      generalized periradiolucency warrant implant removal. Implant quality factors
      were established by James and modified by Misch into an implant quality scale
      which not only assesses the implant health-disease continuum, but relates
      treatment and prognosis to the existing conditions.

PMID- 9760926
TI  - The management of acrylic occlusal appliances in implant dentistry.

PMID- 9760927
TI  - Autogenous bone grafts.

PMID- 9760928
TI  - Simplicity is always best.

PMID- 9760929
TI  - PST, the essential surgical template.
AB  - The anticipated prosthesis now dictates the placement and angulation of the
      implant, thereby improving the function and the aesthetics of the final result.
      To establish a logical continuity between the surgical phases and the planned
      prosthesis, it is essential to use a transfer device. The restorative clinician
      can request a precise position and orientation of each implant with this
      communication tool. However, it is difficult to use a conventional surgical
      template following the soft tissue reflection and during preparation of implant
      osteotomy. The proper positioning of each implant is difficult to achieve,
      especially on a completely edentulous maxilla where restorations require even
      more ideal implant placement.

PMID- 9760930
TI  - The lessons of implant dentistry.

PMID- 9760931
TI  - The Endopore implant-enhanced osseointegration with a sintered porous-surfaced
      design.
AB  - The Endopore implant provides a novel method for reliable fixation of endosseous
      dental implants within the bone. Through the use of a porous-surfaced zone formed
      by sintering Ti alloy particles of the appropriate size and under appropriate
      processing conditions to a sold Ti alloy core of desired shape (tapered truncated
      cone), an implant is now available that can be placed using a relatively simple
      surgical procedure using either surgical burs or hand osteotomes. Of even greater
      value is the suitability of this implant design for treatment of cases that
      because of minimal bone height cannot be treated routinely using other currently
      available implants. The high success rates experienced with significantly shorter
      implant lengths compared with other designs indicate the appropriateness of this
      system for difficult-to-treat cases. The Endopore system represents the next
      generation of endosseous dental implants characterized by uncomplicated and
      reliable treatment for a wider range of dentally-compromised patients. Its
      history is founded on extensive and fully-documented research at the human
      preclinical stage as well as human use experiences. The results during the past
      nine years have confirmed the high expectations that those early studies
      suggested.

PMID- 9760932
TI  - Dental mutilation in southern African history and prehistory with special
      reference to the "Cape Flats Smile".
AB  - Southern Africa has a long history of dental mutilation in the form of dental
      chipping and of intentional removal of anterior teeth. The first evidence is
      found in the skeletons of Early Iron Age populations (ca. 1500 years before
      present), but the incidence decreases in archaeological sites of more recent
      origin. In modern times, dental mutilation appears to have been limited to the
      people of the countries further north in Africa, but the one exception is the
      presence of deliberate incisor removal amongst the communities of the Western
      Cape. It is hypothesised in this paper that the modern practice in the Cape is
      associated with youthful gangs in the poorer communities, and acts as part of a
      rite of passage into adulthood. The "socio-sexual" theory, as reflected in such
      names as the "passion gap", is shown to be both wrong and insulting. The name
      "Cape Flats Smile" is recommended as a more appropriate and respectful term for
      the phenomenon.

PMID- 9760933
TI  - The treatment need of a group of senior dental students as assessed by the IOTN
      and PAR indices.
AB  - Recently the Index of Orthodontic Treatment Need (IOTN) and Peer Assessment
      Rating (PAR) were introduced in the United Kingdom as a standard for future
      epidemiological research in orthodontics. The purpose of this study was to assess
      the suitability of these indices for South African epidemiological studies and to
      evaluate the treatment need of a group of senior dental students. Examinations in
      accordance with the IOTN and PAR were performed on 206 dental students by three
      postgraduate orthodontic students. According to the Dental Health Component of
      the IOTN 54.9 per cent of the sample had no treatment need, 26.7 per cent had a
      moderate treatment need and 18.4 per cent had an urgent treatment need. 74.2 per
      cent of the students were at the no-treatment-needed end of the aesthetic scale,
      which compared poorly with the 88.5 per cent recorded by student self assessment.
      The majority of dental students in this study were not in need of orthodontic
      treatment. Certain occlusal traits common to negroids, such as bimaxillary
      protrusion, are not represented in these assessment instruments and minor
      adjustments may be needed to make the systems more applicable in these population
      groups.

PMID- 9760934
TI  - The Leaning Tower of Pisa syndrome.

PMID- 9760935
TI  - New materials and techniques for endodontic-restorative treatment of a severely
      damaged and compromised molar in one visit: a case report.

PMID- 9760936
TI  - Guidelines for a code of ethics for dental publications. Federation Dentaire
      Internationale World Dental Federation.

PMID- 9760937
TI  - The International Association of Oral Pathologists ... where oral medicine and
      oral pathology meet.

PMID- 9760938
TI  - A successful combination of conflicting approaches to diastema closure--a case
      report.
AB  - The closure of anterior maxillary diastemas can be accomplished in several ways.
      A case is reported where treatment initially consisted of the provision of
      porcelain laminate veneer restorations, with an unsatisfactory result.
      Subsequently, the restorations were reduced drastically in width and reshaped.
      The tooth widths were calculated from tables of mean measurements. The spaces
      were closed by orthodontic treatment and the original restorations were retained,
      saving the patient considerable treatment.

PMID- 9760939
TI  - Ocular complications of dental local anaesthesia.

PMID- 9760940
TI  - Combination treatment of severe fluorosis.

PMID- 9760941
TI  - A new device for the removal of crowns and bridges.

PMID- 9760942
TI  - Optimal isolation for cementation with adhesive resin cement.

PMID- 9760943
TI  - Lipoma of the floor of the mouth: report of an unusually large lesion.
AB  - Although lipomas are common, benign tumours found in any part of the body, their
      occurrence in the oral cavity is relatively rare. An unusual case of a large
      lipoma appearing on the floor of the mouth in a 77-year-old male, is presented in
      this paper. The unusual appearance in this case suggests that this tumour should
      be included as a rare possibility in the differential diagnosis of swellings in
      the floor of the mouth.

PMID- 9760945
TI  - Guidelines for Peer Review. South African Dental Association.

PMID- 9760944
TI  - Pre-floss that prosthesis.

PMID- 9760946
TI  - Dental research scientist serving in two countries.

PMID- 9760947
TI  - Funding college education for children.

PMID- 9760949
TI  - Influenza vaccine, 1998-1999.

PMID- 9760948
TI  - Two new antiplatelet drugs for angioplasty and acute coronary syndromes.

PMID- 9760950
TI  - Gliadel wafers for treatment of brain tumors.

PMID- 9760951
TI  - Lipid-modifying drugs.

PMID- 9760952
TI  - Management of patients with unstable angina in a general cardiology unit.
AB  - AIMS: To review the clinical management of patients with unstable angina and to
      relate prospectively initial risk stratification, according to the Braunwald
      criteria, to subsequent cardiovascular events. METHODS: From February to April
      1996 we performed a three month prospective review of all patients with a
      diagnosis of unstable angina admitted to the coronary care unit at Auckland
      Hospital. RESULTS: One hundred and four patients (61% male), with a mean age of
      64 years, were classified as high (58%), intermediate (41%) or low risk (1%) for
      an adverse cardiac event. Twelve (12%) patients had a documented myocardial
      infarction, of whom 11 were in the high-risk group (p = 0.038). During
      hospitalisation there was one death. Twelve (12%) patients underwent inpatient
      exercise testing, five of whom proceeded to a coronary angiogram prior to
      hospital discharge. Twenty-two (21%) unstable patients underwent inpatient
      angiography without prior exercise testing. Twenty-one (20%) patients required
      revascularisation on the same admission: percutaneous coronary angioplasty (n =
      14) or coronary artery bypass grafting (n = 7). Twelve of these 21 patients were
      in the high-risk group (p = 0.999, NS). CONCLUSION: Patients admitted with
      unstable angina had low inpatient mortality but a 12% rate of subsequent
      myocardial infarction. Braunwald low-risk unstable angina patients were not
      admitted to the coronary care unit. Braunwald high-risk patients were more likely
      to develop a subsequent myocardial infarction. Stratification of patients into
      intermediate or high-risk groups did not relate to initial medical management or
      subsequent revascularisation. Thus, while this method of risk stratification may
      predict cardiovascular events, it may be of limited clinical use in the New
      Zealand environment.

PMID- 9760953
TI  - The impact of reference pricing on clinical lipid control.
AB  - AIM: Reference pricing has recently been introduced into New Zealand in an
      attempt to curb rising pharmaceutical costs. Although budget savings may be
      significant, the resulting alteration of established drug prescriptions has the
      potential to cause harm. We undertook to assess the impact of these changes in
      patients switching from simvastatin to fluvastatin following the introduction of
      reference-based pricing in New Zealand. METHODS: The fasting lipid profiles of
      262 patients in a defined geographic region were obtained after at least six
      weeks of fluvastatin therapy. These were compared to mean lipid levels obtained
      from laboratory databases for the patients while previously receiving
      simvastatin. RESULTS: There was a significant increase in total cholesterol, LDL
      cholesterol and triglyceride levels (p < 0.01). The elevation was less pronounced
      where higher incremental doses of fluvastatin were used, although still
      significant for LDL cholesterol and total cholesterol (p < 0.01). Those receiving
      maximal therapy with fluvastatin experienced similar elevations in lipid as did
      those on lower doses. CONCLUSION: The lipid elevations seen in this audit relate
      both to the lesser potency of fluvastatin and underdosing. In this high risk
      population, significant lipid elevations may conceivably produce an excess of
      vascular events. The responsibility to the taxpayer should be weighed carefully
      against the ethical responsibility to the individual patient and the potential to
      do harm. Subtherapeutic treatment may prove more costly than all the savings from
      reference pricing.

PMID- 9760954
TI  - Non-insulin-dependent diabetes mellitus in New Zealand Maori: a relationship with
      Class I but not Class II histocompatibility locus antigens.
AB  - AIMS: To investigate the possibility of a relationship between the major
      histocompatibility complex (MHC) and non-insulin-dependent diabetes mellitus
      (NIDDM) in Maori. Such relationships have previously been shown in non-European
      races with a high incidence of NIDDM. METHODS: We performed serological Class I
      and PCR-SSP Class II HLA typing on 44 Maori with NIDDM and renal failure and
      compared the results with normal Maori. RESULTS: A strong relationship with the
      HLA-B40 groups of antigens (relative risk 5.1 chi 2 = 16.8, p < 0.001) was found;
      this was mainly attributable to HLA-B48 and HLA-B60. There was no HLA Class II
      relationship. CONCLUSION: The relationship with HLA-B40 antigens suggests that
      the MHC or other genes on chromosome 6 play a role in NIDDM in Maori.

PMID- 9760955
TI  - Practising dermatology via telemedicine.
AB  - AIM: An interactive telemedicine service has been established between Taumarunui
      Hospital and the Department of Dermatology at Waikato Hospital. The first one
      hundred dermatological consultations were reviewed to see if the consultations
      were satisfactory for medical staff and patients. METHODS: A proprietary video
      conferencing system communicating via the Integrated Systems Digital Network was
      used to conduct dermatological consultations. Data were collected regarding
      waiting time, diagnosis and follow-up arrangements. Each patient was asked to
      complete a questionnaire after the consultation. RESULTS: Of these consultations,
      83 were newly referred patients and the rest were follow-ups. The median waiting
      time for a new patient was 63 days. A variety of skin lesions (in 40 patients),
      inflammatory eruptions (31) and infections (13) were diagnosed and managed.
      Sixteen patients had to be seen at the base hospital for surgical treatment (7),
      face-to-face diagnosis (3), patch testing (3), a second opinion (2), or for
      personal reasons (1). The others were followed up locally. Savings in time and
      cost to patients were noted particularly. CONCLUSION: Only about 20% of
      consultations with new patients resulted in a further face-to-face appointment.
      The majority of patients found the telelink acceptable. The data supported the
      continuation and possible expansion of the dermatology telemedicine service.
      However, improved image quality is desirable.

PMID- 9760956
TI  - MMR immunisation coverage in Christchurch. Christchurch Immunisation Coordination
      Committee.
AB  - AIM: To measure measles-mumps-rubella (MMR) immunisation status of a birth cohort
      at 18 months of age. METHOD: All children born in Christchurch in June, July and
      August 1995 who were alive at 18 months of age (n = 999), were matched with MMR
      immunisation benefit claims. Those not listed were traced. RESULT: The final
      immunisation coverage rate was estimated at 85%. CONCLUSION: An 85% coverage rate
      at 18 months fell well short of the Immunisation 2000 target of 95% coverage by
      two years of age.

PMID- 9760957
TI  - Is confidence in immunisation declining?
AB  - There is no regular immunisation coverage information in New Zealand that is
      reliable. Immunisation benefit data do provide an indication of trends. The
      benefit data show a decline in coverage in 1997, after several years of improving
      coverage. The reasons for the decline are not known, but media reports which
      dented public and professional confidence in immunisation may have played a role.

PMID- 9760958
TI  - General practitioner funding policy: from where to whither?
AB  - Six public policy objectives relating to general practitioner (GP) funding since
      1938 have been identified. They concern national health insurance, rural GP
      shortages, care for the poor, health promotion, cost effectiveness and community
      control. Each of these objectives is examined in turn, focusing on the extent to
      which each has been met. In all cases past policies have been, at best, only
      partially successful in meeting their objectives and have required little in the
      way of dismantling prior to the introduction of new GP funding initiatives
      subsequent to 1993. Theoretical principles relating to the development of
      efficient and coherent public policy are discussed. New Zealand policy relating
      to funding of GP services has rarely conformed to such principles. There is an
      emerging consensus between social democrats and libertarians that targeted
      programmes for the poor is the equitable and efficient way to proceed. A key
      policy decision concerns the balance between planned primary care services for
      low income groups and more traditional market style arrangements for others.

PMID- 9760959
TI  - Unshackling the hospitals.

PMID- 9760961
TI  - B. Ramamurthi.

PMID- 9760962
TI  - Complete recovery from hemiplegia following excision of a giant basal ganglia
      arteriovenous malformation.
AB  - A young female harbored a large arteriovenous malformation (AVM) in the basal
      ganglia associated with marked arteriovenous shunting. The complete recovery of
      her neurological deficit subsequent to excision of the AVM illustrates the
      reversibility of such severe cerebral impairment. Large lesions in the basal
      ganglia often have been deemed inoperable. However, modern advances in
      microsurgical techniques have provided the necessary illumination, magnification,
      and instrumentation that was needed for the exposure and gentle resection of the
      lesion in our patient.

PMID- 9760963
TI  - A stereotactic approach to deep-seated central nervous system neoplasms using the
      carbon dioxide laser.
AB  - This report describes a technique in which deep-seated CNS neoplasms, the volume
      and shape of which had been determined and stereotactically localized by computer
      reconstruction of CT data, were vaporized with a carbon dioxide laser attached to
      a stereotactic frame. The clinical results with 6 patients treated by this
      technique are presented.

PMID- 9760964
TI  - Treatment of brain tumors.

PMID- 9760965
TI  - Wallenberg's syndrome caused by direct brainstem injury.
AB  - A unique case of a shotgun wound producing a lateral medullary syndrome is
      reported. Evidence indicating direct brainstem injury and not vascular injury is
      presented. The long-term complications of this type of injury are stressed.

PMID- 9760966
TI  - Traumatic transient Kluver-Bucy syndrome.
AB  - A case of transient Kluver-Bucy syndrome after a gunshot wound through the head
      is presented. We have found no other case of posttraumatic Kluver-Bucy syndrome
      described in the literature. The original criteria for the syndrome are reviewed
      and compared with findings in previously reported human cases.

PMID- 9760967
TI  - What happened?

PMID- 9760968
TI  - A comparison of results from center-median and basal thalamotomies for pain.
AB  - In a personal series of 43 patients with chronic pain treated by thalamotomy, 23
      patients had basal thalamotomy and 19 had center-median thalamotomy. Forty-nine
      procedures were performed. The best results occurred in patients with pain in the
      upper part of the body and in patients who had bilateral center-median
      thalamotomy. Bilateral center-median thalamotomy was superior to basal
      thalamotomy and had fewer side effects. Despite adverse reports, thalamotomy
      remains a useful analgesic procedure.

PMID- 9760969
TI  - Transseptal approach to the sella.

PMID- 9760970
TI  - Tethered spinal cord in association with diastematomyelia.
AB  - There is no good evidence that division of the filum terminale with simultaneous
      removal of the central spur in patients with diastematomyelia improves their
      eventual neurological status. We describe 5 patients in whom the filum was not
      divided and who were later reported upon because of lack of improvement or
      because of increasing neurological deficit. In 3 patients the division of a
      congenitally short filum terminale resulted in no improvement; in the other 2,
      symptoms were relieved following the division of adhesions at the site of
      previous surgery.

PMID- 9760971
TI  - Aggressive osteoblastoma associated with subgaleal hematoma.
AB  - A 26-year-old man with a chronic subgaleal hematoma containing calcific elements
      subsequently developed an aggressive osteoblastoma within the lesion. It is
      presumed that the osseous elements associated with the chronic process underwent
      neoplastic alteration. Such a lesion should be suspected in an individual with a
      long-standing subgaleal hematoma who reports changes occurring with respect to
      either size of the lesion or the development of tenderness.

PMID- 9760972
TI  - A fast, simple, and satisfactory method of cranioplasty.
AB  - A cranioplastic technique is described that is easy to do by making a series of
      molds and an acrylic prosthesis identical to the bone segment.

PMID- 9760973
TI  - An opportunity.

PMID- 9760974
TI  - Symptomatic leptomeningeal metastases preceding other manifestations of occult
      primary brain tumors.
AB  - Rarely, primary brain tumors may present with signs and symptoms due to diffuse
      multifocal leptomeningeal spread of tumor. These false localizing signs divert
      attention from the primary tumor, which remains relatively silent. The two
      patients reported here exemplify the confusing clinical pictures that may result.

PMID- 9760975
TI  - Aneurysms of the proximal anterior cerebral artery.

PMID- 9760976
TI  - An unusual case of penetrating head injury with excellent recovery.
AB  - We report the remarkable case of the passage of a heavy metal rod through the
      head of a 42-year-old man. The patient had an excellent outcome because of prompt
      and efficient rescue efforts combined with transport to a major neurosurgical
      trauma center. Reference is made to a somewhat similar case publicized over 130
      years ago.

PMID- 9760977
TI  - Intracranial epidermoid mimicking meningioma.
AB  - A case of an epidermoid cyst in the frontal base which showed homogeneous high
      density in noncontrast computed tomography, simulating a meningioma with
      calcification, is reported. Operative findings and histological examination
      suggested that this high density was caused by spontaneous hemorrhage into the
      cyst.

PMID- 9760978
TI  - Dermoid tumor.

PMID- 9760979
TI  - The diagnosis of sacral lesions.
AB  - Clinical courses are reviewed in 4 recent patients with sacral lesions, each of
      whom was believed on initial clinical evaluation to have symptomatic herniations
      of intervertebral discs. In each patient pain in the back tended to overshadow
      radicular symptoms, and sphincteric disturbances were not prominent. Each patient
      presented some related objective abnormality on general or neurologic
      examination. The sacral lesion was invariably visible on technically satisfactory
      plain roentgenograms of the spine and was obvious on sacral tomography.
      Conventional myelography was useful in defining communication between the lesion
      and the subarachnoid space, but otherwise typically it was only subtly and
      nonspecifically abnormal. Computerized tomography (CT) proved to be the most
      revealing radiographic technique, demonstrating bony detail as well as internal
      structure and extent of the lesion; in conjunction with metrizamide myelography,
      CT provided the most definitive anatomical study. The limited utility of
      angiography in diagnosing these lesions is discussed, as are the respective
      hazards of and indications for needle biopsy and open surgical exploration.

PMID- 9760980
TI  - Amelanotic melanoma of the lung and brain with fenestrated intrinsic tumor
      capillaries.
AB  - Tissue from an amelanotic melanoma which involved the lung and brain was studied
      by electron microscopy. Endothelial fenestrae were found in the intrinsic tumor
      capillaries at both locations, a finding which does not appear to have been
      previously reported for amelanotic melanoma. Pitfalls in the diagnosis of this
      rare tumor are discussed.

PMID- 9760981
TI  - Preoperative neurological status in predicting surgical outcome of spinal
      epidural hematomas.
AB  - The postoperative progress of 3 patients with spinal epidural hemorrhage, but
      without spinal fracture or dislocation, is presented. From the literature, 158
      cases were collected of spontaneous spinal epidural hematoma treated surgically.
      Postoperative return of motor function was noted in 95.3%, 87%, and 45.3% of the
      patients with incomplete sensorimotor, incomplete sensory but complete motor, and
      complete sensorimotor lesions, respectively. Complete sensorimotor recovery
      occurred in 41.9%, 26.1%, and 11.3% of these 3 groups of patients, respectively.
      Recovery following surgical treatment depends on the severity of neurological
      deficits before treatment. However, the absence of motor or sensorimotor
      functions preoperatively does not necessarily indicate a poor prognosis.

PMID- 9760982
TI  - Rathke's cleft cyst.
AB  - Two cases of Rathke's cleft cyst which produced symptoms of compression of the
      optic chiasm are described. The first case has been followed for five years since
      the operation. No evidence of recurrence has been noticed. The prognosis after a
      partial removal of the cyst wall seems to be good with this lesion. In the second
      case, there was clinical and laboratory evidence of hypopituitarism and the CT
      scan revealed suggestive findings to differentiate the cyst from a pituitary
      adenoma.

PMID- 9760983
TI  - Spinal Cord Injury Service in the VA.

PMID- 9760984
TI  - Introduction: the ribonuclease A superfamily.
AB  - In this multi-author issue several aspects of the ribonuclease A superfamily are
      reviewed. This superfamily can be subdivided in a number of mammalian and other
      vertebrate ribonuclease families. In the introduction chapter the titles of the
      other contributions are presented. There is little uniformity in the nomenclature
      of ribonucleases, caused in part by gene duplications, which have occurred
      independently in several mammalian lineages, and which are nice examples for
      explaining orthology and paralogy in molecular evolution.

PMID- 9760985
TI  - The contribution of noncatalytic phosphate-binding subsites to the mechanism of
      bovine pancreatic ribonuclease A.
AB  - The enzymatic catalysis of polymeric substrates such as proteins, polysaccharides
      or nucleic acids requires precise alignment between the enzyme and the substrate
      regions flanking the region occupying the active site. In the case of
      ribonucleases, enzyme-substrate binding may be directed by electrostatic
      interactions between the phosphate groups of the RNA molecule and basic amino
      acid residues on the enzyme. Specific interactions between the nitrogenated bases
      and particular amino acids in the active site or adjacent positions may also take
      place. The substrate-binding subsites of ribonuclease A have been characterized
      by structural and kinetic studies. In addition to the active site (p1), the role
      of other noncatalytic phosphate-binding subsites in the correct alignment of the
      polymeric substrate has been proposed. p2 and p0 have been described as phosphate
      binding subsites that bind the phosphate group adjacent to the 3' side and 5'
      side, respectively, of the phosphate in the active site. In both cases, basic
      amino acids (Lys-7 and Arg-10 in p2, and Lys-66 in p0) are involved in binding.
      However, these binding sites play different roles in the catalytic process of
      ribonuclease A. The electrostatic interactions in p2 are important both in
      catalysis and in the endonuclease activity of the enzyme, whilst the p0
      electrostatic interaction contributes only to binding of the RNA.

PMID- 9760986
TI  - Biochemistry of frog ribonucleases.
AB  - Frogs have unique pyrimidine base-specific RNases, with structures similar to
      those of turtle, iguana and chicken RNases. Among the four frog RNases discussed
      here, three from Rana pipiens, R. catesbeiana and R. japonica oocyte cells show
      antitumour activity, and the latter two show lectin activity towards sialic acid
      rich glycoproteins. In this review, (i) we compare their unique primary
      structures with respect to the locations of their disulphide bridges, three
      dimensional structure, base specificity and heat stability as compared with RNase
      A, and (ii) we summarize current knowledge about the mode of action of lectin and
      the antitumour activities of the three frog RNases.

PMID- 9760987
TI  - Human extracellular ribonucleases: multiplicity, molecular diversity and
      catalytic properties of the major RNase types.
AB  - Human extracellular ribonucleases (RNase), together with other members of the
      mammalian RNase A superfamily, can be classified into four different RNase
      families on the basis of their structural, catalytic and/or biological
      properties. Their occurrence and main distinctive features have been described,
      and the information available on their catalytic properties has been analysed and
      discussed in comparison with those of other animal RNases. On the basis of some
      results obtained with various single- and double-stranded polyribonucleotides, it
      has been proposed that while pancreatic-type (pt) RNases could be defined as
      single-strand/pyrimidine 'preferring' ribonucleases, mammalian nonpancreatic-type
      (npt) RNases may be referred to as single-strand/pyrimidine 'specific'
      ribonucleases. In addition, some data concerning human nptRNases may support the
      suggestion [Cuchillo et al. (1993) FEBS Lett. 333: 207-210] that the enzyme
      'ribonuclease' should be reclassified as 'transferase'.

PMID- 9760988
TI  - The eosinophil ribonucleases.
AB  - The eosinophil ribonucleases, eosinophilderived neurotoxin (EDN/RNase 2) and
      eosinophil cationic protein (ECP/RNase 3) are two closely related proteins with
      intriguing functional and evolutionary properties. While both EDN and ECP
      maintain the structural and catalytic residues typical of the RNase A
      superfamily, the role of ribonuclease activity in the physiologic function of
      these proteins remains unclear. The biochemistry and physiology of EDN, ECP and
      the recently discovered ribonuclease k6 (RNase 6) will be reviewed in this
      chapter.

PMID- 9760989
TI  - Ribonuclease 4, an evolutionarily highly conserved member of the superfamily.
AB  - The structural and enzymatic properties of RNase 4 are reviewed. This RNase shows
      a much higher interspecies similarity (approximately 90%) than the other members
      of the RNase A superfamily. The enzyme is ubiquitous, with the highest amounts
      present in liver and lung. Its unique uridine specificity results from
      alterations in and around the pyrimidine-binding site. In particular, the
      shortened C-terminus and the side chains of Phe-42, Asp-80 and Arg-101 appear to
      be involved. RNase 4 binds tightly to the intracellular RNase inhibitor, with a
      Kd of 4 x 10(-15) M.

PMID- 9760990
TI  - The angiogenins.
AB  - The angiogenic and other biological functions of the angiogenins, members of the
      pancreatic RNase superfamily of proteins, are reviewed in the context of their
      primary and tertiary structures. The ribonucleolytic activity and interactions
      with the placental ribonuclease inhibitor have seen much study in the last few
      years. The mechanism of the angiogenic activity of angiogenin has recently been
      postulated as involving multiple interactions with other proteins through
      specific regions on the molecular surface of angiogenin. These molecular partners
      include heparin, plasminogen, elastase, angiostatin, actin and most importantly a
      170-kilodalton receptor on subconfluent endothelial cells. The existence of the
      latter receptor was established in conjunction with a mitogenic activity of
      angiogenin on subconfluent cells. The levels of angiogenin in various
      physiological and disease states are summarized, including various studies on
      pregnancy and angiogenin. Correlations are seen between states of enhanced
      angiogenesis and angiogenin levels. An overview of the relationship of angiogenin
      and the other RNases of the superfamily showed that their genes all are in
      relative close proximity on human chromosome 14. Examination of the many
      expressed sequence tags published in the public databanks, for angiogenin and the
      other RNases, revealed that angiogenin and RNase-4 (the most evolutionarily
      conserved RNase), share various identical 5'-untranslated regions on their sets
      of messenger RNAs, suggesting that their genes are in very close proximity on
      chromosome 14 and that they are products of differential splicing. This in turn
      suggests that, in both humans and mice, expression of these two proteins is under
      identical control, with obvious implications for their biological activities. The
      evolutionary history of the angiogenins is examined briefly on the basis of the
      protein sequences of the human, rabbit, pig, two bovine and four mouse
      angiogenins, and two mouse angiogenin pseudogene sequences. The discrepancy
      between the conventional requirement for conservatism in structure to allow
      multimolecule interactions, and the actual fast-changing sequence of the
      angiogenins, in concert with the wide-ranging activity even in birds, of human
      angiogenin, is discussed.

PMID- 9760991
TI  - The ribonuclease A superfamily: general discussion.
AB  - Enzymic properties of members of the ribonuclease A superfamily, like the
      activity on RNA, the preference for either cytosine or uracil in the primary
      binding site B1, the preference for the other side of the cleaved phosphodiester
      bond, the B2 site, and features of the two noncatalytic phosphate-binding sites
      P0 and P2 are discussed in several articles in this multi-author review, and are
      summarized in this closing article. A special feature of members of the
      ribonucleases 1 family is their destabilizing action on double-stranded nucleic
      acid structures. A feature of the ribonuclease A superfamily is the frequent
      occurrence of gene duplications, both in ancestral vertebrate lineages and in
      recently evolved taxa. Three different bovine ribonucleases 1 have been
      identified in pancreas, semen and brain, respectively, which are the result of
      two gene duplications in an ancestral ruminant. Similar gene duplications have
      been identified in other ribonuclease families in several mammalian and other
      vertebrate taxa. The ribonuclease family, of which the human members have been
      assigned numbers 2, 3 and 6, underwent a still mysterious pattern of gene
      duplications and functional expression as proteins with ribonuclease activity and
      other physiological properties.

PMID- 9760992
TI  - Bacterial nonspecific acid phosphohydrolases: physiology, evolution and use as
      tools in microbial biotechnology.
AB  - Bacterial nonspecific acid phosphohydrolases (NSAPs) are secreted enzymes,
      produced as soluble periplasmic proteins or as membrane-bound lipoproteins, that
      are usually able to dephosphorylate a broad array of structurally unrelated
      substrates and exhibit optimal catalytic activity at acidic to neutral pH values.
      Bacterial NSAPs are monomeric or oligomeric proteins containing polypeptide
      components with an M(r) of 25-30 kDa. On the basis of amino acid sequence
      relatedness, three different molecular families of NSAPs can be distinguished,
      indicated as molecular class A, B and C, respectively. Members of each class
      share some common biophysical and functional features, but may also exhibit
      functional differences. NSAPs have been detected in several microbial taxa, and
      enzymes of different classes can be produced by the same bacterial species.
      Structural and phyletic relationships exist among the various bacterial NSAPs and
      some other bacterial and eucaryotic phosphohydrolases. Current knowledge on
      bacterial NSAPs is reviewed, together with analytical tools that may be useful
      for their characterization. An overview is also presented concerning the use of
      bacterial NSAPs in biotechnology.

PMID- 9760993
TI  - The effect of monensin and chloroquine on the endocytosis and toxicity of
      chimeric toxins.
AB  - The toxicity of two conjugates containing ribosome-inactivating proteins (RIPs,
      i.e. saporin and ricin-A chain x-linked to transferrin) has been measured on a
      prostatic cancer line (PC3) naturally overexpressing the transferrin receptor, in
      the presence of monensin and chloroquine. This paper investigates whether the
      increased toxicity of Tf-RIPs induced by monensin and chloroquine may be due to
      alterations of the normal endocytotic pathway of the complexes mediated by the
      transferrin receptor. Monensin, besides inducing alkalinization of normally acid
      intracellular compartments, causes an accumulation of the receptor-bound Tf-RIP
      in a perinuclear region contiguous to the cisternae of the trans-Golgi network.
      Chloroquine, though increasing the intracellular pH, seems not to modify the
      endocytotic pathway of these chimeric molecules. We believe that the enhanced
      toxicity of the Tf-RIPs may be related to intracellular alkalinization (i.e.,
      endosomal or lysosomal pH) rather than to the effects on the recycling of
      transferrin receptor-bound toxins. We conclude that the efficacy of chimeric
      toxins may be modulated not only by the carrier used for their engineering but
      also by addition of drugs able to influence the stability and activation of the
      toxins inside the cell.

PMID- 9760994
TI  - The V(D)J recombination activating protein RAG2 consists of a six-bladed
      propeller and a PHD fingerlike domain, as revealed by sequence analysis.
AB  - The RAG1 and RAG2 proteins play a crucial role in V(D)J recombination by
      cooperating to make specific double-stranded DNA breaks at a pair of
      recombination signal sequences (RSSs). However, the exact function they perform
      has heretofore remained elusive. Using a combination of sensitive methods of
      sequence analysis, we show here that the active core region of the RAG2 protein,
      confined to the first three quarters of its sequence, is in fact composed of a
      six-fold repeat of a 50-residue motif which is related to the kelch/mipp motif.
      This motif, which forms a four-stranded twisted antiparallel beta sheet, is
      arranged in a circular formation like blades of a propeller or turbine. Given the
      known properties of the beta-propeller fold in mediating protein-protein
      interactions, it is proposed that this six-laded propeller structure of the RAG2
      active core would play a crucial role in the tight complex formed by the RAG1 and
      RAG2 proteins and RSSs. Moreover, the presence of a plant homeodomain finger-like
      motif in the last quarter of the RAG2 sequence suggests a potential interaction
      of this domain with chromatin components.

PMID- 9760995
TI  - Genetics of the febrile seizure susceptibility trait.
AB  - Febrile seizures are the commonest form of convulsion, occurring in 2-5% of
      infants in Europe and North America and 6-9% of infants in Japan. In large
      families, the febrile seizure susceptibility trait is inherited by the autosomal
      dominant pattern with reduced penetrance. In the other families, inheritance
      appears to be multifactorial. Recent linkage studies provide evidence that
      regions of chromosomes 8 and 19 contain febrile convulsions (FC) susceptibility
      genes. This opens up the way to cloning a febrile seizure gene and determining
      the contributions of these gene loci to febrile seizures in the sporadic cases
      and the small families. Cloning a febrile seizure gene will make possible new
      approaches to prevention and therapy. It will also be possible to determine
      whether a febrile seizure gene contributes to other types of seizures.

PMID- 9760996
TI  - Advances in pediatric neuroimaging.
AB  - Magnetic resonance evaluation of the pediatric central nervous system is rapidly
      improving in a number of ways: (1) anatomically with higher resolution; (2) with
      greater sensitivity to pathological processes characterized by increased water
      content utilizing fluid attenuated inversion recovery imaging (FLAIR); (3) with
      greater speed of acquisition with ultrafast (1 s/image) and echo planar imaging
      techniques (50 ms/image); (4) with measurement of cerebral blood flow as
      perfusion; (5) with measurement of water proton dispersion (e.g. diffusion
      imaging); (6) with measurement of biochemical components within tissues with
      proton spectroscopy; and (7) with evaluation of cortical activation with
      functional magnetic resonance imaging.

PMID- 9760997
TI  - Neuronal intranuclear inclusion disease: neuropathologic study of a case.
AB  - We report neuropathological findings in a 22-year-old man affected with neuronal
      intranuclear inclusion disease. The inclusions affected to different extents the
      various structures of the central nervous system, being more numerous in cerebral
      cortex, inferior olives, hypoglossal and oculomotor nuclei. They
      ultrastructurally differed from Marinesco bodies. In the neurons of the
      substantia nigra, we occasionally observed intranuclear inclusions resembling the
      so-called rodlets of Roncoroni. We did not observe inclusions in the
      extraneuronal tissues. There was no apparent correlation between frequency of the
      inclusions and neuronal loss. Intranuclear inclusions were found in many
      morphologically normal neurons. We suggest that the intranuclear inclusions are
      the marker of a distinctive disorder, even though their role in neuronal
      degeneration remains to be clarified.

PMID- 9760998
TI  - Fluoro-2-deoxyglucose (18FDG) PET scan of the brain in glutaric aciduria type 1:
      clinical and MRI correlations.
AB  - The clinical, PET (positron emission tomography) and MRI (magnetic resonance
      imaging) findings of brain studies in eight patients, previously diagnosed to
      have glutaric aciduria type 1, were retrospectively reviewed. The neurological
      findings typically consisted of variable degrees of dementia and extrapyramidal
      symptoms (dystonia, choreoathetosis and rigidity). Both MRI and PET showed
      involvement of the putamina in all the patients. The PET scan demonstrated
      lesions in the head of the caudate nuclei in all of the patients. Brain atrophy,
      and in particular the characteristically-enlarged Sylvian fissures, was better
      demonstrated by MRI. On the other hand, the cerebral cortex and thalamic
      structures were found to be normal by MRI in all patients, whereas PET scan
      showed decreased uptake in the cerebral cortex in seven, and in the thalami in
      three patients. Correlation between imaging and clinical findings was found to be
      good when both PET scan and MRI findings of the brain were taken into
      consideration. Therefore, the functional (PET) and structural (MRI) studies of
      the brain were complementary in the imaging evaluation of glutaric aciduria type
      1.

PMID- 9760999
TI  - Increased expression of beta-hexosaminidase alpha chain in cultured skin
      fibroblasts from patients with carbohydrate-deficient glycoprotein syndrome type
      I.
AB  - Carbohydrate-deficient glycoprotein (CDG) syndrome type I is an autosomal
      recessive multisystem disorder characterized by multiple serum glycoproteins with
      deficient oligosaccharide chains. This characteristic under-glycosylation is
      found in several serum glycoproteins. We studied secreted forms of lysosomal
      enzymes, beta-hexosaminidase and alpha-fucosidase, in serum from the patients and
      media of cultured fibroblasts. Both beta-hexosaminidase and alpha-fucosidase
      activities were increased in sera from three CDG patients. The enzyme activity
      staining using the fluorogenic substrate-4-methylumbelliferyl-alpha-L
      fucopyranoside after polyacrylamide gel isoelectric focusing revealed abnormal
      cathodal bands in sera from CDG patients. On the other hand, no abnormal secreted
      forms of beta-hexosaminidase and alpha-fucosidase were detected in media from
      cultured CDG fibroblasts by isoelectric focusing and sodium-dodecyl sulfate
      polyacrylamide gel electrophoresis. However, SDS-polyacrylamide gel
      electrophoresis and Western blotting analysis of beta-hexosaminidase using anti
      beta-hexosaminidase A (anti-alpha + beta chains) antibody, showed an increase of
      a 55-kDa mature form of the alpha chain. Northern blotting analysis identified an
      increase in mRNA levels of beta-hexosaminidase alpha chain in CDG fibroblasts.
      Although under-glycosylated fractions of these lysosomal enzymes were not
      detected in cultured fibroblasts, it was suggested that intracellular processing
      of these lysosomal enzymes in CDG patients might be altered.

PMID- 9761000
TI  - Using postural reactions as a screening test to identify high-risk infants for
      cerebral palsy: a prospective study.
AB  - To clarify the predictive value of the seven more commonly used postural
      reactions (PR) in the 1st year of life regarding the diagnosis of cerebral palsy
      (CP), we prospectively examined 204 high-risk infants of whom 58 developed CP, 22
      had developmental retardation (DR) and 124 were normal at follow-up at 3 years of
      age. Abnormalities of five or more PR from the 1st month of life were correlated
      with spastic CP, while five or six abnormal PR were also correlated with athetoid
      CP. Three or less abnormal PR correlated with a normal outcome. All seven PR
      tested were significantly abnormal in children with spastic CP from the 1st month
      compared to normal children. Athetoid children demonstrated abnormalities of the
      Peiper-Isbert (P-I) reaction and Vojta reaction from the 1st month and of the
      vertical, horizontal and Collis vertical suspension from the 3rd month. Children
      with DR had significantly abnormal Collis horizontal and Collis vertical
      suspension, Vojta reaction and traction response from the 1st month and Peiper
      Isbert reaction from the 3rd month. Ataxic children demonstrated significantly
      abnormal traction response from the 1st month, Collis horizontal reaction from
      the 7th month and Peiper-Isbert reaction from the 11th month. We conclude that
      the examination of PR is a useful quantitative and qualitative diagnostic
      screening tool for high-risk infants from the 1st month of life.

PMID- 9761001
TI  - Adrenocorticotropic hormone therapy for infantile spasms alters pyruvate
      metabolism in the central nervous system.
AB  - To clarify the mechanism of action of adrenocorticotropic hormone (ACTH) in
      treating infantile spasms, we evaluated the effects of ACTH on the metabolism of
      pyruvate in the central nervous system (CNS) of children with infantile spasms.
      We measured the levels of lactate and pyruvate in cerebrospinal fluid (CSF) and
      serum, before and during ACTH treatment in 12 children with infantile spasms. We
      evaluated statistically any correlation between the observed metabolic changes
      and the clinical response of ACTH. ACTH therapy significantly elevated the levels
      of lactate and pyruvate in the CSF and serum. The effect was not dose-dependent.
      During ACTH therapy, the serum levels of lactate and pyruvate and the ratio of
      lactate to pyruvate (L:P ratio) were unrelated to these levels in CSF. Patients
      who showed a good initial response to treatment had a significantly higher CSF
      level of pyruvate and a lower L:P ratio during therapy than did those with a poor
      initial response. This is the first report that ACTH therapy administered for
      infantile spasms alters pyruvate metabolism in the CNS. This metabolic change may
      be involved in part in the action of ACTH in relieving infantile spasms.

PMID- 9761002
TI  - Subdural hygroma in association with middle fossa arachnoid cyst: acetazolamide
      therapy.
AB  - Intracranial arachnoid cysts are cerebrospinal fluid-filled collections between
      arachnoid layers. While many are silent, arachnoid cysts can become symptomatic
      if there is sudden expansion, haemorrhage or rupture with the development of
      subdural hygroma or subdural hematoma. Several studies have demonstrated the
      association of arachnoid cysts with subdural hygroma and subdural hematoma. We
      describe a 9-year-old girl with a moderate-sized middle-fossa arachnoid cyst and
      bilateral frontal subdural hygroma presenting with raised intracranial pressure.
      She was treated with acetazolamide which resulted in resolution of the subdural
      hygroma and relief of symptomatology.

PMID- 9761003
TI  - Workshop on Autonomic Function in Rett Syndrome. Swedish Rett Center Froson,
      Sweden, May 1998.

PMID- 9761004
TI  - The influence of inhaled corticosteroids on bone mineral density in asthmatic
      children.

PMID- 9761005
TI  - Asthma and atopy in Western and Eastern communities--current status and open
      questions.

PMID- 9761006
TI  - A safe, simple, standardized method should be used for sputum induction for
      research purposes.

PMID- 9761007
TI  - The COX-1/COX-2 balance in asthma.

PMID- 9761008
TI  - Molecular mechanisms of leukotriene synthesis: the changing paradigm.

PMID- 9761009
TI  - Bone mineral density and body composition in patients with airflow obstruction-
      the role of inhaled steroid therapy, disease and lifestyle.
AB  - BACKGROUND: Inhaled steroid therapy has been shown to be associated with low bone
      mineral density (BMD) in asthmatic patients, but its effect in men has not been
      specifically studied; and the relative importance of therapy, disease and
      lifestyle leading to low BMD has not been investigated. OBJECTIVES: The study was
      designed to compare BMD in women and men who had airflow obstruction (asthma or
      COAD with or without inhaled steroid therapy) with normal controls. The role of
      inhaled steroid treatment, disease severity and lifestyle was studied among
      patients. METHODS: One hundred and fourty-four patients (106 on inhaled steroids
      and 38 not on inhaled steroids) and 212 age-matched controls were studied. Body
      composition and BMD (at the total body, hip and spine) were measured by dual-X
      ray densitometry (DEXA). Forced expiratory volume (FEV1) was measured in
      patients. A validated questionnaire was administered to measure lifestyle
      factors. RESULTS: The body mass indices (BMI) (P < 0.001) and percentage of body
      fat (P < 0.001) were higher among female patients on inhaled steroids than
      controls. However, the BMD of the total body (P < 0.05) and spine (P < 0.001)
      were significantly lower in premenopausal and postmenopausal women than controls,
      respectively (P < 0.005). The BMD at the spine (P<0.01) and hip (P < 0.01) in
      male patients were significantly lower than the controls. By multiple regression,
      age and use of inhaled steroid was negatively associated with BMD at the hip (P <
      0.01), but not at the spine (P>0.05). Cigarette smoking was associated with
      significantly lower BMD at the femoral neck (P < 0.05), and a low dietary calcium
      intake was associated with lower BMD at the spine (P<0.05). In women, use of
      inhaled steroid was not associated with significantly lower BMD. CONCLUSION: Men
      who had asthma and/or COAD had lower BMD, and this was not attributable entirely
      to steroid use. Cigarette smoking and a low dietary calcium intake may partially
      account for this difference. The difference in BMD between female patients and
      controls, even in those taking inhaled steroid, was small.

PMID- 9761010
TI  - Atopy and allergic disorders among adults in Tartu, Estonia compared with
      Uppsala, Sweden.
AB  - BACKGROUND: Recent studies in children and adults indicate that the prevalence of
      atopy and allergic disorders is lower in previously socialist countries in
      Eastern Europe compared with countries with a market economy while revealed risk
      factors are similar. OBJECTIVES: To estimate the prevalence of atopy among adults
      in Tartu, Estonia and to compare the prevalence of risk factors for atopy and
      allergic respiratory diseases in Estonia and Sweden. METHODS: As a part of cross
      sectional study-European Community Respiratory Health Survey-random samples of 20
      44 year olds (n = 351 in Tartu and n = 470 in Uppsala) and persons of the same
      age with asthma like symptoms or on current asthma medication according to a
      postal questionnaire (n = 95 in Tartu and n = 201 in Uppsala) were interviewed
      and circulating IgE antibodies were measured. RESULTS: The prevalence of atopy
      was 19% in Tartu and 32% in Uppsala (P < 0.001). The prevalence of sensitization
      to pollen was twice lower (11.5 vs 23.2; P<0.001) and the prevalence of pollen
      associated asthma symptoms was four times lower (1.7 vs 6.8; P<0.001) in Tartu
      than in Uppsala while sensitization to pollen was an equally large risk factor
      for asthma in both centres. Age was inversely related to cat and pollen
      associated symptoms of rhinoconjunctivitis in Uppsala (OR 0.6 and 0.7,
      respectively, P < 0.05) but not in Tartu. CONCLUSIONS: The prevalence of atopy
      was lower in Tartu, Estonia than in Uppsala Sweden. Perception of allergic
      disorders seemed to be lower in Tartu than in Uppsala. Age did not influence the
      prevalence of atopy nor allergic disorders in Tartu, while in Uppsala age was
      inversely related to clinical allergy. This could suggest a cohort effect
      underlying the increasing prevalence of allergy in Western Europe.

PMID- 9761011
TI  - Induced sputum eosinophil cationic protein (ECP) measurement in asthma and
      chronic obstructive airway disease (COAD)
AB  - BACKGROUND: Induced sputum is a useful way to monitor airway inflammation in
      asthma, but cell counts are time-consuming and labour intensive. OBJECTIVE: The
      aim of this study was to evaluate a novel processing method using eosinophil
      cationic protein (ECP) as a biochemical marker of sputum eosinophil number and
      activation in subjects with asthma and other airway diseases. METHODS: Sputum was
      dispersed with dithiothreitol and centrifuged to yield cell free supernatant and
      a cell pellet. The pellet was treated with a cellular lysis buffer to release
      cell-associated ECP. ECP was measured in sputum supernatant and in the lysed cell
      pellet and was compared with sputum eosinophil counts in 31 adults with asthma,
      chronic obstructive airway disease (COAD), bronchiectasis and healthy controls.
      The ratio of supernatant to pellet ECP was evaluated as an index of eosinophil
      degranulation. The effect of sputum processing reagents and storage time on ECP
      measurement was also evaluated. RESULTS: ECP measured in the cell pellet lysate
      correlated closely with sputum absolute eosinophil counts across a range of
      subject groups (r = 0.72, P = 0.004). Sputum eosinophil counts were less well
      correlated with supernatant ECP levels (r = 0.54, P < 0.05). Incubation with
      dithiothreitol or lysis buffer did not influence ECP measurement and sputum ECP
      levels were stable over a 6-9 month period. Sputum supernatant and pellet lysate
      ECP concentrations were increased in stable asthma, asthma exacerbations and
      COAD/bronchiectasis (P < 0.05). The ratio of supernatant to pellet ECP was used
      as an index of eosinophil degranulation and found to be elevated in asthma
      exacerbations, COAD and bronchiectasis, but not in stable asthma. CONCLUSION: The
      measurement of ECP in the sputum cell pellet provides a reliable and efficient
      estimate of sputum eosinophil counts which can potentially be used in clinical
      trials and epidemiological surveys. The ECP ratio may be a useful marker of
      eosinophil activation, and was increased in asthma exacerbation and COAD. The
      increased ECP in COAD reflects a non-selective accumulation of eosinophils in
      this condition.

PMID- 9761012
TI  - Asthma, rhinitis and eczema in Maltese 13-15 year-old schoolchildren --
      prevalence, severity and associated factors [ISAAC]. International Study of
      Asthma and Allergies in Childhood.
AB  - BACKGROUND: Allergic conditions, especially asthma, seem to be increasingly
      common the world over. The International Study of Asthma and Allergies in
      Childhood [ISAAC] was the first worldwide study carried out with standardized
      questionnaires in order to create a reliable global map of childhood allergy.
      OBJECTIVES: The Maltese Islands were one of the centres participating in this
      study and in this paper the data obtained from 4184 13-15 year olds from 22 state
      and three private schools [88.7% response rate], and also data obtained from some
      added 'local' questions addressed to the same children, are included. in order to
      evaluate the problem of allergic conditions in Maltese schoolchildren. RESULTS:
      27.9% of the participants were wheezers 'ever' while 16% were current wheezers.
      Of the latter children 15.1% were experiencing nocturnal wheezing at least once a
      week and 22% had a wheezing episode severe enough to limit speech. Nasal problems
      were present in 52.7% of these teenagers and 47.4% of all respondents persisted
      with these symptoms up to the year of answering the questionnaire. Hayfever had
      been diagnosed in 32.3% of all the children. 12.8% of respondents had a recurring
      itchy rash suggestive of eczema for at least 6 months of their lives and 10% had
      it currently. This was slightly lower than the global mean, unlike the case of
      wheezing, which in Malta was more common than the world average, and rhinitis,
      for which we had the second highest cumulative prevalence rate in the world.
      Multiple variables such as gender, smoking, family history of atopy, pets, soft
      furnishings and living in busy roads affected the prevalence and severity of the
      allergic conditions studied. CONCLUSIONS: Allergic conditions are very common in
      Maltese schoolchildren and are causing a lot of hardship to these same
      youngsters. The results of this study should serve as a stimulus to try and
      decrease this suffering through better management of these conditions, measures
      to control possible detrimental factors and further research on asthma, allergic
      rhinitis and eczema.

PMID- 9761013
TI  - Dermatophagoides sp. and IgE anti-D. pteronyssinus and D. farinae detection in a
      Venezuelan community at more than 2000 m above the sea level.
AB  - BACKGROUND: It has been reported that the concentration of Dermatophagoides sp.
      population, the main trigger of asthma in sensitized atopic subjects, is
      inversely related with altitude and probably directly with humidity and that this
      population are scarcely found over 1750 m above sea level. OBJECTIVE: We studied
      the presence of Dermatophagoides sp. in a Venezuelan community between 2040 and
      2600 m above sea level, and also the IgE response to D. pteronnyssinus and D.
      farinae in atopic subjects living on that region. METHODS: The presence of
      Dermatophagoides sp. was determined by microscopic identification of mites in
      dust, obtained by brushing the mattresses surface in 93 randomly selected houses
      between 2040 and 2600 m above sea level. The indoor relative humidity was also
      measured. The specific IgE serum levels were studied in 65 subjects classified as
      asthmatics, allergic non-asthmatics and non-allergic. RESULTS: A mean
      concentration of 188 mites/g of room dust was determined in 82.4% of houses with
      an indoor relative humidity ranging from 89% and 92% independently of altitude.
      The density of Dermatophagoides sp. was sufficiently high to sensitize the atopic
      subjects, IgE levels were 6.8 PRU mean value for asthmatic, against 0.38 PRU in
      non-atopic. CONCLUSIONS: We conclude that: (a) Dermatophagoides sp. can be found
      up to 2600 m above sea level in a Venezuelan neotropical region where a high
      indoor relative humidity is characteristic of most dwellings; (b) sensitization
      by D. pteronyssinus and D. farinae were demonstrated in atopic subjects resident
      at that region.

PMID- 9761014
TI  - Direct measurements of temperature and humidity in dust mite microhabitats.
AB  - BACKGROUND: Up to 70% of atopic asthmatics have a positive skin test to the dust
      mite allergen Der p 1. Reduction of dust mite numbers by lowering room humidity
      control is one suggested technique for reducing dust mite allergen levels to
      clinically acceptable levels. Trials of this technique in temperate climates have
      reported mixed results. It has been speculated that one reason for this is that
      humidity changes in room ambient air are not tightly linked to humidity changes
      in the dust mite microenvironment (in the base of carpets, bedding, furniture
      etc.). OBJECTIVE: To directly measure humidities and temperatures in dust mite
      microenvironments and compare these to ambient conditions, and so gather data on
      how the microclimates are influenced by room conditions and moisture and heat
      sources, such as an occupant in a bed. METHODS: A special small humidity device
      has been developed which can discriminate humidity changes over distances of
      millimetres. With these devices microclimates have been measured in the base of
      carpets, in layers through bedding, and in furniture. RESULTS: Measured base-of
      carpet humidities were significantly higher than room humidities. Bedding
      relative humidities show complex behaviour according to the distance separation
      between the measuring point and the occupant. Immediately below the occupant, bed
      relative humidities fall when the person enters the bed. Similar behaviour is
      observed in a sofa. CONCLUSION: Some dust mite microclimates have been shown to
      be very different from room conditions. Consequently, reduction of dust mite
      numbers and allergen levels cannot be guaranteed by the controlling of room
      humidities.

PMID- 9761015
TI  - Food allergy to peanuts in France--evaluation of 142 observations.
AB  - BACKGROUND: The increase in frequency of peanut allergy and fatal cases have been
      reported. OBJECTIVES: The objective of this study is to document the severity of
      food allergy to peanuts by evaluating the reactive dose of peanuts and to search
      for the role of peanut oil. METHODS: This study is carried out on the basis of
      142 observations collected according to the same diagnostic methodology in two
      allergy centres in France. Skin-prick-tests were performed with peanut powder,
      peanut oil and peanut oil proteinic extract. Labial provocation tests were
      performed on 121 patients. The reactive dose of peanuts and the role of peanut
      oil were determined by standardized oral provocation tests in 50 and 62 patients
      respectively. The data are computerized and the data bank includes 509 food
      allergic patients. RESULTS: Allergy to peanuts represents 28% of food allergies
      and occurs under 1 year of age in 46% of cases, under 15 years of age in 93%. The
      clinical features were atopic dermatitis (40%), angioedema (37%), asthma (14%),
      anaphylactic shock (6%) and digestive symptoms (1.4%). The specific IgE were
      class 3 or higher in 80% of cases. The total reactive dose was less than 100 mg
      in 25% of cases, from 100 mg to 1 g in 62.5%. All patients reacted to a dose of
      less than 7.1 g. The threshold of peanut reactivity was lower than the threshold
      of egg reactivity. An allergy to peanut oil was demonstrated in 14 patients.
      CONCLUSION: The severity of peanut allergy and the early onset of the occurrence
      of this allergy is documented. The role of residual allergenic proteins in peanut
      oil is established by positive skin-prick tests to proteic extracts from peanut
      oil and by double-blind placebo-controlled challenges to peanut oil. The
      increased consumption of allergens in the form of peanut oil and fats can
      contribute to the occurrence or persistence of symptoms and may be suspected to
      increase the risk of sensitisation.

PMID- 9761016
TI  - Correlation between antigen-specific IL-2 response test and provocation test for
      egg allergy in atopic dermatitis.
AB  - BACKGROUND: The antigen-specific interleukin-2 response (AIR) test using
      lymphocytes is effective in searching for the antigen which causes allergic
      diseases and understanding their disease activity. OBJECTIVE AND METHODS: The
      correlation between the raw egg oral provocation test and egg white antigen
      specific interleukin-2 (IL-2) response test was investigated in 123 children with
      infantile atopic dermatitis and 13 children with bronchial asthma. RESULTS: Among
      the 83 who showed positive reactions to provocation, 75 also reacted positively
      to the AIR test (sensitivity, 90.4%), while among the 53 children who showed
      negative responses to antigen provocation, 45 produced negative responses to the
      AIR test (specificity, 84.9%). The specificity of egg white IgE RAST score and
      skin-prick test are 88.7 and 81.3% which are comparable to that of the AIR test.
      However, their sensitivity was low (38.6 and 66.7%). In the patterns of symptom
      developed in the provocation AIR displayed late and delayed type allergic
      responses in addition to the immediate type which RAST reflected. The RAST
      negative group composed of 98 patients included 51 (52.0%) who exhibited positive
      reactions to the provocation test. Among these 44 responded positively to the AIR
      test (86.3%). CONCLUSION: The AIR test is effective for screening egg white
      antigen as part of the tests for antigens responsible for allergic diseases and
      as a test to ascertain the relevant antigens, and that the conditions that could
      not be diagnosed by RAST can be detected by the AIR test.

PMID- 9761017
TI  - Allergenic and antigenic activity of peptide fragments in a whey hydrolysate
      formula.
AB  - BACKGROUND: Milk hydrolysates, although frequently used as substitutes in cases
      of cow's milk allergy, show a reduced but never a complete abolishment of
      antigenicity and allergenicity. OBJECTIVE: Our purpose was to determine the lower
      molecular weight limit of peptides to elicit skin reactions and to bind IgE
      antibodies in vitro. METHODS: Using FPLC, an ultrafiltrated whey hydrolysate, was
      fractionated in different molecular weight fractions. Skin-prick tests were
      performed with the hydrolysate and its fractions in five cow's milk allergic
      children, and RAST inhibition tests were done using the serum of these children.
      RESULTS: On the basis of the lowest extinction values between two peaks of the
      chromatogram, seven fractions with molecular weights between 15000 and 125 Da
      were obtained. Peptides of > 2600 Da elicited a clearly positive skin reaction
      and inhibited IgE-binding, while peptides of < 1400 Da did not give any positive
      skin reaction but were still able to inhibit to a small extent IgE-binding to the
      hydrolysate. CONCLUSION: Our findings suggest that for skin reactivity peptides
      of > 1400 Da are needed. The minimal molecular mass for IgE binding in vitro
      appears to be situated between 1400 and 970 Da. Such peptides might be used to
      develop a safe formula for patients reacting to milk hydrolysates or even for
      tolerance induction.

PMID- 9761018
TI  - Correlation among urinary eosinophil protein X, leukotriene E4, and 11
      dehydrothromboxane B2 in patients with spontaneous asthmatic attack.
AB  - Various kinds of cells and their mediators are thought to be involved in the
      pathogenesis of bronchial asthma. However, changes in each mediator or
      relationship among mediators during an asthmatic attack have not been well
      documented. In this study, to clarify whether eosinophil protein X (EPX) is a
      marker which is distinct from leukotriene E4 (LTE4), or 11-dehydrothromboxane B2
      (11DTXB2), we measured the urinary excretion of EPX, LTE4, and 11DTXB2 in 14
      asthmatics who were admitted to the hospital with either an acute asthmatic
      attack or status asthmaticus. These patients included eight atopic and six non
      atopic types of bronchial asthma, with a median age of 34.0 years. Urinary
      excretion of EPX was significantly high on admission with the asthmatic attack,
      and returned to control levels 175 [122 -384] microg/day when the patients were
      in the improved state (1036-317 microg/day, P < 0.01). Similar findings were
      observed in LTE4 (155-59 ng/day, P < 0.01) and 11DTXB2 (991-442ng/day, P<0.01).
      No significant differences in values were observed between atopic and non-atopic
      types of asthma in all three substances. When the individual data during the
      attack state were analysed, a significant correlation was observed between
      changes (%) in urinary EPX and those in urinary LTE4, but no such relationship
      was observed between changes (%) in urinary EPX and those in urinary 11DTXB2.
      These results suggest that measuring urinary EPX levels may be a useful marker
      for the understanding and management of the disease.

PMID- 9761019
TI  - GM-CSF, IL-5 and RANTES immunoreactivity and mRNA expression in chronic
      hyperplastic sinusitis with nasal polyposis (NP).
AB  - BACKGROUND: Eosinophils are a prominent feature of chronic hyperplastic sinusitis
      with nasal polyposis (CHS/NP). Our previous studies showed that their presence
      was associated with the expression of GM-CSF and RANTES mRNA. In allergic NP,
      increased expression of IL-5 was also found. OBJECTIVE: We wished to examine
      cytokine immunoreactivity for IL-5, GM-CSF and RANTES mRNA in allergic and non
      allergic NP and compare immunoreactivity with expression of cytokine mRNA by in
      situ hybridization. Methods NP were obtained from five allergic and eight non
      allergic subjects with CHS/ NP. Middle turbinate tissue from eight normal
      subjects were used as controls. Cell-associated cytokine mRNA was detected by in
      situ hybridization (ISH). Cytokine immunoreactive cells were enumerated by
      immunostaining. Colocalization immunostaining was also performed to identify
      specific cell types producing IL-5. RESULTS: Immunostaining for GM-CSF, IL-5 and
      RANTES protein was increased in both allergic and non-allergic NP compared with
      control middle turbinates. Allergic polyps contained greater numbers of IL-5
      immunoreactive cells (P = 0.01), whereas non-allergic polyps contained greater
      numbers of GM-CSF immunoreactive cells (P = 0.04). Immunostaining was primarily
      associated with inflammatory cells, but immunostaining for RANTES and, to a
      lesser extent GM-CSF, was also seen in the epithelium. The density of
      immunoreactive cells was variably correlated with cytokine mRNA+ cells (GM-CSF:
      R=0.56, P=0.05; IL-5: R=0.76, P=0.003; and RANTES: R=0.89, P=0.0005).
      Colocalization immunostaining revealed that the majority of IL-5 immunoreactive
      cells in both allergic and non-allergic NP were T lymphocytes. However, allergic
      NP contained greater numbers of IL-5+/CD3+ T lymphocytes and IL-5+ mast cells,
      whereas non-allergic NP contained greater numbers of IL-5+ eosinophils.
      CONCLUSION: We conclude that GM-CSF, IL-5 and RANTES are produced in increased
      amounts in both allergic and non-allergic NP. Distinguishing features of non
      allergic NP include fewer numbers of CD3 T lymphocytes, fewer IL-5+/CD3+ T
      lymphocytes and greater numbers of IL-5+ eosinophils. These differences may
      suggest different mechanisms of eosinophil accumulation and activation in
      allergic vs non-allergic NP.

PMID- 9761020
TI  - Association of pyrazolone drug hypersensitivity with HLA-DQ and DR antigens.
AB  - BACKGROUND: In sensitive patients pyrazolone drugs can precipitate adverse
      reactions ranging from urticaria and angioedema to anaphylactic shock, presumably
      by immunological, IgE-mediated mechanism. However, up to now no genetic factors
      influencing the development of allergic reaction have been reported in this type
      of hypersensitivity. OBJECTIVE: The aim of our study was the investigation
      whether the susceptibility to development of pyrazolone drugs hypersensitivity
      (PDH) reactions was associated with HLA class II antigens. METHODS: To test this
      hypothesis we studied the distribution of HLA-DR and DQ antigens in 26 pyrazolone
      sensitive patients and control groups including unselected general population and
      clearly defined atopic and non-atopic groups. RESULTS: Significantly higher
      frequencies of DQ 7 and DR11 antigens were found in PDH group as compared with
      control unselected population (RR= 16.48, P < 0.0001; P(cor)< 0.002 and RR =
      4.57, P = 0.0002; Pcor = 0.003 for DQ and DR antigen respectively). Similarly,
      statistically significant increased frequencies of DQ 7 and DR11 in patients with
      PDH were observed compared with atopic control group (RR= 18.43, P < 0.0001; Pcor
      <0.002 and RR= 6.33, P= 0.0007; Pcor =0.01, for DQ and DR antigen respectively).
      However, in comparison to non-atopic control group only the frequency of DQ 7
      antigen was significantly increased (RR = 15.42, P = 0.0001; Pcor = 0.0015). DQ 7
      antigen was present in 46.1% of PDH patients compared with 4.9%, 4.4% and 5.3% in
      the general population, atopic and non-atopic groups respectively, suggesting
      pyrazolone hypersensitivity as a trait positively correlated with this HLA
      antigen. CONCLUSION: Our data suggest a genetic predisposition to pyrazolone
      hypersensitivity reactions, linked to HLA-DQ locus.

PMID- 9761021
TI  - Oilseed rape allergy presented as occupational asthma in the grain industry.
AB  - BACKGROUND: There have been several reports on respiratory allergic symptoms
      induced by pollen of oilseed rape. To the best of our knowledge, this is the
      first report dealing with oilseed rape dust mainly composed of seeds, as an
      occupational allergen in the grain industry. In this paper, we present a case of
      occupational asthma caused by oilseed rape dust from the Animal Feed Industry,
      which proved to be induced by an IgE-mediated reaction. METHODS AND RESULTS: The
      patient displayed positive responses to Dermatophagoides farinae as well as
      oilseed rape dust extract. The bronchoprovocation test showed an early asthmatic
      response to oilseed rape dust extract. Serum specific IgE antibody to oilseed
      rape antigen was detected by enzyme-linked immunosorbent assay (ELISA). ELISA
      inhibition test showed significant inhibitions with addition of oilseed rape
      antigen. In order to further identify the allergenic components of extract,
      sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and
      immunoblot analysis were performed. Fourteen IgE-binding components ranging from
      10 to 160kDa were detected within the oilseed rape extract. CONCLUSION: These
      results suggest that the inhalation of oilseed rape dust, not pollen, can cause
      IgE mediated bronchoconstriction in an exposed worker of the grain industry.

PMID- 9761022
TI  - Participation of T lymphocytes in cutaneous allergic reactions to drugs.
AB  - Immunological mechanisms implicated in drug allergic reactions are not yet well
      understood, but there is 'in vivo' and 'in vitro' evidence that T lymphocytes are
      involved in these hypersensitivity reactions. The cutaneous lymphocyte-associated
      antigen (CLA) is the skin homing receptor and is involved in targeting a skin
      selective memory T lymphocyte to cutaneous sites of chronic inflammation. We have
      seen that CLA expression is increased in circulating T lymphocytes of patients
      who develop a drug allergic cutaneous reaction, these cells are activated and
      their CLA values tend to become normal in parallel with the disappearance of skin
      symptoms, demonstrating that CD3+ CLA+ cells are involved in the immunological
      mechanisms responsible for the pathogenesis of the chronic inflammation process
      in cutaneous drug reactions.

PMID- 9761023
TI  - Presentation of non-peptide antigens, in particular drugs, to specific T cells.
AB  - Drugs are non-peptide antigens that can be recognized by specific T cells. It has
      been thought for many years that small molecular compounds can only be
      stimulating for T cells after covalent binding to MHC-embedded peptides. As most
      drug-specific T cell clones can react to glutaraldehyde fixed antigen presenting
      cells (APC), recognition of drugs by specific T cells does not require prior
      uptake and processing of haptenated proteins by APC. In fact, activated T cell
      clones can recognize drugs associated with the MHC-peptide complex in a non
      covalent way. Such a binding is reminiscent of superantigen stimulations of T
      cells.

PMID- 9761024
TI  - Allergic hepatitis: a drug-mediated organ-specific immune reaction.
AB  - Idiosyncratic toxicity (i.e. adverse reactions to drugs that occur only in
      certain individuals) is a major concern in drug toxicity and drug development.
      This type of adverse reaction may appear during the clinical use of a drug,
      cannot easily be explained in terms of an exaggerated pharmacological side-effect
      of the compound, and is very difficult to anticipate from the preclinical
      studies. Hepatic idiosyncratic reactions fall within two categories: those that
      are the consequence of an unusual metabolism of the drug (metabolic idiosyncrasy)
      and those resulting from an immune-mediated cell injury to hepatocytes which have
      been in contact with the drug previously (allergic hepatitis). In the former
      case, the toxicity is dose-dependent, while in the latter, toxicity may appear
      after several asymptomatic administrations of the compound (sensitization
      period). The mechanisms that trigger the immune response have not yet been
      precisely defined. Current understanding of how drug allergy arises is based
      largely on the hapten hypothesis. Most drugs are not chemically reactive but can
      be activated metabolically to reactive species which, after binding to cellular
      macromolecules, become immunogenic and can elicit an effective immune response.
      Presentation of drug-protein adducts by professional cells to TH lymphocytes,
      and/or a direct association between the drug and MHC proteins of hepatocytes
      could be involved in the activation of the immune system. As a consequence of
      this, drug-directed antibodies and/or T-lymphocytes able to recognize drug
      derived haptens arise which are responsible for the clinical manifestations of
      the hepatitis. Drug-directed antibodies can be detected in sera of allergic
      patients by solid-phase immunoassays. Sensitized T-lymphocytes can be shown by
      hapten-induced cell proliferation experiments and by the early expression of CD69
      antigen.

PMID- 9761025
TI  - Metabolites and allergic drug reactions.

PMID- 9761026
TI  - New aspects in betalactam recognition.
AB  - The data presented in this review confirm that penicillin continues to be the
      most well defined model for studying drug allergy. The identification of new
      specificities has improved the understanding of allergy to penicillins, and
      different well defined subgroups now exist. The capacity of humans to respond to
      unique penicillin determinants has shown that although penicillin is a very small
      molecule it can be recognized in different ways by different IgE antibodies.
      These well defined models have left open the possibility that other betalactams
      can also induce specific reactions which implies that for diagnostic purposes, in
      addition to classical determinants, others are required for in vitro and/or in
      vivo evaluation. When the different subgroups now recognized are compared, not
      only are there differences in the manner of hapten recognition but also in the
      evolution of the natural sensitivity and in the capacity for recognizing other
      structures. The recognition of betalactams by T cells is also important and a
      number of studies have shown that subjects respond specifically to some
      aminopenicillins or cephalosporins with good tolerance to benzylpenicillin. The
      confirmation that these responses can be a T-cell-mediated reaction have been
      reported not only in vitro by the generation of T cell lines and T cell clones
      but also in vivo doing skin biopsies in subjects who have developed different
      types of delayed cutaneous reactions [44]. More studies are needed to determine
      the structure of T cell epitopes and this will help for a better understanding of
      both the IgE and IgG-mediated reactions.

PMID- 9761027
TI  - Delayed hypersensitivity to aminopenicillins.

PMID- 9761028
TI  - T-cell response in penicillin allergy.
AB  - Drugs, such as antibiotics, become immunogenic only upon binding to proteins.
      Among beta-lactams, penicillins constitute a typical example of allergy inducing
      drugs in humans. Previous work on their immunological properties focused mainly
      on the examination of IgE-mediated hypersensitivity reactions. However, drug
      specific T-cell reactions are also involved in causing a serious allergic
      inflammatory response. The experimental data on the reactivity of T cells with
      penicillin G point to penicilloyl-modified, MHC-associated peptides as T-cell
      epitopes. The recognition specificity of the respective T-cell receptors appears
      to be directed at both, the backbone and the specific side-chain of penicillin.
      In contrast, the sequence of the carrier peptides contribute as holder for the
      haptenic determinant.

PMID- 9761029
TI  - Beta-lactam crossreactivity.

PMID- 9761030
TI  - Mechanisms implicated in adverse reactions to non-steroidal anti-inflammatory
      drugs.

PMID- 9761031
TI  - Severe delayed adverse reactions to non-steroidal anti-inflammatory drugs
      (NSAIDs).

PMID- 9761032
TI  - NSAIDS intolerance: clinical and diagnostic aspects.

PMID- 9761033
TI  - New trends in aspirin sensitivity.

PMID- 9761034
TI  - Hypersensitivity reactions to drugs in HIV-infected patients. Allergic evaluation
      and desensitization.

PMID- 9761035
TI  - General and epidemiological aspects of allergic drug reactions.

PMID- 9761036
TI  - Acute drug desensitization.
AB  - Evidence is accumulating that supports a role for acute desensitization for IgE
      mediated drug allergy in those patients for whom no alternative drug exists.
      While most of the studies have been performed in penicillin-allergic patients,
      this procedure has been used safely in patients with IgE sensitivity to other
      agents. In addition, it has been shown that modified desensitization protocols
      may be effective in the prevention of other immune-mediated drug reactions, as
      well. Thus, while much research remains to be done in this area, drug
      desensitization will continue to be a powerful tool in the management of drug
      allergy.

PMID- 9761037
TI  - Diagnosis and pathogenesis of the anaphylactic and anaphylactoid reactions to
      anaesthetics.
AB  - Immediate adverse reactions to anaesthetics have an immune mechanism in more than
      50% of the cases. They are mainly due to muscle relaxant drugs. A prospective
      evaluation of tryptase, histamine and serotonin for diagnosing anaphylaxis to
      anaesthetics was performed over 2 years. The sensitivity of each marker was at 60
      70% and it reached 80% when combining tryptase and histamine. Specific IgE have
      been already observed in serum from patients allergic to muscle relaxant,
      thiopentone, morphine, phenoperidine, propofol and radio-contrast media. However,
      the recent progress in the identification of drug epitopes by Sepharose-solid
      drug phase IgE radioimmunoassay has to be reconsidered as non-specific binding of
      hydrophobic drugs such as propofol to hydrophobic serum IgE has been observed
      recently in patients with drug allergy. In addition, association of drugs such as
      propofol and muscle relaxant may potentiate the mediator release by a non
      elucidated mechanism.

PMID- 9761038
TI  - Immunological investigation in hepatic drug reactions.

PMID- 9761039
TI  - Protein haptenation by drugs.

PMID- 9761040
TI  - 'In vivo' models of hapten generation.

PMID- 9761041
TI  - The connection between basic research and clinical practice.

PMID- 9761042
TI  - Factors affecting excitatory amino acid release following severe human head
      injury.
AB  - OBJECT: Recent animal studies demonstrate that excitatory amino acids (EAAs) play
      a major role in neuronal damage after brain trauma and ischemia. However, the
      role of EAAs in patients who have suffered severe head injury is not understood.
      Excess quantities of glutamate in the extracellular space may lead to
      uncontrolled shifts of sodium, potassium, and calcium, disrupting ionic
      homeostasis, which may lead to severe cell swelling and cell death. The authors
      evaluated the role of EEAs in human traumatic brain injury. METHODS: In 80
      consecutive severely head injured patients, a microdialysis probe was placed into
      the gray matter along with a ventriculostomy catheter or an intracranial pressure
      (ICP) monitor for 4 days. Levels of EAAs and structural amino acids were analyzed
      using high-performance liquid chromatography. Multifactorial analysis of the
      amino acid pattern was performed and its correlations with clinical parameters
      and outcome were tested. The levels of EAAs were increased up to 50 times normal
      in 30% of the patients and were significantly correlated to levels of structural
      amino acids both in each patient and across the whole group (p < 0.01). Secondary
      ischemic brain injury and focal contusions were most strongly associated with
      high EAA levels (27+/-22 micromol/L). Sustained high ICP and poor outcome were
      significantly correlated to high levels of EAAs (glutamate > 20 micromol/L; p <
      0.01). CONCLUSIONS: The release of EAAs is closely linked to the release of
      structural amino acids and may thus reflect nonspecific development of membrane
      micropores, rather than presynaptic neuronal vesicular exocytosis. The magnitude
      of EAA release in patients with focal contusions and ischemic events may be
      sufficient to exacerbate neuronal damage, and these patients may be the best
      candidates for treatment with glutamate antagonists in the future.

PMID- 9761043
TI  - A multicenter trial on the efficacy of using tirilazad mesylate in cases of head
      injury.
AB  - OBJECT: The authors prospectively studied the efficacy of tirilazad mesylate, a
      novel aminosteroid, in humans with head injuries. METHODS: A cohort of 1120 head
      injured patients received at least one dose of study medication (tirilazad or
      placebo). Eighty-five percent (957) of the patients had suffered a severe head
      injury (Glasgow Coma Scale [GCS] score 4-8) and 15% (163) had sustained a
      moderate head injury (GCS score 9-12). Six-month outcomes for the tirilazad- and
      placebo-treated groups for the Glasgow Outcome Scale categories of both good
      recovery and death showed no significant difference (good recovery in the
      tirilazad-treated group was 39% compared with the placebo group in which it was
      42% [p=0.461]; death in the tirilazad-treated group occurred in 26% of patients
      compared with the placebo group, in which it occurred in 25% [p=0.750]). Subgroup
      analysis suggested that tirilazad mesylate may be effective in reducing mortality
      rates in males suffering from severe head injury with accompanying traumatic
      subarachnoid hemorrhage (death in the tirilazad-treated group occurred in 34% of
      patients; in the placebo group it occurred in 43% [p=0.026]). No significant
      differences in frequency or types of serious adverse events were shown between
      the treatment and placebo groups. CONCLUSIONS: Striking problems with imbalance
      concerning basic prognostic variables were observed in spite of the large
      population studied. These imbalances concerned pretreatment hypotension,
      pretreatment hypoxia, and the incidence of epidural hematomas. In future trials
      of pharmacological therapy for severe head injury, serious consideration must be
      given to alternative randomization strategies. Given the heterogeneous nature of
      head injury and the identification of populations that do relatively well with
      standard therapy, target populations with a higher risk for mortality and
      morbidity may be more suitable for clinical trials of such agents.

PMID- 9761044
TI  - Early changes in middle cerebral artery blood flow velocity after head injury.
AB  - OBJECT: This study was designed to investigate the incidence of early
      abnormalities in the cerebral circulation after head injury by relating the
      results of the initial computerized tomography (CT) scan with transcranial
      Doppler (TCD) ultrasound readings to see if the side of injury and the outcome
      can be predicted by using these modalities. METHODS: Transcranial Doppler
      ultrasound measurements were obtained in the emergency room in 22 head-injured
      patients less than 3 hours after injury. The middle cerebral artery (MCA) was
      insonated using a standard technique. The TCD measurements in each MCA were
      examined individually; of 39 measurements, 22 (56%) showed a low mean blood flow
      velocity, 27 (69%) demonstrated a high pulsatility index (PI), and 18 (46%)
      showed both abnormalities. The side of the cerebrovascular abnormality measured
      by TCD ultrasound did not appear to be an accurate predictor of the side of the
      injury as determined on the initial CT scan. Of 13 patients in whom either a
      space-occupying hematoma or signs of swelling were shown on the initial CT scan,
      10 (77%) had an increased PI in one or both MCAs, which is an indication of high
      flow resistance. CONCLUSIONS: Transcranial Doppler ultrasound examinations
      performed while patients are in the emergency room may have a role in determining
      treatment priorities, especially in those with multiple injuries.

PMID- 9761045
TI  - Cerebral monitoring by means of oximetry and somatosensory evoked potentials
      during carotid endarterectomy.
AB  - OBJECT: Cerebral ischemia that occurs during carotid endarterectomy is commonly
      monitored by means of somatosensory evoked potentials (SSEPs) and
      electroencephalography (EEG). The authors conducted this study to determine
      whether cerebral ischemia could also be reliably detected by cerebral oximetry.
      METHODS: Twenty-nine patients who underwent carotid endarterectomy were monitored
      by means of SSEPs, EEG, and cerebral oximetry with a model NIRO500 (20 patients)
      or INVOS3100A (nine patients) oximeter. Changes in amplitude of SSEPs were graded
      as follows: 0, no change; 1, decrease of less than 50%; 2, decrease of greater
      than 50%; and 3, 100% decrease. As measured with the NIRO500 oximeter, closing
      the common caro-tid artery decreased mean oxyhemoglobin levels twice as much (p <
      0.005) in the group with SSEPs of 1 to 3 (-13.11+/-5.59 microM [mean+/-standard
      deviation], 12 patients) as in the group with SSEPs of 0 (-6.22+/-5.59 microM,
      eight patients). The rise in deoxyhemoglobin was also greater (p < 0.05). Two of
      nine patients monitored with the INVOS3100A oximeter had SSEPs of 1 and 3, and
      their regional saturation of oxygen (rSO2) values fell by -11.50 and -11.51,
      respectively. In the remaining seven patients with SSEPs of 0, the rSO2 ranged
      between -2.00 and -6.10 with no overlap with the group with SSEPs of I to 3. The
      increase in oxyhemoglobin monitored using the NIRO500 oximeter and rSO2 monitored
      using the INVOS3100A machine after opening the external carotid artery was less
      than that seen after opening the internal carotid artery. Both types of oximeters
      could detect cerebral ischemia but whereas false negatives occurred with the
      NIRO500, none was observed with the INVOS3100A. Extracranial contamination was
      also four times less frequent with the INVOS3100A than with the NIRO500 monitor.
      CONCLUSIONS: The results indicate that at least as measured with the INVOS3100A
      instrument, a decrease in rSO2 of -10 or more or a decrease below an rSO2 of 50
      is indicative of cerebral ischemia of sufficient severity to decrease the
      amplitude of SSEPs.

PMID- 9761046
TI  - Arterial aneurysms associated with cerebral arteriovenous malformations:
      classification, incidence, and risk of hemorrhage.
AB  - OBJECT: The goal of this study was to develop a classification system for
      aneurysms associated with arteriovenous malformations (AVMs) based on their
      anatomical and pathophysiological relationships and to determine the incidence
      and bleeding rates for these aneurysms as well as the effects of AVM treatment on
      their natural history. METHODS: Of 632 patients with AVMs, intranidal aneurysms
      were found in 35 (5.5%) and flow-related aneurysms in 71 (11.2%). Patients with
      intranidal aneurysms presented more frequently with hemorrhage (72% compared with
      40%, p < 0.001) and had a 9.8% per year risk rate of bleeding during follow-up
      review. Twelve (17%) of the patients with flow-related aneurysms associated with
      an AVM presented with hemorrhage from an aneurysm, whereas 15 (21%) bled from
      their AVM. Seventeen patients underwent angiography after AVM treatment (mean
      2.25 years). Of 23 proximal aneurysms, 18 (78.3%) were unchanged, four (17.4%)
      were smaller, and one (4.3%) had disappeared, whereas four (80%) of five distal
      aneurysms regressed completely and one was unchanged. Sixteen patients underwent
      angiography after partial AVM treatment (mean 3.8 years). In cases with less than
      a 50% reduction in the AVM, no aneurysms regressed, although two enlarged and
      bled. In cases with greater than a 50% reduction in the AVM, two of three distal
      aneurysms disappeared and five proximal aneurysms were unchanged. CONCLUSIONS:
      Arterial aneurysms associated with cerebral AVMs may be classified as intranidal,
      flow-related, or unrelated to the AVM nidus. Intranidal aneurysms have a high
      correlation with hemorrhagic clinical presentation and a risk of bleeding during
      the follow-up period that considerably exceeds that which would be expected in
      their absence. Patients with flow-related aneurysms in association with an AVM
      may present with hemorrhage from either lesion. Aneurysms that arise on distal
      feeding arteries near the nidus have a high probability of regressing with
      substantial or curative AVM therapy.

PMID- 9761047
TI  - The descriptive epidemiology of craniopharyngioma.
AB  - OBJECT: In this report the authors describe the epidemiology of
      craniopharyngioma. METHODS: The incidence of craniopharyngioma in the United
      States was estimated from two population-based cancer registries that include
      brain tumors of benign and borderline malignancy: the Central Brain Tumor
      Registry of the United States (CBTRUS) and the Los Angeles county Cancer
      Surveillance Program. Information on additional pediatric tumors was available
      from the Greater Delaware Valley Pediatric Tumor Registry (GDVPTR). The overall
      incidence of craniopharyngioma was 0.13 per 100,000 person years and did not vary
      by gender or race. A bimodal distribution by age was noted with peak incidence
      rates in children (aged 5-14 years) and among older adults (aged 65-74 years in
      CBTRUS and 50-74 years in Los Angeles county). Survival information was available
      from GDVPTR and the National Cancer Data Base (NCDB), a hospital-based reporting
      system. In the NCDB, the 5-year survival rate was 80% and decreased with older
      age at diagnosis. Survival is higher among children and has improved in recent
      years. CONCLUSIONS: Craniopharyngioma is a rare brain tumor of uncertain behavior
      that occurs at a rate of 1.3 per million person years. Approximately 338 cases of
      this disease are expected to occur annually in the United States, with 96
      occurring in children from 0 to 14 years of age.

PMID- 9761048
TI  - Metastatic brain tumors with dural extension.
AB  - OBJECT: Twenty-two patients who had solitary metastatic brain tumors with dural
      extension were treated surgically over a 3-year period. Their cases were reviewed
      to characterize these lesions and to compare the patients with a similar cohort
      in which there was no dural involvement. METHODS: The median age of the patients
      was 58 years (range 11-68 years) and the male/female ratio was 12:10. The median
      preoperative Karnofsky Performance Scale (KPS) score in the group was 90 (range
      70-100). The most common histological diagnoses seen in these patients included
      breast cancer, adenocarcinoma and squamous cell carcinoma of the lung, and renal
      cell carcinoma. All patients underwent gross-total resection of the tumor and 86%
      received radiation therapy. The median patient survival time was 11 months, with
      a median time to recurrent intracranial disease of 19 months. Survival was
      related to the histological diagnosis. Recurrent disease occurred in 41% of
      cases. Leptomeningeal disease occurred in three patients (14%). The frequency and
      time course of development of recurrent disease was not affected by dural
      resection nor was survival. These results for patients having metastatic brain
      tumors with dural extension were compared with those for a cohort of 26 patients
      in which there were similar histological diagnosis, age, gender, and preoperative
      KPS score were distributed similarly but in which each patient had a single
      subcortical metastatic lesion. Those patients had a median survival of 10 months
      and the median time to recurrence was not reached. Leptomeningeal disease
      occurred in one patient (4%). CONCLUSIONS: To the authors' knowledge, this is the
      first reported series of patients with metastatic brain tumors with dural
      extension. Patients with this disease may be more likely to develop recurrences
      along the dura and leptomeningeal disease, but the overall survival time in these
      patients is not different from those patients with intraparenchymal lesions.

PMID- 9761049
TI  - Detection of soluble E-selectin, ICAM-1, VCAM-1, and L-selectin in the
      cerebrospinal fluid of patients after subarachnoid hemorrhage.
AB  - OBJECT: The goal of this study was to explore whether the levels of soluble
      adhesion molecules were elevated in cerebrospinal fluid (CSF) after subarachnoid
      hemorrhage (SAH). This association was suggested by the known inflammatory
      response in vasospasm and the role of vascular adhesion molecules in regulating
      leukocytic adhesion to, and migration across, vascular endothelium. METHODS: A
      prospective analysis was performed on CSF samples obtained in 17 patients who had
      suffered a recent aneurysmal SAH and in 16 control patients by using quantitative
      enzyme-linked immunosorbent assays for E-selectin, intercellular adhesion
      molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and L-selectin.
      Levels of soluble forms of E-selectin (p=0.0013), ICAM-1 (p=0.0001), and VCAM-1
      (p=0.048) were found to be elevated in the CSF of patients after SAH compared
      with levels in the CSF of norminal controls, patients with unruptured aneurysms,
      and patients tested months after SAH occurred. In addition, individual patients
      tested at the time of their initial ictus demonstrated a fall in adhesion
      molecule levels over time. Levels of E-selectin (p=0.044) were highest in
      patients who later developed moderate or severe vasospasm. CONCLUSIONS: Adhesion
      molecules are known to be involved in white cell adherence to the endothelium and
      subsequent diapedesis and migration in which a role in initiation of tissue
      damage is postulated. The authors have demonstrated the elevation of three
      adhesion molecules, with severely elevated levels of E-selectin seen in patients
      who later develop vasospasm. A correlation with a role of vascular adhesion
      molecules in the pathogenesis of cerebral vasospasm is suggested.

PMID- 9761050
TI  - Changing central nervous system control following intercostal nerve transfer.
AB  - OBJECT: The goal of this study was to find which central nervous system (CNS)
      pathways are involved in volitional control over reinnervated biceps or pectoral
      muscles. METHODS: Intercostal nerves (ICNs) were coapted to the musculocutaneous
      nerve (MCN) or the medial pectoral nerve (MPN) in 23 patients with root avulsions
      of the brachial plexus to restore biceps or pectoral muscle function. The
      facilitatory effects of respiration and voluntary contraction on cortical motor
      evoked potentials of biceps or pectoral muscles were used to study CNS control
      over the reinnervated muscles. The time course of the facilitatory effect of
      respiration and voluntary contraction differed significantly. In the end stage of
      nerve regeneration, the facilitatory effect of voluntary contraction was
      significantly larger than that of respiration, indicating that the CNS control
      network over the muscle comes to resemble that of the recipient nerve (MCN or
      MPN) rather than that of the donor nerve (ICN). CONCLUSIONS: The strengthening of
      previously subthreshold synaptic connections in a CNS network connecting ICN to
      MCN or MPN neurons may underlie changing excitability.

PMID- 9761051
TI  - Occlusion of the sigmoid sinus after surgery via the presigmoidal-transpetrosal
      approach.
AB  - OBJECT: In this paper the authors report on sigmoid sinus occlusion as a surgical
      complication in seven of 143 operations in which a presigmoidal-transpetrosal
      approach was used. METHODS: Five patients (Cases 1-5) developed occlusion within
      40 days after surgery, and in the remaining two (Cases 6 and 7) occlusion was
      detected 5.4 and 6.4 years postsurgery by means of cerebral venography, which was
      performed in 40 of the remaining 138 patients. Of the two patients with occlusion
      of the hypoplastic transverse sinus, one (Case 1) did not develop symptoms and
      the other (Case 2) developed brain edema with transient aphasia. Of the three
      patients suffering from occlusion of the dominant sigmoid sinus, one (Case 3)
      developed severe intracerebral hemorrhages and had a poor prognosis; one (Case 4)
      developed profuse supra- and infratentorial brain edema with consciousness
      disturbance; and the other (Case 5) developed hemorrhagic infarction in the
      temporal lobe accompanied by aphasia. Two patients whose sinus occlusion was
      detected later (Cases 6 and 7) did not develop symptoms and displayed well
      communicated transverse sinuses. In Case 7, a dural arteriovenous malformation
      formed at the site of the sinus occlusion. Laceration of the sigmoid sinus was
      suspected as the cause of occlusion in Cases 2, 3, and 7; compression of the
      sinus in Cases 5 and 6, sinus laceration and postoperative dehydration in Case 4;
      and laceration and compression of the sinus in Case 1. CONCLUSIONS: Differences
      in the clinical course among these patients were attributed to anatomical
      variations in the venous system. Occlusion of the sigmoid sinus should be weighed
      as a potential complication when selecting candidates for the presigmoidal
      transpetrosal approach.

PMID- 9761052
TI  - Poststroke pain control by chronic motor cortex stimulation: neurological
      characteristics predicting a favorable response.
AB  - OBJECT: The goal of this study was to identify the neurological characteristics
      of patients with poststroke pain who show a favorable response to motor cortex
      (MC) stimulation used to control their pain. METHODS: The neurological
      characteristics of 31 patients treated by MC stimulation were analyzed. In 15
      patients (48%), excellent or good pain control (pain reduction > 60%) was
      achieved for follow-up periods of more than 2 years by using MC stimulation at
      intensities below the threshold for muscle contraction. Satisfactory pain control
      was achieved in 13 (73%) of 18 patients in whom motor weakness in the painful
      area was virtually absent or mild, but in only two (15%) of the 13 patients who
      demonstrated moderate or severe weakness in the painful area (p < 0.01). Muscle
      contraction was inducible in the painful area in 20 patients when stimulated at a
      higher intensity. No such muscle response was inducible in the remaining 11
      patients, no matter how extensively the authors attempted to determine
      appropriate stimulation sites. Satisfactory pain control was achieved in 14 (70%)
      of the 20 patients in whom muscle contraction was inducible, but in only one (9%)
      of the 11 patients in whom muscle contraction was not inducible (p < 0.01). No
      significant relationship was observed between pain control and various sensory
      symptoms, including the presence of hypesthesia, spontaneous dysesthesia,
      hyperpathia, and allodynia, or the disappearance of the N20 component of the
      median nerve-evoked somatosensory scalp potential. No significant relationship
      existed between the effect of MC stimulation on the pain and stimulation-induced
      phenomena, including paresthesia, improvement in motor performance, and
      attenuation of involuntary movements. CONCLUSION: These findings suggest that the
      pain control afforded by MC stimulation requires neuronal circuits that are
      maintained by the presence of intact corticospinal tract neurons originating from
      the MC. Preoperative evaluation of motor weakness of the painful area appears to
      be useful for predicting a favorable response to MC stimulation in the control of
      poststroke pain.

PMID- 9761053
TI  - Fatal cyst formation after fetal mesencephalic allograft transplant for
      Parkinson's disease.
AB  - OBJECT: In recent years, fetal mesencephalic tissue transplant for the treatment
      of Parkinson's disease (PD) has been demonstrated to hold promise, but potential
      complications related to growth of allograft tissue have not been well described.
      This report explores the development and possible causation of a fatal cyst
      arising from a fetal transplant in the brain. METHODS: The authors report the
      case of a 52-year-old woman who underwent bilateral putamenal fetal mesencephalic
      allograft transplant for PD at another hospital. Twenty-three months later she
      presented to the authors' institution in a coma. Admission computerized
      tomography and magnetic resonance (MR) studies revealed a contrast-enhancing
      mural nodule and associated large cyst arising from the left putamen and causing
      brainstem compression. Despite surgical decompression of the cyst, the patient
      did not regain consciousness. Biopsy and autopsy specimens were obtained, along
      with an analysis of the cyst fluid. Genotyping of the nodule and the patient's
      peripheral lymphocytes by using polymerase chain reaction-based microsatellite
      analysis was also performed. Biopsy samples and autopsy histopathological studies
      showed inflammatory cells, hemosiderin-laden macrophages, and astrocytosis.
      Scattered neurons and multiple rests of choroid plexus were also noted. The cyst
      had a thin wall and contained liquid that was identical in composition to
      cerebrospinal fluid (CSF). Genotyping demonstrated the presence of alleles in the
      nodule DNA that were not present in lymphocytic DNA, indicating that the nodule
      contained allograft tissue. CONCLUSIONS: The authors hypothesize that the choroid
      plexus tissue contained in the allograft resulted in CSF production and cyst
      formation at the transplant site, ultimately leading to the patient's herniation
      syndrome. The clinical history and large size of the mural nodule indicate slow
      growth of this allograft site and cyst over time. This case demonstrates that
      unusual patterns of tissue growth can occur in the brain after fetal tissue
      transplant and emphasizes the need for long-term monitoring of posttransplant
      patients by means of MR imaging. Cell sorting should be considered to ensure
      transplant of pure neuronal and astroglial populations.

PMID- 9761054
TI  - Transthoracic vertebrectomy for metastatic spinal tumors.
AB  - OBJECT: Anterior approaches to the spine for the treatment of spinal tumors have
      gained acceptance; however, in most published reports, patients with primary,
      metastatic, or chest wall tumors involving cervical, thoracic, or lumbar regions
      of the spine are combined. The purpose of this study was to provide a clear
      perspective of results that can be expected in patients who undergo anterior
      vertebral body resection, reconstruction, and stabilization for spinal metastases
      that are limited to the thoracic region. METHODS: Outcome is presented for 72
      patients with metastatic spinal tumors who were treated by transthoracic
      vertebrectomy at The University of Texas M. D. Anderson Cancer Center. The
      predominant primary tumors included renal cancer in 19 patients, breast cancer in
      10, melanoma or sarcoma in 10, and lung cancer in nine patients. The most common
      presenting symptoms were back pain, which occurred in 90% of patients, and lower
      extremity weakness, which occurred in 64% of patients. All patients underwent
      transthoracic vertebrectomy, decompression, reconstruction with
      methylmethacrylate, and anterior fixation with locking plate and screw
      constructs. Supplemental posterior instrumentation was required in seven patients
      with disease involving the cervicothoracic or thoracolumbar junction, which was
      causing severe kyphosis. After surgery, pain improved in 60 of 65 patients. This
      improvement was found to be statistically significant (p < 0.001) based on visual
      analog scales and narcotic analgesic medication use. Thirty-five of the 46
      patients who presented with neurological dysfunction improved significantly (p <
      0.001) following the procedure. Thirty-three patients had weakness but could
      ambulate preoperatively. Seventeen of these 33 regained normal strength, 15
      patients continued to have weakness, and one patient was neurologically worse
      postoperatively. Of the 13 preoperatively nonambulatory patients, 10 could walk
      after surgery and three were still unable to walk but showed improved motor
      function. Twenty-one patients had complications ranging from minor atelectasis to
      pulmonary embolism. The 30-day mortality rate was 3%. The 1-year survival rate
      for the entire study population was 62%. CONCLUSIONS: These results suggest that
      transthoracic vertebrectomy and spinal stabilization can improve the quality of
      life considerably in cancer patients with spinal metastasis by restoring or
      preserving ambulation and by controlling intractable spinal pain with acceptable
      rates of morbidity and mortality.

PMID- 9761055
TI  - Direct convective delivery of macromolecules to peripheral nerves.
AB  - OBJECT: Although many macromolecules have treatment potential for peripheral
      nerve disease, clinical use of these agents has been restricted because of
      limitations of delivery including systemic toxicity, heterogeneous dispersion,
      and inadequate distribution. In an effort to overcome these obstacles, the
      authors examined the use of convection to deliver and distribute macromolecules
      into peripheral nerves. METHODS: For convective delivery, the authors used a gas
      tight, noncompliant system that provided continuous flow through a small silica
      cannula (inner diameter 100 microm, outer diameter 170 microm) inserted into a
      peripheral nerve. Increases in the volume of infusion (Vi) (10, 20, 30, 40, and
      80 microl) of 14C-labeled (nine nerves) or gadolinium-labeled (two nerves)
      albumin were infused unilaterally or bilaterally into the tibial nerves of six
      primates (Macaca mulatta) at 0.5 microl/minute. The volume of distribution (Vd),
      percentage recovery, and delivery homogeneity were determined using quantitative
      autoradiography, an imaging program developed by the National Institutes of
      Health, magnetic resonance (MR) imaging, scintillation counting, and kurtosis (K)
      analysis. One animal that was infused bilaterally with gadolinium-bound albumin
      (40 microl to each nerve) underwent MR imaging and was observed for 16 weeks
      after infusion. The Vd increased with the Vi in a logarithmic fashion. The mean
      Vd/Vi ratio over all Vi was 3.7+/-0.8 (mean+/-standard deviation). The
      concentration across the perfused region was homogeneous (K=-1.07). The infusate,
      which was limited circumferentially by the epineurium, followed the parallel
      arrangement of axonal fibers and filled long segments of nerve (up to 6.8 cm).
      Recovery of radioactivity was 75.8+/-9%. No neurological deficits arose from
      infusion. CONCLUSIONS: Convective delivery of macromolecules to peripheral nerves
      is safe and reliable. It overcomes obstacles associated with current delivery
      methods and allows selective regional delivery of putative therapeutic agents to
      long sections of nerve. This technique should permit the development of new
      treatments for numerous types of peripheral nerve lesions.

PMID- 9761056
TI  - Direct convective delivery of macromolecules to the spinal cord.
AB  - OBJECT: Because of the limited penetration of macromolecules across the blood
      spinal cord barrier, numerous therapeutic compounds with potential for treating
      spinal cord disorders cannot be used effectively. The authors have developed a
      technique to deliver and distribute macromolecules regionally in the spinal cord
      by using convection in the interstitial space. METHODS: The authors designed a
      delivery system connected to a "floating" silica cannula (inner diameter 100
      microm, outer diameter 170 microm) that provides for constant volumetric inflow
      to the spinal cord. A solution containing albumin that was either unlabeled or
      labeled with carbon-14 or gadolinium was infused at various volumes (3, 6, 10,
      20, 40, or 50 microl) at a rate of 0.1 microl/minute into the spinal cord dorsal
      columns of nine swine and into the lateral columns of three primates (Macaca
      mulatta). Volume of distribution (Vd), concentration homogeneity, and percentage
      of recovery were determined using scintillation analysis, kurtosis calculation
      (K), and quantitative autoradiography (six swine), magnetic resonance imaging
      (one swine and three primates), and histological analysis (all animals).
      Neurological function was observed for up to 3 days in four of the swine and up
      to 16 weeks in the three primates. The Vd of 14C-albumin was linearly
      proportional (R2=0.97) to the volume of infusion (Vi) (Vd/Vi=4.4+/-0.5; [mean+/
      standard deviation). The increases in Vd resulting from increases in Vi were
      primarily in the longitudinal dimension (R2=0.83 in swine; R2=0.98 in primates),
      allowing large segments of spinal cord (up to 4.3 cm; Vi 50 microl) to be
      perfused with the macromolecule. The concentration across the area of
      distribution was homogeneous (K=-1.1). The mean recovery of infused albumin from
      the spinal cord was 85.5+/-5.6%. Magnetic resonance imaging and histological
      analysis combined with quantitative autoradiography revealed the albumin infusate
      to be preferentially distributed along the white matter tracts. No animal
      exhibited a neurological deficit as a result of the infusion. CONCLUSIONS:
      Regional convective delivery provides reproducible, safe, region-specific, and
      homogeneous distribution of macromolecules over large longitudinal segments of
      the spinal cord. This delivery method overcomes many of the obstacles associated
      with current delivery techniques and provides for research into new treatments of
      various conditions of the spinal cord.

PMID- 9761057
TI  - Role of transforming growth factor-beta1 in the pathogenesis of moyamoya disease.
AB  - OBJECT: Prominent features of moyamoya disease are intimal thickening of the
      cerebral arterial trunks and abundant angiogenesis for collateral blood supplies,
      but its pathogenesis is still unknown. The aim of this study was to test the
      possibility that transforming growth factor-beta1 (TGFbeta1) may play a role in
      the pathogenesis of moyamoya disease. METHODS: The authors used reverse
      transcription-polymerase chain reaction to analyze the expression level of
      TGFbeta1 in smooth-muscle cells cultured from the superficial temporal arteries
      (STAs) and measured the serum level of TGFbeta1 by using enzyme-linked
      immunosorbent assay. Although the STA is not predominantly involved with moyamoya
      disease, it has been used in studies of the pathogenesis of this disease. In this
      report, the STAs from six patients with moyamoya disease and four with
      arteriosclerotic cerebrovascular disease, along with sera from 14 patients with
      moyamoya disease and 10 normal healthy volunteers, were studied. The expression
      of TGFbeta1 was significantly higher in cultured smooth-muscle cells derived from
      the STAs of patients with moyamoya disease than in those derived from the STAs of
      patients with arteriosclerotic cerebrovascular disease (p < 0.05). The serum
      level of TGFbeta1 was also significantly higher in patients with moyamoya disease
      than in controls (p < 0.0005). CONCLUSIONS: Taking into account the functional
      roles of TGFbeta1 in the expression of connective tissue genes and angiogenesis,
      these investigators suggest that TGFbeta1 is associated with the pathogenesis of
      moyamoya disease, including abundant neovascularization, although their findings
      do not necessarily mean that TGFbeta1 is a causative factor in this disease.

PMID- 9761058
TI  - The importance of accurate lesion placement in posteroventral pallidotomy. Report
      of two cases.
AB  - Pallidotomy has become a widely used treatment for medically refractory
      Parkinson's disease. However, the optimal lesion size and location within the
      pallidum have not yet been determined, and the role of repeated pallidotomy
      remains undefined. The authors present two patients who had unsatisfactory
      results after their first unilateral pallidotomy but attained dramatic and long
      lasting improvement with repeated surgery. The results obtained in these cases
      indicate that patients who have a good clinical outcome initially but relapse
      rapidly after surgery should be considered for repeated pallidotomy if the
      initial lesion was not placed in the optimal location.

PMID- 9761059
TI  - Neuroradiological findings in adult cranially conjoined twins. Case report.
AB  - The authors demonstrate the radiological anatomy and review the accepted
      embryological theories in a case of total craniopagus. These 24-year-old female
      cranially conjoined twins were studied with computerized tomography (CT) and CT
      angiography, magnetic resonance (MR) imaging and MR angiography as well as
      selective arterial digital subtraction (DS) angiography to clarify whether
      surgical separation was possible. The neuroradiological findings are discussed,
      taking into consideration both the embryological and surgical literature. The
      malformation was classified as a total parietooccipitotemporal craniopagus.
      Whereas CT angiography and MR imaging including MR angiography demonstrated a
      common superior sagittal sinus, only selective arterial DS angiography revealed a
      significant arterial and venous cross-flow between the two adjacent temporal
      lobes. Selective intraarterial DS angiography is required in the
      neuroradiological evaluation of complex malformations, even when the anatomy of
      brain and skull can be well demonstrated with high-quality MR and CT studies.

PMID- 9761060
TI  - Detection of Bartonella henselae by polymerase chain reaction in brain tissue of
      an immunocompromised patient with multiple enhancing lesions. Case report and
      review of the literature.
AB  - The authors report the first DNA-based diagnosis of Bartonella henselae cultured
      from a brain lesion in a patient with acquired immune deficiency syndrome. This
      human immunodeficiency virus-infected patient presented with altered mental
      status, fever, and diabetes insipidus. Magnetic resonance imaging revealed
      multifocal parenchymal and leptomeningeal involvement, which was confirmed on
      studies of tissue biopsy samples. Using the polymerase chain reaction and gene
      sequencing techniques, the authors definitively demonstrated the presence of B.
      henselae in the brain tissue biopsy specimen.

PMID- 9761061
TI  - Subsidence of seizure induced by stereotactic radiation in a patient with
      hypothalamic hamartoma. Case report.
AB  - The authors report on a patient who exhibited intractable epilepsy due to an
      inaccessible hypothalamic hamartoma and subsequently underwent stereotactic
      radiosurgery. This 25-year-old man had a 24-year history of intractable gelastic
      and tonic-clonic seizures. Magnetic resonance (MR) imaging performed at
      examination as well as that performed 30 months earlier demonstrated a
      nonenhancing and nonprogressive spherical mass, approximately 10 mm in diameter,
      located on the patient's right side at the floor of the third ventricle. Focal
      radiation treatment performed with a gamma knife unit administered 36 Gy to the
      center and 18 Gy to the periphery of the lesion. This treatment resulted in an
      improvement in seizure control. Before the patient underwent radiosurgery, he
      suffered from three to six generalized seizures per month in spite of attentive
      compliance with an anticonvulsant medication regimen. After irradiation of the
      harmatoma, the frequency of the seizures transiently increased and then subsided
      3 months posttreatment. The patient has been free of seizures for the last 21
      months, with no neurological or endocrinological complications. Magnetic
      resonance imaging performed 12 months posttreatment demonstrated complete
      disappearance of the lesion.

PMID- 9761062
TI  - Continuous hemodialysis for the management of acute renal failure in the presence
      of cerebellar hemorrhage. Case report.
AB  - In this report the authors describe the use of continuous venovenous hemodialysis
      (CVVHD) in a medically unstable patient who suffered from a spontaneous
      cerebellar hemorrhage. Conventional dialysis techniques carry the risk of
      developing the dialysis disequilibrium syndrome (DDS) when performed in the
      presence of a variety of intracranial diseases. The CVVHD technique was used
      successfully in a morbidly obese, short-statured woman with a spontaneous
      hypertensive intraparenchymal cerebellar hemorrhage. The woman experienced acute
      renal failure several days after her hemorrhage and her general medical condition
      prevented her from undergoing surgical evacuation. The CVVHD did not result in
      elevations in intracranial pressure (ICP) and the patient made a full recovery
      from both acute renal failure and life-threatening posterior fossa hemorrhage.
      This case is noteworthy because of the absence of abnormally high ICP elevations
      or development of DDS in a patient with a large acute posterior fossa
      intraparenchymal brain hemorrhage and acute renal failure whose case was managed
      with CVVHD in the acute period.

PMID- 9761063
TI  - Death from a malignant cerebellopontine angle triton tumor despite stereotactic
      radiosurgery. Case report.
AB  - Malignant vestibular nerve tumors are rare: to date, only three cases have been
      reported in the literature. The authors report a case of an eighth cranial nerve
      tumor that progressed 5 years after stereotactic radiosurgery. The patient was a
      44-year-old man who underwent stereotactic radiosurgery for a 27-mm
      cerebellopontine angle tumor that was discovered on investigation of tinnitus and
      hearing loss. He developed facial weakness after 5 years, and repeated imaging
      revealed tumor enlargement. Despite complete microsurgical excision, the tumor
      rapidly recurred locally and subsequently disseminated within the neuraxis. The
      patient died 1 year after tumor progression was detected. Histopathological
      analysis revealed a malignant spindle cell neoplasm with frequent mitotic
      figures. The presence of positive rhabdoid elements on immunohistochemical
      studies confirmed that it was a triton tumor. The authors review the relevant
      literature concerning the classification and management of malignant vestibular
      nerve tumors and discuss the implications of tumor progression after stereotactic
      radiosurgery.

PMID- 9761064
TI  - Primary cervical melanoma with brain metastases. Case report and review of the
      literature.
AB  - Primary intramedullary melanoma is a very rare tumor that occurs most frequently
      in the middle or lower thoracic spinal cord. The authors present a case of
      primary cervical cord melanoma that developed in a 62-year-old man who was
      surgically treated and subsequently underwent radiation therapy. Clinical and
      histogenetic features of this neoplasm and results of chemo-. radio-, and
      immunotherapy are reported. Both "dysembryogenetic" and "mesodermal" hypotheses
      on the origin of primary spinal melanoma are discussed.

PMID- 9761065
TI  - Cavernous sinus syndrome during balloon test occlusion of the cervical internal
      carotid artery. Report of two cases.
AB  - The authors report the occurrence of ipsilateral transient cavernous sinus
      syndrome during balloon test occlusion (BTO) of the cervical internal carotid
      artery (ICA) and discuss the involved pathomechanisms. The authors reviewed their
      series of 129 BTOs of the ICA performed between 1989 and 1996. Two patients
      developed facial paresthesias and transient palsies of the third through sixth
      cranial nerves during test occlusion of the cervical ICA. The tests were
      performed prior to planned permanent carotid artery occlusion for the treatment
      of a neck sarcoma in one patient and a giant cavernous carotid artery aneurysm in
      the other. The patients' symptoms resolved with deflation of the balloon. When
      the balloon was subsequently inflated above the inferior cavernous sinus artery
      (ICSA), one of the patients complained of mild facial discomfort. There was no
      contralateral weakness or mental status change during test occlusion in either
      patient. Angiography demonstrated good filling of the ipsilateral intracranial
      circulation via collateral vessels of the circle of Willis. In these two cases,
      the cranial nerves in the cavernous sinus were likely supplied by the ICA via the
      meningohypophyseal trunk and the ICSA. In each case, there was excellent blood
      supply to the ipsilateral cerebral hemisphere; however, there was probably
      inadequate retrograde filling of the cranial nerve collateral vessels located
      where the meningohypophyseal trunk and ICSA originated. These cases emphasize the
      importance of a patent external carotid artery-ICA connection for successful
      cervical carotid artery occlusion. Neurological examination during BTO was
      critical to interpret the clinical manifestations caused by the hemodynamic
      changes.

PMID- 9761066
TI  - Reconstruction of the vein of Labbe by using a short saphenous vein bypass graft.
      Technical note.
AB  - Protection of the vein of Labbe is a significant concern during surgery that
      involves retraction of the temporal lobe. A cranial base surgical approach,
      especially one via the presigmoid-petrosal route, carries considerable risk to
      this venous complex. A case is presented in which a large dominant vein of Labbe
      was injured during resection of a petroclival meningioma. This vein drained all
      the sylvian venous circulation as well as the lateral temporal surface; no
      connection to another venous system was noted. The vein was successfully
      reconstructed using a short saphenous vein bypass graft. Significant
      complications could have occurred without this reconstruction. The technique and
      benefits of this type of reconstruction are discussed.

PMID- 9761067
TI  - Intracranial vascular anastomosis using the microanastomotic system. Technical
      note.
AB  - The authors describe the use of a microanastomotic device to perform intracranial
      end-to-end vascular anastomoses. Direct end-to-end anastomosis was performed
      between the superficial temporal artery and branches of the middle cerebral
      artery (MCA) in three patients. Two patients had moyamoya disease, with severe
      proximal MCA disease, and one suffered an internal carotid artery occlusion with
      poor collateral flow. All patients reported a history of recent ischemic
      symptoms. Each anastomosis was accomplished in less than 15 minutes with
      technically satisfactory results. Postoperative angiographic studies demonstrated
      patency of the bypasses in all patients.

PMID- 9761068
TI  - Infection of a Rathke's cleft cyst: a rare cause of pituitary abscess. Case
      illustration.

PMID- 9761069
TI  - Fibrolipomatous hamartoma of the median nerve. Case illustration.

PMID- 9761070
TI  - Omental transplantation.

PMID- 9761071
TI  - Chordoid meningioma.

PMID- 9761072
TI  - Guidelines or potentially dangerous recommendations? The AANS/CNS Committee on
      Assessment of Quality. American Association of Neurological Surgeons. Congress of
      Neurological Surgeons.

PMID- 9761073
TI  - Radiosurgery and microsurgery for AVMs.

PMID- 9761074
TI  - Radiosurgery and microsurgery for AVMs.

PMID- 9761075
TI  - Doppler ultrasound in subarachnoid hemorrhage.

PMID- 9761076
TI  - Doppler ultrasound in subarachnoid hemorrhage.

PMID- 9761077
TI  - Abciximab administration and outcome after intracoronary stent implantation.
AB  - Although adjunctive abciximab therapy improves outcome after angioplasty or
      atherectomy, there are few data demonstrating its benefit for intracoronary stent
      implantation. We characterized patients receiving abciximab for stent placement
      in our practice and determined the impact of abciximab on outcome. Abciximab was
      introduced to our practice in April 1995 for percutaneous revascularization.
      Demographic, clinical, and angiographic variables that were independently
      associated with the use of abciximab for stent placement through 1996 (abciximab
      era) were examined. We then examined among all patients receiving stents from
      1992 through 1996 (preabciximab and abciximab eras) whether the use of abciximab
      was independently associated with improved outcome (death, nonfatal Q-wave
      myocardial infarction, coronary bypass surgery, or target vessel percutaneous
      revascularization) in the hospital and at 30 days. The 30-day event rate was 7%
      for those who did or did not receive abciximab. The following characteristics
      were independently associated with the use of abciximab for stent placement in
      the abciximab era: thrombus before stent placement (chi-square 50.5), > or =2
      stents implanted (chi-square 10.8), stent in venous graft (chi-square 7.4),
      calcific lesion (chi-square 5.8), and hypertension (chi-square 5.5). Among all
      patients receiving stents in the preabciximab and abciximab eras (n=1,859), the
      presence of these characteristics was independently associated with worse
      outcome. Abciximab, however, did not improve outcome in the hospital (odds ratio
      [95% confidence interval]=0.96 [0.58 to 1.58]) or at 30 days (0.87 [0.53 to
      1.41]), even after adjusting for these characteristics. Abciximab for stent
      placement was used in high-risk patients in our practice but was not associated
      with improved outcome.

PMID- 9761078
TI  - Comparison of coronary endothelial dynamics with electrocardiographic and left
      ventricular contractile responses to stress in the absence of coronary artery
      disease.
AB  - Coronary artery endothelial dysfunction has been proposed as a cause of
      myocardial ischemia and symptoms in patients with angina-like chest pain despite
      normal coronary angiograms, especially those with ischemic-appearing ST-segment
      depression during exercise (syndrome X). We measured coronary vasomotor responses
      to acetylcholine (3 to 300 microg/min) in 42 patients (27 women and 15 men) with
      effort chest pain and normal coronary angiograms who also had normal
      electrocardiograms and echocardiograms at rest. All patients underwent treadmill
      exercise testing and measurement of systolic wall thickening responses to
      dobutamine (40 microg/kg/min) during transesophageal echocardiography. There were
      no differences in the acetylcholine-stimulated epicardial coronary diameter (+5+/
      13% vs +1+/-13%, p=0.386) and flow (+179+/-90% vs +169+/-96%, p=0.756), or in the
      systolic wall thickening responses (+134+/-65% vs +118+/-57%, p=0.445) from
      baseline values in the 12 syndrome X patients compared with the 30 patients with
      negative exercise test results. In patients in the lowest quartile of coronary
      flow responses to acetylcholine, dobutamine increased systolic wall thickening by
      121+/-73%; 3 had ischemic-appearing ST-segment depression during this stress.
      This contractile response to dobutamine was no different than the increase in
      systolic wall thickening (129+/-48%, p=0.777) in patients in the highest quartile
      of coronary flow responses, 3 of whom also had ischemic-appearing ST-segment
      depression during this stress. Thus, coronary endothelial dysfunction in the
      absence of coronary artery disease does not account for ischemic-appearing ST
      segment depression in patients with chest pain despite normal coronary
      angiograms. Further, coronary endothelial dysfunction is not associated with
      myocardial contractile responses to stress consistent with myocardial ischemia.

PMID- 9761079
TI  - Incremental prognostic value of serum levels of troponin T and C-reactive protein
      on admission in patients with unstable angina pectoris.
AB  - Management of unstable angina is largely determined by symptoms, yet some
      symptomatic patients stabilize, whereas others develop myocardial infarction
      after waning of symptoms. Therefore, markers of short-term risk, available on
      admission, are needed. The value of 4 prognostic indicators available on
      admission (pain in the last 24 hours, electrocardiogram [ECG], troponin T, and C
      reactive protein [CRP]), and of Holter monitoring available during the subsequent
      24 hours was analyzed in 102 patients with Braunwald class IIIB unstable angina
      hospitalized in 4 centers. The patients were divided into 3 groups: group 1, 27
      with pain during the last 24 hours and ischemic electrocardiographic changes;
      group 2, 45 with pain or electrocardiographic changes; group 3, 30 with neither
      pain nor electrocardiographic changes. Troponin T, CRP, ECG on admission, and
      Holter monitoring were analyzed blindly in the core laboratory. Fifteen patients
      developed myocardial infarction: 22% in group 1, 13% in group 2, and 10% in group
      3. Twenty-eight patients underwent revascularization: 37% in group 1, 35% in
      group 2, and 7% in group 2 (p <0.01 between groups 1 or 2 vs group 3). Myocardial
      infarction was more frequent in patients with elevated troponin T (50% vs 9%,
      p=0.001) and elevated CRP (24% vs 4%, p= 0.01). Positive troponin T or CRP
      identified all myocardial infarctions in group 3. Only 1 of 46 patients with
      negative troponin T and CRP developed myocardial infarction. Among the indicators
      available on admission, multivariate analysis showed that troponin T (p=0.02) and
      CRP (p=0.04) were independently associated with myocardial infarction. Troponin T
      had the highest specificity (92%), and CRP the highest sensitivity (87%).
      Positive results on Holter monitoring were also associated with myocardial
      infarction (p=0.003), but when added to troponin T and CRP, increased specificity
      and positive predictive value by only 3%. Thus, in patients with class IIIB
      unstable angina, among data potentially available on admission, serum levels of
      troponin T and CRP have a significantly greater prognostic accuracy than symptoms
      and ECGs. Holter monitoring, available 24 hours later, adds no significant
      information.

PMID- 9761080
TI  - Risk stratification of patients with medically treated unstable angina using
      exercise echocardiography.
AB  - Functional testing is recommended for risk stratification of medically treated
      patients with unstable angina. Exercise echocardiography is used in this
      situation, but its safety and prognostic value are not well defined. The
      objective of this study was to assess the incremental prognostic value of
      exercise echocardiography in 226 consecutive patients (128 men, age 59+/-13
      years) with medically treated unstable angina, who underwent exercise
      echocardiography from 1991 to 1996. Clinical risk was designated as low in 108
      patients, intermediate in 116, and high in 2 patients according to the unstable
      angina practice guidelines. There were no major complications from the stress
      tests. The exercise electrocardiogram was nondiagnostic in 57 patients (25%).
      Ischemia was identified by exercise electrocardiography in 33 patients and
      exercise echocardiography in 55 patients. Patients were followed for 29+/-18
      months. After exclusion of 38 patients who underwent early revascularization, 28
      patients had cardiac death, nonfatal infarction, and late (>3 months)
      revascularization. Ischemia at exercise echocardiography was associated with a 24
      month event-free survival of 81%, compared to 95% with negative exercise
      echocardiography (p=0.02). A positive exercise electrocardiogram was associated
      with a 24-month event-free survival of 84%, compared to 93% with negative
      exercise electrocardiograms (p=0.08). In a Cox regression model, event-free
      survival was predicted by ischemia at exercise echocardiography (relative risk
      2.8, confidence interval: 1.3 to 6.3, p=0.05), but not at exercise
      electrocardiography (relative risk 2.1, confidence interval 0.7 to 5.8, p=0.16).

PMID- 9761081
TI  - Incremental prognostic value of adenosine myocardial perfusion single-photon
      emission computed tomography in women with suspected coronary artery disease.
AB  - Adenosine myocardial perfusion single-photon emission computed tomography (SPECT)
      is now increasingly used for risk stratification of patients with known or
      suspected coronary artery disease. However, the incremental prognostic value of
      this test over clinical and historical information in a large series of women has
      not been examined. Thus, we studied 923 consecutive women who underwent adenosine
      technetium (Tc)-99m sestamibi myocardial perfusion SPECT and were followed-up for
      a mean period of 26+/-8 months. During the follow-up period, 77 hard events (46
      cardiac deaths and 31 nonfatal myocardial infarctions) occurred. The results of
      the perfusion scan significantly risk stratified the population; patients with
      normal scans had a low rate of nonfatal myocardial infarction and cardiac death
      (< 1%/year of follow up). Patients with mildly abnormal scans had low cardiac
      death rates (0.9%/year of follow up); these rates increased as a function of scan
      abnormality (4.1% and 7.5% mortality per year of follow up in moderate and
      severely abnormal scans). Cox proportional hazards analysis demonstrated that
      after adjusting for prior myocardial infarction and diabetes mellitus (the most
      predictive individual clinical variables [global chi-square=22.5, p <0.001]), as
      well as heart rate at rest (the most predictive physiologic variable [chi
      square=3.8; p=0.05]), the most predictive nuclear variable (summed stress score
      [chi-square=48.5; p <0.0001]) added significant incremental prognostic
      information (global chi-square increased from 22.5 to 56.2 [p <0.0001]). In
      conclusion, adenosine myocardial perfusion SPECT added significant incremental
      prognostic information to clinical and physiologic variables in women. Normal
      scans were associated with an excellent prognosis. In contrast, patients with
      moderately to severely abnormal scans were at a higher risk for future cardiac
      events.

PMID- 9761082
TI  - Invasive versus conservative strategies in unstable angina and non-Q-wave
      myocardial infarction following treatment with tirofiban: rationale and study
      design of the international TACTICS-TIMI 18 Trial. Treat Angina with Aggrastat
      and determine Cost of Therapy with an Invasive or Conservative Strategy.
      Thrombolysis In Myocardial Infarction.
AB  - In the management of unstable angina and non-Q-wave acute myocardial infarction
      (AMI), there is considerable debate regarding the use of invasive strategy versus
      conservative strategy. The Thrombolysis In Myocardial Infarction (TIMI) III B
      trial found similar clinical outcomes for the 2 strategies, but the Veterans
      Administration Non-Q-Wave Infarction Strategies in-Hospital trial found a higher
      mortality with the invasive strategy. Both these trials were conducted before
      platelet glycoprotein IIb/IIIa inhibition and coronary stenting, both of which
      improve clinical outcome. Thus, there is a need to reexamine the question of
      which management strategy is optimal in the current era of platelet glycoprotein
      IIb/IIIa inhibition and new coronary interventions. The Treat Angina with
      Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy
      (TACTICS-TIMI 18) trial is an international, multicenter, randomized trial that
      is evaluating the clinical efficacy of early invasive and early conservative
      treatment strategies in patients with unstable angina or non-Q-wave AMI treated
      with tirofiban, heparin, and aspirin. Patients are randomized to an invasive
      strategy, involving cardiac catheterization within 4 to 48 hours and
      revascularization with angioplasty or bypass surgery if feasible, versus a
      conservative strategy, where patients are referred for catheterization only for
      recurrent pain at rest or provokable ischemia. The primary end point is death,
      MI, or rehospitalization for acute coronary syndromes through a 6-month follow
      up. The trial is also testing the "troponin hypothesis," that baseline troponins
      T and I will be useful in selecting an optimal management strategy.

PMID- 9761083
TI  - Effectiveness of once-nightly dosing of extended-release niacin alone and in
      combination for hypercholesterolemia.
AB  - We performed a multicenter, open-label study to determine the long-term safety
      and efficacy of a new extended-release once-a-night niacin preparation, Niaspan,
      in the treatment of hypercholesterolemia. Niaspan, 0.5 to 3.0 g once a night at
      bedtime, was used alone or in combination with a statin (inhibitor of
      hydroxymethylglutaryl coenzyme A reductase), a bile acid sequestrant, or both.
      Patients included 269 hypercholesterolemic male and female adults enrolled in a
      96-week study, and 230 additional adults for whom short-term safety data were
      available. The dosages of Niaspan attained by 269 patients were 1,000 mg (95% of
      patients), 1,500 mg (86%), and 2,000 mg (65%). After 48 weeks of treatment,
      Niaspan alone (median dose 2,000 mg) reduced low-density lipaprotein (LDL)
      cholesterol (18%), apolipoprotein B (15%), total cholesterol (11%), triglycerides
      (24%), and lipoprotein(a) (36%), and increased high-density lipoprotein (HDL)
      cholesterol (29%). Niaspan plus a statin lowered LDL cholesterol (32%),
      apolipoprotein B (26%), total cholesterol (23%), triglycerides (30%), and
      lipoprotein(a) (19%), and increased HDL cholesterol (26%). Reversible elevations
      of aspartate aminotransferase or alanine aminotransferase more than twice the
      normal range occurred in 2.6% of patients. One patient discontinued Niaspan
      because of transaminase elevations. Intolerance to flushing, leading to
      discontinuation of Niaspan, occurred in 4.8% of patients. The overall rate of
      discontinuance due to flushing in this study combined with 2 previous randomized
      trials was 7.3%. In the long-term treatment of hypercholesterolemia, Niaspan
      produced favorable changes in LDL and HDL cholesterol, triglycerides, and
      lipoprotein(a). Adverse hepatic effects were minor and occurred at rates similar
      to those reported for statin therapy.

PMID- 9761084
TI  - Comparison of metoprolol and sotalol in preventing ventricular tachyarrhythmias
      after the implantation of a cardioverter/defibrillator.
AB  - The purpose of this prospective study was to evaluate, on an intention-to-treat
      basis, the efficacy of d,l-sotalol and metoprolol with regards to the recurrence
      of arrhythmic events after implantable cardioverter defibrillator (ICD)
      implantation. After ICD implantation, 70 patients were randomly assigned to
      treatment with either metoprolol (mean dosage 104+/-37 mg/day in 35 patients) or
      d,l-sotalol (mean dosage 242+/-109 mg/day in 35 patients). During follow up
      ventricular tachycardia (VT), fast VT, and ventricular fibrillation (VF) episodes
      were calculated. Metoprolol treatment led to a marked reduction in the recurrence
      of arrhythmic events. Actuarial rates for absence of VT recurrence at 1 and 2
      years were significantly higher in the metoprolol group compared with the d,l
      sotalol group (83% and 80% vs 57% and 51%, respectively, p=0.016). The actuarial
      rates for absence of fast VT or VF were 80% in the metoprolol group compared with
      46% in the d,l-sotalol group (p=0.002). During a follow up of 26+/-16 months,
      there were 3 deaths in the metoprolol group compared with 6 deaths in the d,l
      sotalol group. Actuarial rates of overall survival were not significantly
      different in the 2 groups (91% vs 83%, p=0.287). In this prospective, randomized,
      controlled study the recurrence rate of ventricular tachyarrhythmias in patients
      treated with metoprolol was lower than in patients treated by d,l-sotolol.

PMID- 9761085
TI  - Effects of prostacyclin on the pulmonary vascular tone and cardiac contractility
      of patients with pulmonary hypertension secondary to end-stage heart failure.
AB  - Long-term administration of prostacyclin (PGI2) improves the hemodynamic state,
      symptoms, and survival in patients with primary pulmonary hypertension, but it
      increases mortality in patients with heart failure despite obvious hemodynamic
      benefits when it is given acutely. We evaluated the mechanisms of action of PGI2
      in patients with heart failure and secondary pulmonary hypertension. Nineteen
      patients with end-stage heart failure and pulmonary hypertension, all candidates
      for heart transplantation, underwent right- and left sided cardiac
      catheterization with micromanometer-tipped catheters and were tested for PGI2 at
      incremental doses. PGI2 infusion significantly improved pulmonary hemodynamics
      with a 47% reduction in pulmonary vascular resistance (p=0.0003) and a doubling
      of pulmonary artery compliance (p <0.0001), reflecting improvement in pulmonary
      vascular tone. The dose of PGI2 necessary to reach this hemodynamic effect
      correlated significantly to the baseline severity of pulmonary artery compliance
      (r=0.54, p=0.01). Furthermore, PGI2 produced a significant positive inotropic
      effect (contractile element maximum velocity increased from 1.10+/-0.09 to 1.33+/
      0.13 circ/s, p <0.009). The hemodynamic effects of PGI2 infusion were independent
      of the plasma and urinary levels of endogen prostaglandins. Thus, PGI2 at
      therapeutic doses exerts a positive inotropic effect in patients with heart
      failure, which may explain the increased mortality rate observed with the long
      term use of PGI2 in this type of patient. The spectacular acute benefits on right
      ventricular afterload, however, may be useful in unstable patients with heart
      failure and secondary pulmonary hypertension or in transplanted patients with
      acute right ventricular failure of the donor heart.

PMID- 9761086
TI  - Increasing degrees of left ventricular filling impairment modulate left atrial
      function in humans.
AB  - We sought to investigate the changes in atrial reservoir, pump, and conduit
      functions that are associated with increasing degrees of left ventricular filling
      impairment. In 13 patients with an impaired relaxation type of filling and in 15
      with restrictive patterns, the left atrial volume curve was constructed combining
      Doppler and 2-dimensional echocardiography. Nine normal subjects served as
      controls. Left atrial reservoir (defined as [maximum - minimum atrial volume]
      minus the amount of blood flow reversal in the pulmonary veins with atrial
      contraction), pump (defined by the volume of blood that enters the ventricle with
      atrial contraction), and conduit functions (defined as left ventricular filling
      volume - [left atrial reservoir plus pump volume]) were computed and each
      expressed as a percentage of ventricular filling volume. The atrial reservoir
      function was higher in the impaired relaxation group than in normal subjects
      (49+/-8% vs 38+/-8%, p <0.01) but markedly lower in the restrictive group (27+/
      8%, p <0.05). The reverse was true for conduit function, exaggerated in
      restrictive group (54+/-12% vs 36+/-11% in normal subjects, p <0.01) but
      minimized in patients with an impaired relaxation type of filling (14+/-9%, p
      <0.001). The atrial pump contributed 19+/-6% of ventricular filling volume in
      restrictives, 26+/-3% in normals (p <0.01), and 38+/-4% (p <0.001) in the
      impaired relaxation group. We conclude that increased atrial response to early
      stage left ventricular filling impairment is characterized by augmented reservoir
      and pump functions, according to a Starling mechanism, which becomes hardly
      effective at end-stage ventricular dysfunction when the limits of the atrial
      preload reserve are reached. At this stage, conduit in the atrium takes
      precedence.

PMID- 9761087
TI  - Comparison of effects of ascorbic acid on endothelium-dependent vasodilation in
      patients with chronic congestive heart failure secondary to idiopathic dilated
      cardiomyopathy versus patients with effort angina pectoris secondary to coronary
      artery disease.
AB  - Impaired endothelium-dependent vasodilation has been reported to play an
      important role in the pathogenesis of cardiovascular diseases such as coronary
      artery disease (CAD) and congestive heart failure (CHF). However, the precise
      mechanism of endothelial dysfunction has not been elucidated in these conditions.
      To evaluate the role of oxidative stress in endothelial dysfunction, the effect
      of antioxidant ascorbic acid on brachial flow-mediated, endothelium-dependent
      vasodilation during reactive hyperemia and nitroglycerin-induced endothelium
      independent vasodilation was examined with high resolution ultrasound in 12
      patients with CHF caused by idiopathic dilated cardiomyopathy without established
      coronary atherosclerosis and in 10 patients with CAD. Flow-mediated vasodilation
      in CHF (4.4+/-0.5%) and CAD (4.0 - 0.8%) was significantly (p <0.05) attenuated
      compared with that in 10 control subjects (9.6+/-0.9%). However, nitroglycerin
      induced vasodilation was similar in 3 groups (13.7+/-1.3% in control, 13.9+/-1.1%
      in CHF, 12.7+/-1.4% in CAD). Ascorbic acid could significantly improve flow
      mediated vasodilation only in patients with CAD (9.1+/-0.9%) but not with CHF
      (5.6+/-0.6%), and had no influence on nitroglycerin-induced vasodilation (13.6+/
      1.1% in CHF, 14.0+/-1.3% in CAD). These results suggest that, in brachial
      circulation, augmented oxidative stress mainly leads to endothelial dysfunction
      in CAD but not in CHF caused by idiopathic dilated cardiomyopathy.

PMID- 9761088
TI  - Likelihood of underreporting of outlet strut fracture from examination of the
      Dutch Bjork-Shiley CC cohort.
AB  - The Dutch Bjork-Shiley convexo-concave (BScc) cohort serves as a reference
      population on the risk of outlet strut fracture and is being used to formulate
      guidelines for prophylactic replacement. Fractures, however, may be undetected at
      death. The aim of this study was to quantify the degree of underestimation of
      strut fracture in the Dutch BScc cohort. Multivariate Cox regression analysis was
      used to assess the relative and absolute risk of death from different causes
      within 14 years. The unexplained "excess" mortality among 70 degrees BScc valve
      recipients was attributed to unreported fatal strut fractures and used to
      estimate its extent in this group, which then was extrapolated to the 60 degrees
      BScc valve recipients. For 70 degrees BScc valve recipients, the adjusted hazard
      ratio for death from all causes except strut fracture was 1.2 (95% confidence
      interval [CI] 1.0 to 1.5). The 14-year absolute risks for 70 degrees and 60
      degrees BScc valve recipients were 44% and 37%, respectively. Among 70 degrees
      and 60 degrees BScc valve recipients, underreporting of fracture was estimated to
      be 25% (95% CI 0 to 49) and 26% (95% CI 0 to 52), respectively. Estimates based
      on sudden death and fatal congestive heart failure yielded essentially the same
      results. Thus, underreporting of fatal strut fracture in the Dutch BScc cohort is
      estimated to be approximately 25%. Hence, the risk and lethality of fracture of
      BScc valves are underestimated and indications for prophylactic replacement
      should be adjusted accordingly. For example, the advantage of valve replacement
      in a 40-year-old patient with a 29-mm 60 micro BScc mitral valve would almost
      double to 0.82 years.

PMID- 9761089
TI  - Predictors of sudden cardiac death in hypertrophic cardiomyopathy.
AB  - Patients with hypertrophic cardiomyopathy (HC) die suddenly. Proposed risk
      factors for sudden cardiac death (SCD) in HC are youth, a family history of SCD,
      syncope, and ventricular tachycardia. Hemodynamic variables have not convincingly
      proved to be risk factors for SCD. Therefore, this study was designed to examine
      predictors of SCD in a large number of patients with HC during long-term follow
      up periods. The relation of studied variables (clinical, electrocardiographic,
      echocardiographic, hemodynamic, and exercise test findings) to SCD in 309
      patients with HC who were initially diagnosed during 1971 through 1994 (mean
      follow-up 9.4 years) was examined by multivariate analysis. SCD occurred in 28
      patients. Independent predictors of SCD were a smaller difference between peak
      and rest systolic blood pressure during exercise testing (p=0.006), and higher
      left ventricular outflow tract pressure gradient at rest (p=0.003). Exercise
      related SCD occurred in 8 patients and exercise-unrelated SCD in 20 patients
      (mean age 28 vs 47 years, p <0.05). Thus, patients of exercise-related SCD were
      younger and had smaller increases in systolic blood pressure during exercise
      testing, whereas patients with exercise-unrelated SCD were older and had higher
      left ventricular outflow tract pressure gradient.

PMID- 9761090
TI  - Risk stratification in patients with dilated cardiomyopathy: contribution of
      Doppler-derived left ventricular filling.
AB  - Dilated cardiomyopathy (DCM) is a major cause of mortality among patients with
      heart failure. The aim of the present study was to investigate the independent
      contribution of Doppler-derived left ventricular (LV) filling to the prediction
      of survival in patients with DCM, of either ischemic or nonischemic origin, and
      to derive a simple risk stratification score based on easily available clinical
      and echocardiographic parameters. We followed 197 consecutive patients (159 men,
      mean age 60+/-13 years) with an echocardiographic diagnosis of DCM (LV end
      diastolic dimension >60 mm, fractional shortening <25%) over an average period of
      62+/-13 months. The presumed etiology of DCM was ischemic in 52% of the patients.
      During follow up, 69 patients died of cardiac causes and 41 required
      transplantation. At 5 years, overall cardiac event-free survival was 55% and
      freedom from death or heart transplantation was 43% (compared with 86% for the 5
      year age- and sex-adjusted survival rate in our country). Kaplan-Meier survival
      curves generated for different thresholds of the peak E velocity and the E/A
      ratio indicated significant worsening of prognosis with increasing values of
      these parameters in both ischemic and nonischemic patients. Using Cox stepwise
      regression analyses, age (chi-square to remove 24.4; p <0.001), peak E velocity
      (chi-square to remove=18.9; p <0.001), LV ejection fraction (chi-square to remove
      6.4; p <0.011), and systolic blood pressure (chi-square to remove 4.5; p=0.034)
      independently predicted cardiac deaths, whereas New York Heart Association (NYHA)
      functional class (chi-square to remove 48.5; p < 0.001), LV ejection fraction
      (chi-square to remove 19.1; p <0.001), E/A ratio (chi-square to remove 10.8; p
      <0.001), and systolic blood pressure (chi-square to remove 5.8; p <0.016) were
      independently associated with cardiac death or need for transplantation. Based on
      these parameters, a risk score was elaborated, which allowed appropriate
      classification of each individual patient into low- (5-year survival rate of
      72%), intermediate- (46% survival rate), and high-risk groups (11% survival
      rate). In conclusion, our data show that among the noninvasive parameters
      commonly available in patients with either ischemic or nonischemic DCM, age, the
      NYHA functional class, the LV ejection fraction, the systolic blood pressure, the
      peak E velocity, and the E/A ratio provide relevant and independent information
      regarding the risk of cardiac death or the need for heart transplantation.

PMID- 9761091
TI  - Outcome of pregnancy following intervention for coarctation of the aorta.
AB  - There are limited data regarding the outcome of pregnancy in women after
      intervention for coarctation of the aorta (CoA). The Texas Children's Hospital
      Cardiac Database was used to identify female patients with CoA born before 1980
      who had undergone balloon angioplasty or surgery. Patients with Turner's syndrome
      and cyanotic congenital heart disease were excluded. A chart review and telephone
      interview were performed. Data collected included age at intervention, type of
      intervention, the need for reintervention, functional status, number of
      pregnancies, and pregnancy outcomes. Seventy-four patients met our criteria and
      we were able to contact 52. Eighteen patients (39%) were pregnant a total of 36
      times. There were 3 spontaneous and 4 elective abortions. Preeclampsia
      complicated 4 pregnancies in 3 women (17% of primigravidas). One patient had
      systemic hypertension. Eleven infants were delivered by Cesarean section. There
      were 29 births, with an average weight of 3.0 kg. There were 5 preterm births, 4
      to a teenage mother. Only 1 child (3%) had a congenital heart defect. Thus, in
      women with an arm-to-leg blood pressure gradient of <20 mm Hg after CoA repair,
      pregnancy is successful. The occurrence of congenital heart disease in the
      offspring was 3%. Preeclampsia was similar to that in the general population.

PMID- 9761092
TI  - Nosocomial infections in coronary care units in the United States. National
      Nosocomial Infections Surveillance System.
AB  - To describe the epidemiology of nosocomial infections in Coronary Care Units
      (CCUs) in the United States, we analyzed data collected between 1992 and 1997
      using the standard protocols of the National Nosocomial Infections Surveillance
      (NNIS) Intensive Care Unit (ICU) surveillance component. Data on 227,451 patients
      with 6,698 nosocomial infections were analyzed. Urinary tract infections (35%),
      pneumonia (24%), and primary bloodstream infections (17%) were almost always
      associated with use of an invasive device (93% with a urinary catheter, 82% with
      a ventilator, 82% with a central line, respectively). The distribution of
      pathogens differed from that reported from other types of ICUs. Staphylococcus
      aureus (21%) was the most common species reported from pneumonia and Escherichia
      coli (27%) from urine. Only 10% of reported urine isolates were Candida albicans.
      S. aureus (24%) was the more common bloodstream isolate than enterococci (10%).
      The mean overall patient infection rate was 2.7 infections per 100 patients.
      Device-associated infection rates for bloodstream infections, pneumonia, and
      urinary tract infections did not correlate with length of stay, number of
      hospital beds, number of CCU beds, or the hospital teaching affiliation, and were
      the best rates for comparisons between units. Use of invasive devices was lower
      than in other types of ICUs. Overall patient infection rates were lower than in
      other types of ICUs, which is largely explained by lower rates of invasive device
      usage.

PMID- 9761093
TI  - Use of harmonic imaging without echocardiographic contrast to improve two
      dimensional image quality.
AB  - The aim of this study was to determine whether harmonic imaging (HI) improves
      endocardial visualization during 2-dimensional echocardiography without
      echocardiographic contrast. HI differs from fundamental imaging (FI) by
      transmitting ultrasound at one frequency and receiving at twice the transmitted
      frequency. This technique has been used in conjunction with contrast
      echocardiography to enhance myocardial contrast visualization. HI and FI were
      sequentially performed in 20 patients. Images were digitally stored and
      subsequently reviewed by 2 observers for the quality of endocardial
      visualization. In addition, acoustic quantification was performed in both FI and
      HI modes and endocardial tracking qualitatively judged. HI was compared with FI
      during dobutamine stress echocardiography in 17 patients who were imaged at
      baseline and peak stress. Overall, the harmonic images had less clutter and
      better myocardial blood contrast. Individual segments were better visualized with
      HI in 30% to 73% of cases. The acoustic quantification endocardial tracking was
      rated better with HI in 67% of short-axis views and in 58% of apical 4-chamber
      views. During dobutamine stress testing the overall number of interpretable
      segments improved from 64% for FI to 84% with HI. Many segments traditionally
      difficult to image were improved with HI. HI without the use of contrast agents
      improved endocardial visualization during routine 2-dimensional echocardiography.
      This improved endocardial visualization led to better endocardial tracking with
      acoustic quantification and to more segments being clinically interpretable
      during dobutamine stress testing.

PMID- 9761094
TI  - "Rescue" abciximab for complicated percutaneous transluminal coronary
      angioplasty.
AB  - We studied the in-hospital outcome of 138 consecutive patients who received
      abciximab as a "rescue" intervention for complicated coronary angioplasty in a
      high-risk clinical setting. "Rescue" treatment with abciximab was associated with
      clinical and angiographic success rates of 83% and 84%, respectively, whereas the
      risk of bleeding was higher in patients of low body weight.

PMID- 9761095
TI  - Clinical and angiographic outcome after stent placement for chronic coronary
      occlusion.
AB  - A consecutive series of 132 patients with total chronic coronary occlusions were
      compared with 1,966 patients with stenotic lesions in terms of angiographic and
      clinical outcome. We concluded that patients with chronically occluded coronary
      lesions present a higher rate of target lesion revascularizations and
      angiographic restenosis than patients with stenotic lesions.

PMID- 9761096
TI  - Myocardial Doppler velocity imaging--a quantitative technique for interpretation
      of dobutamine echocardiography.
AB  - Myocardial Doppler velocity (MDV) imaging was evaluated as a quantitative method
      for interpretation of dobutamine echocardiography by comparison with regional
      wall motion abnormalities in 70 patients with known or suspected coronary artery
      disease. Ischemic segments had the lowest increment of systolic MDV from rest to
      peak dose, and using a peak MDV of <12 cm/s to define an abnormal response, the
      sensitivity and specificity of MDV for ischemia was 86% and 96% for basal
      segments, and 81% and 89% for mid segments.

PMID- 9761097
TI  - Electrocardiographic correlates of absent septal q waves.
AB  - Compared with 100 consecutive electrocardiograms with septal q waves, 100
      consecutive electrocardiograms without septal Q waves were otherwise normal only
      4 times (vs 28 times; p <0.001). The strongest electrocardiographic correlate was
      QS in lead V1 (68 vs 4; p <0.001).

PMID- 9761098
TI  - Comparison of double bolus urokinase versus front-loaded alteplase regimen for
      acute myocardial infarction. Thrombolysis in Myocardial Infarction in Korea
      (TIMIKO) study group.
AB  - This study was performed to compare the double bolus urokinase regimen with the
      front-loaded alteplase regimen for acute myocardial infarction. Double bolus
      urokinase is an easy, safe, and effective thrombolytic regimen with comparable
      results to standard front-loaded alteplase in acute myocardial infarction.

PMID- 9761099
TI  - Increased QTc dispersion predicts lethal ventricular arrhythmias complicating
      coronary angioplasty.
AB  - This study found that increased QT dispersion just before angioplasty is an
      useful marker to predict the risk for lethal ventricular arrhythmias during
      angioplasty. The fact that successful coronary revascularization decreased QT
      dispersion suggested that a part of increased QT dispersion is related to
      myocardial ischemia.

PMID- 9761100
TI  - Impact of heart rate and atrioventricular delay on left ventricular diastolic
      filling in patients with dual-chamber pacing for sick sinus syndrome or
      atrioventricular block.
AB  - We examined the effect of left ventricular filling on different combinations of
      programmable heart rate and atrioventricular delay in patients with dual-chamber
      pacemakers. Pacing mode with heart rates of 60 beats/min and 156 ms of
      atrioventricular delay induced a diastolic pattern that resembles more than
      others the one observed in healthy subjects in sinus rhythm.

PMID- 9761101
TI  - Usefulness of intravenous metoprolol to prevent syncope induced by head-up tilt.
AB  - Intravenous metoprolol was found to be significantly more effective than placebo
      in preventing head-up tilt-table induced neurally mediated syncope. The
      reproducibility of acute tilt-table testing is only 63% and suggests caution in
      the interpretation of acute drug testing during tilt-table studies.

PMID- 9761102
TI  - A family study of anterior mitral leaflet thickness and mitral valve prolapse.
AB  - To determine whether mitral valve prolapse (MVP) with or without mitral leaflet
      thickening (> or =5 mm) represents distinct heritable conditions, 13 patients
      with MVP with leaflet thickening and their relatives were compared with 67
      patients with MVP with normal leaflets and their relatives. The 2 groups of
      relatives had similar mitral leaflet thicknesses and similar long-term outcome,
      arguing against the existence of a distinctive subtype of MVP characterized by
      increased mitral leaflet thickness.

PMID- 9761103
TI  - Results of transvenous buttoned device occlusion of patent ductus arteriosus in
      adults. International Buttoned Device Trial Group.
AB  - Examination of the immediate and follow-up results of transvenous buttoned device
      occlusion of patent ductus arteriosus suggests that the method is feasible, safe,
      and effective irrespective of the size and shape of the ductus. Although residual
      shunts are present, they tend to disappear during follow-up, and complete
      occlusion at the time of implantation may be achieved by incorporation of a
      folding plug over the button loop of the device.

PMID- 9761104
TI  - Effect of atenolol or metoprolol on arbutamine stress echocardiography in
      patients suspected of having coronary artery disease.
AB  - Arbutamine stress echocardiography was performed in 81 patients with suspected
      coronary artery disease. Arbutamine infusion, using a dedicated closed-loop
      delivery device, provided comparable myocardial stress in patients receiving beta
      1 blockers versus those who were not.

PMID- 9761105
TI  - Detecting exercise-induced ischemia in left bundle branch block using the
      electrocardiogram.
AB  - We compared 12-lead electrocardiographic changes during exercise in 41 patients
      with left bundle branch block; 7 were nonischemic and 34 had coronary artery
      obstruction > or =70% as detected by angiogram. ST depression of > or =0.5 mm
      from baseline when measured at the J point in leads II and AVF (p=0.004) and an
      increase of R-wave amplitude in lead II (p=0.05) significantly identified
      ischemia.

PMID- 9761106
TI  - Prediction of restenosis following percutaneous transluminal coronary
      angioplasty: an important but elusive goal.

PMID- 9761107
TI  - Dysfunction of the left atrium after cardioversion of atrial fibrillation.

PMID- 9761108
TI  - A senior cardiologist does not have to be a senile cardiologist.

PMID- 9761109
TI  - Dr. Howard B. Burchell is the greatest physiologic cardiologist of this century.

PMID- 9761110
TI  - Does the size of the ventricular structure differ between Down's and non-Down's
      patients, or between the Rastelli subtypes in complete atrioventricular septal
      defect?

PMID- 9761111
TI  - Plasminogen activator inhibitor-1 is an independent poor prognostic factor for
      survival in advanced stage epithelial ovarian cancer patients.
AB  - High levels of plasminogen activator inhibitor-1 (PAI-1) in tissue extracts have
      been associated with poor prognosis in many epithelial cancers. Ovarian cancers
      contain a higher concentration of PAI-1 than benign ovarian tumors or normal
      ovaries. Reports, however, on the prognostic value of PAI-1 content in ovarian
      cancers have been conflicting. We used immunohistochemistry to study the primary
      and metastatic tissues from 131 epithelial ovarian cancer cases. This group has
      been previously characterized for the expression of urokinase (uPA), uPA
      receptor, PAI-2 and macrophage colony-stimulating factor (CSF-1). The intensity
      and extent of staining for PAI-1 in the tumor epithelium was scored. Kaplan-Meier
      curves of survival were compared using the log-rank test. The Cox regression
      model was utilized for multivariate analysis. Approximately 50% of the primary
      tumors and metastases expressed PAI-1. Among invasive stages III and IV patients,
      those whose primary tumors expressed PAI-1 had a shorter overall survival. The
      combination of strong expression of PAI-1 and expression of uPA was a highly
      significant factor for short disease-free and overall survival. Similar results
      were seen with the combination of high PAI-1 and low PAI-2 expression. Strong PAI
      1 expression was significantly associated with expression of uPA receptor or CSF
      I in the tumor epithelium, but not with standard clinical parameters, and was an
      independent prognostic factor for poor survival on multivariate analysis. Our
      results show that PAI-1 expression in the primary tumor epithelium is an
      independent poor prognostic factor for survival, underscoring the tumor
      protective role of PAI-1 in ovarian cancer biology.

PMID- 9761112
TI  - Role of transforming growth factor beta3 in lymphatic metastasis in breast
      cancer.
AB  - Transforming growth factor-betas (TGFbetas) play a prominent role in tumour
      growth and metastasis by enhancing angiogenesis and suppressing immune
      surveillance. Despite the increased interest in the effect of TGFbetas on tumour
      progression, little is known about the importance of TGFbeta3 and its receptor
      CD105 in breast cancer. In the present study, we measured the plasma levels of
      TGFbeta3, CD105-TGFbeta3 complexes and TGFbeta1 in 80 patients with untreated
      early-stage breast cancer using an enhanced chemiluminescence ELISA method. Of
      the 80 patients, 14 were histologically confirmed as having axillary lymph node
      metastases, while the remainder had no evidence of lymph node involvement. The
      results showed that levels of both TGFbeta3 and CD105-TGFbeta3 complex were
      significantly elevated in patients with positive lymph nodes compared to those
      without node metastasis. Furthermore, the levels of both TGFbeta3 and CD105
      TGFbeta3 complex correlated with lymph node status. The only patient who died of
      the disease had very high plasma levels of TGFbeta3 and CD105-TGFbeta3 complex
      and positive lymph nodes; this patient developed lung metastases within 2 years
      of diagnosis. No significant correlation was seen between either TGFbeta3 or
      CD105-TGFbeta3 complex levels and tumour stage, size or histological grade.
      Plasma TGFbeta1 levels were not correlated with node metastasis, tumour stage,
      grade or size. Our data suggest that plasma levels of TGFbeta3 and CD105-TGFbeta3
      complex may be of prognostic value in the early detection of metastasis of breast
      cancer.

PMID- 9761113
TI  - Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) proteolysis in
      patients with colorectal cancer: possible association with the metastatic
      potential of the tumor.
AB  - The limited proteolysis of insulin-like growth factor (IGF)-binding protein
      (IGFBP)-3 is a key event in the regulation of endocrine bioavailability of IGFs.
      Here, we investigated IGFBP-3 and IGFBP-3 proteolysis in serum from patients with
      colorectal cancer both before and at different times following surgery. In vivo
      IGFBP-3 proteolysis, estimated by immunoblot analysis of IGFBP-3 fragments in
      serum, and in vitro IGFBP-3 protease activity of serum, estimated by a 125I-IGFBP
      3 degradation assay, allowed us to identify 2 groups of patients (IGF-M vs. IGF
      NM) with respect to their status for mobilizing the IGF system. In IGF-M
      patients, in vivo and in vitro IGFBP-3 proteolysis were significantly elevated
      (156% and 181% of the age-matched control pool, respectively) and accompanied by
      a decrease in intact IGFBP-3 (38% of the control pool). The IGFBP-3 proteolytic
      processing was further increased in response to surgical ablation of the tumor
      (mean increase 45-55%), then gradually returned to levels comparable with
      controls. In contrast, IGF-NM patients exhibited a minimal alteration of in vitro
      IGFBP-3 protease activity and even an inhibition of in vivo IGFBP-3 proteolysis,
      whereas intact IGFBP-3 was unaltered when compared with controls. Moreover, this
      pattern was not further significantly altered in response to the surgical stress.
      None (0/6) of the IGF-M patients vs. 70% (5/7) of the IGF-NM patients developed a
      metastatic disease (median duration of follow-up 26 months). Neither elevated
      amounts of pro-IGF-II nor presence of detectable IGFBP-3 protease inhibitors in
      the circulation could explain the observed suppression of IGFBP-3 proteolytic
      processing in IGF-NM patients. These results indicate that inhibition of IGFBP-3
      proteolysis and invasive properties of cancer cells are related in colorectal
      cancer patients.

PMID- 9761114
TI  - Heat shock protein expression and drug resistance in breast cancer patients
      treated with induction chemotherapy.
AB  - Heat shock proteins (Hsps) are induced in vitro by several cytotoxic drugs; in
      human breast cancer cells these proteins appear to be involved in anti-cancer
      drug resistance. The present report was designed to analyze whether chemotherapy
      affects in vivo the expression of Hsp27, Hsp70, Hsc70 and Hsp90 in breast cancer
      patients treated with induction chemotherapy and whether these proteins may be
      determinants of tumor resistance to drug administration. We have analyzed 35
      biopsies from breast cancer patients treated with induction chemotherapy.
      Expression of the Hsps in the tumors was compared with (i) histological and
      clinical responses to chemotherapy, (ii) tumor cell proliferation measured by
      proliferating cell nuclear antigen (PCNA) immunostaining and nucleolar organizer
      regions (AgNORs) staining and (iii) the expression of estrogen and progesterone
      receptors. We also compared disease-free survival (DFS) and overall survival (OS)
      with the expression of the Hsps studied. After chemotherapy, nuclear Hsp27 and
      Hsp70 expression was increased and Hsp70 and Hsc70 cytoplasmic expression was
      decreased. A high nuclear proportion of Hsp70 in tumor cells (>10%) correlated
      significantly with drug resistance. We also observed that patients whose tumors
      expressed nuclear or a high cytoplasmic proportion (>66%) of Hsp27 had shorter
      DFS. The combination of Hsp27 and Hsp70 levels showed a strong correlation with
      DFS. Neither the cellular proliferation nor the levels of steroid receptors
      showed any significant difference before or after drug administration or during
      follow-up of patients. Our results suggest that Hsp27 and Hsp70 are involved in
      drug resistance in breast cancer patients treated with combination
      chemotherapies.

PMID- 9761115
TI  - Neopterin as a prognostic parameter in patients with squamous-cell carcinomas of
      the oral cavity.
AB  - Concentrations of neopterin, which is produced by human monocytes/macrophages
      upon stimulation by interferon-gamma, were measured in urine specimens in 23
      patients with squamous-cell carcinoma of the oral cavity at diagnosis and in 12
      treated patients with the same disease when recurrence of the tumor was
      recognized. Tumor histology and routine laboratory parameters were concomitantly
      determined. Urinary neopterin values showed no statistically significant
      correlation with tumor differentiation, tumor size or patient age, but they were
      significantly higher in patients with a recurrent tumor. Patients were followed
      for up to 4 years, and the ability of all variables to predict fatal outcome was
      assessed. In univariate analysis, only neopterin (p = 0.01) and the variable
      recurrent vs. first-diagnosed tumor were significant predictors of survival. In
      multivariate analysis, a combination of neopterin (p < 0.01) and the variable
      recurrent vs. first-diagnosed tumor (p = 0.06) was found to jointly predict
      survival. Thus, urinary neopterin concentrations provide valuable prognostic
      information in patients with squamous-cell carcinoma of the oral cavity.

PMID- 9761116
TI  - The Epstein-Barr virus (EBV) major envelope glycoprotein gp350/220-specific
      antibody reactivities in the sera of patients with different EBV-associated
      diseases.
AB  - gp350 of Epstein-Barr virus (EBV) induces a strong immune response in EBV
      infected individuals, but relatively little is known about the clinical relevance
      of this response in patients with different EBV-associated malignancies and other
      diseases. Using our gp350-expressing cell clones, we studied gp350-specific
      humoral immune responses in the sera of individuals with nasopharyngeal carcinoma
      (NPC), chronic symptomatic EBV infection (CEI), Hodgkin's disease (HD), acute
      infectious mononucleosis (IM) and healthy EBV-seropositive individuals (HI). The
      titres of antibody-dependent cellular cytotoxicity (ADCC) antibodies were highest
      in HI followed by CEI, HD and NPC. EBV-neutralizing (NA) and gp350-specific IgG
      antibody profiles in these conditions were: CEI > HI > NPC > HD, whereas IgA
      titres were the highest in NPC sera followed by CEI and HD. The sera from IM
      patients were found to be negative for gp350-specific ADCC and IgA activities.
      Sera from HI were also negative for gp350-specific IgA. A significant positive
      correlation was found between serum gp350 IgA and viral capsid antigen IgA and a
      significant negative one between IgM and ADCC titres. High IgA titres were also
      found in CEI and EBV-genome positive HD in addition to NPC. Importantly, gp350
      specific IgA titres were of prognostic value in NPC patients. Our data provide
      new insights about the clinical relevance of gp350-specific immune responses in
      these diseases.

PMID- 9761117
TI  - CFTR deltaF508 carrier status, risk of breast cancer before the age of 40 and
      histological grading in a population-based case-control study.
AB  - There has been recent interest in the risk of various cancers in cystic fibrosis
      (CF) patients and carriers of cystic fibrosis transmembrane conductance regulator
      (CFTR) mutations. It has been proposed that a CFTR mutation may protect against
      breast cancer, based on evidence that elevated extracellular adenosine
      triphosphate (ATP) is known to inhibit breast cancer cell line growth and that
      CFTR pumps ATP out of epithelial cells. A CFTR mutation would therefore result in
      higher concentrations of serum ATP. A CFTR knockout mouse model had high serum
      concentrations of ATP and showed reduced breast tumour implantibility and
      decreased breast cancer growth rates. We have evaluated the relationship between
      the deltaF508 CFTR mutation and the risk of breast cancer before the age of 40.
      The deltaF508 CFTR mutation carrier rate in 272 cases (2.2%) was no different
      from the carrier rate observed in 171 controls (1.8%). If there was a protective
      effect resulting from the postulated elevation in serum ATP levels, tumours
      arising in deltaF508 CFTR carriers would have been expected to be generally less
      aggressive. When the histological features of the breast cancers with a deltaF508
      CFTR mutation were reviewed and graded using a combined architectural and
      cytological grading system, all were found to be grade III, poorly differentiated
      tumours, contrary to the predictions. A combination of our data with other large
      population-based samples of cases and controls is required to resolve this issue.

PMID- 9761118
TI  - Chromosome 5 aberrations and genetic predisposition to lung cancer.
AB  - In this study, we aimed to confirm the finding that chromosome 5 aberrations are
      predisposing factors for lung cancer. The study population consisted of 118
      previously untreated lung cancer patients and 101 healthy controls. Lymphocytes
      were treated with bleomycin for 5 hr and then allowed to recover in a drug-free
      medium for 48 hr. The mean number of cells with chromosome 5 abnormalities among
      100 cells examined was significantly higher in patients (9.12) than in controls
      (4.69) (p < 0.001). The most frequent aberration was a 5q deletion and the
      breakpoints clustered at the 5q13-5q31 region. We then dichotomized the number of
      induced chromosome 5 abnormalities in peripheral blood lymphocytes by the 75th
      percentile in that of the controls. 103 (87.3%), of the 118 patients, but only 31
      (30.7%) of the 101 controls, exhibited induced breaks above this point. After
      adjustment for age, sex, ethnicity and smoking status, we found that the
      sensitive group was at 14.4-fold increased risk for lung cancer. There was also a
      significant (p < 0.01) gradient of increased risk for lung cancer with an
      increasing number of chromosome 5 lesions. Therefore, chromosome 5 lesions,
      especially those at 5q, may be a molecular target of carcinogens in the
      development of lung cancer.

PMID- 9761119
TI  - Quantitative analysis of p53 protein in non-small cell lung cancer and its
      prognostic value.
AB  - Accumulation of mutant p53 protein occurs frequently in human malignancies,
      including 40-60% of non-small cell lung carcinomas. The implications of such p53
      over-expression, usually assessed by immunohistochemical techniques, for the
      prognosis of lung cancer patients remain undetermined. In this study, we used a
      time-resolved immunofluorometric assay to measure p53 protein concentrations in
      extracts prepared from 86 primary non-small cell lung tumours and examined the
      associations between p53 protein levels (corrected for total protein) and other
      clinico-pathologic variables, including post-surgical disease-free and overall
      survival. Contingency tables analysed by chi2 tests revealed no significant
      relationships between p53 status, defined by a median cut-off point, and patient
      gender, age, disease stage, histologic grade and type, lymph node extension,
      smoking history and administration of adjuvant chemotherapy or radiation.
      However, multivariate Cox proportional hazard regression analysis demonstrated a
      dose-response relationship between p53 concentration, expressed as a 4-level,
      quartile-divided variable, and increased risk of relapse (p = 0.010) and death (p
      = 0.016). Patients whose tumours contained p53 concentrations exceeding the
      median value had over 3-fold higher risk of relapse (p = 0.002) and death (p =
      0.007) than those whose tumours had lower p53 concentrations. We also provide
      evidence suggesting that the impact of p53 on survival is greater in patients
      with squamous cell carcinoma than in those with adenocarcinoma. Although the
      latter finding needs confirmation, our results suggest that application of an
      immunoassay of p53 protein on non-small cell lung tumour extracts may identify
      patients at increased risk of unfavourable outcome.

PMID- 9761120
TI  - Osteopontin expression in a group of lymph node negative breast cancer patients.
AB  - The aim of this study was to examine the cellular distribution of osteopontin
      (OPN) protein [by immunohistochemical (IHC) analysis] and mRNA [by in situ
      hybridization (ISH)] in the primary tumors of lymph node negative (LNN) breast
      cancer patients and to determine whether the level of immunodetectable OPN may be
      associated with tumor aggressiveness. We examined OPN levels in tumors from 154
      patients with LNN breast cancer who were followed for a median of 7 years (range
      1.7-16.3 years). IHC staining for OPN was seen in tumor infiltrating macrophages
      and lymphocytes in 70% of these tumors, and in the carcinoma cells themselves in
      26%. ISH was performed to determine cellular distribution of OPN mRNA expression
      in sections from selected tumors. OPN mRNA was detected in groups of tumor cells,
      individual tumor cells and tumor infiltrating macrophages and lymphocytes.
      Matched sections showed that some tumor cells with IHC staining for OPN protein
      were also positive for OPN mRNA by ISH, in contrast with previous studies which
      have shown OPN mRNA expression only in tumor infiltrating inflammatory cells. Our
      results thus indicate that OPN protein can be produced by breast cancer cells in
      vivo and suggest that it may also be taken up from the environment (i.e.,
      secreted by inflammatory cells or other tumor cells). Tumor cell IHC staining
      intensity was then assessed using a semiquantitative scoring system. Univariate
      analysis showed tumor cell OPN positivity above an optimized cutpoint to be
      significantly associated with decreased disease-free survival (DFS) and overall
      survival (OS). The results of this pilot study thus suggest that the ability of
      breast cancer cells to either synthesize OPN or to bind and sequester OPN from
      the microenvironment may be associated with tumor aggressiveness and poor
      prognosis.

PMID- 9761121
TI  - Transmembrane 4 superfamily as a prognostic factor in pancreatic cancer.
AB  - Several members of the transmembrane 4 superfamily (TM4SF) have been reported to
      be related to tumor progression and metastasis. The aims of our study were to
      clarify the relationship between TM4SF and pancreatic cancer and to determine the
      prognostic significance of TM4SF in human pancreatic cancer. The mRNA levels for
      MRP-1/CD9, KAI1/CD82 and ME491/CD63, which belong to the TM4SF gene family, were
      evaluated in 40 resectable pancreatic adenocarcinomas using reverse transcriptase
      PCR. MRP-1/CD9 gene expression was associated with lymph node status, and with
      pathological status. Moreover, MRP-1/CD9 expression was inversely associated with
      histo-pathological grading. KAI1/CD82 gene expression was inversely associated
      with tumor status. ME491/CD63 gene expression, however, was conserved in all
      pancreatic cancers. The overall survival rate for the 22 patients whose tumors
      had decreased MRP-1/CD9 gene expression was strikingly lower than that for the 18
      patients with MRP-1/CD9-positive tumors. The overall survival rate of the 15
      patients who were KAI1/CD82-positive was significantly higher than that of the 25
      patients with decreased KAI1/CD82 gene expression. In a multivariate analysis
      using the Cox proportional hazards model, MRP-1/CD9 and KAI1/CD82 status was
      found to be the most significant.

PMID- 9761122
TI  - Association between genetic polymorphisms of glutathione S-transferase P1 and N
      acetyltransferase 2 and susceptibility to squamous-cell carcinoma of the
      esophagus.
AB  - We examined the effect of genetic polymorphisms of phase-II enzymes, glutathione
      S-transferase P1 (GSTP1) and N-acetyltransferase2 (NAT2) on susceptibility to
      esophageal squamous-cell carcinoma To determine the genotypes of the 2
      polymorphisms, PCR-based analysis was performed on samples from 66 Japanese
      patients who had been histologically diagnosed as having esophageal squamous-cell
      carcinoma, and 164 healthy Japanese controls. The frequency of the AA genotype of
      GSTP1 was significantly higher in esophageal-cancer patients than in the controls
      according to logistic-regression analysis (92% of the patients and 68% of the
      controls; odds ratio (OR), 8.0; p = 0.0013). Also, more patients had the slow and
      intermediate acetylator genotypes of NAT2 than the controls (15% and 38% vs. 10%
      and 32% respectively; OR of the slow acetylator genotype, 4.2; p = 0.032; OR of
      the slow plus intermediate acetylator genotypes, 2.9; p = 0.015). Polymorphisms
      of GSTP1 and NAT2 may serve as genetic biomarkers for predicting susceptibility
      to esophageal squamous-cell carcinoma.

PMID- 9761123
TI  - Cox multivariate regression models for estimating prognosis of patients with
      endometrioid adenocarcinoma of the uterine corpus who underwent thorough surgical
      staging.
AB  - The International Federation of Gynecology and Obstetrics (FIGO) adopted surgical
      staging criteria in 1988. Many studies have shown that histologic grade, nuclear
      grade, lymph-vascular space invasion and cell type are also important predictors
      of survival. It has not been clarified, however, how to integrate these
      histopathologic variables into the process of estimating individual prognosis. We
      performed Cox multivariate regression analysis to create models that incorporate
      various histopathologic factors for estimating the prognoses of patients with
      endometrioid adenocarcinoma of the uterine corpus. Our study was based on data
      from 206 patients who underwent complete surgical staging, including systematic
      pelvic and para-aortic lymph node dissection. Two models resulted: one included
      depth of myometrial invasion, para-aortic node metastasis and the number of sites
      involved by the tumor among the cervix, ovary and pelvic lymph nodes (which we
      designated as extracorporeal spread score, ECS) and the other incorporated
      nuclear grade and lymph-vascular space invasion as variables. These 2 models
      enabled the prognosis for patients with endometrioid adenocarcinoma to be
      stratified into several levels according to hazard ratio. Comprehensive
      integration of the histopathologic prognostic factors, categorized into those
      relating to tumor extent and those relating to tumor virulence, should facilitate
      the estimation of individual prognosis more accurately than FIGO staging alone.

PMID- 9761124
TI  - Distribution pattern and risk factors of pelvic and para-aortic lymph node
      metastasis in epithelial ovarian carcinoma.
AB  - The distribution of lymph node metastasis and the clinicopathologic risk factors
      for nodal involvement in ovarian carcinoma need to be clarified based on
      systematic lymph node dissection. We studied 115 patients with ovarian carcinoma
      who underwent systematic pelvic and para-aortic lymph node dissection between
      1987 and 1997. The incidence and distribution of lymph node metastasis are
      described and the clinico-pathologic risk factors for nodal involvement are
      investigated. Based on the occurrence of lymph node metastasis in the early
      stages, the incidence of solitary node involvement and the distribution of lymph
      node metastasis, we conclude that the primary site of nodal involvement in
      ovarian carcinoma is the para-aortic node (PAN), especially PAN superior to the
      inferior mesenteric artery (IMA). By univariate analysis, clinical stage,
      histologic type (mucinous vs. others), grade, multiple peritoneal metastases,
      peritoneal cytology, volume of ascites and serum CA125 level were correlated with
      overall incidence of lymph node metastasis. By performing a multivariate analysis
      with the clinical stage excluded, it was revealed that grade and peritoneal
      cytology were independent factors for PAN metastasis (p < 0.0025 and < 0.001,
      respectively) and that multiple peritoneal metastases and PAN metastasis were
      significant predictors of pelvic node metastasis (p < 0.01 and < 0.005,
      respectively). In conclusion, the PANs superior and inferior to IMA should be
      explored in staging of ovarian carcinoma that appears to be confined to the
      ovaries. To determine accurately the extent of disease, both the para-aortic and
      pelvic areas may need to be sampled or dissected in the case of ovarian carcinoma
      involving the peritoneal surfaces.

PMID- 9761125
TI  - Carcinomas of the renal pelvis associated with smoking and phenacetin abuse: p53
      mutations and polymorphism of carcinogen-metabolising enzymes.
AB  - Phenacetin abuse and smoking are established risk factors for transitional cell
      carcinomas of the urinary tract. In the present study, we analysed exposure and
      the clinical course of patients who underwent nephrectomy for transitional cell
      carcinoma of the renal pelvis. PCR-SSCP of archival, paraffin-embedded
      histological sections followed by direct DNA sequencing revealed that 29 of 89
      (33%) renal pelvic carcinomas contained a p53 mutation. Double mutations were
      found in 4 tumours and triple mutations in 1 tumour. The incidence of p53
      mutations was significantly higher in tumours with grades 3 and 4 than in those
      with grades 1 and 2 and higher in invasive than in non-invasive tumours.
      Furthermore, patients with carcinomas carrying a p53 mutation showed poorer
      survival than those without mutation. The type of p53 mutation in renal pelvic
      carcinomas was similar to that reported for bladder cancer, G:C-->A:T transition
      mutations being most frequent (45%, 33% of these at CpG sites), followed by G:C-
      >T:A and G:C-->C:G transversions. The incidence and type of p53 mutation did not
      differ significantly in patients with a history of phenacetin abuse, smoking or
      neither of these habits. This was also true for G:C-->T:A transversions (17.5% of
      mutations), which are considered typical of smoking-induced carcinomas at other
      sites, e.g., lung, oral cavity and oesophagus. Our results indicate that the
      frequency and pattern of p53 mutations are similar in transitional cell
      carcinomas of the bladder and the renal pelvis and do not reflect exposure to
      phenacetin and/or smoking. The frequency of genetic polymorphism in genes coding
      for carcinogen-metabolising enzymes (CYP1A1, NAT1, GSTT1 and GSTM1) was also
      independent of exposure. Although the sample size of our study does not allow
      definite conclusions, these data are compatible with chronic tissue damage as a
      causative factor in the evolution of urothelial carcinomas rather than pointing
      to a direct mutagenic effect of phenacetin and tobacco-specific carcinogens.

PMID- 9761126
TI  - Prognostic value of RET proto-oncogene point mutations in malignant and benign,
      sporadic phaeochromocytomas.
AB  - Somatic mutations in the RET proto-oncogene are involved in the pathogenesis of
      an important subset (40-60%) of sporadic medullary thyroid carcinomas (MTCs) and
      less frequently (0-31%) in benign, sporadic phaeochromocytomas. Since limited
      data exist regarding the significance of somatic RET mutations in malignant
      phaeochromocytomas, we analysed a multicentre series of proven malignant (i.e.,
      metastasised) phaeochromocytomas. Analogous with MTCs, where RET mutations lead
      to an aggressive behaviour, we hypothesised that somatic mutations would occur
      more frequently in malignant than in benign phaeochromocytomas. Paraffin-embedded
      tissue was available from 29 malignant and 27 benign phaeochromocytomas. Exons
      10, 11 and 16 were analysed by non-radioactive single-strand conformation
      polymorphism, heteroduplex gel electrophoresis, restriction enzyme digestion and
      aberrant band patterns by non-isotopic sequencing. In only 1 of 29 malignant
      phaeochromocytomas was a mis-sense mutation found (at codon 634 of exon 11),
      whereas in 15% (4/27) of the benign tumours a point mutation was detected (in 3
      tumours in exon 16 at codon 918 and in 1 tumour in exon 10 at codon 618). Absence
      of these mutations in non-tumourous DNA proved their somatic origin. Contrary to
      what has been reported for MTCs, oncogenic RET mutations are not associated with
      an aggressive tumour behaviour in sporadic phaeochromocytomas.

PMID- 9761127
TI  - Cytosol concentrations of CD44 isoforms in breast cancer tissue.
AB  - The role of the adhesion molecule CD44 in the natural history of breast cancer is
      controversial. We investigated the CD44 isoform CD44v5 and CD44v6 concentrations
      in the cytosol of 90 breast cancer specimens, 9 fibroadenomas and 22 normal
      breast tissue specimens by means of ELISA. CD44v5 and CD44v6 cytosol
      concentrations were statistically significantly higher in breast cancer compared
      with fibroadenoma and normal breast tissue (Mann-Whitney U-test, p = 0.009 and p
      < 0.001, respectively). When CD44 isoforms were correlated with lymph node
      involvement, histological grading, histological type, tumor stage and age at
      diagnosis, we found no statistically significant correlation with any of the
      investigated clinico-pathological parameters. In univariate and multivariate
      analyses, CD44v5 and CD44v6 were of no prognostic relevance regarding disease
      free survival in breast cancer patients (log-rank test, p = 0.16 and p = 0.08,
      respectively). Our results indicate that CD44 isoforms are increased in samples
      from tumors relative to normal tissue. Our data show that CD44v5 and CD44v6
      isoform expression, although up-regulated by malignant transformation, is not
      required to acquire a metastatic phenotype in breast cancer. Furthermore, our
      data support the assumption that cytosolic CD44 isoforms are of no prognostic
      relevance for disease-free survival of breast cancer patients.

PMID- 9761128
TI  - Cytoplasmic accumulation of alpha-catenin is associated with aggressive features
      in laryngeal squamous-cell carcinoma.
AB  - Aberrations in the function of alpha-catenin (alpha-cat), the anchoring protein
      of E-cadherin, are believed to cause dysfunction of the cadherin-catenin complex,
      leading to disturbed cell-cell adhesion. It has been suggested that expression of
      alpha-cat in human tumours might be a better indicator of aggressive phenotype
      than expression of E-cadherin. The value of alpha-cat as a prognostic marker in
      laryngeal squamous cell carcinoma (LSCC) is unclear. To determine the potential
      prognostic significance of alpha-cat, paraffin-embedded samples from 159 patients
      with invasive carcinoma left in the section and with long-term follow-up were
      evaluated immuno-histochemically for alpha-cat expression, and the results were
      related to histopathological grade, tumour stage and survival. Two patterns of
      staining were observed: pure membranous staining (57%) and membranous staining
      with cytoplasmic involvement (43%). Cytoplasmic involvement of alpha-cat was
      associated with dedifferentiation, advanced tumour stage and nodal status. In
      addition, supra-glottic tumours showed more often cytoplasmic involvement of
      alpha-cat than glottic tumours. Patients with cytoplasmic involvement appeared to
      have a trend towards poor overall survival, though without statistical
      significance. These results suggest that cytoplasmic involvement of alpha-cat is
      associated with aggressive behaviour and metastatic phenotype of LSCC.

PMID- 9761129
TI  - Assessment of peripheral nerve function in an Ecuadorian rural population exposed
      to pesticides.
AB  - To explore the peripheral nervous system effects of regular agricultural
      pesticide use, a cross-sectional survey was conducted in highland Ecuador.
      Participants were 144 occupationally exposed farm members, 30 female farm members
      with little direct exposure, and 72 unexposed local town residents, frequency
      matched to the exposed people on age, sex, and education. Organophosphorus and
      carbamate insecticides and dithiocarbamate fungicides accounted for the majority
      of pesticide applications, with leaking backpack sprayers, minimal use of
      personal protective equipment, and frequent dermal contact being the norm. In
      polytomous logistic regression analyses, applicators had significantly greater
      odds for more current peripheral nerve symptoms (odds ratio OR = 3.1), signs of
      poor coordination (OR = 4.3), abnormal deep tendon reflexes (OR = 2.9), and
      reduced power (OR = 2.1) compared to controls. Mean toe vibration threshold
      scores, on a logarithmic scale, were significantly higher among applicators (beta
      = 0.035) and those reporting previous pesticide poisonings (beta = 0.074). Such
      indicators of peripheral nervous system effects may be due to a variety of
      factors, including high pesticide exposure conditions.

PMID- 9761130
TI  - Comparison of the effects of iodine and iodide on thyroid function in humans.
AB  - Concerns have been raised over the use of iodine for disinfecting drinking water
      on extended space flights. Most fears revolve around effects of iodide on thyroid
      function. iodine (I2) is the form used in drinking-water disinfection. Risk
      assessments have treated the various forms of iodine as if they were
      toxicologically equivalent. Recent experiments conducted in rats found that
      administration of iodine as I- (iodide) versus I2 had opposite effects on plasma
      thyroid hormone levels. I2-treated animals displayed elevated thyroxine (T4) and
      thyroxine/triiodothyronine (T/T3) ratios, whereas those treated with I- displayed
      no change or reduced plasma concentrations of T4 at concentrations in drinking
      water of 30 or 100 mg/L. The study herein was designed to assess whether similar
      effects would be seen in humans as were observed in rats. A 14-d repeated-dose
      study utilizing total doses of iodine in the two forms at either 0.3 or 1 mg/kg
      body weight was conducted with 33 male volunteers. Thyroid hormones evaluated
      included T4, T3, and thyroid-stimulating hormone (TSH). TSH was significantly
      increased by the high dose of both I2 and I-, as compared to the control.
      Decreases in T4 were observed with dose schedules with I- and I2, but none were
      statistically significant compared to each other, or compared to the control.
      This human experiment failed to confirm the differential effect of I2 on
      maintenance of serum T4 concentrations relative to the effect of I- that was
      observed in prior experiments in rats. However, based on the elevations in TSH,
      there should be some concern over the potential impacts of chronic consumption of
      iodine in drinking water.

PMID- 9761131
TI  - Cytokine production by C57BL/6 mouse spleen cells is selectively reduced by
      exposure to propanil.
AB  - Numerous immunomodulatory effects are caused by propanil, an extensively used
      postemergent herbicide. The T-dependent antibody response is suppressed after
      exposure to propanil, raising the question of propanil's effect on T-helper-cell
      populations. In the present study, we show that the production of several T-cell
      cytokines is affected by propanil after in vivo or in vitro exposure. In vivo
      exposure to propanil caused the reduction of interleukin (IL)-2, IL-6,
      granulocyte-macrophage colony-stimulating factor (GM-CSF), and interferon (IFN)
      gamma production in concanavalin A-stimulated spleen cell cultures established 2
      d after exposure. IFN-gamma and GM-CSF production had recovered by d 4
      postexposure; however, IL-2 and IL-6 levels continued to be depressed through d 7
      postexposure. Continuous in vitro treatment of normal spleen cells with propanil
      decreased IL-2, IL-6, GM-CSF, and IFN-gamma production after concanavalin A
      activation. Pulsing normal spleen cell cultures with propanil for up to 8 h
      before T-cell activation resulted in reduced IL-6 but not IL-2 or IFN-gamma
      production. These data indicate that propanil can selectively inhibit spleen cell
      cytokine production, which could contribute to the immunomodulatory effects
      previously described.

PMID- 9761132
TI  - Modulation of proto-oncogene expression by polychlorinated biphenyls in 3T3-L1
      cell line.
AB  - The effects of two substituted polychlorinated biphenyls, the 3,4,5,3',4,5' (PCB
      169) and the 2,3,4,2',4',5' (PCB-138) forms, were examined on the expression of c
      myc, c-jun, c-ras, and jun-b in 3T3-L1 cells. Northern blot analysis demonstrated
      that the two PCBs, which exhibit a coplanar and di-ortho-substituted
      configuration, activated these oncogenes differently. PCB-138 markedly induced
      overexpression of ras, jun, and myc, whereas PCB-169 led to the overexpression of
      jun-b. High-performance liquid chromatography analysis of the cell samples
      treated in medium without serum revealed a higher intracellular concentration of
      the 2,3,4,2',4',5'-hexachlorobiphenyl (hexaCB), whereas the 3,4,5,3',4'5'-hexaCB
      reached the same concentration in the sonicated samples of cells with or without
      serum. These results indicated that there was a relationship between PCB
      structure, bioavailability, and the capacity to stimulate oncogene expression.

PMID- 9761133
TI  - Subchronic toxicity of benzothiophene on rats following dietary exposure.
AB  - The systemic and neurobehavioral effects of benzo[b]thiophene (routinely referred
      to as benzothiophene) were studied in rats following 13-wk oral exposure. Male
      (170 +/- 16 g) and female (146 +/- 12 g) Sprague-Dawley rats (10 animals per
      group) were fed diet containing 0.5, 5, 50, or 500 ppm benzothiophene for 13 wk.
      Control animals were given rat feed plus vehicle (corn oil) only. No clinical
      signs of toxicity and neurobehavioral effects were observed using screening tests
      that included cage-side observations, righting reflex, open field activities, and
      forelimb and hindlimb grip strength. Elevated serum aspartate aminotransferase
      activity and bilirubin level were observed in highest dose females. Except for a
      statistically significant decrease in hematocrit in the highest dose males,
      benzothiophene exerted no marked effects on hematological parameters.
      Benzothiophene exposure did not result in alterations in hepatic alkaline
      phosphatase activity, or the typical hepatic phase I (aniline hydroxylase,
      ethoxyresorufin O-deethylase, pentoxyresorufin O-dealkylase, aminopyrine N
      demethylase) and phase II (UDP-glucuronosyltransferase, glutathione S
      transferase) drug-metabolizing enzyme activities. No significant elevation in
      urinary ascorbic acid, protein, and N-acetylglucosaminidase activity was detected
      in the treated animals. Peribiliary fibrosis was the most significant
      histological change and occurred in the liver of females in the 50 and 500 ppm
      groups. Mild epithelial hyperplasia in the renal pelvis was detected in the
      majority of 5 and 50 ppm females, with epithelial hyperplasia in the urinary
      bladder observed in the 50 ppm females. In males, increased incidence and
      severity of mild binucleation of hepatocytes and mild thickening of the basement
      membrane in kidney cortex were observed at 500 ppm. Benzothiophene was not
      detected in the urine of high-dose animals at the termination of the experiment.
      Based on the kidney, hepatic, and hematocrit changes, the no-observed-adverse
      effect level (NOAEL) in the diet was determined to be 0.5 ppm (0.04 mg/kg/d) for
      females and 50 ppm (3.51 mg/kg/d) for males.

PMID- 9761134
TI  - Modulation of metal-induced cytotoxicity by maillard reaction products isolated
      from coffee brew.
AB  - Nondialyzable Maillard reaction products (MRPs) were recovered from three
      different coffee brew extracts (i.e., brewed, boiled, instant) to evaluate the
      efficacy of MRPs in modulating in vitro metal-induced cytotoxicity in C3H/10T1/2
      mouse embryo fibroblast cells, cultured in the presence of Fe2+, Fe3+, or Cu2+
      ions. Preliminary experiments were performed in an vitro linoleic acid emulsion
      model system to characterize the anti- or pro-oxidant activity of coffee MRPs.
      Cytotoxicity experimental protocols involved both the direct application of metal
      ions and coffee MRPs to fibroblast cells, and the premixing of metal ions with
      coffee MRPs at room temperature prior to incubating with fibroblast cells. Fe2+
      and Cu2+ significantly lowered the colonization efficiency (CE) of cells at all
      three concentrations (i.e., 0.1, 10, 50 microM) used. Similar Fe3+ activity was
      observed only at 50 microM concentration. None of the coffee MRPs alone or
      together with 0.1 and 10 microM of Fe2+ or Fe3+ produced cytotoxic effects during
      direct application. The premixing step, however, significantly enhanced the CE of
      cells compared to the control, denoting cytoprotection, only in the presence of
      Fe2+. In addition, the application of MRPs with 0.1 or 10 microM of Cu2+
      significantly lowered the CE of cells than the control, but enhanced the CE of
      cells than the Cu2+ added control. These results corresponded directly with the
      results of model linoleic acid emulsion test, thereby demonstrating that lipid
      hydroperoxide generation is the source for fibroblast cell toxicity when MRPs are
      added to cells together with metal ions. These results further indicate that
      coffee MRPs can suppress in vitro metal-induced cytotoxicity to a certain extent
      when Fe2+, Cu2+, or Fe3+ ions are present below a concentration of 50 microM,
      possibly by chelating the metal ions. Ionic reducing capacity of coffee MRPs,
      albeit small, may explain the potential for increased cytotoxicity at higher
      coffee MRP concentrations.

PMID- 9761135
TI  - Publication bias in nursing research.

PMID- 9761136
TI  - Extended care referral after hospital discharge.
AB  - The purpose of this study was to describe the influence of selected
      organizational and medical factors on communication between hospitals and
      extended care facilities (ECF) in the referral of elderly clients following
      discharge from acute care. Using a tool with previously established reliability
      and validity, 455 closed records of referral were purposively selected and
      reviewed for the amount and type of information an ECF received upon referral, as
      well as selected organizational and medical factors. Hospitals transferred
      approximately three-fourths of the patient care data recommended in the
      literature. Information contained in an ECF referral consisted primarily of
      background and medical data, with some nursing care data and limited psychosocial
      data. More information-rich referrals were generated by very large hospitals and
      by specialty care units. Similarly, proprietary ECFs received more patient care
      data than their not-for-profit counterparts. Research concerning patient care
      communication between provider organizations across the health care delivery
      system may assist nurses in developing better patient care information-management
      systems.

PMID- 9761137
TI  - Development and evaluation of the Osteoporosis Self-Efficacy Scale.
AB  - The Osteoporosis Self-Efficacy Scale was developed as a measure of self-efficacy,
      or confidence, for behaviors related to physical activity and calcium intake. An
      item pool of 21 statements, responded to on a visual analog self-report format,
      was reviewed by a panel of expert judges. The revised item stems were tested with
      a sample of 201 women, ages 35 to 95. Concurrent data on sport, leisure, and
      exercise activity and calcium in diet and dietary supplements were collected from
      the respondents. Factor analysis of responses to the self-efficacy items revealed
      a logical, theoretically meaningful two-factor structure, one for physical
      activity and one for calcium intake. Internal consistency estimates for each of
      the two factors were in the .90s. Convergent and discriminant validity analyses
      as well as hierarchical regression analyses to explain self-reports of physical
      activity and calcium intake were supportive. The final version of the brief,
      psychometrically sound scale contains items reflecting initiation, maintenance,
      and persistence at osteoporosis preventive behaviors; thus, the Osteoporosis Self
      Efficacy Scale is a potentially beneficial research instrument.

PMID- 9761138
TI  - The impact on quality of life of patient-related barriers to pain management.
AB  - A stress-coping model of relationships between patients' beliefs about pain,
      coping (analgesic use), pain severity, analgesic side-effects, and three quality
      of life (QOL) outcomes was tested. Participants were 182 men and women with
      cancer who completed valid and reliable self-report measures of relevant
      variables. Antecedent variables (age and education) showed expected relationships
      with beliefs. As predicted, beliefs were significantly related to analgesic use.
      Analgesic use was inversely related to pain severity, but was not related to side
      effect severity. Analgesic use was inversely related to impairments in QOL before
      controlling for pain and side-effect severity, but not after these two variables
      were controlled. Both analgesic side-effects and pain severity were related to
      impaired QOL outcomes, including difficulty performing life activities, depressed
      mood, and poor perceived health status.

PMID- 9761139
TI  - A causal model of voluntary turnover among nursing personnel in long-term
      psychiatric settings.
AB  - Causal modeling was used to explore the processes by which individual
      characteristics, job satisfaction, and intention to quit explain turnover among
      nursing personnel in 29 Department of Veterans Affairs (VA) long-term psychiatric
      settings. The sample consisted of 1,106 registered nurses (RNs), licensed
      practical nurses (LPNs), and nurses' aides. We conceptualized turnover as a
      multistage process linking social and experiential orientations, attitudes toward
      the job, the decision to quit, and the behavior of actually quitting. Intention
      to quit was the strongest direct predictor of turnover. Professional growth
      opportunities and workload were important indirect predictors of turnover.
      Dissatisfaction with work hazards and relationships with coworkers were both
      indirect and direct predictors of turnover. Attitudes towards the job varied by
      nursing group. LPNs and aides were less satisfied than RNs with autonomy and work
      hazards. RNs were more dissatisfied with workload. We conclude that strategies to
      promote retention need to address aspects of jobs tailored to specific nursing
      groups.

PMID- 9761140
TI  - Australian nurses' experiences and attitudes in the "Do Not Resuscitate"
      decision.
AB  - The effects of Australian nurses' (n=285) awareness of a "Do Not Resuscitate"
      (DNR) policy and various practice settings on the DNR decision were examined. A
      questionnaire, developed by the investigator, was used to gauge nurses'
      experiences and attitudes in DNR practice. Decision making was not significantly
      affected by nurses' awareness of a DNR policy in hospitals where a policy was
      present. Although nurses believed that the patient, next-of-kin, and nurse should
      play a predominant role in the DNR decision, medical staff were usually
      responsible for the decision. Various strategies are suggested as to how nurses
      could make a greater impact on the DNR decision.

PMID- 9761141
TI  - Decision-making models in different fields of nursing.
AB  - The purpose of this study was to identify the decision-making models used by
      nurses in different fields of nursing and to find out which variables explain the
      use of those models. The instrument for the project was developed on the basis of
      existing decision-making theories and earlier studies on nurses' decision making.
      The sample consisted of 483 Finnish nurses from five fields of nursing: long-term
      care, short-term medical-surgical care, critical care, health care, and
      psychiatric care. The statistical analyses consisted of factor analysis, factor
      scores, and correspondence analysis. Five different models of nursing decision
      making were identified. The nature of the nursing task and the nursing context
      showed associations with decision making on all models. The structure of
      knowledge and nurses' practical experience did not provide an explanation for
      nurses' decision making on any model.

PMID- 9761142
TI  - Development of the Rural-Urban Demand Indicator (RUDI).
AB  - In this article we describe development of RUDI (Rural-Urban Demand Indicator), a
      multivariate interval level measure of demand for health services. RUDI ranks
      counties by population and purchasing power and was developed for use in a wide
      variety of health-related research and for policy analyses. RUDI is based on
      microeconomic theory and Grossman's (1972) extension of the theory, that the
      family produces health and that the family's demand for health services is
      derived from the demand for health. Two factors define RUDI: DEMOS (demographics)
      and EWB (economic well-being). These two factors accounted for 66.2% of the
      variance observed in 1990 census data. A variety of other analyses offer evidence
      of known- groups, convergent, factorial, and predictive validity.

PMID- 9761143
TI  - The call to experts in qualitative research.
AB  - There are many researchers engaged in qualitative research who look to experts in
      this mode of inquiry to validate their findings. But can any outsider, even an
      "expert" in qualitative research, do this? Such an expert is unlikely to know the
      data as well or to be as fully immersed in the project as the researcher. There
      are different kinds of expertise that may be required for different phases and
      purposes of research, and to satisfy different epistemological and ethical
      concerns. Moreover, new modes of participatory research have complicated the role
      of expert and the idea of expertise. Researchers must be judicious in their
      claims to expert validation, and experts must move researchers away from a
      preoccupation with validation toward craftsmanship and accountability to diverse
      communities.

PMID- 9761144
TI  - Management of the abnormal cervical smear and a historical review of cone biopsy
      in Victoria.

PMID- 9761145
TI  - Diagnosis and treatment of cervical intraepithelial neoplasia in a single visit.
AB  - We evaluated the diagnostic and therapeutic efficacy of large loop excision of
      the transformation zone (LLETZ) performed in the first visit (see and treat
      policy) as compared to LLETZ treatment performed as an interval procedure. Data
      of 248 patients were analyzed of which 206 patients had LLETZ. Two thirds of the
      procedures were performed at the first visit. Of all the women who had the 'see
      and treat policy' 94.9% were diagnosed to have cervical intraepithelial neoplasia
      (CIN) on histology compared to 90.8% in the interval treatment group. A total of
      3 (1.4%) patients were detected to have microinvasive carcinoma. There was no
      difference in the immediate postoperative complication rate, overtreatment rate
      and need of repeat treatment in both the groups. Single visit colposcopy and loop
      treatment is a safe and effective option for treatment of cervical epithelial
      abnormalities. The experience of the colposcopist is very important.

PMID- 9761146
TI  - The use of large loop excision of the transformation zone in management problems
      of cervical intraepithelial neoplasia.
AB  - We studied 2 groups of women whose management is controversial: those with
      cervical intraepithelial neoplasia (CIN) grade 2 or 3 on smear, but only CIN
      grade 1 or no abnormality on target biopsy (Group 1), and those with persistent
      CIN grade 1 on smear and up to CIN 1 on biopsy (Group 2). We set out to assess
      whether large loop excision of the transformation zone (LLETZ) was an acceptable
      method of treating these 2 groups of women. A review of 100 consecutive patients
      was undertaken. There were 71 women in Group 1 and 29 women in Group 2. The LLETZ
      procedures were performed under local analgesia and no immediate problems were
      encountered. Delayed haemorrhage requiring vaginal packing and admission to
      hospital occurred in 1 patient. In Group 1, histopathology of the LLETZ biopsies
      showed CIN 2 or 3 in 29 (40.8%) of the women, CIN 1 in 24 (33.8%) and no CIN in
      18 (25.3%), and in Group 2, CIN 2 or 3 was seen in 5 (17.2%) of the women, CIN 1
      in 11 (37.9%) and no CIN in 13 (44.8%). At 12 months completed follow-up, 4
      patients in Group 1 had recurrent CIN 1 or equivocal CIN 1 and 1 patient from
      Group 2 had recurrent CIN 1, giving an overall recurrence rate of 5 of the 94
      patients who completed follow-up (5%). We concluded that LLETZ was a useful
      procedure in both groups. In Group 1 the provision of a histological diagnosis on
      the LLETZ biopsy was a check on the accuracy of the cervical smear report. In
      Group 2, LLETZ offered the advantage of rapidly returning the smear to normal in
      most patients, and the diagnosis and treatment of those women who actually had a
      high-grade lesion.

PMID- 9761147
TI  - High prevalence of chlamydia and Pap-smear abnormalities in pregnant adolescents
      warrants routine screening.
AB  - A prospective cohort of pregnant adolescent patients who planned to deliver at 1
      of 3 Perth metropolitan hospitals was studied; 1 subgroup of this cohort was
      offered universal screening for cervical chlamydial infection and Pap-smear
      abnormalities (screened), and the remainder of the cohort were offered screening
      at the discretion of the attending medical staff (control). High prevalences of
      both chlamydial infection (27%) and Pap-smear abnormalities (38%) were detected
      in the screened cohort. The majority of Pap-smear abnormalities were inflammatory
      atypia, but high-grade Bethesda lesions were also diagnosed. In the control
      group, the prevalence of positive swabs and abnormal Pap-smear reports in those
      tested was also high (22% and 35% respectively), but significantly fewer patients
      were tested (18% and 33% respectively in the control group, compared to 92% and
      94% in the screened group; both p<0.001). Screening and treatment of chlamydia
      was associated with a significant decrease in the incidence of newborn febrile
      morbidity (10% versus 25%; p=0.02). In view of the high prevalence of positive
      results, it is cost-effective to offer universal screening in this setting.
      Failure to introduce a specific screening policy can result in a significant
      number of patients being denied the advantages of diagnosis and treatment.

PMID- 9761148
TI  - The incidence of abnormal findings from intrapartum cardiotocogram monitoring in
      term and preterm labours.
AB  - A retrospective analysis of 514 consecutive labours delivering 530 babies over a
      period of 18 months was conducted by a high-risk pregnancy team in a tertiary
      teaching unit to compare the incidence of abnormal findings from intrapartum
      monitoring between labours occurring before and at or after 34 weeks' gestation.
      Those delivered by elective Caesarean section, or Caesarean section at the onset
      of labour because of contraindications to labour and vaginal delivery, and those
      with congenitally malformed fetuses were excluded. Tracings were scored using the
      FIGO 1987 guidelines. Seventy-four labours and 83 babies delivered before 34
      weeks, and 440 labours and 447 babies delivered after 34 weeks in the study.
      There was a slightly higher incidence of suspicious CTG tracings (33.7% versus
      19.6%, OR 2.66, 95% CI 1.6-4.4) in the preterm group, due mainly to decreased
      baseline variability (p<0.001, OR 3.57, 95% CI 1.8-6.9), but the incidence of
      other pathological patterns did not differ. Using the same set of criteria for
      interpretation, there was a higher incidence of abnormalities from continuous
      cardiotocogram monitoring in the preterm group compared to term labours, but the
      intervention rate for fetal distress was not significantly increased. Appropriate
      interpretative criteria for intrapartum monitoring of preterm labours should be
      devised.

PMID- 9761149
TI  - Accuracy of automated blood pressure recorders in pregnancy.
AB  - Automated blood pressure recorders are used with increasing frequency by pregnant
      women, mostly without proper evaluation of their accuracy. We compared blood
      pressures (BP) recorded by 2 automated noninvasive devices, the Spacelabs 90207
      ambulatory blood pressure monitor and the OMRON HEM 705 CP portable self
      initiated device, with blood pressures recorded by routine sphygmomanometry in 79
      pregnant women either considered 'at risk' for preeclampsia or with mild
      hypertension in pregnancy. The Spacelabs device tended to overestimate systolic
      BP by a mean 11 (SD=8) mmHg and diastolic BP by 5 (SD=7) mmHg for phase 5
      pressure (p<0.001) but was similar to routine BPs for diastolic phase 4
      pressures. The OMRON device tended to underestimate diastolic (phase 4) pressure
      by 4 (SD=6) mmHg (p<0.001) but gave similar systolic and diastolic (phase 5)
      pressures to routine sphygmomanometry. However, for both devices there was
      considerable individual patient variability in accuracy. When using these devices
      to record a limited number of blood pressure recordings, as in this study, we
      suggest that individual comparison with mercury sphygmomanometry be made in each
      pregnant woman before accepting the validity of these recordings.

PMID- 9761150
TI  - Pregnancy and congenital heart disease--maternal and fetal outcome.
AB  - Two hundred and seventy five pregnancies in patients with congenital heart
      disease during 1980-1996 were analyzed retrospectively. Maternal and perinatal
      outcome was compared in 251 pregnancies of women with acyanotic and 24
      pregnancies of women with cyanotic heart disease. Congenital heart disease was
      diagnosed during the index pregnancy in 26.1% of patients and the majority
      (88.4%) were in NYHA classes 1 and 2. Atrial septal defect (27.7%) was the most
      common lesion in women with acyanotic heart disease and the majority with
      cyanotic heart disease had Eisenmenger syndrome, 13 of 21 (61.9%). Sixty
      pregnancies occurred in patients with surgically corrected lesions (acyanotic,
      56; cyanotic, 4). The incidences of abortions (8.3%), stillbirths (13.6%) and
      small for gestational age (SGA) (36.4%) were higher in cyanotic heart disease
      compared to acyanotic heart disease (stillbirth, 0.8%; SGA, 6.9%). There was a
      statistically significant difference in mean maternal age, mean gestational age
      and mean birth-weight in the surgically corrected and noncorrected lesions in
      both acyanotic and cyanotic heart disease. There was 1 maternal death in a woman
      with Eisenmenger syndrome.

PMID- 9761151
TI  - Intrapartum fetal oxygen saturation monitoring in congenital fetal heart block.
AB  - Conventional intrapartum electronic fetal heart rate monitoring is not
      informative in certain fetal conditions because the electronically-monitored
      fetal heart rate pattern is uninterpretable in terms of reflecting fetal
      normoxia. Such fetal conditions include various cardiac dysrrhythmias and some
      central nervous system abnormalities. Difficulties with intrapartum fetal welfare
      surveillance in such conditions often lead to operative delivery as a
      precautionary measure. We report 2 cases of intrapartum fetal oxygen saturation
      monitoring in the presence of congenital complete heart block (CCHB), using the
      Nellcor N400/FS14 oxygen saturation monitoring system. Mean intrapartum fetal
      oxygen saturation (FSpO2) was 32% (SEM +/- 1%) in the first case and 48% (SEM +/-
      0.3%) in the second case. In both cases, vaginal delivery of otherwise healthy
      infants was achieved. Fetal pulse oximetry is a promising new technique which
      directly measures fetal oxygenation without reference to fetal heart rate
      patterns. It may assist in the intrapartum fetal welfare assessment in conditions
      such as complete heart block, thereby helping to avoid otherwise unnecessary
      operative delivery.

PMID- 9761152
TI  - Induction of labour for post term pregnancy: an observational study.
AB  - The aim of the study was to compare the 2 management protocols for postterm
      pregnancy; elective induction of labour at 42 weeks' gestation and continuing the
      pregnancy with fetal monitoring while awaiting spontaneous labour. A
      retrospective observational study compared a cohort of 360 pregnancies where
      labour was induced with 486 controls. All pregnancies were postterm (>294 days)
      by an early ultrasound scan. Induction of labour was achieved with either
      prostaglandin vaginal pessaries or gel or forewater rupture and Syntocinon
      infusion. The control group consisted of women with postterm pregnancies who were
      not induced routinely and who usually had twice weekly fetal assessment with
      cardiotocography and/or ultrasound. Women who had their labour induced differed
      from those who awaited spontaneous labour. Nulliparas (OR 1.54; 95% CI 1.24-1.83)
      and married women (OR 1.76; 95% CI 1.45-2.06) were more likely to have their
      labour induced. There was no association between the type of caregiver and
      induction of labour. Induction of labour was associated with a reduction in the
      incidence of normal vaginal delivery (OR 0.63, 95% CI 0.43-0.92) and an increased
      incidence of operative vaginal delivery (OR 1.46; 95% CI 1.34-2.01). There was no
      difference in the overall rate of Caesarean section. There was no difference in
      fetal or neonatal outcomes. Parity had a major influence on delivery outcomes
      from a policy of induction of labour. Nulliparas in the induced group had worse
      outcomes with only 43% achieving a normal vaginal delivery (OR 0.78, 95% CI 0.65
      0.95). In contrast for multiparas, the induced group had better outcomes with
      less Caesarean sections (OR 0.88, 95% CI 0.81-0.96). This retrospective
      observational study of current clinical practice shows that induction of labour
      for postterm pregnancy appears to be favoured by nulliparous married women. It
      suggests that induction of labour may improve delivery outcomes for multigravas
      but has an adverse effect for nulliparas.

PMID- 9761153
TI  - Use of a focussed teen prenatal clinic at a military teaching hospital: model for
      improved outcomes of unmarried mothers.
AB  - We evaluated the utility of a focussed, multidisciplinary adolescent clinic in
      improving perinatal outcomes. The study population included all delivering
      unmarried teenagers (13-19 years) from January 1, 1993 to December 31, 1995
      attending the focussed adolescent obstetrical clinic compared to a similar cohort
      of married teenagers (13-19 years), married 20-24 year-old patients, and
      unmarried 20-24 year-old patients. There were no statistical differences in
      chorioamnionitis, intrauterine growth retardation (IUGR), postpartum haemorrhage,
      maternal weight gain, mean gestational age at delivery, preterm delivery rates
      (<37 weeks), low birth-weight (<2,500 g), Caesarean delivery, postterm delivery
      rates (>41 weeks), macrosomia (>4,000 g), placental abruption, chronic
      hypertension, alcohol use, Apgar scores or stillbirth rates or neonatal death
      rates among the 4 groups studied. Statistical differences were noted in mean
      delivery weights (p<0.05), preeclampsia (p<0.004), gestational diabetes (p<0.01),
      history of substance abuse (p<0.0001), tobacco use (p<0.0001), and forceps
      delivery rates (p<0.004). However, in the teen cohort none of these differences
      appeared to adversely affect perinatal outcomes in our patients. The focussed,
      adolescent obstetrical clinic appears to provide perinatal morbidities equal to a
      low-risk, general population generating better than expected outcomes for
      pregnant teenagers.

PMID- 9761154
TI  - Primipaternities in families: is the incidence of pregnancy-induced hypertensive
      disorders in multigravidas an anthropological marker of reproduction?
AB  - Pregnancy-induced hypertensive disorders (and especially preeclampsia) remain
      nowadays the major problem of human reproduction as it occurs in at least 10% of
      all world population births. It is a major cause of maternal-fetal mortality and
      morbidity in developed and developing countries. This disease was until recently
      classically considered as a disease of primigravidas with little recurrence in
      multigravidas. Nevertheless, recent evidences in the last half decade suggest
      that this disease is indeed a disease of first pregnancies, but at the level of a
      couple (primipaternity) rather than only the mother's side (primigravidity).
      Therefore, multigravidas share the risk with primigravidas in case of conception
      with a new partner. We expose the biological plausibility of this new approach
      (immunogenetic factors), and propose its epidemiological consequences with
      proposals of future research for health workers or demographers working at the
      level of populations. If pregnancy-induced disorders are disease of new couples,
      then their patterns are probably very different according to the broad
      reproductive patterns existing among different cultures (contraception,
      matrifocality or patrifocality, age at marriage, changes of reproductive partners
      et cetera).

PMID- 9761155
TI  - Maternal and umbilical cord serum zidovudine levels in human immunodeficiency
      virus infection.
AB  - The aim of this study was to determine the maternal and umbilical cord serum ZDV
      levels at delivery in HIV-1 infected parturients treated with a short-course ZDV
      regimens in late pregnancy and labour. Serum ZDV and its metabolite were measured
      by high-performance liquid chromatography. Concentrations of ZDV and its
      metabolite in umbilical cord blood appeared similar to maternal concentrations.
      There was a significant positive correlation between serum ZDV and its metabolite
      in maternal and umbilical cord concentrations. At delivery, maintenance of
      optimal virustatic ZDV concentration with oral antenatal and oral intermittent
      intrapartum ZDV dosage regimen can be achieved in only 53% of cases. The regimens
      used in this study were useful but not as effective as the ACTG 076 regimen with
      an intravenous dose intrapartum plus the oral administration to the infants for 6
      weeks.

PMID- 9761156
TI  - Timing and mechanism of perinatal human immunodeficiency virus-1 infection.
AB  - There is sufficient evidence indicating a higher vertical HIV-1 transmission rate
      in the last trimester and during labour compared with the first trimester.
      Antiretroviral therapy either single or in combination given to the mother during
      the last trimester and delivery can reduce the viral load in the maternal
      circulation. Vertical HIV-1 transmission during delivery can be minimized by
      appropriate timing and route of delivery. Elective Caesarean section before the
      onset of labour with an intact bag of forewaters provides the least mother-to
      fetus microtransfusion compared to other modes of delivery. Since an effective
      combination of HIV-1 immunoglobulin and HIV-1 vaccine given to the HIV-1 exposed
      newborns to prevent HIV-1 transmission similar to the viral hepatitis B model is
      not firmly established at present, postexposure antiretroviral prophylaxis and
      nonbreast-feeding are advocated for infants born from the HIV-1 infected mothers.
      In cases of advanced stage of maternal HIV-1 infection, and in developing areas
      where malnutrition prevails, an adequate supply of essential micronutrients is
      proposed as an adjunctive measure to reduce HIV-1 perinatal transmission.

PMID- 9761157
TI  - Preterm infants 30-36 weeks' gestation in Victoria--where should they be
      delivered?
AB  - There is little doubt that very preterm infants <30 weeks' gestation should be
      born in level-3 perinatal centres. For preterm infants 30-36 weeks' gestation,
      however, the optimum place of birth is not so clear-cut. The aims of this study
      of livebirths 30-36 weeks' gestational age born in Victoria were to determine: 1)
      the proportions delivered outside level-3 centres, and 2) for infants born
      outside level-3 centres, the proportions transferred after birth to a level-3
      nursery in the first days after birth. Data on the number of livebirths 30-36
      weeks' gestational age in Victoria in the 3 years 1994-1996, inclusive, were
      supplied by the Victorian Perinatal Data Collection Unit. Data were obtained from
      the Newborn Emergency Transport Service (NETS) on all transfers within the first
      3 days after birth to a level-3 centre for infants born outside level-3 centres.
      For the 3 years 1994-1996 there were 11,375 livebirths 30-36 weeks' gestational
      age in Victoria. The proportion born outside a level-3 perinatal unit was 57.9%
      overall, and rose with increasing gestational age, from 10.9% at 30 weeks to
      69.0% at 36 weeks. Of the 6,587 livebirths outside a level-3 centre, 808 (12.3%)
      were transferred within the first 3 days after birth by NETS to a level-3 centre,
      the proportions falling with increasing maturity, being 73.7%, 48.5%, 28.4%,
      26.9%, 18.8%, 11.8%, and 7.0% at 30, 31, 32, 33, 34, 35, and 36 weeks,
      respectively. These data may help medical practitioners when determining the
      place of delivery for infants 30-36 weeks' gestation.

PMID- 9761158
TI  - Mid-trimester ultrasound diagnosis of isolated talipes equinovarus: accuracy and
      outcome for infants.
AB  - Seventeen fetuses were diagnosed with isolated congenital talipes equinovarus
      (CTEV) on mid-trimester ultrasound at the Royal Women's Hospital, Melbourne,
      between January, 1992 and December 1995. Sixteen of the 17 cases had an
      amniocentesis performed and all karyotypes were normal. The remaining case was
      phenotypically normal, except for a clubfoot. None of the pregnancies was
      complicated by any of the recognized intrauterine environmental causes of CTEV.
      Four of the babies were delivered prematurely and all survived the neonatal
      period. Six (35%) infants did not have CTEV at birth, although 2 had postural
      varus feet. Nine of the 11 infants who did have CTEV at birth were treated within
      days of birth with plaster of Paris for periods of 6 to 12 weeks. Two infants
      required no further treatment, 5 required orthotics and 2 required surgery. The
      other 2 infants with CTEV at birth were treated with orthotics at 8 weeks of age.
      All infants were considered to have an excellent result at the 2 year follow-up.
      Seven (41%) of the prospective parents received antenatal counselling by an
      orthopaedic surgeon and the lack of study on outcome following an ultrasound
      diagnosis of CTEV was the impetus for our work.

PMID- 9761159
TI  - Assessing the teratogenic potential of angiotensin-converting enzyme inhibitors
      in pregnancy.
AB  - To assess the teratogenic potential of angiotensin-converting enzyme (ACE)
      inhibitors, we report on 20 prospective pregnancies and 85 identified from
      articles in the literature. The anomaly rate was 20.6% in small series <10
      entrants (95% CI 8.7-37.9%) and 1.4% in larger series > or =10 entrants (95% CI
      0.03-7.3%) p=0.0016. The most consistent anomaly seen, skull hypoplasia, along
      with renal dysfunction appear to be more related to prolonged or late pregnancy
      exposure than to first trimester exposure. There is little supportive evidence
      that ACE inhibitors (captopril or enalapril) are teratogenic. There seems to be
      no absolute reason to discontinue these 2 medications prior to pregnancy, nor to
      create anxiety when a patient is identified with the combination of early
      pregnancy and treatment with these medications. There appears to be reason to
      discontinue the medication in pregnancy but the adverse event rate cannot be
      assessed because of inadequate prospective information.

PMID- 9761160
TI  - Five successful deliveries following 9 consecutive spontaneous abortions in a
      patient with Wilson disease.

PMID- 9761161
TI  - Is it better to avoid urethral catheterization at hysterectomy and caesarean
      section?
AB  - This study involved 329 patients who had either a Caesarean section or a
      hysterectomy. A comparison has been made between 70 patients who were never
      catheterized and 251 who had a urethral catheter perioperatively. The absence of
      recognized urinary tract infections in those without a catheter was significant
      when compared with the 21 urinary infections identified in the catheterized group
      (p<0.05). The absence of urinary tract infections in the uncatheterized group
      clearly demonstrates the benefit of avoiding catheterization when possible.

PMID- 9761162
TI  - Nonfreeing of the lower leaf of the rectus sheath at caesarean section: a
      randomized controlled trial.

PMID- 9761163
TI  - Transvaginal sacrospinous colpopexy for posthysterectomy vault prolapse.
AB  - This study assesses the results of transvaginal sacrospinous colpopexy in the
      treatment of posthysterectomy vault prolapse; 114 of 135 women were available for
      follow-up between 8 months and 5 years after surgery. There was an initial
      overall satisfaction rate of approximately 90% and this was maintained at 80%
      even beyond 4 years. Those initially complaining of a lump or a swelling were
      relieved of the symptom in almost 90% of cases. Those with a drag or ache were
      cured in approximately 80% of cases. There was greatly improved bowel function in
      approximately 60% of patients and in approximately 60% there was cure of stress
      incontinence with additional buttressing sutures. Frequency and/or urgency was
      relieved in over 50% of the group and there was more comfortable intercourse in
      approximately 35% of those in whom this was a problem initially. As in previous
      series, subsequent prolapse is more likely to be in the anterior vaginal wall and
      there was an approximately 5% risk of this occurring over this period of follow
      up. The variation in technique in this series in which nonabsorbable Ethibond
      sutures were used to secure the vaginal vault to the sacrospinous ligament,
      appears to provide better long-term vault support than previous reports in the
      literature, without altering morbidity. Continuing follow-up will be required to
      confirm that this will prove to be so in the longer term. This series therefore
      confirms that the operation produces long-term support of the vaginal vault with
      preservation of a functional vagina, and has a satisfactory success rate in the
      relief of bladder and bowel symptoms associated with vault prolapse. However, it
      also demonstrates that in this mostly aged group of patients there will be a
      significant minority with limited relief of symptoms. It is important therefore
      that appropriate preoperative counselling is carried out so that patients have
      realistic expectations regarding the medium and long-term results of this
      procedure.

PMID- 9761164
TI  - Uterovaginal prolapse associated with rectal prolapse.
AB  - A case of combined genital prolapse and rectal prolapse in a 55-year-old
      multipara is reported. The mixed prolapse was treated by vaginal hysterectomy
      with pelvic floor repair and laparoscopic rectopexy at the same sitting. The
      feasibility of combined treatment of genital prolapse by the vaginal route and of
      rectal prolapse by laparoscopic rectopexy is emphasized.

PMID- 9761165
TI  - Uterus didelphys, a rare cause for tubal sterilization failure.
AB  - Uterus didelphys is a rare congenital anomaly. It can result in a variety of
      misadventures even in the hands of an expert. The present case reports uterus
      didelphys as the cause for tubal sterilization failure. This is the first case of
      this type seen in our institution in 35 years.

PMID- 9761166
TI  - Massive mature solid teratoma of the ovary with gliomatosis peritonei.
AB  - Glial implants on peritoneum and omentum may occur with mature solid teratoma of
      the ovary (gliomatosis peritonei). The case of a 17-year-old girl is presented,
      who had a massive solid ovarian teratoma with glial implants on visceral
      peritoneum and omentum. The massive size of the tumour posed difficulty in
      diagnosis. CT demonstrated a large teratoma. At laparotomy, the seedlings were
      initially thought to be evidence of malignancy and hysterectomy was offered which
      was refused by the parents. Oophorectomy was performed and the benign nature of
      the tumour and implants was seen on histopathology. It is important to recognize
      the benign nature of glial seedlings in such cases to avoid unnecessary extensive
      surgery.

PMID- 9761167
TI  - Ovarian dermoid cyst leakage--a cautionary tale.
AB  - This case illustrates that when a dermoid cyst is punctured, an immediate
      operative laparoscopy or laparotomy should be performed, along with lavage, to
      avoid the problems associated with dermoid cyst contents spillage.

PMID- 9761168
TI  - A casemix cost comparison of 2 treatments for ectopic pregnancy.
AB  - In this paper a retrospective cost comparison between laparoscopic treatment of
      ectopic pregnancy and conventional laparotomy under casemix funding has been
      performed. The total mean cost of laparoscopic treatment was $2,930 while the
      total mean cost of laparotomy was $4,259 per patient.

PMID- 9761169
TI  - The use of reproductive health services by young women in Australia.
AB  - Retrospective analysis of clinical data from 8 State/Territory Family Planning
      Organizations (FPO) was conducted to determine the reproductive health services
      used by young women. Between July, 1996 and June, 1997, a total of 185, 879
      client visits were recorded at FPO clinics, of which 72,303 (39%) were by young
      clients. The results showed that young women tended to use a combined oral pill,
      postcoital pill and spermicides more than those older than 25 years (p<0.05).
      Young women were also more likely to use services for management of sexually
      transmitted disease (STD), counselling for HIV, STD and sexual assault (p<0.05).
      However, there were considerable differences among the 3 groups of women:
      Aboriginal clients, those who did not speak English at home, and those who were
      born outside Australia. This study confirms that young women are using FPO
      services especially for emergency/postcoital contraception, STD screening and
      counselling. FPOs need to continue their existing role of providing reproductive
      and sexual health services catering to the need of this special segment of the
      population.

PMID- 9761170
TI  - Total parenteral nutrition (TPN) and steroid usage in the management of
      hyperemesis gravidarum.

PMID- 9761171
TI  - Cord entanglement in monochorionic diamniotic twins.

PMID- 9761172
TI  - Sacculation and retroversion of the gravid uterus in the third trimester.

PMID- 9761173
TI  - Primary genital non-Hodgkin lymphoma.
AB  - Although genital lymphoma either being an initial manifestation of occult nodal
      disease or secondary involvement is not uncommon, extranodal lymphoma originating
      primarily from the genitalia is quite rare. Here, we report a new case of primary
      genital lymphoma involving the uterus and ovaries, but not the Fallopian tubes.
      We also wish to emphasize that misdiagnosis of genital lymphoma, either
      clinically or histologically can occur.

PMID- 9761174
TI  - Re: The sign of stress incontinence--should we believe what we see?

PMID- 9761175
TI  - Re: Transvaginal sacrospinous colpopexy--a new and easier way.

PMID- 9761176
TI  - Use of the Shutt punch for transvaginal sacrospinous colpopexy.

PMID- 9761177
TI  - Re: Transvaginal sonography of the endometrium in south Indian postmenopausal
      women.

PMID- 9761178
TI  - Re: Bleeding associated with vaginal hysterectomy.

PMID- 9761179
TI  - Re: The debate regarding the risks of tocolytic agents.

PMID- 9761180
TI  - Re: Bleeding associated with vaginal hysterectomy.

PMID- 9761181
TI  - Molecular imprint polymers as highly selective stationary phases for open tubular
      liquid chromatography and capillary electrochromatography.
AB  - Chiral separations employing molecular imprint polymer (MIP) stationary phases in
      both open tubular liquid chromatography (OT-LC) and capillary
      electrochromatography (OT-CEC) are demonstrated. MIPs are highly crosslinked
      polymers containing spatial and functionality memory of template molecules which
      provide a higher degree of selectivity when used as stationary phases for
      chromatographic separations. Thin films of molecular imprinted polymers bonded to
      the inner walls of 25 microm ID fused-silica capillaries were prepared using an
      in situ polymerization technique developed in our laboratory that allows the use
      of conventional fused-silica capillaries with polyimide outer coatings. The
      success rate in preparing such open tubular columns was about 70%. Methacrylic
      acid and 2-vinyl pyridine were chosen as functional monomers, and either ethylene
      dimethacrylate or trimethylol propane trimethacrylate was used as the
      crosslinker. Toluene was employed as the porogen. Effects of polymerization
      conditions on column preparation and chromatographic performance were studied.
      Enantiomeric separations of D- and L-dansyl phenylalanines were achieved in both
      OT-LC and OT-CEC modes with good selectivity and efficiencies. Both types of
      separations may be performed on the same column using a single commercial
      instrument.

PMID- 9761182
TI  - Capillary electrochromatography of derivatized mono- and oligosaccharides.
AB  - An octadecyl-silica (ODS) stationary phase with light surface coverage of
      octadecyl ligands was introduced for capillary electrochromatography (CEC) at
      moderate electroosmotic flow (EOF) velocity. The ODS stationary phase was
      intentionally produced with light surface coverage in order to ensure a moderate
      EOF velocity across the packed capillary column, thus allowing relatively rapid
      analysis time. Despite the fact that the stationary phase leaves 75% of the
      surface silanols unreacted, fused-silica capillary columns packed with this ODS
      stationary phase exhibited reversed-phase behavior toward neutral alkylbenzene
      homologous solutes using hydroorganic eluents. Closely related p
      nitrophenylglycosides including some p-nitrophenyl-monosaccharides and p
      nitrophenyl-maltooligosaccharides were readily separated on the ODS capillary
      column within a relatively short analysis time. Also, alpha- and beta-anomers of
      some p-nitrophenyl-monosaccharides were readily separated in the presence of a
      small amount of borate buffer in the hydroorganic eluent.

PMID- 9761183
TI  - Capillary electrochromatography with novel stationary phases. I. Preparation and
      characterization of octadecylsulfonated silica.
AB  - A novel silica-based stationary phase was developed for use in capillary
      electrochromatography (CEC) at relatively high electroosmotic flow (EOF). The
      silica was first bonded with a relatively hydrophilic layer bearing strong
      sulfonic acid groups. To this charged polar sublayer, octadecyl functions were
      covalently attached to yield the nonpolar top layer. This novel stationary phase,
      referred to as octadecylsulfonated silica (ODSS), was packed in bare fused-silica
      capillaries or in capillaries with the same coating as the sublayer on the silica
      based stationary phase. The resulting packed columns were evaluated in CEC using
      alkylbenzenes as the test model solutes. Good separations can be achieved in less
      than 8 min, much faster than when using a regular octadecyl silica capillary
      column. Due to the permanent negative charge provided by the sulfonated sublayer
      on both the capillary walls and the silica particles, the magnitude of the EOF
      remained more or less constant over a wide range of pH, and its magnitude can be
      conveniently varied by the applied voltage.

PMID- 9761184
TI  - Method development in pharmaceutical analysis employing capillary
      electrochromatography.
AB  - Capillary electrochromatography (CEC) has been employed to explore method
      development for a series of structurally related polar neutral compounds of
      pharmaceutical relevance. Capillaries with dimensions of 75 microm ID x 25 cm
      length (34.5 cm total) were packed with Spherisorb ODS-1, Hypersil phenyl, and
      Hypersil MOS (all 3 microm particles) and were compared in the reversed-phase
      mode in order to determine which phase provided the best initial performance and
      thus serve as the phase of choice for additional method development experiments.
      The various separation parameters examined for their effect on efficiency, k',
      resolution, and linear velocity included percent and type of organic modifier,
      buffer concentration, voltage, and temperature. All separations were conducted
      with an acidic mobile phase (aqueous mobile phase component, pH 3.0). The
      separation efficiencies obtained were on the order of 200,000-260,000 plates/m,
      which equates to reduced plate heights of 1.22 for columns packed with Spherisorb
      ODS-1. Repeatable column-to-column separation performance was demonstrated.

PMID- 9761185
TI  - Micellar electrokinetic chromatography: a convenient alternative to colorimetric
      and high performance liquid chromatographic detection to monitor protease
      activity.
AB  - High performance capillary electrophoresis (HPCE) has been exploited as an
      analytical method alternative to current procedures for the determination of
      proteolytic activity of elastases from different sources. Due to some drawbacks
      with capillary zone electrophoresis (CZE), the mode of operation employed for the
      assay of elastolytic activity was micellar electrokinetic chromatography (MEKC).
      Using a background electrolyte consisting of 35 mM sodium tetraborate, pH 9.3,
      containing 65 mM SDS and 15% v/v methanol, separation of intact peptide substrate
      from products of proteolytic reaction was easily achieved in a fused-silica
      capillary of 50 cm effective length x 75 microm ID. This allowed us to determine
      the rate of hydrolysis of substrates and to calculate the kinetic parameters Km
      and k(cat) of the proteases investigated. A comparison of these data with those
      obtained from high performance liquid chromatography (HPLC)-based experiments
      showed that MEKC is a convenient technique for studying protease kinetics.

PMID- 9761186
TI  - Development of separation systems for polynuclear aromatic hydrocarbon
      environmental contaminants using micellar electrokinetic chromatography with
      molecular micelles and free zone electrophoresis.
AB  - Of four systems available from the literature, based on cyclodextrins,
      dioctylsulfosuccinate, bile salts, and molecular micelles consisting of oligomers
      of undecylenic acid, the most successful separation system in our hands is based
      on the molecular micelles, oligomers of sodium undecylenic acid (OSUA). We have
      employed organic additives of acetonitrile, acetone, and tetrahydrofuran in
      achieving separations of polyaromatic hydrocarbons (PNAs) using molecular
      micelles. Generally, successful separations are achieved with 20-40% composition
      as the organic additive in an 8 mM borate buffer. We separated 16 PNAs with 20%
      tetrahydrofuran in a system of 8 mM borate and 0.125 g/10 mL (ca. 6.25 mM) of
      OSUA. Typical extracts of environmental samples contain additional analytes
      besides the typical 16 target compounds. Among these are the nitrogen-containing
      aromatics that can act as cations under conditions of low pH and additional
      compounds that can act as anions under basic conditions in free-zone
      electrophoresis. These additional classes of analytes are separated by capillary
      zone electrophoresis/laser-induced fluorescence detection using a frequency
      doubled laser operated at 257 nm.

PMID- 9761187
TI  - Capillary electrophoresis chiral separations of basic compounds using cationic
      cyclodextrin.
AB  - Chiral separations of basic enantiomers were carried out by using a cationic
      cyclodextrin (CD), quaternary ammonium beta-cyclodextrin (QA-beta-CD), under
      counter-electroosmotic flow (counter-EOF) conditions. The special characteristics
      of using a cationic CD to separate cationic enantiomers is that the EOF can be
      reversed and the analyte-CD complexation is reduced. This is especially useful
      for chiral separation of cationic compounds, which strongly bind with neutral and
      anionic CDs (such as tricyclic amine compounds). The reduction in the binding
      constants between the CD and the cationic enantiomers makes it easier to control
      the optimum CD concentration. The application of the cationic CD also eliminated
      the peak tailing problem caused by electrodispersion. The effect of pH and the
      concentration of QA-betaCD on chiral separation has been studied. At pH 3.02, no
      separation for any of the enantiomeric amines was observed. At pH 8.20, chiral
      separation of some tricyclic compounds was achieved at very high resolution due
      to the counter-EOF setup. At pH 11.6, most enantiomers were neutral and chiral
      separation of some bicyclic compounds can be obtained.

PMID- 9761188
TI  - Capillary electrophoresis, nuclear magnetic resonance and mass spectrometry
      studies of opposite chiral recognition of chlorpheniramine enantiomers with
      various cyclodextrins.
AB  - Markedly different chiral separation abilities were observed for native beta
      cyclodextrin (beta-CD), carboxymethyl-beta-CD (CM-beta-CD) and heptakis (2,3,6
      tri-O-methyl)-beta-CD (TM-beta-CD) towards the enantiomers of (+/-)
      chlorpheniramine ((+/-)-CHL) in capillary electrophoresis (CE). Native beta-CD
      afforded almost baseline enantioseparation at a concentration of 18 mg/mL,
      whereas only 1 mg/mL solution of CM-beta-CD was required for adequate
      enantioseparation. TM-beta-CD allowed the nearly baseline enantioseparation only
      at a concentration as high as 80 mg/mL. Moreover, the migration order of (+/-)
      CHL in the presence of TM-beta-CD was opposite to that with beta-CD and CM-beta
      CD. 1H and 13C-NMR spectroscopy and electrospray ionization mass spectrometry
      (ESI-MS) have been used in order to obtain preliminary information about the
      stoichiometry and the binding constants in the intermolecular diastereomeric
      complexes of (+/-)-CHL with these CDs.

PMID- 9761189
TI  - Chiral separation of alpha-amino acids by ligand-exchange capillary
      electrophoresis using N-(2-hydroxy-octyl)-L-4-hydroxyproline as a selector.
AB  - The direct chiral resolution of underivatized alpha-amino acids by capillary zone
      electrophoresis (CZE) based on the principle of ligand exchange is described. An
      N-(2-hydroxyoctyl)-L-4-hydroxyproline/Cu(II) complex was used as a chiral
      selector. Besides amino acids containing aromatic residues, the basic amino acid
      histidine was resolved. Baseline separations were obtained for all amino acids
      investigated. The influence of selector concentration, electrolyte composition
      and pH on the resolution was investigated. It was found that there is a
      correlation between pI of the amino acids and the optimal pH.

PMID- 9761190
TI  - Chiral separation of polychlorinated biphenyls by micellar electrokinetic
      chromatography with sodium cholate.
AB  - Micellar electrokinetic chromatography (MEKC) with one kind of bile salt (sodium
      cholate) was used to separate three chiral polychlorinated biphenyls (PCBs; 84,
      95, and 176), each one in its two enantiomers. Sodium cholate was used as chiral
      surfactant in a 2-(N-cyclohexylamino) ethanesulfonic acid (CHES) buffer under
      alkaline (pH 10) conditions containing urea (2 M). The influence of bile salt
      concentration on the efficiency and the resolution between the two enantiomers of
      PCBs 84 and 95 was established. The chiral separation of three PCBs was
      successfully achieved in less than 30 min (approximately 23 min for PCB 176 and
      approximately 29 min for PCBs 84 and 95).

PMID- 9761191
TI  - Application of heparin to chiral separations of antihistamines by capillary
      electrophoresis.
AB  - A study of the chiral separations of antihistamines, including pheniramine,
      chlorpheniramine, brompheniramine, carbinoxamine and doxylamine in capillary
      electrophoresis (CE) was accomplished using heparin as a chiral additive (CA) and
      phosphate buffer as the background electrolyte. Several factors were shown to
      affect both the selectivity and the migration time, including concentration of
      heparin, concentration of buffer, and the pH. A dual mechanism involving both
      inclusion complexation and ionic interactions with heparin is thought to be
      responsible for the chiral recognition. In the pH range of 2.6-3.5 and reversed
      polarity, baseline resolutions were obtained using a wide range of buffer and
      heparin concentrations. Typically, chiral resolution was obtained within 50 min.

PMID- 9761192
TI  - Separation of neutral compounds by capillary electrokinetic chromatography using
      polyethyleneimine as replaceable cationic pseudostationary phase.
AB  - Polyethyleneimine (PEI, molecular weight 6 x 10(5) - 1 x 10(6)) is applied as a
      positively charged pseudostationary phase for electrokinetic chromatography (EKC)
      of uncharged mono- and oligophenols. EKC is carried out in PEI-coated fused
      silica capillaries (with electroosmotic flow directed towards the anode) in 2-(N
      morpholino)ethanesulfonic acid (MES) buffer (pH 7.0, 20 mM) with PEI added to the
      solution in concentrations up to 0.70% w/v. The pseudostationary phase leads to a
      retardation of the solutes mainly according to the number (and the position) of
      the OH-groups of the separands, and is not influenced significantly by methyl
      groups. For 0.70% w/v PEI solution, for instance, the relative retention, rho,
      has values between 0.33 and 0.53. For the systems with the highest resolution of
      the separands (0.25-0.30% PEI) 190,000 plates per meter are observed. The results
      indicate that the separation selectivity is mainly caused by ion-dipole
      interactions between the OH-groups of the solutes and the pseudostationary phase.

PMID- 9761193
TI  - Use of scavenger beads to remove excess labeling reagents from capillary zone
      electrophoresis samples.
AB  - In many cases, samples for capillary zone electrophoresis (CZE) are derivatized
      with a chromophore or fluorophore to enhance their detectability. To ensure
      efficient labeling, a large excess of labeling agent is often used, which leads
      to the presence of a large peak for unreacted reagent. Here we report that excess
      reagent can be reacted with "scavenger beads" carrying an appropriate functional
      group to remove it from the sample solution. We present examples of removal of
      aminonaphthalene mono-, di-, and trisulfonic acid from mixtures in which they
      were used to label mono- or oligosaccharides by reductive amination. Aldehyde
      containing scavenger beads were made by oxidizing Sephadex G-50 beads with sodium
      periodate. These were added to the labeling reaction mixtures after the reductive
      amination of the sugars was complete. Almost complete elimination of the peak
      from the labeling agent could be achieved.

PMID- 9761195
TI  - Capillary electrophoresis of arsenic compounds with indirect fluorescence
      detection.
AB  - A capillary electrophoresis (CE)-indirect fluorescence detection method for
      arsenic compounds is described. The five arsenic species, viz., arsenite
      (As(III)), arsenate (As(V)), monomethylarsonate (MMA), dimethylarsinate (DMA) and
      phenylarsonate (PhA), were efficiently separated by CE in 8 min with an 1.5 mM
      fluorescein solution at pH 9.8. Fluorescein also functioned as a background
      fluorophore for the indirect detection of these nonfluorescent arsenic species.
      Linearity (r> or =0.996) of more than two orders of magnitude was generally
      obtained. The relative standard deviation (RSD) values were in the ranges 0.4
      0.7% and 2.2-8.2% for migration times and peak areas, respectively. The
      concentration limits of detection (CLODs) for the arsenic compounds studied were
      between 0.04 and 0.16 microg/mL (as arsenic). The detection sensitivity was
      generally dependent upon the transfer ratio (TR, defined as the number of moles
      of fluorescein ions displaced by one mole of analyte ions) of each arsenic
      species. The applicability of the method for the analysis of ground water was
      examined.

PMID- 9761194
TI  - Capillary electrophoresis of anions at high salt concentrations.
AB  - It is commonly thought that even a moderately high ionic concentration in the
      background electrolyte (BGE) would lead to Joule heating and serious peak
      distortion. However, we obtained very satisfactory separations of both inorganic
      and organic anions in electrolyte solutions as high as 5 M sodium chloride using
      direct photometric detection. Samples containing a 0.5 M concentration of a salt
      can be analyzed directly by making the BGE concentration of the same salt even
      higher to obtain electrostacking. The temperature in the center of the capillary
      was calculated to be 49 degrees C when the current is at its maximum of 280
      microA. The effect of various salts on electrophoretic and electroosmotic
      mobility is discussed. Several examples are given of capillary electrophoresis
      under high-salt conditions.

PMID- 9761196
TI  - Characterization of micelles by capillary electrophoresis.
AB  - A practical approach for the characterization of pure micelles, and binary or
      ternary mixed micelles by capillary electrophoretic methods is presented.
      Interest is focused on the determination of mobility and composition of the
      micelles. The investigations are performed with bile salts, phosphatidylcholines
      and fatty acids. Pure bile salt micelles are characterized with the help of
      marking and displacement methods. Binary bile salt/phospholipid and ternary bile
      salt/phospholipid/fatty acid micelles are analyzed using capillary
      electrophoresis (CE) techniques with standard and improved UV detection, laser
      induced fluorescence and electrospray ionization-mass spectrometry (ESI-MS). For
      both the binary and the ternary systems, only one stable mixed micellar phase is
      found with a high negative mobility.

PMID- 9761197
TI  - The effect of blob size and network dynamics on the size-based separation of
      polystyrenesulfonates by capillary electrophoresis in the presence of entangled
      polymer solutions.
AB  - This work focuses on the separation of standard polystyrenesulfonates (PSS), with
      molecular masses (Mr) between 16 and 990 x 10(3) in capillaries filled with
      semidilute (entangled) linear hydrophilic polymers. Contrary to cross-linked
      chemical gels, which produce permanent networks, solutions of linear polymers
      lead to dynamic networks. The analytical performances and migration mechanisms
      are discussed on the basis of experiments performed in solutions of linear
      polyethyleneoxides and derivatized celluloses of various molecular masses. The
      influence of the mesh size and of the lifetime of the obstacles of the separating
      network has been investigated in detail. The mesh size is assimilated to the blob
      size of the separating polymer and is a decreasing function of its concentration.
      The lifetime of the obstacles of the network, identified with the reptation time
      of the polymer chain, characterizes its dynamics. This characteristic time
      increases with both the molecular weight of the separating polymer and its
      concentration. Its impact was first examined at fixed blob size. Then, the
      influence of the blob size was studied while keeping the reptation time of the
      network constant. By doing so, the existence of interactions between the solute
      and the separating polymer or between the solute and capillary wall can be more
      safely assessed. It appears that the reptation time of the mesh has a large
      influence on the electrophoretic mobility of the PSSs under a threshold value,
      which is of the order of magnitude of the time taken by the PSS to migrate on the
      blob size. Also shown are separations using networks made up with mixtures of
      polyethyleneoxides of the same nature and same mass concentration, but of very
      different molecular masses. This latter approach allows one to adapt the
      viscosity of the solution and the dynamics of the network, keeping the blob size
      constant.

PMID- 9761198
TI  - Analysis of antisense oligonucleotides by on-capillary isotachophoresis and
      capillary polymer sieving electrophoresis.
AB  - An attempt was made to evaluate the stability of an antisense oligonucleotide
      against nucleases present in HBL 100ras cells. To detect nanomolar concentrations
      of the oligonucleotide, a sensitive detection system was required. A combination
      of capillary electrophoresis/laser-induced fluorescence (CE-LIF) with
      fluorescence derivatization did not improve the sensitivity significantly and
      also resulted in loss of separation of the derivatized sample. On-column
      isotachophoresis for the preconcentration of oligonucleotide samples in DB-17
      coated capillaries filled with hydroxyethyl cellulose solution could be an
      alternative. The isotachophoresis (ITP) step allows injection of up to 40% of the
      capillary volume without loss in peak resolution and peak efficiency. Using ITP
      capillary polymer sieving electrophoresis (CPSE), the limit of quantitation at a
      signal-to-noise ratio of 10 was 73 ng/mL for a 12-mer oligonucleotide. Using
      these conditions, the gain in sensitivity was 125.

PMID- 9761199
TI  - Subnanomolar detection limit for sodium dodecyl sulfate-capillary gel
      electrophoresis using a fluorogenic, noncovalent dye.
AB  - Picomolar limits of detection are obtained using the noncovalent, fluorogenic
      dye, Sypro Red. The size separation of four commonly used sodium dodecyl sulfate
      capillary gel electrophoresis (SDS-CGE) molecular weight markers with 8% linear
      polyacrylamide (PAA) as the sieving matrix is used to construct a calibration
      curve for molecular weight determinations. SDS-CGE purity and molecular weight
      determination of purified chorismate mutase-prephenate dehydrogenase (CMPD) from
      Escherichia coli is shown to be comparable in accuracy with slab gel SDS
      polyacrylamide gel electrophoresis (SDS-PAGE). A migration time precision study
      indicates excellent reproducibility. Sypro red labeling of SDS-bovine serum
      albumin (SDS-BSA) complexes at nanomolar protein concentrations suggests assay
      detection limits surpassing those of silver staining. This detectability exceeds
      that achieved in previous SDS-CGE laser-induced fluorescence studies. This
      approach is expected to be easily adapted for use with commercial polymer
      formulations and automated instrumentation.

PMID- 9761200
TI  - Sodium dodecyl sulfate-capillary electrophoresis of proteins in a sieving matrix
      utilizing two-spectral channel laser-induced fluorescence detection.
AB  - We report a method for protein labeling, separation by capillary electrophoresis
      in a polymer sieving matrix, and detection by laser-induced fluorescence.
      Different dyes are used to label standard and sample proteins. A two-spectral
      channel detector resolves fluorescence from the sample and standards. Comparison
      of the migration time of the sample and standards permits the precise
      determination of molecular weight, irrespective of variations in run-to-run
      migration times.

PMID- 9761201
TI  - Nonaqueous capillary electrophoresis--its applicability in the analysis of food,
      pharmaceuticals and biological fluids.
AB  - The use of nonaqueous electrophoresis media for the application of capillary
      electrophoresis in the analysis of food, pharmaceuticals and biological fluids is
      reviewed. Some of the applications are discussed in detail and the benefits of
      using nonaqueous media in these cases are outlined. Three new applications within
      pharmaceutical analyses are presented. In these methods either a simple sample
      pretreatment by dilution with methanol (determination of chlorhexidine in a
      cream) or selective on-line capillary electrophoresis mass spectrometry (methods
      for identification of seizure drugs or opium alkaloids) are used. The choice of
      organic solvents and electrolytes for nonaqueous capillary electrophoresis are
      discussed. Furthermore, validation data obtained using capillary electrophoresis
      based on the nonaqueous principle are listed and discussed.

PMID- 9761202
TI  - Nonaqueous capillary zone electrophoresis for separation of free fatty acids with
      indirect fluorescence detection.
AB  - The feasibility of combining nonaqueous capillary zone electrophoresis with
      indirect fluorescence detection was studied for the efficient separation and
      sensitive detection of ionizable hydrophobic substances which do not possess
      practically suitable detection properties. Medium- and long-chain free fatty
      acids, C6-C24, were selected as test compounds. The results showed that such a
      wide range of medium- and long-chain free fatty acids could be separated between
      any two consecutive homologs in one run and be detected at a level of about 0.01
      0.02 mM in highly basic methanol/acetonitrile media containing fluorescein as
      coion of background electrolyte for indirect fluorescence detection.

PMID- 9761203
TI  - On-line capillary electrophoresis-electrospray ionization mass spectrometry using
      a polymerized anionic surfactant.
AB  - On-line capillary electrophoresis-electrospray ionization-mass spectrometry (CE
      ESI-MS) has been used to determine the tricyclic antidepressant drugs
      (imipramine, doxepin, and amitriptyline) as well as the beta-adrenergic blocker
      drugs (propranolol and alprenolol). A CE-ESI-MS interface linking a manually
      operated CE system and a Finnigan MAT-900 sector mass spectrometer (with an
      Analytica electrospray ionization source) has been constructed in-house and
      employed for this study. Although a water/methanol based capillary zone
      electrophoresis (CZE) buffer was initially used to determine these analytes,
      enhanced resolution was obtained by addition of a polymerized surfactant, i.e.,
      poly-sodium undecylenic sulfate (poly-SUS), into the electrokinetic
      chromatography (EKC) buffer. When a low concentration of this poly-SUS surfactant
      was added to a volatile EKC buffer, these structurally similar cationic drugs
      were EKC separated and on-line detected by ESI-MS.

PMID- 9761204
TI  - Pressure-assisted and pressure-programmed capillary electrophoresis/electrospray
      ionization time of flight-mass spectrometry for the analysis of peptide mixtures.
AB  - Pressure assisting and pressure programming the inlet of the capillary
      electrophoresis instrument were used for the analysis of peptide mixtures and
      protein digests using capillary electrophoresis/electrospray ionization-mass
      spectrometry (CE/ESI-MS). CE/ESI-MS of peptide mixtures and tryptic digests of
      proteins was studied using three different types of capillary columns: (i) a
      freshly aminopropylsilane (APS)-treated column, (ii) an untreated column, and
      (iii) a degraded APS-treated column. To maintain a constant and adequate buffer
      flow toward the CE capillary outlet for stable CE and ESI operation, low pressure
      was applied to the inlet of the CE when an untreated or degraded APS capillary
      was used. By programming the inlet pressure, CE/ESI-MS analysis time was reduced
      to 1/3 of its original time. The utility of this technique is demonstrated by
      CE/ESI-MS analysis of a hemoglobin variant (hemoglobin-S) and its tryptic
      digests. Identification of the mutant peptide in the tryptic digest of hemoglobin
      S was achieved by collision-induced dissociation (CID) of the protein digests
      using CE/ESI time of flight-mass spectrometry (TOF-MS).

PMID- 9761205
TI  - Enhanced sensitivity for sequence determination of major histocompatibility
      complex class I peptides by membrane preconcentration-capillary electrophoresis
      microspray-tandem mass spectrometry.
AB  - Sequence analysis of antigenic major histocompatibility complex (MHC) class I
      peptides requires minimizing sample loss and enhancing mass spectrometric
      sensitivity. In order to facilitate such analyses, we have coupled on-line
      membrane preconcentration-capillary electrophoresis (mPC-CE) with microspray mass
      spectrometry (mPC-CE-microMS) and tandem mass spectrometry (mPC-CE-microMS/MS).
      Specifically, cell lysate from approximately 10(9) EG-7 mouse tumor cells was
      immunoprecipitated and the released MHC class I peptides were subjected to
      reverse-phase HPLC. An HPLC fraction containing antigenic peptide(s) shown to
      induce T-cell stimulation was subjected to mPC-CE-microMS. Approximately 10
      microL (from 100 microL) of the fraction was pressure-injected and concentrated
      on a styrenedivinylbenzene (SDB) impregnated membrane. The peptides were eluted
      from the membrane with approximately 100 nL of 80% methanol, sandwiched between a
      leading stacking buffer (LSB, also serving as CE separation medium) of
      approximately 110 nL of 0.1% acetic acid in 10% methanol, and a trailing stacking
      buffer (TSB) of approximately 110 nL of 0.1% NH4OH. On application of the CE
      voltage the peptides are subjected to moving boundary transient isotachophoresis
      and focused. The peptides were separated in a Polybrene-coated capillary with
      application of -20 kV in reverse polarity mode and subsequently sprayed via an
      emitter coupled to the CE capillary by a liquid junction containing a platinum
      wire. An ion at m/z 482.3 was detected and subjected to mPC-CE-microMS/MS and
      determined to be SIINFEKL, a peptide (OVA) known to be antigenic in the mouse
      model system. Sensitivity enhancement over conventional mPC-CE-MS and MS/MS was
      approximately 100-fold.

PMID- 9761206
TI  - Capillary electrophoresis and capillary electrophoresis-electrospray-mass
      spectroscopy for the analysis of heterocyclic amines.
AB  - Fourteen heterocyclic amines (HAs) were analyzed by capillary electrophoresis
      (CE) on a polyvinyl alcohol (PVA)-coated capillary column. The optimized
      electrolyte is composed of 20 mM ammonium acetate, pH 3.0, and 20% methanol.
      Similar conditions were applied in electrospray-mass spectrometry (CE-ES-MS). The
      CE-ES-MS optimization procedure includes the position of the capillary in the
      stainless steel interface, the flow of the sheath liquid and its composition.

PMID- 9761207
TI  - Capillary electrophoresis interfaced to inductively coupled plasma mass
      spectrometry for element selective detection in arsenic speciation.
AB  - A method is presented to separate and detect six arsenic species by capillary
      electrophoresis (CE) interfaced to inductively coupled plasma mass spectrometry
      (ICP-MS). CE was used as a highly resolving separation system, whereas ICP-MS
      served as an element selective detector providing low detection limits. The
      special mode of operation included sample stacking and a differentiation of
      separation and detection. This provided separation and detection of six As
      species, uncharged and anionic, to be monitored within a single run. Detection
      limits were calculated according to IUPAC recommendation at 15 microg As/L for As
      (III), dimethyl arsinic acid (DA), monomethyl arsonic acid (MA) and As (V), or 65
      microg As/L for arsenobetaine (AsB) and arsenocholine (AsC). Investigations were
      focused on possibly occurring interferences, e.g., ArCl+ interference at the
      monoisotope 75As. Finally, real samples from biomedical field (urine) and
      environmental field (sewage sludge) were analyzed.

PMID- 9761208
TI  - Electrochemical detection in capillary electrophoresis with dual-parallel on
      capillary electrodes.
AB  - A new approach for dual electrode electrochemical detection in capillary
      electrophoresis (CEEC) is described. In this approach, two identical capillaries,
      each containing an on-capillary electrode incorporated permanently onto its tip,
      were paired together for simultaneous sample injection and detection. This
      procedure permitted dual-parallel detection to be performed without the need for
      painstaking alignment of the electrodes with respect to one another and to the
      capillary outlet as is required for the off-capillary microelectrode systems
      usually employed in CEEC. As a result, independent detection at two electrodes
      held at different potentials or at two electrodes of different composition or
      structure could be performed simply and with wide flexibility. Fabrication of on
      capillary electrodes was carried out by sputter-coating the exit end of the
      capillaries with a thin layer of Au or Pt. Dual electrode system performance was
      demonstrated by separation and analysis of phenol and catechol samples. In
      addition, the detection system was coupled with glucose oxidase for the selective
      detection of glucose.

PMID- 9761209
TI  - Fluorescence imaging of light absorption for axial-beam geometry in capillary
      electrophoresis.
AB  - A new method for investigation of axial-beam absorption detection for improved
      detection limits in microcolumn separations is reported. The method is based on
      fluorescence imaging of light absorption along a separation capillary. The
      probing UV light is introduced at one end of the capillary and shows an
      exponential fall-off along the capillary. As the UV light propagates through the
      sample peaks, an additional loss in intensity will be observed. In order to view
      the absorption profile along the capillary, a background fluorophore is added to
      the buffer. A charge-coupled device (CCD) detector and imaging optics are placed
      beside the capillary to view the capillary in a direction perpendicular to the
      capillary. Signal integration is employed for consecutive exposures as well as
      for neighboring detector pixels in order to increase the signal-to-noise ratio.
      Measurements for stilbene 3 with sulforhodamine B as a background fluorophore are
      presented. The characteristics of the detection method and potential improvements
      are discussed.

PMID- 9761210
TI  - A computer-controlled variable light attenuator for protection and autoranging of
      a laser-induced fluorescence detector for capillary zone electrophoresis.
AB  - Photodetectors have a limited range over which they can measure light intensities
      for any particular setting. The intensity of light reaching the detector can be
      kept within this range by using a liquid crystal variable light attenuator
      controlled by a computer that continuously checks the amount of light reaching
      the detector and adjusts the attenuation to an appropriate level. Using such a
      system we have constructed an intensified charge-coupled device (ICCD) camera
      based detector with a dynamic range of over six orders of magnitude which is
      never exposed to damaging or saturating light levels.

PMID- 9761211
TI  - Dual UV-absorbing background electrolytes for simultaneous separation and
      detection of small cations and anions by capillary zone electrophoresis.
AB  - The simultaneous separation and detection of small cations and anions by
      capillary zone electrophoresis (CZE) with indirect ultraviolet (UV) detection was
      successfully demonstrated in a background electrolyte (BGE) containing two UV
      absorbing components. Benzylamine, imidazole, benzenesulfonic acid,
      sulfosalicylic acid, and pyromellitic acid were tested as the components of the
      BGE. The success of the simultaneous separation of the cations and anions is
      dependent upon the proper selection of the electrolyte components and control of
      the migration of the ions towards the detector. High pH is beneficial to the
      detection of anionic analytes but not to the separation of cationic analytes
      because of large electroosmotic flow produced under this condition. The upper pH
      limit of the working pH range is confined by the pKa value of the cationic
      component of the BGE. The influence of pH and total electrolyte concentration on
      the electroosmatic flow (EOF) counteracted each other. This counteraction effect
      imposes an upper limit on the change of total electrolyte concentration at
      certain pH. It was found that the EOF should be larger by at least 10 x 10(-5)
      cm2V(-1)s(-1) than the electrophoretic mobilities of the anions so that the
      anions could be detected on the cathodic side within reasonable times and with
      good peak shapes. In the imidazole-sulfosalicylic acid BGE, the detection limits
      (signal to noise, S/N = 3) for the cations and anions ranged from 100 to 900 ppb.
      In the benzylamine-pyromellitic acid BGE, K+, Na+, Li+, CH3 COO-, HPO4(2-), F-,
      ClO3-, ClO4-, NO3-, NO2-, Cl- and SO4(2-) were separated within twelve minutes.
      The strategies for selection of the electrolyte components of the binary BGE were
      also discussed.

PMID- 9761212
TI  - Capillary electrophoresis/laser-induced fluorescence detection of fluorescein as
      a groundwater migration tracer.
AB  - Capillary electrophoresis (CE) has been applied to the determination of the
      groundwater migration tracer dye fluorescein based on laser-induced fluorescence
      (LIF) detection and compared to determinations obtained with traditional
      spectrofluorimetry. Detection limits of injected dye in the low parts per
      trillion (ppt) ranges have been accomplished with both CE/LIF based on the Ar ion
      laser and with a spectrofluorimeter. This approach was used for a real-world
      problem in determining groundwater migration between adjacent Resource
      Conservation and Recovery Act (RCRA) and Superfund sites by the Environmental
      Sciences Division in response to regional needs and as application of new
      analytical tools under development. Fluorescent dye was injected into source
      wells and then was determined in monitoring wells by extracting pads that
      adsorbed the dye or by directly determining the dye in the water using solid
      phase extraction (SPE), a preconcentration technique. The approaches based on
      CE/LIF exhibits increased specificity over existing approaches due to the
      separation and unique migration time of the dye. Additional studies were aimed at
      achieving sub-ppt levels in the water using solid-phase extraction and field
      amplified injection techniques.

PMID- 9761213
TI  - Factors influencing the choice of buffer in background electrolytes for indirect
      detection of fast anions by capillary electrophoresis.
AB  - The suitability of relatively slow (low absolute value of mobility) coanionic
      buffers in background electrolytes (BGEs) for indirect photometric detection of
      anions by capillary electrophoresis was investigated. As a model system, 2
      (cyclohexylamino)ethanesulfonic acid (CHES) was used to buffer the indirect
      detection electrolyte of sodium chromate. CHES (PKa 9.55) is a zwitterionic
      molecule carrying a net negative charge depending on the pH (effective charge 
      0.5 at pH = pKa). Within its useful pH buffering range CHES acted as a competing
      probe coanion. System peaks were induced which had deleterious effects on the
      detection sensitivity of slow to medium mobility anions. The mobility of the
      system peak was determined by the effective mobility of CHES, both of which
      increased with increasing pH. The peaks of analytes that migrated near or on the
      system peak were distorted and lost all quantitative properties. Analytes that
      migrated after the system peak either were not detected or reversed their
      responses. Analytes that migrated well before the system peak were unaffected.
      Consequently, the suitability of slow coanionic buffers is limited either to (i)
      fast anions or, (ii) a pH range much below the PKa, where the buffering capacity
      is not optimal.

PMID- 9761214
TI  - Capillary electrophoresis.

PMID- 9761215
TI  - Evidence from urinary cortisol that maternal behavior is related to stress in
      gorillas.
AB  - By studying western lowland gorillas (Gorilla gorilla gorilla, n = 8) in
      zoological gardens via ethological and non-invasive physiological techniques, we
      have demonstrated that their postpartum maternal behavior is related negatively
      to their postpartum urinary titers of cortisol. On the basis of this finding, it
      is proposed that postpartum stress contributes to disrupted maternal behavior in
      the gorilla in captivity. Morning urine samples were collected with a mean
      sampling interval of 1.6 days from Day 14 prepartum to Day 14 postpartum (n = 11
      pregnancies). Creatinine-indexed (Cr) urinary cortisol titers declined
      significantly between Day 9 to 1 prepartum (0.634 +/- 0.014 microg/mg of Cr, mean
      +/- SEM) and Day 1 to 6 postpartum (0.396 +/- 0.030 microg/mg of Cr, mean +/-
      SEM; p < 0.01-0.001). For each pregnancy, the relative postpartum decline in
      urinary cortisol was calculated as (microg of cortisol/mg of Cr Day 1 to
      4)/(microg of cortisol/mg of Cr Day -4 to -1). Values ranged from 0.35 to 1.12,
      were independent of absolute prepartum cortisol titers, and were interpreted as
      evidence of inter-female differences in postpartum hypothalamo-pituitary-adrenal
      axis activity and, therefore, postpartum stress. This postpartum stress index was
      negatively correlated with the amount of time (0-100%) that females carried and
      supported their 0-14 day-old infants in a ventral position during locomotion
      (r(s) = -0.68, p < 0.05) and tended to be negatively correlated with the total
      amount of time (0-100%) they spent in ventro-ventral contact with their infants
      (r(s) = -0.58; p < 0.10). This study provides the first physiological evidence
      that postpartum stress is an important etiologic factor in gorilla maternal
      failure in captive environments.

PMID- 9761216
TI  - Effect of prenatal stress on plasma corticosterone and catecholamines in response
      to footshock in rats.
AB  - The effect of prenatal stress was investigated on the sympathoadrenal response to
      novelty and footshock by measuring the time course of the changes in circulating
      corticosterone (COR) catecholamines and their metabolites. Pregnant rats were
      subjected to noise and light stress, three times weekly on an unpredictable basis
      throughout gestation. When the male offspring of stressed rats (PS) and those of
      unstressed mothers (C) were 4.5-5 months of age, they were prepared with
      indwelling catheters in the tail artery 24 h before the experiment. Resting
      levels of plasma COR, noradrenaline (NA), adrenaline (AD), dihydroxyphenylglycol
      (DHPG), dihydroxyphenylacetic acid (DOPAC), and dihydroxyphenylalanine (DOPA)
      were measured. Further blood samples were taken within 3 min of their transfer to
      the shock box, 1-2, 5, 15, and 45 min after footshock. Plasma COR was
      significantly higher in PS than in C rats at rest, but those of adrenaline, NA,
      and their metabolites did not differ in the two groups. Transfer of the rats to
      the shock box increased plasma COR, NA, adrenaline, and dihydroxyphenylglycol in
      both groups, and dihydroxyphenylalanine and dihydroxyphenylacetic acid only in PS
      rats. All the catechols increased further 2-3 min after footshock, except
      dihydroxyphenylalanine in PS rats. Plasma NA and dihydroxyphenylglycol levels
      were significantly higher in PS than in C rats immediately after footshock,
      indicating a greater activation of the sympathetic nervous system in PS rats. The
      findings demonstrate for the first time that prenatal stress can induce long term
      changes in the sensitivity of the sympathoadrenal system to stress.

PMID- 9761217
TI  - Effect of American ginseng (Panax quinquefolium) on male copulatory behavior in
      the rat.
AB  - The effects of American ginseng (Panax quinquefolium) on male rat copulatory
      behavior were investigated. Adult Sprague-Dawley rats were administered either
      10, 50 or 100 mg/kg of Panax quinquefolium or a sesame oil vehicle per os (p.o.)
      for 28 days and copulatory behavior parameters were measured. Ginseng-treated
      male rats demonstrated a significant decrease in mount, intromission and
      ejaculation latencies compared to vehicle controls. Hormone analyses revealed no
      difference in plasma luteinizing hormone or testosterone levels between ginseng-
      and vehicle-treated animals; however, plasma prolactin levels were significantly
      reduced by all doses of ginseng tested. When male rats were treated with the 100
      mg/kg dose of ginseng for 1, 14 or 28 days, mount and intromission latencies were
      significantly reduced at 14 and 28 days of daily ginseng treatment, whereas
      ejaculation latency was significantly reduced after 1 day of ginseng treatment
      when compared to vehicle controls. Plasma prolactin levels were also
      significantly decreased after 14 and 28 days of daily ginseng administration.
      There were no differences in body weight or in testes, seminal vesicle, anterior
      pituitary or spleen weights between ginseng- and vehicle-treated rats. These
      results demonstrate that P. quinquefolium significantly facilitates male
      copulatory behavior. The reduction in plasma prolactin levels suggests that
      ginseng-induced alterations in dopaminergic neurotransmission may play a role in
      the ability of P. quinquefolium to stimulate copulatory behavior in the male rat.

PMID- 9761218
TI  - Intestinal fat suppressed intake of fat longer than intestinal sucrose.
AB  - Although animals eventually stop eating when only experiencing the oro-sensory
      stimuli from a food, they stop eating much more rapidly if they also receive
      postgastric stimuli simultaneously. This suggests that the postgastric effects of
      a nutrient influence the hedonic value of food or motivation to consume that
      food, and thus, can influence food selection within the time frame of a meal. In
      this experiment, rats were equipped with a gastric fistula and duodenal cannula.
      This combination allowed them to receive the same oro-sensory stimuli, but
      different postgastric nutrients. While ingesting either a fat (Intralipid) or
      carbohydrate (sucrose) solution, both of which drained from the gastric fistula,
      the rats received a duodenal infusion of either sucrose (10 mLs, 0.24 kcals/mL),
      fat (10 mLs, 0.25 kcals/mL) or saline (10 mLs, 0 kcals/mL). While ingesting the
      Intralipid, a duodenal infusion of fat suppressed intake quicker and longer than
      an infusion of sucrose. While the animals ingested sucrose, sucrose and fat
      suppressed intake equivalently.

PMID- 9761219
TI  - Temporal dynamics of human masticatory sequences.
AB  - Many motor behaviors produced by humans and other mammals are temporally
      segmented. That is, sequences of rhythmic or repetitive behavior occur as a
      series of brief, 2- to 4-s bouts separated from each other by pauses or posture
      adjustments. Little is known about the physiological mechanisms underlying
      temporal segmentation, although several hypotheses have been advanced.
      Experimental and modeling studies are currently underway to gain insight into
      this phenomenon. One of the problems hampering advancement is the lack of
      relatively simple behavior models that can be studied in both humans and other
      mammals. We have recently reported that temporal segmentation occurs in guinea
      pig chewing sequences. Thus, it seems logical to explore whether temporal
      segmentation occurs in human chewing sequences as well. Toward this end, the
      current study evaluated the temporal dynamics of chewing sequences in humans.
      Thirteen subjects were videotaped on campus eating areas during lunch-time. Inter
      occlude intervals, i.e., time between maximum jaw closures, were calculated using
      a custom computer program, which also recorded whether the interval represented a
      chew or a pause in chewing. Chewing rate, pause durations, and chewing burst
      durations, i.e., duration of continuous chewing uninterrupted by pauses, were
      calculated. Median chewing burst duration for the sample was 2.91 s. This
      corroborates other studies' findings of 3-s temporal segmentation in repetitive
      movements. We conclude that automatic chewing sequences contain temporal
      segmentation. Future work is required to gain insight into whether the
      physiological mechanisms of this time-based phenomenon are similar among
      different species.

PMID- 9761221
TI  - Relationship of body energy status to inflammation-induced anorexia and weight
      loss.
AB  - The response to acute inflammation of rats at two levels of prior weight
      reduction were compared with normal-weight rats to examine how prior alterations
      in body energy status influence inflammation-induced anorexia and weight loss.
      Specifically, body weights were either reduced by 6%, the level of weight loss
      expected in normal-weight rats following induction of acute inflammation, or by
      12%, a level 6% below that expected of the normal-weight rats. Rats were either
      allowed to eat ad lib. on postinflammation Day 1 or were kept on food restriction
      until Day 5, when anorexia was no longer expected to be present. As predicted,
      normal-weight rats allowed to eat ad lib. beginning Day 1 displayed the most
      severe anorexia. Total food intake of this group over the first 5 days following
      inflammation induction was 33% less than the control (CON) group. Rats with 6%
      prior weight reduction displayed a milder anorexia, eating only 15% less than the
      CON group over the first 5 days. In contrast, rats with 12% prior weight
      reduction ate the same amount of food as the CON group. Interestingly, similar
      feeding patterns were observed in rats that resumed ad lib. feeding on Day 5. The
      outcome of these various feeding patterns was to bring body weights of all the
      inflammation groups to the same level, approximately 6% below CON group weights.
      These results provide further evidence that proinflammatory mediators induce a
      temporary reduction in the amount of body tissue (weight) spontaneously
      maintained that is directly proportionate to the magnitude of insult.

PMID- 9761220
TI  - Acute, early thermal experience alters weaning onset in rats.
AB  - We hypothesized that first ingestion of solid food (weaning onset) would be
      accelerated in young rats with advanced thermoregulatory development. To
      manipulate the pups' thermoregulatory development, we exposed rat pups, but not
      their dams, to a Cold (10 degrees C), Moderate (21 degrees C), or Warm (31
      degrees C) ambience for 2 h/day from postnatal Day 2-14, expecting that early
      exposure to cooler temperatures would accelerate development of thermoregulatory
      capabilities and thus accelerate nest egression as well as onset of feeding.
      Contrary to expectation, cold exposure was associated with a profile of
      developmental delays in both growth and maturation. Pups in the Cold condition
      began feeding later than pups with Moderate or Warm thermal experiences. We then
      evaluated thermoregulatory status (mechanisms for heat production and temperature
      conservation) on Day 15-16 (just prior to weaning onset). Thermogenesis, measured
      by oxygen consumption, was unaltered by the thermal manipulation. In contrast,
      pelage development (insulation) was altered. Pups in the Warm condition had
      greater fur density and an increased frequency of longer hairs relative to pups
      in the Cold condition. Although the developmental response to early cold exposure
      was in the direction opposite to our predictions, the hypothesized relation of
      thermoregulatory development to weaning onset was supported: Thermoregulatory
      status correlated with weaning onset.

PMID- 9761222
TI  - Increased flavor acceptance and preference conditioned by the postingestive
      actions of glucose.
AB  - In Experiment 1, rats were given daily 2-h access to chow and water and 20-h
      access to flavored solutions (cherry or grape). On alternate days, one flavor
      (CS+) was paired with intragastric infusions of 16% glucose and another flavor
      (CS-) with IG water. In subsequent choice tests, the rats strongly preferred
      (95%) the CS+ to the CS-. CS+ intake also greatly exceeded CS- intake during one
      bottle training sessions (71 vs. 18 g/20 h). This increased acceptance was due to
      both increased bout size and number. When CS+ was paired with IG water
      (extinction test), CS+ bout size declined to CS- levels, while CS+ bout number
      and total intake remained elevated. In Experiment 2, rats trained with sucrose
      octa acetate and citric acid solutions also showed increased CS+ acceptance and
      preference in one- and two-bottle tests, respectively. The rats also consumed
      more CS+ than CS- during short-term (30 min/day) one-bottle tests and intraoral
      intake tests under both deprived and ad lib. feeding conditions. These results
      demonstrate that the postingestive actions of glucose can condition substantial
      increases in flavor acceptance as well as flavor preference.

PMID- 9761223
TI  - Evidence that oral and nutrient reinforcers differentially condition appetitive
      and consummatory responses to flavors.
AB  - Rats tend to increase their intake of a flavor that has previously been paired
      with either sweet taste or with caloric repletion. However, it is unclear whether
      such a change in intake is caused by changes in appetitive behaviors such as
      orienting and approach, or changes in consummatory behaviors and oral
      responsiveness. Also, it is unclear whether oral reinforcers (sweetness) and
      postingestive reinforcers (nutrients) lead to the same kinds of behavioral
      change. In the current experiments, weanling rats with oral and gastric cannulas
      repeatedly experienced a flavor paired with either sweetness, high caloric
      density, or neither. Rats were then tested for differences in appetitive
      olfactory orienting and consummatory oral responsiveness elicited by the flavor.
      Results suggest that oral reinforcement (sweetness) produces conditioning of
      appetitive responding to the flavor, while postingestive reinforcement produces
      conditioning of consummatory responding. A second experiment indicates that these
      behavioral changes are specific increases in responsiveness conditioned by flavor
      + unconditioned stimulus (US) pairing, and are unlikely to be nonspecific effects
      of daily unconditioned stimulus exposure.

PMID- 9761224
TI  - Maltodextrin preloads reduce food intake without altering the appetiser effect.
AB  - The effects of consumption of a soup preload with added maltodextrin, relative to
      a no-maltodextrin control soup matched for sensory properties, on intake and the
      pattern of changes in rated hunger and fullness during lunch were investigated in
      24 male volunteers. Preloads were consumed 30 min before lunch and condition
      order counterbalanced. Intake at lunch was reduced significantly by 77 g (407 kJ)
      after the maltodextrin preload, and this reduced intake was associated with a
      significant reduction in eating rate but not meal duration. Hunger ratings were
      significantly lower, and fullness ratings significantly higher, at the start of
      lunch after the maltodextrin compared with control preload. However, the pattern
      of changes in subjective appetite once eating had started (assessed by analyzing
      best-fit quadratic functions between rated appetite and actual intake) did not
      differ between preloads. Neither the rated pleasantness of the lunch food at the
      start of the test meal nor the pattern of change in pleasantness across the meal
      differed between preloads. These results imply that the effect of maltodextrin
      preloads on appetite is to reduce the general desire to eat, and possible
      mechanisms for this effect are discussed.

PMID- 9761225
TI  - Sustained stress disrupts the performance and acquisition of delayed alternation
      in rats.
AB  - The effects of sustained stress on acquisition and performance of a delayed
      alternation task were studied in male rats. Rats lived 24 h per day in operant
      cages where they earned all of their food via lever pressing. During the stress
      portion of each experiment, one group of rats was able to avoid or escape
      signaled intermittent footshock (Avoidance/Escape group), a second group (Yoked)
      did not have control over shock termination, a third group never received shock
      (Control). Shock trials were presented around-the-clock at approximately 5-min
      intervals and the stress portion of each study lasted 1 week. We have previously
      reported that rats tolerate this paradigm well and avoid/escape 99% of the shock
      trials. Three experiments were conducted. In Experiment 1, rats learned the
      delayed alternation task prior to stress onset; in Experiment 2, rats were
      exposed to stress and the alternation task concurrently; in Experiment 3, rats
      were stressed for 14 days prior to being required to perform the delayed
      alternation task. In the first experiment, stress decreased both food intake and
      the accuracy of responding during the first days of stress. In the second
      experiment (acquisition), stressed rats required more days to reach asymptotic
      performance on the alternation task. In Experiment 3, rats stressed for 14 days
      prior to acquisition of the delayed alternation task performed similarly to
      controls.

PMID- 9761226
TI  - Age-related effects on reproductive function and sexual competition in the male
      prosimian primate, Microcebus murinus.
AB  - In the male lesser mouse lemur (Microcebus murinus), a polygamous long-day
      breeder of which the life span may reach 12-14 years, the effects of aging on
      socio-sexual relationships were studied on 44 captive animals of various ages. In
      this primate, new dominance relationships must be established at the beginning of
      each breeding season. During the breeding season induced by exposure to
      artificial long days, preoestrous females were introduced into cages of paired
      males to elicit sexual competition. Sexual behaviors, social interactions through
      chemical signals, and dominance relationships were recorded in paired males
      either of similar age (young or aged pairs), or of mixed ages. In all pairs,
      competition for priority access to females always occurred and dominance
      relationships were established unrelated to body weight. Although aged animals
      exhibited significantly less number of sexual and aggressive behaviors, they
      outranked younger males excepted when reaching oldest age. Independent of male's
      age, the typical pattern of seasonal rhythm of testosterone was observed, but
      aged males demonstrated a significant reduction in mean hormonal levels (25.5 +/-
      2.8 ng/mL, n = 8) compared to young animals (50 +/- 2.7 ng/mL, n = 8). Moreover,
      their hormonal response to photoperiod was phase-shifted leading to reduced
      testosterone values when females entered oestrus. Despite the fact that
      testosterone levels and sexual behaviors decreased with aging in this primate,
      older males reached a dominant position, increasing thus their reproductive
      success.

PMID- 9761227
TI  - Assessing olfactory performance in an Old World primate, Macaca nemestrina.
AB  - The present study demonstrates that an operant conditioning paradigm, originally
      designed for assessing olfactory performance in a small New World primate, the
      squirrel monkey, can successfully be adapted for use with a large Old World
      primate, the pigtail macaque. Using a task designed to simulate olfactory-guided
      foraging behavior, based on multiple discrimination of simultaneously presented
      odor stimuli, we could show that Macaca nemestrina is able to learn to
      discriminate between objects on the basis of odor cues. Moreover, they could
      readily transfer to new S+ and S- stimuli and could remember the significance of
      previously learned odor stimuli even after a 3-week break. Furthermore, we could
      show that this method is suitable for obtaining reliable measures of olfactory
      sensitivity. The few modifications of the original method employed here did not
      affect essential features such as the mode of stimulus presentation (odorized
      paper strips attached to manipulation objects) and the choice criterion (opening
      or rejecting the odorized manipulation objects), thus for the first time enabling
      valid interspecific comparisons of olfactory capabilities between a catarrhine
      and a platyrrhine primate species. Our results indicate that M. nemestrina and
      Saimiri sciureus are similar with regard to several measures of olfactory
      performance, such as speed of initial task acquisition and ability to master
      transfer tasks as well as their sensitivity to a food-related odorant.

PMID- 9761228
TI  - Analysis of steroid hormone levels in female mice at high population density.
AB  - Populations of predominantly female house mice (Mus musculus) were created by
      placing virgin female mice in cages (0.045 m2 to 0.48 m2) with a single stud
      male, and removing all ensuing male offspring at weaning. At maximum population
      size, the females in these all-female/one-male populations exhibited male-like
      aggressive behavior. Termination of the populations and subsequent measurement of
      steroid hormone levels indicated that the aggressive females had high circulating
      level of testosterone and corticosterone, and elevated baseline levels of
      progesterone. The high levels of corticosterone could be lowered by
      dexamethasone, but not the high levels of testosterone.

PMID- 9761229
TI  - Flavor preferences conditioned by intragastric sugar infusions in rats: maltose
      is more reinforcing than sucrose.
AB  - Prior research indicates that glucose conditions much stronger flavor preferences
      in rats than does fructose. This could occur because intestinal absorption of
      fructose is much slower than that of glucose and because fructose malabsorption
      may have aversive consequences. Fructose absorption is facilitated when glucose
      is also present in the gut. The present study therefore compared the flavor
      conditioning effects of maltose (a glucose + glucose disaccharide) to those of
      sucrose (a glucose + fructose disaccharide). In Experiment 1, rats had different
      flavors paired with intragastric infusions of 32% maltose (CS+M), 32% sucrose
      (CS+S), and water (CS-) 23 h/day. In subsequent two-bottle tests, both CS+
      solutions were strongly preferred to the CS-, but the CS+M was also preferred
      (78%) to the CS+S. Experiment 2A revealed that the rats also learned to prefer a
      CS+M to a CS+S when 16% sugar infusions were used. In Experiment 2B, the same
      rats preferred a flavor paired with 16% maltose to a flavor paired with 8%
      maltose. They did not reliably prefer a flavor paired with 16% sucrose to a
      flavor paired with 8% maltose. These results demonstrate that the postingestive
      actions of maltose are more reinforcing than those of sucrose. This indicates
      that fructose is less reinforcing than glucose even when malabsorption is not a
      factor. In contrast to their preference for the CS+M over the CS+S, the rats
      preferred sucrose to maltose when drinking the sugars by mouth. Therefore, sugar
      preferences mediated by oral taste receptors differ from those conditioned by
      postoral nutrient detectors.

PMID- 9761230
TI  - Vasopressin administration modulates anxiety-related behavior in rats.
AB  - Experiments were performed to measure the influence of centrally and peripherally
      applied arginine vasopressin (AVP) on anxiety-related behavior as indicated by
      the elevated plus maze test. Central administration was performed into the septum
      using a microdialysis technique. In initial experiments, the microdialysis probes
      were characterized for substance application in vivo by means of 125I AVP,
      measuring the substance-specific percent passover and the spatial distribution
      around the microdialysis membrane within the brain. Both microdialysis
      administration of 200 pg of AVP into the septum and and intraperitoneal
      application of 500 ng of AVP induced an increase in the percentage of time spent
      on the open arms of the elevated plus maze. The blockade of vasopressinergic
      neurotransmission or neuromodulation into the septal area by 40 ng of the AVP
      receptor antagonist d(CH2)5Thyr(Et)VAVP failed to induce a significant effect in
      this respect. The observation that neither centrally nor peripherally applied AVP
      influenced the locomotor activity on the elevated plus maze supports the
      hypothesis that AVP is involved in the modulation of anxiety-related behavior in
      rats.

PMID- 9761231
TI  - The olfactory loss that accompanies an HIV infection.
AB  - A number of studies have shown that HIV infection is associated with decreased
      olfactory ability. Additionally, it has been hypothesized that a reduced odorant
      identification may precede the advent of AIDS Dementia Complex (ADC). However, it
      is not known whether changes in olfactory ability are a manifestation of
      neurocognitive decline which may precede the appearance of AIDS Dementia Complex,
      damage to the peripheral olfactory system from opportunistic infection, or
      whether olfactory structures have a particular sensitivity to HIV. These issues
      were addressed in a cross-sectional study examining variability in the
      neuropsychological, neurological, otolaryngological, auditory, and olfactory
      status in HIV-positive subjects. A stepwise regression provided evidence that the
      ability to identify odorants was influenced by age, nasal structure and
      pathology, neurocognitive ability, and level of AIDS Dementia Complex. On the
      other hand, only nasal pathologies accounted for the variability in olfactory
      thresholds. These data suggest that identification and thresholds tests may
      reflect different olfactory pathologies. Additionally, these data suggest at
      least part of the decline in olfactory ability accompanying an HIV infection may
      be secondary to nasal pathologies. Because of their rapidly changing
      neurocognitive status, HIV-positive patients represent an excellent group in
      which to study the determinants of olfactory ability.

PMID- 9761232
TI  - Synergy between amylin and cholecystokinin for inhibition of food intake in mice.
AB  - Several gastrointestinal peptides which are secreted in response to nutrients
      have been reported to suppress food intake. Amylin is a peptide hormone co
      secreted with insulin from pancreatic beta-cells in response to nutrient stimuli.
      Cholesystokinin (CCK) is secreted from duodenal and jejunal mucosal cells in
      response to fat and protein. Amylin and CCK-8 have been reported to reduce food
      intake in rodents when given centrally as well as peripherally. Amylin injected
      intraperitoneally (i.p.) reduced food intake over the subsequent 30 min in
      overnight fasted mice by a maximum of 57 +/- 6% with an ED50 of 0.93 nmol/kg
      (3.63 microg/kg) +/- 0.34 log units. On a molar basis, this potency was similar
      to that of CCK-8 (ED50 0.85 nmol/kg (0.97 microg/kg) +/- 0.28 log units; p =
      0.93) which inhibited food intake by a maximum of 71 +/- 7%. When amylin and CCK
      8 were injected i.p. as an amylin:CCK-8 mixture, immediately before presentation
      of food in overnight fasted mice, food intake in the subsequent 30 min was
      reduced by a maximum of 91%, an amount that was greater than that producable by
      i.p. injection of amylin or CCK-8 alone. Isobolar analysis revealed a marked
      synergy between amylin and CCK-8 in reducing food intake, such that statistically
      ineffective doses of amylin and CCK, when combined, evoked near-maximal
      inhibition of food intake. Because the typical physiological event is for amylin
      and CCK both to be secreted in response to mixed meals, the synergy between them
      could indicate a shared role in physiological appetite control.

PMID- 9761233
TI  - Dietary protein restriction and selective preference for a protein-containing
      diet in the golden hamster (Mesocricetus auratus).
AB  - Two experiments were performed to examine protein appetite in golden hamsters
      (Mesocricetus auratus). In Experiment 1, hamsters were maintained for 10 days on
      either a protein-free or a nutritionally complete maintenance diet, and they were
      also given access to protein-rich and carbohydrate-rich test diets for 6 h/day.
      Hamsters maintained on the protein-free diet strongly preferred the protein test
      diet, but hamsters on the complete diet showed no such preference even when their
      caloric intake was matched to that of hamsters on the protein-free diet. In
      Experiment 2, hamsters that had developed a preference for the protein test diet
      while maintained on the protein-free diet were given Purina Chow for 25 days to
      permit them to recover from their protein deficiency. When later maintained on
      the complete diet, these hamsters did not demonstrate a preference for the
      protein test diet when maintained on the complete diet, but did so when returned
      to the protein-free maintenance diet. These findings indicate that dietary
      protein restriction causes hamsters to develop a strong preference for a protein
      rich diet and that this preference may be manifested only in response to a
      physiological need for protein.

PMID- 9761234
TI  - The relation between skin conductance level and plus-maze behavior in male mice.
AB  - The present study examined the correlation between anxiety scores and skin
      conductance level in 29 male Swiss Albino mice. Skin conductance (SC) was
      recorded with the SC unit and IBM-AT computer. Anxiety scores of mice were
      obtained from the elevated plus-maze test. The main result of the present study
      indicates that SC levels (SCLs) are negatively correlated with plus-maze behavior
      scores (both entries and time spent on the open arms). Our results are consistent
      with the findings which suggests that the higher the anxiety level the higher the
      SCL. This study further demonstrates the utility of SCL as a measurement for
      identifying anxiety in mouse. The interrelation between SCLs and plus-maze scores
      and possible explanations of the results are discussed.

PMID- 9761235
TI  - Sleep patterns of the volcano mouse (Neotomodon alstoni alstoni).
AB  - Sleep-waking patterns of the volcano mouse were studied under laboratory
      conditions. This rodent exhibits four states of vigilance: active wakefulness
      (Aw), quiet wakefulness (Qw), slow-wave sleep (SWS), and paradoxical (PS), or
      rapid-eye movement (REM) sleep. These states present, in general, the classic
      mammalian electrophysiological patterns. Although sleep periods were distributed
      at any time of the nychthemeral cycle, they showed the tendency to concentrate
      between 0800 and 2000 hours. The volcano mouse may be considered as a "good"
      sleeper, because it shows a relatively high percentage of sleep from the total
      recording time (TRT). Slow-wave sleep occupied 64.54 +/- 8.84% (mean +/- SD) of
      the total recording time, while 7.56 +/- 1.31% corresponded to rapid-eye movement
      sleep. The average duration of the rapid-eye movement sleep phase was 126.48 +/-
      17.79 s, exhibiting an average recurrence of 49 +/- 9.28 phases throughout the
      nychthemeral cycle. Mean duration of the sleep cycle was 9.23 +/- 2.36 min.
      Quantitative data of the volcano mouse sleep may be considered adequate for its
      body size and characteristic of an animal which sleeps in secure places under
      free-living conditions.

PMID- 9761236
TI  - AACC 50th anniversary retrospective. The evolution of immunoassay as seen through
      the journal Clinical Chemistry. American Association for Clinical Chemistry.

PMID- 9761237
TI  - Comprehensive analytical strategy for mutation screening in 21-hydroxylase
      deficiency.
AB  - Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease with a
      wide range of clinical manifestations. It is most often caused by deficiency of
      steroid 21-hydroxylase, reflecting any of a wide range of mutations in the 21
      hydroxylase (CYP21) gene. A major challenge in molecular diagnostics of CAH is
      the high homology between the CYP21 gene and the CYP21P pseudogene and the
      phenomenon of apparent gene conversion, which inactivates the functional gene. In
      this study we devised an improved stepwise diagnostic procedure involving
      nonradioactive Southern blotting and direct DNA sequencing. This strategy led to
      a successful elucidation of the molecular cause of the disease in 181 out of 182
      unrelated alleles in a total of 91 clinically and biochemically characterized
      patients. We were able to identify all classical known disease-causing mutations
      of the 21-hydroxylase gene and a novel nonsense mutation (bp 670, A-->C, Y97X).
      Our method also allows the reliable, secure diagnosis of the heterozygous
      configuration and may therefore be used for pre-, peri-, and postnatal diagnosis
      of CAH, even when informative data of the index patient are lacking. Furthermore,
      it can be used to confirm the diagnosis of CAH in newborns detected in 17
      hydroxyprogesterone screening programs.

PMID- 9761238
TI  - Plasma concentration, kinetic constants, and gene polymorphism of angiotensin I
      converting enzyme in centenarians.
AB  - We have determined serum activity and kinetic constants of angiotensin I
      converting enzyme (ACE), parallel to an insertion/deletion (I/D) polymorphism in
      its gene, in French centenarians and controls 20-70 years of age because this
      enzyme could have an impact on cardiovascular risk, and thus on longevity. Both
      the ACE D allele and ACE D/D genotype were more frequent in centenarians in
      comparison with controls, without sex-related differences nor significant
      correlation with a cardiovascular pathology. In centenarians, I/D polymorphism
      was correlated with circulating ACE activity (D/D genotype, 89.0 +/- 36.8 U/L;
      I/D genotype, 63.5 +/- 26.0 U/L; and I/I genotype, 55.1 +/- 39.4 U/L). The
      Michaelis constants for two substrates were identical whatever the genotype and
      were not different between centenarians and controls, i.e., 0.30 +/- 0.03 mmol/L
      for furylacryloyl-phenylalanyl-glycyl-glycine and 1.35 +/- 0.05 mmol/L for
      hippuryl-histidyl-leucine; for the latter, the optimal pH and activating
      concentration of chloride did not depend on I/D polymorphism. The maximal
      velocities with both substrates reflected the distribution of serum ACE activity
      as a function of the genotypes, in centenarians and in controls. In conclusion,
      plasma ACE activity is subject to a similar genotypic influence in centenarians
      as in adults 20-70 years of age; however, ACE itself appears to be functionally
      similar for each genotype. Furthermore, the D allele as well as the higher serum
      ACE activities associated with the D/D genotype cannot discriminate individuals
      at high risk for cardiovascular diseases, major causes of mortality before the
      age of 100 years.

PMID- 9761239
TI  - New sensitive method for the detection of the A3243G mutation of human
      mitochondrial deoxyribonucleic acid in diabetes mellitus patients by ligation
      mediated polymerase chain reaction.
AB  - An adenine-to-guanine mutation at nucleotide position (np) 3243 in the
      mitochondrial tRNALeu(UUR) gene is closely associated with various clinical
      phenotypes of diabetes mellitus. Because the mutation creates a new restriction
      site for the restriction enzyme ApaI, the mutation is usually detected and
      quantified by ApaI cleavage of the PCR products including np 3243. The
      sensitivity of the conventional method is, however, 5-10% heteroplasmy. The
      percentage of heteroplasmy of the mutation is usually highest in the affected
      tissues and is much lower in peripheral blood cells, which are used most
      frequently for the analysis. The sensitivity of the conventional method, however,
      is not sufficient to detect the mutation from peripheral blood cells. Utilizing
      ligation-mediated polymerase chain reaction, we have developed a feasible and
      sensitive method to detect 0.01% heteroplasmy of the 3243 mutation in peripheral
      leukocytes.

PMID- 9761240
TI  - Evaluation of the lysosome-associated membrane protein LAMP-2 as a marker for
      lysosomal storage disorders.
AB  - For many lysosomal storage disorders, presymptomatic detection, before the onset
      of irreversible pathology, will greatly improve the efficacy of current and
      proposed therapies. In the absence of a family history, presymptomatic detection
      can be achieved only by a comprehensive newborn screening program. Recently we
      reported that the lysosome-associated membrane protein LAMP-1 was increased in
      the plasma from approximately 70% of individuals with lysosomal storage
      disorders. Here we report on the evaluation of a second lysosome-associated
      membrane protein, LAMP-2, as a marker for this group of disorders. The median
      concentration of LAMP-2 in the plasma of healthy individuals was 1.21 mg/L,
      fourfold higher than the median LAMP-1 concentration (0.31 mg/L). LAMP-2 was
      increased in >66% of patients with lysosomal storage disorders, and the increases
      coincided with increased LAMP-1 concentrations. The reference intervals for LAMP
      1 and LAMP-2 in blood spots taken from newborns were 0.20-0.54 mg/L (n = 1600)
      and 0.95-3.06 mg/L (n = 1600), respectively. A high correlation was observed
      between the concentrations of LAMP-1 and LAMP-2 in both control and affected
      individuals. The higher concentrations of LAMP-2, relative to LAMP-1, in plasma
      make LAMP-2 an attractive marker; however, the final selection will be dependent
      on the availability of new diagnostic markers and their ability to detect
      disorders currently not identified by LAMP-2.

PMID- 9761241
TI  - K-ras mutations in stools and tissue samples from patients with malignant and
      nonmalignant pancreatic diseases.
AB  - Mutant-enriched PCR and reverse dot blot hybridization in microplates were
      applied for examining K-ras status in stools and tissue samples from patients
      with pancreatic tumors and chronic pancreatitis. In tissue samples, K-ras
      mutations were found in 32 of 35 cases of ductal adenocarcinoma, in 5 of 7
      periampullary cancers, in 1 cystadenocarcinoma, and in 3 of 5 patients with
      chronic pancreatitis. In stools, mutated K-ras was seen in 10 of 25 cases of
      ductal adenocarcinoma, in 1 case of cystadenocarcinoma, and in 2 of 6 cases of
      chronic pancreatitis. These data indicate that the K-ras status of stool samples
      may help identify pancreatic carcinoma and persons at risk for cancer
      development; however, it does not allow discrimination of malignant from
      nonmalignant diseases.

PMID- 9761242
TI  - Chemical mismatch cleavage combined with capillary electrophoresis: detection of
      mutations exon 8 of the cystathionine beta-synthase gene.
AB  - Mutation detection by chemical mismatch cleavage (CMC) is based on the chemical
      modification and cleavage at the site of mismatched C or T in heteroduplexes,
      using hydroxylamine or osmium tetroxide (OsO4) as chemical probes. In the present
      study, we evaluated CMC in combination with capillary electrophoresis (CE) by
      determining the common T833C and G919A mutations in exon 8 of the cystathionine
      beta-synthase gene in heterozygous and homozygous samples. A 186-bp fragment
      encompassing exon 8 was amplified by PCR with both primers labeled with 5'
      fluorescein. Labeled single strands of 40 and 61 nucleotides (nt) were formed
      from the coding strand of the T833C sample and non-coding strand from the G919A
      sample, respectively. These single-stranded DNA (ssDNA) products were analyzed
      under denaturing conditions by CE with short-chain linear polyacrylamide as the
      sieving matrix and were detected by laser-induced fluorescence (LIF), using a
      sensitive, one-channel sheath-flow detector. The CE-LIF format afforded
      relatively high resolution of ssDNA (down to 1 nt), precise size assessment of
      CMC products, sensitive detection with small sample requirements, and fast
      analysis. Thus, CMC combined with CE-LIF is suitable for screening of known
      mutations, giving expected CMC products, but will also detect unknown mutations,
      the locations of which are indicated by the fragment sizes.

PMID- 9761243
TI  - The precursor form of the human kallikrein 2, a kallikrein homologous to prostate
      specific antigen, is present in human sera and is increased in prostate cancer
      and benign prostatic hyperplasia.
AB  - Prostate-specific antigen (PSA, hK3) is a diagnostic marker for prostatic cancer
      but lacks the specificity to sufficiently distinguish between prostatic cancer
      and benign prostatic hyperplasia (BPH). Human glandular kallikrein 2 (hK2) has
      been proposed as a potential diagnostic marker for prostate cancer that could
      complement the current PSA test. Recently we demonstrated that proPSA is present
      in prostate cancer sera. This study examines the expression of prohK2 in prostate
      cells and its presence in human sera. Western blot analysis was used to assess
      prohK2 expression in the human carcinoma cell line, LNCaP. A highly specific and
      sensitive dual monoclonal immunoassay for prohK2 was developed and used to assess
      the presence of prohK2 in human sera. prohK2 was detected in the spent media of
      LNCaP cells. Furthermore, prohK2 was present at immunodetectable concentrations
      in human sera, and its concentration was increased in prostatic cancer and BPH.
      These results indicate for the first time that prohK2 is secreted by human
      prostate cells and is a major component of uncomplexed (free) hK2 in human sera.
      In addition, prohK2 in human sera is associated with prostate disease and thus
      may be a useful marker for prostatic cancer and BPH.

PMID- 9761244
TI  - Intra- and interindividual variability of carbohydrate-deficient transferrin,
      gamma-glutamyltransferase, and mean corpuscular volume in teetotalers.
AB  - Blood samples for determination of the biochemical alcohol markers carbohydrate
      deficient transferrin (CDT) in serum, gamma-glutamyltransferase (GGT) in serum,
      and erythrocyte mean corpuscular volume (MCV) were collected once every 1-2 weeks
      over approximately 5 months from 10 female and 4 male teetotalers. Mean values
      for serum CDT (using the CDTect assay) ranged from 9.9 to 29.4 units/L (median,
      14.2 units/L), and the highest results were obtained in the women. The mean
      values for serum GGT ranged from 0.15 to 0.49 microkat/L (median, 0.30
      microkat/L, or 18 U/L) except for one woman with a very high mean of 3.07
      microkat/L. For MCV, the mean values ranged from 79.5 to 91.5 fL. Two women
      showed several CDT results above the upper reference limit (mean values, 27.6 and
      29.4 units/L, respectively); however, their GGT and MCV values fell within the
      reference intervals. One of these women exhibited an increased total transferrin
      concentration (mean value, 5.38 g/L), which was possibly related to the use of
      oral contraceptives and/or a low serum iron concentration. When the CDTect value
      was expressed relative to total transferrin, a ratio within the reference
      interval was observed for this woman but not for the other woman with increased
      CDTect values. The present study demonstrates a considerable variation between
      individuals in CDT, GGT, and MCV without drinking any alcohol. The results also
      show that these baseline values are fairly constant over time within the same
      individual.

PMID- 9761245
TI  - Urinary free deoxypyridinoline by chemiluminescence immunoassay: analytical and
      clinical evaluation.
AB  - We evaluated an automated chemiluminescence immunoassay (CLIA) developed for the
      measurement of urinary free deoxypyridinoline (DPD). The new DPD method by CLIA
      is based on the competition of DPD with particle-bound pyridinoline for a limited
      amount of monoclonal mouse anti-DPD antibody. Total imprecision (CV) was 3.2-9.0%
      at 30-270 nmol/L. Regression analysis of urinary DPD concentration (second
      morning-void) measured by CLIA (y) and enzyme immunoassay (EIA) for adult
      volunteers (n = 449) with and without bone disease revealed a best fit equation
      of: y = 1.08 +/- 0.03x - 1.15 +/- 0.98 nmol/L (r = 0.964, S(y/x) = 14 nmol/L).
      CLIA and EIA methods were correlated with HPLC measurement of urinary free DPD (r
      = 0.846 and 0.871, respectively). For healthy adults, the creatinine-normalized
      excretion of DPD (mean +/- SD) measured by CLIA for 61 men (4.1 +/- 1.2 micromol
      DPD/mol creatinine) and 76 premenopausal women (5.3 +/- 1.8 micromol DPD/mol
      creatinine) did not differ significantly (P >0.05) from DPD excretion measured by
      EIA, and both immunoassays showed a significant gender difference (P <0.001) in
      reference intervals. In a clinical trial, DPD excretion (micromol DPD/mol
      creatinine) measured by CLIA differed substantially from the reference population
      for 54 untreated pagetic (12.7 +/- 8.0 SD), 255 untreated osteoporotic (7.5 +/-
      4.1), 21 osteomalacic (12.4 +/- 8.5), 17 primary hyperparathyroid (9.4 +/- 4.4),
      and 14 secondary hyperparathyroid (9.2 +/- 5.1) patients. Clinical sensitivities
      of the CLIA and EIA methods range from 38% to 80% in bone disorders and limit the
      use of the DPD measurement in disease detection. DPD excretion after pamidronate
      treatment in a subgroup of the pagetic patients fell dramatically as assessed by
      CLIA or EIA. We conclude that the automated CLIA method for DPD is a convenient
      and reliable method that may aid in the evaluation and management of bone disease
      and is applicable to high volume testing in the routine clinical laboratory.

PMID- 9761246
TI  - Rapid, quantitative nonisotopic assay for telomerase activity in human tumors.
AB  - Telomerase is a ribonucleoprotein enzyme that adds TTAGGG repeats onto human
      telomeres, preventing their shortening. The activation of this enzyme is an
      important step in cell immortalization and carcinogenesis and seems to represent
      a new and promising marker in cancer diagnosis and management. Telomerase
      activity is usually detected in cellular protein extract by the telomeric repeat
      amplification protocol (TRAP) assay, which can provide only a qualitative
      (presence/absence) evaluation. Here we present a modification of this method that
      can provide quantitative information without requiring time-consuming post-PCR
      procedures such as gel electrophoresis with radioactive materials and
      autoradiography. The detection and measurement of telomerase activity is
      performed by evaluating the amount of double-stranded DNA generated in the
      telomerase reaction and PCR amplification, with the use of the sensitive DNA
      fluorescent dye PicoGreen. In a subset of tumors, the presence of telomerase
      activity was confirmed by the conventional TRAP assay. By this method we
      evaluated telomerase activity in unselected groups of breast (n = 15), ovarian (n
      = 12), endometrial (n = 12), gastric (n = 20), and renal (n = 12) carcinomas, in
      meningiomas (n = 8), and in pheochromocitomas (n = 10). The results indicate
      substantial differences of telomerase activity among cancer groups; however, a
      large variability among patients of the same group is observed. Kidney, ovarian,
      and breast carcinomas showed the highest mean values (31.8 +/- 28.9, 29.2 +/-
      26.7, and 35.3 +/- 15.9 ng DNA/microg protein, respectively, mean +/- SD),
      whereas gastric and endometrial cancers had a lower activity (17.2 +/- 8.8 and
      13.5 +/- 7.9 ng DNA/microg protein, respectively). Very low or no detectable
      telomerase activity was found in meningiomas (with the exception of one malignant
      atypical variant) and pheochromocitomas (9.7 +/- 12.9 and 2.8 +/- 2.1 ng
      DNA/microg protein, respectively). In conclusion, our method seems to be an
      accurate and reasonable procedure for measuring telomerase activity in human
      cancers.

PMID- 9761247
TI  - Analytical and clinical performance characteristics of Tandem-MP Ostase, a new
      immunoassay for serum bone alkaline phosphatase.
AB  - The performance characteristics of the Tandem-MP Ostase assay, a new microplate
      immunoassay for bone-specific alkaline phosphatase (bone ALP; EC 3.1.3.1) in
      human sera, are described. Bone ALP is bound to streptavidin-coated microwells by
      a single biotinylated anti-bone ALP monoclonal antibody. Antigen is detected by
      the addition of p-nitrophenyl phosphate. The assay is performed at room
      temperature in <90 min. Imprecision was 2.3-6.1% with a detection limit of 0.6
      microg/L. Method comparison of bone ALP measurements with the Tandem-MP Ostase
      assay and the mass-based Tandem-R Ostase assay (n = 285) indicated regression
      statistics of Tandem-MP Ostase = 1.03 Tandem-R Ostase + 0.22 microg/L, S(y/x) =
      4.0 microg/L, r = 0.97. Serum bone ALP values in apparently healthy men and in
      pre- and postmenopausal women were also similar between the two Ostase assay
      formats. Liver ALP reactivity determined using the slope and heat inactivation
      methods was similar in both Ostase assays. Liver ALP reactivity ranged from 3
      microg/L (heat inactivation) to 6 microg/L (slope method) per 100 U/L of liver
      ALP activity, whereas bone ALP reactivity was 37 microg/L per 100 U/L of bone ALP
      activity, indicating a liver ALP relative reactivity of 8.1-16.2%. Similar
      results were obtained with the Alkphase-B bone ALP immunoassay. The Tandem-MP
      Ostase bone ALP assay demonstrated increased concentrations of serum bone ALP in
      conditions where bone metabolism is increased and showed a rapid, temporal
      decrease in serum bone ALP in Paget disease patients on bisphosphonate therapy.
      In conclusion, the Tandem-MP Ostase assay for serum bone ALP is a rapid, simple,
      robust nonisotopic alternative to the Tandem-R Ostase immunoradiometric assay
      that provides an accurate and sensitive assessment of bone turnover.

PMID- 9761248
TI  - Measurement of LDL particle size in whole plasma and serum by high performance
      gel-filtration chromatography using a fluorescent lipid probe.
AB  - We have recently described a technique for measuring LDL size by high performance
      gel-filtration chromatography (HPGC) with UV detection (Scheffer et al., Clin
      Chem 1997;43:1904-12). A drawback of this method is the necessity of LDL
      isolation before chromatography. We now describe a modification of this method
      based on selective detection of lipoproteins by postcolumn labeling with
      parinaric acid, a fluorescent lipid probe. Measuring the size of isolated LDL by
      HPGC in 56 subjects, we obtained diameters of 25.72 +/- 0.60 nm with UV detection
      and of 25.74 +/- 0.58 nm with fluorescence detection. The modified method is
      suitable for LDL size measurement in whole plasma or serum. LDL sizes measured in
      whole plasma correlated strongly with the respective values in isolated LDL (r =
      0.976) but were on average 0.18 nm larger (P < 0.001). CVs for within- and
      between-series imprecision were <0.25%. The present method requires only 5 microL
      plasma or serum without sample preparation and is suitable for the unattended
      analysis of large series of samples.

PMID- 9761249
TI  - Enzyme immunoassay of urinary mevalonic acid and its clinical application.
AB  - We have developed an enzyme immunoassay for mevalonic acid (MVA), using a
      specific monoclonal antibody. The intra- and interassay coefficients of variation
      calculated on two urine samples were 3.3% and 3.4%, respectively, in the
      intraassay precision test and 3.5% and 6.9% in the interassay evaluation.
      Pravastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase
      inhibitor, was administered to nine healthy men, and in all cases, their MVA
      excretion rates then decreased. The more MVA that was excreted in the urine
      before the pravastatin administration, the greater a reduction of MVA excretion
      was observed. The daily MVA excretions in healthy men (n = 120) and women (n =
      105) were 2.32 micromol/day (SD, 0.82 micromol/day) and 1.85 micromol/day (SD,
      0.47 micromol/day), respectively. In streptozotocin-induced diabetic rats (n =
      14), the plasma cholesterol concentrations and MVA excretion rates were
      increased, and a positive correlation was observed between the plasma cholesterol
      and the urinary MVA concentrations.

PMID- 9761250
TI  - Cyclosporin whole blood immunoassays (AxSYM, CEDIA, and Emit): a critical
      overview of performance characteristics and comparison with HPLC.
AB  - Assays with different specificity are used for cyclosporin monitoring in clinical
      transplantation. A recent survey of 35 centers showed that 86% used immunoassays
      for cyclosporin A (CsA). In consensus documents the following performance
      criteria were recommended: (a) imprecision < or = 10% at 50 microg/L and < or =
      5% at 300 microg/L; and (b) comparison with the reference method (HPLC) should
      yield a slope of 0.9-1.1, an intercept of -15 to 15 microg/L, and S(y/x) < or =
      15 microg/L. The newly developed CsA assays for the AxSYM (Abbott) and the CEDIA
      (Boehringer Mannheim) as well as the Emit assay (Behring Diagnostica) were
      evaluated. Results from samples of heart, kidney, and liver recipients (100
      specimens each) were compared with a validated HPLC-ultraviolet detection method.
      Between-series imprecision (CV) with commercial controls was 5.8% and 1.7% for
      AxSYM (70 and 300 microg/L), 11% and 5.5% for CEDIA (90 and 200 microg/L), and
      8.1% and 4.5% for Emit (63 and 172 microg/L). In the presence of 300 microg/L
      parent CsA, cross-reactivities were (for AxSYM, CEDIA, and Emit, respectively)
      7%, 4%, and none for AM1 (1 mg/L) and 12.6%, 25%, and 6% for AM9 (0.5 mg/L).
      Comparison with HPLC showed in heart and kidney recipients an average
      overestimation with the Emit and the CEDIA of approximately 22%, with
      overestimation in the AxSYM of 32%. In liver recipients, the most challenging
      patient group, the CEDIA and the AxSYM showed a mean overestimation of 43% and
      47%, respectively, and the Emit differed by 31% compared with HPLC. None of the
      immunoassays fully satisfied the performance criteria recommended in the
      consensus documents. In terms of specificity, Emit ranks before CEDIA, which
      ranks before AxSYM. Regarding imprecision, the ranking is AxSYM < Emit < CEDIA.
      These limitations must be considered when using these assays for therapeutic drug
      monitoring of CsA in clinical transplantation.

PMID- 9761251
TI  - Development of a sensitive ELISA for human leptin, using monoclonal antibodies.
AB  - A new, sensitive ELISA for human leptin in plasma and cerebrospinal fluid (CSF)
      was developed, using monoclonal antibodies. The lower limit of detection of this
      ELISA was 0.78 pg/assay. Both intra- and interassay imprecision values were <7%.
      The dilution curves of plasma and CSF showed good linearity, and the recovery was
      83.2-95.6%. There was good correlation between plasma leptin concentrations by
      the ELISA and a commercially available RIA (r = 0.99). Our ELISA is advantageous
      because it does not require radioisotopes, it produces results in hours rather
      than days, and more importantly, it improves on the detection limit and plasma
      interference of the RIA kit. The new ELISA enables measurement of low
      concentrations of leptin, as are seen in CSF and in plasma of patients with
      anorexia nervosa.

PMID- 9761252
TI  - Hemoglobin Rambam (beta69[E13]Gly-->Asp), a pitfall in the assessment of diabetic
      control: characterization by electrospray mass spectrometry and HPLC.
AB  - Hemoglobin (Hb) Rambam, or beta69[E13]Gly-->Asp, has been identified in a German
      woman also suffering from non-insulin-dependent diabetes mellitus and chronic
      obstructive pulmonary disease. This is the first observation of this Hb variant
      in a German family thus far. The detailed evaluation of its structure using
      electrospray mass spectrometry revealed new minor glycohemoglobin components and
      showed that the attachment of glucose to the beta NH2 terminus occurred at an
      almost identical rate in both wild-type and mutant beta-chains. However, the
      introduction of a carboxyl group at beta69 seems to increase the glycation of
      epsilon-amino groups of lysine residues. The glycemic state in the propositus was
      well reflected by the total glycohemoglobin concentrations but not by the Hb A1c
      values, which did not reflect hemoglobin glycation in this patient. This case
      demonstrates that Hb A1c cannot be used reliably in the management of diabetic
      patients carrying Hb variants such as Hb Rambam. Functional studies of the whole
      blood of the heterozygous carrier demonstrated extremely low oxygen affinity,
      which may have been caused by increased 2,3-diphosphoglycerate related to chronic
      obstructive pulmonary disease and hyperthyroidism. None of the clinical symptoms
      could be directly associated to Hb Rambam.

PMID- 9761253
TI  - The analog free testosterone assay: are the results in men clinically useful?
AB  - Men with low testosterone concentrations are usually hypogonadal. However,
      because variations in the testosterone transport protein, sex hormone-binding
      globulin (SHBG), directly influence the total testosterone concentration,
      confirmation of a low testosterone with a measurement of free testosterone or
      "bioavailable" testosterone (BAT) is recommended. In the present study, we
      examined the relationship of SHBG with free testosterone (Coat-A-Count assay,
      Diagnostic Products) and with BAT in men (n = 29) and women (n = 28) who
      participated in a study of the metabolic determinants of body composition. As
      expected, total testosterone was strongly positively correlated with SHBG among
      men (r = 0.68; P <0.01). Although the BAT was independent of SHBG in men (r =
      0.02), SHBG was an important predictor of free testosterone (r = 0.62; P <0.01).
      In contrast, in women serum concentrations of total testosterone (r = -0.26; P =
      0.17), free testosterone (r = -0.30; P = 0.17), and BAT (r = -0.46; P = 0.013)
      all tended to be lower with increasing SHBG. Free testosterone was nearly
      perfectly positively correlated with total testosterone (r = 0.97) in men, among
      whom free testosterone represented a relatively constant percentage of the total
      testosterone (0.5-0.65%), and the percentage of free testosterone was unrelated
      to SHBG. Thus the Coat-A-Count free testosterone concentration in men, like the
      total testosterone concentration, is determined in part by plasma SHBG.
      Accordingly, androgen deficiency may be misclassified with this assay in men with
      low SHBG. Moreover, the previous findings of reduced free testosterone
      concentrations with hypertension or hyperinsulinemia or as a risk factor for
      developing type 2 diabetes, conditions in which SHBG is reduced, may have been
      methodology-related.

PMID- 9761254
TI  - CO-oximetry interference by perflubron emulsion: comparison of hemolyzing and
      nonhemolyzing instruments.
AB  - Perflubron emulsion is expected to be in clinical use soon as a non-hemoglobin
      blood substitute. A preliminary report indicates that this new oxygen-carrying
      fluorocarbon interferes with the measurements of CO-oximeters. Therefore, we have
      quantified the interference that perflubron causes in the measurements of eight
      widely used oximeters and CO-oximeters. The AVL Omni 6, CC270, IL482, IL682, and
      OSM3 are conventional CO-oximeters that hemolyze blood samples before analyzing
      them. In contrast, the AVOXimeters 1000 and 4000 and the IL Synthesis 35 make
      their measurements without hemolyzing the samples. Because perflubron is expected
      to be used most frequently on surgical patients in a hemodiluted state, we
      conducted all tests on human erythrocytes suspended in plasma at a hemoglobin
      concentration standardized to 70 g/L (7 g/dL) and with oxyhemoglobin saturation
      set at 97%. When perflubron was added to the blood samples, the nonhemolyzing CO
      oximeters were not seriously affected by perflubron concentrations in and above
      the therapeutic range. In contrast, some of the hemolyzing CO-oximeters
      experienced concentration-dependent interference in their measurements of all
      analytes except total hemoglobin concentration. Thus, we conclude that the
      nonhemolyzing CO-oximeters provide an effective means for determining whether a
      hemolyzing CO-oximeter is experiencing clinically important interference in blood
      from patients receiving perflubron.

PMID- 9761255
TI  - Rapid pathogen detection using a microchip PCR array instrument.
AB  - An array of PCR microchips for rapid, parallel testing of samples for pathogenic
      microbes is described. The instrument, called the Advanced Nucleic Acid Analyzer
      (ANAA), utilizes 10 silicon reaction chambers with thin-film resistive heaters
      and solid-state optics. Features of the system include efficient heating and real
      time monitoring, low power requirements for battery operation, and no moving
      parts for reliability and ruggedness. We analyzed cultures of Erwinia herbicola
      vegetative cells, Bacillus subtilis spores, and MS2 virions, which simulated
      pathogenic microbes such as Yersinia pestis, Bacillus anthracis spores, and
      Venezuelan equine encephalitis, respectively. Detection of microbes was achieved
      in as little as 16 min with detection limits of 10(5)-10(7) organisms/L (10(2)
      10(4) organisms/mL).

PMID- 9761256
TI  - Reasons for a laboratory's inability to report results for requested analytical
      tests.

PMID- 9761257
TI  - Reference intervals for biochemistry parameters for evaluation of oxidative
      stress in human sperm.

PMID- 9761258
TI  - Evaluation and intermethod comparison of the Bio-Rad high-performance liquid
      chromatographic method for plasma total homocysteine.

PMID- 9761259
TI  - Use of real-time quantitative PCR to compare DNA isolation methods.

PMID- 9761260
TI  - Addition of sodium fluoride to whole blood does not stabilize plasma homocysteine
      but produces dilution effects on plasma constituents and hematocrit.

PMID- 9761261
TI  - Verification of multichannel liquid dispenser performance in the 4-30 microL
      range by using optical pathlength measurements in microplates.

PMID- 9761262
TI  - Oligo(dT)-immobilized pipette tip: efficient new methodology for mRNA preparation
      and direct gene amplification.

PMID- 9761263
TI  - Genotyping in urine: an interesting tool for epidemiological studies.

PMID- 9761264
TI  - False increase of cardiac troponin I with heterophilic antibodies.

PMID- 9761265
TI  - Reference intervals for four biochemistry analytes in plasma for evaluating
      oxidative stress and lipid peroxidation in human plasma.

PMID- 9761266
TI  - Limit of quantification (functional sensitivity) of the new IMx Tacrolimus II
      microparticle enzyme immunoassay.

PMID- 9761267
TI  - Temporal changes of serum antioxidant concentrations in a patient with diabetic
      ketoacidosis.

PMID- 9761268
TI  - False-positive CDTect values in patients with low ferritin values.

PMID- 9761269
TI  - Suitability of plastic collection tubes for cyclosporine measurements.

PMID- 9761270
TI  - Response to a report on false-positive results in a methadone enzyme immunoassay.

PMID- 9761271
TI  - Diagnostic criteria for diabetes mellitus.

PMID- 9761272
TI  - Effect of antiresorptive therapy on day-to-day variation of urinary free
      deoxypyridinoline excretion.

PMID- 9761273
TI  - Association between chronic hepatitis C virus infection and increased neopterin
      concentrations in blood donations.

PMID- 9761274
TI  - Diurnal variability and in vitro stability of carbohydrate-deficient transferrin.

PMID- 9761275
TI  - Desiccated coconut as a quality-control material in fecal fat measurements.

PMID- 9761276
TI  - Extracellular matrix production regulation by TGF-beta in corneal endothelial
      cells.
AB  - PURPOSE: Production of extracellular matrix (ECM) by corneal endothelial cells is
      related to physiologic functions and pathologic conditions and is regulated by
      many cytokines, including transforming growth factor-beta (TGF-beta). In this
      study, the molecular mechanism of ECM production regulation by TGF-beta was
      investigated in cultured corneal endothelial cells. METHODS: The production of
      ECM components (laminin and fibronectin) was detected in cultured corneal
      endothelial cells by western blot analysis. To determine the signal transduction
      pathways, mutant TGF-beta type I receptor (TbetaR-I) and/or Smad protein family
      members (intracellular signal transducers in TGF-beta signaling) were
      overexpressed by transfecting their cDNA into the cultured cells, and the effects
      on ECM production were observed. RESULTS: The production of laminin and
      fibronectin was stimulated by treatment with TGF-beta1 or TGF-beta2. After
      transient transfection of cDNA of the constitutively active (CA) mutant of TbetaR
      I, the production of laminin and fibronectin was stimulated even in the absence
      of TGF-beta. The transfection of the dominant negative mutant of TbetaR-I
      counteracted the effects of TGF-beta. These results confirm that TGF-beta
      directly stimulates ECM production from corneal endothelial cells through TbetaR
      I. The ECM production stimulation by TGF-beta or CA TbetaR-I was accelerated by
      the overexpression of Smad2, Smad3, and/or Smad4 and inhibited by that of Smad7.
      These results show that TGF-beta signals connected to ECM production are
      regulated by Smad family members, located downstream of TbetaR-I. CONCLUSIONS:
      The results of this study show that TGF-beta stimulates ECM production from
      corneal endothelial cells through TbetaR-I and Smad family transducers.

PMID- 9761277
TI  - Proteoglycan turnover in the sclera of normal and experimentally myopic chick
      eyes.
AB  - PURPOSE: The turnover of chick scleral proteoglycans from control and form-vision
      deprived (myopic) eyes was compared in vivo and in explant cultures to determine
      whether proteoglycan degradation is altered during the development of myopia and
      to characterize the mechanism of proteoglycan turnover in the sclera. METHODS:
      Seven-day-old chicks were radiolabeled via an intraperitoneal injection of 35SO4,
      and monocular form deprivation was induced 48 hours later. After 1, 2, and 3
      weeks of form deprivation, birds were killed, and the amount of 35SO4
      proteoglycans remaining in different scleral regions was measured in control and
      deprived eyes. Posterior sclera were also radiolabeled in organ culture
      containing 35SO4, and radiolabeled scleral proteoglycans were chased into
      unlabeled medium for 0 to 11 days. 35SO4-labeled proteoglycans within the scleral
      matrix and those released into the medium were characterized by Sepharose CL-2B
      chromatography and western blot analysis. RESULTS: The biological half-life of
      scleral proteoglycans was significantly shorter within the posterior pole of form
      deprived eyes (t1/2 = 7.212 days) compared with the same region of control eyes
      (t1/2 = 9.619 days; P < 0.001), whereas no differences in turnover rates were
      seen in the anterior sclera or equatorial sclera. When posterior scleral punches
      were placed in organ culture, 35SO4-labeled proteoglycan turnover rates were
      similar for control and form-deprived eyes. Chromatographic and western blot
      analyses indicated that approximately 80% of the total 35SO4 within the posterior
      sclera is incorporated into the aggrecan. Western blot analyses of aggrecan core
      protein released into the medium by control and form-deprived scleral punches
      indicated that the core protein was degraded into a series of smaller fragments
      of Mr = 102 to 220 kDa. A specific antiserum (anti-FVDIPEN) detected the presence
      of a 50-kDa C-terminal aggrecan fragment released into the medium, which was
      generated by the action of the matrix metalloproteinase gelatinase A and/or
      stromelysin. CONCLUSIONS: The turnover rate of 35SO4-labeled scleral
      proteoglycans is vision dependent and is accelerated in the posterior sclera of
      chick eyes during the development of experimental myopia. The loss of
      proteoglycans from the scleral matrix involves proteolytic cleavage at various
      sites along the aggrecan core protein through the action, at least in part, of
      gelatinase A and/or stromelysin.

PMID- 9761278
TI  - Raman detection of macular carotenoid pigments in intact human retina.
AB  - PURPOSE: To develop and test a novel noninvasive optical technique suitable for
      the objective measurement of macular carotenoid levels in human retina. METHODS:
      A resonance Raman scattering apparatus was constructed to measure carotenoid
      levels in flat-mounted human retinas and eyecups and in experimental animal eyes.
      Light from an argon laser was used to resonantly excite the electronic absorption
      of the carotenoid pigments, and scattered light was collected and analyzed by a
      Raman spectrometer. After carotenoid Raman measurements were completed on the
      retinal samples, macular carotenoid levels were determined by high-performance
      liquid chromatography (HPLC). RESULTS: Carotenoid resonance Raman scattering
      proved to be a highly sensitive and specific method for the noninvasive
      measurement of macular pigments in the human retina. Signal strength scaled
      linearly with actual macular carotenoid content as measured by HPLC. Our
      apparatus was also used to record resonance Raman signals from xanthophyll
      carotenoids stored in the retinal pigment epithelium of intact frog eyes.
      CONCLUSIONS: This new noninvasive optical method will facilitate studies of
      ocular carotenoid distributions and their role in degenerative diseases of the
      eye and may allow for the rapid screening of carotenoid levels in large
      populations at risk for vision loss from age-related macular degeneration, the
      leading cause of blindness in the elderly in the United States. A prototype
      clinical instrument is under development.

PMID- 9761279
TI  - Rabbit Streptococcus pneumoniae keratitis model and topical therapy.
AB  - PURPOSE: To develop a model for experimental Streptococcus pneumoniae keratitis
      and to evaluate the chemotherapeutic efficacy of 12 common topical antibiotics in
      vivo. METHODS: Five-hundred (CFUs of log-phase S. pneumoniae were injected into
      the central corneal stroma of 36 eyes of 18 rabbits. After 0, 4, 8, 16, 24, and
      48 hours, the in vivo growth was assayed as the CFU per cornea. Epithelial
      removal (to promote antibiotic entry and mimic human keratitis) was evaluated.
      Disc or tube dilution verification of the sensitivity or resistance of three S.
      pneumoniae strains was performed: a penicillin sensitive ("S"), an intermediate
      sensitive ("I"), and a resistant ("R") strain. Keratitis was established with S.
      pneumoniae "S" in 65 eyes, S. pneumoniae "I" in 107 eyes, and S. pneumoniae "R"
      in 78 eyes. Sixteen hours later, control corneas were harvested and the
      epithelium removed from treatment corneas. Every half hour saline, penicillin,
      gentamicin, bacitracin, ciprofloxacin, ofloxacin, erythromycin, vancomycin,
      ceftriaxone, cefotaxime, or chloramphenicol was applied for 5 hours. One hour
      later CFUs/cornea were assayed. RESULTS: After 24 hours, S. pneumoniae "S" and
      "I" had proliferated to 9.18+/-6.65 x 10(6) CFUs and 9.26+/-6.90 x 10(6) CFUs.
      Epithelial removal at 16 hours was not significant. The in vitro antibiotic
      sensitivity was as expected. However, in vivo, penicillin, gentamicin, or
      cefazolin sterilized S. pneumoniae "S." S. pneumoniae "R" responded best to
      fortified gentamicin with or without vancomycin; all others antibiotics were
      significantly less effective (P < 0.001). CONCLUSIONS: A small intracorneal S.
      pneumoniae inoculum in rabbit corneas grew and was maintained for 24 hours (with
      epithelial removal) to provide a model for testing antibiotic sensitivity in
      vivo. Topical penicillin is best for treating keratitis from penicillin-sensitive
      S. pneumoniae, whereas topical gentamicin or a combination of gentamicin and
      vancomycin was most effective against penicillin-resistant S. pneumoniae.

PMID- 9761280
TI  - Myofibroblast transformation of cat corneal endothelium by transforming growth
      factor-beta1, -beta2, and -beta3.
AB  - PURPOSE: Under certain pathophysiologic conditions, the corneal endothelium can
      produce an abnormal posterior collagenous layer (PCL) that reduces light
      transmission. Previous studies suggest that formation of PCLs can result from
      transformation of endothelial cells to a proliferative myofibroblast phenotype.
      The purpose of this study was to determine the potential role of transforming
      growth factor (TGF)-beta on corneal endothelial transformation. METHODS: Three
      corneal buttons (6-mm diameter) were obtained from each cornea of 28 adult cats.
      After a 2-mm diameter mechanical scrape injury was made, each button was cultured
      for 24, 48, or 72 hours in serum-free medium (SFM) or SFM supplemented with 10%
      fetal calf serum, TGF-gamma1, TGF-beta2, TGF-beta3, basic fibroblast growth
      factor (bFGF), or TGF-beta1 and bFGF. Buttons were single and double labeled
      using phalloidin and antibodies to ZO-1, Ki67, fibronectin, alpha-smooth muscle
      (SM) actin, and vinculin. Counts of Ki67-positive cells were used as a measure of
      endothelial proliferation. RESULTS: Organ culture in TGF-beta1, beta2, or beta3
      induced myofibroblast transformation of corneal endothelial cells, with formation
      of stress fibers containing alpha-SM actin, loss of normal pericellular ZO-1
      organization, development of extracellular fibronectin fibrils, and formation of
      focal contacts as indicated by punctate vinculin staining. However, TGF-beta3 did
      not stimulate endothelial proliferation above that in serum-free control samples.
      Serum and bFGF each stimulated proliferation significantly, without inducing
      myofibroblast transformation. A combination of TGF-beta1 and bFGF resulted in
      both myofibroblast transformation and increased proliferation. CONCLUSIONS: These
      results suggest that TGF-beta plays a key role in the loss of normal endothelial
      differentiation, abnormal extracellular matrix synthesis, and myofibroblast
      transformation, which can induce development of PCLs. However, other factors such
      as bFGF seem to be required to stimulate concomitant proliferation of corneal
      endothelium.

PMID- 9761281
TI  - Investigation of multifocal visual evoked potential in anisometropic and
      esotropic amblyopes.
AB  - PURPOSE: To investigate the variation of visual evoked potential (VEP) function
      at different eccentricities of the visual field in esotropic amblyopes and
      anisometropic amblyopes. METHODS: Data from 5 esotropic amblyopic eyes, 6
      anisometropic amblyopic eyes, and 45 control eyes were analyzed. A VERIS system
      was used to generate a stimulus matrix containing 61 hexagons on a computer
      monitor. Each hexagon of the display contained a number of small black and white
      hexagonal patches that reversed in polarity during stimulation according to a
      pseudorandom binary m-sequence. The VERIS system extracted the local responses by
      cross-correlating the input and output signals. The latencies and amplitudes of
      the responses from the central 8.6 degrees of arc in the visual field were
      analyzed. RESULTS: In esotropic amblyopia, the multifocal VEP latency is
      prolonged, and the amplitude is reduced in the central region of the visual
      field. The mean amplitude is significantly smaller, and the mean latency is
      significantly longer in the temporal visual field than in the nasal visual field.
      In anisometropic amblyopia, latencies are markedly prolonged, and the amplitudes
      of multifocal VEP are attenuated in the central region of the visual field, and
      these effects are lessened in the periphery. CONCLUSIONS: The results are in
      agreement with psychophysical studies reporting a greater foveal deficit in
      amblyopia and a greater visual loss in the temporal field than in the nasal field
      in esotropic amblyopia.

PMID- 9761282
TI  - Two pore types in the inner-wall endothelium of Schlemm's canal.
AB  - PURPOSE: It has been reported that fixation conditions significantly influence
      the apparent pore density in the inner-wall endothelium of Schlemm's canal. In
      the present study, the manner in which fixation conditions affect the two
      subtypes of inner-wall pores, intracellular pores and intercellular (or border)
      pores, was investigated. METHODS: Outflow facility was measured in enucleated
      human eyes. Eyes were fixed under constant flow" or constant pressure conditions,
      microdissected to expose the inner wall of Schlemm's canal, and prepared for
      scanning electron microscopy. The density and diameter of the two subtypes of
      pores in the inner wall were measured. RESULTS: Intracellular pore density
      decreased with increasing postmortem time (P < 0.001) and increased with
      increasing volume of fixative passed through the outflow pathway (P < 0.001),
      whereas border pore density showed no dependence on these parameters (P > 0.25
      and P > 0.15, respectively). Border pore density increased with increasing
      fixation pressure (P < 0.005), even though intracellular pore density showed no
      such dependence (P > 0.4). No correlation was found between outflow facility and
      the predictions of Poiseuille's law, Sampson's law, or the funneling theory for
      the hydraulic conductivity of the intracellular pores (P > 0.35) or the border
      pores (P > 0.1). CONCLUSIONS: The intracellular and border pores form two
      morphologically and functionally distinct populations in the inner wall of
      Schlemm's canal. The dependence of intracellular pore density on postmortem time
      and on volume of fixative passed through the outflow pathway suggests that these
      pores are artifacts of tissue fixation or processing conditions. That border
      pores do not depend on such conditions and that their presence is correlative
      with perfusion pressure suggests that this population may be nonartifactual. New
      histologic techniques for examining the inner wall of Schlemm's canal are
      necessary to determine the in vivo state of inner-wall pores and how they
      influence outflow facility.

PMID- 9761283
TI  - Immunotolerance against a foreign antigen transgenically expressed in the lens.
AB  - PURPOSE: To extend our knowledge concerning immunotolerance against autologous
      lens crystallins, transgenic (Tg) mice that express a foreign antigen in their
      lens were generated, and the immune response against the antigen in these mice
      was analyzed. METHODS: Conventional techniques were used to generate lines of Tg
      mice that express soluble (S-) or membrane-bound (M-) hen egg lysozyme (HEL)
      under the control of the alphaA-crystallin promoter. The presence of HEL in
      various organs was determined by the particle concentration fluorescence
      immunoassay (PCFIA), and reverse transcription-polymerase chain reaction
      technique was used to detect mRNA transcripts of the molecule. To examine the
      development of immunity (or tolerance), Tg mice and their wild-type controls were
      immunized with HEL (25 microg) in Freund's complete adjuvant and 14 days later
      were tested for immune response against the antigen. Cellular immunity was
      measured by the lymphocyte proliferation assay and cytokine production, and
      humoral immunity was determined by enzyme-linked immunosorbent assay. RESULTS:
      Eyes of the high copy number M-HEL Tg mice were dystrophic, with disrupted lens,
      whereas no morphologic changes were detected in the eyes of the other Tg mouse
      lines. All Tg mice exhibited tolerance to HEL by their cellular and humoral
      immune compartments. The state of immunotolerance to HEL was retained in the Tg
      mice for as long as 10 months after removal of the main depot of this protein, by
      enucleation. Measurable amounts of HEL were found in the eyes of all Tg mice, but
      the protein could not be detected in the serum or in other organs by the
      sensitive PCFIA (with a threshold of 1 ng/ml). Yet, HEL mRNA was found in the
      thymus of the Tg mice, suggesting that minute amounts of the protein are
      expressed in this organ. CONCLUSIONS: The unresponsiveness to HEL in the Tg mice
      seems to be due to a "central" mechanism of tolerance, mediated by a minuscule
      amount of HEL in the thymus. Conversely, the much larger amounts of HEL in the
      peripheral depot, the eyes, play a minor role if any in the tolerogenic process.
      It is further proposed that a similar mechanism of central tolerance is
      responsible for the immunotolerance against autologous lens crystallins.

PMID- 9761284
TI  - Fluorescence and immunochemical studies of advanced glycation-related lens
      pigments.
AB  - PURPOSE: To establish whether advanced glycation is the major mechanism for
      yellowing of lens proteins. METHODS: Synchronous fluorescence (SF) and
      immunochemical assays were used to study glycation in vitro and in vivo. In the
      in vitro study, advanced glycation end products (AGEs) were prepared and used as
      antigens to induce antibodies to AGEs. The in vitro AGEs and classified nuclear
      cataracts were analyzed by SF and immunochemical assays. RESULTS: In vitro AGEs
      generated from various glycating agents and carrier proteins displayed strong SF
      above 350 nm; the spectra were well resolved with major bands at 380 nm and 420
      nm. Samples from human lenses manifested a band at 395 nm in addition to the two
      bands shown by in vitro AGEs. SF intensity is greater for the water-insoluble
      (WI) than water-soluble (WS) fraction, but both increased with increasing nuclear
      color. The immunoreactivity data also showed that the WI fraction contained more
      AGEs than the WS fraction and that the amount of AGEs increased with increasing
      nuclear color. CONCLUSIONS: Fluorescence and immunoassays indicated that
      pigmented AGEs contributed to yellowing of the crystalline lens nucleus.

PMID- 9761285
TI  - Angiotensin II and insulin induce growth of ciliary artery smooth muscle: effects
      of AT1/AT2 antagonists.
AB  - PURPOSE: Abnormal growth of smooth muscle cells (SMCs) in small arteries of the
      eye is associated with hypertension and diabetes, and the complications that they
      induce. Migration and proliferation of SMCs into the intima are primary
      mechanisms involved in neointima formation. In aortic SMCs, angiotensin II (AII)
      induced proliferation is inhibited by angiotensin type 1 (AT1) receptor
      antagonist. However, in small artery SMCs, in particular in the circulation of
      the eye, the effects of AII on migration and proliferation are unknown. METHODS:
      The effects of AII (10(-6) to 10(-10) M) on migration and proliferation of growth
      arrested SMCs of porcine ciliary arteries were studied in the presence and
      absence of insulin (5 x 10(-10) M) by assaying DNA synthesis (3H-thymidine
      incorporation), cell number, and movement of SMCs across the membrane of a
      modified Boyden chamber. RESULTS: In the absence of insulin, only high
      concentrations (10(-6) to 10(-8) M) of AII induced DNA synthesis and increased
      cell number (P < 0.05); however, in the presence of insulin (5 x 10(-10) M), AII
      induced DNA synthesis and cell number at low concentrations (10(-10) M) and in a
      concentration-dependent manner (P < 0.05). In contrast to proliferation, AII
      induced SMC migration in a concentration-dependent manner in the absence of
      insulin (P < 0.05). The AT1 antagonist CGP48933 (10(-8) to 10(-12) M), but not
      the AT2 antagonist CGP42112 (10(-8) to 10(-12) M), inhibited AII (10(-8) M)
      induced proliferation and migration in a concentration-dependent manner (P <
      0.05). CONCLUSIONS: Our results suggest that AII is a potent mitogen for SMCs of
      ophthalmic arteries, an effect that is enhanced in the presence of insulin, and
      that it may be an important contributor to structural vascular changes in the
      ophthalmic circulation in hypertension associated with non-insulin dependent
      diabetes. The inhibition of AII-induced growth by an AT1 antagonist suggests that
      these drugs may be important therapeutic tools to prevent structural vascular
      changes in the ophthalmic vasculature under these conditions.

PMID- 9761286
TI  - Regulation of corneal endothelial barrier function by adenosine, cyclic AMP, and
      protein kinases.
AB  - PURPOSE: To determine which processes or factors that regulate corneal hydration
      are responsible for the hydration-modulating effects of adenosine. Influx of
      fluid to the stroma and efflux to the aqueous humor are governed, respectively,
      by the imbibition pressure of the stromal matrix and the transendothelial ionic
      gradients determined by the permeability and active transport characteristics of
      this monolayer. The focus of this study was to assess the effects of adenosine on
      these endothelial parameters. METHODS: Isolated corneas freshly dissected from
      rabbit eyes were used throughout. Active ion transport was assessed by
      measurement of 86Rb+ uptake by the endothelial cells of intact corneas incubated
      for 30 minutes in 25 mM HCO3(-)-Ringer with agents promoting corneal
      deturgescence or corneal swelling. Intracellular and extracellular fluid in the
      scraped endothelial cell mass was estimated from simultaneous counts of 3H
      mannitol and 14C-urea, allowing calculation of tissue-to-medium (T-M) ratios of
      86Rb+ in cell water. Permeability of the endothelium was determined by measuring
      the efflux into the superfusate of 5-carboxyfluorescein (CF) applied to the
      stroma of deepithelialized corneas superfused at the endothelial surface with the
      same media described for 86Rb+ uptake. Thickness of these corneas and of others
      fixed for scanning electron microscopy was monitored with a specular microscope.
      RESULTS: In the control medium, 25 mM HCO3(-)-Ringer, 86Rb+ was accumulated to
      yield a T-M ratio of 6.21. Neither adenosine nor other agents that increase
      cyclic adenosine monophosphate (cAMP)--that is, forskolin and dibutyryl cAMP-
      changed this value to a significant extent. Bumetanide had no effect, but ouabain
      caused a decrease in T-M to 1.30, a 79% inhibition. Elimination of Na+ or HCO3-
      also caused marked decreases in uptake. Permeability to CF in control medium was
      3.40 x 10(-4) cm/min. A decrease of more than 20% (P < 0.05) was seen in the
      presence of adenosine and cAMP promoters and also with the protein kinase
      inhibitor H-8, whereas phorbol myristate acetate caused an increase to 4.50 x 10(
      4) cm/min (P < 0.01). Ouabain caused no change, but blocked the effects of
      adenosine. Reducing the Ca2+ concentration of the superfusing medium caused time
      dependent increases in permeability to 4.57 at 15 to 45 minutes and 12.5 at 80 to
      110 minutes. At the earlier time, this increase in permeability could be
      prevented by the addition of adenosine or H-8. Elimination of Na+ or HCO3- ions
      from the medium caused a small decrease in permeability and, like ouabain,
      blocked the effect of adenosine. Changes in thickness of corneas were consistent,
      in most cases, with the observed alterations in 86Rb+ uptake or permeability to
      CF. Scanning electron microscopy showed contraction and rounding of endothelial
      cells in low Ca2+ medium, with stretching of intercellular borders, features that
      were largely eliminated when adenosine was also present. CONCLUSIONS: Adenosine,
      through increasing cAMP, decreases permeability of the corneal endothelium. This
      effect, rather than a change in the active transport (fluid pump) mechanism, is
      responsible for the promotion of deturgescence and maintenance of lower steady
      state thickness of corneas exposed to adenosine. The mechanism may involve the
      phosphorylation state of cytoskeletal proteins and seems to be dependent on an
      undisturbed environment of monovalent ions.

PMID- 9761287
TI  - Mammalian orthologs of C. elegans unc-119 highly expressed in photoreceptors.
AB  - PURPOSE: To characterize orthologous human and murine cDNAs isolated through
      separate screens designed to identify genes expressed preferentially in retina.
      METHODS: By screening bovine, murine, and human retinal cDNA libraries, human UNC
      119 clones of two varieties and a murine cDNA clone corresponding to the most
      abundant human transcript were isolated. Northern blot and reverse transcription
      polymerase chain reaction analyses were used to determine tissue distribution of
      UNC-119 expression; in situ hybridization localized it in retina to
      photoreceptors. Fluorescence in situ hybridization was used to map the human
      structural gene, and its intron- exon boundaries were elucidated by polymerase
      chain reaction amplification and sequencing genomic DNA. RESULTS: UNC-119 was
      expressed at high levels in photoreceptors and at low levels elsewhere. The most
      abundant transcript encoded a protein of 240 amino acids with homology to
      Caenorhabditis elegans UNC-119. Rat and human cDNAs of UNC-119 have been
      previously reported as human retinal gene 4 and rat retinal gene 4 (HRG4 and
      RRG4). An alternative splice form in humans arose from retention of the 3'-most
      intron, seemed to be retina-specific, and encoded a protein of 220 amino acids.
      The human structural gene mapped to 17q 1.2 and comprised at least five exons and
      four introns. A patient with neurofibromatosis type 1, which also maps to
      17q11.2, and cone-rod dystrophy was examined for a deletion of UNC-119 but no
      abnormalities were found. CONCLUSIONS: Given its strong degree of evolutionary
      conservation and abundant and nearly exclusive expression in photoreceptors, it
      is likely that UNC-119 plays an important role in vision and is a strong
      candidate gene for retinal diseases that map to 17q11.2.

PMID- 9761288
TI  - Expression of cathepsin S antisense transcripts by adenovirus in retinal pigment
      epithelial cells.
AB  - PURPOSE: To show the production of sense or antisense transcripts by recombinant
      adenoviruses, to investigate whether the transcripts produced were suitable for
      downregulating the expression of the targeted gene, cathepsin S (CatS), and to
      examine the effect of antisense transcript production on the biologic function of
      retinal pigment epithelial (RPE) cells, including the regulation of endogenous
      aspartic protease expression. METHODS: Ad.MLP.CatSAS, Ad.RSV.CatSAS, and
      Ad.MLP.CatSS recombinant viruses were produced by homologous recombination. The
      recombinant viruses were tested by restriction enzyme digestion to confirm the
      orientation of the inserts. The expression of antisense transcripts was tested by
      northern blot analysis. Western blot analysis was used to study the regulation of
      the endogenous CatS protein in ARPE19 cells. The biologic effect of CatS
      downregulation in ARPE19 cells was tested by proliferation and phagocytosis
      assays, de novo cathepsin D (CatD) synthesis, and measurement of aspartic
      protease activity. RESULTS: After characterization of the recombinant adenovirus
      constructs, the production of antisense and sense CatS transcripts was shown in
      ARPE19 cells. The transcripts appeared at approximately 1.9 kb 48 hours after
      transduction, and the expression of the antisense transcripts was similar in
      constructs carrying either the MLP or the RSV promoter. Western blot analysis
      showed that ARPE19 cells transduced with Ad.MLP.CatSAS and Ad.RSV.CatSAS had no
      detectable CatS. In contrast, there was a strong signal appearing at 24 kDa in
      ARPE19 cells transduced with Ad.MLP.CatSS. ARPE19 cells were transduced to a high
      level. The transduction of ARPE19 cells with the recombinant adenoviruses did not
      affect the morphologic appearance of the cells, their proliferation, or their
      phagocytosing ability. However, ARPE19 cells transduced by Ad.MLP.CatSAS
      recombinant adenovirus showed a significant downregulation of de novo CatD
      synthesis and a twofold decrease in aspartic protease activity. CONCLUSIONS:
      Recombinant adenoviruses were shown to be suitable for producing antisense CatS
      transcripts to modulate endogenous CatS expression in RPE cells. It is proposed
      that CatS may play an important role, directly or indirectly, in the lysosomal
      digestion of outer segments through the regulation of other lysosomal enzyme
      activity, such as the expression of CatD.

PMID- 9761289
TI  - Estrogen receptor expression in bovine and rat retinas.
AB  - PURPOSE: To investigate the expression and distribution of estrogen receptor
      protein and mRNA in bovine and rat retinas. METHODS: Western blot analysis with
      an antiestrogen receptor monoclonal antibody (mAb) was used to detect estrogen
      receptor protein in the bovine retina. Immunohistochemistry with an antiestrogen
      receptor mAb and in situ hybridization with an oligodeoxynucleotide sequence
      coding for estrogen receptor were applied to study the cellular distribution of
      estrogen receptor protein and its mRNA in male bovine retina and rat retina of
      both sexes. RESULTS: Estrogen receptor protein was detected in bovine retina by
      Western blot analysis. Immunohistochemical staining with the antiestrogen
      receptor mAb was widespread throughout the neural retina. Specific staining
      showed extensive distribution localizing in the nerve fiber layer, the ganglion
      cell layer, the inner nuclear layer, and the outer plexiform layer. Retinal
      pigment epithelium and choroid were also stained with the antiestrogen receptor
      mAb. By in situ hybridization, the expression of estrogen receptor mRNA was
      predominantly observed in ganglion cell layer, the inner nuclear layer, and outer
      portion of the outer nuclear layer. No significant difference was found between
      male and female rats in the immunostaining of retinas with the antiestrogen
      receptor mAb. CONCLUSIONS: This study provides the first evidence for the
      presence of estrogen receptor in bovine and rat retinas. Expression of estrogen
      receptor throughout the retina suggests that estrogen may have important
      functions in the retina.

PMID- 9761290
TI  - Vitreous treatment of retinal pigment epithelial cells results in decreased
      expression of FGF-2.
AB  - PURPOSE: Changes in gene expression were investigated after treatment of cultured
      human retinal pigment epithelial (RPE) cells with vitreous. This may have
      implications for proliferative diseases such as proliferative vitreoretinopathy.
      METHODS: Cells were cultured in the presence or absence of human vitreous, and
      gene expression was examined using the differential display polymerase chain
      reaction technique. Differentially expressed RNAs were cloned, screened for
      differential expression, and sequenced. The expression of one of these RNAs (that
      for fibroblast growth factor [FGF]-2/basic FGF) was examined by in situ
      hybridization and ribonuclease protection assays. The level of FGF-2 protein was
      examined by immunoblot analysis. The effects of adding FGF-2 to cells cultured in
      the presence of vitreous were examined. RESULTS: Treatment of low passage human
      RPE cells with 25% vitreous resulted in the epithelial-to-fibroblast-like
      morphologic changes reported by others and in the decreased expression of FGF-2
      mRNA and FGF-2 protein. Addition of FGF-2 to cultures at the same time as
      addition of vitreous prevented some of the effects of vitreous on these cells.
      CONCLUSIONS: Vitreous treatment of RPE cells in culture results in decreased
      expression of FGF-2 mRNA and protein. Because supplementation of FGF-2 prevents
      some of the vitreous-mediated effects, this may indicate that modulation of FGF-2
      levels by the vitreous may play an important role in the phenotypic changes seen
      in RPE cells exposed to vitreous.

PMID- 9761291
TI  - Intact sheets of fetal retina transplanted to restore damaged rat retinas.
AB  - PURPOSE: The aim of this study was to establish a model for morphologic retinal
      reconstruction after destruction of photoreceptors. METHODS: Rat embryos were
      prelabeled by injection of bromodeoxyuridine (BrdU) into timed pregnant rats on 2
      to 6 consecutive days. Pieces of fetal retinas (embryonic day [E] 17 to E22) were
      embedded in growth factor-reduced matrigel for protection and stored in medium on
      ice. With the use of a custom-mnade implantation tool, trimmed embedded pieces
      were placed into the subretinal space of albino rats whose photoreceptors had
      been damaged by continuous exposure to blue light for 3 to 4 days. RESULTS: Donor
      cells were unequivocally identified by the BrdU label. Approximately 25% of
      transplants in the subretinal space developed parallel layers, with photoreceptor
      outer segments facing the host pigment epithelium. Transplants developed rosettes
      if host pigment epithelium had been damaged, if trauma to the donor tissue
      occurred during preparation or transplantation, and if the donor tissue was
      misplaced into the choroid or into the epiretinal space on top of the host
      retina. If the surgery was performed more than 4 weeks after the light damage,
      continued degeneration of the host retina caused secondary pigment epithelium
      damage, and transplants did not develop parallel layers of photoreceptor outer
      segments. CONCLUSIONS: After transplantation to the subretinal space of a
      degenerated retina, gel-protected fetal retina can develop parallel layers and
      photoreceptor outer segments in contact with host pigment epithelium. Transplants
      can develop good fusion with the inner retina of a photoreceptor-deficient
      recipient.

PMID- 9761292
TI  - The role of the p53 protein in the selective vulnerability of the inner retina to
      transient ischemia.
AB  - PURPOSE: To determine whether the p53 protein plays a role in the selective
      vulnerability of the inner retina to transient ischemia. METHODS: Transient
      retinal ischemia was induced using a high intraocular pressure (HIOP) model in
      the Sprague-Dawley rat for 60 minutes. Histopathologic outcome was determined 7
      days after ischemia. In addition, analysis for evidence for apoptosis (TdT-dUTP
      terminal nick-end label [TUNEL] staining) and p53 protein expression
      (immunohistochemistry) was performed at several points during the reperfusion
      period. In a separate set of experiments, wild-type mice and two groups of
      transgenic mice, one homozygous and the other heterozygous for the p53 null gene,
      were also subjected to HIOP for 60 minutes, and histopathology was performed 7
      days later. RESULTS: At 7 days subsequent to 60 minutes of ischemia in the rat,
      there was marked thinning of the inner retinal layers. There were scattered TUNEL
      positive cells within the inner retina, peaking at 24 to 48 hours and persisting
      for at least 7 days. p53 immunochemistry demonstrated elevated protein levels
      within the inner retina; this finding peaked at 24 to 48 hours but was no longer
      present at 4 days after ischemia. TUNEL staining of the inner retina of the mouse
      was most prominent 24 hours subsequent to ischemia but persisted at 48 hours.
      Seven days subsequent to 60 minutes of ischemia in the wild-type and transgenic
      mice, histopathologic evaluation demonstrated preservation of the retinal
      histoarchitecture in the heterozygous group compared with the wild-type or
      homozygous animals. CONCLUSIONS: These data further support the hypothesis that
      the delayed cell death that occurs after transient retinal ischemia is, in part,
      apoptotic. In addition, they suggest a role for the p53 protein in the selective
      vulnerability of the inner retina to transient ischemia. p53 protein may be a
      target for future therapeutic agents in the treatment of disorders of the retina
      where ischemia plays a pathogenetic role.

PMID- 9761293
TI  - Eye elongation during accommodation in humans: differences between emmetropes and
      myopes.
AB  - PURPOSE: The pathophysiology and pathogenesis of myopia are still a matter of
      controversy. Exaggerated longitudinal eye growth is assumed to play an important
      role in the development of myopia. A significant correlation between refraction
      and amount of near-work has been reported. However, current knowledge of changes
      of axial eye length with accommodation is limited because clinical ultrasound
      biometry does not provide the precision and resolution required to thoroughly
      investigate these phenomena. METHODS: Partial coherence interferometry (PCI), a
      noninvasive biometric technique, uses laser light with short coherence length in
      combination with interferometry to achieve precision in the micrometer to
      submicrometer range and resolution of 10 microm. In the present study this
      technique was used to investigate axial eye length changes in 11 emmetropic and
      12 myopic eyes during monocular fixation at the far and near point. In 7
      subjects, the contralateral eye has also been measured to investigate interocular
      differences in eye elongation. RESULTS: All investigated eyes elongated during
      accommodation. This elongation was more pronounced in emmetropes than in myopes
      (P < 0.001). Mean accommodation-induced eye elongations of 12.7 microm (range,
      8.6-19.2 microm) and 5.2 microm (range, 2.1-9.5 microm), corresponding to a
      dioptric change of approximately -0.036 D and -0.015 D, were obtained for
      emmetropes and myopes. No significant difference in accommodative amplitudes
      between groups (5.1 +/- 1.2 D [range, 3.8-7.1 D] versus 4.1 +/- 2.0 D [range, 1.0
      7.1 D]; P = 0.14) was detected. No significant interocular difference in
      accommodation-induced eye elongation was revealed (P = 0.86). Also, a mean
      backward movement of the posterior lens pole of 38 microm (range, 9-107 microm)
      was observed in both study groups. CONCLUSIONS: The detected eye elongation can
      be explained by the accommodation-induced contraction of the ciliary muscle,
      which results in forward and inward pulling of the choroid, thus decreasing the
      circumference of the sclera, and leads to an elongation of the axial eye length.
      Finally, it was demonstrated that PCI, in contrast to clinical ultrasound, is
      capable of characterizing eye length changes during accommodation in humans.

PMID- 9761294
TI  - Extreme responsiveness of the pupil of the dark-adapted mouse to steady retinal
      illumination.
AB  - PURPOSE: To measure the dependence of the size of the pupils of mice on steady
      retinal illumination. METHODS: Anesthetized C57BL/6 mice aged 7 to 8 weeks were
      placed in a ganzfeld chamber in darkness, and in monochromatic (510 nm) and white
      light whose intensity was varied more than 6 log units. The pupils of the mice
      were photographed with an infrared video camera and recorded on videotape and the
      pupil areas determined by digital image analysis of the video recordings.
      RESULTS: Fully dark-adapted murine pupils had an area of 2.29 +/- 0.35 mm2. The
      minimum pupil size at saturating intensity was 0.10 +/- 0.05 mm2. The steady
      state pupil area declined to half its dark-adapted maximum when ganzfeld
      luminance was 10(-5) scotopic candela (scot. cd) per meter squared. Pupil area
      declined to 20% of the dark-adapted magnitude at approximately 10(-3) scot.
      cd/m2. CONCLUSIONS: The mouse pupil can regulate retinal illumination by a factor
      exceeding 20. The neural circuitry that determines steady state murine pupil size
      is extremely sensitive to retinal illumination and under these experimental
      conditions is controlled almost exclusively by rod signals. This follows, because
      the ganzfeld illuminance (10(-5) scot. cd/m2) that causes the pupil to constrict
      to half its dark-adapted value corresponds to only approximately 0.01
      photoisomerization per rod per second, whereas 80% reduction in pupil area occurs
      at approximately 1 photoisomerization per rod per sec. Based on this extreme
      responsiveness to steady illumination, the hypothesis is proposed that the murine
      pupil functions to protect a retinal circuit that can become saturated at
      extremely low photon capture rates. General principles of dark-adapted retinal
      circuitry support the identification of the first three neurons in the circuit as
      the rod, the rod bipolar, and the AII-amacrine. The rod and rod bipolar neurons
      do not approach saturation at the intensities at which the pupil constricts,
      however, and it seems unlikely that the AII-amacrine does. Thus the retinal
      neurons protected from saturation by the mouse pupil constrictions are probably
      ganglion cells with large receptive fields that have sustained responses.

PMID- 9761295
TI  - A new model of proliferative vitreoretinopathy.
AB  - PURPOSE: To design a new model of proliferative vitreoretinopathy (PVR) that
      would not rely on the addition of exogenous cells. The release of endogenous
      cells from surrounding attachments seems to be an early event in the pathogenesis
      of PVR. Because the proteolytic enzyme dispase dissociates tissues, the
      hypothesis was that an intraocular injection of dispase could trigger events that
      would cause PVR. The requirement for a surgical retinal break at the time of
      dispase injection was also examined. METHODS: One eye of Dutch Belted rabbits was
      injected with 0.003 U to 1.0 U dispase in the subretinal space or vitreous
      cavity. Control rabbits received a saline injection. An intentional retinal tear
      was created in animals in some groups. Observations were made for at least 10
      weeks after surgery. RESULTS: Proliferative vitreoretinopathy developed in
      response to subretinal or intravitreal dispase, with or without creation of a
      controlled retinal break. Increased severity of PVR correlated with increasing
      doses of dispase. Evidence of PVR included preretinal membranes, distortion of
      myelin wings and retinal vessels, fixed retinal folds, and traction retinal
      detachment. Proliferative vitreoretinopathy did not develop in saline-treated
      control animals. CONCLUSIONS: Dispase initiated the development of PVR without
      the addition of exogenous cells, growth factors, or cytokines typically found in
      PVR membranes. A cascade of events was probably triggered by dispase, causing
      native cells and factors to produce PVR. The dispase model of PVR was technically
      easy to perform, permitted a clear view of the retina, and had a high success
      rate in development of PVR.

PMID- 9761296
TI  - Polyunsaturated fatty acids are lower in blood lipids of Usher's type I but not
      Usher's type II.
AB  - PURPOSE: Previous studies have shown that persons with retinitis pigmentosa and
      Usher's syndrome have lower blood levels of long-chain polyunsaturated fatty
      acids (PUFAs). In this study, the fatty acid composition of phospholipids from
      plasma and red blood cells (RBCs) was compared in persons with Usher's syndrome
      type I; Usher's syndrome type II; or no retinal disease (control subjects).
      METHODS: Blood was drawn from fasting volunteers and separated into plasma and
      RBCs by centrifugation. Lipids were extracted and phospholipids were obtained by
      thin-layer chromatography. Fatty acid methyl esters were prepared and analyzed by
      gas-liquid chromatography. RESULTS: There were no differences in plasma or RBC
      phospholipid fatty acid composition between control subjects (n = 54) and persons
      with Usher's syndrome type II (n = 20). However, all 20- and 22-carbon PUFA
      levels from RBCs of persons with Usher's syndrome type I were lower than those
      from control subjects and persons with Usher's Syndrome type II. Likewise, plasma
      levels of 20:3n-6, 20: 5n-3, and 22:6n-3 were lower in Usher's syndrome type I
      compared with the control group. In contrast, plasma levels of 18:1n-9 and RBC
      levels of 16:0 and 18:1n-9 were higher in the group with Usher's syndrome type I.
      CONCLUSIONS: Plasma and RBCs from Usher's syndrome type I, but not type II, have
      lower levels of long-chain PUFAs than plasma and RBCs from control subjects.

PMID- 9761297
TI  - Refractive error and age-related maculopathy: the Blue Mountains Eye Study.
AB  - PURPOSE: To assess associations between refractive error (hyperopia, myopia, and
      spherical equivalent [SEq]) and age-related maculopathy (ARM) in an older
      population. METHODS: A population-based survey examined 3654 people aged 49 years
      or older, 82% of whom were permanent residents in an area west of Sydney,
      Australia. Participants had a detailed eye examination, including standardized
      refraction and stereo macular photographs. ARM was diagnosed from blinded
      photographic grading. Autorefractor measurements and subjective refraction were
      used to assess SEq refractive error for each eye in diopters. Mean SEq of the two
      eyes was used to define emmetropia, myopia, and hyperopia in each person.
      RESULTS: After known ARM risk factors (age, sex, ARM family history, current
      smoking) had been adjusted for, no association was found between mean SEq (two
      eyes) and late ARM (odds ratio [OR], 1.0; 95% confidence interval [CI], 0.9-1.1).
      However, a statistically significant increased risk of early ARM was found for
      each diopter of increase in mean SEq (OR, 1.1; CI, 1.0-1.2). In logistic
      regression models, moderate to high hyperopia was significantly associated with
      increased early ARM risk (OR, 2.0; CI, 1.2-3.4). When a generalized estimating
      equation model (GEE), which assessed the relationship at eye level while
      accounting for the correlation between the two eyes, was used, this association
      was marginally insignificant (OR, 1.3; CI, 0.9-1.9). No significant associations
      were found between myopia and any ARM stage with either model. CONCLUSIONS: These
      population-based data suggest a weak association between hyperopia and early ARM.

PMID- 9761298
TI  - Effect of glutamate analogues and inhibitory neurotransmitters on the
      electroretinograms elicited by random sequence stimuli in rabbits.
AB  - OBJECTIVE: To study the origin of the different components of the
      electroretinogram (ERG) elicited by a random binary m-sequence stimulus. METHODS:
      Electroretinograms were recorded from pigmented rabbits before and after the
      injection of glutamate analogues (2-amino-4-phosphono-butyric acid [APB; DL form]
      and cis-2,3-piperidine-dicarboxylic acid [PDA]) and inhibitory neurotransmitters
      (glycine and gamma-aminobutyric acid [GABA]) to abolish the contribution of
      different cell types to the ERG. Two types of stimuli were used: conventional
      full-field stimulation with short- and long-duration flashes and a random binary
      m-sequence of flashes designed to mimic the pseudorandom binary m-sequence
      stimulation used in the multifocal ERG technique. RESULTS: The effects of APB and
      PDA on the first-order kernel of the random ERGs were similar to those on the
      photopic short-flash ERG. Glycine and GABA minimized the oscillatory potentials
      (OPs) of the photopic ERGs, and also reduced the amplitude of the positive wave
      of the first-order kernel slightly but caused a large reduction in the amplitude
      of the second-order kernel. CONCLUSIONS: The data suggest that the ON and OFF
      bipolar cells contribute significantly to the photopic short-flash ERG, as
      previously shown, and to the first-order kernel of the responses elicited by the
      pseudorandom binary sequence stimuli. The second-order kernel and the OPs receive
      a strong contribution from the cells of the inner retinal layers.

PMID- 9761299
TI  - The vertical field border in hemianopia and its significance for fixation and
      reading.
AB  - PURPOSE: The existence of macular sparing, a central seeing area of several
      degrees within the hemianopic field defect, has been controversial for a long
      time, because inaccurate fixation during perimetry can produce ambiguous results.
      The visual field border in hemianopia was studied to examine whether a vertical
      strip of hemifield overlap described in monkeys exists in humans and whether
      additional macular sparing could be found. METHODS: Vertical triplets of dots
      were scanned on the retinas of eight patients (13 eyes) with hemianopia at
      different eccentricity from the vertical meridian during strict simultaneous
      fixation control using a scanning laser ophthalmoscope (SLO). Additionally, eye
      movements were measured by SLO and by an infrared reflection system while
      subjects read texts. RESULTS: Macular sparing of 2 degrees to 5 degrees and
      absence of sparing were observed. The presence and amount of sparing influenced
      fixation behavior, reading performance, and reliability of conventional
      perimetry. The smaller the macular sparing, the less stable the fixation. In the
      absence of sparing, either central unstable fixation with frequent saccades
      toward the hemianopic side or eccentric fixation occurred, resulting in a shift
      of the field defect toward the hemianopic side. A vertical strip of sometimes
      partial perception was found in 12 eyes at 0.5 degrees from the midline.
      CONCLUSIONS: Macular sparing and a slight vertical strip of hemifield overlap
      exists in humans. Adaptive strategies like eccentric fixation and predictive
      saccades improve reading performance and can augment rehabilitation.

PMID- 9761300
TI  - Influences of chorion type on saccadic eye movements in twins.
AB  - PURPOSE: The influence of genetic and prenatal environmental factors on
      characteristics of saccadic performance were evaluated in young monozygotic (MZ)
      twins (8-19 years old) of known chorion type. METHODS: Saccadic eye movements
      were recorded using an infrared system. Saccadic latency, accuracy, and
      parameters of amplitude-peak velocity exponential equation (main sequence) were
      quantified. RESULTS: Intraclass correlations of saccadic parameters differed
      significantly from zero for monochorionic and dichorionic MZ twins. The within
      pair mean squares were significantly less, and intraclass correlations were
      significantly higher in monochorionic than in dichorionic twins for latency and
      were similar for other saccadic parameters (accuracy, slope of main sequence, and
      peak velocity for 15 degrees saccades). CONCLUSIONS: These findings confirmed
      previous reports that saccadic parameters of MZ twins are significantly
      correlated and indicated that similarity of these parameters seen in MZ twins may
      be driven both by genetic and by prenatal environmental factors.

PMID- 9761301
TI  - In vivo demonstration of increased leukocyte entrapment in retinal
      microcirculation of diabetic rats.
AB  - PURPOSE: Leukocytes have been reported to be less deformable and more activated
      in diabetes. It has also been suggested that they cause microvascular occlusions
      that may cause diabetic microangiopathy. This study was designed to evaluate in
      vivo leukocyte dynamics in the retinal microcirculation of diabetic rats.
      METHODS: Streptozotocin (STZ)-induced diabetic rats 4 weeks after diabetes
      induction and spontaneously diabetic Otsuka Long-Evans Tokushima Fatty (OLETF)
      rats with 6 weeks' duration of diabetes were used in this study. Leukocyte
      dynamics were observed with acridine orange digital fluorography, using a nuclear
      fluorescent dye of acridine orange and high-resolution images from a scanning
      laser ophthalmoscope. RESULTS: There was no significant difference in capillary
      leukocyte velocity between the STZ-induced diabetic rats (1.27 +/- 0.12 mm/sec,
      mean +/- SD) and nondiabetic control subjects (1.38 +/- 0.07 mm/sec) or between
      OLETF rats (1.31 +/- 0.17 mm/sec) and the nondiabetic controls, Long-Evans
      Tokushima Otsuka (LETO) rats (1.29 +/- 0.11 mm/sec). In contrast, the density of
      leukocytes trapped in the retinal microcirculation was significantly elevated in
      the STZ-induced diabetic (2.5-fold; P < 0.01) and the OLETF rats (2-fold; P <
      0.01) compared with leukocyte density in the control subjects. CONCLUSIONS:
      Pharmacologically induced and spontaneously diabetic rats showed increased
      leukocyte entrapment in the living retina in the early stages of diabetes. In
      light of the damaging potential of leukocytes, accumulation of leukocytes in
      diabetic retinas from the preretinopathy stage could cause microvascular
      occlusions and dysfunction, in turn causing diabetic retinopathy.

PMID- 9761302
TI  - Matrix metalloproteinases and metalloproteinase inhibitors in choroidal
      neovascular membranes.
AB  - PURPOSE: Matrix metalloproteinases (MMP) are a family of extracellular matrix
      degrading enzymes associated with the development of neovascularization. To
      investigate the possible role of these enzymes in choroidal neovascularization,
      the mRNA expression of MMPs and tissue inhibitors of metalloproteinases (TIMPs)
      were analyzed in subfoveal fibrovascular membranes from patients with age-related
      macular degeneration (AMD). METHODS: Surgically removed subfoveal fibrovascular
      membranes from five eyes were analyzed for the expression of MMP and TIMP mRNA.
      In situ hybridization anti-sense and sense riboprobes were generated using DNA
      complementary to human collagenase (MMP-1), 72 kDa gelatinase (MMP-2),
      stromelysin (MMP-3), 92-kDa gelatinase (MMP-9), TIMP-1, TIMP-2, and TIMP-3.
      Vascular endothelial cells were detected using immunostaining for von Willebrand
      factor. RESULTS: MMP-2 and MMP-9 mRNA were detected in all specimens. Most of the
      membranes also expressed TIMP-1 and TIMP-3 mRNA, and two of the membranes
      expressed TIMP-2 mRNA. MMP-2, TIMP-1, and TIMP-2 mRNA had a similar overall
      distribution that was relatively uniform within the vascularized membrane stroma.
      MMP-2 expression appeared to be localized mainly to the vascular endothelial
      cells, whereas TIMP-1 and TIMP-3 were detected in other cell types such as
      fibroblastlike cells. MMP-9 expression was distinctly expressed by cells at the
      margins of the membranes and often in proximity to a thickened Bruch's membrane
      like layer under the retinal pigment epithelial cells. TIMP-3 mRNA was strongly
      expressed within the retinal pigment epithelial cell layer and also in the stroma
      of one membrane. None of the membranes showed detectable MMP-1 or MMP-3
      expression. CONCLUSIONS: The results support a role for MMPs in the development
      of choroidal neovascularization in AMD. The localization of MMP-2 and MMP-9 to
      the areas of new vessel formation and to the enveloping Bruch's-like membrane,
      respectively, suggests that MMP-2 and MMP-9 may be cooperatively involved in the
      progressive growth of choroidal neovascular membranes in AMD.

PMID- 9761303
TI  - Choroidal blood flow in AMD.

PMID- 9761304
TI  - Research on the human brain in an epilepsy surgery setting.
AB  - Recent advances in our understanding of the fundamental mechanisms of epilepsy
      have derived, to a large extent, from improvements in designing parallel human
      and animal studies. This is the result not only of better animal models of human
      epileptic phenomena, but of an increasing ability to carry out detailed invasive
      studies on patients in the course of surgical treatment for medically refractory
      epilepsy. In addition to interictal and ictal video-EEG recordings with chronic
      depth and subdural electrodes, it is also possible to sample single-unit activity
      with chronically implanted microelectrodes, and measure constituents of
      extracellular fluid with chronically implanted microdialysis probes, using
      protocols that in the past were possible only in the experimental animal
      laboratory. Subsequent surgical resection provides tissue that can be used for
      electrophysiological, morphological, biochemical, and molecular biological
      investigations. Patients in epilepsy surgery facilities represent a precious
      resource for research that should be utilized to the fullest extent possible by
      basic scientists interested in mechanisms of epilepsy. It is particularly
      important that invasive research be pursued now, because improved diagnostic
      technology is greatly reducing the need for chronic intracranial electrode
      recordings, and surgical approaches that do not yield tissue could be used more
      commonly in the future. Therefore, the capacity to carry out invasive research in
      the context of epilepsy surgery may diminish greatly over time. To take full
      advantage of these opportunities, carefully designed iterative experimental
      protocols are necessary to characterize abnormalities in the human epileptic
      brain, to create appropriate experimental animal models to study these phenomena
      in greater detail, and to return to the human brain to validate the clinical
      relevance of observations made on animals. It is also important, however, to
      recognize certain unavoidable limitations of human research, including ethical
      considerations, variability inherent in the clinical setting, imprecision in
      defining target areas, lack of control data, and small subject numbers, which
      continue to make animal investigations essential to the achievement of our goals
      of defining fundamental mechanisms of human epileptic phenomena.

PMID- 9761305
TI  - Tuberous sclerosis-related gene expression in normal and dysplastic brain.
AB  - Cortical dysplasia (CD) broadly defines a complex cerebral malformative lesion
      associated clinically with intractable, pharmacoresistant epilepsy (including
      infantile spasms), especially in infants and children. In CD, the spectrum of
      structural brain abnormalities includes (at a minimum) neuronal dyslamination and
      (in severe cases) neuronal cytomegaly with cytoskeletal alterations and the
      presence of gemistocyte-like 'balloon cells'. In some CD variants, the
      neuropathological features are essentially indistinguishable from those of a
      tuber of tuberous sclerosis (TSC). Two genes associated with the autosomal
      dominant, multi-system disorder TSC have recently been cloned: TSC2 (on
      chromosome 16p13.3) encodes the protein tuberin and TSC1 (on 9q34) encodes
      hamartin. Tuberin has been immunolocalized to neurons and possibly astrocytes in
      normal brain and CD/TSC tubers, and is widely expressed in normal viscera; loss
      of heterozygosity and tissue culture studies suggest it functions as a growth
      suppressor. The TSC1 gene has been cloned within the last year and hamartin as
      yet has no well-defined cellular function, though its protein product may also
      function as a growth suppressor. This article focuses on the cellular
      pathogenesis of CD and TSC brain lesions and how the two may be biologically
      related. Studies of how TSC1 and TSC2 function in normal and dysplastic cerebral
      neocortex may provide a paradigm for understanding the neurobiology of other
      genes that determine epilepsy-associated cerebral malformations (e.g.
      lissencephaly, double cortex).

PMID- 9761306
TI  - Glutamate receptor mechanisms in human epileptic dysplastic cortex.
AB  - Developmental disorders of neuronal migrations in the human brain are referred to
      as 'cortical dysplasia', and current knowledge of cortical dysplasia is limited
      to varied pathologic descriptions which lack specific investigations of glutamate
      receptor mechanisms. In this study, immunocytochemistry was used to study the
      expressions of glutamate receptor subunit proteins for NMDAR2A/B, NMDAR1 and AMPA
      Glu-R2/3 in human brain resected for intractable epilepsy associated with
      cortical dysplasia. Seventeen patients were studied with batch-matched glutamate
      subunit reagents on adjacent 30-microm sections. The most striking microscopic
      abnormalities identified in cresylecht violet stains were cortical
      dyslaminations, disoriented neurons, and unexpectedly, very dark Nissl body
      staining of those dysplastic neurons. NMDAR2A/B intensely labeled dysplastic
      neurons, showing staining in both the cell bodies and dendritic profiles.
      However, non-dysplastic neurons were not immunoreactive to NMDAR2A/B. Dysplastic
      neurons were also labeled by antibodies selective to NMDAR1. Both dysplastic
      neurons and non-dysplastic neurons were immunoreactive to AMPA GluR2/3. Our
      results suggest that the epileptic hyperexcitability of dysplastic cortical
      regions may result, at least in part, from the heteromeric coassembly and
      expressions of NMDAR2A/B subunits with selectively expressed NMDAR1 splice
      variants in dysplastic neurons. AMPA receptors are probably also essential but
      not sufficient to explain the 'epileptic' properties of these dysplastic neurons.
      A longer, detailed report of some of these findings have been previously
      published (Ying et al., 1998. J. Neuropathol. Exp. Neurol. 57, 47-62).

PMID- 9761307
TI  - Immunocytochemical investigation on dysplastic human tissue from epileptic
      patients.
AB  - In this report we describe three patients with developmental cortical
      abnormalities (generally referred as cortical dysplasia), revealed by MRI and
      operated on for intractable epilepsy. Tissue, removed for strictly therapeutic
      reasons, was defined as the epileptogenic area by electroclinical data and stereo
      EEG (SEEG) recordings. Tissue samples were processed initially for histology, and
      selected sections were further processed for immunocytochemical investigation in
      order to determine whether the region of cortical dysplasia was co-extensive with
      the epileptogenic area. In two patients with nodular heterotopia, disorganized
      aggregates of neurons (as revealed by neuronal cytoskeletal markers) were found
      within the nodules. Both pyramidal and local circuit neurons were present in the
      nodules, but no reactive gliosis was present. When nodules reached the cortex,
      the cortical layers were disrupted. In the patient with localized cortical
      dysplasia, a complete disorganization of the cortical lamination was found, and
      numerous neurons were also present in the white matter. Disoriented pyramidal
      neurons weakly labelled with cytoskeletal neuronal markers were also present but
      no cytomegalic cells were found. One of the patients with nodular heterotopia
      underwent only partial resection of both the 'epileptogenic area' and of the
      lesion; this patient still presents with seizures. The other patient with nodular
      heterotopia is seizure-free after a complete lesionectomy and excision of the
      epileptogenic area. The third patient, with focal cortical dysplasia, had two
      surgeries; she became seizure-free only after the excision of the epileptogenic
      area detected by SEEG recording. The present data suggest that the dysplastic
      areas identified by MRI should not be considered as the only place of origin of
      the ictal discharges. From the neuropathological point of view, the focal
      cortical dysplasia can be considered as a pure form of migrational disorder.
      However, the presence of large aggregates of neurons interspersed within the
      white matter, in the subcortical nodular heterotopia, suggests that a defect of
      neuronal migration could be associated with an exuberant production of
      neuroblasts and/or a disruption of mechanisms for naturally occurring cell death.

PMID- 9761308
TI  - Altered connections between neocortical and heterotopic areas in
      methylazoxymethanol-treated rat.
AB  - We are currently investigating various treatments which could determine, in the
      rat brain, structural abnormalities mimicking those reported in human brain
      dysgeneses. We can induce the formation of neuronal heterotopia in the progeny of
      rats by means of a double injection of the cytotoxic agent methylazoxymethanol
      acetate (MAM) on embryonic day 15. We have now investigated the anatomical
      connections of these heterotopia by means of anterograde and retrograde tract
      tracing techniques. The induced heterotopia along the border of the lateral
      ventricles shared common anatomical features with the periventricular nodules in
      human periventricular or subcortical nodular heterotopia (PNH). The tract tracing
      data demonstrated the existence of reciprocal connections between the neuronal
      heterotopia and the ipsilateral and contralateral cortical areas, and the
      presence of abnormal cortico-hippocampal and cortico-cortical connections. On the
      basis of the connectivity patterns, it may be speculated that some cells in the
      heterotopia could be neurons originally committed to the cortex, that were
      interrupted in their migration by the MAM treatment. Given the common
      morphological features seen in human PNH and MAM-induced brain heterotopia, the
      anatomical and developmental analysis of MAM-treated rats may shed light on the
      mechanisms by which human brain dysgeneses develop in human patients.

PMID- 9761309
TI  - In utero irradiation of rats as a model of human cerebrocortical dysgenesis: a
      review.
AB  - Certain developmental abnormalities of the cerebral cortex are closely associated
      with epilepsy in humans. Exposure of fetal rats to external gamma-irradiation
      produces diffuse cortical dysplasia and neuronal heterotopia. These abnormalities
      are the result of radiation-induced cell death coupled with continued cortical
      development in an altered cellular environment. In vivo electroencephalography
      studies in these animals have revealed an increased propensity for electrographic
      seizures in the presence of the sedating agents, acepromazine and xylazine. In
      vitro neocortical slices containing dysplastic cortex demonstrate enhanced
      excitability, as compared to control neocortex, when inhibition that is mediated
      by the A-type gamma-amino butyric acid receptor is blocked with bicuculline
      methiodide. In utero irradiation of rats produces structural changes that mimic
      some aspects of cerebral dysgenesis in humans and results in physiologic changes
      that increase the animals' propensity for seizures. Similarities and differences
      between the animal model and the human syndromes are discussed.

PMID- 9761310
TI  - Excitability changes in freeze-induced neocortical microgyria.
AB  - A freezing probe was placed on the skull of postnatal day (PN) 1 rats to induce
      formation of a cerebrocortical microsulcus. Experimental studies were performed
      on PN days 21-24. At that time point, Nissl-stained sections revealed the
      presence of a microsulcus similar to that described in human dysplastic cortex.
      Immunocytochemical staining for parvalbumin, calretinin and calbindin indicated a
      significant decrease in the number of immunoreactive neurons within the
      microsulcus and non-significant decreases in regions adjacent to the microsulcus.
      Staining for the glial markers GFAP and vimentin was increased near the
      microsulcus. Using in vitro brain slices, recordings were made in cortex adjacent
      to the microsulcus. Epileptiform activity was observed in response to electrical
      stimulation near the microsulcus. Analysis of the voltage dependence of evoked
      epileptiform discharges suggested the presence of an inhibitory component. As
      previously observed in non-lesioned animals, bath application of 4-aminopyridine
      induced bicuculline-sensitive spontaneous burst discharges in the presence of
      excitatory amino acid antagonists. These results suggest that cortical freeze
      lesions associated with abnormal neuronal migration produce a chronic
      hyperexcitable state. The findings are consistent with a mechanism involving an
      alteration, not loss, of inhibition in this model.

PMID- 9761311
TI  - Inhibitory function in two models of chronic epileptogenesis.
AB  - Although drug-induced disinhibition is a potent method for producing acute
      epileptogenesis, data with respect to possible disorders of GABAergic inhibitory
      function in models of chronic epilepsy are incomplete and inconsistent. We
      examined rat models of cortical post-traumatic epilepsy, and epileptogenic
      cortical microgyri. Results suggest enhanced rather than decreased inhibitory
      function in cortical networks in these preparations. In brain slices from
      epileptogenic chronically isolated cortex, the frequency of spontaneous
      inhibitory postsynaptic currents (sIPSCs) and miniature (m)IPSCs in layer V
      pyramidal neurons is increased compared to control. In the epileptogenic zone
      adjacent to the microgyrus, both spontaneous and stimulus-induced IPSCs are
      larger in amplitude than control, and the frequency of sIPSCs is more dependent
      upon glutamatergic excitation of interneurons than in control layer V neurons of
      homotopic cortex. Immunocytochemical studies show that there is enhanced
      immunoreactivity for several proteins in GABAergic interneurons of chronic
      cortical isolations, and suggest that there may be sprouting of GABAergic axons
      in the area of injury. This conclusion is supported by anatomic data showing an
      approximate doubling of the number of presumed inhibitory synapses on somata of
      layer V pyramidal neurons. These anatomic findings are consistent with the
      increased frequency of mIPSCs on these neurons. Inhibition is robust in both of
      these chronic models of epileptogenesis. Increased inhibitory electrogenesis
      might be pictured as part of the epileptogenic process, e.g. a mechanism for
      synchronizing the discharge of pyramidal neurons, or as a compensatory mechanism
      that might prevent the development of abnormal activities in some cases, or limit
      the intensity of epileptogenesis in others.

PMID- 9761312
TI  - Interneurones are not so dormant in temporal lobe epilepsy: a critical
      reappraisal of the dormant basket cell hypothesis.
AB  - One axiom at the basis of epilepsy research is that there exists an imbalance
      between excitation and inhibition. This abnormality can be achieved by an
      increase of excitation on principal cells, a decreased inhibition (i.e.
      disinhibition) or both. This review focuses on dysfunction of inhibition, and in
      particular on the 'dormant basket cell hypothesis'. This hypothesis states that,
      (1) interneurones are functionally disconnected from excitatory afferents,
      resulting in hyperexcitability of principal neurones and loss of paired pulse
      inhibition, (2) when properly activated, interneurones can still perform their
      task, i.e. suppress epileptiform activity and restore paired pulse inhibition.
      The aim of this review is to discuss the evidence in support of the 'dormant
      basket cell hypothesis'. We will first discuss the rationale underlying the
      hypothesis and the criteria needed to validate the hypothesis. We will then show
      that, (1) the key experimental data offered in support of the hypothesis
      (Bekenstein and Lothman, 1993. Dormancy of inhibitory interneurones in a model of
      temporal lobe epilepsy. Science 259, 97-100; Sloviter, 1991. Permanently altered
      hippocampal structure, excitability, and inhibition after experimental status
      epilepticus in the rat: the 'dormant basket cell' hypothesis and its relevance to
      temporal lobe epilepsy. Hippocampus 1, 41-66) are difficult to interpret, and (2)
      recent recordings from interneurones in epileptic tissue argue against the
      hypothesis. The 'dormant basket cell hypothesis' is then discussed in the broader
      context of disinhibition.

PMID- 9761313
TI  - 'Dormant' inhibitory neurons: do they exist and what is their functional impact?
AB  - The concept of dormant interneurons is proving to be hard to define precisely. We
      argue here that the term is best used as an operational description of
      interneurons which are not lost from the epileptic brain, but which fail to
      perform adequately. We present evidence for the existence of functionally dormant
      interneurons in the tetanus toxin model of chronic epilepsy, and we explore the
      roles of a partial dormancy (and also of charge-screening) in the acute low
      magnesium model of epilepsy.

PMID- 9761314
TI  - GABA(A) receptor function in epileptic human dentate granule cells: comparison to
      epileptic and control rat.
AB  - Using patch clamp recording techniques in dentate granule cells (DGCs) isolated
      from patients undergoing temporal lobectomy for intractable epilepsy, we
      investigated basic properties of GABA(A) receptors (GABA(A)Rs) and
      pharmacological sensitivity of GABA-evoked currents to modulation by zinc and
      benzodiazepines (BZ). Properties of human DGC GABA(A)Rs were compared to DGC
      GABA(A)R properties in control and epileptic rats. Blockade of GABA evoked
      currents by zinc was significantly enhanced in epileptic human relative to
      control rat DGCs. Augmentation of the GABA(A)R current by the non-subunit
      selective BZ agonist, clonazepam (CNZ) and by the BZ1 specific agonist, zolpidem
      (ZOL), were not significantly different in human DGCs relative to control or
      epileptic rat. GABA potency was significantly higher in epileptic human DGCs than
      in control or epileptic rat DGCs. The significantly enhanced efficacy of zinc in
      blocking GABA currents in epileptic human DGCs mirrors that seen in epileptic rat
      DGCs, and was coupled with mossy fiber sprouting evident in both epileptic human
      and rat dentate gyrus. The aberrant mossy fibers provide a novel zinc delivery
      system within the epileptic dentate gyrus. The mossy fiber release of zinc onto
      DGCs coupled with the enhanced zinc sensitivity of GABA(A)Rs in epileptic DGCs,
      may lead to 'dynamic disinhibition' which could compromise inhibitory efficacy in
      the epileptic rat and human hippocampus.

PMID- 9761315
TI  - Expression of GABA(A) receptor subunits in the hippocampus of the rat after
      kainic acid-induced seizures.
AB  - The GABA(A) receptor is a ligand gated chloride channel consisting of five
      membrane spanning proteins for which 13 different genes have been identified in
      the mammalian brain. The present review summarizes recent work from our
      laboratory on the characterization of the immunocytochemical distribution of
      these GABA(A) receptor subunits in the rat brain and changes in immunoreactivity
      and mRNA expression after kainic acid-induced status epilepticus. A heterogeneous
      distribution of immunoreactive GABA(A) receptor subunits was observed. The most
      abundant ones were: alpha1, alpha2, alpha4, alpha5, beta2, beta3, gamma2, and
      delta. Alpha1, beta2, and gamma2 were about equally distributed in all subfields
      of the hippocampus; alpha4- and delta-subunits were preferentially found in the
      dentate molecular layer and in CA1; alpha2 was localized to the dentate molecular
      layer and CA3; alpha5 was found in the dendritic areas of CA1 to CA3; and beta1
      was preferentially seen in CA2. Alpha1, beta2, gamma2 and delta were highly
      concentrated in interneurons. Kainic acid-induced seizures caused acute and
      chronic changes in the expression of mRNAs and immunoreactive proteins. Acute
      changes included decreases in alpha2, alpha5, beta1, beta3, gamma2 and delta mRNA
      levels (by about 25-50%), accompanied by increases (by about 50%) in alpha1,
      alpha4, and beta2 messages in granule cells (after 6-12 h). Chronic changes,
      characterized by losses in mRNA and immunoreactive proteins in CA1 and CA3, are
      undoubtedly due to seizure-related cell damage. However, compensatory expression
      of alpha2 and beta3 subunits, especially in CA3b/c, was observed. Furthermore,
      increases in mRNAs and immunoreactive proteins were seen for alpha1, alpha2
      alpha4, beta1, beta2, beta3 and gamma2 in granule cells and in the molecular
      layer of the dentate gyrus at 7-30 days after kainic acid injection. The changes
      in the expression of GABA(A) receptor subunits, observed in practically all
      hippocampal subfields, may reflect altered GABA-ergic transmission during
      development of the epileptic syndrome. Increased expression of GABA(A) receptor
      subunits in the dendritic field of granule cells and CA3 suggest that GABA-ergic
      inhibition may be augmented at these levels. However, the lasting preservation of
      alpha1-, beta2-, and gamma2-subunits in interneurons could provide a basis for
      augmented inhibition of GABA-ergic interneurons, leading to net disinhibition.

PMID- 9761316
TI  - Transcripts of the transposon mariner are present in epileptic brain.
AB  - Mobile genetic elements termed transposons have been increasingly implicated in
      human disease. The small transposon mariner is widespread within non-vertebrate
      genomes and causes mutation by replication, excision, and insertion of itself
      without an RNA intermediate. We find that human DNA contains about 60 copies of
      this gene. Mariner transcripts are abundant in RNA prepared from sclerotic
      epileptic hippocampi. In contrast, typically no mariner-specific RNA is detected
      in non-sclerotic hippocampi from other epileptic patients or from autopsies. A
      complete but non-functional copy was obtained using rapid amplification of cDNA
      ends (RACE). This human mariner transcript is approximately 45% homologous to a
      functional counterpart active in Drosophila, with a coding region of 1035 bases
      flanked by 32 base inverted terminal repeats. The differential expression of
      mariner transcripts within sclerotic hippocampi suggests the probable activity of
      an autonomous element which by mutating critical genes could establish an
      epileptogenic substrate in the hippocampus.

PMID- 9761317
TI  - Hippocampal AMPA and NMDA mRNA levels and subunit immunoreactivity in human
      temporal lobe epilepsy patients and a rodent model of chronic mesial limbic
      epilepsy.
AB  - This study compared temporal lobe epilepsy patients, along with kindled animals
      and self sustained limbic status epilepticus (SSLSE) rats for parallels in
      hippocampal AMPA and NMDA receptor subunit expression. Hippocampal sclerosis
      patients (HS), non-HS cases, and autopsies were studied for: hippocampal AMPA
      GluR1-3 and NMDAR1&2b mRNA levels using in situ hybridization: GluR1, GluR2/3,
      NMDAR1, and NMDAR2(a&b) immunoreactivity (IR); and neuron densities. Similarly,
      spontaneously seizing rats after SSLSE, kindled rats, and control animals were
      studied for: fascia dentata neuron densities: GluR1 and NMDAR2(a&b) IR; and neo
      Timm's staining. In HS and non-HS cases, the mRNA hybridization densities per
      granule cell, as well as molecular layer IR, showed increased GluR1 (relative to
      GluR2/3) and increased NMDAR2b (relative to NMDAR1) compared to autopsies.
      Likewise, the molecular layer of SSLSE rats with spontaneous seizures
      demonstrated more neo-Timm's staining, and higher levels of GluR1 and NMDAR2(a&b)
      IR compared to kindled animals and controls. These results indicate that
      hippocampal AMPA and NMDA receptor subunit mRNAs and their proteins are
      differentially increased in association with spontaneous, but not kindled,
      seizures. Furthermore, there appears to be parallels in fascia dentata AMPA and
      NMDA receptor subunit expression between HS (and non-HS) epileptic patients and
      SSLSE rats. This finding supports the hypothesis that spontaneous seizures in
      humans and SSLSE rats involve differential alterations in hippocampal ionotrophic
      glutamate receptor subunits. Moreover, non-HS hippocampi were more like HS cases
      than hippocampi from kindled animals with respect to glutamate receptors;
      therefore, hippocampi from kindled rats do not accurately model human non-HS
      cases, despite some similarities in neuron densities and mossy fiber axon
      sprouting.

PMID- 9761318
TI  - Supragranular mossy fiber sprouting is not necessary for spontaneous seizures in
      the intrahippocampal kainate model of epilepsy in the rat.
AB  - In a previous study, we suggested a dissociation between spontaneous recurrent
      epileptic seizures (SRS) and hippocampal supragranular mossy fiber sprouting
      (MFS) in the pilocarpine model of epilepsy (PILO). One possible explanation,
      would be that SRS in the PILO model do not originate in the hippocampus and thus
      would not depend on MFS. In the present study, we investigated whether MFS is
      necessary for the SRS that develop after a small intrahippocampal dose of kainic
      acid (KA), a model where seizures are more likely to start in the hippocampus.
      Intrahippocampal injections of KA were performed in rats, with and without the
      concomitant administration of cycloheximide (CHX) (0.5 microg of KA and 6 microg
      of CHX). After injection, recording electrodes were positioned in the same
      stereotaxic location. Here again, CHX was able to completely block (5/8 animals)
      MFS, visualized by neo-Timm staining, without altering the frequency and
      intensity of spontaneous ictal and interictal EEG events. From these data, we can
      conclude that, in the intra-hippocampal KA model, MFS is not necessary for the
      occurrence of ictal events. We suggest that CHX can be used together with classic
      epileptogenic agents, as a means to study temporal lobe epilepsy (TLE) without
      the contributing effect of MFS--as seen in TLE patients with mass lesions in the
      lateral temporal lobe.

PMID- 9761319
TI  - Interaction between superficial layers of the entorhinal cortex and the
      hippocampus in normal and epileptic temporal lobe.
AB  - The entorhinal cortex (EC) is a major gateway for sensory information into the
      hippocampal formation. The information flow from layer II and III of the medial
      EC to the hippocampus is regulated in a frequency dependent manner. Spread of low
      Mg2+-induced epileptiform activity from EC to hippocampus differs in slices
      obtained from normal and kindled rats, and in adult versus juvenile rats. In
      slices from normal rats, low Mg2+-induced epileptiform activity in the EC had
      only moderate effects on the areas CA3 and CA1, apparently gated by powerful
      inhibition in the dentate gyrus. In slices from kindled rats, and from juvenile
      rats, there is facilitated propagation of the seizure-like events and late
      recurrent discharges through the EC-hippocampal slice. Temporal lobe epilepsy is
      associated with selective lesions in layer III of the medial EC. Such loss of
      layer III cells of the medial EC during epilepsy may contribute to the
      disturbance of frequency dependent information flow from the EC to the
      hippocampus, and, therefore, to the cognitive impairments associated with these
      disorders.

PMID- 9761320
TI  - Functional anatomy of limbic epilepsy: a proposal for central synchronization of
      a diffusely hyperexcitable network.
AB  - The limbic/mesial temporal lobe epilepsy syndrome has been defined as a focal
      epilepsy, with the implication that there is a well defined focus of onset,
      traditionally centered around the hippocampus. The pathology of the hippocampus
      in this syndrome has been well described and a number of physiological
      abnormalities have been defined in this structure in animal models and humans
      with epilepsy. However, anatomical and physiological abnormalities have also been
      described in other limbic sites in this form of epilepsy. Previous studies have
      shown broadly synchronized or multifocal seizure onset within the limbic system
      of the animal models and human patients. We hypothesized that the epileptogenic
      circuit for the initiation of seizures was distributed throughout the limbic
      system with a possible central synchronizing process. In vitro studies showed
      that multiple limbic sites in epileptic animals (hippocampus, entorhinal cortex,
      piriform cortex and amygdala) have epileptiform changes with prolonged
      depolarizations and multiple superimposed action potentials. In vivo studies
      revealed that thalamic stimulation yields short latency excitatory responses in
      the entorhinal cortex and hippocampus. In addition, in epileptic animals,
      thalamic stimulation caused epileptiform responses in the hippocampus. Based on
      the findings of this study and on previous anatomy and physiology reports, we
      hypothesize that the process of seizure initiation involves broad circuit
      interactions involving multiple independent limbic structures, and that the
      midline thalamus may act as a physiological synchronizer. We offer a new proposal
      for the functional anatomy of limbic epilepsy that takes widespread
      hyperexcitability in the limbic system and the potential for thalamic
      synchronization into consideration.

PMID- 9761321
TI  - Local cerebral glucose utilization in adult and immature GAERS.
AB  - In the present study, we compared the basal local cerebral metabolic rates for
      glucose (LCMRglcs) both in Wistar rats with genetic absence epilepsy (GAERS:
      genetic absence epilepsy rats from Strasbourg) and in control non epileptic (NE)
      rats selected in our breeding colony. LCMRglc was measured both in immature rats
      at postnatal day 21 (P21) at which age no spontaneous spike-and-wave discharges
      can be recorded in GAERS and at the adult age (6 months) when GAERS fully express
      thalamo-cortical spike-and-wave discharges recorded on the EEG. LCMRglcs were
      measured in 24 structures by the quantitative [14C]2-deoxyglucose
      autoradiographic technique. In adults GAERS, LCMRglc underwent a widespread
      increase recorded in all brain structures except in mediodorsal and ventromedian
      thalamus, and in the nucleus accumbens. These metabolic increases ranged from 17
      to 50% over control levels in adult NE rats. In P21 GAERS, LCMRglc was similar to
      that of P21 NE rats in 16 areas. It increased over control levels of NE rats in
      two groups of structures. Metabolic increases were recorded in four limbic
      structures (entorhinal and piriform cortices, hippocampus and basolateral
      amygdala) where no spike-and-wave discharges were recorded in adult GAERS.
      Increases in LCMRglcs were also located in the substantia nigra pars reticulata,
      superior colliculus and globus pallidus which are structures involved in the
      control of seizure activity. In conclusion, our data suggest that the
      consequences of the genetic mutation(s) underlying the cellular and molecular
      events responsible for the expression of spike-and-wave discharges in adult GAERS
      is (are) able to increase metabolic activity in both limbic structures and the
      nigral inhibitory system before the occurrence of spike-and-wave discharges.

PMID- 9761322
TI  - The role of basal ganglia in the control of generalized absence seizures.
AB  - During the last two decades, evidence has accumulated to demonstrate the
      existence, in the central nervous system, of an endogenous mechanism that exerts
      an inhibitory control over different forms of epileptic seizures. The substantia
      nigra and the superior colliculus have been described as key structures in this
      control circuit; inhibition of GABAergic neurons of the substantia nigra pars
      reticulata results in suppression of seizures in various animal models of
      epilepsy. The role in this control mechanism of the direct GABAergic projection
      from the striatum to the substantia nigra and of the indirect pathway, from the
      striatum through the globus pallidus and the subthalamic nucleus, was examined in
      a genetic model of absence seizures in the rat. In this model, pharmacological
      manipulations of both the direct and indirect pathways resulted in modulation of
      absence seizures. Activation of the direct pathway or inhibition of the indirect
      pathway suppressed absence seizures through disinhibition of neurons in the deep
      and intermediate layers of the superior colliculus. Dopamine D1 and D2 receptors
      in the nucleus accumbens, appear to be critical in these suppressive effects.
      Along with data from the literature, our results suggest that basal ganglia
      circuits play a major role in the modulation of absence seizures and provide a
      framework to understand the role of these circuits in the modulation of
      generalized seizures.

PMID- 9761323
TI  - Spatio-temporal distribution of epileptiform activity in slices from human
      neocortex: recordings with voltage-sensitive dyes.
AB  - The spatio-temporal distribution of epileptiform activity was investigated in
      slices from human temporal neocortex resected during epilepsy surgery. Activity
      was recorded by use of a voltage-sensitive dye and an optical recording system.
      Epileptiform activity was induced with 10 microM bicuculline and electrical
      stimulation of layer I. In 10 slices from six patients investigated, epileptiform
      activity spread across most of the slice. Largest amplitudes were located in
      layer II/III. Epileptiform activity was characterized by long-lasting potentials
      with slow rising phases and a low velocity of spread in the horizontal direction
      (0.044 m/s). This spatio-temporal pattern of epileptiform activity in human
      slices was similar to that found previously in neocortical slices from guinea
      pigs with bicuculline. In four of nine human slices investigated under control
      bath conditions (in non-epileptogenic medium), the spatio-temporal activity
      patterns were similar to those of guinea pigs in non-epileptogenic medium. In the
      remaining five human slices, however, the spread in the horizontal direction was
      significantly larger (4188 microm) in non-epileptogenic medium than that found in
      slices from guinea pigs (2171 microm). Activity in human slices showing such
      'wide spread' in control bath conditions occasionally had characteristic features
      of epileptiform activity. Further work will have to clarify whether these
      epileptiform features reflect intrinsic epileptiform properties in human tissue
      slices.

PMID- 9761324
TI  - Amygdala damage in experimental and human temporal lobe epilepsy.
AB  - The amygdala complex is one component of the temporal lobe that may be damaged
      unilaterally or bilaterally in children and adults with temporal lobe epilepsy
      (TLE) or following status epilepticus. Most MR (magnetic resonance) imaging
      studies of epileptic patients have shown that volume reduction of the amygdala
      ranges from 10-30%. In the human amygdala, neuronal loss and gliosis have been
      reported in the lateral and basal nuclei. Studies in rats have more specifically
      identified the amygdaloid regions that are sensitive to status epilepticus
      induced neuronal damage. These areas include the medial division of the lateral
      nucleus, the parvicellular division of the basal nucleus, the accessory basal
      nucleus, the posterior cortical nucleus, and portions of the anterior cortical
      and medial nuclei. Otherwise, other amygdala nuclei, such as the magnocellular
      and intermediate divisions of the basal nucleus and the central nucleus, remain
      relatively well preserved. Amygdala kindling studies in rats have shown that the
      density of a subpopulation of GABAergic inhibitory neurons that also contain
      somatostatin may be reduced even after a low number of generalized seizures.
      While analyses of histological sections and MR images indicate that in
      approximately 10% of TLE patients, seizure-induced damage is isolated to the
      amygdala, more often amygdala damage is combined with damage to the hippocampus
      and/or other brain areas. Moreover, recent data from rodents and nonhuman
      primates suggest that structural and functional alterations caused by seizure
      activity originating in the amygdala are not limited to the amygdala itself, but
      may also affect other temporal lobe structures. The information gathered so far
      on damage to the amygdala in epilepsy or after status epilepticus suggests that
      local alterations in inhibitory circuitries may contribute to a lowered seizure
      threshold and greater excitability within the amygdala. Furthermore, damage to
      select nuclei in the amygdala may predict impairment of performance in behavioral
      tasks that depend on the integrity of the amygdaloid circuits.

PMID- 9761325
TI  - Antiepileptic effects of allopurinol on EL mice are associated with changes in
      SOD isoenzyme activities.
AB  - We have investigated the potential antiepileptic action of superoxide dismutase
      (SOD) activities in the brain of the epileptic mutant EL mouse. EL mice which
      experienced frequent seizures (EL[s]) had abnormally low levels of SOD isoenzyme
      activity in the hippocampal area. Once epileptogenicity was established in these
      animals, activity of cyanide-sensitive Cu,Zn-SOD was maintained at significantly
      lower levels than in control mice. However, cyanide-insensitive Mn-SOD activity
      was not different from non-epileptic controls. In EL mice which had not
      experienced seizure provoking stimulations and exhibited no seizures (EL[ns])
      there was moderately lower levels of SOD isoenzyme activities compared to
      controls. In spite of the low level of Cu,Zn-SOD activity in EL[s] mice, the
      Cu,Zn-SOD protein content was high in the hippocampus of these animals,
      suggesting that inactive Cu,Zn-SOD might be induced during development. After
      allopurinol (ALP) was given orally to EL[s] mice, Cu,Zn-SOD activities increased
      dramatically in the hippocampus and seizure activity was decreased. Even after 48
      h, when antiepileptic action of ALP was lost, the SOD activity was maintained at
      the high level associated with initial ALP administration. EL[s] mice also showed
      DNA fragmentation in the hippocampal CA1 region and the parietal cortex, detected
      with in situ terminal transferase-mediated dUTP nick labeling with the aid of
      alkaliphosphatase or peroxidase. The degree of DNA fragmentation was less severe
      in EL[ns] mice. We propose that abnormalities in region specific Cu,Zn-SOD
      isoenzyme activity might produce free radicals, leading to DNA fragmentations and
      cell loss. This might contribute to hippocampal epileptogenesis in EL mice.

PMID- 9761326
TI  - Hormonal and gestational parameters in female rats submitted to the pilocarpine
      model of epilepsy.
AB  - Endocrine and reproductive alterations are frequently reported to occur in women
      with temporal lobe epilepsy as well as in female rats in different experimental
      models of limbic seizures. As previously reported, women with epilepsy have lower
      fertility rates than women without epilepsy (Tanganelli, P., Regesta, G., 1992.
      Neurology (suppl.) 42 (5), 89-93; Cummings, L.N., Guidice, L., Morrel, M.J.,
      1995. Epilepsia 36, 355-359). In order to investigate the possible substrate of
      endocrine alterations in epilepsy, hormonal and gestational parameters were
      studied in female rats submitted to the pilocarpine model of epilepsy. The
      results demonstrated that the oestrus cycle is altered following pilocarpine
      induced status epilepticus and such alteration lasted for several weeks.
      Progesterone, LH and FSH levels decreased and estradiol levels increased
      significantly during the period of spontaneous and recurrent seizures. The
      frequency of seizures during pregnancy and lactation decreased. These results
      document that significant changes in gonadal, hypophyseal and hypothalamic
      hormones, as well as in sexual behaviour, occur following status epilepticus
      induced by pilocarpine administration.

PMID- 9761327
TI  - Osmolarity, ionic flux, and changes in brain excitability.
AB  - The majority of modern epilepsy research has focused on possible abnormalities in
      synaptic and intrinsic neuronal properties--as likely epileptogenic mechanisms as
      well as the targets for developing novel antiepileptic treatments. However, many
      other processes in the central nervous system contribute to neuronal excitability
      and synchronization. Regulation of ionic balance is one such set of critical
      processes, involving a complex array of molecules for moving ions into and out of
      brain cells--both neurons and glia. Alterations in extracellular-to-intracellular
      ion gradients can have both direct and indirect effects on neuronal discharge. We
      have found, for example, that when hippocampal slices are exposed to hypo-osmotic
      bathing medium, the cells not only swell, but there is also a significant
      increase in the amplitude of a delayed rectifier potassium current in inhibitory
      interneurons--an effect that may contribute to the increase in tissue
      excitability associated with hypo-osmolar treatments. In contrast, antagonists of
      the chloride co-transporter, furosemide or bumetanide, block epileptiform
      activity in both in vitro and in vivo preparations. This antiepileptic effect is
      presumably due to the drugs' ability to block chloride co-transport. Indeed,
      prolonged tissue exposure to low levels of extracellular chloride have a parallel
      action. These experiments indicate that manipulation of ionic balance may not
      only facilitate epileptiform activities, but may also provide insight into new
      therapeutic strategies to block seizures.

PMID- 9761328
TI  - Properties of human glial cells associated with epileptic seizure foci.
AB  - We studied physiological properties of glial cells from acute slices of biopsies
      from patients operated for intractable mesio-temporal lobe epilepsy using whole
      cell patch-clamp recordings. Cells were filled with Lucifer Yellow (LY) during
      recordings to allow morphological reconstruction and immunohistochemical cell
      identification. Seizure-associated astrocytes had complex, arborized, highly
      branched processes giving them a stellate appearance, and cells stained intensely
      for the intermediate filament GFAP as previously reported for 'reactive'
      astrocytes. GFAP-positive astrocytes from epilepsy biopsies consistently
      expressed voltage-activated, TTX-sensitive Na+ channels that showed fast
      activation and inactivation kinetics. Unlike comparison astrocytes, derived from
      tissues that were not associated with seizure foci, these astrocytes expressed
      Na+ channels at densities sufficient to generate slow action potentials (spikes)
      in current clamp studies. In these cells, the ratio of Na+ to K+ conductance was
      consistently 3-4-fold higher than in comparison human or control rat astrocytes.
      Four of 17 astrocytes from epilepsy patients versus 14/14 from control rat
      hippocampus and four of five in comparison human tissue showed a lack of inwardly
      rectifying K+ currents, which in normal astrocytes are implicated in the control
      of extracellular K+ levels. These results suggest that astrocytes surrounding
      seizure foci differ in morphological and physiological properties, and that glial
      K+ buffering could be impaired at the seizure focus, thus contributing to the
      pathophysiology of seizures.

PMID- 9761329
TI  - Valproate selectively reduces the persistent fraction of Na+ current in
      neocortical neurons.
AB  - The effect of valproate (VPA) on Na+ currents (INa), was studied by means of
      voltage clamp recordings using whole-cell patch clamp configuration in 21 acutely
      dissociated neocortical neurons. Concentrations of VPA up to 200 microM failed to
      induce any detectable decrease in fast INa (I(Naf)), but the persistent fraction
      (I(NaP)) was significantly reduced by low VPA concentrations (10-30 microM),
      corresponding to the lower values of the 'therapeutic' range in epileptic
      patients. Since it is known that I(NaP) critically regulates the firing
      properties of pyramidal neurons, it is suggested that the anticonvulsant
      effectiveness of VPA is mainly due to its effect on I(NaP).

PMID- 9761330
TI  - Effect of valproic acid on sodium currents in cortical neurons from patients with
      pharmaco-resistant temporal lobe epilepsy.
AB  - In a selected group of temporal lobe epilepsy patients with seizures refractory
      to pharmacological treatment, pharmacological seizure control can be attained by
      surgical resection of the epileptic zone. We investigated to what extent pharmaco
      resistance is reflected in a reduced response at the cellular level, in neurons
      acutely isolated from the temporal cortex resected in 20 patients. We studied the
      effect of valproic acid (VPA) on the transient sodium current, measured under
      whole-cell voltage-clamp conditions. We compared neurons from patients with
      temporal lobe sclerosis (S) with neurons from patients without hippocampal
      sclerosis (nS) and compared hippocampal CA1 neurons (CA) with neocortical neurons
      (NC). We could not detect differences in the voltage dependence and kinetics of
      sodium current activation and inactivation in any of the group comparisons. VPA
      shifted the voltage dependence of steady-state inactivation (expressed as V(h,i)
      in a Boltzmann fit) to more hyperpolarized levels. The shift induced by 2 mM VPA
      was -5.1 +/- 0.7 mV in CA-S (n = 13), -5.1 +/- 0.7 mV in CA-nS (n = 25), -4.3 +/-
      0.5 mV in NC-S (n = 17) and -4.9 +/- 0.5 mV in NC-nS (n = 16) The relation
      between concentration and voltage shift had an EC50 of 1.4 +/- 0.2 mM VPA (n =
      16) and a maximal shift of 9.6 +/- 0.9 mV. We conclude that pharmaco-resistance
      in these patients is not associated with a changed modulation of the sodium
      current by VPA. Results are discussed in the light of a reduced sodium current
      modulation by carbamazepine in CA1 neurons of patients with hippocampal sclerosis
      and of similar observations in the kindling model of epileptogenesis.

PMID- 9761331
TI  - Voltage-dependent Ca2+ currents in epilepsy.
AB  - Voltage-dependent Ca2+ channels (VCCs) represent one of the main routes of Ca2+
      entry into neuronal cells. Changes in intracellular Ca2+ dynamics and homeostasis
      can cause long-lasting cellular changes via activation of different Ca2+
      dependent signalling pathways. We have investigated the properties of VCCs in
      human hippocampal dentate granule cells (DGCs) using the whole-cell configuration
      of the patch-clamp method. Classical high-threshold Ca2+ currents were composed
      mainly of omega-CgTx-sensitive N-type and nifedipine-sensitive L-type currents
      that were present in similar proportions. In addition, a Ca2+ current component
      that was sensitive to low concentrations of Ni2+, but not to nifedipine or omega
      conotoxin GVIA (omega-CgTx GVIA) was present. This latter component showed a half
      maximal inactivation at more hyperpolarized potentials than high-threshold
      currents and a more rapid time-dependent inactivation. This current was termed T
      type Ca2+ current. Current components with similar pharmacological and kinetic
      characteristics could be elicited in acutely isolated control rat DGCs. The
      current density of high threshold and T-type Ca2+ components was significantly
      larger in human DGCs and in the kainate model compared to DGCs isolated from
      adult control rats. These differences in current density were not accompanied by
      parallel differences in the voltage-dependence of VCCs. Taken together, these
      data suggest that an up-regulation of Ca2+ current density may occur in
      hippocampal epileptogenesis without consistent changes in Ca2+ current
      properties.

PMID- 9761333
TI  - Effect of nisin on heat injury and inactivation of Salmonella enteritidis PT4.
AB  - The ability of heat injury to confer sensitivity to nisin in a Gram negative
      pathogen was investigated. Injury and inactivation kinetics of Salmonella
      enteritidis PT4 in the presence of nisin were determined in media, liquid whole
      egg and egg white using cultural methods and capacitance monitoring to detect
      injury. Addition of nisin in concentrations from 500 IU/ml to 2500 IU/ml in the
      heating menstruum caused a reduction of required pasteurisation time of up to
      35%, principally as a result of its effect on cells suffering damage during
      heating. In egg white and liquid whole egg the organism's heat susceptibility was
      greater than in nutrient broth, particularly in egg white which contained no fat
      and had an alkaline pH. The effect of nisin on heat susceptibility was however
      less pronounced than in nutrient broth due to its interaction with protein and
      fat. Though nisin did not enhance the lethality of heat processes, injury is more
      severe in egg white containing nisin, presumably as a result of its interaction
      with antimicrobial factors in egg white.

PMID- 9761332
TI  - Type E botulism associated with vacuum-packaged hot-smoked whitefish.
AB  - On January 16, 1997 two Germans got botulism after eating hot-smoked Canadian
      whitefish produced in Finland. The serum sample of one of the patients contained
      6 MLD/ml of botulinum toxin. The type of toxin was identified as E by the toxin
      neutralization test and the botulinum neurotoxin type E (BoNT/E) gene was also
      amplified from the serum by polymerase chain reaction (PCR), but C. botulinum
      could not be isolated from the positive serum sample. The remains of the hot
      smoked whitefish eaten by the patients contained botulinum toxin detected by the
      mouse bioassay and the BoNT/E gene as determined by PCR. C. botulinum was
      isolated from the fish sample and it was confirmed to be type E by the mouse
      bioassay and by PCR. Eleven other fish samples from the same lot did not contain
      botulinum toxin nor any BoNT gene. The incriminated food was processed on the 9th
      and 10th of January, 1997 from frozen whitefish imported to Finland from Canada.
      The pulsed-field gel electrophoretic pattern of the isolated C. botulinum strain
      resembled a reference strain of North American origin. It did not match any C.
      botulinum strains isolated from the Baltic sea-bottom or from the fish caught in
      the area indicating that the fish was contaminated by C. botulinum in Canada. The
      conditions resulting in toxin production could not be identified. The safety
      problems associated with vacuum-packaged hot-smoked fish seem to be of utmost
      concern and the product is one of the most important botulism food vehicles
      processed on an industrial scale. Temperature monitoring and the use of time
      temperature indicators are to be recommended in order to ensure adequate storage
      temperature from processing through to consumption. Allowing the use of nitrate
      and nitrite together with sufficiently high NaC1 concentration in this particular
      product should also be considered.

PMID- 9761334
TI  - Combined effect of nisin and high hydrostatic pressure on destruction of Listeria
      innocua and Escherichia coli in liquid whole egg.
AB  - High hydrostatic pressure inactivation of Escherichia coli and Listeria innocua
      inoculated in liquid whole egg was improved significantly (P < 0.05) with nisin
      addition at concentrations of 1.25 and 5 mg/1. A reduction of almost 5 log10
      units in E. coli counts and more than 6 log10 units for L. innocua was obtained
      at 450 MPa and 5 mg/l of nisin. For this treatment, the two microorganisms were
      not detectable after 1 month of storage at 4 degrees C. The amount of nisin added
      did not affect E. coli inactivation at 300 MPa. For L. innocua, 5 mg/l of nisin
      was more effective than 1.25 mg/l. Nisin showed no effect when samples were
      stored at 20 degrees C after pressurization, except for samples with L. innocua
      containing 5 mg/l of nisin and treated with 450 MPa.

PMID- 9761335
TI  - The combined affects of modified atmosphere, temperature, nisin and ALTA 2341 on
      the growth of Listeria monocytogenes.
AB  - A cocktail of seven Listeria monocytogenes isolates of food, human and
      environmental origin was used to assess the antilisterial activity of the
      bacteriocins nisin and ALTA 2341 in combination with various atmospheres: air,
      100% N2, 40% CO2:60% N2, or 100% CO2. Buffered tryptone soya broth (pH 6.0) was
      used as the growth medium and incubation was at 4 degrees C (21 days) or 12
      degrees C (7 days), or when temperature fluctuated between these values for
      defined periods. It was observed that atmosphere alone influenced the growth rate
      of L. monocytogenes, with 100% CO2 exerting the greatest inhibition. A 5 log
      population increase was observed in all atmospheres after 7 days at 12 degrees C.
      At 4 degrees C a 4-5 log population increase was observed in air, 100% N2 and 40%
      CO2:60% N2 within 21 days. Growth was prevented by 100% CO2. In the presence of
      nisin (400 IU/ml), an increase in the lag phase was observed before growth (5 log
      population increase after 7 days) in all atmospheres at 12 degrees C. This effect
      was enhanced at 4 degrees C where a maximum 2 log population increase was
      observed in all atmospheres except 100% CO2, in which growth was prevented.
      Increasing the concentration of nisin to 1250 IU/ml prevented L. monocytogenes
      growth in all atmosphere combinations at 4 and 12 degrees C. Two concentrations
      of ALTA 2341 were also tested. In the presence of 0.1% ALTA 2341 and at 12
      degrees C, a 3-5 log population increase was observed in all atmospheres with the
      exception of 100% CO2, which prevented L. monocytogenes growth. At 4 degrees C,
      growth was observed in the combination of 0.1% ALTA 2341 and 100% N2 only (3 log
      population increase). Use of a higher concentration of ALTA 2341 (1.0%) resulted
      in a population decrease below the detection level within 24 h in all
      atmosphere/temperature combinations. Re-growth occurred in the presence of 1.0%
      ALTA 2341 in all atmospheres at 12 degrees C, and in combination with air or 100%
      N2 at 4 C. When the effectiveness of either nisin or ALTA 2341 and atmosphere was
      tested against L. monocytogenes as temperature fluctuated for periods between 4
      and 12 degrees C, only the combination of 100% CO2 and 1.0% ALTA 2341 prevented
      growth. Cells surviving exposure to nisin or ALTA 2341 were recovered from 28 of
      the 32 combinations tested that contained bacteriocin. Nisin survivors remained
      sensitive to the bacteriocin. ALTA 2341 survivors had become resistant to the
      bacteriocin.

PMID- 9761336
TI  - The antimicrobial activity of acidocin CH5 in MRS broth and milk with added NaCl,
      NaNO3 and lysozyme.
AB  - The ability of acidocin CH5, a bacteriocin from Lactobacillus acidophilus CH5 in
      the form of neutralized and heated supernatant, to prevent the growth of the
      indicator Lactobacillus delbrueckii subsp. lactis LTI 30 alone or together with
      other antimicrobials was investigated. The inhibitory activity of acidocin CH5
      was higher in MRS broth than in reconstituted skim milk (RSM). In MRS broth and
      RSM, 1.92 and 32 AU acidocin CH5/ml, respectively, caused 97 and 89% inhibition
      of the indicator Lactobacillus delbrueckii subsp. lactis LTI 30. The presence of
      5 and 10% milk fat in RSM decreased the inhibitory activity of acidocin CH5 to 20
      and 11%, respectively. The inhibitory activity of acidocin CH5 was also reduced
      in the presence of NaCl, NaNO3 and lysozyme. In RSM the inhibition was weaker
      with both acidocin CH5 and NaCl added compared with NaCl alone. In MRS broth the
      inhibition was stronger with both acidocin CH5 and NaCl added compared with NaCl
      alone. The inhibition of the indicator Lactobacillus delbrueckii subsp. lactis
      LTI 30 was stronger with both NaNO3 and acidocin CH5 in MRS broth (but not in
      RSM) than with only NaNO3 present, but the strongest level was obtained with
      acidocin CH5 alone. Addition of acidocin CH5 and more than 30 mg/ml lysozyme to
      MRS broth increased the level of inhibition above the level obtained by acidocin
      CH5 alone. The indicator Lactobacillus delbrueckii subsp. lactis LTI 30 was also
      sensitive to NaCl, NaNO3 and lysozyme in both MRS broth and RSM.

PMID- 9761337
TI  - A novel modelling approach for predicting microbial growth in a raw cured meat
      product stored at 3 degrees C and at 12 degrees C in air.
AB  - To predict microbial growth during chill storage of a traditional Greek raw
      sausage, a numerical model was developed and validated. In our novel approach,
      the specific growth rate of each microbial population was calculated on the basis
      of the main microbial populations grown in the sausage. In addition, the specific
      destructive effect of the sausage ecosystem was introduced to evaluate microbial
      growth. The model was integrated by the Runge-Kutta method and the parameter
      values were optimised by the least squares method. Fitting of the model to the
      experimental data derived from four sausage batches stored aerobically at 3 and
      12 degrees C successfully described the microbial growth kinetics in the sausage
      niche. Finally, the parameter values estimated by the fitting of the model on the
      data set from each batch were used to predict microbial growth in the other
      batches at both storage temperatures.

PMID- 9761338
TI  - Molecular characterization of the Lactobacillus community in traditional
      processing of Mozzarella cheese.
AB  - The natural Lactobacillus community involved in traditional Mozzarella cheese
      production has been investigated. The bacterial associations of whey, curd before
      stretching and Mozzarella were analyzed using randomly amplified polymorphic DNA
      (RAPD) to follow growth kinetics, and 16S rDNA sequencing to identify the
      taxonomical position of isolated strains. Analysis of RAPD fingerprints revealed
      that the Lactobacillus community was composed of 13 different biotypes and the
      sequence analysis of 16S rDNA demonstrated that the isolated strains belong to L.
      plantarum, L. fermentum, L. helveticus and L. casei subsp. casei. In addition,
      two strains of Weissella hellenica were isolated on selective media for
      lactobacilli. The four L. casei subsp. casei strains and W. hellenica contained
      sequences related to the prtP gene coding for proteinase, and the highest
      proteolytic activity in milk was found in one strain of L. casei subsp.casei.

PMID- 9761339
TI  - Comparison of five typing methods for the epidemiological study of Listeria
      monocytogenes.
AB  - Five typing methods were compared in a study designed to adapt a strategy for
      epidemiologically typing large numbers of Listeria monocytogenes strains. The
      methods studied were serotyping, electrophoretic typing of esterases
      (zymotyping), restriction fragment length polymorphism of ribosomal DNA
      (ribotyping), random amplified polymorphic DNA (RAPD) and pulsed-field gel
      electrophoresis (PFGE). Data were analysed by computer-assisted statistical
      analysis. Included in the analysis were 35 strains of L. monocytogenes, including
      14 epidemic strains isolated during outbreaks in France in 1992 and 1993, and 21
      strains isolated from food and the environment. Five serotypes, eight zymotypes,
      ten ribotypes, 13 RAPD patterns and 12 PFGE patterns were identified among the 35
      strains. The most discriminating combination of typing methods was ribotyping and
      PFGE typing [27 types, discriminatory index (D.I.) = 0.978]. A factorial analysis
      of correspondence for each method differentiated the epidemic strains from the
      environmental strains. This study shows that computer-assisted statistical
      treatment of the data, combined with the use of discriminating typing methods, is
      a powerful tool for the epidemiological analysis of Listeria monocytogenes.

PMID- 9761340
TI  - Relationship between volatile components of citrus fruit essential oils and
      antimicrobial action on Penicillium digitatum and penicillium italicum.
AB  - This study examined the effect of volatile components of citrus fruit essential
      oils on P. digitatum and P. italicum growth. The hydrodistilled essential oils of
      orange (Citrus sinensis cvv. "Washington navel", "Sanguinello", "Tarocco",
      "Moro", "Valencia late", and "Ovale"), bitter (sour) orange (C. aurantium),
      mandarin (C. deliciosa cv. "Avana"), grapefruit (C. paradisi cvv. "Marsh
      seedless" and "Red Blush"), citrange (C. sinensis x Poncirus trifoliata cvv.
      "Carrizo" and "Troyer"), and lemon (C. limon cv. "Femminello", collected in three
      periods), were characterized by a combination of GC and GC/MS analyses. The
      antifungal efficacy of the oils was then examined at progressively reduced rates.
      Findings showed a positive correlation between monoterpenes other than limonene
      and sesquiterpene content of the oils and the pathogen fungi inhibition. The best
      results were shown by the citrange oils, whose chemical composition is reported
      for the first time, and lemon. Furthermore P. digitatum was found to be more
      sensitive to the inhibitory action of the oils.

PMID- 9761341
TI  - Molecular epidemiology of Salmonella serotype Enteritidis. Relationships between
      food, water and pathogenic strains.
AB  - A molecular epidemiology study of Salmonella serotype Enteritidis was carried out
      by ribotyping performed with a mixture of PstI and SphI (PS ribotyping), and
      randomly amplified polymorphic DNA (RAPD) typing conducted with the OPB17 primer.
      A series, including 38 food and 25 water strains, which were epidemiologically
      unrelated and collected in Spain over 1985-1996, was differentiated into 20 PS
      ribotypes [discrimination index (DI) = 0.67], RAPD types (DI = 0.28), and by
      combining both methods into 23 genomic groups (DI = 0.76). With ribotyping data
      from the strains tested in this and in a previous work, including clinical and
      reference strains, a similarity dendrogram was traced and the subsequent branches
      and groupings were correlated with RAPD types, phage types and sources of origin.
      At a similarity level of 55%, a major cluster (grouping five subclusters and
      three single branches) and two minor clusters were revealed. Results supported
      the fact that organisms representing, at least, 40 genomic groups are currently
      circulating in Spain, but that only the organisms of five groups predominate and
      these fall into a single subcluster or lineage. Organisms of these five groups
      could be considered endemic, associated with food-borne human infections and, for
      epidemiological purposes, can be differentiated by phage typing. The most
      frequent phage types can be subdivided into genomic groups. Organisms of the
      prevalent genomic groups and several less frequent ones were mainly associated
      with poultry transmission and gastroenteritis as the major clinical forms, while
      organisms of another two frequent groups were mainly associated with extra
      intestinal infections, and organisms of four infrequent groups were only
      collected from sewage or environmental waters.

PMID- 9761342
TI  - A collaborative study on media for the enumeration of yeasts in foods.
AB  - A collaborative study was made to evaluate the effectivity of a general purpose
      medium, tryptone glucose yeast extract (TGY) agar on the detection and
      enumeration of yeasts from food. Nine laboratories participated in the study and
      compared five media (four kinds of TGY with different concentrations of glucose,
      one of them without tryptone, and, for comparison, dichloran rose bengal
      chloramphenicol (DRBC) agar). Six food samples were investigated by each
      laboratory and 23 additional food samples were investigated individually by
      different laboratories. No difference was found in the performance of media with
      either the samples common to all laboratories or the various samples tested in
      different ones. A medium consisting of tryptone, glucose and yeast extract, at
      any concentration of glucose tested, appeared reliable for the detection and
      enumeration of yeasts from foods, and its performance did not differ from that of
      DRBC. Omission of tryptone as recommended by ISO provided an even simpler medium
      of equally good performance. TGY without chloramphenicol may result in higher
      total counts due to the development of bacteria. DRBC incubated in light results
      in lower counts compared to that incubated in the dark.

PMID- 9761343
TI  - Relation between the generation time and the lag time of bacterial growth
      kinetics.
AB  - In predictive microbiology, the relation between the lag time (Lag) and the
      generation time (Tg) is commonly assumed to be proportional, as long as the pre
      incubation environmental conditions remain constant. This relation was
      statistically examined in nine published datasets. For every dataset, it was
      roughly proportional. However, a more advanced study showed that the ratio Lag/Tg
      was not totally independent of the environmental conditions. In particular, a
      significant negative effect of the pH on this ratio was observed in five of the
      nine datasets. For modeling the environmental dependence of microbial growth
      parameters, some authors independently deal with Lag and Tg. Other authors only
      model the environmental dependence of Tg, assuming Lag/Tg to be constant. These
      two modeling methods were statistically compared for the nine datasets under
      study. Results differed from one dataset to another. For some, the model
      developed with a constant ratio Lag/Tg sufficed to describe the data, whereas for
      the others, an independent modeling of Lag and Tg was more satisfactory.

PMID- 9761344
TI  - Concentration of carbon dioxide in the water-phase as a parameter to model the
      effect of a modified atmosphere on microorganisms.
AB  - The effect of modified atmosphere packaging can mainly be attributed to the
      bacteriostatic action of CO2. The dissolved CO2 in the water-phase of a food
      product is strongly dependent on several intrinsic and extrinsic parameters and
      will determine the effectiveness of a modified atmosphere packaging
      configuration. The effect of pH, gas/product ratio, initial %CO2 in the gas
      phase, lard content and storage temperature on the amount of dissolved CO2 was
      screened in a preliminary experiment. The initial CO2-concentration in the gas
      phase and the gas/product ratio turned out to be the two major factors
      determining the amount of dissolved CO2. The initial pH also determined
      significantly the final CO2-concentration in the broth. Temperature and lard
      content were shown to have only a minor effect on the amount of dissolved CO2
      compared to the above mentioned parameters. This demonstrates the importance of
      the packaging configuration in the effectiveness of a modified atmosphere. In a
      second step, a model was constructed to predict the amount of dissolved carbon
      dioxide in modified BHI-broth as a function of the gas/product ratio, the initial
      CO2-concentration and the temperature by means of Response Surface Methodology
      (RSM). A second equation was also derived based on Henry's law and was shown to
      be a powerful tool in the quantification of the effect of intrinsic and extrinsic
      parameters on the CO2-solubility in food products. The possibility of the use of
      the concentration of dissolved CO2 in the water-phase as a determinative factor
      for the inhibitory effect of modified atmospheres was examined on Pseudomonas
      fluorescens. Growth curves at 7 degrees C of P. fluorescens in different
      packaging configurations (initial %CO2 and gas/product ratio) resulting in equal
      amounts of dissolved CO2 were compared. P. fluorescens was shown to be similarly
      inhibited by equal amounts of dissolved CO2-concentrations, independent of the
      packaging configuration. This demonstrates the potential of the application of
      the concentration of dissolved CO2 in the water-phase as a parameter to
      characterise a modified atmosphere and its inhibition of certain microorganisms.

PMID- 9761345
TI  - Microbial populations associated with commercially produced South African sorghum
      beer as determined by conventional and Petrifilm plating.
AB  - Microbial populations of 46 commercially produced sorghum beer samples from
      retail outlets in Johannesburg, South Africa, were enumerated and characterized.
      Aerobic plate counts, lactic acid bacteria counts and yeast counts were performed
      by conventional and Petrifilm plating. Conventional methods yielded yeast counts
      of 7.84 log CFU/ml, lactic acid bacteria counts of 6.44 log CFU/ml and aerobic
      plate counts of 5.96 log CFU/ml. In comparison, Petrifilm counts were 7.85 log
      CFU/ml for yeasts, 5.31 log CFU/ml for lactic acid bacteria and 5.34 log CFU/ml
      for aerobic bacteria. Characterization of 419 predominant bacterial isolates from
      Standard One Nutrient Agar, MRS Agar and corresponding Petrifilm plates yielded
      88.0% lactic acid bacteria, 8.4% Bacillus species, 2.9% Micrococcus species and
      0.7% Gram negative bacteria. Composition of predominant lactic acid bacteria
      populations from Standard One Nutrient Agar and both types of Petrifilm plates
      showed marginal differences. Increased proportions of heterofermentative lactic
      acid bacteria were, however, isolated from conventional MRS Agar compared to the
      modified Petrifilm product which represented the equivalent to MRS Agar.

PMID- 9761346
TI  - A novel, selective synthetic acetamide containing culture medium for isolating
      Pseudomonas aeruginosa from milk.
AB  - A selective synthetic medium has been developed both in liquid (Z-broth) and
      solid (Z-agar) forms for selective isolation of Pseudomonas aeruginosa from
      foods. The simple, easy to prepare peptone-free synthetic medium contained
      acetamide that is metabolized to ammonia and acetic acid providing nitrogen and
      carbon supply. The medium contained no inhibitors. Selectivity of the liquid
      medium was tested by inoculation of pure cultures of different bacteria belonging
      to the groups Bacillus, Pseudomonas, Enterobacteriaceae and Staphylococcus. It
      was found that the selectivity of the medium was complete for the examined range
      of bacteria. However, a similar result was obtained when nitrofurantoin broth was
      used. Applicability of the synthetic agar medium was also tested by a nation-wide
      inter-laboratory test using two milk samples containing 10(3)/ml (sample I) and
      10(5)/ml (sample II) Pseudomonas aeruginosa. According to this test, no
      microbiologically relevant differences were found between the results obtained by
      Z-agar and cetrimide-agar a frequently used selective agar in case of sample II.
      However, a relevant and statistically significant difference was found in the
      results of sample I in favour of the Z-agar, that could indicate the presence of
      a low number of bacteria. Concerning repeatability and reproducibility, Z-agar
      proved to be superior to cetrimide agar.

PMID- 9761347
TI  - Bacteriocin production and competitiveness of Lactobacillus plantarum LPCO10 in
      olive juice broth, a culture medium obtained from olives.
AB  - A culture medium, named olive juice broth, which resembles the natural
      environment of Lactobacillus plantarum in the traditional Spanish-style green
      olive fermentation was obtained from green olives. In this medium, the
      bacteriocin-producing L. plantarum LPCO10 strain was able to produce bacteriocin
      throughout the incubation time (15 days). Bacteriocin purification from olive
      juice broth was achieved by a protocol including ammonium sulphate precipitation
      of cell-free, L. plantarum LPCO10 culture supernatants, and cation-exchange,
      hydrophobic-interaction and reversed-phase chromatographies. In a series of mixed
      cultures in olive juice broth, L. plantarum LPCO10 was able to dominate the
      bacteriocin-sensitive L. plantarum 128/2 strain, whereas the non-bacteriocin
      producing, LPCO10 strain derivative, L. plantarum 55-1 strain did not show such
      capability. These results indicated that olive juice broth may be a valuable
      experimental substitute for olive fermentation brine in gaining more knowledge
      about the role of the bacteriocin-producing L. plantarum strains in the control
      of the Spanish-style green olive fermentation.

PMID- 9761348
TI  - Mathematical modeling to predict the bactericidal effect of processed vinegar on
      Escherichia coli O157:H7.
AB  - The combined effects of acetic acid, temperature and sodium chloride on
      Escherichia coli O157:H7 inactivation were examined in processed vinegar. To
      express their effects, quadratic polynomial models were applied. The logarithm
      transformation of sodium chloride concentration provided a better fit of the data
      than the use of a non-transformation value. On the basis of this finding, the
      polynomial models should be distinguished into two types, i.e. the non-sodium
      chloride model and the sodium chloride model, both of which had high R2 values
      (0.988 and 0.978, respectively).

PMID- 9761349
TI  - Impact of recurrent nephrotic syndrome after renal transplantation in young
      patients.
AB  - Recurrent disease is a frequent complication of patients transplanted for steroid
      resistant nephrotic syndrome associated with focal segmental glomerulosclerosis.
      Its long-term prognosis has rarely been studied. We examined 39 patients aged 4
      25 (mean 13.5) years at the time of first transplantation (TX). Twelve of these
      (30%) developed nephrotic syndrome after the first TX and 2 of 8 after the second
      TX. The mean observation period from first TX to last observation with a
      functioning graft or graft loss was 5.4 (0.1-19.3) years. We confirmed that
      recurrent disease is associated with older age at onset of the primary disease,
      shorter time from onset to end-stage renal disease, and diffuse mesangial
      proliferation in the initial kidney biopsy. Remissions occurred in all 3 children
      undergoing early repeated plasma exchange and in 1 adolescent following
      introduction of cyclosporin A 7 years after TX. At last observation 42% of
      relapsing and 48% of non-relapsing patients with a similar follow-up period had a
      functioning first graft. Median first graft survival was almost identical in the
      relapsing and the non-relapsing patients (4.3 vs. 4.2 years). Histological
      lesions of focal glomerulosclerosis were detected in the posttransplant biopsies
      of only 3 patients. In conclusion, young patients with nephrotic syndrome
      associated with focal segmental sclerosis have a similar graft survival with and
      without recurrence of the nephrotic syndrome.

PMID- 9761350
TI  - Comparable renal graft survival in African-American and Caucasian recipients.
AB  - In past years, many pediatric transplant centers found African-American renal
      transplant recipients to have poor graft survival. Since 1991 anti-lymphocyte
      induction therapy has been routinely used for pediatric cadaveric (CAD) and
      living-related donor (LRD) renal allograft recipients at the University of
      Tennessee, Memphis. Sixteen African-American first renal allograft recipients
      received induction therapy: 11 CAD allografts (10 OKT3, 1 ATGAM) and five LRD
      (all ATGAM). Sixteen Caucasian recipients received induction therapy; 3 CAD (all
      OKT3), 1 living-unrelated donor (OKT3), and 12 LRD (9 ATGAM, 3 OKT3). Mean age at
      renal transplantation was 11.8 and 10.5 years for African-American and Caucasian
      recipients, respectively. Predicted graft survival (PGS) estimated by the Kaplan
      Meier method for the African-American patients was 94% at both 1 and 3 years, and
      for Caucasian patients was 94% and 85% at 1 and 3 years, respectively. Eleven
      African-American CAD recipients had a PGS of 91% at 1 and 3 years. Renal
      allograft survival for African-American and Caucasian pediatric recipients at our
      center appears to be comparable. This could be due, in part, to the use of anti
      lymphocyte induction therapy. However, other factors, such as improved compliance
      or better immunological and pharmacological monitoring, may also have
      contributed.

PMID- 9761351
TI  - The ontogeny of the expression of K+ channel-like gene (CHIF) in the rat kidney
      papilla.
AB  - Recently, an IsK-like potassium (K+) channel corticosteroid-induced gene (CHIF)
      was cloned. A high-K+ diet enhances, while a low-K+ diet decreases the expression
      of this gene. The major expression of CHIF in the adult rat kidney is in the
      papilla, where it is constitutive, in contrast to its inducibility by
      corticosteroids and a low-salt diet in the rat colon. In order to further
      understand the ontogeny of K+ clearance, we studied the presence of CHIF in the
      kidney papilla in different stages of rat development. Total RNA from rat kidney
      papillae of 1- to 3-day pre-labor unborn offspring, 2- to 3-day-old newborns, 10
      day-old, 6-week-old, and 43-week-old rats underwent northern hybridization for
      CHIF and the alpha-subunit of the Na+-K+-ATPase mRNA. Minor expression of CHIF
      mRNA was found in fetal and newborn rat papillae, while older rats showed an age
      related increase in gene expression. The expression of the alpha-sub unit of the
      Na+-K+-ATPase was not age related. We conclude that CHIF is present in the rat
      kidney papilla and the expression is related to age. The relative deficiency of
      CHIF in the newborn may be one of the factors responsible for the reduced K+
      clearance in is period.

PMID- 9761352
TI  - Ovine AQP1: cDNA cloning, ontogeny, and control of renal gene expression.
AB  - The cDNA for the ovine aquaporin 1 (AQP1) was obtained and found to be 97%, 88%,
      and 85%, respectively, homologous to the bovine, human, and rat AQP1 cDNA. The
      level of total kidney mRNA expressed as a ratio to glyceraldehyde-3-phosphate
      dehydrogenase increased sevenfold from 60 days to 140 days of gestation (term=150
      days) and reached adult values by 6 weeks after birth. Treatment of pregnant ewes
      (and their fetuses) at 64 and 74 days of gestation with dexamethasone (0.76 mg/h
      for 48 h) resulted in a small but statistically significant increase in AQP1 mRNA
      only in the 74-day fetuses. By immunohistochemistry, it was shown that the
      increase in AQP1 mRNA with dexamethasone resulted largely from an increase in
      maturity of the inner zone of the fetal renal cortex (i.e., more tubules) as well
      as stronger expression of AQP1 in proximal tubules and thin descending limbs of
      loops of Henle. A similar effect occurred in fetuses infused for 3 days with
      angiotensin I (6.7 microg/h) in the last third of gestation.

PMID- 9761353
TI  - Expression of type IV collagen in the developing human kidney.
AB  - The distribution of alpha1-6 chains of type IV collagen (alpha1-6(IV)) in human
      fetal kidneys was examined by indirect immunofluorescence. By 11 weeks of
      gestation, alpha1, 2, 3, 4, and 6(IV) were already present, but alpha5(IV)
      appeared relatively late, at 21 weeks. Alpha1(IV) and alpha2(IV) were present in
      all basement membranes, alpha3(IV) and alpha4(IV) were restricted to the
      glomerular basement membrane and parts of the tubular basement membrane.
      Alpha5(IV) was distributed in the glomerular basement membrane, Bowman's capsule,
      and parts of the tubular basement membrane. Alpha6(IV) was present in the
      Bowman's capsule, parts of the tubular basement membrane, and occurred in parts
      of the glomerular basement membrane at the early capillary loop stage, but
      disappeared during the later capillary loop stage.

PMID- 9761354
TI  - Early sonographic aspects of kidney morphology in Bardet-Biedl syndrome.
AB  - Bardet-Biedl syndrome is an autosomal recessive disorder characterized by
      postaxial hexadactyly, obesity, mental retardation, pigmented retinopathy,
      hypogonadism, and renal disease. Morphological changes are present in all areas
      of the kidney, the renal medulla being the most frequently affected site. Cystic
      and dysplastic changes are prevalent. Seven children from five families were
      followed from birth through their 5th birthday. Serial renal sonography revealed
      a number of characteristic features. Bilateral renal enlargement and increased
      parenchymal echogenicity were present at birth. The usual corticomedullary
      differentiation was absent. Pyramids were either not seen or deformed. With high
      resolution ultrasonography, small cysts were detected at the corticomedullary
      junction. After the 3rd month of life, there was a striking inversion of normal
      echogenicity, the inner medulla became more echogenic and was demarcated from the
      less-echogenic cortex. After 12 months, the kidney size regressed significantly.
      Fetal lobulation persisted in some patients. In conclusion, ultrasonography is a
      useful tool to evaluate the extent of renal lesions, but more importantly to
      differentiate bilateral polycystic kidney diseases in the newborn period.

PMID- 9761355
TI  - Benign methylmalonic acidemia in a sibship with distal renal tubular acidosis.
AB  - Two male infants born to consanguineous parents were investigated for feeding
      difficulties in the 1st month of life. Both were found to have distal renal
      tubular acidosis (dRTA) with hypercalciuria. Nephrocalcinosis was present in the
      first child but not in the second. Urinary organic acid profile demonstrated an
      excess of methylmalonic acid (MMA) in both children in the absence of any other
      organic acid. MMA mutase activity and propionate incorporation were normal. There
      have been no neurological symptoms in either child. The first child has normal
      growth and psychomotor development at 4 years. His brother, who also has
      significant gastrooesophageal reflux, has failed to thrive and currently requires
      nasogastric feeding and caloric supplements to maintain weight along the 3rd
      percentile. Urinary and plasma MMA continue to be raised in both cases. The
      association of increased urinary and plasma MMA and dRTA presenting in the 1st
      month of life has not previously been reported and may represent a new syndrome
      of autosomal recessive inheritance.

PMID- 9761356
TI  - Kidney growth and renal function in unilateral multicystic dysplastic kidney
      disease.
AB  - The natural history of multicystic dysplastic kidney (MCDK) is not well
      established. We analyzed kidney growth and renal function in 33 children with
      prenatally diagnosed unilateral MCDK in a long-term study. The mean observation
      period was 4.9 years with a range of 1-11.6 years. Abnormalities of the
      contralateral kidney were found in 10 of 33 patients (30%): ureteropelvic
      junction obstruction (5), ureterovesical junction obstruction (2), and
      vesicoureteral reflux (3). In 6 children the dysplastic kidney had been removed.
      Complete involution was observed in 48% and a decrease of size in 33% of 27
      dysplastic kidneys. At the time of last examination, 27 of 29 children showed a
      volume of the contralateral kidney above the normal range (>145%). Hypertrophy of
      the contralateral kidney, defined as kidney length above 2 standard deviation
      scores (SDS), was seen in 24% of 33 children at birth, thus showing that
      hypertrophy of the contralateral kidney starts in utero and continues throughout
      childhood. The extent of contralateral hypertrophy was independent of associated
      abnormalities in this study. Mean creatinine was increased in the whole group
      (mean +1.13 SDS). Calculated creatinine clearance in 21 patients over 2 years was
      within normal limits, with a median of 102 ml/min per 1.73 m2 (range 84-143).
      Based on the results of this and previous studies, nephrectomy cannot be
      recommended in typical cases, but a regular follow-up of these patients seems
      necessary.

PMID- 9761357
TI  - Long-term nephrotoxicity of cisplatin, ifosfamide, and methotrexate in
      osteosarcoma.
AB  - The acute renal effects of chemotherapy are known, but long-term nephrotoxicity
      has rarely been investigated. The aim of the present study was to assess long
      term renal function in children and adolescents who received at-risk
      chemotherapy, including cisplatin, ifosfamide, and methotrexate, to treat an
      osteosarcoma. Renal function tests [creatinine clearance, microalbuminuria, and
      renal excretion of sodium, potassium, chloride, calcium, magnesium (Mg),
      phosphorus (P), and uric acid] were prospectively performed 5.4+/-2.2 (+/-SD)
      years after chemotherapy (total cumulative dose: methotrexate 41+/-31 g/m2,
      ifosfamide 39+/-14 g/m2, cisplatin 674+/-188 mg/m2) in 18 children and
      adolescents. The results were compared with 13 normal volunteers matched for age
      and sex. Creatinine clearance, which was greater than 80 ml/min per 1.73 m2 in
      all patients, correlated with the total dose of ifosfamide (r=0.55, P<0.05) and
      cisplatin (r=0.48, P<0.05). Microalbuminuria was noted in 4 patients.
      Hypomagnesemia was present in 4 and hypercalciuria in 3 patients; renal excretion
      of P, Mg, and uric acid was higher in patients than in controls. Glomerular
      function was not significantly altered and only mild tubular dysfunction was
      present. Since renal excretion of P and Mg were increased in patients compared
      with normal volunteers and hypercalciuria was occasionally seen, divalent ion
      disorders are the most-likely potential complications.

PMID- 9761358
TI  - Acute interstitial nephritis presenting as presumed minimal change nephrotic
      syndrome.
AB  - Nephrotic syndrome (NS) secondary to drug-induced acute interstitial nephritis
      (AIN) is well described in adult but is very rare in children. We report an
      unusual case of AIN mimicking prototypical childhood minimal change NS. A 2-year
      old girl on long-standing amoxicillin therapy for vesicoureteral reflux presented
      with the acute onset of generalized edema, proteinuria, hypoalbuminemia,
      hypercholesterolemia, and an inactive urinary sediment. She was placed on empiric
      steroid therapy for presumed minimal change NS. When she did not respond to
      steroids, a renal biopsy was performed and revealed AIN. Her NS resolved
      completely with cessation of her amoxicillin therapy and concomitant tapering of
      her steroids. This patient demonstrates that the association of AIN with NS
      should be carefully considered in children on antimicrobials who develop NS, even
      in the absence of the classic clinical features of AIN. In addition to the usual
      work-up and care of a child with NS, in these patients consideration may also
      need to be given to withdrawal of the potential precipitating agent.

PMID- 9761359
TI  - Magnetic resonance imaging in acute pyelonephritis.
AB  - The diagnosis of acute pyelonephritis in children remains a clinical challenge.
      We assessed the feasibility of magnetic resonance imaging (MRI) detection of
      pyelonephritis in four pediatric patients and compared the results with renal
      cortical scintigraphy. MRI revealed areas of high signal intensity in the kidney
      that coincided with photon-deficient regions in the radionuclide scans in two
      children with acute pyelonephritis. These findings confirm work in experimental
      animals and indicate that MRI can accurately detect acute pyelonephritis in
      children.

PMID- 9761360
TI  - Peritoneal loss of insulin-like growth factor-I and binding proteins in end-stage
      renal disease.
AB  - The kinetics of peritoneal transport of insulin-like growth factor (IGF) system
      related proteins during dialysis is not well characterized. We studied temporal
      changes in dialysate and serum concentrations of IGF-I and IGF-II as well as IGF
      binding protein (BP)-1, -2, and -3 in ten children with end-stage renal disease
      (ESRD) undergoing continuous cycling peritoneal dialysis (CCPD) during a 4-h
      peritoneal equilibration test (PET). Dialysate concentrations of IGF-I, IGF-II,
      and all three IGFBPs demonstrated a time-dependent increase during PET. Despite
      their transport, the serum concentrations of these proteins did not change
      significantly during the PET. Dialysate/serum ratios for IGF-I, IGF-II, and IGFBP
      1, -2, and -3 were significantly increased at 2 h and increased further at 4 h,
      at which time values averaged 1.3+/-0.2%, 3.1+/-0.5%, 6.2+/-1.0%, 2.4+/-0.2%, and
      1.3+/-0.2% of serum levels, respectively. The transperitoneal clearance
      (microl/min per 1.73 m2) of the three IGFBPs was inversely related to both their
      molecular weight and plasma concentration. However, peritoneal clearance of IGF-I
      and -II was similar to that of the larger and more-abundant IGFBP-3. Mass
      transfer rates (microg/h per 1.73 m2) for the IGFs and their binding proteins
      were directly proportional to their prevailing plasma concentration. Based on
      estimates of mass transfer, only a small molar excess of IGFBPs was removed from
      the circulation relative to the combined molar concentration of IGF-I and IGF-II.
      Hence, it seems unlikely that any beneficial effect of CCPD on growth in children
      with ESRD is mediated via a preferential loss of IGFBPs into the dialysate fluid.

PMID- 9761361
TI  - Ammonia clearance by peritoneal dialysis and continuous arteriovenous
      hemodiafiltration.
AB  - We report the use of continuous arteriovenous hemodiafiltration (CAVHD) in a
      neonate with severe hyperammonemia due to a urea cycle disorder. We compared the
      ammonia clearance (C(NH3)) for peritoneal dialysis (PD) and CAVHD. C(NH3) for
      CAVHD was 7.45 ml/min per m2 at a dialysate flow of 300 ml/h and was 10.55 ml/min
      per m2 at a dialysate flow rate of 600 ml/h. The mean PD clearance was 2.15
      ml/min per m2. Our data suggest that CAVHD is superior to PD for the removal of
      plasma ammonia. We conclude that CAVHD should be considered a reasonable
      alternative in the treatment of neonatal hyperammonemia in urea cycle disorders
      when medical treatment fails.

PMID- 9761362
TI  - Hemodialysis catheter placement and recirculation in treatment of hyperammonemia.
AB  - A 2-year-old girl with carbamoyl phosphate synthetase deficiency underwent
      emergency hemodialysis (HD) for treatment of acute life-threatening
      hyperammonemia. HD was performed via catheters placed in each femoral vein
      serving as vascular access. The tip of one of the catheters (aspirating line) was
      in the left external iliac vein and the tip of the other catheter (the return
      line) was in the inferior vena cava (IVC). High blood flow rates were used in
      order to rapidly lower the blood ammonia (NH3) levels. However, unanticipated
      marked recirculation in the IVC, between the dialysis aspirating and return
      catheters, was encountered, preventing significant reduction in blood NH3. The
      recognition of this problem, suggested solutions, and prevention are described.

PMID- 9761363
TI  - Regulation of cell survival during renal development.
AB  - Apoptosis occurs in an orchestrated fashion during kidney development. In
      contrast, it is a relatively rare event in normal developed (adult) kidney.
      However, a predictable pattern of apoptosis is observed in adult kidney in two
      settings, during which parts of the developmental pattern are recapitulated.
      These are regeneration following acute ischemic injury and the process of
      cystogenesis in polycystic kidney disease. Apoptosis in kidney is regulated by
      agents both intrinsic and extrinsic to the renal cell. The protooncogene b-cell
      lymphoma/leukemia gene product-2 (bcl-2) is an important intrinsic factor. The
      growth factor epidermal growth factor is an important extrinsic regulator. A
      thorough understanding of the control of renal apoptosis during development and
      recovery from ischemic injury and in cystogenesis may lead to new therapies to
      prevent or ameliorate abnormalities of kidney formation, to enhance regeneration
      following acute ischemic injury, and to slow the progression of renal failure in
      polycystic kidney disease.

PMID- 9761364
TI  - The clinical pharmacology of loop diuretics in the pediatric patient.
AB  - The loop diuretics furosemide and bumetanide are frequently employed in the
      pediatric population for the management of fluid overload in both acute and
      chronic disease states. They act mainly by inhibiting sodium reabsorption in the
      nephron at the thick ascending limb of Henle's loop. Important pharmacokinetic
      differences between adults and infants include a reduced clearance and prolonged
      half-life, that may cause accumulation of these agents to potentially toxic
      levels if dosing intervals are not adjusted. Unfortunately, little is known about
      the time required for maturation of loop diuretic elimination in older infants,
      children, and adolescents. Similar to adults, limited pharmacodynamic evidence in
      neonates suggests that a maximally efficient diuretic dose exists. Increasing the
      diuretic dose beyond this maximum does not offer further benefit, but may
      increase the risk of toxicity. Common problems encountered in the pediatric
      patient as well as in adults are loop diuretic tolerance and resistance. Loop
      diuretic dosing strategies aimed at overcoming these phenomena include
      administration by continuous infusion, coadministration with albumin, and
      coadministration with metolazone or thiazides. This article reviews the
      pharmacology, pharmacokinetics, and pharmacodynamics of furosemide and bumetanide
      in pediatric patients. A better understanding of the clinical pharmacology of the
      loop diuretics should aid clinicians in the development of dosing regimens aimed
      at producing adequate diuresis without promoting excessive diuretic tolerance.

PMID- 9761365
TI  - Prothrombin fragment 1+2 during oral anticoagulation in congenital nephrotic
      syndrome.

PMID- 9761366
TI  - Transferrin saturation in pediatric hemodialysis.

PMID- 9761367
TI  - Signal transduction in leucocytes via GPI-anchored proteins: an experimental
      artefact or an aspect of immunoreceptor function?
AB  - Membrane proteins anchored in the membrane via a glycolipid
      glycosylphosphatidylinositol (GPI) as well as some glycolipids are able to
      transduce signals and induce diverse functional responses in cells upon their
      cross-linking via antibodies or natural ligands. In some cases this signaling
      capacity seems to be due to associations of these molecules with specific
      transmembrane proteins. GPI-anchored proteins are components of membrane
      microdomains enriched in glycosphingolipids and cholesterol and devoid of most
      transmembrane proteins. These membrane specializations are relatively resistant
      to solubilization in solutions of some mild detergents at low temperatures. These
      'GPI-microdomains' contain also cytoplasmic signaling molecules such as Src
      family protein tyrosine kinases and trimeric G-proteins. Thus, at least some
      signaling elicited upon cross-linking of GPI-anchored proteins and glycolipids
      may be due to perturbation of the signaling molecules associated with these
      microdomains. It is suggested that these specialized areas of the membrane rich
      in signaling molecules interact with immunoreceptors (TCR, BCR, Fc receptors)
      cross-linked upon their interactions with ligands and importantly contribute to
      initiation of proximal phases of their signaling pathways.

PMID- 9761369
TI  - A caspase inhibitor protects thymocytes from diverse signal-mediated apoptosis
      but not from clonal deletion in fetal thymus organ culture.
AB  - A family of caspases has been implicated as an effector in various forms of
      apoptosis. The present study investigated whether this family of proteases is
      involved in the induction of intrathymic clonal deletion in comparison with
      apoptosis induced in the thymus by various signals. Potent apoptosis of
      thymocytes was induced in fetal thymus organ cultures (FTOC) when FTOC were
      treated with glucocorticoid, radiation, and anti-CD3 monoclonal antibody (mAb).
      As a model of negative selection based on apoptotic clonal deletion, the
      elimination of Vbeta8-expressing thymocytes was induced by inoculating
      Staphylococcal enterotoxin B (SEB) into FTOC. Addition of a peptide-based caspase
      inhibitor resulted in the protection of thymocytes from apoptosis induced by
      glucocorticoid, radiation, and anti-CD3 mAb. In contrast, the same treatment
      failed to prevent clonal deletion of Vbeta8high thymocytes. These results suggest
      that different pathways of cell death operate in the thymus that may be
      distinguished depending on the caspase/protease utilized in each pathway.

PMID- 9761368
TI  - Establishment and characterization of pro-B cell lines from motheaten mutant
      mouse defective in SHP-1 protein tyrosine phosphatase.
AB  - Mice homozygous for the motheaten (Hcph(me)) mutation lack a functional SHP-1
      protein tyrosine phosphatase, show severe immunologic dysregulation and die at an
      early age. Severe pneumonitis in me/me mice is associated with abnormal
      proliferation of macrophages and granulocytes. Overgrowth of macrophages in long
      term cultures of me/me bone marrow has prevented analyses of lymphopoiesis in
      vitro. To establish hematopoietic cell lines from me/me mice, we cultured me/me
      bone marrow with the PA6 stromal cell line in the presence of antagonistic
      antibody against the receptor (c-Fms) for macrophage colony stimulating factor (M
      CSF). In these cultures, overgrowth of M-CSF-dependent macrophages was suppressed
      by the antagonistic antibody and other hemopoietic cell lineages were generated
      efficiently from me/me bone marrow. By using this culture system, we established
      me/me pro-B cell clones (MEBs) with rearranged DH-JH but not VH-DJH. The growth
      of MEB clones required IL-7 and c-Kit ligand, corresponding to normal pro-B cells
      which express SHP-1. MEB cells were sensitive to starvation by either IL-7 or c
      Kit ligand, resulting in apoptotic death. The present culture system, which
      supports hematopoiesis of me/me bone marrow, provides useful tools for the
      determination of the role of SHP-1 in signal transduction of B lymphopoiesis.

PMID- 9761370
TI  - Donor-specific stimulation of peripheral blood mononuclear cells from recipients
      of orthotopic liver transplants is associated, in the absence of rejection, with
      type-2 cytokine production.
AB  - In this study, we examined the cytokine production by human peripheral blood
      mononuclear cells (PBM) from recipients of orthotopic liver transplants which had
      been stimulated by donor-specific alloantigen. Levels of interleukin (IL)-2, IL
      4, interferon (IFN)-gamma, IL-10 and transforming growth factor (TGF)-beta
      produced in vitro from PBM of 15 transplant recipients at 5-7 months post
      transplantation were analysed after donor-specific, third-party, or non-specific
      stimulation. Mononuclear cell proliferation in response to stimulation and
      cytokine mRNA from the cell cultures were assayed. Donor-specific antigen was
      obtained from donor spleen cells which had been obtained and frozen in liquid
      nitrogen at the time of organ retrieval. Third-party restimulation used
      equivalent numbers of spleen cells pooled from the other 14 organ donors.
      Cytokine production was correlated with the clinical condition of the patient,
      including biopsy results when available, and biochemical data. The data show a
      highly significant correlation between the donor-specific- and third-party-
      stimulated IL-4 and IL-10 production from recipient PBM with stable liver graft
      function as assessed by histopathology and/or biochemistry. This correlation was
      independent of level of immunosuppression. These data strongly support a role for
      IL-4 and/or IL-10 in the induction and/or maintenance of tolerance to human liver
      allografts. Measurement of the levels of these cytokines from recipient PBM after
      donor-specific antigen stimulation in vitro may be a useful test for monitoring
      for acute allograft rejection.

PMID- 9761372
TI  - Different effect of 1,25-dihydroxyvitamin D3 on replication of Mycobacterium
      avium in monocyte-derived macrophages from human immunodeficiency virus-infected
      subjects and healthy controls.
AB  - Mycobacterium avium complex (MAC) is the most common cause of disseminated
      bacterial infection in patients with acquired immune deficiency syndrome (AIDS)
      and macrophage dysfunction is important both in the pathogenesis of AIDS- and MAC
      infection. 1,25-Dihydroxyvitamin D3 (1,25D), the active metabolite of vitamin D,
      has a number of effects on cell types of the immune system including
      monocytes/macrophages. The present study was designed to investigate whether
      1,25D supplementation in vitro could modulate MAC replication in macrophages from
      HIV-infected patients. It was therefore of particular interest to examine whether
      the effect of 1,25D differs between cells from HIV-infected patients and healthy
      control subjects. After 3 and 7 days of infection, 1,25D supplementation
      increased numbers of bacteria in cells from control subjects. In contrast, there
      was no change or even a decrease in numbers of bacteria in cells from HIV
      infected patients. These findings suggest that HIV infection may significantly
      modulate the macrophage response to 1,25D stimulation, and that 1,25D may have
      inhibitory effects on MAC replication in macrophages from HIV-infected patients.

PMID- 9761371
TI  - Activation of CD4+ and CD8+ parasite -specific T-cells by macrophages infected
      with live T. cruzi amastigotes.
AB  - T. cruzi-infected macrophages are potential candidates for the presentation of
      parasite antigens to T. cruzi-specific T lymphocytes. To assess this question, we
      examine the ability of peritoneal exudate macrophages to process exogenous live
      or dead parasites and to activate defined populations of T. cruzi-specific immune
      T-cells. Macrophages infected with live amastigotes activated both lymph node
      CD4+ and spleen CD8 + T-primed cells that proliferated and secreted cytokines.
      Lymph node CD4+ T-cells produced IFN-gamma and IL-10 while CD8 + T-cells produced
      IFN-gamma. In contrast, macrophages pulsed with dead parasites activated only
      lymph node CD4+ T-cells, which proliferated and secreted IFN-gamma.
      Interestingly, the immunization with heat-killed parasites primed mice for CD8+ T
      cells which were expanded in vitro by recognition of infected macrophages. Taken
      together, these results demonstrated that amastigote infected macrophages present
      parasite peptides associated with MHC I and II molecules, activating both CD4 +
      and CD8+ T-cells. Furthermore, the development of T. cruzi-specific CD8+ T-cells
      in vivo using the immunization protocol with non-living parasites as described in
      this report could be explored for further studies on the role of CTL in the
      outcome of infection.

PMID- 9761373
TI  - Nitric oxide-induced apoptotic cell death in the acute phase of Trypanosoma cruzi
      infection in mice.
AB  - Production of gamma-interferon (IFN-gamma) and tumor necrosis factor-alpha (TNF
      alpha) in Trypanosoma cruzi-infected mice results in the activation of inducible
      nitric oxide synthase (iNOS) and in elevated nitric oxide (NO) synthesis, which
      is important for the macrophage trypanocidal activity. However, NO has been shown
      to be involved in suppression of host immunity. In the present investigation, we
      studied the role of NO in inducing apoptosis in cells from BALB/c mice acutely
      infected by T. cruzi. Splenocytes from infected mice had a reduced cell viability
      and elevated levels of spontaneous apoptosis after 48 h in culture. Inhibition of
      NO production by the addition of the L-arginine analog NG-monomethyl-L-arginine
      (L-NMMA), or of monoclonal antibodies (mAbs) to IFN-gamma or TNF-alpha spleen
      cells, partially restored cell viability and caused a decrease in the levels of
      apoptosis in splenocytes from infected animals. Spleen cells from T. cruzi
      infected mice had an apoptosis-specific pattern of internucleosomal DNA
      fragmentation which was most marked at the ninth day after infection when the
      plasma NO levels and parasitemia were increased. Treatment of infected mice with
      L-NMMA, anti-TNF-alpha, or anti-IFN-gamma mAbs caused reduction of both NO
      production and the amount of apoptotic cells, suggesting that NO plays a direct
      role in the induction of apoptosis in vivo. Taken together, these data support
      the hypothesis that, as well as modulating immunosuppression, NO produced by IFN
      gamma and TNF-alpha activated macrophages plays a role in apoptosis induction
      during the acute phase of experimental T. cruzi infection.

PMID- 9761374
TI  - Natural killer cell mediated cytotoxicity against VERO target cells; the
      suppressive effect of pentoxifylline.
AB  - The K-562 cell line is widely known and used as a NK cell target. In this study
      we report that VERO (African green monkey kidney epithelial cell line) is an
      excellent target of the human NK cell cytotoxicity. Considerable cytotoxicity was
      observed in a 4 h 51Cr release assay with nonadherent and immunomagnetically
      separated CD56+ NK cells from PBMC. On the contrary, adding K-562 cells as cold
      target to the assay the cytotoxicity significantly decreased. Using a standard
      chromium-release assay the NK cell activity (NKCA) against VERO cells was
      investigated in a population of healthy volunteers (mean value of cytotoxicity
      was 26.6%) and compared with the values of cytotoxicity against K-562 target
      cells (32.6%). The difference was not significant (P > 0.05). The suppressive
      effect of PTX on in vitro NK cell activity was observed at concentration of 100
      microg/ml using VERO target cells as well as K-562 cells. Our studies provide the
      first evidence that the NK cell activity is suppressed in vitro by PTX using VERO
      cells as NK target cells.

PMID- 9761375
TI  - Long term safety and efficacy of intraperitoneal insulin infusion by means of
      implantable pumps.

PMID- 9761376
TI  - Testosterone and progesterone level alterations in the adult rat after retinoid
      (retinol or retinoic acid) treatment (imprinting) in neonatal or adolescent age.
AB  - Newborn rats were treated with a single dose of vitamin A (retinol), or with
      three doses of retinoic acid (in the 1st, 3rd and 5th days). Serum testosterone
      and progesterone level was measured in the four months old male and female rats,
      respectively. Retinol significantly decreased both hormone levels, however
      retinoic acid decreased the progesterone level only. In the second part of the
      experiments adolescent rats (in the 6th and 7th week after birth) were treated
      and measured similar to the newborns. In this case retinol significantly
      diminished testosterone level, without influencing the progesterone level.
      Retinoic acid decreased testosterone level and elevated progesterone level. The
      results demonstrate the long lasting effects of retinoid treatments at a neonatal
      or adolescent age, pointing also to the differences in the direction of the
      effects. Considering that previously the receptorial and sexual-behavioral
      effects of perinatal vitamin A treatments were observed, the experiments call
      attention to such harmful influences of perinatal vitamin A treatments, which are
      not manifested in morphological alterations.

PMID- 9761377
TI  - Gene expression and roles of angiotensin II type 1 and type 2 receptors in human
      adrenals.
AB  - Although stimulation of aldosterone secretion is one of the functions of
      angiotensin II, the gene expression and biological significance of the
      angiotensin II receptor subtypes, AT1 and AT2, in the human adrenal have not been
      characterized. We therefore investigated the transcription levels of the receptor
      subtype genes and their roles in regulation of steroid secretion by human
      adrenals. The expression of AT1 and AT2 receptor mRNA was assessed by reverse
      transcription-polymerase chain reaction followed by Southern blot analysis in
      normal adrenocortical tissues (n = 6) and a series of adrenal tumour tissues:
      aldosterone-producing adrenocortical adenoma (n=6), Cushing's syndrome (n = 6)
      and pheochromocytoma (n = 6). The role of the two receptor subtypes in steroid
      secretion in vitro was examined by incubating the tissue with angiotensin II(1
      microM) with or without the selective AT1 antagonist CV-11974 (1 microM). Both
      AT1 and AT2 receptor mRNA transcripts were demonstrated in all of the human
      adrenal tissues tested. Angiotensin II-induced aldosterone secretion was
      suppressed 50% upon the addition of CV-11974. The selective AT2 agonist CGP-42112
      increased aldosterone secretion by 55% over the control, which was not suppressed
      by CV-11974. Angiotensin II and CGP-42112 did not affect cortisol secretion.
      These results suggest that both AT2 and AT1 receptors may be involved in the
      regulation of aldosterone secretion and tumorigenesis of the human adrenals.

PMID- 9761378
TI  - Inhibitory effect of pentoxifylline on HLA-DR expression and glycosaminoglycan
      synthesis by retrobulbar fibroblasts.
AB  - OBJECTIVE: Glycosaminoglycan (GAG) production by retro-ocular fibroblasts (REF)
      is increased in patients with thyroid-associated ophthalmopathy (TAO). Various
      cytokines stimulate REFs to proliferate and elaborate GAG, free oxygen radicals
      as well as induce HLA-DR expression on these cells. Pentoxifyllin (Ptx) regulates
      the production of several cytokines including tumor necrosis factor alpha (TNF
      alpha), interleukin-1 (IL-1) and, interferon gamma (IFN-gamma). We wished in this
      study to determine whether Ptx modified the spontaneous and cytokine-induced GAG
      synthesis by REF and IFN-gamma induced HLA-DR expression. DESIGN: REF derived
      from extraocular muscles of healthy subjects were cultured without and with
      cytokines (IFN-gamma, TNF alpha and IL-1) and the effect of Ptx on the production
      of GAG by REF and HLA-DR expression was determined. MEASUREMENTS:
      Glycosaminoglycan was measured by incorporation of (3H) glycosamine into GAG. HLA
      DR expression was analyzed by fluorescence activated cell sorter. RESULTS: Both
      spontaneous and cytokine induced GAG synthesis by REF was inhibited by Ptx (100,
      500 and 1000 mg/l, respectively). IFN-gamma (50, 100 and 500 U/ml) induced a dose
      dependent increase in the expression of HLA-DR molecules by REF. Ptx, which was
      not toxic to REF, inhibited HLA-DR expression on those cells dose-dependently.
      CONCLUSIONS: Our in vitro results suggest that Ptx reduces cytokine-induced GAG
      production and HLA-DR expression by REF. It thus has potential as a therapeutic
      agent which regulates the function of lymphocytes infiltrating the retro-orbital
      tissues, and which are instrumental in TAO.

PMID- 9761379
TI  - Influence of orchidectomy and ovariectomy on the blood-brain barrier permeability
      during bicuculline-induced seizures.
AB  - The changes in the permeability of the blood-brain barrier (BBB) during
      bicuculline-induced seizures were investigated in ovariectomized female and
      orchidectomized male rats. The rats were anesthetized with diethyl ether. Evans
      blue, which was used as a BBB tracer, was injected into femoral vein 5 min before
      administering bicuculline to induce grandmal seizures. Ten groups of rats were
      studied: Group I: control female; Group II: control male; Group IIl: intact
      female + bicuculline; Group IV: intact male + bicuculline; Group V:
      ovariectomized female; Group VI: orchidectomized male; Group VII: ovariectomized
      female + bicuculline; Group VIII: orchidectomized male + bicuculline (1.2 mg/kg,
      i.v.); Group IX: ovariectomized female + estrogen + bicuculline; Group X:
      orchidectomized male + estrogen + bicuculline. Adult male and female rats were
      orchidectomized and ovariectomized 3 weeks before the experiments, or sham
      operated under general anesthesia. During bicucculline-induced seizures, the mean
      arterial blood pressure increased significantly in both intact and ovariectomized
      and orchidectomized rats. BBB lesions were present in 80 percent of intact female
      rats and 50 percent of ovariectomized rats after bicuculline-induced seizures.
      This difference between intact and ovariectomized rats was found to be
      significant (p < 0.01). There was no statistically significant change in the BBB
      permeability between intact and orchidectomized rats after convulsion. Generating
      seizures in both ovariectomized and orchidectomised rats, after administrating of
      estrogen, did not lead to any significant alteration in BBB permeability. Our
      results suggest that the extravasation of Evans blue albumin was most pronounced
      in the brain of intact female rats when compared to ovariectomized rats after
      bicuculline-induced seizures. After administrating estrogen, the decreased BBB
      permeability values of ovariectomised rats could not reach the values in intact
      rats.

PMID- 9761380
TI  - Comparison of the effects of simmondsin and cholecystokinin on metabolism, brown
      adipose tissue and the pancreas in food-restricted rats.
AB  - In this study, we investigated the analogies between the physiological effects of
      simmondsin, a satiety-inducing glycoside extracted from jojoba seeds, and the
      gastro-intestinal satiation peptide, cholecystokinin. The effects of
      intraperitoneal injection of the biological active CCK-octapeptide on the
      pancreas, interscapular brown adipose tissue, growth performance and energy
      metabolism in normal-fed, severely food intake-restricted (50 % of normal food
      intake) or moderately food intake-restricted (65 % of normal food intake) growing
      rats were compared to the effects of 0.25 % simmondsin mixed in the food,
      inducing moderate food intake reduction (65 % of normal) in rats. Cholecystokinin
      induced pancreatic hypertrophy. In normal fed rats, cholecystokinin had no effect
      on brown adipose tissue or growth, while, in severely food intake-restricted
      rats, it caused brown adipose tissue hypertrophy and reduced growth. In
      moderately food intake-restricted rats, both cholecystokinin and simmondsin
      induced pancreatic hypertrophy, increased brown adipose weight and metabolism and
      caused a slight decrease in growth. We conclude that cholecystokinin may decrease
      growth performance in fast growing severely food intake-restricted rats by
      stimulating brown adipose tissue metabolism, probably because of protein shortage
      induced by pancreatic hyperstimulation. Simmondsin has similar effects. These
      results support the hypothesis that endogenous cholecystokinin is involved in the
      effects of simmondsin in rats.

PMID- 9761381
TI  - Xenotransplantation of adult porcine islets in diabetic mice. A study of UVB
      irradiation, cryopreservation and immunosuppression on graft survival time.
AB  - The major obstacle for successful xenotransplantation of islets to large animals
      and human diabetics is the host rejection. To address the rejection problem, we
      studied the efficacy of UV-B irradiation, cryopreservation and immunosuppression
      on the in vivo functional time and immunogenicity of adult porcine islets (PI) in
      outbred CD1 mice. Exposure of PI to UV-B irradiation between 300-1800J/M2 did not
      affect the cellular viability as assessed by fluorescein diacetate or their daily
      insulin secretion in vitro. Fresh PI normalized the blood glucose (BG) of
      diabetic CD1 mice for 3.1+/-0.6 (n = 8, mean+/-SEM) days. Islets treated with
      600J/M2 UV-B irradiation or cryopreservation had similar graft functional times
      to fresh islets upon transplantation in diabetic CD1 mice. Immunosuppression with
      cyclosporin A (CsA), antilymphocyte serum (ALS) and FK506 prolonged the
      functional time of fresh pig islets to 7.9+/-0.9 (n = 9), 6.2+/-1.3 (n = 5) and
      24.2+/-10.4 (n = 12) days, respectively. However, additional pretransplant
      treatment with either UV-B irradiation or cryopreservation did not further
      increase the functional time of pig islets in mice immunosuppressed with CsA.
      Furthermore, there was no apparent difference in the frequency of appearance of
      cytotoxic antibodies and antibody titers in the recipients of UV-B irradiated or
      cryopreserved pig islet compared with non-treated islets. The UV-B irradiation
      and cryopreservation of PI before transplantation with the present protocols did
      not appear to have significant effect on the islet immunogenicity when assessed
      by in vivo survival duration and anti-donor antibody titer production.

PMID- 9761382
TI  - Nephrectomy decreases amylin and pramlintide clearance in rats.
AB  - Amylin is a 37 amino acid hormone, co-secreted with insulin from the pancreatic
      beta-cell in response to nutrient stimuli. Because the human amylin analog,
      pramlintide, is being tested in patients with diabetes mellitus, a known risk
      factor for nephropathy, we examined the role of the kidney on amylin and
      pramlintide metabolism and action in functionally nephrectomized rats.
      Nephrectomy markedly altered amylin metabolism: it increased incremental area
      under the plasma amylin concentration curve 3.6-fold (P<0.001) and increased the
      elimination half-life from 17+/-1 to 26+/-2 minutes (P < 0.01) after subcutaneous
      injection of 100 microg amylin. Nephrectomy decreased plasma amylin clearance
      from 20.3+/-1.1 to 7.9+/-0.4 mL/min (P < 0.0001). Thus, at these doses in the
      rat, the kidney is important for metabolizing amylin and pramlintide.

PMID- 9761383
TI  - Effects of rat amylin on renal function in the rat.
AB  - Amylin is a peptide secreted from the pancreatic beta-cell along with insulin in
      response to nutrient stimuli. Amylin has been reported to delay gastric emptying,
      inhibit glucagon secretion and gastric acid secretion, increase plasma lactate,
      plasma glucose and plasma renin activity, and decrease plasma calcium. Receptors
      for amylin have been found in the rat nucleus accumbens and the kidney. In the
      present experiments, amylin was administered to anesthetized rats by continuous
      intravenous infusions at varied rates. Amylin significantly increased urine flow
      at an infusion rate resulting in a plasma concentration of approximately 52 pM,
      and at a concentration of approximately 193 pM, it increased sodium excretion,
      glomerular filtration rate and renal plasma flow. Renal calcium and potassium
      excretion were significantly elevated at plasma amylin concentrations of
      approximately 52 pM and 193 pM, respectively. Higher concentrations of plasma
      amylin decreased plasma calcium and potassium and blunted urinary excretion of
      these electrolytes. Thus, of the renal responses tested, diuresis and natriuresis
      appeared to be the most sensitive to infused amylin. These renal effects occurred
      only at plasma concentrations above the normal range, but within the range of
      concentrations reported in insulin resistant rats.

PMID- 9761384
TI  - Peripheral plasma levels of beta-endorphin in alcoholics and highly trained
      athletes and the relationship to a measure of central opioid tone.
AB  - Human beta-endorphin-like immunoactivity was measured in highly trained athletes
      (n = 10), alcoholics in the early phase of abstinence (n=9) and normal controls
      (n=15) using the Nichols Allegro immunoradiometric assay. The assay was examined
      for cross reactivity against related peptides, beta-lipotropin and human N-acetyl
      beta-endorphin. Venous blood sampling was carried out in the morning at 0900 and
      1100 hours in a fasting state. Using two-way analysis of variance there was a
      significant effect of subject group on beta-endorphin concentration (p=0.029).
      Post-hoc analysis using the Bonferroni t-test showed that the source of the
      difference was the alcoholic group having significantly lower beta-endorphin
      immunoreactivity (p < 0.05). There was no difference between the controls and the
      athletes. There was a positive correlation between plasma beta-endorphin level at
      1100 hours and the subsequent ACTH incremental response to naloxone in the group
      as a whole (r=0.48, p=0.004). The assay showed 100% cross reactivity with beta
      lipotropin and 73% cross reactivity with N-acetyl-beta-endorphin. We conclude
      that alcoholics have reduced levels of beta-endorphin-like immunoactivity. While
      beta-endorphin is known not to cross the blood-brain barrier, levels of plasma
      beta-endorphin-like immunoactivity may indirectly reflect central opioid
      activity.

PMID- 9761385
TI  - Decreased in vitro IL-4 [corrected] and IL-10 production by peripheral blood in
      first degree relatives at high risk of diabetes type-I.
AB  - There is mounting evidence that the imbalance between Th1 and Th2 lymphocyte
      subsets plays a key role in the development of autoimmune diabetes in NOD mice,
      but it is also possible in humans. The aim of the present study was the
      estimation of in vitro production of Th1 (INF-gamma, IL-2) and Th2-derived (IL-4,
      IL-10) cytokines by peripheral blood in ICA and GADA positive first degree
      relatives of Type-I diabetes patients, since they could represent primary events
      triggering an immune-mediated islets destruction. The study was performed in 25
      subjects at risk of insulin-dependent diabetes and 21 age- and sex-matched
      healthy controls. Cytokine levels in supernatants of whole blood cultures with
      PHA (10 microg/ml) were quantified by ELISA. We observed a lower concentration of
      IL-4 in culture supernatants in ICA and GADA positive relatives as compared with
      the control group, both at 48 h and at 72 h of incubation. Similarly, in the
      prediabetic group, lower IL-10 levels at 48 and 72 h of culture were found. We
      did not observe statistical differences in in vitro production of IL-2 and INF
      gamma by peripheral blood in high risk diabetes mellitus subjects and healthy
      controls. In subjects at increased risk of Type-I diabetes, levels of IL-4
      positively correlated with those of IL-10. There were negative correlations
      between IL-10 concentration after 48 h of incubation and levels of HbA1C. In
      conclusion our study has shown decreased IL-4 and IL-10 production, but normal
      secretion of Th1-derived cytokines by peripheral blood of prediabetic humans.
      This could suggest that the early stage of autoimmune process in Type-I diabetes
      in humans is associated with decreased function of Th2-cells rather than
      overactivation of Th1 subset in the peripheral blood.

PMID- 9761386
TI  - Power spectral analysis of variations in heart rate in patients with
      hyperthyroidism or hypothyroidism.
AB  - Power spectral analysis (PSA) of the variation in heart rate is useful in
      determining the relative activity of the sympathetic and parasympathetic nerves.
      In this study, PSA was used to investigate the relationship between abnormalities
      in autonomic nerve function and the presence of thyroid disorders in patients
      with autoimmune thyroid diseases. The low frequency (LF) or high frequency (HF)
      components of R-R variations were determined by PSA. The coefficient of variation
      of the R-R time intervals (CV(R-R)) was positively correlated with HF in healthy
      subjects. In untreated hyperthyroid patients with Graves' disease, the CV(R-R)
      and HF values were significantly lower than in healthy controls. Moreover, the
      LF/HF ratio in patients with untreated Graves' disease was significantly higher,
      and the LF/HF ratio in hypothyroid patients with Hashimoto's thyroiditis was
      significantly lower than in healthy controls. A negative correlation was observed
      between serum levels of free thyroid hormones (FT4 and FT3) and HF in Graves'
      disease patients. In some hyperthyroid patients, antithyroid drug therapy or beta
      blocker administration gradually restored reduced HF values. Present results
      suggest that relative vagal nerve activity is reduced in hyperthyroid patients
      and that this reduction is reversible according to the decrease in serum levels
      of thyroid hormones.

PMID- 9761387
TI  - Ultrasound transmission speed and ultrasound bone profile score (UBPS) of the
      phalanges in normal women and women with osteoporosis.
AB  - The distal metaphysis of the first phalanx of the fingers II-V is, like the
      vertebral body, a useful site for the measurement of mineralisation and structure
      of the bone because of the simultaneous presence of compact and trabecular bone.
      With an ultrasound device (DBM sonic 1200, IGEA, Italy), we measured the adSOS
      (the amplitude dependent speed of sound) and the UBPS (ultrasound bone profile
      score), a score which is calculated from the graphic traces of the receiving
      probe with an expert system which uses fuzzy-logic at phalanges II-IV, as well as
      bone mineral density (BMD) at lumbar spine using dual X-ray absorptiometry (DXA).
      Precision of the measurements was as follows: adSOS: short-time-CV% = 0.576, long
      time-CV% = 1.1, SCV% = 5.9, RMSSD% = 1.825. UBPS: short-time CV% = 5.95. There
      was no correlation between adSOS or UBPS and lumbar BMD (DXA). There was a
      significant positive correlation between adSOS and UBPS, r = 0.804 (p<0.00001).
      The validity of adSOS and UBPS was examined in 25 young and healthy women (mean
      age: 33.4 year), 15 postmenopausal healthy women (mean age: 58.5 years), 17 women
      with osteopenia, (mean age: 52.4 years), as defined by a t-score between -1 to 
      2.5 SD as lumbar BMD (DXA), and 20 women with osteoporosis and vertebral
      fractures (mean age: 61.4 years). We compared the healthy postmenopausal women
      and the women with osteoporotic vertebral fractures, the z-score of the adSOS was
      below minus 1.5 SD and UBPS was below 40, sensitivity was 0.7 for adSOS, and 0.85
      for UBPS, with a specificity 0.97 for adSOS, and of 0.93 for UBPS; positive
      predictive value: adSOS: 0.93, UBPS: 0.85. AdSOS declined with age (r= 0.694,
      p=0.021); the UBPS was not age dependent (r=-0.15, p = n.s.). The ROC-curve shows
      a value of 0.96 for adSOS and 0.94 for UBPS. AdSOS and UBPS could discriminate
      well between the healthy controls and the women with osteopenia or vertebral
      fractures (p<0.00001). These results show that adSOS and UBPS are precise
      parameters to be measured at the phalanges. The detection level of pathological
      changes in osteoporosis are similar between adSOS and lumbar BMD (DXA) and
      improved by using the UBPS. This might be explained by the influence of
      structural changes in bone on UBPS, rather than change in bone mineral alone.
      Prospective studies have to clarify the role of adSOS and UBPS in fracture
      prediction.

PMID- 9761388
TI  - The yeast genome and clinical genetics.

PMID- 9761389
TI  - Genetic landmarks through philately--Gregor Johann Mendel (1822-1884).

PMID- 9761390
TI  - Life expectancy in British Marfan syndrome populations.
AB  - A total of 206 patients with Marfan syndrome were ascertained throughout genetic
      clinics in Wales and Scotland during the period 1970-1990. There were 45 deaths
      representing 22% of the cohort. Mean age at death was 45.3+/-16.5 years. 50%
      median cumulative survival in the total cohort (n=206) was 53 years for males and
      72 years for females. Multivariate analysis confirmed severity as the best
      independent indicator of survival. These findings and survival curves will assist
      in the counselling of British families and individuals with Marfan syndrome.

PMID- 9761391
TI  - A gene-dosage PCR method for the detection of elastin gene deletions in patients
      with Williams syndrome.
AB  - Williams syndrome (WS) is a multisystem developmental disorder associated with
      microdeletions at 7q11.23 that involve several genes, including the elastin gene.
      Using genomic DNA from a panel of normal individuals and WS patients with
      established hemizygosity of the elastin gene locus, we have developed a
      quantitative polymerase chain reaction (PCR)-based gene-dosage assay that rapidly
      detects the loss of one allele of the elastin gene. Using this procedure, we also
      studied a family in which the proband was previously diagnosed with WS and her
      mother with a balanced 7q translocation [t(7:11)(q34;q13)]. Using DNA isolated
      from buccal smears obtained from several individuals in this family we were able
      to establish normal disomy at 7q in all family members except for the proband, in
      which we established hemizygosity at the elastin gene locus. We were also able to
      successfully infer normal disomy in an unborn child in this family. The rapid
      diagnostic procedure described here may have a variety of applications, including
      fine mapping of deletion breakpoints at 7q11.23 associated with WS.

PMID- 9761392
TI  - Neuropathological findings in Moebius syndrome.
AB  - Pathological findings in two patients with Moebius syndrome and lethal fetal
      akinesia sequence are described. In both patients a congenital brain stem
      malformation with neuronal loss in the cranial nerve nuclei and tegmental
      microcalcifications was observed. In one patient, the association with
      splenogonadal fusion was observed, whilst in the second patient, the association
      with tetraperomelia was present. As the association of peromelia and
      splenogonadal fusion is a well-known association, the different combination of
      splenogonadal fusion, peromelia and Moebius syndrome due to congenital brain stem
      anomalies with necrosis might be the result of a disruptive phenomenon during a
      prolonged vulnerable critical period in the 5th and 6th week of embryonic life.
      The finding of olivary dysplasia in one case, reminiscent of olivary dysplasia in
      Zellweger syndrome and in Miller Dieker syndrome, might suggest a primary
      malformation underlying Moebius syndrome due to brain stem defects.

PMID- 9761393
TI  - Molecular analysis of the BRCA2 gene in 16 breast/ovarian cancer Spanish
      families.
AB  - The recent isolated gene BRCA2 is responsible for about 45% of familial breast
      cancer and the majority of male breast cancer families. In order to evaluate the
      role of inherited BRCA2 mutations in Spanish families, the complete coding
      sequence of the gene was screened by SSCP/sequencing in 16 high-risk
      breast/ovarian cancer families. Four mutations were found that cause a premature
      termination codon. Two of them have been reported elsewhere and one is a novel
      mutation. In addition we have found seven polymorphisms, two of which have not
      been previously described. One of the mutations, 936delAAAC was found in two of
      our high-risk families. Because this mutation is considered as recurrent, we have
      tried to estimate its frequency in our breast cancer population. A total of 127
      moderate- high-risk families were screened for this mutation and it was also
      found in another high-risk family. All the families carrying the 936delAAAC
      mutation harboured part of a common haplotype shared by other reported carriers,
      suggesting a possible founder effect for this mutation.

PMID- 9761394
TI  - Spinal and bulbar muscular atrophy (SBMA): somatic stability of an expanded CAG
      repeat in fetal tissues.
AB  - Spinal and bulbar muscular atrophy (SBMA) is a rare X-linked motor neuron
      degenerative disease caused by an expanded trinucleotide repeat. Unlike most
      other trinucleotide repeat diseases, SBMA shows limited meiotic instability, and
      evidence thus far indicates absence of somatic instability in adults. Data
      regarding the presence of fetal tissue somatic mosaicism is unavailable. We
      present a family in which a woman whose father had SBMA requested prenatal
      testing. After informed consent. molecular genetic evaluation showed the male
      fetus to carry the SBMA repeat elongation. Testing of fetal tissues after
      elective pregnancy termination showed no somatic mosaicism in the CAG repeat
      length. This is the first report of molecular genetic analysis of multiple
      tissues in an affected fetus, and only the second report of prenatal diagnosis in
      SBMA.

PMID- 9761395
TI  - Polymorphic variants within the homeobox gene MSX1: a candidate gene for
      developmental disorders.

PMID- 9761396
TI  - Map refinement of the Usher syndrome type 1B gene, MYO7A, relative to 11q13.5
      microsatellite markers.
AB  - Usher syndrome (US) is clinically and genetically a heterogeneous group of
      disorders characterized by the association of deafness with retinitis pigmentosa.
      So far, eight genes responsible for US have been mapped, of which only the gene
      responsible for the most common form, USH1B, has been identified. The USH1B is a
      large gene containing 49 exons and encoding for an unconventional myosin-VIIA
      (MYO7A). Mutation analysis within the MYO7A gene showed a wide variety of
      mutations dispersed all over the gene. The present report refines the location of
      the MYO7A gene relative to microsatellite markers mapped to this region, thereby
      allowing a reliable and efficient carrier detection by linkage analysis.

PMID- 9761397
TI  - Involvement of 9q22.1-31.3 region in pyloric stenosis.

PMID- 9761398
TI  - The common features of patients with partial trisomy of the long arm of
      chromosome 1.

PMID- 9761399
TI  - Monozygotic monoamniotic twins discordant for urethral and anal atresia with
      vesicorectal fistula: a favourable combination of defects.

PMID- 9761400
TI  - Prevalence of high affinity IgE receptor [Fc epsilon RI beta] gene polymorphisms
      in Kuwaiti Arabs with asthma.

PMID- 9761401
TI  - Debriefing after psychological trauma.

PMID- 9761402
TI  - The treatment of social phobia: a critical assessment.
AB  - This article critically reviews the effects of psychological treatment (exposure,
      cognitive restructuring, social skills training) and pharmacological treatment
      (MAOIs, reversible MAOIs, anxiolytics and SSRIs) of social phobia. Only
      controlled studies have been included, and their outcomes were assessed for
      improvement in anxiety and avoidance, social functioning and clinical status.
      Both psychological and pharmacological treatments resulted in a significant and
      meaningful reduction in anxiety and, in most cases, a weakening of the tendency
      to avoid. Although useful, the effects were not of such a magnitude as to result
      in remission. Reduction in anxiety was long-lasting in patients treated by
      psychological methods. The lessening of anxiety did not necessarily lead to
      meaningfully improved social functioning. The combination of psychological and
      pharmacological treatments was disappointing, and did not exceed the effects of
      psychological treatments alone. However, the most promising medications were not
      tested. Subtype of social phobia and additional diagnoses did not determine the
      response to treatment.

PMID- 9761403
TI  - Mental health expectancy: an indicator to bridge the gap between clinical and
      public health perspectives of population mental health.
AB  - Mental health indicators generally used in public health are derived from
      mortality statistics, but they do not reflect the impact that disability due to
      mental disorders has on population health. The present study proposes a global
      indicator of population mental health which combines both mortality and morbidity
      data. The data used were the results of a Health Interview Survey, including the
      12-item version of the General Health Questionnaire, mortality life-tables for
      the general population, and data from a two-step epidemiological study used to
      assign the probability of case status. The results are calculated for the
      Catalonia region in north-east Spain. Life expectancy and mental health
      expectancies at all ages were found to be higher for women than for men. Men were
      found to have a higher total life expectancy in good mental health. The
      feasibility and potential areas of application of this generic mental health
      index are discussed.

PMID- 9761404
TI  - Depressive disorders among somatizing patients in primary health care.
AB  - Unrecognized, untreated and undertreated depressive disorders incur inordinate
      human and economic costs, despite the availability of an exclusive array of
      clinical interventions. The aim of this study was to identify cases of masked
      depression in primary health care, employing a two-stage design. In the first
      stage, involving a study of 442 patients, the prevalence of recognized depression
      was 1.8%. In the second step, 62 patients from stage 1 were investigated further
      because of their high score on somatization tendency. In total, 41 of the 62
      patients were found to have a mood disorder according to DSM-III-R, i.e. a major
      depressive disorder or dysthymia. Two patients were found to have already had a
      diagnosis of major depression assigned to them in stage 1, but they were joined
      by 13 more patients. A further 26 patients were found to be suffering from
      dysthymia, nine had adjustment disorders with depressed mood, and 12 patients
      showed no signs of depressed mood. For the group suffering from a current episode
      of major depression or dysthymia, the prevalence rate increased to 11.7% in the
      initial total population after stage 2. The diagnostic category with the highest
      rate of depressed patients was 'musculoskeletal diseases'. Patients with masked
      depression had higher scores for alexithymia and psychasthenia than depressed
      patients who were directly diagnosed.

PMID- 9761405
TI  - Regional differences in the use of psychiatric hospital beds in Finland: a
      national case-register study.
AB  - We investigated the possible differences in the utilization of psychiatric
      hospital beds among five social security areas in Finland, and the association
      between the variables related to the psychiatric services and the use of hospital
      beds. The use of hospital beds varied quite distinctly among these areas, as did
      the total rate of in-patients, readmissions, and rates of in-patients with
      psychotic and affective disorders. The treatment practices appeared to vary as
      the length of stay (LOS) and the rate of committal differed regionally in a
      significant manner. There was a significant positive correlation between the
      total rate of in-patients and the rate of readmitted patients (r=0.92, P<0.001),
      and a significant negative correlation between the number of visits per worker in
      out-patient care and the rate of readmissions (r=-0.94, P<0.001).

PMID- 9761406
TI  - A 16-year follow-up study of schizophrenia and related disorders in Sofia,
      Bulgaria.
AB  - A total of 60 patients with functional non-affective psychoses were assessed 16
      years after their inclusion in the WHO co-ordinated study on reduction and
      assessment of psychiatric disability. All patients at inclusion had a recent
      onset of a psychotic disorder. About one-third of the patients had a good
      outcome. The rest showed moderate to severe psychiatric symptoms and social
      disability. Comparison with other similar studies suggested that our results show
      a low mortality rate, high levels of clinical symptoms, high levels of social
      disability and a low percentage of institutionalized patients. These findings are
      discussed in the context of the high level of family involvement in patients'
      care, which could reflect a cultural factor.

PMID- 9761407
TI  - Repetition of parasuicide--ICD-10 personality disorders and adversity.
AB  - Patients with a history of previous parasuicide were compared to those who had
      made their first attempt. A scale for suicidal ideation derived from the Scaled
      Version of the General Health Questionnaire was completed by patients. ICD-10
      personality disorder diagnoses were derived from the Standardized Assessment of
      Personality which was administered to knowledgeable informants. Logistic
      regression showed that unemployment, increasing severity of suicidal ideation,
      previous psychiatric treatment and borderline personality disorder increased the
      risk of reports of previous parasuicide. Anankastic personality disorder
      decreased the risk of reports of previous parasuicide. Unemployment and specific
      personality disorders have independent risks for repetition of parasuicide.
      Specific ICD-10 personality disorders may increase or decrease the risk for
      repetition of parasuicide.

PMID- 9761408
TI  - Suicides hidden among undetermined deaths.
AB  - The research phase of the National Suicide Prevention Project in Finland (from 1
      April 1987 to 31 March 1988) included medico-legal investigation and
      psychological autopsy of all deaths suspected of being suicides, including 1397
      official suicides and 61 undetermined deaths. In later analyses on suicide,
      undetermined cases were excluded. This paper presents an analysis of all
      officially classified undetermined deaths (n = 139) over the study period,
      consisting of all the initially suspected suicides (n = 61) and the remaining
      undetermined deaths (n = 78) where suicide could not be excluded. Poisoning by
      solids or liquids and drowning were the most common causes of all undetermined
      deaths. Suicidal intent was observed in 87% of undetermined deaths initially
      suspected of being suicides. In addition, 31% of these subjects had previously
      attempted suicide, and 34% had made suicidal threats. Depression was diagnosed in
      23% of cases and alcohol dependence or abuse in 31% of cases. Undetermined deaths
      resembled suicides and appeared to reduce the suicide rate by 10%.

PMID- 9761409
TI  - Development and preliminary application of a new scale for assessing
      dysfunctional working models of self and others (DWM-S) in severely disturbed
      patients.
AB  - Although several suggestions have been made concerning the content and
      characteristics of cognitive/emotive schemata held by people with different
      disorders, there is still a scarcity of suitable instruments for verifying or
      measuring such constructs. This is particularly true of schemata postulated to be
      present in patients with personality disorders or a schizophrenic disorder. This
      article deals with the development of a new scale for assessing dysfunctional
      internal working models of self and others (DWM-S) in psychiatric patients.
      Preliminary results obtained in a sample of patients (n=110) and healthy subjects
      (n=40) suggest that the scale has a highly satisfactory internal consistency
      (Cronbach's alpha=0.97), and satisfactory test-retest reliability (rho
      coefficient=0.90 in healthy subjects and 0.86 in patients). Moreover, the DWM-S
      is able to discriminate between patients and healthy subjects and between
      patients suffering from various disorders. Further studies are in progress to
      assess the cross-national generalizability of the findings obtained so far.

PMID- 9761410
TI  - A comparison of the performance of rating scales used in the diagnosis of
      postnatal depression.
AB  - The results of a study looking into the association between thyroid status and
      depression in the postpartum period were reanalysed to explore the psychometric
      properties of the rating scales employed. The performance of the Edinburgh
      Postnatal Depression Scale was found to be superior to that of the Hospital
      Anxiety and Depression Scale in identifying RDC-defined depression, and on a par
      with the observer-rated Hamilton Rating Scale for Depression, which it also
      matched for sensitivity to change in mood state over time. The anxiety subscale
      of the Hospital Anxiety and Depression Scale performed well, reflecting the fact
      that anxiety represents a prominent symptom in postnatal depression.

PMID- 9761411
TI  - TCI temperamental scores in bulimia nervosa patients and normal women with and
      without diet experiences.
AB  - In order to distinguish the trigger and the factors maintaining bulimia nervosa
      (BN), TCI temperamental scores were compared among BN patients, normal controls
      without diet experiences (N-N), and normal controls with diet experiences (N-D).
      On the novelty-seeking (NS) scale, the BN patients scored significantly higher
      than the N-N subjects, but there was no significant difference between the BN
      patients and the N-D subjects, and the N-D subjects scored higher than the N-N
      subjects. These findings suggest that high NS scores are related to diet
      experiences rather than chronic bulimic symptoms.

PMID- 9761412
TI  - Behaviour/emotional problems in male juvenile delinquents and controls in Russia:
      the role of personality traits.
AB  - Recent studies based on the psychobiological theory of personality by Cloninger
      postulate a relationship between certain personality traits and various
      psychopathological manifestations. To test this theory, we administered the
      Temperament and Character Inventory and the Youth Self-Report to 188 male
      delinquents from a juvenile correction centre in Northern Russia, and to 111 age
      matched male controls recruited from among schoolchildren. As assumed by previous
      studies, psychological symptoms were primarily positively correlated with harm
      avoidance and negatively correlated with self-directedness. At the same time, the
      higher levels of aggressive and delinquent behaviour were positively correlated
      with novelty-seeking and negatively correlated with co-operativeness. The
      possible mechanisms underlying these findings are discussed.

PMID- 9761413
TI  - Debriefing with brief group psychotherapy in a homogenous group of non-injured
      victims of a terrorist attack: a prospective study.
AB  - This study describes a follow-up of 15 non-injured women, all from the same socio
      economic background, who were exposed to a terrorist attack in Israel. All of the
      women participated in group debriefing with brief group psychotherapy, involving
      six meetings during the first 2 months following the event. Two days after the
      attack, and 2 months and 6 months after the event, the women were administered a
      post-traumatic stress disorder (PTSD) diagnostic scale, the Impact of Event Scale
      (IES) and the SCL-90. At 6 months, four subjects (27%) were diagnosed with full
      PTSD. The IES showed significantly higher scores at the first measure than at the
      other two measures. Furthermore, the phobic anxiety subscale score immediately
      after the event was significantly associated with the General Severity Index of
      the SCL-90 and the severity of PTSD symptomatology at 6 months. The present paper
      discusses the effectiveness of psychological intervention following trauma, and
      raises questions concerning the need to invest public resources in this kind of
      intensive intervention. Suggestions are proposed regarding the desired emphasis
      of the psychological treatment in order to improve its benefits to victims.

PMID- 9761414
TI  - Personality disorders and relationship to personality dimensions measured by the
      Temperament and Character Inventory in patients with obsessive-compulsive
      disorder.
AB  - The occurrence of personality disorders was investigated in 36 patients with
      obsessive-compulsive disorder by means of the SCID Screen questionnaire. In
      addition, the personality dimensions were explored by means of the Temperament
      and Character Inventory (TCI). In total, 75% of the patients fulfilled the
      criteria for a personality disorder according to the SCID Screen questionnaire,
      mostly (55%) within cluster C. Several significant correlations were found
      between the separate personality disorders (PD) and subscales of the TCI, the
      most pronounced being between avoidant and obsessive-compulsive PD and novelty
      seeking and self-directedness. Strong correlations were also found between self
      directedness and paranoid and borderline PD. In multiple regressions where the
      presence of PD in clusters A, B and C, respectively, were used as dependent
      variables and where the separate subscales of the TCI were used as independent
      variables, the multiple R reached 0.68, 0.76 and 0.80 in clusters A, B and C,
      respectively. Thus 46-64% of the variance in the personality disorder clusters
      could be explained by the TCI subscales.

PMID- 9761415
TI  - Severity of psychiatric disorder in day hospital and in-patient admissions.
AB  - This study assessed whether severity of psychiatric disorder varies across day
      hospital and in-patient units according to local need, and whether severity of
      disorder predicts length of stay and therefore costs. Data were collected for a
      consecutive series of 2230 in-patients and 712 day patients using the Social
      Behaviour Scale (data completed by nurses) and diagnosis and Clinical Global
      Impression (CGI) (completed by doctors). Severity of illness of subjects admitted
      to in-patient units, but not to day hospitals, was associated with under
      privileged area score (UPA). Length of in-patient stay is most accurately
      predicted by Clinical Global Impression and six other variables relating to
      diagnosis, demographic status and individual hospital. Improved resource
      allocation for mental health services could be achieved if severity of disorder
      was routinely collected.

PMID- 9761416
TI  - Marijuana precipitation of panic disorder with agoraphobia.
AB  - We report the case of a 16-year-old adolescent with the onset of a panic disorder
      with agoraphobia after a first panic attack during marijuana intoxication. There
      was a good response to standard cognitive behavioural therapy for panic disorder.

PMID- 9761417
TI  - Enhancement of immobility in mouse forced swimming test by treatment with human
      interferon.
AB  - We investigated the depression induced by human interferons using the forced
      swimming test in mice. Intravenous (i.v.) administration of interferon-alpha s
      (natural interferon-alpha, recombinant interferon-alpha-2a and recombinant
      interferon-alpha-2b, 600-60000 IU/kg) increased the immobility time in the forced
      swimming test in a dose-dependent manner, but natural interferon-beta and
      recombinant interferon-gamma-1a did not affect the immobility time. The increase
      in the immobility time induced by recombinant interferon-alpha-2b peaked at 15
      min after dosing. Administration of recombinant interferon-alpha-2b (6000 IU/kg,
      i.v.) once daily for 7 consecutive days increased the immobility time, but
      natural interferon-beta and recombinant interferon-gamma-la did not. Recombinant
      interferon-alpha-2b in combination with the anti-depressants imipramine (10
      mg/kg, i.p.) and mianserin (20 mg/kg, i.p.) did not increase the immobility time.
      These results suggest that interferon-alpha has a greater potential for inducing
      depression than interferon-beta and -gamma, and that anti-depressants are
      effective against interferon-alpha-induced depression.

PMID- 9761418
TI  - Functional determination of oxytocin affinity in near-term pregnant rat
      myometrium: effect of chronic hypoxia.
AB  - We designed the present study to determine: (1) if phenoxybenzamine can be used
      as an irreversible blocker for oxytocin receptors, and as such to determine
      oxytocin affinity, (2) if prolonged hypoxic exposure alters oxytocin receptor
      coupling efficacy of oxytocin receptors to post-receptor mediated mechanisms in
      the rat myometrium. Rats were exposed to room air (control), or to continuous
      hypoxia (10.5% O2) from day 19 through day 21 (2-day exposure). On day 21, one
      uterine horn was removed and used for in vitro study of myometrial contractile
      responses to oxytocin, while the other was used for oxytocin receptor analysis.
      In normoxic tissues, phenoxybenzamine (20 microM) decreased the maximum
      contractile response (EMAX) to oxytocin (155+/-17 vs. 66+/-19 g s/cm2) and
      oxytocin binding sites (BMAX: 253+/-35 vs. 114.9+/-21.3 fmol/mg protein). A
      similar degree of reduction in EMAX and BMAX were observed in hypoxic tissues.
      The oxytocin dissociation constant (KA) in the normoxic rat was 2.8+/-0.7 nM,
      which was not different from the chronic hypoxic rat (3.3+/-0.9 nM). Analysis of
      receptor occupancy-response curves indicated no oxytocin receptor reserve in both
      normoxic and hypoxic myometrium. However, for a given fraction of the total
      oxytocin receptors occupied, hypoxic tissue elicited a lower contractile response
      to oxytocin. We conclude that: (1) phenoxybenzamine is a useful tool to
      functionally study oxytocin receptor kinetics, (2) prolonged hypoxic exposure
      does not affect the oxytocin affinity, (3) no spare receptors for oxytocin are
      present in the rat myometrium, and (4) prolonged exposure to hypoxia decreases
      oxytocin receptor-effector coupling efficiency in rat myometrium.

PMID- 9761419
TI  - External carotid effects of 2-(2-aminoethyl)-quinoline (D-1997) in
      vagosympathectomized dogs.
AB  - Serotonin (5-hydroxytryptamine; 5-HT) elicits external carotid vasoconstriction
      in vagosympathectomized dogs via 5-HT1B/1D receptors and a mechanism unrelated to
      the 5-HT1, 5-HT2, 5-HT3 and 5-HT4 types. In order to further explore the nature
      of this novel mechanism, the canine external carotid effects of 2-(2-aminoethyl)
      quinoline (D-1997), a novel 5-HT1 receptor agonist, were analyzed and compared
      with those of 5-HT and sumatriptan. Intracarotid (i.c.) infusions of 5-HT, D-1997
      and sumatriptan to vagosympathectomized dogs dose-dependently decreased external
      carotid conductance, the rank order of agonist potency being 5-HT > sumatriptan >
      D-1997. The effects to D-1997 were resistant to intravenous (i.v.) pretreatment
      with 5-HT2 and 5-HT3/5-HT4 receptor antagonists. Remarkably, the effects induced
      by lower (10-100 microg/min), but not higher (300-1000 microg/min), doses of D
      1997 were blocked by high doses of methiothepin (1 and 3 mg/kg, i.v.), as
      previously shown with 5-HT. In addition, GR-127935 (1-10 microg/kg, i.v.),
      partially and dose-dependently antagonized D-1997-induced responses. However, the
      effects of D-1997 remained unaltered after blockade of alpha- and beta
      adrenoceptors, muscarinic, nicotinic, histamine and dopamine receptors, or
      inhibition of 5-HT-uptake or cyclo-oxygenase, depletion of biogenic amines or
      blockade of Ca2+ channels. These results may support our previous contention that
      lower doses of 5-HT elicit external carotid vasoconstriction in
      vagosympathectomized dogs by activation of 5-HT1B/1D receptors, whilst higher
      doses of 5-HT stimulate a novel vasoconstrictor mechanism.

PMID- 9761420
TI  - Persistent release of noradrenaline caused by anticancer drug 4'-epidoxorubicin
      in rat tail artery in vitro.
AB  - Anthracycline derivatives including 4'-epidoxorubicin are known to cause
      cardiovascular side effects. In this study we examined the effects of 4'
      epidoxorubicin on sympathetic nerves of rat tail artery in vitro. Treatment with
      4'-epidoxorubicin at concentrations higher than 10 microM gradually increased the
      resting tension of the arterial strips, an effect which was greatly enhanced by
      subsequent addition of 10 microM cocaine. This increase of the resting tension by
      4'-epidoxorubicin was prevented by prazosin, suppressed in the arterial strips of
      reserpine-pretreated rats, and reduced by superoxide dismutase. However,
      tetrodotoxin and histamine receptor antagonists (diphenhydramine and cimetidine)
      failed to influence it. The contractile response to electrical sympathetic
      stimulation was slightly attenuated by 30 microM 4'-epidoxorubicin. 4'
      epidoxorubicin did not shift the concentration-response curve for noradrenaline.
      In the superfusion experiments, the basal release of noradrenaline was increased
      approximately five-fold by 30 microM 4'-epidoxorubicin, and this increase was not
      inhibited by 0.1 microM prazosin, 0.5 microM tetrodotoxin, 10 microM cocaine or
      Ca2+-free medium. Noradrenaline release evoked by electrical stimulation was
      gradually suppressed by 30 microM 4'-epidoxorubicin treatment. These results
      suggest that 4'-epidoxorubicin directly acts on the sympathetic nerve to cause
      persistent release of noradrenaline in rat tail artery.

PMID- 9761421
TI  - Effects of pilsicainide and propafenone on vagally induced atrial fibrillation:
      role of suppressant effect in conductivity.
AB  - The effects of pilsicainide on vagally induced atrial fibrillation and on
      electrophysiological parameters were compared with those of propafenone in alpha
      chloralose-anesthetized dogs. Conduction velocity, effective refractory period,
      wavelength, averaged atrial fibrillation cycle length and activation sequence in
      the right atrial free wall were determined before and after drug administration.
      Pilsicainide (2 mg/kg/5 min and 3 mg/kg/h)(n=10) or propafenone (2 mg/kg/15 min
      and 4 mg/kg/h)(n=10) was intravenously infused during stable atrial fibrillation
      sustaining > 30 min. Pilsicainide terminated atrial fibrillation in nine dogs,
      while propafenone did so in three (p < 0.01). After the drug, conduction velocity
      was suppressed more in the pilsicainide than in the propafenone group(p < 0.01).
      There was no difference in effective refractory period after drug between the two
      groups. Mean wavelength was prolonged from 46.0 to 70.4 mm in the pilsicainide
      group and from 45.0 to 110.8 mm in the propafenone (p < 0.01 vs. pilsicainide).
      Activation mapping during atrial fibrillation showed Type II or III atrial
      fibrillation as previously defined [Konings, K.T.S., Kirchhof, C.J.H.J., Smeets,
      J.R.L.M., Wellens, H.J.J., Penn, O.C., Allessie, M.A., 1994. High-density mapping
      of electrically induced atrial fibrillation in humans. Circulation. Vol. 89, pp.
      511-521.] before the drug, and changed to Type I before atrial fibrillation
      termination. Thus, pilsicainide was more effective to terminate vagally induced
      atrial fibrillation than was propafenone despite a greater effect of propafenone
      than of pilsicainide on wavelength. In this canine atrial fibrillation model, the
      suppression of conduction velocity may play an important role in changing the
      activation pattern of atrial fibrillation and thus, terminating atrial
      fibrillation.

PMID- 9761422
TI  - Effect of xanthine oxidase inhibition on endothelium-dependent and nitrergic
      relaxations.
AB  - The effects of inhibition of xanthine oxidase on responses mediated by nitric
      oxide (NO) were examined using the selective xanthine oxidase inhibitors
      allopurinol and 4-amino-6-hydroxypyrazolo[3,4-d]pyrimidine (AHPP). In rat aortic
      rings precontracted with phenylephrine (1 microM), allopurinol (300 microM) and
      AHPP (100, 300 microM) significantly reduced tone, an effect not seen after
      inhibition of NO synthase with Nomega-nitro-L-arginine (NOLA 100 microM).
      Relaxations produced by acetylcholine (0.01-10 microM) were significantly
      enhanced by AHPP (100, 300 microM) but not by allopurinol. Nitrergic relaxations
      in the rat anococcygeus muscle (field stimulation 1 ms pulses; 1 Hz: 10 s) were
      not affected by either allopurinol or AHPP. However, relaxations produced by
      exogenous NO (0.25 microM) were significantly enhanced by AHPP, allopurinol (100
      microM) and superoxide dismutase (100 U/ml). Xanthine (500 microM) partially, but
      significantly, reversed the enhancement produced by AHPP. These findings suggest
      that superoxide generated by xanthine oxidase modulates the activity of basal and
      stimulated NO derived from the rat aortic endothelium, but does not affect the
      activity of the nitrergic transmitter in the rat anococcygeus muscle, despite its
      ability to modulate responses to exogenous NO.

PMID- 9761423
TI  - In vitro comparison of two NONOates (novel nitric oxide donors) on rat pulmonary
      arteries.
AB  - The pulmonary vasorelaxant properties of two NONOates (diazeniumdiolates) were
      examined because this novel group of nitric oxide (NO) donors may be useful in
      pulmonary hypertension. MAHMA NONOate ((Z)-1-?N-Methyl-N-[6-(N
      methylammoniohexyl)amino]? diazen-1-ium-1,2-diolate) and spermine NONOate ((Z)- 1
      ?N-[3-aminopropyl]-N-[4-(3-aminopropylammonio)butyl]-amino?di azen-1-ium-1,2
      diolate) decomposed at different rates (half-lives 1.3 min and 73 min,
      respectively; 37 degrees C, pH 7.3) but generated the same total amount of NO.
      They fully relaxed submaximally contracted ring preparations of main and
      intralobar pulmonary arteries from rats. Responses were inhibited by the
      guanylate cyclase inhibitor, ODQ (1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one).
      Potency was not affected by choice of contractile spasmogen (phenylephrine,
      endothelin-1, thromboxane-mimetic) or endothelium removal, and tolerance did not
      develop; thus the drugs had properties important for use in pulmonary
      hypertension. MAHMA NONOate was 10-40-fold more potent than spermine NONOate but
      responses to spermine NONOate were more sustained (spermine NONOate > 60 min;
      MAHMA NONOate < 7 min). It is concluded that the differences in potency and time
      course reflect the different rates of NO generation by these NONOates.

PMID- 9761424
TI  - Alpha2-adrenoceptors mediate the effect of dopamine on adult rat jejunal
      electrolyte transport.
AB  - The present study was aimed to characterise the effect of dopamine on rat jejunal
      electrolyte transport and to evaluate the type of receptors and the intracellular
      signalling mechanisms involved in the response. Stripped epithelial sheets were
      mounted in Ussing chambers connected to an automatic voltage current clamp and
      changes in the short circuit current (microA/cm2) were measured continuously as
      an index of electrogenic ion transfer. Dopamine (0.1-100 microM) produced a
      concentration dependent decrease in Isc with an EC50 of 1.4+/-0.1 microM: the
      effect of dopamine was not changed by propranolol (1 microM), prazosin (1 microM
      and 10 microM) or (+/-)-sulpiride (1 microM). but was completely abolished by
      phentolamine (1 microM). The addition of phentolamine (0.3 microM) or yohimbine
      (0.3 microM) produced a rightward shift of the dopamine concentration-dependent
      curve with an increase in EC50 values up to 30.0+/-0.2 microM and 11.7+/-0.1
      microM. respectively. The alpha2-adrenoceptor-selective agonist, UK14,304 (5
      bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine), also produced a
      concentration-dependent decrease in Isc with an EC50 of 0.04+/-0.01 microM; the
      addition of yohimbine (0.3 microM) increased the EC50 value of UK14,304 to 0.68+/
      0.01 microM. The addition of amiloride (100 microM), a Na+ channel blocker, to
      the fluid bathing the apical side was found not to change the effect of dopamine
      on Isc. 5-(N-ethyl-N-isopropyl)-amiloride (10 microM), a selective Na+/H+
      exchanger inhibitor, partially antagonised the effect produced by 100 microM of
      dopamine. The addition of ouabain (1 mM) to the fluid bathing the basal side,
      antagonised the effect produced by 50 and 100 microM of dopamine. In contrast,
      frusemide (1 mM) completely abolished the effect of all concentrations of
      dopamine. Forskolin (10 microM) and N6,2'-O-dibutyryl cyclic AMP (1 mM) added to
      both the apical and serosal sides completely abolished the effect of dopamine on
      Isc. It is concluded that the dopamine antisecretory effects in the jejunum of
      adult rats are mediated through alpha2-adrenoceptors. This effect is sensitive to
      increases in intracellular cyclic AMP and is primarily dependent on the basal
      Na+,K+,2Cl- -co-transport mechanism.

PMID- 9761425
TI  - Effects of LEX032, a novel recombinant serine protease inhibitor, on N(G)-nitro-L
      arginine methyl ester induced leukocyte-endothelial cell interactions.
AB  - We studied the effects of LEX032, a novel serine protease inhibitor, on N(G)
      nitro-L-arginine methyl ester (L-NAME) induced leukocyte-endothelium interactions
      in vivo, utilizing intravital microscopy of the rat mesentery. Superfusion of the
      rat mesentery with 50 microM L-NAME, a nitric oxide (NO) inhibitor, for 90 min
      resulted in a significant and time-dependent increase in leukocyte rolling,
      leukocyte adherence, and transmigration of leukocytes, compared to control rats
      superfused with Krebs-Henseleit (K-H) solution. However, systemic administration
      of LEX032 (15 mg/kg bolus injection followed by a 15 mg/kg per hour infusion) to
      L-NAME superfused rats significantly attenuated leukocyte rolling and adherence
      along the venular endothelium of the rat mesentery, and also inhibited
      transmigration of leukocytes through the microvascular endothelial wall.
      Moreover, no significant changes were observed in mean arterial blood pressure or
      local venular shear rates following systemic administration of LEX032. Our data
      demonstrate that systemic inhibition of serine proteases by LEX032 reduces
      enhanced leukocyte-endothelium interactions provoked by inhibition of NO
      synthesis. These results also explain some of the beneficial effects exerted by
      serine protease inhibitors in ischemia-reperfusion and other inflammatory states.

PMID- 9761426
TI  - Cyclooxygenase 2 expression by endothelin-1-stimulated mouse resident peritoneal
      macrophages in vitro.
AB  - Macrophages have been shown to produce endothelin and to play a role in the
      pathogenesis of neural damage after cerebral ischemia or vasospasm after
      subarachnoid hemorrhage. Cyclooxygenase 2 is induced during inflammation
      following brain insult and participates in inflammation-mediated neurotoxicity.
      However, it has not yet been established how endothelin-1 acts on cyclooxygenase
      2 expression in macrophages. In the present study, we examined the effects of
      endothelin-1 on cyclooxygenase 2 expression and prostaglandin E2 production, and
      the effects of endothelin ET(A) and ET(B) receptor antagonists. Stimulation by
      endothelin-1 ranging from 10(-11) to 10(-9) M time and dose dependently increased
      the production of prostaglandin E2 and the expression of cyclooxygenase 2 protein
      without changing that of cyclooxygenase 1 protein, an effect which was inhibited
      by dexamethasone, nonsteroidal anti-inflammatory drugs and the selective
      endothelin ET(B) receptor antagonist, BQ788 (N-cis-2,6-dimethylpiperidinocarbonyl
      L-gamma-methyl-leucyl-D-L-me thoxycarbonyl-tryptophanyl-D-norleucine). The
      selective endothelin ET(A) receptor antagonist, BQ123 [cyclo (D-Trp-D-Asp-Pro-D
      Val-Leu)] also inhibited these reactions, but its potency was less than that of
      the selective endothelin ET(B) receptor antagonist. Endothelin ET(A) and ET(B)
      receptor antagonists had no effects on cyclooxygenase 2 protein expression and
      prostaglandin E2 production in lipopolysaccharide-stimulated macrophages. We
      conclude that endothelin-1 increases cyclooxygenase 2 protein expression and
      prostaglandin E2 production via mainly endothelin ET(B) receptors and partly
      endothelin ET(A) receptors in macrophages; however, lipopolysaccharide increases
      both cyclooxygenase 2 protein expression and prostaglandin E2 production in
      pacrophages without involving endothelin ET(A) or ET(B) receptor-mediated
      processes.

PMID- 9761428
TI  - Medium change amplifies mitogen-activated protein kinase-mediated prostaglandin
      E2 synthesis in Swiss 3T3 fibroblasts.
AB  - In Swiss 3T3 fibroblasts, changing the culture medium prior to stimulation
      resulted in an augmentation of bradykinin-induced prostaglandin E2 synthesis. The
      augmentation depended on the duration of the exposure to the fresh medium, with a
      maximum effect at 1 h. Fetal calf serum in the fresh medium was essential for
      augmented prostaglandin E2 synthesis. The medium change slightly augmented the
      bradykinin-induced increase in intracellular free Ca2+ concentration and
      phosphoinositide hydrolysis with a different time course from that for
      prostaglandin E2 synthesis. 4',5,7-Trihydroxyisoflavone (genistein) and 3,4
      dihydroxybenzylidene-malononitrile (tyrphostin 23), inhibitors of tyrosine
      kinases, and 2'-amino-3'-methoxyflavone (PD98059), an inhibitor of mitogen
      activated protein kinase (MAPK) kinase, attenuated the increase in prostaglandin
      E2 synthesis. Bradykinin caused phosphorylation of cytosolic phospholipase A2 and
      p42/p44 MAPK, which was augmented by the medium change. From the results, it is
      concluded that activation of MAPK and cytosolic phospholipase A2 is involved in
      the augmentation of prostaglandin E2 synthesis produced by the medium change.

PMID- 9761427
TI  - Dialdehyde sesquiterpenes and other terpenoids as vanilloids.
AB  - Selected naturally occurring unsaturated dialdehyde sesquiterpenes and related
      bioactive terpenoids were assayed for vanilloid-like activity. Out of the 25
      compounds tested, eight inhibited completely the specific binding of
      [3H]resiniferatoxin by rat spinal cord membranes: binding affinities ranged from
      0.6 microM for cinnamodial to 19.0 microM for hebelomic acid F. These values were
      comparable to the binding affinity of capsaicin (2.7 microM). With the exception
      of four ligands, compounds that inhibited resiniferatoxin binding to rat spinal
      cord membranes were also pungent on the human tongue where they showed cross
      tachyphylaxis with capsaicin. As expected from their reactive nature, these
      compounds possess additional sites of action, as reflected in the complex
      behavior of the stimulation of calcium influx by cinnamodial and cinnamosmolide
      at high concentrations. This observation might explain the unexpectedly weak
      membrane depolarization by cinnamodial compared to capsaicin. We conclude that a
      range of sesquiterpene dialdehydes and related terpenoids, both pungent and non
      pungent, may function as vanilloids. These compounds may represent a new chemical
      lead for the development of vanilloid drugs, structurally unrelated to either
      capsaicin or resiniferatoxin.

PMID- 9761429
TI  - Cardiac surgery beyond the Urals.

PMID- 9761430
TI  - Pulmonary artery stenosis after systemic-to-pulmonary shunt operations.
AB  - OBJECTIVE: Systemic-to-pulmonary shunt operations are still required for
      palliation of certain congenital heart defects. The aim of this study was to
      analyze the incidence and etiology of the development of pulmonary artery
      stenosis after these procedures. METHODS AND RESULTS: Pre- and post-operative
      angiograms of 59 patients who underwent 54 peripheral and 12 central shunt
      operations were analyzed retrospectively. Patients without prior cardiovascular
      interventions (group I, n = 47) were differentiated from patients with prior
      interventions (group II, n = 12). In group I, all peripheral shunts were inserted
      contralaterally to the ductus arteriosus. Follow-up for all patients was 1.8
      years (4 days-7.8 years). Pulmonary artery stenosis was diagnosed in 12/59
      patients (20.3%, group I 12/47; group II 0) after a time interval of 4 days up to
      5.3 years and only after Blalock-Taussig shunts (one classical, 11 modified)
      (12/40 = 30%). The stenoses were located ipsilaterally to the shunt in 7/12 and
      contralaterally in 5/12. Statistical analysis did not show any impact of age,
      weight, sex, shunt type or size, pulmonary artery diameters, Nakata and McGoon
      indices and prior interventions on the development of pulmonary artery stenosis.
      However, a patent ductus arteriosus and administration of Prostaglandin E1 had a
      significant impact on the development of pulmonary artery stenosis on the side of
      the ductus arteriosus. CONCLUSION: Pulmonary artery stenosis is not a rare event
      after systemic-to-pulmonary shunt operations. A patent ductus arteriosus with or
      without administration of Prostaglandin E1 is related to pulmonary artery
      stenosis on the side of the ductus arteriosus. Pulmonary artery stenosis on the
      side of a peripheral shunt may be caused by inappropriate surgical technique,
      increased intimal proliferation, or pulmonary artery kinking. Treatment depends
      on severity of cyanosis and on further surgical plans.

PMID- 9761431
TI  - Results of primary and two-stage repair of interrupted aortic arch.
AB  - OBJECTIVE: Early results of primary and two-stage repair of interrupted aortic
      arch have improved. Experience with different surgical approaches should be
      analysed and compared. METHODS: Forty neonates and infants with interrupted
      aortic arch underwent primary repair (19 patients) or palliative operation (21
      patients). Twenty (50%) patients were followed-up for 5.1+/-4.3 years. All
      patients were regularly examined with the aim of determining clinical
      development, presence of residual lesions or complications and need for re
      intervention. Aortic arch and the left ventricular outflow tract growth were
      assessed by echocardiographic examination. Data from hospital and outpatient
      department records were analysed. RESULTS: The early mortality was 61.9% after
      palliative operations and 36.8% after the primary repair. Presence of
      complications (P < 0.001), earlier year of surgery (P < 0.01), bad clinical
      condition and acidosis (P < 0.05) represented statistically significant risk
      factors for death in the whole series. In seven (87.5%) out of eight early
      survivors, after the initial palliative operation, closure of ventricular septal
      defect and debanding were done, and in three (37.5%) patients, re-operation for
      aortic arch obstruction was also required. Out of 12 patients, after the primary
      repair, one required early re-operation for persistent left ventricular outflow
      tract obstruction and two needed late re-intervention for left bronchus
      obstruction. In three (25%) patients, after the primary repair, left ventricular
      outflow tract obstruction with a maximal systolic pressure gradient higher than
      30 mmHg developed. At present, all 20 early survivors are alive. Five patients,
      after palliative operation, are in NYHA class 1, but in three patients, who are
      in class III or IV, the outcome is influenced by severe complications. All
      patients after the primary repair are in class I or II. CONCLUSIONS: Our
      experience confirmed better results after the primary repair of interrupted
      aortic arch, which was associated with lower mortality, prevalence of severe
      complications and need for re-intervention. Higher prevalence of subaortic
      stenosis after primary repair could be explained by patient selection early in
      our experience. We recommend the primary repair of interrupted aortic arch and
      associated heart lesions in neonates, however, in unfavourable conditions an
      individualised surgical approach with initial palliative surgery should be
      considered.

PMID- 9761433
TI  - Contribution of the interventricular septum to maximal right ventricular
      function.
AB  - OBJECTIVE: Maximal right ventricular (RV) function is influenced by left heart
      hemodynamics, possibly mediated by the interventricular scpturn (IVS). We
      examined the potential contribution of the IVS function to right heart function.
      METHODS: In 12 canine isovolumic right heart preparations, incremental volumes
      were introduced into a high compliance RV balloon until RV failure occurred.
      Maximal RV developed pressure (RVDP) and maximal positive RV dP/dt were
      determined with a working IVS at a constant left ventricular (LV) output of 2
      l/min and at a constant mean arterial pressure of 80 mmHg. Thereafter the IVS was
      thermally inactivated, and measurements were repeated using the same protocol.
      RESULTS: At constant arterial pressure and constant LV output, thermal
      inactivation of the IVS led to a significant decrease in maximal RVDP
      (inactivated vs. working IVS: 36.1+/-9.8 vs. 56.8+/-16.2 mmHg, respectively, P <
      0.001), and RV dP/dt (inactivated vs. working IVS: 720+/-220 vs. 1350+/-190
      mmHg/s, respectively, P < 0.001). CONCLUSIONS: These results suggest that the
      functional status of the IVS is a major determinant of maximal RV function. At
      constant LV conditions and arterial pressure, an inactivated IVS leads to a
      significant decrease in maximal RVDP and RV dP/dt under the conditions of this
      study.

PMID- 9761432
TI  - Myocardial protection by pressure- and volume-controlled continuous hypothermic
      coronary perfusion in combination with Esmolol and nitroglycerine for correction
      of congenital heart defects in pediatric risk patients.
AB  - OBJECTIVE: This study assesses the technical applicability and the clinical value
      of the continuous coronary perfusion with oxygenated blood as a method for
      myocardial protection used for congenital heart surgery in pediatric risk
      patients. METHODS: Thirty non-consecutive pediatric risk patients aged from 1
      month to 16 years (mean 3.9 years; 11/30 patients aged <6 months) underwent open
      heart procedures on the beating heart for simple and complex cardiac
      malformations using a self designed perfusion system with pressure- and volume
      controlled continuous hypothermic coronary perfusion (PVC-CONTHY-CAP) in
      combination with ultra-short beta1-receptor blockade (Esmolol) and nitroglycerine
      for myocardial protection. The following procedures were done: VSD patch closure
      (n = 6), repair of total a-v canal with 'double patch' (n = 4), total repair of
      tetralogy of Fallot (n = 7), correction of truncus arteriosus communis type IV (n
      = 1), mitral valve reconstruction (n = 4), total cavo-pulmonary connection (n =
      4), and Rastelli procedure (n = 4). RESULTS: The mean cardio-pulmonary bypass
      time was 131.5 min (range: 44-245 min), the mean coronary perfusion time: 90.1
      min (range: 13-202 min). The weaning off extracorporeal circulation was
      uneventful in all patients, in 21 patients with low-dose and in nine patients
      with moderate catecholamine support: the mean weaning time was 25 min (range: 7
      58 min). The post-operative mean peak creatine kinase (CK-MB) value was 58 U/l,
      (range: 14-202 U/l). The mean ICU stay in the cardiac surgery unit was 2.9 days,
      (range: 1-10 days). The mean post-operative mechanical ventilatory support was 2
      days (range: 6 h-9 days). Six patients developed thrombocytopenia with values <40
      tsd/microl, four patients renal dysfunction, two patients ascites, five patients
      heart rhythm disturbances, one patient neurological deficits. In three patients
      (VSD closure: n = 2; age: 1 and 2 months; total a-v-canal: n = 1; age: 3 months)
      re-do procedures for significant intraventricular shunt had to be done, in one
      patient implantation of a permanent pacemaker system was necessary. One patient
      died due to multiple organ failure after uneventful surgery (total cavo-pulmonary
      connection for single ventricle). CONCLUSIONS: PVC-CONTHY-CAP can be successfully
      used for repair of simple and complex congenital cardiac malformations. However,
      in children less than 3 months of age, the transatrial repair of intraventricular
      defects is technically much more demanding and challenging than under
      conventional cardioplegic arrest and is possibly accompanied by an increased
      incidence of residual or recurring intraventricular shunts.

PMID- 9761434
TI  - Advantage of post-operative oral administration of UFT (tegafur and uracil) for
      completely resected p-stage I-IIIa non-small cell lung cancer (NSCLC).
AB  - OBJECTIVE: Although adjuvant therapy after surgery for non-small cell lung cancer
      (NSCLC) has been reported to be ineffective, it has been recently reported in
      prospective randomised studies conducted by two different groups in Japan that
      oral administration of a 5-fluorouracil (5-FU) derivative drug, UFT (a
      combination drug of tegafur and uracil) can improve the post-operative survival
      [The Study Group of Adjuvant Chemotherapy for Lung Cancer (Chubu, Japan). A
      randomized trial of postoperative adjuvant chemotherapy in non-small cell lung
      cancer (the second cooperative study). Eu J Surg Oncol 1995;21:69-77; Wada, H.,
      Hitomi, S., Teramatsu, T, West Japan Study Group for Lung Cancer Surgery.
      Adjuvant chemotherapy after complete resection in non-small-cell lung cancer. J
      Clin Oncol 1996;14:1048-1054]. To examine the efficacy of UFT as post-operative
      adjuvant therapy, a retrospective study was performed. METHODS: A total of 655
      consecutive patients who underwent complete tumor resection for pathologic stage
      I-IIIa, NSCLC at the Department of Thoracic Surgery, Chest Disease Research
      Institute, Kyoto University between 1976 and 1992 were retrospectively reviewed.
      As post-operative adjuvant therapy, UFT was administrated to 98 patients (UFT
      group), and was not administered to the other 557 patients (Control group).
      RESULTS: The 5-year survival rate of the UFT group was 76.5%, which was
      significantly better than that of the Control group (5-year survival rate: 58.6%,
      P = 0.005). Stratified with pathologic stage, the efficacy of UFT was seen in the
      p-stage I disease (5-year survival rate: 88.6% for the UFT group, 72.0% for the
      Control group, P = 0.013) and in the p-stage IIIa, pN2 disease (5-year survival
      rate: 54.3% for the UFT group, 37.5% for the Control group, P = 0.037).
      Multivariate analysis of the prognostic factors also revealed the efficacy of UFT
      (P = 0.004, 95% confidence interval of relative risk: 0.325-0.840). Post
      operative intravenous chemotherapy or radiation therapy did not prove to be
      significant factors affecting the prognosis. CONCLUSIONS: Efficacy of oral
      administration of UFT as post-operative adjuvant therapy for completely resected
      NSCLC was proposed. To confirm the efficacy, a prospective randomized study for a
      more homogenous patient group is needed.

PMID- 9761436
TI  - Repeat mediastinoscopy in the staging of lung cancer.
AB  - OBJECTIVE: Despite technical difficulties due to mediastinal fibrosis, repeat
      mediastinoscopy can be a valuable tool in the restaging of lung cancer. It
      provides essential pathological information on mediastinal invasion when
      selecting patients for surgical resection after induction chemotherapy in stage
      IIIa disease. The aim of our study was to evaluate the feasibility, sensitivity
      and accuracy of repeat mediastinoscopy. METHODS: From 1994 to 1997 we performed a
      repeat mediastinoscopy in 15 patients (13 men, two women) with bronchogenic
      carcinoma. Their age ranged from 49 to 75 years. (mean 64.7). Seven patients had
      induction chemotherapy for a non-small cell bronchogenic carcinoma with positive
      N2 nodes on mediastinoscopy. Four patients had a second primary contralateral
      lung cancer, one had a locoregional recurrence of bronchogenic carcinoma. The
      other three had a first mediastinoscopy for other reasons than lung cancer,
      repeat mediastinoscopy being performed for staging of malignant disease. RESULTS:
      In all 15 patients it was possible to perform a complete repeat mediastinoscopy.
      In one patient repeat mediastinoscopy turned out to be false negative, so, in our
      series, sensitivity was 87.5%, specificity 100% and accuracy 93.7%. CONCLUSION:
      Previous mediastinoscopy is no contraindication for a repeat one. Repeat
      mediastinoscopy offers valuable pathological information in restaging of lung
      cancer.

PMID- 9761435
TI  - CT-guided methylene-blue labelling before thoracoscopic resection of pulmonary
      nodules.
AB  - OBJECTIVE: Evaluation of the efficiency of our technique of methylene-blue
      labelling of pulmonary nodules to facilitate thoracoscopic recognition and
      excision. DESIGN: Patients with a peripheral pulmonary nodule smaller than 2.5 cm
      and not in contact with the visceral pleura were included. Under
      tomodensitometric guidance, the nodules were labelled with methylene-blue within
      hours before thoracoscopic wedge resection. If frozen section revealed a primary
      bronchial carcinoma, thoracotomy and classical resection were performed during
      the same anesthesia. RESULTS: Between July 1992 and August 1996, 54 nodules were
      removed in 51 patients. Labelling was performed between 75 and 270 min before
      surgery and was complicated in 13 patients (25.4%) by a small pneumothorax
      without any clinical consequence. Labelling allowed successful thoracoscopic
      recognition of 50 nodules (92%) and thoracoscopic wedge resection was possible in
      all but one cases (91%). Five patients (9%) required thoracotomy. Histology
      showed a benign lesion in 22 cases, a primary lung carcinoma in 17 and a
      metastases in 15. Twenty of the 22 benign nodules (91%) were removed without
      thoracotomy. According to the protocol, 13 patients with a primary lung tumour
      underwent lobectomy during the same session. There was no mortality nor morbidity
      amongst patients who had thoracoscopy only. CONCLUSIONS: Our technique of
      labelling peripheral pulmonary nodules with methylene-blue is very effective and
      is not associated with any relevant complication. Thoracoscopic excision and
      diagnosis is possible in more than 90% of the cases. We therefore recommend this
      simple, low-cost and reliable technique for nodules not in contact with the
      visceral pleura before thoracoscopic wedge resection.

PMID- 9761437
TI  - Less invasive approaches for closed mitral commissurotomy.
AB  - OBJECTIVE: Recently, closed mitral commissurotomy (CMC) has been reexplored due
      to the concepts of less invasive valvular surgery. The feasibility of closed
      mitral commissurotomy via port access or limited thoracotomy by aid
      transesophageal echocardiography (TEE) was investigated in this clinical study.
      METHODS: Between August 1996 and April 1998, 42 patients (32 women, ten men with
      a mean age of 36.2+/-7.8 years) underwent less invasive CMC at the Kosuyolu Heart
      and Research Hospital. CMC procedure were done through a limited (12-16 cm)
      thoracotomy incision in 23 patients, a very limited or mini thoracotomy incision
      (7-8 cm) in 11 patients and port access by aid TEE in eight patients.
      Preoperative mean mitral valve area was calculated as 1.19+/-0.13 cm2 and mean
      mitral valve gradient was measured as 14.8+/-3.2 mmHg. TEE provided information
      about the mitral valve anatomy and functions during the procedure in all
      patients. RESULTS: Commissurotomy was successfully performed in all patients. In
      eight patients, a Tubbs dilator was inserted via port access at the 6th
      intercostal space from a 3-cm incision. Incision by guidance of TEE and CMC could
      be performed without thoracotomy in five patients. In three patients of the port
      access group, a very limited thoracotomy was required to perform CMC by digital
      guidance. Postoperative mean MVA was 2.37+/-0.29 cm2, minimal mitral gradient was
      5.3+/-1.7 mmHg. In eleven patients, minimal mitral regurgitation was observed.
      The operations and postoperative period were free of complications in all
      patients. Following an average 12+/-2.8 h intensive care unit period, all
      patients were discharged after an average of 3.4+/-0.8 days of hospitalization.
      CONCLUSION: Limited thoracotomy has less detrimental structural effects in
      patients. Port access by aid TEE approach to CMC may offer less invasiveness,
      lower cost effectiveness and be an alternative to percutaneous balloon mitral
      valvotomy.

PMID- 9761438
TI  - Tissue engineering of heart valves--human endothelial cell seeding of detergent
      acellularized porcine valves.
AB  - OBJECTIVE: Tissue engineering of heart valves represents a new experimental
      concept to improve current modes of therapy in valvular heart disease. Drawbacks
      of glutaraldehyde fixed tissue valves or mechanical valves include the short
      durability or the need for life-long anticoagulation, respectively. Both have in
      common the inability to grow, which makes valvular heart disease especially
      problematic in children. The aim of this study was to develop a new methodology
      for a tissue engineered heart valve combining human cells and a xenogenic
      acellularized matrix. METHODS: Porcine aortic valves were acellularized by
      deterging cell extraction using Triton without tanning. Endothelial cells were
      isolated in parallel from human saphenous veins and expanded in vitro. Specimens
      of the surface of the acellular matrix were seeded with endothelial cells.
      Analysis of acellularity was performed by light microscopy and scanning electron
      microscopy. Cell viability following seeding was assayed by fluorescence staining
      of viable cells. RESULTS: The acellularization procedure resulted in an almost
      complete removal of the original cells while the 3D matrix was loosened at
      interfibrillar zones. However the 3D arrangement of the matrix fibers was grossly
      maintained. The porcine matrix could be seeded with in vitro expanded human
      endothelial cells and was maintained in culture for up to 3 days to document the
      formation of confluent cultures. CONCLUSIONS: Porcine aortic valves can be almost
      completely acellularized by a non-tanning detergent extraction procedure. The
      xenogenic matrix was reseeded with human endothelial cells. This approach may
      eventually lead to the engineering of tissue heart valves repopulated with the
      patients own autologous cells.

PMID- 9761439
TI  - The effects of mechanical cardiac stabilization on left ventricular performance.
AB  - OBJECTIVE: Mechanical cardiac stabilization is beneficial for precise coronary
      anastomoses on the beating heart. However, the effect of mechanical cardiac
      stabilization on hemodynamics, left ventricular performance, and the degree of
      injury to underlying tissue are uncertain. METHODS: Twelve swine (20-30 kg)
      underwent median sternotomy and a mechanical stabilizing device (United States
      Surgical, Norwalk, CT) was positioned astride a segment of left anterior
      descending coronary artery (LAD). Coronary blood flow was measured by Doppler.
      Sonomicrometry crystals were placed distal to the stabilizer in a region of
      myocardium subtended by the LAD, and a left ventricular micromanometer was
      inserted. Regional myocardial function was determined using the preload
      recruitable stroke work (PRSW) relationship. Data were acquired at three time
      points: 20 min before (PRE) and after placing the stabilizer (EXPT); and 20 min
      after removing the stabilizer (POST). Tissue subjacent to the stabilizer was then
      biopsied. Means +/- standard deviation are reported. RESULTS: The mechanical
      stabilizer caused a decrease in cardiac output from 4.2+/-1.5 to 3.6+/-1.3 l/min
      (P < 0.05), which returned to baseline values after its removal. Regional
      myocardial function (percent systolic shortening and MW and x-intercept of the
      PRSW relationship) was unchanged. Blood pressure, heart rate, and LAD blood flow
      remained constant. Histologic findings included a layer of myocyte necrosis less
      than 1 mm in depth immediately beneath the stabilizer. CONCLUSIONS: These data
      demonstrate that mechanical stabilization of the LAD may temporarily decrease
      cardiac output. This is not attributed to impaired contractility or ischemia, but
      is secondary to direct ventricular compression with reduced stroke volume. Injury
      to underlying tissue is negligible.

PMID- 9761440
TI  - Soluble adhesion molecules in reperfusion during coronary bypass grafting.
AB  - OBJECTIVE: Adhesion of activated leukocytes to the endothelial cells as a result
      of myocardial ischaemia/reperfusion during open chest coronary artery surgery has
      been shown to be involved in the development of tissue damage. Activated
      leukocytes adhere to endothelium via adhesion molecules expressed by both cell
      types, resulting in the impairment of coronary capillary flow. Upon cell
      activation, adhesion proteins may be released in the soluble form to circulating
      blood. The purpose of our study was to verify whether myocardial
      ischaemia/reperfusion occurring during coronary artery bypass grafting results in
      release of the soluble adhesion molecules VCAM-1, ICAM-1, E-selectin and L
      selectin into the circulation. METHODS: Plasma levels of the soluble adhesion
      molecules were measured in vein, arterial and coronary sinus blood samples taken
      from 15 patients undergoing coronary artery bypass grafting (CABG). Blood samples
      for estimations were collected during the procedure: before aorta cross-clamping,
      at the beginning of reperfusion and 30 min after reperfusion. Soluble adhesion
      molecules levels were measured by standard ELISA assays. RESULTS: Mean plasma
      levels of soluble VCAM-1 in arterial samples increased significantly at the
      beginning of reperfusion and 30 min after reperfusion. In contrast, soluble L
      selectin plasma levels in arterial samples remained unchanged. In coronary sinus
      samples, levels of soluble ICAM-1 significantly increased 30 min after
      reperfusion. Moreover, in coronary sinus samples collected 30 min after
      reperfusion, soluble ICAM-1 levels were significantly higher than in arterial
      samples obtained at the same time. The mean concentration of soluble E-selectin
      in samples obtained from coronary sinus decreased significantly 30 min after
      reperfusion. Moreover, plasma levels of soluble E-selectin in coronary sinus
      samples obtained 30 min after reperfusion were significantly decreased compared
      with these observed in arterial samples collected at the same time. CONCLUSIONS:
      The reperfusion of ischaemic myocardium during CABG results in a significant
      increase in plasma levels of the soluble endothelial adhesion molecules VCAM-1
      and ICAM-1 and significant decrease in soluble E-selectin plasma levels. L
      selectin plasma levels during CABG procedure remain unchanged. We propose that
      the increased plasma concentrations of soluble VCAM-1 and ICAM-1 are a result of
      endothelial cell activation during ischaemia/reperfusion following bypass
      surgery.

PMID- 9761442
TI  - Preconditioning of the latissimus dorsi muscle in cardiomyoplasty: vascular delay
      or chronic electrical stimulation.
AB  - OBJECTIVES: In standard single stage cardiomyoplasty (CMP), the latissimus dorsi
      muscle (LDM) is not preconditioned prior to surgery. We hypothesized that
      latissimus dorsi preconditioning by vascular delay or by chronic electrical
      stimulation would result in an improved LV hemodynamic function early (14 days)
      after CMP. METHODS: Mongrel dogs had preconditioning of the latissimus dorsi by a
      vascular delay procedure followed by CMP 14-18 days later (group I VD). Dogs in
      group II underwent 4 weeks of chronic stimulation (CS) of the latissimus dorsi (2
      V/30 Hz, six bursts/min) followed by CMP. The latissimus dorsi muscle was fully
      stimulated from 48 h after cardiomyoplasty in both groups (2 V/30 Hz, three
      bursts/min). Two weeks after myoplasty, injecting 2.0-3.0 x 10(5) 90 microm latex
      microspheres in the left main coronary artery induced global cardiac dysfunction.
      Hemodynamic function was then evaluated for latissimus dorsi muscle assisted (S)
      beats and non-stimulated beats (NS) in each group by measuring peak systolic
      aortic pressure (AOP), left ventricular pressure (LVP) and end diastolic pressure
      (LVEDP), and by calculating maximum and minimum dP/dt. RESULTS: Dogs with
      vascular delay of the latissimus dorsi showed a marked increase for all
      hemodynamic indices (AOP: 23.9+/-2.5%, LVP: 23.5+/-2.2%, max dP/dt: 49.4+/-3.3%)
      for LDM assisted (S) beats compared to non-stimulated beats (P < 0.001). Animals
      with chronic electrical training did not demonstrate a significant increase in
      any hemodynamic parameter with LDM stimulation. CONCLUSION: Preconditioning the
      LDM may play an important role in providing early cardiac assistance in CMP.
      Preconditioning the LDM with vascular delay resulted in improving performance of
      the LDM with consistent increases in LV hemodynamics. This was not observed after
      preconditioning with chronic electrical stimulation. Vascular delay of the
      latissimus dorsi can significantly improve muscle performance in CMP and could
      provide hemodynamic assistance early after surgery.

PMID- 9761441
TI  - Discrete subaortic stenosis: an acquired heart disease.
AB  - OBJECTIVE: To determine the anatomic variables in the left ventricular outflow
      tract in patients with subaortic stenosis. METHODS: Between 1982 and 1996, 36
      patients were operated on with the 'discrete' form of subaortic stenosis (DSS).
      The mean time of follow up was 7.4 years with a range of 4 months-14 years. There
      were 25 male and 11 female patients. Mean age at operation was 7.1 years with a
      range of 9 months-47 years. RESULTS: At the time of surgery, the mitral valve
      apparatus and interventricular septum were found to be rotated 60-90 degrees in a
      counterclockwise fashion with anterior displacement into the left ventricular
      outflow tract in 30 (83%) patients. Subaortic ridge resection with a deep septal
      myectomy was performed in 32 patients and the remaining four patients had
      subaortic ridge resection alone. The reoperation free rate at 5 and 10 years were
      74+/-9% and 60+/-12%, respectively. Reoperations for recurrent disease were
      performed in 10 (27.7%) patients. No operative or late follow up deaths were
      encountered. CONCLUSION: We conclude that DSS is an acquired disease due to a pre
      existing anatomic alteration in the mitral valve apparatus and interventricular
      septum. In addition, recurrence rates are high and physicians should not be
      mislead by the benign nomenclature its name implies.

PMID- 9761443
TI  - Does bronchial artery revascularization influence results concerning
      bronchiolitis obliterans syndrome and/or obliterative bronchiolitis after lung
      transplantation?
AB  - OBJECTIVE: To study the frequency of histological obliterative bronchiolitis and
      clinical bronchiolitis obliterans syndrome after en bloc double lung
      transplantation with bronchial artery revascularization and bilateral lung
      transplantation without bronchial artery revascularization. METHODS: Primary en
      bloc double lung transplantation with bronchial artery revascularization using
      the internal mammary artery as conduit was performed in 62 patients. The
      frequencies of obliterative bronchiolitis and bronchiolitis obliterans syndrome
      have been established from transbronchial biopsies and lung function
      measurements. Results have been analyzed in relation to the arteriographic
      success of bronchial artery revascularization and have been compared to results
      from Stanford University, obtained through personal communications. RESULTS:
      Survival after 1, 2, 3, 4 and 5 years was 85, 81, 69, 69, and 69%, respectively.
      Fifteen patients developed bronchiolitis obliterans syndrome while seven
      developed obliterative bronchiolitis. Survival was superior for patients with
      bronchial artery revascularization classified as complete or incomplete bilateral
      versus incomplete hemilateral, incomplete poor or failed (P = 0.016, log-rank
      test). For patients surviving > or = 3 months post-transplant, the post-operative
      baseline FEV1 was lower for patients who later developed bronchiolitis obliterans
      syndrome compared to patients who did not (P = 0.007). The development of
      bronchiolitis obliterans syndrome and obliterative bronchiolitis were both
      correlated to observation time post-transplant but not to the number of
      rejections or infections when corrected for observation time. CONCLUSIONS: In a
      subgroup of lung transplant patients, a process in the transplanted lungs,
      eventually leading to bronchiolitis obliterans syndrome diagnosis, seems to start
      in the donor during the transplantation and/or in the early post-operative cause.
      A comparison with results after bilateral lung transplantation without bronchial
      artery revascularization suggests that good direct bronchial artery
      revascularization may postpone the onset of bronchiolitis obliterans syndrome and
      obliterative bronchiolitis. The positive trend motivates further use of direct
      bronchial artery revascularization in lung transplantation.

PMID- 9761444
TI  - Warm ischemic time tolerance after ventilated non-heart-beating lung donation in
      piglets.
AB  - OBJECTIVE: The availability of lungs for transplantation could be ameliorated
      with the use of organs retrieved from ventilated non-heart-beating donors
      (VNHBD). The aim of this work is to determine the limit to tolerable in situ warm
      ischemia time (WIT) for lung grafts after circulation is stopped. METHODS: Twenty
      piglets underwent left lung allotransplantation. Animals were randomly allocated
      based on the donor's status before lung harvesting into the following study
      groups: Sham (n = 5), Heart-beating donors-non-warm ischemia; I-30 (n = 5), I-60
      (n = 5) and I-90 (n = 5), VNHBD-WIT of 30, 60 and 90 min, respectively. Right
      pulmonary artery and bronchus were permanently occluded one hour after
      transplantation. Assessment of pulmonary function was monitored hourly by
      hemodynamic, oxygenation and pulmonary mechanic measurements during a period of 6
      h after reperfusion. Lung grafts were weighed pre- and post-transplantation.
      RESULTS: Cold ischemic time was similar for all groups, and averaged 80.1+/-2.7
      min. Final mean lung weight was significantly greater in VNHBD (92.5+/-3.1 g vs.
      Sham values 75.6+/-2.4 g, P < 0.01). After right lung exclusion, hemodynamic
      changes consisted of a sustained increase in pulmonary vascular resistance and a
      reduction in cardiac output. Lung mechanics also modified, with a rise in airway
      resistance and a fall in compliance. CONCLUSIONS: Post-transplantation lung graft
      function from VNHBD with up to 90 min of WIT, is equivalent to those achieved by
      grafts harvested after heart-beating donation. This method may be a promising
      strategy of increasing the pulmonary donor pool.

PMID- 9761445
TI  - Aortic valve stenosis causing a left-to-right shunt in persistent left superior
      vena cava communicating with the left atrium.
AB  - This study demonstrated a rare anomaly of a persistent left superior vena cava
      draining into the left atrium in a patient with developing left-to-right shunt
      caused by bicuspid aortic stenosis. The venous system, including the coronary
      sinus, was otherwise normal. We believe that, in this anatomic situation, a
      marked increase in left ventricular impedance caused a moderate left-to-right
      shunt from the left atrium into the left innominate vein. At operation, the
      aortic valve was replaced with a mechanical prosthesis and the anomalous vein was
      ligated. The convalescence was uneventful.

PMID- 9761446
TI  - Open surgery for removal of a failing Gianturco stent with reversed sleeve
      resection of the right middle and lower lobes.
AB  - Although the use of a metallic stent in the treatment of benign tracheobronchial
      stenosis has been reported as a useful and safe technique, the incorporation of
      wire stents into the airway may be irreversible and is associated with problems.
      The authors' experience in a patient with incorrectly positioned metallic stent
      in the right main bronchus, which was successfully treated with bronchial sleeve
      resection, is presented.

PMID- 9761447
TI  - Stent implantation for post-Mustard systemic venous obstruction.
AB  - In this paper, we report on the use of stents in the treatment of late-onset post
      Mustard systemic venous obstruction in three patients with clinical signs of
      obstructive caval syndrome. After unsuccessful balloon dilation, Palmaz-Schatz
      stents were implanted at the veno-atrial junction. Further dilation has been
      achieved using high-pressure balloons. Vessel diameter increased from 4.4+/-1.8
      to 13+/-1.7 mm (P < 0.05) and the trans-stenotic pressure gradient dropped from
      8+/-6 to 0 mmHg (P < 0.01), with clinical improvement. After 26+/-4 months of non
      invasive follow-up, no signs of recurrent stenosis were observed. Stent
      implantation is effective in the treatment of systemic venous obstruction after
      Mustard operation.

PMID- 9761448
TI  - A multivesicular cardiac hydatid cyst with hepatic involvement.
AB  - Cardiac hydatid cyst is an uncommon lesion, mostly caused by Echinococcus
      granulosus. Occurrence of the disease in man appears to be limited geographically
      to areas where close and continuous contact exists between domesticated
      carnivores such as dogs and ungulates such as cattle and sheep. Generally cardiac
      hydatid cysts are univesicular. Here we report our clinical and surgical
      experience of treatment in a case of a multivesicular cardiac hydatid cyst with
      hepatic involvement.

PMID- 9761449
TI  - Surgical approach for cardiac surgery in a patient with tracheostoma.
AB  - The thoracic approach for cardiac surgery in a patient with a tracheostoma can
      result in difficult problems, such as mediastinitis, stoma necrosis or inadequate
      operative exposure. We present a distinct approach consisting of an incision at
      the second intercostal space, transverse sternum transection and longitudinal
      median sternotomy to the xiphoid process, performed for coronary artery bypass
      grafting and aortic valve replacement, in a patient with previous tracheotomy.
      This approach permitted adequate surgical exposure for cardiopulmonary bypass,
      aortic valve replacement and coronary revascularization procedures.

PMID- 9761450
TI  - Images in cardio-thoracic surgery. Giant benign localized fibrous tumor of the
      pleura.

PMID- 9761451
TI  - A case of extreme negative intrathoracic pressure.

PMID- 9761452
TI  - The glutamate transporter, GLT-1, is expressed in cultured hippocampal neurons.
AB  - There are multiple subtypes of Na+-dependent glutamate transporters. Several
      studies suggest that EAAC1 and EAAT4 are expressed in neurons, while GLT-1 and
      GLAST expression is thought to be restricted to glia. In the present study,
      expression of GLT-1 and EAAC1 was examined in cultured rat hippocampal neurons
      using single cell mRNA amplification and immunocytochemistry with subtype
      specific antibodies. GLT-1 and EAAC1 mRNAs were observed in all neurons examined.
      Neuronal phenotype was confirmed in these cells by expression of neurofilament
      (NF-L) mRNA and absence of glial fibrillary acidic protein (GFAP) mRNA. EAAC1
      immunoreactivity was observed in essentially all cells which expressed neuron
      specific enolase (NSE) and GLT-1 immunoreactivity was detected in the majority
      (approximately 90%) of NSE-positive cells. Consistent with the glial expression
      of GLT-1, GLT-1 immunoreactivity was also observed in NSE-negative cells. These
      studies provide evidence that GLT-1 expression is not intrinsically restricted to
      glial cells, but can occur in neurons under certain circumstances.

PMID- 9761453
TI  - Interferon beta-1b inhibits reactive oxygen species production in peripheral
      blood monocytes of patients with relapsing-remitting multiple sclerosis.
AB  - We studied the rate of reactive oxygen species (ROS) production by monocytes 'ex
      vivo' in a cohort of healthy individuals, in a group of MS patients undergoing
      treatment with interferon beta-1b and another group of MS patients who refused
      treatment with interferon beta-1b. The rate of ROS production in healthy
      individuals was slightly lower than in non-treated MS patients. The lower rate of
      ROS production was obtained in monocytes of MS patients treated with interferon
      beta-1b. These results indicate that the treatment of relapsing-remitting MS
      patients with interferon beta-1b rendered the NADPH oxidase of the monocytes less
      sensitive to trigger reactive oxygen species (ROS).

PMID- 9761454
TI  - A new procedure for determining ganglioside GD3 a potential glial cell activation
      marker in cerebrospinal fluid.
AB  - Increased amounts of ganglioside GD3 [II3 (NeuAc)2-LacCer], associated with
      reactive gliosis, have been documented in a variety of neurodegenerative
      disorders. GD3 expression has also been reported in microglial cells, not only
      during development but also in reactive states, where the glial activation is
      considered to be part of the repair process. It is important to find markers in
      cerebrospinal fluid that will enable us to identify damage and register changes
      in pathological processes within the brain. A sensitive and practically
      applicable method for determination of GD3 ganglioside in cerebrospinal fluid has
      been developed. The procedure, which includes extraction, purification on silica
      gel and thin-layer enzyme-linked immunostaining, also allows determination of
      sulphatide, a marker of demyelinating processes, in the same portion of CSF. The
      method has been applied to CSF samples from 101 normal individuals aged 2-83
      years. The GD3 concentration was found to be significantly correlated to age and
      reflecting the concentrations within the brain. GD3 ganglioside analysis by means
      of this method might be useful for studying glial changes during brain maturation
      as well as in brain disorders.

PMID- 9761456
TI  - A2a adenosine receptors: guanine nucleotide derivative regulation in porcine
      striatal membranes and digitonin soluble fraction.
AB  - We report the characterization of A2a adenosine receptors (A2aARs) in porcine
      striatal membranes and their solubilization (25%) by the detergent digitonin.
      After solubilization, the drug specificity and equilibrium [3H]CGS-21680 ([3H]2
      (4-(2-carboxyethyl)phenylethylamino)-5'-N-ethyl-carboxamido -adenosine) binding
      parameters were virtually identical to those obtained in intact membranes,
      indicating a conservation of the binding site after the removal of receptors from
      their lipid environment. Gel filtration on a calibrated Superdex 200 HR column
      revealed a main [3H]CGS-21680 binding peak with an apparent molecular weight of
      171,000+/-9000 Da. In membranes, Scatchard analysis of saturation data carried
      out in a wide range of radioligand concentration (1-100 nM) resulted in a
      biphasic curve and, in accordance with the two binding sites model, yielded a Kd1
      = 7.4+/-0.5 and Kd2 = 53.1+/-3.6 nM, a Bmax1 = 186+/-15 fmol/mg protein and a
      Bmax2 = 285+/-20 fmol/mg protein, respectively. In the presence of guanosine-5'-O
      (3-thiotriphosphate) (GTPgamma[S]) a shift from two affinity states to a single
      one was evidenced (Kd = 28.5+/-5.9 nM) and a Bmax value of 504+/-10 fmol/mg
      protein found. In the soluble extract, only one high-affinity state was detected
      (Kd = 19.3+/-1.1 nM and Bmax = 285+/-20 fmol/mg protein) and, in the presence of
      GTPgamma[S]), a two site model likewise provided a significantly (P < 0.01)
      better fit (Kd1 = 13.9+/-1.2 nM and Kd2 = 72.1+/-6.9 nM, Bmax1 = 125+/-10 fmol/mg
      protein and Bmax2 = 375+/-19 fmol/mg protein, respectively). These results
      suggest a close relation between the receptor and G protein solubilized as a
      functional unit and open the way to its purification.

PMID- 9761455
TI  - Intracerebroventricular administration of quinolinic acid induces a selective
      decrease of inositol(1,4,5)-trisphosphate receptor in rat brain.
AB  - [3H]inositol(1,4,5)-trisphosphate (IP3) binding studies have shown decreased
      [3H]IP3 binding to brain tissue in several neurodegenerative diseases, including
      Alzheimer's and Huntington's diseases. In addition, previous results obtained
      from brains of Alzheimer patients indicated a reduction of IP3-receptor protein
      correlated to neuronal loss. The neurotoxic effect of the glutamate receptor
      agonist quinolinic acid (QUIN) was therefore examined with respect to the level
      of IP3-receptor immunoreactivity in rat brain. Neuronal lesions were estimated
      with antibodies to marker proteins for striatal medium-sized spiny neurons
      (dopamine- and cyclic AMP-regulated phosphoprotein, Mr 32,000; DARPP-32),
      synaptic vesicles (synaptophysin), mitochondria (phosphate-activated glutaminase;
      PAG) and glial cells (glial fibrillary acidic protein; GFAP). Injection of QUIN
      into rat neostriatum induced a massive loss of striatal medium-sized spiny
      neurons, and led to a comparable loss of IP3-receptor and PAG immunoreactivity,
      suggesting a neuronal localisation of both these proteins. In an effort to induce
      less pronounced excitotoxic damage, intracerebroventricular infusion of QUIN was
      performed. Following this lesion, the neostriatum showed a negligible loss of
      DARPP-32 immunoreactivity (-11+/-5%), but contained only 43+/-3% of IP3-receptor
      immunoreactivity levels compared to controls. In the hippocampus, cerebellum and
      entorhinal cortex, the IP3-receptor loss was less pronounced. The decrease in the
      level of IP3-receptor immunoreactivity appears to be selective with respect to
      the other proteins studied, and the IP3-receptor thus shows extreme sensitivity
      to QUIN neurotoxicity in the neostriatum.

PMID- 9761457
TI  - Acetylcholinesterase at high catalytic efficiency and substrate specificity in
      the optic lobe of Eledone moschata (Cephalopoda: Octopoda): biochemical
      characterization and histochemical localization.
AB  - In the optic lobe of the cephalopod mollusc Eledone moschata, two
      acetylcholinesterase forms I and II were detected, both showing a marked active
      site specificity with differently sized substrates. Catalytic efficiency
      (kcat/Km) of the prevailing form II is similar to that of acetylcholinesterases
      from vertebrate nervous system. Enzyme forms I and II were co-purified from a
      high-salt-Triton X-100 soluble extract of optic lobe by consecutive affinity
      chromatographies on procainamide- and concanavalin A-Sepharose columns and then
      separately obtained by preparative density gradient centrifugation. According to
      gel-filtration chromatography, sedimentation analysis and SDS-PAGE, the major
      form II is an amphiphilic globular dimer (135-136 kDa, 6.3-7.4 S) of monomers (66
      kDa) S-S linked between terminal segments. Phosphatidylinositol anchors give cell
      membrane insertion, self-aggregation and detergent (Triton X-100, Brij 97)
      interaction. Form I, characterized only in part owing to its small amount, showed
      molecular size (129 kDa) and sedimentation coefficient (7.5 S) similar to those
      of form II; it is likely to be attached to the cell membrane by electrostatic
      interactions. Both forms behaved similarly with various inhibitors and underwent
      excess-substrate inhibition. The results obtained suggest a common origin of both
      form I and II from a single gene. The former could be a degradation product of
      the prevailing one (II), which is likely to be functional in cholinergic
      synapses.

PMID- 9761458
TI  - Mouse interleukin-6 stimulates the HPA axis and increases brain tryptophan and
      serotonin metabolism.
AB  - Neuroendocrine and neurochemical responses were studied following administration
      of recombinant mouse IL-6 (mIL-6) to mice. Intravenous (iv) or intraperitoneal
      (ip) injection of mIL-6 caused a rapid and short-lived activation of the
      hypothalamo-pituitary-adrenocortical (HPA) axis, as indicated by increases in
      plasma ACTH and corticosterone, with peak responses around 30-60 min. These
      responses contrast with those to ip mIL-1beta which is substantially more potent
      and induces a greater response which does not peak until about 2 h following ip
      administration. Unlike IL-1 and lipopolysaccharide (LPS), IL-6 had no detectable
      effect on norepinephrine metabolism. However, tryptophan concentrations were
      elevated in most brain regions studied 1-2 h following iv mIL-6, and 2 h
      following ip mIL-6, significantly later than the peak HPA response. 5
      hydroxyindoleacetic acid (5-HIAA) and the ratio of 5-HIAA to serotonin (5-HT)
      were elevated at around the same time in the brain stem, and occasionally in
      other brain regions. These responses were observed at doses of mIL-6 as low as
      0.25 microg, and near maximal effects were achieved by 0.5 microg. Recombinant
      human IL-6 elicited similar responses, but was significantly less potent. Heat
      treated mIL-6 elicited none of the responses. Serum amyloid A protein (SAA)
      concentrations were not elevated until 4 h after iv or ip mIL-6 administration,
      suggesting that the neuroendocrine and neurochemical changes were not secondary
      to an acute phase protein response. Intracerebroventricular injection of mIL-6
      also elevated tryptophan and 5-HIAA in the hypothalamus and brain stem.
      Pretreatment of mice with the cyclooxygenase inhibitor, indomethacin, or the
      nitric oxide synthase inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME)
      did not attenuate the mIL-6 induced neuroendocrine or neurochemical responses.
      However, the ganglionic blocking drug, chlorisondamine, prevented the increases
      in tryptophan and 5-HIAA:5-HT ratios. IL-6 may contribute to the HPA and
      indoleaminergic responses to LPS and IL-1. It is possible that the increases of
      tryptophan and serotonin metabolism may contribute to some of the biological
      effects of IL-6.

PMID- 9761459
TI  - Complex polyamine effects on [3H]MDL 105,519 binding to the NMDA receptor glycine
      site.
AB  - Several studies have suggested that polyamines modulate the interaction of
      glycine with the NMDA receptor. We have further investigated the effects of
      polyamines using the NMDA receptor glycine site antagonist [(E)-3-(2-phenyl-2
      carboxyethenyl)-4,6-dichloro-1H-indole-2-carbox ylic acid] ([3H]MDL 105,519).
      [3H]MDL 105,519 binding assays were performed using well washed membranes
      prepared from frozen rat brains. The polyamines spermine and spermidine increased
      the fraction of non-specific binding (determined by the addition of 1 mM glycine)
      in the [3H]MDL 105,519 binding assay from 40-60% when spermine or spermidine
      concentration was increased from 1 to 100 microM. Polyamine agonists spermine,
      spermidine and 1,5-(diethylamino)piperidine (30 microM) did not have a
      significant effect on displacement of [3H]MDL 105,519 binding by glycine or
      glycine site antagonists. Similarly, the polyamine antagonist arcaine did not
      have a significant effect on displacement of [3H]MDL 105,519 binding by glycine
      or glycine site antagonists. However, spermidine significantly depressed the
      potency of MDL 105,519 in displacing [3H]dizocilpine binding. These data suggest
      that [3H]MDL 105,519 may preferentially bind to a polyamine insensitive form of
      the NMDA receptor.

PMID- 9761461
TI  - Diverse effects of mild and potent goitrogens on blood-brain barrier nutrient
      transport.
AB  - Populations living in goitre endemic areas consume foods rich in a variety of
      goitrogens of different potencies and some are severely hypothyroid. Recently we
      observed in Wistar/NIN rats that chronic feeding of KSCN to dams produced only a
      moderate hypothyroidism and decreased the transport of 2-deoxy-D-glucose (2-DG)
      across the blood-brain barrier (BBB) in the offspring. The present studies were
      conducted to assess whether severe hypothyroidism would have greater effect on
      BBB nutrient transport. It has now been observed that weaning the pups of KSCN
      fed dams on to KSCN diet for four weeks had no further effect either on their
      thyroid status or the BBB 2-DG transport. However, feeding KSCN to rats through
      two generations produced somewhat severe hypothyroidism in F2 pups than that in
      F1 pups. Interestingly, unlike in F1 pups, the BBB transport of all the three
      nutrients tested (2-DG, Leu and Tyr) was significantly decreased in F2 pups,
      albeit to a small extent (10-15%). On the other hand the potent goitrogen: methyl
      mercaptoimidazole (MMI) even on short term feeding to pregnant dams produced very
      severe hypothyroidism in the offspring [Serum T4:0.55+/-0.09 microg/dl vs 4.96+/
      0.85 in controls]. Surprisingly, the BBB transport of 2-DG, Leu, Tyr and also
      sucrose, the background marker, was significantly increased in these pups (20
      30%). The diverse effects of goitrogen-induced moderate and severe hypothyroidism
      observed here on the BBB nutrient transport probably suggest different mechanisms
      for iodine deficiency disorders of different aetiologies and hence the need for
      discrete approaches for their management.

PMID- 9761460
TI  - Comparison of the effects of hydrogen peroxide, 4-hydroxy-2-nonenal and beta
      amyloid (25-35) upon calcium signalling.
AB  - The neurotoxic beta-amyloid (Abeta) peptide fragment Abeta(25-35) has been
      suggested to exert its deleterious effects on cells via production of hydrogen
      peroxide. In human platelets and in the presence of DMSO to prevent production of
      hydroxyl radicals from hydrogen peroxide, both Abeta(25-35) and hydrogen peroxide
      were found to increase intracellular calcium levels. Hydrogen peroxide in
      addition reduced the calcium response to thrombin, whereas this was not seen with
      Abeta(25-35). A similar pattern of effects to those seen with hydrogen peroxide
      were also seen with the neurotoxic aldehyde lipid peroxidation product 4-hydroxy
      2-nonenal (HNE). The initial increase in calcium produced by hydrogen peroxide
      was not affected by EGTA, but was partially prevented by dithiothreitol. The
      calcium response to Abeta(25-35) [which was also seen with Abeta(1-40) and
      Abeta(1-42) but not with the inactive peptide Abeta(40-1)] consisted of an EGTA
      sensitive and an EGTA-resistant component, of which the latter was also sensitive
      to DTT. Hydrogen peroxide increased basal phosphoinositide breakdown in rat brain
      miniprisms and decreased the responses to noradrenaline, carbachol and veratrine.
      The specific binding of [3H]inositol-1,4,5-trisphosphate ([3H]Ins(1,4,5)P3) to
      its receptor recognition site in human platelet membranes was increased by
      Abeta(25-35) but remained unchanged following hydrogen peroxide treatment. It is
      concluded that under conditions where production of hydroxyl radicals from
      hydrogen peroxide is blocked, hydrogen peroxide and Abeta(25-35) produce their
      effects on calcium by affecting the mobilisation of intracellular calcium. The
      qualitative differences in the calcium responses of these two agents can be
      explained (a) by an additional effect of Abeta(25-35) upon calcium entry and (b)
      by differences in their effects upon the Ins(1,4,5)P3 receptor.

PMID- 9761462
TI  - Expression of G-protein subtypes in cultured cerebral endothelial cells.
AB  - This paper describes Western-blotting evidence for the presence of various
      guanine nucleotide binding proteins, G-proteins in cultured rat cerebral
      endothelial cells (CECs) and two immortalized cerebral endothelial cell lines,
      RBE4 and GP8. By using specific antibodies raised against known sequences of
      appropriate G-protein types that were previously characterized, we demonstrated
      the presence of Gsalpha, Gi2alpha, Gi3alpha, Gq/11alpha, Goalpha and Gbeta in
      cell lysates of primary cultures of CECs, and plasma membranes of RBE4 and GP8
      cells. The appearance of Goalpha proteins in CECs might be of special importance,
      since they were not detected in peripheral endothelial cells in previous studies.
      Isoproterenol and bradykinin displayed significant, dose-dependent stimulation of
      [35S]GTPgammaS binding above basal values. This assay, reflecting the GDP-GTP
      exchange reaction on Galpha-subunits by receptor agonists, suggested that there
      were functional, G-protein coupled beta-adrenergic and bradykinin receptors in
      these systems. No significant stimulation of [35S]GTP7gammaS binding was noted
      with serotonin under our experimental conditions. Since stimulation of
      [35S]GTPgammaS binding by isoproterenol and bradykinin was additive, it was
      concluded that different Galpha proteins were activated by these two ligands. In
      analogy to other systems, activation of Gs is most likely by isoproterenol, while
      Gi and/or Gq/11 proteins might be activated by bradykinin receptors. The possible
      significance of the receptors and G-proteins detected is being discussed in the
      functioning of cerebral endothelium, and thus the blood-brain barrier.

PMID- 9761464
TI  - Immunohistochemical localization of taurine in the retina of developing and adult
      human and adult monkey.
AB  - The localization of taurine in the retina of fetal (12-25 weeks of gestation),
      postnatal (five-month-old infant) and adult human (35- and 65-year-old) was
      examined by immunohistochemistry. Additionally, retinas of fresh adult monkey,
      which served as positive controls, were employed. No immunoreactivity was found
      in the fetal retinas from 12-15 weeks of gestation. At 1617 weeks of gestation,
      the ganglion cells and some of their axons were conspicuously labelled for
      taurine. At 18-19 weeks, Muller glial endfeet, the inner plexiform layer, some
      amacrine and putative horizontal cells and photoreceptors showed moderate
      immunoreactivity. With further development at 20-21 and 24-25 weeks of gestation,
      the immunoreactivity was prominent in Muller cell endfeet, some bipolar cells and
      in horizontal cells that were aligned in a row in the inner nuclear layer, close
      to the fovea. At both fetal stages, the photoreceptors and horizontal cells
      showed strong immunoreactivity. In the postnatal infant retina, taurine
      immunoreactivity was present in some amacrine cells and photoreceptor inner
      segments and nuclei, but not in ganglion and horizontal cells, which was also the
      pattern noted in the adult monkey and human retinas. With development, a shift in
      the intensity of taurine immunoreactivity was noted towards the outer retina. The
      expression of taurine immunoreactivity in most fetal retinal neurons implies a
      role for this amino acid in the normal development as well as maturation of human
      retina.

PMID- 9761463
TI  - Alterations of striatal cholinergic receptors after lesioning of the substantia
      nigra.
AB  - Dopamine deficiency syndrome is known to cause cholinergic hyperactivity.
      Therefore, it was hypothesized that the said phenomenon may be due to enhanced
      cholinergic receptor functions. In the present study we examined the changes in
      striatal dopaminergic and cholinergic receptors in unilateral substantia nigra
      lesioned rats that showed vigorous ipsilateral rotation (total turns > 300) in
      response to apomorphine (1 mg kg(-1) ip). [3H] Spiperone ([3H]-SP) and [3H]
      quinuclidinyl benzilate ([3H]-QNB) bindings were performed in the striata of the
      lesioned animals. There was no significant difference in the dissociation
      equilibrium constant values (Kd) between the lesioned and non-lesioned sides.
      However, a significant difference in the maximum receptor density (Bmax) of both
      [3H]-SP and [3H]-QNB bindings was observed between the lesioned and non-lesioned
      sides. The Bmax of [3H]-SP binding was significantly decreased on the lesioned
      side, whereas the Bmax of the [3H]-QNB binding was significantly increased. These
      results support the hypothesis that deficiencies of the dopaminergic system cause
      overactivity of the cholinergic system in the striatum.

PMID- 9761465
TI  - Increases in levels of brain-derived neurotrophic factor mRNA and its promoters
      after transient forebrain ischemia in the rat brain.
AB  - Expression of brain-derived neurotrophic factor (BDNF) may play a role in the
      mechanism of neuronal cell death after cerebral ischemia. We investigated the
      changes in levels of mRNAs encoding BDNF and its promoters in the rat brain after
      transient forebrain ischemia. Transient forebrain ischemia was induced by
      occlusion of bilateral common carotid arteries and systemic hypotension for 8
      min. The alterations in BDNF gene expression in the hippocampus and in the
      cerebral cortex were examined by in situ hybridization using a mouse BDNF cDNA
      probe and cDNA probes including exon-specific promoters. BDNF transcripts were
      rapidly enhanced after the ischemic insult, both in the hippocampus and the
      cerebral cortex. NBQX suppressed the enhanced gene expression of BDNF markedly in
      the dentate gyrus (DG). In contrast, MK-801 had little effect on BDNF expression.
      In the piriform cortex, MK-801 or NBQX reduced the expression only moderately.
      After the ischemic insult, promoter specific BDNF 5'-exon I and exon III were
      increased remarkably in the DG. The increase in exon I in DG was suppressed
      partially by MK-801 and NBQX, while the increase in exon III in CA3 was
      suppressed by MK-801 but that in DG was not suppressed by either antagonist. In
      the piriform cortex, exon III was increased remarkably and this increase was not
      influenced by either agonist. These results suggest that the gene expression of
      BDNF was enhanced by transient ischemia both in the hippocampus and the cerebral
      cortex and that the cerebral ischemia stimulated at least two different promoter-
      and neuron type-specific pathways regulating expression of the BDNF gene mediated
      by glutamate receptors of non-NMDA type and NMDA type.

PMID- 9761466
TI  - Class-directed structure determination: foundation for a protein structure
      initiative.
AB  - The recent sequencing of many complete genomes, combined with the development of
      methods that allow rapid structure determination for many proteins, has changed
      the way in which protein structure determinations can be approached. One-by-one
      determinations of individual protein structures will soon be augmented by class
      directed structure analyses in which a group of proteins is targeted and
      structures of representative members are determined and used to represent the
      entire group. Such a shift in approach would be the foundation for a broad
      protein structure initiative targeting classes of proteins important for
      biotechnology and for a fundamental understanding of protein function.

PMID- 9761467
TI  - Kinetic epitope mapping of the chicken lysozyme.HyHEL-10 Fab complex: delineation
      of docking trajectories.
AB  - The rate constants, k(on), for the formation of hen (chicken) lysozyme (HEWL).
      Fab-10 complexes have been determined for wild-type (WT) and epitope-mutated
      lysozymes by a homogeneous solution method based on the 95% reduced enzymatic
      activity of the complex. The values fall within a narrow 10-fold range [(0.18 to
      1.92) x 10(6) M(-1)s(-l)]. The affinity constants, K(D), cover a broader, 440
      fold, range from 0.075 to 33 nM. Values of K(D) as high as 7 microM were obtained
      for the complexes prepared from some mutations at HEWL positions 96 and 97, but
      the associated kinetic constants could not be determined. The values of k(on) are
      negatively correlated with side-chain volume at position 101HEWL, but are
      essentially independent of this parameter for position 21HEWL substitutions. The
      multiple mutations made at positions 21HEWL and 101HEWL provide sufficient
      experimental data on complex formation to evaluate phi values [phi =
      (deltadeltaGon)/(deltadeltaG(D))] at these two positions to begin to define
      trajectories for protein-protein association. The data, when interpreted within
      the concept of a two-step association sequence embracing a metastable encounter
      complex intermediate, argue that the rate determining step at position 21HEWL
      (phiavg = 0.2) is encounter complex formation, but the larger phi(avg) value of
      0.36 experienced for most position 101HEWL mutations indicates a larger
      contribution from the post-encounter annealing process at this site for these
      replacements.

PMID- 9761468
TI  - Quantitative evaluation of the chicken lysozyme epitope in the HyHEL-10 Fab
      complex: free energies and kinetics.
AB  - The hen (chicken) egg-white lysozyme (HEWL) epitope for the monoclonal antibody
      HyHEL-10 Fab (Fab-10) was investigated by alanine scan mutagenesis. The
      association rate constants (k(on)) for the HEWL Fab-10 complexes were obtained
      from the homogenous solution method described in the preceding paper (Taylor et
      al., 1998). A new method for determining the dissociation rate constant (k(off))
      for the complex, by trapping nascent free antibody with an inactive HEWL mutant
      is described. The values of k(on) fall within a factor of 2 of the wild-type (WT)
      HEWL value (1.43+/-0.13 X 10(6)M(-1)s(-1)), while the increases in k(off)more
      nearly reflect the total change in free energies of the complex (deltadeltaG(D)).
      The dissociation constants (K(D)) were measured directly in those cases where
      satisfactory kinetic data could not be obtained. The Y20A, K96A, and K97A
      HEWL.Fab-10 complexes are destabilized by more than 4 kcal/mol compared to the WT
      complex. The R21A, L75A, and D101A antibody complexes are moderately destabilized
      (0.7 < deltadeltaG(D)< or = 1.0 kcal/mol). Additional mutations of the "hotspot"
      residues (Tyr20, Lys96, Lys97) were constructed to probe, more precisely, the
      nature of their contributions to complex formation. The results show that the
      entire hydrocarbon side chains of Tyr20 and Lys97, and only the epsilon-amino
      group of Lys96, contribute to the stability of the complex. The value of
      deltadeltaG(D) for the R21A mutant complex is a distinct outlier in the Arg21
      replacement series demonstrating the importance of supplementing alanine scan
      mutagenesis with additional mutations.

PMID- 9761469
TI  - Conversion of a beta-strand to an alpha-helix induced by a single-site mutation
      observed in the crystal structure of Fis mutant Pro26Ala.
AB  - The conversion from an alpha-helix to a beta-strand has received extensive
      attention since this structural change may induce many amyloidogenic proteins to
      self-assemble into fibrils and cause fatal diseases. Here we report the
      conversion of a peptide segment from a beta-strand to an alpha-helix by a single
      site mutation as observed in the crystal structure of Fis mutant Pro26Ala
      determined at 2.0 A resolution. Pro26 in Fis occurs at the point where a flexible
      extended beta-hairpin arm leaves the core structure. Thus it can be classified as
      a "hinge proline" located at the C-terminal end of the beta2-strand and the N
      terminal cap of the A alpha-helix. The replacement of Pro26 to alanine extends
      the A alpha-helix for two additional turns in one of the dimeric subunits;
      therefore, the structure of the peptide from residues 22 to 26 is converted from
      a beta-strand to an alpha-helix. This result confirms the structural importance
      of the proline residue located at the hinge region and may explain the mutant's
      reduced ability to activate Hin-catalyzed DNA inversion. The peptide (residues 20
      to 26) in the second monomer subunit presumably retains its beta-strand
      conformation in the crystal; therefore, this peptide shows a "chameleon-like"
      character since it can adopt either an alpha-helix or a beta-strand structure in
      different environments. The structure of Pro26Ala provides an additional example
      where not only the protein sequence, but also non-local interactions determine
      the secondary structure of proteins.

PMID- 9761470
TI  - Anatomy of protein pockets and cavities: measurement of binding site geometry and
      implications for ligand design.
AB  - Identification and size characterization of surface pockets and occluded cavities
      are initial steps in protein structure-based ligand design. A new program, CAST,
      for automatically locating and measuring protein pockets and cavities, is based
      on precise computational geometry methods, including alpha shape and discrete
      flow theory. CAST identifies and measures pockets and pocket mouth openings, as
      well as cavities. The program specifies the atoms lining pockets, pocket
      openings, and buried cavities; the volume and area of pockets and cavities; and
      the area and circumference of mouth openings. CAST analysis of over 100 proteins
      has been carried out; proteins examined include a set of 51 monomeric enzyme
      ligand structures, several elastase-inhibitor complexes, the FK506 binding
      protein, 30 HIV-1 protease-inhibitor complexes, and a number of small and large
      protein inhibitors. Medium-sized globular proteins typically have 10-20
      pockets/cavities. Most often, binding sites are pockets with 1-2 mouth openings;
      much less frequently they are cavities. Ligand binding pockets vary widely in
      size, most within the range 10(2)-10(3)A3. Statistical analysis reveals that the
      number of pockets and cavities is correlated with protein size, but there is no
      correlation between the size of the protein and the size of binding sites. Most
      frequently, the largest pocket/cavity is the active site, but there are a number
      of instructive exceptions. Ligand volume and binding site volume are somewhat
      correlated when binding site volume is < or =700 A3, but the ligand seldom
      occupies the entire site. Auxiliary pockets near the active site have been
      suggested as additional binding surface for designed ligands (Mattos C et al.,
      1994, Nat Struct Biol 1:55-58). Analysis of elastase-inhibitor complexes suggests
      that CAST can identify ancillary pockets suitable for recruitment in ligand
      design strategies. Analysis of the FK506 binding protein, and of compounds
      developed in SAR by NMR (Shuker SB et al., 1996, Science 274:1531-1534),
      indicates that CAST pocket computation may provide a priori identification of
      target proteins for linked-fragment design. CAST analysis of 30 HIV-1 protease
      inhibitor complexes shows that the flexible active site pocket can vary over a
      range of 853-1,566 A3, and that there are two pockets near or adjoining the
      active site that may be recruited for ligand design.

PMID- 9761471
TI  - Effects of salt bridges on protein structure and design.
AB  - Theoretical calculations (Hendsch ZS & Tidor B, 1994, Protein Sci 3:211-226) and
      experiments (Waldburger CD et al., 1995, Nat Struct Biol 2:122-128; Wimley WC et
      al., 1996, Proc Natl Acad Sci USA 93:2985-2990) suggest that hydrophobic
      interactions are more stabilizing than salt bridges in protein folding. The lack
      of apparent stability benefit for many salt bridges requires an alternative
      explanation for their occurrence within proteins. To examine the effect of salt
      bridges on protein structure and stability in more detail, we have developed an
      energy function for simple cubic lattice polymers based on continuum
      electrostatic calculations of a representative selection of salt bridges found in
      known protein crystal structures. There are only three types of residues in the
      model, with charges of -1, 0, or + 1. We have exhaustively enumerated
      conformational space and significant regions of sequence space for three
      dimensional cubic lattice polymers of length 16. The results demonstrate that,
      while the more highly charged sequences are less stable, the loss of stability is
      accompanied by a substantial reduction in the degeneracy of the lowest-energy
      state. Moreover, the reduction in degeneracy is greater due to charges that pair
      than for lone charges that remain relatively exposed to solvent. We have also
      explored and illustrated the use of ion-pairing strategies for rational
      structural design using model lattice studies.

PMID- 9761472
TI  - Uclacyanins, stellacyanins, and plantacyanins are distinct subfamilies of
      phytocyanins: plant-specific mononuclear blue copper proteins.
AB  - The cDNAs encoding plantacyanin from spinach were isolated and characterized. In
      addition, four new cDNA sequences from Arabidopsis ESTs were identified that
      encode polypeptides resembling phytocyanins, plant-specific proteins constituting
      a distinct family of mononuclear blue copper proteins. One of them encodes
      plantacyanin from Arabidopsis, while three others, designated as uclacyanin 1, 2,
      and 3, encode protein precursors that are closely related to precursors of
      stellacyanins and a blue copper protein from pea pods. Comparative analyses with
      known phytocyanins allow further classification of these proteins into three
      distinct subfamilies designated as uclacyanins, stellacyanins, and plantacyanins.
      This specification is based on (1) their spectroscopic properties, (2) their
      glycosylation state, (3) the domain organization of their precursors, and (4)
      their copper-binding amino acids. The recombinant copper binding domain of
      Arabidopsis uclacyanin 1 was expressed, purified, and shown to bind a copper atom
      in a fashion known as "blue" or type 1. The mutant of cucumber stellacyanin in
      which the glutamine axial ligand was substituted by a methionine (Q99M) was
      purified and shown to possess spectroscopic properties similar to uclacyanin 1
      rather than to plantacyanins. Its redox potential was determined by cyclic
      voltammetry to be +420 mV, a value that is significantly higher than that
      determined for the wild-type protein (+260 mV). The available structural data
      suggest that stellacyanins (and possibly other phytocyanins) might not be
      diffusible electron-transfer proteins participating in long-range electron
      transfer processes. Conceivably, they are involved in redox reactions occurring
      during primary defense responses in plants and/or in lignin formation.

PMID- 9761473
TI  - Electrostatic interactions in the acid denaturation of alpha-lactalbumin
      determined by NMR.
AB  - alpha-Lactalbumin (alpha-LA) undergoes a pH-dependent unfolding from the native
      state to a partially unfolded state (the molten globule state). To understand the
      role of electrostatic interactions in protein denaturation, NMR and CD pH
      titration experiments are performed on guinea pig alpha-LA. Variation of pH over
      the range of 7.0 to 2.0 simultaneously leads to the acid denaturation of the
      protein and the titration of individual ionizable groups. The pH titrations are
      interpreted in the context of these coupled events, and indicate that acid
      denaturation in alpha-LA is a cooperative event that is triggered by the
      protonation of two ionizable residues. Our NMR results suggest that the critical
      electrostatic interactions that contribute to the denaturation of alpha-LA are
      concentrated in the calcium binding region of the protein.

PMID- 9761474
TI  - The de novo design of a rubredoxin-like Fe site.
AB  - A redox center similar to that of rubredoxin was designed into the 56 amino acid
      immunoglobulin binding B1 domain of Streptococcals protein G. The redox center in
      rubredoxin contains an iron ion tetrahedrally coordinated by four cysteine
      residues, [Fe(S-Cys)4](-1),(-2). The design criteria for the target site included
      taking backbone movements into account, tetrahedral metal-binding, and
      maintaining the structure and stability of the wild-type protein. The optical
      absorption spectrum of the Co(II) complex of the metal-binding variant is
      characteristic of tetrahedral chelation by four cysteine residues. Circular
      dichroism and nuclear magnetic resonance measurements reveal that the metal-free
      and Cd(II)-bound forms of the variant are folded correctly and are stable. The
      Fe(III) complex of the metal-binding mutant reproduces the optical and the
      electron paramagnetic resonance spectra of oxidized rubredoxin. This demonstrates
      that the engineered protein chelates Fe(III) in a tetrahedral array, and the
      resulting center is similar to that of oxidized rubredoxin.

PMID- 9761475
TI  - Structural/functional properties of the Glu1-HSer57 N-terminal fragment of human
      plasminogen: conformational characterization and interaction with kringle
      domains.
AB  - The Glu1-Val79 N-terminal peptide (NTP) domain of human plasminogen (Pgn) is
      followed by a tandem array of five kringle (K) structures of approximately 9 kDa
      each. K1, K2, K4, and K5 contain each a lysine-binding site (LBS). Pgn was
      cleaved with CNBr and the Glul-HSer57 N-terminal fragment (CB-NTP) isolated. In
      addition, the Ile27-Ile56 peptide (L-NTP) that spans the doubly S-S bridged loop
      segment of NTP was synthesized. Pgn kringles were generated either by proteolytic
      fragmentation of Pgn (K4, K5) or via recombinant gene expression (rK1, rK2, and
      rK3). Interactions of CB-NTP with each of the Pgn kringles were monitored by 1H
      NMR at 500 MHz and values for the equilibrium association constants (Ka)
      determined: rK1, Ka approximately 4.6 mM(-1); rK2, Ka approximately 3.3 mM(-1);
      K4, Ka approximately 6.2 mM-'; K5, K, 2.3 mM(-1). Thus, the lysine-binding
      kringles interact with CB-NTP more strongly than with Nalpha-acetyl-L-lysine
      methyl ester (Ka < 0.6 mM(-l), which reveals specificity for the NTP. In
      contrast, CB-NTP does not measurably interact with rK3. which is devoid of a LBS.
      CB-NTP and L-NTP 1H-NMR spectra were assigned and interproton distances estimated
      from 1H-1H Overhauser (NOESY) experiments. Structures of L-NTP and the Glul-Ile27
      segment of CB-NTP were computed via restrained dynamic simulated annealing/energy
      minimization (SA/EM) protocols. Conformational models of CB-NTP were generated by
      joining the two (sub)structures followed by a round of constrained SA/EM. Helical
      turns are indicated for segments 6-9, 12-16, 28-30, and 45-48. Within the Cys34
      Cys42 loop of L-NTP, the structure of the Glu-Glu-Asp-Glu-Glu39 segment appears
      to be relatively less defined, as is the case for the stretch containing Lys5O
      within the Cys42-Cys54 segment, consistent with the latter possibly interacting
      with kringle domains in intact Glul-Pgn. Overall, the CB-NTP and L-NTP fragments
      are of low regular secondary structure content-as indicated by UV-CD spectra- and
      exhibit fast amide 1H-2H exchange in 2H2O, suggestive of high flexibility.

PMID- 9761476
TI  - Lysine-50 is a likely site for anchoring the plasminogen N-terminal peptide to
      lysine-binding kringles.
AB  - Interactions between the kringle 4 (K4) domain of human plasminogen (Pgn) and
      segments of the N-terminal Glu1-Lys77 peptide (NTP) have been investigated via 1H
      NMR at 500 MHz. NTP peptide stretches devoid of Lys residues but carrying an
      internal Arg residue show negligible affinity toward K4 (equilibrium association
      constant Ka < 0.05 mM(-1)). In contrast, while most fragments containing an
      internal Lys residue exhibit affinities comparable to that shown by the blocked
      Lys derivative Nalpha-acetyl-L-lysine-methyl ester (Ka approximately 0.2 mM(-1),
      peptides encompassing Lys50O consistently show higher Ka values. Among the
      investigated linear peptides, Nalpha-acetyl-Ala-Phe-Tyr-His-Ser-Ser-Lys5O-Glu-Gln
      NH2 (AcAFYHSK5OEQ-NH2) exhibits the strongest interaction with K4 (Ka
      approximately 1.4 mM(-1)), followed by AcYHSK50EQ-NH2 (Ka approximately 0.9 mM(
      1)). Relative to the wild-type sequence, mutated hexapeptides exhibit lesser
      affinity for K4. When a Lys50 --> Ser mutation was introduced (==> AcYHSS50EQ
      NH2), binding was abolished. The Ile27-lle56 construct (L-NTP) contains the Lys50
      site within a loop constrained by two cystine bridges. The propensity of
      recombinant Pgn K1 (rK1) and K2 (rK2) modules, and of Pgn fragments encompassing
      the intact K4 and K5 domains, for binding L-NTP, was investigated. We find that L
      NTP interacts with rK1, rK2, K4, and K5-all lysine-binding kringles-in a fashion
      that closely mimics what has been observed for the Glul-HSer57 N-terminal
      fragment of Pgn (CB-NTP). Thus, both the constellation of kringle lysine binding
      site (LBS) aromatic residues that are perturbed upon complexation of L-NTP and
      magnitudes of kringle-L-NTP binding affinities (rK1, Ka approximately 4.3 mM(-1);
      rK2, Ka approximately 3.7 mM(-1; K4, Ka approximately 6.4 mM(1); and K5, Ka
      approximately 2.1 mM(-1)) are essentially the same as for the corresponding
      kringle-CB-NTP pairs. Molecular modeling studies suggest that the Glu39-Lys50
      stretch in NTP generates an area that complements, both topologically and
      electrostatically, the solvent-exposed kringle LBS surface.

PMID- 9761477
TI  - Human nucleotide excision repair protein XPA: extended X-ray absorption fine
      structure evidence for a metal-binding domain.
AB  - The ubiquitous, multi-enzyme, nucleotide excision repair (NER) pathway is
      responsible for correcting a wide range of chemically and structurally distinct
      DNA lesions in the eukaryotic genome. Human XPA, a 31 kDa, zinc-associated
      protein, is thought to play a major NER role in the recognition of damaged DNA
      and the recruitment of other proteins, including RPA, ERCC1, and TFIIH, to repair
      the damage. Sequence analyses and genetic evidence suggest that zinc is
      associated with a C4-type motif, C105-X2-C108-X17-C126-X2-C129, located in the
      minimal DNA binding region of XPA (M98-F219). The zinc-associated motif is
      essential for damaged DNA recognition. Extended X-ray absorption fine structure
      (EXAFS) spectra collected on the zinc associated minimal DNA-binding domain of
      XPA (ZnXPA-MBD) show directly, for the first time, that the zinc is coordinated
      to the sulfur atoms of four cysteine residues with an average Zn-S bond length of
      2.34+/-0.01 A. XPA-MBD was also expressed in minimal medium supplemented with
      cobalt nitrate to yield a blue-colored protein that was primarily (>95%) cobalt
      associated (CoXPA-MBD). EXAFS spectra collected on CoXPA-MBD show that the cobalt
      is also coordinated to the sulfur atoms of four cysteine residues with an average
      Co-S bond length of 2.33+/-0.02 A.

PMID- 9761478
TI  - The structure of serine hydroxymethyltransferase as modeled by homology and
      validated by site-directed mutagenesis.
AB  - We describe a model for the three-dimensional structure of E. coli serine
      hydroxymethyltransferase based on its sequence homology with other PLP enzymes of
      the alpha-family and whose tertiary structures are known. The model suggests that
      certain amino acid residues at the putative active site of the enzyme can adopt
      specific roles in the catalytic mechanism. These proposals were supported by
      analysis of the properties of a number of site-directed mutants. New active site
      features are also proposed for further experimental testing.

PMID- 9761479
TI  - A test of the relationship between sequence and structure in proteins: excision
      of the heme binding site in apocytochrome b5.
AB  - The water-soluble domain of rat hepatic holocytochrome b5 is an alphabeta protein
      containing elements of secondary structure in the sequence beta1-alpha1-beta4
      beta3-alpha2-alpha3-beta5- alpha4-alpha5-beta2-alpha6. The heme group is enclosed
      by four helices, a2, a3, a4, and a5. To test the hypothesis that a small b
      hemoprotein can be constructed in two parts, one forming the heme site, the other
      an organizing scaffold, a protein fragment corresponding to beta1-alpha1-beta4
      beta3-lambda-beta2-alpha6 was prepared, where lambda is a seven-residue linker
      bypassing the heme binding site. The fragment ("abridged b5") was found to
      contain alpha and beta secondary structure by circular dichroism spectroscopy and
      tertiary structure by Trp fluorescence emission spectroscopy. NMR data revealed a
      species with spectral properties similar to those of the full-length apoprotein.
      This folded form is in slow equilibrium on the chemical shift time scale with
      other less folded species. Thermal denaturation, as monitored by circular
      dichroism, absorption, and fluorescence spectroscopy, as well as size-exclusion
      chromatography-fast protein liquid chromatography (SEC-FPLC), confirmed the
      coexistence of at least two distinct conformational ensembles. It was concluded
      that the protein fragment is capable of adopting a specific fold likely related
      to that of cytochrome b5, but does not achieve high thermodynamic stability and
      cooperativity. Abridged b5 demonstrates that the spliced sequence contains the
      information necessary to fold the protein. It suggests that the dominating
      influence to restrict the conformational space searched by the chain is
      structural propensities at a local level rather than internal packing. The
      sequence also holds the properties necessary to generate a barrier to unfolding.

PMID- 9761480
TI  - Amide proton exchange measurements as a probe of the stability and dynamics of
      the N-terminal domain of the ribosomal protein L9: comparison with the intact
      protein.
AB  - Amide H/D exchange rates have been measured for the N-terminal domain of the
      ribosomal protein L9, residues 1-56. The rates were measured at pD 3.91, 5.03,
      and 5.37. At pD 5.37, 18 amides exchange slowly enough to give reliable rate
      measurements. At pD 3.91, seven additional residues could be followed. The
      exchange is shown to occur by the EX2 mechanism for all conditions studied. The
      rates for the N-terminal domain are very similar to those previously measured for
      the corresponding region in the full-length protein (Lillemoen J et al., 1997, J
      Mol Biol 268:482-493). In particular, the rates for the residues that we have
      shown to exchange via global unfolding in the N-terminal domain agree within the
      experimental error with the rates measured by Hoffman and coworkers, suggesting
      that the structure of the domain is preserved in isolation and that the stability
      of the isolated domain is comparable to the stability of this domain in intact
      L9.

PMID- 9761481
TI  - Distance geometry generates native-like folds for small helical proteins using
      the consensus distances of predicted protein structures.
AB  - For successful ab initio protein structure prediction, a method is needed to
      identify native-like structures from a set containing both native and non-native
      protein-like conformations. In this regard, the use of distance geometry has
      shown promise when accurate inter-residue distances are available. We describe a
      method by which distance geometry restraints are culled from sets of 500 protein
      like conformations for four small helical proteins generated by the method of
      Simons et al. (1997). A consensus-based approach was applied in which every inter
      Calpha distance was measured, and the most frequently occurring distances were
      used as input restraints for distance geometry. For each protein, a structure
      with lower coordinate root-mean-square (RMS) error than the mean of the original
      set was constructed; in three cases the topology of the fold resembled that of
      the native protein. When the fold sets were filtered for the best scoring
      conformations with respect to an all-atom knowledge-based scoring function, the
      remaining subset of 50 structures yielded restraints of higher accuracy. A second
      round of distance geometry using these restraints resulted in an average
      coordinate RMS error of 4.38 A.

PMID- 9761482
TI  - Compactness of the kinetic molten globule of bovine alpha-lactalbumin: a dynamic
      light scattering study.
AB  - During folding of globular proteins, the molten globule state was observed as an
      equilibrium intermediate under mildly denaturing conditions as well as a
      transient intermediate in kinetic refolding experiments. While the high
      compactness of the equilibrium intermediate of alpha-lactalbumin has been
      verified, direct measurements of the compactness of the kinetic intermediate have
      not been reported until now. Our dynamic light scattering measurements provide a
      complete set of the hydrodynamic dimensions of bovine alpha-lactalbumin in
      different conformational states, particularly in the kinetic molten globule
      state. The Stokes radii for the native, kinetic molten globule, equilibrium
      molten globule, and unfolded states are 1.91, 1.99, 2.08, and 2.46 nm,
      respectively. Therefore, the kinetic intermediate appears to be even more compact
      than its equilibrium counterpart. Remarkable differences in the concentration
      dependence of the Stokes radius exist revealing strong attractive but repulsive
      intermolecular interactions in the kinetic and equilibrium molten globule states,
      respectively. This underlines the importance of extrapolation to zero protein
      concentration in measurements of the molecular compactness.

PMID- 9761483
TI  - Electrostatic coupling to pH-titrating sites as a source of cooperativity in
      protein-ligand binding.
AB  - This paper describes an alternative mechanism for the cooperative binding of
      charged ligands to proteins. The ligand-binding sites are electrostatically
      coupled to protein side chains that can undergo protonation and deprotonation.
      The binding of one ligand alters the protein's protonation equilibrium in a
      manner that makes the the binding of the second ligand more favorable. This
      mechanism requires no conformational change to produce a cooperative effect,
      although it is not exclusive of conformational change. We present a theoretical
      description of the mechanism, and calculations on three kinds of systems: A model
      system containing one protonation site and two ligand-binding sites; a model
      system containing two protonation sites and two ligand-binding sites; and
      calbindin D9k, which contains two Ca2+-binding sites and 30 protonation sites.
      For the one-protonation-site model, it is shown that the influence of the
      protonation site can only be cooperative. The competition of this effect with the
      anticooperative effect of ligand-ligand repulsion is studied in detail. For the
      two-protonation site model, the effect can be either cooperative or, in special
      cases, anticooperative. For calbindin D9k, the calculations predict that six
      protonation sites in or near the ligand-binding sites make a cooperative
      contribution that approximately cancels the anticooperative effect of Ca2+-Ca2+
      repulsion, accounting for more than half of the total cooperative effect that is
      needed to overcome repulsion and produce the net cooperativity observed
      experimentally. We argue that cooperative mechanisms of the kind described here
      are likely when there is more than one ligand-binding site in a protein domain.

PMID- 9761484
TI  - Architecture of beta-barrel membrane proteins: analysis of trimeric porins.
AB  - We have analyzed the known three-dimensional structures of trimeric porins from
      bacterial outer membranes. The distribution of surface-exposed residues in a
      direction perpendicular to the membrane is similar to that in helical membrane
      proteins, with aliphatic residues concentrated in the central 20 A of the
      bilayer. Outside these residues is a layer of aromatic residues, followed by
      polar and charged residues. Residues in the trimer interface are more conserved
      than residues not in the interface. By comparing the interface and noninterface
      residues, an interface preference scale has been derived that may be used as a
      basis for predicting interface surfaces in monomer models.

PMID- 9761485
TI  - Characterization of recombinant human cathepsin B expressed at high levels in
      baculovirus.
AB  - The lysosomal cysteine protease cathepsin B has been studied intensely for many
      years because of its unique characteristics and its potential involvement in
      disease states. A reproducible, high yield expression system for active
      recombinant protein is key to biochemical and biophysical studies as well as
      rational drug design. Although several microbial and mammalian expression systems
      for recombinant human cathepsin B have been described, these have been limited by
      low or variable yields. Further, in some of these systems hyper-glycosylation of
      the enzyme near the active site affects its activity. We describe a baculovirus
      expression system and purification scheme that solve all of these problems.
      Yields of active, protected enzyme were reproducibly in excess of 25 mg/L. Since
      this protein was not hyper-glycosylated, it had greater activity than cathepsin B
      produced in yeast systems as indicated by a threefold increase in Kcat. In
      addition, the biophysical properties of the baculovirus-expressed cathepsin B, as
      measured by dynamic light scattering, were more amenable to crystallographic
      study since the data indicated proteins of more uniform size. Therefore, this
      system for the production of recombinant human cathepsin B constitutes a major
      improvement in both quantity and quality over those previously reported. Further,
      we demonstrate that the manner of expression and purification of this enzyme has
      profound effects on its kinetic and physical parameters.

PMID- 9761486
TI  - Pride and prejudice: the discovery of the primer for glycogen synthesis.

PMID- 9761487
TI  - Lectins: from obscurity into the limelight.

PMID- 9761488
TI  - Menin and MEN 1 gene: a model of tumour suppressor system.

PMID- 9761489
TI  - Hypertension in patients with cerebrovascular accident. To treat or not to treat?

PMID- 9761490
TI  - The renal risks of high-dose intravenous immunoglobulin treatment.

PMID- 9761491
TI  - Polymorphonuclear neutrophils in acute renal failure: new insights.

PMID- 9761492
TI  - Angiodysplasia in the renal patient: how to diagnose and how to treat?

PMID- 9761493
TI  - Recirculation, a seemingly simple concept.

PMID- 9761495
TI  - Renal function and renal disease in males or females--vive la petite difference.

PMID- 9761494
TI  - What place diuretics in long-term CAPD?

PMID- 9761496
TI  - Kt/V or solute removal index: problems in measuring and interpreting the results.

PMID- 9761497
TI  - The clotted central vein catheter for haemodialysis.

PMID- 9761498
TI  - How is the annual congress of your society managed? (Reflection on the ethics and
      finances of medical congresses).

PMID- 9761499
TI  - The impact of early normalization of haematocrit by erythropoietin on renal
      damage in the remnant kidney model.
AB  - BACKGROUND: Correction of anaemia in moderate to advanced renal failure is still
      a matter of debate because of postulated detrimental effects of erythropoietin on
      the progression of renal damage. METHODS: The renal effects of early
      normalization of haematocrit (Htc) by erythropoietin (rHuEpo) were investigated
      from the time of 5/6 nephrectomy up to 8 weeks post-intervention in three groups
      of remnant kidney model rats: untreated controls (CON), rats receiving 100 UI/kg
      body-wt of rHuEpo i.p. twice a week (EPO), and rats receiving rHuEpo in which
      periodic phlebotomies maintained Htc similar to the value of the control group
      (PHL). The latter group was included to evaluate the direct effects of rHuEpo on
      renal damage, i.e. independent from Htc correction. RESULTS: Two weeks after
      renal ablation (basal), Htc decreased in CON and PHL rats (from 49.3+/-1.4% to
      43.2+/- 1.1, P < 0.05 and from 49.6+/-1.1 to 43.3+/-1.5%, P<0.05 respectively),
      while it remained consistently normal in EPO rats (48.9+/-1.2% to 48.9+/-1.50/%,
      P<0.05 vs other groups). Thereafter Htc did not change throughout the remaining
      period in all groups. At the end of the study, with respect to basal, resting
      blood pressure increased significantly by the same extent in CON (+ 13+/-2%) and
      EPO rats (+ 15+/-5%), while it remained constant in PHL rats. Notably, creatinine
      clearance significantly decreased in CON (-53+/-8% 8 vs basal) and EPO (-38+/-8%
      vs basal), while it did not change in PHL rats. Likewise the degree of
      proteinuria as well as renal morphologic alterations and glomerular
      hypertrophy/sclerosis was similar in CON and EPO rats, and was significantly more
      severe than in the phlebotomized group. The only difference detected between CON
      and EPO group was the greater mesangial hypercellularity in rHuEpo-treated rats.
      CONCLUSION: In uraemic rats, chronic treatment with rHuEpo aimed at normalization
      of Htc beginning the early stage of renal failure does not inevitably account for
      a rise in systemic blood pressure. In addition, neither erythropoietin per se nor
      the correction of haematocrit accelerates the progression of renal damage when
      blood pressure remains constant.

PMID- 9761500
TI  - Cellular apoptosis and proliferation in experimental renal fibrosis.
AB  - BACKGROUND: The progression of chronic renal failure (CRF) is associated with the
      progressive deletion of renal cells along with the fibrosis of the kidney. We
      have studied the role of programmed cell death (apoptosis) in the progression of
      experimental CRF and renal scarring. METHODS: The sub-total (5/6th) nephrectomy
      (SNx) model of CRF was studied in adult male Wistar rats, with renal tissue
      collected from experimental and control animals on days 7, 15, 30, 60, 90, and
      120 post SNx (n = 6 per group). These were examined for morphological signs of
      apoptosis by light and electron microscopy. Further, we stained the nuclear
      chromatin by the acridine orange fluorescent method and detected signs of DNA
      cleavage by endonucleases via the principal of TUNEL staining (ApopTag). Rates of
      cellular proliferation were measured simultaneously by immunohistochemical
      staining for the proliferating cell nuclear antigen (PCNA). In addition, cell
      division was monitored by counting of morphologically mitotic motifs detectable
      by light microscopy. RESULTS: Progressive renal insufficiency associated with
      glomerulosclerosis and tubulointerstitial fibrosis took place in the majority of
      SNx rats. In these animals, we noted a marked and progressive increase in the
      number of apoptotic glomerular, tubular as well as interstitial cells. The most
      significant apoptotic changes were seen in the tubules of remnant kidneys peaking
      at day 120 post-SNx. At this stage, the increase in apoptosis compared to
      controls was 10.33+/-2.67 (M+/-SEM) fold for glomerular cells (P< or =0.006),
      26.20+/-4.56 fold for tubular cells (P < 0.0001) and 4.66+/-0.81 fold for
      interstitial cells (P< or =0.001). Parallel changes in the number of PCNA
      positive renal cells were observed. Maximal PCNA staining was seen at day 120
      when the increase with respect to controls was 14.00+/-4.93 fold (P< or = 0.05)
      for glomerular cells, 60.01+/-12.20 fold (P< or =0.05) for tubular cells and
      28.59+/-4.45 fold (P< or = 0.05) for interstitial cells. As expected, the number
      of cells undergoing division and detectable by conventional light microscopy was
      lower at any time point to those expressing PCNA. We also observed a close
      correlation between the severity of tubular atrophy and tubulointerstitial
      fibrosis with the rate of tubular apoptosis (r=0.970, R2 =0.941, P< or =0.001).
      CONCLUSIONS: We have shown a time-dependent increase in apoptosis and PCNA
      antigen positive staining in the sub-total nephrectomy model of chronic renal
      failure correlating with the progression of renal fibrosis. PCNA staining did not
      match analysis for mitosis and was considered to overestimate the number of
      proliferating cells in the tissue. With this reservation in mind and taking into
      account the relative time-frames in vivo of apoptosis and proliferation;
      apoptosis potentially outweighs proliferation by a factor of 2 8-fold, when
      examined over the same time period. Consequently, even small changes in the
      finite numbers of apoptotic cells become highly significant. Our results have
      shown the definite role of apoptosis within progression of renal damage and
      highlighted how it may contribute to the progression of tubular atrophy and play
      a role in the pathogenesis of tubulo-interstitial scarring.

PMID- 9761501
TI  - Fosinopril ameliorates exogenous cholesterol-induced incipient glomerular lesions
      in obese Zucker rats. Effects on eicosanoid secretion.
AB  - BACKGROUND: To date, the role of dietary cholesterol as a risk factor for some
      diabetic nephrophathy, such as mesangial expansion and glomerular lesions, is
      unknown. Controversy also exists regarding the effects of prostaglandin-induced
      changes in glomerular haemodynamics on the appearance of glomerulosclerosis.
      METHODS: We have used obese Zucker rats (OZRs) as a model of early nephrophathy
      to evaluate the effect of hypercholesterolaemic diet on glomerular prostaglandin
      secretion and on the development of glomerular lesions. Due to the role of
      angiotensin II (Ang II) in glomerular haemodynamics, we have also evaluated its
      effects on glomerular eicosanoid secretion. Furthermore, as it has been suggested
      recently by clinical studies that angiotensin-converting enzyme inhibitors
      (ACEIs) reduce serum lipids associated with proteinuria, we have also evaluated
      the effect of the ACEI, fosinopril, both in vivo and in vitro, using 24 h
      glomeruli cultures. RESULTS: Results showed that a cholesterol-rich diet
      significantly increased serum cholesterol, proteinuria and glomerular eicosanoid
      secretion, and caused macrophage-ED1 cell deposits in the glomerular mesangium.
      Segmentary lesions only appeared in those rats with the highest percentage of
      glomerular xanthomatous (macrophage-ED1) cells. Ang II, per se, caused a marked
      rise in glomerular prosaglandin E2 and thromboxane B2. The inhibition of Ang II
      synthesis with fosinopril reduced all the parameters listed above, whereas Ang II
      (10(-6)M) increased the secretion of TxB2 and tended to increase PGE2 secretion
      in glomerular culture. CONCLUSIONS: In conclusion, exogenous cholesterol per se
      may contribute to nephropathy by increasing eicosanoid secretion, serum lipid
      profile, urinary protein excretion and the development of glomerular lesions.
      Fosinopril reduced all these parameters probably by its effects on Ang II.

PMID- 9761502
TI  - Effects of testosterone on glomerular growth after uninephrectomy.
AB  - BACKGROUND: Renal functional prognosis is consistently more adverse in male
      individuals with renal disease. Male animals develop more marked proteinuria and
      glomerulosclerosis in several models of renal damage. Renal and glomerular growth
      are important permissive factors for progression of renal failure. PURPOSE OF THE
      STUDY: To investigate the influence of testosterone on renal and glomerular
      growth. DESIGN: Renal compensatory growth after uninephrectomy (UNX) was chosen
      as a model of renal growth. The effect of testosterone was assessed in control
      male, in orchidectomized (OX) male, and in ovariectomized (OV) female SD rats.
      Observation time was 10 months. MEASUREMENTS: Albuminuria by nephelometry;
      glomerular diameter, glomerular tuft area, renal zonal analysis by quantitative
      stereology. Testosterone and dihydroxytestosterone by gas chromatography and RIA.
      RESULTS: In sham-operated male rats, testosterone administration did not change
      the (left) kidney:body-weight ratio after uninephrectomy. In contrast, in OX male
      rats, testosterone administration caused a significant increase in kidney:body
      weight ratio and in albuminuria. In these animals, glomerular diameter and outer
      stripe width were significantly lower in OX rats than in sham-operated controls.
      Glomerular volume and outer stripe width in OX animals were significantly higher
      after uninephrectomy (UNX) and were further increased in OX-UNX animals by
      administration of testosterone. Similar effects on glomerular diameter, cortical
      width (single) kidney:body-weight ratio were seen when OV female rats were
      treated with testosterone. CONCLUSION: After gonadal ablation, administration of
      testosterone amplifies compensatory glomerular and tubular growth in
      uninephrectomized male and female rats, i.e. testosterone is a permissive factor.
      Stimulation of glomerular growth may favour development of glomerulosclerosis.

PMID- 9761503
TI  - High-calcium intake abolishes hyperoxaluria and reduces urinary crystallization
      during a 20-fold normal oxalate load in humans.
AB  - BACKGROUND: The aim of the study was to test whether increasing dietary calcium
      intake lowers intestinal oxalate absorption and thereby prevents hyperoxaluria
      and urinary crystallization during a 20-fold normal oxalate load in healthy
      subjects. METHODS: Fourteen healthy male volunteers (age 23-44 years, BMI 21.5
      27.7 kg/m2) collected 24-h urines while on free-choice diet as well as on two
      standardized diets. The latter contained 2545 kcal, 2500 ml of mineral water, 102
      g of protein, 13.6 g of sodium chloride and 2220 mg of oxalate (approximately 20
      fold content of an average diet). Subjects were studied twice while on the
      standardized diet, once while eating a normal amount of calcium (1211 mg/day,
      oxalate-rich diet), and once while eating 3858 mg of calcium/day (calcium and
      oxalate-rich diet). RESULTS: Compared with the free-choice diet (322+/-36
      micromol/d), UOx x V increased to 780+/-72 micromol/d on the oxalate-rich diet
      (P=0.001) and fell again to 326+/-31 micromol/d on calcium and oxalate-rich diet
      (P=0.001 vs oxalate-rich diet). Urinary glycolate (a metabolic precursor of Ox)
      always remained below the upper limit of the normal range and did not change
      between different diets, indicating that changes in UOX x V reflect respective
      variations in intestinal absorption of Ox. Uca x V was 4.60+/-0.45 mmol/d on the
      free-choice diet and 3.20+/-0.32 mmol/d on the oxalate-rich diet (P=0.011 vs free
      choice diet); it increased to 7.28+/-0.74 mmol/d on the calcium- and oxalate-rich
      diet (P=0.001 vs free-choice and oxalate-rich diets). As indicated by the AP
      (CaOx) index (Tiselius), urinary supersaturation did not vary significantly
      between the three diets. In freshly voided morning urines (studied in 8/14
      subjects) on the oxalate-rich diet, CaOx crystals or crystal aggregates of up to
      80 microm diameter were found in 5/8 urines, whereas this never occurred on the
      free-choice diet and only t once on the calcium- and oxalate-rich diet.
      CONCLUSION: . Increasing calcium intake while eating Ox-rich food prevents
      dietary hyperoxaluria and reduces CaOx crystallization in healthy subjects. This
      further illustrates that dietary counseling to idiopathic calcium-stone formers
      should ensure sufficient calcium intake, especially during oxalate-rich meals.

PMID- 9761504
TI  - Adverse effects of chronic low level lead exposure on kidney function--a risk
      group study in children.
AB  - BACKGROUND: Children have been considered a risk group for lead (Pb) toxicity,
      mainly because of neurophysiological or neuro-cognitive deficits following Pb
      exposure. Blood Pb levels (b-Pb) of 100 microg/l currently have been defined as
      the lowest adverse effect level. The aim of this study was to compare, with the
      help of urinary markers, the kidney function of children with b-Pb just above
      this threshold with that of unexposed children, to assess from a nephrological
      point of view whether the current threshold is justified and whether children
      really are a particularly vulnerable risk group in terms of Pb-induced kidney
      damage. METHODS: In a cross-sectional study, 112 children, either from unexposed
      areas (controls, n=50) or Pb-contaminated areas (n=62), the latter partly with a
      known history of elevated b-Pb, were examined. Twenty nine urinary or serum
      markers mostly related to the function or integrity of specific nephron segments
      were determined (e.g. filtered plasma proteins, tubular enzymes, tubular
      antigens, eicosanoids). RESULTS: b-Pb were 39+/-13 microg/l in controls and 133+/
      62 microg/l in exposed children. The main findings were increased excretion rates
      of prostaglandins and thromboxane B2, epidermal growth factor, beta2
      microglobulin and Clara cell protein in the exposed children. A relationship
      between b-Pb and the prevalence of values above the upper reference limits was
      observed. CONCLUSIONS: With the help of urinary markers, nephron segment-specific
      effects of chronic low-level Pb exposure could be detected in children. The
      pattern of effects on glomerular, proximal and distal tubular and interstitial
      markers was similar to that previously observed in adults. The changes, however,
      occur at lower b-Pb levels than in adults. The current threshold appears to be
      justified also from a nephrological point of view, and children can indeed be
      considered a special risk group.

PMID- 9761505
TI  - Diurnal blood pressure variation and albuminuria in normotensive patients with
      insulin-dependent diabetes mellitus.
AB  - BACKGROUND: Abnormalities of the systemic blood pressure are closely associated
      with the development of diabetic nephropathy. Our aim was to examine the
      relationship between diurnal blood pressure pattern and albuminuria in insulin
      dependent normotensive diabetic patients before the development of overt
      nephropathy. METHODS: Urinary albumin excretion rates were determined by
      radioimmunoassay, and 24-h ambulatory blood pressure monitoring was performed.
      Means and diurnal index was calculated for systolic, diastolic and mean arterial
      blood pressure, for day-time, night-time, and the whole day. The results of the
      normoalbuminuric (n = 39) and microalbuminuric (n = 29) groups are compared, and
      correlation of the blood pressure parameters with albuminuria is analysed.
      RESULTS: Twenty-four hours and night-time mean blood pressures were significantly
      higher, diurnal indices characterizing the night-time blood pressure drop were
      smaller in the microalbuminuric group. With multiple regression analysis a
      significant positive correlation was found between albumin excretion rates and 24
      h mean systolic blood pressure and a significant negative correlation between
      albumin excretion rates and the diurnal index of mean arterial pressure (r2=
      0.40, P<0.0001). In the normoalbuminuric group 1 (2.6%) patient, in the
      microalbuminuric group 7 (24.1%/) were 'non-dippers'. CONCLUSION: We conclude
      that in normotensive insulin-dependent diabetic patients the night-time decrease
      of blood pressure is smaller if microalbuminuria is present. Higher nocturnal
      blood pressure load is associated with the increase of albuminuria, even before
      the onset of overt diabetic nephropathy or hypertension.

PMID- 9761506
TI  - Renal haemodynamic responses to a chicken or beef meal in normal individuals.
AB  - BACKGROUND: In normal subjects, protein loading with soybean meal does not
      produce the same renal haemodynamic effects as those observed with a beef meal.
      The renal responses of an acute protein load in the form of chicken meal is
      unknown. METHODS: To examine whether the renal response to a chicken meal differs
      from that to beef, we studied the renal function of eight normal healthy
      volunteers before and after a protein load with each of these meals. In a
      crossover randomized study, we measured the glomerular filtration rate (GFR;
      inulin clearance), renal plasma flow (RPF; para-aminohippurate clearance) and,
      plasma amino acid and glucagon levels. We also determined the amino acid content
      of a sample of chicken and beef. RESULTS: GFR and RPF increased significantly 2 h
      after both the chicken and beef meals (chicken, 98+/-13 vs 119+/-18 and 476+/-123
      vs 570+/-99 ml/min/1.73 m2; beef, 107+/-14 vs 122+/-16 and 501+/-118 vs 560+/-97
      ml/min/1.73 m2, for GFR and RPF at basal and 2 h respectively, P<0.05). Renal
      vascular resistance decreased and the filtration fraction remained unchanged
      after both protein loads. The changes induced by the protein challenges in the
      plasma amino acid and glucagon levels were not different between the two protein
      sources. The amino acid contents of chicken and beef samples were similar.
      CONCLUSION: In normal subjects, chicken and beef meals induced a similar degree
      of hyperfiltration.

PMID- 9761507
TI  - Optimal design of a two-sample test for assessing [125I]iothalamate plasma
      clearance in peritoneal dialysis.
AB  - BACKGROUND: Plasma clearance of a tracer in peritoneal dialysis (PD) can be used
      to assess treatment adequacy without labour-intensive fluid collections. Accuracy
      and precision of plasma clearance estimates by the bolus injection technique
      depend on the estimation accuracy of the area under the concentration curve and
      the measurement precision of plasma concentrations. The first source of error is
      due to oversimplified, e.g. monoexponential, descriptions of plasma disappearance
      curves. The second source of error arises from the propagation of measurement
      errors to the parameter estimates. METHODS: The theoretical bias of parameter
      estimates is determined first for a monoexponential approximation of a
      biexponential disappearance curve and as a function of the first sampling time at
      which mixing is still incomplete. The precision of plasma clearance estimates,
      expressed as coefficient of variation, is then described as a function of the
      experimental variables and of the standard deviation of measurement error. This
      allows the determination of the optimal two-sample test that yields most precise
      estimates of plasma clearance. RESULTS: The optimal two-sample schedules for
      assessing plasma clearance of [125I]iothalamate in PD patients vary between
      subjects according to individual clearances and distribution volumes. Our results
      suggest collecting the first sample 120 min, and the second 2-4 days, after the
      bolus injection. CONCLUSIONS: The proposed two-sample test is suitable to be used
      in clinical routine for assessment of adequacy of PD treatment but requires a
      priori estimation of individual tracer kinetics and of laboratory measurement
      errors. A fixed design with the first sample taken after 120 min and the second
      sample collected 3 days after the bolus injection should yield the best
      performance.

PMID- 9761508
TI  - Hyperleptinaemia of end-stage renal disease is corrected by renal
      transplantation.
AB  - BACKGROUND: Previous studies have reported that patients with end-stage renal
      disease (ESRD) have elevated plasma leptin concentrations, but the cause and
      significance of the elevations are unknown. We studied leptin concentrations in
      29 adults undergoing renal transplantation, to determine if restoration of renal
      function reduced leptin concentrations in ESRD. METHODS: Leptin concentrations
      were measured by radioimmunoassay in plasma specimens collected within 1 week
      before transplant, 6 days post-transplant, and 60 days post-transplant. RESULTS:
      Mean plasma leptin concentrations were higher in both male and female ESRD
      patients compared with a control population of similar age and body mass index
      (BMI), but most of the disparity was due to a minority of patients with grossly
      elevated concentrations; the majority of ESRD patients had normal or near-normal
      leptin concentrations after accounting for their adiposity with BMI. Six days
      after successful renal transplantation, average plasma leptin concentrations
      decreased to control levels. The grossly elevated pretransplant concentrations in
      a minority of patients were greatly reduced in relation to BMI, and the reduction
      persisted to 60 days post-transplant. The decrease in creatinine with transplant
      did not correlate with the decrease in leptin. CONCLUSIONS: These results
      demonstrate that restoration of renal function in ESRD patients reduces
      hyperleptinaemia, which provides further evidence of a cause/effect relationship
      between impaired renal function and abnormal leptin metabolism.

PMID- 9761509
TI  - Plasma leptin concentration in kidney transplant patients during the early post
      transplant period.
AB  - BACKGROUND: Leptin, is produced by adipose tissue and is presumed to be involved
      in the regulation of appetite and energy balance. The kidneys are involved in the
      inactivation of circulating leptin, and elevated plasma leptin concentrations
      were reported in uraemic patients. Finally, glucocorticosteroids as used in
      transplanted patients stimulate leptin secretion. METHODS: The present study
      aimed to asses the relationship between plasma leptin concentration and kidney
      graft function in the early post-transplant period. We studied 40 successfully
      transplanted haemodialysed uraemic patients (27 males, 13 females, mean age 34.3
      +/- 1.6 years, mean body mass index 22.5 +/- 0.5 kg/m2). The circadian rhythm of
      leptinaemia and insulinaemia was assessed twice: 2-4 days after kidney
      transplantation and 1 day before discharge from the hospital when graft function
      was good. Plasma leptin concentration was measured at 8 am, 4 pm, and 12 pm. The
      control group consisted of 21 healthy subjects (13 males, 8 females, mean age
      39.4+/-2.5 years, mean body mass index 24.1 +/-0.7 kg/m2). RESULTS: Before kidney
      transplantation, patients had elevated plasma leptin and insulin levels. A
      positive correlation was found between BMI and leptinaemia and BMI and
      insulinaemia, respectively. An inverse relationship was found between leptinaemia
      and age. Successful kidney transplantation was followed by a significant decline
      of leptinaemia i.e. from 21.5 +/- 0.1 vs 7.1 +/- 1.3 ng/ml. Kidney
      transplantation did not influence the circadian rhythm of leptinaemia.
      CONCLUSION: Leptinaemia was not related to the excretory graft function or
      immunosuppression. In addition to renal excretory function, other factors must be
      involved in the post-transplant decline of leptinaemia.

PMID- 9761510
TI  - Low-density lipoprotein subfraction profiles in chronic renal failure.
AB  - BACKGROUND: Small low-density lipoprotein (LDL) particle size, a newly recognized
      risk factor for cardiovascular disease in the general population, is frequently
      associated with hypertriglyceridaemia, the predominant plasma lipid abnormality
      present in uraemia. METHODS: Plasma lipids and LDL subfraction profiles were
      examined in 33 non-dialysed patients with chronic renal failure (predial), 40
      patients on continuous ambulatory peritoneal dialysis (CAPD), 42 haemodialysis
      patients (HD), 47 renal transplant recipients (RTR), and 44 controls. LDL
      subfractions separated by gel electrophoresis were scored by densitometric
      analysis (higher scores indicate profiles comprising smaller particles). RESULTS:
      All groups with renal failure had significantly elevated (mean+/-SD) LDL scores
      (predial 1.36+/-0.6, CAPD 1.71+/-0.9, HD 1.68+/-0.9, RTR 1.92+0.8 vs control
      0.87+0.4, all P<0.001), this being the only lipid abnormality detected in the
      predialysis patients. In CAPD and HD patients, LDL scores were associated with
      serum triglyceride (r=0.81, P<0.001 and r=0.70, P<0.001 respectively),
      cholesterol (r=0.55, P<0.001 and r=0.49, P<0.01) and HDL-cholesterol (r= -0.43,
      P<0.01 and r= -0.51, P<0.01), whilst no such relationship was seen in the
      predialysis and RTR groups, suggesting that other factors were important.
      CONCLUSIONS: The presence of small LDL particles appears to be an early and
      unexplained feature of the uraemic dyslipidaemia. This abnormality persists after
      renal transplantation and may represent an important atherogenic risk factor.

PMID- 9761511
TI  - In vivo and in vitro neurotoxic action of plasma ultrafiltrate from uraemic
      patients.
AB  - BACKGROUND: In order to investigate the aetiology of uraemic neuropathy, we
      evaluated the neurotoxic activity of plasma from uraemic patients. To this end we
      prepared a concentrate (1:1000) of 2-60 kDa MW compounds from paired filtration
      dialysis ultrafiltrate and evaluated its activity on peripheral nerve conduction
      in vivo and in vitro. METHODS: The in vivo neurotoxicity was tested on rat
      sciatic nerve by intraneural injection of the uraemic concentrate, followed, 1 to
      6 days later, by electrophysiological assessment of motor response and maximum
      conduction velocity. In vitro experiments were performed on isolated frog sciatic
      nerve in the presence of uraemic concentrate, and the neurotoxicity was evaluated
      from the rate of the decrease in the amplitude of the evoked maximal action
      potential. RESULTS: In the in vivo experiments, the sciatic nerves injected with
      the uraemic concentrate showed a decrease in maximum conduction velocity and a
      progressive impairment in evoked motor response. In the in vitro experiments
      uraemic concentrate induced a dose-dependent neurotoxic effect. CONCLUSIONS: Our
      study demonstrates the presence in plasma of uraemic patients of a compound of 2
      60 kDa MW with neurotoxic activity.

PMID- 9761512
TI  - Bone markers in the diagnosis of low turnover osteodystrophy in haemodialysis
      patients.
AB  - BACKGROUND: Renal osteodystrophy includes a number of low and high turnover bone
      histologic patterns which require a bone biopsy for their full identification.
      The role of intact PTH and several classical and more recent bone markers in the
      non-invasive diagnosis of renal bone disease in patients with CRF in HD requires
      further definition since available published data are limited. METHODS: In
      addition to intact PTH, alkaline phosphatase (AP) and osteocalcin (BGP), bone
      alkaline phosphatase isoenzyme (BALP), tartrate resistant acid phosphatase
      (TRAP), C-terminal cross-linked peptide of collagen type 1 (ICTP) and
      deoxypyridinoline (DPD) were measured in the serum of 41 patients on
      haemodialysis, subjected at the same time to transiliac bone biopsy for
      histomorphometric, histodynamic and aluminium histochemical examination.
      Histodynamic evaluation following double tetracycline label, was carried out in
      37 patients. The patients had no evidence of active cytolytic and cholestatic
      liver disease and a history of very limited aluminium exposure. RESULTS: The
      patients had differing degrees of hyper-parathyroidism, with intact PTH ranging
      from normal to very elevated levels. Serum values of the markers BGP, ICTP and
      DPD, normally excreted through the kidneys, were on average very high. The
      correlation coefficients of the humoral parameters vs dynamic variables, such as
      BFR/BS, were high. The highest values were: intact PTH 0.798, AP 0.900, BALP
      0.891, ICTP 0.807. The patients, grouped in low turnover osteodystrophy (LTO; 9),
      mixed osteodystrophy (MO; 9) and prevalent hyperparathyroidism (HP; 23), showed
      significant difference in the levels of most humoral and static and dynamic
      parameters (ANOVA). Bone aluminium histochemistry was negative in all cases.
      Discrimination of LTO patients from the other groups by humoral parameters, at
      the highest value of accuracy, showed 100% sensitivity and 93.7% specificity with
      a cut-off of 12.9 ng/ml for BALP; 88.9% sensitivity and 93.7% specificity with a
      cut-off of 21.5 ng/ml for DPD, and 88.9% sensitivity and 90.6% specificity with a
      cut-off of 79.7 pg/ml for intact PTH. The other markers had lower values. A
      standardized z-score approach for evaluation of all humoral parameters was also
      carried out. Using all variables, a correct classification of MO/HP and of LTO
      was possible in 93.8 and 88.9% of the cases, respectively. Predictive power was
      96.8 and 80%, respectively for MO/HP and LTO. When the only variables used were
      intact PTH and BALP, a correct classification of MO/HP and LTO was possible in
      90.6% and 88.9%, respectively. Predictive value of MO/HP was 96.7% and for LTO
      72.7%. Predictive values using PTH and AP were 96.3% and 57.2%, respectively.
      CONCLUSION: Intact PTH and several relatively new bone markers are of certain
      value in the non-invasive diagnosis of renal osteodystrophy. However some of the
      humoral markers carry the same quality of information and the use of intact PTH
      and BALP may be adequate in the discrimination of bone histologic patterns. In
      cases exempt from liver disease, PTH and AP may be used as a less costly
      alternative. Bone biopsy could be chiefly limited to cases with borderline
      humoral values and to all those with a suspected aluminium overload.

PMID- 9761513
TI  - Effect of RenaGel, a non-absorbed, calcium- and aluminium-free phosphate binder,
      on serum phosphorus, calcium, and intact parathyroid hormone in end-stage renal
      disease patients.
AB  - BACKGROUND: Control of dietary phosphate absorption in end-stage renal disease
      patients is essential to prevent the deleterious sequelae of phosphorus
      retention. Efficacy of currently available calcium- and aluminium-containing
      phosphate binders is constrained by the side-effects associated with the
      absorption of calcium and aluminium. The current study examined the efficacy of
      RenaGel, a calcium- and aluminium-free, polymeric phosphate binder, in end-stage
      renal disease patients. METHODS: Administration of calcium- or aluminium
      containing phosphate binders ceased during a 2-week washout period. RenaGel, at
      starting doses of one, two, or three 500-mg capsules three times per day with
      meals, was administered for 8 weeks. RenaGel dose was titrated up 1 capsule per
      meal at the end of each 2-week period if necessary to achieve phosphorus control.
      A second 2-week washout period followed the end of RenaGel treatment. RESULTS:
      Mean serum phosphorus rose from a pre-washout level of 6.9 mg/dl (2.23 mmol/l) to
      8.1 mg/dl (2.62 mmol/l) at the end of the initial 2-week washout. With RenaGel
      treatment, serum phosphorus declined and returned to pre-washout levels after 4
      weeks. Serum phosphorus reached a nadir of 6.5 mg/dl (2.10 mmol/l) after 7 weeks
      of RenaGel treatment. Serum phosphorus rose to 8.2 mg/dl (2.65 mmol/l) 2 weeks
      after cessation of RenaGel treatment. As anticipated, calcium declined during the
      initial washout period when calcium-based phosphate binders were stopped for the
      majority of patients. The rise in serum phosphorus and decline in serum calcium
      during washout resulted in an increase in median intact parathyroid hormone
      (iPTH) levels from 292 pg/ml to 395 pg/ml. iPTH fell to 283 pg/ml after 6 weeks
      of RenaGel treatment despite a persistently lower serum calcium. RenaGel
      treatment also reduced serum total and LDL cholesterol by 25 mg/dl (0.65 mmol/l)
      and 23 mg/dl (0.59 mmol/l) respectively. CONCLUSIONS: RenaGel appears to be an
      effective phosphate binder free of calcium and aluminium. Phosphorus control with
      two to four RenaGel capsules per meal appears to result in comparable phosphorus
      lowering seen with calcium- or aluminium-based phosphate binders. RenaGel may
      offer an alternative for the control of phosphorus retention in end-stage renal
      disease patients.

PMID- 9761514
TI  - Haemodialysis dose is independent of type of surgically-created vascular access.
AB  - BACKGROUND: In the United States, the use of polytertraflouroethylene (PTFE)
      graft compared with native arteriovenous fistula (AVF) for haemodialysis vascular
      access has been increasing despite a greater than twofold higher incidence of
      thrombosis and infection associated with PTFE grafts. METHODS: We studied 214
      haemodialysis patients with not more than two revisions of their vascular access,
      to determine whether any relationship exists between the type of haemodialysis
      vascular access and dialysis dose assessed primarily by urea reduction ratio (per
      cent reduction in blood urea nitrogen concentration after a dialysis session).
      Serum albumin concentration was used as a secondary outcome measure of dialysis
      adequacy. Urea reduction ratio and predialysis serum albumin concentration were
      measured at onset of study and at 4-week intervals and mean values were
      calculated for each subject. RESULTS: The 214 patients (118 males, 96 females)
      included 173 Blacks (81%), 26 Whites (15%), and 15 Hispanics (7%), of mean (+/
      SD) age 55.6+/-15.5 years. Of these 214 subjects, 111 (52%) had a native AVF,
      while 103 (48%) had a PTFE graft. Both mean urea reduction ratio (native AVF=69
      +/-6.7% vs PTFE graft=70+/-7.3%; P=0.31), and mean serum albumin concentration
      (native AVF=4.02+/-0.39 g/dl vs PTFE graft=4+/-0.33 g/dl; P= 0.59) were
      equivalent in both groups. Separate multiple logistic regression analyses with
      type of vascular access as one of the independent variables, found no significant
      relationship between type of vascular access and either a urea reduction ratio >
      65% (P= 0.67), or a serum albumin concentration >4g/dl (P=0.89), after adjustment
      for age of vascular access, access revision, location of access, dialyser urea
      clearance, length of dialysis treatment, body weight, and age. CONCLUSION: We
      conclude that PTFE grafts do not permit delivery of better dialysis than native
      AVF. The increasing use of PTFE grafts in the United States does not have any
      clinical justification.

PMID- 9761515
TI  - Acute effects of haemodialysis on cutaneous microcirculation in patients with
      peripheral arterial occlusive disease.
AB  - BACKGROUND: Peripheral arterial occlusive disease (PAOD) is an increasing problem
      in patients on maintenance haemodialysis. Alterations in microvascular perfusion
      accompany and complicate arteriosclerosis of large vessels and might contribute
      to the disease process. The aim of the study was to investigate the acute effects
      of haemodialysis on the cutaneous microcirculation in 26 patients with and
      without intermittent claudication. METHODS: Cutaneous perfusion was assessed by
      measuring transcutaneous oxygen pressure (tcPO2) and skin temperature at the
      dorsum of the foot. After standardized cooling to 15 degrees C of a 2cm2 skin
      area, the time to reach baseline skin temperature was evaluated as an indirect
      parameter of reactive hyperaemia. RESULTS: During haemodialysis, tcPO2 dropped
      significantly in both groups. The decrease in tcPO2 was more pronounced in
      patients with PAOD (20% vs 15% n.s.). The reactive hyperaemia response was
      reduced significantly in patients with intermittent claudication indicated by a
      prolonged time to reach baseline skin temperature after cooling. Values of tcPO2
      and reactive hyperaemia did not reach baseline values at the end of haemodialysis
      in either group. CONCLUSIONS: Nutritive skin perfusion is impaired during
      haemodialysis. These changes are more pronounced in patients with PAOD and
      persist after dialysis. These findings are relevant for the treatment of patients
      with vascular disease on maintenance haemodialysis.

PMID- 9761516
TI  - Renal insufficiency after heart transplantation: a case-control study.
AB  - BACKGROUND: In Rotterdam 304 heart transplants have been performed since 1984.
      End-stage renal failure, necessitating renal replacement therapy, has developed
      in 24 patients (8%) after an interval of 25-121 months (median 79 months). After
      starting renal replacement therapy one-year survival was only 60%. Overall
      survival after heart transplantation, however, was favourable: 5 and 10 year
      survival rates of 79% and 50% respectively. METHODS: A case-control study was
      performed to identify possible risk factors in cases who went on to develop end
      stage renal failure compared to controls. RESULTS: We found that renal failure
      was not limited to elderly patients with ischaemic heart disease, but also
      occurred in young patients having dilated cardiomyopathy. A significant rise in
      the serum creatinine was found in cases compared to controls as early as 3 months
      after transplantation. Cyclosporin dose and trough levels were not different
      between cases and controls. Neither were there differences in the use of calcium
      antagonists or other antihypertensive drugs, allopurinol or diuretics. Rejection
      incidence was also similar between the two groups. CONCLUSIONS: Renal failure
      after heart transplantation is a long term complication of cyclosporin use that
      is not limited to elderly patients with ischaemic heart disease. Cyclosporin dose
      and trough levels in the cases were not different from patients maintaining
      stable good renal function, indicating that cyclosporin nephrotoxicity is the
      result of an individually determined susceptibility to cyclosporin. Suggestions
      for future strategies to prevent renal failure are given.

PMID- 9761517
TI  - The effect of felodipine on renal function and blood pressure in cyclosporin
      treated renal transplant recipients during the first three months after
      transplantation.
AB  - BACKGROUND: Due to their vasodilatory effect, calcium antagonist may have a
      renoprotective against cyclosporin (CsA)-induced nephrotoxicity and rise in blood
      pressure (BP) seen in renal transplantation. METHODS: In order to evaluate the
      effect of the calcium antagonist felodipine on renal function and BP during
      cyclosporin treatment, 79 CsA-treated renal transplant recipients were
      investigated during the first 3 months after transplantation in a randomized,
      double-blind, placebo-controlled study with two parallel groups. Felodipine (ER
      tablets, 10 mg) or placebo was given prior to transplantation and each day during
      the study period. The patients were assessed twice, i.e. at 4-6 weeks and at 10
      12 weeks after transplantation. Renal plasma flow (RPF) and glomerular filtration
      rate (GFR) were measured by constant infusion technique. Tubular function was
      estimated from clearance of lithium. RESULTS: At 6 weeks after transplantation,
      felodipine caused a significantly higher RPF [felodipine: 219 +/- 70 ml/min;
      placebo: 182+/-56 ml/min (mean+/-1 SD); P=0.03]. No differences were found in
      GFR, filtration fraction (FF), tubular sodium handling, or sodium excretion.
      Felodipine lowered BP significantly. At 12 weeks after transplantation,
      felodipine caused a significantly higher GFR (felodipine: 49+/-18 ml/min;
      placebo: 40+/-16 ml/min; P=0.05) and RPF (felodipine: 225+/-77 ml/min; placebo:
      175+/-48 ml/min; P<0.01). No difference was found in FF. Felodipine lowered BP
      significantly. No differences were found with regard to duration of primary
      anuria, hospitalization time, number of rejection episodes, plasma creatinine day
      7 post-transplant, or treatment doses of CsA. CONCLUSIONS: It is concluded that
      in renal transplant recipients treated with CsA, felodipine significantly
      increased both GFR and RPF 3 months after transplantation when compared with
      placebo, despite a concomitant lowering of BP. A possible antagonizing affect of
      felodipine against CsA-induced nephrotoxicity in these patients is suggested.

PMID- 9761518
TI  - Automated peritoneal dialysis: a Spanish multicentre study.
AB  - BACKGROUND: A prospective sequential study on continuous ambulatory peritoneal
      dialysis (CAPD) and three techniques of automated peritoneal dialysis (APD) was
      conducted to assess peritoneal clearances, the influence of peritoneal
      permeability on nocturnal APD clearances and the suitability of the peritoneal
      equilibration test (PET) for predicting clearances on APD. METHODS: After
      performing a PET, a series of clinical, biochemical and dialysis adequacy markers
      were evaluated after 2 months on CAPD, continuous cycling peritoneal dialysis
      (CCPD) and tidal volume peritoneal dialysis (TPD) with 50% and 25% tidal volumes.
      Forty five patients participated and 33 completed the study. RESULTS: Serum urea
      and creatinine decreased significantly whereas haemoglobin and glucose increased.
      Mean peritoneal urea clearance (1/week) was 55.40+/-8.76 on CAPD, 74.82+/-12.62
      on CCPD, 69.20+/-14.63 on TPD (tidal 50%) and 66.89+/-13.23 on TPD (tidal 25%);
      mean creatinine clearance (1/week/1.73 m2) was 42.80 +/- 9.95, 52.19 +/- 11.11,
      51.31 +/- 13.3 and 49.17 +/- 11.83, respectively. Both clearances were
      significantly lower on CAPD than on APD (P<0.001). CCPD was the automated
      technique that provided the best nocturnal urea clearance (P<0.01). Nocturnal
      creatinine clearance did not show significant differences between CCPD and TPD
      (tidal 50%), being better with both techniques than with TPD (tidal 25%). There
      were statistically significant differences between nocturnal dialysate to plasma
      (D/P) ratios and those corresponding to the nearest times in the PET. The urea
      D/P ratio at 180 min and the creatinine D/P ratio at 240 min of the PET were the
      parameters that better estimated nocturnal clearances on APD. CONCLUSIONS: This
      study confirms that TPD does not improve the results of CCPD. Significant
      differences between D/P ratios during actual nocturnal cycles and PETs were
      observed.

PMID- 9761519
TI  - Icodextrin use in CCPD patients during peritonitis: ultrafiltration and serum
      disaccharide concentrations.
AB  - BACKGROUND AND METHODS: In a randomized study on the biocompatibility of
      icodextrin (I) versus glucose (G) in CCPD we used icodextrin or glucose for the
      long daytime dwell. During the night-time dwells glucose was used in all
      patients. In case of peritonitis icodextrin was continued. In all patients
      ultrafiltration (UF) was recorded and serum icodextrin metabolites were
      determined every 3 months and during peritonitis in I-users when available.
      RESULTS: Thirty-eight patients ( 19 G, 19 I) entered the study and suffered 30
      peritonitis episodes (16 G, 14 I). During peritonitis (P), daytime dwell UF
      decreased significantly in G (P=0.001), but remained stable in I patients
      compared to non-peritonitis (NP) episodes. Total 24-h UF decreased in G (P=0.001)
      and in I patients (P=0.04), as the result of a decreased daytime UF and night
      time UF, respectively. There was no difference in the used glucose concentrations
      during the P versus NP episodes. In five I-patients serum disaccharides increased
      from 0.05+/-0.01 to 1.26+/-0.23mg/ml during follow up. During peritonitis serum
      disaccharide concentrations did not increase further (1.47+/-0.24 mg/ml, P=
      0.56). In I patients total carbohydrate minus glucose rose to 5.72 +/- 1.2 mg/ml
      during follow up, and to 6.63 +/- 1.04 mg/ml during peritonitis (P=0.7). These
      concentrations are comparable to CAPD patients despite the longer dwelltime in
      CCPD (8-10 versus 14-16 h, respectively). Adverse reactions attributable to
      icodextrin were not encountered. CONCLUSIONS: In contrast to glucose, icodextrin
      preserved the daytime dwell ultrafiltration during peritonitis. Serum icodextrin
      metabolites increased during icodextrin use, but remained stable during
      peritonitis. Adverse effects were not observed.

PMID- 9761520
TI  - Lipid profile in haemodialysis patients treated with recombinant human
      erythropoietin.
AB  - BACKGROUND: The long-term effect of recombinant human erythropoietin (rhEPO) on
      the blood-lipid profile has not been well documented. The aim of this study was
      to evaluate whether rhEPO therapy affects the lipid pattern. METHODS: A group of
      102 maintenance haemodialysis patients were treated for 2 years with rhEPO given
      intravenously at the end of the dialysis session. Attempts were made to keep the
      haemoglobin (Hb) at 10-11 g/dl and/or the haematocrit (Hct) at 30-35%. Twenty
      maintenance haemodialysis patients not treated with rhEPO were examined as
      controls. Total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides,
      apolipoproteins A1 and B, and lipoprotein (a)[Lp (a)] were assessed at baseline
      (without rhEPO), and 1 and 2 years after the beginning of treatment. Hb, Hct and
      ferritin were measured monthly, and Kt/v was evaluated monthly and kept above
      1.1. RESULTS: During follow-up, in both groups, there was a significant increase
      in Apo A1 and no significant changes in the other lipid parameters. In the
      treated group, Hb and Hct increased significantly after the fourth month of
      treatment. CONCLUSIONS: Erythropoietin therapy does not affect significantly the
      levels of total cholesterol, LDL- and HDL-cholesterol, triglycerides, Apo B and
      Lp (a) in maintenance hemodialysis patients.

PMID- 9761521
TI  - Peritoneal protein loss in children with nephrotic syndrome during peritoneal
      dialysis.
AB  - BACKGROUND: The passage of proteins across the glomerular filtration barrier is
      mainly determined by the size of the protein. In nephrotic syndrome (NS) the
      glomerular permselectivity is affected, causing proteinuria. Some authors suggest
      the existence of a generalized basement membrane defect. The permeability
      characteristics of the peritoneal basement membrane in children with NS are not
      known. METHODS: The transperitoneal transport of proteins with a different
      molecular weight (beta2-microglobulin MW 11800 D, albumin MW 69000 D, IgG MW
      160000 D, and alpha2-macroglobulin MW 820000 D) was studied in a study group
      (group A) consisting of six stable nephrotic children (three with
      glomerulosclerosis and three with congenital nephrotic syndrome, one of them with
      mesangial sclerosis) and compared to a control group (group B) consisting of
      eight stable children on peritoneal dialysis. After a dwell of 6 h with Dianeal
      1.36% dialysate and serum samples were collected. For each patient the dialysate
      to plasma (D/P) ratios of the four proteins were calculated. The D/P ratios of
      the nephrotic patients in group A were compared to the D/P ratios of the patients
      in the control group B. Data were expressed as mean +/- SD. RESULTS: The values
      for the D/P ratios (in percentage) of beta2-microglobulin, albumin, IgG and
      alpha2-macroglobulin in group A were 19.6+/-9.9, 2.7+/-1.7, 1.6+/-0.9, and 0.5+/
      0.4, compared to 24.9+/-10.2, 4.0+/-2.3, 2.2 +/- 1.2, and 0.7 +/- 0.3 in the
      control group B. The ratios were plotted against MW on a double logarithmic
      scale. In all patients a linear relationship between molecular weight and D/P
      ratio of the proteins was obtained. The D/P ratios of the study group did not
      differ significantly from the control group. CONCLUSION: We conclude that the
      size selectivity of the capillary permeability is not affected in the peritoneal
      membrane in children with NS due to glomerulosclerosis and congenital nephrotic
      syndrome.

PMID- 9761522
TI  - Methylenetetrahydrofolate-reductase gene C677T variant and kidney-transplant
      survival.
AB  - BACKGROUND. Hyperhomocysteinaemia, a risk factor for atherosclerosis, is common
      in haemodialysis and renal-transplant patients. As atherosclerotic lesions in
      hyperhomocysteinaemia resemble those of chronic allograft injury, we examined the
      hypothesis that the C677T variant of the methylenetetrahydrofolate reductase
      (MTHFR) gene, which is linked to elevated plasma homocysteine levels in patients
      with renal failure, determines renal allograft survival. METHODS: DNA was
      prospectively collected from 336 patients undergoing renal transplantation in our
      clinic between 1988 and 1994 and their corresponding donors. Patient and
      allograft survival was analysed by blinded review of all case records over a
      follow-up period of 36 months. Additionally, we recruited 83 patients surviving
      with a functional kidney allograft for at least 10 years (mean: 156, range 120
      240 months). MTHFR-C677T genotype was determined by a PCR-RFLP technique. The
      influence of genotype on transplant survival was analysed by Kaplan-Meyer life
      table analysis and two-tailed global log-rank testing. RESULTS: Frequency of the
      MTHFR-C677T allele in the cohort group was identical in recipients (0.35) and
      donors (0.34), and comparable to that in the longterm allograft survivors (0.37).
      Furthermore, life-table analysis revealed a similar allograft survival over 36
      months between the genotype groups (CC 74%, CT 69%, TT 75%). Other risk factors
      including donor and recipient age, hypertension, body-mass index, and number of
      rejection therapies were evenly distributed between the different genotype
      groups. CONCLUSIONS: These findings do not support the hypothesis that the C677T
      variant of the MTHFR gene is an important determinant of renal-transplant
      survival.

PMID- 9761523
TI  - Acute renal failure in Henoch-Schonlein purpura due to interstitial haemorrhage
      of the kidney.

PMID- 9761524
TI  - Relapsing nephrotic syndrome in a patient with Kimura's disease and IgA
      glomerulonephritis.

PMID- 9761525
TI  - Prolonged acute renal failure after i.v. immunoglobulin therapy in the refeeding
      phase of anorexia nervosa.

PMID- 9761526
TI  - Severe renal failure and polyneuritis induced by foscarnet.

PMID- 9761527
TI  - Tolosa-Hunt syndrome in uraemic patients undergoing maintenance haemodialysis.

PMID- 9761528
TI  - The dialysed patient with both Castleman disease and Kaposi sarcoma.

PMID- 9761529
TI  - Diabetic muscle infarction: an unusual cause of leg swelling in a diabetic on
      continuous ambulatory peritoneal dialysis.

PMID- 9761530
TI  - Massive haemoperitoneum due to rupture of splenic infarct during CAPD.

PMID- 9761531
TI  - Isolated urinary aspergillosis in a renal transplant recipient.

PMID- 9761533
TI  - Acute renal failure due to severe Landry-Guillain-Barre syndrome.
AB  - BACKGROUND: Blood urea nitrogen (BUN) >60 mg/dl has been reported to occur
      commonly in patient's with severe Landry-Guillain-Barre syndrome. AIMS: To find
      out the cause for this high BUN we compared the renal function tests of 30
      consecutive cases with severe Landry-Guillain-Barre syndrome to those of 30
      controls. RESULTS: Acute renal failure occurred in seven patients with Landry
      Guillain-Barre syndrome and none of the control group. Acute renal failure was
      found more in cases with Landry-Guillain-Barre syndrome compared to controls
      (P=0.0049). Six out of seven cases with Landry-Guillain-Barre syndrome and acute
      renal failure had dysautonomia and became oliguric while being in a hypotensive
      state. Of 30 patients with Landry-Guillain-Barre syndrome seven cases died. From
      eight patients with dysautonomia six cases who had acute renal failure died. The
      mortality rate was higher in cases with dysautonomia and acute renal failure (P =
      0.0001 and 0.00001, respectively). Interestingly no glomerular disease was found.
      CONCLUSION: In conclusion acute renal failure can occur commonly in cases with
      severe Landry-Guillain-Barre syndrome particularly in those with dysautonomia,
      causing high mortality.

PMID- 9761532
TI  - Isolated cerebral aspergillosis without a portal of entry--complete recovery
      after liposomal amphotericin B and surgical treatment.

PMID- 9761534
TI  - The patient with a clotted PTFE graft developing fever.
AB  - Haemodialysis access graft infection is easily recognizable when local symptoms
      (warmth, swelling, pain, or drainage) predominate, and endocarditis is a well
      established complication of infected grafts. We report a case of bacterial
      endocarditis complicating silent infection in clotted haemodialysis access graft.
      It is suggested that, clotted non-functioning grafts may be the harbingers of
      silent infection, and should be suspected as the source of infection in every
      haemodialysis patient that presents with fever, even in the absence of clinical
      signs of graft site infection.

PMID- 9761535
TI  - The dialysis patient with persisting elevation of bone alkaline phosphatase after
      parathyroidectomy.

PMID- 9761536
TI  - A reflection on endoscopic resection.

PMID- 9761537
TI  - Segmental glomerulopathy of early rejection.

PMID- 9761538
TI  - Iatrogenic hyperkalaemia--points to consider in diagnosis and management.

PMID- 9761539
TI  - Bright's disease and albuminuria as seen by the famous neurologist Jean-Martin
      Charcot.

PMID- 9761540
TI  - Preservation of renal function: the spectrum of effects by calcium channel
      blockers.

PMID- 9761541
TI  - Systemic amyloidosis secondary to xantogranulomatous pyelonephritis.

PMID- 9761542
TI  - Exclusion of the uteroglobin gene as a candidate for fibronectin glomerulopathy
      (GFND)

PMID- 9761543
TI  - Nephrotic syndrome associated with chronic lymphocytic leukaemia.

PMID- 9761544
TI  - Recurrent ventricular tachycardia complicating atypical haemolytic-uraemic
      syndrome.

PMID- 9761545
TI  - Systemic lupus erythematosus and thrombocytopenic purpura in two members of the
      same family following hepatitis B vaccine.

PMID- 9761546
TI  - Interstitial nephritis and retinitis pigmentosa.

PMID- 9761547
TI  - Protein C administration in meningococcal septicaemia.

PMID- 9761548
TI  - Autosomal dominant polycystic kidney disease presenting with prolonged
      macrohaematuria and perinephric haematoma.

PMID- 9761549
TI  - Unmasking of thyrotoxicosis after initiation of regular haemodialysis treatment?

PMID- 9761550
TI  - Importance of dry-weight assessment in well-being, appetite, nutritional status,
      and anaemia correction in haemodialysis patients.

PMID- 9761551
TI  - Tissue factor pathway inhibitor and tissue factor in HD and CAPD.

PMID- 9761552
TI  - Audit of quality of hospital haemodialysis in Scotland. The Scottish Renal
      Registry.

PMID- 9761553
TI  - Delayed renal function and allograft survival: does the type of post transplant
      dialysis influence outcome?

PMID- 9761554
TI  - Discontinuing trimethoprim-sulfamethoxazole prophylaxis does not lead to
      increased risk of rejection in renal transplant patients with stable graft
      function.

PMID- 9761555
TI  - Transient hyperphosphatasaemia in a 7-year-old boy following renal
      transplantation.

PMID- 9761556
TI  - Three-dimensional analysis of cleft palate topology in newborn infants with
      reference to the cranial skeleton.
AB  - OBJECTIVE: To describe a method of determining the three-dimensional topology of
      the palatal crest relative to a reproducible anthropomorphic coordinate system in
      newborn infants with unilateral cleft palate. For this purpose, physical models
      of the maxilla and face were analyzed by computer morphometry. DESIGN: The study
      was limited to infants referred to the craniofacial center during the first 11
      days after birth. SETTING: The study was performed at a craniofacial center
      servicing a large geographic area. PARTICIPANTS: The method was applied to 12
      infants with unilateral cleft lip, alveolus, and palate (eight patients with left
      side clefts and four with right-side clefts). MAIN OUTCOME MEASURES: The three
      dimensional topology of the palatal crest referenced to an anthropometric
      coordinate system was the primary outcome measure. The anthropometric reference
      system is defined by the tragus points and the midpoint of a line connecting the
      endocanthia. RESULTS: The topology of the maxillary crests of the patients was
      characterized by considerable variability. The center of the premaxilla as
      defined by the attachment of the frenulum was frequently displaced by several
      millimeters from the midsagittal plane. The displacement was to the left in
      infants with right-side clefts and to the right in infants with left-side clefts.
      The premaxilla can be rotated by more than 30 degrees relative to the normal
      position. No significant retroposition of the minor segment as determined by the
      location of the tuber points was found. Several morphometric anomalies were found
      to be correlated linearly. CONCLUSIONS: We propose that the morphologic
      deviations are in part caused by the neuromotor activity of the tongue and of the
      interrupted M. orbicularis oris. The data can serve as the starting point for a
      longitudinal study of craniofacial development in children with cleft palate and
      for studies on the efficacy of different therapeutic approaches.

PMID- 9761557
TI  - Quantitative description of the morphology of the human palate by a mathematical
      equation.
AB  - OBJECTIVE: To derive a three-dimensional mathematical description of normal human
      hard tissue palatal size and shape. METHODS: The maxillary dental casts of 30
      adolescents free from respiratory problems, who had a complete (28 teeth)
      permanent sound dentition with normal occlusion, were studied. The x, y, z
      coordinates of several standardized palatal and dental landmarks were obtained
      with a computerized three-dimensional digitizer. Palatal landmarks were used to
      derive a mathematical equation of palatal shape in the frontal and sagittal
      planes. Palatal width, length, frontal and sagittal heights, and sagittal slope,
      as well as dental arch transverse and anteroposterior dimensions, were computed.
      RESULTS: Neither the size nor the shape of the palate was significantly
      influenced by gender. Only the intercanine distance was larger (p < .025) in
      males than in females. CONCLUSIONS: Data collected in the present investigation
      could represent a first database for the quantitative description of normal human
      palatal morphology in subjects with a complete permanent dentition.

PMID- 9761558
TI  - A retrospective comparison of craniofacial form in Northern Irish children with
      unilateral cleft lip and palate.
AB  - OBJECTIVE: This study evaluated the craniofacial form of a sample of Northern
      Irish children with unilateral cleft lip and palate (UCLP). The quality of the
      outcomes achieved was compared with the outcomes reported for the six centers
      involved in the European multicenter study (Mars et al., 1992; Molsted et al,
      1992). DESIGN: Retrospective analysis. PATIENTS: All children born with complete
      skeletal UCLP in Northern Ireland during the years 1983 to 1987. MAIN OUTCOME
      MEASURES: Cephalometric analysis was used to determine the craniofacial form and
      soft tissue profile. The quality of the dental arch relationships was
      independently assessed using the Goslon ranking system. RESULTS: The sample
      comprised 25 children with complete skeletal UCLP who had cephalometric
      radiographs and study casts recorded at a mean age of 9.4 years (range, 8 to 11
      years). Cephalometric analysis revealed no important skeletal differences between
      the Northern Irish UCLP children and the published results from the six Eurocleft
      centers. The soft tissue profile of the Northern Irish UCLP children was
      significantly more convex than the soft tissue profile recorded for center D in
      the Eurocleft study. The Goslon ranking system revealed that 18 (72%) of the
      Northern Irish UCLP children had good or satisfactory dental arch relationships.
      CONCLUSIONS: No clinically important differences were detected between the mean
      cephalometric skeletal parameters of the Northern Irish UCLP children and those
      published for the six cleft centers involved in the Eurocleft study. On average,
      the Northern Irish UCLP children were found to differ significantly from
      Eurocleft's center D in their soft tissue facial contour and sagittal lip
      profile. The quality of the dental arch relationships of the Northern Irish
      sample was between the best and the less good Eurocleft centers.

PMID- 9761559
TI  - HONC measures in 4- to 6-year-old children. Horii Oral Nasal Coupling Index.
AB  - OBJECTIVE: To collect normative data using Horii's Oral Nasal Coupling Index
      (HONC) from 4- to 6-year-old children without cleft palate to be used in the
      evaluation of young children with cleft palate. In addition, to determine whether
      HONC values in children are similar to those of adults and thus show that the
      HONC ratio successfully normalizes nasal accelerometric signals across age,
      gender, and vocal intensity. DESIGN: Measurement of accelerometric and acoustic
      signals from novel nasal and nonnasal utterances, which the children repeated
      after the experimenter. Measurements also included four sustained [m]
      productions, which were used to calibrate correction factors used to equate nasal
      and oral signals during a sustained [m] production. SETTING: Laboratory at a
      state university. PARTICIPANTS: Ten girls and 10 boys, aged 4 to 6 years, with
      normal speech, language, and hearing. RESULTS: Differences of 13 dB (HONC) were
      found to separate nasal from nonnasal sentences. No significant difference in
      HONC score was found across gender for nasal/nonnasal sentences and [m]
      productions. The correction factors generated during [m] calibration procedures
      did not differ between girls and boys. CONCLUSIONS: Horii Oral Nasal Coupling
      Index differences between nasal and nonnasal utterances appear to be valid and
      reliable measures in both children and adults for detection of disorders of nasal
      resonance.

PMID- 9761560
TI  - Electromyographic investigation of masticatory muscles in unilateral cleft lip
      and palate patients with anterior crossbite.
AB  - OBJECTIVE: To evaluate the characteristics of masticatory muscle activity in
      operated unilateral cleft lip and palate (UCLP) patients with anterior crossbite
      compared with normal individuals. SUBJECTS: Sixteen male and 13 female Chinese
      patients with UCLP and anterior crossbite. Fifteen male and 13 female Chinese
      individuals without cleft abnormalities served as a control group. DESIGN:
      Electromyographic activity of the masseter muscles and anterior temporalis
      muscles was recorded bilaterally in different mandibular positions using bipolar
      surface electrodes. RESULTS: Compared to noncleft controls, patients with UCLP
      demonstrated (1) higher activation levels of masseter and temporalis muscles in
      the rest position, (2) lower potential function of masseter and temporalis, (3)
      inharmonious activity of the masticatory muscles during mandibular border
      movement, (4) a higher asymmetry index of the masseter and temporalis muscles,
      and (5) longer silent periods of the two muscles. CONCLUSIONS: The function of
      masticatory muscles is different in patients with UCLP with anterior crossbite.
      Muscle function should be considered when evaluating cleft patients for
      orthodontic treatment and orthognathic surgery.

PMID- 9761561
TI  - Muscle fiber type distribution in the normal human levator veli palatini muscle.
AB  - OBJECTIVE: This study examined the muscle fiber type distribution within the
      normal adult levator veli palatini muscle. METHODS: Levator veli palatini muscle
      tissue was harvested from the palates of 12 (seven female, five male) adult
      noncleft cadavers. Adjacent sections were stained for adenosine triphosphatase at
      pH 10.4 or 4.2. After mounting, magnifying, and photographing, Type I versus Type
      II fiber types were differentiated by the intensity of, or by the inhibition of,
      staining of matched fibers at each pH level. Type I fibers stained light at pH
      10.4 and dark at pH 4.2, while Type II fibers stained light at pH 4.2 and dark at
      pH 10.4. MAIN OUTCOME MEASURES: The number of fibers counted for each specimen
      ranged from 60 to 616. The numbers of Type I and Type II stained fibers appearing
      in each muscle tissue sample were determined and expressed as a percentage of the
      total number of fibers identified. A few identified fibers could not be labelled
      as either Type I or Type II. RESULTS: The overall proportion of Type I fibers,
      averaged across all specimens, was 59.8%. Male specimens had 67.4% Type I fibers
      and 31.8% Type II fibers, while female specimens had 54.4% Type I fibers and
      44.4% Type II fibers. CONCLUSIONS: Observed fiber type distributions were similar
      to those reported for other articulatory muscles, but differed slightly from
      previously reported distributions for normal levator veli palatini. The
      distributions observed in this study provide a baseline against which to relate
      fiber type data from the levator veli palatini of cleft palates to the functional
      status of the velopharyngeal mechanism.

PMID- 9761562
TI  - Adverse outcomes following endoscopic repair of a fetal cleft lip using an ovine
      model.
AB  - OBJECTIVE: The purpose of this study was to determine if endoscopic techniques
      could be used to repair an epithelialized lip cleft with accuracy and with an
      outcome comparable to fetuses treated through an open hysterotomy. INTERVENTIONS
      AND RESULTS: In contrast to previous open fetal cleft lip repairs in the same
      model, none of the five fetuses reported here had a good aesthetic result.
      Although there was no evidence of scar histologically, the edges of the lip were
      poorly approximated. The epithelial lining and underlying dermis of the wound
      margins were notably inverted. The orbicularis oris muscle, which had been
      reapproximated, appeared thin and hypoplastic. Most of the vermilion elements
      were poorly aligned, and in one animal, there was a complete dehiscence of the
      repair. CONCLUSIONS: In a more representative model of cleft lip that is not an
      acute lip wound, in utero endoscopic suture repair of the ovine lip gave a poor
      result using current technology. Only a meticulously performed, multilayered,
      open repair of a cleft appears to give a good cosmetic and functional outcome.
      Further studies to improve the endoscopic repair as our technology advances are
      therefore warranted.

PMID- 9761563
TI  - Survey of dentists' experience with cleft palate children in Chile.
AB  - OBJECTIVE: This study was designed to study the experience of dentists with
      children with palatal clefts seeking treatment in Santiago, Chile. DESIGN: A 13
      item questionnaire was sent to 203 pediatric and general dentists treating
      children. Of the 141 dentists who voluntarily completed the questionnaire, 118
      were selected for this study. These professionals worked in private and public
      health centers in the Santiago, Chile, metropolitan area. RESULTS AND
      CONCLUSIONS: The results showed that a majority of dentists had treated a low
      number (1 to 3) of cleft palate children in the previous years, using a
      combination of preventive-curative and radical treatments. Although a majority
      reported that there were no differences in the treatment of the cleft and
      noncleft children, a majority had problems during the course of treatment. The
      results suggest the need for more current information about the care of cleft
      children.

PMID- 9761564
TI  - Spontaneous cleft palate in a newborn gorilla (Gorilla gorilla gorilla).
AB  - OBJECTIVE: We report the first case of cleft palate in a newborn male gorilla
      (Gorilla gorilla gorilla). CASE HISTORY AND RESULTS: The full-term infant was
      born to clinically healthy, wild-caught parents and survived 5 days. Autopsy
      disclosed a unilateral cleft palate, moderate scalp hemorrhage (birth versus
      postnatal trauma), cerebral edema, and a sterile fibrin vegetation in the heart.
      The palate was also shorter and narrower than expected, and the biorbital breadth
      was reduced; otherwise, growth and development appeared normal. Standard cranial
      and intraoral radiographs and three-dimensional reconstructions of computerized
      tomographic (CT) scans provided thorough and noninvasive methods of studying the
      craniofacial complex and extracranial skeleton. By this technique, major findings
      were: intact premaxilla, interpremaxillary, and premaxillary/maxillary sutures;
      intramaxillary cleft with ipsilateral choanal atresia; mildly asymmetric inferior
      turbinates; and normal nasal septum and vomer. CONCLUSIONS: Except for choanal
      atresia, cleft palate was not associated with other major craniofacial or
      extracranial anomalies in this case. Choanal atresia has been observed at times
      with cleft palate, but to our knowledge, the association has not been reported in
      nonhuman primates. Cleft palate, with or without cleft lip, has been recognized
      in a variety of nonhuman primates, including the lemur, marmoset, tamarin,
      squirrel monkey, and macaque. Some occurrences are spontaneous, while others are
      syndromic and/or arise from genetic or teratogenic influences. Each mode of
      presentation is poorly understood in nonhuman primates, but in this case, the
      absence of relevant environmental or parental history suggests that the
      occurrence was spontaneous. Anatomic studies of nonhuman primates are
      particularly valuable when they involve endangered species and will hopefully
      increase our understanding of the pathogenesis and etiology of congenital
      disorders, as well as other relationships between nonhuman primates and humans.

PMID- 9761565
TI  - A comparison of two different bone-harvesting techniques for secondary alveolar
      bone grafting in patients with cleft lip and palate.
AB  - OBJECTIVE: To compare the outcome of the trephine with open hip surgery for
      alveolar bone grafting in cleft lip and palate surgery. DESIGN: The study was
      retrospective. The radiographs were assessed blindly and on two separate
      occasions 1 week apart. SETTING: University Teaching Hospital. PATIENTS,
      PARTICIPANTS: In one group (group A), a trephine was used; in the other (group
      B), open hip surgery was employed. Group A was comprised of 16 patients (nine
      with unilateral and seven with bilateral clefts of the lip and palate) and group
      B, 13 patients (eight unilateral and five bilateral). The prime entry criterion
      for inclusion in the study was that the canine tooth had erupted into the graft
      site. INTERVENTIONS: A long cone periapical radiograph was taken of the erupted
      canine tooth in the graft site. MAIN OUTCOME MEASURE: The radiographs were graded
      from type I to type IV, as described by Bergland et al. (1986a). A comparison was
      also made of the eruption of the canine, postoperative morbidity, and length of
      stay in hospital for each group. RESULTS: There was no statistically significant
      difference in the interdental bone height (p=.61, Mann-Whitney U test). In group
      A, all patients had a satisfactory clinical outcome (type I or II), and in group
      B, only one patient had an unsatisfactory result (type III). The spontaneous
      eruption of the canine and the number of nights spent in the hospital were also
      similar for both groups. However, no patients in group A suffered postoperative
      complications, whereas three patients in group B reported either a limp or
      postoperative infection of the hip. CONCLUSION: Both techniques produced
      satisfactory repair of the bony defect, but the open hip surgery resulted in
      greater postoperative morbidity.

PMID- 9761566
TI  - Salvaging the failed pharyngoplasty: intervention outcome.
AB  - OBJECTIVE: This paper reports on the rates of failure of operations (pharyngeal
      flap and sphincter pharyngoplasty) performed for management of velopharyngeal
      dysfunction, and outcome following their revision. DESIGN: Anatomic abnormalities
      associated with unacceptable vocal resonance and nasal air escape following
      pharyngeal flap and sphincter pharyngoplasty were critiqued. The results of
      primary pharyngeal flap were evaluated for 65 patients, and the results of
      primary sphincter pharyngoplasty were evaluated for 123 patients. All patients
      were treated for velopharyngeal dysfunction. The definition of surgical failure
      was based on persistent hypernasality and/or nasal turbulence on perceptual
      speech evaluation, and incomplete velopharyngeal closure on instrumental
      evaluation, at least 3 months postoperatively. SETTING: All patients were
      evaluated and managed at the Cleft Palate and Craniofacial Deformities Institute,
      St. Louis Children's Hospital, a tertiary cleft care center. PATIENTS,
      PARTICIPANTS: All patients had failed surgical management initially, either with
      pharyngeal flap or sphincter pharyngoplasty, and all underwent repeat
      preoperative and postoperative perceptual speech evaluations; real-time lateral
      phonation fluoroscopy including still reference views; and flexible nasendoscopy
      of the velopharynx using standard speech protocols. INTERVENTIONS: Revisional
      surgery for both procedures consisted of either tightening of the sphincter
      pharyngoplasty or pharyngeal flap port(s) or reinsertion of the sphincter
      pharyngoplasty or pharyngeal flaps following dehiscence. MAIN OUTCOME MEASURES:
      The main outcome measure was normalcy of velopharyngeal function, i.e.,
      elimination of perceptual hypernasality and instrumental evidence of complete
      velopharyngeal closure. The rates of pharyngeal flap failure and sphincter
      pharyngoplasty failure were determined for those patients requiring surgical
      revision. RESULTS: Thirteen of 65 patients (20%) who underwent primary pharyngeal
      flap required revisional surgery. Of these 13 patients, eight were managed
      successfully with a single revisional operation. The remaining five patients
      (38%) continued to exhibit velopharyngeal dysfunction and underwent a second
      revision consisting of tightening or augmentation of the lateral ports. Speech
      results were satisfactory in all patients so treated; however, hyponasality with
      no other airway morbidity occurred in all five. Twenty of 123 patients (16%) who
      underwent primary sphincter pharyngoplasty required surgical revision. Of these
      20 patients, 17 were managed successfully. For both procedures, the principal
      cause of failure was partial or complete flap dehiscence. CONCLUSIONS: Rates of
      primary pharyngeal flap failure are roughly equivalent to rates of primary
      sphincter pharyngoplasty failure. Pharyngeal flap and sphincter pharyngoplasty
      failures can be salvaged with revisional surgery, which can provide a
      velopharyngeal mechanism capable of complete closure. Revisional surgery is
      usually associated with denasal speech.

PMID- 9761568
TI  - Transmission of mutans streptococci between mothers and children with cleft lip
      and/or palate.
AB  - OBJECTIVE: The aim of this study was to investigate the transmission of
      Streptococcus mutans between children with cleft lip and/or palate and their
      mothers. DESIGN: Saliva samples of 21 mother-child pairs were collected and
      cultured on plates containing a selective growth medium for mutans streptocci. At
      least five separate colonies of each colony morphotype were isolated. A
      polymerase chain reaction (PCR) with randomly chosen primers was used to type the
      isolates. RESULTS: The number of morphotypes and PCR types was significantly
      lower in the children than in the mothers. Significant correlations were found
      between the number of morphotypes and PCR types, in the children as well as in
      the mothers. In only 38% of the mother-child pairs were the same PCR types found
      in mother and child. CONCLUSIONS: This suggests that S. mutans had been
      transmitted from mother to child in one-third of the population studied. No
      correlations were found among the number of colony-forming units, the number of
      colony-colony-morphotypes, and the number of PCR types of the mothers and
      transmission. Similar PCR types in mother and child were found significantly more
      often in children who had more than one PCR type. The results indicate that
      transmission of S. mutans from mother to child is not frequent in children with
      oral cleft. This may have consequences for preventive treatment of cleft lip
      and/or palate children and their mothers.

PMID- 9761567
TI  - Branchio-oculo-facial syndrome with cleft lip and bilateral dermal thymus.
AB  - OBJECTIVE: The objective of this study was to demonstrate that the branchiooculo
      facial (BOF) syndrome is a cervicocephalic neural crest maldevelopment. RESULTS:
      Using an embryologic study, we linked the clinical features and the level of the
      neural crest deficiency. We report here two cases of BOF syndrome with a
      particular branchial cleft presenting as bilateral supernumerary thymus glands on
      the surface of the skin; one of the cases was associated with tetralogy of
      Fallot. One patient underwent lip reconstruction at 4 months, combined with
      excision of bilateral auricular pits and superior labial fistula. The other
      patient had a surgical correction of the tetralogy of Fallot, and at 2 months,
      the two stages of the lip reconstruction were performed, combined with bilateral
      auricular pit excision. Both patients have shown normal developmental patterns to
      date. CONCLUSION: The BOF syndrome must be considered as a neurocristopathy at
      different levels, with a tiny mesencephalo-prosencephalic lesion and a severe
      rhombencephalic lesion that includes seven consecutive hindbrain segments, from
      rhombomere 2 to rhombomere 8.

PMID- 9761569
TI  - Dilatation of the infrarenal aneurysm neck after endovascular exclusion of
      abdominal aortic aneurysm.
AB  - PURPOSE: To determine the fate of the infrarenal aneurysm neck and suprarenal
      aorta after endovascular exclusion of abdominal aortic aneurysms (AAAs). METHODS:
      Thirty-four patients underwent endovascular AAA repair between January 1994 and
      December 1995 using custom-made stent-grafts constructed from polyester graft
      material and modified self-expanding Gianturco Z-stents sutured to the graft
      orifices. Thirty-one patients were available for follow-up. Pre- and
      postimplantation diameters were measured using spiral computed tomography in the
      infrarenal aneurysm neck and the suprarenal aorta at the level of the superior
      mesenteric artery (SMA). RESULTS: The mean follow-up time was 25 months. There
      was a significant increase of the diameter of the infrarenal aneurysm neck (+
      1.65 mm, p = 0.002), but not in the aorta at the level of the SMA (+0.52 mm, p =
      0.100). There was no difference in the change in diameter in the infrarenal neck
      in the group with a stent adjacent to the level of measurement (n = 20) compared
      with the group without an adjacent stent (n = 11, p = 0.790). There was no
      correlation between preimplantation size of the infrarenal neck and its diameter
      change (r = 0.14, p = 0.488). There was no correlation (r = 0.10, p = 0.603) or
      association (chi-square test, p = 0.211) between aortic diameter change at the
      level of the SMA and the infrarenal neck. CONCLUSIONS: This investigation shows a
      significant dilatation of the infrarenal aneurysm neck, but not in the suprarenal
      aorta, after endovascular AAA repair with this device. The clinical significance
      of these findings is unclear. Whether such a dilatation in the infrarenal
      aneurysm neck may affect the long-term attachment of stent-grafts remains to be
      shown in the future.

PMID- 9761570
TI  - Changes in referral practice, workload, and operative mortality after
      establishment of an endovascular abdominal aortic aneurysm program.
AB  - PURPOSE: To determine the change in referral practice following establishment of
      an endovascular abdominal aortic aneurysm (AAA) program. METHODS: A prospective
      audit of all elective admissions for AAA was established in January 1994 at the
      initiation of an endovascular AAA program. A comparison was made between this
      cohort and the elective AAA repairs performed between 1981 and 1993. RESULTS:
      Since January 1994, 213 AAA patients (177 men; median age 73 years, range 54 to
      88) have been referred for potential endovascular aneurysm repair. To date, 142
      patients have undergone elective surgery (41 endovascular and 101 conventional).
      Between 1981 and 1993, 304 patients (255 men; median age 69 years, range 45 to
      86) had elective aneurysm repair. Comparison of the two time periods has revealed
      significant increases in the number of tertiary referrals (41.8% versus 9.5%, p <
      0.01), annual operations (50 versus 23, p < 0.05), and overall mortality (12%
      versus 6.7%, p < 0.05), the latter attended by a significant increase in
      cardiorespiratory comorbidity. CONCLUSIONS: The higher elective AAA mortality
      rate since the establishment of an endovascular program reflects a change in
      referral practice and may be directly attributable to an increase in the number
      of high-risk patients. An endovascular AAA program has clinical and financial
      implications for the hospital concerned.

PMID- 9761571
TI  - Experience with the Stentor endograft at four Italian centers.
AB  - PURPOSE: To report the outcome of an Italian multicenter trial of endovascular
      abdominal aortic aneurysm (AAA) exclusion using the Stentor device. METHODS:
      Between April 1995 and July 1996, 66 patients (63 men; average age 69 years,
      range 53 to 84) with infrarenal AAAs meeting the inclusion criteria were
      enrolled. The average diameter of the aneurysm was 4.6 cm (range 4.2 to 7). Three
      (4.5%) of the 66 AAAs were anastomotic aneurysms. RESULTS: Sixteen (25%) tubular
      and 50 (76%) bifurcated endograft procedures were attempted; 4 (6.1%) were
      converted and 1 terminated owing to technical faults with the bifurcated graft's
      second limb. One tube graft was too short and failed to exclude an anastomotic
      aneurysm. Sixty (91%) endograft procedures were completed successfully. Six
      (9.1%) vascular complications occurred, three in one patient who subsequently
      died of pulmonary embolism 72 hours postoperatively (1.5% mortality). There were
      four (6.1%) proximal endoleaks; two sealed spontaneously in < 1 month, and a
      third was converted (7.6% conversion rate). The fourth is being observed.
      Clinical success (aneurysm exclusion with no death or endoleak) at 30 days was
      86.3% (57/66). In the 23-month follow-up of 57 eligible patients, 2 patients died
      of unrelated causes and 1 graft limb thrombosed, requiring a crossover femoral
      bypass. One patient was converted to surgical repair at 5 months postoperatively
      when increasing aneurysm size signaled an undisclosed endoleak (1.8% late
      conversion rate). Five other secondary endoleaks were treated with endovascular
      techniques. CONCLUSIONS: The Stentor was technically feasible in 10% to 40% of
      AAA candidates in this study, although deployment of the second limb was
      problematic in the bifurcated device. Introduction of the second-generation
      Vanguard endograft brought this study to an end.

PMID- 9761573
TI  - Spiral CT angiography versus aortography in the assessment of aortoiliac length
      in patients undergoing endovascular abdominal aortic aneurysm repair.
AB  - PURPOSE: To compare measurements of aortoiliac length obtained with spiral
      computed tomographic angiography (CTA) and aortography in patients undergoing
      endovascular aneurysm repair. METHODS: The distances from the lower-most renal
      artery to the aortic bifurcation and from the aortic bifurcation to the common
      iliac artery (CIA) bifurcation were measured using both CTA and aortography in
      108 patients with abdominal aortic aneurysms. RESULTS: The level of agreement
      between CTA and aortography was high, with 69% of aortic and 76% of iliac
      measurements within 1 cm and > 90% within 2 cm of each other. Mean differences
      were -0.35 +/- 1.20 cm and 0.25 +/- 1.10 cm, respectively, for aortic and iliac
      lengths. Aortography overestimated renal artery to aortic bifurcation length in
      comparison to CTA (p = 0.003), particularly in patients with large aneurysms (>
      6.5 cm) and lumen diameters > 4.5 cm (p < 0.0001). Measurements of CIA length
      were shorter by aortography than CTA (p = 0.02). CONCLUSIONS: There is a high
      level of agreement between CTA and aortography in the measurement of aortoiliac
      length, but aortography overestimates renal artery to aortic bifurcation length
      in patients with large-diameter aneurysms and wide aneurysm lumens. CTA is
      sufficiently accurate in the majority of cases to be used as the sole basis for
      the construction of endovascular grafts.

PMID- 9761572
TI  - Torsion and kinking of unsupported aortic endografts: treatment by endovascular
      intervention.
AB  - PURPOSE: To describe the management strategies used to deal with twisted aortic
      endografts. METHODS AND RESULTS: Two patients with successfully excluded aortic
      aneurysms developed symptoms referable to previously undetected twists in their
      endografts (one EndoVascular Technologies [EVT] and one customized aortomonoiliac
      device). The limb graft occlusion in the EVT graft was treated surgically with a
      femorofemoral bypass, but the aortomonoiliac endograft was salvaged with
      percutaneous implantation of a Wallstent. During another aortomonoiliac
      procedure, suboptimal flow through the endograft was traced to contortion of the
      endograft as it passed over an angulated proximal aneurysm neck. An X-large
      Palmaz stent was deployed to support the graft at this point. CONCLUSIONS:
      Unsupported aortic endografts may develop twists and kinks during deployment that
      can lead to low outflow and graft occlusion. Endovascular techniques are
      available to repair these defects postoperatively, although more precise
      intraoperative assessment tools may identify these problems so that they can be
      corrected at the initial intervention.

PMID- 9761574
TI  - Percutaneous endoluminal treatment of iliac occlusions: long-term follow-up in
      105 patients.
AB  - PURPOSE: To evaluate the long-term results of percutaneous recanalization
      techniques in occluded iliac arteries. METHODS: Percutaneous recanalization was
      attempted in 105 patients (97 men; mean age 56 years, range 34 to 80) with iliac
      occlusions using thrombolysis (n = 15), excimer laser (n = 4), mechanical
      thrombectomy (n = 16), balloon angioplasty alone (n = 23), and angioplasty plus
      stenting (n = 69). The majority of lesions (n = 72) were in the common iliac
      artery (CIA); 33 were in the external iliac artery (EIA). RESULTS: The primary
      recanalization rate was 88% (92/105) independent of location (EIA: 90%, CIA: 86%)
      and lesion length, but dependent on age of thrombus (< 3 months: 100%, > 3
      months: 79%, p < 0.02). Complications included 5 (4.8%) cases of distal embolism
      treated by thromboaspiration or Fogarty balloon embolectomy. Seven (6.7%) early
      thromboses were treated surgically. Primary and secondary patency rates were
      calculated at 6 years for all 105 cases and for the 92 recanalized lesions using
      life-table analysis. Overall, primary patency was 52% (CIA: 58%, EIA: 34%) and
      secondary 66% (CIA: 74%, EIA: 40%). Lesions < 6 cm had a primary patency of 70%,
      while those > 6 cm had a 31% rate (p < 0.01). Secondary patencies were 86% and
      42%, respectively (p < 0.01). Among recanalized lesions, the primary patency was
      61% (CIA: 69%, EIA: 38%) and secondary 77% (CIA: 88%, EIA: 45%; p < 0.05).
      Lesions < 6 cm had a primary patency rate of 72%, while longer lesions had a
      primary rate of 44% (p < 0.04); secondary patencies were 89% and 59%,
      respectively (NS). Primary patency without stent was 57% and with stent 65% (NS);
      secondary patency without stent was 71% and with stent 82% (NS). CONCLUSIONS:
      Percutaneous recanalization of iliac occlusions represents a true alternative to
      vascular surgery and a first-line treatment option. Stents have a tendency to
      improve long-term results and are recommended for routine use in chronic iliac
      occlusions.

PMID- 9761575
TI  - Outpatient endovascular intervention: is it safe?
AB  - PURPOSE: To evaluate the feasibility and safety of outpatient percutaneous
      endovascular intervention in the treatment of arterial occlusive disease.
      METHODS: The records of 134 patients who underwent 151 outpatient endovascular
      procedures between 1992 and 1997 were reviewed retrospectively. According to
      established protocol, focal lower limb (n = 145) and subclavian (n = 6) arterial
      lesions requiring relatively straightforward endoluminal interventions were
      appropriate for outpatient management provided the patients were free of
      significant comorbidities. A percutaneous transfemoral approach was used for
      lower limb lesions, while subclavian angioplasty was performed via a brachial
      access. Heparin anticoagulation was administered conservatively. Patients were
      discharged 3 hours after sheath removal. RESULTS: The majority (98%) of patients
      were discharged as planned. Three (2%) patients were observed overnight in the
      hospital for treatment of acute iliac artery thrombosis, puncture-site bleeding,
      and suboptimal angioplasty. No patient required hospitalization following
      discharge. Periprocedural morbidity was confined to 2 (1.5%) groin hematomas and
      1 (0.7%) femoral pseudoaneurysm. CONCLUSIONS: Outpatient endovascular
      intervention appears safe; however, proper case selection and technical
      excellence are inseparable components for the success of this strategy.

PMID- 9761577
TI  - Carotid plaque characterization: helpful to endarterectomy and endovascular
      surgeons.

PMID- 9761576
TI  - Carotid plaque characterization using digital image processing and its potential
      in future studies of carotid endarterectomy and angioplasty.
AB  - PURPOSE: To corroborate the validity of a computerized methodology for evaluating
      carotid lesions at risk for stroke based on plaque echogenicity. METHODS: The
      records of 96 carotid endarterectomy patients (59 men; median age 69.5 years,
      range 52 to 83) with stenoses > 50% were studied retrospectively. Forty-one
      patients (43%) had been symptomatic preoperatively. All patients had undergone
      computed tomography (CT) to detect infarction in the carotid territory and a
      duplex scan to measure carotid stenosis. Plaque echogenicity was analyzed by
      computer, expressing the echodensity in terms of the gray scale median (GSM). The
      incidence of CT-documented cerebral infarction was analyzed in relation to
      symptomatology, percent stenosis, and echodensity. RESULTS: Symptoms correlated
      well with CT evidence of brain infarction: 32% of symptomatic patients had a
      positive CT scan versus 16% for asymptomatic plaques (p = 0.076). The mean GSM
      value was 56 +/- 14 for plaques associated with negative CT scans and 38 +/- 13
      for plaques from patients with positive scans (p < 0.0001). However, there was no
      difference in the GSM value between plaques with > or < 70% stenosis.
      Furthermore, the incidence of CT infarction was 40% in the cerebral territory of
      carotid plaques with a GSM value < 50 and only 9% in those with a GSM > 50 (p <
      0.001). CONCLUSIONS: Computerized analysis of plaque echogenicity appears to
      provide clinically useful data that correlates with the incidence of cerebral
      infarction and symptoms. This method of analyzing plaque echolucency could be
      used as a screening tool for carotid stent studies to identify high-risk lesions
      better suited to conventional surgical treatment.

PMID- 9761578
TI  - Assessment of apparent vena caval penetration by the Greenfield filter.
AB  - PURPOSE: To examine and elucidate the mechanisms for apparent "penetration" by
      Greenfield vena caval filters. METHODS: Two filters were placed in the inferior
      venae cavae (IVC) of four immature sheep and followed with cavography for 1 year.
      Two animals underwent computed tomography (CT) and laparoscopic examination. At
      necropsy, the vena cava and adjacent structures of all four animals were examined
      grossly and histologically. RESULTS: Based upon cavography and CT imaging, all
      filters appeared to penetrate the vena cava at 12 months. However, at
      laparoscopy, no hooks or limbs were exposed, and the pericaval tissues remained
      intact; each hook or limb was within the adventitia or encapsulated in scar
      tissue. Histology of the tissue at the hook sites revealed remodeling of the
      intimal surface of the IVC and thinning of the adventitia. CONCLUSIONS: Based
      upon these data, we hypothesize that the vena cava gradually adapts by medial and
      adventitial thinning and myointimal remodeling to the radial force exerted by a
      filter. This process allows increase in the filter base diameter while
      maintaining the integrity of the cava and protecting adjacent structures.

PMID- 9761579
TI  - Femoral artery exposure for endovascular aneurysm repair through oblique
      incisions.
AB  - PURPOSE: To offer an alternative technique for accessing the femoral artery prior
      to endovascular grafting. TECHNIQUE: An oblique incision is made over the medial
      half of the inguinal ligament and continues to the femoral sheath, which is
      opened longitudinally. The distal external iliac artery and proximal common
      femoral artery are isolated. A tiny stab wound is made distal to the primary
      wound for femoral artery puncture and catheter access. CONCLUSIONS: Using an
      oblique incision at the level of the inguinal ligament optimizes exposure for
      endograft insertion and may minimize the frequency of serious wound
      complications.

PMID- 9761580
TI  - A method for adjusting a malpositioned bifurcated aortic endograft.
AB  - PURPOSE: To report the successful application of a method to adjust a
      malpositioned bifurcated stent-graft after endovascular aortic aneurysm repair.
      METHOD AND RESULTS: A 62-year-old male patient underwent endovascular repair of a
      5.1-cm abdominal aortic aneurysm (AAA) with a Vanguard bifurcated stent-graft.
      After complete deployment of the stent-graft, the intraoperative completion
      angiogram disclosed unexpected occlusion of the left renal artery. Intra-aortic
      adjustment of the bifurcated graft was possible with a crossover guidewire, which
      was pulled caudally. The method worked perfectly to restore blood flow to the
      left renal artery. The patient is well 16 months postoperatively without any
      evidence of endoleak or graft migration; the left renal artery remains open.
      CONCLUSIONS: A technique is demonstrated for intra-aortic repositioning of a
      bifurcated stentgraft to correct insufficient deployment. If required, this
      technique should be attempted before conversion to an open procedure.

PMID- 9761581
TI  - Troubleshooting maldeployed aortic endografts.

PMID- 9761582
TI  - Aortoenteric fistula caused by a ruptured stent-graft: a case report.
AB  - PURPOSE: To report a case of aortoenteric fistula secondary to endovascular
      abdominal aortic aneurysm (AAA) exclusion using the Stentor bifurcated
      endovascular graft. METHODS AND RESULTS: Seventeen months after a successful
      endovascular AAA procedure, a male patient developed upper gastrointestinal
      bleeding. An aortoenteric fistula was diagnosed. At operation, the endograft
      fabric was found to be ruptured in an area of suture disruption between the
      nitinol stents. Coincidentally, a pre-existing inflammatory process might have
      caused adhesions between the bowel and the aortic wall, predisposing to fistula
      formation. The patient recovered after placement of a conventional aortic graft.
      CONCLUSIONS: Suture disruption between the internal support stents is a
      recognized complication in the first-generation Stentor device. Although the case
      described here is probably not typical of the consequences of this sequela, it
      does reinforce the need for continual periodic imaging to check for signs of
      graft disruption in Stentor endografts.

PMID- 9761583
TI  - Late failure of early-model endografts: a complication whose time has come?

PMID- 9761584
TI  - Late aortic arch perforation by graft-anchoring stent: complication of
      endovascular thoracic aneurysm exclusion.
AB  - PURPOSE: To describe a fatal case of late aortic perforation by an endograft
      anchoring stent. METHODS AND RESULTS: A 69-year-old woman presented 2 years after
      thoracoabdominal aneurysm repair with a 9-cm dilatation of the descending
      thoracic aorta proximal to the conventional aortic graft. A 38-mm Dacron graft
      with multiple Gianturco Z-stents sutured inside was placed transluminally across
      the aortic arch such that part of the uncovered portion of the proximal stent was
      partially across the left subclavian orifice. Four months later, the patient died
      from massive hemorrhage. Autopsy showed that the uncovered portion of the
      proximal stent had perforated the aortic arch. CONCLUSIONS: This case stresses
      the need for low-profile stent-grafts and smaller, more flexible introducer
      systems. Anchoring stents must be flexible, less traumatic, and strong enough to
      create a watertight seal even in tortuous vessels. To avoid aortic arch damage by
      thoracic stent-grafts, the proximal stent should be fully covered by the fabric.

PMID- 9761585
TI  - Endovascular repair of aortic aneurysms in the the presence of a horseshoe
      kidney.
AB  - PURPOSE: To report two cases of endovascular aortic aneurysm exclusion in
      patients with a horseshoe kidney. METHODS AND RESULTS: Two male patients, one
      with a known horseshoe kidney and history of multiple previous laparotomies,
      presented with abdominal aortic aneurysms of approximately 6-cm diameter. Each
      was treated with a tapered aortomonoiliac polytetrafluoroethylene graft secured
      proximally with a Palmaz balloon-expandable stent. The endograft was sutured
      distally to a Dacron femorofemoral crossover graft. An anomalous renal vessel was
      sacrificed in one case. The aneurysms were successfully excluded, and the
      patients recovered without sequelae. CONCLUSIONS: Endovascular repair should be
      considered as a treatment option in patients with aortic aneurysm in the presence
      of a horseshoe kidney, particularly if the renal vasculature can be wholly
      preserved.

PMID- 9761586
TI  - Hypercoagulability and the management of anticoagulant therapy in surgical
      patients: review and recommendations.

PMID- 9761587
TI  - Symposium overview: the use of delayed matching-to-sample procedures in studies
      of short-term memory in animals and humans.
AB  - Behavioral paradigms applicable for use in both human and nonhuman subjects for
      investigating aspects of working/short-term memory are presented with a view
      towards exploring their strengths, weaknesses, and utility in a variety of
      experimental situations. Such procedures can be useful in teasing out specific
      aspects of mnemonic processes including discrimination, encoding, and retention.
      Delayed matching-to-position, delayed matching-to-sample (DMTS), and titrating
      matching-to-sample procedures are highlighted. Additionally, the application of
      DMTS tasks in preclinical and clinical settings is presented: drug effects on
      memory processes can be explored preclinically in animal models; normative data
      have been developed in human populations where they have been used in adults to
      explore the relationships between mnemonic processes and specific clinical
      entities such as Parkinsonism, senile dementia of the Alzheimer's type,
      schizophrenia, and depression. Studies in children indicate that encoding and
      retention processes improve rapidly in the early years, plateauing prior to
      puberty. Noninvasive imaging techniques such as positron emission tomography
      (PET) indicate that activity in specific brain areas is associated with DMTS task
      performance and may serve to confirm roles for such structures in mnemonic
      processes.

PMID- 9761588
TI  - Comparison of the behavior of the curly tail and CBA mouse on a neurologic scale.
AB  - ct/ct mice are a mutation of the CBA strain with a high incidence of spina bifida
      (SB). Because humans with SB can exhibit abnormal behavior, we compared ct/ct and
      CBA mice using a neurologic assessment tool. ct/ct mice are more active and
      engage in more climbing, and stereotypical and compulsive behavior. When
      stimulated during cage removal ct/ct mice react more vigorously. ct/ct mice react
      more vigorously to a novel stimulus, and will vigorously search for a stable
      surface during visual placement. In the open field ct/ct mice crossed more lines
      and reared more than CBA. ct/ct mice demonstrated deficient performance in a
      modified Morris water maze. No differences were noted for other behaviors tested.
      The results argue that the mutation that produces SB in ct/ct mice also alters
      brain structure or chemistry. This is consistent with the findings in humans
      where SB can produce a variety of behavioral anomalies, most notably
      hyperactivity, attentional disorders, learning disabilities, and developmental
      lags.

PMID- 9761589
TI  - Cognitive and sensorimotor functions in 6-year-old children in relation to lead
      and mercury levels: adjustment for intelligence and contrast sensitivity in
      computerized testing.
AB  - Within a larger environmental health screening program neurobehavioral measures
      were taken in 384 6-year-old children (mean age 74 months) in the cities of
      Leipzig, Gardelegen, and Duisburg. Lead concentrations in venous blood samples
      (PbB) and urinary mercury excretion in 24-h samples (HgU) were measured as
      markers of environmental exposure by electrothermal AAS. Dependent variables
      included two subtests from the WISC [vocabulary (V) and block design (BD)] as
      well as five tests from the NES2 [pattern comparison, pattern memory, tapping,
      simple reaction time, and the continuous performance test (CPT; child version)].
      In addition, visual functions [visual acuity (TITMUS-test) and contrast
      sensitivity (FACT)] were tested as covariates. The overall average PbB (geometric
      mean) was 42.5 microg/l (upper 95% value = 89 microg/l). The overall average
      mercury excretion (HgU) was 0.16 microg/24 h. Whereas no significant or
      borderline associations between HgU and any of the target variables was found,
      significant negative associations were observed between PbB and verbal
      intelligence (WISC vocabulary but not WISC Block Design) and false-positive
      responses (false alarms), as well as false-negative responses (miss) in the CPT.
      Whereas parental education was the most important confounder for WISC
      performance, visual contrast sensitivity and computer familiarity also proved
      predictive for performance in several computer-based NES subtests. It is
      concluded that non-IQ measures, namely measures of sustained attention, are
      negatively affected in children with 95% of blood-lead levels below 90 microg/l,
      even after adjustment for intelligence and contrast sensitivity, whereas the
      causative role of lead in altering IQ functions remains somewhat equivocal,
      because important covariates could not be controlled for.

PMID- 9761590
TI  - Ethanol inhibition of brain ornithine decarboxylase activity in the postnatal
      rat.
AB  - The purpose of this study was to determine the relationship between ornithine
      decarboxylase activity (ODC; a marker for perturbed cell development), the blood
      alcohol level, and alcohol-induced microencephaly in the developing rat brain
      after binge treatment with ethanol vapour. By manipulating ethanol flow we were
      able to adjust vapour concentrations (24-65 mg ethanol/l air) such that an acute
      exposure of ethanol vapour for 3 h resulted in a range of blood alcohol levels
      (2.3-5.5 mg/ml). Acute studies showed that ethanol dose-dependently inhibited rat
      hippocampal and cerebellar ODC activity at PND4-PND10. There was a significant
      correlation between the blood alcohol level and degree of inhibition at all ages
      tested. Chronic treatment from PND4 to PND9 caused a significant decrease in both
      brain to body weight ratio and in hippocampal and cerebellar ODC activities at
      PND10. These results indicate that ethanol-induced disruption in ODC could play a
      significant role in ethanol's teratogenic effects during early postnatal
      development.

PMID- 9761591
TI  - Enhancement of cocaine-induced hyperthermia fails to elicit neurotoxicity.
AB  - The neurotoxic potential of cocaine when administered under conditions conducive
      to the initiation of hyperthermia was investigated. Rats were administered
      cocaine at ambient temperatures of 22 degrees C or 30 degrees C. To determine the
      thermal response, body temperatures were measured every 30 min and the total
      thermal response (TTR), representing the area under the temperature vs. time
      curve, was calculated. Saline administered at 22 degrees C or 30 degrees C
      resulted in a normal thermal response (TTR = 9.8+/-0.9 and 11.2+/-0.9,
      respectively). Cocaine administration resulted in ambient temperature-dependent
      hyperthermia. Cocaine (4 x 25 mg/kg) administered at 22 degrees C resulted in a
      TTR of 15.1+/-0.9 whereas cocaine (4 x 15 or 25 mg/kg) administered at 30 degrees
      C resulted in TTRs of 22.2+/-0.9 and 21.9+/-0.8, respectively. Regardless of the
      dose or thermal response, cocaine administration did not result in depletion of
      dopamine (DA) or serotonin (5-HT) in the caudate-putamen. Cocaine administration
      also failed to induce an increase in the concentration of glial fibrillary acidic
      protein (GFAP), a marker for neurotoxicity. These results demonstrate that
      hyperthermia does not promote cocaine-induced neurotoxicity in the rat caudate
      putamen.

PMID- 9761592
TI  - Influence of chronic fluorosis on membrane lipids in rat brain.
AB  - Brain membrane lipid in rats were analyzed after being fed either 30 or 100 ppm
      fluoride for 3, 5, and 7 months. The protein content of brain with fluorosis
      decreased, whereas the DNA content remained stable during the entire period of
      investigation. After 7 months of fluoride treatment, the total brain phospholipid
      content decreased by 10% and 20% in the 30 and 100 ppm fluoride groups,
      respectively. The main species of phospholipid influenced by fluorosis were
      phosphatidylethanolamine, phosphatidylcholine, and phosphatidylserine. The fatty
      acid and aldehyde compositions of individual phospholipid classes were unchanged.
      No modifications could be detected in the amounts of cholesterol and dolichol.
      After 3 months of fluoride treatment, ubiquinone contents in brain were lower;
      however, at 7 months they were obviously increased in both groups of fluoride
      treatment. The results demonstrate that the contents of phospholipid and
      ubiquinone are modified in brains affected by chronic fluorosis and these changes
      of membrane lipids could be involved in the pathogenesis of this disease.

PMID- 9761593
TI  - Prenatal sulfur dioxide exposure induces changes in the behavior of adult male
      mice during agonistic encounters.
AB  - Sulfur dioxide (SO2) is one of the most important pollutants of the western
      countries, responsible for several cardiopulmonary diseases in humans. SO2
      affects both young and adult people, causing low work productivity with social
      and economical costs extremely high for the communities. To test whether or not
      SO2 produces changes in social and/or agonistic behavior of laboratory animals,
      outbred CD-1 male mice were prenatally exposed to different SO2 concentrations
      (0, 5, 12, or 30 ppm) up to pregnancy day 14. At adulthood, following a 4-week
      isolation period, they underwent an aggressive encounter with CD-1 male opponents
      of the same age, body weight, and isolation condition (single 20-min session).
      The levels of several responses such as tail rattling, freezing, and defensive
      postures were reduced by the treatment, particularly during the initial period of
      the agonistic encounter, whereas offensive and attack behaviors were not
      significantly modified. In addition, rearing and social investigation increased.
      Overall, the present results indicate that prenatal SO2 exposure can alter mouse
      social/agonistic behavior, apparently acting on the approach phase toward the
      opponent and suggestive of changes in the animals' capability to cope with
      threatening dangerous situations.

PMID- 9761594
TI  - Perinatal delta9-tetrahydrocannabinol exposure did not alter dopamine transporter
      and tyrosine hydroxylase mRNA levels in midbrain dopaminergic neurons of adult
      male and female rats.
AB  - We have recently demonstrated that the magnitude of L-3,4-dihydroxyphenylacetic
      acid (DOPAC) lowering effect caused by amphetamine in midbrain dopaminergic
      neurons of adult rats was lesser in animals that had been perinatally exposed to
      delta9-tetrahydrocannabinol (delta9-THC) than controls. In the present study, we
      have examined whether this loss in the responsiveness to amphetamine might be due
      to changes at the level of dopamine transporter (DAT), the main molecular site
      for the action of amphetamine, following the perinatal exposure to delta9-THC. To
      this end, we have analyzed DAT mRNA levels, by using in situ hybridization, in
      the substantia nigra and ventral tegmental area, the areas where cell bodies of
      DAT-containing midbrain neurons are located, of adult male and female rats that
      had been perinatally exposed to delta9-THC. In addition, we also analyzed mRNA
      levels of tyrosine hydroxylase (TH), the rate-limiting enzyme in DA synthesis.
      Results were as follows. Both adult male and female rats that had been
      perinatally exposed to delta9-THC exhibited similar mRNA levels to controls for
      both DAT and TH in the substantia nigra as well as in the ventral tegmental area.
      This observation makes it difficult to support the idea that the differences
      found in adulthood after pharmacological challenges were caused by irreversible
      changes at the level of gene expression for these two key proteins.

PMID- 9761595
TI  - Long-term effects of early cocaine exposure on the light responsiveness of the
      adult circadian timing system.
AB  - Early cocaine exposure is associated with a wide variety of neurobehavioral and
      teratogenic effects. The current study was conducted to determine the long-term
      effects of such exposure on the hamster circadian timing system. The circadian
      system drives rhythms in a tremendous diversity of physiological, behavioral, and
      endocrine functions. The fetal circadian pacemaker has recently been shown to
      express a functional D1 dopamine system that is involved in maternal-fetal
      entrainment. Maternally administered cocaine, acting on the fetal clock, could
      therefore potentially have long-lasting effects on exposed offspring. Pregnant
      SCN-lesioned hamsters or their pups, maintained in constant dim illumination
      (DD), were administered cocaine (30 mg/kg, SC, N = 10 litters) or saline vehicle
      (N = 5 litters) from embryonic (E) day 15 [day of mating = E0] through postnatal
      (P) day 5. Upon weaning (P21), cocaine- and saline-treated offspring were placed
      in individual running wheels for a period of 5-6 weeks. Individuals were then
      challenged with 1-h light pulses at three circadian times (CT7, CT14, CT18).
      Cocaine-treated litters had a statistically significant mean phase advance of
      +0.32 h at CT14 compared with the mean phase delay of 2.13 h of the saline
      treated litters. No significant differences were seen at the other two circadian
      times, although there was heterogeneity in the responses among cocaine-treated
      animals. This represents the first demonstration of an effect of perinatal
      cocaine on the circadian timing system. Together with the recent demonstration of
      D1 receptors in the human SCN, these findings raise the possibility that
      gestational cocaine abuse by humans may also lead to later disturbances in the
      circadian timing system.

PMID- 9761596
TI  - Alcohol-induced inhibition of cocaine metabolism and the formation of
      cocaethylene in neonatal rats.
AB  - Due to the significant species differences in the timing of different stages of
      brain development, to study the effects of drugs during the period equivalent to
      the third trimester in humans it is necessary to administer the drugs to neonatal
      rats. rather than in utero. In this study, we investigated the pharmacokinetic
      interactions between alcohol and cocaine. Such information is critical in
      understanding the roles of alcohol and cocaine in mediating neuroteratogenesis.
      Sprague-Dawley rat pups (10 days old) were given IP injections of alcohol (3.3 or
      5.0 g/kg) and/or cocaine (40 mg/kg). At 20, 60, or 100 min (60 and 100 min for
      3.3 g/kg alcohol only) after injections, 20 microl of tail blood was collected
      for blood alcohol concentration (BAC) determination. Immediately after tail blood
      collection, blood was collected and pooled for determinations of blood cocaine
      (BCC), benzoylecgonine (BBC), and cocaethylene concentration (BCEC). The slopes
      of the ascending BAC curves were unaffected in the presence of cocaine. BCC
      levels declined significantly as a function of time after the peak level at 20
      min postinjection time. BCC levels were unchanged in pups receiving 3.3 g/kg
      alcohol, but the levels were significantly higher in 5.0 g/kg pups 20 min after
      injections. BBC concentrations were reduced to nearly 50% in the presence of
      alcohol (both doses) 20 min after injections. BCEC was detected at all time
      points when both alcohol and cocaine were injected. Taken together, these
      findings indicated that the enzymatic systems involved in converting cocaine to
      cocaethylene were functional at an early postnatal age, and the metabolism of
      cocaine was affected by the presence of alcohol in neonatal rats.

PMID- 9761598
TI  - Editorial 

PMID- 9761597
TI  - Proglumide, a cholecystokinin receptor antagonist, exacerbates beta, beta'
      iminodipropionitrile-induced dyskinetic syndrome in rats.
AB  - The present investigation was undertaken to study the effect of proglumide, a
      cholecystokinin (CCK) receptor antagonist, on iminodipropionitrile (IDPN)-induced
      excitation, chorea, and circling (ECC) syndrome in rats. The animals were exposed
      to IDPN in the dose of 100 mg/kg/day IP for 9 days. Proglumide (PG) was
      administered IP daily 1 h before IDPN in the doses of 250, 500, and 750 mg/kg
      body weight in three different groups of rats. The animals were observed daily
      for neurobehavioral abnormalities including dyskinetic head movements, circling,
      tail hanging, air righting reflex, locomotor activity, and contact inhibition of
      the righting reflex. After behavioral studies, blood and brain samples were
      collected for the analysis of malondialdehyde (MDA), conjugated dienes, vitamin
      E, and glutathione peroxidase (GSH-Px). The temporal bones were also collected
      for inner ear histopathology. Our results showed that proglumide significantly
      and dose-dependently exacerbated the incidence and the severity of IDPN-induced
      ECC syndrome during the treatment period as well as up to 3 weeks of postdosing.
      Administration of IDPN produced a significant increase in MDA and conjugated
      dienes and a decrease in vitamin E and GSH-Px, suggesting the role of oxygen
      derived free radicals (ODFR) in IDPN-induced neurotoxicity. Concomitant treatment
      with proglumide potentiated IDPN-induced oxidative stress. The histopathology of
      the inner ear showed significantly high degeneration of sensory hair cells in the
      crista ampullaris of the rats treated with IDPN plus proglumide compared to IDPN
      alone-treated animals. Further studies are warranted to determine the role of CCK
      in nitrile toxicity and drug-induced dyskinesia.

PMID- 9761599
TI  - [Isolation of Vibrio cholerae O1 from aquatic environments and foods in
      Pernambuco State, Brazil].
AB  - Incidence of Vibrio cholerae O1 was studied in 2,585 samples from different
      aquatic environments and 91 from foods in Pernambuco State, northeastern Brazil,
      from 1992 to 1994. A total of 193 (7.21%) samples of V. cholerae were isolated
      with a higher prevalence of the Inaba serovar (183-94.8%) than the Ogawa serotype
      (10-5.1%). All isolates were classified as biotype El Tor, and resistance
      patterns to antibiotics showed that all strains were susceptible tetracycline.
      Some 70 random samples of Vibrio cholerae proved toxigenic, including all the
      Ogawa serovars. Incidence of V. cholerae O1 in river water and sewage (86.0%)
      pointed to fecal contamination as the most common source and vehicle for rapid
      spread of the microorganism in the aquatic environment. The vibrio was isolated
      in 2.1% of all food examined, which was less than expected.

PMID- 9761600
TI  - [Air pollution and living conditions: a geographical analysis of health risk in
      Volta Redonda, Rio de Janeiro, Brazil].
AB  - Air pollution is a widely recognized hazard to human health. In industrial cities
      the emission of toxic gases and particulate matter into the atmosphere compounds
      the pollution problem caused by circulation of vehicles, often creating hazardous
      public health situations. The goal of this study was to analyze patterns in
      pollution and living conditions in Volta Redonda and identify more vulnerable
      areas and population groups. Volta Redonda is a city near Rio de Janeiro with
      250,000 inhabitants and Brazil's main steel industrial complex. The presence of
      several factories in the city, especially the huge CSN steel plant, contributes
      to increased air pollution levels, to the point that this city is one of the most
      heavily polluted in the country. The methodology applied to identify areas and
      groups of people most vulnerable to this sort of pollution utilized a GIS
      software. The study showed that the northwestern area of Volta Redonda had the
      worst environmental and living conditions.

PMID- 9761601
TI  - [Prenatal care in Pelotas, Rio Grande do Sul, Brazil, 1993].
AB  - All 5304 births in the hospitals of Pelotas, Rio Grande do Sul, Brazil in 1993
      were studied. Neonates were examined and their mothers were interviewed regarding
      sociodemographic conditions, family income, reproductive health, and medical care
      during pregnancy. Ninety-five per cent of women received prenatal care. The mean
      number of physician visits during pregnancy was 7 and the majority of the women
      (84.7%) began visits before the fifth month of pregnancy. Women who did not
      receive prenatal care were from the lowest socioeconomic stratum and were mostly
      adolescents or over 40 years of age. Incidence of low birth weight in this group
      was 2.5 times that of the group with more than five visits (p>0.001). Perinatal
      mortality rate was 50.6/1000 in the group without prenatal care and 15.8/1000 in
      the group with more than five visits. With regard to utilization of health care,
      the study shows that twenty-five per cent of women with high gestational risk
      received inadequate prenatal care. The rate was less than 10% in the group of
      women with low gestational risk. These results suggest the need for improvement
      in the quality of prenatal care with special attention for mothers with high
      gestational risk.

PMID- 9761602
TI  - [Effects of survival bias on the prevalence of malnutrition in six-year-old
      children in Brazil, based on the national survey on health and nutrition, 1989].
AB  - Child growth as measured by anthropometric indicators is an important tool for
      assessing children's nutritional status and society's developmental stage. This
      study uses the height-for-age indicator with the cutoff point at -2 Z to estimate
      prevalence of malnutrition in a population of six-year-old children included in
      the Brazilian National Survey on Health and Nutrition (PNSN). Prevalence
      variability was analyzed according to gender, trimestral age range, per capita
      family income, and region of residence. Based on estimates of mortality rates for
      children under five whose deaths could be ascribed to malnutrition, the survival
      bias correction was performed using the Boerma methodology. This correction, in
      turn, was more conspicuous within the low-income and less-developed segment of
      the population. There was an increase in the number of malnourished children in
      relation to those surviving at the time of investigation. When comparing less and
      more developed areas of the country (the Northeast and Southeast, respectively),
      we observed that malnutrition prevalence rates within the six-year-old group
      showed no change in the Southeast region, while in the Northeast they increased
      from 26% to 34%, thus representing a 31% increase in the malnutrition rate.
      Therefore, in absolute figures, these rates account for the addition of 90,100
      children to the malnourished group.

PMID- 9761603
TI  - [Overpricing and affordability of drugs: the case of essential drugs in Mexico].
AB  - Accessibility and availability of drugs has been a matter of great concern for
      health services all over the world, especially for less developed countries. The
      World Health Organization has devoted considerable time to this matter, as
      evidenced in several documents and policies, such as model lists of essential
      drugs and the strategy "Health for All by the Year 2000". The WHO policy for
      essential drugs has been widely accepted, and the WHO List of Essential Drugs is
      now in the ninth revised edition. Although the essential drug policy has been
      well-accepted by health agencies and NGOs, the pharmaceutical industry has not
      proven willing to produce essential drugs at affordable prices. The purpose of
      this study is to examine price levels of essential drugs in Mexico. The
      evaluation was performed through a comparison of international and national
      prices for leading drugs in the respective therapeutic categories and included in
      the WHO model list of essential drugs. The study shows clearly that prices of
      essential brand-name drugs in Mexico are very high. Per capita consumption has
      remained stable despite a sharp decrease in the Mexican GDP since 1995. The
      article discusses the reasons for this and proposes measures to deal with the
      problem.

PMID- 9761604
TI  - [Intestinal parasitism in a Parakana indigenous community in southwestern Para
      State, Brazil].
AB  - To determine the occurrence and epidemiological aspects of intestinal parasites
      among the Parakana indigenous people in the Paranatinga settlement (in the
      eastern Amazon Region), parasitological tests were performed in April 1992 and
      February 1995. One fresh stool specimen was obtained and immediately processed
      using the Hoffman and direct methods. Some 126 samples were obtained in April
      1992 (from a total population of 215 individuals). Some 80. 2% (101) of those
      tested were infected with at least one species of intestinal parasite. Hookworms
      were found in 33.3%, Ascaris lumbricoides 42.8%, Trichuris trichiura 0.8%, and
      Strongyloides stercoralis 5.6%. Entamoeba histolytica and Giardia lamblia
      protozoans were found in 65.0% and 46.8% of those tested, respectively. A second
      parasitological survey was performed on 174 individuals (from a population of
      253) in February 1995. 88.5% were infected. Note that prevalence in February 1995
      was higher than in April 1992 (p=0.04). It was lower for hookworms, E.
      histolytica, and G. lamblia, with no S. stercoralis (p<0.05). Despite provision
      of health care in the Paranatinga community, prevalence of intestinal parasites
      is still extremely high, suggesting that primary and secondary health care should
      be increased immediately to increase the efficacy of prevention of intestinal
      parasites.

PMID- 9761605
TI  - [The national health system and health policies in the Brazilian dentistry
      literature, 1986-1993].
AB  - The Brazilian scientific literature on social and preventive dentistry from 1986
      to 1993 was identified and analyzed to verify whether themes of papers referred
      to health policy and the national health system. Published scientific articles
      were used as the unit of analysis for the study. An analytical survey was
      conducted considering the following variables, amongst others: author's
      institutional affiliation; author's title; author's areas of interest; type of
      research; type of article; and research funding sources. Articles reviewed were
      published between the First and Second National Oral Health Conferences. There
      were 386 articles published in 19 journals, by at least 866 authors. More than
      75% of the studies came from public universities. RGO was the largest publisher
      in this field, followed by Revista da APCD. Original articles accounted for 56.7%
      of the studies, while 30.3% were reviews and essays. The majority of the authors
      were from the State of Sao Paulo. Male writers predominated. A 'quantitative
      deficiency' was identified, since scientific production remained below 50% of its
      potential. Health policy was considered a specific issue in only 3 articles
      (0.8%) while 7 (1.8%) discussed the national health system.

PMID- 9761606
TI  - Caffeine intake and pregnancy outcomes: a meta-analytic review.
AB  - Epidemiological publications on the relationship of caffeine to birth weight and
      duration of human pregnancy, from 1966 to 1995, were searched through Medline.
      Each study was treated as the stratification variable, and its weight average was
      proportional to the inverse of its variance. Twenty-six studies were located.
      Among the twenty-two studies on birth weight, eleven were on mean birth weight,
      nine on low birth weight (LBW), and four on intrauterine growth retardation
      (IUGR). Combined analysis of mean birth weight study results showed a significant
      decrease in birth weight of nearly 43g among newborns of the heaviest caffeine
      consuming mothers. LBW, IUGR, and preterm delivery displayed significant
      homogeneity in the test results, indicating that a pooled estimate should not be
      taken as na adequate measure. The high heterogeneity of the available literature
      on the effects of caffeine on LBW, IUGR, and preterm delivery prevents estimation
      of reliable pooled estimates through meta-analysis. Further assessment of
      caffeine intake during pregnancy is needed in future research.

PMID- 9761608
TI  - [Policy and collective health: a reflection on scientific production (1976
      1992)].
AB  - This study systematizes the theoretical and conceptual foundations in the field
      of Collective Health that have provided the basis for scientific production in
      the health policy area. The primary research source is the literature produced in
      two different contexts in this field, i.e., that of its emergence per se and the
      scope of the so-called Health Reform. The authors highlight the main concepts and
      theoretical references from the social sciences used in analyzing the health
      policy theme, identifying analytical distinctions, concepts pertaining to policy,
      the state, and health, and changes in the central categories from the various
      studies. Their analysis of this history indicates a reshaping of the theoretical
      frame of reference, giving greater flexibility to the structural determinism and
      macrosocial approach characterizing a major portion of academic production in the
      context from which the field emerged and thereby questioning the hegemony of the
      Marxist paradigm. In relation to more recent production, the authors emphasize
      the incorporation of new analytical references, thus providing greater complexity
      to the relationship between the social sciences and the field of Collective
      Health.

PMID- 9761607
TI  - [Poverty, demographic growth, and birth control: a critique of Peter Singer s
      ethical perspective on the relationship between rich and poor].
AB  - This article analyzes the relationship between population growth and ethical
      principles relating to poverty. The paper is a critical approach to the thesis
      presented by Peter Singer in his book Practical Ethics. The first part briefly
      examines the principal topics of his thesis. The author then analyzes the basis
      of Singer's theory with respect to the following questions: 1. Is overpopulation
      the main reason for poverty? Is it possible to establish an association between
      the poverty phenomenon and population growth? 2. Is Singer s demographic
      perspective valid? 3. Can problems of resource distribution be ignored when
      talking about poverty from an ethical perspective? 4. Is it true that birth
      control policy was successfully implemented in Mexico, Colombia, and Brazil? 5.
      Does Singer s position on population growth have a negative influence on the
      "collective imagination"? The paper concludes by suggesting some useful arguments
      for understanding an ethical perspective towards poverty.

PMID- 9761609
TI  - [Methodological issues in epidemiological studies of repetitive strain injuries].
AB  - Repetitive strain injuries (RSI) are a major public health problem with social
      and economic repercussions. This article presents a critical review of the
      published literature on RSI. The vast majority of the studies conducted in the
      last two decades were cross-sectional and exploratory. Results are difficult to
      interpret due to such methodological problems as lack of standardization and
      accuracy in identification of cases, inclusion of cases with potentially
      different diseases, varying levels of severity in the same study, lack of
      distinction between prevalent and incident cases, lack of precision in the
      definition and measurement of exposure, and confounding, besides the built-in
      constraint of cross-sectional studies for inferring causality. Some of these
      problems result from our insufficient knowledge of upper-limb soft tissue
      disorders and the absence of reliable diagnostic tests. Such problems could be
      addressed by studies whose design considered and stratified cases according to
      certainty and specificity of diagnosis.

PMID- 9761610
TI  - [Secular trends in the stature of Brazilian Navy recruits born from 1940 and
      1965].
AB  - The present paper reports data on secular trends in the stature of Brazilian Navy
      recruits born from 1940 to 1965. The final sample included 3269 individuals aged
      18.00-18.99. Statistics performed were: ANOVA (one-way and two-way), Sheffe test,
      simple linear regression between stature and year of birth, and multiple linear
      regression adjusting for level of schooling (beta coefficient) and chi-square.
      Results indicated a progressive growth trend in stature of 0.1 cm/yr. for the
      country as a whole. The trend was also observed for nearly all regions and two
      out of three levels of schooling and can be explained by improvement in some of
      the country's health indicators. One important characteristic was a higher level
      of schooling observed among Navy recruits, suggesting that these individuals
      represent a highly select group, and that therefore data on the Navy cannot be
      applied directly to the Brazilian population as a whole.

PMID- 9761611
TI  - [Trends in HIV/AIDS-related knowledge, attitudes, and practices in a Rio de
      Janeiro slum population].
AB  - The study aims to evaluate the present stage of knowledge, attitudes, and
      behavior related to HIV/AIDS in the population of Rio de Janeiro's Rocinha slum,
      the target of a control program over the last 6 years. We interviewed two hundred
      and ten people of both sexes, ranging from 13 to 49 years of age, and the results
      were compared with those of a study conducted in 1990 with the same methodology
      and sample size. The analysis showed an association between single males and more
      preventive behavior. Misconceptions about the role of mosquito bites and blood
      donation in the transmission of HIV persist, almost in the same proportion.
      Comparing the two samples, there was a significant increase in the role of
      HIV/AIDS education provided by schools, and the study also identified an increase
      in the rates and regularity of condom use. More efforts should be made to reduce
      misconceptions about HIV transmission and the vulnerability of couples. The study
      also highlights the need for more consistent policies related to condom
      distribution to the general population.

PMID- 9761612
TI  - [Health promotion and education: a diagnosis of sanitation conditions using
      participatory research and community education (Sao Joao dos Queiroz -
      Quixada/Ceara, Brazil)].
AB  - This study was conducted in a rural community, Sao Joao dos Queiroz, a township
      in the county of Quixada, Ceara, Brazil, using a combination of participatory
      research and community education in compliance with the health promotion
      reference and principles of the 1986 Ottawa Charter. The project was joined by
      representatives of several local government institutions and organizations from
      the grassroots community movement. The theme generating the research, as defined
      by an assembly meeting of the community association, was a diagnosis of
      sanitation conditions in the community. The starting point was the assessment of
      local conditions. Results showed adverse local conditions in sanitation,
      literacy, income, and employment. Suggestions for solving the problems were
      organized so as to be included in the planning agenda for local health policies.
      Evaluation was procedural and enriched with daily research activities. The
      problem-solving pedagogical approach developed during the educational process
      contributed to a critical reconstruction, appropriation, and sharing of the
      resulting knowledge.

PMID- 9761613
TI  - [Linkage of environmental and health data: health risk analysis of the Rio de
      Janeiro water supply by using geographical information systems].
AB  - Exposure assessment of population groups is based on linkage of environmental and
      health data. This relationship can be hard to establish due to spatial and
      temporal lags in data sets. Environmental data generally refer to scattered
      sampling points, while epidemiological data integrate periods of time within
      administrative territories. GIS can be used as a basis for organizing health
      related and environmental data sets. We examined potential health risk in the Rio
      de Janeiro city water supply based on the overlay of information layers
      containing data on the presence and quality of water supply services. We used
      census tracts as the primary georeferenced data, since they contain information
      on how households are supplied, water supply pipes, sources, and reservoirs, and
      water quality according to the monitoring program. Population groups exposed to
      risks were located and quantified using spatial operations among these layers and
      adopting different risk criteria. The main problems related to water supply are
      located on the northern slope of the Tijuca Mountain Range (involving the absence
      or poor quality of water) and in the western area of the city of Rio, where the
      population relies on alternative water supply sources. The different origins,
      objectives, and structures of data have to be analyzed critically, and GIS can be
      used as a data validation tool as well as an instrument for detailed
      identification of inconsistencies.

PMID- 9761614
TI  - [Identifying areas of epidemiological stratification in an onchocerciasis focus
      in Yanomami territory, Roraima, Brazil].
AB  - In this paper, aimed at suitable planning, analysis, and follow-up of treatment,
      control, and eradication in a human onchocerciasis program, were studied 27
      geographic areas and examined 3,974 inhabitants. Four epidemiological areas with
      different prevalences were identified and stratified.

PMID- 9761616
TI  - [An anthropological investigation of old age and concepts concerning arterial
      hypertension].
AB  - Anthropology and sociology are joining epidemiology, clinical investigation, and
      pathophysiology in studies on the aging process of the Brazilian population. The
      objectives of the present study were: a) to identify the concepts of the elderly
      population of the municipality of Araraquara, Sao Paulo, Brazil, towards the
      etiology of arterial hypertension (AH) and the relevance of the different signs
      and symptoms that accompany the disease; b) to improve elderly people's concepts
      towards the relevance and utilization of different treatment categories for AH.
      Structured interviews were conducted with 29 individuals, the majority aged 60
      years or over, who were being treated for hypertension at the Araraquara
      municipal gerontology outpatient clinic in August 1996. Patients were properly
      informed by the health team about problems related to AH, as clearly perceived in
      the discourse of the elderly. Folkloric concepts pertaining to etiology also
      appeared in the interviews and should be taken into consideration in the
      implementation of health education activities. Care provided by an
      interdisciplinary team was valued by the elderly. The most frequent complaint was
      the lack of free distribution of prescription medication for AH at the clinic.

PMID- 9761615
TI  - [Surveillance of phytotherapeutic drugs in the state of Minas Gerais. Quality
      assessment of commercial samples of chamomile].
AB  - Marketing of medicinal plants and phytotherapeutic products is spreading all over
      the world. In order to assess the commercialization of medicinal plants and
      phytotherapeutic products in the State of Minas Gerais, we identified and tested
      for the presence of adulterants and active ingredients in 27 samples of
      chamomile. All the samples consisted of Matricaria recutita flowers, but they
      were badly fragmented, a result of excessive handling and poor preservation. All
      samples contained contaminants, and insects were observed in 63% of the samples
      sold in drugstores. Only 50% of the samples in each group had the essential oils
      needed to produce antiinflammatory activity. Flavonoids and other phenolic
      constituents with a spasmolytic effect were detected in only 20% of the samples
      from each group. Results with chamomile indicated the poor quality with which
      medicinal plants and phytotherapeutic products are marketed and confirm the need
      for surveillance of such products in Brazil.

PMID- 9761617
TI  - [Quality control in primary health care. I - Consumer satisfaction].
AB  - In this paper, the first of a series dealing with the development of a
      methodology for assessing quality of ambulatory care, a sample of 270 outpatients
      from the same health center were presented with a list of 12 questions. Although
      different versions of the questionnaire were tested, we found a high degree of
      agreement between the results. The findings indicate that the parameter
      "satisfaction" lends itself readily to measurement, thus becoming a useful
      instrument for guiding active intervention.

PMID- 9761618
TI  - [An alternative for brazilian nutritional policy?].
AB  - This article focuses on the alternative nutrition policy as a public policy
      issue. It discusses such important and controversial questions as the efficacy
      and safety of multimixture. It also analyzes six epidemiological studies focusing
      on the evaluation of the reliability of results. The article concludes that the
      numerous ambiguities, gaps, and contradictions in knowledge concerning
      alternative nutrition do not support the incorporation of this intervention
      proposal as a food and nutritional policy for Brazil.

PMID- 9761620
TI  - [Hunger and mental illness].
AB  - Based on a recently-published article on the triad of drought, hunger, and mental
      illness, in which the main idea is that destitution may be leading to behavioral
      disorders in the drought-plagued population of the Brazilian Northeast, we
      reflect on what this so-called 'madness' may represent for this group of people.
      We attempt to analyze the issue from various disciplinary perspectives, going
      beyond merely causal explanations and taking into account that the reported
      disorders entail meanings following the articulation of cognitive, affective, and
      experiential elements founded on the social and cultural relations of
      individuals. From this point of view, the respective discourse assumes other
      interpretations, showing that illness is a singular process of construction.

PMID- 9761619
TI  - [Foucault, Derrida, and the history of madness: notes on a controversy].
AB  - The publication of the book Folie et Deraison. Histoire de la Folie a l'Age
      Classique (1961), by Michel Foucault, sparked a debate between the author and
      philosopher Jacques Derrida during the 1960s and 70s. Derrida criticized the
      methodological proposal and organization of the History of Madness presented by
      Foucault in the foreword to the first edition. The controversy appears to have
      motivated the author to withdraw this same foreword from the second edition. The
      purpose of this article is to analyze some current points in this controversy. It
      also presents a research agenda for an understanding of the reasons leading
      Foucault to take this stance.

PMID- 9761621
TI  - Analysis of the Multilayer Thickness Relationship for Water Vapor and Nitrogen
      Adsorption.
AB  - Six silica gels, where each gel had a characteristic calibrated pore size (40
      4000 A), have been characterized both by water vapor and nitrogen adsorption
      isotherms. From these results, it was concluded that two-thirds of the silica
      surface is hydrophobic. The selection of wide pores (>300 A) has enabled the
      determination of both the water and nitrogen t-curves for porous silica. It was
      observed that the development of the multilayer was identical in the wide pores
      irrespective of their size between 300 and 4000 A. The porous silica t-curve for
      water coincided exactly with the t-curve of nonporous adsorbents provided that
      their BET C constants were similar. For nitrogen t-curves, a matching BET C
      constant ensured similarity only in the monolayer region, above which divergence
      progressively increased, becoming important close to saturation. The effect of
      the t-curve choice on the pore size distribution was established. A t-curve
      displaying reduced adsorption had a tendency to shift the pore-size distribution
      to lower dimensions, toward the micropore region. As a consequence, the cumulated
      surface area obtained from the BJH model gave increasingly higher values than the
      BET nitrogen surface area. However, the pore-size distribution was shifted to
      higher pore sizes when the selected t-curve was above the natural t-curve. Errors
      as much as 25% were detected for the mean pore radius and cumulated surface area
      for certain literature t-curves. A comparison of the water and the nitrogen t
      curves indicated a crossover point when the water multilayer thickness became
      greater than the nitrogen thickness. Such behavior lends support to the
      cooperative adsorption mechanism for water vapor once a fixed number of water
      molecules (two layers) are present on the surface. Copyright 1998 Academic Press.

PMID- 9761622
TI  - Electrorotation of Deformable Fluid Droplets.
AB  - An equilibrium phase separated ternary system of polystyrene
      (PS)/polydimethylsiloxane (PDMS)/p-xylene was prepared, and the PS-rich phase was
      dispersed as droplets in a matrix of the PDMS-rich phase. The system was placed
      between vertical electrodes and the droplets rotated around a vertical axis
      perpendicular to the electric field direction in 4-8-kV cm-1 DC fields; in 2-4-kV
      cm-1, 0.1-Hz AC fields; and in 4-kV cm-1, 1-MHz AC fields, in some cases
      stopping, restarting, and changing the direction of rotation. They rotated less
      than a quarter of a turn back and forth in 1-10-Hz, 2-4-kV cm-1 fields and did
      not rotate at all in 1-kHz fields. Rotational velocities measured in the DC field
      were in agreement with an existing theory; those measured in the 0.1-Hz AC field
      and estimated in the 1-MHz AC field were in direct disagreement with a different
      existing theoretical treatment. When the PDMS-rich droplets were dispersed into a
      matrix of the PS-rich phase, the droplets elongated in the field direction in a 2
      kV/cm, 0.1-Hz electric field. Occasionally a portion of the matrix phase broke
      off into the PDMS-rich droplet, rotated for a while, and then rejoined the matrix
      phase. Copyright 1998 Academic Press.

PMID- 9761623
TI  - Discrete Charge Distributions in Dielectric Droplets.
AB  - The electrospray ion source has recently revolutionized mass spectrometry by
      allowing researchers to produce gaseous ions of very large molecular weights such
      as proteins and polymers. The process by which these high-molecular-weight ions
      are produced, however, is not very well understood. The purpose of the present
      work is to study the fields in the vicinity of each charge in order to shed some
      light on the ion formation process for charged dielectric droplets. An important
      feature of this work, therefore, is the treatment of the charge as discrete
      rather than continuous. The picture that emerges is of discrete charges in a
      dielectric droplet thermally oscillating around a potential well, located
      slightly below the droplet surface. The charges produce localized electrostatic
      pressures on the droplet surface that are higher (15.5 and 70% for dielectric
      constants of 80 and 20, respectively) than expected if the charge distribution
      were continuous. These high localized pressures could locally stretch the surface
      and result in the emission of ions or small charged droplets. The magnitude of
      these localized pressures is a function of the number of charges and the
      dielectric constant of the droplet. Copyright 1998 Academic Press.

PMID- 9761624
TI  - Anodic Surface Treatment on Carbon Fibers: Determination of Acid-Base Interaction
      Parameter between Two Unidentical Solid Surfaces in a Composite System.
AB  - An interpretation based on more precise linear free energy relationships is
      proposed for the determination of the acid-base interaction of a solid surface,
      in the context of inverse gas chromatography at infinite dilution. This work
      leads to the evaluation of acid-base interaction parameter, Ia-b, between two
      constitutive elements in a composite system. In this work, the acid-base
      interaction parameters between fibers and matrix are greatly correlated with the
      results of the interfacial shear strength carried out on single fibers and the
      interlaminar shear strength of the composites. As an experimental result,
      electrochemical treatment of fiber surfaces significantly appears essential to
      the improvement of the acid-base character in a way expected from the nature of
      the electrolytes used during the treatment. Copyright 1998 Academic Press.

PMID- 9761625
TI  - Surface Behavior of Spread Sodium Eicosanyl Sulfate Monolayers.
AB  - The surface behavior of spread sodium eicosanyl sulfate monolayers is
      characterized by determining the dilational moduli from different pi/A isotherms
      and from surface stress relaxation experiments in the short-time range (<10 min).
      The elasticities derived from the pi/A isotherms differ depending on the
      experimental conditions. The quasi-equilibrium isotherm displays a plateau in the
      range of coexistence of the condensed and the expanded phases and strong
      increases caused by the formation of a solid-like phase. In contrast,
      nonequilibrium pi/A isotherms yield effective elasticities showing a maximum
      within the phase coexistence range. The formation of a solid phase cannot be
      detected because of the onset of monolayer collapse. Different stress relaxation
      experiments were carried out for monolayer compression and dilation using
      transient drop volume jumps. Depending on the experimental run, these experiments
      lead to consistent and complementary results with those derived from pi/A
      isotherms under comparable conditions. The stress recoveries yield a relaxation
      time, a dilation viscosity, and a parameter characterizing the homogeneity of the
      relaxation process. The stress relaxation is interpreted accounting for both the
      nonequilibrium between the monolayer and the bulk phase and the nonequilibrium
      within the monolayer. The influence of alkylsulfate hydrolysis on the presented
      results was checked. It was found that within the time scale of the experiments
      no influence of hydrolysis could be detected. Copyright 1998 Academic Press.

PMID- 9761626
TI  - Low-Rate Dynamic Contact Angles on Poly(methyl methacrylate) and the
      Determination of Solid Surface Tensions.
AB  - Low-rate dynamic contact angles of nine liquids on a poly(methyl methacrylate)
      (PMMA) polymer are measured by an automated axisymmetric drop shape analysis
      profile (ADSA-P). It is found that two liquids dissolved the polymer on contact.
      From the experimental contact angles of the other seven polar and nonpolar
      liquids, it is found that the liquid-vapor surface tension times cosine of the
      contact angle changes smoothly with the liquid-vapor surface tension (i.e.,
      gammalnucos theta depends only on gammalnu for a given solid surface). The
      dependence of gammalnucos theta on gammasnu is explicitly illustrated by
      replacing the solid surface from the PMMA to other methacrylate polymers: such a
      procedure shifts the curves in a very regular manner. Thus, because of Young's
      equation, gammasl depends only on gammalnu and gammasnu. This contact angle
      pattern is in harmony with those from other inert and noninert (polar and
      nonpolar) surfaces. The solid-vapor surface tension of PMMA calculated from the
      equation of state approach for solid-liquid interfacial tensions is found to be
      38.5 mJ/m2, with a 95% confidence limit of +/-0.5 mJ/m2 from the experimental
      contact angles of the seven liquids. Copyright 1998 Academic Press.

PMID- 9761627
TI  - New Carbon-Silica Composite Adsorbents from Elutrilithe.
AB  - Carbon-silica composite adsorbents with high surface area and pore volume were
      prepared from natural elutrilithe. The elutrilithe was chemically activated with
      K2CO3 at 1123 K and then dissolved in water. The textural and adsorptive
      properties of the composite adsorbents can be adjusted by varying the pH and
      concentration of the sol mixture and the gel aging temperature. Composite
      adsorbents prepared at low concentration have high adsorption capacities for both
      water (43.4%) and cyclohexane (32.0%), exceeding those of ordinary commercial
      silica gel and active carbon. The adsorbents prepared at high concentration are
      more hydrophobic in nature, with adsorption capacities for water and cyclohexane
      of 18.5 and 41.5%, respectively. The composite adsorbents are resistant to
      repetitive adsorption and regeneration cycles. Copyright 1998 Academic Press.

PMID- 9761628
TI  - Changes in Hydration Properties of Silica Gel in a Process of Its Carbonization
      by Pyrolysis of Acetylacetone Zn (Ti) Acetylacetonates.
AB  - Changes in hydration properties of different compounds in a process of formation
      of a complex adsorbent comprising carbon and TiO2 or Zn2SiO4 on its surface were
      studied by 1H NMR spectroscopy under conditions of a liquid phase freezing.
      Adsorbents were synthesized on the basis of a mesoporous silica gel, the surface
      of which was covered with a carbon layer formed in a process of a high
      temperature pyrolysis of acetylacetone. Titanium oxide and zinc silicate on the
      surface of a parent silica gel were formed by a pyrolysis of acetylacetonates of
      the corresponding metals. It has been revealed that the main types of surface
      active sites for the adsorbed water molecules on the carbosil surface are the
      systems of condensed benzene nuclei of a carbon component of the surface and
      hydroxyl groups of silica surface. Zn2SiO4 and TiO2 have been formed in a process
      of pyrolysis of the corresponding metal acetylacetonates. Water bound with the
      oxide component of the carbosil surface exceeds 80% of the total amount of the
      adsorbed water. The carbon component of the surface is localized mainly in the
      narrowest pores. A minimum value in the free surface energy was recorded for the
      carbosil sample. Copyright 1998 Academic Press.

PMID- 9761629
TI  - A Study of the Aggregation Behavior of Hexyltrimethylammonium Bromide in Aqueous
      Solution.
AB  - The self-association of n-hexyltrimethylammonium bromide (C6TAB) in aqueous
      solution has been examined as a function of temperature and electrolyte
      concentration. The critical micelle concentration (CMC) and the degree of
      counterion binding (beta) were determined by conductivity measurement at
      temperatures over the range 288.15-318.15 K. Ultrasound velocity measurements
      were used to obtain the CMC in water and in a range of concentrations of
      electrolyte (0.1 to 0.6 mol kg-1 NaBr) and static light scattering to obtain the
      aggregation number and the degree of counterion binding in water at 298.15 K. The
      enthalpy change on micellization in water was measured by microcalorimetry.
      Apparent adiabatic compressibilities were calculated from a combination of
      density and ultrasound velocity measurements. Changes in the thermodynamic
      properties on micellization were determined by applying the mass action model;
      good agreement was found between experimental and theoretical enthalpy changes.
      From comparison with the properties of other n-alkyltrimethylammonium bromides it
      has been shown that the CMC of C6TAB in water is lower than that predicted from
      the linear relationships between CMC and the number of carbon atoms in the alkyl
      chain. Similarly, the standard Gibbs energy of micellization is less negative
      than predicted, and the degree of counterion binding is much lower than for other
      CnTABs. It is suggested that the anomalous behavior of C6TAB is a consequence of
      the more highly organized core of the aggregates of very low aggregation number
      (3-4) and the high degree of exposure of the micellar components to the aqueous
      environment. Copyright 1998 Academic Press.

PMID- 9761630
TI  - Effect of Polyoxybutylene Chain Length on the Surface Activity of Butylene Oxide
      Ethylene Oxide Block Copolymers.
AB  - Block copolymer surfactants (RBE) obtained by the addition of ethylene oxide to n
      butyl, n-hexyl, n-octyl, and n-decyl ethers of mono- to tetrabutylene glycol are
      described. The surface activity of these nonionic surfactants has been
      determined, i.e., critical micelle concentration (CMC), surface excess
      concentration, Gamma, surface area demand per molecule, A, surface tension at
      CMC, gammaCMC, and DeltaG degreesads. A linear decrease of log CMC vs number of
      oxybutylene units in a copolymer molecule is observed. The change in the work of
      cohesion per oxybutylene group when passing from a molecular into a micellar
      state, calculated from the Shinoda equation, is 0.99-0.92 kT for the studied
      compounds. The equivalent of CH2 in the aliphatic alcohol group is 1.06-1.15
      oxybutylene units. Surface properties of these surfactants, i.e., cloud point,
      wetting ability, contact angle, and foam height, have also been determined.
      Copyright 1998 Academic Press.

PMID- 9761631
TI  - Effect of Surface Mobility on Collision of Spherical Drops.
AB  - The collision of two spherical liquid drops is considered which allows the effect
      of coalescence on the formation and stability of dispersions to be studied. An
      analytical solution is derived for the variation in the hydrodynamic force with
      the approach velocity and the separation thickness during the impact in terms of
      the drop diameter, allowing for the effect of induced flow inside the drops.
      Setting this force equal to the rate of change of momentum of the drops enables
      the variation with time in the separation between the drops to be obtained in
      terms of the initial approach velocity, drop diameter, and viscosity ratio. The
      analysis also yields the time variation in the force and approach velocity. For a
      given impact velocity, the separation thickness decreases with time until a
      minimum value is reached, which decreases as the impact velocity and the
      viscosity ratio of the continuous and dispersed phases increase. Previous authors
      have only obtained the variation in the approach velocity with the unknown
      variable force and separation thickness during the impact and therefore could not
      obtain the variation in the separation thickness with time. Knowing this
      variation enables the possibility of coalescence during impact to be
      investigated. Coalescence is influenced by the minimum separation thickness
      attained at low impact velocities and by drop deformation and inertial drainage
      at high velocities. Copyright 1998 Academic Press.

PMID- 9761632
TI  - Removal of Fluoride from Aqueous Solution by Using Alum Sludge.
AB  - The ability of treated alum sludge to remove fluoride from aqueous solution has
      been investigated. The studies were carried out as functions of contact time,
      concentration of adsorbent and adsorbate, temperature, pH, and effect of
      concentrations of other anions. The data indicate that treated alum sludge
      surface sites are heterogeneous in nature and that fits into a heterogeneous site
      binding model. The optimum pH for complete removal of fluoride from aqueous
      solution was found to be 6. The rate of adsorption was rapid during the initial 5
      minutes, and equilibrium was attained within 240 minutes. The adsorption followed
      first-order rate kinetics. The present system followed the Langmuir adsorption
      isotherm model. The loading factor (i.e., the milligram of fluoride adsorbed per
      gram of alum sludge) increased with initial fluoride concentration, whereas a
      negative trend was observed with increasing temperature. The influence of
      addition of anions on fluoride removal depends on the relative affinity of the
      anions for the surface and the relative concentrations of the anions. Copyright
      1998 Academic Press.

PMID- 9761633
TI  - Removal of Organic Films From Rotating Disks Using Aqueous Solutions of Nonionic
      Surfactants: Effect of Surfactant Molecular Structure.
AB  - In prior work, we examined the removal of abietic acid films from rotating
      fiberglass laminate disks by aqueous solutions of a nonionic surfactant. A three
      stage cleaning mechanism was found, consisting successively of solubilization,
      shear-driven cleaning, and roll-up. We extend this work by exploring the
      influence of the surfactant molecular structure on the kinetics of the cleaning
      process. Five different poly(ethylene glycol) alkyl ether surfactants (CxEy) were
      used. Both the alkyl (x) and ethoxy (y) chain lengths were varied. Not all of the
      surfactants exhibited a three-stage cleaning mechanism. It was found that for
      surfactants with relatively high solubilization rates, the shear-driven cleaning
      stage did not occur. The selection of the most efficient surfactant depends on
      whether the surfactant concentration is below or above its critical micelle
      concentration (CMC). At submicellar concentrations, faster cleaning is obtained
      by surfactants that can induce shear-driven removal. At concentrations above the
      CMC, it is found that surfactant efficiency for a fixed alkyl or ethoxy chain
      length increases as the surfactant becomes more hydrophilic. This is attributed
      in part to the lower viscosity that the film achieves with the more hydrophilic
      surfactants due to their partitioning into the film, as well as their ability to
      carry water into the film. Copyright 1998 Academic Press.

PMID- 9761634
TI  - Influence of Surfactant Structure on the Drainage of Nonionic Surfactant Foam
      Films.
AB  - The stability of vertical liquid films produced from aqueous solutions of
      polyoxyethylene alkyl ether (CnEm) was studied by monitoring the dynamic surface
      tension (gammat) and aqueous core thickness of a vertical foam film (d2) measured
      by FT-IR. The temperature dependence of the drainage patterns of the liquid films
      was clarified for CnE8 (n = 10, 12, 14, and 16) solutions. It was found that the
      critical thickness (Drup) where the film rupture happens increased with
      increasing temperature in the case of C10E8 and C12E8, while Drup remarkably
      decreased and finally formed a black film in the case of C14E8 and C16E8
      solutions within the measured temperature range. In addition, a delay in the film
      drainage occurred in these systems, which was caused by the stabilization of the
      films via the Marangoni effect proved by dynamic surface tension measurements. On
      the other hand, heterogeneous ethoxylated dodecyl ethers (C12Em) modified with a
      hydrophilic group showed a remarkable increment of Drup under dynamic conditions
      without the Marangoni stabilization in the foam film. Adding a hydrophobic group
      at the end of the polar head produces a large area per molecule and causes a
      large increase in the surface coverage of the air bubbles. However, a less
      structured surface coverage facilitated the breaking of the foam during the Ross
      and Miles test. These results indicate that under dynamic conditions, the
      Marangoni effect and the hydrophobic interaction at the surface become important
      for foam film rupture. Copyright 1998 Academic Press.

PMID- 9761635
TI  - Acid-Base Properties and Heavy and Alkaline Earth Metal Adsorption on the Oxide
      Solution Interface: Non-Electrostatic Model.
AB  - A new approach was applied to the description of acid-base properties and heavy
      and alkaline earth metal adsorption on the oxide-solution interface. The acid
      base properties of hematite have been determined at different temperatures. The
      adsorption of protons and hydroxyl ions on the hematite surface has a temperature
      independent character. The proton and hydroxyl ion adsorption in NaCl media was
      explained by the reactions. &tbond;H2O + H3O+ + Cl- = &tbond;H2OHCl + H2O
      &tbond;OH2 + OH- + Na+ = &tbond;OHNa + H2O. The modified equation of the Frumkin
      Fouler-Guggenheim isotherm was used to simulate the experimental data (theta,
      relative adsorption): log[thetaHCl/(1 - thetaHCl)] - log[H+] - log[Cl-] = log
      KoHCl + log BH[NthetaHCl/(1 + (N - 1)thetaHCl)]; log[thetaNaOH/(1 - thetaNaOH)] -
      log[Na+] - log[OH-] = logKoNaOH + logBOH[NthetaNaOH/(1 + (N - 1)thetaNaOH)]. The
      model parameters were log BH = -4.92 +/- 0.1, log BOH = -2.61 +/- 0.05, N = 3.25
      +/- 0.2. The site density of the hematite surface was determined to be 3.8 +/-
      0.1 u moles/m2. The values of the constants were log KoHCl (25-100 degreesC) =
      9.50 +/- 0.1; log KoNaOH (25-100 degreesC) = 5.93 +/- 0.1. Copyright 1998
      Academic Press.

PMID- 9761636
TI  - Study of Copper Complexes Absorbed on a Silica Gel Surface Chemically Modified
      with 5-Amino-1,3,4-thiadiazole-2-thiol.
AB  - The isotherms of adsorption of CuX2 (X = Cl-, Br-, ClO-4) by silica gel
      chemically modified with 5-amino-1,3,4-thiadiazole-2-thiol were studied in
      acetone and ethanol solutions, at 25 degreesC. The following equilibria constants
      (in L mol-1) were determined: (a) CuCl2, 3.2 x 10(3) (ac), 2.5 x 10(3) (eth); (b)
      CuBr2, 2.9 x 10(3) (ac), 2.3 x 10(3) (eth); (c) Cu(ClO4)2, 1.8 x 10(3) (ac), 1.2
      x 10(3) (eth); ac, acetone; eth, ethanol. The electron spin resonance spectra of
      the surface complexes indicated a tetragonal-distorted structure in the case of
      lower degrees of metal loading on the chemically modified surface. The d-d
      electronic transition spectra showed that for the ClO-4 complex, the peak of
      absorption did not change for any degree of metal loading and for Cl- and Br-
      complexes, the peak maxima shifted to higher energy with lower metal loadings.
      Copyright 1998 Academic Press.

PMID- 9761637
TI  - Electrostatic Interactions in Adsorbed Protein Layers Probed by a Sedimentation
      Technique.
AB  - A simple centrifugation technique has been used to determine the thicknesses of
      layers of alphaS1-casein and beta-casein adsorbed onto monodisperse polystyrene
      latex particles. The influence of electrostatic interactions within the layers on
      their thickness and stabilizing ability is investigated by varying the ionic
      strength of the suspension or by including calcium ions, known to bind
      specifically to the caseins. Copyright 1998 Academic Press.

PMID- 9761638
TI  - The Effects of Flocculation on the Propagation of Ultrasound in Dilute Kaolin
      Slurries.
AB  - A broadband ultrasonic spectrometer has been used to measure ultrasonic
      attenuation and phase velocity dispersion as functions of frequency in kaolin
      suspensions over a range of solid volume fractions from phi = 0.01 to phi = 0.08
      and over a pH range from 3 to 9. The Harker and Temple theory was used to
      simulate ultrasound propagation in the suspension, using measured slope
      viscosity, particle size, and size distribution. Simulated results for ultrasonic
      attenuation and phase velocity agree well with measured values. Both sets of
      results agree well and show that for volume fractions above phi approximately
      0.05 attenuation and velocity dispersion increase for increasing floc size,
      whereas for volume fractions below phi approximately 0.05 attenuation and
      velocity dispersion both decrease. It is proposed that the mechanism for this
      change in behavior around phi approximately 0.05 involves changes in floc density
      and floc size distribution with phi and pH. Copyright 1998 Academic Press.

PMID- 9761639
TI  - Aggregation Behavior of Sugar Surfactants in Aqueous Solutions: Effects of
      Temperature and the Addition of Nonionic Polymers.
AB  - The aggregation behavior, critical micelle concentration (cmc) and micelle
      aggregation number (N), of dodecyl maltoside (DM), octyl glucoside (OG), and
      Hecameg has been investigated in water and in water plus one of the three water
      soluble polymers, polyoxyethylene (POE), polyoxypropylene (POP), and polyvinyl
      pyrrolidone (PVP), by means of florescence probing and time-resolved fluorescence
      quenching. The cmc of DM in water increased with temperature and showed a slight
      increase in the presence of POE. The aggregation number N of DM micelles was
      nearly independent of concentration (0.25-1 wt %) and temperature (16-60
      degreesC). It remained invariant upon addition of 2 wt % POE or PVP but decreased
      slightly upon addition of the more hydrophobic POP. With increasing temperature,
      the cmc of OG decreased, went through a shallow minimum at around 35 degreesC,
      and increased. Addition of POE slightly increased the cmc in the whole
      temperature range. The aggregation number of OG micelles showed a fairly flat
      maximum at around 30 degreesC, and was unaffected by the presence of 2 wt % POE
      or PVP. However, N showed a complex dependence on temperature in the presence of
      POP, with lower values than in pure water below 15 degreesC, and rapidly
      increasing quencher-dependent values above this temperature. Hecameg was
      characterized by N-values nearly independent of temperature and concentration.
      Intermicellar exchanges of probe and/or quencher were observed with OG and
      Hecameg, but not with DM. The above results are compared to those for the
      nonionic ethoxylated surfactants. The effect of various parameters on the micelle
      aggregation number, the micelle polydispersity, the occurrence of sugar
      surfactant/nonionic polymer interactions, and the mechanisms responsible for the
      observed intermicellar exchanges are discussed. Copyright 1998 Academic Press.

PMID- 9761640
TI  - 1H NMR Self-Diffusion in Polymer-Surfactant Nanocapsules and Cryogels with
      Enzyme.
AB  - The multicomponent self-diffusion in nanocapsules and cryogel biocatalytic
      systems containing alpha-chymotrypsin has been studied with the NMR-PGSE method
      at various temperatures and compared with the diffusion of such systems without
      enzyme. Unilamellar vesicles have been formed in water after "coating" with Brij
      97 of the poly-(N,N-diallyl-N,N-didodecyl ammonium bromide), poly-DDAB,
      nanocapsules. The latter have been obtained by UV-irradiation of reversed
      hydrated micelles from DDAB in cyclohexane. Cryogels were made from poly(vinyl
      alcohol), PVA, aqueous solutions by a freezing-thawing cyclic process. Both
      compartmented systems were used as vehicles of the enzyme entrapped in inner
      aqueous cavities. The activation energies of self-diffusion for both these
      systems have been calculated. These data contain information concerning
      morphology and molecular packing. Encapsulation of alpha-chymotrypsin in the poly
      DDAB/Brij-97 vesicles and the PVA cryogel lowers the Ds values for all molecules
      and shifts the cloud point toward the lower temperature. On the contrary, the
      syneresis point for the PVA cryogel is shifted for 8 degrees toward the higher
      temperature by the entrapment of the enzyme. Besides, entrapment of alpha
      chymotrypsin in the cryogel promotes the increase of the Ea values for the PVA
      chain on 1.5 kJ/mol below the syneresis point. Such a difference indicates the
      influence of the H-bond system of PVA hydroxyl groups and water molecules on the
      interference of the protein globule. Entrapment of alpha-chymotrypsin leads to
      consolidation of this H-bond system. Copyright 1998 Academic Press.

PMID- 9761641
TI  - Compositional Homogeneity of Liposomal Membranes Investigated by Capillary
      Electrophoresis.
AB  - Capillary electrophoresis has been demonstrated to be a new powerful tool for
      investigating the compositional homogeneity of liposomal membranes composed of
      phospholipids and guest molecules. In the case of charged components distributed
      heterogeneously on membranes, electropherograms show several distinguishable
      peaks even with monodisperse size distributions of liposomes because each
      liposomal particle carries a different amount of charge. The heterogeneity of
      noncharged components, when the lipids and the guest components have
      significantly different molar absorptivities at two different wavelengths, can
      also be judged from the signal ratio observed at the two wavelengths using a
      photodiode array detector. This new method can be used for the quality control of
      liposomal products. Copyright 1998 Academic Press.

PMID- 9761642
TI  - The Role of Ionic Surfactants in Compression Dewatering of Alum Sludge.
AB  - This work has experimentally investigated the characteristics of filtration
      followed by consolidation dewatering of an alum sludge, with especial attention
      to the effects of adding ionic surfactants (SDS or CTAB). The filtration and
      consolidation stages at a pressure of 3000 psi were discussed separately. The
      efficiency of filtration is enhanced in the presence of surfactant molecules;
      however, the cationic surfactant (CTAB) raises the consolidation rate while the
      anionic surfactant (SDS) retards it. A newly proposed rheological model has been
      employed for interpreting the consolidation data. CTAB would not alter markedly
      the moisture distribution in the sludge, but SDS does increase markedly the
      amount of the tightly bound moisture by diminishing the portion occupied by pore
      water. The possible role of surfactants in the sludge flocs is considered. Both
      surfactants can be used as conditioning aids during the filtration stage.
      However, the applications of SDS to the consolidation stage are not encouraged.
      Copyright 1998 Academic Press.

PMID- 9761643
TI  - Effect of Interfacial Tension on the Formation of the Gradient Morphology in
      Polymer Blends.
AB  - In order to investigate the effect of interfacial tension on the formation of
      gradient phase morphology in polymer blends, a saponification reaction was
      carried out in this study to obtain several kinds of EVA with different contents
      of -OH groups. These EVAs with different -OH contents, namely with different
      polarities, were then blended with PP, and thus a series of PP/EVA blends with
      different interfacial tensions was obtained. The same initial droplet size could
      be obtained for PP/EVA blends with different interfacial tensions during
      compounding through adjusting the degree of saponification of EVA. It was found
      that all these PP/EVA blends could form a gradient morphology in the vertical
      section of the samples as PP/EVAc blends. Using a computer image analyzer, the
      vertical distributions of the dispersed droplet size and the EVAc component in
      each blend were determined. The results showed that the EVA droplet size and the
      EVA component increased in the vicinity of the sample surface with increasing
      interfacial tension of the blends; i.e., the greater the interfacial tension
      between PP and EVA, the larger the gradient tendency in the blend. Copyright 1998
      Academic Press.

PMID- 9761644
TI  - Effect of Nonionic Surfactant on the Deformation and Breakup of a Drop in an
      Electric Field.
AB  - We have examined deformation and breakup of fluid drops suspended in another
      immiscible fluid under the action of an electric field. The contiguous fluids are
      incompressible Newtonian and the fluid-fluid interface is populated by nonionic
      surfactant molecules. The presence of the nonionic surfactant affects both the
      degree of deformation and the modes of breakup through the so-called Marangoni
      flow resulting from its nonuniform distribution on the interface. The drop is
      deformed into either a prolate or an oblate spheroid depending upon the
      electrical properties of the fluids and sustains a steady-state shape until the
      electrical Weber number is above a certain critical value. Two distinctively
      different modes of the drop breakup are observed depending on the surfactant
      concentration. When the interface is clean or contaminated by a very small amount
      of surfactant molecules, the drop bursts into several small droplets after
      forming bulbous ends. There exists a certain range of the surfactant
      concentration in which tip-steaming is a prevalent drop breakup mode. If the
      surfactant concentration exceeds this range, the breakup mode goes back to the
      fragmentation with bulbous end formation. This shows that, although not
      pronounced in the small deformation limit, nonuniformity in the surfactant
      distribution is a decisive factor for the breakup mechanism of a prolate
      spheroid. The results also show that when the drop deforms into an oblate
      spheroid, the effect of nonuniform distribution of surfactant can be significant.
      Copyright 1998 Academic Press.

PMID- 9761645
TI  - Surface Structure and Properties of Calcium Hydroxyapatite Modified by
      Hexamethyldisilazane.
AB  - The surface of synthetic calcium hydroxyapatite Ca10(PO4)6(OH)2 (CaHAP) particles
      was treated by repeated modification with hexamethyldisilazane [(CH3)3Si]2NH
      (HMDS) in hexane and thermal treatment and the surface of the modified CaHAP was
      characterized by various means. No remarkable change in XRD patterns or in
      particle shape by the modification was observed. The width of the CaHAP particles
      gradually increased with repeating the modification. FTIR results indicated that
      HMDS reacted with surface P-OH groups of CaHAP to yield surface Si-(CH3)3 groups.
      The surface of the modified CaHAP was hydrophobic. The surface Si-(CH3)3 groups
      turned to three kinds of surface Si-OH groups by treating the modified materials
      at 500 degreesC in air. These formed surface Si-OH groups and the remaining
      surface P-OH groups reacted with HMDS by repeating the modification, resulted in
      the increase of the surface Si atoms. The modified material having surface Si
      (CH3)3 or Si-OH groups adsorbed much less CO2 than the unmodified one. Copyright
      1998 Academic Press.

PMID- 9761646
TI  - The Denaturation of Lysozyme Layers Adsorbed at the Hydrophobic Solid/Liquid
      Surface Studied by Neutron Reflection.
AB  - We have studied the adsorption of lysozyme layers at a hydrophobic silicon water
      interface using specular neutron reflection. The hydrophobic surface was obtained
      by self-assembly of a densely packed monolayer of octadecyltrichlorosilane (OTS)
      onto the natural silica layer on the smooth surface of a (111) silicon block. The
      effect of pH on the adsorbed lysozyme layer was examined at a constant lysozyme
      concentration of 0.03 g dm-3 and at a constant ionic strength of 0.02 M.
      Reflectivity profiles at different pH show that adsorption is irreversible with
      respect to pH, the composition and structure of the final layer being dependent
      on the route by which the pH was achieved. The adsorbed protein layer was found
      to divide into approximately two regions, a densely packed thin layer next to the
      OTS surface and a diffuse thicker layer extending into the bulk solution. None of
      the dimensions of this structure corresponds to those of the globular protein in
      solution, suggesting that, unlike its adsorption at the hydrophilic silica/water
      interface, lysozyme is denatured at the OTS/water surface. The irreversible
      adsorption is explained by the combined interaction of the hydrophobic attraction
      of the hydrophobic fragments in lysozyme to the OTS surface and electrostatic
      repulsion within the adsorbed layer. The hydrophobic surface induces the exposure
      of hydrophobic fragments from the lysozyme assembly. The thickness of the dense
      layer suggests that the denatured protein adsorbs in the form of peptide chains
      with the hydrophobic amino acid side chains attached to the OTS surface with the
      hydrophilic side chains extending into the bulk solution. Since lysozyme is more
      stable at pH 7 than at pH 4, the difference in initial adsorption is dominated by
      the greater relative stability of lysozyme to denaturation at the higher pH. A
      change of pH from 7 to 4 reduces the stability of the protein to unfolding and
      results in more adsorption than when the pH is changed in the opposite direction.
      Solution pH also affects the net charges within the hydrophilic tail region and
      the structural distribution of the tail region was found to vary with pH.
      Copyright 1998 Academic Press.

PMID- 9761647
TI  - Effect of Co-Adsorbed Surfactant on the Structure of Self-Assembled Monolayer of
      Thiol on Polycrystalline Gold.
AB  - The structure and formation kinetics of a self-assembled monolayer (SAM) of long
      chain alkane thiol in the presence and absence of an anionic surfactant like
      sodium dodecyl sulfate (SDS) has been studied using impedance, cyclic
      voltammetic, and quartz crystal microbalance (QCM) measurements. The comparison
      of these results, especially the ionic permeability of the monolayer, suggests a
      composite monolayer where both the surfactant and thiol molecules are
      cooperatively adsorbed to form distinct surfactant patches. This is further
      substantiated by the voltammetric experiments with redox probe in solution. A
      gradual change in the double layer capacitance value for the thiol monolayer
      alone (1.4 uF/cm2) to the composite monolayer (6.7 uF/cm2) and to the surfactant
      alone (11 uF/cm2) further supports the nature of the mixed monolayer. The
      kinetics of monolayer formation also shows interesting changes as revealed by the
      QCM studies, where a phase transition from simple to composite monolayer has been
      observed around an approximate coverage of 0.44. The same growth scheme is also
      observed for 1-pentanethiol, naphthalene disulfide, and diphenyl disulfide,
      suggesting that the mechanism appears to be general. Copyright 1998 Academic
      Press.

PMID- 9761648
TI  - Direct Determination of the Dependence of the Surface Shear and Dilatational
      Viscosities on the Thermodynamic State of the Interface: Theoretical Foundations.
AB  - Recent developments in nonlinear optical techniques for noninvasive probing of a
      surfactant influenced gas/liquid interface allow for the measurement of the
      surfactant surface concentration, c, and thus provide new opportunities for the
      direct determination of its intrinsic viscosities. Here, we present the
      theoretical foundations, based on the Boussinesq-Scriven surface model without
      the usual simplification of constant viscosities, for an experimental technique
      to directly measure the surface shear (us) and dilatational (kappas) viscosities
      of a Newtonian interface as functions of the surfactant surface concentration.
      This ability to directly measure the surfactant concentration permits the use of
      a simple surface flow for the measurement of the surface viscosities. The
      requirements are that the interface must be nearly flat, and the flow steady,
      axisymmetric, and swirling; these flow conditions can be achieved in the deep
      channel viscometer driven at relatively fast rates. The tangential stress balance
      on such an interface leads to two equations; the balance in the azimuthal
      direction involves only us and its gradients, and the balance in the radial
      direction involves both us and kappas and their gradients. By further exploiting
      recent developments in laser-based flow measuring techniques, the surface
      velocities and their gradients which appear in the two equations can be measured
      directly. The surface tension gradient, which appears in the radial balance
      equation, is incorporated from the equation of state for the surfactant system
      and direct measurements of the surfactant surface concentration distribution. The
      stress balance equations are then ordinary differential equations in the surface
      viscosities as functions of radial position, which can be readily integrated.
      Since c is measured as a function of radial position, we then have a direct
      measurement of us and kappas as functions of c. Numerical computations of the
      Navier-Stokes equations are performed to determine the appropriate conditions to
      achieve the requisite secondary flow. Copyright 1998 Academic Press.

PMID- 9761649
TI  - The Interfacial Polarization-Induced Electrorheological Effect.
AB  - The Wagner theory, which describes the interfacial polarization in heterogeneous
      systems, was employed to model the electrorheological (ER) effect under the
      presumption that the shear stress increment is induced by the interfacial
      polarization. The currently observed experimental facts, such as the yield stress
      of some ER fluids, decreases with the applied field frequency increasing or the
      environment temperature decreasing, while that of other fluids increases with the
      frequency decreasing or temperature increasing; the strongest ER effect is
      usually observed in the suspension with the dispersed particle conductivity
      around 10(-7) S/m; the particle dielectric loss tangent of a good ER fluid
      usually is above 0.10 at 1000 Hz; and the fluid with a high conductive particle
      usually has a short response time, can be satisfactorily understood with the
      extended Wagner model. The Wagner-polarization-induced maximum yield stress of a
      heterogeneous-type ER fluid is estimated around 7 kPa under the presumption that
      the dielectric constants of the solid particle and the liquid medium are 10 and
      2, respectively, the particle volume fraction is 35%, and the applied electric
      field strength is 3 kV/mm. It is concluded that the ER effect may substantially
      correlate with the Wagner polarization, which would help in understanding the
      mechanism of the ER effect and would provide a strategy for designing high
      performance ER fluids. Copyright 1998 Academic Press.

PMID- 9761650
TI  - The Interfacial Chemistry of the Grignard Reaction: The Composition of the Film
      Formed on Air-Exposed Magnesium.
AB  - X-ray photoelectron spectroscopy has been used to monitor the composition of the
      surface film formed when a clean Mg metal is subjected to pretreatments that
      simulate exposure to ambient environments. The results indicate that an as
      received (commercial) Mg metal contains a surface covered by a film constituted
      predominantly by magnesium hydroxide and a smaller but appreciable quantity of
      magnesium bicarbonate. These observations have important ramifications in the
      mechanistic description of the Grignard reaction since the interaction between Mg
      metal and an alkyl halide must contend with the surface hydroxide and bicarbonate
      films. Copyright 1998 Academic Press.

PMID- 9761651
TI  - Comparison of the Adsorption of o-Phthalate on Boehmite (gamma-AlOOH), Aged gamma
      Al2O3, and Goethite (alpha-FeOOH).
AB  - This work is concerned with the adsorption of o-phthalate (1,2
      benzenedicarboxylate) at the water-metal (hydr)oxide interface. Previously
      published infrared spectroscopic, potentiometric, and adsorption data
      characterizing the boehmite (gamma-AlOOH) system are compared with new data
      collected for o-phthalate adsorption on aged gamma-Al2O3 and goethite (alpha
      FeOOH). The study focuses on identifying bonding mechanisms, stoichiometries, and
      stabilities of the formed complexes, and comparing these among the three systems.
      Furthermore, the effects of ionic strength and composition of the ionic medium
      are investigated. The infrared spectroscopic data provided direct, molecular
      level evidence for the existence of two dominating surface complexes on all three
      solids. One was shown to be a deprotonated outer-sphere species and the other was
      an inner-sphere surface complex. The inner-sphere complexes on the three solids
      were structurally related, and they were tentatively assigned to a mononuclear,
      chelating structure involving both carboxylate groups. The outer-sphere complexes
      were shown to increase in relative importance at high pH and low ionic strengths,
      while low pH and high ionic strengths favored the inner-sphere complexes. The
      information gained from the infrared spectroscopic investigations was used as
      qualitative input in the formulation of the surface complexation models. New
      models, based on the extended constant capacitance approach, were presented for
      the o-phthalate/aged gamma-Al2O3 and o-phthalate/goethite systems. Copyright 1998
      Academic Press.

PMID- 9761652
TI  - Aggregation of Silver Hydrosols Prepared in Air.
AB  - The chemistry involved in the preparation and activation of silver hydrosols was
      monitored by pH, potential, and surface charge measurements, by absorption
      spectra in the visible region, and by surface-enhanced Raman spectroscopy (SERS).
      The activation, displayed by a red-shift of the colloid absorption at 392 nm,
      corresponds to a partial aggregation of elementary silver particles as displayed
      by transmission electron micrographs. The participation of carbonate species in
      the chemistry of hydrosols handled in air was made obvious by titration with
      strong acids. The colloid destabilization was performed either with protons, by
      adding strong non-complexing acids (HNO3, HClO4), or with low concentrations of
      Cu2+. In contrast, HCl determined a stabilization of hydrosols related to the
      complexing affinity of Cl- toward silver. The successive addition of Cu(NO3)2 and
      HCl allowed a balance between all the chemical reactions and a very efficient
      activation process. Whereas the chemical reactants used are nominally inorganic,
      at total concentrations lower than 10(-3) M, the activated hydrosols display
      anomalous SER spectra which were previously assigned to organic molecules.
      Copyright 1998 Academic Press.

PMID- 9761653
TI  - Dispersion Properties of Silicon Nitride Powder Coated with Yttrium and Aluminium
      Precursors.
AB  - A coated silicon nitride (Si3N4) powder with yttria and alumina precursors as
      sintering additives was prepared by a heterogeneous precipitation method. The
      rheological and electrophoretic properties of the suspensions obtained from the
      coated (CO) powder were investigated and compared with those of pure Si3N4 powder
      and of the mechanically mixed (MM) powders of Al2O3, Si3N4, and Y2O3. The results
      showed that the CO powder calcined at 500 degreesC exhibited improved dispersion
      properties compared with the pure Si3N4 powders. The CO powder possessed the
      surface character of Al2O3 and Y2O3 particles, that made it easier to process in
      aqueous media, yielding a higher solid loading than the pure Si3N4 powder. These
      improvements were attributed to a change in the resultant interaction forces
      between particles from attractive (pure Si3N4, and MM powders) to repulsive in
      the case of the CO powder. A homogeneous distribution of sintering additives in
      the Si3N4 matrix was obtained. Copyright 1998 Academic Press.

PMID- 9761654
TI  - Covalent Grafting of Phenylphosphonate Groups onto the Interlamellar Aluminol
      Surface of Kaolinite.
AB  - Kaolinite (K) was reacted with phenylphosphonic acid (PPA) in a water:acetone
      (1:1 V/V) solution (molar ratio 1 K:3 PPA), at 95 +/- 5 degreesC for different
      periods of time. Two different compounds (white powders) were identified but only
      one was isolated as a single phase and characterized by X-ray diffraction (powder
      method), thermal analysis (TG-DSC), Fourier-transformed infrared spectroscopy,
      and chemical analysis. The first compound showed a layer expansion of 7.86 A and
      the second, a layer expansion of 9.29 A, obtained as a decomposition product.
      Both compounds are consistent with the grafting of the phenylphosphonate group to
      the layers of kaolinite. The compounds have a formula of Al2Si2O5(OH)(HO3PPh)3.0
      . 2H2O, as determined by thermal (water and total organic matter loss) and
      chemical (C content) analysis, respectively. Copyright 1998 Academic Press.

PMID- 9761655
TI  - Measurements of Contact Angles between an Oil-Water Interface and a Fiber by the
      ACDPAC Technique.
AB  - The ACRPAC (Analysis of Capillary Rise Profile Around a Cylinder) method was
      modified and extended to measure the contact angles between an oil-water
      interface and a fiber. Basically, the accurate image of the partial capillary
      depression profile was acquired and digitized by applying computer digital image
      processing and analysis techniques. The contact angle was determined by finding
      the best fit of the theoretically predicted profile, i.e., the curve representing
      a solution of the Laplace equation of capillarity, to the physically observed
      liquid-liquid interface. This analysis of the capillary depression profile around
      a cylinder (ACDPAC) technique was used to measure the contact angles of different
      water-oil interfaces on cylindrical glass fibers pre-coated with FC725. The
      wettability of the fiber-water-oil systems with varying oil and aqueous phases
      was examined. In particular, the wetting effects of a cationic surfactant
      cetyltrimethylammonium bromide (CTAB) and an anionic surfactant sodium dodecyl
      sulfate (SDS) dissolved in the aqueous phase were studied by using the ACDPAC
      technique. The oil phases tested were two dimethyl siloxane liquids, silicone oil
      A-type and silicone oil B-type. Copyright 1998 Academic Press.

PMID- 9761656
TI  - Biosorption of Heavy Metal Ions to Brown Algae, Macrocystis pyrifera,
      Kjellmaniella crassiforia, and Undaria pinnatifida.
AB  - A fundamental study of the application of brown algae to the aqueous-phase
      separation of toxic heavy metals was carried out. The biosorption characteristics
      of cadmium and lead ions were determined with brown algae, Macrocystis pyrifera,
      Kjellmaniella crassiforia, and Undaria pinnatifida. A metal binding model
      proposed by the authors was used for the description of metal binding data. The
      results showed that the biosorption of bivalent metal ions to brown algae was due
      to bivalent binding to carboxylic groups on alginic acid in brown algae.
      Copyright 1998 Academic Press.

PMID- 9761657
TI  - Colloidal Particles at Water-Glass Interface: Analyzing Videomicroscopic Data.
AB  - Direct videomicroscopic observations provide a powerful tool for investigations
      on the deposition of colloidal particles at liquid-solid interfaces. However, the
      technique is also capable of producing artefacts caused mainly by limited
      resolution. In the present contribution we discuss the possibilities and
      limitations of videomicroscopic observations, focussing thereby on an application
      example, namely particle deposition from flow in a parallel plate channel in the
      presence of a repulsive barrier. We outline algorithms for the determination of
      the relevant quantities, indicate the pitfalls, and provide correction formulas.
      Special attention is paid to the kinetics of particle release, namely to the
      accurate determination of the distribution of the times the particles spend
      adhering to the surface. In our example the kinetics of the release is found to
      be highly nonexponential, but an adequate fit of the measured distribution of
      adhesion times is obtained with a stretched exponential exp[-(betatau)nu], where
      nu approximately 0.5 and beta approximately 3 x 10(-5) s-1. Copyright 1998
      Academic Press.

PMID- 9761658
TI  - Colloidal Particles at Water-Glass Interface: Deposition Kinetics and Surface
      Heterogeneity.
AB  - Videomicroscopy in combination with evanescent field illumination is applied to
      study the sorption of colloidal particles from flow in a parallel plate channel
      on a glass surface. The experiments, carried out in the presence of a repulsive
      electrostatic barrier, reveal surprisingly complex results: The glass surface,
      though optically flat and well cleaned, is not homogeneous, but rather the
      sorption occurs at a limited number of preferred sites. Moreover, these sites are
      not static: new sites keep appearing at random positions on the observed surface
      and disappearing at a rate of kd = 1.3 x 10(-5) s-1. These findings can be
      understood within a simple model that takes into account slow but inevitable
      dissolution of the glass surface. The bulk glass contains potential adsorbers,
      which are continuously being exposed by the dissolution process and act as
      transient adsorption sites, before being washed off by the flowing buffer
      solution. Copyright 1998 Academic Press.

PMID- 9761659
TI  - Colloidal Particles at Solid-Liquid Interfaces: Mechanisms of Desorption
      Kinetics.
AB  - We study the sorption of colloids on equally charged surfaces. Our focus is on
      the time scale from hours to weeks, where adsorption is not an irreversible
      process but interplays with (spontaneous) desorption. Using model calculations,
      we show how the desorption kinetics is influenced by readsorption, a potential
      barrier, a secondary potential minimum, local variation of the potential, and
      bond aging. In the experimental part we present results of in situ observation of
      the sorption kinetics of polystyrene latex particles onto a glass surface.
      Combining the evanescent field method with video microscopy, we were able to
      identify the particle arrival and departure times individually and therefrom
      determine the adhesion time distribution function. The nonexponentiality of this
      function can be explained by a gamma distribution of the potential depth at the
      binding sites as well as by logarithmic bond aging. Copyright 1998 Academic
      Press.

PMID- 9761660
TI  - Experimental Evidence of the Effect of Evaporation-Condensation on Thermal
      Marangoni Flows in Aqueous Fatty Alcohol Solutions.
AB  - The static surface tension (final sigmae) of aqueous solutions of a fatty alcohol
      versus temperature exhibits a minimum. Thus, a temperature gradient which is
      created at the free surface of such a solution at temperatures higher than that
      of the minimum (final sigmae) should induce a surface flow from the cold area to
      the hot one. This was indeed observed even at temperatures much lower than that
      of the minimum. A possible explanation is the evaporation of alcohol at the hot
      area where the surface tension increases, and its condensation on the cold area
      where the surface tension decreases, the alcohol being tranported by the gas
      phase. The thickness of the gas phase over the liquid could play a role in the
      observed flows. A device was built in which the thickness of the gas phase could
      be adjusted. Experiments performed with a 6.2 x 10(-3) m solution of n-heptanol
      indicate a lowering of the surface velocity where the thickness of the gas phase
      is reduced. Copyright 1998 Academic Press.

PMID- 9761661
TI  - The Influence of a Dynamic Stern Layer on the Primary Electroviscous Effect.
AB  - The theory developed by Watterson and White (Watterson, I. G., and White, L. R.,
      J. Chem. Soc., Faraday Trans. 2 77, 1115 (1981)) to calculate the primary
      electroviscous coefficient of a suspension of charged spherical colloidal
      particles has been extended, by considering the presence of a dynamic Stern layer
      onto the particle surface, following the method developed by Mangelsdorf and
      White (Mangelsdorf, C. S., and White, L. R., J. Chem. Soc. Faraday Trans. 80,
      2859 (1990)) for electrophoresis. The presence of mobile ions causes the primary
      electroviscous coefficient to decrease compared to when the Stern layer ions are
      inmobile. A separate dependence of the primary electroviscous coefficient on
      kappa-1 (Debye length) and a (particle radius) has been found. Copyright 1998
      Academic Press.

PMID- 9761662
TI  - Dehydration of Hydrated Bilayer of Dipalmitoylphosphatidylcholine Caused by
      Beryllium Ion: Evidence from a Differential Scanning Calorimetry of Bilayer Phase
      Transition.
AB  - The effect of polyvalent metal ions Be2+, Mg2+, Ca2+, Sr2+, Ba2+, and La3+ on the
      phase transition behavior of hydrated bilayer of dipalmitoylphosphatidylcholine
      (DPPC) was investigated by differential scanning calorimetry (DSC) in relation to
      their ability to induce the aggregation of DPPC vesicles. The addition of the
      metal ions other than Be2+ provided DSC thermograms characteristic to a fully
      hydrated DPPC bilayer. By the addition of Be2+, the endothermic peak associated
      with the bilayer phase transition was shifted to that corresponding to partially
      dehydrated DPPC bilayer, which was reported by Kodama et al. (Biochem. Biophys.
      Acta 689, 567, 1982). This demonstrates that Be2+ causes dehydration of DPPC head
      group in hydrated bilayer and supports the speculation that the unusual property
      of Be2+ to induce the aggregation of PC vesicles is attributed to the destruction
      of repulsive hydration force due to the partial dehydration of vesicular surface.
      Copyright 1998 Academic Press.

PMID- 9761663
TI  - The Effect of Polar Head Charge Delocalization on Micellar Aggregation Numbers of
      Decylpyridinium Salts, Revisited.
AB  - The distribution of charge in an isomeric series of decylpyridinium bromide
      surfactants is calculated using the AM1 semiempirical quantum mechanical
      molecular model. The aggregation numbers of the surfactants are shown to increase
      with a decrease in the residual partial charge in the alkyl tails, suggesting a
      change in the packing of the surfactants. The critical micelle concentration
      increases with a decrease in the partial charge of the head groups, indicating
      increased solubility of the surfactant molecule as charge is more widely
      distributed throughout the molecule. Copyright 1998 Academic Press.

PMID- 9761664
TI  - The zeta-Potential of Silicone Oil Droplets Dispersed in Aqueous Solutions.
AB  - An experimental method to measure the zeta-potential of small liquid droplets
      dispersed in another immiscible liquid was presented in this paper. Basically, a
      liquid droplet was held stationary in a test cell by applying a proper static
      electric field. An existing theory shows that the electrical force experienced by
      the droplet can be related to the zeta-potential of the liquid droplet. Thus the
      zeta-potential can be determined from the force balance among the electrical
      force, the gravitational force, and the buoyancy force being exerted on the
      stationary droplet. This electrical suspension method was applied to study the
      effects of pH values, ionic features, and concentrations of three electrolytes
      and two ionic surfactants on the zeta-potential of the silicone oil (No. 1)
      droplets. Copyright 1998 Academic Press.

PMID- 9761665
TI  - Characterization of Concentrated Magnetic Colloids by Measurements of Frequency
      Dependence of AC Magnetic Susceptibility.
AB  - The AC magnetic susceptibility frequency dependence in the range 10 Hz-10 kHz is
      used to study concentrated magnetic colloids. Different theoretical and empirical
      models are used to describe the frequency dependence. The magnetic analogue of
      the Cole-Cole model is found to be most suitable. Values of the model fitting
      parameters and the relaxation time distribution provide information about the
      dispersability, viscoelastic properties, and interparticle interactions in the
      magnetic colloids. Copyright 1998 Academic Press.

PMID- 9761666
TI  - Effective Charge on Polymer Colloids Obtained Using a Renormalization Model.
AB  - Static light scattering has been used to study the electrostatic interaction
      between colloidal particles. Experiments were carried out using a latex with a
      very small diameter, allowing structure determination at high particle
      concentration. The obtained effective charge characterizing this interaction is
      found to be smaller than the bare charge determined from titration. A
      renormalization model connecting both values has been used. The agreement between
      the renormalized charge and that obtained from scattering data seems to point out
      that this model operates well. Copyright 1998 Academic Press.

PMID- 9761667
TI  - 13C-NMR Evidence on Amphiphile Lifetime in Reverse (Water-in-Oil) Micelles Formed
      by a Poloxamer Block Copolymer.
AB  - The dynamics of exchange between amphiphile assembled in reverse (water-in-oil)
      micelles and unimer (free in solution) amphiphile were probed by 13C-NMR
      spectroscopy in a ternary isothermal system consisting of a poly(ethylene oxide)
      poly(propylene oxide) block copolymer (poloxamer), water, and xylene. An upper
      bound was obtained for the lifetime of a block copolymer molecule within the
      reverse micelle, using the theoretical treatment of exchange phenomena in NMR
      which is based on extensions of the Bloch equations. Copyright 1998 Academic
      Press.

PMID- 9761668
TI  - Telomeric interactions result in the formation of intramolecular circles behaving
      as topologically constrained.
AB  - The gene-sized macronuclear DNA molecules of hypotrichous ciliates carry
      telomeric sequences of homogenous length. Incubation of these molecules at low
      concentrations in the presence of monovalent cations (K+, Na+, Cs+) leads to the
      formation of intramolecular circles. They can be visualized on one or two
      dimensional agarose gels only when KCl is present in the gel. From their
      electrophoretic behavior on agarose gels as well as on density gradients it can
      be concluded that they are topologically constrained. Digestion of macronuclear
      DNA with S1 as well as various exonucleases indicate that both the 3' overhang
      and the 5' C-rich strand of the telomeric repeat is involved in these
      interactions. Several models of these interactions are discussed.

PMID- 9761669
TI  - Implications for function and therapy of a 2.9 A structure of binary-complexed
      antithrombin.
AB  - The crystal structure of a binary complex of human antithrombin with a peptide of
      the same sequence as its reactive loop (P14-P3) has been determined at 2.9 A. The
      peptide binds as the middle strand s4A in the A beta-sheet, homologously to that
      of the reactive loop in the latent and cleaved forms of antithrombin. Peptide
      binding results in the complete expulsion of the hinge region of the loop from
      the A beta-sheet although the conformation differs from that of heparin-activated
      antithrombin. The 36-fold increase in the rate of reaction of the binary complex
      with factor Xa indicates that full loop expulsion alone is not sufficient for
      complete heparin activation of antithrombin but that this is also dependent on
      the overall conformation of the molecule. Previous studies have demonstrated that
      reactive loop peptides can block or reverse the polymerisation of serpins
      associated with cirrhosis and thrombosis. The antithrombin binary complex
      structure defines the precise localisation of the blocking peptide in a serpin
      and provides the basis for rational drug design for mimetics that will prevent
      polymerisation in vivo and so ameliorate the associated disease.

PMID- 9761670
TI  - Regulation of the Caenorhabditis elegans gut cysteine protease gene cpr-1:
      requirement for GATA motifs.
AB  - Expression of the Caenorhabditis elegans cysteine protease gene cpr-1 is
      regulated both spatially and temporally. In situ hybridisation and Northern blot
      analysis have shown that this gene is expressed exclusively in gut cells of all
      developmental stages except the embryo. We now show by transgenic transformation
      with cpr-1/lac Z reporter gene constructs that a sequence contained within the
      cpr-1 5' flanking region can direct this spatial and temporal expression.
      Deletion analysis of the cpr-1 promoter indicates that as little as 212 bp of
      upstream sequence is sufficient for this expression, although more upstream
      sequence may be involved in quantitative regulation of expression. Mutation of
      two GATA-like sequence elements at positions -51 and -147 upstream of the
      transcription start site ablates all expression, indicating an essential role in
      cpr-1 regulation. A concatemer of the cpr-1 -147 GATA motif placed upstream of
      minimal promoter/lac Z reporter gene constructs results in strong reporter gene
      expression in gut cells of larval stages and also in embryos. Weak expression is
      also detected in hypodermal cells. This pattern is reversed in the adult stage
      with strong expression in hypodermal cells and weaker expression in gut cells.
      Our findings suggest that spatial and temporal regulation of the cpr-1 gene is
      complex and involves activation by a GATA-like transcription factor.

PMID- 9761671
TI  - Multiple oligomerisation domains in the IS911 transposase: a leucine zipper motif
      is essential for activity.
AB  - Structure-function relationships involved in oligomerisation of the transposase
      OrfAB of the bacterial insertion sequence IS911 have been investigated. Site
      directed mutagenesis and sequential deletion coupled with immunoprecipitation
      have led to the definition of three regions of the protein capable of promoting
      multimerisation. These include a region predicted to assume a coiled-coil
      conformation, which is shown to be essential for activity, promoting correct
      multimerisation of the N-terminal domain of OrfAB and sequence-specific binding
      to the IS911 terminal inverted repeats mediated by this domain. This region
      presents the structural and functional characteristics of the leucine zipper
      motif described in eukaryotic proteins. The two other regions are located further
      towards the C-terminal end of the protein, adjacent to the leucine zipper and in
      the region that carries the conserved catalytic DD(35)E motif.

PMID- 9761672
TI  - Sequence-dependent extrusion of a small DNA hairpin at the N4 virion RNA
      polymerase promoters.
AB  - Bacteriophage N4 virion RNA polymerase promoters contain five to seven-base
      inverted repeats separated by three bases and centered at position -12 from the
      site of transcription initiation. We have previously shown that these inverted
      repeats extrude as hairpins at physiological superhelical densities in a Mg(II)
      dependent manner. Mg(II)-dependent hairpin extrusion at promoters P1 and P2
      displays quantitative differences in reactivity to structural probes at different
      DNA superhelical densities, with extrusion at P2 being more favored at low
      superhelical density. Analyses of mutant promoters using structure-specific
      probes revealed that specific sequences, at the closing base-pair of the hairpin
      and at the loop (i.e. 5'-C-GXA-G-3' where X=G, A, T), are required for extrusion
      of the small promoter hairpins at physiological superhelical density. The
      sequence-dependent requirements for extrusion of the small N4 promoter hairpins
      may be generally applicable for other such sequences found both in prokaryotic
      and eukaryotic genomes.

PMID- 9761673
TI  - Towards the design of rare cutting restriction endonucleases: using directed
      evolution to generate variants of EcoRV differing in their substrate specificity
      by two orders of magnitude.
AB  - The restriction endonuclease EcoRV cleaves DNA highly specifically within GATATC
      sequences. In order to create EcoRV variants that have an extended recognition
      site we have employed a semi-rational random mutagenesis/selection procedure.
      Twenty-two amino acid residues were subjected to random mutagenesis and about 500
      EcoRV variants representing three generations of mutants were screened. Among
      these some highly active variants that strongly prefer AT-flanked cleavage sites
      (e.g. S183A/Q224R, T93S/I103F/S183A/T222S or N97T/S183A/T222S) and others that
      prefer GC flanks (e.g. K104N/A181T) were identified. As wild-type EcoRV does not
      discriminate between these cleavage sites, the generation of these variants
      represents a significant first step towards redesigning EcoRV to become an 8 or
      10 bp cutter. Such enzymes, only very rarely found in nature, could be extremely
      helpful for the manipulation of large DNA fragments.

PMID- 9761674
TI  - The first step: activation of the Semliki Forest virus spike protein precursor
      causes a localized conformational change in the trimeric spike.
AB  - The structure of the particle formed by the SFVmSQL mutant of Semliki Forest
      virus (SFV) has been defined by cryo-electron microscopy and image reconstruction
      to a resolution of 21 A. The SQL mutation blocks the cleavage of p62, the
      precursor of the spike proteins E2 and E3, which normally occurs in the trans
      Golgi. The uncleaved spike protein is insensitive to the low pH treatment that
      triggers membrane fusion during entry of the wild-type virus. The conformation of
      the spike in the SFVmSQL particle should correspond to that of the inactive
      precursor found in the early stages of the secretory pathway. Comparison of this
      "precursor" structure with that of the mature, wild-type, virus allows
      visualization of the changes that lead to activation, the first step in the
      pathway toward fusion. We find that the conformational change in the spike is
      dramatic but localized. The projecting domains of the spikes are completely
      separated in the precursor and close to generate a cavity in the mature spike.
      E1, the fusion peptide-bearing protein, interacts only with the p62 in its own
      third of the trimer before cleavage and then collapses to form a trimer of
      heterotrimers (E1E2E3)3 surrounding the cavity, poised for the pH-induced
      conformational change that leads to fusion. The capsid, transmembrane regions and
      the spike skirts (thin layers of protein that link spikes above the membrane)
      remain unchanged by cleavage. Similarly, the interactions of the spikes with the
      nucleocapsid through the transmembrane domains remain constant. Hence, the
      interactions that lead to virus assembly are unaffected by the SFVmSQL mutation.

PMID- 9761675
TI  - Surface analysis of the photosystem I complex by electron and atomic force
      microscopy.
AB  - Two-dimensional (2D) crystals of the photosystem I (PSI) reaction center from
      Synechococcus sp. OD24 were analyzed by electron and atomic force microscopy.
      Surface relief reconstructions from electron micrographs of freeze-dried
      unidirectionally shadowed samples and topographs recorded with the atomic force
      microscope (AFM) provided a precise definition of the lumenal and stromal PSI
      surfaces. The lumenal surface was composed of four protrusions that surrounded an
      indentation. One of the protrusions, the PsaF subunit, was often missing. Removal
      of the extrinsic proteins with the AFM stylus exposed the stromal side of the PSI
      core, whose surface structure could then be imaged at a resolution better than
      1.4 nm. This interfacial surface between core and extrinsic subunits, had a
      pseudo-2-fold symmetry and protrusions that correlated with the surface helices e
      and e' or were at the sites of putative alpha-helix-connecting loops estimated
      from the 4 A map of the complex. The molecular dissection achieved with the AFM,
      opens new possibilities to unveil the interfaces between subunits of
      supramolecular assemblies.

PMID- 9761676
TI  - The nature of antibody heavy chain residue H6 strongly influences the stability
      of a VH domain lacking the disulfide bridge.
AB  - Monoclonal antibody mAb 03/01/01, directed against the musk odorant traseolide,
      carries a serine residue instead of the conserved Cys H92 in the heavy chain
      variable domain, and is thus lacking the highly conserved disulfide bridge. We
      investigated the energetic consequence of restoring the disulfide bond and the
      nature of residue H6 (Glu or Gln), which is poised to interact with Ser H92 in
      the recombinant scFv fragment obtained from this antibody. In the scFv fragment
      derived from this antibody, the stabilizing effect of Gln H6 over Glu was found
      to be as large as the effect of reintroducing the disulfide bond. We have
      analyzed the conformation and hydrogen bond pattern of Gln H6 and Glu H6 in
      antibodies carrying these residues and suggest mechanisms by which this residue
      could contribute to VH domain stability. We also show that the unpaired cysteine
      H22 is buried, and conforms to the expected VH structure. The antibody appears to
      have acquired two somatic mutations (Ser H52 and Arg H66), which had been
      previously characterized as having a positive effect on VH stability. The overall
      domain stability is the decisive factor for generating functional, disulfide-free
      antibody domains, and several key residues play dominant roles.

PMID- 9761677
TI  - Fragile X DNA triplet repeats, (GCC)n, form hairpins with single hydrogen-bonded
      cytosine.cytosine mispairs at the CpG sites: isotope-edited nuclear magnetic
      resonance spectroscopy on (GCC)n with selective 15N4-labeled cytosine bases.
AB  - Here, we provide a direct proof that the formation of hairpins by (GCC)n at the
      5'-UTR of the FMR-1 gene offers a mechanism for CpG hypermethylation associated
      with the fragile X syndrome. For this, we have performed hetero-nuclear (15N-1H)
      magnetic resonance spectroscopy to probe the structure of the CpG sites in the
      (GCC)n hairpins that are 15N-labeled at the amino (N4) groups of specific
      cytosine bases. Analyses of chemical shift, pH-induced chemical exchange, and NOE
      pattern of the (15N-labeled) amino protons of cytosine bases reveal that the
      cytosine bases at the CpG sites are intrahelical and well-stacked with the
      neighboring G.C base-pairs in the stem of these hairpins and probably form single
      hydrogen-bonded C.C mispairs. Measurements of pH-dependent 1H line-width also
      demonstrate that the C.C mispairs are more susceptible to open-closure than the
      G.C base-pairs. Thus, the Cs at the CpG sites of the (GCC)n hairpin are "flipped
      out" more easily to the activated state than those in the corresponding Watson
      Crick duplex, (GCC)n. (GGC)n and this makes the hairpin a better target for
      methylation by the human methyltransferase, the enzyme that methylates the Cs at
      the CpG sites.

PMID- 9761678
TI  - Three-dimensional structure of O-acetylserine sulfhydrylase from Salmonella
      typhimurium.
AB  - The last step in cysteine biosynthesis in enteric bacteria is catalyzed by the
      pyridoxal 5'-phosphate-dependent enzyme O-acetylserine sulfhydrylase. Here we
      report the crystal structure at 2.2 A resolution of the A-isozyme of O
      acetylserine sulfhydrylase isolated from Salmonella typhimurium. O-acetylserine
      sulfhydrylase shares the same fold with tryptophan synthase-beta from Salmonella
      typhimurium but the sequence identity level is below 20%. There are some major
      structural differences: the loops providing the interface to the alpha-subunit in
      tryptophan synthase-beta and two surface helices of tryptophan synthase-beta are
      missing in O-acetylserine sulfhydrylase. The hydrophobic channel for indole
      transport from the alpha to the beta active site of tryptophan synthase-beta is,
      not unexpectedly, also absent in O-acetylserine sulfhydrylase. The dimer
      interface, on the other hand, is more or less conserved in the two enzymes. The
      active site cleft of O-acetylserine sulfhydrylase is wider and therefore more
      exposed to the solvent. A possible binding site for the substrate O-acetylserine
      is discussed.

PMID- 9761679
TI  - Catalytic competence of O-acetylserine sulfhydrylase in the crystal probed by
      polarized absorption microspectrophotometry.
AB  - The reactions of the pyridoxal 5'-phosphate-dependent enzyme O-acetylserine
      sulfhydrylase with the substrate O-acetyl-L-serine and substrate analogs have
      been investigated in the crystalline state by single-crystal polarized absorption
      microspectrophotometry. This approach has allowed us to examine the catalytic
      competence of the enzyme in different crystalline states, one of which was used
      to determine the three-dimensional structure; experimental conditions were
      defined for the accumulation of catalytic intermediates in the crystal suitable
      for crystallographic analyses.O-Acetyl-L-serine reacts with the enzyme in one of
      the crystal forms leading via a beta-elimination reaction to the accumulation of
      the alpha-aminoacrylate Schiff base, absorbing maximally at 320 and 470 nm, as in
      solution. The dissociation constant for the alpha-aminoacrylate Schiff base is in
      the millimolar range, 500-fold higher than in solution, suggesting that crystal
      lattice interactions may oppose functionally relevant conformational changes. The
      dissociation constant exhibits a bell-shaped dependence on pH centered at pH 7.
      At this pH the alpha-aminoacrylate species slowly decays with time (30% decrease
      in 24 hours). The alpha-aminoacrylate intermediate readily reacts with sodium
      azide, an analog of sulfide, the natural nucleophilic agent, to give a new amino
      acid and the native enzyme, indicating that the crystalline enzyme catalyzes the
      overall beta-replacement reaction as in solution. In other crystal forms,
      including that used for the X-ray investigation, O-acetyl-L-serine either has an
      even higher dissociation constant or causes crystal damage upon binding. When the
      crystalline enzyme reacts with either L-cysteine or L-serine, the external
      aldimine intermediate is formed. The dissociation constants for both substrate
      analogs are closer to those observed in solution and are modulated by pH as in
      solution. Findings demonstrate that O-acetylserine sulfhydrylase is catalytically
      competent in the crystal although some regions of the molecule, likely involved
      in an open-closed transition induced by O-acetyl-L-serine binding, may have a
      limited flexibility. The accumulation in the crystal of both the external
      aldimine and the alpha-aminoacrylate intermediate makes feasible their structural
      determination and, therefore, the elucidation of the catalytic pathway at the
      molecular level.

PMID- 9761680
TI  - Unexpected binding mode of tick anticoagulant peptide complexed to bovine factor
      Xa.
AB  - The structure of recombinant tick anticoagulant peptide (rTAP) complexed to
      bovine factor Xa at 3.0 A resolution reveals the structural basis for the
      specificity and the high affinity of rTAP. Three N-terminal residues, Tyr501,
      Asn502 and Arg503, play a critical role in the complex formation as suggested by
      earlier mutagenic studies and the ornithodorin-thrombin complex. Unexpectedly,
      the side-chain of Tyr501 is located in the S1 pocket, although factor Xa favors
      arginine as a P1 residue. Arg503 is located at the aryl binding pocket and forms
      a salt-bridge with Glu97 of factor Xa. The autolysis loop, which is disordered in
      the uninhibited factor Xa structure, is involved in the formation of the complex
      as a part of the secondary binding site. The C-terminal helix of rTAP interacts
      with factor Xa as a secondary binding determinant. The N-terminal residues of
      rTAP reorganize during the formation of the factor Xa-rTAP complex from the
      conformation found in the solution into an extended conformation. The presence of
      the secondary binding site confirms the proposed two-step kinetic mechanism based
      on the results of a mutagenesis study.

PMID- 9761681
TI  - Structure of the capsid of Pf3 filamentous phage determined from X-ray fibre
      diffraction data at 3.1 A resolution.
AB  - We have recorded X-ray diffraction patterns at 3.1 A resolution from magnetically
      aligned fibres of the Pf3 strain of filamentous bacteriophage (Inovirus). The
      patterns are similar to patterns from the higher-temperature form of the Pf1
      strain, indicating that the Pf3 and Pf1 virions have the same helix symmetry and
      similar protein subunit shape. This is of particular interest, given that the
      primary structures of the two protein subunits are quite different; and the
      nucleotide/protein subunit ratio in the Pf3 virion is more than twice that in
      Pf1, indicating important differences in DNA packaging. We have built a molecular
      model of the Pf3 protein capsid based on the model of Pf1, and refined it against
      the diffraction data using simulated annealing. The refinement confirms that the
      two structures are similar, which may reflect a fundamental motif of alpha-helix
      packing. However, there are some differences between the structures: the Pf3
      subunit appears to be completely alpha-helical, beginning at the N terminus,
      whereas the first few residues of the Pf1 subunit are not helical; and the
      structure of the C-terminal region of the Pf3 subunit at the inner surface of the
      tubular capsid indicates that DNA/protein interactions in this virion may involve
      both aromatic side-chains and positively charged side-chains, whereas those in
      the Pf1 virion involve predominantly only the latter. In the course of this work,
      we have developed new approaches to refinement and validation of helical
      structures with respect to continuous transform fibre diffraction data.

PMID- 9761682
TI  - Three-dimensional structure of H-2Dd complexed with an immunodominant peptide
      from human immunodeficiency virus envelope glycoprotein 120.
AB  - The crystal structure of the mouse major histocompatibility complex (MHC) class I
      molecule H-2Dd with an immunodominant peptide, designated P18-I10 (RGPGRAFVTI),
      from human immunodeficiency virus envelope glycoprotein 120 was determined at 3.2
      A resolution. A novel orientation of the alpha3 domain of Dd relative to the
      alpha1/alpha2 domains results in significantly fewer contacts between alpha3 and
      beta2-microglobulin compared with other MHC class I proteins. Four out of ten
      peptide residues (P2 Gly, P3 Pro, P5 Arg and P10 Ile) are nearly completely
      buried in the Dd binding groove. This is consistent with previous findings that
      Dd exploits a four-residue binding motif comprising a glycine at P2, a proline at
      P3, a positively charged residue at P5, and a C-terminal hydrophobic residue at
      P9 or P10. The side-chain of P5 Arg is directed toward the floor of the
      predominantly hydrophobic binding groove where it forms two salt bridges and one
      hydrogen bond with Dd residue Asp77. The selection of glycine at P2 appears to be
      due to a narrowing of the B pocket, relative to that of other class I molecules,
      caused by Arg66 whose side-chain folds down into the binding cleft. Residue P3
      Pro of P18-I10 occupies part of pocket D, which in Dd is partially split by a
      prominent hydrophobic ridge in the floor of the binding groove formed by Trp97
      and Trp114. Residues P6 through P9 form a solvent-exposed bulge, with P7 Phe
      protruding the most from the binding groove and thereby probably constituting a
      major site of interaction with T cell receptors. A comparison of H-2Dd/P18-I10
      with other MHC class I/peptide complexes of known structure provides insights
      into the possible basis for the specificity of the natural killer cell receptor
      Ly-49A for several related class I molecules.

PMID- 9761683
TI  - Differences in the intersubunit contacts in triosephosphate isomerase from two
      closely related pathogenic trypanosomes.
AB  - The aligned amino acid sequences of TIM from Trypanosoma cruzi (TcTIM) and
      Trypanosoma brucei (TbTIM) have a positional identity of 68%. The two enzymes
      have markedly similar catalytic properties. Agents that interact with their
      interface Cys inhibit TcTIM and TbTIM; and those TIMs that lack this Cys (such as
      human TIM) are largely or completely insensitive to these agents. The
      susceptibility of TcTIM to the agents is approximately 100 times higher than that
      of TbTIM. To ascertain the cause of this large difference, the crystal structure
      of TcTIM was solved at 1.83 A resolution. The two enzymes are very similar
      homodimers. In TcTIM and TbTIM their respective Cys, 15 or 14, forms part of the
      dimer interface. In both, the contacts of the Cys with residues of the other
      subunit are almost identical. Nevertheless, there are noteworthy differences
      between the two; the existence of glutamine 18 in TbTIM instead of glutamic acid
      in TcTIM at the beginning of helix 1 decreases the contacts between this portion
      of the protein and helix 3 of the other subunit. In addition, TcTIM has proline
      at position 24 in the first helix of the TIM barrel; this is absent in the other
      TIM. Pro24 disrupts the regular helix arrangement, making the pitch of this helix
      1.2 A longer than in TbTIM. When Pro24 of TcTIM was substituted for Glu, the
      sensitivity of TcTIM to sulfhydryl reagents increased about fivefold, possibly as
      a consequence of an increase in the space between the first portion of helix 1
      and helix 3 of the other subunit. Therefore, it may be concluded that the
      geometry of the latter region is central in the accessibility to agents that
      perturb the interface Cys. In human TIM this region is more compact.

PMID- 9761684
TI  - A structural homologue of colipase in black mamba venom revealed by NMR floating
      disulphide bridge analysis.
AB  - The solution structure of mamba intestinal toxin 1 (MIT1), isolated from
      Dendroaspis polylepis polylepis venom, has been determined. This molecule is a
      cysteine-rich polypeptide exhibiting no recognised family membership. Resistance
      to MIT1 to classical specific endoproteases produced contradictory NMR and
      biochemical information concerning disulphide-bridge topology. We have used
      distance restraints allowing ambiguous partners between S atoms in combination
      with NMR-derived structural information, to correctly determine the disulphide
      bridge topology. The resultant solution structure of MIT1, determined to a
      resolution of 0.5 A, reveals an unexpectedly similar global fold with respect to
      colipase, a protein involved in fatty acid digestion. Colipase exhibits an
      analogous resistance to endoprotease activity, indicating for the first time the
      possible topological origins of this biochemical property. The biochemical and
      structural homology permitted us to propose a mechanically related digestive
      function for MIT1 and provides novel information concerning snake venom protein
      evolution.

PMID- 9761685
TI  - Backbone dynamics of the CDK inhibitor p19(INK4d) studied by 15N NMR relaxation
      experiments at two field strengths.
AB  - The four members of the INK4 gene family, p16(INK4a), p15(INK4b), p18(INK4c) and
      p19(INK4d), are known to bind to and inhibit the closely related cyclin-dependent
      kinases CDK4 and CDK6 as part of the regulation of the G1/S transition in the
      cell division cycle. Loss of INK4 gene product function, and particularly that of
      p16(INK4a), is found in human cancer. 15N NMR relaxation rates of p19(INK4d) were
      analyzed using the reduced spectral density mapping method. Most of the backbone
      of p19(INK4d) exists in a well-defined structure of limited conformational
      flexibility on the nanosecond to picosecond time-scales. Introducing appropriate
      scaling to account for the effects of anisotropy, a considerable amount of
      exchange broadening was found for several residues throughout the sequence,
      especially residues in the second ankyrin repeat and in the beginnings and ends
      of loops connecting ankyrin repeats. A possible mode of binding between
      p19(INK4d) and CDK4 and CDK6 could therefore involve the loop segments of
      p19(INK4d). The average overall correlation time taumeff was determined to be
      13.6 ns, reflecting the tendency of p19(INK4d) to aggregate.

PMID- 9761686
TI  - The solution structure of a cytotoxic ribonuclease from the oocytes of Rana
      catesbeiana (bullfrog).
AB  - RC-RNase is a pyrimidine-guanine sequence-specific ribonuclease and a lectin
      possessing potent cell cytotoxicity. It was isolated from the oocytes of Rana
      catesbeiana (bull frog). From analysis of an extensive set of 1H homonuclear 2D
      NMR spectra we have completed the resonance assignments. Determination of the
      three-dimensional structure was carried out with the program X-PLOR using a total
      of 951 restraints including 814 NMR-derived distances, 61 torsion angles, and 76
      hydrogen bond restraints. In the resultant family of 15 best structures, selected
      from a total of 150 calculated structures, the root-mean-square deviation from
      the average structure for the backbone heavy-atoms involved in well-defined
      secondary structure is 0.48 A, while that for all backbone heavy-atoms is 0.91 A.
      The structure of RC-RNase consists of three alpha-helices and two triple-stranded
      anti-parallel beta-sheets and folds in a kidney-shape, very similar to the X-ray
      crystal structure of a homolo gous protein, onconase isolated from Rana pipiens.
      We have also investigated the interaction between RC-RNase and two inhibitors,
      cytidylyl(2'-->5')guanosine (2',5'-CpG) and 2'-deoxycytidylyl(3'-->5')-2'
      deoxyguanosine (3',5'-dCpdG). Based on the ligand-induced chemical shift changes
      in RC-RNase and the NOE cross-peaks between RC-RNase and the inhibitors, the key
      residues involved in protein-inhibitor interaction have been identified. The
      inhibitors were found to bind in a "retro-binding" mode, with the guanine base
      bonded to the B1 subsite. The His103 residue was found to occupy the B state with
      the imidazole ring pointing away from the active site. The structure coordinates
      and the NMR restraints have been deposited in the Brookhaven Protein Data Bank
      (1bc4 and 1bc4mr, respectively).

PMID- 9761687
TI  - HIV-1 rev nuclear export signal binding peptides isolated by phage display.
AB  - The human immunodeficiency virus type 1 (HIV-1) Rev protein is absolutely
      essential in the viral replication cycle, where it induces the production of
      viral structural proteins. Rev functions in part by inducing the nuclear export
      of incompletely spliced mRNA species specified by the presence of an RNA element,
      the Rev response element (RRE). Several proteins implicated in RNA processing and
      nucleo-cytoplasmic transport have been shown to interact with Rev, however, their
      exact roles remain unknown. To map potential protein recognition sites within the
      Rev structure, we have screened a phage library, displaying random 15-mer
      peptides, and isolated clones exhibiting similar sequences that specifically
      interact with Rev. The binding sites on Rev of the corresponding synthetic
      peptides were characterised by protein footprinting, involving partial
      proteolysis of radioactively end-labelled Rev protein. Two of the peptides
      produced a significant footprint within the nuclear export signal of Rev, raising
      the possibility that they mimic the binding of cellular protein factors
      implicated in nuclear export.

PMID- 9761688
TI  - Short elastin-like peptides exhibit the same temperature-induced structural
      transitions as elastin polymers: implications for protein engineering.
AB  - Elastin is a major protein component of the vascular wall and is responsible for
      its unusual elastic properties. Polymers of its repeating VPGVG sequences have
      been synthesised and shown to exhibit an inverse temperature transition where, as
      temperature rises, the polymer collapses from an extended chain to a beta-spiral
      structure with three VPGVG units per turn, each pentamer adopting a type II beta
      turn conformation. These studies, however, have not established whether the
      temperature-driven conformational change is an intrinsic property of the
      individual pentameric sequences or a global, co-operative effect of many
      pentamers within the beta-spiral structure. Here, we examine by circular
      dichroism the behaviour of elastin-like peptides (VPGVG)n, where n varies between
      1 and 5. Remarkably, we find that all lengths of peptide undergo an extended left
      and right arrow beta-turn transition with increasing temperature, suggesting that
      the induction of the beta-spiral occurs at the level of single pentameric units.
      The origin of this effect is a positive DeltaS term for the transition. At 35
      degreesC, the average transition midpoint temperature, the value of TDeltaS is
      about 15 kcal mol-1. With larger oligomers (n=3), there is only a modest rise in
      DeltaS, suggesting that the dominant entropic effect resides within the monomer
      and that interactions between these units make only a small contribution to the
      energetics of the transition. Charges at the termini, and residue replacements or
      additions, regulate the transitions for the short peptides in a manner similar to
      that observed for the longer polymers. The behaviour of the same peptides in
      trifluoroethanol and SDS solutions is consistent with formation of the beta-turn
      being driven by interactions between non-polar groups. The significance of this
      behaviour for the rational design of temperature-induced responses in proteins is
      discussed.

PMID- 9761689
TI  - Equilibrium and kinetics of the folding of equine lysozyme studied by circular
      dichroism spectroscopy.
AB  - The equilibrium unfolding and the kinetics of unfolding and refolding of equine
      lysozyme, a Ca2+-binding protein, were studied by means of circular dichroism
      spectra in the far and near-ultraviolet regions. The transition curves of the
      guanidine hydrochloride-induced unfolding measured at 230 nm and 292.5 nm, and
      for the apo and holo forms of the protein have shown that the unfolding is well
      represented by a three-state mechanism in which the molten globule state is
      populated as a stable intermediate. The molten globule state of this protein is
      more stable and more native-like than that of alpha-lactalbumin, a homologous
      protein of equine lysozyme. The kinetic unfolding and refolding of the protein
      were induced by concentration jumps of the denaturant and measured by stopped
      flow circular dichroism. The observed unfolding and refolding curves both agreed
      well with a single-exponential function. However, in the kinetic refolding
      reactions below 3 M guanidine hydrochloride, a burst-phase change in the circular
      dichroism was present, and the burst-phase intermediate in the kinetic refolding
      is shown to be identical with the molten globule state observed in the
      equilibrium unfolding. Under a strongly native condition, virtually all the
      molecules of equine lysozyme transform the structure from the unfolded state into
      the molten globule, and the subsequent refolding takes place from the molten
      globule state. The transition state of folding, which may exist between the
      molten globule and the native states, was characterized by investigating the
      guanidine hydrochloride concentration-dependence of the rate constants of
      refolding and unfolding. More than 80% of the hydrophobic surface of the protein
      is buried in the transition state, so that it is much closer to the native state
      than to the molten globule in which only 36% of the surface is buried in the
      interior of the molecule. It is concluded that all the present results are best
      explained by a sequential model of protein folding, in which the molten globule
      state is an obligatory folding intermediate on the pathway of folding.

PMID- 9761690
TI  - Peptide models of local and long-range interactions in the molten globule state
      of human alpha-lactalbumin.
AB  - alpha-Lactalbumin, a small calcium-binding protein, forms an equilibrium molten
      globule state under a variety of conditions. A set of four peptides designed to
      probe the role of local interactions and the role of potential long-range
      interactions in stabilizing the molten globule of alpha-lactalbumin has been
      prepared. The first peptide consists of residues 20 through 36 of human alpha
      lactalbumin and includes the entire B-helix. This peptide is unstructured in
      solution as judged by CD. The second peptide is derived from residues 101 through
      120 and contains both the D and 310 helices. When this peptide is crosslinked via
      the native 28 to 111 disulfide to the B-helix peptide, a dramatic increase in
      helicity is observed. The crosslinked peptide is monomeric, as judged by
      analytical ultracentrifugation. The peptide binds 1-anilinonaphthalene-8
      sulphonate (ANS) and the fluorescence emission maximum of the construct is
      consistent with partial solvent exposure of the tryptophan residues. The peptide
      corresponding to residues 101 to 120 adopts significant non-random structure in
      aqueous solution at low pH. Two hydrophobic clusters, one involving residues 101
      through 104 and the other residues 115 through 119 have been identified and
      characterized by NMR. The hydrophobic cluster formed by residues 101 through 104
      is still present in a smaller peptide containing only residues 101 to 111 of
      alpha-lactalbumin. The cluster also persists in 6 M urea. A non-native, pH
      dependent interaction between the Y103 and H107 side-chains that was previously
      identified in the acid-denatured molten globule state was examined. This
      interaction was found to be more prevalent at low pH and may therefore be an
      example of a local interaction that stabilizes preferentially the acid-induced
      molten globule state.

PMID- 9761691
TI  - Prediction and structural characterization of an independently folding
      substructure in the src SH3 domain.
AB  - Previous studies of the conformations of peptides spanning the length of the
      alpha-spectrin SH3 domain suggested that SH3 domains lack independently folding
      substructures. Using a local structure prediction method based on the I-sites
      library of sequence-structure motifs, we identified a seven residue peptide in
      the src SH3 domain predicted to adopt a native-like structure, a type II beta
      turn bridging unpaired beta-strands, that was not contained intact in any of the
      SH3 domain peptides studied earlier. NMR characterization confirmed that the
      isolated peptide, FKKGERL, adopts a structure similar to that adopted in the
      native protein: the NOE and 3JNHalpha coupling constant patterns were indicative
      of a type II beta-turn, and NOEs between the Phe and the Leu side-chains suggest
      that they are juxtaposed as in the prediction and the native structure. These
      results support the idea that high-confidence I-sites predictions identify
      protein segments that are likely to form native-like structures early in folding.

PMID- 9761692
TI  - Crystal structure of carbonic anhydrase from Neisseria gonorrhoeae and its
      complex with the inhibitor acetazolamide.
AB  - The crystal structure of carbonic anhydrase from Neisseria gonorrhoeae has been
      solved to a resolution of 1.78 A by molecular replacement using human carbonic
      anhydrase II as a template. After refinement the R factor was 17.8%
      (Rfree=23.2%). There are two molecules per asymmetric unit (space group P21), but
      they have essentially identical structures. The fold of the N. gonorrhoeae enzyme
      is very similar to that of human isozyme II; 192 residues, 74 of which are
      identical in the two enzymes, have equivalent positions in the three-dimensional
      structures. This corresponds to 85% of the entire polypeptide chain of the
      bacterial enzyme. The only two cysteine residues in the bacterial enzyme, which
      has a periplasmic location in the cell, are connected by a disulfide bond. Most
      of the secondary structure elements present in human isozyme II are retained in
      N. gonorrhoeae carbonic anhydrase, but there are also differences, particularly
      in the few helical regions. Long deletions in the bacterial enzyme relative to
      human isozyme II have resulted in a considerable shortening of three surface
      loops. One of these deletions, corresponding to residues 128 to 139 in the human
      enzyme, leads to a widening of the entrance to the hydrophobic part of the active
      site cavity. Practically all the amino acid residues in the active site of human
      isozyme II are conserved in the N. gonorrhoeae enzyme and have similar structural
      positions. However, the imidazole ring of a histidine residue, which has been
      shown to function as a proton shuttle in the catalytic mechanism of the human
      enzyme, interacts with an extraneous entity, which has tentatively been
      identified as a 2-mercaptoethanol molecule from the crystallization medium. When
      this entity is removed by soaking the crystal in a different medium, the side
      chain of His66 becomes quite mobile. The structure of a complex with the
      sulfonamide inhibitor, acetazolamide, has also been determined. Its position in
      the active site is very similar to that observed in human carbonic anhydrase II.

PMID- 9761694
TI  - The wallace brey symposium 

PMID- 9761693
TI  - Structural and functional roles of heme binding module in globin proteins:
      identification of the segment regulating the heme binding structure.
AB  - To investigate structural and functional significance of a newly proposed
      structural unit in globins, the "heme binding module", we synthesized a "heme
      binding module"-substituted chimeric globin and characterized its function and
      structure. In our previous study we proposed that the heme binding module,
      corresponding to the segment from Leu(F1) to Phe(G5) in hemoglobin alpha-subunit,
      plays a key role in constructing the heme proximal structure in globins. The
      replacement of the heme binding module in myoglobin with that of hemoglobin alpha
      subunit converted the absorption spectra into that of the alpha-subunit, and, in
      the resonance Raman spectra, the vibration mode characteristic of myoglobin
      completely disappeared after the module replacement. The hyperfine-shifted NMR
      resonances for the cyanide-bound form of the module-substituted myoglobin also
      revealed that the orientation of the axial histidine is close to that of the
      alpha-subunit rather than that of myoglobin, while the deviations of the
      resonance positions of the NMR signals from the amino acid residues located in
      the distal site were subtle, supporting the preferential structural alterations
      in the heme proximal site. The present finding for the structural alterations in
      the module-substituted myoglobin confirms that the heme binding module can be a
      segment regulating the heme proximal structure in globin proteins.

PMID- 9761695
TI  - Intravascular and intracellular hepatic relaxivities of superparamagnetic
      particles: an isolated and perfused organ pharmacokinetics study.
AB  - The relative contributions of intravascular and intracellular compartments to the
      proton transverse relaxation of the isolated and excised rat liver were
      determined during the phagocytosis of superparamagnetic particles. The evolution
      of the proton transverse magnetization of the organ perfused with increasing
      doses of starch-coated magnetic microspheres was followed up using a Carr-Purcell
      Meiboom-Gill sequence with various echo times. From the multiexponential fit of
      the echo train, the amplitudes and the relaxation rates R2 of the liver tissue
      were obtained. The results clearly indicate that shortly after contrast medium
      administration, an internalization takes place which can be followed by the rapid
      and biphasic evolution of the transverse relaxation rate of the water protons. A
      very fast decaying component looking like an initial loss of the magnetization is
      observed together with an increase of the relaxation rate of the remaining water
      tissue. This regime is strongly dependent on both the echo time and the iron
      concentration, a behavior characteristic of the agglomeration of magnetic
      particles. The examination of the liver tissues by electron microscopy shows that
      this clustering arises in cytoplasmic vacuoles.

PMID- 9761696
TI  - Image-based reduction of artifacts in multishot echo-planar imaging.
AB  - The method to reduce the ghost artifact in echo-planar imaging (EPI) using a
      phase correction derived from the image data (M. H. Buonocore and L. Gao, Magn.
      Reson. Med. 38, 89 (1997)) is generalized to multishot (interleaved) EPI, where
      the artifact takes the form of multiple ghosts. The method is shown to be much
      more sensitive to noise when applied to standard interleaved data than is the
      case with single-shot EPI, because the calculation must be based on high-order
      ghosts of low intensity. A modified interleaving scheme is proposed for multishot
      EPI in which the initial trajectory direction alternates in consecutive shots and
      the number of shots is odd. With this scheme, only a single ghost shifted by one
      half of the field of view appears just as in the single-shot EPI, and the image
      based phase correction can be applied with the usual sensitivity to noise.

PMID- 9761697
TI  - In vivo 3D localized 13C spectroscopy using modified INEPT and DEPT.
AB  - The 3D localized 13C spectroscopy methods LINEPT and LODEPT, which are
      modifications of INEPT and DEPT, are proposed. As long as a 13C inversion pulse
      (180-degree pulse) is applied at 1/(4J) before the proton echo time in LINEPT and
      a 13C excitation pulse (90-degree pulse) is applied at 1/(2J) before the proton
      echo time in LODEPT, the proton echo time can be set to any value longer than
      1/(2J) in LINEPT and longer than 1/J in LODEPT. As a result, the proton and the
      13C pulses can be applied separately and these proton pulses can be made slice
      selective pulses. These localization features of LINEPT and LODEPT were evaluated
      using a phantom consisting of a cylinder filled with ethanol placed inside
      another cylinder filled with oil, and localized ethanol spectra could be
      obtained. In vivo 3D localized 13C spectra from the brain of a monkey could be
      obtained using decoupled LINEPT, and glutamate C-4 appeared directly after the
      administration of glucose C-1, followed by the appearance of glutamate C-2, C-3
      and glutamine C-2, C-3, C-4.

PMID- 9761698
TI  - Evolution strategy optimization for selective pulses in NMR 
AB  - We present a first set of improved selective pulses, obtained with a numerical
      technique similar to the one proposed by Geen and Freeman. The novelty is
      essentially a robust and efficient "evolution strategy" which consistently leads,
      in a matter of minutes, to "solutions" better than those published so far. The
      other two ingredients are a "cost function," which includes contributions from
      peak and average radiofrequency power, and some understanding of the peculiar
      requirements of each type of pulse. For example, good solutions for self
      refocusing pulses and "negative phase excitation pulses" (which yield a maximum
      signal well after the end of the pulse) are found, as may have been predicted,
      among amplitude modulated pulses with 270 degrees tip angles. Emphasis is given
      to the search for solutions with low RF power for selective excitation,
      saturation, and inversion pulses. Experimental verification of accuracy and power
      requirements of the pulses has been performed with a 4.7 T Sisco imager.
      Copyright 1998 Academic Press.

PMID- 9761699
TI  - A high-precision carbon-13 shift thermometer for the temperature range 100-300 K 
AB  - The first carbon-13 shift thermometer for the temperature range of 100-300 K is
      based on the very rapid equilibration of a pair of semibullvalene valence
      tautomers. The temperature dependence of the equilibrium constant is reflected in
      strongly temperature-dependent shift differences Deltadelta between averaged
      signals, e.g., d(Deltadelta)/dT = 0.051 ppm K-1 at 300, 0.087 ppm K-1 at 200, and
      0. 175 ppm K-1 at 110 K for the quaternary carbon atoms C2 and C6. At 37
      temperatures T, which were measured with calibrated platinum resistance
      thermometers, shift differences Deltadelta were taken from nondecoupled carbon-13
      spectra recorded from solutions of 1 in mixtures of chlorodifluoromethane and
      deuterated dimethyl ether without spinning. The least-squares fit of these
      Deltadelta vs T data to a polynomial equation of the fourth degree (Eq. [5], r2 =
      0. 9999) allows the calculation of temperatures from measured shift differences
      with a standard deviation of 0.46 K and an estimated error of about 1 K. The
      heating effects of WALTZ-16 decoupling and the influence of solvents on
      Deltadelta are investigated. A comparison with existing NMR thermometers
      demonstrates the superior performance of the new carbon-13 shift thermometer with
      respect to precision and the accessible temperature range. Copyright 1998
      Academic Press.

PMID- 9761700
TI  - Diffusion measurements using radiofrequency field gradient: artifacts, remedies,
      practical hints 
AB  - The two major advantages of experiments carried out with radiofrequency (RF)
      field-gradient NMR are the instrumental simplicity and the insensitivity to
      background static magnetic field gradients. These features combined with large RF
      gradients, which became available only recently, should make this technique
      especially attractive for molecular translational diffusion studies. However, a
      critical evaluation of the method shows that under some circumstances (small
      and/or heterogeneous samples, weak diffusion coefficients, very short relaxation
      times) the quality of measurements may be affected by a number of artifacts.
      Their origin has been investigated and several remedies have been considered; in
      particular, a new improved sequence is presented. The success of various
      experimental tests demonstrates the efficiency of the proposed solutions which
      thus open the way to much wider application fields. Copyright 1998 Academic
      Press.

PMID- 9761702
TI  - Direct determination of motional correlation times by 1D MAS and 2D exchange NMR
      techniques 
AB  - One- and two-dimensional static and magic-angle spinning (MAS) exchange NMR
      experiments for quantifying slow (tauc > 1 ms) molecular reorientation dynamics
      are analyzed, emphasizing the extent to which motional correlation times can be
      extracted directly from the experimental data. The static two-dimensional (2D)
      exchange NMR experiment provides geometric information, as well as exchange time
      scales via straightforward and model-free application of Legendre-type
      orientational autocorrelation functions, particularly for axially symmetric
      interaction tensors, as often encountered in solid-state 2H and 13C NMR. Under
      conditions of MAS, increased sensitivity yields higher signal-to-noise spectra,
      with concomitant improvement in the precision and speed of correlation time
      measurements, although at the expense of reduced angular (geometric) resolution.
      For random jump motions, one-dimensional (1D) exchange-induced sidebands (EIS)
      13C NMR and the recently developed ODESSA and time-reverse ODESSA experiments
      complement the static and MAS two-dimensional exchange NMR experiments by
      providing faster means of obtaining motional correlation times. For each of these
      experiments, the correlation time of a dynamic process may be obtained from a
      simple exponential fit to the integrated peak intensities measured as a function
      of mixing time. This is demonstrated on polycrystalline dimethylsulfone, where
      the reorientation rates from EIS, ODESSA, time-reverse ODESSA, and 2D exchange
      are shown to be equivalent and consistent with literature values. In the
      analysis, the advantages and limitations of the different methods are compared
      and discussed. Copyright 1998 Academic Press.

PMID- 9761701
TI  - 2D CP/MAS 13C isotropic chemical shift correlation established by 1H spin
      diffusion.
AB  - A new 2D solid-state CP/MAS 13C NMR exchange experiment for through-space
      isotropic chemical shift correlation is proposed and demonstrated. Through-space
      correlation is established via a second cross polarization from 13C to 1H and
      subsequent 1H spin diffusion. A third cross polarization results in the final 13C
      13C isotropic chemical shift correlation. The 1H spin diffusion time is a
      variable parameter allowing different mean square magnetization displacements to
      be probed. Experimental results on mixtures of differently 13C-labeled alanine
      and polyethylene indicate that this site-selective 2D technique can be used to
      characterize domain sizes and proximities over a wide range of length scales (1
      200 nm) in solids such as polymers or biological materials.

PMID- 9761703
TI  - Fourier reconstruction as a valid alternative to filtered back projection in
      iterative applications: implementation of Fourier spectral spatial EPR imaging.
AB  - The qualitative equivalence between the Fourier reconstruction (FR) algorithm and
      the filtered back projection (FBP) algorithm is demonstrated when all the
      different phase errors that can occur in FR are eliminated. The causes of phase
      errors are underlined and methods to eliminate them are presented. The practical
      comparison between FR and FBP has been evaluated on a numerical test image and
      the results are reported, demonstrating the qualitative equivalence. FR has the
      advantage of being very computationally efficient. In fact, the time spent to
      obtain the FR image was 1/20 of that used to obtain the FBP image. Because of the
      computational efficiency of FR and the good quality of the results obtained, an
      iterative version of FR has been used to implement the spectral-spatial imaging
      (SSI) algorithm in the field of electron paramagnetic resonance imaging (EPRI).
      An experimental example, demonstrating its good performance, is reported.

PMID- 9761705
TI  - A new method for the determination of the dynamic isotope effect and the
      deuterium quadrupole coupling constant in liquids 
AB  - Using a self-consistent NMR method, it is now possible to determine both the
      deuterium quadrupole coupling constant as well as the rotational dynamic isotope
      effect in liquids. We successfully tested the method on benzene for temperatures
      between 280 K and 293 K. The average value of 185(3) kHz for the coupling
      constant is compared with measurements in solid state and gas phase. As might be
      expected for liquids without hydrogen bonds, no difference can be detected. A
      rotational dynamic isotope effect of 6(3)% is observed. This value is
      significantly smaller than 20(5)%, the only other result reported in the
      literature. The results are corrected for the influence of vibrational motion.
      Copyright 1998 Academic Press.

PMID- 9761704
TI  - Localized spectroscopy from anatomically matched compartments: improved
      sensitivity and localization for cardiac 31P MRS in humans.
AB  - Several pioneering studies have demonstrated that localized 31P NMR spectroscopy
      of the human heart might become an important diagnostic tool in cardiology. The
      main limitation is due to the low sensitivity of these experiments, allowing only
      crude spatial resolution. We have implemented a three-dimensional version of
      SLOOP ("spectral localization with optimal pointspread function") on a clinical
      instrument. SLOOP takes advantage of all available a priori information to match
      the size and the shape of the sensitive volumes to the anatomical structures in
      the examined subject. Thus, SLOOP reduces the contamination from adjacent organs
      and improves the sensitivity compared to conventional techniques such as ISIS or
      chemical shift imaging (CSI). Initial studies were performed on six healthy
      volunteers at 1.5 T. The good localization properties are demonstrated by the
      absence of resonances from blood in the heart spectra, and by PCr-free spectra
      from the liver. Compared to conventional CSI, the signal-to-noise ratio of the
      SLOOP heart spectra was improved by approximately 30%. Taking into account the
      varying excitation angle in the inhomogeneous B1 field of the surface coil, the
      SLOOP model computes the local spin saturation at every point in space.
      Therefore, no global saturation correction is required in the quantitative
      evaluation of local spectra. In this study, we found a PCr/gamma-ATP ratio in the
      left ventricular wall of 1.90 +/- 0.33 (mean +/- standard deviation).

PMID- 9761706
TI  - Improved estimation of CSA-dipolar coupling cross-correlation rates from
      laboratory-frame relaxation experiments 
AB  - We have investigated the underlying assumptions in estimating cross-correlation
      rates between chemical shift anisotropy (CSA) and dipolar coupling mechanisms in
      a scalar-coupled two-spin IS system, from laboratory frame relaxation
      experiments. It has been shown that for an arbitrary relaxation delay, the
      difference in relaxation rates of the individual components of an in-phase (or
      antiphase) doublet is not related to the CSA-dipolar coupling cross-correlation
      rate in a simple way. This is especially true in the case where the difference in
      the decay rates of the in-phase and antiphase terms of the density matrix becomes
      comparable to the magnitude of the scalar coupling between the two spins.
      Improved means of extracting cross-correlation rates in these cases are
      presented. Copyright 1998 Academic Press.

PMID- 9761707
TI  - A vector model of adiabatic decoupling 
AB  - A vector model of adiabatic decoupling is enunciated for an IS-coupled system of
      two spin-(1/2) heteronuclei in the high-power limit of ideal adiabatic pulses.
      The observed S-spin magnetization evolves according to a time-dependent coupling
      that scales as the z component of an I-spin vector which evolves due to the
      applied decoupling irradiation. Simple analytical expressions are derived both on
      and off resonance for the reduced coupling during an ideal sech/tanh inversion
      pulse and for the resulting signal when either in-phase or antiphase
      magnetization is present at the start of decoupling. The resulting model allows
      one to readily envision decoupling experiments, make accurate estimates of
      sideband intensity, and assess the relative performance of different decoupling
      schemes. The utility of the model is further demonstrated by applying it to
      several recently proposed methods for reducing sidebands. In the limit of ideal
      adiabatic pulses, the predictions of the vector model are almost identical to
      those of quantum mechanics. At the lower RF power levels used in practical
      adiabatic decoupling applications, where the pulses are no longer perfectly
      adiabatic, phase cycles are employed to achieve performance that approximates the
      ideal limits derived here, so the vector model is more generally applicable, as
      well. These limits establish standards for future determination of the most
      efficient parameters for practical applications of broadband adiabatic decoupling
      in a single transient. Copyright 1998 Academic Press.

PMID- 9761708
TI  - Calibration of STUD+ parameters to achieve optimally efficient broadband
      adiabatic decoupling in a single transient 
AB  - To provide the most efficient conditions for spin decoupling with least RF power,
      master calibration curves are provided for the maximum centerband amplitude, and
      the minimum amplitude for the largest cycling sideband, resulting from STUD+
      adiabatic decoupling applied during a single free induction decay. The principal
      curve is defined as a function of the four most critical experimental input
      parameters: the maximum amplitude of the RF field, RFmax, the length of the
      sech/tanh pulse, Tp, the extent of the frequency sweep, bwdth, and the coupling
      constant, Jo. Less critical parameters, the effective (or actual) decoupled
      bandwidth, bweff, and the sech/tanh truncation factor, beta, which become more
      important as bwdth is decreased, are calibrated in separate curves. The relative
      importance of nine additional factors in determining optimal decoupling
      performance in a single transient are considered. Specific parameters for
      efficient adiabatic decoupling can be determined via a set of four equations
      which will be most useful for 13C decoupling, covering the range of one-bond
      13C1H coupling constants from 125 to 225 Hz, and decoupled bandwidths of 7 to 100
      kHz, with a bandwidth of 100 kHz being the requirement for a 2 GHz spectrometer.
      The four equations are derived from a recent vector model of adiabatic
      decoupling, and experiment, supported by computer simulations. The vector model
      predicts an inverse linear relation between the centerband and maximum sideband
      amplitudes, and it predicts a simple parabolic relationship between maximum
      sideband amplitude and the product JoTp. The ratio bwdth/(RFmax)2 can be viewed
      as a characteristic time scale, tauc, affecting sideband levels, with tauc
      approximately Tp giving the most efficient STUD+ decoupling, as suggested by the
      adiabatic condition. Functional relationships between bwdth and less critical
      parameters, bweff and beta, for efficient decoupling can be derived from Bloch
      equation calculations of the inversion profile for a single sech/tanh pulse.
      Residual splitting of the centerband, normally associated with incomplete or
      inefficient decoupling, is not seen in sech/tanh decoupling and therefore cannot
      be used as a measure of adiabatic decoupling efficiency. The calibrated
      experimental performance levels achieved in this study are within 20% of
      theoretical performance levels derived previously for ideal sech/tanh decoupling
      at high power, indicating a small scope for further improvement at practical RF
      power levels. The optimization procedures employed here will be generally
      applicable to any good combination of adiabatic inversion pulse and phase cycle.
      Copyright 1998 Academic Press.

PMID- 9761709
TI  - Unambiguous correlations of backbone amide and aliphatic gamma resonances in
      deuterated proteins.
AB  - Two 3D NMR pulse sequences that correlate aliphatic gamma carbon resonance
      frequencies to amide proton and nitrogen chemical shifts in perdeuterated
      proteins are presented. The HN(COCACB)CG provides only interresidue
      connectivities (NH(i) and Cgamma(i-1)) while the HN(CACB)CG detects both the
      inter- and intraresidue (NH(i) and Cgamma(i) or Cgamma(i-1)) correlations. These
      two experiments are useful for sequential assignments and the identification of
      residue type from the Cgamma shifts. Spectra acquired on a perdeuterated 53-kDa
      protein illustrate the sensitivity and utility of these experiments.

PMID- 9761710
TI  - Pulsed field gradient selection in two-dimensional magic angle spinning NMR
      spectroscopy of dipolar solids 
AB  - The utility of gradient selection in MAS spectroscopy of dipolar solids is
      explored in two examples. In the first, rotor-synchronized gradients of
      appropriate strength and duration are applied to select 1H double-quantum
      coherences. The resulting DQ MAS spectrum of adamantane is compared with that
      acquired by the corresponding phase-cycling technique. As a second example, a 1H
      2D exchange MAS experiment is performed on an elastomer sample. In this
      experiment, a gradient is applied to remove undesired coherences that would
      otherwise distort the spectrum for short mixing times. The diagonal-peak
      intensities in the resulting spectrum show a linear decrease with increasing
      mixing time indicating cross-relaxation by slow chain motions as the relevant
      process. Both types of experiments demonstrate the potential of gradient
      selection techniques for MAS spectroscopy of dipolar solids. Copyright 1998
      Academic Press.

PMID- 9761711
TI  - High magnetic field consequences on the NMR hyperfine shifts in solution 
AB  - Pseudocontact shifts arise from the isotropic reorientational average of the
      dipolar coupling between unpaired electron and nuclei, in the presence of
      magnetic susceptibility anisotropy. The effect of residual orientation due to
      high magnetic fields on pseudocontact shifts is evaluated here. The effect is
      found to be smaller and of opposite sign with respect to another novel effect of
      high magnetic fields on hyperfine shifts due to saturation of the electron spin
      magnetic moment as described by the Brillouin equation. Copyright 1998 Academic
      Press.

PMID- 9761713
TI  - Meetings calendar 

PMID- 9761712
TI  - Measurement of dipolar couplings for methylene and methyl sites in weakly
      oriented macromolecules and their use in structure determination.
AB  - A simple and effective method is described for simultaneously measuring dipolar
      couplings for methine, methylene, and methyl groups in weakly oriented
      macromolecules. The method is a J-modulated 3D version of the well-known [1H-13C]
      CT-HSQC experiment, from which the J and dipolar information are most accurately
      extracted by using time-domain fitting in the third, constant-time dimension. For
      CH2-sites, the method generally yields only the sum of the two individual 13C-1H
      couplings. Structure calculations are carried out by minimizing the deviation
      between the measured sum, and the sum predicted for each methylene on the basis
      of the structure. For rapidly spinning methyl groups the dipolar contribution to
      the splitting of the outer 13C quartet components can be used directly to
      constrain the orientation of the C-CH3 bond. Measured sidechain dipolar couplings
      are in good agreement with an ensemble of NMR structures calculated without use
      of these couplings.

PMID- 9761715
TI  - The cysteine-string domain of the secretory vesicle cysteine-string protein is
      required for membrane targeting.
AB  - The post-translational addition of palmitic acid residues to cysteine-string
      protein (Csp) was originally thought to form the basis for membrane association
      of this secretory-vesicle protein. However, subsequent work showed that chemical
      depalmitoylation of Csp does not result in its release from membranes. We have
      confirmed these findings and employed [3H]palmitate labelling of PC12 cells to
      demonstrate that Csp1 remains associated with membranes following the complete
      removal of palmitic acid residues. Although palmitoylation is not essential for
      the stable membrane association of Csp, its role in membrane targeting has not
      been assessed. To examine this, we constructed a Csp mutant protein with seven
      cysteines replaced by serines in the cysteine-string domain. In contrast to wild
      type Csps, this mutant protein was not targeted to membranes when expressed in
      PC12 or HeLa cells. We conclude that although a palmitoylated cysteine-string
      domain is not required for stable membrane association of Csp, it is essential
      for initial membrane targeting.

PMID- 9761716
TI  - Circe's haemoglobins, pig-human hybrids: functional characterization and
      structural considerations.
AB  - We report the isolation and the functional characterization of alpha and beta
      chains from pig (Sus scropha domesticus) haemoglobin, as well as of the pig-human
      hybrid haemoglobins, alpha2(h)beta2(p) and alpha2(p)beta2(h) (i.e. Circe's
      haemoglobins), obtained by mixing the purified alpha and beta pig chains
      respectively with the corresponding partner human chains. Their functional
      properties have been compared with those of both parental haemoglobins in order
      to obtain information on the role of the different subunits and of their inter
      relationships, both at the structural and functional levels. The results indicate
      that the functional properties of both hybrids are closer to those of the
      parental haemoglobin that provides the beta chains, confirming the major role of
      the beta chains in determining the oxygen affinity and the modulation mechanisms
      of the tetrameric molecule. This is supported by the thermodynamic properties,
      since the very low DeltaH of oxygen binding that characterizes pig haemoglobin
      and the alpha2(h)beta2(p) hybrid haemoglobin may be taken as the reflection of
      specific structural properties of pig beta chain.

PMID- 9761714
TI  - Genetic engineering in mice: impact on insulin signalling and action.
AB  - The expression of a number of genes encoding key players in insulin signalling
      and action, including insulin, insulin receptor (IR), downstream signalling
      molecules such as insulin receptor substrate-1 (IRS-1) and IRS-2, glucose
      transporters (GLUT4, GLUT2) and important metabolic enzymes such as glucokinase,
      has now been altered in transgenic or knockout mice. Such mice presented with
      phenotypes ranging from mild defects, revealing complementarity between key
      molecules or pathways, to severe diabetes with ketoacidosis and early postnatal
      death. Insulin action could also be improved by overproduction of proteins acting
      at regulatory steps. The development of diabetes by combining mutations, which
      alone do not lead to major metabolic alterations, validated the 'diabetogenes'
      concept of non-insulin-dependent diabetes mellitus. Genes encoding insulin-like
      growth factors (IGF-I and IGF-II) and their type I receptor (IGF-IR) have also
      been disrupted. It appears that although IR and IGF-IR are both capable of
      metabolic and mitogenic signalling, they are not fully redundant. However, IR
      could replace IGF-IR if efficiently activated by IGF-II. Studies with cell lines
      lacking IR or IGF-IR lend support to such conclusions. Concerning the issues of
      specificity and redundancy, studies with cell lines derived from IRS-1-deficient
      mice showed that IRS-1 and IRS-2 are also not completely interchangeable.

PMID- 9761717
TI  - Purification and characterization of autophagosomes from rat hepatocytes.
AB  - To investigate the properties and intracellular origin of autophagosomes, a
      procedure for the purification and isolation of these organelles from rat liver
      has been developed. Isolated hepatocytes were incubated with vinblastine to
      induce autophagosome accumulation; the cells were then homogenized and treated
      with the cathepsin C substrate glycyl-l-phenylalanine 2-naphthylamide to cause
      osmotic disruption of the lysosomes. Nuclei were removed by differential
      centrifugation, and the postnuclear supernatant was fractionated on a
      discontinuous Nycodenz density gradient. The autophagosomes, recognized by their
      content of autophagocytosed lactate dehydrogenase (LDH), could be recovered in an
      intermediate-density fraction, free from cytosol and mitochondria. Finally, the
      autophagosomes were separated from the endoplasmic reticulum and other membranous
      elements by centrifugation in a Percoll colloidal density gradient, followed by
      flotation in iodixanol to remove the Percoll particles. The final autophagosome
      preparation represented a 24-fold purification of autophagocytosed LDH relative
      to intact cells, with a 12% recovery. The purified autophagosomes contained
      sequestered cytoplasm with a normal ultrastructure, including mitochondria,
      peroxisomes and endoplasmic reticulum in the same proportions as in intact cells.
      However, immunoblotting indicated a relative absence of cytoskeletal elements
      (tubulin, actin and cytokeratin), which may evade autophagic sequestration. The
      autophagosomes showed no enrichment in protein markers typical of lysosomes (acid
      phosphatase, cathepsin B, lysosomal glycoprotein of 120 kDa), endosomes (early
      endosome-associated protein 1, cation-independent mannose 6-phosphate receptor,
      asialoglycoprotein receptor) or endoplasmic reticulum (esterase, glucose
      regulated protein of 78 kDa, protein disulphide isomerase), suggesting that the
      sequestering membranes are not derived directly from any of these organelles, but
      rather represent unique organelles (phagophores).

PMID- 9761718
TI  - The insertion of human apolipoprotein H into phospholipid membranes: a monolayer
      study.
AB  - Apolipoprotein H (ApoH) is a plasma glycoprotein isolated from human serum. The
      interactions of ApoH with lipid membrane were reported to be essential for its
      physiological and pathogenic roles. In this paper we studied the ability of ApoH
      to insert into phospholipid membranes using the monolayer approach. The results
      show that ApoH is surface active and can insert into the lipid monolayers. The
      insertion ability of ApoH is stronger when a higher content of negatively charged
      lipids is present in the membrane. The acidic-pH and low-ionic-strength
      conditions will also enhance ApoH insertion, but these factors may not have much
      influence on the final insertion ability of ApoH, suggesting that, in the
      mechanism of ApoH insertion, not only electrostatic forces, but also hydrophobic
      interactions, are evidently involved. Modification by heat inactivation and
      reduction/alkylation does not change the critical insertion pressure (pic) of
      ApoH, suggesting a stable domain, maybe a linear sequence motif, but not the
      native three-dimensional structure of ApoH, is responsible for its insertion. The
      extent to which insertion of ApoH into phospholipid membranes may facilitate the
      'immune cleaning' of plasma liposomes is discussed.

PMID- 9761719
TI  - Oxidation of DNA bases, deoxyribonucleosides and homopolymers by peroxyl
      radicals.
AB  - DNA base oxidation is considered to be a key event associated with disease
      initiation and progression in humans. Peroxyl radicals (ROO. ) are important
      oxidants found in cells whose ability to react with the DNA bases has not been
      characterized extensively. In this paper, the products resulting from ROO.
      oxidation of the DNA bases are determined by gas chromatography/MS in comparison
      with authentic standards. ROO. radicals oxidize adenine and guanine to their 8
      hydroxy derivatives, which are considered biomarkers of hydroxyl radical (HO.)
      oxidations in cells. ROO. radicals also oxidize adenine to its hydroxylamine, a
      previously unidentified product. ROO. radicals oxidize cytosine and thymine to
      the monohydroxy and dihydroxy derivatives that are formed by oxidative damage in
      cells. Identical ROO. oxidation profiles are observed for each base when exposed
      as deoxyribonucleosides, monohomopolymers and base-paired dihomopolymers. These
      results have significance for the development, utilization and interpretation of
      DNA base-derived biomarkers of oxidative damage associated with disease
      initiation and propagation, and support the idea that the mutagenic potential of
      N-oxidized bases, when generated in cellular DNA, will require careful
      evaluation. Adenine hydroxylamine is proposed as a specific molecular probe for
      the activity of ROO. in cellular systems.

PMID- 9761720
TI  - Stimulation of gene expression in neonatal rat ventricular myocytes by Ras is
      mediated by Ral guanine nucleotide dissociation stimulator (Ral.GDS) and
      phosphatidylinositol 3-kinase in addition to Raf.
AB  - Treatment of cultured neonatal ventricular myocytes with oncogenic Ras increases
      their size and stimulates the re-expression of genes which are normally
      restricted to the fetal stage of ventricular development, including atrial
      natriuretic factor (ANF) and skeletal muscle (SkM)-alpha-actin. To determine
      which signalling pathways mediate these responses, myocytes were transfected with
      oncogenic (V12) Ras mutants which interact selectively with different effectors
      and their effects on luciferase (LUX) reporter plasmids were examined. V12 human
      Ras (V12HRas), itself, activated ANF-LUX 9. 6-fold, whereas mutants of V12HRas,
      which selectively stimulate Ral guanine nucleotide dissociation stimulator
      (Ral.GDS) (E37G), c-Raf (D38E) and phosphatidylinositol 3-kinase (PI-3-K; Y40C)
      enhanced ANF-LUX expression 3.0-, 3.7- and 1.7-fold respectively. The full
      response of ANF-LUX to V12HRas was restored by using a combination of the
      individual effector domain mutants. Likewise, SkM-alpha-actin-LUX expression was
      activated 12.0-, 3.5-, 4.5- and 3. 0-fold by V12HRas, E37G, D38E and Y40C
      respectively, and a similar pattern of activation was also observed using a c-fos
      serum-response element-LUX reporter gene. Cell size was also increased by each of
      the mutants, but simultaneous expression of all three mutant constructs was
      needed to reconstitute the full effect of V12HRas on cell size (50% increase).
      Transfection with a constitutively active mutant of PI-3-K (p110K227E) stimulated
      ANF-LUX, SkM-alpha-actin-LUX, c-fos-serum-response element-LUX and Rous sarcoma
      virus-LUX by 3.1-, 3.2-, 2.1- and 2.9-fold respectively, but the co-transfected
      cytomegalovirus-beta-galactosidase reporter gene was activated to a similar
      extent (1.9-fold). These results suggest that Raf, Ral.GDS and PI-3-K can all
      transduce transcriptional responses to V12HRas, but that the specific induction
      of genes associated with the hypertrophic response is not mediated through PI-3
      K.

PMID- 9761721
TI  - Modulation of RGD sequence motifs regulates disintegrin recognition of alphaIIb
      beta3 and alpha5 beta1 integrin complexes. Replacement of elegantin alanine-50
      with proline, N-terminal to the RGD sequence, diminishes recognition of the
      alpha5 beta1 complex with restoration induced by Mn2+ cation.
AB  - Several recent studies have demonstrated that the amino acid residues flanking
      the RGD sequence of high-affinity ligands modulate their specificity of
      interaction with integrin complexes. The present study has addressed the role of
      the residues flanking the RGD sequence in regulating the recognition by
      disintegrin of the alphaIIb beta3 and alpha5beta1 complexes by construction of a
      panel of recombinant molecules of Elegantin (the platelet aggregation inhibitor
      from the venom of Trimerasurus elegans) expressing specific RGD sequence motifs.
      Wild-type Elegantin (ARGDNP) and several variants including Eleg. AM (ARGDMP),
      Eleg. PM (PRGDMP) and Eleg. PN (PRGDNP) were expressed as glutathione S
      transferase (GST) fusion proteins in Escherichia coli. The inhibitory efficacies
      of the panel of Elegantin variants were analysed in platelet adhesion assays with
      substrates immobilized with fibrinogen and fibronectin. Elegantin molecules
      containing an Ala residue N-terminal to the RGD sequence (wild-type Elegantin and
      Eleg. AM) showed strong inhibitory activity towards alphaIIbbeta3-dependent
      platelet adhesion on fibronectin, whereas a Pro residue in this position (Eleg.
      PM and Kistrin, the inhibitor from the venom of Calloselasma rhodostoma)
      engendered lower activity. The decreased activity could not be attributed to a
      decrease in the affinity of the disintegrin for the alphaIIb beta3 complex
      because both Eleg. AM and Eleg. PM had similar Kd (app) values. In contrast,
      Elegantin molecules into which a Met residue was introduced in place of the Asn
      residue C-terminal to the RGD sequence showed 10-13-fold elevated inhibitory
      activity towards platelet adhesion on fibrinogen and this was maintained with
      either a Pro or Ala residue N-terminal to the RGD sequence. In experiments with
      the alpha5 beta1 complex on K562 cells, the inhibitory efficacies of the panel of
      Elegantin molecules were analysed under two different cation conditions. First,
      in the presence of Ca2+/Mg2+, K562 cell adhesion on fibronectin was inhibited
      equally well by Elegantin and Eleg. AM but inhibited poorly by Eleg. PM and
      Kistrin. In contrast with platelets, the decreased inhibitory efficacy of the
      PRGDMP disintegrins was due to poor recognition of the alpha5 beta1 complex. In
      the presence of Mn2+ cation, K562 cell adhesion on fibrinogen was observed in an
      alpha5 beta1-dependent manner. Under these conditions both PRGD and ARGD
      containing disintegrins were strong inhibitors of K562 cell adhesion on
      fibrinogen and this was due to a markedly improved recognition of the alpha5
      beta1 complex by the PRGD molecules. These observations demonstrate the pivotal
      role of the amino acids flanking the RGD sequence for disintegrin recognition of
      integrin complexes and highlight the subtle nature by which integrin-ligand
      binding specificity can be modulated by both cation and adhesive motif.

PMID- 9761722
TI  - The mouse ADP-ribosylation factor-like 4 gene: two separate promoters direct
      specific transcription in tissues and testicular germ cell.
AB  - ADP-ribosylation factor-like protein 4 (ARL4) is a Ras-related GTPase that has
      been cloned from the 3T3-L1 preadipocyte cell line as an adipocyte-specific cDNA
      [Schurmann, Breiner, Becker, Huppertz, Kainulainen, Kentrup and Joost (1994) J.
      Biol. Chem. 269, 15683-15688]. The Arl4 gene maps to the proximal region of mouse
      chromosome 12 linked to Lamb1-1, Hfhbf1 and Sos2. Compared with all other known
      genes of Ras-related GTPases, the genomic organization of Arl4 is unusual in that
      its entire coding region, the 3' untranslated region (UTR) and most of the 5' UTR
      are located on a single exon. This structure suggests that Arl4 has evolved by
      retroposition of an Arf (ADP-ribosylation factor) or Arf-like gene. Isolation of
      the 5' UTR by rapid amplification of cDNA ends (RACE)-PCR revealed heterogeneous
      transcription initiation sites in alternative exons 1. Both 5'-flanking regions
      exhibited promoter activity when expressed in COS-7 cells, indicating that the
      expression of Arl4 is directed by two separate promoters. mRNA transcribed under
      the control of the downstream promoter was isolated by RACE-PCR from all
      investigated tissues. In contrast, the upstream promoter seems to drive
      specifically the expression of Arl4 in adult testis. Hybridization of rat testis
      in situ indicated that Arl4 is expressed in germ cells of puberal and adult
      testis, but not in prepuberal testis, suggesting that Arl4 is involved in sperm
      production.

PMID- 9761723
TI  - Cloning and characterization of GETS-1, a goldfish Ets family member that
      functions as a transcriptional repressor in muscle.
AB  - An Ets transcription factor family member, GETS-1, was cloned from a goldfish
      retina cDNA library. GETS-1 contains a conserved Ets DNA-binding domain at its N
      terminus and is most similar to ternary complex factor (TCF) serum-response
      factor protein-1a (SAP-1a). GETS-1 is expressed in many tissues, but is enriched
      in retina and brain. As with the TCFs SAP-1a and ets-related protein (ERP),
      overexpression of the GETS-1 promoter suppresses nicotinic acetylcholine receptor
      epsilon-subunit gene expression in cultured muscle cells. A consensus Ets binding
      site sequence in the promoter of the epsilon-subunit gene is required for GETS-1
      mediated repression. GETS-1 repressor activity is abrogated by overexpression of
      an activated Ras/mitogen-activated protein kinase (MAP kinase) or by mutation of
      Ser-405, a MAP kinase phosphorylation site in GETS-1. Fusion proteins created
      between GETS-1 and the Gal4 DNA-binding domain show that, like other TCFs, GETS-1
      contains a C-terminal activation domain that is activated by a Ras/MAP kinase
      signalling cascade. Interestingly, mutation of Ser-405 located within this
      activation domain abrogated transcriptional activation of the fusion protein.

PMID- 9761725
TI  - The rate of sphingomyelin synthesis de novo is influenced by the level of
      cholesterol in cultured human skin fibroblasts.
AB  - Plasma membrane sphingomyelin (SM) is known to affect the cellular distribution
      of cholesterol. The aim of this work was to examine how SM homoeostasis in human
      skin fibroblasts is affected by alterations in the level of cholesterol in the
      cell. The cellular cholesterol level was decreased by exposing cells to 2
      hydroxypropyl-beta-cyclodextrin, and increased by exposing cells to cholesterol
      methyl-beta-cyclodextrin inclusion complexes. A lowering of the cellular
      unesterified cholesterol content by 20% was shown to increase the incorporation
      of [14C]palmitic acid into SM by 70%. Subsequently, the cellular SM mass was
      shown to be increased (24% increase after a 24 h period). Since l-cycloserine
      completely abolished the increased incorporation of [14C]palmitic acid into SM in
      cholesterol-depleted cells, we concluded that the de novo synthesis of the
      sphingosine backbone of SM was activated in cholesterol-depleted cells. This
      conclusion was further verified by performing a cell-free assay of serine C
      palmitoyltransferase (SPT) in cholesterol-depleted cells, which showed that the
      activity of the enzyme was increased by 30% after cholesterol depletion. Most of
      the newly synthesized SM in cholesterol-depleted cells was susceptible to
      degradation by sphingomyelinase, indicating that it was transported efficiently
      to the cell surface. Loading of fibroblasts with cholesterol had essentially the
      opposite effects on SM homoeostasis to those of cholesterol depletion, i.e. 20
      30% decreased incorporation of [14C]palmitic acid into SM and decreased activity
      of SPT. The results of this study show that cellular cholesterol levels have
      marked effects on the homoeostasis of SM.

PMID- 9761724
TI  - Functional analysis of the T-cell-restricted protein tyrosine kinase Txk.
AB  - T lymphocytes express a range of tyrosine kinases that are involved in signalling
      processes driving cell activation, proliferation and differentation. Two tyrosine
      kinases expressed only in T cells, the Itk/Emt and Txk gene products, are members
      of the Tec family of kinases. The role of Tec kinases in cellular function is
      poorly understood, although a Tec kinase specific to B cells, Btk, is essential
      for B-cell development. To explore the contribution of the T-cell-specific Tec
      kinases to lymphocyte function, we have expressed human Txk in the baculovirus
      system and conducted the first characterization of its activity. We find that Txk
      exhibits a substrate preference in vitro quite distinct from that of the major T
      cell kinases Lck and ZAP70, suggesting that Tec-family kinases might act on a
      distinct range of substrates. We also investigated the interactions of Txk with
      the cytoplasmic domains of the key signalling molecules CD3zeta, CD28 and CTLA4
      and find that none of these are phosphorylated by Txk, nor are they ligands for
      the SH2 or SH3 domains of Txk. We conclude that it is unlikely that Txk has a
      role in the early signal transduction events associated with these key pathways
      controlling T-cell activation.

PMID- 9761727
TI  - Evidence for the presence of multiple forms of Sph kinase in human platelets.
AB  - The intracellular distribution of sphingosine (Sph) kinase activity was examined
      in human platelets. A large proportion (72%) of the total activity was found to
      be associated with the membrane fraction, and the membrane-associated fraction
      had higher specific activity compared with the cytosolic enzyme. Most of the
      membrane-associated activity could be extracted with 1 M NaCl. The cytosolic
      activity was unstable upon heat treatment, with 80% of the activity being lost
      during incubation at 45 degreesC for 1 h, whereas the NaCl-extractable fraction
      was stable under the same conditions. When subjected to Mono Q column
      chromatography, the cytosolic fraction produced two activity peaks and the NaCl
      extractable fraction gave a single peak. These three Sph kinase activities showed
      different responses to stimulation by beta-octylglucoside and inhibition by N, N
      dimethylsphingosine and l-threo-dihydrosphingosine, suggesting the presence of
      multiple enzyme forms in human platelets.

PMID- 9761726
TI  - Effect of nutritional state on the formation of a complex involving insulin
      receptor IRS-1, the 52 kDa Src homology/collagen protein (Shc) isoform and
      phosphatidylinositol 3'-kinase activity.
AB  - The Src homology and collagen protein (Shc) is tyrosine phosphorylated in
      response to insulin; however, evidence for its interaction with insulin receptor
      (IR) in normal tissues is missing. Interactions between IR, Shc and regulatory
      subunits of the phosphatidylinositol 3'-kinase (PI 3'-kinase) were characterized
      in the present study in liver and muscles of chickens submitted to various
      nutritional states. A chicken liver Shc cDNA fragment encoding a 198 amino acid
      long fragment, including the phosphotyrosine binding domain was sequenced. It
      shows 89% homology with the corresponding human homologue. The amounts of the
      three Shc isoforms (66, 52 and 46 kDa) and Shc messenger were not altered by the
      nutritional state. Shc tyrosine phosphorylation was decreased by fasting in both
      liver and muscle. Importantly, Shc was immunoprecipitated by IR antibody (mostly
      the 52 kDa isoform) or by alphaIRS-1(mostly the 46 kDa isoform). IR-Shc
      association was decreased by fasting and restored by refeeding. In liver,
      alphaShc immunoprecipitated the three forms of regulatory subunits of PI 3'
      kinase and a PI 3'-kinase activity which was decreased by fasting. In muscle,
      alphaShc immunoprecipitated only the p85 isoform; the associated PI 3'-kinase
      activity was not altered by the nutritional state. Conversely, in both tissues
      anti-p85 antibody precipitated only the 52 kDa Shc isoform. In liver, antibodies
      to insulin receptor substrate-1 (alphaIRS-1), Shc or IR immunoprecipitated the
      three regulatory subunits of PI 3'-kinase and an equal PI 3'-kinase activity,
      without any residual activity left in the supernatants, suggesting the presence
      of a large complex involving IR, IRS-1, Shc (mainly the 52 kDa isoform) and PI 3'
      kinase activity. The presence of another complex containing IRS-1 and the 46 kDa
      Shc isoform, but no PI 3'-kinase activity, is suggested.

PMID- 9761728
TI  - Characterization of the hypertonically induced tyrosine phosphorylation of
      erythrocyte band 3.
AB  - Human erythrocyte band 3 becomes rapidly phosphorylated on tyrosine residues
      after exposure of erythrocytes to hypertonic conditions. The driving force for
      this phosphorylation reaction seems to be a decrease in cell volume, because (1)
      changes in band 3 phosphotyrosine content accurately track repeated changes in
      erythrocyte volume through several cycles of swelling and shrinking; (2) the
      level of band 3 phosphorylation is independent of the osmolyte employed but
      strongly sensitive to the magnitude of cell shrinkage; and (3) exposure of
      erythrocytes to hypertonic buffers under conditions in which intracellular
      osmolarity increases but volume does not change (nystatin-treated cells) does not
      promote an increase in tyrosine phosphorylation. We hypothesize that shrinkage
      induced tyrosine phosphorylation results either from an excluded-volume effect,
      stemming from an increase in intracellular crowding, or from changes in membrane
      curvature that accompany the decrease in cell volume. Although the net
      phosphorylation state of band 3 is shown to be due to a delicate balance between
      a constitutively active tyrosine phosphatase and constitutively active tyrosine
      kinase, the increase in phosphorylation during cell shrinkage was demonstrated to
      derive specifically from an activation of the latter. Further, a peculiar
      inhibition pattern of the volume-sensitive erythrocyte tyrosine kinase that
      matched that of p72syk, a tyrosine kinase already known to associate with band 3
      in vivo, suggested the involvement of this kinase in the volume-dependent
      response.

PMID- 9761729
TI  - Energy requirements for two aspects of phospholipid metabolism in mammalian
      brain.
AB  - Previous estimates have placed the energy requirements of total phospholipid
      metabolism in mammalian brain at 2% or less of total ATP consumption. This low
      estimate was consistent with the very long half-lives (up to days) reported for
      fatty acids esterified within phospholipids. However, using an approach featuring
      analysis of brain acyl-CoA, which takes into account dilution of the precursor
      acyl-CoA pool by recycling of fatty acids, we reported that half-lives of fatty
      acids in phospholipids are some 100 times shorter (min-h) than previously
      thought. Based on these new estimates of short half-lives, palmitic acid and
      arachidonic acid were used as prototype fatty acids to calculate energy
      consumption by fatty acid recycling at the sn-1 and sn-2 positions of brain
      phospholipids. We calculated that the energy requirements for reacylation of
      fatty acids into lysophospholipids are 5% of net brain ATP consumption. We also
      calculated ATP requirements for maintaining asymmetry of the aminophospholipids,
      phosphatidylserine and phosphatidylethanolamine across brain membrane bilayers.
      This asymmetry is maintained by a translocase at a stoichiometry of 1 mol of ATP
      per mol of phospholipid transferred in either direction across the membrane. The
      energy cost of maintaining membrane bilayer asymmetry of aminophospholipids at
      steady-state was calculated to be 8% of total ATP consumed. Taken together,
      deacylation-reacylation and maintenance of membrane asymmetry of
      phosphatidylserine and phosphatidylethanolamine require about 13% of ATP consumed
      by brain as a whole. This is a lower limit for energy consumption by processes
      involving phospholipids, as other processes, including phosphorylation of
      polyphosphoinositides and de novo phospholipid biosynthesis, were not considered.

PMID- 9761730
TI  - Evidence for a major structural change in Escherichia coli chorismate synthase
      induced by flavin and substrate binding.
AB  - Chorismate synthase (EC 4.6.1.4) catalyses the conversion of 5
      enolpyruvylshikimate 3-phosphate (EPSP) into chorismate, and requires reduced FMN
      as a cofactor. The enzyme can bind first oxidized FMN and then EPSP to form a
      stable ternary complex which does not undergo turnover. This complex can be
      considered to be a model of the ternary complex between enzyme, EPSP and reduced
      FMN immediately before catalysis commences. It is shown that the binding of
      oxidized FMN and EPSP to chorismate synthase affects the properties and structure
      of the protein. Changes in small-angle X-ray scattering data, decreased
      susceptibility to tryptic digestion and altered Fourier-transform (FT)-IR spectra
      provide the first strong evidence for major structural changes in the protein.
      The tetrameric enzyme undergoes correlated screw movements leading to a more
      overall compact shape, with no change in oligomerization state. The changes in
      the FT-IR spectrum appear to reflect changes in the environment of the secondary
      structural elements rather than alterations in their distribution, because the
      far-UV CD spectrum changes very little. Changes in the mobility of the protein
      during non-denaturing PAGE indicate that the ternary complex may exhibit less
      conformational flexibility than the apoprotein. Increased enzyme solubility and
      decreased tryptophan fluorescence are discussed in the light of the observed
      structural changes. The secondary structure of the enzyme was investigated using
      far-UV CD spectroscopy, and the tertiary structure was predicted to be an alpha
      beta-barrel using discrete state-space modelling.

PMID- 9761731
TI  - Mammalian cell polyamine homeostasis is altered by the radioprotector WR1065.
AB  - Mammalian cells become more susceptible to radiation-induced death and
      mutagenesis when restricted in their production of the natural polyamines
      putrescine, spermidine and spermine. The effects of polyamine deprivation are
      reversed by N-(2-mercaptoethyl)-1, 3-diaminopropane (WR1065), a simple aminothiol
      that has been extensively studied for its radioprotectant properties. Because
      this compound and its oxidized derivative WR33278 bear some resemblance to the
      polyamines, it was hypothesized that radioprotection by WR1065 or its metabolites
      is derived, at least in part, from their ability to supplement the natural
      polyamines. To evaluate the ability of these aminothiol compounds to emulate
      polyamine function in intact cells, rat liver hepatoma (HTC) cells were treated
      with radioprotective doses of WR1065; the ability of this compound to affect
      various aspects of normal polyamine metabolism was monitored. Although cellular
      WR1065 was maintained at levels exceeding those of the polyamines, this
      aminothiol did not have any polyamine-like effect on the initial polyamine
      biosynthetic enzyme, ornithine decarboxylase, or on polyamine degradative
      reactions. On the contrary, treatment with relatively low levels of WR1065
      resulted in an unexpected increase in putrescine and spermidine synthesis. WR1065
      treatment enhanced the stability, and consequently the activity, of ornithine
      decarboxylase. This stabilization seems to result from a WR1065-induced delay in
      the synthesis of antizyme, a critical regulatory protein required in the feedback
      modulation of polyamine synthesis and transport. The increase in cellular
      spermidine induced by WR1065 might explain its antimutagenic properties, but is
      probably not a factor in protection against cell killing by radiation. This is
      the first evidence that compounds can be designed to control polyamine levels by
      targeting the activity of the regulatory protein antizyme.

PMID- 9761732
TI  - The effects of a Ca2+ chelator and heavy-metal-ion chelators upon Ca2+
      oscillations and activation at fertilization in mouse eggs suggest a role for
      repetitive Ca2+ increases.
AB  - During fertilization in mouse eggs, the sperm triggers a series of intracellular
      Ca2+ oscillations that lead to egg activation, as indicated by pronuclear
      formation. We show that Ca2+ oscillations in fertilized mouse eggs can be
      inhibited by addition of either the Ca2+ chelator 1,2-bis-(o-aminophenoxy)ethane
      N,N,N',N'-tetra-acetic acid acetoxymethyl ester (BAPTA-AM) or the heavy-metal-ion
      chelator N,N,N',N'-tetrakis-(2-pyridylmethyl)ethylenediamine (TPEN) plus
      dithiothreitol (DTT). Both treatments inhibited Ca2+ oscillations, but they had
      different effects upon egg activation. Blocking Ca2+ oscillations with BAPTA-AM
      after the occurrence of just two Ca2+ spikes resulted in most eggs forming
      pronuclei. However, we found that BAPTA-AM-treated fertilizing eggs showed a
      decreased rate of protein synthesis, which by itself can promote egg activation.
      In contrast, blocking Ca2+ oscillations with TPEN plus DTT was accompanied by the
      inhibition of egg activation with no significant effect on protein synthesis. In
      eggs that were fertilized and then treated with TPEN plus DTT, there was a
      correlation between the number of Ca2+ spikes and the proportion of eggs that
      formed pronuclei, as well as between the number of Ca2+ spikes and the time taken
      for pronuclear formation and the first mitosis to occur. The addition of TPEN
      plus DTT did not block the generation of Ca2+ spikes or pronuclear formation when
      eggs were artificially stimulated by electroporation pulses. These data suggest
      that TPEN plus DTT inhibits pronuclear formation in fertilizing eggs via the
      inhibition of Ca2+ oscillations and that the number of Ca2+ spikes may regulate
      egg activation.

PMID- 9761733
TI  - Susceptibility towards intramolecular disulphide-bond formation affects
      conformational stability and folding of human basic fibroblast growth factor.
AB  - The conformational stability and the folding properties of the all-beta-type
      protein human basic fibroblast growth factor (hFGF-2) were studied by means of
      fluorescence spectroscopy. The results show that the instability of the
      biological activity of hFGF-2 is also reflected in a low conformational stability
      of the molecule. The reversibility of the unfolding and refolding process was
      established under reducing conditions. Determination of the free-energy of
      unfolding in the presence of reducing agents revealed that the conformational
      stability of hFGF-2 (DeltaGH2Oapp congruent with21 kJ. mol-1, 25 degreesC) is low
      compared with other globular proteins under physiological conditions (20-60
      kJ.mol-1). However, the conformational stability of hFGF-2 is particularly low
      under non-reducing conditions. This instability is attributed to intramolecular
      disulphide-bond formation, rendering the molecule more susceptible to denaturant
      induced unfolding. In addition, denaturant-induced unfolding of hFGF-2 renders
      the protein more susceptible to irreversible oxidative denaturation. Experimental
      evidence is provided that the irreversibility of the unfolding and refolding
      process in the absence of reducing agents is linked to the formation of an
      intramolecular disulphide bond involving cysteines 96 and 101.

PMID- 9761734
TI  - Phosphatidylinositol 4-kinase, but not phosphatidylinositol 3-kinase, is present
      in GLUT4-containing vesicles isolated from rat skeletal muscle.
AB  - Insulin stimulates the rate of glucose transport into muscle and adipose cells by
      translocation of glucose transporter (GLUT4)-containing vesicles from an
      intracellular storage pool to the surface membrane. This event is mediated
      through the insulin receptor substrates (IRSs), which in turn activate
      phosphatidylinositol (PI) 3-kinase isoforms. It has been suggested that insulin
      causes attachment of PI 3-kinases to the intracellular GLUT4-containing vesicles
      in rat adipose cells. Furthermore, it has also been shown that GLUT4-containing
      vesicles in adipose cells contain a PI 4-kinase. In the present study we
      investigate whether GLUT4-containing vesicles isolated from rat skeletal muscle
      display PI 3-kinase and/or PI 4-kinase activities. Insulin stimulation caused a
      rapid increase (5-15-fold increase compared with control) in the intracellular
      cytosolic IRS-1-associated PI-3 kinase activity. This PI 3-kinase activity was
      also present in a membrane preparation containing the insulin-regulatable pool of
      GLUT4 transporters. However, when GLUT4-containing vesicles were isolated by
      immunoprecipitation from basal and insulin-stimulated (3 min) skeletal muscle,
      the vesicles displayed PI 4-kinase, but not PI 3-kinase, activity. Insulin did
      not regulate the PI 4-kinase activity in the GLUT4-containing vesicles. In
      conclusion, GLUT4-containing vesicles from rat skeletal muscle contain a PI 4
      kinase, but not a PI 3-kinase. It is suggested that, in skeletal muscle, insulin
      causes activation of the IRS/PI 3-kinase complex in an intracellular membrane
      compartment associated closely with the GLUT4-containing vesicles, but not in the
      GLUT4-containing vesicles themselves.

PMID- 9761735
TI  - Voltammetric studies of the reactions of iron-sulphur clusters ([3Fe-4S] or [M3Fe
      4S]) formed in Pyrococcus furiosus ferredoxin.
AB  - Reactions of the [3Fe-4S] cluster and various metallated [M3Fe-4S] adducts co
      ordinated in the ferredoxin from the hyperthermophile Pyrococcus furiosus have
      been studied by protein-film voltammetry, bulk-solution voltammetry, solution
      kinetics and magnetic CD (MCD). The [3Fe-4S] cluster exhibits two couples, [3Fe
      4S]+/0 and [3Fe-4S]0/2-. Film voltammetry is possible over a wide pH range (2-8),
      revealing that the [3Fe-4S]+/0 couple shows a complex pH dependence with
      pKred1=2.8, pKox=4.9 and pKred2=6.7. From MCD, pKred1 corresponds with
      protonation of [3Fe-4S]0 to give a spectroscopically distinct species, as
      reported for ferredoxins from Azotobacter and Sulfolobus. The status of the
      disulphide/disulphydryl entity makes no significant difference to the data (given
      for the -S-S- form). Formation of the hyper-reduced [3Fe-4S]2- state is observed,
      requiring 3H+ for the overall 3e- reduction of [3Fe-4S]+, the change therefore
      being electroneutral. By comparison with the ferredoxin from Desulfovibrio
      africanus, uptake of Fe(II) and other M(II) by [3Fe-4S]0 to give [M3Fe-4S]
      clusters is slow (t1/2>10 min at room temperature, slower still if the protein is
      adsorbed on the electrode), whereas reaction with Tl(I) to produce [Tl3Fe-4S] is
      very rapid (t1/2<<1 s), suggesting that co-ordination of Tl does not require
      reorganization of the protein structure. Rates of formation of [3Fe-4S] from
      [M3Fe-4S] adducts increase sharply at high potentials, showing that metal release
      involves a labile 'super-oxidized' [M3Fe-4S]3+ state.

PMID- 9761736
TI  - Sulphated glycosaminoglycans prevent the neurotoxicity of a human prion protein
      fragment.
AB  - Although a number of features distinguish the disease isoform of the prion
      protein (PrPSc) from its normal cellular counterpart (PrPC) in the transmissible
      spongiform encephalopathies (TSEs), the neuropathogenesis of these diseases
      remains an enigma. The amyloid fibrils formed by fragments of human PrP have,
      however, been shown to be directly neurotoxic in vitro. We show here that
      sulphated polysaccharides (heparin, keratan and chondroitin) inhibit the
      neurotoxicity of these amyloid fibrils and this appears to be mediated via
      inhibition of the polymerization of the PrP peptide into fibrils. This provides a
      rationale for the therapeutic effects of sulphated polysaccharides and suggests a
      rapid in vitro functional screen for TSE therapeutics.

PMID- 9761737
TI  - Secondary structure analysis of the putative membrane-associated domains of the
      inward rectifier K+ channel ROMK1.
AB  - The inward rectifier K+ channels contain two putative membrane-spanning domains
      per subunit (M1, M2) and a 'pore' (P) region, which is similar to the H5 domain
      of voltage-gated K+ channels. Here we have used Fourier transform infrared (FTIR)
      and CD spectroscopy to analyse the secondary structures of synthetic peptides
      corresponding to the M1, M2 and P regions of ROMK1 in aqueous solution, in
      organic solvents and in phospholipid membranes. A previous CD study was unable to
      provide any structural data on a similar P peptide [Ben-Efraim and Shai (1997)
      Biophys. J. 72, 85-96]. However, our FTIR and CD spectroscopic analyses indicate
      that this peptide adopts an alpha-helical structure when reconstituted into
      dimyristoyl phosphatidylcholine vesicles and lysophosphatidyl choline (LPC)
      micelles as well as in trifluoroethanol (TFE) solvent. This result is in good
      agreement with a previous study on a peptide corresponding to the pore domain of
      a voltage-gated K+ channel [Haris, Ramesh, Sansom, Kerr, Srai and Chapman (1994)
      Protein Eng. 7, 255-262]. FTIR spectra of the M1 peptide in LPC micelles
      displayed a strong absorbance characteristic of an intermolecular beta-sheet
      structure, suggesting aggregation of the M1 peptide. Sucrose gradient
      centrifugation was used to separate aggregated peptide from peptide incorporated
      into micelles in an unaggregated manner; subsequent analysis by FTIR suggested
      that the M1 peptide adopted an alpha-helical structure when incorporated into
      phospholipid membranes. FTIR and CD spectra of the M2 peptide in phospholipids
      and high concentrations of TFE suggest that this peptide adopts an alpha-helical
      structure. The structural data obtained in these experiments have been used to
      propose a model for the structure of the membrane-associated core (M1-P-M2) of
      the inward rectifier K+ channel protein.

PMID- 9761738
TI  - Human MUC5AC mucin dimerizes in the rough endoplasmic reticulum, similarly to the
      MUC2 mucin.
AB  - Biosynthetic studies on the human MUC5AC mucin were performed by
      immunoprecipitations with antisera recognizing only the non-O-glycosylated
      apomucin in the colon adenocarcinoma cell line LS 174T. Pulse-chase studies and
      subcellular fractionations showed that MUC5AC formed dimers in the rough
      endoplasmic reticulum within 15 min of the initiation of biosynthesis. No non-O
      glycosylated species larger than dimers were identified. The dimerization was N
      glycosylation-dependent, because tunicamycin treatment significantly lowered the
      rate of dimerization. When the biosynthesis of MUC5AC apomucin was compared with
      that of MUC2 apomucin, also produced in the LS 174T cell line, both apomucins
      were assembled in similar ways with respect to their rates of dimerization with
      and without inhibition of N-glycosylation. No heterodimerization was observed
      between the human MUC5AC and the MUC2 apomucins despite the extensive sequence
      similarities in the positions of the cysteine residues in the C-termini proposed
      to be involved in mucin dimerization.

PMID- 9761739
TI  - Cytosolic deglycosylation process of newly synthesized glycoproteins generates
      oligomannosides possessing one GlcNAc residue at the reducing end.
AB  - Recent studies on the mechanism of degradation of newly synthesized glycoproteins
      suggest the involvement of a retrotranslocation of the glycoprotein from the
      lumen of the rough endoplasmic reticulum into the cytosol, where a
      deglycosylation process takes place. In the studies reported here, we used a
      glycosylation mutant of Chinese hamster ovary cells that does not synthesize
      mannosylphosphoryldolichol and has an increased level of soluble oligomannosides
      originating from glycoprotein degradation. In the presence of anisomycin, an
      inhibitor of protein synthesis, we observed an accumulation of glucosylated
      oligosaccharide-lipid donors (Glc3Man5GlcNAc2-PP-Dol), which are the precursors
      of the soluble neutral oligosaccharide material. Inhibition of rough endoplasmic
      reticulum glucosidase(s) by castanospermine led to the formation of
      Glc3Man5GlcNAc2(OSGn2) (in which OSGn2 is an oligomannoside possessing two GlcNAc
      residues at its reducing end), which was then retained in the lumen of
      intracellular vesicles. Thus they were protected during an 8 h chase period from
      the action of cytosolic chitobiase, which is responsible for the conversion of
      OSGn2 to oligomannosides possessing one GlcNAc residue at the reducing end
      (OSGn1). In contrast, when protein synthesis was maintained in the presence of
      castanospermine, glucosylated oligomannosides (Glc1-3Man5GlcNAc1) were recovered
      in cytosol. Except for monoglucosylated Man5 species, which are potential
      substrates for luminal calnexin and calreticulin, the pattern of oligomannosides
      was similar to that observed on glycoproteins. The occurrence in the cytosol of
      glucosylated species with one GlcNAc residue at the reducing end implies that the
      deglycosylation process that generates glucosylated OSGn1 from glycoproteins
      occurs in the cytosol.

PMID- 9761741
TI  - Crystal structure of the family 7 endoglucanase I (Cel7B) from Humicola insolens
      at 2.2 A resolution and identification of the catalytic nucleophile by trapping
      of the covalent glycosyl-enzyme intermediate.
AB  - Cellulose is the major polysaccharide component of the plant cell wall and the
      most abundant naturally produced macromolecule on Earth. The enzymic degradation
      of cellulose, by cellulases, is therefore of great environmental and commercial
      significance. Cellulases are found in 12 of the glycoside hydrolase families
      classified according to their amino acid sequence similarities. Endoglucanase I
      (Cel7B), from the soft-rot fungus Humicola insolens, is a family 7 enzyme. The
      structure of the native form of Cel7B from H. insolens at 2.2 A resolution has
      been solved by molecular replacement using the known Trichoderma reesei
      cellobiohydrolase I [Divne, Stahlberg, Reinikainen, Ruohonen, Pettersson,
      Knowles, Teeri and Jones (1994) Science 265, 524-528] structure as the search
      model. Cel7B catalyses hydrolysis of the beta-1,4 glycosidic linkages in
      cellulose with net retention of anomeric configuration. The catalytic nucleophile
      at the active site of Cel7B has been identified as Glu-197 by trapping of a 2
      deoxy-2-fluorocellotriosyl enzyme intermediate and identification of the labelled
      peptide in peptic digests by tandem MS. Site-directed mutagenesis of both Glu-197
      and the prospective catalytic acid, Glu-202, results in inactive enzyme,
      confirming the critical role of these groups for catalysis.

PMID- 9761740
TI  - Phosphatidylinositol 3'-kinase associates with an insulin receptor substrate-1
      serine kinase distinct from its intrinsic serine kinase.
AB  - Serine phosphorylation of insulin receptor substrate-1 (IRS-1) has been proposed
      as a counter-regulatory mechanism in insulin and cytokine signalling. Here we
      report that IRS-1 is phosphorylated by a wortmannin insensitive
      phosphatidylinositol 3'-kinase (PI 3-kinase)-associated serine kinase (PAS
      kinase) distinct from PI 3-kinase serine kinase. We found that PI 3-kinase immune
      complexes contain 5-fold more wortmannin-insensitive serine kinase activity than
      SH2-containing protein tyrosine phosphatase-2 (SHP2) and IRS-1 immune complexes.
      Affinity chromatography of cell lysates with a glutathione S-transferase fusion
      protein for the p85 subunit of PI 3-kinase showed that PAS kinase associated with
      the p85 subunit of PI 3-kinase. This interaction required unoccupied SH2
      domain(s) but did not require the PI 3-kinase p110 subunit binding domain. In
      terms of function, PAS kinase phosphorylated IRS-1 and, after insulin
      stimulation, PAS kinase phosphorylated IRS-1 in PI 3-kinase-IRS-1 complexes.
      Phosphopeptide mapping showed that insulin-dependent in vivo sites of IRS-1
      serine phosphorylation were comparable to those of PAS kinase phosphorylated IRS
      1. More importantly, PAS kinase-dependent phosphorylation of IRS-1 reduced by 4
      fold the ability of IRS-1 to act as an insulin receptor substrate. Taken
      together, these findings indicate that: (a) PAS kinase is distinct from the
      intrinsic serine kinase activity of PI 3-kinase, (b) PAS kinase associates with
      the p85 subunit of PI 3-kinase through SH2 domain interactions, and (c) PAS
      kinase is an IRS-1 serine kinase that can reduce the ability of IRS-1 to serve as
      an insulin receptor substrate.

PMID- 9761742
TI  - Atypical protein kinase Clambda binds and regulates p70 S6 kinase.
AB  - p70 S6 kinase (p70 S6K) has been implicated in the regulation of cell cycle
      progression. However, the mechanism of its activation is not fully understood. In
      the present work, evidence is provided that an atypical protein kinase C (PKC)
      isotype, PKClambda, is indispensable, but not sufficient, for the activation of
      p70 S6K. Both the regulatory and kinase domains of PKClambda associate directly
      with p70 S6K. Overexpression of the kinase domain without kinase activity or the
      regulatory domain of PKClambda results in the suppression of the serum-induced
      activation of p70 S6K. In addition, two types of dominant-negative mutants of
      PKClambda, as well as a kinase-deficient mutant of p70 S6K, suppress serum
      induced DNA synthesis and E2F activation. The overexpresion of the active form of
      PKClambda, however, fails to activate p70 S6K. These results suggest that
      PKClambda is a mediator in the regulation of p70 S6K activity and plays an
      important role in cell cycle progression.

PMID- 9761744
TI  - Effects of cholesterol depletion by cyclodextrin on the sphingolipid microdomains
      of the plasma membrane.
AB  - Sphingolipid microdomains are thought to result from the organization of plasma
      membrane sphingolipids and cholesterol into a liquid ordered phase, wherein the
      glycosylphosphatidylinositol (GPI)-anchored proteins are enriched. These domains,
      resistant to extraction by cold Triton X-100, can be isolated as buoyant membrane
      complexes (detergent-resistant membranes) in isopycnic density gradients. Here
      the effects of methyl-beta-cyclodextrin (MBCD), a specific cholesterol-binding
      agent that neither binds nor inserts into the plasma membrane, were investigated
      on the sphingolipid microdomains of lymphocytes. MBCD released substantial
      quantities of GPI-anchored Thy-1 and glycosphingolipid GM1, and also other
      surface proteins including CD45, and intracellular Lck and Fyn kinases. From
      endothelial cells, MBCD released GPI-anchored CD59, and CD44, but only a
      negligible amount of caveolin. Most MBCD-released Thy-1 and CD59 were not
      sedimentable and thus differed from Thy-1 released by membrane-active cholesterol
      binding agents such as saponin and streptolysin O, or Triton X-100. Unlike that
      released by Triton X-100, only part of the Thy-1 molecules released by MBCD was
      buoyant in density gradients and co-isolated with GM1. Finally, treatment of
      Triton X-100-isolated detergent-resistant membranes with MBCD extracted most of
      the cholesterol without affecting the buoyant properties of Thy-1 or GM1. We
      suggest that (1) MBCD preferentially extracts cholesterol from outside, rather
      than within the sphingolipid microdomains and (2) this partly solubilizes GPI
      anchored and transmembrane proteins from the glycerophospholipid-rich membrane
      and releases sphingolipid microdomains in both vesicular and non-vesicular form.

PMID- 9761743
TI  - Involvement of a local fenton reaction in the reciprocal modulation by O2 of the
      glucagon-dependent activation of the phosphoenolpyruvate carboxykinase gene and
      the insulin-dependent activation of the glucokinase gene in rat hepatocytes.
AB  - H2O2 mimicked the action of periportal pO2 in the modulation by O2 of the
      glucagon-dependent activation of the phosphoenolpyruvate carboxykinase (PCK) gene
      and the insulin-dependent activation of the glucokinase (GK) gene. H2O2 can be
      converted in the presence of Fe2+ in a Fenton reaction into hydroxyl anions and
      hydroxyl radicals (.OH). The hydroxyl radicals are highly reactive and might
      interfere locally with transcription factors. It was the aim of the present study
      to investigate the role of and to localize such a Fenton reaction. Hepatocytes
      cultured for 24 h were treated under conditions mimicking periportal or
      perivenous pO2 with glucagon or insulin plus the iron chelator desferrioxamine
      (DSF) or the hydroxyl radical scavenger dimethylthiourea (DMTU) to inhibit the
      Fenton reaction. PCK mRNA was induced by glucagon maximally under conditions of
      periportal pO2 and half-maximally under venous pO2. GK mRNA was induced by
      insulin with reciprocal modulation by O2. DSF and DMTU reduced the induction of
      PCK mRNA to about half-maximal and increased the induction of GK mRNA to maximal
      under both O2 tensions. Hydroxyl radical formation was maximal under arterial
      pO2. Perivenous pO2, DSF and DMTU each decreased the formation of .OH to about
      70% of control. The Fenton reaction could be localized in a perinuclear space by
      confocal laser microscopy and three-dimensional reconstruction techniques. In the
      same compartment, iron could be detected by electron-probe X-ray microanalysis.
      Thus a local Fenton reaction is involved in the O2 signalling, which modulated
      the glucagon- and insulin-dependent PCK gene and GK gene activation.

PMID- 9761745
TI  - Purification and biochemical characterization of a poly(ADP-ribose) polymerase
      like enzyme from the thermophilic archaeon Sulfolobus solfataricus.
AB  - A poly(ADP-ribose) polymerase-like enzyme, detected in a crude homogenate from
      Sulfolobus solfataricus by means of activity and immunoblot analyses, was
      purified to electrophoretic homogeneity by a rapid procedure including two
      sequential affinity chromatographies, on NAD+-agarose and DNA-Sepharose. The
      latter column selected specifically the poly(ADP-ribosyl)ating enzyme with a 17%
      recovery of enzymic activity and a purification of more than 15000-fold. The
      molecular mass (54-55 kDa) assessed by SDS/PAGE and immunoblot was definitely
      lower than that determined for the corresponding eukaryotic protein. The enzyme
      was proved to be thermophilic, with a temperature optimum of approx. 80 degreesC,
      and thermostable, with a half-life of 204 min at 80 degreesC, in good agreement
      with the requirements of a thermozyme. It displayed a Km towards NAD+ of 154+/-50
      microM; in the pH range 6.5-10.0 the activity values were similar, not showing a
      real optimum pH. The enzyme was able to bind homologous DNA, as evidenced by the
      ethidium bromide displacement assay. The product of the ADP-ribosylating reaction
      co-migrated with the short oligomers of ADP-ribose (less than 6 residues) from a
      eukaryotic source. Reverse-phase HPLC analysis of the products, after digestion
      with phosphodiesterase I, gave an elution profile reproducing that obtained by
      the enzymic digestion of the rat testis poly(ADP-ribose). These results strongly
      suggest that the activities of the purified enzyme include the elongation step.

PMID- 9761746
TI  - Identification of glu-277 as the catalytic nucleophile of Thermoanaerobacterium
      saccharolyticum beta-xylosidase using electrospray MS.
AB  - Thermoanaerobacterium saccharolyticum beta-xylosidase is a member of family 39 of
      the glycosyl hydrolases. This grouping comprises both retaining beta-d
      xylosidases and alpha-l-iduronidases. T. saccharolyticum beta-xylosidase
      catalyses the hydrolysis of short xylo-oligosaccharides into free xylose via a
      covalent xylosyl-enzyme intermediate. Incubation of T. saccharolyticum beta
      xylosidase with 2,4-dinitrophenyl 2-deoxy-2-fluoro-beta-d-xyloside resulted in
      time-dependent inactivation of the enzyme (inactivation rate constant ki=0.089
      min-1, dissociation constant for the inactivator Ki=65 microM) through the
      accumulation of a covalent 2-deoxy-2-fluoro-alpha-d-xylosyl-enzyme, as observed
      by electrospray MS. Removal of excess inactivator and regeneration of the free
      enzyme through transglycosylation with either xylobiose or thiobenzyl xyloside
      demonstrated that the covalent intermediate was kinetically competent. Peptic
      digestion of the 2-deoxy-2-fluoro-alpha-d-xylosyl-enzyme intermediate and
      subsequent analysis by electrospray ionization triple-quadrupole MS in the
      neutral-loss mode indicated the presence of a 2-deoxy-2-fluoro-alpha-d-xylosyl
      peptide. Sequence determination of the labelled peptide by tandem MS in the
      daughter-ion scan mode permitted the identification of Glu-277 (bold and
      underlined) as the catalytic nucleophile within the sequence IILNSHFPNLPFHITEY.

PMID- 9761747
TI  - Sialomucin complex at the rat ocular surface: a new model for ocular surface
      protection.
AB  - The ocular surface, which is among the most accessible and vulnerable tissues in
      mammals, is protected by a complex tear film composed of lipid, aqueous and mucin
      layers. In spite of its importance, the molecular nature of the mucin
      contribution remains uncertain. Since membrane mucins have been implicated in the
      protection of other epithelia, we have analysed rat corneal and conjunctival
      tissues for sialomucin complex (SMC), a membrane mucin found at the apical
      epithelial cell surfaces in the airway and uterus. Using Northern and Western
      blot analyses, SMC expression was found in both ocular tissues, being
      particularly abundant in the cornea. In contrast with the other known membrane
      mucin, MUC1, SMC was localized more heavily towards the apical surface of the
      epithelial cells. SMC in ocular surface epithelia was produced in both soluble
      and membrane forms, the latter being found predominantly in the most superficial
      cells and at apical surfaces. The soluble form was found loosely adsorbed to
      apical cell surfaces, particularly of the cornea, as indicated by a mild rinsing
      protocol. Finally, the tear fluid contained substantial amounts of SMC. From
      these results, we propose a new model for tear mucin components in which SMC is
      expressed at the apical ocular surface in both membrane-bound and adsorbed
      soluble forms to provide a direct protective barrier. SMC secreted into the tear
      fluid may also participate in maintaining the stability of the preocular tear
      film by acting with other secreted mucins to determine the physical properties
      and protective behaviour of the tear film.

PMID- 9761748
TI  - The function of cell adhesion molecules in lung inflammation: more questions than
      answers.

PMID- 9761749
TI  - Expression of Fas (CD95) and FasL (CD95L) in human airway epithelium.
AB  - The cell surface molecule Fas (CD95) is a member of the tumor necrosis factor
      receptor family. Ligation of the Fas receptor can lead to induction of apoptosis
      in inflammatory cells. It has been suggested that expression of the Fas receptor
      and its ligand (FasL) in airway epithelium may modulate the inflammatory response
      commonly found in asthmatic lungs. We examined Fas and FasL expression on primary
      human tissues, on bronchial epithelial cells in primary culture, and on the
      immortalized human airway epithelial cell line, 1HAEo-. Receptor and ligand
      expression were demonstrated using multiple antibodies and multiple techniques,
      including immunohistochemistry, flow cytometry, Western blots, and reverse
      transcription-polymerase chain reaction (RT-PCR). Immunohistochemical staining
      demonstrated that both columnar and basal cells of intact human lung tissues
      expressed cell surface Fas and FasL. In addition, both primary cultured and
      immortalized 1HAEo- cells expressed cell surface Fas and FasL, as demonstrated by
      flow cytometry; expression of Fas and FasL was confirmed at the transcription
      level using RT-PCR and, for additional confirmation of FasL, using Western blots.
      We demonstrate that both Fas and FasL are expressed by human airway epithelial
      cell subtypes. Expression of these molecules may play an important role in
      regulation of the inflammatory response.

PMID- 9761750
TI  - Increased endothelial cell expression of platelet-endothelial cell adhesion
      molecule-1 during hyperoxic lung injury.
AB  - Lung injury is a frequent consequence of oxygen (O2) therapy administered to
      newborns and adults with respiratory distress. Acute exposure to hyperoxia
      results in a well-described pathophysiologic response in the lungs. Because
      inflammation is an important component of pulmonary O2 toxicity, we have an
      interest in identifying the inflammatory mediators that increase during
      hyperoxia. Platelet-endothelial cell adhesion molecule-1 (PECAM-1), a member of
      the immunoglobulin superfamily that is expressed at the junctions between
      endothelial cells, is essential to the transendothelial migration of leukocytes.
      We hypothesized that increased expression of PECAM-1 occurs in pulmonary
      endothelial cells during hyperoxic lung injury. Adult mice were exposed to 100%
      O2 for up to 96 h. We analyzed PECAM-1 expression by RNA blot hybridization, in
      situ hybridization, and immunohistochemistry. A increase in PECAM-1 mRNA was seen
      as soon as 2 d of hyperoxia relative to unexposed control mice. PECAM-1 mRNA and
      protein were found in endothelial cells of both large and small arteries. The
      expression of PECAM-1 in capillary vessels was further confirmed using in situ
      hybridization at the electron microscope level. This increase in PECAM-1
      expression coincided with the appearance of leukocytes in lung tissue. These
      observations suggest that PECAM-1 expression is a relatively early step in the
      inflammation cascade, and intervention at this phase may be critical to the
      prevention of further damage.

PMID- 9761751
TI  - Expression of heterogeneous nuclear ribonucleoprotein A2/B1 changes with critical
      stages of mammalian lung development.
AB  - Recent reports have demostrated a link between expression of members of the
      family of heterogeneous nuclear ribonucleoproteins (hnRNPs) and cancer.
      Overexpression of hnRNP A2/B1 correlated with the eventual development of lung
      cancer in three different clinical cohorts. We have studied the expression of
      hnRNP A2/B1 messenger RNA (mRNA) and protein during mammalian development. The
      expression of hnRNP A2/B1 mRNA and protein are parallel but change dynamically
      during critical periods in mouse pulmonary development. hnRNP A2/B1 is first
      detected in the lung in the early pseudoglandular period, peaks at the beginning
      of the canalicular period, and remains high during the saccular (alveolar)
      period. In mouse and rat, hnRNP A2/B1 expression is first evident in the earliest
      lung buds. As lung development progresses, the cuboidal epithelial cells of the
      distal primitive alveoli show high levels of the ribonucleoprotein, which is
      almost undetectable in the proximal conducting airways. The expression of hnRNP
      A2/ B1 is restricted in mature lung. Similar dynamic pattern of expression
      through lung development was also found in rat and human lung. Upregulated
      expression of hnRNP A2/B1 at critical periods of lung development was comparable
      to the level of expression found in lung cancers and preneoplastic lesions and is
      consistent with hnRNP A2/B1 overexpression playing an oncodevelopmental role.

PMID- 9761752
TI  - Differential expression of fibroblast growth factor receptors 1 to 4 and ligand
      genes in late fetal and early postnatal rat lung.
AB  - To characterize fibroblast growth factor (FGF) gene expression in the late fetal
      (days E18 to E22) and early postnatal lung (days P0 to P28), when the alveolar
      region undergoes extensive growth and reorganization, we analyzed the expression
      of four FGF receptors and six ligands. FGF receptor 1 (FGFR1) RNA levels were
      first low (E18) before rising late in the postnatal period (P28). FGFR2 RNA
      levels were detected early (at E18) and then increased (E20-P0) before falling
      (P2) to below later postnatal levels (P6 to P28). FGFR3 RNA levels were low at
      first (E18) and then increased, with peak levels in the days after birth (P2 to
      P10). FGFR4 RNA levels, barely detected in fetal lung (E18 to E22), increased at
      birth (P0) and remained high postnatally (P2 to P28). In fetal lung, FGF2 (basic
      FGF) RNA expression levels were low and FGF1 (acidic FGF) RNA levels were not
      detected: low RNA levels of each ligand were detected postnatally (P7 to P28).
      FGF3 to 5 and FGF7 RNA were not detected in fetal or postnatal lung. With in situ
      hybridization, predominantly the smooth muscle cells of large vessels expressed
      FGFR1 and 4 mRNA; the epithelial cells of large airways expressed FGFR1, 2, and
      4; and alveolar cells expressed FGFR2, 3, and 4. Analysis of protein expression
      first identified FGF2 localized to the basement membrane of large airways and
      branching epithelial buds, to mesenchymal cells associated with buds, to the
      putative smooth muscle cells of large airways and vessels, and to pleural- and
      mesenchymal-associated cells (E18). Immediately before birth, this pattern of
      expression persisted (E20 to E22), with FGF2 also being expressed by putative
      smooth muscle cells of smaller airways and vessels (E22). After birth (P0 to
      P28), FGF2 expression remained relatively high in the smooth muscle cells of
      large and small vessels and in pleural cells; in airway smooth muscle cells and
      in most cells in the alveolar region, however, although FGF2 expression persisted
      in some cells, its intensity decreased with time.

PMID- 9761754
TI  - Expression of lumican in human lungs.
AB  - The collagen-elastin-proteoglycan (PG) matrix is the key constituent of lung
      parenchyma and plays a major role in the mechanical behavior of lung tissues.
      However, the exact composition of the PG matrix in lungs has not yet been fully
      determined. In the present study we report the expression of leucine-rich repeat
      PGs in adult human lungs. PG extraction was performed on peripheral lung tissue
      from patients undergoing therapeutic lung resections. The samples were analyzed
      by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting
      using antipeptide antisera specific to human lumican, decorin, biglycan, and
      fibromodulin. Control experiments to verify antiserum reactivity were performed
      with an extract of adult human articular cartilage, which is known to contain all
      four PGs. In all lung extracts analyzed, a single component of molecular weight
      65 to 90 kD was detected for lumican. Decorin, biglycan, and fibromodulin were
      either not detected or were barely detectable in the lung extracts, but were
      readily visualized in the cartilage samples. Immunohistochemistry showed that
      lumican was diffusely present in peripheral lung tissue, mainly in vessel walls.
      These results suggest that lumican is a major component of the PG matrix in adult
      human lungs.

PMID- 9761753
TI  - Oxygen toxicity in mouse lung: pathways to cell death.
AB  - Mice exposed to 100% O2 die after 3 or 4 d with diffuse alveolar damage and
      alveolar edema. Extensive cell death is evident by electron microscopy in the
      alveolar septa, affecting both endothelial and epithelial cells. The damaged
      cells show features of both apoptosis (condensation and margination of chromatin)
      and necrosis (disruption of the plasma membrane). The electrophoretic pattern of
      lung DNA indicates both internucleosomal fragmentation, characteristic of
      apoptosis, and overall degradation, characteristic of necrosis. Hyperoxia induces
      a marked increase in RNA or protein levels of p53, bax, bcl-x, and Fas, which are
      known to be expressed in certain types of apoptosis. However, we did not detect
      an increased activity of proteases belonging to the apoptosis "executioner"
      machinery, such as CPP32 (caspase 3), ICE (caspase 1), or cathepsin D.
      Furthermore, administration of an ICE-like protease inhibitor did not
      significantly enhance the resistance to oxygen. Additionally, neither p53
      deficient mice nor lpr mice (Fas null) manifested an increased resistance to
      hyperoxia-induced lung damage. These results show that both necrosis and
      apoptosis contribute to cell death during hyperoxia. Multiple apoptotic pathways
      seem to be involved in this, and an antiapoptotic strategy does not attenuate
      alveolar damage.

PMID- 9761755
TI  - T and B cell independence of endothelial cell adhesion molecule expression in
      pulmonary granulomatous inflammation.
AB  - A pulmonary Cryptococcus neoformans (Cne: strain 52D, ATCC24067) infection model
      in mice was used to examine the possible role for T cell-mediated immunity in
      regulating vascular adhesion molecules on lung endothelium during development of
      granulomatous inflammation. Resolution of pulmonary Cne infection in C.B-17 mice
      begins by Day 14 following intratracheal inoculation and depends on T cell
      mediated recruitment of monocytes followed by their activation. C.B-17 scid/scid
      (SCID) mice mount a less exuberant pulmonary inflammatory response, recruit fewer
      monocytes into their lungs, and fail to clear the infection. Recruitment of
      leukocytes into infected tissue is mediated by both the interaction of adhesion
      molecules expressed on the surface of activated vascular endothelial cells with
      ligands on circulating cells, and the directed response of these leukocytes to
      chemotactic factors. The kinetics of expression of the endothelial cell adhesion
      molecules E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and
      intercellular adhesion molecule-1 (ICAM-1), all previously shown to regulate
      monocyte recruitment, were examined in the lungs of infected C.B-17 and SCID mice
      during pulmonary infection to determine if T cells were necessary for their
      upregulation. Immunohistochemical analysis showed that upregulation of E
      selectin, VCAM-1, and ICAM-1 did not differ significantly between C.B-17 and SCID
      mice at any time during infection. Maximal expression in C.B-17 and SCID mice was
      noted between Days 5 and 7 for all three molecules and preceded maximal influx of
      leukocytes into the lung. Thus, the inability of SCID mice to recruit optimal
      numbers of monocytes into infected lungs was not the result of a failure to
      express the critical adhesion molecules early in infection, but likely reflected
      absence of immune dependent chemotactic factors.

PMID- 9761756
TI  - Glucocorticoid-induced apoptosis of dendritic cells in the rat tracheal mucosa.
AB  - Dendritic cells are antigen-presenting cells that constitutively express high
      levels of major histocompatibility complex class II (Ia) antigen on their plasma
      membrane. Previous studies have shown that the number of dendritic cells in the
      rat airway mucosa decreases rapidly after glucocorticoid treatment. We sought to
      determine whether apoptosis contributes to this steroid-induced cell decrease.
      Dendritic cells in tracheal whole mounts were revealed by immunoperoxidase
      staining using the OX-6 (anti-Ia) monoclonal antibody. In untreated rats, a dense
      network of Ia-immunoreactive (Ia+) cells with highly branched cytoplasmic
      processes was observed just beneath the tracheal epithelium (1,405 +/- 140
      cells/mm2 mucosa; mean +/- SEM, n = 6). In rats treated with dexamethasone (10
      mg/kg, intraperitoneally), four distinct changes in dendritic cell morphology
      were evident 4 to 8 h after injection: (1) appearance of large Ia+ granules in
      cytoplasmic processes, (2) narrowing of cytoplasmic processes, (3) loss of Ia
      immunoreactivity from the cell surface, and (4) fragmentation of cells into small
      Ia+ bodies. These changes accompanied a 56% decrease in the number of Ia+ cells
      over 8 h. The contribution of apoptosis to this decrease in Ia+ cells was
      determined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end
      labeling (TUNEL) of nucleosomal DNA fragments in histologic sections. The number
      of TUNEL+ bodies increased from a control value of 174 +/- 47 bodies/mm2 mucosa
      to 2,108 +/- 294 bodies/mm2 mucosa at 4 h and 936 +/- 343 bodies/ mm2 mucosa at 8
      h (n = 4 rats per time point). The location of TUNEL+ bodies closely corresponded
      to that of Ia+ cells stained in adjacent histologic sections. We conclude that
      apoptosis contributes to the rapid decrease in airway dendritic cells after
      glucocorticoid treatment.

PMID- 9761758
TI  - SP-A2 gene expression in human fetal lung airways.
AB  - In the present study, we characterized surfactant protein (SP)-A messenger RNA
      (mRNA) in mid-trimester human fetal trachea and bronchi. SP-A protein was
      localized by immunocytochemistry to scattered epithelial cells in the airway
      surface epithelium and in submucosal glands of the fetal trachea and bronchi. SP
      A mRNA (2.2 kb) was detected by Northern blot analysis in human fetal trachea, as
      well as in primary and more distal bronchi. The levels of detectable SP-A mRNA
      were highest in the upper airways and were decreased in smaller bronchi in
      comparison. SP-A mRNA was barely detectable in the distal fetal lung tissue. In
      contrast, SP-A mRNA was abundant in cultured explants of distal human fetal lung
      tissue. SP-A1 and SP-A2 mRNA were detected by primer extension analysis in adult
      human lung tissue and in cultured human fetal lung explants. Only SP-A2 mRNA was
      detected in RNA isolated from human fetal trachea and bronchi. SP-A mRNA was
      localized by in situ hybridization in the fetal trachea and bronchi in scattered
      cells in the surface epithelium and, most prominently, in submucosal glands. Our
      results suggest that SP-A2, and not SP-A1, is produced in the human fetal
      tracheal and bronchial epithelium and in submucosal glands.

PMID- 9761757
TI  - Proliferation of human non-small-cell lung cancer cell lines: role of interleukin
      6.
AB  - Interleukin-6 (IL-6) is involved in regulation of the immune response, acute
      phase reaction, and cell proliferation. The aim of this study was to investigate
      whether IL-6 is implicated in cell proliferation of human non-small-cell lung
      cancer (NSCLC) cell lines. We analyzed IL-6 messenger RNA (mRNA) and protein
      expression in eight NSCLC cell lines: A549, Calu3, Calu6, H23, H522, H810, H1155,
      and H1299. The A549, Calu3, Calu6, and H23 cell lines expressed IL-6 mRNA and
      protein. In these cell lines, fetal calf serum (FCS) significantly increased cell
      proliferation as assessed by thymidine incorporation. In the presence of IL-6
      antisense oligonucleotides, both proliferation and IL-6 synthesis were
      downregulated. In contrast, IL-6 mRNA and protein could not be detected in the
      NSCLC cell lines H522, H810, H1155, and H1299. In these NSCLC cell lines, FCS
      only marginally increased cell proliferation and IL-6 antisense oligonucleotides
      did not affect cell proliferation. The addition of neither exogenous IL-6 nor
      neutralizing anti-IL-6 antibodies affected cell proliferation in any of the
      experiments. Our data thus provide evidence that intracellular IL-6 is required
      in the control of cell proliferation in a subset of human NSCLC cell lines. We
      suggest the existence of two subtypes of NSCLC, an IL-6-dependent and an IL-6
      independent type.

PMID- 9761759
TI  - Allergen immunotherapy inhibits airway eosinophilia and hyperresponsiveness
      associated with decreased IL-4 production by lymphocytes in a murine model of
      allergic asthma.
AB  - In the present study, we investigated whether allergen immunotherapy is effective
      in a murine model with immunologic and pathophysiologic features reminiscent of
      allergic asthma. Ovalbumin-sensitized mice received increasing (1 microgram to 1
      mg) subcutaneous doses of ovalbumin twice a week for 8 wk according to a semirush
      immunotherapy protocol as used in allergic patients. During immunotherapy, an
      initial rise in serum levels of ovalbumin-specific antibodies (immunoglobulin
      [Ig]G1, IgE, IgG2a) occurred, after which IgE levels decreased sharply
      concomitant with an increase in IgG2a levels. The increase in IgG2a levels, with
      the decline in IgE levels, suggests that during immunotherapy interferon-gamma
      production is increased or interleukin (IL)-4 production is decreased. After
      immunotherapy, inhalation challenge of the mice with ovalbumin revealed almost
      complete inhibition (98%, P < 0.01) of eosinophil infiltration into
      bronchoalveolar lavage and airway hyperresponsiveness (100% at 320 microgram/kg
      methacholine, P < 0.05) compared with sham-treated animals. In addition, IL-4
      production of thoracic lymph node cells stimulated with ovalbumin in vitro was
      largely reduced (60%, P < 0.05) after immunotherapy. Thus, effective
      immunotherapy in this animal model appears to be due to modulation of antigen
      specific T cells. Similar effects on airway symptoms and IL-4 production can be
      obtained within 1 wk by three injections of the highest dose of ovalbumin (1 mg).
      This animal model will be used as a preclinical model to improve allergen
      immunotherapy and to gain more insight into the mechanisms involved.

PMID- 9761760
TI  - Tumor necrosis factor-alpha stimulates human Clara cell secretory protein
      production by human airway epithelial cells.
AB  - Clara cell secretory protein (CCSP), or CC10, is an inhibitor of secretory
      phospholipase A2 which may be produced by phagocytic cells and by a variety of
      other cells in the airway. Tumor necrosis factor-alpha (TNF-alpha) is capable of
      activating phospholipases and inducing the expression of a variety of genes in
      the airway epithelium which may modulate the airway inflammatory response.
      Therefore, it was of interest to determine whether this proinflammatory cytokine
      could induce the production of a counterregulatory protein such as CCSP which
      might modulate the production of eicosanoid mediators in the airway. Using a
      human bronchial epithelial cell line (BEAS-2B), CCSP messenger RNA (mRNA) levels
      were detected by ribonuclease protection assay. TNF treatment of these cells
      increased CCSP mRNA levels in a time- and dose-dependent manner. The CCSP mRNA
      level increased in response to TNF-alpha (20 ng/ml) stimulation after 8 to 36 h
      with the peak increase at 18 h. Immunoblotting of CCSP protein released into the
      culture media demonstrated that TNF-alpha induced the synthesis and secretion of
      CCSP protein in a time-dependent manner over 8 to 18 h. The results of a CCSP
      reporter gene activity assay, nuclear run-on assay, and CCSP mRNA half-life assay
      indicated that the TNF-alpha-induced increases in CCSP gene expression are
      regulated at the post-transcriptional level. We conclude that TNF-alpha induces
      airway epithelial cell expression of human CCSP protein and may modulate airway
      inflammatory responses in this manner.

PMID- 9761761
TI  - Expression of the human integrin beta6 subunit in alveolar type II cells and
      bronchiolar epithelial cells reverses lung inflammation in beta6 knockout mice.
AB  - Inactivation of the integrin beta6 subunit gene in mice resulted in an unexpected
      phenotype-functionally significant inflammation of the skin and lungs. These
      findings suggested a role for ligation of the alphav beta6 integrin on epithelial
      cells in downregulating epithelial inflammation. However, the results of gene
      inactivation could have been due to inactivation of adjacent genes and provided
      no information about the role of this integrin in specific populations of
      epithelial cells. In the current study, we used transgenic mice constitutively
      expressing the human beta6 subunit in alveolar type II cells and bronchiolar
      epithelial cells to examine directly the significance of alphav beta6 in these
      cells. Expression of this transgene largely inhibited the increases in airspace
      lymphocytes and macrophages and the lymphocyte and macrophage activation caused
      by inactivation of the beta6 subunit gene, and reduced the peribronchial and
      perivascular accumulations of lymphocytes. In the genetically mixed mice used for
      this study, we identified airway eosinophilia as an additional effect of beta6
      inactivation. This effect was also partially inhibited by limited expression of
      the human transgene. These results definitively identify a role for distal lung
      epithelial alphav beta6 in downregulating pulmonary inflammation and suggest that
      interventions augmenting beta6 expression or function in these cells could
      influence the course of inflammatory lung diseases.

PMID- 9761762
TI  - The effect of chloride concentration on human neutrophil functions: potential
      relevance to cystic fibrosis.
AB  - Recently, some investigators have observed elevated concentrations of chloride in
      the airway surface fluid (ASF) overlying respiratory epithelia from cystic
      fibrosis (CF) patients compared with ASF overlying non-CF epithelia. Others have
      shown that this elevated ASF salt concentration can inactivate human beta
      defensin-1, an antimicrobial peptide secreted by respiratory epithelia. This
      could impair the primary epithelial defense against bacteria in the CF airway,
      thereby forcing a greater reliance on polymorphonuclear leukocyte (PMN)-mediated
      defenses. Pseudomonas aeruginosa (Psa) flourishes in the CF airway despite the
      presence of abundant PMN. We therefore investigated whether elevated ASF chloride
      concentration in CF might also compromise PMN function. We employed a cell
      culture model in which halide concentrations and osmolarity were varied
      independently. We examined the effects of chloride concentration on three aspects
      of PMN function: recruitment of PMN to the airway (production of interleukin-8
      [IL-8]), PMN antimicrobial activity (killing of Psa), and PMN clearance from the
      airways (apoptosis and lysis). We found that exposure to elevated chloride
      concentration increased PMN synthesis of IL-8, decreased PMN killing of Psa, and
      accelerated PMN apoptosis and lysis. In CF airways, elevated chloride therefore
      could contribute to the increased number of PMN recruited into the airways, the
      increased survival of Psa, and the increased quantity of toxic mediators released
      by PMN into the airways. These effects of elevated chloride on PMN function may
      provide another causal link between loss of cystic fibrosis transmembrane
      conductance regulator function and CF lung disease.

PMID- 9761763
TI  - Hypoxia-induced interleukin-6 and interleukin-8 production is mediated by
      platelet-activating factor and platelet-derived growth factor in primary human
      lung cells.
AB  - Hypoxia has been shown to induce the expression of different growth factors,
      cytokines, and proinflammatory mediators, including platelet-derived growth
      factor (PDGF), interleukin-6 (IL-6), interleukin-8 (IL-8), and platelet
      activating factor (PAF) in animal models. PAF and PDGF are thought to play
      important roles in vascular remodeling and have been shown to induce expression
      of IL-6 and IL-8 genes under normoxic conditions. We hypothesize that de novo
      synthesis of IL-6, IL-8, and cell proliferation is enhanced in human pulmonary
      cells under hypoxic cell culture conditions. We further assumed an important role
      of PAF and/or PDGF in hypoxia-induced cell activation. Using cultures of primary
      human pulmonary fibroblasts and pulmonary vascular smooth muscle cells (VSMC) we
      show that hypoxia (3% O2) induced transcription and translation of IL-6 (4- to 5
      fold) and IL-8 (5- to 6-fold) in both cell types. Hypoxia-induced expression of
      IL-6 was suppressed by 50% to 60% in the presence of the PAF antagonist WEB2170,
      or neutralizing anti-PDGF antibodies. In addition, we demonstrate that hypoxia
      induces a threefold increase of cell proliferation of fibroblasts and a twofold
      increase of VSMC proliferation. Similar to the effect on IL-6 and IL-8 synthesis,
      WEB2170 or neutralizing anti-PDGF antibodies downregulated hypoxia-induced
      proliferation of fibroblasts and VSMC by 50%. Our data show that PAF and PDGF are
      important mediators for hypoxia-induced cell activation and cytokine release in
      the human lung. We therefore hypothesize that IL-6 and IL-8 contribute to the
      progression of lung diseases associated with hypoxia, and that both
      proinflammatory factors, PAF and PDGF, are involved in hypoxia-dependent
      expression of IL-6 and IL-8 in human pulmonary fibroblasts and VSMC.

PMID- 9761764
TI  - Characterization of the gene and promoter for RTI40, a differentiation marker of
      type I alveolar epithelial cells.
AB  - In an effort to understand the processes that establish and maintain the
      differentiated state of the alveolar epithelium, we have analyzed the gene for
      rat type I cell 40 kD protein (RTI40), an apical integral plasma membrane protein
      expressed in type I but not type II alveolar epithelial cells. The RTI40 gene
      spans 35 kilobase pairs; it contains 6 exons and at least 6 rat Identifier
      repetitive elements. Three exons encode the predicted RTI40 extracellular domain
      and one encodes the single transmembrane spanning domain. The final exon encodes
      one amino acid followed by a stop codon. RTI40 gene transcription starts
      downstream from a TATA homology, which is immediately adjacent to putative
      binding sites for thyroid transcription factor 1 and Sp1. In H441 cell
      transfections, mutagenesis of a 5'-flanking fragment (-2496 to +104) revealed two
      regions that contribute to promoter activity: -1247 through -795 and -163 through
      -81. Heterologous promoter fusion experiments suggest that a cooperative
      interaction between these regions activates transcription. In transfected type II
      cells, deletion across the proximal region produced a 6-fold drop in promoter
      activity, whereas deletion across the distal region was without apparent effect.
      These results provide a foundation to analyze further the factors that govern
      alveolar epithelial cell phenotype.

PMID- 9761765
TI  - Induction of the lung myofibroblast PDGF receptor system by urban ambient
      particles from Mexico City.
AB  - Platelet-derived growth factor (PDGF) and its receptor system regulate
      mesenchymal cell proliferation. We recently reported that emission-source fly-ash
      particles and asbestos fibers induce the PDGF alpha-receptor through a macrophage
      dependent pathway, and upregulation of this receptor greatly enhances the
      mitogenic response of lung myofibroblasts to PDGF (Lindroos and colleagues, Am.
      J. Respir. Cell Mol. Biol. 1997;16:283-292). In the present study we investigated
      the effect of particulate matter <= 10 micrometers in size (PM10) from the
      southern, central, and northern regions of Mexico City on PDGF receptor induction
      and compared these urban, ambient particles with Mt. St. Helen's volcanic ash
      particles as a negative control. All Mexico City PM10 samples, but not volcanic
      ash, stimulated rat alveolar macrophages to secrete a soluble, upregulatory
      factor(s) for the PDGF alpha-receptor on early passage rat lung myofibroblasts.
      The macrophage-derived upregulatory activity was blocked by the interleukin (IL)
      1 receptor antagonist. The ability of PM10 to stimulate IL-1beta release was
      blocked in part by a recombinant endotoxin neutralizing protein (rENP).
      Lipopolysaccharide/endotoxin (LPS) and vanadium, both constituents that were
      present within these PM10 samples, also stimulated macrophages to secrete
      factor(s) that upregulated PDGF-Ralpha on lung myofibroblasts. Direct exposure of
      myofibroblasts to PM10 also elicited upregulation of the PDGF alpha-receptor, and
      this effect was blocked by rENP and mimicked by LPS, but not vanadium. These
      findings suggest that PM10 particles induce expression of the PDGF receptor
      system through macrophage-dependent and -independent mechanisms involving
      endotoxin and metals.

PMID- 9761766
TI  - Identification and characterization of high molecular-mass mucin-like
      glycoproteins in the plasma membrane of airway epithelial cells.
AB  - A previous lectin binding study demonstrated the presence of high molecular-mass
      mucin-like glycoproteins (HMGP) on the surface of hamster tracheal surface
      epithelial (HTSE) secretory cells (Proc. Natl. Acad. Sci. USA 1987;84:9304). In
      the present study, we intended to isolate and characterize these HMGP from the
      plasma membrane of the primary HTSE cells and then to determine whether or not
      these membrane HMGP are Muc-1 mucins, a type of mucins originally discovered on
      the surface of some carcinomas. A subcellular fraction enriched with the plasma
      membrane was obtained using a sucrose density gradient centrifugation. This
      fraction contained high molecular-mass glycoconjugates which were excluded from
      Sepharose CL-4B gel. Biochemical characterization of these glycoconjugates
      revealed the following characteristics: (1) susceptibility to both pronase and
      mild alkaline treatments, but totally resistant to proteoglycan-digesting
      enzymes; (2) partitioning in the detergent phase of Triton X-114 and resistance
      to digestion by phosphatidylinositol phospholipase C or D; (3) a buoyant density
      of 1.5 g/ml based on CsCl density gradient centrifugation; (4) polydispersity in
      terms of both size and charge density; and (5) lack of immunoreactivity with an
      anti-Muc-1 mucin antibody. We conclude that the plasma membrane of HTSE cells at
      confluence contains HMGP, which seem to be the integral membrane proteins but
      different from Muc-1 mucins, and that these membrane HMGP appear to share some
      similarities with secreted mucins in terms of size and charge.

PMID- 9761767
TI  - Human eosinophils constitutively express a functional interleukin-4 receptor:
      interleukin-4 -induced priming of chemotactic responses and induction of PI-3
      kinase activity.
AB  - Similar to interleukin-3 (IL-3), IL-5, and granulocyte macrophage colony
      stimulating factor (GM-CSF), IL-4 can be secreted by several cell types involved
      in allergic inflammatory reactions, and therefore can affect eosinophil function
      similarly. In this study, we investigated the presence of an IL-4 receptor (IL
      4R) on human eosinophils. When two different monoclonal antibodies (mAbs) against
      the IL-4R alpha-chain (IL-4Ralpha) were used, fluorescent-activated cell sorter
      analysis revealed the presence of an IL-4Ralpha on both eosinophils of normal
      donors and atopic dermatitis patients. In addition, the expression of the IL-2R
      gamma-chain, a functional component of the IL-4R in some cell types, was
      demonstrated. The IL-4Ralpha appeared to be expressed constitutively, and
      stimulation with cytokines IL-2, IL-3, IL-5, GM-CSF, and interferon-gamma did not
      further increase IL-4Ralpha expression. Evidence for an IL-4Ralpha was further
      substantiated by mRNA analysis. Both Northern blot analysis and reverse
      transcriptase/polymerase chain reaction revealed the presence of mRNA for the IL
      4Ralpha in eosinophils from normal individuals and AD patients. Furthermore, we
      demonstrated that both IL-4 and IL-13 were capable of inducing PI-3 kinase
      activity in human eosinophils. Because this activation could be inhibited by an
      IL-4Ralpha mAb, we conclude that both cytokines can activate human eosinophils
      through binding to a receptor complex comprising the IL-4Ralpha and-yet to be
      identified-associated proteins. In addition, the involvement of IL-4 in
      functional responses was studied. IL-4 appeared to "prime" eosinophils to respond
      chemotactically toward regulated on activation, normal T cells expressed and
      secreted, but did not affect platelet-activating factor-induced chemotaxis. Taken
      together, these data show the presence of a functional IL-4R on human
      eosinophils.

PMID- 9761769
TI  - http://www.fasebj.org 

PMID- 9761768
TI  - Surfactant protein-A-deficient mice are susceptible to Pseudomonas aeruginosa
      infection.
AB  - To determine the role of surfactant protein-A (SP-A) in host defense, the murine
      SP-A locus was targeted by homologous recombination to produce mice lacking SP-A.
      SP-A-/- and wild-type mice were infected with mucoid Pseudomonas aeruginosa by
      intratracheal instillation. Pulmonary bacterial loads were greater in SP-A-/-
      than in wild-type mice, with increased numbers of mucoid P. aeruginosa in lung
      homogenates at 6 and 24 h after infection. Pulmonary infiltration with
      polymorphonuclear leukocytes (PMN) was similar in both groups; however, an
      earlier influx of PMN into the lung occurred in the SP-A-/- mice. The number of
      bacteria phagocytosed by alveolar macrophages was decreased in the SP-A-/- mice
      at 1 h after infection. Superoxide-radical generation by PMN was similar for the
      SP-A-/- and wild-type mice, but nitrite levels were increased in SP-A-/- mice.
      Concentrations of tumor necrosis factor-alpha, interleukin-6, and macrophage
      inflammatory protein-2 (proinflammatory cytokines) were greater in
      bronchoalveolar lavage fluid at 2 h after infection in SP-A-/- mice. SP-A plays
      an important role in the pathogenesis of mucoid P. aeruginosa infection in the
      lung in vivo by enhancing macrophage phagocytosis and clearance of bacteria, and
      by modifying the inflammatory response.

PMID- 9761770
TI  - Molecular mimicry and immune-mediated diseases.
AB  - Molecular mimicry has been proposed as a pathogenetic mechanism for autoimmune
      disease, as well as a probe useful in uncovering its etiologic agents. The
      hypothesis is based in part on the abundant epidemiological, clinical, and
      experimental evidence of an association of infectious agents with autoimmune
      disease and observed cross-reactivity of immune reagents with host 'self'
      antigens and microbial determinants. For our purpose, molecular mimicry is
      defined as similar structures shared by molecules from dissimilar genes or by
      their protein products. Either the molecules' linear amino acid sequences or
      their conformational fits may be shared, even though their origins are as
      separate as, for example, a virus and a normal host self determinant. An immune
      response against the determinant shared by the host and virus can evoke a tissue
      specific immune response that is presumably capable of eliciting cell and tissue
      destruction. The probable mechanism is generation of cytotoxic cross-reactive
      effector lymphocytes or antibodies that recognize specific determinants on target
      cells. The induction of cross-reactivity does not require a replicating agent,
      and immune-mediated injury can occur after the immunogen has been removed a hit
      and-run event. Hence, the viral or microbial infection that initiates the
      autoimmune phenomenon may not be present by the time overt disease develops. By a
      complementary mechanism, the microbe can induce cellular injury and release self
      antigens, which generate immune responses that cross-react with additional but
      genetically distinct self antigens. In both scenarios, analysis of the T cells or
      antibodies specifically engaged in the autoimmune response and disease provides a
      fingerprint for uncovering the initiating infectious agent.

PMID- 9761771
TI  - Interactions between scatter factors and their receptors: hints for therapeutic
      applications.
AB  - The scatter factors, which include hepatocyte growth factor and macrophage
      stimulating protein, stand out from other cytokines because of their uncommon
      biological properties. In addition to promoting cell growth and protection from
      apoptosis, they are involved in the control of cell dissociation, migration into
      extracellular matrices, and a unique process of differentiation called 'branching
      morphogenesis'. Through the concerted regulation of these complex phenomena,
      scatter factors promote development, regeneration, and reconstruction of normal
      organ architecture. In transformed epithelia, scatter factors can mediate tumor
      invasive growth, a harmful feature of neoplastic progression in which cancer
      cells invade surrounding tissues, penetrate across the vascular walls, and
      eventually disseminate throughout the body, giving rise to systemic metastases. A
      much-debated issue in basic biology, which has strong implications for
      experimental medicine, is how to dissociate the favorable effects of growth
      factors from their adverse ones. Accordingly, to find agonists or antagonists
      with potential therapeutic applications is a crucial undertaking for current
      research. Domain-mapping analyses of growth factor molecules can help to isolate
      specific structural requirements for the induction of selective biological
      effects. Based on the observation that certain growth factors must undergo
      posttranslational modifications to exert a full response, it is possible to
      interfere with their activation mechanisms to modulate their functions. Finally,
      the identification of cell type-specific coreceptors able to potentiate their
      activity allows drawing of a functional body map, where some organs or tissues
      may be more responsive than others to growth factors. This review is focused on
      how, and to what extent, scatter factors can behave 'well' or 'badly' according
      to their molecular structure, the way they are activated, and the way they
      interact with cell surface receptors and coreceptors.

PMID- 9761772
TI  - Cys-scanning mutagenesis: a novel approach to structure function relationships in
      polytopic membrane proteins.
AB  - The entire lactose permease of Escherichia coli, a polytopic membrane transport
      protein that catalyzes beta-galactoside/H+ symport, has been subjected to Cys
      scanning mutagenesis in order to determine which residues play an obligatory role
      in the mechanism and to create a library of mutants with a single-Cys residue at
      each position of the molecule for structure/function studies. Analysis of the
      mutants has led to the following: 1) only six amino acid side chains play an
      irreplaceable role in the transport mechanism; 2) positions where the reactivity
      of the Cys replacement is increased upon ligand binding are identified; 3)
      positions where the reactivity of the Cys replacement is decreased by ligand
      binding are identified; 4) helix packing, helix tilt, and ligand-induced
      conformational changes are determined by using the library of mutants in
      conjunction with a battery of site-directed techniques; 5) the permease is a
      highly flexible molecule; and 6) a working model that explains coupling between
      beta-galactoside and H+ translocation. structure-function relationships in
      polytopic membrane proteins.

PMID- 9761773
TI  - Tissue-specific effects of in vivo adenosine receptor blockade on glucose uptake
      in Zucker rats.
AB  - Previous studies have shown that treatment of obese Zucker rats with the
      adenosine receptor antagonist 1,3-dipropyl-8-(p-acrylic) phenyl xanthine
      (BWA1433) improves intraperitoneal glucose tolerance. In this study, a euglycemic
      hyperinsulinemic clamp was performed on obese (fa/fa) and lean (Fa/fa) Zucker
      rats that had been treated orally with BWA1433 or vehicle for 1 wk. A constant
      infusion of [3H]glucose was initiated in fasted animals to measure basal whole
      body glucose kinetics. No differences in glucose concentration or rates of
      glucose production/disappearance were observed between lean or obese animals with
      or without BWA1433. During the euglycemic hyperinsulinemic clamp, whole body
      glucose disposal in obese Zucker rats was only 22% of that observed in lean
      animals. BWA1433 treatment increased glucose disposal by 88% in obese Zucker
      rats. At the end of the clamp, [14C]-2-deoxyglucose was injected to determine
      tissue-specific differences in glucose uptake. Gastrocnemius, soleus, heart, and
      liver of untreated obese animals had significantly lower glucose uptake than lean
      controls under hyperinsulinemic conditions. BWA1433 treatment of obese animals
      increased glucose uptake in gastrocnemius and soleus muscles by 44 and 47%,
      respectively. Conversely, BWA1433 treatment decreased glucose uptake in adipose
      tissue by 54 and 49% in obese and lean Zucker rats, respectively. In summary,
      BWA1433 improves glucose tolerance by increasing glucose uptake in skeletal
      muscle while decreasing glucose uptake by adipose tissue. This study suggests
      that insulin resistance in obese Zucker rats is tissue specific and that
      signaling from adenosine receptors may be a factor contributing to tissue
      specific insulin resistance.

PMID- 9761774
TI  - Characterization of human PLD2 and the analysis of PLD isoform splice variants.
AB  - Phospholipase D (PLD) cleaves phosphatidylcholine in response to a variety of
      cell stimuli to release phosphatidic acid, which is associated with a number of
      cellular responses including regulated secretion, mitogenesis, and cytoskeletal
      changes. Recent advances in this field include the reports of cDNA sequences for
      two mammalian PLD isoforms: human PLD1 and rodent PLD2. We report the
      characterization of cDNA encoding human PLD2. In these experiments, we uncovered
      alternate splice variants of both human isoforms and evaluated the relative
      abundance of these messages by reverse transcriptase polymerase chain reaction,
      thereby indicating the physiologically relevant forms. Further, Northern
      hybridization experiments defined the tissue distribution of the human PLD
      messages. Human PLD1 does not appear to be an abundant message in any tissue
      tested whereas levels of human PLD2 mRNA apparently were higher and more
      variable. The specific activity and regulation of recombinant human PLD2 are
      indistinguishable from that of recombinant mouse PLD2. Analysis of the amino acid
      sequences of both human isoforms revealed important putative Pleckstrin homology
      domains and identified additional members of the PLD gene family that help to
      delimit the catalytic domain. The presence of Pleckstrin homology domains in the
      PLDs resolves several contradictory observations regarding PLD regulation and the
      domain structure of the proteins.

PMID- 9761775
TI  - The amino acid transport system y+L/4F2hc is a heteromultimeric complex.
AB  - 4F2hc is an almost ubiquitous transmembrane protein in mammalian cells; upon
      expression in Xenopus laevis oocytes, it induces amino acid transport with
      characteristics of system y+L. Indirect evidence fostered speculation that
      function requires the association of 4F2hc with another protein endogenous to
      oocytes and native tissues. We show that expression of system y+L-like amino acid
      transport activity by 4F2hc in oocytes is limited by an endogenous factor and
      that direct covalent modification of external cysteine residue(s) of an oocyte
      membrane protein blocks system y+L/4F2hc transport activity, based on the
      following. 1) Induction of system y+L-like activity saturates at very low doses
      of human 4F2hc cRNA (0.1 ng/oocyte). This saturation occurs with very low
      expression of 4F2hc at the oocyte surface, and further increased expression of
      the protein at the cell surface does not result in higher induction of system y+L
      like activity. 2) Human 4F2hc contains only two cysteine residues (C109 and
      C330). We mutated these residues, singly and in combination, to serine (C109S;
      CS1, C330S; CS2 and C109S-C330S, Cys-less). Mutation CS2 had no effect on the
      expressed system y+L-like transport activity, whereas C109S-containing mutants
      (CS1 and Cys-less) retained only partial y+L-like transport activity (30 to 50%
      of wild type). 3) Hg2+, the organic mercury compounds pCMB, and the membrane
      impermeant pCMBS almost completely inactivated system y+L-like induced by human
      4F2hc wild type and all the mutants studied. This was reversed by ss
      mercaptoethanol, indicating that external cysteine residue(s) are the target of
      this inactivation. 4) Sensitivity to Hg2+ inactivation is increased by
      pretreatment of oocytes with ss-mercaptoethanol or in the C109S-containing
      mutants (CS1 and Cys-less). The increased Hg2+ reactivity of C109S-containing
      mutants supports the possibility that C109 may be linked by a disulfide bond to
      the Hg2+-targeted cysteine residue of the associated protein. These results
      indicate that 4F2hc is intimately associated with a membrane oocyte protein for
      the expression of system y+L amino acid transport activity. To our knowledge,
      this is the first direct evidence for a heteromultimeric protein structure of an
      organic solute carrier in mammals.

PMID- 9761776
TI  - In vitro reconstruction of a human capillary-like network in a tissue-engineered
      skin equivalent.
AB  - For patients with extensive burns, wound coverage with an autologous in vitro
      reconstructed skin made of both dermis and epidermis should be the best
      alternative to split-thickness graft. Unfortunately, various obstacles have
      delayed the widespread use of composite skin substitutes. Insufficient
      vascularization has been proposed as the most likely reason for their unreliable
      survival. Our purpose was to develop a vascular-like network inside tissue
      engineered skin in order to improve graft vascularization. To reach this aim, we
      fabricated a collagen biopolymer in which three human cell types keratinocytes,
      dermal fibroblasts, and umbilical vein endothelial cells were cocultured. We
      demonstrated that the endothelialized skin equivalent (ESE) promoted spontaneous
      formation of capillary-like structures in a highly differentiated extracellular
      matrix. Immunohistochemical analysis and transmission electron microscopy of the
      ESE showed characteristics associated with the microvasculature in vivo (von
      Willebrand factor, Weibel-Palade bodies, basement membrane material, and
      intercellular junctions). We have developed the first endothelialized human
      tissue-engineered skin in which a network of capillary-like tubes is formed. The
      transplantation of this ESE on human should accelerate graft revascularization by
      inosculation of its preexisting capillary-like network with the patient's own
      blood vessels, as it is observed with autografts. In addition, the ESE turns out
      to be a promising in vitro angiogenesis model.

PMID- 9761777
TI  - Rapid insulinotropic effect of 17beta-estradiol via a plasma membrane receptor.
AB  - Impaired insulin secretion is a hallmark in both type I and type II diabetic
      individuals. Whereas type I (insulin-dependent diabetes mellitus) implies ss-cell
      destruction, type II (non-insulin dependent diabetes mellitus), responsible for
      75% of diabetic syndromes, involves diminished glucose-dependent secretion of
      insulin from pancreatic beta-cells. Although a clear demonstration of a direct
      effect of 17beta-estradiol on the pancreatic ss-cell is lacking, an in vivo
      insulinotropic effect has been suggested. In this report we describe the effects
      of 17beta-estradiol in mouse pancreatic ss-cells. 17beta-Estradiol, at
      physiological concentrations, closes K(ATP) channels, which are also targets for
      antidiabetic sulfonylureas, in a rapid and reversible manner. Furthermore, in
      synergy with glucose, 17beta-estradiol depolarizes the plasma membrane, eliciting
      electrical activity and intracellular calcium signals, which in turn enhance
      insulin secretion. These effects occur through a receptor located at the plasma
      membrane, distinct from the classic cytosolic estrogen receptor. Specific
      competitive binding and localization of 17beta-estradiol receptors at the plasma
      membrane was demonstrated using confocal reflective microscopy and
      immunocytochemistry. Gaining deeper knowledge of the effect induced by 17beta
      estradiol may be important in order to better understand the hormonal regulation
      of insulin secretion and for the treatment of NIDDM. receptor.

PMID- 9761778
TI  - Targeting of gliadin peptides, CD8, alpha/beta-TCR, and gamma/delta-TCR to Golgi
      complexes and vacuoles within celiac disease enterocytes.
AB  - Celiac disease (CD) is characterized by autodestruction of enterocytes after
      exposure of genetically susceptible individuals to dietary gluten. To define the
      transport pathways of proteins involved in the celiac immune response, we wished
      to determine the subcellular compartments of the intestinal mucosa where wheat
      gliadin peptides colocalize with receptors of T lymphocytes, including alpha/beta
      TCR, gamma/delta-TCR, and CD8. Semithin and ultrathin frozen section of jejunal
      biopsies from CD patients and controls were used to perform immunofluorescence
      and immunogold labeling as well as in situ hybridization experiments. In patients
      with active CD, we detected gliadin peptides in vacuoles and Golgi complexes of
      enterocytes. CD8, alpha/beta-TCR, and gamma/delta-TCR were found in vacuoles and
      Golgi complexes within these gliadin-containing enterocytes in addition to the
      surface of intraepithelial and mucosal T lymphocytes. In contrast, we observed
      that the localization of CD4, CD3, T cell-restricted intracellular antigen (TIA),
      and leukocyte common antigen (LCA) was restricted to lymphocytes in CD patients.
      We further detected labeling signals for gliadin peptides, CD8, alpha/beta-TCR,
      and gamma/delta-TCR at the basal membrane of enterocytes that were interdigitated
      by extensions of lymphocytes. In situ hybridization experiments revealed that CD8
      and gamma/delta-TCR were not expressed by CD enterocytes. We conclude that CD8,
      alpha/beta-TCR, and gamma/delta-TCR are targeted to Golgi complexes and vacuoles
      of small intestinal enterocytes in active CD. The observed process may be
      involved in the pathogenesis of CD enterocytes. We propose a mechanism for the
      uptake of CD8, alpha/beta-TCR, and gamma/delta-TCR by the basolateral membrane of
      small intestinal enterocytes.

PMID- 9761779
TI  - Testosterone mediates expression of the selenoprotein PHGPx by induction of
      spermatogenesis and not by direct transcriptional gene activation.
AB  - Selenium deficiency is known to be associated with male infertility, and the
      selenoprotein PHGPx has been shown to increase in rat testis after puberty and to
      depend on gonadotropin stimulation in hypophysectomized rats [Roveri et al.
      (1992) J. Biol. Chem. 267, 6142 6146]. Exposure of decapsulated whole testis,
      however, failed to reveal any transcriptional activation or inhibition of the
      PHGPx gene by testosterone, human chorionic gonadotropin, or forskolin.
      Nevertheless, it was verified that the specific activity of PHGPx in testis, but
      not of cGPx, correlated with sexual maturation. Leydig cell destruction in vivo
      by ethane dimethane sulfonate (EDS) resulted in a delayed decrease in PHGPx
      activity and mRNA that could be completely prevented by testosterone
      substitution. cGPx transiently increased upon EDS treatment, probably as a result
      of reactive macrophage augmentation. In situ mRNA hybridization studies
      demonstrated an uncharacteristic low level of cGPx transcription in testis,
      whereas PHGPx mRNA was abundantly and preferentially expressed in round
      spermatids. The data show that the age or gonadotropin-dependent expression of
      PHGPx in testis does not result from direct transcriptional gene activation by
      testosterone, but is due to differentiation stage-specific expression in late
      spermatids, which are under the control of Leydig cell-derived testosterone. The
      striking burst of PHGPx expression at the transition of round to elongated
      spermatids suggests an involvement of this selenoprotein in sperm maturation.

PMID- 9761780
TI  - Induction of the stress response with prostaglandin A1 increases I-kappaBalpha
      gene expression.
AB  - I-kappaBalpha is an intracellular protein that functions as a primary inhibitor
      of the proinflammatory transcription factor NF-kappaB. Induction of the stress
      response with heat shock was previously demonstrated to induce I-kappaBalpha gene
      expression. Because the stress response can also be induced by nonthermal
      stimuli, we determined whether induction of the stress response with
      prostaglandin A1 (PGA1) would induce I-kappaBalpha gene expression. Treatment of
      human bronchial epithelium (BEAS-2B cells) with PGA1 induced nuclear
      translocation of heat shock factor 1, thus confirming that PGA1 induces the
      stress response in BEAS-2B cells. Induction of the stress response with PGA1
      increased I-kappaBalpha mRNA expression in a time-dependent manner and increased
      I-kappaBalpha peptide expression. Transient transfection assays involving a human
      I-kappaBalpha promoter-luciferase reporter construct demonstrated that induction
      of the stress response with PGA1 activated the I-kappaBalpha promoter. Induction
      of the stress response with PGA1 and concomitant induction of I-kappaBalpha were
      associated with inhibition of TNF-alpha-mediated secretion of interleukin 8 and
      with inhibition of TNF-alpha-mediated nuclear translocation and activation of NF
      kappaB. These data demonstrate that induction of the stress response, by a
      nonthermal stimulus, increases I-kappaBalpha gene expression by a mechanism
      involving activation of the I-kappaBalpha promoter. Coupled with previous data
      demonstrating heat shock-mediated induction of I-kappaBalpha gene expression,
      these data suggest that I-kappaBalpha may be considered to be one of the stress
      proteins. The functional consequences of stress response-mediated I-kappaBalpha
      gene expression may involve attenuation of cellular proinflammatory responses.

PMID- 9761781
TI  - Divergent effects of exercise on metabolic and mitogenic signaling pathways in
      human skeletal muscle.
AB  - The molecular signaling mechanisms by which muscle contractions lead to changes
      in glucose metabolism and gene expression remain largely undefined. We assessed
      whether exercise activates MAP kinase proteins (ERK1/2, SEK1, and p38 MAP kinase)
      as well as Akt and PYK2 in skeletal muscle from healthy volunteers obtained
      during and after one-leg cycle ergometry at approximately 70% VO2max. Exercise
      led to a marked increase in ERK1/2 phosphorylation, which rapidly decreased to
      resting levels upon recovery. Exercise increased phosphorylation of SEK1 and p38
      MAP kinase to a lesser extent than ERK1/2. In contrast to ERK1/2, p38 MAP kinase
      phosphorylation was increased in nonexercised muscle upon cessation of exercise.
      Phosphorylation of the transcription factor CREB was increased in nonexercised
      muscle upon cessation of exercise. Exercise did not activate Akt or increase
      tyrosine phosphorylation of PYK2. Thus, exercise has divergent effects on
      parallel MAP kinase pathways, of which only p38 demonstrated a systemic response.
      However, our data do not support a role of Akt or PYK2 in exercise/contraction
      induced signaling in human skeletal. Activation of the different MAP kinase
      pathways by physical exercise appears to be important in the regulation of
      transcriptional events in skeletal muscle.

PMID- 9761782
TI  - The agouti gene product inhibits lipolysis in human adipocytes via a Ca2+
      dependent mechanism.
AB  - Overexpression of the murine agouti gene results in obesity. The human homologue
      of agouti is expressed primarily in human adipocytes, and we have shown
      recombinant agouti protein to increase adipocyte intracellular Ca2+([Ca2+]i) and
      thereby stimulate lipogenesis. However, since recent data demonstrate that
      increasing adipocyte [Ca2+]i may also inhibit lipolysis, we have investigated the
      role of agouti-induced [Ca2+]i increases in regulating lipolysis in human
      adipocytes. Short-term (1 h) exposure to recombinant agouti (100 nM) protein had
      no effect on basal lipolysis, although longer term treatment (24 h) caused a 60%
      decrease in basal lipolysis (P<0.0001). Short-term agouti treatment totally
      inhibited ACTH-induced lipolysis (P<0.05). Since melanocortin receptors (MCR) are
      involved in some actions of agouti, we next determined whether agouti's
      antilipolytic effect is exerted through competitive antagonism of the ACTH
      receptor (MCR-2). Forskolin (1 microM), an adenylate cyclase activator, induced a
      48% increase in lipolysis in human adipocytes (P<0.05); this effect was reversed
      by 100 nM agouti (P<005), demonstrating that the antilipolytic effect of agouti
      is distal to the ACTH receptor. To determine the role of [Ca2+]i in the
      antilipolytic effect of agouti, human adipocytes were treated with KCl or
      arginine vasopressin to stimulate voltage- and receptor-stimulated Ca2+ influx,
      respectively. Both agents caused inhibition of forskolin-induced lipolysis
      (P<0.005). Furthermore, agouti's antilipolytic effect was also blocked by the
      Ca2+ channel blocker nitrendipine. These data demonstrate that agouti exerts a
      potent antilipolytic effect in human adipocytes via a Ca2+-dependent mechanism.
      This effect, combined with agouti-induced lipogenesis, represents a coordinate
      control of adipocyte lipid metabolism that may contribute to an agouti-induced
      obesity syndrome.

PMID- 9761783
TI  - Oxidative DNA damage measured in human lymphocytes: large differences between
      sexes and between countries, and correlations with heart disease mortality rates.
AB  - The 'antioxidant hypothesis' proposes that vitamin C, vitamin E, carotenoids, and
      other antioxidants occurring in fruit and vegetables afford protection against
      heart disease and cancer by preventing oxidative damage to lipids and to DNA,
      respectively. To test elements of this hypothesis, we have measured blood levels
      of dietary antioxidants, and 8-oxodeoxyguanosine (8-oxo-dG) concentrations in
      lymphocyte DNA, in healthy men and women from five European countries: France,
      Ireland, The Netherlands, Spain, and the U.K. Volunteers, aged 25 45, all
      nonsmokers, gave blood samples before and after a 12-wk carotenoid
      supplementation regime. Vitamin C was measured in plasma and vitamin E and
      carotenoids were measured in serum by high-performance liquid chromatography
      (HPLC). 8-oxo-dG was assayed by HPLC (with coulometric detection) in DNA isolated
      from lymphocytes from the same blood samples. Mean values were calculated for
      groups of volunteers at each sampling time according to country, sex, and
      supplementation (between 9 and 24 individual samples contributing to each mean).
      We found that 8-oxo-dG levels in lymphocyte DNA vary significantly according to
      sex and country. A low mean 8-oxo-dG concentration is seen in DNA of women from
      all five countries, and of men from France and Spain. 8-oxo-dG is significantly
      higher (up to about threefold) in lymphocyte DNA from men in Ireland and the U.K.
      Oxidative DNA damage is not significantly affected by carotenoid supplementation;
      nor is there any association with mean baseline levels of antioxidants, which are
      generally similar in the five countries. The five countries sampled lie on an
      axis from northern to southern Europe with a steep gradient in terms of premature
      heart disease. There is a strong association between premature coronary heart
      disease mortality in men and the mean levels of 8-oxo-dG for the five countries
      (r = 0.95, P < 0.01). Women have low coronary heart disease mortality rates,
      which do not correlate with 8-oxo-dG. In terms of cancer deaths, only colorectal
      cancer in men shows a significant positive correlation (r = 0.91, P < 0.05), and
      stomach cancer in women is negatively correlated with DNA oxidation (r = -0.92, P
      = 0.01).

PMID- 9761784
TI  - Membrane-bound calmodulin in Xenopus laevis oocytes as a novel binding site for
      melatonin.
AB  - Melatonin has been suggested as a physiological antagonist of calmodulin. In this
      work, we have characterized melatonin binding sites in Xenopus laevis oocyte
      membranes. Binding of [125I]melatonin by X. laevis oocyte membranes fulfills all
      criteria for binding to a receptor site. Binding was dependent on time,
      temperature, and membrane concentration and was stable, reversible, saturable,
      and specific. The binding site was also pharmacologically characterized.
      Stoichiometric studies showed a high-affinity binding site with a Kd of 1.18 nM.
      These data are in close agreement with data obtained from kinetic studies
      (Kd=0.12 nM). In competition studies, we observed a low-affinity binding site
      (Kd=63.41 microM). Moreover, the binding site was characterized as calmodulin.
      Thus, binding was dependent on calcium and blocked by anti-CaM antibodies in a
      concentration-dependent manner. Calmodulin inhibitor chlorpromazine also
      inhibited binding of the tracer. From these results, it is suggested that
      membrane-bound calmodulin acts as a melatonin binding site in Xenopus laevis
      oocytes, where it might couple cellular activities to rhythmic circulating levels
      of melatonin. This hypothesis correlates with the previous findings describing
      melatonin as a physiological antagonist of calmodulin.

PMID- 9761785
TI  - Putative susceptibility markers of coronary artery disease: association between
      VDR genotype, smoking, and aromatic DNA adduct levels in human right atrial
      tissue.
AB  - Cancer and cardiovascular diseases share risk factors such as smoking, and the
      onset of both diseases have been suggested to have a common mechanistic basis.
      The binding of carcinogens to DNA (carcinogen-DNA adducts), genetic polymorphisms
      in carcinogen-detoxifying enzymes glutathione S-transferases (GSTs), and genetic
      polymorphisms in the vitamin D receptor (VDR) are among the candidates for
      modifiers of cancer risk. We determined whether these biomarkers could be related
      to individual characteristics of patients suffering from cardiovascular diseases.
      For that purpose, DNA from the right atrial appendage of 41 patients who
      underwent open heart surgery was analyzed for smoking-related DNA adducts and
      polymorphisms in GSTM1, GSTT1, and VDR genes. Statistical analysis was used to
      identify any patient's characteristics associated with these molecular markers.
      Our results showed that heart tissue of cigarette smokers contained a variety of
      aromatic DNA adducts in significantly elevated levels compared to ex-smokers
      (P<0.01) or nonsmokers (P<0.001). A linear relationship was observed between DNA
      adduct levels and daily cigarette smoking (rs=0.73; P=0.0003). Since cardiac
      myocytes are terminally differentiated cells that have lost their ability to
      divide and seemingly have limited DNA repair capacities, their levels might
      accumulate with time and thereby affect heart cell function or viability.
      Substantial interindividual differences between DNA adduct levels were observed,
      and persons with severe coronary artery disease (CAD), as assessed by coronary
      angiography, had higher DNA adduct levels than persons with no or mild CAD
      (P=0.04). As polymorphisms in GST genes have been shown to modulate DNA adduct
      levels and risk for lung cancer in smokers, we explored for the first time
      whether the GST polymorphisms could also explain deviating heart DNA adduct
      levels and CAD risk. However, no relation could be found between these
      covariants. In contrast, a VDR genotype, which has been associated with decreased
      serum levels of the active hormonal form of vitamin D and increased risk for
      certain cancers, seemed to be related to severity of CAD (P=0.025). Our findings
      support the hypothesis that smoking-related DNA damage may be involved in the
      onset of cardiovascular diseases and suggest that VDR genotype may be a useful
      susceptibility marker of CAD.

PMID- 9761787
TI  - Auxin signaling. Homing In with targeted genetics 

PMID- 9761786
TI  - In vitro modulation of primate coronary vascular muscle cell reactivity by
      ovarian steroid hormones.
AB  - Susceptibility to drug-induced coronary vasospasm in rhesus monkeys increases
      after removal of the ovaries and can be normalized by adding back physiological
      levels of estradiol-17ss (E2) and/or natural progesterone (P) in vivo as reported
      recently by our group. Furthermore, the reactivity status (Ca2+ and protein
      kinase C responses) of freshly isolated and primary culture coronary artery
      vascular muscle cells (VMC) mimic the intact coronary artery responses to 5-HT +
      U46619. Since coronary reactivity is maintained in the isolated VMC, we
      hypothesized that the reactivity state inherent in the VMC was modulated directly
      by ovarian steroids in vitro as in the whole animal. To test this hypothesis, we
      treated hyperreactive VMC from ovariectomized (ovx) monkeys in vitro with E2 or P
      and measured VMC reactivity to combined stimulation with 5-HT and U46619, as
      determined by the amplitude and especially the duration of intracellular Ca2+
      signals, as well as protein kinase C (PKC) activation/translocation. VMC were
      treated for 12 96 h with 3 100 pg/ml E2 (10 365 pM) and/or 0.3 3 ng/ml P (0.95
      9.5 nM). Hyperreactive responses to the combination of 5-HT and U46619 in
      untreated VMC were significantly and dose-dependently reduced by treatment in
      vitro with physiological levels of either E2 or P for at least 24 h. Both the
      early transient and late sustained increases in intracellular Ca2+ and PKC
      translocation were blunted, and the effects of 0.2 nM E2 and 3.2 nM P were
      specifically antagonized by the receptor blockers ICI 182,780 (200 nM) and RU486
      (15 nM), respectively. Antibodies to the estrogen receptor and progesterone
      receptor labeled nuclei in VMC, which were also positively labeled by a smooth
      muscle myosin heavy chain monoclonal antibody. These data indicate that natural
      ovarian steroids directly reduce hyperreactive 5-HT and thromboxane A2-stimulated
      Ca2+ and PKC responses of coronary artery VMC from surgically menopausal rhesus
      macaques. We hypothesize that vascular hyperreactivity, which may be a critical
      factor involved in the increased incidence of coronary artery vasospasm and
      ischemic heart disease in postmenopausal women, can be normalized by E2 and/or P
      through direct actions on coronary artery vascular muscle cells.

PMID- 9761788
TI  - Nodule parenchyma-specific expression of the sesbania rostrata early nodulin gene
      SrEnod2 is mediated by its 3' untranslated region 
AB  - The early nodulin Enod2 gene encodes a putative hydroxyproline-rich cell wall
      protein and is expressed exclusively in the nodule parenchyma cell layer. The
      latter finding suggests that the Enod2 protein may contribute to the special
      morphological features of the nodule parenchyma and to the creation of an oxygen
      diffusion barrier. The Enod2 gene of the stem-nodulating legume Sesbania rostrata
      (SrEnod2) is induced specifically in roots by the plant hormone cytokinin, and
      this induction occurs at a post-transcriptional level. Here, we characterize the
      cis determinant(s) in the SrEnod2 locus responsible for nodule parenchyma
      specific expression and show that the 3' untranslated region (UTR) of the SrEnod2
      gene is both required and sufficient for directing chimeric reporter gene
      expression in the nodule parenchyma of transgenic Lotus corniculatus plants.
      Moreover, we show that the SrEnod2 3' UTR does not act as a tissue-specific
      enhancer element. By conducting a detailed deletion analysis of the 5' and 3'
      SrEnod2 regions, we delimited the minimal promoter of the SrEnod2 gene, and it
      appears that the 5' flanking sequences are not essential for nodule parenchyma
      specific expression. This finding is in contrast with the report that the 5'
      upstream region of the soybean Enod2 gene directs nodule parenchyma-specific
      expression, indicating that different mechanisms may be involved in regulating
      the expression of these two genes. We definitively demonstrate that the cis
      element(s) for tissue-specific expression is located within the 3' UTR of a plant
      nuclear gene.

PMID- 9761789
TI  - Ribozymes targeted to stearoyl-ACP delta9 desaturase mRNA produce heritable
      increases of stearic acid in transgenic maize leaves.
AB  - Ribozymes are RNAs that can be designed to catalyze the specific cleavage or
      ligation of target RNAs. We have explored the possibility of using ribozymes in
      maize to downregulate the expression of the stearoyl-acyl carrier protein
      (Delta9) desaturase gene. Based on site accessibility and catalytic activity,
      several ribozyme constructs were designed and transformed into regenerable maize
      lines. One of these constructs, a multimer hammerhead ribozyme linked to a
      selectable marker gene, was shown to increase leaf stearate in two of 13 maize
      lines. There were concomitant decreases in Delta9 desaturase mRNA and protein.
      The plants with the altered stearate phenotype were shown to express ribozyme
      RNA. The ribozyme-mediated trait was heritable, as evidenced by stearate
      increases in the leaves of the R1 plants derived from a high-stearate line. The
      increase in stearate correlated with the presence of the ribozyme gene. A
      catalytically inactive version of this ribozyme did not produce any significant
      effect in transgenic maize. This is evidence that ribozymes can be used to
      modulate the expression of endogenous genes in maize.

PMID- 9761790
TI  - Involvement of an ABC transporter in a developmental pathway regulating hypocotyl
      cell elongation in the light 
AB  - In the dark, plant seedlings follow the skotomorphogenetic developmental program,
      which results in hypocotyl cell elongation. When the seedlings are exposed to
      light, a switch to photomorphogenetic development occurs, and hypocotyl cell
      elongation is inhibited. We have manipulated the expression of the AtPGP1 (for
      Arabidopsis thaliana P glycoprotein1) gene in transgenic Arabidopsis plants by
      using sense and antisense constructs. We show that within a certain light fluence
      rate window, overexpression of the AtPGP1 gene under the control of the
      cauliflower mosaic virus 35S promoter causes plants to develop longer hypocotyls,
      whereas expression of the gene in antisense orientation results in hypocotyls
      shorter than those occurring in the wild type. In the dark, hypocotyls of
      transgenic and wild-type plants are indistinguishable. Because the AtPGP1 gene
      encodes a member of the superfamily of ATP binding cassette-containing (ABC)
      transporters, these results imply that a transport process is involved in a
      hypocotyl cell elongation pathway active in the light. The AtPGP1 transporter is
      localized in the plasmalemma, as indicated by immunohistochemical techniques and
      biochemical membrane separation methods. Analysis of the AtPGP1 expression
      pattern by using reporter gene constructs and in situ hybridization shows that in
      wild-type seedlings, AtPGP1 is expressed in both the root and shoot apices.

PMID- 9761791
TI  - The plant U1 small nuclear ribonucleoprotein particle 70K protein interacts with
      two novel serine/arginine-rich proteins.
AB  - The U1 small nuclear ribonucleoprotein particle (U1 snRNP) 70K protein (U1-70K),
      one of the three U1 snRNP-specific proteins, is implicated in basic and
      alternative splicing of nuclear pre-mRNAs. We have used the Arabidopsis U1-70K in
      the yeast two-hybrid system to isolate cDNAs encoding proteins that interact with
      it. This screening has resulted in the isolation of two novel plant
      serine/arginine-rich (SR) proteins, SRZ-22 and SRZ-21 (SRZ proteins). Neither the
      N-terminal region nor the arginine-rich C-terminal region of U1-70K alone
      interact with the SRZ proteins. The interaction of U1-70K with the SRZ proteins
      is confirmed further in vitro using a blot overlay assay. The plant SRZ proteins
      are highly similar to each other and contain conserved modular domains unique to
      different groups of splicing factors in the SR family of proteins. SRZ proteins
      are similar to human 9G8 splicing factor because they contain a zinc knuckle,
      precipitate with 65% ammonium sulfate, and cross-react with the 9G8 monoclonal
      antibody. However, unlike the 9G8 splicing factor, SRZ proteins contain a glycine
      hinge, a unique feature in other splicing factors (SC35 and ASF/SF2), located
      between the RNA binding domain and the zinc knuckle. SRZ-22 and SRZ-21 are
      encoded by two distinct genes and are expressed in all tissues tested with varied
      levels of expression. Our results suggest that the plant SRZ proteins represent a
      new group of SR proteins. The interaction of plant U1-70K with the SRZ proteins
      may account for some differences in pre-mRNA splicing between plants and animals.

PMID- 9761792
TI  - age Mutants of Arabidopsis exhibit altered auxin-regulated gene expression.
AB  - An Arabidopsis transgenic line was constructed expressing beta-glucuronidase
      (GUS) via the auxin-responsive domains (AuxRDs) A and B (BA-GUS) of the PS-IAA4/5
      gene in an indoleacetic acid (IAA)-dependent fashion. GUS expression was
      preferentially enhanced in the root elongation zone after treatment of young
      seedlings with 10(-7) M IAA. Expression of the BA-GUS gene in the axr1, axr4, and
      aux1 mutants required 10- to 100-fold higher auxin concentration than that in the
      wild-type background. GUS expression was nil in the axr 2 and axr 3 mutants. The
      transgene was used to isolate mutants exhibiting altered auxin-responsive gene
      expression (age). Two mutants, age1 and age2, were isolated and characterized.
      age1 showed enhanced sensitivity to IAA, with strong GUS expression localized in
      the root elongation zone in the presence of 10(-8) M IAA. In contrast, age2
      exhibited ectopic GUS expression associated with the root vascular tissue, even
      in the absence of exogenous IAA. Morphological and molecular analyses indicated
      that the age1 and age2 alleles are involved in the regulation of gene expression
      in response to IAA.

PMID- 9761793
TI  - Photoinduction of flower identity in vegetatively biased primordia.
AB  - Far-red light and long photoperiods promote flowering in Arabidopsis. We report
      here that when 30-day-old vegetative plants were induced with a continuous light
      treatment enriched in far-red light, flowers developed directly from previously
      initiated primordia. Specifically, plants induced with our continuous
      incandescent-enriched (CI) treatment produced an average of two primary-axis
      nodes with a leaf/flower phenotype, indicating that approximately two
      leaf/paraclade primordia per plant produced an individual flower from tissue that
      typically would differentiate into a paraclade (secondary inflorescence). Assays
      for APETALA1::beta-glucuronidase activity during the CI photoinduction treatment
      indicated that the floral meristem identity gene APETALA1 was transcriptionally
      activated in primordia with a leaf/paraclade bias and in primordia committed to
      leaf/paraclade development. APETALA1::beta-glucuronidase activity levels were
      initially highest in young primordia but were not correlated strictly with
      primordium fate. These results indicate that primordium fate can be modified
      after primordium initiation and that developing primordia respond quantitatively
      to floral induction signals.

PMID- 9761794
TI  - The Arabidopsis DIMINUTO/DWARF1 gene encodes a protein involved in steroid
      synthesis.
AB  - We have identified the function of the Arabidopsis DIMINUTO/DWARF1 (DIM/DWF1)
      gene by analyzing the dim mutant, a severe dwarf with greatly reduced fertility.
      Both the mutant phenotype and gene expression could be rescued by the addition of
      exogenous brassinolide. Analysis of endogenous sterols demonstrated that dim
      accumulates 24-methylenecholesterol but is deficient in campesterol, an early
      precursor of brassinolide. In addition, we show that dim is deficient in
      brassinosteroids as well. Feeding experiments using deuterium-labeled 24
      methylenecholesterol and 24-methyldesmosterol confirmed that DIM/DWF1 is involved
      in both the isomerization and reduction of the Delta24(28) bond. This conversion
      is not required in cholesterol biosynthesis in animals but is a key step in the
      biosynthesis of plant sterols. Transient expression of a green fluorescent
      protein-DIM/DWF1 fusion protein and biochemical experiments showed that DIM/DWF1
      is an integral membrane protein that most probably is associated with the
      endoplasmic reticulum.

PMID- 9761795
TI  - Developmental control of telomere lengths and telomerase activity in plants.
AB  - Telomere lengths and telomerase activity were studied during the development of a
      model dioecious plant, Melandrium album (syn Silene latifolia). Telomeric DNA
      consisted of Arabidopsis-type TTTAGGG tandem repeats. The terminal positions of
      these repeats were confirmed by both Bal31 exonuclease degradation and in situ
      hybridization. Analysis of terminal restriction fragments in different tissues
      and ontogenetic stages showed that telomere lengths are stabilized precisely and
      do not change during plant growth and development. Telomerase activity tested by
      using a semiquantitative telomerase repeat amplification protocol correlated with
      cell proliferation in the tissues analyzed. Highest activity was found in
      germinating seedlings and root tips, whereas we observed a 100-fold decrease in
      telomerase activity in leaves and no activity in quiescent seeds. Telomerase also
      was found in mature pollen grains. Telomerase activity in tissues containing
      dividing cells and telomere length stability during development suggest their
      precise control during plant ontogenesis; however, the telomere length regulation
      mechanism could be unbalanced during in vitro dedifferentiation.

PMID- 9761796
TI  - A mutant of Arabidopsis lacking a chloroplastic isoamylase accumulates both
      starch and phytoglycogen.
AB  - In this study, our goal was to evaluate the role of starch debranching enzymes in
      the determination of the structure of amylopectin. We screened mutant populations
      of Arabidopsis for plants with alterations in the structure of leaf starch by
      using iodine staining. The leaves of two mutant lines stained reddish brown,
      whereas wild-type leaves stained brownish black, indicating that a more highly
      branched polyglucan than amylopectin was present. The mutants were allelic, and
      the mutation mapped to position 18.8 on chromosome 1. One mutant line lacked the
      transcript for a gene with sequence similarity to higher plant debranching
      enzymes, and both mutants lacked a chloroplastic starch-hydrolyzing enzyme. This
      enzyme was identified as a debranching enzyme of the isoamylase type. The loss of
      this isoamylase resulted in a 90% reduction in the accumulation of starch in this
      mutant line when compared with the wild type and in the accumulation of the
      highly branched water-soluble polysaccharide phytoglycogen. Both normal starch
      and phytoglycogen accumulated simultaneously in the same chloroplasts in the
      mutant lines, suggesting that isoamylase has an indirect rather than a direct
      role in determining amylopectin structure.

PMID- 9761797
TI  - rbcL Transcript levels in tobacco plastids are independent of light: reduced dark
      transcription rate is compensated by increased mRNA stability.
AB  - The plastid rbcL gene, encoding the large subunit of ribulose-1, 5-bisphosphate
      carboxylase, in higher plants is transcribed from a sigma70 promoter by the
      eubacterial-type RNA polymerase. To identify regulatory elements outside of the
      rbcL -10/-35 promoter core, we constructed transplastomic tobacco plants with
      uidA reporter genes expressed from rbcL promoter derivatives. Promoter activity
      was characterized by measuring steady state levels of uidA mRNA on RNA gel blots
      and by measuring promoter strength in run-on transcription assays. We report here
      that the rbcL core promoter is sufficient to obtain wild-type rates of
      transcription. Furthermore, the rates of transcription were up to 10-fold higher
      in light-grown leaves than in dark-adapted plants. Although the rates of
      transcription were lower in the dark, rbcL mRNA accumulated to similar levels in
      light-grown and dark-adapted leaves. Accumulation of uidA mRNA from most rbcL
      promoter deletion derivatives directly reflected the relative rates of
      transcription: high in the light-grown and low in the dark-adapted leaves.
      However, uidA mRNA accumulated to high levels in a light-independent fashion as
      long as a segment encoding a stem-loop structure in the 5' untranslated region
      was included in the promoter construct. This finding indicates that lower rates
      of rbcL transcription in the dark are compensated by increased mRNA stability.

PMID- 9761798
TI  - Identification of residues in a hydrophilic loop of the Papaver rhoeas S protein
      that play a crucial role in recognition of incompatible pollen.
AB  - The self-incompatibility response involves S allele-specific recognition between
      stigmatic S proteins and incompatible pollen. This response results in pollen
      inhibition. Defining the amino acid residues within the stigmatic S proteins that
      participate in S allele-specific inhibition of incompatible pollen is essential
      for the elucidation of the molecular basis of the self-incompatibility response.
      We have constructed mutant derivatives of the S1 protein from Papaver rhoeas by
      using site-directed mutagenesis and have tested their biological activity. This
      has enabled us to identify amino acid residues in the stigmatic S proteins of P.
      rhoeas that are required for S-specific inhibition of incompatible pollen. We
      report here the identification of several amino acid residues in the predicted
      hydrophilic loop 6 of the P. rhoeas stigmatic S1 protein that are involved in the
      inhibition of S1 pollen. Mutation of the only hypervariable amino acid, which is
      situated in this loop, resulted in the complete loss of ability of the S protein
      to inhibit S1 pollen. This clearly demonstrates that this residue plays a crucial
      role in pollen recognition and may also participate in defining allelic
      specificity. We have also established the importance of highly conserved amino
      acids adjacent to this hypervariable site. Our studies demonstrate that both
      variable and conserved amino acids in the region of the S protein corresponding
      to surface loop 6 are key elements that play a role in the recognition and
      inhibition of incompatible pollen in the pollen-pistil self-incompatibility
      reaction.

PMID- 9761799
TI  - Inefficient reinitiation is responsible for upstream open reading frame-mediated
      translational repression of the maize R gene.
AB  - Maize R genes encode a small family of transcriptional activators of several
      structural genes in the anthocyanin biosynthetic pathway. The 5' leader region of
      most R genes contains a 38-codon upstream open reading frame (uORF) that
      previously was shown to be responsible for the repression of downstream gene
      expression in a transient transformation assay. In this study, we report that the
      5' leader also can repress translation of the downstream luciferase gene both in
      the rabbit reticulocyte translation system and in transgenic rice plants. The
      ability to visualize the uORF peptide after in vitro translation permits
      quantification of both products of dicistronic mRNAs. Similarly, the construction
      of transgenic rice plants expressing wild-type and mutant constructs permits the
      quantification and correlation of steady state mRNA levels and reporter gene
      activities. Using these assays, we demonstrate directly that translation of the
      uORF is required for repression, that increasing translation of the uORF peptide
      decreases downstream gene expression, and that repression is unaffected by either
      subtle or gross changes in the uORF peptide. Rather, we find that ribosomes that
      translate the uORF reinitiate inefficiently and that the intercistronic sequence
      downstream of the uORF mediates this effect.

PMID- 9761800
TI  - Arabidopsis mutants impaired in cosuppression.
AB  - Post-transcriptional gene silencing (cosuppression) results in the degradation of
      RNA after transcription. A transgenic Arabidopsis line showing post
      transcriptional silencing of a 35S-uidA transgene and uidA-specific methylation
      was mutagenized using ethyl methanesulfonate. Six independent plants were
      isolated in which uidA mRNA accumulation and beta-glucuronidase activity were
      increased up to 3500-fold, whereas the transcription rate of the 35S-uidA
      transgene was increased only up to threefold. These plants each carried a
      recessive monogenic mutation that is responsible for the release of silencing.
      These mutations defined two genetic loci, called sgs1 and sgs2 (for suppressor of
      gene silencing). Transgene methylation was distinctly modified in sgs1 and sgs2
      mutants. However, methylation of centromeric repeats was not affected, indicating
      that sgs mutants differ from ddm (for decrease in DNA methylation) and som (for
      somniferous) mutants. Indeed, unlike ddm and som mutations, sgs mutations were
      not able to release transcriptional silencing of a 35S-hpt transgene. Conversely,
      both sgs1 and sgs2 mutations were able to release cosuppression of host Nia genes
      and 35S-Nia2 transgenes. These results therefore indicate that sgs mutations act
      in trans to impede specifically transgene-induced post-transcriptional gene
      silencing.

PMID- 9761801
TI  - Targeting of active sialyltransferase to the plant Golgi apparatus.
AB  - Glycosyltransferases in the Golgi apparatus synthesize cell wall polysaccharides
      and elaborate the complex glycans of glycoproteins. To investigate the targeting
      of this type of enzyme to plant Golgi compartments, we generated transgenic
      Arabidopsis plants expressing alpha-2,6-sialyltransferase, a glycosyltransferase
      of the mammalian trans-Golgi cisternae and the trans-Golgi network. Biochemical
      analysis as well as immunolight and immunoelectron microscopy of these plants
      indicate that the protein is targeted specifically to the Golgi apparatus.
      Moreover, the protein is predominantly localized to the cisternae and membranes
      of the trans side of the organelle. When supplied with the appropriate
      substrates, the enzyme has significant alpha-2,6-sialyltransferase activity.
      These results indicate a conservation of glycosyltransferase targeting mechanisms
      between plant and mammalian cells and also demonstrate that glycosyltransferases
      can be subcompartmentalized to specific cisternae of the plant Golgi apparatus.

PMID- 9761802
TI  - A comparison of active and simulated chiropractic manipulation as adjunctive
      treatment for childhood asthma.
AB  - BACKGROUND: Chiropractic spinal manipulation has been reported to be of benefit
      in nonmusculoskeletal conditions, including asthma. METHODS: We conducted a
      randomized, controlled trial of chiropractic spinal manipulation for children
      with mild or moderate asthma. After a three-week base-line evaluation period, 91
      children who had continuing symptoms of asthma despite usual medical therapy were
      randomly assigned to receive either active or simulated chiropractic manipulation
      for four months. None had previously received chiropractic care. Each subject was
      treated by 1 of 11 participating chiropractors, selected by the family according
      to location. The primary outcome measure was the change from base line in the
      peak expiratory flow, measured in the morning, before the use of a
      bronchodilator, at two and four months. Except for the treating chiropractor and
      one investigator (who was not involved in assessing outcomes), all participants
      remained fully blinded to treatment assignment throughout the study. RESULTS:
      Eighty children (38 in the active-treatment group and 42 in the simulated
      treatment group) had outcome data that could be evaluated. There were small
      increases (7 to 12 liters per minute) in peak expiratory flow in the morning and
      the evening in both treatment groups, with no significant differences between the
      groups in the degree of change from base line (morning peak expiratory flow,
      P=0.49 at two months and P=0.82 at four months). Symptoms of asthma and use of 3
      agonists decreased and the quality of life increased in both groups, with no
      significant differences between the groups. There were no significant changes in
      spirometric measurements or airway responsiveness. CONCLUSIONS: In children with
      mild or moderate asthma, the addition of chiropractic spinal manipulation to
      usual medical care provided no benefit.

PMID- 9761803
TI  - A comparison of physical therapy, chiropractic manipulation, and provision of an
      educational booklet for the treatment of patients with low back pain.
AB  - BACKGROUND AND METHODS: There are few data on the relative effectiveness and
      costs of treatments for low back pain. We randomly assigned 321 adults with low
      back pain that persisted for seven days after a primary care visit to the
      McKenzie method of physical therapy, chiropractic manipulation, or a minimal
      intervention (provision of an educational booklet). Patients with sciatica were
      excluded. Physical therapy or chiropractic manipulation was provided for one
      month (the number of visits was determined by the practitioner but was limited to
      a maximum of nine); patients were followed for a total of two years. The
      bothersomeness of symptoms was measured on an 11-point scale, and the level of
      dysfunction was measured on the 24-point Roland Disability Scale. RESULTS: After
      adjustment for base-line differences, the chiropractic group had less severe
      symptoms than the booklet group at four weeks (P=0.02), and there was a trend
      toward less severe symptoms in the physical therapy group (P=0.06). However,
      these differences were small and not significant after transformations of the
      data to adjust for their non-normal distribution. Differences in the extent of
      dysfunction among the groups were small and approached significance only at one
      year, with greater dysfunction in the booklet group than in the other two groups
      (P=0.05). For all outcomes, there were no significant differences between the
      physical-therapy and chiropractic groups and no significant differences among the
      groups in the numbers of days of reduced activity or missed work or in
      recurrences of back pain. About 75 percent of the subjects in the therapy groups
      rated their care as very good or excellent, as compared with about 30 percent of
      the subjects in the booklet group (P<0.001). Over a two-year period, the mean
      costs of care were $437 for the physical-therapy group, $429 for the chiropractic
      group, and $153 for the booklet group. CONCLUSIONS: For patients with low back
      pain, the McKenzie method of physical therapy and chiropractic manipulation had
      similar effects and costs, and patients receiving these treatments had only
      marginally better outcomes than those receiving the minimal intervention of an
      educational booklet. Whether the limited benefits of these treatments are worth
      the additional costs is open to question.

PMID- 9761804
TI  - Effect of nebulized ipratropium on the hospitalization rates of children with
      asthma.
AB  - BACKGROUND: Anticholinergic medications such as ipratropium improve the pulmonary
      function of patients with acute exacerbations of asthma, but their effect on
      hospitalization rates is uncertain. METHODS: We conducted a randomized, double
      blind, placebo-controlled study of 434 children (2 to 18 years old) who had acute
      exacerbations of moderate or severe asthma treated in the emergency department.
      All the children received a nebulized solution of albuterol (2.5 or 5 mg per
      dose, depending on body weight) every 20 minutes for three doses and then as
      needed. A corticosteroid (2 mg of prednisone or prednisolone per kilogram of body
      weight) was given orally with the second dose of albuterol. Children in the
      treatment group received 500 microg (2.5 ml) of ipratropium bromide with the
      second and third doses of albuterol; children in the control group received 2.5
      ml of normal saline at these times. RESULTS: Overall, the rate of hospitalization
      was lower in the ipratropium group (59 of 215 children [27.4 percent]) than in
      the control group (80 of 219 [36.5 percent], P=0.05). For patients with moderate
      asthma (indicated by a peak expiratory flow rate of 50 to 70 percent of the
      predicted value or an asthma score of 8 to 11 on a 15-point scale),
      hospitalization rates were similar in the two groups (ipratropium: 8 of 79
      children [10.1 percent]; control: 9 of 84 [10.7 percent]). For patients with
      severe asthma (defined as a peak expiratory flow rate of <50 percent of the
      predicted value or an asthma score of 12 to 15), the addition of ipratropium
      significantly reduced the need for hospitalization (51 of 136 children [37.5
      percent], as compared with 71 of 135 [52.6 percent] in the control group;
      P=0.02). CONCLUSIONS: Among children with a severe exacerbation of asthma, the
      addition of ipratropium bromide to albuterol and corticosteroid therapy
      significantly decreases the hospitalization rate.

PMID- 9761805
TI  - Bilateral orchiectomy with or without flutamide for metastatic prostate cancer.
AB  - BACKGROUND: Combined androgen blockade for the treatment of metastatic prostate
      cancer consists of an antiandrogen drug plus castration. In a previous trial, we
      found that adding the antiandrogen flutamide to leuprolide acetate (a synthetic
      gonadotropin-releasing hormone that results in medical ablation of testicular
      function) significantly improved survival as compared with that achieved with
      placebo plus leuprolide acetate. In the current trial, we compared flutamide plus
      bilateral orchiectomy with placebo plus orchiectomy. METHODS: We randomly
      assigned patients who had never received antiandrogen therapy and who had distant
      metastases from adenocarcinoma of the prostate to treatment with bilateral
      orchiectomy and either flutamide or placebo. Patients were stratified according
      to the extent of disease and according to performance status. RESULTS: Of the
      1387 patients who were enrolled in the trial, 700 were randomly assigned to the
      flutamide group and 687 to the placebo group. Overall, the incidence of toxic
      effects was minimal; the only notable differences between the groups were the
      greater rates of diarrhea and anemia with flutamide. There was no significant
      difference between the two groups in overall survival (P=0.14). The estimated
      risk of death (hazard ratio) for flutamide as compared with placebo was 0.91 (90
      percent confidence interval, 0.81 to 1.01). Flutamide was not associated with
      enhanced benefit in patients with minimal disease. CONCLUSIONS: The addition of
      flutamide to bilateral orchiectomy does not result in a clinically meaningful
      improvement in survival among patients with metastatic prostate cancer.

PMID- 9761806
TI  - Images in clinical medicine. Curschmann's spirals.

PMID- 9761807
TI  - Parkinson's disease. First of two parts.

PMID- 9761808
TI  - Care of patients undergoing hemodialysis.

PMID- 9761809
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Normal reference laboratory values.

PMID- 9761810
TI  - What role for chiropractic in health care?

PMID- 9761812
TI  - Correction: Outcomes in Patients with Acute Non-Q-Wave Myocardial Infarction
      Randomly Assigned to an Invasive as Compared with a Conservative Management
      Strategy.

PMID- 9761811
TI  - Direct visualization of antigen-specific cytotoxic T cells--a new insight into
      immune defenses.

PMID- 9761813
TI  - Comparative studies of protein crystallization by vapour-diffusion and microbatch
      techniques.
AB  - Numerous reports have been published in the literature which describe the
      crystallization of macromolecules by a variety of crystallization methods,
      including the vapour-diffusion and microbatch techniques. This topical review
      compares the results of examples of proteins which were crystallized by both
      vapour-diffusion and microbatch methods. The inherent features of the vapour
      diffusion and microbatch methods are discussed and some specific conditions where
      one method appears more favourable than the other are reported. Guidelines for
      the conversion of crystallization conditions from vapour diffusion to microbatch
      (and vice versa) are also presented.

PMID- 9761814
TI  - Water molecules hydrogen bonding to aromatic acceptors of amino acids: the
      structure of Tyr-Tyr-Phe dihydrate and a crystallographic database study on
      peptides.
AB  - The crystal structure of Tyr-Tyr-Phe dihydrate contains a hydrogen bond formed
      between a water molecule and the Phe side chain. The geometry is centered with a
      distance of 3.26 A between the water O atom and the aromatic centroid. In a
      database study on hydrated peptides, four related examples are found which
      exhibit a wide variability of hydrogen-bond geometries. The intermolecular
      surroundings of the water molecules are inspected, showing that they are
      typically involved in complex networks of conventional and non-conventional
      hydrogen bonds. Possible relevance for protein hydration is given.

PMID- 9761815
TI  - Structure and proposed amino-acid sequence of a pepsin from atlantic cod (Gadus
      morhua).
AB  - The crystal structure of a pepsin from the gastric mucosa of Atlantic cod has
      been determined to 2.16 A resolution. Data were collected on orthorhombic
      crystals with cell dimensions a = 35.98, b = 75.40 and c = 108.10 A, on a FAST
      area-detector system. The phase problem was solved by the molecular-replacement
      method using porcine pepsin (PDB entry 5PEP) as a search model. The structure has
      been refined to a crystallographic R factor of 20.8% using all reflections
      between 8.0 and 2.16 A, without prior knowledge of the primary sequence. The
      resulting crystal structure is very similar to the porcine enzyme, consisting of
      two domains with predominantly beta-sheet structure in the same sequential
      positions as the enzyme from pig. In the course of the model building, 122
      residues were substituted and two residues deleted from the starting model to
      give a polypeptide chain of 324 amino acids and a sequence identity of 57.7% with
      the pig pepsin. No carbohydrate residues were located. Sequence alignment with
      available aspartic proteinases, indicates that the fish enzyme seems to be more
      related to mammalian gastric pepsins than to the mammalian gastricsins and
      chymosins, lysosomal cathepsin D's and a pepsin from tuna fish. The amino-acid
      composition of the cod enzyme, however, is more in accordance with the cathepsin
      D's.

PMID- 9761816
TI  - X-ray structure of the ZnII beta-lactamase from Bacteroides fragilis in an
      orthorhombic crystal form.
AB  - beta-Lactamases are extracellular or periplasmic bacterial enzymes which confer
      resistance to beta-lactam antibiotics. On the basis of their catalytic
      mechanisms, they can be divided into two major groups: active-site serine enzymes
      (classes A, C and D) and the ZnII enzymes (class B). The first crystal structure
      of a class B enzyme, the metallo-beta-lactamase from Bacillus cereus, has been
      solved at 2.5 A resolution [Carfi, Pares, Duee, Galleni, Duez, Frere & Dideberg
      (1995). EMBO J. 14, 4914-4921]. Recently, the crystal structure of the metallo
      beta-lactamase from Bacteroides fragilis has been determined in a tetragonal
      space group [Concha, Rasmussen, Bush & Herzberg (1996). Structure, 4, 823-836].
      The structure of the metallo-beta-lactamase from B. fragilis in an orthorhombic
      crystal form at 2.0 A resolution is reported here. The final crystallographic R
      is 0.196 for all the 32501 observed reflections in the range 10-2.0 A. The
      refined model includes 458 residues, 437 water molecules, four zinc and two
      sodium ions. These structures are discussed with reference to Zn binding and
      activity. A catalytic mechanism is proposed which is coherent with metallo-beta
      lactamases being active with either one Zn ion (as in Aeromonas hydrophila) or
      two Zn ions (as in B. fragilis) bound to the protein.

PMID- 9761817
TI  - Accelerated X-ray structure elucidation of a 36 kDa muramidase/transglycosylase
      using wARP.
AB  - The X-ray structure of the 36 kDa soluble lytic transglycosylase from Escherichia
      coli has been determined starting with the multiple isomorphous replacement
      method with inclusion of anomalous scattering at 2.7 A resolution. Subsequently,
      before any model building was carried out, phases were extended to 1.7 A
      resolution with the weighted automated refinement procedure wARP, which gave a
      dramatic improvement in the phases. The electron-density maps from wARP were of
      outstanding quality for both the main chain and the side chains of the protein,
      which allowed the time spent on the tracing, interpretation and building of the X
      ray structure to be substantially shortened. The structure of the soluble lytic
      transglycosylase was refined at 1.7 A resolution with X-PLOR to a final
      crystallographic R factor of 18.9%. Analysis of the wARP procedure revealed that
      the use of the maximum-likelihood refinement in wARP gave much better phases than
      least-squares refinement, provided that the ratio of reflections to protein atom
      parameters was approximately 1.8 or higher. Furthermore, setting aside 5% of the
      data for an Rfree test set had a negative effect on the phase improvement. The
      mean WwARP, a weight determined at the end of the wARP procedure and based on the
      variance of structure factors from six individually refined wARP models, proved
      to be a better indicator than the Rfree factor to judge different phase
      improvement protocols. The elongated Slt35 structure has three domains named the
      alpha, beta and core domains. The alpha domain contains mainly alpha-helices,
      while the beta domain consists of a five-stranded antiparallel beta-sheet flanked
      by a short alpha-helix. Sandwiched between the alpha and beta domains is the core
      domain, which bears some resemblance to the fold of the catalytic domain of the
      previously elucidated 70 kDa soluble lytic transglycosylase from E. coli. The
      putative active site is at the bottom of a large deep groove in the core domain.

PMID- 9761818
TI  - Melting points of lysozyme and ribonuclease A crystals correlated with protein
      unfolding: a Raman spectroscopic study.
AB  - The effects of a temperature increase on monoclinic and tetragonal lysozyme
      single crystals were investigated by polarizing microscopy, X-ray diffraction and
      laser Raman spectroscopy. To prevent dissolution, the mother liquor was removed,
      and the crystals were covered by the oil poly-(chlorotrifluoroethylene). Upon
      heating, their macroscopic shape was stable beyond 453 K but a change (or loss)
      of birefringence was observed around 352 and 367 K for the tetragonal and
      monoclinic crystal forms, respectively, which is associated with tighter packing
      and higher crystal forces in monoclinic lysozyme. Raman spectral changes in the
      amide I and amide III regions indicated denaturation of the protein within the
      crystalline environment at temperature where birefringence changes, and
      differences in the S-S band suggest that in monoclinic lysozyme, denaturation is
      accompanied with disruption of some S-S bonds. Comparison with thermal
      denaturation and gel formation (beta-aggregation) of lysozyme in solution
      indicates that intermolecular interactions are mainly involved in the
      stabilization of the denatured lysozyme crystals. The behavior of ribonuclease A
      is very different. This protein unfolds and refolds reversibly in solution and
      its crystals melt at the unfolding temperature at 333 K, i.e. loss of structure
      induces breakdown of crystal lattice and macroscopic shape. Although the crystal
      lattice of proteins is stabilized by only few intermolecular contacts, its
      breakdown with increasing temperature is primarily a result of thermal unfolding
      of the polypeptide chains.

PMID- 9761819
TI  - A comparison of two algorithms for electron-density map improvement by
      introduction of atomicity: skeletonization, and map sorting followed by
      refinement.
AB  - A comparison has been made of two methods for electron-density map improvement by
      the introduction of atomicity, namely the iterative skeletonization procedure of
      the CCP4 program DM [Cowtan & Main (1993). Acta Cryst. D49, 148-157] and the
      pseudo-atom introduction followed by the refinement protocol in the program suite
      DEMON/ANGEL [Vellieux, Hunt, Roy & Read (1995). J. Appl. Cryst. 28, 347-351].
      Tests carried out using the 3.0 A resolution electron density resulting from
      iterative 12-fold non-crystallographic symmetry averaging and solvent flattening
      for the Pseudomonas aeruginosa ornithine transcarbamoylase [Villeret, Tricot,
      Stalon & Dideberg (1995). Proc. Natl Acad. Sci. USA, 92, 10762-10766] indicate
      that pseudo-atom introduction followed by refinement performs much better than
      iterative skeletonization: with the former method, a phase improvement of 15.3
      degrees is obtained with respect to the initial density modification phases. With
      iterative skeletonization a phase degradation of 0.4 degrees is obtained.
      Consequently, the electron-density maps obtained using pseudo-atom phases or
      pseudo-atom phases combined with density-modification phases are much easier to
      interpret. These tests also show that for ornithine transcarbamoylase, where 12
      fold non-crystallographic symmetry is present in the P1 crystals, G-function
      coupling leads to the simultaneous decrease of the conventional R factor and of
      the free R factor, a phenomenon which is not observed when non-crystallographic
      symmetry is absent from the crystal. The method is far less effective in such a
      case, and the results obtained suggest that the map sorting followed by
      refinement stage should be by-passed to obtain interpretable electron-density
      distributions.

PMID- 9761820
TI  - Crystallization and structure solution of p53 (residues 326-356) by molecular
      replacement using an NMR model as template.
AB  - The molecular replacement method is a powerful technique for crystal structure
      solution but the use of NMR structures as templates often causes problems. In
      this work the NMR structure of the p53 tetramerization domain has been used to
      solve the crystal structure by molecular replacement. Since the rotation- and
      translation-functions were not sufficiently clear, additional information about
      the symmetry of the crystal and the protein complex was used to identify correct
      solutions. The three-dimensional structure of residues 326-356 was subsequently
      refined to a final R factor of 19.1% at 1.5 A resolution.

PMID- 9761821
TI  - Crystallization and preliminary structural studies of Scilla campanulata lectin
      complexed with alpha1-6 mannobiose.
AB  - Recent work has shown that Scilla campanulata agglutinin from bluebell bulbs has
      a strong affinity for alpha(1,3)- and alpha(1,6)-linked mannosyl residues and
      possesses moderate antiretroviral activity. This lectin has been crystallized by
      the hanging-drop method of vapour diffusion complexed with the disaccharide
      mannose-alpha1,6-D-mannose. The crystals are in the space group P21212 with unit
      cell dimensions a = 70.63, b = 92.79 and c = 47.25 A, and with a dimer in the
      asymmetric unit. The crystals diffract X-rays to beyond 1.5 A resolution at 277 K
      and are stable in an X-ray beam. Data to 1.6 A resolution have been collected
      using a MAR image-plate system at a synchrotron source and the structure of the
      complex has been solved by the molecular replacement method.

PMID- 9761823
TI  - Crystallization and preliminary X-ray analysis of the 12S form of
      phosphofructokinase from Saccharomyces cerevisiae.
AB  - The tetrameric 12S form of yeast phosphofructokinase, obtained by limited
      proteolytic cleavage of the native enzyme, was crystallized under a variety of
      conditions. The crystals have been characterized in the X-ray beam and are
      suitable for crystallographic studies.

PMID- 9761822
TI  - Expression, purification, crystallization and crystallographic characterization
      of dimeric and monomeric human neutrophil gelatinase associated lipocalin (NGAL).
AB  - Crystals of the monomeric and dimeric forms of human neutrophil gelatinase
      associated lipocalin have been grown in hanging-drop vapor-diffusion trials using
      PEG as a precipitating agent with recombinant protein expressed in a baculovirus
      based system. Crystals of monomeric NGAL belong to the cubic space group P432
      with lattice constants a = b = c = 126.6 A; crystals of dimeric NGAL belong to
      the tetragonal space group P41212 (or its enantiomorph P43212) with lattice
      constants a = b = 54.14 and c = 121.56 A. Isomorphous crystals of the NGAL dimer
      can be grown in the presence of ligand: the tripeptide N-formyl-Met-Leu-Phe.

PMID- 9761824
TI  - Crystallization and preliminary X-ray analysis of the Tet-repressor/operator
      complex.
AB  - Three crystal forms of the repressor protein TetR class D in complex with the
      palindromic 17 bp operator sequence containing T overhangs on both sides were
      obtained by hanging-drop vapor-diffusion methods using PEG 4000 and PEG
      monomethylether 5000 as precipitants. Although the crystallization conditions
      were very similar, up to three different crystal forms were observed in the same
      drop. The space groups are monoclinic C2, P21 and hexagonal P6122. The asymmetric
      units of the latter two crystal forms contain one repressor-operator complex. The
      crystal structures of these forms were solved by molecular replacement using the
      Tet-repressor molecule of the complex with tetracycline as a search model.

PMID- 9761825
TI  - Crystallization and preliminary crystallographic study of a component of the
      Escherichia coli tol system: TolB.
AB  - TolB from Escherichia coli is part of the Tol system used by the group A colicins
      to penetrate and kill cells. A TolB derivative tagged with six histidines was
      overexpressed, purified by chelation on a nickel affinity column and crystallized
      using the SAmBA software to define the optimal crystallization protocol. The
      crystals belong to the monoclinic system, space group P21 with unit-cell
      parameters a = 64.48, b = 41.06, c = 78.41 A, beta = 110.78 degrees. Frozen
      crystals diffract to 1.9 A resolution. Screening for heavy-atom derivatives both
      on the native TolB and various cysteine-substituted mutants is in progress. In
      addition, a selenomethionine-substituted protein is being produced in order to
      use the MAD method for structure determination.

PMID- 9761826
TI  - Crystallization and preliminary X-ray analysis of tyrosine aminotransferase from
      Trypanosoma cruzi epimastigotes.
AB  - Tyrosine aminotransferase from Trypanosoma cruzi has been crystallized from PEG
      4000 at pH 6.8. The crystals belong to the monoclinic space group P21 and have
      lattice constants of a = 59.1, b = 103.0, c = 77.8 A, beta = 113.1 degrees for a
      data set measured at 138 K. The presence of a non-crystallographic twofold axis
      together with a Matthews parameter Vm of 2.5 A3 Da-1 indicates that the
      asymmetric unit contains one dimeric molecule. The crystals diffract to at least
      2.7 A and are stable in the X-ray beam in a shock-frozen state. Native data sets
      have been collected at temperatures of 285 and 138 K using a Siemens X1000
      detector on a rotating-anode generator.

PMID- 9761827
TI  - Crystallization and preliminary X-ray analysis of human platelet profilin
      complexed with an oligo proline peptide.
AB  - Profilin is an actin-monomer binding protein that regulates the distribution and
      dynamics of the actin cytoskeleton. Profilin binds poly-L-proline and proline
      rich peptides in vitro and co-localizes with proline-rich proteins in focal
      adhesions and at the site of actin tail assembly on the surface of intracellular
      parasites such as Listeria monocytogenes. The crystallization of the complex
      between human platelet profilin (HPP) and an L-proline decamer [(Pro)10] is
      reported here. Diffraction from these crystals is consistent with the space group
      P21212 with unit-cell constants a = 68.25, b = 97.64, c = 39.10 A. The crystals
      contain two HPP molecules per asymmetric unit and diffract to 2.2 A.

PMID- 9761828
TI  - Crystallization and preliminary X-ray studies of sialidase L from the leech
      Macrobdella decora.
AB  - Functional monomeric 83 kDa sialidase L, a NeuAcalpha2-->3Gal-specific sialidase
      from Macrobdella leech, was expressed in Escherichia coli and readily
      crystallized by a macroseeding technique. The crystal belongs to space group P1
      with unit-cell parameters a = 46.4, b = 69.3, c = 72.5 A, alpha = 113.5, beta =
      95.4 and gamma = 107.3 degrees. There is one molecule per unit cell, giving a Vm
      = 2.4 A3 Da-1 and a solvent content of 40%. Native and mercury-derivative data
      sets were collected to 2.0 A resolution. Threading and molecular-replacement
      calculations confirmed the existence of a bacterial sialidase-like domain.

PMID- 9761829
TI  - Crystallization of the catalytic domain of Clostridium cellulolyticum CeLF
      cellulase in the presence of a newly synthesized cellulase inhibitor.
AB  - The catalytic domain of the CeIF processive endocellulase, a family 48 glycosyl
      hydrolase from Clostridium cellulolyticum has been crystallized in the presence
      of a newly synthesized inhibitor (methyl 4-S-beta-cellobiosyl-4-thio-beta
      cellobioside), by vapour diffusion, using PEG as a precipitant. The protein
      crystallizes in the orthorhombic P212121 space group and diffracts to a
      resolution of 2.0 A. The unit-cell parameters are a = 61.4, b = 84.5, c = 121.9
      A.

PMID- 9761830
TI  - Crystallization and preliminary crystallographic investigation of porcine
      quinolinate phosphoribosyltransferase.
AB  - Quinolinate phosphoribosyltransferase (QPRT), purified from hog liver, has been
      crystallized using PEG 8000 as the precipitant. The crystals form long hexagonal
      rods in the space group P6322 with cell dimensions a = b = 121.7, c = 94.5 A.
      Based on the unit-cell dimensions and the calculated molecular mass of 33 500 Da,
      the Matthews coefficient suggests one molecule per asymmetric unit (Vm = 3.45 A3
      Da-1; 64% solvent). Three native data sets were collected to a resolution of 2.5
      A and merged to provide a set that is 94.7% complete, with an Rsym value of 9.6%.

PMID- 9761831
TI  - Crystallization and preliminary X-ray crystallographic analysis of the helicase
      domain of hepatitis C virus NS3 protein.
AB  - The NS3 protein of hepatitis C virus (HCV) is thought to be essential for viral
      replication. The N-terminal domain of the protein contains protease activity and
      the C-terminal domain contains nucleotide triphosphatase and RNA helicase
      activity. The RNA helicase domain of HCV NS3 protein was purified by using
      affinity-column chromatographic methods, and crystallized by using the microbatch
      crystallization method under oil at 277 K. The crystals belong to primitive
      trigonal space group P3121 or P3221 with cell dimensions of a = b = 93.3, c =
      104.6 A. The asymmetric unit contains one molecule of the helicase domain, with
      the crystal volume per protein mass (Vm) of 2.50 A3 Da-1 and solvent content of
      about 50.8% by volume. A native data set to 2.3 A resolution was obtained from a
      frozen crystal indicating that the crystals are quite suitable for structure
      determination by multiple isomorphous replacement.

PMID- 9761832
TI  - Crystallization of Arthrobacter sp. strain 1C N-(1-D-carboxyethyl)-L-norvaline
      dehydrogenase and its complex with NAD+
AB  - The novel NAD+-linked opine dehydrogenase from a soil isolate Arthrobacter sp.
      strain 1C belongs to an enzyme superfamily whose members exhibit quite diverse
      substrate specificites. Crystals of this opine dehydrogenase, obtained in the
      presence or absence of co-factor and substrates, have been shown to diffract to
      beyond 1.8 A resolution. X-ray precession photographs have established that the
      crystals belong to space group P21212, with cell parameters a = 104.9, b = 80.0,
      c = 45.5 A and a single subunit in the asymmetric unit. The elucidation of the
      three-dimensional structure of this enzyme will provide a structural framework
      for this novel class of dehydrogenases to enable a comparison to be made with
      other enzyme families and also as the basis for mutagenesis experiments directed
      towards the production of natural and synthetic opine-type compounds containing
      two chiral centres.

PMID- 9761833
TI  - Crystallization and preliminary X-ray diffraction studies of bleomycin-binding
      protein from bleomycin-producing Streptomyces verticillus.
AB  - A bleomycin-binding protein (BLMA) produced by bleomycin-producing Streptomyces
      verticullus was crystallized in a form suitable for X-ray diffraction analysis
      using the vapor-diffusion method. Crystals were grown at pH 5.7, in 0.2 M NH4
      actate and 0.1 M Na acetate, using 30% PEG 4000 as a precipitant. They belong to
      the orthorhombic system, with space group P21212, cell dimensions a = 54. 90, b =
      67.94, c = 35.60 A, and one BLMA molecule in the asymmetric unit. The crystals
      diffract X-rays well and the diffraction intensity data was collected up to 1.5 A
      resolution with a merging R value of 0.054 at beamline 6B of the Photon Factory.
      The diffraction data set is 94% complete.

PMID- 9761834
TI  - Crystallization and preliminary X-ray diffraction studies of a family 26 endo
      beta-1,4 mannanase (ManA) from Pseudomonas fluorescens subspecies cellulosa.
AB  - Crystals of an endo-beta-1,4-mannanase (1,4-beta-D-mannohydrolase, E. C.
      3.2.1.78) from Pseudomonas fluorescens sub species cellulosa have been grown by
      the hanging-drop technique at 291 K over a period of one to two weeks to maximal
      dimensions of 0.17 x 0.17 x 0.25 mm. These crystals belong to the space group R32
      (or R3) with cell dimensions of a = b = 155.4 and c = 250.8 A (hexagonal setting)
      and contain three (six) molecules in the asymmetric unit. The crystals diffract
      to at least 3.2 A using a laboratory source and are suitable for structure
      determination.

PMID- 9761835
TI  - Crystallization and preliminary X-ray analysis of the periplasmic receptor (PotF)
      of the putrescine transport system in Escherichia coli.
AB  - The primary receptor (PotF) of the putrescine transport system in E. coli has
      been crystallized by the hanging-drop vapor-diffusion technique. The crystals
      belong to the space group P21212 with unit-cell dimensions a = 269.4, b = 82.33
      and c = 93.74 A. The crystals diffract beyond 2.2 A with a rotating-anode X-ray
      source. A complete data set from the native crystals has been collected and
      processed at 2.3 A resolution. Two heavy-atom derivatives have been prepared from
      the same Pt compound at 293 and 277 K. The difference Patterson maps revealed
      completely different major heavy-atom sites between these two derivatives.

PMID- 9761836
TI  - The FNR-like domain of the Escherichia coli sulfite reductase flavoprotein
      component: crystallization and preliminary X-ray analysis.
AB  - The FNR-like domain of the Escherichia coli sulfite reductase flavoprotein
      subunit was crystallized using the hanging-drop technique, with PEG 4000 as
      precipitant. The crystals belong to space group P3112 or enantiomorph, with unit
      cell parameters a = b = 171.0, c = 152.1 A. A solvent content of 75% was
      determined by a calibrated tetrachloromethane/toluene gradient which corresponds
      to three monomers per asymmetric unit. A 3 A resolution native data set was
      collected at beamline W32 of LURE, Orsay, France.

PMID- 9761837
TI  - Crystallization and preliminary crystallographic analyses of pokeweed antiviral
      protein from seeds.
AB  - Pokeweed antiviral protein from seeds (PAP-S) is a ribosome inactivating protein
      which has lowest toxicity and highest inhibition activity as opposed to other
      pokeweed antiviral proteins and its three potential glycosylation sites (10, 44,
      255) were shown to bind to N-acetylglucosamine. Good quality crystals of PAP-S
      were grown at high protein concentration (100 mg ml-1) and high temperature (306
      K). The crystals have space group I222 and cell parameters a = 78.7, b = 85.2 and
      c = 93.0 A. An X-ray diffraction data set with resolution up to 1.8 A was
      collected. This high-resolution data will help to locate the sugars bound to the
      protein and provide accurate structural data for understanding structure-function
      relationships of PAP-S.

PMID- 9761838
TI  - Crystallization of a complex between a novel C-terminal transmitter, HPt domain,
      of the anaerobic sensor kinase ArcB and the chemotaxis response regulator CheY.
AB  - The histidine-containing phosphotransfer (HPt) domain at the C-terminus of the
      anaerobic sensor kinase ArcB has been cocrystallized with the chemotaxis response
      regulator CheY by a hanging-drop vapor-diffusion method. Crystals belong to space
      group P212121 with unit-cell dimensions a = 55.32, b = 76.29 and c = 83.89 A,
      with one molecule in the crystallographic asymmetric unit. The crystals diffract
      to 2.7 A resolution. This is the first crystallization of a protein-protein
      complex formed by a transmitter domain of sensor kinase and a receiver domain of
      response regulator in the two-component signal-transduction system.

PMID- 9761839
TI  - Expression, purification and crystallization of the catalytic subunit of protein
      kinase CK2 from Zea mays.
AB  - The catalytic (alpha) subunit of protein kinase CK2 (CK2alpha) was originally
      cloned and overexpressed in the Escherichia coli strain pT7-7/BL21(DE3). The
      protein has been purified to homogeneity and crystallized. The crystals belong to
      the monoclinic space group C2, they have unit-cell parameters a = 142.6, b =
      61.3, c = 45.6 A, beta = 103.3 degrees and diffract X-rays to at least 2.0 A
      resolution. The calculated crystal packing parameter is Vm = 2.47 A3 Da-1
      suggesting that one CK2alpha molecule is contained in the asymmetric unit and
      that the solvent content of the unit cell is 50%.

PMID- 9761840
TI  - Crystals of bovine heart ubiquinol-cytochrome c reductase diffracting X-rays up
      to 2.8 A resolution at 276 K.
AB  - Bovine heart ubiquinol-cytochrome c reductase stabilized with sucrose monocaplate
      was crystallized with polyethylene glycol as the precipitant at 277 K. X-rays
      diffracted by the crystal were detected up to 2.8 A resolution at 266 K, without
      using a synchrotron source. The space group and cell dimensions are P61 or P65
      and a = b = 128.5 and c = 715.7 A, respectively.

PMID- 9761841
TI  - Preliminary X-ray crystallographic studies of a newly defined human theta-class
      glutathione transferase.
AB  - Human theta-class glutathione S-transferases (GST's) appear to play a critical
      role in the metabolism of a variety of environmental pollutants but in some cases
      the products of the reaction are carcinogenic. Crystals of a human theta-class
      GST, namely hGSTT2-2, have been grown from polyethylene glycol by the hanging
      drop vapour-diffusion method. The crystals belong to the trigonal space group
      P3121 with cell dimensions of a = b = 94.0 and c = 120.5 A. They contain two
      monomers in the asymmetric unit and diffract to 3.0 A resolution.

PMID- 9761842
TI  - Romit profile analysis for molecular replacements.
AB  - A new procedure for evaluation of molecular replacement has been examined by
      using an R factor calculated from the probe structure with some omitted parts
      (Romit). It has been demonstrated that changes in Romit from the conventional R
      factor for the whole structure are sensitive to the local fitness in the omitted
      region even for large molecules such as proteins. Their profile, plotted against
      residues, is effective for distinguishing the most probable one from several
      solutions. In addition, this profile analysis exhibits useful information for
      model building.

PMID- 9761843
TI  - Structure of sulfur-substituted rhodanese at 1.36 A resolution.
AB  - 1.36 A resolution X-ray diffraction data have been recorded at 100 K for bovine
      liver sulfur-substituted rhodanese, using synchrotron radiation. The crystal
      structure has been refined anisotropically to a final R factor of 0.159 (Rfree =
      0.229) for 53034 unique reflections. The model contains 2327 protein atoms and
      407 solvent molecules, with a good geometry. The high resolution allows full
      details for helices, beta-sheets, tight turns and of all inter- and
      intramolecular interactions stabilizing the enzyme molecule to be given. The
      situation at the active site is described, particularly in regard to the network
      of hydrogen bonds made by Sgamma and Sdelta of the sulfur-substituted catalytic
      Cys247 and surrounding groups and solvent molecules. The replacement of the
      precipitant ammonium sulfate with cryoprotectants in the crystal-suspending
      medium led to the removal of the sulfate ion from the enzyme active site. Only
      limited changes of the enzyme structure have been found as a result of the
      drastic change in the crystal medium.

PMID- 9761844
TI  - Miscellaneous algorithms for density modification.
AB  - Various algorithms are described, developed for the dm density modification
      package, which have not been described elsewhere. Methods are described for the
      following problems: determination of the absolute scale and overall temperature
      factor of a data set, by a method which is less dependent on data resolution than
      Wilson statistics; an efficient interpolation algorithm for averaging and its
      application to refinement of averaging operators; a method for the automatic
      determination of averaging masks.

PMID- 9761846
TI  - Structure of d(CACGCG).d(CGCGTG) in crystals grown in the presence of ruthenium
      III hexammine chloride.
AB  - Hexammine ions are strong inducers of the transition from the B-form to the left
      handed Z-form in DNA. Here the structure of d(CACGCG). d(CGCGTG) obtained from
      crystals grown from a drop containing [Ru(NH3)6]Cl3 is reported. The structure is
      clearly characterized as Z-DNA. When compared with the structure of
      d(CACGCG).d(CGCGTG)/MgCl2 and that of d(CGCGCG)2, subtle differences are seen,
      most noticeably in the water structure. Since stable well diffracting crystals
      grow easily in the presence of [Ru(NH3)6]Cl3 and since this ion is not visible in
      the electron density it is concluded that the ion plays a non-specific role in
      stabilizing Z-DNA.

PMID- 9761847
TI  - Structure of a basic phospholipase A2 from Agkistrodon halys Pallas at 2.13 A
      resolution.
AB  - The basic phospholipase A2 isolated from the venom of Agkistrodon halys Pallas
      (Agkistrodon blomhoffii Brevicaudus) is a hemolytic toxin and one of the few
      PLA2's capable of hydrolyzing the phospholipids of E. coli membranes in the
      presence of a bactericidal/permeability-increasing protein (BPI) of neutrophils.
      The crystal structure has been determined and refined at 2.13 A to an R factor of
      16.5% (F > 3sigma) with excellent stereochemistry. A superposition of the two
      molecules in the asymmetric unit gives an r. m.s. deviation of 0.326 A for all
      Calpha atoms. The refined structure allowed a detailed comparison with other PLA2
      species of known structures. The overall architecture is similar to those of
      other PLA2's with a few significant differences. One of which is in the region
      connecting the N-terminal helix and the Ca2+-binding loop. Unexpectedly, the
      conformation of the peptide plane Cys29-Gly30 in the Ca2+-binding loop is very
      different to that of other PLA2's. The amide NH of Gly30 does not point toward
      the proposed site for stabilization of the tetrahedral intermediate oxyanion of
      the substrate analogue. The structure includes four residues which occur less
      frequently in other PLA2's. His1, Arg6 and Trp70 located at the interfacial
      recognition site may play an important role in the interaction with aggregated
      substrates, while Trp77 contributes to the hydrophobic interactions between the
      beta-wing and the main body of the molecule. This structure analysis reveals that
      two clusters of basic residues are located at or near the interfacial recognition
      site, forming an asymmetric positively charge distribution. In contrast to the
      acidic isoform, the present enzyme is a dimer in the crystalline state. The
      special phospholipid hydrolysis behaviors are discussed in the light of the
      structure determined.

PMID- 9761848
TI  - Refinement of triclinic hen egg-white lysozyme at atomic resolution.
AB  - X-ray diffraction data have been collected at both low (120 K) and room
      temperature from triclinic crystals of hen egg-white lysozyme to 0.925 and 0.950
      A resolution, respectively, using synchrotron radiation. Data from one crystal
      were sufficient for the low-temperature study, whereas three crystals were
      required at room temperature. Refinement was carried out using the programs
      PROLSQ, ARP and SHELXL to give final conventional R factors of 8.98 and 10.48%
      for data with F > 4sigma(F) for the low- and room-temperature structures,
      respectively. The estimated r.m.s. coordinate error is 0.032 A for protein atoms,
      0.050 A for all atoms in the low-temperature study, and 0.038 A for protein atoms
      and 0.049 A for all atoms in the room-temperature case, as estimated from
      inversion of the blocked least-squares matrix. The low-temperature study revealed
      that the side chains of 24 amino acids had multiple conformations. A total of 250
      waters, six nitrate ions and three acetate ions, two of which were modelled with
      alternate orientations were located in the electron-density maps. Three sections
      of the main chain were modelled in alternate conformations. The room-temperature
      study produced a model with multiple conformations for eight side chains and a
      total of 139 water molecules, six nitrate but no acetate ions. The occupancies of
      the water molecules were refined in both structures and this step was shown to be
      meaningful when assessed by use of the free R factor. A detailed description and
      comparison of the structures is made with reference to the previously reported
      structure refined at 2.0 A resolution.

PMID- 9761849
TI  - Rfree and the rfree ratio. I. Derivation of expected values of cross-validation
      residuals used in macromolecular least-squares refinement.
AB  - The last five years have seen a large increase in the use of cross validation in
      the refinement of macromolecular structures using X-ray data. In this technique a
      test set of reflections is set aside from the working set and the progress of the
      refinement is monitored by the calculation of a free R factor which is based only
      on the excluded reflections. This paper gives estimates for the ratio of the free
      R factor to the R factor calculated from the working set for both unrestrained
      and restrained refinement. It is assumed that both the X-ray and restraint
      observations have been weighted correctly and that there is no correlation of
      errors between the test and working sets. It is also shown that the least-squares
      weights that minimize the variances of the refined parameters, also approximately
      minimize the free R factor. The estimated free R-factor ratios are compared with
      those reported for structures in the Protein Data Bank.

PMID- 9761850
TI  - Structure of holo-glyceraldehyde-3-phosphate dehydrogenase from Palinurus
      versicolor refined at 2 A resolution.
AB  - The crystal structure of holo-glyceraldehyde-3-phosphate dehydrogenase from
      Palinurus versicolor, South China sea lobster, was determined and refined at 2 A
      resolution to an R factor of 17.1% and reasonable stereochemistry. The structure
      refinement has not altered the overall structure of GAPDH from this lobster
      species. However, some local changes in conformation and the inclusion of ordered
      solvent model have resulted in a substantial improvement in the accuracy of the
      structure. Structure analysis reveals that the two subunits including NAD+ in the
      asymmetric unit are remarkably similar. The thermal differences between the two
      subunits found in some regions of the NAD+-binding domain may originate from
      different crystallographic environments rather than from an inherent molecular
      asymmetry. In this structure, the side chain of Arg194 does not point toward the
      active site but forms an ion pair with Asp293 from a neighboring subunit.
      Structural comparisons with other GAPDH's of known structure reveal that obvious
      contrast exists between mesophilic and thermophilic GAPDH mainly in the catalytic
      domain with significant conformational differences in the S-loop, beta7-strand
      and loop 120-125; the P-axis interface is more conserved than the R- and Q-axis
      interfaces and the catalytic domain is more conserved than the NAD+-binding
      domain. Some possible factors affecting the thermostability of this enzyme are
      tentatively analyzed by comparison with the highly refined structures of
      thermophilic enzymes.

PMID- 9761851
TI  - 1.76 A structure of a pyrimidine start alternating A-RNA hexamer r(CGUAC)dG.
AB  - The crystal structure of the alternating RNA r(CGUAC)dG with a 3'-terminal deoxy
      G residue has been determined at 1.76 A resolution. The crystal belongs to the
      orthorhombic space group C2221, unit-cell dimensions a = 29.53, b = 44.61 and c =
      94.18 A, with two independent duplexes (I and II) per asymmetric unit. The
      structure was solved by the molecular-replacement method. The final R factor was
      18.8% using 4757 reflections in the resolution range 8.0-1.76 A. The model
      contains a total of 496 atoms and 85 solvent molecules. The two duplexes form the
      repeating unit and stack in the usual head-to-tail (5',3'/5',3') fashion into a
      pseudocontinuous helical column. Almost all of the 2'-hydroxyl groups are engaged
      in the three modes of water-mediated interactions to the base N3/O2 atoms, the
      sugar O4' atoms and the backbone phosphates. Thus, the 2'-hydroxyl group of RNA
      is probably contributing to the stability of the duplexes.

PMID- 9761852
TI  - Structure of the DNA decamer d(GGCAATTGCG) contains both major- and minor-groove
      binding G.(G.C) base triplets.
AB  - The crystal structure of the decamer d(GGCAATTGCG) has been determined at 2.4 A
      resolution. The central eight bases of each DNA single-strand base pair with a
      self-complementary strand to form an octamer B-DNA duplex. These duplexes lie end
      to-end within the unit cell. The terminal 5'-G and G-3' bases of each decamer
      strand are unpaired, and interact with the neighbouring duplexes via interactions
      within both the major and minor groove. This results in base triplets of the type
      G-(G.C) and G*(G.C), with the third guanine base binding to a Watson-Crick G.C
      base pair from the major groove and the minor groove, respectively. The triplet
      interaction of the type G-(G.C) involves Hoogsteen hydrogen-bonding interactions
      between the two guanine bases. The minor- and major-groove base triplet
      interactions which exist within this structure act to stabilize the d(GCAATTGC)2
      B-DNA octamer duplex.

PMID- 9761853
TI  - Structural evidence for the aromatic-(i+1) amine hydrogen bond in peptides: L-tyr
      L-tyr-L-Leu monohydrate.
AB  - In crystalline Tyr-Tyr-Leu monohydrate, an aromatic-(i+1) amine hydrogen bond is
      observed, that is a weak hydrogen-bond-type interaction between an aromatic side
      chain and N-H of the next peptide group in the main chain. Unlike the better
      investigated aromatic-(i+2) amine hydrogen bonds, which can adopt almost ideal
      geometries, the geometry of the discussed interaction is very distorted because
      of steric constraints. Presumably, this kind of weak hydrogen bond is only formed
      as a last resort if N-H finds it impossible to engage in the much stronger
      conventional hydrogen bonding with O-atom acceptors.

PMID- 9761854
TI  - Structure of the Kunitz-type soybean trypsin inhibitor (STI): implication for the
      interactions between members of the STI family and tissue-plasminogen activator.
AB  - The Kunitz-type soybean trypsin inhibitor (STI) has played a key role in the
      early study of proteinases, having been used as the main substrate in the
      biochemical and kinetic work that led to the definition of the standard mechanism
      of action of proteinase inhibitors. A partial structure of STI complexed with
      porcine trypsin has previously been reported, in which the first 93 residues of
      the inhibitor, including the region of contact with trypsin, were relatively well
      defined, whereas for the remaining part of the peptide chain only some Calpha
      atoms were located. The structure of the inhibitor in its free form has now been
      determined by molecular replacement to 2.5 A, using the coordinates of the
      homologous Erythrina trypsin inhibitor as a search model. When the refined atomic
      coordinates of STI are compared with the partial model previously available, the
      conformation of the reactive-site loop and its position with respect to the main
      body of the molecule does not change when the inhibitor interacts with trypsin.
      There are instead, despite the high similarity in the overall tertiary structure,
      significant differences between STI and Erythrina trypsin inhibitor (ETI) in the
      region which is in contact with the enzyme in the STI:trypsin crystal structure.
      Some of these differences can explain the unique specificity of ETI and its
      ability to inhibit the fibrinolytic enzyme tissue-type plasminogen activator.

PMID- 9761855
TI  - Atomic resolution structure of human HBP/CAP37/azurocidin.
AB  - Crystals of human heparin binding protein (HBP) diffract to 1.1 A when flash
      frozen at 120 K. The atomic resolution structure has been refined anisotropically
      using SHELXL96. The final model of HBP consists of 221 amino-acid residues of 225
      possible, three glycosylation units, one chloride ion, 15 precipitant ethanol
      molecules and 323 water molecules. The structure is refined to a final
      crystallographic R factor of 15.9% and Rfree(5%) of 18.9% using all data. A
      putative protein kinase C activation site has been identified, involving residues
      113-120. The structure is compared to the previously determined 2.3 A resolution
      structure of HBP.

PMID- 9761856
TI  - On the choice of an optimal wavelength in macromolecular crystallography.
AB  - Potential benefits of using short X-ray wavelengths for protein crystal data
      collection arise from a reduction in absorption errors and a decrease in
      radiation damage of a sample. On the other hand, at longer wavelengths one may
      benefit from an increase in scattering efficiency of a crystal and an increase in
      intensity of an incident beam at a given synchrotron beamline. For small and
      frozen crystals the negative effects of absorption and radiation damage would be
      minimized which may shift the balance of interests towards the use of longer
      wavelengths. Experiments carried out at EMBL beamlines at DESY (Hamburg) show an
      advantage of using wavelengths longer than 1 A for data collection from crystals
      of up to 0.5 mm.

PMID- 9761857
TI  - Direct phase determination in protein electron crystallography: aquaporin channel
      forming integral membrane protein.
AB  - The location of helix sites in the projected structure of the aquaporin channel
      forming integral membrane protein from bovine red blood cells was determined by
      multisolution direct methods to a mean accuracy of +/-1.9 A, based on hk0
      electron diffraction data extending to 6 A. The structure was assumed to be
      composed of pseudo-atoms, corresponding to the helix cross sections, and after re
      scaling, normalized structure factors were used to order summation operatorn
      triples according to the A values. Initial phases were found by symbolic addition
      with algebraic unknowns. Probable solutions could be isolated by an overall
      Luzzati test for density flatness and restrictions on local density extremes. The
      best solution was identified by matching Patterson functions, generated from the
      trial map density sites, to the one calculated from observed intensities.

PMID- 9761858
TI  - Macromolecular crystal annealing: overcoming increased mosaicity associated with
      cryocrystallography.
AB  - Although cryogenic data collection has become the method of choice for
      macromolecular crystallography, the flash-cooling step can dramatically increase
      the mosaicity of some crystals. Macromolecular crystal annealing significantly
      reduces the mosaicity of flash-cooled crystals without affecting molecular
      structure. The process, which cycles a flash-cooled crystal to ambient
      temperature and back to cryogenic temperature, is simple, quick and requires no
      special equipment. The annealing process has been applied to crystals of several
      different macromolecules grown from different precipitants and using a variety of
      cryoprotectants. The protocol for macromolecular crystal annealing also has been
      applied to restore diffraction from flash-cooled crystals that were mishandled
      during transfer to or from cryogenic storage. These results will be discussed in
      relation to crystal mosaicity and effects of radiation damage in flash-cooled
      crystals.

PMID- 9761859
TI  - Structure determination of a 16.8 kDa copper protein at 2.1 A resolution using
      anomalous scattering data with direct methods.
AB  - The structure of rusticyanin, an acid-stable copper protein, has been determined
      at 2.1 A resolution by direct methods combined with the single-wavelength
      anomalous scattering (SAS) of copper (f" = 3.9 e-) and then conventionally
      refined (Rcryst = 18.7%, Rfree = 21.9%). This is the largest unknown protein
      structure (Mr approximately /= 16.8 kDa) to be determined using the SAS and
      direct-methods approach and demonstrates that by exploiting the anomalous signal
      at a single wavelength, direct methods can be used to determine phases at typical
      (approximately 2 A) macromolecular crystallographic resolutions. Extrapolating
      from the size of the anomalous signal for copper (f" approximately 4 e-), this
      result suggests that the approach could be used for proteins with molecular
      weights of up to 33 kDa per Se (f"max++ = 8 e- at the 'white line') and 80 kDa
      for a Pt derivative (f"max = 19 e- at the 'white line', L3 edge). The method
      provides a powerful alternative in solving a de novo protein structure without
      either preparing multiple crystals (i.e. isomorphous heavy-atom derivative plus
      native crystals) or collecting multi-wavelength anomalous diffraction (MAD) data.

PMID- 9761860
TI  - Crystallization and preliminary X-ray study of saporin, a ribosome-inactivating
      protein from Saponaria officinalis.
AB  - Single crystals of the protein saporin isolated from the seeds of S. officinalis
      have been grown by the vapor-diffusion method using ammonium sulfate as
      precipitant. The crystals are tetragonal, space group P4122 (P4322), with cell
      dimensions a = b = 67.53 and c = 119. 67 A, and diffract to 2.0 A resolution on a
      rotating-anode X-ray source. The asymmetric unit contains one molecule,
      corresponding to a volume of the asymmetric unit per unit mass (Vm) of 2.38 A3 Da
      1.

PMID- 9761861
TI  - Purification, crystallization and preliminary X-ray diffraction studies of
      retinal dehydrogenase type II.
AB  - One enzyme which catalyzes the last step of the formation of the hormone retinoic
      acid from vitamin A (retinol) is retinal dehydrogenase type II (Ra1DH2). Ra1DH2,
      expressed in the Escherichia coli BL21(DE3) strain, was purified and crystallized
      using ammonium sulfate as a precipitant. These crystals belong to the space group
      P212121 (a = 108, b = 150, c = 168 A, alpha = beta = gamma = 90 degrees).

PMID- 9761863
TI  - Purification, crystallization and preliminary X-ray analysis of the Escherichia
      coli phytase.
AB  - A recombinant form of Escherichia coli phytase, which hydrolyzes phytic acid into
      phosphate and myo-inositol, has been expressed, purified and crystallized.
      Crystals have been obtained by the method of bulk crystallization in 10 mM sodium
      acetate buffer (pH 4.5) without using a conventional precipitant. The enzyme
      crystallized in space group P21, with unit-cell dimensions a = 74.9, b = 72.2, c
      = 82.4 A, and beta = 92.0 degrees. Crystals diffract to at least 2.2 A at a
      rotating-anode X-ray source and a 2.3 A resolution data set has been collected,
      giving completeness of 98.0% and an Rsym of 0.072. Assuming there are two phytase
      molecules in the asymmetric unit, the solvent content is calculated to be 42.1%.
      A self-rotation function shows a clear twofold non-crystallographic symmetry
      relating two molecules of E. coli phytase in the asymmetric unit.

PMID- 9761862
TI  - Crystallization of human complement component C5.
AB  - Human complement component C5 has been crystallized using a low-salt batch
      technique. The crystals are large hexagonal bi-pyramids often larger than 1.5 mm.
      Although these crystals were grown in low salt (0.1 M NaCl), they are remarkably
      stable for at least 2 months at 281 K and they are not dissolved in aqueous
      buffers containing up to 2 M sodium chloride. The space group is P3121 or P3221,
      and the cell parameters were determined to be a = 144.9, b = 144.9, c = 243.1 A;
      alpha = 90 degrees, beta = 90, gamma = 120 degrees. At room temperature and cryo
      temperatures the crystals diffract at best to 6 A using rotating-anode X-ray
      sources. Using synchrotron radiation with cryoprotection using 40%(v/v) PEG 400
      the resolution limit can be extended to 3.3 A. In both cases the crystals show
      significant anisotropy, with relatively weaker reflections at higher resolution
      in the a*b* plane.

PMID- 9761864
TI  - Crystallization and preliminary X-ray crystallographic studies of the native and
      chemically modified anion-selective porin from Comamonas acidovorans.
AB  - Omp32, the strongly anion-selective porin from Comamonas acidovorans, has been
      crystallized. Two crystal forms were observed, both of which belong to space
      group R3, but exhibit different cell dimensions a = b = 106.7, c = 140.6 A
      (crystal form I) and a = b = 87.1, c = 135.3 A (crystal form II) with one trimer
      per asymmetric unit. The crystals diffract to 2.2 and 2.3 A resolution,
      respectively. Omp32 was chemically modified by introducing negative charges
      through succinylation. The number and positions of the individual modifications
      were determined using mass spectrometry and X-ray crystallography. Chemically
      modified porins yielded crystals of a third form, also of space group R3 but with
      cell constants of a = b = 109.3 and c = 263.2 A (crystal form III), showing a
      virtually doubled c axis. Crystals of form III diffract to 3.5 A resolution.

PMID- 9761865
TI  - Crystallization and preliminary crystallographic studies of chloroplast NADP
      dependent malate dehydrogenase from Flaveria bidentis.
AB  - Crystals of chloroplast NADP-dependent malate dehydrogenase have been grown both
      with and without the cofactor NADP present. The enzyme has a molecular weight of
      43 kDa per subunit and exists as a dimer in solution. The crystals diffract to
      2.8 A and belong to the space group P3221 with cell dimensions a = 148.1, c =
      65.5 A.

PMID- 9761866
TI  - Crystallization and preliminary X-ray analysis of IND, an enzyme with indole
      oxygenase activity from Chromobacterium violaceum.
AB  - IND, a redox flavoprotein from Chromobacterium violaceum has been crystallized in
      the presence and absence of NADH. The crystals belong to the space group P41212
      or its enantiomorph P43212 with a = 73.9 and c = 153.6 A. There is one molecule
      per asymmetric unit and the crystals diffract beyond 2.1 A resolution.

PMID- 9761867
TI  - Crystallization and preliminary X-ray diffraction analysis of aspartate
      aminotransferase from Saccharomyces cerevisiae.
AB  - Diffraction-quality crystals of S. cerevisiae cytoplasmic aspartate
      aminotransferase have been obtained by the hanging-drop vapor-diffusion method in
      the presence of pyridoxal phosphate and maleic acid, sodium acetate, ammonium
      acetate and polyethylene glycol. The crystals have the symmetry of the
      orthorhombic space groups P212121 or P21212 with unit-cell dimensions a = 130.2,
      b = 134.6 and c = 98.7 A. Square rod-shaped crystals with dimensions of
      approximately 0.2 x 0.2 x 0.5 mm diffract to spacings of 2 A. The calculated
      value of the Matthews coefficient, Vm = 2.4 A3 Da-1, is consistent with four
      subunits of aspartate aminotransferase per asymmetric unit.

PMID- 9761868
TI  - Crystallization and preliminary X-ray studies of allophycocyanin from red alga
      Porphyra yezoensis.
AB  - Allophycocyanin from red alga Porphyra yezoensis has been crystallized in three
      crystal forms. Form 1 crystals with space group P4132 or P4332 and cell
      parameters a = 286 A, alpha = 90 degrees were obtained by using isopropanol as
      precipitant. These crystals did not diffract beyond 5.8 A and could not be used
      in structure analysis. Form 2 crystals were obtained when crystallization
      conditions were slightly changed by adding 0.2 M magnesium chloride. The space
      group of form 2 was not determined because it was difficult to get large single
      crystals. Form 3 crystals were obtained by using ammonium sulfate as precipitant.
      The space group of form 3 is R32 with cell dimensions a = b = 105.3, c = 189.4 A
      and one alpha beta unit in the asymmetric unit. These crystals diffract up to
      2.06 A resolution and are suitable for structure determination by molecular
      replacement methods.

PMID- 9761869
TI  - Scilla campanulata agglutinin crystallized in complex with the trimannoside alpha
      D-man-(1-->6)-[alpha-D-man-(1-->3)]-alpha-D-Man.
AB  - The monocot mannose-specific lectin, Scilla campanulata agglutinin (SCA), from
      bluebell bulbs has a strong affinity for alpha1,3- and alpha1,6-linked mannosyl
      residues. SCA has been co-crystallized with the trisaccharide alpha-D
      mannopyranosyl-(1-->6)-alpha-D-mannopyranosyl-(1-->3)-alpha-D -mannopyranoside
      ?alpha-D-Man-(1-->6)-[alpha-D-Man-(1-->3)]-alpha-D-Man?, the core structure of
      biantennary N-linked oligosaccharides. Crystals of the complex were obtained by
      the hanging-drop vapour-diffusion technique. A complete data set to 2.5 A
      resolution has been collected at 100 K, using a MAR image-plate system at a
      synchrotron source, from crystals which belong to the space group C2 with unit
      cell dimensions a = 99.38, b = 119.86, c = 77.10 A and beta = 105.56 degrees. Use
      of a CCD detector with cryo-cooled crystals improved the resolution to 2.3 A. A
      molecular replacement solution, with the 2.5 A data set, using the native SCA as
      a search model was obtained, with six subunits per asymmetric unit.

PMID- 9761870
TI  - Preliminary X-ray crystallographic study of wild-type and mutant ribulose-1,5
      bisphosphate carboxylase/oxygenase from Chlamydomonas reinhardtii.
AB  - Ribulose-1,5-bisphosphate carboxylase/oxygenase is the key enzyme for
      photosynthesis. The wild-type and mutant (amino-acid substitutions in the
      catalytically important loop 6 region) enzymes from Chlamydomonas reinhardtii, a
      unicellular green alga, were crystallized. Wild-type, single-mutant (V331A) and
      two double-mutant (V331A/T342I and V331A/G344S) proteins were activated with
      cofactors CO2 and Mg2+, complexed with the substrate analog 2'-carboxyarabinitol
      1,5-bisphosphate, and crystallized in apparently isomorphous forms. Unit-cell
      determinations have been completed for three of the enzymes. They display
      orthorhombic symmetry with similar cell parameters: wild type a = 130.4, b = 203.
      3, c = 208.5 A; single mutant (V331A) a = 128.0, b = 203.0, c = 207. 0A; and
      double mutant (V331A/T342I) a = 130.0, b = 202.1, c = 209.7 A. Crystals of the
      wild-type and single-mutant (V331A) enzymes diffracted to approximately 2.8 A. A
      small crystal of the double-mutant (V331A/T342I) enzyme diffracted to
      approximately 6 A. A partial data set (68% complete) of the wild-type protein has
      been collected at room temperature to about 3.5 A.

PMID- 9761871
TI  - Characterization, crystallization and preliminary X-ray investigation of
      glyceraldehyde-3-phosphate dehydrogenase from the hyperthermophilic archaeon
      Sulfolobus solfataricus.
AB  - Recombinant Sulfolobus solfataricus glyceraldehyde-3-phosphate dehydrogenase has
      been purified and found to be a tetramer of 148 kDa. The enzyme shows dual
      cofactor specificity and uses NADP+ in preference to NAD+. The sequence has been
      compared with other GAPDH proteins including those from other archaeal sources.
      The purified protein has been crystallized from ammonium sulfate to produce
      crystals that diffract to 2.4 A with a space group of P43212 or P41212. A native
      data set has been collected to 2.4 A using synchrotron radiation and cryocooling.

PMID- 9761872
TI  - Crystallization and preliminary diffraction studies of pentaerythritol
      tetranitrate reductase from Enterobacter cloacae PB2.
AB  - Pentaerythritol tetranitrate (PETN) reductase of Enterobacter cloacae PB2, a
      flavoprotein involved in the biodegradation of the explosive PETN, ethylene
      glycol dinitrate (EGDN) and glycerol trinitrate (GTN), was purified from an
      overexpressing strain of E. coli and crystallized at 293 K using the sitting-drop
      vapour-diffusion method. Diffraction data can be seen at 1.8 A. The primitive
      orthorhombic cell has a monomer in the asymmetric unit. Preliminary molecular
      replacement calculations have been performed using a search model based on Old
      Yellow enzyme.

PMID- 9761873
TI  - Crystallization of 5-keto-4-deoxyuronate isomerase from Escherichia coli.
AB  - 5-Keto-4-deoxyuronate isomerase from Escherichia coli has been crystallized after
      partial purification. The isomerase was found to be enriched in preparations of
      an unrelated recombinant protein. Crystals of the isomerase were obtained from
      two different precipitants despite the fact that the recombinant protein
      represented roughly 90% of the total protein present. The crystals diffract to
      2.7 A resolution and are suitable for a structure determination. The role of the
      isomerase in E. coli is uncertain, as E. coli is not known to degrade the
      polysaccharides which are potential sources of 5-keto-4-deoxyuronate.

PMID- 9761874
TI  - Crystallization and preliminary X-ray studies of Pseudomonas putida histidine
      ammonium-lyase.
AB  - Histidine ammonium-lyase from P. putida was expressed in Escherichia coli,
      purified to homogeneity, and crystallized by the vapour-diffusion method using
      polyethylene glycol 3350 as the precipitant. The crystals, which diffract to at
      least 2.5 A resolution, exhibit the symmetry of space group P212121, with unit
      cell parameters a = 89.7, b = 138.2 and c = 164.8 A. The asymmetric unit contains
      a tetramer, and the crystals have a Vm value of 2.41 A3 Da-1.

PMID- 9761876
TI  - Crystallization and preliminary X-ray analysis of beta-glucan exohydrolase
      isoenzyme ExoI from barley (Hordeum vulgare).
AB  - Crystals of a beta-glucan exohydrolase purified from extracts of young barley
      seedlings have been obtained by vapour diffusion in the presence of ammonium
      sulfate and polyethylene glycol. The enzyme exhibits broad substrate specificity
      against (1,3)-, (1,3;1,4)- and (1,3;1,6)-beta-glucans, and related
      oligosaccharides. Crystal dimensions of up to 0.8 x 0.4 x 0.6 mm have been
      observed. The crystals belong to the tetragonal space group P41212 or P43212.
      Cell parameters are a = b = 102.1 and c = 184.5 A, and there appear to be eight
      molecules in the asymmetric unit. The crystals diffract to at least 2.2 A
      resolution using X-rays from a rotating-anode generator.

PMID- 9761875
TI  - Preliminary crystallographic investigations of recombinant GDP-4-keto-6-deoxy-D
      mannose epimerase/reductase from E. coli.
AB  - The GDP-4-keto-6-deoxy-D-mannose epimerase/reductase (GM_ER) isolated from E.
      coli has been overexpressed as a GST-fusion protein and purified to homogeneity.
      The enzyme, an NADP+(H)-binding homodimer of 70 kDa, is responsible for the
      production of GDP-L-fucose. GM_ER shows significant structural homology to the
      human erythrocyte protein FX, which is involved in blood-group glycoconjugate
      biosynthesis, displaying 3,5 epimerase/reductase activity on GDP-4-keto-6-deoxy-D
      mannose. GM_ER has been crystallized in a trigonal crystalline form, containing
      one molecule per asymmetric unit, suitable for high-resolution crystallographic
      investigations.

PMID- 9761877
TI  - Subcloning, crystallization and preliminary X-ray analysis of the signal receiver
      domain of ETR1, an ethylene receptor from Arabidopsis thaliana.
AB  - The signal receiver domain of ETR1, an ethylene receptor from Arabidopsis
      thaliana, has been subcloned and expressed in E. coli and purified by affinity
      chromatography. Crystals of both native and a selenomethionine-substituted form
      of the receiver domain have been obtained. Native crystals grew in 1.6 M Li2SO4
      and 0.1 M HEPES pH 7. 5 and once flash-frozen diffract to 2.1 A resolution. They
      belong to space group P41212 with unit-cell dimensions a = b = 48.4, c = 112.3 A.

PMID- 9761878
TI  - Preliminary X-ray analysis of a C2-like domain from protein kinase C-delta.
AB  - C2 domains are intracellular modules of approximately 130 residues that are found
      in many proteins involved in membrane trafficking and signal transduction. They
      are known to serve a variety of roles including binding ligands such as calcium,
      phospholipids and inositol polyphos-phates as well as interacting with larger
      macromolecules. Although originally identified in the Ca2+-dependent protein
      kinase C isoforms (PKC), initially no C2 domain was evident within the Ca2+
      independent isoenzymes. A recent study identified a divergent C2 domain in
      several novel, Ca2+-independent PKCs (delta, epsilon, eta and straight theta),
      located at their N-termini in a region previously referred to as a variable
      domain zero (Vo) [Ponting & Parker (1996). Protein Sci. 5, 2375-2390]. The
      functional importance of this domain in the context of the novel PKCs is at
      present not well understood though it has been implicated in substrate
      recognition. The expression, crystallization and preliminary crystallographic
      analysis of recombinant Vo domain (residues 1-123) from PKC-delta is reported
      here. Crystals were obtained from incomplete factorial screens after removal of
      the histidine tag used to aid purification. These crystals diffracted to Bragg
      spacings of approximately 3 A using a rotating-anode source and to 1.9 A using
      synchrotron radiation. The crystals have cell parameters of a = 60.7, b = 120.9
      and c = 40.7 A and systematic absences consistent with the orthorhombic space
      group P212121. To facilitate structure determination we have prepared,
      characterized and crystallized selenomethionine-substituted material.

PMID- 9761879
TI  - Crystallization and preliminary X-ray analysis of ferric enterobactin receptor
      FepA, an integral membrane protein from Escherichia coli.
AB  - Diffraction-quality crystals have been obtained of the integral membrane protein
      ferric enterobactin receptor (FepA) from the outer membrane of Escherichia coli.
      Crystals were grown using the zwitterionic detergent lauryldimethylamine oxide
      (LDAO), the precipitants polyethylene glycol (PEG) 1000 and sodium chloride, and
      the additive heptane-1,2,3-triol; they have the symmetry of the orthorhomic space
      group C2221 with a = 112.2, b = 137.2 and c = 135. 4 A and diffract to 2.5 A
      resolution. The crystals were flash-cooled and a preliminary data set was
      collected at 103 K. The crystals are suitable for three-dimensional structure
      analysis.

PMID- 9761880
TI  - Structure of type III antifreeze protein at 277 K.
AB  - Fish antifreeze proteins (AFP's) depress the freezing point of blood and other
      body fluids below that of the surrounding seawater by binding to and inhibiting
      the growth of seed ice crystals. The high-resolution crystal structure of type
      III AFP, determined at room temperature, reveals a remarkably flat surface
      containing most of the ice-binding residues [Jia et al. (1996). Nature (London),
      384, 285-288]. Since AFP's function at temperatures close to 273 K, it is
      important to know whether the structure determined at room temperature undergoes
      any change at much lower temperature. Therefore, type III AFP has been
      crystallized at 277 K and its structure determined. Although crystallization
      conditions at 277 K were similar to those at approximately 295 K, crystal growth
      took much longer at the lower temperature. Crystals grown at the two temperatures
      were isomorphous. Initial crystals appeared within 40-50 d and grew to their
      final size in about 8-12 months, instead of a couple of days at approximately 295
      K. The type III antifreeze protein structure from crystals grown at 277 K was
      essentially the same as that determined at approximately 295 K, with the
      exception of some minor changes in side-chain conformation. The result is an
      indication that temperature has a minimal effect on the structure of type III
      AFP, thus lending increased physiological validity to the room-temperature
      structure which was used for the initial ice-binding modelling.

PMID- 9761881
TI  - Protein crystals orientation in a magnetic field.
AB  - Nucleation and crystal growth of hen egg-white lysozyme, bovine pancreatic
      trypsin inhibitor and porcine pancreatic alpha-amylase were carried out in the
      presence of a magnetic field of 1.25 T produced by small permanent magnets.
      Crystals were oriented in the magnetic field, except when heterogeneous
      nucleation occurred. The orientation of protein crystals in the presence of a
      magnetic field can be attributed to the anisotropic diamagnetic susceptibility of
      proteins resulting from the large anisotropy of the alpha-helices due to the
      axial alignment of the peptide bonds.

PMID- 9761882
TI  - A general phasing algorithm for multiple MAD and MIR data.
AB  - A phasing algorithm is presented for combining multiple wavelength anomalous
      dispersion (MAD) data from multiple types of anomalous scatterers, either in the
      same or in different derivative crystals, as well as for combining MAD data with
      multiple isomorphous replacement (MIR) data from different derivative crystals. A
      heavy-atom phasing and refinement program originally written by Rossmann [(1967)
      HATOMLSQ program, Purdue University, West Lafayette, Indiana, USA] has been
      modified to refine the parameters that define the anomalous and isomorphous
      scatterers and to determine protein phases by using all MAD and MIR derivatives
      simultaneously. The technique allows for appropriate weighting of every data set,
      including the native data, which contains neither an anomalous nor an isomorphous
      component. This method is a generalization of currently used heavy-atom methods.
      Numerical tests are presented for different experimental scenarios, including a
      double MAD experiment on the same crystal (diffraction data at two absorption
      edges), combination of two MAD experiments on different crystals, and combination
      of MAD data with MIR data from multiple crystals. An appendix shows how the Karle
      equations used in MAD phasing can be reformulated as a particular case of this
      algorithm.

PMID- 9761883
TI  - Structure of balhimycin and its complex with solvent molecules.
AB  - Balhimycin is a naturally occurring glycopeptide antibiotic, related to
      vancomycin which acts by binding nascent bacterial cell-wall peptide ending in
      the sequence D-Ala-D-Ala. Crystals of balhimycin are monoclinic, space group P21,
      a = 20.48 (10), b = 43.93 (21), c = 27.76 (14) A, beta = 100.5 (5) degrees with
      four independent antibiotic molecules, three molecules of 2-methyl-2,4
      pentanediol, two citrate ions, three acetate ions and 127.5 water molecules in
      the asymmetric unit. With an asymmetric unit larger than those of the smallest
      proteins and a solvent content of about 32%, the crystals have similar
      diffraction properties to those of small proteins. 27387 unique reflections were
      collected using synchrotron radiation. The structure was solved by a standard
      protein technique, the molecular-replacement method, using ureido-balhimycin as
      search model. The anisotropic refinement against all F2 data between 0.96 and 45
      A converged to a conventional R value of 11.27% with R1= Sigma||Fo|
      |Fc||/Sigma|Fo| for the 24623 data with I > 2sigma(I) and 12.58% for all 27387
      data. The four monomers possess fairly similar conformations (r.m.s. deviation
      0.7 A). Two antibiotic molecules form a tight dimer with antiparallel hydrogen
      bonds between the peptide backbone as well as between the vancosamine residues
      and the peptide backbone. In each of the two dimers, one binding pocket is
      occupied by a citrate ion and the other by an acetate ion. The dimer units are
      linked in the crystal by hydrogen bonds to form infinite chains.

PMID- 9761884
TI  - Data compression for diffraction patterns.
AB  - Efficient coding (lossless) and compression (lossy) of diffraction patterns is
      important in protein crystallography experiments because of storage and
      transmission limitations. The goal is to reduce the bit-rate significantly while
      keeping diffraction peak intensity distortion at an acceptable level. This paper
      presents an overview of coding and compression techniques more or less adapted to
      such problems. A large part of this study is dedicated to time-frequency
      transform based compression algorithms and some of their extensions. Wavelet
      based software has been developed and tested. Results are compared with the
      discrete cosine transform (DCT) and other classical algorithms. These tools seem
      attractive and very promising for analyzing and compressing signals with
      singularities and transient phenomena such as diffraction peaks. Tests were
      performed on a standard protein crystallography data set coming from the CCD
      detector of D2AM beamline at the European Synchrotron Radiation Facility at
      Grenoble. These were compressed with DCT and wavelet-based algorithms. It appears
      that alterations of the result of the processing of restored images remain very
      weak for compression rates up to 10. These preliminary results indicate that the
      proposed wavelet method is a good standard technique for efficient compression of
      diffraction patterns.

PMID- 9761885
TI  - Stationary crystal diffraction with a monochromatic convergent X-ray source and
      application for macromolecular crystal data collection.
AB  - A diffraction geometry utilizing convergent X-rays from a polycapillary optic
      incident on a stationary crystal is described. A mathematical simulation of the
      resulting diffraction pattern (in terms of spot shape, position and intensity) is
      presented along with preliminary experimental results recorded from a lysozyme
      crystal. The effective source coverage factor is introduced to bring the
      reflection intensities onto the same scale. The feasibility of its application to
      macromolecular crystal data collection is discussed.

PMID- 9761886
TI  - Low-resolution structural characterization of the arginine repressor/activator
      from Bacillus subtilis: a combined X-ray crystallographic and electron
      microscopical approach.
AB  - Attempts to determine the X-ray crystal structure of the intact homohexameric
      arginine repressor/activator from B. subtilis have so far been unsuccessful. The
      major problem appears to be the lack of an isomorphous heavy-atom derivative with
      a manageable number of substitution sites. Here it is shown how electron
      microscopy of thin three-dimensional crystals, the same as those used for the X
      ray crystallographic studies, made it possible (i) to obtain experimental support
      for some conclusions drawn on the basis of X-ray data alone, (ii) to determine
      the low-resolution distribution of electron density in several different
      crystallographic projections, and (iii) to obtain a tentative low-resolution
      model of the whole hexamer.

PMID- 9761887
TI  - Effects of microheterogeneity in hen egg-white lysozyme crystallization.
AB  - In earlier sodium dodecylsulfate-polyacylamide gel electrophoresis (SDS-PAGE)
      studies it has been found that commonly utilized commercial hen egg-white
      lysozyme (HEWL) preparations contained 0.2-0.4 mol% covalently bound dimers. Here
      it is shown, using high-performance capillary electrophoresis (HPCE), that HEWL
      contains, in addition, two differently charged monomers in comparable amounts. To
      explore the origin of these microheterogeneous contaminants, purified HEWL
      (PHEWL) has been oxidized with hydrogen peroxide (0.0026-0.88 M) at various pH
      levels between 4.5 and 12.0. Optical densitometry of oxidized PHEWL (OHEWL) bands
      in SDS-PAGE gels shows that hydrogen peroxide at 0.88 M in acetate buffer pH 4.5
      increased the amount of dimers about sixfold over that in commercial HEWL. OHEWL
      had, in addition to one of the two monomer forms found in HEWL and PHEWL, three
      other differently charged monomer forms, each of them representing about 25% of
      the preparation. SDS-PAGE analysis of OHEWL yielded two closely spaced dimer
      bands with Mr = 28000 and 27500. In addition, larger HEWL oligomers with Mr = 1.7
      million and 320000 were detected by gel-filtration fast protein liquid
      chromatography with multiangle laser light scattering detection. Non-dissociating
      PAGE in large pore size gels at pH 4.5 confirmed the presence of these large
      oligomers in HEWL and OHEWL. Increased microheterogeneity resulted in substantial
      effects on crystal growth and nucleation rate. On addition of 10 microgram-1 mg
      ml-1 OHEWL to 32 mg ml-1 HEWL crystallizing solutions, both the number and size
      of forming crystals decreased roughly proportionally to the concentration of the
      added microheterogeneity. The same effect was observed in HEWL solutions on
      addition of 0.03-0.3 M hydrogen peroxide. Repartitioning of the dimer during
      crystallization at various temperatures between 277 and 293 K was analyzed by SDS
      PAGE. The crystals contained </= 25%(w/w) of the oligomers in the solution, with
      no apparent temperature dependence of the repartitioning.

PMID- 9761889
TI  - Error estimates of protein structure coordinates and deviations from standard
      geometry by full-matrix refinement of gammaB- and betaB2-crystallin.
AB  - Faster workstations with larger memories are making error estimation from full
      matrix least-squares refinement a more practicable technique in protein
      crystallography. Using minimum variance weighting, estimated standard deviations
      of atomic positions have been calculated for two eye lens proteins from the
      inverse of a least-squares normal matrix which was full with respect to the
      coordinate parameters. gammaB-crystallin, refined at 1.49 A yielded average
      errors in atomic positions which ranged from 0.05 A for main-chain atoms to 0.27
      A for unrestrained water molecules. The second structure used in this work was
      that of betaB2-crystallin refined at 2.1 A resolution where the corresponding
      average errors were 0.08 and 0.35 A, respectively. The relative errors in atomic
      positions are dependent on the number and kinds of restraints used in the
      refinements. It is also shown that minimum variance weighting leads to mean
      square deviations from target geometry in the refined structures which are
      smaller than the variances used in the distance weighting.

PMID- 9761888
TI  - Application of known triplet phases in the crystallographic study of bovine
      pancreatic trypsin inhibitor. II: study at 2.0 A resolution.
AB  - Direct methods strengthened by the application of about 130 triplet phases,
      assumed known with a mean error of about +/- 20 degrees, were used to re
      determine the structure of BPTI with data at 2.0 A resolution. The triplet phases
      served to shift the mean direction and enhance the concentration parameter in the
      corresponding Cochran distributions. These phases were used in combination with
      the partial structure extracted from successive density maps to control the
      gradual expansion and refinement of Fourier coefficients. Single phases were
      developed iteratively from tangent-formula estimation following the path of the
      convergence map. The a priori triplet phase information was sufficient to
      initiate solution of the structure at 2.0 A.

PMID- 9761890
TI  - Crystallographic study of azurin from Pseudomonas putida.
AB  - Azurin from Pseudomonas putida is a blue copper protein which functions as an
      electron carrier. Two crystal forms of azurin were grown, one in the presence and
      the other in the absence of zinc acetate; each belongs to space group P21 and
      contains two molecules per asymmetric unit. The zinc-free crystals have cell
      dimensions a = 43.25, b = 50.65, c = 54.60 A, beta = 107.79 degrees, while the
      crystals grown from zinc-containing solution have cell dimensions a = 40.76, b =
      51.22, c = 54.96 A, beta = 103.12 degrees. The latter crystals were found to have
      four zinc ions incorporated into the crystal lattice. Both crystal structures
      were solved by the molecular-replacement method using the program MERLOT. The
      search model was the structure of azurin from Alcaligenes denitrificans. The
      crystallographic R factor for native azurin is 0.169 (Rfree = 0. 257) from 8 to
      1.92 A resolution, while that for zinc azurin is 0. 181 (Rfree = 0.248) from 10
      to 1.6 A resolution; for each structure the root-mean-square deviation in bond
      lengths from ideal values is 0.007 A. In both crystal structures the Cu atom
      forms three strong bonds in the equatorial plane, two with Ndelta1 from His46 and
      His117, and one with the thiolate S atom of Cys112. Two longer axial approaches
      are made by the Sgamma from Met121 and the carbonyl O atom from Gly45. This
      results in a distorted trigonal bipyramidal co-ordination around the Cu atom. It
      further confirms the presence of a weak fifth bond to the copper in P. putida
      azurin, as with other azurin structures described at high resolution. The Ndelta1
      atom of His35 is protonated, as it is in the low-pH form of azurin from
      Pseudomonas aeruginosa but unlike the low-pH form of the azurins from Alcaligenes
      denitrificans or Alcaligenes xylosoxidans. In each crystal form the two molecules
      of azurin in the asymmetric unit are related by a local twofold axis and form a
      dimer stabilized by the interaction of a pair of hydrophobic patches surrounding
      the partially exposed His117 side chain. In the other known azurin crystal
      structures, analogous dimer formation is observed, but with different relative
      orientations of the molecules. The four zinc ions introduced during
      crystallization of zinc azurin are bound to the protein and participate in five-
      and sixfold ligand coordination with no affect on the copper binding site. The
      zinc ligands are Ndelta from His, carboxylate O atoms from Asp and Glu, Ogamma
      from Ser and water molecules. One of the zinc ions, located on a non
      crystallographic twofold axis, links the dimers of the asymmetric unit into
      continuous chains parallel to the crystallographic (-101) direction and is
      primarily responsible for the altered unit-cell parameters. Two of the other zinc
      ions bind to His83, one in each molecule.

PMID- 9761891
TI  - Crystallization of NAD+-dependent phenylalanine dehydrogenase from Nocardia
      sp239.
AB  - The NAD+-dependent phenylalanine dehydrogenase from Nocardia sp239 has been
      crystallized by the hanging-drop method of vapour diffusion using ammonium
      sulfate as the precipitant. Two crystal forms were obtained in the presence and
      absence of the enzyme substrates phenylpyruvic acid or phenylalanine and its
      coenzyme NADH. Crystals of the native protein belong to the hexagonal system,
      with the space group being one of the enantiomorphic pair P6122 or P6522. The
      cell dimensions are a = b = 111.0, c = 174.5 A, alpha = beta = 90 and gamma = 120
      degrees. Crystals grown from the protein co-crystallized with its substrates all
      belong to the trigonal system, space group P3121 or P3221, with unit-cell
      dimensions of a = b = 88.1, c = 112.6 A, alpha = beta = 90 and gamma = 120
      degrees. Preliminary protein-sequencing experiments have established that this
      enzyme is related to the octameric PheDH's which are members of the wider
      superfamily of amino-acid dehydrogenases. However, gel-filtration studies suggest
      that this enzyme is active as a monomer. The full determination of the three
      dimensional structure of this phenylalanine dehydrogenase will add to the
      understanding of the molecular basis of the differential substrate specificity
      within this enzyme superfamily. In turn this will contribute to the rational
      design of an amino-acid dehydrogenase which could be used for the diagnosis of
      phenylketonuria and for the chiral synthesis of high-value pharmaceuticals.

PMID- 9761892
TI  - Crystallization and preliminary X-ray analysis of tetanus neurotoxin C fragment.
AB  - Two crystal forms of recombinant tetanus neurotoxin C fragment have been
      obtained. The C fragment corresponds to the C-terminal 451 amino-acid residues of
      tetanus neurotoxin and is the subunit responsible for receptor binding by the
      toxin. Both forms belong to space group P212121. Form I has unit-cell dimensions
      of a = 71.3, b = 79.7, c = 94.0 A and produces thin plate crystals. Form II has
      unit-cell dimensions of a = 67.4, b = 79.7, c = 91.1 A and produces thick rod
      shaped crystals. Diffraction data to 2.6 A have been collected from form II
      crystals.

PMID- 9761893
TI  - Crystallization of the alpha-hemolysin heptamer solubilized in decyldimethyl- and
      decyldiethylphosphine oxide.
AB  - Crystals of the alpha-hemolysin heptamer, a transmembrane pore-forming toxin from
      Staphylococcus aureus, have been grown using the nonionic detergents n
      decyldimethyl- and n-decyldiethylphosphine oxide, phosphorus homologs of the
      ionic amine oxide detergents. Five crystal forms were obtained, one of which
      diffracted X-rays to 3 A resolution. This crystal form displayed elements of
      pseudo mm symmetry in screened precession photographs yet it was triclinic with
      unit-cell dimensions a = 173, b = 173, c = 102 A, alpha = 92.6, beta = 94.8,
      gamma = 90.2 degrees.

PMID- 9761894
TI  - Crystallization and preliminary analysis of chondroitinase AC from Flavobacterium
      heparinum.
AB  - Chondroitinase AC (E.C. 4.2.2.5) overexpressed in its host, Flavobacterium
      heparinum, was crystallized by vapor diffusion using polyethylene glycol methyl
      ether as precipitant. It crystallizes in the space group P43212 or its
      enantiomorph with a = b = 87.1 and c = 193.1 A and one molecule in the asymmetric
      unit. Crystals diffract to a maximum of 2.5 A resolution on a rotating-anode
      source. Screening for heavy-atom derivatives identified a lead compound that
      binds to a single site on the protein. Further screening is in progress.

PMID- 9761895
TI  - Crystallization and preliminary X-ray diffraction studies of phospho
      adenylylsulfate (PAPS) reductase from E. coli.
AB  - PAPS reductase from E. coli is involved in sulfur metabolism and catalyses the
      reduction of phospho-adenylyl-sulfate (PAPS) to sulfite. The protein has been
      cloned, overexpressed and purified from E. coli. Crystallization experiments
      resulted in crystals suitable for X-ray diffraction. The crystals belong to the
      orthorhombic space group C2221 with cell dimensions a = 81.9, b = 97.4, c = 109.5
      A, and contain one molecule per asymmetric unit. At cryogenic (100 K)
      temperatures the crystals diffract to a resolution limit of 2.7 A using a
      rotating anode and to 2.0 A at a synchrotron source.

PMID- 9761896
TI  - Crystallization and preliminary X-ray diffraction analysis of cytochrome c' from
      Rubrivivax gelatinosus at 1.3 A resolution.
AB  - Cytochrome c' from the purple non-sulfur phototrophic bacterium Rubrivivax
      gelatinosus has been crystallized by vapour diffusion at pH 5, 6.3 and 8, in
      sodium acetate, sodium citrate, and Tris-HCl buffers, respectively. Crystals
      grown at pH 5 and 6.3 diffract, respectively, to 2.0 A (298 K) and 1.4 A (100 K)
      using synchrotron radiation. Data up to 1.3 A resolution with 99.8% completeness
      were collected at 100 K on a crystal grown at pH 8. The space group is P3121 or
      P3221, and the unit-cell parameters are a = b = 69.63, c = 123.63 A.

PMID- 9761897
TI  - 1.2 A refinement of the Kunitz-type domain from the alpha3 chain of human type VI
      collagen.
AB  - The recombinant Kunitz-type domain (C5) of human collagen alpha3(VI) chain was
      previously described at 1.6 A resolution at room temperature. By changing the
      crystallization conditions and using synchrotron radiation, we are able to record
      diffraction data to 1.2 A resolution for crystals of the same space group at 291
      K. The protein-water-ion model has been refined anisotropically against these new
      data using the program SHELXL93; the results converged to an R factor of 15.0%,
      with all data between 7 and 1.2 A. The final electron-density map reveals a clear
      chain tracing with a few disordered residues and five residues out of 58 that
      present alternate conformations. The Cys14-Cys38 bond presents the less
      frequently observed left-hand conformation (chi1 = -60 degrees). The solvent
      molecules and a phosphate ion are well ordered with an average B of 38 A2. The
      high-resolution structure reveals the N and C termini which were missing from the
      1.6 A structure.

PMID- 9761898
TI  - 1.85 A resolution structure of the zinc (II) beta-lactamase from Bacillus cereus.
AB  - Class B beta-lactamases are wide spectrum enzymes which require bivalent metal
      ions for activity. The structure of the class B zinc-ion-dependent beta-lactamase
      from Bacillus cereus (BCII) has been refined at 1.85 A resolution using data
      collected on cryocooled crystals (100 K). The enzyme from B. cereus has a
      molecular mass of 24 946 Da and is folded into a beta-sandwich structure with
      helices on the external faces. The active site is located in a groove running
      between the two beta-sheets [Carfi et al. (1995). EMBO J. 14, 4914-4921]. The 100
      K high-resolution BCII structure shows one fully and one partially occupied zinc
      sites. The zinc ion in the fully occupied site (the catalytic zinc) is
      coordinated by three histidines and one water molecule. The second zinc ion is at
      3.7 A from the first one and is coordinated by one histidine, one cysteine, one
      aspartate and one unknown molecule (most likely a carbonate ion). In the B.
      cereus zinc beta-lactamase the affinity for the second metal-ion is low at the pH
      of crystallization (Kd = 25 mM, 293 K; [Baldwin et al. (1978). Biochem. J. 175,
      441-447] and the dissociation constant of the second zinc ion was thus apparently
      decreased at the cryogenic temperature. In addition, the structure of the apo
      enzyme was determined at 2.5 A resolution. The removal of the zinc ion by
      chelating agents causes small changes in the active-site environment.

PMID- 9761899
TI  - Molecular replacement using DNA helical symmetry.
AB  - The efficiency of molecular-replacement methods in the structure analysis of B
      DNA is markedly increased if a knowledge of the structural properties and helical
      symmetry of B-DNA is incorporated into molecular-replacement procedures. The
      separation of the most significant or most robust parameters, such as the
      location of helices in the unit cell, from the less well defined parameters, such
      as rotation around the helix axis, further improves the reliability of molecular
      replacement and avoids frameshift errors in the positioning of the model. This
      approach has been applied successfully to solve novel structures of four B-DNA
      decamers in various space groups.

PMID- 9761900
TI  - Structure of the complex of bovine pancreatic phospholipase A2 with a transition
      state analogue.
AB  - The 1.89 A resolution structure of the complex of bovine pancreatic phospholipase
      A2 (PLA2) with the transition-state analogue L-1-O-octyl-2-heptylphosphonyl-sn
      glycero-3-phosphoethanolamine (TSA) has been determined. The crystal of the
      complex is trigonal, space group P3121, a = b = 46.58 and c = 102.91 A and
      isomorphous to the native recombinant wild type (WT). The structure was refined
      to a final crystallographic R value of 18.0% including 957 protein atoms, 88
      water molecules, one calcium ion and all 31 non-H atoms of the inhibitor at 1.89
      A resolution. In all, 7 726 reflections [F>2sigma(F)] were used between 8.0 and
      1.89 A resolution. The inhibitor is deeply locked into the active-site cleft and
      coordinates to the calcium ion by displacing the two water molecules in the
      calcium pentagonal bipyramid by the anionic O atoms of the phosphate and
      phosphonate group. The hydroxyl group of Tyr69 hydrogen bonds to the second
      anionic O atom of the phosphate group while that of the phosphonate group
      replaces the third water, 'catalytic' water, which forms a hydrogen bond to
      Ndelta1 of His48. The fourth water which also shares Ndelta1 of His48 is
      displaced by the steric hinderance of the inhibitor. The fifth conserved
      structural water is still present in the active site and forms a network of
      hydrogen bonds with the surrounding residues. The structure is compared to the
      other known TSA-PLA2 complexes.

PMID- 9761901
TI  - 1.72 A resolution refinement of the trigonal form of bovine pancreatic
      phospholipase A2.
AB  - The trigonal crystal structure of the recombinant bovine pancreatic phospholipase
      A2 has been re-refined at a slightly higher resolution (1.72 A). The crystals are
      trigonal, space group P3121, unit-cell parameters a = b = 46.78 and c = 102.89 A
      and are isomorphous to the previous structure. The structure was refined to a
      final crystallographic R value of 19.5% (Rfree = 28.4%) using 10 531 reflections.
      A total of 106 solvent molecules were included in the refinement compared with
      the earlier refinement which contains only 85 water molecules and 8 925
      reflections at 1.8 A resolution. The root-mean-square deviation from the ideal
      bond lengths and bond angles is considerably better in the present refinement.
      The active site is extended ( approximately 14 A) from Ala1 to the calcium. The
      three catalytic residues (Asp99, His48 and the catalytic water) are connected by
      the conserved structural water and the N-terminal Ala1 on one side, and by the
      calcium through an equatorial water on the other. The water molecules play a role
      in the activity of the enzyme PLA2. The Ala1 end of the extended active site
      performs the activation of the phospholid membranes while the opposite end
      performs the hydrolysis of the monomeric phospholids.

PMID- 9761902
TI  - Structure of azurin I from the denitrifying bacterium Alcaligenes xylosoxidans
      NCIMB 11015 at 2.45 A resolution.
AB  - Azurin I from Alcaligenes xylosoxidans NCIMB 11015 (AzN-I) was crystallized by
      using PEG 4000 as a precipitant. The crystals belong to the monoclinic crystal
      system and have a space group C2 with the unit-cell parameters of a = 130.67, b =
      54.26, c = 74.55 A, and beta = 95.99 degrees. The structure of AzN-I has been
      solved by the molecular replacement method. Azurin II from the same bacterium
      (AzN-II) was chosen as the initial structural model. The final crystallographic R
      value is 17.3% and free R value is 23.6% for 10958 reflections at a resolution of
      2.45 A. The root-mean-square deviations for main-chain atoms range between 0.19
      and 0.26 A among the four independent molecules in the asymmetric unit. The Cu
      atom is coordinated to Ndelta of His46 and His117 at 2.0 (1) and 1.9 (1) A, and
      to Sgamma of Cys112 at 2.2 (1) A, while the carbonyl O atom of Gly45 and Sdelta
      of Met121 coordinate axially to Cu atom at 2.5 (1) and 3.1 (1) A, respectively.
      The Cu-N and Cu-S distances of AzN-I are quite similar to those of AzN-II,
      however, the Cu-SO (Gly45) bond length in AzN-I is 0.25 A shorter than the
      counterpart in AzN-II. The results have been used to discuss the differences in
      the spectra of these two proteins.

PMID- 9761903
TI  - Human carboxyhemoglobin at 2.2 A resolution: structure and solvent comparisons of
      R-state, R2-state and T-state hemoglobins.
AB  - The three-dimensional structure and associated solvent of human carboxyhemoglobin
      at 2.2 A resolution are compared with other R-state and T-state human hemoglobin
      structures. The crystal form is isomorphous with that of the 2.7 A structure of
      carboxyhemoglobin reported earlier [Baldwin (1980). J. Mol. Biol. 136, 103-128],
      whose coordinates were used as a starting model, and with the 2.2 A structure
      described in an earlier report [Derewenda et al. (1990). J. Mol. Biol. 211, 515
      519]. During the course of the refinement, a natural mutation of the alpha
      subunit, A53S, was discovered that forms a new crystal contact through a bridging
      water molecule. The protein structure shows a significant difference between the
      alpha and beta heme geometries, with Fe-C-O angles of 125 and 162 degrees,
      respectively. The carboxyhemoglobin is compared with other fully ligated R-state
      human hemoglobins [Baldwin (1980). J. Mol. Biol. 136, 103-128; Shaanan (1983). J.
      Mol. Biol. 195, 419-422] with the R2-state hemoglobin [Silva et al. (1992). J.
      Biol. Chem. 267, 17248-17256] and with T-state deoxyhemoglobin [Fronticelli et
      al. (1994). J. Biol. Chem. 269, 23965-23969]. The structure is similar to the
      earlier reported R-state structures, but there are differences in many side-chain
      conformations, the associated water structure and the presence and the position
      of a phosphate ion. The quaternary changes between the R-state carboxyhemoglobin
      and the R2-state and T-state structures are in general consistent with those
      reported in the earlier structures. The location of 238 water molecules and a
      phosphate ion in the carboxyhemoglobin structure allows the first comparison of
      the solvent structures of the R-state and T-state structures. Distinctive
      hydration patterns for each of the quaternary structures are observed, but a
      number of conserved water molecule binding sites are found that are independent
      of the conformational state of the protein.

PMID- 9761904
TI  - Structure refinement against synchrotron Laue data: strategies for data
      collection and reduction.
AB  - The synchrotron Laue technique has been applied to high-resolution structure
      refinement of the ribotoxin, restrictocin [Yang & Moffat (1996). Structure, 4,
      837-852]. By employing carefully designed data-collection strategies and the data
      reduction algorithms incorporated in the software system LaueView [Ren & Moffat
      (1995a). J. Appl. Cryst. 28, 461-481; Ren & Moffat (1995b). J. Appl. Cryst. 28,
      482-493], a set of high-resolution Laue data with a completeness and accuracy
      comparable to excellent monochromatic data was obtained. Through detailed
      comparison with the monochromatic data and electron-density maps derived from the
      Laue data, optimum data-collection and reduction strategies were identified and
      the application of Laue diffraction techniques to conventional crystallographic
      refinement was demonstrated.

PMID- 9761905
TI  - Structure analysis of two CheY mutants: importance of the hydrogen-bond
      contribution to protein stability.
AB  - The crystal structures of two double mutants (F14N/V21T and F14N/V86T) of the
      signal transduction protein CheY have been determined to a resolution of 2.4 and
      2.2 A, respectively. The structures were solved by molecular replacement and
      refined to final R values of 18.4 and 19.2%, respectively. Together with urea
      denaturation experiments the structures have been used to analyse the effects of
      mutations where hydrophobic residues are replaced by residues capable of
      establishing hydrogen bonds. The large increase in stabilization (-12.1 kJ mol-1)
      of the mutation Phe14Asn arises from two factors: a reverse hydrophobic effect
      and the formation of a good N-cap at alpha-helix 1. In addition, a forward
      backward hydrogen-bonding pattern, resembling an N-capping box and involving
      Asn14 and Arg18, has been found. The two Val to Thr mutations at the hydrophobic
      core have different thermodynamic effects: the mutation Val21Thr does not affect
      the stability of the protein while the mutation Val86Thr causes a small
      destabilization of 1.7 kJ mol-1. At site 21 a backward side chain-to-backbone
      hydrogen bond is formed inside alpha-helix 1 with the carbonyl O atom of the i -
      4 residue without movement of the mutated side chain. The destabilizing effect of
      introducing a polar group in the core is efficiently compensated for by the
      formation of an extra hydrogen bond. At site 86 the new Ogamma atom escapes from
      the hydrophobic environment by a chi1 rotation into an adjacent hydrophilic
      cavity to form a new hydrogen bond. In this case the isosteric Val to Thr
      substitution is disruptive but the loss in stabilization energy is partly
      compensated by the formation of a hydrogen bond. The two crystal structures
      described in this work underline the significance of the hydrogen-bond component
      to protein stability.

PMID- 9761907
TI  - Determination of the relative precision of atoms in a macromolecular structure.
AB  - Several real-space indices and temperature factors are compared with respect to
      their correlation with atomic positional error and their ability to indicate
      atoms and residues with the worst of subtle errors. The best index, rED, is a
      correlation coefficient between model and map electron densities, similar to one
      proposed earlier, but incorporating two improvements. Firstly, resolution is
      accounted for explicitly by calculating the model electron density by Fourier
      transformation of resolution-truncated scattering factors. Secondly, the
      deviation between model and map electron densities is assigned to neighboring
      atoms according to their contribution to the electron density of each grid point.
      With maps of various qualities, rED is the single index with best correlation to
      atomic error with grouped or individual atoms, and it is the most reliable
      indicator of poor residues. With poorer omit maps, imprecision of individual
      atoms is best diagnosed by a combination of low rED or high B factor. With the
      improved methods, 60-70% of the least precise atoms can detected in a fully
      refined structure. Similarly, 40-80% of the least precise atoms of an unrefined
      model can be detected by comparison with an isomorphous replacement map. This is
      useful in assessing and improving the quality of a model, but not sufficient to
      confidently validate all atoms of a structure at sub-atomic resolution.

PMID- 9761908
TI  - A translation-function approach for heavy-atom location in macromolecular
      crystallography.
AB  - A method for locating heavy atoms in the unit cell of macromolecular crystals by
      a full-symmetry translation function is described. The approach has been
      implemented in the program TRAHALO and tested on experimental isomorphous and
      anomalous data.

PMID- 9761909
TI  - Crystallization and preliminary X-ray investigation of the complex of RNase Sa
      with wild-type barstar.
AB  - RNase Sa, an extracellular ribonuclease produced by Streptomyces aureofaciens, is
      inhibited by barstar, the natural protein inhibitor of barnase, the ribonuclease
      of Bacillus amyloliquefaciens. The complex of RNase Sa with wild-type barstar was
      crystallized by hanging-drop vapour diffusion. It was shown by sodium dodecyl
      sulfate polyacrylamide gel electrophoresis that RNase Sa and barstar are present
      in equimolar proportions in the crystals. The crystals are in the hexagonal space
      group P65 with unit cell dimensions a = b = 56.95, c = 135.8 A. They diffract to
      1.7 A resolution at the DESY synchronton source. The asymmetric unit contains one
      molecule of the complex.

PMID- 9761910
TI  - Crystallization of two hCG-specific monoclonal antibody fragments.
AB  - The Fab fragments of two monoclonal antibodies (Fab3A2, Fab6A) raised against
      epitopes of human chorionic gonadotrophin (hCG) have been crystallized using the
      vapour-diffusion technique. The Fab3A2 antibody recognises an epitope on the C
      terminal peptide of the beta-subunit and the Fab6A a conformational epitope of
      hCG. Both Fab crystals grow as hexagonal rods from ammonium sulfate solutions.
      The Fab3A2 crystals belong to space group P3121 with a = b = 74.84, c = 198.2 A
      and diffract to 1.33 A at the ESRF. The Fab6A crystals are in the space group
      P3221 with a = b = 129.53, c = 74.40 A and diffract to 2.7 A at the Daresbury
      SRS. One Fab molecule per asymmetric unit is present in both crystals.

PMID- 9761911
TI  - Crystallization of the alanine dehydrogenase from Phormidium lapideum.
AB  - Amino-acid dehydrogenases catalyse the interconversion of their respective amino
      acids to the corresponding keto acid, with concomitant reduction of NAD or NADP.
      The enzymes phenylalanine, glutamate, leucine and valine dehydrogenase all share
      a similar three-dimensional subunit structure and a high degree of sequence
      similarity, indicating that they belong to an enzyme superfamily related by
      divergent evolution. In contrast, alanine dehydrogenase shows no sequence
      similarity with any of these enzymes despite catalysing a reaction with the same
      chemistry and thus it is predicted that it possesses a different three
      dimensional structure. The alanine dehydrogenase from Phormidium lapideum has
      been crystallized in space group R32, cell dimensions a = b = 123.1 and c = 184.8
      A, with a monomer in the asymmetric unit. The structure determination of this
      enzyme will shed light on how nature has evolved two different systems to carry
      out the same reaction.

PMID- 9761912
TI  - Crystallization and preliminary high-resolution X-ray diffraction analysis of
      native and beta-mercaptoethanol-inhibited urease from Bacillus pasteurii.
AB  - Hexagonal crystals of urease from Bacillus pasteurii have been obtained by vapour
      diffusion at 293 K in 20 mM Tris-HCl, neutral pH, containing 50 mM Na2SO3.
      Isomorphous crystals of urease inhibited with beta-mercaptoethanol were also
      obtained by including 4 mM of the inhibitor in the enzyme solution. Crystals of
      the native and inhibited enzyme diffract respectively to 2.00 A (96.7%
      completeness) and to 1.65 A (98.7% completeness) using synchrotron X-ray
      cryogenic (100 K) conditions. The space group is P6322 for both forms, and the
      unit-cell parameters are a = b = 131.36, c = 189. 76 A for native urease and a =
      b = 131.34, c = 190.01 A for inhibited urease. Under the same conditions, single
      crystals of B. pasteurii urease inhibited with acetohydroxamic acid, cisteamine,
      and phenylphosphorodiamidate were also obtained.

PMID- 9761913
TI  - Crystallization and preliminary X-ray diffraction studies of homoserine
      dehydrogenase from Saccharomyces cerevisiae.
AB  - Recombinant homoserine dehydrogenase from Saccharomyces cerevisiae has been
      crystallized in three different forms. Crystals of the apo-enzyme belong to the
      tetragonal space group P4 and have unit-cell-dimensions a = b = 130 and c = 240
      A. The resolution limit for these crystals is 3.9 A. Crystals of homoserine
      dehydrogenase grown in the presence of the co-factor NAD+ have the tetragonal
      space group P41212 or its enantiomorph P43212. The unit-cell dimensions for these
      crystals are a = b = 80.4 and c = 250.2 A, and the observed resolution limit is
      2.2 A. Protein crystals grown in the presence of the product L-homoserine and the
      inert NAD+ analogue 3-aminopyridine adenine dinucleotide belong to the monoclinic
      space group P21 with unit-cell parameters a = 58.8, b = 104.2, c = 120.7 A, beta
      = 91.9 degrees. This last crystal form has a diffraction limit of 2.7 A
      resolution.

PMID- 9761914
TI  - Preliminary X-ray crystallographic analysis of a novel maltogenic amylase from
      Bacillus stearothermophilus ET1.
AB  - A novel maltogenic amylase from Bacillus stearothermophilus ET1, which has a dual
      activity of alpha-1,4- and alpha-1,6-glycosidic bond cleavages and alpha-1,6
      glycosidic bond formation, was crystallized by using the hanging-drop vapor
      diffusion method. The best crystals were obtained by employing a high
      concentration of protein (56 mg ml-1) and a precipitant containing 22% glycerol,
      1.6 M ammonium sulfate in 0.1 M Tris-HCl (pH 8.5). Native diffraction data to
      2.66 A resolution have been obtained from crystals flash-frozen at 110 K. The
      crystals belong to the space group P212121 with unit-cell dimensions of a =
      77.62, b = 121.23, c = 244. 29 A, and contain three or four protomers per
      asymmetric unit. Structure determination by multiple isomorphous replacement is
      in progress.

PMID- 9761915
TI  - Crystallization and preliminary X-ray analysis of a member of a new family of
      pectate lyases, PeIL from Erwinia chrysanthemi.
AB  - PeIL, a pectate lyase (E.C. 4.2.2.9) from E. chrysanthemi 3937 that is not
      homologous to the lyases with known structures, has been purified and
      crystallized by the hanging-drop method using a variety of organic solvents as
      precipitant. Elongated lathes grown from poly(ethylene glycol) plus isopropanol
      belong to the space group P212121 with cell dimensions a = 55.5, b = 58.2, c =
      16.4 A with a single molecule in the asymmetric unit. Although complete data sets
      have been collected to 2.3 A resolution, these crystals diffract to at least 1.9
      A resolution and are suitable for structure determination. Chunky plates grown
      using other organic solvents as the precipitant diffracted to 3 A resolution and
      were partially characterized as a second orthorhombic crystal form with space
      group P21212 and cell dimensions a = 119.1, b = 140.5 and c = 105.4 A, suggesting
      four molecules in the asymmetric unit.

PMID- 9761916
TI  - Crystallization of an intact GST-estrogen receptor hormone binding domain fusion
      protein.
AB  - Crystals of an intact GST-estrogen receptor hormone binding domain fusion protein
      have been grown from solutions of MPD. The crystals grew as clusters of thin
      plates and needles of maximum dimensions 100 x 20 x 1 micrometer but were
      unsuitable for X-ray diffraction analysis. However, examination by electron
      microscopy shows an ordered lattice in which the protein molecules are clearly
      visible. Image analysis of electron micrographs of the protein crystals revealed
      electron stain-excluding density which showed a two-domain trimeric structure in
      projection, with each molecule of dimensions 12.0 x 5.0 nm diameter. The use of
      GST-fusion proteins in crystallisation are discussed.

PMID- 9761917
TI  - Crystallization of the NADP-dependent beta-keto acyl carrier protein reductase
      from Escherichia coli.
AB  - The NADP-dependent beta-keto acyl carrier protein reductase (BKR) from E. coli
      has been crystallized by the hanging-drop method of vapour diffusion using
      poly(ethylene glycol) of average molecular weight 1450. The crystals belong to
      the hexagonal space group P6122 or P6522 with unit-cell dimensions a = b = 67.8,
      c = 355.8 A. Calculated values for Vm and consideration of the packing suggest
      that the asymmetric unit contains a dimer. BKR catalyses the first reductive step
      in the elongation cycle of fatty-acid biosynthesis. It shares extensive sequence
      homology with the enzyme which catalyzes the second reductive step in the cycle,
      enoyl acyl carrier protein reductase (ENR), and thus provides an opportunity to
      study the evolution of enzyme function in a metabolic pathway. The structure
      determination will permit the analysis of the molecular basis of its catalytic
      mechanism and substrate specificity.

PMID- 9761918
TI  - Crystallization and preliminary X-ray diffraction studies of the catalytic core
      of acetyl xylan esterase from Trichoderma reesei.
AB  - Acetyl xylan esterase is involved in the biodegradation of hemicellulose. It
      cleaves O-acetyl groups from xylan, which is the most abundant hemicellulose in
      nature. The catalytic core of acetyl xylan esterase from T. reesei has been
      crystallized and X-ray diffraction data at 2.3 A collected. The crystal belongs
      to the triclinic space group P1 with unit-cell parameters a = 50.3, b = 62. 1, c
      = 40.0 A, alpha = 110.1, beta = 113.6 and gamma = 97.9 degrees. The asymmetric
      unit contains two molecules.

PMID- 9761919
TI  - Crystallization and preliminary diffraction studies of the extracellular region
      of human p58 killer cell inhibitory receptor (KIR2).
AB  - Molecules of the human killer cell inhibitory receptor (KIR) family, which belong
      to the immunoglobulin superfamily (IgSF), are expressed on the surface of natural
      killer (NK) cells and some subsets of T cells. These receptors function to
      mediate the inhibition or activation of cytotoxic activity by recognizing HLA
      class I molecules on the target cell. The extracellular region of a p58 KIR
      specific for HLA-Cw1,3,7 (KIR2) has been overproduced in Escherichia coli and
      purified. The recombinant KIR2 has been crystallized in 9-10% poly(ethylene
      glycol) methyl ether (average Mr = 8000), 50mM HEPES, 8% ethylene glycol, 0.5%
      octyl-beta-glucoside, pH 7.5, at 294 K using the sitting-drop vapour-diffusion
      method. Preliminary X-ray diffraction studies reveal the space group to be
      hexagonal (P6122 or P6522) with lattice constants a = b = 95.3, c = 130.8 A. A
      native data set (3 A resolution) has been collected at the Photon Factory (lambda
      = 1.0 A).

PMID- 9761920
TI  - Crystallization and preliminary X-ray studies of hORF6, a novel human antioxidant
      enzyme.
AB  - HORF6 is a member of the novel antioxidant enzyme family found in humans. A
      recombinant form of hORF6 expressed and purified from E. coli has been
      crystallized by the hanging-drop method using various PEG's as precipitating
      agents. HORF6 crystallizes in two different monoclinic space groups, P21 and C2.
      The P21 crystals have unit-cell dimensions of a = 47.85, b = 75.17, c = 63.30 A
      and beta = 110.21 degrees and contain two monomers per asymmetric unit, while the
      C2 crystals have unit-cell dimensions of a = 165.27, b = 95.44, c = 166.44 A and
      beta = 128.97 degrees and contain more than six monomers per asymmetric unit. The
      P21 crystals with the smaller unit cell diffract X-rays better and behave well
      for the X-ray analysis. A native data set from a single crystal of the P21 space
      group gas been collected to 2.0 A resolution.

PMID- 9761921
TI  - Crystallization and preliminary X-ray diffraction studies of E. coli
      porphobilinogen synthase and its heavy-atom derivatives.
AB  - Porphobilinogen synthase (PBGS) catalyzes the condensation of two identical
      substrate molecules, 5-aminolevulinic acid (ALA), in an asymmetric manner to form
      porphobilinogen. E. coli PBGS is an homooctameric enzyme. The number of active
      sites is not clear, but each subunit binds one ZnII ion and one MgII ion.
      Diffraction-quality crystals of native E. coli PBGS have been obtained, and unit
      cell dimensions (a = 130.8, c = 144.0 A) are reported. These crystals diffract to
      about 3.0 A resolution.

PMID- 9761922
TI  - Preliminary X-ray crystallographic analysis of Bowman-Birk trypsin inhibitor from
      barley seeds.
AB  - Bowman-Birk trypsin inhibitor from barley seeds has been crystallized at room
      temperature using polyethylene glycol as precipitant. The crystal is tetragonal,
      belonging to the space group P41212 (or P43212), with unit cell parameters of a =
      b = 62.48 and c = 94.63 A. The asymmetric unit contains one molecule of Bowman
      Birk trypsin inhibitor with corresponding crystal volume per protein mass (Vm) of
      2.89 A3 Da-1 and the solvent content of 57% by volume. The crystals diffract to
      at least 1.9 A Bragg spacing upon exposure to synchrotron X-rays. X-ray data to
      1.9 A have been collected from a native crystal.

PMID- 9761923
TI  - Crystallization and preliminary X-ray studies on the hyperstable 3
      isopropylmalate dehydrogenase from the thermoacidophilic archaeon Sulfolobus sp.
      strain 7.
AB  - 3-Isopropylmalate dehydrogenase from the thermoacidophilic archaeon, Sulfolobus
      sp. strain 7, has been crystallized by the vapor-diffusion method. The crystals
      were grown from a solution containing ammonium sulfate, 2-methyl-2,4-pentanediol
      and magnesium chloride. The crystallization requires 2-methyl-2,4-pentanediol to
      avoid twinning of the crystals. The crystal belongs to the orthorhombic system
      with the space group P2221 and unit-cell dimensions a = 67.9, b = 93.3 and c =
      134.1 A.

PMID- 9761924
TI  - Purification, crystallization and preliminary X-ray diffraction studies on the
      thermostable catechol 2,3-dioxygenase of Bacillus stearothermophilus expressed in
      Escherichia coli.
AB  - The thermostable catechol 2,3-dioxygenase of Bacillus stearothermophilus has been
      crystallized. The crystal is probably in the space group I222 with unit-cell
      dimensions of a = 70.87, b = 74.60 and c = 133.69 A. A native data set has been
      collected with a completeness of 96% at 2.22 A resolution and an Rmerge value of
      0.091.

PMID- 9761925
TI  - Crystallization and preliminary X-ray analysis of thiaminase I from Bacillus
      thiaminolyticus: space group change upon freezing of crystals.
AB  - Thiaminase I (Mr = 42 100) from B. thiaminolyticus, expressed in E. coli, has
      been crystallized by the vapor-diffusion method. Three crystal forms, two of
      which grew from 0.1 M sodium acetate (pH = 4.6), 0.2 M ammonium sulfate and
      30%(w/v) PEG 2000, have been examined by X-ray analysis. One crystal form
      diffracted to 2.5 A at room temperature, was orthorhombic, and had unit-cell
      edges of a = 87.7, b = 120.5 and c = 76.7 A with space group P212121. A self
      Patterson map showed a strong peak indicating noncrystallographic translational
      pseudosymmetry with (u, v, w) = (0.03, 0.0, 0.5). When these crystals were frozen
      at liquid-nitrogen temperatures, a second crystal form was observed which had
      unit-cell dimensions a = 85.5, b = 117.5 and c = 36.6 A with space group P21212.
      A third crystal form grew from 0.1 M Tris (pH = 8.5), 0.2 M sodium acetate
      trihydrate and 28%(w/v) PEG 6000 to produce orthorhombic crystals of space group
      P212121 with cell edges of a = 114.4, b = 123.1 and c = 92.5 A.

PMID- 9761926
TI  - Expression, purification, crystallization and crystallographic characterization
      of the human MHC class I related protein MICA.
AB  - Crystals of the human MHC-encoded molecule MICA, a homologue of MHC class I
      proteins, have been grown in hanging-drop vapor-diffusion trials using ammonium
      sulfate as a precipitating agent with recombinant protein expressed in a
      baculovirus-based system. Cryo-preserved crystals of MICA belong to the cubic
      space group F4132 with lattice constants a = b = c = 260.7 A and diffract to a
      resolution limit of 3.0 A when cryo-preserved. These crystals do not diffract
      when handled conventionally.

PMID- 9761927
TI  - Preliminary X-ray analysis of a new crystal form of the vanadium-dependent
      bromoperoxidase from Corallina officinalis.
AB  - A new crystal form of the vanadium-dependent bromoperoxidase from Corallina
      officinalis has been obtained. The crystals exhibit a 'teardrop' morphology and
      are grown from 2 M ammonium dihydrogen phosphate pH and diffract to beyond 1.7 A
      resolution. They are in tetragonal space group P4222 with unit-cell dimensions of
      a = b = 201.9, c = 178.19 A, alpha = beta = gamma = 90 degrees. A 2.3 A
      resolution native data set has been collected at the Hamburg Synchrotron. A
      mercury derivative data set has also been collected, and the heavy-atom positions
      have been determined. The self-rotation function and the positions of the heavy
      atoms are consistent with the molecule being a dodecamer with local 23 symmetry.

PMID- 9761928
TI  - Expression, crystallization and preliminary X-ray analysis of ligand-free human
      glutathione S-transferase M2-2.
AB  - Human glutathione-S-transferase M2-2 (hGSTM2-2) was expressed in Escherichia coli
      and purified by GSH-affinity chromatography. The recombinant enzyme and the
      protein isolated from human tissue were indistinguishable based on
      physicochemical, enzymatic and immunological criteria. The catalytically active
      dimeric hGSTM2-2 was crystallized without GSH or other active-site ligands in two
      crystal forms. Diffraction from form A crystals extends to 2.5 A and is
      consistent with the space group P21 (a = 53.9, b = 81.5, c = 55.6 A, beta =
      109.26 A) with two monomers in the asymmetric unit. Diffraction from form B
      crystals extends to 3 A and is consistent with a space group P212121 (a = 57.2, b
      = 80.7, c = 225.9 A) with two dimers in the asymmetric unit. This is the first
      report of ligand-free mu-class GST crystals, and a comparison with liganded
      complexes will provide insight into the structural consequences of substrate
      binding which are thought to be important for catalysis.

PMID- 9761929
TI  - Enhanced electron-density envelopes by extended solvent definition.
AB  - Extended delineation of water molecules, monitored using Rfree values, afforded
      considerable improvement in quality of electron-density maps for structure
      determination of mammalian class I and E. coli class II aldolases. Augmented
      solvent definition results in an additional decrease in Rfree values of 3-4% and
      is reflected in significantly enhanced electron-density envelopes enabling
      tracing of amino-acid sequences through regions of otherwise discontinuous or
      weak electron density.

PMID- 9761930
TI  - Polymorphous crystallization and diffraction of threonine deaminase from
      Escherichia coli.
AB  - The biosynthetic threonine deaminase from Escherichia coli, an allosteric
      tetramer with key regulatory functions, has been crystallized in several crystal
      forms. Two distinct forms, both belonging to either space group P3121 or P3221,
      with different sized asymmetric units that both contain a tetramer, grow under
      identical conditions. Diffraction data sets to 2.8 A resolution (native) and 2. 9
      A resolution (isomorphous uranyl derivative) have been collected from a third
      crystal form in space group I222.

PMID- 9761931
TI  - An improved procedure for the preparation of X-ray diffraction-quality crystals
      of cytochrome p450cam.
AB  - A procedure for the crystallization of recombinant cytochrome P450cam has been
      developed which avoids the difficulties inherent in the glass-capillary free
      interface diffusion method reported previously. The surface mutation, Cys334-
      >Ala (C334A), originally designed to prevent dimer formation and thus improve
      routine handling of the enzyme, facilitates crystallization by the hanging-drop
      vapour-diffusion technique. Crystals of (C334A)P450cam grow within 48 h and
      diffract to beyond 1.2 A at 100 K in-house on a Siemens multiwire area detector.
      Data have been collected from the camphor-bound form to 1.35 A.

PMID- 9761932
TI  - Crystallographic studies of casein kinase I delta toward a structural
      understanding of auto-inhibition.
AB  - A recombinant form of mammalian casein kinase I delta (CKIdelta) containing the
      catalytic domain and an auto-inhibitory domain was expressed in Escherichia coli,
      purified and crystallized. X-ray data were collected to 2.4 A resolution, and the
      crystals belong to space group C2221. Molecular replacement using the structure
      of the catalytic domain of CKIdelta yielded strong electron density for residues
      in the model, but no interpretable density was found for the inhibitory domain. A
      conserved intermolecular contact suggests the formation of dimers which would
      inhibit the activity of this protein kinase.

PMID- 9761933
TI  - Expression, purification, crystallization and preliminary X-ray diffraction
      analysis of human uroporphyrinogen decarboxylase.
AB  - A recombinant human uroporphyrinogen decarboxylase (E.C. 4.1.1.37, UROD) has been
      expressed in Escherichia coli and purified to homogeneity. Crystals grew by the
      hanging-drop vapor-diffusion technique from a starting solution containing 1.5 mg
      ml-1 protein. The crystals belong to the trigonal space group P3121 or its
      enantiomer P3221 and diffract to 3 A resolution. The unit-cell parameters are a =
      b = 103.4, c = 75.7 A and gamma = 120 degrees. The asymmetric unit contains one
      molecule. Preliminary structural predictions suggest for the protein a TIM-barrel
      type tertiary structure.

PMID- 9761934
TI  - A flash-annealing technique to improve diffraction limits and lower mosaicity in
      crystals of glycerol kinase.
AB  - A flash-annealing method has been developed that increases the diffraction
      limits, and simultaneously decreases the mosaicity of glycerol kinase crystals.
      This technique utilizes brief thawing and rapid freezing cycles of the crystal in
      the cold nitrogen stream. The effective resolution limits increased almost by 0.8
      A, from 3.6 to 2.8 A, and mosaicity values halved.

PMID- 9761935
TI  - Benefits of pharmacological knowledge in the design and monitoring of cancer
      chemotherapy.
AB  - Prescribing chemotherapy is a difficult task, because of drug resistance, which
      prevents all tumors to respond to a given protocol and because of drug toxicity,
      which is generally unavoidable but which must be limited to acceptable levels.
      The therapeutic window of anticancer drugs is very narrow and clinicians have to
      try to optimize the individual doses and schedules of the drugs to be
      administered. They can rely upon simple anthropometric features, such as body
      weight or surface area; they can also take into account the physiological status
      of the patient: age, liver and kidney function, genetic characteristics of drug
      metabolism, etc. The best way for dose adaptation lies in the establishment of
      pharmacokinetic/pharmacodynamic relationships, i.e., between the behavior of a
      drug in the body and its efficacy and toxicity. When it is established that the
      optimal effect of a drug is related to a given parameter, such as the area under
      the curve plotting plasma concentration vs. time (AUC), it becomes possible to
      administer the drug with the dose allowing to obtain the target parameter value.
      Individual dose adaptation can be achieved thanks to the study of the
      pharmacokinetics of a test dose preceding that of the therapeutic dose, or by the
      measure of drug plasma levels, either at steady state during a protracted
      infusion, or from cycle to cycle during repetitive protocols. Population analysis
      now allows the adaptation of anticancer drug dosing from a minimum knowledge of
      individual pharmacokinetic features, together with other characteristics of the
      patients such as age, gender or physiological functions.

PMID- 9761936
TI  - BMD188, A novel hydroxamic acid compound, demonstrates potent anti-prostate
      cancer effects in vitro and in vivo by inducing apoptosis: requirements for
      mitochondria, reactive oxygen species, and proteases.
AB  - A newly synthesized cyclic hydroxamic acid compound, BMD188 [cis-1-hydroxy-4-(1
      naphthyl)-6-octylpiperidine-2-one], was found to induce the apoptotic death of
      cultured prostate cancer cells by activating caspase-3. Orally administered
      BMD188 significantly inhibited the primary growth of prostate cancer cells
      (Du145) orthotopically implanted into SCID mice. Mechanistic studies indicated
      that BMD188 did not alter the protein levels of several Bcl-2 family members. In
      contrast, the BMD188 effect required three essential factors: reactive oxygen
      species (ROS), the mitochondrial respiratory chain function, and proteases.
      First, the apoptosis-inducing effect of BMD188 could be blocked by ROS scavengers
      such as Desferal. Second, both BMD188-induced PARP cleavage as well as PC3 cell
      apoptosis could be dramatically inhibited by several complex-specific
      mitochondrial respiration blockers. The involvement of mitochondria was also
      supported by the observations that BMD188 dramatically altered the mitochondrial
      distribution and morphology without affecting the cellular ATP levels. Finally,
      the apoptosis-inducing effect of BMD188 in PC3 cells could be significantly
      inhibited by serine protease inhibitors (TPCK and TLCK) as well as by caspase
      inhibitors (zVAD-fmk and DEVD-CHO). Collectively, the present study suggests that
      BMD188 and its analogs may find clinical applications in the treatment of
      prostate cancer patients by inducing apoptotic death of prostate cancer cells.

PMID- 9761937
TI  - Combined in vitro effect of marijuana and retrovirus on the activity of mouse
      natural killer cells.
AB  - Both marijuana and retroviruses impair natural killer (NK) cell functions. No
      data on their simulataneous effects are available. Similarities to human AIDS
      induced early by Friend leukemia complex (FLC) and its replication competent
      helper Rowson-Parr virus (RPV) provides a mouse model to study drug-virus action.
      Leukemia susceptible BALB/c and resistant C57BL/6 mice were infected, then at
      time intervals their nylon wool-separated splenocytes were exposed to
      tetrahydrocannabinol (THC) for 3h. Natural killer (NK) cell activity against Yac
      1 cells was assayed by 51Cr-release for 4 and 18h. Recovery of splenocytes was
      found to be suppressed by FLC, but in BALB/c only by RPV. After a transient
      enhancement in C57BL/6 by FLC, NK cell activity of both mice became suppressed
      early (2 to 4 days), normalized subsequently and enhanced late (11 to 14 days)
      postinfection. A moderate increase in BALB/c, no change in C57BL/6 were induced
      by low (1-2.5 microgram/ml) THC doses. NK cell activity of BALB/c became
      suppressed exponentially by higher (5-10 microgrtam/ ml) THC doses in 18h as
      compared to 4h assays, while its proportional and moderate impairment was seen in
      C57BL/6. The magnitude of NK cell activity of infected mice was determined by
      THC: enhancement or impairment followed those of untreated, infected
      counterparts, but on the level of THC-treated cells. Low doses hardly, high doses
      additively influenced NK cells of infected BALB/c. THC hardly affected very early
      and late enhancement in NK cell activiy of FLC infected C57BL/6, but augmented
      RPV induced suppression late in 18h assays. Genetic factors similar to endotoxin
      resistance, altered cytokine profile might determine these effects. Similar
      phenomena in humans might result in earlier manifestation of AIDS.

PMID- 9761938
TI  - EBER oligonucleotide RNA in situ hybridization in EBV associated neoplasms.
AB  - In virus associated diseases identification of viruses in cells can contribute to
      the understanding of the pathogenesis and may also help to establish the
      diagnosis. In the present communication, the effects of the microwave
      pretreatment (MWP) and that of the proteinase-K enzymatic predigestion (PKD) on
      EBER RNA oligonucleotide in situ hybridization (EBER-RNA-ISH) (EBER: Epstein-Barr
      Encoded-(Early)-RNA) were studied. The efficacy of two EBV detecting methods,
      latent membrane protein-1 (LMP-1) immunohistochemistry and EBER-RNA-ISH were also
      compared. Our results show that microwave pretreatment enhances the intensity of
      the ISH signals and preserves significantly better the structure of the tissues
      compared with enzymatic predigestion. EBER-RNA-ISH, mainly in the nasopharyngeal
      carcinoma cases, showed a more frequent positivity than the immunohistochemical
      reaction for LMP-1, however in case of the Warthin's tumor only the LMP-1 protein
      was expressed.

PMID- 9761939
TI  - Fibrinolytic activity of earthworms extract (G-90) on lysis of fibrin clots
      originated from the venous blood of patients with malignant tumors.
AB  - u-PA is secreted by the most malignant tumors. As a response to u-PA synthesis
      surrounding cells synthetize inhibitors of plasminogen activators for tissue
      protection. Plasminogen activators were found also in earthworm tissue. From the
      tissue homogenate of earthworm Eisenia foetida the glycolipoprotein mixture named
      G-90 was isolated. It contains two serine proteases (P I, P II) with fibrinolytic
      and anticoagulative activities. The fibrinolytic activity of G-90, P I and P II
      was tested in an in vitro euglobulinic test applied to fibrin clot from blood
      plasma of patients suffered from malignant tumors. G-90 and above-mentioned
      proteases applied in this study showed euglobulinic time proportionally with the
      concentrations of added substances. The influence of G-90 on the fibrinolysis
      rate does not depend only on its concentration, but depends too on histological
      type of tissue (organ) where the malignant tumors are located. Enzyme P I and P
      II do not show this activity.

PMID- 9761940
TI  - Corpus amylaceum (polyglucosan body) in the peripheral olfactory system.
AB  - Peripheral part of the olfactory system (bulb and tract) was investigated for the
      occurrence of corpus amylaceum (CA) (polyglucosan body) in 296 (281 pathological
      and 15 control cases) autopsied human brains. No significant differences were
      found in the incidence between the various age groups above 40 years or between
      different disease groups and the controls. The predominance of CA in the
      olfactory tract and its loose correlation with age at this localization over 40
      years of age could be resulted by various factors, including the extremely rich
      astrocytic and capillary network in the intermediate zone, and the proximity of
      the olfactory tract to the external environment, which may result in the
      protective role of CA. The role of stress was proved by the HSP-60 positivity of
      CA.

PMID- 9761941
TI  - A new method to localize acid phosphatase using the confocal laser-scanning
      microscope.
AB  - The aim of the study was to work out a technique for the detection of acid
      phosphatase enzyme activity by confocal laser-scanning microscope using the
      histochemical acid phosphatase detection method (after Barka and Anderson 1962,
      modified by Bowen and Lewis 1985) routinely used for light microscopy. The
      density and the distribution of enzyme reaction product is dependent on the
      incubation time, as shown by different confocal images or ELISA reader. The
      inhibition of the enzyme activity with metal ions shows the same profile known
      from the literature. This staining method seems to be useful to demonstrate
      subcellular distribution of the enzyme in the lysosomes and in the Golgi
      apparatus.

PMID- 9761942
TI  - A novel in vitro system to study extravasated tumor cell-induced angiogenesis.
AB  - Angiogenesis, the formation of new blood vessels from preexisting ones, is a
      fundamental stage in the metastatic pathway. For the primary tumor, this
      neovascularization provides nutrients and oxygen as well as a route by which
      metastatic tumor cells gain access to the circulatory system. Among these
      metastatic tumor cells, there are subgroups of cells that express an angiogenesis
      inducing cells phenotype (AICs) as well as others that do not. Tumor cells not
      expressing the angiogenesis-inducing cells phenotype (non-AICs) invade new
      tissues and remain as dormant micrometastases unless they accompany AICs. Thus,
      either alone or with non-AICs, angiogenesis-inducing cells form rapidly growing,
      clinically detectable metastases. Much of the current research in this area is
      concentrated on the vascularization of primary tumors, but the regulation of
      angiogenesis by extravasating or invading tumor cells has not being extensively
      studied. We have developed a working model, which demonstrates that human
      metastatic prostate cancer cells (PC-3) appear to induce human vascular
      endothelial cells (HUVECs) to translocate across a Matrigel-coated 8 mm membrane.
      The parameters of this model (i.e. pore size, seeding-cell density, seeding
      times) were established using highly invasive murine melanoma cells (B16F10)
      seeded on murine microvascular endothelial cells (CD3). We have further modified
      our model in order to include a host compartment made of collagen gel, in order
      to mimic the in vivo site of metastases-induced angiogenesis.

PMID- 9761944
TI  - Phenotypes of T cells in the gut.

PMID- 9761946
TI  - Mucosal T cell-epithelial cell interactions.

PMID- 9761945
TI  - T-cell receptor usage in the intestine.

PMID- 9761947
TI  - Beta 7 integrins and their ligands in lymphocyte migration to the gut.

PMID- 9761943
TI  - Tumor and endothelial cell invasion of basement membranes. The matrigel
      chemoinvasion assay as a tool for dissecting molecular mechanisms.
AB  - The spread of cancer cells from a primary tumor to distant organs is the major
      cause of death of cancer patients. Metastatic lesions are often resistent to
      cancer therapy because of the progressive phenotypic changes that they have
      undergone. Several genetic and epigenetic factors, both in the cell and in the
      host, contribute to the development of tumor progression towards metastases. In
      this review we will analyze the steps involved in tumor metastases, which can be
      potential targets for anti-metastatic therapy. One of the most critical events in
      cancer metastasis is the invasion of basement membranes. An assay which we
      developed over ten years ago, the matrigel "chemoinvasion" assay, has been a
      useful tool for studying the mechanisms involved in tumor and endothelial cell
      invasion of basement membranes and for the screening of anti-invasive agents.
      Here we will describe the assay and review some of the major results obtained
      with it.

PMID- 9761948
TI  - Gamma delta T cells: bodyguards and/or sleepers in the gut.

PMID- 9761950
TI  - Lamina propria T cells.

PMID- 9761949
TI  - Thymus-independent development of gut T cells.

PMID- 9761951
TI  - T cells in mouse models of gut inflammation.

PMID- 9761952
TI  - T-cell response to orally administered antigens and its role in the treatment of
      autoimmune diseases.

PMID- 9761953
TI  - T-cell response to inhaled antigen.

PMID- 9761955
TI  - Th1 and Th2 cells and immunity to intestinal helminths.

PMID- 9761954
TI  - Role of T cells in asthma.

PMID- 9761956
TI  - T cell and cytokine regulation of the IgA response.

PMID- 9761957
TI  - Introduction to cell volume regulatory mechanisms.

PMID- 9761958
TI  - Cell volume-regulated cation channels.

PMID- 9761959
TI  - Cell volume-sensitive chloride channels.

PMID- 9761960
TI  - Mechanisms of osmolyte release.

PMID- 9761961
TI  - Sensors and signal transduction in the activation of cell volume regulatory ion
      transport systems.

PMID- 9761962
TI  - Activation of protein kinases upon volume changes: role in cellular homeostasis.

PMID- 9761964
TI  - Approaches to identifying cell volume-regulated genes.

PMID- 9761963
TI  - Intracellular signaling in response to osmotic stress.

PMID- 9761965
TI  - The cytoskeleton in cell volume regulation.

PMID- 9761966
TI  - Cell volume regulatory ion transport in cell migration.

PMID- 9761968
TI  - Cellular osmoregulation in kidney medulla.

PMID- 9761967
TI  - Cell volume in cell proliferation and apoptotic cell death.

PMID- 9761969
TI  - Osmoregulation of liver cell function: signalling, osmolytes and cell
      heterogeneity.

PMID- 9761970
TI  - Volume regulation and 'cross-talk' in sodium-absorbing epithelial cells.

PMID- 9761972
TI  - Swelling-activated release of excitatory amino acids in the brain: relevance for
      pathophysiology.

PMID- 9761971
TI  - Pathophysiology of abnormal cell volume in human red cells.

PMID- 9761973
TI  - Coronary artery disease in dialysis patients.

PMID- 9761974
TI  - Bacterial infections after renal transplantation.

PMID- 9761975
TI  - The use of mycophenolate mofetil (Cellcept) in renal transplantation.

PMID- 9761976
TI  - The impact of residual renal function on the adequacy of peritoneal dialysis.

PMID- 9761977
TI  - Tacrolimus in kidney transplantation.

PMID- 9761978
TI  - Renal disease in the elderly.

PMID- 9761979
TI  - Hypertension in the transplanted patient.

PMID- 9761982
TI  - Beobachtungsstudien im Rahmen eines naturheilkundlichen Klinikverbunds. teil i:
      methoden und ubersicht der ergebnisse in den beteiligten kliniken.

PMID- 9761981
TI  - Saliva Collection with Salivettes(R) Is a Sympathetic Stimulus.

PMID- 9761980
TI  - Morbidity and mortality on maintenance haemodialysis.

PMID- 9761985
TI  - Ozontherapy as a Possible Biological Response Modifier in Cancer.

PMID- 9761983
TI  - Methodological Standards and Problems in Preclinical Homoeopathic Potency
      Research.

PMID- 9761986
TI  - Der aktuelle Stand der Ozontherapie - Empirie und Grundlagenforschung.

PMID- 9761987
TI  - Zu den Arbeiten von Bocci und Beck et al.

PMID- 9761988
TI  - Antwort der Autoren.

PMID- 9761989
TI  - Beobachtungsstudien im Rahmen eines naturheilkundlichen Klinikverbunds.

PMID- 9761990
TI  - Naturheilverfahren bei einer Patientin mit chronischer Bronchitis und asthmoider
      Reaktion.

PMID- 9761991
TI  - Ein auditorisches neurophysiologisches Interventionsverfahren bei Migrane - Eine
      offene Anwendungsbeobachtung.

PMID- 9761992
TI  - Die Wirkung wassriger Torffraktionen auf die kontraktile Aktivitat von glatter
      Muskulatur.

PMID- 9761993
TI  - In-vivo-und In-vitro-Versuche zur Erforschung der Wirkungsentfaltung von
      Homoopathika.

PMID- 9761994
TI  - Beobachtungsstudien im Rahmen eines naturheilkundlichen Klinikverbunds.

PMID- 9761995
TI  - Zum Dynamikbegriff Hahnemanns.

PMID- 9761996
TI  - Apoptose-Induktion and DNA-Stabilisierung durch Viscum album L.

PMID- 9761998
TI  - Chronisch-entzundliche Darmerkrankungen (Colitis ulcerosa; Enteritis regionalis
      Crohn): Atiologie und Therapieergebnisse unter Anwendung der bioenergetischen
      Funktionsdiagnostik und der Magnetfrequenzakupunktur.

PMID- 9761997
TI  - Versuche zur Detektion von Wirkungsunterschieden zwischen Potenz und
      gleichkonzentrierter Verdunnung.

PMID- 9761999
TI  - Beobachtungsstudien im Rahmen eines naturheilkundlichen Klinikverbunds.

PMID- 9762000
TI  - Major Multi-National Pharmaceutical Companies and Complementary Medicine.

PMID- 9762001
TI  - Craniofacial growth and dental maturation in short children born small for
      gestational age: effect of growth hormone treatment. Own observations and review
      of the literature.
AB  - Short children born small for gestational age (SGA) may be candidates for
      treatment with growth hormone (GH). We examined craniofacial growth and dental
      maturation in a cohort of short SGA children. The general growth failure of these
      children is reflected to a differential extent within the craniofacial complex.
      As a group, these children have a small retrognathic face with a relatively
      increased lower anterior face height; in contrast to skeletal maturation, dental
      age is not delayed. GH treatment in short prepubertal SGA children leads to
      craniofacial catch-up growth, which is particularly pronounced in regions where
      interstitial cartilage is involved, the result being that the facial profile
      becomes less convex; dental maturation does not appear to be influenced by GH
      treatment. In conclusion, in short SGA children, GH treatment does not only
      result in an increase of body stature but also in a trend towards normalization
      of craniofacial growth and this without notable advancement of dental maturation.

PMID- 9762002
TI  - Potential role for growth hormone in human lactation insufficiency.
AB  - In order to evaluate the galactopoietic response to rhGH in mothers of normal
      babies with idiopathic lactation insufficiency arising in the early postpartum
      period, we performed a preliminary, randomised, single blind trial of 3 different
      doses of hGH: either 0.05, 0.1, or 0.2 IU/kg/day to a maximum of 16 IU/day, for 7
      days. Total 24-hour milk production was determined in each mother 1 day prior to
      initiating therapy and on the last day of therapy. Milk production rose by 36.0
      +/- 12.6% in the group receiving 0.2 IU/kg/day (n = 6) but by only 4.7 +/- 9.7%,
      (p < 0.04) in the combined lower dose group (n = 10). In conclusion, these data
      suggest that moderate dose hGH therapy in mothers with lactation insufficiency
      can improve galactopoiesis.

PMID- 9762003
TI  - Congenital hypothyroidism screening in the West Bank: a test case for screening
      in developing regions.
AB  - Screening for congenital hypothyroidism (CH) among the Arab population of the
      West Bank began in May 1987 as part of the neonatal screening program in Israel.
      In the West Bank many infants are born at home or are released from the hospital
      on the 1st day after birth and thus cannot be screened. However, we tried to
      reach the infants before the age of 1 month at the maternal and child health
      centers, where they receive immunization. In this screening program, 64% of the
      infants were sampled by the 1st week and 93% by 3 weeks of life. In contrast to
      the screening in Israel, where thyroxine determination is followed by thyroid
      stimulating hormone measurement, in the West Bank thyroid-stimulating hormone was
      tested first in order to decrease the recall rates. From June 1990 to February
      1994, 49,694 infants were screened in the West Bank, of whom 24 with CH were
      detected (an incidence of 1:2,070). From January 1987 to February 1994, 28,938
      infants were screened in East Jerusalem, of whom 20 with CH were detected
      (incidence 1:1,447). There were differences between the incidence rates in the
      various districts. The incidence rates were higher than those reported from
      industrialized countries, but similar to those found in Saudi Arabia. This may be
      due to the high degree of consanguineous marriages among Arab populations and to
      environmental factors. In conclusion, in spite of the many difficulties, both
      practical and political, CH screening in the West Bank is feasible. Although
      screening all newborns shortly after birth is not possible, this study shows that
      a high percentage of them can be screened at a time when they can still be
      effectively treated. Our results could be used in due time as a baseline for a
      future independent screening program.

PMID- 9762004
TI  - Steroid receptor mRNA levels in human corpus luteum.
AB  - To understand the biology of sex steroids in the human corpus luteum, the
      expression of estrogen receptor alpha, progesterone receptor, and androgen
      receptor mRNA levels was determined by semiquantitative reverse-transcription
      polymerase chain reaction-Southern blot analysis. Expression of all receptor
      mRNAs was detected in all samples analyzed. Each steroid receptor mRNA level was
      significantly lower (p < 0.05) during the late secretory phase than that during
      the early or the mid-secretory phase of the endometrium. These findings support
      the concept of a local role for sex steroids in modulating the function and life
      span of the human corpus luteum.

PMID- 9762005
TI  - Does a positive oestrogen feedback on the hypothalamic-pituitary axis exist
      concurrently with a defective testosterone feedback in Klinefelter's syndrome?
AB  - The oestrogen provocation and GnRH challenge tests were carried out in 5 subjects
      with Klinefelter's syndrome who had no history of previous hormonal therapy. The
      oestrogen provocation test consisted of an intramuscular injection of 10 mg of
      oestradiol valerate and blood samples were collected daily from day 0 to day 5.
      In 2 subjects, three GnRH challenge tests were carried out before (day 0) and on
      days 2 and 4 after the intramuscular injection of oestradiol valerate. During
      each GnRH challenge test, 7 blood samples were collected at 30-min intervals, 30
      min and immediately before and for 150 min after the bolus dose of GnRH. Plasma
      concentrations of FSH, LH, testosterone and oestradiol were measured by
      established radioimmunoassays. Plasma levels of oestradiol rose significantly a
      day following the intramuscular injection of 10 mg of oestradiol valerate,
      reaching a peak on day 2 and then falling significantly to lower levels by days 4
      and 5, although these levels were still significantly higher than the
      corresponding baseline levels. In the presence of high levels of oestradiol, the
      high basal levels of FSH were significantly suppressed, and remained suppressed
      throughout the 5 days of the study. LH, on the other hand, had a biphasic
      response; an initial significant suppression by day 1 persisting to day 3, but by
      days 4 and 5 a rebound in basal LH levels was noted. However, the levels on day 5
      were not significantly higher than baseline levels. The pituitary responsiveness
      as far as the LH and FSH secretions were concerned reflected the baseline levels.
      The results of the present study refuted the claim that a positive oestrogen
      feedback exists in men including Klinefelter's syndrome as a result of the
      removal of or reduced testosterone. In addition, the attenuated testosterone
      feedback in Klinefelter's syndrome is responsible for the greatly amplified
      pituitary responsiveness to the trophic action of GnRH and this, in part, may be
      responsible for the elevated levels of FSH and LH seen in such patients.

PMID- 9762006
TI  - Plasma levels of insulin-like growth factor (IGF)-I, IGF-II and IGF-binding
      protein-3 in the evaluation of childhood growth hormone deficiency.
AB  - BACKGROUND: Traditionally, measurement of plasma IGF-I and more recently of IGFBP
      3 are used to distinguish GHD from idiopathic short stature in slowly growing
      children, using a single blood sample. In earlier studies it was claimed that
      IGFBP-3 was superior to IGF-I, but more recently doubts around this claim have
      arisen. The role of serum IGF-II has never been studied extensively. On
      theoretical grounds, it can also be hypothesized that molar ratios of these
      peptides might be of additional value. DESIGN: Retrospective, multicentre, cohort
      study. PATIENTS: 96 children evaluated for short stature. METHODS: Serum IGF-I,
      IGF-II, IGFBP-3 and various molar ratios were, after correction for age and sex
      using SD scores, compared to the maximum serum GH peak after two standard
      provocation tests using four different methods (t-test, chi2, likelihood ratios
      and ROC curves). In addition, the correlations between these parameters and the
      short-term (1 year) and long-term (3 years) response to GH therapy were
      calculated. RESULTS: IGF-I performed better than IGFBP-3, but the best results
      were achieved by the molar ratio IGF-I:IGF-II. However, IGFBP-3 correlated better
      with the short-term response to GH therapy than IGF-I or the ratios, and none of
      the parameters investigated was found to be related to the response of long-term
      GH therapy.

PMID- 9762007
TI  - Regulation of PTP-1 and insulin receptor kinase by fractions from cinnamon:
      implications for cinnamon regulation of insulin signalling.
AB  - Bioactive compound(s) extracted from cinnamon potentiate insulin activity, as
      measured by glucose oxidation in the rat epididymal fat cell assay. Wortmannin, a
      potent PI 3'-kinase inhibitor, decreases the biological response to insulin and
      bioactive compound(s) from cinnamon similarly, indicating that cinnamon is
      affecting an element(s) upstream of PI 3'-kinase. Enzyme studies done in vitro
      show that the bioactive compound(s) can stimulate autophosphorylation of a
      truncated form of the insulin receptor and can inhibit PTP-1, a rat homolog of a
      tyrosine phosphatase (PTP-1B) that inactivates the insulin receptor. No
      inhibition was found with alkaline phosphate or calcineurin suggesting that the
      active material is not a general phosphatase inhibitor. It is suggested, then,
      that a cinnamon compound(s), like insulin, affects protein phosphorylation
      dephosphorylation reactions in the intact adipocyte. Bioactive cinnamon compounds
      may find further use in studies of insulin resistance in adult-onset diabetes.

PMID- 9762008
TI  - Insulin-like growth factor I receptors are expressed by the enteroendocrine cell
      line STC-1: relationship with proliferation and cholecystokinin expression.
AB  - Receptors for insulin-like growth factors (IGF-I and IGF-II) are expressed in
      mammalian intestinal epithelium. No information on the presence of IGF receptors
      in intestinal endocrine cells is available. We tested for IGF-I receptors the
      endocrine cell line STC-1, which synthesizes and processes cholecystokinin (CCK)
      among other peptides, and assessed the effects of IGF-I on cell growth and CCK
      content. Cell monolayers in serum-free culture medium specifically bound
      [125I]IGF-I. Scatchard analysis was consistent with a single class of high
      affinity binding sites (KD = 0.91 nM; Bmax = 4,700 sites/cell). In competitive
      binding assays, unlabeled IGF-I, IGF-II and insulin displaced in a dose-dependent
      manner [125I]IGF-I binding with the following potencies (KI): IGF-I (0.74 nM) >
      IGF-II (3 nM) >> insulin (1 microM). Affinity cross-linking with [125I]IGF-I
      using disuccinimidyl suberate and SDS-PAGE under reducing conditions yielded a
      polypeptide band with apparent Mr 130,000, consistent with the alpha-subunit of
      the IGF-I receptor. IGF-I and IGF-II (0.3-30 nM) dose-dependently stimulated
      [3H]thymidine incorporation, with a maximal response of 110% above basal. IGF-II
      was approximately 10-fold less potent than IGF-I, suggesting a mediation through
      IGF-I receptors. In addition, the numbers of cells treated with 3 nM IGF-I
      amounted to 116, 130 and 159% of control values after 1, 2 and 4 days of
      incubation, respectively (p < 0.05). A significant increase in the cell CCK
      contents was observed after a 48-hour exposure to 3 or 30 nM IGF-I. These results
      demonstrate IGF-I receptor expression by the enteroendocrine cell line STC-1. IGF
      I stimulates proliferation in short-term experiments, and increases intracellular
      levels of CCK.

PMID- 9762009
TI  - Hypergonadotropic hypogonadism in a 3-year-old girl with blepharophimosis,
      ptosis, and epicanthus inversus syndrome.
AB  - We report on ovarian dysfunction in a 3-year-old girl with blepharophimosis,
      ptosis, and epicanthus inversus syndrome (BPES). A gonadotropin releasing hormone
      test showed hyperresponses of luteinizing hormone (<0.2-->7.2 mIU/ml) and
      follicle-stimulating hormone (7.1-->44.8 mIU/ml), and a human menopause
      gonadotropin test yielded no estradiol response (13-->11 pg/ml). The results
      suggest that primary ovarian failure in type I BPES can take place in early
      childhood.

PMID- 9762010
TI  - Hypothalamic-pituitary-adrenal axis suppression and inhaled corticosteroid
      therapy. 1. General principles.
AB  - The safety of long-term inhaled corticosteroid therapy at commonly prescribed
      doses is an issue of growing concern to physicians and international regulatory
      bodies. This is so because long-term use of these drugs has become the mainstay
      of chronic asthma management and their introduction now is widely recommended in
      official treatment guidelines at the 'mild persistent' stage of asthma, where
      regular daily therapy is first begun. In addition to more frequent use of inhaled
      corticosteroids, there is a further trend to use higher doses of existing inhaler
      therapies and to use the newer and more potent compounds that have recently
      become available. At the same time as these developments have been taking place,
      there has not been a concurrent move to a more rigorous examination of the safety
      profile of these inhaled corticosteroid treatments - especially to assess their
      effects on the hypothalamic-pituitary-adrenal (HPA) axis. Most safety data with
      respect to HPA axis effects have been derived from testing methods that are
      limited in their ability to detect HPA system impairment and, more seriously,
      that can give the impression of functional integrity in the HPA axis when there
      may be moderate (or even greater) impairment. In this first part of a two-part
      review of the HPA axis effects of inhaled corticosteroids and of how these
      effects should be assessed, we examine the currently used and the currently
      available testing methodologies and also review the present state of knowledge
      concerning the structure and function of the HPA axis and the effects of its
      suppression. It is clear that there are state-of-the-art tests to assess in a
      discriminating manner the safety profile of inhaled corticosteroids. These tests
      have been insufficiently employed, including during the drug development process,
      yet they are readily available, relatively inexpensive and can detect adrenal
      suppression before the appearance of clinical effects. In part 2 of this review
      we examine what can be learned about the effects of inhaled corticosteroid
      therapy on the HPA axis from the limited amount of reliable published information
      from clinical and pharmacological studies describing their use and safety.

PMID- 9762011
TI  - Hypothalamic-pituitary-adrenal axis suppression and inhaled corticosteroid
      therapy. 2. Review of the literature.
AB  - In the first part of this two-part review it was noted that inhaled
      corticosteroids had become the mainstay of treatment for chronic asthma and yet
      the effects of long-term use of these compounds on the hypothalamic-adrenal
      pituitary (HPA) axis were largely being determined by testing methods of limited
      reliability, especially by morning plasma cortisol measurements. It was
      established in our examination of the published literature and in our
      presentation of current knowledge of the structure and function of the HPA axis
      that safe, accurate and discriminating techniques to assess the functional status
      of the HPA axis were available. It was concluded that two state-of-the-art tests
      that have been insufficiently used were the ACTH stimulation test and measurement
      of the 24-hour integrated serial plasma cortisol concentrations. These two tests
      can detect adrenal suppression before the appearance of clinical effects. For
      part 2 of this review we conducted an exhaustive search of the English language
      clinical and pharmacological literature on the use of inhaled corticosteroids
      from 1988 until the present time to identify studies in which one or both of
      these testing methods have been used. We present our analysis of this limited
      number of studies to determine what accurately can be known of the HPA axis
      safety profile of three of the most commonly used and investigated inhaled
      corticosteroids - beclomethasone dipropionate, budesonide and fluticasone
      propionate. The first finding of significance was that only 50 reports were
      identified in which information on the HPA axis safety effects of orally inhaled
      steroids in asthma patients or in clinical pharmacological studies met our
      inclusion requirements. By analysis of the data presented in these reports we
      were able to reach the following conclusions: (1) inhaled corticosteroids
      administered chronically, and prudently, within recommended dose ranges do not
      endanger the functioning of the HPA axis, (2) the increasing tendency to use
      higher doses of inhaled corticosteroids on the assumption that there are clear
      dose-response benefits and no adverse HPA axis effects from long-term high-dose
      regimens is misguided and not supported by reliable published information, (3)
      the corollary - that higher corticosteroid potencies (as measured, for example,
      by skin-blanching activity) can have greater therapeutic effect in lung tissue
      without greater concomitant systemic activity - is a flawed concept, and (4) the
      limited clinical and pharmacological data support our part 1 conclusions that
      discriminating techniques to assess the functional HPA axis status should be an
      integral part of the drug development process and that further HPA axis function
      studies are required on existing inhaled corticosteroids - if they lack a
      rigorous testing history or long-term record of clinical safety.

PMID- 9762012
TI  - Cellular signaling mechanisms for stimulation of growth hormone secretion and
      growth hormone primary transcripts by immunosuppressant agents, FK506 and
      cyclosporin A, in cultured rat pituitary cells.
AB  - Although an immunosuppressant, FK506, has been known to stimulate growth hormone
      (GH) release from rat somatotropes, the cellular signaling mechanism is unknown.
      In the present study, intracellular signaling pathways were investigated for
      FK506- and cyclosporin A (CsA)-induced GH release in cultured rat anterior
      pituitary cells. Northern and Western blot analysis revealed that the FK506
      binding protein (FKBP12) and the CsA-binding protein (cyclophilin A) exist at the
      mRNA and protein level in the rat anterior pituitary tissue. FK506 and CsA
      increased GH release in a dose-dependent manner and inhibited calcineurin (CaN)
      activity in the cultured pituitary cells. The third immunosuppressant, rapamycin
      (RP), inhibited the FK506-induced GH release, although RP alone had no effect.
      Protein kinase A (PKA) inhibitors, H-89 and HA-1004 and EGTA blocked FK506- and
      CsA-induced GH release. TGF-beta did not alter basal GH release, but inhibited
      FK506-induced GH release. GH primary transcripts were increased by FK506, and the
      effects were blocked by H-89 and HA-1004. These results suggest that the
      immunosuppressants, FK506 and CsA, stimulate GH release by inhibiting CaN
      activity which results in the activation of the PKA system in the rat
      somatotropes. TGF-beta receptors might be involved in FK506-induced GH release as
      a separate pathway. FK506 also stimulates GH primary transcripts via a PKA
      dependent mechanism in a manner similar to its effects on GH release.

PMID- 9762013
TI  - Effects of a long-term inhalation of fragrances on the stress-induced
      immunosuppression in mice.
AB  - The aim of this study was to determine the effects of the long-term application
      of various fragrances on the suppression of immune response induced by high
      pressure stress in mice. The immune response was analyzed based on plaque-forming
      cell (PFC) count, using mice sensitized with sheep red blood cells. The decreased
      PFC involving thymic involution induced by high-pressure stress in mice was
      restored by exposing the stressed mice to tuberose, lemon, oakmoss and labdanum
      for 24 h following exposure to stress. The decreased PFC and thymic involution
      from stress were restored by exposure to lemon and oakmoss, but not to tuberose
      and labdanum when the mice were exposed to those fragrances continuously for 3
      weeks before the stress was given, followed by exposure to the same fragrances
      for 24 h after the stress. The decreased PFC and thymic involution from stress
      were restored by exposure to lemon and labdanum for 24 h after the stress, but
      not to tuberose over 3 weeks before the stress was given. These data suggest that
      the neuroimmunomodulatory effects of fragrances may be affected by tolerance
      depending on the kinds of fragrances in the case of a long-term application.

PMID- 9762014
TI  - The restraint stress-induced elevation in plasma interleukin-6 negatively
      regulates the plasma TNF-alpha level.
AB  - Although a considerable amount of evidence has shown that physical and
      psychological stress elevates the plasma interleukin 6 (IL-6) levels, the
      physiological significance of such an elevation remains to be elucidated. In this
      study, in order to determine whether the restraint stress-induced elevation of
      plasma IL-6 contributes to the activation of the hypothalamic-pituitary-adrenal
      axis, and whether or not such elevation can affect the inflammatory processes,
      the plasma levels of ACTH, corticosterone, interleukin-1 (IL-1), and tumor
      necrosis factor-alpha (TNF-alpha) in mice pretreated with anti-IL-6 antibody (MP5
      20F3 monoclonal antibody) were compared with those in mice pretreated with rat
      IgG (control antibody) both during and after stress. Both the anti-IL-6-antibody-
      and control-antibody-pretreated mice showed the same extent of plasma ACTH and
      corticosterone increases during stress, and no significant difference was found
      between the two groups of animals. On the other hand, the level of plasma TNF
      alpha in the anti-IL-6-treated animals was also significantly higher than that in
      the control animals both immediately after cessation of stress and 60 min after
      the cessation of the 120-min period of restraint. Plasma IL-1 activity, however,
      did not reach a detectable level in either group of animals at any time point
      examined. These results thus indicate that the restraint-stress-induced elevation
      of plasma IL-6 negatively regulates the plasma TNF-alpha levels and may thus
      contribute to the maintenance of homeostasis.

PMID- 9762015
TI  - Repeated in vivo hydrocortisone treatment promotes a dual modulation of
      cytokeratin expression by mouse thymic epithelial cells.
AB  - Previous studies showed that a single dose of hydrocortisone in mice was able to
      transiently upregulate the expression of cytokeratins (CKs) 3 and 10 by medullary
      epithelial cells of the mouse thymus. Herein we studied these cells (specifically
      recognized by immunocytochemistry with the anti-CK monoclonal antibody KL1)
      following a series of repeated injections of the glucocorticoid hormone. A
      progressive dual (up and down) modulation of KL1+ medullary epithelial cells was
      observed with a late appearance of KL1 immunoreactivity in the thymic cortex. The
      data indicate that a single versus repeated exposure to high doses of
      glucocorticoid hormone may trigger different circuits regulating intrathymic CK
      expression. Lastly, the model described herein may be regarded as promising in
      studies concerning the effect of repeated stress conditions upon the thymus.

PMID- 9762016
TI  - Nicotine for pyoderma gangrenosum.

PMID- 9762017
TI  - Evaluation of clinical criteria for diagnosis of bullous pemphigoid. French
      Bullous Study Group.
AB  - OBJECTIVE: To check the potential usefulness of clinical criteria for the
      diagnosis of bullous pemphigoid when state-of-the-art techniques such as Western
      immunoblotting, immunoprecipitation, and indirect immunofluorescence on salt
      split skin or direct immunoelectron microscopy are not available. DESIGN:
      Comparison of the clinical criteria between 2 groups (with and without bullous
      pemphigoid) as defined by immunoelectron microscopy used as standard criterion,
      in a prospective study. Multivariate logistic regression analysis was carried out
      by including all items that were statistically significant (at P < .05 level) in
      univariate analysis. SETTING: Five dermatology departments in teaching hospitals.
      PATIENTS: The 231 patients studied had subepidermal autoimmune bullous diseases
      with linear IgG or C3 deposits in the basement membrane zone (157 with bullous
      pemphigoid, 33 with cicatricial pemphigoid, 30 with epidermolysis bullous
      acquisita, 5 with lupus erythematosus, and 6 others). A second set of patients
      was used to calculate predictive values. RESULTS: The multivariate logistic
      stepwise analysis resulted in a final set of predictors that included only 4
      items: absence of atrophic scars, absence of head and neck involvement, absence
      of mucosal involvement, and age greater than 70 years. No additional variables
      met the .05 significance level to enter into the model. If 3 of these 4
      characteristics were present, a diagnosis of bullous pemphigoid could be made
      with a sensitivity of 90% and a specificity of 83%; these predictive values were
      calculated on a sample of 70 new cases. CONCLUSIONS: With and estimated incidence
      of bullous pemphigoid among subepidermal autoimmune bullous diseases of 80%, the
      presence of 3 of the 4 significant criteria allows the diagnosis of bullous
      pemphigoid, with a positive predictive value of 95%. Our set of clinical criteria
      thus allows the diagnosis of bullous pemphigoid with good validity for both
      clinical practice and therapeutic trials.

PMID- 9762018
TI  - Disease associations in polymorphous light eruption. A long-term follow-up study
      of 94 patients.
AB  - OBJECTIVES: To examine the long-term outcome of polymorphous light eruption (PLE)
      in a large patient population and to evaluate associated conditions, especially
      lupus erythematosus, during the course of the disease. DESIGN: A questionnaire
      based follow-up study an average of 32 years after onset of PLE. The study was
      complemented by clinical examination of the patients with PLE similarly studied
      16 years earlier or now reporting equal or worse PLE symptoms compared with the
      1978-1979 follow-up or any symptoms suggesting an autoimmune disease. SETTING: A
      dermatologic clinic in a university hospital. PATIENTS: Ninety-four of the
      original cohort of 138 patients with PLE (87% of living patients) returned the
      questionnaire, and 46 (84%) of the 55 patients invited volunteered for clinical
      examination. INTERVENTION: None. MAIN OUTCOME MEASURES: Clinical characteristics
      of PLE and clinical laboratory findings referring to associated diseases,
      especially lupus erythematosus. RESULTS: Twenty-three (24%; 95% confidence
      interval [CI], 16%-34%) of the 94 patients were cured, 48 (51%; 95% CI, 41%-62%)
      experienced milder symptoms, and 23 (24%; 95% CI, 16%-34%) experienced equal or
      worse symptoms than in the 1978-1979 follow-up. At least 1 autoimmune disease was
      diagnosed at some point in 14 patients (15%; 95% CI, 12%-29%) (in 13 [18%] of the
      female patients) and lupus erythematosus specifically in 2 (2%; 95% CI, 0%-7%)
      (in 2 [3] of the female patients). The prevalence of a thyroid disease was 14%
      (13 patients) (95% CI, 8%-23%). CONCLUSION: Polymorphous light eruption is a long
      standing slowly ameliorating disease with some tendency to development of
      autoimmune disease or thyroid disorder, especially in female patients, but the
      risk for lupus erythematosus is not increased.

PMID- 9762019
TI  - Managed care and the treatment of skin disease, 1995. Continued growth and
      emerging dominance.
AB  - OBJECTIVE: To document changes in type of financing for office-based visits for
      the treatment of common skin conditions and to dermatologists. DESIGN: Data from
      a national survey of visits to office-based practitioners conducted by the
      National Center for Health Statistics were used. The stratified sampling
      technique permits estimation of the total number of office visits with specific
      characteristics in the United States. SETTING: A national probability sample of
      visits to office-based practitioners occurring in 1995. SUBJECTS: In 1995, 36,875
      visits were sampled. Of these, 2121 were for common skin problems to any
      physician and 1886 were visits for any reason to dermatologists. MAIN OUTCOME
      MEASURES: The distribution source of payment and presence of managed care
      arrangements for office visits for common skin problems and to dermatologists.
      INTERVENTION: None. RESULTS: In 1995, preferred provider and health maintenance
      organizations provided payment for 34% of all ambulatory care and 38% of office
      visits for common skin complaints. CONCLUSION: Managed care is already the
      dominant mechanism of payment for the treatment of skin disease for many patient
      groups and in many areas of the country. Preferred provider organizations are
      much more likely to employ dermatologists to provide care of common skin problems
      than are health maintenance organizations. If the recent trends continue, by year
      2000 most patients seen by dermatologists will be seen under the auspices of
      managed care systems.

PMID- 9762021
TI  - Topical tacrolimus is not effective in chronic plaque psoriasis. A pilot study.
AB  - BACKGROUND: Cyclosporine for the treatment of psoriasis constitutes a new
      approach. Alternative systemic cyclosporine derivatives have been studied to find
      an immunosuppressive drug with fewer adverse effects. Tacrolimus is one of these
      new immunosuppressive drugs. Systematically, it has been proven effective in
      treating psoriasis. A topical formulation of tacrolimus is attractive because it
      has fewer adverse effects and is useful for a large group of patients. We report
      for the first time on the efficacy of nonocclusive topical tacrolimus in the
      treatment of psoriasis. OBSERVATIONS: After a washout phase of 2 weeks, patients
      were randomized to receive 0.005% calcipotriol ointment twice daily, placebo
      ointment once daily, or 0.3% tacrolimus ointment once daily. One psoriatic plaque
      was treated with a surface area of 40 to 200 cm2. Efficacy was estimated using
      the local psoriasis severity index. The reduction in the local psoriasis severity
      index score after 6 weeks was 62.5% in the calcipotriol group, 33.3% in the
      tacrolimus group, and 42.9% in the placebo group. CONCLUSIONS: There was no
      statistically significant difference between the efficacy of tacrolimus and
      placebo ointment (P = .77). Calcipotriol ointment, applied twice daily, had a
      better effect than tacrolimus ointment and placebo ointment once daily.

PMID- 9762020
TI  - Reports by patients and dermatologists of skin cancer preventive services
      provided in dermatology offices.
AB  - OBJECTIVE: To learn how often patients receive skin cancer preventive services in
      dermatologists' offices. DESIGN: Survey of dermatology patients and
      dermatologists. SETTING: Dermatology practices of full-and part-time faculty at a
      midwestern medical school. PARTICIPANTS: Patients were randomly selected from
      clinical sessions of 11 dermatologists. Of 200 patients enrolled, 162 (81%)
      responded to the survey. Ten (91%) of the dermatologists responded, and 4
      additional dermatologists from the faculty were also surveyed. MAIN OUTCOME
      MEASURES: Patients' and dermatologists' reports of the provision of skin cancer
      prevention counseling and screening for skin cancer. RESULTS: Most patients (93%)
      had been informed about the risks of sun exposure, but for only 27% was a
      dermatologist the main source of information. Although 76% of patients had seen a
      dermatologist at least twice in the last 5 years, only 34% reported that they had
      ever received a total-body screening examination for skin cancer. Most patients
      (55%) would like to learn more about skin cancer prevention, and responded that
      they would learn best from a brochure (43%) or from a dermatologist (42%). All
      dermatologists believed that some skin cancer preventive services should be
      provided to each patient, but they varied widely in the proportion of their white
      adult patients to whom they provided such services. For example, with respect to
      counseling about sunscreens, the same number of dermatologists (4 [29%])
      responded that they counsel 25% or less of their patients, and more than 75% of
      their patients. CONCLUSION: There is wide variation in how often skin cancer
      preventive services are provided in dermatologists' offices.

PMID- 9762022
TI  - Treatment of pemphigus with gold.
AB  - BACKGROUND: Although gold has been reported to be useful in treating pemphigus
      vulgaris, its use has waned in recent years because of concerns regarding
      efficacy and toxicity. OBJECTIVE: To review 26 patients with pemphigus who were
      treated with intramuscular gold over a 10-year period. RESULTS: Gold was
      effective in 62% of patients as a primary treatment for pemphigus or as a steroid
      sparing agent. An average of 3 months of therapy was required before the daily
      prednisone dosage could be halved. Four patients were free of disease and stopped
      receiving all therapy at the conclusion of the study. Toxic effects due to gold
      therapy developed in 42% of patients and all adverse effects resolved with its
      cessation. CONCLUSIONS: While toxic effects limit the use of gold in many
      patients with pemphigus, it may be effective in treating a large percentage of
      patients who otherwise are unable to reduce their steroid requirement. Because of
      its delayed onset of action, patients treated with gold usually require systemic
      steroids when therapy is initiated. Controlled, prospective trials are needed to
      further evaluate the efficacy of gold and its potential steroid-sparing effects.

PMID- 9762023
TI  - Human herpesvirus 6 infection as a risk factor for the development of severe drug
      induced hypersensitivity syndrome.
AB  - BACKGROUND: Drug-induced hypersensitivity syndrome is characterized by a severe,
      potentially fatal, multiorgan hypersensitivity reaction that usually appears
      after prolonged exposure to certain drugs. Its delayed onset and clinical
      resemblance to infectious mononucleosis suggest that underlying viral infections
      may trigger and activate the disease in susceptible individuals receiving these
      drugs. OBSERVATIONS: A 60-year-old woman developed an itchy, generalized,
      erythematous, confluent rash on the 39th day of receiving allopurinol therapy.
      Even after she discontinued treatment with allopurinol, her skin lesions
      progressed to severe blistering skin eruption. After the patient started oral
      prednisone therapy, her skin lesions resolved with desquamation. After complete
      resolution, rechallenge with allopurinol led to the development of an
      erythematous eruption. Titers of human herpesvirus 6 IgG antibodies dramatically
      increased with the development of the eruption. The results of a polymerase chain
      reaction and in situ hybridization indicated the presence of human herpesvirus 6
      in the skin lesions, although human herpesvirus 7 DNA was detected only by in
      situ hybridization. CONCLUSION: Reactivation of human herpesvirus 6, possibly in
      concert with human herpesvirus 7, can contribute to the development of a severe
      drug-induced hypersensitivity syndrome.

PMID- 9762024
TI  - Severe hypersensitivity syndrome due to sulfasalazine associated with
      reactivation of human herpesvirus 6.
AB  - BACKGROUND: A severe adverse reaction to sulfasalazine therapy has been
      associated with hypersensitivity syndrome, the clinical features of which are
      similar to infectious mononucleosis. No serologic evidence of viral infections
      has been reported with this syndrome; however, human herpesvirus 6 infection has
      not been specifically investigated, which could cause an infectious
      mononucleosislike syndrome. OBSERVATIONS: We report 2 cases of hypersensitivity
      syndrome induced by the use of sulfasalazine. The clinical features of the
      syndrome appeared 18 and 32 days after administration of sulfasalazine. Clinical
      signs included a maculopapular rash progressing to exfoliate erythroderma, fever,
      and lymphadenopathy. Leukocytosis, atypical lymphocytes, liver dysfunction, and
      renal disturbance were also observed. In 1 patient, human herpesvirus 6 variant B
      was isolated from peripheral blood mononuclear cells, and in both patients anti
      human herpesvirus 6 IgG titers increased considerably. CONCLUSIONS: Two cases of
      hypersensitivity syndrome due to sulfasalazine use were associated with the
      reactivation of human herpesvirus 6, which may be a required cause of
      hypersensitivity syndrome.

PMID- 9762025
TI  - Infantile pyramidal protrusion as a manifestation of lichen sclerosus et
      atrophicus.
AB  - BACKGROUND: A perineal infantile lesion previously described as "skin tag/fold"
      had recently been named infantile perianal pyramidal protrusion. It appears on
      the perineal median raphe of girls as a pyramidal soft tissue swelling, covered
      by smooth, red or rose-colored skin. Its pathogenesis is unknown. As in the case
      of other perianal lesions, knowledge about it is important, as concern about
      signs of child abuse grows. OBSERVATIONS: Four girls, 2 of them sisters, with
      infantile perianal pyramidal protrusion were studied. Three of these girls showed
      subtle clinical evidence of classic lichen sclerosus et atrophicus on first
      examination. The other girl developed vulvar lesions of lichen sclerosus et
      atrophicus months after the diagnosis of infantile perianal pyramidal protrusion.
      All 4 protrusions disclosed histopathological findings diagnostic of lichen
      sclerosus et atrophicus. CONCLUSIONS: Infantile perianal pyramidal protrusion is,
      at least in some patients, a peculiar form of lichen sclerosus et atrophicus that
      can precede other, more characteristic manifestations. We suggest changing the
      name to the more precise infantile perineal protrusion. Knowledge of this
      hitherto unrecognized clinical form of lichen sclerosus et atrophicus can help to
      explain anogenital symptoms and avoid its misinterpretation as a sign of sexual
      abuse.

PMID- 9762026
TI  - Congenital cutaneous defects as complications in surviving co-twins. Aplasia
      cutis congenita and neonatal volkmann ischemic contracture of the forearm.
AB  - BACKGROUND: During twin pregnancies, several complications may result in the
      death of a co-twin depending on the date of death. We describe herein 2 infant
      survivors of monozygotic twin pairs with 2 distinct possible complications: a
      aplasia cutis congenita and Volkmann ischemic contracture. OBSERVATIONS: One
      infant had extensive aplasia cutis congenita with an associated monozygotic co
      twin who died at 3 months of gestation, and the other child had a localized arm
      defect due to Volkmann ischemic contracture and brain damage, with a co-twin who
      died at approximately 6 weeks of gestation. CONCLUSIONS: Congenital cutaneous
      defects may result in the death of a co-twin. The most common of these defects is
      aplasia cutis congenita associated with a fetus papyraceus or a dead fetus
      related to ischemic/thrombotic events in the placenta and fetus. Volkmann
      ischemic contracture is rare in the newborn but can cause neonatal cutaneous
      defects. The cause of Volkmann ischemic contracture in newborns is unknown;
      however, our second observation suggests the possible role of a dead fetus.

PMID- 9762027
TI  - Waldenstrom macroglobulinemia-induced bullous dermatosis.
AB  - BACKGROUND: Waldenstrom macroglobulinemia is a plasma cell dyscrasia of
      undetermined cause characterized by the monoclonal proliferation of
      lymphoplasmacytes in the bone marrow, lymph nodes, and spleen and elevated
      circulating levels and tissue deposition of monoclonal IgM produced by these
      aberrant cells. Rarely, cutaneous manifestations of this disease have been
      reported. OBSERVATIONS: We report the case of a patient with bullous dermatosis
      induced by Waldenstrom macroglobulinemia and demonstrate the subepidermal
      location of the separation and the presence of IgM and kappa light chains by
      immunoperoxidase, immunofluorescent techniques, and electron microscopy with
      immunogold staining. Immunoblotting revealed a strong band at the 290-kd area.
      CONCLUSIONS: The demonstration of the separation in the upper dermis at the site
      of IgM deposits suggests that these deposits may be an etiologic factor in this
      rare manifestation.

PMID- 9762028
TI  - Bullous pemphigoid. The latest in diagnosis, prognosis, and therapy.

PMID- 9762029
TI  - Chronic plaques in a patient with ataxia telangiectasia. Cutaneous granulomatous
      lesions in a patient with AT.

PMID- 9762030
TI  - Tumor of the right shoulder in a newborn. Bossed hemangioma with telangiectasia
      and peripheral pallor.

PMID- 9762031
TI  - Skin ulcers associated with a tender and swollen arm. Pyoderma gangrenosum (PG)
      in association with chronic recurrent multifocal osteomyelitis (CRMO).

PMID- 9762032
TI  - Perianal dermatitis in a child. Perianal streptococcal dermatitis (PSD).

PMID- 9762034
TI  - Human herpesviruses 6 and 7. New roles yet to be discovered?

PMID- 9762033
TI  - Do we have time for the change?

PMID- 9762035
TI  - Mergers, separations, and transformations of dermatology residency training
      programs: a resident's perspective.

PMID- 9762036
TI  - Don't dispense with dispensing.

PMID- 9762037
TI  - Who should care for hospitalized patients with severe skin disease?

PMID- 9762038
TI  - The proper future for medical dermatology.

PMID- 9762039
TI  - Declining interest in medical dermatology.

PMID- 9762040
TI  - No evidence of HHV-8 infection in patients with pemphigus vulgaris/foliaceus.

PMID- 9762041
TI  - Adverse effects of spironolactone therapy in women with acne.

PMID- 9762042
TI  - Anaphylaxis to intradermal triamcinolone acetonide.

PMID- 9762043
TI  - Alopecia areata has low plasma levels of the vasodilator/immunomodulator
      calcitonin gene-related peptide.

PMID- 9762044
TI  - Helicobacter pylori eradication in patients with chronic urticaria.

PMID- 9762045
TI  - Nail bed dyschromia secondary to docetaxel therapy.

PMID- 9762046
TI  - Unilateral abdominal distention following herpes zoster outbreak.

PMID- 9762047
TI  - Treatment of acyclovir-resistant, foscarnet-unresponsive HSV infection with
      topical cidofovir in a child with AIDS.

PMID- 9762048
TI  - Genetic analysis of a trichoepithelioma and associated basal cell carcinoma.

PMID- 9762049
TI  - [Vena cava umbrella filter: complications and treatment].
AB  - BACKGROUND AND OBJECTIVE: Increasing numbers of vena canal filters are being
      implanted to prevent pulmonary embolism, which are mainly the consequence of deep
      vein and pelvic vein thrombosis. Can a filter be removed again in case of
      complications arising from it? What is the risk of such operative explantation?
      What is the subsequent risk of pulmonary embolism? PATIENTS AND METHODS: In nine
      patients (5 males, 4 females; mean age 45 (30-39 years) who had vena caval
      filters implanted because of thromboembolism despite anticoagulation,
      complications due to the filter required its operative removal and thrombectomy
      of the large veins 3 days to 48 months after implantation in the inferior vena
      cava (IVC). One inguinal arteriovenous fistula (due to perforation of rods of a
      displaced filter) were closed. The patients' case note were retrospectively
      analysed and eight of the nine patients' were reexamined according to a
      standardized procedure a mean of 20 months after removal of the filter. RESULTS:
      Explantation of the filter had been successful in all patients. But there were
      two nonfatal postoperative complications: a pulmonary embolus and a paradoxical
      cerebral embolus. In one patient a segmental stenosis of the IVC with
      retroperitoneal collateral circulation was found at operation. All but one of 16
      pelvic veins that had thrombectomies performed at the time of filter explanation
      were patent, as were the IVCs in seven of the eight re-examined patients. None of
      the patients had evidence of postoperative pulmonary embolism. CONCLUSIONS: Vena
      caval filters can be explanted with a low operative risk. After removal and
      venous thrombectomy, implantation of another caval filter is unnecessary. As
      anticoagulation properly monitored is almost always an effective measure in the
      prevention of pulmonary thromboembolism, filter implantation should be performed
      only on the strictest indication, as an ultimate step.

PMID- 9762050
TI  - [Anal gland carcinoma with osteoblastic metastases].
AB  - HISTORY AND CLINICALLY FINDINGS: A 52-year-old woman was admitted because of anal
      pain of 6 weeks duration. Physical examination was unremarkable except for a
      cherry-sized swelling, painful to pressure, on rectal examination. As the
      erythrocyte sedimentation rate and C-reactive protein were increased (69/115 and
      12.1 mg/dl, respectively) and abscess was diagnosed. Carcinoembryonic antigen was
      within normal limits. INVESTIGATIONS: At rectoscopy a fluctuating abscess-linked
      swelling was found at 3 cm and a submucous tumour at 5 cm from the anus.
      TREATMENT AND COURSE: The abscess was cut open and at the level of the dentate
      line a submucous adenocarcinoma about 3 cm in diameter was resected. A small
      residual tumour was removed by abdomino-perineal rectal extirpation. As
      histologically it was an adenocarcinoma not of colorectal type, without
      relationship to rectal mucosa but in close contact to the anal glands, and the
      further course did not indicate a metastasis from another primary tumour, the
      diagnosis of anal gland adenocarcinoma was established. A local recurrency was
      resected 6 months later, followed by combined radio- and chemotherapy. A diffuse
      osteoblastic metastasis was discovered later and the patient died 21 months after
      diagnosis. CONCLUSION: An osteoblastic metastasis from an anal gland carcinoma,
      as occurred in this case, has not been previously reported.

PMID- 9762051
TI  - [Primary varices of the colon. A rare cause of gastrointestinal bleeding].
AB  - HISTORY: A 34-year-old patient presented with a two-day history of passing bright
      red blood with his stools. There was no contributory past or family history and
      he had no accompanying symptoms. INVESTIGATIONS: Colonoscopy revealed many
      varices in the colon and terminal ileum without an active source of bleeding.
      Angiography failed to demonstrate any bleeding or vascular anomaly in the
      splanchnic region. Abdominal ultrasound and gastroscopy as well as biochemical
      tests did not indicate portal hypertension or liver cirrhosis. TREATMENT AND
      COURSE: On the night of admission there was a renewed fall in haemoglobin
      concentration. Emergency colonoscopy again failed to discover a source of
      bleeding. After transfusion of four units of erythrocyte concentrate the further
      course was uneventful. 8 months and 3 years later there were further episodes of
      marked bleeding per rectum. At the latest admission no source for the bleeding
      was found but there was some blood oozing in the sigmoid colon. Biochemical tests
      were unremarkable. The large varices were again seen in the colon and terminal
      ileum. Gastroscopy, Doppler sonography of the liver and repeat abdominal
      sonography again failed to demonstrate portal vein thrombosis, liver cirrhosis or
      portal hypertension. CONCLUSION: In case of colonic varices the differential
      diagnosis should include portal hypertension with chronic liver disease, portal
      vein thrombosis, vascular anomalies or postoperative complications. The treatment
      of primary varices, which are rare, is conservative.

PMID- 9762052
TI  - [Diagnosis of extracranial carotid stenosis].

PMID- 9762053
TI  - [Left heart assist device or heart transplantation? New strategies for the
      treatment of terminal heart insufficiency].

PMID- 9762054
TI  - [Danger for exposure of waste collection and removal workers to infectious
      agents].

PMID- 9762055
TI  - Oral anticoagulants.

PMID- 9762056
TI  - Attention deficit hyperactivity disorder: focus on genetics.

PMID- 9762057
TI  - Restructuring hospital services.

PMID- 9762058
TI  - Peer review on the Internet: launching eMJA peer review study 2.

PMID- 9762059
TI  - Paediatric rotavirus gastroenteritis: where to now in prevention and treatment?

PMID- 9762060
TI  - Effectiveness of anticoagulation among patients discharged from hospital on
      warfarin. The Newcastle Anticoagulation Study Group.
AB  - OBJECTIVES: To examine the effectiveness of anticoagulation among patients
      discharged from hospital on warfarin in the care of general practitioners (GPs).
      DESIGN AND SETTING: A historical cohort with questionnaires to patients
      discharged from a major metropolitan teaching hospital and their GPs.
      PARTICIPANTS: Patients discharged between 1 February 1995 and 31 January 1996
      identified from hospital pharmacy records as being prescribed warfarin, and their
      treating GPs. MAIN OUTCOME MEASURES: Frequency of testing and levels of
      international normalised ratio of prothrombin time (INR) within six months of
      discharge; level of INR aimed at by GP; complication rates; and patient knowledge
      about anticoagulation. RESULTS: Replies were received from 242 (68%) patients and
      pathology records were examined for 195 (81%) of these. The median gap between
      INR measures was seven days. The median of the median INR level for each patient
      was 2.4 (rising to 2.7 in patients with an artificial heart valve); 24% of
      observed patient time was spent at an INR level of less than 2.0, 54% between 2.0
      and 2.9, 18% between 3.0 and 3.9 and 4% at an INR level of 4.0 or more. There
      were five confirmed major complications (equivalent to 5 per 100 patient-years).
      Twenty-seven per cent of patients answered at least eight of the 10 knowledge
      questions correctly: education level predicted knowledge, but there was no
      relationship between knowledge and INR level. CONCLUSIONS: Among this unselected
      group of patients whose anticoagulation was managed by GPs, there was a high
      frequency of laboratory testing. INR levels were controlled safely and
      complication rates were comparable with those in published reports.

PMID- 9762061
TI  - Re-engineering the elective surgical service of a tertiary hospital: a historical
      controlled trial.
AB  - OBJECTIVE: To study the clinical effects of re-engineering the processes
      associated with elective surgery. DESIGN: A prospective, historical controlled
      trial. Control patients were enrolled from March 1995 to January 1996, and
      postintervention patients from February 1996 to October 1996. SETTING: A major
      teaching, tertiary care hospital (Prince of Wales Hospital, Sydney). PATIENTS:
      224 patients (123 before and 101 after the intervention) undergoing elective
      herniorrhaphy of laparoscopic cholecystectomy who lived in the local area.
      INTERVENTION: Introduction of a re-engineered surgical service consisting of
      preadmission assessment and education, admission on day of surgery, and postacute
      care after discharge. There were no changes to the operative methods or infection
      control procedures. MAIN OUTCOME MEASURES: Length of stay, operative
      complications, pain scores and patient satisfaction. RESULTS: The risk of a
      patient suffering one or more complications was reduced in the postintervention
      group (postintervention v. control patients: 25.7% v. 38.2%; relative risk [RR],
      0.66; 95% confidence interval [CI], 0.44-0.98; P = 0.035) because of a reduced
      risk of wound infections (5.0% v. 16.3%; RR, 0.30; 95% CI, 0.12-0.78; P =
      0.0075). Other complications (perioperative or postoperative) and pain scores
      were unchanged. Patients treated by the re-engineered service had a significantly
      shorter length of stay, reported a higher level of satisfaction with the
      preoperative and postdischarge care, and were more likely to say that they would
      have the same treatment again (92.9% v 82.6%; P = 0.037). CONCLUSIONS: Re
      engineering surgical services, with an associated reduction in length of stay,
      does not lead to a deterioration in care and may decrease postoperative
      complications and increase patient satisfaction.

PMID- 9762062
TI  - Rotavirus infection and rates of hospitalisation for acute gastroenteritis in
      young children in Australia, 1993-1996.
AB  - OBJECTIVE: To determine rates of hospitalisation of young children for acute
      gastroenteritis in Australia, and to estimate the proportion of these admissions
      caused by rotavirus infection. DESIGN: Analysis of hospital admission records,
      and parallel, prospectively collected data on rotavirus-positive admissions.
      SETTING: Hospitals admitting young children in all Australian States and
      Territories in 1993-1996. PATIENTS: All children under five years admitted to
      hospital for acute gastroenteritis (International Classification of Diseases,
      ninth revision principal diagnosis codes 003.0, 004.0-009.3 and 558.9). MAIN
      OUTCOME MEASURES: Rate of hospital admission per 1000 children per year by State,
      and the proportion of admissions caused by rotavirus infection. RESULTS: There
      were almost 20,000 hospital admissions annually in Australia for acute
      gastroenteritis in children under five years, at an average rate of 15/1000. An
      estimated 50% of these were attributable to rotavirus infection, implying a rate
      of hospitalisation for rotavirus-related gastroenteritis of 7.5/1000/year. Among
      children under two years this rate was 11.6/1000. Rotavirus incidence rates
      generally followed a typical seasonal pattern in temperate regions of the
      country, with sharp peaks in mid to late winter. Rates of hospitalisation varied
      markedly, even between States with apparently similar patterns of disease, while
      the incidence in the Northern Territory was 3-5 times higher than other States.
      CONCLUSIONS: Rotavirus-related gastroenteritis is a major cause of hospital
      admissions in young children, and large savings to the healthcare system are
      possible if it can be prevented at reasonable cost. Variation in treatment
      practices between States may be worth studying in greater detail as another
      source of potential savings.

PMID- 9762063
TI  - A life-threatening anaphylactoid reaction to polyvalent snake antivenom despite
      pretreatment.
AB  - A 44-year-old man suffered a life-threatening anaphylactoid reaction to
      polyvalent snake antivenom, although he had been given the recommended
      pretreatment. Further research is needed to determine if pretreatment is
      necessary.

PMID- 9762065
TI  - "Pharmaceutical security": a new research agenda?

PMID- 9762064
TI  - Systematic review of Propionibacterium acnes resistance to systemic antibiotics.
AB  - OBJECTIVE: To document changes in the prevalence of resistance of
      Propionibacterium acnes to antibiotics used for treating acne. DATA SOURCES:
      MEDLINE and EMBASE were searched for publications on P. acnes resistance to
      systemic antibiotics. The search strategy mapped "acne" or "acne vulgaris" with
      the terms "antibiotic resistance" or "drug resistance, microbial". Only papers
      published in English during 1976 to 1997 were included in the search. STUDY
      SELECTION: 53 publications met the search criteria. The search output was refined
      by selecting papers that specifically addressed P. acnes resistance patterns.
      Additional studies (not included in the search output) were identified from
      review articles and references of the retrieved articles. Twelve articles were
      reviewed. DATA EXTRACTION: Data on the prevalence of antibiotic-resistant
      propionibacteria, the incidence of individual resistance phenotypes, mixed
      resistance, and correlation between poor therapeutic response and resistant
      propionibacteria were extracted. DATA SYNTHESIS: Research since 1978 has
      suggested an association between poor therapeutic response and antibiotic
      resistant propionibacteria. The overall incidence of P. acnes antibiotic
      resistance has increased from 20% in 1978 to 62% in 1996. Resistance to specific
      antibiotics varied and was most commonly reported with erythromycin and
      clindamycin, tetracycline and doxcycline, and trimethoprim. Resistance to
      minocycline is rare. CONCLUSIONS: In many patients with acne, continued treatment
      with antibiotics can be inappropriate or ineffective. It is important to
      recognise therapeutic failure and alter treatment accordingly. The use of long
      term rotational antibiotics is outdated and will only exacerbate antibiotic
      resistance.

PMID- 9762066
TI  - Magnetic resonance cholangiopancreatography: non-invasive imaging for the biliary
      tree and pancreatic duct.
AB  - Producing images similar to those acquired by the invasive procedures of
      endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous
      transhepatic cholangiography, magnetic resonance cholangiopancreatography (MRCP)
      is indicated in patients who are unable to undergo ERCP or have had previously
      unsuccessful ERCP. It is used increasingly in non-invasive evaluation of the
      pancreaticobiliary tree in cases where the need for intervention during ERCP is
      expected to be low. MRCP may help in identifying anomalous biliary anatomy or
      choledocholithiasis before laparoscopic cholecystectomy, and in deciding between
      percutaneous or endoscopic treatment for patients with obstructive jaundice to
      decrease the rate of failed ERCP procedures.

PMID- 9762067
TI  - Premature closure of the fetal ductus arteriosus after maternal use of non
      steroidal anti-inflammatory drugs. Adverse Drug Reactions Advisory Committee.

PMID- 9762068
TI  - Irritable bowel syndrome.

PMID- 9762069
TI  - Hazards of hot water use for plaster of Paris slabs.

PMID- 9762070
TI  - Should there be an accredited ethics committee system for centralised review of
      multicentre clinical research?

PMID- 9762071
TI  - Should there be an accredited ethics committee system for centralised review of
      multicentre clinical research?

PMID- 9762072
TI  - Should there be an accredited ethics committee system for centralised review of
      multicentre clinical research?

PMID- 9762073
TI  - Should there be an accredited ethics committee system for centralised review of
      multicentre clinical research?

PMID- 9762074
TI  - Prescription use by patients with concession cards.

PMID- 9762075
TI  - General internal medicine in Australia and New Zealand--a renaissance.

PMID- 9762076
TI  - Infant pertussis deaths in New South Wales 1996-1997.

PMID- 9762077
TI  - Sporotrichosis in a Queensland bushwalker.

PMID- 9762078
TI  - "Fisting" as a cause of vaginal bleeding.

PMID- 9762080
TI  - Circular dichroic analysis of protein conformation: inclusion of the beta-turns.
AB  - The mean residue ellipticity, [theta], at any wavelength, lambda, of a protein in
      aqueous solution is expressed as [theta]lambda = fH[theta]H infinity(1-k/n) + f
      beta[theta]beta + ft[theta]t + fR[theta]R with two constraints: 1 > or = fj > or
      = 0 and sigma fj = 1. The subscripts H, beta, t, and R refer to the helix, beta
      form, beta-turn, and unordered form. The fractions, fj's, of 15 proteins are
      based on X-ray crystallography, ft refers to the net beta-turn after cancelling
      those residues having dihedral angles of opposite sign. The [theta]H infinity of
      an infinite helix and its chain-length dependence factor, k, were computed from
      the myoglobin data (Chen et al., 1974, Biochemistry 13, 3350). The average number
      of residues per helical segment, n, for 15 proteins was about 10, which can be
      used for proteins of unknown structure. The reference spectra of other three
      structural elements are computed by a least-squares method. Once the reference
      spectra are chosen, the same equation above can be used to estimate the fractions
      of the secondary structure of a protein from its CD data points between 190 and
      240 nm at 1-nm intervals. The computed helical content is usually good to
      excellent (concanavalin A is a notable exception). Inclusion of the beta-turn in
      the analysis improves the correlation for the estimates of the beta-form, but the
      computed beta t values are not significantly correlated with the X-ray results.
      Matrix formulation proves the equivalence of the least-squares method and the
      integral curve-fitting.

PMID- 9762079
TI  - Preparative gel electrophoresis: detection, excision, and elution of protein
      bands from unstained gels.
AB  - Methods are described for localizing proteins in unstained gels and accurately
      excising the regions containing them. A gel elutor, which is all glass with
      Lucite fittings, is also described. The elutor removes proteins from gels with a
      high yield and concentrates the protein in a small volume. The elutor is simple
      and very easy to use. A way is presented for avoiding the oxidation of methionine
      and cysteine during preparative electrophoresis.

PMID- 9762081
TI  - A new method to characterize saturation functions by their first four moments.
AB  - The calculation of the first four moments of saturation functions is proposed as
      a method to describe the properties of enzymes or receptors models. The values of
      these moments in the case of the Langmuir or Michaelis-Menten equation and the
      Hill equation are reviewed. They have been calculated for the second degree Adair
      equation and in the case of binding site heterogeneity. A method for
      generalization to cases of greater complexity is also proposed. The advantage of
      this method over the classical ones--graphical representations and derivation of
      coefficients like nH, [L]0.9/[L]0.1 ...--is essentially that the moments are
      defined by one single value independently of any particular model for the whole
      of the saturation curve.

PMID- 9762082
TI  - Improved radioisotopic assay for cytidine 5'-triphosphate synthetase (EC
      6.3.4.2).
AB  - An improved radioassay for cytidine 5-triphosphate synthetase is reported which
      employs thin-layer chromatographic methods and provides a number of advantages
      over previously available techniques. (i) The method resolves the nucleotides and
      the degradation products generated during the time course of the enzymatic
      reaction by ascending chromatography employing polyethyleneimine cellulose
      plastic-backed sheets. (ii) Determinations of CTP formed and all nucleotide pairs
      generated during kinetic analysis of CTP synthetase are greatly simplified,
      further facilitating the detection of extraneous enzymatic activities. (iii) The
      sensitivity of the assay is enhanced and as little as 50 pmol of product formed
      was readily detected in supernatant fluids. This was made possible, in part, by
      the addition of NaF and phosphoenolpyruvate which together maintain the
      nucleotide triphosphates in the reaction mixture. (iv) A large number of samples
      can be handled at one time with highly reproducible results. The synthesis of CTP
      from UTP by enzyme preparations from rat liver, hepatomas, and Salmonella
      typhimurium LT2 was quantitated with this method.

PMID- 9762083
TI  - A simple technique for the measurement of unidirectional calcium influx at the
      mucosal surface of organ-cultured embryonic chick duodenum.
AB  - Unidirectional calcium influx can be measured by application of a filter paper
      blotter saturated with a 45Ca-labeled buffer solution to the mucosal surfaces of
      slit-open embryonic chick duodena which had been cultured mucosal side up on
      stainless-steel grids. The results obtained with this simple technique support
      the contention of a direct involvement of a vitamin D-induced calcium-binding
      protein in the transport of calcium across the mucosal surface. Permeability and
      inulin space measurements validate the method for measurement of calcium influx
      at initial velocity and obviate concern for "unstirred layer" effects. Kinetic
      analyses indicate a two step influx process, one saturable at about 5 mM calcium
      and the other essentially unsaturable.

PMID- 9762084
TI  - A quick hydroxyapatite chromatography technique especially adapted for work with
      DNA networks.
AB  - During the renaturation of DNAs large networks build up which cannot be eluted
      from hydroxyapatite under standard fractionation conditions (60 degrees C, 0.5 M
      PB). This is a serious problem especially in plant-DNA renaturation studies as
      hyperpolymers may comprise more than half of the renatured DNA mass even at
      moderately long initial fragment lengths and low C0t values. Utilizing the acid
      solubility of hydroxyapatite a method is outlined which will recover the total
      double-stranded DNA fraction and will prepare the column for the next
      fractionation in one quick operation. As the method is time saving compared to
      the standard hydroxyapatite fractionation procedure its general application may
      prove to be useful.

PMID- 9762085
TI  - Preparation of lipid-free protein extracts of egg yolk.
AB  - 1-Butanol extraction of chicken egg yolk homogenates containing 1 M NaCl yields
      lipid-free aqueous solutions of egg yolk proteins. These solutions, after
      dialysis, can be applied to a variety of chromatographic media without clogging.
      Although some proteins are denatured by this procedure, most of the water-soluble
      proteins remain in solution, including biotin-binding protein and riboflavin
      binding protein.

PMID- 9762086
TI  - Assay of delta-aminolevulinic acid synthetase in homogenates of mouse, rat, and
      human liver: species differences in requirement for an exogenous succinyl-CoA
      generating system.
AB  - Conditions required for optimal assay of low levels of activity of hepatic delta
      aminolevulinic acid synthetase have been studied, comparing dilute homogenates of
      mouse, rat, and human livers. The assay method used was a modification of that
      described by Ebert et al. (Biochim, Biophys, Acta (1970) 208, 236-250), and
      livers were studied from both untreated animal and human subjects and subjects
      pretreated with porphyrinogenic compounds. In homogenates of mouse and human but
      not rat liver, maximal rates of delta-aminolevulinic acid formation required
      addition to the incubation mixture of an exogenous system for succinyl-CoA
      generation. The requirement for this generating system was increased if livers
      from pretreated subjects were frozen and stored prior to assay, suggesting that
      the endogenous capacity for succinyl-CoA generation was more labile than delta
      aminolevulinic acid synthetase under these conditions. Of the metabolic
      inhibitors tested (F-, malonate, and arsenite), only F- (100 mM final
      concentration) enhanced activity. Increasing the permeability of mitochondria by
      quick freeze-thawing of fresh homogenates just before assay did not increase the
      rate of delta-aminolevulinic acid formation.

PMID- 9762087
TI  - Chromatographic separation and automated analysis of flavanols.
AB  - Flavanols from barley or hops were separated chromatographically and assayed
      automatically by reaction with the chromogen, 4-dimethylaminocinnamaldehyde. For
      separating the flavanols on Sephadex G-25, gradient elution with water-methanol
      mixtures was necessary. The chromogen was specific for flavanols and well suited
      to AutoAnalyzer methods. The method appears generally applicable in flavanol
      analysis of plant materials.

PMID- 9762088
TI  - The resolution of membrane proteins based upon size, charge, and hydrophobicity.
AB  - Currently available systems for resolving membrane proteins are based only on
      size and charge differences. Recently, it has been shown that Triton-urea-acetic
      acid gels which separate proteins on the basis of charge, size and hydrophobicity
      are capable of resolving proteins differing only by the substitution of a single
      neutral amino acid. We have applied this new method to the resolution of
      bacterial envelope proteins. Conditions for optimal resolution of different
      bacterial envelope proteins were determined by electrophoresis through transverse
      urea and Triton X-100 gradient gels. We have also correlated the components
      resolved in this system with those resolved by classical sodium dodecyl sulfate
      gel electrophoresis by using two-dimensional slab gels combining the two systems.
      Furthermore, envelope protein fractions from different species and strains of
      bacteria were compared to identify specific proteins. This system appears to be a
      promising method for investigating envelope proteins which are due to missense
      mutations.

PMID- 9762089
TI  - Chromatographic purification of soluble elastin.
AB  - An improved method for extraction and purification of soluble elastin from aortas
      of copper-deficient swine has been devised. It depends upon the use of both
      acidic and neutral protease inhibitors during preparation. Collagen is first
      precipitated with acetic acid. A two-step separation and purification of elastin
      from the collagen-free extract is based on absorption of the acidic proteins on
      DEAE-cellulose and gel filtration through agarose. The protein recovered is
      homogeneous by gel electrophoresis. It has the molecular weight (75,000) and
      amino acid composition of the soluble elastin from the same source prepared by
      repeated coacervation.

PMID- 9762090
TI  - A volume adapter for use in a B-XIV zonal rotor.
AB  - A simple adapter for reducing the chamber volume of B-XIV-type rotors is
      described. The adapter consists of a disk-like body, which occupies the lower
      part of the rotor chamber, and an aluminum sleeve with four septa. The modified
      rotor has a volume of 272 ml and has proved very suitable for rate-sedimentation
      analysis of small amounts of biological material. The modified rotor is operated
      as is a standard B-XIV rotor.

PMID- 9762091
TI  - A modified orcinol test for the specific determination of RNA.
AB  - The standard orcinol test for estimating RNA is modified and developed as a
      specific method for the determination of RNA in the presence of DNA and proteins.
      The main differences in the procedure of the modified test when compared to that
      of the standard test are preincubation of the samples with H2SO4 before addition
      of the orcinol reagent, decreased concentration of orcinol, no addition of
      FeCl3.6H2O, and quantitation of RNA at its maximum absorbance under these
      conditions at 500 nm where interferences from DNA and proteins were minimal.

PMID- 9762092
TI  - Preparation, isolation, analysis, and characterization of 3-benzo[a]pyrenyl-beta
      D-glucopyranosiduronic acid: a metabolite of 3-hydroxybenzo[a]pyrene with
      potentially high carcinogenic activity.
AB  - The aglycone, 3-hydroxybenzo[a]pyrene, was metabolized to 3-benzo[a]pyrenyl-beta
      D-glucopyranosiduronic acid in the presence of uridine 5'-diphosphoglucuronic
      acid and rabbit liver microsomes. The course of the biosynthetic reaction was
      followed by fluorimetry and reverse-phase, paired-ion high pressure liquid
      chromatography (HPLC). Also, the HPLC system was used to analyze for glucuronide
      and 3-hydroxybenzo[a]pyrene during the isolation procedure. The existence of a
      glucuronide of 3-hydroxybenzo[a]pyrene was determined by radiotracer and enzymic
      techniques, utilizing the HPLC system. Field desorption and direct inlet mass
      spectral techniques were used to characterize the 3-hydroxybenzo[a]pyrene
      glucuronide.

PMID- 9762093
TI  - Quantitation of human globin chain synthesis by cellulose acetate
      electrophoresis.
AB  - We have developed a method for the separation and quantitation of human alpha-,
      beta-, and gamma-globins utilizing cellulose acetate electrophoresis. The
      relative rates of synthesis of globin chains in reticulocytes in peripheral blood
      is determined by: (i) incubating intact cells with [35S]methionine; (ii)
      preparing globin from the hemolysates; (iii) performing electrophoresis of the
      globin on cellulose acetate strips; and (iv) autoradiography or direct
      determination of the radioactivity incorporated into each globin chain. The
      method is simple and rapid, requires only small amounts of hemolysate (30
      micrograms of globin), and provides excellent resolution and reproducible
      quantitation of alpha-, beta A-, beta S-, and gamma-globin chains for up to 24
      peripheral blood samples at one time. Measurements by this method in patients
      with thalassemia variants and sickle-cell disorders correlate well with analysis
      of the same samples by carboxymethyl cellulose chromatography. This methodology
      may permit more widespread analysis of globin synthesis in the thalassemia
      syndromes and may also be useful in the analysis of globins synthesized from
      human globin mRNA in cell-free systems.

PMID- 9762095
TI  - Protoheme extraction from plant tissue.
AB  - A method for reproducibly estimating the protoheme content of plant tissues has
      been developed. The tissue sample is homogenized in 80% acetone to remove
      pigments and lipids; protoheme is then extracted from the tissue residue with 2%
      HCl in acetone and quantitatively transferred into diethyl ether. After
      evaporation of the ether, the residue is dissolved in alkaline pyridine, and the
      protoheme concentration is estimated from a dithionite-reduced-minus-ferricyanide
      oxidized spectrum. When compared to some other methods, this procedure gives
      consistently higher yields.

PMID- 9762094
TI  - The enzymic synthesis of beta-[32P]UDP-N-acetylglucosamine.
AB  - Cells of Micrococcus sp. 2102 incorporate inorganic [32P]phosphate from the
      medium into the sugar-phosphate polymer of the wall. Controlled acid hydrolysis
      of sodium dodecyl sulphate-extracted cells gives N-acetylglucosamine 6-[32P]
      phosphate which can be purified by ion-exchange chromatography and incubated with
      UTP in the presence of crude preparations of phosphoacetylglucosamine mutase from
      Neurospora crassa and UTP:N-acetylglucosamine 1-phosphate phosphotransferase from
      Bacillus licheniformis which act in concert to synthesise beta-[32P]UDP-N
      acetylglucosamine.

PMID- 9762096
TI  - Measurement of polyadenylic acid by hybridization with polyuridylic acid: a
      source of error due to the lability of tritiated polyuridylic acid in
      trichloroacetic acid.
AB  - During brief exposure to trichloroacetic acid at 0 degree C, significant amounts
      of tritiated polyuridylic acid are converted to acid-soluble products. The loss
      of polymeric radioactivity is dependent on both acid concentration and the time
      of exposure to acid. When trichloroacetic acid precipitation is used to recover
      the tritiated polyuridylic acid present in a hybrid with polyadenylic acid,
      significant underestimates of the hybridized radioactivity can occur because of
      the lability of tritiated polyuridylic acid. Conditions are given which minimize
      the lability and permit quantitative recovery of tritiated polyuridylic acid by
      trichloroacetic acid precipitation.

PMID- 9762097
TI  - A simple method for the elimination of amine contaminants in buffers for single
      column amino acid analysis in physiological samples at picomole levels.

PMID- 9762099
TI  - A rapid method for the isolation of intracytoplasmic membranes from
      Rhodopseudomonas sphaeroides using an air-driven ultracentrifuge.
AB  - A method has been developed for the isolation intracytoplasmic (ICM) vesicles
      (chromatophores) from Rhodopseudomonas sphaeroides using an air-driven
      ultracentrifuge. Application of conventional techniques used for preparative
      scale equipment to the air-driven ultracentrifuge allows the rapid isolation of
      ICM vesicles from reduced quantities of starting material. Sodium dodecyl
      sulfatepolyacrylamide gel electrophoresis profiles of ICM vesicles isolated in
      this fashion are essentially indistinguishable from those isolated by
      conventional means.

PMID- 9762098
TI  - Action of endo-alpha-N-acetyl-D-galactosaminidase on synthetic glycosides
      including chromogenic substrates.
AB  - The synthetic glycosides, p-nitrophenyl- and o-nitrophenyl-2-acetamido-2-deoxy-3
      O-beta-D-galactopyranosyl-alpha- D-galactopyranosides, were found to be effective
      chromogenic substrates for an endo-alpha-N-acetyl-D-galactosaminidase. We did not
      experience any problems when these substrates were used for the screening of
      column fractions during the purification of the endoenzyme from Diplococcus
      pneumoniae culture filtrates. However, it should be pointed out that a
      combination of exo-beta-galactosidase, capable of cleaving beta 1-->3 linkages,
      and an exo-alpha-N-acetyl galactosaminidase would also liberate nitrophenol from
      the above substrates. The enzyme had no action on several other synthetic
      glycosides tested indicating the strict specificity of this enzyme for the
      disaccharide Gal beta-->GalNAc linked via an alpha-linkage to the aglycone. The
      enzyme was inactive when the aglycone was methanol but shows activity against the
      glycosides of phenol, nitrophenols, serine, and threonine. The use of p
      nitrophenyl-2-acetamido-2-deoxy-3-O-beta -D-galactopyranosyl-beta-D
      galactopyranoside, which is a competitive inhibitor of the endoenzyme, as an
      affinity ligand for the purification of the enzyme is described.

PMID- 9762100
TI  - Automatic collector of expired 14CO2 for liquid scintillation counting.
AB  - A filtration technique was employed to trap 14CO2 continuously for liquid
      scintillation counting. Devices for delivering scintillator and ethanolamine
      solutions were combined symmetrically with two fritted-glass aspirators for
      alternating operation. The collector was regulated by a fraction collector timer.
      Trial and animal tests indicated that the described method was efficient,
      reliable, and more convenient for frequent collection over long periods than
      alternative methods. The automatic collector was used for metabolic studies of [1
      14C] arachidonic acid in rats kept in metabolic cages and the results were
      processed by multicompartmental analysis.

PMID- 9762101
TI  - Direct physical measurements on substituted agarose gels: evidence for
      intercalation of gel-bound ethidium into transfer RNA.
AB  - The cation of the salt ethidium bromide (3,8-diamino-5-ethyl-6
      phenylphenanthridinium bromide) has been covalently linked to an agarose matrix
      through an intermediate 3,3'-diaminodipropylaminosuccinyl spacer arm. Partition
      binding and visible absorption spectral measurements on the gel were used to
      monitor the binding of transfer RNA to the covalently bound ethidium group.
      Direct fluorescence measurements of the formation of the gel-bound complex
      indicate that this binding involves the intercalation of the ethidium groups into
      the tRNA molecule. Dissociation of the ethidium-tRNA complex was monitored as a
      function of sodium chloride concentration by both direct solution spectral
      measurement of the released tRNA and by fluorescence quenching measurements of
      the dissociation of the intercalation complex. The derivatized gel has been shown
      to be capable of the fractionation of tRNA species by elution with a positive
      salt gradient under column flow conditions.

PMID- 9762102
TI  - Mercury contamination during pH measurement and its effect on creatine kinase
      activity.
AB  - Inhibition of activity of the enzyme creatine kinase occurs when small volumes of
      assay mixtures have their pH measured using a combination pH electrode prior to
      addition of the enzyme. This inhibition can be attributed to diffusion of ionic
      mercury from the calomel reference electrode through the saturated potassium
      chloride salt bridge and the ground glass-liquid junction to the test solution.
      The concentration of mercury accumulating in a solution by this process can be
      sufficient to affect the activity of an enzyme, and EDTA cannot be used
      successfully to scavenge mercury ion and avoid the inhibition.

PMID- 9762103
TI  - Removal of sodium dodecyl sulfate from proteins.
AB  - Effective removal of sodium dodecyl sulfate from proteins in water or sodium
      phosphate buffer was achieved by column chromatography using the ion-retardation
      resin AG11A8. An average recovery of 83% protein was obtained, while 0.1 to 1.4
      moles of sodium dodecyl sulfate remained on each mole of protein.

PMID- 9762104
TI  - N-thiobenzoylsuccinimide as thioacylating reagent in the sequential analysis of
      peptides by the solid phase technique.
AB  - N-Thiobenzoylsuccinimide is synthesized and proposed as a new thioacylating
      reagent. Its use in sequential solid phase degradation of peptides is examined.

PMID- 9762105
TI  - Determination of acetaldehyde in rat blood by the use of rat liver aldehyde
      dehydrogenase.
AB  - A method has been developed for the determination of low concentrations of
      acetaldehyde in rat blood. The method involves extraction of blood in perchloric
      acid followed by a fluorimetric determination of acetaldehyde in neutralized
      extracts by the use of a low K(m) aldehyde dehydrogenase isolated from rat liver
      mitochondria. Acetaldehyde concentrations down to 2 to 3 microM could be detected
      in blood samples of 0.1 ml containing high concentrations of ethanol (10-40 mM).
      Due to its simplicity, sensitivity, and the use of a low-cost fluorimeter, this
      enzymatic method should be a valuable complement to gas chromatographic methods
      for acetaldehyde determination.

PMID- 9762106
TI  - The characterisation of thiobarbituric acid reactivity in human plasma and urine.
AB  - The specificity of the thiobarbituric acid reaction (TBA) has been investigated
      using techniques of high-performance thin-layer chromatography and
      spectrofluorimetry. It was found that malondialdehyde (MDA) derived from
      different lipid and nonlipid origins formed the same MDA-TBA complex. This
      complex could be separated from other TBA-reactive compounds by both
      chromatography and spectrofluorimetry. Normal human plasma and urine both formed
      an MDA-TBA complex along with other TBA-reactive compounds. In plasma this was
      associated mainly with phosphatidylcholine and appeared to be peroxidic in
      reaction. Urine, however, contained polar MDA-forming compounds probably
      resulting from the oxidation of 2-deoxyaldoses during the acid-heating stage of
      the TBA test.

PMID- 9762107
TI  - Assessment of counting efficiencies for labeled protein and other macromolecules
      in filter disk assays.
AB  - A several-fold greater counting efficiency is observed for protein labeled with
      [3H]leucine than for free [3H]leucine using a conventional filter disk assay. A
      similar, though less marked, effect is noted for 14C-labeled molecules. These
      results are comparable to those reported by others for counting efficiencies of
      labeled DNA and deoxynucleotides and illustrate the generality of this effect
      with regard to macromolecules and their low-molecular weight precursors. This
      phenomenon, presumably due to differences in the distribution of large and small
      molecules within filters, gives rise to errors in the quantitation of
      macromolecule synthesis if a counting efficiency identical to that of the
      precursor is assumed to apply. A convenient method for determining counting
      efficiencies of various molecules bound to filters is presented which eliminates
      this problem.

PMID- 9762108
TI  - Automated analysis of common basic amino acids, mono-, di-, and polyamines,
      phenolicamines, and indoleamines in crude biological samples.
AB  - A fully automated, fast, and sensitive method for the separation of common basic
      amino acids and mono-, di-, and polyamines as well as phenolic- and indoleamines
      is described. Picomole level determination of hydroxytryptophan, tryptophan,
      histidine, lysine, ethanol amine, arginine, noradrenaline, diaminopropane,
      putrescine, histamine, cadaverine, dopamine, hexamethylenediamine, agmatine,
      tyramine, phenethylamine, serotonin, 5,6-dihydroxytryptamine, 5
      methoxytryptamine, tryptamine, spermidine, and spermine is carried out by ion
      exchange column chromatography on a single sample in 170 min of total analysis.
      This method is well suited for crude extracts without preliminary purification,
      thus reducing preparative losses. The reproducibility of the method has been
      studied and the percentage recovery of the different compounds after column
      chromatography is reported. Its application to crude samples from different
      biological sources such as microorganisms, vegetables, platelets, and urine is
      presented. This method could serve as a powerful tool for the analysis of these
      amino compounds in which there is currently a considerable interest.

PMID- 9762109
TI  - Staphylococcal protein A-sepharose columns and the characterization of measles
      virus-specific polypeptides in persistently infected cells.
AB  - Viral polypeptides in extracts prepared from [35S]methionine-labeled human
      epithelial carcinoma cells persistently infected with measles virus were reacted
      with virus-specific antisera. Microcolumns of staphylococcal protein A linked to
      Sepharose were used to isolate antigen-antibody complexes that contained few
      contaminating host polypeptides. Measles virus polypeptides in these complexes
      could be identified readily on sodium dodecyl sulfate-polyacrylamide gels even
      when antiserum with low reactivity toward the viral antigens was used.

PMID- 9762110
TI  - Analytical micro-preparative electrophoresis: quantitation of phosphoglucose
      isomerase isoenzymes.
AB  - A simple micro-preparative electrophoresis apparatus is described using a thin
      vertical slab gel and continuous elution through a narrow horizontal slot.
      Phosphoglucose isomerase (PGI) isoenzymes in lysates of 0.2 to 100 microliters of
      erythrocytes were separated using this system and their activities determined
      using an on-line, air-segmented, continuous flow assay. Ninety-five percent
      recovery of the separated isoenzymes after electrophoresis was achieved and the
      factors influencing recovery of PGI and hemoglobin were investigated. Thus,
      quantitative recovery has been achieved without any loss of resolution. Up to 29
      successive separations of PGI isoenzymes have been carried out on a single gel.

PMID- 9762111
TI  - Vitamin D3 in plasma: quantitation by mass fragmentography.
AB  - Combined gas chromatography-mass spectrometry with multiple-ion detection is used
      to quantitate vitamin D3 in plasma samples. Extensive cleanup of the plasma
      extract prior to analysis is required before mass fragmentographic analysis is
      possible, i.e., solvent extraction, digitonin precipitation, Lipidex column
      chromatography, and derivatization. Low resolution mass fragmentography is
      performed by monitoring simultaneously the molecular ions of the
      heptafluorobutyric esters of the all-trans isomer of vitamin D3 and
      dihydrotachysterol2, which is used as an internal standard. This new method uses
      5 ml of plasma and it is specific and sensitive to 600 pg of vitamin D3. This
      assay shows that in plasma of normal adult subjects there is a vitamin D3
      concentration of 5 to 11 ng/ml, lower than those values reported for biological
      and competitive protein binding assays. Specifically the method described offers
      potential as an eventual reference method.

PMID- 9762112
TI  - A new method for allantoin determination and its application in allantoin
      determination in Agrostemma githago L. Seed.
AB  - We have established several optimal conditions for qualitative and quantitative
      allantoin determination by applying Ehrlich's reagent. The limit of detection for
      allantoin determination amounts to 5 x 10(-6) mM. Allantoin is determined
      quantitatively by measuring the absorbance at 440 nm (from 300 to 1000
      micrograms/ml). The color of the complex becomes stable by standing for 10 min at
      room temperature. We have used these conditions for allantoin determination in
      Agrostemma githago seed.

PMID- 9762113
TI  - Numerical analysis of thermal denaturation of nucleic acids.
AB  - Denaturation of DNA molecules by stepwise incrementation of the temperature leads
      to melting profiles showing a fine structure, composed of individual melting
      modes. A method is described by which quantitative physical information brought
      by the modes can be extracted from the melting profile. Related problems such as
      data editing and smoothing are also discussed.

PMID- 9762114
TI  - Sources of error in the channels ratio method for efficiency determination in
      liquid scintillation counting.
AB  - The reliability of the channels ratio method for determining counting efficiency
      in liquid scintillation counting was investigated. It was found that the
      efficiency of counting gels, cloudy samples, two-phase samples, samples in which
      the radioactive material was precipitating, and samples on solid supports could
      not be reliably determined from a normal quench correction curve. A curve
      constructed from external standard channels ratios was unreliable when mixing
      different vial sizes and sample volumes, but one constructed from sample channels
      ratios was not. It was also found that variation in instrument performance can
      result in large errors unless samples and standards are counted together.
      Statistical error changed relatively little within the range of ratios 0.3 to
      0.8.

PMID- 9762115
TI  - A further modified tissue homogenizer.

PMID- 9762116
TI  - Characterization of density gradients prepared by freezing and thawing a sucrose
      solution.
AB  - Density gradients of sucrose can be prepared in large numbers by successive
      freezing and thawing of sucrose solutions. Gradients of other solute molecules,
      such as salt and detergents, also form and this could affect subsequent
      sedimentation behavior of some molecules. However, the sedimentation behavior of
      native and denatured DNA of bacteriophage lambda was essentially isokinetic under
      the conditions used thus making these gradients comparable with ones prepared
      manually, at least for preparative sedimentation work with nucleic acids.

PMID- 9762118
TI  - Quantitation of nanogram amounts of protein using [3H]dinitrofluorobenzene.

PMID- 9762117
TI  - A simplified procedure for organic phosphorus determination from phospholipids.
AB  - We describe an improved method for the determination of organic phosphorus from
      phospholipids. It is the combination of a very fast mineralization step followed
      by the estimation of liberated phosphate by means of malachite green. This method
      is accurate, simple, and sensitive.

PMID- 9762119
TI  - Zone collector and transfer device for thin-layer chromatography.

PMID- 9762120
TI  - Automated assay of glycosidases.
AB  - The Technicon Basic Auto Analyzer sampler system was modified for simultaneous
      sampling of glycosidase(s) and substrate-buffer solutions. The inexpensive
      modification allows performance of automated enzyme analyses and enzyme kinetic
      studies with minimal consumption of substrate and/or enzyme.

PMID- 9762121
TI  - A simple procedure for regeneration of an organomercurial agarose column.

PMID- 9762122
TI  - An improved synthesis of malonyl-coenzyme A.
AB  - A method for the synthesis of [14C]malonyl-Coenzyme A starting with 10 mumol of
      [14C]malonate is reported. The synthesis is accomplished with yields of 48 +/- 4%
      (1 sigma, n = 6) using a procedure which does not require the isolation or
      purification of any intermediates.

PMID- 9762123
TI  - A program which automatically quantitates gel electrophoretic autoradiograms.
AB  - The use of a computer-coupled film scanner to measure and analyze autoradiograms
      of gel electropherograms is described. A program has been written which fits
      Gaussian curves to the complex band pattern that constitutes a density profile
      without the need for estimated parameters in the input. The great majority of the
      fits are satisfactory. This program, which is written in FORTRAN, runs on a
      small, inexpensive computer. Another program which approximates a Gaussian least
      squares fit has been run for comparison; this procedure can also be used to
      refine occasional unsatisfactory fits. Finally, a program has been written which
      sums the density profile within specified limits, so that the integrated
      intensities of bands due to isolated protein components may be found.

PMID- 9762124
TI  - Automated activation energy.
AB  - A method and equipment used for automated determination of activation energies on
      a single sample are described. Essentially identical results are obtained in both
      automated and manual methods. The automated method is particularly valuable for
      minimizing the amounts of enzyme, substrate, and time required. Further, errors
      in repetitive pipetting and calculation are eliminated.

PMID- 9762125
TI  - A single-column amino acid analysis method which resolves hexosamines and several
      cysteine derivatives.
AB  - A single-column amino acid analysis method is presented for use in structural
      studies of glycoproteins. The system gives excellent resolution of glucosamine,
      galactosamine, cysteic acid, CM-cysteine, AE-cysteine, the internal standard
      norleucine, and all amino acids normally present in protein hydrolysates.

PMID- 9762126
TI  - Chromatographic determination of angiotensin-converting enzyme and angiotensinase
      activity.
AB  - An analytical method utilizing an automatic amino acid analyzer is described for
      the separation, identification, and measurement of 5 to 50 nmol of angiotensin I,
      angiotensin II, [Des-Phe8]angiotensin II, Phe-His-Leu, His-Leu, isoleucine,
      leucine, tyrosine, and phenylalanine. Aminex A-5 cation-exchange resin (0.9 x 15
      cm) is sequentially eluted with three sodium citrate buffers: pH 3.25, 0.2 N; pH
      4.85, 0.54 N, and pH 6.5, 0.39 N at 60 and 80 degrees C. Reaction with ninhydrin
      is used for detection. This chromatographic system was used to determine
      angiotensin-converting enzyme activity and the angiotensinase activity of rabbit
      brain endopeptidase B. In each assay, the unhydrolyzed substrate and both
      products were measured simultaneously in one step without pretreatment of the
      hydrolysate. Products were recovered in 1:1 molar ratios and the overall recovery
      of an hydrolyzed substrate of products was quantitative.

PMID- 9762127
TI  - A new, fast, and very sensitive bioluminescence assay for phospholipases A and C.
AB  - A new, simple, and very sensitive assay for phospholipase A and C is described.
      The assay is based on the bioluminescence developed by the mutant of the
      bacterium Beneckea harveyi as a response to myristic acid released from
      dimyristoyl phosphatidylcholine by either phospholipase A or by a phospholipase C
      lipase coupled system. It is possible to assay these enzymes at a rate
      corresponding to a release of as little as 1 to 2 pmol of myristic acid per
      minute.

PMID- 9762128
TI  - Isolation of circular viral and complementary strand DNA from bacteriophage f1
      duplex replicative-form DNA.
AB  - A general method has been developed for the large scale isolation of intact,
      circular, single-stranded DNA molecules of each strand from supercoiled duplex
      DNA. The method involves the conversion of the supercoiled duplex DNA to singly
      nicked, relaxed duplex DNA; denaturation of the duplex DNA; separation of
      circular DNA molecules from linear DNA molecules; and separation of circular plus
      and minus strands. All separations involve zone sedimentation. No isopycnic
      gradient centrifugation is required. The last step in the purification, the
      separation of plus and minus strands, can be easily adapted for small scale
      analytical measurements of the amounts of plus and minus strand DNA.

PMID- 9762129
TI  - Analytical techniques for cell fractions. XXIII. A stable thermal gradient device
      for heat denaturation studies on proteins.
AB  - The ISO-DALT two-dimensional electrophoretic system (1,2), based on the method of
      O'Farrell (3), is capable of performing large numbers of analysis on complex
      mixtures of proteins. However, both separations employed are carried out under
      dissociating or denaturing conditions and no enzyme activities are readily
      observable in the analyzed proteins. In order to identify the spots corresponding
      to particular enzymes, it is therefore necessary to employ some nondestructive
      resolving technique first and as a second step to perform both enzyme and two
      dimensional electrophoretic analyses on the fractions generated. By correlating
      enzyme activity with intensity of various spots on the two-dimensional gels
      throughout the series of initial fractions, identifications, can be made. This
      approach, unlike the more direct immunoprecipitation methods (4), requires the
      running of large numbers of enzyme analyses and two-dimensional gels and some
      convenient initial resolving procedure. Convenient and rapid techniques for the
      analyses (5,6) and gels (1,2) have been described previously in this series and
      elsewhere. This paper deals with the use of selective denaturation in a
      temperature gradient as an initial resolving procedure and describes a simple
      thermal gradient device for generating such a gradient.

PMID- 9762130
TI  - Purification of small peptides labeled with Bolton-Hunter reagent.
AB  - A method utilizing high-voltage electrophoresis on paper is described whereby a
      pentapeptide (Asp-Ser-Asp-Pro-Arg) labeled with Bolton-Hunter reagent is
      separated from hydrolyzed reagent and unreacted peptide and is recovered from the
      electrophoretogram in high yield. The general applicability to other peptides is
      discussed.

PMID- 9762131
TI  - An improved assay for hexokinase activity in human tissue homogenates.
AB  - An improved method has been developed for the assay of hexokinase (EC 2.7.1.1)
      levels in human tissue homogenates. The enzyme is quantitated by the
      spectrophotometric measurement, at 340 nm, of NADPH formed according to the
      reaction scheme: [formula: see text] In tissue homogenates a number of enzymes
      are present which can interfere with the assay by reacting with substrates or
      products of the assay reactions. In the described procedure hexokinase is assayed
      directly in homogenates under conditions in which the effect of possible
      contaminating enzymes (glucose dehydrogenase, EC 1.1.1.47; glucose 6-phosphatase,
      EC 3.1.3.9; glucose phosphate isomerase, EC 5.3.1.9; 6-phosphogluconate
      dehydrogenase EC 1.1.1.44; and NADP-reducing enzymes) are eliminated. Precision
      studies on the assay gave within-day reproducibility of 4.3% (CV) on a tissue
      having a mean activity of 1.68 U/g of tissue, and day-to-day variability of 15%
      (CV) for a tissue averaging 1.83 U/g of tissue.

PMID- 9762132
TI  - An agarose gel electrophoretic method for analysis of sulfated glycosaminoglycans
      of cultured cells.
AB  - Agarose disc gel electrophoresis has been adapted to achieve the separation of
      the major sulfated glycosaminoglycans produced by cells in culture. By use of
      buffers containing barium ion, mixtures of chondroitin sulfate, dermatan sulfate,
      and heparan sulfate are well resolved into discrete bands. The technique can be
      used preparatively as well as analytically to separate quantities of
      glycosaminoglycans up to a milligram in a 6-mm diameter gel.

PMID- 9762133
TI  - A simplified polyacrylamide gel electrophoresis apparatus for simultaneous
      application of multiple buffer systems or detergent combinations.
AB  - A previous design of an apparatus for the simultaneous fractionation by
      polyacrylamide gel electrophoresis in 10 different buffer systems (1) was
      replaced by a greatly simplified new design, employing small, cylindrical buffer
      partitions within the lower buffer reservoir and/or upper buffer reservoir of a
      conventional, temperature-regulated polyacrylamide gel electrophoresis apparatus
      for cylindrical gels. The apparatus was tested in application to the problem of
      simultaneous polyacrylamide gel electrophoresis in different buffer systems with
      the purpose of optimizing the operative pH for a particular fractionation
      problem. It was also applied to fractionations in a single buffer system to which
      various combinations of ionic and nonionic detergents were admixed.

PMID- 9762134
TI  - Quantitation of methionyl peptides in nanomole quantities by a fluorometric
      method.
AB  - A quantitative and highly specific method to determine low concentrations of
      methionyl peptides, which do not contain tryptophan or cysteine residues, has
      been developed. The method is based on the stoichiometry and selectivity of N
      chlorosuccinimide (NCS) towards methionine and N-acetyltryptophan. N
      Chlorosuccinimide reacts with N-acetyltryptophan in a 1:1 ratio to produce the N
      acetyl-2-oxindolealanine--a derivative essentially devoid of fluorescence. The
      decrease in fluorescence intensity is approximately linear with respect to the
      NCS concentration. Preincubation of NCS with methionine or methionyl peptide
      consumes a stoichiometric amount of the reagent and the unreacted NCS is
      quantitated by the decrease in fluorescence intensity resulting upon incubation
      of the mixture with 1 eq of N-acetyltryptophan. Less than 1 nmol of methionyl
      peptide can be accurately quantitated by this method.

PMID- 9762135
TI  - Synthesis of UDP-N-[1-14C]acetyl D-glucosamine and UDP-N-[1-14C]acetyl-D
      galactosamine from [1-14C]acetate.
AB  - Procedures for the preparation of UDP-N-[1-14C]acetyl-D-glucosamine and UDP-N-[1
      14C]acetyl-D-galactosamine with very high specific activities are described. The
      overall yield based on the amount of [1-14C]acetate used is greater than 80%. The
      N-acetyl-D-glucosamine-alpha-1-phosphate used in this synthesis is prepared by
      phosphorylation of tetraacetyl-D-N-acetylglucosamine with crystalline phosphoric
      acid. N-acetyl-D-glucosamine-alpha-1-phosphate is then deacetylated in anhydrous
      hydrazine with hydrazine sulfate as a catalyst. D-glucosamine-alpha-1-phosphate
      is N-acetylated with [14C]acetate using N-ethoxycarbonyl-2-ethoxy-1,2
      dihydroquinoline as the coupling agent. The acetylated product is coverted to the
      UDP derivative with yeast UDP-N-acetyl-D-glucosamine pyrophosphorylase. UDP-N-[1
      14C]acetylgalactosamine is prepared by acetylation of UDP-galactosamine using [1
      14C]acetate and N-ethoxy-carbonyl-2-ethoxy-1,2-dihydroquinoline. UDP
      galactosamine is prepared enzymatically using galactokinase and galactose-1
      phosphate uridyltransferase. The labeled products, isolated and characterized by
      ion-exchange and paper chromatography, were active as substrates in glycosyl
      transferase systems.

PMID- 9762136
TI  - Comparison of dark-field and bright-field incident illumination for in vivo
      measurements of reduced pyridine nucleotides.
AB  - Bright-field and dark-field illumination techniques for in vivo measurements of
      reduced pyridine nucleotide fluorescence were compared in 15 rats during periods
      of normocapnia, hypocapnia, hypercapnia, and anoxia. Parameters investigated
      included fluorescence, cortical reflectance, cortical blood flow, and
      electroencephalograms. In normal brain, with preserved autoregulation, reduced
      pyridine nucleotide fluorescence was constant through a wide range in Pa(CO2),
      cortical blood flow, and cerebral blood volume in animals studied using vertical
      illumination (bright-field) techniques. There was a marked increase in reduced
      pyridine nucleotide fluorescence at death from anoxia. Artifacts were reduced by
      monochromators for excitation, emission, and reflected light; low-intensity
      vertical excitation energy and high-sensitivity recording instrumentation; and a
      small avascular (123 microns) field. Potential sources of error include
      photodecomposition, hemoglobin interference from absorption and reflectance, and
      light scattering. Vertical excitation techniques using a small field appeared to
      give more reliable and reproducible results than circumferential techniques using
      a larger field of observation.

PMID- 9762137
TI  - Quantitative Limulus lysate assay for endotoxin activity: aggregation of
      radioiodinated coagulogen monomers.
AB  - This communication describes a modification of the Limulus lysate assay which
      allows precise quantitation of picograms of bacterial lipopolysaccharide
      activity. The method measures the incorporation of 125I-labeled coagulogen
      monomers into the lysate clot as a function of lipopolysaccharide concentration.
      The method is more precise and requires less lysate than the previously described
      quantitative assays for endotoxin activity.

PMID- 9762138
TI  - Measurement of S-adenosyl-L-methionine levels by SP Sephadex chromatography.
AB  - Cation-exchange chromatography with sulfopropyl Sephadex was used to measure the
      levels of S-[methyl-3H]adenosyl-L-methionine synthesized by L1210 cells in vitro.
      Separation of S-[methyl-3H]adenosyl-L-methionine from [methyl-3H]methionine and
      other metabolites was achieved by stepwise elution with varying concentrations of
      HCl.

PMID- 9762139
TI  - S1 nuclease-specific nicking of mitochondrial DNA containing displacement loops.
AB  - Conditions are described in which the single strand-specific nuclease S1
      selectively nicks mitochondrial DNA containing displacement loops without nicking
      supercoiled mitochondrial DNA. Using these conditions, the percentage of
      molecules containing displacement loops can be easily and accurately determined.
      This method is superior to the traditional electron microscopic examination for
      assessing the frequency of displacement loop-containing molecules. In addition,
      this method permits the determination of the relative specific activities of
      displacement loop and nondisplacement loop-containing mitochondrial DNA after
      various radioactive labeling protocols. S1 nuclease is shown to cleave the
      displaced strand of the displacement loop, to partially degrade the 7S-initiation
      strand, but not to cleave the parental template strand complementary to the 7S
      initiation strand. The final product is a nicked circular molecule with at least
      two breaks localized within the displacement loop region in only one of the two
      parental strands.

PMID- 9762140
TI  - The effect of thiodiglycol and dithiothreitol on the alkaline hydrolysis products
      of certain amino acid phenylthiohydantoins.
AB  - The thiazolinone and phenylthiohydantoin derivatives of most amino acids can be
      hydrolyzed with alkaline dithionite to generate the free amino acid. The
      acidification of this hydrolysate with 3 N HCl containing thiodiglycol leads in
      the case of glutamic acid, glutamine, aspartic acid, asparagine, and S-carboxy
      methylcysteine to the generation of ninhydrin-reacting components having the
      chromatographic properties of other amino acids. The use of dithiothreitol
      instead of thiodiglycol appears to be more satisfactory in most instances.

PMID- 9762142
TI  - The determination of similarities in amino acid composition among proteins
      separated by two-dimensional gel electrophoresis.
AB  - A simple and rapid procedure has been developed to determine similarities in
      amino acid composition among cellular proteins separated by two-dimensional gel
      electrophoresis. Cells in tissue culture are simultaneously labeled with two
      different amino acids each tagged with a different radioisotope. The proteins are
      then separated on two-dimensional gels and their location on the gels determined
      by Coomassie-blue staining or autoradiography. Elution of the protein from the
      appropriate region of the gel followed by liquid scintillation counting yields an
      isotope ratio which reflects the ratio of the two amino acids in the protein.
      Examples of the use of this technique in analyzing mutant proteins, proteins
      altered by carbamylation, and cell proteins with similar amino acid composition
      (e.g., actin and tubulin) are given.

PMID- 9762141
TI  - Separation of acetic and propionic acid analogs of L-thyroxine and L
      triiodothyronine by thin-layer chromatography.
AB  - A thin-layer chromatographic method is described for the separation of the acetic
      and propionic acid analogs of thyroxine and triiodothyronine, which are
      inseparable by currently available methods. The separation is achieved on silica
      gel H in a solvent system consisting of methylacetate-2.5% ammonia (w/v) (95:5
      v/v). The complete analysis takes 2 h.

PMID- 9762143
TI  - A rapid, enzymatic assay for the measurement of inorganic pyrophosphate in animal
      tissues.
AB  - A simple, rapid enzymatic assay for the determination of inorganic pyrophosphate
      in tissue and plasma has been developed using the enzyme pyrophosphate--fructose
      6-phosphate 1-phosphotransferase (EC 2.7.1.90) which was purified from extracts
      of Propionibacterium shermanii. The enzyme phosphorylates fructose-6-phosphate to
      produce fructose-1,6-bisphosphate using inorganic pyrophosphate as the phosphate
      donor. The utilization of inorganic pyrophosphate is measured by coupling the
      production of fructose-1,6-bisphosphate with the oxidation of NADH using fructose
      bisphosphate aldolase (EC 4.1.2.13), triosephosphate isomerase (EC 5.3.1.1), and
      glycerol-3-phosphate dehydrogenase (NAD+)(EC 1.1.1.8). The assay is completed in
      less than 5 min and is not affected by any of the components of tissue or plasma
      extracts. The recovery of pyrophosphate added to frozen tissue powder was 97 +/-
      1% (n = 4). In this assay the change in absorbance is linearly related to the
      concentration of inorganic pyrophosphate over the curvette concentration range of
      0.1 microM to 0.1 mM.

PMID- 9762144
TI  - A radioimmunoassay for tetrahydrocortisol.
AB  - A radioimmunoassay for urinary tetrahydrocortisol (THF) is described. Antibodies
      were produced in rabbits against a THF-monohemisuccinate:bovine serum albumin
      conjugate. The radioimmunoassay procedure involves enzymic hydrolysis of the
      urine, extraction with ethyl acetate, radioimmunoassay, and separation of free
      from bound steroid with Somogyi reagents. The antibody showed some cross-reaction
      with tetrahydro substance S (36%) which does not occur in urine in appreciable
      amounts and with tetrahydrocortisone (10%) which does. An analysis of monkey
      urine extracts before and after tlc purification revealed that the THF antibody
      was specific enough to permit assay of urines for THF during stress experiments
      without a purification step. THF values obtained correlated very highly with 17
      hydroxycorticosteroid values on the same urines obtained from monkeys during a
      chair restraint experience (r = 0.97). Also for comparison purposes these same
      urines were assayed for free THF, total cortisol, and free cortisol. The free
      (unconjugated) steroids showed the greatest percentage increase over basal
      levels.

PMID- 9762145
TI  - Colorimetric determination of succinic acid using yeast succinate dehydrogenase.
AB  - An enzymatic method for the rapid determination of succinic acid in biological
      fluids was developed utilizing yeast mitochondria as a source of succinate
      dehydrogenase. The yeast enzyme catalyzes a complete stoichiometric reduction of
      2- (p-iodophenyl)-3-(p-nitrophenyl)-5-tetrazolium chloride to a red formazan. The
      formazan is extracted into ethylacetate and its absorbance measured at 490 nm.
      The method is simple, specific, reproducible, and very sensitive (0.01 to 0.14
      mumol). The yeast enzyme can be stored in liquid nitrogen for periods of at least
      30 days with no significant change in specific activity. In this respect it is
      superior to a variety of succinate dehydrogenase preparations from animal
      tissues. The method was applied to measurement of succinic acid excreted by
      nonproliferating yeast cells metabolizing glucose. Derepressed yeast cells
      secreted several-fold as much succinic acid as repressed cells submitted to
      identical test conditions.

PMID- 9762146
TI  - Preservation of algal and higher plant ribosomal RNA integrity during extraction
      and electrophoretic quantitation.
AB  - Isolation of high molecular weight ribosomal RNA from the wall-less alga
      Olisthodiscus luteus and the angiospermous plant Sauromatum guttatum is
      described. It has been found that a buffer which contains magnesium must be used
      to successfully isolate Olisthodiscus rRNA whereas the isolation of intact
      Sauromatum rRNA requires a buffer system containing a high amount of the chelator
      EDTA. Sauromatum but not Olisthodiscus extracts were contaminated with
      ribonuclease unless the inhibitor diethylpyrocarbonate was used during the
      ribonucleic acid extraction procedure. Nuclease levels were monitored by
      coincubating [3H]-labeled Escherichia coli ribosomal RNA with the experimental
      RNA samples. The effects of detergents on the isolation and quantitation of RNA
      are presented, and methods to avoid loss of highly thermolabile plant ribosomal
      RNA species are discussed.

PMID- 9762147
TI  - A simple method for synthesizing [gamma-32P]nucleoside triphosphates using
      [32P]acetylphosphate and acetate kinase.
AB  - A simple, rapid, and inexpensive method is described for the synthesis of gamma
      32P-labeled ribo- or deoxyribonucleoside triphosphates. The procedure involves
      chemical synthesis of [32P]acetylphosphate and subsequent phosphorylation of
      nucleoside diphosphates using acetate kinase (EC 2.7.2.1) and a final
      purification step. The entire procedure is performed 8 h or less.

PMID- 9762148
TI  - Colorimetric assay of sialic acid by a methyl-3-benzothiazolinone-2-hydrazone
      reactant.
AB  - A colorimetric assay of sialic acid has been developed in which bound sialic acid
      is oxidized by periodic acid so as to quantitatively release formaldehyde. In the
      second step of the reaction formaldehyde reacts with methyl-3-benzothiazolinone-2
      hydrazone, giving a colored compound. This method does not require a prior
      hydrolysis and presents the advantage of great accuracy.

PMID- 9762149
TI  - Isolation of protein subunits by coupling to an insoluble matrix: analysis of
      interactions and application to G-actin.
AB  - A criterion has been devised for the assessment of intermolecular contacts
      between protein subunits coupled to a gel matrix. After reversible coupling by
      way of disulfide groups to Sepharose 4B, the system is exposed to a bifunctional
      reagent. The protein is then released by reduction, and the proportion of dimers
      and higher oligomers formed by cross-linking is determined by gel
      electrophoresis, followed by densitometry of the stained gels. Experiments were
      performed with G-actin coupled to dithio-2-dipyridyl Sepharose 4B. At low
      concentration of coupled protein, no species other than the monomer were
      obtained; under these conditions any intermolecularly cross-linked species would
      represent pre-existing associated states coupled to the matrix. At higher protein
      concentrations dimers and higher species progressively appear. Their proportion
      is much higher than predicted on the basis of a random statistical distribution
      of coupled molecules throughout the accessible internal volume of the matrix. It
      follows that protein-protein contacts can occur either because of high
      flexibility of the polysaccharide chains of the matrix, or because the protein is
      partly (but not wholly) present as a shell on the surface of the beads. With Affi
      gel 10, which has N-hydroxysuccinimide ester coupling groups, similar experiments
      were performed, taking advantage of the degradation of the matrix under
      relatively mild acid conditions. In this case the degree of cross-linking was
      much lower than in the Sepharose 4B system at the same protein concentration.
      However, this medium proved unsatisfactory for the measurement of interactions of
      the bound actin with other muscle proteins present in the mobile phase. The
      results with Sepharose 4B support the validity of previous studies on interaction
      of monomeric actin with other muscle proteins.

PMID- 9762150
TI  - Estrogen determination using liquid chromatography with precolumn fluorescence
      labeling.
AB  - A liquid chromatography procedure is described for the determination of some
      estrogens using fluorescence detection. The estrogens are labeled by precolumn
      derivatization with 5-dimethylaminonaphthalene-1-sulfonylchloride (dansyl
      chloride) and chromatographed on a reversed-phase, C-18 column with a mobile
      phase consisting of methanol, water, and acetic acid. The eluted analytes are
      measured with a fluorescence detector using excitation and emission wavelengths
      of 350 and 540 nm, respectively. The chief advantage of this new procedure is its
      sensitivity, requiring smaller amounts of sample to detect and quantitate
      estrogens in biological materials. We could detect less than 400 pg of estriol.
      With our procedure, this corresponded to about 25 ng in the final reaction
      mixture, before derivatization. The use of smaller sample volumes could improve
      this limit. Linearity for dansylated estriol, estrone, and estradiol was
      excellent over the estrogen range below 100 micrograms in the sample. This
      corresponds to approximately 1.7 micrograms on the column. Within-run precision
      was better than 5% for the full extraction and derivatization procedure for
      estriol from pregnancy urine samples. Chromatography is complete within 10 min
      for dansylated estriol, estrone, and estradiol.

PMID- 9762151
TI  - A rapid method for hemoglobin chain recombination.
AB  - A rapid method for hemoglobin chain recombination which gives a homogeneous
      product was developed. The method utilizes a small carboxymethylcellulose column
      as a medium for chain recombination and concentration of the hemoglobin.
      Equimolar amounts of p-hydroxymercuribenzoate derivatives of alpha- and beta
      chains were mixed with 300 x molar excess of beta-mercaptoethanol over the p
      hydroxymercuribenzoate groups. After 10 min of incubation in an ice bath, the
      mixture was adjusted to pH 5.85, and was loaded on a carboxymethylcellulose
      column. The column was washed with 10 mM phosphate buffer-1 mM Na2EDTA-47 mM beta
      mercaptoethanol, pH 5.85 and then with 10 mM phosphate buffer, pH 5.85. The
      hemoglobin was eluted from the column by use of 15 mM K2HPO4. The hemoglobin was
      homogeneous on polyacrylamide gel electrophoresis and had a visible spectrum,
      electrophoretic mobility, and number of -SH groups comparable to those shown by
      control hemoglobin.

PMID- 9762152
TI  - Interaction of antibody with antigen immobilized on polystyrene latex beads:
      characterization by density gradient centrifugation.
AB  - Isopycnic banding by density gradient centrifugation was used to measure density
      changes in complexes formed by the interaction between antigen and antibody
      immobilized on polystyrene latex beads (diameter, 0.109 +/- 0.0025 micron).
      Measurements of density changes allowed calculation of the interacting masses
      under the given experimental conditions. Interaction equilibrium constants and
      free energy change for two sets of reactions, bovine IgG and anti-bovine IgG
      (rabbit) IgG and rabbit IgG and anti-rabbit IgG (goat) IgG systems, were
      calculated from isopycnic banding density gradient centrifugation runs. The
      procedure demonstrates a new method of obtaining quantitative information on
      antigen-antibody interactions.

PMID- 9762153
TI  - Arylamidation and arylation by the carcinogen N-2-fluorenylacetamide: a sensitive
      and rapid radiochemical assay.
AB  - N-acetoxy-N-arylacetamides, which are generally considered as an ultimate
      carcinogenic form of the corresponding N-arylacetamides, react with the cellular
      macromolecules (nucleic acids, proteins, etc.) to give two types of adducts: (I)
      arylamidation and (II) arylation addition products. In this paper, we present a
      radiochemical determination of the amount of N-2-fluorenylacetamide bound to DNA
      via arylamidation or arylation, respectively. This assay is based upon the
      difference of stability under weak alkali hydrolysis conditions (0.1 N NaOH, 75
      degrees C, 2 h) of the specifically 14C-labeled N-acetyl group of the N-2
      fluorenylacetamide residue linked to the macromolecule either via arylamidation
      or arylation. Native DNA which has been reacted with N-acetoxy-N-2
      [14C]acetylaminofluorene exhibits 16% of the fluorene adducts linked to the bases
      via arylation. On the other hand, denatured DNA reacts with the fluorene
      derivative to give almost only arylamidation addition products.

PMID- 9762154
TI  - A new chromogenic substrate for angiotensin-converting enzyme.
AB  - The compound para-nitrobenzyloxycarbonylglycyl-(S-4-nitrobenzo-2-oxa- 1,3
      diazole)-L-cysteinylglycine [NO2ZGly(S-NBD)CysGly] with an absorption maximum at
      423 nm is readily hydrolyzed by angiotensin-converting enzyme (EC 3.4.15.1.
      peptidlyldipeptide hydrolase) to yield the S-benzfurazan derivative of
      cysteinylglycine. An internal S-->N shift occurs immediately to yield the N
      benzfurazan derivative which in turn reacts with the sulfhydryl reagent 4,4'
      dithiodipyridine to produce the mixed disulfide with an intense absorption at 461
      nm. The maximum difference in molar absorptivity of 13,000 M-1 cm-1 occurs at 470
      nm.

PMID- 9762155
TI  - An artifact produced by boiling adenyl cyclase reaction mixtures prior to the
      cyclic AMP-radioimmunoassay.
AB  - An artifact of procedure has been detected in the adaptation of the cAMP
      radioimmunoassay to the analysis of adenyl cyclase activity. When reaction
      mixtures containing ATP and MgCl2 were boiled to terminate the enzyme assay, a
      cAMP-like decrease in antigen-binding was found. This decrease was dependent upon
      the presence of ATP, was linear to at least 5 min of boiling time, and could be
      destroyed with the addition of commercial phosphodiesterase. As significant
      levels of the nonenzymatically formed product resulted only when samples were
      boiled, alternative methods of terminating cyclase reactions are suggested.

PMID- 9762156
TI  - Molar absorbance of tRNA.
AB  - Examination of some published values suggests that the concentration of most
      tRNAs can be evaluated on the basis of epsilon 260 = 7200/base, in magnesium
      buffer.

PMID- 9762157
TI  - Modification of aspartic acid residues to induce trypsin cleavage.
AB  - 1,2-Diaminoethane and diaminomethane were coupled to aspartic acid residues in
      small peptides by means of a water-soluble carbodiimide. The resulting modified
      side chains sufficiently resembled lysine for trypsin to cleave the peptides.
      Similar modification of glutamic acid residues in peptides gave little or no
      susceptibility to trypsin.

PMID- 9762158
TI  - [Superficial cancer of the stomach at the dawn of the XXI century].

PMID- 9762159
TI  - [Superficial cancer of the stomach in the area of Calvados from 1978 to 1990.
      Epidemiology and prognostic factors].
AB  - AIMS OF THE STUDY: The 5-year survival rate of gastric cancer is less than 20% in
      cancer registries. The prognosis of early gastric cancer is much better but this
      diagnosis is rare in Europe. The aim of the study was to evaluate the prognosis
      and trends in the incidence of early gastric cancer in the area of Calvados
      (France) during a 13-year period. METHODS: Between 1978 and 1990 the Digestive
      Cancer Registry of Calvados recorded 1,160 new cases of gastric cancer. The
      diagnosis of early gastric cancer was defined according to the Japanese
      Gastroenterological Society criteria. Prognostic factors were determined with
      univariate and multivariate analysis. RESULTS: One hundred patients had early
      gastric cancer (8.6%). This rate did not change significantly during the period.
      The mean age was 64.2 +/- 1.5 in males and 64.8 +/- 2.2 in females and 39% of
      patients were older than 70. A precancerous condition was present in 56% of cases
      on the surgical specimen. A total gastrectomy was performed in 23% of cases and a
      subtotal gastrectomy in 72% of cases. The postoperative mortality was 5% and the
      5-year relative survival was 86.8% +/- 4.6. Univariate and multivariate analysis
      found a better prognosis in patients younger than 75 or in patients with a
      superficial or excavated gross appearance compared with those older than 75 or
      with a protruded type. Lymph node metastasis, depth of invasion, size of the
      tumor and histologic differentiation did not influence significantly the outcome.
      CONCLUSION: According to the data of the Cancer Registry of Calvados the
      proportion of Early Gastric Cancer was low and did not change between 1978 and
      1990. The prognosis of EGC is good, mainly altered in elderly and in cases with a
      protruded type.

PMID- 9762160
TI  - [Superficial cancer of the stomach: evolution of their characteristics over a 20
      year period in one population].
AB  - OBJECTIVES: The aim of this study was to analyse the incidence, treatment and
      prognosis of early gastric cancer in a population-based series and to draw a
      picture of time trends. METHODS: Over a 20-year period (1976-1995), 80 early
      gastric cancers were diagnosed in the Cote-d'Or area (493,000 residents).
      Incidence rates were calculated by sex, age groups and 5-year periods. Prognostic
      factors were determined using the Kaplan-Meier method and the Cox model. RESULTS:
      Age-standardized incidence rates were 0.8/100,000 in men and 0.3/100,000 in
      women. Incidence increased slightly over time (NS) and their proportion among
      gastric cancers increased from 3.4% (1976-1980) to 7.9% (1991-1995) (P < 0.01).
      Among these cancers, 25 were intramucosal (31.3%), 55 were submucosal (68.8%) and
      8 had lymph node metastases (10.0%). Overall 21 patients (24.1%) had already been
      treated for a peptic ulcer. The 5-year crude survival rate was 63.1% and the
      corresponding net survival rate was 86.3%. Lymph node metastases, location, sex
      and cancer extension and age were independent prognostic factors. CONCLUSIONS:
      Though it is on the increase, the proportion of early gastric cancers remains low
      among gastric cancers. This study confirms the importance of performing a
      gastroscopy with biopsy upon each bout of ulcer and that the prognosis is lower
      than suggested by hospital based series.

PMID- 9762161
TI  - [Are self-expanding metallic esophageal prostheses an effective treatment for
      malignant stenosis of the esophagus? A prospective study of 32 cases].
AB  - The treatment of esophageal carcinoma is frequently palliative. The aims of this
      prospective study were to evaluate the functional results of covered self
      expanding esophageal metal stents in patients with malignant obstruction of the
      esophagus and to compare two models of stent. PATIENTS AND METHODS: From April
      1994 to August 1996, 32 patients were treated with 35 metal stents (Cook Z Stent
      Wilson Cook: n = 21; Ultraflex Boston Scientific: n = 14). Ten patients had a
      fistula. Previous treatment was effective in 30 patients. Initial score of
      dysphagia was 2.68 +/- 0.7. Initial score of Karnofsky was 60 +/- 10%. The metal
      stents could be placed in 100% of cases. The 30-day mortality was 0%. The
      morbidity of device placement of metal stents was 28%. The treatment of fistulas
      was effective without complication in 100% of cases. At month 3, we observed a
      significant decrease of dysphagia score (0.43 +/- 0.25) and a significant
      increase of Karnofsky score (75 +/- 10%) (P < 0.001). The mean duration of
      hospitalization was 5.4 +/- 1.3 days. During mean follow-up of 18 +/- 3.5 months,
      14 patients (44%) died. Any difference concerning mortality and functional
      results was observed between 2 kinds of metal stents. We only observed a
      significant decrease of retrosternal pain in patients treated with Ultraflex
      prothesis. CONCLUSION: Self-expanding esophageal metal stents are a simple and
      effective palliative treatment of malignant obstruction of the esophagus.
      However, their high cost need other cost-efficacy studies to define their
      indications.

PMID- 9762162
TI  - Plasma cholecystokinin and neurotensin after an ordinary meal in humans. A
      prolonged time study.
AB  - BACKGROUND/AIM: Ingestion of a meal causes the release of cholecystokinin and
      neurotensin into the circulation, but little is known about the duration of this
      release. METHODS: Six healthy volunteers were studied. Blood samples for
      cholecystokinin, neurotensin and gastrin assessment were drawn before and after
      consumption of a typical Italian lunch. Postprandial samples were obtained every
      hour for a total of 10 hours. All peptides were measured using previously
      validated radioimmunoassays. RESULTS: Ingestion of the meal caused a prompt and
      significant increase in plasma levels of all three peptides. Cholecystokinin
      remained elevated for about 7 hours and then tended to return towards basal
      values, whereas the increase of neurotensin persisted for the entire period of
      the study (10 hours). Gastrin remained elevated for about 5 hours and then
      declined. The integrated CCK and gastrin responses during the initial
      postprandial hours were greater than those in the late hours, whereas the
      integrated neurotensin response during the initial hours was lower than that in
      the late hours. CONCLUSIONS: The results indicate that, after an ordinary meal,
      cholecystokinin is released into the circulation for about 7 hours, much longer
      than previously reported (3-4 hours). The release of neurotensin begins soon
      after the meal and persists even longer, for at least 10 hours. Possible
      physiological implications of these findings are discussed.

PMID- 9762164
TI  - [Hepatitic C in a prison environment: is screening necessary?].

PMID- 9762163
TI  - [Randomized therapeutic trials in the treatment of acute pancreatitis: 1986
      1996].

PMID- 9762165
TI  - [Auto-immune cholangiopathies].

PMID- 9762166
TI  - [Liver resection in patients with polycystic liver disease].
AB  - OBJECTIVES: Polycystic liver disease is sometimes responsible for chronic
      symptoms linked to hepatomegaly which can result in acute complications such
      hemorrhage or infection of cysts. The aim of this retrospective study was to
      evaluate the results of partial hepatic resection in patients with symptomatic or
      complicated polycystic liver disease. METHODS: Twelve patients (11 women and one
      man, mean age 49) with diffuse polycystic liver disease were treated by partial
      liver resection (left lateral lobectomy in 7, left hepatectomy in 4, and extended
      right hepatectomy in 1). Four patients had terminal renal failures and three had
      chronic haemodialysis. Median follow-up was 34 months. RESULTS: Ascites occurred
      postoperatively in 10 patients (83%) and was long-lasting (> 2 weeks) in 5; all
      patients with end-stage renal failure had long-lasting ascites. One of them died
      on the 40th postoperative day of ascites infection. Another patient with end
      stage renal failure died two years postoperatively from chronic disabling ascites
      and malnutrition while awaiting kidney transplantation. The 10 other patients
      were markedly improved after partial liver resection, including a marked decrease
      in hepatomegaly, and the disappearance of chronic symptoms and cystic
      complications. This beneficial effect was incomplete in the two surviving
      patients with end-stage renal failure until kidney transplantation was performed.
      CONCLUSION: These results suggest that partial liver resection is a highly
      effective treatment in patients with symptomatic polycystic liver disease,
      preferably before the onset of end-stage renal failure.

PMID- 9762167
TI  - [Infection with hepatitis C virus in a prison environment. A prospective study in
      Loos-lez-Lille, France].
AB  - OBJECTIVES: The aim of this study was to assess the prevalence of hepatitis C
      virus (HCV) markers, and risk factors of contamination in a prison population.
      PATIENTS AND METHODS: Eight hundred and six prisoners were prospectively
      included, at the moment of their imprisonment, between December 1st 1995 and May
      31st 1996. Each prisoner was included in a group "drug abusers" or "non drug
      abusers" based on a clinical examination. Serum anti-HCV antibodies were tested
      in each group. Other risk factors were also analysed (type of drug abuse, share
      of syringes and needles, blood transfusion, haemodialysis, and hemophilia).
      RESULTS: Among the 806 prisoners, 30.3% were anti-HCV positive. Four hundred and
      thirty nine prisoners (54.4%) were placed in the "drug abuser" group and 367
      (45.5%) in the "non drug abuser" group. In the first group, 55.6% were anti-HCV
      positive (80% of the prisoners who were intravenous drug users and 10.8% for the
      others) and 4.2% were anti-HCV positive in the second group. CONCLUSIONS: Half of
      the prisoners entering our center were drug abusers and half were anti-HCV
      antibody positive. HCV infection is a major public health problem in prison.

PMID- 9762168
TI  - [Role of mitochondria in drug-induced hepatotoxicity].

PMID- 9762169
TI  - [Role of sex steroids and their receptors in the pathophysiology of
      hepatocellular carcinoma].

PMID- 9762170
TI  - [Diagnosis of mediastinal neuro-endocrine tumor using endosonography guided
      transesophageal puncture biopsy].
AB  - Histologic diagnosis of tumors of the mediastinum is mandatory for therapeutic
      management. The location and the variety of tumors are responsible for diagnostic
      difficulties. Endosonography guided fine-needle biopsy is an efficient and safe
      procedure for the diagnosis of peridigestive masses. We report the case of a
      patient with a neuroendocrine tumor of the mediastinum revealed by a mass
      syndrome. The diagnosis was performed by endosonography guided needle biopsy.

PMID- 9762172
TI  - [Autoimmune cholangitis successfully treated with corticotherapy. One case].
AB  - Autoimmune cholangitis is a rare cause of chronic liver disease which has
      recently been described and associates the clinical, biological, and histological
      patterns of primary biliary cirrhosis without serum anti-mitochondrial
      antibodies. We report a case of this disease in a 67-year-old female. The patient
      presented with jaundice and marked biological cholestasis associated with
      pulmonary fibrosis and salivary and lacrymal sicca syndrome. Serum anti-smooth
      muscle antibodies were found without anti-mitochondrial antibodies.
      Corticotherapy resulted in rapid improvement of clinical and hepatic
      abnormalities, as well as of pulmonary lesions. The patient was still healthy 18
      months later, with low dose corticotherapy. This report emphasizes the possible
      effectiveness of corticotherapy in autoimmune cholangitis.

PMID- 9762171
TI  - [Benign intraductal papillary-mucinous tumors of the pancreas with a 30-year
      follow-up].
AB  - Intraductal papillary mucinous tumors of the pancreas are rare and characterised
      by a malignant potential. Their natural history is unknown. We report a case of
      intraductal papillary mucinous tumor of the pancreas, that was still benign
      although the first symptom was appeared 30 years before the diagnosis. This case
      report demonstrate the possible slow course of these tumors, for which malignant
      degeneration is unpredictable.

PMID- 9762173
TI  - [Diaphragm of cervical esophagus and autoimmunity].

PMID- 9762174
TI  - [Vitamin C and diarrhea].

PMID- 9762175
TI  - [Clostridium difficile pseudo-membranous colitic secondary to taking diclofenac].

PMID- 9762176
TI  - [Intracystic biochemical and tumor markers in a case of pseudo-papillary and
      solid tumor of the pancreas: pay attention to the interpretation].

PMID- 9762177
TI  - [von Hippel-Lindau presenting as acute pancreatitis secondary to multiple
      pancreatic cysts].

PMID- 9762178
TI  - [Association of dermatomyositis and hepatocellular carcinoma. One case One case].

PMID- 9762179
TI  - [Murderous impulses in two patients with chronic hepatitis C treated with
      interferon alpha].

PMID- 9762180
TI  - [Cibenzoline-induced acute hepatitis].

PMID- 9762181
TI  - [Hemoperitoneum due to spontaneous splenic rupture: a rare complication of
      primary cytomegalovirus infection].

PMID- 9762182
TI  - [Meta-analysis or large randomized trial, that is the question].

PMID- 9762183
TI  - [Hepatotoxicity of antituberculosis drugs: practical implications for
      monitoring].

PMID- 9762184
TI  - [Proposition of a code of ethics in clinical research].

PMID- 9762185
TI  - [Percutaneous cholecystostomy. A study of 30 patients].
AB  - OBJECTIVE AND METHODS: The treatment of acute cholecystitis or angiocholitis is
      often difficult in elderly or very ill patients. The aim of this retrospective
      study was to assess the efficacy and the results of ultrasound guided
      percutaneous cholecystostomy in patients with acute cholecystitis or biliary
      tract obstruction and anesthetic or surgical contraindications. RESULTS: Thirty
      patients (25-93 years, 16 men and 14 women) were included in this study.
      Ultrasound guided percutaneous cholecystostomy was successful on the septic
      syndrome in 27 patients; endoscopic sphincterotomy was performed in 6 patients
      after clinical improvement. A failure of the procedure on sepsis was observed in
      3 patients: cholecystectomy was performed after cardiac improvement in one
      patient, and 2 patients died. Two other patients died of extradigestive diseases.
      No serious complication related to cholecystostomy was observed. CONCLUSION:
      Ultrasound guided percutaneous cholecystostomy is a safe and simple procedure. It
      can be done at bedside and has low morbidity and mortality. It can be considered
      as a definitive treatment, or a temporary one with secondary surgical or
      endoscopic management.

PMID- 9762186
TI  - [Mechanisms of drug resistance in digestive tract cancer].

PMID- 9762187
TI  - [Bile acid transport by the liver].

PMID- 9762188
TI  - [Pancreatic cancer or chronic pancreatitis?].

PMID- 9762189
TI  - [Diagnostic value of serum Ca 19-9 antigen in chronic pancreatitis and pancreatic
      adenocarcinoma].
AB  - OBJECTIVES: The value of serum Ca 19-9 dosage for pancreatic carcinoma diagnosis
      has been studied in heterogeneous series. The effect of the complications of
      chronic pancreatitis and pancreatic carcinoma on serum Ca 19-9 value has not been
      assessed precisely. The aims of this study were to assess: a) the value of Ca 19
      9 to differentiate benign from malignant pancreatic disease; b) the influence of
      complications (particularly, cholestasis). METHODS: The studied population
      included 179 patients: 126 with chronic pancreatitis (25 females, 101 males, 45
      with cholestasis) and 53 with pancreatic carcinoma (27 females, 26 males, 37 with
      cholestasis). RESULTS: At 37 UI/mL threshold, the specificity and sensitivity of
      Ca 19-9 were 53 and 95%, respectively. Cholestasis was associated with a
      significant increase of Ca 19-9 in patients with chronic pancreatitis but not in
      those with pancreatic carcinoma. At 300 UI/mL threshold, the specificity and
      sensitivity of Ca 19-9 were 95 and 81% in patients without cholestasis and 87 and
      81% in those with cholestasis, respectively. Diabetes mellitus was associated
      with a significant increase of Ca 19-9 only in patients with chronic pancreatitis
      without cholestasis. Pancreatic calcifications, pseudocysts, cirrhosis, pleural
      effusion or ascites were not associated with significant variation of Ca 19-9.
      CONCLUSION: In patients with pancreatic disease, 300 UI/mL threshold is the most
      accurate to differentiate benign from malignant disease, whatever the presence of
      cholestasis.

PMID- 9762190
TI  - [6-mercaptopurine levels and study of blood lymphocyte subsets during
      azathioprine treatment of Crohn's disease].
AB  - OBJECTIVES: Our aim was to study the relationships between clinical efficacy of
      azathioprine, 6-mercaptopurine pharmacokinetics and changes in peripheral blood
      lymphocyte subpopulations induced by azathioprine treatment in Crohn's disease.
      METHODS: Twenty-three patients were prospectively followed up for 1 year.
      Peripheral blood counts, total lymphocytes, CD3+, CD4+, CD8+, CD25+, CD16+CD56+,
      CD57+ and CD19+ lymphocyte subpopulations were carried out, using flow cytometry,
      during azathioprine treatment. Pharmacokinetic studies were performed at day 8
      and month 3 by measuring 6-mercaptopurine plasma concentration after an oral dose
      of azathioprine (2 mg/kg). Results were compared in responders (no activity and
      no steroids) and non-responders. RESULTS: The decrease in peripheral blood
      leukocytes and neutrophils was significant after 1 month, reaching 49% and 48% of
      the pre-treatment values at 1 year; the one of lymphocytes was significant after
      6 months and reached 41% at 1 year. Percentages of CD3+, CD4+, CD8+, CD57+,
      CD16+CD56+ and CD19+ lymphocytes remained unchanged whereas percentage of CD25+
      lymphocytes increased from 10% to 28% (P < 0.01). There was a high inter and
      intraindividual variability of 6-mercaptopurine peak plasma concentration and
      area under the curve. No significant difference was found between responders (n =
      14) and non responders (n = 7) for pharmacokinetic parameters and lymphocyte
      subpopulations; there was no correlation between lymphocyte subpopulation changes
      and 6-mercaptopurine pharmacokinetics. CONCLUSION: Monitoring of 6-mercaptopurine
      plasma concentration and blood lymphocyte subpopulations is of little value in
      Crohn's disease patients treated with azathioprine.

PMID- 9762191
TI  - [Prognostic factors in operable epidermoid esophageal cancers].
AB  - OBJECTIVE: The aims of the study were to determine the prognostic factors on
      overall survival in patients with resectable squamous cell esophageal carcinoma.
      POPULATION: Two hundred and ninety three patients with stage I and II tumor were
      included in a phase III clinical trial that compared surgery alone to
      preoperative chemoirradiation. Eighteen parameters issued from clinical,
      biological radiological and pathological characteristics were included in
      univariate and multivariate analysis. RESULTS: The overall survival was
      influenced by: quality of surgical resection tumor response, nodal involvement on
      the CT-scan, tumor length and tumor location. Three groups of patients could be
      identified on two simple clinical preoperative variables. The first group:
      patients without dysphagia with or without nodal involvement on the CT-scan. The
      second group: patients with dysphagia and without nodal involvement on the CT
      scan. The third group: patients with dysphagia and with nodal involvement with CT
      scan. The 5 years survival rates were 34% for the first group, 23% for the second
      group and 0% for the third group. CONCLUSION: The identification of prognostic
      factors is valuable for the stratification of patients in future therapeutic
      studies.

PMID- 9762192
TI  - [Crohn's disease and blood vessels].

PMID- 9762193
TI  - [Consensus conference. Prevention, diagnosis and treatment of colon cancer].

PMID- 9762195
TI  - [Adult idiopathic ductopenia. 1 case].
AB  - Idiopathic adult ductopenia is very rare. We report one case in a 30-year-old
      man, whose clinical course was characterized by jaundice and pruritus. Laboratory
      investigations revealed cholestasis and polyclonal hypergammaglobulinemia. Serum
      antinuclear, antimitochondrial, and anti-smooth muscle antibodies and serological
      markers for viral hepatitis were negative. Endoscopic retrograde cholangiography
      showed no liver or biliary tract abnormalities. Histological examination of a
      liver specimen showed a vanishing bile duct syndrome and moderate portal
      infiltration with lympho-histiocytic cells; there were no granulomas. Liver
      transplantation was performed due to rapid development of cirrhosis. The
      differential diagnosis of idiopathic adult ductopenia with small duct primary
      sclerosing cholangitis, auto-immune cholangiopathy, and non syndromic paucity of
      intrahepatic bile ducts is unclear.

PMID- 9762196
TI  - [Severe hemorrhagic gastritis of radiation origin].
AB  - Severe gastric complications due to radiotherapy are uncommon, in particular
      hemorrhagic gastritis. A high total dose and, above all, high daily fraction
      appear to be the main risk factors in gastric injuries. A case of hemorrhagic
      gastritis induced by radiotherapy requesting a total gastrectomy is reported. The
      patient was treated for a primary gastric non-Hodgkin's lymphoma. Hemorrhagic
      gastritis occurred despite a low total dose (40 Gy) and 2 Gy daily fractions.
      Upper gastrointestinal endoscopy and repeated biopsies are usually insufficient
      to exclude a tumor recurrence. Endoscopic ultrasonography may argue for a
      recurrence or for radiation lesions. As the conservative treatment is usually
      ineffective, these gastrointestinal radiation injuries ought to be treated
      surgically. Besides it allows to ascertain the benign nature of radiation
      lesions.

PMID- 9762197
TI  - [A case of digestive epilepsy with late diagnosis: a disease not to be
      disregarded].
AB  - Digestive epilepsy is a rare disease, poorly recognized by gastroenterologists.
      Its diagnosis requires a compatible clinical presentation, the absence of
      concomitant organic digestive disease, and an effective and long-lasting response
      to specific anticonvulsant agents. We report a case of digestive epilepsy due to
      a meningioma of the right parietal lobe in a 79-year-old woman suffering from
      headaches, vertigo, sweating and abdominal pain for at least 14 years. Initial
      diagnosis was irritable bowel syndrome. A meningal syndrome led to neurological
      work-up showing cerebral meningioma. The recurrent paroxysmal abdominal pain was
      interpreted as manifestations of digestive epilepsy, and effective and long
      lasting treatment was obtained with carbamazepine. After analysis of the
      determining elements in this case, the epidemiology, pathophysiology, diagnostic
      work-up, therapy, and differential diagnosis of digestive epilepsy are discussed.

PMID- 9762198
TI  - [The synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome, a rare
      extra-digestive manifestation of Crohn's disease. Presentation of 1 case and
      review of the literature].
AB  - We report the case of a 33-year-old man with a severe Crohn's disease since the
      age of sixteen. He presented with acne and palmoplantar pustulosis associated
      with a right knee synovitis. Investigations revealed a major axial bone
      condensation. The association synovitis-acne-pustulosis-hyperostosis-osteitis
      leaded to the diagnosis of SAPHO syndrome associated with Crohn's disease.

PMID- 9762199
TI  - [Cost of hemostatic treatment of hemorrhage due to esophageal varices rupture].

PMID- 9762200
TI  - [Acute autochtonus hepatitis E in Lorraine].

PMID- 9762201
TI  - [Hepatocellular carcinoma complicating agenesis of the portal vein].

PMID- 9762202
TI  - [Retrogastric abscess secondary to gastric varices obturation with
      cyanoacrylate].

PMID- 9762203
TI  - [Severity of Hirschsprung's disease in the adult].

PMID- 9762204
TI  - [Pneumopericardium and drug-induced ulcer in an intrathoracic Nissen
      fundoplication].

PMID- 9762205
TI  - [Primary melanoma of the small intestine].

PMID- 9762206
TI  - [Opiod antagonists and treatment of cholestatic pruritus].

PMID- 9762207
TI  - [Proctology teaching: impossible reality? Creation of a Complementary Special
      Study Diploma of Medico-surgical Proctology].

PMID- 9762208
TI  - [What is the role of endo-rectal echography in monitoring of patients operated on
      for rectal cancer?].

PMID- 9762209
TI  - [Adjuvant chemotherapy for colon adenocarcinoma in the county of Cote-d'Or].
AB  - OBJECTIVES: The aim of this study was to assess the use of adjuvant chemotherapy
      in colon adenocarcinomas on a population basis and determine which factors could
      modulate its prescription. METHODS: The influence of time of diagnosis, age, sex,
      place of residence, health care pattern, tumor location and number of metastatic
      lymph nodes was investigated from the 1988 to 1995 data from the Registry of
      Digestive Cancers in Cote-d'Or (France). Each independent variable was given an
      odds-ratio (OR). RESULTS: An adjuvant chemotherapy was performed for 0.9% of 231
      Dukes'A cancers, 3.8% of 367 Dukes'B and 16.7% of 264 Dukes'C. For the latter,
      the prescription of adjuvant chemotherapy was influenced by time of diagnosis
      (from 1.3% in 1988-89 to 35.8% in 1994-95; OR = 228 for period 1994-95 compared
      with the first period), age (the proportion of treated patients under 75 years of
      age has increased from 2.2% in 1988-89 to 57.9% in 1994-95; OR = 30.1 for
      patients younger than 75 years compared with older ones) and health care pattern
      (OR = 0.21 for treatment in non university hospitals and 0.06 in the private
      sector compared with university hospitals. CONCLUSION: In spite of an increasing
      proportion of patients treated by adjuvant chemotherapy for Dukes'C colon
      cancers, this treatment of proved effectiveness has not yet reached its full
      development.

PMID- 9762210
TI  - [Cisplatin, 5-FU and preoperative radiotherapy in esophageal epidermoid cancer.
      Multicenter phase II FFCD 8804 study].
AB  - OBJECTIVES: The aim of this study was to analyze the efficacy and tolerance of
      preoperative radiochemotherapy in esophageal squamous cell carcinoma. Patterns of
      recurrence and prognostic factors were also studied. PATIENTS AND METHODS: This
      multicentric phase II trial included patients deemed operable. Preoperative
      treatment associated 5-FU 800 mg/m2/d by continuous infusion, cisplatin 20
      mg/m2/d and radiotherapy 3 Gy/d D 1-5 and D 22-26. Resection was planned 50 to 60
      days after the beginning of therapy. RESULTS: Seventeen centers accrued 96
      patients, mean age 55.4 years. According to UICC 1978 classification: stage I
      13%, stage II 53% and stage III 30%. Mean follow-up was 73 months. Pre-operative
      treatment was delivered at full dose in half of the patients. Ten percent of the
      patients did not receive the second cycle. Toxicity reached grade 3 in 23% and
      grade 4 in 7% of the patients. Two preoperative deaths occurred. Curative
      resection was performed in 82% of the patients. Operative mortality was 9%.
      tumors were sterilized on the operative specimen in 20% of the patients and
      microscopic remnants were observed in 13%. Preoperative clinical work-up
      overestimated histologic response in 10% of the cases underestimated it in 29%.
      After 2 years, a recurrence was observed in 56% of the patients: loco-regional in
      30%, metastases in 19% and both in 7%. Median survival was 17 months and survival
      rates were 58% at 1 year and 25% at 5 years. Four prognostic factors influenced
      survival in multivariate analysis (Cox model): hematological toxicity grade 3 or
      4, no complete response, circumferential extension > 2/3 and nodes visible on CT
      scan. Factors positively influencing complete response were in multivariate
      analysis: a fungating tumor, weight loss < 8% and a full dose preoperative
      treatment. CONCLUSION: In this study, preoperative treatment associating 5-FU
      cisplatin and radiotherapy allowed a high resectability rate, with one third of
      patients achieving complete or nearly complete histologic response. A randomized
      study is warranted to know whether this combined treatment is better than surgery
      alone.

PMID- 9762211
TI  - [When should patients with bleeding peptic ulcer resume oral intake? A randomized
      controlled study].
AB  - OBJECTIVES: Patients presenting with bleeding peptic ulcers are often kept
      fasted. The contribution of feeding in bleeding recurrence rate is unknown. The
      aim of this prospective controlled study was to evaluate the effect of early
      feeding in (a) the bleeding peptic ulcer recurrence rate and (b) the outcome of
      patients with severe bleeding peptic ulcer. PATIENTS-METHODS: From January
      through December 1995, all consecutive patients admitted for active bleeding from
      peptic ulcer were included. All patients underwent emergency endoscopic injection
      with adrenaline around and into the base of the ulcer and were randomized in two
      groups. Group A patients (n = 12) received milk on day 1, mixed warm feeding on
      day 2 and normal diet from day 3, Group B patients (n = 14) were nil by mouth
      until day 3, then received milk on day 4, mixed warm feeding on day 5, and normal
      diet from day 6. Twenty-six patients (17 men, 9 women, mean age 71 years) were
      included. RESULTS: On day 0, both groups (group A vs group B) were comparable
      (mean +/- SD): hemoglobin (8.8 +/- 2.7 vs 8.1 +/- 2.0 g/dL), transfusion
      requirements in the first 24 h after admission (2.2 +/- 2.0 vs 2.1 +/- 1.4
      units), localization of ulcers (duodenal ulcer: 8 vs 9, gastric ulcer : 4 vs 5).
      There were no significant differences in group A and group B for bleeding ulcer
      recurrence rate (0 vs 1 patient) and transfusion requirements (2.6 +/- 2.1 vs 3.3
      +/- 2.1 units). Hospital stay was significantly shorter in group A (6.8 +/- 2.1
      days) than in group B (9.9 +/- 3.7 days), P = 0.01. CONCLUSION: These results did
      not provide any evidence of advantages of fasting in patients with active
      bleeding peptic ulcer treated by endoscopic sclerotherapy. Early feeding did not
      worsen outcome in patients with active bleeding peptic ulcer and reduced hospital
      stay.

PMID- 9762212
TI  - [Surgical morbidity of segmental colectomy ideally performed via laparotomy for
      complicated colonic diverticulosis].
AB  - OBJECTIVES: The appraisal of morbidity and mortality for one stage elective
      colectomy for complicated diverticulosis is difficult and often overestimated,
      due to the rarity of reports addressing this question. Our results for 100
      patients on a recent 30 month period were studied retrospectively. METHODS: One
      hundred patients were electively operated in a one-stage procedure for
      complicated diverticulosis in a single institution from January 1993 to June
      1995. There were 66 females and 34 males (range: 31-81 years) with a mean age of
      61 years. Main indications for surgery were repeated attacks (34 patients),
      chronic inflammatory mass (26 patients) and stenosis (22 patients). Seventy-eight
      patients had already been admitted for diverticulitis prior to surgery. There
      were 13 surgeons including 6 seniors and 7 fellows. RESULTS: There was no
      mortality. Morbidity was 14% surgical and medical complications accounting for 8%
      and 6% respectively. One patient had an anastomotic fistula treated
      conservatively and another patient was reoperated on for early postoperative
      occlusion There was no perioperative bleeding requiring transfusion. There were
      no surgical trauma of spleen or uretera. Mean hospital stay was 10 days.
      CONCLUSION: This study of a collective surgical experience demonstrates that
      elective one stage left colectomy for benign disease is safe, without mortality
      and with low morbidity.

PMID- 9762214
TI  - [Clinical and Biological Gastroenterology: evaluation of Hepatology division,
      1995 to 1997].

PMID- 9762213
TI  - [Cholesterol crystal embolization in the digestive tract].

PMID- 9762215
TI  - [Antibiotic prophylaxis of ascitic fluid infection].

PMID- 9762217
TI  - [Pro-inflammatory cytokines in the pathogenesis of alcoholic hepatitis].

PMID- 9762216
TI  - [Adult multi-nuclear cell hepatitis. A study in 17 patients].
AB  - OBJECTIVES: Giant-cell hepatitis is rare in adults and its significance has not
      been clarified. We report the clinical and histological characteristics and
      outcome in a group of adult patients with giant-cell hepatitis. METHODS:
      Seventeen patients with giant-cell hepatitis, hospitalized in our unit between
      1976 and 1992, were studied retrospectively. Giant-cell hepatitis was defined as
      at least two hepatocytes with four or more nuclei per cell on liver biopsy.
      Clinical and biochemical parameters, liver histology, and the serological profile
      of HAV, HBV, HCV, HIV, HSV, EBV, CMV, and paramyxovirus were evaluated.
      Paramyxovirus immunochemistry was performed in 6 liver biopsies. RESULTS: There
      were 11 females and 6 males, an average of 48 years old (range: 29-80). Four
      patients had a well-defined etiology: acute hepatitis B infection with a
      favorable outcome in 2 cases, clometacine induced-hepatitis resulting in death
      from liver failure in one case, and chronic hepatitis B and C in one patient with
      AIDS. Among the 13 patients in which the etiology could not be determined,
      histologically defined acute hepatitis was observed in 8 and chronic hepatitis in
      5. Nine patients were treated with immunosuppressive drugs. One patient was lost
      to follow-up. Eight patients responded to treatment, but 5 patients progressed to
      cirrhosis between 5 months and 7 years. Two of the 4 patients with unexplained
      liver disease who did not receive any treatment died of liver failure.
      CONCLUSION: In patient with acute or chronic hepatitis without an identified
      cause (with or without autoimmune abnormalities), the presence of giant-cell
      hepatitis seems to have a similar evolution as active autoimmune hepatitis. The
      poor prognosis of these patients suggests that early immunosuppressive treatment
      is justified.

PMID- 9762218
TI  - [MRI cholangiopancreatography].

PMID- 9762219
TI  - [Abdominal echography (pelvis excluded) as first approach: indications. Working
      Group of the National Accreditation and Health Evaluation Agency].

PMID- 9762220
TI  - [Abdominal emergencies in type IV ehlers-Danlos syndrome].
AB  - Ehlers-Danlos syndrome denotes a group of inherited connective tissue diseases
      comprising nine types. Type IV Ehlers-Danlos syndrome is the most life
      threatening form. It is characterized by a type III collagen deficiency resulting
      in arterial fragility and death from vascular rupture or bowel perforation. This
      disease involves a col 3A1 gene mutation. We report the case of a 44 year-old
      woman with type IV Ehlers-Danlos syndrome. The medical history of our patient
      included bowel necrosis and two vascular ruptures. We indicate data required to
      establish Ehlers-Danlos syndrome diagnosis and guidelines for patient management.

PMID- 9762221
TI  - [Paraneoplastic intestinal pseudo-obstruction revealing small cell lung
      carcinoma: "the anti-Hu syndrome"].
AB  - A 67-year-old woman was admitted for intestinal pseudoobstruction associated with
      peripheral sensitive neuropathy. Jejunal biopsies performed during laparotomy,
      showed axonal degeneration and lympho-plasmocytic infiltration in myenteric
      plexus. High titer of seric anti-Hu antibodies suggested a paraneoplastic
      syndrome. Thoracic CT scan showed mediastinal lymph nodes. Their histological
      examination confirmed the diagnosis of metastatic small-cell lung carcinoma. Her
      condition gradually deteriorated despite supportive parenteral nutrition,
      chemotherapy, steroids and intravenous immunoglobulins. She died 12 months after
      the onset of symptoms.

PMID- 9762222
TI  - [Cap polyposis: a rare syndrome].
AB  - We report a case of inflammatory cap polyposis of the colon, a rare syndrome,
      affecting the rectosigmoid. It was observed in a context of mucous diarrhea.
      Endoscopic and radiological features consisted of elevated and umbilicated
      nodular lesions. Histology revealed polypoid lesions containing elongated crypts
      with superficial abrasions, covered by inflammatory and fibrinoid material.
      Etiopathogenesis of this new syndrome is unknown.

PMID- 9762223
TI  - [Suicidal impulses in patients with chronic viral hepatitis C during or after
      therapy with interferon alpha].
AB  - We report 5 cases of psychiatric side effects in patients treated with alpha
      interferon for chronic viral C hepatitis. The first case includes depression with
      suicidal impulses without a suicide attempt; there was a positive rechallenge of
      interferon. In the second and third cases, depression occurred during interferon
      therapy, but has not disappeared after interferon withdrawal. In the 4th and 5th
      cases, depression occurred after interferon withdrawal. Overall, suicide was
      attempted in 4 cases after interferon withdrawal and was responsible for 2
      deaths. The prevalence of suicide attempts during the 6 to 12 months of
      interferon therapy was 0% compared to 1.3% during the 6 months after interferon
      therapy (P < 0.05) in 306 patients with chronic hepatitis C treated by interferon
      in our local area network during the same period. IN CONCLUSION: a) depression
      does not always disappear after interferon is discontinued; b) regular
      psychiatric follow-up is justified during treatment with interferon; c)
      psychiatric supervision should be continued, even more frequently after
      interferon withdrawal; d) the increased risk of psychiatric side-effect due to
      interferon as well as their severity suggest interferon should be administered
      with caution; e) the role of interferon can only be evaluated in controlled
      studies including the incidence and predictive value of emotional disorders.

PMID- 9762224
TI  - [Probable choroid metastasis of an esophageal adenocarcinoma that regressed with
      chemotherapy].

PMID- 9762225
TI  - [Perineal anaerobic necrotizing cellulite after preoperative radiotherapy for
      rectal cancer].

PMID- 9762226
TI  - [Lymphocytic colitis and ticlopidine].

PMID- 9762227
TI  - [Lymphocytic colitis likely attributable to use of vinburnine (Cervoxan)].

PMID- 9762228
TI  - [Veno-occlusive disease after prolonged treatment with senecionine (Hemoluol)].

PMID- 9762229
TI  - Symptomatic liver injury probably related to sertraline.

PMID- 9762230
TI  - [Colonic cancer: why have a consensus conference in 1998?].

PMID- 9762231
TI  - [Colonic cancer: descriptive epidemiology and high-risk groups].

PMID- 9762232
TI  - [Diet and colorectal carcinogenesis: clues for primary prevention].

PMID- 9762233
TI  - [Do aspirin or nonsteroidal anti-inflammatory drugs decrease the risk of
      colorectal cancer?].

PMID- 9762234
TI  - [Conditions necessary for carrying out a screening program].

PMID- 9762235
TI  - [Colorectal cancer screening. Present status in France].

PMID- 9762236
TI  - [Strategy of screening for patients at high risk of colorectal neoplasm].

PMID- 9762237
TI  - Screening for colorectal cancer with Hemoccult-II in the average risk population.

PMID- 9762238
TI  - [What are the costs of an efficient screening strategy for colonic cancer?].

PMID- 9762239
TI  - [Consequences of legal medicine in incidence of colonic cancer screening].

PMID- 9762240
TI  - [Colonic cancer screening: legal aspects of organization and liability].

PMID- 9762241
TI  - [Colonic cancer: change in circumstances and techniques of diagnosis in France
      between 1990 and 1995].

PMID- 9762242
TI  - [Which explorations are useful for colonic cancer diagnosis?].

PMID- 9762243
TI  - [Pretherapeutic evaluation of colonic cancer].

PMID- 9762244
TI  - [Therapeutic management of colonic cancer in France].

PMID- 9762245
TI  - [What are the modalities of elective surgery for colonic cancer? Which items are
      to be included in the operative report?].

PMID- 9762246
TI  - [Emergency management for colonic cancer].

PMID- 9762247
TI  - [Prognosis of colonic cancer in population based studies].

PMID- 9762248
TI  - [What histo-prognostic factors are useful in making a therapeutic decision in
      colonic cancer?].

PMID- 9762249
TI  - [Recommendations for pathologic reporting of resected colonic neoplasms].

PMID- 9762250
TI  - [Which adjuvant treatments and what are their indications following resection for
      cure in colonic cancer?].

PMID- 9762251
TI  - [Management of malignant polyps].

PMID- 9762253
TI  - [Should a recurrence be searched for in colonic cancer patients resected for
      cure? If so, by what means?].

PMID- 9762252
TI  - [Which endoscopic follow-up for resected colonic cancer?].

PMID- 9762254
TI  - [Colonic cancers with visceral metastasis (synchronous or metachronous): which
      surgical treatment to offer?].

PMID- 9762255
TI  - [Colonic cancers: which surgical treatment should be proposed for extra-colonic
      invasion and locoregional recurrence?].

PMID- 9762256
TI  - [Chemotherapy in locally advanced or metastatic colonic cancer].

PMID- 9762257
TI  - [Diet and nonsteroidal anti-inflammatory drugs: role in prevention of colorectal
      cancer].

PMID- 9762258
TI  - [Is colorectal cancer screening feasible and useful?].

PMID- 9762259
TI  - [Which techniques are useful for diagnosis of colonic cancer and for therapeutic
      choice?].

PMID- 9762260
TI  - [What are the standards of curative surgical treatment of colonic cancer?
      Scheduled and emergency surgical procedures. Prognostic factors helpful for
      therapeutic decision making].

PMID- 9762261
TI  - [What should be done after curative surgery for adenocarcinoma of the colon?].

PMID- 9762262
TI  - [Position of adjuvant and palliative chemotherapy in colonic cancer treatment].

PMID- 9762263
TI  - [Surgical treatment of locally advanced and/or metastatic colonic cancers].

PMID- 9762265
TI  - [Hepatocellular carcinoma in the non-cirrhotic liver: renewed interest].

PMID- 9762266
TI  - [Epidemiology of hepatitis C virus infection in 1,304 HCV positive patients:
      variations according to the origin of transmission and year of diagnosis].
AB  - The evolution of epidemiological data on hepatitis C virus infection is poorly
      documented and thus the impact of screening is difficult to evaluate. AIM: To
      study epidemiological variations based on the origin of transmission and the year
      of diagnosis of hepatitis C virus infection. METHODS: The files of all 1304
      patients seen in the hepatology unit of the Rennes University Hospital were
      analyzed (retrospectively before and prospectively after October 1995) in
      relation to epidemiological features. RESULTS: Despite widespread screening which
      is the source of 60% of the diagnoses, the total number of new cases of hepatitis
      C infection per year has not increased. Compared to patients diagnosed in the
      first years following the discovery of the virus, patients recently identified
      were younger (42 +/- 14 years) and frequently drug addicts (40%).
      Aminotransaminases were normal in 20% of cases. The frequency of cirrhosis has
      declined (17%). There has been a decrease in the proportion of patients who
      undergo liver biopsy (50%) and treatment with interferon (one third of patients).
      CONCLUSIONS: The impact of screening on the number of newly treated patients
      seems to be lower than previously predicted.

PMID- 9762267
TI  - [Apoptosis in normal and diseased liver].

PMID- 9762268
TI  - [Duplex Doppler sonography of splanchnic circulation in man. Clinical and
      physiological importance].

PMID- 9762269
TI  - [Diagnosis of Helicobacter pylori infection is still a timely issue].

PMID- 9762270
TI  - [Comparison of quantifying Helicobacter pylori gastric infection by culture,
      histology and C13 urea breath test].
AB  - OBJECTIVES: In Helicobacter pylori infection, the bacterial burden may play a
      role in the pathogenesis of gastric or duodenal ulcerated lesions. It could also
      influence the results of antimicrobial therapy. No simple test has been validated
      to quantify Helicobacter pylori density. The aim of this study was to determine
      the value of histology and/or 13C-urea breath test to quantify the infection as
      compared with quantitative culture, taken as a reference method. PATIENTS AND
      METHODS: Biopsies samples were taken from the antrum at endoscopy in 72 patients.
      Thirty-seven patients with positive urease test at 20 minutes were enrolled in
      the study. Bacterial density was evaluated from biopsies by quantitative culture
      and semi-quantitative histological examination (score from 0 to 3). The bacterial
      density was evaluated as well by 13C-urea breath test from the proportion of
      13CO2 in exhaled air (delta 13CO2) at 20, 40, and 60 minutes as compared with the
      basal level. RESULTS: The bacterial density, evaluated by quantitative culture
      ranged from 5 CFU to 110,000 CFU per mg of tissue. By histology, a score 1 was
      found in 5 patients, a score 2 in 17, and a score 3 in 15. delta of 13CO2
      measured by 13C-urea breath test ranged from 0.2 to 117.5, from 0.2 to 102, and
      from 0.6 to 66.7 at 20, 40 and 60 minutes respectively. The quantity of bacteria
      measured by culture was not significantly higher for these with a score of 3 as
      compared with those with a pooled score of 1 and 2 (P < 0.05). No significant
      correlation was found between the results of quantitative culture and these of
      breath test. CONCLUSION: In practice, evaluation of bacterial burden by a
      histological score seems only accurate for the most severe density (score 3). The
      13C-urea breath test does not allow a reliable quantitative evaluation.

PMID- 9762271
TI  - [A 1993-1995 epidemiological survey of home parenteral nutrition in approved
      centers for adults in France].
AB  - OBJECTIVES: A 1993-1995 three year epidemiological survey of home parenteral
      nutrition was performed through in France in approved centers for adults.
      METHODS: Data were retrospectively collected each year on a standardized
      questionnaire focussing on indications and short term outcome. RESULTS: All
      centers (n = 14) participated in the study and 524 new adult patients were
      recruited. The overall incidence was unchanged at 3.75 patients/10(6) adults.
      Indications for AIDS rose (8 to 18%) whereas other indications were stable.
      Prevalence increased by 19%: 4.40 adults/10(6) patients at 01.01.1996. At six
      months, the probability to stay on treatment was 19.5% for AIDS and cancer
      indications but 52% for others, whereas death rates were 59% and 9% respectively.
      CONCLUSIONS: For both cancer and AIDS indications, short-term treatment was due
      to a poor prognosis. For other diagnosis, complicated with a short bowel in 51%
      of cases, prognosis was excellent but associated with treatment dependency. The
      latter point focuses on the need for additional treatments in irreversible
      intestinal failure.

PMID- 9762272
TI  - [Use of a medium and long chain triglyceride mixture for parenteral nutrition in
      a university hospital: results of an internal audit].
AB  - OBJECTIVES: The aim of this study was to determine whether a medium and long
      chain triglyceride mixture for parenteral nutrition is used in accordance with
      indications and contraindications in hospital practice. METHODS: Patient data
      recorded in 30 consecutive patients included illness, nutritional status,
      laboratory findings before nutrition as well as indications and contraindications
      for parenteral nutrition. RESULTS: When expressed in g.kg-1.day-1 maximal
      recommended doses of the mixture were exceeded in 32% but there was no excess
      when expressed in g.kg-1.hr-1. Serious hepatic insufficiency was present in 11%
      of the patients, 38% had hypertriglyceridemia and one had serious coagulopathy.
      There were 3 contraindications for the mixture. CONCLUSION: Indications for using
      this emulsion were respected, but there were contraindications in 45% of the
      cases. These contraindications are however questionable as is the daily dosage.
      Because the mixture seems better for use in many cases of parenteral nutrition,
      it would appear best to discuss the prescription case by case.

PMID- 9762273
TI  - [Colonic polyps considered unresectable by endoscopy. Removal by combinations of
      laparoscopy and endoscopy in 65 patients].
AB  - OBJECTIVE: To determine to what extent segmental colectomy could be avoided in
      patients with polyps though to be endoscopically unresectable by using
      combination laparoscopy and endoscopy. METHODS: Sixty-five patients referred for
      colonic polyps though to be unresectably by conventional endoscopy were studied.
      After analysis of the endoscopic findings, endoscopy was performed in a
      medicosurgical unit when possible, otherwise a surgical procedure was performed
      consisting of laparoscopy followed by colonoscopy. Therapeutic strategy depended
      on laparoscopic and endoscopic findings. RESULTS: Segmental colectomy was avoided
      in 44 patients (67.7%). Among them, 20 were treated by simple endoscopic polyp
      removal, 12 by laparoscopy-assisted colonoscopic polypectomy, 9 by laparoscopic
      wedge colonic resection and 3 by colotomy after colonic exteriorization and polyp
      resection. Laparoscopic or laparoscopy-assisted segmental colectomy was performed
      in 16. Segmental colectomy by laparotomy was necessary in 5. No complication
      occurred. CONCLUSION: Segmental colectomy for unresectable colonic polyps could
      be avoided in more than half of the patients using laparoscopy and colonoscopy
      combinations.

PMID- 9762274
TI  - [Microscopic colitis].

PMID- 9762275
TI  - [Serum markers for breast and colorectal cancers. Working group reunited by the
      National Health Agency for Accreditation and Evaluation (NHAAE)].

PMID- 9762276
TI  - [Massive hepatic necrosis secondary to treatment of hepatocellular carcinoma by
      percutaneous alcoholization].
AB  - Fatal complications of percutaneous ethanol injection for the treatment of
      hepatic tumors are rare events. We report a case of massive hepatic necrosis
      after treatment by percutaneous ethanol injection of a 4 cm diameter
      hepatocellular carcinoma, which resulted in the death of the patient. The
      mechanism of this complication was probably an intratumoral aterioportal shunt,
      which allowed ethanol to spread through the blood vessels.

PMID- 9762277
TI  - [Duodenal hematoma, acute pancreatitis, and hemoperitoneum after endoscopic
      hemostasis for duodenal ulcer].
AB  - Therapeutic endoscopy is followed by complications in less than 5% of cases. We
      report a case of an intramural duodenal hematoma after local endoscopic injection
      of 28 mL of adrenaline 1/10,000 for a bleeding duodenal peptic ulcer. This
      hematoma was associated with acute pancreatitis and was revealed by a
      hemoperitoneum.

PMID- 9762278
TI  - [Extension of an acinar cell pancreatic carcinoma with cystic changes invading
      the Wirsung canal].
AB  - We report a case of acinar cell carcinoma of the pancreas with misleading cystic
      changes. A 32-year-old woman presented with symptoms suggesting acute
      pancreatitis on chronic pancreatitis. The abdominal computed tomography and the
      endoscopic retrograde pancreatography demonstrated hypertrophy of the pancreatic
      head associated with global dilatation of main pancreatic duct and secondary
      canals and a 5 cm communicating cyst. A intraductal papillary-mucinous tumor was
      suggested. Microscopic findings showed a poorly differentiated adenocarcinoma.
      Six months later, a liver metastasis was detected. The microscopic appearance was
      different, suggesting acinar cell carcinoma, confirmed by immunohistochemistry.
      Only two other cases of acinar cell carcinoma with cystic component have been
      reported in the literature.

PMID- 9762279
TI  - [Hepatitis C virus reinfection after an intravenous drug injection].

PMID- 9762280
TI  - [Umbilical metastasis of an hepatocellular carcinoma].

PMID- 9762281
TI  - [Diffuse colon linitis secondary to a gastric adenocarcinoma. Detected during
      diarrhea treated with octreotide].

PMID- 9762282
TI  - [Acute anorectal lesions after a hot-water enema].

PMID- 9762283
TI  - [Ticlopidine, diarrhea and lymphocytic colitis].

PMID- 9762284
TI  - [Ano-perineal endometriosis with external sphincter involvement: a rare
      disorder].

PMID- 9762285
TI  - [In which circumstances is push-type video-enteroscopy really useful?].

PMID- 9762286
TI  - [Comparison of push-type endoscopy and barium transit study of the small
      intestine in digestive bleeding and unexplained iron-deficiency anemia].
AB  - OBJECTIVES: A radiological examination of the small bowel is often performed in
      case of gastrointestinal bleeding of obscure origin. More recently, push-type
      enteroscopy has been reported as a valuable tool in this indication. The purpose
      of this study was to compare the diagnosis efficiency of these two procedures.
      METHODS: From February 1994 to February 1996, 40 patients (mean age: 52 years)
      with obscure gastrointestinal bleeding (iron-deficiency anemia without obvious
      cause of blood loss or malabsorption: n = 17; macroscopic gastrointestinal
      bleeding: n = 23) were examined by small bowel follow-through and push-type
      enteroscopy (jejunoscopy n = 19; double way examination n = 21). Each patient had
      negative upper and lower gastrointestinal tract endoscopies prior to small bowel
      examinations. RESULTS: Small bowel follow-through revealed only one lesion
      potentially responsible for blood loss (2.5%), corresponding to a jejunal
      leiomyoma. Push-type enteroscopy detected small bowel lesions potentially
      responsible for blood loss in 6 patients (15%). The lesions were located in the
      jejunum in 5 cases (arteriovenous malformations: n = 3; metastasis: n = 1;
      leiomyoma: n = 1), in the ileum in 1 case (leiomyoma). The efficiency of push
      type enteroscopy for the detection of a small bowel lesion was of 22% in case of
      macroscopic bleeding and of 6% in case of iron-deficiency anemia. Push-type
      enteroscopy also revealed lesions previously undetected by gastroscopy or
      colonoscopy in 8 patients (20%). CONCLUSION: Push-type enteroscopy was more
      effective than small bowel follow-through to detect the origin of obscure
      gastrointestinal bleeding. Push-type enteroscopy revealed a cause of bleeding in
      35% of patients, located in the small bowel in only 15% of the patients.

PMID- 9762287
TI  - [Gene p53 mutations and overexpression of p53 protein in tumors of the Vater's
      ampulla].
AB  - OBJECTIVES AND METHODS: New prognostic markers for tumors of the ampulla of Vater
      which could distinguish aggressive lesions would be highly useful. The aim of
      this study was to evaluate the abnormal expression of p53 protein in a series of
      34 ampullomas with the monoclonal antibody DO7 directed against p53 protein.
      Mutations of exons 5 to 8 of p53 gene were also detected by PCR followed by
      denaturating gel electrophoresis and sequencing. RESULTS: One of 5 adenomas (20%)
      and 16 of 29 adenocarcinomas (55%) were p53 positive by immunohistochemistry. A
      constant feature was the presence of p53 positive glands in the surrounding
      dysplastic mucosa of p53 positive infiltrative lesions. There was no correlation
      between p53 immunostaining and tumor stage. Among the 19 tumors analyzed, 6
      mutations were detected. CONCLUSION: p53 gene mutations and p53 protein
      immunoreactivity are frequently present in ampullomas. Because these alterations
      are not correlated to tumor extension and occur at an early stage in the
      carcinogenesis, their detection does not appear to be contributive for diagnosis
      of ampullary tumors.

PMID- 9762288
TI  - [Therapeutic approach of French practitioners to rectal cancer].
AB  - OBJECTIVES: Improvements in treatment of rectal cancer have enabled a better
      control of locoregional disease. Our objective was to describe the therapeutic
      decisions of different specialists implied through clinical cases and the
      influence of their professional characteristics. METHODS: In spring 1996, a
      questionnaire was mailed to a random sample of 621 French physicians, presenting
      3 clinical cases of rectal cancer at different stages. The present analysis deals
      with a clinical case concerning a 46 year-old man bearing a T3N0 tumor, at 7 cm
      from the anal verge. Statistical analysis (uni and multivariate, by logistic
      regression) was performed with SPSS software. RESULTS: Three hundred fifty two
      exploitable responses were returned (response rate: 57%). Half of the physicians
      chose a pluridisciplinary decision modality. There were differences according to
      the speciality (P < 0.003), to the type of practice (public/private) (P < 10(-4))
      and to the proximity of specialized units (P = 0.03). Therapeutic attitudes
      consisted in a combination of radiotherapy and surgery (RT-SU) for 95% of the
      physicians. The therapeutic choice was in agreement with the French consensus
      conference for 71% of physicians. Two main attitudes emerged for this clinical
      case: exclusive RT-SU combination (43.5%) and RT-SU with optional or systematic
      chemotherapy (CT) (52%). The latter choice appeared to be closely dependent on
      medical speciality (P = 0.0004) and background (P = 0.002). CONCLUSION: Decision
      making is mainly related to the place of work, whereas the therapeutic attitude
      depends on physicians' own characteristics. Until 1990, multiple therapeutic
      options for rectal cancer were performed in France. Nowadays, for a T3N0 tumor,
      the argumentation is rather focused on the indication of CT combined with the
      standard RT-SU treatment. Results from ongoing controlled studies will help
      update consensual recommendations.

PMID- 9762289
TI  - [Intestinal inflammation and motility].

PMID- 9762290
TI  - Predictive factors of variceal bleeding control by emergency sclerotherapy.
      Multicenter Group.
AB  - OBJECTIVES: Acute bleeding from esophageal varices is a major complication of
      cirrhosis. Despite the large number of published studies no predictive factors of
      control of bleeding have been identified. We assessed the clinical and biological
      factors predictive of bleeding control within the first 2 weeks after a bleeding
      episode in a homogeneous group of patients enrolled in a large multicenter trial,
      who underwent a standardized emergency sclerotherapy session. METHODS: 101
      patients with cirrhosis were enrolled. All had endoscopy-proven variceal
      bleeding, and the interval between hematemesis or melena and emergency
      sclerotherapy was always less than 24 hours. A second sclerotherapy session and
      other methods for the prevention of rebleeding were allowed after 5 days.
      RESULTS: Treatment failed in 16 patients after 24 hours and in a total of 33
      patients after 15 days. Three of the 17 variables included in multivariate
      logistic analysis were associated with failure at 24 hours: encephalopathy (P =
      0.006, OR = 4.0), blood transfusion prior to sclerotherapy (P = 0.012, OR = 6.2)
      and previous propranolol therapy (P = 0.022, OR = 4.6). Two variables were
      associated with failure between 24 hours and day 15 in patients successfully
      controlled after 24 hours: an interval between the onset of bleeding and
      sclerotherapy of less than 12 hours (P = 0.010) and blood transfusion (P =
      0.018). After 15 days, three variables were associated with failure in a
      multivariate Cox model: encephalopathy (P = 0.0025, OR = 2.3), time to
      sclerotherapy (P = 0.022, OR 2.3) and blood transfusion before sclerotherapy (P =
      0.0005, OR = 4.0). CONCLUSION: Encephalopathy, the severity of bleeding, assessed
      in terms of transfusion requirements, and the time between clinically overt
      bleeding and sclerotherapy are the main predictive factors of failure of the
      control of bleeding after emergency sclerotherapy for acute bleeding from
      esophageal varices.

PMID- 9762291
TI  - [Autoimmune hepatitis induced by fibrates].
AB  - AIM: Long term treatment by fibrates could induce chronic hepatitis associated
      with auto-antibodies. The aim of this study was to assess the features of this
      hepatitis. METHODS: Baseline clinical and biological features, and liver biopsy
      in 5 patients with fibrate-induced chronic hepatitis were studied, as well as
      their outcome. RESULTS: At enrollment, patients (4 men, mean age 65 years) had
      highly (n = 3) or mildly (n = 2) increased serum aminotransferase activity,
      hypergammaglobulinemia and high titers of anti-nuclear antibodies (with
      homogenous fluorescence in 3 cases). Liver biopsies demonstrated a lympho
      plasmocytic infiltrate in all cases. Hepatocellular necrosis was multilobular in
      2 cases, and mild to moderate, located in lobular and periportal areas in 3
      cases. Cirrhosis was found at presentation in 3 cases and developed within a few
      months in the 2 other patients. After discontinuation of fibrates,
      aminotransferase activity normalized within 6 weeks either spontaneously (n = 3)
      or under immunosuppressive treatment (n = 2). Immunosuppression was rapidly
      withdrawn in 2 patients (< 18 months) without relapse, while one patient was
      treated for 4 years because of relapse after early withdrawal. A second liver
      biopsy performed 6 months after discontinuation of fibrates in an untreated
      patient showed no inflammation or necrosis. CONCLUSION: These observations
      suggest that fibrates could trigger chronic liver disease resembling type I auto
      immune chronic hepatitis, which resolves after drug withdrawal.

PMID- 9762292
TI  - [Polarity of epithelial cells of the liver. Cellular and molecular mechanisms,
      and pathologic changes].

PMID- 9762293
TI  - [Myotomy for esophageal muscular hypertrophy with eosinophil infiltration of the
      esophagus associated with toxocariasis revealed by esophageal motor disorder].
AB  - We report the case of a 61-year-old-man with an eosinophilic esophagitis with
      esophageal motor disorder associated with toxocariasis. He complained of non
      cardiac chest pain and had eosinophilia leading to the detection of Toxocara
      canis infection. Pain persisted despite treatment of toxocariasis. Basal
      manometry was normal but ambulatory 24-hour manometry-pHmetry showed diffuse
      esophageal spasm. Ultrasonography showed a thickening of the esophageal
      musculature in the two inferior thirds of the esophagus. After failure of
      treatment with sodium cromoglycate steroids and esophageal dilatation, calcium
      antagonists were partially effective. A long esophageal myotomy was performed
      permiting the disappearance of symptoms. The histological examination of a side
      myotomy biopsy showed an eosinophilic infiltration of the esophageal muscle
      layer. This observation leads to discuss the possible relation between
      toxocariasis, the esophageal motor disorder and the eosinophilic infiltration of
      the esophageal muscle layer.

PMID- 9762294
TI  - [Dysphagia revealing Crohn's disease].
AB  - Esophageal involvement in Crohn's disease is uncommon. We report here a case with
      pre-eminent esophageal symptoms and numerous tuberculoid granulomas at
      histopathological examination. This is an opportunity to review the differential
      diagnoses and to describe the clinical, endoscopic and histopathological features
      of this localisation.

PMID- 9762295
TI  - [Macroaspartate aminotransferase. Study of 5 cases and review of the literature].
AB  - Aspartate aminotransferase can exist as a macroenzyme, which has a higher
      molecular mass than the corresponding enzyme normally found in serum under
      physiologic or pathological conditions. This macroenzyme is often an
      immunoglobulin complexed-enzyme and induces persistently increased serum
      aspartate aminotransferase activity without any corresponding liver or muscle
      damage. We report 5 patients with isolated and persistent increased serum
      aspartate aminotransferase activity in whom a macroenzyme has been detected. Of
      these 5 cases, four were apparently healthy subjects and the last had chronic
      active hepatitis. Electrophoresis of aspartate aminotransferase isoenzymes of the
      subjects' serum showed an abnormal band migrating between mitochondrial and
      cytosolic aspartate aminotransferase. In 3 cases, the macrocomplex consisted of
      aspartate aminotransferase and immunoglobulin G, as shown by the
      immunoprecipitation method. In the patient with chronic active hepatitis, the
      macroenzyme disappeared after liver transplantation. As macroaspartate
      aminotransferase and others macroenzymes, may persist for months or even years,
      it is important for clinicians to be aware of their existence to avoid
      unnecessary invasive or costly procedures.

PMID- 9762296
TI  - [Role of intravenous erythromycin in the preparation for endoscopy in case of
      upper digestive hemorrhage].

PMID- 9762298
TI  - [Endoscopic treatment of refractory hemorrhagic and ulcerated radiation proctitis
      by a new electrocoagulation technique].

PMID- 9762297
TI  - [Minocycline involvement in two cases of acute pancreatitis].

PMID- 9762299
TI  - [Biliary ileus preceded by hematemesis: role of the tomodensitometry assessment].

PMID- 9762301
TI  - [Alcoholism recurrence after liver transplantation for alcoholic cirrhosis].

PMID- 9762300
TI  - [Bone marrow aplasia complicating viral hepatitis A with significant cholestasis:
      a case report].

PMID- 9762302
TI  - [Predictive value of clinico-biological factors in the diagnosis of lithiasis of
      the common bile duct].

PMID- 9762303
TI  - [Lithiasis of the common bile duct: ultrasonography, computed tomography, and
      magnetic resonance cholangiography. Indications and results].

PMID- 9762304
TI  - [Lithiasis of the common bile duct: endoscopic ultrasonography. Results and
      indications].

PMID- 9762305
TI  - [Endoscopic treatment of lithiasis of the common bile duct. Results and
      indications].

PMID- 9762306
TI  - [Surgical treatment of lithiasis of the common bile duct].

PMID- 9762307
TI  - [Cost-effectiveness of various diagnostic and therapeutic approaches to lithiasis
      of the common bile duct].

PMID- 9762308
TI  - [Assessment of the quality of care and its development in France].

PMID- 9762309
TI  - [Evidence-based medicine. Methodology for the development of medical and
      professional recommendations. Research Group on the Digestive System (GRAD)].

PMID- 9762310
TI  - [Which precautions should be taken in case of hepatitis C? From the statement of
      the question to the dissemination of the response in a consensus conference].

PMID- 9762311
TI  - [Evaluation of professional practices with the medical audit method].

PMID- 9762312
TI  - [Conditions of development of the DBS/DH circular dated April 2, 1996 concerning
      endoscope disinfection procedures in health care sites].

PMID- 9762313
TI  - [Problems encountered with the application of the DGS/DH circular dated April 2,
      1996 (concerning endoscope disinfection procedures) in hepato-gastroenterology
      practice].

PMID- 9762314
TI  - [Introduction to digestive tract pain].

PMID- 9762315
TI  - [Pharmacologic approach to chronic pain. Recent findings].

PMID- 9762316
TI  - [Management of pain in endoscopy: are there "gentle" alternatives to
      anesthesia?].

PMID- 9762317
TI  - [Management of chronic severe digestive tract pain].

PMID- 9762318
TI  - [Visceral sensitivity and digestive functional disorders. Clinical significance
      and therapeutic perspectives].

PMID- 9762319
TI  - [Abdominal pain of metabolic and systemic origin].

PMID- 9762320
TI  - [Surgical treatment of anal incontinence].

PMID- 9762321
TI  - [Therapeutic approaches to rectal prolapse].

PMID- 9762322
TI  - [Treatment of anal fistula].

PMID- 9762323
TI  - [Anal fissure: new physiopathologic and therapeutic concepts].

PMID- 9762324
TI  - [Hemorrhoid disease].

PMID- 9762325
TI  - [Perineal neurologic pain].

PMID- 9762326
TI  - [Liver transplantation in France. Current and future status, seen by the French
      Establishment of Grafts].

PMID- 9762327
TI  - [Influence of apolipoprotein E polymorphism in alcoholic cirrhosis].
AB  - OBJECTIVE: To assess whether the polymorphism of apolipo-protein E was associated
      with the development of alcoholic cirrhosis and could influence the severity of
      liver injury evaluated by the Child-Pugh score. METHOD: We investigated 75
      alcoholic patients with a histological diagnosis of cirrhosis, with negative HBV,
      HCV serology and a control group of 54 subjects. Polymorphism of apolipoprotein E
      was performed using PCR. RESULTS: There was no difference for the allele
      frequency and the genotype in the cirrhotic group and the control group.
      Cirrhotic patients with allele epsilon 2 had higher concentration of albumin (P =
      0.01) and a higher level of apolipoprotein AII (P < 0.05) than those with allele
      epsilon 3. They also had a higher concentration of apolipoprotein AI than
      cirrhotic patients with allele epsilon 3 and epsilon 4 (P = 0.01). There was a
      statistical difference between the three genotype groups for prothrombin time (P
      = 0.01). There was no statistical difference between the three genotype groups
      for Child-Pugh score. CONCLUSIONS: Polymorphism of apolipoprotein E was not
      associated with the development of alcoholic cirrhosis. However patients with
      allele epsilon 2 had better hepatocellular function.

PMID- 9762328
TI  - [Helical CT of the liver. Principles and applications].

PMID- 9762329
TI  - [Homogeneous groups of patients in Crohn's disease: reality or imagination?].

PMID- 9762330
TI  - [Colonic involvement in ileal Crohn's disease].
AB  - OBJECTIVES: To determine the risk and predictive factors for colonic extension in
      patients with ileal Crohn's disease. METHODS: One hundred and fifty patients with
      ileal Crohn's disease and no specific colonic lesions on initial colonoscopy were
      studied retrospectively (median follow-up: 51 months). RESULTS: Twelve patients
      (8%) developed colonic lesions. Ten-year cumulated risks (95% confidence
      interval) for colonic extension were 17.2% (range: 5.8-28.6) in the whole group,
      and 22.4% (range: 8.7-36.1) in the group of 86 patients with repeated
      colonoscopy. Young age at diagnosis was the only factor predicting colonic
      extension. Seven patients with colonic extension required immunosuppressive
      therapy but none underwent surgery. CONCLUSION: Ileal Crohn's disease has a low
      tendency for colonic extension. Colonic extension has no major prognostic
      implications.

PMID- 9762331
TI  - [Comparison of long-term course of perforating and non-perforating Crohn
      disease].
AB  - OBJECTIVES: To evaluate the influence of the indication of the first surgical
      procedure on the prognosis of Crohn's disease. METHODS: We compared
      retrospectively the long-term course of 179 patients operated on for a
      perforating disease and 322 patients operated on for a nonperforating disease.
      Mean follow-up was 11 years and 2 months in the two groups. RESULTS: Forty of 179
      (25%) and 106 of 322 (33%) patients with perforating and nonperforating diseases
      underwent a second intestinal resection, respectively. The patients who had been
      operated on for a perforating disease were significantly more often reoperated on
      for the same indication, and conversely. Patients with perforating diseases
      experienced less second resections (actuarial rates: 37 +/- 11% vs 51 +/- 8% at
      ten years respectively), less post-surgical handicaps (mean index 24.9 vs 27.9),
      and fewer patients required immunosuppressive drugs (25 vs 35%). CONCLUSION: Long
      term prognosis of perforating Crohn's disease does not appear to be more severe
      than that of nonperforating disease.

PMID- 9762332
TI  - [Gastrin-17 and G17-gly induce proliferation of LoVo cells through the CCK
      B/gastrin receptor].
AB  - BACKGROUND AND METHODS: Recent studies suggest that glycine-extended gastrin (G17
      gly) stimulates in vitro proliferation of the pancreatic cell line AR4-2J,
      through selective receptors distinct from the CCK-B/G-receptor mediating the
      effects of amidated gastrin (G17). The aims of our study were to examine the
      effects of G17 and G17-gly on the growth of the colorectal cancer cell line LoVo
      and to determine the receptor involved by using selective receptor-antagonist.
      RESULTS: Both G17 and G17-gly stimulated [3H]-thymidine incorporation in a
      concentration-dependent fashion. Maximal stimulation (153 +/- 18% and 166 +/- 17%
      of control, p < 0.01) was achieved with 10 nM G17 and 100 nM G17-gly,
      respectively. These stimulations were fully prevented by the presence of 10 pM
      YM022, a G/CCK B receptor-antagonist, but unaffected by L364,718, a CCK A
      receptor-antagonist. Basal growth of LoVo cells was inhibited by YM022 and
      stimulated by L364,718. CCK A and G/CCK B receptors mRNA were detected in the
      cells. Gastrin immunoreactivity was detected in the cells (16 pM) and in the
      extracellular medium (4.5 pM). CONCLUSION: Both G17 and G17-gly stimulate LoVo
      cells growth through the activation of a gastrin/CCK B receptor. The evidence for
      secreted gastrin and CCK A and B receptors mRNA may further suggest the existence
      of an autocrine loop involving a stimulatory gastrin/CCK B receptor.

PMID- 9762333
TI  - [Physiology and dysfunction of the upper esophageal sphincter].

PMID- 9762334
TI  - [Central nervous system involvement in hepatitis C virus infection].
AB  - Few well-documented cases of central nervous system involvement in patients with
      hepatitis C virus infection have been reported. We describe three patients (two
      men and one woman) with cerebral involvement (ischemia and/or hemorrhage).
      Hepatitis C virus infection was confirmed in all patients by polymerase chain
      reaction detection of hepatitis C virus RNA. These three cases document the
      occurrence of central nervous system involvement in patients with hepatitis C
      virus infection and mixed cryoglobulinemia. Cerebral involvement may be the
      initial manifestation of hepatitis C virus infection.

PMID- 9762335
TI  - [Epiphysis-metaphysis bone ischemia in hemorrhagic rectocolitis and Crohn's
      disease].
AB  - Aseptic osteonecrosis is a rare extraintestinal manifestation in patients with
      inflammatory bowel disease; its true prevalence is not precisely known. Steroid
      treatment undoubtedly participates in the pathophysiology of avascular
      osteonecrosis, however, other factors like hypercoagulability may be involved.
      Two cases of bilateral osteonecrosis of the knees--the first occurring during the
      course of ulcerative colitis, the second in a patient presenting with Crohn's
      disease--are described. Specific location of the lesions and regression of
      symptoms, as well as the importance of magnetic resonance imaging for early
      recognition of osteonecrosis, are noteworthy.

PMID- 9762336
TI  - [Reversible nephrotic syndrome in Crohn's disease complicated with renal
      amyloidosis].
AB  - A 24-year-old woman suffered from ano-rectal Crohn's disease and nephrotic
      syndrome due to glomerular amyloidosis AA. She received azathioprine and
      colchicine for two years. Both Crohn's disease and nephrotic syndrome resolved.
      However amyloid renal lesions were still present. This course is exceptional, and
      leads to a discussion of the treatment of amyloidosis associated with Crohn's
      disease.

PMID- 9762337
TI  - [Ileocolic linitis in Crohn's disease].
AB  - Intestinal cancer is uncommon in Crohn's disease but the risk of developing such
      a tumor is increased. Linitis plastica of the small bowel or colon is very rare.
      We report a case of ileocolonic linitis plastica which occurred 21 years after an
      ileocecal resection for Crohn's disease. Partial small bowel obstruction in
      relation with stricture of the preanastomotic loop prompted us to suspect disease
      recurrence. The tumor was not diagnosed either on preoperative work-up, or during
      surgery but only on the histological examination of the resected specimen.
      Palliative chemotherapy with 5 FU and folinic acid was performed. The patient was
      asymptomatic after a 17-month follow-up. This observation focuses on the clinical
      signs and course of linitis plastica. It also illustrates the difficulty of tumor
      diagnosis in Crohn's disease. Malignant transformation must be suspected if signs
      of active disease re-occur after a lengthy quiescent period.

PMID- 9762338
TI  - [Risk factors of hepatitis C virus contamination among patients admitted at the
      Emergency Service of the Picardie Hospitals. Role of screening carried out
      according to the recommendations of the General Direction of Health].

PMID- 9762339
TI  - [Hepato-biliary involvement in lambliasis].

PMID- 9762340
TI  - [Esophageal tubular duplication in the adult].

PMID- 9762341
TI  - [Duodenal diaphragm-like stenosis caused by the long-term use of aspirin].

PMID- 9762342
TI  - [A new treatment for hemorrhagic complications associated with severe liver
      disease?].

PMID- 9762343
TI  - Multifactorial mechanisms of drug resistance in tumor cell populations selected
      for resistance to specific chemotherapeutic agents.

PMID- 9762345
TI  - Characterization of PKC isozyme specific functions in cellular signaling.

PMID- 9762344
TI  - Cancer cell heparanase activity associated with invasion and metastasis.

PMID- 9762347
TI  - The role of multiple enzyme activation in metabolic flux control.

PMID- 9762346
TI  - Novel advances in the regulation of signal transduction activity.

PMID- 9762348
TI  - Regulation of mitogen-activated protein kinase cascades in the heart.
AB  - Using primary cultures of neonatal rat ventricular myocytes and isolated adult
      rat hearts as models, we have characterized extensively the regulation of MAPKs
      in the heart. The ERKs are activated primarily by GPCR agonists acting through
      PKC. These agonists can also activate the JNKs although the mechanism is unclear.
      Cellular stresses stimulate strong activation of the JNKs, but also cause some
      stimulation of ERKs. Activation of p38-MAPK has so far only been demonstrated in
      intact adult hearts subjected to stresses and probably leads to activation of
      MAPKAPK2. Both cellular stresses and GPCR agonists induce phosphorylation of c
      Jun, but only the latter causes upregulation of c-Jun protein.

PMID- 9762349
TI  - Regulation of secretory type-II phospholipase A2 and of lysophosphatidic acid
      synthesis.
AB  - Secretory non-pancreatic phospholipase A2 (sPLA2), also called type II-PLA2, is
      produced in large amounts under inflammatory conditions, thus accumulating in
      inflammatory fluids. Since the enzyme is virtually inactive on phospholipids from
      intact cells, we have searched for conditions allowing the action of sPLA2 on
      membrane phospholipids. Based on an in vitro model, our studies suggest that only
      those membranes where the transverse distribution of phospholipids has been
      disturbed offer a convenient surface able to interact with the enzyme, which then
      achieves significant degradation of all glycerophospholipids. This results in the
      accumulation of various lysophospholipids such as lysophosphatidylcholine,
      lysophosphatidylethanolamine and lysophosphatidylserine. However,
      lysophosphatidic acid (LPA) can also be generated under these conditions
      involving accumulation of phosphatidic acid in the cytoplasmic leaflet of the
      membrane, followed by its transfer to the outer monolayer. Since LPA is now
      considered as a novel phospholipid mediator, this pathway deserves further
      studies concerning mainly platelets, the main source of LPA identified so far.

PMID- 9762350
TI  - Exploring the mechanistic aspects of mitomycin antibiotic bioactivation in
      Chinese hamster ovary cells overexpressing NADPH:cytochrome C (P-450) reductase
      and DT-diaphorase.
AB  - We have directly demonstrated the involvement of human NADPH: cytochrome c (P
      450) reductase in the aerobic/hypoxic differential toxicity of mitomycin C and
      porfiromycin in living cells by varying only this enzyme in a transfected cell
      line. In the same manner, we have implicated rat DT-diaphorase in the aerobic and
      hypoxic activation of mitomycin C, but found only a minor role for this enzyme in
      the aerobic activation of porfiromycin. DT-Diaphorase does not cause the
      production of an aerobic/hypoxic differential toxicity by mitomycin C, but rather
      activates this agent through an oxygen insensitive pathway. The evidence suggests
      that DT-diaphorase activates mitomycin C more effectively than porfiromycin, with
      porfiromycin being preferentially activated through a one-electron reductive
      pathway. The therapeutic potential of mitomycin antibiotics in the treatment of
      cancer can be envisioned to be enhanced for those tumors containing elevated
      levels of the bioreductive enzymes. However, cytogenetic heterogeneity within the
      tumor cell population and the various environmental factors which impact on
      bioreductive enzyme function, including pH and oxygen tension, may subvert this
      approach. Moreover, if high tumor levels of a drug activating enzyme reflect high
      levels in the normal tissues of the patient, normal tissue damage may also be
      enhanced with possibly no improvement in the therapeutic ratio. Approaches
      utilizing gene therapy, whereby a specific bioreductive catalyst is introduced
      into the tumor cell population via a targeting vehicle to activate a particular
      prodrug, may be more effective in that not only will the prodrug of choice be
      specifically activated in the tumor, but the source of the catalyst, be it
      bacterial, rodent, or human, will not be important. In fact, in the case of DT
      diaphorase and mitomycin C, the rat form of the enzyme could be advantageous
      because it is more effective in activating mitomycin C than is the human form of
      this enzyme. Assuming targeted gene delivery to malignant cells, a non-host
      enzyme which is more effective at activating mitomycin C than the analogous host
      enzyme might also result in less drug activation in normal tissue and, hence,
      less normal tissue toxicity.

PMID- 9762352
TI  - Post-genomic science: converting primary structure into physiological function.

PMID- 9762351
TI  - Multiple folate enzyme inhibition: mechanism of a novel pyrrolopyrimidine-based
      antifolate LY231514 (MTA).
AB  - Extensive biochemical and pharmacological evidence indicates that LY231514 is a
      novel antifolate antimetabolite. LY231514 is transported into cells mainly
      through the reduced folate carrier system and extensively metabolized to
      polyglutamated forms. The polyglutamates of LY231514 inhibit at least three key
      folate enzymes: TS, DHFR, and GARFT, and to a lesser extent AICARFT and C1
      tetrahydrofolate synthase. The combined effects of the inhibition exerted by
      LY231514 at each target give rise to an unusual end-product reversal pattern at
      the cellular level that is distinct from those of other inhibitors such as
      methotrexate and the quinazoline antifolates. The metabolic effects exerted by
      LY231514 on the folate and nucleotide pools are also quite distinct from those of
      MTX and LY309887. The efficient polyglutamation, longer cellular retention and
      the multiple folate enzyme inhibition mechanism may all have contributed directly
      to the exciting antitumor responses now observed in Phase I and II studies. The
      multitargeted inhibition mechanism of LY231514 is particularly intriguing. This
      new level of mechanistic insight, which has evolved from the study of LY231514,
      challenges the traditional concept and paradigm of antifolate drug discovery and
      development which focused on developing very potent and selective inhibitors of
      single folate enzyme targets, such as DHFR, TS or one of the enzymes along the de
      novo purine biosynthetic pathway. Given the complex nature of folate metabolism
      and the critical role of folates in maintaining the physiological functions of
      living systems, it is completely reasonable to suspect that agents which can
      interfere at multiple sites in the folate pathway may trigger and cause more
      biochemical imbalance in the cellular DNA and RNA synthesis of malignant cells
      than agents that act on a single point (Fig. 5). In conclusion, LY231514 (MTA) is
      a new generation antifolate antimetabolite demonstrating inhibitory activity
      against multiple folate enzymes including TS, DHFR and GARFT. In current phase II
      studies, MTA is broadly active as a single agent and is showing very encouraging
      antitumor activity in multiple solid tumors including colorectal, breast and non
      small cell lung cancers (38-43). The every three week dosing schedule has proven
      to be convenient and easy to administer and the clinical toxicities of LY231514
      seem to be well tolerated. More advanced and extensive clinical trials of
      LY231514 are currently in progress.

PMID- 9762353
TI  - Towards the structure-based design of oligonucleotide therapeutics.

PMID- 9762354
TI  - AH receptor-controlled transcriptional regulation and function of rat and human
      UDP-glucuronosyltransferase isoforms.
AB  - Transcriptional regulation and function of rat and human PAH-inducible UDP
      glucuronosyltransferase (UGT) isoforms have been studied. 1. At least two PAH
      inducible UGT isoforms are expressed in a variety of tissues, the rat isoforms
      UGT1A6 and UGT1A7, and the human isoforms UGT1A6 and UGT1A9. 2. For the rat and
      human UGT1A6 isoforms two modes of tissue- and cell-specific regulation were
      found, PAH-inducible and constitutive expression. 3. Transient transfection
      studies, using human UGT1A6/CAT fusion constructs and colon carcinoma Caco-2
      cells, revealed that PAH induction of human UGT1A6 is mediated by the Ah
      receptor. 4. Cell-expressed UGT isoforms were used to study their function in PAH
      metabolism. Rat UGT1A7 and human UGT1A9 appear to be more efficient than the
      corresponding UGT1A6 isoforms in catalyzing glucuronide formation of PAH phenols
      and diphenols. Several isoforms may act together in the formation of
      benzo(a)pyrene-3.6-diol diglucuronide, the major glucuronide found in rat bile.
      The results suggest complex modes of transcriptional regulation of PAH-inducible
      UGTs. They also suggest a major role of these UGT isoforms in detoxication of
      PAHs.

PMID- 9762355
TI  - Gene expression and regulation of N-acetylglucosaminyltransferases III and V in
      cancer tissues.

PMID- 9762356
TI  - Novel physiological functions of cathepsins B and L on antigen processing and
      osteoclastic bone resorption.
AB  - Lysosomal cathepsin B plays an essential role in the processing of ovalbumin as
      an exogenous antigen to produce the complex between antigenic-peptide and major
      histocompatibility-complex class II. Administration of cathepsin B inhibitors, E
      64, CA-074 and vitamin B6, caused the strong suppression of the Th-2 type immune
      responses. We found that pyridoxal phosphate (PAP), a coenzyme form of vitamin
      B6, inhibits the activities of cathepsin B and L in vitro and vitamin B6
      administration induces the inhibition of the lysosomal cathepsin activities in
      vivo. The production of an antigenic epitope (I323-R339) of ovalbumin by antigen
      presenting cells was suppressed by cathepsin B specific inhibitors. The ovalbumin
      dependent production of immunoglobulins (IgE and IgG1) and of the corresponding
      interleukin (IL-4) was suppressed by cathepsin B inhibitors, while the production
      of IgG2a and interferon (INF-gamma) was increased. The switch of helper T
      lymphocyte functions from the type-2 to the type-1 may be induced by the
      cathepsin B inhibition. The experimental bone pit formation, i.e., osteoclastic
      bone collagen degradation test, induced by parathyroid hormone was markedly
      suppressed by the administration of pyridoxal, because of the inhibition of
      cathepsin L type cysteine proteases in bone.

PMID- 9762357
TI  - A role for the amino terminus of human topoisomerase I.
AB  - These studies indicate that SV40T antigen binds the amino terminus of human top1
      both in vitro and in vivo. Additional in vitro data suggest that the interaction
      between these two proteins does not require DNA as an intermediary. Taken
      together with the finding that the amino terminus of top 1 binds the putative
      helicase nucleolin, these results implicate helicase binding as a general
      function of the amino terminus of human top1. Binding of top1 by helicases may be
      important in the management of structural alterations in DNA produced by
      helicases. The potential importance of helicase-topoisomerase interactions has
      been highlighted by recent data indicating that the protein defective in Bloom's
      syndrome is a helicase with a yeast homologue that is known to bind
      topoisomerases.

PMID- 9762358
TI  - Regulation of apoptosis in Xenopus egg extracts.

PMID- 9762359
TI  - Vasculature and microenvironmental gradients: the missing links in novel
      approaches to cancer therapy?
AB  - This paper illustrates how the concept of the malignant cell per se as the prime
      and only target in cancer therapy may be erroneous. The micro-vasculature evoked
      to satisfy nutritional requirements of solid tumors, and the inadequacy of this
      nutrition for all tumor cells, provide novel targeting concepts. The vascular
      architecture and the microenvironmental gradients (VAMP) will differ from one
      tumor to another and may determine whether current therapies succeed or fail.
      Many agents have a different toxicity or mode of action at the pathophysiological
      oxygen tensions that prevail in solid tumors. This warrants more attention. The
      hypoxic cell or the immature proliferating endothelial cell may provide tumor
      specificity that is more general than, and greater than, that conferred by the
      process of malignant transformation. The poor vasculature of solid tumors is
      often regarded as a problem by the oncologist. It limits the access of cytotoxic
      drugs, monoclonal antibodies, cytokines, etc. It also leads to hypoxic
      radioresistance because of diffusion limited chronic hypoxia and perfusion
      limited intermittent hypoxia, resulting from transient vessel closure. However,
      it can also be seen as a potential target, since prolonged vessel occlusion can
      lead to an avalanche of cell death. Strategies to prevent further expansion of
      the vascular network (anti-angiogenesis) should stabilize tumors and prevent
      further growth. Vascular targeting, aiming to damage the microvascular function
      and cause occlusion, can lead to extensive cell death. The target may relate to
      the excessive proliferation of endothelial cells in tumors or to abnormal
      functional aspects, such as altered cell shape (influencing permeability)
      adhesiveness to leukocytes or steps in the coagulation cascade. These
      microvascular features and microenvironmental gradients, and the phenotypic
      consequences of them, have been relatively neglected. The altered milieu and
      inadequate neovasculature is a common feature of all types of solid tumor,
      whereas the genetic changes that can give rise to a malignancy are very variable,
      from tumor site to site and even within a site from individual to individual. It
      seems, therefore, that therapies that could be of widespread general
      applicability might more easily be found from the micro-environmental or anti
      vascular approaches than from gene therapy targeted at specific oncogenes. This
      approach will require cross fertilisation between scientists from quite disparate
      backgrounds, whose paths seldom cross, and who may not read, or even scan, each
      other's literature. If the endothelium or the low oxygen tension in subsets of
      tumor cells are the key to successful cancer treatment in mice, there are
      considerable implications for screening methods in vitro and for predictive and
      prognostic tests made on homogenized tumor samples.

PMID- 9762360
TI  - The physiological role of glucokinase binding and translocation in hepatocytes.
AB  - The compartmentation of glucokinase in the hepatocyte is regulated by the
      extracellular glucose concentration and by substrates that alter the
      concentration of fructose 1-phosphate in the hepatocyte. At low glucose
      concentrations, that mimic the fasted state, glucokinase is sequestered in an
      inactive state bound to the 68 kDa regulatory protein in the nucleus. In these
      conditions the rate of glucose phosphorylation is less than 15% of the total
      glucokinase activity. An increase in extracellular glucose concentration, within
      the range occurring in the portal vein in the absorptive state, or low
      concentrations of fructose or sorbitol (precursors of fructose 1-phosphate),
      cause the translocation of glucokinase from the nucleus to the cytoplasm and this
      is associated with a corresponding increase in glucose phosphorylation. The
      effect of glucose on translocation is mimicked by mannose which is also
      phosphorylated by glucokinase as well as by competitive inhibitors of glucokinase
      (mannoheptulose and 5-thioglucose) which are not phosphorylated. Various lines of
      evidence suggest that the action of these analogues is most likely due to binding
      to an allosteric or non-catalytic site. The saturation curve of glucose
      phosphorylation in intact hepatocytes is sigmoidal with an S0.5 of approximately
      20 mM and a Hill coefficient approximately 2. This saturation curve can be
      explained by the activity of glucokinase in the cytoplasmic compartment.
      Translocation of glucokinase from the nucleus to the cytoplasm in response to
      precursors of fructose 1-phosphate (which cause dissociation of glucokinase from
      the regulatory protein) is associated with stimulation of glucose
      phosphorylation, glycolysis and glycogen synthesis. Using Metabolic Control
      Analysis to determine the Control Coefficient (Control Strength) of cytoplasmic
      (free) glucokinase on glucose metabolism it can be shown that the free
      glucokinase activity has a very high control strength on glycogen synthesis
      (CFGKJ > 1), indicating a major role of translocation of glucokinase in the
      control of hepatic glycogen synthesis. Overexpression of glucokinase in
      hepatocytes by adenovirus-mediated glucokinase overexpression is associated with
      a marked increase in glycogen synthesis. The relation between glycogen synthesis
      and enzyme overexpression is sigmoidal with an enzyme concentration causing half
      saturation (S0.5) in the physiological range. The high Control Coefficient of
      glucokinase on hepatic glycogen synthesis explains the abnormalities of hepatic
      glycogen synthesis in patients with a single mutant allele of the glucokinase
      gene (Maturity Onset Diabetes of the Young, type 2).

PMID- 9762361
TI  - Tumor necrosis factor-alpha mediated activation of signal transduction cascades
      and transcription factors in 3T3-L1 adipocytes.
AB  - We have previously demonstrated that exposure of fully differentiated 3T3-L1
      adipocytes to TNF results in an activation of at least two separate signal
      transduction pathways: 1. the sphingomyelinase leading to generation of ceramide
      and 2. the proliferative and cell growth regulating p44/42 MAP kinase cascade. In
      the current study we extend those observations and examine the ability of both
      TNF and ceramide to activate the stress/cytokine activated p38 MAPK, the JNK and
      JAK-STAT pathways. Interestingly, the p38 MAP kinase was observed to be
      constitutively active and its phosphorylation status (activation) was not altered
      with either TNF or ceramide treatment. Analysis of the JNK and JAK-STAT pathways
      also demonstrated an absence of TNF-induced activation. Similar results were
      obtained when the adipocytes were treated with a cell permeable analog of
      ceramide. However, the adipocytes were observed to respond to TNF with a rapid
      alteration in the GSH-GSSG equilibrium in a manner consistent with a cellular
      response to an oxidative stress. This response may mediate the TNF-induced
      metabolic disturbances observed in the adipose cell.

PMID- 9762362
TI  - Inositides in the nucleus: taking stock of PLC beta 1.
AB  - The nucleus was shown to be a site for inositol lipid cycle which can be affected
      by treatment of quiescent cells with growth factors such as IGF-I. In fact, the
      exposure of Swiss 3T3 cells to IGF-I results in a rapid and transient increase in
      nuclear PLC beta 1 activity. In addition, several other reports have shown the
      involvement of PLC beta 1 in nuclear signalling in different cell types. Indeed,
      PLC beta 1 differs from the PLC gamma and della isozymes in that it has a long
      COOH-terminal sequence which contains a cluster of lysine residues that are
      critical for association with the nucleus. Although the demonstration of PtInsP
      and PtdInsP2 hydrolysis by nuclear PLC beta 1 established the existence of
      nuclear PLC signalling, the significance of this autonomous pathway in the
      nucleus has yet to be thoroughly clarified. By inducing both the inhibition of
      PLC beta 1 expression by antisense RNA and its overexpression we show that this
      nuclear PLC is essential for the onset of DNA synthesis following IGF-I
      stimulation of quiescent Swiss 3T3 cells. Moreover, using a different cell
      system, i.e. Friend erythroleukemia cells induced to differentiate towards
      erythrocytes, it has been evidenced that there is a relationship between the
      expression and activity of nuclear PLC beta 1 and the association of PI-PT alpha
      with the nucleus in that, when PLC activity ceases, in differentiated and resting
      cells at the same time there is a dramatic decrease of the association of PI-PT
      alpha with the nucleus.

PMID- 9762363
TI  - Nuclear inositol signaling: a structural and functional approach.

PMID- 9762364
TI  - Cobalamin-dependent methionine synthase and serine hydroxymethyltransferase:
      targets for chemotherapeutic intervention?
AB  - Chemotherapeutic drugs targeted at folate-dependent reactions have typically been
      directed at a limited number of target enzymes: dihydrofolate reductase,
      thymidylate synthase, and GAR and AICAR transformylase. This review discusses two
      other potential targets for chemotherapeutic inhibition: cobalamin-dependent
      methionine synthase and serine hydroxymethyltransferase. Brief reviews of the
      catalytic properties of these two enzymes are presented, and possible strategies
      for chemotherapeutic intervention are discussed.

PMID- 9762365
TI  - Comparison of proliferating cell nuclear antigen expression in odontogenic
      keratocyst and ameloblastoma: an immunohistochemical study.
AB  - Proliferating cell nuclear antigen (PCNA) is a nuclear protein synthesized in the
      late G1 and S phase of the cell cycle, and immunohistochemical detection of the
      protein represents a useful marker for the proliferating fraction of cells in
      tissue specimens. PCNA expression was studied in odontogenic keratocysts (n = 15)
      and ameloblastomas (n = 46) using an avidin-biotin-peroxidase complex method on
      routinely processed paraffin sections. The percentage of PCNA-positive cells
      determined by point counting was significantly lower in the ameloblastomas (mean
      9.4%, standard deviation (SD) 11.0) than in odontogenic keratocysts (mean 29.9%,
      SD 24.0). In ameloblastomas, the mean percentage of PCNA-positive cells was
      lowest in the acanthomatous pattern and highest in plexiform pattern. The mean
      percentage of PCNA-positive cells in plexiform pattern was non-significantly
      higher than that in follicular pattern. The mean percentage of PCNA-positive
      cells in plexiform and follicular patterns was significantly higher than that in
      cystic and acanthomatous patterns. The frequency of PCNA-positive cells was
      significantly higher in the peripheral cells of follicular and plexiform patterns
      than in the central cells of both patterns (p < 0.01). Therefore, peripheral
      cells were regarded as reserve cell of central cells. The mean percentage of PCNA
      positive cells in the epithelial lining of odontogenic keratocyst was not
      significantly different from those in the peripheral cells of follicular and
      plexiform patterns of ameloblastoma. In contrast, the odontogenic keratocyst
      exhibited a mean percentage of PCNA-positive cells which was statistically higher
      than that in other histological elements of ameloblastomas. The present study
      suggests that odontogenic keratocyst is regarded as benign odontogenic tumour.

PMID- 9762366
TI  - Nuclear and nucleolar image analysis of human breast epithelial cells transformed
      by benzo[a]pyrene and transfected with the c-Ha-ras oncogene.
AB  - Changes in nuclear and nucleolar morphometric parameters were investigated by
      image analysis procedures in human breast MCF-10F epithelial cells expressing
      different stages of the tumourigenic progression after benzo[a]pyrene (BP)
      transformation (BP1, BP1-E, and BP1-E1 cell lines), and additionally transfected
      with the c-Ha-ras oncogene (BP1-Tras cell line). Nuclear pleomorphism was evident
      in all the transformed cells. The analysis of different morphometric parameters
      did not show a clear relationship between specific nuclear and nucleolar changes
      and the expression of the different stages of the tumourigenesis, with the
      exception of the nucleolar size, which could be associated to the expression of
      the tumourigenic phenotype, and a nucleolar area/nuclear area ratio, which
      discriminated the immortalized, the transformed, and the tumourigenic phenotypes
      from one another. The nuclear morphometric data established for the BP
      transformed cells and for the cells additionally transfected with the c-Ha-ras
      oncogene were suggestive of complex and distinct morphofunctional mechanisms
      involving the in vitro transformation of the MCF-10F cells. The nuclear changes
      found in the BP1-Tras cell line were assumed to be related to the additional
      effects and/or enhanced genomic instability induced by transfection with the ras
      oncogene.

PMID- 9762367
TI  - Detection of c-erbB-2 mRNAs using dig-labelled oligonucleotide probe with in situ
      hybridisation in human breast carcinoma: comparison with immunohistochemical
      results.
AB  - Amplification and overexpression of the c-erbB-2 oncogene are of prognostic
      significance in human breast cancer. Overexpression of c-erbB-2 is the result of
      gene amplification. However, increased transcript levels of c-erbB-2 are also
      detected in the absence of gene amplification. In this study for the detection of
      the overexpression mRNA in situ hybridisation (ISH) and immunohistochemistry
      (IHC) were used. Our aim was to develop the suitable mRNA ISH protocol for
      formalin-fixed paraffin-embedded material and to compare the localisation of
      transcripts and protein products in 20 primary breast carcinomas. Sections were
      immunostained with monoclonal c-erbB-2 antibody. In ISH method digoxigenin
      labelled oligoprobe was used for the detection of c-erbB-2 mRNAs. We determined
      optimal condition for the ISH procedure (e.g., probe concentration, digestion,
      post washing). c-erbB-2 protein overproduction was detected in 11/20 cases with
      IHC. The mRNA signals were observed in malignant cell cytoplasm in 6/20 cases by
      ISH. ISH positive signals were found in only one case without detected
      overexpression of the protein. There were cell to cell variations in the
      hybridisation signals even within individual tumours. The ISH and IHC positive
      signals for c-erbB-2 was observed mostly in infiltrating ductal carcinomas that
      belong to aggressive lesions.

PMID- 9762368
TI  - Fast-FISH detection and semi-automated image analysis of numerical chromosome
      aberrations in hematological malignancies.
AB  - A new fluorescence in situ hybridization (FISH) technique called Fast-FISH in
      combination with semi-automated image analysis was applied to detect numerical
      aberrations of chromosomes 8 and 12 in interphase nuclei of peripheral blood
      lymphocytes and bone marrow cells from patients with acute myelogenous leukemia
      (AML) and chronic lymphocytic leukemia (CLL). Commercially available alpha
      satellite DNA probes specific for the centromere regions of chromosome 8 and
      chromosome 12, respectively, were used. After application of the Fast-FISH
      protocol, and microscopic images of the fluorescence-labelled cell nuclei were
      recorded by the true color CCD camera Kappa CF 15 MC and evaluated quantitatively
      by computer analysis on a PC. These results were compared to results obtained
      from the same type of specimens using the same analysis system but with a
      standard FISH protocol. In addition, automated spot counting after both FISH
      techniques was compared to visual spot counting after standard FISH. A total
      number of about 3,000 cell nuclei was evaluated. For quantitative brightness
      parameters, a good correlation between standard FISH labelling and Fast-FISH was
      found. Automated spot counting after Fast-FISH coincided within a few percent to
      automated and visual spot counting after standard FISH. The examples shown
      indicate the reliability and reproducibility of Fast-FISH and its potential for
      automatized interphase cell diagnostics of numerical chromosome aberrations.
      Since the Fast-FISH technique requires a hybridization time as low as 1/20 of
      established standard FISH techniques, omitting most of the time consuming working
      steps in the protocol, it may contribute considerably to clinical diagnostics.
      This may especially be interesting in cases where an accurate result is required
      within a few hours.

PMID- 9762369
TI  - DNA aneuploidy by flow cytometry is an independent prognostic factor in gastric
      cancer.
AB  - In the present study the prognostic value of both DNA ploidy and the
      proliferative activity of tumour cells were studied in a series of 76 consecutive
      patients suffering from gastric tumours. DNA ploidy and the proliferative index
      (as measured by the percentage of S-phase cells) were determined by flow
      cytometry using fresh tumour specimens. The presence of DNA aneuploid clones by
      flow cytometry was detected in 62% of the cases (mean DNA index of 1.63 +/- 0.46;
      range 1.08-2.92), the mean proportion of S-phase cells being of 18.4 +/- 11.5%.
      In comparison with diploid cases, aneuploid tumours showed a higher proliferative
      activity (cases with more than 15% S-phase cells: 18.4% versus 6.1%, p = 0.0001)
      as well as a higher incidence of node involvement (95% versus 68%, p = 0.001). By
      contrast, no significant differences were detected with respect to sex, age,
      histologic grade and type, clinical stage, tumour size and the incidence of
      extranodal involvement. Upon grouping the patients according to the proportion of
      S-phase cells no significant differences were observed for the clinical and
      biological parameters explored except for an association between a high
      percentage of S-phase cells and the presence of DNA aneuploidy (40% versus 96%, p
      = 0.0001). Regarding survival the presence of DNA aneuploidy was significantly
      associated with poor outcome as compared to the diploid cases (median of 15
      versus 26 months, p = 0.005). By contrast, the proportion of S-phase cells did
      not predict patients's outcome. Multivariate analysis of prognostic factors
      showed that the presence of DNA aneuploidy (p = 0.003) together with the
      histologic type (p = 0.03) and the existence of extranodal metastases (p = 0.05)
      were the best combination of prognostic factors for survival prediction.

PMID- 9762370
TI  - Cell proliferation activity and prognostic index in squamous cell lung carcinoma.
AB  - Flow Cytometry (FC) has been incorporated into cancer research in relation to its
      prognostic value together with histological parameters and TNM stages. We have
      studied by means of FC the cell cycle of 132 samples from male patients with
      Squamous Cell Lung Carcinoma (SQCLC). All of the patients received curative
      surgery and the clinical follow-up was 60 months. The clinical and cytometric
      parameters were evaluated in order to predict the patients' outcome. The presence
      of tumoural recurrence and the tumoural stage showed statistical significance
      associated with survival. The multivariant analysis reveals radiotherapy (p =
      0.004) as protective variable and the high S-phase fraction (SPF) (p = 0.001) and
      stage IIIA (p = 0.012) as risk factors. The SPF appears as an independent
      prognostic factor for overall survival time. We can build a prognostic index
      representative of different prognostic groups, which allows us to improve the
      individual monitoring of these patients.

PMID- 9762371
TI  - Stress ulcer prophylaxis in medical ICU patients: annual utilization in relation
      to the incidence of endoscopically proven stress ulceration.
AB  - OBJECTIVE: To measure changes in the proportion of medical intensive care unit
      (MICU) patients prescribed pharmacologic stress ulcer prophylaxis therapy over a
      4-year period in relation to the incidence of stress-related ulceration detected
      by endoscopy at our institution. DESIGN: Retrospective 4-year review of pharmacy
      and endoscopy databases. SETTING: A 35-bed MICU. PATIENTS: Patients (n = 2941)
      admitted to the MICU for longer than 24 hours, between January 1, 1993, and
      December 31, 1996, without acute gastrointestinal hemorrhage on admission.
      METHODS: Records were reviewed to identify patients prescribed pharmacologic
      stress ulcer prophylaxis (> 24 h of sucralfate or a histamine2-receptor
      antagonist [H2RA]), and patients with evidence of stress ulceration during
      endoscopy. RESULTS: The number of patients per year receiving stress ulcer
      prophylaxis significantly (p < 0.001) decreased between 1993 and 1996: 1993,
      492/693 (71%); 1994, 478/798 (60%); 1995, 295/670 (44%); 1996, 164/780 (21%).
      There was no difference between years in the median duration of stress ulcer
      prophylaxis therapy or the proportion of patients receiving sucralfate versus
      H2RA therapy. There was no difference (p = 0.91) between years in the annual
      incidence of definite or possible stress-related ulceration: 1993, 6/693 (0.87%);
      1994, 5/798 (0.63%); 1995, 6/670 (0.90%); 1996, 5/780 (0.64%). CONCLUSIONS: The
      incidence of endoscopically proven stress-related ulceration has remained
      unchanged over the past 4 years in our MICU despite significantly fewer patients
      receiving pharmacologic stress ulcer prophylaxis therapy.

PMID- 9762372
TI  - Effect of a dual-lumen peripheral catheter on the delivery of known incompatible
      medications.
AB  - OBJECTIVE: To determine the degree to which a dual-lumen peripheral catheter
      prevented precipitation of solutions known to be incompatible due to pH during
      simultaneous infusion in an in vitro model. METHODS: An in vitro model was
      devised to simulate peripheral venous blood flow from an antecubital source to
      systemic circulation. Ondansetron was simultaneously infused with fluorouracil,
      aminophylline, sodium bicarbonate, and ampicillin sodium in concentrations
      reflective of clinical conditions into the Twin Cath 20/22 (the dual-lumen
      catheter used in this experiment). Study solutions were primed with the prepared
      drug solution and administered for 15 minutes. Phase I used Normosol-R as the
      diluent to gather preliminary data; phase II used human plasma. All samples were
      obtained immediately before the start of the infusion and at 5, 10, and 15
      minutes during the infusion, and 5 minutes after the infusion. Samples were
      visually inspected at each time point for precipitation and analyzed in duplicate
      by the appropriate stability-indicating HPLC method (except for sodium
      bicarbonate). Compatibility was defined as no visual evidence of precipitation
      and no more than 15% mean change in final versus initial concentration. RESULTS:
      Phase I experiments showed immediate precipitation in Normosol-R within the
      venous flow. However, in phase II, because of the buffering capacity that plasma
      proteins add to plasma, no precipitation occurred. All the drug combinations used
      in this study have been reported to be incompatible at the concentrations tested;
      however, we detected no incompatibilities. CONCLUSIONS: The results of this study
      indicate that using a dual-lumen peripheral catheter, such as the Twin Cath, may
      allow solutions incompatible due to pH to be administered simultaneously.

PMID- 9762373
TI  - Pharmacoeconomic analysis of using Sinemet CR over standard Sinemet in
      parkinsonian patients with motor fluctuations.
AB  - OBJECTIVE: To compare the costs of pharmacotherapy in patients with Parkinson's
      disease before and after converting from standard Sinemet to extended-release
      Sinemet CR. DESIGN: Investigators retrospectively reviewed records of patients
      converting from Sinemet to Sinemet CR for efficacy and total drug costs. Cost
      effectiveness was evaluated retrospectively from data collected in prospective
      Sinemet CR efficacy trials. SETTING: Parkinson's disease clinic at a tertiary
      care university teaching hospital. PATIENTS: 100 patients with motor fluctuations
      who had undergone an initial 6-month course of Sinemet therapy, followed by a 6
      month course of Sinemet CR. MAIN OUTCOME MEASURES: Total cost was measured as the
      cost of Sinemet formulations plus the costs of other antiparkinson medications.
      Differences in pre- and postconversion costs were compared by using the paired,
      two-tailed Student's t-test. A substudy of 39 patients on the cost-effectiveness
      of conversion measured the ratio of daily medication costs to the daily hours
      "on" without chorea. RESULTS: While total daily medication costs after conversion
      increased by 21%, patients experienced either a comparable or an improved degree
      of disease control with Sinemet CR. Patients who were also taking selegiline were
      able to decrease selegiline expense by 20%. The costs of other adjunctive
      medications did not differ significantly after conversion. The cost-effectiveness
      analysis revealed an increase in postconversion on time by 2.2 hours (p =
      0.0001), accompanied by a $2.85 decrease in total cost per hour on without chorea
      (p = 0.11). CONCLUSIONS: Although Sinemet CR is more costly, it may be more cost
      effective in patients with motor fluctuations. Some patients may be able to
      reduce adjunctive medications.

PMID- 9762374
TI  - Concomitant rash and blood dyscrasias in geriatric psychiatry patients treated
      with carbamazepine.
AB  - BACKGROUND: Rashes and blood dyscrasias are disconcerting adverse effects
      associated with carbamazepine therapy. Rashes are quite common, as are mild blood
      dyscrasias, such as mild leukopenias. Fortunately, severe rashes and blood
      dyscrasias are rare. There are few reports on the relationship between
      carbamazepine-induced rashes and blood dyscrasias, including a prospective study
      in which rash appeared concomitantly with leukopenia and/or thrombocytopenia in
      10 patients, two case reports in which simultaneous rash and agranulocytosis
      occurred, and two case reports in which rashes served as harbingers of fatal
      aplastic anemia. CASE REPORTS: We report two cases of concomitant rashes and
      blood dyscrasias in geriatric psychiatry patients receiving carbamazepine therapy
      for bipolar disorder. One patient was found to have a severe leukopenia within
      several days after rash onset. The other patient was discovered to have a severe
      leukopenia and thrombocytopenia within about a month after rash onset.
      DISCUSSION: Current hematologic monitoring guidelines for carbamazepine rely
      heavily on the recognition of signs and symptoms of blood dyscrasias by
      clinicians and patients. We believe that our cases support the suggestion that
      patients who develop rashes receive more vigilant monitoring of the complete
      blood count, should carbamazepine therapy by continued. Given the currently
      available case reports and the fact that the incidence of drug-induced blood
      dyscrasias increases with advanced age, this recommendation may be particularly
      relevant for geriatric patients. CONCLUSIONS: Further study is required to
      establish whether carbamazepine-induced concomitant rashes and blood dyscrasias
      are valid associations insofar as monitoring is concerned.

PMID- 9762375
TI  - Minocycline-associated tooth staining.
AB  - OBJECTIVE: To describe a case of tooth discoloration in an adult after
      minocycline treatment for arthritis. CASE SUMMARY: A 68-year-old white women
      presented with blue-black staining of her lower anterior teeth after 4 months of
      minocycline therapy for arthritis. Her other medications are not known to cause
      discoloration of teeth. While the patient continued taking minocycline, her
      dentist was not able to remove the discoloration. Within 1 month after
      discontinuation of the minocycline, the dentist was able to remove the
      discoloration entirely. DISCUSSION: Minocycline, a synthetic derivative of
      tetracycline, has been shown to cause abnormal pigmentation of the skin, thyroid
      gland, nails, bone, sclera, and conjunctiva in adults. It also has been shown to
      cause tooth discoloration in a few patients. This case is unusual in that the
      tooth discoloration disappeared after discontinuing minocycline therapy.
      CONCLUSIONS: This complication of minocycline is more commonly thought of in the
      pediatric population. However, clinicians need to be aware of this adverse drug
      reaction, as this agent may be used increasingly in the treatment of adults with
      arthritis.

PMID- 9762376
TI  - Isoniazid-induced psychosis.
AB  - OBJECTIVE: To report a suspected case of isoniazid-induced psychosis in a 31-year
      old woman. CASE SUMMARY: A 31-year-old white woman without a prior psychiatric
      history presented with psychotic symptoms suspected to be related to prophylactic
      treatment with isoniazid after she tested positive to a tuberculin (purified
      protein derivative) test. The psychotic symptoms resolved partially after
      isoniazid was discontinued and completely after treatment with olanzapine was
      begun. The patient remained symptom-free 11 months after discharge from the
      hospital. DISCUSSION: Cases of isoniazid-related psychiatric disorders reported
      in the literature include psychosis, obsessive-compulsive neurosis, and mania.
      With the increasing prevalence of tuberculosis in the US, more people are
      expected to receive treatment for tuberculosis. Pyridoxine deficiency may play a
      role in the pathogenesis of isoniazid-induced psychosis. Such deficiency states
      may be detected indirectly by measuring urinary metabolites of tryptophan.
      CONCLUSIONS: Clinicians should be aware of this adverse effect of isoniazid and
      that it may present with a broad clinical picture.

PMID- 9762378
TI  - Issues surrounding tight glycemic control in people with type 2 diabetes
      mellitus.
AB  - OBJECTIVE: To review the prospective evidence surrounding the issue of tight
      glycemic control in people with type 2 diabetes mellitus and resultant long-term
      complications. DATA SOURCE: Conference proceedings and a MEDLINE search (1966
      February 1998) identified pertinent English-language publications on type 2
      diabetes in humans. Key search terms included insulin resistance, diabetes
      mellitus, non-insulin-dependent, macrovascular complications, microvascular
      complications, and intensive glycemic control. STUDY SELECTION: Selection of
      prospective epidemiologic and clinical studies were limited to those focusing on
      the management of type 2 diabetes. All articles with pertinent information
      relevant to the scope of this article were reviewed. DATA SYNTHESIS: The
      pathophysiology of type 1 and type 2 diabetes differ; however, both share chronic
      complications that significantly affect morbidity and mortality. People with type
      1 diabetes have an absolute deficiency of insulin, whereas people with type 2
      diabetes have varying degrees of insulin resistance and an inadequate
      compensatory insulin secretory response. The Diabetes Control and Complications
      Trial (DCCT) has clearly indicated that intense control of blood glucose in type
      1 diabetes prevents and slows the progression of microvascular (i.e.,
      retinopathy, nephropathy) and neuropathic complications. The Kumamoto study
      showed similar results in nonobese patients with type 2 diabetes. Intense insulin
      therapy in both populations has proven advantageous, thus supporting a common
      pathophysiologic process for the microvascular and neuropathic complications.
      Trends were seen toward fewer macrovascular (atherosclerotic disease)
      complications in the intensive insulin arm of the DCCT. Conversely, trends were
      seen toward an increase in macrovascular complications in the VA Cooperative
      study in people with type 2 diabetes using intensive insulin therapy. This may
      suggest a discordance in the pathophysiology of macrovascular disease between
      type 1 and type 2 diabetes. Additionally, it remains uncertain whether tight
      glycemic control prevents the onset or slows the progression of macrovascular
      disease. Two studies (the University Group Diabetes Program and the Veterans
      Affairs Cooperative Study on Glycemic Control and Complications in Type 2
      Diabetes) to date have examined pharmacotherapy options for patients with type 2
      diabetes and resultant macrovascular complications. It has yet to be determined
      whether any therapeutic intervention will decrease the morbidity and mortality of
      macrovascular disease in this population. CONCLUSIONS: In type 2 diabetes,
      limited prospective evidence does support tight glycemic control to help prevent
      or slow the progression of microvascular and neuropathic complications. It is
      uncertain whether tight glycemic control decreases macrovascular complications
      and which pharmacotherapeutic agent(s) is/are the best options. However, therapy
      that improves glucose control in combination with aggressive risk factor
      management should be initiated and enforced in patients with type 2 diabetes in
      an effort to reduce long-term complications.

PMID- 9762377
TI  - Rhabdomyolysis after correction of hyponatremia due to psychogenic polydipsia
      possibly complicated by clozapine.
AB  - OBJECTIVE: To report a case of rhabdomyolysis related to rapid correction of
      hyponatremia attributable to compulsive drinking of water, possible complicated
      by clozapine use. CASE SUMMARY: A 42-year-old white man treated with clozapine
      for schizophrenia was admitted for a generalized seizure. Marked hyponatremia due
      to psychogenic polydipsia was present. He developed a marked elevation of
      creatine kinase concentrations after correction of hyponatremia with hyperosmolar
      sodium solution, without clinical signs of rhabdomyolysis. DISCUSSION:
      Rhabdomyolysis associated with hyponatremia due to water intoxication has been
      reported in 17 patients to date. A possible explanation may lie within the
      framework of the calcium-sodium exchange across the skeletal muscle cell
      membrane. By increasing muscle cell permeability, clozapine treatment may
      possibly enhance the destruction of muscle cells. CONCLUSIONS: Hyponatremia due
      to water intoxication and concurrent use of clozapine should be considered in the
      differential diagnosis of rhabdomyolysis, especially in the severely
      psychiatrically disabled population.

PMID- 9762379
TI  - Novel antipsychotics and patient care in state hospitals.
AB  - OBJECTIVE: To review and highlight the opportunities and challenges of
      pharmacologic advances in the use of antipsychotics for the state hospital
      system. METHODS: A critical review was performed of studies published either as
      articles or abstracts, on the use of novel antipsychotics, particularly as they
      relate to the patient population within the state mental hospital system.
      FINDINGS: The recent availability of new antipsychotic medications within state
      facilities has resulted in more progressive treatment, reduced recidivism (and
      consequently cost savings), and preliminary evidence of preferential and superior
      treatment response in specific patient subgroups (e.g., those with aggression).
      At the same time, inpatient pharmacy budget increases and uncertainty in guiding
      the use of novel antipsychotics have influenced the availability of these agents
      in state hospitals. CONCLUSIONS: State hospital services have, by and large,
      embraced the developments in pharmacotherapy of schizophrenia. Optimal use of
      these new agents in this population requires additional information on their
      relative efficacy in specific patient subgroups.

PMID- 9762380
TI  - Update on drug interactions with azole antifungal agents.
AB  - OBJECTIVE: To review and update the incidence, mechanism, and clinical relevance
      of drug interactions with itraconazole, ketoconazole, and fluconazole. DATA
      SOURCES: Literature was identified by MEDLINE search (from January 1990 to May
      1997) using the name of each antifungal and the term "interaction" as MeSH
      headings. Abstracts were identified by literature citation and by review of
      Interscience Conference on Antimicrobial Agents and Chemotherapy from 1995 to
      1996. STUDY SELECTION: Randomized, controlled, double-blind studies were
      emphasized; however, uncontrolled studies and case reports were also included. In
      vitro data were selected from literature review and citations. DATA EXTRACTION:
      Data were evaluated with respect to study design, clinical relevance, magnitude
      of interaction, and recommendations provided. DATA SYNTHESIS: The incidence of
      fungal infections and consequent azole antifungal usage continues to increase. By
      virtue of their antifungal mechanism (i.e., inhibition of cytochrome P450 fungal
      enzyme systems), azoles have been investigated and implicated in several drug
      interactions. The magnitude of interactions can vary from trivial to potentially
      fatal, and also vary with specific azole and interactant. CONCLUSIONS: The azole
      antifungal agents represent a commonly used class of agents with a broad range of
      potential interactions. Recent data have increased our understanding of drug-
      drug interactions with azoles. Pharmacists are in a unique position to identify
      these interactions and to intervene to decrease their morbidity and improve
      patient care.

PMID- 9762381
TI  - Management of end-stage renal disease in children.
AB  - OBJECTIVE: To review the medical literature on management of end-stage renal
      disease (ESRD) and its complications in the pediatric patient. DATA SOURCES AND
      STUDY SELECTION: MEDLINE searches (1970-1997) of the English-language literature.
      Clinical trials and reviews of drug therapy management were included, and
      bibliographies were reviewed for relevant articles. DATA SYNTHESIS: Principles of
      renal replacement therapy in children have been expanded to include maintenance
      of fluid and electrolyte balance and to manage the complications of ESRD in
      children. Types of renal replacement and their complications are reviewed.
      Complications of ESRD are reviewed with emphasis on drug therapy management of
      anemia of chronic renal failure, growth retardation, and hypertension. A
      discussion of the use of vitamins and supplements to maintain bone and mineral
      homeostasis is provided, and specific recommendations for vaccination of children
      with ESRD are given. CONCLUSIONS: Children with end-stage renal failure present a
      unique challenge to the pharmacist. Renal replacement therapy for children with
      ESRD involves some form of dialysis and an intensive medication regimen.
      Complications must be treated with appropriate drug therapy. Drug therapy must be
      monitored closely for dosage adjustment, clinical response, drug interactions,
      and toxicity. Patients and families must receive continuous education and follow
      up to encourage compliance. The pharmacist must work closely with the healthcare
      team to optimize drug therapy and improve patient education and compliance.

PMID- 9762382
TI  - Medication bezoars: a literature review and report of a case.
AB  - OBJECTIVE: To describe a case of a medication bezoar and to review the clinical
      presentation, diagnosis, risk factors, pathogenesis, complications, and treatment
      of medication bezoars. DATA SOURCES AND STUDY SELECTION: A MEDLINE search
      (January 1966-December 1997) of the English-language literature pertaining to
      bezoars was performed. These articles were scanned, and literature specifically
      discussing medication bezoars was selected. Additionally, the reference sections
      of pertinent review and case reports were scanned for additional relevant
      literature. DATA SYNTHESIS: Bezoars are concretions of foreign material within
      the body. In the case of medication bezoars, these concretions occur within the
      digestive tract and are composed of medications and/or medication vehicles.
      Rarely, however, is bezoar formation solely due to a medication. In nearly all
      reported cases the patient had one or more significant risk factors that
      contributed to bezoar formation. The exact method by which medications bezoars
      form is dependent on the particular type or combination of medications involved.
      Bezoar formation may be associated with significant complications for the patient
      due to the presence of the bezoar and because of the effects of the medication
      within the bezoar. Treatment of medication bezoars depends largely on the
      location and the cause of the bezoar. CONCLUSIONS: Medication bezoars are a rare
      but potentially serious complication of medication use in certain patients. These
      patients often present with signs and symptoms consistent with an obstruction of
      the gastrointestinal tract and represent an even greater diagnostic challenge due
      to the rarity of this complication. These patients also face significant
      complications from both the bezoar and the medication within the bezoar. To date,
      treatment of medication bezoars involves mainly physical manipulation of the
      bezoar through lavage, endoscopic removal, or, in most cases, surgical removal.

PMID- 9762383
TI  - Drug and environmental factors associated with adverse pregnancy outcomes. Part
      II: Improvement with folic acid.
AB  - OBJECTIVE: To provide a comprehensive review of periconceptional folic acid
      supplementation and factors affecting folate supplementation trials. DATA
      SOURCES: A MEDLINE search was conducted through December 1997. Additional sources
      were obtained from Current Contents and citations from the references obtained.
      Search terms included folate, folic acid, neural tube defect, spina bifida, and
      anencephaly. STUDY SELECTION: Relevant animal and human studies examining the
      effects of folate were reviewed. DATA EXTRACTION: Data collected included: type
      of study, folate dosing, dietary folate intake, serum and red blood cell folate
      concentrations, type of defect(s) studied, vitamin usage, parental risk factors,
      factors affecting trial results. DATA SYNTHESIS: Nine key factors have been
      identified that affect outcomes of folic acid supplementation trials. Daily doses
      of 0.8 mg decreased the occurrence and doses of 4 mg decreased the recurrence of
      neural tube defects in randomized clinical trials. Since lower folic acid doses
      were effective in nonrandomized trials, research is needed to determine the
      lowest effective dosage. Other benefits involving pregnancy outcome are
      suggested. CONCLUSIONS: Women of childbearing age should take a daily folic acid
      supplement to reduce the risk of pregnancies resulting in infants with a neural
      tube defect and other potential adverse pregnancy outcomes. Further health
      benefits from folic acid supplementation are reviewed in Part III of this series.

PMID- 9762384
TI  - Providing patients with written medication information.
AB  - OBJECTIVE: To review the literature and provide recommendations for the
      development and dissemination of written medication information to patients and
      their care providers. DATA SOURCES: A MEDLINE search (1966-1997) of the English
      language literature was performed to identify articles pertaining to the
      development or use of written medication information. A search of the Internet
      was conducted by using Yahoo as the guide and "medication information" as the
      search term. Additional resources were obtained through texts, bibliographies,
      and catalogs from medical publishers. DATA EXTRACTION: Reports documenting the
      creation and use of written medication information systems were reviewed, as well
      as studies of readability and reading skills assessment. Examples of materials
      available for purchase by laypeople and healthcare providers were also examined.
      DATA SYNTHESIS: Current statistics support the widespread availability of written
      medication information for patients and care providers. The goal set forth by the
      Food and Drug Administration of having 75% of patients receive written
      information by the year 2000 appears achievable. However, there are still many
      issues to address. Content is not standardized, and materials are frequently
      written at reading levels higher than that of the average patient. The
      development and use of resources requiring only minimal reading skills and an
      increase in the availability of materials written in Spanish are needed.
      CONCLUSIONS: Written medication information provides a useful addition to
      counseling by healthcare professionals. A wide variety of prepared materials is
      available, as well as resources for those interested in developing tools for a
      specific patient, population, or setting. Healthcare professionals should be
      aware of the limitations of some resources. Content and readability must be
      appropriate for the intended audience for these tools to serve a useful role in
      patient education.

PMID- 9762385
TI  - Calcium in corticosteroid-induced osteoporosis.

PMID- 9762386
TI  - Treatment of croup with glucocorticoids.
AB  - Croup is a common upper airway disease in children that can range from mild and
      self-limiting to severe and fulminating. Typical treatment in the past has been
      mist therapy, although its effectiveness is still being debated. Studies have
      been published evaluating the efficacy of oral, nebulized, and intramuscular
      dexamethasone and nebulized budesonide, in a number of combinations and
      concentrations, in patients ranging in age from 3 to 72 months. The majority of
      the subjects in the studies were males and more than one-third of the patients in
      one study previously had croup. The studies have consistently pointed out that
      the use of oral, intramuscular, and nebulized steroids have been beneficial in
      patients with varying severity of croup. Nebulized budesonide has been shown to
      be effective, but is not currently available in the US. Based on this
      information, intramuscular or oral dexamethasone has been shown to be effective
      and, in some studies, safe and could be administered to patients presenting with
      moderate-to-severe croup.

PMID- 9762387
TI  - Clinical aspects of gene therapy.

PMID- 9762388
TI  - Indomethacin is inappropriate for use in the geriatric population.

PMID- 9762389
TI  - Comment: use and abuse of flunitrazepam.

PMID- 9762390
TI  - Comment: hyponatremia with venlafaxine.

PMID- 9762391
TI  - [When and how to treat sarcoidosis].

PMID- 9762392
TI  - [Smoking prevention in the school: results of a 3-year program].
AB  - Tobacco use poses one of the greatest health problems at school. Its prevention
      through health education should be assumed up by all members of the school
      community and health personnel (especially family and respiratory physicians). We
      designed an anti-tobacco program lasting three years aimed at all the students of
      the 6th, 7th and 8th grades at school as well as those in the pre-university
      years that was implemented in a rural area. This study reports the results of the
      attitudes of the 610 students (256 boys and 354 girls, between 11 and 20 years
      old) collected at the end of the program. 59.4% of the boys and 44.1% of the
      girls reported having smoked on some occasion. The mean age at the time of the
      first contact with tobacco was 11.8 +/- 2.4 years, this being significantly
      different between the boys and the girls. The main reasons for starting to smoke
      tobacco were quoted as peer pressure (57.1%) and curiosity (55.5%). That their
      parents smoked was only adduced as a reason by 29.5% of the students. Knowledge
      of the harmful effects of tobacco was limited and only 57% related tobacco
      smoking to lung cancer and only 41% to coronary pathology. At the end of the
      program 13.6% of the students involved smoked. 93.9% of those who quit smoking
      related this event to the program. Of those still smoking, 63.6% said they would
      like to quit. This justifies the need to reinforce the knowledge that will allow
      them to switch attitudes and stop smoking. Intervention programs in school
      populations have proved to be useful in the struggle to decrease smoking among
      school children. If an adolescent can avoid smoking it is likely that s/he will
      not smoke in adulthood. It is necessary to further develop this type of anti
      tobacco program as reflected in this paper.

PMID- 9762393
TI  - [Thoracic stab wounds].
AB  - Stab wounds are the most common cause of open chest wounds in our setting, with
      an incidence far higher than either wounds caused by firearms or bull horns. We
      describe a series of 49 patients, 44 (89.8%) men and 5 (10.2%) women. Mean age
      was 31 years. The 49 patients had suffered 72 stab wounds to the chest, of which
      30 (41.6%) were penetrating and 42 (58.3%) were non penetrating. The lesions
      observed were 11 (22.4%) cases of pneumothorax, 10 (20.4%) of hemopneumothorax, 6
      pulmonary lesions, 2 heart wounds and 1 extensively damaged diaphragm. Twenty
      four patients with non penetrating wounds and 8 with penetrating wounds were
      treated conservatively. It was subsequently necessary to drain the chest of only
      one. Of the remaining penetrating wounds, drains were inserted in six immediately
      and 11 underwent surgery. Complications developed in only 9 cases. One patient
      died as a result of abdominal lesions resulting from stab wounds directly to the
      abdomen. We are in favor of conservative management. Indications for more
      aggressive intervention are hypovolemic shock, cardiac tamponade or significant
      loss of fluid through the thoracic drain.

PMID- 9762394
TI  - [Characteristics of tuberculosis in a tertiary hospital during the years 1993
      1996. Influence of the coinfection with HIV].
AB  - To assess and compare epidemiological factors, clinical and radiological signs,
      laboratory results and drug resistance in patients with tuberculosis (TB) with
      and without AIDS. Retrospective study of TB diagnosed bacteriologically between
      January 1993 and December 1996 at Hospital Universitario La Fe. Annual rates were
      41.7, 47.1, 34.6 and 43.8 per 100,000 inhabitants in 1993 to 1996, respectively.
      AIDS was present in 22.4%. TB was pulmonary in 87% and 49.4% in patients without
      and with AIDS, respectively. Incidence was higher in the 25 to 34 age range.
      Prior contact with TB patients was established in 19.2% of cases. Pulmonary TB in
      patients with AIDS presented with normal lung X-rays in 30.1%; 16.2% of these had
      positive sputum cultures. Pulmonary cavitation was evident in 32.6% of TB
      patients without AIDS and 6.8% of those with AIDS. Pulmonary TB was diagnosed by
      culture of sputum taken at the time of admission in 25.9% of non AIDS patients
      and in 12.4% of patients with AIDS. Extrapulmonary TB was diagnosed by culture in
      most cases. Such forms predominated among TB plus AIDS patients, with most cases
      being ganglial and urogenital. Overall drug resistance was 8.3% (7.4% non
      AIDS/11.5% AIDS). Primary resistance (PR) was 6.3% and 7.1%, PR to hydrazides was
      5% and 5.4%, and secondary resistance was 32.4% and 33.3%. Drug resistance in non
      AIDS and AIDS patients, was associated with a history of TB and past treatment (p
      < 0.009), prior contact with TB patients (p < 0.004) and pulmonary cavitatin (p <
      0.02). TB with AIDS tends to occur in a younger population, is often
      extrapulmonary or with atypical lung involvement. Drug resistance is similar in
      patients with and without AIDS.

PMID- 9762395
TI  - [Relationship between tobacco smoke exposure and the concentrations of
      carboxyhemoglobin and hemoglobin].
AB  - To determine the carboxyhemoglobin (CO-Hb) predictive intervals in active and
      passive smokers and to obtain an equation expressing the relation of CO-Hb to
      number of cigarettes smoked, we studied 233 outpatients referred to an urban
      university hospital for arterial gas measurement. Patients were excluded if they
      were receiving oxygen therapy or had been hospitalized in the two months before
      the study. The patients were classified as non smokers (57), passive smokers
      (54), smokers of less than 11 cigarettes (22), smokers of 11 to 20 (41) smokers
      of 21 to 40 (44) and smokers of over 40 (15). All patients answered a
      questionnaire on exposure to tobacco smoke or other sources of CO. Blood gases
      and co-oximetry were measured in all patients. Mean CO-Hb and 95% confidence
      intervals were 1.53% (0.78-1.85%) in smokers and 2.59% (1.89-3.29%) in passive
      smokers. The linear equation that best expressed the relationship was CO-Hb =
      0.153 x number of cigarettes + 1.1 exposure to other sources (1 or 0) + 1.39 (SD
      0.84)%. Hemoglobin level was significantly higher in the two groups smoking more
      than 21 cigarettes. We conclude that the predictive intervals is 1.9% in non
      smokers who are not exposed to other sources of CO. Passive smokers have
      significantly higher levels of CO-Hb than non smokers. Heavy smokers have
      polycythemia.

PMID- 9762396
TI  - [Respiratory disease in the immigrant].

PMID- 9762397
TI  - [Antipneumococcal vaccines. Old controversies and new indications (II)].

PMID- 9762398
TI  - [Atypical carcinoid tumor of the thymus].
AB  - We report a male patient with atypical carcinoid tumor diagnosed by anterior
      mediastinotomy and biopsy after a mass was observed by chance on a chest film.
      The presence of neuroendocrine markers, notably chromogranin, cytokeratin,
      synapto-physin and neuro-specific enolase, facilitated diagnosis. Because the
      tumor was infiltrative, full surgical excision and radiotherapy to the
      mediastinum (50 Gy) were provided. We describe the incidence, clinical
      presentation, diagnosis, treatment and prognosis of these tumors.

PMID- 9762399
TI  - [Benign fibrous mesothelioma: report of 8 cases].
AB  - Benign fibrous mesothelioma (BFM) is a primary, isolated tumor of the pleura. In
      80% of patients the tumor originates in the visceral pleura. BFM is rare and
      localized malignant mesothelioma, whose prognosis and treatment is significantly
      different, must be considered as a differential diagnosis. We report 8 cases of
      BFM excised by thoracotomy. In 6 asymptomatic patients, diagnosis was based on
      radiological images. One patient with a large tumor suffered dyspnea, acropachia
      and hypertrophic osteoarthropathy. The last patient experienced long-lasting
      chest pain even though the tumor was small (3 x 3 x 1 cm). Diagnosis was before
      thoracotomy in 3 cases, 2 by punch biopsy (tru-cut) and the other by
      thoracoscopy. The results of pleural fluid analysis were nonspecific in 2 of the
      3 cases in which pleural effusion was present. Thoracotomy allowed removal of the
      entire tumor in all patients.

PMID- 9762400
TI  - [Esophagocele: a complication of the bipolar exclusion of the esophagus].

PMID- 9762401
TI  - [Cavitated chronic eosinophilic pneumonia with increased serum IgE. Is its
      differentiation from Churg-Strauss vasculitis possible?].

PMID- 9762402
TI  - [Cystic pulmonary disease: a rare form of sarcoidosis].

PMID- 9762403
TI  - [Cervical pulmonary hernia].

PMID- 9762404
TI  - [Directly observed treatment of tuberculosis].

PMID- 9762405
TI  - A proposed estimate of the tumor aggressiveness of human breast cancer using
      radiorespirometry.
AB  - The relationships between carcinomatous aggressiveness and the glucolytic
      metabolism, namely the rate of 14CO2 production from [U-14C] glucose, are
      obtained from human breast tissues using radiorespirometry. The values are
      estimated as the initial velocity (V) expressed in eta 14CO2 x min-1 x g-1 of
      fresh tissues by [U-14C] glucose metabolism. The aggressiveness of the breast
      carcinomatous is diagnosed by the SBR grade system. As two control normal
      tissues, (V) are 0.86 to 0.90 from non-cancer patients. In carcinomatous tissues
      (Vc), there is an increase from 1.53 to 3.14, but in the corresponding
      surrounding non-cancer tissues (Vn) these show a decrease from 2.20 to 0.22 for
      SBR I, SNR II to SBR III. The ratio between (Vc) and (Vn) are found, according to
      carcinomatous aggressiveness, as 1.45 to 1.54, 1.69, 2.35 to 2.86 and 4.82 to
      10.38 respectively for SBR I, lobular carcinoma, SBR II and SBR III; while the
      ratio is 1.04 for the normal tissue which come from non-cancer patients. The
      above results suggest the possibility of assessing the carcinomatous
      aggressiveness by radiorespirometry before a histopathological diagnosis, even in
      a lower aggressiveness as in SBR I cases which are difficult to diagnose and
      manage.

PMID- 9762406
TI  - Constitutive nitric oxide synthase in Saccharomyces cerevisiae.
AB  - After removing nonspecific immunoreactivities from crude extract by
      immunoaffinity chromatography, an immunoreactive-band at 60 kDa of constitutive
      nitric oxide synthase (cNOS) from Saccharomyces cerevisiae was detected by
      Western blot using mouse monoclonal anti-neuronal NOS (cNOS). The activity of
      yeast cNOS, which was prepared by either histone-agarose chromatography or anti
      neuronal NOS immunoprecipitation, was monitored by the formation of citrulline.
      Yeast cNOS was activated in the presence of calmodulin and arginine, whereas it
      was inhibited by L-NAME, a mammalian NOS inhibitor. Moreover, actinomycin-D
      decreased the extracellular and the intracellular levels of nitrate and nitrite
      which had been converted from NO. The results suggest that cNOS occurs in
      unicellular eukaryotes and the enzyme activity can be regulated.

PMID- 9762407
TI  - The potential role for CDC42 protein from rat brain cytosol in phospholipase D
      activation.
AB  - Phospholipase D (PLD) has been extracted from rat brain membranes and
      chromatographically enriched 70-fold. From the rat brain cytosol, Cdc42 with a Mr
      of about 24,000 and ADP-ribosylation Factor (Arf) with a Mr of about 18,000 have
      been purified to near homogeneity. PLD was activated better by purified cytosolic
      Arf than by the other small G proteins tested. Cdc42 purified from rat brain
      cytosol showed 70% of PLD activation activity exerted by cytosolic Arf,
      suggesting that Cdc42 may be one of the major G proteins involved in the
      activation of membrane-associated PLD. While Cdc42 or RhoA exhibited synergistic
      activation of PLD when administered in conjunction with Arf, Cdc42 and RhoA
      showed an additive effect when used together. It is possible that Arf and Rho
      family proteins may have different interaction sites on PLD. These findings
      support a role for GTP-binding proteins of the Rho family as well as Arf in the
      activation of membrane-associated PLD and further suggest that Cdc42 may be a
      major G protein involved in the PLD activation in rat brain.

PMID- 9762408
TI  - Lower arachidonic acid content and preferential beta-oxidation of arachidonic
      acid over palmitic acid in tumour cell lines as compared to normal lymphoid
      cells.
AB  - In several studies certain polyunsaturated fatty acids (PUFA) have been shown to
      be selectively tumouricidal or suppressive of tumour cell proliferation. The
      mechanism behind this phenomenon likely involves peroxidation of the PUFA and
      generation of free radicals to which tumour cells seem to be more sensitive than
      normal cells. In this report we have measured the total lipid content in
      separated lymphoid cells and several tumour cell lines, among which, T-cell
      leukaemia, monocytic leukaemia, melanoma, fibrosarcoma, lung carcinoma and colon
      adenocarcinoma are included. Generally these tumour cell lines contain only one
      half to one third of the relative amount of arachidonic acid (AA) as compared to
      freshly prepared lymphocytes and monocytes or lymphocytes kept in culture.
      Furthermore, when we measured the beta-oxidation in long term incubation of [1
      14C] AA and compared it with that of [1-14C] palmitic acid we found that several
      of the tumour cell lines showed a preference for AA over palmitic acid in the
      tumour cell lines whereas the opposite was observed for normal lymphoid cells.

PMID- 9762409
TI  - A human B cell line AF10 expressing HIL-17.
AB  - AF10, a human B cell line, is a mycoplasma-free variant cloned from the human IgE
      myeloma cell line U266. Total RNA isolated from the AF10 cells was used as
      template for RT-PCR, and a specific product of about 411bp corresponding to the
      coding region of hIL-17 lack of a leading sequence obtained. The sequence of the
      RT-PCR product is the same to that reported in the literature. The expressed rhIL
      17 in E. coli can induce 10- to 15-fold increase of IL-6 secretion by mouse
      fibroblast 3T3 cells. It is for the first time until now that hIL-17 messager has
      been detected in B cell. There may exist some potential relationship between hIL
      17 and myeloma cells.

PMID- 9762410
TI  - Hepatic and renal metallothionein induction following single oral administration
      of gallium arsenide in rats.
AB  - Metallothionein genes (MT) are inducible by a variety of agents, including heavy
      metals. We report the induction of MT expression by gallium arsenide (GaAs), a
      superior intermetallic semiconductor material at two time intervals following
      single oral exposure in rats. The data is also supplemented with two additional
      groups exposed to gallium (III) as gallium oxide and arsenic (III) as sodium
      arsenite to determine which of the two moieties in GaAs is responsible for any
      such possible effects. The results indicate that GaAs administration does
      significantly induces MT in hepatic tissues accompanied by an increase in
      cytosolic glutathione, arsenic, zinc and copper concentration. It thus proves
      that arsenic moiety is chiefly responsible for such an effect.

PMID- 9762411
TI  - Spin trapping for nitric oxide produced in LPS-treated mouse using various new
      dithiocarbamate iron complexes having substituted proline and serine moiety.
AB  - Four dithiocarbamate derivatives of 4-substituted L-proline and N-methyl-L-serine
      were synthesized, and their iron complexes were prepared in Tris-HCl buffer
      solution. These complexes were used as spin trapping reagents for nitric oxide in
      ESR spectrometry, and compared with each other in regard to their spin trapping
      properties in vivo. When the synthesized complexes were injected to
      lipopolysaccharide-treated mice intravenously, the nitric oxide adducts were
      detected both in the liver and in the blood except N-dithiocarboxy-4
      (methoxymethyl)oxy-L-proline iron complex, whose nitric oxide adduct was detected
      mostly in the blood. When the exogenous nitric oxide adduct of this complex was
      injected, it was not detected in the liver, too. It is considered that this
      complex can trap nitric oxide in the blood by excluding the accumulation of the
      nitric oxide adduct in the liver.

PMID- 9762412
TI  - Modulation of MAP kinase signaling and growth characteristics by the
      overexpression of protein kinase C in NIH3T3 cells.
AB  - This study was performed to examine effects of the overexpression of protein
      kinase C (PKC) isoforms (i.e., beta I, beta II, gamma, delta, eta, and zeta) on
      mitogen-activated protein (MAP) kinase (Erk-1 and -2) signaling and growth
      characteristics of NIH3T3 cells. Phorbol ester (PMA) activated endogenous and
      ectopically expressed PKC alpha, beta I, beta II, gamma, delta, epsilon, and eta.
      Overexpression of the examined PKC isoforms enhanced PMA-induced MAP kinase
      activation. Potentiation of MAP kinase activation was also observed upon
      stimulation of cells with platelet-derived growth factor (PDGF) although there
      was no indication for the activation PKC isoforms by PDGF. Inhibition of PKC
      blocked PMA- but not PDGF-induced MAP kinase activation. Thus, potentiation of
      PDGF-induced MAP kinase activation appears to be independent to PKC activity,
      while PMA-induced MAP kinase activation requires PKC activity. The ability of PKC
      isoforms to potentiate MAP kinase activation is not related to the growth
      characteristics of cells because individual PKC isoforms differentially regulated
      maximum density and proliferation of cells.

PMID- 9762413
TI  - RGD-containing trypsin with both platelet aggregation inhibitory activity and
      proteolytic activity.
AB  - Arg-Gly-Asp (RGD) motif mediates cell adhesion as a major determinant in
      interactions of disintegrins with cell surface receptors. In order to obtain a
      mutant trypsin with both high affinity to integrins and retained proteolytic
      activity, RGDS and RGD were inserted into a rigid turn region and a flexible loop
      of trypsin, respectively. Wild type trypsin and substituted mutant trypsins,
      37RGDS and 77RGD, were expressed in E. coli and purified. Kinetic properties,
      autolytic stability as well as platelet aggregation inhibitory activity of both
      37RGDS and 77RGD were determined. 37RGDS and 77RGD give retained proteolytic
      activities of 34% and 87%, respectively, and both become less stable to
      autolysis. 37RGDS shows an obvious inhibition rate of 29% for platelet
      aggregation and 77RGD gives a rather weak rate of 14% at the same protein
      concentration of 3.5 microM, while the wild type trypsin shows no inhibitory
      activity.

PMID- 9762414
TI  - Effect of cholesterol/phospholipid ratio on stimulatory GTP-binding protein
      function.
AB  - The effect of different cholesterol/phospholipid (C/P) ratios on the coupling
      function between stimulatory GTP-binding protein(Gs) and adenylyl cyclase (AC) in
      proteoliposomes, and its relationship to the conformational change of Gs were
      investigated. The results showed that Gs activities of both binding GTP gamma S
      and stimulating adenylyl cyclase were the highest in proteoliposomes with a
      proper content of cholesterol similar to physiological situation while the lowest
      with higher cholesterol content similar to pathological situation. In addition,
      the conformational change of Gs in proteoliposomes was also detected by steady
      state and nanosecond time-resolved fluorescence using acrylodan as a probe. It is
      suggested that a proper C/P ratio similar to physiological situation regulates
      the function of Gs by inducing a change in the physical state of lipid bilayer,
      which would favor the formation of a suitable conformation of Gs with higher
      activities of both binding GTP and stimulating adenylyl cyclase. But if C/P ratio
      is higher, such as in pathological situation, this is unfavorable for motion of
      Gs in membrane, which results in inhibition of Gs function significantly.

PMID- 9762415
TI  - Monoclonal antibodies directed against lipopolysaccharide of Legionella
      pneumophila serogroup 1.
AB  - The monoclonal antibodies (MAbs) against lipopolysaccharide of virulent strain of
      Legionella pneumophila serogroup 1 were produced. Three most productive hybrid
      clones (5F4, 5F10 and 2C9) were selected from fusions of mouse myeloma cells with
      spleen cells from BALB/c mice, immunized with bacterial outer membrane antigens.
      All generated clones were IgG-secreting. The MAbs had narrow strain specificity
      and showed no cross-reactions with other unrelated bacterial species. These
      antibodies were tested in sandwich ELISA. The results suggest that the MAbs could
      be used for diagnostic purposes.

PMID- 9762416
TI  - TNF alpha-induced aerobic synthesis of ATP on plasma membranes of target cells.
      The relation to the expression of the nuclear oncogene c-myc.
AB  - The accumulation of ATP by preparations of plasma membranes enriched particles
      (PMEP) isolated from rat hepatocytes, murine splenocytes and human T-lymphocytes
      has been investigated after the binding of human and murine tumour necrosis
      factors (TNF alpha) to their specific receptors. The TNF alpha-induced expression
      of the nuclear oncogene c-myc in intact hepatocytes has been also studied. TNF
      alpha induced the marked biosynthesis of ATP on PMEP of hepatocytes and
      splenocytes within the first minute of incubation. The biosynthesis of ATP was
      independent of the activity of adenylate kinase and only occurred in the presence
      of all the components of aerobic phosphorylation and the electron acceptor,
      cytochrome C or diferric transferrin. The level of ATP on PM correlated with the
      degree of expression of the nuclear oncogene c-myc in the same target cells.
      Adriamycin totally suppressed the biosynthesis of ATP on PM and simultaneously
      inhibited the expression of c-myc. The ATP synthesized on PM is suggested to be
      involved in transduction of the proliferative or growth signal to the cell
      nucleus.

PMID- 9762417
TI  - Epitope mapping of anti-troponin I monoclonal antibodies.
AB  - Two groups of monoclonal antibodies (MAbs) specific to human cardiac troponin I
      (cTnI) were generated by immunization of mice by isolated cTnI (group I, 16 MAbs)
      or by the whole troponin complex (group II, 15 MAbs). Two sets of overlapping
      decapeptides covering the complete sequence of cTnI were prepared and used for
      epitope mapping by SPOT technique. Majority of MAbs (28 out of 31) interacts with
      synthetic peptides thus indicating that they recognize liner epitopes. MAbs
      raised against isolated cTnI preferentially recognize epitopes located at the N-
      or C-terminal ends of cTnI. Nine out of fifteen MAbs raised against whole
      troponin complex interact with epitopes located in the N-terminal part of cTnI.
      Generation of MAbs recognizing both isolated cTnI and cTnI inside of troponin
      complex and mapping their epitopes provides reliable detection of TnI in serum of
      patients with acute myocardial infarction.

PMID- 9762418
TI  - The effect of interferon therapy on erythrocyte membrane Na+,K+ ATP activity in
      patients with chronic hepatitis B and C virus infections.
AB  - In order to evaluate the effect of alpha interferon on erythrocyte membrane
      Na+,K+ ATPase (EC 3.6.1.37) activity, 10 patients with chronic hepatitis B virus
      (HBV) infection and 8 patients with chronic hepatitis C virus (HCV) infection
      were investigated. Erythrocyte membrane Na+,K+ ATPase activity was determined in
      controls and in patients with HBV and HCV infection. Na+,K+ ATPase activity was
      significantly less in untreated patients with (HBV) infection (n = 20; 0.134 +/-
      0.073 mumol of phosphate produced per milligram of protein per hour) and (HCV)
      infection (n = 11; 0.144 +/- 0.049) when compared to the controls (n = 10; 0.219
      +/- 0.055). Among these subjects patients were treated with interferon and
      following treatment, significant elevation of Na+,K+ ATPase activity was seen in
      patients with HCV (n = 8; 0.183 +/- 0.044; P = 0.049) and HBV (n = 10, 0.213 +/-
      0.095, P = 0.0069) infections when compared with the pre-treatment values (n = 8;
      0.152 +/- 0.050) and (n = 10, 0.131 +/- 0.083), respectively. Normalization of
      serum alanin amino transferase levels (ALT) at treatment cessation was seen in 8
      of 10 (%80) HBV infected patients of whom 2 of 8 (%25) had sustained ALT
      responses within three months after the end of treatment. In HCV infected
      patients 1 of 8 (%12.5) had sustained response following treatment. At the end of
      treatment, although Na+,K+ ATPase was restored in both of the patients groups,
      relative changes in enzyme activity in relation to relative reduction in ALT
      levels as a response to IFN therapy were not correlated.

PMID- 9762419
TI  - Activation of apoptotic caspase-3 and nitric oxide synthase-2 in buccal mucosa
      with chronic alcohol ingestion.
AB  - Apoptosis, the process of programmed cell death, involves activation of caspase
      proteases cascade that remains under the regulatory control of nitric oxide. In
      this study, we investigated the activity of a key apoptotic protease, caspase-3,
      and the expression of nitric oxide synthase-2 (NOS-2) associated with buccal
      epithelial cells apoptosis induced by chronic ethanol diet. The assays revealed
      that a 7.9-fold enhancement in buccal epithelial cells apoptosis, observed in the
      alcohol diet group, was accompanied by a 37.6-fold increase in caspase-3 activity
      and a 10.1-fold increase in NOS-2. Furthermore, the expression of NOS-2 showed a
      positive correlation (r = 0.92) with the extent of changes induced in caspase-3
      activity. These results implicate caspase-3 in the process of alcohol-induced
      epithelial cells apoptosis, and point towards participation of NOS-2 in the
      amplification of the cell death signaling cascade.

PMID- 9762420
TI  - A comparative study by a single chromatographic procedure of glycolytic
      regulatory kinase isozymes in rat erythroid cells as a function of
      differentiation-maturation process.
AB  - The isozymes of three glycolytic regulatory kinases: hexokinase,
      phosphofructokinase and pyruvate kinase are fractionated by a single ion exchange
      chromatographic procedure on DEAE-cellulose. Enriched-erythroblast bone marrow
      cells showed two heterogeneous peaks, each consisting of two overlapping peaks:
      one major and one minor peak, but only two isozymes were observed in
      reticulocytes and erythrocytes. Phosphofructokinase showed multiple isozymic
      forms in the three cell populations, but while in erythroblasts the main one
      eluted in the last fractions, in reticulocytes and erythrocytes it eluted in the
      early fractions. Pyruvate kinase showed a main early activity peak with a
      shoulder in erythroblasts, reticulocytes and erythrocytes but the response to the
      allosteric effectors (fructose-1,6-bisphosphate and ATP) suggests the presence of
      different pyruvate kinase isozymes in reticulocytes and erythrocytes.

PMID- 9762421
TI  - Glutathione metabolism and glutathione S-conjugate export ATPase (MRP1/GS-X pump)
      activity in cancer. I. Differential expression in human cancer cell lines.
AB  - Mg(2+)-dependent vanadate-sensitive glutathione S-conjugate ATPase (GS-X pump)
      activity is a common feature of some ATP-binding cassette (ABC) transporters,
      such as the multidrug resistance-associated protein (MRP1) gene product, that
      exports biologically active electrophiles after their conjugation with
      intracellular glutathione (GSH) from normal and cancer cells. Antitumor
      electrophiles (e.g. naturally occurring cyclopentenone prostaglandins and
      anticancer chemicals) can be intracellularly conjugated with GSH via a
      glutathione S-transferase catalyzed reaction and be eliminated through GS-X pumps
      thus threatening cancer chemotherapeutics. Since different sensitivities to
      antitumor electrophiles are shown by different cell types, the ability of several
      human cancer cell lines to produce and export S-(2,4-dinitrophenyl)-glutathione
      (DNP-SG) conjugate through the GS-X pump, using whole cells and inside-out
      membrane vesicle preparations, is investigated. Different cancer cell lines
      exhibited characteristically different GS-X pump activity. In particular, HEp-2
      larynx carcinoma cells possess an elevated DNP-SG export rate through the GS-X
      pump compared with HeLa, K562, U937 or HL-60 cells, which exhibit the lowest
      activity. The differences in DNP-SG export rates are not due to decreased
      glutathione S-transferase activity or impaired de novo synthesis of GSH. The
      findings suggest that the GS-X pump may be involved in the modulation of the
      biological activity of both naturally occurring electrophiles and anticancer
      drugs. The differential expression of GS-X pumps may lead to an improved
      understanding of multidrug resistance and may be exploited in the development of
      new therapeutic strategies for the treatment of cancer patients.

PMID- 9762422
TI  - Glutathione metabolism and glutathione S-conjugate export ATPase (MRP1/GS-X pump)
      activity in cancer. II. Cell-to-cell variability, relation with cellular
      activation state and functional absence of GS-X pump in lymphocytes.
AB  - A severe complication in late-stage cancer patients is host immunosuppression. It
      is suggested that overproduction of the highly cytostatic and cytotoxic
      antiproliferative cyclopentenone prostaglandins (CP-PGs) within the plasma of
      cancer-bearing subjects may contribute to immunosuppression. Lymphoid tissues of
      Walker 256 tumor-bearing rats accumulate large amounts of CP-PGs while the tumor
      tissue itself does not. Moreover, tumor cells may present differential
      sensitivity to CP-PGs due to the expression of the multidrug resistance
      associated protein (MRP1) gene product which shows a Mg(2+)-dependent vanadate
      sensitive glutathione S-conjugate export ATPase (GS-X pump) activity that
      extrudes CP-PGs from cells as glutathione S-conjugates. In this study, the
      possibility that deficient GS-X pump activity in immune cells that may be
      involved in the accumulation of CP-PGs is investigated. Rat lymph node
      lymphocytes do not exhibit any notable activity even when mitogen-stimulated.
      Conversely, although rat peritoneal resident (quiescent) or thioglycollate
      stimulated (inflammatory) macrophages exhibit low GS-X pump activity, Bacillus
      Calmette-Guerin (BCG)-activated macrophages show a notable rise in the activity
      of the ATPase, suggesting that the cellular activation state may modulate GS-X
      pump activity/expression and that, under appropriate stimuli (e.g., during immune
      response) macrophages may provide a self-defense against electrophilic CP-PGs by
      forming GS-conjugates that can be extruded from cells through the GS-X pump. ras
      oncogene expression may be linked with MRP1/GS-X pump expression/activity, since
      C2C12 promyoblasts transformed by v-H-ras transfection doubled GS-X pump
      activity. These results support the proposition that the accumulation of CP-PGs
      and the immunosuppression of tumor-bearing subjects may be attributed to a lack
      of GS-X pump activity/expression in lymphocytes.

PMID- 9762423
TI  - Effects of the antiproliferative cyclopentenone prostaglandin A1 on glutathione
      metabolism in human cancer cells in culture.
AB  - Homeostatic mechanisms for the maintenance of glutathione (GSH) are fundamental
      in the provision of a cellular defense against electrophilic/oxidant challenges.
      Cyclopentenone prostaglandins (CP-PGs) are powerful antiproliferative endogenous
      substances that may act as electrophilic regulating compounds, by virtue of the
      presence of an alpha,beta-unsaturated carbonyl group in the cyclopentane ring.
      Nevertheless, differential resistance to CP-PG cytotoxic/cytostatic effect has
      been reported in different cell types. It is reported that the
      activity/expression of gamma-glutamylcysteine synthetase (gamma-GCS, the rate
      limiting enzyme in GSH biosynthesis) can be inducibly activated by electrophiles,
      including CP-PGs. The response of the human cancer strains HEp-2 (larynx
      carcinoma) and HL-60 (promyelocytic leukemia) cells to treatment with the CP-PG
      PGA1 in culture was investigated by evaluating the time-course of GSH synthesis
      and activity of enzymes of GSH metabolism, other than gamma-GCS, after PGA1
      addition. HEp-2 cells, being more resistant to PGA1 cytotoxic and cytostatic
      effects, have basal GSH levels that were 2.4-fold higher than that of HL-60
      cells. The activities of GSH S-transferase (GST), glutathione reductase (GSRd)
      and glutathione peroxidase (GSPx) are constitutively higher in HL-60 cells than
      in HEp-2 cells (respectively, 17.0-, 28.5- and 12.3-fold). When challenged with
      PGA1, both cell types exhibited a dose-dependent rise in GSH content that was
      maximal 18 h after PGA1 addition and was preceded by a rise in GST and GSRd
      activities in both cell types (at 12 h). GSPx activity increased only in HEp-2
      (PGA1 evoked a 93.4%-inhibition in HL-60 cells). Moreover only HEp-2 cells
      exhibited early capacity to enhance GSH content (1-2 h just after PGA1 addition).
      These results and earlier data showing that leukemia cells are sensitive to CP-PG
      treatment suggest that deficiencies in GSH metabolism may be strategically in
      therapeutic approaches to the treatment of human leukemias.

PMID- 9762424
TI  - A new PCR-based approach to a fast search of a wide spectrum of cry genes from
      Bacillus thuringiensis strains.
AB  - A pair of highly degenerated primers was adapted to carry out a single-step PCR
      detection of any known and probably unknown cry genes of classes cry1, cry4 and
      cry9 encoding for 130 kDa protein delta-endotoxins in the natural Bacillus
      thuringiensis (BT) strains. The Southern hybridization of the product has
      demonstrated that essentially remote cry-genes like cry1Aa and cry9A (cryIG)
      could be represented in the single amplificate if they are simultaneously present
      in the genome of the analyzed strain. Four genes were detected by the proposed
      scheme in the BT ssp. galleriae 11-67. One of them, gene cry1Ga1 was originally
      found and cloned using the PCR-amplification product obtained from the genomic
      DNA of this strain as a probe. The new gene was completely identical to one
      cloned by B. Lambert (unpublished, EMBL accession number Z22510) and essentially
      related to cryIM (EMBL accession number Y09326), renamed according to the new
      nomenclature as cry1Ga2.

PMID- 9762425
TI  - Anchored oligo(dT) primers for automated dye terminator DNA sequencing.

PMID- 9762426
TI  - Rapid DNA purification from agarose gels using 96-well format, centrifuge-driven
      filtration.

PMID- 9762427
TI  - Sodium vanadate treatment as a shortcut following alkaline phosphatase cleavage.

PMID- 9762428
TI  - Photographic recording of fluorescent DNA bands on agarose gels.

PMID- 9762429
TI  - Allele-specific, inverse-PCR amplification for genotyping MN blood group.

PMID- 9762430
TI  - PCR-mediated mutagenesis in sequences recalcitrant to homogeneous amplification.

PMID- 9762431
TI  - Repetitive elements amplified during differential display.

PMID- 9762432
TI  - Use of Staphylococcus aureus protein-A sub-domains as a tag for the sensitive
      detection of recombinant fusion proteins.

PMID- 9762433
TI  - Purification of Ig-fusion proteins from medium containing Ig.

PMID- 9762434
TI  - Inexpensive motion detectors for quantification of animal activity.

PMID- 9762435
TI  - Simple blocking system for use with maleimide-labeled nucleic acid probes.

PMID- 9762436
TI  - Clinical cancer trial information and specimen resources.

PMID- 9762437
TI  - Peak height pattern in dichloro-rhodamine and energy transfer dye terminator
      sequencing.
AB  - Establishing the pattern in peak heights within local sequence contexts improves
      the accuracy of base calling and the identification of DNA sequence variations in
      dye-terminator cycle sequencing. We have systematically examined pairs of
      sequence-tagged sites (STSs) that vary at only a single nucleotide to determine
      how base changes influence the peak heights of neighboring bases in sequencing
      traces generated by two recently commercialized dye-terminator chemistries, the
      dichloro-rhodamine (dRhodamine) and the energy transfer (BigDye) terminators. For
      sequencing traces generated with the dRhodamine terminators, the peak height of a
      particular base in 28 of 64 possible 3-base windows (44%) can be predicted by
      knowing just one or two bases 5' to the base in question. For those generated
      with the BigDye terminators, the peak height of a particular base in 23 of 64
      possible 3-base windows (36%) can be predicted by knowing the local sequence
      context. When the peak heights are binned slightly differently, 75% (48 out of 64
      cases) of the base peaks generated by both dRhodamine and BigDye terminators fall
      in the middle half, confirming that the peak patterns of these two new dye
      terminator chemistries are much more even than those found in the original
      rhodamine dye terminator sequences.

PMID- 9762438
TI  - Rapid acquisition of unknown DNA sequence adjacent to a known segment by
      multiplex restriction site PCR.
AB  - The determination of unknown DNA sequences around a known locus has important
      applications in molecular genetics, specifically in genomic walking and genome
      mapping. Several PCR-based methods have been reported to address this issue, but
      they often involve multiple, time-consuming steps. We have previously described a
      technique known as restriction site PCR (RS-PCR) that allows sequence acquisition
      faster than the existing methods. The method involves PCR using four separate
      universal primers that are representative of given restriction enzyme sites (RS
      primers), and a specific primer from one end of the known sequence. We have now
      significantly improved the technique by mixing the four universal primers into
      one PCR tube with the first specific primer. This is followed by a nested PCR
      with the mixed RS primers and an internal specific primer, after which the
      product is sequenced by direct automated sequencing. The technique, called
      multiplex RS-PCR (mRS-PCR), is reproducible and can be used to obtain unknown
      sequence adjacent to known sequences in both the upstream and downstream
      directions. We illustrate the application of mRS-PCR in the acquisition of
      approximately 780 bp of genomic sequence starting from a known sequence of
      approximately 120 bp. Multiplex RS-PCR appears to be the fastest of all methods
      that address the issue of unknown sequence retrieval adjacent to a known region.

PMID- 9762439
TI  - Highly sensitive northern hybridization using a rapid protocol for downward
      alkaline blotting of RNA.
AB  - A simple and fast RNA gel blot procedure is described that uses 50 mM NaOH to
      simultaneously transfer and fix RNA to a positively charged nylon membrane. The
      RNA is transferred in a downward direction, and transfer is routinely completed
      within 2.5 h. The resulting blots give increased sensitivity over existing
      methods without affecting RNA integrity and can be used in both radioactive and
      nonradioactive detection procedures.

PMID- 9762440
TI  - Limitations for purification of murine interleukin-18 when expressed as a fusion
      protein containing the FLAG peptide.
AB  - As a strategy to purify recombinant murine Interleukin (IL)-18, we cloned the
      mature coding region of this protein into the pFLAG-1 expression system. The
      intent was to use the FLAG peptide "tag" as an amino terminal addition to IL-18
      so that purification of this fusion protein (FLAG-IL-18) on anti-FLAG antibody
      affinity columns could be performed. While significant amounts of recombinant IL
      18 were present in E. coli lysates, only a small portion of this material could
      be recovered on immunoaffinity columns conjugated with an anti-FLAG antibody.
      Surprisingly, the majority of recombinant IL-18 present in E. coli (strain JM83)
      bacterial lysates did not contain the FLAG peptide and therefore did not bind to
      immunoaffinity columns conjugated with an anti-FLAG antibody. However, we found
      that the BL21 strain of E. coli, which has reduced endogenous protease activity,
      could express the majority of recombinant IL-18 as the fusion protein, FLAG-IL
      18. Taken together, these studies show that it is necessary to consider whether
      protease sites formed at the FLAG-protein junction can be easily cleaved by the
      bacterial strain used to express the fusion protein.

PMID- 9762441
TI  - Isolation of differentially expressed genes by combining representational
      difference analysis (RDA) and cDNA library arrays.
AB  - The difference products (DP) of representational difference analyses (RDA) were
      used as hybridization probes on cDNA arrays. The effectivity of RDA products
      obtained with increasing driver/tester ratios (DP 1 = 100:1, DP 2 = 800:1 and DP
      3 = 400,000:1) to isolate differentially expressed genes was compared with the
      effectivity of conventional differential hybridizations. Pacreatic cancer and
      control tissues were used as a test system to isolate differentially expressed
      genes. The use of RDA products as hybridization probes showed two major
      advantages: (i) a reliable identification of true differential signals; and (ii)
      only one autoradiograph had to be analyzed, which eliminated the need for a
      laborious subtraction of signal intensities obtained with different cDNA probes.
      Increasing driver/tester ratios in iterative rounds of RDA delivered more
      specific results, though the total yield of differential clones was gradually
      reduced. In this situation, the intermediate RDA product DP 2 provided the best
      compromise.

PMID- 9762442
TI  - Fission yeast expression vectors adapted for positive identification of gene
      insertion and green fluorescent protein fusion.
AB  - A pYZ series of fission yeast expression vectors, derivatives of the pREP series,
      was designed to allow positive identification of cloned gene insertion and fusion
      to the green fluorescent protein (GFP) gene for in vivo analysis of gene
      expression. To validate this new vector system, the human immunodeficiency virus
      type 1 (HIV-1) vpr gene of viral isolate pNL4-3 was expressed in the pYZ1N
      vector. Vpr-induced phenotypic changes were the same as those observed with vpr
      expressed from pREP1N. Consistent with observations in mammalian cells, a Vpr-GFP
      fusion protein localizes on the nuclear membrane of fission yeast cells.
      Additionally, we were able to detect a naturally occurring mixture of vpr genes
      from a plasma sample of an HIV-infected pediatric long-term surviving patient.
      These pYZ vectors expedite gene cloning for general purposes and are particularly
      suited for largescale random gene screening.

PMID- 9762443
TI  - Quantitation of mixed-base populations of HIV-1 variants by automated DNA
      sequencing with BODIPY dye-labeled primers.
AB  - Direct DNA sequencing of human immunodeficiency virus type 1 (HIV-1) pol and env
      gene regions was characterized for accuracy and precision. Restricted maximum
      likelihood (REML) analysis of molecular clone reconstruction experiments using a
      primer-walking strategy showed that the BODIPY and BODIPY energy-transfer (BET)
      dye primers sets were significantly more accurate in quantitating heterogenous
      base mixtures than the fluorescein/rhodamine dye primers. Of the three sets
      examined, the BET dye primers were the most accurate. The improved accuracy
      correlated with the reduced emission band-widths of BODIPY and BET dye primers
      and the more uniform signal intensities of BET dye primers. However, comparing %
      coefficients of variation (CV) for the three dye primer sets, revealed that
      BODIPY dye primers gave better precision than both BET and fluorescein/rhodamine
      dye primer sets. Several sequence-dependent motifs were identified that showed
      specific nucleotide-biased incorporation and were determined to be the major
      variable component of the total %CV. Taken together, these results show that
      BODIPY and BET direct DNA sequencing can accurately and precisely characterize
      complex mixed-base populations.

PMID- 9762444
TI  - Large DNA fragment sizing using native acrylamide gels on an automated DNA
      sequencer and GENESCAN software.
AB  - We have investigated the potential of the PE Applied Biosystems Model 373
      Automated DNA Sequencer and GENESCAN software to size minisatellite alleles
      ranging in size from 230 bp to 2.5 kbp. We report on the use of a native (non
      denaturing) acrylamide gel system and fluorescent dUTP labeling of PCR products.
      The observed variability in size calling ranged from +/- 0.4-bp standard
      deviation (SD) at the lower end of the size range to +/- 37.5-bp SD for the
      largest allele. Both within-gel and between-gel variability in sizing increased
      with larger alleles, in particular when sizes exceeded 2 kbp. Size-calling
      differences were observed dependent on the method used to fluorescently label the
      PCR products and with the fluorescent dye type and concentration used in
      incorporation. The benefits and limitations of the current GENESCAN software in
      sizing large DNA fragments are also discussed.

PMID- 9762445
TI  - DAF optimization using Taguchi methods and the effect of thermal cycling
      parameters on DNA amplification.
AB  - Taguchi methods, which are widely applied in industrial process design, were used
      to optimize DNA amplification finger-printing (DAF). Quadratic loss functions
      that penalize deviations from prediction values and L9 (3(4)) and L18 (3(8))
      orthogonal arrays revealed effects and interactions of amplification reaction
      components and thermal cycling parameters. Analysis of variance (ANOVA)
      decomposed the contribution of individual factors to the experimental response
      (amplification yield and product number), while verification experiments
      established that optimum conditions were predictable, verifiable and
      reproducible. While several amplification components (primer, magnesium and
      enzyme) conditioned the amplification reaction, annealing temperature and time
      were the only important thermal cycling contributing factors. The Taguchi
      strategy defined a robust and transportable amplification protocol based on high
      annealing temperatures (typically 48 degrees C) and primer concentrations
      (typically 8 microM), which can be applied to the fingerprinting of a wide range
      of DNA templates of plant and fungal origin. The general strategy of robust
      experimental design holds potential as an optimization tool for other methods in
      molecular biology.

PMID- 9762447
TI  - DNA nicks and increased sensitivity of DNA to fluorescence in situ end labeling
      during functional spermiogenesis.
AB  - Terminal transferase can be used to quantitate DNA strand breaks in situ by
      labeling free 3'-hydroxyl ends with exogenous nucleotides. Endogenous nicks in
      DNA temporally appear and disappear during functionally significant structural
      rearrangements of chromatin. Fluorescence in situ end labeling of mouse and rat
      testicular cells demonstrated that functional spermiogenesis is associated with
      abundant DNA nicks that occur in elongating spermatids, most likely as a result
      of nucleoprotein changes during terminal differentiation. Detectable DNA breaks
      were not observed in round spermatids and epididymal sperm.

PMID- 9762448
TI  - lambda RNA internal standards quantify sensitivity and amplification efficiency
      of mammalian gene expression profiling.
AB  - There is an increasing interest in being able to document simultaneous levels of
      multiple mRNAs from limited amounts of mammalian tissue. The combination of
      amplified antisense RNA (aRNA) and reverse Northern blot analysis is one
      technology that allows the measurement of relative levels of multiple mRNAs.
      However, potential problems exist with this approach, such as (i) unknown
      amplification efficiencies and sensitivity of detection, (ii) an inherent 3' bias
      of amplified products and (iii) cross-hybridization of homologous mRNAs with the
      gene targets. Each of these potential problems was addressed experimentally by
      the use of poly(A) RNA internal standards synthesized from lambda phage (lambda)
      DNA. The results showed detection levels of as few as 10 copies of the poly(A)
      RNA internal standards. The internal standards aid in the optimization of
      reaction conditions and also reduce dependence on traditional "housekeeping"
      genes whose mRNA levels might or might not change. The overall results of these
      experiments highlight and extend the general usefulness of amplified antisense
      aRNA and reverse Northern blot analysis to study mRNA expression profiles.

PMID- 9762446
TI  - Selective propagation of retinal pericytes in mixed microvascular cell cultures
      using L-leucine-methyl ester.
AB  - Endothelial cell (EC) propagation has been simplified by developing cell-specific
      selection criteria. Methods commonly used for selectively isolating EC include:
      (i) differential sieving of disaggregated tissue, (ii) differential plating of
      cells on extracellular matrices, (iii) lectin affinity isolation of cell
      populations and (iv) fluorescence-activated cell sorting of cells labeled with a
      carbocyanine dye of acetylated low-density lipoprotein (DiI-Ac-LDL). Few criteria
      for selectively propagating pericytes (PC) are currently available. Nonspecific
      esterases exhibit a high degree of multiplicity when compared with other
      mammalian isozymes and may be suitable for the identification and selective
      propagation of cells of the microvasculature. Evaluation of esterase isotype
      expression in PC and EC by zymography indicates PC contain alpha-naphthyl acetate
      and alpha-naphthyl butyrate hydrolyzing esterases as well as dipeptidyl peptidase
      I, while EC only contain alpha-naphthyl acetate esterase. The cytotoxic response
      of PC and EC to various amino acid esters is assessed by monitoring vital dye
      uptake and by light microscopy. Several amino acid esters are cytotoxic to both
      cell types, whereas 50 mM L-leucine methyl ester (L-Leu OMe) is toxic to EC but
      not to PC. This amino acid ester is also toxic to mesothelial and retinal
      pigmented epithelial cells, other common contaminants of PC cultures. Analysis of
      protein composition by two-dimensional gel electrophoresis indicates that L-Leu
      OMe does not stimulate expression of stress response proteins in PC. Thus, L-Leu
      OMe can be utilized to cultivate PC selectively from mixed cell populations.

PMID- 9762449
TI  - Mutation typing using electrophoresis and gel-immobilized Acrydite probes.
AB  - A new electrophoresis technology for hybridization-based sequence detection and
      mutation typing is described. Intrinsic to this approach is copolymerization of
      specially modified oligonucleotide probes directly into polyacrylamide gels.
      Electrophoresis of single-stranded samples through gels containing specific
      immobilized probes results in hybridization-mediated capture of complementary
      targets. By increasing gel temperature or including denaturants in the buffer,
      the method can be used to type single-nucleotide polymorphisms. The method can
      easily be adapted to type mutations in PCR-amplified samples. Acrydite gel
      technology will also be useful for many other applications, including
      hybridization-based diagnostics, analysis of gene expression and purification of
      nucleic acids from biological samples.

PMID- 9762450
TI  - Measurement of isolated myocyte volume using the Coulter models Z2 and ZM/C256: a
      comparison of instrument function.
AB  - Changes in cardiac structure that depart from normal have generally been termed
      "remodeling". Assessment of ventricular remodeling at the cellular level should
      include measurement of myocyte dimensions. A well-established and reliable method
      to assess myocyte remodeling uses isolated cells and the Coulter
      Counter/Channelyzer system. The new Coulter Model Z2 has numerous modifications
      and improvements from the Model Z predecessor(s) interfaced to a pulse-height
      analyzer (e.g., channelyzer). Improvements of the Model Z2 over older instruments
      include: (i) elimination of the mercury manometer with accompanying oil
      displacement pump; (ii) reduced size and weight; (iii) a higher degree of
      mechanization and automation; (iv) inclusion of an advanced comprehensive
      statistical package and (v) a substantial reduction in cost. The purpose of this
      study was to determine if the newly modified instrument produces the same results
      as the previous instrument combinations, which were shown to produce reliable
      cell volume data from irregularly shaped cells such as cardiac myocytes.

PMID- 9762451
TI  - Aetiology of oral cancer: alcohol.
AB  - The effect of alcohol alone on the oral mucosa and its association with the
      development of oral cancer is difficult to establish, principally because alcohol
      consumption histories are difficult to verify, alter over time, both with respect
      to beverage type and quantity, and are frequently confounded by tobacco use. This
      review considers the various pathways by which alcohol may exert such an
      influence. Namely, due to topical exposure (e.g. direct effect on cell membranes,
      altered cell permeability, variation in enzymes that metabolise alcohol) and/or
      systemic effects (e.g. nutritional deficiency, immunological deficiency,
      disturbed liver function). Finally, the numerous papers that have sought to
      establish the relative risk for oral cancer in association with alcohol intake
      are reviewed.

PMID- 9762452
TI  - Proliferative activity and loss of function of tumour suppressor genes as
      'biomarkers' in diagnosis and prognosis of benign and preneoplastic oral lesions
      and oral squamous cell carcinoma.
AB  - Oral cancer is a disease of the elderly and is closely connected with cigarette
      smoking and alcohol consumption. Since the successful introduction of
      multidisciplinary treatment, the survival rate has not changed. Because of the
      high mortality and potentially disfiguring treatment, today's efforts are aimed
      at eliminating risk factors, chemoprophylaxis, improvement in diagnostic
      procedures, and understanding of the genetic mechanisms of oral carcinogenesis.
      Immunohistochemical and molecular biology analysis of biopsy tissue and cell
      lines of preneoplastic and neoplastic lesions that originate from the oral mucosa
      have shown that alterations in tumour suppressor genes such as p53 and Rb gene
      may have an important role in oral carcinogenesis and may be potentially useful
      prognostic 'biomarkers' in oral carcinogenesis. Statistical analysis of
      immunohistochemical data from 216 patients did not identify significant or
      consistent differences of p53, MDM2, or RB expression with respect to stage of
      disease, malignant transformation, metastatic node involvement, recurrence, or
      survival. Nevertheless, p53 overexpression seems to correlate strongly with
      histological progression of the disease, which confirms the importance of p53
      alterations in oral carcinogenesis. Overexpression of p53 is usually found in the
      less differentiated proliferating cells in benign and malignant oral lesions.
      Assessment of the proliferating activity is possible by immunohistochemical
      staining with monoclonal antibodies against proliferating nuclear antigen and Ki
      67. Statistical analysis shows that overexpression of p53 combined with high
      proliferative activity predicts a less favourable course of disease in oral
      squamous cell carcinoma.

PMID- 9762453
TI  - Orthognathic surgery: the patients' perspective.
AB  - It is often thought that patients seek combined orthodontic and surgical
      treatment for predominantly aesthetic reasons, with functional concerns being
      secondary. To find out whether patients were more satisfied with appearance than
      function after treatment, all 165 patients who had orthognathic operations during
      the 11-year period 1983-94 were sent a questionnaire; 139 responded (84%). Rating
      on a visual analogue scale showed a high level of satisfaction for both
      appearance (mean score 6.78) and function (mean score 7.24) (Wilcoxon test, P =
      0.046). This indicates that orthognathic surgery is not merely done for aesthetic
      reasons, but is important when combined with orthodontic treatment in correcting
      severe malocclusions, which appreciably improve the ability to chew.

PMID- 9762454
TI  - Fibrous dysplasia of the craniomaxillofacial region: current clinical
      perspectives.
AB  - Fibrous dysplasia is a benign fibro-osseous disease of bone of unknown etiology.
      Its occurrence in the craniomaxillofacial skeleton is frequent and varies in
      severity from an asymptomatic monostotic lesion to polyostotic involvement
      resulting in progressive functional deficit and aesthetic problems. With the
      advent of refined instrumentation and craniofacial surgical techniques, a more
      aggressive, non-disabling approach to these benign yet deforming fibro-osseous
      growths is possible. In some patients, complete excision of the involved bone
      with graft reconstruction of the resultant defect with primary autogenous bone
      may be possible. Lifelong continuous ongoing monitoring of the involved region is
      required throughout the patient's life.

PMID- 9762455
TI  - The use of computer-generated three-dimensional models in orbital reconstruction.
AB  - In this paper we describe the application of three-dimensional (3D) imaging and
      computer-generated models in the management of orbital deformity. The technique
      was found to be particularly useful in posttraumatic deformity and fibrous
      dysplasia involving the orbit. Further application was found in cases of
      radiation hypoplasia, high facial cleft, and facial atrophy. Funding restrictions
      necessitate appropriate selection of cases when using new and expensive 3D
      imaging rather than traditional and less expensive methods. To remain within a
      realistic budget only those patients who will clearly benefit from the third
      dimension compared with traditional methods of assessment and management should
      be selected. These include patients requiring precise reduction or secondary
      reconstruction in which there is a matched normal anatomical component for
      comparison. This application is also only beneficial where the planned
      reconstruction is dimensionally stable.

PMID- 9762456
TI  - Vascularity of the dental pulp after segmental osteotomy in the chacma baboon
      (Papio ursinus).
AB  - OBJECTIVE: To assess the vascularity of the dental pulp after segmental
      operations with and without interpositional autogenous bone grafting. DESIGN:
      Experimental study. SETTING: University Department, South Africa. ANIMALS: 26
      chacma baboons. INTERVENTIONS: Maxillary and mandibular posterior segmental
      osteotomies were perfused with barium sulphate 3, 6, 12 and 18 months
      postoperatively. The animals were killed at 3, 6, 12 and 18 months after surgery
      and perfused with barium sulphate. Barium-filled vessels were counted in
      histological sections from 189 control and experimental teeth. MAIN OUTCOME
      MEASURE: Number of blood vessels. RESULTS: Blood vessel counts in mandibular
      teeth in osteotomy segments ranged from 0 to 1.15 compared with 2.27 to 4.58 in
      control teeth, while in maxillary teeth counts ranged from 0.54 to 2.22 for
      experimental teeth and 3.3 to 4.65 for controls. For both jaws, the numbers of
      vessels in experimental teeth gradually increased between 3 and 18 months but
      remained less than those in control teeth. Numbers of blood vessels were similar
      in graft and no-graft groups but both were less than half the counts in control
      teeth. CONCLUSION: Blood flow is present in the teeth at all times after
      posterior segmental osteotomy but there is a risk of ischaemia.

PMID- 9762457
TI  - Reconstruction of the extremely resorbed mandible with interposed bone grafts and
      placement of endosseous implants. A preliminary report on outcome of treatment
      and patients' satisfaction.
AB  - During recent decades many surgical techniques have been developed to enlarge the
      denture-bearing area of the mandible. Most of these techniques improved retention
      and stability of the lower dentures only temporarily. Since the advent of
      endosseous implants to stabilize overdentures, combinations of augmentation
      procedures and placement of endosseous implants have been introduced to restore
      the severely resorbed mandible. In this study we describe the preliminary results
      of such a combined approach using sandwich osteotomy with an autogenous bone
      graft (iliac crest) followed by placement of four endosseous implants in the
      interforaminal region in 10 women. After a mean follow-up period of 31 months
      (range 19-57) several variables were measured including condition of the peri
      implant tissues, radiographic bone changes and patient satisfaction. The first
      results indicate that the technique described offers a solid base for implant
      stabilized overdentures: no implants were lost, the peri-implant tissues were in
      good condition, bone loss was limited, and patients were satisfied. Future
      studies will evaluate the permanence of these results.

PMID- 9762458
TI  - Treatment of the edentulous mandible with a vestibuloplasty combined with
      Intramobil Zylinder implants: a 5-year follow-up.
AB  - The long-term success of endosseous implants is related to healthy peri-implant
      tissues. Attached keratinized mucosa does not seem important for the prevention
      of soft tissue complications. Prevention of muscle attachment near the implants,
      however, seems more decisive for maintaining a favourable peri-implant
      environment. We treated 150 patients from 1990-91 with two Intramobil Zylinder
      implants and modified vestibuloplasty, 65 of whom were randomly selected for
      evaluation at 1 year; 48 of the 65 were also seen at 5 years. The vestibuloplasty
      was done by the technique of Pichler and Trauner, to prevent muscle pull and to
      create a thin layer of mucosa around the implants, and endosseous osseointegrated
      implants were inserted. The results show an adequately depended vestibulum with
      no muscle pull around the implants and significantly lower pocket depth after 5
      years of follow-up compared with similar studies.

PMID- 9762459
TI  - Immunocytochemistry of fine-needle aspirates from central giant cell granuloma.
AB  - Fine needle aspiration biopsy (FNAB) is an important technique in the diagnosis
      of oral and maxillofacial conditions. We describe here the cytological and
      immunocytological findings in four patients with central giant cell granuloma.
      All the aspirates showed mononuclear cells associated with many giant cells. We
      conclude that immunocytochemical examination of FNAB specimens helps to confirm
      the provisional clinical diagnosis of central giant cell granuloma.

PMID- 9762460
TI  - Diagnostic imaging in two cases of recurrent maxillary ameloblastoma: comparative
      evaluation of plain radiographs, CT and MR images.
AB  - We report detailed clinical and imaging findings of two patients with recurrent
      maxillary ameloblastoma. In one patient the recurrent tumour presented at follow
      up examination 5 years after the initial operation. The other patients had a far
      advanced recurrent tumour with maxillary destruction extending into the adjacent
      normal structures including the infratemporal fossa, infraorbital fissure,
      masticator space and the left ethmoid sinus. The findings on conventional
      radiography including panoramic, posteroanterior and Waters' projection, and the
      findings of computed tomography (CT) and magnetic resonance (MR) imaging were
      evaluated using the following three variables: artefact degradation, lesion
      detectability, and conspicuity. The results suggested that MR imaging was the
      best imaging method for visualization of the tumours, followed by contrast
      enhanced CT. These two cases show that maxillary ameloblastoma can be difficult
      to control when it extends to the adjacent normal structures after destroying the
      maxilla. MR imaging was essential to establish the exact extent of the advanced
      maxillary ameloblastoma.

PMID- 9762461
TI  - Cutaneous sinus tract of dental origin--imaging with a dental CT software
      programme.

PMID- 9762462
TI  - Synovial chondromatosis of the temporomandibular joint.

PMID- 9762463
TI  - Langerhans' cell histiocytosis.

PMID- 9762464
TI  - Re: Pratt et al. Controversies in third molar surgery: the national view on
      review strategy. Br J Oral Maxillofac Surg 1997; 35: 319-322.

PMID- 9762465
TI  - Pathological fracture of the mandible treated with diphosphonates.

PMID- 9762466
TI  - Microtubule depolymerization induces stress fibers, focal adhesions, and DNA
      synthesis via the GTP-binding protein Rho.
AB  - Microtubule depolymerization has multiple consequences that include actin stress
      fiber and focal adhesion assembly, increased tyrosine phosphorylation and DNA
      synthesis. Similar effects induced by serum, or agents such as lysophosphatidic
      acid, have previously been shown to be mediated by the GTP-binding protein Rho.
      We have investigated whether the effects of microtubule depolymerization are
      similarly mediated by Rho and show that they are blocked by the specific Rho
      inhibitor, C3 transferase. Because microtubule depolymerization induces these
      effects in quiescent cells, in which Rho is largely inactive, we conclude that
      microtubule depolymerization leads to activation of Rho. The activation of Rho in
      response to microtubule depolymerization and the consequent stimulation of
      contractility suggest a mechanism by which microtubules may regulate
      microfilament function in various motile phenomena. These range from growth cone
      extension to the development of the contractile ring during cytokinesis, in which
      there are interactions between the microtubule and microfilament systems.

PMID- 9762467
TI  - Localisation of a novel adhesion blocking epitope on the human beta 1 integrin
      chain.
AB  - Members of the beta 1 integrin family mediate cellular adherence to a wide range
      of extracellular and cell surface associated ligands. Conformational changes have
      been shown to be associated with integrin activation and ligand binding. Some
      studies suggest that there may be a restricted region of the beta 1 integrin that
      serves as the target for regulatory antibodies which can inhibit or stimulate
      integrin function. Here we identify an inhibitory epitope that is located at a
      distinct sight from that suggested for other inhibitory antibodies. Three
      different adhesion blocking antibodies, JB1A, C30B, and D11B bind to a peptide
      corresponding to residues 82-87 of the mature beta 1 chain. Mn++ inhibited the
      binding of JB1A to purified beta 1 integrin. In contrast the binding of several
      other antibodies to beta 1 were not influenced by these conditions. JB1A binding
      to purified peptide was also inhibited by Mn++ suggesting that it related to
      interference with the antibody function rather than a cation dependent change in
      the epitope. Our data 1) directly demonstrates the peptide sequence recognised by
      three adhesion blocking antibodies to the human beta 1 integrin chain 2)
      identifies a novel epitope located at residues 82-87, distinct from that of
      previously described regulatory epitopes 3) characterises a Mn++ sensitive
      antibody integrin interaction. Collectively, these results indicate the existence
      of multiple regulatory sites on the beta 1 integrin molecule.

PMID- 9762468
TI  - Binding of the alpha 2 integrin I domain to extracellular matrix ligands:
      structural and mechanistic differences between collagen and laminin binding.
AB  - The alpha 2 beta 1 integrin functions as a cell surface receptor for collagen on
      some cells and as both a collagen and laminin receptor on a more restricted
      subset of cell types including endothelial and epithelial cells. The alpha 2
      integrin subunit I domain binds collagen in a divalent cation-dependent manner.
      In contrast, I domain binding to laminin occurs via both divalent cation
      dependent and -independent mechanisms. Saturable binding was observed in the
      presence of either Mn2+ or EDTA, although the extent of binding in Mn2+ was twice
      that observed in EDTA. Half-maximal binding occurred at about 22 nM I domain in
      either case. Whereas laminin binding was significantly enhanced by Mn2+, with
      half-maximal binding occurring at 1.9 mM Mn2+, Mg2+ was much less effective.
      Deletion of the N-terminal 35 residues of the I domain, including the DXSXS
      portion of the MIDAS motif, caused a significant diminution of laminin binding
      activity. Laminin binding by the I domain was significantly inhibited by the
      alpha 2 beta 1 function-blocking antibody 6F1 in the presence of either EDTA or
      Mn2+. The non-function-blocking antibody 12F1 had no effect. In contrast to the
      binding of the alpha 2 integrin I domain to collagen, the laminin binding
      activity of the I domain was not enhanced by the addition of the first EF hand
      motif of the integrin.

PMID- 9762469
TI  - A mutation in alpha-catenin disrupts adhesion in clone A cells without perturbing
      its actin and beta-catenin binding activity.
AB  - Cadherin mediated cell-cell adhesion requires cytoplasmic connections to the
      cytoskeleton mediated by alpha-catenin. Original descriptions of the catenins, as
      well as our own in vitro studies, have suggested that this connection was
      mediated by the interaction of alpha-catenin to actin. Loss of adhesion in the
      human colon carcinoma cell line "Clone A" is the result of an internal deletion
      mutation of 158 residues near the N-terminus of the protein resulting in an 80 kD
      mutated protein. Transfection of these cells with the full length protein
      restores the normal adhesive phenotype. We have characterized this mutant protein
      in efforts to understand the normal function of alpha-catenin and, in particular,
      the region deleted in the Clone A mutant. Co-precipitation experiments using
      whole cell lysates indicate that the mutant form of alpha-catenin binds beta
      catenin and plakoglobin, and can form a structural complex with E-cadherin via
      these interactions. Actin co-sedimentation assays show that the recombinant
      mutant binds and bundles F-actin and binds both actin and beta-catenin
      simultaneously, as seen with wild type alpha-catenin. These results suggest that
      the stabilization of the E-cadherin-catenin complex may be mediated by factors
      beyond its direct interaction with actin. We conclude that a region near the N
      terminus of alpha-catenin mediates additional interactions between the adhesive
      complex and the cytoskeleton that are critical for functional adhesion.

PMID- 9762470
TI  - Protein phosphatase 1 delta is associated with focal adhesions.
AB  - In all mammalian cells protein phosphatase-1 (PP1) exists in three isoforms,
      defined as alpha, gamma 1 and delta. Immunofluorescence studies with isoform
      specific antibodies indicated that delta, but not alpha or gamma 1, is enriched
      at focal adhesions in HeLa cells, fibroblasts, endothelial cells and
      keratinocytes. This was confirmed also by interference reflection microscopy,
      which indicated that PP1 delta was in areas of tight adhesion of the membrane to
      the extracellular matrix at sites where the microfilament cytoskeleton is
      organized. In all the cell types so far considered the PP1 delta in focal
      adhesions represented only a small aliquot of the total PP1 delta, which was
      predominantly localized to the nucleus. The association of PP1 delta to focal
      adhesions was confirmed by the co-immunoprecipitation of PP1 delta with the focal
      adhesion kinase pp125FAK and with the alpha v integrin. Comparison between the
      amount of PP1 delta associated with focal adhesion proteins and that of PP1 delta
      recovered in an anti-PP1 delta immunoprecipitate confirmed that only a minor
      amount of the enzyme was associated with the focal adhesions. Since some focal
      adhesion proteins are phosphorylated on Ser/Thr, it is likely that PP1 delta may
      be involved in the regulation of focal adhesion functions and particularly in the
      signaling pathway generated by cell-substratum adhesion.

PMID- 9762471
TI  - Adhesive interactions of human multiple myeloma cell lines with different
      extracellular matrix molecules.
AB  - Multiple myeloma represents a human B cell malignancy which is characterized by a
      predominant localization of the malignant cell clone within the bone marrow. With
      the exception of the terminal stage of the disease the myeloma tumor cells do not
      circulate in the peripheral blood. The bone marrow microenvironment is believed
      to play an important role in homing, proliferation and terminal differentiation
      of myeloma cells. Here we have studied the expression of several extracellular
      matrix (ECM) molecules in the bone marrow of multiple myeloma patients and
      analyzed their adhesive capacities with four different human myeloma-derived cell
      lines. All ECM molecules analyzed (tenascin, laminin, fibronectin, collagen types
      I, III, V and VI) could be detected in bone marrow cryostat sections of multiple
      myeloma patients. Adhesion assays showed that only laminin, the microfibrillar
      collagen type VI and fibronectin were strong adhesive components for the myeloma
      cell lines U266, IM-9, OPM-2 and NCI-H929. Tenascin and collagen type I were only
      weak adhesive substrates for these myeloma cells. Adhesion to laminin and
      fibronectin was beta 1-integrin-mediated since addition of anti-beta 1-integrin
      antibodies could inhibit the binding of the four different cell types to both
      matrix molecules. In contrast, integrins do not seem to be involved in binding of
      the myeloma cells to collagen type VI. Instead, inhibition of binding by heparin
      suggested that membrane-bound heparan sulfate proteoglycans are responsible
      ligands for binding to collagen type VI. Adhesion assays with several B-cell
      lines resembling earlier differentiation stages revealed only weak interactions
      with tenascin and no interactions with collagen type VI, laminin or fibronectin.
      In summary, the interactions of human myeloma cells with the extracellular matrix
      may explain the specific retention of the plasma cells within the bone marrow.

PMID- 9762472
TI  - Expression profile of vascular cell adhesion molecule-1 (CD106) in inflammatory
      foci using rhenium-188 labelled monoclonal antibody in mice.
AB  - Rhenium (Re)-188 is a generator (W-188/Re-188) produced high energy beta-emitter
      suitable for radionuclide therapy (T1/2 is 16.9 hrs and Emax 2.1 MeV (range 11
      mm)). We have labelled monoclonal antibody (MAb) raised against vascular cell
      adhesion molecule-1 (VCAM-1) with Re-188 using glucoheptonate chelation technique
      and SnCl2 as reducing agent. The labelling efficiency, free perrhenate and
      reduced Re were controlled with thin layer chromatography and the purification of
      Re-188-MoAbs was performed using gel filtration. Our results indicate that Re-188
      labelled antibodies remain in vitro stable and the labelling purity is > 90%. We
      also have applied these Re-188-MoAbs for detection of inflammatory disease in a
      mouse. The effective half-lives of organs of interest after an injection of Re
      188-anti-VCAM1 were as follows: blood 5.2 hr, kidney 4.7 hr, and liver 9.6 hr. Re
      188-anti-VCAM-1 was found to accumulate mainly in kidney and liver. One hour
      after the injection, the kidney contained in average as high as 12.5% and the
      liver 2.8 ID/g tissue. After 6 hr, the kidney contained 5.5% ID/g and the liver
      2.6% ID/g. At 24 hr, the kidney uptake was 0.5% ID/g and the liver uptake 0.8%
      ID/g, respectively. The inflamed foci, subcutaneous lesions in the footpad skin,
      were visualized using gamma camera. From the distribution data the uptakes in the
      inflamed foci as follows: at 1 hr 2.18 (inflammation) and 1.72% ID/g (control),
      at 6 hr 1.42 (inflammation) and 0.85% ID/g (control), and at 24 hr 0.17
      (inflammation) and 0.084% ID/g (control), respectively. Anti-VCAM-1 MAb showed
      better targeting as compared to control MoAbs in inflammation (caused by E.coli
      lipoplysaccaride). In conclusion, Re-188 is suitable for MAb labelling, and MAb
      against VCAM-1 may be used for detection of local inflammatory disease.

PMID- 9762473
TI  - Tendinopathy: an Achilles' heel for athletes and clinicians.

PMID- 9762474
TI  - Long-term restoration of deficits in bone mineral density is inadequate in
      premenopausal women with prior menstrual irregularity.
AB  - OBJECTIVE: To investigate change in bone mineral density (BMD) in premenopausal
      women (age, 29-46 years), some of whom were marathon runners with a history of
      menstrual irregularity. DESIGN: Longitudinal follow-up. SETTING: University
      medical school. PARTICIPANTS: We investigated 8 sedentary controls (SC) and 19
      marathon runners (12 with regular menses (R) and 7 with a history of irregularity
      (OA) 11.7 +/- 7.9 years before follow-up). MAIN OUTCOME MEASURES: BMD (g/cm2) of
      lumbar spine (LS) and proximal femur were determined at baseline and follow-up (3
      5 years later). We calculated a menstrual history index (MHI) (estimated
      periods/year since age 13). RESULTS: Body mass, age at menarche, and femoral BMD
      were not statistically different. Follow-up LS BMD (g/cm2) was lower (p < 0.01)
      in OA (0.936 +/- 0.060) than in R (1.043 +/- 0.103) and SC (1.094 +/- 0.077),
      even when covarying for age or both age and mass. No group changed BMD
      significantly with time. Current MHI was lower (p < 0.001) in OA (9.7 +/- 1.4)
      than in R (11.3 +/- 0.5) and SC (11.8 +/- 0.4). MHI for the teenage years was
      lower in OA than in SC but not in R. OA had significantly lower MHI than did R
      and SC for the third and fourth decades. Only MHI during the third decade
      correlated significantly with LS BMD for all subjects. CONCLUSIONS: Restoration
      of LS BMD deficit in women with prior menstrual irregularity aged over 30 is slow
      and may never reach the same level as age-related controls; secondly, this may be
      the result of both bone loss in the third decade of life and reduced acquisition
      during adolescence.

PMID- 9762475
TI  - Development, implementation, and validation of the Canadian Intercollegiate Sport
      Injury Registry.
AB  - PURPOSE: To outline the development and implementation of the Canadian
      Intercollegiate Sport Injury Registry (CISIR), to examine its validity, including
      the data collection forms, the recording of athlete exposure, and the mechanism
      of injury, and to determine the ability of the CISIR to meet its stated
      objectives of assessing rates and risk of injury. DESIGN: Prospective cohort
      study. SETTING: Canadian intercollegiate athletics. SUBJECTS: 344 varsity
      football players from five western Canadian universities. ASSESSMENT OF RISK
      FACTORS AND OUTCOME MEASURES: Three data collection instruments were developed to
      capture the principle types of information forming the cornerstones of the CISIR:
      a medical form for preseason assessment of risk factors, a weekly exposure sheet
      (WES) for the documentation of daily individual athlete participation, and an
      individual injury report form (IIRF) for collection of injury-related
      information. Design and implementation input was provided by therapists and
      physicians through initial meetings, pilot testing, site visits, questionnaire,
      and final consensus meeting. The completeness of injury reporting was assessed
      through cross-referencing with participation time loss data. An item analysis was
      conducted on the principal elements of the IIRF. The categorization of
      participation itself was also examined, as was the diagnostic agreement between
      the therapists and physicians involved in data collection. The recorded mechanism
      of injury was compared with that noted through a video analysis for game-related
      injuries. Lastly, a test analysis was conducted to extract data and compute rates
      and risks of injury. RESULTS: This developmental phase was successful, with 99.7%
      subject enrollment, high therapist satisfaction, and good flow of data. A
      relational database, incorporating dual-entry data verification, was designed and
      functioned well. The collection process revealed that 100% of the WESs were
      submitted, and the data therein was 99.7% complete. The injuries resulting in
      participation time loss were recorded on an IIRF 97.9% of the time. The exposure
      (participation) codes were thought to be overly precise, and a simplification of
      these categories is suggested. The diagnostic agreement between physicians and
      therapists was 70%. It was possible to validate game exposures, but no standard
      was identified to permit validation of the categories of exposure. Likewise, the
      mechanism of injury as recorded by the therapists was thought to be more precise
      than the video analysis. After two modifications in the table structure of the
      relational database, it was possible to extract data relating to rates and risks
      of injury. CONCLUSIONS: This study demonstrated a high degree of validity for
      many elements of the CISIR. One limitation was that no reference standard existed
      for some components, limiting some aspects of validity assessment. With the
      suggested revisions, the CISIR represents the current standard in athletic injury
      reporting in terms of individual injury risk assessment. This system will be used
      in the future to explore the prediction and prevention of sport injuries.

PMID- 9762476
TI  - Hormonal responses to endurance training and overtraining in female athletes.
AB  - OBJECTIVE: To examine different hormonal responses to heavy endurance training
      and overtraining in female athletes. DESIGN: Submaximal and maximal treadmill
      tests, self-report mood measures, and stress hormone analyses were repeated at
      baseline, after 4 weeks and at the end of 6 to 9 weeks of experimental intensive
      training and after 4 to 6 weeks of recovery. SUBJECTS: Fifteen healthy female
      endurance athletes increased their intensive training volume by 130% and base
      training volume by 100% (ETG, n = 9) or served as controls (CG, n = 6). MAIN
      OUTCOME MEASURES: Maximal oxygen uptake (VO2max), mood dynamics, blood
      catecholamines, cortisol and testosterone at rest and after submaximal and
      maximal exercise, and nocturnal urine catecholamines. RESULTS: Five females from
      the ETG demonstrated an over-training state (OA subgroup) at the end of the
      training period. Their VO2max decreased (mean +/- SEM) from 53.0 +/- 2.2 ml.kg
      1.min-1 (range, 46.8-59.2) to 50.2 +/- 2.3 ml.kg-1.min-1 (range, 43.8-56.6) (p <
      0.01). Maximal treadmill performance expressed as oxygen demand decreased (mean
      +/- SEM) from 56.0 +/- 1.6 ml.kg-1.min-1 (range, 51.5-60.5) to 52.2 +/- 1.1 ml kg
      1.min-1 (range, 49.1-55.3) (p < 0.01). Maximal heart rate also decreased (mean +/
      SEM) from 190 +/- 1 bpm (range, 185-197) to 186 +/- 2 bpm (range, 184-193) (p <
      0.05), and the athletes experienced mood disturbances. Plasma adrenaline levels
      at maximal and noradrenaline at submaximal work rate decreased during the last 2
      to 5 training weeks (p < 0.05), and serum cortisol levels at maximal work rate
      decreased during the first 4 training weeks (p < 0.05) in the ETG. Plasma
      adrenaline at maximal work rate decreased during the first 4 training weeks (p <
      0.05) in the OA subgroup. There were no changes in the CG. Individual hormonal
      response types to heavy training and overtraining were found. CONCLUSIONS:
      Hormone responses to exercise load are superior in indicating heavy training
      induced stress when compared with resting hormone levels. These responses
      indicated decreased sympathoadrenal and/or adrenocortical activity (or exhaustion
      of the adrenal gland or the central nervous system). Individual hormonal profiles
      are needed to follow up training effects. Marked individual differences were
      found in training- and overtraining-induced hormonal changes.

PMID- 9762477
TI  - Injuries in runners: a prospective study of alignment.
AB  - OBJECTIVE: To determine if measurable lower extremity alignment is a risk factor
      for overuse running injuries. DESIGN: Prospective cohort study. SETTING: Thirty
      two week marathon training program. PATIENTS OR PARTICIPANTS: Three hundred fifty
      five volunteers from the marathon training program began the study; 255 finished
      the study. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Past training and injury
      history was determined by questionnaire, and five lower extremity alignment
      measures were performed at the beginning of the training program: arch index
      (AI), heel valgus (HV), knee tubercle-sulcus angle (TSA), knee varus (KV), and
      leg-length difference (LLD). Overuse injuries, incurred by the runners and
      categorized by anatomic parts, were recorded during the training period. RESULTS:
      Ninety subjects experienced overuse injuries. Multivariate analyses with stepwise
      Poisson regression showed few consistent relationships between alignment and
      overuse injury rates. Higher AI was protective against overall injuries and knee
      injuries; higher HV was protective against knee and foot injuries; higher TSA was
      associated with shin injuries; higher KV was associated with shin injuries; and
      low LLD was associated with more overall injuries. CONCLUSIONS: Minor variations
      in lower extremity alignment do not appear conclusively to be major risk factors
      for overuse injuries in runners. Because of the study limitations and the likely
      multifactorial nature of running injuries, further study is suggested, perhaps in
      more novice runners.

PMID- 9762478
TI  - Discordant public perception of doping in elite versus recreational sport in
      Switzerland.
AB  - OBJECTIVE: To assess public awareness of performance-enhancing drug use, that is,
      doping in sport in Switzerland. DESIGN: Representative telephone survey in
      September 1995. SETTING: Two of the three Swiss linguistic areas (French and
      German), representing 96% of the entire Swiss population. SUBJECTS: A total of
      1201 respondents between 18 to 74 years old, selected by stratified random
      sampling. MAIN OUTCOME MEASURES: Perception of the doping problem in elite versus
      recreational sport, estimated prevalence of doping in different sports, parents'
      decisions to keep children out of sport because of doping. RESULTS: The use of
      doping in sport was perceived as a "somewhat serious problem" or "very serious
      problem" by 84% of the respondents for elite sport and by 44% for recreational
      sport (p < 0.01 for difference). Doping was mostly perceived to represent a
      physical health problem or an ethical problem. Track and field (79%) and cycling
      (27%) were most often cited as sports having doping problems, and 35% of the
      respondents believed that > 60% of bodybuilders use doping. The black market
      (91%), athletes and trainers (80%), and fitness centers (74%) were the most
      frequently mentioned sources of doping substances. Thirteen of 14 parents would
      not dissuade their children from participating in sport because of a concern
      about the problems of doping. CONCLUSIONS: The Swiss population perceives a high
      prevalence of doping in sports. There is a clear distinction, however, made by
      the respondents between the estimated prevalence of doping in elite sport, seen
      overwhelmingly as a "very serious problem" or "somewhat serious problem," and
      recreational sport, in which doping is less often seen as a problem. Doping is
      considered a serious threat to health and ethics in sport, but despite this
      judgment, only a few parents would hold back their children from sport because of
      the risks of doping.

PMID- 9762479
TI  - Two measures of physical activity as predictors of bone mass in a young cohort.
AB  - OBJECTIVE: To compare the association of two measures of physical activity with
      bone mass in healthy children and young adults, as part of a larger study on bone
      mineral acquisition in youth. DESIGN: Cross-sectional observation study. SETTING:
      General community, outpatient study. PARTICIPANTS: Subjects included 103 non
      Hispanic white female (n = 54) and male (n = 49) healthy volunteers aged 9 to 25
      years. MAIN OUTCOME MEASURES: Self-reported physical activity was measured by a 3
      day activity diary of all activities and a questionnaire designed to capture
      recreational activities throughout the year. Activity was expressed as hours per
      week of weight-bearing and non-weight-bearing activity. Bone mass at the hip,
      spine, and whole body was measured by dual x-ray absorptiometry. RESULTS: The
      activity measures were not well correlated with each other. In males, weight
      bearing and non-weight-bearing activity reported in 3-day diaries was positively
      associated with bone mass at the hip, spine, and whole body (p < 0.05). Among
      females, only weight-bearing activity measured by the yearly questionnaires was
      significantly positively associated with bone mass (p < 0.05). In males and
      females, weight-bearing activity was more highly correlated with bone mineral
      than was non-weight-bearing activity. In addition, the associations between
      activity and bone mass varied by skeletal site. CONCLUSIONS: The association
      between physical activity and bone mass varied both in direction and in
      significance depending on the physical activity instrument used. Gender
      differences were observed in the associations between specific activity
      instruments, type of activity (weight-bearing and non-weight-bearing), and bone
      mass at different skeletal sites. Variability associated with the two physical
      activity measures may contribute to discrepant findings in this study and in the
      literature.

PMID- 9762480
TI  - Prospective evaluation of history and physical examination: variables to
      determine radiography in acute ankle injuries.
AB  - OBJECTIVE: This study investigated history and physical findings among 74
      patients with acute ankle injuries in order to determine factors significantly
      associated with fractures, excluding avulsion fragments < 3 mm in size, and
      syndesmosis injuries and to determine factors that necessitate radiography.
      DESIGN: This was a prospective study performed during a 12-month period. After
      recording history and physical examination data, a gestalt prediction of a
      positive or negative radiographic result was made before the patient underwent
      ankle radiography. Analysis then determined factors important for radiography.
      PATIENTS AND SETTING: Patients who presented to a sports medicine center with an
      acute ankle injury were enrolled in the study after meeting the enrollment
      criteria. MAIN OUTCOME MEASURES: Before analysis, predictions for injury were
      based on accepted indicators. Outcome measures, factors that would indicate the
      need for radiography, were formulated after data collection and statistical
      analysis. RESULTS: Radiographic findings showed nine fractures and three widened
      syndesmoses as well as 15 minor ligamentous avulsions. Statistical analysis
      showed significant association (p < 0.05) of fracture with previous ankle
      fracture, syndesmosis pain with external rotation stress testing, and pain along
      the middle third of the distal fibula, from anterior to posterior. Syndesmosis
      injuries had a significant association with pain during external rotation stress
      testing. CONCLUSIONS: Although additional investigation with larger patient
      numbers would be beneficial, this study highlights the importance of history of
      previous fracture, pain on the distal mid-fibula or mid-tibia, and pain with
      external rotation. Furthermore, if these three variables are prospectively
      applied as criteria for radiography, a 55% reduction in radiography would result
      with 100% sensitivity. Finally, experienced sports medicine physicians had a 100%
      sensitivity, 68% specificity, 100% negative predictive value, and 39% positive
      predictive value for prediction of clinically significant fractures or
      syndesmosis injuries.

PMID- 9762481
TI  - Electromyographic investigation of stretching: the effect of warm-up.
AB  - OBJECTIVE: To compare the fine wire electromyographic (EMG) firing patterns
      during static stretches in the biceps femoris, soleus, and gastrocnemius before
      and after warm-up as well as over time. DESIGN: Experimental single group pretest
      posttest design. SETTING: Biomechanics research laboratory. PARTICIPANTS: Sixteen
      healthy volunteers 23 to 36 years of age with no history of lower extremity
      injury. INTERVENTION: Subjects performed one hamstring stretch and four calf
      stretches for 90 seconds, bicycled for 30 minutes as a warm-up, and stretched
      again. MAIN OUTCOME MEASURE: EMG was recorded at time 0, 30, 60, and 90 seconds
      during the stretches before and after warm-up. Recorded values were normalized to
      EMG during maximum manual muscle testing (MMT). A two-way analysis of variance
      with repeated measures (p < 0.05) was done to compare EMG activity during
      stretching before and after warm-up as well as over time. RESULTS: Low EMG
      activity was seen for all muscles (< 20% MMT). It was constant over the time of
      the stretch for all muscles, but it increased in the soleus during the bent knee
      stretch position. There was a statistically significant decrease in the EMG
      activity after the warm-up for the gastrocnemius using the traditional and heel
      off stretching positions and for the soleus using the heel off stretching
      position (p < 0.05). The biceps femoris EMG activity showed no significant
      differences before and after warm-up. CONCLUSIONS: EMG activity during static
      stretching was low. Overall, the EMG activity remained constant with time for a
      given stretch position. EMG of the soleus and gastrocnemius was significantly
      less after warm-up for some stretches, whereas the EMG activity of biceps femoris
      showed no differences before and after warm-up.

PMID- 9762482
TI  - The effect of a needle biopsy of the vastus lateralis on isokinetic muscular
      performance.
AB  - OBJECTIVE: To determine the acute effects of a needle muscle biopsy of the vastus
      lateralis on knee extension and flexion strength and endurance. DESIGN: Pretest
      posttest design. Testing order of right or left leg was randomly determined.
      SETTING: Research Laboratory, University of Alberta, Edmonton Alberta, Canada.
      PARTICIPANTS: The subjects were 8 female and 11 male volunteers who were
      recreationally active. The mean age, height, and weight were 23 +/- 5 years,
      174.6 +/- 9.2 cm, and 73.5 +/- 7.3 kg, respectively. INTERVENTION: Isokinetic
      testing for knee extension and flexion was performed on both legs before and
      after a biopsy of the right vastus lateralis muscle. MAIN OUTCOME MEASURES: Knee
      extension and flexion peak torque measured at an angular velocity of 1.05 rad.s
      1. Mean torque during 25 consecutive maximal contractions at 3.14 rad.s-1 for
      knee extension and flexion exercise. RESULTS: There was a significant decrease in
      right knee extension peak torque after the biopsy of the vastus lateralis muscle.
      No other differences were noted. CONCLUSIONS: These findings demonstrated an
      acute inhibition of knee extension peak torque but not endurance because of a
      muscle biopsy of the involved musculature.

PMID- 9762484
TI  - Treatment of spondylolysis with external electrical stimulation and bracing in
      adolescent athletes: a report of two cases.

PMID- 9762483
TI  - How effective is exercise training for the treatment of hypertension?
AB  - OBJECTIVE: Exercise is often recommended as therapy for hypertension, yet its use
      is not widespread among clinicians. Reasons include uncertainty regarding its
      efficacy, the relative importance of the exercise prescription determinants
      (intensity and frequency), or confounding variables including patient
      characteristics such as age and gender. This review will present the evidence for
      exercise as a treatment for hypertension using a search of the English language
      literature from January 1966 to January 1998. DATA SOURCES: A search of MEDLINE
      articles using the MESH headings and textwords of blood pressure, hypertension,
      exercise, and exertion as well as hand searches in related articles and cross
      referencing. DATA EXTRACTION AND SYNTHESIS: Identified articles were reviewed for
      their design characteristics, and specific attention was made of the subject
      characteristics, the exercise training protocol, the magnitude of the blood
      pressure-lowering response, and the influence of pharmacologic treatment on blood
      pressure lowering. RESULTS: A total of 39 studies representing random and
      nonrandom designs using predominantly walking-jogging exercise were identified.
      These studies showed reductions in blood pressure (systolic blood
      pressure/diastolic blood pressure) of -13/ -18 mm Hg in hypertensive patients.
      Most of the antihypertensive effect of exercise training was observed after 10
      weeks, whereas training more than three times per week or for more than 50
      minutes did not confer added benefit. Lower intensity exercise resulted in
      greater blood pressure reduction than did high intensity exercise. No gender
      differences in the antihypertensive effect of exercise were observed although
      most studies were performed in men. Although few studies were performed in older
      patients, there did not appear to be an age-dependent antihypertensive effect of
      exercise. There was a paucity of literature regarding the interaction of
      pharmacologic therapy and exercise in hypertensive patients. CONCLUSIONS: The
      results support the use of exercise as an effective therapy in hypertension.
      Studies were generally lacking in adequate control groups. Future research
      opportunities are many and should include studies using ambulatory monitoring and
      stratification of patients with different degrees of hypertension, undergoing
      different pharmacologic regimens.

PMID- 9762485
TI  - Arachnoid cyst and subdural hygroma in a high school football player.

PMID- 9762486
TI  - Atlantoaxial dislocation in a sumo wrestler.

PMID- 9762487
TI  - Anomalous first rib in a high school wrestler.
AB  - A combination of noninvasive treatment modalities applied with basic
      biomechanical principles of motion was successful in treating an athlete with
      rare underlying skeletal anomalies. Back strains with recurrence or atypical
      findings require further workup. With such cervical rib anomalies, an athlete
      needs to be examined for thoracic outlet syndrome.

PMID- 9762488
TI  - Aminoglycoside ear drop ototoxicity: a topical dilemma?

PMID- 9762489
TI  - Frey's syndrome and parotid surgery.

PMID- 9762490
TI  - The treatment of hypertonicity of the pharyngo-oesophageal segment after
      laryngectomy.

PMID- 9762491
TI  - Suction diathermy adenoidectomy.
AB  - This technique uses a combination of monopolar diathermy and suction to perform a
      controlled resection of the adenoids in a near bloodless field. A clear view of
      the entire resection is obtained with a mirror. There is minimal blood loss and
      postoperative haemorrhage rate is extremely low. The authors describe the
      technique used and discuss their experience.

PMID- 9762492
TI  - The effectiveness of voice therapy for patients with non-organic dysphonia.
AB  - Forty-five patients diagnosed as having non-organic dysphonia were assigned in
      rotation to one of three groups. Patients in one group received no treatment and
      acted as a control group. Patients in the other two groups received a programme
      of either 'indirect' therapy or 'direct with indirect' therapy, respectively. A
      self-report questionnaire of vocal performance, observed ratings of voice
      quality, and computer-derived acoustic measurements (signal-to-noise ratio, pitch
      perturbation and amplitude perturbation) were carried out on all patients before
      and after treatment to evaluate the changes in voice quality over time. There was
      a significant difference between the three groups on the self-report
      questionnaire, voice quality ratings and pitch perturbation measurements (P = <
      0.05). Thirteen out of 15 control patients showed no significant change on any of
      the measures. Seven patients who received indirect treatment showed significant
      improvement in voice quality following treatment. Fourteen out of 15 patients who
      received direct treatment showed significant improvement in voice quality.

PMID- 9762493
TI  - Improved survival in patients with head and neck cancer in the 1990s.
AB  - It is generally felt amongst the medical profession and the lay public that
      cancer is being treated more successfully than in the past. This is certainly
      true for childhood malignancies and leukaemia but evidence that significantly
      improved survival is occurring in the common solid tumours is lacking. Since 1963
      the University of Liverpool Department of Otolaryngology/Head and Neck Surgery
      has collected data on all patients with head and neck tumours presenting to the
      department. The present study investigates patients with histologically proven
      squamous cell carcinoma of the four main sites: larynx, hypopharynx, oral cavity
      and oropharynx. From 1963 until the end of 1989, 2738 patients were seen by the
      department and from 1990 a further 717 patients have been seen. Since 1990
      patients have tended to be in better general physical condition but, on the other
      hand, have tended to have more advanced disease at the primary site. The
      department has latterly tended to see fewer laryngeal cancers and more cancers of
      the oropharynx. Significantly fewer patients have presented with neck node
      metastases. Multiple logistic regression suggests that the most significant
      difference between the two groups is the great reduction in neck node recurrence
      rates in the group of patients seen since 1990 (P = 0.0001). The recurrence of
      tumours at the primary site since 1990 has been 35% compared with 41% before
      1990, and recurrence in the neck nodes since 1990 has been 12%, compared with 15%
      before 1990. These differences are significant (P = 0.0141 and P = 0.0494,
      respectively). When studying survival in the 1960s, 1970s and 1980s, the 5-year
      cure rate was 50%, whereas since 1990 the figure has risen to 60% tumour-specific
      5-year survival--a significant difference. A similar effect was noted in observed
      survival. This improvement in cure rate occurred for all four main sites. The
      results were confirmed by Cox's proportional hazards model where year of
      treatment was highly significantly associated with improved survival (P =
      0.0001). It has been demonstrated that locoregional recurrence has improved since
      1990 and this is reflected in improved survival figures. Although there are
      differences in the parameters of tumours referred before 1990 and since 1990,
      multivariate analysis suggests that the improvement in neck node recurrence rates
      may be responsible for this improved survival rate. Multivariate analysis for
      survival also suggests that the improvement in cure rates is independent of
      compounding variables and dependent on the year of presentation of the tumour.
      This improved survival may be related to factors, such as the administration of
      radical postoperative radiotherapy.

PMID- 9762495
TI  - The contemporary practice of functional endoscopic sinus surgery: a nationwide
      survey.
AB  - Recent years have seen a rapid growth in the practice of functional endoscopic
      sinus surgery (FESS). Its introduction into clinical practice has, however, been
      conspicuous by an absence of good scientific evidence that it is superior to
      previous techniques. This postal questionnaire survey aimed to identify the
      diversity in the practice of FESS at a national level and, as a result,
      highlights areas of patient management requiring standardization. All full
      members of the British Association of Otolaryngologists--Head and Neck Surgeons
      (BAO-HNS) were contacted, 64% responded: 14% of surgeons do not always perform
      preoperative computerized tomography (CT) scanning; only 25% use grading systems
      for symptoms and/or CT assessment; a wide variety of topical agents are used both
      before and after operation; nearly half (47%) no longer operate principally under
      endoscopic vision but via TV monitors; and the majority of surgeons review
      patients more than 1 week after surgery with a minority advocating earlier
      postoperative assessment.

PMID- 9762494
TI  - The prevalence of exostoses in the external auditory meatus of surfers.
AB  - Fifty-four surfers and 38 surf life savers were examined and questioned in order
      to determine the prevalence of exostoses. Seventy-three per cent had evidence of
      body exostoses in the external auditory meatus. Forty per cent had their ear
      canals narrowed by 50% or more. The relationship between the number of years
      spent surfing or life saving and the extent of canal stenosis was highly
      significant (P < 0.00001). Left and right ears were affected equally in this
      series and the obstruction appears to begin after approximately 7 years and is
      further aggravated by continued surfing. Over 90% of subjects who had
      participated for longer than 10 years had some evidence of exostoses. There was
      no significant association between the number of days per year or the number of
      hours per day spent surfing and the development of surfer's ear in this sample.
      Those who participated in their water sport over winter had significantly more
      exostoses than those who did not (P < 0.0001). Those who lived in the South
      Island (colder water) had more surfer's ear than those in the North Island
      (warmer water).

PMID- 9762496
TI  - Structured assessment of the consequences of composite resection.
AB  - A structured quality of life questionnaire was developed as an instrument for the
      assessment of the functional, physical, psychosocial, and counselling problems in
      patients treated surgically for an oropharyngeal cancer. The questionnaire was
      tested in a pilot study in a relatively homogeneous group of 15 selected patients
      (all of whom had a comparable surgical defect, i.e. a composite resection of the
      oropharynx and neck, and had undergone an identical reconstruction method, i.e. a
      pedicled pectoralis major myocutaneous flap). All but two patients were
      irradiated as well. A high reliability (Crombach's alpha) was found in most of
      the applied subscales, indicating good internal consistency of the different
      questions. Significant correlations were found between several quality of life
      dimensions. The most frequently reported complaints concerned problems related to
      eating, speaking, and facial disfigurement. Problems with mastication, oral
      transport, and swallowing prohibited 11 patients returning to their normal diet.
      Regarding speech, 11 patients reported decreased intelligibility, in eight this
      was due to some degree of rhinolalia aperta. A significant association was found
      between moderate intelligibility and anxiety about speaking in public (P < 0.05).
      Eleven patients felt that the surgery had caused considerable facial
      disfigurement. For five of them this had a negative influence on their social
      interactions and activities outdoors. Thus, the consequences of the surgical
      treatment of oropharyngeal cancer can be assessed in a systematic and formal way
      with this specially designed structured questionnaire. Despite the small sample
      size, the selection of a homogeneous patient group appeared to give significant
      information, and to establish meaningful correlations.

PMID- 9762497
TI  - Matrix metalloproteinase-2 and matrix metalloproteinase-9 in cholesteatoma and
      deep meatal skin.
AB  - A qualitative and quantitative study of the presence of Matrix metalloproteinase
      2 (MMP-2) and Matrix metalloproteinase-9 (MMP-9) in cholesteatoma was performed.
      Ten cholesteatoma and four deep meatal skin specimens were analysed for
      gelatinase activity at molecular weights corresponding to MMP-2 and MMP-9 using
      Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis (SDS PAGE) Zymography.
      Gelatinase activity at 72 kDa and 92 kDa was investigated. Western blotting was
      employed using primary monoclonal antibodies to provide a qualitative assessment
      of MMP-2 and MMP-9. Non-parametric data analysis using the Mann-Whitney U test
      did not show a significant difference in expression of MMP-2 (P = 0.51) or MMP-9
      (P = 0.14) between the two tissue types. Western blotting showed the presence of
      both MMP-2 and MMP-9 in the majority of specimens, both cholesteatoma and deep
      meatal skin.

PMID- 9762498
TI  - Chest computerized tomography scanning in patients presenting with head and neck
      cancer.
AB  - Between 1 to 16% of patients with head and neck squamous cell carcinoma (HNSCC)
      have synchronous tumours; the majority (> 50%) occurring within the lung.
      Previous studies have relied upon endoscopy and chest radiographs. The aim of
      this study was to determine the incidence of synchronous intrapulmonary tumours
      in this group of patients using computerized tomography (CT) scanning. Over 36
      months, 111 consecutive patients were assessed at presentation by contrast
      enhanced CT scanning from the skull base to the diaphragm. Chest scans showed
      intrapulmonary lesions in 17 patients and 10 have, with time, been confirmed as
      neoplastic. These allowed treatment of three primary bronchial carcinomas
      following radical treatment of the index tumour and cancellation of radical
      treatment in five patients with metastases. Two patients with possible metastases
      at presentation underwent radical treatment to the index tumour with subsequent
      follow-up confirming metastatic chest disease. All 10 patients eventually died of
      either locoregional or metastatic disease. This is one of the first prospective
      reports of chest scanning in patients with head and neck cancer. An additional
      chest scan in this group, many of whom undergo a staging scan of the neck,
      requires an extra 10 min with no further contrast and in this study yielded a
      synchronous tumour rate of 9%.

PMID- 9762499
TI  - Vocim analysis of laryngeal images: is breathiness related to the glottic area?
AB  - The aim of this study was to determine the relationship between glottic space and
      breathy voice. Using a new computerized method of analysing the glottic area of
      video images with the Vocim computer system, 16 patients with a vocal cord palsy
      and 31 with non-organic dysphonia were examined. The quality of the breathy voice
      was assessed and correlated with the size of the glottic space during phonation.
      There was a positive (r = 0.70) correlation between glottic area and breathy
      voice in vocal cord palsy. There was no correlation (r = 0.002) in non-organic
      dysphonia. Therefore in this study population, for vocal cord palsy, glottic area
      is the dominant feature in determining voice quality. This relationship is not
      maintained in non-organic dysphonia.

PMID- 9762500
TI  - Laser Assisted Uvulopalatoplasty: an objective evaluation of the technique and
      results.
AB  - The operation of Laser Assisted Uvulopalatoplasty (LAUP) as described by Kamami
      is now becoming more commonly used in the treatment of snoring and obstructive
      sleep apnoea. The authors have treated 95 snoring patients, varying the lengths
      of the soft palate incisions and percentage of uvula excised. All operations were
      carried out under general anaesthesia using a CO2 laser. Pilot studies showed
      incisions that are 25% of the distance between the free edge of the soft palate
      to the hard palate junction and excision of 50% of the uvula give good results
      with minimal complications. A further study using these parameters was conducted
      and postoperative evaluation including polysomnography confirmed this procedure
      to be effective in reducing snoring levels both subjectively and objectively.

PMID- 9762501
TI  - Ototoxicity and topical eardrops.
AB  - Topical aminoglycoside ear drops are theoretically acknowledged to be potentially
      ototoxic when administered in the presence of a tympanic membrane perforation.
      Although the development of clinical ototoxicity appears to be rare, nine well
      documented and incontrovertible cases (12 ears in total) of iatrogenic topical
      vestibulotoxicity are presented, representing the largest series in the English
      language world literature to date. All patients were treated with the topical
      gentamicin-containing ear drops Garasone, (betamethasone sodium phosphate and
      gentamicin sulphate) for prolonged periods. Toxicity was found to be primarily
      vestibular rather than cochlear. Further review of five previously reported cases
      in addition to the findings from another four patients identified with topical
      ototoxicity are described. Although compensation occurred in unilateral cases the
      disability in bilateral cases was typically severe and often resulted in
      litigation.

PMID- 9762502
TI  - Histological analysis of the greater auricular nerve and its use as a graft.
AB  - Many factors are involved in successful nerve grafting. Morphometric similarity
      between donor and recipient nerve is one of these factors. A histological study
      was undertaken to determine the suitability of the greater auricular nerve as a
      graft in head and neck surgery. Nerves were obtained from fresh human cadavers
      and evaluated for length, total cross-sectional area, total fascicular cross
      sectional area and fascicular number, at three separate points along the nerve.
      Comparisons were made with similar studies of the sural and facial nerve. The
      study confirms the clinical view that the greater auricular nerve is ideal when
      short sections of graft are required in head and neck surgery.

PMID- 9762503
TI  - Power-frequency fields and cancer.
AB  - There is a widespread public perception that exposure to "EMF" is linked to
      cancer. This concern stems largely from a few epidemiological studies that appear
      to show an association between cancer and residence near power lines. However,
      the epidemiological evidence for such a link falls far short of that needed to
      conclude that a causal relationship exists, and examination of the biophysics
      leads to the conclusion that biological effects are implausible at the field
      strengths encountered in environmental settings. In a case such as this, where
      the epidemiological evidence for a link between an agent and a disease is weak to
      nonexistent and the effect is biophysically and/or biochemically implausible,
      laboratory evidence becomes critical for risk evaluation. The mechanisms of
      carcinogenesis are sufficiently well established that laboratory studies can be
      used to assess whether an agent has carcinogenic potential. There are
      approximately 100 published reports that have looked for evidence that power
      frequency fields have genotoxic or epigenetic activity. These studies have found
      no replicated evidence that power-frequency fields have the potential to either
      cause or contribute to cancer. Of the few studies that have shown some evidence
      for carcinogenic activity, most have used exposure conditions with little
      relevance to real world exposure, none have been replicated, and many have failed
      direct attempts at replication. In conjunction with the epidemiology and
      biophysics, this leads to the conclusion that a causal association between power
      frequency fields and cancer is not only unproven, but rather unlikely.

PMID- 9762504
TI  - Biomedical concerns in wireless communications.
AB  - The last decade witnessed rapid development of new communication technologies and
      their broad acceptance at large. Digital wireless telephones are the most popular
      example of these technologies. There are two aspects of these technologies that
      are related to human health and therefore biomedical engineering. First, antennas
      of some devices are in close proximity to the user's head, thus possibly
      producing locally excessive energy deposition. Second, radiofrequency (RF)
      signals emitted are amplitude modulated at extremely low frequencies, potentially
      eliciting different biological effects from those of unmodulated RF radiation.
      Recent progress in addressing these two issues is reviewed in this article.
      Another area of research and concern not covered here is electromagnetic
      interference (EMI) with medical devices. Considerable research has been conducted
      on the development of a new method for numerical and experimental evaluation of
      the spatial distribution of the power deposition in tissue. Improved implantable
      electric field probes and automated scanning systems are presently available.
      With respect to numerical evaluation of electric fields in tissue, the finite
      difference time domain (FDTD) technique has proven to be a useful and accurate
      tool. These developments also are critical in view of the regulatory requirements
      now imposed on mobile/portable transmitters. Similarly, significant research
      effort on biological effects of modulated fields has been undertaken. Most of the
      studies are still in progress, and further research agendas have been proposed.

PMID- 9762505
TI  - Evolution of the cohort study.

PMID- 9762506
TI  - Outcomes in cohort studies.

PMID- 9762507
TI  - Methodological issues for biomarkers and intermediate outcomes in cohort studies.

PMID- 9762508
TI  - Exposure measurement in cohort studies: the challenges of prospective data
      collection.
AB  - Cohort study designs have several advantages over case-control studies in terms
      of exposure measurement. If exposure measurement occurs before disease
      occurrence, cohort studies are much less prone to differential measurement error.
      Prospective data collection should also reduce measurement error due to poor
      recall of past exposures. The primary drawback of cohort studies is the large
      sample size leading to high data collection costs. Several approaches to reduce
      such costs have been discussed in this presentation, such as selection of lower
      cost measurement methods and fully measuring the exposure only on a subsample of
      the cohort (e.g., nested case-control design). However, other innovative
      approaches to reduce costs are needed. In addition, study reviewers should also
      consider that the higher costs are justified in relation to the several benefits
      of this study design, which include not only less measurement error, but also
      less susceptibility to selection bias and often the ability to study multiple
      disease outcomes. Improving the accuracy of exposure measurement is increasingly
      important for cohort studies as we move on to the study of exposures that are
      difficult to measure or to those with lower relative risks of disease. In such
      studies, attenuation of the relative risk by the effects of measurement error can
      lead to failure to detect an association between exposure and disease. The
      validity of exposure measurements could be improved by a better understanding of
      the biologically active agent and etiologically important time period of the
      exposure-disease relation, and by incorporating these into the measure. Long-term
      cohort studies which cover the etiologically relevant time period could improve
      the accuracy of measures of exposures by use of repeated biologic measures or
      repeated updates of self-reported exposures. Measurement error also can be
      reduced by judicious choice of a cohort to study and by careful attention to
      quality control procedures. Continued emphasis on the evaluation and improvement
      of the measurement properties of instruments used in epidemiologic studies will
      improve the validity of the results of cohort studies.

PMID- 9762509
TI  - Retaining and tracking cohort study members.
AB  - The only way to ensure that losses to follow-up have not biased study results is
      to keep all losses to an absolute minimum. Since more complete follow-up leads to
      the identification of additional disease events, the effort spent in locating
      cohort members also improves the precision as well as the validity of the study
      results. This presentation reviewed approaches for maximizing retention and
      minimizing loss to follow-up, including the importance of communicating the
      expectations of participation and collecting personal information at baseline,
      conducting frequent personal and mail contact, and providing incentives for
      participation. Response rates can be increased by repeated attempts to contact
      each cohort member using a range of approaches (e.g., telephone, mail, personal
      contacts) and by other procedures specific to mailed questionnaires, telephone
      interviews, or in-person visits. Lost participants can be traced by use of the
      NCOA system and contact with other local, state, and national sources. Finally,
      for those participants who are unable or unwilling to continue or who cannot be
      found, proxy interviews and/or use of the National Death Index may provide
      information on the outcomes of interest and vital status. Additional research
      evaluating the efficacy of the various approaches to retention and tracking is
      needed to help investigators learn how to best apply study resources to retain
      and keep track of the largest possible number of cohort members.

PMID- 9762510
TI  - Quality assurance and quality control in longitudinal studies.
AB  - As we have presented, it is evident that cohort studies are confronted with their
      own special, non-trivial issues of quality assurance and quality control. Such
      studies are typically large-scale designs and involve an extensive amount of data
      to be collected and processed, the quality of which depends on a variety of
      factors related to study personnel and equipment. The fact that data are
      collected over an extended period of time and at several centers greatly
      increases the magnitude of the data processing task, significantly increasing the
      likelihood of discrepancies and measurement error in the data. As presented in
      tables 1 and 2, the quality assurance and quality control procedures span the
      entire course of the study and include a multitude of tasks. Such tasks are
      delegated to various committees and/or are undertaken by participating centers,
      all of which must take responsibility for understanding, implementing, and
      following through on all procedures that maximize data quality. The quality of
      the quality assurance/quality control process is highly correlated with the
      quality of the communication within and between centers and all researchers.
      Maintaining standardization of procedures across centers and long-term stability
      of equipment and analytic procedures are integral components of quality control.
      In conclusion, the magnitude of the quality control process in a multicenter
      longitudinal study should not be underestimated, requiring a significant
      commitment of study resources. The quality control process is key to the
      integrity of the study, and an integral part of the design of the study. In a
      well-designed study, with a good quality control process and dedication to the
      process by the research team, the validity of the conclusions of the cohort study
      can be established.

PMID- 9762511
TI  - Population-based cohort studies.

PMID- 9762512
TI  - Approaches for conducting large cohort studies.

PMID- 9762513
TI  - Developments in occupational cohort studies.

PMID- 9762514
TI  - Use of computerized record linkage in cohort studies.

PMID- 9762515
TI  - New techniques for the analysis of cohort studies.

PMID- 9762516
TI  - Perspective: cohort studies.

PMID- 9762517
TI  - The biological significance of plasmalogens in defense against oxidative damage.
AB  - The phospholipid class of plasmalogens is ubiquitously found in considerable
      amounts as a constituent of mammalian cell membranes and of plasma lipoproteins.
      Plasmalogens are more susceptible to oxidative reactions compared to their fatty
      acid ester analogues, due to the reactivity of their enolether function. Studies
      on plasmalogen-deficient cell lines lead to the proposal that these ether lipids
      serve as endogenous antioxidants. No clear conclusions regarding the
      antioxidative effects of plasmalogens could be drawn from studies in patients of
      different ages with peroxisomal deficiency disorders. A defective peroxisomal
      plasmalogen synthesis is not necessarily associated with other defects in the
      metabolism of peroxisomes, as has been established in a cell line recently. In
      different mammalian tissues a decrease of plasmalogens with age was described.
      Moreover, an accumulation of plasmalogen oxidation products was measured in brain
      of old cattle compared to young ones. In pathologic conditions associated with
      oxidative stress like in spinal cord ischemia and reperfusion, plasmalogen levels
      varied inversely according to the oxidative burden. Oxidation products of
      plasmalogens increased with time of ischemia in infarcted porcine heart tissue.
      Enrichment of lipoproteins with plasmalogens increased their oxidative
      resistance, which was diminished in the case of LDL particles in patients with
      coronary arteriosclerosis. In red cell membranes plasmalogens were reduced with
      donor age and in hyperlipidemia. Under lipid lowering therapy with lovastatin an
      increase was observed, indicating a possible antioxidative impact of this
      treatment. Taken together, there is good evidence that plasmalogens are effective
      as endogenous antioxidants. However, more experimental approaches not confounded
      by other lipolytic processes are needed to establish this role of plasmalogens.

PMID- 9762518
TI  - The importance of inflammatory mechanisms in Alzheimer disease.
AB  - Lesions in such chronic neurodegenerative disorders as Alzheimer disease (AD),
      Parkinson disease, the parkinsonism dementia complex of Guam, and amyotrophic
      lateral sclerosis have associated with them a variety of proteins known to be
      involved in inflammatory processes. This is particularly true of AD, where
      inflammatory reactions are thought to be important contributors to the neuronal
      loss. Proteins present include complement proteins, complement inhibitors, acute
      phase reactants, inflammatory cytokines, proteases, and protease inhibitors.
      Studies of cultured human astrocytes and microglia, obtained from postmortem
      brain, have established that nearly all of these proteins are produced by one or
      another of these cell types. Human neurons also produce many inflammatory
      proteins and their inhibitors, creating complex interactions. Accumulations of
      amyloid and extracellular tangles apparently act as irritants, causing the
      activation of complement, the initiation of reactive changes in microglia, and
      the release of potentially neurotoxic products. Such products include the
      membrane attack complex, oxygen free radicals, and excess glutamate. Twenty
      epidemiological studies that have been published to date indicate that
      populations taking antiinflammatory drugs have a significantly reduced prevalence
      of AD or a slower mental decline. One small clinical trial with indomethacin
      showed arrest of the disease over a six-month period. Therapeutic intervention in
      key inflammatory processes holds great promise for the amelioration of AD and
      possibly other neurodegenerative disorders.

PMID- 9762519
TI  - Human urothelial carcinomas--a typical disease of the aged: the clinical utility
      of human chorionic gonadotrophin in patient management and future therapy.

PMID- 9762520
TI  - The two-process model of cellular aging.
AB  - To understand the mechanism of aging at the cellular level, cellular senescence
      has been extensively studied as an experimental model of aging in vitro. Although
      several hypotheses have been proposed for the mechanism of cellular senescence,
      none of them could give a comprehensive framework to the mechanism. In this
      study, we showed our results of extensive computer simulation designed to
      identify possible molecular models of cellular senescence. By examining
      representative cases of various molecular models, we elucidated the requirements
      for the plausible mechanism of cellular senescence. Based on these simulation
      results, we proposed a new molecular model of cellular senescence--the two
      process model. In this model, we assumed that two independent, but time-aligned
      regulatory processes functioned in individual cells. We defined these two
      processes as S- and C-processes. The S-process mainly determines the rate of
      decline in the proliferative potential of the cell population. The simulation
      results suggested that the growth-inhibitory cell-to-cell interaction was
      required to drive the S-process. The C-process determines the latent
      proliferative potential of individual cells. The effector genes for the C-process
      are suggested to be regulated by a certain threshold-type mechanism. Both growth
      kinetics and senescence-associated gene expression were generated with high
      accuracy by the combined effect of these two processes. We also succeeded in
      simulating the effects of simian virus 40 large T antigen and its inducible
      variant on cellular senescence. From these theoretical considerations, we discuss
      the validity of the two-process model and the possible involvement of the
      heterochromatin structure as a determinant of the replicative lifespan of cells.

PMID- 9762521
TI  - A strategy for identifying biomarkers of aging: further evaluation of hematology
      and blood chemistry data from a calorie restriction study in rhesus monkeys.
AB  - We examined a dataset derived from a battery of hematology and blood chemistry
      tests to identify candidate biomarkers of aging in a sample of 33 male rhesus
      monkeys (Macaca mulatta) ranging in age from 4-27 years. About half this sample
      comprised an experimental group subjected to 30% calorie restriction for six to
      seven years compared to the control group fed the same nutritionally fortified
      diet to approximate ad lib levels. Variables that met the following criteria were
      selected: (1) longitudinal change within the cohorts of control monkeys; (2)
      cross-sectional correlation with age across the adult lifespan in the control
      group; (3) stability of individual differences within all groups; and (4) no
      obvious redundancy with other selected variables. Five variables emerged from
      this step-wise selection, including the percentage lymphocytes, and serum levels
      of alkaline phosphatase, albumin, creatinine, and calcium. These variables were
      then submitted to a principal component analysis, which yielded a single
      component accounting for about 58% of the total variance. Based on this marked
      degree of covariance, these candidate biomarkers of aging could be combined into
      a biological age score (BAS) for the control and experimental groups. When
      chronological age was regressed onto BAS, the slopes of the control and
      experimental groups could be compared. Although a trend toward a slower aging
      rate in calorie-restricted monkeys was apparent, this analysis did not detect a
      statistically significant difference in the rate of aging between these groups
      estimated by this index. Despite this result, a logical strategy was confirmed
      for expanding the search for candidate biomarkers of aging to apply to this and
      to other studies assessing interventions that purport to affect the rate of aging
      in long-lived species.

PMID- 9762522
TI  - Effect of high-glucose concentrations on the expression of collagens and
      fibronectin by fibroblasts in culture.
AB  - Extracellular matrix macromolecules such as collagen and fibronectin are
      progressively altered during aging and age-related diseases like diabetes. We
      investigated the effect of high-glucose concentration (mimicking diabetic
      conditions) and the influence of in vitro cell aging [comparing 4th-passage
      fibroblasts (P4) to 15th-passage fibroblasts (P15)] on collagen and fibronectin
      synthesis. Fibroblasts were incubated at postconfluency with radiolabeled
      precursors, [3H] proline for collagen, [35S] methionine for fibronectin. We
      report that in control conditions (5 mM glucose) collagen III production
      increased with in vitro cell aging. High glucose concentrations (10 and 15 mM)
      increased specifically collagen III synthesis both at the mRNA and protein
      levels, without alteration of collagen I production in P4 and P15 cells.
      Fibronectin synthesis was also increased both during in vitro cell aging and in
      high glucose-treated P4 fibroblasts. Taken together, these data suggest
      similarities between changes of phenotypic expression of collagen and fibronectin
      induced by in vitro cell aging and conditions imitating diabetes.

PMID- 9762523
TI  - Identification of altered expression of ADP/ATP translocase during cellular
      senescence in vitro.
AB  - In this study, we have used the mRNA differential display technique to
      investigate the changes in gene expression that occur in the process of cellular
      aging. A number of cDNAs whose corresponding mRNAs are either increasingly or
      decreasingly expressed in senescent cells were thereby isolated. Through DNA
      sequencing, one of these differentially displayed mRNAs was identified as
      mitochondrial ADP/ATP translocase. The altered expression of ADP/ATP translocase
      in different stages of senescent fibroblasts was further confirmed by Northern
      blots and semiquantitative RT-PCR. Our results demonstrate that expression of
      ADP/ATP translocase is progressively decreased during the process of in vitro
      cellular senescence. Further analyses with MTT assays indicate that the decreased
      expression of ADP/ATP translocase in senescent cells is in parallel with the
      decline of mitochondrial functions, suggesting that altered expression of this
      important mitochondrial enzyme might play an active role in the process of
      cellular senescence.

PMID- 9762524
TI  - The effect of exercise training in cold on shivering and nonshivering
      thermogenesis in adult and aged C57BL/6J mice.
AB  - To understand the mechanisms of improvement of cold-induced heat production in
      aged mice following exercise training, the relative contributions of shivering
      and nonshivering thermogenesis to cold-induced metabolic responses were assessed
      in adult and aged C57BL/6J male mice, which inhabited sedentarily at room
      temperature, or were subjected either to a regimen of moderate intensity exercise
      training at 6 degrees C, or to sedentary repeated exposures to the same
      temperature. The main findings were that (1) aged mice had greater cold-induced
      nonshivering thermogenesis, but lower shivering than adult mice; (2) exercise
      training in a cold environment enhanced cold-induced nonshivering thermogenesis
      in adult mice, but suppressed it in aged animals; (3) exercise training in a cold
      environment increased shivering thermogenesis in both age groups, but this
      increase was much greater in aged mice; (4) the increase of cold-induced
      shivering thermogenesis was mainly responsible for increased cold tolerance in
      aged mice after exercise training in a cold environment.

PMID- 9762525
TI  - Age-associated differences in neutrophil oxidative burst (chemiluminescence).
AB  - Phagocytic defensive functions consist of a sequence of events, including
      migration, phagocytosis, secretion, and the release of reactive oxygen species
      (ROS). The last of these (also called "oxidative burst") has not received due
      attention in the elderly, even though it can be considered the most important
      event in the process of killing an invading microorganism. The aim of the present
      study was to investigate the oxidative burst activity of polymorphonuclear
      neutrophil leukocytes (PMNs) in relation to age, using a technique that
      specifically identifies ROS production: luminol-amplified chemiluminescence
      (LACL). Besides the use of LACL, a particular feature of the study was the use of
      five rather than just one or two different stimulants: two particulate (Candida
      albicans and zymosan) and three soluble ones [N-formyl-methionyl-leucyl
      phenylalanine (fMLP), phorbol 12 myristate 13 acetate (PMA), and
      polyanetholesulfonate (liquoid)]. This approach allowed us to observe a dichotomy
      between the effects of Candida and zymosan (particulates), which were not
      significantly different in the elderly subjects compared to the young controls,
      and those of fMLP, PMA, and liquoid (solubles), which showed a significant
      reduction in LACL in the elderly group. Considering the different results
      obtained with the various stimulants adopted that are all believed to have NADPH
      oxidase as a common final target of oxidative burst, it may be postulated that
      aging can influence the different transductional pathways in different ways.

PMID- 9762526
TI  - Environmental influence on age-related changes of human lymphocyte membrane
      viscosity using severe combined immunodeficiency mice as an in vivo model.
AB  - Peripheral blood lymphocytes (PBL) of healthy elderly people show increased
      plasma membrane viscosity compared to young subjects, that inversely correlates
      with lymphocyte proliferation after mitogen stimulation in vitro. Maintenance of
      a constant membrane viscosity, which is necessary for proper cell function, is
      crucially dependent on the membrane lipid composition. The cellular lipid
      metabolism, and thus lymphocyte function, may be subject to modulation by diet or
      drugs. To study the susceptibility of membrane viscosity to environmental
      conditions, we established an in vivo model using severe combined
      immunodeficiency (SCID) mice: human peripheral blood lymphocytes from healthy
      young and old subjects were engrafted for three days intraperitoneally into SCID
      mice to offer identical environmental conditions. First, we demonstrate that
      human lymphocytes can take up and utilize murine lipoproteins: engrafted human
      PBL can participate in the mouse lipid metabolism, and an exchange of membrane
      lipids in vivo is, therefore, possible. Second, plasma membrane viscosity was
      determined before and after engraftment: before engraftment, PBL from the elderly
      showed a significantly higher membrane viscosity than that from young controls,
      but this difference vanished during engraftment into SCID mice, wherein cells
      from both age groups exhibited nearly identical values. It was, therefore,
      concluded that lymphocyte membrane viscosity is influenced by environmental
      factors, and that the age-related increase is, in principle, reversible.

PMID- 9762527
TI  - Effect of dehydroepiandrosterone (DHEA) on intestinal mucosal immunity in young
      adult and aging rats.
AB  - The present study assesses the effectiveness of oral DHEA on the intestinal
      mucosal immune response in aging rats. Young adult (6 months) and aging (21
      months) female rats received powdered rat chow with or without 0.2% DHEA for 23
      days. The animals were immunized intraduodenally with either cholera toxin (CTx)
      or vehicle alone and boosted two weeks later. Seven days after boosting, serum,
      bile, small intestinal tissue, and liver were collected for analysis. Anti-CTx
      IgA antibody titers were measured in serum and bile and the concentration of anti
      CTx antibody containing cells (ACCs) in the small intestinal lamina propria and
      liver were determined by quantitative immunohistochemistry. Intergroup
      comparisons indicated that there was only one significant difference in serum and
      none in bile anti-CTx IgA titers between CTx-immunized animals fed DHEA or the
      diet alone. Immunohistochemical analysis determined that the density and
      distribution patterns of ACCs within the lamina propria were unaffected by DHEA.
      Both DHEA-treated and control young immunized animals exhibited similar numbers
      of ACCs. Only 40% of the aging rats responded to intraduodenal immunization with
      CTx, as determined by the presence of ACCs in the intestine, regardless of the
      presence or absence of DHEA in the diet. These data suggest that DHEA in the diet
      does not enhance the intestinal mucosal immune response to intraduodenal CTx in
      either young adult or aging rats.

PMID- 9762528
TI  - Norepinephrine kinetics in older women: relationship to physical activity and
      blood pressure.
AB  - The sympathetic nervous system participates in the regulation of carbohydrate,
      lipid, and energy metabolism, and has been implicated in the pathogenesis of
      hypertension and obesity. Increased sympathetic nervous system activity with age
      may alter disease risk and contribute to the development of certain chronic
      diseases. Thus, we examined possible determinants of sympathetic nervous system
      activity in older normotensive women from infusions of tritiated norepinephrine
      (NE) to estimate rates of norepinephrine appearance and clearance. A secondary
      aim was to examine the association between norepinephrine kinetics and mean
      supine arterial blood pressure. Twenty-two older women (65.7 +/- 5.7 years) were
      characterized for resting NE kinetics, body composition, body fat distribution,
      peak aerobic capacity, leisure time physical activity energy expenditure (LTA),
      dietary carbohydrates, and daily energy intake. Analysis of univariate
      correlations revealed that only the LTA was significantly correlated with plasma
      NE appearance (r = 0.54, p < 0.01). Stepwise regression analysis identified LTA
      as the only significant predictor of plasma NE appearance rate with a total R2 =
      0.29. The waist-to-hip ratio was selected as the only significant predictor of
      mean arterial blood pressure with an R2 = 0.30. When forced into the model,
      plasma NE appearance explained only 1% of the unique variance in mean arterial
      blood pressure. In summary, we found that: (1) higher levels of physical activity
      are related to higher plasma NE appearance in older women; (2) greater central
      body fatness is an independent predictor of mean arterial blood pressure; and (3)
      plasma NE appearance rate is a minor contributor to variation in mean arterial
      blood pressure in older, normotensive women.

PMID- 9762529
TI  - Health care and the market.

PMID- 9762530
TI  - Caring for "difficult" patients.

PMID- 9762531
TI  - Caring for "difficult" patients.

PMID- 9762532
TI  - Remodelling IRBs.

PMID- 9762533
TI  - Deaf culture, cochlear implants, and elective disability.
AB  - The use of cochlear implants, especially for prelingually deafened children, has
      aroused heated debate. Members and proponents of Deaf culture vigorously oppose
      implants both as a seriously invasive treatment of dubious efficacy and as a
      threat to Deaf culture. Some find these arguments persuasive; others do not. And
      in this context arise questions about the extent to which individuals with
      disabilities may decline treatments to ameliorate disabling conditions. When they
      do so, to what extent may they call upon society to provide supportive services
      and accommodations?

PMID- 9762534
TI  - Multiplex genetic testing. The Council on Ethical and Judicial Affairs, American
      Medical Association.
AB  - As panels of multiple genetic tests become increasingly available, clinicians
      face new challenges in helping patients understand the nature of these tests.
      Diagnostic tests for conditions that inevitably lead to disease, "susceptibility"
      tests that reveal heightened risk of disease, and tests for carrier status raise
      different concerns about informed consent and pose different needs for
      counseling. Clinicians must understand the implications of different kinds of
      tests, and of different arrays of tests in multiple panels, if multiplex tests
      are to be used wisely in clinical practice.

PMID- 9762535
TI  - Meaning what you sign.

PMID- 9762536
TI  - Should psychiatrists serve as gatekeepers for physician-assisted suicide?

PMID- 9762537
TI  - What could have saved John Worthy?

PMID- 9762538
TI  - Autonomy and assisted suicide. The execution of freedom.
AB  - Proponents of assisted suicide who base their arguments on autonomy err in ways
      that are little attended to. In the absence of a substantive theory of the good,
      in neither a descriptive nor an ascriptive sense can the concept of autonomy
      distinguish those acts that should be morally prohibited from those that may be
      permitted. And to impose a particular theory of the good, whether individual
      liberty or the sanctity of life, violates the autonomy of those who do not share
      a commitment to that theory.

PMID- 9762539
TI  - Adam and the implant.

PMID- 9762540
TI  - Cash up front.

PMID- 9762541
TI  - Grading and scoring in histopathology.
AB  - In many areas of histopathology a nominal category, such as a diagnosis of breast
      carcinoma, does not give enough information for the referring clinician to make
      decisions about patient prognosis and treatment. Therefore scoring and grading
      systems have been developed which provide additional information. This article
      reviews the principles behind these systems with particular reference to the
      relationships between the natural clustering (or nonclustering) of cases and the
      imposition of arbitrary class boundaries on such distributions. The difference
      between real numbers and the ordinal categorical numeric labels, which are often
      produced by histopathology scoring systems, is discussed. The reproducibility of
      scoring and grading systems is reviewed and generic suggestions are given for
      developing new systems and for their validation.

PMID- 9762542
TI  - Gains and losses of CD44 expression during breast carcinogenesis and tumour
      progression.
AB  - AIMS: This study was performed to investigate whether the CD44 immunophenotype of
      breast lesions correlates with the clinical evolution and prognosis of breast
      cancer. METHODS AND RESULTS: One-hundred and fifty-two routinely processed
      normal, benign and malignant breast tissue samples were investigated by the
      following monoclonal antibodies: CD44s (F10-44-2), CD44v3 (3G5), CD44v4 (11.10),
      CD44v5 (VFF-8), CD44v6 (VFF-18), CD44v7 (VFF-9), CD44v9 (11-24) after wet
      autoclave pretreatment for antigen retrieval. We found that: (1) in normal breast
      tissues luminal epithelial cells lacked detectable CD44 in contrast to basal
      cells, which constitutionally expressed CD44s, v3, v5 v6 and v9 isoforms; (2) in
      the intraductal compartment of benign hyperplastic lesions, there was scattered
      or focal staining for CD44s, v5, v6, v7 and v9 isoforms; (3) in neoplastic
      lesions restricted neo-expression of CD44v3 and v4 was detected; and (4) the CD44
      immunophenotype of invasive breast carcinomas was influenced largely by
      differentiation grade, steroid receptor status of the tumours and significantly
      correlated with metastatic involvement of the axillary lymph nodes. CONCLUSIONS:
      Qualitative and quantitative changes of CD44 expression are implicated in early
      stages of breast carcinogenesis. The restricted neo-expression of certain CD44
      isoforms in breast neoplasias suggests that CD44 might be a potential target for
      future antibody-based tumour therapy.

PMID- 9762543
TI  - Apoptosis in nasopharyngeal carcinoma as related to histopathological
      characteristics and clinical stage.
AB  - AIMS: We investigated the significance of apoptosis, using the terminal
      deoxynucleotidyl transferase mediated dUTP-digoxigenin nick end-labelling method,
      in nasopharyngeal carcinoma biopsy samples. METHODS AND RESULTS: The apoptotic
      index (AI) in 50 nasopharyngeal carcinomas was compared with various
      histopathological features and clinical stage. Also, the AI was correlated with
      p53, bcl-2 and Ki67 expression by immunohistochemistry. In histopathological
      studies, the AI was significantly higher in mixed cellular type (MC) than in
      keratizing squamous cell type (KS) and spindle cell type (SC) (P < 0.001) which
      worsens prognosis. In tumour stage analyses, AI was higher in early stage (stage
      2 and 3) than in high stage (stage 4). In addition, there was a significant
      correlation between the AI and p53 expression (P < 0.001) but not with
      proliferative activity (P = 0.15). In NPC containing p53 protein positive tumour
      cells, there was a significantly higher apoptotic rate. CONCLUSIONS: These
      findings indicate that apoptosis is related to type and stage of nasopharyngeal
      carcinoma. They also confirm the role of p53 in regulating tumour apoptosis.

PMID- 9762544
TI  - Apoptosis and expression of bcl-2 protein are inverse factors influencing tumour
      cell turnover in primary carcinoid tumours of the lung.
AB  - AIMS: This study evaluates potential regulating factors in primary pulmonary
      carcinoid tumours, 16 typical and four atypical samples, with special emphasis on
      apoptosis and the bcl-2 gene family. Furthermore, p53-related oncogenes were
      analysed in a search for associated biological parameters. METHODS AND RESULTS:
      The in-situ end-labelling technique (ISEL) was used to determine apoptotic cells,
      in addition to immunohistochemical methods, which were used to investigate the
      expression of the Ki67 antigen (avidinbiotin complex (ABC) method) and bcl-2, bcl
      x, p53, p21/waf1, p27 and mdm-2 proteins (catalysed reporter deposition (CARD)
      technique). The incidence of apoptotic tumour cells was significantly enhanced in
      typical carcinoids. The bcl-2 protein was expressed to a higher degree in
      atypical carcinoids, which displayed a higher proliferative capacity as well. In
      contrast, bcl-x was observed predominantly in so-called typical carcinoids. The
      tumour cell turnover index was the most distinguishing parameter between both
      entities. All carcinoid tumours failed to show a staining for p53, p21/waf. p27
      and mdm-2 proteins. CONCLUSIONS: The different biological behaviour of the
      carcinoid tumours under study seems to be influenced by the bcl-2 gene family
      preventing programmed cell death. We speculate that this results in a more
      aggressive course in atypical carcinoid tumours.

PMID- 9762546
TI  - Skeletal muscle regeneration mimicking rhabdomyosarcoma: a potential diagnostic
      pitfall.
AB  - AIMS: We report three cases of skeletal muscle regeneration, of which two
      mimicked a small round cell tumour, especially a rhabdomyosarcoma. METHODS AND
      RESULTS: One case presented as an intramuscular mass, located in the right
      quadriceps of a 12-year-old male; the second patient was a 25-year-old football
      player who complained of painful left peroneus muscles; the third patient was a
      22-year-old male who underwent an amputation of the right thigh 5 days after
      right leg amputation due to limb crush. Histologically, muscle biopsy specimens
      showed a proliferation of small round cells, either infiltrating the striated
      muscle in a diffuse manner or growing within and around necrotic myofibres.
      Immunohistochemically and ultrastructurally, the cellular population was composed
      of two types of cells: phagocytic cells the nuclei of which occasionally showed a
      wreathlike arrangement around necrotic myofibres resulting in structures
      resembling Langhans-type multinucleated giant cells, and proliferating satellite
      cells showing enlarged nuclei, prominent nucleoli, mitotic figures, myogenic
      differentiation and fusion features in order to form regenerating myotubes.
      CONCLUSIONS: Muscle regeneration is a benign process that may occasionally mimic
      a small round cell proliferation resembling a lymphoma or an alveolar
      rhabdomyosarcoma with which it should not be confused.

PMID- 9762545
TI  - Differentiation of desquamative interstitial pneumonia (DIP) from pulmonary
      adenocarcinoma by immunocytochemistry.
AB  - AIM: After a misdiagnosis of pulmonary adenocarcinoma as desquamative
      interstitial pneumonia (DIP), we investigated whether immunohistochemical markers
      could differentiate these conditions. METHODS AND RESULTS: Three cases of DIP and
      one pulmonary adenocarcinoma masquerading as DIP were studied by light and
      electron microscopy. All cases were mucin-negative. The cases of DIP were CD68
      positive but cytokeratin-negative. The adenocarcinoma was cytokeratin-positive
      (AE1/3 and CAM5.2), as well as showing some CD68-positive cells. Markers for
      carcinoma (CEA, Ber-EP4, and Leu M1) were negative in all cases.
      Ultrastructurally the adenocarcinoma appeared to be derived from Type II
      pneumocytes. CONCLUSION: Before a diagnosis of DIP is made, cytokeratin markers
      should be used.

PMID- 9762548
TI  - Metallothionein expression in carcinoma of the gallbladder.
AB  - AIMS: Metallothioneins (MT) are sulphur-rich, low molecular-weight, intracellular
      metal-binding proteins with a possible role in carcinogenesis of some human
      tumours. Metallothionein expression in gallbladder cancer has not been studied
      previously. METHODS AND RESULTS: Immunohistochemical expression of
      metallothionein was studied in 42 gallbladders (27 cases of carcinoma of the
      gallbladder, eight chronic cholecystitis and seven cases of normal gallbladder).
      Metallothionein expression was significantly higher in cases with carcinoma of
      the gallbladder (70.37%) as compared to chronic cholecystitis (25%) and normal
      gallbladders (0%). There was a trend suggestive of increasing MT expression with
      increasing histological dedifferentiation of carcinoma of the gallbladder.
      CONCLUSIONS: The increased expression of MT in cases of carcinoma of the
      gallbladder may represent an increased exposure to heavy metals, which are known
      carcinogens, and may have a role in gallbladder carcinogenesis. Metallothionein
      over-expression in carcinoma of the gallbladder may be relevant to the poor
      prognosis and chemoresistance seen in these cases.

PMID- 9762547
TI  - Relationship between interleukin-6 and proliferation and differentiation in
      cholangiocarcinoma.
AB  - AIMS: Interleukin-6 (IL-6) has been implicated as a mediator of growth control in
      several human neoplasms. The significance of IL-6 expression in human
      cholangiocarcinoma was examined in this study. METHODS AND RESULTS: IL-6
      expression was examined in 43 surgically resected cholangiocarcinomas and a
      cholangiocarcinoma cell line CCKS1, derived from abdominal metastasis of
      moderately differentiated adenocarcinoma, by immunohistochemical and in-situ
      hybridization techniques. In non-neoplastic bile ducts, IL-6 was constitutively
      but weakly expressed. In surgical cases of cholangiocarcinoma, IL-6 was
      frequently and strongly expressed in the cytoplasm of well-differentiated
      cholangiocarcinoma, while its expression was decreased, and less intense or
      absent in moderately and poorly differentiated areas, respectively. IL-6 mRNA was
      detected in the cytoplasm of carcinoma cells of two cases of cholangiocarcinomas
      positive for IL-6. IL-6 was detected in hepatic bile from two cholangiocarcinoma
      cases studied. The proliferation antigen Ki67 was found to be more frequently
      expressed in IL-6 negative carcinoma cells than in IL-6 positive carcinoma cells
      (P < 0.01). In cultured carcinoma cells line CCKS1, IL-6, IL-6 mRNA and IL-6
      receptor alpha chain were detected in the cytoplasm of carcinoma cells,
      suggesting an autocrine effect of IL-6 on carcinoma cells. CONCLUSION: IL-6
      expression is inversely related to cell proliferation and positively related to
      differentiation in cholangiocarcinoma.

PMID- 9762549
TI  - Histological demarcation of lateral borders: an unsupportable criterion for
      distinguishing malignant melanoma from Spitz naevus and compound naevus.
AB  - AIMS: The objective of this study was to determine the validity of sharpness of
      lateral margins (an important component of the pattern analysis method) as a
      criterion for the histological distinction of naevi from malignant melanoma.
      METHODS AND RESULTS: The sharpness of lateral borders in a series of
      histologically unequivocal malignant melanomas, Spitz naevi and compound naevi,
      chosen at random from dermatopathology slide archives, was determined. The
      incidence of poor demarcation of lateral borders in malignant melanomas was about
      equal to that of Spitz naevi and was significantly less than in compound naevi.
      The sharpness of lateral borders frequently varies with level of sectioning.
      CONCLUSIONS: The proposal that malignant melanomas have a significantly greater
      incidence of poor demarcation of lateral borders than benign melanocytic
      neoplasms (Spitz naevi and compound naevi) was shown to be without validity on
      cited empirical grounds as well as theoretical grounds (the lack of constancy of
      pattern from a 3-dimensional standpoint).

PMID- 9762550
TI  - Familial mediterranean fever and acute myocardial infarction secondary to
      coronary vasculitis.
AB  - AIMS: We report a case study to elucidate the pathogenesis of polyarteritis
      nodosa (PAN) type vasculitis, a rare complication of familial mediterranean fever
      (FMF). METHODS AND RESULTS: A woman with amyloidosis complicating FMF underwent a
      cadaveric renal transplantation and 5 years later suffered an acute myocardial
      infarction secondary to an isolated coronary vasculitis. CONCLUSIONS: The
      histopathological findings of the vasculitis were not in keeping with PAN. We
      postulated that the pathogenesis of vasculitis in FMF is different from that of
      the classic PAN and might be similar to the mechanism of the serosal
      inflammation.

PMID- 9762551
TI  - Appendiceal inflammation in ulcerative colitis.
AB  - AIMS: Previous uncontrolled reports have suggested that appendiceal inflammation
      may occur as a discontinuous lesion in ulcerative colitis. This study aims
      semiquantitatively to compare the prevalence and histological features of
      appendiceal inflammation in patients with ulcerative colitis and Crohn's disease,
      using colonic carcinoma and acute appendicitis specimens as controls. METHODS AND
      RESULTS: Surgical pathology records and original histological slides for the
      period 1980-1994 were examined. The prevalence of appendiceal inflammation in
      ulcerative colitis (24/50, 48%), was higher than in colonic carcinoma (5/65, 8%,
      P < 0.001), but was similar to that in Crohn's disease (14/27, 52%). Appendiceal
      inflammation with caecal sparing was seen in nine out of 24 specimens with
      ulcerative colitis (37%), two out of nine (22%) with Crohn's disease and five out
      of 65 (8%) with colonic carcinoma. Inflamed appendixes from patients with
      inflammatory bowel disease showed histological features typical of ulcerative
      colitis and Crohn's disease rather than acute appendicitis and were significantly
      less likely to have transmural inflammation. There had been a previous
      appendicectomy in 3% of ulcerative colitis patients compared with 8% of colonic
      carcinoma specimens and 21% (P < 0.01) Crohn's disease controls. CONCLUSION: In
      ulcerative colitis, as in Crohn's disease, appendiceal inflammation commonly
      occurs as a skip lesion and histologically resembles the colonic disease rather
      than acute appendicitis. The low prevalence of appendicectomy supports the
      hypothesis that the appendix itself may have a central role in the pathogenesis
      of ulcerative colitis.

PMID- 9762552
TI  - Applications of the microbiopsy technique in non-cervical cytology: where
      cytology and histology meet.
AB  - AIM: To evaluate a recently developed technique allowing the removal and
      processing for histology of thick tissue fragments, called microbiopsies, from
      noncervical cytology specimens. METHODS AND RESULTS: Forty-five non-cervical
      smears from malignant tumours which contained microbiopsies were selected and
      processed. Sufficient sections could be cut in most cases for haematoxylin and
      eosin and an extensive panel of immunostaining. Seventy-one per cent of
      histological slides from the microbiopsies were representative of the tumour and
      confirmed the diagnosis. In 29% of the cases they were too small, contained non
      representative tissue or showed extensive necrosis. Surprisingly, immunostaining
      results were at least the same and often better than those observed in routine
      formalin-fixed, paraffin-embedded tissue. Immunostaining profiles allowed
      distinction of tumour subtypes. Antigen retrieval techniques could be avoided in
      all cases. CONCLUSIONS: Application of the microbiopsy technique in routine
      cytology smears containing microbiopsies is helpful, particularly in those cases
      in which the diagnosis is not clear on the basis of the cytology smear and in
      cases in which there are not enough cytology slides for immunohistochemical
      examination.

PMID- 9762553
TI  - Pigmented squamous cell carcinoma of nasal cavity.

PMID- 9762554
TI  - Primary extraskeletal osteosarcoma of the penis with a malignant fibrous
      histiocytoma-like component.

PMID- 9762555
TI  - Hepatoid adenocarcinoma of the stomach with extensive neuroendocrine
      differentiation and a coexisting carcinoid tumour.

PMID- 9762556
TI  - Inverted papilloma-like transitional cell carcinoma of the uterine cervix.

PMID- 9762557
TI  - Malignant fibrous histiocytoma in a child's hand.

PMID- 9762558
TI  - Paratesticular composite tumour of epididymal-like and mucinous cells of low
      malignant potential.

PMID- 9762559
TI  - Intestinal nematode parasites, cytokines and effector mechanisms.
AB  - Laboratory models of intestinal nematode infection have played an important role
      in developing our understanding of the immune mechanisms that operate against
      infectious agents. The type of helper T cell response that develops following
      infection with intestinal nematode parasites is critical to the outcome of
      infection. The early events that mediate polarisation of the helper T cell
      subsets towards either Th1 or Th2 during intestinal nematode infection are not
      well characterised, but it is likely that multiple factors influence the
      induction of a Th1 or Th2 type response, just as multiple effector mechanisms are
      involved in worm expulsion. Costimulatory molecules have been shown to be
      important in driving T helper cell development down a specific pathway as has the
      immediate cytokine environment during T cell activation. If helper T cells of the
      Th2 type gain ascendancy then a protective immune response ensues, mediated by
      Th2 type cytokines and the effector mechanisms they control. In contrast, if an
      inappropriate Th1 type response predominates the ability to expel infection is
      compromised. Equally important is the observation that multiple potential
      effector mechanisms are stimulated by nematode infection, with a unique
      combination operating against the parasite depending on nematode species and its
      life cycle stage. Despite the close association between intestinal nematode
      infection and the generation of eosinophilia, mastocytosis and IgE it has been
      difficult to consistently demonstrate a role for these effector cells/molecules
      in resistance to nematode parasites, although mast cells are clearly important in
      some cases. It therefore seems that, in general, less classical Th2 controlled
      effector mechanisms, which remain poorly defined, are probably important in
      resistance to nematode parasites. Thus, our understanding of both the induction
      and effector phases remains incomplete and will remain an intense area of
      interest in the coming years.

PMID- 9762560
TI  - Recent studies on the reproductive biology of the schistosomes and their
      relevance to speciation in the Digenea.
AB  - The members of the family Schistosomatidae, dioecious Digenea, are discussed with
      regard to their distribution, intermediate and definitive host-parasite
      relationships. The biological species concept is considered together with the
      difficulties of its application to Schistosoma spp. and the Digenea. The
      correlation between pairing of adult schistosomes, physical and sexual
      development and the maintenance of reproductive potential is emphasised.
      Development of the female reproductive system does not depend upon species
      specific pairing. In some combinations, e.g., Schistosoma haematobium/Schistosoma
      intercalatum and Schistosoma bovis/Schistosoma curassoni, a specific mate choice
      system apparently does not exist, whereas it does in other combinations, e.g.,
      Schistosoma mansoni/Schistosoma intercalatum. In mixed infections change of mate
      may occur and when the opportunity arises heterospecific pairs of worms will
      change partners to conspecific pairs. Interspecific pairing in adult schistosomes
      will lead to either hybridisation or parthenogenesis. Yet the majority of
      schistosomes that inhabit the same definitive host maintain their genetic
      identity: specific mate recognition, site selection within the host and
      heterologous immunity have been suggested as isolating mechanisms. Experimental
      intraspecific crosses have enabled evaluation of the degree to which some
      populations separated and became reproductively isolated through pre-mating
      isolating mechanisms, indicative of incipient speciation, e.g., the Lower Guinea
      and Zaire strains of S. intercalatum. The occurrence and significance of
      parthenogenesis in schistosomes and other species of Digenea are discussed. The
      consequences of interspecific mating interactions in schistosomes with regard to
      parasite epidemiology, interspecific competition and genetic heterogeneity are
      debated. Geographical isolation and host specificity represent important pre
      zygotic isolating mechanisms. It is suggested that site selection within the host
      and heterologous immunity may both reduce interspecific genetic interchange when
      digenean parasites utilise the same definitive host.

PMID- 9762561
TI  - Relative concentrations of heavy metals in the parasites Ascaris suum (Nematoda)
      and Fasciola hepatica (Digenea) and their respective porcine and bovine
      definitive hosts.
AB  - The concentrations of lead and cadmium determined by electrothermal atomic
      absorption spectrometry were significantly higher in the liver and kidney,
      respectively, of pigs than in their intestinal nematode parasites Ascaris suum.
      There was no clear pattern in the distribution of lead within the ascarids, but
      cadmium concentrations were highest in the intestine. A parallel investigation of
      cattle naturally infected with the liver fluke, Fasciola hepatica, revealed
      interesting differences. Although the cadmium content of F. hepatica was
      considerably lower than that in the tissues of cattle, the concentration of lead
      in the digenean was on average 172, 53 and 115 times higher than in the muscle,
      kidney and liver of the host. Furthermore, there was a significant positive
      correlation between the weight of individual F. hepatica and their lead burden.
      The lack of appreciable heavy-metal accumulation in A. suum is consistent with
      results for the nematode Anguillicola crassus in fish. However, although lead
      concentrations in the liver fluke F. hepatica were considerably elevated above
      host tissue levels, the degree of heavy-metal accumulation was relatively low
      when compared to that of acanthocephalans and cestodes of fish.

PMID- 9762562
TI  - Comparison of the levels of intra-specific genetic variation within Giardia muris
      and Giardia intestinalis.
AB  - The extent of intra-specific genetic variation between isolates of Giardia muris
      was assessed by allozyme electrophoresis. Additionally, the levels of allozymic
      variation detected within G. muris were compared with those observed between
      members of the two major assemblages of the morphologically distinct species
      Giardia intestinalis. Four isolates of G. muris were analysed. Three (Ad-120, 
      150, -151) were isolated from mice in Australia, while the fourth (R-T) was
      isolated from a golden hamster in North America. The 11 isolates of G.
      intestinalis (Ad-1, -12, -2, -62, representing genetic Groups I and II of
      Assemblage A and BAH-12, BRIS/87/HEPU/694, Ad-19, -22, -28, -45, -52,
      representing genetic Groups III and IV of Assemblage B) were from humans in
      Australia. Intra-specific genetic variation was detected between G. muris
      isolates at four of the 23 enzyme loci examined. Similar levels of variation were
      found within the genetic groups that comprise Assemblages A and B of G.
      intestinalis. These levels of intra-specific variation are similar to those
      observed within other morphologically-distinct species of protozoan parasites. We
      suggest that the magnitude of the genetic differences detected within G. muris
      provides an indication of the range of genetic variation within other species of
      Giardia and that this can be used as a model to delineate morphologically similar
      but genetically distinct (cryptic) species within this genus.

PMID- 9762563
TI  - Blood clotting disorders during experimental sarcocystiosis in calves.
AB  - The effects of experimental infection of calves with Sarcocystis cruzi on the
      blood coagulation cascade were investigated. Calves were inoculated orally with 1
      x 10(5) sporocysts (group S1, n = 6) or with 5 x 10(5) sporocysts of S. cruzi
      (group S2, n = 3). A group of eight calves served as non-infected controls (group
      C). The animals were bled once during the first 4 weeks of infection and twice a
      week thereafter until day 40 p.i. The following parameters were measured:
      activated partial thromboplastin time, prothrombin time, thrombin time, reptilase
      time, thrombin coagulase time, factors XII, XI, X, IX, VIII:C, VII, V,
      prekallikrein, fibrinogen, alpha 2-antiplasmin, antithrombin III, alpha 1
      antitrypsin, alpha 2-macroglobulin, haematocrit, haemoglobin, numbers of
      erythrocytes and thrombocytes. The infected calves developed acute sarcocystiosis
      from 25 (S1) or 29 (S2) days p.i. onwards. During the acute disease,
      antiproteases tended to elevated values and thrombocyte counts were generally
      reduced. In group S1 prolonged prothrombin time and reduced activities of factors
      VII or V were found. In group S2 accelerated prothrombin time and activated
      partial thromboplastin time, as well as elevated factor X activities, were
      recorded even before the onset of clinical disease at 19 days p.i. While
      prothrombin time returned to normal levels thereafter, activated partial
      thromboplastin time remained short. Activities of factor V, factor VII and factor
      X were significantly reduced in group S2 at the onset of acute sarcocystiosis,
      and one of the three calves died at 29 days p.i. The other parameters were not
      significantly affected by either dose of infection. No evidence for a classical
      disseminated intravascular coagulation syndrome could be found; however, it was
      demonstrated that S. cruzi alters plasma coagulation in a dose-dependent way.

PMID- 9762564
TI  - Incompatibility of Protopolystoma xenopodis (Monogenea: Polystomatidae) with an
      octoploid Xenopus species from southern Rwanda.
AB  - Protopolystoma xenopodis is an oviparous monogenean occurring as an adult in the
      urinary bladder of the clawed toad Xenopus laevis. Oncomiracidia invade the
      host's kidneys where juveniles develop, subsequently migrating to the definitive
      site. In central Africa, the tetraploid X. laevis occurs in sympatry with
      octoploid congeners, including Xenopus wittei, believed to be the hybrid
      derivatives of X. laevis- and Xenopus fraseri-like parental lineages. Twenty
      laboratory-raised, naive specimens of an X. wittei-like species from southern
      Rwanda were each exposed to 30 embryonated P. xenopodis eggs (at 20 degrees C)
      and screened for parasite egg production until 9 months post-exposure. These
      toads failed to support the development of gravid parasites (comparable
      experimental procedures produce at least 35% prevalence of patent infection in
      the natural host X. laevis). Further X. wittei aff. (n = 26) and X. laevis (n =
      17) were exposed to P. xenopodis oncomiracidia and dissected at variable times
      post-exposure: larvae were able to invade the kidneys of X. wittei aff. and began
      feeding and morphological development. Severe mortality of juveniles occurred in
      both natural and unnatural hosts between invasion and 39 days post-exposure.
      However, while small numbers of parasites persisted in X. laevis, no stages were
      found in X. wittei aff. beyond 39 days. Present data demonstrate the
      incompatibility of P. xenopodis with X. wittei aff. and are consistent with a
      hypothesis that specificity in Protopolystoma-Xenopus systems is determined
      primarily by the ability of juveniles to complete development in the host's
      kidneys.

PMID- 9762565
TI  - Reproductive interference in concurrent infections of two Protopolystoma species
      (Monogenea: Polystomatidae).
AB  - The prevention of interspecific reproductive interference is one possible
      explanation for spatial niche divergence between congeneric monogeneans. However,
      there is little direct evidence that reproductive interactions with other species
      are potentially deleterious to the majority of parasitic platyhelminths. Xenopus
      fraseri-like clawed toads from lowland rainforest in eastern Democratic Republic
      of Congo are infected by two species of polystomatid monogenean, Protopolystoma
      fissilis and Protopolystoma ramulosus. Both occur as adults in the host urinary
      bladder, and exhibit identical copulatory structures and similar body sizes. The
      small area of the habitat in relation to parasite body size makes close proximity
      inevitable in concurrent infections. Eggs were collected from five naturally
      infected hosts: two of these harboured concurrent infections, and three were
      infected with P. fissilis only. Eggs from concurrent infections showed reduced
      viability (57.6% embryonation, n = 413) compared with those from P. fissilis-only
      infections (85.2%, n = 439). This effect may be due to some form of reproductive
      interference, possibly failure to develop following interspecific cross
      fertilisation.

PMID- 9762566
TI  - Viable Cryptosporidium parvum oocysts exposed to chlorine or other oxidising
      conditions may lack identifying epitopes.
AB  - The intestinal protozoan parasite Cryptosporidium parvum is a known cause of
      water-borne disease in humans. The detection of Cryptosporidium oocysts in water
      samples relies upon the use of fluorescently labelled antibodies, preferably
      using flow cytometry and epifluorescence microscopy. Here we demonstrate that
      four commercially available antibodies recognise a similar set of immunodominant
      epitopes on the oocyst wall. These epitopes appear to be carbohydrate in nature
      and are labile to chlorine treatment and oxidising conditions. Sodium
      hypochlorite and sodium meta-periodate reduced the ability of the antibodies to
      detect Cryptosporidium oocysts. Damage to the epitopes did not necessarily reduce
      the viability of oocysts. This finding may be important for the water industry,
      where naturally occurring oxidising conditions or sanitizing treatments could
      produce viable oocysts that are undetectable using standard protocols.

PMID- 9762567
TI  - A comparison of three different dihydroartemisinin formulations for the treatment
      of acute uncomplicated falciparum malaria in Thailand.
AB  - We compared the safety and efficacy of three formulations of dihydroartemisinin
      for the treatment of acute uncomplicated falciparum malaria in patients who
      received a total dose of 600 mg dihydroartemisinin over 5 days. The first group
      was treated by dihydroartemisinin produced and formulated in the People's
      Republic of China, the second group was treated by dihydroartemisinin produced in
      Vietnam but formulated by the Government Pharmaceutical Organization of Thailand
      and the third group was treated by dihydroartemisinin produced and formulated by
      the Government Pharmaceutical Organization of Thailand. All patients were
      admitted to hospital to evaluate safety and efficacy for a total of 28 days. By
      the third day of treatment, most patients were blood-smear negative for parasites
      and none had serious adverse effects. Minor symptoms such as nausea, dizziness
      and headache were similar in the three groups and disappeared after 3 days of
      treatment. One-hundred and thirty-three patients completed the 28-day follow-up
      period. The cure rates of groups I, II and III were 80%, 85% and 92%,
      respectively (P > 0.02). There were no significant differences in fever clearance
      or parasite clearance among the three groups. We conclude that the three
      formulations of dihydroartemisinin produced and formulated in different countries
      were safe and effective in treating uncomplicated falciparum malaria acquired in
      Thailand.

PMID- 9762568
TI  - Sequence analysis of the major piroplasm surface protein gene of benign bovine
      Theileria parasites in east Asia.
AB  - Relatively benign Theileria parasites are widespread among cattle in East Asia.
      Although the parasites are presumed to be of the Theileria sergenti/Theileria
      buffeli/Theileria orientalis group, their taxonomic status and epidemiology have
      not been well defined. In the present study, theilerial DNA samples were
      collected from various East Asian countries, including Japan, Korea, Taiwan, and
      China. DNA sequences encoding a major piroplasm surface protein were amplified by
      polymerase chain reaction, followed by cloning into a plasmid vector. More than
      20 DNA clones derived from parasite DNA of a single infected animal were examined
      for their restriction-fragment-length polymorphism, showing that they were
      classified into four major types. Sequence analysis revealed six types of DNA
      sequences encoding major piroplasm surface protein with homologies of between 75
      and 91%. Of the six sequences, four were identical to those previously reported,
      while the other two appeared to be new sequences. Among the DNA clones derived
      from a single infected animal, two to three distinct sequences were often found.
      Phylogenetic analysis of the six major piroplasm surface protein sequences
      indicates that five of the six are closely related to each other, and that all
      are distantly related to the homologous genes of Theileria annulata and Theileria
      parva. The results suggest that, in addition to those described as T. sergenti/T.
      buffeli/T. orientalis, there may be some undefined Theileria species distributed
      in East Asia, and that many cattle are infected with mixed populations of
      geographically variable Theileria parasites.

PMID- 9762569
TI  - In vitro expression of a recombinant paramyosin of Ancylostoma caninum.
AB  - The objective of this study was to characterise a recombinant antigen of
      Ancylostoma caninum that had been identified by immunoscreening with selected
      antisera described elsewhere. In vitro expression of clone 341 produced a protein
      with an apparent molecular mass of approximately 34 kDa which was recognised in
      Western blots by antisera against whole worms and antisera against esophagi from
      adult worms, but not by sera from experimentally infected dogs or rabbits. DNA
      sequencing showed a cDNA of 1176 bp coding for a 34-kDa protein, similar to the
      size identified in the immunoblot. DNA database comparison revealed an 80-82%
      homology with the Caenorhabditis elegans unc-15 gene coding for paramyosin. The
      deduced aa sequence of clone 341 showed 95% homology with the paramyosin aa
      sequence of C. elegans. Affinity purified antibodies against the recombinant
      protein recognise a protein with an apparent molecular mass of 97 kDa of A.
      caninum muscle tissue fraction which is in accordance with the molecular mass of
      paramyosin from Schistosoma mansoni and Schistosoma japonicum.

PMID- 9762570
TI  - Use of P-glycoprotein gene probes to investigate anthelmintic resistance in
      Haemonchus contortus and comparison with Onchocerca volvulus.
AB  - A P-glycoprotein gene probe from the sheep parasitic nematode Haemonchus
      contortus was developed and used to analyse restriction fragment length
      polymorphisms between susceptible isolates and isolates resistant to either
      benzimidazole; levamisole and benzimidazole; or benzimidazole, ivermectin and
      closantel. No polymorphism could be correlated with any of the different
      resistances. A P-glycoprotein gene probe was also isolated from the human
      nematode parasite Onchocerca volvulus and an Onchocerca-specific PCR was
      developed.

PMID- 9762571
TI  - The phylogenetic position of Udonella (Platyhelminthes).
AB  - Phylogenetic analysis of molecular data from complete 18S rRNA and partial 28S
      rRNA genes, of a variety of platyhelminths, places the enigmatic Udonella
      caligorum firmly as a monopisthocotylean monogenean. Both maximum parsimony and a
      modified distance measure, operating under a maximum likelihood model, gave
      identical solutions for each data set. These data further support morphological
      evidence from ultrastructural studies indicating the neodermatan affinities of
      Udonella, namely shared features in sensory receptors, surface tegument, sperm
      structure and spermiogenesis. The molecular data reject the class Udonellidea and
      the placement of udonellids as sister-group to the Neodermata. As shown
      previously with molecular data, the monogeneans appear as a paraphyletic
      assemblage comprising strongly monophyletic Monopisthocotylea and
      Polyopisthocotylea. Their relationships with the trematodes and cestodes are not
      resolved with 28S rDNA or 18S rDNA alone.

PMID- 9762572
TI  - A comparison of the first internal transcribed spacer of ribosomal DNA in seven
      species of Trichostrongylus (Nematoda: Trichostrongylidae).
AB  - The first internal transcribed spacer (ITS-1) of the ribosomal DNA of seven
      species of Trichostrongylus was sequenced. The length of ITS-1 in the different
      species varied from 387 to 390 bases. The G + C content of the ITS-1 sequences
      were approximately 42%. Little or no intraspecific variation was detected in the
      three species. Trichostrongylus axei, Trichostrongylus colubriformis and
      Trichostrongylus vitrinus, for which multiple isolates from different
      geographical regions were sequenced. In contrast, the level of ITS-1 sequence
      differences between species ranged from 1.3% to 5.7%. The greatest sequence
      differences were detected between T. tenuis, the parasite species which infects
      birds and the six species found in mammals. Some of the nucleotide differences
      occurred at sites corresponding to recognition sites for restriction
      endonucleases. These results are compared with previous data obtained for the
      second internal transcribed spacer (ITS-2). The ITS-1 data indicate that this
      region of rDNA may also be useful for systematic studies in trichostrongylid
      nematodes.

PMID- 9762573
TI  - Phylogeny of benign Theileria species from cattle in Thailand, China and the
      U.S.A. based on the major piroplasm surface protein and small subunit ribosomal
      RNA genes.
AB  - The major piroplasm surface protein and small subunit ribosomal RNA genes of
      benign Theileria species isolated from cattle in China, Thailand and the U.S.A.
      were amplified by polymerase chain reaction, cloned and sequenced. The major
      piroplasm surface protein genes of these three isolates were more than 89%
      identical at amino-acid level. Several deletions in the gene from the Thai
      isolate led to considerable structural change through frame shifts of the major
      piroplasm surface protein. Phylogenetic analyses based on both of the major
      piroplasm surface protein and small subunit ribosomal RNA genes suggest that
      there may be a second cosmopolitan benign Theileria species infecting cattle in
      addition to the Theileria sergenti/buffeli/orientalis complex.

PMID- 9762574
TI  - Protein supplementation improves the performance of parasitised sheep fed a straw
      based diet.
AB  - A study was made of the benefits of protein supplementation for parasitised and
      non-parasitised lambs. Sixty, 5-month-old crossbred wether lambs were placed in
      individual pens indoors for 9 weeks. Half of the animals were experimentally
      dosed with 1500 Haemonchus contortus larvae per head per week and were fed ad
      libitum and the other half were worm-free, pair-fed controls. Diets were
      formulated to be iso-energetic (9.0 MJ of calculated metabolisable energy per kg
      dry matter) with five levels of protein (10, 13, 16, 19 and 22% crude protein).
      These diets were based on oaten chaff, with barley, cotton-seed meal, urea and
      mineral mix (except for the 22% crude protein diet which did not contain barley).
      Dietary crude protein content increased live-weight gain, feed intake, rumen
      fluid ammonia-N, packed cell volume, eosinophil counts and antibody responses to
      H. contortus L3 antigen and decreased faecal worm egg counts significantly.
      Infection did not significantly affect packed cell volume of animals on diets
      with 16, 19 and 22% crude protein content. We conclude that extra dietary protein
      can prevent the adverse effects of H. contortus infection on animal production.

PMID- 9762575
TI  - In vitro antifilarial activity of organometallic complexes against infective
      larvae of Molinema dessetae and adult females of Brugia pahangi.
AB  - New organometallic complexes having protozoocidal properties were evaluated for
      their in vitro antifilarial activity using two models: infective larvae of
      Molinema dessetae and adult females of Brugia pahangi. The compound most active
      on the M. dessetae model was Ir(I)-COD-pentamidine tetraphenylborate with an EC50
      = 6 +/- 1 microM after 7-day-incubation. In the 2-aminobenzothiazole series,
      Ruthenium was more potent than Iridium for antifilarial activity. A
      dithiocarbamate function significantly enhanced the antifilarial activity. The
      compounds derived from benzimidazole were inactive whatever the metal (Iridium or
      Rhodium). The other compounds exhibited EC50 ranging from 10 to 31 microM. On
      adult female Brugia pahangi in vitro, Pt-DDH-N-acetylleucine, Pt-diminazene and
      Pd-Cl4-piperazine at 20 microM began to kill both microfilariae and the
      developing embryos within the mothers on day 2. The compounds, except for Pd-Cl4
      piperazine, killed the adults after 5 days. Rh-Cl-2-chloropyridine caused obvious
      slowing of the adults from day 3 onward but did not affect the viability of
      adults, microfilariae or developing embryos. In vivo antifilarial investigations
      are necessary to appreciate the real advantage of heavy metal complexes in the
      experimental treatment of filariasis.

PMID- 9762576
TI  - Rodent malaria prophylaxis by transdermal delivery of primaquine.
AB  - The efficacy of a new transdermal delivery system of primaquine in order to
      obtain causal prophylaxis against sporozoite-induced Plasmodium yoelii infection
      was evaluated. A single administration of a 1.0 cm2 transdermal delivery system
      containing 5.0 mg of primaquine was able to protect 100% of treated mice. This
      result suggests that the transdermal route may be a very interesting approach for
      malaria prophylaxis and should encourage further studies in order to determine
      the absolute bioavailability of the drug as well as its dose-effect relationship.

PMID- 9762577
TI  - Seasonal variation of gastrointestinal nematodes of sheep in the region of
      Joannina, Greece.
AB  - Parasitological and growth studies on two groups of naturally infected sheep,
      with or without anthelmintic treatment, from the age of 3 months to 2 years were
      carried out in the region of Joannina, Greece. A split-plot design was used so
      that each group, consisting of seven pure-bred Boutsiko and seven cross-bred
      Boutsiko with Karamaniko (F1) lambs, grazed separate parasitologically equivalent
      pasture plots. Faecal egg counts, pasture larval counts, plasma pepsinogen levels
      and live weight were recorded monthly. Infective larvae on each pasture plot
      increased during autumn and winter. Mean faecal egg counts for strongyle-type
      eggs were higher in the non-treated than the treated group and in the cross than
      the pure-bred sheep. Mean plasma pepsinogen levels were higher during autumn of
      the second year of the study. The results of the study suggest that the factors
      affecting the epidemiology of gastrointestinal nematodes of naturally infected
      sheep during grazing in the region of Joannina include anthelmintic treatment,
      host genotype and season, while the effectiveness of anthelmintic treatment in
      this study, as applied in the area, was questionable.

PMID- 9762578
TI  - Canine neosporosis: clinical signs, diagnosis, treatment and isolation of
      Neospora caninum in mice and cell culture.
AB  - Clinical signs, diagnosis, treatment and isolation of Neospora caninum from two
      littermate dogs are described. Three of six pups from a Labrador bitch developed
      paralysis. Neosporosis was diagnosed ante mortem by serological examination in
      two of the affected pups. At necropsy, tissue cysts were seen in unstained smears
      and in histologic sections of their brains. Tissue cysts were often thin-walled
      (approximately 1 micron) but antigenically and ultrastructurally identified as N.
      caninum. Furthermore, N. caninum (isolates NC-4, NC-5) was isolated in mice and
      in cell cultures inoculated with neural tissues of these two dogs. Serological
      diagnosis of neosporosis using a variety of tests is discussed.

PMID- 9762579
TI  - Monoclonal antibodies to Toxoplasma gondii strain 119 identify recently isolated
      Danish strains as one group.
AB  - Four mAb raised against the Danish Toxoplasma gondii strain 119, were selected by
      screening hybridoma supernatants by indirect immunofluorescence against
      tachyzoites of the RH strain in order to obtain strain-restricted markers. Strain
      restriction extended beyond discrimination of the 119 and RH strains, as
      demonstrated on a further six T. gondii reference strains [BK and GT1 (group A),
      NTE and 561 (group B), and NED and C56 (group C)]. The bradyzoite-specific mAb,
      4.3, reacted to the GT1, NTE and 561 strains, but not to the BK, NED or C56
      strains. The tachyzoite-specific mAb, 4.25, reacted to all strains tested except
      the RH strain, while mAb 5.1 reacted to tachyzoites of strains NTE and 561, but
      not to those of the BK, GT1, NED or C56 strains. Monoclonal antibody 5.15 reacted
      with the same strain restriction as monoclonal antibody 5.1, but to bradyzoites
      as well as tachyzoites. A T. gondii strain collection representative for a small
      geographic area (Denmark) was established within a short time span from a variety
      of animal species. Using the mAb as typing reagents to this Danish strain
      collection, all 36 animal and two human strains were identified as having the
      same reaction pattern as strains 119, NTE and 561.

PMID- 9762580
TI  - Prenatal protein restriction alters synaptic mechanisms of callosal connections
      in the rat visual cortex.
AB  - Mild prenatal protein malnutrition, induced by reduction of the casein content of
      the maternal diet from 25 to 8%, calorically compensated by the addition of
      excess carbohydrates, leads to so-called "hidden" malnutrition in the rat. This
      form of malnutrition results in normal body and brain weights of pups at birth,
      but in significant alterations of their central nervous system neurochemical
      profiles. Since severe forms of prenatal malnutrition induce morpho-functional
      deficits on callosal interhemispheric communication together with brain
      neurochemical disturbances, we evaluated, in rats born from mothers submitted to
      an 8% casein diet, the potassium-induced release of [3H]-noradrenaline in visual
      cortex slices, as well as functional properties of callosal-cortical synapses by
      determining cerebral cortical excitability to callosal inputs and fatigability
      and temporal summation of transcallosal evoked responses. Rats born from mothers
      submitted to a 25% casein diet served as controls. At birth prenatally
      malnourished pups had significantly higher cortical percent net noradrenaline
      release (14.79 +/- 1.11) than controls (9.14 +/- 1.26). At 45-50 days of age,
      rehabilitated previously malnourished rats showed, when compared to controls; (i)
      significantly reduced percent net noradrenaline release in the visual cortex
      (4.50 +/- 0.52 vs 11.31 +/- 1.14); (ii) decreased cortical excitability to
      callosal inputs as revealed by significantly increased chronaxie (607.2 +/- 82.8
      microseconds vs 351.3 +/- 47.7 microseconds); (iii) enhanced fatigability of
      transcallosal evoked responses as revealed by significantly decreased stimulus
      frequency required to fatigate the responses (4.9 +/- 0.8 Hz vs 9.2 +/- 1.3 Hz);
      and (iv) decreased ability of callosal-cortical synapses to perform temporal
      summation, as revealed by significantly reduced percent response increment to
      double-shock (54.2 +/- 6.2 vs 83.0 +/- 11.0, for a 3.2-ms interstimulus time
      interval). These changes, resulting from mild prenatal protein restriction, are
      discussed in relationship to developmental processes leading to the formation of
      synaptic contacts between callosal axons and their appropriate cortical target
      during perinatal age.

PMID- 9762581
TI  - Morphological and morphometrical changes in dorsal root ganglion neurons
      innervating the regenerated lizard tail.
AB  - The variations occurring in neurons from dorsal root ganglia that provide
      innervation to the regenerated tail of the lizard (vicarious ganglia) are
      analysed. Vicarious ganglion neurons, when compared to control ganglion neurons
      (i.e. ganglia from the same animal that were not involved in the reinnervation
      process), show a size increase of the soma (cell hypertrophy) which applies to
      all cell types and subtypes. No statistically significant differences in the
      relative percentage of neurofilament-poor (type D) and neurofilament-rich (type
      L) neurons were found between vicarious dorsal root ganglia compared to controls
      in all animals. On the contrary, within L neuron sub-types, a statistically
      significant increase in sub-type L2 (very rich in neurofilaments), and the
      appearance of sub-type L3 neuron which is not detectable in controls, were
      demonstrated in vicarious dorsal root ganglia. In spite of these variations in
      size and percentage distribution, no structural and ultrastructural differences
      of the various cell types and sub-types are detectable, except for the appearance
      of the sub-type L3 neurons. However, this neuron sub-type might not be considered
      specific of hypertrophy since the same morphological features have been observed,
      in normal conditions, in lizard dorsal root ganglia from cervical and lumbar
      spinal levels that provide innervation to limb plexuses.

PMID- 9762582
TI  - Endogenous modulators of brain Na+,K(+)-ATPase at early postnatal stages of rat
      development.
AB  - The presence of endogenous modulators (peaks I and II) of synaptosomal Na+, K(+)
      ATPase activity from adult rat cerebral cortex was previously suggested. In this
      study, the presence of such modulators at different postnatal stages of rat
      development was examined and their effect was tested on Na+, K(+)-ATPase
      activity. Synaptosomal membrane Na+, K(+)-ATPase activity was enhanced 20-30% by
      peak I and inhibited 70-75% by peak II obtained from 4-, 10-, 20- and 35-40-day
      old rats. A fraction purified from peak II by anionic exchange HPLC (termed II-E)
      highly inhibits enzyme activity and behaves as a ouabain-like factor. Inhibitory
      activity of a 4-day-old II-E fraction proved higher than the corresponding
      fraction obtained from adult rats. Since expression of cerebral Na+, K(+)-ATPase
      has been shown to increase 10-fold during development whereas peak II
      concentration was observed to remain constant, and given the higher potency of
      purified neonatal II-E fraction, the effect of the latter may be greater at early
      postnatal stages of development than during adult life. It is suggested that the
      II-E fraction, which contains an ouabain-like factor, may play a role in neuronal
      development.

PMID- 9762583
TI  - Arachidonate transport through the blood-retina and blood-brain barrier of the
      rat after reperfusion of varying duration following complete cerebral ischemia.
AB  - The permeability-surface area product (PS) of [1-14C]arachidonate at the blood
      retina and blood-brain barrier was determined by short carotid perfusion in young
      Wistar rats 1 or 6 h after recovery period following complete cerebral ischemia
      induced by temporary cardiac arrest. For the retina and structures of visual
      system, hypothalamus and olfactory bulb there was no significant difference over
      sham-operated rats among mean PSs. For cortex, hippocampus and striatum,
      significant increases were found at both time intervals of recovery after cardiac
      arrest. The ischemia-reperfusion model was characterized by a significant
      increase in tissue conjugated diene in the hippocampus and microsomal
      lysophosphatidylcholine acyltransferase activity in the cortex. Consistent with
      these findings, we also show ultrastructural evidence mainly represented by
      partial opening of interendothelial junctions and mild signs of tissue edema in
      surrounding neuropil, suggesting barrier leakiness predominantly in the cortex,
      hippocampus and striatum but almost absent in the retina microvessels. Our
      results indicate that ischemia-reperfusion does affect influex through blood
      brain barrier into regional structures of rat central nervous system of
      arachidonate, a metabolic substrate and lipid mediator rapidly incorporated into
      microcapillary and brain lipids. The data also suggested that: (i) reactive
      oxyradicals were moderately generated during the early phase of ischemic
      reperfusion process in the rat; (ii) after reperfusion, in vitro susceptibility
      of different brain regions to iron-induced peroxidation was highest in the
      hippocampus and lowest in the cortex and striatum; (iii) membrane phospholipid
      repair mechanisms were activated at the same time.

PMID- 9762584
TI  - Differences in myelination between spinal cord and corticular tissue transplanted
      intraocularly in rats.
AB  - This paper compares the myelination in rat cortex and spinal cord transplanted on
      the embryonic day (E) 12, 14, 16, 18, 20 and right after birth (P0) into the
      anterior eye chamber of adult rats. Myelinated fibers were not observed in either
      cortical or spinal cord transplants of E12. When transplanted on E14, abundant
      myelinated fibers developed in the spinal cord and gathered at the periphery of
      the transplants as a "white matter". In the grafted cortex myelinated fibers were
      found when transplantation occurred on E16 or later. The myelinated fibers,
      however, remained scarce or formed only narrow bundles. The number and
      distribution of myelinated fibers did not depend on the donor's age between E16
      and P0: even in the latter case transplanted cortex were found without
      myelination. The differences could be attributed to the different development of
      the cortical and spinal cord oligodendrocytes and to the different intrinsic
      organization of the grafted samples.

PMID- 9762585
TI  - Developmental regulation of mouse brain monomeric acetylcholinesterase.
AB  - Acetylcholinesterase (AChE) molecular forms were studied during mouse brain
      development. Mouse embryos expressed a monomeric (G1) and a tetrameric (G4) AChE
      form. Our results indicate that G4 AChE expressed at embryonic day (ED) 9 and
      ED15 could be purified by acridinium-Sepharose chromatography and shared similar
      biochemical and kinetic properties with the adult form. However, the G1 form
      expressed at either embryonic stage did not bind to acridinium, was not inhibited
      by excess substrate, and possessed higher K(m) and lower Vmax values than the
      adult G1 form. Two peripheral anionic binding site inhibitors, fasciculin and
      propidium, had a significantly lower affinity for the monomeric form at ED9.
      Results are discussed in terms of the biological significance of the embryonic G1
      form, and its resemblance to the AChE activity found, associated with the senile
      plaques present in the brains of Alzheimer's patients.

PMID- 9762587
TI  - The real and imagined harmful effects of rewards: implications for clinical
      practice.
AB  - In recent years, a number of researchers and social critics have cautioned
      against the widespread application of behavioral interventions on the grounds
      that the philosophy of behaviorism is fundamentally manipulative and damaging to
      creative and intrinsically motivated behavior. Most central to their arguments
      are concerns about the harmful effects of "extrinsic" rewards. Though concerns
      about the allegedly harmful effects of "rewards" on intrinsically motivated
      actions may have been partially allayed by a recent meta-analysis, proponents of
      the view that intrinsic interest is eroded by the delivery of contingent rewards
      will likely continue to attest to the dangers of operant conditioning and its
      application to human behavior. The present manuscript addresses the content of
      claims about the harmful effects of extrinsic rewards. While consideration is
      given to the existing behavior therapy literature and its treatment of "natural"
      versus "arbitrary" rewards, some surprising convergences between the views of
      self-determination theorists and behavioral practitioners are noted.

PMID- 9762586
TI  - Brain-derived neurotrophic factor stimulates neurite outgrowth in a calretinin
      enriched neuronal culture system.
AB  - A calretinin enriched cell culture system which comprised approximately 40% of
      the total neuronal population of the E14 rat embryo was established from the
      region of the thalamic eminence (TE), and the effects of several neurotrophins on
      the neurite growth of calretinin-immunoreactive (CR-IR) neurons was investigated.
      A 4-day treatment of BDNF significantly increased the ratio of CR-IR to
      microtubule-associated protein 2-immunoreactive neurons at concentrations between
      50 and 250 ng/ml. IGF-I at 100 ng/ml and TGF-alpha at 250 ng/ml also increased
      this ratio. None of the neurotrophins examined increased the number of primary
      neurites. BDNF did, however, increase the number of secondary neurites. BDNF
      treated primary and secondary neurites were also significantly longer than
      neurites from neurons in control cultures. IGF-I elicited an increase in primary
      neurite length, but did not affect either number or length of secondary neurites.
      TGF-alpha had no effect on either number or length of the primary and secondary
      neurites. These results indicate that the maturation and development of CR-IR
      neurites is specifically affected by BDNF. It is suggested that BDNF increases
      the CR concentration above the threshold of detection by immunohistochemistry in
      cells and stimulates the sprouting of secondary CR-IR neurites.

PMID- 9762588
TI  - Generalized anxiety disorder in dysfunctional families.
AB  - The purpose of this study was to investigate the relation between persistent
      prolonged dysfunction in parents and the development of Generalized Anxiety
      disorder (GAD). Initially, 940 adult subjects from a general practice were
      studied. Thirty-two parents aged 24 to 61 yr diagnosed with GAD served as the
      experimental group, while 117 healthy normal parents aged 24-66 yr made up the
      control group. The rate of dysfunctional families with parents diagnosed with GAD
      was significantly higher than in families with parents not diagnosed with GAD.
      Family dysfunction was associated with parents' age both in men and in women. GAD
      was not connected with (1) parents' age, (2) education, (3) employment, (4)
      country of origin or (5) number of children in the family. There was no
      significant difference between men and women in onset and duration of GAD.
      Implications for diagnostic and treatment issues are discussed.

PMID- 9762589
TI  - Emotional response at the time of a potentially traumatizing event and PTSD
      symptomatology: a preliminary retrospective analysis of the DSM-IV Criterion A-2.
AB  - DSM-IV added an emotional response component to the definition of Criterion A for
      PTSD. The present study investigated the relationship between retrospective
      reports of emotional responses (fear, helplessness, and horror) and disrupted
      emotional responses ("numbing") at the time of a potentially traumatizing event
      and reports of PTSD symptomatology among undergraduate participants. We found
      that, of the DSM-IV criteria, only helplessness was significantly correlated with
      post-traumatic symptomatology. Reports of peritraumatic emotional numbing
      uniquely predicted subsequent PTSD symptomatology beyond coincident emotional
      responses, suggesting that further research is needed to explore the various
      dimensions of peritraumatic emotional response relevant to the development of
      PTSD.

PMID- 9762590
TI  - Making sense of schizophrenic symptoms; delusional statements and behavior may be
      functional in purpose.
AB  - The present paper describes the use of a functional analysis in attempting to
      make sense of symptomatic delusional statements and behaviors that people
      diagnosed with schizophrenia present. The three categories that are used to
      classify symptoms are: (1) positive reinforcement function, (2) negative
      reinforcement function, and (3) mislabeling of private events. The paper presents
      a number of clinical cases whose symptoms are representative of each category.
      Each case is then functionally treated as a result of its "category"
      characteristics, thus basing treatment on the hypothesized function (or reason)
      for the symptom.

PMID- 9762591
TI  - A review of behavioral and pharmacological treatments for habit disorders in
      individuals with mental retardation.
AB  - This paper reviews the prevalence and behavioral and pharmacological treatment
      outcome studies for habit disorders exhibited by individuals with mental
      retardation. The treatment-outcome studies target the habit disorders identified
      previously by researchers including nervous habits (nail biting, bruxism, and
      trichotillomania), motor and vocal tics, and Tourette's disorder. The paucity of
      behavioral treatments and the lack of controlled pharmacological research
      warrants further experimental evaluation of treatments for habit disorders
      affecting individuals with mental retardation. Conclusions and recommendations
      for future research are made.

PMID- 9762592
TI  - The evaluation of heart rate biofeedback using a multi-element design.
AB  - This experiment used the integration of a multi-element design with a second
      baseline to isolate the effect of biofeedback on the control of a target
      response, heart rate. The results of the experiment indicate that contingent
      visual heart rate feedback was instrumental in specifically facilitating the
      control of heart rate and that control was not mediated by the effects of changes
      in overall arousal level as measured by skin conductance. These results encourage
      the experimental analysis of biofeedback using single case designs. Further, the
      design presented herein offers a clinically and experimentally useful methodology
      for biofeedback research.

PMID- 9762593
TI  - Behavioral treatment of obsessive-compulsive disorder in African Americans:
      clinical issues.
AB  - African Americans with obessive-compulsive disorder are underrepresented in
      behavioral treatment outcome studies. This paper consists of a clinical
      discussion of issues arising during the treatment with exposure plus response
      prevention of two African-American women with obessive-compulsive disorder.
      Clinical issues, such as excessive shame, insanity fears, and a sense of
      uniqueness, complicated the treatment process. However, both clients made
      significant improvement as assessed by behavioral testing, target ratings and the
      Yale-Brown Obsessive-Compulsive Scale.

PMID- 9762594
TI  - Two-phase treatment of panic disorder and posttraumatic stress disorder with
      associated personality features resulting from childhood abuse: case study.
AB  - The treatment of a women diagnosed with panic disorder with Agoraphobia and
      posttraumatic stress disorder and maladaptive personality features resulting from
      childhood sexual and physical abuse is described. The treatment consisted of nine
      sessions of cognitive behavior therapy (CBT) for Panic Disorder with Agoraphobia
      and nine sessions of implosive therapy (IT) for Posttraumatic Stress Disorder.
      CBT decreased scores on the clinical scales of the Personality Assessment
      Inventory (PAI), but did not reduce revised Impact of Event Scale (IES) scores,
      or Dimensional Assessment of Personality Problems-Basic Questionnaire (DAPP-BQ).
      IT decreased scores on the IES and the DAPP-BQ, and further reduced scores on the
      PAI. The results are discussed with regard to Levis' (1985) implosive theory of
      psychopathology, which suggests that psychopathology can be explained by
      Pavlovian conditioning of serial cues and instrumentally conditioned avoidance
      responses.

PMID- 9762595
TI  - Dismantling simplified regulated breathing: a case of a bilingual stutterer.
AB  - In this case study of a 28-year-old bilingual male, the Simplified Regulated
      Breathing treatment for stuttering was further dismantled. Implementing
      noncontingent diaphragmatic breathing in one treatment session, stuttering was
      reduced in both English (his second language) and Russian (his native language),
      while his words per minute increased. In addition, the implementation of
      treatment resulted in a decrease in secondary struggle behaviors associated with
      stuttering. The results were seen as socially valid and the treatment was seen as
      acceptable to the participant. Implications of this case study are presented.

PMID- 9762596
TI  - Neonatal onset in fatty acid oxidation disorders: how can we minimize morbidity
      and mortality?

PMID- 9762597
TI  - Diagnosis of isovaleric acidaemia by tandem mass spectrometry: false positive
      result due to pivaloylcarnitine in a newborn screening programme.
AB  - Tandem mass spectrometric analysis of acylcarnitines and amino acids has been
      applied in newborn screening programmes for the detection of several inborn
      errors of metabolism. We report a false positive result for isovaleric acidaemia
      in a newborn screening programme using this method. The newborn screening sample
      showed a very prominent signal corresponding to the mass of isovalerylcarnitine.
      Repeat samples (age 6 days) of blood and urine showed similar results. However,
      urine organic acids were normal. Acylcarnitine analysis in blood, breast milk and
      urine of the mother also showed a prominent signal of the same mass. Gas
      chromatography-mass spectrometry of the methyl esters demonstrated that the
      signal in the patient's urine was due to the presence of pivaloylcarnitine, which
      is isomeric with isovalerylcarnitine. The patient's mother was receiving an
      antibiotic containing a derivative of pivalic acid to treat a urinary tract
      infection. Follow-up samples in the patient and the mother confirmed a decrease
      in the levels of pivaloylcarnitine, concomitant with the discontinuation of the
      treatment. We conclude that pivaloylcarnitine can give a false positive result
      for isovaleric acidaemia in newborns whose mothers are on treatment with
      pivoxilsulbactam-containing antibiotics.

PMID- 9762598
TI  - Variable clinical presentation in three patients with 3-methylglutaconyl-coenzyme
      A hydratase deficiency.

PMID- 9762599
TI  - Methylmalonic acidaemia with bilateral globus pallidus involvement: a
      neuropathological study.
AB  - A 16-month-old boy was hospitalized because of a 1-day history of severe
      ketoacidosis with lethargy, hypotonia, vomiting, and important dyspnoea. Organic
      acid assay by gas chromatography-mass spectrometry confirmed the diagnosis of
      methylmalonic acidaemia (MMA). On the sixteenth day, he developed an acute
      extrapyramidal disorder. The CT scan of the brain disclosed bilaterally symmetric
      lucency of basal ganglia. He died at 17 months of age. Post-mortem
      neuropathological examination, showed severe necrosis with spongiosis, cystic
      cavitation and numerous lipid-laden macrophages of the globi pallidi, and mild
      spongiosis of subthalamic nuclei, mammillary bodies, portion of internal capsule
      adjacent to globus pallidus, superior cerebellar peduncles and tegmentum of
      brainstem. Pallidal infarction, a focal ischaemic lesion, demonstrates that
      ischaemia/energy depletion may be important in the etiology of the neuropathology
      of MMA.

PMID- 9762600
TI  - Lactic acidosis in long-chain fatty acid beta-oxidation disorders.
AB  - Among the many disorders of fatty acid beta-oxidation known today, the disorders
      of long-chain fatty acid oxidation are the most severe and life-threatening. One
      remarkable abnormality, not observed in, for instance, medium-chain acyl-CoA
      dehydrogenase deficiency, is the moderate to severe lactic acidaemia in long
      chain fatty acid beta-oxidation-deficient patients, suggesting that oxidation of
      pyruvate is also compromised. In order to understand the underlying basis of the
      lactic acidaemia in these patients, we have studied the formation of L-lactate
      and pyruvate in cultured skin fibroblasts incubated with D-glucose. All long
      chain fatty acid beta-oxidation-deficient cell lines studied were found to show a
      moderate elevation of lactate when compared with control and medium-chain acyl
      CoA dehydrogenase-deficient fibroblasts. Interestingly, differences were found
      between cells deficient in long-chain 3-hydroxyacyl-CoA dehydrogenase and very
      long-chain acyl-CoA dehydrogenase, suggesting that saturated acyl-CoA esters and
      their 3-hydroxyacyl-CoA derivatives affect pyruvate metabolism differently.

PMID- 9762601
TI  - Hunter disease in the Spanish population: molecular analysis in 31 families.
AB  - Mucopolysaccharidosis type II (Hunter disease) is an X-linked disorder due to
      deficiency of the lysosomal enzyme iduronate 2-sulphatase. Here we report an
      update of molecular studies in 31 Spanish families with Hunter disease. We found
      a total of 22 novel small mutations (7 reported previously by our group), and 4
      large deletions or rearrangements. Particularly relevant are two mutations, one
      showing an alternatively spliced product although the normal splice site is
      conserved; the other mutation results in an amino acid change that most likely
      modifies regulation of expression of the IDS gene. Except for large gene
      alterations and for the G374sp mutation already described, we could not establish
      a clear phenotype-genotype correlation. Mutation G374sp is the point mutation
      most frequent in our population (10%) and is always associated with mild
      phenotype. Our molecular analyses carried out in a relatively large series of
      patients with Hunter disease contribute to the identification of new mutations
      and reinforce the conclusions drawn in other populations about the genotype
      phenotype correlation and the gene distribution of mutations.

PMID- 9762602
TI  - Generalized peroxisomal disorder in male twins: fatty acid composition of serum
      lipids and response to n-3 fatty acids.
AB  - Male, identical twins presented with hypotonia, hypoglycaemia, dysmorphic facies,
      feeding problems, discoloured stools, hepatomegaly, and nephrolithiasis. Elevated
      blood levels of very long-chain fatty acids and bile acids suggested a
      peroxisomal disorder. Plasmalogen biosynthesis in cultured fibroblasts was
      reduced. Morphologically distinct peroxisomes were undetectable in liver. Twin 1
      suffered from nephrocalcinosis and severe infection, and died at 18 months of
      age. Twin 2 was blind and physically severely retarded with epilepsy, but
      survived up to the age of 5 years. Studies of the fatty acid composition of serum
      lipids showed barely detectable values of eicosapentaenoic (EPA) and
      docosahexaenoic acid (DHA). During long-term treatment with these n-3 fatty
      acids, started at age 10 months, the fatty acid profile of the serum lipids was
      improved or normalized. Since n-3 fatty acids are essential elements in normal
      development, notably of the nervous system, we suggest that treatment with EPA
      and DHA should be started as early as possible in general peroxisomal disorders.

PMID- 9762603
TI  - Hyperinsulinism and hyperammonaemia.

PMID- 9762605
TI  - Complications of lysinuric protein intolerance must be treated with
      immunosuppressive drugs.

PMID- 9762604
TI  - Neonatal medium-chain acyl-CoA dehydrogenase deficiency presenting with very high
      creatine kinase levels.

PMID- 9762606
TI  - Adult-onset arginase deficiency.

PMID- 9762608
TI  - Recurrent nonimmune hydrops fetalis associated with carbohydrate-deficient
      glycoprotein syndrome.

PMID- 9762607
TI  - Anaemia and thrombocytopenia due to haemophagocytosis in a 7-month-old boy with
      galactosialidosis.

PMID- 9762609
TI  - 3-Methylglutaconic aciduria associated with hepatosplenomegaly, macrocytic
      anaemia, fever episodes, recurrent infections, cervical lymphadenopathy and
      progressive decrease of physical performance.

PMID- 9762610
TI  - A family with Leigh syndrome caused by the rarer T8993C mutation.

PMID- 9762611
TI  - Succinyl-CoA:acetoacetate transferase deficiency. Identification of a new case;
      prenatal exclusion in three further pregnancies.

PMID- 9762612
TI  - A fucosidosis patient with relative longevity and a missense mutation in exon 7
      of the alpha-fucosidase gene.

PMID- 9762614
TI  - In vivo methods useful for therapy monitoring in lactic acidosis.

PMID- 9762613
TI  - Homocystinuria (methylenetetrahydrofolate reductase deficiency) and mutation of
      factor V gene.

PMID- 9762616
TI  - MS-PCR assay to detect 677C-->T mutation in the 5,10-methylenetetrahydrofolate
      reductase gene.

PMID- 9762615
TI  - Medium-chain acyl-CoA dehydrogenase deficiency in Spain.

PMID- 9762617
TI  - The NHS is 50: the first 25 years.

PMID- 9762618
TI  - A physician's reflections on 50 years of the NHS.

PMID- 9762619
TI  - The development of public health medicine.

PMID- 9762620
TI  - The NHS: the next 50 years.

PMID- 9762621
TI  - Emerging viral diseases.

PMID- 9762622
TI  - Tuberculosis: an international perspective.

PMID- 9762623
TI  - Drug resistant tuberculosis in adults and its treatment.

PMID- 9762624
TI  - Meningitis and meningococcal septicaemia.

PMID- 9762626
TI  - Wasted words.

PMID- 9762627
TI  - Genetic counselling and testing in Europe.
AB  - The Genetic Enquiry Centre in Manchester has designed a three-pronged health
      services research programme to address current issues in genetics. The issues
      are: whether doctors who are not trained in genetics can manage the genetic
      problems they meet in their practice; whether there are enough resources in
      specialist centres to cope with current and imminent referrals; and whether
      providers of primary care recognise genetic problems and refer patients
      appropriately. The three studies providing the basis of the programme--the
      National Confidential Enquiry into Counselling for Genetic Disorders, the
      Concerted Action on Genetics Services in Europe and the Primary Care for Genetics
      Patients study--are discussed. The first two provide unique views of genetic
      counselling in the UK and of the access to and quality of health services for
      patients with or at risk of genetic disorders throughout Europe, and make
      recommendations based on their findings. The third is a continuing study that
      aims to determine the effects of patterns of referral and care in the different
      healthcare systems in Europe. Although it is unlikely that there will ever be
      enough medical geneticists to cope with the consequences of genetic advances on
      health services that are largely unprepared, specialist genetic centres are the
      natural core resource for future multi-specialty genetic services. This will give
      clinical geneticists an extended role complementary to that of diagnosing rare
      syndromes.

PMID- 9762625
TI  - Community acquired pneumonia.
AB  - CAP affects all ages but predominantly the elderly. The microbial aetiology is
      diverse and rarely established at the time of admission. Initial management
      includes assessment of severity, correction of dehydration and imbalances of gas
      exchange, and prompt administration of antibiotic. The regimens will vary by risk
      factor and severity assessment. Mortality remains high, especially in those
      requiring intensive care. Prevention includes control of underlying disease,
      smoking and ethanol abuse, and the appropriate use of influenza and pneumococcal
      vaccines.

PMID- 9762628
TI  - Reducing waiting times in lung cancer.
AB  - BACKGROUND: Concern exists over delays in the management of lung cancer patients.
      Maximum waiting times and a multidisciplinary team (MDT) approach have been
      recommended in several recent national reports. OBJECTIVE: Having implemented a
      MDT approach, we wished to assess whether national recommendations were
      achievable and to identify the major factors causing delays. METHODS: Prospective
      survey over five months of all new referrals with suspected lung cancer,
      documenting waiting times at all stages from referral to definitive treatment.
      RESULTS: Of the total of 92 patients, 57 were outpatients (67% seen within one
      week, 89% within two weeks of receipt of referral) and 35 were inpatients (all
      seen within two working days). Patient age did not influence waiting times to
      first being seen or to investigation. The result of the initial diagnostic test
      was received within two weeks of first being seen in 86% of patients. All
      patients received definitive treatment within recommended times from diagnosis.
      Delays in the early part of the care pathway were largely due to potentially
      remediable service factors, but unavoidable patient related factors were
      important in some prolonged diagnostic delays. CONCLUSIONS: National
      recommendations on waiting times are achievable in a high proportion of cases.
      The probable importance of the MDT approach is discussed.

PMID- 9762629
TI  - Comparison of the views of junior doctors, consultants and managers on work and
      training.
AB  - OBJECTIVE: To determine the views of junior hospital doctors on their working
      conditions, NHS reforms and training, and to compare their views with those of
      consultants and managers. SUBJECTS: A questionnaire was distributed to 52 junior
      doctors, 19 consultants and 14 middle or senior grade managers in an acute NHS
      trust. CONCLUSIONS: Junior doctors had strong feelings about several areas
      covered in the questionnaire; in particular, more structured training without the
      requirement to undertake a higher degree would be welcomed. Shift systems are
      unpopular and the reduction of 'non-medical' tasks with a reduction in work
      intensity is perceived to be more important than further reductions in hours
      available for work.

PMID- 9762630
TI  - Do general practitioners know when living wills are legal?
AB  - BACKGROUND: There is growing public awareness of living wills or advance
      directives. Patients who wish to make advance directives may approach general
      practitioners (GPs) for advice. However, many GPs are unaware of the correct
      legal status of living wills. METHODS: Questionnaires were sent to 270 GPs in
      London and Winchester, asking seven questions about the current legal status of
      living wills. RESULTS: Of the 214 GPs (79%) who returned questionnaires, only 104
      (49%) were aware that some types of advance directives could carry legal force.
      Many of the GPs who did know that living wills could be legally binding were
      unable correctly to answer further questions on the practicalities of the law;
      for example, 26% were wrong in believing that a lawyer had to draw up a living
      will, and 13% incorrectly believed that a doctor was legally required to give any
      treatment requested by a patient in a living will. CONCLUSIONS: Half of the GPs
      surveyed were unaware that living wills currently have legal force and most of
      the rest were unaware of important details of the law. More attention needs to be
      given to the education of doctors in this area.

PMID- 9762631
TI  - Successful medical treatment of peptic pyloric stenosis: Dr Sippy revisited.
AB  - BACKGROUND: Surgery and balloon dilatation are perceived by many as the principal
      treatments for peptic pyloric stenosis. We questioned whether, with the
      availability of modern acid suppressant treatment, this was still appropriate or
      whether patients could be managed with medical treatment alone. METHODS:
      Seventeen consecutive patients with peptic pyloric stenosis were treated with
      endoscopic gastric drainage, followed by oral omeprazole in 15 or cimetidine in
      two. Gastric emptying half times for solids and liquids were assessed in 11 of
      the 17 patients when they had become asymptomatic. RESULTS: Endoscopic drainage
      and medical treatment successfully relieved symptoms in all 17 patients, although
      the gastric emptying studies in 11 patients still showed prolongation in eight.
      Symptoms resolved completely after a mean of 28 days. Five patients relapsed when
      changed from omeprazole to cimetidine treatment, but all responded to re-starting
      omeprazole. Four patients remain well on cimetidine alone. CONCLUSIONS: Medical
      treatment preceded by endoscopic gastric drainage was effective in all patients
      in this series and may be the preferred choice of treatment in patients with
      pyloric stenosis.

PMID- 9762632
TI  - Prescribing alcohol in a general hospital: 'not everything in black and white
      makes sense'.
AB  - The policies and practicalities of prescribing alcohol for inpatients at a
      teaching hospital were examined. Sources of information easily available to
      hospital medical staff were searched for guidance on the prescription of alcohol.
      No guidance relevant to clinical practice was found. Current practice in a single
      hospital was examined using a semistructured staff interview. While nurses and
      doctors suggested a wide range of indications for prescribing alcohol, most of
      these are not supported by evidence and for some, such as alcoholism and
      depression, alcohol would be contra-indicated. The persistence of alcohol
      prescribing in hospital is based on tradition rather than evidence of its
      effectiveness. It sends an undesirable message to patients who may be suffering
      from alcohol-related medical disorders, and it is time to discontinue this
      outdated clinical practice.

PMID- 9762633
TI  - The enigma of autonomic failure in diabetes.
AB  - The extent of autonomic failure in diabetes and the damage that results both in
      terms of structure and function is seldom realised. This article focuses on the
      consequences of autonomic denervation of several different forms of smooth
      muscle, notably those of arterial wall, vas deferens, stomach, iris and bronchial
      wall. The clinical implications of these changes are described, in particular the
      problems arising from vascular (and vas deferens) calcification and abnormalities
      of vascular reactivity; insulin-induced postural hypotension and the splanchnic
      circulation; the anaemia of autonomic neuropathy from failure of erythropoietin
      production; gastromyopathy as a cause of gastroparesis; iritis as a symptom
      related to diabetic autonomic neuropathy (DAN); the concept of an autoimmune
      basis for DAN; and failure of bronchial reactivity and respiratory arrests in
      DAN. The importance of clinical observation leading to clinical experiment and
      research, together with the stimulation of ideas by collaboration with clinical
      colleagues in other disciplines is emphasised throughout.

PMID- 9762634
TI  - The end of medical history?

PMID- 9762635
TI  - Shared care in HIV and AIDS: shifting care or shifting costs?

PMID- 9762636
TI  - Medical problems in obstetric practice.

PMID- 9762637
TI  - A European exchange scheme.

PMID- 9762638
TI  - Evidence-based medicine.

PMID- 9762639
TI  - The future of general medicine.

PMID- 9762640
TI  - Increased illness experience preceding chronic fatigue syndrome.

PMID- 9762641
TI  - Fail-safe screening programme.

PMID- 9762642
TI  - Emerging infectious diseases': meeting the challenge. Introduction.

PMID- 9762643
TI  - The future of infectious diseases.

PMID- 9762644
TI  - Emerging and resurgent pathogens in New York City.

PMID- 9762645
TI  - The evolution of virulence and emerging diseases.
AB  - Insights into the evolution of virulence may aid efforts to control or even
      prevent emerging diseases. Specifically, dangerous pathogens can be distinguished
      from those that pose relatively little threat by identifying characteristics that
      favor intense exploitation of hosts by pathogens, hence causing high virulence.
      Studies to date have implicated several such characteristics, including
      transmission by vectors, attendants, water, and durable propagules. These
      insights may improve the return on investments in disease control by directing
      effort and resources to the most-dangerous emerging pathogens. The approach also
      should help us to identify those control measures that will guard against the
      future emergence of dangerous pathogens, even those that have not yet been
      identified.

PMID- 9762647
TI  - Overview: surveillance and sentinel systems.

PMID- 9762646
TI  - Social, behavioral, and demographic factors in emerging infections.

PMID- 9762648
TI  - Household-related variables and reported illness in street vendors and their
      children in a South African city.

PMID- 9762649
TI  - Mortality in Hartford, Connecticut: a comparison with the South Bronx, New York.
AB  - Very high mortality rates have been reported in large inner-city areas such as
      the South Bronx and Harlem in New York City, but also may occur in smaller US
      urban areas. Using published death rates for the South Bronx as the standard, the
      standardized mortality ratio was slightly lower than 1.00 for Hartford,
      Connecticut (population 139,739 in 1990), but more than 1.00 for three
      impoverished Hartford census tracts that contained public housing projects.
      Compared with the South Bronx, death rates in Hartford were lower for human
      immunodeficiency virus (HIV), injury-homicide, and alcohol-drugs, but higher for
      hypertension-stroke (in all three tracts) and cancer (in two of the three
      tracts). Variations in patterns of causes of death among impoverished US urban
      areas have implications for planning epidemiologic studies and targeting
      interventions.

PMID- 9762650
TI  - Addiction treatment: promoting a medical approach to substance use.

PMID- 9762652
TI  - Commentary on "Active immunization against poliomyelitis".

PMID- 9762651
TI  - Active immunization against poliomyelitis. April 2, 1953.

PMID- 9762653
TI  - Decreasing cryptosporidiosis among HIV-infected persons in New York City, 1995
      1997.

PMID- 9762654
TI  - Neuropathology in multiple sclerosis: new concepts.
AB  - Multiple sclerosis lesions are characterized by inflammation, demyelination and a
      variable degree of axonal loss. The patterns of inflammation in MS lesions are
      compatible with a T-lymphocyte mediated immune reaction. The formation of
      demyelinated plaques, however, seem to require additional immunological
      mechanisms. In this review evidence is discussed for a pathogenetic role of
      demyelinating antibodies, toxic macrophage products, cytotoxic T-cells as well as
      metabolic disturbances of oligodendrocytes. It is suggested that the pathological
      heterogeneity regarding the patterns and extent of demyelination, remyelination
      and axonal loss may be the outcome of variable dominant immunopathogenetic
      mechanisms in different multiple sclerosis patients.

PMID- 9762655
TI  - Cerebrospinal fluid--physiology, analysis and interpretation of protein patterns
      for diagnosis of neurological diseases.
AB  - The state of the art in routine CSF analysis is reviewed with particular
      reference to multiple sclerosis regarding: (1) The physiology and pathophysiology
      of blood-CSF barrier function and dysfunction with the CSF flow rate as main
      modulator of blood- and brain-derived protein concentrations in CSF; (2) The
      neuroimmunological aspects regarding (a) patterns of disease-related
      immunoglobulin class response (IgG, IgA, IgM) in actual Reiber graphs with
      reference to specific parameters and optional tests, and (b) the oligoclonal,
      polyspecific antibody synthesis in brain; (3) Particular marker proteins in CSF
      and blood for differential diagnosis of neurological diseases; (4) Mathematical
      base for evaluations of CSF data with an example of a multiple sclerosis patient
      for calculation of intrathecal immunoglobulin and antibody synthesis as well as
      Antibody Index.

PMID- 9762656
TI  - Composite cerebrospinal fluid score in relapsing-remitting and secondary
      progressive multiple sclerosis.
AB  - We investigated whether cerebrospinal fluid (CSF) analysis may differentiate
      between relapsing-remitting (RR) and secondary progressive (SP) multiple
      sclerosis (MS). In 17 RR and 16 SP patients we determined: albumine CSF/PB ratio;
      mononuclear cell (MNC) number, CD4+, CD8+, and B1+ subsets, CD4+/CD8+ ratio; IgG,
      IgG index, IgM, IgM index, complement components C3 and C4, and C3 and C4
      indexes; myelin basic protein; neuron-specific enolase (NSE); S100; and lactate.
      For each parameter the statistical distance was calculated. Then, using linear
      discriminant analysis, we computed a discriminant score, including only variables
      with a P value less than or equal to 0.15: albumin CSF/PB ratio, MNC number, IgM,
      IgM index, C3, C4, NSE, S100, and lactate. The discriminant score allocated all
      17 RR patients to the RR group and 15 of 16 SP patients to the SP group. We
      conclude that RR and SP MS patients differ with respect to CSF profile and that
      in individual patients a composite CSF score may differentiate between RR and SP
      MS.

PMID- 9762657
TI  - The intrathecal, polyspecific and oligoclonal immune response in multiple
      sclerosis.
AB  - We report an extended set of neuroimmunological data detected in cerebrospinal
      fluid (CSF) from n = 267 patients with definite multiple sclerosis (MS). Known
      frequencies of oligoclonal IgG (98%), frequencies of intrathecal fractions of
      IgG, IgA and IgM (72%, 9% and 20%, respectively) were confirmed and quantitated
      as intrathecal fractions, IgIF or CSF concentrations, IgLOC. Eighty-nine per cent
      of the patients had a combined 'MRZ-reaction', i.e. intrathecal antibody
      synthesis (Antibody Index, AI > 1.4) against measles, rubella and/or varicella
      zoster virus. Frequencies of single antibodies decreased from measles (78%) to
      rubella (60%), VZV (55%) and HSV (28%). This MRZ-reaction, indicating a chronic
      autoimmune type disease already at time of first clinical symptoms, is less
      sensitive but more specific than detection of oligoclonal IgG. With increasing
      intrathecal IgG synthesis the number of different locally synthesized antibody
      species were increased as well as the amount per species (increased mean AI
      values). The concentration of MRZ antibodies in CSF represents together about 2%
      of intrathecally synthesized total IgG. But, as a very particular result the
      ratio of intrathecally synthesized specific antibody/intrathecally synthesized
      JgG was 5-fold higher (0.24-0.85%) compared to the corresponding ratio in blood
      (0.06-0.17%) of MS patients. This difference between brain ratio and blood ratio
      is discussed to be indicative for the anti-MRZ antibody forming B-lymphocyte
      subset in blood migrating into brain at earlier time of pathophysiological start
      of disease. These results give a concise explanation of neuroimmunological
      aspects in MS, not understood so far.

PMID- 9762658
TI  - CSF-enriched antibodies do not share specificities among MS patients.
AB  - The specificity of the oligoclonal immunoglobulins found in MS CSF is unknown. We
      have previously shown that random peptide libraries displayed on phage can be
      used to identify specific ligands for CSF antibodies. Here we describe the use of
      this tool in the attempt to identify MS-specific CSF-enriched antibody
      reactivities with potential pathogenic, diagnostic or prognostic value. Applying
      different experimental strategies, several ligands reacting with CSF-enriched
      antibodies were identified. When tested against a panel of 55 MS patients, none
      of the ligands found were recognized by antibodies shared by any two patients. We
      used the selected peptides to demonstrate the stability in time of CSF-enriched
      antibodies notwithstanding disease progression.

PMID- 9762659
TI  - Myelin basic protein in CSF as indicator of disease activity in multiple
      sclerosis.
AB  - There is an evident need for a quantitative laboratory marker for ascertaining
      disease activity and treatment effects in multiple sclerosis (MS) patients.
      Activity of the disease process in MS is accompanied by myelin breakdown and
      appearance of myelin basic protein (MBP) in cerebrospinal fluid (CSF). In this
      paper MBP in CSF of relapsing-remitting (RR) MS patients is reviewed. MBP in CSF
      is a fragment containing an epitope corresponding to amino acid residues 45-89 of
      the native molecule. From several relevant studies about CSF MBP in RR MS the
      following relations can be concluded: CSF MBP levels in active MS patients are
      frequently increased (45-100%), remain increased until 5 to 6 weeks after onset
      symptoms and are higher in polysymptomatic exacerbations and correlate with
      number of gadolinium-enhanced (Gd) lesions on MRI, severity of relapses, EDSS
      score and CSF intrathecal IgM synthesis. After an intravenous methylprednisolone
      treatment the increased CSF MBP levels return to normal values and reduction in
      CSF MBP is related to reduction in EDSS score, number of Gd lesions and CSF
      intrathecal IgM synthesis.

PMID- 9762660
TI  - MBP, anti-MBP and anti-PLP antibodies, and intrathecal complement activation in
      multiple sclerosis.
AB  - Intrathecal immunoglobulin synthesis and activation of the complement cascade
      occurs in patients with multiple sclerosis (MS). The present study aimed at
      further studying the relation between intrathecal immunoglobulin synthesis and
      complement activation. We compared total intrathecal synthesis of IgA, IgG, and
      IgM, the number of cells secreting anti-myelin basic protein (MBP) and anti
      proteolipid protein (PLP) antibodies of the IgG isotype and intrathecal
      activation of the complement cascade in patients with possible onset symptoms of
      MS (n = 18) or clinically definite MS (n = 30). Early activation of the
      complement cascade correlated with intrathecal synthesis of IgM. Intrathecal IgG,
      IgA and IgM synthesis also correlated weakly with the presence of cells secreting
      anti-MBP or anti-PLP autoantibodies. Full activation of the complement cascade
      did not correlate with any measures of intrathecal antibody synthesis. These
      findings suggest a complex relation between different immunoglobulin isotypes and
      complement activation which may have similarly complex roles in the pathogenesis
      of MS.

PMID- 9762661
TI  - Can CSF predict the course of optic neuritis?
AB  - To discuss the implications of CSF abnormalities for the course of acute
      monosymptomatic optic neuritis (AMON), various CSF markers were analysed in
      patients being randomly selected from a population-based cohort. Paired serum and
      CSF were obtained within a few weeks from onset of AMON. CSF-restricted
      oligoclonal IgG bands, free kappa and free lambda chain bands were observed in
      17, 15, and nine of 27 examined patients, respectively. Sixteen patients showed a
      polyspecific intrathecal synthesis of oligoclonal IgG antibodies against one or
      more viruses. At 1 year follow-up five patients had developed clinically definite
      multiple sclerosis (CDMS); all had CSF oligoclonal IgG bands and virus-specific
      oligoclonal IgG antibodies at onset. Due to the relative small number studied at
      the short-term follow-up, no firm conclusion of the prognostic value of these
      analyses could be reached. CSF Myelin Basic Protein-like material was increased
      in only two of 29 patients with AMON, but may have potential value in reflecting
      disease activity, as the highest values were obtained among patients with CSF
      sampled soon after the worst visual acuity was reached, and among patients with
      severe visual impairment. In most previous studies of patients with AMON
      qualitative and quantitative analyses of CSF IgG had a predictive value for
      development of CDMS, but the results are conflicting.

PMID- 9762662
TI  - Immune pathogenesis of multiple sclerosis. Brain autoimmune reactivity and its
      control by neuronal function.

PMID- 9762663
TI  - Are there any body fluid markers of brain atrophy in multiple sclerosis?
AB  - The weak correlation between inflammatory activity and disease progression in
      patients with multiple sclerosis has shifted the emphasis from inflammatory
      monitoring to the investigation of the pathological processes of demyelination,
      axonal loss, and gliosis. New magnetic resonance imaging (MRI) techniques that
      have been developed to measure these processes appear very promising. This paper
      will briefly discuss potential body fluid markers of axonal loss, gliosis and
      demyelination, as the pathological substrates of brain atrophy, their function
      and the principles behind their future study in patients with multiple sclerosis.

PMID- 9762664
TI  - Data on cytokine mRNA expression in CSF and peripheral blood mononuclear cells
      from MS patients as detected by PCR.
AB  - Reverse transcription polymerase chain reaction (RT-PCR) was used to amplify the
      mRNA coding for different cytokines in peripheral blood mononuclear cells (PBMC)
      and cerebrospinal fluid (CSF) cells from 18 multiple sclerosis (MS) patients as
      compared with 21 other neurological patients. mRNA levels were quantitated by
      radioactive hybridization of the PCR products. Expression of tumor necrosis
      factor (TNF)-alpha, interferon (IFN)-gamma, and interleukin (IL)-10 mRNA was
      elevated in CSF cells of MS patients. In many MS patients, both proinflammatory
      and immunoregulatory cytokine messages were detected in the CSF compartment. Such
      immune reactivity of CSF cells, as opposed to PBMC, was not associated with
      higher clinical activity of the disease. Expression of the B7.1 accessory
      molecule mRNA was similarly investigated. In the CSF, it was detected only in
      some clinically active MS cases and in other inflammatory diseases.

PMID- 9762665
TI  - Therapy with antibodies against CD40L (CD154) and CD44-variant isoforms reduces
      experimental autoimmune encephalomyelitis induced by a proteolipid protein
      peptide.
AB  - Interactions between mononuclear cells are required for the formation of
      inflammatory infiltrates in the CNS and the activation of cellular effector
      functions provoking demyelination in MS. Membrane-expressed costimulatory
      molecules are crucial to such interactions. We therefore investigated whether two
      costimulatory molecules, CD40L (CD154, expressed on activated CD4-possible T
      cells) and selected CD44-variant isoforms (expressed on activated CD4-positive T
      cells), are targets for immunotherapy in MS. The model of experimental autoimmune
      encephalomyelitis (EAE) induced in SJL-mice by immunization with a peptide
      derived from the proteolipid protein (PLP139-151) was optimized to address these
      questions. A previous observation that anti-CD40L (CD154) monoclonal antibodies
      can effectively prevent EAE in this model was confirmed, and extended by
      demonstrating that CD40 is expressed by cells of the monocytic lineage
      infiltrating the spinal cord. In vivo treatment with antibody against the
      standard isoform of CD44 (CD44s or CD44H) did not affect disease burden. In
      contrast, combined treatment with antibodies against the isoforms CD44v6, v7 and
      v10, which are thought to be involved in inflammatory processes, reduced the
      disease burden considerably. In addition, CD44v10-expressing cells were detected
      in the spinal cord. These data support the idea that CD40-CD40L interactions form
      a target for immunotherapy of MS, and indicate that cells expressing CD44v6, v7
      and/or v10-containing isoforms have such potential as well.

PMID- 9762666
TI  - T cell receptor V beta 5 and V beta 17 clonal diversity in cerebrospinal fluid
      and peripheral blood lymphocytes of multiple sclerosis patients.
AB  - To better characterize the cellular immune response taking place in the MS
      central nervous system, we investigated the blood and CSF T cell receptor (TCR) V
      beta 5 and V beta 17 repertoire in HLA-typed patients with recently diagnosed MS
      or other neurological diseases (OND). Using a RT-PCR based technique, we analysed
      directly ex vivo the CDR3 size of TCR beta chains utilizing V beta 5 (eight
      patients with MS and one with OND) or V beta 17 (eight patients with MS and six
      with OND) gene segments on paired blood-CSF samples. Globally, the analysis of V
      beta 5-J beta and V beta 17-J beta repertoire showed a less diverse pattern in
      the CSF samples than in the corresponding peripheral blood lymphocytes both in MS
      and in OND patients. However, we did not detect any recurrent clonal expansion
      within the V beta 5+ T cells in MS patients, underlining the potential limits of
      V beta 5-based immunotherapy in MS. We found an expanded T cell population using
      the same V beta 17-J beta 1.6 combination with identical CDR3 length in the CSF
      of three MS patients and none of the control patients. These results suggest
      selective expansion of T cells expressing this segment gene in the MS central
      nervous system.

PMID- 9762667
TI  - Monocyte activation in multiple sclerosis.
AB  - Monocytes, macrophages, and microglia have a central role in the CNS inflammation
      of MS. Monocytes are important in the earliest events in MS. Peripheral blood
      monocytes secrete prostaglandins before MS attacks. During clinical activity
      monocyte activation markers increase and IL-1 and TNF-alpha levels are elevated.
      Other monocyte products such as IL-10 reduce inflammation. IL-10 mRNA in MNC is
      increased during stable disease. Manipulation of monokine secretion and
      expression of monocyte surface proteins are reasonable approaches for immune
      therapy of MS.

PMID- 9762668
TI  - Cytokines in multiple sclerosis: pro-inflammation or pro-remyelination?
AB  - The targets of the inflammatory response in multiple sclerosis (MS) are myelin
      and the myelin producing cells, oligodendrocytes. The infiltration of activated
      immune cells and recruitment of endogenous glia lead to the destruction of myelin
      and oligodendrocytes, a process that is compounded by the release of cytokines by
      infiltrating cells. Recent evidence suggests that key cytokines that are
      responsible for the destruction of myelin may also mediate the process of
      remyelination and repair. It appears that both inflammatory and repair processes
      are governed by the temporal and spatial relation of cytokines to their targets.

PMID- 9762669
TI  - Time-course analysis of CD25 and HLA-DR expression on lymphocytes in interferon
      beta 1b-treated multiple sclerosis patients.
AB  - To identify immunological markers that could be used to monitor relapsing
      remitting multiple sclerosis (RRMS) course/activity during interferon beta 1b
      (IFN beta 1b) therapy, we longitudinally studied HLA-DR and CD25 expression by T
      lymphocytes in 15 IFN beta 1b-treated RRMS patients. Peripheral blood T cell
      subsets were analysed before therapy (T0), and after 1 (T1), 2 (T2), 3 (T3), 6
      (T4) and 12 (T5) months after therapy initiation. HLA-DR expression and the
      CD3+HLA-DR+ T cell number showed a peculiar trend in almost all (14/15) the
      patients: a significant decrease at T1 and T2 followed by a return to pre
      treatment levels from T3 to T5. At T1 and T2, eight patients showed an up
      regulation of CD25 on CD4, as well as an increase in the CD4+CD25+ cell number.
      However, a marked, significant reduction of this T cell subset was observed in
      all the patients at T3, followed by the progressive return to pre-treatment
      values from T4 to T5. All the patients developed anti-IFN beta 1b 'binding'
      antibodies within the first three months of therapy. Our findings demonstrate
      that: (1) the expression of HLA-DR and CD25 on T cells, as well as the number of
      circulating CD3+HLA-DR+ and CD4+CD25+ cells, are only transiently reduced in vivo
      in IFN beta 1b-treated RRMS patients, (2) the expression of HLA-DR and CD25 on T
      lymphocytes cannot be used to monitor MS course/activity during IFN beta 1b
      therapy, (3) the long-lasting beneficial effect of IFN beta 1b on RRMS reported
      in the literature cannot be explained by the down-regulation of MHC class II
      antigens and/or interleukin-2 receptor expression induced by this cytokine.

PMID- 9762670
TI  - Correlation of soluble adhesion molecules in blood and cerebrospinal fluid with
      magnetic resonance imaging activity in patients with multiple sclerosis.
AB  - Several studies have reported a positive correlation between levels of soluble
      adhesion molecules in serum or cerebrospinal fluid and cranial MRI activity. We
      performed a cross-sectional study in 46 patients with newly diagnosed MS and
      determined levels of soluble intercellular adhesion molecule-I (sICAM-I) as well
      as vascular cell adhesion molecule-I (sVCAM-I) in correlation to the number and
      area of gadolinium enhancing lesions on cranial magnetic resonance images (MRI).
      The data revealed a significant positive correlation between sVCAM-I serum levels
      and gadolinium enhancing lesions. In addition, CSF to serum ratios for sICAM-I
      and sVCAM-I correlated to MRI activity. In patients with a single enhancing
      lesion (SEL) there was a negative correlation between the QsCAM and the distance
      of the SEL to the ventricles. As these adhesion molecules are stable and markers
      of disease activity in MS, we further investigated sVCAM-I serum levels during
      treatment with interferon beta-Ib (Betaferon). Significant increases in serum
      levels for sVCAM-I in patients receiving Betaferon were associated with a
      favourable treatment response after 1 year in 17 out of 19 patients and
      correlated to decreased MRI activity, whereas stable or reduced sVCAM-I levels
      occurred more often in non-responders (five out of six patients). Therefore it
      can be hypothesized that soluble adhesion molecules are released from cerebral
      endothelial cells as an early immunoregulatory activity of the immune system to
      reduce cellular traffic across the blood brain barrier and this is further
      enhanced by IFN-beta treatment.

PMID- 9762671
TI  - Serum soluble intercellular adhesion molecule-I in MS: relation to clinical and
      Gd-MRI activity and to rIFN beta-Ib treatment.
AB  - The validity of serum sICAM-I levels to assess Multiple Sclerosis (MS) activity
      was evaluated in 49 untreated definite relapsing-remitting (RR) patients. sICAM-I
      levels were significantly (P = 0.0009) higher in the 'clinically active' group
      (No 22) than in the 'clinically inactive' (No 27), whereas no different values
      were found between patients with Gd-enhancing lesions at MRI (Gd-positive) (No
      32) and patients without such lesions (Gd-negative) (No 17) independently of
      their clinical activity. Among the 'clinically active' MS, the Gd-positive (No
      16) subgroup showed significant (P < 0.05) lower sICAM-I levels when compared to
      the Gd-negative (No 6) subgroup, but higher (P = 0.009) than those of the
      'clinically inactive Gd-positive' (No 16) patients. The sICAM-I levels did not
      differ between the two 'clinically inactive' subgroups Gd-positive (No 16) and Gd
      negative (No 11). Finally the clinically active Gd-negative (No 6) showed sICAM-I
      levels higher (P = 0.002) than the clinically inactive Gd-negative (No 11). The
      specificity of high serum sICAM-I levels (above M +/- 2 s.d. of control values)
      to assess the disease activity in MS resulted higher (100%) using clinical than
      Gd-MRI activity (76%) as gold standard. The changes induced by 1 year recombinant
      Interferon-beta-Ib (rIFN beta-Ib) treatment on sICAM-I serum levels were also
      longitudinally investigated in 36 of the 49 RR MS. sICAM-I levels at baseline
      significantly increased in the first 2 months (baseline vs 1st month P < 0.0001
      and 1st vs 2nd month P = 0.02), persisted at high levels without any significant
      change after 3 months, showed a temporary decrease at 6 months, then
      significantly increased again at 9 and 12 months. Fourteen patients experienced
      relapses, with a total of 20 relapses, during the whole treatment duration. The
      mean relapse/rate and the frequency of patients with Gd-positive MRI scans
      resulted significantly higher in the first semester compared to the second
      semester of treatment. This study adds further insights into the validity of
      serum sICAM-I to assess disease activity in MS and on the immunomodulatory
      properties of rIFN beta-Ib.

PMID- 9762672
TI  - Monitoring multiple sclerosis course and activity with TNF-alpha.

PMID- 9762673
TI  - Relapse markers in multiple sclerosis: are in vitro cytokine production changes
      reflected by circulatory T-cell phenotype alterations?
AB  - In vitro tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma)
      and interleukin-2 (IL-2) production, serum neopterin levels, and T-lymphocyte
      subpopulations were determined on a monthly basis in 22 MS patients. We found
      increased in vitro TNF-alpha production from 4 weeks on prior to the day of an
      exacerbation. There was a significant correlation with in vitro IFN-gamma
      release, the absolute blood monocyte count and the serum neopterin levels,
      suggesting that monocytes stimulated by IFN-gamma play an important role in the
      TNF-alpha production. Serial analysis of in vitro TNF-alpha production proved to
      be a helpful tool in predicting relapses in MS patients. Furthermore, elevated
      levels of IFN-gamma and IL-2 after stimulation with OKT3 during exacerbations
      were demonstrated. These increases were not reflected by changes in T-lymphocyte
      subpopulations. However, significant differences in T-cell subsets were observed
      between controls and relapsing progressive patients.

PMID- 9762674
TI  - In vitro cytokine profiles as indicators of relapse activity and clinical course
      in multiple sclerosis.
AB  - In vitro production of tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL
      2), IL-4, IL-6, IL-10 and oligoclonal IgG (IgG OB) was evaluated in the aim to
      investigate their profile in correlation with multiple sclerosis (MS) clinical
      activity and clinical course. Whole blood stimulation with lipopolysaccharide or
      concanavalin A was performed in 61 patients presenting with relapsing-remitting,
      relapsing-progressive or chronic progressive MS; treatments received were: none,
      azathioprine (AZA), cyclosporin, cyclophosphamide, subcutaneous interferon-beta
      1a (IFN-beta 1a) and corticosteroids (CST). The cinetics of cytokine production
      showed that (i) in the absence of treatment, TNF-alpha and IL-6 dropped
      respectively after and during the periods surrounding relapse, while IL-4 was
      increasing before and IL-10 after relapse; (ii) with AZA, TNF-alpha and IL-6
      lowered before exacerbation, IL-4 prolonged high levels after and IL-10 before
      relapse; (iii) with IFN-beta 1a, IL-10 was already increasing before relapse, and
      TNF-alpha was higher after relapse. When cytokine levels were analysed
      independently from MS clinical activity, the use of AZA inhibited IgG OB and TNF
      alpha synthesis (P = 0.002) but increased IL-4 (P = 0.0024), whereas IFN-beta 1a
      stimulated TNF-alpha and inhibited IgG OB and IL-4 production. CST inhibited TNF
      alpha, IL-6, IL-4 and IgG OB synthesis. This study stresses both the weight of
      clinical parameters and of methodology used in results obtained in cytokine
      analysis in MS.

PMID- 9762675
TI  - Myelin reactive T cells in the autoimmune pathogenesis of multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous
      system (CNS) leading to demyelination. Although it is widely accepted that
      demyelination in MS results from an active inflammatory process, the cause of the
      inflammation is still not completely resolved. Findings in experimental
      autoimmune encephalomyelitis (EAE), an animal model of MS, and observations in
      human MS have led to the hypothesis that MS is an autoimmune disease mediated by
      autoreactive T cells with specificity for myelin antigens. The identity of the
      brain antigen(s) which is (are) the primary target(s) of the autoimmune process
      is not known, but current evidence indicates that myelin basic protein (MBP) is a
      likely candidate. In this paper we will overview some of the experimental
      evidence suggesting that MBP reactive T cells hold a central position in the
      pathogenesis of MS, and discuss some of the currently tested therapeutic
      strategies in MS which are directed towards the pathogenic MBP reactive T cells.
      Although there appears to be no direct correlation between anti-MBP T cell
      responses and clinical disease activity, some recent observations suggest that
      monitoring of anti-MBP T cell responses could be helpful to study immunological
      efficacy of experimental immunotherapies in MS.

PMID- 9762676
TI  - The potential role of nitric oxide in multiple sclerosis.
AB  - Nitric oxide (.NO) and its reactive derivative peroxynitrite (ONOO-) have been
      implicated in the pathogenesis of multiple sclerosis (MS). They are cytotoxic to
      oligodendrocytes and neurones in culture by inhibiting the mitochondrial
      respiratory chain (complexes II/III and IV) and inhibiting certain key
      intracellular enzymes. Recently .NO has been implicated as a possible
      aetiological factor in reversible conduction block in demyelinated axons.
      Inducible nitric oxide synthase (iNOS) is upregulated in the central nervous
      system of animals with experimental allergic encephalomyelitis (EAE) and in
      patients with MS. In some EAE models inhibiting iNOS activity decreases disease
      severity whilst in other models disease activity is exacerbated. Raised levels of
      nitrate and nitrite, stable end-products of .NO/ONOO-, are found in the
      cerebrospinal fluid, serum and urine of patients with MS. CSF levels of nitrate
      and nitrite correlate with blood-brain-barrier dysfunction, which suggests that
      .NO may play a role in inflammatory blood-brain-barrier dysfunction. In a
      longitudinal study on 24 patients with relapsing remitting and secondary
      progressive MS, raised serum nitrate and nitrite levels correlated with a
      relapsing course and infrequent relapses. However, no correlation was found
      between raised serum levels of nitrate and nitrite and MRI activity, disease
      progression, or the development of cerebral atrophy. In autoimmune mediated CNS
      demyelinating disease .NO may be a double-edged sword, mediating tissue damage on
      the one hand and on the other hand modulating complex immunological functions
      which may be protective.

PMID- 9762677
TI  - A unique population of circulating autoantibodies promotes central nervous system
      remyelination.
AB  - In previous studies we demonstrated that the humoral immune response directed
      against unique central nervous system (CNS) antigens enhanced CNS remyelination
      in the Theiler's virus experimental model of multiple sclerosis (MS). To expand
      on this observation, a mouse IgM kappa monoclonal antibody (mAb) which enhances
      CNS remyelination, was raised against normal mouse spinal cord homogenate.
      Characterization of this mAb revealed that it is polyreactive towards variety of
      intracellular antigens but also reacts to an unidentified surface antigen on
      oligodendrocytes. The mAb is encoded by germline immunoglobulin genes without
      somatic mutations consistent with the observation that it is a natural
      autoantibody. Recently we generated another mouse IgM kappa mAb raised against
      normal spinal cord homogenate, which also promotes CNS remyelination. Further
      characterization revealed that both mAbs which promote remyelination have similar
      binding characteristics. Conventionally Abs which recognize normal CNS
      components, especially oligodendrocytes or myelin, have been considered to be a
      disease marker or be involved in the pathogenesis of MS. However, we have
      identified a unique population of circulating autoantibodies which are beneficial
      for myelin repair. Therefore this observation indicates the need to reevaluate
      autoantibody production against myelin components in CSF and blood as markers of
      disease activity versus repair in MS.

PMID- 9762678
TI  - A gene therapy approach to treat demyelinating diseases using non-replicative
      herpetic vectors engineered to produce cytokines.
AB  - A successful gene therapy approach in organ-specific autoimmune diseases, such as
      multiple sclerosis (MS), encompasses the inhibition of the autoreactive T cells
      or the modification of the target organ cells by the introduction of exogenous
      'protective' genes. In MS, an autoimmune disease of the central nervous system
      (CNS), the inciting autoantigen is still unknown and therefore the isolation of
      autoreactive T cells may only be inferential. At present, gene therapy approaches
      in MS should therefore aim to the modification of the target organ. Possible
      candidate genes to be transferred within the CNS of MS patients are those coding
      for anti-inflammatory cytokines (i.e. interleukin-4, interleukin-10, transforming
      growth factor beta) which have been shown to ameliorate demyelinating diseases at
      least in experimental models. However, a limiting factor for this therapy is the
      difficulty to reach the CNS. A gene therapy approach using viral vectors able to
      infect post-mitotic cells, such as those present within the CNS, without inducing
      toxic reactions, may overcome this limitation. We propose to use non-replicative
      herpetic vectors, which represent a viable gene-transfer alternative to the
      classical retroviral and adenoviral vectors. Key advantages are their size, able
      to accommodate multiple foreign genes, and their ability to infect post-mitotic
      cells such as those present within the CNS. We first transferred a gene coding
      for interleukin-4 within the CNS of mice undergoing experimental allergic
      encephalomyelitis, an animal model for MS, using non-replicative Herpes Simplex
      Virus type 1-derived vectors. We found that this approach ameliorates the disease
      course and delays the disease onset. The establishment of this technique to
      deliver anti-inflammatory cytokines within the CNS using herpetic vectors should
      clarify the role of individual cytokines in the demyelinating process and allow
      assessment of whether gene therapy using herpetic vectors is a feasible and safe
      approach to treat human demyelinating disorders.

PMID- 9762679
TI  - Are there indicators of remyelination in blood or CSF of multiple sclerosis
      patients?
AB  - Knowing the mechanisms and the times of remyelination is not only an intriguing
      scientific challenge but it has also important consequences on the therapeutic
      approach to multiple sclerosis (MS). The neural-cell adhesion molecule (N-CAM)
      shows tempting suggestions about its possible involvement in reparative
      mechanisms, and, finally, in remyelination. In fact, its levels progressively
      increase in the cerebrospinal fluid (CSF) of acute MS patients, paralleling the
      progressive clinical improvement after the attack. Some information is also given
      about the ciliary neurotrophic factor (CNTF), whose CSF levels were found to be
      increased in MS patients who were recovering from an acute exacerbation.

PMID- 9762680
TI  - Disease activity and the immune set in multiple sclerosis: blood markers for
      immunotherapy.
AB  - There is no established immunological marker of multiple sclerosis activity,
      which reflects the poor understanding of the immunopathogenesis of multiple
      sclerosis. Passive measurement of the levels of soluble inflammatory markers,
      whose half lives are usually measured in minutes and hours, can only indicate the
      extent of instantaneous inflammation, which is known to fluctuate in multiple
      sclerosis. We favour measurement of immune responses in vitro. As healthy
      individuals have T cell reactivities to myelin proteins that are postulated to be
      pathogenic in multiple sclerosis, we prefer non-antigen specific mitogen and
      recall antigen assays as immunological markers. We illustrate their use in the
      treatment of 27 patients with multiple sclerosis using a pulse of humanised anti
      lymphocyte (CD52) antibody that caused prolonged T cell depletion. The mitogen
      induced proliferation, and secretion of IFN-gamma, from peripheral blood
      mononuclear cells in vitro was significantly reduced after treatment, suggesting
      that immune responses had been modulated. Such observations will only gain
      credence as an outcome measure if they are shown to correlate with clinical or
      radiological measures of multiple sclerosis activity. Perhaps more importantly,
      aspects of the pathogenesis of multiple sclerosis may be revealed by close
      immunological surveillance of patients undergoing experimental treatments.

PMID- 9762681
TI  - The expression of integrins on activated T-cells in multiple sclerosis. Effect of
      intravenous methylprednisolone treatment.
AB  - We studied the effect of intravenous methylprednisolone (MP) on the expression of
      the integrins, LFA-1 and VLA-4, on activated blood T-lymphocytes in 17 patients
      with relapses of clinically definite relapsing-remitting MS. MP treatment did not
      induce changes in the expression of CD3, CD4, DR, LFA-1 or VLA-4 markers when
      measured in the total population of lymphocytes in MS patients in relation to
      treatment. Treatment influenced neither the LFA-1 nor VLA-4 positive cells within
      the CD3+ population. MP treatment clearly decreased the DR+ CD3+ cells (P < 0.01)
      and the percentage of DR+ CD3+ lymphocytes bearing VLA-4 (P < 0.01). However,
      this was not the case when we studied the percentage of lymphocytes which
      expressed LFA-1. Glucocorticoids did not influence the mean intensity of the
      expression of the two integrins quantified in either total or DR+ CD3+
      lymphocytes. Although, further research seems warranted to investigate a possible
      effect of MP on lymphocyte integrin function, this work corroborates the idea
      that MP treatment may interfere with the mechanisms of T-cell migration into CNS,
      thus modulating the activity of multiple sclerosis.

PMID- 9762682
TI  - Myelin basic protein-like material in the urine of multiple sclerosis patients:
      relationships to clinical and neuroimaging changes.
AB  - Urinary myelin basic protein-like material (MBPLM) represents material which is
      cross-reactive with a cryptic epitope in peptide 84-89 of human myelin basic
      protein. While normally present at moderate levels in the adult, these levels
      rise higher in patients who have secondary progressive multiple sclerosis (MS).
      The increase in urine MBPLM correlates with the burden of disease detected by T2
      weighted cranial magnetic resonance imaging. There is no correlation between
      urinary MBPLM and acute disease activity in relapsing-remitting MS. The first
      major need for improving the clinical utility of measurements of MBPLM in urine
      in MS patients is to delineate its exact chemical features so that assays may be
      improved and a potential biological role of the MBPLM better understood. The
      second major task is to apply the group data accumulated and apply them to
      individual patients. This could prove to be means to individually direct
      treatment and determine its effectiveness.

PMID- 9762683
TI  - Urinary markers of disease activity in multiple sclerosis.
AB  - Numerous markers of disease activity, representing different aspects of the
      inflammatory cascade and pathogenic process in multiple sclerosis, can be
      detected in the urine. Urinary monitoring provides distinct advantages over blood
      and cerebrospinal fluid: it is easier to collect, allows frequent sampling and
      acts as a natural integrator by capturing the excretion of a substance over a
      prolonged period of time. We will discuss the principles, advantages, and
      pitfalls of urinary monitoring in relationship to multiple sclerosis.

PMID- 9762684
TI  - Free light chains in multiple sclerosis urine.
AB  - We measured free kappa (kappa) and lambda (lambda) light chains in urine from
      patients with definite multiple sclerosis (MS), other neurologic diseases (OND),
      and normal controls by using an enzyme linked immunosorbent assay. Both kappa and
      lambda light chains were higher in MS than OND or controls. In seven of eight
      relapsing-remitting (R-R) MS patients serial studies showed that urinary kappa
      chains were elevated during periods of worsening, and decreased during clinical
      recovery. In contrast, the levels of kappa chains did not correlate with clinical
      activity in 10 progressive (P) MS patients. Further correlation of urinary light
      chains with neurologic evaluations in R-R and P MS patients over a longer period
      are needed to determine their clinical and biological relevance.

PMID- 9762685
TI  - Identification of brain atrophy with MRI in MS.

PMID- 9762686
TI  - Neurophysiological and cognitive markers of disease evolution in multiple
      sclerosis.
AB  - Both evoked potentials and cognitive tests may provide useful information which
      cannot be derived from the clinical observation. For this reason, there have been
      some attempts to use EPs in monitoring the natural history of the disease and in
      assessing the efficacy of therapeutic trials. However, no conclusion can be
      derived from the few available data. Although MRI is more sensitive than EPs in
      revealing new lesions in brain, cerebellum and brainstem, EPs are more sensitive
      in revealing optic nerve and spinal cord lesions. Moreover, the poor relationship
      between brain MRI abnormalities and disability has raised the possibility that
      cognitive evaluation may be an additional sensitive marker of brain involvement
      over time. Since the gold standard for the assessment of disease activity is
      uncertain, it is therefore advisable that frequent MRI, EPs and cognitive
      assessment may integrate clinical outcomes measured by conventional scales, both
      in the study of the natural disease course and in monitoring clinical trials.

PMID- 9762687
TI  - Body fluid markers to monitor multiple sclerosis: the assays and the challenges.
AB  - The need for reliable markers of disease activity in multiple sclerosis (MS) to
      better guide basic research, diagnosis, treatment, and monitoring of therapy is
      well-recognized. A recent European Charcot Foundation Symposium (Body fluid
      markers for course and activity of disease in multiple sclerosis (Madrid, Spain,
      October 2-4, 1997) organized by the European Charcot Foundation and the Fundacion
      Espanola de Esclerosis Multiple (the Spanish Multiple Sclerosis Foundation)
      brought together experts in the field to review the state of the art for the
      technology measuring markers in body fluids. An array of different approaches was
      presented to measure a wide diversity of classic and novel marker molecules,
      including cytokines, adhesion molecules, myelin compounds, and free antibody
      light chains, in either blood, urine, or cerebrospinal fluid. Here, recent
      progress in these approaches is assessed in the context of distinct
      pathophysiological stages of the disease, the requirements which such molecules
      and assays should ideally meet, and the practical and conceptual challenges which
      they face. Recommendations for further improvements are described.

PMID- 9762688
TI  - Intracellular bacteria in protozoa.
AB  - Intracellular bacteria in humans are typically detrimental, and such infections
      are regarded by the patients as accidental and abnormal. In protozoa it seems
      obvious that many bacteria have coevolved with their hosts and are well adapted
      to the intracellular way of life. Manifold interactions between hosts and
      intracellular bacteria are found, and examples of antibacterial resistance of
      unknown mechanisms are observed. The wide diversity of intracellular bacteria in
      protozoa has become particularly obvious since they have begun to be classified
      by molecular techniques. Some of the bacteria are closely related to pathogens;
      others are responsible for the production of toxins.

PMID- 9762689
TI  - Neuronal control of mammalian vocalization, with special reference to the
      squirrel monkey.
AB  - Squirrel monkey vocalization can be considered as a suitable model for the study
      in humans of the neurobiological basis of nonverbal emotional vocal utterances,
      such as laughing, crying, and groaning. Evaluation of electrical and chemical
      brain stimulation data, lesioning studies, single-neurone recordings, and
      neuroanatomical tracing work leads to the following conclusions: The
      periaqueductal gray and laterally bordering tegmentum of the midbrain represent a
      crucial area for the production of vocalization. This area collects the various
      vocalization-triggering stimuli, such as auditory, visual, and somatosensory
      input from diverse sensory-processing structures, motivation-controlling input
      from some limbic structures, and volitional impulses from the anterior cingulate
      cortex. Destruction of this area causes mutism. It is still under dispute whether
      the periaqueductal region harbors the vocal pattern generator or merely couples
      vocalization-triggering information to motor-coordinating structures further
      downward in the brainstem. The periaqueductal region is connected with the
      phonatory motoneuron pools indirectly via one or several interneurons. The
      nucleus retroambiguus represents a crucial relay station for the laryngeal and
      expiratory component of vocalization. The articulatory component reaches the
      orofacial motoneuron pools via the parvocellular reticular formation. Essential
      proprioceptive feedback from the larynx and lungs enter the vocal-controlling
      network via the solitary tract nucleus.

PMID- 9762690
TI  - Analysis of laughter and speech sounds in Italian and German students.

PMID- 9762691
TI  - Orientation-reversal and phase-reversal visual evoked potentials in full-term
      infants with brain lesions: a longitudinal study.
AB  - The onset and maturation of visual cortical mechanisms can be recorded by using
      steady-state visual evoked potentials. The aim of this study was to evaluate and
      compare orientation-reversal (OR) and phase-reversal (PH) VEP as indicators of
      the maturation of cortical function in a population of fullterm infants with
      brain lesions on neonatal MRI. Forty-six infants with brain lesions on neonatal
      MRI were tested on both PH and OR VEP at 8 reversals/second at the age of 5
      months and, if the responses were not significant, at a lower temporal frequency
      (4 reversals/second). Children whose VEPs were not significant at 5 months were
      tested longitudinally at 6, 9, 12 and 18 months. The results showed that 23 of
      the 46 infants (50%) did not show significant responses at 5 months and that
      while in 7 of the 23 (14% of the whole cohort) the responses became significant
      between 5 and 12 months, in the other 16 infants (34%) the VEP responses were
      persistently abnormal. Children with focal lesions, such as focal infarction or
      haemorrhages, tended to show normal or only mildly delayed VEP while more
      generalised lesions, such as the ones seen in infants with hypoxic-ischaemic
      encephalopathy grade 2 and 3, tended to be associated with abnormal VEP
      responses. The involvement of the optic radiations and occipital cortex was not
      always associated with abnormal VEP responses but the concomitant involvement of
      the basal ganglia was always associated with abnormal VEP. We were also able to
      demonstrate that VEP can be also used as a prognostic indicator: while normal OR
      VEP are reliably associated with a normal visual and neurodevelopmental outcome,
      abnormal 4 OR or 8 PH at 5 months are consistently associated with abnormal
      outcome.

PMID- 9762692
TI  - Characterization of the mitochondrial genome in childhood multiple sclerosis. I.
      Optic neuritis and LHON mutations.
AB  - The occurrence of optic neuropathy in patients with MS-like disorders who carry
      one of the pathogenetically significant LHON mutations as well as the higher
      incidence of maternal transmission in familial cases of MS support the hypothesis
      that mitochondrial genes may be implicated in susceptibility to MS. We sequenced
      the entire mtDNA of six children with MS who developed optic neuritis as early
      and prominent visual involvement. The analysis revealed a high degree of
      nucleotide variations relative to the standard mtDNA sequence. After excluding
      various synonymous nucleotide changes and common neutral polymorphisms, eight
      discrete novel missense mutations within the protein coding, tRNA or rRNA genes
      were detected. None of the eight polymorphic sites were found in common between
      the patients with MS. Of particular interest was the observation that five of six
      children carried a total of nine secondary LHON mutations at nucleotide positions
      4216, 4917 or 13708. We conclude that variation in mtDNA is unlikely to
      contribute to genetic predisposition for MS. However, secondary LHON mutations
      may be regarded as additional risk factor for developing prominent optic nerve
      involvement. The association of individual sets of mtDNA variations with
      phenotypic presentation in certain subgroups of MS patients remains to be
      clarified.

PMID- 9762693
TI  - Correlation between neonatal cranial ultrasound, MRI in infancy and
      neurodevelopmental outcome in infants with a large intraventricular haemorrhage
      with or without unilateral parenchymal involvement.
AB  - During a 7-year-period, 1625 infants of 34 weeks gestation or less were enrolled
      in a prospective ultrasound (US) study. One hundred and eleven (6.8%) infants
      developed a large intraventricular haemorrhage (IVH) with or without unilateral
      parenchymal involvement (PI). Fifty-six of these 111 infants survived (50.4%) and
      in 23 (41%) of them a magnetic resonance imaging (MRI) study was performed beyond
      12 months corrected age. There appeared to be a good agreement between neonatal
      ultrasound findings and MRI changes noted in infancy. Of the 10 cases with a
      large IVH without PI (group A), seven had a VP shunt with complete decompression
      of previously enlarged ventricles. Six of these seven infants had periventricular
      hyperintensity (PVHI) but none developed cerebral palsy (CP). Two of the ten
      cases without a VP shunt had irregular ventricular enlargement (VE) with PVHI in
      one. Both developed CP. Seven cases showed thinning of the corpus callosum. Of
      the 13 cases with a large IVH associated with PI (group B), the site of the PI
      could still be recognised on MRI and the degree of communication of the
      porencephalic cyst (PC) with the lateral ventricles correlated well with neonatal
      US findings. On MRI, VE was present in only 6 cases. Wallerian degeneration was
      present in 9/13 infants and all but one developed a hemiplegia. In 12/13 cases
      there was thinning of the corpus callosum, either focal or diffuse. PVHI was
      present in all infants. In 6/13 PVHI was only present around the PC.
      Neurodevelopmental outcome differed for both groups. CP was only present in 2/10
      infants in group A, compared to 11/ 13 in group B. Global delay, in the absence
      of CP, was more common in infants with a large IVH than in those with associated
      PI. CONCLUSION: Combining neonatal US with MRI in infancy enhances our
      understanding of the long-term effects of severe haemorrhagic brain lesions,
      occurring in preterm infants.

PMID- 9762694
TI  - Clinical observations in autosomal recessive spastic paraplegia in childhood and
      further evidence for genetic heterogeneity.
AB  - Among our 23 families (32 cases) with autosomal recessive hereditary spastic
      paraplegia (AR-HSP) all presenting in childhood, 9 families had the "pure" form.
      Occasional patients with this form had upper extremity hyperreflexia, pes cavus
      and sphincter disturbances, even at the early stages. Fourteen families were
      classified as the "complicated" types which manifested with mental retardation
      and cerebellar abnormalities. The evolution and severity was variable, but was
      generally consistent within families. Carriers (parents) did not manifest any
      signs. A total of 5 multiplex families with "complicated" type were used to test
      for a genetic heterogeneity to the region on chromosome 8p12-q13 where the "pure"
      AR-HSP has been mapped previously. No evidence in favor of linkage was detected
      in 3 of our families, thus we further supported genetic heterogeneity for AR-HSP.

PMID- 9762695
TI  - Altered antioxidant enzyme activities in children with a serious adverse
      experience related to valproic acid therapy.
AB  - Specific oxidative metabolites of valproic acid (VPA) have been associated with
      the clinically defined toxicity of the drug. To investigate the role of enzymatic
      detoxification in clinical toxicity, we compared activities of five antioxidant
      enzymes in 15 patients with a serious adverse experience (SAE) related to VPA
      therapy, to enzyme activities measured in 35 patients with good clinical
      tolerance of VPA, and 50 healthy, age-matched subjects. These enzymes included
      glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), glutathione
      transferase, superoxide dismutase, and catalase in erythrocytes; and GSH-Px in
      plasma. We also determined levels of Se, Cu, and Zn, trace elemental cofactors
      for these enzymes, in plasma from each individual. In patients with a VPA
      associated SAE, GSH-Px was significantly depressed and GSSG-R was significantly
      elevated relative to values for the other groups. Selenium and zinc
      concentrations were lower in SAE patients than in controls. These findings may
      indicate a role for selenium dependent antioxidant activity in individual
      susceptibility to an SAE related to VPA therapy.

PMID- 9762696
TI  - Early and late onset manifestations of cerebral vasculitis related to varicella
      zoster.
AB  - Varicella-zoster associated cerebral vasculitis (VZCV) as a cause of cerebral
      infarction has hitherto been considered a rare condition. Ischemic stroke in
      previously healthy children has occurred during recovery from chickenpox or has
      been attributed to virus reactivation among immunosuppressed patients. The
      clinical, radiologic and immunologic findings in four children with VZCV will be
      reported. Clinical manifestations included sudden onset of hemiparesis, motor
      aphasia and disturbed consciousness in previously healthy children. Only one
      child had a history of chickenpox six weeks prior to the onset of stroke, whereas
      a latency period of up to four years between chickenpox and the onset of stroke
      was found in the other three children. Diagnosis of VZCV was confirmed repeatedly
      by demonstrating intrathecal production of varicella-zoster IgG antibodies in
      three children or a four-fold increase of varicella-zoster serum IgA-antibodies
      in one child. Intrathecal production of antibodies against other latent viruses
      and borreliosis could be excluded. PCR for varicella on CSF, performed in two
      patients, remained negative. No intrathecal production of varicella-zoster
      antibodies has been found in a control group of twenty clinically healthy
      children (age range from 2-18 years) with a previous varicella infection. During
      follow-up two children recovered completely whereas two children still suffer
      from serious neurological deficits. Immunological investigations, performed in
      three children, showed circulating immune-complexes with slightly lowered
      complement concentrations in two patients. In addition a lowered T-helper/T
      suppressor cell ratio of unknown origin was found in three children. These
      immunological findings will be discussed in the light of the pathophysiology of
      VZCV.

PMID- 9762697
TI  - Quantification of cyclical fluctuations in cerebral blood volume in healthy
      infants.
AB  - Cyclical fluctuations in cerebral blood flow velocity in Doppler measurements are
      a well known phenomenon. In 1992 Livera et al have shown in one patient, that
      cyclical fluctuations of cerebral blood volume could be measured with near
      infrared spectroscopy (NIRS). The aim of the present study was a quantification
      of the amplitude of cyclical fluctuations of cerebral blood volume (represented
      by total haemoglobin [Hbtot]) in a large number of healthy infants. Furthermore
      changes of oxygenated haemoglobin (HbO2) and deoxygenated haemoglobin (Hb) were
      investigated. Measurements were done during two hours of undisturbed daytime
      sleep. Fifty-eight infants (30 male, 28 female) were included in the study. All
      but one infant showed cyclical fluctuations. For quantification of cyclical
      fluctuations only periods during quiet sleep with excellent tracing quality were
      used. A number of 7894 cycles was analyzed for each of the three NIRS parameters.
      The median amplitude of the cycling fluctuations was: delta Hbtot 1.1 mumol/l,
      delta HbO2 1.1 mumol/l, and delta Hb 0.2 mumol/l. The frequency was changing
      within a range of 3 to 6 cycles/minute. Polynominal regression analysis showed
      that the relationship of delta HbO2 and delta Hbtot was distinctively stronger
      compared to the relationship of delta Hb and delta Hbtot. In conclusion we think
      that these data represent "normal ranges" for parameter fluctuations in long-time
      NIRS tracings.

PMID- 9762698
TI  - A craniospinal enterogenous cyst: case report.
AB  - An enterogenous cyst of the craniospinal region producing medullary compression
      is reported in a 4.5-year-old boy. The patient presented with stiffness of the
      neck and headache, but otherwise without neurological deficits. Magnetic
      resonance imaging (MRI) demonstrated a high-intensity mass extending from the
      cerebellomedullary cisterna to the second cervical vertebra flattening the
      medulla and the upper cervical cord. Complete recovery ensued following total
      excision of the cyst. Histologically, the cyst was lined by a single layer of PAS
      positive columnar epithelium. Presentation of this unusual case is discussed
      together with a review of the literature.

PMID- 9762699
TI  - Aplasia of the depressor anguli oris muscle: a rare cause of congenital lower lip
      palsy?
AB  - Congenital unilateral lower lip palsy (CULLP) with or without additional
      malformations is a well-known limited variation of congenital unilateral facial
      palsy. Some electromyographical studies referred to a hypoplasia or an aplasia of
      the depressor anguli oris muscle. However, no attempt has been made to
      investigate the cause for this mimical disorder by using imaging procedures. We
      examined the occurrence of the depressor anguli oris muscle in 7 patients
      presenting with congenital lower lip palsy by using B-scan sonography. In 6 of
      the patients, the muscle was well-developed on the affected side, but only in one
      patient the muscle seemed to be completely absent. Thus, in the majority of
      cases, hypoplasia or aplasia of the depressor anguli oris muscle is obviously not
      the reason for this mimical disorder. This observation may be important with
      regard to a possible therapeutic management.

PMID- 9762700
TI  - Familial congenital horizontal gaze paralysis and kyphoscoliosis.
AB  - Congenital horizontal gaze paralysis is a rare disorder which may be associated
      with severe scoliosis of early onset. We present the clinical findings of two
      sisters with this syndrome. The additional finding of a unique pericentric
      inversion of chromosome 12 is considered to be incidental. Every child with
      congenital horizontal gaze paralysis should be evaluated for a possibly
      associated scoliosis. If present, a diagnosis of this presumably autosomal
      recessive syndrome can be made with appropriate treatment and genetic counseling.

PMID- 9762702
TI  - Age-related changes in the cytoarchitectonics of the human sensorimotor cortex.
AB  - The projection zones of the movement analyzer show a level of maturity which is
      required for maintaining the self-regulatory processes in children from the first
      days of life [4, 8]. The cytoarchitectonics of the motor zone of the cerebral
      cortex have been studied in a small number of people and at limited ages [1, 2,
      4, 10]. One of the leading age-related changes consists of changes in neuronal
      and interneuronal connections, which have significant influences on the systems
      organization of the brain and its function as an integral organ. Pyramidal
      neurons are regarded as the main universal type of cortical neuron, in which the
      structure of the receptive surface supports transmission of a wide range of
      polymodal signals [1]. Large pyramidal neurons in layers III and IV can establish
      connections with all the neurons in a column of cells, which apparently leads to
      complete and reliable functional interactions between neurons [1, 6]. The aim of
      the present work was to study the quantitative changes in pyramidal neurons in
      layers III and IV in various fields of the human sensorimotor cortex from birth
      to the age of 20 years.

PMID- 9762701
TI  - Changes in neurotransmitters in multiple sclerosis.
AB  - Patients with multiple sclerosis were found to have increased cerebrospinal
      fluid, noradrenaline, and excitatory amino acid (glutamate and aspartate) levels,
      with increased blood glutamine, asparagine, and glycine levels. An association
      was found between these biochemical parameters and the nature and severity of
      neurological symptoms, as well as with the course of the disease.
      Neurotransmitters are proposed to have a role in the pathogenesis of multiple
      sclerosis, particularly in the biochemical mechanisms of the relationship between
      the nervous and immune systems, as well as in the neurochemical mechanisms
      underlying the development of neurological deficit.

PMID- 9762703
TI  - Differentiation of neurons in the locus ceruleus after allotransplantation into
      previously denervated white rat hippocampus.

PMID- 9762704
TI  - Age-related changes in oxytocinergic neurosecretory cells in the accessory
      magnocellular neuroendocrine nuclei of the hypothalamus in rats.

PMID- 9762706
TI  - Adaptive regulation of the nonlinear dynamics of electrical activity of the
      brain.
AB  - A programmable system was used to provide contingent reinforcement of EEG cycles
      corresponding to a selected criterion in a dynamic regime. Use of automated
      reinforcing stimulation of emotionally positive zones of the hypothalamus led to
      a significant increase in the number of cycles with the characteristics specified
      by the dynamic regime within the dominant EEG frequency bands. This effect lasted
      for some time after withdrawal of reinforcing stimulation, and then died down
      gradually. These changes in the EEG activity structure did not occur in
      conditions of nonassociated hypothalamic stimulation. Pseudoreinforced background
      EEG cycles showed complex nonlinear dynamics with competitive interactions
      between processes in which the large dimensionality of the attractor was
      difficult to interpret because of indeterminacy in the trends of the dominant
      process. In contingent hypothalamic stimulation, the form of the correlation
      integral changed towards a predominance of a single nonlinear process determining
      all the activity recorded. In fact, a single dominant nonlinear process was
      formed, which became responsible for the entire dynamics of the system with
      concordance of its internal structure.

PMID- 9762705
TI  - Ribonuclease improves the state of hippocampal sections in the post-ischemic
      period.
AB  - Living hippocampal slices from Wistar rats were used to study the dynamics of
      changes in population electrical responses in field CA1 to electrical stimulation
      of Shaffer collaterals during the development of ischemia (imposed by exclusion
      of oxygen and glucose from the perfusion solution). These studies showed that
      during ischemia, addition of ribonuclease (a blocker of protein synthesis) to the
      perfusion solution resulted in a significantly smaller increase in the latent
      period of the response and slowed the onset of the reduction in the amplitude of
      the evoked potential, and promoted faster recovery of the response after the
      ischemia session ended. It is suggested that the reduction in protein synthesis
      due to ribonuclease preserved energy reserves in the nerve tissue, which in turn
      promoted more complete recovery of neuron function in the post-ischemic period.

PMID- 9762707
TI  - Role of enkephalinergic brain structures in regulating motivated behavior in rats
      with lesioned serotoninergic neurons.
AB  - The behavioral effects of injections of enkephalin into the substantia nigra or
      dorsal raphe nucleus were studied in rats with lesioned serotoninergic
      structures. Lesions were produced by intracerebral administration of the
      neurotoxin 5,7-dihydroxytryptamine. Treated rats showed normalization of
      conditioned drinking reflex extinction. It is proposed that there is a tight
      connection between the normalizing effects of enkephalin on rat behavior in
      conditions of deficient brain serotoninergic system function and increases in the
      efficiency of presynaptic inhibition of dopaminergic neurons.

PMID- 9762708
TI  - Conditioned reflex release of dopamine in the nucleus accumbens after disruption
      of the hippocampal formation in rats.
AB  - Vital intracerebral microdialysis combined with HPLC with electrochemical
      detection was used to study changes in dopamine release in the nucleus accumbens
      during the development and realization of an emotional conditioned response in
      hooded rats with lesions to the hippocampal formation. These studies showed that
      one month after bilateral administration of ibotenic acid into the hippocampal
      formation, rats had weakened emotional responses to contextual stimuli. The
      process of development of the conditioned reflex was accompanied by higher-level
      and longer-lasting release of dopamine in the nucleus accumbens than in sham
      operated rats. Dopamine release levels in the nucleus accumbens during
      realization of the conditioned reflex to contextual stimuli in rats with
      hippocampal lesions and sham-operated rats were identical.

PMID- 9762709
TI  - Role of the cholinergic systems of the dorsal and ventral striatum of the rat
      brain in controlling learned movements.
AB  - Comparative studies were performed of the effects of injections of a cholinergic
      agonist (carbachol) and antagonist (scopolamine) into the ventral and dorsal
      striatum on the performance of a learned movement involving prolonged maintenance
      of extension of the forelimb in rats. Doses of carbachol (0.03-3.00 micrograms)
      into the ventral striatum were accompanied by increases in the numbers of
      movements with prolonged maintenance of extension with application of pressure
      against an obstacle, with a simultaneous decrease in the percentage of rapid
      nonreinforced movements (by an average of 18.8%). Injections into the dorsal
      striatum disrupted slow movements which were not reinforced during training, on a
      background of stable performance of the learned reflex. Doses of scopolamine (0.3
      3.0 micrograms) into both the dorsal and ventral parts of the striatum produced
      increases (by 22.7 +/- 8.2% and 68.9 +/- 14.3%) in the numbers of rapid
      nonreinforced movements typical of the repertoire of untrained animals. These
      data led to the suggestion that the cholinergic system of the ventral striatum is
      involved in the maintenance of forelimb muscle tone in rats during the
      performance of movements in which pressure is applied to an obstacle. The
      cholinergic system of the dorsal striatum does not have this property, but plays
      a significant role in the process of learning new sensory-controlled movements.

PMID- 9762710
TI  - Adenylate cyclase system of the rat striatum: regulatory properties and the
      effects of gangliosides.
AB  - The activity and regulatory properties of the adenylate cyclase system of the rat
      striatum were studied. Agents such as Gpp(NH)p, forskolin, and NaF were found to
      show classical in vitro stimulation of adenylate cyclase activity in the striatum
      membrane fraction. Dosage of rats with a preparation containing gangliosides (30
      mg/kg, 6 i.p. injections) led to prolonged reductions in basal striatal adenylate
      cyclase activity. Two weeks after ganglioside administration, enzyme activity was
      reduced by 48% and remained lower than in controls (by 18%) even a month after
      injections. In vitro studies of the effects of gangliosides on adenylate cyclase
      activity in whole brain and striatal synaptosomes from rats showed that
      gangliosides have modulating actions on the adenylate cyclase system of the
      striatum, mainly due to changes in the catalytic function of the enzyme itself,
      and have no significant effect on the GTP-binding center of G-protein.

PMID- 9762711
TI  - Morphofunctional studies of the interactions of the glutamatergic, cholinergic,
      and dopaminergic systems in the neostriatum.
AB  - Morphological, electrophysiological, and behavioral experiments were used to
      study the interactions of the glutamatergic, cholinergic, and dopaminergic
      systems in the neostriatum of white rats with unilateral lesions of the
      mesostriatal dopaminergic system induced by 6-hydroxydopamine. The neostriatum
      was shown to contain both synaptic and interneuronal nonsynaptic interactions
      between these neurochemical systems. It is suggested that glutamate, which is
      present in excess in conditions of prolonged dopamine deficiency, has toxic
      effects on corticoneostriatal synaptic connections.

PMID- 9762712
TI  - Possible mechanisms of delay in initiation of voluntary movements.
AB  - Studies were made of psychomotor responses and accompanying cortical evoked
      potentials in healthy subjects and patients with Parkinson's disease.
      Measurements showed that delays in a variety of psychomotor responses resulted
      from delays in movement initiation. The frontal regions showed increases in the
      N2 component of evoked potentials and delayed development of P3 waves. It is
      suggested that delayed initiation of movements in patients with Parkinson's
      disease might be associated with strengthening of frontal inhibitory systems,
      preventing the onset of movements.

PMID- 9762713
TI  - Effects of electrical stimulation of the caudate nucleus on functionally
      identified neurons of the sensorimotor cortex in the cat brain.
AB  - Paired stimulation was used to study the effects of the caudate nucleus on the
      specific and nonspecific responses of projection neurons of the sensorimotor
      cortex in the cat brain. Caudal influences on the neurons being studied had
      insignificant effects on specific peripheral evoked responses. Nonspecific
      peripherally evoked activity was in most cases inhibited by caudate spike
      activity, and the pattern of evoked activity underwent significant modulation in
      conditions of a constant type of peripherally evoked response. It is suggested
      that the caudate nucleus acts as a filter of proprioceptive information in the
      cortex or in pathways to the cortex: specific corticopetal information is passed
      unchanged, while nonspecific signals are predominantly inhibited or significantly
      modulated.

PMID- 9762714
TI  - Activation of the cholinergic system of the striatum improves the differentiation
      of sound signals by dogs.

PMID- 9762715
TI  - Effects of lesions to the parafascicular nuclei of the thalamus on the
      development of a conditioned active escape reflex in rats.

PMID- 9762716
TI  - Effects of lesioning of the parafascicular nucleus of the thalamus on an operant
      food-procuring reflex in rats.

PMID- 9762717
TI  - Spatial organization of afferent inputs to the limbic cortex in rats and cats.

PMID- 9762718
TI  - Residual lesions of operant behavior in monkeys following recovery from MPTP
      induced Parkinson-like syndrome.

PMID- 9762719
TI  - Role of atrial natriuretic peptide in the development of arterial hypertension in
      patients with pubertal hypothalamic syndrome.
AB  - The role of a depressor factor, atrial natriuretic peptide, in the development of
      arterial hypertension in adolescents with pubertal hypothalamic syndrome was
      studied in 52 patients and 13 healthy males aged 13-24 years. The duration of
      disease was 2-11 years. Radioimmunological methods were used to measure plasma
      atrial natriuretic peptide, plasma renin activity, and serum aldosterone.
      Patients with borderline arterial hypertension were found to have a significant
      reduction in their atrial natriuretic peptide levels, and this correlated
      directly with the renin-aldosterone system, demonstrating insufficiency of the
      depressor system in patients with pubertal hypothalamic syndrome and the
      involvement of atrial natriuretic peptide in the development of arterial
      hypertension, along with disturbances in the functional relationship between
      atrial natriuretic peptide and the renin-aldosterone system.

PMID- 9762720
TI  - Desensitization of the post-synaptic membrane of neuromuscular synapses induced
      by spontaneous quantum secretion of mediator.
AB  - Experiments on isolated frog neuromuscular junctions in voltage-clamped
      conditions demonstrated increases in the probability of spontaneous release of
      quanta of mediator, resulting in increases in the K+ ion concentration in the
      perfusion solution, and changes in the endplate miniature current amplitude
      induced by increased quantum generation were studied. Factors promoting the
      desensitization of the post-synaptic cholinergic membrane (inhibition of
      acetylcholinesterase and addition of proadifen) to levels greater than a certain
      (critical) frequency of endplate miniature current of the order of 50 spikes/sec
      were found to result in accumulation of activity and progressive reductions in
      the sensitivity of the post-synaptic membrane to the mediator acetylcholine.

PMID- 9762721
TI  - Effects of delta-sleep-inducing peptide in cerebral ischemia in rats.
AB  - Experimental studies were carried out to investigate the neuroprotective effects
      of delta sleep-inducing peptide in animals with cerebral ischemia induced by
      bilateral compression of both carotid arteries, and to compare the efficacy of
      this peptide with that of MK-801. These studies led to the conclusion that the
      peptide had pronounced anti-ischemic effects, which were evident within 24 h and
      consisted of reductions in the severity of postural abnormalities in rats with
      bilateral cerebral ischemia, along with a reduction in lethality. Comparison of
      the efficacies of peptide and MK-801 showed the peptide to have the greater
      neuroprotective effect. These results are regarded as providing an experimental
      basis for using the peptide as a therapeutic agent in patients with stroke.

PMID- 9762722
TI  - Question of time in studies of the neuronal correlates of behavior.

PMID- 9762723
TI  - Role of the functional state of the central nervous system in the mechanism
      forming responses from the peripheral and central parts of the visual analyzer.
AB  - Chronic experiments on rabbits showed that changes in the functional state of the
      central nervous system induced by Nembutal and changes in the brainstem reticular
      formation induced by aminazine had significant effects on the formation of the
      early receptor potential, a-wave, and oscillatory potentials of retinal ERG
      signals, as well as on oscillatory potentials in the superior colliculi and
      visual cortex. Nembutal inhibited the formation of the early receptor potential,
      the a-wave, and the second and third ERG oscillatory potentials, and had similar
      effects on the oscillatory potentials of the superior colliculi and the visual
      cortex. Only the first oscillatory potential was enhanced in all visual system
      structures. Aminazine had long-lasting enhancing effects on the formation of the
      early receptor potential and the a-wave and on the oscillatory potentials of the
      retina, superior colliculi, and visual cortex. This enhancement may be associated
      with "release" of the retina and central structures from the constant inhibitory
      influences of the brainstem reticular formation.

PMID- 9762724
TI  - Blood flow dynamics in different layers of the somatosensory region of the
      cerebral cortex on the rat during mechanical stimulation of the vibrissae.
AB  - The present work reports studies of the quantitative spatial and temporal
      characteristics of changes in local blood flow in different layers of the
      somatosensory cortex of rats during adequate mechanical stimulation of the
      vibrissae. Studies were performed using 34 Wistar rats. Skull trepanning was
      performed under urethane (1 g/kg) anesthesia. Television-guided microscopy was
      used to introduce a set of three platinum electrodes (100 microns in diameter,
      with tip diameters of 30-40 microns) into the somatosensory cortex projection
      zone of the vibrissae. The first and third electrodes were positioned in cortical
      layers I-III and IV-VI and the central electrode was used to generate hydrogen
      within the tissue. Electrode positions were confirmed histologically after
      experiments. Animals were placed on artificial ventilation and one or all
      vibrissae were stimulated at a frequency of 3 Hz for 60 sec, with interstimulus
      intervals of 3 min. Changes in the local blood flow were measured during
      stimulation and for 1 min afterwards, using the hydrogen clearance method, and
      brain tissue impedance was also measured. There was a small (up to 5-7%)
      reduction in blood flow in the first seconds of stimulation, which was followed
      15-25 sec later by an increase and subsequent return to initial when stimulation
      stopped. The increases in blood flow during stimulation of all vibrissae were by
      24.2 +/- 6.7% (n = 36) in layers IV-VI and 24.5 +/- 5.6% (n = 34) in layers I
      III; increases in response to stimulation of single vibrissae were by 19.4 +/-
      7.4% (n = 28) and 17.8 +/- 6.4% (n = 28) respectively. The dynamics of impedance
      changes corresponded to those of blood flow changes. Thus, heterogeneity was
      found in changes of local brain blood flow in different layers of the
      somatosensory cortex during increases in cortical functional activity.

PMID- 9762725
TI  - Effects of transcranial micropolarization of the frontal cortex on the state of
      motor and cognitive functions in extrapyramidal pathology.

PMID- 9762726
TI  - Mechanisms of drug transfer across the human placenta.
AB  - In this review we summarized literature data on the mechanisms of human placental
      drug transport studied in the isolated perfused placental cotyledon, placental
      membrane vesicles or trophoblastic cell cultures. Overall human placental drug
      transport rarely exceeds the transfer of flow-dependent and membrane-limited
      marker compounds. Interestingly, relatively often placental drug transfer
      appeared to be much smaller, indicating impaired trans-placental transport,
      depending on the physico-chemical characteristics of the drug or placental
      factors such as tissue binding or metabolism. Although in perfusion studies
      overall human placental drug transport occurs by simple diffusion, at the
      membrane level several drug transport systems have been found, mainly for drugs
      structurally related to endogenous compounds.

PMID- 9762727
TI  - Clinical pharmacokinetics of antimicrobial drugs in cystic fibrosis.
AB  - The disposition of many drugs in cystic fibrosis is abnormal compared with
      healthy individuals. In general, changes include an increased volume of
      distribution expressed in liters per kg bodyweight for highly hydrophilic drugs
      such as aminoglycosides, and, to a lesser extent, for penicillins and
      cephalosporins, together with an increased total body clearance. The main reason
      for the increased volume of distribution is the increased amount of lean tissue
      per kg bodyweight, since patients with CF are generally undernourished and have a
      paucity of adipose tissue. The reason for the increased renal clearance is less
      clear. Increased glomerular filtration and tubular secretion have been observed.
      Protein binding generally is unaltered in CF. The fluorquinolones and vancomycin
      show no altered pharmacokinetics in CF although gastro-intestinal absorption may
      be delayed for fluorquinolones. Sulphamethoxazole shows increased clearance due
      to an increased acetylation and, in the case of trimethoprim, renal clearance is
      increased compared with healthy individuals. As a consequence, drugs that show
      increased clearance, will lead to reduced serum concentrations and smaller AUCs
      and therefore CF patients require larger doses per kg bodyweight.

PMID- 9762728
TI  - Clinical pharmacokinetics of camptothecin topoisomerase I inhibitors.
AB  - In this review the clinical pharmacokinetics of camptothecin topoisomerase I
      inhibitors, an important new class of anticancer drugs, is discussed. Two
      prototypes, topotecan and irinotecan, are currently marketed in many European
      countries and the USA for the treatment of patients with ovarian and colorectal
      cancer, respectively. Other camptothecin derivatives, including lurtotecan, 9
      aminocamptothecin (9-AC) and 9-nitrocamptothecin (9-NC), are at different stages
      of clinical development. The common property of camptothecin analogues is their
      action against DNA topoisomerase I, but beyond this similarity the compounds
      differ widely in terms of antitumour efficacy, pharmacology, pharmacokinetics and
      metabolism. We review chemistry, mechanism of action, stability and bioanalysis
      of the camptothecins. Dosage and administration, status of clinical application,
      pharmacokinetics, pharmacodynamics and drug interactions are discussed.

PMID- 9762729
TI  - Medication control in hospitals: a practical approach to the problem of drug-drug
      interactions.
AB  - An important task of pharmacists is medication control by screening the
      medication of an individual patient. Many computerized drug interaction screening
      programs are available, but they all have their drawbacks. Screening without a
      computerized program is possible, but very time-consuming. In contrast to daily
      living at home, the patient in a hospital setting is carefully monitored and
      relevant biochemical parameters are regularly checked. Many potential drug
      interactions are countered immediately by changing (dosage of) medication. The
      aim of our study was to determine the number of drug-drug interactions and
      (pseudo)double medications on the internal, pulmonary and cardiological ward in
      order to discuss them with the physicians. During this discussion the clinical
      relevance of interactions was determined. We conclude that the number of
      clinically relevant interactions and (pseudo)double medication is limited, but
      that the role of the pharmacist is an important one, especially with regard to
      medication, that is not regularly used on a ward. Potential drug interactions
      should be predicted and dealt with by close teamwork of physician and pharmacist
      at the moment medication is prescribed.

PMID- 9762730
TI  - Evaluation of nurses' errors associated in the preparation and administration of
      medication in a pediatric intensive care unit.
AB  - The objectives of this study were to determine the frequency and the types of
      errors which occur regarding the preparation and the administration of medication
      and to identify the main causes of these errors in a pediatric intensive care
      unit (PICU) at the University Hospital in Lausanne (Switzerland). In this
      prospective study, based on the observation of nurses' activities, the data were
      collected over a period of 10 weeks. The error classification was based on the
      American Society of Hospital Pharmacy (ASHP) definitions. The frequency of errors
      was calculated as the sum of all noted errors divided by the total administered
      drugs, plus the sum of all omitted drugs, multiplied by 100. The sum of all given
      doses plus all omitted doses gives the 'total opportunity for errors'. This total
      was 275 and the total frequency of errors was 26.9%. The most frequent errors
      were wrong-time errors (32.4%), wrong-administration-technique errors (32.4%) and
      preparation errors (23.0%). In relation with other studies conducted under
      comparable conditions, a lesser number of omissions and wrong-time errors were
      observed. On the contrary, administration-technique and dose-preparation errors
      were more frequent at our hospital. A program of systematic assistance and survey
      by professional pharmacists could improve the quality of the preparation and
      administration of medication in the PICU.

PMID- 9762731
TI  - A multi-level model of data with repeated measures of the effect of lamb
      diarrhoea on weight.
AB  - Over a 1-year period, data were collected from three flocks of sheep. A total of
      213 lambs were examined routinely from birth to 32 kg (2178 examinations in
      total). Diarrhoea was seen in lambs of all ages but did not appear to make them
      systemically ill. The effect of diarrhoea on lamb weight was investigated using
      MLn, a multi-level modeling program. The data were set at three hierarchical
      levels: level one, the repeated examinations on each lamb; level two, the lamb;
      and level three, the litter. Age, the quadratic of age, litter size, sex and farm
      of origin, all had significant effect on the weight of the lambs. There was also
      significant random variation in examinations within lambs, between individual
      lambs and between litters of lambs. There was a reduction in absolute weight of
      lambs for each week until four weeks after an episode of diarrhoea.

PMID- 9762732
TI  - Prevalence of and risk factors for shedding of Cryptosporidium parvum in Holstein
      Freisian dairy calves in central Mexico.
AB  - A total of 31 dairy farms from three states in central Mexico were selected for
      this study in order to determine the prevalence of and risk factors for
      Cryptosporidium parvum shedding in young Holstein Freisian calves. Fecal samples
      were obtained once from each calf for acid-fast staining for detection of C.
      parvum oocysts. Information on each calf and on each dairy's management practices
      regarding the maternity pen, calf hutches and calf feeding was obtained by
      personal interview using a standardized questionnaire. Of the 31 dairies, 29 had
      one or more calves shedding C. parvum oocysts. The overall point prevalence was
      25% (128/512). Dairy calves from the states of Hidalgo, Jalisco, and Mexico had
      overall point prevalences of 28% (51/185), 29% (33/112) and 20% (44/215),
      respectively. Day of age was strongly associated with the risk of shedding C.
      parvum oocysts, with a maximum risk of shedding at approximately 15 days of age.
      Using mixed-effects logistic regression with herd as the random effect, feeding
      starter grain to calves, sweeping out the maternity pen, and using hay bedding in
      the maternity pen were significantly associated with increased odds of shedding
      C. parvum oocysts. We speculate that the association between feeding starter
      grain to calves and the higher odds of shedding C. parvum is linked to an
      increased duration rather than a higher incidence density of shedding. In
      addition, the association between sweeping the maternity pen and the increased
      odds of shedding C. parvum may be attributable to dairy personnel using the same
      broom for cleaning calf hutches and the maternity pen, thereby cross
      contaminating oocysts from infected to newborn calves.

PMID- 9762733
TI  - A review of the feeding-health-production complex in a dairy herd.
AB  - Diseases may be an important link in the relationship between feeding and
      production in a dairy herd. The low frequency of relevant disorders calls for
      studies on survey data on a large population. However, this approach suffers from
      lack of detailed herd feeding data and consequently only few have studied feeding
      as a risk factor for disease. Therefore, we reviewed information from various
      studies to integrate what is known of the feeding-health-production complex in a
      dairy herd. The need for putting together information from different sources, the
      herd effects, and the fact that the effect of one factor cannot be kept constant
      for investigation in a real-life dynamic herd call for a conceptual model as a
      framework for the review. The complexity is minimized to allow the representation
      of important elements. Within-cow relationships (such as feeding-disease
      relationships, disease interrelationships, and disease-production relationships)
      are reviewed specifically for: ketosis, milk fever, displaced abomasum, acidosis,
      sole ulcers and laminitis, and bloat. The major feeding management factors
      involved are concentrate feeding (level and how it is provided) and
      overconditioned cows. Disease interrelationships are important. Generalization of
      production loss from diseases is complicated due to the variety of estimates and
      measures used.

PMID- 9762734
TI  - Multiple change-point analysis applied to the monitoring of Salmonella prevalence
      in Danish pigs and pork.
AB  - In the nation-wide Salmonella Control Program in Denmark, the occurrence of
      Salmonella enterica in pork, pigs at slaughter and herds is monitored. The
      objective of the present study was to retrospectively evaluate changes in sero
      prevalence of meat juice samples and in the occurrence of Salmonella enterica in
      pork in 1995 and 1996. Three sets of data were used in this work: (1) serological
      test results of meat juice samples from pigs at slaughter (approximately 14000
      samples per week); (2) bacteriological test results of pork (approximately 550
      samples per week); and (3) data on the salmonella level of all Danish herds with
      an expected kill of over 100 pigs per year. The change-point analysis was applied
      to detect the change-points that divided the study period into intervals in which
      the prevalence was constant and to estimate the average prevalences in those
      intervals. Progress in the Danish Salmonella Control Program was visualised when
      using the results of the change-point analysis (1995-96) as baseline prevalences
      and compared with the current year (1997). The change-point analysis provided an
      indication of a seasonal pattern in salmonella occurrence with lower sero
      prevalence in summer than in winter. The sero-prevalence (percent positive meat
      juice samples) might be a better predictor of prevalence in pork than the
      proportion of herds with moderate or high sero-prevalence.

PMID- 9762735
TI  - Proportional morbidity rates of enteropathogens among diarrheic dairy calves in
      central Spain.
AB  - Faecal samples from 218 diarrheic dairy calves in 65 dairy herds, selected by
      convenience, were screened for the presence of rotavirus, coronavirus,
      Cryptosporidium spp., F5+ Escherichia coli and Salmonella spp. Animals surveyed
      were from 1 to 30 days old. Cryptosporidium and rotavirus were the most commonly
      detected agents (52.3% and 42.7% of the samples positive, respectively). F5+ E.
      coli was detected in the faeces of 11.9% of the calves and bovine coronavirus was
      detected in the faeces of 7.3% of the calves. Salmonella spp. was only found in
      the faeces of two calves (0.9%). Mixed infections with two or more agents
      occurred in 28% of the calves. Concurrent infection of rotavirus and
      Cryptosporidium was found in 21.6% of the calves. Two tests were used for the
      detection of rotavirus (a commercial ELISA and PAGE), F5+ E. coli (ELISA and
      bacterial culture) and Cryptosporidium (ELISA and microscopy). The validity of
      the commercial ELISA for the detection of rotavirus, F5+ E. coli and
      Cryptosporidium in faeces from diarrheic calves was evaluated using PAGE,
      bacterial culture and microscopy as gold standard, respectively. The ELISA showed
      a very low sensitivity (28.6%) for the detection of F5+ E. coli compared to
      bacterial culture.

PMID- 9762736
TI  - Epidemiologic features of equine Leptospira interrogans of human significance.
AB  - Leptospirosis is a zoonotic bacterial disease caused by Leptospira interrogans.
      There is a serologic evidence that horses are exposed to L. interrogans and, as a
      shedder of these organisms, can be a threat to humans. We examined risk factors
      associated with the risk of testing seropositive to three L. interrogans serovars
      (L. icterohaemorrhagiae, L. grippotyphosa, and L. canicola) in the horses of New
      York State, in order to understand the epidemiology of the disease and suggest
      strategies to control and prevent equine leptospirosis. To carry out this study,
      blood samples were collected from a random sample of 2551 horses and tested for
      the presence of antibodies to the above serovars using the microscopic
      agglutination test. Samples with a titer $100 were considered positive. Clinical
      and demographic data were collected on each horse, the farms' management
      practices and ecology. Logistic regression analysis was used to develop a
      multivariate indexing system and to identify factors significantly associated
      with the risk of leptospirosis. Four indices were developed based on the possible
      sources of exposure: rodent exposure index; wildlife exposure index; soil and
      water index; and management index. The soil and water index was significantly
      associated with the risk of exposure to all three serovars. Management was
      positively associated with L. icterohaemorrhagiae and L. canicola. Density of
      horses turned out together was positively associated with the risk of exposure to
      L. grippotyphosa. We concluded that indirect exposure of horses to L. interrogans
      through contaminated soil and water appears to be significantly associated with
      the risk of exposure to all three serovars. Management appears to play an
      important role in the exposure to L. interrogans. Modification of management
      practices might reduce the horses' risk of exposure and hopefully minimize the
      human hazards.

PMID- 9762738
TI  - A biomechanical study of anterior thoracolumbar screw fixation.
AB  - STUDY DESIGN: The pullout strength of unicortical and bicortical screws in
      thoracic and lumbar vertebral bodies was measured as a function of bone mineral
      density. OBJECTIVES: To determine the influence of bone mineral density and screw
      insertion technique on the stability of anterior thoracolumbar spine screw
      fixation. SUMMARY OF BACKGROUND DATA: No previous study has addressed the
      specific technique of screw insertion or stability of screw fixation in the
      anterior spine. METHODS: Fifty-one human thoracic vertebral bodies were tested in
      pullout with 6.55-mm cancellous screws inserted using unicortical and bicortical
      techniques. RESULTS: Pullout force increased exponentially with increasing bone
      mineral density for unicortical and bicortical screws. Bicortical screws were
      significantly stronger in resisting pullout than unicortical screws. CONCLUSION:
      Advancing an anterior vertebral body screw to engage the second cortex increases
      resistance to pullout by 25-44%, depending on vertebral bone mineral density. The
      difference in resistance between unicortical and bicortical techniques was
      smaller in specimens with low mineral densities.

PMID- 9762737
TI  - A new culture system to study the metabolism of the intervertebral disc in vitro.
AB  - STUDY DESIGN: This study determined whether entrapment of a rabbit intervertebral
      disc in alginate gel helped to promote the retention of normal metabolic
      activities by the nucleus pulposus and anulus fibrosus in tissue culture.
      OBJECTIVES: To establish an in vitro culture system to study the metabolism of
      the intervertebral disc as a whole integral organ. SUMMARY OF BACKGROUND DATA: In
      vitro studies of the metabolism of intervertebral discs have been scarce because
      of the difficulties involved in maintaining the integrity of the tissues,
      especially that of the nucleus pulposus, in culture medium. METHODS: Rabbit
      intervertebral discs were embedded in alginate gel and maintained in culture for
      as long as 1 month. At weekly intervals, experiments were performed to measure
      the rate of proteoglycan synthesis and to characterize proteoglycans newly
      synthesized by cells in the anulus fibrosus and nucleus pulposus. In addition, at
      these same time intervals, the contents of sulfated proteoglycans, antigenic
      keratan sulfate, hyaluronan, and collagen in these two intervertebral disc
      tissues were measured to evaluate tissue integrity. Intervertebral discs cultured
      in medium alone were used as controls and analyzed in parallel. RESULTS: The
      anulus fibrosus and nucleus pulposus of intervertebral discs cultured in alginate
      gel sustained a higher rate of proteoglycan synthesis and maintained a higher
      content of extracellular matrix components than the respective controls at all
      times. CONCLUSIONS: This new alginate tissue culture system should prove useful
      for studying the metabolism of whole intervertebral discs.

PMID- 9762739
TI  - A biomechanical study of Jefferson fractures.
AB  - STUDY DESIGN: Fifteen specimens of the first cervical vertebra were tested by the
      application of pure tensile forces to failure. Seven specimens had intact
      transverse ligaments, and eight had transection of the transverse ligament before
      testing. Specimens were tested to failure by the rapid application of laterally
      directed tensile force to the ring; this force then was exerted through the
      lateral masses to simulate the mechanism of injury for this fracture as proposed
      by Jefferson. OBJECTIVES: To measure the biomechanical characteristics of the C1
      ring, including the fracture patterns created with tensile loading, and to
      describe the influence of the transverse ligament on the behavior of the ring as
      it failed under tension. SUMMARY OF BACKGROUND DATA: Jefferson fractures have
      been reproduced in the laboratory by subjecting head and neck preparations to
      axial load. However, no previous detailed biomechanical studies of the fracture
      characteristics of the isolated C1 vertebra have been reported. METHODS:
      Specimens were tested to failure by rapid application of laterally directed
      tensile forces to the ring. RESULTS: Eleven two-part and three three-part
      fractures occurred. The mean tensile strength of the atlas was found to be 2,280
      N. The average deformation required to fracture the C1 ring was 1.57 mm. The
      total energy absorbed by the ring averaged 1.99 N-m. There was no statistically
      difference between those specimens with the transverse ligament intact and those
      without a transverse ligament. CONCLUSIONS: The results of this study show that
      fractures of the C1 ring of greater than two parts can occur with pure tensile
      loading. The ring will fracture with as little as 1 mm of deformation.

PMID- 9762740
TI  - Functional outcome of surgically and conservatively managed dens fractures.
AB  - STUDY DESIGN: Fifty-seven patients with dens fractures were identified from 1986
      to 1996 at the authors' institution. Forty-six were available for reevaluation by
      two independent observers with a mean follow-up period of 26 months. OBJECTIVE:
      To determine by age and fracture type which treatment regimen provided the best
      functional outcome in patients with dens fractures. SUMMARY OF BACKGROUND DATA:
      There were no Type I fractures, but there were 37 Type II and 20 Type III
      fractures. Twenty-nine patients were under 60 years of age, and 28 were 60 years
      and older. Six patients had been treated by immediate C1-C2 posterior fusion, and
      five received treatment with a Philadelphia collar only. Forty-six patients were
      placed in a halo thoracic immobilizer with a symptomatic nonunion rate of 19.5%.
      These patients ultimately required posterior cervical fusion. METHODS: Final
      functional outcome, level of pain, and cervical range of motion were all
      statistically evaluated using multivariate analysis (Wilcoxon's two-sample test).
      The influence of age, fracture type, and treatment method were determined.
      RESULTS: There were no cases of short- or long-term neurologic deterioration in
      any of the patients in the study group. There was a significantly higher rate of
      complications associated with halo use in the older population. Pain scores were
      higher in Type II fractures and in patients treated conservatively with halo
      immobilization, especially those patients over 60 years of age. No statistically
      significant difference in these parameters were found. Older patients treated
      surgically did not have a better functional outcome score than those treated
      nonoperatively (P < 0.8). Persons over 60 years of age treated in a halo had a
      significantly (P < 0.05) decreased range of motion when compared with younger
      patients treated similarly. CONCLUSION: Patients over 60 years of age with a dens
      fracture had a higher complication rate and lower cervical range of motion when
      treated conservatively with a halo. Final functional outcome and overall pain
      levels, however, did not differ significantly by age group or treatment modality.

PMID- 9762741
TI  - The ability of lumbar medial branch blocks to anesthetize the zygapophysial
      joint. A physiologic challenge.
AB  - STUDY DESIGN: Randomized, controlled, single blinded study. OBJECTIVES: To
      determine the physiologic effectiveness of lumbar medial branch blocks. SUMMARY
      OF BACKGROUND DATA: Zygapophysial joint pain can be diagnosed by anesthetization
      of the joint or its nerve supply (the medial branch divisions of the dorsal
      rami). The physiologic effectiveness of lumbar medial branch blocks has been
      assumed but not proven. METHODS: Eighteen asymptomatic individuals were randomly
      assigned to either L4-L5 or L5-S1 zygapophysial joint injections with contrast
      medium until capsular distention elicited pain without extracapsular contrast
      spread. One week later, 15 blinded individuals underwent two randomized saline or
      2% lidocaine medial branch injections that correlated to the innervation of the
      previously injected joint. Medical branch injections were performed such that
      inadvertent venous uptake was avoided in 14 individuals. Thirty minutes after
      medial branch injections, these 14 individuals underwent repeat capsular
      distention of the same zygapophysial joint provoked the prior week in an attempt
      to elicit another painful response. RESULTS: All five control individuals who
      received saline medial branch injections felt pain on repeat capsular distention.
      Nine individuals received 2% lidocaine medial branch blocks; eight felt no pain,
      and one felt pain on repeat capsular distention. CONCLUSIONS: There was a
      significant effect of 2% lidocaine (versus saline) medial branch injections on
      anesthetization of the zygapophysial joint when venous uptake was avoided during
      these injections. When properly performed, lumbar medial branch blocks
      successfully inhibit pain associated with capsular distention of the lumbar
      zygapophysial joints at a rate of 89%.

PMID- 9762742
TI  - Regional correspondence between the ventral portion of the lumbar intervertebral
      disc and the groin mediated by a spinal reflex. A possible basis of discogenic
      referred pain.
AB  - STUDY DESIGN: Lumbar peripheral nerves were examined to determine whether they
      were responsive to electrical stimulation of the ventral portion of the lumbar
      disc in anesthetized rats. OBJECTIVES: To confirm by electrophysiologic means the
      neural correspondence between the ventral portion of the lumbar disc and the
      groin. SUMMARY OF BACKGROUND DATA: Patients with a degenerated lumbar disc
      occasionally report groin pain. However, its pathogenesis has not been
      investigated. The authors of the current study found that chemical stimulation of
      the ventral portion of rat lumbar disc caused cutaneous plasma extravasation in
      the groin, and thereby hypothesize the neural relation between the lumbar disc
      and the groin. METHODS: The ventral portion of rat L5-L6 disc was electrically
      stimulated, and the elicited action potentials were recorded from the
      iliohypogastric, genitofemoral, lateral femoral cutaneous, sural, and sciatic
      nerves. The roles of the lumbar sympathetic trunks and spinal cord in the
      generation of the action potentials were examined. RESULTS: Action potentials
      were elicited principally in the genitofemoral nerve; the action potentials of
      the genitofemoral nerve were not influenced by transection of the cervical spinal
      cord, whereas they disappeared immediately after death, which indicates that they
      are induced by a spinal reflex. The action potentials were reduced considerably
      after destruction of the lumbar sympathetic trunks, suggesting that they comprise
      an afferent path of the reflex. CONCLUSIONS: The ventral portion of the lumbar
      disc had spatial relation to the groin area via a spinal reflex. Such a relation
      suggests that a disorder in the ventral portion of the lumbar disc may be a
      possible source of groin referred pain.

PMID- 9762743
TI  - The Saskatchewan health and back pain survey. The prevalence of low back pain and
      related disability in Saskatchewan adults.
AB  - STUDY DESIGN: Population-based, cross-sectional, mailed survey. OBJECTIVES: To
      determine the lifetime, 6-month period, and point prevalence of low back pain and
      its related disability among Saskatchewan adults and to investigate the presence
      and strength of selective response bias. SUMMARY OF BACKGROUND DATA: There have
      been many reports of the prevalence of low back pain in different populations,
      and the estimates vary widely depending on case definition. However, most studies
      fail to differentiate between trivial and disabling back pain, which raises the
      issue of the usefulness of these estimates. No studies have yet documented the
      prevalence of graded low back pain severity and its related disability in a North
      American, general, population-based survey. METHODS: The Saskatchewan Health and
      Back Pain Survey was mailed to a probability sample of 2184 Saskatchewan adults
      between 20 and 69 years of age. Fifty-five percent of the eligible population
      responded to the survey. Respondents were compared with nonrespondents, and the
      presence of selective response bias by back pain status was investigated by wave
      analysis. The point and lifetime prevalence of low back pain was determined by
      simple questions, and the 6-month period prevalence of low back pain was
      determined by the Chronic Pain Questionnaire. All estimates were age standardized
      to the Saskatchewan population. RESULTS: The authors estimate that at the time of
      the survey 28.4% (95% confidence interval, 25.6-31.1) of the Saskatchewan adult
      population were experiencing low back pain, and 84.1% (95% confidence interval,
      81.9-86.3) had experienced it during their lifetime. Overall, 48.9% (95%
      confidence interval, 45.9-52.0) of the population had experienced low
      intensity/low-disability low back pain in the previous 6 months, 12.3% (95%
      confidence interval, 10.3-14.4) had experienced high-intensity/low-disability low
      back pain, and an additional 10.7% (95% confidence interval, 8.8-12.5) had
      experienced high-disability low back pain in the previous 6 months. There was
      little variation in the estimates over age groups, but women experienced more
      high-disability back pain than men. There was no evidence of selective response
      bias by low back pain status in the survey. CONCLUSION: Low-intensity/low
      disability low back pain is a common problem in the general population.
      Approximately 11% of the adult population studied had been disabled by low back
      pain in the previous 6 months.

PMID- 9762744
TI  - Degenerative displacement of lumbar vertebrae. A 25-year follow-up study in
      Framingham.
AB  - STUDY DESIGN: The authors assessed degenerative lumbar displacement in a
      population-based cohort of 217 men and 400 women who had lateral lumbar
      radiographs performed at the mean age of 54 years and again at 79 years, and who
      had completed interviews on back symptoms and functional performance in
      connection with the follow-up examination. OBJECTIVES: To assess the prevalence
      and incidence of degenerative slippage and its association with back pain and
      physical disability. SUMMARY OF BACKGROUND DATA: Degenerative displacement of
      lumbar vertebrae may cause instability, nerve root compression, and spinal
      stenosis. Its incidence in the older population and association with back pain
      and disability are unknown. METHODS: The authors assessed the prevalence and
      incidence of degenerative slippage from lateral lumbar radiographs performed 25
      years apart and its association with back pain and physical disability from
      interviews performed in connection with the follow-up examination. RESULTS: At
      the follow-up examination, 23 (12%) men and 100 (25%) women had developed
      degenerative slippage exceeding 3 mm; two of them had this already at the
      baseline. A forward displacement was found in 8 men and 76 women (P < 0.0001 for
      difference between the genders) and a backward one in 16 men and 35 women. On
      average, forward slip was 18% +/- 5.5, and backward slip, 15% +/- 4.0 of the
      anteroposterior diameter of the vertebra below. At the time of the second lumbar
      radiograph, 39 (32%) of the subjects with slippage, compared with 90 (19%) of the
      controls, had pain, aching, or stiffness in their back on most days (P = 0.001).
      After adjustment for endplate sclerosis, which was also related to pain (P =
      0.015), slippage still had association with daily back symptoms (P = 0.009).
      However, subjects with slippage had not experienced more back symptoms during the
      preceding year or in earlier ages of life, and they did not report more
      disability than the controls. CONCLUSIONS: Degenerative displacement of lumbar
      vertebrae is common in an older population and is associated with increased
      prevalence of daily back symptoms. However, two thirds of the subjects with
      degenerative displacement do not report ongoing back symptoms, and the disorder
      is also unrelated to long-term back pain and physical disability.

PMID- 9762745
TI  - One-year follow-up comparison of the cost and effectiveness of chiropractic and
      physiotherapy as primary management for back pain. Subgroup analysis, recurrence,
      and additional health care utilization.
AB  - STUDY DESIGN: A randomized trial was conducted in which patients with back and
      neck pain, visiting a general practitioner, were allocated to chiropractic or
      physiotherapy. OBJECTIVES: To compare outcome and costs of chiropractic and
      physiotherapy as primary treatment for patients with back and neck pain, with
      special reference to subgroups, recurrence rate, and additional health care use
      at follow-up evaluation 12 months after treatment. SUMMARY OF BACKGROUND DATA:
      Earlier studies on the effect of spinal manipulation have shown inconsistent
      results. Mostly they include only short-term follow-up periods, and few cost
      effectiveness analyses have been made. METHODS: A group of 323 patients aged 18
      60 years who had no contraindications to manipulation and who had not been
      treated within the previous month were included. Outcome measures were changes in
      Oswestry scores, pain intensity, and general health; recurrence rate; and direct
      and indirect costs. RESULTS: No differences were detected in health improvement,
      costs, or recurrence rate between the two groups. According to Oswestry score,
      chiropractic was more favorable for patients with a current pain episode of less
      than 1 week (5%) and physiotherapy for patients with a current pain episode of
      greater than 1 month (6.8%). Nearly 60% of the patients reported two or more
      recurrences. More patients in the chiropractic group (59%) than in the
      physiotherapy group (41%) sought additional health care. Costs varied
      considerably among individuals and subgroups; the direct costs were lower for
      physiotherapy in a few subgroups. CONCLUSIONS: Effectiveness and costs of
      chiropractic or physiotherapy as primary treatment were similar for the total
      population, but some differences were seen according to subgroups. Back problems
      often recurred, and additional health care was common. Implications of the result
      are that treatment policy and clinical decision models must consider subgroups
      and that the problem often is recurrent. Models must be implemented and tested.

PMID- 9762746
TI  - Sequential or simultaneous, same-day anterior decompression and posterior
      stabilization in the management of vertebral osteomyelitis of the lumbar spine.
AB  - STUDY DESIGN: A retrospective clinical study of patients with vertebral
      osteomyelitis of the lumbar spine necessitating surgical treatment. All patients
      underwent sequential (same-day) or simultaneous anterior decompression and
      posterior stabilization of the involved vertebrae. OBJECTIVE: To evaluate the
      efficacy and clinical out-come of sequential or simultaneous anterior and
      posterior surgical approaches in the management of vertebral osteomyelitis of the
      lumbar spine. SUMMARY OF BACKGROUND DATA: Anterior approach alone and staged
      anterior decompression and posterior stabilization have been advocated as the
      surgical treatment methods of choice for patients with vertebral osteomyelitis of
      the lumbar spine. The drawbacks of the latter management plan are the necessity
      to use external support or the delayed patient mobilization and the need for
      additional anesthesia and surgical trauma. Sequential (same-day) anterior and
      posterior approaches are used regularly in the surgical management of scoliosis
      and other spinal deformities. It would appear advantageous to also use the same
      strategy (i.e., combined same-day double approaches) in the management of
      vertebral osteomyelitis of the lumbar spine. METHODS: Ten consecutive patients
      who had a diagnosis of vertebral osteomyelitis of the lumbar spine underwent
      combined (same-day) anterior and posterior approaches either in a sequential or
      simultaneous manner. Indications for surgery included neurologic deficit, abscess
      formation, instability with localized kyphosis formation, and failure of
      nonoperative treatment. Patients were evaluated clinically and radiographically
      after surgery. RESULTS: All 10 patients had uneventful surgery. Only one patient
      required a second surgical procedure because of expulsion of the anterior bone
      graft and pull-out of instrumentation. All patients were mobilized within the 2
      days immediately after surgery. At the mean follow-up examination 30 months after
      surgery, all patients had regained their motor function and prior ambulatory
      status. CONCLUSIONS: Patients with lumbar osteomyelitis necessitating surgery can
      undergo combined, same-day surgery either in a sequential or simultaneous manner.
      This is a safe and efficient way to control the infection and stabilize the
      affected segments, allowing for early mobilization of these sick elderly
      patients.

PMID- 9762747
TI  - L5 root compression caused by degenerative spinal stenosis of the L1-L2 and L2-L3
      spaces.
AB  - STUDY DESIGN: A severe bilateral L5 root lesion associated with spinal stenosis
      at L1-L2 and L2-L3 is described. OBJECTIVE: To describe clinical findings and the
      difficulty in obtaining a correct diagnosis of L5 Root Compression. SUMMARY OF
      BACKGROUND DATA: The disorder reported in this study has not been reported
      previously. Only one similar case has been described in the literature: an L5
      root compression at L1-L2 caused by disc herniation. METHODS: Diagnosis was
      obtained by using computed tomography scanning, magnetic resonance imaging, and
      computed tomography myelography. The findings at L5-S1 were minimal to justify
      the patient's clinical symptoms, but a detailed study of the upper levels
      revealed spinal stenosis at L1-L2 and L2-L3, which could have been causing L5 and
      S1 root compression. A decompressive laminectomy and partial facetectomy in both
      levels were performed. RESULTS: The patient's pain and claudication disappeared,
      and clinical symptoms associated with the right L5 root improved. The left L5
      root deficit remained stable. CONCLUSION: An unusual case of L5 root compression
      caused by degenerative stenosis of L1-L2 and L2-L3 is described.

PMID- 9762749
TI  - Costal osteochondroma. A rare cause of spinal cord compression.
AB  - STUDY DESIGN: Report of a rare cause of spinal cord compression: costal
      osteochondroma. OBJECTIVE: To describe a very rare cause of spinal cord
      compression, costal osteochondroma, which was present in a 16-year-old girl with
      a history of hereditary multiple exostoses. SUMMARY OF BACKGROUND DATA: Only four
      cases of expansion of costal osteochondroma into the spinal canal through an
      intervertebral foramen have been reported previously. METHODS AND RESULTS: The
      origin of the osteochondroma at the head of the right 12th rib, the invasion of
      the spinal canal through the right T12-L1 intervertebral foramen, and the
      compression of the spinal cord were shown on computed tomography and magnetic
      resonance imaging. The exact extent of the osteochondroma, particularly the
      cartilage cap, was delineated accurately by magnetic resonance imaging. Complete
      excision followed by full recovery occurred 19 months after surgery. CONCLUSION:
      Magnetic resonance imaging is the preferred method of investigation in cases of
      osteochondroma related to spine, because it allows for better pre-operative
      planning and helps to prevent incomplete excision of the tumor.

PMID- 9762748
TI  - Lumbar intervertebral disc involvement in chronic lymphocytic leukemia. A case
      report.
AB  - STUDY DESIGN: Report of a patient with a rare location of a solid chronic
      lymphocytic leukemic mass of an intervertebral lumbar disc. OBJECTIVES: To
      illustrate the previously undescribed discovertebral involvement of chronic
      lymphocytic leukemia and to discuss the diagnostic difficulties. SUMMARY OF
      BACKGROUND DATA: Chronic lymphocytic leukemia primarily involves lymph nodes,
      spleen, liver, and bone marrow. Bone lesions are rare in chronic lymphocytic
      leukemia and usually consist of areas of osteopenia. Spinal involvement in
      chronic lymphocytic leukemia is rare, and only two cases of spinal cord
      compression attributable to an extradural solid mass composed of leukemic cells
      have been reported. Intervertebral disc involvement in chronic lymphocytic
      leukemia has not been reported previously. METHODS: The clinical findings,
      radiographs, histology, treatment, and follow-up results are presented. RESULTS:
      Radiographs and magnetic resonance imaging studies showed partial collapse of
      vertebrae L2 and L3, with destruction and protrusion of the intervertebral disc
      L2-L3 with dura compression. Treatment consisted of radiotherapy followed by en
      bloc resection of vertebrae L2 and L3 stabilized with stackable cages and
      anterior fixation with Kaneda bars. Intervertebral disc infiltration with
      leukemic cells of B-cell origin was confirmed through histologic examination and
      immunohistochemical studies of a biopsy and resection specimen. Twenty months
      after treatment the patient was still in remission and fully mobilized.
      CONCLUSIONS: Intervertebral disc involvement in cases of chronic lymphocytic
      leukemia is rare. Its presence should be considered in patients with back pain
      and neurologic symptoms who had been treated for this form of leukemia in the
      past. Differentiation with infectious spondylodiscitis can be difficult.
      Histology is necessary to confirm diagnosis.

PMID- 9762751
TI  - Intraoperative electromyography during thoracolumbar spinal surgery.
AB  - Intraoperative electromyography can provide useful information regarding
      lumbosacral nerve root function during thoracolumbar spinal surgery. Free-running
      electromyography provides continuous feedback regarding the location and
      potential for surgical injury to the lumbosacral nerve roots within the operative
      field. Stimulus-evoked electromyography can confirm that transpedicular
      instrumentation has been positioned correctly within the bony cortex. However,
      electromyography has a number of potential limitations, which are discussed in
      this article along with improved methods to increase the overall efficacy of
      intraoperative electromyography, including: 1) Electromyography is sensitive to
      blunt lumbosacral nerve root irritation or injury, but may provide misleading
      results with "clean" nerve root transection. 2) Electromyography must be recorded
      from muscles belonging to myotomes appropriate for the nerve roots considered at
      risk from surgery. 3) Electromyography can be effective only with careful
      monitoring and titration of pharmacologic neuromuscular junction blockade. 4)
      When transpedicular instrumentation is stimulated, an exposed nerve root should
      be stimulated directly as a positive control whenever possible. 5) Pedicle holes
      and screws should be stimulated with single shocks at low-stimulus intensities
      when pharmacologic neuromuscular blockade is excessive. 6) Chronically compressed
      nerve roots that have undergone axonotmesis (wallerian degeneration) have higher
      thresholds for activation from electrical and mechanical stimulation. 7) Hence,
      whenever axonotmetic nerve root injury is suspected, the stimulus thresholds for
      transpedicular holes and screws must be specifically compared with those required
      for the direct activation of the adjacent nerve root (and not published guideline
      threshold values).

PMID- 9762750
TI  - Herophilus of Alexandria (325-255 B. C.). The father of anatomy.
AB  - Herophilus (325-255 B. C.) is one of the group that has been called the great
      Greek physicians. All members of this group lived during the last 400 years of
      Greek intellectual leadership and the first 200 years of Roman domination.
      Herophilus was born in the Greek town of Chalcedon. He received his medical
      training under Praxagoras, a famous physician and anatomist who taught at the
      Hippocratean medical school on the island of Cos (Kos). He moved to Alexandria,
      Egypt, as a young man and lived there for the rest of his life. With his younger
      contemporary, Erasistratus, he did the first ever scientific human cadaveric
      dissections for a short period of no more than 30-40 years. Human dissection then
      was forbidden and was not allowed again for 1800 years. It seems that only these
      two physicians ever performed human dissection until the Renaissance, around 1530
      A. D. The anatomic and physiologic discoveries of Herophilus were phenomenal. As
      Hippocrates is called the Father of Medicine, Herophilus is called the Father of
      Anatomy. Most would argue that he was the greatest anatomist of antiquity and
      perhaps of all time. The only person who might challenge him in this assessment
      is Vesalius, who worked during the 16th century A. D.

PMID- 9762752
TI  - Saskatchewan health and back pain survey.

PMID- 9762753
TI  - Lumbar lordosis: effects of sitting and standing.

PMID- 9762754
TI  - Postoperative pain control after lumbar spine fusion.

PMID- 9762755
TI  - Observations made during school screening for scoliosis in Greece.

PMID- 9762756
TI  - Milk quality survey to include Mycobacterium paratuberculosis.

PMID- 9762757
TI  - Effects of quarantine on cats and their owners.
AB  - The effects of quarantine on 16 cats and their owners were assessed by means of
      four questionnaires completed by the owners at the beginning of their cat's stay
      in quarantine, three months later, and two weeks and three months after the cats
      left quarantine. Changes in body condition were evident in two-thirds of the cats
      during and at the end of quarantine but not three months later. Mid-way through
      quarantine, the owners considered their cats were less attached to them, less
      relaxed, more excitable, more aggressive, more nervous and less playful than
      before quarantine. When they left quarantine the cats were friendlier, more
      affectionate and more timid, and three months later they were more affectionate,
      more nervous and more vocal than before quarantine. When they left quarantine and
      three months later the cats spent more time with their owners than before
      quarantine. Most owners visited their cats once or twice a month; the location of
      the cattery and the limited opening hours restricted the number of visits they
      made.

PMID- 9762758
TI  - Comparison of pethidine, buprenorphine and ketoprofen for postoperative analgesia
      after ovariohysterectomy in the cat.
AB  - Sixty cats which underwent an ovariohysterectomy were randomly allocated into
      four treatment groups. One group (controls) received no analgesics
      postoperatively, and the others received either a single dose of buprenorphine
      (0.006 mg/kg) intramuscularly, or pethidine (5 mg/kg) intramuscularly, or
      ketoprofen (2 mg/kg) subcutaneously. The analgesia obtained after each treatment
      was assessed by three measures. There were significant differences between the
      groups both for the requirement for intervention analgesia (P = 0.0008) and for
      the overall clinical assessment (P = 0.0003) with ketoprofen requiring least
      intervention analgesia and having the best overall clinical assessment, followed
      by buprenorphine then pethidine. The control group required the most intervention
      analgesia and had the worst overall clinical assessment. Visual analogue scale
      scoring for pain produced significant differences between the groups from one
      hour after the operation, with the cats which were given ketoprofen tending to
      have lower pain scores than the other groups.

PMID- 9762759
TI  - Inhibition of antigen-induced cutaneous responses of ponies with insect
      hypersensitivity by the histamine-1 receptor antagonist chlorpheniramine.
AB  - A whole-body extract of Culicoides impunctatus induced a biphasic increase in
      oedema formation in ponies with insect hypersensitivity, with maxima after one
      and eight hours. The Culicoides antigen did not induce similar responses in
      ponies with no previous history of the disease. In insect-hypersensitive ponies
      the local administration of chlorpheniramine (12 micrograms) completely inhibited
      oedema formation in response to histamine (0.04 microgram) and to Culicoides
      antigen (0.5 microgram) at one hour, and the response to Culicoides antigen at
      eight hours was inhibited by 63 per cent. Chlorpheniramine also partially
      inhibited the accumulation of eosinophils and neutrophils induced by Culicoides
      antigen after two hours.

PMID- 9762760
TI  - Persistence of the activity of topical ivermectin against biting lice (Bovicola
      bovis).
AB  - To assess the persistence of the activity of topical ivermectin against a natural
      challenge with biting lice (Bovicola bovis), 90 mixed-breed cattle that had been
      treated to remove lice, were blocked by bodyweight within sex and randomly
      allocated to three treatments: untreated control, doramectin at 200 micrograms/kg
      by subcutaneous injection, and ivermectin at 500 micrograms/kg by topical
      application. Forty-five pens were blocked into three groups of 15, and the blocks
      of pens were randomly allocated to three 14-day challenge periods starting 21, 28
      and 35 days after treatment. There were five pens per treatment for each
      challenge period, and one B bovis-infested donor calf was introduced into each
      pen containing two principal calves at the start of the challenge period for that
      block of pens. The calves were examined thoroughly for B bovis seven, 14 and 21
      days after the introduction of the donors. There were no significant differences
      between the control and doramectin groups for the numbers of animals infested, or
      the geometric mean louse counts at the final examination for any of the challenge
      periods. At the final examination for each challenge period, the louse counts of
      the cattle treated with topical ivermectin were all zero, and significantly (P <
      0.05) fewer cattle treated with topical ivermectin were infested than either the
      controls or cattle treated with doramectin.

PMID- 9762761
TI  - Laryngeal rhabdomyoma in a golden retriever.
AB  - A three-year-old male golden retriever had had progressive dyspnoea, exercise
      intolerance, stridor, and a modified bark for five months. A mass 2 cm in
      diameter was present dorsal to the right side of the larynx. Histological
      examination revealed cross-striations in some elongated cells, consistent with a
      diagnosis of rhabdomyoma, a diagnosis which was confirmed by positive
      immunohistochemical staining for myoglobin and desmin. The mass could not be
      removed without total laryngectomy and a permanent tracheostomy and the dog was
      euthanased.

PMID- 9762762
TI  - Influence of concurrent BVDV infection on the IgM response of calves
      experimentally infected with bovine respiratory syncytial virus.

PMID- 9762763
TI  - Natural reactivation of caprine herpesvirus 1 in latently infected goats.

PMID- 9762764
TI  - Congenital stenosis of the preputial orifice in a dog.

PMID- 9762765
TI  - BVPA guidelines on antimicrobial resistance.

PMID- 9762767
TI  - Importance of personal insurance.

PMID- 9762766
TI  - Recall of Droplix.

PMID- 9762768
TI  - Homoeopathy and clinical trials.

PMID- 9762769
TI  - 'Twitchiness' in miniature wirehaired dachshunds.

PMID- 9762770
TI  - What is your diagnosis?

PMID- 9762771
TI  - Being more positive about negative ventilation?

PMID- 9762772
TI  - Immunoglobulin A in asthma: friend or foe?

PMID- 9762773
TI  - Negative pressure ventilation versus conventional mechanical ventilation in the
      treatment of acute respiratory failure in COPD patients.
AB  - This case-control study was aimed to evaluate the effectiveness of negative
      pressure ventilation (NPV) versus conventional mechanical ventilation (CMV) for
      the treatment of acute respiratory failure (ARF) in patients with chronic
      obstructive pulmonary disease (COPD) admitted to a respiratory intermediate
      intensive care unit (RIICU) and four general intensive care units (ICU). Twenty
      six COPD patients in ARF admitted in 1994-95 to RIICU and treated with NPV
      (cases) were matched according to age (+/-5 yrs), sex, causes triggering ARF,
      Acute Physiology and Chronic Health Evaluation (APACHE) II score (+/- 5 points),
      pH (+/-0.05) and arterial carbon dioxide tension (Pa,CO2) on admission with 26
      patients admitted to ICU and treated with CMV (controls). The primary end points
      of the study were inhospital death for both groups and the need for endotracheal
      intubation for cases. The secondary endpoints were length and complications of
      mechanical ventilation and length of hospital stay. The effectiveness of matching
      was 91%. Mortality rate was 23% for cases and 27% for controls (NS), five cases
      needed endotracheal intubation, four of whom subsequently died. The duration of
      ventilation in survivors was significantly lower in cases than in controls, with
      a median of 16 h (range 2-111) versus 96 h (range 12-336) (P<0.02), whereas the
      length of hospital stay was similar in the two groups, with a median of 12 days
      (range 2-47) for cases vs 12 days (range 3-43) (NS) for controls. No
      complications were observed in cases, whereas three controls developed infective
      complications. These results suggest that negative pressure ventilation is as
      efficacious as conventional mechanical ventilation for the treatment of acute
      respiratory failure in patients with chronic obstructive pulmonary disease and
      that it is associated with a shorter duration of ventilation and a similar length
      of hospital stay compared with conventional mechanical ventilation.

PMID- 9762774
TI  - Measurement of overinflation by multiple linear regression analysis in patients
      with acute lung injury.
AB  - Strategies to optimize alveolar recruitment and prevent lung overinflation are
      central to ventilatory management of patients with acute lung injury (ALI). The
      recent description of overinflation using multilinear regression analysis of
      airway pressure (Paw) and flow (V') data allows a functional assessment of lung
      mechanics. However, this technique has not been studied in ALI patients. During
      15 positive end-expiratory pressure (PEEP) trials in 10 ALI patients, respiratory
      elastance was partitioned into volume-independent (E1) and volume-dependent
      (E2VT) components, where Paw=(E1+E2VT)V+RrsV'+Po; where V is volume, VT is tidal
      volume, Rrs is respiratory resistance and Po is static recoil pressure at end
      expiration (equivalent to total PEEP). Then, %E2 was calculated as
      (100E2VT)/(E1+E2VT); a measure of lung overinflation when %E2>30%. Alveolar
      recruitment, assessed as a PEEP-induced increase in V>50 mL at a constant Paw
      occurred in 14 of 15 trials (299+/-34 mL, mean+/-SEM), but was independent of the
      degree of lung inflation. Lung overinflation was common (six of 15 clinically set
      PEEP levels) and occurred despite a dynamic elastic distending pressure (Pel,dyn)
      <30 cmH2O during 18 of 36 PEEP titrations. During a PEEP titration the resultant
      %E2 was directly related to delta(peak airway pressure-Po) (rs=0.86, p<0.001) and
      delta(Pel,dyn-Po) (rs=0.89, p<0.001). The 95% predictive intervals for a 2 cmH2O
      change in either driving pressure were %E2 values of 30.4-68.1% and 32.8-69.2%,
      respectively. Single or continuous measurement of %E2 (a measure of lung
      inflation) is a readily available method for titrating ventilatory parameters.
      Further, during a positive end-expiratory pressure titration a change in
      ventilatory driving pressure > or =2 cmH2O is indicative of overinflation.

PMID- 9762775
TI  - Efficacy of Curosurf in a rat model of acute respiratory distress syndrome.
AB  - Curosurf, a natural lung surfactant, is considered a potential candidate for
      improving the treatment of acute respiratory distress syndrome (ARDS). To
      investigate this in a rat model of early-stage ARDS, Curosurf (62.5, 125 or 250
      mg x kg(-1)) was administered by intratracheal bolus at 10 or 24 h following an
      intratracheal lipopolysaccharide (LPS; 1.6 mg x kg(-1)) challenge. Survival,
      respiratory frequency (fR), lung wet weight (LWW), total protein and cell
      differentiation in bronchoalveolar lavage fluid (BALF) were assessed. Curosurf
      treatment at 10 h after LPS challenge resulted in 100% survival at both 62.5 and
      125 mg x kg(-1); at a dose of 250 mg x kg(-1) administered at 10 h after LPS, 1
      out of 6 animals died. At a dose of 125 mg x kg(-1) Curosurf administered at 24 h
      after LPS, 1 out of 6 animals died. In contrast, only 35% of animals survived
      when not treated with Curosurf. Curosurf treatment resulted in an improved fR and
      in a significantly decreased LWW, total protein and number of polymorphonuclear
      cells in BALF. In conclusion, Curosurf treatment improved respiratory frequency
      and decreased mortality, pulmonary oedema and inflammation. As the decreased
      mortality was observed in spontaneously breathing nonoxygenated animals, the
      results cannot be extrapolated to human artificially ventilated acute respiratory
      distress syndrome patients with the expectation of a decreased mortality. The
      results suggest, however, that Curosurf may be an important therapeutic measure
      in early-stage acute respiratory distress syndrome.

PMID- 9762776
TI  - Elevation of specific immunoglobulin A antibodies to both allergen and bacterial
      antigen in induced sputum from asthmatics.
AB  - The antigenic specificity and pathogenetic significance of immunoglobulins in
      airway secretion from asthmatic patients have not been established. Elevated
      levels of B-cells and immunoglobulin (Ig)A antibodies have been reported in
      sputum of asthmatics and these levels correlated with the eosinophil counts and
      levels of degranulated cytotoxic proteins from eosinophils. This study aimed to
      investigate the antigen specificity and possible pathogenetic significance of
      antibodies in airway secretion from asthmatic patients. Specific IgA and IgG
      antibodies to both allergen (Dermatophagoides farinae) and bacterial antigen
      (capsular polysaccharide antigen from Streptococcus pneumoniae) were measured in
      sputum from 16 atopic asthmatic patients sensitized to D. farinae and 12
      nonatopic, nonasthmatic controls by enzyme-linked immunosorbent assay. Sputum was
      induced by inhalation of hypertonic saline. Eosinophil cationic protein (ECP)
      levels in sputum from asthmatic patients were measured by the Pharmacia CAP
      system. Levels of IgA to both D. farinae and S. pneumoniae and IgG to D. farinae
      in the sputum from asthmatic patients were significantly higher than those from
      controls (p<0.005). No significant difference was found in the levels of IgG to
      S. pneumoniae between the two groups. In asthmatic patients, there were
      significant correlations between IgA to D. farinae and S. pneumoniae (r=0.76,
      p=0.003). Sputum ECP levels correlated significantly with IgA to D. farinae
      (r=0.55, p=0.03) and S. pneumoniae (r=0.56, p=0.03) and IgG to D. farinae
      (r=0.52, p=0.04), but not with IgG to S. pneumoniae in asthmatic patients. In
      conclusion, specific immunoglobulin A antibodies to both allergen and bacterial
      antigen were elevated in induced sputum from atopic asthmatics and their possible
      involvement in eosinophil degranulation was suggested.

PMID- 9762777
TI  - Increased peak expiratory flow variation in asthma: severe persistent increase
      but not nocturnal worsening of airway inflammation.
AB  - Asthma at night is characterized by a nocturnal increase in airway obstruction.
      It has been hypothesized that nocturnal asthma results from an increase in airway
      wall inflammation at night. However, studies on inflammatory cells in
      bronchoalveolar lavage (BAL) fluid and bronchial biopsies have produced
      conflicting data. This study assessed inflammatory cell numbers at 16:00 h and
      04:00 h in bronchial biopsies of 13 healthy controls, 15 asthmatic patients with
      peak expiratory flow (PEF) variation < or =15% and 10 asthmatic patients with PEF
      variation >15%. There was no significant increase at night in the number of CD3,
      CD4, CD8, CD25, AAI (tryptase) and EG2-immunopositive cells in the submucosa in
      both groups. Numbers of EG2-positive cells in the two asthmatic groups were
      significantly higher than in healthy controls, both at 16:00 h (p<0.05) and 04:00
      h (p<0.01). The number of EG2, CD4 and CD25-positive cells at 04:00 and 16:00 h
      tended to be higher in asthmatics with a PEF variation >15% than in asthmatics
      with PEF variation < or =15%. At 04:00 h the median numbers of EG2-positive cells
      (per mm basement membrane) in subjects with PEF variation >15% and < or =15% were
      6 and 3 cells, respectively, and at 16:00 h 4 and 25 cells respectively.
      Increased nocturnal airway obstruction is not associated with increased numbers
      of inflammatory cells in the bronchial submucosa at night. Apparently, asthmatic
      patients with a peak expiratory flow variation >15% suffer from a higher overall
      severity of bronchial inflammation at night and during the day.

PMID- 9762778
TI  - Sputum eosinophilia is more closely associated with airway responsiveness to
      bradykinin than methacholine in asthma.
AB  - Hyperresponsiveness of the airways to various spasmogenic stimuli is a
      characteristic feature of bronchial asthma. However, the association between the
      different stimuli to which asthmatic airways are hyperresponsive and airways
      inflammation is not completely understood. We have investigated the relationship
      between airway inflammation and airway hyperresponsiveness in asthma, as assessed
      by bronchoprovocation tests to methacholine and bradykinin, two well defined
      bronchoconstrictor agonists. Sputum induction by hypertonic saline and
      methacholine and bradykinin challenges were performed in 14 nonsmoking subjects
      with mild-to-moderate asthma. Airway responsiveness to either agonist did not
      correlate with sputum neutrophils, lymphocytes, and macrophages. Whilst the
      absolute number of eosinophilia failed to be significantly related to
      methacholine responsiveness (r=-0.47; p=0.09), it correlated markedly and
      significantly with provocative concentration of methacholine causing a 20% fall
      in forced expiratory volume in one second (r=0.72; p<0.01). When expressed as %
      of total cell counts, sputum eosinophils correlated with both types of
      responsiveness (r=-056; p=0.04 and r=-0.76, p<0.001, respectively). Although the
      concentration of eosinophil cationic protein (ECP) in the sputum correlated with
      the absolute numbers of eosinophils (r=0.62; p<0.02), no correlation was found
      between ECP levels and the airway responsiveness to any of the agonists tested.
      In subjects with mild-to-moderate asthma, airway responsiveness to bradykinin is
      more strongly associated with the magnitude of eosinophilic inflammation in the
      airways than methacholine. This finding underlines the selectivity of diverse
      agonists in assessing airway hyperresponsiveness and cellular inflammation in
      asthma.

PMID- 9762780
TI  - Characteristics of asthma in the elderly.
AB  - Asthma occurs more frequently in the elderly than is usually appreciated and may,
      therefore, be underdiagnosed and undertreated. This study evaluated the
      relationship between asthma symptoms and the degree of airflow obstruction in
      elderly and young asthmatics. Fifteen young asthmatics (<65 yrs) (group A), 15
      aged >65 yrs with onset of symptoms before 65 yrs (group B), and 15 aged >65 yrs
      with onset of symptoms after 65 yrs (group C), were studied. Patients used daily
      diary cards, during 2 weeks, to record inhaled beta2-agonist consumption and
      severity of asthma symptoms. Long-standing asthma was associated with a
      significantly lower forced expiratory volume in one second as compared with
      recent onset asthma. The asthma-symptom score was highest in group A, lower in
      group B and significantly lower in group C. When symptoms were related to the
      degree of obstruction (asthma index), it was higher in the young asthmatics than
      in both groups of elderly patients. In conclusion, elderly patients with long
      standing asthma had more severe airway obstruction than patients with recently
      acquired disease. Older patients particularly those with long-standing disease
      complained less about asthma symptoms. Within the various groups of patients,
      subjective symptoms of asthma were negatively related to asthma duration.

PMID- 9762779
TI  - Individual use of antiasthmatic drugs in the European Community Respiratory
      Health Survey.
AB  - A previous analysis of drug utilization in the European Community Respiratory
      Health Survey found that only between 8 and 29% of subjects with asthma-related
      symptoms were using antiasthmatic medication in the different areas studied. The
      aim of this analysis was to investigate which variables were related to
      individual use of antiasthmatic medication in different geographical areas.
      Thirty-three centres in 14 countries were analysed, in which a total of 16,854
      people (52.1% females, mean age 33.8 yrs, range 20-48) underwent a structured
      interview, measurement of specific immunoglobin E, spirometry and methacholine
      challenge test. The use of antiasthmatic drugs in individuals was, in most
      countries, independently related to asthma-related respiratory symptoms,
      bronchial hyperresponsiveness (BHR) and atopy. In all countries smokers with
      respiratory symptoms were less likely to be using antiasthmatic drugs than
      nonsmokers and exsmokers. In four of 14 countries females were significantly more
      likely to use antiasthmatic medication than males, while age and socioeconomic
      status were unrelated to medication. The use of inhaled anti-inflammatory drugs
      was positively related to symptoms, BHR and atopy and negatively related to
      current smoking. In conclusion, in many countries smokers were less likely to be
      using antiasthmatic drugs than were nonsmokers with comparable levels of symptoms
      and bronchial hyperresponsiveness. Age and socioeconomic status were unrelated to
      medication, while in some countries females were more likely than males to use
      antiasthmatic medication.

PMID- 9762781
TI  - Protective effect of respiratory devices in farmers with occupational asthma.
AB  - To the authors' knowledge there have been no previous reports on the protection
      afforded by powered filtering respirators in farmers with occupational asthma
      attributed to the inhalation of organic dust. In order to investigate this
      question, 26 farmers with occupational asthma were challenged with an exposure to
      work-related dusts for up to 60 min. This resulted in highly significant
      increases in airway resistance (Raw), thoracic gas volume (TGV) and specific
      airway resistance (sRaw) compared to baseline values. After a mean period of 21
      weeks the farmers were subjected to a second challenge, this time wearing a
      protective respiratory device (RD) with a P2 filter. Significant increases in
      Raw, TGV and sRaw were again observed, but on average these were 50-80% smaller
      than the increases seen when RDs were not worn. These differences were found to
      be statistically significant. This shows that the use of a respiratory device in
      farmers suffering from occupational asthma reduces the development of bronchial
      obstruction but does not prevent it. The use of this kind of respiratory device
      cannot substitute for the proper management of asthma since the devices do not
      offer complete protection.

PMID- 9762782
TI  - Tolerability to high doses of formoterol and terbutaline via Turbuhaler for 3
      days in stable asthmatic patients.
AB  - This randomized, double-blind, crossover study in two parts compared tolerability
      to high doses of formoterol (Oxis Turbuhaler) with that of high doses of
      terbutaline (Bricanyl Turbuhaler). After Holter monitoring at home, 12 patients
      were treated with 4+4+4 doses of formoterol Turbuhaler, 6 microg x dose(-1),
      (total daily metered dose 72 microg) or 4+4+4 doses of terbutaline Turbuhaler,
      0.5 mg x dose(-1) (daily dose 6 mg) given in the morning, after lunch and in the
      evening, for 3 consecutive days. After a one week washout period at home,
      patients received the alternative treatment. Thereafter, 15 other patients
      received 8+6+6 doses of formoterol Turbuhaler (total daily metered dose 120
      microg) or 8+6+6 doses of terbutaline Turbuhaler (daily dose 10 mg). Pulse,
      cardiac frequency, blood pressure, serum potassium, electrocardiogram and forced
      expiratory volume in one second (FEV1) were registered at regular intervals and
      Holter monitoring was applied during all 4 treatment days. Terbutaline 6 mg
      showed significantly greater systemic effects than formoterol 72 microg on pulse,
      blood pressure, cardiac frequency and QTc (QT interval corrected for heart rate).
      Terbutaline 10 mg had significantly greater effects than formoterol 120 microg on
      serum potassium levels, pulse, cardiac frequency and QTc. No differences in FEV1
      levels were found. Both drugs were safe and generally well tolerated on both dose
      levels. In conclusion, high doses of formoterol Turbuhaler over 3 days were
      generally safe and well tolerated. Daily doses of 6 mg and 10 mg terbutaline
      Turbuhaler were systemically more potent than 72 microg and 120 microg
      formoterol, respectively. The safety margin thus appears to be wide if patients
      happen to use extra doses of formoterol in addition to those prescribed for
      regular use.

PMID- 9762783
TI  - Subsensitivity to bronchoprotection against adenosine monophosphate challenge
      following regular once-daily formoterol.
AB  - Regular treatment with inhaled long-acting beta2-agonists leads to subsensitivity
      to their bronchoprotective effects, although the effect of dosing frequency on
      this subsensitivity is not known. The aim of this study was to assess whether a
      once-daily dosing regimen with formoterol might be associated with a lesser
      degree of subsensitivity. In a randomized placebo-controlled double-blind, double
      dummy crossover study 10 asthmatics treated with inhaled steroids (mean age 31
      yrs, forced expiratory volume in one second (FEV1) 82% predicted) received 1 week
      of treatment with: formoterol dry powder 24 microg twice daily (08:00 and 20:00
      h); formoterol 24 microg once daily (20:00 h); or identical placebo. Adenosine
      monophosphate (AMP) bronchial challenge was performed 12 h after the first and
      the last dose of each treatment. There was significant loss of protection with
      formoterol twice daily between the first and last dose (geometric mean
      provocative concentration causing a 20% fall in FEV1 (PC20)): 475 versus 129 mg x
      mL(-1) (a 3.7-fold loss, p=0.006) and with formoterol once daily: 367 versus 127
      mg x mL(-1) (a 2.9-fold loss, p=0.005), compared with placebo: 71 versus 75 mg x
      ml(-1) (nonsignificant). There was no significant difference in the degree of
      loss of protection between formoterol once and twice daily. For first-dose
      protection there was a significant difference between active treatments and
      placebo, but after the last dose the residual protection between active
      treatments and placebo was not significant. Thus, in patients taking inhaled
      corticosteroids, regular formoterol 24 micreog once daily induces a similar
      degree of subsensitivity to adenosine monophosphate bronchial challenge as with
      formoterol 24 microg twice daily. This in turn suggests that even with a 24-h
      dosing interval there is the development of tolerance to formoterol by prolonged
      occupancy of airway beta2-adrenoceptors.

PMID- 9762784
TI  - Effect of theophylline on CD11b and L-selectin expression and density of
      eosinophils and neutrophils in vitro.
AB  - The nonspecific phosphodiesterase inhibitor theophylline, widely used in asthma
      therapy, may cause a decrease in inflammatory responses of airways. In asthma,
      eosinophils migrate to the airway wall and become activated. Activated
      eosinophils are characterized by low cell density, as well as increased
      expression of CD11b and reduced expression of L-selectin, two adhesion molecules
      involved in transendothelial migration. To study the anti-inflammatory effect of
      theophylline on granulocyte adhesion molecules in vitro, the platelet-activating
      factor (PAF)-induced density shift was determined by density centrifugation and
      the modulation of CD11b and L-selectin expression by flow cytometry on
      eosinophils and neutrophils in human whole blood. A relatively high concentration
      of theophylline (10(-3) M) inhibited the increase in the percentage of hypodense
      eosinophils and neutrophils in whole-blood samples after PAF stimulation in
      vitro. A more pharmacological concentration (10(-4) M) inhibited the CD11b
      upregulation and L-selectin shedding induced by PAF (10(-7) M) on both
      eosinophils and neutrophils. The effect of isoproterenol on the inhibitory effect
      of theophylline was mainly additive, but a small synergistic effect could not be
      excluded. In conclusion theophylline can attenuate eosinophil and neutrophil
      activation in vitro at the level of adhesion molecule expression and changes in
      cell density. This may have implications for transendothelial migration of these
      cells in asthma.

PMID- 9762785
TI  - Four years' experience of intravenous colomycin in an adult cystic fibrosis unit.
AB  - Nearly all strains of Pseudomonas aeruginosa are sensitive to colomycin
      sulphomethate, but studies in the 1970s using large doses demonstrated
      significant renal and neurotoxic side-effects and it is not now commonly used. In
      this study colomycin (2 megaunits i.v. t.d.s.) has been used extensively in adult
      cystic fibrosis (CF) patients and its use reviewed to determine its efficacy and
      safety profile. Fifty-two CF patients (28 male, 24 female; mean age 26 yrs, range
      17-39 yrs) received 135 courses (mean two courses each, range 1-7, median length
      14 days) of i.v. colomycin (2,414 patient days in total). It was used in
      combination with one other i.v. antibiotic in 114 courses (85%) and with two
      others in 18 (13%). In all cases there was significant improvement in spirometry
      (pretreatment forced expiratory volume in one second (FEV1) % predicted mean
      44.4, range 10-101; post-treatment mean 51.3, range 14-108; p<0.0001). No patient
      had any neurotoxicity but one developed a skin rash and myositis. There was no
      change in renal function (urea mean pretreatment 4.1 mmol x L(-1) (sD 1.4), mean
      post-treatment 43 (2.2), p=NS; creatinine mean pretreatment 77.9 mmol x L(-1)
      (15.3), mean post-treatment 803 (21.6), p=NS). In the authors' experience
      intravenous colomycin sulphomethate in moderate doses is an effective and safe
      antipseudomonal antibiotic which is easy to administer. Other clinicians should
      consider its use in patients with cystic fibrosis.

PMID- 9762786
TI  - Leukocyte counts and macrophage phenotypes in induced sputum and bronchoalveolar
      lavage fluid from normal subjects.
AB  - It is unclear whether leukocytes in induced sputum (IS) and bronchoalveolar
      lavage (BAL) represent the same cell populations. To compare leukocyte counts and
      macrophage phenotypes and investigate any measurable dithiothreitol (DTT)
      mediated effect on macrophage immunocytochemical staining results, IS and BAL
      samples from nine healthy smokers and seven nonsmokers were examined. BAL and IS
      samples were processed and cell viability and cell counts were assessed. The
      macrophages were characterized by seven monoclonal antibodies (RFD1, RFD7, CD11b,
      CD54, CD68, CD71 and HLA-DR) using an indirect immunoalkaline phosphatase method.
      Intraindividual comparison of IS and BAL showed that IS samples from smokers and
      nonsmokers contained a lower total cell count (p<0.01 smokers, p<0.05
      nonsmokers), a lower percentage of macrophages (both p<0.05) and a higher
      percentage of neutrophils (both p<0.05) than BAL samples. In addition, nonsmokers
      sputum samples contained a lower proportion of lymphocytes (p<0.05) than BAL. The
      macrophage expression of RFD7 and CD71 was higher in smokers sputum samples (both
      p<0.05) than in BAL, while nonsmokers sputum macrophages showed a higher
      expression of CD54 and CD71 (both p<0.05) than BAL macrophages. DTT-incubated BAL
      samples showed no difference in macrophage antigen expression from BAL samples
      not exposed to DTT. In conclusion, the relative proportions of leukocytes and the
      macrophage phenotypes differed between induced sputum and bronchoalveolar lavage
      suggesting that the methods provide samples from different lung compartments,
      inhabited by cells with different phenotypes.

PMID- 9762787
TI  - Expression of leukocyte integrins and tissue factor in mononuclear phagocytes.
AB  - Coagulation is intimately involved in the pathology of inflammation. The
      leukocyte beta2-integrins have several functions, including serving as receptors
      for coagulation factor X and fibrinogen. Tissue factor (TF) is a receptor for
      factor VII and a very potent trigger of coagulation. The intention of this study
      was to examine a possible coexpression of beta2-integrins (CD11b/CD18 and
      CD11c/CD18) and the procoagulant TF in alveolar macrophages (AM) and blood
      monocytes, i.e. cells of the same differentiation lineage. The expression of
      beta2-integrins in human AM isolated by bronchoalveolar lavage and in blood
      monocytes was analysed by flow cytometry, whereas TF activity was analysed in a
      one-stage clotting assay. In monocytes, TF activity, CD11b and CD11c expression
      were highly inducible by lipopolysaccharide (LPS), with a 13-, 19- and four-fold
      increase, respectively. In AM, TF and beta2-integrins were all constitutively
      expressed, but the expression could not be further enhanced by LPS stimulation.
      CD11b and CD11c expression varied inversely with the cell size of AM, in contrast
      to TF activity which is known to be proportional to AM cell size. In vitro
      expression of beta2-integrins and tissue factor in lipopolysaccharide-stimulated
      blood monocytes seems to be intimately coregulated, whereas the expression of
      these receptors in alveolar macrophages seems to be unresponsive to
      lipopolysaccharide. These results indicate that blood monocytes and alveolar
      macrophages have different roles and use different mechanisms in cell-induced
      fibrin formation.

PMID- 9762788
TI  - Effects of alkaline protease or restrictocin deficient mutants of Aspergillus
      fumigatus on human polymorphonuclear leukocytes.
AB  - Several substances including proteases and restrictocin have been suggested as
      candidates for virulence determinants in invasive pulmonary aspergillosis.
      However, the roles of such substances are not well understood. This study
      compared the in vitro suppressive effects of Aspergillus fumigatus culture
      filtrates (ACFs), on the functions of human polymorphonuclear leukocytes (PMNLs),
      the principal cells in the host defence against aspergillus hyphae, from a
      clinically isolated wild-type and isogenic mutant strains which lack production
      of elastolytic alkaline protease (Alp) and/or restrictocin. ACFs were obtained by
      culturing conidia of each strain in Medium- 199 at 37 degrees C for 5 days. ACFs
      of the wild-type significantly (p<0.01) suppressed chemotaxis, superoxide anion
      (O2-) release and PMNL-mediated hyphal damage, compared with the control (Medium
      199). ACFs of the mutant strains that lack Alp or restrictocin significantly
      (p<0.01) suppressed chemotaxis and O2(-)-release, but did not suppress hyphal
      damage, compared with the control. The wild-type significantly (p<0.01)
      suppressed chemotaxis of PMNLs compared with the mutant strains lacking Alp or
      restrictocin, whereas there were no significant differences in suppression of O2(
      )-release and hyphal damage by PMNLs. ACF of a mutant strain that lacks both Alp
      and restrictocin had much less activity, but significantly (p<0.01) suppressed
      chemotaxis of PMNLs compared with the control. In conclusion, alkaline protease
      and restrictocin may play roles in the suppressive effect of Aspergillus
      fumigatus culture filtrates on the functions of human polymorphonuclear
      leukocytes. Other antiphagocytic substances produced by Aspergillus fumigatus
      remain to be identified.

PMID- 9762789
TI  - Neutrophils induce damage to respiratory epithelial cells infected with
      respiratory syncytial virus.
AB  - The mechanisms by which respiratory syncytial virus (RSV) infection induces
      bronchiolitis and airway disease are unclear. The presence of large numbers of
      polymorphonuclear leukocytes (PMN) in the airways of infants with RSV infection
      suggests a potential role of PMN in airway injury associated with RSV infection.
      To investigate the potential role of neutrophils in RSV bronchiolitis, human
      alveolar type II cells (A549 cells) were infected with different doses of RSV for
      6-48 h. A 51Cr-releasing assay was used to measure PMN-induced damage and image
      analysis was used to determine PMN adhesion and detachment of epithelial cells.
      The results showed that RSV infection of epithelial cells enhanced PMN adherence
      in a dose- and time-dependent pattern, RSV infection alone could damage and
      detach epithelial cells to a limited extent and PMN significantly augmented RSV
      infection-induced damage and detachment of epithelial cells. These data suggest
      that respiratory syncytial virus infection of respiratory epithelial cells
      enhances neutrophil adhesion to the epithelium and that activated neutrophils
      augment the damage and detachment of epithelium infected with the virus.
      Polymorphonuclear leukocytes may contribute to the pathogenesis of respiratory
      syncytial virus airway disease by inducing epithelial damage and cell loss.

PMID- 9762790
TI  - Th2 cytokines exert a dominant influence on epithelial cell expression of the
      major group human rhinovirus receptor, ICAM-1.
AB  - Intercellular adhesion molecule (ICAM)-1 is a cell receptor important in both
      human rhinovirus (HRV) attachment and immune effector cell mobilization. The
      level of expression of ICAM-1 by epithelial cells (EC) therefore plays a crucial
      role in the intricate biological phenomena underlying viral binding, host
      infection and consequent inflammatory events. As T-helper (Th)2 lymphocytes
      predominate within the asthmatic airway, the influence was evaluated of Th2
      associated mediators in the modulation of ICAM-1 expression on uninfected and HRV
      infected EC. H292 EC were cultured in vitro, with varying concentrations of
      interleukin (IL)-4, IL-5, IL-10 and IL-13 for 24 h and then infected with live
      HRV-14. Surface ICAM-1 expression was assessed by immunocytochemistry. Infection
      with HRV-14 resulted in a twofold increase in ICAM-1 expression. IL-4, IL-5, IL
      10 and IL-13 produced a 2.7-5.1-fold enhancement of ICAM-1 expression of
      uninfected cells and caused approximately a further twofold increase in infected
      cells over the expression induced by HRV infection itself. Interferon-gamma in
      combination with each Th2-associated cytokine only slightly reduced, but did not
      override, the Th2-induced level of ICAM-1 expression on both uninfected and virus
      infected EC. These data suggest that the effects of Th2-associated cytokines on
      intercellular adhesion molecule-1 expression and recovery of infectious virus are
      dominant over the effects of the Th1-associated cytokines such as interferon
      gamma. Since the airway mucosa in atopic asthma is predominantly infiltrated by
      Th2 lymphocytes, these results could explain both the increased susceptibility to
      human rhinovirus infection in asthmatic patients and the associated exacerbation
      of asthma symptoms.

PMID- 9762791
TI  - Tracking of lung function parameters and the longitudinal relationship with
      lifestyle.
AB  - The purpose of this study was to analyse tracking (i.e. relative stability over
      time/predictability of future values by early measurements) of lung function
      parameters and their longitudinal relationship with lifestyle (smoking, alcohol
      consumption, daily physical activity, neuromotor and cardiopulmonary fitness, and
      dietary intake of retinol and polyunsaturated fatty acids (PUFA)). Data were
      obtained from the observational Amsterdam Growth and Health Study, a longitudinal
      study with six repeated measurements between ages 13-27 yrs (n=167). The
      statistical analyses were carried out with generalized estimating equations. The
      following "stability" coefficients were found: for forced vital capacity (FVC) in
      males 0.66 (95% confidence interval (CI): 0.54-0.77) and in females 0.51 (95% CI:
      0.43-0.60); for forced expiratory volume in one second (FEV1) in males 0.65 (95%
      CI: 0.50-0.80), in females 0.53 (95% CI 0.46-0.60); for peak expiratory flow
      (PEF) in both males and females 0.41 (95% CI: 0.31-0.51). Positive relationships
      were found between alcohol consumption and FVC and FEV1 and between neuromotor
      fitness and PEF and (only for males) with FVC and FEV1. Physical activity was
      inversely related to PEF and the intake of PUFA positively related to FVC and
      FEV1. Smoking was related to a decrease in FVC and FEV1; changes in physical
      activity positively correlated to changes in FVC. In conclusion, high to moderate
      stability/tracking was observed for forced vital capacity and forced expiratory
      volume in one second; for peak expiratory flow it was slightly lower. Preventive
      strategies regarding improvements of lung function should focus on smoking
      cessation and improving daily physical activity.

PMID- 9762792
TI  - Impaired ventilatory function and elevated insulin levels in nondiabetic males:
      the Normative Aging Study.
AB  - Lower levels of baseline ventilatory function have consistently been associated
      with increased risk of cardiovascular mortality in prospective studies, but the
      underlying mechanisms are not known. Increased risk of coronary heart disease is
      associated with higher serum insulin levels. This report examines the
      relationship between ventilatory function and indirect measures of insulin
      resistance. Cross-sectional data from 922 nondiabetic participants in the
      Normative Aging Study were analysed using multiple linear regression models with
      adjustment for potential confounders. Forced vital capacity (FVC) and forced
      expiratory volume in one second (FEV1) were examined in relation to indicators of
      insulin resistance, i.e. fasting insulin and the fasting insulin resistance index
      (FIRI). Diabetics were excluded because impaired insulin secretion interferes
      with the validity of these as measures of insulin resistance. Fasting insulin and
      FIRI were negatively correlated with FVC and FEV1 (all p< 0.001). These
      associations persisted after adjusting for potential confounders including age,
      height, body mass index, waist to hip circumference ratio, physical activity,
      alcohol intake and smoking in separate multiple linear regression models, for
      both insulin (all p< or =0.0008) and FIRI (all p< or =0.0001). Negative cross
      sectional associations between ventilatory function and indirect measures of
      insulin resistance were found in nondiabetic males. Insulin resistance may
      contribute to the previously unexplained association between ventilatory function
      impairment and cardiovascular mortality. Mechanisms underlying the relationship
      between insulin resistance and decreased ventilatory function remain to be
      elucidated.

PMID- 9762793
TI  - Baseline ventilatory function predicts the development of higher levels of
      fasting insulin and fasting insulin resistance index: the Normative Aging Study.
AB  - A consistent but as yet unexplained association between baseline ventilatory
      function and risk of coronary heart disease (CHD) has been reported from many
      prospective studies. Insulin-resistant states are associated with increased risk
      of CHD. Forced vital capacity (FVC), forced expiratory volume in one second
      (FEV1) and maximal mid-expiratory flow rate (MMEF) at study entry were examined
      as predictors for indirect measures of insulin resistance after a mean follow-up
      interval of 20.9 yrs in 1050 nondiabetic male subjects in the Normative Aging
      Study. Males in the top quintile of insulin or fasting insulin resistance index
      (FIRI) levels at follow-up were defined as being relatively insulin resistant.
      FVC was negatively associated with risk of being relatively insulin resistant
      using the insulin (p=0.002) or FIRI (p=0.0001) criteria at follow-up in logistic
      regression models adjusting for baseline age, body mass index, fat distribution
      pattern and cigarette smoking. Similar associations were found for FEV1 and MMEF.
      Additional adjustment for baseline postcarbohydrate challenge glucose levels made
      little difference to the results, suggesting that baseline glucose intolerance
      was not a significant source of bias. These findings are consistent with the
      possibility that insulin resistance may be one of the factors mediating the
      previously unexplained prospective association between impairment of ventilatory
      function and risk of mortality from coronary heart disease.

PMID- 9762794
TI  - Time to peak tidal expiratory flow and the neuromuscular control of expiration.
AB  - The ratio of the time needed to reach peak tidal expiratory flow (tPTEF) and the
      duration of expiration (tE) is used to detect airflow obstruction in young
      children. tPTEF is decreased in patients with asthma, but knowledge about the
      physiological determinants of this parameter is scarce. This study examined the
      relationship between tPTEF and postinspiratory activities of inspiratory muscles
      and evaluated the effects of changing sensory information from the lung. Airflow
      patterns and electromyographic (EMG) activity of inspiratory muscles were
      recorded in seven spontaneously breathing, anaesthetized cats. The trachea was
      cannulated and, as a result, the larynx and upper airways were bypassed. Changes
      in postinspiratory muscle activity were induced by changing afferent sensory
      nerve information (by cooling the vagus nerves, by administration of histamine
      and by additional application of continuous positive airway pressure (CPAP)).
      Durations of postinspiratory activities of the diaphragm and intercostal muscles
      (characterized by their time constants tau diaphr and tau interc) correlated
      strongly with tPTEF (r=0.85 and 0.77, respectively). Tau diaphr, tau interc and
      tPTEF were significantly increased during cooling of the vagus nerves (4-8
      degrees C) compared with values at 22 and 37 degrees C (p<0.05). Conversely,
      administration of histamine and CPAP caused significant decreases in tau diaphr,
      tau interc and tPTEF, which were absent during cooling of the vagus nerves. In
      conclusion, the time needed to reach peak tidal expiratory flow is highly
      influenced by the activities of inspiratory muscles during the early phase of
      expiration which, in turn, depend on the activities of vagal receptors in the
      lung.

PMID- 9762795
TI  - Acute effects of hypoxaemia, hyperoxaemia and hypercapnia on renal blood flow in
      normal and renal transplant subjects.
AB  - The aim of this investigation was to study noninvasively the effects of
      hypoxaemia, hyperoxaemia and hypercapnia on renal blood flow in normal subjects
      and renal allograft recipients, i.e. with denervated kidneys. By comparing these
      two groups, the influence of renal innervation on any resulting changes in renal
      blood flow could be ascertained. Nine normal and eight renal allograft recipients
      were studied. Each subject inhaled the following gas mixtures in order: room air,
      10% O2 (hypoxaemia), 10% O2 + baseline CO2 (isocapnic hypoxaemia), 10% O2 + high
      CO2 (hypercapnic hypoxaemia), 100% O2 (hyperoxaemia), 100% O2 + baseline CO2
      (isocapnic hyperoxaemia) and 100% O2 + high CO2 (hypercapnia hyperoxaemia). Using
      Doppler ultrasonography, the pulsatility index (PI), an index of renovascular
      resistance, was measured at the various gas inhalation levels. In normal
      subjects, the renovascular resistance increased in response to hypoxaemia, with a
      greater increase in response to hypercapnic hypoxaemia. Hyperoxaemia caused a
      decrease in renovascular resistance but this was abolished with the addition of
      CO2. There was a similar pattern in the PI response to the different gas
      inhalations in the renal transplant subjects, but these responses were attenuated
      in comparison with those of the normals. In conclusion, renal denervation does
      not completely abolish the renovascular responses to inhaled oxygen and carbon
      dioxide.

PMID- 9762796
TI  - In vivo hypoxic exposure impairs metabolic adaptations to a 48 hour fast in rats.
AB  - Hypoxia is well known to affect carbohydrate metabolism through its action on
      liver function and thus on glucose homeostasis. The aim of this study was to
      examine the carbohydrate, lipid and protein metabolic responses to 48 h of
      hypoxia, as well as the hormonal adaptations using both normoxic controls and
      hypoxic animals in the fasted state to standardize for the marked hypophagia
      observed in response to hypoxia. Hypoxia exposure (inspiratory oxygen fraction
      (FI,O2) = 0.1) resulted in a greater weight loss (-23 +/- 3.6% versus -16 +/- 2%
      in controls, p<0.001). Hypoxia plus fasting led to a significant increase in
      plasma glucose, lactate, insulin and catecholamine concentrations, while the
      increase in free fatty acid and beta-hydroxybutyrate was abolished. Changes in
      plasma amino acid patterns were not affected by hypoxia. Liver glycogen depletion
      was significantly less pronounced in the hypoxic group, while phosphoenolpyruvate
      carboxykinase (a key enzyme of liver gluconeogenesis) activity and transcription
      enhancements were abolished by hypoxia. Overall, hypoxic exposure in rats fasted
      for 48 h resulted in a unique pattern that differed from responses to injury or
      fasting per se. Oxygen seems to play a central role in the metabolic adaptation
      to fasting, from gene expression to weight loss. Since hypoxaemia associated with
      fasting has detrimental effects on nutritional balance, the present observations
      may be clinically relevant in the setting of acute exacerbation with hypoxaemia
      for chronic respiratory disease.

PMID- 9762797
TI  - Mouth occlusion pressure, CO2 response and hypercapnia in severe chronic
      obstructive pulmonary disease.
AB  - The resting mouth occlusion pressure 0.1 s after onset of inspiration (P0.1) and
      minute ventilation (V'E) and their response to CO2 in patients with chronic
      obstructive pulmonary disease (COPD) remain controversial. The ventilatory drive
      and the factors that predict resting arterial CO2 tension (Pa,CO2) were studied
      in 19 eucapnic and 14 hypercapnic severe COPD patients, and 20 controls. The CO2
      response was evaluated by the Read technique. The V'E, and P0.1 as a function of
      end-tidal CO2 tension (Pet,CO2) was used to study the ventilatory
      (deltaV'E/deltaPet,CO2) and P0.1 response (deltaP0.1/deltaPet,CO2). In the
      patients, respiratory muscle function and pleural occlusion pressure 0.1 s after
      onset of inspiration (Ppl,0.1) were evaluated with simultaneous measurement of
      pleural (Ppl) and gastric (Pga) pressures. Hypercapnic patients had lower forced
      vital capacity (FVC), forced expiratory volume in one second (FEV1), and arterial
      O2 tension (Pa,O2). Resting P0.1 was higher in patients than in controls, whereas
      deltaP0.1/deltaPet,CO2 was similar in the three groups. There was no difference
      in resting P0.1 (3.6+/-2.0 versus 4.3+/-2.8 kPa (2.7+/-1.5 versus 3.2+/-2.1
      cmH2O), p=0.2) and Ppl,0.1 (1.4+/-2.3 versus 5.2+/-3.3 kPa (4.08+/-1.7 versus
      3.9+/-2.5 cmH2O), p=0.22) between eucapnic and hypercapnic COPD, whereas
      deltaV'E/deltaPet,CO2 was lower in the hypercapnic group (0.29+/-0.24 versus
      0.66+/-0.5 L x min(-1) x kPa, p<0.001). By logistic regression only FEVI and
      increased diaphragmatic load, and not respiratory drive, predicted resting
      Pa,CO2. Irrespective of CO2 level, baseline central drive (represented by the
      mouth occlusion and pleural pressures) and CO2 response are preserved in most
      patients with severe chronic obstructive pulmonary disease. Effective ventilation
      is inadequate in the more severely obstructed patients and this results in
      hypercapnia. Neuroventilatory coupling failure is an attractive explanation for
      chronic hypercapnia in these patients.

PMID- 9762798
TI  - Use of mouth pressure twitches induced by cervical magnetic stimulation to assess
      voluntary activation of the diaphragm.
AB  - There is a need for a simple method to assess the adequacy of diaphragm
      activation during voluntary inspiratory efforts in patients with suspected
      respiratory muscle weakness. We have compared mouth (Pmo,t), oesophageal (Poes,t)
      and transdiaphragmatic (Pdi,t) twitch pressure elicited by cervical magnetic
      stimulation (CMS) in five normal men (mean (SD) age 32.2 (1.8) yrs) on two
      separate study days. Single magnetic stimuli were delivered at functional
      residual capacity during relaxation and during graded voluntary inspiratory
      efforts against a closed airway. As voluntary-effort transdiaphragmatic and
      oesophageal pressure increased, Pdi,t and Poes,t decreased linearly (r range,
      respectively, 0.82-0.98 and 0.87-0.95). During relaxation, Pmo,t was unreliable
      due to the poor transmission of intrathoracic pressure, but during inspiratory
      efforts, the relation between voluntary mouth pressure and Pmo,t was also linear
      (r range 0.84-0.95). On average, our subjects voluntarily generated 99, 100 and
      102% of the maximum transdiaphragmatic, oesophageal and mouth pressures predicted
      by the respective linear regression equations. Pmo,t was correlated to both
      Poes,t and Pdi,t during inspiratory efforts, but not during relaxation. These
      studies confirm that twitch pressures induced by CMS during inspiratory efforts
      can be assessed at the mouth in normal subjects, providing a simple and non
      invasive technique for assessing diaphragm activation during voluntary
      inspiratory efforts. Potentially, this technique could be made more sensitive and
      accurate and applied to detect submaximal efforts in patients.

PMID- 9762799
TI  - Pulmonary haemodynamics in obstructive sleep apnoea: time course and associated
      factors.
AB  - Changes in pulmonary artery pressure within an obstructive apnoea and elevations
      of transmural pulmonary artery pressure (Ppa,tm) towards the end of apnoea are
      well known. The purpose of our study was to examine which factors contribute to
      the increase of Ppa,tm in an apnoea. In addition, the time course of Ppa,tm and
      associated factors during a sleep study was investigated. We analysed the
      association of changes in arterial oxygen saturation (Sa,O2), oesophageal
      pressure (Poes) to estimate intrathoracic pressure, systolic blood pressure
      (BPsys) to estimate left ventricular afterload, apnoea duration and the change in
      Ppa,tm (deltaPpa,tm) during the course of obstructive apnoeas. Consecutive
      apnoeas in nonrapid eye movement (NREM)-sleep at the beginning, the middle and
      the end of the sleep study were analysed in six patients with obstructive sleep
      apnoea. The mean systolic Ppa,tm was 28.0+/-12.1 mmHg at the beginning of apnoea
      and 38.6+/-15.5 mmHg at the end (deltaPpa,tm 10.5+/-7.4 mmHg; p<0.0001).
      DeltaSa,O2 (p<0.0001; odds ratio (OR) 1.45; confidence interval (CI) 1.20-1.76)
      and deltaPoes (p<0.0001; OR 1.22; CI 1.11-1.34) were independently associated
      with deltaPpa,tm in a multiple regression analysis. Apnoea duration as well as
      deltaPoes, deltaPpa,tm and deltaSa,O2 were all significantly higher (p<0.05) in
      apnoeas at the middle of the sleep study than at the beginning or the end. In
      conclusion, hypoxaemia and mechanical factors as an increase in negative thoracic
      pressure contribute to elevations of the transmural pulmonary artery pressure
      during an obstructive apnoea. The time course of pulmonary haemodynamics within a
      steep study reveals that the highest transmural pulmonary artery pressure occurs
      in the middle of the night with no progressive increase towards the end of the
      sleep study.

PMID- 9762800
TI  - Value of beat-to-beat blood pressure changes, detected by pulse transit time, in
      the management of the obstructive sleep apnoea/hypopnoea syndrome.
AB  - Two important aspects of a respiratory sleep study are a measure of inspiratory
      effort and an estimate of the number of arousals. These can be derived from an
      indirect estimate of beat-to-beat blood pressure (BP), pulse transit time (PTT).
      This study investigated the reproducibility of inspiratory BP falls (reflecting
      inspiratory effort), and BP arousals derived from PTT, and the contribution they
      could make to the management of the obstructive sleep apnoea/hypopnoea syndrome
      (OSAHS). Overnight PTT was recorded at home in 40 patients being investigated for
      OSAHS, and a second PTT recording was made in the sleep laboratory with full
      polysomnography. Patients were divided into three groups according to the
      severity of their sleep disorder, and a third PTT recording was made at home in
      13 patients subsequently established on nasal continuous positive airway pressure
      (CPAP). The reproducibility between the home and laboratory studies was
      reasonable (r=0.87 for inspiratory BP falls, r=0.81 for BP arousals). Both
      derivatives showed a clear progression through the three patient groups, which
      returned to normal on treatment. The differences between the groups were
      significant (p<0.001 for inspiratory BP falls, p=0.0014 for BP arousals).
      Receiver operator characteristic curves, used to compare polysomnography
      variables and PTT variables, confirmed that the PTT variables were as good as
      apnoea-hypopnoea index (AHI), >4% arterial oxygen saturation dip rate and
      electroencephalography micro-arousals at dividing patients into two groups,
      either requiring nasal CPAP or not requiring CPAP. Pulse transit time can provide
      a noninvasive estimate of inspiratory effort and a measure of arousals that
      together document disease severity and response to treatment and may be useful in
      managing obstructive sleep apnoea/hypopnoea syndrome.

PMID- 9762801
TI  - Maximum rate of change in oesophageal pressure assessed from unoccluded breaths:
      an option where mouth occlusion pressure is impractical.
AB  - The mouth occlusion pressure 100 ms after onset of inspiration (P0.1) is
      considered a clinically useful measure of the combined output of the respiratory
      centre and muscle pump. However, theoretical and practical difficulties can arise
      when using P0.1 in the assessment of patients with severe chronic obstructive
      pulmonary disease (COPD). It was hypothesized that the maximum rate of change in
      oesophageal pressure (dPoes,max/dt) may be an alternative to P0.1. To test this
      hypothesis P0.1 was compared with mean dPoes,max/dt measured from neighbouring
      unoccluded breaths in five normal subjects during CO2 rebreathing. In all
      subjects a close correlation was found between both dPoes,max/dt and P0.1 and
      carbon dioxide tension (PCO2). In six patients with severe COPD performing
      exhaustive treadmill walks, dPoes,max/dt was found to increase progressively with
      walking time. Mean dPoes,max/dt at the start was 6.2 cmH2O x 100 ms(-1) and at
      the finish was 18.7 cmH2O x 100 ms(-1) (p<0.03). In conclusion, the maximum rate
      of change in oesophageal pressure measured from unoccluded breaths could be an
      alternative in circumstances where it is not feasible to use measurements of the
      mouth occlusion pressure 100 ms after onset of inspiration.

PMID- 9762802
TI  - A simple breathing circuit minimizing changes in alveolar ventilation during
      hyperpnoea.
AB  - Many clinical and research situations require maintenance of isocapnia, which
      occurs when alveolar ventilation (V'A) is matched to CO2 production. A simple,
      passive circuit that minimizes changes in V'A during hyperpnoea was devised. It
      is comprised of a manifold, with two gas inlets, attached to the intake port of a
      nonrebreathing circuit or ventilator. The first inlet receives a flow of fresh
      gas (CO2=0%) equal to the subject's minute ventilation (V'E). During hyperpnoea,
      the balance of V'E is drawn (inlet 2) from a reservoir containing gas, the carbon
      dioxide tension (PCO2) approximates that of mixed venous blood and therefore
      contributes minimally to V'A. Nine normal subjects breathed through the circuit
      for 4 min at 15-31 times resting levels. End-tidal PCO2 (Pet,CO2) at rest, 0, 1.5
      and 3.0 min were (mean+/-SE) 5.1+/-0.1 kPa (38.1+/-1.1 mmHg), 4.9+/-0.1 kPa
      (36.4+/-1.1 mmHg), 5.0+/-0.2 kPa (37.8+/-1.6 mmHg) and 5.0+/-0.2 kPa (37.6+/-1.4
      mmHg) (p=0.53, analysis of variance (ANOVA)), respectively; without the circuit,
      Pet,CO2 would be expected to have decreased by at least 2.7 kPa (20 mmHg). Six
      anaesthetized, intubated dogs were first ventilated at control levels and then
      hyperventilated by stepwise increases in either respiratory frequency (fR) from
      10 to 24 min(-1) or tidal volume (VT) from 400 to 1,200 mL. Increases in fR did
      not significantly affect arterial CO2 tension (Pa,CO2) (p=0.28, ANOVA). Only the
      highest VT decreased Pa,CO2 from control (-0.5 +/- 0.3 kPa (-3.4 +/- 2.3 mmHg),
      p<0.05). In conclusion, this circuit effectively minimizes changes in alveolar
      ventilation and therefore arterial carbon dioxide tension during hyperpnoea.

PMID- 9762803
TI  - Respiratory bronchiolitis in smokers with spontaneous pneumothorax.
AB  - Respiratory bronchiolitis (RB) is defined by the accumulation of pigmented
      macrophages in the lumen and wall of respiratory and membranous bronchioles of
      smokers. The aim of this study was to determine whether spontaneous pneumothorax
      was associated with a high prevalence of RB. Seventy-nine consecutive patients
      who underwent a surgical procedure (thoracotomy or thoracoscopy) for recurrence
      or persistence of primary spontaneous pneumothorax despite thoracic drainage were
      studied retrospectively. RB was found in 70 of 79 (88.6%) smokers operated for
      spontaneous pneumothorax. Associated interstitial pathological abnormalities were
      present in 53 of 79 cases (67.1%). In nine patients, the pathological lesions
      were severe and resembled desquamative interstitial pneumonia. Emphysematous
      lesions were present in about one-third of the patients. Although the possible
      pathophysiological consequences of respiratory bronchiolitis remain speculative,
      this study demonstrates the high prevalence of this pathological abnormality in
      patients with pneumothorax requiring surgical treatment.

PMID- 9762804
TI  - Many faces of pulmonary aspergillosis.
AB  - Aspergillus is a ubiquitous fungus. It is commonly isolated as an upper
      respiratory tract saprophyte and is the most frequent contaminant in laboratory
      specimens. Because species of aspergillus are omnipresent, one must be cautious
      in ascribing a causal role to the fungus obtained from patients. Aspergillus has
      low pathogenicity for humans and animals and rarely invades the immunologically
      competent host. Although the fungus can affect any organ system, the respiratory
      tract is involved in >90% of afflicted patients. Pulmonary aspergillosis,
      depending whether the host is atopic or immunosuppressed, may be classified under
      four categories: allergic or hypersensitivity syndromes, saprophytic
      colonization, invasive (infective) dissemination, and chemical or toxic
      pneumonitis. These entities differ clinically, radiologically, immunologically,
      and in their response to various therapeutic agents. An increased awareness, an
      aggressive approach to securing the diagnosis, and instituting early and
      appropriate therapy are needed to reduce the high morbidity and mortality caused
      by many of the aspergillus-related syndromes.

PMID- 9762806
TI  - Deep breathing and awake apnoea in a patient who had recurrent hypoxaemia and
      hypercapnia without sleep apnoea.
AB  - A 21 yr old with deep breathing and awake apnoea, who had recurrent hypoxaemia
      and hypercapnia without sleep apnoea, was presented. Although the organic
      abnormality responsible for the breathing disturbance was not found,
      administration of acetazolamide facilitated several breaths between sighs, and
      the patient's hypoxaemia with hypercapnia improved. Some patients who have
      abnormalities in the cortical control of breathing that cannot be detected by
      present methods of examination may experience some improvement in breathing with
      the administration of chemical stimulants such as acetazolamide.

PMID- 9762805
TI  - Sarcoidosis: immunopathogenetic concepts and their clinical application.
AB  - Our understanding of the immunopathogenesis of sarcoidosis has been advanced by
      studies of bronchoalveolar lavage cells. Activated macrophages and T-cells have
      been identified in different compartments of the sarcoid lung and the
      characteristics of the activation suggest that the cells become activated in the
      course of a normal immune response. The immune cells communicate via a cytokine
      network and the measuring of cytokine levels yields subgroups of sarcoidosis
      patients with different courses of the disease indicating different states of
      activation of the disease-mediating immune cells. The causative agent of
      sarcoidosis has not yet been identified; however, some of the described
      mechanisms can be clinically applied either to detect patients at risk of
      deterioration or to develop new therapeutic strategies. Using these approaches
      methotrexate, pentoxifylline and thalidomide have been identified as drugs which
      effectively suppress sarcoid inflammation and the serum level of soluble
      interleukin-2 receptors has been delineated to be a serum marker of sarcoid
      inflammation. Furthermore, analysing the pulmonary cytokine network in
      sarcoidosis will yield new staging parameters possibly supplying prognostic
      information and guiding therapeutic intervention.

PMID- 9762807
TI  - A case of respiratory muscle weakness due to cytochrome c oxidase enzyme
      deficiency.
AB  - Mitochondrial myopathy is a rare cause of dyspnoea and respiratory failure,
      usually presenting in infancy. We describe a 27 yr old woman with a partial
      cytochrome c oxidase enzyme deficiency causing respiratory muscle weakness and
      respiratory failure. The onset was acute, with no preceding respiratory symptoms.
      The patient was successfully treated with bilevel positive airway pressure
      therapy.

PMID- 9762808
TI  - Polypoid bronchial lesions due to Scedosporium apiospermum in a patient with
      Mycobacterium avium complex pulmonary disease.
AB  - A 69 yr old female was hospitalized for further examination of abnormal shadows
      on chest radiographs. She had a history of tuberculous pleurisy, rheumatoid
      arthritis and gold-induced interstitial pneumonia. On admission she still
      suffered from rheumatoid arthritis. A chest computed tomography scan on admission
      showed clusters of small nodules in subpleural regions of both lungs combined
      with bronchiectasis. Mycobacterium avium complex was cultured repeatedly from the
      sputum. Bronchoscopic examination disclosed white-yellow polypoid lesions in the
      orifice of the left B4 bronchus. Cultures of the brushing specimen of the
      polypoid lesions and bronchial aspirates from the B4 bronchus yielded smoky-grey
      mycelial colonies that were later identified as Scedosporium apiospermum. It was
      concluded that the polypoid bronchial lesions due to Scedosporium apiospermum
      were formed in the preexisting dilated bronchus caused by Mycobacterium avium
      complex pulmonary disease.

PMID- 9762809
TI  - Half-night polysomnography: how is it compared to full-night polysomnography?

PMID- 9762810
TI  - Sarcoid granulomatosis after zirconium exposure with multiple organ involvement.

PMID- 9762811
TI  - Dermatology resources on the internet: a practical guide for dermatologists.

PMID- 9762812
TI  - Tinea versicolor.

PMID- 9762813
TI  - The prognosis of patients with basal and squamous cell carcinoma of the skin.

PMID- 9762814
TI  - Amyopathic dermatomyositis in Hong Kong -- association with nasopharyngeal
      carcinoma.
AB  - BACKGROUND: Amyopathic dermatomyositis (ADM) is a rare variant of dermatomyositis
      (DM) in which there is no apparent muscle involvement at initial presentation,
      but clinical and laboratory evidence of myopathy may appear later. Like DM, it
      has a known association with malignancy. OBJECTIVE: To record the occurrence of
      ADM in Hong Kong during the period from January 1988 to June 1996, and to
      establish the types of carcinoma with which it is associated. METHODS: The
      records of all patients diagnosed with ADM in three major dermatology clinics in
      Hong Kong were retrospectively studied to confirm the diagnosis and to look for
      any associated malignancy at any stage of the disease. RESULTS: Between 1988 and
      1996, six patients in Hong Kong (five men and one woman; mean age, 50 years)
      fulfilled the criteria of ADM. During a follow-up period ranging from 20 to 90
      months (average, 35.6 months), none developed any evidence of myositis.
      Associated malignancy was found in the five male patients. There were three cases
      of nasopharyngeal carcinoma (NPC), one case of non-small cell carcinoma of the
      lung, and one case of metastatic carcinoma of the cervical lymph node of unknown
      primary. No carcinoma had developed in the female patient during a follow-up
      period of 90 months. CONCLUSIONS: There is a strong association between ADM and
      NPC in Hong Kong.

PMID- 9762815
TI  - Relapsing cutaneous polyarteritis nodosa associated with streptococcal
      infections.
AB  - BACKGROUND: Polyarteritis nodosa is an aggressive, often fatal form of vasculitis
      associated with multi-organ involvement. Cutaneous polyarteritis nodosa is
      purported to be a more benign form of this disorder with involvement limited to
      the skin. METHODS: The identification of a female patient from childhood to
      adulthood documenting repeated episodes of cutaneous polyarteritis nodosa
      following bouts of recurrent streptococcal pharyngitis. RESULTS: Repeated bouts
      of streptococcal pharyngitis at ages 11, 28, and 33 years were followed by
      episodes of cutaneous polyarteritis nodosa, documented by histopathologic skin
      changes and clinical presentation, and confirmed by therapeutic management.
      CONCLUSIONS: Various infectious and non-infectious conditions have been linked
      both to the initiation and relapse of this disease. We describe a patient with
      recurrent episodes of cutaneous polyarteritis nodosa spanning a period of over 20
      years with each episode appearing to be linked to a prior streptococcal
      infection.

PMID- 9762816
TI  - Erythema nodosum and associated diseases. A study of 129 cases.
AB  - BACKGROUND: Erythema nodosum (EN) is associated with many infectious diseases.
      The purpose of this study was to evaluate the relative prevalence of associated
      diseases in a large series of EN, and to review the previously described causes
      of EN. MATERIALS AND METHODS: A total of 157 inpatients with a diagnosis of EN
      made in Strasbourg, France between 1960 and 1995 were studied retrospectively,
      but only 129 patients with confirmed EN were evaluated. A biopsy was taken in 30
      patients with atypical clinical symptoms. Chest radiography, blood cell count,
      throat swab, and anti-streptolysin dosage were performed systematically. Viral
      investigations and serodiagnoses for various bacterial infections were carried
      out in approximately half of the patients. All investigations were analyzed
      retrospectively and compared with the world literature. RESULTS: The female: male
      ratio was 5 : 1 and the mean age was 31 years. We found 28% confirmed
      streptococcal infections, 11% sarcoidosis, 1.5% enteropathies, 1.5% Chlamydia
      infections, 0.8% Mycoplasma infections, 0.8% Yersinia infections, 0.8% hepatitis
      B, and 0.8% tuberculosis (one case). The causative factor could not be determined
      in 55% of patients. CONCLUSIONS: Our data confirm the predominance of
      streptococcal infections and sarcoidosis among patients with EN. Tuberculosis has
      virtually disappeared, since the last case was observed in 1962. Various viral or
      bacterial diseases are rarely associated with EN, but all patients were not
      thoroughly investigated. A large and prospective study should be performed in
      order to determine the true prevalence of associated diseases in EN. In the
      absence of specific symptoms, exhaustive investigations are not cost-effective.

PMID- 9762817
TI  - Skin diseases in Bamako (Mali).
AB  - BACKGROUND: Skin diseases have only recently been considered as a possible public
      health problem in developing countries. Data supporting this matter are scarce.
      The aim of this study is to report the experience of a specialized dermatologic
      center in Bamako (Mali) in order to complete two previous studies conducted in
      the Bamako area: a prevalence study in the general population and a study in
      nonspecialized health centers of Bamako. It is our intention to provide a
      comprehensive picture of the problem of skin diseases in an African developing
      country. METHODS: We retrospectively collected all cases of skin diseases
      diagnosed during consultations provided at the Institut Marchoux in Bamako, the
      only center specializing in dermatology in Mali, during the year 1993. RESULTS: A
      total of 10,575 new outpatients were seen with 10,889 skin diseases. The main
      skin diseases registered were as follows: infectious dermatoses (41% of all
      diagnoses, including scabies (16.6%), superficial mycoses (13.6%), and primary
      pyoderma (5.6%)), dermatitis (20.4%), papular urticaria (4.4%), acne (4.2%),
      pityriasis alba (3.6%), keratoderma (3.6%), and urticaria (3%). Typical tropical
      infectious diseases accounted for only 1% of all diagnoses. CONCLUSIONS: It
      appears that certain skin diseases (mainly scabies and pyoderma) are an important
      health problem for the population of the Bamako area. Public health policies
      should be implemented in order to manage this problem rationally.

PMID- 9762818
TI  - Frequency of pre-existing actinic keratosis in cutaneous squamous cell carcinoma.
AB  - BACKGROUND: Controversy over the rate of malignant transformation of actinic
      keratosis (AK) into cutaneous squamous cell carcinoma (SCC) has generated
      considerable debate regarding the importance of treating all such precancers to
      preclude their transofrmation. Current changes in US healthcare policy will deny
      many individuals access to certain simple and effective treatment modalities for
      precancerous lesions. OBJECTIVE: Our purpose was to determine whether there is a
      significant association between the presence of cutaneous SCC and pre-existing
      AK. METHODS: One hundred and sixty five consecutive cases of cutaneous SCC,
      retrieved from the files of a university-affiliated dermatopathology laboratory
      serving north-central Florida, were selected for review by a single
      dermatopathologist (D.M.). Hematoxylin and eosin stained skin tissue slides were
      examined under light microscopy for the presence of AK in close proximity to, or
      giving rise to, cutaneous SCC. RESULTS: Of the 165 cutaneous SCC cases reviewed,
      82.4% (136 out of 165) were found to have concomitant AK giving rise to and/or in
      close proximity to SCC. Of the 136 AK-positive SCC cases, 26.7% (44) were
      identified as superficial SCC arising within an AK (AKSSCC) and 55.7% (92) had AK
      in close proximity to SCC (AK + SCC). Close proximity is defined to include AK
      changes located directly adjacent to (on the shoulder of) SCC, to a maximum
      distance of 8 mm away. CONCLUSIONS: The 82.4% prevalence of concomitant AK and
      cutaneous SCC in our biopsy population suggests a strong correlation between
      these two lesions. The fact that 26.7% of these lesions had SCC arising from AK
      highlights the importance of early recognition and effective treatment for AK.

PMID- 9762819
TI  - Detection and differentiation of causative fungi of onychomycosis using PCR
      amplification and restriction enzyme analysis.
AB  - BACKGROUND: Onychomycosis, a fungal nail infection, has become one of the most
      important dermatophytoses. Unfortunately, a predictably successful diagnostic
      approach to onychomycosis does not yet exist. OBJECTIVE: The purpose of this
      study was to develop a deoxyribonucleic acid (DNA)-based diagnostic method to
      improve the sensitivity and specificity of the detection and differentiation of
      the pathogenic fungi of onychomycosis. METHODS: We attempted to detect fungi in
      the nail using polymerase chain reaction (PCR) primer systems that were designed
      in conserved sequences of the small ribosomal subunit 18S-rRNA genes shared by
      most fungi, and differentiated between species by restriction enzyme analysis of
      the amplified product. RESULTS: Fragments of the gene coding for 18S-rRNA were
      amplified successfully from medically important fungi species, but not from
      normal nails. Restriction fragment length polymorphism patterns using HaeIII
      endonuclease were sufficiently different to allow the recognition of individual
      species. CONCLUSIONS: The PCR-restriction enzyme analysis method appears to be a
      more sensitive detection and identification technique for onychomycosis than
      conventional methods, and has considerable diagnostic value.

PMID- 9762820
TI  - Unusual presentation of cutaneous vasculitis.

PMID- 9762821
TI  - Kasabach-Merritt syndrome in two successive pregnancies.

PMID- 9762822
TI  - Pachydermoperiostosis with cutaneous squamous cell carcinomas.

PMID- 9762823
TI  - Follicular cysts and hyperkeratoses in early mycosis fungoides.

PMID- 9762824
TI  - Solitary hyperpigmented island in a sea of elastosis (anelastosis).

PMID- 9762825
TI  - Localized hyperhidrosis treated with aluminum chloride in a salicylic acid gel
      base.

PMID- 9762826
TI  - A comparison of the efficacy of oral fluconazole, 150 mg/week versus 50 mg/day,
      in the treatment of tinea corporis, tinea cruris, tinea pedis, and cutaneous
      candidosis.

PMID- 9762827
TI  - Response of segmental vitiligo to 0.05% clobetasol propionate cream.

PMID- 9762828
TI  - Early repeeling--a matter of time.
AB  - BACKGROUND: Repeeling after a short interval in medium-depth or deep peeling is
      considered by most experts as hazardous, and is generally contraindicated. Most
      experts recommend an interval of 6 months or more before repeating the same level
      of peel. The results are presented of four patients who underwent repeeling after
      a short interval. METHODS AND RESULTS: All four patients were dissatisfied with
      their first peel (medium-depth peel performed with trichoroacetic acid (TCA)
      35%). Repeelings were performed using two methods: TCA 30-35% (Cases 1-3) and
      unoccluded Baker phenol peel (Case 4). On three occasions (Cases 1-3), the
      patients underwent three peelings at short intervals. All four cases gave
      excellent objective results. CONCLUSIONS: The risk of a second peel shortly after
      the first is not as high as indicated in the literature, and should not be
      automatically ruled out. In a selected group of patients who, for various
      reasons, be persuaded to wait, repeeling after a short interval (2-3 weeks) may
      solve certain problems and may even make the difference between an unhappy
      patient and a satisfied one. In performing repeeling after a short interval, one
      should take into consideration that the skin, particularly the keratin layer, is
      thinner, so that the degree of penetration of the second peel solution and the
      peel depth will be greater. It is possible that the scarring reported after
      repeeling is a result of the disregard of this important factor and,
      consequently, the use of too high a concentration of peel solution in the second
      peel procedure.

PMID- 9762830
TI  - Wound measurement by computer-aided design (CAD): a practical approach for
      software utility.

PMID- 9762829
TI  - Pustular eruption in a malaria patient treated with chloroquine.

PMID- 9762831
TI  - Eccrine squamous syringometaplasia in a patient with phytophotodermatosis.

PMID- 9762832
TI  - Balneotherapy for rheumatic diseases at the Dead Sea.

PMID- 9762834
TI  - Longitudinal melanonychia associated with fluconazole therapy.

PMID- 9762833
TI  - Porphyria cutanea tarda in a human immunodeficiency virus-infected patient:
      treatment with N-acetyl-cysteine.

PMID- 9762835
TI  - Ensuring the survival of the clinician-scientist.

PMID- 9762836
TI  - Cell cycle proteins in glomerular disease.

PMID- 9762837
TI  - Are there new activity markers of glomerular inflammation? A renal pathologist's
      view.

PMID- 9762838
TI  - Molecular genetics and clinical phenotype in heritable disorders of tubular Na+
      transport.

PMID- 9762839
TI  - Molecular pathophysiology of inborn renal Na+ transport defects.

PMID- 9762840
TI  - Pathogenetic and regenerative mechanisms in acute tubular necrosis.

PMID- 9762841
TI  - Histological characteristics of interstitial renal allograft rejection.

PMID- 9762842
TI  - Cloning of a human renal p-aminohippurate transporter, hROAT1.

PMID- 9762843
TI  - Cytoskeletal basis for epithelial polarity.

PMID- 9762844
TI  - Cell volume-regulated gene transcription.

PMID- 9762845
TI  - Angiotensin II receptors in the kidney.

PMID- 9762846
TI  - Neural control of kidney function.

PMID- 9762847
TI  - Epithelial sodium channel and its implication in the control of blood pressure.

PMID- 9762848
TI  - Atomic force microscopy on living cells: aldosterone-induced localized cell
      swelling.

PMID- 9762849
TI  - Transforming growth factor beta signal transduction in the kidney.

PMID- 9762850
TI  - G proteins and hypertension.

PMID- 9762851
TI  - Regulation of NO synthesis in endothelial cells.

PMID- 9762852
TI  - Determination of glomerular permselectivity: is it useful for diagnosis and
      clinical management of patients with glomerular disease?

PMID- 9762853
TI  - Injury mechanisms in vasculitis.

PMID- 9762854
TI  - Target blood pressure in the treatment of essential hypertension.

PMID- 9762855
TI  - Pregnancy-induced alterations in renal function.

PMID- 9762856
TI  - Tubulotoxic mechanisms of ochratoxin A.

PMID- 9762857
TI  - Endothelial cell markers in vasculitis.

PMID- 9762858
TI  - New diagnostic and therapeutic aspects in IgA nephropathy.

PMID- 9762859
TI  - NKF-DOQI guidelines--will they change the treatment of dialysis patients in
      Germany? National Kidney Foundation. Dialyses Outcomes Quality Initiative.

PMID- 9762860
TI  - Causes of coronary heart disease in patients on renal replacement therapy.

PMID- 9762861
TI  - Epidemiology, pathogenesis and therapeutic modalities in hemolytic-uremic
      syndrome.

PMID- 9762862
TI  - Prothrombotic risk factors and acute kidney transplant rejection.

PMID- 9762863
TI  - Effects of botulinum neurotoxin type A on the expression of gephyrin in cat
      abducens motoneurons.
AB  - In this study, we investigated the effects of long-term synaptic blockade on
      postsynaptic receptor clustering at central inhibitory glycinergic synapses. High
      doses of botulinum neurotoxin type A injected in the lateral rectus muscle
      completely abolishes inhibitory postsynaptic potentials onto abducens motoneurons
      within 2 days postinjection, and transmission remains blocked for at least 2
      months. Using this model, we analyzed the expression of gephyrin, a glycine
      receptor clustering protein, on the membrane of motoneuron somata after botulinum
      neurotoxin type A injection in their target muscle. Immunofluorescence or
      electron microscopy immunohistochemistry revealed gephyrin-immunoreactive
      clusters (most < 0.5 microm in diameter) densely covering the surface of control
      abducens motoneurons. Ultrastructurally, presynaptic terminals containing
      flattened synaptic vesicles (F terminals) were found associated with multiple
      gephyrin-immunoreactive postsynaptic densities (average 1.24 gephyrin clusters/F+
      profile). No significant changes in gephyrin-immunoreactive clusters were
      observed at 5 days postinjection, but we found significant reductions (25-40%) in
      the density of gephyrin clusters 19 and 35 days postinjection. Hence, the
      physiological alterations reported in this model precede structural changes on
      postsynaptic receptor cluster density. The decrease in gephyrin-immunoreactive
      clusters was paralleled by reductions in synaptic covering (F+ terminals per 100
      microm of membrane). Presumed inactive F+ terminals that remained attached to the
      motoneuron surface displayed normal gephyrin-immunoreactive clusters; however,
      the pre- and postsynaptic membranes in between synaptic active zones frequently
      appeared separated by enlarged extracellular spaces. We concluded that
      postsynaptic receptor cluster dissolution seemed more directly related to
      terminal retraction than to inactivity alone.

PMID- 9762864
TI  - Cortical connections of the dorsomedial visual area in new world owl monkeys
      (Aotus trivirgatus) and squirrel monkeys (Saimiri sciureus).
AB  - The dorsomedial visual area (DM) is an extrastriate area that was originally
      described in owl monkeys as a complete representation of the visual hemifield in
      a heavily myelinated wedge of cortex just rostral to dorsomedial visual area V2.
      More recently, connections of DM in owl monkeys have been described (Krubitzer
      and Kaas [1993] J. Comp. Neurol 334:497-528). As part of an effort to determine
      whether DM exists in other primates, we compared the architecture, connections,
      and visual topography of DM in owl monkeys and the presumptive DM in squirrel
      monkeys. In both species of New World monkeys, the DM region was more heavily
      myelinated than adjacent cortex, and this region was connected with the first and
      second visual areas, the middle temporal area (MT), the medial area, the ventral
      posterior parietal area, the dorsointermediate area, the dorsolateral area, the
      ventral posterior and ventral anterior areas, the medial superior temporal area,
      the fundal area of the superior temporal sulcus, the inferior temporal cortex,
      and frontal cortex in or near the frontal eye field. In squirrel monkeys, both
      blob and interblob regions of V1 contributed equally to DM, whereas the blob
      regions provided most of the projections to V1 in owl monkeys. In squirrel
      monkeys, connections were also found with cortex on the ventral surface in the
      ventral occipital temporal sulcus. In owl monkeys and squirrel monkeys,
      connections were with both the upper and lower visual field representations in
      V1, V2, and MT, demonstrating that DM contains a complete representation of the
      visual field. These similarities in architecture, connections, and retinotopy
      argue that DM is a visual area of both owl and squirrel monkeys.

PMID- 9762865
TI  - Combinatorial odor discrimination in the brain: attractive and antagonist odor
      blends are represented in distinct combinations of uniquely identifiable
      glomeruli.
AB  - The rules governing the central discrimination of odors are complex and poorly
      understood, but a growing body of evidence supports the hypothesis that olfactory
      glomeruli may represent functionally distinct coding modules in the brain.
      Testing this hypothesis requires that both the functional characteristics and the
      spatial position of the glomerulus under study be uniquely identifiable. To
      address these questions, we examined a specialized array of glomeruli (the
      macroglomerular complex; MGC) in the antennal lobe of male moths that receives
      input from olfactory receptor cells tuned specifically to female-released
      odorants that either promote upwind flight (conspecific sex pheromones) or
      inhibit it (interspecific antagonists). By using a three-dimensional
      reconstruction method based on high-resolution laser-scanning confocal
      microscopy, we generated precise spatial maps of the MGC glomeruli in two related
      noctuid species with similar pheromone chemistry, Heliothis virescens and
      Helicoverpa zea. To determine the breadth of tuning of individual MGC glomeruli
      in processing information about these social signals, we used intracellular
      recording and staining methods to examine the responses of projection (output)
      neurons that innervate MGC glomeruli and that each project an axon to higher
      integrative centers. In both species, a close correspondence was found between
      the odor specificity of the projection neurons and the glomerulus (or glomeruli)
      supplied by them. The binary blend of pheromone components for each species was
      represented by neural activity in only two distinct glomeruli in both H.
      virescens and H. zea. Odorants that antagonize upwind flight when they are added
      to the respective pheromonal blends evoked excitatory activity in output neurons
      restricted to a third glomerulus in the MGCs of both species. In summary, these
      results suggest that the selective activation of different combinations of
      functionally distinct MGC glomeruli is a general means for discriminating these
      specific attractant and antagonist chemical signals in the brain.

PMID- 9762866
TI  - Expression of insulin-like growth factors and corresponding binding proteins
      (IGFBP 1-6) in rat spinal cord and peripheral nerve after axonal injuries.
AB  - Insulin-like growth factors (IGFs) exert trophic effects on several different
      cell types in the nervous system, including spinal motoneurons. After peripheral
      nerve injury, the increased expression of IGFs in the damaged nerve has been
      suggested to facilitate axonal regeneration. Here we have examined the expression
      pattern of mRNAs encoding IGF-1 and and -2, IGF binding proteins (IGFBPs) 1-6 in
      the rat spinal cord and peripheral nerve in three lesion models affecting lumbar
      motoneurons, i.e., sciatic nerve transection, ventral root avulsion, and a cut
      lesion in the ventral funiculus of the spinal cord. The expression was also
      studied in enriched Schwann cell and astrocyte cultures. The injured sciatic
      nerve expressed IGF-1 and IGF-2 as well as IGFBP-4 and IGFBP-5, whereas central
      nervous system (CNS) scar tissue expressed IGF-1, IGFBP-2, and IGFBP-5. IGFBP-6
      mRNA was strongly upregulated in spinal motoneurons after all three types of
      lesions. IGFBP-6-like immunoreactivity was present in motoneuron cell bodies,
      dendrites in the ventral horn, and axons in the sciatic nerve. In line with the
      in vivo findings, cultured Schwann cells expressed IGF-1, IGF-2, IGFBP-4, and
      IGFBP-5 mRNAs, whereas cultured astrocytes expressed IGF-1, IGFBP-2, and IGFBP-5
      mRNAs. These findings show that IGF-1 is available for lesioned motoneurons both
      after peripheral and central axonal lesions, whereas there are clear differences
      in the expression patterns for IGF-2 and some of the binding proteins in CNS and
      peripheral nervous system (PNS) scar tissue. The robust upregulation of IGFBP-6
      mRNA in lesioned motoneurons suggests that this binding protein may be of special
      relevance for the severed cells.

PMID- 9762867
TI  - Cellular distribution of ferritin subunits in postnatal rat brain.
AB  - The normal development of the brain requires finely coordinated events, many of
      which require iron. Consequently, iron must be available to the brain in a timely
      manner and in a bioavailable form. However, the brain also requires stringent
      mechanisms to protect itself from iron-induced oxidative damage. The protein that
      is best suited to making iron available but also adequately protecting the cell
      is the intracellular iron storage protein ferritin. Typically, ferritin is
      composed of 24 subunits of H and L chains, which are functionally distinct. This
      study was undertaken to determine the expression of ferritin subunits during
      normal development of the postnatal rat brain. There is a shift in ferritin
      containing cell types during development from predominantly microglia at
      postnatal day 5 (PND 5) to predominantly oligodendrocytes by PND 30. At PND 5,
      microglia are found throughout gray and white matter areas of the brain, but only
      amoeboid microglia in discrete foci in the subcortical white matter are ferritin
      positive. At PND 15, some oligodendrocytes in the subcortical white matter
      express ferritin, but the majority of ferritin-containing cells within white
      matter are still microglia. By PND 30, the predominant ferritin-containing cell
      type within white matter are oligodendrocytes. Generally, the cellular
      distribution of both ferritin subunits were identical with one major exception; H
      ferritin, but not L-ferritin, was present in neuronal nuclei in the cortex. These
      data suggest that microglia play a role in brain iron homeostasis during normal
      postnatal development and may influence myelination by competing with
      oligodendrocytes for iron.

PMID- 9762868
TI  - Postmortem tracing reveals the organization of hypothalamic projections of the
      suprachiasmatic nucleus in the human brain.
AB  - The suprachiasmatic nucleus (SCN) is a small structure considered to be the site
      of the major circadian pacemaker of the mammalian brain. Disturbances in human
      biological clock function may occur in several diseases, such as Alzheimer's
      disease, sleep problems, and seasonal depression. Since basic knowledge of the
      anatomical connections of the human SCN is limited due to the lack of suitable
      neuroanatomical tracing methods, the understanding of physiological mechanisms of
      human SCN function has obviously been hampered. In the present study, the
      hypothalamic connections of the human SCN were revealed for the first time with a
      newly developed in vitro postmortem anterograde tracing method. The human SCN was
      found to be connected with nuclei in the hypothalamus that are involved in
      hormone secretion, cardiovascular regulation, and behavior activity. These human
      SCN projections appear to follow the same general patterns as those in the rodent
      brain. This homology may indicate an evolutionary conservation of the SCN
      projections from rodent to human. Through these connections, the human SCN may
      transmit its circadian information to regulate hormone secretion, body
      temperature, and behavioral functions as it does in animal species. In addition,
      the postmortem tracing technique may be a valuable tool that will contribute to
      our understanding of anatomical connections in the human brain, and may have
      other applications in the research on the physiology and pathology of the human
      brain.

PMID- 9762869
TI  - Synaptic changes in the perineal motoneurons of aged male rats.
AB  - Cholera toxin-horseradish peroxidase (CT-HRP) was injected into the
      bulbocavernosus muscles of young (2 months of age) and old (19-20 months of age)
      male rats, and animals were killed 2 days later. The spinal cords containing the
      spinal nucleus of the bulbocavernosus (SNB) were dissected, processed with a
      modified tetramethylbenzidine method for visualization of retrogradely
      transported CT-HRP, and examined ultrastructurally. Neuronal structures apposing
      the membranes of 120 CT-HRP-labeled SNB motoneurons were analyzed by measuring
      the percentage of somatic membranes covered by synaptic contacts, synaptoid
      contacts, and neuron-neuron contacts. Most of the neuronal structures in the
      young and old SNB motoneurons consisted of synaptic contacts. The mean percentage
      of somatic membranes covered by synapses in old rats was significantly smaller
      than that in young ones. Size and number of synaptic contacts per unit length of
      somatic membranes in old animals were also significantly reduced. Plasma levels
      of testosterone in old males were significantly smaller than those in young ones.
      These age-related changes in synaptic inputs to SNB motoneurons and plasma levels
      of androgen seem to correlate with aging of the SNB system.

PMID- 9762870
TI  - Increased number and size of dendritic spines in ipsilateral barrel field cortex
      following unilateral whisker trimming in postnatal rat.
AB  - The barrel field area of the primary somatosensory cortex of rodents is a fertile
      ground for investigating experience-dependent plasticity and its mechanisms,
      because the neurons in its layer IV are distributed in groups (barrels) which
      correspond somatotopically to the vibrissae of the contralateral facial pad.
      After removal of three rows of whiskers from the right facial pad of young rats
      during the first two postnatal months, we looked for eventual changes in
      dendritic spine number and morphology in the corresponding barrels ipsi- and
      contralateral to the deprivation. Intact littermate controls were also examined.
      Spine number was determined by means of the unbiased disector method in electron
      micrographs from serial thin sections processed for post-embedding gamma
      aminobutyric acid (GABA) immunocytochemistry. The volume and surface area of
      spine head, surface area of postsynaptic density and length of spine neck were
      measured from computerized three-dimensional reconstructions. Even though there
      was no significant side-to-side difference in the numerical density of dendritic
      spines in the experimental animals, the total number of spines in the ipsilateral
      barrels had increased by 67%, in view of the greater thickness of layer IV on
      this side. Moreover, spine head volume and surface area of postsynaptic densities
      were increased, and the length of spine neck was reduced in the ipsilateral
      compared to the contralateral cortex, and similar differences were noticeable
      between ipsilateral and control cortex. These changes apparently involved not
      only the predominant population of relatively small, dendritic spines innervated
      by asymmetrical synaptic terminals, but also the relatively small contingent of
      larger spines receiving symmetrical synapses formed by GABA terminals. The most
      likely explanation for such ipsilateral changes was an increased use of the
      intact (contralateral) facial pad during postnatal life, in keeping with the
      notion that activation of a peripheral sensory apparatus during the early
      postnatal period may have profound effects on the neuronal morphology and
      structural design of the primary somatosensory cortex. A possible mechanism in
      this case might be the excessive early activation of thalamic afferents,
      resulting in increased production of trophic factors, such as brain-derived nerve
      growth factor.

PMID- 9762871
TI  - Cells of origin of the trigeminohypothalamic tract in the rat.
AB  - Recent studies have demonstrated that a large number of spinal cord neurons
      convey somatosensory and visceral nociceptive information directly from cervical,
      lumbar, and sacral spinal cord segments to the hypothalamus. Because sensory
      information from head and orofacial structures is processed by all subnuclei of
      the trigeminal brainstem nuclear complex (TBNC) we hypothesized that all of them
      contain neurons that project directly to the hypothalamus. In the present study,
      we used the retrograde tracer Fluoro-Gold to examine this hypothesis. Fluoro-Gold
      injections that filled most of the hypothalamus on one side labeled approximately
      1,000 neurons (best case = 1,048, mean = 718 +/- 240) bilaterally (70%
      contralateral) within all trigeminal subnuclei and C1-2. Of these neurons, 86%
      were distributed caudal to the obex (22% in C2, 22% in C1, 23% in subnucleus
      caudalis, and 18% in the transition zone between subnuclei caudalis and
      interpolaris), and 14% rostral to the obex (6% in subnucleus interpolaris, 4% in
      subnucleus oralis, and 4% in subnucleus principalis). Caudal to the obex, most
      labeled neurons were found in laminae I-II and V and the paratrigeminal nucleus,
      and fewer neurons in laminae III-IV and X. The distribution of retrogradely
      labeled neurons in TBNC gray matter areas that receive monosynaptic input from
      trigeminal primary afferent fibers innervating extracranial orofacial structures
      (such as the cornea, nose, tongue, teeth, lips, vibrissae, and skin) and
      intracranial structures (such as the meninges and cerebral blood vessels)
      suggests that sensory and nociceptive information originating in these tissues
      could be transferred to the hypothalamus directly by this pathway.

PMID- 9762872
TI  - Combining studies using effect sizes and quality scores: application to bone loss
      in postmenopausal women.
AB  - This article presents a random effects model that uses effect sizes (ES) and
      quality scores to integrate results from investigations. An empirical example is
      given with data obtained from a meta-analysis on the effectiveness of physical
      activity in the prevention of bone loss in healthy postmenopausal women. A
      Medline search was performed to locate relevant studies published in French or
      English between January 1966 and May 1996. Three independent reviewers extracted
      data from studies. Effect sizes were calculated according to the method of Hedges
      and Olkin. A modified version of Chalmers' scale was utilized to calculate
      quality scores. DerSimonian and Laird's method with incorporation of the quality
      scores was used to estimate the overall effect size. Quality scores and the
      inverse of the variances were included as weights when combining studies. The
      overall estimate and standard error (SE) of the effect of physical activity on
      spinal bone mineral density loss in healthy postmenopausal women was ESoverall =
      0.4263 (1.1361). When compared to other meta-analysis methods such as the fixed
      effects model and the model of DerSimonian and Laird without the quality score
      (DL), the new model generated comparable estimators (fixed effects model's
      ESoverall (SE) = 1.2724 (0.0139), DLs ESoverall (SE) = 0.3958 (1.2370)). Due to
      the heterogeneity that existed between studies, a random effects model was more
      appropriate then a fixed effects model. However, it resulted in wider confidence
      intervals, as expected. It was shown empirically that the model using quality
      scores generated narrower confidence intervals than the model of DL alone. The
      inclusion of covariates such as quality scores in meta-analyses permits the
      quantification of the variation between studies.

PMID- 9762873
TI  - Using binary logistic regression models for ordinal data with non-proportional
      odds.
AB  - The proportional odds model (POM) is the most popular logistic regression model
      for analyzing ordinal response variables. However, violation of the main model
      assumption can lead to invalid results. This is demonstrated by application of
      this method to data of a study investigating the effect of smoking on diabetic
      retinopathy. Since the proportional odds assumption is not fulfilled, separate
      binary logistic regression models are used for dichotomized response variables
      based upon cumulative probabilities. This approach is compared with polytomous
      logistic regression and the partial proportional odds model. The separate binary
      logistic regression approach is slightly less efficient than a joint model for
      the ordinal response. However, model building, investigating goodness-of-fit, and
      interpretation of the results is much easier for binary responses. The careful
      application of separate binary logistic regressions represents a simple and
      adequate tool to analyze ordinal data with non-proportional odds.

PMID- 9762874
TI  - Selective opportunistic screening for hypercholesterolemia in primary care
      practice.
AB  - OBJECTIVES: To assess the performance of selective opportunistic screening in a
      primary care group practice. DESIGN: Cross-sectional survey of coronary heart
      disease risk factors and retrospective chart audit of cholesterol testing.
      SETTING: Capitation-funded primary care group practice in Ontario, Canada.
      SUBJECTS: 7785 enrolled patients between the ages of 20 and 69 years.
      INTERVENTION: Protocol-based selective opportunistic screening program for
      hypercholesterolemia of 45 months duration. MAIN OUTCOME MEASURES: Targeting
      (proportion of screening tests that were appropriate), coverage (proportion of
      those meeting screening criteria who had a screening test performed), over
      screening (proportion of those not meeting screening criteria who had a screening
      test performed), and screening ratio (likelihood that a screening test was
      performed on an individual who met screening criteria rather than one who failed
      to meet screening criteria). RESULTS: 64.7% of patients tested met the practice
      criteria for screening. 37.7% of patients who met the practice screening criteria
      were tested and 24.9% of those not meeting practice screening criteria had a
      cholesterol test performed. The screening ratio was 1.52. CONCLUSION: Our
      findings bring into question the effectiveness of opportunistic approaches to
      preventive care.

PMID- 9762875
TI  - Testing the measurement properties of the Short Form-36 Health Survey in a frail
      elderly population.
AB  - The Short Form-36 Health Survey (SF-36) is a widely used measure of health
      related quality of life, however, its suitability for frail older persons is not
      well documented. This study examines the measurement properties of the SF-36 in a
      frail older patient population. Patients consecutively admitted to two geriatric
      services (n = 146) were administered the SF-36 and comparative measures on
      admission and discharge. Internal consistency (0.75-0.91) and test-retest
      reliability (0.24-0.80) did not meet standards for clinical application of the
      tool. Four subscales were moderately correlated with comparative measures
      (Physical Function 0.53 to -0.76; Bodily Pain -0.61; Vitality -0.58; Mental
      Health -0.63). The results of effect size, standardized response mean, and
      relative efficiency statistics were consistent in documenting only minimal change
      for the SF-36 subscales. The SF-36 appears to be reliable and valid, although its
      ability to monitor clinical change for frail older patients is questionable.

PMID- 9762876
TI  - Predictors of sex hormone levels among the elderly: a study in Greece.
AB  - This study examines the relationship between a series of epidemiologic parameters
      (age, height, body mass index (BMI), smoking, alcohol consumption, and coffee
      drinking) and serum concentrations of testosterone, estradiol, sex hormone
      binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAS). Among 52
      healthy, elderly Greek men, we observed that serum levels of DHEAS decreased with
      increasing age [19% decline per 5-year increase in age, 95% CI, -2.1-(-33.5)],
      obesity [48% decline for BMI >30 kg/m2 compared to <27 kg/m2, CI, -15.7-(-68.7)],
      and current smoking [37% decline compared to nonsmokers, CI, -9.5-(-57.2)].
      Estradiol concentrations increased with increasing BMI [77.1% increase for BMI
      >30 kg/m2 compared to <27 kg/m2, CI, -12.0-256.3], alcohol drinking [66% increase
      for > or = 7 glasses/week compared to <7 glasses/week, CI, 4.4-164.4], and coffee
      drinking [59% increase for > or = 14 cups/week compared to > or = 14 cups/ week,
      CI, -0.5-155.9], and decreased among current smokers [40% decline compared to
      nonsmokers, CI, -64.9-0.8]. SHBG was marginally positively associated with
      increasing age [13% increase per 5 years, CI, -0.5-29.6]. Testosterone was
      significantly related only to current smoking [27% decline compared to
      nonsmokers, CI, -45.4-(-3.1)]. These findings suggest that several variables
      appear to be associated with sex steroid levels and the influence of these
      findings on the occurrence of hormone-related conditions warrants further
      exploration.

PMID- 9762877
TI  - Effectiveness of cataract surgery in Barcelona, Spain site results of an
      international study. Barcelona I-PORT investigators. International Patient
      Outcomes Research Team.
AB  - OBJECTIVES: To describe the impact of cataract surgery on visual function and
      health status in terms of clinical indicators as well as perceived health and
      functional capacity, and to identify patient characteristics and differences in
      clinical management that might affect outcomes. SUBJECTS AND METHODS:
      Observational longitudinal study of a cohort of 218 patients aged 50 or older
      undergoing first eye cataract surgery. Patients were evaluated pre- and
      postoperatively by clinical examinations (visual acuity [VA], ocular and medical
      comorbidity) and standardized telephone interviews. Main outcome measures
      included: the VF-14 Visual Function Index, the Cataract Symptom Score (CSS), the
      Sickness Impact Profile (SIP), and global measures of patients' trouble and
      satisfaction with vision. RESULTS: Significant improvement in all outcomes
      measures were observed at 4 months postoperatively (P < 0.001). However, the
      proportion of improved patients varied according to the outcome considered: VA
      (87%), CSS (72%), VF-14 (62%), and SIP (38%). Patient characteristics associated
      with higher a level of improvement were: worse preoperative visual function (VA,
      CSS, VF-14) (P < 0.001), less ocular comorbidity (P < 0.05), less postoperative
      complications (P < 0.05) and better preoperative general health status (SIP) (P <
      0.01). The differences in clinical management were not associated with the
      outcomes (effectiveness) of surgery. CONCLUSIONS: A large proportion of patients
      benefit from cataract surgery, the greatest gain corresponding to visual function
      rather than to general health status. Since effectiveness of surgery is unrelated
      to operative procedures, less costly practices (i.e., day case surgery and loco
      regional anesthesia) should be promoted.

PMID- 9762878
TI  - Clinical outcomes of localized melanoma of the foot: a case-control study.
AB  - The controversy over whether melanoma of the foot has a poorer prognosis than
      melanoma of the leg remains unresolved. This investigation used a case-control
      design to address this issue. This design consisted of a survival analysis of 119
      cases with localized melanoma of the foot and 238 controls with localized
      melanoma of the leg that were matched on prognostic factors including tumor
      thickness, ulceration, surgical treatment, gender, year of diagnosis, and age.
      There was a statistically significant difference between the survival rates of
      cases and controls. The 5-year survival rate for cases was 74.3% compared to
      85.2% for controls. At 10 years, the survival rate was 63.6% for cases and 77.2%
      for controls. Cases experienced a higher percentage of distant recurrences than
      controls. These results imply that patients with melanoma of the foot have a
      poorer survival than patients with melanoma of the leg after controlling for
      prognostic factors.

PMID- 9762879
TI  - Appendectomy in Sweden 1989-1993 assessed by the Inpatient Registry.
AB  - We analyzed all appendectomies in Sweden 1989-1993 (n = 60,306) recorded in the
      national Inpatient Registry. Our focus was on diagnostic accuracy, incidence rate
      of appendicitis, perforative appendicitis, and length of stay by day of admission
      and hospital category. The incidence rate of appendectomy decreased by 9.8% in
      women compared to 4.1% in men. Since the number of patients with an end diagnosis
      of appendicitis remained almost constant, diagnostic accuracy increased each
      year. This was more pronounced in women than men, seen in all hospital
      categories, and was higher for those admitted during periods of low capacity
      (weekends/ holidays). Perforated appendicitis did not increase. Duration of
      hospital stay decreased continuously, especially among the oldest. We found no
      indications of an increased frequency of complications, such as increases in the
      incidence rate of perforations or in the length of stay.

PMID- 9762880
TI  - Health status measurement in Toxic Oil Syndrome.
AB  - Toxic Oil Syndrome (TOS) is a previously unreported condition which affected more
      than 20,000 people in Spain in 1981 and whose natural history is unknown. In 1993
      94, a stratified random sample of 1400 survivors was drawn to measure their
      health status through clinical examination and their self-perception of well
      being through the Nottingham Health Profile Questionnaire (NHPQ). Two-thirds of
      the sample population responded; indirect estimates suggest that selection bias
      was limited. Clear and intermediate signs of neuropathy were found in one-fifth
      and one-half of the patients, respectively. One-fourth and one-sixth showed some
      degree of scleroderma and contractures. All conditions were more frequent in
      women than in men and in age >50 than in younger ages. Although no concurrent
      control group was included in the study, prevalences of these conditions are well
      above expectations and are largely attributable to TOS. NHPQ scores increased
      with age in both sexes up to age 50, after which they reached a plateau (with
      values around 48 in men and 62 in women). Scores were associated to the
      occurrence of peripheral neurological changes, contractures, and scleroderma-like
      conditions. A multivariate analysis indicated age, sex, and severity of
      neurological conditions as major determinants of the NHPQ scores. This overall
      pattern of findings is peculiar to TOS and differs from the typical post-disaster
      nonspecific syndrome.

PMID- 9762881
TI  - Effect of the method of administration, mail or telephone, on the validity and
      reliability of a respiratory health questionnaire. The Spanish Centers of the
      European Asthma Study.
AB  - The European Community Respiratory Health Survey (ECRHS), a multinational survey,
      assesses and compares the prevalence of asthma among subjects, aged 20 to 44, in
      several European areas. In Spain, some participating centers have used mail and
      telephone as methods of questionnaire administration. The objective of the
      present study was to determine whether the validity and reliability of the
      questionnaire differed by method of administration. Reliability of the
      questionnaire was measured with the kappa index and the odds ratio of agreement,
      and validity with the sensitivity and specificity. This study found differences
      in the reliability of the questionnaires although these differences were more
      related to the questions themselves than to the method of administration. Among
      men, but not women, mailed questionnaires were more sensitive and telephone
      questionnaires more specific. We hypothesize that these differences in validity
      were due to the self-selection to more severe symptomatic subjects replying
      earlier and therefore to the mailed questionnaire. Combining different methods of
      administration was useful as it increased participation and was an adequate
      procedure to obtain information of good quality.

PMID- 9762882
TI  - Assessing the feasibility of using computerized pharmacy refill data to monitor
      antidepressant treatment on a population basis: a comparison of automated and
      self-report data.
AB  - This article compares self-report and automated data as measures of dose and
      duration of antidepressant use in order to assess the feasibility of using
      automated pharmacy data in a disease management context. We used self-report and
      computerized refill data to identify two treatment failures-premature
      discontinuation of the medication and sub-optimal dosages-at time points 1 and 4
      months after initiation of antidepressant therapy. The sources showed modest
      agreement regarding identification of current users at 1 month (kappa = .33);
      agreement was high at 4 months (kappa = .72). Agreement regarding dosage adequacy
      was also higher later in treatment, with kappas of .52 and .65 at 1 and 4 months,
      respectively. The two sources showed high agreement on an overall measure of
      acute phase treatment adequacy (kappa = .80). Data completeness was another
      outcome, with data on current users and overall treatment adequacy generally
      available from computerized files, data on dose less so. Automated pharmacy data
      appear to be a feasible means of monitoring treatment adequacy and quality of
      care as part of a disease management approach to improving care for populations
      of patients.

PMID- 9762883
TI  - Division of the colorectum into anatomic subsites: why and where?

PMID- 9762884
TI  - Cancer and complexity: correlations and complementarity.

PMID- 9762885
TI  - Local treatment of abdominal wound reduces tumor implantation.
AB  - BACKGROUND AND OBJECTIVES: Pneumoperitoneum increases the trocar-site tumor
      implantation rate using a human colon cancer cell line in a hamster model. The
      purpose of this study was to determine whether local treatment of trocar sites
      with potential tumoricidal agents can inhibit tumor implantation after
      pneumoperitoneum. METHODS: GW-39 human colon cancer cells (0.5 ml of 2.5% v/v;
      8.0 x 10(5) cells) were injected throughout the abdomen of 133 Golden Syrian
      hamsters through a midline incision. The animals were randomized to receive
      either untreated 5-mm trocars in each abdominal quadrant (group I control, n =
      49), trocars dipped in 10% povidone-iodine (group II, n = 53), or trocars coated
      with 1% silver sulfadiazine (group III, n = 51). The midline wounds were also
      coated with the respective agents before closing. Pneumoperitoneum was then
      maintained at 10 mmHg for 10 min, after which the trocar wounds were closed. In
      group II, the trocar sites were treated with a coat of povidone-iodine after the
      trocars were withdrawn and before closing. Gross and microscopic tumor implants
      were analyzed at 7 weeks postoperatively. RESULTS: The rate of tumor cell
      implantation at trocar sites was reduced from 93% (172/184) in the control group
      to 75% (126/168) and 78% (141/180) in groups II and III, respectively (P <
      0.0001). Fewer palpable tumors were detected in groups II and III (40% and 23%,
      respectively) than in the control group (72%, P < 0.0001). Mean tumor mass in
      group III (0.4+/-0.1 g), but not in group II (1.0+/-0.2 g), was significantly
      less than that in the control group (1.3+/-0.1 g, P < 0.01). Overall tumor
      involvement of the larger midline wound was similar for all groups (I = 80%, II =
      79%, III = 71%). However, palpable tumors were identified more frequently in
      group I (67%) than in groups II and III (43%, P < 0.05; 22%, P < 0.01,
      respectively). CONCLUSION: Pretreatment of abdominal wounds with povidone-iodine
      or silver sulfadiazine can reduce tumor implantation after pneumoperitoneum in a
      hamster model.

PMID- 9762886
TI  - Lymph node status assessment for gastric carcinoma: is the number of metastatic
      lymph nodes really practical as a parameter for N categories in the TNM
      Classification? Tumor Node Metastasis.
AB  - BACKGROUND AND OBJECTIVES: The anatomical extent of nodal metastasis has been
      replaced by the number of metastatic nodes as a key indicator of prognosis (pN
      categories) in the fifth edition of Tumor Node Metastasis Classification for
      gastric carcinoma by the International Union Against Cancer. The rate of
      metastatic nodes among all the nodes harvested is also a good prognostic factor.
      The object of this study is to evaluate which of the three parameters for the
      assessment of nodal status is the most appropriate for use in the stage
      classification. METHODS: Retrospective survival analyses were performed in 656
      consecutive patients with advanced gastric carcinoma who underwent D2
      lymphadenectomy and for whom histopathologic data of more than 20 lymph nodes
      were available. RESULTS: Although all three systems served well to classify the
      patients into distinct groups in terms of survival curves, stratification by the
      number of metastatic nodes was vulnerable to stage migration because of
      differences in the number of lymph nodes harvested. Such stage migration was not
      evident for the other two parameters. CONCLUSIONS: Lymph node metastatic rate can
      be recommended as an internationally applicable parameter for lymph node
      involvement of gastric carcinoma.

PMID- 9762887
TI  - Expression of insulin-like growth factor receptor, IGF-1, and IGF-2 in primary
      and metastatic osteosarcoma.
AB  - BACKGROUND AND OBJECTIVES: We have previously shown that insulin-like growth
      factor (IGF)-responsive murine sarcomas demonstrate inhibition of local and
      metastatic disease growth when implanted in an IGF-deficient host animal. In this
      experiment, we tested whether IGF receptor (IGF-R) and ligands were expressed in
      human primary and metastatic osteosarcomas. METHODS: Fifty-two specimens of human
      osteosarcoma tumor from 48 patients were assayed for IGF-R, IGF-1, and IGF-2
      using reverse transcriptase polymerase chain reaction. RESULTS: Twenty-one of 46
      tumors analyzed had levels of expression of IGF-R greater than or equal to the
      positive control cell line. Twenty-seven of 44 expressed levels of IGF-1 greater
      than or equal to the positive control, as did 21 of 38 cases assayed for IGF-2.
      No differences were found between 40 primary tumor samples and 12 metastatic
      lesions in mean levels of IGF-R, IGF-1, or IGF-2. There was a moderately strong
      correlation between expression of IGF-R and IGF-1, suggesting that autocrine
      stimulation may be an important mechanism for stimulation of osteosarcoma
      proliferation. CONCLUSIONS: A significant proportion of osteosarcoma tumors
      express IGF-R and ligands. Higher levels of expression were not correlated with
      metastatic lesions.

PMID- 9762888
TI  - Evaluation of argyrophilic nucleolar organizer region and proliferating cell
      nuclear antigen in colorectal cancer.
AB  - BACKGROUND AND OBJECTIVES: Information on cellular proliferation is gaining
      importance for predicting prognosis in several cancers. To clarify the
      clinicopathological significance of argyrophilic nucleolar organizer region
      (AgNOR), proliferating cell nuclear antigen (PCNA), and DNA ploidy pattern, we
      studied their correlations with clinicopathological factors in colorectal cancer.
      METHODS: Fifty-two patients with colorectal cancer were examined by AgNOR
      staining, immunohistochemical study of PCNA expression, and DNA flow cytometry.
      RESULTS: The AgNOR score and the PCNA labeling rate (PCNA LR) were significantly
      higher in patients with deep invasion (P = 0.0072, P = 0.0355), liver metastasis
      (P = 0.0022, P = 0.0001), and Dukes D classification (P = 0.0002, P = 0.0001)
      than in patients without these factors. In patients with high AgNOR score (>3.83)
      or with high PCNA LR (>48.8), prognosis was significantly worse (P = 0.0002, P =
      0.0123) than in those with low AgNOR score (<3.83) or in those with low PCNA LR
      (<48.8), respectively. No significant association was observed between AgNOR
      score and PCNA LR. Combined analysis revealed that the survival curve for
      patients with high AgNOR score and high PCNA LR was significantly lower (P =
      0.0156) than that for patients with high AgNOR score and low PCNA LR. There was
      no significant correlation between DNA ploidy pattern and clinicopathological
      findings. CONCLUSIONS: PCNA LR and AgNOR score were correlated not only with
      local progression but also with metastasis. Their determination provided useful
      prognostic information, and these parameters are probably independent. Their
      simultaneous determination was useful for accurate evaluation of prognosis. The
      value of DNA ploidy pattern was uncertain.

PMID- 9762889
TI  - Colorectal sarcoma: analysis of failure patterns.
AB  - BACKGROUND AND OBJECTIVES: Colorectal sarcomas (CRS) are rare and their treatment
      remains controversial, especially for those located in the rectum. The aim of
      this paper is to evaluate our experience, with special emphasis on the failure
      pattern after surgical therapy alone or combined with postoperative radiotherapy.
      MATERIALS AND METHODS: The medical records and histological slides of 13 CRS
      patients treated between 1986 and 1996 were reviewed retrospectively. RESULTS:
      The patients included eight males and five females, with a median age of 54
      years; nine of their primary tumors were located in the rectum, and four in the
      colon. The histologies were leiomyosarcoma in nine cases and malignant fibrous
      histiocytoma in four cases. Surgical treatment consisted of anatomical colectomy
      (four); local excision (three); abdominoperineal resection (APR)(two); low
      anterior resection (LAR)(two); LAR en bloc with the prostate (one), and total
      pelvic exenteration (one). One operative death occurred. The median size of the
      tumors was 8 cm (range, 5-40). The tumors were graded as low, three, and high,
      ten. The median follow-up was 24 months. Eight patients in the overall group
      developed recurrences as follows: local, three; local and distant, three, and
      distant, two. Five out of nine patients with rectal sarcoma received adjuvant
      postoperative radiotherapy (PRT). Local recurrence occurred in 20% (1/5) of those
      who received PRT, and in 100% (3/3) of those who did not. The overall 5-year
      survival was 40%, and the 5-year survival for patients with low-grade tumors was
      66%, as compared with 22% for those with high-grade tumors. CONCLUSIONS: The
      patterns of failure in CRS are combined in both local and distant sites. However,
      our results suggest that in rectal sarcoma, the use of surgery + PRT may reduce
      the local recurrence rate; in selected patients, it may allow for anal sphincter
      preservation.

PMID- 9762890
TI  - Therapeutic significance of palliative operations for gastric cancer for survival
      and quality of life.
AB  - BACKGROUND AND OBJECTIVES: There have been few reports on the objective
      assessment of quality of life (QOL) in patients with gastric cancer following
      palliative operations. The benefit of a palliative operation for survival and QOL
      of patients with gastric cancer is not clear. METHODS: Survival and hospital-free
      survival (HFS), which is considered to be one objective indicator of QOL, were
      studied in 95 patients undergoing palliative operations for gastric cancer.
      Univariate and multivariate analyses were used to determine the clinicopathologic
      factors potentially related to survival of patients. RESULTS: In univariate
      analysis, palliative gastrectomy and absence of peritoneal dissemination were
      significantly correlated with better survival. The significance of palliative
      gastrectomy for survival was, therefore, evaluated for various degrees of
      peritoneal dissemination: P0 no dissemination; P1, metastasis to the adjacent
      peritoneum; P2, a few scattered metastases to the distant peritoneum; and P3,
      numerous metastases. Survival and achievement of HFS for 3 months or longer were
      higher following palliative gastrectomy than gastrojejunostomy. Among
      gastrectomies, however, total gastrectomy performed in patients with P2 or P3
      showed a poorer outcome for survival and HFS than total gastrectomy performed
      with P0 or P1 and distal gastrectomy. CONCLUSIONS: As a palliative measure,
      gastrojejunostomy and total gastrectomy performed with P2 or P3 peritoneal
      dissemination had no beneficial effect on the prolongation of survival or
      improvement of QOL of patients with gastric cancer.

PMID- 9762891
TI  - Fluorodeoxyuridine causes bilomas after hepatic cryotherapy.
AB  - BACKGROUND AND OBJECTIVES: Hepatic cryotherapy is a method of in situ
      cytodestruction used for unresectable liver tumours that can be combined with
      regional cytotoxic administration. We have used intra-arterial chemotherapy with
      5-fluorouracil (5-FU) after hepatic cryotherapy but changed to 5
      fluorodeoxyuridine (FUDR) because of the arterial toxicity of 5-FU. A new
      complication was seen. METHODS: A retrospective case note study was performed of
      130 patients who had undergone hepatic cryotherapy followed by regional
      chemotherapy at our centre. Seven patients received FUDR; 123 received 5-FU.
      RESULTS: Biloma at the cryotherapy sites was seen in three patients in the FUDR
      group; two other patients in this group had other types of hepatic collection.
      Our previous experience with intra-arterial 5-FU in 123 patients after hepatic
      cryotherapy showed no evidence of this syndrome. CONCLUSIONS: Intra-arterial FUDR
      should not be used after hepatic cryotherapy, at least during the immediate
      postoperative period.

PMID- 9762892
TI  - Richter hernia of the stomach.
AB  - A case report is presented of Richter hernia of the stomach, after en bloc
      excision of multiple organs for sarcoma of the left upper quadrant of the
      abdomen. To our knowledge this is the first case reported in the literature. The
      conditions for the development of this hernia are : (1) the freeing of the
      greater curvature of the stomach (following removal of the spleen and tail of the
      pancreas); and (2) fascial dehiscence following a left thoracoabdominal incision
      involving rib resection.

PMID- 9762893
TI  - Surgical management of adrenal metastases from lung cancer.
AB  - BACKGROUND AND OBJECTIVES: Adrenal metastases from lung cancer usually indicate
      systemic disease and incurability. However, a small subset of patients with
      isolated adrenal metastases may achieve long-term survival with aggressive
      surgical resection of the adrenal gland. To clarify the role of adrenalectomy for
      metastatic lung cancer, we undertook a review of the published literature on this
      topic. METHODS: The English-language medical literature was searched for papers
      reporting surgical resection of adrenal metastases from lung cancer. Eleven
      articles were retrieved and their data pooled for analysis. RESULTS: Sixty
      patients (including seven previously reported from our institution) formed the
      basis of this collective review. Thirty-two patients pooled from small series and
      case reports had a median survival of 24 months, and approximately one-third were
      5-year survivors. Twenty-eight patients reported in two large series had a less
      favorable survival (approximately 14 months median survival). CONCLUSIONS:
      Surgical resection of isolated adrenal metastases from lung cancer appears to
      have a modest survival advantage over nonoperative therapy, and it occasionally
      results in long-term survival. However, the relatively encouraging survival
      results reported in the literature could be related to careful patient selection
      for this aggressive therapy, publication bias in favor of positive treatment
      outcomes, or a combination of the two. Nevertheless, the results are encouraging
      enough to justify further investigation of this aggressive treatment strategy.
      Practical guidelines for management are proposed.

PMID- 9762894
TI  - Identification of mouse crystallins in 2D protein patterns by sequencing and mass
      spectrometry. Application to cataract mutants.
AB  - The eye lens proteins of the mouse were separated into 1940 polypeptide spots by
      two-dimensional electrophoresis in large gels. All 16 crystallins ubiquitous in
      mammals were identified by protein sequencing and mass spectrometry except for
      (gamma)-F, which shows an almost identical sequence with (gamma)-E. Two
      crystallins, (beta)-A2 and (gamma)-S, were shown for the first time to occur in
      the mouse lens. An investigation of the murine cataract mutant Cat2(nop)((gamma)
      B gene) demonstrated that a monogenic mutation might affect a broad spectrum of
      proteins.

PMID- 9762895
TI  - Genomic structure and promoter analysis of the p62 gene encoding a non
      proteasomal multiubiquitin chain binding protein.
AB  - p62 is a novel immediate early response gene encoding a ubiquitin chain binding
      protein. To investigate the mechanism of p62 gene expression, we isolated and
      characterized the 20 kb long human p62 gene. The p62 gene contains seven introns
      and eight exons. The splice sites conformed to the GT/AG rule, except introns 6
      and 7 which used the unusual GC dinucleotides. The p62 promoter is TATA-less, and
      357 nucleotides of the 5'-flanking region contain basic machineries for
      transcription. A reporter gene linked to 1800 nucleotides of the 5'-flanking
      region was rapidly activated by various extracellular signals. The presence of a
      CpG island as well as multiple binding sites for SP-1, AP-1, NF-kappaB, and Ets-1
      family in the promoter region supports the regulated activation of the p62 gene.

PMID- 9762896
TI  - Expression of alternatively spliced human latent transforming growth factor beta
      binding protein-1.
AB  - Latent transforming growth factor beta binding protein-1 (LTBP1) is important in
      regulating the localisation and activation of transforming growth factor
      beta(TGFbeta). Three forms of LTBP1 mRNA have previously been described, LTBP1L,
      LTBP1S and LTBPdelta53. Here, we have analysed the LTBP1 coding sequence and
      identified two other spliced forms, LTBP1delta55 and LTBP1delta41. LTBP1delta55
      is a short form of LTBPIL which lacks 55 amino acids including two consensus N
      glycosylation sites and LTBP1delta41 is a form of LTBP1 which lacks the 12th EGF
      like repeat. Furthermore, sequencing of genomic clones showed that splicing to
      generate LTBP1L occurs using an intra-exonic 3' splice acceptor site in the first
      coding exon of LTBP1S and that LTBP1delta55 arises from the alternative use of an
      exonic 3' splice acceptor site at the end of the following intron. LTBP1delta41
      arises from skipping the exon which encodes the 12th EGF-like repeat.
      LTBP1delta55 and LTBP1delta41 mRNA are expressed in a wide variety of human
      tissues but the proportions of each splice form vary in the tissues.

PMID- 9762897
TI  - Isolation and sequence of cDNA encoding the motilin precursor from monkey
      intestine. Demonstration of the motilin precursor in the monkey brain.
AB  - The motilin precursor cDNA has been isolated and sequenced from a cDNA library
      prepared from monkey small intestine. The sequence indicates a 345 bp open
      reading frame, a 63 bp 5' untranslated region and a 154 bp 3' untranslated
      region. The sequence encodes a 115 amino acid motilin precursor composed of a 25
      amino acid signal peptide, the 22 amino acid motilin peptide and a 68 amino acid
      motilin associated peptide (MAP). Compared with the human motilin precursor cDNA,
      there are two amino acid substitutions in the signal peptide, one in motilin and
      four in the MAP. The presence of the motilin precursor in hypothalamus,
      hippocampus and cerebellum was demonstrated by RT-PCR.

PMID- 9762898
TI  - Age-related increased susceptibility of high-density lipoproteins (HDL) to in
      vitro oxidation induced by gamma-radiolysis of water.
AB  - In the present study, we investigated the age-related susceptibility of high
      density lipoproteins (HDL) to oxidation. HDL were obtained from healthy,
      normolipidemic young, middle-aged and elderly subjects. Oxidation of HDL was
      induced in vitro by oxygen free radicals generated by water gamma-radiolysis, and
      followed by the decrease of endogenous vitamin E and the formation of conjugated
      dienes and thiobarbituric acid-reactive substances, as well as the alterations of
      apolipoproteins A-I/A-II. The resistance of HDL to oxidation, evaluated by the
      length of the lag phase, decreased with aging. This increased oxidizability of
      HDL with aging could have a dramatic impact on the development of atherosclerosis
      in the elderly population.

PMID- 9762899
TI  - Novel defensin subfamily from spinach (Spinacia oleracea).
AB  - Antimicrobial peptides (So-D1-7) were isolated from a crude cell wall preparation
      from spinach leaves (Spinacia oleracea cv. Matador) and, judged from their amino
      acid sequences, six of them (So-D2-7) represented a novel structural subfamily of
      plant defensins (group IV). Group-IV defensins were also functionally distinct
      from those of groups I-III. They were active at concentrations < 20 microM
      against Gram-positive (Clavibacter michiganensis) and Gram-negative (Ralstonia
      solanacearum) bacterial pathogens, as well as against fungi, such as Fusarium
      culmorum, F. solani, Bipolaris maydis, and Colletotrichum lagenarium. Fungal
      inhibition occurred without hyphal branching. Group-IV defensins were
      preferentially distributed in the epidermal cell layer of leaves and in the
      subepidermal region of stems.

PMID- 9762900
TI  - The mystery of the trichothecene 3-O-acetyltransferase gene. Analysis of the
      region around Tri101 and characterization of its homologue from Fusarium
      sporotrichioides.
AB  - The trichothecene 3-O-acetyltransferase gene, Tri101, plays a pivotal role for
      the well-being of the type B trichothecene producer Fusarium graminearum. We have
      analyzed the cosmids containing Tri101 and found that this resistance gene is not
      in the biosynthetic gene cluster reported so far. It was located between the UTP
      ammonia ligase gene and the phosphate permease gene which are not related to
      trichothecene biosynthesis. These two 'house-keeping' genes were also linked in
      Fusarium species that do not produce trichothecenes. The result suggests that the
      isolated occurrence of Tri101 is attributed to horizontal gene transfer and not
      to the reciprocal translocation of the chromosome containing the gene cluster.
      Interestingly, 3-O-acetylation was not always a primary self-defensive strategy
      for all the t-type trichothecene producers; i.e. the type A trichothecene
      producer Fusarium sporotrichioides did not acetylate T-2 toxin in vivo although
      the fungus possessed a functional 3-O-acetyltransferase gene. Thus Tri101 appears
      to be a defense option which the producers have independently acquired in
      addition to their original resistance mechanisms.

PMID- 9762901
TI  - Inhibition of glycosaminoglycan modification of perlecan domain I by site
      directed mutagenesis changes protease sensitivity and laminin-1 binding activity.
AB  - Glycosaminoglycan attachment to perlecan domain I (173 residues) was completely
      prevented by site-directed mutagenesis of Ser-65, Ser-71 and Ser-76 as shown by
      recombinant production in mammalian cells. This did not interfere with the proper
      folding of the domain's SEA module but enhanced its sensitivity to neutral
      proteases. Lack of substitution also abolished binding to the two major heparin
      binding sites of laminin-1.

PMID- 9762902
TI  - Isolation, characterization and synthesis of a novel paradaxin isoform.
AB  - We report the isolation of a novel pardaxin isoform from the toxic secretion of
      the Red Sea Moses sole (Pardachirus marmoratus). Mass spectrometrical analysis of
      the newly purified peptide revealed a different primary structure compared to the
      previously known pardaxin isoforms. Sequence analysis disclosed an aspartic acid
      residue instead of glycine at position 31 of the new isoform. According to the
      novel sequence, a synthetic Asp-31-peptide was compared with the native compound
      as well as with synthetic Gly-31-pardaxin. The isolated Asp-31-pardaxin isoform
      and its synthetic analog exhibited identical elution properties during reverse
      phase HPLC, as well as similar dose-dependent lytic effects on human erythrocytes
      at a concentration of 10(-6) to 10(-5)M. The hemolytic activity of Asp-31
      pardaxins was lower than that of Gly-31-pardaxin and no synergistic effect
      between these peptides was found. The additional negative charge introduced by
      Asp-31 is likely to affect the selectivity of pardaxin pores towards a variety of
      ions.

PMID- 9762903
TI  - ATP-dependent copper transport by the Menkes protein in membrane vesicles
      isolated from cultured Chinese hamster ovary cells.
AB  - The Menkes (MNK) protein is a vital component of copper homeostasis in mammalian
      cells. In this paper we provide the first biochemical evidence that the MNK
      protein functions as a copper-translocating P-type ATPase in mammalian cells. The
      enzyme activity in membrane vesicles prepared from Chinese hamster ovary cells
      overexpressing MNK was ATP-dependent, correlated with the amount of MNK and
      followed Michaelis-Menten kinetics with respect to copper. The copper transport
      was observed only under reducing conditions suggesting MNK transports Cu(I). This
      study opens the way to detailed structure-function studies and assessment of
      functional MNK derived from patients with Menkes disease.

PMID- 9762904
TI  - Mitochondrial Hsp70 cannot replace BiP in driving protein translocation into the
      yeast endoplasmic reticulum.
AB  - To determine whether mitochondrial hsp70 (mHsp70) could substitute for the
      endoplasmic retuculum (ER) Hsp70 (BiP) during protein translocation, we assembled
      ER-derived reconstituted proteoliposomes supplemented with either protein. We
      found that only BiP restored translocation in kar2 mutant vesicles and stimulated
      translocation approximately 3-fold in wild type proteoliposomes. mHsp70
      associated poorly with both a BiP binding (DnaJ) domain of Sec63p and an ER
      precursor, and its ATPase activity was poorly enhanced upon incubation with the
      DnaJ domain. In contrast, BiP bound to the Sec63p-DnaJ domain in an ATP-dependent
      manner and its ATPase activity was stimulated significantly by this polypeptide.
      We conclude that mHsp70 is unable to support protein translocation into the ER
      because it fails to associate productively with Sec63p and a precursor.

PMID- 9762905
TI  - Effect of CRF and related peptides on calcium signaling in human and rodent
      melanoma cells.
AB  - Corticotropin releasing factor (CRF) induces a rapid, within seconds, and dose
      dependent increase in the intracellular Ca2+ in both human and hamster melanoma
      cells. This effect is inhibited by depletion of extracellular calcium using 3 mM
      EGTA and is attenuated by the CRF receptor antagonist, alpha-helical-CRF(9-41).
      Other peptides of the CRF superfamily, sauvagine and urocortin, also induce
      increases in cytoplasmic calcium concentration but at higher concentrations than
      CRF. We conclude that malignant melanocytes express CRF receptors, which are
      coupled to activation of plasma membrane calcium channels.

PMID- 9762906
TI  - Structure of the human transcription factor TFIIF revealed by limited proteolysis
      with trypsin.
AB  - In this study, the human general transcription factor IIF (TFIIF), a heteromeric
      complex of RAP74 and RAP30 subunits, was subjected to limited proteolysis with
      trypsin. The central region of RAP74 was demonstrated to be highly sensitive to
      trypsin while both the N- and C-terminal regions contained trypsin-resistant
      structures. In contrast, RAP30 digestion occurred after proteolysis of RAP74. The
      digestion pattern of RAP74 recruited into the preinitiation complex showed no
      marked difference from that of IIF, while RAP30 in the complex was protected from
      trypsin. These results indicate that RAP74 apparently contains three structural
      domains, the central one of which is externally surfaced and unstructured, but
      RAP30 is internally wrapped by RAP74. Furthermore, the accessibility of the
      central region of RAP74 is unaltered in the minimal preinitiation complex, while
      RAP30 is involved in promoter recognition through its DNA binding activity.

PMID- 9762907
TI  - Okadaic acid-induced apoptosis of HL60 leukemia cells is preceded by
      destabilization of bcl-2 mRNA and downregulation of bcl-2 protein.
AB  - We have studied the actions of the protein phosphatase inhibitor okadaic acid
      (OA) on the expression of bcl-2 in HL60 human leukemia cells. OA induced
      downregulation of bcl-2 mRNA and protein prior to the induction of apoptosis.
      Downregulation of bcl-2 mRNA levels did not result from actions of OA on the bcl
      2 upstream negative response element. Nuclear run-off analyses confirmed that OA
      did not affect bcl-2 gene transcription. However, OA caused a rapid increase in
      the rate of degradation of bcl-2 mRNA. Therefore, OA induces down-regulation of
      bcl-2 expression via destabilization of its transcript. The constitutive action
      of an OA-sensitive protein phosphatase may therefore maintain HL60 cell survival
      by blocking bcl-2 mRNA degradation.

PMID- 9762908
TI  - A second isoform of gonadotropin-releasing hormone is present in the brain of
      human and rodents.
AB  - Gonadotropin-releasing hormone-I (GnRH-I), present in the mammalian hypothalamus,
      regulates reproduction. In this study we demonstrate, for the first time, that an
      additional isoform of GnRH, [His5, Trp7, Tyr8] GnRH-I (GnRH-II) is present in the
      brain of the mouse, rat and human. Human and rat brain extracts contain two
      isoforms of GnRH, GnRH-I and GnRH-II, which exhibited identical chromatographic
      properties to the respective synthetic peptides, in high performance liquid
      chromatography. Using immunohistochemical techniques we have found that GnRH-II
      is present in neuronal cells that are localized mainly in the periaqueductal area
      as well as in the oculomotor and red nuclei of the midbrain. It is of interest to
      note that in the hypogonadal mouse, although the GnRH-I gene is deleted, GnRH-II
      is present. Substantial concentrations of GnRH-II are also present in the
      hypothalamus and stored in the human pituitary stalk or in the mouse median
      eminence. By using reverse transcription (RT)-PCR we have also found that while
      GnRH-II is not expressed in the cerebellum, it is expressed in all three
      structures of the brain stem: midbrain, pons and medulla oblongata.

PMID- 9762909
TI  - cDNA cloning of Brassica napus malonyl-CoA:ACP transacylase (MCAT) (fab D) and
      complementation of an E. coli MCAT mutant.
AB  - The GenBank database was searched using the E. coli malonyl CoA:ACP transacylase
      (MCAT) sequence, for plant protein/cDNA sequences corresponding to MCAT, a
      component of plant fatty acid synthetase (FAS), for which the plant cDNA has not
      been isolated. A 272-bp Zea mays EST sequence (GenBank accession number:
      AA030706) was identified which has strong homology to the E. coli MCAT. A PCR
      derived cDNA probe from Zea mays was used to screen a Brassica napus (rape) cDNA
      library. This resulted in the isolation of a 1200-bp cDNA clone which encodes an
      open reading frame corresponding to a protein of 351 amino acids. The protein
      shows 47% homology to the E. coli MCAT amino acid sequence in the coding region
      for the mature protein. Expression of a plasmid (pMCATrap2) containing the plant
      cDNA sequence in Fab D89, an E. coli mutant, in MCAT activity restores growth
      demonstrating functional complementation and direct function of the cloned cDNA.
      This is the first functional evidence supporting the identification of a plant
      cDNA for MCAT.

PMID- 9762910
TI  - Growth factor protection against cytokine-induced apoptosis in neonatal rat
      islets of Langerhans: role of Fas.
AB  - Treatment of neonatal rat islets of Langerhans with combined cytokines
      (interleukin-1beta 10(-10) M, tumour necrosis factor-alpha 10(-10) M, interferon
      gamma 5 U/ml) led to extensive cell death, which was potentiated by Fas
      activation with the anti-Fas cytolytic antibody JO2. Pre-treatment with insulin
      (25 ng/ml) or insulin-like growth factor-1 (10(-8)M) gave only partial protection
      against cell killing, but prevented the Fas-mediated component. In the absence of
      cytokine treatment, Fas-mediated killing was not observed.

PMID- 9762912
TI  - Fatty acids as natural uncouplers preventing generation of O2.- and H2O2 by
      mitochondria in the resting state.
AB  - Both natural (laurate) and artificial (m-chlorocarbonylcyanide phenylhydrazone;
      CCCP) uncouplers strongly inhibit O2.- and H2O2 formation by rat heart
      mitochondria oxidizing succinate. Carboxyatractylate, an ATP/ADP antiporter
      inhibitor, abolishes the laurate inhibition, the CCCP inhibition being
      unaffected. Atractylate partially releases the inhibition by laurate and
      decelerates the releasing effect of carboxyatractylate. GDP is much less
      effective than carboxyatractylate in releasing the laurate inhibition of reactive
      oxygen species (ROS) formation. Micromolar laurate concentrations arresting the
      ROS formation cause strong inhibition of reverse electron transfer from succinate
      to NAD+, whereas State 4 respiration and the transmembrane electric potential
      difference (delta psi) level are affected only slightly. It is suggested that (i)
      free fatty acids operate as natural 'mild uncouplers' preventing the
      transmembrane electrochemical H+ potential difference (delta muH+) from being
      above a threshold critical for ROS formation by complex I and, to a lesser
      degree, by complex III of the respiratory chain, and (ii) it is the ATP/ADP
      antiporter, rather than uncoupling protein 2, that is mainly involved in this
      antioxidant mechanism of heart muscle mitochondria.

PMID- 9762911
TI  - The effects of SNAP/SNARE complexes on the ATPase of NSF.
AB  - The ATPase of the N-ethylmaleimide sensitive factor (NSF) appears to be central
      to the events that culminate in vesicle-target membrane fusion. Complexes
      containing different combinations of NSF, alpha-SNAP, Vamp-2 (synaptobrevin 2),
      syntaxin 1, and SNAP-25 were reconstituted and then tested for their effect on
      the ATPase of NSF. While NSF interacts with all alpha-SNAP-containing complexes,
      only the alpha-SNAP/t-SNARE complex significantly stimulated ATPase activity.
      This stimulation was dependent on increasing SNAP/t-SNARE complex and was
      saturable. The apparent stimulation of ATPase activity is due to a 10-fold
      increase in initial hydrolysis rate. Complex containing both v- and t-SNAREs
      bound significantly more alpha-SNAP but did not stimulate the ATPase of NSF.

PMID- 9762914
TI  - Intestinal lactase-phlorizin hydrolase (LPH): the two catalytic sites; the role
      of the pancreas in pro-LPH maturation.
AB  - Brush border lactase-phlorizin hydrolase carries two catalytic sites. In the
      human enzyme lactase comprises Glu-1749, phlorizin hydrolase Glu-1273. The
      proteolytic processing of pro-lactase-phlorizin hydrolase by (rat) enterocytes
      stops two amino acid residues short of the N-terminus of 'mature' final, brush
      border lactase-phlorizin hydrolase. Only these two amino acid residues are
      removed by luminal pancreatic protease(s), probably trypsin.

PMID- 9762913
TI  - Enthalpy of captopril-angiotensin I-converting enzyme binding.
AB  - High-sensitivity titration calorimetry is used to measure changes in enthalpy,
      heat capacity and protonation for the binding of captopril to the angiotensin I
      converting enzyme (ACE; EC 3.4.15.1). The affinity of ACE to captopril is high
      and changes slightly with the pH, because the number of protons linked to binding
      is low. The determination of the enthalpy change at different pH values suggests
      that the protonated group in the captopril-ACE complex exhibits a heat
      protonation of approximately -30 kJ/mol. This value agrees with the protonation
      of an imidazole group. The residues which may become protonated in the complex
      could be two histidines existing in two active sites, which are joined to the
      amino acids coordinated to Zn2+. Calorimetric measurements indicate that
      captopril binds to two sites in the monomer of ACE, this binding being
      enthalpically unfavorable and being dominated by a large positive entropy change.
      Thus, binding is favored by both electrostatic and hydrophobic interactions. The
      temperature dependence of the free energy of binding deltaG degrees is weak
      because of the enthalpy-entropy compensation caused by a large heat capacity
      change, deltaCp =-4.3+/-0.1 kJ/K/mol of monomeric ACE. The strong favorable
      binding entropy and the negative deltaCp indicate both a large contribution to
      binding due to hydrophobic effects, which seem to originate from dehydration of
      the ligand-protein interface, and slight conformational changes in the vicinity
      of the active sites.

PMID- 9762915
TI  - Effects of a time-varying strong magnetic field on transient increase in
      cytosolic free Ca2+ induced by bradykinin in cultured bovine adrenal chromaffin
      cells.
AB  - We tested the effects of exposure to a time-varying magnetic field changing
      between 0.07 and 1.7 T at an interval of 3 s on transient increase in
      intracellular Ca2+ stimulated by bradykinin in bovine adrenal chromaffin cells.
      Addition of bradykinin induced the increase in intracellular Ca2+ within a few
      minutes. The exposure to the magnetic field perfectly suppressed the increase in
      intracellular Ca2+ in Ca2+-free medium. The inhibition occurred for 15 min when
      the maximum magnetic flux density was more than 1.4 T. These results suggest that
      the exposure inhibits Ca2+ release from intracellular Ca2+ stores.

PMID- 9762916
TI  - Activation of caspase-3-like protease by digitonin-treated lysosomes.
AB  - Apoptosis, a naturally occurring programmed cell death or cell 'suicide', has
      been paid much attention as one of the critical mechanisms for morphogenesis and
      tissue remodeling. Activation of cysteine aspartases (caspases) is one of the
      critical steps leading to apoptosis. Although a mitochondria-mediated pathway has
      been postulated to be one of the activation mechanism of caspase-3, another
      subcellular compartment might be involved in the activation of the enzyme. The
      present study shows that the supernatant fraction of digitonin-treated lysosomes
      strongly activates Ac-DEVD-CHO inhibitable caspase-3-like protease. Activation of
      caspase-3-like protease by digitonin-treated lysosomal fractions was specifically
      suppressed by leupeptin and E-64, inhibitors of cysteine protease. These results
      indicate that leakage of lysosomal cysteine protease(s) into the cytosolic
      compartment might be involved in the activation of caspase-3-like protease.

PMID- 9762917
TI  - NSF is required for the brefeldin A-promoted disassembly of the Golgi apparatus.
AB  - N-Ethylmaleimide-sensitive factor (NSF) is required for multiple pathways of
      vesicle-mediated protein transport. Microinjection of a monoclonal anti-NSF
      antibody almost completely blocked brefeldin A-promoted Golgi disassembly without
      affecting the rapid release of beta-COP, a subunit of the Golgi coat proteins
      (COPI), from the Golgi apparatus. Similar results were obtained using a dominant
      negative NSF which is known to compete with endogenous NSF. The present results
      suggest that an NSF-mediated step is present in the brefeldin A-promoted
      disassembly of the Golgi apparatus.

PMID- 9762918
TI  - The Pzh1 protein phosphatase and the Spm1 protein kinase are involved in the
      regulation of the plasma membrane H+-ATPase in fission yeast.
AB  - We have previously shown that the mutation of the Schizosaccharomyces pombe PPZ
      like protein phosphatase encoded by the gene pzh1+ results in increased tolerance
      to sodium and in hypersensitivity to potassium ions. A similar phenotype has also
      been reported for deletants in the spm1/pmk1 gene, encoding a mitogen-activated
      protein (MAP) kinase. We have found that the sodium tolerance phenotype of pzh1
      deletants is stronger than that of spm1 mutants, and both effects are additive.
      Therefore, most probably both gene products mediate different pathways on sodium
      tolerance. In our hands, mutation of the kinase does not alter the tolerance to
      potassium, but it yields cells more tolerant to magnesium ions. While in budding
      yeast the mutations are synthetically lethal, fission yeast cells lacking both
      the phosphatase and the kinase genes are viable. Interestingly, their ability to
      export H+ to the medium is greatly impaired (although not that of pzh1 or spm1
      single mutants). We have observed that, although the amount of the H+-ATPase in
      the plasma membrane is not altered, the activity of the enzyme is lower than
      normal and cannot be induced by glucose. These observations suggest that the
      activity of the H+-ATPase in fission yeast might be regulated by phospho
      dephosphorylation mechanisms that might involve the pzh1+ and spm1+ gene
      products.

PMID- 9762919
TI  - Heterologous expression of human H1 histones in yeast.
AB  - The complete set of seven human H1 histone subtype genes was heterologously
      expressed in yeast. Since Saccharomyces cerevisiae lacks standard histone H1 we
      could isolate each recombinantly expressed human H1 subtype in pure form without
      contamination by endogenous H I histones. For isolation of the H1 histones in
      this expression system no tagging was needed and the isoforms could be extracted
      with the authentic primary structure by a single extraction step with 5%(0.74 M)
      perchloric acid. The isolated H1 histone proteins were used to assign the subtype
      genes to the corresponding protein spots or peaks after two-dimensional gel
      electrophoresis and capillary zone electrophoresis, respectively. This allowed us
      to correlate transcriptional data with protein data, which was barely possible
      until now.

PMID- 9762920
TI  - Two distinct classes of rat intestinal mucosal enzymes incorporating putrescine
      into protein.
AB  - Tissue-transglutaminase (t-TGase) is a family of calcium-dependent enzymes. A
      Ca2+-independent soluble enzyme, in addition to t-TGase, capable of incorporating
      polyamines into proteins was demonstrated in rat intestinal mucosa. The Ca2+
      independent enzyme was stimulated 2- to 5-fold by Fe2+ and Co2+ ions but
      inhibited by Cu2+ and Zn2+ ions. The Ca2+-stimulated t-TGase activity was
      inhibited by divalent ions in the following order: Zn2+, Fe2+ >Co2+ > Cu2+. The
      opposite effects of EGTA, Fe2+ and Co2+ on these two enzyme activities indicate
      that they are two distinct classes of enzymes. Competition studies demonstrated
      differential preferences of the two enzymes for substrates. The Ca2+-dependent
      enzyme preferred putrescine, monodansylcadaverine > cadaverine, spermidine,
      spermine > 1,10-diaminodecane > triethylbutylamine. On the other hand, the Ca2+
      independent enzyme preferred putrescine > cadaverine > spermine, I,10
      diaminodecane > spermidine > monodansylcadaverine > triethylbutylamine. Further
      studies with divalent ions excluded the possible association of this novel Ca2+
      independent enzyme with diamine oxidase. Finally, the Ca2+-independent enzyme had
      a higher affinity for putrescine (Km = 0.02 mM) than did Ca2+-dependent t-TGase
      (0.2 mM). As judged by gel filtration on HiPrep Sephacryl 200 column, the Ca2+
      independent enzyme had a molecular weight of approximately 48 kDa, the intestinal
      Ca2+-dependent t-TGase was about 188 kDa while that of testicular t-TGase was
      about 96 kDa. In conclusion, the Ca2+-independent enzyme is stimulated by cobalt
      or ferric ions, and selectively incorporates aliphatic diamines or polyamines
      with symmetric amino groups. The observed Ca2+-independent enzyme activity is not
      related to diamine oxidase or its products. With a 10 times greater affinity for
      putrescine, the calcium-independent, 48-kDa intestinal enzyme may mediate
      polyamine function better than calcium dependent, 188-kDa intestinal tissue
      transglutaminase in the intestinal mucosa.

PMID- 9762921
TI  - NMDA-receptor antagonist requirements in conantokin-G.
AB  - A series of variants of the neuroactive 17-residue gamma-carboxyglutamate-(Gla)
      containing polypeptide, conantokin-G (con-G), were synthesized with the intention
      of determining those features that were important for its N-methyl-D-aspartate
      (NMDA) receptor-targeted antagonist activity and for adoption of its divalent
      cation-dependent alpha-helical conformation. Employing the binding of
      [3H]dizolcipine (MK-801) as an assay for open receptor ion channels in rat brain
      membranes, which displays inhibition by con-G (IC50 = 0.48 microM), it was found
      that replacement by an Ala residue of Gla4 led to complete inactivation of the
      peptide, whereas a similar replacement of Gla3 resulted in a 20-fold decreased
      potency. Ala substitutions for Gla10 and Gla14 did not substantially affect
      [3H]MK-801 binding. This same substitution at Gla7 appeared to slightly enhance
      binding. Ala replacements of non-Gla residues demonstrated that four of them,
      viz. Glu2, Leu5, Gln9, and Ile12, possessed at least 200-fold decreases in
      inhibitory potency, whereas similar replacements at Gly1, Leu11, and Arg13
      resulted in peptides with 8- to 12-fold increases in the IC50 values. The
      remaining amino acid residues tested in the single Ala replacement series showed
      no significant changes in the inhibitory characteristics of wild-type con-G.
      Additional studies with carboxyl-terminal truncated peptides revealed that the
      carboxyl-terminal 4 amino acids were unimportant for this activity. There was no
      strict correlation of inhibition of [3H]MK-801 binding with the ability of these
      peptides to form cation-dependent alpha-helices. Peptides with notably low alpha
      helical content in the presence of these cations were lacking at least one, or
      both, of Gla10 and Gla14. Con-G[Gla3,4,7,10,14E] and con-G[Gla7,10,14E] were the
      only peptides that remained in a completely random conformation upon metal ion
      addition.

PMID- 9762922
TI  - Cloning, expression, and localization of a novel gamma-adaptin-like molecule.
AB  - We describe the cloning, expression, and localization of gamma2-adaptin, a novel
      isoform of gamma-adaptin. The predicted human and mouse gamma2-adaptin proteins
      are approximately 90 kDa and 64.4% and 61.7%) identical to gamma-adaptin,
      respectively. gamma2-Adaptin was localized to the Golgi, its localization
      distinct from gamma-adaptin. The membrane association of gamma- and gamma2
      adaptin could further be distinguished by differential sensitivity to the fungal
      metabolite brefeldin A, gamma2-adaptin binding being insensitive to drug
      treatment. Together, these results suggest that gamma2-adaptin plays a role in
      membrane transport distinct from that played by gamma-adaptin.

PMID- 9762923
TI  - Membrane potential generation coupled to oxidation of external NADH in liver
      mitochondria.
AB  - Oxidation of added NADH by rat liver mitochondria has been studied. It is found
      that exogenous NADH, when oxidized by rat liver mitochondria in sucrose hypotonic
      medium supplemented with Mg2+ and EGTA, generates a membrane potential (delta
      psi) even in the absence of added cytochrome c. ADP and phosphate decrease delta
      psi, the effect being reversed by oligomycin. Rotenone and myxothiazol do not
      inhibit delta psi generated by oxidation of exogenous NADH. Added cytochrome c
      increases the rate of the exogenous NADH oxidation and coupled delta psi
      formation. In sucrose isotonic medium, or in hypotonic medium without Mg2+,
      exogenous NADH fails to stimulate respiration and to form a membrane potential.
      In the presence of Mg2+, exogenous NADH appears to be effective in delta psi
      generation in isotonic sucrose medium if mitochondria were treated with
      digitonin. In isotonic KCl without Mg2+, oxidation of exogenous NADH is coupled
      to the delta psi formation and MgCl2 addition before mitochondria prevents this
      effect. In hypotonic (but not in isotonic) sucrose medium, Mg2+ makes a portion
      of the cytochrome c pool reducible by exogenous NADH or ascorbate. It is assumed
      that (i) hypotonic treatment or digitonin causes disruption of the outer
      mitochondrial membrane, and, as a consequence, desorption of the membrane-bound
      cytochrome c in a Mg2+-dependent fashion; (ii) incubation in isotonic KCI without
      Mg2+ results in swelling of mitochondrial matrix, disruption of the outer
      membrane and cytochrome c desorption whereas Mg2+ lowers the K+ permeability of
      the inner membrane and, hence, prevents swelling; (iii) desorbed cytochrome c is
      reduced by added NADH via NADH-cytochrome b5 reductase and cytochrome b5 or by
      ascorbate and is oxidized by cytochrome oxidase. The role of desorbed cytochrome
      c in oxidation of superoxide and cytoplasmic NADH as well as possible relations
      of these events to apoptosis are discussed.

PMID- 9762924
TI  - Identification of a dynein molecular motor component in Torpedo electroplax;
      binding and phosphorylation of Tctex-1 by Fyn.
AB  - The microtubule protein Tctex-1 was cloned from Torpedo electroplax, a
      biochemical model of the neuromuscular junction, using the unique domain of Fyn
      in the yeast two hybrid system. Binding of Tctex-1 and Fyn also occurred in
      vitro. Torpedo Tctex-1 was contained within the molecular motor protein dynein. A
      Src class kinase was also complexed with dynein. Tctex-1 was enriched in electric
      organ vs. skeletal muscle, was present in the postsynaptic membrane, and
      coprecipitated with the acetylcholine receptor. The sequence of Tctex-1 contained
      a tyrosine phosphorylation motif and Tctex-1 could be phosphorylated by Fyn in
      vitro and in vivo. These data demonstrated that Tctex-1-containing dynein is a
      cytoskeletal element at the acetylcholine receptor-enriched postsynaptic membrane
      and suggested that Tctex-1 may be a substrate for Fyn.

PMID- 9762925
TI  - Cancer epidemiology 50 years later.

PMID- 9762926
TI  - Can cancer risks be altered by changing nutritional traditions?

PMID- 9762927
TI  - Cancer surveillance in the U.S.: can we have a national system?
AB  - Cancer-related services are consuming ever-increasing health resources; along
      with this trend, health care costs are rising. As health care planners,
      researchers, and policymakers formulate strategies to meet this challenge, they
      are looking to cancer registries and the health information system built around
      them as collectors of the most extensive information regarding cancer treatment
      in the U.S. Currently, there are multiple programs collecting and reporting data
      regarding cancer incidence, morbidity, mortality, and survival. This report
      profiles cancer surveillance efforts in the U.S. and describes the National
      Coordinating Council for Cancer Surveillance, which was organized in 1995 to
      facilitate a collaborative approach among the organizations involved.

PMID- 9762929
TI  - Immunohistochemical evaluation of thymidylate synthase in gastric carcinoma using
      a new polyclonal antibody: the clinical role of thymidylate synthase as a
      prognostic indicator and its therapeutic usefulness.
AB  - BACKGROUND: Before this study was conducted, the clinical and therapeutic
      significance of immunohistochemical evaluation of thymidylate synthase (TS) in
      patients with gastric carcinoma had not yet been clarified. METHODS: TS was
      immunohistochemically evaluated in 134 gastric carcinomas using anti-TS antibody.
      TS expression, 11 clinicopathologic variables, and survival were studied, and the
      correlations among them were investigated. RESULTS: The groups with high and low
      TS levels consisted of 56 and 78 patients, respectively. Granular cytoplasmic
      staining patterns of tumor cells were produced by immunohistochemical staining of
      the gastric carcinoma tissues. The grade of TS staining was significantly
      correlated with three clinicopathologic variables: depth of invasion, peritoneal
      metastasis, and stage of the carcinoma (P < 0.05). A univariate analysis revealed
      that the 5-year survival was significantly better for the low TS group than for
      the high TS group (P < 0.05): 65.2% for the low TS group and 43.2% for the high
      TS group. The group with high grade TS staining who received chemotherapy because
      of the advanced stage of their disease had worse prognoses even if they received
      adjuvant chemotherapy. A multivariate analysis revealed that four variables
      (peritoneal metastasis, lymphatic invasion, liver metastasis, and TS staining
      grade) independently contributed to survival (P < 0.05). The hazard ratio for the
      group with low grade TS staining was 0.464 compared with the group with high
      grade staining. CONCLUSIONS: The immunohistochemical evaluation of TS using this
      anti-TS antibody may be clinically and therapeutically useful in determining the
      prognosis of gastric carcinoma patients.

PMID- 9762928
TI  - Salivary gland malignant myoepithelioma: a clinicopathologic and
      immunohistochemical study of ten cases.
AB  - BACKGROUND: Malignant myoepithelioma (MME) of the salivary gland, also known as
      myoepithelial carcinoma, is rare and its biologic behavior has not been clarified
      fully. METHODS: Ten cases of MME were analyzed for their clinicopathologic
      features and immunohistochemical characteristics, focusing on prognostic factors
      and tumor differentiation. In addition, six cases of benign myoepithelioma (BME)
      also were examined for comparison. RESULTS: The ten patients with MME (3 men and
      7 women) ranged in age from 48-81 years (mean, 61.9 years). Seven cases of MME
      arose in the parotid salivary gland, two in the submandibular salivary gland, and
      one in minor salivary glands of the soft palate. In the current series, the
      incidence of MME was 0.45% among 1945 cases of major salivary gland tumors. Seven
      cases of MME developed from a benign preexisting tumor (six in pleomorphic
      adenoma and one in BME). Four of nine patients with MME died of the disease and
      two patients developed a recurrence. It was shown that MMEs were comprised of one
      cell type or a combination of two cell populations; these included, in order of
      incidence, epithelioid, spindle, and plasmacytoid cells. Patients with MME with
      marked cellular pleomorphism and perineural invasion had a poor prognosis.
      Immunohistochemically, putative myoepithelial markers such as muscle actins,
      cytokeratin 14, vimentin, and calponin, and S-100 protein were expressed highly
      in MME. High and low molecular weight cytokeratins and epithelial membrane
      antigen also frequently were positive in MME. p53 expression was observed in five
      MME cases, four of which either recurred or were fatal. Cellular proliferative
      activity assessed by mitotic count and the Ki-67 labeling index was significantly
      higher in MME cases than in BME cases. In limited cases, such cellular
      proliferative activity was shown to have prognostic value. Ultrastructurally, the
      tumor cells displayed certain myoepithelial characteristics. CONCLUSIONS: MME is
      a rare salivary gland tumor showing clinicopathologic diversity and presenting
      with various stages of myoepithelial differentiation. Histologic aggressiveness,
      marked cellular pleomorphism, p53 expression, and high cell proliferative
      activity were found to be correlated with a poor clinical outcome.

PMID- 9762930
TI  - Multifocal occurrence of gastric carcinoma in patients with a family history of
      gastric carcinoma.
AB  - BACKGROUND: Smoking and alcoholic beverage drinking habits as well as a family
      history of cancer are well known risk factors for the multifocal occurrence of
      squamous cell carcinoma of the esophagus and the head and neck region. However,
      the role of these risk factors in multiple gastric carcinoma remains to be
      clarified. The purpose of this study was to examine the risk factors for multiple
      gastric carcinoma. METHODS: The smoking and drinking habits as well as the family
      history of 157 patients with synchronous multiple gastric carcinoma and 157
      patients with solitary gastric carcinoma who were similar with regard to gender,
      age, stage of the tumor, and year of admission were investigated. The risk of a
      multiple occurrence of gastric carcinoma also was elevated using the odds ratio
      (OR). RESULTS: The ORs of a multifocal occurrence of gastric carcinoma in
      patients who currently smoked and drank alcoholic beverages were 1.1 and 0.8,
      respectively, although the ORs were not related to the quantity of smoking or
      drinking. In patients with a close relative with gastric carcinoma the OR was 2.1
      (95% confidence interval [CI], 1.3-3.7). In those patients with > or =2 close
      relatives with gastric carcinoma, the OR increased to 5.1 (95% CI, 1.2-21.1).
      Conversely, no significant elevation in the ORs was recognized regarding a family
      history of other cancers. CONCLUSIONS: In this study, a family history of gastric
      carcinoma was found to be clearly associated with the multifocal occurrence of
      gastric carcinoma; however, no significant correlation between the multifocal
      occurrence of gastric carcinoma in these patients and their smoking and drinking
      habits was recognized.

PMID- 9762931
TI  - A clinicopathologic study of mucinous gastric carcinoma including multivariate
      analysis.
AB  - BACKGROUND: Mucinous gastric carcinoma (MGC) is a rare subtype of gastric
      adenocarcinoma, and its clinical and pathologic features are still controversial.
      To clarify the significance of this subtype of carcinoma, the authors conducted a
      case-control study to investigate the clinicopathologic characteristics of MGC
      and determine whether this mucin-producing histologic type is associated with a
      worse prognosis than other gastric carcinomas. METHODS: Twenty-two cases of MGC
      and 46 patients with nonmucinous gastric carcinoma (NGC) were included. Patients
      were evaluated on the basis of age, gender, tumor size, location, depth of tumor
      invasion, histologic differentiation, lymph node involvement, organ metastasis,
      stage at presentation, surgical curability, adjuvant chemotherapy and radiation
      therapy. To determine whether the MGC itself was an independent prognostic
      factor, a multivariate analysis was performed with the Cox proportional hazards
      model. RESULTS: The MGC patients were found to have larger tumors (P < 0.001),
      tumors more often located in the upper stomach (P < 0.05), more serosal invasion
      (P < 0.05), more lymph node involvement (P < 0.05), greater frequency of advanced
      stage disease (P < 0.01), and lower 5-year survival rates (P < 0.05) than NGC
      patients. There was no significant correlation between the subtypes of
      differentiation of MGC and other data, including the prognosis. Multivariate
      analysis showed that clinically important predictive factors were serosal
      invasion and disease stage at diagnosis. The mucinous histologic type itself was
      not an independent factor for poor prognosis. CONCLUSIONS: The overall survival
      rate for patients with MGC was worse than that for patients with NGC. The poor
      prognosis was correlated with more advanced stage at diagnosis and more frequent
      serosal invasion, not with the mucinous histologic type.

PMID- 9762932
TI  - Rectal epithelial proliferation in persons with or without a history of adenoma
      and its association with diet and lifestyle habits.
AB  - BACKGROUND: Rectal epithelial proliferation (REP) measurements are used as a
      biomarker of risk for colorectal neoplasia and response to chemoprevention. The
      authors evaluated REP in screenees with and without a history of adenoma and its
      association with demographic and adenoma characteristics, diet, and other
      lifestyle habits. METHODS: Long term lifestyle habits were evaluated and
      proliferation assessed by in vitro bromodeoxyuridine labeling of rectal biopsies
      in 223 screenees, 132 of whom had adenomas removed > 3 years previously. Analyses
      included the total population, screenees with a previous history of adenomas and
      adenoma free screenees separately, and a subgroup of 55 matched adenoma cases and
      controls. RESULTS: Crypt proliferation measurements were not elevated in
      screenees with a history of adenomas compared with adenoma free screenees (mean
      total labeling index [LI] of 4.8% and 4.9%, respectively). This was confirmed by
      the case-control analysis, in which the LI of the most superficial crypt
      compartment was lower in the adenoma cases (P=0.05). Moreover, their total LI
      correlated negatively with the number of adenomas removed previously (P < 0.01).
      Proliferation was more frequent in the most superficial crypt compartments of
      female adenoma free screenees than in female screenees with a history of adenomas
      (P=0.02), and in men age > 65 years compared with younger men (P=0.06). In the
      total population, negative Spearman rank correlations were found between total LI
      and long term dietary intake of calcium (correlation coefficient [r]=-0.15;
      P=0.02), LI of the two most superficial crypt compartments and intake of fiber
      (r=-0.18; P=0.01), water (r=-0.12; P=0.08), and carbohydrates (not significant).
      A positive correlation was found between LI of the most superficial crypt
      compartment and cigarette smoking (r=0.4; P=0.02). CONCLUSIONS: REP measurements
      did not discriminate between screenees with a history of adenomas and adenoma
      free screenees. Long-term lifestyle habits, gender, and age were associated with
      REP levels and need to be considered when evaluating human intervention studies.

PMID- 9762933
TI  - Adenocarcinoma of the pancreas: detection of occult metastases in regional lymph
      nodes by a polymerase chain reaction-based assay.
AB  - BACKGROUND: Stage I (T1-2NOM0) adenocarcinoma of the pancreas is associated with
      a 5-year survival rate of 15-25%. Despite apparently curative resection and
      pathologic staging indicating localized disease, these cancers recur. The authors
      hypothesized that there exists microscopic regional disease that is not detected
      by surgical exploration or routine histopathology. METHODS: Because 90-95% of
      pancreatic cancers exhibit codon 12 K-ras mutations, the authors examined
      regional lymph nodes for mutated K-ras as a marker of metastasis. DNA was
      extracted from paraffin embedded archival specimens (primary tumors and
      histologically negative lymph nodes) of patients with Stage I pancreatic
      adenocarcinoma. The target region of K-ras was amplified by polymerase chain
      reaction (PCR) and tested for codon 12 mutation by BstN1 restriction digestion
      (restriction fragment length polymorphism [RFLP]) that recognized normal but not
      mutated sequences. Cell lines that harbored normal or mutated K-ras and resected
      jejunum or gallbladder were used as controls. The regional lymph nodes of 22
      patients whose tumors harbored mutated K-ras were tested. RESULTS: Dilution
      experiments with normal and mutant control cell line DNA demonstrated an assay
      sensitivity for mutated K-ras of 0.1%. Mutated K-ras was found in at least 1
      regional lymph node in 16 (73%) of 22 patients with pathologic Stage I pancreatic
      adenocarcinoma, which suggested metastases not detected by routine
      histopathology. DNA sequence analysis was performed in four patients and
      confirmed identical point mutations in the primary tumor and accompanying
      PCR/RFLP positive lymph nodes. CONCLUSIONS: Pathologic examination of regional
      lymph nodes in pancreatic adenocarcinoma specimens fails to detect metastases in
      many patients. Lymph node micrometastasis is one reason for the poor survival
      rates observed among patients with Stage I cancers. PCR/RFLP may have a role in
      staging early pancreatic cancers.

PMID- 9762934
TI  - Bombesin/gastrin-releasing peptide antagonists RC-3095 and RC-3940-II inhibit
      tumor growth and decrease the levels and mRNA expression of epidermal growth
      factor receptors in H-69 small cell lung carcinoma.
AB  - BACKGROUND: Antagonists of bombesin/gastrin-releasing peptide (BN/GRP) have been
      developed to block the autocrine stimulatory effect of BN/GRP on tumors such as
      small cell lung carcinoma (SCLC). Although several studies have addressed the
      intracellular events that follow the formation of the receptor-ligand complex,
      the mechanism of action of BN/GRP antagonists remains unclear. METHODS: In this
      study the authors investigated the effect of synthetic BN/GRP antagonists RC-3095
      and RC-3940-II on tumor growth and the expression of epidermal growth factor
      receptors (EGF-R) in H-69 SCLC. Athymic nude mice xenografted with H-69 SCLC were
      treated subcutaneously for 5 weeks with RC-3095 and RC-3940-II at the dose of 10
      microg/animal/day. RESULTS: RC-3095 decreased tumor volume by approximately 50%
      (P < 0.05) and RC-3940-II by 70-60% (P < 0.01). Tumor burden also was
      significantly decreased in the groups treated with RC-3095 and RC-3940-II.
      Receptor analyses demonstrated high affinity binding sites for BN/GRP and EGF on
      the untreated H-69 SCLC tumors. After treatment with RC-3095 and RC-3940-II, the
      concentration of receptors for BN/GRP was decreased by 29.0% and 36.5%,
      respectively (both, P < 0.01) compared with controls, and EGF-R levels were
      reduced by 62.3% and 63.0%, respectively (both, P < 0.01). Reverse transcriptase
      polymerase chain reaction and Southern blot analyses revealed that the levels of
      mRNA for EGF-R in tumors were lowered by 31% (P < 0.05) and 43% (P < 0.01),
      respectively, after treatment with RC-3095 and RC-3940-II. CONCLUSIONS: This
      study indicates that the inhibition of growth of H-69 SCLC by BN/GRP antagonists
      RC-3095 and RC-3940-II is accompanied by a marked decrease in the levels and mRNA
      expression of EGF-R.

PMID- 9762935
TI  - Remission induction therapy of untreated acute myeloid leukemia using a non
      cytarabine-containing regimen of idarubicin, etoposide, and carboplatin.
AB  - BACKGROUND: The safety and efficacy of idarubicin, etoposide, and carboplatin as
      remission induction therapy for patients younger than 60 years with untreated
      acute myeloid leukemia was studied as an alternative to standard regimens based
      on cytarabine plus anthracycline. METHODS: Eligible patients received idarubicin
      (36-40 mg/m2), etoposide (500 mg/m2), and carboplatin (1000-1500 mg/m2) over 5
      days. Those who achieved complete remission received a single course of
      cytarabine 1.5 gm/m2 every 12 hours for a total of 12 doses. D-xylose absorption
      was studied as a marker for cytotoxic therapy-induced gut mucosal damage.
      Cytogenetic and immunophenotyping studies were performed at the time of diagnosis
      and examined for prognostic importance. RESULTS: Remission was achieved in 29
      (67%) of 43 patients with a single induction course. The median leukemia free and
      overall survival times were 15.4 months (95% CI 6.5-24.2) and 12.5 months (95% CI
      5.9-19.1), respectively. Induction mortality was 14%. Karyotype (normal, simple,
      or complex vs. very complex) was the strongest predictor of remission (79% vs.
      25%, P=0.01), leukemia free survival (odds ratio [OR] 19.3, 95% CI 2.7-138.9),
      and overall survival (OR 5.4, 95% CI 2.1-13.9). Dose-limiting gut mucosal
      toxicity was greatest during Weeks 2 and 3. Bloodstream infections occurred in
      49% of patients at a median of 12 days. Grade 3-4 diarrhea, nausea, stomatitis,
      esophagitis/dysphagia, and vomiting developed in 33%, 26%, 23%, 9%, and 2% of
      cases, respectively, at a median of 17, 16, 11, 15.5, and 21 days, respectively.
      CONCLUSIONS: This regimen was active in adults younger than 60 years with
      untreated acute myeloid leukemia and normal, simple, or complex karyotypes.
      Remission duration was confounded by karyotype. Mucosal toxicity limited the
      tolerability of this regimen. These adverse effects might be overcome by
      increasing the intensity of postremission therapy and modifying the dosing
      schedule.

PMID- 9762936
TI  - Tumor-associated antigen TA-90 immune complex assay predicts subclinical
      metastasis and survival for patients with early stage melanoma.
AB  - BACKGROUND: TA-90 is a tumor-associated antigen first identified in the urine and
      sera of patients with metastatic melanoma. In the early stages of disease, TA-90
      is present in circulating immune complexes (ICs) that may be detected with an
      antigen specific enzyme-linked immunosorbent assay (ELISA). In this study, the
      authors evaluated the efficacy of the TA-90 IC assay in detecting subclinical
      metastasis of early stage melanoma and predicting the survival of patients with
      this disease. METHODS: Archival sera were collected preoperatively from 114
      patients who underwent wide excision with or without regional lymphadenectomy in
      the treatment of clinical Stage I melanoma. Sera were analyzed for TA-90 IC in a
      blinded fashion, and results were correlated with the patient's clinical course
      as determined by database and chart review. Subclinical metastases were
      considered present at the time of surgery if the lymphadenectomy specimen was
      pathologically positive and/or the patient subsequently developed recurrence.
      RESULTS: The TA-90 IC assay predicted subclinical metastasis in 43 of 56 patients
      (P < 0.0001), with 14 false-positive and 13 false-negative results. Sensitivity
      and specificity for the detection of occult metastasis were 77% and 76%,
      respectively. Positive and negative predictive values were 75% and 77%,
      respectively. Fifteen of 18 tumor positive regional lymph node basins (83%) and
      34 of 46 recurrences (74%) were accurately predicted when considered
      independently (P < 0.004). Preoperative TA-90 IC status was also highly
      correlated with survival: 5-year overall and disease free survival rates were 63%
      and 46%, respectively, for the TA-90 IC positive group, compared with 88% and
      82%, respectively, for the TA-90 IC negative group (P=0.0001). A multivariate
      analysis with standard prognostic variables identified preoperative TA-90 IC
      status as a strong, independent prognostic factor for both overall and disease
      free survival. CONCLUSIONS: To the authors' knowledge, TA-90 is the first tumor
      marker that accurately predicts subclinical metastatic disease and survival for
      patients with early stage melanoma. For this reason, the TA-90 IC assay has the
      potential to improve dramatically the prognostic evaluation of patients with this
      disease. Its role in postoperative risk stratification and early detection of
      recurrence is being evaluated in a prospective study.

PMID- 9762937
TI  - Complications of axillary lymph node dissection for carcinoma of the breast: a
      report based on a patient survey.
AB  - BACKGROUND: Axillary lymph node dissection is commonly performed as part of the
      primary management of breast carcinoma. Its value in patient management, however,
      has recently been questioned. Few studies exist that document long term
      complications. METHODS: Four hundred thirty-two patients with Stage I or II
      breast carcinoma who were free of recurrence 2-5 years after surgery were
      identified. A cross-sectional survey was conducted to determine the prevalence of
      long term symptoms and complications as perceived by the patient, and patient and
      treatment factors that may have predicted complications were determined. Three
      hundred thirty of the 432 (76%) completed a mailed, self-administered
      questionnaire. In addition, the medical records of the 330 patients were
      reviewed. Patient and treatment factors were analyzed with logistic regression.
      RESULTS: Numbness was reported by 35% of patients at the time of the survey. Pain
      was noted in 30%, arm swelling in 15%, and limitation of arm movement in 8%.
      Eight percent reported episodes of infection or inflammation at some point since
      the diagnosis of breast carcinoma. The majority of symptoms were mild and
      interfered minimally with daily activities. Younger age (P=0.001) was associated
      with more frequent reporting of pain. Numbness was more common in younger
      patients (P=0.004) as well as in those with a history of smoking (P=0.012). There
      was a positive association of limitation of arm motion with adjuvant tamoxifen
      therapy (P=0.016). Arm swelling was associated with both younger age (P=0.004)
      and greater body surface area (P=0.008). Radiation therapy was associated with a
      higher frequency of infection or inflammation in the arm and/or breast (P=0.001).
      CONCLUSIONS: Mild symptoms, especially pain and numbness, are common 2-5 years
      after axillary lymph node dissection. The frequency of inflammation or infection
      in patients treated with radiation to the breast or chest wall after an axillary
      lymph node dissection may be greater than previously appreciated. Severe
      complications or symptoms that have a major impact on daily activities are
      uncommon. These findings should help health care providers and their patients
      with breast carcinoma weigh the pros and cons of axillary lymph node dissection.

PMID- 9762938
TI  - A proposed glossary of terminology related to the surgical treatment of vulvar
      carcinoma.
AB  - BACKGROUND: The authors' objective was to provide a glossary of terminology
      related to the surgical treatment of invasive vulvar carcinoma. There is
      currently no consensus in the literature regarding the names of the surgical
      procedures used to treat this disease. METHODS: A surgical glossary should be
      supported by clear definitions and acceptance of notions related to topographic
      anatomy that are specific to the surgical practice. A critical review of the
      classic, chiefly used Italian, French, German, and English textbooks of anatomy
      revealed some discrepancies and lack of uniformity in descriptions of vulvar and
      inguinal fascial structures and lymph nodes, which represent the principal
      landmarks of surgical treatment. In the proposed glossary, the descriptions of
      these anatomic landmarks integrate classic anatomic knowledge, data from recent
      gynecologic studies of inguinal anatomy, and the clinical experiences of the
      authors. RESULTS: The glossary is composed of 16 surgical definitions, which are
      divided into 3 main sections of terminology describing the surgical treatment of
      the: 1) vulva, 2) inguinal lymph nodes, and 3) pelvic lymph nodes. The
      fundamental objective behind the glossary is to describe the area and the depth
      of the surgical procedure. Three determinants of the area (local, partial, and
      total) and three determinants of the depth of surgery (superficial, simple, and
      deep) were used to arrive at the fully articulated definitions in the glossary.
      CONCLUSIONS: The authors are aware that the proposed glossary should not be
      considered a definitive one; however, it could serve as a good basis for further
      debate. The terms employed in the glossary are accompanied by anatomic and
      descriptive references to help avoid confusion and promote better understanding
      among gynecologic oncologists who are involved in the treatment of vulvar
      carcinoma.

PMID- 9762939
TI  - Expression of p150 in cervical neoplasia and its potential value in predicting
      survival.
AB  - BACKGROUND: A recently cloned novel p150 protein was found to be overexpressed in
      human breast carcinoma. To the authors' knowledge, no data on p150 expression in
      any other human tumors have been published previously. METHODS: To investigate
      whether the expression of p150 correlated with the clinicopathologic stages of
      cervical neoplasms or the prognoses of patients with these neoplasms, the authors
      conducted an immunohistochemical study of archival formalin fixed, paraffin
      embedded specimens. Seventy-two precancerous lesions (CIN), 75 clinical Stage IB
      invasive squamous carcinomas, and 20 samples of normal squamous epithelia were
      included. In addition to p150, the Ki-67 labeling index was assessed as a
      proliferation parameter. The presence of human papillomavirus was analyzed by in
      situ DNA hybridization. RESULTS: A significant association of p150 with the grade
      of atypia in cervical neoplasms was demonstrated. The highest expression of p150
      was observed in low grade CIN, with subsequently decreasing expression in high
      grade CIN and invasive carcinoma. For patients with invasive carcinoma, p150 was
      significantly correlated with clinical outcome. Patients with high expression of
      p150 had a better prognosis than those with low p150. Those with regional lymph
      node metastasis and significant p150 expression had longer relapse free survival
      than those with insignificant p150 expression. Women whose carcinomas
      demonstrated vascular space invasion or high microvessel density survived longer
      when p150 was clearly expressed. p150 behaves as a potential tumor marker during
      early cervical carcinoma development and is later turned off as cells proceed to
      more advanced stages of their malignant phenotypes. CONCLUSIONS: p150 is a
      molecular parameter that might become useful in predicting disease progression
      and determining the prognoses of patients with invasive cervical carcinoma.

PMID- 9762940
TI  - Angiogenesis in adenocarcinoma of the uterine cervix.
AB  - BACKGROUND: Angiogenesis is essential for tumor growth, progression, and
      metastases. Microvessel density (MVD), a measure of tumor angiogenesis, has been
      found to have prognostic significance in many tumor types for predicting
      metastasis and survival. METHODS: Between 1979-1989, 56 cases of FIGO Clinical
      Stage I and II adenocarcinoma of the uterine cervix treated by hysterectomy were
      reviewed histologically. All hysterectomy specimens were stained
      immunohistologically for factor VIII-related antigen. MVD was counted in a x200
      field (0.785 mm2 per field) in the most active area of neovascularization.
      Results were expressed as the highest number of microvessels identified within
      any single x200 field. MVD and several other prognostic parameters were examined
      for correlation with progression free survival (PFS) and overall survival (OS) by
      a multivariate analysis according to the Cox proportional hazards model. RESULTS:
      In early adenocarcinoma of the uterine cervix, MVD was increased significantly in
      invasive areas compared with adjacent nonneoplastic areas (median: 62.5 [range,
      30-105] vs. median: 36.5 [range, 23-47]; P=0.0003). MVD also was significantly
      correlated with ascites cytology (P=0.0377). There was no correlation between
      microvessel count and lymph node status, depth of invasion, disease stage, lymph
      vascular space invasion, grade, or parametrial involvement. Patients with high
      MVD (> or=75) had significantly worse PFS and OS than those with low MVD (< 75)
      (log rank test, P=0.0180 and 0.0199, respectively). Multivariate analysis showed
      that MVD correlated significantly and independently with PFS and OS. CONCLUSIONS:
      In adenocarcinoma of the cervix, MVD is an independent prognostic factor for PFS
      and OS.

PMID- 9762941
TI  - Endocrine tumors of the cervix: morphologic assessment, expression of human
      papillomavirus, and evaluation for loss of heterozygosity on 1p,3p, 11q, and 17p.
AB  - BACKGROUND: Cervical endocrine tumors are rare lesions, with a varied diagnostic
      nomenclature. A recent consensus meeting proposed a standardized terminology.
      This study evaluated: 1) applicability of histopathologic guidelines; 2) evidence
      of loss of heterozygosity (LOH) at selected sites; and 3) the presence of human
      papillomavirus (HPV) detected by nonisotopic in situ hybridization (ISH).
      METHODS: Thirty-eight cases (patient age range, 19-88 years; mean, 48 years) were
      retrieved. Outcome data were available for 32 patients. Classification was based
      on architectural and cytologic features. Tissue was available from 15 cases for
      LOH analysis with D3S1234(3p14), D3S1289(3p21), THRB(3p24), TP53(17p13),
      D1S468(1p36), and INT-2(11q13). In ten cases, tissue was analyzed by nonisotopic
      ISH with HPV probes for types 6/11, 16/18, and 31/33. RESULTS: Tumors were
      divided into four groups: small cell carcinoma (SCC) (n=25); large cell
      neuroendocrine carcinoma (LCNC) (n=5); SCC with focal LCNC differentiation (n=3),
      and carcinoid tumor (n=5). Tumors defined as exclusively or predominantly SCC had
      a particularly poor prognosis, with 20 patients dead of disease (<6 years after
      diagnosis) and 6 alive with disease (after <3 years of follow-up). LOH at various
      3p loci (3p14, 3p21, and 3p24) was observed in eight cases. One patient
      demonstrated LOH on 17p(TP53). Eight of ten cases assessed by ISH showed nuclear
      staining using a combined HPV-16/18 probe. CONCLUSIONS: Cervical endocrine tumors
      are highly aggressive and can be subdivided into definable categories. LOH at 3p
      loci is a frequent finding, as is nuclear staining with a combined HPV-16/18
      probe. LOH at 17p(TP53 locus) appears to be relatively uncommon, suggesting that
      p53 mutations may not be developmentally significant.

PMID- 9762942
TI  - Expression of ras, c-myc, and p53 proteins in cervical intraepithelial neoplasia.
AB  - BACKGROUND: The development of cervical carcinoma is influenced by multiple
      factors, including the presence of certain high risk types of human
      papillomavirus. The purpose of the current study was to investigate possible
      cooperating genetic changes by examining the expression of p53, p62 myc, and p21
      ras in cervical biopsy specimens. METHODS: Three hundred and ninety-five cervical
      biopsy specimens representing normal through high grade cervical intraepithelial
      neoplasia (CIN) were screened by immunohistochemistry for expression of p53,
      p62myc, and p21ras. RESULTS: Neither the proportion of tissues staining positive
      for a given protein nor the staining patterns within the epithelial layers
      differed significantly among normal or CIN biopsy samples. However, grade
      specific nuclear staining of p21ras was found in the cells of 10 lesions that
      were classified as CIN I by histology. CONCLUSIONS: These results established the
      normal distribution and expression patterns of p53, p62myc, and p21ras within 395
      cervical biopsy samples representing normal through CIN III histology. The
      expression of these proteins (e.g., staining intensity and layer of epithelium
      staining positive) is similar in normal tissues and those demonstrating all
      grades of CIN.

PMID- 9762943
TI  - Postchemotherapy residual masses in germ cell tumor patients: content, clinical
      features, and prognosis. Medical Research Council Testicular Tumour Working
      Party.
AB  - BACKGROUND: In a retrospective study that included a detailed histopathologic
      review, the clinicopathologic features of patients with germ cell tumors (GCT)
      and resectable residual masses after chemotherapy were assessed. METHODS:
      Histologic material from 153 patients was available for review. Recorded details
      included primary histologic diagnosis, location, size and number of metastases,
      marker levels before and after chemotherapy, and completeness of surgical
      excision. A median of seven histologic sections per resection were reviewed by
      two pathologists independently (and together when disagreement occurred). In each
      case, details were recorded regarding fibrosis, necrosis, hemorrhage, embryonal
      carcinoma (undifferentiated teratoma), yolk sac tumor, choriocarcinoma
      (trophoblastic tumor), differentiated teratoma (mature and immature), dysplasia
      in somatic tissues, and non- germ cell tumor (GCT) malignancies. The percentage
      of the sample that each of these components comprised was also estimated.
      RESULTS: The median postchemotherapy follow-up time was 7 years, and 38 of 153
      patients (25%) experienced disease progression. In a multivariate analysis,
      incomplete resection of all residual masses (in 38 patients) and the presence of
      malignant elements (in 23 patients) were independent risk factors for
      progression. In the subset of patients in whom all masses were completely
      resected, the presence of embryonal carcinoma (undifferentiated teratoma) was the
      single most significant risk factor for progression. Seven percent of patients
      had this factor, which was associated with a 2-year progression free survival
      rate of 12.5%, compared with 88.0% where this component was absent. CONCLUSIONS:
      Progression free survival can be predicted well by the completeness of excision
      of residual masses and the presence of malignant germ cell elements. The latter
      confers a relatively poor prognosis even if all of these elements are completely
      resected.

PMID- 9762944
TI  - Ovarian transposition by laparoscopy before radiotherapy in the treatment of
      Hodgkin's disease.
AB  - BACKGROUND: The use of inverted Y irradiation in the treatment of Hodgkin's
      disease with pelvic lymph node involvement can cause iatrogenic early menopause
      in young women as a result of ovarian exposure to radiation. Ovarian
      transposition protects the ovaries by removing them from the irradiation field.
      This surgical procedure, initially performed by laparotomy, can now be done by
      laparoscopy. METHODS: During the period July 1994 to April 1996, laparoscopic
      ovarian transposition was performed on 4 young women with Hodgkin's disease 1
      week before inverted Y radiotherapy. The surgical procedure, complications,
      length of hospitalization, and hormonal, clinical, and biologic results were
      evaluated. RESULTS: The mean duration of hospitalization was 4 days, and there
      were no postoperative complications. Iatrogenic menopause did not occur in any of
      the patients during the mean follow-up period of 20.75 months (range, 6-35
      months; median, 20 months). CONCLUSIONS: Laparoscopy offers many advantages over
      laparotomy for ovarian transposition. This procedure, which can be performed
      without opening the abdominal wall, is highly efficient, requires only a short
      period of hospitalization, and leads to few postoperative complications.
      Laparoscopy is an attractive alternative to laparotomy for ovarian transposition
      in young women with advanced Hodgkin's disease who require pelvic radiotherapy.

PMID- 9762945
TI  - Progress in improving diet to reduce cancer risk.
AB  - BACKGROUND: In an effort to decrease cancer risk among the population, national
      health objectives for the year 2000 included recommendations to decrease intake
      of dietary fat and alcohol and increase intake of fruits, vegetables, and grains.
      The purpose of this article is to assess trends in the intake of these dietary
      components relative to the national health objectives. METHODS: National food
      supply data and food consumption survey data were reviewed for their
      appropriateness for monitoring intake trends. Recent data from both sources are
      described and interpreted. RESULTS: Americans have made modest but important
      improvements in their diets in recent years and may meet the "Healthy People
      2000" dietary objectives aimed at decreasing cancer risk. Intake of fruits,
      vegetables, and grains are higher, and those of fat and alcohol are lower than
      they were at the beginning of the decade. These trends are consistent with recent
      improvements in mortality rates for those cancer sites with the strongest
      associations with diet: the colon/rectum, prostate, and breast. CONCLUSIONS:
      Although the average intake of fruits, vegetables, and grain products is higher,
      it should be noted that the objective represents the minimum recommendations.
      Within each of these major food groups, further improvements can be made. In
      addition, special efforts should be made to guide children toward improvements in
      their diets and to monitor the diets of children and other subgroups.

PMID- 9762946
TI  - Oral glutamine reduces the duration and severity of stomatitis after cytotoxic
      cancer chemotherapy.
AB  - BACKGROUND: Mouth sores and/or difficulty swallowing are common and painful
      consequences of cytotoxic chemotherapy for cancer. In previous studies oral
      glutamine was found to protect animals from the effects of whole abdominal
      radiation and methotrexate-induced enteritis. Glutamine also was found to reduce
      oral mucositis in a nonrandomized pilot study in humans. Therefore, the authors
      attempted to determine the efficacy of oral glutamine in a randomized, double
      blind, crossover trial in cancer patients receiving chemotherapy. METHODS: Twenty
      four patients (16 children and 8 adults) received glutamine or placebo (glycine)
      suspension (2 g amino acid/M2/dose twice daily) to swish and swallow on days of
      chemotherapy administration and for at least 14 additional days. Patients
      completed a calendar indicating days of mouth pain associated with each
      chemotherapy course and the effect of mouth pain on oral intake. RESULTS: Paired
      data indicated significant amelioration of stomatitis associated with glutamine
      administration after chemotherapy. The duration of mouth pain was 4.5 days less
      in chemotherapy courses in which glutamine supplementation was compared with
      placebo (Wilcoxon's signed rank test, P=0.0005). The severity of oral pain also
      was reduced significantly when glutamine was provided with chemotherapy (the
      amount of days mucositis restricted oral intake to soft foods [> or =Grade 2;
      Modified Eastern Cooperative Oncology Group grading system] was 4 days less with
      glutamine compared with placebo; Wilcoxon's signed rank test, P=0.002).
      CONCLUSIONS: Low dose oral glutamine supplementation during and after
      chemotherapy significantly reduced both the duration and severity of chemotherapy
      associated stomatitis. Oral glutamine appears to be a simple and useful measure
      to increase the comfort of many patients at high risk of developing mouth sores
      as a consequence of intensive cancer chemotherapy.

PMID- 9762947
TI  - Epidemiology of osteosarcoma and Ewing's sarcoma in childhood: a study of 305
      cases by the Children's Cancer Group.
AB  - BACKGROUND: The Children's Cancer Group conducted a case-control study to
      determine the role of a broad range of environmental and familial factors in the
      etiology of Ewing's sarcoma and osteosarcoma in children. These factors included
      radiation exposure and, for children with osteosarcoma, parental exposure to
      beryllium. METHODS: The parents of 152 children with osteosarcoma and 153
      children with Ewing's sarcoma were interviewed by telephone. Controls were
      obtained by random digit dialing and were matched to cases by age and race.
      RESULTS: Female osteosarcoma patients had earlier onset of breast development
      (age 11.4 vs. 11.8 years, P=0.03) and menarche (age 12.1 vs. 12.5 years, P=0.002)
      but no significant differences in growth, whereas male osteosarcoma patients were
      similar in age at the onset of secondary sexual characteristics but reported
      significantly less weight gain during their growth spurt (6.6 vs. 11.7 kg,
      P=0.003). For children with Ewing's sarcoma, the growth spurt began earlier (age
      12.1 vs. 12.7 years, P=0.12) and resulted in less weight and height gain (5.2 vs.
      9.7 kg, P=0.002, and 10.2 vs. 12.7 cm, P=0.02, respectively) for males, but no
      differences were observed among females. For factors not related to growth and
      development (including a wide range of occupational, medical, and household
      exposures), there was little evidence of an etiologic role with respect to either
      tumor type. CONCLUSIONS: Differences between cases and controls with respect to
      growth and development showed no consistent pattern. This study did not identify
      any important risk factors for either type of childhood bone tumor.

PMID- 9762948
TI  - A Phase I study of granulocyte-macrophage-colony stimulating factor/interleukin-3
      fusion protein (PIXY321) following ifosfamide, carboplatin, and etoposide therapy
      for children with recurrent or refractory solid tumors: a report of the
      Children's Cancer Group.
AB  - BACKGROUND: This Phase I trial was developed to determine the safety, biologic
      activity, and effects on hematopoietic recovery of PIXY321 following ifosfamide,
      carboplatin, and etoposide chemotherapy for children with recurrent or refractory
      solid tumors. METHODS: Children (age < 22 years at diagnosis) received ifosfamide
      1800 mg/m2/day x 5 days, carboplatin 400 mg/m2/day x 2 days, and etoposide 100
      mg/m2/day x 5 days, followed by daily subcutaneous administration of PIXY321.
      Dose-limiting toxicity was defined as Grade IV toxicity related to PIXY321.
      Pharmacokinetic and endogenous cytokine production studies were conducted during
      Course 1, and peripheral blood (PB) progenitor cell and receptor expression
      studies were conducted during Course 1 when the white blood cell count recovered
      to > or=1000/mm3. RESULTS: Twenty-four children received ifosfamide, carboplatin,
      and etoposide chemotherapy plus PIXY321, the latter at doses of 500 /g/m2/day
      (n=3), 750 microg/m2/day (n=6), 1000 microg/m2/day (n=9), or 500 microg/m2/twice
      a day (n=6). PIXY321 was well tolerated, with only 1 dose-limiting toxicity
      (chills, occurring at a dose of 750 microg/m2/day). The maximum tolerated dose
      was not reached in this study. The median days to absolute neutrophil count
      recovery (> or =1000/mm3) and platelet recovery (>100,000/mm3) during Course 1
      following PIXY321 (1000 microg/ m2/day) were 22 days (range, 5-33 days) and 20
      days (range, 5-31 days), respectively. There was a 2500, 5000, 3000, and 390%
      increase in PB granulocyte-macrophage colony-forming units, erythrocyte blast
      forming units, granulocyte erythrocyte macrophage and megakaryocyte colony
      forming units, and CD34+ cells, respectively. CONCLUSIONS: In summary, this
      pediatric Phase I trial demonstrated that PIXY321 was well tolerated by children
      and resulted in platelet recovery a median of 20 days after ICE chemotherapy and
      an increase in the number of PB progenitor cells above baseline. However, based
      on recent negative results with PIXY321 in randomized Phase II/III trials
      involving adult subjects, PIXY321 is not currently available for future trials
      involving children.

PMID- 9762949
TI  - Prenatal exposure to metronidazole and risk of childhood cancer: a retrospective
      cohort study of children younger than 5 years.
AB  - BACKGROUND: To evaluate the role of in utero exposure to metronidazole (a
      carcinogen in some animal models) and the risk of subsequent cancer, the authors
      conducted a retrospective cohort study of childhood cancer. METHODS: The cohort
      included 328,846 children younger than 5 years born to women enrolled in
      Tennessee Medicaid at any time between the last menstrual period (LMP) and the
      date of delivery. The cohort was identified by linking files of Tennessee
      Medicaid mothers ages 15-44 years and children and the children's birth and death
      certificates for the period January 1, 1975 through December 31, 1992. Exposure
      data were obtained from Medicaid pharmacy records and exposure was defined as
      filling a metronidazole prescription that had at least a day's supply between the
      30 days prior to the LMP and the date of delivery. Study cases were cohort
      children diagnosed with a first primary cancer before age 5 years, identified by
      linking the cohort with a statewide childhood cancer database for the study
      period. RESULTS: Cohort members contributed 1,172,696 person-years of follow-up
      for analysis, with children exposed (8.1%) and not exposed (91.9%) in utero to
      metronidazole contributing 79,716 and 1,092,980 person-years, respectively. Of
      952 children younger than 5 years in the statewide cancer database, 175 met study
      eligibility criteria. Of these, 42 had leukemia, 30 had central nervous system
      (CNS) tumors, 28 had neuroblastoma, and 75 had other cancers. Using Poisson
      regression modeling, children exposed to metronidazole in utero had no
      significant increase in adjusted relative risk (RR) for all cancers (RR: 0.81;
      95% confidence interval [95% CI], 0.41-1.59), leukemia (no exposed case), CNS
      tumors (RR: 1.23; 95% CI, 0.29-5.21), neuroblastomas (RR: 2.60; 95% CI, 0.89
      7.59), and other cancers (RR: 0.57; 95% CI, 0.18-1.82). CONCLUSIONS: The authors
      conclude that although there was no increase in risk for all cancers associated
      with in utero exposure to metronidazole, the observed increased risk for
      neuroblastomas, although not significant, requires further evaluation.

PMID- 9762950
TI  - Detection of chromogranin A mRNA in small cell lung carcinoma using a new, highly
      sensitive in situ hybridization method with a non-radioisotope oligonucleotide
      probe.

PMID- 9762951
TI  - The amnestic prodrome of Alzheimer's disease.

PMID- 9762952
TI  - The perception of phantom limbs. The D. O. Hebb lecture.
AB  - Almost everyone who has a limb amputated will experience a phantom limb--the
      vivid impression that the limb is not only still present, but in some cases,
      painful. There is now a wealth of empirical evidence demonstrating changes in
      cortical topography in primates following deafferentation or amputation, and this
      review will attempt to relate these in a systematic way to the clinical
      phenomenology of phantom limbs. With the advent of non-invasive imaging
      techniques such as MEG (magnetoencephalogram) and functional MRI, topographical
      reorganization can also be demonstrated in humans, so that it is now possible to
      track perceptual changes and changes in cortical topography in individual
      patients. We suggest, therefore, that these patients provide a valuable
      opportunity not only for exploring neural plasticity in the adult human brain but
      also for understanding the relationship between the activity of sensory neurons
      and conscious experience. We conclude with a theory of phantom limbs, some
      striking demonstrations of phantoms induced in normal subjects, and some remarks
      about the relevance of these phenomena to the question of how the brain
      constructs a 'body image.'

PMID- 9762953
TI  - Presymptomatic cognitive deficits in individuals at risk of familial Alzheimer's
      disease. A longitudinal prospective study.
AB  - A longitudinal study of asymptomatic individuals at risk of autosomal dominant
      familial Alzheimer's disease was performed to assess the earliest clinical and
      neuropsychological features of the disease. Over a 6-year period, 63 subjects
      underwent serial assessments. During the study, 10 subjects developed symptoms of
      episodic memory loss and subsequently progressed to fulfil criteria for possible
      or probable Alzheimer's disease. The mean time (+/-SD) from first assessment to
      the appearance of symptoms was 2.6+/-1.4 years. The subjects who remained well
      were similar to those who became clinically affected in terms of age, family
      history and initial Mini-Mental State Examination. Individuals who later became
      clinically affected already had significantly lower verbal memory (P=0.003) and
      performance IQ (P=0.030) scores at their first assessment, when they were
      ostensibly unaffected. Subsequent assessments showed progressive decline in
      multiple cognitive domains. Blinded assessment of serial imaging revealed the
      appearance of diffuse cerebral and medial temporal lobe atrophy in subjects only
      once they were clinically affected. These findings imply that in familial
      Alzheimer's disease cognitive decline predates symptoms by several years and that
      verbal memory deficits precede more widespread deterioration. This may have
      implications for the detection and treatment of Alzheimer's disease at an early
      stage.

PMID- 9762954
TI  - Competition between past and present. Assessment and interpretation of verbal
      perseverations.
AB  - Perseveration consists of the inappropriate repetition of a preceding behaviour
      when a new adapted response is expected. We have developed statistical tools that
      make it possible to reveal such perseverations, assess their significance and
      study their finer characteristics, such as their temporal course and impaired
      processing level. This approach is illustrated and evaluated through analyses of
      naming errors produced by three patients with impairments affecting different
      stages of the processing chain leading from visual perception to speech
      production. These examples of perseverations include the intrusion not only of
      whole words (patient R.A.V.) but also of isolated phonemes (patient D.U.M.) or of
      visual features (patient Y.M.) from previous trials. In all cases, the
      probability that an error is a perseveration from a previous trial is an
      exponentially decreasing function of the lag between the two trials considered.
      This suggests that perseverations reflect a decaying internal variable, such as
      an internal level of activation of previous utterances. Based on these empirical
      results, we put forward a tentative mechanism for the generation of
      perseverations: whenever a given processing level is deprived of its normal
      input, persistent activity inherited from previous trials is no longer overcome
      by current input, and is revealed in the form of perseverations.

PMID- 9762955
TI  - Quantitative MRI in patients with idiopathic generalized epilepsy. Evidence of
      widespread cerebral structural changes.
AB  - In patients with idiopathic generalized epilepsy (IGE), visual inspection of
      routine MRI is normal. However, pathological studies have shown microdysgenesis
      in grey and white matter in a large percentage of autopsies from cases of IGE.
      Recently, widespread structural changes not evident on visual inspection of high
      resolution MRI have been shown using quantitative MRI in patients with apparently
      focal cerebral dysgenesis. We sought to determine whether similar quantitative
      changes might be present in patients with IGE, reflecting possible underlying
      structural abnormalities. Twenty patients with juvenile myoclonic epilepsy, 10
      patients each with childhood absence epilepsy and juvenile absence epilepsy, five
      patients with tonic-clonic seizures on awakening and 30 control subjects had T1
      weighted volume acquisition MRI scans on a 1.5T GE scanner. The cerebral
      hemispheres were segmented semi-automatically, allowing the comparison of
      normalized cortical and subcortical matter volumes between groups, and
      investigation of the regional distribution of cortical and subcortical matter in
      individual subjects. Patients with IGE had significantly larger cortical grey
      matter volumes than control subjects. Significant abnormalities of the regional
      distribution of cerebral grey and subcortical matter were found in eight out of
      20 patients with juvenile myoclonic epilepsy, one out of 10 patients with
      childhood absence epilepsy, four out of 10 patients with juvenile absence
      epilepsy and two out of five patients with tonic-clonic seizures on awakening,
      but in none of the 30 control subjects. Using MRI-segmentation, we identified
      widespread cerebral structural changes in patients with various IGE syndromes.
      Quantitative MRI supports the existence of structural abnormalities in patients
      with IGE.

PMID- 9762956
TI  - Three cortical stages of colour processing in the human brain.
AB  - We used the technique of functional magnetic resonance imaging to chart the
      colour pathways in the human brain beyond V4. We asked subjects to view objects
      that were dressed in natural and unnatural colours as well as their achromatic
      counterparts and compared the activity produced in the brain by each condition.
      The results showed that both naturally and unnaturally coloured objects activate
      a pathway extending from V1 to V4, though not overlapping totally the activity
      produced by viewing abstract coloured Mondrian scenes. Normally coloured objects
      activated, in addition, more anterior parts of the fusiform gyrus, the
      hippocampus and the ventrolateral frontal cortex. Abnormally coloured objects, by
      contrast, activated the dorsolateral frontal cortex. A study of the cortical
      covariation produced by these activations revealed that activity in large parts
      of the occipital lobe covaried with each. These results, considered against the
      background of previous physiological and clinical studies, allow us to discern
      three broad cortical stages of colour processing in the human brain. The first is
      based on V1 and possibly V2 and is concerned mainly with registering the presence
      and intensity of different wavelengths, and with wavelength differencing. The
      second stage is based on V4 and is concerned with automatic colour constancy
      operations, without regard to memory, judgement and learning. The third stage,
      based on the inferior temporal and frontal cortex, is more concerned with object
      colours. The results we report, as well as the schema that we suggest, also allow
      us to reconcile the computational theory of Land, implemented without regard to
      cognitive factors such as memory and learning, and the cognitive systems of
      Helmholtz and Hering, which view such factors as critical in the determination of
      colours.

PMID- 9762957
TI  - Autosomal dominant cerebellar ataxia type I. MRI-based volumetry of posterior
      fossa structures and basal ganglia in spinocerebellar ataxia types 1, 2 and 3.
AB  - Twenty-six patients suffering from autosomal dominant cerebellar ataxia type I
      were subjected to a genotype-phenotype correlation analysis using molecular
      genetic assignment to the genetic loci for spinocerebellar ataxia type 1, 2 or 3
      (SCA1, SCA2, SCA3) and MRI-based volumetry of posterior fossa structures and
      basal ganglia nuclei. There was significant atrophy of the cerebellum and
      brainstem in all three SCA mutations compared with a group of 31 age- and sex
      matched controls. Comparison between the SCA groups showed that cerebellar and
      brainstem atrophy was more severe in SCA2 than in SCA1 and SCA3. Putaminal and
      caudate volume was reduced only in SCA3, but not in SCA1 and SCA2. A set of three
      morphological criteria was defined that enabled us to assign all SCA2 and SCA3
      patients correctly to the underlying genotype. In contrast, these criteria did
      not distinguish SCA1 from SCA2 and SCA3. Regression analysis failed to reveal a
      significant association between CAG repeat length and the volumes of the
      respective brain structures in any of the SCA mutant types. The present data
      provide in vivo evidence that SCA2 and SCA3 lead to distinct patterns of brain
      atrophy, while the atrophy changes in SCA1 overlap with both SCA2 and SCA3.

PMID- 9762958
TI  - The role of the human motor cortex in the control of complex and simple finger
      movement sequences.
AB  - We evaluated the effects of high-frequency repetitive transcranial magnetic
      stimulation (rTMS) over the primary motor cortex (M1) at different stimulus
      intensities on finger sequences of varying complexity. Eighteen subjects played
      unimanual finger sequences of different complexity on an electronic piano. For
      each finger sequence, 16 notes were played to the 2 Hz beat of a metronome. After
      the first four notes, rTMS was applied to the scalp location overlying the hand
      motor representation for approximately 2 s. Accuracy and timing errors were
      analysed. Stimulation over the M1 had a differential effect on sequences of
      different complexity. Stimulus intensities capable of disrupting the performance
      of a complex sequence did not affect simple sequences. To disrupt simple
      sequences, the stimulus strength had to be augmented. This effect was
      characteristic of the contralateral M1 position (five other scalp locations were
      also stimulated). It is argued that the differential effect of rTMS on simple and
      complex sequences is probably due to interference with M1 function. Interference
      with the lateral premotor cortex (PMC) may play an additional role. The
      particular relevance of the M1 is supported by results in a patient with PMC
      stroke. The present findings suggest that the human M1 plays a greater role in
      the performance of complex than of simple finger movement sequences. One possible
      explanation could be that the human M1 is not only an executive motor area but
      can also contribute to movement sequence organization.

PMID- 9762959
TI  - Regional sympathetic function in high spinal cord injury during mental stress and
      autonomic dysreflexia.
AB  - Centrally mediated sympathetic stimulation of subjects who have suffered a spinal
      cord injury (SCI) does not activate the decentralized part of the body below the
      level of the lesion, whereas experimental data indicate an exaggerated response
      above the level of the lesion. SCI subjects may exhibit an autonomic dysreflexia
      reaction following afferent stimulation below the level of the lesion. In order
      to investigate the function of the sympathetic nervous system above and below the
      level of the lesion, regional noradrenaline spillover was measured by means of
      steady-state isotope dilution technique above (forearm) and below (leg) the level
      of the lesion at baseline, during mental stress and following bladder stimulation
      in nine SCI subjects (mean age 41 years; level of injury C7-T4; mean duration of
      injury 13.8 years). The results from the SCI subjects were also compared with
      those from 10 weight- and age-matched control subjects, both at rest and during
      mental stress. Body composition was determined by dual energy X-ray
      absorptiometry scanning and arm/leg blood flow by occlusion plethysmography. At
      baseline, total and regional noradrenaline spillover did not differ between the
      groups. Mental stress increased mean arterial pressure in both groups. Heart rate
      (76 versus 64 beats/min; P < 0.05) and arm noradrenaline spillover (2.73 versus
      1.71 pmol/min/100 g; P < 0.05) increased more in spinal cord injury subjects than
      in control subjects, whereas total body (2826 versus 3783 pmol/min; P < 0.01) and
      leg noradrenaline spillover (0.23 versus 0.41 pmol/min/100 g; P < 0.05) increased
      only in the control group. During bladder stimulation, SCI subjects reacted with
      a marked increase in mean arterial pressure and leg noradrenaline spillover (from
      0.06 to 0.91 pmol/min/100 g; P < 0.05) and their leg blood flow decreased.
      Regional and total noradrenaline clearance were similar in the two groups. In
      conclusion, peripheral afferent stimulation below the level of the lesion in
      spinal cord injury subjects gives rise to a marked noradrenaline spillover from
      the decentralized part of the sympathetic nervous system suggesting a remaining,
      but qualitatively altered, neuronal function. Centrally mediated stimulation
      induced an exaggerated response above the level of the lesion.

PMID- 9762960
TI  - Writing disorders in Italian aphasic patients. A multiple single-case study of
      dysgraphia in a language with shallow orthography.
AB  - We report results of a writing task given to 53 mildly to moderately aphasic
      Italian subjects. The task was designed to test the writing performance along the
      subword-level routine for the spelling of regular words and non-words, and along
      the lexical routine for the spelling of irregular words. The aim of the study was
      to identify the incidence of different dysgraphic subtypes in Italian, a language
      that is considered to have shallow orthography. Its spelling, however, is not
      completely free of ambiguity. A five-part writing task was used: (i) words with
      regular one-sound-to-one-grapheme conversion; (ii) words with regular syllabic
      conversion; (iii) words with ambiguous transcription; (iv) loan-words; and (v)
      non-words. For regular words, the effects of word length and word frequency, and
      of the variables determining the complexity of the acoustic-to-phonological
      conversion (continuant versus plosive phones; consonant-vowel sequence versus
      doubled consonants or consonant clusters) were also considered. Patients'
      performances were classified according to the presence of a dissociation between
      (i) regular words and non-words, (ii) regular words and words with unpredictable
      spellings, and (iii) one-to-one and syllabic conversions. The 53 aphasic patients
      span the whole spectrum of dysgraphic taxonomy. Thirty-nine patients, in
      particular, manifested a dissociated pattern of performance. Eighteen patients
      showed a prevalent surface dysgraphic pattern and seven a phonological one, while
      11 patients showed a mixed pattern (i.e. a better performance for regular words
      than for ambiguous words or regular non-words). Three patients showed a specific
      deficit for regular syllabic conversion rules only. A high rate of 'mixed
      dysgraphia' suggests either a mutual interaction of the two impaired routines
      when regular words are written, or two separate functional lesions: one at the
      level of the auditory-to-phonological conversion procedure, the other at the
      level of the orthographic output lexicon.

PMID- 9762962
TI  - Reciprocal inhibitory visual-vestibular interaction. Visual motion stimulation
      deactivates the parieto-insular vestibular cortex.
AB  - The vestibular system--a sensor of head accelerations--cannot detect self-motion
      at constant velocity and thus requires supplementary visual information. The
      perception of self-motion during constant velocity movement is completely
      dependent on visually induced vection. This can be linear vection or circular
      vection (CV). CV is induced by large-field visual motion stimulation during which
      the stationary subject perceives the moving surroundings as being stable and
      himself as being moved. To determine the unknown cortical visual-vestibular
      interaction during CV, we conducted a PET activation study on CV in 10 human
      volunteers. The PET images of cortical areas activated during visual motion
      stimulation without CV were compared with those with CV. Hitherto, CV was
      explained neurophysiologically by visual-vestibular convergence with activation
      of the vestibular nuclei, thalamic subnuclei and vestibular cortex. If CV were
      mediated by the vestibular cortex, one would expect that an adequate visual
      motion stimulus would activate both the visual and vestibular cortex. Contrary to
      this expectation, it was shown for the first time that visual motion stimulation
      with CV not only activates a medial parieto-occipital visual area bilaterally,
      separate from middle temporal/medial superior temporal areas, it also
      simultaneously deactivates the parieto-insular vestibular cortex. There was a
      positive correlation between the perceived intensity of CV and relative changes
      in regional CBF in parietal and occipital areas. These findings support a new
      functional interpretation: reciprocal inhibitory visual-vestibular interaction as
      a multisensory mechanism for self-motion perception. Inhibitory visual-vestibular
      interaction might protect visual perception of self-motion from potential
      vestibular mismatches caused by involuntary head accelerations during locomotion,
      and this would allow the dominant sensorial weight during self-motion perception
      to shift from one sensory modality to the other.

PMID- 9762961
TI  - Limb-girdle muscular dystrophy in Guipuzcoa (Basque Country, Spain).
AB  - The concept of limb-girdle muscular dystrophy (LGMD) is changing rapidly due to
      the advances in molecular genetics. Recently, seven different gene loci have been
      described, demonstrating that limb-girdle muscular dystrophy is a heterogeneous
      syndrome, which includes different diseases with a similar phenotype. In isolated
      populations which have little genetic exchange with neighbouring populations, an
      accumulation of cases may be found. We carried out an epidemiological study in
      Guipuzcoa, a small mountainous Basque province in northern Spain, and found the
      highest prevalence rate of LGMD described so far: 69 per million. Genetic studies
      demonstrated that 38 cases corresponded to the LGMD2A type, due to calpain-3 gene
      mutations. Only one patient with alpha-sarcoglycanopathy was found, and in 12
      patients the genetic defect was not identified. Moreover, the particular calpain
      3 mutation predominant in Basque chromosomes (exon 22, 2362AG-->TCATCT), has only
      been rarely found in the rest of the world. This observation strongly suggests a
      founder effect in the indigenous population of Guipuzcoa. The clinical
      characteristics of the patients with calpain-3 gene mutations were quite
      homogeneous and different from the other groups (sarcoglycanopathy and unknown
      gene defect), allowing for a precise clinical diagnostic. The disease onset was
      between the ages of 8 and 15 years, in most cases in the pelvic girdle, and the
      patients became wheelchair-bound between 11 and 28 years after onset. No
      pseudohypertrophy of calves or contractures were observed. No clear correlations
      were found between the nature and site of the mutation and the resulting
      phenotype.

PMID- 9762963
TI  - The spatial distribution of visual attention in hemineglect and extinction
      patients.
AB  - We studied the visual field distribution of speed and accuracy of manual
      responses to small brief light flashes, in patients with left hemineglect or
      extinction resulting from right hemisphere vascular lesions and in brain-damaged
      and healthy control subjects. All patients with right hemisphere lesions showed a
      greater impairment in both the speed of response and the detection rate in the
      contralesional than in the ipsilesional hemifield. This interfield difference
      increased with the eccentricity of stimulus presentation and was especially
      pronounced in neglect patients who showed a paradoxical increase in speed of
      response and detection rate at increasingly larger eccentricities in the
      ipsilesional hemifield. We hypothesize that both the contralesional slowing down
      and the ipsilesional speeding up of the response depends upon an exaggerated
      gradient of attention towards the ipsilesional hemifield. To assess whether these
      abnormalities concern automatic or controlled attentional processes, in a second
      experiment, we manipulated the predictability of the side of the stimulus
      presentation by using blocked rather than randomized stimulus presentations. This
      resulted in a speeding up of responses in both hemifields thus showing that the
      patients were able to focus attention to the side of stimulus presentation
      voluntarily. However, there was no modification of the contra-ipsilesional
      differences which, therefore, are likely to be related to abnormal automatic
      processes rather than controlled attention.

PMID- 9762964
TI  - Precision grip and Parkinson's disease.
AB  - In order to investigate sensorimotor processing and force development in
      Parkinson's disease, 16 patients, four patients with hemiparkinsonism and 12 age
      matched normal subjects were assessed during lifting and holding of an object in
      a precision grip between thumb and forefinger, or holding the object in this grip
      at a fixed height above a table. In the former case, object loading could be
      changed between lifts without warning. In the latter case, unexpected step load
      changes to the object were applied to the object with a torque motor. All
      procedures could be applied with or without visual control of the hand and the
      object. Normal subjects lifted an unpredictable load employing the grip force
      parameters used in the preceding lift. If a load change was encountered, the
      parameters became adapted to the new conditions during the lift, modulating grip
      forces to match the loading. Parkinsonian patients retained this strategy and the
      ability to regulate grip forces according to load. Under all conditions, however,
      parkinsonian subjects developed abnormally high grip forces in both the lift and
      the hold phase, although the ratio of these forces remained normal. Lifting
      height was normal in parkinsonian subjects, but the duration of the lifting task
      was significantly prolonged, due to a marked slowing in the rate of grip force
      development in the lead-up to object lift-off and to prolongation of the movement
      phase. Forewarning of object loading, with or without visual control, did not
      reduce timing deficits or improve the rate of grip force development. However, it
      did allow parkinsonian subjects to reduce the safety margin significantly.
      Responses to step load changes imposed during holding without visual control
      showed minor abnormalities in the parkinsonian patients: onset latencies and EMG
      activity in the first dorsal interosseus and thenar muscles were normal up to 140
      ms after displacement. Subsequent EMG activity in the first dorsal interosseus
      remained largely normal, but activity later in the slip response (140-210 ms),
      subject to voluntary influence, was reduced in the thenar muscle. Differences
      were less marked under visual conditions, but remained significant. We concluded
      that the internal parameter set for lifting an object in a precision grip and the
      automatic processes adapting precision grip to actual conditions are intact in
      Parkinson's disease. However, parkinsonian subjects generate abnormally high grip
      forces and require longer than normal subjects to complete a lift, particularly
      with lighter loads. This deterioration in performance reflects both reduced
      effectiveness of sensorimotor processing and impairment in the rate of force
      development in Parkinson's disease.

PMID- 9762965
TI  - Neurophysiological evidence of neuroplasticity at multiple levels of the
      somatosensory system in patients with carpal tunnel syndrome.
AB  - The human somatosensory cortex (S1) is capable of modification after partial
      peripheral deafferentation, but it is not known whether spinal and brainstem
      changes contribute to this process. We recorded spinal, brainstem and cortical
      somatosensory evoked potentials following ulnar nerve stimulation in patients
      affected by unilateral carpal tunnel syndrome with EMG evidence of chronic
      alterations in median nerve sensorimotor conduction at the wrist lasting at least
      4 weeks, and compared them with those from the unaffected hand and with those
      obtained in a control group. Amplitudes of spinal N13 and brainstem P14
      potentials following stimulation of the ulnar nerve ipsilateral to the
      deafferented median nerve were greater than those following stimulation of the
      contralateral ulnar nerve. Side-to-side amplitude differences in N13 and P14 were
      greater in patients than in the control group. Parietal N20 and P27 potentials,
      supposedly generated in S1, were also significantly increased. The present
      results suggest that a chronic pathological modification of peripheral
      sensorimotor inputs is associated with changes in neural activity at multiple
      sites of the somatosensory system. Changes in spinal and brainstem structures
      could contribute to the mechanisms subserving changes in the S1. Changes in
      synaptic strength and unmasking inputs secondary to disconnection of the normally
      dominant inputs to the 'median nerve' cortex may be the mechanisms underlying
      ulnar nerve SEP changes.

PMID- 9762966
TI  - Interhemispheric neural summation in the absence of the corpus callosum.
AB  - One subject with full forebrain commissurotomy (L.B.), two with callosotomy (J.W.
      and M.E.), one with callosal agenesis (R.B.) and 10 normal subjects performed a
      simple reaction time task in which visual stimuli were either presented singly in
      one or other visual field, or in both visual fields simultaneously. Reaction
      times were faster to double stimuli than to single ones, but in the normal
      subjects this 'redundancy gain' did not exceed that predicted by probability
      summation (the horse-race model). In the four subjects lacking the corpus
      callosum, the gain did exceed that predicted by probability summation when the
      stimuli were brighter than the background, implying subcortical neural summation.
      In the three surgical cases (L.B., J.W. and M.E.) the gain was greatly diminished
      when the stimuli were equiluminant with the background, suggesting that neural
      summation occurred at the collicular level. In normal subjects, callosal transfer
      may ensure that at least some degree of interhemispheric neural summation occurs,
      even with unilateral input. The acallosal subject (R.B.) was anomalous in that
      neural summation was not diminished by equiluminance.

PMID- 9762967
TI  - Just when you think you've seen it all: the imaging evolution.

PMID- 9762968
TI  - The situation of diagnostic radiology training programs and their graduates in
      1997.
AB  - OBJECTIVE: In light of concerns about the job market, the American College of
      Radiology studied the employment situation of 1997 graduates from diagnostic
      radiology training programs and the status and plans of these programs. MATERIALS
      AND METHODS: In an April-May 1997 survey and in a December 1997 follow-up, the
      American College of Radiology asked a 50% random sample of diagnostic radiology
      residency directors about their programs and about the employment situation of
      their 1997 residency and fellowship graduates. Of those surveyed, 89% responded.
      We compared these findings with those from a similar 1996 survey. The test of
      statistical significance was p < or = .05. RESULTS: All diagnostic residency and
      fellowship graduates who wanted to work were employed within 6 months after
      graduation. Approximately 95% of graduates had positions that directors believed
      to reasonably match their training and personal employment goals. Outcomes were
      similar across all fellowship fields except nuclear medicine, a field in which
      graduates had greater difficulty finding jobs. The completed plus planned changes
      in program size will lead to a 13-14% reduction in the annual number of
      graduates. As in previous years, by late April to mid May 1997, 93% of beginning
      year residency slots were filled. However, the percentage of beginning residents
      who are international medical graduates increased. In 1997, residency program
      directors were more optimistic about graduates' job prospects than in 1996, and
      there was a statistically significant increase from 1996 in the proportion of
      fellowship graduates, according to directors, who had found jobs that fit their
      goals and training. CONCLUSION: Unemployment continues to be low. The 1997 job
      market has improved over the 1996 job market, but job prospects in nuclear
      medicine continue to be more problematic than in other subspecialties.

PMID- 9762969
TI  - Constructing a curriculum vitae: the radiologist's resume.

PMID- 9762970
TI  - False-negative core biopsy of the breast.

PMID- 9762971
TI  - Preston Hickey lecture. We are radiologists.

PMID- 9762972
TI  - Current concepts in contrast media-induced nephropathy.

PMID- 9762973
TI  - Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade:
      comparison of macromolecular and small-molecular contrast media.
AB  - OBJECTIVE: The endothelial integrity of microvessels is disrupted in malignant
      tumors. Quantitative assays of tumor microvascular characteristics based on
      dynamic MR imaging were correlated with histopathologic grade in mammary soft
      tissue tumors. MATERIALS AND METHODS: A spectrum of tumors, benign through highly
      malignant, was induced in 33 female rats by administration of N-ethyl-N
      nitrosourea, a potent carcinogen. Dynamic contrast-enhanced MR imaging was
      performed using a small-molecular contrast medium (gadopentetate, molecular
      weight = 0.5 kDa) and a macromolecular contrast medium (albumin-(Gd-DTPA)30,
      molecular weight = 92 kDa) at an interval of 1-2 days. Permeability surface area
      product (PS), as estimated by the corresponding endothelial transfer coefficient
      (K(PS)), and fractional plasma volume (fPV) were calculated for each tumor and
      each contrast agent using a two-compartment bidirectional kinetic model. MR
      imaging microvascular characteristics were correlated with histopathologic tumor
      grade. RESULTS: Tumor permeability to macromolecular contrast medium,
      characterized by K(PS), showed a highly positive correlation with tumor grade (r2
      = .76, p < 10(-10)). K(PS) values were zero for all benign and some low-grade
      carcinomas, greater than zero in all other carcinomas, and increased in magnitude
      with higher tumor grade. A considerably smaller but significantly positive
      correlation was found between fPV and tumor grade using macromolecular contrast
      medium (r2 = .25, p < .003). No correlation between K(PS) or fPV values and tumor
      grade was found using gadopentetate (r2 = .01, p > .95 and r2 = .03, p > .15,
      respectively). CONCLUSION: Quantitative tumor microvascular permeability assays
      generated with macromolecular MR imaging contrast medium correlate closely with
      histologic tumor grade. No significant correlation is found using small-molecular
      gadopentetate.

PMID- 9762974
TI  - The role of helical CT in the assessment of cervical spine injuries.

PMID- 9762975
TI  - The cost-effectiveness of oblique radiography in the exclusion of C7-T1 injury in
      trauma patients.
AB  - OBJECTIVE: The purpose of our study was to compare the cost-effectiveness of
      bilateral oblique radiography with that of CT for excluding C7-T1 injury in
      trauma patients. MATERIALS AND METHODS: Using a historical cohort model, we
      retrospectively studied two distinct groups of trauma patients. In the first
      group, which included 196 patients, CT was performed to show C7-T1 anatomy when
      this region was not adequately revealed on initial three-view cervical spine
      radiography. In the second group, which included 129 patients, routine three-view
      radiography was complemented by bilateral oblique views. If these five views
      failed to adequately reveal C7-T1 anatomy, CT was then performed to show the
      cervicothoracic junction. Using Medicare reimbursement data, we then compared the
      cost-effectiveness of CT with that of oblique radiography in terms of cost per
      cervical spine imaged completely to the level of C7-T1. RESULTS: In the first
      group, 50 (26%) of 196 patients underwent CT when C7-T1 anatomy was not
      adequately revealed on routine three-view cervical spine radiography. In the
      second group, only 17 (13%) of the 129 patients required CT when five-view
      radiography failed to adequately reveal C7-T1 anatomy. This difference was
      statistically significant (p < .01). The cost per completely imaged cervical
      spine was $92.00 when bilateral oblique radiographs were routinely obtained,
      compared with $116.28 per completely imaged cervical spine when these views were
      not obtained. CONCLUSION: Because bilateral oblique radiography appears to be
      cost-effective for the exclusion of cervical spine injuries, we suggest that it
      be performed routinely.

PMID- 9762976
TI  - MR imaging of tears of discoid lateral menisci.
AB  - OBJECTIVE: The purpose of this study was to determine the positive predictive
      value (PPV) for diagnosis of discoid lateral meniscal tear using MR imaging and
      to describe various patterns of such tears in the knee. SUBJECTS AND METHODS: MR
      reports of 77 patients (10-67 years old) who underwent prospective MR imaging
      that led to a diagnosis of discoid lateral meniscal tear were correlated with
      arthroscopic results. MR images obtained in 71 patients confirmed to have discoid
      lateral meniscial tear were retrospectively reviewed for the presence, site, and
      pattern of discoid lateral meniscal tear, including type of displacement of the
      torn segment. MR abnormalities were correlated with arthroscopic findings.
      RESULTS: For the prospective MR interpretations, the PPV for discoid meniscus was
      92%. PPV for discoid meniscal tear was 57%. PPVs for individual types of discoid
      meniscal tears were 46% (peripheral tear, 19/41), 76% (peripheral tear with
      horizontal tears, 16/21), 56% (horizontal tear, 5/9), 50% (transverse tear, 1/2),
      67% (horizontal tear combined with transverse tear, 2/3), and 100% (longitudinal
      tear, 1/1). Peripheral tear alone and peripheral tear with horizontal tear were
      the most common types of tears (n = 20, 28%). Multiple tears (n = 34, 48%) were
      common. Displacement of the torn segments was seen in 51 patients (72%).
      CONCLUSION: MR imaging has a low PPV for diagnosing discoid lateral meniscal
      tear. Peripheral tear alone and peripheral tear with horizontal tear were the
      most common types of tears, and displacement of the torn segment was frequent.

PMID- 9762977
TI  - Normal and abnormal medial meniscocapsular structures: MR imaging and sonography
      in cadavers.
AB  - OBJECTIVE: The purpose of this study was to develop imaging criteria for the
      diagnosis of meniscocapsular separation by correlating findings on MR imaging, MR
      arthrography, and sonography of normal and abnormal medial meniscocapsular
      structures with corresponding anatomic sections in cadavers. MATERIALS AND
      METHODS: Eight cadaveric knee specimens were examined with MR imaging, MR
      arthrography, and sonography before arthroscopy. In six specimens the following
      lesions were arthroscopically created: meniscocapsular separation (n = 3), medial
      collateral ligament (MCL) tear (n = 3), tear of the meniscofemoral extension of
      the deep MCL (n = 2), and coronary ligament tear (n = 2). After arthroscopy, all
      imaging studies were repeated. The specimens were sectioned for correlation with
      imaging studies. RESULTS: MR findings that correlated with meniscocapsular
      separation were interposition of fluid between the meniscus and the MCL,
      irregular meniscal outline, and increased distance between the meniscus and the
      MCL. On MR arthrography meniscocapsular separation correlated with interposition
      of contrast medium between the meniscus and the MCL. Tears of the meniscofemoral
      extension of the deep MCL were best shown on MR arthrography. Sonography showed
      deep and superficial MCL lesions but did not show meniscocapsular separations.
      CONCLUSION: In arthroscopically created meniscocapsular separation, the lesion is
      suggested on MR images when fluid is interposed between the meniscus and the MCL,
      when the meniscal outline is irregular, or when the distance between the meniscus
      and the MCL is increased. On MR arthrograms, a meniscocapsular separation is
      suggested when contrast medium is interposed between the meniscus and the MCL.
      Sonography does not allow accurate diagnosis of meniscocapsular separation.

PMID- 9762978
TI  - Elastofibroma dorsi: prevalence in an elderly patient population as revealed by
      CT.
AB  - OBJECTIVE: We wanted to determine the prevalence and appearance of elastofibroma
      dorsi in an elderly patient population (n = 258) who underwent CT of the chest
      for reasons other than to evaluate posterolateral chest wall pain, stiffness, or
      a mass. CONCLUSION: Five elastofibromas were detected in four patients; none of
      these elastofibromas were noted at initial examination. Our study suggests that
      the prevalence of elastofibroma dorsi revealed by CT is 2%, which is lower than
      the 11-24% found in autopsy series but higher than expected for such a rare
      tumor. Elastofibroma dorsi typically has a layered appearance on CT; however, in
      our study, homogeneous soft-tissue attenuation was noted. The diagnosis is often
      missed prospectively. Familiarity with the location and imaging appearance of
      elastofibroma dorsi may enhance detection and characterization of posterolateral
      chest wall masses in elderly patients.

PMID- 9762979
TI  - Vascular leiomyoma of an extremity: MR imaging-pathology correlation.
AB  - OBJECTIVE: The objective of our study was to analyze MR images of vascular
      leiomyoma of the extremity and to compare these images with histopathologic
      findings to determine if a correlation exists. CONCLUSION: T2-weighted MR images
      of vascular leiomyoma of an extremity showed a mass with mixed areas that were
      both hyper- and isointense to skeletal muscle and also revealed a hypointense
      rim; these images correlate with histopathologic findings of smooth muscle,
      vessels, fibrous tissue, an intravascular thrombus, and a fibrous capsule.

PMID- 9762981
TI  - Osteonecrosis of the knee in an HIV-infected patient.

PMID- 9762980
TI  - Rapid diagnosis and treatment of a traumatic atlantooccipital dissociation.

PMID- 9762982
TI  - CT colonography with three-dimensional problem solving for detection of colonic
      polyps.
AB  - OBJECTIVE: We performed CT colonography in patients referred for conventional
      colonoscopy, interpreted the axial images, and used commercially available
      software to reconstruct endoluminal perspective views to differentiate polyps
      from folds. SUBJECTS AND METHODS: We prospectively examined 44 patients (27 men
      and 17 women; mean age, 58 years old) with CT colonography by interpreting the
      axial images and using three-dimensional rendering for problem solving only. The
      CT scans were interpreted by two radiologists who were unaware of patients'
      histories as revealed by colonoscopic findings. The findings on colonography were
      compared with those of conventional colonoscopy to determine sensitivity,
      specificity, time spent on interpretation, and confidence of interpretation.
      RESULTS: Colonoscopy showed normal findings in 28 patients and 22 polyps in the
      remaining 16 patients. Six polyps were 8 mm or larger, three were 5-7 mm, and 13
      were 5 mm or smaller. The findings of the two observers revealed an overall
      sensitivity of 50% and 38%, respectively, and a specificity of 93% and 86%,
      respectively. Sensitivity for polyps larger than 8 mm was 83% and specificity was
      100% for both observers. The average amount of time spent on interpretation was
      28 min 30 sec (range, 14-65 min). Both observers used the endoluminal view for
      differentiating folds from polyps in 23 (52%) of 44 patients, which had only
      minimal impact on interpretation time. CONCLUSION: CT colonography can be
      performed and the images interpreted using currently available hardware and
      software by initially using the axial images to search for polyps of significant
      size. Endoluminal views should be used only when necessary to help distinguish
      normal folds from fixed raised lesions that are suggestive of polyps.

PMID- 9762983
TI  - Using unenhanced helical CT with enteric contrast material for suspected
      appendicitis in patients treated at a community hospital.
AB  - OBJECTIVE: We evaluated the accuracy of unenhanced helical CT with enteric
      contrast material in the diagnosis of appendicitis in children and adults treated
      at a community hospital. SUBJECTS AND METHODS: Over an 8-month period, 100
      consecutive patients with right lower quadrant pain and suspected appendicitis
      were prospectively evaluated. Thin-collimation helical CT scanning was performed
      after administration of enteric contrast material. CT interpretations were
      correlated with surgical pathology (45 patients) and clinical follow-up (55
      patients). RESULTS: The findings of 33 CT scans were interpreted as positive for
      appendicitis (29 true-positives and four false-positives), and the findings of 67
      were interpreted as negative for appendicitis (66 true-negatives and one false
      negative). Sensitivity was 97%, specificity was 94%, accuracy was 95%, positive
      predictive value was 88%, and negative predictive value was 99%. In the 67 CT
      scans with negative findings for appendicitis, an alternative diagnosis was made
      for 36 patients (54%). CONCLUSION: Unenhanced helical CT with enteric contrast
      material for the evaluation of appendicitis can be implemented in a community
      hospital. In our study, such imaging achieved excellent accuracy.

PMID- 9762984
TI  - Small-bowel perforation by a foreign body.

PMID- 9762985
TI  - Performing radiologic gastrostomy or gastrojejunostomy in patients with malignant
      ascites.
AB  - OBJECTIVE: We describe our protocol for performing decompression radiologic
      gastrostomy and gastrojejunostomy in patients with ascites and small-bowel
      obstruction. We also assess the technical success rate, the complications, and
      the morbidity and mortality in 45 patients who underwent radiologic gastrostomy.
      MATERIALS AND METHODS: Forty-five consecutive patients with ascites associated
      with metastatic ovarian cancer underwent a radiologic gastrostomy or
      gastrojejunostomy with gastropexy. Six patients underwent gastrostomy, and 39
      patients underwent gastrojejunostomy. Locking catheters were placed using the
      Seldinger technique after gastropexy in all patients. Paracentesis was performed
      before gastrostomy or gastrojejunostomy. Additional serial paracenteses were
      performed after the procedure when reaccumulation of ascites close to the site of
      gastropexy was detected on follow-up sonography. RESULTS: Forty-five procedures
      were attempted. The technical success rate was 97.8%. The complication rate was
      15.6%. Three major complications (6.7%) and four minor complications (8.9%)
      occurred. One procedure-related death (2.2%) occurred 16 days after
      gastrojejunostomy. CONCLUSION: Radiologic gastrostomy and gastrojejunostomy can
      be performed safely in patients with ascites if the patients undergo paracentesis
      first and if the reaccumulation of ascites is prevented after tube placement. In
      patients with ascites, gastropexy plays an important role in preventing
      pericatheter leakage. Ascites and peritoneal carcinomatosis should not be
      considered contraindications for radiologic gastrostomy or gastrojejunostomy.

PMID- 9762986
TI  - Abdominal manifestations of posttransplantation lymphoproliferative disorder.
AB  - The abdominal manifestations of posttransplantation lymphoproliferative disorder
      show wide variability with potential involvement of all organ systems. The
      radiologist should be aware of this entity when evaluating patients who have
      undergone transplantation; both clinical and radiologic findings can mimic other
      disease processes. Suggestive lesions should prompt a search for additional areas
      of involvement. In our experience, although sonography can reveal
      posttransplantation lymphoproliferative disorder of the abdominal viscera, CT
      more adequately depicts the full extent of disease involvement. Distinguishing
      between monomorphic and polymorphic subtypes, though important for treatment
      planning, is not possible by imaging characteristics alone. Therefore, tissue
      diagnosis is warranted.

PMID- 9762987
TI  - Gas lock obstruction of the colon: Ogilvie's syndrome revisited.

PMID- 9762988
TI  - Peritoneal encapsulation: CT appearance.

PMID- 9762989
TI  - Hepatic cavernous hemangioma: sonographic patterns and speed of contrast
      enhancement on multiphase dynamic MR imaging.
AB  - OBJECTIVE: Our purpose was to investigate a correlation between the speed of
      contrast enhancement in patients with hepatic cavernous hemangioma revealed by
      dynamic MR imaging and the internal echo pattern revealed by sonography.
      MATERIALS AND METHODS: Forty-five patients underwent multiphase IV contrast
      enhanced dynamic MR imaging that revealed 71 hepatic cavernous hemangiomas less
      than 4 cm in diameter; the MR findings were compared with the sonographic
      findings in these patients. On MR imaging, the hemangiomas were classified as
      rapid-, intermediate-, and slow-enhancing. We classified sonographic features as
      hypoechoic, iso- or mixed-echoic, and hyperechoic according to the relative
      echogenicity seen between lesions and the surrounding hepatic parenchyma.
      Sonographic patterns and MR imaging findings of individual lesions were then
      compared. RESULTS: Rapid-enhancing hemangiomas revealed on dynamic MR imaging
      tended to be hypoechoic on sonography (18/24, 75%; p = .0143), and lesions that
      were slow-enhancing on MR imaging tended to be hyperechoic (26/29, 90%; p <
      .0001). Hypoechoic lesions on sonography tended to be rapid-enhancing on dynamic
      MR imaging (18/18, 100%). Likewise, hyperechoic lesions on sonography tended to
      be slow-enhancing on MR imaging (26/33, 79%; p = .0009). CONCLUSION: In most
      patients with hepatic cavernous hemangiomas, we found that the speed of contrast
      enhancement on multiphase dynamic MR imaging enabled us to predict the echo
      pattern in sonography and vice versa.

PMID- 9762990
TI  - MR cholangiography in primary sclerosing cholangitis.
AB  - OBJECTIVE: The purpose of this study was to evaluate the ability of MR
      cholangiography to reveal the characteristics of biliary abnormalities found in
      primary sclerosing cholangitis. CONCLUSION: Our results suggest that MR
      cholangiography could be useful in the diagnosis of primary sclerosing
      cholangitis. Slightly dilated peripheral bile ducts unconnected to the central
      ducts in several hepatic segments are a characteristic MR sign of primary
      sclerosing cholangitis. However, other studies are necessary to establish the
      usefulness of MR cholangiography in relation to other imaging techniques for
      evaluating primary sclerosing cholangitis.

PMID- 9762992
TI  - Immediate increase in arterial blood flow in embolized hepatic segments after
      portal vein embolization: CT demonstration.
AB  - OBJECTIVE: This study was conducted to determine whether an immediate change
      occurs in the blood flow distribution in hepatic segments after segmental portal
      vein embolization. CONCLUSION: We found an immediate change in the distribution
      of blood flow in the liver after embolization; with portal vein embolization, we
      found an immediate increase in the hepatic artery blood flow in the affected
      segments.

PMID- 9762991
TI  - Percutaneous hepatic infarction therapy for hepatocellular carcinoma.
AB  - OBJECTIVE: We percutaneously injected ethanol into small vessels afferent to
      tumor nodules to induce hepatic infarction in areas of tumor caused by
      hepatocellular carcinoma. CONCLUSION: Percutaneous hepatic infarction therapy
      holds promise as a new method of treating large hepatocellular carcinoma.

PMID- 9762993
TI  - Techniques for transjugular intrahepatic portosystemic shunt revision.

PMID- 9762994
TI  - Use of a new percutaneous thrombolytic device for percutaneous removal of biliary
      stones.

PMID- 9762995
TI  - Unenhanced helical CT of ureteral stones: a replacement for excretory urography
      in planning treatment.
AB  - OBJECTIVE: The purpose of this study was to determine whether unenhanced helical
      CT alone can be used for diagnosis and treatment planning of patients with
      obstructing ureteral stones. MATERIALS AND METHODS: Medical records of 100
      patients with ureteral stones and a clearly discernible clinical outcome who had
      undergone unenhanced helical CT were reviewed to determine the number of
      urography procedures and results of excretory urograms performed within 72 hr of
      helical CT. CT scans were then reviewed by two radiologists for six findings: in
      plane stone diameter, z-axis stone diameter, location of stone, periureteral
      stranding, hydronephrosis, and perinephric fluid. Seventy-one patients passed
      stones spontaneously, and 29 patients required intervention including basket
      retrieval, extracorporeal shock-wave lithotripsy, laser lithotripsy, or a
      combination of the three treatments. Data were analyzed to determine those
      findings that correlated with the need for intervention. RESULTS: Five excretory
      urograms were obtained, all of which agreed with findings revealed by CT.
      Excretory urography added no information. CT findings of in-plane diameter (p <
      .001), z -axis diameter (p < .001), and location of stone (p = .003) all
      significantly correlated with the need for intervention. CONCLUSION: Helical CT
      can be used in place of excretory urography to plan treatment of patients with
      flank pain caused by obstructing ureteral stones. Stones that are larger than 5
      mm, located within the proximal two thirds of the ureter, and seen on two or more
      consecutive CT images are more likely to require endoscopic removal, lithotripsy,
      or both.

PMID- 9762996
TI  - Characterization of urinary calculi: in vitro study of "twinkling artifact"
      revealed by color-flow sonography.
AB  - OBJECTIVE: The "twinkling artifact" is a color-flow sonographic artifact
      described behind calcifications and presenting as a random color encoding in the
      region where shadowing would be expected on gray-scale images. Our purpose was to
      study the relationship between this twinkling artifact seen behind urinary stones
      on color-flow sonography and the morphology or biochemical composition of these
      urinary stones. MATERIALS AND METHODS: Forty-seven urinary stones were studied in
      vitro with color-flow sonography. Transmit frequency, color gain, velocity range,
      color filters, focal depth, and depth of field were changed during scanning. The
      twinkling artifact was graded 0 when absent, 1 when present but occupying a
      portion of acoustic shadowing, and 2 when occupying the entire acoustic
      shadowing. Stones were studied under a binocular magnifying glass to characterize
      the surface, and infrared spectrophotometry was used to determine the chemical
      composition. RESULTS: Calculi of calcium oxalate dihydrate and calcium phosphate
      always produced a grade 1 or grade 2 twinkling artifact. Absence of artifact was
      noted only for calcium oxalate monohydrate and urate stones. In 100% of grade 0
      calcium oxalate stones, the monohydrate compound was predominant (>93%). In 100%
      of grade 2 calcium oxalate stones, the dihydrate compound was predominant (>75%).
      For calcium oxalate stones, the surface pattern was correlated with their
      composition. Sensitivity and specificity for absence of artifact, as indicative
      of calcium oxalate monohydrate, were 60% and 83%, respectively, for all stones
      and 56% and 100%, respectively, only for radiopaque stones. CONCLUSION: An in
      vitro relationship exists between the twinkling artifact and the morphology of
      urinary stones. Color-flow sonography could play a role in detecting dense
      calcium oxalate monohydrate calculi, which in turn may help predict
      fragmentability.

PMID- 9762997
TI  - Cystic teratomas of the ovary: diagnostic value of sonography.
AB  - OBJECTIVE: This study was undertaken to determine if the diagnosis of cystic
      teratomas of the ovary can be made by experienced sonologists using only specific
      associated sonographic features. MATERIALS AND METHODS: Two sonologists
      independently reviewed the sonograms of 252 adnexal masses. For each mass, each
      sonologist recorded sonographic features using a standardized checklist, which
      included four descriptions associated with cystic teratomas. From a list of
      diagnostic possibilities, each reviewer chose one specific conclusion, with
      emphasis on achieving the highest combination of sensitivity and positive
      predictive value for any particular diagnosis. The sensitivity, positive
      predictive value, and positive likelihood ratio for the diagnosis of cystic
      teratoma were evaluated for each sonographic finding and for each sonologist's
      interpretation. RESULTS: Of the 252 masses, 74 cystic teratomas were found, 55 of
      which showed two or more associated sonographic features. Each reviewer had a 98%
      positive predictive value with 85% sensitivity for the diagnosis and
      identification of cystic teratomas (positive likelihood ratio = 152). The
      positive predictive value was 100% when an adnexal mass had two or more
      sonographic features associated with dermoid masses. The positive predictive
      value for individual sonographic features associated with dermoid masses was 80%
      for a shadowing echodensity, 75% for regionally bright echoes, 50% for
      hyperechoic lines and dots, and 20% for a fluid-fluid level. CONCLUSION: An
      adnexal mass showing two or more of the sonographic features associated with
      cystic teratomas can be confidently diagnosed as a cystic teratoma.

PMID- 9762998
TI  - Renal lymphoma: spectrum of CT findings and potential mimics.
AB  - Renal lymphoma has a broad spectrum of imaging manifestations. Typical patterns
      of renal lymphoma include multiple renal masses, solitary masses, diffuse
      infiltration, and invasion from contiguous retroperitoneal disease. Isolated
      perirenal disease is probably the most atypical form of renal lymphoma and has a
      variety of appearances, including small curvilinear densities and soft-tissue
      nodules or plaques. In general, the CT diagnosis of renal lymphoma is not
      difficult because most patients already have a known diagnosis of lymphoma.
      Nevertheless, it is important to be familiar with both the typical and the
      atypical manifestations of renal lymphoma because numerous disease processes,
      normal variants, and artifacts may potentially mimic renal lymphoma.

PMID- 9762999
TI  - Kaposi's sarcoma involving a transplanted kidney: CT findings.

PMID- 9763000
TI  - Endovascular occlusion with a new mechanical detachable coil.
AB  - OBJECTIVE: Metallic coils have been used for vascular embolization for many years
      but controlled-release coils have only recently become commercially available.
      Most of these devices are microcoils that were manufactured primarily for the
      packing of intracerebral aneurysms; therefore, they lack radial force and are not
      ideal agents for the occlusion of high-flow lesions such as pulmonary
      arteriovenous malformations (PAVMs). The objective of this study was to review
      our experience with a new detachable coil based on the conventional Gianturco
      Wallace coil. SUBJECTS AND METHODS: The new detachable coil was initially used
      for the treatment of varicocele in 20 patients. Subsequently, the coil was used
      in 48 patients during 90 procedures for the treatment of PAVMs. RESULTS: A total
      of 548 coils were used. Complete occlusion of the testicular vein was achieved in
      all patients with varicocele. Successful occlusion of the PAVM being treated was
      achieved in all patients, and no instances of recanalization were documented in
      any of the patients who returned for follow-up angiography. Forty-one coils had
      to be removed completely from the catheter before detachment because of
      inappropriate size or position. Eight coils failed to detach easily, and six of
      these had to be removed. Most of these device failures were associated with
      kinking of the screw thread mechanism between the coil and the delivery wire.
      CONCLUSION: The Jackson detachable coil allows safer, more accurate, and more
      distal embolization of PAVMs than is possible with nondetachable coils.
      Complications associated with its use have been few.

PMID- 9763001
TI  - Venous rupture complicating hemodialysis access angioplasty: percutaneous
      treatment and outcomes in seven patients.
AB  - OBJECTIVE: To evaluate percutaneous treatment options for preserving hemodialysis
      access after angioplasty-related venous rupture, we retrospectively reviewed the
      charts for all dialysis access angioplasties performed over a 33-month period.
      Seven cases of venous rupture after venous angioplasty were identified (four men
      and three women; mean age, 63.5 years). Treatment included observation only (n =
      1), a second prolonged balloon inflation at the rupture site (n = 2), stent
      insertion (n = 5), and manual graft occlusion (n = 1). Treatment was successful
      in eliminating contrast extravasation in all patients while maintaining immediate
      graft function in six out of seven patients. None of the patients required
      emergent surgical intervention. The mean primary and secondary patency rates of
      the salvaged grafts after intervention were 2.3 and 9.3 months, respectively.
      Five of seven access sites were still patent at the most recent follow-up.
      CONCLUSION: Prolonged balloon inflation or placement of a stent may salvage
      hemodialysis access in most patients after angioplasty-related venous rupture.
      Primary and secondary patency have proven to be satisfactory.

PMID- 9763002
TI  - Effect of anatomic distribution of pulmonary emboli on interobserver agreement in
      the interpretation of pulmonary angiography.
AB  - OBJECTIVE: This study examines the anatomic distribution of emboli on pulmonary
      angiography and attempts to determine the relationship of vessel size to
      interobserver agreement, two factors having important implications in comparing
      pulmonary angiography with cross-sectional imaging for pulmonary embolism.
      MATERIALS AND METHODS: One hundred twenty-five consecutive pulmonary angiograms
      were reviewed retrospectively by three interventional radiologists. Initial
      interpretations were recorded and compared to determine interobserver agreement
      on a per-patient and per-embolus basis. Discordant interpretations were reviewed
      by all radiologists for a consensus interpretation. RESULTS: Unanimous per
      patient agreement occurred in 91% (114/125) of initial interpretations. The
      largest artery containing acute pulmonary embolism was segmental or larger in 24
      patients (83% of patients with acute positive findings, 19% of all patients) and
      subsegmental in only five patients (17% and 4%, respectively). On a per-patient
      basis, initial interobserver agreement averaged 45% and unanimous consensus
      agreement was achieved for 79% of patients having isolated subsegmental pulmonary
      embolism. Consensus readings altered initial per-patient interpretations for 30%
      of patients having only subsegmental pulmonary embolism; per-embolus
      interpretations were altered for 37% of all subsegmental emboli. CONCLUSION:
      Subsegmental emboli occurring as isolated findings are relatively rare.
      Approximately one third of subsegmental emboli and one third of patients having
      isolated subsegmental emboli may be initially misdiagnosed on pulmonary
      angiography. Objections to cross-sectional imaging for pulmonary embolism based
      on the inability to detect subsegmental pulmonary embolism when compared with
      pulmonary angiography should be reexamined with this data in mind.

PMID- 9763003
TI  - Assessment of lung volumes using helical CT at inspiration and expiration:
      comparison with pulmonary function tests.
AB  - OBJECTIVE: This study was designed to determine lung volumes using inspiratory
      and expiratory helical CT with two-dimensional (2D) and three-dimensional (3D)
      postprocessing and to compare the accuracy of those measurements with pulmonary
      function test results. SUBJECTS AND METHODS: Seventy-two patients with suspected
      pulmonary disease underwent unenhanced helical CT (slice thickness, 8 mm; pitch,
      2; increment, 8 mm) at deep inspiration and expiration. Lung volumes were
      determined using either a 2D approach (semiautomatic segmentation; thresholds, 
      1024 and -200 H) or a 3D technique (double-threshold seeded volumes of interest;
      thresholds, -1024 H [lower] and -900, -500, 400, -300, or -200 H [upper]).
      Pulmonary function tests were available for correlation in all cases. RESULTS:
      Using inspiratory helical CT, we underestimated total lung capacity by 12%, which
      had a good correlation (r = .89) with static lung volumes. Volume revealed by
      expiratory helical CT was equivalent to intrathoracic gas volume, which also
      exhibited a good correlation (r = .88). However, using expiratory helical CT, we
      overestimated residual volume by 850 ml with a rather good correlation (r = .77).
      An emphysema index revealed moderate correlation with the relative forced
      expiratory volume in 1 sec (inspiration, r = -.66; expiration, r = -.54), whereas
      the expired volume showed a moderate correlation with the absolute forced
      expiratory volume in 1 sec (r = .65). The 2D approach showed lower absolute
      volumes than the 3D technique (mean, 3.6%; r = .99). In the 3D technique, lower
      upper thresholds led to reduced volumes (170 ml/100 H). CONCLUSION: Inspiratory
      and expiratory helical CT show high correlation with static lung volumes. The 3D
      technique (-1024 to -200 H) is recommended for absolute estimation of lung
      volumes.

PMID- 9763004
TI  - Real-time CT fluoroscopy: usefulness in thoracic drainage.
AB  - OBJECTIVE: The purpose of our study was to review the application of real-time CT
      fluoroscopy in the drainage of localized pleural and mediastinal collections.
      SUBJECTS AND METHODS: Between July 1996 and August 1997, 20 patients with 10
      loculated pleural effusions, two mediastinal fluid collections, and 12 focal
      pneumothoraces were treated using CT fluoroscopy. The patient population was 25
      77 years old and included 14 men and six women. Methods of drainage included
      using a modified Seldinger technique with a guidewire and serial dilators in 10
      patients and a single-stick trocar technique in the remaining 14. Total room
      time, procedure time, and CT fluoroscopy time were recorded. RESULTS: All 24
      collections were successfully evacuated using either real-time or interrupted
      real-time CT fluoroscopy. The real-time capability of CT fluoroscopy proved
      particularly useful for rapid placement of drainage tubes in patients who were
      unable to cooperate with breathing instructions and in patients who had a narrow
      window of access. Average total room time was 65 min. Average procedure time was
      32 min, and average CT fluoroscopy time was 143 sec. CONCLUSION: CT fluoroscopy
      permits rapid drainage of intrathoracic collections. CT fluoroscopy is a
      particularly useful treatment for patients who are unable to perform breath
      holding or in whom access to the drainage site is difficult.

PMID- 9763005
TI  - Imaging of oncologic patients: benefit of combined CT and FDG PET in the
      diagnosis of malignancy.
AB  - OBJECTIVE: The purpose of this study was to assess the benefit of combined CT and
      18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in diagnosing
      malignancy. MATERIALS AND METHODS: The records of 26 patients with intraabdominal
      and intrathoracic neoplasms who underwent CT and FDG PET between January 1995 and
      September 1996 were retrospectively reviewed. Most of these patients had
      inconclusive findings on prior CT for the diagnosis of malignancy. Only sites of
      potential malignant disease were included in the data analysis. Presence or
      absence of malignancy was confirmed by histopathology or follow-up CT. Three
      observers experienced in abdominal imaging used CT findings alone to estimate
      level of suspicion (1 = definitely not malignant to 5 = definitely malignant) for
      primary or recurrent neoplasms (n = 21), distant metastases (n = 25), and
      neoplastic nodal involvement (n = 18). Six weeks later the three observers
      reviewed the same CT examinations supplemented with FDG PET and reestimated
      suspicion of malignancy. Receiver operating characteristic methodology was used
      to analyze the results. Sensitivity, specificity, positive and negative
      predictive values, and accuracy in diagnosis of malignant disease were calculated
      using level 4 (probable malignancy) as the cutoff for the presence of disease.
      RESULTS: The mean area under the receiver operating characteristic curve,
      indicating successful diagnosis of malignancy, was .82 for CT alone and .92 for
      CT with FDG PET (p < .05). The accuracies for diagnosis of primary or recurrent
      neoplasms, distant metastases, and neoplastic nodal involvement were 62%, 68%,
      and 83%, respectively, for CT alone and 81% (p = .06), 88% (p = .03), and 89% (p
      > .25), respectively, for CT with FDG PET. Also, supplemental FDG PET imaging
      improved observer confidence and accuracy in diagnosing recurrent neoplasm in
      four (36%) of 11 patients who had undergone surgery or chemoradiation and in
      diagnosing four (29%) of 14 extrahepatic sites that had potential metastases.
      CONCLUSION: Diagnosis of malignancy in oncologic patients is significantly
      improved when CT is supplemented with FDG PET. Combined imaging is particularly
      helpful in the evaluation of potential recurrence in previously treated patients
      and for diagnosing extrahepatic lesions that may be distant metastases.

PMID- 9763006
TI  - MR lymphangiography in infants, children, and young adults.
AB  - OBJECTIVE: Our objective was to offer a preliminary description of MR
      lymphangiography; its uses and limitations; and its findings in infants,
      children, and young adults. SUBJECTS AND METHODS: Twenty-nine patients underwent
      32 MR lymphangiographic examinations for evaluation of vascular malformations,
      other masses, soft-tissue swelling, gigantism, fluid accumulation, or pain. MR
      lymphangiography was based on a heavily T2-weighted fast spin-echo sequence and a
      maximum-intensity-projection algorithm. We assessed the axial and off-axial
      lymphatic channels in conjunction with MR venography to help differentiate veins
      from lymphatics. Correlation was made with published lymphangiograms and anatomic
      diagrams to assist interpretation and (when available) with histologic specimens
      (n = 11) for validation. RESULTS: Presumed lymphatic channels were seen
      universally, although 14 examinations showed incomplete venous signal
      suppression. Lymphatic channels appeared normal in eight children and in 20 of
      the 21 asymptomatic contralateral limbs. Ten patients had an increased number and
      size of off-axial channels, including seven children with large, diffuse low-flow
      vascular malformations. Enlarged axial and off-axial channels were seen in five
      patients, four of whom had Klippel-Trenaunay syndrome. Six patients, each with an
      extensive hemangioendothelioma, Klippel-Trenaunay syndrome, Gorham syndrome, or
      unilateral body edema, showed absence or interruption of axial channels.
      CONCLUSION: MR lymphangiography appears to be a useful noninvasive technique to
      study superficial and deep lymphatic channels in children with local or diffuse
      vascular lesions or swelling of extremities. Its limitations notwithstanding, the
      technique may offer further insight into the nature of vascular anomalies, may
      direct therapy, and may predict prognosis.

PMID- 9763007
TI  - Echodense spinal subarachnoid space in neonates with progressive ventricular
      dilatation: a marker of noncommunicating hydrocephalus.
AB  - OBJECTIVE: Our purpose was to evaluate the frequency and clinical significance of
      echogenic debris in the spinal subarachnoid space of neonates at risk for
      progressive ventricular dilatation. SUBJECTS AND METHODS: Spinal sonography was
      performed on 15 neonates with severe intracranial hemorrhage (n = 10) or
      bacterial meningitis (n = 5). Spinal sonography also was performed on 16 control
      neonates. Images were analyzed for the presence and location of echogeric debris
      within the thoracolumbar subarachnoid space. Lumbar punctures were performed on
      all 31 neonates, and CSF was analyzed for cell count and protein content. Ten of
      15 neonates required ventricular drainage procedures. RESULTS: Progressive
      ventricular dilatation occurred in 11 of 15 neonates with intracranial hemorrhage
      or meningitis. Echogenic debris was present in the thoracolumbar subarachnoid
      space on spinal sonography in every neonate with progressive ventricular
      dilatation compared with none of the 16 control neonates (p < .0001 by chi-square
      analysis). In addition, the 11 neonates with echogenic subarachnoid space had
      significantly higher protein and RBC contents in the lumbar CSF (p < .04).
      CONCLUSION: Echogenic subarachnoid space revealed by sonography is associated
      with progressive ventricular dilatation after severe intracranial hemorrhage or
      bacterial meningitis and is caused by high protein and RBC contents in the
      subarachnoid space. This finding may be helpful in identifying neonates who will
      not benefit from serial lumbar punctures for treatment of hydrocephalus.

PMID- 9763008
TI  - Cerebral 1H MR spectroscopy and neuropsychologic status of patients with hepatic
      encephalopathy.
AB  - OBJECTIVE: Our objective was to assess the metabolite levels (myo-inositol [ml],
      choline [Cho], creatine [Cr], glutamate or glutamine [Glx], and N-acetyl-L
      aspartate [NAA]) visible on 1H MR spectroscopy in patients with subclinical and
      mild hepatic encephalopathy before and after liver transplantation and to
      correlate these data with the results of neuropsychiatric tests and related
      clinical findings. SUBJECTS AND METHODS: A stimulated-echo sequence was used to
      localize a single voxel in the parietal region. Seventeen patients and 13 healthy
      volunteers were investigated. Nine of the 17 patients also were investigated
      after liver transplantation. A battery of neuropsychologic tests also was
      administered to patients to assess frontal, memory, and motor functions. RESULTS:
      Before liver transplantation, significant reductions in mI:Cr (51%) and Cho:Cr
      (11%) and a significant increase in Glx:Cr (20%) were observed in patients
      compared with the respective ratios in healthy subjects. Patients also were
      significantly impaired on neuropsychologic tests measuring frontal and motor
      performance, but not memory. Impairment on the frontal index showed a significant
      correlation with mI:Cr levels; likewise, performance on the motor index showed a
      significant correlation with serum ammonia levels before transplantation. MR
      spectroscopy after liver transplantation showed changes in the metabolite ratios
      compared with the pretransplantation status. Even though the Glx:Cr ratios
      decreased after transplantation, the mI:Cr ratio remained lower than those of
      healthy subjects. CONCLUSION: The relationship of changes in the metabolite
      ratios recorded from a voxel in the posteromedial parietal lobe to the
      neuropsychologic findings before and after liver transplantation is a major
      finding.

PMID- 9763009
TI  - Usefulness of CT and MR imaging in the diagnosis of acute Wernicke's
      encephalopathy.
AB  - OBJECTIVE: In this study, we analyzed the sensitivity and specificity of CT and
      MR imaging in the diagnosis of acute Wernicke's's encephalopathy. SUBJECTS AND
      METHODS: Three groups of subjects were studied: 15 patients with acute Wernicke's
      encephalopathy; 15 asymptomatic alcoholics; and 15 control subjects. Studies
      included clinical and laboratory examinations as well as CT and MR imaging of the
      brain. RESULTS: On CT scans, two patients with Wernicke's encephalopathy (13%)
      and no asymptomatic alcoholics showed low-density abnormalities in the
      paraventricular regions of the thalamus (p = .2414). On MR imaging, increased T2
      signal of paraventricular regions of the thalamus was observed in seven patients
      (46%) with Wernicke's encephalopathy and one asymptomatic alcoholic (6%) (p <
      .01), and increased T2 signal of periaqueductal regions of the midbrain in six
      patients (40%) with Wernicke's encephalopathy and one asymptomatic alcoholic (6%)
      (p < .05). However, no significant differences were observed in the prevalence of
      mamillary body shrinkage between alcoholics with Wernicke's encephalopathy (six
      [40%]) and asymptomatic chronic alcoholics (four [27%]). The sensitivity of MR
      imaging in revealing evidence of this disease was 53% and the specificity, 93%.
      CONCLUSION: MR imaging is useful in confirming the diagnosis of acute Wernicke's
      encephalopathy. However, the absence of abnormalities on MR imaging does not
      exclude this diagnosis. CT proved not useful in the diagnosis of Wernicke's
      encephalopathy.

PMID- 9763010
TI  - The hippocampus: normal anatomy and pathology.
AB  - The hippocampus is a complex and fascinating region of the brain that has
      enormous clinical significance. Specifically, small imaging abnormalities may
      cause major symptoms. We believe that the detection of these lesions will be
      improved if imaging clinicians have an organized reference that facilitates
      identification of the cellular zones that comprise the hippocampus.

PMID- 9763011
TI  - MR imaging in a patient with homocystinuria.

PMID- 9763012
TI  - Helical CT for initial imaging of pulmonary embolus.

PMID- 9763013
TI  - Circumscribed lesions seen at screening mammography.

PMID- 9763014
TI  - Transvaginal sonography in postmenopausal women with bleeding.

PMID- 9763015
TI  - More on standards of care.

PMID- 9763016
TI  - More on informed consent.

PMID- 9763017
TI  - Re: Chest radiography after placement of internal jugular central venous access
      devices.

PMID- 9763018
TI  - More on sonographic features in the differentiation of fibroadenoma and invasive
      ductal carcinoma.

PMID- 9763019
TI  - Aortic dissection versus penetrating aneurysm.

PMID- 9763020
TI  - Heartburn redux.

PMID- 9763021
TI  - Insignificance of small loculated pneumothoraces after core biopsies of
      peripheral lung lesions using the Temno biopsy needle.

PMID- 9763022
TI  - A rare cause of respiratory failure: Echinococcus of the pulmonary artery.

PMID- 9763023
TI  - Disseminated Bartonella henselae (cat-scratch disease): appearance of multifocal
      osteomyelitis with MR imaging.

PMID- 9763024
TI  - Three-dimensional sonography in diagnosing trisomy 18.

PMID- 9763025
TI  - Isolated uterine relapse in a child with acute lymphoblastic leukemia.

PMID- 9763026
TI  - An unusual sonographic finding in Caroli's disease.

PMID- 9763027
TI  - Frozen section of thyroid? Just say no.

PMID- 9763028
TI  - Alpha-L-fucose: a potentially critical molecule in pathologic processes including
      neoplasia.
AB  - Alpha-L-fucose is a 6-carbon deoxyhexose that is commonly incorporated into human
      glycoproteins and glycolipids. It is found at the terminal or preterminal
      positions of many cell-surface oligosaccharide ligands that mediate cell
      recognition and adhesion-signaling pathways. These include such normal events as
      early embryologic development and blood group recognition and pathologic
      processes including inflammation, infectious disease recognition, and neoplastic
      progression. Fucosylated oligosaccharide ligands mediate cell-cell adhesion
      through binding to cell-surface selectins (calcium-dependent binding proteins)
      and calcium-dependent interactions with other cell-surface carbohydrate
      counterligands. A number of fucose-containing "natural ligands" are common to
      inflammatory and malignant cell processes. We review evidence that alpha-L-fucose
      is critically important for cell-cell and cell-matrix adhesion in a variety of
      normal and pathologic processes, particularly neoplasia. Current results suggest
      that alpha-L-fucose provides the essential structure that enables carbohydrate
      ligands to bind to selectins and to carbohydrate counterligands and thereby alter
      cellular homeostasis.

PMID- 9763029
TI  - Bcl-2 oncoprotein positivity and high MIB-1 (Ki-67) proliferative rate are
      independent predictive markers for recurrence in prostate carcinoma.
AB  - Predicting the clinical behavior of prostate carcinoma can be difficult; one
      approach is to identify molecular prognostic markers. We evaluated proliferative
      rate (MIB-1 antibody) and expression of bcl-2, p53, and retinoblastoma (pRB)
      proteins, which have cell cycle-related functions, in 208 consecutive radical
      prostatectomy specimens. Values were correlated with histopathologic parameters
      (Gleason tumor score, tumor amount, capsule invasion, and involvement of surgical
      margins, seminal vesicles, or lymph nodes) and with recurrence-free survival (4
      year median follow-up). A high MIB-1 proliferative rate was associated with all
      of the measured histopathologic parameters, p53 overexpression with tumor amount,
      and pRB expression with positive lymph nodes. pRB and p53 expression levels were
      not associated with differences in recurrence-free survival. A high MIB-1
      proliferative rate and bcl-2 positivity were associated with increased
      recurrence, both considered individually, and also independently and additively
      when examined together and with the most predictive histopathologic factors
      (Gleason tumor score and seminal vesicle involvement). MIB-1 proliferative rate
      and bcl-2 positivity may prove to be useful markers for poor prognosis in
      prostate carcinoma.

PMID- 9763030
TI  - Histochemical analysis of mucous cells of congenital adenomatoid malformation of
      the lung: insights into the carcinogenesis of pulmonary adenocarcinoma expressing
      gastric mucins.
AB  - Adenocarcinomas expressing gastric mucins often are accompanied by ectopic
      gastric mucosa or pyloric metaplasia. We have previously described mucinous
      bronchioloalveolar carcinoma (mucinous BAC) producing gastric mucins. In the lung
      tissue, mucous cells seemingly similar to gastric mucous cells are present in
      congenital adenomatoid malformation (CAM). We assessed 26 cases of CAM
      morphologically and histochemically. Mucous cells were detected in 12 of 26
      cases. These mucous cells displayed papillary growth in cystic spaces and
      proliferated along alveolar walls. Mucous cells in the papillary, configuration
      stained with galactose oxidase cold thionine Schiff reaction, and those in
      indented portions stained with paradoxical concanavalin A stain in all 8 cases
      and with pepsinogen II in 5 of 8 cases, which were available for histochemical
      analysis. Pepsinogen I was negative. Mucous cells in CAM were identical to those
      of pyloric mucosa and could be considered candidates for the origin of mucinous
      BAC producing gastric mucins.

PMID- 9763032
TI  - Four-color flow cytometric immunophenotypic determination of peripheral blood
      CD4+ T-lymphocyte counts: a comparison of validity and cost-effectiveness with a
      two-color method.
AB  - The clinical usefulness of monitoring CD4+ T-lymphocyte counts in patients
      infected with HIV is now well established. The need for accurate, rapid, and cost
      effective methods for making these determinations is evident. Recent technologic
      advances have allowed for the development of a system for the determination of
      CD4+ T-lymphocyte counts by simultaneous 4-color flow cytometry. A new 4-color 2
      tube flow cytometric method for analyzing CD4+ T-lymphocyte subsets in whole
      blood was compared with a standard 2-color 5-tube method. The new method provides
      results almost identical to those of the well-established 2-color method used in
      our clinical laboratory. Statistical analyses indicate very low variability in
      CD4+ counts between the 2 methods, strongly supporting the usefulness of this new
      procedure. In addition, the 4-color procedure provides a 15% reduction in the
      materials cost per test compared with the 2-color method, as well as a marked
      reduction in the time expenditure of flow cytometry technologists.

PMID- 9763031
TI  - Comparison of intraoperative cytology with frozen sections in the diagnosis of
      thyroid lesions.
AB  - We retrospectively studied the usefulness of intraoperative cytology (IOC) and
      frozen section (FS) in the rapid diagnosis of 68 thyroid lesions. In 14 cases of
      papillary thyroid carcinoma, IOC correctly diagnosed 13 cases, while FS correctly
      diagnosed 11 cases. There was no significant difference in sensitivities, and
      both methods had similar specificities. In 21 cases of colloid nodule, IOC was
      slightly more sensitive than FS; IOC correctly diagnosed 16 cases, while FS
      correctly diagnosed 15 cases. However, the specificity of IOC was only 71%, but
      was 98% for FS. Of 17 follicular adenomas, FS diagnosed 16 as follicular
      neoplasms and misdiagnosed only 1 as a colloid nodule. By contrast, IOC
      misdiagnosed 9 follicular adenomas as colloid nodules, most of which were
      macrofollicular variants with abundant colloid. Of 11 follicular carcinomas, FS
      diagnosed all as follicular neoplasms, while IOC misdiagnosed 3 as colloid
      nodules. While IOC is not as accurate as FS in the diagnosis of colloid nodules
      and follicular neoplasms, it is highly sensitive and specific in the diagnoses of
      papillary carcinoma and performance of the technique is rapid and easy. In an
      intraoperative setting, IOC is a useful adjunct to FS in screening thyroid
      nodules for the presence of papillary carcinoma.

PMID- 9763033
TI  - Lymphoid lesions of the gastrointestinal tract: a histologic, immunophenotypic,
      and genotypic analysis of 49 cases.
AB  - The diagnosis of gastrointestinal (GI) lymphoid infiltrates can be challenging
      when based only on conventional microscopic assessment. When marked cytologic
      atypia is present, a diagnosis of malignant neoplasm is readily made; however,
      the distinction between a low-grade malignant neoplasm and a reactive process is
      much more difficult. If unfixed tissue is available, immunohistologic or
      genotypic methods that are usually aimed at defining B-lymphocytic monotypism can
      be applied. However, paraffin-embedded tissue has generally been deemed
      unsuitable for these techniques. We assessed the value of a panel of
      immunohistochemical stains and a seminested polymerase chain reaction (PCR) for
      the analysis of lymphoid infiltrates in routinely processed GI biopsy specimens
      from 49 archival cases, including morphologically benign, indeterminate, and
      overtly malignant lesions. Clinical outcome was used as the retrospective
      diagnostic standard; end points were death (of lymphomatous disease or otherwise)
      and clinical evidence of lymphoma. According to light microscopic criteria, 19
      cases were classified as benign, 17 as malignant, and 13 as atypical.
      Immunophenotyping correctly identified 28 of 31 benign and 14 of 18 malignant
      lesions (7 cases had an indeterminate immunoprofile). Genotypic analysis
      correctly identified 12 of 18 malignant and 29 of 31 benign lesions, but spurious
      monoclonal bands were produced by PCR amplification of 2 of the latter 31 cases.
      No single technique exists for correct categorization of all paraffin-embedded
      specimens of GI lymphoid infiltrates. We recommend a sequential approach to the
      use of available diagnostic modalities.

PMID- 9763034
TI  - A cutaneous agranular CD2- CD4+ CD56+ "lymphoma": report of two cases and review
      of the literature.
AB  - We report 2 cases of agranular CD2- CD4+ CD56+ non-Hodgkin lymphoma in which skin
      seemed to be the primary site. A 21-year-old woman's initial symptom was a skin
      nodule on the right cheek. She also had tumors in the nasopharynx, and the bone
      marrow subsequently became involved. No lymphadenopathy was present. She
      experienced complete remission after dose-intensified therapy with
      cyclophosphamide, hydroxydaunomycin, vincristine [Oncovin], and prednisone
      (CHOP), but the disease relapsed in the central nervous system 6 months later. An
      81-year-old man experienced an 11-month history of skin nodules in the left
      forearm. On admission, he had a bone marrow infiltration of lymphoma cells. He
      died of pneumonia during chemotherapy. The malignant cells of the 2 patients had
      similar morphologic features, with a monocytoid nucleus and no cytoplasmic
      granules. The cells in both cases showed a unique phenotype: CD2-, CD3-, CD4+,
      CD8-, CD13-, CD14-, CD34-, CD16-, CD56+, CD57-, HLA-DR-positive. Staining for
      peroxidase and alpha-naphthyl butyrate esterase was negative. The T-cell receptor
      beta, gamma, delta, IgH, kappa, lambda genes were of germ line configurations.
      The DNA of Epstein-Barr virus was not detected from the bone marrow cells by
      polymerase chain reaction. Only 3 other cases with similar phenotypes have been
      reported; all had skin lesions. Although the origin of these cells remains
      unknown, we propose that this is a distinct clinicopathologic entity.

PMID- 9763035
TI  - Cocaine and cocaethylene binding to human milk.
AB  - The binding of cocaine and its ethyl analog, cocaethylene, to human milk was
      studied using equilibrium dialysis at 4 degrees C. For cocaine, a low-affinity,
      high-capacity binder was noted (equilibrium constant of association, Ka, 3.12 x
      10(3) L/mol; concentration of binding sites, B0, 3.85 x 10(-4) mol/L), as well as
      a very low affinity, high-capacity binder (Ka, 7.54 x 10(2) L/mol; B0, 1.42 x 10(
      3) mol/L). For cocaethylene, 2 low-affinity, high-capacity binders were
      suggested: a stronger (Ka, 3.79 x 10(3) L/mol; B0, 3.27 x 10(-4) mol/L) and a
      weaker (Ka, 1.84 x 10(3) L/mol; B0, 8.91 x 10(-4) mol/L) binder The low-affinity,
      high-capacity binder for cocaine and cocaethylene seems to be albumin, while the
      weaker nonspecific binding may be due to lipids. Up to 55% of cocaine and up to
      61% of cocaethylene were bound to milk; such binding, coupled with the lower pH
      of milk (6.9) relative to that of serum (7.4), may enhance the mammary secretion
      of these 2 basic drugs, having important consequences for the nursing infant.

PMID- 9763036
TI  - Evaluation of a rapid homogeneous method for direct measurement of high-density
      lipoprotein cholesterol.
AB  - We evaluated the performance of a direct Liquid N-geneous HDL-C assay (N-HDL;
      Genzyme Diagnostics, Cambridge, Mass) and compared it with a Centers for Disease
      Control and Prevention (CDC) modified reference procedure (M-REF) and
      phosphotungstic acid (PTA) precipitation method in patients with
      normotriglyceridemia (triglyceride level, <400 mg/dL) and hypertriglyceridemia
      (triglyceride level, > or =400 mg/dL). Excellent intra-assay and interassay
      coefficients of variation were obtained (<2.0%) using the N-HDL assay. The N-HDL
      and PTA assays correlated well with M-REF in normotriglyceridemic samples. In
      hypertriglyceridemic samples, however, the N-HDL method exhibited better
      correlation with M-REF than the PTA assay. In addition, compared with M-REF, the
      mean absolute percentage bias of N-HDL was lower than the PTA assay in
      normotriglyceridemic (4.9% vs 5.8%) and hypertriglyceridemic (5.4% vs 12.9%)
      samples. Hemolysis, ascorbic acid, and bilirubin did not interfere with the N-HDL
      assay. On the basis of these findings, the N-HDL assay compares favorably with
      the modified CDC reference method and seems superior to the PTA assay. It also
      has the advantage of being suited for complete automation and, thus, would prove
      useful in large clinical laboratories.

PMID- 9763037
TI  - Prospective study of serum protein capillary zone electrophoresis and
      immunotyping of monoclonal proteins by immunosubtraction.
AB  - Capillary zone electrophoresis and immune adsorption were evaluated for
      identification of serum protein abnormalities and immunotyping of monoclonal
      proteins. A 7-capillary, electrophoresis instrument and solid phase
      immunosubtraction reagents were used in a prospective study of 1,518 patients.
      Serum protein electrophoresis was performed by agarose gel electrophoresis and
      capillary electrophoresis and interpreted with regard to identification of
      abnormalities consistent with monoclonal gammopathies. The agarose gel
      electrophoresis had a sensitivity and specificity of 91% and 99%, respectively,
      whereas capillary electrophoresis gave results of 95% and 99%. Immunotyping of
      the monoclonal proteins was performed by immunofixation and immunosubtraction.
      Capillary electrophoresis was more sensitive than agarose gel electrophoresis for
      the identification of monoclonal proteins in serum. In addition, the
      immunosubtraction method seems technically simpler and more automated than
      immunofixation and represents a useful additional approach for immunotyping
      monoclonal proteins.

PMID- 9763038
TI  - A conflict of interest?

PMID- 9763039
TI  - Human sensitivity vs automation.

PMID- 9763040
TI  - The blood supply in 1984.

PMID- 9763041
TI  - Routine ultrasound is the method of choice for dating pregnancy.

PMID- 9763042
TI  - Misoprostol for all?

PMID- 9763043
TI  - Continuing medical education: an opportunity for bringing about change in
      clinical practice.

PMID- 9763044
TI  - The reproductive system after childhood cancer.

PMID- 9763045
TI  - Folates in the periconceptional period: are women getting enough?
AB  - OBJECTIVE: To examine the prevalence of folic acid supplementation prior to
      conception and in the first trimester of pregnancy, and to identify
      sociodemographic variables associated with the use of supplements. DESIGN:
      Observational study. SETTING: District general hospital in the south in England.
      POPULATION: Nine hundred and sixty-three randomly selected pregnant nulliparous
      caucasian women recruited from May 1994 to February 1996 inclusive. METHODS:
      Questionnaire administered at approximately 16 weeks gestation. MAIN OUTCOME
      MEASURES: Intakes of supplemental folic acid before conception and during
      pregnancy. RESULTS: 31.5% (303/963) (95% CI 28.5-34.4) of pregnant women reported
      using supplements containing folic acid prior to conception. The proportion using
      pre-conceptional folic acid increased by approximately 1% per month during the 22
      months of the study. 38.1% (367/962) (35 1 to 41.2) of women began taking folic
      acid only after the confirmation of pregnancy, and this proportion appeared
      constant over time. Young age, smoking and low educational attainment were
      statistically significant predictors of failure to use folic acid both before and
      during pregnancy. CONCLUSIONS: Use of folic acid before conception in nulliparous
      women is much higher than the 2% to 3% reported in earlier studies of all
      pregnant women, and appears to be increasing. However, many women still only
      begin taking folic acid after conception, despite current health education
      strategies. New approaches, focusing on women who are currently least likely to
      take folic acid those who are young, are of low educational backgrounds, and are
      smokers - may now be required. Given the inevitably of unplanned pregnancies,
      efforts must also be made to increase the currently static uptake of folic acid
      immediately after the confirmation of pregnancy.

PMID- 9763046
TI  - Choosing options for ultrasound screening in pregnancy and comparing cost
      effectiveness: a decision analysis approach.
AB  - OBJECTIVE: To compare the cost effectiveness of different programmes of routine
      antenatal ultrasound screening to detect four key fetal anomalies: serious
      cardiac anomalies, spina bifida, Down's syndrome and lethal anomalies, using
      existing evidence. DESIGN: Decision analysis was used based on the best data
      currently available, including expert opinion from the Royal College of
      Obstetricians and Gynaecologists, Working Party and secondary data from the
      literature, to predict the likely outcomes in terms of malformations detected by
      each screening programme. SETTING: Results applicable in clinics, hospitals or GP
      practices delivering antenatal screening. MAIN OUTCOME MEASURE: The number of
      cases with a 'target' malformation correctly detected antenatally. RESULTS: There
      was substantial overlap between the cost ranges of each screening programme
      demonstrating considerable uncertainty about the relative economic efficiency of
      alternative programmes for ultrasound screening. The cheapest, but not the most
      effective, screening programme consisted of one second trimester ultrasound scan.
      The cost per target anomaly detected (cost effectiveness) for this programme was
      in the range 5,000 pound silver-109,000, pound silver but in any 1000 women it
      will also fail to detect between 3.6 and 4.7 target anomalies. CONCLUSIONS: The
      range of uncertainty in the costs did not allow selection of any one programme as
      a clear choice for NHS purchasers. The results suggested that the overall
      allocation of resources for routine ultrasound screening in the UK is not
      currently economically efficient, but that certain scenarios for ultrasound
      screening are potentially within the range of cost effectiveness reached by
      other, possibly competing, screening programmes. The model highlighted the
      weakness of available evidence and demonstrated the need for more information
      both about current practice and costs.

PMID- 9763048
TI  - Partogram action line study: a randomised trial.
AB  - OBJECTIVE: To assess the effect of three different partograms on caesarean
      section and maternal satisfaction. DESIGN: Prospective randomised clinical trial.
      SETTING: Regional teaching hospital in North West of England. PARTICIPANTS: Nine
      hundred and twenty-eight primigravid women with uncomplicated pregnancies who
      presented in spontaneous labour at term. INTERVENTIONS: The women were randomised
      to have their progress of labour recorded on a partogram with an action line 2, 3
      or 4 hours to the right of the alert line. If the progress reached the action
      line, a diagnosis of prolonged labour was made. Prolonged labour was managed
      according to the standard ward protocol. MAIN OUTCOME MEASURES: Primary:
      Caesarean section rate and maternal satisfaction; secondary: need for
      augmentation, duration of labour, analgesia, cord blood gas analysis, postpartum
      haemorrhage, number of vaginal examinations, Apgar score and admission to special
      care baby unit. RESULTS: Caesarean section rate was lowest when labour was
      managed using a partogram with a 4-hour action line. The difference between the 3
      and 4-hour partograms was statistically significant (OR 1 8, 95% CI 1.1-3.2),
      but the difference between 2 and 4 hours was not (OR 1.4, 95% CI 0.8-2.4). The
      women in the 2-hour arm were more satisfied with their labour when compared to
      the women in the 3-hour (P < 00001) and 4-hour (P <00001) arm. CONCLUSION: Our
      data suggest that women prefer active management of labour. It is possible that
      partograms which favour earlier intervention are associated with higher caesarean
      section rate. As the evidence on which to base the choice of partograms remains
      inconclusive further research is required.

PMID- 9763047
TI  - A randomised placebo controlled trial of oral misoprostol in the third stage of
      labour.
AB  - OBJECTIVE: To compare oral misoprostol 400 microg with placebo in the routine
      management of the third stage of labour. DESIGN: A double-blind placebo
      controlled trial. Setting The labour ward of an academic hospital in
      Johannesburg, South Africa with 7000 deliveries per annum. PARTICIPANTS: Low-risk
      women expected to deliver vaginally. METHODS: Women in labour were randomly
      allocated to receive either misoprostol 400 microg orally or placebo after the
      birth. Conventional oxytocics were given immediately if blood loss was thought to
      be more than usual. Postpartum blood loss in the first hour was measured by
      collection in a special flat plastic bedpan. Side effects were recorded. MAIN
      OUTCOME MEASURES: Measured blood loss > or = 1000 ml within the first hour after
      birth. Use of additional oxytocics. RESULTS: The groups were well matched.
      Measured blood loss > or = 1000 ml occurred in 15/250 (6%) after misoprostol and
      23/250 (9%) after placebo (relative risk 0.65; 95% confidence interval 0.35
      1.22). The difference may have been reduced by the greater use of conventional
      oxytocics in the placebo group, which was statistically significant for
      intravenous oxytocin infusion (2.8% vs 8.4%, relative risk 0.33, 95% confidence
      interval 0.14-0.77). Shivering was more common in the misoprostol group (19% vs
      5%, relative risk 3.69; 95% confidence interval 2.05-6.64). CONCLUSIONS:
      Shivering has been shown in this study to be a specific side effect of
      misoprostol administered orally in the puerperium. No serious side effects were
      noted. Misoprostol shows promise as a method of preventing postpartum
      haemorrhage. Because of the potential benefits for childbearing women,
      particularly those in developing countries, further research to determine its
      effects with greater certainty should be expedited.

PMID- 9763049
TI  - Maternal intensive care and near-miss mortality in obstetrics.
AB  - OBJECTIVE: To determine the level of near-miss maternal mortality and morbidity
      due to severe obstetrical complications or maternal disease in a tertiary
      maternity hospital. DESIGN: Retrospective review. SETTING: A free-standing
      maternity hospital delivering 5500 infants per year. METHODS: The information
      coded in the perinatal database concerning women who had required transfer for
      critical care to a general hospital was reviewed for the 14 year period 1980 to
      1993. The complications necessitating transfer and the specialised consultants
      and services required were noted. RESULTS: Over 14 years there were 76,119 women
      delivered with two maternal deaths (2.6/100,000). Fifty-five women required
      transfer for critical care (0.7/1000). The main reasons for transfer were
      hypertensive disease (25%), haemorrhage (22%) and sepsis (15%). Transfer to an
      intensive care unit was required by 80%, and the remainder were transferred to
      specialised medical or surgical units. Twenty different specialist groups were
      consulted. The 55 patients spent 280 days in critical care and 464 days hospital
      after-care (mean 13 days, range 3-92). CONCLUSION: A review of near-miss maternal
      mortality helps delineate the continuing threats to maternal health and the type
      of support services most commonly required.

PMID- 9763050
TI  - Severe acute maternal morbidity: a pilot study of a definition for a near-miss.
AB  - OBJECTIVE: To test the application of a clinical definition of severe acute
      maternal morbidity. DESIGN: A one-year prospective descriptive multi-centre
      study. SETTING: Kalafong and Pretoria Academic hospitals, catering for the
      delivery of indigent women in the Pretoria Health Region. METHODS: A 'near-miss'
      describes a patient with an acute organ system dysfunction, which if not treated
      appropriately, could result in death. The case notes of women fitting this
      definition and all maternal deaths were analysed and compared. OUTCOME MEASURE:
      Determine the primary obstetric factors and the organ systems that failed.
      Identification of episodes of sub-standard care and missed opportunities. Results
      One hundred and forty-seven near misses and 30 maternal deaths were identified.
      The commonest reasons for a near-miss were: emergency hysterectomy in 42 women
      (29%); severe hypotension in 40 (27%); and pulmonary oedema in 24 (16%). The most
      common initiating obstetric conditions were hypertension in 38 women (26%);
      haemorrhage in 38 (26%); and abortion or puerperal sepsis in 29 (20%). The
      primary obstetric factors amongst the maternal deaths were: hypertension (33%);
      sepsis (27%); and maternal medical diseases (17%) in 10, 8 and 5 women
      respectively. Sub-standard care was identified in 82 cases. Breakdown in the
      health care administration was identified in 33, and patient-orientated missed
      opportunities on 34 occasions. CONCLUSION: The definition of severe acute
      maternal morbidity identified nearly five times as many cases as maternal death.
      This definition allows for an effective audit system of maternal care because it
      is clinically based, the definition is robust and the cases identified reflect
      the pattern of maternal death.

PMID- 9763052
TI  - The impact of rubella immunisation on the incidence of rubella, congenital
      rubella syndrome and rubella-related terminations of pregnancy in South
      Australia.
AB  - OBJECTIVES: To describe the impact of rubella immunisation on the incidence of
      rubella, congenital rubella syndrome and rubella-related terminations of
      pregnancy in South Australia, and to identify factors associated with a re
      emerging problem. DESIGN AND METHODS: A population-based descriptive study using
      data from South Australian notifications of disease, births and terminations of
      pregnancy, the rubella immunisation programme, antenatal rubella antibody
      screening and paediatric hospital case records. SETTING: South Australia
      (population 1.48 million people; 20,000 births per year). MAIN OUTCOME MEASURES:
      Incidence of rubella (age-sex specific), congenital rubella syndrome and rubella
      related terminations of pregnancy; antenatal rubella sero-positive rates; rubella
      immunisation uptake rates. RESULTS: Rubella notification rates in 1990-1996 were
      significantly higher for males than females for ages 15-34 years. There were five
      cases of congenital rubella syndrome notified in 1980-1996 compared with at least
      20 confirmed or compatible cases in 1965-1979. Rubella-related terminations of
      pregnancy are now rare, with the last termination for maternal rubella being in
      1993. The antenatal rubella sero-positive rate in 1995 was 96.7%, but was
      significantly lower among Asian women born overseas (78.6% among those 30 years
      or older). Vaccination uptake rates in schoolgirls decreased between 1990 and
      1994 (91.2% to 86.9%). CONCLUSIONS: Since the introduction of rubella
      immunisation, the incidence of rubella infection among women of reproductive age,
      and of rubella-related terminations, has fallen. Congenital rubella syndrome has
      not been notified since 1990 but its risk persists with a recent increase in
      rubella notifications, a fall in school immunisation rates, a relatively low
      antenatal sero-positive rate among older Asian women born overseas and the trend
      towards giving birth at older ages. Effective immunisation programmes must be
      maintained, particularly in schools and for young children and migrant women.

PMID- 9763051
TI  - Does an early postnatal check-up improve maternal health: results from a
      randomised trial in Australian general practice.
AB  - OBJECTIVES: To investigate whether a visit to a general practitioner one week
      after discharge results in less depression, increased breastfeeding rates,
      improved patient wellbeing, fewer physical problems and greater satisfaction with
      general practice care than the traditional six week postnatal check-up. DESIGN: A
      randomised controlled trial. SETTING: Rural and metropolitan Victoria, Australia.
      Population Women giving birth at one rural and one metropolitan hospital between
      February and December 1995 inclusive. METHODS: All women received a letter and
      appointment date to see a general practitioner for a check-up: the intervention
      group for one week after hospital discharge, the control group for six weeks
      after birth. A mail-out survey was conducted at three and six months after birth,
      including Edinburgh Postnatal Depression Scale and Short Form 36. RESULTS:
      1017/1407 (72.3%) women giving birth at participating hospitals were eligible for
      the trial: 683 (67.2%) gave informed consent. The average response rate to postal
      follow up at three and six months was 67.5%. No significant differences were
      found between the groups in: Edinburgh Postnatal Depression and Short Form 36
      scores; number of problems; breastfeeding rates; or satisfaction with general
      practitioner care. Women in the intervention group were less likely to attend for
      their check-up (76.4% vs 88.4%; P = 0.001), more likely to discuss labour and
      birth at their check-up (OR= 1.77, 95% CI 1.17-2.68), less likely to have a
      vaginal examination (OR = 0.51; 95%, CI 0.34-0.77) or pap smear (OR = 0.34; 95%
      CI = 0.22-0.52) at their check; more likely to report difficulties with low milk
      supply (OR= 1.72; 95% CI = 1.12-2.66) and adjusting to the demands of a new baby
      (OR = 1.76; 95% CI 1.13 2.74), more likely to talk to a general practitioner
      about their baby (68.2% vs 58.0%; P=0.02) and less likely to consult a hospital
      doctor about their baby (7.3% vs 14.0%, P = 0.02). CONCLUSIONS: To make
      clinically important improvements in maternal health more is required than early
      postnatal review.

PMID- 9763053
TI  - Neonatal mortality amongst Scottish preterm singleton births (1985-1994).
AB  - OBJECTIVE: To provide a valid estimate of singleton neonatal mortality based on
      birthweight and gestational age at delivery. DESIGN: Record linkage of maternity
      data and neonatal mortality data. SETTING: Scotland, UK. POPULATION: All
      singleton preterm deliveries from 24 to 36 weeks inclusive between 1985 and 1994.
      MAIN OUTCOME MEASURE: Neonatal death. RESULTS: There were 625,646 liveborn
      singleton deliveries over the study period, of which 33,912 were preterm (5.4%).
      The overall neonatal mortality in the preterm group was 41/1000 and the data have
      been presented by both gestational age and birthweight. The neonatal mortality
      rate fell with advancing gestation from 795/1000 live births at 24 weeks to
      9/1000 live births at 36 weeks and was higher at the extremes of birthweight for
      a given gestational age. There was a significant increase in the proportion of
      babies delivered iatrogenically over the study period (chi test for trend P <
      0.001). CONCLUSION: This is the largest recent series to consider neonatal
      mortality using both birthweight and gestational age. These figures will be of
      use in obstetric management when elective preterm delivery is considered, and for
      providing prognostic guidance following preterm delivery.

PMID- 9763054
TI  - Preterm and term births of small for gestational age infants: a population-based
      study of risk factors among nulliparous women.
AB  - OBJECTIVE: To study risk factors for small for gestational age (SGA) infants by
      gestational age among nulliparous women and to estimate mortality rates among SGA
      and appropriate-for-gestational-age (AGA) infants by gestational age. DESIGN: A
      population-based study from the Swedish Medical Birth Register. Setting Sweden
      1992 1993. POPULATION: Liveborn singleton infants to nulliparous women (n =
      96,662). MAIN OUTCOME MEASURES: Crude and adjusted odds ratios of risk factors
      for SGA by gestational age. Rates of neonatal and postneonatal mortality.
      RESULTS: Older maternal age (> or = 30 years) was foremost associated with
      increased risks of very and moderately preterm SGA (> or = 32 weeks and 33-36
      weeks, respectively), but also with term SGA (> or = 37 weeks). Risks of SGA
      increased with decreasing maternal height at all gestational ages. Smoking
      increased the risks of moderately preterm and term SGA. Short maternal education
      increased the risk of preterm SGA and low pre-pregnancy body mass index slightly
      increased the risk of term SGA. Pre-eclampsia and essential hypertension foremost
      increased the risk of very preterm SGA (OR = 40.5 and 32.4, respectively) and
      moderately preterm SGA (OR = 17.4 and 10.6, respectively), but also increased the
      risk of term SGA. Neonatal and postneonatal mortality rates of SGA infants were
      substantially influenced by gestational age, and mortality rates were
      consistently higher among preterm SGA infants compared with AGA infants.
      CONCLUSIONS: Risk factors for SGA and mortality rates among SGA infants vary by
      gestational age. A subdivision of risk factors by gestational age adds knowledge,
      particularly about risks of preterm SGA, where the highest rates of mortality
      were observed.

PMID- 9763055
TI  - Is cystic ovarian endometriosis an asymmetric disease?
AB  - OBJECTIVE: To investigate whether asymmetry exists in the left- and right-handed
      distribution of ovarian cystic lesions in a large series of women with
      endometriosis. DESIGN: Retrospective evaluation of a case series. SETTING:
      Tertiary care and referral academic centre for the study and treatment of
      endometriosis. POPULATION: A total of 1054 consecutive women undergoing first
      line surgical treatment for endometriosis in an eight-year period. METHODS: Data
      were collected on indication for the intervention, age at surgery, parity and
      disease stage as well as side and size of ovarian endometriomas. MAIN OUTCOME
      MEASURE: Frequency of left- and right-sided ovarian endometriomas. RESULTS:
      Histologically confirmed endometriotic ovarian cysts were present in 561 women,
      which were on the left side in 255 instances, on the right in 148, and bilateral
      in 158. In the patients with unilateral endometriomas, the observed proportion of
      left cysts (255/403, 63%; 95% confidence interval, 58% to 68%) was significantly
      different from the expected proportion of 50%, (chi2(1), 28.41, P<0.001).
      Including also the bilateral endometriotic cysts gave a total of 413/719 (57%)
      left-sided and 306/719 right-sided endometriomas. The magnitude of these
      proportions did not vary appreciably during the eight years considered. The
      difference in proportion of left- and right-sided endometriotic cysts was
      virtually similar in subgroups of women with different indications for surgery.
      Cyst side was not related to age, parity or cyst diameter. CONCLUSIONS: The
      finding of a lateral asymmetry in the occurrence of ovarian endometriotic cysts
      is compatible with the anatomical differences of the left and right hemipelvis
      and supports the menstrual reflux theory.

PMID- 9763057
TI  - Vaginal misoprostol alone is effective in the treatment of missed abortion.

PMID- 9763056
TI  - Do routine antibiotics after loop diathermy excision reduce morbidity?
AB  - OBJECTIVE: To evaluate whether routinely giving an antibiotic after loop
      diathermy excision of the cervical transformation zone reduced post-operative
      vaginal loss. DESIGN: Prospective, randomised, double-blind placebo controlled
      parallel study. PARTICIPANTS: Five hundred women undergoing loop diathermy
      excision in a colposcopy clinic. INTERVENTION: Administration of either ofloxacin
      400 mg (2x200 mg) once daily for 5 days or an identical placebo. MAIN OUTCOME
      MEASURE: Vaginal loss, assessed using a pictorial chart. RESULTS: No significant
      difference in post-operative vaginal loss was found. CONCLUSION: Routine
      antibiotic prophylaxis after loop diathermy excision is not justified.

PMID- 9763058
TI  - Pregnancy and homozygous beta thalassaemia major.
AB  - Nine pregnant women with homozygous beta-thalassaemia major followed a strict
      transfusion regimen to maintain their haemoglobin level > 10 g/dl. One pregnancy
      was terminated because of concern about desferrioxamine teratogenicity and
      another ended in miscarriage at 11 weeks. All other women were delivered by
      elective caesarean section between 37 and 38 weeks. There were no obstetric
      complications or perinatal deaths.

PMID- 9763059
TI  - Influence of chemotherapy for gestational trophoblastic disease on subsequent
      pregnancy outcome.
AB  - The aim of this study was to determine the influence of cytotoxic chemotherapy on
      subsequent reproductive performance. Details of post-treatment reproductive
      intent and outcome were requested from 1211 survivors registered at The Charing
      Cross Hospital gestational trophoblastic disease centre; a response rate of 96%
      was achieved. Seven hundred and twenty-eight women had tried to become pregnant;
      607 reported at least one live birth, 73 conceived but had not registered a live
      birth, and 48 did not conceive. No differences were apparent between the 392
      women who received methotrexate as single agent chemotherapy and the 336 treated
      with multi-agent chemotherapy. Women who had registered a live birth were younger
      (P < 0.0001) and the duration of follow up was significantly less among those who
      did not achieve pregnancy at all (P < 0.0003). A higher than expected rate of
      caesarean section and stillbirth was recorded. The chemotherapy protocols used by
      this unit have minimal impact on the subsequent ability to reproduce.

PMID- 9763060
TI  - Vaginal delivery following combined pelvic renal and pancreatic transplant.

PMID- 9763061
TI  - Retrievable inferior vena cava filter for thrombolic disease in pregnancy.

PMID- 9763062
TI  - Retrievable inferior vena cava filter for thrombolic disease in pregnancy.

PMID- 9763063
TI  - Routine ultrasound dating has not been shown to be more accurate than the
      calendar method.

PMID- 9763064
TI  - A study of the quality of perinatal autopsy in the former Northern region.

PMID- 9763065
TI  - Magnesium sulphate: a review of clinical pharmacology applied to obstetrics.

PMID- 9763066
TI  - Magnesium sulphate: a review of clinical pharmacology applied to obstetrics.

PMID- 9763067
TI  - Renal dysplasia: the risks and consequences of leaving dysplastic tissue in situ.

PMID- 9763068
TI  - Early experience with intraoperative cavernous nerve stimulation with penile
      tumescence monitoring to improve nerve sparing during radical prostatectomy.
AB  - OBJECTIVES: To determine if intraoperative stimulation of the cavernous nerves
      while monitoring changes in penile tumescence to map the course of these nerves
      would result in an improvement in nerve sparing and erectile function after
      radical prostatectomy. METHODS: Patients were eligible for this pilot study if
      they were undergoing a radical prostatectomy and were candidates for a nerve
      sparing approach. Erectile function was assessed by patient self-reporting and
      questionnaire before surgery and by patient self-reporting periodically 12 months
      after surgery. A cavernous nerve stimulator and tumescence-monitoring device was
      used during radical prostatectomy to identify the course of the cavernous nerves
      and guide the surgeon in avoiding nerve damage. Patients were monitored for any
      evidence of complications and/or adverse events for 1 year from time of surgery.
      RESULTS: Twenty-six patients were recruited to the trial. Nerve stimulation and
      tumescence monitoring was performed in 23 patients. Twenty-one of 23 patients
      demonstrated a tumescence response to intraoperative nerve stimulation. Nineteen
      of 21 patients reported erectile function preoperatively. Seventeen (89%) of 19
      patients demonstrated a tumescence response during surgery. Sixteen (94%) of the
      17 patients who demonstrated a response to nerve stimulation and for whom the
      surgery was guided by the tumescence response reported the ability to have
      erections after surgery. No side effects due to the use of the device were
      reported. Only 3 (12%) of 25 patients had positive margins confined to the
      lateral margin and/or apex whose modifications associated with nerve sparing
      could conceivably have altered margin status. CONCLUSIONS: These clinical data
      suggest that an intraoperative tumescence response to cavernous nerve stimulation
      may guide the surgeon in preserving cavernous nerves and improving erectile
      function after radical prostatectomy.

PMID- 9763069
TI  - Laparoscopic renal cryoablation: initial clinical series.
AB  - OBJECTIVES: To present the technique and short-term results of retroperitoneal
      laparoscopic renal cryoablation. METHODS: Ten patients underwent laparoscopic
      renal cryoablation of 11 exophytic renal tumors ranging in size from 1.5 to 3 cm
      identified on computed tomography. Tumors were located at the upper (3), middle
      (5), or lower (3) pole of the kidney. Three patients had a solitary kidney. A 3
      port retroperitoneal laparoscopic approach was used to create renal cryolesions.
      Puncture cryoablation was performed with a 4.8-mm cryoprobe. Real-time,
      endoscopic, steerable, color Doppler ultrasound was used to monitor the evolving
      cryolesion. All patients have completed a minimum follow-up of 3 months (mean
      5.5, range 3 to 9). RESULTS: Cryoablation was technically successful in all 10
      patients (11 tumors). Under ultrasound guidance, the ice ball was intentionally
      created up to 1 cm beyond the tumor edge with the aim of achieving negative
      margins. Mean surgical time was 2.4 hours, cryoablation (double freeze-thaw) time
      12.9 minutes, cryoprobe tip temperature -186 degrees C, and blood loss 75 mL.
      Systemic temperature remained unaltered. Hospital stay was less than 23 hours in
      9 of 10 patients. Follow-up magnetic resonance imaging at 1 day and 1, 2, and 3
      months identified the punched-out, nonenhancing, spontaneously resorbing, renal
      cryolesion. Follow-up biopsies of the cryoablated tumor site were negative for
      cancer in the 3 patients who have undergone the biopsy. CONCLUSIONS: The initial
      series of laparoscopic renal cryoablation is presented. The retroperitoneoscopic
      approach, by avoiding the peritoneal cavity, minimizes the chances of the bowel
      coming in contact with the evolving cryolesion, and the potential sequelae
      thereof. Laparoscopic renal cryoablation is currently developmental and long-term
      data are awaited. Nevertheless, it is potentially an attractive addition to
      available nephron-sparing surgical techniques.

PMID- 9763070
TI  - Single-dose oral ciprofloxacin versus placebo for prophylaxis during transrectal
      prostate biopsy.
AB  - OBJECTIVES: To determine whether antimicrobial prophylaxis could prevent
      infections after transrectal needle biopsy of the prostate using automated biopsy
      devices. METHODS: We conducted a prospective, randomized, double-blind,
      multicenter trial in which a total of 537 patients received either oral
      ciprofloxacin 500 mg or placebo before transrectal needle biopsy of the prostate.
      Repeated urine cultures and urinalysis were obtained at 2 to 6 days after biopsy
      and 9 to 15 days after biopsy. The primary determinant of efficacy was
      bacteriologic response (bacteriuria [more than 10(4) colony-forming units
      (CFU)/mL] versus no bacteriuria) at the 9- to 15-day follow-up evaluation.
      RESULTS: Two hundred twenty-seven (84%) of 269 ciprofloxacin patients and 230
      (86%) of 268 placebo patients were valid for efficacy analysis in which a mean of
      four biopsies was performed. Six ciprofloxacin-treated (3%) and 19 placebo
      treated (8%) patients had bacteriuria (more than 10(4) CFU/mL) after the
      procedure (P = 0.009). Six ciprofloxacin recipients (3%) and 12 placebo
      recipients (5%) had clinical signs and symptoms of a urinary tract infection
      (UTI) (P = 0.15). In addition, no ciprofloxacin-treated patients compared with 4
      placebo-treated patients (2%) were admitted to the hospital for febrile UTI after
      the procedure. Ciprofloxacin reduced the expected net costs of treating
      infectious complications after biopsy by $23 per patient for an overall annual
      savings of $68,195 in the five study groups when compared with placebo.
      CONCLUSIONS: Single-dose oral ciprofloxacin reduced bacteriuria after biopsy
      compared with placebo in patients undergoing transrectal prostatic biopsy and
      provided an economic advantage. In addition, this study establishes the actual
      rate of bacteriuria after transrectal needle biopsy of the prostate without
      antibiotic prophylaxis to be 8% with a clinical rate of UTI of 5% and a
      hospitalization rate of 2%.

PMID- 9763071
TI  - Laser therapy of squamous cell dysplasia and carcinoma of the penis.
AB  - OBJECTIVES: To analyze the influence of etiologic factors and practical issues
      regarding the merits, limitations, and long-term results of aggressive laser
      treatment of premalignant and malignant squamous cell lesions of the penis.
      METHODS: Preparation of genital skin with 5% acetic acid and mapping biopsies of
      lesions and the surrounding field-of-change were performed in 52 men evaluated
      and subsequently treated with laser during a 10-year period. Most men (81%) were
      or had been smokers, and many (46%) had female sexual partners infected with
      human papillomavirus. Carbon dioxide laser was used for low-stage lesions;
      potassium-titanylphosphate/532 or neodymium:yttrium-aluminum-garnet laser was
      used for more histologically advanced lesions. Not only the lesions but also the
      entire human papillomavirus-induced field-of-change was treated. Circumcision was
      performed simultaneously in 28 previously uncircumcised patients. RESULTS: All
      lesions demonstrated aceto-whitening and histologic changes of human
      papillomavirus infection. Human papillomavirus DNA was detected in 93.5% of the
      specimens from 31 patients studied. Of the 52 patients, 22 (42%) had dysplastic
      premalignant penile intraepithelial neoplasia, and the remaining 30 (58%) had
      squamous cell carcinoma. Forty-four patients were available for follow-up from 12
      to 117 months (average 58). Overall, 5 patients (11.4%) experienced a recurrence:
      3 were successfully re-treated with laser, and 2 patients underwent partial
      penectomy, 1 of whom with squamous cell carcinoma Stage T2 died of metastatic
      disease. CONCLUSIONS: Aggressive laser therapy of the visible lesions and of the
      entire dysplastic premalignant field-of-change produces excellent cosmetic
      results. The entire penis and, therefore, its full sexual functional potential
      are preserved. The low rate of local recurrence over the long term in all but
      deeply invasive (T2) lesions compares favorably with the outcome of other, more
      conventional therapies. Irrespective of therapeutic approach, close and long-term
      surveillance of all patients and counseling for their sexual partners are
      mandatory.

PMID- 9763073
TI  - Detection of adrenal and retroperitoneal masses in a general health examination
      system.
AB  - OBJECTIVES: To investigate the detection rate of adrenal and retroperitoneal
      masses other than kidney diseases in a general health examination system.
      METHODS: From May 1991 through February 1996, 41,357 subjects participated in the
      general health examination system in our hospital. Approximately 80% of
      participants were 40 to 59 years old. For all participants, transabdominal
      ultrasound (US) was performed by five expert examiners using an Aloka SSD-650
      with a 3.5-MHz convex-type transducer. When US revealed abnormal lesions on the
      adrenal gland and in the retroperitoneal space, we recommended that participants
      be examined with computed tomography (CT), with a slice width of 5 mm. RESULTS:
      Forty-three participants (0.1%) had abnormal findings on US. Of the 28 of those
      who underwent CT examination to confirm the lesions, 12 had adrenal and
      retroperitoneal masses. The detection rate was 0.029% of total participants and
      42.9% of those who underwent CT examination. Clinical diagnoses were primary
      aldosteronism (1), preclinical Cushing syndrome (2), nonfunctioning
      adrenocortical tumor (5), pheochromocytoma (1), ganglioneuroma (1), adrenal cyst
      (1), and retroperitoneal neurinoma (1). False-positive results were dominant on
      the left side of the body (right 3, left 13). A deformed or accessory spleen (3),
      a cyst on the upper pole of the kidney (2), bowel air (2), and a pancreatic cyst
      (1) were misdiagnosed as adrenal lesions on US. CONCLUSIONS: The low detection
      rate of adrenal and retroperitoneal masses by US does not support screening for
      the diseases in healthy subjects. However, if it is done as part of a general
      health examination, examiners should attentively observe not only the kidneys but
      also the adrenal gland and retroperitoneal space because clinically important
      diseases may be detected.

PMID- 9763072
TI  - Retroperitoneal and pelvic extraperitoneal laparoscopy: an international
      perspective.
AB  - OBJECTIVES: To assess technical preferences and current practice trends of
      retroperitoneal and pelvic extraperitoneal laparoscopy. METHODS: A questionnaire
      survey of 36 selected urologic laparoscopic centers worldwide was performed.
      RESULTS: Twenty-four centers (67%) responded. Overall, 3988 laparoscopic
      procedures were reported: transperitoneal approach (n = 2945) and
      retroperitoneal/extraperitoneal approach (n = 1043).
      Retroperitoneoscopic/extraperitoneoscopic procedures included adrenalectomy (n =
      74), nephrectomy (n = 299), ureteral procedures (n = 166), pelvic lymph node
      dissection (n = 197), bladder neck suspension (n = 210), varix ligation (n = 91),
      and lumbar sympathectomy (n = 6). Mean number of total laparoscopic procedures
      performed in 1995 per center was 41 (range 5 to 86). Major complications occurred
      in 49 (4.7%) patients and included visceral complications in 26 (2.5%) patients
      and vascular complications in 23 (2.2%). Open conversion was performed in 69
      (6.6%) patients, electively in 41 and emergently in 28 (visceral injuries, n =
      16; vascular injuries, n = 1 2). Retroperitoneoscopy/extraperitoneoscopy is
      gaining in acceptance worldwide: in 1993, the mean estimated ratio of
      transperitoneal laparoscopic cases versus retroperitoneoscopic/
      extraperitoneoscopic cases per center was 74:26; however, in 1996 the ratio was
      49:51. CONCLUSIONS: Retroperitoneoscopy and pelvic extraperitoneoscopy are
      important adjuncts to the laparoscopic armamentarium in urologic surgery. The
      overall major complication rate associated with
      retroperitoneoscopy/extraperitoneoscopy was 4.7%.

PMID- 9763074
TI  - Nephron-sparing surgery for renal angiomyolipoma.
AB  - OBJECTIVES: Angiomyolipoma (AML) is a benign renal tumor that may require
      treatment because of associated local complications. The present study was
      undertaken to evaluate the efficacy of nephron-sparing surgery (NSS) in the
      management of renal AML, with respect to the long-term preservation of renal
      function and absence of tumor recurrence. METHODS: From 1980 to 1997, 27 patients
      underwent NSS for treatment of renal AML. The clinical presentation, surgical
      approach, and outcome in these patients were analyzed. Surgical treatment for
      renal AML was indicated because of associated symptoms, size of 4.5 cm or
      greater, and/or suspicion of renal malignancy. RESULTS: In symptomatic patients
      (52%) the most common presenting signs or symptoms were pain (50%),
      retroperitoneal hemorrhage or shock (43%), hematuria (36%), hypertension (7%),
      palpable mass (7%), and anemia (7%). Two patients had tuberous sclerosis. Fifteen
      patients had a solitary functioning kidney (group I), 6 patients had an impaired
      contralateral kidney (group II), and 6 patients had a normal contralateral kidney
      (group III). All operations were performed in situ. There were no operative
      deaths. All operated kidneys functioned postoperatively, and no patient required
      dialysis. The mean postoperative serum creatinine level in groups I, II, and III
      was 1.81, 0.98, and 0.97 mg/dL, respectively. No patients have developed
      recurrent AML, related symptoms, or required dialysis with follow-up to 177
      months (median 39). CONCLUSIONS: When surgical treatment for renal AML is
      indicated, NSS can be performed with a high success rate even in patients with a
      very large tumor involving a solitary kidney.

PMID- 9763075
TI  - Partial nephrectomy: alternative treatment for selected patients with renal cell
      carcinoma.
AB  - OBJECTIVES: To analyze the experience and the results of partial nephrectomy in a
      single institution over the last 10 years in order to optimize patient selection
      and minimize morbidity. METHODS: This is a retrospective chart review of 64
      patients (mean age 56.6 years, range 18 to 88; 43 men, 21 women) who underwent 66
      partial nephrectomies at the Brigham and Women's Hospital between 1987 and 1997.
      Preoperatively, 62% of the patients had no symptoms, whereas 38% had pain and/or
      hematuria. The indications were elective in 23 patients, solitary kidney in 28
      (14 with bilateral asynchronous tumor), bilateral synchronous tumor in 7, von
      Hippel-Lindau disease with normal contralateral kidney in 3, lymphoma in 3, and
      other indications in 2 patients. Surgery was performed for solid or indeterminate
      renal mass suspected of being renal cell carcinoma in 58 patients. RESULTS: The
      most common final pathologic diagnosis was renal cell carcinoma in 47 procedures.
      One or more complications occurred after 18 procedures (15 with solitary kidney
      and 3 in patients with normal contralateral kidney) or 27% of the patients. The
      most common complication was an increased creatinine level (two times the
      baseline), occurring in 10 procedures (15.1%). Transfusion was necessary in 37 of
      66 procedures (56%), and the mean blood loss was 836 cc (range 100 to 3200).
      Regarding renal function, 85% of the patients had a minimal increase in
      creatinine of less than 0.5 mg/dL after surgery (all patients with a normal
      contralateral kidney are in this group); 3 patients required either temporary (n
      = 1) or permanent (n = 2) dialysis. Other complications are also described. The
      mean length of stay among 65 patients was 6.5 days (range 3 to 14). The
      differences between length of stay, blood loss, and tumor size were statistically
      significant between the solitary kidney group and the elective indications group
      (P < 0.001). CONCLUSIONS: Nephron sparing surgery is feasible and relatively safe
      in patients with a normal contralateral kidney. Awareness of potential
      complications should aid in the selection of appropriate patients for this
      procedure.

PMID- 9763076
TI  - Pleurotomy, pneumothorax, and surveillance during living donor
      nephroureterectomy.
AB  - OBJECTIVES: To determine the incidence of and risk factors associated with
      pneumothorax after donor nephroureterectomy and to determine the utility of
      postoperative chest roentgenography. METHODS: A retrospective review was made of
      130 living donor nephroureterectomies performed at one institution (Yale-New
      Haven Hospital) using an extraperitoneal flank incision. RESULTS: Incidental
      pleurotomy occurred in 11 cases (8.5%). Rib resection was associated with
      pleurotomy. Patient age, sex, and side of operation were not associated with
      pleurotomy. Ten (91 %) of the 11 cases were identified intraoperatively. One
      unrecognized pneumothorax was identified postoperatively with chest
      roentgenography; no specific intervention was necessary. CONCLUSIONS: The
      extraperitoneal flank incision poses a significant risk for pneumothorax. Most
      pneumothoraces will be recognized intraoperatively. No adverse effects were noted
      secondary to pneumothorax.

PMID- 9763078
TI  - Use of magnetic resonance urography.
AB  - OBJECTIVES: Magnetic resonance urography (MRU) is a new technique that uses
      heavily weighted T2 coronal images with fat suppression pulse. Urine appears
      white on MRU, resembling an intravenous urogram (IVU). Contrast agents are not
      necessary. This study describes the use of MRU in the diagnosis and treatment of
      patients with hematuria. METHODS: One hundred six patients with microscopic or
      gross hematuria and 6 normal volunteers underwent MRU between 1992 and 1995. A
      modified, heavily weighted T2 technique with intravenous administration of
      furosemide and ureteral compression was used. Thirty-two patients had other
      imaging techniques as well for comparison. RESULTS: MRU provided high-resolution
      images in almost all cases; 73 (69%) had a normal MRU. Significant findings in
      the 33 patients with abnormalities included renal cysts in 17 (51%), renal cell
      carcinoma in 6 (18%), transitional cell carcinoma in 5 (15%), ureteropelvic
      junction obstruction in 3 (9%), and stones causing obstruction in 6 (18%). Five
      patients with renal failure also had good visualization of the entire urinary
      tract. MRU was comparable to other imaging modalities except in identifying
      nonobstructing calculi. CONCLUSIONS: MRU provides an alternative to conventional
      imaging of the urinary tract, especially in those patients who have
      contraindications to ionizing radiation and contrast agents. Improvements in
      resolution, technique, and cost have to be addressed before it can be used
      regularly in urologic practice.

PMID- 9763077
TI  - Prognostic factors, recurrence, and survival in transitional cell carcinoma of
      the upper urinary tract: a 30-year experience in 252 patients.
AB  - OBJECTIVES: To review a large single-center experience of patients treated for
      upper tract transitional cell carcinoma (TCC) with extended follow-up in order to
      identify patterns of recurrence, assess patient outcomes, and determine the
      impact of traditional prognostic factors. METHODS: We reviewed 252 patients
      treated surgically for upper tract TCC with a median follow-up of 64 months. Most
      patients (77%) underwent nephroureterectomy, whereas 17% were treated with a
      parenchymal sparing approach. Traditional prognostic factors including age, sex,
      tumor stage, grade, location, and type of surgical treatment were analyzed with
      respect to disease recurrence and survival. RESULTS: Disease relapse occurred in
      67 patients (27%) at a median time of 12.0 months. Recurrences were local in the
      retroperitoneum (9%), the bladder (51%), remaining upper tract (18%), or distant
      in the lung, bone, or liver (22%). The 6 patients with local relapse were among
      the 73 patients with pT3 or pT4 tumors, and all died of TCC at a median time from
      diagnosis of 37 months. Significant prognostic factors for recurrence by
      univariate analysis were tumor grade (P = 0.0014) and stage (P = 0.0001). On
      multivariate analysis, only tumor stage (P = 0.017) and treatment modality (P =
      0.020) were predictors of recurrence. Actuarial 5-year disease-specific survival
      rates by primary tumor stage were 100% for Ta/cis, 91.7% for T1, 72.6% for T2,
      and 40.5% for T3. Patients with primary Stage T4 tumors had a median survival of
      6 months. Although tumor stage and grade correlated with disease-specific
      survival on univariate analysis, only patient age (P = 0.042) and stage (P =
      0.0001) were significant on multivariate analysis with the type of surgical
      procedure performed approaching significance (P = 0.0504). CONCLUSIONS: Primary
      tumor stage and surgical procedure performed (radical versus parenchymal sparing)
      are important predictors of disease recurrence. Patient age and tumor stage were
      the only predictors of disease-specific survival on multivariate analysis with
      the type of surgical procedure approaching significance. Radical
      nephroureterectomy achieves excellent local control even in the setting of
      locally advanced (pT3 or T4) disease. The major clinical feature in this setting
      is distant failure, and the development of effective systemic therapy is needed
      to improve the outcome in these patients.

PMID- 9763079
TI  - Use of ureteroscopy and holmium:YAG laser in patients with bleeding diatheses.
AB  - OBJECTIVES: To assess the safety and efficacy of ureteroscopy and holmium laser
      in patients with known bleeding diatheses and upper tract calculi or transitional
      cell carcinoma (TCC). METHODS: Eight patients with stone disease and 1 patient
      with upper tract TCC were treated ureteroscopically with the holmium laser. The
      mean age was 58.3 years (range 42 to 74). Six patients were receiving Coumadin,
      with a mean international normalized ratio (INR) of 2.1 (normal INR less than
      1.1). Two patients were thrombocytopenic, and 1 had von Willebrand's disease.
      None of the bleeding diatheses were corrected before surgery. Semirigid or
      flexible ureteroscopes were used to access the ureter or intrarenal collecting
      system. The holmium laser was used to fragment calculi or ablate tumor. RESULTS:
      Only 1 patient had a postoperative bleeding complication related to the
      procedure, involving an episode of oliguria secondary to a small ureteral clot.
      This cleared without surgical intervention. Another patient developed an episode
      of epistaxis after administration of ketorolac for pain. Six of 7 patients who
      underwent laser fragmentation for calculi were stone free on follow-up
      intravenous urogram at 1 month, and no tumor recurrence was noted in the patient
      with TCC (follow-up of 4 months). CONCLUSIONS: Ureteroscopy allowed excellent
      access to all regions of the upper tracts, and holmium laser fragmentation of
      calculi or ablation of tumor was effective in managing each particular problem.
      Use of the holmium laser with ureteroscopic access provides a safe and acceptable
      combination for treating upper tract pathology in patients with uncorrected
      bleeding diatheses. As a result, these patients can avoid added costs of extended
      hospital stay and risks associated with transfusions.

PMID- 9763080
TI  - Validation of a harmonized Spanish version of the IPSS: evidence of equivalence
      with the original American scale. International Prostate Symptom Score.
AB  - OBJECTIVES: To validate the use in Spain of a linguistically harmonized Spanish
      version of the International Prostate Symptom Score (IPSS Sp), and to compare it
      with the original American scale (IPSS Am). METHODS: Validity and reliability
      were studied in 59 patients with benign prostatic hyperplasia (BPH) (age >50
      years) and 68 control subjects without BPH (age 18 to 49 years). Construct
      validity was assessed by correlating IPSS Sp scores with the EuroQol-5D (EQ-5D),
      the Psychological General Well-Being Index (PGWBI), and item 8 (quality of life)
      of the IPSS. Discriminatory power was assessed by calculating the area under the
      receiver operating characteristic (ROC) curve. Reliability was evaluated using
      the test-retest method, and internal consistency was assessed using Cronbach's
      alpha. Sensitivity to change was expressed as the effect size in preintervention
      versus postintervention scores in 26 additional patients with BPH (age >50 years)
      who underwent transurethral resection of the prostate. RESULTS: Correlations of
      the IPSS Sp were -0.07 to 0.36 with EQ dimensions; -0.29 with the EQ visual
      analogue scale score; 0.14 to 0.41 with PGWBI dimensions; and 0.72 with item 8 of
      the IPSS. ROC area was 0.95 +/- 0.02 (standard error). Using a cutoff point of 7,
      sensitivity was 83% and specificity was 98%. Test-retest reliability was 0.92 and
      Cronbach's alpha was 0.79. Mean preoperative and postoperative IPSS Sp scores
      were 25.56 and 8.48, respectively (P < 0.001 ). Overall effect size was 2.52.
      These results are similar to those of the original American scale. CONCLUSIONS:
      This Spanish translation of the IPSS is valid, reliable, and sensitive to
      clinical change and has demonstrated equivalent psychometric properties to the
      original American instrument. Scores obtained with the two instruments can
      therefore be reliably compared and aggregated when statistically appropriate.

PMID- 9763081
TI  - Interstitial cystitis in men.
AB  - OBJECTIVES: To determine the personal characteristics, the mode of presentation,
      the duration of the delay in diagnosis, the number of misdiagnoses, the means to
      achieve diagnosis, and previous treatment provided for a group of men with
      interstitial cystitis (IC). METHODS: A chart review of 29 men diagnosed with IC
      at our facility from 1988 to 1996 was performed. Basic demographic data,
      historical information, laboratory findings, and endoscopic and biopsy results
      were tabulated. RESULTS: IC in this series of men was diagnosed at a mean age of
      67.3 years. There was approximately a 4-year diagnostic lag between presentation
      and diagnosis. The most common prior erroneous diagnoses were prostatitis in 48%
      and benign prostatic hypertrophy (BPH) in 38% of the men. Ulcers were encountered
      cystoscopically in about 70% and biopsy specimens uniformly showed nonspecific
      chronic cystitis at the time of diagnosis. CONCLUSIONS: IC should be considered
      in the differential diagnosis of voiding disorders accompanied by irritative
      symptoms and pelvic pain in older men. The diagnosis should be especially
      considered in men who are refractory to the usual treatments for BPH and
      prostatitis. Cystoscopy and bladder distention under anesthesia provided the most
      useful objective information in our hands. Biopsy is useful to rule out
      inflammatory cancer but adds little to the diagnosis of IC.

PMID- 9763082
TI  - Position-related changes in voiding dynamics in men.
AB  - OBJECTIVES: To investigate by urodynamic study position-related changes in
      uroflowmetry and postvoid residual urine volume (PVR) in men because altered
      bladder function in the supine position may be a predisposing factor for urinary
      tract infections in the institutionalized elderly. METHODS: Two healthy men, 34
      and 59 years of age and living at home, and 53 nursing home residents (mean age
      71.8 years, range 46 to 92) were evaluated with uroflowmetry in the standing and
      recumbent positions (lying on the left or right side); corresponding PVRs were
      measured by transabdominal ultrasonic bladder scanning. The two healthy men were
      monitored longitudinally with multiple recordings in both voiding positions, and
      the nursing home residents were subjected to two observations: one measurement of
      the variable parameters in either position. Differences were considered to be
      significant at P < 0.05. RESULTS: The 34-year-old man performed 51 3 flows (368
      standing and 145 recumbent). The mean of all the peak flow rates in the upright
      (28.2 +/- 4.2 mL/s) versus the recumbent (16.8 +/- 4.1 mL/s) position revealed a
      highly significant difference (P = 0.0001). Sixteen urinary flows and
      corresponding PVRs were completed by this subject in either voiding position. The
      difference between PVRs in the standing (13.1 +/- 14.7 mL) versus recumbent (15.3
      +/- 17.5 mL) position was not statistically significant. The 59-year-old man
      completed 156 flows (128 standing and 28 recumbent). A highly significant
      difference was noted between the mean of all peak flows in the upright (18.9 +/-
      4.1 mL/s) versus recumbent (12.6 +/- 2.0 mL/s) position (P = 0.0001). Thirty
      seven urinary flows and corresponding PVRs were completed by this individual (10
      PVRs were determined after voiding in the standing and 27 after voiding in the
      recumbent position). No significant difference was noted between PVRs in the
      standing (24.6 +/- 34.4 mL) versus recumbent (16.5 +/- 60.0 mL) position. In the
      nursing home residents, the difference between the mean peak flow rates in the
      standing (14.5 +/- 8.6 mL/s) versus recumbent (12.4 +/- 6.7 mL/s) position also
      reached statistical significance (P = 0.0084). The difference between PVRs in the
      standing (60.5 +/- 125.6 mL) versus recumbent (84.8 +/- 186.2 mL) position barely
      reached statistical significance (P = 0.0497). CONCLUSIONS: The urinary flow rate
      decreases in the recumbent position. Bedridden residents may be predisposed to
      urinary tract infections because of alterations in voiding dynamics in the supine
      position. This area needs further study.

PMID- 9763083
TI  - A prostate gland volume of more than 75 cm3 predicts for a favorable outcome
      after radical prostatectomy for localized prostate cancer.
AB  - OBJECTIVES: Both the benign and malignant prostatic epithelial components of the
      prostate gland contribute to the serum prostate-specific antigen (PSA) level.
      Therefore, for a given PSA, the presence of benign hyperplastic prostate tissue
      (BHPT) may indicate a lower cancer burden. This study was performed to assess the
      impact of varying amounts of BHPT on PSA failure free (bNED) survival after
      radical prostatectomy for localized prostate cancer. METHODS: Cox regression
      multivariable analyses were performed to assess the ability of the clinical
      stage, PSA, biopsy Gleason score, and prostate gland volume to predict time to
      postoperative PSA failure in 885 patients. RESULTS: In addition to the PSA (P <
      0.0001), biopsy Gleason score of 8 to 10 (P < 0.0001) and of 7 (P = 0.05), and
      clinical Stage T2c,3a (P < 0.0001) and T2b (P = 0.0016), the prostatectomy
      prostate gland volume (P < 0.0001) was a significant predictor of time to
      postoperative PSA failure. Patients with a prostatectomy prostate gland volume
      greater than 75 cm3 had a 100% 4-year bNED survival and favorable pathologic
      characteristics (pathologic Stage T2, 85%; prostatectomy Gleason score 6 or less,
      78% and 7, 22%; and negative margins, 95%) despite a preoperative PSA of 10 to 20
      ng/mL and more than 20 ng/mL in 28% and 13% of these men, respectively. In 75% of
      these cases, lead time bias because of PSA driven repeat biopsies provided an
      explanation. CONCLUSIONS: Lead time bias because of PSA driven repeat biopsy
      accounted for the high 4-year bNED survival and favorable pathologic findings for
      most patients who had prostate cancer coexisting in a prostate gland comprised of
      BHPT and a total gland volume in excess of 75 cm3. An additional explanation is
      needed, however, for the remaining patients.

PMID- 9763084
TI  - Prostate-specific membrane antigen expression is greatest in prostate
      adenocarcinoma and lymph node metastases.
AB  - OBJECTIVES: Prostate-specific membrane antigen (PSMA) is an integral membrane
      protein highly specific for the prostate. PSMA may be clinically useful for
      predicting outcome in patients with prostate cancer. We compared the expression
      of PSMA in prostate adenocarcinoma and lymph node metastases in a large series of
      patients with node-positive cancer. METHODS: We studied 232 patients with node
      positive adenocarcinoma who underwent bilateral pelvic lymphadenectomy and
      radical retropubic prostatectomy at the Mayo Clinic between 1987 and 1992.
      Immunohistochemistry was performed using monoclonal antibody 7E11-5.3 directed
      against PSMA. For each case, the percentage of immunoreactive cells in benign
      prostate tissue, adenocarcinoma, and lymph node metastases was estimated in 10%
      increments. Intensity was recorded using a scale of 0 to 3 (0 = no staining, 3 =
      highest). RESULTS: Cytoplasmic immunoreactivity for PSMA was observed in all
      cases in benign epithelium and cancer, and most lymph node metastases. The number
      of cells stained was lowest in benign epithelium; cancer and lymph node
      metastases were similar (46.2% +/- 27.5% versus 79.3% +/- 18.5% versus 76.4% +/-
      26.1%, respectively; all pairs P < 0.05). Intensity of staining was greatest in
      primary cancer and lowest in lymph node metastases. CONCLUSIONS: PSMA is
      expressed in benign prostatic epithelium and primary cancer in all cases and in
      98% of cases with lymph node metastases. Expression of PSMA was greatest in
      primary cancer for both percentage and intensity of immunoreactive cells. PSMA
      expression allows the identification of benign and malignant prostatic epithelium
      and may be a potentially valuable marker in the treatment of patients with
      prostate cancer.

PMID- 9763085
TI  - Efficacy of one dose fluoroquinolone before prostate biopsy.
AB  - OBJECTIVES: To demonstrate the efficacy of a simple preparation for prostate
      biopsy (PBX) and to determine its potential cost savings. METHODS: One hundred
      fifty consecutive PBXs were performed using a Fleet enema and a single oral dose
      (300 mg) of ofloxacin as the pre-PBX preparation. RESULTS: Of the 150 PBXs we
      performed, only 1 (0.67%) patient developed a urinary tract infection.
      CONCLUSIONS: A simple and inexpensive pre-PBX preparation proved to be successful
      in preventing infectious complications and is presented as a potential model for
      inclusion in clinical pathways for diagnosing adenocarcinoma of the prostate.

PMID- 9763086
TI  - Variability in patient preparation for prostate biopsy among American urologists.
AB  - OBJECTIVES: To assess the variability in patient preparation for prostate biopsy
      (PBX) among practicing American urologists. METHODS: A survey was sent to 900
      practicing American urologists randomly selected by the American Urological
      Association computer files. The survey asked about their pre-PBX protocol.
      RESULTS: Approximately 63% (568 of 900) of the surveys were returned and showed
      considerable differences in pre-PBX protocol among those urologists. The pre-PBX
      regimen included prophylactic antibiotics in 98.6% and a cleansing rectal enema
      in 81%. Eleven different antibiotics were used, with 20 different doses and 23
      different timing-duration regimens. CONCLUSIONS: The pre-PBX preparation is not
      standardized among American urologists.

PMID- 9763087
TI  - Relationship of ultrasound staging and bilateral biopsy positivity to outcome in
      stage T1c prostate cancer treated with radiotherapy.
AB  - OBJECTIVES: The strict definition of Stage T1c prostate cancer is that the tumor
      is not palpable on digital rectal examination (DRE) or seen on imaging studies
      such as ultrasound. The inclusion of ultrasound imaging was brought about without
      an understanding of the relationship between ultrasound upstaging and prognosis.
      We have also noticed that in clinical practice, treatment decisions are made on
      the basis of the finding of bilateral versus unilateral biopsy positivity. The
      objectives in this study were to determine the prognostic significance of
      upstaging by transrectal ultrasound (TRUS) to uT2 or uT3, and unilateral versus
      bilateral biopsy positivity in patients with Stage T1c cancer as determined by
      DRE (DRE-Stage T1c patients). METHODS: Between 1987 and 1995 there were 643
      patients with DRE-Stage T1-T2 prostate cancer treated with external beam
      radiotherapy; 24 had T1a, 76 had T1b, 183 had T1c, 133 had T2a, 168 had T2b, and
      59 had T2c. Of these, 135 DRE-Stage T1c patients underwent ultrasound staging and
      122 underwent bilateral prostate biopsies. All had pretreatment prostate-specific
      antigen values (PSAs) available and no patient received adjuvant androgen
      ablation. The median pretreatment PSA was 9.1 ng/mL, median radiotherapy dose was
      66.0 Gy, and median follow-up was 41 months. Post-treatment failure was defined
      as disease recurrence and/or two elevations in PSA on consecutive follow-up
      visits. RESULTS: The 5-year freedom from failure rate for DRE-Stage T1c patients
      (71%) was not significantly different from that of DRE-Stage T1b (65%) or DRE
      Stage T2a (71%) patients. There was a trend (P = 0.1) toward a worse outcome for
      DRE-Stage T2b/T2c patients compared with DRE-Stage T1b/T1c/T2a patients. The
      distribution of DRE-Stage T1c patients by ultrasound staging was 29 with uT1c, 88
      with uT2, and 18 with uT3 findings. Twenty percent of patients had bilateral
      positive biopsy specimens. In univariate and multivariate analyses, the only
      correlates of patient outcome were pretreatment PSA (P < or = 0.002) and
      isocenter dose (P = 0.03). TRUS upstaging had no effect on freedom from failure;
      uT1c patients had about the same risk of relapse or a rising PSA as uT2 or uT3
      patients. Patients with bilateral positive prostate biopsy specimens had about
      the same prognosis as those with unilateral positive biopsy specimens.
      CONCLUSIONS: For patients with DRE-Stage T1c prostate cancer, the data indicate
      that ultrasound staging and bilateral biopsy positivity are not predictive of
      outcome for patients treated with external beam radiotherapy and treatment
      decisions should not be based on these parameters.

PMID- 9763088
TI  - Estimation of prostate cancer volume by multiple core biopsies before radical
      prostatectomy.
AB  - OBJECTIVES: To investigate whether tumor volume, an important prognostic factor
      in prostate cancer, could be estimated from the amount of cancer in multiple core
      biopsies. METHODS: In 80 men, transrectal ultrasound-guided biopsies were taken
      from focal lesions detected by ultrasound and 8 to 10 standardized positions,
      including sextant biopsies (apex, midmedial, base) and midlateral and transition
      zone biopsies. The cancer length in the biopsies was measured. After radical
      prostatectomy, the prostates were totally embedded, whole-mounted, and tumor
      volume was measured planimetrically. RESULTS: The tumor volume correlated
      significantly with the total cancer length of all biopsies (r = 0.56) and of the
      sextant biopsies (r = 0.39). It was found that midlateral and transition zone
      biopsies provided independent information when included in a multiple regression
      model with tumor volume as the dependent variable and the sextant biopsies as
      explanatory variables. All men (n = 6) with less than 3 mm cancer length in only
      one positive biopsy and a Gleason score less than 7 had a tumor volume less than
      1 mL. Nine of 10 men with less than 7 mm of cancer in one positive biopsy and
      Gleason score less than 7 had tumors smaller than 1 mL. Sextant biopsies did not
      reliably predict cancer volumes less than 1 mL. CONCLUSIONS: The cancer yield of
      8 to 10 biopsies correlated better with the volume of prostate cancer than
      sextant biopsies. This extended biopsy protocol could be used to predict cancers
      of less than 1 mL in volume.

PMID- 9763089
TI  - Repeat transrectal ultrasound-guided prostate biopsy: a strategy to improve the
      reliability of needle biopsy grading in patients with well-differentiated
      prostate cancer.
AB  - OBJECTIVES: Gleason grade from prostate needle biopsy (PNB) specimens is
      important in guiding therapeutic decision making in patients with localized
      prostate cancer. Recent data from our institution suggest a significant
      discordance between Gleason grading from PNB versus the actual pathologic grade
      at radical prostatectomy (RRP). Of most concern is that a substantial proportion
      of patients with Gleason score of 6 or less from PNB actually have Gleason score
      of 7 or more at RRP. Under classic measurement theory, one useful way to improve
      the reliability of an inherently unreliable test is to repeat it. We investigated
      this strategy in an effort to reduce undergrading errors. METHODS: The control
      group of patients (n = 51) from our neoadjuvant androgen deprivation protocol was
      used as the test (two-biopsy) group in this study. These patients underwent two
      separate PNBs before RRP. We used the highest Gleason score from the two biopsies
      in these patients and compared the error rates with a concurrent group of
      patients treated at our institution (n = 226) who had only one set (single-biopsy
      group) of prostate biopsies. All pathologic slides were reviewed at our
      institution. Any PNB grade of 6 or less that was scored as 7 or more on final
      pathology was considered significant. RESULTS: Mean age, prostate-specific
      antigen levels, and stage distribution were not significantly different between
      these two groups. In the single-biopsy group, 165 patients had PNB Gleason score
      of 6 or less. Of these patients, 63 (38%) had final pathologic grade of 7 or
      more. In the two-biopsy group, 37 patients had PNB Gleason score of 6 or less. Of
      these patients, only 7 (19%) had final pathologic grade of 7 or more (P = 0.04).
      CONCLUSIONS: Prostate rebiopsy minimizes the inherent unreliability of PNB
      derived grade and should be considered for patients in whom watchful waiting or
      nomogram-based therapy has been selected.

PMID- 9763090
TI  - Evaluation of staging lymphadenectomy in prostate cancer.
AB  - OBJECTIVES: To prospectively evaluate a clinical algorithm that predicts nodal
      status in patients with prostate cancer and to assess the impact on the outcome.
      METHODS: Between September 1988 and December 1994, 192 patients with organ
      confined prostate cancer and considered surgical candidates for radical perineal
      prostatectomy (RPP) were stratified using the algorithm: prostate-specific
      antigen (PSA) 20 ng/mL or less, Gleason score 7 or lower, and clinical Stage T2a
      or lower. Patients failing any of these criteria were placed in the high-risk
      group and underwent a pelvic lymphadenectomy. Patients who satisfied all the
      criteria were placed in the low-risk group and underwent RPP without evaluation
      of the pelvic lymph nodes. Another contemporaneous cohort of patients (n = 65)
      underwent pelvic lymphadenectomy and radical retropubic prostatectomy (RRP)
      without use of the algorithm and were used as a control group. Patients were
      monitored for at least 24 months. RESULTS: In the RPP group, 177 patients were
      considered low risk according to the algorithm and were not offered staging
      lymphadenectomy before surgery, whereas 15 patients were categorized as high risk
      for metastasis and underwent staging lymphadenectomy. In the RRP and
      lymphadenectomy group, 41 patients were considered at low risk and 24 at high
      risk of disease spread according to the algorithm. In the RPP group, low-risk
      patients (no lymphadenectomy) had a PSA recurrence rate (27%) similar to that of
      low-risk patients in the RRP group with negative lymph nodes (29%), P = 0.8.
      Similarly, high-risk patients with negative lymph nodes in both groups had a
      similar recurrence rate (53% for RPP and 50% for RRP). Univariate logistic
      regression analysis showed that PSA was the most significant predictor for
      disease recurrence (P = 0.0004) followed by preoperative Gleason scores (P =
      0.02) and clinical stages (P = 0.03). Multivariate stepwise analysis demonstrated
      that Gleason score and clinical stage did not add to the prediction of recurrence
      over PSA alone. CONCLUSIONS: Staging lymphadenectomy can be omitted in low-risk
      patients without deleterious effects on the outcome as measured by PSA
      recurrence.

PMID- 9763091
TI  - Bladder neck prop using vaginal wall island for intrinsic sphincteric deficiency
      in elderly patients: a new technique.
AB  - OBJECTIVES: A simple new technique, using a trapezoid island of vaginal wall, is
      described for elderly female patients undergoing transvaginal pelvic prolapse
      repair and suffering from stress urinary incontinence secondary to intrinsic
      sphincteric deficiency. METHODS: Fifteen elderly women underwent bladder neck
      prop in association with other pelvic prolapse surgery. The mean follow-up period
      was 20 months. RESULTS: Twelve of 14 patients (85.7%) were dry. One patient was
      lost to follow-up. CONCLUSIONS: Bladder neck prop provided urethral and bladder
      neck compression and support. The major advantage of this approach is avoiding
      extensive dissection and/or abdominal incision in elderly female patients.

PMID- 9763092
TI  - Patient perspective of long-term outcome of augmentation cystoplasty for
      neurogenic bladder.
AB  - OBJECTIVES: Although the urologic outcomes of augmentation cystoplasty for
      neurogenic bladder dysfunction are well known, additional information about the
      patient perspective is needed. The aim of this study was to assess patient
      perspective using a standardized questionnaire. METHODS: Fifty-nine patients, who
      had undergone augmentation enterocystoplasty as part of reconstruction mainly to
      correct hyperactive bladders and incontinence, were subjected to a questionnaire
      after a median of 76.1 postoperative months. The questionnaire addressed
      medications, catheterization, incontinence, bowel dysfunction, and satisfaction
      with urinary tract management. The urologic outcomes regarding upper and lower
      tract changes, complications, and reinterventions were documented as well.
      RESULTS: The patients experienced a significant increase in bladder capacity and
      decrease in pressure at capacity (P < 0.0001). Normal upper tracts remained
      normal and there was either improvement or stabilization of hydronephrosis.
      Twenty-four patients (40.6%) had one or more complications, with 21 requiring
      reinterventions. Twenty-five percent of patients required the reintervention
      within the first 25 months, and the median time to reintervention was almost 10
      years. Thirty-five patients took medications such as anticholinergics,
      antidiarrheals, or antibiotics. Fifty-six patients were treated with clean
      intermittent catheterization (CIC) at a mean interval of 4.6 hours. Seven
      patients had some difficulty with CIC. Thirty-nine patients (67%) were dry, and
      17 had mild and 3 severe incontinence. Eleven patients (18.6%) reported bowel
      dysfunction, although 7 had it preoperatively. Almost all patients were very
      satisfied with their urologic management. CONCLUSIONS: The high degree of patient
      satisfaction attests to the value of the procedure. The complication and
      reintervention rates underscore the importance of long-term follow-up.

PMID- 9763093
TI  - Stimulated pressure profile at rest: a noninvasive method for assessing urethral
      sphincter function.
AB  - OBJECTIVES: To validate a method for assessing urethral sphincter muscle function
      by recording rises in intraurethral pressure during repetitive pudendal nerve
      stimulations. METHODS: A supine urethral pressure profile at rest was performed
      on 12 stress-continent and 28 stress-incontinent patients during repetitive
      pudendal nerve stimulations applied near the ischial spine, and the intraurethral
      pressure increases were calculated for each third of the urethral functional
      length. RESULTS: No significant difference in intraurethral pressure increases
      was seen between continent and stress-incontinent women. On the various
      regression curves, the intraurethral pressure increases showed a significant
      correlation with maximal urethral closure pressure values at rest and at stress
      (r = 0.36 to 0.54) and with the patient's age (r = 0.46), but not with pudendal
      nerve conduction times to the urethral sphincter on either side (r = 0.14 and
      0.19). CONCLUSIONS: This method (1) measures intraurethral pressure increases
      that correlate well with the anatomic location of the urethral sphincter muscle,
      (2) shows there is no significant difference between them in continent and stress
      incontinent patients, except in patients with a low-pressure urethra, and (3)
      demonstrates that they correlate well with the maximal urethral closure pressure
      and the patient's age, but not with pudendal motor latencies to the urethral
      sphincter. This method gives us a mapping of the urethral sphincter activity,
      explaining why some patients with a low-pressure urethra have less urinary loss
      than others with the same urethral closure pressure.

PMID- 9763094
TI  - Clinical aspects of vasectomies performed in the United States in 1995.
AB  - OBJECTIVES: Currently, no surveillance system collects data on the numbers and
      characteristics of vasectomies performed annually in the United States. This
      study provides nationwide data on the numbers of vasectomies and the use of no
      scalpel vasectomy, various occlusion methods, fascial interposition, and
      protocols for analyzing semen after vasectomy. METHODS: A retrospective mail
      survey (with telephone follow-up) was conducted of 1800 urology, family practice,
      and general surgery practices drawn from the American Medical Association's
      Physician Master File and stratified by specialty and census region. Mail survey
      and telephone follow-up yielded an 88% response rate. RESULTS: In 1995,
      approximately 494,000 vasectomies are estimated to have been performed by 15,800
      physicians in the United States. Urologists performed 76% of all vasectomies, and
      nearly all (93%) urology practices performed vasectomies in 1995. Nearly one
      third (29%) of vasectomies in 1995 were no-scalpel vasectomies, and 37% of
      physicians performing no-scalpel vasectomies taught themselves the procedure. The
      most common occlusion method in 1995 (used for 38% of all vasectomies) was
      concurrent use of ligation and cautery. In 1995, slightly less than half (48%) of
      all physicians surveyed interposed the fascial sheath over one end of the vas
      when performing a vasectomy. Protocols for ensuring azoospermia varied: 56% of
      physicians required one postvasectomy semen specimen; 39% required two, and 5%,
      three or more. CONCLUSIONS: No-scalpel vasectomy, used by nearly one third of
      U.S. physicians, has become an accepted part of urologic care. Physicians'
      variations in occlusion methods, use of fascial interposition, and postvasectomy
      protocols underscore the need for large scale, controlled, and statistically
      valid studies to determine the efficacy of occlusion methods and fascial
      interposition, as well as whether azoospermia is the only determination of a
      successful vasectomy.

PMID- 9763095
TI  - Testicular sperm extraction for nonobstructive azoospermia: results of a
      multibiopsy approach with optimized tissue dispersion.
AB  - OBJECTIVES: Testicular sperm extraction (TESE) is an effective procedure to
      retrieve sperm from some men with nonobstructive azoospermia (NOA). To optimize
      treatment effectiveness, we have reviewed our experience with TESE for NOA to
      better understand technical factors needed for sperm retrieval and lead to an
      optimized approach to TESE. METHODS: Eighty-one men with confirmed NOA underwent
      attempted TESE using an open technique under optical magnification. Each testis
      sample was dispersed and examined in the operating room. Sequential biopsy
      attempts were made until sperm were visualized or until further biopsies were
      thought to jeopardize testicular blood flow. In 20 patients, standard biopsy and
      initial mechanical dispersion of the seminiferous tubules were compared with the
      passage of tissue through a 24-gauge angiocatheter after initial dispersion to
      quantitate spermatozoal yield. RESULTS: Overall, 47 (58%) of 81 patients who
      underwent TESE had direct intraoperative visualization of spermatozoa. The
      average number of biopsy attempts for all patients was 8.9 and for patients with
      sperm isolated 6.4 (P = 0.002). Passage of the testicular tissue suspension
      through a 24-gauge angiocatheter increased sperm retrieval in matched tissue
      specimens from 83,000 to 390,000 or 470% over that achieved with standard
      dispersion alone (P = 0.005). An initial, substantive tissue biopsy revealed
      sperm in only 23 (28%) of 81 patients. Using this approach with sequential
      biopsies under optical magnification, no patient had evidence of testis injury or
      devascularization. CONCLUSIONS: Because multiple TESE procedures can cause
      transient and permanent alterations in testicular function, it is imperative to
      perform TESE as safely and as efficiently as possible. We suggest that open TESE
      with optical magnification provides a safe method of retrieving sperm. A single
      biopsy for extraction is inadequate to detect spermatozoa for men with NOA. Use
      of the needle dispersion technique with passage of testicular tissue through an
      angiocatheter enhances detection of sperm and could potentially reduce the need
      for subsequent biopsies. An algorithm to minimize biopsies and allow sperm
      retrieval is presented.

PMID- 9763096
TI  - Percutaneous nephrolithotomy in infants and preschool age children: experience
      with a new technique.
AB  - OBJECTIVES: To develop a less invasive method for performing percutaneous
      nephrolithotomy (PCNL) with the intent of decreasing the morbidity of the
      procedure in young children. METHODS: A novel percutaneous renal access technique
      ("mini-perc") was developed using an 11F peel-away vascular access sheath. Tract
      dilation and insertion of the sheath into the collecting system was performed
      with a single pass over an access wire. PCNL was performed using pediatric
      instruments and electrohydraulic lithotripsy. Sheath design improvements were
      implemented that make it specific for pediatric PCNL. RESULTS: Eleven procedures
      have been performed with the 11F sheath. Patient age ranged from 2 to 6 years
      (mean 3.4) and weight from 5 to 24 kg (mean 12.5). The average stone burden was
      1.2 cm2. Mean procedure time, estimated blood loss, and length of hospitalization
      were 203 minutes, 25 mL, and 6 days, respectively. Six (85%) of 7 patients are
      currently stone free with an average follow-up of 12 weeks. No patient required
      transfusion, developed urosepsis, or had a procedure-related complication. One
      procedure was performed in an outpatient setting with no postoperative
      nephrostomy tube. CONCLUSIONS: The 11F "mini-perc" technique was successful in
      rendering 85% of patients stone free with minimal morbidity. Its advantages over
      obtaining access with standard 24 to 34F access sheaths include a smaller skin
      incision, single-step dilation and sheath placement, good working access for
      pediatric instruments, variable length, and lower cost. In addition, the
      hypothesized decrease in renal and body wall trauma may result in less pain,
      reduced severity or risk of complications, and shorter hospital stays including
      the possibility of performing "tubeless" outpatient PCNLs. Further study is
      needed to confirm these possibilities.

PMID- 9763098
TI  - 20th biannual meeting of the Society for Fetal Urology.

PMID- 9763097
TI  - Cecoappendicovesicostomy: conduit-lengthening technique for use in continent
      urinary reconstruction.
AB  - OBJECTIVES: To describe a conduit-lengthening technique for use in continent
      cutaneous appendicovesicostomy (Mitrofanoff procedure). METHODS: Fifteen
      consecutive patients (4 male, 11 female) with a mean age of 14.2 years underwent
      tubularized cecal augmentation as a means to lengthen the catheterizable conduit
      while performing continent cutaneous appendicovesicostomy. RESULTS: All patients
      successfully underwent appendiceal lengthening by tubularizing the cecum, thus
      creating a continent cutaneous cecoappendicovesicostomy. With a mean follow-up of
      18.7 months, all patients have a working catheterizable conduit. One case of
      stomal stenosis occurred, producing a 6.7% conduit-related complication rate.
      CONCLUSIONS: Cecoappendicovesicostomy is a safe and useful means of conduit
      lengthening for patients undergoing continent cutaneous appendicovesicostomy
      (Mitrofanoff procedure).

PMID- 9763099
TI  - Images in clinical urology. Suture nidus as a cause for renal nephrolithiasis.

PMID- 9763100
TI  - Images in clinical urology. Venous cavernous hemangioma of the testis.

PMID- 9763102
TI  - Radical prostatectomy in patients with indwelling inflatable penile prosthesis.
AB  - Patients with impotence who have undergone placement of an inflatable penile
      prosthesis (IPP) and then subsequently are diagnosed with carcinoma of the
      prostate (CaP) present a surgical dilemma. We performed radical retropubic
      prostatectomy on 3 patients with clinically localized CaP and an indwelling IPP.
      At laparotomy all 3 patients had the IPP reservoir relocated to facilitate
      dissection. In each case the reservoir was relocated to the left hypogastrium
      within the extraperitoneal space without disrupting the vacuum tubing system.
      There were no complications related to IPP, no IPP was injured, and each IPP was
      reactivated successfully 6 weeks after surgery.

PMID- 9763101
TI  - Bilateral adrenal cortical adenomas in primary hyperaldosteronism.
AB  - Bilateral adrenal cortical adenomas in the presence of primary hyperaldosteronism
      is an extremely rare condition. We present a case of primary hyperaldosteronism
      in which a unilateral hypersecreting aldosterone-producing adenoma coexisted with
      a large, contralateral adrenal mass ultimately found to be consistent with
      cortical adenoma. Management consisted of total adrenalectomy and enucleation of
      adenoma from the opposite adrenal. The patient is normotensive 3 years after
      surgery. Enucleation as a successful approach to hyperfunctioning cortical
      adenomas is proposed.

PMID- 9763103
TI  - Repair of penile rupture through a high-scrotal midline raphe incision.
AB  - We report a case of penile rupture after a self-inflicted injury, which was
      repaired through a 4-cm midline raphe incision in the high-scrotal position. A
      single injury to the right lateral corpora cavernosum was identified and
      repaired. This incision allows for exposure of all three corporal bodies and
      results in excellent cosmesis. Creating artificial tumescence with intracorporal
      saline injection can be useful in identifying small or multiple sites of corporal
      injury. This may obviate the need for performing a routine degloving procedure,
      which results in unnecessary dissection, increased edema, and potential visible
      scarring of the penile skin.

PMID- 9763105
TI  - Androgen induction of DNA synthesis in the rat penis.
AB  - OBJECTIVES: The androgen sensitivity of the mammalian penis has long been
      appreciated. However, the precise biochemical and structural sequelae of
      alterations in testosterone, and the mechanisms thereof, remain to be elucidated.
      Recently, the androgen dependence of rat penile erectile tissue was further
      clarified at our institution, where the induction of apoptosis was demonstrated
      in response to castration. In continuity, we report the results of a follow-up
      study of the regenerative capacity of the regressed, castrated rat penile
      erectile tissue when testosterone is replenished. METHODS: Three groups of rats
      were used: normal control rats, castrated without testosterone replenishment, and
      castrated with subsequent testosterone replenishment. In the third group,
      castrated rats were given testosterone and killed at 24-hour intervals over 4
      days. Specimens of the penis, small bowel, and prostate were obtained from all
      animal groups. Immunohistochemical identification of intraperitoneally
      administered 5-bromo-2'-deoxyuridine, a thymidine analogue, was performed to
      detect new DNA synthesis. The incorporation of this molecule into high molecular
      weight nuclear DNA served as a measure of DNA synthesis and, hence, cellular
      proliferation. RESULTS: Testosterone-replenished castrated rat penile stromal
      cells, both cavernosal and spongiosal, showed more enhanced proliferative
      activity than those of both castrated unreplenished and uncastrated control rats.
      Trichrome staining permitted the differentiation of responsive cell subsets.
      Various cell types were found to respond to replenished testosterone, including
      myocytes, fibrocytes, endothelial cells, and Schwann cells. Pronounced DNA
      synthesis occurred as early as 48 hours after the replenishment of testosterone.
      For purposes of technique validation, sections of small bowel were examined, in
      which glandular crypt cells would be expected to show rapid turnover. The nuclei
      of these bowel sections stained in all animal groups throughout the experiment,
      thus validating the staining technique. The technique of castration and
      testosterone replenishment was validated by confirming the known response of rat
      ventral prostate to androgen withdrawal and replenishment. CONCLUSIONS: Our
      findings provide evidence that testosterone induces cellular proliferation and
      new DNA synthesis in the penile erectile tissue of castrated rats. This response
      to testosterone is not limited to one cell type, but rather is multicellular.

PMID- 9763106
TI  - History of direct vision internal urethrotomy.
AB  - Throughout medical history, the treatment of urethral strictures ranged from
      catheterization, the insertion of bougies, and the application of caustics to
      different methods of dilation, blind internal urethrotomy, and open surgery. The
      rise of endoscopy in the 19th century added the possibility of direct vision
      internal urethrotomy to this therapeutic spectrum. The development of this
      endourologic method is recapitulated from the first report in 1865 to the gold
      standard of cold knife urethrotomy in 1971 and later modifications (eg, advanced
      laser techniques).

PMID- 9763104
TI  - Hematuria and death secondary to aortoureteric fistula.
AB  - Ureteroarterial fistulae are extremely rare after previous vascular surgery.
      Eight cases have been described in the English literature. This is the first
      example of a vascular communication between the aorta and the ureter. All
      previous cases were ureteroiliac fistulae. Known hydronephrosis in the presence
      of prior vascular grafting and heavy hematuria should alert the clinician to the
      possibility of a ureteroarterial fistula.

PMID- 9763107
TI  - Management of possible sexual, injecting-drug-use, or other nonoccupational
      exposure to HIV, including considerations related to antiretroviral therapy.
      Public Health Service statement. Centers for Disease Control and Prevention.
AB  - The most effective methods for preventing human immunodeficiency virus (HIV)
      infection are those that protect against exposure to HIV. Preventive behaviors
      include sexual abstinence, sex only with an uninfected partner, consistent and
      correct condom use, abstinence from injecting-drug use, and consistent use of
      sterile equipment by those unable to cease injecting-drug use. Some healthcare
      providers have proposed offering antiretroviral drugs to persons with
      unanticipated sexual or injecting-drug-use HIV exposure to prevent transmission.
      However, because no data exist regarding the efficacy of this therapy for persons
      with nonoccupational HIV exposure, it should be considered an unproven clinical
      intervention. Health-care providers and their patients may opt to consider using
      antiretroviral drugs after nonoccupational HIV exposures that carry a high risk
      for infection, but only after careful consideration of the potential risks and
      benefits and with a full awareness of the gaps in current knowledge. To address
      concerns related to providing antiretroviral agents to persons after
      nonoccupational HIV exposure, CDC convened a meeting in July 1997 of scientists,
      public health experts, clinicians, members of professional associations,
      representatives from industry, ethicists, and members of affected communities.
      This report reviews the topics raised at the meeting, provides background
      information on patient management options, and presents considerations for
      antiretroviral therapy.

PMID- 9763108
TI  - Ex vivo expansion of immature 4-hydroperoxycyclophosphamide-resistant progenitor
      cells from G-CSF-mobilized peripheral blood.
AB  - The application of ex vivo expansion to cell products pharmacologically purged in
      vitro may provide sufficient numbers of cells for rapid engraftment in a product
      with reduced tumor burden. To pursue this possibility we evaluated the effect of
      4-hydroperoxycyclophosphamide (4-HC) treatment on granulocyte colony-stimulating
      factor-mobilized peripheral blood stem cells (G-PBSC) and their subsequent
      expansion potential. A small number of G-PBSC CD34+ cells are resistant to 4-HC
      and are phenotypically and functionally immature. 4-HC-resistant G-PBSC cells are
      CD34+ bright, CD38+/-, DR(lo), CD13(lo), CD33-, CD71-, and rhodamine dull. In six
      experiments, treating G-PBSC with 60 microg/mL of 4-HC at 37 degrees C for 30
      minutes reduced the number of colony-forming units (CFUs) per 5000 CD34+ cells by
      96.3% (from 1333 +/- 137 to 46.5 +/- 11). This purging also reduced the frequency
      of 5-week long-term culture initiating cells (LTC-ICs) from 1/39 (range 1/27 to
      1/62) to <1/1680 (range 1/1180 to 1/2420). Ex vivo expansion cultures were used
      to compare the proliferative potential of treated and untreated CD34+ cells.
      These cells were cultured with either the HS-5 stromal cell line serum-deprived
      conditioned media supplemented with 10 ng/mL kit ligand (HS-5CM/KL) or a
      recombinant growth factor mix (GFmix) containing 10 ng/mL each of interleukin
      (IL)-1, IL-3, IL-6, KL, granulocyte colony-stimulating factor, granulocyte
      macrophage colony-stimulating factor, and 3 U/mL of erythropoietin. Culturing
      untreated CD34+ G-PBSC with 10% HS-5CM/KL increased total nucleated cells by 460
      fold after 15 days. Progenitors, which were measured as CFUs, also increased by
      47-fold over the same period. More significantly, culturing the 4-HC-treated
      CD34+ cells with HS-5/KL increased CFUs 98-fold and the nucleated cells increased
      4573-fold. The absolute number of CFUs present after expansion of the 4-HC
      resistant cells with HS-5CM/KL was threefold higher than that detected before
      purging and significantly higher than that obtained with GFmix. These data
      indicate that G-PBSC contain a very immature pool of cells not detectable using
      the 5-week LTC-IC assay, but have extremely high proliferative potential.
      Additionally, pharmacological purging of G-PBSC greatly reduces mature cells
      while retaining an immature population. Also significant is the finding that
      supernatant from the HS-5 bone marrow stromal cell line plus KL can fully
      regenerate progenitors from the 4-HC-resistant CD34+ G-PBSC.

PMID- 9763110
TI  - CD20 is a molecular target for scFvFc:zeta receptor redirected T cells:
      implications for cellular immunotherapy of CD20+ malignancy.
AB  - The CD20 molecule was evaluated as a B-cell lymphoma target epitope for T cells
      expressing a CD20-specific single-chain FvFc-zeta (scFvFc:zeta) chimeric
      receptor. A cDNA construct consisting of a murine kappa leader sequence, CD20
      specific scFv, human immunoglobulin (Ig) G1 hinge-C(H)2-C(H)3, the human CD4
      transmembrane, and the intracellular signaling domain of the human CD3 complex's
      zeta chain was synthesized by polymerase chain reaction splice-overlap extension.
      The human CD4+ Jurkat cell line was electroporated with the CD20-specific
      scFvFc:zeta construct cloned into the mammalian expression vector pcDNAneo.
      Western blot analysis of transfectant whole cell lysate with an anti-zeta
      antibody demonstrated the expression of both endogenous zeta and the chimeric
      receptor protein, with a mobility consistent with the expected molecular weight
      of 66 kD under reducing conditions; nonreduced lysate revealed a chimeric
      receptor complex of approximately 132 kD. The scFvFc:zeta receptor was present on
      the cell surface as detected by flow cytometry of T-cell transfectants stained
      with an anti-mouse Fab-specific antibody and anti-human Fc gamma-specific
      monoclonal antibody. Coculture of Jurkat transfectants with CD20+ lymphoma cells
      resulted in the accumulation of interleukin (IL)-2 in culture supernatants as
      detected by ELISA. IL-2 production was triggered by the specific interaction
      between the CD20 molecule and the scFvFc:zeta as IL-2 was not detected in
      cultures with mock transfected Jurkat cells or CD20- stimulator cells.
      Furthermore, IL-2 production was inhibited by the addition of a soluble anti-CD20
      monoclonal antibody to cocultured Jurkat transfectants and CD20+ stimulator
      cells. The capacity of CD20 to trigger the lytic machinery of scFvFc:zeta
      expressing cytotoxic T lymphocytes (CTLs) was assessed using the murine allo
      specific CD8+ CTL clone 2c. CD20-specific redirected cytolytic activity against
      human lymphoma targets was observed with 2c transfectants in a 4-hour chromium
      release assay. These results demonstrate that CD20 can serve as a target epitope
      for scFvFc:zeta receptor-expressing T cells.

PMID- 9763109
TI  - c-Kit and CD38 are expressed by long-term reconstituting hematopoietic cells
      present in the murine yolk sac.
AB  - Murine fetal liver (FL) and adult bone marrow (BM) hematopoietic stem cells
      (HSCs) are characterized by cell surface expression of CD38 and c-kit. Because
      murine yolk sac (YS) HSC activity precedes the initiation of FL hematopoiesis, we
      investigated whether YS-derived HSCs also expressed c-kit and CD38. c-Kit+ CD38+
      lineage- cells derived from day 9 YS as well as adult BM were found to be
      enriched in high proliferative potential colony-forming cells. c-Kit+ CD38+
      lineage- YS or adult BM cells were capable of long-term reconstitution (>6
      months) of busulfan-conditioned newborn or lethally irradiated adult mice,
      respectively. In contrast, c-kit+ CD38- lineage- populations from both tissues
      were enriched in lineage-committed progenitors and had no long-term HSC activity.
      We concluded that c-kit and CD38 are cell surface markers of HSCs expressed
      throughout murine ontogeny.

PMID- 9763111
TI  - Effect of CD34+ peripheral blood progenitor cell dose on hematopoietic recovery.
AB  - The CD34+ cell surface antigen is expressed on progenitor cells required for
      blood stem cell transplantation. The number of cells expressing CD34+ can be used
      to assess the peripheral blood progenitor cell (PBPC) graft quality and predict
      hematopoietic recovery after engraftment. Because there is considerable
      variability among centers in the determination of CD34+ cell counts,
      standardizing flow cytometry methodology is essential. It is necessary to define
      a minimum safety threshold CD34+ cell dose for hematopoietic cell
      transplantation. This minimum dose would define a cell number in the graft, below
      which a proportion of patients would be expected to have delayed hematopoietic
      recovery or failure to engraft. We reviewed data from numerous studies. Although
      1-2 x 10(6) CD34+ cells/kg can be considered an adequate graft, available data
      suggested that doses >5 x 10(6) CD34+ cells/kg were associated with more rapid
      engraftment and a lower probability of graft failure. The risk of delayed
      recovery was inversely related to CD34+ cell dose. Delayed recovery may result in
      greater transfusion requirements, longer hospitalization, increased antibiotic
      use and growth factor support, and higher health care costs. The extent of prior
      chemotherapy and radiation treatment are major risk factors for poor PBPC
      collection. To achieve an optimal CD34+ cell yield, PBPC collection should be
      initiated early during therapy. PBPC collection should be coordinated with the
      anticipated number of chemotherapy cycles, duration of chemotherapy, interval
      between chemotherapy and apheresis, need for radiotherapy, and exposure to the
      more progenitor cell-toxic drugs such as carmustine or busulfan.

PMID- 9763112
TI  - Understanding molecular biology.
AB  - Vascular disease is more commonly being studied at a molecular level. The
      knowledge derived is being applied to our understanding of clinical vascular
      disease processes and reconstruction outcome. Furthermore, applications are
      increasingly found for diagnosis and even intervention. The fundamental concepts
      and techniques involved in molecular biology are presented.

PMID- 9763113
TI  - The pathophysiology of atherosclerosis.
AB  - Complications resulting from advanced atherosclerosis are the most common
      indication for vascular reconstructive surgery. Atherosclerosis is a systemic
      disease affecting the entire arterial tree, but lesions involving the coronary,
      extracranial cerebral, and lower extremity circulations have the most clinical
      significance for surgeons. The pathogenesis of atherosclerosis involves a complex
      series of events, similar to a chronic inflammatory process, with the formation
      of atherosclerotic plaque as the end result. Injury to the endothelial cell of
      the artery, resulting in endothelial cell dysfunction, is the first step in the
      process. Activated endothelial cells attract leukocytes and vascular smooth
      muscle cells (VSMC), which accumulate and proliferate in the arterial wall. These
      cellular components produce an excessive amount of connective tissue matrix. The
      ultimate end point is the formation of a mature fibrous plaque. Symptoms occur
      when advanced lesions are complicated by plaque rupture, hemorrhage into the
      plaque, emboli, or thrombosis. A thorough understanding of the pathogenesis of
      atherosclerosis is essential for the development of strategies for the prevention
      of the disease, and for the development of new and effective treatments.

PMID- 9763115
TI  - Peptide growth factors and signal transduction.
AB  - Cell differentiation and proliferation are influenced by peptide growth factors.
      These peptide molecules are important in maintaining the normal development and
      growth of animal cells; in addition, they have been found to play a major role in
      disease states. The role of growth factors in the development of arteriosclerosis
      and intimal hyperplasia is of great interest to us as physicians taking care of
      patients with peripheral vascular disease. Factors such as platelet-derived
      growth factor (PDGF), fibroblast growth factor (FGF), insulin, insulin-like
      growth factor-I (IGF-I), and transforming growth factors alpha and beta (TGF
      alpha and beta) have been found to play important roles in controlling the
      progression of cells in the cell cycle. Furthermore, various growth factors have
      been found to influence the motility of cells, particularly vascular smooth
      muscle cells (VSMCs).

PMID- 9763114
TI  - Myointimal hyperplasia: basic science and clinical considerations.
AB  - The mechanical injury caused by a bypass procedure or angioplasty of the coronary
      or peripheral arteries can initiate and maintain the process of myointimal
      hyperplasia. Myointimal hyperplasia is of great clinical importance. The
      development of the hyperplastic lesion at the outflow anastomosis of a prosthetic
      bypass or in autogenous saphenous vein bypass placed in the arterial system is
      responsible for most bypass failures. It is also the primary cause of restenosis
      after coronary angioplasty. Myointimal hyperplasia is a complex pathological
      process of the vascular system characterized by an abnormal proliferation of
      smooth muscle cells of the vascular wall. Proliferating smooth muscle cells
      migrate to the subendothelial area and form the hyperplastic lesion, which causes
      stenosis and obstruction of the vascular lumen. The pathogenesis of myointimal
      hyperplasia remains under investigation. However, it has been established that
      both mechanical and chemical factors may induce this process. Arterial injury is
      believed to stimulate the production of growth factors, such as platelet-derived
      growth factor (PDGF), which have been shown to stimulate the proliferation of
      arterial smooth muscle cells and the formation of the hyperplastic lesion in the
      vascular system. These growth factors and cytokines have been found to be
      secreted by a variety of cells, including endothelial cells, macrophages,
      platelets, and arterial smooth muscle cells. Blocking the effects of growth
      factors such as PDGF or fibroblast growth factor (FGF), by the administration of
      their antibodies, has been shown to limit the development of the hyperplastic
      lesion. In this article, we begin with the basic physiology of myointimal
      hyperplasia. We then address possible therapeutic considerations for the future.

PMID- 9763116
TI  - Risk factors and their role in the diseases of the arterial wall.
AB  - The leading cause of death and disability in developed nations is
      atherosclerosis. Multiple risk factors, including hyperlipidemia, cigarette
      smoking, diabetes mellitus, and hypertension, predispose to the development of
      atherosclerosis. The mechanisms by which these risk factors exacerbate
      atherosclerosis involve the potentiation of endothelial and smooth muscle cell
      dysfunction as well as disturbances in coagulation. These mechanisms are
      discussed in detail in this chapter. Understanding the pathophysiology of how
      risk factors accelerate the progression of atherosclerosis will aid the clinician
      in attempts to treat the atherosclerotic patient.

PMID- 9763117
TI  - Arterial hemodynamics and wall mechanics.
AB  - Arterial hemodynamics and wall mechanics are important considerations for the
      vascular clinician for a number of reasons. Hemodynamics and wall mechanics both
      have been shown to be affecters of disease formation. It is important for the
      practicing vascular surgeon to know how disease affects both blood flow and wall
      mechanics and to understand the consequence of hemodynamics on arterial
      reconstructions. In this article, we summarize the basic concepts of arterial
      hemodynamics and wall mechanics as they relate to the development of arterial
      pathology. A few practical mathematical relationships and examples are provided
      for both illustration and utilization. We also discuss the use of computer models
      for the estimation of wall stresses in individual abdominal aortic aneurysms.

PMID- 9763118
TI  - Vasomotor tone and the role of nitric oxide.
AB  - Vasomotor tone is the end result of a complex set of interactions that control
      relaxation and contraction of blood vessels. The critical role of nitric oxide
      (NO) in modulating vasomotor tone has become increasingly apparent over the last
      15 years. A phenomenal amount of resources have been invested in the study of
      this simple molecule, and the volume of scientific literature that has resulted
      is astounding. In this review, we discuss the pertinent physiology and
      biochemistry of NO as it relates to the control of vasomotor tone. Methods of
      measuring NO in basic science and clinical settings are outlined, and the
      derangements of endothelial NO production and release (endothelial dysfunction)
      in pathophysiologic and disease states are discussed. Finally, potential
      therapies aimed at preserving endothelial function and augmenting NO production
      also are reviewed.

PMID- 9763119
TI  - The formation of aneurysms.
AB  - Arterial aneurysms account for a significant proportion of the various diseases
      treated by the vascular surgeon. Refinements of surgical technique have reduced
      the morbidity and mortality, yet, we have no effective medical therapy to prevent
      the growth of small aneurysms. Although the pathogenesis of aneurysmal disease
      has received attention, the complex nature of the process has not been fully
      elucidated. The emergence of new and refined techniques in the fields of
      immunology, biochemistry, cell biology, and genetics has advanced the
      understanding of the dynamic interactions within a diseased vessel. Although past
      work was descriptive, investigators are now studying the role of the local
      inflammatory infiltrates and the destructive proteolytic enzymes they produce and
      regulate. The clinical observations we make regarding the familial tendency of
      abdominal aortic aneurysms (AAA) underscores the importance of research directed
      at identifying an aneurysm-related gene. As new pieces are added to the puzzle
      and the picture of AAA pathogenesis becomes more clear, we can expect the
      development of new therapeutic measures directed at controlling the critical
      matrix changes, and thus the growth of small AAA, as well as screening methods
      searching for AAA-associated genes.

PMID- 9763120
TI  - Microvascular pathophysiology of skeletal muscle ischemia-reperfusion.
AB  - Ischemia-reperfusion injury is a continuing challenge to vascular surgeons.
      Microvascular factors and mechanisms underlying edema and compartment syndrome
      provide a useful end point for analysis and planning of therapy. We review the
      pivotal role of endothelium-leukocyte interactions and of cytokines in the
      genesis of postischemic damage in muscle. Clinical considerations and future
      directions based on research and practice are presented.

PMID- 9763121
TI  - Gene therapy.
AB  - Gene therapy for vascular disease is in the beginning stages. Each year
      investigators are increasing our understanding of the molecular and cellular
      biology of vascular disease and its complications. Our genes exert exquisite
      control over the expressed molecular pattern that results in biological function
      and pathology. Gene transfer techniques can be used to affect the pattern of gene
      expression. Gene therapy is a powerful tool that will allow specific manipulation
      of the genetic cascade that determines biological function. Gene transfer
      techniques should help to define the molecular mechanisms involved in vascular
      pathology, such as atherosclerosis and its complications. Currently, gene therapy
      has only reached clinical trials, but this new technology will likely play a
      major role in our treatment of vascular problems in the future. An understanding
      of the significance of this new technology is important for both health care
      providers and patients.

PMID- 9763122
TI  - Improved detection of capripoxvirus in biopsy samples by PCR.
AB  - A simple test based on the polymerase chain reaction (PCR) was used to detect
      capripoxvirus DNA in tissue culture supernatants and biopsy samples. The identity
      of the PCR products was confirmed by restriction enzyme analysis. The test has
      greater sensitivity and good specificity compared to an antigen trapping enzyme
      linked immunosorbent assay which uses a detector antibody raised against a
      recombinant capripoxvirus-specific antigen. The reagents for the PCR-based test
      are all available commercially and the test provides a valuable addition to the
      current methods of virus detection.

PMID- 9763123
TI  - Growth characteristics of fowl adenovirus type 8 in a chicken hepatoma cell line.
AB  - Fowl adenoviruses, many of which appear to be non-pathogenic, are ubiquitous in
      birds. In addition, the genome of these viruses is large, making them ideal
      candidates for construction as vectors for foreign genes. Current methods to
      cultivate fowl adenoviruses use primary cell cultures derived from embryonated
      chicken eggs. In order to provide a more suitable culture method, the growth of
      fowl adenovirus type 8 (FAdV-8) was investigated in CH-SAH, a continuous hepatoma
      cell line. A one step growth curve demonstrated release of extracellular virus
      beginning by 18 h p.i. and with a final yield about 100 fold higher than that in
      chicken embryo liver cells. Viral DNA synthesis was first detected 8 h prior to
      this. The CH-SAH cell line supported the production of progeny viruses similar to
      the wild-type virus after being transfected with purified FAdV-8 DNA. This study
      demonstrated that the continuous hepatoma cell line is an appropriate in vitro
      host for FAdV-8.

PMID- 9763124
TI  - PCR ELISA for the quantitative detection of Epstein-Barr virus genome.
AB  - A highly sensitive and nonradioactive microplate hybridization assay for the
      detection of Epstein-Barr virus (EBV)-specific polymerase chain reaction (PCR)
      product was developed. The PCR product is labelled by adding digoxigenin-dUTP
      directly to the reaction mixture and, after denaturation, is captured by a
      microtitre plate coated with an extravidin-linked biotinylated probe. Captured
      products are reacted with a peroxidase-conjugated anti-digoxigenin antibody and
      detected using tetramethylbenzidine. The assay detected less than ten EBV genomes
      in a background EBV-negative DNA of 0.75 microg and, when tested on clinical
      samples, it was able to define the viral load in throat washings of patients with
      acute infectious mononucleosis, immunosuppressed patients with HIV infection, and
      rare normal individuals who shed the virus in the oropharynx.

PMID- 9763125
TI  - Colourimetric PCR-based detection of monodon baculovirus in whole Penaeus monodon
      postlarvae.
AB  - The development of a nested polymerase chain reaction (PCR) assay is described to
      detect low concentrations of monodon baculovirus (MBV) DNA from total Penaeus
      monodon postlarval DNA. A modified DNA extraction procedure was also developed to
      circumvent problems associated with co-purification of PCR inhibitors in total
      DNA extracted from whole postlarvae. This method involved mechanical disruption
      of frozen prawn material immediately followed by phenol extraction at high
      temperature. An assessment of the sensitivity of the assay demonstrated detection
      down to eight viral genome equivalents. The PCR was shown to be specific for MBV
      DNA by not amplifying prawn DNA or DNA preparations of Baculovirus penaei (BP),
      white spot baculovirus (WSBV), bennettae baculovirus and insect Autographica
      californica nuclear polyhedrosis virus (NPV). A colourimetric method of PCR
      product detection was used to simplify final analysis.

PMID- 9763126
TI  - Development of a rapid and sensitive quantitative assay for rotavirus based on
      flow cytometry.
AB  - A very sensitive and accurate flow cytometry (FC) based method have developed to
      quantitate rotavirus infection in MA104 cells. Confluent cell monolayers were
      infected with serial dilutions of rotavirus SA11. After infection, the cells were
      recovered with the aid of trypsin and then reacted with monoclonal antibody M60
      (specific for the rotavirus outer capsid protein, VP7), followed by a second
      antibody (anti-mouse IgG-FITC). A FACScan FC was used to estimate the number of
      infected cells, as well as the level of infection. Viral infection was optimised
      by varying the concentration of trypsin used in the maintenance medium. The FC
      method enables many cells to be screened quickly for infectivity, and can detect
      low levels of virus. This method can be adapted to monitor the presence of other
      viruses in clinical and environmental samples without the need for prolonged
      periods of adaptation to growth in tissue culture.

PMID- 9763127
TI  - Recombinant Jembrana disease virus proteins as antigens for the detection of
      antibody to bovine lentiviruses.
AB  - Jembrana disease virus (JDV) is a recently identified bovine lentivirus causing
      an acute severe disease syndrome in banteng cattle (Bos javanicus) and a milder
      disease syndrome in Bos taurus cattle in Indonesia. The virus is closely related
      genetically to the previously identified bovine lentivirus, bovine
      immunodeficiency virus (BIV). Recombinant clones were produced which contained
      the capsid (CA) and transmembrane (TM) subunits of the respective gag and env
      open reading frames of JDV. The proteins were expressed as fusions to the
      glutathione-s-transferase (GST) enzyme in Escherichia coli and purification was
      achieved using affinity chromatography via immobilized reduced glutathione. The
      soluble recombinant CA and TM antigens of JDV were reacted in western immunoblots
      with both serum antibodies from JDV-infected Bos javanicus cattle and Bos taurus
      cattle immunized with BIV. The recombinant CA protein of JDV reacted equally well
      with both the JDV and BIV antisera. The recombinant TM protein of JDV also
      reacted with antibody from the JDV infected cattle and with the BIV antisera. The
      results indicated conservation of immunogenic epitopes of the CA and TM proteins
      of the two viruses. The production of the recombinant proteins should enable the
      development of rapid and sensitive serological tests for JDV and BIV, and tools
      for further study of the immune response to JDV and the differential epidemiology
      of JDV infections in cattle.

PMID- 9763128
TI  - Comparative detection of classical swine fever virus in striated muscle from
      experimentally infected pigs by reverse transcription polymerase chain reaction,
      cell culture isolation and immunohistochemistry.
AB  - Classical swine fever (CSF) is a highly contagious viral disease, which can be
      transmitted by CSFV-contaminated swill. In 1993, four CSF outbreaks in
      Switzerland were caused presumably by feeding pigs with improperly heated swill.
      The aim of the investigations was to find a suitable method for CSFV detection in
      striated muscle samples of infected pigs in order to allow routine testing of
      meat for virus contamination. The sensitivity of virus detection in striated
      muscle was compared with the detection in target organs. Using reverse
      transcription polymerase chain reaction (RT-PCR), cell culture isolation and
      immunohistochemistry on samples from 14 experimentally infected pigs, CSFV was
      detected in target organs of ten, and in striated muscle of six pigs,
      respectively. Overall, only 58% of muscle samples from CSFV-positive animals were
      positive by RT-PCR and 40% by virus isolation in cell culture, whereas the virus
      was detected in target organs of these pigs. Virus detection from striated muscle
      was primarily successful in severely diseased animals infected with highly
      virulent CSFV strains. It is concluded that striated muscle is not suitable for
      sensitive CSFV detection, and additional organs have to be examined for reliable
      diagnosis.

PMID- 9763129
TI  - Comparison of RNA hybridization, hemagglutination assay, titration of infectious
      virus and immunofluorescence as methods for monitoring influenza virus
      replication in vitro.
AB  - Rapid and sensitive methods for the monitoring of influenza virus replication in
      vitro are needed to address several research questions. Four methods based on
      different principles were compared: the hemagglutination (HA) assay, the
      measurement of virus infectivity titers in culture supernatants, the enumeration
      of infected cells by immunofluorescence and RNA hybridization techniques using
      digoxigenin (DIG) labeled RNA probes. To this end, MDCK cells were infected at
      different multiplicities of infection (moi) with a recent influenza A virus
      (A/Netherlands/18/94 H3N2) and the kinetics of virus replication were monitored
      with these four assays. At high moi, virus released into the culture supernatant
      of infected cells was detected by the HA assay 12 h post infection, whereas at
      lower moi (< or = 0.01) the first HA activity was not detected before 24 h post
      infection. The measurement of infectious viruses in the culture supernatant
      proved to be more sensitive, since 4-12 h post infection newly produced virus was
      detected depending on the moi used. This finding was in agreement with results
      obtained by the immunofluorescence assay using an antibody preparation specific
      for the nucleoprotein: single infected cells could be detected as early as 4 h
      post infection. At this time point, positive signals were also obtained when
      mRNA/cRNA specific hybridization was carried out for the NP gene segment, but not
      for viral NP RNA or RNA specific for the hemagglutinin, which were only detected
      at later time points after infection. Thus, besides direct measurement of
      infectious virus and immunofluorescence, RNA hybridization proved to be a
      sensitive assay for monitoring influenza virus replication in vitro.

PMID- 9763130
TI  - The GPRIME package: computer programs for identifying the best regions of aligned
      genes to target in nucleic acid hybridisation-based diagnostic tests, and their
      use with plant viruses.
AB  - The GPRIME (Group PRIMEr design) programs examine aligned sets of gene sequences
      to discover homologous regions to be targeted in diagnostic tests. The core
      program moves a 'window' over the aligned sequences and calculates, at each
      window position, a 'redundancy value', namely the number of sequences that would
      represent all permutations of the variable sequence positions within that window.
      Regions with minimal redundancy values may then be targeted in diagnostic tests
      based on oligonucleotide hybridisation. The likely specificity of tests targeting
      such regions can be assessed by searching the international databases with those
      regions using FASTA. The GPRIME programs, which include programs for designing
      primers to distinguish between two sub-sets of a group of aligned sequences, can
      be obtained from http://life.anu.edu.au/software.html. We have used GPRIME to
      design redundant primers for RT-PCR tests to detect all potexviruses and
      tobamoviruses, and then used these, together with a previously reported pair of
      primers for the Potyviridae, to screen some Australian orchid collections. Two
      orchid viruses previously reported from Australia were found; cymbidium mosaic
      potexvirus was common, but odontoglossum ringspot tobamovirus was not. In
      addition the recently described ceratobium mosaic potyvirus was found to be
      common, and three other novel potyviruses were also found.

PMID- 9763131
TI  - A simplified immunoassay based on measles virus recombinant hemagglutinin protein
      for testing the immune status of vaccinees.
AB  - Simplified tests based on recombinant antigens are considered to be important for
      monitoring immunity against measles virus (MV). The hemagglutinin protein (H) is
      the main target for neutralising and protective antibodies. We produced a
      recombinant MV-H protein, in a high-yield mammalian expression system based on
      the Semliki Forest virus replicon. The antigenicity of this recombinant protein
      was investigated with monoclonal antibodies and its suitability for measuring the
      immune status of vaccinees was tested in a large cohort by ELISA (H-ELISA). The
      results were evaluated against neutralisation (NT) and hemagglutination
      inhibition (HI) titers and MV-specific IgG measured in a commercial whole-virus
      based ELISA (MV-ELISA, Enzygnost). The H-ELISA correlated better with HI (r=0.78)
      and NT titers (r=0.80), than the MV-ELISA (HI, r=0.58; NT, r=0.59). In contrast
      to the MV-ELISA, the H-ELISA detected no false-positive sera (P < 0.02) and the
      number of false-negative sera was significantly lower in the H-ELISA than in the
      MV-ELISA (4/378 vs. 15/378; P < 0.025). The performance of the H-ELISA did not
      deteriorate significantly when, instead of background corrected net values,
      uncorrected raw O.D. values of the H-antigen were considered, or when early time
      points (30 min) were evaluated. These results demonstrate that the recombinant H
      ELISA detects efficiently non-immune individuals among vaccinees, despite their
      relatively low MV-antibody levels. A simplified format with single value
      measurements did not result in loss of sensitivity or specificity and its
      performance compared favorably with commercial ELISAs based on whole virus.

PMID- 9763133
TI  - A new and simple method for concentration of enteric viruses from water.
AB  - A new type of electropositive filter media particle was tested to adsorb
      bacteriophage f2 and enteric viruses from tap water. 3 x nutrient broth (pH 7.2)
      was used to elute the adsorbed viruses, and the eluate was reconcentrated by
      polyethylene glycol (Mw 6000) precipitation with a final concentration of 10%
      (wt./vol.). The adsorption of bacteriophage was reliable and efficient, and not
      affected by the pH value, temperature, turbidity and organic materials in water.
      This method gave a recovery of Polio 1 virus 96.0% for small-volume tap water;
      88.7% for large-volume water; and gave a comparable recovery of HAV, Coxsackie B3
      and Echo 7 from tap water. The concentration method need not acidify virus
      containing water, add exogenous multivalent cation salts, or require expensive
      equipment.

PMID- 9763132
TI  - Human monoclonal anti-HCMV neutralizing antibody from phage display libraries.
AB  - Human cytomegalovirus (HCMV) infection in immunocompromised patients causes
      considerable morbidity and mortality. Although ganciclovir prophylaxis reduces
      the incidence of HCMV disease, severe side effects raise serious problems. Thus,
      the development of new strategies for prophylaxis are clearly needed, and human
      monoclonal antibodies offer a potential alternative. We describe the cloning,
      using the phage display system, of a recombinant human Fab fragment against HCMV.
      A phage display library with 4 x 10(6) clones was panned three times against
      lysates of HCMV-infected cells, and screened by ELISA. Of six antigen-binding
      clones, one monoclonal antibody reacted strongly to HCMV. In immunostaining
      analysis, this Fab was able to stain HCMV-infected cells from 24 h post-infection
      (pi) through to 96 h pi, but not at 6 h pi. In the presence of cytosine
      arabinoside, HCMV-infected cells were not stained, even at 24 h pi. These results
      indicate that an HCMV protein that was recognized by the Fab was synthesized in
      the late phase of infection. In addition, this Fab exhibited neutralizing
      activity: at 1 microg/ml it reduced HCMV plaque formation by 50%. The Fab was
      able to neutralize three HCMV strains, but it did not neutralize HSV-1 or -2
      infection.

PMID- 9763134
TI  - Differentiation among isolates of prunus necrotic ringspot virus by transcript
      conformation polymorphism.
AB  - A method based on differences in electrophoretic mobility of RNA transcripts made
      from polymerase chain reaction (PCR) products was used for differentiation among
      virus isolates. A T7 RNA polymerase promoter was attached to amplified prunus
      necrotic ringspot virus (PNRSV) sequences by PCR. The PCR products then served as
      a template for transcription. Single-stranded transcripts originated from
      different PNRSV isolates varied in electrophoretic mobility in polyacrylamide
      gels, presumably because of transcript conformation polymorphism (TCP). This
      procedure was applied for the differentiation of PNRSV isolates.

PMID- 9763135
TI  - Total chemical synthesis of the 3' untranslated region of the hepatitis C virus
      with long oligodeoxynucleotides.
AB  - Hepatitis C Virus (HCV) is the major causative agent of chronic hepatitis. Since
      it has been difficult to obtain full-length cDNA clones of HCV including the 3'
      untranslated region (UTR) that give rise to replication competent virus, we
      generated the 3'UTR by a modified protocol of total chemical synthesis (TCS) with
      overlap-extension-PCR using four long oligodeoxynucleotides. A synthetic cDNA
      fragment of about 340 nucleotides (nt) in length was generated, subcloned and
      sequenced. This approach represents a rapid and easy alternative to RT-PCR from
      infectious serum and may be a highly valuable method to generate partial cDNA
      clones of HCV and other viruses including defined variants.

PMID- 9763136
TI  - Dysfunctional filtering blebs.
AB  - Guarded filtration surgery, is commonly used to control the intraocular pressure
      (IOP) in glaucomatous patients. Filtration surgery lowers the IOP by creating a
      fistula between the inner compartments of the eye and the subconjunctival space
      (i.e., filtering bleb). There are several options to improve the function of
      filtering blebs and to prevent their failure. However, improvement of IOP control
      after guarded filtration procedures is associated with a higher frequency of bleb
      related complications. Early (e.g., bleb leak, excessive filtration, flat
      anterior chamber, filtration failure) and late (e.g., bleb leak, excessive
      filtration and hypotony, symptomatic blebs, bleb encapsulation, filtration
      failure, bleb infection) complications associated with filtering procedures
      should be managed adequately to prevent further problems. Techniques to improve
      the function of filtering blebs and to treat postoperative complications have
      progressed over the past decade.

PMID- 9763137
TI  - Conjunctival melanoma in the black population.
AB  - Melanoma of the conjunctiva is a rare, unilateral malignancy primarily affecting
      middle-aged whites; the annual average age-adjusted incidence rate is 0.012 per
      100,000 population. Although conjunctival melanoma in the black population is
      extremely rare, cases have been reported. Melanoma of skin in blacks has a
      predilection for nonsun-exposed, nonpigmented sites such as mucous membranes,
      palms, and soles. Primary acquired melanosis may lead to the development of
      melanoma even in blacks. Primary acquired melanosis in the black population may
      be difficult to differentiate from racial melanosis clinically and
      histopathologically. Early diagnosis through awareness and education can help
      improve the survival of black patients with conjunctival melanoma.

PMID- 9763139
TI  - Surgical correction of moderate myopia: which method should you choose? I. Radial
      keratotomy will always have a place.
AB  - This set of "Viewpoints" articles examines the relative merits of radial
      keratotomy (RK), photorefractive keratectomy (PRK), and laser assisted in-situ
      keratomileusis (LASIK). Drs. Rowsey and Morley review advances in RK techniques,
      long-term results, and complications, and explain why RK will remain a viable
      method for correction of moderate myopia, notably its minimal cost. Drs. Steinert
      and Bafna review both PRK and LASIK, discussing techniques and results and
      comparing their advantages and disadvantages with each other and with RK. Dr.
      Dutton, as "Viewpoints" section editor, summarizes clinical, technologic, and
      economic aspects of all three techniques, concluding that all will find a place
      among refractive surgeons for some time to come.

PMID- 9763138
TI  - Age-related macular degeneration: a review of experimental treatments.
AB  - Age-related macular degeneration (AMD) is the leading cause of irreversible
      visual loss in the USA. Laser photocoagulation of choroidal neovascular membranes
      (CNVMs) in exudative AMD is currently the only well-studied and widely accepted
      treatment modality. It is beneficial for only a small minority of patients who
      show well-demarcated "classic" CNVMs, and it destroys normal retinal tissue,
      creates a scotoma, and is associated with an unacceptably high CNVM persistence
      and recurrence rate. Consequently, investigators have attempted to develop new
      modalities for treatment of CNVMs. These treatment modalities can be grouped into
      four major categories: photodynamic therapy; pharmacologic inhibition of CNVM
      formation with antiangiogenic agents; surgical intervention, including excision
      of subfoveal CNVMs; and radiation therapy. All of these experimental treatment
      modalities are directed toward destroyiing CNVMs, the end result of the exudative
      process, and all have limitations. The ideal treatment of the future must be
      based on the pathogenesis of the disease at a stage well before CNVMs develop.
      Investigations in nonexudative AMD are currently focusing on several major areas.
      Epidemiologic factors, such as genetics, sunlight, and nutrition, are being
      evaluated in several large studies, including the Age-Related Eye Disease Study,
      with the possibility of ultimately limiting the risk of AMD through behavior
      modification. Laser treatment of drusen is being evaluated as a means of limiting
      the risk of CNVM formation, although mixed results have been reported in the
      small number of studies to date. Choroidal perfusion abnormalities have been
      described in AMD, and some investigators postulate that altering blood flow may
      limit the risk of CNVM formation. No perfusion-treatment trials have been
      completed to date.

PMID- 9763140
TI  - Unilateral eyelid ptosis and a red eye.
AB  - A 56-year-old woman presented with a unilateral ptosis induced by a nonembedded
      soft contact lens of approximately 2 years' duration. The unilateral ptosis most
      likely resulted form localized inflammation and the physical presence of the soft
      contact lens. The patient's symptoms resolved completely after double lid
      eversion and lens removal.

PMID- 9763141
TI  - A remembrance of Edward Vail Lapham Brown.
AB  - E. V. L. Brown's ophthalmic legacy is based on his clinical research
      accomplishments, including his research centered around the causes of uveitis and
      his exhaustive studies on refractive errors in childhood, as well as his devotion
      to teaching, training a corps of carefully trained observers who were meticulous
      in their diagnostic techniques and surgical skills. This article presents a brief
      history of E. V. L. Brown's life and recreates what it was like to be a resident
      under this distinguished ophthalmologist at the University of Chicago Eye Clinic
      50 years ago.

PMID- 9763142
TI  - Strain rate as a controlling influence on adaptive modeling in response to
      dynamic loading of the ulna in growing male rats.
AB  - To test the hypothesis that the rate of change of strain to which a bone is
      subjected is an important determinant to the subsequent functionally adaptive
      modeling response, the ulnae of growing male rats were subjected to dynamic axial
      loading in vivo for a short period each day over 2 weeks. Due to the longitudinal
      curvature of the ulna, such axial loading leads to both compression and bending.
      The left ulna in three groups of rats was loaded cyclically between 1 and 20 N in
      a trapezoidal pattern to produce dynamic, longitudinal compressive strains of 
      0.004 (-4000 microstrain) at the medial midshaft with one of three strain rates:
      low (+/-0.018 sec(-1); n = 7); moderate (+/-0.030 sec(-1); n = 7); and high (+/
      0.100 sec(-1); n = 8). These strain rates span the range recorded from strain
      gauges bonded to the bone at this site during a variety of normal activities. At
      the end of the experiment, the loaded ulnae were slightly, but significantly,
      shorter than their contralateral controls (2.7% to 5.6% mean change in length; p
      < 0.0001). This effect was most marked at lower strain rates, associated with an
      increased load-bearing time. The pattern of adaptive modeling along the bone
      shaft was similar for all groups, each showing a reduced rate of periosteal
      expansion proximally, and increased periosteal new bone production distally. This
      distal increase was achieved through enhanced periosteal bone formation on the
      lateral (tension) cortex, and arrest of resorption, with conversion to formation
      on the medial (compression) surface. The modeling response to axial loading
      therefore involves complex location-dependent increases and decreases in both
      formation and resorption. The high-strain-rate group demonstrated a 54% greater
      osteogenic response than the moderate-strain-rate group, which in turn showed a
      13% larger response than the low-strain-rate group. Rate of strain change is
      therefore a major determinant of the adaptive osteogenic/antiresorptive response
      to mechanical load. Across the physiological range, a high rate of strain change
      provides a greater osteogenic stimulus than the same peak strain achieved more
      slowly.

PMID- 9763143
TI  - Validation of quantitative backscattered electron imaging for the measurement of
      mineral density distribution in human bone biopsies.
AB  - The measurement of bone mineral density (BMD) using X-rays is usually employed to
      monitor the mineral content in a given portion of bone. However, this method
      cannot differentiate between changes in bone volume or in degree of
      mineralization of the bone matrix. In contrast to BMD, bone mineral density
      distribution (BMDD), as measured on bone sections by quantitative backscattered
      electron imaging (qBEI), is able to distinguish differences in the degree of
      mineralization. For routine clinical research, we have validated the method of
      calibration and standardization of the backscattered electron (BE) signal. Carbon
      and aluminum were used as reference materials for BE gray levels and osteoid and
      apatite for calcium concentration. Experiments were performed to get knowledge
      about precision (intraassay variance-instrumental stability and interassay
      variance-reproducibility) and accuracy (standardization) of this method as well
      as the biological variance (intraindividual and interindividual) in human bone.
      On transiliac biopsies or necropsies from 20 individuals having had accidental
      death (13 females, 7 males, age 30-85 years) BMDD measurements were conducted.
      The patients' medical history as well as the histomorphology of these bones
      showed no evidence of metabolic bone disease. For instance, the standard
      deviations of the weighted mean calcium concentrations were <0.3%, <0.4%, <0.9%,
      and <2.6% of the mean for the intraassay, interassay, intraindividual, and
      interindividual variations, respectively. In addition, a mean BMDD histogram for
      transiliac bone specimens was calculated from the 20 aforementioned individuals.
      The method used allows detection of the degree of mineralization independently
      from the actual bone volume, a result that seems to be of special interest in the
      assessment of the effect of treatments for osteoporosis. The power of this
      technique is demonstrated by using bone from a patient with a metabolic bone
      disease. In this case of osteomalacia due to celiac disease, the mean calcium
      concentration in the bone matrix was reduced by 19.3% as compared with normal.

PMID- 9763144
TI  - Parathyroid hormone induces interleukin-6 heterogeneous nuclear and messenger RNA
      expression in murine calvarial organ cultures.
AB  - The cytokine, interleukin-6 (IL-6), is produced by osteoblasts and may in part
      mediate parathyroid hormone (PTH)-stimulated bone resorption. The goals of the
      present study were: (1) to examine PTH induction of IL-6 expression in 7-day-old
      mouse calvarial organ cultures; (2) to assess the role of intracellular signaling
      pathways in this model; and (3) to determine whether PTH regulates IL-6
      expression by a transcriptional mechanism. Northern blot analysis of calvarial
      RNA showed that PTH(1-34) at 0.1-100 nmol/L induced IL-6 mRNA at 0.5 h with a
      peak at 2 h. Forskolin at 10 micromol/L and 8-bromocyclic-AMP at 3 mmol/L also
      induced IL-6 mRNA with a peak at 2 h. Phorbol myristate acetate induced IL-6
      expression, whereas ionomycin and PTH(3-34) amide, an N-terminal-truncated PTH
      analog that has reduced ability to activate the cAMP-PKA pathway, were much less
      effective. PMA pretreatment of calvariae greatly blocked IL-6 mRNA induction by a
      subsequent dose of PMA and decreased induction by PTH and forskolin to a much
      lesser extent. A reverse-transcriptase polymerase chain reaction (RT-PCR) assay
      was used to measure IL-6 heterogeneous nuclear RNA (hnRNA) and mRNA. A 5' primer
      spanning exons 1 and 2 and a 3' primer complementary to exon 5 of the murine IL-6
      gene were used to detect IL-6 mRNA as a 638 bp product. A 5' primer corresponding
      to intron 4 of the murine IL-6 gene and the 3' primer were used to detect IL-6
      hnRNA as a 370 bp product. RT-PCR of total calvarial RNA showed that the
      induction of IL-6 hnRNA by PTH and other agonists was similar to their induction
      of IL-6 mRNA. These data support the conclusion that PTH transcriptionally
      induces IL-6 gene expression in murine calvarial organ cultures mainly through
      the cAMP-PKA signaling pathway.

PMID- 9763145
TI  - Effect of clodronate treatment on established bone loss in ovariectomized rats.
AB  - The ability of clodronate to prevent bone loss and weakening of bone strength was
      studied in adult rats with established osteopenia. Six-month-old female Sprague
      Dawley rats were randomized into 13 groups. One group was killed at the start of
      the study, nine groups were ovariectomized (ovx), and three groups sham-operated
      (sham). After 4 months, the ovx rats were given either clodronate or vehicle
      subcutaneously (s.c.), once a week for 3 or 6 months, the cumulative doses of
      both dosing regimens being 36, 84, and 300 mg/kg. Clodronate reduced the increase
      in bone turnover as evidenced by serum osteocalcin and urinary deoxypyridinoline.
      Cancellous bone loss was more severe in distal femur than in lumbar vertebral
      body already at 4 months after ovx. Cortical osteopenia of femoral middiaphysis
      was significant at 7 and 10 months after operation and was in accordance with the
      impaired bending strength of the femoral shaft. In the tibia, the bending
      strength was, by contrast, increased at each timepoint after ovx. In distal
      femur, higher values of cancellous bone volume (BV/TV) were found after 6 months
      of clodronate treatment than in ovx/vehicle-treated rats. In lumbar vertebrae,
      only the lowest dose of clodronate slightly counteracted the ovx-induced further
      decrease in BV/TV, but reduced, at all dosages, the impairment of lumbar
      vertebral compression strength. The maximum load of femoral neck did not differ
      between vehicle-treated ovx and sham groups after clodronate treatment, but
      clodronate reduced the weakening of femoral shaft. A further increase in the
      bending strength of the tibia was found after clodronate treatment. There was a
      positive correlation between bending strength and ash weight in both the tibia
      and the femur. Histomorphometry further showed that long-term use of clodronate
      does not impair bone mineralization or affect modeling-dependent bone formation.
      In conclusion, clodronate treatment clearly slows down the progress of bone loss
      and prevents further weakening of bone strength in femoral shaft and vertebrae,
      even though it cannot completely reverse the effects of ovariectomy-induced
      changes in established osteopenia.

PMID- 9763146
TI  - Growth hormone increases vertebral and femoral bone strength in osteopenic,
      ovariectomized, aged rats in a dose-dependent and site-specific manner.
AB  - The aim of the study was to assess the effect of growth hormone (GH) as
      restorative therapy in an aged, ovariectomized rat model with established
      osteopenia. The study was planned as a dose-response study, and four different
      skeletal sites were investigated by mechanical testing and measurements of bone
      mass and dimensions. Twelve-month-old virgin F344 rats were divided into eight
      groups with ten animals per group: (1) sham operated (sham); (2) ovariectomized
      (ovx); (3) sham + solvent vehicle (sv); (4) ovx + sv; (5) ovx + GH 50 microg/kg
      body weight/day; (6) ovx + GH 1.25 mg/kg body weight/day; (7) ovx + GH 2.5 mg/kg
      body weight/day; and (8) ovx + GH 5.0 mg/kg body weight/day. Groups 1 and 2 were
      killed after 3 months to establish that bone loss had occurred due to ovx. One
      month later, the remaining groups began 3 months of treatment, at the end of
      which the animals were also killed. The effects of ovariectomy (ovx) and GH
      therapy were measured at four skeletal sites: lumbar vertebrae; femoral
      diaphysis; femoral neck; and distal femoral metaphysis. Ovariectomy induced a
      significant loss of bone strength at all sites apart from the femoral neck. The
      loss was most pronounced at the distal femoral metaphysis. GH was able to reverse
      the ovx-induced loss of strength at the vertebral site in a dose-dependent
      manner. At the femoral diaphyseal site, GH not only reversed the ovx-induced
      changes but increased load values significantly above sham level. However, at the
      distal femoral metaphysis, which is dominated by cancellous bone, only partial
      reversal was seen after GH treatment. The lowest GH dose had no significant
      effect at any site tested. We conclude that GH treatment can reestablish
      vertebral bone loss due to ovariectomy in a dose-dependent manner. The
      restorative effect is only partial at the distal femoral metaphysis even at a
      high dose. At skeletal sites with less pronounced ovx-induced bone loss (femoral
      neck and diaphysis), GH treatment increased bone strength to sham level or above
      sham level. Therefore, the effect of ovariectomy is dependent upon the skeletal
      site investigated, and the effect of GH treatment is dependent on both the
      skeletal site and the size of the ovx-induced bone loss at this site.

PMID- 9763147
TI  - Prednisolone prevents decreases in trabecular bone mass and strength by reducing
      bone resorption and bone formation defect in adjuvant-induced arthritic rats.
AB  - We examined the effects of prednisolone (PSL) administration in normal female
      Sprague Dawley rats and adjuvant-induced arthritic rats at the age of 6 weeks.
      Rats were intramuscularly injected with PSL twice a week at doses of 0 (control),
      10, 30, 90, or 270 mg/kg body weight (b.w.). In the normal rats, serum
      osteocalcin level at 14 days and serum carboxyterminal pyridinoline cross-linked
      telopeptide of type 1 collagen (1CTP) level at 28 days in the 270 mg/kg dose
      group was lower than the respective value in control animals. The BMC and the
      trabecular bone formation rate (BFR/BS) of the lumbar body (L-4) in the 270 mg/kg
      dose group at 14 and 28 days were significantly lower than the values in the
      control rats. In the arthritic rats, however, serum osteocalcin levels in the PSL
      treated groups did not differ compared with arthritic controls. The serum 1CTP
      levels in all of the PSL-treated groups were significantly reduced at 28 days.
      The age-dependent increases in the L4 BMC, BMD, and L-3 ultimate compressive load
      values were maintained. The BFR/BS values in the 90 mg/kg and 270 mg/kg dose
      groups were significantly higher than those in the arthritic control rats. The
      trabecular osteoclast number and surface values in all of the PSL-treated groups
      were significantly lower than the values in arthritic controls. These data
      demonstrate that PSL administration prevented reduction in bone mass and strength
      of the lumbar trabecular bone in adjuvant-induced arthritic rats by reducing the
      increase in bone resorption and the decrease in bone formation at both the local
      and systemic levels.

PMID- 9763148
TI  - Effects on bone of oral hormone replacement therapy initiated 2 years after
      ovariectomy in young adult monkeys.
AB  - The purpose of this study was to determine the effects of oral estrogen
      replacement therapy with conjugated equine estrogens (CEE), alone or in
      combination with continuous medroxyprogesterone acetate (MPA), on lumbar spine
      bone mineral content (BMC) and density (BMD) and on serum chemistries in
      ovariectomized cynomolgus monkeys when therapy is initiated following a 2 year
      hypoestrogenic period. Study design was done in the form of a randomized, placebo
      controlled, nonhuman primate paraclinical trial. Monkeys were subjects in an
      experiment designed to study the effects of a lipid-lowering diet combined with
      hormone replacement therapy on atherosclerosis. Initially, they were
      ovariectomized and fed a high-fat diet for 24 months. They were then were
      allocated to three treatment groups by stratified randomization and were fed a
      diet containing reduced dietary fat for an additional 28 months. Treatment groups
      consisted of: (1) an untreated group (ovx, n = 24); (2) a CEE-treated group (CEE,
      n = 19); and (3) a CEE plus continuous MPA group (CEE + MPA, n = 20). Lumbar
      spine BMC and BMD values were measured by dual-energy x-ray absorptiometry at
      baseline and 4, 10, 16, 22, and 28 months of treatment. Serum chemistries were
      relevant to bone metabolism at 22 and 28 months. Rates of gain in BMC and BMD
      were greater (p < 0.05) in hormone-supplemented animals (groups 2 and 3) than in
      untreated ovx animals during the first 16 months of treatment, resulting in
      increased BMC and BMD measurements in these groups. Serum markers of bone
      metabolism were significantly lower (p < 0.05) in the hormone-treated groups
      (groups 2 and 3) compared with ovx animals after 22 and 28 months of treatment,
      indicating reductions in bone turnover rate. Oral estrogen replacement with CEE
      at doses similar to those taken by women leads to significantly increased BMC and
      BMD in monkeys, even when therapy is begun 2 years after ovariectomy. Most of the
      increase occurred during the first 16 months of treatment. The addition of MPA to
      the CEE regimen provided no additional benefit.

PMID- 9763149
TI  - Allelic variation at the interleukin-1 receptor antagonist gene is associated
      with early postmenopausal bone loss at the spine.
AB  - Genetic factors play an important role in determining bone mineral density (BMD)
      in later life, with the genetic influence mediated through effects on both peak
      mass and on age- and menopause-related bone loss. At menopause there is an
      increase in the production and activity of various cytokines and growth factors
      within the bone microenvironment. The activity of interleukin-1 (IL-1), a
      powerful stimulant of osteoclastic bone resorption, is increased in estrogen
      deficient states with increased production of IL-1 and inhibition of the IL-1
      receptor antagonist (IL-1ra). Treatment with IL-1ra blocks the bone loss
      associated with ovariectomy in animals and the IL-1 receptor antagonist gene (IL
      1RN) is therefore a potential candidate gene for the regulation of postmenopausal
      bone loss. We examined the relationship between annual rates of change in BMD
      over 5 years and an 86 bp variable number tandem-repeat polymorphism of the IL
      1RN gene in 108 early postmenopausal women. All women were within 5 years of a
      natural menopause at the study's onset, healthy, and not on hormone replacement
      therapy or other medication known to affect bone metabolism. BMD was measured
      annually over the 5 year study period at the lumbar spine and femoral neck using
      dual-energy X-ray absorptiometry. Three alleles were identified (A1 = 4 repeats,
      A2 = 2 repeats, A3 = 5 repeats), with five genotypes observed: A1A1 (41.7%), A1A2
      (45.4%), A2A2 (6.5%), A1A3 (2.8%), and A2A3 (3.7%). For analysis, alleles were
      collapsed into a biallelic system grouping the A1 and A3 alleles. There was no
      significant relationship between the IL-1RN genotypes and baseline bone mass at
      either the spine or hip. IL-1RN genotype was significantly associated with annual
      rates of change in spinal bone mass (p < 0.05), and this finding remained
      significant after adjustment for age, weight, and baseline BMD. Carriage of at
      least one copy of the A2 allele was associated with reduced bone loss at the
      spine (mean change in BMD +/- SD: -0.81 +/- 1.46%/year) when compared with
      noncarriage of the A2 allele (mean change -1.38 +/- 1.48%/year), p = 0.05. We
      therefore conclude that allelic variation at the IL-1RN locus is associated with
      differential rates of early postmenopausal bone loss at the spine. Further
      research will be required to clarify the mechanisms underlying these findings and
      to determine whether this association translates into a significant long-term
      effect on BMD and fracture in later life.

PMID- 9763150
TI  - Three-dimensional confocal images of microdamage in cancellous bone.
AB  - The accumulation of microdamage in bone may contribute to loss of bone quality in
      osteoporosis, and the role of microdamage in the etiology of fatigue fractures is
      unknown. Microdamage created during testing, ex vivo, can increase the fragility
      of bone by decreasing the load necessary to cause fracture. Microdamage can also
      accumulate in vivo, but its influence on bone fragility is unknown. To date,
      stained microcracks are the only criteria to have been correlated with bone
      mechanics, leaving the influence of ultrastructural damage on bone fragility open
      for scrutiny. Staining en bloc has identified three morphological features in the
      tissue, discrete microcracks, cross-hatch staining, and diffuse staining. The
      relationship between these features and their identification as microdamage
      remains equivocal. The purpose of this study was to investigate the three
      dimensional nature of microdamage in cancellous bone and also to describe stained
      microcracks, cross-hatch staining, and diffuse staining and to determine whether
      they all relate to microdamage in bone. Laser scanning confocal microscopy that
      provides improved spatial resolution over bright-field microscopy was used to
      visualize bone damage. It was found that crack surface density was highly
      correlated with crack density (r = 0.95, p < 0.0001), suggesting that the crack
      surface of preexisting cracks increases as new cracks are formed or
      submicroscopic cracks become visible under bright-field microscopy. Cross-hatch
      staining and diffuse staining included ultra-microcracks about 10 microm in
      length. The ultra-microcracks in cross-hatch staining were organized in bands and
      surrounded by diffuse staining. This study demonstrates that damage in bone
      occurs over a wide range and that discrete microcracks, cross-hatch staining, and
      diffuse staining are all indicative of bone damage. The diffuse staining still
      evident in association with the ultra-microcracks seen in cross-hatch staining
      and diffuse staining is probably due to damage at a still smaller scale than we
      have been able to investigate.

PMID- 9763152
TI  - Comparison of two methods for measuring orientation.
AB  - At the Department of Dental Radiology of ACTA, the line fraction deviation (LFD)
      method was developed to measure orientation on radiographic trabecular patterns.
      This article explains the measurement of the LFD index of orientation in a
      downscaled model. When investigations began to produce noteworthy results, the
      need for deeper understanding of the method and the resulting diagrams increased.
      Because it had previously been applied on rather complex patterns originating
      from bone it seemed worthwhile to study simpler images as well, which might yield
      a more intuitive understanding of the diagrams. Moreover, it seemed useful to
      compare the new LFD method with the well-accepted mean intercept length (MIL)
      method. Fifty images originating from cancellous bone structures and 25 drawings
      were analyzed. The results show that the MIL method tends to produce ellipses
      (not only on images originating from bone), and also that the LFD method is more
      sensitive to anisotropy.

PMID- 9763151
TI  - Bone loss in Great Britain and Japan: a comparative longitudinal study.
AB  - Hip fracture incidence is lower in Japan than in the West. Although differences
      have been found in peak bone mass and hip geometry between white and Japanese
      populations, these do not fully explain the difference in hip fracture rates.
      Variation in the rates of involutional bone loss may be an additional
      contributing factor. We address this issue in a prospective epidemiological study
      comparing bone loss rate among elderly people in Britain and Japan. Two
      population-based studies of bone loss rate in a British and a Japanese cohort
      were performed. Annual bone loss rates were obtained for 172 Hertfordshire men
      and 143 Hertfordshire women of mean age 66 years, and a questionnaire
      administered to obtain information on known confounding lifestyle factors. Eighty
      six Japanese men and 90 Japanese women of mean age 69 years completed a similar
      study in Taiji, Japan. British men and women were heavier than Japanese men and
      women. Differences in lifestyle were also evident; the British men were less
      likely to smoke and the women more likely to consume alcohol than their Japanese
      counterparts. The British population also spent more time walking outdoors.
      Statistically significant differences between the two populations were apparent
      in baseline bone mineral density at lumbar spine (p < 0.05) and trochanter (p <
      0.001) in men and women with Japanese subjects having lower values. There were
      also significant differences in bone density at the femoral neck (p < 0.001)
      between British and Japanese males. Men gained bone at the lumbar spine over the
      follow-up period in both populations. Bone loss rates were generally greater in
      the British female population than in Japanese women: the difference was
      statistically significant at the femoral neck (p < 0.05) and femoral trochanter
      (p < 0.001). These differences all remained significant after adjustment for
      differences in age between the two populations. Japanese subjects appear to have
      lower peak bone mass, but slower bone loss rates in later life than their
      European counterparts. These differences in bone loss rate help to explain the
      relatively low hip fracture rates found in Japan.

PMID- 9763153
TI  - Declining health care provision to adolescents and the need for considering
      culturally competent interventions.

PMID- 9763154
TI  - Pediatricians' approach to the health care of lesbian, gay, and bisexual youth.
AB  - The present study investigates the complex physician-patient relationship between
      pediatrician and lesbian, gay, or bisexual youth. Sixty pediatricians completed
      the questionnaire. The respondents' answers indicated a need and desire for
      further training of pediatricians about the health care of these youth.

PMID- 9763155
TI  - Access to health care for Latina adolescents: a critical review.

PMID- 9763157
TI  - Adolescent health care experience of gay, lesbian, and bisexual young adults.
AB  - METHODS: Subjects were 102 self-identified gay, lesbian, and bisexual youth aged
      18-23 years. A confidential self-administered survey elicited demographic
      information, sexual orientation information, health care experiences, subjects'
      understanding of medical confidentiality during ages 14-18 years, and their
      suggestions for improving care to gay and lesbian adolescents. RESULTS: Two
      thirds of subjects never discussed sexual orientation with their provider but
      reported a desire to do so. Fewer than one-half of subjects remembered being
      informed about their right to medical confidentiality; those who reported being
      so informed were three times more likely to have discussed their sexual
      orientation with their provider. Over 70% of subjects who reported not being
      informed about their right to medical confidentiality stated that they would have
      been more likely to discuss sexual orientation with their provider had they been
      so informed. Only 13 of subjects had disclosed their sexual orientation to their
      health care providers. Of these, only half of the males received information on
      human immunodeficiency virus prevention. CONCLUSIONS: Health care providers may
      be failing to fully address issues of confidentiality and sexual orientation with
      adolescents, despite a decade of increased information on adolescent
      homosexuality.

PMID- 9763156
TI  - Condom use by Hispanic and African-American adolescent girls who use hormonal
      contraception.
AB  - PURPOSE: The purpose of the present study was to examine condom use by teens who
      use hormonal contraceptives [i.e., Depo-Provera, Norplant, or oral contraceptives
      (OCs)]. METHODS: This is a cross-sectional study of 578 Hispanic and African
      American female adolescents between the ages of 12 and 21 years who came to a
      reproductive health care clinic. A paper-and-pencil questionnaire which addressed
      sexual behaviors, sexual history, and communication about sexuality was
      distributed to adolescent girls attending the clinic. Several important analyses
      included only those who had been sexually active in the last 4 weeks (n = 452).
      RESULTS: Adolescents who used OCs [odds ratio (OR) 1.7], long-acting agents
      (i.e., Depo-Provera or Norplant) (OR 1.6), were less likely to have used a condom
      in the last 4 weeks than teens whose only method of birth control was condoms.
      Only those teens who had previously been diagnosed with a sexually transmitted
      disease (STD) were more likely to have used a condom (OR .67 for not using a
      condom). Overall, condom use by teens in this sample was low, with only 19%
      reporting that they "always" use a condom, and 47% of the teens who had been
      sexually active in the last 4 weeks reporting that they had not used a condom at
      least once during that time. CONCLUSIONS: This study provides data which suggest
      that adolescent girls who use hormonal contraceptives are less likely to use
      condoms than other sexually active teens. Therefore, when prescribing hormonal
      contraception to prevent pregnancy, clinicians must provide appropriate
      counseling to mitigate against the potential to increase the risk of STDs.

PMID- 9763158
TI  - The sexual practices of Asian and Pacific Islander high school students.
AB  - PURPOSE: To describe the sexual behaviors, beliefs, and attitudes of Asian and
      Pacific Islander California high school students and to compare them to other
      racial/ethnic groups. METHODS: Data were collected from an anonymous self
      administered survey of 2026 ninth to 12th graders in a Los Angeles County school
      district; 186 of the respondents described themselves as Asian and Pacific
      Islander. The survey was conducted in April 1992. RESULTS: A higher percentage of
      Asian and Pacific Islander adolescents (73%) compared with African-American (28%,
      p < .001), Latino (43%, p < .001), white (50%, p < .001), and other (48%, p <
      .001) adolescents had never had vaginal intercourse. Asian and Pacific Islander
      adolescents were less likely than other adolescents to report having engaged in
      heterosexual genital sexual activities during the prior year, including
      masturbation of or by a partner, fellatio with ejaculation, cunnilingus, and anal
      intercourse. Few students in any group reported homosexual genital sexual
      activities. Asians and Pacific Islanders who had had vaginal intercourse were
      more likely than most other groups to have used a condom at first vaginal
      intercourse, but Asians and Pacific Islanders had not used condoms more
      consistently over the prior year. Asians and Pacific Islanders were more likely
      to expect parental disapproval if they had vaginal intercourse and less likely to
      think that their peers had had vaginal intercourse. CONCLUSIONS: Asian and
      Pacific Islander high school students in one California school district appear to
      be at lower sexual risk than other racial/ethnic groups. However, a large
      minority are engaging in activities that can transmit disease and lead to
      unwanted pregnancy. Therefore, current efforts to develop culturally sensitive
      clinical and community-based approaches to sexual risk prevention should include
      Asians and Pacific Islanders.

PMID- 9763159
TI  - Delayed first pregnancy among African-American adolescent smokers.
AB  - PURPOSE: This study aimed to compare rates of adolescent pregnancy among African
      American adolescents who began smoking as adolescents with those who did not.
      METHODS: Cross-sectional data on 1042 primiparous African-American women enrolled
      in a randomized clinical trial of nurse home visitation were examined. The
      independent variable, adolescent smoking, was defined as a report of smoking
      before the age of 18 years. The outcome variable was adolescent pregnancy,
      defined as first pregnancy before the age of 18 years. Logistic regression was
      used to control for potential confounders. RESULTS: After adjustments for drug
      use, use of contraception, frequency of coitus, and sexually transmitted
      diseases, women who smoked during adolescence had a 50% lower risk of becoming
      pregnant as an adolescent [odds ratio of 0.46 (95% confidence interval [CI] 0.27
      0.76)]. When time to first pregnancy was examined as a continuous variable,
      adolescent smoking was associated with a delay in pregnancy of 22.6 months (95%
      CI 16.8-29.2). CONCLUSIONS: Teen smoking appears to be associated with a
      significantly lower rate of adolescent pregnancy among African-Americans.
      Although the nature of this relationship is unclear, this finding suggests the
      need for linkage between smoking prevention and adolescent pregnancy prevention.

PMID- 9763160
TI  - Sexual orientation, sexual behaviors, and pregnancy among American Indian
      adolescents.
AB  - PURPOSE: A recent study found a disproportionate number of pregnancies among Euro
      American lesbian and bisexual adolescents compared to heterosexual peers.
      American Indian adolescents have reported higher prevalence of
      gay/lesbian/bisexual orientations than Euro-Americans; do they also report higher
      prevalence of pregnancy? METHODS: The study assessed prevalence of teen pregnancy
      and related factors by sexual orientation among sexually experienced, reservation
      based American Indian adolescent males (n = 2056) and females (n = 1693) who
      participated in a national school-based survey in 1991. Self-reported orientation
      was classified as heterosexual, gay/lesbian/bisexual, and "unsure" of
      orientation. RESULTS: Gay/bisexual males were more likely than other males to
      report early heterosexual intercourse (<14 years), more consistent contraception,
      and a higher prevalence of abuse and running away (p < 0.05 to p < 0.0001).
      Likewise, lesbian/bisexual females were more likely to report early onset of
      heterosexual intercourse, more frequent intercourse, and running away. Sexual or
      physical abuse did not vary by orientation for females. Prevalence of pregnancy
      also did not vary by orientation (males, 18.6% gay/bisexual vs. 10.4% "unsure"
      vs. 11.8% heterosexual; females, 25.0% lesbian/bisexual vs. 22.1% "unsure" vs.
      21.9% heterosexual). For lesbian/bisexual females, no variables were
      significantly associated with pregnancy history; for "unsure" females, pregnancy
      was associated with contraceptive frequency and early onset of heterosexual
      activity. For heterosexual females, age, intercourse frequency, and physical
      abuse were associated. For gay/bisexual males, intercourse frequency, ineffective
      contraception, and physical abuse were associated with involvement in a
      pregnancy; for "unsure" and heterosexual males, most items except ineffective
      contraception were related to pregnancy involvement history. CONCLUSIONS:
      Although prevalence of pregnancy is similar, findings show group differences in
      associated risk factors by sexual orientation. Interventions to reduce pregnancy
      among American Indian adolescents should include assessment of sexual orientation
      and behavioral risk factors.

PMID- 9763161
TI  - Biplanar chevron osteotomy.
AB  - We retrospectively reviewed the results of using a biplanar chevron osteotomy
      performed on patients who presented with hallux valgus deformities with an
      increased distal metatarsal articular angle (DMAA). The study included 17 feet
      (14 patients) of 12 women and 2 men. The average follow-up was 33 months. The
      average American Orthopaedic Foot and Ankle Society Hallux Metatarsophalangeal
      Interphalangeal Clinical Rating Score was 91. Ten of the 14 patients (13 of 17
      feet) stated that they would choose to undergo the procedure again. The hallux
      valgus angle was improved from an average of 22 degrees to 18 degrees, the
      intermetatarsal angle from 11 degrees to 9 degrees, and the DMAA from 16 degrees
      to 9 degrees. We have demonstrated this procedure to be useful in the treatment
      of symptomatic bunion deformities with an increased DMAA.

PMID- 9763162
TI  - Modified Mitchell osteotomy for hallux valgus.
AB  - From 1988 to 1995, 96 patients (161 feet) underwent a modified Mitchell distal
      metatarsal osteotomy performed for mild-to-moderate hallux valgus. On AP x-rays
      of the standing foot, the average intermetatarsal angle was corrected from 15
      degrees to 9 degrees, and the first metatarsophalangeal angles were corrected
      from an average of 41 degrees to 15 degrees. Criteria for evaluation of clinical
      results included relief of pain, appearance of foot, and shoe wear. After an
      average follow-up of 38 months, the overall satisfaction rate was 92.5%.
      Complications included 13 pin tract infections, two delayed unions, and two
      correction losses. The most common late sequela was transfer metatarsalgia of the
      lesser toes, which occurred in 20 feet (12.4%), leading to some dissatisfaction.
      The Mitchell osteotomy can be used on cases with less than 20 degrees of
      intermetatarsal angle, offering a stable construct with easy postoperative care.

PMID- 9763163
TI  - Traumatic extrusion of the talus (missing talus).
AB  - Complete dislocation of the talus is an extremely rare injury. We report on a
      case that was treated according to a surgical technique described by Gunal et al.
      According to this technique, a pseudarthrosis is created between the tibia and
      the calcaneus by transposing and fixing the medial malleolus laterally and
      displacing the entire foot anteriorly. The result was considered to be initially
      unsatisfactory. At the 2-year follow-up examination, the outcome was considered
      to be satisfactory. This was attributed to preservation of motion and stability
      in the new mortise.

PMID- 9763164
TI  - Metastatic prostate carcinoma to the foot with magnetic resonance imaging and
      pathologic correlation.
AB  - Metastases to the bones of the foot from prostate carcinomas are rare and usually
      are associated with diffuse metastatic disease. The authors encountered a patient
      who presented with prostate carcinoma metastases limited to the right foot.
      Magnetic resonance imaging correlation in this case demonstrated normal marrow
      signal in the surrounding bones of the foot and increased vascularity of the
      foot.

PMID- 9763165
TI  - Effects of exercise on Achilles tendon healing in a rat model.
AB  - The effects of motion, or lack of it, on Achilles tendon healing are not well
      defined. We have recently shown that immobilization has a detrimental effect on
      tendon healing in a rat model. The aim of this experiment was to determine
      whether enforced exercise had an additional beneficial effect on the mechanical
      and functional recovery of divided Achilles tendons in rats. Male Sprague-Dawley
      rats were randomly allocated into a nonexercise and an exercise group (N = 10 for
      each group). In both groups the right Achilles tendon was surgically transected.
      The left, uninjured lower limb served as an internal control. Both groups of
      animals were housed under identical conditions with the exception that the
      exercise group swam for 15 minutes per day. Functional performance was determined
      from the measurement of hindpaw prints of walking rats preoperatively and on
      alternate postoperative days. On day 15, the animals were killed and weighed, and
      biomechanical evaluations were performed on both the injured and uninjured
      Achilles tendon constructs. There were no differences in weight at time of death.
      All animals had an initial functional deficit that returned to near-normal by day
      15. There were significant differences in the morphological and the mechanical
      properties of the healing Achilles tendon constructs at day 15 when comparing the
      injured with the uninjured Achilles tendon constructs. Supplemental exercise,
      however, had no effect on the functional or mechanical recovery of injured or
      uninjured Achilles tendons in the rat model.

PMID- 9763166
TI  - Use of ultrasonography versus magnetic resonance imaging for tendon abnormalities
      around the ankle.
AB  - A prospective study was performed on 28 patients who underwent surgery for tendon
      disorders around the ankle. Preoperatively, all patients had real-time, high
      resolution ultrasonography performed with a 7.5 or 10 mHz transducer. Twenty of
      these patients also had a preoperative magnetic resonance imaging (MRI)
      examination of the ankle. A total of 54 tendons were inspected intraoperatively,
      revealing a total of 24 intrasubstance or complete tendon tears. These surgical
      findings were compared with the ultrasound and MRI findings, from which the
      sensitivity, specificity, and accuracy were calculated for both modalities.
      Ultrasound produced results with a sensitivity measurement of 100%, specificity
      of 89.9%, and accuracy of 94.4%. MRI produced results with a sensitivity
      measurement of 23.4%, specificity of 100%, and accuracy of 65.75%. Ultrasound
      results were more sensitive and accurate than MRI in the detection of ankle
      tendon tears in our study.

PMID- 9763167
TI  - Healing times of diabetic ulcers in the presence of fixed deformities of the foot
      using total contact casting.
AB  - In a diabetic foot, ulcers can lead directly to the loss of a limb, and they may
      be life threatening if the patient is not provided effective intervention
      directed at healing. This study reports on the healing times of diabetic
      neuropathic plantar ulcers in the presence of fixed deformities of the foot using
      the ambulatory method of total contact casting (TCC). In this study, 21 subjects
      with chronic diabetes mellitus, plantar ulcers, and fixed deformities of the foot
      were put in casts, and their progress was followed until the ulcers were
      completely healed. Results indicated that all of the ulcers healed. The average
      time to healing was 67 +/- 29 days. Ulcers located in the forefoot, midfoot, and
      rearfoot healed in an average of 35 +/- 12 days, 73 +/- 28 days, and 90 +/- 12
      days, respectively. The location of the ulcer and the presence and location of a
      fixed deformity of the foot strongly correlated with and was predictive of
      healing time using TCC. The location of the ulcers and the location of the fixed
      deformities of the foot should always be considered by providers of
      rehabilitation who treat diabetic neuropathic foot ulcers using TCC.

PMID- 9763168
TI  - Charcot restraint orthotic walker.
AB  - Five patients (three with insulin dependent diabetes mellitus (IDDM), one with
      noninsulin dependent diabetes mettlitus (NIDDM), and one with hereditary
      sensorimotor neuropathy (HSMN)) with stage 1 Charcot's neuroarthropathy involving
      the midfoot and or subtalar and ankle joints were fitted with a Charcot restraint
      orthotic walker (CROW). The rationale for this orthotic management was to
      maintain a plantigrade foot for ambulation and to protect the joints and skin by
      the uniform transfer or distribution of weight over the foot until the time when
      the pathology reached the stage of coalescence. The patients were able to fully
      bear weight and to ambulate with the CROW. All patients noted varying measures of
      improvement in symptoms and function at an average 12-month follow-up. The CROW
      is a useful orthosis in the armamentarium for treating neuroarthropathy of the
      pedal joints.

PMID- 9763169
TI  - Atypical medial dislocation of the first metatarsophalangeal joint.
AB  - Medial dislocation of the great toe without fracture or sesamoid separation is an
      unusual event. We are reporting such a case which occurred in a man after a motor
      vehicle accident. The patient was treated with closed reduction and cast
      immobilization. The patient recovered all his activities after 30 days. Three
      year follow-up showed a complete recovery, clinically and radiographically, with
      only slight radiographic signs of osteoarthritis, which was present also in the
      contralateral foot.

PMID- 9763170
TI  - Posterior tibial tendon tears in young competitive athletes: two case reports.
AB  - Unlike the Achilles tendon, the posterior tibial tendon does not typically
      undergo acute rupture. We report two cases of posterior tibial tendon tears
      occurring in young, athletic individuals (<30 years old) that required operative
      intervention before the patients could return to competitive sports. We believe
      that these are the first two reports of posterior tibial tendon tears occurring
      in this population without the patient having a prior history of steroid
      injections in the tendon. The tears we observed and described at surgical
      exploration were chronic and degenerative in nature. We also comment on our
      approach to treatment of posterior tibial tendon injuries in the athletic
      population.

PMID- 9763171
TI  - Great toe neuroarthropathy: a report of two cases.
AB  - Two cases of diabetic neuroarthropathy of the great toe are presented. The
      differential diagnosis is emphasized, and the literature regarding this unusual
      site for symptomatic disease is reviewed.

PMID- 9763173
TI  - Replantation of the great toe: two case reports.
AB  - We performed two replantations of the great toe in children less than 4 years of
      age. Both cases were successful, and there was no complaint of pain or
      disturbance in gait, postoperatively. Good results seemed to be based on mobility
      of the metatarsophalangeal joint and on sensation in the replanted toe. In our
      opinion, all traumatic amputations of the great toe in children should be
      replanted, if the conditions of the foot and amputated toe allow vascular and
      neural reattachment.

PMID- 9763172
TI  - Delayed aseptic swelling after fixation of talar neck fracture with a
      biodegradable poly-L-lactide rod: case reports.
AB  - A 63-year-old woman complained of acute swelling and pain in her ankle at 15
      months, after fixation of a talar neck fracture with poly-L-lactide rods.
      Roentgenographic and laboratory data revealed no abnormalities, but T1-weighted
      magnetic resonance imaging showed a diffuse area of low intensity in the talus.
      After nonweightbearing for 1 month, local findings had disappeared and the area
      of low intensity shown by magnetic resonance imaging had decreased without
      surgical treatment. Although there have been some reports of aseptic swelling or
      synovitis after fixation of a fracture with polyglycolide rods or screws, there
      has been no report of such cases with poly-L-lactide rods or screws.

PMID- 9763174
TI  - Fractures of the lateral process of the talus: two case reports and a
      comprehensive literature review.
AB  - Fractures of the lateral process of the talus are frequently overlooked and
      should be considered in the differential diagnosis of patients with acute and
      chronic ankle pain. Early diagnosis is emphasized in all series reviewed in the
      literature to prevent long-term complications. Thorough radiographic evaluation
      is necessary to determine the need for operative vs. nonoperative management.
      Small nondisplaced fractures are treated with cast immobilization, whereas large
      or displaced fractures usually require open reduction and internal fixation.
      Comminution of fragments may necessitate surgical excision. To achieve the best
      possible results, a timely diagnosis is required, and it is our belief that early
      treatment has better overall results.

PMID- 9763175
TI  - Hyperdorsiflexion sign in tears of the tendo Achillis.

PMID- 9763176
TI  - Treatment of diabetic (neuropathic) foot ulcers with two-stage debridement and
      closure.

PMID- 9763177
TI  - Acoustic analysis of induced vocal stress by means of cognitive workload tasks.
AB  - The purpose of this study was to determine the acoustic effects on voice of three
      tasks of cognitive workload and their possible relationship to stress. Acoustic
      analysis was used to measure stress and workload in four experimental tasks and
      two experiments. In the first experiment, subjects performed cognitive workload
      tasks under a stressful condition, performing the tasks as rapidly as possible
      without errors and with the knowledge that any errors committed would reduce
      their grade in a course. The second condition was to perform the same tasks but
      without the condition of stress related to the final grade. Four testing
      conditions were included. One was a baseline measure in which subjects spelled
      the Spanish alphabet. The second was the reading of a tongue twister, the third
      was the reading of a tongue twister with delayed auditory feedback, and the
      fourth was spelling the Spanish alphabet in reverse order. In each condition the
      subjects prolonged the vowel /a/ for, approximately 5 sec. All subjects performed
      a test to determine their overall level of anxiety. The results suggest that in
      conditions of experimentally induced stress there is an increase in the
      fundamental frequency (F0) relative to baseline, an increase in jitter and
      shimmer, an increase in the high-frequency harmonic energy, and a decrease in
      spectral noise.

PMID- 9763178
TI  - Vocal fold strain and vocal pitch in singing: radiographic observations of
      singers and nonsingers.
AB  - The relationship between vocal fold strain and vocal pitch in singers and
      nonsingers singing a rising pitch series has been indirectly investigated by
      means of lateral radiographs. Nonsingers tend to exhibit more strain than
      singers. To standardize the degree of strain, an index of strain per semitone is
      proposed. The semitone strain indicates the average amount of strain per 1
      semitone of pitch increase or decrease. The index has been shown to be affected
      by several factors: gender, singing training, singing technique, voice class,
      age, and status of muscle function. Observations suggest that similar groups of
      individuals occupy different positions on the stress-strain curve, indicated by
      their semitone strain values.

PMID- 9763179
TI  - Laryngeal airway resistance in teachers with vocal fatigue: a preliminary study.
AB  - A noninvasive pressure-flow technique was used to compare laryngeal airway
      resistances in nine female classroom teachers with symptoms of vocal fatigue and
      seven teachers without symptoms of vocal fatigue. Data were collected two times
      per day on the Monday, Wednesday, and Friday of a typical work-week. No
      significant between-group differences were found, but two within-group
      differences were notable. Airflow in the fatigued subjects decreased across the
      sampling period (p = .0009). In the controls, air pressure increased across the
      sampling period (p = .021). These findings suggest that both groups may have
      reacted to vocal demands during the week by employing two different strategies to
      maintain habitual laryngeal airway resistance: laryngeal adjustments alone or
      laryngeal adjustments plus increased respiratory drive. The first strategy,
      employed by the fatigued subjects, may have been less efficient, thereby
      provoking conditions associated with their vocal fatigue.

PMID- 9763180
TI  - Direct measurement of subglottic pressure and laryngeal resistance in normal
      subjects and in spasmodic dysphonia.
AB  - This study tested the accuracy of indirect methods of measurement of laryngeal
      airway resistance in normal subjects and in spasmodic dysphonia (SD). The
      indirect method assumes that subglottic air pressure remains constant during the
      voiced segment of a syllable. In this study subglottic air pressure was directly
      measured via puncture of the cricothyroid membrane in seven normal subjects and
      seven subjects with SD. The true laryngeal airway resistance was calculated and
      compared with airway resistance measured using indirect techniques based on
      intraoral air pressure. In five of the seven normal subjects, subglottic air
      pressure did not remain constant during the voiced segment. As a result, the
      error produced using indirect method of calculating average laryngeal resistance
      for the normal subjects varied from -44% to +50%. For SD subjects the error
      ranged from -49% to +22%. In general, the indirect technique overestimated
      laryngeal airway resistance in normal subjects and underestimated the resistance
      in subjects with SD.

PMID- 9763181
TI  - Laryngeal adduction in resonant voice.
AB  - The primary question in this study was whether subjects with nodules and subjects
      with healthy larynges would produce "resonant voice" with a similar laryngeal
      configuration. A second question regarded whether the electroglottographic closed
      quotient (EGG CQ) could be used to noninvasively distinguish resonant from other
      voice types. Twelve adult singers and actors served as subjects, including 6
      persons with healthy larynges and 6 persons with nodules. Performers were used as
      an attempt to maximize token validity and stability. Subjects produced repeated
      tokens of resonant, pressed, normal, and breathy voice during sustained vowels.
      Laryngeal adduction was directly estimated using blinded, ordinal, visual
      perceptual ratings based on videoscopic views of the larynx. EGG CQs were further
      calculated based on separate trials. The perceptual ratings indicated that
      subjects in both groups produced resonant voice with a barely adducted or barely
      abducted laryngeal configuration that was distinct from configurations for
      pressed and breathy (but not normal) voice. Previous literature suggests that
      this configuration may be relevant in many cases of voice therapy (1). Average
      CQs distinguished resonant from pressed voice, but inconsistently distinguished
      resonant from breathy voice. Further CQs were reliably different across healthy
      subjects and subjects with nodules. Thus, the utility of this measure to
      noninvasively estimate resonant voice may be limited, particularly without
      ongoing subject-specific calibration procedures.

PMID- 9763182
TI  - Voice problems among teachers: differences by gender and teaching
      characteristics.
AB  - This study describes the effects of teaching activities on voice problems in male
      (n = 274) and female teachers (n = 280). Over 38% of the teachers studied
      complained that teaching had an adverse impact on their voice and 39% of those
      had cut back teaching activities as a result. Compared to males, female teachers
      more frequently reported a voice problem (38% vs. 26%, p<.05), acute (p<.05), and
      chronic (p<.05) voice problems, six specific voice symptoms, and five symptoms of
      physical discomfort. However, there were no gender differences in the perception
      that a voice problem adversely affected their current or future teaching career.
      For every type of course taught, women had a higher probability of reporting
      voice problems compared to men: odds ratio (OR) = 1.7-2.1. Compared with other
      courses, the teaching of physical education also was associated with an increased
      risk of developing a voice problem (OR = 3.7, 95% CI: 1.4-9.4) independent of
      gender, age, hours/day, or years taught. This is the first study to show that in
      the same occupation, females report a higher frequency of vocal symptoms than
      males even when teaching characteristics and years employment are similar.

PMID- 9763183
TI  - Unilateral cricothyroid contraction and glottic configuration.
AB  - It is frequently stated that unilateral cricothyroid muscle (CT) paralysis can be
      diagnosed by physical examination, noting rotation of the glottis, and shortening
      and vertical displacement of the ipsilateral vocal fold. These signs, however,
      are inconsistently observed, and there is considerable controversy regarding the
      direction of glottic rotation. To determine the effects of CT contraction on
      three-dimensional glottic configuration, we performed computerized tomography on
      cadaver larynges before and after simulated CT contraction. Radiopaque makers
      were used to compute distances. Unilateral CT contraction equally increased the
      length of both membranous vocal folds, and rotated the posterior glottis less
      than 1 mm. CT contraction neither adducted the vocal processes, nor significantly
      their altered vertical level. These results suggest that unilateral CT paralysis
      cannot be diagnosed on the basis of any clinically apparent change in glottal
      configuration.

PMID- 9763184
TI  - Voice range in superior laryngeal nerve paresis and paralysis.
AB  - Evaluation of Physiologic Frequency Range (PFR) and Musical Frequency Range (MRP)
      of Phonation was performed on 56 adults (singers and nonsingers) presenting with
      superior laryngeal nerve (SLN) paresis or paralysis confirmed by laryngeal
      electromyography. The most common etiology was neuritis (69.7%), followed by
      iatrogenic and unknown causes,each accounting for 10.2% of cases, and finally
      trauma (8.9%). Both female and male singers with SLN paresis or paralysis had
      significantly higher PFR and MPR than nonsingers. Female classical singers
      presented PFR and MPR of up to 10 semitones (ST) higher than nonclassical singers
      and nonsingers. The lowest PFR and musical ranges were found in patients with SLN
      paresis associated with recurrent laryngeal nerve paresis or paralysis. The
      authors suggest that voice range measurement is a useful parameter for analyzing
      the effects of SLN paresis or paralysis on voice and that it may also assist in
      measuring outcome following voice therapy.

PMID- 9763185
TI  - The vocal athlete and endotracheal intubation: a management protocol.
AB  - Endotracheal intubation is associated with significant laryngeal sequelae that
      range in severity from mild hoarseness to life-threatening tracheal stenosis.
      Although the most severe trauma appears to be related to prolonged intubation,
      even short-term intubation (< 1 day) can adversely affect laryngeal and vocal
      function. Concern is warranted for all intubated patients, but particularly for
      the vocal athlete whose livelihood and identity depend on optimal vocal function.
      It is proposed that the vocal athlete faced with endotracheal intubation risk
      warrants careful multidisciplinary management. A number of intubation risk
      factors have been identified in the literature; however, clinical management of
      vocal athletes who undergo intubation has not been addressed. In medical settings
      where adverse intubation outcomes can lead to litigation, this clinical
      management protocol is expected to improve the probability of favorable voice
      outcome following endotracheal intubation.

PMID- 9763186
TI  - Laryngeal injuries after short- versus long-term intubation.
AB  - Forty-five patients were seen over a 5-year period with laryngeal injuries
      following endotracheal intubation (ETI). The mean duration of ETI was 5.6 days (2
      hours to 37 days). Patients intubated for less than 24 hours were most likely to
      present with a vocal fold immobility or an anterior glottic web. Long-term
      intubation was associated with the development of subglottic stenoses and
      granulomas. Patients with vocal fold immobility were seen more often after ETI
      for surgical reasons and had a significantly higher incidence of previous
      intubation and tobacco usage. Subglottic stenoses were seen in younger patients
      intubated for medical reasons and associated with nasogastric tubes and longer
      periods of intubation.

PMID- 9763187
TI  - Voice changes in women treated for endometriosis and related conditions: the need
      for comprehensive vocal assessment.
AB  - Hormonal treatments which have an androgenic effect have the potential to cause
      vocal changes. The changes in vocal fold structure and voice quality are
      considered to be irreversible. To date, studies have documented subjective vocal
      changes or documented single cases without detailed, baseline voice assessments.
      The impact on laryngeal function of women taking these androgenic treatments
      requires further detailed, objective assessment. The need for increased awareness
      of the actions of androgenic hormones on womens' voices, and the benefits of a
      thorough voice assessment are discussed.

PMID- 9763188
TI  - The biomechanics of the medialization laryngoplasty (thyroplasty type 1) in an ex
      vivo canine model.
AB  - The biomechanics of medialization laryngoplasty are not well understood. An
      excised canine larynx model was used to test the effects of various sized silicon
      implants. The vocal fold length, position, and tension were measured.
      Medialization laryngoplasty did not affect vocal fold length. At the mid
      membranous vocal fold, larger shims resulted in greater medialization and
      tension. Medialization laryngoplasty neither medialized nor stiffened the vocal
      process to resist lateralizing forces. We conclude that medialization
      laryngoplasty provides bulk and support for defects of the membranous region of
      the vocal fold, but does not appear to close a posterior glottal gap. The
      selection of a surgical procedure to treat glottal incompetence should take into
      account the unique biomechanical properties of the anterior (membranous vocal
      folds) and posterior (cartilaginous portion) glottis.

PMID- 9763189
TI  - Laryngeal rebalancing for the treatment of arytenoid dislocation.
AB  - In almost every type of functional laryngeal operation a successful result hinges
      on the surgeon's ability to control the muscular and ligamentous forces that act
      upon the vocal folds. Most of the time these forces are small in relation to the
      manipulations and resections performed. Occasionally, the forces are significant
      relative to the problem encountered, resulting in a failed surgery. Of all the
      many conditions that fit in to this latter description, perhaps the best example
      in arytenoid dislocation. Dislocation of the arytenoid is usually secondary to
      trauma with the majority of reported cases resulting from some type of anesthetic
      misadventure. Two types of dislocation have been described, anteromedial and
      posterolateral, each with a different mechanism of causation. This paper concerns
      itself with the more common anteromedial variety and its treatment using
      botulinum toxin.

PMID- 9763190
TI  - Does botulinum toxin alter laryngeal secretions and mucociliary transport?
AB  - Localized botulinum toxin injection disrupts cholinergic transmission and has
      potential to cause focal dysautonomia. Mucociliary transport and laryngeal
      secretions are thought to be mediated in part by autonomic, cholinergic
      transmission. We questioned whether patients who receive Botox injection for
      adductor spasmodic dysphonia (ADSD) report postinjection symptoms possibly
      related to altered mucociliary clearance or laryngeal secretions. Medical
      histories, audiotaped interviews, and symptom ratings were retrospectively
      examined for 29 patients with ADSD who were followed after one or more Botox
      injections. Patients had received bilateral, percutaneous Botox injections of 2.5
      units using an EMG-guided approach. One or more weeks after injection, four
      patients reported either burning, tickling, or irritation of the larynx/throat,
      excessive thick secretions, or dryness. Symptoms recurred with subsequent
      injections in two patients and were not associated with swallowing difficulty.
      These symptoms are consistent with, but not diagnostic of, the known effects of
      botulinum toxin on cholinergic, autonomic transmission.

PMID- 9763191
TI  - Towards a unified theory of immunity: dendritic cells, stress proteins and
      antigen capture.
AB  - In less than a decade, the archetypal view that the immune system exists
      primarily to distinguish "self" from "non-self" has been replaced by the paradigm
      that the immune system functions primarily to distinguish dangerous from non
      dangerous antigens. This change is in part due to the recent reassertion of the
      importance of so-called innate immunity, which consists of non-specific
      components of the immune system such as macrophages that are active prior to
      exposure to antigens (In contrast, so-called acquired immunity depends upon the
      generation of B and T lymphocytes that are produced after exposure to the
      antigens and are specific for the antigens). The paradigm shift is also due to
      the recent proposal of the "danger model" of the immune system, which provides a
      conceptual mechanism by which the immune system might distinguish dangerous from
      non-dangerous antigens. The role of dendritic cells (DCs) in activating T
      lymphocytes is key to both innate immunity and the danger model. The purpose of
      this commentary is to add an additional piece to the emerging picture of immune
      system function by suggesting that heat-shock, or stress, proteins play a central
      role in the activation of T lymphocytes by DCs. The uptake of stress proteins-
      whose expression is induced by monokines in the earliest phases of the innate
      immune response--by DCs might constitute a "danger" signal. However, through such
      a mechanism, DCs may capture antigens bound to stress proteins and improve their
      ability to present the antigens to other components of the immune system, such as
      cytotoxic T-cells. Invoking stress proteins to amplify the immune response in
      this manner can explain how animals can mount an effective primary immune
      response to an antigen despite having few T lymphocytes specific for that
      antigen. Finally, the "affinity-maturation" of antibody following a primary
      immune response would enable the much more efficient, specific antigen-capture by
      high affinity antibodies in a secondary immune response, resulting in a rapid and
      specific response or "memory" on re-exposure to the pathogen.

PMID- 9763192
TI  - Phosphorylation of an envelope-associated Hsp70 homolog in amyloplasts isolated
      from cultured cells of sycamore (Acer pseudoplatanus L.).
AB  - The presence of Hsp70 and Hsp60 molecular chaperones in amyloplasts isolated from
      cultured sycamore cells was analyzed by immunoblotting. Hsp70 homologs were
      located in both amyloplast envelope and stromal fractions, but no Hsp60 homologs
      were detected in any of the different suborganellar fractions. Incubation of
      whole amyloplasts or their envelope fraction with Mg2+ gamma-32P-ATP resulted in
      a rapid phosphorylation of the envelope-associated Hsp70 homolog, which
      constitutes a major target of phosphorylation in these plastids.

PMID- 9763193
TI  - Human oral mucosa studies with varying blood glucose concentration by non
      invasive ATR-FT-IR-spectroscopy.
AB  - During the last few years infrared spectrometry has been investigated as a non
      invasive clinical tool for improved understanding of in-vivo processes. Oral
      mucosa has been suggested as an especially suited subject for drug delivery and
      in vivo monitoring of endogenous body metabolites due to histological and
      physicochemical reasons. The attenuated total reflection (ATR) technique was used
      to characterize the outmost epidermal layer of human oral mucosa by means of
      Fourier-transform infrared spectroscopy. The penetration depth of the probing
      radiation in the mid-infrared fingerprint region, using a ZnSe-crystal for the
      horizontal ATR accessory, is in the order of a few micrometers so that microlayer
      information can be obtained by such a technique. Spectra of outer human lip and
      saliva components are presented for comparison. For several test persons, lip
      spectra were recorded during oral glucose tolerance tests. The individually
      varying blood glucose concentration was followed by means of frequent blood
      testing. Variability of the outmost microlayer has been studied using factor
      analysis of the ATR inner-lip spectra. There is no clear evidence that blood
      glucose concentration can be followed by ATR-spectroscopy of oral mucosa. Non
      invasive spectroscopic methods exploiting trace signals require special attention
      paid to the variability due to person-to-person differences and changes in
      physiological conditions.

PMID- 9763194
TI  - Detection of DNA amplification in human renal cell carcinoma cell lines using
      restriction landmark genomic scanning.
AB  - Gene amplification, which has often been observed in various human cancers,
      appears to be associated with the development and progression of malignant
      phenotypes. However, in renal cell carcinoma (RCC), conventional analytic methods
      requiring specific primers and probes have revealed infrequent amplification of
      known oncogenes. We attempted to determine if gene amplification was truly
      uncommon in RCC. The genomic DNAs extracted from 5 human RCC cell lines were
      examined by restriction landmark genomic scanning (RLGS), a two-dimensional gel
      analysis which allows evaluation of approximately 2,000 radiolabelled DNA
      fragments. By this method, we detected 24 distinct spots commonly amplified in at
      least 2 RCC cell lines compared to normal kidneys. Comparing the present results
      with chromosomal assigned-RLGS, approximately one half of these DNA fragments
      proved to be located on chromosome 2, 5 or 7. Our data suggest that amplification
      of unknown genes is likely to occur in RCC cell lines.

PMID- 9763195
TI  - Elevated expression of chitinase 1 and chitin synthesis in myosin II-deficient
      Saccharomyces cerevisiae.
AB  - To determine if the attached cells formed in Myosin II-deficient Saccharomyces
      cerevisiae result from deficient chitinase 1 (CTS1) expression, the activity of
      chitinase 1 was assayed. Secretion of this enzyme was not prevented by a MYO1
      gene deficiency, and soluble and cell wall-associated Cts1p activity were
      increased approximately 5-fold and 20-fold, respectively, in these cells. The
      increase in soluble activity was correlated with an increase in enzyme levels.
      Likewise, intracellular chitinase activity was increased approximately 22-fold,
      and the chitin content of cell walls was elevated 2-fold. These data suggest that
      the origin of myo1-associated phenotypes is not due to deficient chitinase
      expression and may instead be due to a deregulation of cell wall metabolism in
      these cells.

PMID- 9763196
TI  - An endogenous retrovirus with nucleic acid sequences similar to those of the
      multiple sclerosis associated retrovirus at the human T-cell receptor alpha,
      delta gene locus.
AB  - Retroviruses are suspected to be involved in the pathogenesis of autoimmune
      diseases, such as multiple sclerosis (MS). Here, we describe a complete
      cartography of a novel human endogenous retroviral sequence with a pol domain
      which shares a high homology with the pol sequence of the multiple sclerosis
      associated retrovirus (MSRV). Since this new endogenous retroviral sequence is
      located in the close vicinity of the locus of the human gene coding for the T
      cell receptor (TcR) alpha and delta chains on chromosome 14, it could be of
      potential interest for the understanding of MS pathogenesis.

PMID- 9763197
TI  - SR4987 and L1210 cell lines: two models in which cholera toxin susceptibility
      does not correlate with cAMP accumulation and ganglioside content.
AB  - The CT-mediated signaling mechanisms have been widely used as a tool for helping
      the knowledge of the more complex mechanisms regulating cell growth and
      proliferation in which gangliosides are involved as receptors and cAMP as second
      messenger. In the present study we compare the susceptibility of two murine cell
      lines (SR-4987 stromal cells and L1210 leukemic cells) to inhibitory effect of
      cholera toxin (CT) on cell growth and correlate their sensitivity to CT with
      ganglioside content and intracellular cAMP accumulation. The results indicate a
      very different response of the two cell lines to CT treatment. L1210 cells (which
      contain GM1a ganglioside) are sensitive to the inhibiting activity of CT (IC50 in
      the clonogenic assay = 10(-9) M) but no cAMP accumulation was observed after the
      treatment. SR-4987 cells (which lack GM1a) show a dramatic increase of
      intracellular cAMP without any inhibition of cell growth following the CT
      treatment until 10(-8) M. However, after SR4987 cells have incorporated GM1a they
      became susceptible to CT (with a IC50 value = 10(-11) M). The comparison of these
      results with our previous studies on WEHI-3B leukemia cells confirms the
      remarkable heterogeneity of cell sensitivity to the growth inhibition by CT by
      emphasizing that this inhibition is the final event of very different mechanisms
      in which CT binding to a specific ganglioside seems to be necessary and
      sufficient whereas cAMP accumulation may not be coupled with the
      antiproliferative effect of CT.

PMID- 9763199
TI  - A model to study c-myc and v-H-ras induced prostate cancer progression in the
      Copenhagen rat.
AB  - Normal rat prostate epithelial cells (EPYP-1) were isolated and immortalized with
      the Simian Virus-40 (SV40) large T-antigen, and transfected with the v-H-ras
      (EPYP-1-ras) and the c-myc oncogenes (EPYP-1-myc; EPYP-1-ras-myc) to serially
      create a step-wise model of tumor development in the rat prostate. Pronounced
      morphological differences were observed between EPYP-1 and the transfected
      sublines. The immortal epithelial cells (EPYP-1) maintained a cuboidal shape with
      orderly, contact mediated inhibition of growth. Oncogene transfected clones
      displayed a spindle shaped structure with multiple overlapping pseudopodia.
      Transfected cells also exhibited a greater degree of dysplasia, loss of contact
      inhibition growth and the upregulation of an epithelial tumor marker, cytokeratin
      18. All cells exhibited anchorage independent and androgen independent growth. In
      vivo, EPYP-1 cells and EPYP-1-myc and formed slowly growing non-metastatic,
      benign tumors in immune compromised mice, while EPYP-1-ras and EPYP-1-ras-myc
      transfected cells produced rapidly growing, malignant tumors in similar animals.
      This model augments the hypothesis that tumor initiation and progression can be
      caused by as few as two discrete genetic events. In addition, the "normal" rat
      prostate epithelium and transfected daughter cell lines represent a tumor model
      system with distinct, well understood genetic alterations: activation of ras and
      myc. This model will be a valuable addition to the current cell lines used in the
      investigation of prostate cancer carcinogenesis.

PMID- 9763198
TI  - Liver glycogenin activity in diabetic and adrenalectomized rats.
AB  - The glycogen concentration in liver is altered in various pathophysiologic
      states. In fasted rats, it is higher in diabetic, and lower in adrenalectomized
      rats compared to control animals. In fed rats, it is lower in diabetic, and
      little changed in adrenalectomized animals compared to controls. We were
      interested in determining whether the activity of glycogenin, a self
      glycosylating protein that initiates the synthesis of new glycogen molecules,
      could explain these differences in liver glycogen concentration. Glycogenin
      activity was measured by the incorporation of 14C-glucose from UDP-U-14C-glucose
      into an acid-precipitable product before and after amylase treatment of liver
      extracts. The glycogenin activity was similar in normal, diabetic and
      adrenalectomized fasted animals, regardless of the hepatic glycogen
      concentration. In fasted rats, glycogenin was present predominantly as the free
      form of the enzyme, i.e., not attached to an amylase-digestible glycan,
      presumably glycogen. In contrast, in fed rats, the majority, if not all of the
      glycogenin was incorporated into a glycogen-like (proteoglycan) molecule.
      Proteoglycan synthase activity, previously identified in normal fed rats, also
      was present in diabetic and adrenalectomized fed rats, and the activity was
      similar. Thus, the altered ability to store hepatic glycogen in diabetic fed and
      fasted and adrenalectomized fasted rats cannot be explained by decreases in
      glycogenin or proteoglycan synthase activities, at least as measured using the
      present assays.

PMID- 9763200
TI  - Platelet releasate treatment improves skin healing in diabetic rats through
      endogenous growth factor secretion.
AB  - Although impaired skin wound healing in diabetes is a well established
      phenomenon, virtually nothing is known of its underlying mechanism. We have
      demonstrated that diabetic skin exhibited a significant deficiency in total
      mitogenic activity, notably a diminution in FGF1, FGF2 and TGFbeta-like
      molecules. We postulated that impaired skin healing could be explained by a
      decreased expression of endogenous growth factors that could be compensated by a
      platelet releasate (PR) added in situ. Histological studies showed that PR
      treatment improved tissue repair and restored disturbed healing steps observed in
      untreated diabetic rat skin although reepithelialization was not altered. Our
      data demonstrate that PR treatment induces important modulations of the quantity
      and the kinetic of secretion of endogenous growth factors in the wounds. Although
      exogenous factors present in PR could no longer be quantified in the wounds after
      3 days, our results indicated that factors contained in PR may have: 1) a direct
      and immediate effect on the growth of neodermal cells, combined to 2) a long term
      stimulation of endogenous growth factor synthesis in situ during cutaneous wound
      healing in diabetic rats.

PMID- 9763202
TI  - The effects of ceramide and its analogues on the secretion of the mucocyst
      content of Tetrahymena.
AB  - Monoclonal antibody to Geodia lectin is bound by the mucocyst content of
      Tetrahymena. By using this (fluorescent-labelled) antibody and confocal
      microscopy, the actual state of the mucocyst (position, resting, filling or
      extruding) can be studied. Treatment with C2 ceramide and non-hydroxy fatty acid
      caused a rapid depletion of mucocyst material. Another ceramide analogue,
      psychosine caused fusion of mucocysts. In these cases--in contrast to the
      controls--the contractile vacuole was filled with mucocyst material and this was
      seen in the tubules in contact with the contractile vacuoles. Hydroxy fatty acid
      ceramide, sphingomyelin and sphingosine-1-phosphate were ineffective. As the
      former materials influence also the cytoskeleton, while the latter do not, the
      cytoskeleton is presumed to have a mediatory effect. Neither the connection of
      contractile vacuoles with tubular structures nor mucocyst fusion have been
      described before.

PMID- 9763201
TI  - Tissue distribution and subcellular localization of a G-protein activated
      phosphoinositide 3-kinase. An immunohistochemical study.
AB  - We studied by light-and electron microscopic immunohistochemical techniques the
      anatomical distribution and subcellular localization of a G-protein activated
      phosphoinositide 3-kinase gamma (PI3Kgamma) in several tissues of rat, mouse, dog
      and man. Using monospecific polyclonal antisera and monoclonal antibodies to the
      enzyme protein PI3Kgamma immunoreactivity was detected in rat and mouse
      neutrophils, prostate, kidney, exocrine pancreas, salivary glands (parotid gland)
      as well as in dog and human exocrine pancreas and parotid gland. No
      immunoreactive material was found in Langerhans islet cells and in the nervous
      tissue. Fine structural analysis of PI3Kgamma immunoreactivity revealed
      immunolabeling of the basolateral membrane of rat kidney tubular cells and
      certain cells in the parenchyma of the glandular part of rat prostate gland. Our
      morphological data suggest a possible involvement of the enzyme in cellular
      transport phenomena and a regulatory influence in secretory processes.

PMID- 9763203
TI  - Electrophysiological effects of felbamate.
AB  - Felbamate is a broad spectrum antiepileptic drug recently introduced into
      clinical practice for controlling seizures in patients affected by Lennox-Gastaut
      epilepsy, complex partial seizures or otherwise intractable epilepsies. However,
      the cellular mechanisms by which the drug exerts its anticonvulsant actions are
      not fully understood. The aim of the present article is to outline the possible
      mechanisms of action of felbamate as suggested by findings obtained with
      electrophysiological approaches.

PMID- 9763204
TI  - Anti-angiogenic effect of TGFbeta in aqueous humor.
AB  - Neovascularization is mediated by various factors in ocular tissues. Recent
      studies have emphasized the role of vascular endothelial growth factor in the
      induction of angiogenesis. We have previously reported that aqueous humor (AH)
      suppressed vascular endothelial cell growth and angiogenesis. We speculated that
      the anti-angiogenic effect of AH is mediated by transforming growth factor beta
      (TGFbeta). In order to clarify the presence of TGFbeta in bovine AH, we applied
      it on the heparin-sepharose affinity column and prepared two fractions (bound and
      unbound fractions). We measured TGFbeta concentration in each fraction and
      examined how the anti-TGFbeta antibody decreased the inhibitory effect of AH on
      human umbilical vein endothelial cell growth and on in vitro angiogenesis. We
      found the presence of TGFbeta2, but not TGFbeta1, in the heparin bound fraction,
      and the inhibitory effect was detected in the heparin-bound fraction. Anti
      TGFbeta antibody completely and dose-dependently extinguished the inhibitory
      effect of AH. We propose that the inhibitory effect of AH on endothelial cell
      growth and in vitro angiogenesis are both mediated by TGFbeta2. Our results
      indicate TGFbeta2 is normally present in AH and protects the eye tissue against
      abnormal neovascularization.

PMID- 9763205
TI  - Stereoselective metabolism of bisoprolol enantiomers in dogs and humans.
AB  - To clarify the mechanism of the species difference in the metabolism of
      bisoprolol enantiomers, in vitro metabolic studies were performed using dog liver
      microsomes and human cytochrome P450 (CYP) isoforms. The O-deisopropylation of
      bisoprolol enantiomers showed biphasic kinetics in dog liver microsomes. The
      intrinsic clearance (Vmax/Km) for O-deisopropylation of R(+)-bisoprolol was
      higher than S(-)-isomer in both high-affinity and low-affinity components. The
      R/S ratio of the intrinsic clearance in high- and low-affinity components was
      1.34 and 1.65, respectively. The inhibition studies in dog liver microsomes using
      CYP isoform-selective inhibitors indicated that the O-deisopropylation of both
      bisoprolol enantiomers was mediated via the CYP2D and CYP3A subfamily, and
      suggested that high-affinity oxidation was dependent on CYP2D. The kinds of CYP
      subfamilies in dogs, which contribute to the metabolism of bisoprolol
      enantiomers, were the same as those in humans. The intrinsic clearance for O
      deisopropylation of R(+)bisoprolol by human recombinant CYP2D6 was also different
      from that of S(-)-enantiomers (R/S:1.50). However, unlike the dog microsomes, the
      intrinsic clearance by the human recombinant CYP3A4 did not show a
      stereoselective difference. Therefore, the species difference in the R/S ratio of
      metabolic clearance for the oxidation of bisoprolol enantiomers (dog > human) is
      mainly due to the species difference in the stereoselectivity of one of the
      cytochrome P450 subfamilies (CYP3A).

PMID- 9763206
TI  - Melatonin decreases mRNA for histone H4 in thymus of young rats.
AB  - The antiproliferative properties of melatonin have been previously demonstrated
      for several normal and tumoral tissues. In a recent report we have shown that
      melatonin is able to inhibit programmed cell death in thymus both, in vivo and in
      vitro. Given that other authors have related programmed cell death and cell
      proliferation and that no previous reports on melatonin and cell division exist
      on thymus, we decide to study the possible antiproliferative effect of melatonin
      in this organ measured as the levels of mRNA for the histone H4. We found that
      melatonin inhibits cell division on thymus when administered chronically both, at
      high (500 microg/body weight) and low (50 microg/body weight) dose. We also found
      a circadian rhythm of the mRNA for histone H4, opposed to the one previously
      described for melatonin, supporting the negative regulation by this hormone of
      cell division on thymus. A single dose of melatonin (50 microg/body weight) was
      not able to decrease the levels of mRNA for H4 in the time-points studied but
      after two hours of its administration. Finally, we report the inhibitory effect
      of melatonin in the cell proliferation of Harderian gland, brain, lung and
      kidney.

PMID- 9763207
TI  - Multiple nitric oxide sources in neurogenic plasma extravasation in rat hindpaw
      skin.
AB  - The contribution of nitric oxide (NO) to capsaicin-evoked plasma extravasation
      was studied in rat hindpaw skin. Two inhibitors of NO synthase were used: 7
      nitroindazole, with a selectivity for nerve-derived NO, and the L-arginine
      derivative, N(omega)-nitro-L-arginine (L-NOARG), which is a non-selective
      inhibitor. Plasma extravasation was induced by intraplantar injection of 5
      microg/50 microl capsaicin and measured by the Evans blue leakage technique. Both
      acute and chronic administration of 7-nitroindazole significantly reduced
      capsaicin-evoked plasma extravasation in rat hind-paw skin, whereas L-NOARG
      enhanced it. This enhancement was abolished non-stereospecifically by either L-
      or D-arginine. Our results suggest that NO production from different sources
      yields a complex action in maintaining the endothelial integrity in neurogenic
      plasma extravasation.

PMID- 9763208
TI  - Diabetes-induced impairment of macrophage cytokine release in a rat model:
      potential role of serum lipids.
AB  - Diabetes (type I and type II) affects approximately 13 million people in the
      United States. Delayed and incomplete healing of wounds can be a major problem
      for diabetic patients. Macrophages are an important cell in the complex process
      of wound repair representing the major source of cytokines throughout the wound
      healing process. Cytokines mediate many of the cellular responses critical to
      timely wound repair. It has been suggested that diabetes impairs wound healing
      through disruption of local cytokine production. We previously demonstrated that
      platelet-derived growth factor B chain (PDGF-B) levels are deficient at the wound
      site of diabetic rats. In the present study, we measured the levels of several
      marker cytokines released from cultured peritoneal macrophages of diabetic,
      nondiabetic hyperlipidemic, and normal rats. The diabetic condition was
      associated with a generalized reduction of macrophage cytokine release.
      Nondiabetic hyperlipidemic animals demonstrated similar cytokine reduction
      supporting the hypothesis that elevated serum lipids are the primary determinants
      of diabetes-induced reductions in macrophage cytokine release. Thus, manipulation
      of serum lipids may be a therapeutically useful modality for controlling
      macrophage cytokine release in the inflammatory and/or wound environment.

PMID- 9763209
TI  - Ethanol-induced activation of the hypothalamic-pituitary-adrenal axis in a mouse
      model for binge drinking: role of Ro15-4513-sensitive gamma aminobutyric acid
      receptors, tolerance, and relevance to humans.
AB  - A mouse model for binge drinking has been developed in this laboratory, and
      several aspects of this model have been characterized. Many of the
      immunosuppressive effects of ethanol (EtOH) in this model seem to be mediated by
      activation of the hypothalamic-pituitary-adrenal (HPA) axis and consequent
      increases in the concentration of glucocorticoids, catecholamines, and perhaps
      other immunosuppressive mediators. The purpose of the work described here is to
      examine three important issues regarding the EtOH-induced neuroendocrine response
      in this model: 1) Are Ro15-4513-sensitive gamma aminobutyric acid type A (GABA-A)
      receptors involved in activation of the HPA axis by EtOH? 2) Does daily
      administration of EtOH produce tolerance with regard to activation of the HPA
      axis or with regard to suppression of natural killer cell activity? 3) Is the HPA
      axis activated by similar blood EtOH concentrations in humans and in the mouse
      model? Ro15-4513, a partial inverse agonist of GABA-A receptors, did not affect
      EtOH-induced increases in blood corticosterone levels. This suggests that Ro15
      4513-sensitive GABA-A receptors are not involved in EtOH-induced activation of
      the HPA axis and that inhibition of corticosterone production is not the
      mechanism by which Ro-15-4513 blocks EtOH-induced immunosuppression. To evaluate
      tolerance, mice were given a daily dose of EtOH (6.5 g/kg by gavage) or vehicle
      (water) for 10 days. Control groups received vehicle or EtOH only on the last day
      of the experiment. At the optimum time after EtOH administration serum
      corticosterone and splenic NK cell activity were measured. The results indicate
      no significant alterations in the response to EtOH of mice exposed to EtOH for 10
      days compared to those exposed only once. To compare the HPA axis response of
      mice and humans, lower EtOH dosages than generally used in our model were
      administered to mice, and the corticosterone response was compared to published
      data for humans who had similar ranges of blood EtOH levels. The results suggest
      that humans and mice exhibit activation of the HPA axis only when blood EtOH
      levels exceed approximately 0.14%. Together these results further characterize a
      mouse model for binge drinking that seems to provide a reasonable representation
      of many aspects of binge drinking in humans.

PMID- 9763211
TI  - mRNA levels of the hypoxia inducible factor (HIF-1) and DNA repair genes in
      perinatal asphyxia of the rat.
AB  - Hypoxia inducible factor 1 (HIF-1) is a transcription factor which is expressed,
      when mammalian cells are subjected to hypoxia, activating the transcription of
      genes encoding proteins thought important for maintaining oxygen hemostasis. The
      aim of the study was to evaluate HIF-1 mRNA levels in a non-invasive model of
      perinatal asphyxia (PA). Brain was taken for studies on HIF-1 alpha and beta 10
      min following the asphyctic period. To rule out influences by the redox status we
      also determined antioxidant enzyme mRNA levels for superoxide dismutase,
      catalase, glutathion peroxidase and performed electron spin resonance studies. To
      study the link to protein phosphorylation as previously proposed, we evaluated
      mRNA levels for protein kinase C. As DNA breaks were reported to occur in PA, we
      determined mRNA levels of two genes representing DNA nucleotide excision repair,
      ERCC2 and ERCC3, and a DNA repair gene involved in the repair of oxidation
      mediated DNA damage, XRCC1. mRNAs for HIF-1 were not detectable following 5-20
      minutes of asphyxia. The antioxidant enzymes did not show any changes during the
      asphyctic periods either and electron spin resonance failed to detect the
      presence of the hydroxyl radical. PKC significantly decreased with the length of
      the asphyctic period. ERCC2 and XRCC1 mRNAs were inducible during the acute phase
      of asphyxia indicating early repair phenomena. HIF-1 may not be relevant for
      periods of PA up to 20 minutes, the maximal survival time in our model. Neonatal
      factors may be responsible for that phenomenon although we cannot rule out that
      HIF-1 changes may occur at the protein level.

PMID- 9763210
TI  - In vivo and in vitro antiinflammatory activity of saikosaponins.
AB  - Buddlejasaponin I and saikosaponin 1 and 2, biologically active compounds from
      Scrophularia scorodonia and Bupleurum rigidum respectively, exert potent in vivo
      antiinflammatory effects on mouse ear edema induced by phorbol myristate acetate
      (PMA). The effects of these compounds on swelling and other inflammatory
      parameters are described. In screening for in vitro effects of saikosaponins on
      cellular systems generating cyclooxygenase (COX) and lipoxygenase (LOX)
      metabolites, we observed that most saikosaponins showed a significant effect. The
      action is more marked on LOX metabolite LTC4. Our data support the inhibition of
      arachidonic acid metabolism as one of the biochemical mechanisms that might be
      the rationale for the putative antiphlogistic activity of these saikosaponins.

PMID- 9763213
TI  - Peribronchial lymphocyte activation in bleomycin-induced lung injury.
AB  - The role of lymphocytes in bleomycin (Bleo)-induced lung injury remains obscure.
      In normal hamsters, peribronchial lymphatic tissue (PBLT) has been found to
      contain a large population of T lymphocytes responsive to interleukin 2 (IL-2)
      but not to IL-4. Lung injury induced by a single intratracheal instillation of
      Bleo in hamsters has been ameliorated by cyclosporin A (CyA). In the present
      study, using this model, PBLT-derived lymphocyte function was explored for 28
      days after Bleo instillation. Increase in PBLT lymphocytes occurred at five time
      points investigated, reaching highest values on day +7 (p < 0.0025). Cell
      proliferation in response to concanavalin A was enhanced, while IL-2 +/- the
      mitogen had no effect. In contrast to its inactivity in the normal hamster, in
      the Bleo-injured animal IL-4 alone induced T cell proliferation (p = 0.0077) on
      day +7. CyA therapy initially suppressed and delayed recovery of the number of
      lymphocytes and their activation. The results of this study suggest the existence
      of a vulnerable period in Bleo-induced lung injury and indicate that lymphocytes
      participate in the pathogenesis of the insult to the tissue. The unresponsiveness
      to IL-2 and the emergence of cellular response to IL-4 indicate immune deviation
      in PBLT-derived T cells.

PMID- 9763212
TI  - Heterologous regulation of muscarinic and beta-adrenergic receptors in rat
      cardiomyocytes in culture.
AB  - Previous work indicated that hyperstimulation of muscarinic receptors brings
      about profound changes not only in the density of the muscarinic receptors, but
      also of the beta-adrenoceptors in rat heart atria in vivo. We have now
      investigated whether a similar receptor cross-regulation occurs in cardiomyocytes
      in vitro. Cardiomyocytes from 3-4 day old rats were exposed to chemical agents on
      days 5-6 in culture. Densities of muscarinic and beta-adrenergic receptors were
      measured according to the binding of N-[3H]methylscopolamine and [ H]CGP 12177,
      respectively, to cell surface membranes and cell homogenates. Exposure of cells
      to the muscarinic agonist carbachol (1 mmol/l) brought about a profound decrease
      in the number of muscarinic receptors. The number of beta-adrenoceptors displayed
      biphasic changes, being augmented after 24 h (by 20-45% on the cell surface and
      by 29% in the homogenate) and diminished after 48 h and 72 h (after 48 h,
      decrease by 44-75% on the cell surface and by 36% in the homogenate). These
      effects of carbachol were not prevented by dimethylaminopropyl-bis
      indolylmaleimide, the inhibitor of protein kinase C. Exposure of cells to the
      beta-adrenoceptor agonist isoprenaline (0.1 mmol/l) strongly diminished the
      number of beta-adrenoceptors on the cell surface and in the homogenate. The
      density of muscarinic receptors on the cell surface was diminished by 24-43%
      after 24 h exposure to isoprenaline and unchanged after 48 h, whereas the
      concentration of muscarinic receptors in the homogenate was unchanged after 24 h
      and increased by 20% after 48 h. The isoprenaline-induced decrease in the density
      of cell surface muscarinic receptors could not be simulated by forskolin and was
      not abolished by the protein kinase A inhibitors Rp-cAMPS and HA-1004. Dibutyryl
      cyclic AMP diminished the density of cell surface muscarinic receptors more than
      that of the beta-adrenergic receptors. Our data reveal a novel phenomenon of a
      biphasic change (an increase followed by a loss) in the density of beta
      adrenoceptors during exposure of cardiocytes to carbachol. Activation of beta
      adrenoceptors brings about less conspicuous changes in the density of muscarinic
      receptors. The observed phenomena of receptor cross-regulation cannot be
      explained by simple activations of protein kinases A and C.

PMID- 9763214
TI  - A selective inhibitor of intestinal ACAT, EAB309 suppresses both intestinal and
      hepatic cholesterol output and stimulates chylomicron removal.
AB  - The effect of a novel inhibitor of acylcoenzyme A:cholesterol acyltransferase (EC
      2.3.1.26, ACAT), EAB309 (EAB) on plasma lipid metabolism was studied in
      cholesterol-fed rats. Orally administered EAB was not detected in the portal vein
      or the liver but distributed exclusively in the intestine, suggesting that this
      agent selectively inhibits intestinal ACAT. The rats were fed with either a
      cholesterol-diet or a cholesterol-diet containing 0.005% EAB (w/w) ad. libium for
      three weeks. ACAT activity in intestinal microsomes was significantly inhibited
      in EAB-treated rats. Hepatic ACAT activity was also decreased in EAB-treated
      rats, however, this was attenuated by the addition of excess cholesterol to the
      liver microsome, indicating that substrate availability is tightly associated
      with this enzyme's activity and the inhibition of hepatic ACAT by EAB is not
      direct. Incorporation of [3H]-cholesterol to cholesteryl ester (CE) in mesenteric
      lymph were markedly suppressed by EAB treatment. Chylomicrons (CMs) were doubly
      labeled with [3H]-vitamin A and [14C]-triglyceride (TG) in EAB-treated or non
      treated rats and injected into normal chow-fed rats. The CMs from EAB-treated
      rats were cleared faster from the plasma and taken up more by the liver compared
      with the CMs from non-treated rats. The content of CE in newly secreted VLDL was
      remarkably decreased by EAB treatment without affecting TG output. These results
      demonstrate that EAB, a novel inhibitor of intestinal ACAT, significantly
      suppresses both intestinal and hepatic CE output and stimulates CM removal. This
      suggests that the inhibition of intestinal ACAT can subsequently suppress hepatic
      ACAT by decreased CE delivery from the intestine to the liver.

PMID- 9763215
TI  - Enzymology of mitomycin C metabolic activation in tumour tissue: implications for
      enzyme-directed bioreductive drug development.
AB  - Mitomycin C (MMC) is the prototype bioreductive DNA alkylating agent. To exploit
      its unique properties and maximize patient responses, different therapeutic
      approaches have been investigated. Recently, the focus has concentrated on
      monitoring the levels of the proteins metabolizing the drug and relating these to
      activity in a regimen referred to as enzyme-directed bioreductive drug
      development. To be successful, it is important to understand the enzymology of
      metabolic activation not only in cell lines but also in solid tumour models. A
      general mechanism of action for MMC has now emerged that is activated regardless
      of the source of reducing equivalents, comprising three competing pathways that
      give rise to unique reactive intermediates and different DNA adducts.
      Partitioning into the pathways is dictated by chemical considerations such as pH
      and drug concentration. DT-diaphorase stands out in this mechanism, since it is
      much less effective at metabolizing MMC at neutral pH. At least five different
      enzymes can catalyse MMC bioreduction in vitro, and as many activities may be
      present in solid tumours, including a series of novel mitochondrial reductases
      such as a cytochrome P450 reductase. Competition between reductases for MMC
      appears to be based solely on protein levels rather than enzyme kinetics.
      Consequentially, DT-diaphorase can occupy a central role in MMC metabolic
      activation since it is often highly overexpressed in cancer cells. Although a
      good correlation has been observed in cell lines between DT-diaphorase expression
      and aerobic cytotoxicity, this does not hold consistently in vivo for any single
      bioreductive enzyme, suggesting revision of the enzyme-directed hypothesis as
      originally formulated.

PMID- 9763216
TI  - Skeletal muscle-specific calpain, p49: structure and physiological function.
AB  - Recent studies indicate that calpain, a cytosolic Ca2+-dependent protease,
      constitutes a large family comprising ubiquitous, tissue-specific, and atypical
      calpains. p94 is a homologue of the catalytic large subunit of calpain, expressed
      predominantly in skeletal muscle. Recently, p94 has been found to interact with
      connectin/titin, a muscle elastic protein, and its gene has been identified as
      being responsible for limb-girdle muscular dystrophy type 2A. The loss of
      function of a calpain species eventually leads to the activation of proteases
      including other calpain species responsible for muscle degradation. p94 does not
      form a complex with the small subunit of calpain (30K), but exists as a
      homodimer. This, together with other results, led us to consider a novel
      mechanism for the activation of calpain, a Ca2+-induced subunit rearrangement.

PMID- 9763217
TI  - New therapeutic prospects for the glycosphingolipid lysosomal storage diseases.
AB  - The glycosphingolipid (GSL) lysosomal storage diseases result from mutations in
      the genes that encode the enzymes required for glycosphingolipid catabolism
      within lysosomes. They are relatively rare diseases, but are frequently severe in
      terms of their pathology. Many involve progressive neurodegeneration, and in the
      most severe forms result in death in early infancy. The therapeutic options for
      treating these diseases are limited, and for the majority of these disorders
      there are currently no therapies available. To date, most research has focused on
      correcting the genetic lesion by gene therapy or by augmenting the enzyme
      activity deficient in these patients by introducing fully functional enzyme. This
      can be achieved by bone marrow transplantation or intravenous infusion of
      purified or recombinant enzyme (enzyme replacement). Gene therapy and enzyme
      replacement therapy are disease specific, and pharmacological approaches for the
      treatment of these disorders have not been fully explored. In this commentary,
      the problems associated with disease therapy are discussed, and a pharmacological
      agent (N-butyldeoxynojirimycin) is presented for the potential generic treatment
      of this family of disorders. Successful prevention of glycosphingolipid storage
      in a mouse model of Tay-Sachs disease suggests that this strategy merits clinical
      evaluation.

PMID- 9763218
TI  - Antiproliferative effect of deferiprone on the Hep G2 cell line.
AB  - Iron is an essential element in cellular metabolism and the growth of all living
      species, and is involved in DNA replication. The risk of hepatocellular carcinoma
      development is associated with an increase in iron availability. The aim of the
      present work was to investigate the effect of an oral iron chelator, deferiprone
      (CP20), on HepG2 cell-line proliferation in culture. HepG2 cell cultures were
      maintained in the absence of fetal calf serum (FCS) and in the presence or not
      (control cultures) of CP20 at the concentrations of 50 or 100 microM;
      deferoxamine (DFO) was used as an iron chelator reference. Cell proliferation was
      investigated by the analysis of DNA synthesis using [3H] methyl-thymidine
      incorporation and of the cell cycle by flow cytometry. Iron chelation efficiency
      in the culture model was studied by analyzing the effect of CP20 on radioactive
      iron uptake, intracellular ferritin level, and transferrin receptor expression.
      CP20, at the concentration of 50 or 100 microM, inhibited DNA synthesis after 48
      hr of incubation and induced an accumulation of the cells in the S phase of the
      cell cycle. Iron chelators inhibited cellular iron uptake, decreased
      intracellular ferritin level, and increased transferrin receptor protein and mRNA
      levels. Our results show that CP20 as well as deferoxamine inhibit HepG2 cell
      proliferation and block cell cycle in the S phase.

PMID- 9763219
TI  - Down-regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA levels
      and synthesis in syrian hamster C100 cells by the oxidosqualene cyclase inhibitor
      [4'-(6-allyl-ethyl-amino-hexyloxy)-2'-fluoro-phenyl]-(4-bromophenyl)-me thanone
      (Ro 48-8071): comparison to simvastatin.
AB  - In vivo inhibition of 2,3-oxidosqualene:lanosterol cyclase (OSC, E.C. 5.4.99.7)-
      the enzyme which catalyzes the cyclization of monooxidosqualene to lanosterol-
      does not result in elevated 3-hydroxy-3-methylglutaryl CoA reductase (HMGR)
      activity. This trait is attributed to increased levels of oxysterols, produced
      upon partial inhibition of OSC, that suppress HMGR and other sterol-responsive
      genes. The OSC inhibitor [4'-(6-allyl-ethyl-amino-hexyloxy)-2'-fluoro-phenyl]-(4
      bromopheny l)-methanone (Ro 48-8071) was shown earlier to lower low-density
      lipoprotein (LDL) cholesterol in hamsters with no increase in hepatic HMGR, in
      contrast to simvastatin. To delineate the regulatory mechanism(s) by which Ro 48
      8071 reduces cholesterol synthesis without raising HMGR levels, Syrian hamster
      C100 cells were incubated with either Ro 48-8071 or simvastatin, and their
      effects on cholesterol synthesis and LDL uptake, as well as on HMGR mRNA levels
      and rates of synthesis, were determined. Using RNase protection and
      radioimmunoprecipitation assays, we found that, in the absence of LDL in the
      culture medium, both HMGR mRNA levels and synthesis were reduced with
      concentrations of Ro 48-8071 inhibiting cholesterol synthesis by 50-75%, whereas
      LDL uptake was either reduced or unchanged. In contrast, simvastatin, at
      concentrations inhibiting cholesterol synthesis by the same 50-75%, increased
      both HMGR mRNA levels and synthesis, as well as LDL uptake. In the presence of
      LDL, HMGR mRNA levels and synthesis along with LDL uptake were little affected
      after incubation with Ro 48-8071. Still, simvastatin markedly increased both HMGR
      mRNA levels and synthesis in cells incubated in the presence of LDL, leaving LDL
      uptake unaffected. These data suggest that inhibition of OSC by Ro 48-8071
      results in an indirect down-regulation of HMGR mRNA levels and synthesis.

PMID- 9763220
TI  - Modifications of oxido-reductase activities in adriamycin-resistant leukaemia
      K562 cells.
AB  - Adriamycin (ADR), a well-known antitumoral drug, interacts with DNA (nuclear and
      mitochondrial) and cardiolipin. Moreover, ADR induces numerous mitochondrial
      modifications in sensitive cells. However, no results have yet been obtained as
      to the repercussions of drug effects on oxido-reductase activities in ADR
      resistant cells. To analyze mitochondrial damage induced by ADR treatment, we
      investigated lactate content, oxygen consumption, respiratory chain activities,
      and cytochrome content in ADR-sensitive K562 cells and two ADR-resistant variants
      (K562/R0.2 and K562/R0.5 cells). Biochemical investigations in ADR-resistant
      cells showed several mitochondrial modifications (in comparison to the parental
      cell line) according to the variant line and the physiologic state. More
      particularly, in K562/R0.5 cells cytochrome c (cyt c) oxidase (COX; EC 1.9.3.1)
      activity and cytochrome aa3 content dramatically decreased since cells enter into
      the stationary phase. Regardless of the number of multidrug-resistant cell
      subcultures in ADR-free medium, the cytochrome c oxidase activity in the
      stationary phase remained unchanged, indicating an irreversible effect of the
      drug. These alterations could correspond to several modifications of the nuclear
      and/or mitochondrial genome(s) following acquisition of the ADR resistance
      phenotype by K562 cells.

PMID- 9763221
TI  - Insulin-like growth factor 1 (IGF-I) effects on sex-specific cytochrome P450
      enzymes in normal and hypophysectomised male rats.
AB  - The role of growth hormone (GH) in the regulation of the sex-differentiated rat
      cytochrome P450 (CYP) enzymes has been extensively studied. However, little is
      known about the involvement of insulin-like growth factor I (IGF-I) as a mediator
      in this regulation. We wanted to study if IGF-I had effects on sex-differentiated
      CYP enzymes and to compare the effects of IGF-I to the effects of GH. IGF-I, GH
      or saline was administered continuously via osmotic minipumps to normal and
      hypophysectomised rats for seven days. After treatment, the expression of several
      sex-differentiated liver enzymes (CYP2C11, CYP2C12), the female-dominant steroid
      5alpha-reductase, and the male-dominant CYP3A2 enzyme was studied at mRNA,
      protein and/or functional levels. Our results demonstrate that IGF-I has marked
      effects on the sex-specific expression of CYP2C11 and CYP2C12. The effects of IGF
      I were similar to those of GH. In contrast, in hypophysectomised rats IGF-I gave
      effects opposite to those observed after GH treatment to normal rats on the CYP3A
      associated cortisol 6beta-hydroxylation. No effects of IGF-I on the steroid
      5alpha-reductase activity were observed.

PMID- 9763222
TI  - Purification and characterization of protease activated by sulfur mustard in
      normal human epidermal keratinocytes.
AB  - A membrane-bound protease induced by sulfur mustard in cultured normal human
      epidermal keratinocytes (NHEK) was purified and partially characterized. Maximum
      enzyme stimulation occurred at 16 hr after normal human epidermal keratinocytes
      were exposed to 300 microM sulfur mustard. Purification to homogeneity of the
      protease was accomplished by Triton X-100 solubilization, ultracentrifugation,
      and dialysis, followed by ion-exchange chromatography through DEAE-cellulose and
      finally hydrophobic column chromatography through phenyl Sepharose. Analysis of
      the purified enzyme by SDS-PAGE revealed a single polypeptide at the 80 kDa
      region. Further investigation of biochemical properties showed that a synthetic
      serine-specific Chromozym TRY peptide and the physiological protein laminin were
      good substrates for this enzyme. Moreover, this enzyme was inhibited mostly by
      the serine-protease inhibitors leupeptin and di-isopropyl fluorophosphate and not
      by the cysteine protease inhibitor E-64 or the metalloprotease inhibitor 1,10
      phenanthroline (Component H, CH), indicating the serine protease nature of this
      enzyme. This enzyme had a pH optimum in the range of 7.0 to 8.0. Amino acid
      sequencing of the purified enzyme revealed that this enzyme belongs to the
      endopeptidase family (serine protease), and is homologous with a mammalian-type
      bacterial serine endopeptidase that can preferentially cleave K-X, including K-P.
      These results suggest that serine-protease stimulation may be one of the
      mechanisms of mustard-induced skin blister formation, and that some specific
      serine-protease inhibitors may be useful for the treatment of this sulfur mustard
      toxicity.

PMID- 9763223
TI  - Differential inducibility of specific mRNA corresponding to five CYP3A isoforms
      in female rat liver by RU486 and food deprivation: comparison with protein
      abundance and enzymic activities.
AB  - The induction of cytochrome P450 3A (CYP3A) protein and mRNA by RU486 [17beta
      hydroxy-11beta-(4-dimethylaminophenyl)-17alpha-1-pro pyl-estra-4,9-dien-3-one]
      treatment and food deprivation in female rat liver was studied using Western
      blotting and competitive reverse transcription-polymerase chain reaction (RT
      PCR). CYP3A apoprotein levels increased in response to food deprivation and to
      RU486 treatment, and the combination of RU486 treatment plus food deprivation had
      an apparent additive effect. Food deprivation and RU486 treatment also caused
      increases in CYP3A1, CYP3A18, and CYP3A23 mRNA, and the combined effects of these
      treatments on each of these mRNA forms were synergistic. CYP3A2 mRNA was not
      detected in any of the treatment groups, and there was a lack of concordance
      between CYP3A9 mRNA levels and the specific messages corresponding to the other
      CYP3A isoforms. CYP3A9 mRNA levels were highest in food-deprived animals, whereas
      RU486 inhibited CYP3A9 mRNA expression and suppressed the induction effect of
      food deprivation. Food deprivation and RU486 treatment each separately caused
      increased microsomal diazepam C3-hydroxylase activity, and the combined effects
      of these treatments on this monooxygenase were additive. In contrast, the [N
      methyl-14C]erythromycin demethylase activity of the fasted, RU486-treated group
      of rats did not differ from that of the untreated group, and kinetic analyses
      revealed that both groups of animals exhibited similar Km and Vmax values. These
      results suggest that CYP3A9 may be primarily responsible for erythromycin N
      demethylation and that the isoforms induced by the combination of fasting and
      RU486 administration are CYP3A1, CYP3A23, and, to a lesser extent, CYP3A18.

PMID- 9763224
TI  - Inhibition of calcineurin by the tyrphostin class of tyrosine kinase inhibitors.
AB  - Because of their similarity to tyrosine, members of the tyrphostin family of
      tyrosine kinase inhibitors were tested as possible inhibitors of the protein
      serine/threonine phosphatase calcineurin. Calcineurin was inhibited by
      tyrphostins A8 (also designated AG10), A23 (AG18), and A48 (AG112) with p
      nitrophenyl phosphate as substrate. The IC50 values estimated with this substrate
      were 21, 62, and 30 microM for A8, A23, and A48, respectively. Two other
      tyrphostins, A46 (AG99) and A63 (AG13), did not inhibit calcineurin at
      concentrations up to 200 microM. Similar inhibition was observed with tyrphostins
      A8 and A23 using a phosphopeptide substrate (1.0 mM). Tyrphostin A8 showed
      competitive inhibition against p-nitrophenyl phosphate as the substrate, with an
      inhibition constant of 18 microM, comparable to the IC50 value. Possible chemical
      and structural features influencing inhibition are discussed based on a
      comparison of the structures of the tyrphostins tested.

PMID- 9763225
TI  - Difference in H2O2 toxicity between intact renal tubules and cultured proximal
      tubular cells.
AB  - The present study was undertaken to examine the response to H2O2 and t
      butylhydroperoxide (t-BHP) in various in vitro model systems of renal proximal
      tubules: rabbit renal cortical slices, freshly isolated rabbit proximal tubules,
      rabbit primary cultured proximal tubular cells, and opossum kidney (OK) cells. t
      BHP increased lactate dehydrogenase release and lipid peroxidation in a
      concentration-dependent manner over the concentration range of 0.2 to 3 mM in
      cortical slices, whereas H2O2 caused a similar concentration-dependent increase
      in both parameters at 5-100 mM. The sensitivity of isolated tubules to both
      peroxides was similar to that of cortical slices. In primary cultured cells and
      OK cells, however, the cytotoxicity of H2O2 was identical to that of t-BHP. The
      cytotoxicity of t-BHP was not different among all the systems examined. The
      specific activity of catalase in cortical slices was similar to that of isolated
      tubules, but it was much higher than that of primary cultured cells or opossum
      kidney cells. Glutathione (GSH) peroxidase activity was not different among all
      the systems examined. The expression of catalase mRNA in cortical slices and
      isolated tubules was higher than that in primary cultured cells, whereas those of
      superoxide dismutase, glutathione peroxidase, or beta-actin were not different
      among the systems. These results indicate that intact proximal tubules are more
      resistant to H2O2 than are cultured proximal tubular cells, and the resistance is
      due to a higher specific activity of catalase resulting from the increased
      expression of its mRNA.

PMID- 9763226
TI  - S9788 modulation of P-glycoprotein- and Multidrug-related protein-mediated
      multidrug resistance by Servier 9788 in doxorubicin-resistant MCF7 cells.
AB  - Inherent or acquired resistance to multiple natural drugs, termed multidrug
      resistance (MDR), represents a major obstacle to chemotherapy. Expression of P
      glycoprotein (P-gp) in MCF7mdr and MCF7R resistant cells was detected by reverse
      transcription-polymerase chain reaction (RT-PCR) and Western blot analysis.
      MCF7R, but not the MDR1 gene-transfected MCF7mdr cells, expressed multidrug
      related protein (MRP) concomitantly. Efficacy of an MDR modulator, designated as
      Servier 9788 (S9788), was estimated by doxorubicin (Dox) sensitization, Dox
      incorporation, and functional rhodamine 123 assay on MCF7 cell lines. Results
      showed that S9788 modulates the P-gp-associated MDR of MCF7mdr cells as well as
      the Multidrug-related protein-associated MDR of MCF7R cells.

PMID- 9763227
TI  - Differential sensitivities of recombinant human topoisomerase IIalpha and beta to
      various classes of topoisomerase II-interacting agents.
AB  - A series of topoisomerase-interacting antitumour agents were tested for their
      ability to differentially inhibit the catalytic activity of either topoisomerase
      (TOPO) IIalpha or beta, as judged by a DNA decatenation assay. The alpha form,
      relative to the beta isoform, proved 1 to 3 times more sensitive to
      nonintercalating complex-stabilizing TOPO II-interacting agents (etoposide and
      derivatives) and up to 18 times more sensitive to non-complex-stabilizing
      inhibitors of TOPO II ((+/-)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane [ICRF 159]
      and meso-2,3-bis(3,5-dioxopiperazine-1-yl)butane [ICRF 193]). However, the beta
      form of the enzyme appeared 1 to 3 times more sensitive to intercalating TOPO II
      interacting agents (daunorubicin, aclarubicin and mitoxantrone). A possible
      implication of these data are that tumours preferentially expressing either the
      alpha or the beta isoform may be differentially responsive to various classes of
      TOPO II-interacting agents.

PMID- 9763228
TI  - Co-administration of polyanions with a phosphorothioate oligodeoxynucleotide (CGP
      69846A): a role for the scavenger receptor in its in vivo disposition.
AB  - The effects of co-administering polyanions on the pharmacokinetics of a 20-mer
      phosphorothioate oligodeoxynucleotide (CGP 69846A), and the role of scavenger
      receptors in its in vivo disposition, have been investigated. Following i.v.
      administration, CGP 69846A was rapidly cleared from the plasma and distributed
      amongst high (e.g. kidney, liver, spleen), low (e.g. skeletal muscle) and
      negligible (e.g. brain) accumulating tissues. In addition it was shown that: 1)
      dextran sulphate co-administration has a dose-dependent effect on the disposition
      of CGP 69846A; 2) CGP 69846A undergoes renal filtration and renal accumulation
      largely results from tubular reabsorption; 3) cross-inhibition studies are
      consistent with CGP 69846A being recognized by scavenger receptors in vitro and
      in vivo; and 4) the scavenger receptor may be an important determinant for the in
      vivo disposition of CGP 69846A in mice. These studies contribute toward an
      increased understanding of the mechanism underlying the pharmacokinetic behaviour
      of phosphorothioate oligodeoxynucleotides.

PMID- 9763229
TI  - Selective sites for polyamine binding to rabbit intestinal brush-border
      membranes.
AB  - The intestinal polyamine transporters have not yet been identified. Our aim was
      to characterize specific polyamine binding sites in rabbit intestinal brush
      border membranes (IBBM) as a starting step for identification of polyamine
      transporters. This was investigated at 4 degrees and at low membrane
      concentration. Saturation isotherms for [3H]putrescine (PUT) binding indicated a
      single population of sites (puT) with a dissociation equilibrium constant Kd of
      3.8 microM and a density of sites Bmax of 58 pmol/mg of protein. [3H]spermidine
      (SPD) binding also involved only one class of sites (spD), albeit with a lower
      affinity (Kd = 106 microM) and higher abundance (Bmax = 1240 pmol/mg of protein)
      than puT. On the contrary, [14C]spermine (SPM) bound two classes of sites (spM1
      and spM2) differing in their affinity (Kd = 2.5 and 31.4 microM) and abundance
      (Bmax = 467 and 1617 pmol/mg of protein, respectively). Membrane association of
      SPM at 4 degrees was much faster than that of SPD and PUT, both of which
      proceeded at a similar rate. In contrast to PUT and SPD dissociation, SPM
      dissociation at 23 degrees did not follow a first-order reaction. Specifically
      bound [3H]PUT, unlike [3H]SPD and [14C]SPM, dissociated at 23 degrees
      independently of the addition of nonradioactive polyamine. Methylglyoxal-bis
      (guanylhydrazone) was an extremely potent inhibitor of PUT binding (Ki = 3.2 +/-
      1.5 nM), but as with PUT and cadaverine (CAD), it did not alter [3H]SPD and
      [14C]SPM binding substantially. The intestinal brush-border membrane may contain
      at least three sites specific for polyamine binding and exhibiting different
      ligand selectivity. Site puT might be associated with the transport system
      already described for intestinal uptake of PUT.

PMID- 9763230
TI  - Superoxide scavenging effect of Ginkgo biloba extract on serotonin-induced
      mitogenesis.
AB  - We have reported previously that serotonin (5-HT) stimulates the mitogenesis of
      bovine pulmonary artery smooth muscle cells (SMCs) through active transport of 5
      HT and cellular signaling that includes elevation of superoxide (O2.-) and
      enhancement of protein tyrosine phosphorylation. Ginkgo biloba extract 501 (EGb
      501), which has been demonstrated to act as an antioxidant, was found to block
      both the elevated O2.- and the proliferative and hypertrophic influences of 5-HT
      on SMCs, but not to directly inhibit the associated activation of NAD(P)H oxidase
      or the stimulation of phosphorylation of GTPase-activating protein (GAP). A
      similar effect of Ginkgo biloba extract 501 occurred on Chinese hamster lung
      fibroblasts (CCL-39), where 5-HT receptor, as opposed to transporter, action has
      been associated with mitogenesis. We conclude from these studies that Ginkgo
      biloba extract 501 quenches O2.- formation by 5-HT, thereby blocking its
      mitogenic effect. Stimulation of protein tyrosine phosphorylation of GAP by 5-HT
      appears to precede the elevation of O2.-.

PMID- 9763231
TI  - Generation of eicosanoids from 15(S)-hydroxyeicosatetraenoic acid in blood
      monocytes from steroid-dependent asthmatic patients.
AB  - The aim of this study was to investigate eicosanoid metabolism by human
      peripheral blood monocytes (PBM) from steroid-dependent asthmatic patients as
      compared to control subjects and untreated asthmatic patients. Eicosanoid
      biosynthesis by PBM isolated from venous blood using Percoll gradient
      centrifugation was evaluated following stimulation of 5 x 10(6) cells with
      calcium ionophore A23187, with or without exogenous 15(S)-hydroxyeicosatetraenoic
      acid (15(S)-HETE), and analyzed by reverse phase high performance liquid
      chromatography (RP-HPLC). Without 15(S)-HETE, PBM synthesized leukotriene B4
      (LTB4) only (40 +/- 12 ng and 59 +/- 11 ng for untreated and steroid-dependent
      asthmatics, respectively). In the presence of 15(S)-HETE, PBM produced six-fold
      smaller amounts of leukotriene B4 (P < 0.0001). They also released 5(S),15(S)
      dihydroxyeicosatetraenoic acid (5(S),15(S)-diHETE) in similar amounts for all the
      populations, whereas low amounts of lipoxins (LXs) were produced by PBM from
      asthmatics only (2.7 +/- 0.7 ng and 4.6 +/- 2.8 ng for untreated and steroid
      dependent asthmatics, respectively). Moreover, PBM were also able to release an
      unknown compound containing conjugated triene chromophore. Cells from steroid
      dependent asthmatic patients synthesized this unknown metabolite in higher
      amounts than controls and untreated asthmatics (133 +/- 18 ng vs 52 +/- 19 ng and
      68 +/- 15 ng, respectively, P < 0.02). This work shows for the first time that
      human PBM are able to metabolize 15(S)-HETE and lead to lipoxins and to an
      unknown metabolite, with the amounts of the latter being enhanced by long-term
      corticosteroid treatment.

PMID- 9763233
TI  - Seat pressure measurement technologies: considerations for their evaluation.
AB  - Interface pressure measurement has generated interest in the automotive industry
      as a technique which could be used in the prediction of driver discomfort for
      various car seat designs, and provide designers and manufacturers with rapid
      information early on in the design process. It is therefore essential that the
      data obtained are of the highest quality, relevant and have some quantitative
      meaning. Exploratory experimental work carried out with the commercially
      available Talley Pressure Monitor is outlined. This led to a better understanding
      of the strengths and weaknesses of this system and the re-design of the sensor
      matrix. Such evaluation, in the context of the actual experimental environment,
      is considered essential.

PMID- 9763232
TI  - Regenerative response in acute renal failure due to vitamin E deficiency and
      glutathione depletion in rats.
AB  - In this study, we investigated some factors contributing to renal regeneration
      after acute renal failure (ARF) induced by vitamin E (VE) deficiency and
      glutathione (GSH) depletion. Acute renal failure was induced by feeding rats a
      vitamin E-deficient diet for 6 weeks and then injecting buthionine sulfoximine
      (BSO), a glutathione-depleting agent. The level of hepatocyte growth factor
      (HGF), a renotropic factor for regeneration in the kidney, showed a transient
      increase at 5 hr after the BSO treatment. Subsequently, renal ornithine
      decarboxylase (ODC) activity, a marker of G1 phase, and labeling index (LI) of
      proliferating cell nuclear antigen (PCNA), a marker of DNA synthesis (S phase),
      reached peaks at 10 and 53 hr after the injection, respectively. Thus, it appears
      that the increase in ornithine decarboxylase activity and subsequent elevation in
      proliferating cell nuclear antigen labeling index following the increase in the
      hepatocyte growth factor level in the kidneys are closely related to the renal
      regenerative response after acute renal failure.

PMID- 9763234
TI  - Guidelines for force-travel combinations of push button switches for older
      populations.
AB  - Current demographic trends indicating that older persons will comprise an
      increasingly larger proportion of our population points to the need for paying
      closer attention to age-related disabilities in designing products and
      environments capable of accommodating this population. This study addresses the
      development of design guidelines for push-button switches associated with a
      variety of consumer products commonly used by older persons. Three groups, each
      consisting of 12 male and female subjects, participated in the study, with all
      subjects over the age of 50 and the average age being 70 years. The groups were
      categorized on the basis of whether subjects were able-bodied, had arthritis
      affecting their hands or fingers, or had hand tremor; these categories were
      validated through the use of functional assessment tools. A scheme was developed
      to categorize commercially available switches based on force-travel combinations,
      and an experiment was conducted to assess the subject's ability to momentarily
      and continuously operate the switches, as well as to derive the subjective
      preferences for these switches. Based on observations from behavioral strategies,
      and graphical and statistical analysis of preferences, a set of design guidelines
      was proposed to enable consumer product designers and manufacturers to better
      accommodate the needs of both able-bodied and functionally impaired older adults.

PMID- 9763235
TI  - Connotation of hazard for signal words and their associated panels.
AB  - The present study examined the ability of signal words (e.g. DANGER) and their
      associated panels to convey hazard-level information, both individually and
      redundantly. Subjects constructed signs on a computer for 30 different scenarios.
      The use of signal words and panels was observed as a function of the level of
      hazard associated with the scenario. The results show that (a) the connoted level
      of hazard for signal words is not perceived as most standards suggest, (b)
      certain panel components (e.g. colour and symbols) are most critical in conveying
      hazard-level information, (c) no current set of standards or recommendations
      specifies panel formats which use these panel components optimally, and (d) the
      use of signal word panels was not necessarily based on the choice of signal word
      or on the level of hazard for the particular scenario. The results suggest the
      need for a re-evaluation of current signal word hierarchies.

PMID- 9763236
TI  - Torque resistance of the passive tissues of the trunk at axial rotation.
AB  - Sitting in a twisted working posture is common when driving an agricultural
      tractor in the field. To be able to twist backwards, the driver has to overcome
      the torque from the passive tissues (passive resistance). The purpose of this
      investigation was to determine the relationship between passive resistance at
      axial rotation and twisting angle of the trunk when a person is seated. Ten
      healthy tractor drivers and 10 healthy office workers were passively twisted
      about the cranio-sacral axis with simultaneous measurements of the torque needed
      to twist them and the twisting angle. Surface electromyogram was used to control
      the relaxation of the muscles of the subjects. An exponential function was fitted
      to the data, which shows that passive resistance increases progressively with
      twisting angle. No significant differences in trunk passive resistance due to the
      subject's occupation, direction of twist or their interactions could be found.
      The fitted function is useful when assessing the load in the trunk in tractor
      driving, but also for other occupational activities where the trunk is twisted.

PMID- 9763237
TI  - Musculoskeletal disorders among dentists and variation in dental work.
AB  - The purpose was to assess risk factors in dentistry which may contribute to
      musculoskeletal disorders. A questionnaire was used to identify common work
      tasks, and to estimate one year prevalence for troubles (65% for the
      neck/shoulder, 59% for the low back). In a field study working postures and
      electromyography (shoulder/neck) were registered during the three most common
      work tasks. Prolonged neck flexion and upper arm abduction were found, as well as
      high static muscle activity levels (splenius and trapezius muscles). No
      differences between work tasks were found regarding postures, frequencies of
      movements or muscle activity. Alterations between the three work tasks do not
      produce sufficient variation to reduce musculoskeletal load on the neck and
      shoulders.

PMID- 9763238
TI  - The role of 'know-how' in maintenance activities and reliability in a high-risk
      process control plant.
AB  - Using observation of a maintenance operator's activity and 'the history' that it
      produced as a basis, we will discuss the role of 'know-how' in maintenance
      activities, and particularly the problems raised by putting this knowledge into
      words. Second, we will underline the contribution of this know-how to the
      operational reliability of the facilities and we will investigate its being taken
      into account in work instructions. With such issues as a basis, we will conclude
      with the need for ergonomists to develop modes of interviewing to help people to
      put know-how into words, so that it is recognized and considered in maintenance
      activity organization.

PMID- 9763239
TI  - Human factors in technology replacement: a case study in interface design for a
      public transport monitoring system.
AB  - This paper describes ergonomic issues raised during a project to provide a
      replacement real-time bus route control system to a large public transport
      company. Task and system analyses highlighted several deficiencies in the
      original system architecture, the human-machine interfaces and the general
      approach to system management. The eventual live prototype replaced the existing
      original system for a trial evaluation period of several weeks. During this
      period a number of studies was conducted with the system users in order to
      measure any improvements the new system, with its ergonomic features, produced
      over the old. Importantly, the results confirmed that (a) general responsiveness
      and service quality were improved, and (b) users were more comfortable with the
      new design. We conclude with a number of caveats which we believe will be useful
      to any group addressing technology impact in a large organisation.

PMID- 9763240
TI  - An ergonomic approach to public squatting-type toilet design.
AB  - This paper reports a case study on public squatting-type toilet design, which was
      undertaken with a special emphasis on ergonomic considerations. A field survey on
      the use of public toilets in Taipei reveals that almost half of the subjects take
      a non-sitting posture while using the sitting-type public toilets and 86% of the
      subjects agreed that the squatting-type public toilets better satisfy sanitary
      requirements. An experiment was conducted to determine relevant anthropometric
      data for a redesign of squatting-type toilets. One of the variables studied was
      the effect of the footstep slope on squatting comfort. A total of 80 subjects as
      tested on four footstep slopes: 0 degrees, 15 degrees, 30 degrees and 45 degrees.
      Their heart rates were measured before and after the test, and their subjective
      evaluations of squatting comfort were also recorded. The 15 degrees slope was
      found to be preferred. These findings were then used in design development where
      mock-ups were presented to subjects for evaluation, then modifications were made
      and further tests conducted for verification. The result shows that the ergonomic
      approach is feasible recommended to be adopted in the process of product design
      of such facilities.

PMID- 9763241
TI  - Developmental toxicity of metal chelating agents.
AB  - Chelation therapy is the basis for the treatment of metal poisoning. A number of
      chelating agents have been widely used since the 1950s. Since these agents can be
      potentially given to a metal-intoxicated pregnant woman, their intrinsic
      developmental toxicities are a matter of concern. While the embryo/fetal toxic
      effects of some chelators have been reported to occur at doses higher than those
      currently given in the medical treatment of metal poisoning, according to
      experimental data the potential use of other metal antidotes is controversial. In
      those cases, the benefits and risks of usage should be carefully weighed. The
      developmental toxicity of known chelators of clinical interest is presented here.
      Chelating agents were divided according to the following structurally related
      categories: polyaminocarboxylic acids, chelators with vicinal -SH groups, beta
      mercapto-alpha-aminoacids, hydroxamic acids, ortho-hydroxycarboxylic acids, and
      miscellaneous agents. Since it has been demonstrated that the teratogenic
      potential of most chelators is, at least in part, due to induced trace element
      deficiencies, the advisability of mineral supplements during chelation treatment
      is also discussed.

PMID- 9763242
TI  - Is benzodiazepine use during pregnancy really teratogenic?
AB  - Benzodiazepines (BDs) have a widespread use among people suffering from anxiety.
      These drugs easily cross the placenta and may affect the developing embryo and
      fetus. The literature is divided as to whether BD may cause an increase in
      spontaneous abortions or congenital anomalies. From the years 1988 to 1996, 756
      women called the Israeli TIS concerning exposures to BD prior to or during
      pregnancy. Of 599 women who called us during pregnancy, we have follow-up
      information on 460 pregnancies (76.6%). The incidence of congenital anomalies
      (3.1%) was not different from that found in 424 control pregnancies (2.6%). There
      was a significantly higher incidence of induced abortions (14.1% vs. 4.7%, P =
      0.00) and of spontaneous abortions (8.7% vs. 5.2%, P = 0.01). From an examination
      of our results, it does not appear that BD during pregnancy caused an increase in
      the incidence of birth defects. There was no specific defect in the offspring.
      The increase in the rate of induced abortions is probably related to the
      counseling of the callers, and the increase in spontaneous abortions seems to be
      a result of the lower gestational age at the time of counseling in the women
      exposed to BD. It is unknown whether BD could be responsible for developmental or
      behavioral problems, which are observed only at a later stage.

PMID- 9763243
TI  - Transplacental pharmacokinetics of cocaine and benzoylecgonine in plasma and hair
      of rhesus monkeys.
AB  - There is large variability in the rate and extent of fetal damage from cocaine in
      humans; however, the sources of such variability are not presently known. In
      order to study the relationship between maternal cocaine pharmacokinetics at the
      end of pregnancy and maternal or infant cocaine and benzoylecgonine hair
      concentrations at birth, ten rhesus monkeys were administered cocaine
      intramuscularly throughout pregnancy. Cocaine and benzoylecgonine hair
      concentrations were determined at birth and correlated with maternal
      pharmacokinetics during pregnancy. There were no correlations between either
      maternal cocaine Cmax or AUC0-infinity and maternal and infant hair cocaine or
      benzoylecgonine concentrations. There were no significant correlations between
      maternal hair benzoylecgonine concentrations and either maternal benzoylecgonine
      AUC0-120 (r = 0.60; P = 0.07) or benzoylecgonine Cmax (r = 0.60; P = 0.07). No
      correlations existed between infant hair benzoylecgonine concentrations and
      either maternal benzoylecgonine AUC0-120 (r = 0.30; P = 0.40) or benzoylecgonine
      Cmax (r = 0.30; P = 0.40). Also, no correlation was found between maternal
      cocaine dose and maternal or infant cocaine and benzoylecgonine hair
      concentrations. In comparison to toxicants such as nicotine and carbon monoxide
      for which there is a good correlation between maternal systemic exposure and
      neonatal concentrations, the lack of a similar relationship for cocaine is
      consistent with the role of the placenta in contributing to the variability in
      the amounts of cocaine reaching the fetus and hence, potentially to the risk of
      adverse fetal outcome.

PMID- 9763245
TI  - The effect of zinc supplementation on the effects of lead on the rat testis.
AB  - With increasing concerns about environmental pollution, the interaction of
      micronutrients with toxic metals is of great interest. The present study was
      designed to investigate testicular effects of lead following concomitant
      administration of zinc. Lead was administered orally as lead acetate (50 mg/kg
      b.w.) daily for 3 months to male Portan rats with or without zinc (1 mg/kg b.w.
      as zinc sulphate). The control group was given the same volume of distilled
      water. Endpoints included lead concentration in various body organs as well as in
      the reproductive system, including testicular subfractions; the testicular
      enzymes superoxide dismutase (SOD) and catalase; the marker enzyme delta
      aminolevulinic acid dehydratase (delta-ALAD); and testicular histoarchitecture.
      The concentrations of lead in bone, kidney, prostate, testis, liver, epididymis,
      spleen, seminal vesicles, and blood were significantly higher in lead-treated
      rats. Lead deposition was reduced in animals that received supplemental zinc.
      There was a 30% reduction in lead deposition in the testis when zinc was
      coadministered. At the subcellular level, there was differential accumulation of
      lead; the nucleus preferentially took up the metal after lead treatment alone,
      while zinc coadministration shifted lead accumulation to the mitochondria. A
      significant decrease in delta-ALAD and in SOD activity was seen in the testis
      with lead treatment. Coadministration of zinc prevented these decreases, at least
      partially. Zinc coadministration did not prevent the inhibition of catalase
      observed with lead treatment. Histologically, the alterations in the testis with
      lead treatment alone were more pronounced compared to animals in which zinc was
      supplemented. Improvement in the inhibition of delta-ALAD and in the ubiquitous
      cellular enzyme SOD suggests less testicular tissue damage due to detoxification
      of free radicals. In conclusion, zinc supplementation ameliorates lead-induced
      testicular damage both at the cellular and subcellular level. The protective
      effect may be due to differential distribution of lead, either because of
      competition between lead and zinc or displacement of lead by zinc.

PMID- 9763244
TI  - Dysmorphogenic effects of a specific protein kinase C inhibitor during
      neurulation.
AB  - Protein kinase C (PKC) plays a key role in signal transduction and is an
      important mediator of events throughout development. However, no information
      exists regarding the effect of a specific PKC inhibitor on mammalian
      embryogenesis during neurulation. This investigation was undertaken to examine
      the effects of a specific inhibitor of PKC, as well as inhibitors of other
      important kinases, on cultured mouse embryos. CD-1 mouse embryos (3 to 6 somite
      stage) were exposed to bisindolylmaleimide I (a specific PKC inhibitor) as well
      as specific inhibitors of PKA, PKG, and MAP kinase kinase for 24 h. The PKC
      inhibitor was a potent embryotoxicant and elicited malformations at
      concentrations as low as 0.01 microM. Inhibitors of other kinases also produced
      malformations but at much higher concentrations than those required to produce
      similar defects with the PKC inhibitor. These data suggest that PKC plays an
      important role in mammalian neurulation. Further research is required to clarify
      the mechanism by which PKC inhibition at this developmental stage produces
      malformations and the potential effects of environmental toxicants with PKC
      inhibitory properties on this signal transduction pathway.

PMID- 9763246
TI  - Behavior and reproductive function of rat male offspring treated prenatally with
      5-bromo-2'-deoxyuridine.
AB  - 5-Bromo-2'-deoxyuridine (BrdU) was administered intraperitoneally to Sprague
      Dawley rats at doses of 50 mg/kg/d on Days 9 through 15 and at 100 mg/kg/d on
      Days 16 through 20 of gestation. Dams were allowed to deliver naturally. Male
      offspring were subjected to a variety of pre- and postweaning behavioral tests:
      surface righting, negative geotaxis, open field test, Biel maze test, wheel cage
      test, and shuttlebox avoidance test. After puberty, masculine sexual behavior was
      observed. Male offspring of dams treated with BrdU on Days 9 through 15 of
      gestation showed an accelerated negative geotaxis reflex and increased ambulation
      and rearing in open field, while those of dams treated on Days 16 through 20 of
      gestation showed normal activity. Offspring of dams treated on Days 9 through 15
      of gestation showed a higher activity level in the wheel cage than offspring of
      dams treated on Days 16 through 20 of gestation. In the Biel maze, offspring of
      dams treated on Days 9 through 15 of gestation showed impaired learning and
      memory. In the shuttlebox avoidance response, offspring of dams treated on Days 9
      through 15 of gestation moved significantly more than offspring of dams treated
      on Days 16 through 20 of gestation. Masculine sexual behavior was markedly
      reduced in male offspring of dams treated on Days 9 through 15 of gestation.
      However, no significant differences between groups in blood pressure nor heart
      rate were noted. We conclude that male offspring of dams treated with BrdU on
      Days 9 through 15 of gestation are hyperactive without hypertension and that
      these offspring show an impairment of masculine sexual behavior, i.e.,
      hyposexuality.

PMID- 9763247
TI  - Influence of organochlorine pesticides on transmembrane potential, oxidative
      activity, and ATP-induced calcium release in cultured bovine oviductal cells.
AB  - The present study investigated the effects of the pesticides DDT, MXC, and
      gammaHCH on transmembrane potential, oxidative activity, cytotoxicity and ATP
      induced intracellular Ca2+ release in cultured bovine oviductal cells.
      Transmembrane potential, oxidative activity, and cytotoxicity were assessed using
      the fluorescent dyes bis-oxonol, dihydrorhodamine 123, and propidium iodide (PI),
      respectively, and measured spectrofluorometrically in a microplate reader. The
      cultured cells were loaded with Ca2+-sensitive fluorochrome fura-2-AM, and
      cytosolic free calcium ([Ca2+]i) was monitored by a microscope image analysis
      system. A dose-dependent increase in depolarization and changes of oxidative
      activity were observed over a concentration range of 8 to 128 microM DDT and MXC
      compared to nonexposed controls. At a concentration of 16 microM DDT or MXC, the
      oxidative activity and depolarization of cells were significantly enhanced
      compared to controls, but most of the cells were intact as indicated by the fact
      that PI-staining was not significantly increased. Trypan-blue staining indicated
      that the viability of oviductal cells decreased significantly when exposed to
      concentrations of 64 and 128 microM DDT or MXC. ATP-mediated enhancement of
      [Ca2+]i in cells was almost completely inhibited after incubation with 128 microM
      DDT for 3 h at 37 degrees C. This response was reduced to approximately 50% after
      incubation of the cells with MXC at 128 microM; lindane did not significantly
      interfere with the above physiologic parameters.

PMID- 9763248
TI  - Influence of organochlorine pesticides on maturation and postfertilization
      development of bovine oocytes in vitro.
AB  - The aim of this study was to perform a dose-response test to determine whether
      bovine oocytes exposed to dichlorodiphenyltrichloroethane (DDT),
      hexachlorocyclohexane (gammaHCH), or methoxychlor (MXC) in vitro would exhibit
      changes in maturation rates, cleavage rates at Day 2, or blastocyst rates at Day
      7 to 8 after fertilization in vitro (IVF). All three pesticides affected
      maturation and degeneration rates in a dose-dependent manner, but to different
      extents. Higher concentrations of pesticides were associated with higher rates of
      chromatin degeneration. Because the maturation of bovine oocytes was depressed in
      a dose-dependent manner, the fertilizability and further embryonic development of
      in vitro matured oocytes was studied at the lowest previously tested
      concentration (7.25 microg/mL) only. No significant difference in fertilization
      rates was seen between unexposed control and treated groups. The cleavage rates
      did not differ among groups 48 h after IVF. The number of morulae and blastocysts
      on Day 7 to 8 after IVF, which is commonly used as a parameter for normal
      development, was significantly different between control and DDT- and gammaHCH
      treated groups, but not between the control and MXC groups. The pesticides did
      not differ significantly among themselves. These results show that the tested
      pesticides decrease the rate of normal oocyte maturation in vitro in a dose
      dependent manner. The effect of the lowest concentration of pesticides is seen
      only after Day 7 of embryo development.

PMID- 9763249
TI  - Arterial reconstruction in the ischemic hand and wrist: effects on microvascular
      physiology and health-related quality of life.
AB  - Patients were evaluated before and after arterial reconstruction surgery (1) to
      define the physiology of the digital microcirculation in chronic subcritical
      ischemia, (2) to demonstrate the short-term effects of successful arterial
      reconstruction on microvascular flow, and (3) to document the effects of surgery
      on symptoms, function, and health-related quality of life. Arterial insufficiency
      was the result of a proximal reconstructible occlusive lesion, 1 or more distal
      unreconstructible occlusions, and secondary reactive vasospasm. Microvascular
      physiology was evaluated by monitoring digital temperatures, microvascular
      perfusion (laser Doppler fluxmetry) and perfusion patterns (laser Doppler
      perfusion patterns (laser Doppler perfusion imaging). Following successful
      vascular reconstruction, digital temperatures and microvascular perfusion
      improved significantly, approaching control levels. Although cold sensitivity was
      unchanged, symptoms decreased and upper extremity function and health-related
      quality of life improved after successful proximal reconstruction in patients
      with 2-level arterial occlusion.

PMID- 9763250
TI  - Major replantation versus revision amputation and prosthetic fitting in the upper
      extremity: a late functional outcomes study.
AB  - The functional outcomes of amputated arms that were either replanted or had a
      prosthesis were compared. In addition, factors that influenced the functional
      outcome of replants were evaluated. The Carroll test was used to evaluate
      functional capacity of 22 successful upper extremity replantations at or proximal
      to the wrist as well as 22 amputees (at similar levels) fitted with a variety of
      prosthetic devices. The outcome was excellent or good in 8 (36%) replanted limbs.
      This proportion was statistically higher than those grades in the prosthetic
      group. When the groups were more closely matched (adults with below elbow
      injuries), the replantation group had 6 (50%) good or excellent outcomes and the
      prosthetic group had none. An analysis of covariance of the replantations
      demonstrated a statistical association between a better outcome in younger
      patients with more distal injuries. This study indicates that replantation
      produces superior functional results compared with amputation and a prosthesis.

PMID- 9763252
TI  - Vascular anatomy of the ulna.
AB  - The vascular anatomy of the ulna was studied. Ten fresh-frozen upper extremity
      specimens were injected with India ink and latex solution. The extraosseous
      anatomy was dissected. The intraosseous anatomy was evaluated after treatment
      with the modified Spalteholtz technique. The proximal periarticular portion of
      the ulna was supplied by numerous, very small periarticular branches running in
      the capsule. A major intramedullary nutrient vessel arose from the ulnar artery
      or ulnar recurrent artery in all specimens and entered at the base of the
      coronoid. The ulnar artery gave off a common interosseous artery that branches
      into posterior and anterior interosseous vessels that course distally on the
      interosseous membrane. The interosseous vessels were critical for they supply the
      only observed vascular branches to the ulna diaphysis. The anterior interosseous
      vessel supplied on average 7 branches (range, 3-11 branches) to the ulna
      diaphysis spaced at generally regular 2-cm intervals, with the number of branches
      decreasing in the distal third. The posterior interosseous artery supplied an
      average of 11 branches (range, 9-14 branches) to the ulna diaphysis spaced at 1
      cm intervals. The distal ulna metaphysis was supplied by terminal branches of the
      anterior interosseous artery. The ulnar head was supplied by small branches off
      the ulnar artery proper. In summary, the blood supply to the ulna diaphysis was
      dependent on segmental vessels provided by the anterior and posterior
      interosseous vessels. No dominant intramedullary vessel was observed in the
      diaphysis. The interosseous vessels should be protected when treating a ulna
      fracture or a nonunion, or when performing an osteotomy.

PMID- 9763251
TI  - The effect of transdermal nicotine on digital perfusion in reformed habitual
      smokers.
AB  - The effects of transdermal nicotine-assisted smoking cessation on digital
      perfusion and health-related quality of life were assessed in 10 chronic smokers.
      Components of digital blood flow were evaluated by digital temperature and laser
      Doppler fluxmetry before, during, and after a standardized cold challenge.
      Nutritional flow was measured by vital capillaroscopy; a quantitative perfusion
      profile was obtained by laser Doppler perfusion imaging. A battery of validated
      measures were used to evaluate health-related quality of life. The microvascular
      response of smokers was evaluated before smoking cessation and at 2 and 7 days
      after smoking cessation and was compared with the response of nonsmoking
      controls. Results demonstrated that a (1) cutaneous microvascular perfusion was
      lower in smokers than nonsmokers, (2) the acute administration of transdermal
      nicotine did not decrease cutaneous perfusion, (3) smoking cessation and
      transdermal nicotine normalized digital microvascular perfusion by 7 days, and
      (4) transdermal nicotine and smoking cessation did not negatively impact health
      related quality of life.

PMID- 9763253
TI  - The histologic anatomy of the volar plate.
AB  - The volar plate (VP) is critical to the stability of the proximal interphalangeal
      joint. This study clarifies the macro- and micro-architectural structure of the
      VP and correlates these findings with its functional properties. Microscopic
      evaluation of cadaver specimens revealed a trilaminar structure of the VP with
      differential orientation and organization of collagen fibers in the volar,
      central core, and dorsal check rein sections of the plate. This description
      differs from the existing literature and adds to the understanding of the
      functional properties of the VP. The most important finding is a dense "basket
      weave" of collagen fibers oriented in 2 perpendicular planes within the central
      core of the VP. This orientation may contribute primarily to the resistance of
      the VP to both longitudinal and torsional stress. This study adds to the
      understanding of the histologic basis for the function of the VP and the
      mechanisms involved in its injury.

PMID- 9763254
TI  - Palmar fracture dislocation of the proximal interphalangeal joint.
AB  - Palmar fracture dislocation of the proximal interphalangeal joint is uncommon.
      Thirteen patients treated for this injury were retrospectively reviewed. There
      were 9 acute injuries. Seven were treated by closed reduction and percutaneous
      pin fixation and 2 were treated by open reduction and internal fixation. The 4
      chronic injuries (more than 1 month after injury) were treated with open
      reduction and soft tissue reconstruction. The length of follow-up averaged 55
      months. Eight patients were free from pain. Postoperative proximal
      interphalangeal motion averaged 91 for the acute injuries and 70 degrees for the
      chronic injuries. Follow-up radiographic findings were notable for an increased
      height of the middle phalangeal base in 6 patients, articular irregularity in 4,
      and residual subluxation in 2; however, these changes did not correlate with the
      clinical results. Complications included loss of reduction in 1 patient,
      progressive swan neck deformity in 1, and development of an average 25 degrees
      extension lag of the distal interphalangeal joint in 5.

PMID- 9763255
TI  - In situ osteotomy for extra-articular malunion of the proximal phalanx.
AB  - Eleven patients had correction of extra-articular malunions of the proximal
      phalanx by in situ osteotomy stabilized with a dorsal plate, which healed within
      7 weeks. The patients' average age was 27 years; 8 of the patients were male.
      After an average follow-up period of 35 months (range, 25-54 months), all the
      patients had correction of the overlapping or scissoring of the digits during
      flexion. The rotation deformity improved from 17 degrees to 2 degrees and the
      angular deformity present in 6 patients improved from 14 degrees to 0 degrees.
      None of the patients lost motion. On average, the patients improved from 85
      degrees to 100 degrees flexion for the proximal interphalangeal joint and from 45
      degrees to 55 degrees for the distal interphalangeal joint.

PMID- 9763256
TI  - Complications and range of motion following plate fixation of metacarpal and
      phalangeal fractures.
AB  - Eighty-two patients with 105 metacarpal and/or phalangeal fractures stabilized
      with plates were retrospectively reviewed to assess complications and outcomes.
      Despite stable fixation and early mobilization, major complications were
      encountered in 36% of fractures, especially with phalangeal and open fractures.
      Complications included stiffness, nonunion, plate prominence, infection, and
      tendon rupture. Forty-eight of 63 (76%) metacarpal fractures and 44 of 66 (67%)
      closed fractures had a final range of motion greater than 220 degrees; however,
      only 4 of 37 (11%) phalangeal fractures and 8 of 34 (24%) open fractures achieved
      this outcome. Despite technical advances in plate design and instrumentation,
      including lower-profile titanium plates, complications occur commonly with
      metacarpal and phalangeal fractures, leading to a high incidence of
      unsatisfactory results. We do not condemn plate fixation, and attribute many of
      our unsatisfactory results to the frequent use of plates in open and phalangeal
      fractures.

PMID- 9763257
TI  - The Stener lesion revisited: a case report.
AB  - Proximal displacement of a ruptured ulnar collateral ligament of the
      metacarpophalangeal joint of a thumb (Stener lesion) can result in chronic
      instability if left untreated. Rupture without displacement generally leads to
      complete recovery. An associated fracture can give information about the position
      of the ruptured ligament. However, 2 cases are presented demonstrating that
      displacement of the ligament can occur in the absence of displacement of the bony
      fragment. This suggests that physical examination is required to determine
      stability with injuries to the ulnar structures of the thumb metacarpophalangeal
      joint.

PMID- 9763258
TI  - Isolated closed rupture of the bony insertion of the flexor digitorum
      superficialis tendon: an unusual case.
AB  - We describe a case of isolated rupture of the flexor digitorum superficialis
      tendon due to middle phalangeal cortical bone avulsion with a 4-month delay in
      treatment. X-ray examination revealed an area of calcification in the flexor
      tendon sheath proximal to the proximal interphalangeal joint. Excision of the
      bone fragment and surrounding scar tissue corrected nearly all the 60 degrees
      extension lag at the proximal interphalangeal joint, which was the most notable
      functional loss.

PMID- 9763259
TI  - Limited surgical treatment of de Quervain's disease: decompression of only the
      extensor pollicis brevis subcompartment.
AB  - A septum between the abductor pollicis longus tendon and the extensor pollicis
      brevis (EPB) tendon in the first extensor compartment is frequently encountered
      during surgical treatment of de Quervain's disease. It was hypothesized that de
      Quervain's disease was secondary to EPB entrapment and the decision was made to
      decompress only the EPB subcompartment. Twenty-two patients were treated with
      this method. Sixteen patients had a septum in the first extensor compartment and
      6 patients had a single canal. After surgery, all patients had complete relief of
      pain and tenderness over the first extensor compartment. The results of
      Finkelstein's test were negative in all cases. We conclude that de Quervain's
      disease is secondary to EPB entrapment. In those cases with a septum, it is
      sufficient to decompress only the EPB subcompartment.

PMID- 9763260
TI  - Motor collateral sprouting through an end-to-side nerve repair.
AB  - The outcome of end-to-side repair of peripheral nerves was investigated. The
      sciatic nerve in 10 male Sprague-Dawley rats was dissected to its tibioperoneal
      junction. The nerve to the medial gastrocnemius muscle, branching from the tibial
      nerve, was ligated at its origin and divided. Its distal end was sutured to an
      epineurial window on the side of the intact tibial nerve 1 cm distally. At 12
      weeks, physiologic evaluation of the medial gastrocnemius muscle and analyses of
      histologic preparations of nerve and muscle were performed. The results showed
      that reinnervation successfully occurred in 8 rat media gastrocnemii. The mean
      weight of the reinnervated medial gastrocnemius was 73% of the contralateral
      normal muscle, the mean muscle fiber cross-sectional area of the reinnervated
      muscle was 72%, and the force of contraction was 60%. Analyses of histologic
      preparations revealed evidence of myelinated axons in the medial gastrocnemius
      nerve and no evidence of damage to axons of the donor tibial nerve.

PMID- 9763261
TI  - The anatomy of the recurrent branch of the median nerve.
AB  - One hundred one fresh-frozen cadavers were dissected under loupe magnification to
      spatially define the origin of the recurrent branch of the median nerve and to
      define its course with respect to the distal edge of the transverse carpal
      ligament (TCL). The spatial orientation, number, and course of the recurrent
      branch was carefully determined. Calipers were used to measure the distance
      between the recurrent branch and the TCL. Histologic analysis of the fascia
      surrounding the recurrent nerve was performed. The recurrent branch of the median
      nerve was classified into 3 types. Type I passed through the TCL; it is rare,
      occurring in 7% of the specimens. Type II nerves (74%) passed distal to the TCL
      through separate obliquely oriented fascia that originated on the TCL and
      inserted on the undersurface of the palmar aponeurosis. Type 111 (19%) passed
      distal to the TCL, but did not pass through the obliquely oriented fascia. The
      distance from the distal edge of the TCL was significantly different between the
      3 types. Ninety-nine percent of recurrent branches originated either from the
      central portion of the median nerve or just radial to it. There were no ulnar
      origins. Four cadavers (4%) had more than 1 recurrent branch. The variability in
      the literature on the anatomy of the recurrent branch can be accounted for by
      failure to properly identify the TCL as being separate from the obliquely
      oriented fascia distal to the TCL through which the nerve frequently penetrates.
      Histologic analysis confirmed a difference between the TCL and these oblique
      fibers that can surround the recurrent nerve. This study concludes that the
      transligamentous branch (type I) is uncommon and the reported high incidence of
      branches passing through the TCL can be explained by mistakenly combining
      recurrent nerve types I and II.

PMID- 9763262
TI  - Differential latency testing: a more sensitive test for radial tunnel syndrome.
AB  - A modification of the standard electrodiagnostic test was developed in an effort
      to provide a more sensitive electrodiagnostic evaluation in radial tunnel
      syndrome. Radial motor nerve latency recordings were obtained in 3 different
      forearm positions: neutral, passive supination, and passive pronation. The
      maximal difference in these recordings, the differential latency, in 25 patients
      with radial tunnel syndrome of greater than 6 months duration (test group) was
      compared with those in 25 asymptomatic volunteers (control group). Differential
      latency recordings were obtained in all patients in the test group before and
      after surgery. Radial nerves that were compressed demonstrated a significantly
      greater differential latency (0.44+/-0.12 ms) versus controls (0.12+/-0.008 ms).
      Following radial nerve decompression, differential motor latencies in the test
      group decreased below control values, demonstrating a resolution of the provoked
      electrical response with a postoperative differential latency of 0.07+/-0.05 ms.
      Our results demonstrate the differential motor latency of the radial nerve to be
      a sensitive electrodiagnostic tool in patients with radial tunnel syndrome. A
      differential latency of > or =0.30 ms was considered indicative of radial tunnel
      syndrome.

PMID- 9763263
TI  - The results of revision carpal tunnel release following previous open versus
      endoscopic surgery.
AB  - This study compared the outcomes of revision open carpal tunnel release following
      previous open versus endoscopic release to determine whether revision surgery has
      different results based on the type of initial surgical treatment. Thirty
      revision carpal tunnel releases were performed in 13 wrists that had previous
      endoscopic release and in 17 wrists with prior open release. At a follow-up visit
      an average of 30 months after surgery, self-assessment questionnaires
      demonstrated improved or complete symptom relief in 77% of the postendoscopic
      release group versus 47% in the previous open release group. Combining both
      groups, 18% of workers' compensation patients improved after revision surgery
      compared with 84% of those with conventional insurance (p < .05). Patients having
      persistent or recurrent symptoms following a previous endoscopic carpal tunnel
      release have a greater chance of symptom improvement or resolution compared with
      patients who had previous open carpal tunnel surgery. Our results support the
      observation that a higher incidence of incomplete release of the carpal tunnel is
      found with endoscopic surgery than with open release.

PMID- 9763264
TI  - Distance between the median nerve and ulnar neurovascular bundle: clinical
      significance with ultrasonographically assisted carpal tunnel release.
AB  - In ultrasonographically assisted carpal tunnel release, the zone of the
      transverse carpal ligament between the median nerve and ulnar neurovascular
      bundle is of significance because proximity of the cutting device to these
      structures depends on its width. In this study, we measured the width of the zone
      at 5 levels in 60 wrists from 54 patients with surgery-indicated idiopathic
      carpal tunnel syndrome. The width of the 5 levels ranged from 2.8 to 11.2 mm
      (mean, 7.1 mm) at the hook of the hamate, 3.0 to 12.5 mm (mean, 7.9 mm) at the
      distal one fourth of the carpal tunnel, 2.8 to 12.4 mm (mean, 8.0 mm) at the
      midsection of the tunnel, 1.5 to 13.0 mm (mean, 7.4 mm) at the proximal one
      fourth of the tunnel, and 5.3 to 17.2 mm (mean, 10.2 mm) at the wrist crease.
      These widths were not significantly correlated with radiographic measurements of
      the hand (cord of the radiocarpal joint arc, carpal height, third metacarpal, and
      hand length). We conclude that there is considerable variation of the width among
      individuals. Based on our clinical experience (3 wrists of 3 patients in this
      study), patients with a width of < or =3 mm at any level should be screened out
      preoperatively by wrist imaging. Our findings also may be of use to surgeons
      performing endoscopic carpal tunnel release.

PMID- 9763265
TI  - Malignant melanoma extending along the ulnar, median, and musculocutaneous
      nerves: a case report.
AB  - We analyzed a case of malignant melanoma that resembled malignant peripheral
      nerve sheath tumor with marked neurotropism. The subungual tumor in the right
      ring finger extended along the ulnar nerve for a distance of 30 cm, as well as
      along the median and musculocutaneous nerves, with lymph nodal metastases. The
      tumor consisted of interlacing spindle-shaped cells with large nuclei and
      distinct nucleolei. Immunohistochemically, the tumor cells were diffusely
      positive for S-100 protein. Five years after forequarter amputation, the patient
      is alive without disease. Malignant melanoma has the potential of invading
      several major peripheral nerves and must be distinguished from malignant
      peripheral nerve sheath tumor, which rarely metastasizes to regional lymph nodes.

PMID- 9763266
TI  - First metacarpal subsidence during pinch after ligament reconstruction and tendon
      interposition basal joint arthroplasty of the thumb.
AB  - Trapeziectomy, ligament reconstruction and tendon interposition arthroplasty is
      one of the most commonly performed procedures to address pain and instability due
      to osteoarthritis at the basal joint of the thumb. To determine the effect of
      stress on first metacarpal subsidence, 15 ligament reconstruction and tendon
      interposition basal joint arthroplasties were evaluated after a mean follow-up of
      32 months. Radiographs were obtained of the arthroplasty at rest and then with
      maximal effort key pinch stress, which is known to subject the first
      carpometacarpal joint to considerable axial compression stress. Compared with the
      preoperative x-rays, the first metacarpal had subsided 21% of the arthroplasty
      space at rest. Under stress, the first metacarpal was found to subside another
      10.5% in height. No subluxation of the metacarpal base could be detected. Key
      pinch strength improved 17% from the preoperative strength. Tip-to-tip pinch
      strength improved 17% from the preoperative measurement. Grip strength improved
      17% from the preoperative measurement. Grip strength was 9% greater than the
      preoperative grip strength. There was no statistical association between the
      amount of first metacarpal subsidence and follow-up key pinch, tip pinch, or grip
      strength. With axial compressive loading of the arthroplasty, such as in lateral
      pinch, there is some further proximal migration of the first metacarpal, but this
      is minimal and does not correlate with functional outcome.

PMID- 9763267
TI  - Reconstruction of the scapholunate ligament in a cadaver model using a bone
      ligament-bone autograft from the foot.
AB  - This study is an investigation of a new procedure in which the scapholunate
      interosseous ligament (SLIL) is reconstructed using a bone-ligament-bone
      autograft from the foot. After investigation, the dorsal medial portion of the
      navicular-first cuneiform ligament (NFCL) was chosen for testing as a potential
      donor since it is similar in length and thickness to the SLIL and it is easily
      harvested with minimal potential donor site morbidity. Eight SLILs and NFCLs were
      harvested from fresh-frozen cadavers. Biomechanical extensometry testing was
      performed using an Instron 1000 machine. A 5-mm-wide central portion of the NFCL
      was tested since this width was compatible with the technical aspects of
      reconstructing the SLIL. Both ligaments were tested for elastic properties,
      including stiffness, load to failure, and deformation to failure. Mean length of
      the NFCL was 7.6 mm (range, 5.5-8.5 mm). Stiffness of the NFCL was 10.6 x 10(5)
      Nm (range, 8.0-13.0 Nm) compared with 14.4 x 10(5) Nm for the SLIL (range, 10.0
      19.5 Nm). Peak load to failure for the NFCL was 1,980 N (range, 1,530-2,940 N)
      compared with 2,940 N for the SLIL (range, 1,780-4,050 N). Total elongation to
      failure for the NFCL was 2.50 mm (range, 1.7-3.2 mm) compared with 3.2 mm for the
      SLIL (range, 2.1-5.2 mm). Thus, the biomechanical characteristics of the NFCL
      were found to be very similar to those of the SLIL. Having established the
      biomechanical similarities of the 2 ligaments, we are currently using the NFCL to
      reconstruct the sectioned SLIL in a fresh-frozen cadaver model. Early results
      suggest that this procedure is feasible for restoration of normal kinematics of
      the wrist.

PMID- 9763268
TI  - Wrist arthrodesis after failed wrist implant arthroplasty.
AB  - Wrist arthroplasty has not achieved large success to date, and there are patients
      with failures in their procedures who will need arthrodesis. We review our
      experience in revising a wrist implant arthroplasty to an arthrodesis with a
      block graft of fresh-frozen allograft femoral head or iliac crest bone graft.
      Fixation was achieved with an intramedullary Steinmann pin. Ten patients with 12
      failed wrist implants required wrist arthrodesis; 7 had wrist arthrodesis with a
      bulk allograft femoral head, 4 with an iliac crest bone autograft, and 1 without
      a bone graft. After an average follow-up period of 5 years, all patients were
      pain free and fusion had been achieved. Complications included 1 patient with
      acute carpal tunnel syndrome, 2 patients with nonunions requiring secondary bone
      grafting procedures, and 2 patients requiring revisions of their intramedullar
      pins. In both nonunions, iliac crest bone graft was used for the initial
      arthrodesis. All the patients were satisfied. Arthrodesis after failed wrist
      implant arthroplasty is a satisfactory procedure, and a fresh-frozen allograft
      can be used effectively in wrist fusion.

PMID- 9763269
TI  - Arthroscopic evaluation of radial osteotomy for Kienbock's disease.
AB  - To determine whether osteoarthritic changes of the perilunate articular cartilage
      improve following radial osteotomy for Kienbock's disease and correlate with
      clinical results, arthroscopic examination was performed in 18 patients
      concurrently with radial osteotomy and at the time of removal of implants after
      an average of 21 months. Clinical results were satisfactory. All patients
      improved the preoperative level of pain. Wrist function was improved in range of
      motion and grip strength. Radiographic findings also demonstrated prevention of
      further collapse of the lunate. However, follow-up arthroscopic examination
      revealed progression of osteoarthritis in the area of the lunate in two thirds of
      the cases. There was no correlation between arthroscopic observations and
      clinical results. A long-term follow-up period is therefore advocated for
      evaluation of radial osteotomy because of the possibility of additional
      progression of osteoarthritic changes.

PMID- 9763271
TI  - Pressure distribution in the distal radioulnar joint.
AB  - Measurement of the pressure distribution within the distal radioulnar joint was
      performed in fresh cadaver forearms at varying positions of forearm rotation.
      Axial loads of 0 N, 36 N, and 89 N were applied to the wrist flexors and
      extensors. At neutral forearm rotation and application of 89 N axial load, an
      average of 12.5% of the sigmoid notch area was in contact with the ulna. Analysis
      of the pressure plots reveals that in pronation, the pressure was concentrated in
      the dorsal portion of the sigmoid notch and that in supination the pressure was
      distributed in the palmar portion.

PMID- 9763270
TI  - Ulnar shortening for triangular fibrocartilage complex tears associated with
      ulnar positive variance.
AB  - Twenty-five patients with triangular fibrocartilage complex (TFCC) tears
      associated with ulnar positive variance who did not respond to conservative
      management were treated by ulnar shortening. The follow-up period averaged 35
      months. All patients complained of pain, restricted forearm rotation, and
      weakness of grip. Arthroscopy was performed in 23 of 25 wrists to assess the
      status of the TFCC and the degree of the degenerative change of the proximal
      aspect of the lunate and triquetrum. Arthroscopic findings consisted of 15 class
      1 and 8 class 2 tears according to Palmer's classification. When the TFCC showed
      a traumatic flap tear, only the torn flap was removed arthroscopically. Ulnar
      shortening averaged 3 mm. Transverse osteotomies healed in all patients at a mean
      postoperative time of 7 weeks. Twenty-three patients had either complete relief
      or occasional mild pain of the wrist. Two patients with persistent pain had
      additional procedures performed. Postoperative x-ray films revealed slight
      degenerative changes at the distal radioulnar joint in 7 patients. Complications
      included 1 reflex sympathetic dystrophy and 2 fractures through the osteotomy
      site after early plate removal. Ulnar shortening is a useful procedure for TFCC
      tears associated with ulnar positive variance.

PMID- 9763272
TI  - Un-united fractures of the distal radius: a report of 12 cases.
AB  - The treatment of 12 distal radius nonunions in 11 patients over a 24-year period
      is presented. The average age of the patients was 55 years (range, 35-72 years).
      The comorbid medical conditions in the patients with these fractures included
      diabetes mellitus, peripheral vascular disease, psychiatric disorders,
      alcoholism, peripheral neuropathy, scleroderma, and morbid obesity. Nine of the
      un-united fractures in 8 patients had insufficient metaphyseal bone to allow
      internal fixation; 6 of these fractures were treated with a wrist arthrodesis.
      Three un-united fractures in 3 patients had sufficient supporting bone to permit
      correction of the nonunion and preservation of the radiocarpal joint. Three
      nonunions in 3 patients were treated without further surgery. Bony union was
      achieved in all 9 nonunions managed operatively (6 wrist arthrodeses and 3 open
      reductions).

PMID- 9763273
TI  - Recurrent dorsal angulation of the distal radius fracture during dynamic external
      fixation.
AB  - Thirty-three fractures of the distal radius treated with a dynamic external
      fixator (that allowed for wrist motion between 2 to 4 weeks after surgery) were
      analyzed, focusing on loss of fracture reduction during external fixation.
      Fractures with preoperative dorsal angulation greater than 20 degrees and those
      involving the distal radioulnar joint had a significantly larger loss of
      reduction of dorsal angulation (8.9 degrees and 6.9 degrees, respectively) than
      fractures with less severe preoperative dorsal angulation or those with an intact
      distal radioulnar joint (3.0 degrees and 2.6 degrees, respectively). In contrast,
      preoperative radial shortening (>2 mm) and involvement of the radiocarpal joint
      did not significantly increase the loss of dorsal angulation. Neither of the 2
      dynamic external fixation systems studied consistently stabilized Colles'
      fractures with preoperative dorsal angulation of greater than 20 degrees or
      involvement of the distal radioulnar joint.

PMID- 9763274
TI  - Load relaxation and forces with activity in Hoffman external fixators: a clinical
      study in patients with Colles' fractures.
AB  - A small-frame Hoffman external fixation bar instrumented with strain gauges to
      quantify bending and torsional forces was applied to 4 patients with a displaced
      metaphyseal fracture of the distal radius. Measurements were taken during surgery
      as well as at 1, 3, and 6 weeks after surgery during activities of daily living
      and hand therapy mobilization. Radiographs also were taken before and after
      reduction and at each subsequent visit. Force decay occurred after reduction of
      the fracture, averaging only 26% of the initial distraction forces by 5 minutes.
      These forces plateaued and did not significantly change over the subsequent 40
      minute observation period. There was no correlation between carpal height index
      and the forces measured in the external fixator. Significant changes in external
      fixator forces were measured during activities of daily living and hand therapy
      mobilization, but these returned to baseline after the activities were performed.
      The most provocative activities studied were twisting a doorknob and lifting
      heavy objects. These activities should be performed with caution by patients with
      unstable distal radial fractures.

PMID- 9763275
TI  - Pseudoaneurysm of the ulnar artery occurring after fracture of the distal radius
      and ulna: a case report.
AB  - A case of pseudoaneurysm of the ulnar artery occurring after distal radius and
      ulna fracture is presented. This case illustrates an uncommon complication
      following a fairly common injury.

PMID- 9763276
TI  - Forearm muscle activation during power grip and release.
AB  - The position of the hand during power grip is well-described, but the normal
      phasic activity of the extrinsic forearm muscles during power grip and release is
      unknown. People with neurologic impairment may have inadequate power grip or
      release because of abnormal muscle timing. This study describes the timing of the
      forearm muscles in 10 normal subjects during power grip and release, which was
      evaluated using electromyography. During power grip, subjects had consistent
      timing patterns for extrinsic finger motors and different but individually
      consistent patterns for wrist motors. This finding supports our hypothesis that
      different individuals habitually use a specific motor strategy and an intact
      central nervous system allows them to change their motor strategy to adapt to new
      environmental parameters.

PMID- 9763277
TI  - The effect of shear stress on fibroblasts derived from Dupuytren's tissue and
      normal palmar fascia.
AB  - This study examines the real-time intracellular calcium changes of palmar fascia
      from normal and Dupuytren's diseased fibroblasts in response to shear stress. The
      real-time cytosolic calcium changes were measured using fluorescence microscopy
      image processing. The preconfluent primary cultured cells were exposed to 1
      minute of flow at 25 dyne/cm2 after a 2-minute baseline of no flow. Additionally,
      the cells were exposed to an influx of Hank's buffered saline solution with 2%
      newborn bovine serum to examine the response to serum-born (chemical) agonists.
      Cytosolic calcium changes were measured as the percentage change over the 2
      minute baseline of the mean [Ca2+]i peak. The mean change of the peak [Ca2+]i
      response of the normal palmar fascia was significantly greater than that of the
      cells from the Dupuytren's nodular and perinodular tissue. The response to the
      chemical agonist showed a robust but not statistically different response between
      the 3 cell types. Our work supports the hypothesis that palmar fascia responds to
      mechanical stress, specifically laminar fluid flow. These findings may help to
      explain that an underlying abnormality in the cells of the palmar fascia may be
      expressed by exposure to laminar fluid flow, a physical signal, rather than a
      chemical agonist.

PMID- 9763278
TI  - Simplified Sauve-Kapandji procedure.

PMID- 9763279
TI  - Unit of measurement: newton (N) versus kilogram force (kgf)

PMID- 9763282
TI  - Staged opposition transfer.

PMID- 9763281
TI  - Pain responses in patients with upper-extremity disorders.

PMID- 9763280
TI  - Pain responses in patients with upper extremity disorders.

PMID- 9763283
TI  - Physeal growth arrest of the distal phalanx of the thumb in an adolescent
      pianist: a case report.

PMID- 9763284
TI  - Organisation and informational content of the Theileria parva genome.
AB  - When compared with other Apicomplexan organisms, Theileria parva has an
      exceptionally small, 10-12 Mbp, genome. There are only 4 chromosomes, each in the
      Mbp range, and a complete physical map, based on SfiI linking data, is available
      for each one. A number of genes and cDNAs have been mapped to specific SfiI
      fragments. Telomeres consist of the simple repeat sequence typical of chromosomal
      ends but sub-telomeric homologies do not extend beyond 5 kbp. The only dispersed
      repetitive sequences identified to date are minisatellites, but these are found
      on a subset of SfiI fragments. There are clusters of distinct multicopy sequences
      which contain ORFs. However, the majority of parasite protein coding genes are
      present in a single copy. They have a compact structure, exhibit a bias in codon
      usage and non-translated regions are small. Introns, if present, are unusually
      short. Overall, the genome contains remarkably little repetitive, non-coding DNA.
      The parasite mitochondrial DNA is linear in structure, has a limited protein
      coding capacity and fragmented rRNA genes and its telomeres contain inverted
      repeat sequences.

PMID- 9763285
TI  - Characterization of developmentally-regulated activities in axenic amastigotes of
      Leishmania donovani.
AB  - Leishmania donovani is an obligatory intracellular parasite which cycles between
      the midgut of sand flies (extracellular promastigote) and the phagolysosomes of
      mammalian macrophages (intracellular amastigote). Promastigotes have been readily
      cultured, whereas axenic cultures of amastigotes have only recently been
      developed. A new method for in vitro differentiation of L. donovani promastigotes
      into amastigotes is presented, in which promastigotes are exposed to
      environmental changes that mimic the in vivo process. First, promastigotes are
      subjected to 37 degrees C + 5% CO2 for 24 h, and then are shifted to pH 5.5.
      Under these conditions, differentiation is completed within 120 h. In the reverse
      process, amastigotes are induced to differentiate back to promastigotes by
      transferring them to promastigote growth conditions (medium 199 at pH 7.4 and 26
      degrees C). Axenic amastigotes closely resemble animal-derived amastigotes. They
      manifest all seven proteins of the amastigote-specific A2 gene family. They down
      regulate lipophosphoglycan (LPG) synthesis and do not express it on their
      surface. LPG is up-regulated 2 h after inducing amastigotes to differentiate to
      promastigotes. Within 6 h, parasites resume the promastigote level of this
      molecule, although differentiation is completed only after 48 h. Axenic
      amastigotes also express amastigote-like metabolic activities of proline uptake,
      as well as thymidine and proline incorporation. In conclusion, the results
      indicate that the method developed for in vitro differentiation of L. donovani
      promastigotes to amastigotes is efficient and yields organisms resembling animal
      derived amastigotes. Being able to induce in vitro differentiation of L. donovani
      provides us with an excellent tool to study Leishmania development and
      differentiation.

PMID- 9763286
TI  - Characterisation of a Cryptosporidium parvum-specific cDNA clone and detection of
      parasite DNA in mucosal scrapings of infected mice.
AB  - A cDNA library was constructed using total RNA extracted from oocysts and
      sporozoites of the protozoan parasite Cryptosporidium parvum. The expression
      library was screened with an anti-C. parvum antiserum and a clone, Cp3.4, with a
      2043 bp insert, was extracted. Southern blot analysis demonstrated a single copy
      gene that was located on a 1.6 Mb chromosome. The gene was found to be C. parvum
      specific as Cp3.4 did not cross-hybridise with chromosomal DNA from three other
      apicomplexan parasites. The cDNA encodes a polypeptide with a predicted membrane
      helix at its C-terminal end which is flanked by stretches of acidic amino acids.
      Overall, the polypeptide has a low isoelectric point (pI) of 3.94. A total of 21
      glycine/proline-rich octapeptides were identified which represented variations of
      a consensus sequence. The function of this protein is yet unknown. Using Cp3.4
      specific PCR primers, this C. parvum gene could be amplified from as little as
      0.8 pg of purified parasite DNA in a single polymerase chain reaction. Less than
      0.1 ng of DNA from the ileum mucosa of immunosuppressed adult mice that had been
      infected with C. parvum oocysts was required to detect the parasites. In non
      immunosuppressed mice that were infected and which did not shed oocysts in
      numbers detectable by acid-fast staining, parasite development could be detected
      in 25 ng of total mucosa DNA. This PCR approach may be a valuable technique for
      the detection of parasite infections in situations where conventional staining
      methods fail, such as chronic, low-grade infections or the detection of parasites
      in potential reservoir hosts.

PMID- 9763287
TI  - Phylogenetic analysis of Theileria and Babesia equi in relation to the
      establishment of parasite populations within novel host species and the
      development of diagnostic tests.
AB  - The divergence of parasites is important for maintenance within an established
      host and spread to novel host species. In this paper we have carried out
      phylogenetic analyses of Theileria parasites isolated from different host
      species. This was performed with small subunit ribosomal RNA sequences available
      in the data bases and a novel sequence amplified from Theileria lestoquardi DNA.
      Similar phylogenetic studies were carried out with sequences representing the
      major merozoite/piroplasm surface antigen (mMPSA) from the data base, and novel
      sequences representing 2 mMPSA alleles from T. lestoquardi, a full length
      sequence of a Theileria taurotragi mMPSA gene and partial sequences of two new
      allelic variants of the Babesia equi mMPSA gene homologue. The analysis indicated
      that the pathogenic sheep parasite T. lestoquardi has most probably evolved from
      a common ancestor of T. annulata. Interestingly, the level of mMPSA sequence
      diversity found for T. lestoquardi was surprisingly low, while diversity between
      the B. equi sequences was higher than that found within any of the classical
      Theileria species. The possible implications of these results for the
      establishment of Theileria parasites within novel species are discussed.
      Extensive cross-reactivity of a range of antisera was found when tested against
      recombinant mMPSA polypeptides from different Theileria (including B. equi)
      species. The cross-reactivity between mMPSA polypeptides and sequence diversity
      are relevant for the development of species specific diagnostic tests.

PMID- 9763288
TI  - Hgm1, a novel male-specific gene from Heterodera glycines identified by
      differential mRNA display.
AB  - The plant parasitic nematode Heterodera glycines is amphimictic: populations
      consist of both male and female individuals that reproduce sexually. However,
      under conditions of environmental stress, unbalanced male and female sex ratios
      are found. This observation requires an explanation of how sexual fate is
      determined in these nematodes. As a step towards identifying genes that are
      differentially regulated between male and female nematodes we have used cDNA
      differential display to screen for male-specific cDNA sequences. These studies
      have led to the isolation of a full-length male specific cDNA, Hgm1, that is up
      regulated in H. glycines males. Sequence analysis of this cDNA reveals that it
      represents a novel gene which encodes a 49.5 kDa acidic protein with a pI of 4.72
      and a predicted 21 amino acid leader sequence. Neither the nucleotide nor the
      predicted amino acid sequence of this gene show any homology to sequences in the
      databases suggesting that Hgm1 is a previously uncharacterised gene. Here we
      report the isolation, molecular characterisation and expression profile of Hgm1.

PMID- 9763289
TI  - Biochemical and molecular properties of the Trypanosoma brucei alternative
      oxidase.
AB  - The protozoal parasite Trypanosoma brucei depends on a mitochondrial non
      cytochrome terminal oxidase known as the trypanosome alternative oxidase (TAO) in
      its mammalian host. We have recently cloned the cDNA from T. brucei bloodstream
      form and have characterized a 33 kDa mitochondrial protein as TAO. Here we report
      that the TAO is a single copy gene in T. brucei and its expression is down
      regulated at the level of transcript abundance during differentiation from the
      bloodstream to the procyclic trypanosomes. Like other alternative oxidases (AOXs)
      cloned from different plants and fungi, TAO possesses the conserved sequences at
      the centrally located predicted membrane spanning domains and the signature
      sequence at the C-terminal hydrophilic domain for a pair of putative iron binding
      motifs (E-X-X-H). Phylogenetic analysis of the deduced protein sequences of eight
      different alternative oxidases cloned from different plants and fungi revealed
      that TAO is more closely related to the alternative oxidases of the fungi clade
      than that of plants. TAO has been functionally expressed in Escherichia coli. In
      the first of the two putative iron binding motifs, site-directed mutagenesis of
      E215 to A, L, N and Q resulted in the loss of the ability of the TAO gene to
      complement the heme deficiency of the E. coli mutants (SASX41B and GE1387) by
      conferring on them a CN-insensitive pathway of respiration. The conservative
      substitution of E215 by aspartate and histidine reduced the growth of the E. coli
      auxotrophs by approximately 80%. The mutations apparently did not have any effect
      on the stability of the expressed protein as revealed by the immunoblot analysis
      of the bacterial protein using TAO monoclonal antibody, which we have developed.
      Together, these points suggest that E215 plays an important role in the function
      of TAO. The steady state level of TAO mRNA is down-regulated in the procyclic
      stage presumably accounting for the low levels of TAO protein in these forms.

PMID- 9763290
TI  - Divergent evolutionary constraints on mitochondrial and nuclear genomes of
      malaria parasites.
AB  - Genetic variation among malaria parasites has important consequences with regard
      to drug resistance, pathogenicity, immunity, transmission, and speciation. In
      this regard, malaria parasites have been shown to display a high degree of inter-
      and intra-species genetic divergence. The nuclear genomes of Plasmodium
      falciparum, Plasmodium yoelii, and Plasmodium gallinaceum are vastly divergent
      yet share a similar codon usage and total A/T content of approximately 82%. This
      is in contrast to other primate-specific species including P. vivax which have an
      A/T content of approximately 67%. To assess the effects of this evolutionary
      divergence on the conservation of gene content, organization, and codon usage in
      the mitochondrial DNA (mtDNA) of malaria parasites, we have cloned and sequenced
      the mitochondrial genome of Plasmodium vivax, and compared it with the mtDNAs of
      P. falciparum, P. yoelii, and P. gallinaceum. The P. vivax mitochondrial genome
      was found to be 5990 base pairs in length, and displayed a gene organization
      identical to that of P. falciparum, P. yoelii, and P. gallinaceum. Furthermore,
      there was a remarkable 90% conservation of sequence identity between the
      mitochondrial genomes of all four species. As an example of intra-species
      conservation, comparison of mtDNAs from two independently cloned P. falciparum
      isolates, Malay Camp and C10, revealed only a single nucleotide substitution. A/T
      content of the P. vivax mitochondrial genome was found to be identical to other
      species of Plasmodium, hence, we have postulated that the mitochondrial genomes
      of malaria parasites were refractory to the evolutionary shifts in nucleotide
      content seen among the nuclear genomes of malaria parasites. Among different
      Plasmodium species, the second position of mitochondrial codons were found to be
      the least prone to substitutions and displayed a significant bias in pyrimidines.
      These aspects of mitochondrial codon usage were distinct from the nuclear genome
      and may reflect functional aspects of decoding by the mitochondrial translational
      system.

PMID- 9763291
TI  - Identification of stage-regulated and differentiation-enriched transcripts during
      transformation of the African trypanosome from its bloodstream to procyclic form.
AB  - Trypanosoma brucei undergoes dramatic stage-specific changes in surface antigen
      expression, metabolic development, cellular morphogenesis and cell-cycle control.
      These events can be studied in detail during the transition between the
      bloodstream stumpy stage and the tsetse fly midgut procyclic form. This
      differentiation can be induced in vitro, is synchronous in the population and
      there are abundant markers for stage-regulated and differentiation events. We
      have used this differentiation system to investigate the role of de novo
      transcription during different phases of this well-characterised cellular
      transformation. Our experiments implicate early transcriptional involvement in
      shedding of the variable surface glycoprotein coat, cell restructuring and cell
      cycle re-entry. The synchrony of differentiation has also been exploited to
      identify transcripts which define distinct regulated processes during this
      differentiation. The transcripts identified provide good coverage of the
      different molecular regulation events that accompany this life-cycle
      transformation. These included a surface antigen gene (encoding procyclin/PARP),
      a cell cycle regulated component (encoding histone H2B), a homologue of the
      Leishmania activated protein kinase C receptor (LACK) and a putative gene for sub
      unit VI of cytochrome c oxidase.

PMID- 9763292
TI  - Selection for activation of a new variant surface glycoprotein gene expression
      site in Trypanosoma brucei can result in deletion of the old one.
AB  - The African trypanosome Trypanosoma brucei expresses the active variant surface
      glycoprotein (VSG) gene in a telomeric VSG gene expression site. We have
      generated trypanosomes with a neomycin resistance gene inserted behind an active
      VSG gene expression site promoter, and a hygromycin resistance gene behind a
      silent one. By alternating drug selection, we could select for trypanosomes that
      had switched between the two marked VSG gene expression sites. Surprisingly,
      trypanosomes that had activated a new VSG gene expression site had often lost the
      old one. Using polymerase chain reaction (PCR), we screened large numbers of
      switched trypanosomes and found that sequences lost invariably included the drug
      marker near the promoter, as well as the telomeric VSG gene many tens of
      kilobases away. We postulate that stable activation of a new expression site
      requires silencing of the old one. If silencing does not occur at a sufficient
      rate by normal switch-off, stable activation of the new site can only occur if
      the old site is lost in random deletion events. The fact that we pick up these
      normally infrequent deletions, indicates that inactivation of the old VSG
      expression site could be rate limiting during switching in our strain of T.
      brucei.

PMID- 9763294
TI  - The mini-exon gene: a genetic marker for zymodeme III of Trypanosoma cruzi.

PMID- 9763293
TI  - The mitochondrial genome of Onchocerca volvulus: sequence, structure and
      phylogenetic analysis.
AB  - The complete DNA sequence of the mitochondrial genome of Onchocerca volvulus is
      described. The O. volvulus mitochondrial genome is 13747 bp, slightly smaller
      than the mitochondrial genomes of the nematodes Ascaris suum and Caenorhabditis
      elegans, and the smallest metazoan mitochondrial DNA molecule reported to date.
      The O. volvulus mitochondrial genome contains genes for two ribosomal RNAs, 22
      transfer RNAs and 12 proteins. Consistent with the small size of the genome, four
      gene pairs overlap and eight contain no intergenic regions. Only 17 intergenic
      regions are found, ranging in size from 1 to 46 bp. As in C. elegans and A. suum,
      the O. volvulus mitochondrial genome lacks an open reading frame encoding ATPase
      subunit 8, and all genes are apparently transcribed in the same direction.
      However, the mitochondrial gene order of O. volvulus differs from that of A.
      suum, C. elegans and other metazoan mitochondrial genomes. A total of 20 of the
      22 transfer RNAs encoded in the O. volvulus mitochondrial genome have the
      potential to fold into secondary structures lacking the TpsiC arm, as has been
      reported in other nematodes. The genome exhibits a striking codon bias, with
      15/20 amino acids having a single codon preference of > 70%.

PMID- 9763295
TI  - Purification and characterization of UDP-N-acetylglucosamine pyrophosphorylase
      from encysting Giardia.

PMID- 9763297
TI  - Construction and characterisation of a genomic PAC library of the intestinal
      parasite Cryptosporidium parvum.

PMID- 9763296
TI  - Cloning and characterization of Leishmania tarentolae adenine
      phosphoribosyltransferase.

PMID- 9763298
TI  - Plasmodial serine repeat antigen homologues with properties of schizont cysteine
      proteases.

PMID- 9763299
TI  - Telomeric features of Theileria parva mitochondrial DNA derived from cycle
      sequence data of total genomic DNA.

PMID- 9763300
TI  - An RCC1-type guanidine exchange factor for the Ran G protein is found in the
      Plasmodium falciparum nucleus.

PMID- 9763301
TI  - Adenylate cyclases in keratinocytes: FRSK cells express types I, II, III, IV, VI
      and VIII, and 1,25(OH)2D3, retinoic acid and TPA augment forskolin-induced cyclic
      AMP accumulation in the absence of altered isozyme expression.
AB  - Molecular cloning analysis has detected at least nine adenylate cyclase isozymes
      in mammalian tissues. Using fetal rat skin keratinocytes (FRSK), we investigated
      adenylate cyclase expression and its modulation by 1,25-dihydroxyvitamin D3
      (1,25(OH)2D3), a retinoid (Ro10-1670), and 12-O-tetradecanoylphorbol-13-acetate
      (TPA). Reverse transcription polymerase chain reaction (RT-PCR) indicated that
      FRSK contain adenylate cyclases I, II, III, IV, VI and VIII. Treatment with
      1,25(OH)2D3 (1 x 10(-7) M), Ro10-1670 (1 x 10(-6) M), and TPA (100 ng/ml)
      resulted in increased forskolin-induced cyclic AMP accumulation by FRSK cells and
      normal human keratinocytes (NHK). Quantitative RT-PCR and Western blot analysis,
      however, detected no alteration in mRNA and protein levels of each adenylate
      cyclase isozyme for at least 48 h. These results indicate that FRSK contain at
      least six (I, II, III, IV, VI and VIII) adenylate cyclase isozyme mRNAs,
      suggesting a complex regulatory mechanism of cyclic AMP generation in
      keratinocytes. Although 1,25(OH)2D3, Ro10-1670, and TPA augmented forskolin
      induced cyclic AMP accumulation, they do not seem to affect the expression of
      specific adenylate cyclase isozymes by FRSK cells.

PMID- 9763302
TI  - Inhibition of skin 11beta-hydroxysteroid dehydrogenase activity in vivo
      potentiates the anti-inflammatory actions of glucocorticoids.
AB  - Synthetic forms of glucocorticoids (GCs) with high potency are widely used to
      treat a number of dermatological conditions having an inflammatory or autoimmune
      etiology. While GCs are generally effective in their ability to suppress
      inflammatory processes, their chronic use can lead to detrimental systemic side
      effects. In this report, we describe a method by which the localized
      antiinflammatory potential of the natural GC cortisol can be significantly
      augmented without increasing the risk of negative systemic effects. 11Beta
      hydroxysteroid dehydrogenase (11beta-HSD) is a naturally occurring enzyme in the
      skin. 11Beta-HSD functionally converts biologically active 11-hydroxy GCs to
      their biologically inactive 11-keto metabolites, thereby limiting the ability of
      GCs to mediate antiinflammatory activities. By topically applying specific
      inhibitors of 11beta-HSD in conjunction with low doses of GCs, the
      antiinflammatory properties of cortisol can be significantly potentiated. It was
      observed that the generation of the effector phase of contact hypersensitivity
      (CH) responses could be suppressed by this combined treatment under conditions
      where the 11beta-HSD inhibitor alone, or cortisol alone were only minimally
      effective. Only the combined treatment was effective at inhibiting the
      progression of an ongoing CH response.

PMID- 9763303
TI  - Differential response of basal keratinocytes in a human skin equivalent to
      ultraviolet irradiation.
AB  - The human skin equivalent (HSE) provides a convenient model system for studying
      the cellular responses of basal keratinocytes to UV irradiation. HSEs,
      constructed by overlaying a collagen-fibroblast matrix with epidermal cells, were
      raised to an air-liquid interface to promote epidermal differentiation. HSEs were
      exposed to ultraviolet radiation from a 500-W Hot Quartz Hanovia therapeutic
      sunlamp, at a total dose of 100 J/m2. The HSEs were then frozen every 4 h over a
      48-h period and cryosectioned. For each time period, the expression of beta1
      integrin and cyclin E, p53, or Bcl-2 were quantified using dual
      immunolocalization. Basal cells expressing beta1 integrin were divided into two
      subpopulations, denoted beta1high or beta1low. The proportion of beta1high
      keratinocytes expressing Bcl-2 and cyclin E increased significantly 4 and 8 h,
      respectively, after exposure to UV; during the subsequent 16 h, this basal cell
      subpopulation expressed p53. By contrast, significant numbers of beta1low basal
      keratinocytes expressed p53, but not Bcl-2. These results suggest that beta1high
      and beta1low populations of basal epidermal cells in HSEs respond differently to
      UV irradiation.

PMID- 9763304
TI  - Alpha-MSH regulates interleukin-10 expression by human keratinocytes.
AB  - Normal human keratinocytes (HKC) are able to synthesize alpha-MSH. Because the
      production of alpha-MSH by HKC is induced significantly by ultraviolet B
      radiation, the involvement of keratinocyte-derived alpha-MSH in UV-induced
      immunosuppression has been suggested. The induction of the antiinflammatory
      cytokine IL-10 in monocytes is a major mechanism in the antiinflammatory actions
      of alpha-MSH. In the present study, HKC were investigated for their ability to
      produce IL-10 after alpha-MSH stimulation. HKC were obtained from the skin of
      human female breast sections and either left untreated or treated with 0.01 or
      0.1 microg/ml alpha-MSH for different times. Using RT-PCR, HKC were shown to
      express IL-10 mRNA even under basal conditions, and treatment with alpha-MSH
      increased expression. Only minimal concentrations of IL-10 protein were detected
      in supernatants from the alpha-MSH-stimulated cultures. To the best of our
      knowledge this is the first report of IL-10 expression by cultured HKC after
      alpha-MSH stimulation. Further studies are needed to determine the biological and
      therapeutic relevance of these findings.

PMID- 9763305
TI  - Histamine enhances UVB-induced IL-6 production by human keratinocytes.
AB  - Histamine, an important mediator in immediate-type hypersensitivity, is elevated
      in the skin of patients with atopic dermatitis and is considered to play a
      pathogenic role in atopic dermatitis. In this study, to elucidate the mechanism
      of sun exposure-induced exacerbation of skin lesions in atopic dermatitis, we
      examined the effect of histamine on proinflammatory cytokine production of
      keratinocytes induced by ultraviolet (UV) B irradiation. Cultured human
      keratinocytes were irradiated with 30 mJ/cm2 of UVB and incubated with histamine
      over the concentration range 10(-7) to 10(-4) M, and the IL-1alpha and IL-6
      released into the medium were measured using an ELISA. Histamine weakly
      stimulated IL-6 production by itself. However, together with UVB, it
      synergistically enhanced IL-6 production and the amount of IL-6 mRNA as estimated
      by reverse-transcription polymerase chain reaction (RT-PCR). Histamine had a dose
      dependent effect which was maximal at a concentration of 10(-5) M, and had no
      effect on the kinetics of IL-6 production. In contrast, histamine had no effect
      on IL-1alpha production by keratinocytes. The effect of histamine was completely
      blocked by pyrilamine, an H1 receptor antagonist, and mimicked by the H1 receptor
      agonist, 2-methylhistamine. Whereas the H2 receptor antagonist, cimetidine,
      slightly inhibited the effect of histamine and the effect of the H2 receptor
      agonist, 4-methylhistamine, was minute. These results show that histamine
      augments UVB-induced IL-6 production by keratinocytes predominantly via the H1
      receptor at the level of transcription. This suggests a contributory role for
      histamine in the exacerbation of atopic dermatitis induced by sun exposure.

PMID- 9763306
TI  - Histopathological assessment of localized proliferation in cases of Bowen's
      disease using immunostaining and a laser cytometer.
AB  - In order to evaluate the localized proliferative activity of intratumor cells in
      Bowen's disease using tissue sections, skin specimens from ten patients were
      compared with skin samples from seven normal individuals for their expression of
      proliferating cell nuclear antigen (PCNA), Ki-67 immunostaining and intranuclear
      DNA contents, quantitated with a laser cytometer (LCM). In normal epidermis, the
      largest proportion of PCNA- and Ki-67-positive cells was observed in the basal
      cell layer, with the amounts decreasing through the suprabasal cell layer towards
      the prickle cell layer. Examination by LCM also revealed the highest average
      fluorescence intensity of individual nuclei in the basal cell layer and, as with
      the immunohistological parameters, reducing towards the upper layer of the
      epidermis. In the Bowen's disease tissue sections, the largest proportion of PCNA
      and Ki-67-positive cells was found in contact with the basement membrane (base
      of the tumor), with lower amounts in the center of the tumor nest and in the
      marginal epidermis. The average fluorescence intensities of individual nuclei
      were in line with these results. These results show that tumor cells distributed
      in Bowen's disease tumor nests have different proliferative activities depending
      on their location.

PMID- 9763307
TI  - The genetic basis of "Scarsdale Gourmet Diet" variegate porphyria: a missense
      mutation in the protoporphyrinogen oxidase gene.
AB  - The porphyrias are disorders of porphyrin or porphyrin-precursor metabolism that
      result from inherited or acquired aberrations in the control of the porphyrin
      heme biosynthetic pathway. Variegate porphyria (VP), one of the acute hepatic
      porphyrias, is characterized by a partial reduction in the activity of
      protoporphyrinogen oxidase (PPO), and recently, mutations in the PPO gene on
      chromosome 1q22-23 have been described. Our purpose was to identify the
      underlying genetic lesion in a severely affected patient with VP and to detect
      the silent mutation carriers in her family. The disease in this patient was
      precipitated by carbohydrate restriction as outlined in the "Scarsdale Gourmet
      Diet". Our mutation detection and confirmation strategy included PCR, automated
      sequencing, and restriction enzyme digestion. We identified a missense mutation
      in the patient and five family members. The mutation consisted of a previously
      unreported C-to-T transition in exon 5 of the PPO gene, resulting in the
      substitution of arginine by cysteine, designated R152C. This arginine residue is
      evolutionarily highly conserved in humans, mice, bacteria, yeast, and plants,
      indicating the importance of this residue in PPO. Our study established that a
      missense mutation in the PPO gene was the underlying mutation in this patient
      with VP and explained the occurrence of the phenotype in this family.

PMID- 9763308
TI  - A study on Epstein-Barr virus in erythema multiforme.

PMID- 9763309
TI  - Influence of topical tretinoin on skin lipid production in vivo.

PMID- 9763310
TI  - The glycoprotein of the carcinoembryonic antigen (CEA) gene family expressed on
      epithelial keratinocytes in viral warts.

PMID- 9763311
TI  - Expression of melanoma-associated antigens in short-term melanoma cultures
      detected by RT-PCR and subsequent ELISA.

PMID- 9763312
TI  - Morphological and genetic characterisation of Cryptosporidium oocysts from
      domestic cats.
AB  - Faecal samples were collected from domestic cats in the metropolitan area of the
      city of Perth, Western Australia, and screened for the presence of
      Cryptosporidium by both microscopy and PCR. Of 162 samples screened, two were
      positive for Cryptosporidium (a prevalence of 1.2%). Sample Ct33 was from an 18
      month-old female and sample Ct131 from a 12-month-old female. Morphological
      studies revealed oocysts with an average size of 4.6 x 4.0 microm, smaller in
      size than isolates typically seen in humans (5.0 x 4.5 microm). Sequence analysis
      of PCR products showed sequences from cat isolates to be different to previously
      sequenced human and calf isolates, with cat isolates exhibiting 8.1% sequence
      divergence from these isolates. Phylogenetic analysis grouped the cat isolates
      into a distinct group, separate from other C. parvum isolates and Cryptosporidium
      species. These results lend support to the existence of a cat-adapted
      Cryptosporidium strain or species.

PMID- 9763313
TI  - Comparison of three ELISA tests for seroepidemiology of bovine fascioliosis.
AB  - The aim of the present study was to compare the sensitivity, specificity and
      usefulness of the DIG-ELISA, DOT-ELISA and Indirect ELISA tests for determining
      the seroprevalence of fasciolosis in cattle under tropical conditions in Mexico.
      To standardize the tests, positive and negative sera to F. hepatica from 88
      Holstein Freisian adult cows located in an enzootic area of fascioliosis and 88
      crossbred adult cattle from a fluke-free area were used. For the epidemiological
      study, 85 crossbred cattle between 1 to 7 years of age were used. Animals were
      bled every two months, from March 1995 to September 1996 and the sera obtained
      were stored at -70 degrees C, until used. Indirect ELISA showed a sensitivity of
      96.5% and a specificity of 98.8%, DIG-ELISA 97.5% and 80.0% and DOT-ELISA 93.1%
      and 95.4%, respectively. During 1995, Indirect ELISA yielded the highest levels
      of IgG anti-F. hepatica antibodies. However, in 1996, after animal treatment with
      triclabendazole, DIG-ELISA tended to show higher percentages of antibody-positive
      animals, but it was not significantly different (p>0.05) from the other tests.
      Comparisons made in parallel to the faecal sedimentation test demonstrated that
      all serological tests detected higher percentages of positive animals. Only one
      serum out of ten (10%) of Paramphistomum spp. cross-reacted with the DOT-ELISA
      test, but no cross-reaction was observed with sera from animals with other
      parasites. All ELISA tests were highly sensitive and specific; they may be
      recommended for use in seroepidemiological surveys for F. hepatica.

PMID- 9763314
TI  - Coproantigens: early detection and suitability of an immunodiagnostic method for
      echinococcosis in dogs.
AB  - In the present study immunodiagnostic tests for Echinococcus granulosus-specific
      coproantigens have been evaluated. The techniques are based on polyclonal
      antisera collected from dogs experimentally infected with E. granulosus
      protoscoleces. ELISA, Countercurrent immunoelectrophoresis (CCIEP) and Immunodot
      were evaluated for their application in coprodiagnosis. The level of
      coproantigens was detectable on day 7 post-infection and reached a maximum level
      on day 56 as detected by ELISA. Very high O.D values were obtained when faecal
      samples of 7-8 weeks post-infection were used. Besides this, immunodot and CCIEP
      were also tested and the 4th week post-infection samples gave significant
      reactions. It is evident from the results that ELISA was more sensitive and
      detected the coproantigens as early as the first week post-infection whereas
      immunodot and CCIEP detected coproantigens later. The latter methods are rapid,
      cost-effective and can be used to diagnose suspect cases of echinococcosis under
      field conditions. Thus, it is suggested that future studies should be aimed at
      early detection of echinococcosis by a rapid and cost-effective immunodot test.

PMID- 9763315
TI  - Identification and semi-quantitation of Ostertagia ostertagi eggs by enzymatic
      amplification of ITS-1 sequences.
AB  - A region within the first internal transcribed spacer (ITS-1) of the ribosomal
      DNA repeat of Ostertagia ostertagi has been identified that is 408 base pairs
      (bp) in length and is comprised of a 2 x 204 bp repeat. Universal polymerase
      chain reaction (PCR) primers which span this region, as well as a portion of the
      5.8S rDNA, generate a 1011 bp fragment using genomic DNA from O. ostertagi.
      However, these same primers generate only a 600 bp (approximate) fragment using
      DNA from Haemonchus contortus, Cooperia oncophora and Oesophagostomum radiatum,
      as well as other species within the genus Ostertagia. When DNA samples derived
      from adult parasites of the different genera were mixed and simultaneously
      amplified, the O. ostertagi component could be identified within the mixed DNA
      populations. Furthermore, a correlation was observed between relative
      fluorescence intensities of the 1011 bp and the 600 bp PCR fragments and the
      percentage of O. ostertagi DNA within a mixture of parasite DNAs. A similar high
      correlation was obtained between the percentage of O. ostertagi DNA and percent
      O. ostertagi eggs in feces containing eggs of other nematode genera. This
      resulted in the generation of a protocol that can determine the percentage of O.
      ostertagi eggs within a mixed population of gastrointestinal nematode eggs.
      Results indicate a detection equivalent to 0.05 eggs.

PMID- 9763316
TI  - Field efficacy of doramectin pour-on against naturally-acquired, gastrointestinal
      nematodes of cattle in North America.
AB  - Seven studies were conducted under field conditions in North America to evaluate
      the therapeutic efficacy of doramectin in a pour-on formulation at a dosage of
      500 microg/kg (1 ml/10 kg) for cattle harboring naturally-acquired infections of
      gastrointestinal nematodes, including species of Haemonchus, Ostertagia,
      Trichostrongylus, Bunostomum, Cooperia, and Oesophagostomum. In each study, 40 to
      100 cattle were randomly allocated to a saline- or doramectin-treated group in a
      tiered manner based on Day -7 bodyweight. On Day 0, the cattle received either
      saline or doramectin topically, according to their treatment group. Weather and
      safety observations were made following treatment. No adverse reaction to
      treatment was observed at any time during these studies. Fecal egg count (FEC)
      determinations were carried out on each animal on Days -7, 0, 7, 14, and 21.
      Reductions in FEC for the doramectin-treated animals compared to saline-treated
      cattle were > or = 96.0% by Day -7 and > or = 99.0% on Days 14 and 21 for each
      study. Across all studies regardless of weather conditions, the reduction by Day
      21 for the doramectin-treated animals compared to saline controls was 99.7% (p <
      or = 0.0001) and compared to pretreatment levels in doramectin-treated cattle was
      99.9% (p < or = 0.0001). Doramectin pour-on should provide a useful new treatment
      for controlling nematode parasites of cattle.

PMID- 9763317
TI  - Canine filariasis. Importance and transmission in the Baix Llobregat area,
      Barcelona (Spain).
AB  - Field and laboratory studies were performed in order to assess the degree of
      canine dirofilariasis caused by Dirofilaria immitis (Leidy) in the Baix Llobregat
      region, a fluvial area near Barcelona, Spain. A total of 188 dogs were sampled
      between May and August of 1994. Three main areas were chosen: the Western Delta,
      the Eastern Delta and the Northern zone. Simultaneously, a mosquito sampling
      programme was carried out with CO2 light traps, to search for infective larvae
      (L3) of D. immitis. Of the 188 dogs sampled, 38 were positive for at least one of
      the three filaria found: D. immitis 12.8%, Dipetalonema reconditum (Grassi) 3.7%
      and Dipetalonema dracunculoides (Cobbold) 2.7%. Only 1.1% showed a mixed
      infection of both D. immitis and D. dracunculoides. Although Dirofilaria repens
      Raillet et Henry has been found in Spain, it was not found in this study.
      Comparing the three zones of the Baix Llobregat, the Eastern Delta showed the
      highest level of D. immitis (35.3%), probably due to the presence of Aedes
      caspius (Pallas). Despite the effort in sampling the mosquito population, D.
      immitis was not found in any of the 2001 females dissected, belonging to 5
      species.

PMID- 9763319
TI  - Course of the endogenous developmental phase of selected Eimeria species in
      pheasants.
AB  - The localization and duration of developmental stages of Eimeria colchici and
      Eimeria duodenalis were studied histologically. The prepatent period of the most
      pathogenic species from the caeca of pheasants--Eimeria colchici--was 6 days. The
      patent period began on the 7th day and finished on the 11th day post-infection
      with the maximum production of oocysts on days 8-9. In the case of Eimeria
      duodenalis the prepatent period was shorter--4 days, and the duration of the
      patent period was 3-4 days without a significant increase in oocyst production.

PMID- 9763318
TI  - Use of a mathematical model to study the control measures of the cattle tick
      Boophilus microplus population in New Caledonia.
AB  - Boophilus microplus is a common cattle tick of great economic importance in
      various tropical and subtropical countries like New Caledonia. The proposed model
      describes the population dynamics of female Boophilus microplus in the absence of
      resistant ticks. It is a system of six difference equations which can be
      mathematically analyzed. The analysis of the system shows the great importance of
      the eigenvalue denoted by lambda1. The population of ticks increases if lambda1 <
      1 and decreases if lambda1 > 1. The lambda1 eigenvalue depends, in particular, on
      the parasitic surviving rate and encounter rate between the larvae and the cows.
      The treatments decrease the parasitic surviving rate as the agronomic measures
      decrease the encounter rate. This model permits to quantify the conditions of
      treatments (or of the efficacy of a vaccine) and of agronomic measures by which
      the populations are controlled. It shows that the different treatment rhythms and
      the presence or not of the wild or domestic refuges plays a major role on the
      dynamics of tick population.

PMID- 9763320
TI  - Neosporosis in a dog in Italy.
AB  - Clinical neosporosis was diagnosed in a 2-month-old Pit Bull Terrier from Italy.
      Neospora caninum tachyzoites were found in semitendinosus muscle with myositis.
      The diagnosis was confirmed by immunohistochemical staining with anti-N. caninum
      specific antibodies. This is the first report of systemic neosporosis in dogs
      from Italy.

PMID- 9763321
TI  - Limited role of lagomorphs (Oryctolagus cuniculus and Lepus capensis) in the
      dispersion of parasite nematodes of ruminants.
AB  - Rabbits (Oryctolagus cuniculus) and hares (Lepus capensis) were investigated
      under natural conditions for infection with ruminant nematodes, either in the
      condition of close contact with sheep (south-east of France) or unknown contact
      with ruminants (central region and French Champaign). Rabbits and hares were
      poorly infected with sheep digestive tract nematodes: Trichostrongylus
      colubriformis (second record) was encountered in one site and Trichostrongylus
      capricola (a first record) in another site, at very low intensity. Small sheep
      lungworms (Neostrongylus linearis and Cystocaulus ocreatus) were not recorded in
      rabbits grazing common pasture with sheep. Although transmission remained limited
      between lagomorphs and ruminants, it could play a role in the transfer of
      nematode isolates resistant to anthelmintics from one farm to another.

PMID- 9763322
TI  - Experimental infection of inbred mouse strains with Spironucleus muris.
AB  - Four inbred mouse strains: BALB/c ByJ, 129/J, C3H/HeJ, and DBA/lJ, differing in
      major histocompatibility type, were orally inoculated with 2 x 10(5) infectious
      cysts of Spironucleus muris. Fecal samples were collected for fecal cyst output
      prior to infection, and on days 2, 6, 7, 8, 9, 11, 13, 15, and 17 after
      infection. Following necropsy, formalin-fixed intestinal sections were examined
      for the presence of trophozoites. On post-inoculation days 6 and 8, mice of the
      129/J strain shed significantly (p<0.05) fewer cysts than other strains. This
      pilot study suggests that major histocompatibility haplotype may influence
      susceptibility of inbred mouse strains to S. muris.

PMID- 9763323
TI  - Evaluation of 2 methods to assess gingival bleeding in smokers and non-smokers in
      natural and experimental gingivitis.
AB  - The purpose of the present study was to compare the bleeding tendency as elicited
      by probing the marginal gingiva (BOMP) and probing to the bottom of the pocket
      (BOPP) in smokers and non-smokers in natural gingivitis and during experimental
      gingivitis. 11 smokers (sm) and 14 non-smokers (nsm) were recruited. When they
      had less than 20% approximal bleeding sites, they entered a 14-day trial period
      of 'experimental gingivitis'. Subjects returned 30 days later, after resuming
      normal oral hygiene procedures, for a final gingival assessment. A split-mouth
      design was chosen using 2 contra-lateral quadrants for each index (being either
      BOMP or BOPP). A consistently higher bleeding score of approximately 10% was
      observed by probing to the bottom of the pocket. At day 14 with both indices, a
      significant difference between smokers and non-smokers was detected (BOMP:
      sm=15%, nsm=30%; BOPP: sm=27%, nsm=44%). The increment between gingival health
      and experimental gingivitis was significantly higher in non-smokers than in
      smokers but comparable for both indices (BOMP: sm=8%, nsm=23%; BOPP: sm=9%,
      nsm=26%). Probing to the bottom of the pocket results in significantly more
      bleeding in gingival health and gingivitis as compared to probing of the marginal
      gingiva. This shows that evaluation of the gingival condition with BOMP, the
      method of choice with respect to gingivitis, can be used as a parameter for
      inflammation when comparing smokers and non-smokers. The suppressed inflammatory
      response to plaque accumulation, as observed in smokers, indicates that they
      should be identified as a separate group when they participate as panelists in
      (experimentally induced) gingivitis studies.

PMID- 9763324
TI  - Evaluation of the incidence of gingival abrasion as a result of toothbrushing.
AB  - The aims of the present study were: (1) to establish the incidence of gingival
      abrasion as a result of toothbrushing, using a manual and electric toothbrush;
      (2) to establish the influence of filament end-rounding on the incidence of
      gingival abrasion and the efficacy of toothbrushing; (3) to assess whether the
      speed of the electric brush has a feedback-effect on the brushing force used and
      to correlate the incidence of gingival abrasion with force. 2 experiments were
      carried out. In the first experiment, 50 subjects brushed for 3 weeks every other
      day with either a manual (Butler 411) or an electric toothbrush (Braun/Oral-B
      Ultra Plaque Remover-D9). All received brief instructions and were asked to
      abstain from oral hygiene 24 hrs before their appointment. After disclosing the
      teeth and gums with Mira-2-Tone solution, plaque and gingival abrasion were
      assessed. Next, the panelists brushed in a random split-mouth order. After
      brushing and a second disclosing, plaque and abrasion were re-assessed. The
      results showed that the incidence of gingival abrasion was comparable for the
      manual and the D9. Using a similar design as in experiment no. 1, in experiment
      no. 2 a new group of 47 subjects brushed for 3 weeks alternating between the
      Braun/Oral-B Plaque Remover-D7 and D9. At the appointment, the subjects first
      brushed in a split-mouth order with the D9 with 2 different types of endrounding.
      Plaque and abrasion were assessed. Immediately following this brushing exercise,
      the subjects re-brushed with the D7 (2800 rot/min) and the D9 (3600 rot/min)
      during which brushing force was measured. The results of this experiment showed
      that endrounding has no effect on plaque removal but does effect the incidence of
      gingival abrasion. Brushing force is not influenced by the speed of the brushhead
      and no correlation with the incidence of gingival abrasion was observed. In
      conclusion, the results of this study show that gingival abrasion is not
      influenced by brushing force, but is affected by filament endrounding.

PMID- 9763325
TI  - Root conditioning using EDTA gel as an adjunct to surgical therapy for the
      treatment of intraosseous periodontal defects.
AB  - The aim of this clinical study was to compare the treatment outcome following
      root surface conditioning using an EDTA gel preparation in conjunction with
      surgical therapy with that following conventional flap surgery in periodontal
      intraosseous defects. 36 patients, each of them contributing one intraosseous
      defect > or =4 mm in depth participated. Defect sites had a probing pocket depth
      > or =5 mm and bled on probing following hygienic treatment phase. No furcation
      involvement or endodontic complications were present. In the EDTA group, 18
      consecutive patients, defects were treated by root conditioning with EDTA gel for
      3 minutes in combination with surgical therapy. In the control group, 18
      patients, conventional flap surgery was performed without root conditioning.
      Chlorhexidine rinsings 0.2% were prescribed following surgery for 2-3 weeks with
      modified oral hygiene instruction. A strict recall program was implemented
      including professional prophylaxis and oral hygiene reinforcement every 4-6 weeks
      until 6-month re-evaluation. Baseline probing pocket depths and defect depths of
      7.1+/-1.3 mm and 6.9+/-1.6 mm in the EDTA group and 7.6+/-1.9 mm and 6.6+/-1.7
      mm, respectively, in the control group were measured. 6-month clinical results
      showed a significant probing attachment level gain of 1.8+/-1.5 mm and 1.0+/-1.7
      mm in the EDTA and control groups respectively. A probing bone gain of 1.0+/-1.3
      mm in the EDTA group was measured with a non-significant gain of 0.4+/-1.2 mm in
      the control group. Radiographic analysis confirmed these results. There were no
      statistically significant differences in treatment outcome between the group
      treated by root conditioning in combination with flap surgery and conventional
      flap surgery alone.

PMID- 9763326
TI  - Low stimulation of peripheral lymphocytes, following in vitro application of
      Emdogain.
AB  - Fast tissue regeneration after therapeutic manipulations is a central problem of
      periodontology, oral surgery and trauma of the periodontal tissues, including
      bone. Several products, which augment tissue regeneration, have been manufactured
      and assayed in clinical practice with positive results. Emdogain is a recent
      addition in this field, as a tissue-regenerating product. The substance is a
      derivative of amelogenin, obtained from porcine embryonic tissues. At the present
      time, it is not known whether the substance can induce a local (due to the uptake
      of the substance) or systemic immune response. The aim of the present study was
      to evaluate, in vitro, the ability of Emdogain to influence, in vitro, the immune
      system. Peripheral blood lymphocytes, isolated for 10 healthy donors, were
      cultured in the presence of various concentrations of the substance, in order to
      determine the rate of cell proliferation, the expression of surface antigens and
      the production of cytokines and immunoglobulins. Under our experimental
      conditions, Emdogain produced a slight increase of the proliferation of
      lymphocytes, restricted to the CD25 (IL-2 receptor) fraction of the CD4 positive
      T-lymphocytes, and a concomitant decrease of CD19 positive B-lymphocytes. Other
      cell fractions (CD8 positive T-cells, B-cells and NK-cells) were not affected.
      Under our conditions too, immunoglobulin and cytokin (IL-2 and IL-6) production
      was not modified, even after a 3-day application of concentrations much higher
      than those used in clinical practice. Our data suggest that Emdogain slightly
      induce an immune response, restricted to the activated fraction of CD4 T
      lymphocytes in vitro.

PMID- 9763327
TI  - The mucosal attachment at different abutments. An experimental study in dogs.
AB  - The present experiment was performed to examine if the material used in the
      abutment part of an implant system influenced the quality of the mucosal barrier
      that formed following implant installation. 5 beagle dogs were included in the
      study. The mandibular premolars and the 1st, 2nd and 3rd maxillary premolars were
      extracted. Three fixtures of the Branemark System were installed in each
      mandibular quadrant (a total of 6 fixtures per animal). Abutment connection was
      performed after 3 months of healing. In each dog the following types of abutments
      were used: 2 "control abutments" (c.p. titanium), 2 "ceramic abutments" (highly
      sintered Al2O3), 1 "gold abutment", and 1 "short titanium abutment". This "short
      titanium abutment" was provided with an outer structure made of dental porcelain
      fused to gold. Following abutment connection a plaque control program was
      initiated and maintained for 6 months. The animals were sacrificed and perfused
      with a fixative. The mandibles were removed and each implant region was
      dissected, demineralized in EDTA and embedded in EPON. Semithin sections
      representing the mesial, distal, buccal and lingual aspects of the peri-implant
      tissues were produced and subjected to histological examination. The findings
      from the analysis demonstrated that the material used in the abutment portion of
      the implant influenced the location and the quality of the attachment that
      occurred between the periimplant mucosa and the implant. Abutments made of c.p.
      titanium or ceramic allowed the formation of a mucosal attachment which included
      one epithelial and one connective tissue portion that were about 2 mm and 1-1.5
      mm high, respectively. At sites where abutments made of gold alloy or dental
      porcelain were used, no proper attachment formed at the abutment level, but the
      soft tissue margin receded and bone resorption occurred. The abutment fixture
      junction was hereby occasionally exposed and the mucosal barrier became
      established to the fixture portion of the implant. It was suggested that the
      observed differences were the result of varying adhesive properties of the
      materials studied or by variations in their resistance to corrosion.

PMID- 9763328
TI  - A controlled multicenter study of adjunctive use of tetracycline periodontal
      fibers in mandibular class II furcations with persistent bleeding.
AB  - The aim of this randomized single-blind multicenter controlled clinical trial was
      to clinically evaluate the effectiveness of adjunctive local controlled drug
      delivery in the control of bleeding on probing in mandibular class II furcations
      during maintenance care. 127 patients presenting with a class II mandibular
      furcation with bleeding on probing were included in the study. They had been
      previously treated for periodontitis and were participating in supportive care
      programs in periodontal specialty practices. Treatments consisted of scaling and
      root planing with oral hygiene instructions (control) and scaling and root
      planing and oral hygiene combined with local controlled drug delivery with
      tetracycline fibers (test). The following outcomes were evaluated at baseline and
      3 and 6 months after therapy at the furcation site: bleeding on controlled force
      probing (BOP), probing pocket depth (PD) and clinical attachment levels (CAL).
      Levels of oral hygiene and smoking status were also assessed. Both test and
      controls resulted in significant improvements of BOP and PD at 3 and 6 months.
      The test treatment, however, resulted in significantly better improvements: BOP
      decreased by 52% in the control group and by 70% in the test group at 3 months;
      at 6 months, however, the difference was no longer significant. The test
      treatment resulted in a 0.5 mm greater reduction of PD than the control at 3
      months, the improvement was highly significant but its duration did not extend
      until the 6 months evaluation. No differences were observed in terms of changes
      in CAL. These data indicate that addition of tetracycline fibers to mechanical
      therapy alone resulted in improved control of periodontal parameters during
      periodontal maintenance of class II mandibular furcations. Short duration of the
      effect, however, requires further investigations to optimize conservative
      treatment of these challenging defects.

PMID- 9763329
TI  - Evaluation of tetracycline fiber therapy with digital image analysis.
AB  - The aims of the present study were to assess radiographically the effects of
      scaling/root planing combined with antibiotic therapy using tetracycline fibers
      (TCF): (I) on alveolar bone density and linear descriptors and (II) on
      supracrestal soft tissue density. 19 subjects with generalized adult
      periodontitis (with at least 20 teeth present, at least 4 teeth with pockets >4
      mm and bleeding upon controlled force probing) and high cultural counts of
      Porphyromonas gingivalis were recruited from a pool of 57 patients. The full
      mouth treatment group (FT) consisted of 10 patients, who underwent a full mouth
      supra-gingival scaling and prophylaxis treatment and were instructed to rinse 2x
      daily with a 0.1% chlorhexidine solution. 1 week later, tetracycline
      hydrochloride-containing fibers (Actisite periodontal fiber) were applied around
      all teeth. After 7-12 days, the fibers were removed and all teeth were scaled and
      root planed under local anaesthesia. The chlorhexidine rinsing continued for
      another 2 months. In 9 subjects (local treatment group LT), 2 teeth with
      periodontal lesions with pocket probing pepth (PPD) > or =5 mm were treated by
      placement of tetracycline fibers, which remained in place for 7 to 12 days. Upon
      removal of the fibers, scaling and root planing was performed on these 2 teeth,
      while the rest of the dentition remained untreated, and no chlorhexidine rinse
      was applied. 2 of the untreated teeth revealing similar periodontal lesions were
      chosen to represent sites affected by untreated periodontitis (NT). In this
      group, a limited local treatment was performed (2 teeth) with the inherent
      potential for recolonization from the untreated pocket sites. Standardized
      periapical radiographs were obtained from the 4 monitored sites within each
      patient at baseline (before treatment) and 2 and 6 months thereafter. One
      radiograph was exposed in a standard way for bone assessment. The second
      radiograph was underexposed, at about a 1/5 of the original exposure time to
      allow the evaluation of soft tissue. Mean changes in the linear parameters and
      changes in density (CADIA) observed at multiple sites within each patient and
      treatment group were used as the best estimate of treatment outcome. Over the
      observation period of 6 months, a significant difference in bone height changes
      was found between the untreated sites (median loss -0.29 mm) and the sites from
      full-mouth treated patients (median gain 0.24 mm, p=0.008). When comparing the
      baseline to the 6 months radiographs, a loss in bone density was observed for the
      untreated group (median=-2.13 CADIA). Both treatment groups revealed a gain in
      density (median=1.58 and 2.43 CADIA for the locally and the full-mouth treated
      groups, respectively). Differences in density were significant, both between the
      nontreated and locally treated sites (p=0.026) and between the nontreated sites
      and the sites from the full mouth treated patients (p=0.002). The analysis of the
      soft tissues showed a similar pattern of changes in density to those seen in the
      bone defect. At 2 months, there was a tendency for loss in density for the
      nontreated group (median=-0.17 CADIA) that continued over the 6 month period
      (median=-0.31 CADIA). A significant increase in density was observed for the full
      mouth treated sites (median=1.57 and 0.64 CADIA for the 2 and 6 months
      radiographs, respectively). A significant increase was also observed for the
      locally treated group when compared to the untreated sites (median=0.13 and 0.10
      CADIA for the 2 and 6 months radiographs, respectively). Comparing untreated
      sites with full-mouth treated sites, a significant difference was observed for
      CADIA measurements (p<0.001). No significant difference was observed comparing
      locally treated and untreated sites (p=0.24). It was concluded that scaling and
      root planing combined with TCF therapy can result in increased bone density and
      alveolar bone height. Full-mouth treatment seemed to result in more pronounced
      gains compared to local tre

PMID- 9763331
TI  - High levels of soluble intercellular adhesion molecule-1 (ICAM-1) in crevicular
      fluid of periodontitis patients with plaque.
AB  - The intercellular adhesion molecule-1 (ICAM-1) is a membrane-bound molecule
      involved in cell-cell adhesive interactions which is upregulated on inflammatory
      epithelial cells. The levels of soluble ICAM-1 (sICAM-1) shed into the gingival
      crevicular fluid (GCF) were studied in healthy patients and patients with
      gingivitis, adult periodontitis or rapidly progressive periodontitis, using an
      ELISA technique. Clinical parameters including plaque index, gingival index,
      probing depth, and bleeding on probing were recorded following careful sampling
      of GCF with standardised filter strips. In GCF, sICAM-1 levels were higher for
      patients with plaque (p=0.04) and for patients with inflammation (p=0.02), but
      did not correlate with disease classifications. These results suggest that
      elevated GCF sICAM-1 levels may represent increased shedding of this molecule in
      the interstitial fluid as a result of membrane-bound ICAM-1 upregulation on ICAM
      1 gingival-bearing cells in relation with plaque accumulation and inflammation.

PMID- 9763330
TI  - 6-month use of 0.2% delmopinol hydrochloride in comparison with 0.2%
      chlorhexidine digluconate and placebo. (I). Effect on plaque formation and
      gingivitis.
AB  - A double-blind, randomised, 6-month clinical trial with parallel group design in
      149 patients with gingivitis was conducted to study the efficacy and safety of
      delmopinol hydrochloride 2 mg/ml (0.2% w/v, Decapinol Mouthwash) used for partly
      supervised mouthrinsing in comparison with chlorhexidine digluconate 2 mg/ml
      (0.2% w/v, Hibitane Dental, ICI Pharmaceuticals, UK) and placebo as an addition
      to normal oral hygiene. Assessments of efficacy were performed using the plaque
      index and bleeding on probing (BOP). Delmopinol showed 22% lower plaque index
      scores than placebo after 3 months (p<0.01) and 13% lower scores after 6 months.
      The corresponding figures for chlorhexidine were 38% (p<0.001) and 38% (p<0.001)
      after 3 and 6 months, respectively. Bleeding on probing was reduced for
      delmopinol in comparison with placebo by 11% after 3 months and by 18% (p<0.05)
      after 6 months. For chlorhexidine the corresponding figures were 18% (p<0.01) and
      22% (p<0.01) after 3 and 6 months, respectively. While chlorhexidine showed
      greater plaque reduction than delmopinol (p<0.01 at 6 months), no statistically
      significant difference was reached between these two solutions regarding BOP.
      Both active solutions showed an increased amount of dental calculus in comparison
      with placebo. A transient anaesthetic sensation in the oral mucosa and taste
      affection were commonly reported adverse events in both the delmopinol and the
      chlorhexidine groups. The number of patients withdrawn from treatment due to
      adverse events or lack of cooperation was 7 in the chlorhexidine group, 4 in the
      placebo group and 1 in the delmopinol group. The results showed that rinsing with
      either 0.2% delmopinol hydrochloride or 0.2% chlorhexidine digluconate twice
      daily for 60 secs for 6 months results in less plaque formation and gingivitis
      than rinsing with placebo. Mouthrinsing with the 0.2% delmopinol hydrochloride
      solution was well accepted in this study.

PMID- 9763332
TI  - Subgingival microflora and treatment in prepubertal periodontitis associated with
      chronic idiopathic neutropenia.
AB  - Prepubertal periodontitis affects both primary and permanent dentition. The
      purpose of this study was to examine the composition of subgingival microflora of
      the permanent dentition in an 11-year-old Caucasian female, who had premature
      exfoliation of her deciduous teeth on her 5th year of age, and the response of
      this condition to the antibiotic therapy and supportive periodontal care.
      Gingival tissues were highly inflamed and alveolar bone loss was detected
      radiographically. The girl had experienced frequent upper respiratory tract
      infections, tonsilitis and recurrent otitis media. Her mother had history of
      early onset periodontitis associated with chronic idiopathic neutropenia. Blood
      chemistry tests and immunological examinations were also performed. Subgingival
      plaque samples were collected from the proximal sites of permanent molars,
      incisors, canines and maxillary premolars. 27 different microbial species were
      isolated from the subgingival microflora. Among the predominant species were
      Porphyromonas gingivalis (17.6%-7.3%), Prevotella intermedia (12.4%-4.7%),
      Capnocytophaga sputigena (14.4%-10.4%), Capnocytophaga ochracea (13.2%-6.9%) and
      Actinobacillus actinomycetemcomitans (9.3%-5.5%). Periodontal treatment consisted
      of scaling, root planing in conjunction with antibiotic administration of
      Augmentin 312.5 mg and Flagyl 200 mg, each t.i.d. for 10 days. 3 weeks after the
      antibiotic therapy, bacterial samples were collected from the same sites. All the
      periodontal pathogens were recovered in lower levels and A.actinomycetemcomitans
      was almost eliminated in the 3-week period. The evaluation of clinical indices at
      3, 6 and 12 months showed that periodontal treatment in conjunction with
      antibiotics was effective and rapidly followed by marked clinical improvement.
      The microbiological monitoring at 3, 6 and 12 months after antibiotic treatment
      and each time prior to supportive periodontal care, revealed that the periodontal
      pathogens fluctuated in low levels even 12 months after treatment and could be
      maintained at low level by supportive periodontal care at 3-month intervals.

PMID- 9763333
TI  - MRI anatomy of white matter layers around the trigone of the lateral ventricle.
AB  - MRI was obtained in eight normal volunteers and seven patients with brain oedema
      around the trigone. In addition to the conventional sequences, diffusion-weighted
      and intravoxel-incoherent-motion images using motion-proving anteroposterior
      and/or lateral direction gradients were obtained to show the white matter
      pathways better. Coronal proton-density-weighted images showed three thin
      relatively high-intensity layers in addition to the tapetum and the internal and
      external sagittal strata. Although they have not been confirmed anatomically, the
      thin layer between the internal and the external sagittal strata was corroborated
      by diffusion-weighted and intravoxel-incoherent-motion images, and by
      characteristics of the spread of oedema into the sagittal stratum. We propose
      that this layer be named the central sagittal lamina. The other two layers medial
      and lateral to the sagittal stratum were outside, but in contact with the medial
      and lateral parts of the sagittal stratum, respectively. We provisionally named
      them medial and lateral sagittal laminae; they were not evident on any other
      images. The low-intensity layer on T2-weighting was the internal sagittal
      stratum. The optic radiation, comprising the external sagittal stratum, appeared
      as an intermediate to slightly high-intensity layer on T2-weighted images and a
      low-intensity layer on T1-weighted images as did the corticospinal tract in the
      posterior internal capsule.

PMID- 9763334
TI  - Fast fluid-attenuated inversion-recovery imaging: first experience with a 3D
      version in epilepsy.
AB  - We developed a 3D version of fast fluid-attenuated inversion-recovery imaging
      (FLAIR) which provides images with a slice thickness of 1.5 mm. We present our
      initial experience with 3D fast FLAIR in patients with epilepsy. We compared 3D
      fast FLAIR (slice thickness 1.5 mm), 2D fast FLAIR (slice thickness 5 mm) and a
      3D spoiled GRASS (IRSPGR) sequence (slice thickness 1.5 mm) in 10 patients with
      lesional epilepsy (head injury 1, hippocampal sclerosis 2, low-grade glioma 2,
      dysembryoplastic neuroepithelial tumour 2, polymicrogyria 1, perinatal infarct 1
      and presumed thrombosed aneurysm 1). Both 2D and 3D fast FLAIR sequences yielded
      higher conspicuity for lesions than the T1-weighted IRSPGR sequence, except in
      the patient with polymicrogyria. The extent of the lesion, in particular that of
      low-grade tumours, was best assessed on 3D fast FLAIR images. 3D fast FLAIR may
      be a useful additional tool especially for imaging low-grade tumours.

PMID- 9763335
TI  - Transcranial duplex sonography of middle cerebral artery stenosis: a comparison
      of colour-coding techniques--frequency- or power-based Doppler and contrast
      enhancement.
AB  - The main limitation of transcranial colour-coded duplex sonography (TCCD) is the
      inadequate acoustic window, which prevents transtemporal identification of the
      basal cerebral arteries in up to 30% of cases, especially in the elderly. TCCD
      with different colour-coding techniques, including frequency-based colour-flow
      (CFD) or power (PD) Doppler sonography, used alone or in combination with
      contrast media, were used in 23 patients with middle cerebral artery (MCA)
      stenosis. In 10 patients a contrast medium (400 mg/ml SHU 508 A) was administered
      because of inadequate colour-coded visualisation with TCCD. The data were
      compared with angiographic methods. Digital subtraction angiography (DSA)
      revealed 2 low-grade, 11 middle-grade and 10 high-grade stenoses in the M1
      segment. With TCCD, we found a 7.7% higher blood flow velocity (systolic peak
      velocity) than with transcranial duplex sonography without colour-coding because
      of visual angle correction and a 20% higher systolic peak velocity using contrast
      enhancement. CFD did not differ from PD in identification of low- and middle
      grade MCA stenoses, but PD alone revealed two more cases of high-grade stenosis
      than CFD. The contrast medium increased diagnostic confidence in 8 of 10 cases.
      Only 2 of 23 MCA stenoses (9%) could not be shown using TCCD.

PMID- 9763337
TI  - Assessment of T2- and T1-weighted MRI brain lesion load in patients with
      subcortical vascular encephalopathy.
AB  - Previous cross-sectional studies in patients with subcortical vascular
      encephalopathy (SVE) have shown little or no correlation between brain lesion
      load and clinical disability, which could be due to the low specificity of T2
      weighted MRI. Recent studies have indicated that T1-weighted MRI may be more
      specific than T2-weighted MRI for severe tissue destruction. We studied 37
      patients with a diagnosis of SVE and 11 normal controls with standardised T1- and
      T2-weighted MRI. All patients underwent detailed clinical assessment including a
      neuropsychological test battery and computerised gait analysis. Both the T2- and
      T1-weighted total MRI lesion loads different between patients and controls
      different, particularly T1. The ratio of T2-/T1-weighted lesion load was lower in
      controls than in patients. There was no overall correlation of T1- or T2-weighted
      lesion load with clinical disability, but group comparison of patients with
      severe and mild clinical deficits showed different lesion loads. We suggest that
      T1- and T2-weighted MRI lesion loads demonstrate relevant structural abnormality
      in patients with SVE.

PMID- 9763336
TI  - MRI assessment of cerebral blood volume in patients with brain infarcts.
AB  - MRI perfusion studies have focussed mainly on acute ischaemia and
      characterisation in ischaemia. Our purpose was to analyse regional brain
      haemodynamic information in acute, subacute, and chronic ischaemia. We performed
      16 examinations of 11 patients on a 1.5 T MR images. Conventional and dynamic
      contrast-enhanced imaging were employed in all examinations. For the dynamic
      susceptibility sequences, a bolus (0.2 mmol/kg) of gadopentetate dimeglumine was
      injected. Reconstructed regional relative cerebral blood volume (rCBV) maps,
      bolus maps, and conventional images were analysed by consensus reading. In all
      examinations decreases in rCBV were observed in the lesions. The distribution of
      regional rCBV in lesions was heterogeneous. The rCBV of the periphery of the
      lesions was higher than that at their center. There was a correlation between the
      time since onset and abnormalities on the rCBV map and T2-weighted images (T2WI).
      In the early stage of acute stroke, the abnormalities tended to be larger on the
      rCBV than on T2WI. Many patterns of bolus passage were observed in ischaemic
      regions. rCBV maps provide additional haemodynamic information in patients with
      brain infarcts.

PMID- 9763338
TI  - MRI of germinomas arising from the basal ganglia and thalamus.
AB  - We reviewed the MRI findings of germinomas originating from the basal ganglia,
      thalamus or deep white matter in 13 patients with 14 germinomas, excluding those
      in the suprasellar or pineal regions. Ten cases were confirmed as germinomas by
      stereotaxic biopsy, three by partial and one by total removal of the tumour.
      Analysis was focussed on the location and the signal characteristic of the
      tumour, haemorrhage, cysts within the tumour and any other associated findings.
      Thirteen of the tumours were in the basal ganglia and one in the thalamus.
      Haemorrhage was observed in seven patients, while twelve showed multiple cysts.
      Associated ipsilateral cerebral hemiatrophy was seen in three patients. The
      signal intensity of the parenchymal germinomas was heterogeneous on T1- and T2
      weighted images due to haemorrhage, cysts and solid portions. We also report the
      MRI findings of germinomas in an early stage in two patients.

PMID- 9763339
TI  - Meningeal involvement in Behcet's disease: MRI.
AB  - Behcet's disease is a multisystem disease that involves the central nervous
      system up to half of cases. Presentation with neurologic symptoms occurs in 5% of
      cases and cerebral venous thrombosis is one of its major manifestations. A
      feature not previously reported is progressive meningeal thickening with
      involvement of both optic nerves. We report a patient with cerebral venous
      thrombosis, meningeal thickening and contrast enhancement on MRI. This patient
      had two other unusual features: positive antineutrophil cytoplasmic antibodies
      and later development of central diabetes insipidus.

PMID- 9763340
TI  - MRI in a patient with congenital agammaglobulinaemia.
AB  - MRI in a 17-year-old boy with known congenital agammaglobulinaemia (CA)
      demonstrated signs of chronic leptomeningeal inflammation with thickened,
      enhancing meninges. Furthermore, high signal was found symmetrically on T2
      weighted images in the frontal and parietal white matter. The patient presented
      with severe general brain dysfunction and recent cerebellar ataxia. Extensive
      investigation did not reveal a causal agent. This case shows that MRI can be
      helpful in establishing the presence of pathological changes in cases where
      laboratory results are negative.

PMID- 9763341
TI  - MRI in chronic toluene abuse: low signal in the cerebral cortex on T2-weighted
      images.
AB  - MRI may be helpful in showing brain toxicity associated with chronic toluene
      inhalation. We report clinical and MRI findings over 3 years in a man with
      gradual neurologic decline secondary to toluene abuse. Cerebral atrophy most
      prominently involved the corpus callosum and cerebellar vermis. On T2-weighted
      images, loss of gray-white matter contrast, diffuse supratentorial white matter
      high-signal lesions, and low signal in the basal ganglia and midbrain were seen.
      In addition, MRI showed abnormal labor cortical low signal on T2-weighted images,
      most prominent in the primary motor and visual cortex. This cortical T2
      shortening, not previously described in this condition, may reflect iron
      deposition.

PMID- 9763342
TI  - Intraventricular B-cell lymphoma from the breast.
AB  - We report an unusual case of massive intraventricular spread of B-cell lymphoma
      of the breast, presenting with rapidly progressive ataxia and impaired cognition
      with need for ventriculostomy. Rapid resolution followed intravenous
      dexamethasone and radiation therapy.

PMID- 9763343
TI  - Sacral haemangioma as a cause of coccydynia.
AB  - We report a 55-year-old woman with coccydynia due to a sacral mass. The
      histological diagnosis was haemangioma. The MRI findings and the unusual location
      of this lesion are discussed.

PMID- 9763344
TI  - Case report: glomus tumour of the nasal cavity and paranasal sinuses.
AB  - Glomus tumours are relatively rare in the head and neck. We present a glomus
      tumour of the nasal cavity and paranasal sinuses in a 55-year-old man and
      describe the CT appearances of this tumour and its histopathology.

PMID- 9763345
TI  - Effects of systemic heparinization on the thrombogenicity of hydrophilic and
      nonhydrophilic catheters in a swine model.
AB  - We assessed the effect of systemic heparinization on the in-vivo thrombogenicity
      of various micro- and guiding catheters in a swine model. Microcatheters were
      placed through 6-F guiding catheters into the common carotid arteries of swine
      for 30-min (short-term) and 90-min (medium-term) periods, with and without
      systemic heparinization. At the end of the placement period the microcatheters
      were retracted through the guiding catheters and fixed for scanning electron
      microscopy (SEM). Guiding catheters were harvested after 5 h placement, with and
      without systemic heparinization, by retraction through 8-F sheaths and fixed for
      SEM. The surfaces of both hydrophilic and nonhydrophilic microcatheters all
      demonstrated more accumulation of debris during placement without than with
      systemic heparinization. The difference was primarily in the amount of fibrillary
      material on the catheter surface. The guiding catheters also demonstrated
      increased debris accumulation without systemic heparinization. This suggests
      that, even when using relatively nonthrombogenic catheters, systemic
      heparinization is indicated during cerebral angiography.

PMID- 9763346
TI  - Magnetic resonance angiography in patients with acute stroke treated by local
      thrombolysis.
AB  - Although magnetic resonance angiography (MRA) is accepted for showing chronic
      intracranial stenotic or occlusive lesions, the method has not been practically
      examined in patients with acute cerebral ischaemia. We carried out three
      dimensional time-of-flight MRA in six patients with acute ischaemia treated by
      local thrombolysis, and compared the findings with those of digital subtraction
      angiography (DSA). In all patients, MRA before thrombolysis clearly demonstrated
      the occluded arteries, which corresponded precisely to those shown by DSA. In
      four patients with complete recanalisation of the occluded vessels after
      thrombolysis, the recanalisation could be demonstrated by postoperative MRA. In
      one patient with reocclusion of the recanalised artery, repeat MRA also
      demonstrated the reocclusion, confirmed by DSA. These results suggest that MRA
      may be helpful for noninvasive investigation before and after thrombolysis.

PMID- 9763347
TI  - Neuroradiological practices in Europe: Working ESNR Committee on
      Neuroradiological Practices in Neuroradiology. European Society of
      Neuroradiology.
AB  - In order to achieve an overview of neuroradiology in Europe a questionnaire was
      sent to all ESNR National Delegates. The answers received were submitted to a
      data-based analysis, leading to the conclusion that neuroradiology is an
      expanding discipline among neurological sciences.

PMID- 9763348
TI  - Laboratory diagnosis of hereditary thrombophilia.
AB  - Genetic defects of antithrombin (AT) or one of the components of the protein C
      pathway are associated with hereditary thrombophilia. Laboratory assays are
      currently available to diagnose and type hereditary thrombophilia due to
      deficiency or dysfunction of one of the anticoagulant factors antithrombin (AT),
      protein C (PC) and protein S (PS), and APC resistance without the need of DNA
      analysis. There are no functional tests for the prothrombin mutant G20210A and
      thrombomodulin mutations, which can be diagnosed by a PCR-based test or by gene
      analysis, respectively. Hereditary AT deficiency is classified in a quantitative
      type I and three functional type II deficiencies affecting the reactive site
      (RS), heparin binding site (HBS), or pleiomorphic site of the AT protein. All
      four types of hereditary AT deficiencies can be diagnosed by a heparin cofactor
      assay and one immune assay in combination with crossed immunoelectrophoresis of
      the AT protein. The combination of an enzyme-linked immunoadsorbent assay (ELISA)
      and a functional Protac-APTT-based assay for PC will detect quantitative type I
      and dysfunctional type II PC deficiencies. There is a significant overlap in PC
      antigen and functional levels between heterozygotes of PC deficiency and normals
      leaving a gray zone of uncertainty in differentiating congenital PC deficiency
      and normal individuals. Accurate diagnosis of hereditary PS deficiency should be
      a combination of tests aimed to measure free PS activity and antigen and total PS
      antigen levels. APTT-, Xa-, and RVVT-based APC-resistance tests, when test
      plasmas are diluted in factor V deficient plasma, have increased in sensitivity
      and specificity to 100% for the discrimination of normal individuals from
      heterozygotes and homozygotes for factor V Leiden. The RVVT-based APC-resistance
      test provides better separation of factor V Leiden and normals in the various
      clinical settings, lupus anticoagulant in particular. The modified APC-resistance
      tests also claim a separation between heterozygotes and homozygotes for factor V
      Leiden in the normal population, asymptomatic subjects, and thrombosis patients.
      Below a certain cut-off level, a minor overlap of normalized APC ratios between
      heterozygotes and homozygotes for factor V Leiden of thrombosis patients has been
      shown in one study, which still points to the need to perform the more time
      consuming and expensive DNA test to identify heterozygotes from the more
      clinically significant homozygotes. The prothrombin-based APC-resistance test,
      which measures thrombin activated factor Va in highly diluted test plasma,
      appears to be the most sensitive and specific of all APC-resistance tests and
      separates normal individuals from heterozygotes and heterozygotes from
      homozygotes for factor V Leiden without the need of confirmation by a DNA test.

PMID- 9763349
TI  - Screening test for thrombophilic patients: which tests, for which patient, by
      whom, when, and why?
AB  - In the past two decades, several mechanisms leading to thrombophilia have been
      elucidated, and corresponding laboratory tests developed. At a time of financial
      constraints, it is crucial to distinguish between the tests of proven value
      (which can modify the therapeutic attitude toward the patient and/or his family)
      from those of unproven value. We have listed in the first category determination
      or measurement of factor V Leiden, factor II G20210A, antithrombin, protein C,
      protein S, as well as antiphospholipid antibodies and hyperhomocysteinemia. A
      combined clinical and laboratory approach taking into account the history of the
      patient and his family, the prevalence of the defects, and also the accuracy of
      the tests should allow tailoring a laboratory testing program to each individual
      patient. It is essential to keep in mind that the more difficult task is not to
      perform the tests, but to consider who will benefit from testing both for
      prevention and therapy of venous thromboembolism. The present review provides
      answers to some of these issues. These answers should, however, be considered as
      provisional because new findings and study results will certainly modify them in
      the future.

PMID- 9763350
TI  - Molecular biology and pathophysiology of APC resistance: current insights and
      clinical implications.
AB  - APC resistance is often associated with the occurrence of a single point mutation
      in factor V (factor VLeiden) at a predominant cleavage site for the natural
      anticoagulant, activated protein C (APC). In this article we will discuss the
      effects of this mutation (Arg506-->Gln) on the down-regulation of factor Va
      cofactor activity and on thrombin formation by APC in model systems and in
      plasma. Our studies on the effects of APC on thrombin formation in plasma
      resulted in the development of a new method for the screening of APC resistance
      that is based on measurement of the effect of APC on the endogenous thrombin
      potential (the time integral of thrombin generated in clotting plasma). It
      appeared that sensitivities for APC determined via this method were considerably
      affected by the use of oral contraceptives (OC) and that women who use OC become
      acquired APC resistant. The fact that acquired APC resistance in women who use
      third-generation OC was more pronounced than in users of second-generation OC may
      explain the further increased risk for venous thrombosis associated with the use
      of third-generation OC.

PMID- 9763351
TI  - The anticoagulant potential of the protein C system in hereditary and acquired
      thrombophilia: pathomechanisms and new tools for assessing its clinical
      relevance.
AB  - The diagnosis of the procoagulant system is routinely based on activated partial
      thromboplastin time (APTT) and PT results indicating only a bleeding tendency.
      Routine screening tests for thrombophilia providing an objective measure of the
      anticoagulant potential of the blood are still lacking. Only antithrombin is
      determined quite frequently. The recent findings of activated protein C (APC)
      resistance have demonstrated the importance of the PC anticoagulant system in
      inherited thrombophilia. A vast body of evidence from in vitro and animal
      experiments as well as from recent clinical studies is presented revealing that
      the PC system potential plays a major role in maintaining the hemostatic balance
      at a variety of clinical conditions. It is suggested that acquired defects in the
      PC system are an underestimated cause for clinically induced venous thrombosis.
      New screening assays for the PC system potential are presented, which already
      indicate quite well congenital as well as acquired interferences of the PC system
      potential.

PMID- 9763352
TI  - A protein C pathway (PCP) screening test for the detection of APC resistance and
      protein C or S deficiencies.
AB  - A new automated method for screening defects in the Protein C Pathway (PCP) was
      evaluated. The "PCP test" is based on a phospholipid-rich Russells viper venom
      reagent, insensitive to heparin and lupus anticoagulants. To minimize
      interference from other clotting variables, ratios of the clotting time with and
      without the addition of a protein C activator were usually determined. Plasma
      samples from healthy volunteers, patients untreated or on oral anticoagulants,
      patients with factor V Leiden with and without treatment, and patients with
      protein C and/or S deficiencies were tested. Mixing patient plasmas 1:1 with
      individual plasmas deficient in factor V, protein C or S was evaluated for
      identifying the nature of defects by shortening the screening test. The PCP test
      was found to be sensitive to APC resistance due to factor V Leiden and by mixing
      with factor V deficient plasma was also useful despite the effects of oral
      anticoagulants. Results in the group of patients with previous low protein C or S
      levels suggest that the method has a better sensitivity to protein C than to
      protein S deficiency. The automated test was simple to use and gave a between-run
      coefficient of variation below 3% on normal plasmas.

PMID- 9763353
TI  - Factor V:Q506 mutation-resistance to activated protein C (APC): clinical
      implications with respect to family screening.
AB  - Resistance to activated protein C (APC), which is almost exclusively caused by a
      point mutation in the factor V gene (FV:Q506 mutation or FV Leiden) is a recently
      discovered, prevalent risk factor for the occurrence of venous thromboembolism.
      It is unknown whether relatives of known patients with this mutation should be
      screened for the presence of the mutation and what the consequences for
      asymptomatic carriers would be. This paper addresses the possible benefits and
      disadvantages of family screening of patients with venous thromboembolism who
      carry the mutation. Possible prophylactic strategies are discussed and weighed on
      the basis of estimated incidence rates of venous thromboembolism that are deduced
      from known relative risks and available population studies.

PMID- 9763354
TI  - Epidemiology of factor V Leiden: clinical implications.
AB  - Inherited resistance to activated protein C (APC) has been recently recognized as
      a novel cause underlying venous thrombophilia. In most cases APC resistance is
      due to a single point mutation in the factor V gene leading to a replacement of
      Arg506 with Gln (factor V Leiden). Factor V Leiden allele is present in about 5%
      of the Caucasian individuals (Europeans, Jews, Israeli Arabs, and Indians) and is
      virtually absent in Africans, Asians, and races with Asian ancestry such as
      Amerindians, Eskimos, and Polynesians; this suggests a single origin of the
      mutation, which has been proven by haplotype analysis. A low prevalence of the
      mutation (1%) was noticed in African-Americans for recent racial admixture.
      Factor V Leiden presents not a major role as risk factor for arterial thrombosis,
      while it is present in 18% of Caucasian patients with venous thrombosis. This
      high incidence prevalence mirrors the incidence in the corresponding general
      populations and can be even higher in some areas according to the ethnic
      background. Conversely, factor V Leiden is usually not found in non-Caucasian
      thrombotic patients; this could give reason of the lower incidence of venous
      thrombotic disease in Africa and Asia in comparison with Europe. Therefore,
      screening for factor V Leiden is suggested for all Caucasian individuals with
      previous venous thrombosis; inclusion criteria for the screening should not be
      stringent because clinical manifestations associated with the mutant genotype can
      be also mild or secondary to circumstantial risk factors or manifesting at
      advanced age. Factor V Leiden can act also as concurrent risk factor in
      individuals with deficiency of natural inhibitors or mild hyperhomocysteinemia.
      So far, screening for the mutation in individuals with no history of thrombosis
      is recommended only for relatives of proband patients identified as carriers; the
      available data do not justify indiscriminate screening before risk situations
      such as oral contraceptives intake, pregnancy, or high-risk surgery.

PMID- 9763355
TI  - Hyperhomocysteinemia and atherothrombotic disease.
AB  - Hyperhomocysteinemia is an independent risk factor for atherothrombotic disease.
      The mechanism by which homocysteine induces atherosclerosis and thrombosis is not
      fully understood. Data on arterial histology in humans with homocystinuria and
      mild hyperhomocysteinemia are limited. In vitro studies as well as studies in
      animals and humans indicate that hyperhomocysteinemia induces dysfunction of the
      vascular endothelium, with loss of endothelium-dependent vasodilation and
      endothelial antithrombotic properties, and proliferation of vascular smooth
      muscle cells, which are key processes in current models of atherogenesis and
      thrombosis. One of the hypotheses is that homocysteine can lead to cellular
      dysfunction through a mechanism involving oxidative damage but future studies in
      humans are needed to confirm this. Studies in hyperhomocysteinemic vascular
      patients have shown that endothelial antithrombotic properties appear to be more
      severely impaired than in similar patients with normohomocysteinemia.
      Furthermore, impaired endothelium-dependent vasodilation has been observed in
      clinically healthy hyperhomocysteinemic subjects in whom no abnormalities were
      found in endothelial antithrombotic properties. Future studies involving
      homocysteine-lowering treatment in hyperhomocysteinemic patients with vascular
      disease and in clinically healthy hyperhomocysteinemic subjects are necessary to
      investigate the mechanisms by which homocysteine causes atherothrombotic
      disorders in humans.

PMID- 9763356
TI  - Hyperhomocysteinemia and venous thrombosis.
AB  - In recent years hyperhomocysteinemia has been established as a new risk factor
      for neural tube defects, arterial cardiovascular disease, and venous thrombosis.
      Concerning vascular problems, it first became clear that hyperhomocysteinemia
      might be (though not proven) a risk factor for arterial disease as observed in
      case-control studies, as well as in prospective analysis. More recently, the
      subject of hyperhomocysteinemia and venous thrombosis has received much
      attention. In this article, we discuss the issue of hyperhomocysteinemia, in
      general, the known causes of hyperhomocysteinemia and the association with venous
      thrombosis. Special attention is given to the value of the methionine loading
      test to diagnose hyperhomocysteinemia. An association of venous thrombosis and
      hyperhomocysteinemia has now been documented in several case control studies, but
      only in one prospective analysis. Thus far, there is limited evidence for a
      causal relationship for mild hyperhomocysteinemia in venous thrombosis. Briefly,
      the possible mechanisms of how hyperhomocysteinemia can lead to venous thrombosis
      are discussed. The article ends with therapeutic options to treat
      hyperhomocysteinemia (hyperhomocysteinemia can easily be treated with vitamins)
      and the description of a study that is presently being undertaken in an
      international multicenter design. This placebo-controlled study might resolve the
      question of whether lowering of homocysteine levels is of any clinical relevance
      in preventing recurrent venous thrombosis.

PMID- 9763357
TI  - Rapid D-dimer assays to exclude deep venous thrombosis and pulmonary embolism:
      current status and new developments.
AB  - Studies measuring the fibrin degradation product D-Dimer (DD) using enzyme-linked
      immunosorbent assays (ELISA) in patients suspected of deep venous thrombosis
      (DVT) or pulmonary embolism (PE) suggest that it is possible to exclude DVT/PE
      when the DD level is below a certain cut-off value. However, ELISA methods are
      time-consuming, bare high costs, and are only available in experienced
      laboratories. For this reason several rapid and less costly DD assays have been
      recently developed. This article reviews the current literature about rapid latex
      and ELISA DD assays in the diagnostic approach of DVT and PE. Two new latex
      assays seem suitable in clinical practice. The most extensively studied assay is
      the so-called SimpliRed DD, an autologous red cell agglutination test that can be
      performed on fresh whole blood. For DVT a sensitivity (Sens) and a negative
      predictive value (NPV) of 89-100% and 95-100%, respectively, have been reported,
      for PE 94-100% and 98-100%, respectively. The second test, Tinaquant, is a
      quantitative latex assay. Sens and NPV for DVT of 99% and 93% have been reported
      in one study. Two rapid ELISA assays have been investigated. The most extensively
      studied is the VIDAS DD assay, a fully automated quantitative ELISA method. Sens
      and NPV of 94-100% and 92-100% for DVT and both 100% for PE have been reported.
      For the other rapid ELISA, Instant IA DD, Sens and NPV of 92-93% and 76-77% have
      been reported for DVT. The last one is a qualitative assay giving only positive
      or negative results. These results show that low concentrations of plasma DD
      measured by especially SimpliRed or VIDAS DD, might be used to reliably rule out
      DVT or PE in clinically suspected patients. Tinaquant seems promising and has to
      be evaluated further. As for standard ELISA, increased DD concentrations are of
      no use because of the low specificity of the assays. Future studies should assess
      the clinical usefulness of both assays in management trials under routine
      conditions, in the frame of clinical decision-making diagnostic processes to
      prove that withholding further noninvasive testing and/or anticoagulants in
      patients with a low or negative DD is safe. Strategies to identify patients with
      false-negative results should be developed.

PMID- 9763358
TI  - Rational diagnosis of deep vein thrombosis (RADIA DVT) in symptomatic outpatients
      with suspected DVT: simplification and improvement of decision rule analysis for
      the exclusion and diagnosis of DVT by the combined use of a simple clinical
      model, a rapid sensitive D-dimer test and compression ultrasonography (CUS).
AB  - The diagnosis of deep vein thrombosis (DVT) in outpatients is difficult to
      establish. The classical clinical signs of DVT are unspecific and found in
      several other conditions besides DVT. Therefore, these patients are subjected to
      elaborate, expensive invasive or noninvasive procedures that actually confirm DVT
      in only 20-30% of patients in this setting. A prospective management decision
      study, based on a pretest clinical probability (PCP) estimation, compression
      ultrasonography (CUS), and a rapid enzyme-linked immunoadsorbent assay (ELISA) D
      dimer test, is proposed. The PCP model of Wells allows for reasonably accurate
      classification of patients into low, moderate and high probability for suffering
      DVT. Combined with CUS, high predictability is achieved. The D-dimer assays
      presently available can be rapidly performed and are accurate to a high degree,
      especially in ruling out DVT. It is proposed to establish a "Rational Diagnosis
      of Deep Vein Thrombosis (RADIA DVT)" model to be tested in a large number of
      patients with suspected DVT. This model would be less expensive to perform and
      likely yield a highly accurate diagnosis on the basis of which anticoagulant
      therapy could be initiated or withheld.

PMID- 9763359
TI  - The place of D-dimer testing in an integrated approach of patients suspected of
      pulmonary embolism.
AB  - When a patient is suspected of having pulmonary embolism (PE), the first
      procedure performed in most institutions is lung scintigraphy. Here we propose an
      alternative diagnostic strategy based on the following sequential combination of
      procedures: clinical assessment, D-dimer measurement, ultrasonography of lower
      limbs, and lung scan. This integrated approach may rule out PE in the majority of
      outpatients suspected of PE and permits district hospitals without lung-scan
      facilities to manage approximately 50% of outpatients without referral. D-dimer
      alone will exclude PE in about 30% of patients at low cost. This stepwise
      strategy is especially useful because only 20-35% of patients suspected of PE
      really have the disease. Thus, in the majority of patients, ruling out the
      disease has replaced ruling in the disease.

PMID- 9763360
TI  - Rational diagnosis of pulmonary embolism (RADIA PE) in symptomatic outpatients
      with suspected PE: an improved strategy to exclude or diagnose venous
      thromboembolism by the sequential use of a clinical model, rapid ELISA D-dimer
      test, perfusion lung scan, ultrasonography, spiral CT, and pulmonary angiography.
AB  - A prospective management decision analysis for the exclusion and diagnosis of
      pulmonary embolism (PE) based on pre-test clinical probability (PCP) estimation
      for PE, a rapid ELISA D-dimer test, perfusion lungscan (P-scan), CUS, spiral CT,
      and pulmonary angiography is proposed. The modified PCP model for PE of Wells et
      al. allows reasonably accurate classification of patients with no, low, moderate,
      and high probability for PE. The combined rational use of the evidence-based
      noninvasive imaging techniques P-scan, CUS, and spiral CT with the rapid ELISA D
      dimer test and PCP will reduce the need for invasive pulmonary angiography to
      perhaps 10 to 15% of patients, who initially presented with suspected PE. A
      Rational Diagnosis of Pulmonary Embolism (RADIA PE) model is proposed for testing
      in a large multicenter study of patients with suspected PE.

PMID- 9763361
TI  - Of muscles, merosin, and migration.

PMID- 9763362
TI  - . . . But will it play in Peoria?

PMID- 9763363
TI  - Detection of perineural spread: fat is a friend.

PMID- 9763364
TI  - No drug is benign.

PMID- 9763365
TI  - Intracranial angioplasty: a little science enters into the mix.

PMID- 9763366
TI  - Neuroimaging manifestations and classification of congenital muscular
      dystrophies.
AB  - BACKGROUND AND PURPOSE: Recent work has shown that up to 50% of patients with
      congenital muscular dystrophies (CMDs) have abnormalities of the brain that can
      be detected by brain MR imaging. We attempted to determine whether brain MR
      imaging is useful for the diagnosis and classification of patients with CMDs.
      METHODS: The brain MR studies of 12 patients with biopsy-proved CMDs were
      reviewed retrospectively. Using information available in the literature regarding
      associated brain anomalies as a guide, an attempt was made to classify the
      patients in terms of "pure" CMD, CMD with occipital agyria, Fukuyama CMD, muscle
      eye-brain disease, or Walker-Warburg syndrome. RESULTS: All the patients were
      easily classified into one of four groups: pure CMD (four patients), Fukuyama CMD
      (four patients), muscle-eye-brain disease (two patients), or Walker-Warburg
      syndrome (two patients). Patients with pure CMD had diffuse central cerebral
      hypomyelination with mild pontine and cerebellar hypoplasia. Patients with
      Fukuyama CMD had diffuse central cerebral hypomyelination, cerebellar
      polymicrogyria (with or without cysts), frontal polymicrogyria, a variable degree
      of hypoplasia of the pons and cerebellar vermis, and a variable occipital
      cobblestone cortex. Patients with muscle-eye-brain disease had cerebellar
      polymicrogyria (with or without cysts), absence of the septum pellucidum, diffuse
      cerebral cortical dysplasia, pontine and cerebellar vermian hypoplasia, patchy
      hypomyelination, and variable callosal hypogenesis and hydrocephalus. Patients
      with Walker-Warburg syndrome had diffuse cerebral cobblestone cortex, absence of
      cerebral and cerebellar myelin, cerebellar polymicrogyria (with or without
      cysts), pontine and cerebellar vermal hypoplasia, hydrocephalus, and variable
      callosal hypogenesis. CONCLUSION: MR imaging shows distinctive brain anomalies
      that allows patients with CMD to be classified into four distinct groups that are
      consistent with known disorders.

PMID- 9763367
TI  - MR of the normal neonatal brain: assessment of deep structures.
AB  - BACKGROUND AND PURPOSE: MR imaging is a powerful tool for studying the anatomy of
      and the developmental changes that occur in the brain. The purpose of this
      project was to determine which structures can be distinguished on standard spin
      echo MR sequences of a normal neonatal brain and with what frequency they can be
      identified. METHODS: The T1- and T2-weighted spin-echo MR images of 12 term
      neonates, all of whom had normal neonatal courses and were neurologically and
      developmentally normal at age 12 months, were reviewed retrospectively. All
      structures that differed in signal intensity from unmyelinated gray matter and
      unmyelinated white matter were recorded. RESULTS: In general, myelinated gray
      matter structures, such as cranial nerve nuclei and other nuclei of the brain
      stem and deep cerebrum, were the structures best seen on T2-weighted images. Most
      of these nuclei were seen in 75% to 100% of our subjects on T2-weighted images.
      They were seen less well on T1-weighted images. Myelinated white matter
      structures, particularly axonal tracts, were the structures best seen on T1
      weighted images. The medial and lateral lemnisci, median longitudinal fasciculus,
      optic tracts, superior and inferior cerebellar peduncles, and the posterior limbs
      of the internal capsules were seen in 75% to 100% of our subjects on T1-weighted
      images. Except for the posterior limbs of the internal capsules, these structures
      were seen less well on T2-weighted images. CONCLUSION: A large number of small
      structures, such as the nuclei of the brain stem and deep cerebral nuclei, can be
      routinely identified on standard spin-echo MR imaging sequences. A knowledge of
      these structures is essential to proper interpretation of imaging studies in
      neonates and infants.

PMID- 9763368
TI  - Contrast-enhanced three-dimensional fast imaging with steady-state precession
      (FISP) MR angiography of supraaortic vessels: preliminary results.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to assess the effectiveness
      of contrast-enhanced fast three-dimensional (3D) MR angiography in depicting both
      the carotid and vertebral arteries in their cervical portions and to compare MR
      angiography with conventional angiography for the evaluation of arteriosclerotic
      disease. METHODS: Twenty-seven patients with ischemic cerebral events in the
      anterior (n = 18) and posterior (n = 9) circulation underwent contrast-enhanced
      3D MR angiography in the coronal plane. MR angiograms were examined in a blinded
      fashion by two observers independently. Stenosis was classified according to the
      appearance of the residual lumen (no stenosis, mild stenosis, moderate stenosis,
      severe stenosis, occlusion). Conventional angiography was used as the standard of
      reference. RESULTS: Proximal great vessels and carotid siphons were not
      assessable on MR angiograms in 35% of cases owing to limited coverage. All
      cervical and petrous segments of the internal carotid arteries (ICAs) and 93% of
      the extracranial vertebral arteries were assessable. Flow-related artifacts were
      observed in seven cases of severe stenosis, including three with signal void at
      the site of narrowing and four with signal loss in the distal ICA. Interobserver
      agreement was good and significant. Overall agreement between 3D MR angiography
      and conventional angiography was good for the anterior and posterior circulations
      despite a tendency toward overestimation of stenoses on MR angiograms. Clinically
      relevant stenoses and occlusions were correctly identified on 3D MR angiograms,
      providing good sensitivity and specificity. CONCLUSION: Contrast-enhanced 3D MR
      angiography is a promising tool for assessing arteriosclerotic lesions of
      supraaortic vessels. Further studies with larger groups are required to determine
      its value for patient care.

PMID- 9763369
TI  - Abnormal origin of the vertebral artery from the common carotid artery.
AB  - An abnormal origin of the vertebral artery from the common carotid artery (VA-CC)
      may occur on the right or left side with different embryonic mechanisms. We
      describe a patient with a double developmental anomaly, a right VA-CC and a right
      aortic arch. The rotation of the aortic arch caused a "twist" of the embryonic
      mechanisms of VA-CC and misdirected the differential diagnosis of the embryonic
      mechanisms at first glance. We discuss the pivotal points in differentiating the
      embryonic mechanisms of VA-CC.

PMID- 9763370
TI  - Imaging of perineural tumor spread from palatal carcinoma.
AB  - Carcinomas of the hard or soft palate are known to spread perineurally along
      palatine branches of the maxillary nerve. Imaging of perineural tumor spread from
      the palate has been underemphasized in the imaging literature. We report the
      findings from eight patients in whom spread from primary cancers of the palate
      was seen along the palatine nerves. Indications of perineural spread include
      enlargement or excessive enhancement of a nerve, or abnormal density/signal
      intensity, enhancement, or widening of the pterygopalatine fossa, cavernous
      sinus, or Meckel's cave.

PMID- 9763371
TI  - Osseous anatomy of the pterygopalatine fossa.

PMID- 9763372
TI  - Sudden hearing loss: frequency of abnormal findings on contrast-enhanced MR
      studies.
AB  - BACKGROUND AND PURPOSE: Our purpose was to determine the frequency of abnormal
      findings on contrast-enhanced high-resolution MR imaging studies in patients with
      sudden hearing loss. METHODS: Seventy-eight consecutive patients with sudden
      hearing loss underwent contrast-enhanced MR imaging of the temporal bone,
      cerebellopontine angle, and brain. Additional tests included audiologic
      examination, electrocochleography, fistula tests, and serologic tests for viral
      agents and autoimmune disorders. RESULTS: Probable causes of the sudden hearing
      loss in these patients included viral or immune-mediated disease, Meniere
      disease, vascular disorder, syphilis, neoplasm, multiple sclerosis, and
      perilymphatic fistula. Twenty-four (31%) of the 78 patients were found to have
      abnormal imaging results early in the course of their work up and treatment.
      CONCLUSION: The prevalence of abnormal findings on contrast-enhanced MR studies
      is higher than previously reported in patients with sudden hearing loss.

PMID- 9763373
TI  - Spontaneous labyrinthine hemorrhage in sickle cell disease.
AB  - We report the clinical and MR imaging findings in two African-American patients
      with manifestations of sickle cell disease affecting the inner ear. Both suffered
      sudden-onset sensorineural hearing loss and vestibular symptoms, and both had
      high labyrinthine signal on T1-weighted MR images attributed to labyrinthine
      hemorrhage. Follow-up studies of the first patient revealed a decrease in
      abnormal vestibular signal. Careful attention to the labyrinth on T1-weighted MR
      images can reveal vestibulocochlear clinical findings in sickle cell patients,
      with important implications for management and prognosis.

PMID- 9763374
TI  - Choroidal hemangioma: MR findings and differentiation from uveal melanoma.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to establish the MR imaging
      characteristics of choroidal hemangioma and to compare them with those of uveal
      melanoma. METHODS: Among 41 patients examined at 1.5 T (4-cm surface coil, T1
      weighted and fast spin-echo T2-weighted sequences), 25 had uveal melanoma and 16
      had circumscribed choroidal hemangioma. After i.v. bolus injection of
      gadopentetate dimeglumine, dynamic and T1-weighted sequences were acquired.
      RESULTS: In patients with choroidal hemangioma, uniform signal characteristics
      were detected on fast T2-weighted images. In 15 of 16 patients with choroidal
      hemangioma, lesions were isointense with vitreous on fast spin-echo T2-weighted
      images, whereas lesions in 24 of 25 patients with uveal melanoma were
      hypointense. Signal characteristics of uveal melanoma and hemangioma did not
      differ significantly on plain T1-weighted images. Enhancement was earlier and
      much stronger for circumscribed choroidal hemangioma than for uveal melanoma.
      After i.v. bolus application of gadopentetate dimeglumine, the increase of signal
      intensity was higher for circumscribed choroidal hemangioma (signal intensity
      ratio, 5.8) than for uveal melanoma (signal intensity ratio, 2.2). CONCLUSION:
      Circumscribed choroidal hemangioma may be difficult to differentiate from
      melanoma by ophthalmologic examination. Differentiation may not be possible if
      direct viewing of uveal space-occupying lesions is hampered by opaque vitreous
      media. The characteristic findings on fast spin-echo T2-weighted MR images and
      early enhanced images aid in differentiating choroidal hemangioma from uveal
      melanoma.

PMID- 9763375
TI  - Superior blowout fracture of the orbit: the blowup fracture.
AB  - We describe a patient who sustained a blowout fracture of the superior orbital
      roof without an orbital rim fracture. The initial CT study (obtained with 10-mm
      thick sections) did not show herniation of the intraorbital fat into the anterior
      cranial fossa; however, thin (3-mm-thick) direct orbital sections showed a
      fracture of the midportion of the superomedial orbital roof with displacement of
      the fracture fragment into the anterior cranial fossa.

PMID- 9763376
TI  - Traumatic subluxation of the globe into the maxillary sinus.
AB  - We report a case of complete traumatic subluxation of the globe into the
      maxillary sinus as documented by CT. The cornea sustained a mild epithelial
      abrasion but the globe was otherwise intact without signs of trauma.

PMID- 9763377
TI  - An unusual cause of otalgia.

PMID- 9763378
TI  - Neurotoxic potential of gadodiamide after injection into the lateral cerebral
      ventricle of rats.
AB  - PURPOSE: Results of a previous report showed that, if administered by
      intraventricular injection to access tissue normally protected by the blood-brain
      barrier, gadopentetate dimeglumine produced acute excitation, persistent ataxia,
      and widespread brain lesions in rats at 5-micromol/g brain but not at 3.8
      micromol/g brain. The present study using gadodiamide was undertaken to see
      whether the effects were agent-specific. METHODS: Rats, surgically prepared with
      a lateral ventricular cannula, were administered a slow injection at 2 microL/min
      of gadodiamide into the lateral ventricle, and behavioral and neuropathologic
      changes were noted. RESULTS: Both gadodiamide and gadopentetate dimeglumine
      produced focal and generalized myoclonus over several hours. Gadodiamide did not
      produce the medium-term tremor or persistent ataxia seen after treatment with
      gadopentetate dimeglumine. Neuropathologic changes developed over 1 to 3 days and
      took three distinct forms: vacuolated thalamic lesions closely resembling those
      produced by gadopentetate dimeglumine; small but similar vacuolated symmetrical
      caudate lesions not produced by gadopentetate dimeglumine; and severe swelling
      and astrocytic hypertrophy and hyperplasia in the cerebellar vermis, again not
      produced by gadopentetate dimeglumine. Unlike gadopentetate dimeglumine,
      gadodiamide produced no spinal cord lesions. The cerebellar changes were seen at
      1.25-micromol/g brain and above, behavioral changes at 2.5-micromol/g brain and
      above, and thalamic and caudate lesions at 10-micromol/g brain, the maximal dose
      used. Markedly reducing the rate of injecting the same volume over 28 hours
      prevented the acute excitation but did not reduce the severity of the morphologic
      effects. CONCLUSION: The acute excitatory effects of high intraventricular doses
      of gadopentetate dimeglumine and gadodiamide are similar and appear to be
      attributable to local action at the infusion site, but differences exist between
      the two agents in the character and topography of the distant morphologic
      changes. The cerebellum was the brain area most sensitive to gadodiamide in this
      experimental model. It is unlikely that gadodiamide would gain access to the
      brain at these tissue doses when used intravenously for conventional clinical
      imaging, but our experimental model suggested that it had some unexpectedly
      specific neuropathologic potential.

PMID- 9763379
TI  - Hemodynamic effects of middle cerebral artery stenosis and occlusion.
AB  - BACKGROUND AND PURPOSE: Middle cerebral artery (MCA) stenosis and occlusion may
      cause ischemic symptoms through both hemodynamic and embolic mechanisms. The
      purpose of this investigation was to determine the hemodynamic effects of these
      lesions. METHODS: Ten patients with angiographically confirmed symptomatic
      occlusion (n = 5) or stenosis (n = 5) of the M1 segment of the MCA were studied
      by clinical examination, arteriography, and positron emission tomography (PET).
      Arterial supply to the distal MCA territory was classified from a review of the
      angiogram as being through the stenosis or from pial collaterals from anterior or
      posterior cerebral arteries. Regional measurements of cerebral blood flow,
      cerebral blood volume, cerebral rate of oxygen metabolism, oxygen extraction
      fraction, and ratio of cerebral blood volume/cerebral blood flow (mean vascular
      transit time, MTT) were obtained using PET. Hemodynamic status was categorized
      from PET scans as stage 0, normal hemodynamics; stage 1, autoregulatory
      vasodilatation (increased MTT); or stage 2, increased oxygen extraction fraction.
      RESULTS: Of five patients with MCA occlusion, three had autoregulatory
      vasodilatation (stage 1) and two had increased oxygen extraction fraction distal
      to the lesion (stage 2). The MCA territory was supplied solely by pial
      collaterals in all five patients. Four of the five patients with focal MCA
      stenosis had normal hemodynamics (stage 0). One patient had stage 1 hemodynamic
      status. Blood flow to the MCA territory was through the stenosis in all patients;
      no pial collaterals were identified. CONCLUSION: The frequency of hemodynamic
      compromise in patients with MCA occlusion is high. Pial collateralization is not
      a specific sign of increased oxygen extraction fraction in patients with MCA
      occlusion.

PMID- 9763380
TI  - MR detection of hyperacute parenchymal hemorrhage of the brain.
AB  - BACKGROUND AND PURPOSE: The detection of hemorrhage in acutely ill patients is
      crucial to clinical management. The MR features that allow diagnosis of
      intracerebral hematomas of less than 24 hours' duration are described and the
      mechanistic basis of these features is investigated. METHODS: The clinical MR
      features of seven confirmed hyperacute intracerebral hematomas were compared with
      those of experimentally induced hematomas in a rat model in which detailed
      analyses of iron metabolism and morphometry were performed. RESULTS: In all
      patients and all animals, a hypointense rim on T2-weighted spin-echo images that
      was less marked on T1-weighted spin-echo images was seen surrounding a central
      isointense or heterogeneous region of hyperacute hematoma. Histologically, the
      clot showed interdigitation of intact erythrocytes and tissue at the hematoma
      tissue interface without significant hemosiderin, ferritin, or phagocytic
      activity. Biochemically, the iron from the extravasated blood was present only as
      heme proteins within the first 24 hours. CONCLUSION: The hypointense rim on T2
      weighted images, and to a lesser extent on T1-weighted images, is a distinctive
      feature of hyperacute hematoma. This pattern is consistent with magnetic
      susceptibility variations of paramagnetic deoxygenated hemoglobin within intact
      erythrocytes at a microscopically irregular tissue-clot interface. The detection
      of hemorrhage is important in the management of patients with acute stroke.

PMID- 9763381
TI  - Small rosarylike infarctions in the centrum ovale suggest hemodynamic failure.
AB  - BACKGROUND AND PURPOSE: Lesions in the centrum ovale may be classified as
      microangiopathic (lacunar) lesions and hemodynamic infarctions. To distinguish
      between them, a size of more than 2 cm has been postulated for hemodynamic
      infarctions. The reliability of this criterion was assessed with MR imaging.
      METHODS: In 16 patients with unilateral or bilateral occlusion or high-grade
      stenosis of the internal carotid artery (ICA), CO2 testing revealed an
      ipsilateral hemodynamic failure. Each hemisphere in these patients was assessed
      separately for the presence and size of centrum ovale lesions. RESULTS: Five of
      the 16 patients suffered from large cortical infarctions with a probable embolic
      pathogenesis. In the remaining 11 patients (22 hemispheres), a hemodynamic
      failure was found in 15 hemispheres, due to occlusion (13 hemispheres) or high
      grade ICA stenosis (two hemispheres). MR imaging revealed centrum ovale
      infarctions with a size of more than 2 cm in three of the 15 hemispheres. In
      eight hemispheres, multiple small lesions (< 1.5 cm; three to 30 per hemisphere)
      could be found with a rosarylike or sickle-shaped distribution. In none of these
      eight cases did MR images show lacunar infarctions in the typical regions of the
      brain. CONCLUSION: Our results favor the assumption that the MR finding of
      multiple small (< 1.5 cm) rosarylike lesions in the centrum ovale seems to be
      typical in patients with hemodynamic failure due to severe ICA disease.

PMID- 9763382
TI  - Acute postictal cerebral imaging.
AB  - BACKGROUND AND PURPOSE: Imaging of postictal patients is performed to investigate
      causes of seizure, such as space-occupying lesions or other "structural"
      processes; however, abnormalities may be found that reflect physiological or
      pathologic alterations due to seizure activity. The purpose of this study was to
      determine the brain imaging findings in patients in the immediate postictal
      period who presented with altered mental status or weakness. METHODS: Ten
      patients who were examined for postictal neurologic derangement were studied
      (nine by CT and one by MR imaging) within 12 hours of ictus. Four of the CT
      studies and the one MR study included administration of contrast material. Follow
      up examinations were performed 1 day to 11 months later. These studies were
      reviewed retrospectively. RESULTS: CT findings included focal gyral swelling
      (10/10), effacement of adjacent cortical sulci (2/10), decreased gyral
      attenuation by CT (8/9), and mild to moderate gyral enhancement after injection
      of contrast material (5/5). MR imaging findings included gyral swelling,
      increased signal intensity on T2-weighted images, and enhancement after injection
      of contrast agent. The abnormalities were located in the frontal lobes (9/10,
      with bilateral involvement in 6/10), the parietal lobes (4/10), the temporal
      lobes (2/10), and the occipital lobe (1/10). Follow-up studies revealed complete
      or subtotal reversal of these abnormalities. CONCLUSION: Although there are
      numerous causes of gyral swelling and enhancement, such as infarction and
      neoplasm, if these conditions are reversible and correspond to clinical findings,
      then the differential diagnosis is narrowed to postictal change, reversible
      ischemia, complicated migraine, or resolved inflammation/infection.

PMID- 9763383
TI  - MR identification of white matter abnormalities in multiple sclerosis: a
      comparison between 1.5 T and 4 T.
AB  - BACKGROUND AND PURPOSE: Although MR spectroscopy and functional MR imaging of the
      brain have been successful at 4 T, conventional fast spin-echo imaging of the
      brain at 4 T has not been adequately evaluated. The purpose of this study was to
      compare the detection of white matter abnormalities in multiple sclerosis (MS) at
      1.5 T and 4 T. METHODS: Fifteen patients with clinically definite MS were imaged
      at both 1.5 T and 4 T within a 1-week period. Comparison was made between fast
      spin-echo long-TR images at both field strengths. Pulse sequences were tailored
      to maximize resolution and signal-to-noise ratio in clinically relevant imaging
      times (< 7 min). Four interpreters independently reviewed the images obtained at
      both field strengths in separate sessions and evaluated them for lesion
      identification, size, characterization, and subjective resolution. Differences in
      interpretations at 1.5 T and 4 T were subsequently recorded. RESULTS: Images
      obtained at 4 T showed a mean of 88 more lesions as compared with images obtained
      at 1.5 T. All the lesions measured less than 5 mm and were typically aligned
      along perivascular spaces. Twenty-five consensually identified lesions on 4-T
      images were not seen at all on 1.5-T images. Moreover, 4-T images showed 56
      additional consensually identified lesions, which were indistinct and seen only
      in retrospect on 1.5-T images. These lesions were frequently (n = 48) identified
      in large confluent areas of white matter signal intensity abnormality at 1.5 T.
      All observers also agreed that 4-T images subjectively enhanced the perception of
      normal perivascular spaces and small perivascular lesions. CONCLUSION: MR imaging
      at 4 T can depict white matter abnormalities in MS patients not detectable at 1.5
      T through higher resolution with comparable signal-to-noise ratio and imaging
      times.

PMID- 9763384
TI  - MR findings in growth hormone deficiency: correlation with severity of
      hypopituitarism.
AB  - BACKGROUND AND PURPOSE: Growth hormone deficiency may present as an isolated
      deficit (IGHD) or in association with multiple deficiencies (MPHD). Previous
      studies have not compared the MR imaging findings with the severity of
      hypopituitarism. Our purpose was to determine whether MR imaging can distinguish
      between IGHD and MPHD. METHODS: Forty-four patients with growth hormone
      deficiency who were examined by MR imaging were included in this retrospective
      study. On the basis of the endocrinologic findings, 21 were determined to have
      IGHD and 23 to have MPHD. The presence, size, location, and morphologic
      characteristics of the stalk, the neurohypophysis, and the adenohypophysis were
      recorded in each case. Findings in the two groups were compared. Statistical
      significance was determined by t-test. RESULTS: The stalk was normal in one
      patient with IGHD and in none of those with MPHD; it was truncated or thin in 19
      patients with IGHD (90%) and in only one with MPHD (4%); it was absent in 22
      patients with MPHD (96%) and in only one patient with IGHD (5%). These
      differences between the two groups were highly significant. In 81% of the IGHD
      patients and in 91% of the MPHD patients the location of the neurohypophysis was
      ectopic. This difference between the two groups was not significant. Among IGHD
      patients, the adenohypophysis was of normal size in 13 patients (62%), small in
      six (29%), and absent in two (9%); the corresponding findings in MPHD patients
      were seven (30%), six (26%), and 10 (44%). CONCLUSION: The majority of IGHD
      patients had a truncated or thin stalk and a normal or small adenohypophysis. An
      absent stalk and adenohypophysis are characteristic of MPHD. MR imaging can
      contribute to the prediction of the pattern and severity of hypopituitarism in
      patients with growth hormone deficiency.

PMID- 9763385
TI  - Differential aging of the human striatum: a prospective MR imaging study.
AB  - BACKGROUND AND PURPOSE: Advancing age is associated with declines in motor
      function; understanding age-related changes in the basal ganglia, therefore, is
      imperative for comprehension of such functional changes. The purpose of this
      study was to examine the age, sex, and hemispheric differences in volume of the
      caudate nucleus, the putamen, and the globus pallidus. METHODS: In a sample of
      148 healthy right-handed adults (18-77 years old) with no evidence of age-related
      motor disorders, we estimated the volume of the head of the caudate nucleus, the
      putamen, and the globus pallidus from MR images. RESULTS: The analyses revealed
      bilateral age-related shrinkage of the head of the caudate nucleus and the
      putamen in both sexes. In men, the age-related shrinkage of the caudate was
      stronger on the left, whereas, in women, the opposite trend was evident. In both
      sexes, age-related shrinkage of the right putamen was greater than of its left
      counterpart. The mild bilateral age-related shrinkage of the globus pallidus was
      observed only in men. In both sexes, we observed significant rightward asymmetry
      in the putamen, significant leftward asymmetry in the caudate, and no asymmetry
      in the globus pallidus. CONCLUSIONS: Bilateral age-related shrinkage of the
      neostriatum is found in healthy adults. The shrinkage of the globus pallidus is
      less pronounced and may be restricted to men only.

PMID- 9763386
TI  - Abnormal cerebral activation associated with a motor task in Tourette syndrome.
AB  - BACKGROUND AND PURPOSE: In Gilles de la Tourette syndrome, PET scanning and EEG
      suggest an abnormal organization of the sensorimotor cortex and basal ganglia.
      The purpose of this study was to use functional MR imaging to study activation in
      the sensorimotor cortex in patients with Tourette syndrome. METHODS: From echo
      planar images acquired during intermittent performance of a finger-tapping task,
      the location of activated pixels was determined by means of conventional signal
      processing methods. In five patients with Tourette syndrome and five healthy
      volunteers, the number of activated pixels in the sensorimotor cortices and
      supplementary motor areas were counted. The area over which the activation was
      distributed was calculated. RESULTS: In the five patients, the average number of
      pixels activated during the finger-tapping task in the sensorimoter cortices and
      supplementary motor area (69.4 pixels) exceeded that in the volunteers (49.2
      pixels). The difference was significant. The area over which the pixels was
      distributed was significantly larger (25.4 vs 13.8 cm2). CONCLUSION: Motor
      function is organized differently in patients with Tourette syndrome than in
      healthy subjects.

PMID- 9763387
TI  - Integral and shell-MIP display algorithms in MR and CT three-dimensional models
      of the brain surface.
AB  - BACKGROUND AND PURPOSE: Our purpose was to demonstrate the use of integral and
      shell maximum intensity projection (shell-MIP) display algorithms in the 3-D CT
      and MR depiction of cerebral gyral and surface venous anatomy and disorders.
      These new algorithms are compared against MIP and shaded-surface-display (SSD)
      algorithms. METHODS: Integral and shell-MIP displays were generated from a
      specified number of proximal surface voxel layers in a 3-D model. Algorithmic
      models were compared on nine contrast-enhanced spoiled gradient-recalled
      acquisition in a steady state (SPGR) MR venograms for brain surface anatomic
      identification and detail. Seven CT venograms were compared for conspicuity of
      filling defects. Twelve contrast-enhanced preoperative planning 3-D MR models
      were rated for neurosurgical utility. RESULTS: A shell-MIP score of 7.00 and an
      integral score of 6.78 represented the highest mean subjective MR gyral quality
      (1-10 scale) followed by an SSD score of 3.89 and an MIP score of 1.06. Mean
      confidence scores for MR central sulcus identification (1-10 scale) were shell
      MIP, 7.67; integral, 7.00; SSD, 3.22; and MIP, 1.00. Mean superficial venous
      quality MR ratings (1-10 scale) were shell-MIP, 8.22; MIP, 7.39; integral, 7.00;
      and SSD, 3.72. The mean number of cortical veins draining into each side of the
      superior sagittal sinus on MR was as follows: MIP, 6.19; integral, 6.06; shell
      MIP, 5.94; and SSD, 3.81. Mean confidence scores for filling defect
      identification on CT venograms (1-5 scale) revealed a shell-MIP score of 4.36 and
      an integral score of 4.29 to be superior to a MIP score of 3.00. In selected
      cases, 3-D presurgical planning, prior to tumor resection, was clinically useful.
      CONCLUSION: Integral and shell-MIP are useful 3-D display algorithms for
      simultaneous display of superficial cerebral veins and gyri on MR images and of
      thrombosis on CT venograms.

PMID- 9763388
TI  - Iatrogenically induced cortical blindness associated with leptomeningeal
      enhancement.
AB  - Leptomeningeal enhancement is usually infective or neoplastic in origin. We
      present a case in which a patient received total parenteral nutrition via a
      catheter unknowingly placed within the right vertebral artery. We postulate that
      the hyperosmolar nature of the infused solution induced temporary osmotic
      disruption of the blood-brain barrier, resulting in cortical blindness associated
      with localized leptomeningeal enhancement.

PMID- 9763389
TI  - Follow-up study after intracranial percutaneous transluminal cerebral balloon
      angioplasty.
AB  - BACKGROUND AND PURPOSE: Our objective was to find the specific angiographic
      characteristics of atherosclerotic lesions that indicate suitability for
      intracranial percutaneous transluminal cerebral balloon angioplasty (PTCBA).
      METHODS: Forty-two clinically symptomatic patients with 42 hemodynamically
      significant intracranial lesions (>70% stenosis) were treated by PTCBA between
      January 1992 and May 1996. Before treatment, the patients were assigned to three
      groups according to the angiographic characteristics of the lesions, as follows:
      type A, short (5 mm or less in length) concentric or moderately eccentric lesions
      less than totally occlusive; type B, tubular (5 to 10 mm in length), extremely
      eccentric or totally occluded lesions, less than 3 months old; and type C,
      diffuse (more than 10 mm in length), extremely angulated (>90 degrees) lesions
      with excessive tortuosity of the proximal segment, or totally occluded lesions,
      and 3 months old or older. The patients were followed up for a period of 1 month
      to 6 years to compare the results of PTCBA treatment among the three groups.
      Primary end points were death, stroke, or bypass surgery. RESULTS: The clinical
      success rates for the type A, B, and C groups were 92%, 86%, and 33%,
      respectively. Cumulative risks of fatal or nonfatal ischemic stroke or
      ipsilateral bypass surgery in type A, B, and C groups were 8%, 26%, and 87%,
      respectively. The cumulative risk of 8% among patients in the type A group
      appeared to be smaller than in studies reported in the literature. CONCLUSION:
      PTCBA for intracranial simple (type A) lesions yields a favorable clinical
      outcome for symptomatic patients.

PMID- 9763390
TI  - Carotid artery balloon angioplasty and stenting (CABAS): a neuroradiologic
      perspective.

PMID- 9763391
TI  - Thromboembolic events associated with the treatment of cerebral aneurysms with
      Guglielmi detachable coils.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to document the prevalence,
      radiologic appearance, and treatment of thromboembolic events related to GDC
      embolization of cerebral aneurysms. METHODS: The clinical and radiologic records
      of all patients undergoing GDC treatment of intracranial aneurysms at our
      institution were reviewed. All cases in which unexpected complications occurred
      were selected. Those complications related to presumed thromboembolic events were
      analyzed. RESULTS: Of 59 patients (60 aneurysms) treated with GDCs, 17 (28%)
      experienced thromboembolic events. Seven patients had transient ischemic attacks
      and 10 had strokes. In 10 patients, the deficits occurred during or immediately
      after the procedure; in the rest, the complications were delayed. In six
      patients, all radiologic investigations were negative for infarction and in seven
      patients, CT scans showed new ischemic lesions. In four patients, MR imaging
      alone showed infarcts, and in four of nine patients who underwent subsequent
      angiography, acute ischemic findings were demonstrated. Eight patients were
      treated with volume expansion, eight with full heparinization, and one patient
      underwent intraarterial thrombolysis. Clinical outcome was excellent or good in
      14 of 17 patients, with only three patients (5%) incurring permanent neurologic
      deficits. CONCLUSION: Thromboembolic events related to GDC treatment may be more
      common than has been reported in the literature. In our experience, this rate was
      28%, with persisting deficits in 5%. These events can occur after uncomplicated
      procedures and may be unaccompanied by radiologic findings. Clinical outcome is
      usually favorable.

PMID- 9763393
TI  - Endovascular treatment of basilar tip aneurysms after direct puncture of the
      vertebral artery.
AB  - Basilar aneurysms that are not amenable to standard endovascular treatment via
      the femoral approach because catheterization is difficult pose a rare but serious
      problem. We present two cases of basilar tip aneurysms successfully treated by
      the endovascular route after direct puncture of the right vertebral artery. In
      both patients, the left vertebral artery was tortuous, small, and irregular, and
      the ostium of the right vertebral artery was not accessible by the femoral
      approach.

PMID- 9763392
TI  - Transcranial Doppler sonographic monitoring during cerebral aneurysm
      embolization: a preliminary report.
AB  - BACKGROUND AND PURPOSE: The wide application of embolization in the treatment of
      aneurysms has created the need for an intraprocedural means to anticipate a poor
      outcome by monitoring hemodynamic changes in the brain. METHODS: Transcranial
      Doppler sonography was used to monitor flow velocity in the middle cerebral
      artery (MCA) in 23 patients undergoing embolization with Guglielmi detachable
      coils (GDCs) of either incidental or symptomatic intracranial aneurysms.
      Sonographic values were recorded from the ipsilateral MCA at the beginning,
      middle, and end of the interventional procedure and 24 hours afterward. RESULTS:
      No complications occurred in 15 patients. In these cases, sonography showed an
      average decrease in MCA flow velocity of 2.7% after GDC application, returning to
      baseline at the end of treatment and then increasing by about 17% 24 hours later.
      In four patients with vasospasm on posttreatment angiograms, MCA flow velocity
      increased to values higher than 120 cm/s after GDC application, returning to
      baseline after 24 hours. In four patients with ischemic complications (two
      transient ischemic attacks, one stroke, one vascular death), MCA flow velocity
      decreased more than 30% and did not return to preoperative values within 24
      hours. CONCLUSION: The application of transcranial Doppler sonographic monitoring
      during endovascular treatment may help to identify patients at risk for
      posttreatment cerebral ischemia.

PMID- 9763394
TI  - Collateral circulation and outcome after basilar artery thrombolysis.
AB  - BACKGROUND AND PURPOSE: This study was undertaken to examine the relationship
      between collateral flow and outcome after local intraarterial thrombolytic
      treatment for basilar artery thrombosis. METHODS: Twenty-four patients with
      symptomatic basilar thrombosis were treated with intraarterial urokinase.
      Angiograms at the time of treatment were analyzed to characterize collateral
      flow. The number of posterior communicating arteries (PCoAs) and the degree of
      collateral filling of the basilar artery were then compared with symptom duration
      before treatment, with Glasgow Coma Scale (GCS) score at the time of treatment,
      with 90-day modified Rankin score, and with 90-day survival status. RESULTS: Of
      the 20 patients who had carotid artery injections at the time of the thrombolytic
      procedure, two had no PCoA, eight had one PCoA, and 10 had two PCoAs. Nine had no
      collateral opacification of the basilar artery, six had collateral opacification
      of the distal basilar artery, and five had collateral opacification of the distal
      and proximal basilar artery. Ninety-day survival was 38%; 25% of patients had
      good neurologic outcomes. No correlation was found between the number of PCoAs
      and symptom duration, pretreatment GCS score, survival, or neurologic outcome.
      Duration of symptoms before treatment was longer in patients with collateral flow
      to the basilar artery. Basilar artery collateral flow did not correlate with
      survival, but it did correlate with neurologic outcome for the 12 patients with
      middle or distal basilar artery thrombus in whom collateral flow to the basilar
      artery was assessed (83% with collateral flow had good neurologic outcomes, but
      only 17% without collateral flow had good outcomes). All six patients with
      proximal basilar artery thrombus in whom collateral flow was assessed died,
      independent of the collateral flow observed. CONCLUSION: In symptomatic acute
      basilar artery thrombosis, neurologic outcome was better after intraarterial
      thrombolysis in patients who had collateral filling of the basilar artery, except
      in cases of proximal basilar thrombosis. Patients with collateral filling of the
      basilar artery also tolerated longer symptom duration.

PMID- 9763395
TI  - The use of electrolytically detachable coils in treating high-flow arteriovenous
      fistulas.
AB  - BACKGROUND AND PURPOSE: High-flow arteriovenous fistulas (AVFs) are commonly
      treated by using an endovascular approach with a variety of materials. The use of
      a Guglielmi electrolytically detachable coil (GDC) provides the ability to
      reposition or remove the coil if its position is not optimal and may minimize the
      risk of coil migration or distal embolization. This study reports our experience
      in using these coils alone or in combination with other materials in the
      treatment of intracranial and cervical high-flow fistulas. METHODS: Twelve
      patients with AVFs were treated with GDCs via the transvenous or transarterial
      transfistulous routes. The six dural AVFs treated transvenously were also treated
      transarterially, and the GDCs were combined with fibered coils in three of these
      patients and in two other patients with pial AVFs. All patients have been
      clinically followed up for 12 to 48 months (mean, 28 months). RESULTS:
      Angiographic obliteration was obtained in all 12 patients. The fistulas have
      remained closed in 11 patients, as ascertained by angiographic confirmation in
      two patients and by clinical examination in nine patients. The one patient with
      recurrence experienced neurologic improvement and refused further treatment. GDCs
      required repositioning before detachment in seven patients, and no migration
      occurred after detachment. CONCLUSION: GDCs are useful for the treatment of high
      flow AVFs. They afford more control in the placement of coils and may provide an
      anchoring point for more thrombogenic materials.

PMID- 9763396
TI  - Performance characteristics of microcatheter systems in a standardized tortuous
      pathway.
AB  - BACKGROUND AND PURPOSE: Published reports of controlled experiments designed to
      evaluate the performance of over-the-wire microcatheter systems are rare and have
      often been based on subjective impressions from small clinical series. This
      investigation was designed to compare the load forces required to propel state-of
      the-art, hydrophilically coated microcatheters from each of four manufacturers
      through a standardized tortuous pathway constructed of polytetrafluoroethylene
      tubing. METHODS: Currently available hydrophilically coated microcatheters were
      provided by four manufacturers. A 20-cm long, three-dimensional pathway
      simulating the intracranial carotid circulation was constructed of 0.065-in.
      (inner diameter) polytetrafluoroethylene tubing and immersed in a water bath at
      37 degrees C. Testing was performed using an Instron tabletop load frame fitted
      with a 2-lb load cell. Durability and load force tests were conducted using a
      0.014-in. stainless steel noncoated guidewire, with the wire tip protruding 1 cm
      beyond the catheter tip. At least four samples of microcatheters from each
      manufacturer were tested. RESULTS: Extensive trackability testing of the
      guidewire alone established reproducible performance with maximum load forces of
      less than 8 g. Maximum gram forces for the four reinforced microcatheters were
      not greatly different, measuring between 9 and 14 g. Excessive buckling of the
      only nonreinforced catheter was initially overcome early in the pathway in a
      staccato, stepwise fashion. After reaching a critical load, however, the catheter
      and guidewire prolapsed. CONCLUSION: All reinforced microcatheters tested
      established good and reproducible performance in our model. Reinforced
      microcatheters provided superior trackability over the one nonreinforced device
      tested.

PMID- 9763397
TI  - Presumed venous infarction in spinal decompression sickness.
AB  - We describe the serial MR imaging findings in a patient with spinal decompression
      sickness. In the acute phase, the spinal cord was swollen, with increased T2
      signal in the posterior part of the column; 1 month later, marked contrast
      enhancement was noted in the same location; and 2 months later, the swelling and
      T2 signal had decreased. MR imaging may facilitate the early diagnosis of spinal
      decompression sickness.

PMID- 9763398
TI  - Comparison of in vivo and in vitro deposition of rhodamine and fluorescein in
      hair.
AB  - A direct differentiation of the internal and external drug-deposition pattern
      into hair was made using two fluorescent dyes and fluorescence microscopy after
      systemic administration to mice or external exposure of untreated hair. Mice (23
      days old, C57 and Balb/C) were administered either rhodamine or fluorescein
      intraperitoneally at varied doses on 3 consecutive days of 3 weeks, and hair was
      sampled 1 week later. Another group was given 10 mg/kg rhodamine or 100 mg/kg
      fluorescein and sampled at time points from 5 min to 168 hr. The time courses of
      external deposition of rhodamine and fluorescein into untreated hair were
      examined after hair was soaked in 0.1 mg/ml solutions at pH 3, pH 6, and pH 9
      aqueous buffer or methanol. The hair was then extracted in pH 6 phosphate buffer
      or methanol for 24 hr. In vivo accumulation was distinguishable as fluorescent
      bands along the length of the hair for rhodamine and fluorescein. The pattern of
      in vivo deposition appears to arise from the rapid accumulation within the cortex
      and medulla, with little deposition evident in the cuticle. Neither phosphate
      buffer nor methanol washes affected the intensity of fluorescence in the hair.
      External loading of rhodamine into the hair resulted in staining of the junctions
      of cuticle scales. This pattern persisted even after 12 hr of solution exposure.
      Extraction with pH 6 phosphate buffer or methanol did not remove rhodamine.
      Fluoroscein followed a similar pattern, with maximum fluorescence when hair was
      loaded in pH 6 100mM phosphate buffer and nominal staining when loaded in pH 9
      100 mM Tris buffer or methanol. Soaking the hair in pH 6 buffer, but not
      methanol, removed some fluorescein. These results demonstrate that compounds in
      the circulation can rapidly diffuse into the forming cortex and medulla, where
      rapid associations occur with elongating intermediate filaments specific to the
      medulla and cortex. These compounds can become significantly occluded within the
      mature matrix and are resistant to removal in aqueous or methanolic solutions.

PMID- 9763399
TI  - Disposition of L-732,531, a potent immunosuppressant, in rats and baboons.
AB  - L-732,531 is a semi-synthetic analog of the macrolide tacrolimus (Prograf(R)).
      Like tacrolimus, L-732,531 is a potent immunosuppressant. In this study, its
      absorption, distribution, metabolism, and excretion were studied in rats and
      baboons. In rats, its blood and plasma levels were similar, whereas in baboons,
      its blood levels were, on average, twice as high as those in plasma. This was
      consistent with the in vitro blood-to-plasma ratio of L-732, 531, which in these
      two species, as well as in humans, was much lower than that of tacrolimus and
      showed a minimal concentration dependence. After iv administration to rats, the
      blood and plasma clearance of L-732,531 decreased from approximately 60 ml/min/kg
      at 0.2 mg/kg to 30 ml/min/kg when dosed at 1 and 3 mg/kg. After oral
      administration, plasma area under the concentration vs. time curve (AUC) and
      maximal plasma concentration (Cmax) increased more than proportionally to the
      dose. At 1, 5, and 15 mg/kg, plasma AUC was 29, 466, and 2832 ng.hr/ml,
      respectively, and Cmax was 10, 129, and 304 ng/ml, respectively. Bioavailability,
      although compromised by nonlinear kinetics, was estimated to be between 8% and
      18%. In baboons, the clearance of L-732,531 was lower than that in rats,
      especially when calculated from blood concentrations (12 ml/min/kg at 0.2 mg/kg
      and 8 ml/min/kg at 1 mg/kg). After oral dosing, baboon plasma AUC and Cmax were
      much lower than those in rats, but as in rats, they increased more than
      proportionally with increasing doses. The bioavailability of L-732,531 in baboons
      was estimated at 3%, 9%, and 24% when animals were dosed at 5, 15, and 26 mg/kg
      po, respectively. After oral administration of [3H]L-732,531 at 5 mg/kg,
      approximately 32% of the radioactivity was recovered in bile and urine of rats,
      compared with 9% in baboons. High-performance liquid chromatography profiles of
      rat and baboon plasma, bile, urine, and feces indicated that L-732,531 was
      metabolized extensively to a complex mixture of products. Some intact parent drug
      was observed in feces of orally dosed animals, indicating incomplete absorption.
      In vitro, L-732,531 was metabolized more extensively by baboon liver microsomes
      than rat or human microsomes. Its metabolism in human liver microsomes was shown
      to be catalyzed primarily by cytochrome P450 3A isozymes.

PMID- 9763401
TI  - Identification of the human liver cytochrome P450 enzymes involved in the in
      vitro metabolism of a novel 5-lipoxygenase inhibitor.
AB  - In vitro studies were conducted to identify the hepatic cytochrome P450 (CYP)
      forms involved in the oxidative metabolism of [14C]ABT-761 and its N
      dehydroxylated metabolite, [14C]ABT-438, by human liver microsomes. The two
      compounds were metabolized by parallel pathways, to form the corresponding
      methylene bridge hydroxy metabolites. There was no evidence of sulfoxidation
      and/or ring hydroxylation. Over the ABT-761 and ABT-438 concentration ranges
      studied (1-300 microM), the rate of NADPH-dependent hydroxylation was linear with
      respect to substrate concentration ([S]) and did not conform to saturable
      Michaelis-Menten kinetics. Under these conditions ([S] < KM), the intrinsic
      clearance (Vmax/KM) of ABT-438 was 10-fold higher than that of ABT-761 (1.7 +/-
      0.8 vs. 0.17 +/- 0.06 microl/min/mg, mean +/- SD, N = 3 livers). The
      hydroxylation of both compounds was shown to be highly correlated (r = 0.83, p <
      0.01, N = 11 different human livers) with CYP3A-selective erythromycin N
      demethylase activity, and the correlation between ABT-761 hydroxylation and
      tolbutamide hydroxylase (CYP2C9-selective) activity (r = 0.63, p < 0.05, N = 10)
      was also statistically significant. Ketoconazole (2.0 microM), a CYP3A-selective
      inhibitor, inhibited the hydroxylation of both compounds by 53-67%, and
      sulfaphenazole (CYP2C9-selective) decreased activity by 10-20%. By comparison,
      alpha-naphthoflavone, a known activator of CYP3A, stimulated the hydroxylation of
      ABT-761 (8-fold) and ABT-438 (4-fold). In addition, the abundance-normalized
      rates of cDNA-expressed CYP-dependent metabolism indicated that hydroxylation was
      largely mediated (66-86%) by CYP3A(4). Therefore, it is concluded that the
      hydroxylation of ABT-761 and ABT-438 (</=10 microM) is primarily mediated by
      CYP3A, although CYP2C9 may play an ancillary role.

PMID- 9763400
TI  - Metabolism of carvedilol in dogs, rats, and mice.
AB  - The excretion and biotransformation of carvedilol [1-[carbazolyl-(4)-oxy]-3-[(2
      methoxyphenoxyethyl)amino]-2-p ropanol], a new, multiple-action, neurohormonal
      antagonist that exhibits the combined pharmacological activities of beta
      adrenoreceptor antagonism, vasodilation, and antioxidation, were investigated in
      dogs, rats, and mice. Carvedilol was absorbed well, and biliary secretion was
      predominant in each species. Carvedilol was metabolized extensively in each
      species, and elimination of unchanged compound was minor in bile duct
      catheterized rats and dogs. In dogs, glucuronidation of the parent compound and
      hydroxylation of the carbazolyl ring, with subsequent glucuronidation, were the
      major metabolic pathways. Rats showed the simplest metabolite profile; the
      primary metabolites were formed by hydroxylation of the carbazolyl ring, with
      subsequent glucuronidation. Mice displayed the most complicated metabolite
      profile; glucuronidation of the parent compound and hydroxylation of either the
      carbazolyl or phenyl ring, with subsequent glucuronidation, were the major
      metabolic routes. O-Dealkylation was a minor pathway in all species examined.

PMID- 9763402
TI  - Biodistribution and clearance of 125I-labeled C-reactive protein and 125I-labeled
      modified C-reactive protein in CD-1 mice.
AB  - Iodinated forms of C-reactive protein (CRP), soluble modified CRP (mCRP-sol), and
      suspended mCRP (mCRP-susp) were injected iv into CD-1 mice, for analysis of their
      pharmacokinetics (PK) and biodistribution (BD). The plasma half-life of 125I-CRP,
      measured as 4.7 hr, agrees closely with previous reports. The PK and BD
      characteristics for 125I-mCRP-sol and 125I-mCRP-susp were comparable to each
      other and were distinctly different from those measured for CRP. Whereas
      approximately 50% of 125I-CRP was recoverable from plasma 5 min after injection,
      only approximately 5% of 125I-mCRP was similarly recoverable. The estimated
      volume of distribution at steady state calculated for either form of 125I-mCRP
      was approximately 10-fold greater than that calculated for 125I-CRP (23. 4-27.6
      and 2.4 ml, respectively). The estimated mean residence times for 125I-mCRP were
      approximately 2 times longer than that measured for 125I-CRP (9.5-11.5 hr,
      compared with 4.9 hr). At both 4- and 24-hr time points, substantial amounts of
      125I-mCRP were selectively distributed in the bone marrow. At 24 hr,
      approximately 25% of the injected 125I-mCRP-sol and 125I-mCRP-susp was localized
      to the bone marrow (corresponding to 92% of injected dose/g of tissue). At this
      time point, only 8% (or 27%/g) of 125I-CRP was localized to the bone marrow.
      Overall, the data presented indicate that 1) mCRP has PK and BD characteristics
      distinct from those of CRP; 2) injected mCRP, although it is rapidly cleared from
      the general circulation, accesses large body areas and is selectively localized
      to the bone marrow; and 3) all forms of CRP appear to be excreted in the urine.

PMID- 9763403
TI  - Disposition of the antipsychotic agent CI-1007 in rats, monkeys, dogs, and human
      cytochrome P450 2D6 extensive metabolizers. Species comparison and allometric
      scaling.
AB  - The disposition of CI-1007 (I), an antipsychotic dopamine agonist, was studied
      after iv or po administration to rats, monkeys, and dogs and po administration to
      human cytochrome P450 2D6 extensive metabolizers (EMs). I was extensively
      metabolized after po administration, with high hepatic clearance (CL) values and
      negligible urinary excretion. Values for systemic plasma CL (28-40 ml/min/kg)
      suggested hepatic plasma flow-limited CL. The oral CL of I was similar among the
      species. Strong correlation was achieved in interspecies scaling for CL. After
      oral administration of [14C]I, the major route of 14C elimination in rats was in
      the bile (64%), followed by feces (29%) and urine (3.2%). Fecal excretion (64%)
      was the major route of 14C elimination in monkeys, followed by urine (14%). Three
      hydroxy metabolites, i.e. PD 147693 (II), PD 149394 (III), and PD 155144 (IV),
      and two sulfates, i.e. PD 163637 (VI) and PD 163639 (VIII), were identified in
      monkey plasma, urine, or feces. VIII was the major metabolite excreted in monkey
      urine, and VI was the major component in feces. Trace amounts of II, VI, and VIII
      were detected in the plasma and urine of human EMs but not in rats or dogs. II is
      an active metabolite that was present in all species. After oral administration,
      observed maximal plasma concentration and AUC values for II were higher than the
      corresponding values for I in dog plasma, approximately 20-40% of the values for
      I in monkeys and human EMs, and <5% of the values for I in rat plasma. Although
      the metabolic profiles differ among species, strong correlation was achieved in
      allometric scaling because the elimination of I from the body is mainly limited
      by hepatic blood flow.

PMID- 9763404
TI  - Comparative inhibition of human cytochromes P450 1A1 and 1A2 by flavonoids.
AB  - Flavonoids are a class of dietary phytochemicals that modulate various biological
      activities. The effects of flavone and five hydroxylated derivatives on the
      methoxyresorufin O-demethylase activity catalyzed by cDNA-expressed human
      cytochromes P450 (CYP)1A1 and 1A2 were examined. Flavone was a less potent
      inhibitor of CYP1A1 (IC50 = 0.14 microM) than CYP1A2 (IC50 = 0.066 microM). Four
      hydroxylated flavone derivatives (3-hydroxy-, 5-hydroxy-, 7-hydroxy-, and 3,7
      dihydroxyflavone) were also potent inhibitors of CYP1A1 (IC50 < 0.1 microM) and
      CYP1A2 (IC50 < 0.3 microM). For CYP1A1, 7-hydroxyflavone exhibited a competitive
      mode of inhibition, with a Ki value of 0.015 microM and 6-fold selectivity for
      CYP1A1 over CYP1A2. 3,5,7-Trihydroxyflavone (galangin) showed the highest potency
      toward CYP1A2. The inhibition by galangin of the methoxyresorufin O-demethylase
      activity of CYP1A2 was mixed-type, with a Ki value of 0.008 microM. Galangin
      showed 5-fold selectivity in its inhibition of CYP1A2 over CYP1A1. The results
      indicate that some flavonoids have high potencies and selectivities for
      inhibition of CYP1A isozymes. This may have important implications for cancer
      prevention, as well as other pharmacological and toxicological effects of these
      compounds.

PMID- 9763405
TI  - Metabolism of alpha-phosphonosulfonate squalene synthase inhibitors. I.
      Disposition of a farnesylethyl alpha-phosphonosulfonate and ester prodrugs in
      rats.
AB  - The disposition of I [(E,E)-6,10,14-trimethyl-1-phosphono-5,9, 13-pentadecatriene
      1-sulfonic acid] and its mono- (II), di- (III), and triester (IV) prodrugs in
      rats was studied with 14C-labeled compounds. After iv administration of I (15
      micromol/kg), radioactivity in plasma was measurable up to 96 hr and averaged 0.
      026 microg-eq/ml. I accounted for >50% of the radioactivity in plasma and had an
      apparent half-life of 4 hr. After oral administration of the same dose, the
      maximal plasma concentration of radioactivity averaged 0.108 microg-eq/ml at 6
      hr. In 96 hr, 19 and 73% of the iv dose and 2 and 97% of the po dose was excreted
      in urine and feces, respectively. The absorption was 2.4%, based on the plasma
      data. In 12 hr after an iv dose of I to bile duct-cannulated rats, 41 and 14% of
      the dose was excreted in bile and urine, respectively. I accounted for 51% of the
      radioactivity in bile and a negligible amount in urine. At 12 hr after iv dosing,
      liver retained 31% of the dose. No accumulation of radioactivity in bone was
      observed. I (3%) and II (6%) were poorly absorbed. Enhanced absorption was
      observed for III (80%) and IV (45%). No I or metabolites of I were found in bile
      or urine of rats dosed with the prodrugs. The structures of two metabolites each
      for I, III, and IV were proposed. Together, they accounted for >80% of the
      radioactivity in urine and approximately 50% of the radioactivity in bile for
      each compound. Metabolism appeared to occur primarily at the farnesyl moiety,
      presumably by the same pathways as for farnesyl-1-pyrophosphate.

PMID- 9763406
TI  - Sulfhydryl-dependent biotransformation and macromolecular binding of 1,2-dibromo
      2,4-dicyanobutane in blood.
AB  - 1,2-Dibromo-2,4-dicyanobutane (BCB) is a broad-spectrum microbicide used
      commercially in consumer products. The objectives of this study were to elucidate
      the biotransformation of BCB, characterize its ability to covalently bind
      macromolecules, and predict the possible toxicological ramifications of such
      events. After iv administration of [14C]BCB to male Fischer 344 rats, 14C
      equivalents were observed to bind gradually to blood constituents. By 48 hr,
      approximately 12% of the total dose was covalently bound. At no time was parent
      compound detected in the blood. However, the debrominated BCB metabolite 2
      methyleneglutaronitrile (MGN) was observed. In vitro experiments revealed that
      BCB was extremely labile and was readily debrominated in fresh whole blood,
      erythrocyte preparations, and buffered glutathione (GSH) solutions. In each case,
      the formation of MGN was inhibited by the alkylation of free sulfhydryls with N
      ethylmaleimide (NEM). For every 1 mol of BCB converted to MGN, 2 mol of GSH were
      oxidized to glutathione disulfide (GSSG) (BCB + 2 GSH --> MGN + GSSG + 2 HBr).
      The oxidation of free sulfhydryls during the conversion of BCB to MGN caused
      erythrocyte hemolysis (EC50 approximately 1 mM) in isolated preparations.
      Hemolysis was increased by coincubation of BCB with NEM (EC50 approximately 0.3
      mM) and was decreased by coincubation with GSH (EC50 > 3 mM). However, MGN did
      not cause hemolysis of erythrocytes, even at concentrations 10-fold higher than
      the EC50 of BCB. In vitro experiments also demonstrated that incubation with
      either BCB or MGN resulted in significant macromolecular binding to the
      erythrocyte fraction of the blood (approximately 80%). Incubation with NEM
      resulted in a significant decrease in binding for both BCB (11.3% bound) and MGN
      (29.5% bound). Because BCB is rapidly debrominated in whole blood, it appears
      that MGN is the reactive species responsible for macromolecular binding. From
      these studies, we conclude that the conversion of BCB to MGN is mediated by a
      free sulfhydryl-dependent biotransformation pathway. Furthermore, BCB
      biotransformation is required for erythrocyte binding, and the consumption of
      free sulfhydryls associated with the biotransformation of BCB is responsible for
      hemolysis.

PMID- 9763407
TI  - Absorption, distribution, metabolism, and excretion of atevirdine in the rat.
AB  - Atevirdine mesylate (U-87201E) is a highly specific nonnucleoside inhibitor of
      human immunodeficiency virus type 1 reverse transcriptase. The absorption,
      metabolism, and excretion of atevirdine were investigated in male and female
      Sprague-Dawley rats after oral administration of nonradiolabeled atevirdine
      mesylate at doses of 20 mg/kg/day or 200 mg/kg/day for 8 days, with
      [14C]atevirdine mesylate single doses of 10 mg/kg or 100 mg/kg on study days 1
      and 10. The distribution of [14C]atevirdine mesylate was also evaluated by whole
      body autoradiography in male and female Sprague-Dawley, pregnant Sprague-Dawley,
      and male Long-Evans rats after a single 10 mg/kg oral dose. Plasma levels of
      atevirdine and its N-desethyl and O-desmethyl metabolites were determined by high
      performance liquid chromatography (HPLC) with ultraviolet detection, urine and
      feces were profiled for atevirdine and metabolites by HPLC with radiochemical
      detection, major metabolites in urine were isolated and identified by nuclear
      magnetic resonance and mass spectrometry, and minor urinary metabolites were
      identified by liquid chromatography/mass spectrometry. Atevirdine was rapidly
      absorbed. The pharmacokinetics of atevirdine were nonlinear. Gender differences
      in the pharmacokinetics and metabolism of atevirdine were observed, consistent
      with the involvement of cytochrome P450 3A. Atevirdine effectively crossed the
      blood-brain barrier and had a high rate of maternal-fetal transfer. At the low
      doses, <2% of the dose was excreted as unchanged parent drug, while atevirdine
      constituted 9%-25% of the dose at the high doses. The metabolism of atevirdine
      was extensive in the rat and involved N-deethylation, O-demethylation,
      hydroxylation at the C-6 position of the indole ring, and hydroxylation of the
      pyridine ring.

PMID- 9763408
TI  - Uroporphyrinogen oxidation catalyzed by human cytochromes P450.
AB  - Porphyria cutanea tarda is associated with excess hepatic production of
      uroporphyrin. Oxidation of uroporphyrinogen to uroporphyrin was previously
      demonstrated to be specifically catalyzed by cytochrome P450 (CYP) 1A2. Here, we
      investigated the ability of human CYP1A2 to catalyze uroporphyrinogen oxidation
      (UROX). UROX activity in human liver microsomes was maximally only 10% of the
      activity in microsomes from livers of untreated mice. There was a poor
      correlation of UROX activity with methoxyresorufin demethylation, an activity
      catalyzed predominantly by CYP1A2 and strongly correlated with immunodetectable
      CYP1A2. With CYP forms expressed in HepG2 cells, the methoxyresorufin
      demethylation and (ethoxyresorufin deethylation) activities of murine and human
      CYP1A2 forms were similar, but UROX activity catalyzed by human CYP1A2 was only
      15-20% of the activity catalyzed by murine CYP1A2. Human CYP1A1, CYP1A2, and
      CYP3A4 expressed in lymphoblastoid cells all catalyzed UROX. In insect cells,
      CYP1A2 was more active in catalyzing UROX than was CYP1A1, CYP2E, CYP3A4, or
      CYP3A5. Human CYP1A2 expressed in Escherichia coli as a fusion protein with rat
      CYP oxidoreductase also catalyzed UROX. Reconstituted human CYP1A2 and CYP3A4
      were active in catalyzing UROX, with reconstituted CYP1A2 having the highest
      specific activity obtained in this study. From inhibitor studies, it was
      concluded that some of the UROX activity in the insect cell microsomes was
      attributable to expressed CYP and some to an unidentified source. These results
      indicate that human CYP1A2 is active in catalyzing UROX but has lower activity
      than the murine orthologue. The results also indicate that most of the UROX
      activity found in human liver microsomes is not due to CYP1A2.

PMID- 9763409
TI  - Catalytic properties of an expressed cytochrome P450 2B1 from a Wistar-Kyoto rat
      liver cDNA library.
AB  - Cytochrome P450 2B1 clones were isolated from a phenobarbital-induced Wistar
      Kyoto (WKY) hepatic cDNA library and were found to contain a Glu-322 --> Val
      substitution, compared with wild-type 2B1 from Sprague-Dawley rats. After
      heterologous expression in Escherichia coli and purification, activities of this
      2B1 E322V variant were determined for ethoxycoumarin and androstenedione. The
      total activities and metabolite profiles did not differ between 2B1 E322V and
      wild-type 2B1 for these substrates. In addition, similar rate constants of
      inactivation were observed with the mechanism-based inactivators chloramphenicol,
      N-(2-p-nitrophenethyl)chlorofluoroacetamide, and 9-ethynylphenanthrene. These
      results suggest that the Glu-322 --> Val alteration in the 2B1 WKY variant does
      not significantly affect 2B1 activity. However, another clone obtained from the
      cDNA library contained two additional substitutions: Val-103 --> Ala and Glu-424 
      -> Lys. As residue 103 is within a predicted substrate recognition site (SRS-1),
      it was of interest to determine whether the Val --> Ala substitution conferred
      any unique catalytic activities on 2B1. No differences in the metabolism of
      ethoxycoumarin or androstenedione were observed. However, the Val-103 --> Ala
      alteration caused an approximately threefold decrease in the rate constant of
      inactivation for 9-ethynylphenanthrene in comparison with either 2B1 E322V or
      wild-type 2B1. Based on computer modeling, residue 103 is predicted to be near
      the active site but at a distance greater than 5A from 9-ethynylphenanthrene. Our
      results suggest that the Val-103 --> Ala alteration may have an indirect
      influence on the susceptibility of P450 2B1 to mechanism-based inactivators.

PMID- 9763410
TI  - Effect of androgen administration during puberty on hepatic CYP2C11, CYP3A, and
      CYP2A1 expression in adult female rats.
AB  - This biochemical and pharmacokinetic investigation was undertaken to evaluate the
      effects of androgen administration during puberty on sex-dependent cytochrome
      P450 (CYP or P450) enzyme expression in adult female rats. Hepatic testosterone
      2alpha-hydroxylase activity and CYP2C11 and CYP3A protein levels were elevated in
      prepubertally ovariectomized rats injected subcutaneously with testosterone
      enanthate at 35-49 days of age and killed 41 days after discontinuation of
      treatment. In contrast, testosterone 6beta- and 7alpha-hydroxylase activities and
      CYP2A1 protein content were not affected. The increase in CYP2C11 and CYP3A was
      likely not due to circulating testosterone because plasma testosterone was
      undetectable. The calculated elimination half-life was 51 +/- 6 hr (mean +/- SE)
      after testosterone enanthate administration. By 80 days after treatment, CYP2C11
      and CYP3A levels were no longer increased. To determine if CYP2C11 expression was
      responsive to a more periodic pattern of androgen release, ovariectomized rats
      were injected subcutaneously once or twice daily with unesterified testosterone
      (elimination half-life was 2.0 +/- 0.3 hr, mean +/- SE). Once- or twice-daily
      dosing (5 or 2.5 micromol/kg/injection, respectively) during days 35-49 of age
      did not increase the mean CYP2C11 expression in 90-day-old female rats, although
      testosterone 2alpha-hydroxylase activity and CYP2C11 protein content were
      elevated in three of the eight rats injected twice daily. Neither dosing regimen
      increased CYP3A or decreased CYP2A1 expression. In summary, the results indicate
      that treatment with testosterone enanthate during puberty resulted in a prolonged
      but reversible increase in hepatic expression of CYP2C11 and CYP3A.

PMID- 9763411
TI  - Immunohistochemical localization of UDP-glucuronosyltransferases in rat brain
      during early development.
AB  - Extrahepatic glucuronidation, such as that in the central nervous system (CNS),
      may play a very important role in xenobiotic disposition and may serve to protect
      the CNS from potentially toxic xenobiotics. UDP-glucuronosyltransferase (UGT) 1A6
      is an important catalyst for phenol and polycyclic aromatic hydrocarbon
      glucuronidation. Studies were designed to determine the immunohistochemical
      localization of UGT1A6 and the steroid-reactive UGTs 2B2 and 2B3 in brain regions
      throughout the rat development. Neuronal cells, such as pyramidal cells, in
      sections from cerebral cortex and hippocampus displayed intensive UGT1A6-specific
      staining. UGT1A6-specific staining was also found in neuronal cells throughout
      the cerebral cortex, as well as in the cerebellar white matter. Glial cells
      revealed no apparent staining. In addition, staining for UGT1A6 was seen in
      choroid plexus at a later developmental stage. Although UGT1A6 staining was
      evident, brain sections analyzed for UGT2B2 and UGT2B3 immunoreactivity showed no
      significant staining. These results provide the first definitive evidence for the
      presence and cellular localization of UGT1A6, in neurons of developing rat brain,
      whereas UGT2B2 and UGT2B3 were not detected.

PMID- 9763413
TI  - Major cytochrome P450 enzyme responsible for oxidation of secondary alcohols to
      the corresponding ketones in mouse hepatic microsomes. Oxidation of 7-hydroxy
      delta8-tetrahydrocannabinol to 7-oxo-delta8-tetrahydrocannabinol.
AB  - The oxidative activities of 7alpha- and 7beta-hydroxy-Delta8-tetrahydrocannabinol
      (7alpha- and 7beta-hydroxy-Delta8-THC) to 7-oxo-Delta8-THC in hepatic microsomes
      of mice were significantly increased by the treatment of mice with dexamethasone
      or phenobarbital. A cytochrome P450 enzyme, named P450MDX-B, was purified from
      hepatic microsomes of dexamethasone-treated mice, and its apparent molecular mass
      was estimated to be 51,000. The NH2-terminal amino acid sequence of P450MDX-B was
      the same as that of CYP3A11. The oxidative activities of 7alpha- and 7beta
      hydroxy-Delta8-THC were 2.55 and 4.92 nmol/min/nmol P450, respectively. The
      antibody against P450MDX-B almost completely inhibited the oxidative activities
      of 7alpha- and 7beta-hydroxy-Delta8-THC in mice. These results indicate that
      P450MDX-B (CYP3A11) is a major enzyme responsible for the oxidation of 7alpha-
      and 7beta-hydroxy-Delta8-THC to 7-oxo-Delta8-THC in mouse liver.

PMID- 9763412
TI  - Regulation of hepatic cytochrome P450 2C11 by transforming growth factor-beta,
      hepatocyte growth factor, and interleukin-11.
AB  - Injection of rats with bacterial lipopolysaccharide down-regulates P450 (P450)
      2C11 (2C11) mRNA to about 20% of its control levels after only 6 hr, and this
      level is maintained for at least 48 hr. Although we and others have demonstrated
      that this effect may be at least partially mediated by the cytokines interleukin
      1, interleukin-6, and tumor necrosis factor-alpha, as well as by glucocorticoids,
      the time courses and potencies of 2C11 repression by each single mediator
      suggested that no cytokine alone is responsible for the entire time course of
      2C11 suppression during inflammation. Here, we show that transforming growth
      factor-beta, hepatocyte growth factor, and interleukin-11 are potent inhibitors
      of 2C11 expression. In all three cases, 0.1 ng/ml was enough to down-regulate
      2C11 mRNA levels to 50% of control. Interleukin-8, a cytokine that is secreted
      during the acute phase response but does not influence the liver acute phase
      response, did not affect 2C11 expression. The various mediators have different
      time courses of 2C11 down-regulation, indicating that the roles of each may be
      different at different phases of the response.

PMID- 9763414
TI  - Human biotransformation of bropirimine. Characterization of the major bropirimine
      oxidative metabolites formed in vitro.
AB  - Bropirimine (2-amino-5-bromo-6-phenyl-4-pyrimidinone) is a member of a class of
      antineoplastic agents known as aryl pyrimidinones. In human liver microsomal
      incubations, bropirimine oxidative metabolism is characterized by the formation
      of three metabolites. Mass spectrometric analysis of the incubation mixture
      revealed three bropirimine oxidative metabolites, identified as the bropirimine
      dihydrodiol, p-hydroxybropirimine, and m-hydroxybropirimine. In vitro studies
      using human liver microsomes and recombinant cytochrome P450 isoforms were
      performed to identify the P450 enzyme(s) responsible for bropirimine oxidation.
      Coincubation with the selective CYP1A2 inhibitor alpha-naphthoflavone abolished
      bropirimine metabolism in human liver microsomes. Furthermore, when screened
      against a panel of cDNA expressed cytochrome P450 enzymes (CYP1A2, CYP2C9,
      CYP2C19, CYP2D6, CYP2E1, and CYP3A4), bropirimine was metabolized to both p- and
      m-hydroxybropirimine exclusively in incubations with cDNA-expressed CYP1A2
      microsomes. Mechanistic studies using cDNA-expressed CYP1A2 microsomes fortified
      with microsomal epoxide hydrolase revealed that all three bropirimine oxidative
      metabolites appear to be the result of a common arene oxide, which serves as a
      substrate for microsomal epoxide hydrolase to generate the dihydrodiol or
      rearranges to yield p- and m-hydroxybropirimine.

PMID- 9763415
TI  - Gene targeting studies begin to reveal the function of neurofilament proteins.

PMID- 9763416
TI  - Transcription sites are not correlated with chromosome territories in wheat
      nuclei.
AB  - We have determined the relationship between overall nuclear architecture,
      chromosome territories, and transcription sites within the nucleus, using three
      dimensional confocal microscopy of well preserved tissue sections of wheat roots.
      Chromosome territories were visualized by GISH using rye genomic probe in
      wheat/rye translocation and addition lines. The chromosomes appeared as elongated
      regions and showed a clear centromere-telomere polarization, with the two
      visualized chromosomes lying approximately parallel to one another across the
      nucleus. Labeling with probes to telomeres and centromeres confirmed a striking
      Rabl configuration in all cells, with a clear clustering of the centromeres, and
      cell files often maintained a common polarity through several division cycles.
      Transcription sites were detected by BrUTP incorporation in unfixed tissue
      sections and revealed a pattern of numerous foci uniformly distributed throughout
      the nucleoplasm, as well as more intensely labeled foci in the nucleoli. It has
      been suggested that the gene-rich regions in wheat chromosomes are clustered
      towards the telomeres. However, we found no indication of a difference in
      concentration of transcription sites between telomere and centromere poles of the
      nucleus. Neither could we detect any evidence that the transcription sites were
      preferentially localized with respect to the chromosome territorial boundaries.

PMID- 9763417
TI  - Large-scale chromosomal movements during interphase progression in Drosophila.
AB  - We examined the effect of cell cycle progression on various levels of chromosome
      organization in Drosophila. Using bromodeoxyuridine incorporation and DNA
      quantitation in combination with fluorescence in situ hybridization, we detected
      gross chromosomal movements in diploid interphase nuclei of larvae. At the onset
      of S-phase, an increased separation was seen between proximal and distal
      positions of a long chromsome arm. Progression through S-phase disrupted
      heterochromatic associations that have been correlated with gene silencing.
      Additionally, we have found that large-scale G1 nuclear architecture is
      continually dynamic. Nuclei display a Rabl configuration for only approximately 2
      h after mitosis, and with further progression of G1-phase can establish
      heterochromatic interactions between distal and proximal parts of the chromosome
      arm. We also find evidence that somatic pairing of homologous chromosomes is
      disrupted during S-phase more rapidly for a euchromatic than for a
      heterochromatic region. Such interphase chromosome movements suggest a possible
      mechanism that links gene regulation via nuclear positioning to the cell cycle:
      delayed maturation of heterochromatin during G1-phase delays establishment of a
      silent chromatin state.

PMID- 9763418
TI  - Mutational analysis of the structure and localization of the nucleolus in the
      yeast Saccharomyces cerevisiae.
AB  - The nucleolus in Saccharomyces cerevisiae is a crescent-shaped structure that
      makes extensive contact with the nuclear envelope. In different chromosomal rDNA
      deletion mutants that we have analyzed, the nucleolus is not organized into a
      crescent structure, as determined by immunofluorescence microscopy, fluorescence
      in situ hybridization, and electron microscopy. A strain carrying a plasmid with
      a single rDNA repeat transcribed by RNA polymerase I (Pol I) contained a
      fragmented nucleolus distributed throughout the nucleus, primarily localized at
      the nuclear periphery. A strain carrying a plasmid with the 35S rRNA coding
      region fused to the GAL7 promoter and transcribed by Pol II contained a rounded
      nucleolus that often lacked extensive contact with the nuclear envelope.
      Ultrastructurally distinct domains were observed within the round nucleolus. A
      similar rounded nucleolar morphology was also observed in strains carrying the
      Pol I plasmid in combination with mutations that affect Pol I function. In a Pol
      I-defective mutant strain that carried copies of the GAL7-35S rDNA fusion gene
      integrated into the chromosomal rDNA locus, the nucleolus exhibited a round
      morphology, but was more closely associated with the nuclear envelope in the form
      of a bulge. Thus, both the organization of the rDNA genes and the type of
      polymerase involved in rDNA expression strongly influence the organization and
      localization of the nucleolus.

PMID- 9763419
TI  - The perinucleolar compartment and transcription.
AB  - The perinucleolar compartment (PNC) is a unique nuclear structure localized at
      the periphery of the nucleolus. Several small RNAs transcribed by RNA polymerase
      III and two hnRNP proteins have been localized in the PNC (Ghetti, A., S. Pinol
      Roma, W.M. Michael, C. Morandi, and G. Dreyfuss. 1992. Nucleic Acids Res. 20:3671
      3678; Matera, A.G., M.R. Frey, K. Margelot, and S.L. Wolin. 1995. J. Cell Biol.
      129:1181- 1193; Timchenko, L.T., J.W. Miller, N.A. Timchenko, D.R. DeVore, K.V.
      Datar, L. Lin, R. Roberts, C.T. Caskey, and M.S. Swanson. 1996. Nucleic Acids
      Res. 24: 4407-4414; Huang, S., T. Deerinck, M.H. Ellisman, and D.L. Spector.
      1997. J. Cell Biol. 137:965-974). In this report, we show that the PNC
      incorporates Br-UTP and FITC-conjugated CTP within 5 min of pulse labeling.
      Selective inhibition of RNA polymerase I does not appreciably affect the
      nucleotide incorporation in the PNC. Inhibition of all RNA polymerases by
      actinomycin D blocks the incorporation completely, suggesting that Br-UTP
      incorporation in the PNC is due to transcription by RNA polymerases II and/or
      III. Treatment of cells with an RNA polymerase II and III inhibitor induces a
      significant reorganization of the PNC. In addition, double labeling experiments
      showed that poly(A) RNA and some of the factors required for pre-mRNA processing
      were localized in the PNC in addition to being distributed in their previously
      characterized nucleoplasmic domains. Fluorescence recovery after photobleaching
      (FRAP) analysis revealed a rapid turnover of polypyrimidine tract binding protein
      within the PNC, demonstrating the dynamic nature of the structure. Together,
      these findings suggest that the PNC is a functional compartment involved in RNA
      metabolism in the cell nucleus.

PMID- 9763420
TI  - Characterization of the kinetochore binding domain of CENP-E reveals interactions
      with the kinetochore proteins CENP-F and hBUBR1.
AB  - We have identified a 350-amino acid domain in the kinetochore motor CENP-E that
      specifies kinetochore binding in mitosis but not during interphase. The
      kinetochore binding domain was used in a yeast two-hybrid screen to isolate
      interacting proteins that included the kinetochore proteins CENP-E, CENP-F, and
      hBUBR1, a BUB1-related kinase that was found to be mutated in some colorectal
      carcinomas (Cahill, D.P., C. Lengauer, J. Yu, G.J. Riggins, J.K. Wilson, S.D.
      Markowitz, K.W. Kinzler, and B. Vogelstein. 1998. Nature. 392:300-303). CENP-F,
      hBUBR1, and CENP-E assembled onto kinetochores in sequential order during late
      stages of the cell cycle. These proteins therefore define discrete steps along
      the kinetochore assembly pathway. Kinetochores of unaligned chromosome exhibited
      stronger hBUBR1 and CENP-E staining than those of aligned chromosomes. CENP-E and
      hBUBR1 remain colocalized at kinetochores until mid-anaphase when hBUBR1
      localized to portions of the spindle midzone that did not overlap with CENP-E. As
      CENP-E and hBUBR1 can coimmunoprecipitate with each other from HeLa cells, they
      may function as a motor-kinase complex at kinetochores. However, the complex
      distribution pattern of hBUBR1 suggests that it may regulate multiple functions
      that include the kinetochore and the spindle midzone.

PMID- 9763421
TI  - Fab1p is essential for PtdIns(3)P 5-kinase activity and the maintenance of
      vacuolar size and membrane homeostasis.
AB  - The Saccharomyces cerevisiae FAB1 gene encodes a 257-kD protein that contains a
      cysteine-rich RING-FYVE domain at its NH2-terminus and a kinase domain at its
      COOH terminus. Based on its sequence, Fab1p was initially proposed to function as
      a phosphatidylinositol 4-phosphate (PtdIns(4)P) 5-kinase (). Additional sequence
      analysis of the Fab1p kinase domain, reveals that Fab1p defines a subfamily of
      putative PtdInsP kinases that is distinct from the kinases that synthesize
      PtdIns(4,5)P2. Consistent with this, we find that unlike wild-type cells,
      fab1Delta, fab1(tsf), and fab1 kinase domain point mutants lack detectable levels
      of PtdIns(3,5)P2, a phosphoinositide recently identified both in yeast and
      mammalian cells. PtdIns(4,5)P2 synthesis, on the other hand, is only moderately
      affected even in fab1Delta mutants. The presence of PtdIns(3)P in fab1 mutants,
      combined with previous data, indicate that PtdIns(3,5)P2 synthesis is a two step
      process, requiring the production of PtdIns(3)P by the Vps34p PtdIns 3-kinase and
      the subsequent Fab1p- dependent phosphorylation of PtdIns(3)P yielding
      PtdIns(3,5)P2. Although Vps34p-mediated synthesis of PtdIns(3)P is required for
      the proper sorting of hydrolases from the Golgi to the vacuole, the production of
      PtdIns(3,5)P2 by Fab1p does not directly affect Golgi to vacuole trafficking,
      suggesting that PtdIns(3,5)P2 has a distinct function. The major phenotypes
      resulting from Fab1p kinase inactivation include temperature-sensitive growth,
      vacuolar acidification defects, and dramatic increases in vacuolar size. Based on
      our studies, we hypothesize that whereas Vps34p is essential for anterograde
      trafficking of membrane and protein cargoes to the vacuole, Fab1p may play an
      important compensatory role in the recycling/turnover of membranes deposited at
      the vacuole. Interestingly, deletion of VAC7 also results in an enlarged vacuole
      morphology and has no detectable PtdIns(3,5)P2, suggesting that Vac7p functions
      as an upstream regulator, perhaps in a complex with Fab1p. We propose that Fab1p
      and Vac7p are components of a signal transduction pathway which functions to
      regulate the efflux or turnover of vacuolar membranes through the regulated
      production of PtdIns(3,5)P2.

PMID- 9763422
TI  - Sorting mechanisms regulating membrane protein traffic in the apical transcytotic
      pathway of polarized MDCK cells.
AB  - The transcytotic pathway followed by the polymeric IgA receptor (pIgR) carrying
      its bound ligand (dIgA) from the basolateral to the apical surface of polarized
      MDCK cells has been mapped using morphological tracers. At 20 degreesC dIgA-pIgR
      internalize to interconnected groups of vacuoles and tubules that comprise the
      endosomal compartment and in which they codistribute with internalized
      transferrin receptors (TR) and epidermal growth factor receptors (EGFR). Upon
      transfer to 37 degreesC the endosome vacuoles develop long tubules that give rise
      to a distinctive population of 100-nm-diam cup-shaped vesicles containing pIgR.
      At the same time, the endosome gives rise to multivesicular endosomes (MVB)
      enriched in EGFR and to 60-nm-diam basolateral vesicles. The cup-shaped vesicles
      carry the dIgA/pIgR complexes to the apical surface where they exocytose. Using
      video microscopy and correlative electron microscopy to study cells grown thin
      and flat we show that endosome vacuoles tubulate in response to dIgA/pIgR but
      that the tubules contain TR as well as pIgR. However, we show that TR are removed
      from these dIgA-induced tubules via clathrin-coated buds and, as a result, the
      cup-shaped vesicles to which the tubules give rise become enriched in dIgA/pIgR.
      Taken together with the published information available on pIgR trafficking
      signals, our observations suggest that the steady-state concentrations of TR and
      unoccupied pIgR on the basolateral surface of polarized MDCK cells are maintained
      by a signal-dependent, clathrin-based sorting mechanism that operates along the
      length of the transcytotic pathway. We propose that the differential sorting of
      occupied receptors within the MDCK endosome is achieved by this clathrin-based
      mechanism continuously retrieving receptors like TR from the pathways that
      deliver pIgR to the apical surface and EGFR to the lysosome.

PMID- 9763423
TI  - An atypical PKC directly associates and colocalizes at the epithelial tight
      junction with ASIP, a mammalian homologue of Caenorhabditis elegans polarity
      protein PAR-3.
AB  - Cell polarity is fundamental to differentiation and function of most cells.
      Studies in mammalian epithelial cells have revealed that the establishment and
      maintenance of cell polarity depends upon cell adhesion, signaling networks, the
      cytoskeleton, and protein transport. Atypical protein kinase C (PKC) isotypes
      PKCzeta and PKClambda have been implicated in signaling through lipid metabolites
      including phosphatidylinositol 3-phosphates, but their physiological role remains
      elusive. In the present study we report the identification of a protein, ASIP
      (atypical PKC isotype-specific interacting protein), that binds to aPKCs, and
      show that it colocalizes with PKClambda to the cell junctional complex in
      cultured epithelial MDCKII cells and rat intestinal epithelia. In addition,
      immunoelectron microscopy revealed that ASIP localizes to tight junctions in
      intestinal epithelial cells. Furthermore, ASIP shows significant sequence
      similarity to Caenorhabditis elegans PAR-3. PAR-3 protein is localized to the
      anterior periphery of the one-cell embryo, and is required for the establishment
      of cell polarity in early embryos. ASIP and PAR-3 share three PDZ domains, and
      can both bind to aPKCs. Taken together, our results suggest a role for a protein
      complex containing ASIP and aPKC in the establishment and/or maintenance of
      epithelial cell polarity. The evolutionary conservation of the protein complex
      and its asymmetric distribution in polarized cells from worm embryo to mammalian
      differentiated cells may mean that the complex functions generally in the
      organization of cellular asymmetry.

PMID- 9763425
TI  - Why are two different cross-linkers necessary for actin bundle formation in vivo
      and what does each cross-link contribute?
AB  - In developing Drosophila bristles two species of cross-linker, the forked
      proteins and fascin, connect adjacent actin filaments into bundles. Bundles form
      in three phases: (a) tiny bundles appear; (b) these bundles aggregate into larger
      bundles; and (c) the filaments become maximally cross-linked by fascin. In
      mutants that completely lack forked, aggregation of the bundles does not occur so
      that the mature bundles consist of <50 filaments versus approximately 700 for
      wild type. If the forked concentration is genetically reduced to half the wild
      type, aggregation of the tiny bundles occurs but the filaments are poorly ordered
      albeit with small patches of fascin cross-linked filaments. In mutants containing
      an excess of forked, all the bundles tend to aggregate and the filaments are
      maximally crossbridged by fascin. Alternatively, if fascin is absent, phases 1
      and 2 occur normally but the resultant bundles are twisted and the filaments
      within them are poorly ordered. By extracting fully elongated bristles with
      potassium iodide which removes fascin but leaves forked, the bundles change from
      being straight to twisted and the filaments within them become poorly ordered.
      From these observations we conclude that (a) forked is used early in development
      to aggregate the tiny bundles into larger bundles; and (b) forked facilitates
      fascin entry into the bundles to maximally cross-link the actin filaments into
      straight, compact, rigid bundles. Thus, forked aligns the filaments and then
      directs fascin binding so that inappropriate cross-linking does not occur.

PMID- 9763424
TI  - Small espin: a third actin-bundling protein and potential forked protein ortholog
      in brush border microvilli.
AB  - An approximately 30-kD isoform of the actin-binding/ bundling protein espin has
      been discovered in the brush borders of absorptive epithelial cells in rat
      intestine and kidney. Small espin is identical in sequence to the COOH terminus
      of the larger ( approximately 110-kD) espin isoform identified in the actin
      bundles of Sertoli cell-spermatid junctional plaques (Bartles, J.R., A. Wierda,
      and L. Zheng. 1996. J. Cell Sci. 109:1229-1239), but it contains two unique
      peptides at its NH2 terminus. Small espin was localized to the parallel actin
      bundles of brush border microvilli, resisted extraction with Triton X-100, and
      accumulated in the brush border during enterocyte differentiation/migration along
      the crypt-villus axis in adults. In transfected BHK fibroblasts, green
      fluorescent protein-small espin decorated F-actin-containing fibers and appeared
      to elicit their accumulation and/or bundling. Recombinant small espin bound to
      skeletal muscle and nonmuscle F-actin with high affinity (Kd = 150 and 50 nM) and
      cross-linked the filaments into bundles. Sedimentation, gel filtration, and
      circular dichroism analyses suggested that recombinant small espin was a monomer
      with an asymmetrical shape and a high percentage of alpha-helix. Deletion
      mutagenesis suggested that small espin contained two actin-binding sites in its
      COOH-terminal 116-amino acid peptide and that the NH2-terminal half of its forked
      homology peptide was necessary for bundling activity.

PMID- 9763426
TI  - Clb5-associated kinase activity is required early in the spindle pathway for
      correct preanaphase nuclear positioning in Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, a single cyclin-dependent kinase, Cdc28, regulates
      both G1/S and G2/M phase transitions by associating with stage-specific cyclins.
      During progression through S phase and G2/M, Cdc28 is activated by the B-type
      cyclins Clb1-6. Because of functional redundancy, specific roles for individual
      Clbs have been difficult to assign. To help genetically define such roles,
      strains carrying a cdc28(ts) allele, combined with single CLB deletions were
      studied. We assumed that by limiting the activity of the kinase, these strains
      would be rendered more sensitive to loss of individual Clbs. By this approach, a
      novel phenotype associated with CLB5 mutation was observed. Homozygous cdc28
      4(ts) clb5 diploids were inviable at room temperature. Cells were defective in
      spindle positioning, leading to migration of undivided nuclei into the bud.
      Occasionally, misplaced spindles were observed in cdc28-4 clb5 haploids;
      additional deletion of CLB6 caused full penetrance. Thus, CLB5 effects proper
      preanaphase spindle positioning, yet the requirement differs in haploids and
      diploids. The execution point for the defect corresponded to the time of Clb5
      dependent kinase activation. Nevertheless, lethality of cdc28-4 clb5 diploids was
      not rescued by CLB2 or CLB4 overexpression, indicating a specificity of Clb5
      function beyond temporality of expression.

PMID- 9763427
TI  - Motile properties of vimentin intermediate filament networks in living cells.
AB  - The motile properties of intermediate filament (IF) networks have been studied in
      living cells expressing vimentin tagged with green fluorescent protein (GFP
      vimentin). In interphase and mitotic cells, GFP-vimentin is incorporated into the
      endogenous IF network, and accurately reports the behavior of IF. Time-lapse
      observations of interphase arrays of vimentin fibrils demonstrate that they are
      constantly changing their configurations in the absence of alterations in cell
      shape. Intersecting points of vimentin fibrils, or foci, frequently move towards
      or away from each other, indicating that the fibrils can lengthen or shorten.
      Fluorescence recovery after photobleaching shows that bleach zones across fibrils
      rapidly recover their fluorescence. During this recovery, bleached zones
      frequently move, indicating translocation of fibrils. Intriguingly, neighboring
      fibrils within a cell can exhibit different rates and directions of movement, and
      they often appear to extend or elongate into the peripheral regions of the
      cytoplasm. In these same regions, short filamentous structures are also seen
      actively translocating. All of these motile properties require energy, and the
      majority appear to be mediated by interactions of IF with microtubules and
      microfilaments.

PMID- 9763428
TI  - Rapid movements of vimentin on microtubule tracks: kinesin-dependent assembly of
      intermediate filament networks.
AB  - The assembly and maintenance of an extended intermediate filament (IF) network in
      fibroblasts requires microtubule (MT) integrity. Using a green fluorescent
      protein-vimentin construct, and spreading BHK-21 cells as a model system to study
      IF-MT interactions, we have discovered a novel mechanism involved in the assembly
      of the vimentin IF cytoskeleton. This entails the rapid, discontinuous, and MT
      dependent movement of IF precursors towards the peripheral regions of the
      cytoplasm where they appear to assemble into short fibrils. These precursors, or
      vimentin dots, move at speeds averaging 0.55 +/- 0.24 micrometer/s. The vimentin
      dots colocalize with MT and their motility is inhibited after treatment with
      nocodazole. Our studies further implicate a conventional kinesin in the movement
      of the vimentin dots. The dots colocalize with conventional kinesin as shown by
      indirect immunofluorescence, and IF preparations from spreading cells are
      enriched in kinesin. Furthermore, microinjection of kinesin antibodies into
      spreading cells prevents the assembly of an extended IF network. These studies
      provide insights into the interactions between the IF and MT systems. They also
      suggest a role for conventional kinesin in the distribution of non-membranous
      protein cargo, and the local regulation of IF assembly.

PMID- 9763430
TI  - Disruption of the NF-H gene increases axonal microtubule content and velocity of
      neurofilament transport: relief of axonopathy resulting from the toxin beta,beta'
      iminodipropionitrile.
AB  - To investigate the role of the neurofilament heavy (NF-H) subunit in neuronal
      function, we generated mice bearing a targeted disruption of the gene coding for
      the NF-H subunit. Surprisingly, the lack of NF-H subunits had little effect on
      axonal calibers and electron microscopy revealed no significant changes in the
      number and packing density of neurofilaments made up of only the neurofilament
      light (NF-L) and neurofilament medium (NF-M) subunits. However, our analysis of
      NF-H knockout mice revealed an approximately 2.4-fold increase of microtubule
      density in their large ventral root axons. This finding was further corroborated
      by a corresponding increase in the ratio of assembled tubulin to NF-L protein in
      insoluble cytoskeletal preparations from the sciatic nerve. Axonal transport
      studies carried out by the injection of [35S]methionine into spinal cord revealed
      an increased transport velocity of newly synthesized NF-L and NF-M proteins in
      motor axons of NF-H knockout mice. When treated with beta,beta'
      iminodipropionitrile (IDPN), a neurotoxin that segregates microtubules and
      retards neurofilament transport, mice heterozygous or homozygous for the NF-H
      null mutation did not develop neurofilamentous swellings in motor neurons, unlike
      normal mouse littermates. These results indicate that the NF-H subunit is a key
      mediator of IDPN-induced axonopathy.

PMID- 9763429
TI  - Neurofilament-dependent radial growth of motor axons and axonal organization of
      neurofilaments does not require the neurofilament heavy subunit (NF-H) or its
      phosphorylation.
AB  - Neurofilaments are essential for establishment and maintenance of axonal diameter
      of large myelinated axons, a property that determines the velocity of electrical
      signal conduction. One prominent model for how neurofilaments specify axonal
      growth is that the 660-amino acid, heavily phosphorylated tail domain of
      neurofilament heavy subunit (NF-H) is responsible for neurofilament-dependent
      structuring of axoplasm through intra-axonal crossbridging between adjacent
      neurofilaments or to other axonal structures. To test such a role, homologous
      recombination was used to generate NF-H-null mice. In peripheral motor and
      sensory axons, absence of NF-H does not significantly affect the number of
      neurofilaments or axonal elongation or targeting, but it does affect the
      efficiency of survival of motor and sensory axons. Loss of NF-H caused only a
      slight reduction in nearest neighbor spacing of neurofilaments and did not affect
      neurofilament distribution in either large- or small-diameter motor axons. Since
      postnatal growth of motor axon caliber continues largely unabated in the absence
      of NF-H, neither interactions mediated by NF-H nor the extensive phosphorylation
      of it within myelinated axonal segments are essential features of this growth.

PMID- 9763431
TI  - Requirement of heavy neurofilament subunit in the development of axons with large
      calibers.
AB  - Neurofilaments (NFs) are prominent components of large myelinated axons. Previous
      studies have suggested that NF number as well as the phosphorylation state of the
      COOH-terminal tail of the heavy neurofilament (NF-H) subunit are major
      determinants of axonal caliber. We created NF-H knockout mice to assess the
      contribution of NF-H to the development of axon size as well as its effect on the
      amounts of low and mid-sized NF subunits (NF-L and NF-M respectively).
      Surprisingly, we found that NF-L levels were reduced only slightly whereas NF-M
      and tubulin proteins were unchanged in NF-H-null mice. However, the calibers of
      both large and small diameter myelinated axons were diminished in NF-H-null mice
      despite the fact that these mice showed only a slight decrease in NF density and
      that filaments in the mutant were most frequently spaced at the same
      interfilament distance found in control. Significantly, large diameter axons
      failed to develop in both the central and peripheral nervous systems. These
      results demonstrate directly that unlike losing the NF-L or NF-M subunits, loss
      of NF-H has only a slight effect on NF number in axons. Yet NF-H plays a major
      role in the development of large diameter axons.

PMID- 9763432
TI  - Regulated targeting of BAX to mitochondria.
AB  - The proapoptotic protein BAX contains a single predicted transmembrane domain at
      its COOH terminus. In unstimulated cells, BAX is located in the cytosol and in
      peripheral association with intracellular membranes including mitochondria, but
      inserts into mitochondrial membranes after a death signal. This failure to insert
      into mitochondrial membrane in the absence of a death signal correlates with
      repression of the transmembrane signal-anchor function of BAX by the NH2-terminal
      domain. Targeting can be instated by deleting the domain or by replacing the BAX
      transmembrane segment with that of BCL-2. In stimulated cells, the contribution
      of the NH2 terminus of BAX correlates with further exposure of this domain after
      membrane insertion of the protein. The peptidyl caspase inhibitor zVAD-fmk partly
      blocks the stimulated mitochondrial membrane insertion of BAX in vivo, which is
      consistent with the ability of apoptotic cell extracts to support mitochondrial
      targeting of BAX in vitro, dependent on activation of caspase(s). Taken together,
      our results suggest that regulated targeting of BAX to mitochondria in response
      to a death signal is mediated by discrete domains within the BAX polypeptide. The
      contribution of one or more caspases may reflect an initiation and/or
      amplification of this regulated targeting.

PMID- 9763433
TI  - Bax-induced cytochrome C release from mitochondria is independent of the
      permeability transition pore but highly dependent on Mg2+ ions.
AB  - Bcl-2 family members either promote or repress programmed cell death. Bax, a
      death-promoting member, is a pore-forming, mitochondria-associated protein whose
      mechanism of action is still unknown. During apoptosis, cytochrome C is released
      from the mitochondria into the cytosol where it binds to APAF-1, a mammalian
      homologue of Ced-4, and participates in the activation of caspases. The release
      of cytochrome C has been postulated to be a consequence of the opening of the
      mitochondrial permeability transition pore (PTP). We now report that Bax is
      sufficient to trigger the release of cytochrome C from isolated mitochondria.
      This pathway is distinct from the previously described calcium-inducible,
      cyclosporin A-sensitive PTP. Rather, the cytochrome C release induced by Bax is
      facilitated by Mg2+ and cannot be blocked by PTP inhibitors. These results
      strongly suggest the existence of two distinct mechanisms leading to cytochrome C
      release: one stimulated by calcium and inhibited by cyclosporin A, the other Bax
      dependent, Mg2+ sensitive but cyclosporin insensitive.

PMID- 9763434
TI  - Transition from caspase-dependent to caspase-independent mechanisms at the onset
      of apoptotic execution.
AB  - We have compared cytoplasmic extracts from chicken DU249 cells at various stages
      along the apoptotic pathway. Extracts from morphologically normal "committed
      stage" cells induce apoptotic morphology and DNA cleavage in substrate nuclei but
      require ongoing caspase activity to do so. In contrast, extracts from frankly
      apoptotic cells induce apoptotic events in added nuclei in a caspase-independent
      manner. Biochemical fractionation of these extracts reveals that a column
      fraction enriched in endogenous active caspases is unable to induce DNA
      fragmentation or chromatin condensation in substrate nuclei, whereas a caspase
      depleted fraction induces both changes. Further characterization of the
      "execution phase" extracts revealed the presence of an ICAD/DFF45 (inhibitor of
      caspase-activated DNase/DNA fragmentation factor)- inhibitable nuclease
      resembling CAD, plus another activity that was required for the apoptotic
      chromatin condensation. Despite the presence of active caspases, committed stage
      extracts lacked these downstream activities, suggesting that the caspases and
      downstream factors are segregated from one another in vivo during the latent
      phase. These observations not only indicate that caspases act in an executive
      fashion, serving to activate downstream factors that disassemble the nucleus
      rather than disassembling it themselves, but they also suggest that activation of
      the downstream factors (rather than the caspases) is the critical event that
      occurs at the transition from the latent to active phase of apoptosis.

PMID- 9763435
TI  - Modulation of calcium current in arteriolar smooth muscle by alphav beta3 and
      alpha5 beta1 integrin ligands.
AB  - Vasoactive effects of soluble matrix proteins and integrin-binding peptides on
      arterioles are mediated by alphav beta3 and alpha5 beta1 integrins. To examine
      the underlying mechanisms, we measured L-type Ca2+ channel current in arteriolar
      smooth muscle cells in response to integrin ligands. Whole-cell, inward Ba2+
      currents were inhibited after application of soluble cyclic RGD peptide,
      vitronectin (VN), fibronectin (FN), either of two anti-beta3 integrin antibodies,
      or monovalent beta3 antibody. With VN or beta3 antibody coated onto microbeads
      and presented as an insoluble ligand, current was also inhibited. In contrast,
      beads coated with FN or alpha5 antibody produced significant enhancement of
      current after bead attachment. Soluble alpha5 antibody had no effect on current
      but blocked the increase in current evoked by FN-coated beads and enhanced
      current when applied in combination with an appropriate IgG. The data suggest
      that alphavbeta3 and alpha5 beta1 integrins are differentially linked through
      intracellular signaling pathways to the L-type Ca2+ channel and thereby alter
      control of Ca2+ influx in vascular smooth muscle. This would account for the
      vasoactive effects of integrin ligands on arterioles and provide a potential
      mechanism for wound recognition during tissue injury.

PMID- 9763436
TI  - Cre-loxP-mediated inactivation of the alpha6A integrin splice variant in vivo:
      evidence for a specific functional role of alpha6A in lymphocyte migration but
      not in heart development.
AB  - Two splice variants of the alpha6 integrin subunit, alpha6A and alpha6B, with
      different cytoplasmic domains, have previously been described. While alpha6B is
      expressed throughout the development of the mouse, the expression of alpha6A
      begins at 8.5 days post coitum and is initially restricted to the myocardium.
      Later in ontogeny, alpha6A is found in various epithelia and in certain cells of
      the immune system. In this study, we have investigated the function of alpha6A in
      vivo by generating knockout mice deficient for this splice variant. The Cre- loxP
      system of the bacteriophage P1 was used to specifically remove the exon encoding
      the cytoplasmic domain of alpha6A in embryonic stem cells, and the deletion
      resulted in the expression of alpha6B in all tissues that normally express
      alpha6A. We show that alpha6A-/- mice develop normally and are fertile. The
      substitution of alpha6A by alpha6B does not impair the development and function
      of the heart, hemidesmosome formation in the epidermis, or keratinocyte
      migration. Furthermore, T cells differentiated normally in alpha6A-/- mice.
      However, the substitution of alpha6A by alpha6B leads to a decrease in the
      migration of lymphocytes through laminin-coated Transwell filters and to a
      reduction of the number of T cells isolated from the peripheral and mesenteric
      lymph nodes. Lymphocyte homing to the lymph nodes, which involves various types
      of integrin-ligand interactions, was not affected in the alpha6A knockout mice,
      indicating that the reduced number of lymph node cells could not be directly
      attributed to defects in lymphocyte trafficking. Nevertheless, the expression of
      alpha6A might be necessary for optimal lymphocyte migration on laminin in certain
      pathological conditions.

PMID- 9763439
TI  - Use of a beta1 integrin-deficient human T cell to identify beta1 integrin
      cytoplasmic domain sequences critical for integrin function.
AB  - T cell activation rapidly and transiently regulates the functional activity of
      integrin receptors. Stimulation of CD3/T cell receptor, CD2 or CD28, as well as
      activation with phorbol esters, can induce within minutes an increase in beta1
      integrin-mediated adhesion of T cells to fibronectin. In this study, we have
      produced and utilized a mutant of the Jurkat T cell line, designated A1, that
      lacks protein and mRNA expression of the beta1 integrin subunit but retains
      normal levels of CD2, CD3, and CD28 on the cell surface. Activation-dependent
      adhesion of A1 cells to fibronectin could be restored upon transfection of a wild
      type human beta1 integrin cDNA. Adhesion induced by phorbol 12-myristate 13
      acetate-, CD3-, CD2-, and CD28 stimulation did not occur if the carboxy-terminal
      five amino acids of the beta1 tail were truncated or if either of two well
      conserved NPXY motifs were deleted. Scanning alanine substitutions of the carboxy
      terminal five amino acids demonstrated a critical role for the tyrosine residue
      at position 795. The carboxy-terminal truncation and the NPXY deletions also
      reduced adhesion induced by direct stimulation of the beta1 integrin with the
      activating beta1 integrin-specific mAb TS2/16, although the effects were not as
      dramatic as observed with the other integrin-activating signals. These results
      demonstrate a vital role for the amino-terminal NPXY motif and the carboxy
      terminal end of the beta1 integrin cytoplasmic domain in activation-dependent
      regulation of integrin-mediated adhesion in T cells. Furthermore, the A1 cell
      line represents a valuable new cellular reagent for the analysis of beta1
      integrin structure and function in human T cells.

PMID- 9763437
TI  - Fibronectin matrix regulates activation of RHO and CDC42 GTPases and cell cycle
      progression.
AB  - Adherent cells assemble fibronectin into a fibrillar matrix on their apical
      surface. The fibril formation is initiated by fibronectin binding to the
      integrins alpha5 beta1 and alphav beta3, and is completed by a process that
      includes fibronectin self-assembly. We found that a 76- amino acid fragment of
      fibronectin (III1-C) that forms one of the self-assembly sites caused disassembly
      of preformed fibronectin matrix without affecting cell adhesion. Treating
      attached fibroblasts or endothelial cells with III1-C inhibited cell migration
      and proliferation. Rho-dependent stress fiber formation and Rho-dependent focal
      contact protein phosphorylation were also inhibited, whereas Cdc42 was activated,
      leading to actin polymerization into filopodia. ACK (activated Cdc42-binding
      kinase) and p38 MAPK (mitogen-activated protein kinase), two downstream effectors
      of Cdc42, were activated, whereas PAK (p21-activated kinase) and JNK/SAPK (c-Jun
      NH2-terminal kinase/ stress-activated protein kinase) were inhibited. III1-C
      treatment also modulated activation of JNK and ERK (extracellular signal
      regulated kinases) in response to growth factors, and reduced the activity of the
      cyclin E-cdk2 complex. These results indicate that the absence of fibronectin
      matrix causes activation of Cdc42, and that fibronectin matrix is required for
      Rho activation and cell cycle progression.

PMID- 9763438
TI  - In vitro reconstitution of microtubule plus end-directed, GTPgammaS-sensitive
      motility of Golgi membranes.
AB  - Purified Golgi membranes were mixed with cytosol and microtubules (MTs) and
      observed by video enhanced light microscopy. Initially, the membranes appeared as
      vesicles that moved along MTs. As time progressed, vesicles formed aggregates
      from which membrane tubules emerged, traveled along MTs, and eventually generated
      extensive reticular networks. Membrane motility required ATP, occurred mainly
      toward MT plus ends, and was inhibited almost completely by the H1 monoclonal
      antibody to kinesin heavy chain, 5'-adenylylimidodiphosphate, and 100 microM but
      not 20 microM vanadate. Motility was also blocked by GTPgammaS or A1F4- but was
      insensitive to A1C13, NaF, staurosporin, or okadaic acid. The targets for
      GTPgammaS and A1F4- were evidently of cytosolic origin, did not include kinesin
      or MTs, and were insensitive to several probes for trimeric G proteins. Transport
      of Golgi membranes along MTs mediated by a kinesin has thus been reconstituted in
      vitro. The motility is regulated by one or more cytosolic GTPases but not by
      protein kinases or phosphatases that are inhibited by staurosporin or okadaic
      acid, respectively. The pertinent GTPases are likely to be small G proteins or
      possibly dynamin. The in vitro motility may correspond to Golgi-to-ER or Golgi-to
      cell surface transport in vivo.

PMID- 9763441
TI  - The role of topoisomerase II in meiotic chromosome condensation and segregation
      in Schizosaccharomyces pombe.
AB  - Topoisomerase II is able to break and rejoin double-strand DNA. It controls the
      topological state and forms and resolves knots and catenanes. Not much is known
      about the relation between the chromosome segregation and condensation defects as
      found in yeast top2 mutants and the role of topoisomerase II in meiosis. We
      studied meiosis in a heat-sensitive top2 mutant of Schizosaccharomyces pombe.
      Topoisomerase II is not required until shortly before meiosis I. The enzyme is
      necessary for condensation shortly before the first meiotic division but not for
      early meiotic prophase condensation. DNA replication, prophase morphology, and
      dynamics of the linear elements are normal in the top2 mutant. The top2 cells are
      not able to perform meiosis I. Arrested cells have four spindle pole bodies and
      two spindles but only one nucleus, suggesting that the arrest is nonregulatory.
      Finally, we show that the arrest is partly solved in a top2 rec7 double mutant,
      indicating that topoisomerase II functions in the segregation of recombined
      chromosomes. We suggest that the inability to decatenate the replicated DNA is
      the primary defect in top2. This leads to a loss of chromatin condensation
      shortly before meiosis I, failure of sister chromatid separation, and a
      nonregulatory arrest.

PMID- 9763440
TI  - The role of glucosidase I (Cwh41p) in the biosynthesis of cell wall beta-1,6
      glucan is indirect.
AB  - CWH41, a gene involved in the assembly of cell wall beta-1,6-glucan, has recently
      been shown to be the structural gene for Saccharomyces cerevisiae glucosidase I
      that is responsible for initiating the trimming of terminal alpha-1,2-glucose
      residue in the N-glycan processing pathway. To distinguish between a direct or
      indirect role of Cwh41p in the biosynthesis of beta-1,6-glucan, we constructed a
      double mutant, alg5Delta (lacking dolichol-P-glucose synthase) cwh41Delta, and
      found that it has the same phenotype as the alg5Delta single mutant. It contains
      wild-type levels of cell wall beta-1,6-glucan, shows moderate underglycosylation
      of N-linked glycoproteins, and grows at concentrations of Calcofluor White (which
      interferes with cell wall assembly) that are lethal to cwh41Delta single mutant.
      The strong genetic interactions of CWH41 with KRE6 and KRE1, two other genes
      involved in the beta-1,6-glucan biosynthetic pathway, disappear in the absence of
      dolichol-P-glucose synthase (alg5Delta). The triple mutant
      alg5Deltacwh41Deltakre6Delta is viable, whereas the double mutant
      cwh41Deltakre6Delta in the same genetic background is not. The severe slow growth
      phenotype and 75% reduction in cell wall beta-1,6-glucan, characteristic of the
      cwh41Deltakre1Delta double mutant, are not observed in the triple mutant
      alg5Deltacwh41Deltakre1Delta. Kre6p, a putative Golgi glucan synthase, is
      unstable in cwh41Delta strains, and its overexpression renders these cells
      Calcofluor White resistant. These results demonstrate that the role of
      glucosidase I (Cwh41p) in the biosynthesis of cell wall beta-1,6-glucan is
      indirect and that dolichol-P-glucose is not an intermediate in this pathway.

PMID- 9763443
TI  - Ste6p mutants defective in exit from the endoplasmic reticulum (ER) reveal
      aspects of an ER quality control pathway in Saccharomyces cerevisiae.
AB  - We are studying the intracellular trafficking of the multispanning membrane
      protein Ste6p, the a-factor transporter in Saccharomyces cerevisiae and a member
      of the ATP-binding cassette superfamily of proteins. In the present study, we
      have used Ste6p as model for studying the process of endoplasmic reticulum (ER)
      quality control, about which relatively little is known in yeast. We have
      identified three mutant forms of Ste6p that are aberrantly ER retained, as
      determined by immunofluorescence and subcellular fractionation. By pulse-chase
      metabolic labeling, we demonstrate that these mutants define two distinct
      classes. The single member of Class I, Ste6-166p, is highly unstable. We show
      that its degradation involves the ubiquitin-proteasome system, as indicated by
      its in vivo stabilization in certain ubiquitin-proteasome mutants or when cells
      are treated with the proteasome inhibitor drug MG132. The two Class II mutant
      proteins, Ste6-13p and Ste6-90p, are hyperstable relative to wild-type Ste6p and
      accumulate in the ER membrane. This represents the first report of a single
      protein in yeast for which distinct mutant forms can be channeled to different
      outcomes by the ER quality control system. We propose that these two classes of
      ER-retained Ste6p mutants may define distinct checkpoint steps in a linear
      pathway of ER quality control in yeast. In addition, a screen for high-copy
      suppressors of the mating defect of one of the ER-retained ste6 mutants has
      identified a proteasome subunit, Hrd2p/p97, previously implicated in the
      regulated degradation of wild-type hydroxymethylglutaryl-CoA reductase in the ER
      membrane.

PMID- 9763442
TI  - Highly stoichiometric, stable, and specific association of integrin alpha3beta1
      with CD151 provides a major link to phosphatidylinositol 4-kinase, and may
      regulate cell migration.
AB  - Here we describe an association between alpha3beta1 integrin and transmembrane-4
      superfamily (TM4SF) protein CD151. This association is maintained in relatively
      stringent detergents and thus is remarkably stable in comparison with previously
      reported integrin-TM4SF protein associations. Also, the association is highly
      specific (i.e., observed in vitro in absence of any other cell surface proteins),
      and highly stoichiometric (nearly 90% of alpha3beta1 associated with CD151). In
      addition, alpha3beta1 and CD151 appeared in parallel on many cell lines and
      showed nearly identical skin staining patterns. Compared with other integrins,
      alpha3beta1 exhibited a considerably higher level of associated
      phosphatidylinositol-4-kinase (PtdIns 4-kinase) activity, most of which was
      removed upon immunodepletion of CD151. Specificity for CD151 and PtdIns 4-kinase
      association resided in the extracellular domain of alpha3beta1, thus establishing
      a novel paradigm for the specific recruitment of an intracellular signaling
      molecule. Finally, antibodies to either CD151 or alpha3beta1 caused a
      approximately 88-92% reduction in neutrophil motility in response to f-Met-Leu
      Phe on fibronectin, suggesting an functionally important role of these complexes
      in cell migration.

PMID- 9763444
TI  - Fibroblast growth factor (FGF) soluble receptor 1 acts as a natural inhibitor of
      FGF2 neurotrophic activity during retinal degeneration.
AB  - Fibroblast growth factors (FGF) 1 and 2 and their tyrosine kinase receptor (FGFR)
      are present throughout the adult retina. FGFs are potential mitogens, but adult
      retinal cells are maintained in a nonproliferative state unless the retina is
      damaged. Our work aims to find a modulator of FGF signaling in normal and
      pathological retina. We identified and sequenced a truncated FGFR1 form from rat
      retina generated by the use of selective polyadenylation sites. This 70-kDa form
      of soluble extracellular FGFR1 (SR1) was distributed mainly localized in the
      inner nuclear layer of the retina, whereas the full-length FGFR1 form was
      detected in the retinal Muller glial cells. FGF2 and FGFR1 mRNA levels greatly
      increased in light-induced retinal degeneration. FGFR1 was detected in the radial
      fibers of activated retinal Muller glial cells. In contrast, SR1 mRNA synthesis
      followed a biphasic pattern of down- and up-regulation, and anti-SR1 staining was
      intense in retinal pigmented epithelial cells. The synthesis of SR1 and FGFR1
      specifically and independently regulated in normal and degenerating retina
      suggests that changes in the proportion of various FGFR forms may control the
      bioavailability of FGFs and thus their potential as neurotrophic factors. This
      was demonstrated in vivo during retinal degeneration when recombinant SR1
      inhibited the neurotrophic activity of exogenous FGF2 and increased damaging
      effects of light by inhibiting endogenous FGF. This study highlights the
      significance of the generation of SR1 in normal and pathological conditions.

PMID- 9763445
TI  - A late mitotic regulatory network controlling cyclin destruction in Saccharomyces
      cerevisiae.
AB  - Exit from mitosis requires the inactivation of mitotic cyclin-dependent kinase
      cyclin complexes, primarily by ubiquitin-dependent cyclin proteolysis. Cyclin
      destruction is regulated by a ubiquitin ligase known as the anaphase-promoting
      complex (APC). In the budding yeast Saccharomyces cerevisiae, members of a large
      class of late mitotic mutants, including cdc15, cdc5, cdc14, dbf2, and tem1,
      arrest in anaphase with a phenotype similar to that of cells expressing
      nondegradable forms of mitotic cyclins. We addressed the possibility that the
      products of these genes are components of a regulatory network that governs
      cyclin proteolysis. We identified a complex array of genetic interactions among
      these mutants and found that the growth defect in most of the mutants is
      suppressed by overexpression of SPO12, YAK1, and SIC1 and is exacerbated by
      overproduction of the mitotic cyclin Clb2. When arrested in late mitosis, the
      mutants exhibit a defect in cyclin-specific APC activity that is accompanied by
      high Clb2 levels and low levels of the anaphase inhibitor Pds1. Mutant cells
      arrested in G1 contain normal APC activity. We conclude that Cdc15, Cdc5, Cdc14,
      Dbf2, and Tem1 cooperate in the activation of the APC in late mitosis but are not
      required for maintenance of that activity in G1.

PMID- 9763447
TI  - cut11(+): A gene required for cell cycle-dependent spindle pole body anchoring in
      the nuclear envelope and bipolar spindle formation in Schizosaccharomyces pombe.
AB  - The "cut" mutants of Schizosaccharomyces pombe are defective in spindle formation
      and/or chromosome segregation, but they proceed through the cell cycle, resulting
      in lethality. Analysis of temperature-sensitive alleles of cut11(+) suggests that
      this gene is required for the formation of a functional bipolar spindle.
      Defective spindle structure was revealed with fluorescent probes for tubulin and
      DNA. Three-dimensional reconstruction of mutant spindles by serial sectioning and
      electron microscopy showed that the spindle pole bodies (SPBs) either failed to
      complete normal duplication or were free floating in the nucleoplasm.
      Localization of Cut11p tagged with the green fluorescent protein showed punctate
      nuclear envelope staining throughout the cell cycle and SPBs staining from early
      prophase to mid anaphase. This SPB localization correlates with the time in the
      cell cycle when SPBs are inserted into the nuclear envelope. Immunoelectron
      microscopy confirmed the localization of Cut11p to mitotic SPBs and nuclear pore
      complexes. Cloning and sequencing showed that cut11(+) encodes a novel protein
      with seven putative membrane-spanning domains and homology to the Saccharomyces
      cerevisiae gene NDC1. These data suggest that Cut11p associates with nuclear pore
      complexes and mitotic SPBs as an anchor in the nuclear envelope; this role is
      essential for mitosis.

PMID- 9763446
TI  - Identification of regulators for Ypt1 GTPase nucleotide cycling.
AB  - Small GTPases of the Ypt/Rab family are involved in the regulation of vesicular
      transport. Cycling between the GDP- and GTP-bound forms and the accessory
      proteins that regulate this cycling are thought to be crucial for Ypt/Rab
      function. Guanine nucleotide exchange factors (GEFs) stimulate both GDP loss and
      GTP uptake, and GTPase-activating proteins (GAPs) stimulate GTP hydrolysis.
      Little is known about GEFs and GAPs for Ypt/Rab proteins. In this article we
      report the identification and initial characterization of two factors that
      regulate nucleotide cycling by Ypt1p, which is essential for the first two steps
      of the yeast secretory pathway. The Ypt1p-GEF stimulates GDP release and GTP
      uptake at least 10-fold and is specific for Ypt1p. Partially purified Ypt1p-GEF
      can rescue the inhibition caused by the dominant-negative Ypt1p-D124N mutant of
      in vitro endoplasmic reticulum-to-Golgi transport. This mutant probably blocks
      transport by inhibiting the GEF, suggesting that we have identified the
      physiological GEF for Ypt1p. The Ypt1p-GAP stimulates GTP hydrolysis by Ypt1p up
      to 54-fold, has a higher affinity for the GTP-bound form of Ypt1p than for the
      GDP-bound form, and is specific to a subgroup of exocytic Ypt proteins. The Ypt1p
      GAP activity is not affected by deletion of two genes that encode known Ypt GAPs,
      GYP7 and GYP1, nor is it influenced by mutations in SEC18, SEC17, or SEC22, genes
      whose products are involved in vesicle fusion. The GEF and GAP activities for
      Ypt1p localize to particulate cellular fractions. However, contrary to the
      predictions of current models, the GEF activity localizes to the fraction that
      functions as the acceptor in an endoplasmic reticulum-to-Golgi transport assay,
      whereas the GAP activity cofractionates with markers for the donor. On the basis
      of our current and previous results, we propose a new model for the role of
      Ypt/Rab nucleotide cycling and the factors that regulate this process.

PMID- 9763448
TI  - The dynamic behavior of individual microtubules associated with chromosomes in
      vitro.
AB  - Mitotic movements of chromosomes are usually coupled to the elongation and
      shortening of the microtubules to which they are bound. The lengths of
      kinetochore-associated microtubules change by incorporation or loss of tubulin
      subunits, principally at their chromosome-bound ends. We have reproduced aspects
      of this phenomenon in vitro, using a real-time assay that displays directly the
      movements of individual chromosome-associated microtubules as they elongate and
      shorten. Chromosomes isolated from cultured Chinese hamster ovary cells were
      adhered to coverslips and then allowed to bind labeled microtubules. In the
      presence of tubulin and GTP, these microtubules could grow at their chromosome
      bound ends, causing the labeled segments to move away from the chromosomes, even
      in the absence of ATP. Sometimes a microtubule would switch to shortening,
      causing the direction of movement to change abruptly. The link between a
      microtubule and a chromosome was mechanically strong; 15 pN of tension was
      generally insufficient to detach a microtubule, even though it could add subunits
      at the kinetochore-microtubule junction. The behavior of the microtubules in
      vitro was regulated by the chromosomes to which they were bound; the frequency of
      transitions from polymerization to depolymerization was decreased, and the speed
      of depolymerization-coupled movement toward chromosomes was only one-fifth the
      rate of shortening for microtubules free in solution. Our results are consistent
      with a model in which each microtubule interacts with an increasing number of
      chromosome-associated binding sites as it approaches the kinetochore.

PMID- 9763449
TI  - A yeast t-SNARE involved in endocytosis.
AB  - The ORF YOL018c (TLG2) of Saccharomyces cerevisiae encodes a protein that belongs
      to the syntaxin protein family. The proteins of this family, t-SNAREs, are
      present on target organelles and are thought to participate in the specific
      interaction between vesicles and acceptor membranes in intracellular membrane
      trafficking. TLG2 is not an essential gene, and its deletion does not cause
      defects in the secretory pathway. However, its deletion in cells lacking the
      vacuolar ATPase subunit Vma2p leads to loss of viability, suggesting that Tlg2p
      is involved in endocytosis. In tlg2Delta cells, internalization was normal for
      two endocytic markers, the pheromone alpha-factor and the plasma membrane uracil
      permease. In contrast, degradation of alpha-factor and uracil permease was
      delayed in tlg2Delta cells. Internalization of positively charged Nanogold shows
      that the endocytic pathway is perturbed in the mutant, which accumulates Nanogold
      in primary endocytic vesicles and shows a greatly reduced complement of early
      endosomes. These results strongly suggest that Tlg2p is a t-SNARE involved in
      early endosome biogenesis.

PMID- 9763450
TI  - Overexpression of a novel rho family GTPase, RacC, induces unusual actin-based
      structures and positively affects phagocytosis in Dictyostelium discoideum.
AB  - Rho family proteins have been implicated in regulating various cellular
      processes, including actin cytoskeleton organization, endocytosis, cell cycle,
      and gene expression. In this study, we analyzed the function of a novel
      Dictyostelium discoideum Rho family protein (RacC). A cell line was generated
      that conditionally overexpressed wild-type RacC three- to fourfold relative to
      endogenous RacC. Light and scanning electron microscopy indicated that the
      morphology of the RacC-overexpressing cells [RacC WT(+) cells] was significantly
      altered compared with control cells. In contrast to the cortical F-actin
      distribution normally observed, RacC WT(+) cells displayed unusual dorsal and
      peripheral F-actin-rich surface blebs (petalopodia, for flower-like).
      Furthermore, phagocytosis in the RacC WT(+) cells was induced threefold relative
      to control Ax2 cells, whereas fluid-phase pinocytosis was reduced threefold,
      primarily as the result of an inhibition of macropinocytosis. Efflux of fluid
      phase markers was also reduced in the RacC WT(+) cells, suggesting that RacC may
      regulate postinternalization steps along the endolysosomal pathway. Treatment of
      cells with Wortmannin and LY294002 (phosphatidylinositol 3-kinase inhibitors)
      prevented the RacC-induced morphological changes but did not affect phagocytosis,
      suggesting that petalopodia are probably not required for RacC-induced
      phagocytosis. In contrast, inactivating diacylglycerol-binding motif-containing
      proteins by treating cells with the drug calphostin C completely inhibited
      phagocytosis in control and RacC WT(+) cells. These results suggest that RacC
      plays a role in actin cytoskeleton organization and phagocytosis in
      Dictyostelium.

PMID- 9763451
TI  - Activation and cellular localization of the cyclosporine A-sensitive
      transcription factor NF-AT in skeletal muscle cells.
AB  - The widely used immunosuppressant cyclosporine A (CSA) blocks nuclear
      translocation of the transcription factor, NF-AT (nuclear factor of activated T
      cells), preventing its activity. mRNA for several NF-AT isoforms has been shown
      to exist in cells outside of the immune system, suggesting a possible mechanism
      for side effects associated with CSA treatment. In this study, we demonstrate
      that CSA inhibits biochemical and morphological differentiation of skeletal
      muscle cells while having a minimal effect on proliferation. Furthermore, in vivo
      treatment with CSA inhibits muscle regeneration after induced trauma in mice.
      These results suggest a role for NF-AT-mediated transcription outside of the
      immune system. In subsequent experiments, we examined the activation and cellular
      localization of NF-AT in skeletal muscle cells in vitro. Known pharmacological
      inducers of NF-AT in lymphoid cells also stimulate transcription from an NF-AT
      responsive reporter gene in muscle cells. Three isoforms of NF-AT (NF-ATp, c, and
      4/x/c3) are present in the cytoplasm of muscle cells at all stages of myogenesis
      tested. However, each isoform undergoes calcium-induced nuclear translocation
      from the cytoplasm at specific stages of muscle differentiation, suggesting
      specificity among NF-AT isoforms in gene regulation. Strikingly, one isoform (NF
      ATc) can preferentially translocate to a subset of nuclei within a single
      multinucleated myotube. These results demonstrate that skeletal muscle cells
      express functionally active NF-AT proteins and that the nuclear translocation of
      individual NF-AT isoforms, which is essential for the ability to coordinate gene
      expression, is influenced markedly by the differentiation state of the muscle
      cell.

PMID- 9763452
TI  - A mutation in a novel yeast proteasomal gene, RPN11/MPR1, produces a cell cycle
      arrest, overreplication of nuclear and mitochondrial DNA, and an altered
      mitochondrial morphology.
AB  - We report here the functional characterization of an essential Saccharomyces
      cerevisiae gene, MPR1, coding for a regulatory proteasomal subunit for which the
      name Rpn11p has been proposed. For this study we made use of the mpr1-1 mutation
      that causes the following pleiotropic defects. At 24 degreesC growth is delayed
      on glucose and impaired on glycerol, whereas no growth is seen at 36 degreesC on
      either carbon source. Microscopic observation of cells growing on glucose at 24
      degreesC shows that most of them bear a large bud, whereas mitochondrial
      morphology is profoundly altered. A shift to the nonpermissive temperature
      produces aberrant elongated cell morphologies, whereas the nucleus fails to
      divide. Flow cytometry profiles after the shift to the nonpermissive temperature
      indicate overreplication of both nuclear and mitochondrial DNA. Consistently with
      the identification of Mpr1p with a proteasomal subunit, the mutation is
      complemented by the human POH1 proteasomal gene. Moreover, the mpr1-1 mutant
      grown to stationary phase accumulates ubiquitinated proteins. Localization of the
      Rpn11p/Mpr1p protein has been studied by green fluorescent protein fusion, and
      the fusion protein has been found to be mainly associated to cytoplasmic
      structures. For the first time, a proteasomal mutation has also revealed an
      associated mitochondrial phenotype. We actually showed, by the use of [rho
      degrees] cells derived from the mutant, that the increase in DNA content per cell
      is due in part to an increase in the amount of mitochondrial DNA. Moreover,
      microscopy of mpr1-1 cells grown on glucose showed that multiple punctate
      mitochondrial structures were present in place of the tubular network found in
      the wild-type strain. These data strongly suggest that mpr1-1 is a valuable tool
      with which to study the possible roles of proteasomal function in mitochondrial
      biogenesis.

PMID- 9763453
TI  - Chemotactic peptide-induced changes of intermediate filament organization in
      neutrophils during granule secretion: role of cyclic guanosine monophosphate.
AB  - In neutrophils activated to secrete with formyl-methionyl-leucyl-phenylalanine,
      intermediate filaments are phosphorylated transiently by cyclic guanosine
      monophosphate (cGMP)-dependent protein kinase (G-kinase). cGMP regulation of
      vimentin organization was investigated. During granule secretion, cGMP levels
      were elevated and intermediate filaments were transiently assembled at the
      pericortex to areas devoid of granules and microfilaments. Microtubule and
      microfilament inhibitors affected intermediate filament organization, granule
      secretion, and cGMP levels. Cytochalasin D and nocodazole caused intermediate
      filaments to assemble at the nucleus, rather than at the pericortex. cGMP levels
      were elevated in neutrophils by both inhibitors; however, with cytochalasin D,
      cGMP was elevated earlier and granule secretion was excessive. Nocodazole did not
      affect normal cGMP elevations, but specific granule secretion was delayed.
      LY83583, a guanylyl cyclase antagonist, inhibited granule secretion and
      intermediate filament organization, but not microtubule or microfilament
      organization. Intermediate filament assembly at the pericortex and secretion were
      partially restored by 8-bromo-cGMP in LY83583-treated neutrophils, suggesting
      that cGMP regulates these functions. G-kinase directly induced intermediate
      filament assembly in situ, and protein phosphatase 1 disassembled filaments.
      However, in intact cells stimulated with formyl-methionyl-leucyl-phenylalanine,
      intermediate filament assembly is focal and transient, suggesting that vimentin
      phosphorylation is compartmentalized. We propose that, in addition to changes in
      microfilament and microtubule organization, granule secretion is also accompanied
      by changes in intermediate filament organization, and that cGMP regulates
      vimentin filament organization via activation of G-kinase.

PMID- 9763454
TI  - Selection of gbeta subunits with point mutations that fail to activate specific
      signaling pathways in vivo: dissecting cellular responses mediated by a
      heterotrimeric G protein in Dictyostelium discoideum.
AB  - In Dictyostelium discoideum, a unique Gbeta subunit is required for a G protein
      coupled receptor system that mediates a variety of cellular responses. Binding of
      cAMP to cAR1, the receptor linked to the G protein G2, triggers a cascade of
      responses, including activation of adenylyl cyclase, gene induction, actin
      polymerization, and chemotaxis. Null mutations of the cAR1, Galpha2, and Gbeta
      genes completely impair all these responses. To dissect specificity in Gbetagamma
      signaling to downstream effectors in living cells, we screened a randomly
      mutagenized library of Gbeta genes and isolated Gbeta alleles that lacked the
      capacity to activate some effectors but retained the ability to regulate others.
      These mutant Gbeta subunits were able to link cAR1 to G2, to support gene
      expression, and to mediate cAMP-induced actin polymerization, and some were able
      to mediate to chemotaxis toward cAMP. None was able to activate adenylyl cyclase,
      and some did not support chemotaxis. Thus, we separated in vivo functions of
      Gbetagamma by making point mutations on Gbeta. Using the structure of the
      heterotrimeric G protein displayed in the computer program CHAIN, we examined the
      positions and the molecular interactions of the amino acids substituted in each
      of the mutant Gbetas and analyzed the possible effects of each replacement. We
      identified several residues that are crucial for activation of the adenylyl
      cyclase. These residues formed an area that overlaps but is not identical to
      regions where bovine Gtbetagamma interacts with its regulators, Galpha and
      phosducin.

PMID- 9763455
TI  - The cytoplasmic zinc finger protein ZPR1 accumulates in the nucleolus of
      proliferating cells.
AB  - The zinc finger protein ZPR1 translocates from the cytoplasm to the nucleus after
      treatment of cells with mitogens. The function of nuclear ZPR1 has not been
      defined. Here we demonstrate that ZPR1 accumulates in the nucleolus of
      proliferating cells. The role of ZPR1 was examined using a gene disruption
      strategy. Cells lacking ZPR1 are not viable. Biochemical analysis demonstrated
      that the loss of ZPR1 caused disruption of nucleolar function, including
      preribosomal RNA expression. These data establish ZPR1 as an essential protein
      that is required for normal nucleolar function in proliferating cells.

PMID- 9763456
TI  - Nucleolar localization elements of Xenopus laevis U3 small nucleolar RNA.
AB  - The Nucleolar Localization Elements (NoLEs) of Xenopus laevis U3 small nucleolar
      RNA (snoRNA) have been defined. Fluorescein-labeled wild-type U3 snoRNA injected
      into Xenopus oocyte nuclei localized specifically to nucleoli as shown by
      fluorescence microscopy. Injection of mutated U3 snoRNA revealed that the 5'
      region containing Boxes A and A', known to be important for rRNA processing, is
      not essential for nucleolar localization. Nucleolar localization of U3 snoRNA was
      independent of the presence and nature of the 5' cap and the terminal stem. In
      contrast, Boxes C and D, common to the Box C/D snoRNA family, are critical
      elements for U3 localization. Mutation of the hinge region, Box B, or Box C' led
      to reduced U3 nucleolar localization. Results of competition experiments
      suggested that Boxes C and D act in a cooperative manner. It is proposed that Box
      B facilitates U3 snoRNA nucleolar localization by the primary NoLEs (Boxes C and
      D), with the hinge region of U3 subsequently base pairing to the external
      transcribed spacer of pre-rRNA, thus positioning U3 snoRNA for its roles in rRNA
      processing.

PMID- 9763458
TI  - Functional and molecular differences between voltage-gated K+ channels of fast
      spiking interneurons and pyramidal neurons of rat hippocampus.
AB  - We have examined gating and pharmacological characteristics of somatic K+
      channels in fast-spiking interneurons and regularly spiking principal neurons of
      hippocampal slices. In nucleated patches isolated from basket cells of the
      dentate gyrus, a fast delayed rectifier K+ current component that was highly
      sensitive to tetraethylammonium (TEA) and 4-aminopyridine (4-AP) (half-maximal
      inhibitory concentrations <0.1 mM) predominated, contributing an average of 58%
      to the total K+ current in these cells. By contrast, in pyramidal neurons of the
      CA1 region a rapidly inactivating A-type K+ current component that was TEA
      resistant prevailed, contributing 61% to the total K+ current. Both types of
      neurons also showed small amounts of the K+ current component mainly found in the
      other type of neuron and, in addition, a slow delayed rectifier K+ current
      component with intermediate properties (slow inactivation, intermediate
      sensitivity to TEA). Single-cell RT-PCR analysis of mRNA revealed that Kv3
      (Kv3.1, Kv3.2) subunit transcripts were expressed in almost all (89%) of the
      interneurons but only in 17% of the pyramidal neurons. In contrast, Kv4 (Kv4.2,
      Kv4.3) subunit mRNAs were present in 87% of pyramidal neurons but only in 55% of
      interneurons. Selective block of fast delayed rectifier K+ channels, presumably
      assembled from Kv3 subunits, by 4-AP reduced substantially the action potential
      frequency in interneurons. These results indicate that the differential
      expression of Kv3 and Kv4 subunits shapes the action potential phenotypes of
      principal neurons and interneurons in the cortex.

PMID- 9763457
TI  - Coilin can form a complex with the U7 small nuclear ribonucleoprotein.
AB  - Coiled bodies (CBs) in the amphibian oocyte nucleus are spherical structures up
      to 10 microm or more in diameter, much larger than their somatic counterparts,
      which rarely exceed 1 microm. Oocyte CBs may have smaller granules attached to
      their surface or embedded within them, which are identical in structure and
      composition to the many hundreds of B-snurposomes found free in the nucleoplasm.
      The matrix of the CBs contains the diagnostic protein p80-coilin, which is
      colocalized with the U7 small nuclear ribonucleoprotein (snRNP), whereas the
      attached and embedded B-snurposomes contain splicing snRNPs. A few of the 50-100
      CBs in the oocyte nucleus are attached to lampbrush chromosomes at the histone
      gene loci. By coimmunoprecipitation we show that coilin and the U7 snRNP can form
      a weak but specific complex in the nucleoplasm, which is dependent on the special
      U7 Sm-binding site. Under the same conditions coilin does not associate with the
      U1 and U2 snRNPs. Coilin is a nucleic acid-binding protein, as shown by its
      interaction with single-stranded DNA and with poly r(U) and poly r(G). We suggest
      that an important function of coilin is to form a transient complex with the U7
      snRNP and accompany it to the CBs. In the case of CBs attached to chromosomes at
      the histone gene loci, the U7 snRNP is thus brought close to the actual site of
      histone pre-mRNA transcription.

PMID- 9763459
TI  - Electrochemical analysis of protein nitrotyrosine and dityrosine in the Alzheimer
      brain indicates region-specific accumulation.
AB  - HPLC with electrochemical array detection (HPLC-ECD) was used to quantify 3,3'
      dityrosine (diTyr) and 3-nitrotyrosine (3-NO2-Tyr) in four regions of the human
      brain that are differentially affected in Alzheimer's disease (AD). DiTyr and 3
      NO2-Tyr levels were elevated consistently in the hippocampus and neocortical
      regions of the AD brain and in ventricular cerebrospinal fluid (VF), reaching
      quantities five- to eightfold greater than mean concentrations in brain and VF of
      cognitively normal subjects. Uric acid, a proposed peroxynitrite scavenger, was
      decreased globally in the AD brain and VF. The results suggest that AD
      pathogenesis may involve the activation of oxidant-producing inflammatory enzyme
      systems, including nitric oxide synthase.

PMID- 9763460
TI  - Postsynaptic mechanisms underlying responsiveness of amygdaloid neurons to
      nociceptin/orphanin FQ.
AB  - Effects of nociceptin/orphanin FQ (N/OFQ), the endogenous ligand of the opioid
      like orphan receptor (ORL), were investigated in the rat lateral (AL) and central
      (ACe) amygdala in vitro. Approximately 98% of presumed projection neurons in the
      AL responded to N/OFQ with an increase in inwardly rectifying potassium
      conductance, resulting in an impairment in cell excitability. Half-maximal
      effects were obtained at 30.6 nM; the Hill coefficient was 0.63. In the ACe, 31%
      of the cells displayed responses similar to that in the AL, 44% were
      nonresponsive, and 25% responded with a small potassium current with a linear
      current-voltage relationship. Responses to N/OFQ were reduced by 100 microM Ba2+,
      were insensitive to 10 microM naloxone, and were blocked by a selective ORL
      antagonist, [Phe1psi(CH2-NH)Gly2]NC(1-13)NH2 (IC50 = 760 nM). Involvement of G
      proteins was indicated by irreversible effects and blockade of action of N/OFQ
      during intracellular presence of GTP-gamma-S (100 microM) and GDP-beta-S (2 mM),
      respectively, and prevention of responses after incubation in pertussis toxin
      (500 ng/ml). These mechanisms may contribute to the role of N/OFQ in the
      reduction of fear responsiveness and stress that have recently been suggested on
      the basis of histochemical and behavioral studies.

PMID- 9763461
TI  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyride neurotoxicity is attenuated in mice
      overexpressing Bcl-2.
AB  - The proto-oncogene Bcl-2 rescues cells from a wide variety of insults. Recent
      evidence suggests that Bcl-2 protects against free radicals and that it increases
      mitochondrial calcium-buffering capacity. The neurotoxicity of 1-methyl-4-phenyl
      1,2,3, 6-tetrahydropyride (MPTP) is thought to involve both mitochondrial
      dysfunction and free radical generation. We therefore investigated MPTP
      neurotoxicity in both Bcl-2 overexpressing mice and littermate controls. MPTP
      induced depletion of dopamine and loss of [3H]mazindol binding were significantly
      attenuated in Bcl-2 overexpressing mice. Protection was more profound with an
      acute dosing regimen than with daily MPTP administration over 5 d. 1-Methyl-4
      phenylpyridinium (MPP+) levels after MPTP administration were similar in Bcl-2
      overexpressing mice and littermates. Bcl-2 blocked MPP+-induced activation of
      caspases. MPTP-induced increases in free 3-nitrotyrosine levels were blocked in
      Bcl-2 overexpressing mice. These results indicate that Bcl-2 overexpression
      protects against MPTP neurotoxicity by mechanisms that may involve both
      antioxidant activity and inhibition of apoptotic pathways.

PMID- 9763462
TI  - Neurotransmitter activation of inwardly rectifying potassium current in
      dissociated hippocampal CA3 neurons: interactions among multiple receptors.
AB  - We characterized potassium current activated by G-protein-coupled receptors in
      acutely dissociated hippocampal CA3 neurons. Agonists for serotonin, adenosine,
      and somatostatin receptors reliably activated a potassium-selective conductance
      that was inwardly rectifying and that was blocked by 1 mM external Ba2+. The
      conductance had identical properties to that activated by GABAB receptors in the
      same cells. In one-half of the CA3 neurons that were tested, the metabotropic
      glutamate agonist 1S,3R-ACPD also activated inwardly rectifying Ba2+-sensitive
      potassium current. Activation of the current by serotonin and adenosine agonists
      occurred with a time constant of 200-700 msec after a lag of 50-100 msec; on
      removal of agonist the current deactivated with a time constant of 1-2 sec after
      a lag of 200-400 msec. These kinetics are similar to GABAB-activated current and
      consistent with a direct action of G-protein on the channels. For somatostatin,
      both activation and deactivation were approximately fourfold slower, probably
      limited by agonist binding and unbinding. The half-maximally effective agonist
      concentrations were approximately 75 nM for somatostatin, approximately 100 nM
      for serotonin, and approximately 400 nM for 2-chloroadenosine. Dose-response
      relationships had Hill coefficients of 1.2-1.9, suggesting cooperativity in the
      receptor-to-channel coupling mechanism. At saturating concentrations of agonists,
      the combined application of baclofen and either somatostatin, serotonin, or 2
      chloroadenosine produced effects that were subadditive and often completely
      occlusive. However, at subsaturating concentrations the effects of baclofen and 2
      chloroadenosine were supra-additive. Thus, low levels of different transmitters
      can act synergistically in activating inwardly rectifying potassium current.

PMID- 9763463
TI  - Regulation of tyrosine hydroxylase gene expression during transdifferentiation of
      striatal neurons: changes in transcription factors binding the AP-1 site.
AB  - We have shown previously that the synergistic interaction of acidic fibroblast
      growth factor (aFGF) and a coactivator (dopamine, protein kinase A, or protein
      kinase C activator) will induce the novel expression of tyrosine hydroxylase (TH)
      in neurons of the developing striatum. In this study we sought to determine
      whether, concomitant with TH expression, there were unique changes in
      transcription factors binding the AP-1 regulatory element on the TH gene. Indeed,
      we found a significant recruitment of proteins into TH-AP-1 complexes as well as
      a shift from low- to high-affinity binding. Supershift experiments further
      revealed dramatic changes in the proteins comprising the AP-1 complexes,
      including recruitment of the transcriptional activators c-Fos, a novel Fos
      protein, Fos-B, and Jun-D. Concomitantly, there was a decrease in repressor-type
      factors ATF-2 and CREM-1. aFGF appeared to play a central but insufficient role,
      requiring the further participation of at least one of the coactivating
      substances. Experiments examining the signal transduction pathway involved in
      mediating these nuclear events demonstrated that the presence of only an FGF (1,
      2, 4, 9) competent to induce TH caused the phosphorylation of mitogen-activated
      protein kinase (MAPK). Moreover, the treatment of cells with MEK/ERK inhibitors
      (apigenin or PD98059) eliminated TH expression and the associated AP-1 changes,
      suggesting that MAPK was a critical mediator of these events. We conclude that,
      during transdifferentiation, signals may be transmitted via MAPK to the TH-AP-1
      site to increase activators and reduce repressors, helping to shift the balance
      in favor of TH gene expression at this and possibly other important regulatory
      sites on the gene.

PMID- 9763464
TI  - Activity-dependent modulation of glutamate receptors by polyamines.
AB  - The mechanisms by which polyamines block AMPA and kainate receptors are not well
      understood, but it has been generally assumed that they act as open-channel
      blockers. Consistent with this, voltage-jump relaxation analysis of GluR6
      equilibrium responses to domoate could be well fit, assuming that spermine,
      spermidine, and philanthotoxin are weakly permeable open-channel blockers.
      Analysis of rate constants for binding and dissociation of polyamines indicated
      that the voltage dependence of block arose primarily from changes in koff rather
      than kon. Experiments with changes in Na concentration further indicate that the
      voltage dependence of polyamine block was governed by ion flux via open channels.
      However, responses to 1 msec applications of L-Glu revealed slow voltage
      dependent rise-times, suggesting that polyamines additionally bind to closed
      states. A kinetic model, which included closed-channel block, reproduced these
      observations but required that polyamines accelerate channel closure either
      through an allosteric mechanism or by emptying the pore of permeant ions.
      Simulations with this model reveal that polyamine block confers novel activity
      dependent regulation on calcium-permeable AMPA and kainate receptor responses.

PMID- 9763465
TI  - Staurosporine-induced apoptosis of cultured rat hippocampal neurons involves
      caspase-1-like proteases as upstream initiators and increased production of
      superoxide as a main downstream effector.
AB  - We induced apoptosis in cultured rat hippocampal neurons by exposure to the
      protein kinase inhibitor staurosporine (30 nM, 24 hr). Treatment with the
      antioxidant (+/-)-alpha-tocopherol (100 microM) or the superoxide dismutase
      mimetic manganese tetrakis (4-benzoyl acid) porphyrin (1 microM) significantly
      reduced staurosporine-induced cell death. Using hydroethidine-based digital
      videomicroscopy, we observed a significant increase in intracellular superoxide
      production that peaked 6-8 hr into the staurosporine exposure. This increase
      occurred in the absence of gross mitochondrial depolarization monitored with the
      voltage-sensitive probe tetramethylrhodamine ethyl ester. We then prepared
      extracts from staurosporine-treated hippocampal neurons and monitored cleavage of
      acetyl-Tyr-Val-Ala-Asp-aminomethyl-coumarin and acetyl-Asp-Glu-Val-Asp-AMC,
      fluorogenic substrates for caspase-1-like and caspase-3-like proteases,
      respectively. Staurosporine caused a significant increase in caspase-1-like
      activity that preceded intracellular superoxide production and reached a maximum
      after 30 min. Caspase-3-like activity paralleled intracellular superoxide
      production, with peak activity seen after 8 hr. Treatment with the corresponding
      caspase-3-like protease inhibitor acetyl-Asp-Glu-Val-Asp-aldehyde (10 microM)
      prevented the increase in caspase-3-like activity and staurosporine-induced
      nuclear fragmentation, but failed to prevent the rise in superoxide production
      and subsequent cell death. In contrast, treatment with caspase-1-like protease
      inhibitors reduced both superoxide production and cell death. Of note,
      antioxidants prevented superoxide production, caspase-3-like protease activity,
      and cell death even when added 4 hr after the onset of the staurosporine
      exposure. These results suggest a scenario of an early, caspase-1-like activity
      followed by a delayed intracellular superoxide production that mediates
      staurosporine-induced cell death of cultured rat hippocampal neurons.

PMID- 9763466
TI  - Two distinct nicotinic receptors, one pharmacologically similar to the vertebrate
      alpha7-containing receptor, mediate Cl currents in aplysia neurons.
AB  - Ionotropic, nicotinic receptors have previously been shown to mediate both
      inhibitory (Cl-dependent) and excitatory (cationic) cholinergic responses in
      Aplysia neurons. We have used fast perfusion methods of agonist and antagonist
      application to reevaluate the effects on these receptors of a wide variety of
      cholinergic compounds, including a number of recently isolated and/or synthesized
      alpha toxins [alpha-conotoxin (alphaCTx)] from Conus snails. These toxins have
      been shown in previous studies to discriminate between the many types of
      nicotinic receptors now known to be expressed in vertebrate muscle,
      neuroendocrine, and neuronal cells. One of these toxins (alphaCTx ImI from the
      worm-eating snail Conus imperialis) revealed that two kinetically and
      pharmacologically distinct elements underlie the ACh-induced Cl-dependent
      response in Aplysia neurons: one element is a rapidly desensitizing current that
      is blocked by the toxin; the other is a slowly desensitizing current that is
      unaffected by the toxin. The two kinetically defined elements were also found to
      be differentially sensitive to different agonists. Finally, the proportion of the
      rapidly desensitizing element to the sustained element was found to be cell
      specific. These observations led to the conclusion that two distinct nicotinic
      receptors mediate Cl currents in Aplysia neurons. The receptor mediating the
      rapidly desensitizing Cl-dependent response shows a strong pharmacological
      resemblance to the vertebrate alpha-bungarotoxin-sensitive, alpha7-containing
      receptor, which is permeable to calcium and mediates a rapidly desensitizing
      excitatory response.

PMID- 9763468
TI  - Synaptic potentials mediated via alpha-bungarotoxin-sensitive nicotinic
      acetylcholine receptors in rat hippocampal interneurons.
AB  - Exogenous application of acetylcholine elicits inward currents in hippocampal
      interneurons that are mediated via alpha-bungarotoxin-sensitive nicotinic
      acetylcholine receptors, but synaptic responses mediated via such receptors have
      never been reported in mammalian brain. In the present study, EPSCs were evoked
      in hippocampal interneurons in rat brain slices by electrical stimulation and
      were recorded by using whole-cell voltage-clamp techniques. Nicotinic EPSCs were
      isolated pharmacologically, using antagonists to block other known types of
      ligand-gated ion channels, and then were tested with either alpha-bungarotoxin or
      methyllycaconitine, which are selective antagonists for nicotinic acetylcholine
      receptors that contain the alpha7 receptor subunit. Each antagonist proved highly
      effective at reducing the remaining synaptic current. Evoked alpha7-mediated
      nicotinic EPSCs also were desensitized by superfusion with 1 microM nicotine, had
      extrapolated reversal potentials near 0 mV, and showed strong inward
      rectification at positive potentials. In several interneurons, methyllycaconitine
      sensitive spontaneous EPSCs also were observed that exhibited a biphasic decay
      rate very similar to that of the alpha7-mediated evoked response. These studies
      provide the first demonstration of a functional cholinergic synapse in the
      mammalian brain, in which the primary postsynaptic receptors are alpha
      bungarotoxin-sensitive nicotinic acetylcholine receptors.

PMID- 9763469
TI  - Induction of NF-kappaB activity during haloperidol-induced oxidative toxicity in
      clonal hippocampal cells: suppression of NF-kappaB and neuroprotection by
      antioxidants.
AB  - Haloperidol (HP), a dopamine receptor antagonist, is cytotoxic to mouse clonal
      hippocampal HT22 cells in a concentration-dependent manner and causes cell death
      by oxidative stress. The addition of HP to HT22 cells led to an increase in
      intracellular peroxides and a time-dependent drop in the intracellular
      glutathione levels. HP-induced oxidative cell death was prevented by the pineal
      hormone melatonin, its precursor N-acetyl serotonin, and most effectively by
      vitamin E (alpha-tocopherol). These antioxidants inhibited the intracellular
      peroxide accumulation and stabilized the glutathione content of HT22 cells after
      the challenge with HP. At the molecular level, HP specifically induced the DNA
      binding activity and the transcriptional activity of the redox-sensitive
      transcription factor NF-kappaB. This enhanced NF-kappaB activity could be blocked
      by the neuroprotective antioxidants. The specific suppression of NF-kappaB by its
      inhibitor IkappaBalpha partially protected the cells against HP, indicating that
      the activation of NF-kappaB may be involved in HP-induced oxidative cell death in
      vitro.

PMID- 9763467
TI  - Delayed release of neurotransmitter from cerebellar granule cells.
AB  - At fast chemical synapses the rapid release of neurotransmitter that occurs
      within a few milliseconds of an action potential is followed by a more sustained
      elevation of release probability, known as delayed release. Here we characterize
      the role of calcium in delayed release and test the hypothesis that facilitation
      and delayed release share a common mechanism. Synapses between cerebellar granule
      cells and their postsynaptic targets, stellate cells and Purkinje cells, were
      studied in rat brain slices. Presynaptic calcium transients were measured with
      calcium-sensitive fluorophores, and delayed release was detected with whole-cell
      recordings. Calcium influx, presynaptic calcium dynamics, and the number of
      stimulus pulses were altered to assess their effect on delayed release and
      facilitation. Following single stimuli, delayed release can be separated into two
      components: one lasting for tens of milliseconds that is steeply calcium
      dependent, the other lasting for hundreds of milliseconds that is driven by low
      levels of calcium with a nearly linear calcium dependence. The amplitude, calcium
      dependence, and magnitude of delayed release do not correspond to those of
      facilitation, indicating that these processes are not simple reflections of a
      shared mechanism. The steep calcium dependence of delayed release, combined with
      the large calcium transients observed in these presynaptic terminals, suggests
      that for physiological conditions delayed release provides a way for cells to
      influence their postsynaptic targets long after their own action potential
      activity has subsided.

PMID- 9763470
TI  - Noradrenergic-specific transcription of the dopamine beta-hydroxylase gene
      requires synergy of multiple cis-acting elements including at least two Phox2a
      binding sites.
AB  - Dopamine beta-hydroxylase (DBH) catalyzes the conversion of dopamine to
      noradrenaline and is selectively expressed in noradrenergic and adrenergic
      neurons and neuroendocrine cells. Recent data from this laboratory showed that a
      paired-like homeodomain (HD) protein, Phox2a, interacts with the HD-binding site
      residing within a composite promoter of the human DBH gene, designated domain IV,
      in a cell-specific manner and directly controls noradrenergic-specific DBH
      promoter activity. In this report, we demonstrate that three additional protein
      binding sites (i.e., domains I, II, and III) between domain IV and the TATA box
      are critical for intact DBH promoter activity in noradrenergic cells and that
      they activate DBH transcription in a highly concerted manner. Transient
      transfection assays of mutant DBH reporter constructs indicated that domain I was
      active in every cell line tested, whereas domain III was preferentially active in
      DBH-positive cells. Remarkably, mutation of domain II was associated with
      inactivation of DBH promoter activity exclusively in DBH-positive cell lines,
      defining it as another noradrenergic-specific promoter element. The cell-specific
      profile of the promoter function of these sequence motifs was further supported
      by in vitro DNA-binding studies and Southwestern analysis. Furthermore,
      competition and antibody supershift assays show that transcription factors Sp1
      and AP2 are the cognate nuclear factors interacting with domains I and III,
      respectively. Parallel evidence indicates that domain II is another Phox2a
      binding site, demonstrating at least two binding sites for this factor in the
      upstream DBH promoter. Strikingly, four tandem copies of domain II increased the
      promoter activity of a minimal DBH promoter by 100- to 200-fold in DBH-positive
      cell lines without compromising cell specificity. Cotransfection of Phox2a
      expression vector dramatically increased the activity of the multiple domain II
      promoter only in DBH-negative cell lines, confirming that domain II is responsive
      to Phox2a. Collectively, this study emphasizes a critical role of Phox2a as well
      as its functional synergism with other transcription factors (e.g., CREB, AP2,
      and Sp1) in transcriptional activation of the DBH gene.

PMID- 9763471
TI  - The endogenous calcium buffer and the time course of transducer adaptation in
      auditory hair cells.
AB  - Mechanoelectrical transducer currents in turtle auditory hair cells adapt to
      maintained stimuli via a Ca2+-dependent mechanism that is sensitive to the level
      of internal calcium buffer. We have used the properties of transducer adaptation
      to compare the effects of exogenous calcium buffers in the patch electrode
      solution with those of the endogenous buffer assayed with perforated-patch
      recording. The endogenous buffer of the hair bundle was equivalent to 0.1-0.4 mM
      BAPTA and, in a majority of cells, supported adaptation in an external Ca2+
      concentration of 70 microM similar to that in turtle endolymph. The endogenous
      buffer had a higher effective concentration, and the adaptation time constant was
      faster in cells at the high-frequency end than at the low-frequency end of the
      cochlea. Experiments using buffers with different Ca2+-binding rates or
      dissociation constants indicated that the speed of adaptation and the resting
      open probability of the transducer channels could be differentially regulated and
      imply that the endogenous buffer must be a fast, high-affinity buffer. In some
      hair cells, the transducer current did not decay exponentially during a sustained
      stimulus but displayed damped oscillations at a frequency (58-230 Hz) that
      depended on external Ca2+ concentration. The gradient in adaptation time constant
      and the tuned transducer current at physiological levels of calcium buffer and
      external Ca2+ suggest that transducer adaptation may contribute to hair cell
      frequency selectivity. The results are discussed in terms of feedback regulation
      of transducer channels mediated by Ca2+ binding at two intracellular sites.

PMID- 9763472
TI  - Axonal injury alters alternative splicing of the retinal NR1 receptor: the
      preferential expression of the NR1b isoforms is crucial for retinal ganglion cell
      survival.
AB  - Cellular-specific splicing of the retinal NMDAR1 receptor (NR1) and expression of
      NMDAR2 receptor (NR2) subunits in response to optic nerve injury was investigated
      by in situ hybridization in adult rats. A controlled optic nerve crush led to a
      clear alteration in the expression of alternatively spliced NR1 variants in the
      retinal ganglion cell layer (GCL). The NR1-2b and NR1-4b isoforms were
      preferentially expressed between 2 d and 1 week after injury, whereas expression
      for all other isoforms remained either unchanged or decreased to barely
      detectable levels within 4 weeks. Cellular silver grain density for NR2 subunits
      also declined in the GCL after trauma. To directly test the hypothesis that NR1b
      expression is crucial for cell survival after axonal trauma, we administered
      intraocularly an antisense oligonucleotide against the NR1b isoform 2 and 3 d
      after injury. This led to a drastic loss of retrogradely labeled retinal ganglion
      cells (RGCs). Antisense targeting clearly reduced retinal NR1 protein levels, as
      judged by Western blot analysis, but had no effect on the cell number in control
      retinas. These findings point toward injury-specific changes in alternative
      splicing of the NR1 receptor, which are crucial for the survival of RGCs after
      partial axonal trauma. We therefore propose that this reflects an adaptive,
      rather than a pathogenic, cellular response to neurotrauma.

PMID- 9763473
TI  - Overexpression of SOD1 in transgenic rats protects vulnerable neurons against
      ischemic damage after global cerebral ischemia and reperfusion.
AB  - Transient global cerebral ischemia resulting from cardiac arrest is known to
      cause selective death in vulnerable neurons, including hippocampal CA1 pyramidal
      neurons. It is postulated that oxygen radicals, superoxide in particular, are
      involved in cell death processes. To test this hypothesis, we first used in situ
      imaging of superoxide radical distribution by hydroethidine oxidation in
      vulnerable neurons. We then generated SOD1 transgenic (Tg) rats with a five-fold
      increase in copper zinc superoxide dismutase activity. The Tg rats and their non
      Tg wild-type littermates were subjected to 10 min of global ischemia followed by
      1 and 3 d of reperfusion. Neuronal damage, as assessed by cresyl violet staining
      and DNA fragmentation analysis, was significantly reduced in the hippocampal CA1
      region, cortex, striatum, and thalamus in SOD1 Tg rats at 3 d, as compared with
      the non-Tg littermates. There were no changes in the hippocampal CA3 subregion
      and dentate gyrus, resistant areas in both SOD1 Tg and non-Tg rats. Quantitative
      analysis of the damaged CA1 subregion showed marked neuroprotection against
      transient global cerebral ischemia in SOD1 Tg rats. These results suggest that
      superoxide radicals play a role in the delayed ischemic death of hippocampal CA1
      neurons. Our data also indicate that SOD1 Tg rats are useful tools for studying
      the role of oxygen radicals in the pathogenesis of neuronal death after transient
      global cerebral ischemia.

PMID- 9763474
TI  - Three-dimensional structure and composition of CA3-->CA1 axons in rat hippocampal
      slices: implications for presynaptic connectivity and compartmentalization.
AB  - Physiological studies of CA3-->CA1 synaptic transmission and plasticity have
      revealed both pre- and postsynaptic effects. Understanding the extent to which
      individual presynaptic axonal boutons could provide local compartments for
      control of synaptic efficacy and microconnectivity requires knowledge of their
      three-dimensional morphology and composition. In hippocampal slices, serial
      electron microscopy was used to examine a nearly homogeneous population of CA3-
      >CA1 axons in the middle of stratum radiatum of area CA1. The locations of
      postsynaptic densities (PSDs), vesicles, and mitochondria were determined along
      75 axon segments (9.1 +/- 2.0 micrometer in length). Synapses, defined by the
      colocalization of PSDs and vesicles, occurred on average at 2.7 micrometer
      intervals along the axons. Most varicosities (68%) had one PSD, 19% had 2-4 PSDs,
      and 13% had none. Synaptic vesicles occurred in 90% of the varicosities. One-half
      (53%) of the varicosities lacked mitochondria, raising questions about their
      regulation of ATP and Ca2+, and 8% of varicosities contained only mitochondria.
      Eleven axons were reconstructed fully. The varicosities were oblong and varied
      greatly in both length (1.1 +/- 0.7 micrometer) and volume (0.13 +/- 0.14
      micrometer 3), whereas the intervaricosity shafts were narrow, tubular, and
      similar in diameter (0.17 +/- 0.04 micrometer) but variable in length (1.4 +/-
      1.2 micrometer). The narrow axonal shafts resemble dendritic spine necks and thus
      could promote biochemical compartmentalization of individual axonal varicosities.
      The findings raise the intriguing possibility of localized differences in
      metabolism and connectivity among different axons, varicosities, and synapses.

PMID- 9763475
TI  - Protease inhibitor coinfusion with amyloid beta-protein results in enhanced
      deposition and toxicity in rat brain.
AB  - Amyloid beta-protein, Abeta, is normally produced in brain and is cleared by
      unknown mechanisms. In Alzheimer's disease (AD), Abeta accumulates in plaque-like
      deposits and is implicated genetically in neurodegeneration. Here we investigate
      mechanisms for Abeta degradation and Abeta toxicity in vivo, focusing on the
      effects of Abeta40, which is the peptide that accumulates in apolipoprotein E4
      associated AD. Chronic intraventricular infusion of Abeta40 into rat brain
      resulted in limited deposition and toxicity. Coinfusion of Abeta40 with the
      cysteine protease inhibitor leupeptin resulted in increased extracellular and
      intracellular Abeta immunoreactivity. Analysis of gliosis and TUNEL in neuron
      layers of the frontal and entorhinal cortex suggested that leupeptin exacerbated
      Abeta40 toxicity. This was supported further by the neuronal staining of
      cathepsin B in endosomes or lysosomes, colocalizing with intracellular Abeta
      immunoreactivity in pyknotic cells. Leupeptin plus Abeta40 caused limited but
      significant neuronal phospho-tau immunostaining in the entorhinal cortex.
      Intriguingly, Abeta40 plus leupeptin induced intracellular accumulation of the
      more toxic Abeta, Abeta42, in a small group of septal neurons. Leupeptin infusion
      previously has been reported to interfere with lysosomal proteolysis and to
      result in the accumulation of lipofuscin, dystrophic neurites, tau- and ubiquitin
      positive inclusions, and structures resembling paired helical filaments.
      Coinfusion of Abeta40 with the serine protease inhibitor aprotinin also increased
      diffuse extracellular deposition but reduced astrocytosis and TUNEL and was not
      associated with intracellular Abeta staining. Collectively, these data suggest
      that an age or Alzheimer's-related defect in lysosomal/endosomal function could
      promote Abeta deposition and DNA fragmentation in neurons and glia similar to
      that found in Alzheimer's disease.

PMID- 9763476
TI  - An early phase of embryonic Dlx5 expression defines the rostral boundary of the
      neural plate.
AB  - Relatively little is known about the molecular events that specify the
      rostrocaudal axis of the neural plate. Here we show that a member of the Distal
      less (Dlx) homeobox gene family, Dlx5, is one of the earliest known markers for
      the most rostral ectoderm, before the formation of an overt neural plate. During
      late gastrulation Dlx5 expression becomes localized to the anterior neural ridge,
      which defines the rostral boundary of the neural plate, and also extends
      caudolaterally, marking the region of the presumptive neural crest. Subsequently,
      Dlx5 is expressed in tissues (olfactory epithelium, ventral cephalic epithelium)
      that are believed to derive from the anterior neural ridge, based on the avian
      fate map. The early phase of Dlx5 expression in the anterior neural ridge and its
      derivatives is distinct from a later phase of expression in the ventral
      telencephalon and diencephalon and also appears to be unique for Dlx5 among
      members of the Dlx family. Another distinctive feature of Dlx5 expression is the
      occurrence of an alternative transcript (deltaDlx5), which encodes a truncated
      protein lacking the homeodomain, and represents a significant fraction of total
      Dlx5 transcripts at all embryonic stages that were examined. In contrast with
      full-length DLX5, the deltaDLX5 truncated protein is deficient in DNA-binding
      activity and does not interact with the homeoprotein partner MSX1. Taken
      together, our findings suggest that Dlx5 activity may be regulated via the
      expression of an alternative transcript and demonstrate that Dlx5 marks the
      anterior boundary of the neural plate.

PMID- 9763477
TI  - Multiple restricted origin of oligodendrocytes.
AB  - The plp gene encodes the proteolipid protein and its alternatively spliced
      product DM-20, major proteins of CNS myelin. In the mouse, plp/dm-20 transcripts
      are expressed beginning at embryonic day 9.5 (E9.5) by restricted foci of
      germinative neuroepithelial cells. To determine the identity of the neural
      precursors expressing plp/dm- 20, a zeomycin resistance gene fused to the lacZ
      reporter was expressed in transgenic mice under the control of the plp regulatory
      sequences. In the three different lines generated, the pattern of beta
      galactosidase expression was similar and superimposable on the expression pattern
      of endogenous plp/dm-20. Both in vivo and in vitro, the transgene was expressed
      by O4(+) pre-oligodendrocytes, and later by RIP+ differentiated oligodendrocytes,
      but not by neuronal cells, astrocytes, or radial glial cells. After zeomycin
      selection, a dramatic enrichment in O4(+) pre-oligodendrocytes was observed in
      cultures derived from E12.5 transgenic embryos. This enrichment indicates the
      oligodendroglial specification of neural precursors that continuously express
      plp/dm-20. Early plp/dm-20-expressing precursors, however, appear to be a
      separate population from previously described PDGFRalpha oligodendrocyte
      precursors, as shown by the striking differences in their (1) patterns of
      distribution and (2) responsiveness to PDGF. These data suggest that
      oligodendrocytes have a plural origin and that early plp/dm-20 defines one of the
      neural lineages generating oligodendrocytes.

PMID- 9763478
TI  - A role for tectal midline glia in the unilateral containment of retinocollicular
      axons.
AB  - Retinal fibers approach close to the tectal midline but do not encroach on the
      other side. Just before the entry of retinal axons into the superior colliculus
      (SC), a group of radial glia differentiates at the tectal midline; the
      spatiotemporal deployment of these cells points to their involvement in the
      unilateral containment of retinotectal axons. To test for such a barrier function
      of the tectal midline cells, we used two lesion paradigms for disrupting their
      radial processes in the neonatal hamster: (1) a heat lesion was used to destroy
      the superficial layers of the right SC, including the midline region, and (2) a
      horizontally oriented hooked wire was inserted from the lateral edge of the left
      SC toward the midline and was used to undercut the midline cells, leaving intact
      the retinorecipient layers in the right SC. In both cases, the left SC was
      denervated by removing its contralateral retinal input. Animals were killed 12 hr
      to 2 weeks later, after intraocular injections of anterograde tracers to label
      the axons from the remaining eye. Both lesions resulted in degeneration of the
      distal processes of the tectal raphe glia and in an abnormal crossing of the
      tectal midline by retinal axons, leading to an innervation of the opposite
      ("wrong") tectum. The crossover occurred only where glial cell attachments were
      disrupted. These results document that during normal development, the integrity
      of the midline septum is critical in compartmentalizing retinal axons and in
      retaining the laterality of the retinotectal projection.

PMID- 9763479
TI  - Spine loss and other persistent alterations of hippocampal pyramidal cell
      dendrites in a model of early-onset epilepsy.
AB  - To explore the anatomical substrates for network hyperexcitability in adult rats
      that become chronically epileptic after recurrent seizures in infancy, the
      dendritic and axonal arbors of biocytin-filled hippocampal pyramidal cells were
      reconstructed. On postnatal day 10, tetanus toxin was unilaterally injected into
      the hippocampus and produced brief but recurrent seizures for 1 week. Later,
      hippocampal slices taken from these rats exhibited synchronized network bursts in
      area CA3C. Both the apical and basilar dendritic arbors of CA3C pyramidal cells
      were markedly abnormal in these epileptic rats. There was a considerable
      reduction in the density of dendrite spines, although the extent of this loss
      could vary among dendritic segments. Spine density on terminal segments of the
      basilar and apical dendrites was reduced on average by 35 and 20%, respectively.
      In addition, the diameters of these same dendritic segments were markedly
      reduced. Dendritic spine loss has previously been suggested to indicate a partial
      deafferentation of epileptic neurons, but this interpretation is difficult to
      reconcile with the critical role recurrent excitatory synaptic transmission plays
      in the generation of synchronized network burst. In this study, axonal arbors of
      CA3C pyramidal cells exhibited normal branching patterns, branching complexity,
      and varicosity density. This suggests that if deafferentation occurs, synapses
      other than recurrent excitatory ones are lost. The morphological abnormalities
      reported here would be expected to significantly alter electrical signaling
      within dendrites that may contribute importantly to seizures and other behavioral
      sequelae of early-onset epilepsy.

PMID- 9763480
TI  - Autocrine hepatocyte growth factor provides a local mechanism for promoting
      axonal growth.
AB  - In this report, we describe a novel local mechanism necessary for optimal axonal
      growth that involves hepatocyte growth factor (HGF). Sympathetic neurons of the
      superior cervical ganglion coexpress bioactive HGF and its receptor, the Met
      tyrosine kinase, both in vivo and in vitro. Exogenous HGF selectively promotes
      the growth but not survival of cultured sympathetic neurons; the magnitude of
      this growth effect is similar to that observed with exogenous NGF. Conversely,
      HGF antibodies that inhibit endogenous HGF decrease sympathetic neuron growth but
      have no effect on survival. This autocrine HGF is required locally by sympathetic
      axons for optimal growth, as demonstrated using compartmented cultures. Thus,
      autocrine HGF provides a local, intrinsic mechanism for promoting neuronal growth
      without affecting survival, a role that may be essential during developmental
      axogenesis or after neuronal injury.

PMID- 9763481
TI  - Patterns of status epilepticus-induced neuronal injury during development and
      long-term consequences.
AB  - The lithium-pilocarpine model of status epilepticus (SE) was used to study the
      type and distribution of seizure-induced neuronal injury in the rat and its
      consequences during development. Cell death was evaluated in hematoxylin- and
      eosin-stained sections and by electron microscopy. Damage to the CA1 neurons was
      maximal in the 2- and 3-week-old pups and decreased as a function of age. On the
      other hand, damage to the hilar and CA3 neurons was minimal in the 2-week-old rat
      pups but reached an adult-like pattern in the 3-week-old animals, and damage to
      amygdalar neurons increased progressively with age. The 3-week-old animals also
      demonstrated vulnerability of the dentate granule cells. To evaluate neuronal
      apoptosis, we used terminal deoxynucleotidyl transferase-mediated biotinylated
      UTP nick end labeling (TUNEL) stain, confocal fluorescence microscopy of ethidium
      bromide-stained sections, electron microscopy, and DNA electrophoresis. Neurons
      displaying all of those features of apoptotic death in response to SE were seen
      in the CA1 region of the 2-week-old pups and in the hilar border of the dentate
      granule cells of the 3-week-old animals. Some (3/11) of the animals that
      underwent SE at 2 weeks of age and most of the animals that underwent SE at 3 or
      4 weeks of age (8/11 and 6/8, respectively) developed spontaneous seizures later
      in life; the latter showed SE-induced synaptic reorganization as demonstrated by
      Timm methodology. These results provide strong evidence for the vulnerability of
      the immature brain to seizure-induced damage, which bears features of both
      necrotic and apoptotic death and contributes to synaptic reorganization and the
      development of chronic epilepsy.

PMID- 9763482
TI  - Multiple limbic regions mediate the disruption of prepulse inhibition produced in
      rats by the noncompetitive NMDA antagonist dizocilpine.
AB  - Prepulse inhibition (PPI), a phenomenon in which a weak prestimulus decreases the
      startle response to an intense stimulus, provides an operational measure of
      sensorimotor gating (a process by which an organism filters sensory information)
      and is diminished in schizophrenia and schizotypal patients. The psychotomimetic
      phencyclidine and its potent congener dizocilpine are noncompetitive antagonists
      of the NMDA receptor complex, and they disrupt PPI in rodents, mimicking the
      clinically observed PPI deficit. The neuroanatomical substrates mediating the PPI
      disruptive effects of noncompetitive NMDA antagonists are unknown. The present
      study sought to identify brain regions subserving the disruption of PPI produced
      by noncompetitive NMDA antagonists in rats. PPI was measured in startle chambers
      immediately after bilateral infusion of dizocilpine (0, 0.25, 1.25, and 6.25
      microgram/0.5 microliter/side) into one of six brain regions: amygdala, dorsal
      hippocampus, medial prefrontal cortex, nucleus accumbens, ventral hippocampus,
      and dorsomedial thalamus. Dizocilpine significantly decreased PPI after infusion
      into the amygdala or dorsal hippocampus. A trend toward PPI disruption was
      observed with administration into medial prefrontal cortex. In contrast, no
      change in PPI was produced by dizocilpine infusion into nucleus accumbens,
      ventral hippocampus, or dorsomedial thalamus. Startle reactivity was increased by
      dizocilpine infusion into amygdala, dorsal hippocampus, nucleus accumbens, and
      dorsomedial thalamus, but not medial prefrontal cortex. These findings indicate
      that multiple limbic forebrain regions mediate the ability of noncompetitive NMDA
      antagonists to disrupt PPI and that the PPI-disruptive and the startle-increasing
      effects of dizocilpine are mediated by different central sites.

PMID- 9763483
TI  - Directional tuning of single motor units.
AB  - The directional activity of whole muscles has been shown to be broadly and often
      multimodally tuned, raising the question of how this tuning is subserved at the
      level of single motor units (SMUs). Previously defined rules of SMU activation
      would predict that units of the same muscle (or at least of the same
      neuromuscular compartment) are activated homogeneously with activity peaks in the
      same "best" direction(s). In the present study, the best directions of SMUs in
      human biceps (both heads) and deltoid (anterior, medial, and posterior portions)
      were determined by measuring the firing rate and threshold force of units for
      recruitment during isometric force ramps in many different directions. For all
      muscles studied, neighboring motor units could have significantly different best
      directions, suggesting that each muscle receives multiple directional commands.
      Furthermore, 17% of the units sampled clearly had a second-best direction,
      consistent with a convergence of different directional commands onto the same
      motoneuron. The best directions of the units changed gradually with location in
      the muscle. Best directions did not cluster into separate groups, thus, not
      supporting the existence of clearly distinguished neuromuscular compartments.
      Instead, the results reveal a more gradually distributed activation of the biceps
      and deltoid motoneuron pools. A model is proposed in which the central control
      mechanism optimizes the fulfillment of the continuously changing directional
      force requirements of a movement by gradually recruiting and derecruiting those
      units ideally suited for the production of the required force vector at any given
      time.

PMID- 9763484
TI  - Reduced striatal dopamine transporter density in abstinent methamphetamine and
      methcathinone users: evidence from positron emission tomography studies with
      [11C]WIN-35,428.
AB  - Methamphetamine and methcathinone are psychostimulant drugs with high potential
      for abuse. In animals, methamphetamine and related drugs are known to damage
      brain dopamine (DA) neurons, and this damage has recently been shown to be
      detectable in living nonhuman primates by means of positron emission tomography
      (PET) with [11C]WIN-35,428, a DA transporter (DAT) ligand. The present studies
      determined whether living humans with a history of methamphetamine or
      methcathinone abuse showed evidence of lasting decrements in brain DAT density.
      PET studies were performed in 10 control subjects, six abstinent methamphetamine
      users, four abstinent methcathinone users, and three patients with Parkinson's
      disease (PD). On average, subjects had abstained from amphetamine use for
      approximately 3 years. Before PET studies, all subjects underwent urine and blood
      toxicology screens to rule out recent drug use. Compared with controls, abstinent
      methamphetamine and methcathinone users had significant decreases in DAT density
      in the caudate nucleus (-23 and -24%, respectively) and putamen (-25 and -16%,
      respectively). Larger decreases in DAT density were evident in patients with PD
      (47 and 68% in caudate and putamen, respectively). Neither methamphetamine nor
      methcathinone users showed clinical signs of parkinsonism. Persistent reductions
      of DAT density in methamphetamine and methcathinone users are suggestive of loss
      of DAT or loss of DA terminals and raise the possibility that as these
      individuals age, they may be at increased risk for the development of
      parkinsonism or neuropsychiatric conditions in which brain DA neurons have been
      implicated.

PMID- 9763485
TI  - Short-term memory for reaching to visual targets: psychophysical evidence for
      body-centered reference frames.
AB  - Pointing to a remembered visual target involves the transformation of visual
      information into an appropriate motor output, with a passage through short-term
      memory storage. In an attempt to identify the reference frames used to represent
      the target position during the memory period, we measured errors in pointing to
      remembered three-dimensional (3D) targets. Subjects pointed after a fixed delay
      to remembered targets distributed within a 22 mm radius volume. Conditions varied
      in terms of lighting (dim light or total darkness), delay duration (0.5, 5.0, and
      8.0 sec), effector hand (left or right), and workspace location. Pointing errors
      were quantified by 3D constant and variable errors and by a novel measure of
      local distortion in the mapping from target to endpoint positions. The
      orientation of variable errors differed significantly between light and dark
      conditions. Increasing the memory delay in darkness evoked a reorientation of
      variable errors, whereas in the light, the viewer-centered variability changed
      only in magnitude. Local distortion measurements revealed an anisotropic
      contraction of endpoint positions toward an "average" response along an axis that
      points between the eyes and the effector arm. This local contraction was present
      in both lighting conditions. The magnitude of the contraction remained constant
      for the two memory delays in the light but increased significantly for the longer
      delays in darkness. These data argue for the separate storage of distance and
      direction information within short-term memory, in a reference frame tied to the
      eyes and the effector arm.

PMID- 9763486
TI  - Cervical dorsal rhizotomy enhances serotonergic innervation of phrenic
      motoneurons and serotonin-dependent long-term facilitation of respiratory motor
      output in rats.
AB  - We tested the hypothesis that spinal plasticity elicited by chronic bilateral
      cervical dorsal rhizotomy (C3-C5; CDR) has functional implications for
      respiratory motor control. Surgery was performed on rats (CDR or sham-operated)
      26 d before phrenic motoneurons were retrogradely labeled with cholera toxin.
      Rats were killed 2 d later, and their spinal cords were harvested and processed
      to reveal the cholera toxin-labeled phrenic motoneurons and serotonin
      immunoreactive terminals. The number of serotonin-immunoreactive terminals within
      5 micrometer of labeled phrenic motoneuron soma and primary dendrites increased
      2.1-fold after CDR versus sham-operation. Time-dependent phrenic motor responses
      to hypoxia were compared among CDR, sham-operated, and control rats.
      Anesthetized, paralyzed, vagotomized, and artificially ventilated rats were
      exposed to three, 5 min episodes of isocapnic hypoxia (FiO2 = 0.11), separated by
      5 min hyperoxic intervals (FiO2 = 0.5). One hour after hypoxia, a long-lasting,
      serotonin-dependent enhancement of phrenic motor output (long-term facilitation)
      was observed in both sham and control rats. After CDR, long-term facilitation was
      108 and 163% greater than control and sham responses, respectively. Pretreatment
      of CDR rats with a 5-HT2 receptor antagonist (ketanserin tartrate, 2 mg/kg, i.v.)
      before episodic hypoxia prevented long-term facilitation and revealed a modest (
      28 +/- 13%; p < 0.05) long-lasting depression of phrenic motor output. The
      results indicate that CDR: (1) increases serotonergic innervation of the phrenic
      motor nucleus; and (2) augments serotonin-dependent long-term facilitation of
      phrenic motor output. These results further suggest a form of plasticity based on
      changes in the capacity for neuromodulation.

PMID- 9763487
TI  - Amygdalar NMDA receptors are critical for new fear learning in previously fear
      conditioned rats.
AB  - NMDA receptors in the amygdala seem to be critical for fear conditioning in naive
      rats. Recent spatial-learning studies suggest that previous learning protected
      animals from the amnesic effect of NMDA antagonists on new learning (of a similar
      behavioral task). Therefore, the present study examined whether blocking of NMDA
      receptors in the basolateral nucleus of the amygdala (BLA) prevents new fear
      learning in previously fear-conditioned rats, as measured by freezing behavior.
      Intra-BLA infusions of the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric
      acid (APV) completely blocked fear conditioning to a tone stimulus in animals
      that had previously been fear-conditioned to a light stimulus. Similar results
      were obtained with intra-BLA infusions of APV before contextual fear conditioning
      in rats that had been fear-conditioned to a different context. Additional
      experiments showed that intra-BLA APV infusions substantially interfere with the
      expression and extinction of conditioned fear to tone, light, and context
      stimuli. Together, these results indicate that NMDA receptors in the BLA are
      crucial for the encoding of new fear memories (i.e., the formation of specific
      conditioned stimulus-unconditioned stimulus association), the expression of
      conditioned fear responses, and the extinction of acquired fear.

PMID- 9763488
TI  - Spatial firing properties of hippocampal CA1 populations in an environment
      containing two visually identical regions.
AB  - Populations of 10-39 CA1 pyramidal cells were recorded from four rats foraging
      for food reward in an environment consisting of two nearly identical boxes
      connected by a corridor. For each rat, a higher-than-chance fraction of cells had
      similarly shaped spatial firing fields in both boxes, but other cells had
      completely different fields in the two boxes. The level of correlation of fields
      in the two boxes differed greatly across rats and, for three of the four rats,
      across recording sessions. Thus, the factors controlling the level of correlation
      are likely to be subtle. Two control manipulations were performed. First, the two
      boxes were physically interchanged. In no case did firing fields move along with
      the boxes. Second, on the final session of recording, the rat was started in the
      south box, after having been started in the north box for every previous session.
      For at least two of the four rats, the north fields from the previous session
      were instantiated in the south during the first visit of the second session, but
      thereafter reverted. Thus neither differences between the physical boxes nor
      sensory input from outside the apparatus could account for the differences in
      firing fields: most likely they were caused by a combination of learned
      expectations and a neural mechanism for remembering movements. These findings
      could be explained either by hypothesizing a more sophisticated attractor-map
      architecture than has been proposed previously, or by hypothesizing that the
      hippocampus conjunctively encodes both map information and some other type of
      information.

PMID- 9763489
TI  - Prepulse inhibition of the Tritonia escape swim.
AB  - Presenting a weak stimulus just before a strong, startle stimulus reduces the
      amplitude of the ensuing startle response in humans and other vertebrates. This
      phenomenon, termed "prepulse inhibition" (PPI), appears to function to reduce
      distraction while processing sensory input. To date, no detailed neural mechanism
      has been described for PPI. Here we demonstrate PPI in the marine mollusk
      Tritonia diomedea, which has a nervous system highly suitable for cellular
      analyses. We found that a 100 msec vibrotactile prepulse prevented the animal's
      escape swim response to a closely following 1 sec tail shock. This inhibition was
      highly transient, with a significant effect lasting just 2.5 sec. These findings
      indicate that the Tritonia escape swim response undergoes a form of PPI
      phenomenologically similar to that observed in vertebrates. Further tests showed
      that the vibrotactile stimulus had no inhibitory effect if applied after tail
      shock, while the animal was preparing to swim, but it acted to terminate swims
      once they were actively under way. As a first step toward a cellular analysis of
      PPI, we recorded from neurons of the swim circuit in a semi-intact preparation
      and found that the vibrotactile stimulus used in the behavioral experiments also
      prevented the tail shock-elicited swim motor program. These results represent the
      first explicit demonstration of PPI in an invertebrate and establish Tritonia as
      a model system for analyzing its physiological basis.

PMID- 9763490
TI  - Correlative ultrastructural distribution of neurotensin receptor proteins and
      binding sites in the rat substantia nigra.
AB  - Neurotensin (NT) produces various stimulatory effects on dopaminergic neurons of
      the rat substantia nigra. To gain insight into the subcellular substrate for
      these effects, we compared by electron microscopy the distribution of
      immunoreactive high-affinity NT receptor proteins (NTRH) with that of high
      affinity 125I-NT binding sites in this region of rat brain. Quantitative analysis
      showed a predominant association of immunogold and radioautographic labels with
      somata and dendrites of presumptive dopaminergic neurons, and a more modest
      localization in myelinated and unmyelinated axons and astrocytic leaflets. The
      distributions of immunoreactive NTRH and 125I-NT binding sites along
      somatodendritic plasma membranes were highly correlated and homogeneous,
      suggesting that membrane-targeted NTRH proteins were functional and predominantly
      extrasynaptic. Abundant immunocytochemically and radioautographically labeled
      receptors were also detected inside perikarya and dendrites. Within perikarya,
      these were found in comparable proportions over membranes of smooth endoplasmic
      reticulum and Golgi apparatus, suggesting that newly synthesized receptor
      proteins already possess the molecular and conformational properties required for
      effective ligand binding. By contrast, dendrites showed a proportionally higher
      concentration of immunolabeled than radiolabeled intracellular receptors. A
      fraction of these immunoreactive receptors were found in endosomes, suggesting
      that they had undergone ligand-induced internalization and were under a molecular
      conformation and/or in a physical location that precluded their recognition by
      and/or access to exogenous ligand. Our results provide the first evidence that
      electron microscopic immunocytochemistry of the NT receptor identifies sites for
      both the binding and trafficking of NT in the substantia nigra.

PMID- 9763491
TI  - Nicotine selectively enhances NMDA receptor-mediated synaptic transmission during
      postnatal development in sensory neocortex.
AB  - The neurotransmitters acetylcholine (ACh) and glutamate have been separately
      implicated in synaptic plasticity during development of sensory neocortex. Here
      we show that these neurotransmitters can, in fact, act synergistically via their
      actions at nicotinic ACh receptors (nAChRs) and NMDA receptors, respectively. To
      determine how activation of nAChRs modifies glutamatergic EPSPs, we made whole
      cell recordings from visualized pyramidal neurons in slices of rat auditory
      cortex. Pulsed (pressure) ejection of nicotine onto apical dendrites selectively
      enhanced EPSPs mediated by NMDA receptors without affecting AMPA/kainate
      (AMPA/KA) receptor-mediated EPSPs. The enhancement occurred during a transient,
      postnatal period of heightened cholinergic function [neurons tested on postnatal
      day 8-16 (P8-16)], and not in the mature cortex (>P19). Three related findings
      indicated the mechanism of action: (1) The specific alpha7 nAChR antagonist
      methyllycaconitine citrate (MLA) blocked the effect of nicotine; (2) pulsed
      nicotine did not enhance postsynaptic depolarizations induced by
      iontophoretically applied NMDA; and (3) bath exposure to nicotine for several
      minutes produced apparent nAChR desensitization and precluded enhancement of
      EPSPs by pulsed nicotine. Together, the data suggest that nicotine acts at
      rapidly desensitizing, presynaptic alpha7 nAChRs to increase glutamate release
      onto postsynaptic NMDA receptors. The synergistic actions mediated by alpha7
      nAChRs and NMDA receptors may contribute to experience-dependent synaptic
      plasticity in sensory neocortex during early postnatal life.

PMID- 9763492
TI  - The visuo-motor pathway in the local circuit of the rat superior colliculus.
AB  - Intrinsic circuit of the superior colliculus (SC), in particular the pathway from
      the optic tract (OT) to neurons in the intermediate layer (SGI), was investigated
      by whole-cell patch-clamp recording in slice preparations obtained from 17- to 24
      d-old rats. Stimulation of the OT induced monosynaptic EPSPs in neurons in the
      superficial gray layer (SGS) and the optic layer (SO), and disynaptic or
      polysynaptic EPSPs in a majority of SGI neurons. Stimulation of the SGS induced
      monosynaptic or oligosynaptic EPSPs in the SGI neurons. Both the monosynaptic
      EPSPs induced in the SGS/SO neurons by stimulation of the OT and those induced in
      the SGI neurons by stimulation of the SGS were mediated by AMPA- and NMDA-type
      glutamate receptors. Thus, we have clarified the existence of the glutamatergic
      excitatory pathway from the OT to the SGI neurons via SGS and SO neurons. The
      EPSPs in the SGI neurons induced by stimulation of the OT or SGS were remarkably
      enhanced by bicuculline, suggesting that the signal transmission in this pathway
      is under strong suppression by the GABAergic system.

PMID- 9763493
TI  - Mice lacking the beta3 subunit of the GABAA receptor have the epilepsy phenotype
      and many of the behavioral characteristics of Angelman syndrome.
AB  - Angelman syndrome (AS) is a severe neurodevelopmental disorder resulting from a
      deletion/mutation in maternal chromosome 15q11-13. The genes in 15q11-13
      contributing to the full array of the clinical phenotype are not fully
      identified. This study examines whether a loss or reduction in the GABAA receptor
      beta3 subunit (GABRB3) gene, contained within the AS deletion region, may
      contribute to the overall severity of AS. Disrupting the gabrb3 gene in mice
      produces electroencephalographic abnormalities, seizures, and behavior that
      parallel those seen in AS. The seizures that are observed in these mice showed a
      pharmacological response profile to antiepileptic medications similar to that
      observed in AS. Additionally, these mice exhibited learning and memory deficits,
      poor motor skills on a repetitive task, hyperactivity, and a disturbed rest
      activity cycle, features all common to AS. The loss of the single gene, gabrb3,
      in these mice is sufficient to cause phenotypic traits that have marked
      similarities to the clinical features of AS, indicating that impaired expression
      of the GABRB3 gene in humans probably contributes to the overall phenotype of
      Angelman syndrome. At least one other gene, the E6-associated protein ubiquitin
      protein ligase (UBE3A) gene, has been implicated in AS, so the relative
      contribution of the GABRB3 gene alone or in combination with other genes remains
      to be established.

PMID- 9763494
TI  - Medial forebrain bundle lesions fail to structurally and functionally disconnect
      the ventral tegmental area from many ipsilateral forebrain nuclei: implications
      for the neural substrate of brain stimulation reward.
AB  - Lesions in the medial forebrain bundle rostral to a stimulating electrode have
      variable effects on the rewarding efficacy of self-stimulation. We attempted to
      account for this variability by measuring the anatomical and functional effects
      of electrolytic lesions at the level of the lateral hypothalamus (LH) and by
      correlating these effects to postlesion changes in threshold pulse frequency
      (pps) for self-stimulation in the ventral tegmental area (VTA). We implanted True
      Blue in the VTA and compared cell labeling patterns in forebrain regions of
      intact and lesioned animals. We also compared stimulation-induced regional
      [14C]deoxyglucose (DG) accumulation patterns in the forebrains of intact and
      lesioned animals. As expected, postlesion threshold shifts varied: threshold pps
      remained the same or decreased in eight animals, increased by small but
      significant amounts in three rats, and increased substantially in six subjects.
      Unexpectedly, LH lesions did not anatomically or functionally disconnect all
      forebrain nuclei from the VTA. Most septal and preoptic regions contained
      equivalent levels of True Blue label in intact and lesioned animals. In both
      intact and lesioned groups, VTA stimulation increased metabolic activity in the
      fundus of the striatum (FS), the nucleus of the diagonal band, and the medial
      preoptic area. On the other hand, True Blue labeling demonstrated anatomical
      disconnection of the accumbens, FS, substantia innominata/magnocellular preoptic
      nucleus (SI/MA), and bed nucleus of the stria terminalis. [14C]DG autoradiography
      indicated functional disconnection of the lateral preoptic area and SI/MA.
      Correlations between patterns of True Blue labeling or [14C]deoxyglucose
      accumulation and postlesion shifts in threshold pulse frequency were weak and
      generally negative. These direct measures of connectivity concord with the
      behavioral measures in suggesting a diffuse net-like connection between forebrain
      nuclei and the VTA.

PMID- 9763495
TI  - Decreased odor avoidance after electric shock in Drosophila mutants biases
      learning and memory tests.
AB  - The Drosophila mutants amnesiac, dunce (dnc), and rutabaga were isolated after
      associative conditioning tests, during which animals were trained to associate
      the presence of an odor with that of electric shocks (ES). In the absence of
      conditioning, the odor avoidance (OA) of these mutants was shown to be normal,
      indicating that their poor associative conditioning performance was attributable
      to specific learning or memory deficits. However, I show that the OA of the
      mutants is greatly decreased after their exposure to ES. This effect can last for
      hours. These results strongly suggest that part of the defect displayed by these
      mutants in associative conditioning tests does not correspond to a learning or
      memory deficit but might arise from abnormal sensitivity to stressful stimuli. I
      looked at the OA after ES of two previously characterized dnc mutants. Df(1)N79f
      specifically decreases Dnc expression in the mushroom bodies, leading to a normal
      level of learning but decreased memory. Df(1)N79f mutants displayed a normal OA
      after ES. Df(1)N64j15 affects the entire brain expression of Dnc, leading to
      decreased learning and memory. Df(1)N64j15 animals showed a strong decrease of
      their OA after ES. Thus, the lack of Dnc "general" expression is most likely
      responsible for the OA defect, which would be responsible for the apparent
      learning defect after conditioning. In contrast, the Dnc phosphodiesterase
      accumulated in the mushroom bodies would be involved specifically in memory
      formation.

PMID- 9763497
TI  - Editorial 
AB  - We are pleased that the International Journal of Infectious Diseases (IJID) has
      been indexed in MEDLINE and Index Medicus. It is a tribute to those of you who
      have submitted excellent papers, case reports, and reviews and to those who have
      contributed thoughtful editorials. We expect that heightened exposure both online
      and in libraries will result in increased submissions and that this will soon
      warrant publication at bimonthly and eventually monthly intervals. Increased
      frequency of publication depends on members of the International Society for
      Infectious Diseases (ISID) and other colleagues and their submission of more
      manuscripts of the highest scientific merit. We also welcome more letters and
      encourage critical and spirited commentaries. We urge you to tell your libraries
      about the IJID and to suggest that they subscribe. Likewise, colleagues who could
      not attend our biannual meeting should be asked to subscribe as well as to submit
      the results of their observations and investigations. Much of the credit for the
      success of IJID goes to its editors and reviewers. The peer review process works
      because of the expertise, diligence, and timeliness of the reviewers and the
      experience and judgment of the editors. The editors select reviewers, consider
      their comments, and determine how to respond to potential contributors. The
      overall objective is to present information about infectious diseases that has
      international significance. Since these data frequently originate from regions
      where English is not the primary language, our staff will provide assistance in
      editing manuscripts to improve grammar and usage. Command of the English language
      is not a criterion for acceptance or rejection of a manuscript. However, it does
      make it easier for the reviewers if a native English speaker has read and revised
      the manuscript. The recent meeting of the ISID in Boston was clearly a huge
      success, and the presentations were outstanding. We trust that many of you who
      participated in this meeting will submit articles to the IJID. Suggestions for
      supplements from this meeting or from other meetings also are welcomed. Our
      second issue comprised the proceedings at the Jenner Symposium of the 7th
      International Congress for Infectious Diseases in Hong Kong, June 10-13, 1996. An
      independent supplement on fungal infections came from a symposium at the meeting
      of the International Immunocompromised Host Society, June 23-26, 1996, Assisi,
      Italy.

PMID- 9763496
TI  - Synaptic regulation of action potential timing in neostriatal cholinergic
      interneurons.
AB  - Action potentials in neostriatal cholinergic interneurons recorded in vivo are
      triggered by summation of two or three discrete synaptic depolarizations (Wilson
      et al., 1990). The ability and precision with which EPSPs and IPSPs regulate
      action potential timing was therefore investigated in vitro. Cholinergic
      interneurons were identified on the basis of morphological and
      electrophysiological characteristics in neostriatal slices taken from 2- to 3
      week-old postnatal rats recorded at 24-26 degreesC. During periods of induced
      regular firing, intrastriatal stimuli were used to evoke pharmacologically
      isolated monosynaptic AMPA receptor-mediated EPSPs or GABAA receptor-mediated
      IPSPs. EPSPs evoked during the interspike interval (ISI) produced a phase
      dependent decrease in the ISI, whereas IPSPs produced a phase-independent
      prolongation of the ISI. Injection of brief depolarizing currents mimicked the
      action of EPSPs and revealed an alteration in the input resistance during the
      ISI. In contrast to IPSPs, the ability of brief hyperpolarizing current
      injections to delay spike generation was phase-dependent. After blockade of
      GABAergic and glutamatergic synaptic transmission, stimuli failed to produce a
      detectable conductance change but could still prolong the subsequent ISI
      primarily through a D1 dopamine receptor-mediated enhancement of the
      afterhyperpolarization (AHP). Hence, EPSPs are ideally suited to provide a
      precise regulation of spike timing in cholinergic cells, whereas IPSPs are more
      likely to influence the overall level of excitability. The D1-mediated modulation
      of the AHP may contribute to the prolonged ISI seen in tonically active neurons
      in vivo in monkeys trained to respond to a sensory cue.

PMID- 9763498
TI  - Host factors that affect sexual transmission of HIV.

PMID- 9763499
TI  - CD3+CD8+ cell levels as predictors of transmission in human immunodeficiency
      virus-infected couples: a report from the heterosexual HIV transmission study.
AB  - OBJECTIVE: The goal of this study was to identify in human immunodeficiency virus
      (HIV)-infected individuals immunologic markers that correlated with transmission
      of HIV by heterosexual contact. METHODS: In a case-control comparison of couples,
      immunologic and viral parameters were evaluated in 343 HIV-positive individuals
      who were members of 67 HIV-seroconcordant couples (both partners HIV positive)
      and 211 HIV serodiscordant couples (one positive, one negative). RESULTS: The
      most striking immunologic finding was the increased numbers of CD3+CD8+ cells
      found in the index member of discordant couples as compared to the index member
      of the concordant couples. Differences in CD3+CD8+ levels persisted after
      adjustment for stage of disease and CD3+CD4+ count. This increase in the number
      of CD3+CD8+ cells was accompanied by a concomitant decrease in the amount of
      viral replication measured by both HIV culture endpoint and quantitative RNA
      polymerase chain reaction (PCR). CONCLUSION: Data presented here further support
      the role of CD3+CD8+ cells in suppressing or controlling viral activity, although
      a causal role based on case-control data must be advanced cautiously. This in
      vivo biologic function may help prevent or lower the risk of HIV transmission.

PMID- 9763500
TI  - Immunogenicity and reactogenicity of a combined hepatitis A-hepatitis B vaccine
      in adolescents.
AB  - OBJECTIVE: To evaluate the immunogenicity and reactogenicity of two lots of a
      combined hepatitis A-hepatitis B vaccine (HAV, HBV) in healthy 15 to 18 year
      olds. DESIGN: This was a double-blind, randomized clinical study. Vaccine was
      administered into the deltoid at 0, 1, and 6 months. Immunogenicity was assessed
      by anti-HAV and anti-HBs antibody levels at 2, 6, and 7 months after the first
      vaccine dose. Reactogenicity was assessed through use of 3-day diary cards
      following each vaccination, plus recording other unsolicited reactions. RESULTS:
      A total of 160 adolescents were vaccinated; 155 who were seronegative for
      hepatitis A and B at baseline and who completed the study were included in the
      immunogenicity analysis. The vaccine was well tolerated; most side effects were
      local, of low intensity and short duration. Good immunogenicity was determined by
      antibody titers. High rates of seropositivity (99.4%) were achieved after two
      doses against HAV, and after three doses for anti-HBs (seroprotection = 98.7%).
      CONCLUSIONS: This combination vaccine will be useful for immunizing selected high
      risk groups in developed countries. In countries where endemicity is low for both
      diseases, targeting students prior to risk of acquisition would be a feasible
      preventive strategy.

PMID- 9763502
TI  - Screening for human immunodeficiency virus type 1 and 2 in a Turkish blood donor
      population.
AB  - OBJECTIVES: To determine the prevalence of human immunodeficiency virus-1 and -2
      infection in voluntary blood donors at a university hospital in the third largest
      city of Turkey and to evaluate the HIV testing strategy for notifying blood
      donors. METHODS: Between July 1995 and August 1997, 36,373 voluntary blood donors
      who met the criteria for donating blood were tested for the presence of HIV-1 and
      -2 antibodies by using an automated enzyme-linked fluorescent immunoassay.
      Repeatedly reactive samples were subjected to a different enzyme-linked
      immunosorbent assay (ELISA) and a line immunoassay (LIA) for the detection of
      antibodies. RESULTS: Of the 36,373 samples tested 72 were found to be repeatedly
      reactive or borderline by the first screening enzyme immunoassay (EIA). None of
      the 72 samples was reactive by the second EIA. These samples were further tested
      by LIA: 64 were negative on the line immunoassay and 8 were indeterminate. Three
      of eight donors who had indeterminate results by LIA were tested for HIV-1 DNA by
      polymerase chain reaction (PCR) and were found to be negative. One additional
      donor with an indeterminate LIA was found to be negative by EIA and LIA during
      the 6-month follow-up period. CONCLUSION: Donor questioning, repeat EIA testing,
      LIA testing, and HIV-1 DNA analysis did not confirm evidence for HIV infection
      among this blood donor population. Blood donor notification of test results
      according to the World Health Organization (WHO) strategy III was found to be an
      appropriate approach.

PMID- 9763501
TI  - Expansion of epidemic dengue viral infections to Pakistan.
AB  - OBJECTIVES: Antibodies to dengue viruses have occasionally been reported in
      individuals in Pakistan, but the frequency of occurrence of dengue infection in
      Pakistan is unclear. The first confirmed dengue hemorrhagic fever outbreak in
      Pakistan occurred in 1994. In October 1995, the authors investigated an outbreak
      of a febrile illness among employees of a construction contractor at a power
      generation plant in Baluchistan, Pakistan, to determine the cause of illness and
      recommend appropriate preventive measures. METHODS: The work site and living
      arrangements were inspected, a questionnaire was administered, and serum samples
      were collected from all consenting contractor employees and their families if
      they lived at the camp. Sera were analyzed for IgM against dengue virus, using an
      enzyme-linked immunosorbent assay. RESULTS: Interviews were conducted with 76
      persons (mean age, 42y); 95% were men. Forty-two persons (55%) reported having
      experienced fever, headache, or myalgia in the preceding 6 weeks. Fifty-seven
      subjects (75%) had IgM antibodies against at least one dengue serotype; 45
      subjects (59%) had IgM antibodies against dengue serotype 2. CONCLUSION: This was
      an outbreak of dengue fever due to multiple serotypes of dengue virus. This
      confirms that epidemic dengue infection was present in southern Pakistan for 2
      consecutive years.

PMID- 9763504
TI  - Pseudomonas aeruginosa bacteremia: an analysis of 123 episodes, with particular
      emphasis on the effect of antibiotic therapy.
AB  - OBJECTIVES: To review current experience with Pseudomonas aeruginosa bacteremia
      and compare outcome of patients treated with single-drug, versus combination
      therapy. METHODS: The charts of all patients with P. aeruginosa bacteremia
      between 1990 and 1992 were reviewed, and pertinent demographic, clinical, and
      bacteriologic data were retrieved. In addition, similar data were collected from
      a series of patients with P. aeruginosa bacteremia from the literature of the
      past 20 years. RESULTS: One hundred and twenty-three episodes of P. aeruginosa
      bacteremia in 121 patients were identified. Most patients were older than 70
      years, had at least one underlying condition, and had acquired the infection in
      the hospital. Attributable mortality was 34%. After exclusion for early mortality
      and inappropriate therapy, 57 patients remained eligible for comparison of
      outcome according to therapy protocol. Mortality from infection was equal between
      the group of 42 patients who received monotherapy and the 15 patients who
      received combination therapy (14% and 13%, respectively). The literature review
      revealed eight articles describing 21 to 410 episodes of Pseudomonas bacteremia.
      The clinical characteristics of these series did not differ significantly from
      those of the present series. CONCLUSIONS: Incidence, epidemiology, clinical
      characteristics, and outcome of pseudomonas sepsis did not change significantly
      over the past 2 decades. Appropriate monotherapy was as effective as combination
      drug therapy for individuals with pseudomonas bacteremia surviving the first 2
      days of infection.

PMID- 9763503
TI  - Varicella infection and pneumonia among adults.
AB  - OBJECTIVES: To demonstrate the clinical importance of adult chickenpox in terms
      of morbidity, mortality, and impact on hospital services, in Al Ain, United Arab
      Emirates. METHODS: A review was conducted of 607 consecutive hospitalized cases
      of adult chickenpox (1985-1996, Al Ain Hospital) for clinical findings and risk
      of developing varicella pneumonia. RESULTS: Leading clinical features were fever
      (98.9%), myalgia (26.9%), cough (24.6%), headache (15.4%), pharyngitis (14.7%),
      and profuse rash (12.2%). There were 26 cases of varicella pneumonia, of whom
      three died with respiratory failure (hospital case fatality 0.5%). Multivariate
      analysis (odds ratios in parenthesis) showed that cough (12.1), profuse rash
      (4.5), fever for more than 1 week (3.9), and age over 34 years (2.3) were the
      most significant predictors of pneumonia. CONCLUSIONS: Early aggressive therapy
      with intravenous acyclovir is recommended in patients at risk of pneumonia. In
      the community setting, there is a large proportion of adult immigrants
      (especially from South Asia) who are seronegative and at risk of complications
      and hospitalization. It is recommended that the varicella vaccine be offered to
      new immigrants after screening, to benefit themselves and the nonexposed
      community, and to reduce the economic burden of chickenpox on the health services
      and employers.

PMID- 9763505
TI  - Molecular analysis of the a determinant of HBsAg in children of HBeAg-positive
      mothers upon failure of postexposure prophylaxis.
AB  - OBJECTIVE: To investigate the a determinant of hepatitis B virus (HBV) S gene for
      the presence of mutations responsible for vaccine failure. METHODS: The a
      determinant of HBV S gene was amplified in sera obtained from 11 HBV-positive
      infants and children born to asymptomatic HBeAg-positive mothers by nested
      polymerase chain reaction (PCR) and subsequently subjected to direct sequencing.
      The sequences obtained were translated into the corresponding amino acids and
      compared to amino acid sequences of HBV subtype adr. All infants under
      investigation had received recombinant hepatitis B vaccine within 24 hours after
      delivery and had completed the recommended vaccination course, consisting of
      three to four doses administered at defined intervals. RESULTS: The usual
      divergence regarding genotype and subtype was identified among the 11 samples
      tested. Only two exhibited a point mutation within the a determinant, one of
      which consisted of a substitution of glycine with alanine at position 145, and
      the other of a substitution of glutamine with arginine at position 129.
      CONCLUSION: Eleven neonates were positive for HBV infection, and two of them
      showed point mutations that might have rendered the virus resistant to the
      vaccine, possibly due to a change in the S protein's secondary structure. Yet,
      this remains a matter of speculation, since the other seven cases positive for
      hepatitis B viral DNA merely demonstrated the usual genotype and subtype. The
      presence of escape mutants of HBV can be considered rather negligible with
      respect to vaccination programs, especially as the vaccine has been shown to
      reduce hepatitis B, as well as hepatocellular carcinoma efficiently.

PMID- 9763506
TI  - Evaluation of the serologic response against two consensus V3 loop peptides from
      human immunodeficiency virus-1 in Cuban patients.
AB  - OBJECTIVES: A retrospective study was conducted to evaluate the antibody response
      of Cuban patients infected with human immunodeficiency virus (HIV)-1 against two
      consensus peptides from the third variable domain (V3) loop of glycoprotein
      gp120. METHODS: The study included sera from 10 individuals at different stages
      of disease. Two 15-meric synthetic peptides designed from a consensus sequence,
      belonging to group B or C of HIV-1, were used to determine antibody titers and
      avidity indexes in an indirect enzyme-linked immunoassay. RESULTS: A high
      reactivity against both peptides was detected, with 80% of the sera reacting with
      at least one of the peptides. The antibody titers and avidity indexes did not
      correlate with disease progression. Additionally, for one of the patients from
      whom the virus had been isolated, a higher avidity index was found against the
      homologous peptide. CONCLUSIONS: This study showed high reactivity against two
      consensus peptides from the V3 loop of gp120 among patients with HIV. Large scale
      studies are needed to determine whether the titers or avidity of anti-V3
      antibodies, at the early stages of infection, are predictive of disease
      progression. Both peptides are candidates for inclusion in experimental vaccines.

PMID- 9763507
TI  - Catheter-related infection: an update on diagnosis, treatment, and prevention.
AB  - Catheter-related infection (CRI) accounts for a large percentage of nosocomial
      infections, and related bacteremia is a common complication. Bacteremia arises in
      approximately 1 of 15 episodes of CRI and causes considerable morbidity and
      occasional mortality, as well as increased medical costs. The diagnosis of CRI
      and catheter-related bacteremia (CRB) is still a challenge for practitioners
      treating catheterized patients. Semiquantitative tip culture by the roll-plate
      method is the cornerstone for diagnosis of CRI in routine practice. However,
      there is a great deal of interest in the alternative methods for diagnosing CRI
      without catheter withdrawal, since treatment of the patient can be successfully
      completed with the infected device maintained in place. The conservative
      management of CRI includes perfusion of antibiotics through the infected catheter
      and the antibiotic-lock technique (ALT). Catheter-related infection prevention is
      accomplished mainly by strict adherence to hygienic practices in insertion and
      manipulation of the catheter. However, knowledge of the pathophysiology of CRI
      has led to the development of new sophisticated catheters and hubs that
      incorporate mechanical and antibacterial barriers.

PMID- 9763509
TI  - ELAV protein HuA (HuR) can redistribute between nucleus and cytoplasm and is
      upregulated during serum stimulation and T cell activation.
AB  - ELAV proteins are implicated in regulating the stability and translation of
      cytokine and growth regulatory mRNAs such as GM-CSF, IL-2, c-myc, c-fos and GLUT1
      by binding to their AU-rich 3'UTRs. The tissue-specific ELAV protein HuB (aka.
      Hel-N1) is predominantly cytoplasmic and has been shown to stabilize GLUT1 and c
      myc mRNAs and to increase their translation following ectopic expression in 3T3
      L1 cells. We report that the most widely expressed mouse ELAV protein, mHuA, is
      predominately nuclear in cultured NIH-3T3 cells, but is localized in the
      cytoplasm during early G1 of the cell cycle. Therefore, much like the primarily
      cytoplasmic HuB, HuA becomes temporally localized in the cytoplasm where it can
      potentially regulate the stability or translation of bound mRNAs. Moreover, we
      report that stimulation of mouse spleen cells using either mitogenic or sub
      mitogenic levels of anti-CD3/CD28 resulted in a dramatic increase in the level of
      HuA. Upregulation of HuA corresponds to previously documented increases in
      cytokine expression which are due to increased mRNA stability following T cell
      activation. Consistent with these findings, HuA was down regulated in quiescent
      cells and upregulated in 3T3 cells following serum stimulation. The increase of
      murine HuA during the cell cycle closely resembles that of cyclin B1 which peaks
      in G2/M. Together with our earlier studies, these data indicate that mammalian
      ELAV proteins function during cell growth and differentiation due in part to
      their effects on posttranscriptional stability and translation of multiple growth
      regulatory mRNAs. This supports the hypothesis that ELAV proteins can function as
      transacting factors which affect a default pathway of mRNA degradation involved
      in the expression of growth regulatory proteins.

PMID- 9763508
TI  - A factor required for nonsense-mediated mRNA decay in yeast is exported from the
      nucleus to the cytoplasm by a nuclear export signal sequence.
AB  - In Saccharomyces cerevisiae, Upf3p is required for nonsense-mediated mRNA decay
      (NMD). Although localized primarily in the cytoplasm, Upf3p contains three
      sequence elements that resemble nuclear localization signals (NLSs) and two
      sequence elements that resemble nuclear export signals (NESs). We found that a
      cytoplasmic reporter protein localized to the nucleus when fused to any one of
      the three NLS-like sequences of Upf3p. A nuclear reporter protein localized to
      the cytoplasm when fused to one of the NES-like sequences (NES-A). We present
      evidence that NES-A functions to signal the export of Upf3p from the nucleus.
      Combined alanine substitutions in the NES-A element caused a re-distribution of
      Upf3p to a subnuclear location identified as the nucleolus and conferred an Nmd-
      phenotype. Single mutations in NES-A failed to affect the distribution of Upf3p
      and were Nmd+. When an NES element from HIV-1 Rev was inserted near the C
      terminus of a mutant Upf3p containing multiple mutations in NES-A, the
      cytoplasmic distribution typical of wild-type Upf3p was restored but the cells
      remained phenotypically Nmd-. These results suggest that NES-A is a functional
      nuclear export signal. Combined mutations in NES-A may cause multiple defects in
      protein function leading to an Nmd- phenotype even when export is restored.

PMID- 9763510
TI  - Protein synthesizing units in presynaptic and postsynaptic domains of squid
      neurons.
AB  - Putative protein synthesizing domains, called plaques, are characterized in the
      squid giant synapse and axon and in terminals of squid photoreceptor neurons.
      Plaques are oval-shaped formations of about 1 microm in size, which (1) generate
      signals that have spectroscopic electron energy loss characteristics of
      ribosomes, (2) exhibit ribonuclease-sensitive binding of YOYO-1, a fluorescent
      RNA/DNA dye, and (3) in part hybridize with a poly(dT) oligonucleotide. In the
      giant synapse plaques are abundant in the postsynaptic area, but are absent in
      the presynaptic terminal. In the cortical layer of the optic lobes, plaques are
      localized in the large carrot-shaped presynaptic terminals of photoreceptor
      neurons, where they are surrounded by synaptic vesicles and mitochondria.
      Biochemical and autoradiographic data have documented that the protein synthetic
      activity of squid optic lobe synaptosomes is largely due to the presynaptic
      terminals of the photoreceptor neurons. The identification of ribosomes and
      poly(A+)-mRNA in the plaques indicates that these structures are sites of local
      protein synthesis in synaptic domains.

PMID- 9763511
TI  - Tau interacts with src-family non-receptor tyrosine kinases.
AB  - Tau and other microtubule-associated proteins promote the assembly and
      stabilization of neuronal microtubules. While each microtubule-associated protein
      has distinct properties, their in vivo roles remain largely unknown. Tau is
      important in neurite outgrowth and axonal development. Recently, we showed that
      the amino-terminal region of tau, which is not involved in microtubule
      interactions, is important in NGF induced neurite outgrowth in PC12 cells. Here
      we report that a proline rich sequence in the amino terminus of tau interacts
      with the SH3 domains of fyn and src non-receptor tyrosine kinases. Tau and fyn
      were co-immunoprecipitated from human neuroblastoma cells and co-localization of
      tau and fyn was visualized in co-transfected NIH3T3 cells. Co-transfection of tau
      and fyn also resulted in an alteration in NIH3T3 cell morphology, consistent with
      an in vivo interaction. Fyn-dependent tyrosine phosphorylation of tau occurred in
      transfected cells and tyrosine phosphorylated tau was identified in human
      neuroblastoma cells as well. Our data suggest that tau is involved in signal
      transduction pathways. An interaction between tau and fyn may serve as a
      mechanism by which extracellular signals influence the spatial distribution of
      microtubules. The tyrosine phosphorylation of tau by fyn may also have a role in
      neuropathogenesis, as fyn is upregulated in Alzheimer's disease.

PMID- 9763512
TI  - The C8/144B monoclonal antibody recognizes cytokeratin 15 and defines the
      location of human hair follicle stem cells.
AB  - Stem cells are vital for the homeostasis of self-renewing tissues such as the
      hair follicle. Epithelial stem cells have been implicated in tumorigenesis and
      wound healing, and their manipulation may have wide ranging applications
      including gene therapy and tissue transplantation. Rodent hair follicle stem
      cells have been localized to an area of the follicle called the bulge, however,
      the identification and characterization of human hair follicle stem cells has
      been hampered by a lack of cellular markers for this area. We have determined
      that the C8/144B monoclonal antibody, originally generated against a short
      intracytoplasmic peptide of CD8, preferentially immunostains hair follicle bulge
      keratinocytes without staining the remaining hair follicle. Using expression
      cloning, we identified cytokeratin 15 as the keratinocyte protein recognized by
      the C8/144B monoclonal antibody. By delineating the bulge using this antibody, we
      demonstrated that bulge cells possess a stem cell phenotype characterized by
      their slowly-cycling nature, preferential proliferation at the onset of new hair
      follicle growth, high level of beta1 integrin expression, and expression of
      cytokeratin 19.

PMID- 9763513
TI  - Tension-sensitive kinetochore phosphorylation in vitro.
AB  - Many cells have a checkpoint that detects a single misattached chromosome and
      delays anaphase, allowing time for error correction. Detection probably depends
      on tension-sensitive kinetochore protein phosphorylation. Somehow, mechanical
      tension, or some consequence of tension, produces a chemical change,
      dephosphorylation. The mechanism of tension-mediated dephosphorylation can be
      approached using an in vitro system. Earlier work showed that the kinetochores of
      washed chromosomes from a mammalian cell line can be phosphorylated in vitro
      simply by incubation with ATP and a phosphatase inhibitor. We confirm this for
      chromosomes from insect meiotic cells. Thus, kinetochores of washed chromosomes
      from diverse sources contain a complete phosphorylation system: a kinase, a
      phosphatase and the substrate protein(s). We show that phosphorylation in vitro
      is sensitive to tension, as it is in living cells. This makes the conditions
      required for phosphorylation in vitro relevant to the process in living cells.
      The phosphatase is ruled out as the tension-sensitive component in vitro, leaving
      either the kinase or the substrate as the sensitive component. We show that a
      kinase extracted from mammalian cells in mitosis phosphorylates the kinetochores
      of insect meiotic chromosomes very effectively. The mammalian kinase under
      phosphorylates the kinetochore of the insect's X-chromosome, just as the native
      insect kinase does. This provides a clue to the evolution of a chromosome that is
      not detected by the checkpoint. The mammalian kinase is not tightly bound to the
      chromosome and thus functions primarily in solution. This suggests that the
      substrate's phosphorylatable groups are freely available to outside constituents,
      e.g. regulators, as well as to the kinetochore's own kinase and phosphatase.

PMID- 9763514
TI  - Cytoplasmic calcium gradients and calmodulin in the early development of the
      fucoid alga Pelvetia compressa.
AB  - The predicted existence of cytoplasmic Ca2+ gradients during the
      photopolarization of the zygotes of the brown algae, Pelvetia and Fucus, has
      proved to be difficult to establish, and the downstream targets of the putative
      gradients are not known. We have used quantitative microinjection of the long
      excitation wavelength Ca2+ indicator, Calcium Crimson, and of antibodies against
      calmodulin to investigate these matters in the zygotes and early embryos of
      Pelvetia. We found that there is a window of cytoplasmic Calcium Crimson
      concentration that gives an adequate signal above autofluorescence yet allows
      normal development of the zygotes. As Calcium Crimson is not a ratiometric
      indicator, we injected other zygotes with a Ca2+-insensitive dye, rhodamine B,
      and imaged the cells at the same time that Calcium Crimson-injected cells were
      imaged. Ratios were calculated by dividing the averaged pixel values of Calcium
      Crimson images by the averaged pixel values of corresponding rhodamine B images.
      By this method, we observed the formation of a cytoplasmic Ca2+ gradient within
      one hour of the exposure of the cells to unilateral blue light during the
      photosensitive period. The region of high Ca2+ was localized to and predictive of
      the site of future rhizoid formation. We validated this somewhat indirect method
      by applying it to the growing rhizoid, where the existence of a tip-localized
      Ca2+ gradient is well established. The method clearly revealed the known
      gradient. The injection of ungerminated zygotes with antibodies made against
      Dictyostelium calmodulin inhibited germination, and this inhibition was abolished
      if the calmodulin antibodies were coinjected with an excess of purified maize
      calmodulin. Likewise, the growth of the rhizoids was inhibited by calmodulin
      antibody injections. The fungus-derived calmodulin antagonist, ophiobolin A,
      which has previously been shown to be a potent inhibitor of germination, also
      inhibited rhizoidal growth. Our results provide evidence that a cytoplasmic Ca2+
      gradient is present during photopolarization and that calmodulin acts as a
      mediator of Ca2+ gradients throughout the early developmental processes of
      germination and rhizoidal growth in Pelvetia compressa.

PMID- 9763515
TI  - H2O2 acts on cellular membranes to generate ceramide signaling and initiate
      apoptosis in tracheobronchial epithelial cells.
AB  - Hydrogen peroxide (H2O2) is an inflammatory oxidant which contributes to the
      pathogenesis of chronic diseases such as lung injury of the respiratory tract,
      atherosclerosis and cancer. The mechanisms and target sites of this reactive
      oxidant are mainly unknown. So far there are opposing reports as to whether
      reactive oxidants inhibit or promote apoptosis. We activated the death pathway in
      primary tracheobronchial epithelial (TBE) cells with H2O2 (20-200 microM) and
      observed the morphological changes, DNA laddering patterns, and DNA fragmentation
      associated with apoptosis. Elevation of ceramide with exogenous ceramide analogs
      was sufficient for apoptosis induction with the same characteristics and in the
      same time frame. H2O2 induced rapid sphingomyelin hydrolysis to ceramide, the
      elevation of which paralleled the induction of apoptosis. Furthermore, H2O2 acted
      directly on TBE cells membrane preparations devoid of nuclei, stimulating
      sphingomyelin hydrolysis through a neutral Mg2+ dependent sphingomyelinase
      (SMase). These data suggest that the formation of ceramide from sphingomyelin in
      the plasma membrane is a key event in H2O2-induced apoptosis in tracheobronchial
      epithelial cells.

PMID- 9763516
TI  - Transport of ER vesicles on actin filaments in neurons by myosin V.
AB  - Axoplasmic organelles in the giant axon of the squid have been shown to move on
      both actin filaments and microtubules and to switch between actin filaments and
      microtubules during fast axonal transport. The objectives of this investigation
      were to identify the specific classes of axoplasmic organelles that move on actin
      filaments and the myosin motors involved. We developed a procedure to isolate
      endoplasmic reticulum (ER) from extruded axoplasm and to reconstitute its
      movement in vitro. The isolated ER vesicles moved on exogenous actin filaments
      adsorbed to coverslips in an ATP-dependent manner without the addition of soluble
      factors. Therefore myosin was tightly bound and not extracted during isolation.
      These vesicles were identified as smooth ER by use of an antibody to an ER
      resident protein, ERcalcistorin/protein disulfide isomerase (EcaSt/PDI).
      Furthermore, an antibody to squid myosin V was used in immunogold EM studies to
      show that myosin V localized to these vesicles. The antibody was generated to a
      squid brain myosin (p196) that was classified as myosin V based on comparisons of
      amino acid sequences of tryptic peptides of this myosin with those of other known
      members of the myosin V family. Dual labeling with the squid myosin V antibody
      and a kinesin heavy chain antibody showed that the two motors colocalized on the
      same vesicles. Finally, antibody inhibition experiments were performed with two
      myosin V-specific antibodies to show that myosin V motor activity is required for
      transport of vesicles on actin filaments in axoplasm. One antibody was made to a
      peptide in the globular tail domain and the other to the globular head fragment
      of myosin V. Both antibodies inhibited vesicle transport on actin filaments by
      greater than 90% compared to controls. These studies provide the first direct
      evidence that ER vesicles are transported on actin filaments by myosin V. These
      data confirm the role of actin filaments in fast axonal transport and provide
      support for the dual filament model of vesicle transport.

PMID- 9763517
TI  - N-terminal domain of Gpa1 (G protein alpha) subunit) is sufficient for plasma
      membrane targeting in yeast Saccharomyces cerevisiae.
AB  - G proteins play a central role in transmitting signals from cell surface
      receptors to effector proteins inside the cell. Signaling can only occur,
      however, if all these protein components are properly assembled and localized at
      the plasma membrane. Past studies have shown that certain segments within the N
      terminal region of the G protein alpha subunit are necessary for membrane
      attachment. Here we identify a region within the yeast G alpha (Gpa1) that is
      sufficient for membrane attachment, as well as for specific targeting to the
      plasma membrane. Initially, we constructed chimeric proteins that replace the N
      terminus of mammalian Gsalpha with the corresponding sequence from Gpa1. Gsalpha
      is inefficiently targeted to the yeast plasma membrane and therefore cannot fully
      complement the loss of Gpa1. Gpa1-Gsaplha chimeras were assayed for proper
      membrane localization by functional complementation of a gpa1Delta ;) mutant, and
      by sucrose density gradient fractionation of cell membranes. Most of the chimeras
      tested, including one with only the N-terminal 7 amino acids from Gpa1, exhibited
      normal membrane targeting and complementing activity. We also fused various
      lengths of N-terminal Gpa1 sequence to glutathione-S-transferase (GST), a
      heterologous protein normally expressed in the cytoplasm. The first 67- 36- or 9
      amino acids of Gpa1 were all sufficient to direct GST specifically to the plasma
      membrane in yeast. This analysis defines the extreme N terminus of Gpa1 as the
      primary determinant of proper membrane targeting, and represents an essential
      step towards isolating and identifying G protein-targeting proteins within the
      plasma membrane.

PMID- 9763519
TI  - Jeffrey M. hoeg 

PMID- 9763518
TI  - Axonal outgrowth of cultured neurons is not limited by growth cone competition.
AB  - We have examined the question of scarcity-driven competition for outgrowth among
      growth cones of a single neuron. We measured spontaneous neurite elongation rates
      from 85 hours of videotape of the arbors of 31 chick sensory neurons in culture.
      These rate measurements were analyzed in ten minute periods that allowed cell
      bodies to be classified as to the number of their growth cones and the elongation
      to be analyzed as a series of discrete events. Comparing periods in which neurons
      maintained simple bipolar morphology we find no temporal competition between the
      two growth cones. That is, periods of above-average growth by one growth cone are
      not compensated by below-average growth during the same period by its sibling
      growth cone. Analyzing all outgrowth from a neuron based on its number of growth
      cones shows that net elongation rate from a single cell body is a linear function
      of the number of growth cones from 1 to 11. These observations suggest that
      growth cones behave independently and are not limited by availability of
      structural precursors. A surplus pool of structural precursors available for
      normal growth is also indicated by the high capacity for growth from single
      neurites when experimentally stimulated by mechanical tension. In addition,
      towing one or more neurites at above average rates does not cause any decline in
      simultaneous growth cone-mediated outgrowth from a single neuron compared to the
      2-3 hour period prior to experimentally induced elongation. This high capacity
      for growth combined with the often observed, intermittant growth behavior of
      individual growth cones suggests that neurite outgrowth is intrinsically limited
      primarily by poor growth cone 'performance,' not scarcity-driven competition. We
      postulate that growth cones are poor 'tractors,' exerting too little tension to
      exploit the available capacity for axonal elongation.

PMID- 9763520
TI  - AHA journals lead with definitive new online site 

PMID- 9763521
TI  - Apoptosis in the atherosclerotic plaque: quantitative and qualitative aspects.
AB  - Several laboratories have demonstrated the presence of apoptotic cell death in
      atherosclerotic plaques. Apoptosis occurs in at least 2 stages. The final
      "execution" phase, which includes DNA fragmentation, is brief ( approximately 6
      hours) and irreversible and can be detected by the terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling (TUNEL) technique. The TUNEL
      technique is only selective (rather than specific) for apoptotic nuclei, because
      these contain a far greater degree of DNA fragmentation than do nonapoptotic
      nuclei. Nonapoptotic cell nuclei that show high levels of RNA synthesis and
      splicing can also be labeled. This could explain the large variation in the
      reported percentages of TUNEL-positive nuclei in the plaques. Therefore, the
      TUNEL technique should be combined with additional techniques, such as markers of
      transcription and morphological criteria. Recent studies indicate that human
      fatty streaks differ from adaptive intimal thickenings by the presence of cells
      containing pro-apoptotic proteins. However, apoptotic cell death is present only
      in advanced atherosclerotic plaques that show a dense macrophage infiltration.
      This indicates that although both smooth muscle cells and macrophages within the
      human fatty streaks become susceptible to apoptosis, additional factors (mainly
      macrophage- and lipid-derived factors) are necessary to terminate the cell death
      pathway.

PMID- 9763522
TI  - Sphingolipids in atherosclerosis and vascular biology.
AB  - Sphingolipids and their metabolic products are now known to have second-messenger
      functions in a variety of cellular signaling pathways. Lactosylceramide (LacCer),
      a glycosphingolipid (GSL) present in vascular cells such as endothelial cells,
      smooth muscle cells, macrophages, neutrophils, platelets, and monocytes,
      contributes to atherosclerosis. Large amounts of LacCer accumulate in fatty
      streaks, intimal plaque, and calcified intimal plaque, along with oxidized low
      density lipoproteins (Ox-LDLs), growth factors, and proinflammatory cytokines. A
      possible role for LacCer in vascular cell biology was suggested when this GSL was
      found to stimulate the proliferation in vitro of aortic smooth muscle cells
      (ASMCs). A further link of LacCer in atherosclerosis was uncovered by the finding
      that Ox-LDLs stimulated specifically the biosynthesis of LacCer. Ox-LDL
      stimulated endogenous synthesis of LacCer by activation of UDP-Gal:GlcCer,beta1
      4galtransferase (GalT-2) is an early step in this signaling pathway. In turn,
      LacCer serves as a lipid second messenger that orchestrates a signal transduction
      pathway, ultimately leading to cell proliferation. This signaling pathway
      includes LacCer-mediated activation of NADPH oxidase that produces superoxide.
      Such superoxide molecules stimulate the GTP loading of p21(ras). Subsequently,
      the kinase cascade (Raf-1, Mek2, and p44MAPK [mitogen-activated protein kinase])
      is activated. The phosphorylated form of p44MAPK translocates from the cytoplasm
      to the nucleus and engages in c-fos expression, proliferating cell nuclear
      antigen (PCNA) such as cyclin activation, and cell proliferation takes place.
      Interestingly, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP),
      an inhibitor of GalT-2, can abrogate the Ox-LDL-mediated activation of GalT-2,
      the signal kinase cascade noted above, as well as cell proliferation. Additional
      studies have revealed that LacCer mediates the tumor necrosis factor-alpha (TNF
      alpha)-induced nuclear factor-kappaB expression and intercellular adhesion
      molecule (ICAM-1) expression in vascular endothelial cells via the redox
      dependent transcriptional pathway. LacCer also stimulates the expression of
      CD11/CD8, or Mac-1, on the surface of human neutrophils. Collectively, this
      phenomenon may contribute to the adhesion of neutrophils or monocytes to the
      endothelial cell surface and thus initiate the process of atherosclerosis. In
      addition, the LacCer-mediated proliferation of ASMCs may contribute to the
      progression of atherosclerosis. On the other hand, programmed cell death
      (apoptosis) by proinflammatory cytokines such as TNF-alpha, interleukin-1, and
      high concentrations of Ox-LDL occur via activation of a cell membrane-associated
      neutral sphingomyelinase (N-SMase). N-SMase hydrolyzes sphingomyelin into
      ceramide and phosphocholine. In turn, ceramide or a homologue serves as an
      important stress-signaling molecule. Interestingly, an antibody against N-SMase
      can abrogate Ox-LDL- and TNF-alpha-induced apoptosis and therefore may be useful
      for in vivo studies of apoptosis in experimental animals. Because plaque
      stability is an integral aspect of atherosclerosis management, activation of N
      SMase and subsequent apoptosis may be vital events in the onset of plaque
      rupture, stroke, or heart failure. Interestingly, in human liver cells, N-SMase
      action mediates the TNF-alpha-induced maturation of the sterol regulatory-element
      binding protein. Moreover, a cell-permeable ceramide can reconstitute the
      phenomenon above in a sterol-independent fashion. Such findings may provide new
      avenues for therapy for patients with atherosclerosis. The findings described
      here indicate an important role for sphingolipids in vascular biology and provide
      an exciting opportunity for further research in vascular disease and
      atherosclerosis.

PMID- 9763523
TI  - Polymorphonuclear leukocytes induce PDGF release from IL-1beta-treated
      endothelial cells: role of adhesion molecules and serine proteases.
AB  - Polymorphonuclear leukocytes (PMNs) and endothelial cells interact at sites of
      vascular injury during inflammatory response and during the development of
      atherosclerotic lesions. Such close proximity leads to the modulation of several
      of the biological functions of the 2 cell types. Because we have shown previously
      that PMNs enhance release of growth factors from resting endothelial cells, we
      decided to evaluate whether coincubation of PMNs with interleukin-1beta (IL
      1beta)-stimulated human umbilical vein endothelial cells (HUVEC) could further
      modulate mitogen release from HUVEC. We found that PMN-HUVEC coincubation
      resulted in a 10-fold increase in mitogen release, compared with HUVEC alone
      (14+/-6 versus 1.3+/-0.1). When PMNs were incubated with IL-1beta-treated HUVEC,
      a further increase in mitogen release (up to 35-fold) was observed. The mitogenic
      activity was immunologically related to platelet-derived growth factor (PDGF)
      because the activity was abolished by an anti-PDGF antibody. PDGF-AB antigen,
      detected in low concentrations in conditioned medium from HUVEC alone, was
      increased 4-fold when IL-1beta or PMNs were incubated with HUVEC and dramatically
      upregulated (up to 40-fold) when PMNs were cocultured with IL-1beta-treated
      HUVEC. The presence of the protease inhibitor eglin C abolished mitogenic
      activity generation, suggesting a role for PMN-derived elastase and cathepsin G.
      Indeed, purified elastase and cathepsin G mimicked PMN-induced mitogen release
      from HUVEC. Because PMNs firmly adhered to IL-1beta-treated HUVEC, we
      investigated the role of cell-cell adhesion in mitogen release. Adhesion and PDGF
      release were inhibited by approximately 60% in the presence of anti-CD11a/CD18
      and anti-intercellular adhesion molecule-1 monoclonal antibodies. This study
      suggests a new role for PMNs and their interaction with endothelium in
      pathological conditions in which intimal hyperplasia is a common feature.

PMID- 9763525
TI  - Impaired insulin-stimulated glucose oxidation and free fatty acid suppression in
      patients with familial combined hyperlipidemia: a precursor defect for
      dyslipidemia?
AB  - Familial combined hyperlipidemia (FCHL) is characterized by hyperlipidemia and
      insulin resistance, but intracellular defect in insulin action is unknown.
      Therefore, we investigated insulin action by applying the hyperinsulinemic
      euglycemic clamp technique with indirect calorimetry in 58 FCHL family members
      (28 with FCHL; 30 without dyslipidemia; aged 49+/-12 years; body mass index
      [BMI], 25. 2+/-4.0 kg/m2) and in 72 healthy control subjects (aged 54+/-6 years;
      BMI, 26.3+/-3.1 kg/m2). In the fasting state, FCHL patients had higher levels of
      total cholesterol, total triglycerides, and apolipoprotein B than control
      subjects (P<0.001 after adjustment for gender, age, and BMI). During the
      euglycemic clamp, FCHL patients had lower rates of glucose oxidation (15.93+/
      3.55 versus 19.65+/-4. 60 micromol/kg/min; P=0.001) and higher rates of lipid
      oxidation (0. 15+/-0.13 versus 0.01+/-0.25 mg/kg/min; P=0.024), as well as higher
      levels of serum-free fatty acids (FFA) (0.24+/-0.17 versus 0.06+/-0. 06 mmol/L;
      P<0.001) compared with those of control subjects. Relatives without dyslipidemia
      differed similarly from control subjects with respect to rates of glucose and
      lipid oxidation and FFA suppression during the hyperinsulinemic clamp. In FCHL
      family members, during the euglycemic clamp FFAs correlated negatively with the
      rates of glucose oxidation (P<0.001) but not with the rates of glucose
      nonoxidation (P=0.408). In FCHL family members without dyslipidemia and in
      control subjects, FFAs during the clamp correlated positively with levels of
      total triglycerides (P<0.001) and very low density lipoprotein cholesterol
      (P=0.008). We conclude that in patients with FCHL, and also in their first-degree
      relatives, insulin's suppressive effect on FFA levels is impaired, which may
      precede dyslipidemia in FCHL.

PMID- 9763524
TI  - Ligand specificity of LOX-1, a novel endothelial receptor for oxidized low
      density lipoprotein.
AB  - Endothelial dysfunction, or activation, elicited by oxidized low density
      lipoprotein (Ox-LDL) and its lipid constituents has been shown to play a key role
      in the pathogenesis of atherosclerosis. We recently have identified a novel
      receptor for Ox-LDL-designated lectin-like Ox-LDL receptor (LOX-1) in vascular
      endothelial cells. To examine ligand specificity of LOX-1, we established CHO
      cell lines stably expressing both human and bovine LOX-1 (LOX-1-CHO). LOX-1-CHO
      bound and degraded 125I-labeled Ox-LDL but did not significantly degrade 125I
      labeled acetylated LDL (Ac-LDL). Fucoidin and maleylated BSA (M-BSA), which
      inhibit 125I-Ox-LDL binding to class A scavenger receptors, did not inhibit 125I
      Ox-LDL binding or degradation in LOX-1-CHO. Polyinosinic acid and carrageenan, in
      contrast, significantly reduced 125I-Ox-LDL binding to LOX-1-CHO by 62% and 60%,
      respectively. Delipidated and untreated 125I-Ox-LDL were bound and degraded
      equally in LOX-1-CHO; furthermore, excess amounts of unlabeled, delipidated Ox
      LDL inhibited binding and degradation of untreated 125I-Ox-LDL. Taken together,
      LOX-1 is a receptor for Ox-LDL but not for Ac-LDL. LOX-1 recognizes protein
      moiety of Ox-LDL, and its ligand specificity is distinct from other receptors for
      Ox-LDL, including class A and B scavenger receptors.

PMID- 9763526
TI  - Early atherosclerotic lesions spiraling through the femoral artery.
AB  - Atherosclerosis is common in the adductor hiatus region. The aim of this study
      was to evaluate atherosclerosis in relation to themorphological structure of the
      femoropopliteal region. Two anatomic features are thought to play an important
      role in the origin of these lesions: (1) curvature of the vessel, which may lead
      to unfavorable local hemodynamic factors that change during leg flexion; and (2)
      abrupt changes in stiffness of surrounding tissues of the vessel. The distal part
      of 23 postmortem femoral arteries were investigated. Cross sections were obtained
      every 1 mm over a length of 100 mm. For each cross section, lesion thickness was
      measured at 12 points along the circumference of the vessel. No apparent relation
      was found between surrounding structures of the femoral artery and location of
      atherosclerotic lesions. Three-dimensional reconstructions showed that
      atherosclerotic lesions were spiraling through the artery in 18 of 23 cases.
      Spiraling atherosclerotic lesions may be consistent with expected flow patterns
      in this part of the femoral artery.

PMID- 9763527
TI  - Segregation analysis of plasminogen activator inhibitor-1 and fibrinogen levels
      in the NHLBI family heart study.
AB  - Elevated plasminogen activator inhibitor-1 (PAI-1) and fibrinogen concentrations
      are risk factors for coronary heart disease. We investigated environmental,
      familial, and genetic influences on PAI-1 antigen and fibrinogen concentrations
      in 2029 adults from 512 randomly ascertained families in 4 US communities. We
      used maximum-likelihood segregation analysis to fit several genetic and
      nongenetic modes of inheritance to the data to determine whether mendelian
      inheritance of a major gene could best explain the familial distributions of
      these 2 hemostatic factors. Age- and gender-adjusted familial correlations for
      PAI-1 antigen level averaged 0.16 in first-degree relatives (95% CI=0.11 to
      0.21); the spouse correlation was positive but not statistically significant
      (r=0.10, 95% CI=-0.02 to 0.23). Complex segregation analysis indicated a major
      gene associated with higher PAI-1 concentrations in 65% of individuals from these
      families. Demographic, anthropometric, lifestyle, and metabolic characteristics
      together explained 37% to 47% of the variation in PAI-1 antigen levels, and the
      inferred major gene explained an additional 17% of the variance. Positive and
      statistically significant age- and gender-adjusted familial correlations in first
      degree relatives indicated a possible heritable component influencing plasma
      fibrinogen concentration (r=0. 17, 95% CI=0.13 to 0.22); however, segregation
      analysis did not provide statistical evidence of a major gene controlling
      fibrinogen level. These family data suggest that there are modest familial and
      genetic effects on the concentration of PAI-1.

PMID- 9763528
TI  - Expression of ACAT-1 protein in human atherosclerotic lesions and cultured human
      monocytes-macrophages.
AB  - The acyl coenzyme A:cholesterol acyltransferase (ACAT) gene was first cloned in
      1993 (Chang et al, J Biol Chem. 1993;268:20747-20755; designated ACAT-1). Using
      affinity-purified antibodies raised against the N-terminal portion of human ACAT
      1 protein, we performed immunohistochemical localization studies and showed that
      the ACAT-1 protein was highly expressed in atherosclerotic lesions of the human
      aorta. We also performed cell-specific localization studies using double
      immunostaining and showed that ACAT-1 was predominantly expressed in macrophages
      but not in smooth muscle cells. We then used a cell culture system in vitro to
      monitor the ACAT-1 expression in differentiating monocytes-macrophages. The ACAT
      1 protein content increased by up to 10-fold when monocytes spontaneously
      differentiated into macrophages. This increase occurred within the first 2 days
      of culturing the monocytes and reached a plateau level within 4 days of
      culturing, indicating that the increase in ACAT-1 protein content is an early
      event during the monocyte differentiation process. The ACAT-1 protein expressed
      in the differentiating monocytes-macrophages was shown to be active by enzyme
      assay in vitro. The high levels of ACAT-1 present in macrophages maintained in
      culture can explain the high ACAT-1 contents found in atherosclerotic lesions.
      Our results thus support the idea that ACAT-1 plays an important role in
      differentiating monocytes and in forming macrophage foam cells during the
      development of human atherosclerosis.

PMID- 9763529
TI  - Estradiol suppresses MCP-1 expression In vivo : implications for atherosclerosis.
AB  - The mechanisms by which 17beta-estradiol retards atherogenesis are not known. The
      adhesion of monocytes to endothelial cells followed by the migration of monocytes
      into the artery wall are key cellular events that occur throughout the entire
      atherogenic process and may be responsive to estradiol. Monocyte chemoattractant
      protein-1 (MCP-1), a chemokine that is expressed in atherosclerotic lesions, is
      thought to play a major role in stimulating the migration of blood monocytes into
      developing atherosclerotic lesions. We therefore assessed the effects of
      estradiol in vivo on MCP-1 protein and mRNA expression in the descending thoracic
      aorta of rabbits fed a cholesterol-enriched (0.5%) diet for 6 weeks and in
      animals fed normal chow. MCP-1 protein was quantified by Western blot analysis
      and monocyte chemotaxis bioassay, and reverse transcription-polymerase chain
      reaction was used to ascertain the level of MCP-1 mRNA expression. We observed
      that in both ovary-intact and ovariectomized (OVX) animals, MCP-1 protein and
      mRNA expression were significantly increased by 6 weeks in animals fed a high
      cholesterol diet. The cholesterol-induced increase in MCP-1 protein and mRNA
      expression was significantly attenuated in OVX rabbits supplemented with
      estradiol pellets (1.5- and 10.0-mg 60-day-release pellets), which yielded a
      range of estradiol concentrations encompassing the physiological levels. MCP-1
      protein and mRNA expression were increased in normocholesterolemic OVX rabbits
      compared with normocholesterolemic ovary-intact animals, and this increase was
      prevented in OVX animals supplemented with estradiol pellets. Our observations
      indicate that both basal and hypercholesterolemia-induced increases in MCP-1
      protein are modulated by physiological concentrations of estradiol.

PMID- 9763530
TI  - Hypercholesterolemia enhances oxidant production in mesenteric venules exposed to
      Ischemia/Reperfusion.
AB  - It has been shown that hypercholesterolemia (HCh) exaggerates the microvascular
      dysfunction that is elicited by ischemia and reperfusion (I/R). The objective of
      this study was to determine whether oxidants contribute to the exaggerated
      inflammatory responses and enhanced albumin leakage observed in HCh rat
      mesenteric venules exposed to I/R (10 minutes of ischemia and 30 minutes of
      reperfusion). Intravital videomicroscopy was used to quantify the number of
      adherent and emigrated leukocytes, albumin extravasation, platelet-leukocyte
      aggregation in postcapillary venules, and the degranulation of adjacent mast
      cells. Oxidation of the fluorochrome dihydrorhodamine 123 (DHR) was used to
      monitor oxidant production by venular endothelium. I/R was shown to elicit an
      increased DHR oxidation in venules of both control and HCh rats, with the latter
      group exhibiting a significantly larger response. Treatment with either
      oxypurinol or superoxide dismutase largely prevented the leukocyte recruitment,
      platelet-leukocyte aggregation, mast cell degranulation, and enhanced DHR
      oxidation elicited by I/R in HCh rats. The enhanced albumin leakage was reduced
      by superoxide dismutase but not by oxypurinol. These results indicate that HCh
      amplifies the oxidant stress elicited by I/R and that interventions that blunt
      the oxidant stress effectively attenuate the leukocyte, platelet, and mast cell
      activation that result from I/R.

PMID- 9763531
TI  - Cholesterol metabolism and efflux in human THP-1 macrophages.
AB  - This study has investigated in detail factors regulating accumulation,
      esterification, and mobilization of cholesterol in human THP-1 macrophages. Human
      THP-1 monocytes were differentiated into macrophages and then cholesterol
      enriched by exposure to acetylated LDL (AcLDL), together with [3H]free
      cholesterol (FC). Although THP-1 macrophages accumulated FC and esterified
      cholesterol (EC), assessed by both mass and radioactivity, cellular EC always
      demonstrated a much lower specific activity (cpm/ microg) than did cellular FC,
      and several potential causes of this finding were investigated. Inhibition of
      acyl-CoA:cholesterol acyltransferase (ACAT) during loading decreased cell [3H]EC
      by 95+/-1.4% but decreased cell EC mass by only 66.0+/-4.0%, indicating that some
      intracellular undegraded AcLDL-derived EC was present in these cells.
      Esterification of [3H]oleate to EC in THP-1 cells loaded with AcLDL was 2.0 nmol
      x mg-1 x h-1, consistent with previous literature. However, EC, triglyceride, and
      phospholipid fractions respectively contained 1.0+/-0.07%, 80.0+/-0.5%, and
      18.9+/-0.3% of cell [3H]oleate, indicating triglycerides were much more
      metabolically active than EC. In addition, the mass of triglyceride in THP-1
      macrophages exceeded that of EC both before and after exposure to AcLDL.
      Esterification of nonlipoprotein-derived cholesterol was compared in THP-1 cells
      and nonhuman Fu5AH, CHO, and RAW macrophage cells. Whereas the nonhuman cell
      lines all esterified over 30% of 2-hydroxypropyl-beta-cyclodextrin (hp-ss-CD)
      delivered cholesterol within 6 hours, THP-1 cells esterified <8.0% of
      incorporated cholesterol. Kinetics of cholesterol efflux from AcLDL-loaded THP-1
      cells were first investigated after loading with only FC, and interactions
      between efflux and EC hydrolysis were further assessed after loading cells with
      both EC and FC. Over 24 hours, human apolipoprotein (apo) A-I, apoHDL
      reconstituted with phosphatidylcholine, and HDL3 respectively removed 46.6+/
      3.7%, 61. 3+/-3.4%, and 76.4+/-10.1% of [3H]FC from FC-enriched THP-1 cells.
      Cholesterol efflux to apoA-I was saturated by 24 hours and was enhanced by using
      apoA-I-phospholipid instead of pure apoA-I. Kinetic modeling identified that 97%
      of effluxed FC derived from a slow pool, with a T1/2 ranging from 27.7 hours for
      HDL to 69.3 hours for apoA-I. Although efflux enhanced net clearance of EC,
      hydrolysis of EC during concurrent inhibition of ACAT was unaffected by
      cholesterol efflux. Supplementation of THP-1 cultures with cAMP to stimulate
      hormone-sensitive lipase did not significantly enhance net hydrolysis of EC or
      cholesterol efflux. In conclusion, human THP-1 macrophages contain a large and
      metabolically active pool of triglyceride and a relatively inactive pool of EC.
      The low specific activity of EC relative to FC is contributed to by reduced
      esterification of FC, slow hydrolysis of EC, and accumulated lipoprotein EC. The
      relative inactivity of the EC pool may further contribute to already impaired
      cholesterol efflux from these cells. Net cholesterol efflux from human
      macrophages is achieved by pure apoA-I and is substantially further enhanced by
      the presence of phospholipid in acceptor particles.

PMID- 9763532
TI  - Mutations in the low-density lipoprotein receptor gene in Chinese familial
      hypercholesterolemia patients.
AB  - It has been reported that in China, patients with heterozygous familial
      hypercholesterolemia (FH) may go unrecognized because they do not have xanthomata
      or premature coronary heart disease and their LDL cholesterol levels are lower
      than those in their Western counterparts. However, in the Chinese patients in
      Hong Kong, heterozygous FH appears to manifest in a way similar to that seen in
      Western countries or Japan. We studied sequence variations in the promoter and
      coding regions of the 18 exons of the LDL receptor gene in 30 Chinese FH
      patients. Eighteen mutations were identified in 21 patients scattered in the
      promoter and 10 exons. Eleven of them were first found in this study. We also
      found 6 polymorphisms with allelic frequencies different from those in whites but
      similar to the Japanese, indicating some isolation between white and Oriental
      populations. A total of 29 mutations in the LDL receptor gene are now known in
      the Chinese. There is no definite common mutation due to a founder effect.
      Meanwhile, there were no detectable LDL receptor gene mutations in 9 clinically
      diagnosed FH patients in whom the R3500Q mutation in apolipoprotein B had also
      been excluded. The gene defects leading to the FH phenotype in these patients may
      occur somewhere else in the apolipoprotein B or other related genes, or even in
      the noncoding sequences of the LDL receptor gene.

PMID- 9763533
TI  - Postprandial lipemic response is modified by the polymorphism at codon 54 of the
      fatty acid-binding protein 2 gene.
AB  - Polymorphism of the fatty acid-binding protein 2 (FABP2) gene has been shown to
      affect the affinity of intestinal FABP for fatty acids. This could cause changes
      in postprandial triglyceride metabolism. In the present study, postprandial
      lipemia was studied in normotriglyceridemic subjects with genetic variation in
      the FABP2 gene. Oral fat-loading tests were performed in 8 subjects homozygous
      for the Thr-encoding allele at codon 54 of the FABP2 gene and in 7 subjects
      homozygous for the Ala-encoding allele (wild type). There were no significant
      differences between these 2 groups in age, body mass index, fasting plasma
      triglyceride and cholesterol levels, or fasting glucose and insulin levels. The
      increase of plasma triglyceride concentration after the fat test meal was
      significantly greater in subjects who were homozygous for the Thr-54 allele (area
      under the response curve, 4.27+/-1.31 versus 2.49+/-1.18 mmol/L x h-1, P=0.04).
      The difference was seen in both chylomicron (2.51+/-0. 98 versus 1.41+/-0.74
      mmol/L x h-1, P=0.03) and very low-density lipoprotein triglycerides (1.57+/-0.77
      versus 0.99+/-0.40 mmol/L x h-1, P=0.04). Postprandial triglyceride response
      correlated with fasting triglycerides in the Ala-54 homozygotes (r=0.79, P=0.05)
      but not in the Thr-54 homozygotes (r=0.09), who showed a strong correlation
      between triglyceride and insulin responses (r=0.83, P=0. 02). With reservations
      related to a small number of subjects studied, these results indicate that the
      Thr-encoding allele of the FABP2 gene is associated with increased postprandial
      lipemia. The lipemic response was associated with postprandial insulin response,
      suggesting that in the Thr-54 homozygotes, altered postprandial lipemia may also
      modify insulin action or vice versa.

PMID- 9763534
TI  - The gln-Arg192 polymorphism of human paraoxonase gene is not associated with
      coronary artery disease in italian patients.
AB  - Serum paraoxonase (PON) is an HDL-bound enzyme protecting LDL from oxidation. A
      common polymorphism of the paraoxonase gene (PON1) involving a Gln-to-Arg
      interchange at position 192 has been demonstrated to modulate PON activity toward
      paraoxon, a nonphysiological substrate; Arg192 (allele B) is associated with
      higher activity than Gln192 (allele A). This polymorphism has been proposed as a
      genetic marker of risk for coronary artery disease (CAD). However, the
      relationships between codon 192 PON1 genotypes, coronary atherosclerosis, and the
      occurrence of myocardial infarction (MI) are still controversial. PON1 genotypes
      were determined in 472 consecutive subjects (>40 years old) who underwent
      coronary angiography. CAD (>50% stenosis) was detected in 310 subjects (CAD+);
      162 subjects with <10% stenosis served as controls (CAD-). We also evaluated 204
      randomly selected individuals as population controls. PON1 genotypes were
      determined by PCR and AlwI restriction enzyme digestion. Frequencies of alleles A
      and B were 0. 70 and 0.30 in angiographically assessed subjects and 0.73 and 0.27
      in population controls, respectively (chi2=2.0; P<0.3). Distribution of PON1
      genotypes in CAD+ were not significantly different from those in CAD- (chi2=2.10;
      P<0.3). Similarly, no differences were observed in the subgroup of CAD+ with MI
      nor in that at higher oxidative risk (smokers and/or diabetics). After
      controlling for other coronary risk factors, no association was found between
      PON1 alleles and the presence of CAD. PON1 AA genotype was associated with
      reduced concentration of apolipoprotein B-containing triglyceride-rich
      lipoproteins. This study did not provide evidence of a significant association
      between codon 192 PON1 genotypes and coronary atherosclerosis in Italian
      patients. However, it did confirm that the PON1 low-activity allele is associated
      with a less atherogenic lipid profile.

PMID- 9763535
TI  - Paraoxonase active site required for protection against LDL oxidation involves
      its free sulfhydryl group and is different from that required for its
      arylesterase/paraoxonase activities: selective action of human paraoxonase
      allozymes Q and R.
AB  - Human serum paraoxonase (PON 1) exists in 2 major polymorphic forms (Q and R),
      which differ in the amino acid at position 191 (glutamine and arginine,
      respectively). These PON allozymes hydrolyze organophosphates and aromatic
      esters, and both also protect LDL from copper ion-induced oxidation. We have
      compared purified serum PONs of both forms and evaluated their effects on LDL
      oxidation, in respect to their arylesterase/paraoxonase activities. Copper ion
      induced LDL oxidation, measured by the production of peroxides and aldehydes
      after 4 hours of incubation, were reduced up to 61% and 58%, respectively, by PON
      Q, but only up to 46% and 38%, respectively, by an equivalent concentration of
      PON R. These phenomena were PON-concentration dependent. Recombinant PON Q and
      PON R demonstrated similar patterns to that shown for the purified serum
      allozymes. PON Q and PON R differences in protection of LDL against oxidation
      were further evaluated in the presence of glutathione peroxidase (GPx). GPx (0.1
      U/mL) alone reduced copper ion-induced LDL oxidation by 20% after 4 hours of
      incubation. The addition of PON R to the above system resulted in an additive
      inhibitory effect on LDL oxidation, whereas PON Q had no such additive effect.
      The 2 PON allozymes also differed by their ability to inhibit initiation, as well
      as propagation, of LDL oxidation. PON Q was more efficient in blocking LDL
      oxidation if added when oxidation was initiated, whereas PON R was more potent
      when added 1 hour after the initiation of LDL oxidation. These data suggest that
      the 2 allozymes act on different substrates. Both PON allozymes were also able to
      reduce the oxidation of phospholipids and cholesteryl ester. PON Q arylesterase
      activity was reduced after 4 hours of LDL oxidation by only 28%, whereas the
      arylesterase activity of PON R was reduced by up to 55%. Inactivation of the
      calcium-dependent PON arylesterase activity by using the metal chelator EDTA, or
      by calcium ion removal on a Chelex column, did not alter PON's ability to inhibit
      LDL oxidation. However, blockage of the PON free sulfhydryl group at position 283
      with p-hydroxymercuribenzoate inhibited both its arylesterase activity and its
      protection of LDL from oxidation. Recombinant PON mutants in which the PON free
      sulfhydryl group was replaced by either alanine or serine were no longer able to
      protect against LDL oxidation, even though they retained paraoxonase and
      arylesterase activities. Overall, these studies demonstrate that PON's
      arylesterase/paraoxonase activities and the protection against LDL oxidation do
      not involve the active site on the enzyme in exactly the same way, and PON's
      ability to protect LDL from oxidation requires the cysteine residue at position
      283.

PMID- 9763536
TI  - Matrix metalloproteinase-2 production and its binding to the matrix are increased
      in abdominal aortic aneurysms.
AB  - Degradation of the elastic media is a hallmark of abdominal aortic aneurysms
      (AAAs). We examined the expression of 2 elastolytic matrix metalloproteinases
      (MMPs), MMP-2 and MMP-9, in AAA aortic tissues compared with those from
      atherosclerotic occlusive disease (AOD) and nondiseased control tissues.
      Quantitative competitive reverse transcription-polymerase chain reaction and
      gelatin zymography showed increased MMP-9 mRNA and protein in both AAA and AOD
      tissues compared with those in control tissue, but there was no significant
      difference between AAA and AOD. In contrast, MMP-2 mRNA and protein levels were
      significantly higher in AAA than in AOD or control tissues. Sequential extraction
      of the MMPs from the aortic tissue with a physiological salt solution, 2%
      dimethylsulfoxide (DMSO), and 10 mol/L urea showed that large amounts of MMP-2
      and MMP-9 were bound to the matrix. The most conspicuous finding was that the
      levels of MMP-2 were significantly elevated in the DMSO fraction in AAA tissues
      compared with AOD and control tissues. In addition, a large portion of MMP-2
      found in the DMSO and urea fractions was in the active 62-kDa form, indicating
      that the precursor of MMP-2 in AAA is largely activated locally and binds to the
      tissue matrix tightly. By immunolocalization, MMP-9 was found to be primarily
      produced by macrophages and MMP-2 by mesenchymal cells. The production of MMP-2
      was prominent when mesenchymal cells were surrounded by inflammatory cells,
      suggesting paracrine modulation of MMP-2 expression in AAAs. These observations
      emphasize that MMP-2 participates in the progression of AAAs by degrading aortic
      tissue matrix components.

PMID- 9763537
TI  - Concentration of endogenous tPA antigen in coronary artery disease: relation to
      thrombotic events, aspirin treatment, hyperlipidemia, and multivessel disease.
AB  - Tissue plasminogen activator (tPA) is the major plasminogen activator responsible
      for dissolving blood clots found in blood vessels. However, elevated
      concentrations of tPA antigen were found to be related to adverse events in
      patients with coronary artery disease (CAD). Considerable controversy about the
      significance of these results exists. The goal of this cross-sectional study was
      to identify independent determinants for tPA antigen concentrations in patients
      with CAD, to possibly clarify the above paradoxical relationship. The baseline
      tPA antigen concentrations of 366 patients with angiographic evidence of coronary
      sclerosis were determined. Univariate analysis showed that age (P=0.013),
      angiographic extent of disease (P<0.001), presence of angina at rest (P<0.001),
      diabetes mellitus (P=0.004), hypercholesterolemia (P=0. 045),
      hypertriglyceridemia (P=0.015), and chronic intake of nitrates (P<0.001) were
      significantly and positively related to tPA antigen concentration, while the
      chronic intake of aspirin was inversely related to tPA antigen (P<0.001). In
      addition, plasminogen activator inhibitor type 1 (PAI-1) activity was found to be
      significantly and positively associated with tPA antigen concentration (P<0.001).
      A multivariate analysis identified chronic low-dose aspirin therapy (P<0.001),
      PAI-1 activity (P<0.001), hypertriglyceridemia (P=0.005), the type of angina
      (P=0.026), multivessel disease (P=0.041), and hypercholesterolemia (P=0.043) as
      significant and independent determinants of tPA antigen. While
      hypertriglyceridemia and hypercholesterolemia both are related to the underlying
      disease, the type of angina and the number of involved vessels are linked to the
      severity and extent of disease, and all of them are indicators of a prothrombotic
      state found during the progression of CAD. In contrary, low-dose aspirin rather
      would decrease the likelihood of thrombotic events. The relation of tPA antigen
      to PAI-1 activity furthermore underlines the relation between tPA antigen
      concentration and a prothrombotic state. Therefore, the positive or-in case of
      aspirin therapy-negative correlation of these parameters with tPA antigen
      concentration would indicate that thrombus formation and simultaneous endothelial
      cell activation might be major determinants for tPA antigen concentration in CAD.

PMID- 9763538
TI  - Combination of fosinopril and pravastatin decreases platelet response to thrombin
      receptor agonist in monkeys.
AB  - Both angiotensin-converting enzyme (ACE) inhibitors and 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been shown to
      decrease cardiovascular morbidity and mortality. Results from clinical trials
      have suggested that HMG-CoA reductase inhibition might exert a beneficial effect
      independent of its lipid-lowering effect, and ACE inhibition may exert a benefit
      independent of blood-pressure lowering. To test the hypothesis that such an
      effect might be mediated by alteration in platelet reactivity, we studied 55
      monkeys receiving both, 1, or neither of the ACE inhibitor fosinopril and the HMG
      CoA reductase inhibitor pravastatin. Platelet responsiveness to collagen and to
      the thrombin receptor agonist (TRA) SFLRRN-NH2 was determined by aggregometry.
      For each agonist, the maximum rate and extent of aggregation were measured for
      each dose, and the concentration required for half-maximal response (C50) was
      determined. Each drug, when given alone, slightly decreased the dose of agonist
      required to produce 50% response in the rate and extent of platelet aggregation
      relative to control. The combination of the 2 drugs, however, produced a
      significant increase in the dose of TRA required to produce 50% response in the
      rate and extent of aggregation relative to either drug alone or the control
      group. This was not true for collagen. The magnitude of the change relative to
      the control group, 47% for rate and 30% for extent of aggregation, could confer
      considerable protection by changing the threshold for thrombin-induced platelet
      aggregation and, thus, decrease thrombosis.

PMID- 9763539
TI  - In vitro-differentiated embryonic stem cell macrophages: a model system for
      studying atherosclerosis-associated macrophage functions.
AB  - Monocytes/macrophages (Mo) appear to play a critical role in the initiation and
      progression of atherosclerotic lesions. In this study, we characterized in vitro
      differentiated embryonic stem (ES) cell macrophages as a model system for
      studying atherosclerosis-associated Mo functions. Using immunofluorescence
      staining and Western analysis, we demonstrate that ES Mo express typical
      macrophage cell surface markers, as well as the known receptors for modified
      forms of low density lipoprotein (LDL), including the Mo scavenger receptors (SR
      A type I and type II), CD36, and CD68. Differentiated ES Mo specifically bind and
      degrade 125I-labeled acetylated LDL with high affinity, and their incubation with
      acetylated LDL (15 microg/mL) for 48 hours produces characteristic "foamy" Mo, as
      visualized by oil red O staining. ES Mo also express matrix-degrading
      metalloproteinases (MMP-3, MMP-9), which have been implicated in collagen
      breakdown in the fibrous cap of atherosclerotic plaques, and secrete cytokines
      (tumor necrosis factor-alpha, interleukin-6) in response to inflammatory stimuli.
      Transfection experiments, using a green fluorescent protein reporter gene, driven
      by the myeloid-specific promoter, CD11b, demonstrated that ES Mo can also be used
      to study macrophage-restricted gene expression in vitro. Taken together, these
      data demonstrate that ES Mo exhibit many properties typical of arterial lesion
      macrophages. Its ease of genetic manipulation makes it an attractive system for
      investigations of macrophage functions in vitro.

PMID- 9763540
TI  - Differential induction of cyclooxygenase-2 in human arterial and venous smooth
      muscle: role of endogenous prostanoids.
AB  - Two isoforms of cyclooxygenase (COX) have been identified: a constitutive isoform
      (COX-1), found in abundance in platelets and the vascular endothelium, and an
      "inflammatory" cytokine-inducible isoform (COX-2). Because COX metabolites
      regulate vascular smooth muscle cell (SMC) function and the interaction between
      the vessel and circulating components, we have investigated the possibility that
      COX-2 can be induced in human arterial or venous SMC. Untreated venous or
      arterial cells contained undetectable levels of COX-1 or COX-2 and released low
      levels of metabolites. After stimulation with interleukin-1beta, tumor necrosis
      factor-alpha, interferon-gamma, and bacterial lipopolysaccharide, both venous and
      arterial SMC expressed COX-2 protein and released increased amounts of
      prostaglandins. In addition, the induced release of PGE2 was inhibited by the COX
      2-selective inhibitor, L-745,337. When cells were treated with the mixture of
      cytokines, venous SMC expressed greater amounts of COX-2 protein and released
      more prostaglandins than arterial SMC. Furthermore, when COX-2 activity was
      blocked by L-745,337, COX-2 expression in arterial SMC, but not in venous SMC,
      increased. Thus, this article describes, for the first time, that COX-2 is
      expressed in greater amounts in venous SMC than in arterial SMC. Moreover, we
      show that this "differential induction" is due to a negative-feedback pathway for
      COX-2 expression in arterial SMC but not in venous SMC. The ability of COX-2
      activity to limit COX-2 expression in some cells but not others may contribute to
      the highly developed mechanisms involved in prostanoid release.

PMID- 9763541
TI  - Vitamin C protects human arterial smooth muscle cells against atherogenic
      lipoproteins: effects of antioxidant vitamins C and E on oxidized LDL-induced
      adaptive increases in cystine transport and glutathione.
AB  - Glutathione (GSH) plays a key role in cellular antioxidant defenses by scavenging
      reactive oxygen species and reducing lipid peroxides. Intracellular GSH levels
      are regulated by transport of its precursor L-cystine via system xc-, which can
      be induced by oxidant stress. As oxidatively modified low density lipoproteins
      (LDLs) contribute to impaired vascular reactivity and the formation of
      atherosclerotic lesions, we have examined the effects of oxidized LDL and the
      antioxidant vitamins C and E on the L-cystine-GSH pathway in human umbilical
      artery smooth muscle cells (HUASMCs). Oxidized LDL, but not native LDL, elevated
      intracellular GSH levels and L-cystine transport via system xc- in a time
      dependent (up to 24 hours) and dose-dependent (10 to 100 microg x mL-1) manner.
      These increases were dependent on protein synthesis and the extent of LDL
      oxidation, but the induction of L-cystine transport activity was independent of
      GSH synthesis. Pretreatment of HUASMCs for 24 hours with vitamin E (100
      micromol/L) attenuated oxidized LDL-mediated increases in GSH, whereas
      pretreatment with vitamin C depressed basal levels and abolished oxidized LDL
      induced increases in GSH and L-cystine transport in a time-dependent (3 to 24
      hours) and dose-dependent (10 to 100 micromol/L) manner. Pretreatment of cells
      with dehydroascorbate had no effect on oxidized LDL-mediated increases in L
      cystine transport and only marginally attenuated increases in GSH. Our findings
      provide the first evidence that vitamin C spares endogenous adaptive antioxidant
      responses in human vascular smooth muscle cells exposed to atherogenic oxidized
      LDL.

PMID- 9763542
TI  - Adhesion receptors as regulators of the hematopoietic process.

PMID- 9763543
TI  - The sialomucin CD164 (MGC-24v) is an adhesive glycoprotein expressed by human
      hematopoietic progenitors and bone marrow stromal cells that serves as a potent
      negative regulator of hematopoiesis.
AB  - Mucin-like molecules represent an emerging family of cell surface glycoproteins
      expressed by cells of the hematopoietic system. We report the isolation of a cDNA
      clone that encodes a novel transmembrane isoform of the mucin-like glycoprotein
      MGC-24, expressed by both hematopoietic progenitor cells and elements of the bone
      marrow (BM) stroma. This molecule was clustered as CD164 at the recent workshop
      on human leukocyte differentiation antigens. CD164 was identified using a
      retroviral expression cloning strategy and two novel monoclonal antibody (MoAb)
      reagents, 103B2/9E10 and 105.A5. Both antibodies detected CD164/MGC-24v protein
      expression by BM stroma and subpopulations of the CD34(+) cells, which include
      the majority of clonogenic myeloid (colony-forming unit-granulocyte-macrophage
      [CFU-GM]) and erythroid (blast-forming unit-erythroid [BFU-E]) progenitors and
      the hierarchically more primitive precursors (pre-CFU). Biochemical and
      functional characterization of CD164 showed that this protein represents a
      homodimeric molecule of approximately 160 kD. Functional studies demonstrate a
      role for CD164 in the adhesion of hematopoietic progenitor cells to BM stromal
      cells in vitro. Moreover, antibody ligation of CD164 on primitive hematopoietic
      progenitor cells characterized by the cell surface phenotype CD34(BRIGHT)CD38(-)
      results in the decreased recruitment of these cells into cell cycle, suggesting
      that CD164 represents a potent signaling molecule with the capacity to suppress
      hematopoietic cell proliferation.

PMID- 9763544
TI  - Cyclical neutropenia and other periodic hematological disorders: a review of
      mechanisms and mathematical models.
AB  - Although all blood cells are derived from hematopoietic stem cells, the
      regulation of this production system is only partially understood. Negative
      feedback control mediated by erythropoietin and thrombopoietin regulates
      erythrocyte and platelet production, respectively, but the regulation of
      leukocyte levels is less well understood. The local regulatory mechanisms within
      the hematopoietic stem cells are also not well characterized at this point.
      Because of their dynamic character, cyclical neutropenia and other periodic
      hematological disorders offer a rare opportunity to more fully understand the
      nature of these regulatory processes. We review the salient clinical and
      laboratory features of cyclical neutropenia (and the less common disorders
      periodic chronic myelogenous leukemia, periodic auto-immune hemolytic anemia,
      polycythemia vera, aplastic anemia, and cyclical thrombocytopenia) and the
      insight into these diseases afforded by mathematical modeling. We argue that the
      available evidence indicates that the locus of the defect in most of these
      dynamic diseases is at the stem cell level (auto-immune hemolytic anemia and
      cyclical thrombocytopenia seem to be the exceptions). Abnormal responses to
      growth factors or accelerated cell loss through apoptosis may play an important
      role in the genesis of these disorders.

PMID- 9763545
TI  - Cell cycle-related changes in repopulating capacity of human mobilized peripheral
      blood CD34(+) cells in non-obese diabetic/severe combined immune-deficient mice.
AB  - Most primitive hematopoietic progenitor cells reside in vivo within the G0/G1
      phase of the cell cycle. By simultaneous DNA/RNA staining it is possible to
      distinguish G0 and G1 states and to isolate cells in defined phases of the cell
      cycle. We report here the use of cell cycle fractionation to separate human
      mobilized peripheral blood (MPB) CD34(+) cells capable of repopulating the bone
      marrow (BM) of non-obese diabetic/severe combined immune-deficient (NOD/SCID)
      mice. In freshly isolated MPB, repopulating cells were predominant within the G0
      phase, because transplantation of CD34(+) cells residing in G0 (G0CD34(+))
      resulted on average in a 16.6- +/- 3.2-fold higher BM chimerism than infusion of
      equal numbers of CD34(+) cells isolated in G1. We then investigated the effect of
      ex vivo cell cycle progression, in the absence of cell division, on engraftment
      capacity. Freshly isolated G0CD34(+) cells were activated by interleukin-3 (IL
      3), stem cell factor (SCF), and flt3-ligand (FL) for a 36-hour incubation period
      during which a fraction of cells progressed from G0 into G1 but did not complete
      a cell cycle. The repopulating capacity of stimulated cells was markedly
      diminished compared with that of unmanipulated G0CD34(+) cells. Cells that
      remained in G0 during the 36-hour incubation period and those that traversed into
      G1 were sorted and assayed separately in NOD/SCID recipients. The repopulating
      ability of cells remaining in G0 was insignificantly reduced compared with that
      of unstimulated G0CD34(+) cells. On the contrary, CD34(+) cells traversing from
      G0 into G1 were largely depleted of repopulating capacity. Similar results were
      obtained when G0CD34(+) cells were activated by the combination of thrombopoietin
      SCF-FL. These studies provide direct evidence of the quiescent nature of cells
      capable of repopulating the BM of NOD/SCID mice. Furthermore, these data also
      demonstrate that G0-G1 progression in vitro is associated with a decrease in
      engraftment capacity.

PMID- 9763546
TI  - Integrins involved in the adhesion of megakaryocytes to fibronectin and
      fibrinogen.
AB  - We studied integrins involved in the adhesion of resting and activated
      megakaryocytes (MK) to fibronectin (FN) and fibrinogen (FGN). Guinea pig MK were
      isolated and in some experiments were activated by thrombin. MK adhering to FN or
      FGN coated on coverslips were quantitated by a computerized image analysis
      program. The binding of soluble human FN to MK was detected by Western blotting.
      Anti-integrin antibodies, disintegrins, and cyclic RGD peptides were used to
      identify integrins involved in the adhesion of MK to FN or FGN. Resting MK
      adhered to coverslips with immobilized FN. The adhesion of MK to FN was primarily
      inhibited by an anti-alpha5 antibody and EMF-10, a distintegrin highly specific
      for alpha5 beta1. However, the adhesion of MK to FN was not blocked by agents
      that inhibit alphaIIb beta3, alphav beta3 or alpha4 beta1. A beta1 activating
      antibody increased the number of MK bound to FN due to the activation of alpha5
      beta1. The binding of soluble FN was also primarily inhibited by agents that
      block alpha5 beta1. Resting MK did not adhere to FGN. However, MK activated by
      thrombin did adhere to FGN. This binding was mediated by alphaIIb beta3, because
      binding was inhibited by bitistatin, a disintegrin, and a cyclic RGD peptide that
      are known to block this integrin. The binding of thrombin-activated MK to FN was
      mediated by both alpha5 beta1 and alphaIIb beta3 based on the additive effect of
      agents that inhibit these integrins. The study indicates that resting MK bind to
      FN but not to FGN and that alpha5 beta1 is the major integrin involved in the
      binding of MK to FN. Activated MK bind to FGN primarily by alphaIIb beta3.
      However, the binding of activated MK to FN is due to both alpha5 beta1 and
      alphaIIb beta3. The demonstration that alpha5 beta1 and that alphaIIb beta3 are
      involved in MK adhesion indicates that these integrins may have a role in MK
      maturation and platelet production.

PMID- 9763547
TI  - Attenuated hematopoietic response to granulocyte-macrophage colony-stimulating
      factor in patients with acquired pulmonary alveolar proteinosis.
AB  - The pathogenesis of acquired pulmonary alveolar proteinosis (PAP), a rare lung
      disease characterized by excessive surfactant accumulation within the alveolar
      space, remains obscure. Gene-targeted mice lacking the hematopoietic growth
      factor granulocyte-macrophage colony-stimulating factor (GM-CSF) or the signal
      transducing beta-common chain of the GM-CSF receptor have impaired surfactant
      clearance and pulmonary pathology resembling human PAP. We therefore investigated
      the hematopoietic effects of GM-CSF in patients with PAP. The hematologic
      response of 5 infants with congenital PAP to 5 microgram/kg/d was of normal
      magnitude. By contrast, despite normal expression of GM-CSF receptor alpha- and
      beta-common chains on peripheral blood myelomonocytic cells (n = 6) and normal
      binding affinity of bone marrow mononuclear cells for GM-CSF (n = 3), each of the
      12 patients with acquired PAP treated displayed impaired responses to GM-CSF; 5
      microgram/kg/d produced only minor eosinophilia, and doses of 7.5 to 20
      microgram/kg were required to induce >/=1.5-fold neutrophil increments in the 3
      patients who underwent dose-escalation. However, neutrophilic responses to 5
      microgram/kg granulocyte colony-stimulating factor (G-CSF) were normal (n = 4).
      In vitro, the proportion of hematopoietic progenitors responsive to GM-CSF (16.1%
      +/- 8.9%; P = .042) or interleukin-3 (IL-3; 19.3% +/- 7.7%; P = .063), both of
      which utilize the beta-common chain of the GM-CSF receptor complex, were reduced
      among patients with acquired PAP (n = 4) compared with normal bone marrow donor
      controls (47.2% +/- 25.9% and 40.9% +/- 18.6%, respectively). In the one
      individual who had complete resolution of lung disease during the period of
      study, this was temporally associated with correction of this defective in vitro
      response to GM-CSF and IL-3 on serial assessment. These data establish that
      patients with acquired PAP have an associated impaired responsiveness to GM-CSF
      that is potentially pathogenic in the development of their lung disease. Based on
      these observations, we propose a model of the pathogenesis of acquired PAP that
      suggests the disease arises as a consequence of an acquired clonal disorder
      within the hematopoietic progenitor cell compartment.

PMID- 9763548
TI  - Divergent effects of interleukin-4 and interferon-gamma on macrophage-derived
      chemokine production: an amplification circuit of polarized T helper 2 responses.
AB  - Macrophage-derived chemokine (MDC) is a CC chemokine that recognizes the CCR4
      receptor and is selective for T helper 2 (Th2) versus T helper 1 (Th1) cells. The
      present study was designed to investigate the effect of the prototypic Th2/Th1
      cytokines, interleukin-4 (IL-4) and interferon-gamma (IFN-gamma), on the
      production of MDC by human monocytes. IL-4 and IL-13 caused a time-dependent
      (plateau at 24 hours) and concentration-dependent (EC50 2 and 10 ng/mL,
      respectively) increase of MDC mRNA levels in monocytes. Increased expression of
      MDC mRNA was associated with protein release in the supernatant. MDC expression
      and production induced by IL-4 and IL-13 were inhibited by IFN-gamma. IFN-gamma
      also suppressed the constitutive expression of MDC in mature macrophages and
      dendritic cells. These results delineate an amplification loop of polarized Th2
      responses based on differential regulation of MDC production by IL-4 and IL-13
      versus IFN-gamma and on the selectivity of this chemokine for polarized Th2
      cells.

PMID- 9763549
TI  - Activated endothelial cells induce apoptosis in leukemic cells by endothelial
      interleukin-8.
AB  - Tumor cells are eradicated by several systems, including Fas ligand-Fas and tumor
      necrosis factor (TNF)-tumor necrosis factor receptor (TNFR). In the previous
      study, we purified an apoptosis-inducing factor (AIF) to homogeneity from a
      medium conditioned by PDBu-treated HL-60 cells. N-terminal sequence analysis
      showed that AIF is identical to endothelial interleukin-8 (IL-8). A novel
      apoptosis system, in which endothelial cells participate via endothelial IL-8
      release, is identified here. Human umbilical vein cells (VE cells) produce and
      secrete IL-8 by stimulation of IL-1alpha and TNF-alpha. Endothelial IL-8, which
      is secreted from VE cells by stimulation of IL-1alpha and TNF-alpha , induces
      apoptosis in myelogenous leukemia cell line K562 cells. Monocyte-derived IL-8
      could not induce apoptosis in K562 cells. Moreover, interaction between VE cells
      and K562 cells induces the release of endothelial IL-8 from VE cells, and the
      attached K562 cells undergo apoptosis. Moreover, interactions between VE cell and
      other cell lines, such as HL-60, U937, Jurkat, and Daudi, induce the secretion of
      endothelial IL-8 and the induction of apoptosis in cell lines. Endothelial IL-8
      significantly inhibits tumor growth of intraperitoneal and subcutaneous tumor
      mass of K562 cells and induces apoptosis in their cells in vivo. Endothelial IL-8
      plays an important role in apoptosis involving endothelial cells, which may
      provide us with a new therapy for hematological malignancies.

PMID- 9763550
TI  - Molecular and serological examination of the relationship of human herpesvirus 8
      to multiple myeloma: orf 26 sequences in bone marrow stroma are not restricted to
      myeloma patients and other regions of the genome are not detected.
AB  - Human herpesvirus 8 (HHV-8) genomic sequences were recently detected by
      polymerase chain reaction (PCR) and in situ hybridization in bone marrow stromal
      cells grown from multiple myeloma (MM) patients, but not in cells from control
      subjects (Rettig et al, Science 276:1851, 1997). We sought to confirm these
      observations in our own group of MM patients (n = 30). DNA was extracted from
      adherent stromal cells grown under varying conditions and assayed for HHV-8
      sequence using PCR to amplify the orf 26 (KS330) sequence (Chang et al, Science
      266:1865, 1997), as initially reported. Samples from human control subjects (n =
      25) were concurrently extracted and analyzed. After 30 cycles of amplification,
      we did not detect any positive samples. In a more sensitive nested PCR, samples
      from 18 of 30 (60%) MM patients were positive, at about the limit of detection,
      but orf 26 sequence was also amplified from 11 of 25 (44%) human control samples.
      However, PCR amplification from other regions of the viral genome (orf 72 and orf
      75) was uniformly negative for all MM and control samples, despite equivalent
      sensitivity. Additionally, all sera from MM patients were negative for HHV-8 IgG
      by immunofluorescence. Our data do not support a role of HHV-8 in the etiology of
      MM but may suggest the presence of a related (KS330-containing) virus in MM
      patients and in some control subjects. This is a US government work. There are no
      restrictions on its use.

PMID- 9763551
TI  - The cryptic inv(2)(p23q35) defines a new molecular genetic subtype of ALK
      positive anaplastic large-cell lymphoma.
AB  - Recently, a distinctive entity characterized by expression of the anaplastic
      lymphoma kinase (ALK) protein [most frequently due to the t(2;5)(p23;q35)
      associated NPM-ALK fusion] has emerged within the heterogenous group of non
      Hodgkin's lymphomas (NHL) classified as anaplastic large-cell lymphoma (ALCL).
      Sporadic variant 2p23/ALK abnormalities identified in ALK-positive ALCL indicate
      that genes other than NPM may also be involved in the deregulation of ALK and
      lymphomagenesis. We report here three cases with an inv(2)(p23q35) detected by
      fluorescence in situ hybridization (FISH) in young male patients with ALK
      positive ALCL. In contrast to ALCL cases with the classical t(2;5)(p23;q35) that
      usually show both cytoplasmic and nuclear or predominantly nuclear alone
      localization of the NPM-ALK chimeric product, in all three cases with an
      inv(2)(p23q35) the ALK protein accumulated in the cytoplasm only, supporting the
      previous assumption that the oncogenic potential of ALK may not be dependent on
      its nuclear localization. As the first step to identify the ALK partner gene
      involved in the inv(2)(p23q35), we performed extensive FISH studies and
      demonstrated that the 2q35 breakpoint occurred within the 1,750-kb region
      contained within the 914E7 YAC. Moreover, a striking association of the
      inv(2)(p23q35) with a secondary chromosomal change, viz,
      ider(2)(q10)inv(2)(p23q35), carrying two additional copies of the putative ALK
      related fusion gene, was found in all three patients, suggesting that, in
      contrast to the standard t(2;5)/NPM-ALK fusion, multiple copies of the putative
      2q35-ALK chimeric gene may be required for efficient tumor development. In
      summary, we demonstrate that the inv(2)(p23q35), a variant of the
      t(2;5)(p23;q35), is a recurrent chromosomal abnormality in ALK-positive ALCL, the
      further characterization of which should provide new insight into the
      pathogenesis of these lymphomas.

PMID- 9763552
TI  - Antithrombins Wibble and Wobble (T85M/K): archetypal conformational diseases with
      in vivo latent-transition, thrombosis, and heparin activation.
AB  - The inherent variability of conformational diseases is demonstrated by two
      families with different mutations of the same conserved aminoacid in
      antithrombin. Threonine 85 underlies the opening of the main beta-sheet of the
      molecule and its replacement, by the polar lysine, in antithrombin Wobble,
      resulted in a plasma deficiency of antithrombin with an uncharacteristically
      severe onset of thrombosis at 10 years of age, whereas the replacement of the
      same residue by a nonpolar methionine, antithrombin Wibble, gave near-normal
      levels of plasma antithrombin and more typical adult thromboembolic disease.
      Isolated antithrombin Wibble had a decreased thermal stability (Tm 56.2, normal
      57.6 degreesC) but was fully stabilized by the heparin pentasaccharide (Tm 71.8,
      normal 71.0 degreesC), indicating that the prime abnormality is a laxity in the
      transition of the main sheet of the molecule from the 5- to 6-stranded form, as
      was confirmed by the ready conversion of antithrombin Wibble to the 6-stranded
      latent form on incubation. That this transition can occur in vivo was shown by
      the finding of nearly 10% of the proband's plasma antithrombin in the latent form
      and also, surprisingly, of small but definitive amounts of latent antithrombin in
      normal plasma. The latent transition will be predictably accelerated not only by
      gross mutations, as with antithrombin Wobble, to give severe episodic thrombosis,
      but also by milder mutations, as with antithrombin Wibble, to trigger thrombosis
      in the presence of other predisposing factors, including the conformational
      stress imposed by the raised body temperatures of fevers. Both antithrombin
      variants had an exceptional (25-fold) increase in heparin affinity and this,
      together with an increased inhibitory activity against factor Xa, provides
      evidence of the direct linkage of A-sheet opening to the conformational basis of
      heparin binding and activation.

PMID- 9763553
TI  - Treatment of acquired von Willebrand syndrome in patients with monoclonal
      gammopathy of uncertain significance: comparison of three different therapeutic
      approaches.
AB  - Patients with monoclonal gammopathies of uncertain significance (MGUS) may
      develop an acquired bleeding disorder similar to congenital von Willebrand
      disease, called acquired von Willebrand syndrome (AvWS). In these patients,
      measures to improve hemostasis are required to prevent or treat bleeding
      episodes. We diagnosed 10 patients with MGUS and AvWS: 8 had IgGkappa (3) or
      lambda (5) MGUS and 2 IgM-kappa MGUS. Three therapeutic approaches were compared
      in them: (1) desmopressin (DDAVP), (2) factor VIII/von Willebrand factor
      (FVIII/vWF) concentrate, and (3) high-dose (1 g/kg/d for 2 days) intravenous Ig
      (IVIg). In patients with IgG-MGUS, DDAVP and FVIII/vWF concentrate increased
      factor VIII and von Willebrand factor in plasma, but only transiently. IVIg
      determined a more sustained improvement of the laboratory abnormalities and
      prevented bleeding during surgery (short-term therapy). In addition to the
      standard 2-day infusion protocol, a long-term IVIg therapy was performed in 2
      patients with IgG-MGUS: repeated (every 21 days) single infusions of IVIg did
      improve laboratory abnormalities and stopped chronic gastrointestinal bleeding.
      On the other hand, IVIg failed to correct laboratories abnormalities in patients
      with IgM-MGUS. These comparative data obtained in a relative large and
      homogeneous group of patients with AvWS and MGUS confirm that DDAVP and FVIII/vWF
      concentrates improve the bleeding time (BT) and FVIII/vWF measurements only
      transiently, whereas IVIg provides a sustained treatment of AvWS associated with
      IgG-MGUS, but not with IgM-MGUS.

PMID- 9763555
TI  - Successful treatment of invasive aspergillosis in chronic granulomatous disease
      by bone marrow transplantation, granulocyte colony-stimulating factor-mobilized
      granulocytes, and liposomal amphotericin-B.
AB  - X-linked chronic granulomatous disease (X-CGD) is a primary immunodeficiency with
      complete absence or malfunction of the nicotinamide adenine dinucleotide
      phosphate (NADPH) oxidase in the phagocytic cells. Life-threatening infections
      especially with aspergillus are common despite optimal antimicrobial therapy.
      Bone marrow transplantation (BMT) is contraindicated during invasive
      aspergillosis in any disease setting. We report an 8-year-old patient with CGD
      who underwent HLA-genoidentical BMT during invasive multifocal aspergillus
      nidulans infection, nonresponsive to treatment with amphotericin-B and gamma
      interferon. During the first 10 days post-BMT, the patient received granulocyte
      colony-stimulating factor (G-CSF)-mobilized, 25 Gy irradiated granulocytes from
      healthy volunteers plus G-CSF beginning on day 3 to prolong the viability of the
      transfused granulocytes. This was confirmed in vitro by apoptosis assays and in
      vivo by finding nitroblue tetrazolium (NBT)-positive granulocytes in peripheral
      blood 12 and 36 hours after the transfusions. Clinical and biological signs of
      infection began to disappear on day 7 post-BMT. Positron emission tomography with
      F18-fluorodeoxyglucose (FDG-PET) and computed tomography (CT) scans at 3 months
      post-BMT showed complete disappearance of infectious foci. At 2 years post-BMT,
      the patient is well with full immune reconstitution and no sign of aspergillus
      infection. Our results show that HLA-identical BMT may be successful during
      invasive, noncontrollable aspergillus infection, provided that supportive therapy
      is optimal.

PMID- 9763554
TI  - Incidence, clinical features, and outcome of all trans-retinoic acid syndrome in
      413 cases of newly diagnosed acute promyelocytic leukemia. The European APL
      Group.
AB  - All trans-retinoic acid (ATRA) syndrome is a life-threatening complication of
      uncertain pathogenesis that can occur during the treatment of acute promyelocytic
      leukemia (APL) by ATRA. Since its initial description, however, no large series
      of ATRA syndrome has been reported in detail. We analyzed cases of ATRA syndrome
      observed in an ongoing European trial of treatment of newly diagnosed APL. In
      this trial, patients 65 years of age or less with an initial white blood cell
      count (WBC) less than 5,000/microL were initially randomized between ATRA
      followed by chemotherapy (CT) (ATRA-->CT group) or ATRA with CT started on day 3;
      patients with WBC greater than 5,000/microL received ATRA and CT from day 1;
      patients aged 66 to 75 received ATRA-->CT. In patients with initial WBC less than
      5, 000/microL and allocated to ATRA-->CT, CT was rapidly added if WBC was greater
      than 6,000, 10,000, 15,000/microL by days 5, 10, and 15 of ATRA treatment. A
      total of 64 (15%) of the 413 patients included in this trial experienced ATRA
      syndrome during induction treatment. Clinical signs developed after a median of 7
      days (range, 0 to 35 days). In two of them, they were in fact present before the
      onset of ATRA. In 11 patients, they occurred upon recovery from the phase of
      aplasia due to the addition of CT. Respiratory distress (89% of the patients),
      fever (81%), pulmonary infiltrates (81%), weight gain (50%), pleural effusion
      (47%), renal failure (39%), pericardial effusion (19%), cardiac failure (17%),
      and hypotension (12%) were the main clinical signs, and 63 of the 64 patients had
      at least three of them. Thirteen patients required mechanical ventilation and two
      dialysis. A total of 60 patients received CT in addition to ATRA as per protocol
      or based on increasing WBC; 58 also received high dose dexamethasone (DXM); ATRA
      was stopped when clinical signs developed in 30 patients. A total of 55 patients
      (86%) who experienced ATRA syndrome achieved complete remission (CR), as compared
      with 94% of patients who had no ATRA syndrome (P = .07) and nine (14%) died of
      ATRA syndrome (5 cases), sepsis (2 cases), leukemic resistance (1 patient), and
      central nervous system (CNS) bleeding (1 patient). None of the patients who
      achieved CR and received ATRA for maintenance had ATRA syndrome recurrence. No
      significant predictive factors of ATRA syndrome, including pretreatment WBC,
      could be found. Kaplan Meier estimates of relapse, event-free survival (EFS), and
      survival at 2 years were 32% +/- 10%, 63% +/- 8%, and 68% +/- 7% in patients who
      had ATRA syndrome as compared with 15% +/- 3%, 77% +/- 2%, and 80% +/- 2% in
      patients who had no ATRA syndrome (P = .05, P = .003, and P = .03), respectively.
      In a stepwise Cox model that also included pretreatment prognostic variables,
      ATRA syndrome remained predictive for EFS and survival. In conclusion, in this
      multicenter trial where CT was rapidly added to ATRA in case of high or
      increasing WBC counts and DXM generally also used at the earliest clinical sign,
      the incidence of ATRA syndrome was 15%, but ATRA syndrome was responsible for
      death in only 1.2% of the total number of patients treated. However, occurrence
      of ATRA syndrome was associated with lower EFS and survival.

PMID- 9763556
TI  - Efficacy and costs of granulocyte colony-stimulating factor in allogeneic T-cell
      depleted bone marrow transplantation.
AB  - Hematopoietic growth factors have shown clinical benefits in patients undergoing
      chemotherapy and stem cell transplantation, but few studies have been performed
      to assess whether the benefits are worth the costs. We reviewed 196 patients
      undergoing T-cell depleted related donor bone marrow transplantation (BMT)
      between 1990 and 1996 to assess the effect of growth factor use on time to
      engraftment and costs of hospitalization. Beginning in 1994, based on encouraging
      results in autologous transplantation, patients (n = 81) were treated with
      granulocyte colony-stimulating factor (G-CSF) starting at day +1 after marrow
      infusion until engraftment. Between January 1, 1990 and January 1, 1994, patients
      (n = 115) did not receive growth factor. CD6 depletion of donor marrow was the
      only form of prophylaxis against graft-versus-host disease (GVHD). Despite
      receiving a lower stem cell dose (P = .004), the group receiving G-CSF had a
      decreased time to engraftment (20 days v 12 days, P < .0001) and time from marrow
      infusion to discharge (23 days v 17 days, P < .0001). In multivariate modeling,
      the use of G-CSF was the most significant factor predicting time to engraftment
      and discharge. Incidence of grades II-IV GVHD, early mortality, percentage of
      patients who engrafted, and relapse rates did not differ between the groups.
      Inpatient charges during the first 50 days after marrow infusion (including
      readmissions) were available on 110 patients and were converted to costs using
      departmental ratios of costs of charges. Median costs were significantly lower in
      the group receiving G-CSF ($80,600 v $84,000, P = .0373). Thus, use of G-CSF in
      this setting allows earlier hospital discharge with lower costs.

PMID- 9763557
TI  - Philadelphia chromosome-positive (Ph+) childhood acute lymphoblastic leukemia:
      good initial steroid response allows early prediction of a favorable treatment
      outcome.
AB  - Among 4,760 acute lymphoblastic leukemia (ALL) patients enrolled from 1986 to
      1995 in two subsequent trials of the BFM and AIEOP study group, 61 patients were
      found to have Philadelphia chromosome-positive (Ph+) ALL. These patients were
      analyzed for presenting features and treatment outcome to identify specific
      prognostic factors. Treatment stratification was based on initial cell mass and
      early response as determined by blast count in peripheral blood after a 7-day
      induction prephase with prednisone and one dose of intrathecal methotrexate on
      day 1. All patients were treated by similar intensive Berlin-Frankfurt-Munster
      (BFM) protocols. The median age of Ph+ patients was 7.5 years, the median white
      blood cell count (WBC) was 75 x 10(9)/L, 77% of patients had common ALL, and 29%
      coexpressed myeloid markers. After a median observation time of 4.2 years, 29 of
      61 patients are alive (survival probability [pSUR] at 4 years, 0.49; standard
      error [SE], 0.06), and 24 of 61 are in first complete remission (CR1; probability
      of event-free survival [pEFS] at 4 years, 0.38; SE, 0.06). Twenty (35%) of 57
      evaluable patients had >/=1,000 leukemic blasts per microliter of blood on day 8
      of induction (defined as prednisone-poor-response [PPR]). These patients were
      older (10.0 v 6.88 years; P = .02) and had a higher WBC (144 v 29 x 10(9)/L; P =
      .0016) as compared with patients with prednisone good response (PGR; <1,000
      blasts/microL at day 8). Only 2 of 20 patients (10%) with PPR remained in CR1 and
      alive: 6 patients with PPR did not survive after allogeneic bone marrow
      transplantation (BMT) due to recurring disease (n = 3) and toxicity (n = 3), and
      12 nontransplanted patients died due to progression (n = 5) or relapse (n = 7).
      In contrast, 26 (70%) of the 37 patients with PGR are alive. Of 18 patients
      transplanted by allo-BMT, 1 relapsed (now in CR2) and 4 died after BMT. Among the
      19 patients with PGR treated by chemotherapy alone, 8 remained in CR1 and 11
      relapsed, of which 4 are in CR2 or CR3. The prednisone response emerged as the
      only independent prognostic factor for survival in Cox regression analysis. Thus,
      two thirds of Ph+ childhood ALL cases can be identified early by PGR, which, when
      treated with intensive BFM chemotherapy, with or without BMT, have a
      significantly lower risk of treatment failure. With a median continuous complete
      remission (CCR) time of 4.1 years, pEFS for PGR is 0.55 (SE, 0.08) compared with
      0.10 (SE, 0.07) in patients with PPR (P = .0001). PGR is also an indicator for
      treatment responsiveness and durable second remission after relapse, which in
      turn may provide a second chance for BMT.

PMID- 9763558
TI  - Decreased rejection and improved survival of first and second marrow transplants
      for severe aplastic anemia (a 26-year retrospective analysis).
AB  - Between 1970 and 1996, 333 patients with severe aplastic anemia underwent HLA
      matched related marrow transplant after conditioning with cyclophosphamide (CY).
      Thirty-five percent of patients transplanted between 1970 and 1976 (group 1), 12%
      of those transplanted between 1977 and 1981 (group 2), and 9% of patients
      transplanted between 1982 and 1997 (group 3) had graft rejection. Graft rejection
      occurred later among group 3 patients (median, 180 days) than among those in
      groups 1 and 2 (medians, 28 and 47 days, respectively; P < .001 group 3 v 2). In
      group 3, 92% of rejecting patients underwent a second transplant, compared with
      78% and 77% in groups 1 and 2, respectively. Group 1 patients received various
      conditioning regimens before second transplant, whereas most patients of groups 2
      and 3 received CY combined with antithymocyte globulin (ATG). Graft-versus-host
      disease (GVHD) prophylaxis after second transplant consisted of methotrexate
      (MTX) for all group 1 and 2 patients, whereas group 3 patients received MTX
      combined with cyclosporine (CSP). Over the three time periods studied, first
      graft rejection decreased from 35% to 9%, and the proportion of rejecting
      patients undergoing second transplants increased from 77% to 92%. The 10-year
      probability of survival after second transplants increased from 5% to 83%.
      Multivariate analysis showed MTX/CSP GVHD prophylaxis to be a significant factor
      accounting for the increase in patient survival after second transplant.

PMID- 9763559
TI  - A Gln747-->Pro substitution in the IIb subunit is responsible for a moderate
      IIbbeta3 deficiency in Glanzmann thrombasthenia.
AB  - To clarify a molecular defect responsible for moderate alphaIIb beta3 deficiency,
      we examined two unrelated patients, MT and MS, suffering from type II and type I
      Glanzmann thrombasthenia (GT), respectively. Sequence analysis of polymerase
      chain reaction (PCR) fragments derived from platelet mRNA showed a single A-->C
      substitution at nucleotide (nt) 2334 leading to a Gln747--> Pro in alphaIIb in
      both patients. Allele-specific restriction enzyme analysis (ASRA) of genomic DNA
      demonstrated that patient MT was homozygous for the Gln747-->Pro substitution and
      patient MS was compound heterozygous for this substitution and for an RNA splice
      mutation at the consensus sequence of the splice acceptor site of exon 18 (AG-
      >AA). Furthermore, ASRA showed that, among 17 unrelated Japanese GT patients,
      this Gln747-->Pro substitution was detected in 4 patients, including MT and MS
      (homozygous, 2 patients; heterozygous, 2 patients). Cotransfection of
      Pro747alphaIIb and beta3 constructs into 293 cells resulted in moderate reduction
      in the amount of alphaIIb beta3 within the transfected cells as well as on the
      cell surface. However, Pro747alphaIIb beta3 bound the ligand mimetic monoclonal
      antibody (MoAb) PAC-1 after activation of alphaIIb beta3 by the MoAb PT25-2,
      suggesting that the mutant alphaIIb beta3 possesses the ligand-binding function.
      The association between the mutant proalphaIIb and beta3 was not disturbed.
      Surface labeling and pulse chase study showed that the Gln747-->Pro substitution
      moderately impaired both intracellular transport of the alphaIIb beta3
      heterodimers to the Golgi apparatus and endoproteolytic cleavage of proalphaIIb
      into heavy and light chains. By contrast, replacement of Gln747 with Ala by
      mutagenesis did not impair alphaIIbbeta3 expression on the cell surface. These
      results suggest that the presence of Pro, rather than the absence of Gln, at
      amino acid residue 747 on alphaIIb is responsible for moderate alphaIIbbeta3
      deficiency.

PMID- 9763560
TI  - Lipopolysaccharide induces the antiapoptotic molecules, A1 and A20, in
      microvascular endothelial cells.
AB  - The effect of lipopolysaccharide (LPS) on endothelial cells is a key component of
      the inflammatory response seen in Gram-negative sepsis. LPS does not cause death
      of cultured human endothelial cells. However, when the expression of new proteins
      is inhibited by cycloheximide, microvascular endothelial cells in culture undergo
      apoptosis. This finding suggests that LPS induces apoptotic and antiapoptotic
      pathways, with the antiapoptotic response being dependent on the synthesis of new
      proteins. Concurrent activation of apoptotic and antiapoptotic pathways has
      previously been documented for tumor necrosis factor (TNF). In the case of TNF,
      the antiapoptotic signal has been attributed to at least two cytoprotective
      proteins: the Bcl-2 homologue, A1, and the zinc-finger protein, A20. In this
      study, we demonstrate that both these molecules are induced in microvascular
      endothelial cells by LPS. Enforced overexpression of either A1 or A20 inhibits
      LPS and cycloheximide-initiated apoptosis. Induction of A1 and A20 does not
      require synthesis of intermediary proteins, but is dependent on the presence of
      soluble CD14. In addition, we show that inhibition of signaling by the
      transcription factor, NF-kappaB, blocks accumulation of A1 and A20 mRNA. Taken
      together, our findings suggest that LPS directly induces expression of the
      cytoprotective proteins, A1 and A20, via a CD14-dependent pathway requiring
      activation of NF-kappaB.

PMID- 9763561
TI  - The Val34Leu polymorphism in the A subunit of coagulation factor XIII contributes
      to the large normal range in activity and demonstrates that the activation
      peptide plays a role in catalytic activity.
AB  - There is a wide normal range of coagulation factor XIII activity that has never
      been adequately explained. A polymorphism substituting leucine for valine at
      position 34 in the activation peptide of the A subunit of factor XIII has
      recently been discovered in nondeficient individuals, and the present studies
      indicate that the leucine substitution results in a significant increase in
      transglutaminase activity. The frequency of the Leu34 allele in the Australian
      Caucasian population is 0.27, which is high enough to suggest that the
      inheritance of either the Val34 or Leu34 alleles may contribute to the wide
      normal range of activity. Although there has been structural evidence indicating
      that the activation peptide does not dissociate from the enzyme after thrombin
      cleavage, the discovery of elevated activity resulting from the Leu34
      substitution is the first direct evidence that the activation peptide plays a
      continuing role in the function of factor XIII.

PMID- 9763562
TI  - Polymorphisms of platelet membrane glycoprotein Ib associated with arterial
      thrombotic disease.
AB  - Platelet membrane glycoprotein Ibalpha (GPIbalpha) is a major receptor for von
      Willebrand factor and thrombin, which plays a key role in the initial development
      of thrombi. Two polymorphisms (HPA-2 and VNTR) that affect phenotype have been
      described in GPIbalpha. The relevance of these polymorphisms to thrombotic
      disease was investigated by genotypic identification in three case-control
      studies: 104 case patients with acute cerebrovascular disease (CVD), 101 case
      patients with acute coronary heart disease (CHD), 95 patients with deep venous
      thrombosis (DVT), and one control age-, sex-, and race-matched for each case
      patient. Results show that the C/B genotype of the VNTR and the HPA-2b
      polymorphisms of GPIbalpha are strongly associated with increased risk of
      coronary heart disease and cerebral vascular disease but not with deep vein
      thrombosis. These two polymorphisms of GPIbalpha may represent newly identified
      risk factors for arterial thrombotic disease, but not for venous thrombosis.

PMID- 9763563
TI  - Human integrin beta3 gene expression: evidence for a megakaryocytic cell-specific
      cis-acting element.
AB  - The human integrin beta3 participates in a wide range of adhesive biologic
      functions and is expressed in a selected subset of tissues, but little is known
      about the cis-acting DNA elements or trans-acting factors responsible for this
      regulation. Using cell lines characterized for beta3 expression, a number of
      upstream regulatory regions in the beta3 gene were identified. (1) The three
      regions from -1159 to -584, -290 to -146, and -126 to -115 demonstrated positive,
      negative, and negative activity, respectively. (2) The region from -115 to +29 of
      the beta3 gene was sufficient for cell-specific activity. Deletion of the
      sequence from -115 to -89 produced a 6- to 40-fold reduction in reporter gene
      activity in beta3-expressing megakaryocytic cell lines (K562, Dami, and HEL), but
      only a 1.7- and 2.7-fold reduction, respectively, in beta3-expressing endothelial
      and melanoma cell lines, and 1.3- and 2. 8-fold reduction, respectively, in non
      beta3-expressing Chinese hamster ovary and 293 cell lines. This sequence also
      bound nuclear proteins in a cell-specific manner in electrophoretic mobility
      shift assays. Mutational analysis indicated that the sequence GAGGGG (positions 
      113 to -108) is a megakaryocytic cell line-specific cis-acting element. (3) The
      region from -89 to +29 promoted lower activity in all cell lines. We also provide
      evidence that a CCCACCC sequence at position -70 has transcriptional activity,
      most likely through the Sp1 transcription factor. These data supply the first
      detailed map of the transcriptional regulatory elements of the 5' region of the
      beta3 gene, define positive regulatory sequences with potent megakaryocyte
      preferential activity, and indicate that the ubiquitous transcription factor,
      Sp1, may augment beta3 gene expression.

PMID- 9763564
TI  - Tissue distribution and regulation of murine von Willebrand factor gene
      expression in vivo.
AB  - von Willebrand factor (vWF) is frequently used as a biochemical marker for
      endothelial cells (ECs). Despite this, little is known about the relative level
      of expression and regulation of this hemostatic factor in ECs in different
      vascular beds in vivo. In the present study, we used quantitative reverse
      transcription polymerase chain reaction and in situ hybridization analysis to
      study vWF gene expression in murine tissues. Large differences in the level of
      vWF mRNA were observed when comparing highly vascularized tissues, with the lung
      and brain containing 5 to 50 times higher concentrations of vWF mRNA than the
      kidney and liver. In this regard, ECs of small vessels and some microvessels in
      the lung and brain expressed abundant vWF mRNA, whereas ECs of similar sized
      vessels in the liver and kidney expressed relatively low levels. In general,
      significantly higher levels of vWF mRNA and antigen were demonstrated in ECs of
      larger vessels compared with microvessels and in venous ECs compared with
      arterial ECs. Although intraperitoneal administration of endotoxin (or tumor
      necrosis factor-alpha) increased plasma vWF levels, it had variable effects on
      the steady-state level of vWF mRNA in murine tissues (ie, it decreased vWF mRNA
      in many tissues, increased it in others, and had little effect on still others).
      These results indicate that vWF is differentially expressed and regulated in ECs
      present in different tissues and within the same vascular bed.

PMID- 9763565
TI  - Ig heavy chain third complementarity determining regions (H CDR3s) after stem
      cell transplantation do not resemble the developing human fetal H CDR3s in size
      distribution and Ig gene utilization.
AB  - Previous studies have suggested that the B-cell repertoire after stem cell
      transplantation resembles the developing repertoire in the fetus. Fetal and adult
      repertoires differ strikingly at the molecular level in Ig heavy chain third
      complementarity determining region (H CDR3) size distribution and Ig gene
      utilization. Previously, the posttransplant repertoire has not been studied fully
      in this regard. In this study, we analyzed H CDR3s posttransplant using CDR3
      fingerprinting, single-strand conformation polymorphism (SSCP), and random
      sequencing. Eleven adult patients who received either autologous (n = 6) or
      allogeneic adult sibling (n = 5) hematopoietic stem cell transplants were
      studied. IgM H CDR3 repertoires demonstrated limited clonal diversity within the
      first 6 to 10 weeks posttransplant. By 3 to 4 months, the IgM H CDR3 repertoires
      were as diverse as those in healthy adults. Reconstitution of the IgM diversity
      correlated with the expansion of the multimember VH3 family. By contrast, the
      contribution of the single-member VH6 family was limited in most patients up to 6
      to 9 months. No evidence was seen for greater contribution of VH6 posttransplant.
      IgG repertoires remained clonally restricted at all times. In all patients, H
      CDR3 sizes fell within adult limits. Direct nucleotide sequencing of H CDR3s
      showed adult-type N-nucleotide insertions and Ig gene utilization. These results
      indicate that the emerging repertoire posttransplant does not resemble the
      developing fetal repertoire at the molecular level.

PMID- 9763566
TI  - RP105 is associated with MD-1 and transmits an activation signal in human B
      cells.
AB  - RP105 was originally discovered as a mouse B-cell surface molecule that transmits
      an activation signal. The signal leads to resistance against irradiation-induced
      apoptosis and massive B-cell proliferation. Recently, we found that mouse RP105
      is associated with another molecule, MD-1. We have isolated here the human MD-1
      cDNA. We show that human MD-1 is also associated with human RP105 and has an
      important role in cell surface expression of RP105. We also describe a monoclonal
      antibody (MoAb) that recognizes human RP105. Expression of RP105 is restricted to
      CD19(+) B cells. Histological studies showed that RP105 is expressed mainly on
      mature B cells in mantle zones. Germinal center cells are either dull or
      negative. RP105 is thus a novel human B-cell marker that is preferentially
      expressed on mature B cells. Moreover, the anti-RP105 MoAb activates B cells,
      leading to increases in cell size, expression of a costimulatory molecule CD80,
      and DNA synthesis. The B-cell activation pathway using RP105 is conserved in
      humans.

PMID- 9763567
TI  - A regulatory role for Fcgamma receptors CD16 and CD32 in the development of
      murine B cells.
AB  - Early in development, murine B-lineage progenitor cells express two classes of
      IgG Fc receptors (FcgammaR) designated as FcgammaRII (CD32) and FcgammaRIII
      (CD16), but mature B lymphocytes only express FcgammaRII (CD32), which functions
      as an inhibitor of B-cell activation when it is induced to associate with mIgM.
      The functions of CD16 and CD32 on B-lineage precursor cells have not previously
      been investigated. To search for FcgammaR functions on developing B-lineage
      cells, normal murine bone marrow cells were cultured in the presence of 2.4G2, a
      rat monoclonal antibody that binds to CD16 and CD32, or in the presence of
      control normal rat IgG, and then the B-lineage compartment was analyzed for
      effects. Cultures that contained 2.4G2 showed enhanced growth and differentiation
      of B-lineage cells compared with control cultures. The enhancing effect of 2.4G2
      also occurred when fluorescence-activated cell-sorted B-cell precursors (B220(+),
      sIgM-, HSAhigh, FcgammaR+) from normal bone marrow were cocultured with BMS2, a
      bone marrow stromal cell line, but not when they were cultured in BMS2
      conditioned media. The enhancement of B-lineage development induced by 2.4G2 was
      CD16-dependent and CD32-dependent, because 2.4G2 did not effect B-lineage growth
      or differentiation in cultures of bone marrow from mice in which either the gene
      encoding CD16 or CD32 had been disrupted. Analysis of fresh bone marrow from the
      CD16 gene-disrupted mice showed normal numbers and distribution of cells within
      the B-cell compartment, but in CD32 gene-disrupted mice, the B-cell compartment
      was significantly enlarged. These experiments provide several lines of evidence
      that the FcgammaR expressed on murine B-cell precursors can influence their
      growth and differentiation.

PMID- 9763568
TI  - Prolonged phenotypic, functional, and molecular change in group I Burkitt
      lymphoma cells on short-term exposure to CD40 ligand.
AB  - Group I Burkitt lymphoma (BL) cell lines (L3055, Elijah, Louckes, BL2, and BL29)
      retaining the original biopsy phenotype were found to undergo prolonged
      phenotypic, functional, and molecular change on short-term exposure to soluble
      recombinant CD40L trimer. Sensitivity to, extent of, and duration of change
      appeared to reflect passage number in that the earliest passaged lines, L3055 and
      BL29, were generally the most susceptible. Culture of group I BL lines with CD40L
      resulted in significant growth arrest (without apoptosis) that, for L3055 cells,
      was sustained for 7 to 9 days after 72 hours of exposure. This was accompanied by
      the formation of large homotypic aggregates together with gross changes in
      individual cell morphology and a concomitant upregulation of CD54 (ICAM-1). Three
      of the five group I BL lines exhibited rapid downregulation of the hallmark CD77
      surface antigen, which, for L3055 cells, was maintained for at least 12 days
      after 72 hours of incubation with CD40L. With the exception of BL2, all group I
      BL lines were induced to express CD40 homodimers on CD40-stimulation, whereas
      only monomers were detected in unstimulated cells. Experiments using CD40
      transfected Rat-1 fibroblasts showed that the ability to signal for dimer
      formation required Thr234 of CD40. For L3055 and BL29 cells, an initial 72 hours
      of exposure to CD40L resulted in the maintenance of homodimers for up to 14 and
      10 days, respectively. There was a close correlation between the induction and
      duration of CD40 homodimers and the appearance of Bcl-2. For L3055 cells, which
      are sensitive to apoptosis-induction on BCR-engagement, exposure to CD40L for 72
      hours was found to provide considerable protection from anti-IgM, which was still
      significant to 20 days. The implications of such sustained effects on relatively
      short-term exposure of tumor B cells to CD40L are discussed.

PMID- 9763569
TI  - A high frequency of circulating B cells share clonotypic Ig heavy-chain VDJ
      rearrangements with autologous bone marrow plasma cells in multiple myeloma, as
      measured by single-cell and in situ reverse transcriptase-polymerase chain
      reaction.
AB  - In multiple myeloma (MM), the VDJ rearrangement of the immunoglobulin heavy chain
      expressed by MM plasma cells provides a unique clonotypic marker. Although
      clonotypic MM cells have been found in the circulation, their number has been
      controversial. Our objective was to provide direct evidence, using single-cell
      assays, for the frequency of clonotypic cells in blood of 18 MM patients, and to
      confirm their identity as B cells. The clonotypic Ig heavy-chain (IgH) VDJ was
      determined from single plasma cells using consensus reverse transcriptase
      polymerase chain reaction (RT-PCR), subcloning, and sequencing. For all patients,
      using patient-specific primers, clonotypic transcripts were amplified from 10 or
      more individual plasma cells. Using in situ RT-PCR, for all patients greater than
      80% of plasma cells were found to be clonotypic. Three separate methods, RT-PCR,
      single-cell RT-PCR, and in situ RT-PCR, were used to analyze clonotypic cells in
      peripheral blood mononuclear cells (PBMC) from MM patients. Sequencing of the IgH
      transcripts expressed by individual cells obtained by limiting dilution of
      freshly isolated PBMC from a MM patient showed that all B cells expressed an
      identical CDR3. This intraclonal homogeneity indicates an escape from antigenic
      selection, characteristic of malignant B cells. For this patient, the frequency
      of clonotypic PBMC, about 25%, was comparable to the number of PBMC B cells
      (34%). Because the PBMC included less than 1% plasma cells, virtually all
      clonotypic PBMC must be B cells. Using single-cell RT-PCR, clonotypic IgH
      transcripts were identified in individual sorted B cells from blood. To
      accurately quantify the number of clonotypic B cells, sorted B cells derived from
      18 MM patients (36 samples) and 18 healthy donors (53 samples) were analyzed
      using in situ RT-PCR with patient-specific primers. Clonotypic transcripts were
      not detectable among normal B cells. For the 18 MM patients, a mean of 66% +/- 4%
      (SE) of blood B cells were clonotypic (range, 9% to 95%), with mean absolute
      number of 0.15 +/- .02 x 10(9)/L blood. Over time in individual patients,
      conventional chemotherapy transiently decreased circulating clonotypic B cells.
      Their numbers were increased in granulocyte colony-stimulating factor (G-CSF)-
      mobilized blood of one patient. However, clonotypic B cells of a one patient
      became undetectable after allogeneic transplant, correlating with complete
      remission. Although contributions to MM spread and progression is likely, their
      malignant status and impact has yet to be clarified. Their high frequency in the
      blood, and their resistence to conventional chemotherapy suggests that the number
      of circulating clonotypic cells should be clinically monitored, and that
      therapeutic targeting of these B cells may benefit myeloma patients.

PMID- 9763570
TI  - The relationship between thiopurine methyltransferase activity and genotype in
      blasts from patients with acute leukemia.
AB  - The level of expression of the enzyme thiopurine methyltransferase (TPMT) is an
      important determinant of the metabolism of thiopurines used in the treatment of
      acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Studies in
      red blood cells (RBC) have shown that TPMT expression displays genetic
      polymorphism with 11% of individuals having intermediate and one in 300
      undetectable levels. The genetic basis for this polymorphism has now been
      elucidated and polymerase chain reaction (PCR)-based assays described for the
      most common mutations accounting for reduced activity. In previous studies,
      genotype has been correlated with red blood cell activity. In this report, we
      describe the relationship between genotype and TPMT activity measured directly in
      the target of drug action, the leukemic cell. We have demonstrated that the TPMT
      activity in lymphoblasts from 38 children and adults found by PCR to be
      homozygotes (*1/*1) was significantly higher than that in the five heterozygotes
      (*1/*3) detected (median, 0.25 v 0.08, P < .002, Mann-Whitney U). Similar results
      were obtained when results from children were analyzed separately. However,
      comparison of activity in blasts from AML and ALL showed a higher level in the
      former (0.35 v 0.22 nU/mg, P < .002, n = 17, 35), suggesting that factors other
      than genotype may also influence expression.

PMID- 9763571
TI  - Altered expression and activity of topoisomerases during all-trans retinoic acid
      induced differentiation of HL-60 cells.
AB  - Regulation of topoisomerase II (TOPO II) isozymes alpha and beta is influenced by
      the growth and transformation state of cells. Using HL-60 cells induced to
      differentiate by all-trans retinoic acid (RA), we have investigated the
      expression and regulation of TOPO II isozymes as well as the levels of
      topoisomerase I (TOPO I). During RA-induced differentiation of human leukemia HL
      60 cells, levels of TOPO I remained unchanged, whereas the levels and
      phosphorylation of TOPO IIalpha and TOPO IIbeta proteins were increased twofold
      to fourfold and fourfold to eightfold, respectively. The elevation of TOPO II
      (alpha and beta) protein levels and phosphorylation was apparent at 48 hours of
      treatment with RA and persisted through 96 hours. The increased level of TOPO
      IIbeta protein was also detected in differentiated cells subsequently cultured
      for 96 hours in RA-free medium. Pulse chase experiments in cells labeled with 35S
      methionine showed that the rate of degradation of TOPO IIbeta protein in control
      cells was about twofold faster than that in the differentiated RA-treated cells.
      The level of decatenation activity of kDNA was comparable in nuclear extracts
      from control or RA-treated cells. Whereas etoposide (1 to 10 micromol/L) -induced
      DNA cleavage was not significantly different, apoptosis was significantly lower
      (P = .012) in RA-treated versus control cells after exposure to 10 micromol/L
      etoposide. Consistent with unaltered levels of TOPO I, camptothecin (CPT) 
      induced DNA cleavage was similar in control or RA-treated cells. However,
      apoptosis after exposure to 1 to 10 micromol/L CPT was significantly lower (P =
      .003 to P < .001) in RA-treated versus control cells. Results suggest that TOPO
      IIbeta protein levels are posttranscriptionally regulated and that degradation of
      TOPO IIbeta is decreased during RA-induced differentiation. Furthermore, whereas
      the total level of TOPO II (alpha + beta) is increased with RA, the level of TOPO
      II catalytic activity and etoposide-stabilized DNA cleavage activity remains
      unaltered. Thus, TOPO IIbeta may have a specific role in transcription of genes
      involved in differentiation with RA treatment.

PMID- 9763572
TI  - DNA fiber fluorescence in situ hybridization analysis of immunoglobulin class
      switching in B-cell neoplasia: aberrant CH gene rearrangements in follicle center
      cell lymphoma.
AB  - Immunoglobulin class switching usually involves deletion of part of the
      immunoglobulin CH region. By DNA fiber fluorescence in situ hybridization (FISH)
      with a barcode of probes covering the DH, JH, and CH genes, the configuration of
      the entire CH region can be visualized on single DNA molecules. Using this
      technique, we have studied class switching in three types of B-cell neoplasia,
      mantle-cell lymphoma (MCL), follicular lymphoma (FL) and hairy cell leukemia
      (HCL), representing B cells in, respectively, pregerminal center, germinal
      center, and postgerminal center stages of development. In MCL and FL,
      simultaneous detection of the t(11;14) and t(14;18) breakpoint with probes for
      the BCL-1 and BCL-2 loci, respectively, allowed differentiation between
      productive and nonproductive alleles. In none of 10 MCL cases was class switching
      detected. In 21 HCL, all nonimmunoglobulin M (IgM) cases had class-switch
      deletion consistent with the expressed isotype on at least one allele. In FL,
      however, a peculiar pattern of CH rearrangement was observed. In IgM expressing
      FL, the translocated alleles had switched in 11 of 13 cases, and the
      nontranslocated allele showed complex rearrangements downstream from the Cmu
      Cdelta genes in 9 of 13 cases. These downstream rearrangements may reflect tumor
      specific deregulation of the class-switch machinery. All seven immunoglobulin G
      (IgG) expressing FL showed class switching on both alleles. Fiber FISH analysis
      also showed several polymorphisms. The most frequent one, present on 38% of all
      analyzed alleles, consisted of an extra Cgamma gene or pseudogene in the 3'
      cluster.

PMID- 9763573
TI  - CBFA2(AML1) translocations with novel partner chromosomes in myeloid leukemias:
      association with prior therapy.
AB  - CBFA2(AML1) has emerged as a gene critical in hematopoiesis; its protein product
      forms the DNA-binding subunit of the heterodimeric core-binding factor (CBF) that
      binds to the transcriptional regulatory regions of genes, some of which are
      active specifically in hematopoiesis. CBFA2 forms a fusion gene with ETO and
      MDS1/EVI1 in translocations in myeloid leukemia and with ETV6(TEL) in the
      t(12;21) common in childhood pre-B acute lymphoblastic leukemia. We have analyzed
      samples from 30 leukemia patients who had chromosome rearrangements involving
      21q22 by using fluorescence in situ hybridization (FISH). Our analysis showed
      that 7 of them involved CBFA2 and new translocation partners. Two patients had a
      t(17;21)(q11.2;q22), whereas the other 5 had translocations involving 1p36, 5q13,
      12q24, 14q22, or 15q22. Five of these novel breakpoints in CBFA2 occurred in
      intron 6; this same intron is involved in the t(3;21). One breakpoint mapped to
      the t(8;21) breakpoint region in intron 5, and 1 mapped 5' to that region. All 7
      CBFA2 rearrangements resulted from balanced translocations. All 7 patients had
      myeloid disorders (acute myeloid leukemia or myelodysplastic syndrome); 2 were de
      novo and 5 had treatment histories that included topoisomerase II targeting
      agents. The association of therapy-related disorders with translocations
      involving CBFA2 was significant by Fisher's exact test (P < .003). These results
      provide further evidence that this region of CBFA2 is susceptible to breakage in
      cells exposed to topoisomerase II inhibitors.

PMID- 9763574
TI  - Fluorescence in situ hybridization of progenitor cells obtained by fluorescence
      activated cell sorting for the detection of cells affected by chromosome
      abnormality trisomy 8 in patients with myelodysplastic syndromes.
AB  - Myelodysplastic syndrome (MDS) is believed to be a stem-cell disorder involving
      cytopenia and dysplastic changes in three hematopoietic lineages. However, the
      involvement of pluripotent stem cells and progenitor cells has not been clarified
      conclusively. To address this issue, we used fluorescence in situ hybridization
      (FISH) of blood and bone marrow (BM) smears for mature cells and FISH of cells
      sorted by fluorescence-activated cell sorting for progenitor cells. Seven
      patients with MDS associated with trisomy 8 were studied. FISH showed +8 in
      granulocytes, monocytes, and erythroblasts, but not in lymphocytes. Sorted cells
      of T (CD3(+)), B (CD19(+)), and NK cells (CD3(-)CD56(+)) from peripheral blood
      did not contain +8, nor did CD34(+) subpopulations from BM including B
      (CD34(+)CD19(+)), T/NK (CD34(+)CD7(+)) progenitors, and pluripotent stem cells
      (CD34(+)Thy1(+)). The +8 chromosome abnormality was identified in stem cells only
      at the level of colony-forming unit of granulocyte-erythrocyte-macrophage
      megakaryocyte (CFU-GEMM; CD34(+)CD33(+)). It may thus be concluded that cells
      affected by trisomy 8 in the context of MDS are at the CFU-GEMM level and that
      cells of lymphoid lineage are not involved. These results provide new insights
      into the biology of MDS and suggest that intensive chemotherapy and autologous BM
      transplantation may become important therapeutic strategies.

PMID- 9763575
TI  - 8Cl-cAMP cytotoxicity in both steroid sensitive and insensitive multiple myeloma
      cell lines is mediated by 8Cl-adenosine.
AB  - We have examined the cytotoxic effects of cyclic adenosine-3', 5'-monophosphate
      (cAMP) derivatives on multiple myeloma cells lines and determined that the 8
      Chloro substituted derivative (8Cl-cAMP) is one of the most potent. We report
      here that 8Cl-cAMP is cytotoxic to both steroid sensitive and insensitive myeloma
      cells with a half maximal concentration of approximately 3 micromol/L. 8Cl-cAMP
      toxicity in myeloma cells is dependent on phosphodiesterase activity in the serum
      of cell culture medium. A metabolite of 8Cl-cAMP, 8-Chloro-adenosine (8Cl-AD),
      kills myeloma cells as effectively as 8Cl-cAMP. Adenosine deaminase (ADA)
      converts 8Cl-AD into 8Cl-inosine and abrogates the cytotoxic effects of 8Cl-cAMP,
      8Cl-AMP, and 8Cl-AD, as does 5-(p-Nitrobenzyl)-6-Thio-Inosine (NBTI), an
      inhibitor of nucleoside uptake. These data suggest that 8Cl-cAMP must be
      converted to 8Cl-AD and that 8Cl-AD is the compound that enters the cell.
      Contrary to glucocorticoid-mediated cell death in myeloma cells, the pathway of
      8Cl-AD-mediated cell death appears to be independent of interleukin-6 (IL-6)
      actions. Although the exact mode of action for this agent is currently unknown,
      its ability to kill steroid sensitive and insensitive multiple myeloma cells in
      an IL-6 independent fashion may offer exciting new therapeutic options.

PMID- 9763576
TI  - Detection of clonal Hodgkin and Reed-Sternberg cells with identical somatically
      mutated and rearranged VH genes in different biopsies in relapsed Hodgkin's
      disease.
AB  - Hodgkin's disease (HD) represents a malignant lymphoma in which the putative
      malignant Hodgkin and Reed-Sternberg (H-RS) cells are rare and surrounded by
      abundant reactive cells. Single-cell analyses showed that H-RS cells regularly
      bear clonal Ig gene rearrangements. However, there is little information on the
      clinical evolution of HD in a given patient. In this study, we used the single
      cell polymerase chain reaction (PCR) to identify H-RS cells with clonal Ig gene
      rearrangements in biopsy specimens of patients with relapsed HD. The obtained
      clonal variable region heavy-chain (VH) gene rearrangements were used to
      construct tumor-clone-specific oligonucleotides spanning the complementarity
      determining region (CDR) III and somatically mutated areas in the rearranged VH
      gene. A number of biopsies were obtained during a period of 3 years from two HD
      patients. H-RS cells with identical VH rearrangements were detected in two
      separate infiltrated lymph nodes from one patient with nodular sclerosis HD. In a
      second patient with mixed cellularity HD subtype, clonal VH rearrangements with
      identical sequences were detected in infiltrated spleen and two lymph node
      biopsies. Despite the high sensitivity of the PCR method used (one clonal cell in
      10(5) mononuclear cells), residual H-RS cells were not found in peripheral blood,
      leukapheresis material, purified CD34(+) stem cells or bone marrow. The results
      show that different specimens from relapsed patients suffering from classical HD
      carry the same clonotypic IgH rearrangements with identical somatic mutations,
      demonstrating the persistence and the dissemination of a clonal tumor cell
      population. Thus, PCR assays with CDRIII-specific probes derived from clonal H-RS
      cells are of clinical importance in monitoring the dissemination of HD and tumor
      progression and could be useful for analysis of minimal residual disease after
      autologous stem cell transplantation.

PMID- 9763577
TI  - Primary myeloma cells growing in SCID-hu mice: a model for studying the biology
      and treatment of myeloma and its manifestations.
AB  - Progress in unraveling the biology of myeloma has suffered from lack of an in
      vitro or in vivo system for reproducible growth of myeloma cells and development
      of disease manifestations. The SCID-hu mouse harbors a human microenvironment in
      the form of human fetal bone. Myeloma cells from the bone marrow of 80% of
      patients readily grew in the human environment of SCID-hu mice. Engraftment of
      myeloma cells was followed by detectable human Ig levels in the murine blood.
      Myeloma-bearing mice had high levels of monotypic human Igs, high blood calcium
      levels, increased osteoclast activity, and severe resorption of the human bones.
      The human microenvironment was infiltrated with Epstein-Barr virus-negative
      monoclonal myeloma cells of the same clonality as the original myeloma cells.
      Active angiogenesis was apparent in areas of myeloma cell infiltration; the new
      endothelial cells were of human origin. We conclude that the SCID-hu mouse is a
      favorable host for studying the biology and therapy of myeloma and that a normal
      bone marrow environment can support the growth of myeloma cells.

PMID- 9763578
TI  - Fas/APO-1 (CD95)-mediated apoptosis is activated by interferon-gamma and
      interferon- in interleukin-6 (IL-6)-dependent and IL-6-independent multiple
      myeloma cell lines.
AB  - A poor response to Fas-induced apoptosis is evident in some multiple myeloma (MM)
      cell lines and primary cells. In this study, we have examined the possibility to
      increase the sensitivity to Fas-induced apoptosis by pretreatment of MM cells
      with interferon-gamma (IFN-gamma) or interferon-alpha (IFN-alpha). Both IFN-gamma
      and IFN-alpha markedly increased the Fas-induced apoptosis in all cell lines
      tested (U-266-1970, U-266-1984, and U-1958). In the U-266-1970 and U-1958 cell
      lines, pretreatment with either IFN-gamma or IFN-alpha also inhibited
      proliferation in a dose-dependent manner. In contrast, IFN-gamma activation of
      the Fas death pathway in the U-266-1984 cells was not accompanied by growth
      inhibition. Incubation with the IFNs increased the Fas antigen expression in one
      of three cell lines but did not alter the expression of Bcl-2 or Bax. The IFNs
      are important regulators of growth and survival in MM cells. Our results suggest
      that activation of Fas-mediated apoptosis is a novel mechanism by which the IFNs
      exert inhibitory effects on MM cells.

PMID- 9763579
TI  - Alterations in protein-DNA interactions in the gamma-globin gene promoter in
      response to butyrate therapy.
AB  - The mechanisms by which pharmacologic agents stimulate gamma-globin gene
      expression in beta-globin disorders has not been fully established at the
      molecular level. In studies described here, nucleated erythroblasts were isolated
      from patients with beta-globin disorders before and with butyrate therapy, and
      globin biosynthesis, mRNA, and protein-DNA interactions were examined. Expression
      of gamma-globin mRNA increased twofold to sixfold above baseline with butyrate
      therapy in 7 of 8 patients studied. A 15% to 50% increase in gamma-globin protein
      synthetic levels above baseline gamma globin ratios and a relative decrease in
      beta-globin biosynthesis were observed in responsive patients. Extensive new in
      vivo footprints were detected in erythroblasts of responsive patients in four
      regions of the gamma-globin gene promoter, designated butyrate-response elements
      gamma 1-4 (BRE-G1-4). Electrophoretic mobility shift assays using BRE-G1
      sequences as a probe demonstrated that new binding of two erythroid-specific
      proteins and one ubiquitous protein, alphaCP2, occurred with treatment in the
      responsive patients and did not occur in the nonresponder. The BRE-G1 sequence
      conferred butyrate inducibility in reporter gene assays. These in vivo protein
      DNA interactions in human erythroblasts in which gamma-globin gene expression is
      being altered strongly suggest that nuclear protein binding, including alphaCP2,
      to the BRE-G1 region of the gamma-globin gene promoter mediates butyrate activity
      on gamma-globin gene expression.

PMID- 9763580
TI  - Serum transferrin receptor and transferrin receptor-ferritin index identify
      healthy subjects with subclinical iron deficits.
AB  - Despite the established utility of serum transferrin receptor (sTfR), serum
      ferritin, and the sTfR/log ferritin ratio (TfR-F Index) in the diagnosis of iron
      deficiency (ID) anemia, the numeric values of these parameters, which are
      indicative of subclinical ID, remain to be clearly defined. In this study, 65
      apparently healthy nonanemic adults (22 men and 43 women) were treated with 3
      months of oral iron supplementation to evaluate its effect on parameters
      reflecting iron status and to determine the prevalence of subclinical iron
      deficiency in apparently healthy adults. Significant supplementation-induced
      changes were observed in sTfR, ferritin, and TfR-F Index values in women, whereas
      in men, none of the studied parameters showed any significant change. Iron
      deficient erythropoiesis (IDE) was not observed in men, but was found in 17 women
      (40%). Although individuals with a compromised iron status may be represented in
      substantial numbers in conventional reference populations, they can be readily
      identified using sTfR, ferritin, and TfR-F Index determinations.

PMID- 9763582
TI  - Sickle cell adhesion to laminin: potential role for the alpha5 chain.
AB  - Sickle red blood cell (RBC) adhesion to the endothelium and to exposed,
      underlying subendothelial proteins is believed to contribute to vascular
      occlusion in sickle cell disease. Laminin, a major component of the
      subendothelium, supports significant adhesion of sickle, but not normal RBCs. The
      purpose of this study was to define the adhesive region for sickle RBCs within a
      human laminin preparation using a flow adhesion assay designed to mimic
      physiologic flow through postcapillary venules. Because sickle RBCs did not
      adhere to the common laminin contaminants entactin or collagen type IV, neither
      of these proteins are likely to contribute to the observed adhesion to laminin.
      Known adhesive regions of laminin neither supported nor inhibited sickle RBC
      adhesion to laminin, suggesting a mechanism of adhesion previously
      uncharacterized in other laminin adhesion studies. Moreover, sickle RBCs did not
      adhere to mouse EHS laminin or to human laminin-2 (merosin), eliminating the
      alpha1, alpha2, beta1, and gamma1 chains as mediators of sickle cell adhesion.
      The monoclonal antibody 4C7, which binds at or near the G-domain of the laminin
      alpha5 chain, significantly inhibited sickle RBC adhesion. These results suggest
      that an adhesive region for sickle RBCs is contained within the laminin alpha5
      chain.

PMID- 9763581
TI  - Molecular identification and functional characterization of a novel protein that
      mediates the attachment of erythroblasts to macrophages.
AB  - We have previously identified a novel protein that mediates the attachment of
      erythroblasts to macrophages in vitro. This attachment promotes terminal
      maturation and enucleation of erythroblasts (Hanspal and Hanspal, Blood 84:3494,
      1994). This protein is referred to here as Emp for erythroblast macrophage
      protein. Two immunologically related isoforms of Emp with apparent molecular
      weights of 33 kD and 36 kD were detected in macrophage membranes. The complete
      amino acid sequence of the larger isoform of Emp was deduced from the nucleotide
      sequence of a full-length 2.0-kb cDNA that was isolated from a human macrophage
      cDNA library using affinity-purified anti-Emp antibodies. Of the 2,005 bp, 1,185
      bp encode for 395 amino acids representing 43 kD (the sodium dodecyl sulfate
      polyacrylamide gel electrophoresis [SDS-PAGE] molecular mass is 36 kD). Northern
      blot analysis of human macrophage poly(A) RNA detected a message for Emp of 2.1
      kb. The deduced amino acid sequence contains a putative transmembrane domain near
      the N-terminus. To investigate the structure/function relationships of Emp,
      recombinant fusion proteins of full-length and truncated Emp were produced in
      bacteria, COS-7, and HeLa cells. Cell binding assays showed that the N-terminus
      is exposed on the cell surface. The recombinant Emp functions as a cell
      attachment molecule when expressed in heterologous cells. Furthermore, we showed
      that the demise of erythroblasts in the absence of Emp-mediated erythroblast
      macrophage association is accompanied by apoptosis. We postulate that Emp
      mediated contact between erythroblasts and macrophages promotes terminal
      maturation of erythroid cells by suppressing apoptosis.

PMID- 9763584
TI  - Role of CD28 in acute graft-versus-host disease.
AB  - Because CD28-mediated T-cell costimulation has a pivotal role in the initiation
      and maintenance of T-cell responses, we tested the hypothesis that CD28 is
      critical for the development of graft-versus-host disease (GVHD). We compared the
      in vivo effects of CD28(-/-) T cells transplanted from B6 donor with the CD28
      gene deleted by homologous recombination with those of CD28(+/+) T cells
      transplanted from wild-type C57BL/6 (B6) donor. Fifty million CD28(-/-) or
      CD28(+/+) splenocytes from B6 mice were transplanted into unirradiated (B6 x
      DBA/2)F1 (BDF1) recipients. Unlike CD28(+/+), CD28(-/-) T cells from B6 mice had
      lower levels of proliferation and interleukin-2 production, had a limited ability
      to generate cytotoxic T lymphocytes against the recipient, and did not induce
      immune deficiency, despite survival in the recipient for at least 28 days. The
      ability to prevent rejection was reduced by the absence of CD28, because as many
      as 1.0 x 10(7) CD28(-/-) CD8(+) cells were needed to prevent rejection of major
      histocompatibility complex (MHC) class-I incompatible marrow in sublethally
      irradiated (550 cGy) bm1 recipients, whereas 8.0 x 10(5) CD28(+/+) CD8(+) T cells
      were sufficient to produce a similar effect, indicating that CD28 on donor CD8(+)
      cells helps to eliminate host immunity. Two million CD4(+) CD28(-/-) or CD28(+/+)
      T cells were transplanted into sublethally irradiated (750 cGy), MHC class-II
      incompatible (B6 x bm12)F1 recipients. With CD28(-/-) cells, 44% of the
      recipients died at a median of 20 days compared with 94% at a median of 15 days
      with CD28(+/+) cells (P < .001). Two million CD8(+) CD28(-/-) or CD28(+/+) T
      cells were transplanted into sublethally irradiated (750 cGy), MHC class-I
      incompatible (B6 x bm1) F1 recipients. With CD28(-/-) cells, 25% of the
      recipients died at a median of 41 days compared with 100% at a median of 15 days
      with CD28(+/+) cells (P < . 001). (B6 x bm12)F1 and (B6 x bm1)F1 mice surviving
      after transplantation of CD28(-/-) cells recovered thymocytes, T cells, and B
      cells in numbers and function comparable with that of irradiation-control F1
      mice. We conclude that CD28 contributes to the pathogenesis and the severity of
      GVHD. Our results suggest that the severity of GVHD could be decreased by the
      administration of agents that block CD28 function in T lymphocytes.

PMID- 9763583
TI  - The relationship of the -5, -8, and -24 variant alleles in African Americans to
      triosephosphate isomerase (TPI) enzyme activity and to TPI deficiency.
AB  - In 424 African-American and 75 white subjects, we found that the -5 (TPI 592 A-
      >G), -8 (TPI 589 G-->A), and -24 (TPI 573 T-->G) variants in the triosephosphate
      isomerase (TPI) gene occurred frequently (41.0%) in the African-American subjects
      but did not occur in the whites. These data suggest that this set of
      polymorphisms may turn out to be one of the higher-incidence molecular markers of
      African lineage, a surprising finding because others had reported that these
      nucleotide substitutions were restricted to a small subset of African Americans
      who had been characterized as TPI-deficiency heterozygotes. Additionally, we
      investigated the relationship of these variants to TPI-enzyme activity. Although
      the variant substitutions (occurring in three haplotypes: -5 alone, -5 -8, and -5
      -8 -24) were associated with moderate reduction in enzyme activity, severe
      deficiency heterozygotes could not be identified with certainty, and none of the
      haplotypes were restricted to subjects with marked reduction of enzyme activity.
      Three subjects were homozygous for the -5 -8 haplotype, a finding inconsistent
      with the putative role of this haplotype as the cause of a null variant
      incompatible with life in homozygotes. Despite these findings, the possibility
      remains that the -5 -8 or -5 -8 -24 haplotypes may in some instances contribute
      to compound heterozygosity and clinical TPI deficiency.

PMID- 9763585
TI  - Catecholaminergic regulation of hematopoiesis in mice.

PMID- 9763586
TI  - Neural regulation of bone marrow.

PMID- 9763587
TI  - High risk of chronic graft-versus-host disease in unmanipulated allogeneic
      peripheral blood stem cell transplantation.

PMID- 9763588
TI  - Mechanical properties of stored red blood cells using optical tweezers.

PMID- 9763590
TI  - Juvenile genetic hemochromatosis is clinically and genetically distinct from the
      classical HLA-related disorder.

PMID- 9763589
TI  - A functional wild-type p53 gene is expressed in human acute myeloid leukemia cell
      lines.

PMID- 9763591
TI  - Hypermethylation of p15(INK4B) gene in a patient with acute myelogenous leukemia
      evolved from paroxysmal nocturnal hemoglobinuria.

PMID- 9763592
TI  - Interferon and ribavirin combination therapy in patients with chronic hepatitis C
      and mixed cryoglobulinemia.

PMID- 9763593
TI  - Questions raised by the Benelux CML Study Group: results from the randomized
      study with hydroxyurea alone versus hydroxyurea combined with low-dose interferon
      alpha2b for chronic myeloid leukemia.

PMID- 9763594
TI  - FGFR3 gene mutations associated with human skeletal disorders occur rarely in
      multiple myeloma.

PMID- 9763595
TI  - Interleukin-2 receptor subunit expression and function on human peripheral T
      cells is not dependent on the anticoagulant.

PMID- 9763596
TI  - Primary recurrent miscarriages: anti-beta2-glycoprotein I IgG antibodies induce
      an acquired activated protein C resistance that can be detected by the modified
      activated protein C resistance test.

PMID- 9763597
TI  - Antisense RNA crossing mitochondrial membrane?

PMID- 9763598
TI  - Magnetic resonance imaging in myelofibrosis.

PMID- 9763599
TI  - Detection of nonrandom chromosomal changes in multiple myeloma by comparative
      genomic hybridization.

PMID- 9763601
TI  - Immunocytochemical colocalization of specific immunoglobulin A with sendai virus
      protein in infected polarized epithelium.
AB  - Immunoglobulin (Ig)A provides the initial immune barrier to viruses at mucosal
      surfaces. Specific IgA interrupts viral replication in polarized epithelium
      during receptor-mediated transport, probably by binding to newly synthesized
      viral proteins. Here, we demonstrate by immunoelectron microscopy that specific
      IgA monoclonal antibodies (mAbs) accumulate within Sendai virus-infected
      polarized cell monolayers and colocalize with the hemagglutinin- neuraminidase
      (HN) viral protein in a novel intracellular structure. Neither IgG specific for
      HN nor irrelevant IgA mAbs colocalize with viral protein. Treatment of cultures
      with viral-specific IgA but not with viral-specific IgG or irrelevant IgA
      decreases viral titers. These observations provide definitive ultrastructural
      evidence of a subcellular compartment in which specific IgA and viral envelope
      proteins interact, further strengthening our hypothesis of intracellular
      neutralization of virus by specific IgA antibodies. Our results have important
      implications for intracellular protein trafficking, viral replication, and viral
      vaccine development.

PMID- 9763600
TI  - Adenosine diphosphate (ADP)-ribosylation of the guanosine triphosphatase (GTPase)
      rho in resting peripheral blood human T lymphocytes results in pseudopodial
      extension and the inhibition of T cell activation.
AB  - Scrape loading Clostridium botulinum C3 exoenzyme into primary peripheral blood
      human T lymphocytes (PB T cells) efficiently adenosine diphosphate (ADP)
      ribosylates and thus inactivates the guanosine triphosphatase (GTPase) Rho. Basal
      adhesion of PB T cells to the beta1 integrin substrate fibronectin (Fn) was not
      inhibited by inactivation of Rho, nor was upregulation of adhesion using phorbol
      myristate acetate (PMA; 10 ng/ml) or Mn++ (1 mM) affected. Whereas untreated PB T
      cells adherent to Fn remain spherical, C3-treated PB T cells extend F-actin
      containing pseudopodia. Inactivation of Rho delayed the kinetics of PMA-dependent
      PB T cell homotypic aggregation, a process involving integrin alphaLbeta2.
      Although C3 treatment of PB T cells did not prevent adhesion to the beta1
      integrin substrate Fn, it did inhibit beta1 integrin/CD3-mediated costimulation
      of proliferation. Analysis of intracellular cytokine production at the single
      cell level demonstrated that ADP-ribosylation of Rho inhibited beta1 integrin/
      CD3 and CD28/CD3 costimulation of IL-2 production within 6 h of activation.
      Strikingly, IL-2 production induced by PMA and ionomycin was unaffected by C3
      treatment. Thus, the GTPase Rho is a novel regulator of T lymphocyte
      cytoarchitecture, and functional Rho is required for very early events regulating
      costimulation of IL-2 production in PB T cells.

PMID- 9763602
TI  - Receptor editing occurs frequently during normal B cell development.
AB  - Allelic exclusion is established in development through a feedback mechanism in
      which the assembled immunoglobulin (Ig) suppresses further V(D)J rearrangement.
      But Ig expression sometimes fails to prevent further rearrangement. In
      autoantibody transgenic mice, reactivity of immature B cells with autoantigen can
      induce receptor editing, in which allelic exclusion is transiently prevented or
      reversed through nested light chain gene rearrangement, often resulting in
      altered B cell receptor specificity. To determine the extent of receptor editing
      in a normal, non-Ig transgenic immune system, we took advantage of the fact that
      lambda light chain genes usually rearrange after kappa genes. This allowed us to
      analyze kappa loci in IgMlambda+ cells to determine how frequently in-frame kappa
      genes fail to suppress lambda gene rearrangements. To do this, we analyzed
      recombined VkappaJkappa genes inactivated by subsequent recombining sequence (RS)
      rearrangement. RS rearrangements delete portions of the kappa locus by a V(D)J
      recombinase-dependent mechanism, suggesting that they play a role in receptor
      editing. We show that RS recombination is frequently induced by, and inactivates,
      functionally rearranged kappa loci, as nearly half (47%) of the RS-inactivated
      VkappaJkappa joins were in-frame. These findings suggest that receptor editing
      occurs at a surprisingly high frequency in normal B cells.

PMID- 9763603
TI  - Cytotoxic T lymphocyte antigen 4 is induced in the thymus upon in vivo activation
      and its blockade prevents anti-CD3-mediated depletion of thymocytes.
AB  - The development of a normal T cell repertoire in the thymus is dependent on the
      interplay between signals mediating cell survival (positive selection) and cell
      death (negative selection or death by neglect). Although the CD28 costimulatory
      molecule has been implicated in this process, it has been difficult to establish
      a role for the other major costimulatory molecule, cytotoxic T lymphocyte antigen
      (CTLA)-4. Here we report that in vivo stimulation through the T cell receptor
      (TCR)-CD3 complex induces expression of CTLA-4 in thymocytes and leads to the
      association of CTLA-4 with the SH2 domain-containing phosphatase (SHP)-2 tyrosine
      phosphatase. Moreover, intrathymic CTLA-4 blockade dramatically inhibits anti-CD3
      mediated depletion of CD4+CD8+ double positive immature thymocytes. Similarly,
      anti-CD3-mediated depletion of CD4+CD8+ double positive cells in fetal thymic
      organ cultures could also be inhibited by anti-CTLA-4 antibodies. Thus, our data
      provide evidence for a role of CTLA-4 in thymic selection and suggest a novel
      mechanism contributing to the regulation of TCR-mediated selection of T cell
      repertoires.

PMID- 9763604
TI  - Regulation of anti-DNA B cells in recombination-activating gene-deficient mice.
AB  - Anti-DNA antibodies are regulated in normal individuals but are found in high
      concentration in the serum of systemic lupus erythematosus (SLE) patients and the
      MRL lpr/lpr mouse model of SLE. We previously studied the regulation of anti
      double-stranded (ds)DNA and anti-single-stranded (ss)DNA B cells in a
      nonautoimmune background by generating mice carrying immunoglobulin transgenes
      coding for anti-DNAs derived from MRL lpr/lpr. Anti-dsDNA B cells undergo
      receptor editing, but anti-ssDNA B cells seem to be functionally silenced. Here
      we have investigated how anti-DNA B cells are regulated in recombination-
      activating gene (RAG)-2-/- mice. In this setting, anti-dsDNA B cells are
      eliminated by apoptosis in the bone marrow and anti-ssDNA B cells are partially
      activated.

PMID- 9763605
TI  - Type I interferon induces inhibitory 16-kD CCAAT/ enhancer binding protein
      (C/EBP)beta, repressing the HIV-1 long terminal repeat in macrophages: pulmonary
      tuberculosis alters C/EBP expression, enhancing HIV-1 replication.
AB  - We have previously observed that HIV-1 replication is suppressed in uninflamed
      lung and increased during tuberculosis. In vitro THP-1 cell-derived macrophages
      inhibited HIV-1 replication after infection with Mycobacterium tuberculosis.
      Suppression of HIV-1 replication was associated with inhibition of the HIV-1 long
      terminal repeat (LTR) and induction of ISGF-3, a type I interferon (IFN)-specific
      transcription factor. Repression of the HIV-1 LTR required intact CCAAT/enhancer
      binding protein (C/EBP) sites. THP-1 cell-derived macrophages infected with M.
      tuberculosis, lipopolysaccharide, or IFN-beta induced the 16-kD inhibitory
      C/EBPbeta isoform and coincidentally repressed HIV-1 LTR transcription. C/EBPbeta
      was the predominant C/EBP family member produced in THP-1 macrophages during HIV
      1 LTR repression. In vivo, alveolar macrophages from uninflamed lung strongly
      expressed inhibitory 16-kD C/EBPbeta, but pulmonary tuberculosis abolished
      inhibitory C/EBPbeta expression and induced a novel C/EBP DNA binding protein.
      Therefore, in vitro, proinflammatory stimulation produces an IFN response
      inhibiting viral replication by induction of a C/EBPbeta transcriptional
      repressor. THP-1 cell-derived macrophages stimulated with type I IFN are similar
      to alveolar macrophages in the uninflamed lung in vivo. In contrast, the cellular
      immune response in active pulmonary tuberculosis disrupts this innate immunity,
      switching C/EBP expression and allowing high level viral replication.

PMID- 9763606
TI  - Integrin-mediated ras-extracellular regulated kinase (ERK) signaling regulates
      interferon gamma production in human natural killer cells.
AB  - Recent evidence indicates that integrin engagement results in the activation of
      biochemical signaling events important for regulating different cell functions,
      such as migration, adhesion, proliferation, differentiation, apoptosis, and
      specific gene expression. Here, we report that beta1 integrin ligation on human
      natural killer (NK) cells results in the activation of Ras/mitogen-activated
      protein kinase pathways. Formation of Shc-growth factor receptor-bound protein 2
      (Grb2) and Shc-proline-rich tyrosine kinase 2-Grb2 complexes are the receptor
      proximal events accompanying the beta1 integrin-mediated Ras activation. In
      addition, we demonstrate that ligation of beta1 integrins results in the
      stimulation of interferon gamma (IFN-gamma) production, which is under the
      control of extracellular signal-regulated kinase 2 activation. Overall, our data
      indicate that beta1 integrins, by delivering signals capable of triggering IFN
      gamma production, may function as NK-activating receptors.

PMID- 9763607
TI  - Coordinate activation of activator protein 1 and inflammatory cytokines in
      response to Neisseria gonorrhoeae epithelial cell contact involves stress
      response kinases.
AB  - Neisseria gonorrhoeae (Ngo), the etiologic agent of gonorrhea, induce a number of
      proinflammatory cytokines by contact to epithelial cells. Cytokine genes and a
      variety of other immune response genes are activated as a result of the
      regulatory function of immediate early response transcription factors including
      activator protein 1 (AP-1). Since it is established that phosphorylation of c
      Jun, the central component of AP-1, by the stress-activated c-Jun NH2-terminal
      kinase (JNK) increases the transcriptional activity of AP-1, we studied whether
      Ngo could induce stress response pathways involving JNK. We found that virulent
      Ngo strains induce phosphorylation and activation of JNK but not of p38 kinase.
      Analysis of a nonpathogenic Ngo strain revealed only weak JNK activation. In
      respect to the molecular components upstream of the JNK signaling cascade, we
      show that a dominant negative mutant of MAP kinase kinase 4 (MKK4) represses
      transcription of an AP-1-dependent reporter gene. Regarding upstream stress
      response factors involved in Ngo-induced MKK4/JNK/AP-1 activation, we identified
      p21-activated kinase (PAK) but not MAPK/ERK kinase kinase (MEKK1). Inhibition of
      small GTPases including Rac1 and Cdc42 by Toxin B prevented JNK and AP-1
      activation. Our results indicate that Ngo induce the activation of
      proinflammatory cytokines via a cascade of cellular stress response kinases
      involving PAK, which directs the signal from the Rho family of small GTPases to
      JNK/AP-1 activation.

PMID- 9763608
TI  - Involvement of guanosine triphosphatases and phospholipase C-gamma2 in
      extracellular signal-regulated kinase, c-Jun NH2-terminal kinase, and p38 mitogen
      activated protein kinase activation by the B cell antigen receptor.
AB  - Mitogen-activated protein (MAP) kinase family members, including extracellular
      signal-regulated kinase (ERK), c-Jun NH2-terminal kinase ( JNK), and p38 MAP
      kinase, have been implicated in coupling the B cell antigen receptor (BCR) to
      transcriptional responses. However, the mechanisms that lead to the activation of
      these MAP kinase family members have been poorly elucidated. Here we demonstrate
      that the BCR-induced ERK activation is reduced by loss of Grb2 or expression of a
      dominant-negative form of Ras, RasN17, whereas this response is not affected by
      loss of Shc. The inhibition of the ERK response was also observed in
      phospholipase C (PLC)-gamma2-deficient DT40 B cells, and expression of RasN17 in
      the PLC-gamma2-deficient cells completely abrogated the ERK activation. The PLC
      gamma2 dependency of ERK activation was most likely due to protein kinase C (PKC)
      activation rather than calcium mobilization, since loss of inositol 1,4,5
      trisphosphate receptors did not affect ERK activation. Similar to cooperation of
      Ras with PKC activation in ERK response, both PLC-gamma2-dependent signal and
      GTPase are required for BCR-induced JNK and p38 responses. JNK response is
      dependent on Rac1 and calcium mobilization, whereas p38 response requires Rac1
      and PKC activation.

PMID- 9763609
TI  - Different protein tyrosine kinases are required for B cell antigen receptor
      mediated activation of extracellular signal-regulated kinase, c-Jun NH2-terminal
      kinase 1, and p38 mitogen-activated protein kinase.
AB  - B cell antigen receptor (BCR) cross-linking activates three distinct families of
      nonreceptor protein tyrosine kinases (PTKs): src-family kinases, Syk, and Btk;
      these PTKs are responsible for initiating downstream events. BCR cross-linking in
      the chicken DT40 B cell line also activates three distinct mitogen-activated
      protein kinases (MAPKs): extracellular signal-regulated kinase (ERK)2, c-jun NH2
      terminal kinase (JNK)1, and p38 MAPK. To dissect the functional roles of these
      PTKs in MAPK signaling, activation of MAPKs was examined in various PTK-deficient
      DT40 cells. BCR-mediated activation of ERK2, although maintained in Lyn-deficient
      cells, was abolished in Syk-deficient cells and partially inhibited in Btk
      deficient cells, indicating that BCR-mediated ERK2 activation requires Syk and
      that sustained ERK2 activation requires Btk. BCR-mediated JNK1 activation was
      maintained in Lyn-deficient cells but abolished in both Syk- and Btk-deficient
      cells, suggesting that JNK1 is activated via a Syk- and Btk-dependent pathway.
      Consistent with this, BCR-mediated JNK1 activation was dependent on intracellular
      calcium and phorbol myristate acetate-sensitive protein kinase Cs. In contrast,
      BCR-mediated p38 MAPK activation was detected in all three PTK-deficient cells,
      suggesting that no single PTK is essential. However, BCR-mediated p38 MAPK
      activation was abolished in Lyn/Syk double deficient cells, demonstrating that
      either Lyn or Syk alone may be sufficient to activate p38 MAPK. Our data show
      that BCR-mediated MAPK activation is regulated at the level of the PTKs.

PMID- 9763610
TI  - Expression of interleukin 9 in the lungs of transgenic mice causes airway
      inflammation, mast cell hyperplasia, and bronchial hyperresponsiveness.
AB  - Interleukin (IL)-9, a pleiotropic cytokine produced by the Th2 subset of T
      lymphocytes has been proposed as product of a candidate gene responsible for
      asthma. Its wide range of biological functions on many cell types involved in the
      allergic immune response suggests a potentially important role in the complex
      pathogenesis of asthma. To investigate the contributions of IL-9 to airway
      inflammation and airway hyperresponsiveness in vivo, we created transgenic mice
      in which expression of the murine IL-9 cDNA was regulated by the rat Clara cell
      10 protein promoter. Lung selective expression of IL-9 caused massive airway
      inflammation with eosinophils and lymphocytes as predominant infiltrating cell
      types. A striking finding was the presence of increased numbers of mast cells
      within the airway epithelium of IL-9-expressing mice. Other impressive pathologic
      changes in the airways were epithelial cell hypertrophy associated with
      accumulation of mucus-like material within nonciliated cells and increased
      subepithelial deposition of collagen. Physiologic evaluation of IL-9-expressing
      mice demonstrated normal baseline airway resistance and markedly increased airway
      hyperresponsiveness to inhaled methacholine. These findings strongly support an
      important role for IL-9 in the pathogenesis of asthma.

PMID- 9763612
TI  - The inositol polyphosphate 5-phosphatase ship is a crucial negative regulator of
      B cell antigen receptor signaling.
AB  - Ship is an Src homology 2 domain containing inositol polyphosphate 5-phosphatase
      which has been implicated as an important signaling molecule in hematopoietic
      cells. In B cells, Ship becomes associated with Fcgamma receptor IIB
      (FcgammaRIIB), a low affinity receptor for the Fc portion of immunoglobulin
      (Ig)G, and is rapidly tyrosine phosphorylated upon B cell antigen receptor (BCR)
      FcgammaRIIB coligation. The function of Ship in lymphocytes was investigated in
      Ship-/- recombination-activating gene (Rag)-/- chimeric mice generated from gene
      targeted Ship-/- embryonic stem cells. Ship-/-Rag-/- chimeras showed reduced
      numbers of B cells and an overall increase in basal serum Ig. Ship-/- splenic B
      cells displayed prolonged Ca2+ influx, increased proliferation in vitro, and
      enhanced mitogen-activated protein kinase (MAPK) activation in response to BCR
      FcgammaRIIB coligation. These results demonstrate that Ship plays an essential
      role in FcgammaRIIB-mediated inhibition of BCR signaling, and that Ship is a
      crucial negative regulator of Ca2+ flux and MAPK activation.

PMID- 9763611
TI  - Transgenic mice overexpressing the complement inhibitor crry as a soluble protein
      are protected from antibody-induced glomerular injury.
AB  - Complement receptor 1-related gene/protein y (Crry) is a potent murine membrane
      complement regulator that inhibits classical and alternative pathway C3
      convertases. In nephrotoxic serum (NTS) nephritis, injected antibodies (Abs) bind
      to glomeruli, leading to complement activation and subsequent glomerular injury
      and albuminuria. To study the phenotypic effects of continuous complement pathway
      blockade, transgenic mice were created that express recombinant soluble (rs) Crry
      directed by the broadly active and heavy metal-inducible metallothionein-I
      promoter. One transgenic line expressing high levels of rsCrry was propagated.
      Serum rsCrry levels were 18.7 +/- 2.7 microg/ml (n = 5) at basal level and
      increased to 118.1 +/- 20.6 microg/ml 4 d after addition of zinc to the drinking
      water. By reverse transcription polymerase chain reaction (RT-PCR), transgene
      messenger (m)RNA was present in liver, kidney, brain, lung, and spleen, but not
      in heart. By in situ RT-PCR analysis of kidneys, transgene mRNA was widely
      expressed both in renal glomeruli and tubules. Urinary excretion of rsCrry was
      113.4 +/- 22.4 microg/ml with a fractional excretion relative to creatinine of
      13.2 +/- 2.7%, consistent with local renal production of rsCrry and secretion
      into urine. The founder and all transgene positive adult animals have remained
      healthy with no mortality or apparent phenotypic abnormalities, including
      infection or immune complex disease. To determine whether rsCrry blocked
      complement-mediated injury, NTS nephritis was induced by injection of NTS
      immunoglobulin (Ig)G, followed by an 18-h urine collection to quantitate the
      excretion of albumin as a measure of glomerular injury. In transgene-negative
      littermates (n = 15), transgene-positive animals (n = 10), and transgene-positive
      animals fed zinc (n = 10), albuminuria was 4,393 +/- 948, 1,783 +/- 454, and
      1,057 +/- 277 microg/mg creatinine, respectively (P < 0.01 by ANOVA). Glomerular
      C3 was evident by immunofluorescence staining in 12/15 transgene-negative
      animals, but in none of the transgene-positive animals fed zinc. Thus, we have
      produced the first transgenic animals that overexpress a soluble C3 convertase
      inhibitor. rsCrry expression markedly ameliorates an Ab-induced disease model in
      vivo. These results support the hypothesis that continuous complement inhibition
      at the C3 convertase step is feasible and effective in complement-mediated injury
      states.

PMID- 9763613
TI  - A critical role of the p75 tumor necrosis factor receptor (p75TNF-R) in organ
      inflammation independent of TNF, lymphotoxin alpha, or the p55TNF-R.
AB  - Despite overwhelming evidence that enhanced production of the p75 tumor necrosis
      factor receptor (p75TNF-R) accompanies development of specific human inflammatory
      pathologies such as multi-organ failure during sepsis, inflammatory liver
      disease, pancreatitis, respiratory distress syndrome, or AIDS, the function of
      this receptor remains poorly defined in vivo. We show here that at levels
      relevant to human disease, production of the human p75TNF-R in transgenic mice
      results in a severe inflammatory syndrome involving mainly the pancreas, liver,
      kidney, and lung, and characterized by constitutively increased NF-kappaB
      activity in the peripheral blood mononuclear cell compartment. This process is
      shown to evolve independently of the presence of TNF, lymphotoxin alpha, or the
      p55TNF-R, although coexpression of a human TNF transgene accelerated pathology.
      These results establish an independent role for enhanced p75TNF-R production in
      the pathogenesis of inflammatory disease and implicate the direct involvement of
      this receptor in a wide range of human inflammatory pathologies.

PMID- 9763614
TI  - Inhibition of complement regulation is key to the pathogenesis of active Heymann
      nephritis.
AB  - Crry (complement receptor 1-related protein/gene y) is a key cellular complement
      regulator in rodents. It is also present in Fx1A, the renal tubular preparation
      used to immunize rats to induce active Heymann nephritis (HN), a model of
      membranous nephropathy. We hypothesized that rats immunized with anti-Fx1A
      develop autoantibodies (auto-Abs) to Crry as well as to the megalin-containing HN
      antigenic complex, and that anti-Crry Abs promote the development of injury in HN
      by neutralizing the complement regulatory activity of Crry. Rats immunized with
      Fx1A lacking Crry remained free of proteinuria and glomerular deposits of C3
      during a 10-wk follow-up despite typical granular immunoglobulin (Ig)G deposits
      in glomeruli. Anti-Fx1A auto-Abs were present in their sera at levels that were
      not different from sera pooled from proteinuric rats with HN induced with
      nephritogenic Fx1A. Passive administration of sheep anti-Crry Abs to rats
      immunized with Crry-deficient Fx1A led to proteinuria and glomerular C3
      deposition, which were not seen in such rats injected with preimmune IgG, nor in
      rats with collagen-induced arthritis injected with anti-Crry IgG. To directly
      examine the role of Crry in HN, rats were immunized with Crry-deficient Fx1A
      reconstituted with rCrry. This led to typical HN, with 8 out of 15 rats
      developing proteinuria within 14 wk. Moreover, the extent of glomerular C3
      deposition correlated with proteinuria, and anti-Crry Abs were present in
      glomerular eluates. Thus, Crry is a key nephritogenic immunogen in Fx1A.
      Formation of neutralizing auto-Abs to Crry impairs its function, leading to
      unrestricted complement activation by Abs reactive with the HN antigenic complex
      on the epithelial cell surface.

PMID- 9763615
TI  - Immature dendritic cells phagocytose apoptotic cells via alphavbeta5 and CD36,
      and cross-present antigens to cytotoxic T lymphocytes.
AB  - Dendritic cells, but not macrophages, efficiently phagocytose apoptotic cells and
      cross-present viral, tumor, and self-antigens to CD8(+) T cells. This in vitro
      pathway corresponds to the in vivo phenomena of cross-priming and cross
      tolerance. Here, we demonstrate that phagocytosis of apoptotic cells is
      restricted to the immature stage of dendritic cell (DC) development, and that
      this process is accompanied by the expression of a unique profile of receptors,
      in particular the alphavbeta5 integrin and CD36. Upon maturation, these receptors
      and, in turn, the phagocytic capacity of DCs, are downmodulated. Macrophages
      engulf apoptotic cells more efficiently than DCs, and although they express many
      receptors that mediate this uptake, they lack the alphavbeta5 integrin.
      Furthermore, in contrast to DCs, macrophages fail to cross-present antigenic
      material contained within the engulfed apoptotic cells. Thus, DCs use unique
      pathways for the phagocytosis, processing, and presentation of antigen derived
      from apoptotic cells on class I major histocompatibility complex. We suggest that
      the alphavbeta5 integrin plays a critical role in the trafficking of exogenous
      antigen by immature DCs in this cross-priming pathway.

PMID- 9763616
TI  - The interleukin 2 receptor alpha chain/CD25 promoter is a target for nuclear
      factor of activated T cells.
AB  - The expression of the murine interleukin (IL)-2 receptor alpha chain/CD25 is
      strongly induced at the transcriptional level after T cell activation. We show
      here that nuclear factor of activated T cell (NF-AT) factors are involved in the
      control of CD25 promoter induction in T cells. NF-ATp and NF-ATc bind to two
      sites around positions -585 and -650 located upstream of the proximal CD25
      promoter. Immediately 3' from these NF-AT motifs, nonconsensus sites are located
      for the binding of AP-1-like factors. Mutations of sites that suppress NF-AT
      binding impair the induction and strong NF-ATp-mediated transactivation of the
      CD25 promoter in T cells. In T lymphocytes from NF-ATp-deficient mice, the
      expression of CD25 is severely impaired, leading to a delayed IL-2 receptor
      expression after T cell receptor (TCR)/CD3 stimulation. Our data indicate an
      important role for NF-AT in the faithful expression of high affinity IL-2
      receptors and a close link between the TCR-mediated induction of IL-2 and IL-2
      receptor alpha chain promoters, both of which are regulated by NF-AT factors.

PMID- 9763617
TI  - Essential and partially overlapping role of CD3gamma and CD3delta for development
      of alphabeta and gammadelta T lymphocytes.
AB  - CD3gamma and CD3delta are two highly related components of the T cell receptor
      (TCR)-CD3 complex which is essential for the assembly and signal transduction of
      the T cell receptor on mature T cells. In gene knockout mice deficient in either
      CD3delta or CD3gamma, early thymic development mediated by pre-TCR was either
      undisturbed or severely blocked, respectively, and small numbers of TCR
      alphabeta+ T cells were detected in the periphery of both mice. gammadelta T cell
      development was either normal in CD3delta-/- mice or partially blocked in
      CD3gamma-/- mice. To examine the collective role of CD3gamma and CD3delta in the
      assembly and function of pre-TCR and in the development of gammadelta T cells, we
      generated a mouse strain with a disruption in both CD3gamma and CD3delta genes
      (CD3gammadelta-/-). In contrast to mice deficient in either CD3gamma or CD3delta
      chains, early thymic development mediated by pre-TCR is completely blocked, and
      TCR-alphabeta+ or TCR-gammadelta+ T cells were absent in the CD3gammadelta-/-
      mice. Taken together, these studies demonstrated that CD3gamma and CD3delta play
      an essential, yet partially overlapping, role in the development of both
      alphabeta and gammadelta T cell lineages.

PMID- 9763618
TI  - Stimulus-dependent synergism of the antiapoptotic tumor necrosis factor receptor
      associated factor 2 (TRAF2) and nuclear factor kappaB pathways.
AB  - Tumor necrosis factor (TNF) signaling leads to pleiotropic responses in a wide
      range of cell types, in part by activating antiapoptotic and proapoptotic
      signaling pathways. Thus, although TNF can cause apoptosis and may prove useful
      in the treatment of malignancies, most cells are resistant to TNF-induced cell
      death unless de novo protein synthesis is inhibited. Previous studies suggested
      that TNF activation of the nuclear factor (NF)-kappaB transcription factor family
      antagonizes the proapoptotic signals initiated by TNF-alpha. TNF receptor
      associated factor (TRAF)2 has also been shown to mediate crucial antiapoptotic
      signals during TNF stimulation, yet is not essential in activation of NF-kappaB
      under physiologic conditions, thus raising questions about the relationship
      between these antiapoptotic pathways. We report here that inhibition of TRAF2 and
      NF-kappaB function in primary cells, by coexpression of a constitutive repressor
      of multiple NF-kappaB/Rel proteins (IkappaBalpha.DN) and a dominant negative form
      of TRAF2 (TRAF2.DN), synergistically enhanced TNF-induced apoptosis. The effects
      were stimulus dependent, such that neither inhibitory molecule affected Fas- and
      daunorubicin-induced apoptosis to the same degree as TNF-induced death. These
      findings indicate that the NF-kappaB and TRAF2 pathways activate independent
      antiapoptotic mechanisms which act in concert to suppress the proapoptotic
      signals induced by TNF-alpha.

PMID- 9763619
TI  - Regulation of L-selectin-mediated rolling through receptor dimerization.
AB  - L-selectin binding activity for its ligand expressed by vascular endothelium is
      rapidly and transiently increased after leukocyte activation. To identify
      mechanisms for upregulation and assess how this influences leukocyte/endothelial
      cell interactions, cell-surface dimers of L-selectin were induced using the
      coumermycin-GyrB dimerization strategy for cross-linking L-selectin cytoplasmic
      domains in L-selectin cDNA-transfected lymphoblastoid cells. Coumermycin- induced
      L-selectin dimerization resulted in an approximately fourfold increase in binding
      of phosphomanan monoester core complex (PPME), a natural mimic of an L-selectin
      ligand, comparable to that observed after leukocyte activation. Moreover, L
      selectin dimerization significantly increased (by approximately 700%) the number
      of lymphocytes rolling on vascular endothelium under a broad range of
      physiological shear stresses, and significantly slowed their rolling velocities.
      Therefore, L-selectin dimerization may explain the rapid increase in ligand
      binding activity that occurs after leukocyte activation and may directly
      influence leukocyte migration to peripheral lymphoid tissues or to sites of
      inflammation. Inducible oligomerization may also be a common mechanism for
      rapidly upregulating the adhesive or ligand-binding function of other cell
      surface receptors.

PMID- 9763620
TI  - Muscle geometry.

PMID- 9763621
TI  - The generation of directionally selective responses in the retina.

PMID- 9763622
TI  - An ether -a-go-go K+ current, Ih-eag, contributes to the hyperpolarization of
      human fusion-competent myoblasts.
AB  - 1. Two early signs of human myoblast commitment to fusion are membrane potential
      hyperpolarization and concomitant expression of a non-inactivating delayed
      rectifier K+ current, IK(NI). This current closely resembles the outward K+
      current elicited by rat ether-a-go-go (r-eag) channels in its range of potential
      for activation and unitary conductance. 2. It is shown that activation kinetics
      of IK(NI), like those of r-eag, depend on holding potential and on [Mg2+]o, and
      that IK(NI), like r-eag, is reversibly inhibited by a rise in [Ca2+]i. 3. Forced
      expression of an isolated human ether-a-go-go K+ channel (h-eag) cDNA in
      undifferentiated myoblasts generates single-channel and whole-cell currents with
      remarkable similarity to IK(NI). 4. h-eag current (Ih-eag) is reversibly
      inhibited by a rise in [Ca2+]i, and the activation kinetics depend on holding
      potential and [Mg2+]o. 5. Forced expression of h-eag hyperpolarizes
      undifferentiated myoblasts from -9 to -50 mV, the threshold for the activation of
      both Ih-eag and IK(NI). Similarly, the higher the density of IK(NI), the more
      hyperpolarized the resting potential of fusion-competent myoblasts. 6. It is
      concluded that h-eag constitutes the channel underlying IK(NI) and that it
      contributes to the hyperpolarization of fusion-competent myoblasts. To our
      knowledge, this is the first demonstration of a physiological role for a
      mammalian eag K+ channel.

PMID- 9763623
TI  - Separable effects of human Kvbeta1.2 N- and C-termini on inactivation and
      expression of human Kv1.4.
AB  - 1. The Kvbeta subunits of voltage-gated K+ channels alter the functional
      expression and gating of non- or slowly inactivating Kvalpha1 subunits via two
      separate domains. To determine how Kvbeta subunits modulate a rapidly
      inactivating Kvalpha1 subunit, we did two-microelectrode voltage clamp
      experiments on human Kv1.4 voltage-gated K+ channels expressed heterologously in
      Xenopus oocytes. In addition we tested a slowly inactivating mutant of Kv1.4
      lacking amino acids 2-146 of the N-terminal alpha-ball domain (Kv1. 4DeltaN2
      146). Kv1.4 or Kv1.4DeltaN2-146 were co-expressed with either rat Kvbeta2 or
      human Kvbeta1.2. To separate domain effects, we also used a mutant of Kvbeta1.2
      lacking the unique 79 amino acid N-terminal beta-ball domain (Kvbeta1-C). 2. For
      the mutant Kv1.4DeltaN2-146 we found that Kvbeta1-C or Kvbeta2 increased current
      amplitude without altering activation or inactivation. By contrast Kvbeta1.2
      produced rapid inactivation and slowed deactivation due to block produced by the
      beta-ball. The beta-ball also increased the rate of C-type inactivation in 5 mM,
      but not 50 mM, external K+ consistent with an effect of blockade on K+ efflux. 3.
      For Kv1.4, Kvbeta1-C produced a voltage-independent increase in the rate of
      inactivation and shifted the inactivation curve to more hyperpolarized
      potentials, but had no effect on deactivation. Kvbeta1-C, Kvbeta2 and Kvbeta1.2
      slowed recovery from inactivation similarly, thereby excluding involvement of the
      beta-ball. Kvbeta1.2 produced an additional more rapid, voltage-dependent
      component of inactivation, significantly reduced peak outward current and shifted
      steady-state inactivation towards hyperpolarized potentials. 4. Yeast two-hybrid
      studies showed that alpha-beta interaction was restricted to the N-terminus of
      Kv1.4 and the C-terminus of Kvbeta1. 2 or Kvbeta2. Direct interaction with the
      alpha-ball did not occur. Our interpretation is that Kvbeta1-C and Kvbeta2
      enhanced N-type inactivation produced by the Kv1.4 alpha-ball allosterically. 5.
      We propose that Kvbeta1.2 has three effects on Kv1.4, the first two of which it
      shares with Kvbeta2. First, Kvbeta1-C and Kvbeta2 have a current-enhancing
      effect. Second, Kvbeta1-C and Kvbeta2 increase block by the alpha-ball
      allosterically. Third, the beta-ball of Kbeta1.2 directly blocks both Kv1.4 and
      Kv1.4DeltaN2-146. When both alpha- and beta-balls are present, competition for
      their respective binding sites slows the block produced by either ball.

PMID- 9763624
TI  - Fibre type-specific gene expression activated by chronic electrical stimulation
      of adult mouse skeletal muscle fibres in culture.
AB  - 1. Fast-twitch skeletal muscle fibres were enzymatically dissociated from adult
      mouse flexor digitorum brevis (FDB) muscles and maintained in culture without or
      with chronic low frequency stimulation (one 5 s train of 5 Hz pulses per minute)
      for up to 6 days. Single fibre reverse transcriptase-polymerase chain reaction
      was conducted to coamplify beta-myosin heavy chain (beta-MHC) and alpha-skeletal
      actin mRNA from the same fibre. 2. Chronic low frequency electrical stimulation
      of FDB fibres in culture increased the level of mRNA for beta-MHC. In
      unstimulated fibres there was a slight decline in the beta-MHC mRNA level. As an
      internal control there was no increase in the level of mRNA for alpha-actin in
      the identical individual stimulated or unstimulated fibres. 3. Neither the
      percentage of fibres exhibiting beta-MHC protein nor the Ca2+ transients recorded
      from individual fibres subjected to the same pattern of stimulation showed any
      difference between stimulated and unstimulated fibres over the period in culture.
      4. This system provides a convenient in vitro model system for studying activity
      dependent control of fibre type-specific gene expression in adult skeletal muscle
      fibres in culture.

PMID- 9763625
TI  - Thiophosphorylation of myosin light chain increases rigor stiffness of rabbit
      smooth muscle.
AB  - 1. The effect of thiophosphorylation of the regulatory myosin light chain (MLC20)
      on rigor stiffness was determined in permeabilized rabbit bladder smooth muscle.
      2. Rigor stiffness of alpha-toxin-permeabilized smooth muscle was significantly
      increased by thiophosphorylation of MLC20. This increase may have been due to
      partial shortening (melting) in the proximal rod region and/or stiffening of the
      regulatory domain of the myosin head. 3. We suggest that phosphorylation of
      MLC20, by increasing the stiffness of the S1 lever arm and/or S2 hinge regions of
      the myosin molecule, favours separation of the two phosphorylated heads and
      consequent deinhibition of motor domain activity.

PMID- 9763626
TI  - Chronic hypoxia reduces adenosine A2A receptor-mediated inhibition of calcium
      current in rat PC12 cells via downregulation of protein kinase A.
AB  - 1. Adenosine has been shown to decrease Ca2+ current (ICa) and attenuate the
      hypoxia-induced enhancement of intracellular free Ca2+ ([Ca2+]i) in oxygen
      sensitive rat phaeochromocytoma (PC12) cells. These effects are mediated via the
      adenosine A2A receptor and protein kinase A (PKA). The current study was
      undertaken to determine the effects of adenosine on Ca2+ current and hypoxia
      induced change in [Ca2+]i during chronic hypoxia. 2. Whole cell patch-clamp
      studies revealed that the effect of adenosine on ICa was significantly reduced
      when PC12 cells were exposed to hypoxia (10 % O2) for 24 and 48 h. 3. Ca2+
      imaging studies using fura-2 revealed that the anoxia-induced increase in [Ca2+]i
      was significantly enhanced when PC12 cells were exposed to 10 % O2 for up to 48
      h. In contrast, the inhibitory effects of adenosine on anoxia-induced elevation
      of [Ca2+]i was significantly blunted in PC12 cells exposed to hypoxia for 48 h.
      4. Northern blot analysis revealed that mRNA for the A2A receptor, which is the
      only adenosine receptor subtype expressed in PC12 cells, was significantly
      upregulated by hypoxia. Radioligand binding analysis with [3H]CGS21680, a
      selective A2A receptor ligand, showed that the number of adenosine A2A receptor
      binding sites was similarly increased during exposure to 10% O2 for 48 h. 5. PKA
      enzyme activity was significantly inhibited when PC12 cells were exposed to 10%
      O2 for 24 and 48 h. However, we found that hypoxia failed to induce change in
      adenosine- and forskolin-stimulated adenylate cyclase enzyme activity. Chronic
      hypoxia also did not alter the immunoreactivity level of the G protein Gsalpha,
      an effector of the A2 signalling pathway. 6. Whole cell patch-clamp analysis
      showed that the effect of 8-bromo-cAMP, an activator of PKA, on ICa was
      significantly attenuated during 48 h exposure to 10% O2.7. We conclude therefore
      that the reduced effect of adenosine on ICa and [Ca2+]i in PC12 cells exposed to
      chronic hypoxia is due to hypoxia-induced downregulation of PKA. This mechanism
      may serve to reduce the negative feedback on ICa and [Ca2+]i by adenosine and
      therefore maintain enhanced membrane excitability of PC12 cells during long-term
      hypoxia.

PMID- 9763627
TI  - Contrasting Ca2+ channel subtypes at cell bodies and synaptic terminals of rat
      anterioventral cochlear bushy neurones.
AB  - 1. Whole-cell patch clamp recordings were made from bushy cells of the
      anterioventral cochlear nucleus (aVCN) and their synaptic terminals (calyx of
      Held) in the medial nucleus of the trapezoid body (MNTB). 2. Both high voltage
      activated (HVA) and low voltage-activated (LVA) calcium currents were present in
      acutely dissociated aVCN neurones and in identified bushy neurones from a
      cochlear nucleus slice. 3. The transient LVA calcium current activated rapidly on
      depolarization (half-activation, -59 mV) and inactivated during maintained
      depolarization (half-inactivation, -89 mV). This T-type current was observed in
      somatic recordings but was absent from presynaptic terminals. 4. On the basis of
      their pharmacological sensitivity, P/Q-type Ca2+ channels accounted for only 6 %
      of the somatic HVA, while L-, N- and R-type Ca2+ channels each accounted for
      around one-third of the somatic calcium current. 5. The divalent permeabilities
      of these native calcium channels were compared. The Ba2+/Ca2+ conductance ratios
      of the somatic HVA and LVA channels were 1.4 and 0.7, respectively. The
      conductance ratio of the presynaptic HVA current was 0.9, significantly lower
      that that of the somatic HVA current. 6. We conclude that LVA currents are
      expressed in the bushy cell body, but are not localized to the excitatory
      synaptic terminal. All of the HVA current subtypes are expressed in bushy cells,
      but there is a strong polarity to their localization; P-type contribute little to
      somatic currents but predominate at the synaptic terminal; L-, N- and R-types
      dominate at the soma, but contribute negligibly to calcium currents in the
      terminal.

PMID- 9763628
TI  - Local calcium release in mammalian skeletal muscle.
AB  - 1. Fluo-3 fluorescence associated with Ca2+ release was recorded with confocal
      microscopy in single muscle fibres mechanically dissected from fast twitch muscle
      of rats or frogs, voltage clamped in a two Vaseline-gap chamber. 2. Interventions
      that elicited Ca2+ sparks in frog skeletal muscle (low voltage depolarizations,
      application of caffeine) generated in rat fibres images consistent with
      substantial release from triadic regions, but devoid of resolvable discrete
      events. Ca2+ sparks were never observed in adult rat fibres. In contrast, sparks
      of standard morphology were abundant in myotubes from embryonic mice. 3.
      Depolarization-induced gradients of fluorescence between triadic and surrounding
      regions (which are proportional to Ca2+ release flux) peaked at about 20 ms and
      then decayed to a steady level. Gradients were greater in frog fibres than in rat
      fibres. The ratio of peak over steady gradient (R) was steeply voltage dependent
      in frogs, reaching a maximum of 4.8 at -50 mV (n = 7). In rats, R had an
      essentially voltage-independent value of 2.3 (n = 5). 4. Ca2+-induced Ca2+
      release, resulting in concerted opening of several release channels, is thought
      to underlie Ca2+ sparks and the peak phase of release in frog skeletal muscle. A
      diffuse 'small event' release, similar to that observed in these rats, is also
      present in frogs and believed to be directly activated by voltage. The present
      results suggest that in these rat fibres there is little contribution by CICR to
      Ca2+ release triggered by depolarization, and a lack of concerted channel
      opening.

PMID- 9763629
TI  - alpha-adrenergic stimulation of cytosolic Ca2+ oscillations and exocytosis in
      identified rat corticotrophs.
AB  - 1. The patch clamp technique was used in conjunction with a fluorescent Ca2+
      indicator (indo-1, or indo-1FF) to measure simultaneously cytosolic Ca2+
      concentration ([Ca2+]i), ionic current and changes in membrane capacitance in
      single rat corticotrophs identified with the reverse haemolytic plaque assay. 2.
      Application of the adrenocorticotropin (ACTH) secretagogue noradrenaline (NA;
      norepinephrine), triggered [Ca2+]i oscillation in corticotrophs via alpha
      adrenergic receptors and the guanosine trisphosphate (GTP) binding protein
      coupled phosphoinositide pathway. 3. Simultaneous measurement of [Ca2+]i and
      capacitance shows that exocytosis was triggered during the first cycle of NA
      induced [Ca2+]i oscillation and the mean increase in cell membrane surface area
      was 1.4 +/- 0.3 % (n = 6). 4. When Ca2+ was directly released from the inositol
      1,4, 5 trisphosphate (IP3)-sensitive store via flash photolysis of caged IP3, the
      mean increase in cell surface area was 1.5 +/- 0.5 % (n = 6). Thus, NA-stimulated
      ACTH secretion in rat corticotrophs is closely coupled to intracellular Ca2+
      release. 5. Large and rapid elevation of [Ca2+]i (>15 microM) via flash
      photolysis of caged Ca2+ triggered two phases of exocytosis: a rapid exocytic
      burst that was complete in approximately 100 ms and a slow burst that continued
      for many seconds. 6. The rapid exocytic burst reflected the exhaustion of a pool
      of readily releasable granules and, on average, increased the cell surface by 2.8
      +/- 0.1 % (n = 14). 7. We suggest that the relatively weak exocytic response in
      corticotrophs during intracellular Ca2+ release may be partially attributed to a
      smaller pool of readily releasable granules.

PMID- 9763630
TI  - Cytoplasmic terminus domains of Kir6.x confer different nucleotide-dependent
      gating on the ATP-sensitive K+ channel.
AB  - 1. In order to investigate the structural basis for the nucleotide-dependent
      gating of ATP-sensitive K+ channels (KATP), Kir6.1 (uKATP-1), Kir6.2 (BIR1) and
      chimeric channels were co-expressed with a common subtype of sulphonylurea
      receptor, SUR1, in COS7 cells. Representing the amino terminal domain
      transmembrane domain-carboxyl-terminal domain of Kir6.1 as 1-1-1 and of Kir6.2 as
      2-2-2, chimeric Kir6.x channels were constructed by swapping the amino and/or
      carboxyl terminal domains between Kir6.1 and Kir6.2 to give the chimeric x-1-x
      channels 1-1-2, 2-1-1 and 2-1-2, and the chimeric x-2-x channels 2-2-1, 1-2-2 and
      1-2-1. 2. Inside-out patch clamp experiments revealed that both wild-type Kir6.1
      and Kir6.2 formed inwardly rectifying K+ channels. Single-channel conductances
      were 36.3 and 66.1 pS, respectively. Chimeric x-1-x channels, whose transmembrane
      domain was that of Kir6.1, showed similar ion-pore properties to wild-type
      Kir6.1. Likewise, chimeric x-2-x channels had similar ion-pore properties to wild
      type Kir6.2. 3. Wild-type Kir6.1 and Kir6.2 possessed distinct gating properties
      towards intracellular nucleotides. The activity of Kir6.1 was entirely dependent
      on Mg2+ and nucleotide diphosphates (NDPs) such as UDP. In contrast, Kir6.2 was
      activated upon excision of patch membrane. When Kir6.2 underwent rundown, UDP
      reactivated the channel. 4. In order to eliminate UDP dependence from Kir6.1, it
      was necessary to replace both N- and C-termini; chimera 2-1-2 opened in UDP-free
      conditions. With Kir6.2, substitution of the N-terminus with that of Kir6.1
      conferred UDP dependence on chimeras 1-2-2 and 1-2-1. Chimera 2-2-1 opened in UDP
      free conditions, but UDP potentiated the channel activity by > 20-fold. 5. The
      kinetics of UDP-dependent activation were significantly different between Kir6.1
      and Kir6.2. Kir6.1 maximally activated by UDP was sensitive to intracellular ATP,
      although its ATP sensitivity was significantly lower than that of Kir6.2 measured
      in identical conditions. The kinetics of UDP-dependent activation and ATP
      sensitivity could be transferred between Kir6.1 and Kir6.2 only when both N- and
      C-termini were replaced. We therefore concluded that nucleotide-dependent gating
      was regulated by the N- and C-terminal domains irrespective of the transmembrane
      domains.

PMID- 9763632
TI  - Anoxia differentially modulates multiple K+ currents and depolarizes neonatal rat
      adrenal chromaffin cells.
AB  - 1. Using perforated-patch, whole cell recording, we investigated the membrane
      mechanisms underlying O2 chemosensitivity in neonatal rat adrenomedullary
      chromaffin cells (AMC) bathed in extracellular solution containing tetrodotoxin
      (TTX; 0.5-1 microM), with or without blockers of calcium entry. 2. Under voltage
      clamp, low PO2 (0-15 mmHg) caused a graded and reversible suppression in
      macroscopic outward K+ current. The suppression during anoxia (PO2 = 0 mmHg) was
      approximately 35% (voltage step from -60 to +30 mV) and was due to a combination
      of several factors: (i) suppression of a cadmium-sensitive, Ca2+-dependent K+
      current, IK(CaO2); (ii) suppression of a Ca2+-insensitive, delayed rectifier type
      K+ current, IK(VO2); (iii) activation of a glibenclamide- (and Ca2+)-sensitive
      current, IK(ATP). 3. During normoxia (PO2 = 150 mmHg), application of pinacidil
      (100 microM), an ATP-sensitive potassium channel (KATP) activator, increased
      outward current density by 45.0 +/- 7.0 pA pF-1 (step from -60 to + 30 mV),
      whereas the KATP blocker glibenclamide (50 microM) caused only a small
      suppression by 6.3 +/- 4.0 pA pF-1. In contrast, during anoxia the presence of
      glibenclamide resulted in a substantial reduction in outward current density by
      24.9 +/- 7.9 pA pF-1, which far exceeded that seen in its absence. Thus,
      activation of IK(ATP) by anoxia appears to reduce the overall K+ current
      suppression attributable to the combined effects of IK(CaO2) and IK(VO2). 4.
      Pharmacological tests revealed that IK(CaO2) was carried predominantly by maxi-K+
      or BK potassium channels, sensitive to 50-100 nM iberiotoxin; this current also
      accounted for the major portion (approximately 60%) of the anoxic suppression of
      outward current. Tetraethylammonium (TEA; 10-20 mM) blocked all of the anoxia
      sensitive K+ currents recorded under voltage clamp, i.e. IK(CaO2), IK(VO2) and
      IK(ATP). 5. Under current clamp, anoxia depolarized neonatal AMC by 10-15 mV from
      a resting potential of approximately -55 mV. At least part of this depolarization
      persisted in the presence of either TEA, Cd2+, 4-aminopyridine or charybdotoxin,
      suggesting the presence of anoxia-sensitive mechanisms additionalto those
      revealed under voltage clamp. In Na+/Ca2+-free solutions, the membrane
      hyperpolarized, though at least a portion of the anoxia-induced depolarization
      persisted. 6. In the presence of glibenclamide, the anoxia-induced depolarization
      increased significantly to approximately 25 mV, suggesting that activation of
      KATP channels may function to attenuate the anoxia-induced depolarization or
      receptor potential.

PMID- 9763631
TI  - Non-receptor-mediated activation of IK(ATP) and inhibition of IK(ACh) by
      diadenosine polyphosphates in guinea-pig atrial myocytes.
AB  - 1. The effects of diadenosine polyphosphates (APnA, where n = 4-6) were studied
      on beating frequency of perfused guinea-pig hearts and on muscarinic K+ current
      (IK(ACh)) and ATP-regulated K+ current (IK(ATP)) in atrial myocytes from guinea
      pig hearts using whole-cell voltage clamp. 2. Bradycardia induced by APnA in
      perfused hearts was completely inhibited by 8-cyclopentyl- 1,3-dipropylxanthine
      (CPX, 20 microM), a selective antagonist at A1 adenosine receptors, and was
      augmented by dipyridamole (Dipy), an inhibitor of cellular adenosine (Ado)
      uptake. 3. Whereas exposure of atrial myocytes to Ado (100 microM) within about 1
      s induced a significant whole-cell IK(ACh), APnA up to 1 mM applied for some tens
      of seconds failed to activate IK(ACh). If present for periods > 2 min, APnA
      caused inhibition of agonist-evoked IK(ACh) and activation of a weakly inward
      rectifying K+ current, which was identified as IK(ATP) by its sensitivity to
      glibenclamide and its current-voltage curve. 4. The actions of extracellular APnA
      on IK(ACh) and IK(ATP) were mimicked by intracellular loading of compounds via
      the patch clamp pipette and by intracellular loading of AMP. 5. The results from
      isolated myocytes exclude APnA acting as A1 agonists. It is suggested that
      myocytes can take up APnA, which are degraded to AMP. In the presence of ATP, AMP
      is converted to ADP, a physiological activator of ATP-regulated K+ channels, by
      adenylate kinase. A similar mechanism resulting in a reduction of the [GTP]/[GDP]
      ratio might be responsible for inhibition of IK(ACh). 6. In the perfused heart
      and other multicellular cardiac preparations the actions of APnA are mediated by
      Ado via A1 receptors. It is suggested that APnA in multicellular cardiac tissue
      are hydrolysed by an ectohydrolase to yield AMP which is converted to Ado by
      ectonucleotidases.

PMID- 9763633
TI  - Involvement of PKC-alpha in regulatory volume decrease responses and activation
      of volume-sensitive chloride channels in human cervical cancer HT-3 cells.
AB  - 1. The present study was carried out to identify the specific protein kinase C
      (PKC) isoform involved in regulatory volume decrease (RVD) responses, and to
      investigate the signal transduction pathways underlying the activation of volume
      sensitive chloride channels in human cervical cancer HT-3 cells. The role of Ca2+
      in RVD and in the activation of chloride currents was also studied. 2. The time
      course of RVDs was prolonged by microinjection of PKC-alpha antibody but not by
      PKC-beta or PKC-gamma antibody, and also by exposure to Ca2+-free medium, in
      particular when combined with microinjection of EDTA. Immunofluorescence staining
      showed that hypotonic superfusion evoked the translocation of PKC-alpha to the
      cell membrane, whereas PKC-beta or PKC-gamma remained unaffected. The
      translocation of PKC-alpha was observed a few minutes after hypotonic stress,
      reaching peak intensity at 30 min, and returned to the cytoplasm 60 min after
      hypotonic exposure. Western blot analyses showed an increased PKC-alpha level in
      terms of intensity and phosphorylation in the cell membrane, while neither PKC
      beta nor PKC-gamma was activated upon hyposmotic challenge. 3. Whole-cell patch
      clamp studies demonstrated that neomycin and PKC blockers such as staurosporine
      and H7 inhibited volume-sensitive chloride currents. The inhibitory effect of
      neomycin on chloride currents can be reversed by the PKC activator phorbol 12
      myristate, 13-acetate (PMA). Moreover, the PKC inhibitor and PKC-alpha antibody,
      but not PKC-beta or PKC-gamma antibody, significantly attenuated the chloride
      currents. The activation of volume-sensitive chloride currents were insensitive
      to the changes of intracellular Ca2+ but required the presence of extracellular
      Ca2+. 4. Our results suggest the involvement of PKC-alpha and extracellular Ca2+
      in RVD responses and the activation of volume-sensitive chloride channels in HT-3
      cells.

PMID- 9763634
TI  - Sodium pump evokes high density pump currents in rat midbrain dopamine neurons.
AB  - 1. Patch pipettes contained various concentrations of Na+ ([Na+]pip) in order to
      record strophanthidin-sensitive currents under voltage clamp in dopamine neurons
      in slices of rat substantia nigra and ventral tegmental area. 2. When [Na+]pip
      was 40 mM and the external K+ concentration ([K+]o) was 2.5 mM, strophanthidin
      (10 microM) evoked 461 +/- 121 pA of inward current. This effect was
      concentration dependent, with an EC50 of 7.1 +/- 2.6 microM. At potentials of -60
      to -120 mV, strophanthidin-induced currents were not associated with significant
      changes in chord conductance. 3. Strophanthidin (10 microM) evoked 234 +/- 43 pA
      of inward current when [Na+]pip was 0.6 mM, and 513 +/- 77 pA when [Na+]pip was
      80 mM. Despite higher pump currents with greater [Na+]pip, the strophanthidin
      EC50 was not significantly different for any of six different [Na+]pip. 4. Sodium
      pump currents were half-maximal when the [Na+]pip was about 1.3 mM. Maximum pump
      current was estimated at 830 pA (29 microA cm-2) at concentrations of
      intracellular Na+ that were assumed to be saturating (50-100 mM). 5.
      Strophanthidin currents were smaller in a reduced [K+]o (EC50 = 0.2 mM). 6. These
      data show that intracellular Na+ loading evokes relatively large pump currents.
      Our results are consistent with the physiological role of the sodium pump in
      burst firing in midbrain dopamine neurons

PMID- 9763635
TI  - Acid/base transport across the leech giant glial cell membrane at low external
      bicarbonate concentration.
AB  - 1. We have studied acid/base transport across the cell membrane of the giant
      neuropile glial cell in the leech (Hirudo medicinalis) central nervous system
      induced by changing the external pH (pHo), using double-barrelled, pH-sensitive
      microelectrodes. In the presence of 5 % CO2 and 24 mM HCO3-, the intracellular pH
      (pHi) rapidly changes due to a potent, reversible Na+-HCO3- cotransport across
      the glial membrane. We have now investigated the transport mechanism which leads
      to pHi changes in the nominal absence of CO2/HCO3-, where the HCO3- concentration
      is expected to be below 1 mM. 2. The intracellular pH increased and then
      decreased when pHo was altered from 7.4 to 7.8 and then 7.0 with a rate of
      increase of +0.026 +/- 0.008 and a rate of decrease of -0.028 +/- 0.009 pH units
      min-1 (+/- s.d., n = 49), indicating an acid/base flux rate of 0.64 and 0.71 mM
      min-1 across the glial membrane, respectively. 3. In the absence of external
      sodium (Na+replaced by N-methyl-D-glucamine), pHi slowly decreased, and the rate
      of alkali and acid loading was reduced to 19 and 28 %, respectively, (n = 12).
      Amiloride (2 mM), which inhibits Na+-H+ exchange, had no effect on the
      alkali/acid loading (n = 6). 4. The alkali and acid loading were not impaired
      after the removal of external chloride (Cl-o, replaced by gluconate; n = 11), but
      were significantly reduced by the anion transport inhibitor 4,4'
      diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS, 0.5 mM) to 23 and 16 %,
      respectively, of the control (P < 0.001; n = 5). 5. Alkali and acid loading were
      affected differently by manipulating the availability of residual HCO3-. After
      adding the membrane-permeable carbonic anhydrase inhibitor ethoxyzolamide (EZA, 2
      microM) to the saline, the acid loading, but not the alkali loading, was
      significantly reduced (by 25 %, P < 0.01), while lowering the residual CO2/HCO3-
      concentration in the saline by O2 bubbling significantly reduced the alkali
      loading (by 59 %, P < 0. 02), but not the acid loading. 6. Changing the membrane
      holding potential in voltage-clamped glial cells or raising the external K+
      concentration to 30 mM had no significant effect on acid/base loading. 7. It is
      concluded that a residual HCO3- concentration of less than 1 mM in nominally
      CO2/HCO3--free salines and HCO3- produced endogenously in the glial cells support
      alkali and acid loading across the glial cell membrane, presumably by activation
      of the reversible Na+-HCO3- cotransporter. The results suggest a very high
      selectivity and affinity of this cotransporter for HCO3-; they imply that HCO3-
      dependent processes may not be negligible even in the nominal absence of CO2/HCO3
      , when the HCO3- concentration is expected to be in the submillimolar range.

PMID- 9763637
TI  - Integrin and cytoskeletal involvement in signalling cell volume changes to
      glutamine transport in rat skeletal muscle.
AB  - 1. Muscle glutamine transport is modulated in response to changes in cell volume
      by a mechanism dependent on active phosphatidylinositol 3-kinase. We investigated
      the possibility that this mechanism requires interactions between the
      extracellular matrix (ECM), integrins and the cytoskeleton as components of a
      mechanochemical transduction system. 2. Using skeletal muscle cells, we studied
      effects of (a) inactivating integrin-substratum interactions by using integrin
      binding peptide GRGDTP with inactive peptide GRGESP as control, and (b)
      disrupting the cytoskeleton using colchicine or cytochalasin D, on glutamine
      transport after brief exposure to hypo-osmotic, isosmotic or hyperosmotic medium
      (170, 300 and 430 mosmol kg-1, respectively). 3. Neither GRGDTP nor GRGESP
      significantly affected basal glutamine uptake (0.05 mM; 338 +/- 58 pmol min-1 (mg
      protein)-1) but GRGDTP specifically prevented the increase (71%) and decrease
      (39%) in glutamine uptake in response to hypo- and hyperosmotic exposure,
      respectively. 4. Colchicine and cytochalasin D prevented the increase and
      decrease in glutamine uptake in response to changes in external osmolality. They
      also increased basal glutamine uptake by 59 +/- 19 and 85 +/- 16%, respectively,
      in a wortmannin-sensitive manner. 5. These results indicate involvement of ECM
      integrin-mediated cell adhesion and the cytoskeleton in mechanochemical
      transduction of cell volume changes to chemical signals modulating glutamine
      transport in skeletal muscle. Phosphatidylinositol 3-kinase may function to
      maintain the mechanotransducer in an active state.

PMID- 9763636
TI  - Regulated anion secretion in cultured epithelia from Sertoli cells of immature
      rats.
AB  - 1. Cultured epithelia of Sertoli cells from prepubertal rats were grown on
      Matrigel-coated millipore filters for short-circuit current (Isc) measurements.
      Under basal conditions, these epithelia exhibited a 'zero' transepithelial
      potential difference, a 'zero' short-circuit current and a transepithelial
      resistance of 60 Omega cm2. 2. Forskolin (100 microM) and 8-(4-chlorophenylthio)
      cAMP (cpt-cAMP) (100 microM) added to the apical side stimulated the Isc
      (forskolin, peak DeltaIsc = 1.32 +/- 0.16 microA cm-1; cpt-cAMP, peak DeltaIsc =
      0.88 +/- 0.16 microA cm-2). 3. ATP (100 microM) added apically elicited a Isc
      response (peak DeltaIsc = 6.45 +/- 0. 28 microA cm-2) which was similar in
      magnitude to that of 1 microM thapsigargin (peak DeltaIsc = 6.09 +/- 0.44 microA
      cm-2). The potency of the responses to other nucleotides: UTP >= ATP > ADP >> AMP
      = adenosine indicates the involvement of a mixture of P2Y receptors. 4. Removal
      of extracellular Cl- and HCO3- reduced the Isc response to ATP by 70 % and 40 %,
      respectively. Removal of K+ had no effect, whereas removal of Na+ attenuated the
      Isc response. 5. The response to ATP was insensitive to agents known to block
      anion secretion (except apical diphenylamine-2-carboxylate (DPC) and DIDS). The
      resistance to perturbation by pharmacological agents may be a unique property of
      the seminiferous epithelium. 6. Whole-cell current recordings in cultured rat
      Sertoli cells demonstrated a DIDS-sensitive outwardly rectifying Cl- conductance
      with activating and inactivating characteristics at depolarizing and
      hyperpolarizing voltages, respectively. 7. The stimulation of electrogenic ion
      transport by ATP may be part of a complex mechanism regulating fluid secretion by
      the testis. Cultured Sertoli cell epithelia are shown to provide a useful model
      to investigate transepithelial transport in the seminiferous epithelium.

PMID- 9763638
TI  - Effects of noradrenaline on intracellular pH in acutely dissociated adult rat
      hippocampal CA1 neurones.
AB  - 1. We examined the effects of noradrenaline on steady-state intracellular pH
      (pHi) and the recovery of pHi from internal acid loads imposed by the NH4+
      prepulse technique in hippocampal CA1 neurones acutely dissociated from adult
      rats. 2. Under nominally HCO3--free conditions, acid extrusion was accomplished
      by a Na+-dependent mechanism, probably the amiloride-insensitive variant of the
      Na+-H+ exchanger previously characterized in both fetal and adult rat hippocampal
      neurones. In the presence of external HCO3-, acid extrusion appeared to be
      supplemented by a Na+-dependent HCO3--Cl- exchanger, the activity of which was
      dependent upon the absolute level of pHi. 3. Noradrenaline evoked a concentration
      dependent and sustained rise in steady-state pHi and increased rates of pHi
      recovery from imposed intracellular acid loads. The effects of noradrenaline were
      not dependent upon the presence of external HCO3- but were blocked by
      substituting external Na+ with N-methyl-D-glucamine, suggesting that
      noradrenaline acts to increase steady-state pHi by increasing the activity of the
      Na+-H+ exchanger. 4. The effects of noradrenaline on steady-state pHi and on
      rates of pHi recovery from imposed acid loads were mimicked by beta1- and beta2-,
      but not alpha-, adrenoceptor agonists. The beta-adrenoceptor antagonist
      propranolol blocked the ability of noradrenaline to increase both steady-state
      pHi and rates of pHi recovery from acid loads. 5. The effects of noradrenaline on
      steady-state pHi and on pHi recovery rates following acid loads were not
      dependent on changes in [Ca2+]i. However, the effects of noradrenaline were
      blocked by pre-treatment with the adenylate cyclase inhibitor 2',5'
      dideoxyadenosine and the cAMP-dependent protein kinase inhibitors Rp-adenosine
      3',5'-cyclic monophosphorothioate (sodium salt; Rp-cAMPS) and N-[2-(p
      bromocinnamylamino)ethyl]-5-isoquinolinesulphonamide (H-89). 6. Forskolin, an
      activator of endogenous adenylate cyclase, and 3-isobutyl-1-methylxanthine, a
      phosphodiesterase inhibitor, mimicked the ability of noradrenaline to increase
      both steady-state pHi and rates of pHi recovery from imposed acid loads, as did
      Sp-cAMPS, a selective activator of cAMP-dependent protein kinase. The effect of
      forskolin on steady-state pHi was blocked by pre-treatment with Rp-cAMPS whereas
      the effect of Sp-cAMPS was enhanced by pre-treatment with the protein phosphatase
      inhibitor, okadaic acid. 7. Noradrenaline also increased steady-state pHi and
      rates of pHi recovery from imposed acid loads in cultured postnatal rat
      hippocampal neurones. In this preparation, the effects of noradrenaline were
      occluded by 18-24 h pre-treatment with cholera toxin. 8. We conclude that
      noradrenaline increases the activity of the Na+-H+ exchanger in rat hippocampal
      neurones, probably by inducing an alkaline shift in the pHi dependence of the
      antiport, thereby raising steady-state pHi. The effects of noradrenaline are
      mediated by beta-adrenoceptors via a pathway which involves the alpha-subunit of
      the stimulatory G-protein Gs (Gsalpha), adenylate cyclase, cAMP and the
      subsequent activation of cAMP-dependent protein kinase which, in turn, may
      phosphorylate the exchange mechanism.

PMID- 9763639
TI  - New observations on coupling between group II muscle afferents and feline gamma
      motoneurones.
AB  - 1. Extra- or intracellular recordings were made from seventy-six gamma
      motoneurones of hindlimb muscles in chloralose anaesthetized cats to re-assess
      the coupling between secondary muscle spindle afferents (group II muscle
      afferents) and these neurones. The latencies of a number of responses evoked by
      group II muscle afferents in gamma-motoneurones were shorter than minimal
      latencies of responses induced disynaptically in other spinal neurones. These
      latencies are therefore compatible with monosynaptic coupling between muscle
      spindle secondaries and gamma-motoneurones. 2. Responses fulfilling criteria for
      monosynaptically evoked responses were seen in about one third of gamma
      motoneurones with input from the group II muscle afferents tested (in 6 of 18
      motoneurones recorded intracellularly and in 26 of 74 motoneurones recorded
      extracellularly). They were usually evoked from only one of the stimulated
      nerves, stimulation of group II afferents of other nerves being followed by
      responses at longer latencies. 3. Most gamma-motoneurones were excited by group
      II afferents from several muscles, both flexors and extensors. However, a
      comparison of group II input to gamma-motoneurones innervating medial
      gastrocnemius and four other hindlimb muscles revealed differences in both
      incidence and sources. 4. This study extends results of previous studies by
      providing evidence that some synaptic actions of group II afferents, including
      afferents from the same muscle, are evoked monosynaptically, and may assist in
      sustaining the activation of gamma-motoneurones by positive feedback.

PMID- 9763640
TI  - Modulation of responses of feline gamma-motoneurones by noradrenaline, tizanidine
      and clonidine.
AB  - 1. Effects of noradrenaline (NA) and the alpha2 agonists tizanidine and clonidine
      were tested on extracellularly recorded responses of gamma-motoneurones in deeply
      anaesthetized cats. Two types of responses were used; firstly, short latency
      phasic responses evoked by electrical stimulation of group II afferents in a
      muscle nerve and, secondly, tonic background discharges. 2. Responses evoked by
      group II muscle afferents were depressed when NA and tizanidine were applied
      ionophoretically close to a gamma-motoneurone and when clonidine was applied
      systemically. The number of spike potentials evoked by stimulation of these
      afferents decreased and their latencies increased. Responses evoked by flexor or
      extensor afferents in gamma-motoneurones innervating flexors or extensors were
      similarly depressed. 3. Tonic discharges were inconsistently and/or
      insignificantly affected by locally applied NA and tizanidine but were depressed
      by systemically applied clonidine. 4. Control tests indicate specific effects of
      NA and tizanidine application since similarly ionophoresed H+ ions did not change
      responses of gamma-motoneurones to stimulation of group II afferents, or only
      weakly enhanced their background discharges. Furthermore, serotonin ejected from
      a solution with a similar pH facilitated rather than depressed responses of gamma
      motoneurones. 5. The results indicate that some antispastic effects of clonidine
      and tizanidine may be due to the depression of group II-evoked responses of gamma
      motoneurones, resulting in weaker responses of muscle spindles to muscle
      stretches.

PMID- 9763641
TI  - Reappearance of activity in the vestibular neurones of labyrinthectomized guinea
      pigs is not delayed by cycloheximide.
AB  - 1. In mammals, unilateral labyrinthectomy induces an immediate depression of the
      resting discharges in the neurones of the ipsilateral vestibular nuclei. Later
      on, a spontaneous restoration of this activity occurs. The aim of the present
      study was to test the possibility that protein synthesis could be involved in the
      start of this process in the guinea-pig. 2. Cycloheximide (CHX), a protein
      synthesis inhibitor, was injected intramuscularly 1 h before (30 mg kg-1) and 5 h
      after (15 mg kg-1) labyrinthectomy. 3. In a first group of animals, CHX was found
      to induce an inhibition of protein synthesis at levels ranging from 71 to 93% for
      9 h after labyrinthectomy. 4. In a second group of alert animals, we studied
      single unit activity of second-order vestibular neurones. It was found that, in
      the 12-16 h post-labyrinthectomy period, at a time when restoration began in
      guinea-pigs not treated with CHX, the discharges in the labyrinthectomized group
      treated with CHX were not different from those observed in a previous study in
      labyrinthectomized animals not treated with CHX. 5. We conclude that protein
      synthesis is not required for the start of restoration of activity in the
      vestibular neurones deprived of their ipsilateral labyrinthine input.

PMID- 9763642
TI  - Premature bifurcation of the apical dendritic trunk of vibrissa-responding
      pyramidal neurones of X-irradiated rat neocortex.
AB  - 1. Electrophysiological and morphological experiments were performed on the
      pyramidal neurones of the somatosensory neocortex of the adult rat that had been
      exposed in utero to 200 rad of X-irradiation. Under urethane anaesthesia, evoked
      gross potentials, extracellular and intracellular neuronal responses, and laminar
      field potentials were recorded. The evoked epicortical potential to deflection of
      a single whisker was a long-lasting positive wave which contrasted with a
      biphasic positive-negative complex in unirradiated controls. Neurones were
      initially tested during extracellular recording for responses to whisker
      deflections. This was followed by intracellular injection with horseradish
      peroxidase (HRP), and the HRP-stained neuronal elements were visualized using
      diaminobenzidine as a chromagen. 2. Fifty neurones were recorded and stained
      through the soma. The mean response latency was 15.1 ms. Of these, thirty-six
      showed premature bifurcation of the apical dendrite. The angle of bifurcation of
      the apical dendrite was measured in the coronal plane and was found to be a
      function of the depth at which the soma was located and the distance between the
      soma and bifurcation point. It was suggested that the apical dendrites of these
      neurones underwent premature bifurcation due to an imbalance between the growth
      of neurones and skull. 3. Fifteen neurones were recorded and stained through the
      presumed apical dendritic shaft. The mean response latency was 19.5 ms. The
      electrode track left in the histological specimen pointed to the stained apical
      dendrite. Dendritic elements distal to the entry point were preferentially filled
      with HRP. In no cases were somata stained. There was, in turn, no evidence of
      recording from dendritic elements distal to the bifurcation since no electrode
      track was found to point to these elements. That dendritic spike responses may
      not travel beyond the bifurcation was further substantiated by laminar analysis
      of field potentials.

PMID- 9763643
TI  - Modification of activity-dependent increases of cerebral blood flow by excitatory
      synaptic activity and spikes in rat cerebellar cortex.
AB  - 1. Mechanisms of activity-dependent increases in cerebral blood flow (CBF) were
      examined in rat cerebellar cortex using the laser Doppler flow technique and
      extracellular recordings of single unit activity and field potentials. 2.
      Stimulation of the monosynaptic climbing fibre system evoked long-lasting complex
      spikes in Purkinje cells, and extracellular field potentials with a
      characteristic profile that indicated contributions from both passive and active
      membrane mechanisms. The concomitant CBF increases were reproducible at fairly
      short intervals, and suggest that both synaptic activity and spikes may
      contribute to increased CBF. 3. Stimulation of the disynaptic parallel fibre
      system inhibited the spiking activity in Purkinje cells, while the postsynaptic
      activity increased as indicated by the simultaneously recorded field potential.
      Nevertheless, CBF always increased. The inhibition of spike firing activity was
      partly dependent on GABAergic transmission, but may also relate to the intrinsic
      membrane properties of Purkinje cells. 4. The CBF increases evoked by parallel or
      climbing fibre stimulation were highly correlated to the sum of neural
      activities, i.e. the negativity of field potentials multiplied by the stimulus
      frequency. This suggests a robust link between extracellular current flow and
      activity-dependent increases in CBF. 5. AMPA receptor blockade attenuated CBF
      increases and field potential amplitudes, while NMDA receptor antagonism did not.
      This is consistent with the idea that the CBF responses are of neuronal origin.
      6. This study has shown that activity-dependent CBF increases evoked by
      stimulation of cerebellar parallel fibres are dependent on synaptic excitation,
      including excitation of inhibitory interneurones, whereas the net activity of
      Purkinje cells, the principal neurones of the cerebellar cortex, is unimportant
      for the vascular response. For the climbing fibre system, not only synaptic
      activity but also the generation of complex spikes from Purkinje cells contribute
      to the increases in CBF. The strong correlation between CBF and field potential
      amplitudes suggests that extracellular ion fluxes contribute to the coupling of
      brain activity to blood flow.

PMID- 9763644
TI  - The influence of nerves on the secretion of immunoglobulin A into submandibular
      saliva in rats.
AB  - 1. The influence of sympathetic and parasympathetic nerve stimulations on
      salivary secretion of immunoglobulin A (IgA) was studied in the submandibular
      glands of anaesthetized rats by stimulating the nerve supplies with bipolar
      electrodes. 2. Although the flow of saliva from sympathetically stimulated glands
      was only 23% of that from parasympathetically stimulated glands the output of IgA
      was over 2-fold greater. This difference was attributable to influences of the
      nerves on IgA secretion through the epithelial cell polymeric immunoglobulin
      receptor-mediated pathway, as Western blotting with specific antibodies to IgA
      and secretory component revealed that secretory IgA (SIgA) dominated in all
      saliva samples. 3. Study of saliva secreted in sequential periods of nerve
      stimulation or following rest pauses suggested that SIgA secretion occurred in
      the absence of stimulation but this was upregulated 2.6- and 6-fold by
      parasympathetic and sympathetic nerve stimulations, respectively, compared with
      the calculated unstimulated rate. 4. The IgA content of extensively stimulated
      glands was 77% of levels in unstimulated contralateral control glands despite a
      secretion into saliva equivalent to almost 90% of the glandular IgA content. The
      IgA may be synthesized and secreted by glandular plasma cells at a rate which
      exceeds demand and/or such synthesis may be upregulated by nerve impulses. 5. The
      results indicate that salivary secretion of SIgA is upregulated by nerve impulses
      and that sympathetic nerves induce a greater effect than parasympathetic nerves.

PMID- 9763645
TI  - Necessity of acetylcholine for retinal directionally selective responses to
      drifting gratings in rabbit.
AB  - 1. A model for retinal directional selectivity postulates that GABAergic
      inhibition of responses to motions in the null (anti-preferred) direction
      underlies this selectivity. An alternative model postulates that besides this
      inhibition, there exists an asymmetric, nicotinic acetylcholine (ACh) input from
      starburst amacrine cells. It is possible for the latter but not the former model
      that stimuli could exist such that nicotinic blockade eliminates directional
      selectivity. Such stimuli would drive the cholinergic but not the GABAergic
      system well. 2. So far, attempts to eliminate directional selectivity with
      nicotinic blockade have failed, but they always used isolated, moving bars as the
      stimulus. We confirmed this failure for On-Off directionally selective (DS)
      ganglion cells in our preparation of the rabbit's retina. 3. However, while
      recording from these cells, we discovered that nicotinic blockade eliminated
      directional selectivity to drifting, low spatial frequency sine- and square-wave
      gratings. 4. This effect was not just due to the smallness of the responses under
      nicotinic blockade. NMDA blockade caused even smaller responses, but no loss of
      directional selectivity. 5. This result is consistent with a two-asymmetric
      pathways model of directional selectivity, but inconsistent with an asymmetric
      GABA-only model. 6. We conclude that asymmetric nicotinic inputs extend the range
      of stimuli that can elicit directional selectivity to include moving textures,
      that is, those with multiple peaks in their spatial luminance profile.

PMID- 9763646
TI  - Buffering of blood pressure variability by the renin-angiotensin system in the
      conscious dog.
AB  - 1. The renin-angiotensin system (RAS) participates in the compensation of major
      blood pressure disturbances such as haemorrhage and is involved in the tonic long
      term (> 1 day) maintenance of mean arterial blood pressure (MABP). Since its
      contribution to the short-term (< 1 h) buffering of normal blood pressure
      variability is not known, this was investigated in resting conscious dogs. 2. The
      regulatory efficiency and the response time of the RAS were studied by an acute
      step reduction of renal artery pressure to 70 mmHg for 1 h using a suprarenal
      aortic cuff. After a delay of at least 100 s, MABP rose exponentially by 22 +/- 5
      mmHg in normal dogs (n = 4), by 6 +/- 3 mmHg after angiotensin converting enzyme
      (ACE) inhibition (n = 4), and by 25 +/- 5 mmHg after ganglionic blockade (n = 4).
      MABP returned to control after release of the cuff with similar time courses. The
      time constants of the MABP responses were in the range of 20 min. Thus, possible
      feedback oscillations of the RAS would be expected around 0.0025 Hz (1/(4 x 100
      s)); a buffering effect would be possible below this frequency. 3. Blood pressure
      variability was investigated by spectral analysis of MABP from 3.75 h recordings
      in the frequency ranges of 0.002-0.003 Hz (feedback oscillations) and below 0.002
      Hz (buffering effect). 4. ACE inhibition (n = 7) decreased MABP by 11 +/- 2 mmHg
      (P < 0.05), but in both frequency ranges integrated spectral density was not
      affected. ACE inhibition also failed to significantly change spectral density in
      either of the two frequency ranges under the following conditions: (1) during
      ganglionic blockade (n = 7), (2) during a low-sodium diet (except for a very
      slight elevation below 0.002 Hz) (n = 7), and (3) when the fall of MABP induced
      by ACE inhibition was compensated by an angiotensin II infusion (n = 7). 5. It is
      concluded that in spite of its high regulatory efficiency with an adequate
      response time the RAS does not directly contribute to the short-term buffering of
      blood pressure variability, nor does it give rise to feedback oscillations under
      normal resting conditions. Even if the RAS is stimulated by sodium restriction
      its contribution to short-term blood pressure buffering is only marginal.

PMID- 9763648
TI  - In vivo measurements of the triceps surae complex architecture in man:
      implications for muscle function.
AB  - 1. The objectives of this study were to (1) quantify experimentally in vivo
      changes in pennation angle, fibre length and muscle thickness in the triceps
      surae complex in man in response to changes in ankle position and isometric
      plantarflexion moment and (2) compare changes in the above muscle architectural
      characteristics occurring in the transition from rest to a given isometric
      plantarflexion intensity with the estimations of a planimetric muscle model
      assuming constant thickness and straight muscle fibres. 2. The gastrocnemius
      medialis (GM), gastrocnemius lateralis (GL) and soleus (SOL) muscles of six males
      were scanned with ultrasonography at different sites along and across the muscle
      belly at rest and during maximum voluntary contraction (MVC) trials at ankle
      angles of -15 deg (dorsiflexed direction), 0 deg (neutral position), +15 deg
      (plantarflexed direction) and +30 deg. Additional images were taken at 80, 60, 40
      and 20% of MVC at an ankle angle of 0 deg. 3. In all three muscles and all
      scanned sites, as ankle angle increased from -15 to +30 deg, pennation increased
      (by 6-12 deg, 39-67%, P < 0.01 at rest and 9-16 deg, 29-43%, P < 0.01 during MVC)
      and fibre length decreased (by 15-28 mm, 32-34%, P < 0.01 at rest and 8-10 mm, 27
      30%, P < 0.05 during MVC). Thickness in GL and SOL increased during MVC compared
      with rest (by 5-7 mm, 36-47%, P < 0.01 in GL and 6-7 mm, 38-47%, P < 0.01 in SOL)
      while thickness of GM did not differ (P > 0.05) between rest and MVC. 4. At any
      given ankle angle the model underestimated changes in GL and SOL occurring in the
      transition from rest to MVC in pennation angle (by 9-12 deg, 24-38%, P < 0.01 in
      GL and 9-14 deg, 25-28%, P < 0.01 in SOL) and fibre length (by 6-15 mm, 22-39%, P
      < 0.01 in GL and 6-8 mm, 23-24%, P < 0.01 in SOL). 5. The findings of the study
      indicate that the mechanical output of muscle as estimated by the model used may
      be unrealistic due to errors in estimating the changes in muscle architecture
      during contraction compared with rest.

PMID- 9763647
TI  - Voluntary activation of human elbow flexor muscles during maximal concentric
      contractions.
AB  - 1. To measure voluntary activation of human elbow flexor muscles during maximal
      concentric contractions, the twitch interpolation method was modified to enable
      detection of torque increments evoked by single stimuli during contractions of up
      to 300 deg s-1. Subjects flexed the elbow to rotate a loaded beam 'as fast as
      possible' (load typically 23-58 N m) from 70 deg below to 70 deg above the
      horizontal. Electrical stimuli were delivered to biceps brachii when the beam
      passed through the horizontal. Voluntary activation was estimated from the
      amplitude of the interpolated twitch, which was expressed as a percentage of the
      twitch produced by relaxed muscles shortening at the same velocity. 2. In eleven
      subjects, the level of voluntary activation during repeated maximal concentric
      contractions (median 99.4%) did not differ significantly from that during maximal
      isometric contractions (98.0%). Voluntary activation during maximal contractions
      did not depend on shortening velocity and was the same when tested at two angles
      30 deg apart. 3. To induce fatigue, five subjects repeatedly lifted and lowered a
      heavy load at about 30 deg s-1, and continued for ten to twelve contractions
      after they needed assistance to continue lifting. All maintained the capacity to
      attain maximal levels of activation. 4. It is concluded that voluntary drive to
      elbow flexor muscles during maximal concentric contractions is usually maximal or
      near-maximal, and that this level of drive can be maintained during development
      of peripheral fatigue.

PMID- 9763649
TI  - Damage to human muscle from eccentric exercise after training with concentric
      exercise.
AB  - 1. It is known that a period of eccentric exercise provides protection against
      damage to muscle from subsequent eccentric exercise. Here we ask, does concentric
      exercise do the opposite, make muscle more prone to damage? 2. The triceps surae
      muscle group of one leg in each of eight human subjects was subjected to 30 min
      of concentric exercise per day, for 5 days. At the end of the training period
      there was a small but significant increase in passive torque in the exercised
      muscle (P < 0.05), with no changes in the untrained muscle. 3. After a single
      period of eccentric exercise, angle-torque curves for muscles of both legs
      shifted in the direction of longer muscle lengths, suggestive of an increase in
      series compliance. The shift in the concentrically trained muscle was
      significantly greater over the first 48 h post-exercise (P < 0. 05). 4. The
      volume of the trained leg increased significantly more than the untrained leg for
      five subjects over 72 h post-exercise (P < 0.05). Peak torque fell, passive
      stiffness increased and both muscles became sore, but with no significant
      differences between the two legs. 5. It is concluded that a period of concentric
      exercise increases the susceptibility of muscle to changes associated with the
      damage from eccentric exercise.

PMID- 9763650
TI  - Habituation of the initial responses to cold water immersion in humans: a central
      or peripheral mechanism?
AB  - 1. The initial respiratory and cardiac responses to cold water immersion are
      thought to be responsible for a significant number of open water deaths each
      year. Previous research has demonstrated that the magnitude of these responses
      can be reduced by repeated immersions in cold waterwhether the site of
      habituation is central or peripheral. 2. Two groups of subjects undertook two 3
      min head-out immersions in stirred water at 10 C of the right-hand side of the
      body (R). Between these two immersions (3 whole days) the control group (n = 7)
      were not exposed to cold water, but the habituation group (n = 8) undertook a
      further six 3 min head-out immersions in stirred water at 10 C of the left-hand
      side of the body (L). 3. Repeated L immersions reduced (P < 0.01) the heart rate,
      respiratory frequency and volume responses. During the second R immersion a
      reduction (P < 0.05) in the magnitude of the responses evoked was seen in the
      habituation group but not in the control group, despite both groups having
      identical skin temperature profiles. 4. It is concluded that the mechanisms
      involved in producing habituation of the initial responses are located more
      centrally than the peripheral receptors.

PMID- 9763651
TI  - Report of the seventh international workshop on human chromosome 21 mapping 1997.

PMID- 9763652
TI  - The cytogenetic and molecular characterization of benign and malignant soft
      tissue tumors.
AB  - Cytogenetic analyses of benign and malignant soft tissue tumors have led to the
      description of recurrent, specific, and even pathognomonic chromosomal
      translocations and/or other rearrangements in most types of soft tissue tumors.
      The consistent karyotypic rearrangements have provided critical diagnostic
      information in this group of neoplasms that often presents significant diagnostic
      challenges to the clinician and the pathologist. These findings have also been
      instrumental in the characterization of the abnormalities at the molecular level.
      Novel genes have been isolated from the translocation junctions and the
      mechanisms of their deregulation identified. This has increased our understanding
      of the histogenesis of these tumors, paved the way for the molecular diagnosis of
      many sarcomas, aided in directing therapy, and also provided important prognostic
      information.

PMID- 9763653
TI  - Assignment of protein kinase C eta (Pkch) to mouse chromosome band 12C3-D2 by in
      situ hybridization.

PMID- 9763654
TI  - Assignment of IkappaB kinase beta (IKBKB) to human chromosome band 8p12-->p11 by
      in situ hybridization.

PMID- 9763655
TI  - Assignment of the human oxidized low-density lipoprotein receptor gene (OLR1) to
      chromosome 12p13.1-->p12.3, and identification of a polymorphic CA-repeat marker
      in the OLR1 gene.

PMID- 9763656
TI  - Genomic organization of the bovine aromatase encoding gene and a homologous
      pseudogene as revealed by DNA fiber FISH.
AB  - In cattle, the CYP19 locus comprises the aromatase cytochrome P450-encoding gene
      (CYP19) and a homologous pseudogene (CYP19P1). It has been assigned to chromosome
      region 10q26. Cloning of genomic DNA revealed that the CYP19 gene covers more
      than 56 kb. Its precise extent is still unknown because the DNA spanning the
      untranslated first exon 1.1 and the coding region (exons 2 to 10) have not been
      isolated. Furthermore, the chromosome arrangement of closely linked CYP19 and
      CYP19P1 was also not clear. To establish a high resolution physical map of the
      entire CYP19 locus, fluorescence in situ hybridization to extended bovine genomic
      DNA fibers (fiber FISH) was performed. The results demonstrate (1) that the clone
      containing exon 1.1 is located about 19 kb upstream from the CYP19 coding region.
      (2) Within the chromosome region 10q26 CYP19 and CYP19P1 are arranged "tail-to
      head", being separated by a distance of about 24 kb between the labeled clones.
      (3) The physical size of the bovine CYP19 locus amounts to a minimum of 130 kb.

PMID- 9763657
TI  - Cloning of TCFL5 encoding a novel human basic helix-loop-helix motif protein that
      is specifically expressed in primary spermatocytes at the pachytene stage.
AB  - We have isolated a novel human gene that is expressed specifically in primary
      spermatocytes in the testis. The cDNA contains an open reading frame of 1356 bp,
      encoding a 452-amino-acid protein that includes a basic Helix-Loop-Helix (bHLH)
      motif. The gene, which was mapped to chromosome region 20q13.3-->qter by
      fluorescence in situ hybridization, consists of six exons and spans approximately
      24 kb of genomic DNA. Immunohistochemical staining located the gene product
      exclusively in cell nuclei of primary spermatocytes at the pachytene stage, but
      not in those at the leptonema stage. We named this gene TCFL5 (transcription
      factor-like 5, basic helix-loop-helix). The cell-type and stage-specific
      expression of TCFL5 indicates that this protein may function in a crucial role in
      spermatogenesis as a transcription factor by regulating cell proliferation or
      differentiation of cells through binding to a specific DNA sequence like other
      bHLH molecules.

PMID- 9763658
TI  - Linkage mapping of Lims1l, the murine homolog of the human LIM domain gene PINCH,
      to mouse chromosome 10.
AB  - The human LIM domain gene LIMS1 was used to identify a mouse homolog. The
      resulting mouse sequence was used to identify a polymorphism by SSCP analysis.
      Linkage studies performed in the EUCIB backcross placed Lims1l on the proximal
      portion of mouse Chromosome 10. This localisation makes it an interesting
      candidate for the deafness mutant, waltzer (v).

PMID- 9763659
TI  - Hemizygous deletion of the HPC-1/syntaxin 1A gene (STX1A) in patients with
      Williams syndrome.
AB  - HPC-1/syntaxin 1A is a membrane protein that plays an important role in
      exocytosis of neurotransmitters from neuronal cells. We previously mapped the
      human HPC-1/syntaxin 1A gene (STX1A) to chromosome 7q11.2, which is within the
      Williams syndrome (WS) region. Here, we performed FISH analysis on 46 patients
      with WS to examine the relationship between STX1A and WS. Our results showed a
      hemizygous deletion of the HPC-1/syntaxin 1A gene in each patient, suggesting
      that the neurological symptoms of WS may be related to the hemizygous deletion of
      STX1A.

PMID- 9763660
TI  - Pathogenetics of 45,X/46,XY gonadal mosaicism.
AB  - Five patients with 45,X/46,XY mosaicism ranging from 8% to 66% of 46, XY
      lymphocytes in the peripheral blood were studied. Their age when chromosome
      studies were performed ranged from a few days to 37 yr. The phenotypic
      presentations were two females with gonadal dysgenesis and Turner syndrome
      features (cases 1 and 2), two males with ambiguous genitalia and mixed gonadal
      dysgenesis (cases 3 and 4), and an infertile male with an atrophic testis (case
      5). Fluorescence in situ hybridization (FISH) using dual-color X and Y probes on
      paraffin-embedded sections of the gonads was performed to assess mosaicism. A
      mosaic cell line with a Y chromosome was present in the streak ovary, dysgenetic
      gonad, and testis. In the mixed gonadal dysgenesis cases (cases 3 and 4), the
      testis had a higher percentage (greater than two fold) of XY cells than the ovary
      had. However, the highest ratio of cells with a Y chromosome was in the atrophic
      testis of the infertile male (case 5). The distribution of mosaic clones in the
      different gonadal cell types was examined. Both females (cases 1 and 2) with
      dysgenetic gonads had scant ovarian stroma and nests of Leydig or hilus cells. In
      FISH studies, the coelomic epithelial cells were predominantly 46,XY; in
      comparison, the Leydig and hilus cells had a lower percentage and the ovarian
      stroma the least number of cells with a Y signal. A mixed gonadal dysgenesis case
      (case 3) possessed a right testis with an XY complement in approximately 21% of
      Sertoli cells and approximately 14% of Leydig cells. The infertile male had an
      atrophic testis with interstitial hyperplasia (case 5). His testis contained
      Sertoli cells but no evidence of spermatogenesis. FISH detected a Y signal in
      about 50-60% of the Sertoli and Leydig cells.

PMID- 9763661
TI  - Position effect of translocations involving the inactive X chromosome: physical
      linkage to XIC/XIST does not lead to long-range de novo inactivation in human
      differentiated cells.
AB  - Given the reported long-range cis-inactivating effect of the XIST gene in early
      embryonic development and the lack of requirement of X-chromosome-specific
      elements for propagating the inactive state, there exists the possibility of cis
      inactivation of autosomal material after de novo translocation to an inactive X
      chromosome (Xi) in differentiated cells. We have analyzed de novo radiation
      induced translocations between the Xi and autosomes to study the maintenance and
      spreading of X-chromosome inactivation (X inactivation) in relation to the
      position of the X-inactivation center (XIC)/XIST in differentiated cells.
      Autosome/Xi translocations were detected by fluorescence in situ hybridization
      (FISH). The activation status of the chromosomes involved in the translocation
      was determined by simultaneous immunocytogenetic studies using antibodies against
      either BrdU incorporated at late S phase or acetylated histone H4. The position
      of XIC/XIST in the reciprocal products of the translocation was determined by
      XIST-specific FISH and computer enhancement. In other experiments, the Xq13
      region carrying XIC/XIST was localized by computer enhancement of the DAPI
      banding pattern. Our study in differentiated cells provides a visual
      demonstration that physical separation from XIC/XIST does not result in
      reactivation of inactive X-chromosome material and that X inactivation is not
      spread to the translocated autosomes irrespective of the position of XIC/XIST.
      This observation suggests that physical linkage to XIC/XIST does not lead to de
      novo inactivation of autosomal material.

PMID- 9763662
TI  - Genetic mapping of mouse centromere protein (Incenp and Cenpe) genes.
AB  - Inner centromere protein (INCENP) and centromere protein E (CENPE) are two
      functionally important proteins of the higher eukaryotic centromere. Using a
      mouse Incenp genomic DNA and a mouse Cenpe cDNA to analyze recombinant inbred
      mouse sets, as well as interspecific backcross panels, we have mapped these genes
      to the proximal regions of mouse Chromosomes 19 and 6, respectively. Comparison
      of Cenpe and human CENPE, which maps to chromosome region 4q24-->q25, has further
      identified a new region of homology between the two species.

PMID- 9763663
TI  - Localization of FCGR1 encoding Fcgamma receptor class I in primates: molecular
      evidence for two pericentric inversions during the evolution of human chromosome
      1.
AB  - The human high-affinity receptor for immunoglobulin G, FcgammaRI (FCGR1), is
      encoded by a family of three genes that share over 95% sequence homology.
      Curiously, the three genes in this recently duplicated gene family flank the
      centromere of human chromosome 1, with FCGR1B located at 1p12 and both FCGR1A and
      FCGR1C located at 1q21. We have previously speculated that a pericentric
      inversion could account for the separation of the genes in the FCGR1 family and
      explain their current chromosomal location. Here we present evidence, obtained
      through fluorescence in situ hybridization analysis, that in the rhesus monkey
      (Macaca mulatta) and baboon (Papio papio) FCGR1 is located adjacent to the
      centromere on the chromosomal arm with greatest homology to human 1p, whereas in
      the chimpanzee (Pan troglodytes) it is located adjacent to the centromere on the
      chromosomal arm with greatest homology to human 1q. The separation of the FCGR1
      gene family in humans suggests that the location of a second pericentric
      inversion, known to distinguish the human from the chimpanzee chromosome 1, is
      within the FCGR1 gene family. This finding refines the assignment of homology
      between the human and chimpanzee chromosomes 1.

PMID- 9763664
TI  - Analysis of chromosome aberrations in a mammary carcinoma cell line from a dog by
      using canine painting probes.
AB  - A cell line derived from a spleen metastasis of a mammary carcinoma in a female
      dog was analyzed by fluorescence in situ hybridization with canine chromosome
      specific paints. The cell line showed a modal chromosome number of 77, with three
      (90% of the cells) or four (10% of the cells) biarmed chromosomes. Aberrations
      observed relate to chromosomes 8 or 11, 13 or 15, 37, 38, and X and include
      chromosome loss (X), formation of isochromosomes (8 or 11, 13 or 15), and centric
      fusion (37 and 38). In all aberrations, whole chromosomes are involved. None of
      the genes known to be related to breast cancer development in humans and that has
      mapped in the dog is located on one of the aberrant chromosomes. The results of
      this study show that chromosome painting is a most useful tool for the analysis
      of canine tumor cells.

PMID- 9763665
TI  - A baboon (Papio hamadryas) with an isochromosome for the long arm of the X.
AB  - A 5.5-yr-old female baboon was evaluated for sexual immaturity. She was small for
      her age and had normal external female genitalia. However, she lacked cyclical
      perineal turgescence and displayed atypical coloration of the perineal skin.
      Laparoscopy revealed a small uterus and absence of both ovaries. Cytogenetic
      analysis revealed a 42,X,i(X)(q10) karyotype. DNA analysis using loci DXS1683,
      which maps to Xp22.1, and DXS297, which maps to Xq27.3, was consistent with
      inheritance of the normal X chromosome from the dam and formation of the
      isochromosome Xq from the paternal X.

PMID- 9763666
TI  - Baboon/human homologies examined by spectral karyotyping (SKY): a visual
      comparison.
AB  - Baboon (Papio hamadryas) metaphase chromosomes were analyzed using spectral
      karyotyping (SKY), a technique combining fluorescence microscopy, CCD-imaging,
      and Fourier spectroscopy. Results from a comparison of SKY analyses using probes
      derived from human chromosomes on baboon metaphases were consistent with the
      majority of comparative gene mapping data between the two species. These data
      were also compatible with earlier studies comparing macaque and human
      chromosomes. Human (HSA) chromosome 2 was homologous to baboon (PHA) chromosomes
      12 (HSA 2q) and 13 (HSA 2p), whereas three baboon chromosomes corresponded to two
      different human chromosomes: PHA 3 to HSA 7 and HSA 21, PHA 7 to HSA 14 and HSA
      15, and PHA 10 to HSA 20 and HSA 22. These results support the retained synteny
      between the Hominidae and Cercopithecidae genomes.

PMID- 9763667
TI  - Structure and chromosome mapping of the human small maf-genes MAFG and MAFK.
AB  - The newly emerged Maf family proteins possess a highly conserved basic leucine
      zipper (bZip) domain in common and are subdivided into large and small Maf
      proteins. The Maf family proteins appear to regulate cell differentiation
      processes and also cellular functions as partner molecules of CNC family
      proteins. To facilitate understanding of the function of small Maf proteins, we
      isolated the genes (MAFG and MAFK) encoding human small Maf proteins MafG and
      MafK and characterized their structures and organization by means of restriction
      enzyme mapping, Southern blot hybridization and nucleotide sequence analysis.
      Organization of the small maf genes are highly conserved in vertebrates,
      suggesting an important functional contribution of the gene products. We also
      examined the location of these genes within the human genome by fluorescence in
      situ hybridization (FISH) analysis. Human MAFG and MAFK are located at 17q25 and
      7p22, respectively. Thus, small maf genes are not clustered in a single locus.

PMID- 9763668
TI  - Assignment of CASP8 to human chromosome band 2q33-->q34 and Casp8 to the murine
      syntenic region on chromosome 1B-proximal C by in situ hybridization.

PMID- 9763669
TI  - Assignment of the melanocortin 4 receptor (MC4R) gene to human chromosome band
      18q22 by in situ hybridisation and radiation hybrid mapping.

PMID- 9763670
TI  - Assignment of the E1A-regulated transcription factor E4F gene (E4F1) to human
      chromosome band 16p13.3 by in situ hybridization and somatic cell hybrids.

PMID- 9763671
TI  - Genomic structure of a novel human gene (XYLB) on chromosome 3p22-->p21.3
      encoding a xylulokinase-like protein.
AB  - We isolated a novel human cDNA of 1963 nucleotides that included an open reading
      frame encoding a protein of 528 amino acids. Homology analysis indicated that the
      predicted gene product, XYLB, bore 22% identity to the xylulokinase of
      Haemophilus influenzae that plays an important role in energy metabolism. The
      gene consists of 18 exons and spans about 28 kb of genomic DNA on chromosome
      3p21.3.

PMID- 9763673
TI  - Fine mapping of 12 previously unassigned EST clones to individual YACs in the
      familial Alzheimer's disease (FAD) region of chromosome 14q24.3.
AB  - We have constructed an approximately 4-Mb YAC contig spanning the microsatellite
      markers D14S1028-D14S61 on chromosome 14q24.3 using oligonucleotide primers to
      microsatellite markers, ESTs and the genes PSEN1, FOS, TGFB3 and UBE2L1. This
      contig consists of 44 ICI YACs and 5 megaCEPH YACs. The data reported here should
      aid the final construction of an integrated map of chromosome 14 and allow the
      identification and accurate mapping of additional novel ESTs within this region.

PMID- 9763672
TI  - Assignment of the IkappaB-beta gene NFKBIB to human chromosome band 19q13.1 by in
      situ hybridization.

PMID- 9763674
TI  - Assignment of the horse progesterone receptor (PGR) and estrogen receptor (ESR1)
      genes to horse chromosomes 7 and 31, respectively, by in situ hybridization.

PMID- 9763675
TI  - Assignment of the horse mitochondrial glutamate oxaloacetate transaminase 2
      (GOT2) and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) to
      horse chromosome 3 by in situ hybridization.

PMID- 9763676
TI  - Mapping of the NDUFA2, NDUFA6, NDUFA7, NDUFB8, and NDUFS8 electron transport
      chain genes by intron based radiation hybrid mapping.

PMID- 9763677
TI  - Intron based radiation hybrid mapping of 15 complex I genes of the human electron
      transport chain.
AB  - At least 34 complex I subunits of the electron transport chain are encoded by the
      nuclear genome, but only 14 of these have been mapped in the human. To rapidly
      map additional subunits, we have performed a combination of database mining and
      direct "wet" experimentation to identify intron and/or 5' upstream genomic DNA
      regions for 16 complex I genes. Wet experimentation was applied to 5 genes, and
      involved direct PCR amplification of introns by inter-exon PCR or splinkerette
      based PCR walking. Database mining was applied to 11 genes, and entailed the
      identification of incompletely spliced mRNAs and genomic CpG island clone
      sequences. This data was in files that carried no documentary description of the
      non-exon regions. Non-exon sequences were thus derived for 15 complex I genes and
      used to design functional gene specific PCR assays. Radiation hybrid mapping of
      these PCRs located 15 complex I genes to chromosomes l, 4, 5 (2 genes), 7 (2
      genes), 8, 9 (2 genes), 11, 14, 16 (2 genes), 18, and 19.

PMID- 9763678
TI  - Assignment of candidate DNA methyltransferase gene (DNMT2) to human chromosome
      band 10p15.1 by in situ hybridization.

PMID- 9763679
TI  - Assignment of FRA1H common fragile site to human chromosome band 1q42.1 proximal
      to the nuclear NAD+ ADP-ribosyltransferase gene (ADPRT) and to the main 5S rRNA
      gene locus.

PMID- 9763680
TI  - Chromosomal localization of the human cytoplasmic dynein heavy chain gene DNCH2
      to 11q21-->q22.1.

PMID- 9763681
TI  - Autosomal-dominant, prelingual, nonprogressive sensorineural hearing loss:
      localization of the gene (DFNA8) to chromosome 11q by linkage in an Austrian
      family.
AB  - A four-generation family suffering from an autosomal-dominant, congenital,
      nonprogressive, nonsyndromic hearing loss was found in a rural region of Austria.
      The hearing loss was moderate to severe, a pure tone audiogram showing a U-shaped
      form with maximum loss at 2, 000 Hz. An initial genome search led to a lod score
      of 3.01 with markers on chromosome 15. This locus was registered as DFNA8 in the
      HUGO data base. Further sampling of the family, however, yielded data that
      reduced the maximal lod score with chromosome 15 markers to 1.81. The genome
      search was restarted using an ABITM genotyper, which eventually detected several
      positive two-point lod scores with markers from the long arm of chromosome 11.
      The highest value was 3. 6, which was seen with the marker D11S934. Haplotype
      analysis excluded the gene from the chromosomal region proximal from D11S898 and
      distal to D11S1309. These results place the gene in the region of the hearing
      loss gene DFNA12. Recent evidence suggests that the somewhat different phenotypes
      found in these two families are due to two different mutations in the human alpha
      tectorine gene (Verhoeven et al., 1998).

PMID- 9763682
TI  - Abstracts of the 35th american cytogenetics conference 

PMID- 9763683
TI  - Xanthan gum biosynthesis and application: a biochemical/genetic perspective.
AB  - Xanthan gum is a complex exopolysaccharide produced by the plant-pathogenic
      bacterium Xanthomonas campestris pv. campestris. It consists of D-glucosyl, D
      mannosyl, and D-glucuronyl acid residues in a molar ratio of 2:2:1 and variable
      proportions of O-acetyl and pyruvyl residues. Because of its physical properties,
      it is widely used as a thickener or viscosifier in both food and non-food
      industries. Xanthan gum is also used as a stabilizer for a wide variety of
      suspensions, emulsions, and foams. This article outlines aspects of the
      biochemical assembly and genetic loci involved in its biosynthesis, including the
      synthesis of the sugar nucleotide substrates, the building and decoration of the
      pentasaccharide subunit, and the polymerization and secretion of the polymer. An
      overview of the applications and industrial production of xanthan is also
      covered.

PMID- 9763688
TI  - Bacterial complementation as a means to test enzyme-ligand interactions.
AB  - A bacterial complementation assay has been developed for the rapid screening of a
      large number of compounds to identify those that inhibit an enzyme target for
      structure-based inhibitor design. The target enzyme is the hypoxanthine
      phosphoribosyltransferase (HPRT). This enzyme has been proposed as a potential
      target for inhibitors that may be developed into drugs for the treatment of
      diseases caused by several parasites. The screening assay utilizes genetically
      deficient bacteria complemented by active, recombinant enzyme grown in selective
      medium in microtiter plates. By comparing absorbance measurements of bacteria
      grown in the presence and absence of test compounds, the effect of the compounds
      on bacterial growth can be rapidly assayed. IC50 values for inhibition of
      bacterial growth are a reflection of the ability of the compounds to bind and/or
      inhibit the recombinant enzyme. We have tested this bacterial complementation
      screening assay using recombinant HPRT from the parasites. Plasmodium falciparum
      and Trypanosoma cruzi, as well as the human enzyme. The results of these studies
      demonstrate that a screening assay using bacterial complement selection can be
      used to identify compounds that target enzymes and can become an important part
      of structure-based drug design efforts.

PMID- 9763687
TI  - Characterization of a novel Streptococcus thermophilus rolling-circle plasmid
      used for vector construction.
AB  - The complete nucleotide sequence of pER371, a native plasmid in Streptococcus
      thermophilus ST137, was determined. A putative open reading frame coding for a
      replication protein, Rep371, was identified. A characteristic promoter sequence
      and ribosome-binding site were found upstream of rep371. Rep371 (247 amino acid
      residues) does not show homology with RepA and RepS of the small S. thermophilus
      cryptic plasmids pST1-No.29 and pST1 respectively. The plus-origin sequence and
      Rep371 are highly homologous to the corresponding elements of the Staphylococcus
      aureus plasmids pC194 and pSK89. A novel 140-nucleotide palindromic minusorigin
      sequence, which is structurally similar but does not show sequence homology to
      the palA region of pC194, was identified in pER371. A palindromic sequence
      capable of forming a putative hairpin structure was identified and subsequently
      recognized as being highly conserved among several lactococcal rolling-circle
      plasmids. Cloning vectors derived from pER371 should provide valuable gene
      delivery vehicles for the genetic engineering of lactic acid bacteria.

PMID- 9763689
TI  - Efficient production of intact human parathyroid hormone in a Saccharomyces
      cerevisiae mutant deficient in yeast aspartic protease 3 (YAP3).
AB  - When human parathyroid hormone (hPTH) is expressed as a secretory product in
      yeast, the main problem is the aberrant proteolytic cleavage that reduces the
      yield of intact protein. To overcome this problem, we developed an hPTH
      expression system using a host strain in which the YAP3 gene encoding yeast
      aspartic protease 3 (YAP3) was disrupted. After 48 h of culture, most of the hPTH
      secreted by the yap3 disruptant remained intact, whereas more than 90% of the
      hPTH secreted by the wild-type strain was cleaved. When the authentic hPTH was
      incubated in each of the culture supernatants of untransformed yap3 disruptant
      and wild-type strain, the proteolysis proceeded much more slowly in the culture
      supernatant of yap3 disruptant than in that of the wild type. The extent of hPTH
      proteolysis was also significantly reduced by the addition of pepstatin A, a
      specific aspartic protease inhibitor. The results suggest that YAP3 is involved
      in the internal cleavage of hPTH expressed in yeast. The correct processing of
      the intact hPTH secreted in the yap3 disruptant demonstrates that the yeast
      mutant lacking the YAP3 activity is a suitable host for the high-level expression
      of intact hPTH.

PMID- 9763691
TI  - Composition of the cell walls of several yeast species.
AB  - Cell walls, representing 26%-32% of the cell dry weight, were prepared from
      several strains of the yeasts Kloeckera apiculata, Debaryomyces hansenii,
      Zygosaccharomyces bailii, Kluyveromyces marxianus and Saccharomyces cerevisiae.
      Extraction of the walls with potassium hydroxide at 4 degrees C, followed by
      saturation of the alkali-soluble extract with ammonium sulphate gave fractions of
      mannoprotein, alkali-soluble glucan and alkali-insoluble glucan. Chitin was
      associated with the alkali-insoluble glucan. The proportions of the different
      fractions within the walls varied with the species and strain. Mannoprotein
      comprised between 25% and 34% of the walls, the content of alkali-insoluble
      glucan ranged from 15% to 48%, and the content of alkali-soluble glucan ranged
      from 10% to 48%. There was significant variation in the physical appearance of
      the alkali-soluble glucans and the relative viscosity of suspensions of these
      glucans. The yeasts could represent novel sources of polysaccharides with
      industrial and medical applications.

PMID- 9763690
TI  - Production of trehalose synthase from a basidiomycete, Grifola frondosa, in
      Escherichia coli.
AB  - The genomic DNA and cDNA for a gene encoding a novel trehalose synthase (TSase)
      catalyzing trehalose synthesis from alpha-D-glucose 1-phosphate and D-glucose
      were cloned from a basidiomycete, Grifola frondosa. Nucleotide sequencing showed
      that the 732-amino-acid TSase-encoding region was separated by eight introns.
      Consistent with the novelty of TSase, there were no homologous proteins
      registered in the data-bases. Recombinant TSase with a histidine tag at the NH2
      terminal end, produced in Escherichia coli, showed enzyme activity similar to
      that purified from the original G. frondosa strain. Incubation of alpha-D-glucose
      1-phosphate and D-glucose in the presence of recombinant TSase generated
      trehalose, in agreement with the enzymatic property of TSase that the equilibrium
      lay far in the direction of trehalose synthesis.

PMID- 9763692
TI  - The colonization of a simulator of the human intestinal microbial ecosystem by a
      probiotic strain fed on a fermented oat bran product: effects on the
      gastrointestinal microbiota.
AB  - The effects of Lactobacillus-GG-fermented oat bran product on the microbiota and
      its metabolic activity in the human gut were investigated, using a simulator of
      the human intestinal microbial ecosystem (SHIME), by analysing the bacterial
      population, shortchain fatty acids and gas production. In addition, the effects
      of fermented oat bran supernatant and supernatant samples from reactors 4, 5 and
      6 (large intestine) on the growth of Escherichia coli IHE 13047, Enterococcus
      faecalis VTT E-93203, Lactobacillus rhamnosus VTT E-94522 (Lactobacillus GG) and
      Lactococcus lactis subsp. lactis VTT E-90414 were monitored to ascertain possible
      stimulatory/inhibitory effects by an in vitro turbidometric method. Our
      experiments showed that Lactobacillus GG colonized the SHIME reactor and this
      colonization could be maintained for several weeks without extra supplementation.
      Oat bran feeding also favoured the growth of bifidobacteria and caused an
      increase in the production of acetic, propionic and butyric acid as well as CH4
      and CO2. However, the effects of oat bran, either on bacterial populations or on
      their metabolic activity, were not directly dose-dependent. In turbidometric
      measurements, the supernatant of fermented oat bran exerted an inhibitory effect
      of Lactobacillus GG, but stimulated the growth of enterococci.

PMID- 9763694
TI  - Detection of ferulic acid esterase production by Bacillus spp. and lactobacilli.
AB  - The production of feruloyl esterase activity by Bacillus spp. and lactobacilli
      can be detected in an agarplate assay. The assay involves the substitution of the
      main carbon source in specific agar with ethyl ferulate. A number of Bacillus
      spp., predominantly B. subtilis strains, were found to exhibit feruloyl esterase
      activity by this method. Of the examined lactobacilli, Lb. fermentum (NCFB 1751)
      showed the highest level of ferulic acid esterase activity. The enzyme was
      released from harvested cells by sonication and showed pH and temperature optima
      of 6.5 and 30 degrees C respectively.

PMID- 9763693
TI  - Antimould activity of sourdough lactic acid bacteria: identification of a mixture
      of organic acids produced by Lactobacillus sanfrancisco CB1.
AB  - Sourdough lactic acid bacteria, cultivated in wheat flour hydrolysate, produced
      antimould compounds. The antimould activity varied greatly among the strains and
      was mainly detected within obligately heterofermentative Lactobacillus spp. Among
      these, Lb. sanfrancisco CB1 had the largest spectrum. It inhibited moulds related
      to bread spoilage such as Fusarium, Penicillium, Aspergillus and Monilia. A
      mixture of acetic, caproic, formic, propionic, butyric and n-valeric acids,
      acting in a synergistic way, was responsible for the antimould activity. Caproic
      acid played a key role in inhibiting mould growth.

PMID- 9763695
TI  - The use of Escherichia coli bearing a phoN gene for the removal of uranium and
      nickel from aqueous flows.
AB  - A Citrobacter sp. originally isolated from metal-polluted soil accumulates heavy
      metals via metalphosphate deposition utilizing inorganic phosphate liberated via
      PhoN phosphatase activity. Further strain development was limited by the non
      transformability of this environmental isolate. Recombinant Escherichia coli DH5
      alpha bearing cloned phoN or the related phoC acquired metal-accumulating
      ability, which was compared with that of the Citrobacter sp. with respect to
      removal of uranyl ion (UO2(2+)) from dilute aqueous flows and its deposition in
      the form of polycrystalline hydrogen uranyl phosphate (HUO2PO4). Subsequently,
      HUO2PO4-laden cells removed Ni2+ from dilute aqueous flows via intercalation of
      Ni2+ into the HUO2PO4 lattice. Despite comparable acid phosphatase activity in
      all three strains, the E. coli DH5 alpha (phoN) construct was superior to
      Citrobacter N14 in both uranyl and nickel accumulation, while the E. coli DH5
      alpha (phoC) construct was greatly inferior in both respects. Expression of
      phosphatase activity alone is not the only factor that permits efficient and
      prolonged metal phosphate accumulation, and the data highlight possible
      differences in the PhoN and PhoC phosphatases, which are otherwise considered to
      be related in many respects.

PMID- 9763696
TI  - Virus removal from bioproducts using ultrafiltration membranes modified with
      latex particle pretreatment.
AB  - Ultrafiltration is an attractive process for virus removal from bioproducts owing
      to its high throughput as well as the fact that the operation is carried out
      under ambient conditions (damage to proteins is highly limited). The principal
      concern regarding the adoption of conventional ultrafiltration membranes for
      virus removal is the possibility of the virus passing through abnormally large
      pores or surface imperfections on the membrane surface. The chief principle
      behind the present work is to pretreat the membrane by blocking the abnormally
      large pores using latex particles. Experimental work was conducted to validate
      this pretreatment using the bacteriophage phi x 174 as a model virus. The results
      attained were highly encouraging. Different sizes of latex particles were tested
      by treating a 100 KD molecular weight cut-off membrane, and the transmission of
      phage (suspended in buffer) through this membrane assessed. In the absence of any
      particle pretreatment, a virus clearance of 4.78 log reduction value was observed
      for this membrane. The transmission of phage through the membrane could be
      reduced by an order of magnitude using 0.11 micron latex particles, or two orders
      of magnitude using a combination of 0.11 and 0.50 micron particles. The
      application of latex particles did not hinder the transport of protein through
      the 100 KD membrane. Protein sieving coefficients obtained using this membrane
      were 91%, 16% and 2%, for lysozyme, HSA and IgG, respectively.

PMID- 9763698
TI  - Weak affinity chromatography of small saccharides with immobilised wheat germ
      agglutinin and its application to monitoring of carbohydrate transferase
      activity.
AB  - In this work we have evaluated the potential to use wheat germ agglutinin (WGA)
      for weak affinity chromatography (WAC) of N-acetyl derivatives of mono-, di-, tri
      and tetrasaccharides. WGA was used as a ligand in a high performance liquid
      affinity chromatography (HPLAC) system. Isocratic affinity chromatography was
      conducted where similar N-acetyl saccharides were separated according to their
      binding strength to WGA. Affinities are weak and lie typically in the mM range.
      For example, for 3'sialyllactose, the dissociation constant (Kd) was found to be
      2.4 mM at 8 degrees C. It was interesting to note that the WGA-HPLC column can
      distinguish between the anomeric forms of N-acetylglucosamine. Weak affinity
      chromatography with immobilised WGA was used in an enzyme assay to detect the
      activity of GlcNAc-transferases.

PMID- 9763699
TI  - Ribose-5-phosphate isomerase from Saccharomyces cerevisiae: purification and
      molecular analysis of the enzyme.
AB  - Purification and molecular analysis of ribose-5-phosphate isomerase (EC 5.3.1.6)
      from Saccharomyces cerevisiae is described first time. The enzyme was enriched
      from a haploid deletion mutant containing the wild-type gene on a multicopy
      plasmid elaborating the following steps: ammonium sulphate precipitation,
      interfacial salting out on Sepharose 6B, high performance liquid chromatography
      on Fractogel EMD DEAE and on Resource Phenyl. The enzyme activity was found to be
      rather unstable possibly caused by removal of stabilizing cofactors or proteins
      during the purification procedure. The purified enzyme showed a hyperbolic
      dependence on the substrate ribose-5-phosphate with a K(m)-value of 1.6 +/- 0.3
      mmol/l. For the native enzyme a molecular mass of 115 +/- 10 kDa was determined
      as found by saccharose density gradient centrifugation, sedimentation equilibrium
      analysis, size exclusion chromatography and polyacrylamide gel electrophoresis.
      Sodium dodecyl sulphate polyacrylamide gel electrophoresis and Western blotting
      revealed one band with a molecular mass of 31 +/- 2 kDa. Thus, the native enzyme
      is composed of four subunits of identical size. The molecular mass of the subunit
      and the identified N-terminal sequence of 33 amino acids fits well the 258 amino
      acid protein encoded by the S. cerevisiae RKI open reading frame, which was
      characterized previously only by increasing specific activities of ribose-5
      phosphate isomerase in cells after cloning the gene. On the basis of the
      conserved amino acids an alignment of the amino acid sequence of ribose-5
      phosphate isomerase from yeast with those of the enzyme from mouse, spinach and
      Escherichia coli is presented.

PMID- 9763700
TI  - IgG and hybridoma partitioning in aqueous two-phase systems containing a dye
      ligand.
AB  - The effect of the important ATPS- and buffer parameters on IgG and hybridoma
      partitioning in ATPSs containing a PEG-dye-ligand was studied. Objective was to
      establish selection criteria for effective ligands for extractive fermentations
      with animal cells in ATPSs. In the presence of 1% PEG-dye-ligand the binding of
      IgG to the PEG-ligand was affected severely by the Na-chloride concentration. The
      tie-line length and pH affected IgG partitioning to a lesser extent. The desired
      partitioning of IgG into the top phase, was only obtained when, in addition to
      the 10 mmol/kg K-phosphate buffer, no Na-chloride was present. In an ATPS culture
      medium, with +/- 35 mmol/kg Na-bicarbonate and 60 mmol/kg Na-chloride, increasing
      the PEG-dye-ligand concentration up to 100% did increase the partition
      coefficient, but was not effective in concentrating the IgG in the top phase of
      ATPS culture medium at a pH of 7.8. Furthermore, addition of the PEG-dye-ligand
      to ATPS culture medium changed the hybridoma cell partitioning from the bottom
      phase to the interface.

PMID- 9763701
TI  - Segment-specific retention of a larval neuromuscular system and its role in a
      new, rhythmic, pupal motor pattern in Manduca sexta.
AB  - At pupation in Manduca sexta, accessory planta retractor muscles and their
      motoneurons degenerate in segment-specific patterns. Accessory planta retractor
      muscles in abdominal segments 2 and 3 survive in reduced form through the pupal
      stage and degenerate after adult emergence. Electromyographic and
      electrophysiological recordings show that these accessory planta retractor
      muscles participate in a new, rhythmic 'pupal motor pattern' in which all four
      muscles contract synchronously at approximately 4 s intervals for extended bouts.
      Accessory planta retractor muscle contractions are driven by synaptic activation
      of accessory planta retractor motoneurons and are often accompanied by rhythmic
      activity in intersegmental muscles and spiracular closer muscles. The pupal motor
      pattern is influenced by descending neural input although isolated abdominal
      ganglia can produce a pupal motor pattern-like rhythm. The robust pupal motor
      pattern first seen after pupal ecdysis weakens during the second half of pupal
      life. Anemometric recordings indicate that the intersegmental muscle and
      spiracular closer muscle component of the pupal motor pattern produces
      ventilation. Accessory planta retractor muscle contractions lift the flexible
      abdominal floor, to which the developing wings and legs adhere tightly. We
      hypothesize that, by a bellows-like action, the accessory planta retractor muscle
      contractions circulate hemolymph in the appendages. Morphometric analysis shows
      that dendritic regression is similar in accessory planta retractor motoneurons
      with different pupal fates, and that accessory planta retractor motoneurons begin
      to participate in the pupal motor pattern while their dendrites are regressed.

PMID- 9763702
TI  - Auditory role of the suprabranchial chamber in gourami fish.
AB  - Fish hearing specialists (e.g., goldfish, holocentrids, clupeoids, mormyrids)
      have evolved specialized structures (e.g., Weberian ossicles, swimbladder
      diverticulae, gas-filled bullae) to enhance their auditory frequency range and
      threshold sensitivity. The inner ears of anabantoid fish are encased in
      membranous cranial bones and are protruded into air-filled suprabranchial
      chambers. This research was intended to test the hypothesis that the gas bubbles
      inside the suprabranchial chambers may modulate the hearing abilities of
      anabantoid fish because of their proximity to the membranous bone-encased inner
      ears. Three species of gourami (blue gourami Trichogaster trichopterus; kissing
      gourami Helostoma temminckii; dwarf gourami Colisa lalia) were examined. Using
      the auditory brainstem response recording technique, baseline audiograms tested
      at 300, 500, 800, 1500, 2500, 4000 Hz were obtained. The air bubbles in the
      suprabranchial chambers were replaced by water, and the audiograms were
      remeasured. Thresholds were elevated in all three species. When three blue
      gouramis were allowed to replenish air into the suprabranchial chambers their
      hearing abilities returned to baseline levels. These results support the
      hypothesis that air bubbles in the suprabranchial chambers can affect hearing
      abilities of gouramis by lowering the thresholds.

PMID- 9763703
TI  - Dipole source localization by mottled sculpin. III. Orientation after site
      specific, unilateral denervation of the lateral line system.
AB  - To test the hypothesis that spatial excitation patterns along the lateral-line
      system underlie source localization, we videotaped the orientation behavior of
      blinded mottled sculpin in response to a small dipole source (50-Hz vibrating
      sphere) before and after unilateral denervation of the lateral line system on
      different body regions (head, trunk and head + trunk). Approach pathways were
      qualitatively similar to those followed by normal intact animals. Abnormal
      behavior (turning in circles) was not observed. However, the frequency with which
      fish placed their intact side facing the source increased by 12-89%, depending on
      the denervation site. The angular accuracy of orientation decreased by 20 degrees
      to 60 degrees (100% to 370% change) depending on source location and region of
      lateral line denervated. Deficits tended to be site-specific. For example,
      unilaterally denervating lateral-line organs on the head resulted in less
      accurate orienting responses when the source was located on the denervated side
      of the head, but not on the opposite side of the head or on either side of the
      trunk. Site-specific deficits and the absence of abnormal approach pathways argue
      that animals are relying on a point-by-point spatial representation of source
      location along the sensory surface rather than computations based on bilateral
      comparisons.

PMID- 9763704
TI  - Visual acuity, contrast sensitivity and retinal magnification in a marsupial, the
      tammar wallaby (Macropus eugenii).
AB  - The visual acuity of the tammar wallaby was estimated using a behavioural
      discrimination task. The wallabies were trained to discriminate a high-contrast
      (86%) square-wave grating from a grey field of equal luminance (1000-6000 cd m
      2). Visual-evoked cortical potentials were used to measure the complete contrast
      sensitivity function. The stimulus was a sinusoidal phase reversal of a
      sinusoidally modulated grating of various spatial frequencies and contrasts with
      a mean luminance of 40 cd m-2). The behavioural acuity was estimated to be about
      4.8 cycles/deg. The contrast sensitivity peaked at about 0.15 cycles/deg and
      declined towards both lower and higher spatial frequencies. The cut-off frequency
      of the contrast sensitivity function is slightly lower than the behaviourally
      measured acuity at about 2.7 cycles/deg. The retinal magnification factor was
      estimated anatomically from laser lesions to be about 0.16 mm/deg. Based on the
      known ganglion cell density and the retinal magnification factor, an anatomical
      upper limit to visual acuity of about 6 cycles/deg can be calculated. The
      differences in estimates of visual acuity between the behavioural and anatomical
      methods on the one side and physiology on the other side are discussed.

PMID- 9763705
TI  - Indole-3-acetic acid is synthesized from L-tryptophan in roots of Arabidopsis
      thaliana.
AB  - The promoter of the nit1 gene, encoding the predominantly expressed isoform of
      the Arabidopsis thaliana (L.) Heynh. nitrilase isoenzyme family, fused to the
      beta-glucuronidase gene (uidA) drives beta-glucuronidase expression in the root
      system of transgenic A. thaliana and tobacco plants. This expression pattern was
      shown to be controlled developmentally, suggesting that the early differentiation
      zone of root tips and the tissue surrounding the zone of lateral root primordia
      formation may constitute sites of auxin biosynthesis in plants. The root system
      of A. thaliana was shown to express functional nitrilase enzyme. When sterile
      roots were fed [2H]5-L-tryptophan, they converted this precursor to [2H]5-indole
      3-acetonitrile and [2H]5-indole-3-acetic acid. This latter metabolite was further
      metabolized into base-labile conjugates which were the predominant form of [2H]5
      indole-3-acetic acid extracted from roots. When [1-13C]-indole-3-acetonitrile was
      fed to sterile roots, it was converted to [1-13C]-indole-3-acetic acid which was
      further converted to conjugates. The results prove that the A. thaliana root
      system is an autonomous site of indole-3-acetic acid biosynthesis from L
      tryptophan.

PMID- 9763706
TI  - Sub-cellular immunolocalization of the glucosinolate sinigrin in seedlings of
      Brassica juncea.
AB  - Polyclonal rat antibodies were raised to a bovine serum albumin-sinigrin
      conjugate and used to immunolocalize sinigrin (2-propenylglucosinolate) in
      imbibed seeds and developing seedlings of Brassica juncea. (L.) Czern. Sinigrin
      was localized to protein bodies in aleurone-like cells but shown to be absent
      from myrosin cells. Double labelling techniques were used to co-localize both
      myrosinase (beta-thioglucoside glucohydrolase, EC 3.2.3.1) and sinigrin. Myrosin
      grains were labelled only with the anti-myrosinase antibody, but aleurone cells
      were labelled with both anti-myrosinase and anti-sinigrin antibodies. High
      performance liquid chromatographic analysis of conventionally fixed and
      dehydrated seed tissues (4 h post imbibition in water), indicated a high
      proportion of sinigrin was retained in fixed tissues. Over a time course of 100
      h, protein bodies within aleurone-like cells degraded, fused to form the cell
      vacuole and lost all myrosinase labelling but retained residual sinigrin
      labelling. The degradation of protein bodies corresponded to a decrease in
      retention of sinigrin in the fixed tissues. The results describe for the first
      time the co-localization of a plant enzyme and its substrate, a secondary
      metabolite.

PMID- 9763707
TI  - Effect of aluminum on cytoplasmic Ca2+ homeostasis in root hairs of Arabidopsis
      thaliana (L.).
AB  - Aluminum inhibition of root growth is a major world agricultural problem where
      the cause of toxicity has been linked to changes in cellular calcium homeostasis.
      Therefore, the effect of aluminum ions (Al) on changes in cytoplasmic free
      calcium concentration ([Ca2+]c) was followed in root hairs of wild-type, Al
      sensitive and Al-resistant mutants of Arabidopsis thaliana (L.) Heynh. Generally,
      Al exposure resulted in prolonged elevations in tip-localized [Ca2+]c in both
      wild-type and Al-sensitive root hairs. However, these Al-induced increases in
      [Ca2+]c were not tightly correlated with growth inhibition, occurring up to 15
      min after Al had induced growth to stop. Also, in 32% of root hairs examined
      growth stopped without a detectable change in [Ca2+]c. In contrast, Al-resistant
      mutants showed little growth inhibition in response to AlCl3 exposure and in no
      case was a change in [Ca2+]c observed. Of the other externally applied stresses
      tested (oxidative and mechanical stress), both were found to inhibit root hair
      growth, but only oxidative stress (H2O2, 10 microM) caused a prolonged rise in
      [Ca2+]c similar to that induced by Al. Again this increase occurred after growth
      had been inhibited. The lack of a tight correlation between Al exposure, growth
      inhibition and altered [Ca2+]c dynamics suggests that although exposure of root
      hairs to toxic levels of Al causes an alteration in cellular Ca2+ homeostasis,
      this may not be a required event for Al toxicity. The elevation in [Ca2+]c
      induced by Al also strongly suggests that the phytotoxic action of Al in root
      hairs is not through blockage of Ca2(+)-permeable channels required for Ca2+
      influx into the cytoplasm.

PMID- 9763708
TI  - Molecular cloning of the cDNA coding for the (R)-(+)-mandelonitrile lyase of
      Prunus amygdalus: temporal and spatial expression patterns in flowers and mature
      seeds.
AB  - A gene highly expressed in the floral organs of almond (Prunus amygdalus Batsch),
      and coding for the cyanogenic enzyme (R)-(+)-mandelonitrile lyase (EC 4.1.2.10),
      has been identified and the full-length cDNA sequenced. The temporal expression
      pattern in maturing seeds and during floral development was analyzed by RNA blot,
      and the highest mRNA levels were detected in floral tissues. The spatial mRNA
      accumulation pattern in almond flower buds was also analyzed by in-situ
      hybridization. The mRNA levels were compared during seed maturation and floral
      development in fruit and floral samples from cultivars classified as homozygous
      or heterozygous for the sweet-almond trait or homozygous for the bitter trait. No
      correlation was found between these characteristics and levels of mandelonitrile
      lyase mRNA, suggesting that the presence of this protein is not the limiting
      factor in the production of hydrogen cyanide.

PMID- 9763711
TI  - Purification of a nitrate reductase kinase from Spinacea oleracea leaves, and its
      identification as a calmodulin-domain protein kinase.
AB  - Spinach (Spinacea oleracea L.) nitrate reductase (NR) is inactivated by
      phosphorylation on serine-543, followed by binding of the phosphorylated enzyme
      to 14-3-3 proteins. We purified one of several chromatographically distinct
      NRserine-543 kinases from spinach leaf extracts, and established by Edman
      sequencing of 80 amino acid residues that it is a calcium-dependent (calmodulin
      domain) protein kinase (CDPK), with peptide sequences very similar to Arabidopsis
      CDPK6 (accession no. U20623; also known as CPK3). The spinach CDPK was recognized
      by antibodies raised against Arabidopsis CDPK. Nitrate reductase was
      phosphorylated at serine-543 by bacterially expressed His-tagged CDPK6, and the
      phosphorylated NR was inhibited by 14-3-3 proteins. However, the bacterially
      expressed CDPK6 had a specific activity approx. 200-fold lower than that of the
      purified spinach enzyme. The physiological control of NR by CDPK is discussed,
      and the regulatory properties of the purified CDPK are considered with reference
      to current models for reversible intramolecular binding of the calmodulin-like
      domain to the autoinhibitory junction of CDPKs.

PMID- 9763713
TI  - A cysteine endopeptidase with a C-terminal KDEL motif isolated from castor bean
      endosperm is a marker enzyme for the ricinosome, a putative lytic compartment.
AB  - A papain-type cysteine endopeptidase with a molecular mass of 35 kDa for the
      mature enzyme, was purified from germinating castor bean (Ricinus communis L.)
      endosperm by virtue of its capacity to process the glyoxysomal malate
      dehydrogenase precursor protein to the mature subunit in vitro (C. Gietl et al.,
      1997, Plant Physiol 113: 863-871). The cDNA clones from endosperm of germinating
      seedlings and from developing seeds were isolated and sequence analysis revealed
      that a very similar or identical peptidase is synthesised in both tissues.
      Sequencing established a presequence for co-translational targeting into the
      endoplasmic reticulum, an N-terminal propeptide and a C-terminal KDEL motif for
      the castor bean cysteine endopeptidase precursor. The 45-kDa pro-enzyme stably
      present in isolated organelles was enzymatically active. Immunocytochemistry with
      antibodies raised against the purified cysteine endopeptidase revealed highly
      specific labelling of ricinosomes, organelles which co-purify with glyoxysomes
      from germinating Ricinus endosperm. The cysteine endopeptidase from castor bean
      endosperm, which represents a senescing tissue, is homologous to cysteine
      endopeptidases from other senescing tissues such as the cotyledons of germinating
      mung bean (Vigna mungo) and vetch (Vicia sativa), the seed pods of maturing
      French bean (Phaseolus vulgaris) and the flowers of daylily (Hemerocallis sp.).

PMID- 9763714
TI  - Identification of sequence homology between the internal hydrophilic repeated
      motifs of group 1 late-embryogenesis-abundant proteins in plants and hydrophilic
      repeats of the general stress protein GsiB of Bacillus subtilis.
AB  - Late embryogenesis abundant (LEA) proteins are speculated to protect against
      water stress in plants. Group 1 LEA proteins are hydrophilic and vary mainly in
      the numbers of an extremely hydrophilic internal 20-amino-acid motif. This motif
      is present up to four times in Arabidopsis thaliana and Hordeum vulgare Group 1
      proteins and has been described in numerous plant species. However, no similarity
      has yet been described between Group 1 genes or gene products and those from non
      plant species. We report here the striking similarity between the repeated
      internal motif of Group 1 LEA proteins and a repeated hydrophilic motif present
      in a stress-related protein (GsiB) from Bacillus subtilis.

PMID- 9763716
TI  - [The 28th Western regional meeting and 28th Eastern regional meeting of the
      Japanese Society of Nephrology. 1998. Abstracts].

PMID- 9763715
TI  - [The 33rd conference of Japanese Medical Society of Alcohol and Drug Studies.
      August 28-30, 1998. Osaka, Japan. Abstracts].

PMID- 9763717
TI  - [40th Annual meeting of the Japan Geriatrics Society. Fukuoka, Japan. June 17-19,
      1998. Abstracts].

PMID- 9763718
TI  - Interventions to improve the use of antimalarials in south-east Asia: an
      overview.
AB  - There are few drugs for malaria, and those which are available for use are
      subject to rapid development of resistance. Curiously, little effort has been
      made to improve drug use in malaria-endemic countries and to assess the benefits
      of such improvements. Advances can be made in public understanding of the value
      of ingesting a full regimen of antimalarials, in order to achieve complete cure,
      and in improving simple technologies (blister packaging) to achieve the same
      result. Better efforts can be made to reduce the availability of fake or
      substandard drugs in the marketplace. In this article, we describe the outcome of
      a concerted effort to improve drug compliance and drug quality in an area of
      multidrug resistance for malaria. These research efforts, guided by the Task
      Force for Improved Use of Antimalarials, characterized the problems in drug
      compliance in South-East Asia, and developed interventions to improve drug use in
      the various countries. Interventions involved drug packaging, public information
      campaigns, and assessments of drug quality. Results show that blister packaging
      worked best to improve drug compliance and that the increased cost of packaged
      medication did not limit its use. Drug quality was a major problem in unregulated
      countries and should be improved.

PMID- 9763719
TI  - The effect of drug packaging on patients' compliance with treatment for
      Plasmodium vivax malaria in China.
AB  - A study conducted in 1994 showed that the use of blister packs containing
      antimalarial drugs significantly increased patients' compliance, compared with
      traditional means of dispensing drugs in a paper envelope. The present study
      assessed patients' compliance and compared the difference between 3-day
      chloroquine and 8-day primaquine courses of treatment for vivax malaria. The
      level of real compliance was determined by making the drugs with phenobarbital,
      and measuring its level in the blood following treatment. The results show that
      blister packaging significantly improved patients' compliance (p < 0.001) over
      traditional means of dispensing antimalarial drugs; there was no difference in
      treatment compliance between 3-day and 8-day courses when the drugs were in
      blister packs. However, with ordinary packaging the treatment compliance rate for
      an 8-day course was significantly less than for a 3-day course (P < 0.05).

PMID- 9763720
TI  - Childhood malaria in the Lao People's Democratic Republic.
AB  - The idea that malaria in South-East Asia is synonymous with adult malaria is
      questioned in this paper. In the Lao People's Democratic Republic, community
      based malariometric data were collected in Savannakhet Province, which shares
      borders with Viet Nam in the east and Thailand in the west. The data indicate
      that endemic malaria is rural and stable in large areas of the province. In these
      areas, which are rarely subject to malaria control, there is significant
      childhood malaria. A little more than one-quarter of individuals examined in mass
      blood surveys carried out in the peak malaria season were parasite-positive.
      Unlike other studies in the region reporting a declining risk of positive
      parasitaemia with age, thus suggesting immunity consistent with high and
      prolonged exposure to malaria, the communities studied in the Lao People's
      Democratic Republic did not show the expected acquisition of immunity. Further
      community-based studies on this matter are therefore warranted.

PMID- 9763721
TI  - Influence of blister packaging on the efficacy of artesunate + mefloquine over
      artesunate alone in community-based treatment of non-severe falciparum malaria in
      Myanmar.
AB  - Three studies were carried out to determine the need, acceptability, and efficacy
      of adding mefloquine to artemisinin derivatives (AD) for the first-line treatment
      of uncomplicated falciparum malaria. The first was a retrospective study of 255
      basic health workers which showed that their recommendation of AD to patients
      depended on their level of training. None of the paramedics/midwives and only 9%
      of 129 doctors had prescribed AD, and no one had recommended AD in combination
      with mefloquine; 72% of patients used courses that were too short for
      parasitological cure. To promote the addition of mefloquine to AD regimens we
      conducted intervention workshops with health care providers and subsidized the
      cost of mefloquine to patients. In the second study, we interviewed 200 patients
      before and after the intervention to evaluate drug compliance with full doses of
      AD and use of subsidized mefloquine. After the intervention, we found that only
      3.6% had used mefloquine and 62% had taken non-curative doses of AD. In the third
      study, we provided blister packs of medication in daily doses and compared the
      intake of AD + placebo (158 patients) with that of AD + mefloquine (222 patients)
      for 5 days. The compliance with both regimens was 99%. Blood smears for parasites
      on day 28 showed one positive in the AD + mefloquine group and 7 positive in the
      AD group. We conclude that provision of blister packs of daily doses is a very
      effective way to improve compliance with short courses and drug combinations, but
      the efficacy of the combination in Myanmar in this particular study was only
      marginally higher than that of AD alone.

PMID- 9763722
TI  - Improving compliance with quinine + tetracycline for treatment of malaria:
      evaluation of health education interventions in Cambodian villages.
AB  - To improve compliance with a 7-day quinine + tetracycline regimen against
      malaria, two health education interventions were tested on populations in two
      separate groups of villages. In one group, the use of posters and video improved
      the compliance rates from 0.5% to 20% (20% effectiveness; 95% confidence interval
      (CI), 13-26%); in the other, where posters alone were used, full compliance
      changed from 6% to 11% (6% effectiveness; 95% CI, 0-12%). The improved compliance
      in the first group occurred mainly among those who went to health practitioners
      (effectiveness 40%) rather than drug vendors (effectiveness 2%), although this
      could not be attributed to differences in the advice they gave to patients. After
      the poster plus video intervention, more patients bought quinine + tetracycline
      and received correct advice encouraging the use of a full course; however, not
      all of them actually completed the full course by self-administration.

PMID- 9763723
TI  - Use and quality of antimalarial drugs in the private sector in Viet Nam.
AB  - This study examines the use and quality of antimalarial drugs in the growing
      private sector of Viet Nam. The practices of drug vendors (called alternative
      treatment providers (ATPs)) as well as their stocks and the quality of drugs sold
      by them, and the local production and distribution of antimalarials were
      investigated. Antimalarials were sold by the vast majority of ATPs, almost all
      the common antimalarials being available for sale. The practices and indications
      for sale, however, varied. Underdosing for malaria was frequent in all three
      provinces studied, and lack of knowledge of the appropriate regimen for cure was
      common among the drug-sellers. Samples of antimalarials were collected from ATP
      outlets in the three provinces, and the drugs were assessed for their contents
      and expiry date by the Institute of Drug Quality Control in Hanoi. Of the 218
      samples of drugs examined by the Institute, over 96% met the quality
      requirements. However, a 10% sample of these drugs were independently assessed by
      WHO and revealed a different picture: 70% of them failed to meet the standard
      specifications required. There is therefore an urgent need to improve the
      capability and monitoring procedures of bodies involved in assessing and
      regulating drugs in Viet Nam.

PMID- 9763724
TI  - Compliance with artesunate and quinine + tetracycline treatment of uncomplicated
      falciparum malaria in Thailand.
AB  - A randomized, controlled, malaria-clinic-based field trial was conducted to
      compare compliance with a 7-day quinine + tetracycline regimen and a 5-day 700-mg
      artesunate regimen for the treatment of uncomplicated falciparum malaria in a
      community in Thailand. Of 137 patients, aged 15-60 years attending a malaria
      clinic, 77 received artesunate and 60 received quinine + tetracycline. Compliance
      and cure rates were evaluated on days 5 (artesunate) and 7 (quinine +
      tetracycline) using patient interview/residual pill counts and peripheral blood
      smear, respectively. Data were analysed using the intention-to-treat approach,
      and the reasons for compliance and noncompliance were investigated. Compliance
      was significantly higher (98.4%) with artesunate than with quinine + tetracycline
      (71.7%) (relative risk adjusted for sex (aRR) = 1.39 (95% C.I. = 1.15-1.68);
      referent: quinine + tetracycline). Cure rate (100%) was higher in those receiving
      artesunate than quinine + tetracycline (77.4%) (aRR = 1.32 (95% C.I. = 1.12
      1.55)). Reasons for compliance included the desire to be cured and to follow the
      advice of malaria staff/employer, and the simple dosing regimen. Noncompliance
      was mostly due to adverse reactions and forgetting to take the drugs. These
      results can serve as a baseline for designing and evaluating new interventions to
      improve compliance, as well as for studying cost-effectiveness to help drug
      policy decision-making. We recommend a strategy which integrates a short-course,
      once-a-day regimen (with minimal adverse reactions), a better delivery system for
      antimalarial drugs and health education, and an enhanced advisory role of malaria
      staff. Considering the higher compliance rate and curative effectiveness of
      artesunate, we recommend its use instead of quinine + tetracycline for the
      treatment of uncomplicated malaria in clinics in Thailand.

PMID- 9763725
TI  - Initial evaluation of low-dose phenobarbital as an indicator of compliance with
      antimalarial drug treatment.
AB  - Since poor compliance with antimalarial therapy is often suspected but difficult
      to prove, this study attempted to establish a model for predicting the plasma
      concentration of phenobarbital (given in low doses in conjunction with the drug)
      as an indicator of compliance. Phenobarbital was chosen because its value had
      been demonstrated as a marker of compliance in long-course therapies, any
      significant departure from steady-state concentrations (achieved with full
      compliance) indicating one or more missed doses. Therapy for uncomplicated
      malaria varies from 5 days with artesunate to 7 days with quinine + tetracycline.
      Volunteers with confirmed falciparum malaria were randomized into 5 groups and
      given malaria therapy as well as phenobarbital daily for 3-7 days. Plasma samples
      for determination of phenobarbital concentrations were taken just prior to the
      daily dose of phenobarbital. Although there was a clear and predictable
      individual pattern of blood concentrations following each dose of phenobarbital,
      inter-individual variation in blood levels was significant and reduced their
      predictive value beyond the second day's dose. The cause of the variations is not
      clear; it could be attributable to different sources of the drug, previous intake
      of phenobarbital by the patient, or differences in drug absorption and
      disposition in malaria patients. Results for the 5-day artesunate regimen suggest
      that phenobarbital may be useful as a marker of compliance if the patient stops
      medication after 3 days; clear differences were evident at the end of the course
      of treatment between plasma phenobarbital concentrations in individuals
      completing the 5-day course and those who stopped after 3 days. For the quinine
      tetracycline regimen, results suggest that it may be possible to discriminate
      between subjects where there is a 3-day difference in treatment. Phenobarbital is
      a better discriminant when dosing is every 24 hours as with artesunate, rather
      than the 8-hourly regimen for quinine-tetracycline. When measuring compliance for
      malaria treatment, if it is important to know what proportion of patients reach
      3, 5 or 7 days of compliance, then phenobarbital might have a role to play in
      this assessment, but further investigations in more patients would be required.
      Alternatively, different markers could be used for the doses to be given on these
      days and, as long as the patient does not mix the doses for the different days,
      sequential doses and determination of compliance could be based on an "all or
      none" detection of the marker rather than on drug levels.

PMID- 9763726
TI  - Diphtheria in visitors to Africa.

PMID- 9763727
TI  - Surveillance of overwhelming post-splenectomy infection.

PMID- 9763728
TI  - [Proceedings of the 26th Seminar on Environmental Hygiene. "Ecological Animal
      Raising" Hannover, 27 February 1998].

PMID- 9763729
TI  - [Consumer demands concerning meat between price and ethics].
AB  - A review is given about consumer demands on meat. Mainly the problems of
      decreasing meat consumption, health aspects and special questions of ecological
      products are considered. The market gives evidence of a further drop in meat
      consumption and a more consistent differentiation of product lines. Eco-products,
      emphasising the animal welfare aspect, will have their place in that context but
      persist in the state of a minor market segment. Nevertheless it has to be
      expected, that also the conventional products will increasingly comply to modern
      consumer demands.

PMID- 9763730
TI  - [Characteristic features of ecological animal husbandry].
AB  - In recent years conventional livestock farming has been impressively successful
      referring to the increase in performance of farm animals and to the decrease in
      production costs. On the contrary, following the dictate of production
      intensification, animal health and welfare as well as environmentally friendly
      production have been pushed into the background because of being cost- and labour
      intensive. Evaluations of animal health status of farm animals indicate that a
      considerable number of farm animals cannot cope with the requests of increase in
      performance. This may be due either to physiological limits or inadequate housing
      and management conditions. Ecological animal husbandry as an integrative Part of
      organic farming is an alternative to the previous development, aiming at high
      quality standards concerning animal health and welfare as well as environmentally
      friendly production. Farmers have to follow the code of practice before being
      entitled to label their products as organic food and demand for premium prices.
      The willingness of an increasing number of consumers to pay premium prices
      enables the farmers to balance the economical pressure on the production costs
      and on the yields of the farm animals. While the code of practice limits the
      amount of area-born products, options are gained for the optimization of the
      production process for the benefit of the farm animals and the environment. The
      capacities of ecological animal husbandry for high process quality standards are
      discussed hypothetically. Due to the phenomenon of various influences and
      interactions there is still a lack of methodology in order to assess the process
      qualities and the implications of different farming strategies in a complex and
      objective manner, resulting in a new challenge for natural science to establish a
      methodology that enables a more comprehensive approach.

PMID- 9763731
TI  - [Provision of a legal framework for ecological animal husbandry].
AB  - Since 1991 the Regulation (EEC) no. 2092/91 on organic production of agricultural
      products is applied for plants and plant products. Because of the increasing
      consumer's demand this regulation has to be supplemented by the area of livestock
      production. At present an amended commission proposal is discussed which also
      includes the amendments of the European Parliament. Besides the general
      principles of livestock production in organic farming the conversion periods from
      conventional to organic farming, the origin of the animals, feed and supplements,
      veterinary treatments as well as housing conditions for livestock are described.
      The negotiations in Brussels will have to achieve a compromise which gives a
      clear distinction from conventional livestock production, and which allows as
      many farms as possible, that are producing according to the rules of organic
      farming under various conditions within the EU member states, to proceed with
      minor adaptations to the new regulation.

PMID- 9763732
TI  - [Ecological animal husbandry--main developmental points for production and
      marketing as in the example of the Bioland Association].
AB  - The data from Bioland are presented as an example of the development in
      ecological animal husbandry. Dairy cows (29.000 in 1000 dairy farms) are typical
      in organic farming. In the past 4 years there has been an annual increase in
      dairy farming of about 6.5%. The increase is even higher in suckled cows and
      laying hens (both 23% annually), or apiculture. Pigs have been of minor
      importance, but are gaining more interest recently. In each category the number
      of animals is growing faster than the number of farms. In ecological husbandry,
      specialisation of personnel has to go hand in hand with improvements in keeping,
      feeding, hygiene, health of animals, integration of farming and stock breeding
      and documentation to cope with the demands of the market. The standard aimed for
      is dictated by the actual current state of knowledge in the ecological and
      ethological sciences. There are various possibilities for consultations and there
      are regional groups of specialists to provide know-how to the farmers.
      Ecologically produced goods are economically undersubsidised compared to
      conventionally produced ones. However, the development of the market is
      correlated with the production. The number of butcher's and dairies that have
      contracts with ecological associations has clearly been increasing lately. A high
      percentage of the raw products as well as food processed on the farm is sold
      directly by the farmers, however, there is a slow trend towards the retail trade.
      Various possibilities of improving the market are discussed. Ecological husbandry
      offers especially good conditions to farmers with high activity in marketing. The
      system of control is developing steadily according to the increasing demands in
      quality of production and products. As a result of good cooperation between
      farmers, control institutions and Bioland, practical solutions can be found to
      most problems. A list of high priority future work, investigation and development
      is given. All costs that arise during production and processing have to be
      internalised to widely realise ecological farming especially animal production in
      favour of environmental protection. Furthermore, farmers need an intensive
      education in agrarian ecology.

PMID- 9763733
TI  - [Special features of feeding in ecologic animal husbandry].
AB  - Food produced in ecological agriculture becomes popular more and more. In the
      interest of consumers (to protect against deception) and of producers (to
      contrast with conventionally produced food) it is necessary to define the
      conditions and circumstances when products can be declared as ecological. Up to
      now definitions of housing and feeding animals in organic agriculture only are
      set up by private organizations and associations, but in the future we will have
      a direction of the European community (Nr. 2092/91 EWG), extended by directives
      and restrictions focussed on animal husbandry and feeding. Aim of this
      contribution is to give information on special restrictions on feeds and feeding
      of food producing animals in organic agriculture (preconditions in the case that
      labelling as "ecologically produced" is intended). Conventionally produced
      feedstuffs are restricted, common complete diets and some special feed additives
      (for example growth promoters) are not allowed. Feeding according to species
      specific requirements (herbivorous animals) as well as according to age and
      development (for example minimum duration of suckling periods) is intended. On
      the other hand there is a conscious renunciation of maximizing animals'
      performance (and plant yields). Consequences, risks and conflicts of different
      aims in feeding in accordance with ideas of organic agriculture are discussed.
      Various efforts at sustainability of conventional agriculture are influenced
      markedly by ideas and concepts established in organic agriculture primarily.

PMID- 9763734
TI  - [Animal rights and animal health on ecological farms].
AB  - Intensive animal husbandry is criticized in relation to the fulfillment of the
      animals needs. The guidelines of the organizations of organic agriculture offer
      the opportunity for better animal welfare. In this paper an overview is given
      concerning animal health and welfare on organic farms with dairy cows, fattening
      pigs and laying hens. On organic farms housing systems with the potential for a
      better animal welfare dominate. In field studies using scoring systems (animal
      welfare index) organic farms reach more points than conventional ones. However,
      animal health on average is not much better on organic farms. The health problems
      discussed in the paper are mainly caused by management problems. Therefore,
      improvements are possible.

PMID- 9763736
TI  - [Economic management estimate of different environmentally-friendly animal
      husbandry systems].
AB  - This contribution compares conventional and ecological animal production systems.
      This financial analysis considers dairy farming and pig production and takes into
      account the individual options and aims of the farms. The profitability changing
      a conventional animal production system to an ecological system depends on many
      different parameters. A general statement with regard to all farms and farm
      systems is not possible. In addition to the farmers qualification, the marketing
      options, the location of the farm, the mode of operation and the financial
      situation when change to ecological production is envisaged determine prospects
      for success and profitability.

PMID- 9763737
TI  - [Quality of ecologically produced foods of animal origin].
AB  - The production of organic (ecological) food of animal origin is done in many ways
      and uses many different breeds. Therefore a real comparison with conventionally
      produced food is difficult. From the limited number of published data it appears,
      that the characteristics of quality of the products, the nutritional, hygienic,
      sensorial and technological factors, are not very different in both systems of
      production. In some factors organic food gets better marks, in others the
      conventionally produced food. The differences are in the production system
      (process quality) during lifetime of the animals.

PMID- 9763735
TI  - [Guidelines for prevention and therapy in ecological animal farms as in the
      example of bovine mastitis].
AB  - In ecological farming mastitis is the dominating disease in dairy cattle. The
      regular prophylactic use of antibiotics in farm animals is forbidden, in therapy
      antibiosis is restricted. A solution of this problem could be a program of
      systematic homeopathic prophylaxis as well as a standardised homeopathic
      treatment. The example of chronic catarrhal staph.-aureus-mastitis shows that
      there is only a certain expectancy of success by homeopathy as well as by any
      other medication, if the medication is combined with necessary sanitation
      measures. The prognosis for a homeopathic treatment is less favourable if the
      sanitation measures are realised incompletely. The possible negative effects of a
      false homeopathic medication are described.

PMID- 9763738
TI  - [Perspectives of ecological animal husbandry--limits of ecological animal
      husbandry].
AB  - Farms working under ecological conditions are as well as conventional farms a
      part of agriculture. Ecological farming is a response to the special requirements
      and ideas of consumers regarding environmental and nature related issues in
      primary agricultural production. Its products should be clearly defined so that
      they can be differentiated from conventional products. The limits of ecological
      livestock farming are set among others by comparably higher production costs,
      special management requirements, specific conditions from retailers in respect of
      quality and quantity and a limited demand. To further popularize ecological
      agriculture, the various individual interests must be focused and common
      strategies must be developed. To successfully claim market shares, the
      ecologically produced commodities must have a permanent advantage compared to
      conventional products-this will not be easy to achieve.

PMID- 9763739
TI  - [Post-antibiotic effect. A factor with clinical applications or simply a
      laboratory curiosity?].

PMID- 9763740
TI  - [Detection of pathogenicity factors in strains of classical enteropathogenic
      Escherichia coli].
AB  - OBJECTIVE: To determine the number of strains of classic enteropathogenic E. coli
      (EPEC) that have the eae gene, that is considered a pathogenicity factor.
      MATERIAL AND METHODS: The presence of the eae gene has been evaluated on 62 EPEC
      strains of ten different serogroups, isolated from children with gastroenteritis.
      RESULTS: Amplification of the eae gene was positive in 10 out of 62 EPEC strains
      analyzed (16%) corresponding to seven different serogroups. DISCUSSION: The low
      frequency of the detection of the eae gene on EPEC strains shows the limited
      correlation between the pathogenicity and the serogroup of the strains and would
      corroborate the need to reexamine this subject prospectively in our country.

PMID- 9763741
TI  - [Bactericidal activity and capacity for selection of mutants resistant to
      imipenmen and meropenem in strains of Proteus, Morganella and Providencia].
AB  - BACKGROUND: To compare the bactericidal activity and frequency of mutation for
      meropenem and imipenem against Proteus mirabilis, Morganella morganii and
      Providencia rettgeri. MATERIAL AND METHODS: Minimum inhibitory concentrations
      (MIC) were determined by agar dilution method. Bactericidal activities were
      evaluated by killing curves method employing 4 and 16x MIC. One-step resistant
      mutant selection was performed by spreading more than 5 x 10(8) UFC/ml on cystine
      lactose-electrolyte deficient agar containing 4 times the MIC of meropenem or
      imipenem. RESULTS: MIC were 8 to 16 times lower for meropenem. After 24 h,
      bactericidal activity was observed for meropenem at 4 and 16 x MIC against 76.7
      and 100% of the strains in comparison to 26.7 and 83.3% with imipenem. After 24 h
      incubation with imipenem, re-growth occurred in 80 and 90% of P. mirabilis and M.
      morganii strains, respectively. Imipenem resistant mutants were selected from 3
      strains of P. mirabilis. One of them was stable and MIC of meropenem and imipenem
      were 8 to 16-fold higher. CONCLUSIONS: From the laboratory point of view we
      consider that meropenem is more active against Proteeae because it was more
      potent in terms of inhibitory and bactericidal activity. In addition the risk to
      select for resistant mutants was significant with imipenem and P. mirabilis.

PMID- 9763743
TI  - [Comparison between 2 monoclonal antibodies (clones 95/12 and 1C3 + AYm-1) for
      the detection of pp65 antigenemia associated with human cytomegalovirus].
AB  - BACKGROUND: A prospective parallel and blind comparative study was carried out to
      evaluate the diagnostic efficacy of two available anti-pp65 monoclonal antibodies
      (clone 95/12 and the pool 1C3 + AYM-1) for the cytomegalovirus (CMV) antigenemia
      assay. MATERIAL AND METHODS: We carried out a comparative study of 107 blood
      samples from immunodepressed patients (renal transplant and AIDS patients) with
      suspected disseminated infection by CMV. The PMNLs were obtained using the method
      of sedimentation in saline dextran. Slides were stained by an indirect
      immunofluorescence assay with two commercially available monoclonal antibodies.
      RESULTS: Of the 107 blood samples studied 33 (30.8%) had a positive antigenemia
      test. The clone 95/12 detected 30 (90.9%) samples and the pool 31 (93.9%), no
      statistically significant difference was observed in the sensitivity of two
      reagents (p = 0.42). The values of the mean CMV-positive cell count obtained with
      the clone 95/12 was 60.6 vs 61.9 with the monoclonal pool (p = 0.026).
      CONCLUSIONS: No significant difference was detected between the two commercial
      monoclonal antibodies. However the pool detected a slightly superior CMV-positive
      cell count.

PMID- 9763742
TI  - [Association of Lyme disease with work and leisure activities].
AB  - BACKGROUND: The conditions for Lyme disease are ideal in northern Spain, but the
      risk factors are not well established. OBJECTIVE: To describe the clinico
      epidemiological characteristics of those patients hospitalized with the diagnosis
      of Lyme disease in a region of northern Spain (Vizcaya). PATIENTS AND METHODS:
      Retrospective analysis of the patients hospitalized with Lyme disease in Vizcaya
      between 1989 and 1996. RESULTS: Twenty-six cases met the clinical and serologic
      CDC criteria, 21 males and 5 females, with a mean age of 52 years. Neurologic
      manifestations were most common (73%), followed by erythema migrans (62%),
      arthralgias (38%) and arthritis (15%). Fifty-eight percent of the patients
      recalled a tick bite and rural professional or recreational activities were the
      main risk factors. Most of the patients did not seek medical help until late in
      the disease, which led to greater morbidity. CONCLUSIONS: Increasing number of
      Lyme disease cases in northern Spain represents a public health problem. Disease
      morbidity could be reduced by targeted education to populations at risk.

PMID- 9763746
TI  - [Population structure and bacterial clonality].

PMID- 9763744
TI  - [Antibiotic sensitivity of Streptococcus pyogenes in pediatrics].
AB  - BACKGROUND: The purpose of this study was to set up the current level of
      Streptococcus pyogenes sensitivity, in pediatric patients in our community, to
      penicillin, clindamycin, clarithromycin, erythromycin and azithromycin. MATERIAL
      AND METHODS: 100 strains were collected between October 1996 to July 1997. 79
      were pharyngeal and 21 were non-pharyngeal strains. The MICs were obtained by the
      E-test method, and furthermore the results were compared by the Kirby-Bauer
      method. RESULTS: All strains were sensitive to penicillin and except one
      (inducible resistance) to clindamycin. 19% were resistant to macrolide, without
      differences among clarithromycin, erythromycin and azithromycin. From 13 strains
      (16.5%) of pharyngeal and 6 (28.5%) from non-pharyngeal samples, 4 of these from
      cutaneous samples, showed resistance. 18 of the resistance strains belonged to
      novel resistance fenotip and one to 10 inducible fenotip. Only minor
      discrepancies about erythromycin and clindamycin were observed between E-test and
      Kirby-Bauer methods. CONCLUSIONS: This study confirms a remarkable level of
      resistance to macrolides in pediatric patients, mainly in the cutaneous samples.
      Due to the reduced prevalence of macrolide-susceptible strains, in vitro
      susceptibility testing appears necessary in case of macrolide chemotherapy.

PMID- 9763748
TI  - [Pulmonary mass which cavitated after bronchoscopy].

PMID- 9763747
TI  - [Intranasal necrotic lesion in a neutropenic patient].

PMID- 9763749
TI  - [Psoas abscess caused Actinomyces israelii].

PMID- 9763750
TI  - [Endocarditis caused by Moraxella lacunata on the natural and prosthetic valves.
      An unusual pathogenesis].

PMID- 9763751
TI  - [Cat scratch disease: description of a new case].

PMID- 9763752
TI  - [Bacteremia caused by Moraxella catarrhalis].

PMID- 9763753
TI  - [Multiple cerebral abscesses with spontaneous emptying into the ventricles and a
      good response to meropenem].

PMID- 9763754
TI  - [Cerebral abscess caused by Rhodococcus equi in an immunocompetent patient].

PMID- 9763755
TI  - [Bacterial meningitis caused by a meningoencephalocele 20 years after a head
      injury].

PMID- 9763756
TI  - The relevance of recent advances in psychopharmacology for social psychiatry.

PMID- 9763757
TI  - [The importance of recent neuropsychological and neurophysiological studies for
      social psychiatry].

PMID- 9763758
TI  - Relevance of brain imaging studies for social psychiatry.

PMID- 9763759
TI  - [Genetic studies and their relevance in social psychiatry].

PMID- 9763760
TI  - [Patterns of care in community mental health services in Lombardy].
AB  - OBJECTIVE: The analysis aims to study patterns of care of patients in contact
      with 5 Psychiatric Services in Lombardy. Four patterns have been identified long
      term-high users, non long term-high users, long term-non high users, non long
      term-non high users. DESIGN: Data were provided by the regional Psychiatric
      Information System. The cohort of patients have been composed by 5,670 patients
      included in 1994 one year prevalence. SETTING: Five Psychiatric Services (Merate,
      Treviglio, Crema, Desio, Castano Primo) with a total population of 610,184
      inhabitants aged over 14. MAIN UTILISED MEASURES: Some sociodemographic and
      clinical variables have been taken into consideration for a descriptive analysis;
      a multinomial logistic regression model was used to identify the characteristics
      of patients associated with different patterns. RESULTS: Long term-high users
      were 5.3%, i.e. a mean rate of 4.9/10,000 residents over 14, and absorbed 60% of
      resources, the absence of a partner was associated in regression analysis with
      this pattern. Non long term-high users were 1.2%, i.e. a mean rate of 1.1/10,000
      residents over 14, and absorbed 7.8% of resources; age below 45, unemployment,
      absence of a partner, severe mental illness and first contact with Psychiatric
      Services in the period 1985-1989 were predictive variables. Long term-non high
      users were 23.4%, i.e. a mean rate of 21.6/10,000 residents over 14, and absorbed
      18.1% of resources; age below 45, unemployment, living alone, absence of a
      partner, severe mental illness and first contact with Psychiatric Services before
      1990 were predictive variables. Non long term-non high users were 70.1%, i.e. a
      mean rate of 64.8/10,000 residents over 14 and, absorbed 18.1% of resources.
      CONCLUSIONS: Data show that on the whole the activity of Psychiatric Services is
      addressed to most serious patients, though considerable differences between
      Psychiatric Services utilisation may be found. This study highlights the
      importance of a regional Psychiatric Information System, that allows the
      monitoring in time and in the regional territory of patterns of care.

PMID- 9763761
TI  - [Quality evaluation in psychiatric services: a regional system of indicators].
AB  - OBJECTIVE: This work proposes a series of indicators, based on routine data
      collection system adopted in the Emilia Romagna Region, with the aim of
      describing the quality and quantity of psychiatric care and the connections of
      psychiatric structures. We are bearing in mind the Plan aimed to Mental Health
      Care 1994-1996 and the Efficiency and quality indicators of National Health
      System (SSN) devised by the Department of Health of national government. METHOD:
      A working group has been instituted by the regional authority to define the
      indicators (definition of meaning, formula, danger level, finality, level od
      utilisation, data source and frequency of survey, congruent with the regional
      information system. RESULTS: We present 105 indicators grouped according to the
      psychiatric structure they are aimed at (community centers, acute admissions
      wards, semiresidential and residential facilities, former mental hospitals,
      district mental health department) and according to code in three lists: 1)
      general indicators; 2) probing indicators; 3) outcome indicators. CONCLUSIONS:
      This set of indicators though created for local usage is aimed on objectives
      defined by the national Department of Health and can therefore be of interest for
      other Italian regions. Modular construction permits flexible application ad
      adaptation to less complex information systems. Part of this system is since 1977
      part of routine information flux in Emilia Romagna.

PMID- 9763762
TI  - Linking epidemiology and disability measurement with mental health service policy
      and planning.
AB  - OBJECTIVE: This article reviews the extent to which epidemiology and disability
      measurement can contribute to mental health and service policy and planning.
      METHODS: The review explores the information required for local, mental and
      international policy and planning in a variety of settings. RESULTS: Epidemiology
      and disability measurement are essential to underpin policy and planning that are
      responsive to local needs, together with information on service inputs and
      processes and health outcomes. CONCLUSIONS: Epidemiology and disability
      measurement should be an integral part of the policy and planning process to
      support the development of service, and service processes and the measurement of
      health outcomes for not only specialist mental health services, but also
      activities in primary care, schools and workplaces.

PMID- 9763763
TI  - System failure? The problems of reductions in long-stay beds in the UK.
AB  - OBJECTIVE: To review the relevant literature on the effects of reductions in long
      stay beds on mental health services in the UK. METHOD: A selective literature
      review, with particular reference to research conducted by the author and
      colleagues at The Sainsbury Centre for Mental Health. RESULTS: The evidence
      suggests that the effects of long stay bed reductions should be examined with
      regard to 'old' and new long stay patients separately. While the 'old' long stay
      who have been most directly effected by these changes have generally fared well;
      the 'new' long stay have not. They are currently accumulating in acute inpatient
      units, often on general hospital sites, or are rotating in the 'revolving door'
      of acute inpatient care and inadequate community supports. Although it is clear
      that there is a shortage of acute beds especially in inner city areas many of the
      these beds are currently occupied by patients who would be better (and less
      expensively) cared for in community alternatives if these were available. The
      evidence suggests that it is possible to improve outcomes for this 'new' long
      stay group if specific kinds of housing, work and assertive community teams are
      provided. CONCLUSIONS: It is concluded that the effects of long stay bed
      reductions should be considered in a 'systems perspective. Effective community
      services can be established, but in order to achieve effective substitution of
      one kind of service for another, there must be a well co-ordinated, clearly
      targeted, and technically efficient system. At the present time such services are
      rare. However, simply focusing on one element (e.g. beds) is unlikely to produce
      cost effective and efficient solutions.

PMID- 9763765
TI  - First reported case of hantavirus pulmonary syndrome in Oklahoma.
AB  - Hantavirus Pulmonary Syndrome (HPS) is a condition of rapidly progressive
      pulmonary failure with a case-fatality rate of almost 50 percent. Rodents serve
      as the reservoir for hantaviruses and human infection occurs primarily via
      aerosolized virus in rodent excreta. The rodent reservoir for the disease is
      widespread across Oklahoma and the first case of HPS has recently been confirmed
      in an Oklahoma resident. Physicians should suspect HPS in a previously healthy
      person who develops a febrile illness and respiratory insufficiency and has
      potentially been exposed to the virus. Common laboratory findings include a left
      shifted neutrophilic leukocytosis, elevated hematocrit and thrombocytopenia.
      Therapy is supportive. If HPS is suspected, the patient should be immediately
      transferred to a facility that can provide aggressive supportive care.

PMID- 9763764
TI  - [Medical decisions at the end of life: epidemiological and psychiatric aspects].
AB  - OBJECTIVE: Despite the ongoing moral and legal debate, there is still a paucity
      of empirical literature on the actual occurrence of Medical Decisions at the End
      of Life (MDEL). Moreover, the psychiatrist's role in this scenario is still
      unclear. METHODS: This paper systematically reviews currently available
      literature on euthanasia (EU) and physician assisted suicide (PAS). Published
      articles were selected if they reported either: 1) prevalence estimates of
      patients' requests of EU/PAS; and/or 2) prevalence estimates of physicians'
      actual EU/PAS practices. Papers exploring the issue of MDEL-related psychiatric
      consultation have been also included in the review. RESULTS: The empirical
      evidence reported in this paper shows that EU/PAS demands and acts are not
      uncommon in medical practice. A conservative estimate indicates that at least 10%
      of physicians have granted a request of EU/PAS. The involvement of consultation
      liaison psychiatrists in MDELs seems to be relatively rare. CONCLUSIONS:
      Euthanasia and other MDELs require physicians' thoughtful evaluation of criteria
      guiding professional decision-making. To this purpose, epidemiological and
      psychosocial research can offer a valuable contribution.

PMID- 9763766
TI  - Patient-physician E-mail communication.
AB  - A significant number of Oklahomans are using computers and have e-mail access
      either at home or at work. Consecutive patients seen by 23 family physician
      members of the Oklahoma Physicians Research/Resource Network (OKPRN) were queried
      regarding their use of computers and access to e-mail. The numbers are higher in
      urban and suburban areas than in medium and smaller towns and rural areas. Of
      those who have e-mail access now or are planning to get it within six months, a
      substantial majority would like to use this medium to interact with their family
      physician. Potential uses for e-mail technology and problems to be overcome are
      discussed.

PMID- 9763767
TI  - A breach of trust: passing the wealth.

PMID- 9763768
TI  - Marrow and stem cell transplantation in Oklahoma: fifteen years of experience and
      results.
AB  - From September 1982 to August 1997, 767 bone marrow or peripheral blood stem cell
      transplants have been performed at the Health Sciences Center in Oklahoma. Five
      hundred and two (502) autologous transplants (AutoTX) preceded by high-dose
      myeloablative therapy were performed for breast cancer (BC, 36%), non-Hodgkin's
      lymphomas (NHL, 24%), Hodgkin's disease (HD, 10%), acute myeloid leukemia (AML,
      8%), testicular cancer (TC, 4%), multiple myeloma (MM, 2%) and other malignancies
      (16%). Two hundred and sixty-five (265) allogeneic marrow transplants (AlloTX)
      (related, unrelated) were carried out in chronic myeloid leukemia (CML, 30%), AML
      (23%), acute lymphoid leukemia (ALL, 14%), myelodysplastic syndrome (MDS, 9%),
      severe aplastic anemia (SAA, 8%), and other diseases (14%). Compared between
      1980s to 1990s, 100-day mortality rates have decreased from 28% to 5% for AutoTX
      and from 40% to 25% for AlloTX. In the AutoTX setting, major changes included the
      routine use of growth factors post-transplant and the switch from bone marrow to
      growth factor-mobilized peripheral blood as a source of stem cells over the last
      five years. In the AlloTX setting, improvements in recognition and control of
      cytomegalovirus and Candida organisms, the selective use of growth factors and
      screened blood products, and better selection of unrelated donors using DNA-based
      techniques of HLA-matching have contributed to reduce early mortality from
      infection and primary graft failure. The five-year survival outcomes are
      comparable to those reported in registry data from the International Bone Marrow
      Transplant Registry (IBMTR) and the National Marrow Donor Program (NMDP).

PMID- 9763769
TI  - De-mystifying social security disability adjudication: the physician's role.

PMID- 9763770
TI  - The sick building syndrome: a danger to your health.

PMID- 9763771
TI  - The state of the state's health. A report from the Oklahoma State Board of
      Health.

PMID- 9763772
TI  - The influence of affect on social-information processing.
AB  - This study examined the impact of four affect induction conditions (self-induced
      positive affect, music-induced positive affect, music-induced negative affect,
      and neutral affect) on the social-information-processing skills of 96 seventh
      grade students with and without learning disabilities using the Dodge (1983)
      model of social skills. Following a 1-minute affect induction, students were
      presented with a social problem and asked a series of questions that tested their
      social skills. Although the results did not find significant differences between
      school-identified students with and without learning disabilities, there were
      significant main effects for language skills and affect induction. Students above
      the median on the Iowa Test of Basic Skills language test generated more
      solutions and fewer negative responses than students below the median. Students
      in the self-induced positive affect condition generated more solutions, whereas
      students in the music-induced positive affect condition generated more
      embellishments and perceived less interpretation (negative/positive), than
      students in the neutral and negative affect conditions. The implications of these
      results for research and practice are discussed.

PMID- 9763773
TI  - Social outcomes for students with and without learning disabilities in inclusive
      classrooms.
AB  - Social outcomes of students who participated in two different educational
      settings designed to provide special services for students with learning
      disabilities (LD) placed full-time within the general education classroom were
      examined. Participants were 185 third-through sixth-grade students: 59 students
      with LD, 72 low to average achieving, and 54 high achieving. There was an overall
      educational setting effect, with students on the consultation/collaborative
      teaching setting demonstrating more positive outcomes than students in the co
      teaching setting on friendship quality and peer acceptance. Students with LD in
      the consultation/collaborative teaching setting also demonstrated moderate
      increases in the number of reciprocal friendships from fall to spring. Discussion
      addresses the positive social outcomes for students with LD and high-achieving
      students in the consultation/collaborative teaching setting, and the importance
      of monitoring student progress in all settings.

PMID- 9763774
TI  - Perceptions of academic strategies and competence in students with learning
      disabilities.
AB  - Research findings regarding general self-concept, academic self-concept, and self
      awareness in students with learning disabilities have varied, and results are
      still inconclusive regarding the consistency between students' and teachers'
      judgments of academic performance. The current study focuses on students' and
      teachers perceptions of the students' strategy use and performance in nine
      different academic and organizational domains. Six hundred sixty-three students
      and their 57 teachers were involved in the study. Findings indicated that the
      students with learning disabilities considered themselves appropriately strategic
      and competent in the five domains of reading, writing, spelling, math, and
      organization. These students also rated their academic performance and
      organization as average to above-average in seven of nine domains, with the
      exception of checking and planning their work. Nevertheless, the self-ratings of
      the students with learning disabilities were still significantly lower than the
      self-ratings of average achievers in virtually all domains. The second major set
      of findings revealed a sharp discrepancy between the self-assessments of the
      students with learning disabilities and their teachers' judgments. Teachers rated
      the students with learning disabilities as weak in their strategy use and below
      average in their performance in all nine academic and organizational domains.
      Finally, gender differences were not evident in eight of the nine domains. These
      results have added to the increasing body of literature indicating that students
      with learning disabilities frequently perceive themselves as capable and
      effective and often rate themselves as academically stronger than their teachers
      judge them to be.

PMID- 9763775
TI  - Investigating reading disabilities using the rauding diagnostic system.
AB  - Should a measure of intelligence be replaced by a measure of listening in
      discrepancy definitions of reading disability? This question was answered using a
      newly developed diagnostic system, which is based on "rauding" theory and a
      causal model of reading achievement. In Study 1, diagnostic results were analyzed
      from 122 students in Grades 3 through 7 who took, via computer, a battery of
      tests called the computer Assisted Reading Diagnosis (CARD). In Study 2, 44
      university students were given the CARD. In Study 3, the CARD was administered to
      128 students in reading improvement classes at a suburban community college. From
      the results, it was concluded that the rauding diagnostic system consistently
      diagnoses disabilities in listening, decoding, and naming speed when they are
      theoretically needed to explain accuracy and rate disabilities of children and
      adults who are poor readers. It was recommended that (a) general intelligence,
      fluid intelligence, or IQ not be used to measure potential or to diagnose reading
      disabilities; (b) listening not be used to measure potential; (c) verbal
      knowledge aptitude, pronunciation aptitude, and cognitive speed aptitude be used
      to measure potential; and (d) the new rauding diagnostic system replace the
      system of diagnosing dyslexics, hyperlexics, and garden-variety poor readers.

PMID- 9763776
TI  - A validation of the role of preschool phonological and orthographic skills in the
      prediction of reading.
AB  - Two cohorts of children were followed to determine whether tests of phonological
      awareness (Syllable Tapping), orthographic processing (Visual Matching), and
      serial naming speed (RAN Objects), added to a preschool battery, would improve
      prediction of reading. The major predictors of first-grade reading and spelling
      were preschool letter naming and sentence memory for both cohorts, but the
      orthographic and serial naming tasks added a small amount of additional variance.
      Sentence memory accounted for the most variance in second-grade reading for both
      cohorts, and Visual Matching made contributions to reading and spelling for each
      cohort. Sentence memory, Visual Matching, and color naming together yielded an
      87% to 90% hit rate in predicting which individual children would be good or poor
      readers. The orthographic and serial naming speed tasks are useful additions to a
      preschool predictive battery, but recommendations are that alternative preschool
      phonological tasks, not based on syllable recognition, should be used to predict
      reading.

PMID- 9763777
TI  - The performance of students with disabilities in a norm-referenced, statewide
      standardized testing program.
AB  - Hawaii uses the Stanford Achievement Test, 8th Edition (Stanford 8), to assess
      the academic performance of students in Grades 3, 6, 8, and 10. Three
      longitudinal cohorts were analyzed for achievement performance among Grades 3 to
      6, 6 to 8, and 8 to 10. ANOVAs indicated significant differences in overall
      performance between nondisabled students and three high-incidence categories of
      students with disabilities (specific learning disability, emotional impairment,
      and mild mental retardation). Local subgroup norms were developed on the basis of
      Stanford 8 reading and mathematics results from 1992 to 1996 to supplement the
      national norms and provide an additional means of comparison to evaluate
      performance for these categories. The longitudinal cohorts of students with
      disabilities made greater gains in achievement from third to sixth grade than
      their national counterparts and cohort of nondisabled students in Hawaii. Between
      8th and 10th grade, students with learning disabilities and emotional impairments
      made gains equal to or greater than their national counterparts'.

PMID- 9763779
TI  - False starts and other dilemmas of a secondary general education collaborative
      teacher: a case study.
AB  - Currently, many special education policymakers, researchers, and practitioners
      are questioning the efficacy of pull-out programs for students with disabilities
      and advocating service delivery in inclusive or general education settings at
      both the elementary and the secondary level. I investigated the implementation of
      a collaborative teaching model in a suburban high school to determine how this
      move toward inclusive education benefited teachers and students. Through
      examination of the "ups and downs" of a U.S. History teacher, I concluded that
      replicating and sustaining collaborative teaching can be difficult and complex
      and, without careful consideration of contextual variables, may not lead to
      improved outcomes for either teachers or students. Implications for research and
      practice are discussed.

PMID- 9763778
TI  - Cognition in children does not suffer from very low lead exposure.
AB  - We studied the relationship between exposure to lead and memory and attention in
      children. Participants were 313 boys aged 9 to 12 years who attended special
      education schools in the Netherlands. Children whose possible attentional or
      memory problems were obviously due to causes other than lead contamination were
      excluded from the study. Cognition was assessed by extensive theory- based
      testing. Blood lead concentration was measured to assess body lead burden.
      Possible confounding factors that might affect blood lead level and/or cognitive
      functioning were assessed. Blood lead levels were higher in children with lower
      socioeconomic status and in children with more hand-to-mouth behavior, and varied
      seasonally, with higher values in spring and summer. The mean blood lead level
      was 44.4 microgram lead per liter blood, which is considered low. Only 2% of the
      children showed a slightly higher blood lead level than the American safety
      standard. To obtain robust measures of cognitive aspects, we performed a factor
      analysis. The results showed that blood lead level did not influence any of the
      cognitive factors. Therefore this study, despite being designed to maximize the
      chance of finding an effect in asymptomatic children, does not support a
      relationship between lead at very low doses (below 100 micrograms/liter blood)
      and cognition in schoolchildren.

PMID- 9763780
TI  - Why does my stomach hurt? How individuals with learning disabilities can use
      cognitive strategies to reduce anxiety and stress at the college level.

PMID- 9763781
TI  - Hearing voices, witnessing pain: in response to "why does my stomach hurt?".

PMID- 9763782
TI  - [Function cerebral MRI].

PMID- 9763783
TI  - [What is your diagnosis? A mass in the lateral ventricle].

PMID- 9763784
TI  - [Intracranial dural arteriovenous fistula with perimedullary venous drainage].
AB  - Two cases of intracranial dural arterio-venous fistula (DAVF) with perimedullary
      venous drainage are reported. In both cases, MRI T2-weighted (T2W) images showed
      an hypersignal within the cervical cord with sparing of the thoracic cord. In one
      case perimedullary vessels were demonstrated on T1W images after gadolinium i.v.
      administration. A complete spinal angiogram did not show evidence of fistula but
      demonstrated the lack of opacification of the conus medullaris venous drainage.
      Cerebral angiogram demonstrated in the first case a foramen magnum DAVF and in
      the second case a petrous apex DAVF. Hypersignal limited to the cervical cord at
      MRI on T2W images remain exceptionnal in case of intracranial DAVF with
      perimedullary venous drainage. When neurological symptoms are suggestive, post
      gadolinium T1W sequences should be conducted, followed by selective spinal
      angiogram. If normal venous drainage is not objectivated (e.g. opacification of
      radiculo-medullary veins on the late phase), cerebral angiogram should be done to
      rule out an intracranial DAVF.

PMID- 9763786
TI  - [Deep cerebral venous thrombosis].
AB  - Deep cerebral venous system thrombosis is uncommon and is usually encountered in
      children, generally in the neonatal period. In adults, this pathology is even
      more exceptional. We report two cases in adults. Deep cerebral venous system
      thrombosis mainly affects women taking oral contraception. The most common
      clinical pattern combines headaches and confusion. A comatose state is rather
      exceptional. This pathology, formerly considered to have poor prognosis, has
      benefited from diagnostic and therapeutic progress. Favorable outcome has been
      achieved in several recent cases, as one of ours, without after-effects.
      Diagnosis, often suggested by the CT-scan, is based on MRI associated with MRA.
      Thrombus formation is easily diagnosed by MRI at the subacute stage, but far less
      easily at the acute and chronic stages as the low signal is identical to the
      normal flow void. MRA, in phase contrast or time of flight sequences, is highly
      interesting at the acute phase. In case of doubt, an angiography can be applied.
      Therapy is based on heparin. The contribution of local infusion of thrombolytic
      agents, recently used with success, remains to be determined.

PMID- 9763785
TI  - Vasodilating in MR-angiography: a comparison of techniques.
AB  - PURPOSE: To verify the hypothesis that a drug that causes vasodilation can
      contribute to improvement in MRA spatial resolution. To test this hypothesis, a
      comparison was made between the images obtained using the high resolution time-of
      flight (TOF HR 3D) technique and the TOF 3D MTC TONE technique. METHODS: From
      November 1993 to December 1994, we studied 40 patients, of which 20 patients (16
      males and 4 females; average age of 10 years; range from 3 to 20 years) we
      examined after they had inhaled Isoflurane (experimental group), and 20 patients
      (16 males and 4 females; average age 9.7 years; range from 3 to 12 years) were
      examined with standard MRA (control group). RESULTS: The vasodilator in both HR
      MRA and MTC TONE MRA permits a better spatial visualization with respect to the
      clinical routine MRA. On the other hand, it is true that MTC TONE gives better
      visualization of the small vessels. DISCUSSION: In our experience, this
      preliminary study indicates that with respect to routine MR, the spatial
      resolution is notably increased when Isoflurane is used. The signal-to-noise
      ratio is increased but, moreover, the ability to visualize small vessels is
      increased. CONCLUSION: The preliminary results obtained in this study indicate
      that a pharmacological drugs is capable of increasing the vascular detail of MRA
      images of the intracranial vessels and that continued research this direction is
      called for.

PMID- 9763787
TI  - [Percutaneous vertebroplasty of the cervico-thoracic junction using an anterior
      route. Technique and results. Report of nine cases].
AB  - Percutaneous vertebroplasty using fluoroscopy is a well known technique.
      Visualization of the posterior wall of the vertebra is mandatory. Good assessment
      of this part of the vertebra is usually difficult at the cervico-thoracic
      junction. We propose an original method to obtain adequate visualization of the
      posterior wall, avoiding the shoulders superposition. Using this technique, we
      performed twelve vertebroplasties in nine patients (one angioma and eleven
      metastatic lesions). Clinical outcome was good for all patients, even a total
      filling of the vertebra body by the cement was obtained in only eight cases on
      twelve. No clinical complication was observed.

PMID- 9763789
TI  - Cervical osseous changes associated with vertebral artery tortuosity.
AB  - Vertebral artery tortuosity causing neural foraminal widening is a well described
      abnormality that should not be confused with other causes of neural foraminal
      enlargement, particularly on conventional roentgenograms. We, hereby, describe CT
      features of another cervical osseous change due to the vertebral artery
      tortuosity, the so called "tubular shaped vertebral artery canal", which is
      embedded in the vertebral body instead of causing neural foramen enlargement.
      Catheter and MR angiographic studies have also been performed to confirm the
      vertebral artery tortuosity causing the osseous changes.

PMID- 9763788
TI  - [Comparison of three fat suppression sequences for the detection of vertebral
      detection. Turbo STIR, phase contrast gradient-echo, and MISTEC-Chopper after
      gadolinium injection].
AB  - OBJECTIVES: Assess three fat suppression sequences used to search for spinal
      metastases: TurboSTIR, phase contrast gradient-echo, and MISTEC-Chopper after
      gadolinium injection. MATERIAL AND METHODS: A prospective study was conducted in
      10 patients with primary neoplasia. MIR sequences acquired (1 Tesla) were
      TurboSTIR, T1 spin-echo with and without gadolinium injection, phase contrast
      gradient-echo and M-Chop after gadolinium injection. Signal intensity in normal
      bone marrow, metastatic tissue, and subcutaneous fat as well as background noise
      was measured. Signal-to-noise (S/N) ratio was determined. Lesion borders,
      artefacts, and extent of detected lesions were determined quantitatively. Bone
      marrow signal intensity was also recorded. RESULTS: S/N ratio was best with
      gradient-echo which identified well the borders of lesions within the hemopoietic
      marrow. For lesions located in high-fat marrow (as in post-radiation marrow), the
      high intensity signal of the lesion confounded with the fat signal. TurboSTIR
      gave effective fat signal suppression and was particularly useful for yellow
      marrow, less so for red marrow. This technique confounded cell proliferation with
      perilesional edema (enlarging lesion extention). In one case, this sequence did
      not detect a small lesion visible with the two other sequences. This sequence was
      sensitive to artefacts (especially vascular artefacts) which can produce false
      nodular images. M-Chop gave good suppression of vertebral fat tissue (better for
      yellow marrow) but subjective detection of lesions was more difficult.
      CONCLUSION: The phase contrast gradient-echo sequence after gadlinium injection
      appeared to be the best sequence excepting cases of post-trauma (radiotherapy or
      chemotherapy) fat transformation of the marrow where the TurboSTIR sequence could
      be preferred.

PMID- 9763790
TI  - [Hematomyelia complicating a spinal dural arteriovenous fistula. Report of a
      case].
AB  - We report a case of hematomyelia which led to sudden onset complete paraplegia in
      a 74-year-old man. Hematomyelia revealed a spinal dural arteriovenous fistula at
      level T8-T9. Spinal hemorrhage was observed in contact with a round-shaped
      aneurysmal like ectasia which undoubtedly ruptured. Treatment was embolization.
      Spinal atrophy followed and MRI one year after embolisation visualized the
      involution of the pathological vessels. We discuss the pathophysiology of this
      hemorrhagic accident and specific anomalies of the drainage veins in these
      malformations.

PMID- 9763791
TI  - Deep calcarine sulcus and prominent calcar avis.
AB  - MR imaging examinations of the brain 100 consecutive patients, ages ranging from
      1 year to 66 years, were evaluated in order to investigate the frequency of a
      deep calcarine sulcus and prominent calcar avis. Twenty-four cases (24%) were
      found with a deep calcarine sulcus and prominent calcar avis. These were
      bilateral in four patients, and unilateral in twenty. Fifteen of the unilateral
      cases demonstrated a right-sided involvement, and remaining five were left-sided.
      A deep calcarine sulcus and prominent calcar avis should be distinguished from
      disorders of neuronal migration and organization such as schizencephaly and
      heterotopia. Also, based on our findings in this study, we speculate that it is
      the deep calcarine sulcus and prominent calcar avis which creates the appearance
      of the so-called accessory occipital ventricle.

PMID- 9763792
TI  - [Current imaging of an "aberrant course" of the internal carotid artery].
AB  - Blood flow via an aberrant internal carotid artery within the tympanic cavity is
      a rare pathogenic embryonic variation causing pulsatile tintinus and a
      vascularized tympanum. CT-scan provides the diagnosis. MRI and 3D time-of-flight
      MRA appear ideal for exploring aberrant flow both for diagnostic purposes and to
      establish the vascular morphology.

PMID- 9763793
TI  - Schizencephaly and congenital cytomegalovirus infection.
AB  - Congenital cytomegalovirus (CMV) infection is known to be associated with some of
      the disorders of neuronal migration and organization, including gray matter
      heterotopias, and polymicrogyria. We report a patient with schizencephaly and
      congenital CMV infection.

PMID- 9763794
TI  - Exercise, immune function and HIV infection.
AB  - The implications of HIV infection for exercise and sport are reviewed. HIV
      infection leads to impairment in a number of key elements of immune function,
      most obviously a progressive decline in the numbers of CD4+ T helper/inducer
      lymphocytes. Nevertheless, patients with early through moderately advanced HIV-1
      infection can engage in moderate sport and exercise without risk to themselves or
      other participants; the resulting gains of aerobic power and muscle strength are
      similar to those observed in healthy individuals of comparable initial fitness.
      In fully developed AIDS, the ability to exercise may be compromised by
      deteriorations in cardiorespiratory and neuromuscular function. Given the
      impairment of resting immune function, the potential immunosuppression from very
      intensive bouts of competitive exercise must be avoided. Review of all published
      papers to date provides a relatively limited data base. During a bout of moderate
      physical activity, HIV seropositive individuals apparently have an impaired
      ability to mobilize neutrophils, NK and LAK cells into the circulation.
      Nevertheless, programmes of moderate training can be sustained without any large
      change in CD4+ count or CD4+/CD8+ ratio. In some studies, training has also
      attenuated psychological stress, possibly for this reason checking the
      anticipated fall in CD4+ count. However, further large-scale randomized and long
      term studies of HIV are needed, comparing the therapeutic value of exercise alone
      with that of psychotherapy or a combined programme of exercise and psychotherapy.

PMID- 9763795
TI  - Effects of intensive endurance exercise on DNA damage in leucocytes.
AB  - OBJECTIVE: It has been shown that highly intensive anaerobic exercise induces DNA
      damage in leucocytes (LEU). The present study was designed to investigate whether
      intensive endurance exercise is capable of inducing comparable effects.
      EXPERIMENTAL DESIGN: A prospective study. PARTICIPANTS: Twelve men (aged 27.3 +/-
      4.1 years) who undertook a regular training of different extent (running volume
      45 +/- 25 km.week-1) volunteered in the study. INTERVENTIONS: The subjects
      competed in a half marathon (HM) of 21.1 km, 93.0 +/- 10.4 min. MEASUREMENTS:
      Blood was taken at rest, 1 and 24 hrs after HM for determination of creatine
      kinase, neutrophil (PMN), lymphocyte and monocyte counts. DNA damage in LEU at
      rest and 24 hrs after HM was quantified using the single cell gel-electrophoresis
      (SCG) assay. RESULTS: PMN increased from 2.81 +/- 0.69 to 13.13 +/- 2.91 1 hrs
      after HM (p < 0.01) and returned to 3.26 +/- 0.47 10(9) cells.l-1 by 24 hr
      recovery. DNA migration (image length, IL) reflecting the extent of DNA damage
      was elevated significantly in 10 of 12 subjects one day after HM. IL rose from
      32.7 +/- 2.2 to 40.7 +/- 3.9 microns (p < 0.01). Correlation analysis revealed a
      relationship between DNA migration 24 hrs after HM and PMN count 1 hr post
      exercise (r = 0.67, p < 0.05). CONCLUSIONS: The results confirm the hypothesis
      that DNA damage in LEU occurs after intensive endurance exercise. We suppose our
      observation of exercise-induced DNA damage in LEU is affected by reactive oxygen
      species which are released from PMN. It is quite unclear whether DNA damage in
      LEU is causal involved in exercise-induced modifications of the immune system.

PMID- 9763796
TI  - Effect of lactate consumption on exercise performance.
AB  - BACKGROUND: Maintenance of plasma glucose is important in endurance performance.
      Gluconeogenesis or carbohydrate ingestion maintain glucose after hepatic glycogen
      depletion. Lactate may also serve as a gluconeogenic precursor as well as a blood
      buffer. METHODS: To determine if an 8% carbohydrate (CHO) sports drink with and
      without a 2% lactate (L) solution increased endurance performance, peak power,
      and delayed blood acidosis, seven trained cyclists participated in a double-blind
      randomized study (6 males and 1 female) performed a bicycle test to determine max
      VO2max HR and the HR associated with the first respiratory exchange ratio (RER)
      value greater than 1.0 (target HR). Four bicycle rides to exhaustion, separated
      by one week, were done at a constant workload at a HR 10 beats below each
      subject's target HR. After a 12-hour fast, subjects received 100 g CHO 2-3 hrs
      before each test. Mean exercise heart rate was 86-87% max HR. During the final 30
      s of each ride the Wingate power test was performed. Subjects consumed either
      (placebo, 2% L, 8% CHO or 8% CHO plus 2% L) every 20 min. Blood samples were
      collected before, every 30 min during and immediately following the test.
      RESULTS: No significant differences were observed in total time (placebo: 95.3 +/
      25.8, 2% lactate: 95.7 +/- 30.0, 8% CHO: 105.2 +/- 37.2, 8% CHO + 2% lactate:
      89.0 +/- 28.1 min) or peak power (placebo: 798.2 +/- 241.1, 2% L: 750.1 +/-
      279.2, 8% CHO: 789.4 +/- 353.5, 8% CHO + 2% L: 716.3 +/- 331.3 Watts) among
      drinks. There were no differences in insulin, glucose, pH and HCO3- after the
      power tests among the drinks. CONCLUSION: Exercise performance is unaffected by
      oral supplementation with lactate.

PMID- 9763797
TI  - The effect of exercise intensity on the slow component of VO2 in persons of
      different fitness levels.
AB  - OBJECTIVES: To evaluate the slow component of VO2 in persons of different fitness
      levels exercising at different intensities and the contribution of proposed
      mediators to the slow component of VO2 using equations from the literature.
      EXPERIMENTAL DESIGN: Cross-sectional. SETTING: University. PARTICIPANTS: Low (N =
      15) and high (N = 15) fitness (VO2max of 37 vs 62 ml.min-1.kg-1). INTERVENTIONS:
      None. MEASURES: Each subject completed, in random order, a series of 12 min cycle
      ergometer exercise trials corresponding to 50, 60, 70 and 80% of VO2max. VO2,
      minute ventilation (MV), blood lactate (BL), rectal temperature (RT), heart rate
      and blood pressure were measured. RESULTS: There was a significant (p < 0.05)
      increase in the slow component of VO2 for each level of fitness across time and
      at each workrate. There were no between group differences for any variable. The
      increase in the slow component of VO2 ranged from 70 ml.min-1 for the lighter
      workrates to 543 ml.min-1 for the high fitness group at 80% of maximal VO2 (both
      p < 0.05). The oxygen cost of MV, RT and rate pressure product accounted for
      about 50% of the observed increase in the slow component of VO2. MV appears to
      increase in a pattern most similar to the slow component of VO2 and the oxygen
      cost of MV generally accounted for the highest percentage of the observed
      increase. CONCLUSIONS: The slow component of VO2 needs to be considered when
      prescribing exercise. These results are not conclusive concerning the primary
      mediators of the slow component of VO2.

PMID- 9763798
TI  - The Bruce treadmill protocol: does walking or running during the fourth stage
      alter oxygen consumption values?
AB  - OBJECTIVE: To investigate heart rate (HR) and relative oxygen consumption (VO2)
      measures during two modes (walking or running stages four) of the Bruce treadmill
      protocol. PARTICIPANTS: Male volunteers (n = 27), ranging in age from 25 to 56
      years (M = 39.1 +/- 10.7 yrs). EXPERIMENTAL DESIGN: S's performed to volitional
      fatigue on the two randomly assigned treadmill tests. MEASURES: HR and VO2 were
      taken each minute and at point of exhaustion. RESULTS: Dependent "t"-tests
      revealed a significantly (p < or = 0.05) difference between the protocols at 11
      minutes (running = 46.7 +/- 3.9 > walking = 44.6 +/- 3.7 ml[kg.min-1]) and at 12
      minutes (running = 49.3 +/- 4.1 > walking = 47.6 +/- 3.5 ml[kg.min-1]) on the VO2
      values. A significant differences was noted on HR at 11 minutes (running = 158.1
      +/- 13.5 > walking = 156.0 +/- 13.0 bpm) and at 12 minutes (running = 160.4 +/-
      11.0 > walking = 157.8 +/- 11.4 bpm) between the protocols. The two-way ANOVA
      technique revealed no significant differences or interactions on VO2 or HR
      between younger (< 45 yrs) and older (> or = 45 yrs) subjects during either
      protocol. A one-way ANCOVA indicated no significant differences between taller
      and shorter subjects on VO2 during the fourth stage of the Bruce protocol. The
      correlations, between the two protocols, for HR were strong but were weaker and
      inconsistent for VO2. The repeated measures ANOVA indicated significant within
      subject variability between test administrations. CONCLUSIONS: When testing
      endurance trained males, modality, age and height are not factors in differences
      of VO2 values during the 4th stage of the Bruce treadmill test but learning
      effect could be.

PMID- 9763799
TI  - Basal reproductive hormonal profiles are altered in endurance trained men.
AB  - OBJECTIVE: The purpose was to examine the basal reproductive hormonal profiles in
      age-matched groups of endurance trained (ET) and sedentary (SED) men under
      controlled conditions. EXPERIMENTAL DESIGN: Resting basal blood samples were
      obtained from groups of ET and SED men after a 24-hr control period. Blood
      specimens were analyzed for testosterone (T), free-testosterone (fT), sex-hormone
      binding globulin (SHBG), luteinizing hormone (LH), cortisol, and prolactin. The
      design of the study was retrospective and cross-sectional in nature. SETTING:
      Laboratory setting at the University of North Carolina, North Carolina USA.
      PARTICIPANTS: ET men (n = 53) who had been involved with chronic endurance
      exercise training for > or = 5 years. SED men (n = 35) were selected of
      comparable ages and the fact that they had done no formal exercise training.
      RESULTS: Results indicated that the basal T and fT of the ET men were
      significantly (p < 0.01) lower than that of the SED men. The levels of these
      hormones in the ET men where in the normal clinical range, but represented only
      55% to 85% of those seen in the SED men. For SHBG, LH, cortisol, and prolactin,
      no significant differences (p > 0.05) were found between the ET and SED men.
      CONCLUSIONS: ET men have lowered basal T and fT levels and this suppression may
      be related to an alteration in the hypothalamic-pituitary-testicular regulatory
      axis since the LH of the ET was not elevated. Whether these hormonal changes have
      any significant beneficial (i.e., protective cardiovascular) or negative (i.e.,
      decrease anabolic-androgenic processes) physiologic consequences remains to be
      determined.

PMID- 9763800
TI  - Alcohol use and behaviors in women long-distance race participants reporting a
      history of bulimia and/or anorexia nervosa.
AB  - OBJECTIVE: To describe the relationship between a reported a history of an eating
      disorder, a history of problem alcohol behavior and current alcohol consumption
      in women long-distance runners. DESIGN: Survey. SETTING: General community.
      PARTICIPANTS: Women participating in a 20-mile road race (n = 398) and age
      matched non-exercising women enrolled in a family practice health maintenance
      organization (n = 121) (mean age, 37.1 +/- 9.4 years). INTERVENTION: Not
      applicable. MEASURES: Responses to questions relating to 1) a past history of an
      eating disorder; 2) weight; 3) running and exercise habits; 4) drinking behaviors
      using alcoholism screening tests; 5) quantity-frequency data of the previous two
      week alcohol consumption. RESULTS: Ten percent of racers and 4.1% of controls
      reported a history of an eating disorder. Those racers reporting a history of
      bulimia nervosa without anorexia were more likely to report feeling guilty about
      their drinking, drunk-driving arrests, an elevated score on an alcoholism
      screening test (suggestive of problem drinking), alcoholism, and seeking help for
      problem drinking than other racers or the control population without a history of
      an eating disorder. However, bulimic racers did not report either increased
      current alcohol consumption or occasions of drinking, including binge drinking
      (five or more drinks in one episode). CONCLUSIONS: Women racers reporting a
      history of bulimia nervosa are more likely to report a history of problem
      behaviors with alcohol but not differences in current alcohol consumptions from
      that reported by other women racers or women without a history of an eating
      disorder from the control population.

PMID- 9763801
TI  - Cardiovascular fitness, physical activity and selected coronary heart disease
      risk factors in adults.
AB  - BACKGROUND: The aim was to investigate the associations between cardiovascular
      fitness and physical activity, and their relationship to selected coronary heart
      disease (CHD) risk factors. METHODS: This was a cross-sectional study for one
      week. All participants were Japanese living in the City of Toyota, Japan. Two
      hundred and twenty-two healthy Japanese (104 men and 118 women), with ages
      between 20 and 62 years old. Cardiovascular fitness (VO2max) was measured by a
      progressive submaximal bicycle ergometry test. Physical activity was estimated by
      an accelerometers attached to the subject's waist for one week, CHD risk factors
      included blood pressure, fasting levels of blood lipids, and apolipoprotein
      concentrations. RESULTS: Cardiovascular fitness and physical activity were
      positively related (r = 0.41 in men and 0.65 in women). For both genders, Pearson
      coefficients as well as age-adjusted partial correlations indicated that fitness
      was more closely linked to CHD risk factors than activity was. Also, CHD risk
      factors were analyzed by three groups of fitness and activity levels in both
      genders, which indicates that subjects who are physically fitter and/or more
      active tend to have better CHD risk profiles. CONCLUSIONS: As favorable CHD risk
      profile was related to cardiovascular fitness, but not to physical activity in
      both genders, it can be concluded that fitness may be a more important
      independent predictor for CHD risk factors than activity measured by
      accelerometer over one week.

PMID- 9763802
TI  - Prolonged exercise alters cardiac chronotropic responsiveness in endurance
      athletes.
AB  - OBJECTIVE: To determine whether exhaustive exercise alters cardiac adrenergic
      chronotropic responsiveness in endurance-trained athletes. METHODS: Fifteen
      athletes were studied prospectively 2-4 days before and within 3.3 hours after
      completing the Hawaii Ironman Triathlon (3.9 km swim, 180.2 km bike, 24.2 km
      run). Increasing intravenous boluses of isoproterenol were given until the rise
      in heart rate was > 30 bpm (n = 3-6 doses). A log dose heart rate response curve
      was constructed, and the dose required to increase heart rate by 15 and 25 bpm
      estimated. Left ventricular size and function were also assessed by
      echocardiography. RESULTS: After race finish, left ventricular volume (98 vs 83
      cc), ejection fraction (56 vs 46%) and diastolic filling (3.86 vs 3.12 edv/sec)
      were reduced (all p < 0.01). Resting heart rate rose from 54 +/- 7 bpm to 70 +/-
      10 bpm. The isoproterenol dose required to increase heart rate by 15 bpm rose
      from 0.6 to 1.7 micrograms by 25 bpm rose from 1.8 to 4.0 micrograms, both p <
      0.01. The linear relationship between change in heart rate and log isoproterenol
      dose was preserved. CONCLUSIONS: Cardiac chronotropic responsiveness is reduced
      following an Ironman triathlon.

PMID- 9763803
TI  - The electrocardiographic T wave changes in highly trained athletes during
      training. An old problem revisited.
AB  - OBJECTIVE: To evaluate the T-wave pattern alterations during vigorous training in
      elite athletes. SETTING: Institute of Sport Science in Rome and National Rowing
      Center in Piediluco, Italy. STUDY POPULATION: Nine male and 7 female rowers of
      the national team were examined prospectively at different times of their
      conditioning period. METHODS: All athletes underwent electrocardiography and
      echocardiography; the ecg was analyzed for QRS voltages and axis, T-wave pattern
      and QTc interval; from echocardiography the left ventricular (LV) cavity
      dimension, wall thickness and mass were calculated. From Doppler-echocardiography
      the transmitral diastolic LV filling pattern was evaluated. RESULTS: Variation of
      T-wave voltages was seen in all the athletes. Specifically, during the low
      intensity training period the T-wave pattern was positive and increased in
      voltage (T-wave max amplitude in V6 increased to 130% in male and 100% in female
      than pretraining values). During the peak training a variety of patterns was
      observed, and a transient flattening was present in 50% of subjects. No
      concomitant alteration of heart rate, QRS and T-wave axis and QTc duration were
      observed. No significant changes of cavity dimension, wall thickness, LV mass
      index and Doppler-derived diastolic peak flow velocities were detected during the
      study period. CONCLUSIONS: Transient changes of T-wave pattern may occur in
      athletes as an effect of athletic conditioning, without changes of cardiac
      dimension or alteration of indexes of LV function. This finding supports the role
      of ecg monitoring to follow-up the individual athletes response to training
      exercise load.

PMID- 9763804
TI  - Reliability of isokinetic knee extension and flexion strength testing in elderly
      women.
AB  - BACKGROUND: Intertrial and test-retest reliability of isokinetic knee extension
      and flexion strength measurements was studied in eighteen elderly women (mean age
      68 +/- 5 yrs), using increasing and decreasing angular velocity testing
      procedures. METHODS:  EXPERIMENTAL DESIGN: five reciprocal knee extensions and
      flexions at three different angular velocities (90, 120, and 180 deg/sec) were
      performed by means of a MERAC apparatus on two occasions fifteen days apart.
      MEASURES: Data relative to torque, power and work were considered. RESULTS:
      Statistically significant differences were found often among the five trials and
      intraclass correlation coefficients, ranging from 0.03 to 0.90 for extensor
      muscles; ranging from 0.44 to 0.89 for flexor muscles, were shown among the best
      three outputs. Peak values were reached within the first three repetitions,
      though a 20% chance to produce peak outputs was shown in the last two
      repetitions. Increasing and decreasing test velocity procedures did not
      consistently show statistically significance for peak outputs. Generally, for
      each isokinetic parameter higher and more frequently significant correlation
      coefficients between test and retest experimental sessions were found for peak
      values (ranging from 0.36 to 0.80) with respect to mean values (ranging from 0.22
      to 0.74). CONCLUSIONS: These data suggest that a test procedure including five
      trials tends to increase the chance of producing the best peak outputs.
      Furthermore, considering the best peak and mean performances could be more
      appropriate when studying elderly women.

PMID- 9763805
TI  - Recurrent rhabdomyolysis associated with influenza-like illness in a weight
      lifter.
AB  - OBJECTIVE: This report describes a unique case of recurring rhabdomyolysis
      associated with influenza-like illness. PATIENT: A 16-year-old black male, a
      physically fit weight-lifter, presented complaining of a brief history of upper
      respiratory infection. He had experienced muscular aches and observed his urine
      was a brown "Coca Cola" color. He was diagnosed with an influenza-like illness
      and associated rhabdomyolysis. He had been previously treated for a similar
      episode of flu-like symptoms and brown urine two years before. The patient was
      treated with IV fluids and discharged on day seven. He has remained asymptomatic.
      Post-discharge muscle biopsy results indicated a partial deficiency of carnitine
      palmitoyltransferase II, a rare defect in mitochondrial metabolism. DISCUSSION:
      Although traumatic rhabdomyolysis cases have been reported, few case reports have
      been documented associating an influenza-like illness and rhabdomyolysis.
      Deficiency of carnitine palmitoyltransferase often causes nonexercise-induced
      rhabdomyolysis. CONCLUSION: Prevention should consist and a yearly influenza
      vaccination education on nutrition and exercise.

PMID- 9763806
TI  - [Neuroleptanalgesia in patients undergoing percutaneous, ultrasound-directed
      radiofrequency for primary or secondary, single or multiple hepatic neoplasms].
AB  - BACKGROUND: The use of percutaneous ultrasound-directed radiofrequency is a
      recent technique in non-surgical therapy of some neoplastic liver lesions.
      Purpose of this study is to demonstrate that the use of a narcosis-free analgesia
      allows to perform this procedure, which is generally painful and badly by the
      patient. METHODS: We treated 51 patients for a total of 126 procedures; the first
      17 patients underwent a mono- or multipolar technique with uncooled electrodes,
      while the remaining 34 patients have been treated with double perfusion lumen
      electrodes with the chance of tipcooling. We used diidrobenzoperydol and fentanyl
      with a mean dose for each session of 209 micrograms for the first 17 patients and
      109 micrograms for the other 34. RESULTS: Using VAS, we obtained a painless
      procedure in 42 patients and mild-pain sensations in 9 patients, while one hour
      after the procedure painless or light-pain sensation were observed in 49 patients
      and mild-pain in 2 patients, which required the use of FANS i.v. At discharge,
      all patients were pain-free or with very light pain sensation. We reduced the
      intra-hospital observation of patients from 5 to 3 hours, once the technique has
      been modified. 4 patients complained about nausea and 1 of these emesis. We did
      not observe any cardiovascular, respiratory and/or neurological complications.
      CONCLUSIONS: The use of neuroleptanalgesia allowed us to perform the described
      procedure with a good feeling by the patients.

PMID- 9763807
TI  - [Mathematical model for the predictive value of a test in critically ill patients
      studies according to APACHE II score and pathology at admission].
AB  - OBJECTIVE: To find a predictive model for mortality at four different days from
      the admission for critically ill patients. DESIGN: Retrospective study on two
      consecutive series of critically ill patients admitted in ICU. SUBJECTS: 1254
      critically ill patients, subdivided into two series of 813 (561 survivors and 252
      non survivors) and 441 patients (291 survivors and 150 non survivors),
      respectively. INTERVENTIONS: None. MEASUREMENTS: All patients had APACHE II
      calculated within the first 24 hours from the admission in ICU and, if the
      patient was still in ICU, also at the 5th, 10th and 15th day from the admission.
      Casistics was subdivided into two unequal series, ratio 2:1, with a random
      selection made on each of the 6 considered years. On the 1st series, in 1st, 5th,
      10th and 15th day, for mathematical predictive models were made, using stepwise
      logistic regression (BMDP, Los Angeles). In the 1st day the following independent
      variables were utilized: APACHE II score, the specific diagnosis at admission,
      fitted following Knaus' diagnostic criteria, united in 6 principal categories,
      while for the other 3 days the variation % of APACE II score as regards the
      previous day. RESULTS: For each of the considered day four mathematical models
      have been made. These models have been validated in both series in calibration
      from the Hosmer-Lemeshow Goodness-of-fit test and in discrimination from the ROC
      curves. For each day Y (Prob.% to die) = eLogit/1 + eLogit, where Logit = beta 0
      (constant) + beta 1*APACHE II + beta 2*Variat.%APACE II (difference between
      actual APACHE II - APACHE II of the previous day/actual APACHE II) + beta k,
      (coefficient pertinent to pathology). CONCLUSIONS: The mathematical model, as
      other models do, stratifies enough the casistics according to the risk of death.
      Waiting for further studies to make more precise prognostic mathematical models,
      this one and others can help the clinical assessment in single patient
      evaluation.

PMID- 9763808
TI  - [Morphologic and biochemical kinetics of the pathogenesis of acute lung injury by
      endotoxin in rats].
AB  - BACKGROUND AND AIM: To highlight the intervention sequence of cells and their
      products (RO degree and NO) involved in the pathogenesis of lung injury caused by
      the instillation of endotoxin in rats. EXPERIMENTAL DESIGN: An experimental
      comparative study in rats. MATERIALS AND METHODS: The experiments were performed
      using intratracheal instillation of endotoxin in rats (5 mg/kg in 0.125 ml of
      saline solution). Untreated rats or those instilled with saline solution alone
      formed the control group. All animals were sacrificed 12, 24 and 48 hours after
      instillation and the following studies were performed on both lungs: 1)
      morphological study (optical and electronic); 2) assay of lung MDA; 3) NADPH
      diaphorase evaluation using a histochemical method. RESULTS: Lung damage evolves
      gradually over 48 hours. After the first 12 hours, neutrophil granulocytes were
      present in the lung capillaries together with monocytes; monocytes were also
      present in the interstitium. During the following hours, monocytes differentiated
      into macrophages and, once activated, the granulocytes passed into the
      interstitium. The parenchyma appears to be extensively altered. Tissular MDA
      gradually increases until it reaches a maximum level (p < 0.01 vs basal) at 48
      hours. Positivity for NADPH-d in macrophage and/or fibroblastic cells was evident
      after 24 hours and increased after 48 hours. CONCLUSIONS: Acute lung injury
      caused by endotoxin involves both NO and RO degree. Their production is related
      to different cell types and follows slightly different kinetic.

PMID- 9763809
TI  - [The effects of a dose of epidural clonidine combined with intrathecal morphine
      for postoperative analgesia].
AB  - OBJECTIVE: To evaluate the effectiveness of a single bolus of epidural (ED)
      clonidine (C) associated with intrathecal morphine (M) on postoperative analgesia
      after cesarean section (CS). DESIGN: Prospective double-blind randomized study.
      SETTING: Obstetric department. PATIENTS: Fourty patients ASA 1-2 submitted to
      combined spinal-epidural block (CSE) for CS. INTERVENTIONS: A needle through
      needle set for CSE was used. The intrathecal block was induced with 2.7-3 ml of
      isobaric 0.5% bupivacaine (B) and 250 micrograms of M. After ED test with 0.5% B,
      a single bolus of C 150 micrograms in NS 10 ml (group C, n 20) or NS 10 ml as
      placebo (group P, n 20) was given through the ED catheter. METHODS: The
      observation for 36 hours evaluated analgesia (VAS until the first dose of
      additional analgesic, total amount of analgesic and time of first analgesic
      request) and side effects (variations of arterial pressure and heart rate, motor
      block, sedation, nausea, vomiting, itching, respiratory depression). Groups were
      statistically compared. RESULTS: In group C lower analgesic request
      (significantly between 12th and 18th hour) and significant delay of first request
      (22.5 +/- 4.1 h) were registered. VAS showed significant trend to opposite sign
      variations (downwards in group C, upwards in group P) at 1, 2 and 12 hours. In
      group C lower sistolic arterial pressure at 1 and 4 hours, denser motor block at
      2 and 4 hours and mild sedation were observed. CONCLUSIONS: A single ED bolus of
      C 150 micrograms after CS significantly enhances and prolongs the analgesic
      effect of M 250 micrograms without important side effects.

PMID- 9763810
TI  - Inhaled nitric oxide during anesthesia for bilateral single lung transplantation.
      Case report.
AB  - Recently inhaled nitric oxide (iNO) has been used as pulmonary vasodilator
      without any effect on systemic hemodynamics. iNO has been also used in cardiac
      and thoracic surgery, involving lung transplantation. In this case report a
      patient, 41 years old female, affected by bronchiectasis, underwent bilateral
      sequential single lung transplantation and during one lung ventilation and
      pulmonary artery clamped iNO allowed to avoid cardiopulmonary bypass and to carry
      out the procedure successfully.

PMID- 9763811
TI  - Unexpected cardiac arrest during epidural anaesthesia.
AB  - We reported the case of sudden asystole requiring close chest cardiac massage in
      a 56-yrs-old health man receiving epidural anaesthesia for elective transurethral
      resection of bladder tumour (TURBT). The anaesthetic procedure was performed in a
      regional-block-room. Cardiac arrest developed few minutes after local anaesthetic
      injection, before the patient has been transferred to the operating room. The
      importance of patient monitoring during regional anaesthesia must be further on
      pointed out, especially when the anaesthetic procedure is performed out of the
      operating room (e.g. in the recovery room or in a "regional-block-room").

PMID- 9763812
TI  - [Prevention of obstetrical damage to the perineum. Proposal for a fetal-pelvic
      index for the selection of parturients at risk].
AB  - BACKGROUND: According to some authors, vaginal delivery always causes denervation
      of perineum and the greater the damage the longer the second labour phase (the so
      called "delivering phase"). Therefore, it is necessary to reduce the number of
      too prolonged labours, but it is equally important to avoid an uncontrolled
      increase of cesarean sections. In order to achieve this objective, it is
      important to carry out a careful selection among laboring women and choose those
      most at risk for whom cesarean section is strongly recommended. On the basis of
      the data collected by the medical literature and in consideration of the
      pathogenetic role of the outlet dystocia, we have tried to identify a simple and
      effective prognostic index resulting from the different pelvimetric and
      ultrasonographic parameters. METHODS: In 72 full-term pregnant women, we have
      taken into account the ultrasonographic parameters expressing the fetal dimension
      (cephalic diameters, cephalic and abdominal circumferences, estimated fetal
      weight according to Haddlok), the outlet pelvic diameters (trans-ischial and
      coccygeal-pubic) and a fetal-pelvic index derived from these parameters. RESULTS:
      If taken individually, these parameters do not seem to have any direct connection
      with the length of the delivering phase, but the combination of the cephalic and
      external pelvimetric diameters has produced a significative statistical
      coefficient. CONCLUSIONS: On the basis of the data collected, it is suggested
      that a careful evaluation of external pelvimetric and cephalic parameters would
      be useful from the clinical point of view.

PMID- 9763813
TI  - [Predictive factors of fetal macrosomia].
AB  - BACKGROUND: Fetal macrosomia is a condition which may increase the risk of
      mechanical and/or dynamic problems for the parturient. In the past, we have
      demonstrated that in more than half of the cases it is not possible to exclude a
      contribution of maternal pathology to the determination of fetal-macrosomia. The
      aim of this work is to verify whether our more recent experience regarding
      predictive factors of fetal macrosomia shows some noteworthy novelty. METHODS:
      The study was retrospectively carried out on pregnant women who, during the
      period January 1994-February 1996, delivered babies weighing at least 4 kg at the
      Midwifery School of Camerino. With regard to the frequency of the main risk
      factors of fetal macrosomia described in scientific literature, the sample was
      compared with a control group randomly selected. RESULTS: Advanced gestational
      age at the time of delivery, parental tallness, maternal overweight/obesity,
      gestational glucidic dysmetabolism, a distance between pubis and uterine fundus
      of at least 34 cm, male sex of the unborn child have proved to be predictive
      factors of fetal macrosomia. CONCLUSIONS: The differences in comparison with the
      past, on the other hand altogether negligible, are the consequence of changes in
      the management of some obstetric situations.

PMID- 9763814
TI  - [Use of intrauterine device by nulliparous women. Prospective study and
      preliminary data].
AB  - BACKGROUND: The aim of the study, that is still on the way, was to evaluate the
      negative effects of an intrauterine device, used for more than 2 years, on future
      fertility of young women who due to medical or personal reasons couldn't use
      hormonal contraceptives. METHODS: A prospective study was started in 1987 in a
      group of 515 nulliparous healthy women (age 20-30) using an intrauterine device
      (Nova T, Schering, Multiload Cu 275 Organon) as contraceptive method. Two hundred
      and twentyfour women wished to become pregnant following the IUD extraction.
      RESULTS: Within 12 months, 221 (98.7%) of them became pregnant demonstrating the
      harmlessness of the contraceptive method on future fertility. All pregnancies had
      a normal course, except one abortion at the 8th week of gestational age. There
      hadn't been pregnancies during the observation period, 25 (4.8%) women requested
      the IUD be removed before the end of the study because of side effects.
      DISCUSSION: IUD did not cause a reduction in fertility or an increase in ectopic
      pregnancy in our group of patient.

PMID- 9763815
TI  - [Psychological consequences in women with symptomatic HPV infection].
AB  - OBJECTIVE: Evaluation of psychological and social aspects of women with diagnosed
      genital HPV-infection. EXPERIMENTAL DESIGN: A retrospective study of 40 women
      with a diagnosis of HPV-genital infection has been made. INTERVENTIONS AND
      MEASURES: A questionnaire for gathering information on social life, sexuality and
      emotional relationship with the partner was submitted to the patients. RESULTS:
      There is a high percentage of sexual impairments after diagnosis of HPV
      infection. CONCLUSIONS: HPV infections, as many genital pathologies, lead to
      problems with sexuality as well as hypochondriac fears.

PMID- 9763816
TI  - [The ICSI (Intracytoplasmic Sperm Injection)].
AB  - ICSI (Intracytoplasmic Sperm Injection) is the latest known assisted reproduction
      technique (ART) and it already appears to be mature. In fact the analysis of the
      results presented by the researchers over the years has shown that the most
      specific indication for this ART is the sterility of the couple with serious male
      pathology, up to ejaculatory azoospermia where it is possible to perform MESA,
      PESA or TESE. Any kind of sterility could be solved with ICSI whose only limit
      presently known is the high technology and therefore high costs involved. The
      percentage of oocytes that undergo ICSI without being damaged varies from 87% to
      94% and the percentage of fertilization varies from 33% to 71%. The transfer rate
      is 59-100%. The rate of pregnancies per couple ranges from 12% to 40% of the
      couples, from 11% to 41% for the transfers. Since abortions are similar to the
      values of the normal population (10-15%), ICSI is actually the assisted
      fertilization technique with the highest incidence of pregnancies and "take home
      babies". The percentage incidence of the two sexes, of the malformations and the
      typologies of malformations corresponds to those observed in the population with
      spontaneous pregnancies. Since there is no natural selection of the gametes in
      ICSI, one may be sure that when spermatozoa with any kind of pathology are
      injected, the pregnancy does not take place at all.

PMID- 9763817
TI  - [Hereditary renal agenesis . Report of a case].
AB  - Renal agenesis is thought to result from a lack of induction of the metanephric
      blastema by the ureteral bud. Bilateral renal agenesis/dysgenesis (BRA/D) is
      rare, occurring in only one or two per 10,000 births. Despite its being moreover
      a sporadic event, there is a male to female ratio of 2.5 to 1 and approximately
      20-36% of BRA/D present a familial recurrence, for genetic transmission most
      probably autosomal dominant with incomplete penetrance and variable expression,
      termed hereditary renal adysplasia (HRA). A case of prenatal diagnosis by
      ultrasound of renal agenesis/dysgenesis (left renal agenesis and severe right
      multicystic dysplastic kidney) is described here. A woman in the 32nd week of
      pregnancy, who has never undergone any clinical and medical examination, presents
      at the ultrasound control. A male fetus was born from breech delivery at 34 weeks
      gestation, weighted 1950 g died after two hours because of severe pulmonary
      hypoplasia. Autopsy confirmed the antenatal diagnosis of left renal agenesis and
      right multicystic dysplastic kidney, that measured 42 x 31 x 25 mm, with
      bilateral complete absence of ureters and renal vessels. No other malformations
      were present. The infant's chromosomes were normal (46 XY). No specific
      chromosomal anomaly was identified in either parents. Both the parents had normal
      genitourinary ultrasound findings. In the wife's family pedigree, a sibling had
      asymptomatic unilateral renal agenesis, found at ultrasonography, and one
      maternal aunt had unilateral multicystic kidney and bicornuate uterus. Moreover
      one maternal uncle died at birth after preterm delivery from respiratory failure,
      unfortunately kidneys were never examined. Instead, no renal anomaly was
      identified in the husband's family history. The parents must be made aware not
      only of the inevitable fatal outcome for the fetus but also of the increased risk
      of recurrence in a subsequent pregnancy. On the basis of the literature, (of
      which this case is a further confirmation) it is underlined the necessity that
      all families of bilateral renal agenesis/dysgenesis patients-should have a
      detailed evaluation, including a detailed family history and ultrasound study of
      the kidneys and uterus; in fact all first-degree relatives have an increased risk
      of having silent genitourinary malformations.

PMID- 9763818
TI  - [The role of chorionic gonadotropin in transient hyperthyroidism in hyperemesis
      gravidarum].
AB  - A possible association of hyperemesis gravidarum with biochemical transient
      hyperthyroidism (a significant self-limited increase in serum levels of some
      thyroid hormones) has long been reported. It seems there is not any causal
      connection between the two above mentioned conditions, but they may be both
      independently related to the same cause: the trophoblastic production of a large
      amount of human chorionic gonadotropin or, otherwise, the presence in the
      maternal circulation of structural variants of hCG with higher biological
      activity. The validity of such hypothesis, denied by some authors, encounters the
      verification in the peculiar clinical case described in this report. It also
      shows clearly the danger of considering a case of hyperemesis gravidarum as of
      psychological nature, without having preliminarily excluded an organic cause. For
      the pregnant woman, to hear of her unconscious refusal of pregnancy or of the
      timeliness of her removal from the environment in which some conflictual
      situations have likely raised or, furthermore, to hear of other common places
      often too easily evoked could be cause of anxiety and unjustified feelings of
      guilt.

PMID- 9763819
TI  - [The role of vaginal pH. Importance of its normalization in the prevention of
      recurrent vaginitis].
AB  - BACKGROUND: A sample of 100 women was clinically examined for a very various
      vulvovaginal symptomatology and an individual diagnosis of vulvovaginitis of
      different aetiology was established. METHODS: All women were treated with
      antibiotic and/or antimycotic drugs on the basis of individual diagnosis. Sixty
      women had only this treatment, while 40 women had also a supplementary treatment
      with a cleanser emulsion characterized by physiologic pH value and an antiseptic
      activity due to a vegetable extract (Saugella Attiva, Lab. Guieu). The
      symptomatologic changes due to the two treatments were compared. RESULTS AND
      CONCLUSIONS: Combined treatment (drug + antiseptic) obtained better results
      mostly in subjective symptomatology; this combined treatment was very useful in
      the recovery of the Doderlein population.

PMID- 9763820
TI  - [Pregnancy today. Randomized study of the emotional state of the woman and her
      partner].
AB  - BACKGROUND: Pregnancy is a remarkable ground for studying the biopsychosocial
      perspective of psychosomatics, because there is a close correlation between
      biological conditions, that quickly change in time, and emotional implications
      that are this result of women psychological structure, her psychosexual
      maturation degree and her social and environment past and present influences.
      METHODS: Through a questionnaire including some general data and a more specific
      section to evaluate psychic and emotional factors of the pregnant and her partner
      during pregnancy, we interviewed 100 pregnant women beginning from the 32nd
      pregnancy week; all women attended the psychoprophylactic lessons for childbirth,
      they were between 20 and 41 years old and the 87% was primipara and the 13% was
      multipara. RESULTS AND CONCLUSIONS: This study showed that even if pregnancy is
      more and more planned and desired, anxiety and fears follow the joy and the
      happiness of having child, both in man and in woman. Thus, pregnancy and birth,
      seem to be, also today, too much medicated to the detriment of the "naturalness"
      of the event: in fact, woman uptake more drugs and there is an increased need to
      have a good medical assistance not for real obstetrical problems but only to make
      up for intense anxiety.

PMID- 9763821
TI  - Collective bargaining is inevitable for physicians.

PMID- 9763822
TI  - 1998 statutory changes affecting controlled substances.

PMID- 9763823
TI  - Emergency medicine quiz.

PMID- 9763824
TI  - Case report of long-term survival in a patient with acquired immunodeficiency
      syndrome and cryptococcal meningitis.
AB  - In the era before protease inhibitors were available, the great majority of
      patients with AIDS died within five years of the diagnosis. This grim reputation
      may cause both physician and patient to give up hope prematurely when
      antiretroviral therapy fails. We report a patient who survived five years after
      the diagnosis of cryptococcal meningitis and AIDS. Although there are now
      combinations of antiretroviral drugs available that can delay disease progression
      and extend the lives of AIDS patients, these are associated with a significant
      failure rate. It is thus important to be aware of the potential to extend life in
      patients even when antiretroviral therapy is not effective.

PMID- 9763825
TI  - [A painful inflammation of the thyroid].
AB  - Four women aged 30, 29, 52 and 43 years presented with what appeared to be
      subacute thyroiditis (De Quervain's thyroiditis). This disease is characterized
      by fatigue, a painful thyroid gland and thyrotoxic manifestations. The diagnosis
      is further based on a high erythrocyte sedimentation rate and low tracer uptake
      during thyroid scintigraphy. Only the first patient showed a typical course. In
      the second and third ones the painful thyroid was associated with nodular
      enlargement. Fine needle aspiration cytology was at first consistent with
      subacute thyroiditis but a repeated aspiration showed papillary carcinoma in the
      second and anaplastic carcinoma in the third patient. In the fourth one, subacute
      thyroiditis was accompanied by normochromic anaemia, a low serum albumin
      concentration and liver function disorders. She made a full recovery without
      treatment. Thyroid malignancies can mimic subacute thyroiditis. Persistent
      nodular enlargement of the thyroid is suspicious and requires careful
      investigation.

PMID- 9763826
TI  - [Appearances deceive in investigations of cancer clusters].
AB  - Many a doctor from time to time encounters people concerned about environmental
      causes of disease, whom he or she cannot answer properly because of lack of
      knowledge concerning the effects of chemical or physical exposure of the human
      body (nuclear plants, environmental pollution, electromagnetic radiation).
      Usually post hoc cluster investigation is very unrewarding especially when there
      is no clearcut hypothesis or evidence of a causal relation, and when the relative
      risk is well below 8. From an epidemiological point of view it is surprising that
      an unexpectedly low frequency of a certain disease in a particular region does
      not attract this kind of attention. Concerned people will most probably benefit
      more from risk communication by environmental epidemiologists than from cluster
      investigation or extensive case-control studies ('fishing expeditions') in case
      little is known of the etiology.

PMID- 9763827
TI  - [Health Council Report 'Radiofrequency electromagnetic fields (300 Hz-300 GHz).
      The Health Council of the Netherlands].
AB  - The Health Council of the Netherlands in 1997 issued a report updating the
      guidelines for maximum acceptable exposure to radiofrequency electromagnetic
      fields formulated in 1975. The new recommendations are based on thermal effects
      for frequencies over 10 MHz. The committee considers the results of studies
      indicating non-thermal effects such as direct damage to DNA, not reliable enough
      to be used in setting exposure limits. Electromagnetic interference by
      electromagnetic fields generated by hand-held telephones may indirectly result in
      threats to health if vital medical equipment is affected. The committee advises
      people wearing an implanted pacemaker not to carry a portable telephone that is
      in stand-by mode in close proximity to the pacemaker; a minimum distance of 15 cm
      should be observed.

PMID- 9763828
TI  - [Mycophenolic acid: a welcome adjunct immunosuppressant after organ transplants].
AB  - Three major double-blind trials in kidney transplantation patients have shown
      that mycophenolic acid (mycophenolate mofetil), added to an immunosuppressive
      regimen consisting of cyclosporine and prednisone, reduces the incidence of acute
      rejection after kidney transplantation by 50%, during the first six months. This
      statistically significant reduction is achieved equally with daily doses of 2 or
      of 3 g. In view of the fact that the side effects (diarrhoea, abdominal cramps,
      leukopenia) are more frequently found in the patients treated with 3 g, it is
      advised to prescribe 2 g mycophenolic acid. As acute rejection is a risk factor
      for the development of chronic rejection and because a beneficial effect of
      mycophenolic acid on chronic rejection in animal models has been observed, there
      may also be an effect on late graft loss due to chronic rejection after kidney
      transplantation in man.

PMID- 9763829
TI  - [Straying in the methodology. I. Introduction].
AB  - In recent decades clinical studies with patients have gained qualitative and
      quantitative importance. This has led to growing interest in methodological
      quality. At present, doctors need more methodological knowledge. Sophisticated
      software enables almost everyone to carry out the most exotic of statistical and
      epidemiological analyses, but the methodological implications are too often
      incompletely understood. In a series of column-like short articles methodological
      items will be discussed, in order to point out frequent errors, fallacies and
      practical problems.

PMID- 9763830
TI  - [Straying in the methodology. II. Bias introduced by questionnaires].
AB  - Some characteristics of self-report questionnaires can result in bias in
      responding. When a test item or a questionnaire is biased, the observed scores
      form an imprecise measurement of reality as a consequence of systematic errors of
      measurement. Causes of such bias are: unclear instructions, vague wording of the
      test items, culture-bound item content, suggestive questions, framing of
      questions, social desirability of certain answers, faking good, faking bad and
      the recall bias.

PMID- 9763831
TI  - [No increase in cancer incidence due to high-voltage cables in Odijk].
AB  - OBJECTIVE: To determine the incidence of cancer in Odijk and the connection if
      any of the occurrence of cancer with the presence of a high-voltage cable
      constructed there in the fifties. DESIGN: Descriptive. SETTING: Public Health
      Services, South-East Utrecht, the Netherlands. METHOD: Data on the numbers of new
      cancer patients in Odijk over the period 1985/'96 were obtained from general
      practitioners, from the Integral Cancer Centre Mid-Netherlands (IKMN) and from
      the Foundation Dutch Study Group Leukaemia in Children. The classifications were
      according to age and to distance from the home to the high-voltage cable. The
      electric and magnetic field strengths in dwellings situated less than 28 m from
      the cable were calculated. RESULTS: Cancer was diagnosed in 131 patients in the
      period 1985/'96, 127 adults and four children. The cases in 3 of 4 children
      occurred in the period 1993/'96. Over the period 1990-1994, the registered cancer
      incidence did not deviate from the expected incidence in the IKMN region, nor
      from the mean incidence in the Netherlands. Neither for adults nor for children
      was a relationship found between cancer and living in the vicinity of the high
      voltage cable. The exposure to the electric field of persons living in houses
      near the cable was maximally 7%, and exposure to the magnetic field maximally
      6.5% of the maximal liminal values applied in the Netherlands on recommendation
      of the Health Council. CONCLUSION: No relationship existed between development of
      cancer and the presence of a high-voltage cable.

PMID- 9763832
TI  - [The treatment of basal cell carcinoma patients by dermatologists in Netherland].
AB  - OBJECTIVE: To determine the policy of dermatologists practising in the
      Netherlands in the treatment of basal cell carcinoma. DESIGN: Written enquiry.
      SETTING: Catharina Hospital, Eindhoven, the Netherlands. METHOD: All 293
      dermatologists practising in the Netherlands were sent a questionnaire in May
      1996 containing 15 questions about diagnosis and treatment of basal cell
      carcinoma. RESULTS: Eighteen forms dropped off because of termination of the
      practice or joint completion in group practices. The response was 76% (208/275).
      The diagnosis was made usually on the basis of histological examination (71% of
      the respondents; 84% in a tumour recurrence). Excision was the preferred
      treatment for all subtypes of basal cell carcinoma; second choices were
      cryosurgery or curettage/electrocoagulation. Roentgen contact therapy has been
      practically abandoned. New methods such as photodynamic therapy and immunotherapy
      are being used only sporadically on an experimental basis. Most dermatologists
      regarded tumour recurrences as a bigger problem than primary tumours. They
      attempt to reduce the percentage of recurrences by giving advice about risk
      factors (sunlight). CONCLUSION: Too little use is being made of diagnostic biopsy
      to enable an optimal choice of therapy of basal cell carcinomas, especially in
      cases of recurrence tumours.

PMID- 9763833
TI  - [A severe anaphylactic shock caused by spraying the oak processionary caterpillar
      (Thaumetopoea processionea) in North Brabant].
AB  - The processionary caterpillar, Thaumetopoea processionea, caused much
      inconvenience in the Netherlands in 1996-1997; from the medical point of view,
      mostly itching and skin rash. After contact with stinging bristles of the
      caterpillar and with the pesticide Dimilin SC-48, of which diflubenzurone is the
      active agent, a 72-year-old man had to be resuscitated because of ventricular
      fibrillation caused by hypotension related to relative underfilling and low
      systemic vascular resistance. He made a good recovery. Such life-threatening
      situations can be prevented by publicly announcing plague control measures and
      closing of the affected areas to the population, with ample margins.

PMID- 9763834
TI  - [Two children with a rare etiology of torticollis: primitive neuro-ectodermal
      tumor and Grisel's syndrome].

PMID- 9763835
TI  - [Children who cough and wheeze: relief of symptoms after parents stop smoking].

PMID- 9763836
TI  - [Kindler syndrome].

PMID- 9763837
TI  - [The hyperglycemic dehydration syndrome].
AB  - Two patients, men aged 47 and 64 years, were found in a comatose condition in
      their homes, after a period of fatigue, polyuria and polydipsia. They had not
      been known to suffer from diabetes mellitus, but now displayed a hyperglycaemic
      hyperosmolar non-ketoacidotic disorder as the first manifestation of diabetes
      mellitus type 2. In that condition, just sufficient insulin is present to
      counteract ketone production, but not enough to prevent hyperglycaemia.
      Neurological and thromboembolic manifestations, possibly fatal, may result from
      severe dehydration brought about by a vicious circle in which osmotic diuresis
      reduces the effective circulating volume, causing renal function to decrease and
      hyperglycaemia to increase even more. Both patients recovered fully after
      adequate treatment with solutions of NaCl and glucose.

PMID- 9763838
TI  - [How much mental illness is there in the Netherlands?].
AB  - According to the results of recent epidemiological studies, over 3 million of the
      people in the Netherlands per year are supposed to suffer from severe mental
      disorders. This high prevalence should be regarded in connection with the
      diagnostic criteria and interview techniques applied. The final results of such
      epidemiological studies depend on where one draws the dividing line between
      clinically relevant mental disorders and normal problems of life.

PMID- 9763839
TI  - [The risk of a multiple myeloma in patients with paraproteinemia: a myeloma risk
      score developed in the region of the Comprehensive Cancer Center West].
AB  - Diagnoses in patients with paraproteinaemia are diverse; few (mostly single
      centre based) studies are known that describe incidence, diagnoses and follow-up
      in patients with paraproteinaemia. In the region of the Comprehensive Cancer
      Centre West in the Netherlands (population 1.6 million, 1992) a population-based
      registry was set up in the period 1991-1993. Patients (n = 1464; median age: 72
      years; range: 16-102) were entered by clinical chemists, internists,
      haematologists, and pathologists. Multiple myeloma and plasmacytoma were
      diagnosed in 261 patients (18%), paraprotein-related haematological diseases in
      159 patients (11%) and paraprotein-related internal diseases in 210 patients
      (14%). After bone marrow examination monoclonal gammopathy of unknown
      significance (MGUS) was diagnosed in 207 (14%) patients. No further diagnosis
      could be made in 627 (43%) patients mostly for lack of supplementary bone marrow
      and (or) X-ray examinations. Consequently, more than two-thirds of all patients
      with a newly found paraprotein did not show any sign of a haematological
      malignancy. Using these data a 'myeloma risk score' was developed to predict the
      presence of a multiple myeloma based on paraprotein type and concentration,
      aiding the physician in determining which patients should undergo further bone
      marrow and skeletal examinations.

PMID- 9763840
TI  - [Multiple myeloma; treatment in the year 1998].
AB  - There are a number of studies dealing with intensive chemotherapy and stem cell
      transplantation in multiple myeloma. As to autologous transplantation best
      results have been obtained with younger patients (below 60 years) who had
      responsive disease and received their transplant within one year after start of
      treatment. Unfavourable prognostic factors were a high beta 2-microglobulin level
      and abnormal cytogenetics including any translocation or chromosome 11/13
      abnormalities. Only one phase III study has been published, indicating a
      favourable effect of autologous transplantation. Despite the existence of a so
      called 'graft-versus-myeloma effect' the overall outcome of patients after
      allogeneic transplantation is not better than after autologous transplantation,
      probably due to the inclusion in the published studies of heavily pretreated and
      refractory patients responsible for a high treatment related mortality. The
      ultimate value of intensive treatment of multiple myeloma will become clear in
      the coming years when more data become available from current phase III studies
      including the Dutch HOVON multicentre trial in which conventional treatment is
      compared with intensified therapy including bone marrow ablation and autologous
      stem cell transplantation.

PMID- 9763841
TI  - [Acute urinary retention in women].
AB  - Acute urinary retention in women is not a common problem. The incidence is 0.07
      per 1000 inhabitants per year. The causes of acute urinary retention can be
      divided into four groups: obstructive, neurological, pharmacological and
      psychogenic. More than half of acute urinary retentions occur after surgery or
      parturition. The most common obstructive cause is a gynaecologic tumor. A
      psychogenic cause is a diagnosis per exclusionem. The treatment of the acute
      urinary retention has to be catheterisation before further investigation is done.

PMID- 9763842
TI  - [The cost of sickness in the Netherlands in 1994; the main determinants were
      advanced age and disabling conditions].
AB  - OBJECTIVE: To estimate the costs of health care in 1994, the development of the
      costs assigned to specific diseases, and the future costs. DESIGN: Descriptive.
      SETTING: Erasmus University, Department of Public Health, Rotterdam, the
      Netherlands. METHOD: For each health care sector, costs were allocated to 62
      diagnostic groups, age and sex making maximal use of national registries and
      other sources with data on health care use in the Netherlands. RESULTS: More than
      80% of the 60 billion Dutch guilders that were spent on health care in 1994 could
      be assigned to specific diseases. Most costs were made for non-fatal diseases
      like mental deficiency, dementia and musculoskeletal disease. Except for
      cardiovascular disease, the share of major causes of death in the total costs was
      not significant. Average costs per inhabitant were low during youth and adulthood
      but increased exponentially with age from age 50 onwards. Between 1988 en 1994,
      health care costs experienced an annual growth rate of 5.2%, caused by price and
      wage increases (one half), ageing (a quarter) and other effects on health care
      costs such as epidemiological and technological change (a quarter). CONCLUSION:
      The main determinants of health care use in the Netherlands were old age and
      disabling conditions. Due to ageing and other influences, real health care costs
      in the years to come will increase by an average annual rate of 2.4%.

PMID- 9763843
TI  - [Increase of surgical day treatment in the Netherlands].
AB  - OBJECTIVE: To assess the quantitative development of day surgery in the
      Netherlands. DESIGN: Descriptive. SETTING: St. Antonius Hospital, Nieuwegein, the
      Netherlands. METHOD: Numbers of admissions in the period 1984-1995 were obtained
      from Dutch data bases of the National Hospital Institution (NZi). From SIG Health
      Care Information numbers were obtained with regard to seven specified
      interventions in the years 1991 to 1995, i.e. breast tumour excision, inguinal
      hernia repair, varicose vein operation, laparoscopic sterilisation, knee
      arthroscopy, cataract operation and tonsillectomy. The increase if any of the
      number of interventions in day care was determined by placing the hospitals in
      the order of decreasing proportions of day care, and subsequently applying the
      proportions of the 5th and 10th hospitals, respectively, to the whole group.
      RESULTS: The number of day care admissions rose from 172,000 (9.9% of all
      admissions) to 649,000 (29.1%). Of all interventions studied, the percentage
      carried out in day care increased; the percentages varied greatly from one
      hospital to another. In 1995, the mean number of interventions in daytime was
      115,000 (57% of all 201,000 interventions). The shift from interventions during
      hospitalization to day care would be 42,000 and 51,000 (21% and 25% respectively,
      of 201,000), respectively; operations performed in day care would then amount to
      166,000 (83% of the total number of interventions) and 157,000 (78%). CONCLUSION:
      Of the interventions studied, the proportion carried out in day care increased to
      57%. In view of the intra- and interhospital differences, a considerable increase
      of day care in the near future is possible.

PMID- 9763844
TI  - [Ocular infection by Pseudomonas aeruginosa in a mechanically ventilated
      patient].
AB  - A 59-year-old man developed bilateral keratitis several weeks after the
      initiation of mechanical ventilation because of respiratory failure and sepsis
      following abdominal surgery. Colonisation of the upper airways by P. aeruginosa
      had been established before. Invasion through corneal epithelial defects based on
      dehydration keratitis was the presumed route of infection. Despite aggressive
      treatment, including antibiotics, the infection was rapidly progressive in both
      eyes. The patient died of deterioration of his general condition. In order to
      prevent such eye infections in a patient on mechanical ventilation, there is a
      need of good eye care, prevention of corneal lesions and alertness, especially
      when the patient is colonised by virulent micro-organisms like P. aeruginosa.

PMID- 9763845
TI  - [Major psychiatric side effects of interferon alpha-2b].
AB  - The Netherlands Pharmacovigilance Foundation Lareb and the Drug Safety Unit of
      the Inspectorate for Health Care in 1997 received 6 reports of serious
      psychiatric symptoms during the use of interferon alpha-2b. Of these patients,
      three men aged 42, 49 and 62 years and three women aged 31, 40 and 33 years, two
      had had psychic symptoms before. Depression or psychosis developed 12-24 weeks
      after the start of the use of interferon alpha-2b with 3-10 million IU per week
      subcutaneously because of chronic hepatitis B or C. After cessation of the
      medication, four patients recovered after a few days or weeks; the course of one
      patient was unknown, one patient had committed suicide. Knowledge of these
      psychiatric adverse drug reactions to interferon alpha-2b can contribute to early
      recognition by the physician and timely treatment of the symptoms.

PMID- 9763846
TI  - [More openness about the registration of drugs in the Netherlands. College for
      the Review of Medicinal Products].
AB  - The applications submitted to the Drugs Evaluation Board contain information that
      is important for correct use of the drug in question in clinical practice. Not
      all this information is given in the published literature, certainly not at the
      time of registration. Recently, legal provisions on publication of data in
      connection with a registration were clarified. The Board no longer sees any
      objection to introduction of a national, public assessment report explaining the
      arguments involved. The quality of evaluation of pharmaceutical products, also in
      connection with the reimbursement system, cannot but improve if a justification
      of the evaluation is published.

PMID- 9763847
TI  - [Two cold bones].

PMID- 9763848
TI  - [A hundred years of orthopedics in the Netherlands. X. Sports injuries].

PMID- 9763849
TI  - [The Montignac methods: scientific foundation questionable].

PMID- 9763850
TI  - [Envisioning the future in public health 1997. II. Developments in the state of
      health].

PMID- 9763851
TI  - [Infection with Mycobacterium genavense in 2 HIV-seropositive patients in
      Amsterdam].

PMID- 9763852
TI  - [Netherlands Society of Urology].

PMID- 9763853
TI  - [Hyperthyroidism induced by iodinated roentgen contrast media].
AB  - Three patients with subclinical hyperthyroid goitre, women aged 63, 72 and 75
      years following intravenous administration of an iodinated contrast medium
      developed hyperthyroidism with a marked rise of the concentration of free T4.
      Thyreostatic agents were unsuccessful in two patients, the third was left
      untreated. Hyperthyroidism improved spontaneously in all three. Iodine-induced
      hyperthyroidism is rare and is usually encountered in patients with a pre
      existent autonomous thyroid function. Treatment of iodine-induced hyperthyroidism
      is essentially exclusively symptomatic. Prophylaxis with sodium perchlorate
      should be considered in cardiac patients with a goitre and a subnormal level of
      thyroid-stimulating hormone (TSH).

PMID- 9763854
TI  - [Chronicle of a defective heart valve prosthesis].
AB  - The Bjork-Shiley convexo-concave (BScc) strut fracture problem is about to enter
      its third decade. At present, valve carriers still face the risk of outlet strut
      fracture; a risk which does not seem to decline. The temporising attitude of the
      manufacturer has led to far more victims than would have been necessary but also
      the Food and Drug Administration, regulatory agencies outside the US and the
      medical community share responsibility for this problem.

PMID- 9763855
TI  - [Lessons from a heart valve prosthesis controversy].
AB  - Two lessons are to be learnt from the Bjork-Shiley heart valve prosthesis
      tragedy. In the first place pharmacoepidemiologic studies are seriously hampered
      by recent privacy legislation. Individual patients carrying such a prosthesis
      cannot be traced and advised as to their health risks any more, because their
      legal autonomy has to be respected. This is clearly not to their advantage. In
      the second place the atmosphere of marketing and litigation and the increasing
      dependency of researchers on money from sources with conflicting interests is not
      conducive to a well-informed and balanced judgement of the epidemiological
      evidence of safety and efficacy of medical treatments.

PMID- 9763856
TI  - [Immunology in the clinical practice. XVI. Paraneoplastic syndromes of the
      nervous system: pathogenesis and diagnosis].
AB  - Paraneoplastic neurological syndromes are believed to result from ectopic
      expression of onconeural antigens by tumours. The resulting immune response is
      not only directed against the tumour but also cross-reacts with the same or
      similar antigens in the nervous system. The immune response generates high titred
      autoantibodies that are associated with specific tumours and neurological
      syndromes. Paraneoplastic autoantibodies help diagnose neurological syndromes and
      help direct the search for an underlying tumour. In paraneoplastic syndromes, the
      course of the tumour is relatively mild. Detection of the autoantibodies might
      lead to early diagnosis and immunomodulation and anti-tumour treatment before
      irreversible neuronal cell loss and deficits set in.

PMID- 9763857
TI  - [Treatment of subglottic laryngitis (pseudocroup): steroids instead of steam].
AB  - Traditionally, steaming with warm moist air was recommended for the treatment of
      subglottic laryngitis (pseudocroup). However, no favourable effect has ever been
      demonstrated. Consequently, steaming is no longer to be advised. Systemic
      corticosteroids, already of proven effectiveness in severe croup, were shown to
      be also effective when administered in a single oral dose in moderately severe
      disease. Besides, in various studies, nebulisation of budesonide (2000
      micrograms) with a jet nebuliser had a good effect on the clinical course of
      croup. However, dose-effect studies are still lacking. A single dose of
      corticosteroids, either systemic or inhaled via a jet nebuliser, should be the
      first line therapy in moderate and severe croup syndrome. In milder cases no
      specific treatment is needed as the disease is self-limiting.

PMID- 9763858
TI  - [Roaming through methodology. III. Randomization at the level of the physicians].
AB  - In some studies randomization at the patient level is not possible; randomization
      at the doctor's level can then be applied. However, statistical analysis at the
      level of the individual patient data can lead to wrong conclusions in such a
      study design. By basing the analysis on the averages per doctor a statistical
      test can be performed which guarantees the correct significance level. The
      correct sample size can be found by means of a correction factor that depends on
      the variation between the doctors. The data of a study with randomization at the
      doctor's level can be analysed in a more sophisticated way by means of so-called
      'mixed models' that take account of possible variation between doctors.

PMID- 9763859
TI  - [Tuberculosis of the larynx].
AB  - Laryngeal tuberculosis was diagnosed in two men, a 73-year-old man Dutch by birth
      and a 40-year-old one Turkish by birth. In the former patient it was probably
      primary tuberculosis, in the latter secondary (he had lung tuberculosis as well).
      The clinical picture was highly suggestive of laryngeal carcinoma in both
      patients. They both recovered with chemotherapy. Laryngeal tuberculosis may mimic
      laryngeal carcinoma. The diagnosis is based on Ziehl-Neelsen staining, culture
      and polymerase chain reaction (PCR) on Mycobacterium tuberculosis. Because
      laryngeal tuberculosis is highly infectious, the patient has to be nursed in
      isolation and people in his or her environment have to be screened. The response
      of laryngeal tuberculosis to chemotherapy is good.

PMID- 9763860
TI  - [Pathogenesis of pre-eclampsia].

PMID- 9763861
TI  - [Urination alarm training also successful with 5-7 year olds suffering from
      enuresis nocturna].

PMID- 9763862
TI  - [Two children with an unusual cause of torticollis: primitive neuro-ectodermal
      tumor and Grisel's syndrome].

PMID- 9763863
TI  - [A swelling in the distal part of the thigh].
AB  - A swelling in the distal thigh may be caused by a tumour of bone or soft tissues,
      an aneurysm or an inflammation. Signs of inflammation may render interpretation
      more difficult. Four males aged 60, 48, 15 and 81 years had had a swelling in the
      popliteal space or above the knee, in some cases with pain. Supplementary
      examinations, especially MRI scanning and arteriography did not always result in
      a diagnosis. The diagnosis could be made, however, during operation: an empyemic
      thrombosed popliteal artery aneurysm, a liposarcoma, pyomyositis and suture
      dehiscence of a plastic prosthesis of the popliteal artery. After treatment,
      consisting of or started during the operation, uneventful recovery occurred.

PMID- 9763864
TI  - [Dietary trans-fatty acids: a risk factor for coronary disease].
AB  - Unsaturated fatty acids with their double bond in trans configuration raise serum
      low-density lipoprotein (LDL) cholesterol and lipoprotein(a) levels, and lower
      high-density lipoprotein (HDL) cholesterol in humans when substituted for cis
      unsaturated fatty acids in the diet. These effects should increase the risk of
      coronary heart disease, which is confirmed by epidemiological studies. Trans
      fatty acids are formed from cis unsaturated fatty acids during hydrogenation of
      vegetable oils in food industries. Until recently, major dietary sources of trans
      fatty acids in the Netherlands were frying fats, shortenings, and margarines,
      which in the past contained up to 50% of trans fatty acids. Nowadays, most
      shortenings and margarines sold in the Netherlands have a low trans fatty acid
      content due to manufacturing changes in the recent past. However, frying fats
      used in fast-food outlets still contain over 30% of trans fatty acids. French
      fries sold in these outlets provide 7-8 g of trans fatty acids per portion.
      Producers of frying fats for fast-food outlets therefore should also reduce the
      trans fatty acid content of their products as much as possible.

PMID- 9763865
TI  - [Ambulatory blood pressure measurement].
AB  - Non-invasive ambulatory blood pressure monitoring (ABPM) is used as an additional
      diagnostic procedure particularly in specialist hypertension care. One
      application is diagnosing white coat hypertension. In general practice there is
      no established place for this diagnostic tool so far. At this time several
      studies are being carried out to investigate the prognostic value of ABPM. There
      are protocols of validation for ABPM monitors; nine of the 45 available up to now
      have been approved by the two most important test protocols. Reference values for
      normotension and hypertension are determined for the general population, but not
      for special groups of patients or for exercise conditions. One of the frequently
      mentioned advantages of ABPM over office blood pressure reading is the higher
      correlation of ABPM with hypertensive organ damage. To a large extent this
      superiority is based on the larger number of blood pressure readings. Repeated
      standardized office measurements reduce this advantage of ABPM.

PMID- 9763866
TI  - [Chemotherapy in metastasized breast carcinoma].
AB  - Metastatic breast cancer is still an incurable disease. Standard hormonal and
      chemotherapeutic treatment modalities yield at the best a survival advantage of 1
      to 2 years. However, palliation is still the second, very important goal of
      treatment for metastatic disease. First-line chemotherapeutic treatment with an
      anthracycline-containing regimen induces a response in about half the patients.
      In second-line treatment docetaxel is an effective agent even in patients failing
      first-line therapy with an anthracycline-containing regimen. There is no
      effective standard third-line chemotherapy scheme.

PMID- 9763867
TI  - [Clinical thinking and decision making in the practice. A patient with fever of
      unknown origin].
AB  - A 75-year-old woman was admitted because of fever of unknown origin (FUO). In the
      year before the current admission she developed myalgias and was treated for
      polymyalgia rheumatica with low-dose prednisone. Her complaints persisted and
      prednisone was discontinued. Five months before the present admission she
      developed fever (37.7-38.9 degrees C), malaise, fatigue and occipital headache.
      Laboratory tests showed an elevated erythrocyte sedimentation rate (98 mm in the
      first hour) and a severe hypochromic, slightly microcytic, anaemia. Although a
      recent temporal artery biopsy was negative, a second biopsy was taken which
      showed giant cell arteritis. The patient was treated with high-dose prednisone
      (60 mg daily) and made a full recovery. It is emphasized that temporal arteritis
      is a common cause of FUO in the elderly.

PMID- 9763868
TI  - [The yield of endoscopic follow-up after removal of adenomatous polyps from the
      colon].
AB  - OBJECTIVE: To determine the results of follow-up endoscopy after resection of
      adenomatous polyps from the colon. DESIGN: Retrospective. SETTING: De Heel
      Hospital, department of Internal Medicine, Zaandam, the Netherlands. PATIENTS AND
      METHOD: The 124 patients, 66 males and 58 females, with a mean age of 53 years
      (range: 23-74), in whom a colonpolyp had been removed endoscopically, who had no
      colonic carcinoma and no positive family history, were registered for follow-up
      after one year and after 3 or 5 years. In 1997, data were collected on the polyps
      found and removed at follow-up. RESULTS: At the original coloscopy, 68 patients
      (55%) had one polyp, 46 (37%) had two to four polyps and 10 (8%) > or = five
      polyps. The localizations of the polyps were: rectum 17%, sigmoid 66%, descending
      colon 12%, transverse colon 3%, ascending colon 1% and caecum 1%. Over one-third
      of the polyps were larger than 1.5 cm. Ninety-eight patients underwent a first
      follow-up endoscopy after an average of 12 months (range: 0.4-57); one or more
      polyps were found and removed in 37 of them (38%). At a second follow-up
      endoscopy after an average of 28 months (range: 5.4-68 months), polyps were again
      found and removed in 26 of the 57 patients (46%). If two or more polyps had been
      removed at an earlier coloscopy, the risk of polyps being found again at the next
      coloscopy was larger (p < 0.001).

PMID- 9763869
TI  - [Psychiatric symptoms in refugees reported to the Psychiatric Center De Vonk].
AB  - OBJECTIVE: To determine traumatic experiences and psychological symptoms in
      refugees reported to the psychiatric centre De Vonk, and the relationship between
      biographical data, experiences of violence and post-traumatic stress symptoms on
      the one hand and the referral or admission policy on the other. DESIGN:
      Descriptive. SETTING: Centre '45, refugee unit De Vonk (department for the
      treatment of traumatized refugees and asylum seekers), Noordwijkerhout, the
      Netherlands. The psychiatric centre De Vonk comprises, apart from an outpatient
      clinic and a daytime clinic, a department created for the clinical treatment of
      refugees with symptoms related to traumatization. METHODS: The main biographical
      and background data were collected. The first interview was routinely preceded by
      the Harvard trauma questionnaire (HTQ) and the Hopkins symptom checklist (HSCL
      25), if necessary with the aid of an interpreter. The HTQ measures experiences of
      violence and post-traumatic stress symptoms; the HSCL-25 comprises an anxiety
      scale and a depression scale. RESULTS: Biographical data were obtained from 232
      patients and questionnaire data from 169 patients. The population was
      heterogeneous as regards region of origin, duration of the stay in the
      Netherlands, education and age. Serious forms of violence were reported, such as
      abuse, torture and war violence, and many symptoms of anxiety and depression were
      mentioned. The scores for posttraumatic stress symptoms exceeded the clinical
      reference values in 82% in the group examined. Of the referred patients, 37% were
      admitted to the clinic. CONCLUSION: In spite of the diversity of language,
      culture and education among the refugees/asylum seekers referred to De Vonk, it
      proved adequately possible in practice to use standardized psychological and
      psychiatric instruments in this group of patients. The symptom level of the
      patients referred was particularly high.

PMID- 9763870
TI  - [An rare cause of vaginal discharge: sarcoma botryoides].
AB  - A general practitioner was consulted by a 15-year-old girl, virgo, suffering from
      foetid vaginal discharge. The girl was seen by a gynaecologist after
      antimicrobial treatment had failed. Further investigations revealed that a
      embryonal rhabdomyosarcoma was present, a sarcoma botryoides. The tumour
      originating from the cervix uteri was resected completely after which
      chemotherapy was started. One year later there were no sequelae or indications of
      metastases. Sarcoma botryoides has a better prognosis than other types of
      rhabdomyosarcoma. The prognosis is also influenced by the site of origin, which
      is favourable for the cervix.

PMID- 9763871
TI  - [Subspecialty blood transfusion medicine].
AB  - The unification of Europe, the related principle of self-sufficiency and the
      prevention of blood banks turning into bureaucratic institutes that lose
      connection with bedside medicine underscores the need for training in transfusion
      medicine and its international organization. In most European countries
      transfusion medicine is now recognized as a specialty in its own right. In the
      Netherlands it was decided to recognize transfusion medicine as subspecialty of
      Internal Medicine. This new initiative led to a training programme of 6 years in
      all, of which the last 18 months are devoted to transfusion medicine exclusively.
      The importance of continuous education and practice in both fields is recognized.

PMID- 9763872
TI  - [Fifty years of the column 'Question and Answer'].
AB  - The section 'Question and answer' in the Nederlands Tijdschrift voor Geneeskunde
      (Dutch Journal of Medicine) has existed for over 50 years. Medical questions of
      readers are published anonymously and answered by an anonymous expert consulted
      by the editorial staff. At first the column grew rather large but in the last few
      decades it shrank to only few publications a year. Due to improvements in
      communication (Internet) and provision of information (electronic databases) it
      appears that the column, as a medium for questions of readers, is becoming
      obsolete.

PMID- 9763873
TI  - [Optimization of the antibiotics policy in the Netherlands. II. SWAB guidelines
      for the antimicrobial therapy of pneumonia treated at home and nosocomial
      pneumonia].

PMID- 9763874
TI  - [Optimization of the antibiotics policy in the Netherlands. I. The Foundation
      Task Force for Antibiotics Policy (SWAB)].

PMID- 9763875
TI  - Prooxidant actions of carotenoids in biologic systems.
AB  - The potential for carotenoids to modulate chronic disease risk is currently under
      investigation, and renewed interest has been placed on achieving a better
      understanding of the mechanisms of action of carotenoids in biologic systems.
      Available data currently show that the antioxidant activity of these compounds
      may shift into prooxidant activity, depending on the redox potential of the
      carotenoid molecules as well as on the biologic environment in which they act.
      The prooxidant potency of these compounds is determined by several factors,
      including oxygen tension, carotenoid concentration, and interactions with other
      antioxidants. Prooxidant activity can induce either beneficial or harmful results
      in biologic systems and influence the development of human chronic diseases.

PMID- 9763876
TI  - Effects of chromium on body composition and weight loss.
AB  - Chromium is an essential nutrient involved in the regulation of carbohydrate and
      lipid metabolism. Normal dietary intake of chromium in humans and farm animals is
      often suboptimal. In addition to its effects on glucose, insulin, and lipid
      metabolism, chromium has been reported to increase lean body mass and decrease
      percentage body fat, which may lead to weight loss in humans. The effects of
      chromium on body composition are controversial but are supported by animal
      studies, which increase their validity. A subject's response to chromium depends
      on his or her chromium status, diet consumed, type and amount of supplemental
      chromium, and study duration. There have been no confirmed negative effects of
      chromium in nutritional studies. Chromium is only a small part of the puzzle in
      the control of weight loss and body composition, and its effects, if present,
      will be small compared with those of exercise and a well-balanced diet.

PMID- 9763877
TI  - Agouti/melanocortin interactions with leptin pathways in obesity.
AB  - The cloning of mouse obesity genes and their human homologues provides unique
      opportunities to identify novel cellular targets for therapeutic intervention.
      The first of these to be cloned, agouti, antagonizes central nervous system
      melanocortin receptor (MCR) binding, resulting in hyperphagia and an
      obesity/hyperinsulinemia syndrome. There appears to be significant cross-talk
      between the agouti and leptin signaling systems. Agouti antagonism of central
      nervous system (CNS) MCR binding inhibits the anorexic effects of leptin, whereas
      agouti up-regulates adipocyte leptin expression, serving to limit the magnitude
      of agouti-induced obesity. The effects of agouti and leptin mutations on obesity,
      however, are independent and additive. Agouti also regulates adipocyte lipid
      metabolism, functioning both to increase the expression and activity of lipogenic
      genes and to inhibit lipolysis. Both of these actions occur via a Ca(2+)
      dependent mechanism, suggesting that modulation of adipocyte Ca2+ transport may
      be a key target for further investigation.

PMID- 9763878
TI  - Diet, lifestyle, and colorectal cancer: is hyperinsulinemia the missing link?
AB  - Several dietary and other lifestyle factors have been implicated in the
      development of colorectal cancer. However, the precise nature and actual
      magnitude of the relationship between individual nutrient intakes and other
      lifestyle factors and colorectal cancer risk are not clear. A unifying hypothesis
      has recently been proposed that explains why obesity, physical inactivity,
      alcohol, and consumption of a typical Western diet increase colorectal cancer
      risk. This hypothesis suggests that these dietary and other lifestyle factors are
      associated with insulin resistance and hyperinsulinemia and that
      hyperinsulinemia, in turn, may stimulate growth of colorectal tumors. Two
      recently published large prospective epidemiologic studies indicate a significant
      increase in colorectal cancer risk in subjects with diabetes mellitus, thereby
      supporting this hypothesis.

PMID- 9763879
TI  - Slow-release iodine in local water supplies reverses iodine deficiency disorders:
      is it worth its salt?
AB  - An alternative approach to supplying iodine to isolated populations through the
      use of slow-release iodine in silicone matrices that float in the water supply
      was tested in remote desert areas of the Sudan. There was a differential impact,
      as judged by indicators of iodine nutriture, and these indicators provided
      varying indications of the iodine status of the population.

PMID- 9763880
TI  - Underexploited African grain crops: a nutritional resource.
AB  - The African grain deficit is projected to surpass its current production of 50 x
      10(6) metric tons/year by the turn of the century. The biodiversity of the
      African continent, on which there are more native cereals than on any other
      continent, can serve to reduce the vulnerability of the continent's populations
      at serious risk of food shortages. Traditional grain and root crops have provided
      the energy underpinning for Africa since the emergence of bipedal hominids. By
      resurrecting some of these "lost crops" in their native areas, the food security
      of those areas can be enhanced. In addition, some of these crops lend themselves
      to introduction into other nutritionally challenged areas of the world with
      similar geoclimatic characteristics.

PMID- 9763881
TI  - Acute effects of soft drink intake on calcium and phosphate metabolism in
      immature and adult rats.
AB  - OBJECTIVE: To test the acute effects of the intake of a phosphoric acid
      containing soft drink on acid-base balance and on calcium and phosphate
      metabolism. MATERIAL AND METHODS: We studied 14 young adult male Sprague-Dawley
      rats aged 90 days, and 14 immature animals aged 30 days. Half of the animals in
      each group were randomly assigned to receive either tap water (controls), or Coca
      Cola ad libitum for seven days. After this period, the rats were individually
      placed in metabolic cages to collect 24 hours urine, and they were exsanguinated
      by aortic puncture. Immediately, pH and ionized calcium were measured in whole
      blood. Creatinine, phosphate and total calcium were determined in the urine and
      plasma. Plasma levels of PTH, 1 alpha, 25 (OH)2 D3 and 25 OH D3 were measured by
      IRMA and RIA commercial kits. RESULTS: The animals receiving the soft drink, both
      adults and immature, developed significant hypercalciuria and hyperphosphaturia.
      In immature animals, the plasma pH dropped from 7.45 +/- 0.04 to 7.33 +/- 0.02 (p
      < 0.05) but did not change in adult animals. Ionized calcium dropped
      significantly from 1.06 +/- 0.04 to 0.80 +/- 0.06 meq/L (p < 0.05) in immature
      animals but not in the adult animals. Only immature rats developed significant
      reduction of 1 alpha, 25 (OH)2 D3 and 25 OH D3, whereas only the adult rats
      developed significant hyperparathyroidism. Immature animals showed more severe
      derangement of calcium and phosphate metabolism related to soft drink intake.

PMID- 9763882
TI  - Hemodynamic indexes in newborns using the arteriovenous oxygen content
      difference.
AB  - OBJECTIVE: To determine in peripheral blood samples of newborns (NB) cardiac
      output (Q), cardiac index (CI), systemic vascular resistance index (SVRI), and
      effective oxygen transport (EO2T), through arteriovenous oxygen content
      difference ([C(a-v) O2]). DESIGN: Comparative survey. SETTING: Healthy NBs and
      NBs in intermediate care in third level medical attention units. MATERIAL AND
      METHODS: Forty-seven NB (17 pre-term) were prospectively studied in August and
      September/1995. A blood sample of 0.4 mL was taken from the umbilical or femoral
      vein and from the umbilical, radial or femoral artery. The inferencial statistics
      were done with a t test and Pearson's correlation coefficient. Significance was
      considered if p < 0.05. RESULTS: Cardiac output ranged from 0.3 to 1.4, mean =
      0.6 L/min +/- 0.24 (+/- SD); CI ranged from 1.8 to 6.4 L/min/m2 body surface area
      (mean = 3.3 +/- 1.2); SVRI ranged from 533 to 2,391 dyne/sec/cm-5/m2 BSA (mean =
      1,317 +/- 494); EO2T ranged from 307 to 1,017 mL/min/m2 BSA (mean = 549 +/- 186);
      the [C(a-v) O2] ranged from 3.1 to 10.7% in volume (mean = 6.8 +/- 2.1). No
      significant differences were found in Q between pre-term and full-term NB nor was
      there any correlation between Q and gestational age. CONCLUSIONS: The [C (a-v)O2]
      is a good alternative to obtain indexes in peripheral blood of NB without
      cardiopathy, whenever other less invasive and more sophisticated methods are
      unavailable. In order to calculate the indexes in critically-ill patients, it is
      necessary to measure O2 consumption prior to applying this method.

PMID- 9763883
TI  - [Neuropsychological evaluation in patients with Parkinson's disease].
AB  - OBJECTIVE: To analyze the neuro-psychological performance of patients with
      Parkinson's, disease (PD), in comparison with a group of patients with frontal
      lobe lesions (FLL) and a control group. METHODS: Eighteen patients with PD, 10
      patients with FLL and 10 controlls of similar age and scolarity were studied.
      Neuro-psychological evaluation included tests of the visuospatial, execution,
      attention and concentration, memory and language areas. The tests were classified
      in two categories: those requiring motor responses and those that do not.
      RESULTS: Patients with PD and FLL had lower scores them the controls in the
      visuospatial, attention and concentration and language areas, with statistical
      significance in some cases. The differences with the controls persisted in some
      tests requiring and not requiring motor response. CONCLUSIONS: Frontal lobes have
      an important role in the neuro-psychological profile of patients with PD.
      Cognitive deficits in these patients is unrelated to the motor impairment of the
      disease.

PMID- 9763884
TI  - [Sonographic patterns by transcranial Doppler in acute cerebral infarction].
AB  - AIM: To evaluate the correlations between the patterns of Transcranial Doppler
      (TCD) and the extent and pathophysiologic mechanism of the ischemia as well as
      the prognosis of patients with acute ischemic stroke. METHODS: 37 patients with
      ischemic stroke within the first 24 hours of evolution were examined using TCD,
      neuroimaging, and neurologic state at admission and disarcharge. The TCDs were
      grouped into four categories: normal, stenotic, hemispheric asymmetry and trunk
      occlusion of the middle cerebral artery (MCA); they were correlated with the
      extent of brain damage, pathophysiologic mechanism of the stroke and prognosis.
      RESULTS: Normal TCD was highly predictive of lacunar infarction secondary to
      small vassels disease (p = 0.01) and good recovery (p < 0.02). The stenotic and
      hemispheric asymmetry patterns correlated highly with a cortical infarctions (p <
      0.05) and a cardioembolic mechanism. The occlusion of the MCA was highly
      correlated with a large infarction (p < 0.01) and with poor outcome and death (p
      = 0.004). CONCLUSIONS: Our data show that TCD has a value in predicting the
      prognosis and the severity, location and pathophysiologic mechanism of cerebral
      strokes.

PMID- 9763885
TI  - [Clinical competence and clinical performance in diabetes].
AB  - OBJECTIVE: To evaluate at the primary health care level, clinical competence and
      clinical performance of physicians in the diagnosis and management of diabetes
      mellitus type II. MATERIAL AND METHODS: Physicians in 4 primary medical care
      units were evaluated using two instruments: a multiple choice questionnaire
      (true/false/don't know type) with 224 questions about diabetic cases to explore
      clinical competence, and a second one on management of cases of diabetes to
      explore the performance in two patients. Both instruments were validated by
      experts. The instruments were applied simultaneously to 59 physicians in two
      units and only the competence instrument to another 59 physicians of the other
      two units. RESULTS: There was a low clinical competence in 57% of the physicians
      and without differences between the four units. In performance there was a
      significant differences in favor of the unit with less work load; 56% of the
      physicians had a very poor performance level. A Spearman correlation competence
      versus performance was low in both units (0.16 and 0.10). CONCLUSIONS: The
      majority of the physicians had poor or very poor competence and performance and
      the latter increased under unfavourable working conditions. There was a
      qualitative difference between our instruments as they were not correlated. It is
      necessary to improve the working conditions in these units to stimulate their
      physicians.

PMID- 9763886
TI  - [Parinaud's syndrome in children].
AB  - OBJECTIVE: To describe the clinical and ethiologic findings of children with
      Parinaud's syndrome. MATERIAL AND METHODS: 11 children fulfilling the clinical
      criteria for Parinaud's syndrome were studied. The mean age was 10 years with a
      range of 10 months to 14 years. RESULTS: Seven cases were tumors (pineal
      germinoma in four and one each with teratoma, astrocytoma, and an undefined
      tumor); the remaining 4 cases corresponded to arachnoid cyst in the III
      ventricule, cysticercosis, tuberculoma and multiple sclerosis. The main treatment
      was surgical including ventriculoperitoneal shunt because of hydrocephalous
      secondary to mechanical obstruction. Chemotherapy and radiotherapy were also used
      for the tumor cases, and steroids for the multiple sclerosis patient.
      CONCLUSIONS: In contrast to adults, Parinaud's syndrome in our children was
      associated with a mass, mainly tumoral, which interrupted the afferent and
      efferent connections of the midbrain structures, such as posterior commissure,
      riMLF or the interstitial nucleus of Cajal.

PMID- 9763887
TI  - The role of commercial plasmapheresis banks on the AIDS epidemic in Mexico.
AB  - OBJECTIVE: To characterize the circumstances underlying the epidemic of AIDS
      associated with blood transfusion in Mexico and to explore the possible
      mechanisms for its dissemination. METHODS: A retrospective analysis comparing the
      total number of AIDS cases and transfusion-associated AIDS cases and the
      male:female ratio reported in Mexico and the U.S. from 1981 to 1996 was done. We
      analyzed the relationship between the location of plasmapheresis banks and the
      geographic distribution of transfusion-associated AIDS cases and AIDS cases among
      paid donors in order to assess the possible role of plasmapheresis banks in its
      dissemination. RESULTS: The proportion of transfusion-associated AIDS in the
      total number of cases was significantly higher in Mexico than in the U.S. from
      1987 through 1996 (p < .0001). A rapid drop in the male:female ratio of AIDS was
      observed in Mexico but not in the U.S. coinciding with a growing number of
      transfusion associated cases; transfusion has been the main risk factor for AIDS
      in women in our country. In 1986, seven States and Mexico City had plasmapheresis
      banks: they reported 90% of the cases associated to paid donation and 75% of
      those associated to transfusion, despite the fact that commercial blood banks
      without plasmapheresis facilities existed in 23 of the other 24 States.
      CONCLUSION: There was a difference on the frequency of transfusion associated
      AIDS between Mexico and the U.S. which reached epidemic proportions in Mexico. We
      believe that plasmapheresis banks played a major role in the dissemination of the
      infection in Mexico as paid donors provided a third of the blood used in Mexico
      in 1986. These findings highlight important implications for the prevention of
      AIDS in developing countries where commercial plasmapheresis practices are still
      in operation.

PMID- 9763888
TI  - [Diabetes and pregnancy in Mexico].
AB  - OBJECTIVE: To review the Mexican studies published in the last 15 years on
      diabetes mellitus (DM) and pregnancy. MATERIAL AND METHODS: We found five
      descriptive studies on DM and pregnancy and six on the detection of gestational
      diabetes (GDM) in normal pregnant women using the oral glucose tolerance test
      (OGTT). RESULTS: The first group of studies comprised 689 patients: 331 with
      pregestational DM type 2 and 32 type 1; the other 326 patients (47%) had GDM
      established by clinical symptoms and hyperglycemia, or by fasting hyperglycemia
      (> 140 mg/dL) in at least two ocassions. The distribution of types 1 and 2 was
      similar in the five studies. Maternal complications were toxemia in 18%,
      polyhydramnios is 10% and urinary infection in 6%. Perinatal mortality was 7%,
      congenital malformations in 6%, macrosomia in 25% and prematurity in 8%. In the
      puerperium 71 women with GDM were reevaluated: 48 (68%) were type 2, one (1%)
      type 1, three (4%) glucose intolerance (GI) and 19 (27%) were normal to an OGTT
      test. The six studies on GMD in normal pregnants were done using the OGTT. Three
      studies were done in the city of Monterrey, state of Nuevo Leon and show a
      prevalence of 4.3 to 6%, mean 5.3%. The other three studies show a prevalence of
      10.5 to 11%. In the puerperium, 26 women were reevaluated: only three were type 2
      (12%), five GI (19%) and 18 (69%) had a normal response to the OGTT. CONCLUSIONS:
      Type 2 DM is the more frequent type of diabetes associated to pregnancy in
      Mexican groups; the systematic screening for GDM in normal pregnant women yields
      4 to 11% of positivity.

PMID- 9763889
TI  - [Quality control of 135 histopathological reports of colo-rectal carcinoma].
AB  - OBJECTIVE: To evaluate the information content in our surgical pathology reports
      of colon and rectum carcinoma. SETTING: A third level hospital. DESIGN:
      Consecutive surgical reports from 1988 to 1994 were retrieved. The gross and
      histological variables with prognostic relevance according to the TNM system were
      registered using a checklist with standardized variables as proposed by two
      groups of pathologists. The adequacy of our reports was surveyed counting the
      number of histopathological variables in relation to the 11 prognostic parameters
      that must be included in routine surgical reports of large colon carcinomas.
      RESULTS: The surgical reports were 135. The histologic type, tumor grade and
      histological tumor invasion were provided in most of the reports. In 90% the
      lymph node characteristics were described and 85% had gross and histologic margin
      assessment. But other variables were poorly informed, i.e. vascular invasion was
      informed in one case (0.7%). CONCLUSIONS: Our surgical reports were considered
      adequate as 113/135 (84%) recorded more than eight prognostic variables.
      Insufficient data were: 1) a poor gross description; 2) lack of tumor grading in
      12%; and 3) omission of anatomic site in 29%.

PMID- 9763890
TI  - [Four cases of parathyroid cancer].
AB  - Parathyroid carcinoma is a rare cause of primary hyperparathyroidism with a
      prevalence ranging between 0.5 and 4%. Because of their aggressiveness, prompt
      diagnosis and treatment are mandatory. A parathyroid carcinoma was found in four
      patients (4.5%) of 88 patients who underwent surgical cervical exploration for
      primary hyperparathyroidism at the Institute Nacional de la Nutricion in a period
      of seven years. Our paper gives the clinical characteristics, diagnosis,
      treatment and outcome of the four patients.

PMID- 9763891
TI  - [Giant acinic cell parotid gland adenocarcinoma of the papillary- cystic type].
AB  - A case of a 38-year-old male having an acinic cell adenocarcinoma of the parotid
      gland is reported. The tumor measured 22 cm and histologically it was of the
      papillary-cystic type. The following features were of interest: 1) the tumor size
      surpassed the size of previous reported acinic cell adenocarcinomas by 9 cm; and
      2) the rarity of its histological variety (cystic papillary) demanded
      immunohistochemical and electron microscopic studies to confirm the diagnosis.

PMID- 9763892
TI  - [A case of Hallervorden-Spatz disease with magnetic resonance imaging data].
AB  - Hallervorden-Spatz disease (HSD) is an uncommon disorder, progressive and
      degenerative of the basal ganglia. It begins in the first or second decade of
      life and is characterized by a dominant extrapiramidal signs, dystonia and
      progressive dementia. It is autosomic recessive, although sporadic cases are seen
      in 15%. There is no biological marker for the disease. The post-mortem findings
      include iron deposits in the globus pallidum and pars reticulata of the
      substantia nigra. Magnetic resonance imaging (MRI) in T2 shows symmetric
      hypointense lesions in both globus pallidum with a hyperintense center: giving
      the "tiger's eye" sign. This is the first case reported in Mexico of sporadic HSD
      with typical clinical and MRI findings.

PMID- 9763893
TI  - [Leiomyosarcoma associated with Epstein-Barr virus in an adult with renal
      transplant].
AB  - Recently the association between the Epstein-Barr virus (EBV) and smooth muscle
      lesions has been described in immunosuppressed children but it is infrequent in
      adults. The role of EBV in the pathogenesis of these lesions is obscure. We
      presents a 28 year old man with end stage renal disease transplanted in 1994. Two
      years later he developed several nodular lesions that affected both lungs, liver,
      spleen, retroperitoneal ganglia and the left thigh; one year later he died. The
      surgical specimen from the thigh and a liver biopsy were diagnosed as
      leiomyosarcoma. Immunohistochemical reactions against vimentin and smooth muscle
      actin were positive. In situ hybridization disclosed positivity against EBV
      nuclear antigens (EBNA-2) in neoplasic cells. This is the first case of sarcoma
      in transplanted patients of our institution and represents a rare case of
      leiomyosarcoma associated with EBV in adults.

PMID- 9763894
TI  - A case of pleomorphic lipoma of the hypopharynx.
AB  - We report the first case of pleomorphic lipoma in the hypopharynx. A 69-year-old
      man was admitted because of a 12 year history of dysphagia and cough. Direct
      laryngo-pharyngoscopy revealed a polypoid, yellow, smooth, submucosal tumor with
      well defined borders. At CT scan the tumor showed a hypodense pattern and
      measured 3 cm. Microscopically the neoplasm was composed mainly by typical
      lipomatous tissue, bundles of collagen and pleomorphic multinucleated cells, some
      with floret-like appearance. Lipoblasts and mitoses were not found. Six months
      after resection there was no evidence of recurrence.

PMID- 9763895
TI  - [New concepts on the physiopathology, diagnosis, and treatment of achalasia].
AB  - OBJECTIVES: To review the most relevant publications on the pathophysiology,
      clinical manifestations, diagnosis and treatment of esophageal achalasia, and the
      clinical experience achieved at our institution in order to propose a practical
      strategy to facilitate the management of these patients. DATA SOURCES: Manual and
      MEDLINE search of key articles published between January 1986 and July 1997 in
      addition to publications of our institute of thirty years. STUDY SELECTION: All
      kinds of publications with substantial clinical experience, new information or
      research protocols. DATA SYNTHESIS: Achalasia is an uncommon disorder of the
      myenteric plexus of the esophagus. Main symptoms are dysphagia, regurgitations
      and chest pain. The diagnosis is established by manometric criteria.
      Esophagogram, endoscopy and radionuclide esophageal emptying test help to
      differentiate other conditions and evaluate the response to treatment.
      Pharmacotherapy may provide relief to patients with mild symptoms and is useful
      for patients with high risk of complications. Dilations and myotomy are safe,
      effective and long lasting procedures. Botulinum toxin may be effective in
      selected cases. Predictive factors of response have been described for each
      therapy. CONCLUSION: A systematic approach to the management of patients with
      achalasia is necessary. Introduction of new therapies as botulinum toxin and
      minimal invasion surgery are changing the therapeutic decisions in this field.
      Drugs and BoTox are considered the first line of treatment for high risk patients
      and dilation and surgery for patients with no risk.

PMID- 9763896
TI  - Gene transfer into hematopoietic cells: progress, problems and prospects.
AB  - Gene therapy is the introduction of genetic material into somatic cells in order
      to correct a genetic defect or provide a new therapeutic function. Among the
      numerous potential cellular targets for gene therapy, hematopoietic stem cells
      (HSC) may be viewed as one of the best candidates for such genetic modification.
      More than 250 clinical gene transfer protocols have been reported from around the
      world, and almost one in three involves manipulation of hematopoietic cells. The
      introduction of a new gene into the DNA of HSC and expression of the gene product
      in their progeny are exciting approaches to treatment of congenital and acquired
      diseases. Although it has been shown that hematopoietic progenitor cells, or even
      LTC-IC, can be easily transduced with high efficiency by retroviral vectors in
      vitro, and that long-term expression and high transduction can be obtained in
      mice after transplantation of the gene manipulated cells, this has not been
      observed in primate models or in human clinical trials. The reason for this
      discrepancy is not properly known. The major problems of gene therapy for cancer
      have been transduction rate, selectivity, and effectiveness due to the
      heterogeneity of genetic alterations found in human tumors. Overcoming these
      limitations in gene therapy requires not only improvement in cell biology and
      immunology, but also development of better delivery systems. Nevertheless, gene
      therapy is still promising and offers encouragement for future applications in
      clinical practice.

PMID- 9763897
TI  - Echocardiographic assessment of left and right ventricular diastolic functions in
      children with dilated cardiomyopathy.
AB  - We evaluated left and right ventricular diastolic functions by pulsed Doppler
      echocardiography in 16 children with dilated cardiomyopathy and in 20 healthy age
      matched control subjects. The cardiomyopathy group demonstrated an abnormal
      relaxation pattern of the left ventricle. In the cardiomyopathy group compared to
      normal subjects, peak early filling velocities (43.3 +/- 11 cm/s versus 60.4 +/-
      11 cms/s, p < 0.01), the corresponding velocity-time integrals (3.3 +/- 1.4 cm
      versus 4.6 +/- 1.2 cm, p < 0.01) and the ratio of peak early filling velocity to
      late filling velocity (1.22 +/- 0.47 versus 1.49 +/- 0.23, p < 0.05) were
      significantly lower whereas isovolumic relaxation time was significantly longer
      (58.9 +/- 19.8 ms versus 49.7 +/- 8.9 ms, p < 0.05). In addition, right
      ventricular diastolic filling was also impaired in children with dilated
      cardiomyopathy. Peak early filling velocities (41 +/- 7.9 cm/s versus 47.5 +/-
      8.8 cm/s, p < 0.05) and the corresponding velocity time integrals (3.0 +/- 1.0 cm
      versus 3.87 +/- 1.1 cm, p < 0.05) were significantly decreased, while isovolumic
      relaxation time was significantly increased (60.6 +/- 16.3 ms versus 52.2 +/-
      12.8 ms, p < 0.05) in the cardiomyopathy group. The study suggests that
      abnormalities of both right and left ventricular diastolic function may occur,
      and should be searched for, in pediatric patients with dilated cardiomyopathy.

PMID- 9763898
TI  - DNA diagnostic tests in Xp21 dystrophy families for prenatal diagnosis.
AB  - Duchenne and Becker muscular dystrophies are X-linked genetic disorders
      characterized by dystrophin gene defects. We have studied 250 families with
      Duchenne and Becker muscular dystrophies (D/BMD) by molecular genetic methods
      since 1992. Nineteen exons of the dystrophin gene were analyzed for deletion. In
      families with no deletion, linkage analysis was performed to follow the
      inheritance of mutant alleles in the affected families. Twenty of these families
      requested prenatal diagnosis. Six mothers were found to be non-carriers (99%
      accuracy), thus fetuses were examined in the remaining 14. Two fetuses were
      affected and terminated. We report our experience and our current clinical
      practice in providing prenatal studies for D/BMD.

PMID- 9763899
TI  - Pro-inflammatory cytokines, lymphocyte subsets and intravenous immunoglobulin
      therapy in Guillain-Barre syndrome.
AB  - Both cell-mediated immunity and humoral factors are involved in the pathogenesis
      of Guillain-Barre syndrome (GBS). Intravenous immunoglobulin (IVIG) has been
      reported to be a practical, effective and safe treatment in childhood GBS,
      although the mode of action of IVIG remains uncertain. We studied pro
      inflammatory cytokines (interleukin-2, interleukin-1 alpha and tumor necrosis
      factor-alpha) in plasma and cerebrospinal fluid (CSF) and lymphocyte subsets in
      peripheral blood both in the acute phase and in the recovery period in six
      children with GBS treated with IVIG. Flow cytometry was used to determine the
      subsets of lymphocytes in peripheral blood, and cytokines analyses were performed
      by using ELISA technique. Results were compared with a control group of 20
      healthy children. A standard protocol of IVIG (400 mg/kg/day for 5 days) was
      administered to all the patients. Plasma interleukin-2 concentrations and the
      number of HLA DR+ active T cells in peripheral blood were significantly higher in
      the acute phase of the disease than in the recovery period and in healthy
      controls. There was no significant difference in the other cytokine
      concentrations in plasma and CSF or in the other lymphocyte subsets in peripheral
      blood. Our data indicate that IVIG may provide its possible therapeutic effect by
      acting in the cell-mediated immunity in GBS patients.

PMID- 9763900
TI  - Long-term follow-up of hepatitis B virus carriers with normal transaminases
      levels.
AB  - There has been very little data recorded on the natural course of chronic
      hepatitis B virus infection in asymptomatic children. In order to assess the
      natural course of liver disease in hepatitis B surface antigen (HBsAg) carriers
      with normal liver tests, 124 such children (81 males, 65.3%) were followed for
      six to 144 months (mean 36.8 +/- 22.8 months). Liver tests and hepatitis B virus
      (HBV) markers were tested at least every six months. In the beginning, hepatitis
      B e antigen (HBeAg) was positive in 61 (53%) of the 115 carriers of HBsAg who
      were tested. Anti-HBe was positive in 51 (44.3%), and both HBeAg antigen and anti
      HBe were negative in three (2.7%) carriers. The prevalence of HBeAg was not
      affected by the patient's age or sex. During follow-up, 11 patients (18%) lost
      HBeAg (a mean annual clearance rate of 5.8%), and 12 patients (9.7%) lost HBsAg
      (a mean annual clearance rate of 3.1%). We found no difference in the clearance
      of HBsAg and HBeAg by age and sex. The presence of another HBsAg positive person
      in the family affected HBsAg clearance rate but not HBeAg clearance. Only seven
      patients (5 HBeAg positive and 2 anti-HBe positive) developed transient
      elevations in liver transaminases. Three of five HBeAg positive children cleared
      HBeAg after transaminases elevations. Of the five patients who underwent
      percutaneous liver biopsies, non-specific changes were found. It is concluded
      that hepatitis B carriers with normal liver tests should be followed with liver
      function tests alone and that long-term prognosis is good.

PMID- 9763901
TI  - Detection of early anthracycline-induced cardiotoxicity in childhood cancer with
      dobutamine stress echocardiography.
AB  - Asymptomatic long-term survivors of childhood cancer treated with anthracyclines
      may have latent cardiac dysfunction which is undetected by commonly used
      echocardiographic methods. A more sensitive echocardiographic screening test,
      dobutamine stress echocardiography, was performed on 22 patients (mean age 9.10
      +/- 3.79 years) treated with 75 to 450 mg/m2 of anthracyclines (mean 210.45 +/-
      127.34) and results were compared with 22 healthy age-matched control subjects.
      Echocardiographic Doppler studies were performed after each dobutamine infusion
      of 0.5, 2.5, 5 and 10 micrograms/kg/min. Although left ventricular mass was
      decreased and end-systolic walls stress increased in the patient group when
      compared with the control subjects (p < 0.01 and p < 0.05, respectively), no
      differences were found between shortening fraction and ejection force in control
      subjects and patients, at rest and during each dobutamine infusion. A decreased
      mitral E/A ratio (ratio of early-to-late peak filling velocity) was demonstrated
      in anthracycline-treated patients only during dobutamine infusion (p < 0.01). Our
      data showed left ventricular diastolic dysfunction during intropic stimulation
      with dobutamine, and suggest that dobutamine stress echocardiography is a useful
      technique for evaluating the cardiac status of anthracycline-treated patients on
      a long-term basis.

PMID- 9763902
TI  - Magnetic resonance imaging (MRI) findings in isolated growth hormone deficiency.
AB  - In this study the presence of pituitary-hypothalamic abnormalities was searched
      by magnetic resonance (MR) imaging in 30 children (18 males and 12 females, aged
      7.4 to 23 years) with isolated growth hormone deficiency (IGHD). Small anterior
      pituitary was demonstrated in 18 patients and ectopic posterior pituitary (EPP)
      in four of them. Pituitary stalk was found to be thin in two patients with
      anterior pituitary hypophasia and EPP and was visible only in post-gadolinium
      images. In one patient, a hypothalamic mass was found and the bright spot of the
      posterior pituitary was found without diabetes insipidus, possibly due to a
      variation in the intensity of the bright signal. Eight patients had normal
      pituitary imaging suggesting functional damage. In all five patients with
      familial growth hormone deficiency the anterior pituitary was hypoplastic. We
      conclude that a high percentage of patients with IGHD had anomalies of the
      hypothalamo-pituitary region, which could be demonstrated by MR imaging.
      Furthermore, the low frequency of perinatal abnormalities in these patients
      suggested developmental defect as the cause of the morphostructural
      abnormalities. The presence of the familial cases with the same defect pointed to
      the genetic origin in some instances.

PMID- 9763903
TI  - Plaque radiotherapy in the management of retinoblastoma.
AB  - Retinoblastoma is the most common intraocular malignant tumor in childhood and is
      radiosensitive. We treated five patients with solitary intraocular retinoblastoma
      using iodine-125 plaque radiotherapy as a primary procedure. Tumor basal
      diameters ranged from six to 16 mm and thickness ranged from three to 11 mm. The
      radiation dose delivered to tumor apex ranged from 3500 to 5000 centigrays. All
      tumors regressed considerably within a follow-up ranging between seven to 12
      months. There was no tumor recurrence or any complications related to plaque
      brachytherapy within this early period. We concluded that plaque radiotherapy is
      an effective method in local tumor control and allows eye preservation in
      patients with retinoblastoma.

PMID- 9763904
TI  - Urinary calcium excretion of children living in the east region of Turkey.
AB  - We screened 1647 randomly selected Turkish primary school children to detect the
      prevalence of hypercalciuria. Ninety-seven children had hypercalciuria, with a
      prevalence of 5.88 percent. Mean Uca/Ucr ratio was 0.135 +/- 0.108; mean Uca/Ucr
      value for girls was 0.139 and for boys 0.130 (p > 0.05). Mean Uca/Ucr of boys
      with hypercalciuria was 0.341 +/- 0.09 and of girls 0.327 +/- 0.08 (p > 0.05). Of
      these 97 children all investigations could be completed in only 40 and these
      cases were considered to be idiopathic. Twelve children (21%) had a family
      history of consanguinity and 17 (29.8%) of renal stones. The relation between
      blood parathormone and Uca/Ucr ratio was not statistically important (p > 0.05).

PMID- 9763905
TI  - Peroneal nerve injuries as a complication of injection.
AB  - Ten children (8 males, 2 females) diagnosed with peroneal nerve injury as a
      complication of injection were included in this study. The age of the children
      ranged between four to seven years (mean 6.5 +/- 1.25 years). Physiotherapy and
      rehabilitation protocol included superficial heat, neuromuscular electrical
      stimulation (either galvanic or faradic current according to the response
      elicited), electromyographic biofeedback, exercises (passive, active-assistive
      and active), and orthotic support. Before treatment, foot-drop and steppage gait
      were observed in all the patients; both were remedied. The post-treatment muscle
      strength and electrodiagnostic test results showed statistically significant
      improvement when compared with pretreatment values (p < 0.05). We believe that
      our relatively favorable results in this study, manifested as shorter recovery
      time with no residual deficits, may be related to early intervention with an
      extensive physiotherapy program.

PMID- 9763906
TI  - The role of PAF and leukotrienes in bioincompatibility of cuprophane membranes in
      hemodialysis.
AB  - Inflammatory lipid mediators, PAF and leukotrienes (LTs), are thought to have an
      important role in biocompatibility in hemodialysis. PAF, LTB4 and LTC4 were
      studied both in controls (n: 12) and in 11 children on regular hemodialysis (150
      minutes) with cuprophane dialyzers. Blood samples were collected initially (0'
      precapillary), at first minute (1'-postcapillary) and at one hour after the
      hemodialysis sessions (210'-venous). Presence of LTs and high levels of PAF in 0'
      samples compared to levels in controls and significant increases in 1' samples
      suggested the alterations in PAF and LTs likely originated from the peripheral
      leukocyte activation. In 210' samples, PAF and LTs levels were decreased but
      still higher than the levels in 0' samples. This study suggested that PAF and
      LTB4 may be the control elements in biocompatibility in hemodialysis with
      cuprophane membranes, and demonstrated that the effects of activation last until
      the following session.

PMID- 9763907
TI  - Intermittent-low dose G-CSF treatment in a patient with chronic neutropenia.
AB  - Chronic neutropenia in childhood has many definable causes and thus a clear cause
      cannot be identified in a large group of patients. Since the committed stem cell
      is involved in this disorder, growth factors such as granulocyte colony
      stimulating factor (G-CSF) may play an important role in the treatment of
      severely affected children. Because of the side effects and cost, the use of G
      CSF should be restricted to a minimum dose. Here we report a child with chronic
      neutropenia in whom intermittent-low doses of G-CSF were successfully used over a
      long period.

PMID- 9763908
TI  - Hydatid cyst mimicking pulmonary hematoma in a patient with hemophilia A.
AB  - We present a patient of 2.5 years of age with hemophilia A and a pulmonary
      hydatid cyst. A chest x-ray taken by chance showed a paracardiac opacity
      resembling an intrapulmonary hematoma which did not reduce in size after
      infusions of fresh frozen plasma and factor VIII but rather enlarged.
      Transabdominal ultrasound, colored echocardiography, thoracic computed tomography
      and magnetic resonance imaging findings were consistent with a cyst that was
      firmly attached on the border of the right atrium and also indented it; the wall
      was remarkably thick with no internal echoes. Hydatid cyst was diagnosed after
      thoracotomy.

PMID- 9763909
TI  - Complete atrioventricular heart block in congenital hypothyroidism.
AB  - Severe hypothyroidism in children is known to produce cardiac abnormalities such
      as asymmetric thickening or hypertrophy of the interventricular septum, smaller
      internal dimensions of the left ventricle, a smaller left ventricular outflow
      tract, and less systolic septal excursion. In this report, we present a 1.5-year
      old boy who was admitted to our hospital because of growth retardation. According
      to the clinical and laboratory findings, congenital hypothyroidism, dilated
      cardiomyopathy (DCMP), atrioventricular complete heart block and secundum type
      atrial septal defect were diagnosed.

PMID- 9763910
TI  - Balloon atrial septostomy under echocardiographic guidance. Case report.
AB  - A seven-days-old male neonate was transferred to our institution in critically
      ill condition. Echocardiographic (ECHO) examination revealed the transposition of
      the great arteries (TGA) with a small ventricular septal defect. In the
      laboratory examination, arterial oxygen saturation was 29 percent and pH was
      7.16. The poor condition of the neonate led us to decide to perform an immediate
      bedside balloon atrial septostomy (BAS) in the intensive care unit (ICU) with
      ECHO guidance. The umbilical vein was cannulated with a 5 Fr. Miller BAS
      catheter. Four balloon passes were performed resulting in large atrial septal
      defect. After the procedure, arterial oxygen saturation was measured at 40
      percent. In TGA, the baby may present with severe hypoxia and may need management
      in the ICU. Emergency BAS may improve the clinical condition of the patient.
      Transferring the baby, who is mechanically ventilated (and is in openbed), to the
      catheterization laboratory takes time and can be harmful for him, and carries
      risk of extubation and heat loss. The limitations of transthoracic ECHO guidance
      of BAS include the possibility of a poor ECHO window in an ill neonate on
      assisted ventilation and possible interference with maneuverability for both
      echocardiographer and catheter operator. It also carries the risk of
      contamination of the sterile field. When the advantages and disadvantages of
      transthoracic ECHO guidance are considered, transferring the baby to the
      catheterization laboratory can cause problems and time loss. Thus, ECHO-guided
      BAS at bedside is an efficient and good alternative. The transumbilical approach
      may be easier in the first few days of life.

PMID- 9763911
TI  - Occult pneumococcal septicemia and pneumococcal pneumonia complicating
      pneumatoceles in a previously healthy child.
AB  - Fulminating pneumococcal septicemia without an obvious focus of infection is very
      rare in previously immunocompetent children older than two years. Furthermore,
      pneumatocele formation in pneumococcal pneumonia is uncommon. The majority of
      pneumatoceles are self-limited and disappear spontaneously. Here, we report a six
      year-old healthy child with occult pneumococcal septicemia and pneumococcal
      pneumonia secondary to septicemia. Giant pneumatoceles causing respiratory
      insufficiency formed secondary to the pneumococcal pneumonia and were aspirated
      via needle under fluoroscopic guidance.

PMID- 9763912
TI  - Congenital sialidosis.
AB  - Congenital sialidosis is a rare disease resulting from the absence of
      neurominidase and presenting with hydrops fetalis, hepatosplenomegaly, dysmorphic
      features, vacuolated lymphocytes and extensive vacuolation of the connective
      tissue. Elevated levels of sialooligosaccharides in the urine is characteristic.
      We describe a newborn baby with congenital sialidosis and discuss the
      difficulties in reaching the diagnosis.

PMID- 9763913
TI  - Cherubism: a radiological and clinical presentation.
AB  - Cherubism is the hereditary form of the fibrous dysplasia of the jaws, but it may
      be seen sporadically as well. The disease has a self-limited nature and is rarely
      apparent before the age of two. There is no need to interfere surgically with
      these lesions of the mandible or the maxilla unless the child is severely
      affected, i.e. the disease deteriorates respiration, deglutition, vision, or the
      psychiatric makeup of the child due to cosmetic reasons. The clinical
      presentation and radiological evaluation of these children are so typical that
      the pediatrician and pediatric otolaryngologist need to be informed about this
      rarely seen disease. A case of a cherubic child, with his clinical appearance as
      well as his radiological evaluation, and discussion about the clinical outcome
      are presented.

PMID- 9763914
TI  - A case of a four-day-old male with Carpenter's syndrome with transposition of
      great arteries.
AB  - Carpenter's syndrome (acrocephalopolysyndactyly type II) is an autosomal
      recessive syndrome characterized by peculiar facies, synbrachydactyly on fingers
      and preaxial polysyndactyly on feet. To our knowledge there are about 40 reported
      cases of Carpenter's syndrome in the literature. Congenital heart disease is an
      uncommon entity in Carpenter's syndrome. In the case we present, transposition of
      great arteries, subpulmonic ventricular septal defect (VSD) and secundum atrial
      septal defect (ASD) were diagnosed with echocardiographic examination. Therefore,
      a cardiologic examination should be done in every newly diagnosed case of
      Carpenter's syndrome for possible heart defect. Early fatality is seen in
      Carpenter's syndrome cases associated with congenital heart disease. This is
      particularly important from the genetic counselling point of view.

PMID- 9763915
TI  - Lupus vulgaris secondary to single BCG vaccination. A case report.
AB  - A 10-year-old girl with lupus vulgaris following single BCG vaccination is
      reported. She had a 15 x 20 cm painless lesion covering her left shoulder,
      axilla, triceps and biceps region. PPD test was positive. Histopathological
      picture was identical to lupus vulgaris.

PMID- 9763916
TI  - [Focus on intensive therapeutic strategy in type 2-diabetes].

PMID- 9763917
TI  - [Leukemia in children].

PMID- 9763918
TI  - [Multidisciplinary diagnostics in acute leukemia].
AB  - Establishing the exact diagnosis of patients suspected for acute leukemia is of
      paramount importance not only for instituting first-line treatment, but also for
      prognosticating the patient and determining the status of disease, e.g. in
      relation to minimal residual disease. In this overview the most recent
      developments regarding the methods for leukaemia diagnosis (cytology, histology,
      immunology, cytogenetics and molecular biology) are described and their
      respective merits and drawbacks are discussed. Special emphasis is given to the
      temporal relationship for application of the methods in the course of disease in
      these patients.

PMID- 9763919
TI  - [Hypertrophic cardiomyopathy].
AB  - Hypertrophic cardiomyopathy is a heterogeneous, progressive disease with a
      variable age of debut. Hypertrophic cardiomyopathy is characterized by myocardial
      hypertrophy with a bizarre fibre disarray. Angina pectoris, dyspnoea and syncope
      are the most frequent symptoms. Hypertrophic cardiomyopathy is an important cause
      of sudden death, especially in children and young adults. The aetiology is
      genetic in more than 60% of the cases, with an autosomal dominant mode of
      inheritance. More than 50 different mutations involving six genes have so far
      been associated with the development of hypertrophic cardiomyopathy. These
      mutations are located to genes coding for several of the proteins in the cardiac
      sarcomere. The protein changes seem to compromise contractility as well as
      sarcomere assembly, thereby secondarily causing compensatory hypertrophy. The
      management of hypertrophic cardiomyopathy has been markedly improved within the
      last few years. This emphasizes the importance of determining prognostic markers
      in each patient. A specific genetic diagnosis may prove to be of major
      importance.

PMID- 9763920
TI  - [Risk factors for epidermoid carcinoma of the vulva].
AB  - There is mounting evidence that epidermoid carcinoma of the vulva may be divided
      into two aetiologically distinct categories. One category, that is closely linked
      to infection with high-risk types of human papillomaviruses, comprises
      malignancies whose histological picture is either basaloid or warty carcinoma.
      Another category, keratinizing squamous cell carcinoma, has a much weaker
      association with human papillomaviruses and occurs mainly in elderly women. This
      review describes the current status with regard to risk factors for epidermoid
      carcinoma of the vulva.

PMID- 9763921
TI  - [Bacteremia in children with acute lymphoblastic leukemia].
AB  - The purpose of this study was to describe the pattern of bacterial infections in
      children with acute lymphoblastic leukemia. Forty-six children with ALL were
      treated for 119 febrile episodes. Antibiotic therapy was initiated with
      ampicillin and gentamicin, +/- dicloxacillin and lasted for 5-8 days. Bacterial
      cultures were positive in 36 of 119 febrile events. At the beginning of the
      febrile disease there was no difference in CRP and neutrophil count between
      children with positive and negative blood cultures. The maximum CRP was, however,
      significantly higher in children with positive blood cultures. In 75% there was
      no need to change the initial antibiotic treatment with ampicillin and gentamicin
      +/- dicloxacillin. If the temperature has been normal for 2-3 days and the
      neutrophil count is increasing it appears safe to discontinue the antibiotic
      therapy after five days when blood cultures are negative and after 7-8 days when
      cultures are positive.

PMID- 9763922
TI  - [Information to young people about HIV/AIDS and drug abuse. A study of the
      knowledge and use of the information material in the youth center in Copenhagen].
AB  - A mailed questionnaire was carried out in the city of Copenhagen in which the
      leaders of 106 youth centres expressed their opinion on different publications
      concerning drug abuse and HIV/AIDS. The knowledge of the publications among the
      leaders was less than expected. The last known publication was recognized by 7%
      of the leaders, the most well known by 55%. A considerable part of the leaders
      stated that they had never received the publications. In centres where the
      leaders knew of the publications they were widely used, most often in centres for
      older members. A group of leaders stated, that the publications were irrelevant
      for members aged 9-14 years. The study points out specific problems in the health
      educations process: The publication should aim more specifically at the group and
      at subpopulations in the group. The distribution should be secured and the
      knowledge of the supply of health education material among the leaders of the
      youth centres should be raised.

PMID- 9763923
TI  - [Treatment of hypertrophic cardiomyopathy].
AB  - The medical management of hypertrophic cardiomyopathy is reviewed. Four cases of
      hypertrophic cardiomyopathy are presented, and serve to describe the currently
      available invasive treatment modalities, i.e. septal myectomy, dual chamber
      pacing, cardioverter defibrillator implantation and heart transplantation. These
      different invasive treatments all seem to be symptomatically effective in
      carefully selected patients, but studies of prognostic effects are not available.
      Finally, new experimental procedures are presented.

PMID- 9763924
TI  - [Umbilical cord blood as a biological spare part. Experiences from a pilot
      project] at the Fredericia hospital].
AB  - The haematopoietic stem cells remaining in the placenta after the umbilical cord
      has been cut can substitute for bone marrow in transplantations. It is argued
      that these cells should be retrieved and kept frozen as the child's personal
      biological spare part. A pilot, population-based collection of cord blood was
      carried out in a small provincial in Denmark. It was found that the pregnant
      women supported the concept (89%), that the midwives and technicians could carry
      out sampling and freezing after a short instruction period, and that the cost of
      sampling and storing for 75 years approx. DKK 12,000 per child. The project group
      is now seeking partners for further development of the concept.

PMID- 9763925
TI  - [Prognosis of hematological patients with relapse following high-dose
      chemotherapy and autologous stem cell transplantation].
AB  - A retrospective analysis of the outcome for 283 haematological patients who
      relapsed after high dose chemotherapy and autologous stem cell transplantation
      during a five year period from 1989 to 1994 is presented. The patients were
      treated in accordance with local regimes at 20 Nordic transplantation centers and
      included patients with acute leukemia (157 patients), multiple myeloma (16
      patients) and lymphoma (110 patients). Two hundred and twenty-nine patients with
      relapse or progressive disease were given chemo- and/or radiotherapy and the
      response was evaluated after 90 days. Fifty-four patients (24%) obtained a
      complete remission and 44 patients (19%) partial remission. The overall median
      survival after relapse was five months. In the group who received salvage
      treatment the median survival was seven months, and for the 54 patients in
      complete remission the median survival was 15 months. We found that survival
      after relapse depends upon primary disease, the time from transplantation to
      relapse and whether salvage therapy was initiated.

PMID- 9763926
TI  - [Mortality of anorexia nervosa in Denmark 1970-1987].
AB  - Eight hundred and fifty-three patients were admitted to psychiatric institutions
      in Denmark with anorexia nervosa between 1970 and 1986. Based on register
      information, 50 deaths were recorded during a mean follow-up period of 7.8 years.
      Amongst these, five were males and 45 females. The standardized mortality ratio
      (SMR) was 9.1 in both sexes. The SMR was maximal during the first year after
      index admission. Suicide was the dominant cause of death amongst subjects who
      died from unnatural causes (18 of 22 cases). Among those who died from natural
      causes (24 subjects), 13 individuals died from anorexia nervosa, and 11
      individuals died from other illnesses.

PMID- 9763927
TI  - [Amebiasis--a differential diagnosis from inflammatory bowel disease].
AB  - Entamoeba histolytica is a very uncommon etiology of travelers diarrhoea, but may
      be an important differential diagnosis to inflammatory bowel disease. A
      misdiagnosis of amoebic colitis as inflammatory bowel disease followed by
      inadvertent treatment with corticosteroids may be fatal. Current techniques for
      the diagnosis of amoebiasis include stool studies, endoscopic biopsy and
      serology. Demonstration of haematophagous trophozoites in feces or in tissue
      biopsy is the definitive method for diagnosis. Unfortunately both methods have
      many drawbacks. If the specimens are negative, serology can support the diagnosis
      especially in a non-endemic area where a positive test is highly predictive of
      current disease.

PMID- 9763928
TI  - [Contact eczema caused by pine wood].
AB  - A 34 year-old woman, working with pine wood treated with sodium hydroxide and
      pyrogallol, developed dermatitis on arms, face and neck. Patch testing showed
      allergic reaction to colophony and pine wood, but not to sodium hydroxide or
      pyrogallol. Pine wood contains colophony. Since avoiding pine wood, she has had
      no further attack of dermatitis.

PMID- 9763929
TI  - [Malignant transformation of Recklinghausen disease in the small intestine].
AB  - Neurofibromatosis is a relatively common genetic disorder of the peripheral and
      central nervous systems. Benign or malignant tumours may occur in different
      organs. Visceral tumours arising in the neural plexus of the intestinal wall may
      cause ulceration, bleeding, obstruction, perforation and palpable abdominal
      masses. In this paper a case of chronic anaemia due to a chronically bleeding
      intestinal neurofibroma is presented in a woman who had undergone intestinal
      resection. Histopathological analysis showed a neurofibroma with malignant
      transformation and a liver metastasis.

PMID- 9763930
TI  - [Quality is more important than structure].

PMID- 9763931
TI  - Legionnaires' disease in Europe, 1997.

PMID- 9763933
TI  - Antituberculosis drug resistance worldwide.

PMID- 9763932
TI  - Murine typhus, Portugal.

PMID- 9763934
TI  - RABNET-strengthening international surveillance of human and animal rabies.

PMID- 9763935
TI  - Dengue in the WHO Western Pacific Region.

PMID- 9763936
TI  - Aseptic meningitis due to echovirus 30, Japan, 1997-1998.

PMID- 9763937
TI  - A fight on our hands.

PMID- 9763938
TI  - Invisible women.

PMID- 9763939
TI  - Helping Asian women to understand the menopause.
AB  - Language barriers and cultural differences isolate Asian women from the facts
      concerning menopause and HRT. Zubeda Sarwar discusses the results of a study set
      up to address these issues.

PMID- 9763940
TI  - Detecting and preventing postnatal depression.
AB  - Usually only a quarter of postnatal depression cases are identified. Jo Borrill
      discusses the role of nurses in detecting depression in mothers and giving them
      support.

PMID- 9763941
TI  - Coping with common catheter care problems.

PMID- 9763942
TI  - Nurses' involvement in the care of children with eczema.

PMID- 9763943
TI  - Giving advice on HRT: a closer look at your role.

PMID- 9763944
TI  - Traveller's diarrhoea.

PMID- 9763945
TI  - The role of protocols in enhancing nursing care.

PMID- 9763946
TI  - Delivering pressure sore care in the community.

PMID- 9763947
TI  - The correct use of low-adherent dressings.

PMID- 9763948
TI  - Going Dutch on health care.

PMID- 9763949
TI  - Strike while the iron's hot.

PMID- 9763950
TI  - Twilight zones.

PMID- 9763951
TI  - A fast service from nurses.

PMID- 9763952
TI  - Vitamins and health: the role of a balanced diet.

PMID- 9763953
TI  - Using spirometers: taking a blow for good health.

PMID- 9763954
TI  - Prostate disease: expanding the nurse's role.

PMID- 9763955
TI  - Remedies for athlete's foot.

PMID- 9763956
TI  - Approaches to managing diabetes in Asian people.
AB  - The prevalence of diabetes is four times higher in people of Asian origin than in
      Caucasians. Mary Burden discusses how the management of diabetes differs in
      Asians.

PMID- 9763957
TI  - Hepatitis: reducing the risks.

PMID- 9763958
TI  - Why nurse prescribing is good for you....

PMID- 9763959
TI  - Leg ulcers: finding solutions to common problems.

PMID- 9763960
TI  - Deodorising dressings for malodorous wounds.

PMID- 9763961
TI  - It'll be all right on the night....

PMID- 9763962
TI  - Let's focus on the real issues.

PMID- 9763963
TI  - Harsh cuts.

PMID- 9763964
TI  - Phobias: when the fear just gets too much.

PMID- 9763965
TI  - Role of allergies in eczema.
AB  - Contact allergies have an important role to play in eczema. Justine Ratcliffe
      considers how detection of the causative allergen by patch testing can improve
      disease management

PMID- 9763966
TI  - Contraception: let's put men in the picture.

PMID- 9763967
TI  - A cover-up operation to target sunseekers.
AB  - Although the link between sun and skin cancer is well known, many people still
      ignore this fact in the pursuit of a 'healthy' tan. Jackie Cresswell highlights
      the dangers and looks at the risks.

PMID- 9763968
TI  - Urinary tract infections: the hidden cause.
AB  - Urinary infections are a common problem mainly affecting women. Deborah Rigby
      outlines their causes and symptoms, and describes how they can be avoided.

PMID- 9763969
TI  - Group protocols and the law.

PMID- 9763970
TI  - Methods of effective pain management in adults.

PMID- 9763971
TI  - The orf virus: a disease of the farming community.

PMID- 9763972
TI  - Reaping the benefits of foam dressings.

PMID- 9763973
TI  - Setting up a stoma care service.

PMID- 9763974
TI  - A force to be reckoned with.

PMID- 9763975
TI  - Landmarks in diabetes care: a historical perspective.
AB  - Since the discovery and isolation of insulin in 1921, many advances in diabetes
      research and management have been made. Funda Suleyman charts the successes over
      the years.

PMID- 9763976
TI  - Strategies to promote healthier eating.

PMID- 9763977
TI  - A new treatment option in asthma management.
AB  - For the first time in 20 years a new therapeutic option in asthma management has
      emerged. Christine Fehrenbach discusses the role of leukotriene receptor
      antagonists in asthma care.

PMID- 9763978
TI  - The NHS--taking a look back.

PMID- 9763979
TI  - Vaccines: the role of the NHS.

PMID- 9763980
TI  - Pushing back the boundaries: administration of medicines.

PMID- 9763981
TI  - The dying art of bandaging.

PMID- 9763982
TI  - Role of swabbing in wound infection management.

PMID- 9763983
TI  - Targeting teenage asthmatics.

PMID- 9763984
TI  - A timely booster.

PMID- 9763985
TI  - A positive effect.

PMID- 9763986
TI  - Impact of osteoporosis on quality of life.
AB  - Osteoporosis is now a major public health problem that affects men as well as
      women, resulting in pain, bone fractures and premature death. Anne Sutcliffe
      explains the nurse's role in treatment and prevention.

PMID- 9763987
TI  - Dealing with nocturnal enuresis in children.

PMID- 9763988
TI  - Helping people to remain in control of their psoriasis.
AB  - The impact of psoriasis on the quality of life cannot be overestimated. Jane
      Watts outlines the various forms of this skin condition and describes the nurse's
      role in its management.

PMID- 9763989
TI  - Screening for diabetes: how to make a diagnosis.
AB  - The classification of diabetes into different types is not always
      straightforward. Mary Burden explains the role of screening procedures in making
      an effective diagnosis.

PMID- 9763990
TI  - Nutrition and wound healing.

PMID- 9763991
TI  - When to use film dressings.

PMID- 9763992
TI  - Good health through nutrition.

PMID- 9763993
TI  - Medication management in residents of aged care facilities.
AB  - Responding to the medication needs of an ageing population is a major challenge
      for the Australian health care system. As the main care givers of residents in
      aged care facilities, nurses are ideally positioned to promote quality medication
      management for these individuals. This review paper identifies issues affecting
      medication management of elderly residents, using the psychotropic family of
      drugs as an example. Strategies aimed at improving medication management in
      elderly residents, which include education, guidelines documents, legislation and
      consumer medication information, are also examined. While the review explores the
      nurse's perspective, it also emphasises the need for collaborative involvement.

PMID- 9763994
TI  - National palliative care education and training needs analysis.
AB  - This purpose of this research study was to conduct a needs analysis for the
      education and training of palliative care providers. The research methodology was
      a descriptive survey of the education and training needs of palliative care
      providers. A total of 1848 questionnaires was distributed to the palliative care
      providers throughout Australia and a return rate of 34 per cent (627) was
      attained. The responses from Australia metropolitan areas totalled 51.7 per cent
      and those from Australian rural and remote areas totalled 48.3 per cent (302).
      The results showed that the specific education and training needs, as identified
      by the palliative care providers, included pain management, loss and grief, drug
      therapies, education updates and other needs. Deficiencies of current education
      and training programs in palliative care included cost as most postgraduate
      courses are not HECs funded but are offered as full fee-paying courses. Travel
      and distance were reported as the most prohibitive aspect to attending a
      palliative care course. The content in existing palliative care programs
      predominantly focused on providing care in a palliative care unit or a respite
      setting. More emphasis needs to be placed on caring for patients in their home; a
      shift from death in the hospital to death in the home.

PMID- 9763995
TI  - A conceptual framework for nursing management of pain.
AB  - The development of specific nursing-based conceptual frameworks help to define
      and link ideas when performing studies involving a number of different concepts.
      Through the use of nursing models and frameworks, knowledge gained from nursing
      research can be more readily disseminated into nursing practice. The present
      framework encompasses nurses' knowledge and attitudes about pain management and
      incorporates the work of many theorists, the most prominent being that of Brenda
      Conrad. This pain management scheme expresses the belief that nurses have a
      unique and pivotal role in supporting and promoting optimum health states and
      providing quality life. It generates overall goals related to nurse assistance of
      the patient in the areas of recovery, independence, adjustment and treatment, and
      emphasises that to meet the patient's needs, nurses must possess adequate pain
      assessment and management knowledge as well as supportive attitudes to provide
      efficient quality care provision. The major supposition emphasised throughout
      this conceptual framework is that underlying nursing care is a grounded knowledge
      base fostering genuine care and concern for the welfare of the holistic patient.

PMID- 9763996
TI  - Non-compliance or client control?

PMID- 9763997
TI  - Undergraduate Clinical Practicum and the opportunity to practice skills in
      preparation for the graduate year: a review of the literature.
AB  - Clinical Practicum is an important component of undergraduate nursing education,
      in order to prepare the graduates for their role as Registered Nurses. It is
      argued by some that in reality the Clinical Practicum experiences do not
      adequately provide graduates with the skills they need during the graduate year.

PMID- 9763998
TI  - The 'write advice' or 'how to get a journal article published'.
AB  - This paper was written in response to a perceived increase in nurses' interest in
      writing for publication in nursing journals. It provides essential information
      for inexperienced or 'beginning' writers. Who should write for publication, what
      should be written for publication and how it should be written are discussed.
      Practical details with respect to writing and rewriting are included.

PMID- 9763999
TI  - Fact sheets on the Web: a case study of the on-line dissemination of information
      on the anti-infective properties of breast milk.
AB  - As the World Wide Web expands, it is beginning to take on a new role as a
      publishing medium for authoritative encyclopaedic information. This development
      is likely to impact the way in which many professionals work--improving their
      access to up-to-date information on the one hand, while enabling their clients to
      be much better informed on the other. This article draws on the experience gained
      from publishing a small, specialised Web site providing information on the anti
      infective properties of human breast milk. It describes the way in which the Web
      site came into being, the nature and structure of the information that is
      provided, and the types of responses the site has received. The article concludes
      with a discussion of the ways in which the availability of authoritative
      information on the Web is likely to impact the future roles of health
      professionals.

PMID- 9764000
TI  - Learning with technology: use of case-based physical and computer simulations in
      professional education.
AB  - This paper describes a multimedia technology project in midwifery education and
      how it is being developed to improve student learning experiences and outcomes.
      The role of the university providing quality education relevant to today's world
      and professional practice is emphasised. A collaborative (Royal Melbourne
      Institute of Technology and Australian Catholic University) interdisciplinary
      project 'Pregnancy Simulator: Developing and Enhancing Student Learning of
      Pregnancy Assessment Skills' was developed with university and direct
      Commonwealth support. This project consists of a physical simulation of a
      pregnant woman at term and case-based multimedia computer simulations designed to
      develop and enhance student learning of abdominal assessment skills. A key
      feature of the development has been to design a learning experience explicitly on
      an authoritative theory-based view of teaching, in this case Diana Laurillard's
      'Conversational Framework'.

PMID- 9764001
TI  - On nursing's 'reflective madness'.

PMID- 9764002
TI  - Exploring women's experiences: the critical relationship between nursing
      education, peer mentoring and female friendship.
AB  - A research study was conducted in 1995 with seven women nurses from Southern
      Cross University, Australia. The aim of this research was to investigate the
      possible relationship between female friendship, mentoring and nursing education.
      The researchers comprised six second-year nursing degree students and the
      programme co-ordinator for the Bachelor of Nursing programme. This research was
      framed in an emancipatory paradigm of critical social science and feminist
      theory. Reflective journalising and interviewing were used as the research
      methods. The results indicated that there is an inextricable link between female
      friendship and peer mentoring. These two 'features' created a productive climate
      for shared learning, shared caring, reciprocity and commitment to one another's
      personal and professional growth.

PMID- 9764003
TI  - Nurses as patient-teachers: exploring current expressions of the role.
AB  - An exploration of nursing literature reveals a broad acceptance of the role of
      patient-teacher. While patient-teaching has become widely accepted as part of
      nursing practice, there is little published evidence to support an assertion of
      its centrality in current nursing practice. Patient-teaching has been variously
      described, yet there is evidence of polarity in its construction. This polarity
      is between a health promotion empowerment framework and a mechanistic
      interventionist framework. Further, there is little visible consensus about the
      scope and boundaries of patient-teaching by nurses. Preliminary findings from a
      pilot study of nurses' perceptions of patient-teaching reveal tensions created
      within these contradictory frameworks. Nurses find themselves positioned as
      paternalistic in their approach to patients and simultaneously subservient to
      other disciplines in determining the focus of patient-teaching.

PMID- 9764004
TI  - Massage as a nursing intervention: using reflection to achieve change in
      practice.
AB  - The process of reflection can be used by nurse educators to more fully understand
      the nature of nursing practice and to actively use that understanding to bring
      about change through education. This paper documents a process of reflection
      carried out by a nurse educator within an action research project. The project
      was intended to assist palliative care nurses to learn the skill of massage and
      successfully integrate this therapy into their practice. Reflection takes place
      before the action to achieve change is implemented, in order to identify factors
      which will affect the development and implementation of the project. The
      reflection includes discussion of methodological issues, consideration of the
      influence of massage and holism in nursing practice and the influence of practice
      and institutional factors on palliative care nursing.

PMID- 9764005
TI  - Caring by degrees.
AB  - Caring is synonymous with nursing and, regardless of the culture, race, lifestyle
      or sexuality of clients, nurses should care for all clients. However, the
      emergence of HIV/AIDS brought a new and quite different challenge to nurses with
      regard to willingness to care. Some nurses expressed a negative attitude toward,
      and reluctance to care for, those clients with HIV/AIDS, mainly due to fear of
      contagion based on ignorance about the disease. The purpose of this cross
      sectional study was firstly to determine if there were differences in attitudes
      toward caring for clients with HIV/AIDS in the three different at-risk groups
      (homosexuals, intravenous drug users and haemophiliacs), as expressed by nursing
      students at the beginning (Semester 1) and at the end (Semester 7) of a three-and
      a-half-year nursing degree programme. The second determination was whether or not
      there were differences between the two groups of students regarding their
      knowledge of HIV/AIDS. Data results indicated no significant difference between
      the two groups of students in regard to caring attitude towards members of the at
      risk groups and knowledge of AIDS. This paper discusses the implications of the
      research findings for nursing and further research.

PMID- 9764006
TI  - Dilemmas in nursing care: a student's reflection of a critical incident.
AB  - A student nurse will face many questions when they are confronted with the death
      of a patient. In this paper, a first-year nursing student reflects upon the death
      of a young adult (Yvonne) as part of a nursing inquiry subject. The author
      reflects upon the death of Yvonne and re-examines the questions and responses
      that this critical incident raised.

PMID- 9764007
TI  - Learning with technology: use of case-based physical and computer simulations in
      professional education.
AB  - This presentation will clarify contemporary ideas on the role of technology in
      education and how it can be employed to improve student learning experiences and
      outcomes. The paper will emphasise RMIT's role in providing quality education
      that is relevant to today's world and professional practice. It will examine a
      specific collaborative (RMIT & ACU), interdisciplinary project 'Pregnancy
      Simulator: Developing and Enhancing Student Learning of Assessment Skills'. This
      project consist of a physical pregnancy model connected to a multi-media computer
      assisted learning package for the purpose of enhancing student learning of
      abdominal assessment skills. Our paper outlines an innovative technology-based
      teaching project and includes current educational issues or problems encountered
      in professional education, steps already taken to address these difficulties and
      how this project intends to facilitate learning. It identifies expected learning
      outcomes for midwives, nurses and medical students, and examines pedagogical
      principles applied to technological applications designed to provide guided
      discovery for allowing students to build confidence and competence in
      professional education. The case-based physical and computer simulations
      contextualise learning to assist transfer of learning to real world situations.
      This paper will also discuss how technology-based projects can be evaluated and
      integrated into university curricula to enhance student learning.

PMID- 9764008
TI  - Should nurses act legally or ethically?
AB  - Should health professionals act legally or ethically in the delivery of health
      care presuming it is impossible to do both? There is a tendency by some to take
      the position that to act ethically is more important in the provision of health
      care and to ignore or at least minimise any legal consequences that may arise. At
      the same time the law may ignore ethical principles claiming the legal position
      is more important. This article argues that while law and ethics are both
      important in the delivery of health care the law as the final arbitrator takes
      precedence.

PMID- 9764009
TI  - Acute renal failure. Focus on advances in acute tubular necrosis.
AB  - This article has reviewed the most recent thoughts and findings on the
      pathophysiology and care of ARF. Clearly, we still have much to learn, but an
      updated practitioner is necessary in order to meet the challenges of this complex
      disease, as we search for tomorrow's answers.

PMID- 9764010
TI  - Continuous renal replacement therapy. A national perspective AACN/NKF.
AB  - Health care providers rely on quality continuing education programs to increase
      their knowledge and to acquire new skills. Participation in programs such as
      CVVH: Implications for Clinical Practice-the Patient, the Circuit, the Team can
      potentially improve patient outcomes. While this study identifies critical care
      nurses as a receptive professional group for further CRRT training, it also
      indicates that additional education in this topic may benefit other members of
      the critical care team as well. Therefore, because the critical care nurse's
      role, while crucial to the clinical management of patients undergoing CRRT, does
      not include prescribing or initiating CRRT therapy, it is difficult to predict
      the impact of future workshops on the increased and sustained use of CRRT in
      critical care arenas. If you would like additional information on CVVH:
      Implications for Practice-the Patient, the Circuit, the Team, please contact the
      National Kidney Foundation at (800) 622-9010, or the American Association of
      Critical Care Nurses at (800) 899-2226.

PMID- 9764011
TI  - CAVH. Principles and practical applications.
AB  - While being one of the earliest and simplest forms of continuous renal
      replacement therapy, CAVH provided a means for treating the azotemic,
      hypervolemic critically ill patient. In order to deliver care for the patient
      undergoing CAVH, critical care nurses must demonstrate an understanding of the
      physiologic mechanism of action as well as knowledge and technical competency
      regarding circuit management. Multidisciplinary standards are imperative for
      successful implementation of any CRRT program. Any institution wishing to adopt
      certain CAVH standards provided within this article should review each particular
      standard to determine if it meets the specific needs of their unique patient
      population.

PMID- 9764012
TI  - CAVHD. Transitioning from CAVH.

PMID- 9764013
TI  - Adult/pediatric CVVH. The pump, the patient, the circuit.

PMID- 9764014
TI  - Applications in continuous venous to venous hemofiltration. Interactive case
      studies in the adult patient.

PMID- 9764015
TI  - Applications in continuous venous to venous hemofiltration. Interactive pediatric
      case study.

PMID- 9764016
TI  - Continuous venous to venous hemofiltration. Implementing and maintaining a
      program: examples and alternatives.

PMID- 9764017
TI  - Setting up a continuous venovenous hemofiltration educational program. A case
      study in program development.
AB  - The key to developing a successful CVVH course is the involvement of the clinical
      experts--the staff nurses. It is an ongoing process that requires continual
      improvement. The CVVH course will help to assure the competency of the ICU nurse
      in caring for the critically ill patient on CVVH.

PMID- 9764018
TI  - Ethical decision making. Models for the dialysis dependent patient.

PMID- 9764019
TI  - Care management in a managed care world.

PMID- 9764020
TI  - Service use patterns in HIV/AIDS case management: a five-year study.
AB  - Over the course of the HIV/AIDS epidemic, the profile of the client population
      has changed. Increasingly, individuals infected with HIV identify injection drug
      use and heterosexual contact as their risk factors. Additionally, women are
      increasingly affected by the epidemic. This study examines individuals enrolled
      in an HIV/AIDS case management program over a 5-year period. Although the number
      of clients served per year remained relatively stable, the number of clients with
      injection drug use histories and the percentage of women on the caseload have
      increased consistently. The percentage of clients requiring services and the
      amount of services used increased in the areas of attendant care, mental health
      services, and skilled nursing care. Additionally, the annual mean use of services
      increased in the areas of in-home supportive services and hours of case
      management. These data suggest that as individuals receiving HIV/AIDS case
      management services are found to have complicating social and economic factors,
      their need and use of services will increase.

PMID- 9764021
TI  - Case management and supported employment: a good fit.
AB  - Individuals with severe disabilities have often been denied the full range of
      vocational opportunities. Because of discrimination and oppression, and false
      beliefs regarding their skills, capacities, capabilities, and interests,
      individuals with disabilities have often been relegated to nonwork activities or
      sheltered work opportunities. Passage of legislation, such as the Developmental
      Disabilities Assistance and Bill of Rights Act of 1984 and Title VI, Part C of
      the Rehabilitation Act Amendments of 1986, in combination with systems change
      grants funded through Title III of the Rehabilitation Act, provided the basis for
      the initiation of a series of federal- and state-funded demonstration projects
      designed to provide opportunities and supports for individuals with severe or
      significant disabilities to work at competitive sites in the community. This
      model of vocational services, called supported employment, while initially
      conceived as a vocational program for individuals with mental retardation, has
      been modified to successfully provide services to individuals with mental
      illness, acquired brain injury, autism, cerebral palsy, physical disabilities,
      and other disabilities. A key to the success of these programs is the
      complementary working relationship between the case manager and the job coach.
      While there may be some overlap in what each brings to the person with a
      disability, each professional plays distinctive and critical roles in the
      carrying out of supported employment.

PMID- 9764022
TI  - Designing an automated services tracking system for a caregiver support program.
AB  - This article describes the process of developing an automated services tracking
      system for California's 11 regional Caregiver Resource Centers. The system was
      designed over a 3-year period for use by social workers, administrative
      personnel, and managers and has implications for both internal services
      monitoring and state reporting functions. The system development included input
      from clinical staff to be user-friendly to nontechnical staff. The article
      recounts technical and conceptual obstacles overcome and the evaluation of a
      relatively modest idea into a sophisticated, custom-made computer program. Issues
      of start-up, implementation, expansion, and report design are discussed. Lessons
      learned and other insights have practice and policy implications for documenting
      and reporting service usage at case management and other social services
      agencies. Lastly, an overview of the system's features and highlights of
      automated reports are provided.

PMID- 9764023
TI  - Giving and receiving social supports for elderly mentally ill people.
AB  - Two research questions were addressed in this study of 57 older adult outpatients
      diagnosed with schizophrenia and 37 older adults attending a senior citizen's
      center with no significant medical or psychological problems. The research
      questions were: (a) Are there gender-based differences in giving and receiving
      expressive and instrumental social supports for chronically mentally ill
      patients? (b) Do chronically mentally ill elderly patients differ from older
      adults without chronic mental illness in giving and receiving expressive and
      instrumental social supports? Based on a two-factor multi variate analysis of
      variance, women, with or without diagnosis of chronic mental illness, were more
      likely than were men to provide emotionally close social contacts with others, as
      well as to give advice to and receive advice from others. However, there were no
      differences in giving or receiving instrumental or expressive social supports
      based on whether or not the respondent was receiving outpatient psychiatric
      services for a chronic mental illness. In view of this, the possibility that the
      mentally ill have more to offer in relationships than is generally assumed is
      discussed. Suggestions for future research and implications for case managers
      also are discussed.

PMID- 9764024
TI  - Case management for the baby boom generation: a strengths perspective.
AB  - To understand the challenges and opportunities for case management as the turn of
      the century approaches, we must consider the 76 million individuals born between
      1946 and 1964, commonly referred to as the baby boom generation. This article
      examines the baby boom generation in the context of planning effective case
      management services. The generation's strengths are highlighted to suggest how
      case management systems can meet the anticipated service needs of baby boomers as
      they age.

PMID- 9764025
TI  - An empirical study of nursing in patients undergoing two different procedures for
      abdominal aortic aneurysm repair.
AB  - Specialized vascular nursing has to meet the challenge presented through progress
      and modern developments in vascular surgery. Endovascular techniques are becoming
      more widespread and are now available for diseases that previously have required
      extensive surgery. A comparative study was carried out in two groups of patients
      with infrarenal abdominal aortic aneurysms (N = 50), either by means of the
      traditional open surgical approach or by the new endovascular stented graft
      technology. Four problems were compared in both groups of patients: (1) length of
      hospital stay, (2) dependency on nursing, (3) patients mobility after surgery,
      and (4) analgesic requirements. Data were obtained from a designated data sheet.
      Analysis of the data obtained helped us in our service to optimize the nursing
      process for patients undergoing major aortic surgery for open, as well as
      endovascular, procedures, especially regarding the nursing anamnesis and nursing
      diagnosis.

PMID- 9764026
TI  - Polytetrafluoroethylene femorodistal grafts: can the use of a vein collar offer
      patients a reasonable chance of success?
AB  - The growing number of patients with critical ischemia who lack a suitable
      autogenous vein for grafting pose a particular problem for the vascular team. In
      such patients the use of a polytetrafluoroethylene graft with a distal
      anastomotic vein cuff or patch has been advocated as an alternative to primary
      amputation. The use of such adjunctive techniques is reviewed through a 3-year
      retrospective study of 50 patients under the care of one surgeon. Data analyzed
      include patient demographics, risk factors, and presenting symptoms. All patients
      were included in a Duplex graft surveillance program. The cumulative patency
      rates at 1 and 2 years were 56% and 55%, respectively, with limb salvage rates of
      85% and 80%. The data support a reconstructive approach to maintain the quality
      of the patient's life.

PMID- 9764027
TI  - Experience with a new human skin equivalent for healing venous leg ulcers.
AB  - Leg ulcers affect about 650,000 adults each year and in every setting--rural,
      urban, and both economically developed and impoverished areas. Both the physical
      and the psychologic aspects of treatment present challenges to the caregiver. The
      nurse must be aware of new techniques for treatment and be able to educate
      patients about potential modalities for healing. A human skin equivalent,
      Apligraf, will soon be available for treatment of these wounds. The results of
      controlled, multicenter studies indicate that human skin equivalent interacts
      with the patient's own cells, responds to individual wound characteristics, and
      promotes healing. The nursing professional can readily master the application
      technique and will find that this tissue-engineered skin product offers a new
      approach to wound management.

PMID- 9764028
TI  - Impact of telephone reinforcement of risk reduction education on patient
      compliance.
AB  - Smoking and hyperlipidemia are key risk factors resulting in peripheral arterial
      disease. These risk factors can be reduced when appropriate lifestyle changes are
      made, especially for patients less than 60 years of age. Therefore patient
      education regarding smoking cessation and healthy diet changes may positively
      impact the course of disease. The ability to make a lifestyle change is affected
      by (1) an individual's belief that his or her behavior affects the condition and
      (2) the social support received from family, especially a primary caregiver. This
      pilot study compared two randomized groups of patients with peripheral arterial
      disease for a 1-year period. The control group received the standardized teaching
      plan regarding smoking cessation and diet at the postoperative clinic visit. The
      experimental group received the standardized teaching plan in addition to
      quarterly telephone calls to reinforce smoking cessation and diet information. At
      the end of 1 year, both groups received follow-up telephone calls at the
      conclusion of the study for endpoint data collection. Specifically, this project
      investigated the following research statements: (1) Patients who receive periodic
      telephone follow-up will have greater compliance with the recommendations
      regarding smoking and diet than those who do not receive follow-up. (2) Patients
      whose caregivers are compliant with the recommendations regarding smoking
      cessation and diet will have significantly higher compliance themselves. The data
      were analyzed by using cross tabulation, sign test, and McNemar's test for
      nonparametric data to measure mobility, overall perception of health, knowledge
      of risk reduction information, and compliance with the smoking cessation and low
      fat/cholesterol diet plan. The results of this pilot study revealed no
      significant differences between the control and experimental groups. Telephone
      reinforcement was not sufficient in this study to influence lifestyle change.
      However, standardized teaching improved diet scores in both groups. Differences
      were found between smokers and nonsmokers.

PMID- 9764029
TI  - United Kingdom guidelines for the management of acute pancreatitis. British
      Society of Gastroenterology.

PMID- 9764030
TI  - Bacterial factors and immune pathogenesis in Helicobacter pylori infection.
AB  - Virulent Helicobacter pylori strains which have been clinically associated with
      severe outcome induce increased gastric mucosal immune responses. Although
      several bacterial pathogenic factors have been shown to have a considerable role
      in H pylori infection, variability in host immune responses may also contribute
      to mucosal damage in H pylori associated gastritis.

PMID- 9764031
TI  - Helicobacter pylori: the size of the problem.

PMID- 9764032
TI  - Management of Helicobacter pylori infection in children.
AB  - When trying to decide which children with Helicobacter pylori infection should be
      treated and at what stage they should be tested, we should take into account the
      fact that eradication of the infection may be useful both to induce symptom
      remission and to prevent later complications in adulthood. However, well designed
      studies to identify those infected children who are at risk of developing
      complications or have symptoms due to the infection are still lacking. Current
      literature only gives information on how to treat children with H pylori
      infection. Treatment regimens that include two drugs are usually more effective
      than in adults, and produce an eradication rate of 70-80%, but they should be
      given for at least two weeks, shorter treatments being less effective. Antibiotic
      resistance can impair eradication rate and the frequency of resistant strains in
      children should be studied. Combinations of antibiotics with antisecretory drugs
      are highly effective in adults, but triple therapy with two antibiotics and an
      antisecretory drug has been seldom tried in children; compliance is often poor so
      that the eradication rate is often similar to that produced by dual therapy.
      Compliance strongly influences eradication, and short simple treatment regimens
      that produce rapid symptom remission with few side effects are needed to optimise
      patient compliance. After treatment, eradication must be proved. Serological
      tests can help, provided that pretreatment serum is available and three to six
      months have passed since the treatment. A 13C-ureabreath test (13C-UBT) should be
      performed at least six weeks after treatment, but false negative results can
      occur and cut-off must be adjusted.

PMID- 9764034
TI  - Management of dyspeptic patients by general practitioners and specialists.

PMID- 9764033
TI  - Different management for Helicobacter pylori positive and negative patients with
      gastro-oesophageal reflux disease?
AB  - Available evidence would suggest that Helicobacter pylori infection does not
      contribute to the pathogenesis of gastro-oesophageal reflux disease. The
      prevalence of H pylori infection in patients with reflux disease is no greater
      than that in control populations. There are some data suggesting that the
      organism has a protective role: patients with duodenal ulcers develop reflux
      disease after H pylori eradication, whereas in patients with oesophageal reflux
      those with H pylori infection have less severe reflux changes. There is also
      evidence indicating that the presence of H pylori augments the anti-secretory
      properties of both the H2 receptor antagonists and proton pump inhibitors (PPIs),
      suggesting that eradication therapy may not be beneficial. However, the
      considerable recent interest in the association between H pylori and reflux
      disease has largely been generated by studies outlining the interactions between
      H pylori infection and acid suppression in the long term. In H pylori positive
      patients, therapy with PPIs is associated with a proximal extension of the
      infection and its associated gastritis. In addition long term PPI therapy is
      reported to be associated with an accelerated development of atrophic gastritis,
      suggesting that H pylori should be diagnosed and treated. Although these latter
      findings in particular need confirmation, H pylori eradication therapy should be
      considered in this patient group, at least until there is evidence to the
      contrary.

PMID- 9764035
TI  - Treatment of Helicobacter pylori infection: management of patients with ulcer
      disease by general practitioners and gastroenterologists.
AB  - Knowledge of the importance of Helicobacter pylori infection is still
      fragmentary. Currently only a minority of patients with ulcers receive adequate
      eradication therapy. Ideally there should be no difference in the level of
      knowledge between general practitioners and gastroenterologists. Yet in practice
      there is a substantial difference. The results obtained in highly selected
      clinical trials do not reflect results of practice in the real world. The gap can
      only be narrowed through careful mass education. The role of testing for H pylori
      infection in primary care practice needs to be clarified and the problem of
      erratic treatment by general practitioners and specialists needs to be resolved.
      Adequate response to these problems will require the creation of "regional
      platforms" where both primary care physicians and specialists decide on empirical
      therapy, eradication strategy and referral of dyspeptic patients.

PMID- 9764037
TI  - Helicobacter pylori: the gastric cancer problem.

PMID- 9764036
TI  - Importance of changes in epithelial cell turnover during Helicobacter pylori
      infection in gastric carcinogenesis.
AB  - The role of Helicobacter pylori in gastric carcinogenesis is supported almost
      exclusively by epidemiological data and prospective histopathological studies.
      From biological and molecular points of view, there is no evidence that H pylori
      or its cytotoxic products have any mutagenic effects. Nevertheless, this
      infection is associated with profound changes in the pattern of epithelial cell
      turnover in gastric glands, though the importance of these changes in gastric
      carcinogenesis is still controversial. H pylori infection increases cell
      proliferation and alters the distribution of cycling cells within these glands,
      but these changes can be reversed by successful eradication of the infection.
      Apoptosis seems to be increased in gastric epithelial cells during H pylori
      infection, as shown by in vitro studies. There is some, though no conclusive,
      evidence that this finding also occurs in H pylori positive subjects. It seems
      that cagA status influences the effect of H pylori on epithelial apoptosis in
      infected patients. An association of in vitro H pylori induced apoptosis with
      changes in the expression of pro- and anti-apoptotic genes is reported in the
      literature, but further study is necessary to clarify the effect of H pylori
      infection on the molecular events of the apoptotic pathway.

PMID- 9764038
TI  - Acid suppression and gastric atrophy: sifting fact from fiction.
AB  - Prolonged pharmacological acid suppression is associated with various
      histological changes in the gastric mucosa, particularly in Helicobacter pylori
      infected patients. In a number of subjects these changes include a shift in the
      gastric inflammation from the antrum to the corpus. This finding has been
      interpreted as gastric atrophy, and the possibility that acid suppression
      accelerates the progress of lesions that may lead to gastric cancer has been
      considered. Two recent studies on the relation between treatment with proton pump
      inhibitors and atrophic gastritis have yielded apparently contradictory results.
      These studies are reviewed in detail here and some of the possible reasons for
      the discrepant conclusions are explored. In particular, the way the terms
      "gastric atrophy" and "atrophic gastritis" are used is examined critically.

PMID- 9764040
TI  - Urea breath tests in the management of Helicobacter pylori infection.
AB  - The 13/14C-Urea breath test (UBT) is based on the simple principle that a
      solution of isotopically labelled urea will be rapidly hydrolysed by the
      abundantly expressed urease of H pylori. The released 13/14CO2 is absorbed across
      the mucus layer to the gastric mucosa and hence, via the systemic circulation,
      excreted in the expired breath. Distribution of urea throughout the stomach
      prevents sampling error and allows semiquantitative assessments of the extent of
      H pylori infection. Originally the 13C-UBT was complex, cumbersome and costly
      but, by simplifying the protocol and reducing the number of samples to be
      analysed, is now a much easier, quicker and cheaper test for detecting H pylori.
      Although mass spectrometry is needed for analysis of exhaled 13CO2, the use of
      the stable isotope, which is completely safe, provides advantages over the 14C
      UBT using radioactive 14C-urea, such that it can be used in women and children
      and a user's licence is not required. The widespread availability of scintigraphy
      for 14CO2 analysis may make the 14C-UBT seem an attractive alternative to the 13C
      UBT. However, there are no standard protocols for the 14C-UBT and although the
      methods are similar, several different cut off values are used which makes formal
      validation studies still necessary. Both tests are easy to perform with minimum
      opportunity for observer variation or methodological error; they are very
      sensitive and specific tests and provide a clinical "gold standard" against which
      the accuracy of other tests can be validated. The 13/14C-UBT detects only current
      infection and can be used to screen for H pylori infection and as the sole method
      for assessing eradication. In addition, because the 13C-UBT can be performed
      repeatedly in the same subject, it can be used to monitor the effects of novel
      anti-H pylori therapies and for epidemiological studies in children.

PMID- 9764039
TI  - Blood tests in the management of Helicobacter pylori infection. Italian
      Helicobacter pylori Study Group.
AB  - There are three main types of blood test available for the management of
      Helicobacter pylori infection: those that detect an antibody response; tests of
      the pathophysiological state of the stomach; and those that indicate an active
      infection. Enzyme linked immunosorbent assay (ELISA) based kits are the most
      numerous of the commercially available tests. Originally the kits used crude
      antigen preparations but many of the newer kits use a more purified antigen
      preparation giving increased specificity but a lower sensitivity. The
      sensitivity, specificity, and predictive values of the tests can also be affected
      by the population under test and coexistent disease in the patients. Near patient
      test kits are based on either latex agglutination or immunochromatography.
      Generally, they have low sensitivities compared with laboratory tests. Commercial
      western blotting kits have also been developed and are used to detect the
      presence of specific virulence markers. The exact role of serology in the
      management of Helicobacter infection has still to be defined, although there is
      evidence that, used as a screening procedure, it can reduce endoscopy cost and
      workload. Gastrin and pepsinogen blood concentrations may provide valuable
      information on the pathophysiological state of the stomach--for example, the
      presence of inflammation or gastric atrophy. A combination of serology and serum
      concentrations of gastrin and pepsinogen may be used effectively to detect
      serious gastroduodenal disease in patients.

PMID- 9764041
TI  - Any role left for invasive tests? Histology in clinical practice.

PMID- 9764042
TI  - The life and death of Helicobacter pylori.
AB  - The ability of Helicobacter pylori to survive in the varying acidity of the
      stomach is considered to be linked to its ability to maintain a tolerable pH in
      its periplasmic space by acid dependent activation of internal urease activity.
      Whereas survival of H pylori can occur between a periplasmic pH of 4.0 to 8.0,
      growth can only occur between a periplasmic pH of 6.0 to 8.0. When urease
      activity is only able to elevate periplasmic pH to between 4.0 and 6.0, the
      organisms will survive but not divide. In the absence of division, antibiotics
      such as clarithromycin and amoxycillin are ineffective. Proton pump inhibitors,
      by elevating gastric pH, would increase the population of dividing organisms and
      hence synergise with these antibiotics.

PMID- 9764043
TI  - Clinical relevance of resistant strains of Helicobacter pylori: a review of
      current data.
AB  - Acquired resistance of Helicobacter pylori to metronidazole and clarithromycin
      has been reported, with metronidazole resistance being very common. This has an
      important clinical impact on dual therapies, as well as on the standard triple
      therapies. However, when antisecretory drug based triple therapies with
      amoxycillin or clarithromycin and metronidazole are used, the resistance can be
      overcome in up to 75% of the cases in most of the studies. Clarithromycin seems
      to be a better choice than amoxycillin to achieve this goal. Nevertheless,
      resistance to metronidazole remains a risk factor for treatment failure. The most
      precise information comes from studies in which minimum inhibitory concentrations
      (MICs) are reported as well as whether the strain is susceptible or resistant.
      Few data are available from clinical trials to measure the impact of
      clarithromycin resistance. However, such resistance seems to have a negative
      impact on the clinical outcome of treatment. It is of greater importance that H
      pylori resistance is closely monitored in the future.

PMID- 9764044
TI  - The European meeting on Helicobacter pylori: therapeutic news from Lisbon.
AB  - The current standard of Helicobacter pylori treatment has been confirmed by the
      studies presented at the Lisbon workshop--that is, one of three one week proton
      pump inhibitor (PPI) based triple therapies comprising a twice daily standard
      dose of a PPI in combination with two of the following antimicrobial agents:
      clarithromycin, amoxycillin, or a nitromidazole. This standard of treatment is
      also highly efficacious and cost-effective in routine community practice. The
      current data confirm the equivalence of ranitidine bismuth citrate to PPI, and of
      azithromycin to clarithromycin. The optimum dose for azithromycin has not yet
      been defined. There is some evidence that in certain regions treatment for more
      than one week may be advantageous. The reasons are still not clear. However,
      microbial resistance may be one important factor, as it has a substantial effect
      on treatment outcome and the prevalence of resistance varies considerably in
      different areas. The negative impact of resistance is increased by shortening the
      treatment time. At present, there is no general necessity to test for resistance
      before treatment. However, before selection of a second line treatment, testing
      for resistance is recommended.

PMID- 9764045
TI  - Treatment of Helicobacter pylori: future therapeutic and prophylactic
      perspectives.
AB  - Helicobacter is one of the most widespread, chronic infections in the world and
      causes a serious disease with a significant mortality. The organism is difficult
      to eradicate using antibiotic therapy and to date no vaccine is available for use
      in humans. The most successful treatments comprise acid suppression in
      combination with two antibiotics and a series of seven day courses will reliably
      cure around 85% of infected individuals. Further modifications of these regimens
      via the introduction of newer and more effective antibiotics and acid
      suppressants may enable the treatment to be simplified, made more effective and
      cause fewer side effects. However, the major challenge is to develop a specific
      monotherapy targeted against Helicobacter pylori. The H pylori genome has now
      been sequenced and this provides an opportunity both to identify specific targets
      for drug therapy, and to facilitate the identification and production of antigens
      that may be helpful in manufacturing a vaccine. This paper discusses the future
      of helicobacter therapy and vaccination.

PMID- 9764046
TI  - Arterial or venous conduits for redo coronary artery bypass grafting?

PMID- 9764047
TI  - Heparin for coronary angioplasty: high dose, low dose, or no dose?

PMID- 9764048
TI  - Digitalis and strophanthus--cardiac glycosides.

PMID- 9764049
TI  - Angiotensin II receptor antagonists for heart failure.

PMID- 9764050
TI  - False aneurysm of the left ventricle.

PMID- 9764051
TI  - Long-term results of reoperations for recurrent angina with internal mammary
      artery versus saphenous vein grafts.
AB  - OBJECTIVE: To evaluate the long term results of coronary reoperations for
      recurrent angina with internal mammary (thoracic) arteries versus vein grafts.
      DESIGN: Inception cohort of 103 patients with a mean follow up of 7.1 years
      (range 1.0-11.6). SETTING: Regional cardiothoracic centre. PATIENTS: Among 103
      consecutive patients, mean (SD) age 61.8 (9.7) years, who were reoperated for
      recurrent angina between January 1982 and December 1991, 53 patients had
      unilateral or bilateral internal mammary artery (IMA) grafting supplemented or
      not with saphenous vein (SV) grafts (group A), and 50 patients underwent
      reoperative coronary surgery using SV grafts only (group B). The two groups were
      comparable in terms of demographic and clinicopathological data. MEASUREMENTS AND
      RESULTS: Operative mortality was 5.6% (95% confidence interval 4.6 to 6.6) for
      group A, and 10% (8.2 to 11.8) for group B (p > 0.05). Probability of freedom
      from new recurrence of angina was 86% at 5 and 10 years in group A, compared with
      56% and 25% respectively in group B (p = 0.005). Freedom from cardiac events was
      estimated to be 81% at 5 and 10 years in group A, v 52% and 20% for group B,
      respectively. Actuarial survival was 95% v 93% at 3 years, 95% v 85% at 5 years,
      and 88% v 71% at 10 years after reoperation (p > 0.05). CONCLUSIONS: The long
      term results of IMA are superior to SV grafts in terms of freedom from new
      recurrence of angina and other cardiac events. The IMA is thus the conduit of
      choice in coronary revascularisation.

PMID- 9764052
TI  - Recent activation of the plaque immune response in coronary lesions underlying
      acute coronary syndromes.
AB  - OBJECTIVE: To discriminate between chronic inflammation and acute activation of
      the plaque immune response in culprit lesions of patients with acute coronary
      syndromes. DESIGN: Retrospective study. SETTING: Tertiary referral centre.
      SUBJECTS: 71 patients having coronary atherectomy were classified according to
      their ischaemic syndrome: stable angina (n = 23); stabilised unstable angina (n =
      18); refractory unstable angina (n = 11); and acute myocardial infarction (n =
      19). MAIN OUTCOME MEASURES: Immunohistochemical measurement of interleukin 2
      receptor (IL-2R) (CD25) positive cells expressed as a percentage of the total
      amount of (CD3 positive) T lymphocytes in frozen sections of atherectomy
      specimens. RESULTS: The number of lesions containing IL-2R (CD25) positive T
      cells increased with severity of the ischaemic coronary syndrome (stable angina,
      52%; stabilised unstable angina, 77.8%; refractory unstable angina, 90.9%; acute
      myocardial infarction, 89.4%). The percentage of activated T cells (CD25/CD3
      ratios x100) increased in lesions associated with refractory unstable angina
      (7.8%) and acute myocardial infarction (18.5%), compared with those in lesions
      associated with either chronic stable angina (2.2%) or stabilised unstable angina
      (3.3%). CONCLUSIONS: An increase in the percentage of IL-2R positive T
      lymphocytes in culprit lesions of patients with acute coronary syndromes
      indicates recent activation and amplification of the immune response within
      plaques. This may result in a burst of inflammatory products with tissue
      degrading and vasoactive properties and, hence, could initiate or accelerate the
      onset of an acute coronary event.

PMID- 9764053
TI  - Histological patterns of atherosclerotic plaques in unstable angina patients vary
      according to clinical presentation.
AB  - BACKGROUND: Unstable angina is a heterogeneous clinical syndrome. The diverse
      clinical presentations of unstable angina may reflect different pathogenic
      mechanisms within the plaque. OBJECTIVE: To investigate the cellular constituents
      of culprit coronary atheromatous plaques in patients with stable angina pectoris
      and patients with diverse clinical presentations of unstable angina. METHODS: 48
      patients who underwent coronary atherectomy for management of ischaemic heart
      disease: 23 had stable angina and 25 had unstable angina. Of the latter, 11
      patients were classified as Braunwald's IIB and 14 as Braunwald's IIIB unstable
      angina. The presence of thrombus, cholesterol clefts, and smooth muscle cell
      proliferation was assessed in atherectomy samples using standard histological
      techniques. Monoclonal antibodies were used to identify smooth muscle cells and
      macrophages within atherosclerotic plaque fragments. RESULTS: Fresh thrombus was
      more frequently found in patients with Braunwald's IIIB unstable angina (64%)
      than in patients with stable angina (22%) or IIB unstable angina (27%) (p <
      0.0006). A pattern of smooth muscle cell proliferation ("accelerated progression
      pattern") was observed which was also associated with coronary thrombus. This
      pattern was present in 30% of patients with stable angina, 64% of patients with
      IIIB unstable angina, and in all patients (100%) with IIB unstable angina.
      Atherosclerotic plaques with thrombus, cholesterol clefts, and macrophages were
      more common in patients with unstable angina than in stable angina patients.
      CONCLUSION: The presence of a specific smooth muscle cell proliferation
      (accelerated progression) pattern in patients with unstable angina, particularly
      in those with Braunwald's IIB unstable angina, suggests that episodic plaque
      disruption and subsequent healing may be an important mechanism underlying angina
      symptoms in these patients.

PMID- 9764054
TI  - Can C reactive protein or troponins T and I predict outcome in patients with
      intractable unstable angina?
AB  - OBJECTIVE: To determine whether a single blood test for the measurement of C
      reactive protein, or troponin I or T concentrations could be used to stratify
      patients with intractable unstable angina awaiting transfer for coronary
      angiography by correlating these values with coronary anatomy and transient
      myocardial ischaemia. DESIGN: Prospective study. SETTING: Tertiary cardiac unit.
      PATIENTS: All patients admitted to their local hospital with ischaemic chest
      pain, uncontrolled by medical treatment, in whom acute myocardial infarction had
      been excluded by serial measurement of creatine kinase and lack of Q waves on
      ECG. INTERVENTION: Coronary angiography and ST segment monitoring for 24 hours.
      MAIN OUTCOME MEASURES: Concentrations of C reactive protein, troponins T and I,
      coronary anatomy, presence of transient myocardial ischaemia. RESULTS: Median C
      reactive protein, troponin I, and troponin T concentrations were 17.1 mg/dl (4.8
      to 203.9), 0.05 microgram/l (0 to 7.8), and 0.0 microgram/l (0 to 2.51),
      respectively. Seven patients (10%) had normal coronaries and 14, 20, and 31 had
      one, two, or three vessel coronary disease, respectively. Nineteen (26%) had
      transient myocardial ischaemia, 33 (46%) had complex lesion morphology, and six
      (8%) had intracoronary thrombus. Of the three markers, troponin T alone was
      higher in patients with multivessel disease (p < 0.05) and in those with
      transient myocardial ischaemia (p < 0.05), but there was no significant relation
      between C reactive protein, troponin T or I and lesion morphology or thrombus.
      CONCLUSIONS: In patients transferred to a tertiary centre with intractable chest
      pain, C reactive protein and troponin I are not predictive of transient
      myocardial ischaemia or lesion morphology, both of which are surrogate markers of
      outcome. Troponin T is, however, raised in patients with multivessel disease or
      transient myocardial ischaemia. These serum protein assays cannot be used to
      stratify the risk of patients with unstable angina who are awaiting transfer to
      the tertiary centre.

PMID- 9764055
TI  - Relation between the kinetics of thallium-201 in myocardial scintigraphy and
      myocardial metabolism in patients with acute myocardial infarction.
AB  - OBJECTIVE: To investigate the relations between myocardial metabolism and the
      kinetics of thallium-201 in myocardial scintigraphy. METHODS: 46 patients within
      six weeks after the onset of acute myocardial infarction underwent resting
      myocardial dual isotope, single acquisition, single photon emission computed
      tomography (SPECT) using radioiodinated 15-iodophenyl 3-methyl pentadecaenoic
      acid (BMIPP) and thallium-201, exercise thallium-201 SPECT, and positron emission
      tomography (PET) using nitrogen-13 ammonia (NH3) and [F18]fluorodeoxyglucose
      (FDG) under fasting conditions. The left ventricle was divided into nine
      segments, and the severity of defects was assessed visually. RESULTS: In the
      resting SPECT, less BMIPP uptake than thallium-201 uptake was observed in all of
      40 segments with reverse redistribution of thallium-201, and in 21 of 88 segments
      with a fixed defect of thallium-201 (p < 0.0001); and more FDG uptake than NH3
      uptake (NH3-FDG mismatch) was observed in 35 of 40 segments with reverse
      redistribution and in 38 of 88 segments with fixed defect (p < 0.0001). Less
      BMIPP uptake in the resting SPECT was observed in 49 of 54 segments with slow
      stress redistribution in exercise SPECT, and in nine of 17 segments with rapid
      stress redistribution (p < 0.0005); NH3-FDG mismatch was observed in 42 of 54
      segments with slow stress redistribution and in five of 17 segments with rapid
      stress redistribution (p < 0.0005). CONCLUSIONS: Thallium-201 myocardial
      scintigraphy provides information about not only myocardial perfusion and
      viability but also about myocardial metabolism in patients with acute myocardial
      infarction.

PMID- 9764056
TI  - Low molecular weight heparin as an adjunct to thrombolysis for acute myocardial
      infarction: the FATIMA study. Fraxiparin Anticoagulant Therapy in Myocardial
      Infarction Study Amsterdam (FATIMA) Study Group.
AB  - OBJECTIVE: To investigate the feasibility of fixed dose, weight adjusted
      subcutaneous low molecular weight heparin (LMWH), with monitoring of anti-Xa
      levels and assessment of coronary patency rates after three to five days, thereby
      giving an initial indication of its safety and efficacy. DESIGN: In 30 patients
      with acute myocardial infarction, LMWH (nadroparine) was given as a body weight
      adjusted intravenous bolus with thrombolysis (rt-PA infusion) and in weight
      adjusted subcutaneous doses at six hours, and every 12 hours thereafter for 72
      hours. The target range was defined prospectively as 0.35-0.70 anti-factor Xa
      activity (aXa) units. The aXa level was measured every six hours. Coronary
      angiography was performed in all patients within five days after the start of
      thrombolytic treatment to determine patency (TIMI 2 and 3 flow) of the infarct
      related artery. RESULTS: The mean (SEM) aXa level over 72 hours was 0.52 (0.08)
      U/ml; from 12 hours onwards 88% of all aXa measurements were within the target
      range. At angiography, a patent infarct related artery was present in 24 of the
      30 patients. No major bleeding complications occurred, though minor bleeding
      complications were observed in two patients. CONCLUSIONS: This small study
      indicates that LMWH is feasible as an adjunct to thrombolysis in patients with
      acute myocardial infarction. The aXa levels were within the target range and
      patency rates at three to five days were around 80%, with no major bleeding
      complications.

PMID- 9764057
TI  - Coronary event and case fatality rates in an English population: results of the
      Oxford myocardial infarction incidence study. The Oxford Myocardial Infarction
      Incidence Study Group.
AB  - OBJECTIVES: To determine coronary event and case fatality rates in an English
      population aged less than 80 years in Oxfordshire, and to compare these rates
      with those reported by the UK monitoring trends and determinants of
      cardiovascular disease (MONICA) centres in Scotland and Northern Ireland and
      those ascertained in Oxfordshire in 1966-67. DESIGN: A population wide
      surveillance study conducted in 1994-95 using prospective and retrospective case
      ascertainment. SETTING: A resident population in Oxfordshire of 568,800.
      SUBJECTS: Patients with suspected myocardial infarction or coronary death.
      OUTCOME MEASURES: A diagnosis of definite or possible myocardial infarction or
      coronary death using WHO MONICA diagnostic criteria based on symptoms,
      electrocardiograms, cardiac enzymes, necropsy findings, and past medical history.
      RESULTS: The annual rate for a first or recurrent coronary event per 100,000
      population aged less than 65 years in 1994-95 was 273 for men and 66 for women
      after age adjustment to a standard world population. Rates in the age group 65-79
      years were 1350 for men and 677 for women. Between 1966-67 and 1994-95, the age
      standardised event rate in the age group 30-69 years decreased significantly by
      33% (95% confidence interval (CI) 44 to 21) in men, and there was a non
      significant reduction of 8% (95% CI -33 to 17) in women. The age standardised 28
      day case fatality rates also decreased significantly by 28% (95% CI 41 to 15) in
      men and by 32% (95% CI 55 to 9) in women. CONCLUSIONS: The coronary event rate in
      Oxfordshire was much lower than rates reported by MONICA centres in Glasgow and
      Belfast, and similar to rates reported by MONICA centres in France and northern
      Italy. The substantially lower event rate accounts for lower coronary heart
      disease mortality in Oxfordshire than in Scotland and Northern Ireland. The
      reduced coronary mortality in this region is attributable to declines in coronary
      event and case fatality rates.

PMID- 9764058
TI  - Beta adrenergic blockers lower renin in patients treated with ACE inhibitors and
      diuretics.
AB  - OBJECTIVE: To examine the effect of concomitant intake of beta blockers with
      angiotensin converting enzyme (ACE) inhibitors, diuretics, or both on plasma
      renin concentrations in a population based sample (MONICA survey, Augsburg,
      Germany). SUBJECT AND METHODS: 728 individuals were studied, of whom 171 were
      treated using monotherapy (ACE inhibitor (n = 21), diuretic (n = 10), or beta
      blocker (n = 72)), or combination treatment (ACE inhibitor + diuretic (n = 32),
      ACE inhibitor + beta blocker (n = 7), diuretic + beta blocker (n = 22), ACE
      inhibitor + diuretic + beta blocker (n = 7)). The remaining 557 individuals were
      untreated. Indications for treatment were hypertension (75%), coronary artery
      disease with (12%) or without (3%) hypertension, or unknown (10%). RESULTS: Mean
      (SEM) renin concentrations in individuals treated with an ACE inhibitor (41 (8)
      mU/l), a diuretic (41 (10) mU/l), or the combination of an ACE inhibitor and a
      diuretic (54 (10) mU/l) were raised compared with untreated individuals (17 (1)
      mU/l; p < 0.05 each). Monotherapy with a beta blocker, however, decreased mean
      renin concentrations (12 (1) mU/l; p < 0.01 v untreated). Renin concentrations in
      individuals taking a beta blocker with either an ACE inhibitor (21 (8) mU/l), or
      a diuretic (22 (4) mU/l), or with both an ACE inhibitor and a diuretic (21 (7)
      mU/L), were significantly lower compared with renin concentrations in groups not
      receiving beta blocker treatment (p < 0.05 each). CONCLUSION: These data suggest
      that the upregulation of renin by treatment with ACE inhibitors, diuretics, or
      both can be largely prevented by concomitant beta blocker treatment.

PMID- 9764059
TI  - Transcatheter coil occlusion of residual interatrial communications after Fontan
      procedure.
AB  - OBJECTIVE: To assess the use of detachable coils as an alternative method to
      occlude interatrial communications after Fontan operations. DESIGN: Descriptive
      clinical study of selected patients after Fontan operation with interatrial
      communications inappropriate for transcatheter umbrella occlusion. SETTING:
      Tertiary paediatric cardiac referral centre. PATIENTS: Seven patients after
      Fontan operation with residual interatrial communications of various types
      producing a right to left shunt. INTERVENTIONS: Transcatheter placement of
      detachable coils with a diameter of 3 or 5 mm within the interatrial
      communication. RESULTS: A total of 14 coils were successfully placed within
      persistent patent fenestrations of the interatrial baffle, residual leaks at the
      suture line between the patch material and the right atrial wall, and unusual
      venous interatrial communications. The mean (SD) aortic oxygen saturation
      increased from 88 (1.1)% (range 86-89%) to 92 (1.3)% (range, 89-93%; p < 0.001)
      and the mean (SD) right atrial pressure rose from 9.7 (2) mm Hg (range, 6-11) to
      10.6 (2.4) mm Hg (range, 6-13; p < 0.05) after coil implantation. In five
      patients, complete obliteration of the interatrial shunt was shown by angiography
      after coil implantation. At a mean (SD) follow up of 10 (4) months (range, 3-15)
      a residual interatrial shunt was detected by Doppler colour echocardiography in
      only one patient, and oxygen saturations ranged from 90% to 95% (mean, 92%).
      There were no late coil embolisations, thromboembolic events, or haemolysis in
      any patient. CONCLUSIONS: Detachable coils can be used successfully to occlude
      residual interatrial communications after the Fontan procedure. In selected
      cases, in whom intended transcatheter umbrella occlusion of residual interatrial
      leaks is not possible, the use of detachable coils might offer a safe alternative
      method to eliminate interatrial right to left shunting after the Fontan
      procedure.

PMID- 9764060
TI  - Extending the limits of transcatheter closure of atrial septal defects with the
      double umbrella device (CardioSEAL).
AB  - OBJECTIVE: To report initial findings from a selected group of patients with
      morphological variations of the atrial septal defect who underwent transcatheter
      closure with a second generation redesigned double umbrella device. PATIENTS: Two
      patients with abnormal location of the oval fossa and partial deficiency of the
      septal rim, three patients with multiple defects, and two patients with a
      multiperforated aneurysm of the interatrial septum (age range, 3.6-25.5 years).
      METHODS: Defects were closed with the double umbrella device (CardioSEAL)
      consisting of two sets of flexible arms (with central and two mid-arm hinges)
      covered with sewn Dacron patches. The implantation procedure was monitored by
      transoesophageal echocardiography. RESULTS: The diameter of the defect measured
      during transoesophageal echocardiography ranged from 7-18 mm and the balloon
      stretched diameter ranged from 13-21 mm. The size of the devices varied from 28
      33 mm and the ratio of device size to defect size varied from 1.6-2.1. Two
      devices (23 and 28 mm) were chosen in a patient with two separated defects. No
      complications or serious arrhythmias were observed during implantation or follow
      up (median, 1.8 months). Residual shunting was trivial in three patients and mild
      in one patient (inferiorly located additional defect). CONCLUSIONS: To extend the
      selection critera of an isolated central interatrial defect for transcatheter
      closure, some modifications of the implantation technique are needed. Using the
      redesigned double umbrella device, effective closure in patients with multiple or
      irregularly shaped atrial septal defects was achieved, indicating a broadening of
      the spectrum of transcatheter closure.

PMID- 9764061
TI  - Right sided intracardiac thrombus.

PMID- 9764062
TI  - Cardiopulmonary responses to exercise in patients with hypertrophic
      cardiomyopathy.
AB  - OBJECTIVE: To examine the submaximal and maximal indices of the exercise response
      of patients with hypertrophic cardiomyopathy. DESIGN AND SETTING: Prospective
      examination of cardiopulmonary responses to ramp exercise test of a consecutive
      group of patients with hypertrophic cardiomyopathy attending a cardiomyopathy
      outpatient clinic. METHODS: 50 patients aged 12 to 76 years (mean (SD) 35 (14))
      with diagnosis of hypertrophic cardiomyopathy performed incremental cycle
      ergometry; 22 sedentary volunteers (seven female, 15 male) aged 14 to 58 years
      (mean (SD) 31 (12)) served as controls. Respiratory gas was continuously sampled
      from the mouth-piece, and its concentration profile phase aligned to the respired
      air flow signals. Following analogue to digital conversion, gas exchange
      variables were computed breath by breath and the data were averaged every 30
      seconds for graphic display. A 12 lead ECG was monitored continuously and
      recorded every three minutes during the exercise. RESULTS: Both the peak oxygen
      uptake attained on the test (VO2 peak) and anaerobic threshold were reduced in
      patients with hypertrophic cardiomyopathy compared with the control group (p <
      0.0001). In 29 patients (59%) the VO2 peak was less than 60% and only two
      patients achieved a peak above 80% of their predicted values. The anaerobic
      threshold was below 60% of the predicted value in 31 patients and above 80% in
      only three patients. The slope of oxygen uptake/work rate relation (delta
      VO2/delta WR) was decreased in 16 patients (32%). The maximum oxygen pulse
      (VO2/HR) was reduced as a percentage of the predicted value, and became flat at
      high work rates in 32 patients. There was a significant correlation between
      anaerobic threshold and VO2 peak (p < 0.0001), work efficiency (p < 0.0001), and
      maximum oxygen pulse (p < 0.0001). The slope of change in ventilation against
      change in carbon dioxide output (delta VE/delta VCO2) for the subanaerobic
      threshold range was increased in 36 patients (72%) and was inversely correlated
      with anaerobic threshold (p < 0.0002). CONCLUSIONS: There were severe
      abnormalities in maximal and submaximal indices of pulmonary gas exchange in a
      cohort of hypertrophic cardiomyopathy patients attending a referral
      cardiovascular clinic. The pattern of the abnormalities suggests that a reduced
      stroke volume response, ventilation/perfusion mismatch, and abnormal peripheral
      oxygen utilisation are the possible mechanisms of exercise intolerance.

PMID- 9764063
TI  - Potential impact of antiarrhythmic drugs versus implantable defibrillators on the
      management of ventricular arrhythmias: the Midlands trial of empirical amiodarone
      versus electrophysiologically guided intervention and cardioverter implant
      registry data.
AB  - BACKGROUND: Survival was prolonged in selected patients with sustained
      ventricular arrhythmias who received implantable cardioverter defibrillators
      (ICDs) in the antiarrhythmics versus implantable defibrillators (AVID) study. The
      Midlands trial of empirical amiodarone versus electrophysiologically guided
      intervention and cardioverter implant in ventricular arrhythmias (MAVERIC)
      registry is a population based trial. OBJECTIVE: To determine the number of
      patients who satisfy the AVID criteria because of the high cost of ICDs. DESIGN:
      Observational study, based on a continuing trial. SETTING: All coronary care
      units in the Midlands region in the United Kingdom (population 9.1 million).
      PATIENTS: Patients presenting to a coronary care unit with sustained ventricular
      arrhythmias not related to an acute myocardial infarction are entered onto the
      registry. Those who consent to the MAVERIC study are randomised to receive either
      empirical amiodarone or electrophysiologically guided treatment. Demographic
      data, details of clinical presentation, and echocardiographic findings are
      collected. These data have been used to calculate the number of patients who
      satisfy the AVID criteria and would benefit from ICD implantation. The financial
      implications have been calculated for the region and nationally. RESULTS: 132
      patients were entered onto the registry during the first five months of the
      MAVERIC study; 69 patients fulfilled the AVID criteria. Extrapolation of these
      data over a 12 month period suggests implantation of at least 166 new ICDs
      (compared with 23 implants in 1996). This would increase the UK ICD implant rate
      from five to at least 18 per million of the population, costing the National
      Health Service 24.1 Pounds million per annum. CONCLUSION: Application of the AVID
      criteria in the UK will cause a great increase in the ICD implant rate, with
      serious financial implications.

PMID- 9764064
TI  - Autonomic modulation of the atrial cycle length by the head up tilt test: non
      invasive evaluation in patients with chronic atrial fibrillation.
AB  - OBJECTIVE: To determine the effects of upright posture compared with supine
      position on the dominant atrial cycle length (DACL) in patients with chronic
      atrial fibrillation. DESIGN: The power/frequency spectrum of QRST suppressed lead
      V1 ECG was studied in 14 patients in the supine position and during the head up
      tilt table test. The DACL changes were compared with changes in heart rate and
      blood pressure. RESULTS: Compared with the supine position, the upright position
      reduced the DACL from 160 to 150 ms (p < 0.01). The DACL was increased after
      returning to the supine position from the upright position, from 147 to 154 ms (p
      < 0.01). Heart rate increased from 91 beats/min in the supine position to 106 in
      the upright position (p < 0.01). There was a decrease in heart rate from 109
      beats/min in the upright position to 93 after returning to the supine position (p
      < 0.01). No significant changes were seen in systolic or diastolic blood
      pressure. There were indications of an inverse relation between DACL and heart
      rate when comparing the supine position before and after tilt with the upright
      position (p < 0.001). CONCLUSIONS: The sympathetic stimulation and vagal
      withdrawal induced by rising to upright body position are associated with a
      decrease in DACL during chronic atrial fibrillation. Thus a reflex increase in
      sympathetic discharge after induction of atrial fibrillation could favour the
      persistence of the arrhythmia.

PMID- 9764065
TI  - Dispersion of QT and QTc interval in healthy children, and effects of sinus
      arrhythmia on QT dispersion.
AB  - OBJECTIVE: To determine the normal values of QT and QTc dispersion and the
      effects of sinus arrhythmia on QT dispersion in healthy children. PATIENTS AND
      SETTING: The study was carried out in a university hospital on 372 local
      schoolchildren (200 male, 172 female), aged seven to 18 years. METHODS: The QT
      and preceding RR intervals of at least one sinus beat were measured manually in a
      range of nine to 12 leads on standard 12 lead surface ECGs. The corrected QT
      interval was computed by the method of Bazett. Dispersion of QT and QTc were
      defined as (1) the difference between the maximum and minimum QT and QTc
      intervals occurring in any of the 12 leads (QTD and QTcD), (2) the standard
      deviation of the QT and QTc interval in the measurable leads (QT-SD and QTc-SD).
      RESULTS: There was no significant difference in QT, QTc, and RR dispersion
      between girls and boys. Overall 53% of children had sinus arrhythmia. Although
      QTD and QT-SD were not affected by sinus arrhythmia, both QTcD and QTc-SD were
      significantly greater in children with sinus arrhythmia than in those without
      (QTcD: 52.9 (17.4) v 40.9 (13.1); QTc-SD: 17.5 (5.9) v 13.2 (4.0); p < 0.001).
      CONCLUSIONS: As calculation of QTc dispersion is affected by sinus arrhythmia,
      which is common in childhood, we suggest that QT dispersion should not be
      corrected for heart rate in children.

PMID- 9764066
TI  - New electrocardiographic criteria for the differentiation between
      counterclockwise and clockwise atrial flutter: correlation with
      electrophysiological study and radiofrequency catheter ablation.
AB  - OBJECTIVE: To develop new electrocardiographic (ECG) criteria for the
      differentiation between counterclockwise and clockwise atrial flutters.
      BACKGROUND: Traditionally, the ECG differentiation between counterclockwise and
      clockwise atrial flutters is based on the flutter wave polarity in the inferior
      leads. However, determination of flutter wave polarity is subjective and
      sometimes difficult, especially in flutter waves of undulating pattern. PATIENTS:
      The study comprised 37 consecutive patients with drug resistant atrial flutter;
      30 had counterclockwise and 17 had clockwise atrial flutter (10 had both forms of
      atrial flutter). The isthmus dependence was confirmed by entrainment study and
      catheter ablation. The ECG patterns of both types of atrial flutter were compared
      and the flutter wave polarity in the inferior leads was determined by four
      independent cardiologists. RESULTS: The flutter wave polarity in the inferior
      leads appeared negative in 24, positive in one, and equivocal in five of the
      counterclockwise atrial flutters; polarity appeared negative in one, positive in
      10, and equivocal in six of the clockwise atrial flutters. However, the aVF/lead
      I flutter wave amplitude ratio was > 2.5 in all counterclockwise but < 2.5 in all
      clockwise atrial flutters. The flutter wave nadirs in the inferior leads
      corresponded to the upstrokes in V1 in all counterclockwise atrial flutters, but
      corresponded to the downstrokes in V1 in all clockwise atrial flutters.
      CONCLUSIONS: The flutter wave polarity in the inferior leads does not correlate
      well with the flutter wave rotating direction. However, counterclockwise and
      clockwise atrial flutters can be differentiated by new ECG criteria with high
      accuracy.

PMID- 9764067
TI  - Spontaneously terminating ventricular fibrillation and asystole induced by silent
      ischaemia causing recurrent syncope.
AB  - A 57 year old man was admitted for investigation of recurrent syncopal attacks.
      Holter monitoring during an attack while in hospital revealed a unique sequence
      of gross ST segment elevation, ventricular tachycardia, prolonged ventricular
      fibrillation, asystole, junctional and ventricular escape rhythm, and finally
      spontaneous restoration of sinus rhythm with severe ST segment depression.
      Subsequent coronary arteriography demonstrated severe stenoses of the right
      coronary artery, prompting percutaneous transluminal angioplasty and stenting.
      The patient has had no further syncopal attacks.

PMID- 9764068
TI  - Coronary artery spasm leading to life threatening arrhythmias.
AB  - A 39 year old woman sustained life threatening arrhythmias associated with
      coronary artery spasm. On both occasions she was attending hospital outpatient
      clinics and was successfully resuscitated. Electrocardiography performed during
      further episodes of pain suggested that spasm could occur in either the right or
      left coronary artery.

PMID- 9764069
TI  - Coronary atherosclerosis within a myocardial bridge, not a benign condition.
AB  - In patients with myocardial bridging, the area within the bridge usually remains
      free from atherosclerotic disease. The case of a 47 year old man is described who
      had the rare combination of myocardial bridging with an atherosclerotic plaque
      within the area of bridging, which was detected with intravascular ultrasound but
      not with coronary angiography. The clinical history of the patient demonstrates
      that this is not a benign condition. In symptomatic patients the bridged segment
      should be screened for the presence of plaque with intracoronary ultrasound.

PMID- 9764070
TI  - Unruptured left ventricular pseudoaneurysm following myocardial infarction.
AB  - A 73 year old man developed a left ventricular pseudoaneurysm following acute
      myocardial infarction. Coronary angiography showed triple vessel disease with
      total occlusion of the right coronary artery. On left ventriculography, a
      serpentine-like pseudoaneurysm was demonstrated that originated from the
      posterobasal wall of the left ventricle and extended to the right ventricular
      free wall. He underwent coronary artery bypass surgery with no plication of the
      pseudoaneurysm. An organised thrombus was also found within the cavity of the
      pseudoaneurysm. He was doing well approximately eight months after the operation.
      The prognosis might be determined by the organised thrombus, the serpentine-like
      structure of pseudoaneurysm, the coronary revascularisation, and the vigorous
      medical management.

PMID- 9764071
TI  - Ruptured ventricular pseudoaneurysm.

PMID- 9764072
TI  - Left ventricular pseudoaneurysm in a patient with Dressler's syndrome after
      myocardial infarction.
AB  - Successful recanalisation of the left anterior descending coronary artery was
      performed in a 51 year old man who was admitted two weeks after acute anterior
      myocardial infarction. Fourteen days later, the patient developed Dressler's
      syndrome with cardiac tamponade, which was immediately punctured. Sternotomy was
      performed after two weeks because of progressive haemodynamic deterioration, and
      fibrinous masses were removed from the pericardium. The patient recovered but two
      weeks later echocardiography showed a perforation of the left ventricular free
      wall and formation of a pseudoaneurysm. Intensive monitoring showed significant
      enlargement of the pseudoaneurysm, which was subsequently resected. This case
      demonstrates that dangerous formation of a pseudoaneurysm can occur not only
      during the first days of acute myocardial infarction but also after weeks in
      patients suffering from non-infectious pericarditis caused by Dressler's
      syndrome. Although the incidence of Dressler's syndrome is declining, patients
      should be monitored carefully for several weeks, especially by echocardiography.

PMID- 9764073
TI  - Magnetic resonance images of left ventricular pseudoaneurysm.

PMID- 9764074
TI  - Coronary stenting for symptomatic myocardial bridging.

PMID- 9764075
TI  - The rise and fall of complementary medicine.

PMID- 9764076
TI  - Psychological stress and burnout in medical students: a five-year prospective
      longitudinal study.
AB  - The aim of this study was to assess psychological morbidity and symptoms of
      burnout in medical students during their undergraduate training, and to identify
      baseline factors that predict psychological morbidity in students in the final
      year of the course. It was a 5-year prospective longitudinal cohort study.
      Students were assessed in years 1, 4 and 5 of their medical undergraduate
      training by means of the GHQ-12 and the Maslach Burnout Inventory. 172 (84.3%),
      157 (77.0%) and 155 (75.9%) students out of an original group of 204 completed
      assessments in years 1, 4 and 5, respectively. 18 students were above threshold
      on the GHQ-12 on all three occasions, 25 on two occasions and 43 on one occasion;
      69 students were never a 'case'. Students who were cases on two or more occasions
      were more likely to find the medical course stressful during the first year, but
      not subsequent years. There was no significant difference between the percentages
      of men and women who scored as cases on the GHQ-12 in any of the years. The best
      predictor of psychological morbidity in the final year of the course was the GHQ
      12 score in year 1. This study suggests that a small group of students repeatedly
      experience psychological distress during their medical training.

PMID- 9764077
TI  - Electronic fetal heart rate monitoring: retrospective reflections on a twentieth
      century technology.

PMID- 9764078
TI  - Electroencephalography and video-electroencephalography in the classification of
      childhood epilepsy syndromes.

PMID- 9764079
TI  - Medical implications of controlled fasting.

PMID- 9764080
TI  - Health statistics on the World Wide Web.

PMID- 9764081
TI  - Dysmorphophobia by proxy.

PMID- 9764082
TI  - Severe rhabdomyolysis after tiger snake bite.

PMID- 9764083
TI  - Three cases of pneumomediastinum--after labour, sneezing and compressed-air
      diving.

PMID- 9764084
TI  - Psychological aspects of eye disorders.

PMID- 9764085
TI  - Dwarfism and gigantism in historical picture postcards.
AB  - A collection of 893 historical picture postcards from 1900 to 1935, depicting
      dwarfs and giants, was analysed from medical and psychosocial viewpoints. In
      conditions such as 'bird headed dwarfism', achondroplasia, cretinism, so-called
      Aztecs or pinheads, Grebe chondrodysplasia, and acromegalic gigantism, the
      disorder could be diagnosed easily. In hypopituitary dwarfism, exact diagnosis
      was more difficult because of heterogeneity. The most common conditions depicted
      were pituitary dwarfism and achondroplasia. Most of those with gigantism had
      pituitary gigantism and acromegaly. Brothers and sisters or parents and their
      children provided evidence of mendelian inheritance of some of these disorders.
      The cards suggest that being put on show provided, at least in some cases, social
      benefits.

PMID- 9764086
TI  - The lord and the lady.

PMID- 9764087
TI  - The bittersweet demise of Herod the Great.

PMID- 9764088
TI  - Eating disorders, nursing and the Allitt report.

PMID- 9764089
TI  - Origin of the myth of vampirism.

PMID- 9764090
TI  - Perianal Paget's disease.

PMID- 9764091
TI  - Myxoedema madness.

PMID- 9764092
TI  - Thyroid click.

PMID- 9764093
TI  - Early British surgical instruments.

PMID- 9764094
TI  - Tutankhamun's paternity.

PMID- 9764095
TI  - Male reproductive toxicity of lead in animals and humans. ASCLEPIOS Study Group.
AB  - OBJECTIVE: To critically review the literature on male reproductive toxicity of
      lead in animals and humans. METHODS: A systematic literature search identified a
      total of 32 experimental studies in animals and 22 epidemiological studies, one
      case report on humans and five review articles or documents. The studies were
      evaluated by paying attention mainly to sample size, study design, exposure, and
      dose characterisation, analytical method standardisation, and quality assurance.
      RESULTS: Several studies on rats and other rodents indicated that blood lead
      concentrations > 30-40 micrograms/dl were associated with impairment of
      spermatogenesis and reduced concentrations of androgens. However, other animal
      studies, mainly about histopathological, spermatozoal, and hormonal end points,
      indicated that certain species and strains were quite resistant to the
      reproductive toxicity of lead and that different testicular lead concentrations
      could account for these differences. The human studies focused mainly on semen
      quality, endocrine function, and birth rates in occupationally exposed subjects,
      and showed that exposure to concentrations of inorganic lead > 40 micrograms/dl
      in blood impaired male reproductive function by reducing sperm count, volume, and
      density, or changing sperm motility and morphology. No relevant effects were
      detected on endocrine profile. CONCLUSION: Several factors make it difficult to
      extrapolate the animal data to the human situation. The difficulties are mainly
      due to differences between species in reproductive end points and to the level of
      exposure. Concentrations of blood lead > 40 micrograms/dl seemed to be associated
      with a decrease in sperm count, volume, motility, and morphological alterations
      and a possible modest effect on endocrine profile. Dose-response relation, in
      particular at a threshold level, is poorly understood, and site, mode, or
      mechanism of action are unknown. Also, the effects were not always the same or
      associated in the same on sperm count and concentration. Some methodological
      issues and indications for future studies are discussed.

PMID- 9764096
TI  - Development and evaluation of a quality assessment instrument for occupational
      physicians.
AB  - OBJECTIVES: To develop and apply a method for assessing the quality of the
      process of occupational health care for individual patients. METHODS: The
      scientific literature was studied to develop a method to assess the quality of
      the process of occupational rehabilitation for workers with low back pain. The
      method was applied to health care and university workers with low back pain who
      were rehabilitated by their occupational physicians. RESULTS: Assessment of
      quality of care is regarded as a four step approach. Firstly, guidelines should
      be developed and implemented. Secondly, indicators for quality and criteria to
      demarcate good and deviant quality were derived from the guidelines. Thirdly, a
      method for data collection was chosen. Finally, quality was scored. For
      occupational rehabilitation, there was some deviance from the guidelines for most
      cases, especially in continuity of care with a deviant rate of 47%. Other
      indicators deviated from 1.4%-17.4%. Occupational physicians agreed on the
      relevance of the indicators and criteria, but for three indicators they evaluated
      the criteria as too rigid. They did not agree with their own performance scores
      in 66% of the deviant cases. CONCLUSION: Assessing the quality of the process of
      occupational health care with this method is an asset to present methods, but
      more specific criteria are needed for a more sensitive assessment.

PMID- 9764097
TI  - Quartz exposures and severe silicosis: a role for the hilar nodes.
AB  - BACKGROUND: Two stonemasons working together in an environment with high
      concentrations of quartz pursued very different clinical courses; one died of
      rapidly progressive silicosis and the other developed hilar adenopathy and,
      later, early massive fibrosis. The exposures to quartz of these two men were
      investigated to allow comment on the pathogenesis of severe silicosis relative to
      concentrations of dust. METHODS: Estimates of exposure were based on previously
      taken personal dust samples, detailed lifetime occupational histories, and
      semiquantitative exposure modelling. RESULTS: One of the men who died had a 30
      year exposure estimated to have averaged < 0.1 mg/m3, leading to hilar node
      fibrosis and calcification, followed by a five year exposure to about 2 mg/m3
      which proved fatal. Estimates of exposure tallied with postmortem measurement of
      lung burden, suggesting retention of all dust deposited in the lungs over his
      final period of work. The younger man, working from the start of his
      apprenticeship alongside the older one, had a six year exposure to about 1.5
      mg/m3, which caused hilar node enlargement and subsequent calcification but
      minimal lung involvement. CONCLUSIONS: Exposures to relatively low concentrations
      of quartz may be capable of causing hilar node fibrosis, impairing the clearance
      of any quartz inhaled subsequently. The findings support the concept that
      destruction of the hilar nodes by silicotic fibrosis, impairing lung clearance,
      has an important pathogenic role in the development of massive fibrosis, and in
      men subsequently exposed to very high concentrations of respirable quartz,
      rapidly progressive silicosis.

PMID- 9764098
TI  - Lung and bladder cancer in a Norwegian municipality with iron and steel producing
      industry: population based case-control studies.
AB  - OBJECTIVES: To investigate the influence of occupation on the rising incidence of
      lung and bladder cancer among men in a Norwegian municipality where an iron and
      steel plant constituted the key industry between 1955 and 1989. METHODS: Based on
      the lung cancer cases reported to the Cancer Registry of Norway from 1980 to 1992
      a population based case-control study was performed, including 86 cases and 196
      controls. Information on occupations and smoking habits was collected through
      interviews and from the personnel files from the industrial plants. A case
      control study on bladder cancer with 52 cases and 156 controls was carried out to
      cast light on the role of polycyclic aromatic hydrocarbons (PAHs). RESULTS: An
      odds ratio (OR) for lung cancer of 2.9 (95% confidence interval (95% CI) 1.2 to
      6.7) was associated with exposure to PAHs. Based on data from personnel files,
      increased risk of lung cancer (OR 2.8 95% CI 1.1 to 7.0) was associated with work
      experience in the pig iron department at the ironworks. A non-significant OR of
      1.8 was associated with exposure to asbestos. Bladder cancer was not associated
      with exposure to PAHs at the iron, steel, and coke plant, or with experience from
      any of the production departments at the plant. CONCLUSIONS: One fifth of the
      lung cancer cases were attributed to exposure to PAHs or asbestos. More than 80%
      of the cases of lung cancer were attributed to tobacco smoking. The cancer risk
      in the pig iron department may be due to a combination of exposures to PAH,
      asbestos, or dust of mixed composition.

PMID- 9764099
TI  - Occupational exposures and squamous cell carcinoma of the oral cavity, pharynx,
      larynx, and oesophagus: a case-control study in Sweden.
AB  - OBJECTIVES: This community based case-referent study was initiated to investigate
      aetiological factors for squamous cell carcinoma of the upper gastrointestinal
      tract. METHODS: The study was based on all Swedish men aged 40-79 living in two
      regions of Sweden during 1988-90. Within that base, efforts were made to identify
      all incident cases of squamous cell carcinoma of the oral cavity, oropharynx and
      hypopharynx, larynx, and oesophagus. Referents were selected as a stratified
      (age, region) random sample of the base. The response was 90% among cases and 85%
      among referents. There were 545 cases and 641 referents in the final study group.
      The study subjects were interviewed about several lifestyle factors and a life
      history of occupations and work tasks. The exposure to 17 specific agents were
      coded by an occupational hygienist. The relative risk (RR) of cancer was
      calculated by logistic regression, standardising for age, geographical region,
      and alcohol and tobacco consumption. RESULTS: Exposure to asbestos was associated
      with an increased risk of laryngeal cancer, and a dose-response relation was
      present. The RR was 1.8 (95% confidence interval (95% CI) 1.1 to 3.0) in the
      highest exposure group. More than eight years of exposure to welding fumes was
      associated with an increased risk of pharyngeal cancer (RR 2.3 (1.1 to 4.7)), and
      laryngeal cancer (RR 2.0 (1.0 to 3.7)). There were indications of a dose-response
      for duration of exposure. Associations were also found for high exposure to
      polycyclic aromatic hydrocarbons (PAHs) and oesophageal cancer, RR 1.9 (1.1 to
      3.2). Exposure to wood dust was associated with a decreased risk of cancer at the
      studied sites. CONCLUSIONS: Some of the present findings confirm known or
      suspected associations--such as asbestos and laryngeal cancer. The study
      indicates that welding may cause an increased risk of pharyngeal as well as
      laryngeal cancer. The findings corroborate an association between exposure to
      PAHs and oesophageal cancer.

PMID- 9764100
TI  - Preventive measures reduce exposure to polycyclic aromatic hydrocarbons at a
      graphite electrode plant.
AB  - OBJECTIVE: This study assessed the efficacy of preventive measures in a graphite
      electrode plant aimed at reducing occupational exposure to polycyclic aromatic
      hydrocarbons (PAHs). METHODS: Electrode workers (n = 146) answered a
      questionnaire and provided an end of shift urine sample. Urinary 1-hydroxypyrene
      (1-hpur), a biological marker of exposure to PAHs, was measured by high
      performance liquid chromatography coupled with: (a) fluorescence detection. 1
      Hydroxypyrene concentrations were compared with the concentrations measured
      before implementing the preventive measures; and (b) those of a control group of
      54 men not occupationally exposed to PAHs. RESULTS: After implementation of
      preventive measures, median concentrations 1-hpur were significantly reduced in
      some groups of workers: by -24%, -37% and -30% in workers at the green electrode
      unit, one baking impregnation unit, and the laboratory, respectively. In workers
      at a second baking impregnation unit, in end product finishing and in the power
      station 1-hpur concentrations were unchanged. Urinary 1-hp concentrations were
      still significantly higher in each group of workers than in the control group (p
      < 0.001 for any comparison). Concentrations in the workers varied with the type
      of job, the highest values being found in workers engaged in the power station,
      in the two baking impregnation units and in the green electrode unit.
      CONCLUSIONS: Implementing preventive measures significantly reduced exposure to
      PAHs at a graphite electrode plant. The reduction in median and peak
      concentrations of 1-hpur, which reflects total exposure to, and internal dose of
      PAHs, was most evident in workers employed in the units where preventive measures
      had been taken. Despite an overall reduction, further preventive measures are
      needed to minimise exposure to PAHs and consequently the risk of adverse health
      effects.

PMID- 9764101
TI  - Work stress and recovery measured by urinary catecholamines and cortisol
      excretion in long distance coach drivers.
AB  - OBJECTIVES: To evaluate coach drivers' work stress during work and in the course
      of recovery from work by measurement of urinary catecholamines and cortisol.
      METHODS: The urinary excretion rate of adrenaline, noradrenaline, and cortisol of
      10 coach drivers was studied during a long distance trip of three days and two
      consecutive days off. Each driver was asked to provide seven urine samples on the
      working days and six urine samples on the days off. The second day off was
      considered as the baseline. RESULTS: An occupationally induced disturbance of the
      circadian rhythmicity was found for adrenaline and noradrenaline but not for
      cortisol. The mean excretion rates of adrenaline on the first working day and
      most samples on all working days were higher than the baseline. For both
      adrenaline and noradrenaline the mean excretion rates on the first day off were
      lower than the baseline. For cortisol, the mean excretion rate on all working
      days was higher than the baseline. A trend towards accumulation of cortisol
      excretion from the first working day to the third working day was found. A
      backward shift in peak concentrations was found for adrenaline and noradrenaline
      on the second working day, as was a forward shift in peak concentration of
      cortisol on both days off. CONCLUSIONS: Long distance coach drivers showed
      occupationally induced reactivity in rates of urinary excretion of adrenaline,
      noradrenaline, and cortisol. After the outward journey the rates of excretion of
      catecholamines did not return to baseline values. The course of recovery in
      adrenaline excretion after the journey showed a new phenomenon, which has been
      called "fatigue debt". It is recommended that longer resting times in shuttle bus
      trips and fixed days off after these kind of trips should be planned. Extensive
      future research should be focused on the additional relations between fatigue
      debt and health complaints.

PMID- 9764102
TI  - Ergonomic stressors and upper extremity disorders in vehicle manufacturing: cross
      sectional exposure-response trends.
AB  - OBJECTIVE: To evaluate the association between upper extremity soft tissue
      disorders and exposure to preventable ergonomic stressors in vehicle
      manufacturing operations. METHODS: A cross sectional study was conducted in one
      vehicle stamping plant and one engine assembly plant. A standardised physical
      examination of the upper extremities was performed on all subjects. An
      interviewer administered questionnaire obtained data on demographics, work
      history, musculoskeletal symptoms, non-occupational covariates, and psycho
      physical (relative intensity) ratings of ergonomic stressors. The primary
      exposure score was computed by summing the responses to the psychophysical
      exposure items. Multivariate regression analysis was used to model the prevalence
      of disorders of the shoulders or upper arms, wrists or hands, and all upper
      extremity regions (each defined both by symptoms and by physical examination plus
      symptoms) as a function of exposure quartile. RESULTS: A total of 1315 workers
      (85% of the target population) was examined. The prevalence of symptom disorders
      was 22% for the wrists or hands and 15% for the shoulders or upper arms; cases
      defined on the basis of a physical examination were about 80% as frequent.
      Disorders of the upper extremities, shoulders, and wrists or hands all increased
      markedly with exposure score, after adjustment for plant, acute injury, sex, body
      mass index, systemic disease, and seniority. CONCLUSIONS: Musculoskeletal
      disorders of the upper extremities were strongly associated with exposure to
      combined ergonomic stressors. The exposure-response trend was very similar for
      symptom cases and for physical examination cases. It is important to evaluate all
      dimensions of ergonomic exposure in epidemiological studies, as exposures often
      occur in combination in actual workplaces.

PMID- 9764103
TI  - Prevalence of work related musculoskeletal disorders in active union carpenters.
AB  - OBJECTIVES: To determine the prevalence and risk factors for work related
      musculoskeletal disorders among union carpenters. METHODS: A detailed
      questionnaire on musculoskeletal symptoms and work history was administered to
      522 carpenters. The symptom questions assessed if carpenters experienced pain,
      numbness, or tingling in a particular body region. A subset of this group then
      received a physical examination of the upper extremities and knees. RESULTS: The
      study group was primarily white (94.9%) and male (97.8%) with a mean age of 42.3
      years. The highest prevalence of work related musculoskeletal disorders cases by
      carpentry specialty ranged from 20%-24% for those doing drywall or ceiling,
      finishing or framing, and the building of concrete forms. Generally, as duration
      of employment increased, the prevalence of symptoms increased. An adjusted
      logistic regression analysis showed that the group with the longest (> or = 20
      years) duration of employment in carpentry was significantly associated with work
      related musculoskeletal disorders of the shoulders (odds ratio (OR) 3.2, 95%
      confidence interval (95% CI) 1.1 to 8.9), hands or wrists (OR 3.1, 95% CI 1.1 to
      8.4), and knees (OR 3.5, 95% CI 1.3 to 9.2). Also, analyses showed that
      carpenters who reported that they had little or no influence over their work
      schedule had significant increases of work related musculoskeletal disorders of
      the shoulders, hips, and knees with ORs of 1.9 (95% CI 1.1 to 3.2), 2.9 (95% CI
      1.1 to 7.2), and 2.3 (95% CI 1.2 to 4.1), respectively. Feeling exhausted at the
      end of day was also a significant risk factor for work related musculoskeletal
      disorders of the knee (OR 1.8, 95% CI 1.1 to 3.1). Upper extremity disorders were
      the most prevalent work related musculoskeletal disorders reported among all
      carpenters. Drywall or ceiling activities involve a considerable amount of
      repetitive motion and awkward postures often with arms raised holding heavy dry
      walls in place, whereas form work is notable for extensive lumbar flexion and had
      the two highest rates of work related musculoskeletal disorders. The psychosocial
      element of job control was associated with both upper and lower extremity
      disorders. These union carpenters, who were relatively young, already were
      experiencing considerable work related physical problems. CONCLUSION: This study
      supports the need for vigilant ergonomic intervention at job sites and early
      ergonomic education as an integral part of apprenticeship school training to
      ensure that carpenters remain fit and healthy throughout their working lifetime.

PMID- 9764104
TI  - Indoor nitrogen dioxide in homes along trunk roads with heavy traffic.
AB  - OBJECTIVES: To assess the distribution of indoor nitrogen dioxide (NO2)
      concentrations in homes located in differing environments, and to investigate the
      influence of factors such as automobile exhaust on the indoor environment.
      METHODS: The concentrations of indoor NO2 over 24 hours were measured in both the
      heating and non-heating periods in homes of pupils from nine elementary schools
      in Chiba, Japan. Information on factors that could influence indoor environments
      was collected by questionnaire. RESULTS: Indoor NO2 concentrations during the
      heating period were higher in homes with unvented heaters than in homes with
      vented heaters, although the concentrations varied greatly among homes primarily
      because of the type of heating device used. During the non-heating period, indoor
      NO2 concentrations were significantly higher in homes adjacent to trunk roads
      than in homes located in other areas. Multiple regression analysis showed that
      indoor NO2 concentrations were associated with atmospheric NO2 in homes with
      vented heaters during the heating period, and in homes in areas other than on the
      roadside during the non-heating period. In areas other than the roadside,
      cigarette smoking in indoor environments also significantly contributed to indoor
      NO2. The average concentrations of indoor NO2 in the homes of pupils attending
      each school were significantly related to the atmospheric NO2 in areas other than
      the roadside. However, the relation between indoor and atmospheric NO2
      concentrations was not significant in roadside areas. CONCLUSIONS: These findings
      suggest that indoor NO2 concentrations are related to the atmospheric NO2 and
      type of heating appliances, and are also affected by automobile exhaust in homes
      located in roadside areas.

PMID- 9764105
TI  - Occupational asthma due to porcine pancreatic amylase.

PMID- 9764106
TI  - Assessment of mechanical exposure in ergonomic epidemiology.
AB  - In recent years several different methods have been developed to assess
      mechanical exposures, which are related to musculoskeletal disorders in ergonomic
      epidemiology. Each of these methods is capable of measuring one or more aspects
      of risk factors, but has drawbacks as well. Improper application of methods might
      result in biased exposure estimates, which has serious consequences for risk
      estimates arising from epidemiological studies. The aim of this paper was to
      systematically evaluate the usefulness of different measurement methods in terms
      of accuracy and applicability. Assessment of external exposure measures by
      subjective judgements (from experts or self reports from workers), observational
      methods (on site or afterwards from video recordings), and direct measurements
      methods (at work or during laboratory simulations) are discussed for each of the
      dimensions of exposure level, duration, and frequency. It is concluded that
      expert judgements and self reports give only limited insight into the occurrence
      of tasks and activities. Further information can be obtained from observations,
      which can best be combined with direct measurements of exposure to posture,
      movement, and exerted forces to achieve exposure profiles by occupational task.
      Internal exposures estimated by biomechanical modelling mostly consider the low
      back and require information on postures of the different body segments and
      exerted forces, completed with movement data in the case of dynamic models.
      Moreover, electromyography (EMG) and measurements of intra-abdominal pressure
      might be used for this purpose. Both biomechanical models and EMG are useful
      methods to assess internal exposure, but biomechanical models should not be
      restricted to the level of compressive forces on the lower back. Finally, current
      problems and future directions in measurement strategies and methods are
      discussed.

PMID- 9764108
TI  - Comprehensive evaluation of long-term trends in occupational exposure: Part 2.
      Predictive models for declining exposures.
AB  - OBJECTIVES: To explore the effects of various factors related to the industry,
      the contaminant, and the period and type of sampling on long term declining
      trends in occupational exposure. METHODS: Linear regression analyses were used to
      assess the relation between reductions in exposure and geographical location,
      industrial sector, type of contaminant, type of monitoring, carcinogenic
      classification, calendar period, duration of sampling, and number of reductions
      in the threshold limit value during the sampling period. Both univariable and
      multivariable models were applied. RESULTS: Based on univariable analyses, the
      findings suggest that exposures declined more rapidly in manufacturing than in
      mining, more rapidly for aerosol contaminants than for vapours, and more rapidly
      when biological, rather than airborne, monitoring was conducted. Exposures
      collected more recently (first year of sampling in 1972 or later) fell more
      rapidly than exposures first evaluated during earlier periods. Irrespective of
      when the data were collected, the results also suggest that the longer the
      duration of sampling the slower the rate of decline. Taken together, we found
      that characteristics related to the contaminant, the industry, the sampling
      period, and the type of sampling explained a substantial proportion of the
      variability for exposures evaluated before 1972 (R2 = 0.78) and for sites
      evaluated both before and after 1972 (R2 = 0.91), but explained essentially no
      variation for data gathered exclusively after 1972 (R2 = 0.04). CONCLUSIONS: By
      identifying factors that have affected the rates of reduction in a consistent
      fashion, the results should guide investigators in estimating historical levels
      when studies assessing exposure-response relations are carried out.

PMID- 9764107
TI  - Comprehensive evaluation of long-term trends in occupational exposure: Part 1.
      Description of the database.
AB  - OBJECTIVES: To conduct a comprehensive evaluation of long term changes in
      occupational exposure among a broad cross section of industries worldwide.
      METHODS: A review of the scientific literature identified studies that reported
      historical changes in exposure. About 700 sets of data from 119 published and
      several unpublished sources were compiled. Data were published over a 30 year
      period in 25 journals that spanned a range of disciplines. For each data set, the
      average exposure level was compiled for each period and details on the
      contaminant, the industry and location, changes in the threshold limit value
      (TLV), as well as the type of sampling method were recorded. Spearman rank
      correlation coefficients were used to identify monotonic changes in exposure over
      time and simple linear regression analyses were used to characterise trends in
      exposure. RESULTS: About 78% of the natural log transformed data showed linear
      trends towards lower exposure levels whereas 22% indicated increasing trends.
      (The Spearman rank correlation analyses produced a similar breakdown between
      exposures monotonically increasing or decreasing over time.) Although the rates
      of reduction for the data showing downward trends ranged from -1% to -62% per
      year, most exposures declined at rates between -4% and -14% per year (the
      interquartile range), with a median value of -8% per year. Exposures seemed to
      increase at rates that were slightly lower than those of exposures which have
      declined over time. Data sets that showed downward (versus upward) trends were
      influenced by several factors including type and carcinogenicity of the
      contaminant, type of monitoring, historical changes in the threshold limit values
      (TLVs), and period of sampling. CONCLUSIONS: This review supports the notion that
      occupational exposures are generally lower today than they were years or decades
      ago. However, such trends seem to have been affected by factors related to the
      contaminant, as well as to the period and type of sampling.

PMID- 9764109
TI  - Workplace risk factors for cancer in the German rubber industry: Part 1.
      Mortality from respiratory cancers.
AB  - OBJECTIVES: To determine the cancer specific mortality by work area among active
      and retired male workers in the German rubber industry. METHODS: A cohort of
      11,663 male German workers was followed up for mortality from 1 January 1981 to
      31 December 1991. Cohort members were classified as active (n = 7536) or retired
      (n = 4127) as of 1 January 1981 and had been employed for at least one year in
      one of five study plants producing tyres or technical rubber goods. Work
      histories were reconstructed with routinely documented "cost centre codes" which
      were classified into six categories: I preparation of materials; II production of
      technical rubber goods; III production of tyres; IV storage and dispatch; V
      maintenance; and VI others. Standardised mortality ratios (SMRs) adjusted for age
      and calendar year and 95% confidence intervals (95% CIs), stratified by work area
      (employment in respective work area for at least one year) and time related
      variables (year of hire, lagged years of employment in work area), were
      calculated from national reference rates. RESULTS: SMRs for laryngeal cancer were
      highest in work area I (SMR 253; 95% CI 93 to 551) and were significant among
      workers who were employed for > 10 years in this work area (SMR 330; 95% CI 107
      to 779). Increased mortality rates from lung cancer were identified in work areas
      I (SMR 162; 95% CI 129 to 202), II (SMR 134; 95% CI 109 to 163), and V (SMR 131;
      95% CI 102 to 167). Mortality from pleural cancer was increased in all six work
      areas, and significant excesses were found in work areas I (SMR 448; 95% CI 122
      to 1146), II (SMR 505; 95% CI 202 to 1040), and V (SMR 554; 95% CI 179 to 1290).
      CONCLUSION: A causal relation between the excess of pleural cancer and exposure
      to asbestos among rubber workers is plausible and likely. In this study, the
      pattern of excess of lung cancer parallels the pattern of excess of pleural
      cancer. This points to asbestos as one risk factor for the excess deaths from
      lung cancer among rubber workers. The study provides further evidence for an
      increased mortality from laryngeal cancer among workers in the rubber industry,
      particularly in work area I.

PMID- 9764110
TI  - Workplace risk factors for cancer in the German rubber industry: Part 2.
      Mortality from non-respiratory cancers.
AB  - OBJECTIVES: To determine the mortality from non-respiratory cancers by work area
      among active and retired male workers of the German rubber industry. METHODS: A
      cohort of 11,633 male German workers was followed up for mortality from 1 January
      1981 to 31 December 1991. Cohort members were active (n = 7536) or retired (n =
      4127) on 1 January 1981 and had been employed for at least one year in one of
      five study plants producing tyres or technical rubber goods. Work histories were
      reconstructed from routinely documented "cost centre codes" and classified into
      six categories: I preparation of materials; II production of technical rubber
      goods; III production of tyres; IV storage and dispatch; V general service; VI
      others. Standardised mortality ratios (SMRs) and 95% confidence intervals (95%
      CIs), controlling for age and calendar year and stratified by work area
      (employment in respective work area for at least one year) and time related
      variables (year of hire, lagged years of employment in work area) were calculated
      from national mortality rates as the reference. RESULTS: Significant increases in
      mortality were found for pharyngeal cancer in work area IV (three deaths, SMR
      486, 95% CI 101 to 1419), oesophageal cancer in work area III (11 deaths, SMR
      227, 95% CI 114 to 407), and leukaemia in work areas I (11 deaths, SMR 216; 95%
      CI 108 to 387) and II (14 deaths, SMR 187; 95% CI 102 to 213). Furthermore,
      increased SMRs were found for stomach cancer in work area I (22 deaths, SMR 134;
      95% CI 84 to 203), colon cancer in work area II (27 deaths, SMR 131, 95% CI 86 to
      191), prostatic cancer in work area V (27 deaths, SMR 152, 95% CI 99 to 221), and
      bladder cancer in work areas IV (six deaths, SMR 253; 95% CI 93 to 551) and V (12
      deaths, SMR 159, 95% CI 82 to 279). Mortality from cancer of the liver or gall
      bladder, pancreas and kidney, and from lymphomas was not substantially increased
      in any of the work areas. CONCLUSIONS: Mortality from cancer of several sites was
      associated with specific work areas. Some of these associations have been
      reported previously. Future analyses of our study will have to determine the role
      of specific exposures in the aetiology of these cancers.

PMID- 9764111
TI  - Residential wire codes: reproducibility and relation with measured magnetic
      fields.
AB  - OBJECTIVES: To investigate the reproducibility of wire codes to characterise
      residential power line configurations and to determine the extent to which wire
      codes provide a proxy measure of residential magnetic field strength in a case
      control study of childhood leukaemia conducted in nine states within the United
      States. METHODS: Misclassification of wire codes was assessed with independent
      measurements by two technicians for 187 residences. The association between
      categories of wire code and measured level of magnetic field was evaluated in 858
      residences with both a wire code measurement and a 24 hour measurement of the
      magnetic field in the bedroom. The strength of the association between category
      of wire code and risk of leukaemia was examined in two regions with different
      average levels of magnetic field in homes with high categories of wire code.
      RESULTS: The reproducibility of any of three different classifications of wire
      codes was excellent (kappa > or = 0.89). Mean and median magnetic fields, and the
      percentage of homes with high magnetic fields increased with increasing category
      for each of the wire code classification schemes. The size of the odds ratios for
      risk of leukaemia and high categories of wire code did not reflect the mean
      levels of the magnetic field in those categories in two study regions.
      CONCLUSION: Misclassification of categories of wire code is not a major source of
      bias in the study. Wire codes provide a proxy measure of exposure to residential
      magnetic fields. If magnetic fields were a risk factor for leukaemia, however,
      there would be some attenuation of risk estimates based on wire codes because of
      misclassification of exposure to magnetic fields at both extremes of the wire
      code range. The lack of an association between high categories of wire code and
      risk of leukaemia cannot be explained by a failure of the wire code
      classification schemes to estimate exposure to magnetic fields in the study area.

PMID- 9764112
TI  - Evaluating the effectiveness of gloves in reducing the hazards of hand
      transmitted vibration.
AB  - OBJECTIVES: A method of evaluating the effectiveness of gloves in reducing the
      hazards of hand-transmitted vibration is proposed. METHOD: The glove isolation
      effectiveness was calculated from: (a) the measured transmissibility of a glove,
      (b) the vibration spectrum on the handle of a specific tool (or class of tools),
      and (c) the frequency weighting indicating the degree to which different
      frequencies of vibration cause injury. With previously reported tool vibration
      spectra and glove transmissibilities (from 10-1000 Hz), the method was used to
      test 10 gloves with 20 different powered tools. RESULTS: The frequency weighting
      for hand-transmitted vibration advocated in British standard 6842 (1987) and
      international standard 5349 (1986) greatly influences the apparent isolation
      effectiveness of gloves. With the frequency weighting, the gloves had little
      effect on the transmission of vibration to the hand from most of the tools. Only
      for two or three tools (those dominated by high frequency vibration) did any
      glove provide useful attenuation. Without the frequency weighting, some gloves
      showed useful attenuation of the vibration on most powered tools. CONCLUSIONS: In
      view of the uncertain effect of the vibration frequency in the causation of
      disorders from hand-transmitted vibration, it is provisionally suggested that the
      wearing of a glove by the user of a particular vibratory tool could be encouraged
      if the glove reduces the transmission of vibration when it is evaluated without
      the frequency weighting and does not increase the vibration when it is evaluated
      with the frequency weighting. A current international standard for the
      measurement and evaluation of the vibration transmitted by gloves can classify a
      glove as an antivibration glove when it provides no useful attenuation of
      vibration, whereas a glove providing useful attenuation of vibration on a
      specific tool can fail the test.

PMID- 9764113
TI  - Decline in lung function related to exposure and selection processes among
      workers in the grain processing and animal feed industry.
AB  - OBJECTIVES: To follow up workers in the grain processing and animal feed industry
      five years after an initial survey, and to monitor exposures to organic dust and
      endotoxin and changes in prevalence of respiratory symptoms and lung function.
      METHODS: Outcome measures in the present survey were decline in lung function
      over five years, rapid annual decline in forced expiratory volume in one second
      (FEV1) above 90 ml.s-1, and loss to follow up. RESULTS: Among 140 workers
      included in the longitudinal analysis, annual decline in FEV1 and maximal mid
      expiratory flow (MMEF) were significantly related to occupational exposure to
      dust and endotoxin in the grain processing and animal feed industry. Assuming a
      cumulative exposure over a working life of 40 years with an exposure of 5 mg.m-3,
      the estimated effect on the FEV1 would be a decline of 157 ml.s-1 (95% CI 13 to
      300)--that is, about 4% of the group mean FEV1 and 473 ml.s-1 (95% CI 127 to 800)
      of the MMEF (about 12%). Workers with a dust exposure > 4 mg.m-3 or endotoxin
      concentrations > 20 ng.m-3 at the 1986-8 survey had significantly higher risk of
      rapid decline in FEV1 (odds ratio (OR) 3.3, 95% CI 1.02 to 10.3). The relations
      between occupational exposure and decline in lung function in this study
      occurred, despite the selection through the healthy worker effect that occurred
      as well. Increasing working years was related to decreasing annual decline in
      FEV1 and fewer people with rapid decline in FEV1 (OR 0.04, 95% CI 0 to 0.61 for
      over 20 v < 5 working years in the grain processing and animal feed industry).
      The presence of respiratory symptoms at baseline was a strong predictor of
      subsequent loss to follow up. Baseline lung function was not found to be
      predictive of subsequent loss to follow up. However, among workers lost to follow
      up the number of working years was more strongly negatively related to baseline
      lung function than among the workers who were studied longitudinally.
      CONCLUSIONS: The existence of the healthy worker effect implies that an exposure
      response relation in the grain processing and animal feed industry may well be
      underestimated. This should be taken into account when health based recommended
      limit values are to be developed.

PMID- 9764114
TI  - Changes in airway function and bronchial responsiveness after acute occupational
      exposure to chlorine leading to treatment in a first aid unit.
AB  - OBJECTIVES: To describe the baseline characteristics and the time course of
      changes in lung function in workers accidentally inhaling high concentrations of
      chlorine in a prospective study. METHODS: Baseline spirometry and methacholine
      challenge test were performed in a cohort of 278 workers at risk of accidental
      inhalation of chlorine. Workers in whom accidental inhalation led to intervention
      in a first aid unit were reassessed five to 25 days after the accident and
      serially thereafter when there where notable changes. RESULTS: During a four year
      follow up period, 13 workers were seen at the first aid unit after a symptomatic
      accidental inhalation. Three of them experienced notable functional changes: one
      worker experienced a 10% fall in forced expiratory volume in one second (FEV1),
      and the other two had a notable fall in the concentration of methacholine that
      caused a 20% fall in FEV1 (PC20). Two workers were smokers and one had a personal
      history of atopy. Baseline assessment was within the normal range in these three
      workers. Recovery was complete three months after the accidental inhalation.
      CONCLUSION: Transient but notable decreases in airway function or increases in
      bronchial responsiveness can occur after an accidental inhalation of high
      concentrations of chlorine in workers at risk.

PMID- 9764115
TI  - Acute myeloid and monocytic leukaemia and benzene exposure in petroleum
      distribution workers in the United Kingdom.

PMID- 9764117
TI  - Dynamite plunger plots should not be used.

PMID- 9764116
TI  - Occupational asthma due to amylase.

PMID- 9764118
TI  - Preventive strategies in early psychosis: verging on reality.

PMID- 9764119
TI  - Early detection and intervention of schizophrenia: rationale and research.
AB  - BACKGROUND: The primary rationale for early detection and intervention in
      schizophrenia is the disorder's severity, chronicity and treatment resistance.
      This suggests that researchers pay closer attention to schizophrenia's premorbid
      and onset phases, when the vulnerability to psychosis becomes expressed and the
      neurobiological deficit processes driving symptom formation appear to be the most
      active. METHOD: We review the evidence that brain plasticity may be retained or
      reversed despite deficit processes. RESULTS: The data are preliminary but
      suggestive enough to warrant further research. CONCLUSIONS: Overall, we need to
      focus on the early course of schizophrenia, detecting cases early at onset or in
      the prodrome, testing whether this enhances treatment response and prognosis, and
      predicting at-risk cases early in the prodromal phase. Designs to address these
      questions are presented, and relevant issues are discussed.

PMID- 9764120
TI  - School teacher ratings predictive of psychiatric outcome 25 years later.
AB  - BACKGROUND: The current study examines teacher ratings as a tool for identifying
      students at risk of developing psychosis. Follow-up and follow-back studies have
      shown that teachers are capable of identifying individuals who later develop
      serious mental illness. METHOD: We examine the long-term outcomes for individuals
      at genetic risk who were identified as showing markedly deviant behaviour and
      those identified who did not show markedly deviant behaviour. RESULTS: Teachers
      were able to correctly anticipate 35% of students who developed schizophrenia.
      Furthermore, those identified as showing markedly deviant behaviour had poorer
      clinical and psychiatric outcomes 10 and 25 years later than those identified as
      not behaving with marked deviance. Their ratings also differentiated, within the
      group of people with schizophrenia, which individuals would show evidence of
      poorer functioning 25 years later. These results were replicated in a group of
      students not at genetic risk of schizophrenia. Within this low-risk group,
      teachers were able to predict which students would develop psychotic disorders.
      CONCLUSIONS: Teacher ratings were particularly useful in predicting clinical and
      psychiatric outcomes 10 and 25 years later. The applicability of these findings
      in early intervention and treatment research is discussed.

PMID- 9764121
TI  - Prediction of psychosis. A step towards indicated prevention of schizophrenia.
AB  - BACKGROUND: The identification of people at high risk of becoming psychotic
      within the near future creates opportunities for early intervention prior to the
      onset of psychosis to prevent or minimise later ill-health. The present study
      combines current knowledge about risk factors for schizophrenia with our
      knowledge of psychotic prodromes in an attempt to identify a group particularly
      vulnerable to impending psychosis. We wanted to identify people with high
      likelihood of transition to psychosis within a follow-up period of 12 months, and
      to determine the rate of transition to psychosis in this group. METHOD: Various
      state and trait risk factors for psychosis were used alone and in combination to
      operationally define a putatively high-risk group. Operationalised criteria for
      onset of psychosis were established. The individuals were assessed monthly on
      measures of psychopathology for six months. RESULTS: Eight out of 20 people made
      the transition to frank psychosis within a six-month follow-up period. Follow-up
      of this group is still in progress, and the 12 month transition rate might prove
      to be higher still. CONCLUSIONS: We have demonstrated that it is possible to
      identify individuals with a high likelihood of onset of psychosis within a brief
      follow-up period. This lays the foundation for early treatment in an attempt to
      prevent, delay or minimise the severity of first onset of schizophrenia.

PMID- 9764122
TI  - Understanding the topography of the early psychosis pathways. An opportunity to
      reduce delays in treatment.
AB  - BACKGROUND: This study aims to gain an understanding of treatment delays and
      their nature in initial psychotic episodes. We investigated to whom people turn
      for help, how long that approach takes and subsequent delays in commencing
      treatment. METHOD: Qualitative and quantitative methods were combined with
      interviews of 62 people suffering from first-episode psychoses, aged 16-30 years,
      who had recently accessed a specialist mental health service in Melbourne,
      Australia. A modified version of the World Health Organization Encounter Form was
      analysed in conjunction with other data. RESULTS: Pathways to care and the ways
      in which they were experienced were highly variable, with 50% of people
      experiencing psychotic symptoms before approaching any service. The general
      practitioner played a key role with 50% of people having had GP contact at some
      point prior to commencing effective treatment. Where an individual's own efforts
      to seek early help failed, the role of relatives and others was subsequently
      vital. CONCLUSIONS: Opportunities exist for shortening delays through targeted
      health promotion activities and professional training. The need is indicated for
      a multi-layered or topographical strategy to identify and minimise critical
      barriers on the route to early intervention. Refinement of interview techniques
      and instruments of measurement are needed to enhance the explanatory power of
      data collected.

PMID- 9764123
TI  - Hillside study of risk and early detection in schizophrenia.
AB  - BACKGROUND: The Hillside Study of Risk and Early Detection in Schizophrenia is a
      prospective study of young probands (ages 14-28) and their at-risk siblings (ages
      14-24). A major goal is the identification of early predictors of illness that
      will facilitate intervention. The project design and pilot study are discussed.
      METHOD: Fifteen adolescents were compared to 14 typical age-of-onset adults, all
      undergoing their first hospitalisation for schizophrenia. RESULTS: There were no
      differences between adolescents and adults on any of the measures administered
      (i.e. attention, eye tracking, neurocognitive or clinical). In addition, for the
      sample overall, no association was found between neurocognitive functions and
      clinical state, either at admission or after treatment. CONCLUSIONS: Individuals
      with adolescent onset of schizophrenia are considered to be representative of
      schizophrenia in general. Furthermore, neurocognitive deficits and clinical
      symptoms are concluded to be two independent classes of risk indicators.

PMID- 9764124
TI  - Early intervention for schizophrenic disorders. Implementing optimal treatment
      strategies in routine clinical services. OTP Collaborative Group.
AB  - BACKGROUND: Early detection and intervention in schizophrenic disorders is an
      important challenge for psychiatry. METHOD: Review of literature on effective
      biomedical and psychosocial intervention strategies. RESULTS: Comprehensive
      programmes of drug and psychosocial interventions with adults who show early
      signs and symptoms of schizophrenic disorders may contribute to a lower incidence
      and prevalence of major episodes of schizophrenia. These programmes combine early
      detection of psychotic features by primary care services, with close liaison with
      mental health professionals. Long-term monitoring of signs of recurrence, with
      further intervention, appears essential to maintain these benefits. CONCLUSIONS:
      Field trials demonstrate that effective early treatment strategies can be
      routinely applied in clinical practice.

PMID- 9764125
TI  - Home-oriented management programme for people with early psychosis.
AB  - BACKGROUND: The HOMES (Home-Oriented Management of Early Psychosis) programme is
      a new home-based management programme for people presenting for the first time
      with psychotic illnesses. The present paper aims to present preliminary data as
      to the efficacy of this programme and factors identified as being associated with
      successful prevention of hospital admission. METHOD: The programme applied to all
      the people presenting to the Dandenong Hospital Department of Psychiatry with
      first-episode psychosis who are considered suitable at first assessment for home
      based management. A programme description is included in the paper. Prospective
      evaluation data on the first 31 people managed within the programme is presented.
      RESULTS: Twenty-two out of 31 people were managed without the necessity for
      hospital admission. Illness severity was not related to the ability to manage
      this group of people outside of hospital. The level of social support and
      duration of untreated psychosis prior to treatment, may be most closely related
      to home-based treatment success. CONCLUSIONS: Home-based management of people
      with first-episode psychosis is feasible and offers a viable alternative to
      admission for this group. Home-based treatment is dependent on the degree of
      social support but is independent of the degree of illness severity.

PMID- 9764126
TI  - First-episode schizophrenia with long duration of untreated psychosis. Pathways
      to care.
AB  - BACKGROUND: The early course of illness in first-episode schizophrenia was
      examined with special emphasis on the duration of untreated psychosis and
      pathways to care. METHOD: The consecutively admitted individuals (n = 34) were
      assessed on premorbid functioning, duration of untreated psychosis, global
      functioning, symptoms and social network. To clarify the obstacles for receiving
      earlier treatment, 17 case histories with long duration of untreated psychosis
      were intensively studied. RESULTS: The duration of untreated psychosis was on
      average very long (130 weeks), the median value was 54 weeks. The long duration
      of untreated psychosis group (> 54 weeks) had greater deterioration in the
      premorbid phase, a weaker social network and were more withdrawn than the short
      duration of untreated psychosis group (< 54 weeks). The main obstacles for
      receiving treatment were withdrawal and poor social network. CONCLUSIONS: In
      order to identify people earlier, a system of detection must be mobile, easily
      accessible and attentive to early symptoms of psychosis. It seems to be important
      to educate the social network related to the individual about the importance of
      early treatment.

PMID- 9764127
TI  - Early intervention in psychosis. The critical period hypothesis.
AB  - BACKGROUND: We consider the evidence for the proposition that the early phase of
      psychosis (including the period of untreated psychosis) is a critical period in
      which (a) long-term outcome is predictable, and (b) biological, psychological and
      psychosocial influences are developing and show maximum plasticity. METHOD: First
      episode prospective studies, predictors of outcome and the genesis of patients'
      key appraisals of their psychosis are reviewed. RESULTS: The data support the
      notion of the 'plateau effect', first coined by Tom McGlashan, which suggested
      that where deterioration occurs, it does so aggressively in the first 2-3 years;
      and that critical psychosocial influences, including family and psychological
      reactions to psychosis and psychiatric services, develop during this period.
      CONCLUSIONS: The early phase of psychosis presents important opportunities for
      secondary prevention. We outline a prototype of intervention appropriate to the
      critical period. The data challenge the widely held assumption that first-episode
      psychosis is a benign illness posing little risk.

PMID- 9764128
TI  - Research and treatment strategies in first-episode psychoses. The Pittsburgh
      experience.
AB  - BACKGROUND: Studies of first-episode patients allow investigation of the
      biological basis of psychotic disorders without the potential confounds of prior
      treatment and illness chronicity. Prospective studies of this population can
      clarify the impact of illness course and treatment on neurobiology. METHOD: We
      summarise preliminary findings from our ongoing magnetic resonance imaging and
      spectroscopy studies of first-episode schizophrenia patients being conducted
      prospectively from index evaluations through a period of two years; during this
      period, patients were treated with either a conventional antipsychotic such as
      haloperidol, or the atypical risperidone. RESULTS: Baseline neurobiological
      evaluations in first-episode schizophrenia patients have revealed evidence for
      structural and functional brain abnormalities consistent with a
      neurodevelopmental model of this illness. Our preliminary data support the value
      of risperidone as an antipsychotic drug of first choice among patients with early
      schizophrenic illness. CONCLUSIONS: Focused studies of first-episode patients
      have the potential to unravel pathophysiology of schizophrenic illness. Such
      knowledge is critical for more effective early detection, intervention and even
      prevention of this enigmatic disorder.

PMID- 9764129
TI  - Pharmacotherapy of first-episode schizophrenia.
AB  - BACKGROUND: A growing interest in first-episode schizophrenia reflects the belief
      that this line of investigation will lead to further developments regarding
      schizophrenia's aetiology, course and outcome. METHOD: Evidence from more recent
      clinical trials involving first-episode schizophrenia is integrated with
      neuroimaging data, specifically positron emission tomography, to provide
      direction regarding pharmacotherapy. RESULTS: Individuals with a first episode of
      schizophrenia appear particularly responsive to pharmacotherapy, as well as quite
      sensitive to side-effects. At the same time, current clinical and receptor
      binding data support the efficacy of low-dose neuroleptic treatment. CONCLUSIONS:
      Early and effective treatment of schizophrenia has been associated with better
      long-term outcome. Low-dose neuroleptic therapy is an effective treatment
      strategy and the diminished risk of side-effects with this approach may further
      enhance compliance and outcome.

PMID- 9764130
TI  - Analysis of the initial treatment phase in first-episode psychosis.
AB  - BACKGROUND: The Early Psychosis Prevention and Intervention Centre (EPPIC)
      commenced operation in Melbourne, Australia, in 1992. It offers a model for
      management of first-episode psychosis, utilising principles of early detection,
      low-dose medication and comprehensive psychosocial interventions within the least
      restrictive setting. METHOD: Data were examined from the first three months of
      treatment for all consecutive people with first-episode psychosis (n = 231)
      accepted in the programme in 1995-1996. A subsample of patients (n = 120) was
      assessed comparing clinical ratings with variables of gender, diagnosis,
      hospitalisation, and medication. RESULTS: Hospitalisations were brief, and
      avoided for a third of the people. Low-dose antipsychotic medication was
      maintained in both in-patient and community settings. Those people with manic
      psychosis were more likely to be hospitalised. Hospitalised people received
      higher antipsychotic dosages, and had a greater rate of reduction in Brief
      Psychiatric Rating Scale psychotic subscale scores at three months follow-up.
      Eighty per cent of a representative subsample had responded to treatment and 63%
      were in remission by the end of the three months. CONCLUSION: This naturalistic
      study suggests that the feasibility of implementing the EPPIC model in a range of
      clinical settings is promising and applicable in practice.

PMID- 9764131
TI  - First-episode schizophrenia. Early intervention and medication discontinuation in
      the context of course and treatment.
AB  - BACKGROUND: The concept that early intervention with antipsychotic medications
      improves the long-term course of schizophrenia is discussed. METHOD: This report
      reviews the literature concerning early intervention with antipsychotic
      medications for people with first episodes, and how it affects long-term
      morbidity. It also studies the effects of discontinuing antipsychotic medications
      on relapse for people with first episodes. RESULTS: Early intervention with
      antipsychotic medications appears to decrease the long-term morbidity of
      schizophrenia. CONCLUSIONS: Early intervention with antipsychotic medications
      should be encouraged for people experiencing their first episode of
      schizophrenia. This report proposes that studying the various phases of subject
      response to treatment can be helpful in elucidating when antipsychotic
      medications should be tapered or withdrawn.

PMID- 9764132
TI  - Early intervention, untreated psychosis and the course of early schizophrenia.
AB  - BACKGROUND: Studies have proved that early intervention can delay psychotic
      relapses, and prevent psychosocial deterioration in people with schizophrenia and
      related disorders. METHOD: Our study with young people with recent onset
      schizophrenia has shown that an intensive intervention programme had a beneficial
      effect on the occurrence of psychotic relapse and the course of psychotic
      syndromes. This effect lasted until the end of the 15-month intervention. No
      significant effect of the two different intervention conditions became apparent.
      RESULTS: The results of a follow-up study showed that this beneficial effect did
      not last. Fifteen per cent of the people had a psychotic relapse during the
      intervention, whereas 64% relapsed during follow-up. CONCLUSIONS: These results
      show that referral to other mental health agencies after intervention is not
      sufficient and that more support is required to continue disease management,
      medication compliance and stress management.

PMID- 9764133
TI  - Depression in people with first-episode schizophrenia.
AB  - BACKGROUND: Depression has been described in people presenting with first-episode
      schizophrenia, a group at high relative risk of suicide. METHOD: This was a
      longitudinal cohort study of 113 people during an acute relapse and 13 having a
      first episode. Follow-up occurred at three months and at one year. This report
      compares level of depression in the first episode and in the relapsing group.
      Levels of depression were assessed using the Calgary Depression Scale for
      Schizophrenia (CDSS). RESULTS: The median CDSS score was statistically
      significantly higher in the first-episode group both during the acute phase and
      at three month follow-up. At one year the first-episode group continued to have
      higher levels of depression than the multiple episode group. CONCLUSIONS: For
      people with a first episode of schizophrenia, depression is a major problem
      during the initial acute phase and during the first year of illness. In light of
      the high risk of suicide in this population, recognition and treatment of
      depression requires greater attention.

PMID- 9764134
TI  - Cognitively-oriented psychotherapy for early psychosis (COPE). Preliminary
      results.
AB  - BACKGROUND: The present study describes the results of the pilot testing of a
      therapy we have developed for people with first-episode psychosis. Cognitively
      oriented psychotherapy for early psychosis (COPE) is aimed at facilitating the
      adjustment of the person, and at preventing or alleviating secondary morbidity in
      the wake of the first psychotic episode. METHOD: Eighty people formed three
      groups: those who were offered and accepted COPE (COPE subjects); those who
      refused COPE (refusal subjects); and those who were offered neither COPE nor any
      other continuing treatment from our service (control subjects). The individuals
      were assessed prior to, and at the end of, COPE treatment (a 12-month period) on
      the Integration/Sealing Over, Explanatory Model, Scale for the Assessment of
      Negative Symptoms, Brief Psychiatric Rating Scale, Quality of Life, SCL-90-R, and
      Beck Depression Inventory measures. RESULTS: People who received COPE obtained
      significantly superior scores (P < 0.05) to the control group on four of the
      seven measures but only significantly out-performed the refusal group on one of
      the seven measures (P < 0.05). The COPE group performed significantly worse on
      the BDI than the refusal group (P < 0.05). Effect sizes are also provided for
      each measure. CONCLUSIONS: There seems to be a place for psychological therapy in
      this group of people but our results need to be replicated in a more definitive
      randomised controlled trial and such a study is now in progress.

PMID- 9764135
TI  - Individual cognitive-behavioural interventions in early psychosis.
AB  - BACKGROUND: Cognitive-behavioural treatments have previously been explored in the
      treatment of chronic psychotic problems, but recently, the effectiveness of these
      treatments has been investigated with regard to recent onset and acute psychosis.
      METHOD: The literature relating to cognitive-behavioural treatments in psychosis
      is explored and the application of the approach to recent onset psychosis is
      described in detail. RESULTS: There appears to be a growing body of evidence that
      the advances made in the treatment of people with chronic treatment resistant
      psychosis can be similarly applied to people with recent onset and acute
      psychosis. CONCLUSIONS: Cognitive-behavioural treatments are feasible with recent
      onset psychotic patients although further evaluation of their effectiveness is
      necessary.

PMID- 9764136
TI  - Prolonged recovery in first-episode psychosis.
AB  - BACKGROUND: Early identification and specialised treatment of individuals with
      enduring positive symptoms may assist in alleviating symptoms and has the
      potential to change the course of illness. METHOD: Prevalence and descriptive
      data on enduring positive symptoms in two first-episode samples are outlined.
      Attempts to incorporate the focus of early intervention for persisting psychosis
      into routine clinical care of individuals with first-episode psychosis are
      described. RESULTS: Of the 227 individuals with first-episode psychosis who were
      assessed using the Brief Psychiatric Rating Scale at 3/6 months and 12 months
      following initial stabilisation (from a total sample of 347), 6.6% experienced
      enduring positive symptoms at all three time points. When the analysis was
      restricted to schizophrenia, schizophreniform and schizoaffective disorders (n =
      158) the percentage increased to 8.9%. These patients had significantly longer
      mean duration of untreated psychosis prior to initiation of treatment and, at 12
      month follow-up, significantly higher depression and poorer psychosocial
      functioning. CONCLUSIONS: The association of untreated psychosis with treatment
      resistance supports the argument for early intervention as soon as possible
      following the onset of psychotic symptoms.

PMID- 9764137
TI  - Group programmes for recovery from early psychosis.
AB  - BACKGROUND: We evaluate the impact of a group-based, transitional, psychosocial
      programme, within a comprehensive service (the Early Psychosis Prevention and
      Intervention Centre, EPPIC), on recovery from first-episode psychosis. METHOD:
      Individuals using the service (and meeting study criteria) were assessed on a
      range of symptom and functioning instruments at entry, after 6 weeks and 6
      months. Participants received comprehensive case management and services
      according to their identified needs. Thirty-four people who had attended the
      group programme were compared at 6 month follow-up with 61 EPPIC patients who had
      not attended. RESULTS: The people attending the group programme had a lower level
      of premorbid adjustment than the comparison group, and a trend towards exhibiting
      a higher level of negative symptoms, prior to commencing the group programme.
      However, at 6 month follow-up, no significant differences were found between the
      groups. CONCLUSIONS: Involvement in the group programme may have had a positive
      impact on a subgroup of EPPIC subjects with poor level of premorbid adjustment,
      by providing a 'holding pattern' in the critical period following the emergence
      of first-onset psychosis, and thus prevented deterioration and the development of
      disability.

PMID- 9764138
TI  - Stress and coping in early psychosis. Role of symptoms, self-efficacy, and social
      support in coping with stress.
AB  - BACKGROUND: Although coping with stress is important in early psychosis, little
      is known about how this population copes with the range of stressors they
      encounter in their daily life. This study aims to identify how people with early
      psychosis cope with a range of stressful situations and to identify what factors
      might influence their use of coping strategies. METHOD: Participants included a
      clinical group of 50 people with early psychosis and a non-clinical group of 22
      people matched on age and gender. Data were obtained on symptomatology and social
      support for the clinical group, and stress and coping, and self-efficacy for all
      participants. RESULTS: The clinical group reported coping less well than the non
      clinical group and they most commonly used emotion-focused coping. For the
      clinical group, effective coping correlated with less severe negative symptoms,
      greater perceived self-efficacy, social support and greater use of problem
      focused coping. Self-efficacy and social support predicted increased frequency of
      the use of problem-focused coping. CONCLUSION: People with early psychosis who
      have greater feelings of self-efficacy and perceived social support, and the
      flexible use of problem-focused coping strategies, appear to be more likely to
      cope with day-to-day stressors.

PMID- 9764139
TI  - Emotional management therapy in early psychosis.
AB  - BACKGROUND: Emotional management therapy (EMT) aims to improve handling of
      emotional stress in schizophrenia. It consists of two sub-programmes: the first
      includes relaxation techniques, the second stress coping skills. METHOD: A pilot
      study of EMT in 19 patients with early psychosis produced positive results and a
      post-hoc study of 16 patients was commenced. RESULTS: EMT showed positive
      results, with chronic patients improving more than patients with early psychosis.
      CONCLUSION: EMT can be effective in early psychosis, especially for cognitive
      functioning.

PMID- 9764140
TI  - Effect of substance misuse in early psychosis.
AB  - BACKGROUND: Studies examining the temporal relationship between substance use and
      the onset of psychotic symptoms in schizophrenia are inconclusive. METHOD: Three
      groups of out-patients with schizophrenia were compared on onset of illness,
      symptoms and quality of life. Fifty-one subjects had no past or present history
      of substance misuse, 29 subjects had a history of past substance misuse occurring
      around the onset of their illness, and 33 subjects were currently misusing
      substances. RESULTS: Current substance misusers had poorer quality of life scores
      and less negative symptoms than the non-users. Those who had a past history of
      substance misuse had a significantly earlier age of onset than those with no
      substance use. CONCLUSIONS: Attention should be paid to substance misuse present
      at the first episode. Treatment for schizophrenia should begin even though a
      diagnosis of drug-induced psychosis cannot be ruled out.

PMID- 9764141
TI  - p53-dependent DNA repair and apoptosis respond differently to high- and low-dose
      ultraviolet radiation.
AB  - p53 plays an essential part in the maintenance of the cellular genetic stability
      after a DNA-damaging event such as ultraviolet (UV) radiation. Following UV
      radiation, the amount of p53 protein is elevated. The increased p53 is believed
      to induce cell cycle arrest, promote nucleotide excision repair (NER) and
      apoptosis. To study if cells respond differently to high- and low-dose UV
      radiation, we examined the DNA repair efficiency and apoptosis rate of human and
      murine fibroblasts after UV radiation. Using a host cell reactivation assay, we
      found that NER was increased after low doses but not after high doses of UV
      radiation. In contrast, apoptosis occurred only after the cells received high
      doses (over 200 J/m2), but not low doses of UVB. The induction of both NER and
      apoptosis was observed only in p53+/+ murine fibroblasts, not in p53-/- cells,
      indicating that both stress response mechanisms are dependent on wild-type p53
      function. UV radiation induced the expression of p53 protein in a dose-dependent
      manner up to 400 J/m2. In contrast, p21waf1/cip1 was induced only after low doses
      and bax only after high doses of UV radiation, supporting the roles of
      p21waf1/cip1 and bax in NER and apoptosis, respectively. Taken together, these
      results indicate that cellular stress response to UV radiation depends on UV
      dose, DNA repair after low doses and apoptosis after high doses, and that both
      mechanisms are dependent on wild-type p53 function.

PMID- 9764142
TI  - Protein kinase C isoform levels in normal and sodium dodecyl sulphate-irritated
      mouse skin.
AB  - Protein kinase C (PKC) comprises a family of related phospholipid-dependent
      serine/threonine protein kinases. PKC is important in signal transduction,
      regulating cell proliferation and differentiation. Recently, it has also been
      suggested that PKC may play a part in the pathogenesis of contact dermatitis.
      However, the expression of PKC isoforms in the skin of mice with irritant contact
      dermatitis (ICD) has not been examined. In this study, ICD was induced in mouse
      skin by applying 5%, 10% and 20% sodium dodecyl sulphate (SDS) in Finn chambers
      on the backs of mice and fixing with surgical dressings for 24 h. Depending upon
      the SDS concentration, mild to strong skin irritant reactions were observed 24 h
      after removal of the irritant patches. The intensity of the reactions increased
      with the increasing concentration of SDS. PKC isoforms alpha, beta, gamma and
      delta were all detected in normal mouse skin by Western immunoblotting. The
      specificity of the PKC isoforms detected was identified further by competitive
      Western immunoblotting. Compared with normal mouse skin treated with double
      distilled water, the levels of PKC isoforms alpha, beta, gamma and delta in the
      SDS-irritated mouse skin was decreased by 24.8-75.8%. These results suggest that,
      in SDS-ICD, mouse skin PKC isoforms alpha, beta, gamma and delta are down
      regulated. The significance of this decrease is under further investigation.

PMID- 9764143
TI  - Cyclosporin A inhibits 12-O-tetradecanoyl-phorbol-13-acetate-induced cutaneous
      inflammation in severe combined immunodeficient mice that lack functional
      lymphocytes.
AB  - A single application of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) to mouse skin
      results in an acute inflammatory response, with an influx of neutrophils and
      lymphocytes, epidermal hyperplasia and abnormal keratinocyte differentiation.
      This response is significantly inhibited by topical cyclosporin A (CyA). Although
      CyA is known to inhibit T-cell activation, the role of T cells in TPA-induced
      cutaneous inflammation is not well understood. In this study, we have used severe
      combined immunodeficient (SCID) mice, which carry a spontaneous mutation
      resulting in the absence of functional T and B lymphocytes, to examine whether
      lymphocytes are required for the TPA response in mouse skin and whether CyA
      inhibits the TPA response in SCID mice. A significant increase in epidermal and
      deep dermal inflammation was observed in both SCID and CB-17 mice 24 h after a
      single application of TPA (10 nmol) compared with vehicle (P < 0.05, n = 5-7).
      Simultaneous application of CyA (1.7 mumol) plus TPA resulted in a significant
      reduction in epidermal and deep inflammation at 24 h compared with TPA alone in
      SCID and CB-17 mice (P < 0.05, n = 7). In contrast to hairless mice, a variable
      increase in epidermal thickness was observed in both SCID and CB-17 mice after
      treatment with TPA at 24 and 72 h, which was not significantly affected by CyA.
      These data indicate that TPA-induced inflammation in mouse skin does not depend
      on lymphocytes. In addition, the inhibition of TPA-induced epidermal and deep
      dermal inflammation by CyA in SCID mouse skin suggests that CyA exerts effects on
      cutaneous inflammation in mice in the absence of functioning T cells.

PMID- 9764144
TI  - Demonstration of increased levels of type I collagen mRNA using quantitative
      polymerase chain reaction in fibrotic and granulomatous skin diseases.
AB  - Collagen changes occur in localized scleroderma, scleredema and sarcoidosis.
      Previous biochemical, immunohistochemical and in situ hybridization studies have
      revealed increased collagen synthesis in these diseases. In the present study, we
      measured by pro alpha 1 (I) collagen and beta-actin mRNA levels in skin punch
      biopsy specimens from lesional and healthy skin using a quantitative polymerase
      chain reaction (PCR). In this method, the targeted mRNA and a synthetic RNA as a
      internal standard are co-amplified together with the same primers. The amount of
      pro alpha 1 (I) collagen mRNA in cutaneous sarcoidosis lesions was found to be
      increased about two- to threefold compared with the values obtained for the
      healthy skin of the same two patients. In lesional skin of three patients with
      localized scleroderma the number of pro alpha 1 (I) collagen molecules was
      increased about two-fold. The beta-actin mRNA values were at the same level in
      the affected and unaffected skin of all the patients studied. In conclusion, a
      marked increase in type I collagen gene expression was seen in localized
      scleroderma and scleredema, leading to fibrosis of the skin, and in a
      granulomatous skin disease, cutaneous sarcoidosis.

PMID- 9764145
TI  - Blister fluid for the diagnosis of subepidermal immunobullous diseases: a
      comparative study of basement membrane zone autoantibodies detected in blister
      fluid and serum.
AB  - The subepidermal immunobullous diseases bullous pemphigoid (BP), cicatricial
      pemphigoid (CP), pemphigoid gestationis (PG) and linear IgA disease (LAD) are
      characterized by circulating and in vivo deposition of antibodies to antigens in
      the cutaneous basement membrane zone (BMZ). Indirect immunofluorescence (IMF) of
      serum is a routine diagnostic test to detect circulating BMZ antibodies in these
      diseases. We have compared the titres of IgG and IgA and their subclasses, also
      of IgM and IgE BMZ antibodies in serum and aspirated blister fluid in 35 adult
      patients with subepidermal immunobullous diseases: BP (n = 30), PG (n = 2), CP (n
      = 1), and LAD (n = 2), by indirect IMF on intact and salt-split skin. The
      antibody titre in blister fluid was the same or one dilution less than serum in
      most cases and there was no significant difference between these results (P >
      0.05). IgG1 and IgG4 were the predominant subclasses in both blister fluid and
      serum in BP. Indirect IMF of serum and blister fluid was also carried out on
      trypsinized epidermal cells in a subgroup of patients with BP (n = 19). Typical
      polar fluorescence was obtained in all 14 cases which had positive indirect IMF
      on intact and split skin. Our findings demonstrate that blister fluid can be used
      as an alternative to serum for indirect IMF in subepidermal immunobullous
      diseases. This avoids the need for venesection and has a practical application in
      children and those with poor venous access.

PMID- 9764146
TI  - Dermatological findings correlated with CD4 lymphocyte counts in a prospective 3
      year study of 1161 patients with human immunodeficiency virus disease
      predominantly acquired through intravenous drug abuse.
AB  - Several prospective studies on dermatological findings in human immunodeficiency
      virus (HIV) type 1 infected patients have been published, mostly in populations
      in which the predominant risk factor for HIV infection is homosexuality. We
      attempted to identify cutaneous diseases associated with HIV-1 infection and to
      assess disease progression in a cohort of Spanish patients in whom the
      predominant cause of HIV infection was intravenous drug abuse. We prospectively
      examined 1161 HIV-1-positive patients for 38 months. Seventy-four per cent of
      patients were intravenous drug abusers, whereas heterosexual contact was the only
      risk factor in 14% and homosexuality in 9%. Centers for Disease Control stage II
      disease predominated (51%), whereas stage IV disease was less frequent (39%). The
      mean CD4 count was 353/mm3. We took patients' past and present medical history
      and performed a complete physical examination as well as taking photographs and
      carrying out the necessary diagnostic procedures. CD4 counts/mm3 were measured at
      each visit. A diagnosis of cutaneous disease was made in 799 patients (69%). Oral
      candidiasis and seborrhoeic dermatitis were the most common skin disorders,
      followed by xerosis, drug eruptions, dermatophytosis and the papular eruption of
      acquired immunodeficiency syndrome. Condyloma acuminatum, herpes zoster and
      herpes simplex were the most frequent viral infections. Conditions that have a
      statistically significant association with advanced stage and low CD4 levels
      include drug eruptions, xerosis, light reactions, diffuse alopecia, herpes
      simplex, oral candidiasis, psoriasis, oral hairy leucoplakia, molluscum
      contagiosum, Kaposi's sarcoma, furuncles, candidal intertrigo, folliculitis and
      ungual infection, as well as onychomycosis and tinea pedis or manuum. Dermatoses
      commonly associated with homosexuality, such as Kaposi's sarcoma and oral hairy
      leucoplakia, were rare in our patients.

PMID- 9764147
TI  - Proliferation and differentiation of organoid hair follicle cells co-cultured
      with fat cells in collagen gel matrix culture.
AB  - Using rat skin, we studied the influence of fat cells on the proliferation and
      differentiation of organoid hair follicle cells in a three-dimensional collagen
      gel matrix culture system. We cultured organoid hair follicles embedded in
      collagen gel under each of the following three conditions: cell-free collagen gel
      for control experiments (condition 1); co-culture with fat cells in close
      apposition (condition 2); and co-culture with fat cells in spatial separation
      (condition 3). Outgrowths of epithelial cells from the organoid hair follicles
      associated with perifollicular proliferation of fibroblasts were observed under
      conditions 1 and 3. Under condition 2, proliferation of both organoid hair
      follicle cells and fibroblasts was inhibited, but differentiation of the hair
      follicle cells appeared to be accelerated. Fat cells are considered to have an
      inhibitory effect on the proliferation of perifollicular fibroblasts, which might
      have resulted in the inhibition of hair follicle cell proliferation and also in
      the better maintenance of normal follicular structure and integrity, allowing for
      hair-type differentiation to proceed. A direct accelerating effect of fat cells
      on hair follicle differentiation may also have been responsible. In a
      physiological state (co-culture with keratinocytes on the collagen gel), similar
      results were observed under conditions 1 and 2. The different findings under
      conditions 2 and 3 may be due to either of two possibilities: either the
      concentration gradient of the soluble factors released from fat cells, acting on
      either the hair follicle cells or the perifollicular fibroblasts as an inhibitor
      of proliferation, caused the difference in the results, or direct contact between
      the organoid hair follicle cells and fat cells may have influenced the
      accelerating effect of fat cells on the differentiation of hair follicle cells.

PMID- 9764149
TI  - Potential psychological benefits from early treatment of port-wine stains in
      children.
AB  - There is a commonly held conception among referring doctors that very small
      children with congenital capillary malformations, so-called port-wine stains
      (PWS), should not be treated until they are older. Our experience leads us to
      believe that the flashlamp pulsed dye laser is a safe and effective treatment
      even for infants. We have not encountered any persistent pigmentation changes,
      post-treatment scarring or other adverse effects. It is important to quantify the
      psychological disabilities associated with this disorder to assess the need for
      and the benefits of treatment. Questionnaires were distributed to 259 patients
      and their families who visited our clinic because of their PWS. Patients who were
      on the waiting list for laser treatment, undergoing treatment or had completed
      their treatment received different questionnaires. The response rate was 89%.
      High emotional distress was encountered. During the age period 10-20 years, 73%
      (125 patients) were most disturbed by their PWS. That the PWS influenced their
      life negatively was experienced by 75% (171 patients), and 62% (106 patients)
      were convinced that their life would change radically if their PWS could be
      eliminated. Suffering from low self-esteem (in comparison with the same age
      group) was reported by 47% (87% patients). The PWS made their school life and
      education more difficult according to 28% (51 patients) of the sample. Of the
      families of patients, 76% (106 relatives) considered the patient to be negatively
      affected in some way by the PWS. After the laser treatment, all of these distress
      parameters were significantly relieved, together with a need to cover their PWS,
      their fear of going into conflict or quarrels, their social relationships,
      problems with the opposite sex, rage attacks, depressions and abnormal reactions
      from their peers. We believe there is potential psychological benefit in starting
      the treatments of PWS (including non-facial) at as early an age as possible.

PMID- 9764148
TI  - The use of skin testing in the investigation of cutaneous adverse drug reactions.
AB  - Skin testing with the suspected compound has been reported to be helpful in
      determining the cause of cutaneous adverse drug reactions (ADRs), but the value
      and specificity of these tests need to be determined. In this study, 72 patients
      with presumed drug eruptions (27 maculopapular, 18 urticarial, seven
      erythrodermic, nine eczematous, four photosensitivity, three fixed drug
      eruptions, three with pruritus and one with acute generalized exanthematous
      pustulosis) were assessed. All had drug patch tests; 46 also had prick tests and
      30 had intradermal tests (performed on hospitalized patients using a sterile
      solution of the suspected drug, diluted sequentially) with immediate and delayed
      readings. Among these patients, 52 (72%) had a positive skin test reaction, 43%,
      24% and 67% in patch, prick and intradermal skin tests, respectively. The results
      of skin tests varied with the drug tested and with the clinical type of cutaneous
      ADR, as a significantly higher number of positive patch tests was observed in
      maculopapular rashes than in urticarial reactions (P = 0.001). This study
      supports the value of careful sequential drug skin testing in establishing the
      cause of cutaneous ADR. Guidelines are proposed for performing these tests, and
      these include the use of appropriate negative control patients to avoid false
      positive results.

PMID- 9764150
TI  - The management of established postherpetic neuralgia: a comparison of the quality
      and content of traditional vs. systematic reviews.
AB  - In the face of an exponential increase in published biomedical studies,
      dermatologists frequently turn to review articles in order to keep abreast of
      important developments in the treatment of skin diseases. Traditional review
      articles have recently been criticized on the basis of their incompleteness and
      susceptibility to bias. Such biases can be minimized by employing a systematic
      approach to gathering, combining and interpreting the evidence of treatment
      efficacy. Using eight predetermined quality criteria, we compared the quality of
      10 traditional review with one systematic review of treatments for postherpetic
      neuralgia, which were identified from the Medline database for 1992-96. None of
      the 10 traditional review articles satisfied all eight criteria: one satisfied
      five, two satisfied four and the rest satisfied two or fewer criteria. There was
      a wide variation in the recommendations of the authors for the treatment of
      postherpetic neuralgia, often based on anecdotal evidence and clinical
      experience. On the other hand, the systematic review fulfilled seven of the eight
      quality criteria, failing only to discuss future directives. Furthermore,
      treatment recommendations were made solely on the basis of randomized controlled
      trials, which are considered to be the gold standard for measuring the benefits
      of any intervention. The variation in quality and treatment recommendations of
      traditional reviews is worrying. Systematic reviews should be encouraged in
      dermatology because they provide a summary of evidence of the effects of
      dermatological treatments, which has been derived using explicit methods widely
      accepted within science.

PMID- 9764151
TI  - Severity distribution of atopic dermatitis in the community and its relationship
      to secondary referral.
AB  - Although atopic dermatitis is the most common inflammatory dermatosis affecting
      children, no previous studies have evaluated the relationship between disease
      severity and the referral pattern to secondary health care services. We carried
      out a cross-sectional survey of 1760 children aged 1-5 years selected from the
      age-sex registers of four urban and semiurban general practices in Nottingham.
      Atopic dermatitis was diagnosed by a dermatologist on the basis of symptoms and
      signs of a flexural itchy rash that had been present in the previous 12 months.
      The severity of atopic dermatitis was assessed clinically by the same
      dermatologist on the basis of reported symptoms over the previous 12 months and
      clinical signs, and was graded on a three-point scale as mild, moderate or
      severe. Information on the use of primary and secondary health care services was
      recorded at the time of the interview. The 1-year period prevalence of atopic
      dermatitis was 16.5% (95% confidence interval 14.7-18.2%). The severity
      distribution of atopic dermatitis was: mild 84% (n = 242), moderate 14% (n = 41)
      and severe 2% (n = 7). Of those children with atopic dermatitis, 96% (n = 278)
      had consulted their general practitioner in the previous 12 months and 6% (n =
      17) had been seen in secondary care. Overall, 4% (n = 11) of those children with
      atopic dermatitis had a consultation with a dermatologist. Other sources of
      secondary care referral included the paediatric department (n = 2) and accident
      and emergency department (n = 6). Referral to secondary care was found to be
      positively related to disease severity, with referral occurring in 3% of mild
      cases, 15% of moderate cases and 43% of severe cases. Although the relative
      referral rate of mild and moderately severe disease was low, these cases were
      found to represent a significant proportion (82%) of the total numbers of
      children seen in secondary care. This study has shown that: (i) most cases of
      atopic dermatitis in the community are mild in severity; (ii) referral to
      secondary health care services by general practitioners is infrequent; (iii)
      disease severity is an important determinant of referral to secondary care; and
      (iv) any potential change in the referral pattern of mild/moderate cases of
      atopic dermatitis to secondary care is likely to produce a significant increase
      in workload for dermatology departments.

PMID- 9764152
TI  - Prescribing for out-patients by nursing staff in a dermatology department.
AB  - Nurse prescribing for a small range of products has been introduced in primary
      care, but not in hospitals, in the U.K. We have evaluated the benefits, costs,
      practicality and patient satisfaction with the formal introduction of dermatology
      nurse prescribing in the out-patient treatment facility of a district general
      hospital dermatology department with a wide geographical catchment area. Over a 6
      month period, 91 items were prescribed to 47 patients on 72 occasions
      (items/patient: range 1-8, mean 2, median 1). The cost to the department was
      249.04 Pounds (cost per patient: range 0.39 Pound-24.61 Pounds, mean 5.30
      Pounds). A small number of patients appeared to use nurse prescribing as a
      substitute for medical consultations. A total of 33 of 45 adult patients replied
      to a questionnaire. In 15 respondents, the prescription was necessitated by a
      change in the skin condition and in 10 by the exhaustion of supplies of the
      current medication, and both of these factors applied in six patients. All had
      understood the instructions for the use of the treatment prescribed, and only
      three felt that it had failed to work as anticipated. Only one patient had
      (unspecified) side-effects, caused by a prescription for a topical antipruritic.
      Eight patients were able to defer appointments with their general practitioner as
      a result of the nurse-prescribed item being supplied. Prescribing by
      appropriately trained nurses therefore appears to be a safe and effective
      development in dermatology.

PMID- 9764153
TI  - Comparison of teleconsultations and face-to-face consultations: preliminary
      results of a United Kingdom multicentre teledermatology study.
AB  - The objective of this multicentre study was to undertake a systematic comparison
      of face-to-face consultations and teleconsultations performed using low-cost
      videoconferencing equipment. One hundred and twenty-six patients were enrolled by
      their general practitioners across three sites. Each patient underwent a
      teleconsultation with a distant dermatologist followed by a traditional face-to
      face consultation with a dermatologist. The main outcome measures were diagnostic
      concordance rates, management plans and patient and doctor satisfaction. One
      hundred and fifty-five diagnoses were identified by the face-to-face
      consultations from the sample of 126 patients. Identical diagnoses were recorded
      from both types of consultation in 59% of cases. Teledermatology consultations
      missed a secondary diagnosis in 6% of cases and were unable to make a useful
      diagnosis in 11% of cases. Wrong diagnoses were made by the teledermatologist in
      4% of cases. Dermatologists were able to make a definitive diagnosis by face-to
      face consultations in significantly more cases than by teleconsultations (P =
      0.001). Where both types of consultation resulted in a single diagnosis there was
      a high level of agreement (kappa = 0.96, lower 95% confidence limit 0.91-1.00).
      Overall follow-up rates from both types of consultation were almost identical.
      Fifty per cent of patients seen could have been managed using a single
      videoconferenced teleconsultation without any requirement for further specialist
      intervention. Patients reported high levels of satisfaction with the
      teleconsultations. General practitioners reported that 75% of the
      teleconsultations were of educational benefit. This study illustrates the
      potential of telemedicine to diagnose and manage dermatology cases referred from
      primary care. Once the problem of image quality has been addressed, further
      studies will be required to investigate the cost-effectiveness of a
      teledermatology service and the potential consequences for the provision of
      dermatological services in the U.K.

PMID- 9764154
TI  - A randomized, double-blind study comparing the efficacy, safety and optimal dose
      of two formulations of cyclosporin, Neoral and Sandimmun, in patients with severe
      psoriasis. OLP302 Study Group.
AB  - This study compared the efficacy, safety and optimal dose of two formulations of
      cyclosporin, Sandimmun and Neoral, in patients with severe, chronic plaque-type
      psoriasis. Patients were randomized on a 1:1 basis to 24 weeks of treatment with
      Neoral (n = 152) or Sandimmun (n = 157). The starting dose of each formulation
      was 2.5 mg/kg per day. Dose increases to maintain efficacy were allowed after 4
      weeks. In patients who achieved remission, the dose was down-titrated at 4-week
      intervals from week 16. The maximum permitted dose for each formulation was 5.0
      mg/kg per day. Neoral produced a more rapid response than Sandimmun: remission
      rates were higher for Neoral during the first 8 weeks of treatment. The number of
      dose reductions for safety was similar in both treatment groups, but there were
      more dose increases to maintain efficacy in the Sandimmun group (198) than the
      Neoral group (146). The number of patients with dose reductions after week 16 was
      higher for Neoral (n = 83) than for Sandimmun (n = 73). The frequency and nature
      of adverse events were similar for both treatment groups. The mean dose required
      to control the disease was approximately 10% lower with Neoral and fewer dose
      changes were needed. The increased bioavailability and reduced pharmacokinetic
      variability of cyclosporin provided by the Neoral formulation may facilitate
      short-course, intermittent therapy.

PMID- 9764155
TI  - Deletion pattern of the steroid sulphatase gene in Japanese patients with X
      linked ichthyosis.
AB  - Most caucasian patients with X-linked ichthyosis (XLI) reportedly display large
      genomic deletions involving the entire steroid sulphatase (STS) gene and flanking
      regions. In this study, we investigated the deletion patterns of the STS gene and
      flanking regions in 12 unrelated Japanese patients with XLI using the polymerase
      chain reaction method with 10 markers, including the 5' and 3' ends of the STS
      gene. Eleven of the 12 patients exhibited deletion of this entire gene, whereas
      the twelfth patient showed no evidence of deletion. In 10 of the 12 patients, the
      entire region from DXS1139 to DXF22S1 was deleted, the most common deletion
      pattern observed in caucasian patients, indicating that there are no racial or
      ethnic differences.

PMID- 9764156
TI  - Acne vulgaris in the elderly: the response to low-dose isotretinoin.
AB  - There is a very small number of patients who suffer from acne even in the sixth
      and seventh decades of life. These patients have suffered from acne for most of
      their lives, 30-60 years, and have often received multiple courses of antibiotics
      over many years. We saw 10 such patients over 4 years. One received oral
      isotretinoin 1 mg/kg per day, but was unable to tolerate the adverse effects of
      cheilitis and developed hyperlipidaemia. We subsequently treated nine others with
      oral isotretinoin, 0.25 mg/kg per day, for 6 months; in six the acne had
      virtually cleared by 3-4 months while the other three cleared by 6 months. Up to
      36 months after therapy these patients have remained clear of acne except for one
      who relapsed after 11 months. Therefore, as these patients respond well with few
      side-effects both in the long- and short-term to low-dose isotretinoin, they
      should be treated with isotretinoin, although at the lower starting dose of 0.25
      mg/kg per day compared with younger patients who are treated with 0.5-1 mg/kg per
      day, and the treatment maintained for 6 months.

PMID- 9764157
TI  - Differential response of sebaceous glands to exogenous testosterone.
AB  - To test the hypothesis that the seborrhoea of acne is an end-organ hyper-response
      to androgens, a standardized dose of 2% testosterone cream was applied to the
      forehead of eight prepubertal boys for 6 weeks and the effect determined by
      measurements of sebum excretion rate (SER). Three boys showed a 15-fold increase
      in SER and three boys were non-responders, whereas two boys had SER values
      between those of the responders and non-responders. These data show that
      sebaceous glands are stimulated by androgens to varying degrees and support the
      theory of an end-organ response in acne.

PMID- 9764158
TI  - Itraconazole oral solution for the treatment of tinea capitis.
AB  - Twenty-seven children (12 boys, 15 girls, age range 3-11 years, weight range 10
      40 kg) were treated with itraconazole oral solution 10 mg/mL given as pulse
      therapy for tinea capitis. The dosage regimen was 3 mg/kg per day given once
      daily in a fasting state with each pulse lasting 1 week. The first two pulses
      were separated by a 2-week off-drug period, and the second and third pulses had a
      3-week period without drug between them. For each patient a second and third
      pulse were administered if there was clinical evidence of tinea capitis at the
      time-point when the next pulse was due. The overall severity of tinea capitis at
      pretherapy was classified as mild, moderate or severe with the aetiology being:
      Trichophyton tonsurans, 24 patients; T. violaceum, two patients and Microsporum
      canis, one patient. In 19 evaluable patients, 12 weeks after starting therapy,
      the numbers of pulses of itraconazole oral solution required to produce complete
      cure were, according to the severity of disease, mild tinea capitis (one pulse:
      four patients; two pulses: five), moderate disease (one pulse: two patients; two
      pulses: two; three pulses: two), and severe disease (three pulses: three
      patients). One patient with moderate severity tinea capitis was clinically clear
      after three pulses of therapy but mycological examination was positive. Seven
      patients were lost to follow-up and one discontinued therapy because of nausea.
      Itraconazole oral solution 3 mg/kg per day was generally well tolerated. Three
      children developed gastrointestinal adverse effects which were considered to be
      minor or 'nuisance' effects. The data from this preliminary report need to be
      confirmed in a larger group of patients. It remains to be seen whether
      itraconazole oral solution will become a practical alternative to the antifungal
      agents available in a liquid preparation for the treatment of tinea capitis.

PMID- 9764159
TI  - Sweet's syndrome associated with non-tuberculous mycobacterial infection: a
      report of five cases.
AB  - We report the rare association of Sweet's syndrome with non-tuberculous
      mycobacteria in five patients (three women, two men, aged 25-41 years). Clinical
      and histological evidence supported the diagnosis of Sweet's syndrome in all
      patients. The skin lesions responded well to systemic corticosteroid but recurred
      in two cases. All of our patients had chronic disseminated non-tuberculous
      mycobacterial infection. They initially presented with lymphadenopathy and
      developed involvement in other organs later. All of them were treated as having
      tuberculous lymphadenitis based on pathological findings before definite
      diagnosis was made by culture. The organisms isolated were Mycobacterium chelonae
      in three cases, M. scrofulaceum in one case and M. avium intracellulare complex
      in one case. All the patients gradually improved with treatment but one had
      multiple recurrences. The search for an infectious agent, especially non
      tuberculous mycobacteria, should be performed in cases of Sweet's syndrome that
      appear in association with chronic granulomatous lymphadenitis which is
      recalcitrant to antituberculous drugs.

PMID- 9764160
TI  - Unusual clinical variants of cutaneous leishmaniasis in Pakistan.
AB  - Cutaneous leishmaniasis is endemic in the Baluchistan province of Pakistan and
      poses a great risk to non-immune visitors to the area. The wide spectrum of
      clinical variants of this common disease is at times a diagnostic challenge. A
      total of 1709 patients with cutaneous leishmaniasis were recorded over a 1-year
      period. In 37 (2%) patients the lesions were very unusual, and therefore worth
      reporting. These included acute paronychial, chancriform, annular, palmoplantar,
      zosteriform and erysipeloid forms. The zosteriform and erysipeloid forms have
      rarely been reported previously, but to the best of our knowledge, acute
      paronychial, chancriform, annular and palmoplantar lesions are being reported for
      the first time. The morphologically unusual lesions may be attributed to an
      altered host response or involvement of an atypical strain of parasite in these
      lesions.

PMID- 9764161
TI  - Visceral leishmaniasis with cutaneous lesions in a patient infected with human
      immunodeficiency virus.
AB  - We report a case of visceral leishmaniasis (VL) with cutaneous lesions in a
      patient infected with human immunodeficiency virus (HIV). The cutaneous lesions
      consisted of erythematous papules on the legs. Biopsy of one lesion showed
      abundant Leishmania amastigotes within epithelial cells of an eccrine sweat gland
      in the dermis. Leishmania organisms were also found in a blood smear. Rapid and
      complete clearance of the cutaneous lesions was achieved after antimony therapy.
      Cutaneous lesions in VL are being reported increasingly frequently in patients
      with HIV infection and their significance remains in discussion.

PMID- 9764162
TI  - Pseudotumour of the tongue caused by herpes simplex virus type 2 in an HIV-1
      infected immunosuppressed patient.
AB  - An HIV-1 infected immunosuppressed patient (CD4+ cell counts: 382 cells/microL;
      viral load 94,000 copies/mL) with recurrent perianal herpes simplex virus type 2
      (HSV-2) infections is described, showing an unusual exophytic tumour resembling a
      squamous cell carcinoma in the lateral part of the tongue. He also had persistent
      facial herpes infection, oral candidosis, oral hairy leukoplakia and
      lymphadenopathy. The presence of HSV-2 was detected by polymerase chain reaction
      both in smears and in a tissue biopsy taken from the involved tongue area.
      Treatment with brivudin, a new oral virustatic drug, led to rapid regression of
      the tumour.

PMID- 9764163
TI  - Epidermodysplasia verruciformis-like eruption complicating human immunodeficiency
      virus infection.
AB  - Three human immunodeficiency virus (HIV)-infected patients presented with
      disseminated pityriasis versicolor-like skin lesions. Histological examination
      showed features characteristic of epidermodysplasia verruciformis (EV).
      Hybridization studies demonstrated the presence of human papillomavirus (HPV)
      type 5 (HPV5) DNA in two patients and HPV20 in one. A relative increase in CD8+,
      CD57+ cells, which are known to inhibit cell-mediated cytolysis, was observed in
      all patients. HLA-DQB 0301 haplotype, which has been associated with EV, was
      detected in two patients. The findings suggest that infection with EV-associated
      HPV types can complicate HIV infection. Both cellular immune defects and a
      hitherto unknown genetic background might explain the occurrence of EV in HIV
      infected patients.

PMID- 9764164
TI  - Vulval and vaginal adenosis.
AB  - Vaginal adenosis is defined by the presence of metaplastic cervical or
      endometrial epithelium within the vaginal wall, thought to be derived from
      persistent Mullerian (synonymous with paramesonephric) epithelium islets in
      postembryonic life. Spontaneous vaginal adenosis appears to be a fairly common
      (present in about 10% of adult women) but mostly insignificant coincidental
      finding. In women prenatally exposed to diethylstilboestrol (DES), vaginal
      adenosis may arise in up to 90% and is associated with a high risk of vaginal
      carcinoma. Since the withdrawal of DES from the market, vaginal adenosis has
      virtually disappeared from the medical literature. A case of vaginal adenosis is
      presented in a middle-aged woman who had not been prenatally exposed to DES. The
      lesions differed from the spontaneous type by their sudden appearance, their
      extent and their pronounced subjective symptoms. It is speculated that protracted
      oral contraceptive intake may have played a causative role.

PMID- 9764165
TI  - Proteus syndrome: diagnosis in adulthood.
AB  - We describe a 24-year-old woman with many of the classical features of the
      Proteus syndrome. In childhood she had undergone bilateral forefoot amputations
      because of massive bilateral cerebriform hypertrophy of the feet. Other features
      include abnormally large fingers on one hand, a lymphangioma circumscriptum, an
      epidermal naevus, prominent venous varicosities and scattered lipomas. The
      disorder occurs sporadically and is thought to be secondary to a postzygotic
      mutation that survives by mosaicism.

PMID- 9764166
TI  - Trichothiodystrophy without associated neuroectodermal defects.
AB  - Trichothiodystrophy leading to generalized trichorrhexis nodosa-like hair changes
      with abnormal hair breakage is described in a 4-year-old girl. A marked
      deficiency of sulphur and the sulphur-containing amino acid, cystine, was
      detected in the biochemical analysis of the hair. Further investigation of the
      hair showed the morphological criteria of trichothiodystrophy. Commonly related
      symptoms, such as mental retardation, ichthyosis and increased sensitivity to
      sunlight, were not present in our patient.

PMID- 9764167
TI  - Pseudoxanthoma elasticum-like papillary dermal elastolysis: report of four
      Japanese cases and an immunohistochemical study of elastin and fibrillin-1.
AB  - We report four patients with pseudoxanthoma elasticum-like papillary dermal
      elastolysis (PDE). Multiple small papules on the neck, clinically resembling
      pseudoxanthoma elasticum, and loss of the elastic fibre network in the papillary
      dermis were found in each case. Immunohistochemical staining for elastin and
      fibrillin-1 in one patient demonstrated the disappearance of elastin and
      fibrillin-1 in the papillary dermis. Site-matched normal skins of the elderly
      showed intact elastin but a lack of fibrillin-1 in the papillary dermis. The
      younger normal skins revealed intact elastin and fibrillin-1. The results suggest
      that fibrillin-1 is absent from the papillary dermis of the normal-appearing neck
      skin of the elderly and that the primary defect in PDE may be in elastin rather
      than in fibrillin-1.

PMID- 9764168
TI  - Erythropoietic protoporphyria improving during pregnancy.
AB  - Erythropoietic protoporphyria is an uncommon disorder which causes a
      photosensitive cutaneous reaction, and occasionally hepatic dysfunction in
      affected individuals. We report a patient with erythropoietic protoporphyria who
      improved symptomatically during her two pregnancies. In the latter pregnancy,
      quantitative levels of plasma and erythrocyte protoporphyrins were reduced by
      more than half during the pregnancy compared with the levels before pregnancy and
      during lactation.

PMID- 9764169
TI  - Hyperpigmentation due to topical calcipotriol and photochemotherapy in two
      psoriatic patients.
AB  - The vitamin D3 analogue calcipotriol (calcipotriene) is an effective topical
      treatment for psoriasis. In combination with other antipsoriatic agents, such as
      ultraviolet radiation, calcipotriol is reported to improve the overall efficacy
      of the treatment. Here we describe two patients treated with a combination
      treatment of calcipotriol and bath psoralens and ultraviolet A who developed
      hyperpigmentation at the lesional sites where calcipotriol ointment was applied.

PMID- 9764170
TI  - Cutaneous lesions in giardiasis. Report of two cases.

PMID- 9764171
TI  - Severe acral pruritus associated with parvovirus B19 infection.

PMID- 9764172
TI  - Red finger syndrome associated with necrotizing vasculitis in an HIV-infected
      patient with hepatitis B.

PMID- 9764173
TI  - The prevalence of skin diseases in human immunodeficiency infection and its
      relationship to the degree of immunosuppression.

PMID- 9764174
TI  - Proximal subungual onychomycosis due to Aspergillus niger: report of two cases.

PMID- 9764175
TI  - Exophiala werneckii causing tinea nigra in Scotland.

PMID- 9764176
TI  - Bullous pemphigoid blisters of the same duration have similar cytokine
      concentrations which decrease in older blisters.

PMID- 9764177
TI  - Abrupt onset of severe Behcet's disease: preceding oral ulceration is not
      essential for diagnosis.

PMID- 9764178
TI  - Panniculitis in dermatomyositis: report of two cases.

PMID- 9764179
TI  - Pyoderma gangrenosum associated with myelofibrosis.

PMID- 9764180
TI  - Kasabach-Merritt syndrome associated with angioblastoma.

PMID- 9764181
TI  - Familial cavernous haemangiomas.

PMID- 9764182
TI  - The Woronoff zone surrounding the psoriatic plaque.

PMID- 9764184
TI  - Dermatitis simulata.

PMID- 9764183
TI  - Severe pustular psoriasis provoked by oral terbinafine.

PMID- 9764185
TI  - Quo vadis classical physiology?

PMID- 9764186
TI  - Of mice and men--the future of cardiovascular research in the molecular era.

PMID- 9764187
TI  - Mouse models of angiogenesis, arterial stenosis, atherosclerosis and hemostasis.
AB  - The development of efficient transgenic technologies in mice has allowed the
      study of the consequences of genetic alterations on cardiovascular
      (patho)physiology, although the development of such models have been hampered by
      size limitation of species resulting in time-consuming, labor-intensive and
      costly analyses. This overview summarizes the murine models currently available
      for studying or manipulating angiogenesis, arterial stenosis, atherosclerosis,
      transplant arteriopathy, thrombosis, thrombolysis and bleeding and addresses
      techniques to evaluate vascular development during embryogenesis.

PMID- 9764188
TI  - Cardiovascular phenotyping in mice.
AB  - Progress in molecular genetics has changed cardiovascular research. The mouse has
      turned out to be an invaluable model for mammalian genetic modifications to mimic
      and analyse cardiovascular pathology. Through the introduction of transgene and
      gene targeting technology, regulatory systems can be studied at the molecular
      level. Recent technical developments have down-sized the equipment for
      physiological measurements to the mouse level. Micro-surgery has developed to the
      level where most manipulations previously performed in larger animals can now be
      applied to mice. However, different investigators report considerable differences
      in values for physiological parameters. Whether these differences are related to
      the variation in mouse strains or experimental procedures remains to be
      established, but awareness of the variation can be relevant for prospective mouse
      investigators. In the present review, the physiological measurements performed in
      mice to date are discussed and complemented with results from genetically
      manipulated animals. In addition the various surgical procedures and their
      practical application are illustrated.

PMID- 9764189
TI  - Why do animal models of post-angioplasty restenosis sometimes poorly predict the
      outcome of clinical trials?

PMID- 9764190
TI  - Animal models of human cardiovascular disease, heart failure and hypertrophy.
AB  - The progress made in our understanding of the pathophysiology and treatment of
      congestive heart failure (CHF) would not have been possible without a number of
      animal models of heart failure and hypertrophy, each one having unique advantages
      as well as disadvantages. The species and interventions used to create CHF
      depends on the scientific question as well as on factors such as ethical and
      economical considerations, accessibility and reproducibility or the model. How
      closely the model should mimic the human syndrome of CHF depends on the
      scientific question under investigation. If the goal is to study
      pathophysiological processes like remodeling or the function of subcellular
      systems such as excitation contraction-coupling processes, contractile protein
      function or energetics, the model of heart failure should mimic the clinical
      setting as closely as possible. However, if defined causal connections are under
      investigation such as structure-function analyses or regulation of gene
      expression, exact reflection of the clinical setting by the animal model may be
      less important. In this review, animal models of heart failure are discussed with
      particular focus on similarities between the animal model and the failing human
      heart regarding myocardial function as well as molecular and subcellular
      mechanisms. In addition, new models of heart failure and hypertrophy, and finally
      some recent animal models of myocarditis are reviewed.

PMID- 9764191
TI  - Lessons from rat models of hypertension: from Goldblatt to genetic engineering.
AB  - Over the past 50 years various animal models of hypertension have been developed,
      predominantly in the rat. In this review we discuss the use of the rat as a model
      of hypertension, and evaluate what these models have taught us. Interestingly,
      the spontaneously hypertensive rat (SHR) is by far the most widely used rat
      model, although it reflects only a rare subtype of human hypertension, i.e.
      primary hypertension that is inherited in a Mendelian fashion. Many other aspects
      of the etiology of hypertension are found in other rat models, but these models
      are less frequently employed. The widespread use of the SHR suggests that this
      rat model is often chosen without considering alternative (and possibly better
      suited) models. To illustrate the importance of the choice for a particular
      model, we compared the natural history and response to antihypertensive drugs in
      different rat models of hypertension (SHR, Dahl, deoxycorticosterone acetate
      (DOCA)-salt, two-kidney one-clip, transgenic TGR(mRen2)27. This revealed that the
      outcome of hypertension can be similar in some respects, as all models exhibit
      cardiac hypertrophy, and all demonstrate impaired endothelium-dependent
      relaxations. However, the more severe forms of end-organ damage such as heart
      failure, stroke and kidney failure, occur only in some models and then only in a
      subset of the hypertensive rats. The effects of antihypertensives varies even
      more in the different models: antihypertensive treatment only attenuates end
      organ damage if it decreases blood pressure. Moreover, if a given
      antihypertensive is effective, it sometimes even attenuates end-organ damage in
      nonhypotensive doses. On the other hand, some agents do decrease blood pressure
      but do not prevent end-organ damage (e.g. hydralazine in SHR). Furthermore, not
      all classes of antihypertensives are equally effective in all rat models of
      hypertension: endothelin-receptor antagonists are not effective in SHR, but have
      beneficial effects in the DOCA-salt model. The comparison of models, and the
      comparison of treatment effects suggests that end-organ damage critically depends
      upon not only on the stress imposed by high blood pressure and its underlying
      biochemical disturbance, but also upon the ability of the organism to recruit
      adequate 'coping' mechanisms. These coping mechanisms deserve greater attention,
      as failure to recruit such mechanisms may indicate an increased risk. The current
      development of transgenic techniques will provide new opportunities, to develop
      specific models to address this balance between stress and coping.

PMID- 9764192
TI  - Rat models of hypertension, cardiac hypertrophy and failure.

PMID- 9764193
TI  - Experimental models for the investigation of brain ischemia.

PMID- 9764194
TI  - Animal models in the study of myocardial ischaemia and ischaemic syndromes.

PMID- 9764195
TI  - Physiopharmacological evaluation of myocardial performance: how to study
      modulation by cardiac endothelium and related humoral factors?

PMID- 9764196
TI  - Physio-pharmacological evaluation of myocardial performance: an integrative
      approach.

PMID- 9764197
TI  - The mouse with trisomy 16 as a model of human hearts with common atrioventricular
      junction.
AB  - OBJECTIVE: To establish if the mouse with trisomy 16 is a suitable animal model
      with which to elucidate the development of a common atrioventricular junction.
      METHODS: The junctional morphologies in the normal human heart and those with a
      common atrioventricular junction are compared and contrasted. These are then
      related to observations made in normal mice and those with trisomy 16. So as
      better to understand development, a full description is given first of the normal
      atrioventricular junctions. Developmental implications are discussed because
      failure of fusion of the endocardial cushions cannot account for all the
      anomalies found in RXR alpha knockout, and in iv/iv mice. RESULTS: Mice with
      trisomy 16 showed evidence of deficiencies of atrioventricular septation and
      possessed a common atrioventricular junction, but the valvar orifices were not
      balanced between the ventricles as is the case in humans. Whilst some mice showed
      affinities with human tricuspid atresia, other cardiac malformations in the mice
      had no counterparts in human cardiac pathology. In humans both "partial" and
      "complete" forms of "atrioventricular canal malformations" share a basically
      common muscular junctional morphology, the differences being due exclusively to
      the way the bridging leaflets are fused to each other and/or the septum.
      CONCLUSIONS: It is simplistic to use the mouse with trisomy 16 as a model for
      cardiac abnormalities seen in humans. A spectrum more comparable to humans is
      found in RXR knockout mice. Study of the iv/iv mouse may help elucidate the
      genetic steps involved in normal and abnormal atrioventricular septation.

PMID- 9764198
TI  - Animal models of cardiac arrhythmias.

PMID- 9764199
TI  - Experimental models of torsade de pointes.
AB  - Torsade de pointes is a potentially life threatening form of polymorphic
      ventricular tachycardia typically seen in the setting of congenital and acquired
      abnormal QT-prolongation. Numerous in vitro studies have investigated basic ionic
      mechanisms underlying delayed repolarization. The role of different ion channels
      and the induction of early afterdepolarizations have been studied in various
      cardiac cells including M cells. In addition, isolated heart models with and
      without electrical stimulation and/or the use of drugs which prolong
      repolarization have been developed in recent years. Some of these models have
      simulated conditions likely to exist in the clinical setting of torsade de
      pointes, such as bradycardia and hypokalemia. In in vivo canine and rabbit
      models, torsade-like polymorphic ventricular tachyarrhythmias have been induced
      by the administration of different agents such as cesium, neurotoxins, e.g.,
      anthopleurin or various class III drugs under conditions designed to mimic the
      clinical situation. In the context of recent advances in the molecular genetics
      of long QT syndrome, those models which have used sodium or potassium channel
      blockers have gained particular interest. Based on all experimental studies it
      seems probable that the first beats of torsade occur due to early
      afterdepolarizations and triggered activity. The development of subsequent beats
      is less clear. Reentry based on inhomogeneity of refractoriness has been
      suggested as the underlying mechanism.

PMID- 9764200
TI  - Characterisation, utilisation and clinical relevance of isolated perfused heart
      models of ischaemia-induced ventricular fibrillation.
AB  - The isolated perfused heart has been used increasingly during the last decade as
      a model for identifying actions of drugs on ventricular fibrillation (VF) induced
      by myocardial ischaemia. In addition, it has been used to explore the mechanisms
      responsible for the initiation and maintenance of VF, the concept of endogenous
      myocardial protection and the phenomenon of preconditioning. This article is a
      review of the available data (effects of drugs, sources of variation, comparison
      with other models and man, etc.) and an attempt to evaluate the possible clinical
      relevance. For several reasons, it is not possible to make a precise judgement on
      the absolute value of the model in terms of its ability to accurately predict the
      effectiveness of drugs in the prevention of sudden cardiac death, the main reason
      being the lack of a positive control, i.e. a drug with proven effectiveness
      against sudden cardiac death caused by VF in man. Nevertheless, the means by
      which one may reliably and reproducibly generate ischaemia-induced VF in
      different isolated heart preparations, and the factors (such as species, heart
      rate, perfusion constituents and involved zone size) that determine the incidence
      of VF are now well documented. Careful selection of species and experimental
      conditions permits the isolated heart of smaller inexpensive animals to function
      as a first line model for detecting anti-VF activity of probable relevance to
      phase 1 arrhythmogenesis (i.e., arrhythmogenesis during the first 30 min of
      ischaemia). In view of the absence of a clinical template from which to evaluate
      how well it predicts drug effectiveness in man, this model's clinical relevance,
      like that of all other preparations and models, can yet be neither accepted nor
      dismissed. Recent publication patterns suggest an increasing use of the model.
      Therefore, recommendations are made to facilitate its effective use.

PMID- 9764201
TI  - A small animal model of non-ischemic cardiomyopathy and its evaluation by
      transthoracic echocardiography.
AB  - BACKGROUND: Costs for large animal studies have escalated. Therefore there is a
      need to develop small animal models of non-ischemic cardiac failure and accurate
      non-invasive techniques that will allow serial quantitation of left ventricular
      function. OBJECTIVES: The purpose of our study was to determine the efficacy and
      reliability of adriamycin for inducing cardiomyopathy in rats. We hypothesized
      that high frequency transthoracic 2-dimensional and M-mode echocardiography would
      allow for serial testing of cardiac function in this small animal model. METHODS:
      Adriamycin was administered at a dose of 2.5 mg/kg intravenously once a week for
      10 weeks in 54 rats. Transthoracic echocardiography by use of a 7.5 MHz
      transducer was performed in 19 rats at baseline and additionally at 12 weeks
      after beginning of adriamycin therapy to measure left ventricular dimensions and
      calculate fractional shortening. RESULTS: The mortality rate during the treatment
      period was 11%, but increased to 52% at 13 weeks. Transthoracic echocardiography
      provided adequate visualization of left ventricular dimensions and cardiac
      function in a parasternal short axis view. In follow-up echocardiography,
      pericardial effusion was detected in 8/19 rats (42%). Compared to baseline, end
      diastolic diameters increased from 0.56 +/- 0.06 to 0.64 +/- 0.08 mm (p < 0.001),
      end-systolic diameters increased from 0.27 +/- 0.03 to 0.42 +/- 0.08 mm (p <
      0.001), and fractional shortening decreased from 52.8 +/- 4.0 to 34.3 +/- 7.1% (p
      < 0.001) at 12 weeks. Electron microscopy in a subset of rats revealed
      cardiomyocyte degeneration, mitochondrial and sarcoplasmatic reticular edema,
      numerous intracellular vacuoles and 'onion-ring' shaped mitochondrial cristae,
      characteristic for adriamycin cardiotoxicity in human patients. CONCLUSION:
      Adriamycin at an intravenous dose of 2.5 mg/kg over 10 weeks can be used to
      create a reliable model of non-ischemic dilated cardiomyopathy with a high
      success rate. For in-vivo diagnostic purposes, transthoracic echocardiography
      provides a reliable technique to non-invasively assess cardiac function
      quantitatively and qualitatively in follow-up studies in rat cardiomyopathy. This
      small animal model can easily be used for testing new therapeutic strategies in
      cardiac failure.

PMID- 9764202
TI  - The atherosclerotic Yucatan animal model to study the arterial response after
      balloon angioplasty: the natural history of remodeling.
AB  - OBJECTIVE: Remodeling in de novo atherosclerosis and in restenosis after balloon
      angioplasty constitutes a change in total arterial circumference which, together
      with plaque growth or neointimal formation, determines the lumen of the artery.
      To better understand the fundamental biology of neointimal formation, remodeling
      and their interaction, animal studies are needed. In this study, we described in
      detail the methodology used and the natural history of neointimal formation and
      remodeling after balloon angioplasty in atherosclerotic Yucatan micropigs.
      METHODS AND RESULTS: Atherosclerosis was induced in 60 peripheral arteries of
      sixteen Yucatan micropigs by a combination of denudation and atherogenic diet.
      Balloon angioplasty was performed in 38 arteries, with serial intravascular
      ultrasound (IVUS) and quantitative angiography before and after intervention and
      at 2, 4, 7, 14 or 42 days follow-up. Remodeling, expressed as late media-bounded
      area (MBA) loss, increased progressively over time. At 42 days, late MBA loss
      after balloon angioplasty was significantly different compared to late MBA loss
      in control arteries, 2.2 +/- 1.0 versus -0.3 +/- 1.1 mm2 and p = 0.02. Late lumen
      loss increased over time and was highest at 42 days after balloon angioplasty
      (2.8 +/- 0.7 mm2). The contribution of neointimal formation to late lumen loss
      decreased over time and the contribution of late MBA loss to late lumen increased
      over time and was highest at 42 days (78%). Medial necrosis was 48% at two days
      after balloon angioplasty and the repopulation of the media was almost completed
      at seven days. CONCLUSION: Remodeling following balloon angioplasty has an early
      onset and progresses with neointimal formation to cause restenosis over the
      standard 42-day time course for Yucatan micropigs. This correlates to six months
      renarrowing in humans. In this model, atherosclerosis and the natural history of
      restenosis, both with respect to neointimal formation and remodeling, resemble
      the human disease quite closely.

PMID- 9764203
TI  - Skeletal muscle myosin heavy chain expression in rats with monocrotaline-induced
      cardiac hypertrophy and failure. Relation to blood flow and degree of muscle
      atrophy.
AB  - BACKGROUND: In congestive heart failure (CHF) the skeletal muscle of the lower
      limbs develops a myopathy characterised by atrophy and shift from the slow to the
      fast type fibres. The mechanisms responsible for these changes are not clear yet.
      OBJECTIVES: We investigated the influence of blood flow and degree of muscle
      atrophy on the myosin heavy chains (MHC) composition of the soleus and extensor
      digitorum longus (EDL) of rats with right ventricle hypertrophy and failure.
      METHODS: CHF was induced in 16 rats by injecting 30 mg/kg monocrotaline. Eight
      animals had the same dose of monocrotaline but resulting in compensated right
      ventricle hypertrophy. Two age- and diet-matched groups of control animals (nine
      and five respectively) were also studied. The relative percentage of MHC1 (slow
      isoform), MHC2a (fast oxidative) and MHC2b (fast glycolytic) was determined by
      densitometric scan after electrophoretic separation. The relative weights of
      soleus and EDL (muscle weight/body weight) were taken as an index of muscle
      atrophy. Skeletal muscle blood flow was measured by injecting fluorescent
      micropheres. RESULTS: CHF and Control (Con) rats showed similar degree of atrophy
      both in soleus (0.40 +/- 0.06 vs. 0.44 +/- 0.06 p = NS), and EDL (0.47 +/- 0.04
      vs. 0.45 +/- 0.02, p = 0.09). In CHF rats these two muscles showed a
      statistically significant MHCs redistribution toward the fast type isozymes. In
      fact in EDL of CHF rats MHC2a was 30.5 +/- 6.1% vs. 35.8 +/- 8.6% of the Con (p <
      0.05). MHC2b was however higher (68.5 +/- 6.6% vs. 61.0 +/- 9.6%, p = 0.017). In
      the soleus of CHF rats MHC1 was decreased (87.6 +/- 3.4% vs. 91.9 +/- 5.2%, p =
      0.02), while MHC2a was increased (12.04 +/- 3.5% vs. 7.9 +/- 5.2%; p = 0.028).
      Similar changes were not found in the muscles of the compensated hypertrophy
      animals. No correlation was found between MHC pattern and the relative muscle
      weight in the CHF animals. Soleus blood flow in CHF rats was significantly lower
      than that of Con (0.11 +/- 0.03 ml/min/g vs. 0.22 +/- 0.03 p < 0.05), while no
      differences were found in EDL (0.06 +/- 0.02 ml/min/g vs. 0.08 +/- 0.02, p = NS).
      CONCLUSIONS: In rats with CHF a skeletal muscle myopathy characterised by a shift
      of the MHCs toward the fast type isoforms occurs. The magnitude of the shift
      correlates neither with the degree of atrophy, nor with the skeletal muscle blood
      flow, suggesting that these two factors do not play a pivotal role in the
      pathogenesis of the myopathy.

PMID- 9764204
TI  - Alteration of intracellular Ca2(+)-handling and receptor regulation in
      hypertensive cardiac hypertrophy: insights from Ren2-transgenic rats.
AB  - Abnormal intracellular Ca2(+)-handling appears to be a major cause of systolic
      and diastolic dysfunction in animals and humans with cardiac hypertrophy due to
      pressure overload and heart failure. However, the precise mechanisms which cause
      alteration of Ca2(+)-handling remain unclear. Several lines of evidence suggest
      that activation of neurohormonal systems may play a central role. In particular,
      widespread awareness of the importance of the renin-angiotensin system (RAS) has
      occurred since experimental and clinical studies have detailed the efficacy of
      angiotensin-converting enzyme inhibitors in reducing morbidity and mortality in
      patients with left ventricular dysfunction. To evaluate in vivo the role of
      activated RAS in the regulation of (a) cardiac receptor expression and signal
      transduction mechanisms and (b) Ca2+ homeostasis, transgenic TG(mREN2)27 rats
      harbouring the murine renin Ren2d gene were chosen. These animals develop
      fulminant hypertension and cardiac hypertrophy at an early age despite low levels
      of renin in the plasma. High expression of the transgene in the vasculature and
      the heart is associated with increased local formation of angiotensin II. In the
      Ren2-transgenic model alterations of beta-adrenergic neuroeffector mechanisms,
      Ca2(+)-handling and alpha-adrenergic signal transduction are observed which are
      very similar to those observed in the myocardium of patients with end-stage heart
      failure. Moreover, treatment with specific inhibitors of the RAS, such as
      angiotensin-converting enzyme inhibitors or angiotensin II-receptor antagonists,
      largely reversed these defects. Studies on TG(mREN2)27 rats may provide new
      insights into the pathogenesis of hypertensive heart disease and mechanisms which
      promote disease progression to end-stage heart failure and also may have
      important implications with regard to therapeutics of heart failure in man.

PMID- 9764205
TI  - Natural co-occurrence of aflatoxins and Fusarium mycotoxins (fumonisins,
      deoxynivalenol, nivalenol and zearalenone) in corn from Indonesia.
AB  - Sixteen corn samples collected from Indonesia were analysed for aflatoxins (AF),
      fumonisins (FM), trichothecenes and zearalenone (ZEA) using high-performance
      liquid chromatography and gas chromatography-mass spectrometry. AF were detected
      in 11 (69%) samples at a mean level of 119 ng/g (maximum 487 ng/g) and FM in all
      of the samples at a mean level of 895 ng/g (maximum 2970 ng/g). Deoxynivalenol
      (DON), nivalenol (NIV) and ZEA were each detected in two (12%) samples; 21 and 32
      ng/g, 49 and 169 ng/g, and 11 and 12 ng/g, respectively. All of the AF
      contaminated samples were co-contaminated with FM. Mycological study showed all
      of the AF-contaminated samples were infected with A. flavus/A. parasiticus, and
      the FM-contaminated samples were either infected with F. moniliforme (50%), F.
      proliferatum (12%), F. nygamai (6%) or F. decemcellulare (38%). Supportive
      mycological studies showed that Fusarium species isolated from Indonesian corn
      were capable of producing a mean level of 10,000 micrograms/g FM. Based on these
      results, the correlation between FM-producers and AF-producers on kernel
      infection and contamination of these mycotoxins in corn was discussed. This is
      the first report on the natural co-occurrence of AF and various Fusarium
      mycotoxins, including DON and NIV in corn from Indonesia, and also the first
      report on the natural occurrence of DON in corn from hot areas of Southeast Asia.

PMID- 9764206
TI  - The occurrence of fumonisin B1 in maize-containing foods in The Netherlands.
AB  - Seventy-eight maize-containing foods obtained from retail stores in The
      Netherlands were analysed for fumonisin B1 contamination. Thirty-six per cent of
      the samples were contaminated with fumonisin B1 in the range of 8 micrograms kg-1
      (limit of detection) to 1430 micrograms/kg-1. Forty-six per cent of the minimally
      treated maize samples (n = 39; maize for bread production, maize for popcorn,
      maize flour and polenta) were contaminated with fumonisin B1 in the range of 8
      380 micrograms kg-1. Twenty-six per cent of the maize-containing processed foods
      (n = 39; tostada, canned maize, maize starch, maize bread, popped maize, flour
      mixes, maize chips and cornflakes) were contaminated with fumonisin B1 in the
      range of 8-1430 micrograms/kg-1. This survey shows that maize-containing foods in
      The Netherlands frequently can be contaminated with fumonisin B1.

PMID- 9764207
TI  - Fumonisin B1 in maize for food production imported in The Netherlands.
AB  - Sixty-two samples of maize imported in The Netherlands and intended for human
      consumption were screened for the presence and concentration of fumonisin B1.
      Sixty-one of those samples contained fumonisin B1 with concentrations ranging
      from 30 to 3350 micrograms kg-1, 11 maize samples contained > 1000 micrograms kg
      1. The average fumonisin B1 concentration was 640 micrograms kg-1 for the
      positive samples and 620 micrograms kg-1 for all samples. Medians were 600
      micrograms kg-1 and 550 micrograms kg-1 for positive and all samples,
      respectively. The results obtained were comparable to results from other studies
      in maize from various countries.

PMID- 9764208
TI  - Zeranol is formed from Fusarium spp. toxins in cattle in vivo.
AB  - Zeranol, a semi-synthetic oestrogenic growth promoter, was banned in the EU in
      1988. The ability of Member States to police the ban on zeranol has been hampered
      by suggestions from New Zealand and from this laboratory that zeranol may be
      formed by the in vivo metabolism of naturally occurring Fusarium spp. toxins. The
      present study demonstrates that zeranol is formed from alpha-zearalenol and
      zearalenone in vivo and is detected in bovine bile following the oral
      administration of these compounds. However, it is not detected following
      administration of beta-zearalenol. These data suggest that hydrogenation of alpha
      zearalenol, probably in the rumen, is responsible for the appearance of zeranol.
      The present study shows that environmental contamination with Fusarium spp.
      toxins is widespread in Northern Ireland. Fusarium spp. toxins were present in
      32% (n = 422) of all bovine bile samples tested for zeranol during 1995. Zeranol
      itself was confirmed in 6.6% (n = 28) of the samples. However, the mean alpha
      zearalenol and beta-zearalenol concentrations in the bile of zeranol-positive
      animals were 12 and 9 times higher, respectively, than those in the zeranol
      negative animals. The alpha-zearalenol concentration always exceeded the zeranol
      concentration by at least 5:1. This may, in the future, permit differentiation
      between zeranol abuse and natural contamination.

PMID- 9764209
TI  - A collaborative study of an HPLC method for determination of ochratoxin A in
      wheat using immunoaffinity column clean-up.
AB  - Thirteen laboratories within the United Kingdom participated in a collaborative
      study to determine ochratoxin A in wheat using an HPLC method incorporating
      immunoaffinity column clean-up. Mean recovery of ochratoxin A from wheat spiked
      at a level of 5 micrograms/kg was 91% for the method when using the OchraTest and
      93% for the OCHRAPREP brands of column. Four samples naturally contaminated with
      ochratoxin A consisting of two blind duplicates containing concentrations of
      approximately 3 and 6 micrograms/kg of ochratoxin A were examined using a
      specified method. The relative standard deviations obtained within laboratories
      (repeatability) ranged between 9.7 and 12.5%, there being no significant
      difference between the two brands of immunoaffinity column. The relative standard
      deviations obtained between laboratories (reproducibility) were larger, ranging
      from 24.6 to 32.1% when using the OchraTest column and 14.0 and 19.6% for the
      OCHRAPREP column. When results were corrected for recovery, the apparent
      difference in reproducibility between the two columns was much reduced, 14.0
      17.3% for OchraTest and 10.4-17.5% for OCHRAPREP. Horrat values for
      reproducibility were between 0.4 and 0.7 before correcting results for recovery
      and were between 0.3 and 0.6 after correction. The performance of the
      immunoaffinity column method tested compared very favourably with results of
      other published collaborative studies on mycotoxins.

PMID- 9764210
TI  - A highly sensitive gas chromatographic determination of levamisole in milk.
AB  - An efficient extraction and sensitive gas chromatographic method is described for
      the determination of the anthelminthic drug levamisole in milk. Levamisole was
      extracted from alkaline milk with ethyl acetate. Clean-up of the extract was by a
      series of liquid-liquid extraction steps. Levamisole residues in the extract were
      determined by gas chromatography with a nitrogen-phosphorus detector. This method
      was satisfactory for determining levamisole residues in milk as low as 0.5 ng/g.
      Mean recoveries of 0.5-10.0 ng/g fortified milk samples ranged from 84.5 to
      95.2%. Five replicate analyses performed on a milk containing incurred levamisole
      residues yielded a mean of 3.34 ng/g levamisole with a CV of 3.0%.

PMID- 9764211
TI  - Probenecid markedly reduces urinary excretion of ethinylestradiol and
      trimethoprim slightly reduces urinary excretion of clenbuterol.
AB  - This study investigated whether the illegal application of ethinylestradiol or
      clenbuterol in cattle as growth promotors may be concealed by co-treatment with
      drugs that affect urinary excretion. Therefore, six male veal calves were fed
      with ethinylestradiol and six different male veal calves were fed with
      clenbuterol for 13 days. Both groups received the growth promotors twice daily
      (days -2 to 11) with milk replacer. The calves receiving ethinylestradiol were
      additionally fed with probenecid on days 7-11, and the calves receiving
      clenbuterol were additionally fed with trimethoprim (days 7-11). During days 1-11
      of the experiment, 24-h urine and blood samples (once daily) were collected and
      analyses for ethinylestradiol and clenbuterol by specific enzyme immunoassay. In
      four calves the average urinary excretion of ethinylestradiol during days 7-11
      (co-treatment with probenecid) was only about 25% of their average urinary
      excretion of ethinylestradiol on days 1-6. In the other two calves of this group,
      the excretion of ethinylestradiol was reduced to 4% on days 7-11 compared with
      days 1-6. In these two calves several urine samples provided concentrations of
      ethinylestradiol around the limit of detection. As a consequence, there may be a
      chance of concealing ethinylestradiol application by co-treatment with
      probenecid. Co-treatment with trimethoprim led only to a slight reduction of
      urinary excretion of clenbuterol. The detection of clenbuterol in urine samples
      from calves which were co-treated with trimethoprim can thus not be prevented.

PMID- 9764213
TI  - An evaluation of the safety of Crodamol PMP.
AB  - Crodamol PMP (polyoxypropylene (2) myristyl ether propionate) has been
      extensively employed for many years in a wide variety of human cosmetics in the
      absence of reported adverse reactions. The compound is being considered for use
      as a vehicle for veterinary pharmaceuticals in food-producing animals. This paper
      reviews information on the chemistry, metabolism, and toxicity of this compound,
      including the details of a recently completed multi-dose study in rats. Based
      upon this information, it is concluded that Crodamol PMP is a substance of
      apparently low toxic potential. Potential new uses of this compound must compare
      the likely exposure to the substance with the available toxicity information.

PMID- 9764212
TI  - Depletion of penicillin G residues in tissues, plasma and injection sites of
      market pigs injected intramuscularly with procaine penicillin G.
AB  - Procaine penicillin G was administered by intramuscular (i.m.) injection to
      groups of healthy 100 kg market pigs at the approved label dose (15,000 IU/kg
      body weight), once daily for three consecutive days; or an extra-label dose
      (66,000 IU/kg body weight), once daily for five consecutive days. Penicillin G
      residue depletion was followed in plasma, tissue and injection sites using a
      liquid chromatographic method. Groups of pigs were killed 1, 2, 3, 4, 5 and 8
      days after the last injection with the label dose. Penicillin G was not detected
      in liver after 1 day of withdrawal, in muscle and fat after 2 days of withdrawal,
      in plasma after 4 days of withdrawal, in skin after 5 days of withdrawal, or in
      kidney and the injection sites after 8 days of withdrawal. Other groups of pigs
      were killed 1, 2, 3, 5 and 7 days after injection with the extra-label dose. In
      these pigs penicillin G was not found in liver after 2 days of withdrawal, in fat
      after 3 days of withdrawal, or in the muscle, skin, plasma and injection sites
      after 7 days of withdrawal. Penicillin G was found at all times in the kidneys of
      the groups of pigs that received the high dose. The technique used for neck
      injections was critical to obtain intramuscular rather than intermuscular
      injections. The Bureau of Veterinary Drugs, Health Protection Branch, Health
      Canada calculated that the appropriate withdrawal period for pigs was 8 days for
      a dose of 15,000 IU procaine penicillin G/kg body weight and 15 days for a dose
      of 66,000 IU/kg.

PMID- 9764214
TI  - Lead in wine.
AB  - Elevated levels of lead in wine have been explained by several possible
      contamination sources: leaded gasoline, tin-lead capsules (used to cover the
      bottle neck), and brass alloys. Lead measurements from 7000 wines were used to
      identify possible sources and these showed that atmospheric pollution-related
      contamination (leaded gasoline) was not responsible for elevated lead
      concentrations in wine. It also was shown that the presence or absence of tin
      lead capsules as well as the state of tin-lead capsule corrosion had only a very
      minor influence on the lead concentration in wine. The reported positive
      correlation between wine age and lead concentration was confirmed by our data.
      However, further statistical analysis revealed that not the age of wine but the
      vintage and the wine colour were the most significant contributing factors. The
      wine age itself was no longer correlated with the lead concentration after
      controlling for the significant variables mentioned. The conclusions drawn agree
      well with the explanation that brass is the main contamination source.
      Inspections of wineries known for elevated lead levels always revealed the
      presence of brass tubes and faucets. There has been a continuing and significant
      reduction of lead levels in wine during the recent 7 years where measurements
      were made.

PMID- 9764215
TI  - Lead and cadmium in beverages consumed in Finland.
AB  - The lead and cadmium contents of carbonated beverages, juices, beers and wines
      were determined by ETAAS using Zeeman background correction, peak height mode and
      the method of standard additions for quantitation. Other beverages were digested
      in conc. HNO3, but wines were diluted with 10% HNO3. The lead contents of
      beverages were negligible. The mean Pb content of juices was 9 micrograms/kg, 2
      micrograms/kg in carbonated beverages, < 1 microgram/kg in mineral water and 3
      and 4 micrograms/kg in domestic and imported beers. The mean lead content was 16
      micrograms/l in domestic miscellaneous wines, 33 micrograms/l in imported white
      wines, 9 micrograms/l in domestic red wines and 34 micrograms/l in imported red
      wines. The cadmium contents in all beverages were < 1 microgram/kg, except for
      domestic red wine made from raspberry, which contained 2 micrograms/l. Beverages
      contribute only a negligible amount of lead and cadmium to the average Finnish
      diet. However, as the total lead intake is low in Finland, about 12
      micrograms/day, the share of beverages is rather high, about a fifth of the total
      intake.

PMID- 9764216
TI  - Analytical methods for the determination of 3-chloro-1,2-propandiol and 2-chloro
      1,3-propandiol in hydrolysed vegetable protein, seasonings and food products
      using gas chromatography/ion trap tandem mass spectrometry.
AB  - The EC Scientific Committee for Foods and more recently the Food Advisory
      Committee in the UK have proposed that levels of 3-chloro-1,2-propanediol (3
      MCPD) in foods and ingredients should be reduced to the lowest possible. This
      paper reports on the development of methods for the determination of parts-per
      billion (microgram/kg) levels of 3-MCPD in hydrolysed vegetable protein (HVP),
      flour, bread, meat and starch products using gas chromatography/ion-trap tandem
      mass spectrometry (GC/ITMS/MS). Mass spectrometer conditions for detecting 3-MCPD
      and the stable isotope internal standard (3-chloro-1,2-propandiol-d7) were
      established. Candidate extraction methods were initially evaluated for recovery
      and repeatability by spiking selected commodities at a level of 100
      micrograms/kg. Extracts of ingredients and foods prepared by the candidate
      extraction methods were examined by GC/ITMS/MS using samples spiked at a level of
      25 micrograms/kg. The results showed that detection limits of between 3 and 5
      micrograms/kg could be achieved for all commodities.

PMID- 9764217
TI  - Evaluation of release of antioxidant from high density polyethylene by planar
      chromatography.
AB  - Irganox 1330 (1,3,5-trimethyl-2,4,5-tris(3',5'-ditert-butyl)-4'-hydroxybenzyl)-
      benzene) (I), an alkylphenol compound used as antioxdiant in the production of
      high density polyethylene (HDPE), was the subject of this study. The quantity of
      I given up by polyethylene samples of different thickness to aqueous and
      lipophilic media simulating food was studied by planar chromatography (PC). The
      manner of antioxidant release was also investigated. The chromatographic method
      developed was found satisfactory for the quantification of I in the migration
      studies undertaken, and had quantification limits (12 ng/deposit) suitable for
      quality control of HDPE.

PMID- 9764218
TI  - Thermal stability of polyethylene terephthalate food contact materials: formation
      of volatiles from retain samples and implications for recycling.
AB  - PET packaging materials have been tested for volatile content after exposure to
      high temperatures. Samples included laminates, bottles, and roasting bags, and
      were heated at 120 degrees C, 150 degrees C and 230 degrees C for 50 min,
      according to sample type. Volatiles released from the material were trapped on
      Tenax, identified by GC-MS and assessed against a 10 micrograms/kg migration
      threshold limit. Few volatiles were found for samples composed only of PET.
      Volatiles from laminates varied according to the sample structure, but the main
      substances identified were not related to PET, but probably came from printing
      inks and adhesives. It is concluded that the migration potential of PET in high
      temperature applications is very low and that the formation of volatiles during
      use is unlikely to cause any special problems in polymer recovery in recycling
      schemes, provided that other packaging residues are removed effectively.

PMID- 9764219
TI  - Estimates of maximum limits of food colours use in Brazil through the Danish
      Budget Method and the Bar and Wurtzen-modified method.
AB  - The establishment of the permissible levels for the use of additives in foods
      must be based on the Acceptable Daily Intake (ADI). A method that may be applied
      for this purpose is the Danish Budget Method which estimates the maximum amount
      of the additive that may be added to the food based on the functional properties
      of the additive, and on the categories of the food in which the additive will be
      used. Based on the latest information Bar and Wurtzen propose some modifications
      to the original Budget Method, one of which is the addition of a correction
      factor which takes into account the competition between different food additives
      with the same functional properties. In the present paper, both the Budget Method
      and the Bar and Wurtzen-modified method were applied to evaluate whether the
      maximum levels of food colours use exceeded their ADI or not. Applying the
      original Budget Method, the results showed that the colours Sunset Yellow,
      Amaranth, Erythrosine, Ponceau 4R and Cochineal possibly exceeded the ADI; while
      applying the modified method only the colours Erythrosine and Cochineal would
      exceed the ADI. Brazilian regulatory authorities should be advised to establish
      maximum limits of use for the following categories of colours: Caramel,
      Inorganic, Natural and Artificial Colours Identical to the Natural Ones, where
      ADIs have been evaluated by JECFA.

PMID- 9764220
TI  - Sorbic acid-amine function interactions.
AB  - Sorbic acid has a system of conjugated double bonds which makes it able to
      undergo nucleophilic addition reactions with certain functions. The interactions
      between sorbic acid and amine functions present in the endogenous constituents of
      food were quantified. The formation of new products was demonstrated and the
      underlying mechanisms studied using ethyl sorbate and various amines. HPLC, GC,
      GC-SM and NMR analyses of the reaction mixtures enabled the products to be
      isolated and identified. The addition reactions led, at 20 degrees C, to linear
      monoadducts and, at 50 degrees C and 80 degrees C, to cyclic derivatives
      resulting from double addition.

PMID- 9764221
TI  - Evaluation of the toxicity of drug residues in food: the case for 'relay'
      toxicity studies.
AB  - The tissue residues of veterinary drugs given to food-producing animals are an
      ill-defined mosaic of parent drug and metabolites. Consumers are only ever
      exposed to this mixture in the presence of a vast excess of the excipient, food.
      Given the modifying effects of food on the absorption and disposition of co
      administered xenobiotics, it follows that the toxicity of these residues can only
      be properly evaluated in the presence of a large excess of food. Adoption of a
      relay toxicity strategy addresses these two points. The proposed relay toxicity
      testing approach is as follows. The target species receives a recommended dosage
      regimen of the drug, but a dose level three- to five-fold higher than normal and
      the animals are then killed several days earlier than the projected withdrawal
      period. The tissues from these animals, containing the residue mixture at
      artificially high concentrations, are then administered to laboratory animals for
      conventional toxicological evaluation. In this approach the residues do not
      require individual identification and their potential toxicity is evaluated in
      the presence of the inescapable excipient, food. Determination of an 'exposure'
      level without observerable toxicity provides, in principle, the means of relating
      human safety to a No-Observed Effect Level in laboratory animals in the
      traditional manner.

PMID- 9764222
TI  - The management of civilian intra-articular gunshot wounds: treatment
      considerations and proposal of a classification system.
AB  - The incidence of intra-articular low-velocity gunshot wounds is increasing as the
      number of civilians injured by handguns grows. The severity of these injuries can
      vary and the general principles of managing them, particularly in regards to the
      role of irrigation, debridement and prophylactic antibiotics, are evolving. The
      authors suggest that injuries can be classified according to the ultimate
      location of the projectile, the level of contamination, and the type of fracture
      present. Injuries in which the projectile has no contact with the synovial fluid,
      with a low level of contamination, and a stable fracture pattern may be treated
      non-operatively, with antibiotics only. Wounds in which the bullet remains in
      contact with synovial fluid have a higher level of contamination or have a
      fracture requiring internal fixation and intravenous antibiotics in combination
      with more aggressive surgical treatment.

PMID- 9764223
TI  - Gunshot wounds to the spine.
AB  - In the USA, low velocity gunshot injuries (GSI) account for 13% of all urban
      spinal injuries, and they have become the second leading cause of all spinal cord
      injuries. The initial clinical evaluation should assess vascular, visceral,
      and/or neurological injury. Early imaging studies are required with computerized
      tomography in addition to plain radiographs to assess accurately the location and
      extent of the bone injury. The role of steroids is unclear, and if given, should
      be administered to GSI patients with complete or partial neurological deficit who
      present within eight hours of injury. The indications for prophylactic
      antibiotics have not been well established and although recommended, these are
      deemed essential only in patients with associated visceral perforation. Early
      surgical exploration is most appropriate to address associated vascular or
      visceral injury, while spinal decompression does not appear to influence
      neurological recovery. The majority of GSI spine fractures are stable;
      instability is usually due to ill-advised decompression of cervical spine GSI.
      Retained bullet fragments are rarely problematic; lead toxicity can occur due to
      missile contact with the synovial fluid, disc space, or contact with a
      pseudocyst.

PMID- 9764224
TI  - Humeral fracture secondary to civilian gunshot injury.
AB  - Violence is the leading cause of death in the USA. The cost of violence due to
      gunshot wound is about $425 billion. While the closed fracture of the humerus is
      common, humeral shaft fractures caused by gunshot wound occur infrequently. There
      is much controversy regarding their management, i.e. should these injuries be
      treated surgically or can they be safely treated with minimal intervention. The
      aim of this study is to review our experience in the management of fourteen
      patients with a humeral fracture due to gunshot wounds. Of fourteen, seven
      patients were treated with local debridement, oral antibiotics and fracture
      brace. The remaining seven patients underwent surgical stabilization of the
      fracture. The time to union was similar in both groups (6 weeks in non-operative
      to 9 weeks in open treatment). In conclusion, fracture of the humeral shaft
      secondary to low velocity gunshot wound in the civilian setting can safely be
      treated as a closed fracture with local wound care and oral antibiotics.

PMID- 9764225
TI  - Management of civilian gunshot injuries of the femur. A review of the literature.
AB  - Gunshot fractures of the femur are becoming more commonplace in modern
      civilization. The initial assessment must accurately document the vascular and
      neurological status of the limb as well as the characteristics of the fracture.
      Low velocity gunshot wounds require a brief course of broad spectrum intravenous
      prophylactic antibiotics and limited surgical debridement of the wound.
      Definitive stabilization should consist of locked, reamed, intramedullary nailing
      for low velocity injuries, and non-reamed nailing for high velocity injuries.
      External or plate fixations are best reserved for the more severe Grade IIIC
      injuries. Successful limb salvage is most dependent on the associated vascular
      injury, while neurological injury is a major determinant of long-term disability.

PMID- 9764226
TI  - 'Traumaphobia' disease of surgeons; can it be cured? 1996 William Gissane
      Lecture.

PMID- 9764227
TI  - MRI of cerebrum and cervical columna within two days after whiplash neck sprain
      injury.
AB  - The present study was undertaken to evaluate if MRI within 2 days of a motor
      vehicle accident could reveal pathology of importance for understanding long-term
      disability after whiplash neck-sprain injuries. As part of a prospective study
      cervical and cerebral MRI was performed on 40 neck sprain patients with whiplash
      injury after car accidents. The imaging was done within 2 days of the injury to
      make sure that any neck muscle bleeding, oedema or other soft tissue injuries
      could be detected. The MRI findings from the patients were both correlated to
      reported symptoms 6 months after the accident and compared to a control group of
      20 volunteers. The MRI of both brain and neck revealed no significant differences
      between the patients and the control group. When the patients were grouped
      according to the main MRI findings at intake and compared according to the
      development of subjective symptoms reported by the patients, the only significant
      difference was more headaches at 6 months in the groups with disk pathology or
      spondylosis when compared to the group with no pathology. In conclusion, MRI
      within 2 days of the whiplash neck-sprain injury could not detect pathology
      connected to the injury nor predict symptom development and outcome.

PMID- 9764228
TI  - Failure of femoral head fixation: a cadaveric analysis of lag screw cut-out with
      the gamma locking nail and AO dynamic hip screw.
AB  - The most commonly reported failure mode of sliding hip screws in published
      literature is cut-out of the lag screw. This study investigates the resistance to
      failure of the femoral head, with lag screws used in two types of sliding hip
      screws, the gamma locking nail (Howmedica) and the dynamic hip screw (DHS)
      (Synthes). The investigation consisted of biomechanical tests under static
      loading conditions on 12 pairs of cadaveric femoral heads, to establish the
      failure loads due to screw cut-out for the two implant lag screws. The gamma nail
      appeared to reduce the tendency to cut-out in the osteoporotic bone (soft)
      associated with elderly patients in whom these devices are commonly used (p <
      0.05). In high density bone (hard) the gamma lag screw also appeared to be
      stronger, because the DHS showed a tendency to bend. The larger diameter of the
      gamma nail lag screw resists bending and appears to reduce the risk of cut-out
      compared with the DHS.

PMID- 9764229
TI  - Management of combined penetrating cardiac and abdominal trauma.
AB  - This is a retrospective review of patients with combined penetrating cardiac and
      abdominal trauma. Clinical presentation patterns are described and a management
      strategy is outlined. The series comprises 25 patients. On the basis of the
      mechanism of injury and the prognosis, the patients were divided into two groups:
      'low risk' (single high epigastric stab wound) and 'high risk' (multiple stabs,
      single or multiple gunshot wounds). There were six patients in the low-risk
      group. Their intra-abdominal injuries were moderately severe. None of this group
      died. There were 19 patients in the high-risk group. Three underwent emergency
      room thoracotomy and died. Of the remaining patients, four underwent a
      thoracotomy first for cardiac tamponade or massive haemothorax and 12 underwent a
      laparotomy first because of massive haemoperitoneum. The mortality in this group
      was 63 per cent. It is essential to recognize the cardiac injury in low-risk
      patients; the cardiorrhaphy must be performed before the laparotomy. In high-risk
      patients, the sequence of operations depends on the clinical presentation.
      Obvious cardiac tamponade or massive haemothorax mandate a thoracic approach
      first, while severe hypovolaemic shock with a massive haemoperitoneum justifies
      the performance of a laparotomy first; a transdiaphragmatic pericardiotomy is
      useful, in these cases, before proceeding to median sternotomy.

PMID- 9764230
TI  - Intramural post-traumatic haematomas of the duodenum: are there any late sequelae
      of operative intervention?
AB  - The data of nine children with post-traumatic intramural haematoma of the
      duodenum treated in Aghia Sophia Children's Hospital of Athens from 1967 to 1980
      were retrospectively analysed. Diagnosis was preoperative in all but two
      children, in whom diagnosis was made during laparotomy. All but one were managed
      by operative intervention which consisted of simple evacuation of the haematoma
      and closure of the serosal incision in two out of eight children. Six out of
      eight children operated on were followed up for 15 years, during which they were
      free of symptoms. Hypotonic duodenography performed in the above patients was
      negative for deformity or stricture of the duodenum.

PMID- 9764231
TI  - Is routine computed tomographic (CT) scanning necessary in suspected basal skull
      fractures?
AB  - The aim of this prospective observational study was to assess the yield of
      routine fine-cut computed tomographic (CT) scans in patients with suspected basal
      skull injuries. Over an 8 month period in 1994, 500 consecutive head-injured
      patients were examined for clinical signs of basal skull fracture and underwent
      fine-cut (5 mm) CT scans through the skull base in addition to standard (10 mm)
      cuts through the vault. Clinical signs were present in 144 patients (144/500,
      28.8 per cent) of which 75 (75/144, 52 per cent) had corresponding CT evidence of
      fracture. A further 22 patients (22/500, 4.4 per cent) had no clinical signs but
      fractures were seen on CT. The presence of cranial nerve injury, cerebrospinal
      fluid leak, epistaxis, periorbital bruising, and two or more signs, were more
      likely to be associated with positive CT scans (P < 0.001, chi 2 tests). The
      incidence of associated mass lesions was 50.5 per cent, of which 55.1 per cent
      required craniotomy. This was significantly higher than in patients without
      evidence of skull base fracture (16.6 per cent) (P < 0.001, chi 2 27.165). Six
      patients, two of whom had meningitis, required surgical repair of the dural
      defects seen on CT. The diagnostic yield of routine fine-cut CT scans in this sub
      type of head injury is 52 per cent, and is of value in detecting associated mass
      lesions or significant dural defects which may require surgical intervention.

PMID- 9764232
TI  - Stress fracture of the sternum: an unusual injury?
AB  - Stress fracture of the sternum is a rare condition which presents as acute
      anterior chest pain after repetitive upper-body exercise. Two case reports are
      presented and it is postulated that this is an often underdiagnosed condition
      which should be considered in the differential diagnosis of acute chest pain in
      the athlete. Awareness of the injury together with meticulous clinical
      examination supported by good quality radiographs or isotope bone scan may lead
      to an increase in the diagnosis of this injury.

PMID- 9764233
TI  - Isolated fractures of the lesser trochanter in children.
AB  - In a retrospective study of 1126 children with fractures of the proximal third of
      the femur, three children were found to have isolated fractures of the lesser
      trochanter. This fracture occurred from a fall in one child and following
      sporting activities, without a history of injury, in the others. In the latter
      children, the clinical presentations were similar to those of children with
      transient synovitis of the hip or Perthes disease. In each child, plain
      radiographs showed an avulsion fracture of the bony portion of the lesser
      trochanter. Early and complete recovery followed symptomatic treatment even when
      there was marked proximal displacement of the avulsed segment of the lesser
      trochanter.

PMID- 9764234
TI  - Epidemiology and outcome of tibial diaphyseal fractures in footballers.
AB  - A retrospective analysis of tibial diaphyseal fractures caused by football was
      undertaken to establish the epidemiology and severity of these common injuries.
      Analysis showed that the commonest fracture types were Tscherne C0 and C1
      fractures and that only 73.9 per cent of the patients had unimpaired sporting
      function after the injury. The time to return to football was significantly
      related to the severity of the fracture but there was no correlation with the
      skill of the player. The time to return to football for the C0 fractures averaged
      7-8 months and it is therefore suggested that it is unlikely that any player will
      return to football in the same season.

PMID- 9764235
TI  - Aetiology of assault with respect to alcohol, unemployment and social
      deprivation: a Scottish accident and emergency department case-control study.
AB  - In a study to investigate the association between alcohol consumption,
      unemployment and social deprivation and assault in individuals, 70 victims of
      assault attending a Scottish accident and emergency department were identified
      and matched with 70 paired age, sex and time of attendance controls. Seventy per
      cent were male and 30 per cent female. Cases were more likely to have been
      drinking (p < 0.001) and to admit to previous assault (p < 0.001), as reported in
      other studies. Despite living in the same geographical area (p = 0.353), the
      cases were more likely to be unemployed (p = 0.011) and had a higher mean
      deprivation score (p = 0.043). These results indicate that violence is associated
      with unemployment and socio-economic status of the individual and they
      compliement studies based on population data which have linked rates of violence
      with low income and social deprivation.

PMID- 9764236
TI  - A comparison of the relative costs of cast treatment and intramedullary nailing
      for tibial diaphyseal fractures in the UK.
AB  - A retrospective study was undertaken to compare the costs of treating tibial
      diaphyseal fractures non-operatively in a cast or operatively with locked
      intramedullary nailing. In total 39 patients with isolated closed or grade I
      open, two-part, displaced tibial diaphyseal fractures were studied. Of these, 18
      were treated by manipulation under anaesthesia and cast immobilization, and 21 by
      closed, reamed, locked intramedullary nailing. A detailed analysis of the cost of
      treatment of each patient was performed and analysed in terms of the in-hospital
      costs and the overall costs, taking into account time off work. The mean hospital
      costs were 2226 pounds for plaster treatment and 3727 pounds for intramedullary
      nailing (significantly different, p < 0.05). The mean time off work was 9 weeks
      longer in the plaster group and when the cost of lost production through time off
      work was added to the hospital costs, the overall costs of plaster treatment and
      intramedullary nailing were 6810 Pounds and 6592 Pounds (difference not
      significant). This study suggests that the cost to the hospital of treating these
      fractures is less with plaster treatment but that the overall cost to the
      community is no different.

PMID- 9764237
TI  - An epidemic of roller-blade injuries in children.
AB  - Roller blading is a new and increasingly popular leisure activity in many
      countries. We reviewed 110 consecutive patients with roller-blade injuries
      between 1 January and 30 June 1996. The patients ranged from 4 to 14 years in age
      (mean 6.5 years). Eighty-three (75.4%) sustained injuries to the upper limb and
      27 (24.5%) injured the lower limb. Fifty-six patients, were girls and 54 were
      boys. Of the 110 patients, 79 (72.7%) sustained fractures, 28 (25.4%) soft tissue
      injuries and 3 (2.7%) dislocations. Eighty-three (75.4%) of the patients wore no
      protective equipment on the limbs. Four months following injury 103 (93.6%)
      patients were fully recovered. The mean duration of school absence was 3 days.
      Subsequently 101 children returned to using roller-blades following injury.
      Seventy-three (66.3%) of these now use protective equipment. We found that
      injuries were unrelated to age or duration of roller-blading experience or to the
      brand-name of roller blades used, and that most of our patients wore no
      protective equipment at the time of injury.

PMID- 9764238
TI  - Methods and results of the treatment of peacetime and wartime multiple injuries-
      a comparative study.
AB  - Seventy-one patients suffering from multiple injuries were divided into two
      groups, according to the manner in which the injuries were inflicted. Forty-one
      were injured in 'peacetime' circumstances (road traffic accidents, 85.4 per
      cent), and 30 patients were injured during 'military' shelling or in combat.
      Since there is no generally accepted severity scoring of wartime multiple
      injuries, this paper has offered one. A 'peacetime' scoring system was used to
      compare the hospital mortality in the two groups. The severity of injuries in
      both groups was estimated by using the Injury Severity Score. There was no
      statistically significant difference between the two groups with regard to injury
      severity, age, hospital mortality rate, received infusion, or the number of
      specialists involved in treatment. The differences between the two groups were
      significant in the application of transfusion and antibiotics, number of
      operations performed, and the time span between injury and operation.

PMID- 9764239
TI  - Inner city gunshot wounds.
AB  - A retrospective survey was undertaken to establish the pattern and incidence of
      gunshot wounds seen at a South London hospital. Forty-two gunshot wounds were
      seen in 1993 and 1994. All the patients were under 39 years of age and 40 were
      male. All patients had low energy transfer injuries, having been shot with hand
      guns (n = 36), seven of whom had multiple bullet or shotgun wounds (n = 6).
      Sixteen patients had head, neck or chest injuries, eight of whom died. Seven
      patients were wounded in the abdomen or pelvis and 31 had limb injuries. Thirty
      six surviving patients had a total of 33 operations and a mean hospital stay of
      7.65 days (range 0-105 days).

PMID- 9764240
TI  - Inferior dislocation of the patella.

PMID- 9764241
TI  - Fracture dislocation of the scaphoid.

PMID- 9764242
TI  - Survival following aortic transection: a case report and literature review.

PMID- 9764243
TI  - Carpometacarpal dislocation producing transient motor neurapraxia of the ulnar
      nerve.

PMID- 9764244
TI  - Traumatic aneurysm of the ulnar artery in a child.

PMID- 9764245
TI  - Dislocation of superior tibio-fibular joint in association with fracture of the
      tibia: 'Monteggia' injury of the leg.

PMID- 9764246
TI  - Phalangeal metaplasia following amputation in a child's finger.

PMID- 9764247
TI  - Compartment syndrome of the hand--a case report.

PMID- 9764248
TI  - An unusual complication of major trauma in a jockey.

PMID- 9764249
TI  - A novel indication for a humeral nail.

PMID- 9764250
TI  - Percutaneous drainage of a duodenal haematoma.

PMID- 9764252
TI  - Two new uses of the AO wire tightener: an operative technique.

PMID- 9764251
TI  - Perforation of the transverse colon as a result of minor blunt abdominal trauma.

PMID- 9764253
TI  - Public health management.

PMID- 9764254
TI  - Why is mortality higher in poorer areas and in more northern areas of England and
      Wales?
AB  - STUDY OBJECTIVE: To identify and quantify the factors responsible for the
      differences in mortality between affluent and deprived areas, the north and the
      south, and urban and rural areas in England and Wales. DESIGN: A multiple Poisson
      regression analysis of cause specific mortality in the 403 local authority
      districts, each classified by deprivation (using the Jarman Index), latitude
      (from 50 degrees to 55 degrees north) and urbanisation, adjusting for age, sex,
      and proportion of ethnic minorities. SETTING: England and Wales 1992. MAIN
      RESULTS: All cause mortality was 15% higher in the districts comprising the most
      compared with the least deprived tenth of the population, 23% higher in the most
      northern (55 degrees) than in the most southern (50 degrees) districts, and 4%
      higher in metropolitan (within large cities) than rural districts. Nationally
      these differences were associated with 40,000, 65,000, and 15,000 excess deaths
      respectively. More than two thirds of the overall excess mortality with
      deprivation, latitude, and urbanisation was from three diseases--ischaemic heart
      disease, lung cancer, and chronic bronchitis and emphysema. The excess mortality
      from these and other diseases closely matched that predicted from differences
      according to deprivation and latitude in smoking, heavy alcohol consumption,
      Helicobacter pylori infection, and temperature, and thus could be attributed to
      these causes. About 85% of the overall excess mortality with deprivation was
      attributable to heavier smoking and 6% to heavier alcohol consumption, but diet
      varied little. Deaths more directly related to deprivation (such as those caused
      by H pylori infection, drug misuse, psychoses) accounted for an estimated 12% of
      the excess deaths, but variation in provision and uptake of healthcare services
      only 1%. The direct effects of deprivation are more strongly related to morbidity
      than mortality. Of the difference in mortality with latitude, about 45% was
      attributable to differences in smoking, and 25% to climate (mainly the
      association of cardiovascular and respiratory disease with cold). The differences
      with urbanisation were mainly because of smoking. CONCLUSIONS: Differences in the
      prevalence of smoking account for much of the variation in mortality between
      areas. Alcohol accounts for some, diet little. The more direct material effect of
      deprivation contributes to the variation in mortality but is particularly
      important with respect to differences in morbidity.

PMID- 9764255
TI  - Behavioural and biological correlates of physical functioning in middle aged
      office workers: the UK whitehall II study.
AB  - STUDY OBJECTIVES: (1) To identify behavioural and biological correlates of poor
      physical functioning and (2) to determine whether such associations are
      independent of disease. DESIGN: Potential correlates were obtained from
      questionnaires and screening visits at baseline and five year follow up. Physical
      functioning was measured at follow up using the 10 item scale from the short-form
      36 health survey. SETTING: London offices at baseline. PARTICIPANTS: 10,308 civil
      servants (6895 men and 3413 women), with a median age (range) of 49 years (39-63)
      at follow up. MAIN RESULTS: Multiple logistic regression showed that cigarette
      smoking, physical activity, body mass index (BMI), triglycerides, fibrinogen, and
      insulin were independently associated with poor physical functioning for men. For
      women, physical activity, eating habits, body mass index, fibrinogen, and insulin
      were independently associated with poor physical functioning. For example, among
      men, current smokers who had smoked more than 20 pack years were 1.89 (95% CI
      1.35 to 2.67) times as likely to have poor physical functioning as never smokers.
      Men with BMI of 30 kg/m2 or more were 1.71 (95% CI 1.13 to 2.59) times as likely
      to have poor physical functioning as those with BMI < 20 kg/m2. The corresponding
      odds ratio for women was 2.66 (95% CI 1.80 to 3.93). With the exceptions of
      fibrinogen and insulin, associations remained on exclusion of subjects with
      physical disease. CONCLUSIONS: Risk factors established for physical diseases are
      associated with poor physical functioning in a population of working age. These
      associations may be independent of current disease.

PMID- 9764256
TI  - School absence and treatment in school children with respiratory symptoms in The
      Netherlands: data from the Child Health Monitoring System.
AB  - STUDY OBJECTIVE: To assess the prevalence of respiratory problems, and the
      relation of these problems with school attendance, medicine use, and medical
      treatment. DESIGN: The Child Health Monitoring System. SETTING: Nineteen public
      health services across the Netherlands. PARTICIPANTS: 5186 school children aged 4
      15 years, who were eligible for a routine health assessment in the 1991/1992
      school year. MAIN RESULTS: Respiratory symptoms were present in 12% of the
      children. Recent symptoms suggestive of asthma (wheezing or episodes of shortness
      of breath with wheezing in the past 12 months, or chronic cough, or a combination
      of these) were reported for 8%. These symptoms were most frequent in the younger
      children, and in children at school in towns with less than 20,000 inhabitants.
      Of the children with recent symptoms suggestive of asthma, 37% reported school
      absence for at least one week during the past 12 months, compared with 16% in
      children without respiratory symptoms. School absence because of respiratory
      illness was reported for 22%, and medicine use for respiratory problems for 38%
      of the children with recent symptoms suggestive of asthma. Of these children, 21%
      were receiving medical treatment, compared with 15% of the asymptomatic children.
      CONCLUSIONS: Respiratory symptoms are a common health problem in children, and
      they are an important cause of school absence and medicine use. However, the
      percentage of children receiving medical treatment seemed quite low, indicating
      that proper diagnosis and treatment are probably still a problem.

PMID- 9764257
TI  - Design, objectives, and lessons from a pilot 25 year follow up re-survey of
      survivors in the Whitehall study of London Civil Servants.
AB  - DESIGN: To assess the feasibility of conducting a re-survey of men who are
      resident in the United Kingdom 25 years after enrollment in the Whitehall study
      of London Civil Servants. METHODS: A random sample of 401 study survivors
      resident in three health authority areas was selected for this pilot study. They
      were mailed a request to complete a self administered questionnaire, and then
      asked to attend their general practice to have their blood pressure, weight, and
      height measured and a blood sample collected into a supplied vacutainer, and
      mailed to a central laboratory. Using a 2 x 2 factorial design, the impact of
      including additional questions on income and of an informant questionnaire on
      cognitive function was assessed. RESULTS: Accurate addresses were obtained from
      the health authorities for 96% of the sample. Questionnaires were received from
      73% and blood samples from 61% of the sample. Questions on income had no adverse
      effect on the response rate, but inclusion of the informant questionnaire did.
      Between 1970 and 1995 there were substantial changes within men in the mean blood
      pressure and blood total cholesterol recorded, as reflected by correlation
      coefficients between 1970 and 1995 values of 0.26, and 0.30 for systolic and
      diastolic blood pressure and 0.38 for total cholesterol. CONCLUSION: This pilot
      study demonstrated the feasibility of conducting a re-survey using postal
      questionnaires and mailed whole blood samples. The magnitude of change in blood
      pressure and blood total cholesterol concentrations within individuals was
      greater than anticipated, suggesting that such remeasurements may be required at
      different intervals in prospective studies to help interpret risks associations
      properly. These issues will be considered in a re-survey of the remaining
      survivors of the Whitehall study.

PMID- 9764258
TI  - Health care expenditures after introduction of a gatekeeper and a global budget
      in a Swiss health insurance plan.
AB  - STUDY OBJECTIVES: To assess whether the introduction of "managed care" (capitated
      budget and utilisation control by general practitioners) in a Swiss health
      insurance plan caused a selective disenrolment of plan members, and whether it
      achieved its goal of reducing health care expenditures. DESIGN: Controlled before
      after analysis of health insurance claims. SETTING: Health insurance plan of the
      University of Geneva, Switzerland, which introduced managed care at the end of
      1992, and comparison plan, which reimbursed health care expenditures without
      setting a budget or controlling access. PARTICIPANTS: Analysis of self selection:
      university plan members who accepted (3993) or refused (659) transfer to managed
      care. Analysis of change in expenditures: cohorts of persons continuously
      enrolled in the university (1575) and comparison (3384) plans in 1992 and 1993.
      MAIN RESULTS: During 1992, the year before the transformation of the university
      plan, persons who refused managed care had generated 35% higher expenditures than
      those who accepted managed care (p < 0.001). Between 1992 and 1993, expenditures
      per member decreased by 9% in the university cohort and increased by 11% in the
      comparison cohort (p = 0.004). Technical procedures (laboratory tests, physical
      therapy, drugs) decreased most in the university plan. No impact on hospital
      admissions was detected. CONCLUSIONS: Introduction of gatekeeping and budget
      management by physicians caused a favourable self selection process for the
      university plan. In addition, the managed care plan achieved a substantial
      decrease in overall health care expenditures in its first year of operation,
      chiefly by reducing outlays for technical procedures.

PMID- 9764259
TI  - The feasibility of creating a checklist for the assessment of the methodological
      quality both of randomised and non-randomised studies of health care
      interventions.
AB  - OBJECTIVE: To test the feasibility of creating a valid and reliable checklist
      with the following features: appropriate for assessing both randomised and non
      randomised studies; provision of both an overall score for study quality and a
      profile of scores not only for the quality of reporting, internal validity (bias
      and confounding) and power, but also for external validity. DESIGN: A pilot
      version was first developed, based on epidemiological principles, reviews, and
      existing checklists for randomised studies. Face and content validity were
      assessed by three experienced reviewers and reliability was determined using two
      raters assessing 10 randomised and 10 non-randomised studies. Using different
      raters, the checklist was revised and tested for internal consistency (Kuder
      Richardson 20), test-retest and inter-rater reliability (Spearman correlation
      coefficient and sign rank test; kappa statistics), criterion validity, and
      respondent burden. MAIN RESULTS: The performance of the checklist improved
      considerably after revision of a pilot version. The Quality Index had high
      internal consistency (KR-20: 0.89) as did the subscales apart from external
      validity (KR-20: 0.54). Test-retest (r 0.88) and inter-rater (r 0.75) reliability
      of the Quality Index were good. Reliability of the subscales varied from good
      (bias) to poor (external validity). The Quality Index correlated highly with an
      existing, established instrument for assessing randomised studies (r 0.90). There
      was little difference between its performance with non-randomised and with
      randomised studies. Raters took about 20 minutes to assess each paper (range 10
      to 45 minutes). CONCLUSIONS: This study has shown that it is feasible to develop
      a checklist that can be used to assess the methodological quality not only of
      randomised controlled trials but also non-randomised studies. It has also shown
      that it is possible to produce a checklist that provides a profile of the paper,
      alerting reviewers to its particular methodological strengths and weaknesses.
      Further work is required to improve the checklist and the training of raters in
      the assessment of external validity.

PMID- 9764260
TI  - Maternal and infant health problems after normal childbirth: a randomised
      controlled study in Zambia.
AB  - STUDY OBJECTIVES: The main aim of the study was to discover if a midwife home
      visiting programme has a significant effect on the prevalence of health problems
      and breast feeding behaviour of mothers who delivered normally and their healthy
      fullterm newborn babies, during a period of 42 days after delivery. Another aim
      was to compare the mothers', the midwife's, and the doctor's findings of
      prevalence of health problems at the end of the puerperium period. DESIGN: A
      randomised controlled trial was carried out. One group of mothers and their
      infants were randomly allocated to a home visiting group (Group A); the other
      group (Group B) was only visited at day 42. SETTING: The study was carried out at
      the University Teaching Hospital (UTH) in Lusaka, the capital city of Zambia.
      PARTICIPANTS: A total of 408 mothers who had a normal delivery and gave birth to
      a healthy fullterm infant, as assessed by the attending midwife, were randomised
      to two groups. Group A consisted of 208 mother/infant dyads who were visited by a
      midwife in their homes at days 3, 7, 28, and 42 after delivery and Group B
      consisted of 200 mother/infant dyads who were only visited at day 42. MAIN
      RESULTS: At day 42 an equal proportion (30%) of mothers in both groups perceived
      that they had health problems. The prevalence of infant health problems in Group
      B was significantly higher (p < 0.01) as perceived by mothers. There were more
      mothers in Group B (p < 0.01) perceiving insufficient milk production and giving
      supplementary feeding. At day 42, mothers in Group A (56%) took more actions than
      mothers in Group B (41%) to solve infant health problems (p < 0.03). In both
      groups the mothers' perceived own health problems, were significantly higher (p <
      0.01) than those observed by the obstetrician and those observed by the midwife.
      The midwife found more infant health problems in Group B (p < 0.01) than in Group
      A and more infants with health problems in both groups compared with the
      paediatrician's findings (p < 0.01). CONCLUSIONS: There was a significant
      difference between the mothers' reported health problems and the health problems
      identified by the midwife and the doctors. The study shows that a midwife home
      visit and individual health education to mothers, reduce the prevalence of infant
      health problems, and enables the mother to more often take action when an infant
      health problem is identified. There is a need to re-evaluate the midwifery
      training curriculums with the intention to include more infant management care.

PMID- 9764261
TI  - Major incidents in Britain over the past 28 years: the case for the centralised
      reporting of major incidents.
AB  - STUDY OBJECTIVES: To describe the incidence and epidemiology of major incidents
      occurring in Britain over the past 28 years. METHODS: Major incidents were
      identified through a MEDLINE search, a hand search of journals and government
      reports at the Home Office Emergency Planning College, newspaper reports, a
      postal survey of ambulance emergency planning officers, and through requests for
      information posted on the internet. MAIN RESULTS: Brief incidents profiles from
      108 British major incidents are presented. Most major incidents pass unreported
      in the medical literature. On average three to four major incidents occur in
      Britain each year (range 0-11). Sixty three of 108 (59.2%) of incidents involve
      public transportation. The next two largest groups are civil disturbance 22 of
      108 (20.3%) and industrial accidents 16 of 108 (14.8%). Although incidents at
      sports stadiums are rare they produce large numbers of casualties. The data
      currently available on major incidents are difficult to find and of questionable
      accuracy. CONCLUSIONS: The lack of data makes planning for major incidents and
      exercising major incident plans difficult. Casualty incident profiles (CIPs) may
      assist major incidents exercises and planning. CIPs from future major incidents
      should be collated and made available to all major incident planners.

PMID- 9764262
TI  - Individual social class, area-based deprivation, cardiovascular disease risk
      factors, and mortality: the Renfrew and Paisley Study.
AB  - OBJECTIVE: To investigate the associations of individual and area-based
      socioeconomic indicators with cardiovascular disease risk factors and mortality.
      DESIGN: Prospective study. SETTING: The towns of Renfrew and Paisley in the west
      of Scotland. PARTICIPANTS: 6961 men and 7991 women included in a population-based
      cardiovascular disease screening study between 1972 and 1976. MAIN OUTCOME
      MEASURES: Cardiovascular disease risk factors and cardiorespiratory morbidity at
      the time of screening: 15 year mortality from all causes and cardiovascular
      disease. RESULTS: Both the area-based deprivation indicator and individual social
      class were associated with generally less favourable profiles of cardiovascular
      disease risk factors at the time of the baseline screening examinations. The
      exception was plasma cholesterol concentration, which was lower for men and women
      in manual social class groups. Independent contributions of area-based
      deprivation and individual social class were generally seen with respect to risk
      factors and morbidity. All cause and cardiovascular disease mortality rates were
      both inversely associated with socioeconomic position whether indexed by area
      based deprivation or social class. The area-based and individual socioeconomic
      indicators made independent contributions to mortality risk. CONCLUSIONS:
      Individually assigned and area-based socioeconomic indicators make independent
      contributions to several important health outcomes. The degree of inequalities in
      health that exist will not be demonstrated in studies using only one category of
      indicator. Similarly, adjustment for confounding by socioeconomic position in
      aetiological epidemiological studies will be inadequate if only one level of
      indicator is used. Policies aimed at reducing socioeconomic differentials in
      health should pay attention to the characteristics of the areas in which people
      live as well as the characteristics of the people who live in these areas.

PMID- 9764263
TI  - Participation of French general practitioners in public health surveillance: a
      multidisciplinary approach.
AB  - STUDY OBJECTIVES: To evaluate the feasibility of a novel approach to measure
      compliance of sentinel general practitioners (SGPs) in sentinel public health
      surveillance and to determine the characteristics in the SGP's profile that can
      be objectively associated with their perseverance in public health surveillance.
      DESIGN: Prospective study of the compliance of the SGPs (compliance being defined
      as the length of time during which an SGP complies with a given theoretical
      surveillance protocol) and qualitative study of the determinants of their initial
      motivations (using group and face to face interviews). SETTING: The 1970 SGPs who
      have participated in the Sentinel system since 1984. PARTICIPANTS: Among them,
      the 502 SGPs recruited since 1 July 1992 have been questioned by mailed
      questionnaire and 20 SGPs have been questioned during face to face semistructured
      interviews. MAIN RESULTS: According to the maximum number of silences allowed by
      the given theoretical protocol, median compliances varied between 1.9 months (95%
      CI = (1.8, 2.0)) and 14.3 months (95% CI = (13.8, 15.2)). In multivariate
      analysis, long compliances for SGPs with a < or = 5 or > or = 20 years seniority
      was seen and an interest in using multimedia home servers. On the other hand,
      interest in local epidemiological surveys and previous experience with other
      surveillance networks or clinical trials were associated with short compliances.
      No statistical association was found between compliance and computing experience,
      having a medical secretary, a particular feeling of being a "public health
      actor", or the desire to belong to a GPs' network. A thematic analysis of
      interview records showed that the main motivation of the SGPs was their need to
      share their experiences and to self evaluate by comparison with colleagues by the
      means of a surveillance system that would be used as a health information system.
      CONCLUSIONS: The longitudinal method used in this study was shown to be an
      efficient tool to monitor non-compliant SGPs with respect to given surveillance
      protocols. Furthermore, this approach allows the selection out of the SGPs'
      profile the characteristics that are associated with a longer compliance. The
      additional variables to be taken into account in this profile could be identified
      among the topics, attitudes, and experiences collected during the semistructured
      interviews. This work considers the question of understanding what determines the
      motivation of GPs to participate in public health surveillance and what are their
      expectations of feed back. This question is essential if information systems in
      general practice are to be implemented.

PMID- 9764264
TI  - Control group characteristics and study outcomes: empirical data from a study on
      mortality of patients with type 2 diabetes mellitus in Dutch general practice.
AB  - STUDY OBJECTIVE: Control group characteristics as comorbidity and chronic
      psychosocial problems may play an important part in study outcomes. A primary
      care data base was used to quantify the effects of varying the case mix of
      participants. DESIGN: Historical cohort study. SETTING: Data were collected from
      1967-1996 in four Dutch general practices performing the Continuous Morbidity
      Registration Nijmegen. PATIENTS AND CONTROLS: All newly diagnosed type 2 diabetic
      patients in the period 1967-1989 fulfilling the WHO criteria (n = 265); for each
      type 2 diabetic patient a control was matched for practice, sex, age, and social
      class; from these controls subgroups were selected based on the absence of
      different types of morbidity; these subgroups were also matched for practice,
      sex, age, and social class. MAIN RESULTS: The relative risk of mortality in type
      2 diabetic patients in comparison with various subsets of controls ranged from
      1.33 (95% CI 0.97, 1.81) to 2.16 (95% CI 1.46, 3.20). CONCLUSION: Control group
      characteristics as comorbidity and chronic psychosocial problems turned out to
      influence the risk estimation in a cohort study. General practice data enhance
      the study of these aspects.

PMID- 9764265
TI  - Approaches to the denominator in practice-based epidemiology: a critical
      overview.
AB  - OBJECTIVES: An accurate knowledge of the population at risk is a fundamental
      requirement for determining rates and making comparisons in epidemiological
      research. The major obstacle of studying the epidemiology of sentinel practice
      networks is the determination of population at risk, in this case, the reference
      population of medical practices. This article is intended to give a brief
      overview of major denominator approaches used in practice based epidemiology
      today, to discuss their underlying assumptions, their strengths and limitations.
      DESIGN: The literature used in this paper was searched from Medline databases of
      1970-1997 using the logical expression "denominator and practice". More
      literature was identified from the references cited in those articles and from
      research reports that were available to the authors. MAIN RESULTS: There are
      various approaches to the denominator at different levels of complexity, which
      were presented akin to the well known "iceberg phenomenon": with only a small
      portion of the iceberg visible above the surface, inference as to the size of the
      invisible part may still be made under certain assumptions. Crude numbers of
      cases may still reflect trends in the true epidemiology of disease and may be
      useful for time-series analyses. Differences in the number of network
      participants over time and across region may be controlled for by using the
      number of sentinel practices as a denominator. The number of consultations is a
      first step towards a population-based denominator, reflecting characteristics of
      both patients and the network. The yearly or quarterly contact group is a true
      person-based denominator, yet disregarding the population not consulting. The
      population in practices' catchment areas can be either determined from patient
      lists or estimated using mathematical models. The ideal denominator is the total
      population in a geographically defined area, though this information can be
      directly related to medical practices only in very few countries. CONCLUSIONS:
      Although a person, or ideally a population-based denominator is desirable, even
      "lower-level" denominators may be suitable for certain research topics. In
      countries without patient registration, the estimation of incidences and
      prevalences has many methodological uncertainties that limit the use of sentinel
      practice systems. Assuming representativeness, valid analytical or time-series
      studies, however, can still be carried out even if there is very little
      information on the population at risk covered by particular medical practices.

PMID- 9764266
TI  - Audit of populations in general practice: the creation of a national resource for
      the study of morbidity in Scottish general practice.
AB  - STUDY OBJECTIVE: To create a national data resource for studying morbidity in
      Scottish general practice, complementary to existing information systems and
      available for management and research purposes at national and local levels.
      DESIGN: The Department of General Practice, University of Aberdeen has worked
      since 1988 to collect and analyse computerised information at practice, regional,
      and national levels by distribution of a floppy disk-based software program,
      which extracts a predetermined dataset from each general practice computer
      system. SETTING: Almost 100% of patients in Scotland are registered with a
      general practitioner. Scotland has a national computer system, General Practice
      Administration System for Scotland (GPASS), used by over 75% of all Scottish
      practices. Escalating costs of health care and demographic changes in the
      national population emphasise the monetary value of the gatekeeper role of
      general medical practice. General practitioners' increasing involvement in the
      provision and purchasing of care has raised the importance of the management of
      populations as well as the care of individual patients. PATIENTS: Collection of
      major morbidity and prescribing data from up to 2.4 million patients,
      approximately half the population of Scotland, takes place biannually. A subset
      of practices (population 282,700 patients; 52 practices) are continuously
      collecting doctor/patient contact information (symptoms or diagnoses). MAIN
      RESULTS: The data collected provide information at the level of the individual
      patient. Morbidity, prescribing, screening, and administrative data can be linked
      by patient, date or postcode. The sample population studied is representative by
      age, sex, deprivation, and sparsity (using the postcode) of the national
      population. Large sub-populations of patients satisfying a selected criteria can
      be extracted for further study of needs assessment or of epidemiological
      research. CONCLUSIONS: The gatekeeping role of Scottish general practice and the
      predominance of GPASS favours standardisation of methods of data capture and the
      construction of large regional, national, and Continuous Morbidity databases.
      Analysis by geographical, demographic, and temporal distributions allows the
      changing patterns of illness and provision of health care to be studied in
      substantial detail to the benefit of patients, doctors, and the national health
      service.

PMID- 9764267
TI  - Anonymous unlinked testing as a sentinel approach: experience in Germany.
AB  - STUDY OBJECTIVE: To establish a laboratory sentinel as a supplementary instrument
      for monitoring the seroprevalence of HIV among childbearing women as a proxy to
      the heterosexually active population. DESIGN/SETTING: Anonymous unlinked testing
      of neonatal dried blood spots has been performed in central laboratories of three
      federal states since 1993. The survey uses residual dried blood spots collected
      on Guthrie cards for screening of infants for metabolic disorders. These are
      eluted and tested for HIV antibodies. Data retained with the specimen are only
      district of residence along with year and month of birth. PARTICIPANTS: Because
      maternal IgG crosses the placenta before birth, the presence of antibodies in
      newborns reflects the infection status of the mother. Childbearing women are
      fairly representative for the heterosexually active general population. MAIN
      RESULTS: The observed HIV prevalence in childbearing women of less than 1 per
      thousand confirms the assumption of a low rate of HIV infection in the general
      population. Significant time trends could not be detected, but HIV prevalence was
      higher in metropolitan compared with rural areas. CONCLUSIONS: Laboratory
      sentinels in general and the anonymous unlinked testing of neonatal dried blood
      spots in particular can supply additional information on HIV seroprevalence. This
      surveillance system could be expanded to utilise residual samples of other
      sources as well as to monitor the immunity against specific vaccine preventable
      diseases and other infectious diseases of public health relevance.

PMID- 9764268
TI  - Surveillance of influenza in Wales: interpreting sentinel general practice rates
      using contemporaneous laboratory data. Opportunities and limitations.
AB  - OBJECTIVES: To evaluate the opportunities and limitations of using laboratory
      data to enhance sentinel general practice surveillance of influenza. DESIGN:
      Descriptive study of active sentinel surveillance of clinically diagnosed
      influenza in general practice and passive total population surveillance of
      laboratory reports of influenza A, influenza B, Mycoplasma pneumoniae, and
      respiratory syncitial virus infections. SETTING: Wales. SUBJECTS: Total sentinel
      practices population (currently 228,130); population of Wales (2,913,000, 1994
      mid-year estimate). MAIN OUTCOME MEASURES: Simplicity, flexibility,
      acceptability, sensitivity, predictive value positive, representativeness, and
      timeliness of a surveillance system. Rate of influenza and other respiratory
      infections. RESULTS: Sentinel general practice surveillance of influenza in Wales
      is simple, flexible, acceptable, timely, representative, and relatively
      sensitive. Current laboratory surveillance is complex and less timely than
      sentinel practice surveillance but is complete and has a relatively high positive
      predictive value. For the period January 1993 to September 1996, peaks in rates
      of influenza reported by sentinel practices during winters 1993/94 and 1995/96
      were temporally associated with increased rates of laboratory confirmed influenza
      A and respiratory syncitial virus, whereas the peak in 1994/95 was associated
      with increased rates of laboratory confirmed influenza B, M pneumoniae, and
      respiratory syncitial virus. CONCLUSIONS: Timely laboratory data can add value to
      influenza data already obtained from sentinel general practice surveillance.
      However continuous audit is essential to resolve the possible limitations of
      either surveillance system.

PMID- 9764270
TI  - Programme for the surveillance of influenza in Portugal: results of the period
      1990-1996.
AB  - OBJECTIVES: To describe the situation of the influenza in Portugal through the
      estimates of the incidence rates and the identification of the viral strains
      implicated on it during the period 1990-1996. DESIGN: The integrated clinical and
      laboratory surveillance system for influenza in Portugal is based on the
      Portuguese sentinel network. Influenza cases are identified by general
      practitioners (GP) and notified to Division of Epidemiology (DEP) and to National
      Influenza Centre. Clinical and epidemiological data based on the clinical
      diagnosis are recorded and incidence rates are computed for the whole country.
      Throat swabs and blood samples are taken from the patients with influenza and
      sent to the National Influenza Centre to identify and classify the viral strains
      implicated. PARTICIPANTS: Lists of patients of the GPs collaborating on "Medicos
      Sentinela" network. RESULTS: In 1990-1991, 1992-1993, and 1994-1995 there was a
      higher prevalence of influenza B virus and the highest influenza activity
      occurred in February and March in contrast with 1991-1992, 1993-1994, and 1995
      1996 where the highest numbers of influenza cases occurred in November and
      December, and were associated with influenza A. CONCLUSIONS: During the past six
      years, 1990-1996, the influenza activity has been moderate in Portugal. From 1990
      1996 influenza A and B viruses were prevalent every second year. The prevalence
      of influenza A was associated with the occurrence of the highest number of
      influenza cases during December and January and the prevalence of influenza B
      with the occurrence of the highest number of influenza cases during February and
      March.

PMID- 9764269
TI  - Surveillance of influenza-like illness in France. The example of the 1995/1996
      epidemic.
AB  - STUDY OBJECTIVES: To discover if continuous computerised collection of morbidity
      data through a medical practice based sentinel network can be used to monitor
      influenza-like illness (ILI) epidemics. To obtain rough estimates of influenza
      vaccine effectiveness. DESIGN: Continuous passive surveillance of ILI through a
      computerised network of voluntary sentinel general practitioners (SGPs) in France
      (Sentinelle system). SETTING: Five hundred SGPs practices. PARTICIPANTS: Since
      1984, SGPs updated a database with information on eight communicable diseases
      including ILI, via videotext terminals. Each ILI case is defined by the
      association of a sudden fever of 39 degrees C or above, respiratory symptoms, and
      myalgias. An ILI epidemic is detected when the national weekly incidence rate
      exceeds a seasonal threshold for two successive weeks. MAIN RESULTS: An ILI
      epidemic was reported from November 1995 to January 1996. In total, 13,951
      individual cases were reported by SGPs during the epidemic period. The size of
      the epidemic (number of patients consulting a GP) was estimated to be 2,370,000
      subjects. Maps of the epidemic showed that all regions have reported a high level
      ILI activity. The attack rate was the highest in school age children (13.5/100)
      and decreased as the age rose. Nearly 6% of the reported ILI cases among adults
      and elderly were vaccinated. The flu vaccine effectiveness against ILI was
      estimated to be 66% (95% CI 73%, 92%), ranging between 83% (95% CI 73%, 92%)
      among the subjects aged 15 to 24 years old to 16% (95% CI -12%, 44%) among the
      subjects aged 75 years or older. CONCLUSIONS: The Sentinelle system demonstrated
      adequate sensitivity and timeliness regarding ILI epidemic. Moreover, results of
      the monitoring were made available on the internet to increase the dissemination
      of information. Also, estimates of influenza vaccine effectiveness have been
      easily obtained. Altogether, they represent key points for the control of crisis
      situation such as ILI epidemics or pandemics.

PMID- 9764271
TI  - A study of reasons for an increase in acute respiratory tract infections reported
      by influenza sentinel practices in Germany.
AB  - The influenza sentinel and early warning system of the working group on influenza
      (AGI) comprises more than 600 general practitioners and paediatricians
      nationwide. The observations made by national influenza monitoring systems rely
      on parameters that differ between countries. The definition of the numerators and
      denominators used depends to an important extent on the national health care
      systems, and considerable differences between the national monitoring systems
      have to be expected. Consequently the validity and reliability of recorded data
      as well as the indicative value of certain observations have to be checked for
      each system. The reasons for an increase in acute respiratory infections relative
      to total practice contacts, as well as the number of persons who are unable to
      work, were investigated by telephone interviews with the reporting physicians.
      Reasons for such increases given by the physician included increases in morbidity
      in the population but to a considerable extent "organisational" reasons, not
      linked to an increase in morbidity were identified. Many of those
      "organisational" reasons seemed to be relevant in health care systems that allow
      the patients a free choice of the contacted physician. The telephone interview
      was helpful for interpretation of the data and the detection of primary local
      outbreaks.

PMID- 9764272
TI  - Epidemiology of chickenpox in France (1991-1995).
AB  - STUDY OBJECTIVES: To decide whether a mass immunisation against chickenpox should
      be or should not be organised, it is important to have up to date data on the
      disease and to have baseline data to further assess a mass immunisation strategy,
      if any. DESIGN: Recent chickenpox epidemiology (age and sex distribution,
      seasonal dynamic and complications) in France are reviewed. SETTING: The system
      works with about 500 Sentinelle general practitioners (SGPs) and has provided
      surveillance of frequent communicable diseases in continental France since 1984.
      PARTICIPANTS: The data were collected by the computerised Sentinelle system. The
      Sentinelle system uses a videotex server that allows information exchange, data
      entry, and synthetic return of information. Chickenpox was defined as a sudden
      onset of typical skin eruption with pruritus, leaving scabs and associated with
      moderate fever. For each reported case, the SGP gave information on the age of
      the patient, sex, prevailing childcare for the children, contacts and
      complications (skin superinfections, lower and upper respiratory infections,
      conjunctivitis and corneal infections, nervous system injuries, stomatitis and
      others). Spectral analysis was used to detect cyclical patterns. MAIN RESULTS:
      Between 1991 and 1995, 15,817 cases of chickenpox were reported and provided the
      basis for the analysis. The yearly national incidence was 1.0-1.35 cases per 100
      inhabitants. A pronounced annual periodicity of the incidence was observed and
      confirmed by spectral analysis. Ninety two per cent of chickenpox cases occurred
      in children under 14 years of age with about 5% being under one. Complications
      were reported in 2% of the cases. Common complications reported were skin
      superinfections, lower and upper respiratory tract infections. However, 21 cases
      out of 318 complications were nervous system injuries including six encephalitis
      or cerebellar ataxia. All these cases recovered completely. CONCLUSIONS:
      Chickenpox is usually a benign childhood disease. This study affords up to date
      observations on the disease in France. A large panel of complications has been
      reported. This paper provides the first attempt to describe the epidemiology of
      chickenpox in France.

PMID- 9764273
TI  - Contamination of human breast milk with organochlorine residues: a comparison
      between East and West Germany through sentinel practice networks.
AB  - STUDY OBJECTIVE: The aim of the study was to assess and compare the contamination
      of human breast milk with organochlorine residues through two sentinel practice
      networks in Lower Saxony, a state of former West Germany, and Saxony-Anhalt, a
      state of former East Germany. DESIGN: Eligible women were enrolled in this cross
      sectional study by a network of 51 paediatric practices in Lower Saxony and 44 in
      Saxony-Anhalt when bringing their babies for a regular screening examination four
      to six weeks after delivery. Sociodemographic, lifestyle, and exposure factors
      were determined by questionnaire. Milk samples were analysed for
      hexachlorocyclohexane (HCH), hexachlorbenzole (HCB), DDT, dieldrin,
      polychlorinated biphenyls (PCB), and heptachlorepoxid (HCE); half the samples
      were also analysed for dioxin. Analytic statistics were computed using multiple
      logistic regression. SETTING: The study was conducted in Lower Saxony, Germany,
      from July 1992 to June 1993, and in Saxony-Anhalt, Germany, from January to June
      1995. PARTICIPANTS: 156 primiparous, breast-feeding women from Lower Saxony and
      113 from Saxony-Anhalt were studied, who either were born and raised in former
      West or East Germany, respectively. MAIN RESULT: Mean age of mothers and children
      differed significantly between the two study groups. In Lower Saxony all but two
      milk samples were well below the tolerable concentrations established by the
      German Research Council (Deutsche Forschungsgemeinschaft (DFG)). In Saxony-Anhalt
      no participant had concentrations above those recommended by the DFG. After
      adjustment for age of mother and child, occupational and non-occupational
      pesticide contact, DDT and beta-HCH concentrations were significantly lower in
      Lower Saxony; HCE and dieldrin concentrations were lower in Saxony-Anhalt. No
      differences between the two states were found for PCB, HCB, gamma-HCH, and
      dioxin. CONCLUSIONS: Breast milk contamination levels in former East German
      Saxony-Anhalt exceeded the contamination in Lower Saxony only for DDT and beta
      HCH.

PMID- 9764275
TI  - Public health: where should we be in 10 years?

PMID- 9764274
TI  - Sentinel practices in evaluating longer periods of care: quality of life and drug
      therapy of terminally ill persons in Lower Saxony (Germany).
AB  - STUDY OBJECTIVES: (1) To study the feasibility of using sentinel practice
      networks to evaluate longer periods of care. (2) To assess the quality of life
      and drug therapy of community dwelling terminally ill persons. DESIGN:
      Prospective longitudinal design with GPs in an existing sentinel practice network
      identifying "terminally ill" persons and recording the following data: age, sex,
      diagnoses, and ongoing drug therapy initially, time, place, duration, services,
      and drug changes for every contact, quality of life (HRCA-QL Index, Spitzer
      Index, uniscale), pain intensity and frequency on a weekly basis, and time and
      circumstances of death. SETTING: 26 GP practices in Lower Saxony, Germany.
      PATIENTS: 47 patients (age: mean 76 years, range 31 to 98; sex: 21 male, 26
      female; diagnosis: 35 with cancer) with 582 contacts. Mean of recorded time
      before death was 70 days (median 50). MAIN RESULTS: Average number of physician
      patient contacts increased from 0.7 a week three months before death to 2.4 in
      the final week. Quality of life decreased during that period (HRCA-QL Index: 5.1
      to 0.8; Spitzer: 4.4 to 0.8; uniscale: 37 to 9). In the last week of life, no
      person was free of pain; analgetic therapy was "successful" in 57% of cases.
      CONCLUSIONS: (1) The sentinel practice approach is feasible for evaluating longer
      periods of care. The generalisibility, however, may be limited to certain
      subgroups. (2) The observed trends in quality of life, pain, and analgetic
      treatment should be compared with those in other settings and countries to
      identify the scope of care improvement.

PMID- 9764276
TI  - An excess of tetralogy of Fallot in Malta.
AB  - STUDY OBJECTIVE: To estimate birth prevalence of tetralogy of Fallot (TF) in
      Malta. DESIGN: Retrospective data collection and analysis, and comparison with
      earlier epidemiological studies dealing with congenital heart disease. SETTING:
      Regional hospital providing exclusive diagnostic and follow up services for the
      entire country of Malta. PATIENTS: All Maltese live births diagnosed as having
      TF. MAIN RESULTS: The birth prevalence of TF in Malta for the period 1980-1994
      was 0.64/1000 live births (95% confidence intervals 0.48, 0.85/1000 live births).
      This was significantly higher than previously reported in the medical literature.
      CONCLUSIONS: The Maltese gene pool seems to have a genetic predisposition towards
      live births with TF. Population genetic studies with emphasis on the prevalence
      of 22q11 microdeletion may yield clues regarding the cause of the high rate of
      this condition.

PMID- 9764277
TI  - Relation between locomotion impairment, functional independence in retirement,
      and occupational strain resulting from work carried out during working life.
      Study of a sample population of 350 miners in the Loire valley in France.
AB  - STUDY OBJECTIVES: To analyse long term effects of working conditions experienced
      at an advanced age, and after retirement by quantifying occupational strain,
      impairment, and disability to establish their interrelation. DESIGN:
      Retrospective study. PARTICIPANTS: Retired miners from The French Coal Board who
      had worked in the coal fields of the Loire valley. From a potential population of
      507 retired miners, 350 were completely evaluated. MEASUREMENT: The study
      examines the occupational strain experienced by each subject, measured using both
      auto-evaluation and evaluation by experts and the locomotion impairment and the
      functional independence. MAIN RESULTS: A significant relation between the
      evaluation of occupational strain and functional independence and locomotion
      impairment of the low back was found and also a significant relation between
      locomotion impairment of the low back and the length of time spent working at the
      coal face. CONCLUSIONS: This study confirms other studies as regards the effects
      of occupation on health status and on the aging process, but it goes further to
      show the consequences of this relation on functional independence.

PMID- 9764278
TI  - Underregistration of neonatal deaths: an empirical study of the accuracy of
      infantile vital statistics in Taiwan.
AB  - STUDY OBJECTIVE: The accuracy of the official statistic on infant deaths in
      Taiwan has been questioned. This study aimed to survey infant deaths nationwide,
      to measure associated vital statistics, and compare them with the official
      statistics to assess accuracy. DESIGN AND PARTICIPANTS: A nationwide survey of
      all gestational outcomes occurring at > or = 20 weeks' gestation over a three day
      study period (15-17 May 1989) was conducted to collect data from 23 counties and
      cities nationwide using a two stage data collection procedure. MAIN RESULTS: The
      survey derived infant death rate was 9.72 per 1000 live births, which was higher
      than the reported official statistic of 5.71 per 1000 live births. A more
      detailed examination of data on infant deaths showed that the estimated neonatal
      death rate of 6.68 per 1000 live births (95% confidence intervals: 3.33, 11.96
      per 1000 live births) was significantly higher than the published official
      statistic of 1.94 per 1000 live births, while the postneonatal mortality of 3.04
      per 1000 live births was comparable to the reported statistic of 3.37 per 1000
      live births. CONCLUSIONS: This study empirically documented the underregistration
      of infant deaths in Taiwan, particularly those occurring during the first 27 days
      of life.

PMID- 9764279
TI  - Socio-cultural factors in maternal morbidity and mortality: a study of a semi
      urban community in southern Nigeria.
AB  - STUDY OBJECTIVE: To understand community based or socio-cultural factors that
      determine maternal morbidity and mortality in a semi-urban setting. DESIGN: The
      study is an exploratory multidisciplinary operations research and the instruments
      were focus groups and interviews. SETTING: Ekpoma, a semi-urban community with a
      population of 70,000 in central part of Edo state in southern Nigeria.
      PARTICIPANTS: Thirteen groups of women, two groups of men, and two groups of
      traditional birth attendants. RESULTS: There is a fairly good knowledge of
      haemorrhage but this is circumscibed by attitudes, practices, and situations that
      keep women away from or delay the decision to seek modern obstetric care.
      CONCLUSIONS: For a fuller understanding of maternal morbidity and mortality, it
      is important to consider factors outside the hospital and formal medical
      practice. Furthermore, a change of existing knowledge, attitudes, practices, and
      situations can be enhanced through modelling on them.

PMID- 9764280
TI  - Reported health, lifestyles, and use of health care of first generation
      immigrants in The Netherlands: do socioeconomic factors explain their adverse
      position?
AB  - OBJECTIVE: Differences in health, lifestyles, and use of health care between
      groups of varying ethnic origin can have important implications for preventive
      and curative health care. This paper studies whether socioeconomic factors
      explain ethnic differences in these outcomes. DESIGN: Data on health status,
      lifestyles, and use of health care were obtained from interviews with 3296 people
      aged 16-64 years (response: 60.6%), among whom were 848 first generation
      immigrants. Ethnic differences in these outcomes were examined with and without
      adjustment for socioeconomic factors, using logistic regression. SETTING: General
      population of Amsterdam, the Netherlands. MAIN OUTCOME MEASURES: Health status
      (self rated health, General Health Questionnaire, functional limitations),
      lifestyles (smoking, alcohol), and use of health care (general practice,
      pharmaceuticals, hospitalisations). MAIN RESULTS: Immigrants from Turkey, Morocco
      and (former) Dutch colonies report a poorer health and a higher use of health
      care, especially primary health care among the elderly. An adverse socioeconomic
      position partially explains the poor health of these immigrants. In turn, their
      poor health explains most of their higher use of health care. CONCLUSIONS:
      Cultural factors and poor living conditions seem to contribute to the poor health
      of immigrants, besides an adverse socioeconomic position. The pressure on various
      health services will increase in future because of the relatively high increase
      in immigrants' needs at older ages and their presently low mean age.

PMID- 9764281
TI  - Testing for Helicobacter pylori in primary care: trouble in store?
AB  - STUDY OBJECTIVE: To assess the role of testing for Helicobacter pylori in the
      management of dyspeptic patients in primary care. DESIGN: Selective review of
      literature frequently quoted to support use of H pylori testing. MAIN RESULTS:
      Testing for H pylori and referral of only positive cases for endoscopy aims to
      reduce the number of "unnecessary" endoscopies. Patients with negative results
      may receive short-term reassurance and subsequently place fewer demands on health
      services. However, studies to date have only assessed this practice in secondary
      care settings. Given the relatively high prevalence of both dyspepsia and H
      pylori infection, the transfer of this practice to primary care may lead to a
      paradoxical increase in endoscopy referrals. Identification of H pylori and
      prescribing of eradication treatment also aims to reduce endoscopy referrals. No
      primary care trials have yet assessed this approach. Given that fewer than one in
      four of dyspeptic patients have peptic ulceration, a high proportion may fail to
      respond to eradication treatment and subsequently require referral for endoscopy.
      The longer term clinical and psychosocial sequelae of treating or labelling
      patients with an infection associated with gastric cancer remain unknown.
      CONCLUSIONS: Given uncertainty concerning the possible adverse effects of H
      pylori testing in primary care, we suggest a moratorium on its use in this
      setting until results from relevant clinical trials become available.

PMID- 9764282
TI  - Midwifery care, social and medical risk factors, and birth outcomes in the USA.
AB  - STUDY OBJECTIVE: To determine if there are significant differences in birth
      outcomes and survival for infants delivered by certified nurse midwives compared
      with those delivered by physicians, and whether these differences, if they exist,
      remain after controlling for sociodemographic and medical risk factors. DESIGN:
      Logistic regression models were used to examine differences between certified
      nurse midwife and physician delivered births in infant, neonatal, and
      postneonatal mortality, and risk of low birthweight after controlling for a
      variety of social and medical risk factors. Ordinary least squares regression
      models were used to examine differences in mean birthweight after controlling for
      the same risk factors. STUDY SETTING: United States. PATIENTS: The study included
      all singleton, vaginal births at 35-43 weeks gestation delivered either by
      physicians or certified nurse midwives in the United States in 1991. MAIN
      RESULTS: After controlling for social and medical risk factors, the risk of
      experiencing an infant death was 19% lower for certified nurse midwife attended
      than for physician attended births, the risk of neonatal mortality was 33% lower,
      and the risk of delivering a low birthweight infant 31% lower. Mean birthweight
      was 37 grams heavier for the certified nurse midwife attended than for physician
      attended births. CONCLUSIONS: National data support the findings of previous
      local studies that certified nurse midwives have excellent birth outcomes. These
      findings are discussed in light of differences between certified nurse midwives
      and physicians in prenatal care and labour and delivery care practices. Certified
      nurse midwives provide a safe and viable alternative to maternity care in the
      United States, particularly for low to moderate risk women.

PMID- 9764283
TI  - Clinical significance not statistical significance: a simple Bayesian alternative
      to p values.
AB  - OBJECTIVES: To take the common "Bayesian" interpretation of conventional
      confidence intervals to its logical conclusion, and hence to derive a simple,
      intuitive way to interpret the results of public health and clinical studies.
      DESIGN AND SETTING: The theoretical basis and practicalities of the approach
      advocated is at first explained and then its use is illustrated by referring to
      the interpretation of a real historical cohort study. The study considered
      compared survival on haemodialysis (HD) with that on continuous ambulatory
      peritoneal dialysis (CAPD) in 389 patients dialysed for end stage renal disease
      in Leicestershire between 1974 and 1985. Careful interpretation of the study was
      essential. This was because although it had relatively low statistical power, it
      represented all of the data that were available at the time and it had to inform
      a critical clinical policy decision: whether or not to continue putting the
      majority of new patients onto CAPD. MEASUREMENTS AND ANALYSIS: Conventional
      confidence intervals are often interpreted using subjective probability. For
      example, 95% confidence intervals are commonly understood to represent a range of
      values within which one may be 95% certain that the true value of whatever one is
      estimating really lies. Such an interpretation is fundamentally incorrect within
      the framework of conventional, frequency-based, statistics. However, it is valid
      as a statement of Bayesian posterior probability, provided that the prior
      distribution that represents pre-existing beliefs is uniform, which means flat,
      on the scale of the main outcome variable. This means that there is a limited
      equivalence between conventional and Bayesian statistics, which can be used to
      draw simple Bayesian style statistical inferences from a standard analysis. The
      advantage of such an approach is that it permits intuitive inferential statements
      to be made that cannot be made within a conventional framework and this can help
      to ensure that logical decisions are taken on the basis of study results. In the
      particular practical example described, this approach is applied in the context
      of an analysis based upon proportional hazards (Cox) regression. MAIN RESULTS AND
      CONCLUSIONS: The approach proposed expresses conclusions in a manner that is
      believed to be a helpful adjunct to more conventional inferential statements. It
      is of greatest value in those situations in which statistical significance may
      bear little relation to clinical significance and a conventional analysis using p
      values is liable to be misleading. Perhaps most importantly, this includes
      circumstances in which an important public health or clinical decision must be
      based upon a study that has unavoidably low statistical power. However, it is
      also useful in situations in which a decision must be based upon a large study
      that indicates that an effect that is highly statistically significant seems too
      small to be of practical relevance. In the illustrative example described, the
      approach helped in making a decision regarding the use of CAPD in Leicestershire
      during the latter half of the 1980s.

PMID- 9764284
TI  - The Short-Form 36 and older people: some problems encountered when using postal
      administration.
AB  - OBJECTIVE: To explore some of the problems encountered in the postal
      administration of the Short-Form 36 (SF-36). Questions that seem to present
      particular difficulties for the group are identified. In addition some of the
      written comments from the questionnaires and people's responses to questions on
      how difficult they found the SF-36 are discussed. DESIGN: The study group were
      asked to complete a health questionnaire containing the SF-36 on three separate
      occasions (at zero, three, and six months). The first and final questionnaires
      were interviewer administered during a face to face interview. A shorter
      questionnaire containing only the SF-36 and another health status measure was
      sent by post to each patient in the interim. PARTICIPANTS: People aged 65 years
      or above who were new referrals to community based occupational therapy or
      physiotherapy services in three areas in north west England. MAIN RESULTS:
      Response and completion rates for the postal questionnaire were lower than
      expected, even though all the patients had already had a face to face interview
      and had therefore completed the SF-36 once. Only 34 of 56 respondents (60.7%)
      completed all the items on the SF-36. CONCLUSIONS: All those planning to use the
      SF-36 (and similar measures) with older populations should be sensitive to the
      problems of postal administration. Non-return of questionnaires, high levels of
      missing data on those that are received, and ambiguities in response may mean
      that other measures, or perhaps alternative research methods, are more
      appropriate.

PMID- 9764285
TI  - Evaluation by Markov chain models of a non-randomised breast cancer screening
      programme in women aged under 50 years in Sweden.
AB  - STUDY OBJECTIVE: To apply Markov chain models that have previously been used on
      data in randomised trials of breast cancer screening to data from an uncontrolled
      service screening programme; to compare results with those from a randomised
      trial. DESIGN: A service screening programme in Uppsala county, Sweden, inviting
      25,660 women aged 39-49 to mammographic screening every 20 months, and the
      Swedish Two-County Trial inviting 19,844 women aged 40-49 to two yearly
      screening, compared with 15,604 women of the same age in an unscreened control
      group. Data were analysed using Markov chain models and quasi-likelihood
      estimation procedures. MAIN RESULTS: The results with respect to parameters of
      disease progression were very similar between the two studies. Use of estimated
      progression rates to predict the effect on mortality ranged from a 10% to a 17%
      reduction in breast cancer mortality in the Two-County Study and predicted a 15%
      reduction in the Uppsala programme. These compare well with the observed
      mortality reduction of 13% in the Two-County Trial. CONCLUSIONS: The screening in
      the Uppsala programme is likely to have a similar effect to that observed in the
      Two-County Trial. It is feasible to evaluate non-randomised service screening
      programmes using Markov chain models.

PMID- 9764286
TI  - What's not in a name. The accuracy of using names to ascribe religious and
      geographical origin in a British population.

PMID- 9764287
TI  - How ordinary people in Great Britain perceive the health risks of smoking.

PMID- 9764288
TI  - Dose classification.

PMID- 9764289
TI  - The molecular genetics of inherited deafness--current and future applications.

PMID- 9764290
TI  - How long should ears be bandaged after otoplasty?
AB  - A firm head dressing is usually applied after otoplasty. Some surgeons recommend
      that the patient should wear the bandage for up to 10 days after surgery.
      However, these bandages are frequently displaced or come off. Patients complain
      of reduced hearing, itch and the smell of old blood in the bandages. A case
      series of 52 patients undergoing bilateral otoplasty who had a head bandage on
      for only 24 hours was audited prospectively. Minor complications occurred in two
      patients. A head bandage does not need to remain on for more than 24 hours after
      otoplasty.

PMID- 9764291
TI  - Cochlear implantation under local anaesthesia, the Belfast experience.
AB  - The profoundly deaf, who gain little or no benefit from conventional hearing aids
      and meet various criteria are potential candidates for cochlear implantation. The
      last two decades have witnessed remarkable progress in this field, and it is now
      a routine clinical procedure. A few adult patients who are potential candidates
      for cochlear implantation have an unacceptably high risk for hypotensive general
      anaesthesia due to other systemic conditions. This group has been successfully
      implanted under local anaesthesia in our centre. The post-implantation progress
      of these patients was comparable to those carried out under hypotensive general
      anaesthesia. Data regarding patient selection criteria, examination, anaesthesia,
      surgery and the outcome are discussed. It was concluded that cochlear
      implantation under local anaesthesia is a safe and effective procedure for those
      patients who otherwise may be denied an implant.

PMID- 9764293
TI  - Closure of the nasal vestibule in atrophic rhinitis--a new non-surgical
      technique.
AB  - A new technique is described for closing the nasal vestibule in cases of
      secondarily-acquired atrophic rhinitis. This involves occlusion of the nasal
      vestibule with an obturator made from dimethylpolysiloxane. Being a non-invasive
      method it is specifically indicated in the management of cases of secondarily
      acquired atrophic rhinitis where any surgical treatment is contra-indicated. We
      describe its use in a case each of unilateral and bilateral secondary atrophic
      rhinitis.

PMID- 9764292
TI  - Stability measurements of craniofacial implants by means of resonance frequency
      analysis. A clinical pilot study.
AB  - Nineteen patients previously treated with 52 implants for anchorage of
      craniofacial prostheses were subjected to implant stability measurements by means
      of resonance frequency analysis (RFA), six months to 15 years after implant
      placement. The resonance frequency (RF) of a transducer attached to the implant
      abutment was measured by using a frequency response analyser, a personal computer
      (PC) and dedicated software. Statistically significant higher RF values were seen
      for implants in the temporal bone as compared to implants in the nose and
      periorbital regions. There was a positive correlation with time since implant
      placement for the period from six months up to seven years. It was concluded that
      the preliminary results suggest that implant stability increases with time and
      that implants in temporal bone are more stable than implants in the bone in the
      nose and periorbital regions, probably reflecting differences in bone density.

PMID- 9764294
TI  - The 'swing-door' technique for uncinectomy in endoscopic sinus surgery.
AB  - Uncinectomy is an important step in endoscopic sinus surgery. The traditional
      method of performing uncinectomy has the risk of penetration of the lamina
      papyracea with orbital fat exposure. If the orbital penetration is not
      recognized, major complications may follow. In this study the authors used
      historical consecutive controls to compare the incidence of orbital penetration,
      identification of the natural ostium and lacrimal apparatus injury by the
      traditional surgical technique and a new technique of uncinectomy. Six hundred
      and thirty-six uncinectomies have been performed using the 'swing-door'
      technique. The 636 uncinectomies performed prior to changing techniques were used
      as historical controls. The incidence of orbital penetration (six compared to 0;
      p < 0.05) and ostium non-identification (42 not identified as compared to 0; p <
      0.001) was significantly less with the new technique. One lacrimal injury
      occurred with the 'swing-door' technique compared to zero with the standard
      technique (p > 0.05). The techniques are described and the complications
      discussed. The authors recommend this technique as it is easy to learn, allows
      removal of the uncinate flush with the lateral nasal wall and allows easy
      identification of the natural ostium of the maxillary sinus.

PMID- 9764295
TI  - Cyclin D1 expression as a prognostic factor in advanced hypopharyngeal carcinoma.
AB  - Hypopharyngeal carcinoma (HPC) has a poor prognosis. We investigated the
      expression of cyclin D1 in 34 advanced HPCs, and the value of cyclin D1
      expression was evaluated as a predictive marker in terms of the prognosis of HPC,
      compared with other clinical factors. Using immunohistochemical staining, 20 of
      34 patients showed positive immunoreactivity for cyclin D1. The statistical trend
      of the survival rate was lower in the cyclin D1-positive patients than in the
      cyclin D-negative ones (p = 0.0805). The predictive factors for the survival rate
      were effectiveness of neo-adjuvant chemotherapy (F = 8.698) (p = 0.0066), cyclin
      D1 expression (F = 6.244) (p = 0.0191) and N classification (F = 5.037) (p =
      0.0335). The cyclin D1-positive patients had approximately four-fold higher
      mortality than the cyclin D1-negative ones. These data indicate that the
      expression of cyclin D1, in advanced patients with hypopharyngeal carcinoma is a
      useful marker for prognosis.

PMID- 9764296
TI  - Microsurgical technique in thyroid surgery--a 10-year experience.
AB  - OBJECTIVE: To report the results of thyroid surgery in a University department of
      ENT--head and neck surgery, and to evaluate the benefits of the use of the
      surgical microscope in thyroid surgery. DESIGN: A retrospective evaluation of the
      records of all patients who underwent thyroid surgery in the 10-year period 1987
      1996. METHODS: In addition to standard surgical principles the Zeiss multi
      discipline universal surgical microscope with a 250 mm ocular lens was used in
      all cases. Total thyroidectomy was performed in all malignant cases, while
      unilateral lobectomy plus isthmus resection was the standard procedure in benign
      cases. PATIENTS: There were 573 patients, aged 11-87 years, 444 females and 129
      males. Four hundred and fifty-one had benign lesions, 122 malignant. Four hundred
      and eighty-nine had primary surgery, 84 underwent completion surgery or surgery
      for recurrent disease. RESULTS: Primary thyroid gland surgery in benign/malignant
      disease resulted in permanent recurrent laryngeal nerve palsy in 0.6 per cent/3.5
      per cent of the patients respectively, when calculated as nerves at risk (NAR).
      In benign recurrent or malignant completion surgery this complication rate was
      4.5 per cent/2.9 per cent respectively. CONCLUSION: Thyroid surgery in our
      University ENT--Head and Neck Department with the use of the surgical microscope
      provides pleasing results, especially considering the diversity of surgeons, due
      to the departments' teaching responsibilities.

PMID- 9764297
TI  - Use of a disposable electrode for recurrent laryngeal nerve monitoring.
AB  - Our experience with a non-invasive, disposable electrode for intra-operative
      identification and monitoring of the recurrent laryngeal nerve is described. The
      electrode system, while simply attached to the endotracheal tube, acts as a
      laryngeal surface electrode and detects electromyographic activity of the
      intrinsic laryngeal muscles when the recurrent laryngeal nerve is stimulated. We
      have successfully used this electrode to monitor 19 recurrent laryngeal nerves in
      15 patients who have undergone partial or total thyroidectomy. We feel that this
      device can be useful particularly in cases of re-exploration and malignancies of
      the thyroid gland.

PMID- 9764298
TI  - Aural papillomatosis--treatment with the carbon dioxide laser.
AB  - Aural papillomatosis has been infrequently reported in the English literature. It
      is a condition which can be very difficult to treat. We present the first
      reported case of aural papillomatosis successfully treated with the CO2 laser.

PMID- 9764299
TI  - Cochlear implantation in a patient with grand mal epilepsy.
AB  - A case is reported in which a Nucleus 22 channel intracochlear implant was used
      to treat a deaf Hungarian woman (aged 37 years) with a 34-year history of grand
      mal (GM) epilepsy maintained on carbamazepine-diazepam combination therapy who
      had not benefited from conventional hearing aids. Pre-operative electrical
      stimulation of the acoustic nerve, however, exhibited a good nerve function with
      no evidence of abnormal waveforms in the electroencephalogram (EEG). Successful
      intracochlear insertion of the 22 electrode resulted in a 40 dB hearing
      improvement at frequencies 250-2000 Hz in the implanted ear with no signs of
      pathologic wave activity at either the previously recognized epileptic focus
      (fronto-precentral region) or indeed, in other regions of the brain at use of the
      implant. We conclude that intracochlear implantation per se is not a hazardous
      intervention in patients with fronto-precentral epileptic foci.

PMID- 9764300
TI  - Frontal sinolith.
AB  - We report on a case of an endogenous frontal sinolith and a literature review of
      classification and use of the terms rhinolith, and sinolith.

PMID- 9764301
TI  - Rheumatoid nodules of the larynx.
AB  - A 67-year-old woman with rheumatoid arthritis was hospitalized because of
      dysphagia and severe nodulosis. Over a two-year period the patient had been
      treated with methotrexate. A computed tomography (CT) scan of the neck showed a 2
      x 2 cm large tumour behind the top left lateral thyroid cartilage. A biopsy taken
      during direct laryngoscopy showed it was a rheumatic nodule. Treatment with
      colchicine reduced the patient's dysphagia. As methotrexate is used increasingly
      in the treatment of rheumatoid arthritis and as this particular drug causes
      rheumatic nodules in five to 10 per cent of the patients, it must be foreseen
      that the incidence of nodules in the upper airways will increase.

PMID- 9764302
TI  - Invasive laryngeal candidiasis: a cause of stridor in the previously irradiated
      patient.
AB  - Upper airway obstruction is always a serious condition. In patients who have
      previously been irradiated for a laryngeal malignancy, it normally implies either
      residual or recurrent disease. We report a case of stridor due to invasive
      laryngeal candidiasis in a patient who had undergone radiotherapy for a T1a N0
      squamous cell carcinoma of the glottis eight months earlier. Extensive
      investigation failed to identify recurrence of disease and the patient responded
      to prolonged topical antifungal therapy. Infection with Candida species is most
      frequently found in debilitated or immunocompromised patients. Although cases of
      upper airway obstruction in children secondary to idiopathic laryngeal
      candidiasis have been reported, to our knowledge no such presentation has been
      described in adults. This report highlights the difficulty of diagnosis and
      treatment. Familiarity with candidal infection is important for early diagnosis
      and appropriate treatment.

PMID- 9764303
TI  - Primary tuberculous tracheitis.
AB  - We report a case of primary tuberculous tracheitis in an otherwise healthy woman
      who presented with cough and stridor due to diffuse tracheal narrowing by
      tuberculous pseudomembranous lesion, which resolved completely with
      antituberculosis chemotherapy.

PMID- 9764304
TI  - Tonsillar metastasis from malignant pulmonary carcinoid tumour.
AB  - Tumour metastases to the tonsil are rare and are usually due to spread from
      malignant melanoma and carcinomas of the breast, lung, kidney or stomach. We
      describe the clinical and histological findings of a tonsillar metastasis from a
      malignant pulmonary carcinoid tumour, an occurrence not previously reported.

PMID- 9764305
TI  - Recurrent unilateral tonsillitis secondary to a penetrating foreign body in the
      tonsil.
AB  - We report a case of an impacted foreign body in the tonsil presenting as
      recurrent unilateral tonsillitis. A completely embedded foreign body should be
      considered in cases of recurrent unilateral tonsillitis.

PMID- 9764306
TI  - Tuberculosis of the mandible in a child.
AB  - The incidence of notification of tuberculosis is increasing in the developed
      world. The disease has a variable mode of presentation and therefore diagnosis is
      not easy. We present an unusual case of tuberculosis involving the ramus of the
      mandible in a six-year-old boy and outline its management.

PMID- 9764307
TI  - Tuberculosis of the parotid gland.
AB  - The presentation of tuberculosis as an isolated parotid lump is rare. In this
      paper, six cases with tuberculous parotitis are reported which were evaluated as
      a benign parotid neoplasm in 216 specimens pre-operatively. All but one of them
      had no previous history of tuberculosis and all had a parotid lump as a sole
      symptom for at least one year. The diagnosis of tuberculosis was made, after
      superficial parotidectomy, by histopathology. Parenchymal involvement and
      intraparotid lymph node involvement with tuberculosis were seen in five and three
      patients, respectively. Two of the patients had lymph node involvement outside
      the parotid area. One of six patients had a coincidental Warthin tumour. A
      surgical approach is not only therapeutic but also diagnostic when other
      diagnostic tools fail.

PMID- 9764308
TI  - Lymphoblastic lymphoma/leukaemia presenting as perichondritis of the pinna.
AB  - Extra-nodal non-Hodgkin's lymphoma (NHL) of the pinna has only been reported once
      in a patient with immunodeficiency. We report an unusual case of lymphoblastic
      lymphoma in a patient without any immunodeficiency, presenting as an inflammatory
      lesion of the pinna, which illustrates the need to biopsy any non-healing lesion
      as soon as possible to ensure that such a treatable malignancy is diagnosed at an
      early stage.

PMID- 9764309
TI  - The use of magnetic resonance imaging to assess tracheal stenosis following
      percutaneous dilatational tracheostomy.

PMID- 9764310
TI  - Transport and transformations of yolk lipids during development of the avian
      embryo.

PMID- 9764311
TI  - Phytooxylipins and plant defense reactions.

PMID- 9764312
TI  - Health care in refugee camps.

PMID- 9764313
TI  - Royal Society of Tropical Medicine and Hygiene meeting at Manson House, London,
      20 March 1997. Epidemiology and control of rabies. The growing problem of rabies
      in Africa.
AB  - Although rabies in Africa is relatively insignificant in terms of human
      mortality, the disease is still relevant because of the high costs of rabies
      prevention. Over the past 2 decades, demographic, economic and sociopolitical
      trends in Africa have increasingly favoured the persistence and spread of rabies,
      while limiting the effectiveness of control measures. Dog rabies predominates
      throughout most of Africa; the domestic dog is the principal reservoir host as
      well as the most important source of infection for people. However, wild-life
      rabies is increasingly a concern, both as a threat to endangered wildlife
      populations and because of the possible emergence of new maintenance hosts.

PMID- 9764314
TI  - Comparison of the effect of insecticide-treated bed nets and DDT residual
      spraying on the prevalence of malaria transmitted by Anopheles anthropophagus in
      China.
AB  - In order to improve the control of malaria in a problem part of Hubei Province,
      China, where Anopheles anthropophagus is the vector of Plasmodium vivax,
      insecticide treatment of bed nets was introduced. The people were given the
      choice of DDT residual spraying, which had been used for many years, or
      deltamethrin treatment of their bed nets. Two counties, in which these 2
      different methods had been introduced, and an untreated area were evaluated. DDT
      house spraying and insecticide treated bed nets were equally effective, but
      deltamethrin treatment was cheaper and so was considered the method of choice.

PMID- 9764315
TI  - A cost-benefit analysis of Chagas disease control in north-western Argentina.
AB  - Chagas disease has been controlled in the Department of Anta, Province of Salta,
      Argentina, through a series of vector control interventions beginning in 1983.
      Based on data from this programme, together with estimates of the value of
      benefits accruing to the programme due to avoidance of new cases of Chagas
      disease, we present an analysis of costs and benefits of the vector control
      interventions. Under all assumptions, the interventions have been highly
      profitable from a societal point of view, with an internal rate of return in
      excess of 60%. The net present value of benefits accruing to the programme is
      estimated to be above US$7 million.

PMID- 9764316
TI  - The proportion of helminth infections in a community in western Kenya which would
      be treated by mass chemotherapy of schoolchildren.
AB  - The present study used data from a community-based epidemiological survey of 752
      persons in 3 villages in Kisumu District, western Kenya, to examine the
      proportion of infected persons who would be treated, as well as the effect on
      helminth egg production, if anthelmintics were provided to schoolchildren.
      Overall prevalences of hookworm, Ascaris lumbricoides, Trichuris trichiura and
      Schistosoma mansoni infections were 63%, 16%, 24% and 24% respectively, and
      intensities were low for all infections. Only 79% of the school-aged children
      were enrolled. For all 4 infections, a school-based programme would treat between
      76% and 86% of infected school-age children and would theoretically eliminate
      between 83% and 92% of the number of eggs excreted by this age group. Of the
      total population, school-based programmes would treat only between 31% and 50% of
      the infected persons and eliminate only 15%, 46%, 29% and 27% of the total number
      of hookworm, Ascaris, Trichuris and S. mansoni eggs excreted, respectively.
      Provided that school attendance rates were high in the study area, school-based
      programmes would be efficient in improving the helminth infection status of
      school-aged children. On the other hand, adults, non-enrolled school-aged
      children and preschool children not offered treatment represented more than half
      of the helminth-infected persons and they excreted between half and 85% of the
      total burden of helminth eggs in the area. Hence, mass chemotherapy of
      schoolchildren would be less effective in the control of at least hookworm and S.
      mansoni infections in this specific community. There should therefore be a
      community-based approach to helminth control in combination with a school-based
      programme.

PMID- 9764317
TI  - Correlation between positive serology for Plasmodium vivax-like/Plasmodium
      simiovale malaria parasites in the human and anopheline populations in the State
      of Acre, Brazil.
AB  - Antibodies against the Plasmodium vivax-like/P. simiovale malaria parasite
      circumsporozoite repeat peptide (APGANQEGGAA)3 were determined by enzyme-linked
      immunosorbent assay (ELISA) in 120 sera randomly collected in 1994 from adults in
      3 localities of the malaria endemic area in the State of Acre, Brazil; antibody
      was detected in 18 (15%). A 'sandwich' ELISA using monoclonal antibody (mab) Pam
      172, directed against the same peptide, was carried out on 1207 Anopheles
      oswaldoi, 12 of which (1.0%) were positive, and 168 A. deaneorum, 2 of which
      (1.2%) were positive. This is the first report of serological detection of the P.
      vivax-like parasite in anophelines and the first report linking anopheline to
      human serology for this parasite in the same geographical area. It is an
      additional indication that A. oswaldoi is a malaria vector in Acre.

PMID- 9764318
TI  - The role of four anopheline species (Diptera: Culicidae) in malaria transmission
      in coastal Tanzania.
AB  - Malaria is holoendemic in coastal Tanzania with Anopheles funestus and members of
      the A. gambiae complex being mainly responsible for transmission. Over a 4
      months' sampling period 2222 anopheline mosquitoes were collected using light
      traps and indoor resting catches, of which 58.6% were A. gambiae, 7.6% A.
      arabiensis, 6.9% A. merus and 26.9% A. funestus. Plasmodium falciparum
      circumsporozoite antigen (CSA) rates were: A. funestus 6.05% (n = 479), A.
      gambiae 8.4% (n = 1042), A. arabiensis 7.3% (n = 136) and A. merus 9.8% (n =
      122). The P. malariae CSA rate for all anophelines was 0.07% (n = 1862).
      Estimated sporozoite densities were less than 2000 for at least 50% of all the
      positive mosquitoes. Along the coast the abundance of A. merus (41.3%) and A.
      gambiae (46.1%) was similar, and their CSA rates were comparable (11.6% and
      12.5%, respectively) and higher than those for A. arabiensis (7.7%) and A.
      funestus (4.6%). These results indicate that A. merus plays an unexpectedly
      important role in malaria transmission in coastal Tanzania.

PMID- 9764319
TI  - Phylogenetic species and domesticity of Lutzomyia whitmani at the southeast
      boundary of Amazonian Brazil.

PMID- 9764320
TI  - Prevalence of tuberculosis in TB suspects with short duration of cough.
AB  - The prevalence of pulmonary tuberculosis (PTB) in patients with short duration of
      cough was determined. Ninety-eight adult out-patients (60 men, 38 women; mean age
      32 years) at Queen Elizabeth Central Hospital, Blantyre, Malawi, who had cough
      for 1-3 weeks which was unresponsive to a course of antibiotics, were
      successfully screened by microscopy and culture of 2 or 3 sputum specimens and
      chest radiography; 34 (35%) had PTB. Ten patients were sputum smear-positive and
      24 were smear-negative and culture-positive. There was no difference in age,
      gender or clinical features of general illness, respiratory disease and HIV
      related disease between patients with PTB and those with no evidence of PTB. Nine
      patients (26%) with microbiologically confirmed tuberculosis (TB) had chest
      radiograph abnormalities consistent with TB, compared with 5 (8%) of patients
      with no microbiological evidence of TB. Certain classes of patients with a short
      history of cough would benefit from PTB screening strategies with the emphasis on
      sputum examination rather than chest radiography, which is unreliable in such
      patients. The classes include (i) patients with other features of TB whose cough
      has not improved with antibiotic therapy, (ii) seriously ill patients, and (iii)
      patients in high risk institutions such as prisons and refugee camps.

PMID- 9764321
TI  - Aetiology of cholera in Tamil Nadu: recent observations.
AB  - Vibrio cholerae was isolated from 1008 of 3496 stool samples (28.8%) examined in
      Tamil Nadu State, India, between November 1992 and December 1995. During November
      and December 1992, 363 of the 370 isolates serotyped (98%) were V. cholerae O139
      (Bengal). The epidemic predominantly affected adults (91%; 597/656). Both V.
      cholerae O1 and O139 serotypes were sometimes isolated in the same locality from
      different individuals. From January 1993 onwards, the rate of isolation of V.
      cholerae O139 declined, and in 1995 V. cholerae E1 Tor (serotype O1) was isolated
      from most of the cases (85.6%; 131/153). V. cholerae E1 Tor has clearly not been
      replaced by serotype O139, but can survive during inter-epidemic periods and
      reappear at an opportune moment. The decline of serotype O139 may be due to the
      development of immunity as a result of repeated exposure.

PMID- 9764322
TI  - Comparison of the ParaSight-F test and the ICT Malaria Pf test with the
      polymerase chain reaction for the diagnosis of Plasmodium falciparum malaria in
      travellers.
AB  - Rapid and accurate methods are needed for the diagnosis of imported malaria. The
      ParaSight-F test and the ICT Malaria Pf test are commercially available kits
      marketed for the diagnosis of Plasmodium falciparum malaria. Both tests are
      antigen-capture assays based on the detection of P. falciparum histidine-rich
      protein 2 in peripheral blood. Using microscopy and a polymerase chain reaction
      (PCR)-based method as reference standards, we performed a 'blinded' comparison of
      these assays for the detection of P. falciparum infection in 200 febrile
      travellers returning from malaria-endemic areas. As determined by PCR and
      microscopy, 148 travellers had malaria and, of these patients, 54.7% (81/148)
      were infected with P. vivax only, 31.1% (46/148) with P. falciparum only, 9.5%
      (14/148) with P. ovale, 0.7% (1/148) with P. malariae, and 4.1% (6/148) had mixed
      infections. Compared to PCR, the ParaSight-F and ICT Malaria Pf tests had initial
      sensitivities of 94% and 90% and specificities of 95% and 97%, respectively, for
      the detection of P. falciparum malaria. When discrepant samples were retested
      with day 0 and day 1 bloods, the sensitivities improved to 96% and 94%,
      respectively. The 2 remaining false negative results with the Para-Sight-F test
      and 2 of the 3 false negative results with the ICT Malaria Pf test occurred in
      samples with < 100 parasites/microL. The performance of these kits was not
      significantly different (P = 0.75) and both are simple, rapid, and accurate tests
      for the detection of P. falciparum infection in the returned traveller.

PMID- 9764323
TI  - Reactive nitrogen intermediates and outcome in severe adult malaria.
AB  - The role of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) in the
      pathophysiology of severe falciparum malaria remains unclear. We conducted a
      retrospective case-control study of Vietnamese adults with severe malaria to
      determine the relationship between outcome and admission plasma reactive nitrogen
      intermediates (RNI), the stable metabolites of NO. The study was designed to take
      into account the potential confounders of recent dietary nitrogen intake and
      renal function. Seventy-six patients who died from severe malaria were matched
      for age and sex with 76 survivors from a prospectively studied series of 560
      patients. Median untransformed unadjusted plasma RNI levels were slightly higher
      in fatal cases (45 mumol/L, range 0-482) than in survivors (24.1 mumol/L, range
      1.4-466) (P = 0.031, Wilcoxon signed-rank). There was a significant positive
      correlation between RNI levels and plasma creatinine (Spearman's rho = 0.35, P <
      0.0001), and the addition of plasma creatinine as a covariate in a multivariate
      analysis abolished the trend towards higher RNI levels in fatal cases (P for the
      coefficient for RNI = 0.96). There was no association between RNI levels and
      either depth of coma on admission or time to regain consciousness. These findings
      do not support a pivotal role for systemic generation of NO in the pathogenesis
      of severe malaria in general, or cerebral malaria in particular.

PMID- 9764324
TI  - Estimating Plasmodium vivax parasitaemia.

PMID- 9764325
TI  - Post kala-azar ocular leishmaniasis.
AB  - The clinical features, diagnosis and treatment of 6 patients with post kala-azar
      ocular leishmaniasis are described. The eye lesions were associated with past or
      concomitant post kala-azar dermal leishmaniasis (PKDL). Four patients had post
      kala-azar leishmanial conjunctivitis and blepharitis. Using the polymerase chain
      reaction, the causative parasite was characterized as Leishmania donovani in 2 of
      these 4 patients. Two patients had post kala-azar anterior uveitis. The diagnosis
      of uveitis was based on the clinical manifestations, temporal relation to treated
      visceral leishmaniasis, the association with PKDL and positive anti-Leishmania
      serology. All patients were treated with systemic sodium stibogluconate. Patients
      with anterior uveitis were also treated with steroid and atropine eyedrops. The
      response to treatment was good. The importance of early diagnosis and treatment
      of ocular leishmaniasis is stressed.

PMID- 9764326
TI  - Human diphyllobothriasis: first report from India.

PMID- 9764327
TI  - Salmonella meningitis in Thai infants: clinical case reports.
AB  - Between June 1988 and September 1996 12 of 65 infants (18%) admitted to the
      Department of Pediatrics, Ramathibodi Hospital, Bangkok, Thailand with purulent
      meningitis were infected with Salmonella spp. Their ages ranged from 1.5 to 6
      months. Six of the infants had diarrhoea, 9 had seizures, and 11 had subdural
      effusion or empyema. Six infants required surgical treatment; 2 had brain
      abscesses. Salmonella was recovered from the cerebrospinal fluid of 11 infants
      and from the subdural fluid of 10. Eight infants were successfully treated with
      cefotaxime alone or in combination with co-trimoxazole, one with co-trimoxazole,
      and one with the combination of co-trimoxazole and ampicillin. The duration of
      treatment was 6 weeks, except for one patient who had a large brain abscess and
      was treated for 8 weeks. The last 2 patients, despite the fact that the organisms
      were susceptible to cefotaxime, failed to respond clinically to appropriate doses
      of it. Both were cured after ciprofloxacin was added to the therapy.
      Ciprofloxacin is probably the drug of choice to be used in addition to the
      previously used antibiotics for severe cases of Salmonella meningitis in infants.

PMID- 9764328
TI  - Dual infection with Vibrio cholerae serogroups O1 and O139.

PMID- 9764329
TI  - First report of human leptospirosis due to Leptospira interrogans serovar
      javanica in India.

PMID- 9764330
TI  - Hypercalcaemia and paracoccidioidomycosis.

PMID- 9764331
TI  - The evolution of multiple drug resistance in malaria parasites.
AB  - Forces determining the rate of spread of drug resistance in malaria were explored
      using a genetics transmission model which took account of the strong population
      structure of these parasites. The rate of change of frequency of drug resistant
      mutants in the parasite population is primarily a function of the proportion of
      hosts treated with drugs, and parasite transmission rates. With high transmission
      rates, selection by drugs is more effective than with lower rates because the
      resistant mutant passes on more copies of itself to the next generation of hosts.
      Thus reducing transmission rates, either at the overall population level or from
      drug-treated individuals, should be effective in curbing the spread of
      resistance. An exception to this is when 2 unlinked genes act jointly (not
      independently) to confer resistance, when the prevailing transmission rate is
      already low, drug use is minimal, and resistance genes are rare. Reductions in
      fitness of the mutant in the absence of drugs (i.e., a fitness cost to
      resistance) and the degree of epistasis and the mode of gene action of the drugs
      do not alter these conclusions.

PMID- 9764332
TI  - Quinine sensitivity of isolates of Plasmodium falciparum from the coast of Kenya.

PMID- 9764333
TI  - Resistance in vivo of Plasmodium falciparum to co-trimoxazole in western Uganda.
AB  - In the context of the 'integrated management of childhood illnesses' (IMCI)
      programme the World Health Organization recommends treating children in malarious
      areas presenting with fever and respiratory symptoms with co-trimoxazole. In
      order to verify its effectiveness in uncomplicated Plasmodium falciparum malaria
      we carried out a study in vivo in western Uganda: 180 children under 5 years old
      were enrolled and treated with 40/8 mg/kg/d co-trimoxazole over 5 d, and 159
      could be followed on days 3, 7 and 14. Effectiveness of treatment was found to be
      significantly different in various parts of the study area. In Bundibugyo
      District, bordering Republique Democratique du Congo (Zaire), 59.1% (39/66) of
      children were clinically cured after 14 d and 56.1% were parasitologically cured.
      In the east of Kabarole District (43 children), the figures were 76.7% and 65.1%,
      respectively. In western Kabarole (50 children) the rates were 96.0% and 90.0%,
      respectively. We conclude that, in view of the high level of clinical failures in
      parts of the study area, co-trimoxazole should not be used in the IMCI programme
      for combined treatment of malaria and pneumonia in the region. Assessment of
      therapeutic effectiveness of antimalarial drugs needs to consider the
      microepidemiology of resistance.

PMID- 9764334
TI  - Efficacy and pharmacokinetics of atovaquone and proguanil in children with
      multidrug-resistant Plasmodium falciparum malaria.
AB  - A trial was conducted in 32 Thai children with uncomplicated multidrug-resistant
      falciparum malaria to assess the efficacy, safety and pharmacokinetics of
      atovaquone and proguanil; plasma concentrations of atovaquone, proguanil and its
      metabolite, cycloguanil, were measured in a subset of 9 children. The children
      received atovaquone (17 mg/kg/d for 3 d) plus proguanil (7 mg/kg/d for 3 d).
      Twenty-six children who had only Plasmodium falciparum infection and remained in
      hospital for 28 d were assessed for drug efficacy. The combination regimen
      produced a cure rate of 100%. Parasite and fever clearance times were 47 h (range
      8-75) and 50 h (range 7-111), respectively. Atovaquone and proguanil were rapidly
      absorbed, with median time to peak concentrations of 6 h (range 6-24) and 6 h
      (range 6-12), respectively. Peak concentrations of cycloguanil were achieved
      between 6 and 12 h (median 6) after administration of proguanil. Mean peak plasma
      concentration of atovaquone on day 3 was 5.1 micrograms/mL (SD = 2.1). The day 3
      mean peak plasma concentration of proguanil was 306 ng/mL (SD = 108) compared
      with 44.3 ng/mL (SD = 27.3) for cycloguanil. Mean values for the AUC (area under
      plasma concentration-time curve) were 161.8 micrograms/mL.h (SD = 126.9) for
      atovaquone, 4646 ng/mL.h (SD = 1226) for proguanil, and 787 ng/mL.h (SD = 397)
      for cycloguanil. Terminal elimination half-lives of atovaquone, proguanil and
      cycloguanil were estimated as 31.8 h (SD = 8.9), 14.9 h (SD = 3.3) and 14.6 h (SD
      = 2.6), respectively. No major adverse effect was attributable to the study
      drugs. Atovaquone/proguanil combination is safe and highly effective, and should
      be especially valuable for treatment of multidrug-resistant falciparum malaria.

PMID- 9764335
TI  - Artesunate and mefloquine in the treatment of uncomplicated multidrug-resistant
      hyperparasitaemic falciparum malaria.
AB  - Oral artesunate is the most effective treatment for uncomplicated
      hyperparasitaemia in falciparum malaria. To assess the contribution of mefloquine
      to therapeutic efficacy in an area endemic for mefloquine-resistant Plasmodium
      falciparum, an open randomized comparison of a 5 d course of oral artesunate
      (total dose 12 mg/kg) with and without a single dose of mefloquine (25 base
      mg/kg) was conducted in 100 adults and children with uncomplicated
      hyperparasitaemia (> 4% parasitized red blood cells). Both regimens were well
      tolerated and gave equally rapid clinical responses (84% of patients were
      aparasitaemic and 96% were afebrile within 48 h), but the recrudescence rate
      assessed at day 42 was 6% in those receiving artesunate with mefloquine compared
      to 36% in those receiving artesunate alone (adjusted hazard ratio 7, 95%
      confidence interval [95% CI] 2-32; P < 0.01). In addition, the efficacy of a 7 d
      course of artesunate, with and without the addition of mefloquine, was monitored
      in 178 patients who were not part of the randomized comparison. The failure rate
      was again lower in those receiving artesunate and mefloquine--7% (95% CI 2-13)
      compared with 26% (95% CI 8-44) in patients treated with artesunate alone. An
      oral regimen of 5 d or more of artesunate, together with mefloquine (25 mg/kg)
      given on day 2, is an effective treatment for uncomplicated hyperparasitaemic
      falciparum malaria in this area of high level multidrug resistance.

PMID- 9764336
TI  - Amodiaquine as the first-line treatment of malaria in Yaounde, Cameroon:
      presumptive evidence from activity in vitro and cross-resistance patterns.

PMID- 9764338
TI  - Direct assessment in vivo of the efficacy of combined single-dose ivermectin and
      diethylcarbamazine against adult Wuchereria bancrofti.
AB  - When ivermectin and diethylcarbamazine (DEC) are given simultaneously in a single
      dose to persons with Wuchereria bancrofti infection, the resulting suppression of
      microfilaraemia is more profound and sustained than when either drug is given
      alone. To assess whether this effect is a result of enhanced macrofilaricidal
      efficacy, we used ultrasound to monitor the adult worms in the scrotal area of
      men with W. bancrofti microfilaraemia. Twenty-one men were treated simultaneously
      with DEC (6 mg/kg) and either 200 micrograms/kg or 400 micrograms/kg of
      ivermectin (11 and 10 men, respectively). Ten other men received a single 200
      micrograms/kg dose of ivermectin followed 5 d later by a 6 mg/kg dose of DEC
      (sequential treatment). All men became amicrofilaraemic after treatment and all
      except one remained so for one year. Cessation of adult worm movement, indicative
      of death of all the adult worms in a given 'nest', was observed in none of 30
      nests in men who received simultaneous treatment and in 3 of the 19 nests (16%)
      in the men who received sequential treatment (P = 0.05). Scrotal nodules were
      detected in 5 of 21 men (24%) who received simultaneous treatment and in 8 men
      (80%) who received sequential treatment (P < 0.01). Thus, co-administration of
      ivermectin with DEC seems to interfere with the macrofilaricidal action of DEC.
      These findings have implications both for treatment of the individual patient and
      for community-based drug distribution programmes designed to interrupt
      transmission of W. bancrofti.

PMID- 9764337
TI  - Effect of iron chelation therapy on mortality in Zambian children with cerebral
      malaria.
AB  - To examine the effect of iron chelation on mortality in cerebral malaria, we
      enrolled 352 children in a trial of deferoxamine in addition to standard quinine
      therapy at 2 centres in Zambia, one rural and one urban. Entrance criteria
      included age < 6 years, Plasmodium falciparum parasitaemia, normal cerebral
      spinal fluid, and unrousable coma. Deferoxamine (100 mg/kg/d infused for a total
      of 72 h) or placebo was added to a 7 d regimen of quinine that included a loading
      dose. Mortality overall was 18.3% (32/175) in the deferoxamine group and 10.7%
      (19/177) in the placebo group (adjusted odds ratio 1.8; 95% confidence interval
      0.9-3.6; P = 0.074). At the rural study site, mortality was 15.4% (18/117) with
      deferoxamine compared to 12.7% (15/118) with placebo (P = 0.78, adjusted for
      covariates). At the urban site, mortality was 24.1% (14/58) with deferoxamine and
      6.8% (4/59) with placebo (P = 0.061, adjusted for covariates). Among survivors,
      there was a non-significant trend to faster recovery from coma in the
      deferoxamine group (adjusted odds ratio 1.2; 95% confidence interval 0.97-1.6; P
      = 0.089). Hepatomegaly was significantly associated with higher mortality, while
      splenomegaly was associated with lower mortality. This study did not provide
      evidence for a beneficial effect on mortality in children with cerebral malaria
      when deferoxamine was added to quinine, given in a regimen that included a
      loading dose.

PMID- 9764339
TI  - Treatment of human lagochilascariasis with ivermectin: first case report from
      Ecuador.

PMID- 9764340
TI  - Plasmodium falciparum: genetic polymorphism of the merozoite surface antigen 2
      gene of strains from India.

PMID- 9764341
TI  - Measles antibody levels in a vaccinated population in Brazil.
AB  - An epidemiological study of measles-specific immunoglobulin G antibody levels was
      conducted using a representative sample of a vaccinated suburban population in
      Sao Paulo State, Brazil. The study aimed to determine immunity status in relation
      to age and infection or vaccination experience. 549 age-structured samples of
      sera, collected in 1990, were screened and calibrated to the international
      reference serum, using measles nucleoprotein in an enzyme immunoassay. In the age
      group with direct experience of vaccination (9 months to 15 years), whether
      routine or campaign, over 90% had detectable antibody > or = 50 miu/mL. However,
      14% of these had antibody concentrations between 50 and 100 miu/mL and 30%
      between 50 and 255 miu/mL. In those over 15 years of age, 94% had antibody levels
      > 255 miu/mL, assumed to be the result of past infection. The study suggested
      that, within highly vaccinated populations, a proportion of individuals had
      measles antibody levels which may be insufficient to protect against reinfection
      or clinical disease. The implications of these results, and similar findings
      elsewhere, in relation to the persistence of measles requires investigation; this
      has particular relevance in Sao Paulo following the recent measles outbreak.

PMID- 9764342
TI  - The Anopheles gambiae complex: a new species from Ethiopia.
AB  - Historically, members of the Anopheles gambiae complex from Ethiopia have been
      identified chromosomally as either A. arabiensis or A. quadriannulatus. Recent
      collections from the Jimma area in Ethiopia, southwest of Addis Ababa, revealed
      29 specimens of A. quadriannulatus based on the standard polymerase chain
      reaction (PCR) identification method. 'Wild' females were induced to lay eggs and
      the progeny reared as individual families. Resulting adults were cross-mated to a
      laboratory colony strain of A. quadriannulatus originating from the Kruger
      National Park, South Africa. Hybrid progeny were obtained only from the colony
      female x Ethiopian male cross. This cross produced a female/male sex ratio of
      0.48. Male offspring were sterile and ovarian polytene chromosomes from hybrid
      females showed typical asynapsis as expected in interspecific crosses within the
      A. gambiae complex. The X chromosomes, although apparently having homosequential
      banding patterns, were usually totally asynapsed. All autosomes were
      homosequential. The lack of inversion heterozygotes, in both the wild and hybrid
      samples, may simply be a reflection of the small sample size. Until such time as
      the Ethiopian species can be formally described and assigned a scientific name,
      it is provisionally designated Anopheles quadriannulatus species B because of its
      close similarity to this species.

PMID- 9764343
TI  - Asymptomatic Plasmodium falciparum parasitaemia in pregnant women.

PMID- 9764345
TI  - The Varna meeting resumes after 10 years.

PMID- 9764344
TI  - Onchocerciasis, epilepsy and hyposexual dwarfism.

PMID- 9764347
TI  - Levels of antibodies to transferrin and alpha 2-HS glycoprotein in women with and
      without endometriosis.
AB  - PROBLEM: To establish an enzyme-linked immunosorbent assay (ELISA) for
      determining the levels of antibodies to transferrin and alpha 2-HS glycoprotein
      in the serum of women with and without endometriosis. METHOD OF STUDY: Serum
      samples were obtained from 105 normal women, who were randomly selected for a
      population-based epidemiologic study, and 123 patients with active endometriosis.
      An ELISA using transferrin and alpha 2-HS glycoprotein as antigens was
      established. RESULTS: The levels of antibodies to transferrin and alpha 2-HS
      glycoprotein in the serum of patients with endometriosis were approximately 21
      times higher than those in the serum of control subjects without endometriosis.
      Only 2% of control subjects had false positive levels of these antibodies, and 5%
      of patients with endometriosis had false negative levels of these antibodies
      (specificity, 98.1 and 98.1, respectively, for anti-transferrin and anti-alpha 2
      HS glycoprotein; sensitivity, 95 and 96.7, respectively, for anti-transferrin and
      anti-alpha 2-HS glycoprotein). CONCLUSIONS: Patients with endometriosis have
      significantly higher levels of antibodies to transferrin and alpha 2-HS
      glycoprotein than control subjects. Testing women for antibodies to transferrin
      and alpha 2-HS glycoprotein will provide a specific noninvasive diagnosis of
      endometriosis.

PMID- 9764348
TI  - The selective use of heparin/aspirin therapy, alone or in combination with
      intravenous immunoglobulin G, in the management of antiphospholipid antibody
      positive women undergoing in vitro fertilization.
AB  - PROBLEM: The effect of mini-dose heparin/aspirin (H/A) alone vs. combined
      intravenous immunoglobulin G (IVIg) and H/A on in vitro fertilization (IVF)
      birthrates in women who test seropositive for antiphospholipid antibodies (APA+)
      was evaluated, as was the question of whether outcome is influenced by the
      gammaglobulin isotype(s) or the phospholipid (PL) epitope(s) to which the APAs
      are directed. METHOD OF STUDY: A case-control study was conducted in three
      phases, spanning a 4-year period, in a multicenter clinical research environment.
      Six hundred eighty-seven APA+ women, who were younger than 40 years and who each,
      completed up to three consecutive IVF/embryo transfer cycles within a 12-month
      period, were given either H/A alone or H/A in combination with IVIg. Birthrates
      relative to the type of immunotherapy (i.e., H/A alone and H/A with IVIg) and APA
      profile were the main outcome measurements. RESULTS: In phase I, 687 women who
      tested APA+ to one or more PL epitopes underwent two or fewer IVF attempts for a
      total of 1050 IVF cycles. Four hundred seventy-seven (46%) births occurred in 923
      IVF cycles in which H/A alone was administered. Twenty-two (17%) births occurred
      after 127 IVF cycles in which H/A was not administered. In phase II, 322 of 687
      women tested positive for a single APA subtype. These subjects underwent up to
      two consecutive IVF attempts for a total of 521 IVF cycles while receiving H/A
      alone. The birthrate was significantly lower for women whose APAs were directed
      toward phosphatidylethanolamine (PE) or phosphatidylserine (PS) involving IgG or
      IgM isotypes than for women who had any other APA (17% vs. 43%). In phase III,
      121 women who did not achieve live births after two consecutive IVF attempts in
      which H/A alone was administered received IVIg in combination with H/A during
      their third consecutive IVF cycle. The birth rate was 41% after these IVF cycles
      when anti-PS or anti-PE involving IgG or IgM isotypes were present, as compared
      with 17% when H/A alone was administered. The IVF outcome did not improve when
      IVIg was administered in association with any other single APA. CONCLUSIONS: The
      treatment of APA+ women with H/A alone improves IVF birthrates. This benefit is
      selective in that it does not apply in cases in which IgG- or IgM-related APAs
      are directed against PE or PS. In such cases, the addition of IVIg significantly
      improves the outcome.

PMID- 9764349
TI  - Effect of human chorionic gonadotropin on cytokine production from human
      endometrial cells in vitro.
AB  - PROBLEM: To examine whether human chorionic gonadotropin (hCG) is involved in the
      regulation of interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and leukemia
      inhibitory factor (LIF) secretion from cultured human endometrial cells. METHOD
      OF STUDY: A mixed population of endometrial cells from six in vitro
      fertilization/embryo transfer patients was cultured and incubated with various
      doses of hCG (0, 1, 10, 50, 100, and 500 IU/ml) for 24 hr. IL-6, TNF-alpha, and
      LIF levels in the culture medium were measured with enzyme-linked immunosorbent
      assay. RESULTS: IL-6 and TNF-alpha levels were stimulated by hCG in a dose
      dependent manner. Stimulation of IL-6 and TNF-alpha levels by 500 IU/ml of hCG
      increased their production by 3.7- and 2.8-fold, respectively (P < 0.05).
      Stimulation of IL-6 by 100 IU/ml of hCG was also significant (P < 0.05). However,
      there was no significant effect of hCG on LIF secretion by endometrial cells (P =
      0.31). CONCLUSIONS: hCG is involved in the regulation of endometrial cytokine
      production from human endometrial cells in vitro. This finding supports the
      recently emerging notion that hCG could have important local roles within the
      uterus besides its well-known luteotrophic role on the corpus luteum for
      maintenance of pregnancy.

PMID- 9764350
TI  - Fas-fas ligand system-induced apoptosis in human placenta and gestational
      trophoblastic disease.
AB  - PROBLEM: The low frequency of maternal immune responses to paternally inherited
      fetal antigens raises the following question: What regulates the immunobiology of
      pregnancy? Data suggest that this state is the result of peripheral immune
      tolerance, an active process of immune-regulation in which activated T cells
      undergo apoptosis. We studied Fas ligand (FasL) expression and apoptosis in
      normal and pathologic placentas to find out whether the Fas-FasL-induced
      apoptosis takes place during implantation. METHOD OF STUDY: FasL expression in
      paraffin sections was detected using specific antibodies and confirmed with
      reverse transcriptase-polymerase chain reaction of total RNA from frozen
      placentas. Apoptosis was detected using the terminal deoxy (d)-UTP nick end
      labeling assay. RESULTS: FasL was found in the normal placenta and in gestational
      trophoblastic disease. Apoptotic leukocytes were localized to the maternal-fetal
      interface corresponding in localization with the distribution of FasL.
      CONCLUSIONS: We propose that FasL expression in the placenta is a mechanism
      responsible for the development of maternal immune tolerance specific for
      paternal alloantigens and operates in pathologic states characterized by
      trophoblastic invasion/proliferation.

PMID- 9764351
TI  - Placental isoferritin levels in pregnant patients with systemic lupus
      erythematosus and/or antiphospholipid syndrome.
AB  - PROBLEM: Low serum placental isoferritin (PLF), an immunosuppressive cytokine
      like protein, was found in women with underlying placento-vascular dysfunction,
      such as intrauterine growth retardation and preeclamptic toxemia. The possible
      contribution of this placental product in the assessment of pregnant patients
      with either systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome
      (APS) was investigated. METHOD OF STUDY: Seventy-five healthy pregnant women used
      as controls and 25 preselected pregnant patients with either SLE and/or APS were
      enrolled in the study. Study patients were in remission during conception and all
      patients agreed to give 5 ml of venous blood at midgestation. The samples were
      frozen and analyzed retrospectively. After delivery, pregnancy outcomes were
      gathered from hospital records. RESULTS: Seventeen (68%) women had uneventful
      pregnancies and deliveries (normal) whereas 8 (32%) showed pathologic obstetric
      outcomes. Mean midgestational serum PLF levels were similar in the control and
      normal outcome groups (87 U/ml), whereas significantly lower levels (37 U/ml)
      were measured in the pathologic outcome group. Using a cutoff level of 10 U/ml,
      85% from the normal outcome group and 15% from the pathologic outcome group were
      above this threshold level, with 60% specificity and 100% sensitivity.
      CONCLUSIONS: These preliminary data suggest that PLF values may reflect placento
      vascular functions. These may represent a predictive biomarker for developing
      obstetric complications in pregnant women with either SLE and/or APS.

PMID- 9764352
TI  - Circulating levels of immunoreactive cytokines in women with preeclampsia.
AB  - PROBLEM: Circulating inflammatory cytokines have been implicated in the
      pathogenesis of preeclampsia. To test this hypothesis, we measured plasma levels
      of immunoreactive tumor necrosis factor (TNF)-alpha and -beta, interleukin (IL)-1
      alpha and -beta, and IL-6 and -10 in women with preeclampsia, in women with
      transient gestational hypertension, and throughout normal pregnancy. METHOD OF
      STUDY: Enzyme-linked immunosorbent assays were used and subjected to extensive
      validation studies. RESULTS: The median concentration of plasma TNF-alpha was
      increased by twofold in women with preeclampsia compared with that in normal
      third-trimester pregnancy (P < 0.001) and in women with gestational hypertension
      (P < 0.04). The median concentration of plasma IL-6 was increased by threefold in
      women with preeclampsia compared with that in normal third-trimester pregnancy (P
      < 0.001) and increased twofold compared with that in women with gestational
      hypertension (P < 0.1). There were no significant differences observed in the
      levels of plasma IL-1 beta and IL-10 between the preeclamptic and other subject
      groups. The level of IL-1 beta, but not the levels of IL-10, TNF-alpha, or IL-6,
      was significantly changed during normal pregnancy compared with the nonpregnant
      condition manifesting an overall decline (P < 0.04). TNF-beta and IL-1 alpha were
      not detected in any samples, possibly because of the low sensitivity of these
      particular immunoassays. CONCLUSION: Elevated levels of TNF-alpha and IL-6 may
      contribute to the putative endothelial dysfunction of preeclampsia.

PMID- 9764353
TI  - Hepatocyte growth factor in human breast milk.
AB  - PROBLEM: The purposes of this study were to investigate the presence of
      hepatocyte growth factor (HGF) in human milk, to identify the cells that produce
      HGF in human milk, and to determine the contribution of HGF to the growth of
      neonates. METHOD OF STUDY: The HGF concentrations in serum and whey were
      determined with an enzyme-linked immunosorbent assay kit. The presence of HGF in
      whey was also examined by Western blot analysis. To determine which cells in
      human milk produce HGF, an immunohistochemical examination was conducted. The
      expression of HGF mRNA in the mononuclear cells in human milk was examined by
      reverse transcriptase-polymerase chain reaction (RT-PCR). The effects of whey and
      of recombinant HGF (rHGF) on DNA synthesis by a rat small intestinal cell line,
      IEC-6, were examined by [3H]thymidine uptake. RESULTS: Human colostrum whey
      contained 2.22 +/- 1.02 ng of HGF/ml. Milk whey collected 1 month later contained
      1.83 +/- 1.03 ng of HGF/ml. The presence of the heterodimeric form of HGF in
      colostrum whey was demonstrated by Western blot analysis. HGF was detected in the
      cytoplasm of human milk macrophages by an immunohistochemical examination, and
      the RT-PCR also revealed that HGF mRNA is expressed in the mononuclear cells of
      human milk. DNA synthesis by IEC-6 cells was increased by rHGF treatment and by
      whey treatment. The effect of whey on DNA synthesis by IEC-6 cells was partially,
      but significantly, decreased by anti-human HGF-neutralizing antibody treatment.
      CONCLUSIONS: Human milk contains a large amount of the active form of HGF,
      produced by macrophages, and HGF in human milk induces the growth of intestinal
      cells. Our data suggest that HGF in human milk is one of the important factors
      regulating the growth of intestinal cells in neonates after birth.

PMID- 9764354
TI  - How might pregnancy immunize against breast cancer?

PMID- 9764355
TI  - Immunology understood through pregnancy.

PMID- 9764356
TI  - Apoptosis of T cells in the first trimester human decidua.
AB  - PROBLEM: Apoptosis has been accepted as a mechanism for maintaining tolerance in
      the immune system. The induction of apoptotic cell death can also be a possible
      outcome of the lymphocyte activation. Expression of Fas ligand (FasL) by the
      human trophoblast has been proposed as a mechanism providing protection against
      the lytic action of decidual immune cells. The aim of this study was to determine
      whether decidual T cells undergo apoptosis during abortion. METHOD OF STUDY: We
      studied apoptosis of T cells isolated from the first-trimester decidua in 12
      women after spontaneous or elective abortion. We used gel electrophoresis to
      detect DNA fragmentation. Cells undergoing DNA fragmentation also were identified
      by DNA analysis using flow cytometry. This method was based on the accumulation
      of ethanol-fixed apoptotic cells in the sub-G0/G1 peak of the DNA content as a
      result of the loss of DNA fragments from the cells and because of a reduced DNA
      ability to be stained by propidium iodide. In addition, the expression of Fas
      antigen on the surface of decidual T cells (CD3+) also was determined. RESULTS:
      We did not detect apoptosis by the "ladder" technique. However, the apoptotic
      index (the percentage of positive cells per total number of cells) ranged from 2%
      to 24% using flow cytometry. CONCLUSIONS: Trophoblast cells usually fail to
      stimulate alloantigen-specific T cells, but they may express nonclassical major
      histocompatibility complex alloantigens to which mothers can produce
      immunoglobulin G alloantibody, which requires T helper cell activation. The
      apoptosis of T cells in the human decidua, probably through Fas-FasL signaling,
      may be a defense mechanism against rejection of the fetal allograft by the
      maternal immune system.

PMID- 9764357
TI  - Molecular and immunologic aspects of the nonclassical HLA class I antigen HLA-G:
      evidence for an important role in the maternal tolerance of the fetal allograft.
AB  - PROBLEM: Human leukocyte antigen (HLA)-G is a major histocompatibility complex
      class I antigen, which is referred to as nonclassical because it displays a
      tissue-restricted distribution in the placenta, a reduced cytoplasmic domain, a
      limited polymorphism, and several isoforms. The HLA-G antigen is thought to play
      an essential role during pregnancy by protecting the semi-allogeneic fetus from
      recognition and destruction by maternal immune cells. METHOD OF STUDY:
      Alternative splicing of HLA-G mRNA was analyzed by Southern blot of reverse
      transcriptase-polymerase chain reaction products from trophoblasts of the first
      trimester of gestation and term placenta. The regulation of HLA-G gene expression
      was investigated by electrophoretic mobility shift assays using nuclear extracts
      from cells expressing different levels of HLA-G gene activity. Using polymerase
      chain reaction-single strand conformational polymorphism and sequencing, we
      studied HLA-G gene polymorphism in families from the Centre d'Etude du
      Polymorphisme Humain in Paris. To understand the function of the HLA-G molecule,
      cytotoxicity assays were carried out with peripheral blood mononuclear cells or
      polyclonal natural killer effectors cells from 30 different donors against HLA-G1
      and HLA-G2 transfectants. RESULTS: Four main aspects have been elucidated: 1) The
      primary transcript of the HLA-G gene is alternatively spliced into five main mRNA
      forms: HLA-G1 (full length), HLA-G2 (minus exon 3), which encodes a membrane
      bound isoform associated with beta-2 microglobulin, HLA-G3 (minus exons 3 and 4),
      HLA-G4 (minus exon 4), and HLA-G5 (plus intron 4), which encodes a soluble form
      of the HLA-G antigen; 2) specific nuclear factors bind to an important regulatory
      element located more than 1.2 kb from the HLA-G gene. Three specific complexes
      are observed in cells that show HLA-G transcriptional activity and an additional
      factor that could correlate with the repression of HLA-G gene expression that is
      detected in natural killer cells; 3) we observed an important genomic
      polymorphism in exon 3 but a very low polymorphism at the protein level; 4) HLA
      G1 and HLA-G2 transfectants clearly demonstrated that both HLA-G isoforms are
      capable of inhibiting natural killer lytic activity. CONCLUSION: These results
      suggest that HLA-G acts as the public ligand for natural killer inhibitory
      receptors, thus protecting the fetus against maternal rejection.

PMID- 9764358
TI  - HLA-G polymorphisms: ethnic differences and implications for potential molecule
      function.
AB  - PROBLEM: Human leukocyte antigen (HLA)-G is uniquely expressed on extravillous
      cytotrophoblasts of the placenta and is postulated to be a mediator of maternal
      immune tolerance. Although it was originally considered to be nonpolymorphic,
      variations of the HLA-G DNA sequence have been reported, and a limited number of
      HLA-G alleles been defined. METHOD OF STUDY: The HLA-G wild-type sequence was
      compared with HLA-A2 with regard to the conservation of functionally essential
      parts of classical HLA-I molecules. HLA-G polymorphisms were analyzed under the
      aspect of ethnic differences, site, and consequences for postulated molecule
      functions. RESULTS: HLA-G exhibits a high degree of conservation relative to HLA
      A2 in functionally relevant sites of HLA-class I molecules. However, polymorphic
      sites in HLA-G and classical HLA loci are not congruent. CONCLUSION: The type and
      localization of HLA-G polymorphisms suggest that different parts of HLA-G
      molecule underlie different selective constraints.

PMID- 9764359
TI  - Is the expression of classical HLA class I antigens on trophoblast of importance
      for human pregnancy?
AB  - PROBLEM: Human leukocyte antigen (HLA)-C and possibly also HLA-B seem to be
      expressed on the extravillous trophoblast. These antigens carry epitopes that
      function as ligands for natural killer (NK)-cell-inhibitory receptors.
      Antitrophoblast cytotoxicity mediated by decidual NK cells might be involved in
      miscarriage. We thus found it relevant to elucidate whether parental HLA-C and 
      Bw polymorphism play a role in recurrent miscarriage (RM). METHOD OF STUDY: HLA-C
      and -Bw investigations by DNA-based techniques were undertaken in 35 couples with
      unexplained RM and in 30 couples with normal fecundity. The number of HLA-C- and 
      Bw-related supertypic specificities that can bind NK-cell-inhibitory receptors
      was evaluated in selected couples. RESULTS: The proportions of couples with RM
      and control couples carrying four HLA-C alleles with the same NK-cell-inhibitory
      supertypic specificities were equal. In 46% of studied couples with RM, all four
      HLA-B alleles carried the HLA-Bw6 supertypic specificity, which was significantly
      higher than the corresponding frequency (17%) in the control couples (P < 0.02).
      CONCLUSIONS: The expression of polymorphic HLA-C on trophoblasts does not seem to
      play a role in RM. Assuming that HLA-B is expressed on trophoblasts, we may
      suggest that the revealed predominance of HLA-Bw6 expression (which excludes the
      presence of HLA-Bw4-protective antigens) may predispose a particular couple to
      the RM phenomenon.

PMID- 9764360
TI  - Regulation of major histocompatibility complex and TAP gene products in
      preimplantation mouse stage embryos.
AB  - PROBLEM: To determine the ontogeny of major histocompatibility complex (MHC)
      expression and TAP products in mouse embryos. METHOD OF STUDY: mRNAs encoding MHC
      and associated molecules were identified by reverse transcriptase-polymerase
      chain reaction, and the protein products were localized by confocal microscopy.
      RESULTS: mRNAs encoding class Ia (H-2Db) and class Ib (Q7/9) were present in one
      cell embryos, whereas beta 2-microglobulin (beta 2-m) transcripts were not
      detected until the two-cell stage. Transporter TAP1, but not TAP2, transcripts
      were detected only in blastocysts. H-2 class Ia (classical) protein was detected
      on the surface of two-cell embryos, H-2 class Ib (nonclassical) protein was
      detected on one-cell embryos, and beta 2-m transcripts were detected on eight
      cell embryos; TAP1 protein was present at low levels in the cytoplasm from the
      one-cell stage onward, increasing in expression in blastocysts. CONCLUSIONS: In
      mice, MHC class I mRNAs encoding the heavy chain of H-2- and Q7/9-encoding Qa2
      molecules are synthesized soon after conception prior to implantation. Similarly,
      the nonpolymorphic MHC class I-associated molecule beta 2-m also is expressed
      before implantation. TAP1, but not TAP2, is first detected at the blastocyst
      stage, thus preceding the onset of TAP2 in embryonic development.

PMID- 9764361
TI  - Major histocompatibility complex expression on human, male germ cells: a review.
AB  - PROBLEM: The male reproductive compartment is an immunologically privileged site.
      The expression pattern of human leukocyte antigens (HLAs) may play an important
      role in the maintenance of immune tolerance toward differentiating gametogenic
      cells. This review presents current knowledge about HLA gene expression on human,
      male germ cells, on mRNA and protein levels, and on their methylation status.
      METHOD OF STUDY: Different techniques were applied to study HLA gene expression
      in human testis: (a) protein: e.g., cytotoxicity test, fluorescent labeling
      techniques, enzyme-linked immunosorbent assay, and confocal microscopy; (b) mRNA:
      reverse transcriptase-polymerase chain reaction, Northern blot hybridization, and
      in situ hybridization; and (c) methylation status. RESULTS: In normal testicular
      tissue we observe a lack of HLA-class I (classical) antigens expression and
      inversely related expression pattern of HLA class I classical and nonclassical
      genes. HLA-A, -B, -C, and -E loci are likewise methylated in somatic and germ
      cells, whereas -F and -G genes are less methylated in sperm precursors.
      CONCLUSIONS: Immunologic tolerance in human testis is actively maintained by the
      specific expression pattern of HLA genes regulated by hormones and growth
      factors.

PMID- 9764362
TI  - Unique biochemical properties of human leukocyte antigen-E allow for a highly
      specific function in immune recognition.
AB  - PROBLEM: Does a correlation exist between the expression of human leukocyte
      antigen (HLA) class Ia and HLA-E and what is its biological significance? METHOD
      OF STUDY: HLA-E transcripts were detected by reverse transcriptase-polymerase
      chain reaction. Metabolically labeled HLA-E heavy chains were immunoprecipited
      and analyzed by one-dimensional isoelectric focusing. Mouse RMA-S cells defective
      with regard to transporter associated with antigen processing (TAP) function were
      transfected with HLA-E and human beta 2-microglobulin to investigate TAP
      dependence of the cell-surface expression of HLA-E. RESULTS: HLA-E is transcribed
      regardless of the down-regulation of polymorphic HLA class Ia expression. HLA-E
      is transported to the cell surface in the absence of TAP-controlled peptide
      loading. In human cells, the amount of HLA-E protein is very low regardless of
      the presence of correct peptide ligands. CONCLUSIONS: HLA-E regulates immune
      functions in cells that have down-regulated the expression of polymorphic HLA
      class Ia molecules, either by preventing harmful natural killer cells from
      attacking targets that have physiologically decreased HLA-class Ia expression or
      by activating effector cells against virus-infected and tumor cells with impaired
      HLA-class Ia expression.

PMID- 9764363
TI  - Sexual and mother-to-child transmission of the human immunodeficiency virus type
      1: a review.
AB  - PROBLEM: Sexual and mother-to-child transmission of the human immunodeficiency
      virus (HIV) type 1 occurs only with a low percentage of infection. Many instances
      of sexual intercourse result in no transmission, and only 20% of children are
      infected from seropositive mothers (3% in mothers treated with azidothymidine).
      METHOD OF STUDY: We analyzed the presence of HIV in various ejaculates of the
      same HIV-infected patients, as well as in the cervico-vaginal fluid. We have
      studied the mechanism of transmission from mother to child, by analyzing the cell
      to-cell transmission in the trophoblast. RESULTS: Some ejaculates collected at
      different times from the same HIV-infected males are free of virus, explaining
      the low rate of sexual transmission. We never found HIV in mobile spermatozoa.
      The trophoblast can be infected by HIV with a strain dependence and also
      transiently. By analyzing the tissue of the fetus, it was found that only some
      organs are infected, confirming the cell-to-cell transmission between the mother
      and child and not a true vertical transmission through the germinal lines.
      CONCLUSIONS: HIV is not always present in the genital secretion, explaining the
      low rate of sexual transmission. Mother-to-child transmission occurs during
      pregnancy but often after the second trimester and at delivery after cell-to-cell
      or blood transmission, respectively.

PMID- 9764364
TI  - Fertility-disrupting potential of synthetic peptides derived from the beta
      subunit of follicle-stimulating hormone.
AB  - PROBLEM: Hormone immunoneutralization is hampered by immunologic cross-reactivity
      caused by close-sequence homology between related molecules. One solution is to
      use smaller fragments to induce antibodies of greater specificity. METHOD OF
      STUDY: A number of peptides selected from beta-follicle-stimulating hormone (FSH)
      were conjugated to tetanus toxoid and were used to immunize female rats. The
      antisera were examined for FSH cross-reactivity by immunoassays and in an in
      vitro bioassay. RESULTS: In the immunoassays, the antisera did not react with FSH
      but did react with their respective peptides. In the bioassay, sera from
      VYKDPARPC- and CDSLYTYP-immunized animals inhibited FSH-receptor interaction by
      73% and 68%, respectively. These animals also showed reduced estradiol levels.
      Sequences were synthesized around VYKDPARPC and were tested on a FSH-receptor
      bearing Chinese hamster ovary cell line. LVYKDPARPC, VYKDPARPC, YKDPARPIC,
      CLVYKDPARP, and LVYKDPARP inhibited FSH-receptor interaction by greater than 50%.
      In female mice, TRDLVYKDPARPKI and LVYKDPARP disrupted estrous cycling in all
      animals; LVYKDPARPC and CLVYKDPARP disrupted cycling in three of five animals,
      whereas VYKDPARPC disrupted cycling in one of four animals. CONCLUSIONS: Peptides
      from two areas of beta-FSH (VYKDPARP and DSLYTYP) were shown to raise FSH
      neutralizing antibodies, which were able to suppress estradiol levels. An
      additional leucine residue to VYKDPARP greatly enhanced the peptide's ability to
      inhibit FSH-receptor binding and caused fertility disruption in vivo.

PMID- 9764365
TI  - Evaluation of the contraceptive potential of recombinant human ZP3 and human ZP3
      peptides in a primate model: their safety and efficacy.
AB  - PROBLEM: The unique recognition events that result in the avid binding of
      mammalian spermatozoa to the surface of the zona pellucida (ZP) are being
      exploited in the development of contraceptive vaccines. In this study, the safety
      and efficacy of a vaccination strategy based on the induction of active immunity
      against purified, glycosylated, recombinant human ZP3 (rhZP3) has been evaluated
      in a primate model, Callithrix jacchus. METHOD OF STUDY: Long-term infertility
      was established after immunization with rhZP3 and the resulting immune sera
      reacted with rhZP3 on an enzyme-linked immunosorbent assay (ELISA) and
      immunolocalized exclusively to the outer surface of native ZP on marmoset ovarian
      sections. However, this contraceptive effect was inevitably associated with the
      eventual appearance of an ovarian pathology characterized by a depletion of
      primordial follicles. In an attempt to circumvent this side effect, human ZP3
      (hZP3) was epitope mapped and four continuous, immunodominant B-cell epitopes
      (hZP3(45-64), hZP3(93-110), hZP3(172-190) and hZP3(341-360) were evaluated for
      contraceptive efficacy in vivo. Using peptide-tetanus toxoid (TT) conjugates to
      enhance immunogenicity, antipeptide antibodies were raised against these
      immunogens, which also cross-reacted with rhZP3 on ELISA. In addition, antibodies
      against hZP3(45-64) and hZP3(172-190) recognized native ZP on marmoset ovarian
      sections when a microwave technique was used to enhance epitope presentation.
      RESULTS: No ovarian pathology was observed after the long-term administration of
      these peptide immunogens, and fertility was suppressed when compared with TT
      controls but could not be correlated to the antibody titer. CONCLUSION: Clearly,
      further research is required to identify optimal B-cell epitopes that will
      reliably induce infertility, free from any ovarian pathology.

PMID- 9764366
TI  - Epitopes of human chorionic gonadotropin and their relationship to immunogenicity
      and cross-reactivity of beta-chain mutants.
AB  - PROBLEM: Human chrionic gonadotropin (hCG) is a placental glycoprotein hormone, a
      heterodimeric molecule, consisting of alpha and beta chains. It induces the
      synthesis of progesterone, which is essential for the maintenance of the
      fertilized egg. Antibodies directed against hCG can, therefore, prevent pregnancy
      and serve as a vaccine. hCG belongs to the glycoprotein hormone family and shares
      the alpha chain with the other members. The beta chain is a hormone-specific
      subunit that is unique to hCG, but still possesses 85% amino acid homology with
      the beta chain of luteinizing hormone (LH), which means that prolonged
      immunization with hCG produces antibodies that cross-react with LH. METHOD OF
      STUDY: We have taken an approach involving the mutation of beta hCG to eliminate
      cross-reactive epitopes without affecting the natural folding of the polypeptide
      chain and thus the unique beta hCG-specific epitopes. RESULTS: Several mutants
      have been constructed that have maintained the binding to hCG-specific monoclonal
      antibodies (mAbs) but have lost the ability to bind to a panel of LH cross
      reactive mAbs. To investigate the immunogenicity of selected mutants, mice were
      immunized with expression plasmid DNA, containing the gene for wild-type beta hCG
      and two mutants: mutant 3, with four amino acid substitutions (68 Arg-->Glu; 74
      Arg-->Ser; 75 Gly-->His; 79 Val-->His), and mutant 7, with a single amino acid
      substitution (68 Arg-->Glu). CONCLUSIONS: Although both mutants were able to
      elicit antibody responses in at least some animals, the levels were less than
      those seen with the wild-type beta hCG DNA, and there seems still to be a
      residual cross-reactivity with LH. Attempts to improve the immunogenicity of the
      mutants and to further modify the sequence to remove the cross-reactivity are
      currently underway.

PMID- 9764367
TI  - Do autoantibodies to sperm reduce fecundity? A mini-review in historical
      perspective.
AB  - PROBLEM: The paradox that early studies of antisperm antibodies in men showed a
      strong correlation between titers of circulating antibodies (essentially
      immunoglobulin [Ig] G) and reduction in conception rates, whereas more recent
      studies have indicated that the antifertility effect is mainly (or exclusively?)
      associated with IgA antibodies, impairing sperm migration through cervical mucus,
      was studied. METHOD OF STUDY: Relevant literature focusing on antibodies on
      ejaculated sperm was analyzed. RESULTS: Direct mixed antiglobulin reaction (MAR)
      and immunobead-binding tests are excellent and sensitive techniques for
      demonstrating antibodies of the IgG and IgA classes on sperm, and they have
      revealed that IgA antibodies are, with very rare exceptions, found only when IgG
      antibodies are also present. However, these tests tell little about the amounts
      of antibodies present, and attempts to measure quantitatively the amounts of Ig
      on sperm have indicated higher levels of IgA than IgG (despite the strongest MAR
      reactivities for IgG). CONCLUSIONS: The patients with high levels of IgA to their
      sperm are mainly men with strong immune responses and, therefore, also high
      antibody titers in serum. Apparently, the locally produced IgA antibodies reach
      the sperm and occupy the binding sites before the main bulk of IgG reaches the
      seminal compartment with the prostatic fluid.

PMID- 9764368
TI  - Antisperm antibodies in prepubertal boys and their reactivity with antigenic
      determinants on differentiated spermatozoa.
AB  - PROBLEM: Antisperm antibodies induced in prepubertal boys with testicular
      failures were characterized by using four techniques of antibody detection. The
      reactivity of circulating antisperm antibodies in prepubertal boys and the
      reactivity of antibodies in sera samples of adult fertile and infertile males
      were compared against the same sperm antigenic pools (live or fixed spermatozoa,
      or sperm antigenic extracts). METHOD OF STUDY: The incidence of antisperm
      antibodies in sera samples of 69 prepubertal boys with testicular failures and 21
      samples obtained from adult, male individuals was assessed by indirect immunobead
      binding test (IDIBT), flow cytometry measurement, enzyme-linked immunosorbent
      assay, and Western blotting. Immunoblot analysis was performed by using sperm
      extracts of glycosylated and deglycosylated solubilized membrane antigens.
      RESULTS: Sera samples were studied in a group composed of healthy prepubertal
      boys (n = 7) and prepubertal boys with testicular failures (n = 69). Applied
      tests of antibody detection revealed striking differences in a group of boys with
      testicular pathology. With IDIBT, 7% of the sera samples were found positive,
      whereas with flow cytometry measurement, 48% of the sera samples were positive.
      Immunosorbent assay (fixed sperm) indicated 32% positive cases in the same group.
      The sera samples were found to be positive in 65% of immunoblotting reactions
      with glycosylated antigens and in 70% of immunoblotting reactions with
      deglycosylated antigens. All applied detection assays were clearly negative on
      sera samples from fertile, adult males. Western immunoblotting indicated an
      immunodominant antigenic determinant of 58 kDa. CONCLUSIONS: Tests of antibody
      detection with the use of live sperm (IDIBT and flow cytometry measurements)
      presented low sensitivity (8% and 48%, respectively) in a group of prepubertal
      boys. This observation underlines the difficulties in assigning the prospective
      prognosis of future fertility status in prepubertal boys with antisperm
      antibodies.

PMID- 9764369
TI  - The 4 Rs of clinical excellence.

PMID- 9764370
TI  - A question of quality: radiotherapy resources and waiting time outcomes for
      cancer patients.

PMID- 9764371
TI  - The BNLI: past and present. British National Lymphoma Investigation.

PMID- 9764372
TI  - Cancer in developing countries: Part I--Cancer burden, resources, epidemiology,
      aetiology and clinical practice.

PMID- 9764373
TI  - Dosimetry rules for brachytherapy using high dose rate remote afterloading
      implants.
AB  - The increasing availability of high dose rate (HDR) afterloading units has
      highlighted the potential use of this form of brachytherapy in an ever wider
      number of clinical sites. Alongside this, commercial planning systems for
      brachytherapy offer almost infinite possibilities for the differential loading of
      applicators in an attempt to produce an ideal dose distribution. Dosimetry in the
      UK has been based largely on the Manchester and Paris systems; modifications and
      optimization of the Paris system in HDR brachytherapy have been proposed, but the
      Manchester dosimetry system, with its emphasis on dose homogeneity throughout the
      specified treatment plane or specified treatment volume, can also be successfully
      applied, unmodified, in HDR dosimetry. A comparison of Manchester, Paris and
      optimized distributions for an HDR implant is presented, illustrating how
      subjectively and on the basis of dose-volume histograms, optimization has in this
      clinical case failed to improve on the uniformity of the Manchester rules
      distribution. It is proposed that optimization systems should have an option to
      apply these rules with further individualized clinical optimization if required.
      This would permit uniform reporting of implant parameters where, by describing
      the clinical target volume, the total reference air kerma and initial
      distribution of dwell times will be defined.

PMID- 9764374
TI  - Technical hints for high dose rate interstitial tongue brachytherapy.
AB  - High dose rate (HDR) interstitial tongue brachytherapy is a new treatment
      modality. This study describes important technical details required for its
      successful use. Thirteen patients with carcinoma of the oral tongue were treated
      solely with interstitial brachytherapy using HDR remote afterloading techniques
      during the years 1994-1997. The afterloading catheters were positioned by the
      submandibular approach with the assistance of a template set. Custom-made
      mandibular lead shields were inserted prior to treatment. Special reusable Tuen
      Mun Hospital (TMH) lead buttons were made for improved radiation protection. The
      median dose given was 55 Gy in ten fractions over 6 days. The interfraction
      interval was 7 hours for the first seven patients treated and was extended to 8
      hours for the other six. Shrinking field techniques were employed and the
      treatment length of the last fraction was reduced by 5 mm. Commencing with the
      second patient treated with double planar implants, the medial plane was treated
      with eight fractions while the lateral plane received ten fractions. To reduce
      further the potential risk of tract seeding, additional coverage to the
      implantation tracts was given for the last four patients, with the resultant
      isodose curves resembling a 'comb rake/brush'. The mean and median measured doses
      on the inner face of the mandibular shields were 113% and 93% of the reference
      dose respectively (range 77-247). The dose to the corresponding sites on the
      gingival surface can be reduced by 75% if the 3 mm thick lead shield is placed
      successfully. With the use of the TMH button, the transmitted dose to the tissue
      in direct contact can be reduced by one-third. With the 'comb rake/brush' dose
      distribution, the high dose volume of the single planar implants could be reduced
      by 44%, compared with the low dose rate technique, if loading to just 5 mm short
      of the submandibular skin was required. The mean doses for the combination of
      eight double planar plus two single planar implants, and ten double planar
      implants, are on average 29% and 37% greater than the reference dose
      respectively. An 8% reduction in absolute dose in the region between the planes
      of the catheters would lead to an even greater magnitude of reduction in
      morbidity to late responding tissue. The prerequisite for the success of HDR
      interstitial implants is to develop a good technique in positioning the
      afterloading catheters and protection of the normal tissue. Its importance merits
      special attention if HDR remote afterloading interstitial tongue brachytherapy is
      to realize its full potential.

PMID- 9764375
TI  - The management and clinical course of testicular seminoma: 15 years' experience
      at a single institution.
AB  - Testicular seminoma is one of the most curable solid neoplasms, with 5-year
      survival rates in excess of 90%. However, controversy persists around its optimum
      management, particularly for Stage I disease. The outcome of 314 patients with
      testicular seminoma who were treated at a single institution is reported. A
      comparison of adjuvant radiotherapy and surveillance for Stage I is presented,
      and the possible prognostic influence of an elevated serum beta-human chorionic
      gonadotrophin (beta hCG) is assessed. The 5-year disease-free survival for all
      stages of presentation was 95.5%. There were more relapses in Stage I patients
      undergoing surveillance (14/94, 15%) than postorchidectomy radiotherapy (6/144,
      4%; P = < 0.05). However, survival was identical irrespective of treatment
      policy, with no disease-related deaths in either group of Stage I patients. There
      were eight tumour-related deaths from advanced disease and 14 deaths from non
      tumour causes. Three were due to cardiorespiratory disease, four to an unrelated
      second malignancy, two from infection and one from suicide; in four patients, the
      cause was unknown. Preoperative beta hCG was elevated in 29 (18%) of Stage I
      patients and in 24 (62%) of those presenting with Stage II disease. Patients were
      more likely to have advanced disease (> or = Stage II) if beta hCG was elevated
      (P < 0.001). Neither disease-free nor overall survival were influenced by the
      preoperative level of beta hCG. Surveillance appears to be a safe alternative to
      postorchidectomy radiotherapy for Stage I disease, provided the patient is
      prepared for intensive long term follow-up. An increased risk of relapse, but not
      of tumour death, can be expected and unnecessary treatments avoided.

PMID- 9764376
TI  - Granulosa cell tumours of the ovary: demographics, survival and the management of
      advanced disease.
AB  - Ovarian granulosa cell tumours (OGCT) are rare, accounting for only 3%-5% of
      primary ovarian tumours. As a result of oestrogen production OGCTs tend to
      present with early stage disease, which has a good prognosis. For patients with
      advanced disease, surgery and radiotherapy have been the major modalities of
      treatment. More recently, platinum-based chemotherapy has been shown to have
      important activity in advanced disease. In this retrospective study, we have
      reviewed the results of 62 patients who were treated for adult OGCT at the Royal
      Marsden Hospital between 1969 and 1995, with particular emphasis on the
      management of advanced disease. The median age at primary diagnosis was 53 years
      (range 13-77). Sixty-one per cent of these patients had Stage I disease, 21%
      Stage II disease, 16% Stage III and 2% Stage IV. Stage I patients had a good
      prognosis with 5- and 10-year overall survival rates of 95% and 90%. Eleven Stage
      I patients received adjuvant pelvic radiotherapy, with no apparent benefit to
      recurrent rate or overall survival. Disease progression occurred in 40% of Stage
      I patients at a median interval of 76 months (range 12-240), and in 62% of the
      Stage II patients, at a median interval of 31 months (range 2-57). The median
      interval from progression of Stage I/II disease to death was 22 months (range 3
      144). For patients with inoperable disease, radiotherapy produced a number of
      long-term remissions with an overall response rate of 50%. Platinum-based
      chemotherapy also appears active, with responses documented in four out of five
      patients treated with the PVB regimen (cisplatin, vinblastine, bleomycin) as
      first line therapy. There were no responses documented to non-platinum
      chemotherapy or to hormonal manipulation. The results from this study confirm the
      activity of platinum-containing chemotherapy regimens in OGCT and support the
      need for further trials to optimize the management of this rare tumour.

PMID- 9764377
TI  - Malignant mixed mullerian tumours of gynaecological origin: chemosensitive but
      aggressive tumours.
AB  - We report the clinical management and outcome of 11 patients with a histological
      diagnosis of mixed mullerian tumour of gynaecological origin who were treated at
      Weston Park Hospital, Sheffield during the period 1991 to 1996. Case note review
      provided the data on the patients, their disease and the treatment given. In six
      patients, the primary site was the ovary and in four it was the uterus; in the
      remaining patient, the tissue of primary origin was uncertain. The median age at
      diagnosis was 53 years (range 48-84). Seven patients had heterologous tumour
      histology. All but one underwent surgical removal or debulking of disease. Seven
      patients were treated with platinum-based chemotherapy. There were four complete
      responders and three partial responders. The median survival was 18 months. Three
      patients remain alive, two of them disease-free. Mixed mullerian tumours are
      initially chemosensitive but have an aggressive clinical course, typically with
      early relapse after treatment and a poor long-term prognosis. Collaborative Phase
      III studies are required to improve the management of this uncommon cancer.

PMID- 9764378
TI  - Somnolence syndrome in adults following cranial irradiation for primary brain
      tumours.
AB  - The purpose of this study was to assess the incidence, pattern and severity of
      somnolence and fatigue in patients treated with cranial irradiation for primary
      brain tumours and to identify factors that may influence or mediate symptoms. A
      detailed prospective study was carried out of 19 patients who received high-dose
      (45-55 Gy) cranial irradiation as treatment for primary brain tumours. Data were
      collected for each patient over a 3 month period using a prospective diary
      utilizing visual analogue scales of common somnolence symptoms and fatigue, and
      detailed interviews at 2, 6 and 12 weeks following the completion of treatment.
      Sixteen patients developed somnolence syndrome following treatment. Time series
      analysis identified a cyclical pattern to the symptoms, with a period of
      drowsiness and fatigue occurring from day 11 to day 21 and from day 31 to day 35
      after radiotherapy. The principal symptoms were those of excessive drowsiness,
      feeling clumsy, an inability to concentrate, lethargy, being mentally slow and
      fatigue. Patients treated with accelerated (n = 11) compared with more
      conventional (n = 8) fractionation experienced more severe drowsiness and fatigue
      (P < 0.01), although there was no difference in the pattern or the incidence of
      symptoms. Interview data suggested that patients frequently attributed their
      symptoms of somnolence to 'flu or other ailments. The unexplained and
      overwhelming nature of the symptoms was a cause of anxiety. The prospective
      assessment of symptoms following radiotherapy highlighted a more detailed
      definition of the symptom complex and pattern of occurrence. Somnolence syndrome
      is a collection of symptoms consisting of drowsiness, lethargy and fatigue.
      Forewarning patients and planning supportive management around times of
      drowsiness and fatigue can help to reduce the anxiety that these symptoms cause.

PMID- 9764379
TI  - The importance of cytogenetics and associated molecular techniques in the
      management of patients with leukaemia.
AB  - The cytogenetic analysis of haematological malignancies plays a major role in
      diagnosis. A large number of non-random chromosomal abnormalities are associated
      with specific types of leukaemia. Often, the cytogenetic result provides the
      definitive diagnosis. The recent developments in molecular cytogenetic
      technologies, in association with conventional cytogenetic analysis, have
      improved the accuracy of the results and led to the finding of new chromosomal
      abnormalities in leukaemia. Patients may be monitored by cytogenetics, molecular
      techniques and/or fluorescence in situ hybridization (FISH) during the course of
      their management, for evidence of minimal residual disease. These techniques also
      provide a useful method for monitoring patients following bone marrow
      transplantation, particularly when the patient and the donor are of the opposite
      sex. The cytogenetic result is an independent prognostic indicator, with certain
      karyotypes associated with a good prognosis, although others indicate a poor
      outcome.

PMID- 9764380
TI  - An audit and evaluation of bladder movements during radical radiotherapy.
AB  - With the introduction of the conformal approach for radical radiotherapy for
      prostate cancer, there has been renewed interest in the movement of the prostate
      and other pelvic organs during the course of radical pelvic radiotherapy. Many
      patients reviewed during a course of radical radiotherapy for bladder carcinoma
      have urinary flow symptoms, which may suggest impaired bladder emptying. There is
      concern, therefore, that the bladder volume may increase during such treatment,
      leading to inadequate coverage of the bladder by the planning target volume. We
      used serial CT scans to assess bladder size in 20 patients during the course of
      radical bladder radiotherapy. Our results showed that there was little variation
      in the left to right direction and, in 12 of the 20 patients studied, the
      anteriorposterior (AP) movement was < 1 cm. The bladder dome rose out of the
      treatment field in two patients during the course of therapy. However, in 16
      patients, the target volume was encompassed as planned throughout.

PMID- 9764381
TI  - Low grade MALT lymphoma of the urinary bladder.
AB  - Primary lymphoma of the bladder is rare. Of the very few cases reported, most
      appear to be of low grade with a generally good prognosis. Since the concept of
      low grade lymphoma of mucosa associated lymphoid tissue (also known as marginal
      zone lymphoma in the REAL classification) was introduced, only six examples of
      this entity have been recorded at this site. We present a further case and
      describe its phenotypic characterization.

PMID- 9764382
TI  - Death due to thyroid metastases from renal cell carcinoma.
AB  - Renal cell carcinoma is a tumour that is well recognized to metastasize widely
      and to behave in an unpredictable manner. We report a patient with a renal cell
      carcinoma that metastasized to the thyroid and resulted in death from associated
      respiratory compromise. The clinical features of cancers metastasizing to the
      thyroid are discussed and the apparent over-representation of renal cell
      carcinoma in symptomatic thyroid metastases is highlighted. The uncertainty about
      whether metastases arise more frequently in pre-existing abnormal thyroid glands
      is also reviewed.

PMID- 9764383
TI  - Severe hypertriglyceridaemia and hypercholesterolaemia associated with tamoxifen
      use.
AB  - A patient who was given tamoxifen as adjuvant treatment for breast cancer
      developed very severe hypertriglyceridaemia, hypercholesterolaemia and acute
      pancreatitis after being treated for 4 months. The hyperlipidaemia was corrected
      after cessation of the tamoxifen and the institution of gemfibrozil treatment.
      This patient appears to have type IV hyperlipidaemia. It is suggested that, in
      such patients, tamoxifen should be used with extreme caution because the weakly
      oestrogenic effect of this agent can cause severe and life threatening
      hyperlipidaemia.

PMID- 9764384
TI  - Massive lethal cerebral bleeding in a patient with melanoma without intracranial
      metastasis.
AB  - The case history is reported of a patient with melanoma and advanced metastases,
      who died from massive cerebral bleeding. The lethal event was not caused by
      intracerebral metastasis but by thrombocytopenia. Depression of the bone marrow
      resulted from tumour infiltration of the skeleton, chemotherapy and vertebral
      irradiation. An increase of intracranial pressure triggered the cerebral
      bleeding, caused by haematemesis from a gastric metastasis directly preceding
      sudden somnolence.

PMID- 9764385
TI  - Acute stroke following cisplatin therapy.
AB  - Cisplatin is a very effective drug in modern chemotherapy practice. It has many
      side effects, including neurotoxicity, and has been tentatively implicated in
      acute stroke. We describe a 21-year-old woman who presented with an acute stroke,
      confirmed on MRI as a cerebral infarction.

PMID- 9764386
TI  - Second opinions in oncology: nuisance or opportunity?

PMID- 9764387
TI  - Detection of enterotoxigenic Escherichia coli in stool specimens by polymerase
      chain reaction.
AB  - A polymerase chain reaction (PCR) protocol for rapid (7 h) detection of
      enterotoxigenic Escherichia coli (ETEC) is described. This protocol has been
      validated on 57 stool samples from young children by comparing it with the colony
      hybridization technique. A good agreement was found between the two methods with
      Cohen's kappa statistics of 0.87 and 0.79 for the detection of the heat-stable
      toxin (ST) and heat-labile toxin (LT), respectively. Of 26 samples positive for
      LT and 15 samples positive for ST by colony hybridization, 21 (81%) and 15 (100%)
      were also found to be positive for LT and ST by PCR, respectively. Only one
      sample identified as LT-negative by colony hybridization was found to be positive
      by PCR. However, 3 of 42 samples of ST-negative by colony hybridization were
      detected as positive by PCR. A reconstruction experiment revealed that PCR could
      detect LT-producing and ST-producing ETEC at minimal concentrations of 2.5 x
      10(3) cfu and 2.5 x 10(2) cfu per gram of feces, respectively. These data
      indicate the possible use of this method for rapid identification of ETEC
      associated diarrhea in clinical and epidemiological settings.

PMID- 9764388
TI  - Molecular epidemiology of penicillin-resistant Streptococcus pneumoniae isolated
      in central Taiwan.
AB  - Previous studies have suggested that penicillin-resistant pneumococcal isolates
      (especially those with MIC > 1 microgram/mL) usually are clonally related. To
      test this hypothesis, the molecular epidemiology of 29 clinical isolates of
      penicillin-resistant pneumococci (of which 83% were also resistant to either
      cefotaxime or ceftriaxone) collected in central Taiwan was investigated by pulsed
      field gel electrophoresis. Twenty-seven distinct patterns were identified. Our
      results indicate that an increase in penicillin-resistant S. pneumoniae between
      April 1993 and June 1994 in central Taiwan is not due to the clonal dissemination
      of a limited number of epidemic strains.

PMID- 9764389
TI  - The rationale and method for constructing internal control DNA used in pertussis
      polymerase chain reaction.
AB  - The inclusion of an appropriate internal control DNA in polymerase chain reaction
      (PCR) is a rapid and simple method for the detection of PCR failure. Two PCR
      coamplification internal control DNAs (ICD I and ICD II) with the same primer
      binding sequences as the target DNA for the detection of Bordetella pertussis and
      Bordetella parapertussis were produced using an overlap extension technique and a
      PCR MIMIC construction kit, respectively. The ICD II was further evaluated in a
      prospective clinical study in 360 patients with a clinical diagnosis of
      pertussis. From 360 nasopharyngeal swabs the internal control was positive in 318
      (88%) samples, but was negative in 42 (12%). After phenol-chloroform extraction
      an additional 10 internal controls became positive. For the detection of PCR
      failure, the use of internal control DNA is highly recommended for PCR-based
      identification of B. pertussis and B. parapertussis organisms from nasopharyngeal
      swabs and aspirates.

PMID- 9764390
TI  - Colonization and microbiology of the motile enterococci in a patient population.
AB  - The motile enterococci with the vanC gene have intrinsic low-level resistance to
      vancomycin, but have not been implicated in a nosocomial outbreak. We determined
      the colonization rate of motile enterococci in hospitalized and nonhospitalized
      patients. Perianal or stool specimens were cultured in Enterococcosel broth
      supplemented with 6 micrograms of vancomycin per mL. Rapid motility and pigment
      tests were performed on all enterococci isolated. A total of 82 motile and/or
      pigmented enterococci were isolated from 679 patients for a colonization rate of
      12.1%. There were 43 Enterococcus gallinarum, 32 Enterococcus casseliflavus, 4
      Enterococcus flavescens, and 3 Enterococcus mundtii identified. The E. gallinarum
      vancomycin MIC90 was 32 micrograms/mL and the E. casseliflavus vancomycin MIC90
      was 8 micrograms/mL.

PMID- 9764391
TI  - Detection and characterization of Helicobacter pylori from patients with
      gastroduodenal diseases.
AB  - Polymerase chain reaction and cytotoxin assays were performed to identify as
      Helicobacter pylori type I (cagA+/tox+) or type II (cagA-/tox-) 56 (59.6%)
      strains from 94 patients. Of these patients 64 were affected by nonulcer
      dyspepsia (NUD), 10 by gastric ulcer (GU), 19 by duodenal ulcer (DU), and 1 by
      both GU and DU. H. pylori strains were tested for cagA using two sets of primers;
      target sequences were detected in 40-42/56 (71.4-75%) depending on the set of
      primers used, while cytotoxin-producing strains (tox +) were 26/56 (46.4%). Tox+
      strains were isolated in 13/32 (40.6%), 2/7 (28.6%), and 11/17 (64.7%) in NUD,
      GU, and DU patients, respectively. However, the different percentage between
      cagA+ strains from NUD patients (13/32; 40.6%) and patients with ulcerative
      diseases (13/23; 54.2%) is not statistically significant (p = 0.462). Because the
      two sets of primers employed for amplification of cagA target sequences give
      different results, we concluded that cagA alone could not be taken as predictive
      factor for severity of gastroduodenal disease. It has been found that H. pylori
      type I is associated with duodenal ulcer disease.

PMID- 9764392
TI  - Comparison of algorithms for selective use of nucleic-acid probes for
      identification of Mycobacterium tuberculosis from BACTEC 12B bottles.
AB  - We retrospectively compared the sensitivity of two approaches, a time-to
      detection algorithm and the presence of serpentine cords of acid-fast bacilli,
      for discriminating between BACTEC 12B cultures containing either Mycobacterium
      tuberculosis complex (MTB) or Mycobacterium avium complex (MAC). From January
      1996 through March 1997 a total of 217 of 2089 respiratory specimens received in
      our laboratory were positive in the BACTEC 12B radiometric culture system for
      either MTB (120 specimens) or MAC (97 specimens). Use of a previously published
      time-to-positivity algorithm would have resulted in the correct use of the MTB
      probe on 109 of 120 cultures (91% sensitivity), and the MAC probe on 52 of 97
      cultures (54% sensitivity). The presence of serpentine cords was detected in 58
      of 120 cultures containing MTB (48%), and in 3 of 97 (3%) cultures containing
      MAC. Using a combination of time to positivity and cord formation to determine
      initial probe selection would have resulted in first use of the MTB probe in 116
      of 120 (97%) instances in which MTB was present in the culture. In only 49 of 97
      (51%) cultures, however, from which MAC was recovered would the correct probe
      have been selected. These results indicate that limiting the initial use of the
      MTB probe to those cultures that are either identified by the time-to-detection
      algorithm or demonstrate serpentine cords on acid-fast smear would eliminate a
      considerable amount of unnecessary probe use without compromising the efficiency
      of identification of isolates of MTB.

PMID- 9764393
TI  - Multisite reproducibility of MIC results by the Sensititre YeastOne colorimetric
      antifungal susceptibility panel.
AB  - Reproducibility of MIC results between laboratories, a major performance
      criterion used for evaluation of any susceptibility test method, was determined
      at three test sites using the Sensititre YeastOne Antifungal Panel, which
      incorporates Alamar Blue as a colorimetric indicator. MICs of five antifungals
      were determined using a set of 10 isolates of Candida species. Each isolate was
      tested a total of nine times against each antifungal agent in each of the three
      laboratories. A total of 1350 MICs were evaluated. MICs were read visually after
      incubation at 35 degrees C for 24 and 48 h. Overall, 99 to 100% of MIC values
      were encompassed by a range defined by the modal MIC +/- 1 dilution for each
      antifungal agent tested at both 24 h and 48 h. Replicate testing of the quality
      control isolates recommended by the National Committee for Clinical Laboratory
      Standards demonstrated excellent agreement between results obtained with the
      Sensititre YeastOne panel and the MIC reference range for each antifungal agent.
      These studies demonstrated that the Sensititre YeastOne Antifungal Panel may be
      used to generate MIC values for at least five different antifungal agents with a
      high degree of intra- and interlaboratory reproducibility.

PMID- 9764394
TI  - Detection of Epstein-Barr virus-specific antibodies by an automated enzyme
      immunoassay. Performance evaluation and cost analysis.
AB  - Detection of antibodies to specific antigens of Epstein-Barr virus (EBV) has been
      conventionally performed by an immunofluorescence assay (IFA). The procedure is
      labor intensive and expensive, and interpretation of results is subjective. We
      evaluated an automated enzyme immunoassay (EIA) (INC-STAR Corp., Stillwater, MN,
      USA) using 290 serum specimens submitted for the diagnosis of acute infection
      with EBV. Antibodies (IgG, IgM) to EBV capsid antigen and IgG class antibodies to
      the nuclear antigen of the virus were obtained using the LABOTECH Automated
      Microplate Analyzer (BioChem ImmunoSystems Inc., Allentown, PA, USA) and were
      compared to the antibody profile results obtained by IFA and Western blot as the
      "gold standard." For detection of acute infection with EBV (presence of IgM and
      IgG antibodies to the capsid antigen; absence of antibodies to the nuclear
      antigen), the EIA had 100% sensitivity (11 of 11) and 99% specificity (275 of
      279) compared to IFA and Western blot results. A cost analysis of IFA and EIA
      procedures, based on an estimated annual volume of 12,000 procedures, indicated
      that $236,000 direct cost and 1,400 h technologist time could be saved with the
      automated compared with immunofluorescence procedure. The automated EIA for
      determination of antibodies provides cost-effective, accurate diagnosis of EBV
      infections in laboratories processing high numbers of specimens now processed by
      IFA.

PMID- 9764395
TI  - Enhancement of varicella-zoster virus detection in A-549 shell vials by use of
      freeze-thawed specimens, extended incubation, and "a centrifuged, not incubated"
      direct detection method.
AB  - A total of 95 clinical samples were cultured for periods of 2 and 7 days in
      centrifuged A-549 shell vials before and after freezing and thawing of specimens.
      In addition, centrifuged A-549 shell vials were tested directly for varicella
      zoster virus without incubation using a direct fluorescent antibody (DFA)
      technique. Twenty-seven specimens were positive by at least one method. The
      sensitivity for DFA on unincubated A-549 shell vials was 85.2%; for unfrozen 2
      day cultures, 88.9%; for unfrozen 7-day cultures, 92.6%; for freeze-thaw 2-day
      cultures, 92.6%; and for freeze-thaw 7-day cultures, 96.3%. Freeze-thawed
      specimens cultured for 7 days yielded the highest number of positive results with
      conspicuous cell-to-cell spread as a sign of viral replication.

PMID- 9764396
TI  - Emphysematous prostatic abscess due to Klebsiella pneumoniae.
AB  - Prostatic abscess is an unusual occurrence in the era of modern antibiotics. We
      report a rare case of emphysematous prostatic abscess owing to Klebsiella
      pneumoniae in a 45-year-old man with a 10-year history of alcoholism and a 6-year
      history of diabetes mellitus. Prostatic abscess is a difficult clinical diagnosis
      without specific symptoms and signs. Computerized tomography can assist in making
      the diagnosis of emphysematous prostatic abscess. Definitive treatment is
      complete surgical drainage and the use of effective antibiotics.

PMID- 9764397
TI  - European Glycopeptide Susceptibility Survey of gram-positive bacteria for 1995.
      European Glycopeptide Resistance Survey Study Group.
AB  - In the European Glycopeptide Susceptibility Survey 7078 Gram-positive isolates
      collected in 1995 from 70 centers in 9 countries of Western Europe were examined,
      using a standardized, quantitative susceptibility testing method. Of the 7078
      isolates, 6824 (96.4%) were tested by the national coordinating centers.
      Teicoplanin (mode MIC 0.5 microgram/mL) was generally twice as active as
      vancomycin (mode MIC 1 microgram/mL) against Staphylococcus aureus (n = 2852).
      All isolates were susceptible to vancomycin (MIC < or = 4 micrograms/mL) and all
      but four to teicoplanin (MIC < or = 8 micrograms/mL); these four isolates were of
      intermediate susceptibility (MIC 16 micrograms/mL). With coagulase-negative
      staphylococci (n = 1444), the distribution of MIC of teicoplanin was wider than
      for vancomycin. Two and two-tenths percent of coagulase-negative staphylococci
      excluding Staphylococcus haemolyticus required 16 micrograms/mL teicoplanin for
      inhibition (intermediate) and 0.4% > or = 32 micrograms/mL (resistant). Among
      isolates of S. haemolyticus, 4.4% were of intermediate susceptibility (MIC 16
      micrograms/mL) and 3.3% were resistant (MIC > or = 32 micrograms/mL) to
      teicoplanin. However, this species represented only 6.3% of the isolates of
      coagulase-negative Staphylococcus spp. Generally, teicoplanin (mode MIC < or =
      0.12 microgram/mL) was four to eight times more active than vancomycin (mode MIC
      < or = 0.5 microgram/mL) against the 770 streptococcal isolates. Glycopeptide
      susceptible Enterococcus spp. (n = 1695) were generally four times more
      susceptible to teicoplanin (mode MIC 0.25 microgram/mL) than to vancomycin (mode
      MIC 1 microgram/mL). Combined vancomycin and teicoplanin (VanA phenotype)
      resistance was observed more frequently (9.3%) in isolates of Enterococcus
      faecium than in Enterococcus faecalis (0.8%). Four isolates of unspeciated
      enterococci (1.4%) also expressed this resistance phenotype. Four isolates of E.
      faecium and four of E. faecalis expressed the VanB-type (low-level, vancomycin
      only) resistance. Spain was the only country not to submit resistant E. faecium
      strains while resistant E. faecalis isolates came only from Spain and Italy.

PMID- 9764398
TI  - In vitro evaluation of a novel orally administered cephalosporin (Cefditoren)
      tested against 1249 recent clinical isolates of Haemophilus influenzae, Moraxella
      catarrhalis, and Streptococcus pneumoniae.
AB  - Cefditoren (formerly ME-1206), a new orally administered cephalosporin, was
      evaluated in vitro against 1249 recently isolated strains of Streptococcus
      pneumoniae (500 strains), Moraxella catarrhalis (250 strains), and Haemophilus
      influenzae (499 strains). Reference National Committee for Clinical Laboratory
      Standards methods were used and the strains were representative for the current
      rates of beta-lactamase production or penicillin resistance. Cefditoren had
      MIC50/MIC90 results for Moraxella catarrhalis and Haemophilus influenzae of
      0.12/0.5 and < or = 0.008/0.015 microgram/mL, respectively. The pneumococci were
      consistently twofold to eightfold more susceptible to cefditoren than other oral
      cephalosporins or penicillins. The MIC90 for penicillin-resistant S. pneumoniae
      was only 2 micrograms cefditoren/mL, and the highest recorded MIC was 4
      micrograms/mL. Cefditoren appears to be a very promising beta-lactam possessing
      the greatest potency and potential spectrum versus contemporary (1997)
      respiratory tract pathogens.

PMID- 9764399
TI  - Properties and functions of feline herpesvirus type 1 glycoproteins.
AB  - Feline herpesvirus type 1 (FHV-1) is a causative agent of feline viral
      rhinotracheitis and belongs to the subfamily Alphaherpesvirinae of the family
      Herpesviridae. Since first isolated in 1958 by Crandell and Maurer, FHV-1 is
      distributed worldwide and is the most clinically significant agent for
      respiratory infections in cats. In this review, we describe the recent findings
      with properties and functions of FHV-1 glycoproteins, especially hemagglutinins.

PMID- 9764400
TI  - Cytotoxicity induced by recombinant human tumor necrosis factor-alpha dependent
      on the types of its receptors on canine cells.
AB  - Based on the recent findings that show how recombinant human tumor necrosis
      factor (rh-TNF)-alpha has potent antitumor activity on human cancer patients when
      it locally administrated, we have tested the cytotoxicity of rh-TNF-alpha on 3
      canine cultured cells: (1) canine kidney carcinoma (CKCa-1), (2) mastocytoma and
      (3) Mardin Darby canine kidney cells (MDCK). The cell surface expression of TNF
      alpha receptors on these canine cells was also determined with anti-human TNF RI
      and RII polyclonal antibodies. Our data shows that on CKCa-1 which has TNF RI
      receptors rh-TNF-alpha induced cytotoxicity. By contrast, it exhibited no
      toxicity on canine mastocytoma which has mainly RII receptors. The data also
      suggest actinomycin D (ACT-D), an anticancer antibiotic, enhanced the
      cytotoxicity of rh-TNF-alpha. Combined with ACT-D, rh-TNF-alpha showed the
      cytotoxicity on MDCK which possessed both TNF RI and RII receptors. The results
      indicate that the cytotoxicity of rh-TNF-alpha depends on the presence of TNF RI
      receptors on canine tumor cells.

PMID- 9764401
TI  - Morphological analysis of olfactory receptor cells using whole-mount preparations
      of the rat nasal mucosa.
AB  - The distribution and entire shape of olfactory receptor cells were investigated
      by means of whole-mount preparations of the nasal mucosa. Whole mucosa isolated
      from the nasal septum of rats was processed, as "a free-floating section", and
      examined by the avidin-biotin complex (ABC) method using antisera against protein
      gene product 9.5 (PGP 9.5) and calbindin. Essentially all receptor cells were
      immunolabeled with the PGP 9.5 antiserum, but only half of PGP 9.5-immunoreactive
      cells were calbindin-immunoreactive. In the immunostaining of whole-mount
      preparations, pretreatment of tissues by freeze-thawing and dipping in ethanol
      and xylene greatly improved the permeability of antibodies. Overview of the nasal
      septum showed that the dorsal and ventral portions of the rostral olfactory area
      extended deeply into the respiratory area, making a "semi-lunar" shape. The
      boundary between the two areas was clearly demarcated, although several receptor
      cells were scattered in the respiratory area near the boundary. Observation at
      higher magnification clearly demonstrated that several axons derived from
      perikarya gathered to form nerve bundles showing a dendritic pattern. Proximal
      axons close to perikarya displayed beaded structures with intense
      immunoreactivity. They were electron-microscopically identified as swollen
      portions of axons which might be formed in association with the axonal flow. The
      present study showed that whole-mount preparation of the nasal mucosa for
      immunohistochemistry is a useful tool to analyze the morphology of olfactory
      receptor cells and axons.

PMID- 9764402
TI  - Influence of cell surface glycoprotein gC produced by pseudorabies virus on
      cytopathic effect.
AB  - The wild-type pseudorabies virus (WT-PRV) produced a round-type cytopathic effect
      (CPE) in PK-15 cell line of porcine kidney origin, while PRVgCs lacking in gC
      transmembrane-anchor region and PRVgC-defecting in gC gene produced a syncytium
      type CPE. The mouse embryo cell line (BALB/3T3 clone A31) were transfected with
      recombinant plasmid of pcDNA3 which incorporated with gC gene. The transfected
      A31/gC cells were stably expressing gC. Only a round-type CPE was observed in
      these cells infected with WT-PRV, while a syncytium-type CPE was observed in the
      cells infected with each of the PRVgCs and PRVgC-. Any viruses described above
      induced a syncytium-type CPE in A31/pcDNA cells transfected with a plasmid
      without gC gene. By WT-PRV infection, PK-15 cells generated about 2- or 8-fold
      more gC than the A31/gC and A31/pcDNA cells when gC was measured by
      hemagglutination test. Flowcytometric analysis revealed that amount of gC on the
      cell surface of A31/gC and PK-15 cells increased after infection with WT-PRV.
      Round-type CPE was observed with the increase of gC. These results suggest that
      the type of CPE formation induced by PRV is dominated by the amount of gC on the
      infected cell surface.

PMID- 9764403
TI  - Clinical effects of the recombinant feline interferon-omega on experimental
      parvovirus infection in beagle dogs.
AB  - The clinical effects of recombinant feline interferon-omega (rFeIFN-omega),
      produced in silkworm by recombinant baculovirus, were examined in 3-4 month-old
      beagle dogs given an experimental canine parvovirus type-2 (CPV-2) infection.
      Clinical symptoms, such as pyrexia, vomiting, anorexia and diarrhea, were
      observed on day 4 after oral inoculation of 10(7) TCID50 of CPV-2 (cc 238 strain)
      in almost all the inoculated dogs. From day 4, rFeIFN-omega (1 mega units/kg/day)
      or physiological saline was administered intravenously to infected dogs for 3
      consecutive days. Seven out of 17 dogs treated with physiological saline showed
      hemorrhagic diarrhea and continuously expressed severe clinical enteritis; one
      dog died with a large amount of hemorrhagic rice-water stool on day 6 after viral
      exposure. In contrast, 4 out of 12 dogs treated with rFeIFN-omega showed severe
      clinical enteritis associated with intermittent diarrhea. Scoring of fecal
      condition revealed that treatment with rFeIFN-omega significantly shifted the
      enteritis from a severe to mild form. Furthermore, rFeIFN-omega administered in
      the morning decreased the number of dogs expressing clinical enteritis in the
      evening suggesting a rapid effect. Vomiting and anorexia were also improved by
      treatment with rFeIFN-omega. These results suggest that rFeIFN-omega can reduce
      severe enteritis caused by CPV-2 infection in dogs.

PMID- 9764404
TI  - Genetic characterization of parainfluenza virus 3 derived from guinea pigs.
AB  - To understand the relationship between novel parainfluenza virus 3 (PIV-3), which
      has recently been isolated from the lungs of guinea pigs, and other PIV-3
      strains, we determined the complete nucleotide sequence of the novel PIV-3 (GPv)
      genome. A comparison of the nucleotide sequence among PIV-3s, including bovine
      PIV-3, revealed that GPv is closely related to human PIV-3. The results of the
      phylogenetic analysis clearly showed that GPv is a lineage of human PIV-3,
      suggesting that GPv has probably been introduced into guinea pig colonies via
      infected humans.

PMID- 9764405
TI  - Analysis of tumor suppressor gene p53 in chicken lymphoblastoid tumor cell lines
      and field tumors.
AB  - To determine whether there is any abnormalities of the p53 gene in chicken
      lymphoblastoid tumor cell lines derived from Marek's disease (MD), lymphoid
      leukosis, reticuloendotheliosis, and field tumors, some portions of p53 cDNA
      corresponding to core and C-terminal domains (nucleotide positions 277-1104 in
      the p53 open reading frame (ORF)) were sequenced. Several mutations were
      identified in both cell lines and field tumors. However, none of these mutations
      is localized at the "hot spot", which has been reported as the site for
      transformation-activating mutations. Moreover, partial cDNA clones with a 122-bp
      deletion in the p53 ORF were identified in two cell lines, MSB1 and MTB1 derived
      from MD tumors. Southern blot analysis showed that no deletion occurred in the
      genome of p53 in MSB1, indicating that deletion occurred at the transcriptional
      level. This deletion could cause a frame shift of the encoding p53 protein,
      possibly resulting in the generation of a functionally different p53 protein.
      However, we confirmed that p53 mRNA without deletion is also present in each of
      these cell lines. These mutations of the p53 gene and deletion in the p53
      transcript may be ones of molecular changes specific to the transformation
      induced by MD virus.

PMID- 9764406
TI  - Establishment and characterization of a new cell line derived from feline mammary
      tumor.
AB  - A new cell line designated FRM was established from pleural effusion of a 13-year
      old female cat with mammary adenocarcinoma. The cell line exhibited irregular
      round and polygonal shaped epithelial cells and demonstrated cell growth in a
      monolayer fashion with a doubling time of 22.4 hr. It possessed a modal
      chromosome number of 79. The immortality of this cell line was demonstrated using
      the TRAP assay which revealed a high telomeric activity of these cells. Scatchard
      analysis revealed quite low levels of estrogen receptors in both tumor mass
      produced in nude mice and FRM cells. Subcutaneous transplantation of the cells
      produced localized palpable masses in athymic nude mice within two weeks. This
      cell line may provide a good model for in vivo and in vitro studies on feline
      mammary tumors.

PMID- 9764407
TI  - Expression of inhibin alpha-subunit in horse testis.
AB  - Inhibin is believed to play roles in the pituitary secretion of FSH and in the
      paracrine regulation of testicular function. Although it has been generally
      accepted that inhibin is produced in Sertoli cells, there was a recent evidence
      for the localization of inhibin in Leydig cells of primates, rat and sheep.
      However, there is no report on the expression of inhibin in the adult horse
      testis. Therefore, using immunohistochemistry, western blotting and in situ
      hybridization techniques, the present study examined inhibin alpha-subunit (Ih
      alpha) expression in the adult horse testis. For the detection of Ih-alpha
      protein, we used anti-porcine Ih-alpha antibody in immunohistochemistry and
      western blotting. Furthermore, digoxigenin-labeled complementary RNA probes were
      prepared to detect intracellular messenger RNA (mRNA) of Ih-alpha.
      Immunostainings for Ih-alpha were found not only in Leydig cells but also in
      Sertoli cells. The intensity in Leydig cells was stronger than in Sertoli cells.
      Immunoreactivities for Ih-alpha were found at approximately 46 kDa, 56 kDa and 90
      kDa in the homogenates from testicular interstitial tissues. The bands at 56 kDa
      and 90 kDa agree with previous report, but not at 46 kDa. Signals for mRNA of Ih
      alpha by in situ hybridization were detected in Leydig cells and in the basal
      region of seminiferous epithelium including Sertoli cells. These results suggest
      that Ih-alpha is expressed in Leydig cells and Sertoli cells of horse testis, and
      the expression level should be higher in Leydig cells than Sertoli cells.

PMID- 9764408
TI  - Changes in iron and ferritin in anemic calves infected with Theileria sergenti.
AB  - Changes in iron and ferritin in calves infected with Theileria sergenti were
      investigated to elucidate iron metabolism in animals with extravascular hemolytic
      anemia. During severe anemia, serum iron was remarkably elevated while the total
      iron-binding capacity remained relatively unchanged or decreased slightly in the
      infected calves, resulting in elevated transferrin saturation. The serum ferritin
      concentration gradually increased with the progress of anemia. The erythrocyte
      ferritin content drastically increased when mean corpuscular volume was elevated.
      The concentration of non-heme iron and ferritin in the liver, spleen, and bone
      marrow of the infected calves was markedly higher than that in the respective
      tissues of the control animals. In particular, the liver of the anemic calves was
      found to contain 23 and 35 times as much non-heme iron and ferritin,
      respectively, as that of the non-anemic healthy cattle. The liver type (L) to
      heart type (H) subunit ratio of liver ferritin was significantly higher in the
      protozoa-infected than in the non-infected cattle. On the other hand, the L/H
      ratio of marrow ferritin was significantly reduced by the anemia. These results
      indicate that the anemic calves infected with T. sergenti apparently present
      symptoms of iron overload.

PMID- 9764409
TI  - Histopathological study of experimental acute poisoning of cattle by autumn
      crocus (Colchicum autumnale L.).
AB  - Crude or dehydrated bulbs of autumn crocus (Colchicum autumnale L.) were fed to
      eleven calves. All the calves developed severe diarrhea and died or euthanized
      within 63 hr. At necropsy, the gastro-intestinal mucosa was edematous and
      hemorrhagic. Histologically, necrosis and degeneration with karyopyknosis and
      karyorrhexis were shown in the basal cell layer of the tongue, esophagus,
      forestomach, renal pelvis, urinary bladder, neck cell layer of the abomasal
      gastric glands, and intestinal cryps. These findings were also seen in Kupffer
      cells, renal tubular epithelial cells, and lymphocytes in the lymphoid and
      hemopoietic systems. The lesion of the present acute crocus poisoning of cattle
      closely resembled those reported in humans with colchicine intoxication. Refined
      acetone extract of organs of poisoned cattle proved to contain colchicine and
      demecolcine by high performance liquid chromatography.

PMID- 9764410
TI  - Characteristics of lectin staining patterns assessed by a modified sensitive
      thermo-method in rat livers with heterologous serum-induced fibrosis.
AB  - Lectins are sensitive probes which bind carbohydrate structures specifically. In
      this study, we modified the lectin staining procedure for sensitive detection of
      carbohydrate structures in formalin-fixed, paraffin-embedded sections of normal
      and heterologous serum-induced fibrotic livers. The liver sections were heated in
      hot distilled water at 100 degrees C for 10 min (thermo-treatment: TT), and then
      stained with 24 different lectins. In comparison with the results from sections
      without TT (nonTT), enhanced and/or alternated staining patterns of 19 lectins
      were demonstrated in sections with TT, and enhanced staining of Vicia villosa
      agglutinin seen in Kupffer cells was noted. Interestingly, no positive staining
      was seen with Dolichos biflorus agglutinin, peanut agglutinin or soybean
      agglutinin (SBA), which recognize O-linked carbohydrate chains, in Kupffer cells
      of non-TT sections, but strong positive staining was demonstrated in those of TT
      sections. SBA-positive staining in the cytoplasm of some scattered hepatocytes
      located in the periportal and perifibrous zones and central zone of pseudolobules
      was demonstrated only in the fibrotic liver sections with TT. Such findings
      indicate the heterogeneity of hepatocytes in the liver with fibrosis. Formalin
      fixation causes masking of lectin binding sites, especially O-linked carbohydrate
      chains, and TT may recover such masking reactions. TT improved the staining
      reactions for many lectins in formalin-fixed, paraffin-embedded liver sections,
      and new staining patterns appear after TT. Modified TT staining procedures may be
      useful for the diagnosis and prognosis of liver fibrosis.

PMID- 9764411
TI  - Superovulatory responses in Japanese black beef cows following largest follicle
      aspiration or human chorionic gonadotrophin (hCG) treatment.
AB  - The effect of largest follicle aspiration or hCG administration before induction
      of superovulation on the ovarian response of Japanese Black beef cows was
      investigated using a crossover design in which induction of superovulation was
      attempted in every cow. The superovulatory response of cows whose largest
      follicle had been aspirated from the ovaries by ultrasound-guided follicular
      aspiration 1 day before induction of superovulation, did not differ from the
      response in non-treated control cows. In contrast, in cows given 5,000 IU of hCG
      3 days before induction of superovulation, the proportions of fertilized ova and
      transferable embryos significantly decreased compared with the other groups.

PMID- 9764412
TI  - Electroejaculation and semen characteristics of the captive Hokkaido brown bear
      (Ursus arctos yesoensis).
AB  - An electroejaculation technique was applied to the Hokkaido brown bear (Ursus
      arctos yesoensis) for semen collection and characterization of their seminal
      traits. Ten captive sexually mature bears were anesthetized and subjected to 21
      electroejaculation trials during their mating season in 1995 and 1996. Spermic
      electroejaculates were recovered from 6 of the 10 bears (14 of 21 trials). The
      semen was characterized by serous fluid of semitransparent white color and a
      neutral pH. The mean values of ejaculate volume, sperm concentration, percentage
      of sperm motility, percentage of live spermatozoa, and percentage of pleiomorphic
      forms were 2.7 ml, 471.6 x 10(6) cells/ml, 80.2%, 89.7% and 21.8%, respectively.
      Although there was considerable variation among the seminal traits of the
      individual bears, the electroejaculation technique was effective in obtaining
      ejaculates from captive bears.

PMID- 9764413
TI  - Higher sensitivity in LEC rat cells to a topoisomerase II inhibitor, ellipticine.
AB  - A concentration of ellipticine, an inhibitor of topoisomerase II, required to
      reduce cell survival to 37% (D37) is used as an index to compare the cellular
      sensitivity. D37 values of LEC and WKAH rat cells were 1.2 and 2.2 microM,
      respectively. Thus, LEC rat cells were approximately 1.8-fold more sensitive than
      WKAH rat cells to ellipticine. There was no significant difference between the
      topoisomerase II activities in nuclear extracts of LEC and WKAH rat cells. These
      results suggested that the high sensitivity of LEC rat cells to ellipticine is
      not associated with the level of topoisomerase II activity.

PMID- 9764414
TI  - New quantitative methods for detection of feline parvovirus (FPV) and virus
      neutralizing antibody against FPV using a feline T lymphoid cell line.
AB  - Previously, we reported that a feline T lymphoid cell line, FL74 cells, was very
      sensitive to feline parvovirus (FPV) infection. In the present study, we
      developed new quantitative methods for detection of FPV and virus neutralizing
      antibody against FPV using FL74 cells. The methods presented here were very
      simple and applicable to both canine parvovirus and feline panleukopenia virus.

PMID- 9764415
TI  - Canine mesenchymal chondrosarcoma of the ribs.
AB  - The tumor of the thoracic cavity, which arose from the ribs, was diagnosed as
      mesenchymal chondrosarcoma. No distant metastasis was observed. Histologically,
      the tumor was characterized by the nests of well-defined cartilaginous tissue
      within a proliferation of primitive mesenchymal cells. Additionally, the deformed
      blood vessels compressed by the proliferating mesenchymal cells exhibited clear
      stag-horn appearance. Immunohistochemically, most neoplastic cells that formed
      multifocal cartilaginous islands were positive for S-100 protein, while the
      surrounding mesenchymal cells were negative. This is the first report of canine
      mesenchymal chondrosarcoma of the ribs.

PMID- 9764416
TI  - Gastric mucormycosis in a sika deer (Cervus nippon) associated with proliferation
      of Clostridium perfringens.
AB  - Seven sika deer (Cervus nippon) died in a park where 30 deer were kept. One adult
      female deer died suddenly was necropsied. Severe hemorrhages were noted beneath
      the serous membranes of the forestomach and abomasum. Hyphal proliferation with
      neutrophil infiltration was observed in the mucous membranes of the stomaches,
      and the hyphae showed characteristics of order Mucorales. Catarrhal enteritis
      with hemorrhages was also observed. A large number of Clostridium perfringens was
      isolated from the contents of the abomasum and small intestine. The case was
      diagnosed as gastric mucormycosis associated with proliferation of Clostridium
      perfringens. The incidence occurred during breeding season and incorrect
      management was considered to be a predisposing factor for the infection.

PMID- 9764417
TI  - Presence of 22- and 17-kDa proteins reacting with sera in mice experimentally
      infected with Brachyspira (Serpulina) hyodysenteriae.
AB  - The antibodies to B. (S.)hyodysenteriae in experimentally infected mice were
      detected by microscopic agglutination test (MAT) and enzyme-linked immunosorbent
      assay (ELISA). The reactions in MAT were serotype specific while those in ELISA
      were common to both strains. A further investigation with immunoblotting
      technique demonstrated that 22- and 17-kDa proteins reacted strongly with the
      sera. The proteins in ATCC 27164 strain strongly reacted with the serum from ATCC
      31212 strain-infected mouse and vice versa. These proteins were sensitive to
      proteinase K.

PMID- 9764418
TI  - Enhancement of neonatal rat ductal responsiveness to prostaglandin E2 after
      maternal treatment with enalapril or captopril.
AB  - This work was conducted to determine whether the angiotensin-converting enzyme
      inhibitors (ACEIs) (enalapril and captopril) administered to mother rats
      prenatally can potentiate a re-opening of the neonatal ductus arteriosus (DA)
      induced by prostaglandin E2 (PGE2) after postnatal closure. A subcutaneous
      injection of PGE2 (4 micrograms) was administered to newborn rats 3 hr after a
      Cesarean delivery from females which had been orally given 0.1, 1 or 10 mg/kg/day
      of enalapril or 15 or 150 mg/kg/day of captopril from day 14 to day 20 of
      gestation. The ratio of the DA to the pulmonary artery (PA) was determined at
      intervals after the injection. The DA/PA ratio was significantly higher in the
      newborn rats of mothers who were transplacentally administered these agents
      compared to the controls, except at the low dose (0.1 mg/kg) group of enalapril.
      We found that the level in the neonatal lungs of 15-hydroxy prostaglandin
      dehydrogenase, a key enzyme that catalyzes PGE2 to convert it to its inactive
      metabolite 15-keto-PGE2, was not affected after maternal treatment with enalapril
      or captopril. These results indicate that the increased ductal responsiveness to
      PGE2 in newborn rats was a common response after maternal ACEI treatment, but the
      catabolism of PGE2 in the lungs did not contribute to this response.

PMID- 9764419
TI  - Paraquat: a useful tool for the in vivo study of mechanisms of neuronal cell
      death.
AB  - The present article reviews the results of experimental studies on paraquat
      neurotoxicity, started by our group several years ago--when clinical and
      experimental reports had increased the interest for the possibility that
      environmental chemicals, including paraquat, may be related to the development of
      Parkinson's disease-, and which are still continuing since paraquat appears to be
      a promising tool to study the mechanisms of neuronal cell death in vivo. Our
      observations have demonstrated that paraquat causes evident neurotoxic effects
      after intracerebroventricular or intracerebral injection in experimental animals;
      however, it seems that the herbicide does not exibit a selective neurotoxicity
      towards the dopaminergic nigro-striatal system since potent behavioural and
      electrocortical changes are induced by paraquat after injection in brain areas
      other than the substantia nigra and caudate nucleus. By studying the mechanisms
      through which paraquat induces neurotoxic effects in vivo, it was shown that
      either free radical production and activation of cholinergic and glutamatergic
      transmission may be regarded as related events which play a crucial role in
      paraquat-induced neurotoxicity. In addition, it was observed that in rats
      paraquat penetrates the blood-brain barrier following systemic administration to
      give rise to a differential brain regional distribution; the latter observation
      rises some concern over the hazard of paraquat as a potential environmental
      neurotoxin. Indeed, paraquat, administered systemically in rats produces
      behavioural excitation and brain damage. The brain damage appears to be selective
      for the pyriform cortex and this does not seem to be strictly related to the high
      concentrations reached by the herbicide in this area but to the higher
      vulnerability of this cortical area to the enhanced cholinergic transmission. The
      recent observation that paraquat, injected into the rat hippocampus, induces the
      expression of apoptotic neuronal cell death, appears of valuable interest also
      with a view to paraquat as an useful experimental model in the development of
      neuroprotective drugs able to block the molecular events which, once activated,
      are responsible for the induction of neuronal cell death.

PMID- 9764420
TI  - Gadolinium chloride inhibition of pulmonary nitric oxide production and effects
      on pulmonary circulation in the rabbit.
AB  - Nitric oxide is an important regulator of pulmonary vascular resistance.
      Pulmonary nitric oxide formation is detectable in exhaled air and the synthesis
      is partly stretch-dependent. Gadolinium chloride (GdCl3) reduces pulmonary nitric
      oxide formation, possibly by interference with stretch-activated cellular calcium
      influx, but the effect on pulmonary circulation is not known. We therefore
      measured exhaled nitric oxide and pulmonary vascular resistance in anaesthetised
      rabbits, and compared the effects of GdCl3 with those of an nitric oxide-synthase
      inhibitor (L-N omega-nitro-arginine methyl ester, L-NAME). Both GdCl3 and L-NAME
      reduced nitric oxide in exhaled air and increased pulmonary vascular resistance.
      However, the increase in pulmonary vascular resistance was more pronounced with
      GdCl3 than with L-NAME. A 50% reduction of exhaled nitric oxide caused by either
      GdCl3 or L-NAME was accompanied by a 90% or 17% increase in pulmonary vascular
      resistance respectively. Inhaled nitric oxide (40 ppm) reduced pulmonary vascular
      resistance after L-NAME, but not after GdCl3 infusion. Infusion of
      glyceryltrinitrate reduced pulmonary vascular resistance after GdCl3 infusion.
      GdCl3 caused hypoxaemia, probably due to vasoconstriction since lung weight was
      unaltered. Thus GdCl3 can induce a marked increase in pulmonary vascular
      resistance, which partly may be caused by inhibition of pulmonary nitric oxide
      formation. Intact stretch-activated calcium channels may be important for
      maintenance of normal pulmonary vascular function.

PMID- 9764421
TI  - Effects of ATP-sensitive potassium channel opener on potassium transport and
      alveolar fluid clearance in the resected human lung.
AB  - Since the effect of an ATP-sensitive potassium channel (KATP channel) opener on
      the function of alveolar epithelial cells is unknown, the effect of YM934, a
      newly synthesized KATP channel opener, on potassium influx into the alveolar
      spaces and alveolar fluid clearance was determined in the resected human lung. An
      isosmolar albumin solution with a low potassium concentration was instilled into
      the distal airspaces of resected human lungs. Alveolar fluid clearance was
      measured by the progressive increase in alveolar protein concentration. Net
      potassium transport was measured by the change in potassium concentration and
      alveolar fluid volume. YM934 (10(-4) M) increased net influx of potassium by 140%
      into the alveolar spaces and also increased alveolar fluid clearance by 60% in
      the experiments with a potassium concentration of 0.3 mEq/1. Glibenclamide (10(
      4) M), a KATP channel blocker, inhibited the YM934-increased influx of potassium
      transport and the increase in alveolar fluid clearance. Also amiloride (10(-5)
      M), an inhibitors of apical sodium uptake, blocked the YM934 stimulated increase
      in net alveolar fluid clearance. These results indicate that a KATP channel
      opener can effect potassium transport and net vectorial fluid movement across the
      human alveolar epithelium.

PMID- 9764422
TI  - Effect of concomitant beta-adrenoceptor stimulation on alpha 1-adrenoceptor
      mediated increase of inositol-1,4,5-trisphosphate mass in adult rat
      cardiomyocytes.
AB  - The aim of the present study was to investigate the accumulation of inositol
      1,4,5-trisphosphate (IP3) in isolated adult rat ventricular cardiomyocytes after
      alpha 1- and beta-adrenoceptor stimulation, separate and in combination, in order
      to elucidate a possible influence of concomitant beta-adrenoceptor stimulation on
      the alpha 1-adrenoceptor stimulated response. IP3 was measured by a radioligand
      binding assay based on an (1,4,5)IP3-specific binding protein from bovine adrenal
      cortex. The basal IP3 content was 4.06 +/- 0.31 pmol/mg protein (N = 56). alpha 1
      Adrenoceptor stimulation resulted in a rapid increase in the IP3 level, which
      reached a plateau, 50-80% above basal level, at 10-30 sec. The plateau lasted at
      least up to 120 sec., while at 300 sec. there was no significant difference
      between control values and values after alpha 1-adrenoceptor stimulation. Li+ did
      not affect either the basal IP3 level, or the magnitude or time course of alpha 1
      adrenoceptor-stimulated IP3 accumulation. Combined adrenoceptor stimulation gave
      a similar response as separate alpha 1-adrenoceptor stimulation, whereas there
      was no significant change in the IP3 level after beta-adrenoceptor stimulation.
      No inhibitory influence of simultaneous beta-adrenoceptor stimulation on the
      alpha 1-adrenoceptor-stimulated increase of IP3 mass was revealed.

PMID- 9764423
TI  - Growth modulating effects of chlorinated oleic acid in cell cultures.
AB  - Chlorinated fatty acids represent a major fraction of extractable, organically
      bound chlorine in fish. After dietary intake such fatty acids may be transferred
      from the mother to the foetus through the placenta, and via breast milk to the
      child. In the present work we have studied the effect of chlorinated oleic acid
      on the growth of three widely differing types of cells in culture. Chlorinated
      oleic acid inhibited growth of Human Microvascular Endothelial Cells (HMVEC),
      Immortilized Human Kidney Epithelial (IHKE) cells, and human Hepatoma cells
      (HepG2). The order of potency was: HMVEC > IHKE > HepG2. Vitamin E counteracted
      the inhibitory effect of chlorinated oleic acid on HepG2 cells, but did not
      significantly affect the fatty acid effect on HMVEC or IHKE. Defatted serum
      albumin stimulated the growth of HMVEC and IHKE. With HMVEC there was no major
      interaction between the effect of albumin and chlorinated oleic acid on cell
      growth. In contrast, with IHKE albumin at low concentration abolished the growth
      inhibiting effect of chlorinated oleic acid and appreciably counteracted growth
      inhibition by the fatty acid of HepG2. We conclude that the growth modulation by
      chlorinated oleic acid and its interaction with vitamin E and albumin are cell
      specific.

PMID- 9764424
TI  - Methamphetamine-induced modification of dopamine metabolism in cultured striatal
      astrocytes.
AB  - The role of striatal astrocytes in the metabolic processing (by deamination) of
      methamphetamine-released dopamine is not known. To investigate the relationship
      between methamphetamine and dopamine metabolism, we measured 6-hydroxydopamine,
      dopamine and, 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations following
      methamphetamine treatment of cultured striatal astrocytes prepared from 1-2 day
      old rats. Addition of low concentrations of dopamine (5 x 10(-5) to 5 x 10(-4) M)
      to cultured astrocytes increased DOPAC levels in a dose-dependent fashion while
      higher concentrations (5 x 10(-3) to 10(-2) M) inhibited its metabolism and
      induced formation of 6-hydroxydopamine. Under the same experimental conditions,
      10(-4) M dopamine in combination with methamphetamine (10(-5) to 10(-3) M)
      inhibited DOPAC formation and increased dopamine levels in a dose-dependent
      fashion, but the formation of intracellular 6-hydroxydopamine was not evident.
      Deprenyl (10(-5) or 10(-4) M), an inhibitor of monoamine oxidase B, and pargyline
      (10(-5) or 10(-4) M), a non-selective monoamine oxidase inhibitor, completely
      inhibited DOPAC formation and increased dopamine levels, while clorgyline (10(-5)
      or 10(-4) M), an inhibitor of monoamine oxidase-A, only partially inhibited DOPAC
      formation (42 or 45% of control, respectively). These results support the
      hypothesis that methamphetamine inhibits monoamine oxidase and causes increases
      in dopamine levels in cultured striatal astrocytes.

PMID- 9764425
TI  - Characterization of t-butyl hydroperoxide toxicity in cultured rat cortical
      neurones and astrocytes.
AB  - The present study investigates the toxicity of t-butyl hydroperoxide (t-BuOOH) in
      cultured rat cortical neurones and astrocytes. Both neurones and astrocytes were
      destroyed by exposure to t-BuOOH in a time- and concentration-dependent manner.
      Astrocytes were more resistant to destruction by hydrogen peroxide (H2O2) than
      neurones, but there was no difference in susceptibility to t-BuOOH between
      neurones and astrocytes. The toxic effect of t-BuOOH was significantly blocked by
      antioxidants, propyl gallate and trolox, but not by superoxide dismutase nor by
      H2O2-scavengers, catalase and 4-nitrophenylglyoxylic acid. These results suggest
      that t-BuOOH toxicity is caused by oxidative stress unrelated to superoxide and
      H2O2. In addition, the toxic effect of t-BuOOH was attenuated by the presence of
      iron chelators, deferoxamine and N,N,N',N'-tetrakis(2
      pyridylmethyl)ethylenediamine, indicating the requirement of endogenous iron for
      t-BuOOH toxicity.

PMID- 9764426
TI  - Advantages and pitfalls of macrostatistics for health planning at the local as
      well as top national level.

PMID- 9764427
TI  - Late postoperative respiratory function in adults after surgical correction of
      atrial septal defects. Analysis of respiratory dysfunction patterns.
AB  - Respiratory function after repair of atrial septal defect (ASD) was analysed in
      44 adults (> 40 years), 21 of whom had preoperative respiratory dysfunction, 14
      of restrictive type, defined as % vital capacity (% VC) less than 80% of
      predicted value, 3 with an obstructive pattern, defined as % forced expiratory
      volume/1 s (% FEV1) less than 70% of predicted value, and 4 patients with a mixed
      pattern. Increased % VC was found postoperatively in all 14 patients with
      restrictive respiratory dysfunction, with normal values in 8 out of the 14.
      Although the three patients with obstructive, and the four with mixed-pattern
      respiratory dysfunction improved preoperatively in % VC or % FEV1, or both, none
      had normalized values. We conclude that preoperative restrictive respiratory
      dysfunction in ASD patients frequently normalizes postoperatively, but not
      dysfunction of obstructive or mixed restrictive-obstructive type.

PMID- 9764428
TI  - Effects of a novel pneumatic vest on postoperative pain and lung function after
      coronary artery bypass grafting.
AB  - A prospective study to evaluate the efficacy of a novel inflatable vest in
      supporting the sternotomy wound during the early period after coronary artery
      bypass grafting was carried out in 35 patients. The outcome variables were
      subjective pain score during cough, and peak expiratory flow (PEF) and vital
      capacity (VC) on postoperative days 2 and 3. The values without pressure in the
      vest were used as controls in the individual patients. Use of the vest
      significantly reduced the cough-associated subjective sternotomy pain score on
      days 2 and 3, when significant reduction of PEF and VC was also observed. The
      alleviation of pain by the inflatable vest may improve the efficacy of coughing
      and bronchial clearance in the immediate postoperative period.

PMID- 9764429
TI  - Assessment of myocardial glutamate requirements early after coronary artery
      bypass surgery.
AB  - Glutamate is an important substrate for the intermediary metabolism of the heart,
      particularly in association with ischemia. Early after coronary artery bypass
      surgery (CABG) myocardial uptake of glutamate seems to be limited by substrate
      availability (arterial levels). However, glutamate is not an innocuous substrate.
      As arterial levels of glutamate are important both for myocardial uptake and
      adverse effects, an attempt was made to determine a minimum dose of glutamate
      sufficient to supply the needs of the heart after CABG. Ten patients received and
      infusion of 220-240 ml of 0.1 M L-glutamic acid solution at varying rates during
      two 30-min periods, starting 2 h after uncomplicated elective CABG. Intravenous
      glutamate infusion caused a dose-dependent linear increase in arterial glutamate
      and an increased myocardial uptake of glutamate. However, myocardial uptake of
      glutamate correlated with arterial levels only at lower infusion rates. Although
      maximal peak uptake in individual patients (6.6 +/- 1.1 mumol/min) occurred at an
      average increase of arterial whole blood glutamate of 172 +/- 34 mumol/L, the
      greatest impact on myocardial glutamate uptake was achieved by increasing
      arterial whole blood glutamate by less than 100 mumol/L. This implies that an
      infusion rate of 30-40 mg glutamate/kg BW/h could suffice to achieve a maximal or
      near maximal myocardial glutamate uptake in most patients after CABG. The
      adequacy of this dosage remains to be confirmed in high-risk patients.

PMID- 9764430
TI  - Benign intrathoracic tumours. A population survey in northern Finland.
AB  - Benign intrathoracic tumours are uncommon, but their occurrence in unselected
      populations is poorly defined. We reviewed all cases of suspected intrathoracic
      tumour in a population (440,000) in northern Finland during 1990 through 1992.
      Diagnostic investigations included fiberoptic bronchoscopy and computed
      tomography in all cases. Of the 653 intrathoracic tumours, 36 were benign. The
      male/female ratio in these 36 cases was 1.25; the mean age was 54 years. Twenty
      three of the lesions were symptomless, found at health check or examination for
      other disease. Bronchoscopy did not confirm the diagnosis of any benign tumour.
      Thoracotomy was considered necessary in most cases and histologic diagnosis was
      therefore available in 24 (67%). Hamartoma was the most common benign lung
      tumour. This prospective study in an unselected population confirms previous
      findings in surgical series concerning benign intrathoracic tumours and their
      histology.

PMID- 9764431
TI  - Differences in heart rate variability in the acute phase of first and second
      attacks of myocardial infarction.
AB  - The purpose of the study was to examine the differences between first and second
      myocardial infarctions with respect to improvement in measures of heart rate
      variability (HRV). The study population comprised 48 non-diabetic patients with
      acute myocardial infarction (AMI), and with angiographically documented coronary
      artery occlusion and successful reperfusion. The subjects were grouped as 35
      cases with a first AMI attack and 13 with their second AMI. Two weeks after the
      onset of infarction, indices of HRV were higher in first infarction cases than in
      second infarction cases. In the latter, there were no significant increases in
      HRV indices from day of onset to 2 weeks later, nor were there any significant
      changes in left ventricular ejection fraction (LVEF) from onset to 3 weeks later.
      All patients studied had a patent infarct-related artery 3 weeks later. We found
      sustained low values of HRV after a second AMI. Different risk stratification may
      be needed between uncomplicated first AMI and second AMI cases.

PMID- 9764432
TI  - Urinary albumin excretion in hospitalized patients with acute myocardial
      infarction. Prevalence of microalbuminuria and correlation to left ventricle wall
      thickness.
AB  - Microalbuminuria, a subclinical rise in the urinary albumin excretion, is a risk
      indicator of atherosclerotic cardiovascular disease. The aim of this study was to
      measure the urinary albumin excretion in patients with acute myocardial
      infarction, and to correlate this with known atherosclerotic risk factors. One
      hundred-and-twenty-six patients and 56 healthy controls matched for age and sex
      were studied. The albumin/creatinine concentration ratio in morning urine
      specimens was calculated as an index of the albumin excretion. Microalbuminuria
      was defined as a urinary albumin/creatinine concentration ratio above 1 mg/mmol.
      Urinary albumin excretion (0.88 [95% confidence interval 0.69-1.11] versus 0.51
      [0.40-0.63] mg/mmol; p = 0.001) and frequency of microalbuminuria (33 [95%
      confidence interval 25-41] versus 16 [9-23]%; p = 0.03) were higher in patients
      than controls. This difference was independent of blood pressure, body weight,
      smoking, diabetes mellitus, renal disease, and thrombolytic treatment. There was
      a positive correlation between urinary albumin excretion and thickness of the
      left ventricle wall (R = 0.28; p = 0.001) which was independent of blood
      pressure. Follow-up examination of the patients will reveal whether
      microalbuminuria increases the risk for recurrence of acute myocardial
      infarction.

PMID- 9764433
TI  - Effect of amiloride on ischaemia and reperfusion injury in isolated, perfused rat
      hearts.
AB  - The effect of amiloride, a potent inhibitor of Na+/H+ exchange, on ischaemic
      reperfused rat hearts was studied in order to investigate whether Na+/H+ exchange
      or Na+/Ca2+ exchange is involved in ischaemia-reperfusion injury, When hearts
      were pre-ischaemically loaded with 100 microM amiloride, recovery of left
      ventricular developed pressure was significantly better than in control hearts,
      whereas recovery of heart rate at 30-min reperfusion was unaffected. Amiloride
      pretreatment also decreased creatine phosphokinase activity in the coronary
      effluent and completely abolished occurrence of ventricular arrhythmias during
      reperfusion. It also inhibited intracellular Na+ accumulation early in
      reperfusion (within 5 min), whereas in the late stage (from 5 to 30 min), Ca2+
      overload was inhibited. The findings suggest that Na+/H+ exchange participates
      mainly in the early stage of reperfusion injury and the Na+/Ca2+ exchange system,
      secondary to Na+/H+ exchange, in the late stage. The reduction in post-ischaemic
      cardiac dysfunction induced by amiloride pretreatment may be attributable to
      inhibition of the resultant Ca2+ accumulation during reperfusion.

PMID- 9764434
TI  - Malignant transformation of an intrathoracic neurofibroma in von Recklinghausen's
      disease.
AB  - Malignant transformation of a mediastinal neurofibroma, presenting for many years
      as a mass in the superior mediastinum and arising from the right vagus nerve, was
      found in a patient with long-standing von Recklinghausen's disease. Surgical
      management of intrathoracic neurogenic tumours, even if clinically benign, is
      advocated.

PMID- 9764435
TI  - Chondrosarcoma of the chest wall with Ollier's disease.
AB  - A 15 x 15 cm mass in the right hemithorax of a 25-year-old woman was incidentally
      detected at routine chest radiography. Radical excision of the bony chest wall,
      including right CII-VI, revealed chondrosarcoma. Large, expansile parosteal
      chondromas were radiographically visualized in the pelvis and bones of the lower
      leg, representing Ollier's disease. Chondrosarcoma of the chest wall appears to
      be rare in Ollier's disease.

PMID- 9764436
TI  - Salmonella osteomyelitis of the rib.
AB  - Salmonella rib osteomyelitis is extremely rare; we found only one previously
      reported case. A 33-year-old man presenting with a discharging sternal sinus was
      diagnosed by means of computed tomography and bone isotope scans and confirmed by
      excision of the affected portion of the rib. The operation was curative.

PMID- 9764437
TI  - Quantity and quality relationships in cardiovascular medicine.
AB  - Hospital volume and often also operator volume have documented impacts on the
      quality of care for aortic and aortocoronary bypass surgery, for percutaneous
      angioplasty and for radiofrequency ablation for arrhythmias, whereas data are
      less consistent for treatment of acute myocardial infarction. A review of this
      research is given. In the Nordic countries hospitals are small, and often the
      plateau of the learning curve cannot be reached. To discourage low-volume centers
      from embarking upon too complicated interventional or surgical procedures, the
      author suggests that a minimal number should be set for certain major procedures,
      both for hospitals and for physicians.

PMID- 9764438
TI  - Release and effects of calcitonin gene-related peptide in myocardial ischaemia.
AB  - 1. Low pH and lactic acid perfusion evoke a reproducible, and concentration
      dependent outflow of CGRP from the isolated heart. 2. PGI2 causes outflow of CGRP
      from the isolated heart. Furthermore, low pH perfusion causes release of PGI2,
      and cyclo-oxygenase inhibition attenuates not only this release of PGI2, but also
      the outflow of CGRP that is evoked by low pH perfusion, indicating that a portion
      of the C-fibre activation exerted by low pH is mediated by PGI2. 3. The outflow
      of CGRP that is caused by low pH but not that evoked by capsaicin or PGI2 is
      dependent on the endothelium, whereas the vasodilating effect of CGRP is
      preserved after removal of the endothelium. 4. TTX attenuates release of CGRP
      caused by low concentrations of capsaicin, indicating that an axon reflex
      mechanism in the peripheral endings of C-fibre afferents can augment local
      outflow of CGRP. 5. Outflow of CGRP evoked by low pH and capsaicin have common
      features, such as sensitivity to RR and CPZ. N-type calcium channels are involved
      in release of CGRP by both stimuli. 6. In the coronary vasculature, exogenous
      CGRP augmented post-occlusive hyperaemia. 7. In the pig in vivo, CGRP causes
      marked dose-dependent reduction of systemic vascular resistance. This effect of
      CGRP was partly reduced by CGRP(8-37). 8. Capsaicin pretreatment resulted in
      lower myocardial levels of CGRP, and ischaemic myocardium had lower content of
      CGRP than non-ischaemic areas. Capsaicin-treated animals had larger myocardial
      infarctions, possibly due to depletion of CGRP. When endogenous stores of CGRP
      were intact, administration of additional CGRP to the ischaemic myocardium had no
      cardioprotective effect. 9. In patients undergoing CABG without CPB, 10-20
      minutes of local ischaemia (as evidenced by a net production of lactate) was
      associated with increased levels of CGRP in coronary sinus blood. 10. Based on
      the present findings it may therefore be suggested that local cardiac CGRP
      release from capsaicin-sensitive C-fibre afferents during myocardial ischaemia
      functions as an endogenous physiological protective response. The possibility
      thus exists that effects of CGRP observed in animal studies may play a role in
      human myocardial ischaemia.

PMID- 9764439
TI  - Subtalar instability of the foot. A review and results after surgical treatment.
AB  - Most subtalar ligamentous injuries occur in combination with ankle ligament
      injuries, but the exact aetiology and the true incidence remain unknown. The aim
      of this study was to review the problem, propose a definition and to analyze the
      results of an anatomic reconstructive surgical technique in the treatment of
      subtalar instability. Twenty-two patients suffering from chronic subtalar
      instability of the foot were operated with anatomical reconstruction. The
      cervical, the lateral talo-calcaneal and the calcaneo-fibular ligaments were
      imbricated and reinforced with the lateral root of the inferior extensor
      retinaculum. After a minimum of 2 years follow-up the functional results were
      excellent or good in 18 of 22 (82%) patients and fair or poor in 4 of 22 (18%).
      All of the patients with unsatisfactory results suffered from residual ankle
      pain, two of whom also had residual instability. No reoperations have been
      performed. Surgical complications were seen in three patients, all minor nerve
      injuries of the lateral branch of the superficial peroneal nerve. These
      complications had no bearing on the functional results, however. This procedure
      was found to be feasible in patients with chronic subtalar instability.

PMID- 9764440
TI  - Stabilometry and one-leg hop test have high test-retest reliability.
AB  - The purpose of this study was to investigate the reliability of repeated
      measurements and a possible learning or tiring process in single-limb
      stabilometry and one-leg hop test. An additional purpose was to study the
      correlation between different stabilometric variables. Seventy-five healthy
      subjects were examined twice with a median interval of 7 d, and with three
      consecutive measurements on each occasion. Single-limb stabilometry and one-leg
      hop test were found to have high reliability (ICC r = 0.68-0.83 and 0.96,
      respectively). The correlation between consecutive measurements was acceptable to
      high in stabilometry (r = 0.42-0.90, P = 0.002-P < 0.001) and high in the one-leg
      hop test (r = 0.91-0.97, P < 0.001). A learning process over time was observed.
      The correlation between the stabilometric variables was high (r = 0.73-0.95, P <
      0.001).

PMID- 9764441
TI  - Aerobic endurance testing of children and adolescents--a comparison of two
      treadmill-protocols.
AB  - Fifty-eight children and adolescents of both sexes, aged 8-16, were tested on a
      treadmill using two different protocols. The well-known Bruce-protocol has the
      disadvantages of steep incline and large increments at each step. A new protocol
      (Oslo-protocol) with less incline and smaller increments was compared to the
      Bruce-protocol. The results from the two protocols showed no differences with
      regard to peak oxygen uptake (VO2peak) or peak heart rate (HRpeak). However, the
      respiratory exchange ratio (R) and blood lactate concentration [La-] showed
      higher values when the Bruce-protocol was used. The study also indicated that the
      often used criteria of HRpeak, R and achievement of a plateau in VO2 to estimate
      VO2peak, were not reliable indicators in either protocol. When time to exhaustion
      was used as an estimation of aerobic endurance level, the Oslo-protocol
      discriminated better than the Bruce-protocol. As a conclusion, the results
      indicate that none of the criteria may be used as a reliable indicator of having
      achieved VO2peak. An experienced testleader may be essential to define when
      VO2peak has been reached in children. On the basis of the results from the
      current study, the Oslo-protocol seems suitable as a test-protocol when testing
      children and adolescents for VO2peak.

PMID- 9764442
TI  - Isokinetic eccentric exercise as a model to induce and reproduce
      pathophysiological alterations related to delayed onset muscle soreness.
AB  - Physiological alterations following unaccustomed eccentric exercise in an
      isokinetic dynamometer of the right m. quadriceps until exhaustion were studied,
      in order to create a model in which the physiological responses to physiotherapy
      could be measured. In experiment I (exp. I), seven selected parameters were
      measured bilaterally in 7 healthy subjects at day 0 as a control value. Then
      after a standardized bout of eccentric exercise the same parameters were measured
      daily for the following 7 d (test values). The measured parameters were: the
      ratio of phosphocreatine to inorganic phosphate (PCr/Pi), the ratio of inorganic
      phosphate to adenosintriphosphate (Pi/ATP), the ratio of phosphocreatine to
      adenosintriphosphate (PCr/ATP) (all three ratios measured with 31P-nuclear
      magnetic resonance spectroscopy), dynamic muscle strength, plasma creatine kinase
      (CK), degree of pain and "muscle" blood flow rate (133Xenon washout technique).
      This was repeated in experiment II (exp. II) 6-12 months later in order to study
      reproducibility. In experiment III (exp. III), the normal fluctuations over 8 d
      of the seven parameters were measured, without intervention with eccentric
      exercise in 6 other subjects. All subjects experienced pain, reaching a maximum
      48 h after eccentric exercise in both exp. I and II. A systematic effect over
      time for CK (increasing 278% resp. 308%), muscle strength (decreasing more than
      10%), PCr/Pi (decreasing 31% resp. 43%) and Pi/ATP (increasing 55% resp. 99%) was
      found in both exp. I and II (P < 0.05), but not in exp. III. No significant
      difference was observed between exp. I and II for CK, blood-flow rate, concentric
      muscle strength, PCr/Pi, Pi/ATP and PCr/ATP. It is concluded that
      pathophysiological alterations in m. quadriceps following eccentric exercise can
      be induced and can be reproduced after an interval of 6 months. Thus, this model
      can be used to study the effects of physiotherapy.

PMID- 9764443
TI  - The effect of passive stretching on delayed onset muscle soreness, and other
      detrimental effects following eccentric exercise.
AB  - The aim of this study was to measure if passive stretching would influence
      delayed onset muscle soreness (DOMS), dynamic muscle strength, plasma creatine
      kinase concentration (CK) and the ratio of phosphocreatine to inorganic phosphate
      (PCr/P(i)) following eccentric exercise. Seven healthy untrained women, 28-46
      years old, performed eccentric exercise with the right m. quadriceps in an
      isokinetic dynamometer (Biodex, angle velocity: 60 degrees.s-1) until exhaustion,
      in two different experiments, with an interval of 13-23 months. In both
      experiments the PCr/P(i) ratio, dynamic muscle strength, CK and muscle pain were
      measured before the eccentric exercise (day 0) and the following 7 d. In the
      second experiment daily passive stretching (3 times of 30 s duration, with a
      pause of 30 s in between) of m. quadriceps was included in the protocol. The
      stretching was performed before and immediately after the eccentric exercise at
      day 0, and before measurements of the dependent variables daily for the following
      7 d. The eccentric exercise alone led to significant decreases in PCr/P(i) ratio
      (P < 0.001) and muscle strength (P < 0.001), and an increase in CK concentration
      (P < 0.01). All subjects reported pain in the right m. quadriceps with a peak 48
      h after exercise. There was no difference in the reported variables between
      experiments one and two. It is concluded that passive stretching did not have any
      significant influence on increased plasma-CK, muscle pain, muscle strength and
      the PCr/P(i) ratio, indicating that passive stretching after eccentric exercise
      cannot prevent secondary pathological alterations.

PMID- 9764444
TI  - The energy cost of level walking before and after hydro-kinesi therapy in
      patients with spastic paresis.
AB  - In this study the energy cost of level walking was measured in 23 patients with
      stationary spastic paresis before and after a two-week treatment (45 min daily)
      of hydro-kinesi therapy, the latter consisting of passive and active movements in
      warm (32 degrees C) sea water, free swimming and water immersion walking. Among
      the subjects (80.2 +/- 13.2 kg body mass; 56.0 +/- 14.6 years of age; 10.7 +/-
      6.6 years of duration of spasticity), 12 were affected by hemiparesis, 4 by
      multiple sclerosis and 7 by spinal cord injury. The energy cost of level walking
      (Cw) was measured before and after therapy from the ratio of the overall steady
      state oxygen consumption to the effective speed of progression. The differences
      in Cw due to the treatment, at matched speeds, were found to be negligible at
      speeds higher than 0.75 m.s-1 (less than 5%) but to increase, with decreasing
      speed, up to about 17% at 0.1 m.s-1. The treatment was therefore effective in
      improving the gait characteristics of the subjects, through a decrease of their
      Cw, mainly at low speeds of progression.

PMID- 9764445
TI  - Coronary heart disease risk factors in middle-aged former top-level athletes.
AB  - A cross-sectional study was conducted to determine the impact of previous
      athleticism on coronary heart disease (CHD) risk factors in 168 middle-aged men
      and 147 middle-aged women in Estonia. Participants were divided into four groups:
      physically active ex-athletes (AA), sedentary ex-athletes (SA), recreational
      exercisers (RE), and non-exercisers (NE). The Sharkey's questionnaire was applied
      to determine the CHD risk factors, health habits, medical, safety, personal,
      psychological and women's risk factors scores. Anthropometric characteristics,
      resting systolic and diastolic blood pressure values (SBP, DBP), and physical
      working capacity (PWC170) were measured. Concentrations of total cholesterol
      (CHOL), high-density lipoprotein cholesterol (HDL-C), triacylglycerols (TG), and
      glucose were determined. Low-density lipoprotein cholesterol (LDL-C) and HDL
      C/CHOL ratio were computed. From the questionnaire results, significant
      differences in CHD risk scores in both sex groups in favour of AA and RE were
      found. DBP in men was significantly higher in SA, and SBP in women was
      significantly higher in NE in comparison with other groups. PWC170 and PWC170/kg
      was highest in AA and lowest in NE in both sex groups. There were no significant
      differences for blood biochemical parameters between women's groups. In men, AA
      had a lower CHOL level in comparison with SA and NE, and lower concentrations of
      TG and LDL-C than other groups. AA and RE had a higher HDL-C concentration and
      HDL-C/CHOL ratio in comparison with the other groups. In conclusion, differences
      in CHD risk factors were related to current physical activity, and were more
      expressed in men than in women.

PMID- 9764446
TI  - Effects of walking training on health-related fitness in healthy middle-aged
      adults--a randomized controlled study.
AB  - The effects of walking training on VO2max, serum lipoproteins and plasma
      fibrinogen were studied in 119 healthy middle-aged persons. Training prescription
      was 65-75% of VO2max, 50 min/session, four times a week for 15 weeks. The net
      difference (between pre-posttraining changes in the walking and control group)
      was statistically significant for VO2max (0.14 l .min-1, 95% CI 0.04, 0.23),
      total cholesterol (-0.20 mmol.l-1, CI -0.34, -0.06), LDL cholesterol (-0.17
      mmol.l-1, CI -0.29, -0.05), ratio of HDL cholesterol to total cholesterol (0.014,
      CI 0.005, 0.023), and triglycerides (-0.15 mmol.l-1, CI -0.26, -0.04). No
      statistically significant changes occurred in fibrinogen. The findings indicate
      that walking training of moderate intensity resulted in a modest increase in
      VO2max and minor but consistently favorable changes in serum lipoproteins.

PMID- 9764447
TI  - Snapping popliteal tendon as a source of lateral knee pain.
AB  - A 25-year-old female patient underwent surgery for a history of pain and popping
      on the lateral aspect of her right knee. It was initially thought that the
      patient had iliotibial (IT) band syndrome which was refractory to conservative
      treatment. However, upon release of the IT band, the snapping which was audible
      and palpable pre-operatively was still present. Further exploration of the
      posterior-lateral aspect of the knee revealed that the popliteal tendon was
      snapping over the incisura poplitea extensoria on the lateral femoral condyle.
      Excision of the prominent portion of the articular ridge below the sulcus
      popliteus eliminated the snapping sensation. The patient has remained
      asymptomatic since surgery for the past 22 months.

PMID- 9764448
TI  - Two unconventional testimonies of urolithiasis in the 18th century on the 1600th
      anniversary of St. Liborius' death (397-1997)
AB  - Urolithiasis can be traced back to periods long past, and its pathological
      substrate was well known from the beginning. This knowledge motivated rational,
      empirical measures of healing, which included a variety of recipes against
      stones. The paper presents two unconventional testimonies of urolithiasis in the
      18th century. The Croatian Glagolitic prayerbook from the 18th century is a
      valuable source for identification of therapeutical approaches. On the other
      hand, a votive painting of Saint Liborius, patron saint against lithiasis,
      reflects theurgical views of disease and healing. On the occasion of the 1600th
      anniversary of his death, this paper aims to illustrate how his cult was
      revitalized in the 18th century.

PMID- 9764449
TI  - A few comments on the recipes against kidney stones in the Croatian prayerbook.

PMID- 9764450
TI  - Immediate effects of extracorporeal shock waves on the male genital system of
      rabbit. Preliminary report.
AB  - Hemospermia was reported to occur following extracorporeal shock wave lithotripsy
      of lower ureteric stones. Because no studies showed clearly the possible effect
      of extracorporeal shock waves (ESW) on the male genital system, we were prompted
      to study this effect. Eighteen male white New Zealand rabbits were divided into
      three groups (six in each) and subjected to different doses of ESW (2000, 3000
      and 4000) using a Dornier MFL 5000. Shocks were focused on the lower parts of the
      bladder. Four animals were used as controls. Two hours later, the animals were
      dissected. Gross examination of the genital systems showed bleeding in the
      testicles and prostates of only some animals, whereas microscopic examination
      revealed bloody spots in the genital structures of all animals. The amount of
      bleeding was ESW dose-independent. In conclusion, ESW showed evident immediate
      effects on the male genital system. Application of shock waves in treating lower
      ureteric or vesical stones in doses between 2000 and 4000 may cause bleeding in
      the structures of this system, which can lead to hemospermia. More studies will
      be needed to show the long-term sequelae of these changes on the male genital
      system.

PMID- 9764451
TI  - Integrality of benign prostatic hyperplasia tissues after transurethral
      thermotherapy evidenced by transmittance fourier transform infrared spectroscopy
      combined with thermal analyzer.
AB  - Transmittance Fourier transform infrared microspectroscopy combined with
      differential scanning calorimetry was used to simulate the clinically
      transurethral thermotherapy of benign prostatic hyperplasia (BPH) by in vitro
      isothermal determination. The simulative study to the thermotherapy of epithelium
      or stroma in BPH tissue was performed at 47 degrees C for 3 h, like clinical
      therapy. Whether thermal treatment can induce changes in the secondary structure
      of epithelium or stroma in BPH tissue was investigated. The results indicate that
      the epithelium and stroma in BPH tissue had different protein secondary
      structures, due to the different compositions of the epithelium and stroma. No
      significant change was evidenced in secondary structure for each sample either
      before or after isothermal study, suggesting the integrality and safety of BPH
      thermotherapy in a 47 degrees C for 3 h treatment course.

PMID- 9764452
TI  - Effects of phytic acid on renal stone formation in rats.
AB  - The effects of phytic acid and phytic acid/zinc mixtures on renal urolith
      development in an animal model of nephrolitiasis were studied. Male rats were
      divided into four groups of 15, 10, 10 and 12 rats each. The rats of Group I were
      treated with ethylene glycol; of Group II with ethylene glycol plus zinc; of
      Group III with ethylene glycol phytic acid; and of Group IV with ethylene glycol
      plus a mixture of phytic acid/zinc. Urine analysis (24 h) was carried out to
      determine the levels of calcium, oxalate, citrate, zinc and phytic acid in each
      group. At the end of the experiment all kidneys were removed and examined
      macroscopically and microscopically for possible crystal/stone locations and the
      total calcium amount in the renal papillary tissue was evaluated. In the rats
      treated with the aqueous phytic acid and phytic acid/zinc mixture, the number of
      calcifications on the papillary tips and the total calcium amount of the
      papillary tissue were significantly reduced compared with the controls treated
      exclusively with ethylene glycol or ethylene glycol plus zinc. Consequently,
      phytic acid and mixtures of phytic acid/zinc may be a useful agent in the
      treatment of patients with calcic urolithiasis.

PMID- 9764453
TI  - A randomized prospective study of transurethral electrovaporization vs laser
      ablation of the prostate in men with benign prostatic hypertrophy.
AB  - OBJECTIVE: A prospective randomized study comparing transurethral
      electrovaporization (TVP) vs laser ablation of the prostate was undertaken to
      compare the efficacy and safety of the procedures. METHODS: A total of 31
      patients underwent treatment, with 20 patients receiving electrovaporization
      surgery and 11 patients undergoing laser treatment. Patients underwent initial
      evaluation consisting of an American Urological Association (AUA) symptom score,
      prostate specific antigen (PSA), uroflowometry, pressure flow, and transrectal
      ultrasound for prostate volume. Patients were seen in follow-up at 1, 3 and 6
      months. RESULTS: A total of 31 patients with a 2:1 randomization of TVP to laser
      treatment were enrolled. The laser patients had a mean pre-operative AUA symptom
      score of 19.0 and scores of 9.0, 6.0 and 5.0 at 1-, 3- and 6-month follow-up. The
      TVP patients had a mean pre-operative symptom score of 22.0 and scores of 7.0,
      8.0 and 5.0 at 1-, 3- and 6-month follow-up. Mean peak uroflow (PF) rate pre
      operative was 10.7 for the laser group and 7.7 for the TVP group. At 1-, 3- and 6
      month follow-up, mean PF rates of 13.3, 17.6 and 16.5 were present for the laser
      patients and 15.0, 17.5 and 14.2 for the TVP group. The differences were not
      statistically significant. There were 6 complications in the laser patients and 7
      complications in the TVP group. Operative time was a mean of 27 min for the laser
      patients and 46 min for the TVP group, and the difference in operative time was
      statistically significant. CONCLUSION: At 6-month follow-up the improvement in
      symptoms score and peak flow rate are comparable in both treatment groups. The
      electrovaporization procedure required significantly longer to perform than the
      laser procedure. Long-term follow-up is required to see if these results remain
      sustainable for electrovaporization therapy.

PMID- 9764454
TI  - Outcome of transurethral prostatectomy in men over 80 years.
AB  - Two-hundred-and-twenty-nine men aged between 80 and 97 years (mean 83 years)
      underwent transurethral prostatectomy (TUR-P) for lower urinary tract symptoms
      (LUTS). All case records were reviewed. The follow-up period was 6-16 years. One
      hundred-and-seven patients underwent operation because of acute urinary
      retention, and 122 because of chronic retention. The mean weight of tissue
      removed was 20 g (1-200 g). The perioperative mortality (< 1 month) was 2% (5
      patients). Postoperative complications occurred in 21% (49 patients). Reoperation
      was performed in 11% (26 cases). The result was considered satisfactory in 196
      patients (86%). The present data demonstrate that transurethral resection of the
      prostate in men over 80 years has a good outcome with an acceptable urological
      complication rate and mortality, and we therefore advocate surgery instead of
      watchful waiting in the fit patient.

PMID- 9764455
TI  - Acute epididymitis and urinary tract anomalies in children.
AB  - OBJECTIVES: To evaluate the incidence of urinary tract infection (UTI) and
      genitourinary malformations in children presenting with acute epididymitis.
      PATIENTS AND METHODS: Twenty-five children between 2 months and 14 years of age
      presenting with acute epididymitis underwent urine culture, abdominal ultrasound,
      voiding cystourethrography and, in selected cases, intravenous pyelography.
      Eleven patients were infants and 14 were older than 1 year. UTIs and
      genitourinary malformations were recorded. Fisher's exact test was used to
      compare the incidence in two age groups. A p value of less than 0.05 was
      considered significant. RESULTS: Seven UTIs and eight genitourinary malformations
      were diagnosed in infants, while in older children three UTIs and three
      malformations were discovered. Infants had a higher rate of associated UTI (p
      0.049) and genitourinary malformations (p 0.017) than did older children.
      CONCLUSIONS: Our data show a close relationship between acute epididymitis in
      infants for both UTIs and genitourinary malformations. Every infant presenting
      with epididymitis would undergo a complete evaluation including abdominal
      ultrasound and voiding cystourethrography. In older children the need for imaging
      should be dictated by clinical history and physical findings.

PMID- 9764456
TI  - Effects of ticlopidine in AV-fistula surgery in uremia. Fistula Study Group.
AB  - Two hundred and fifty-eight patients with uremia who were offered surgery for
      placement of an arteriovenous fistula for hemodialysis were recruited in nine
      regional dialysis centers. The patients were randomized to receive the platelet
      aggregation inhibitory compound ticlopidine, 250 mg b.d., or matching placebo.
      Study medication was targeted at 7, minimum 3, days before scheduled surgery and
      continued for 28 days after surgery. The overall rate of occlusion was 41/260
      evaluable operations (16%), 25/131 (19%) in the placebo group and 16/129 (12%) in
      the ticlopidine group. The risk of early occlusion was a non-significant 35%
      lower in the ticlopidine group. Limited risk factor analysis did not clearly
      identify any subgroup other than females at greater risk of early thrombosis nor
      any subgroup deriving particular benefit from ticlopidine treatment.

PMID- 9764457
TI  - Bacteriuria in a population sample of women: 24-year follow-up study. Results
      from the prospective population-based study of women in Gothenburg, Sweden.
AB  - The aims of the study were to estimate the prevalence of bacteriuria in a female
      urban population, to follow up the same population over the years, and to relate
      bacteriuria to long-term prognosis with respect to mortality and kidney disease.
      The study was based on a randomly selected population sample comprising 1462
      women aged 38-60 years at entrance to the study in 1968-69 with an initial
      participation rate of 90.1%. Bacteriuria was observed in 3-5%, increasing with
      age, and most often asymptomatic. Bacteriuria on one occasion meant increased
      risk of having bacteriuria 6 and 12 years later. The percentages of different
      types of bacteria and the resistance pattern were similar initially and at follow
      up studies after 6 and 12 years. There were no differences in mortality or
      incidence of severe kidney disease during a 24-year follow-up between those with
      and those without bacteriuria in the baseline study.

PMID- 9764458
TI  - Metastasis from renal cell carcinoma to the cervix uteri.
AB  - We report on a patient with clear cell adenocarcinoma of the left kidney and a
      solitary metastasis to the cervix uteri. Metastases from renal cell carcinoma to
      the female genitalia are uncommon and metastatic involvement of the uterus is
      very rare. To our knowledge, no more then five cases have been published. A
      review of the literature is given.

PMID- 9764459
TI  - Vesicouterine fistula twenty years following brachytherapy for cervical cancer.
AB  - This report concerns an extremely rare type of fistula, a vesicouterine fistula,
      in a 59-year-old female occurring twenty years following brachytherapy for
      cervical cancer. The patient presented with a history of recurrent urinary tract
      infections, sensation of incompletely emptying the bladder, nocturia and constant
      leakage of urine for several months. Cystoscopy revealed a fistulous opening and
      an exophytic lesion on the posterior bladder wall. Contrast computerized
      tomography demonstrated a fistulous tract between the posterior bladder wall and
      the anterior aspect of the uterine cavity. She underwent a hysterectomy, excision
      of the bladder fistula and interposition of a vascularized rectus muscle graft.
      Histology of the cervix and bladder only revealed inflammatory changes with no
      evidence of malignancy. The diagnosis and investigation of this extremely rare
      condition are discussed, and the management strategies outlined.

PMID- 9764460
TI  - Traumatic renal artery thrombosis.
AB  - We report the case of a unilateral traumatic thrombosis of the renal artery.
      Revascularization was not performed because the diagnosis was made more than 24 h
      after the injury. Early diagnosis and prompt surgical repair are the keys to
      successful management of this complication.

PMID- 9764461
TI  - Aggressive angiomyxoma of scrotum.
AB  - Aggressive angiomyxoma is a rare, locally aggressive but non-metastasizing soft
      tissue tumour which occurs almost, exclusively in female pelvic soft tissues. We
      report on a tumour occurring in the scrotum of the adult male. Despite a
      histologically benign picture, wide excision and strict postoperative control are
      recommended because of the risk of tumour recurrence.

PMID- 9764462
TI  - [Transsphenoidal hypophysectomy for the treatment of dogs with pituitary
      dependent hyperadrenocorticism].

PMID- 9764463
TI  - [Serpulina hyodysenteriae infections in swine].

PMID- 9764464
TI  - [NCI policy and veterinary medical practice automatization].

PMID- 9764465
TI  - [Veterinary medicines supplied directly to breeders].

PMID- 9764466
TI  - The optical activity of lysozyme crystals.
AB  - The components of the gyration tensor of the enzyme lysozyme were measured by
      using the HAUP method: g11 = -0.90 x 10(-5) and g33 = 1.05 x 10(-5) at 303.4 K
      and a wavelength of 4880 A. The optical rotatory powers along the a and c axes in
      the same conditions were calculated: rho a = -21.3 and rho c = -24.8 degrees cm
      1. The optically active property of lysozyme is strange in that, although it
      contains a considerable quantity of alpha-helices (about 30%), the rotatory
      powers are unexpectedly small in magnitude, one order of magnitude less than
      those of quartz and with very large anisotropy. A conceptual consideration of
      this phenomenon is given. In order to assess the difference between the
      structures in both crystalline and solution states, the chirality index r was
      calculated to be 0.16. This value indicates that the structural change of
      lysozyme from the solution into the crystalline state is expressed by an increase
      of 19% in optical activity. From the NMR results [Smith et al. (1993), J. Mol.
      Biol. 229, 930-944], it is anticipated that the r value reflects the increased
      constraint in atomic motion in the side chains of exposed amino acid residues in
      the crystalline state.

PMID- 9764467
TI  - X-ray diffraction by a one-dimensional paracrystal of limited size.
AB  - An explicit equation for X-ray diffraction by a finite one-dimensional
      paracrystal is derived. Based on this equation, the broadenings of reflections
      due to limited size and disorder are discussed. It depicts the paracrystalline
      diffraction over the whole reciprocal space, including the small-angle region
      where it degenerates into the Guinier equation for small-angle X-ray scattering.
      Positions of diffraction peaks by paracrystals are not periodic. Peaks shift to
      lower angles compared to those predicted by the average lattice constant. The
      shifts increase with increasing order of reflections and degree of disorder. If
      the heights and widths of the paracrystalline diffraction are treated as reduced
      quantities, they are functions of a single variable, N1/2 g. The width of the
      first diffraction depends mostly on size broadening for a natural paracrystal,
      where N1/2 g = 0.1-0.2. A method to measure the paracrystalline disorder and size
      using a single diffraction profile is proposed based on the equation of
      paracrystal diffraction. An initial value of size may be obtained using the
      Scherrer equation, that of the degree of disorder is then estimated by the alpha
      * law. Final values of the parameters are determined through least-squares
      refinement against observed profiles. An equation of diffraction by a
      polydisperse one-dimensional paracrystal system is presented for 'box'
      distribution of sizes. The width of the diffraction decreases with increasing
      breadth of the size distribution.

PMID- 9764468
TI  - Mechanism of action and the substrate-dependent pH maximum shift of the alpha
      amylase of Bacillus coagulans.
AB  - The alpha-amylase of Bacillus coagulans is a saccharifying alpha-amylase which
      hydrolyses the disaccharide maltose [L. Keating, C. Kelly, and W. Fogarty,
      Biochem. Soc. Trans., 24 (1996) 44S]. The pH maximum for maltose hydrolysis is pH
      5.0, differing from the pH maximum for starch hydrolysis which is pH 6.0. Studies
      using reducing end 14C-labeled maltooligosaccharides revealed a substrate
      dependent pH maximum shift; hydrolysis of radiolabeled maltotriose (G3*) was
      maximal at pH 5.0 while the pH maximum for hydrolysis of radiolabeled
      maltopentaose (G5*) and maltohexaose (G6*) was pH 6.0. With maltotetraose (G4*)
      however, the pH maximum was pH 5.0-6.0. In addition, the bond cleavage pattern of
      G4* was dependent on pH. At pH 5.0, the pH maximum for maltose hydrolysis, the
      frequency of hydrolysis of the reducing end terminal bond of G4* was maximal.
      Determination of the pH maximum of the productive binding modes of the cleavage
      patterns of G3* to G6* illustrated the possible role of the occupation of subsite
      r + 2 in the pH control mechanism of B. coagulans alpha-amylase.

PMID- 9764469
TI  - Evidence for intermolecular binding between deacetylated acetan and the
      glucomannan konjac mannan.
AB  - Binary mixtures of deacetylated acetan and konjac mannan form thermoreversible
      gels under conditions for which the individual components do not gel. Such
      synergistic behaviour is normally attributed to intermolecular binding between
      the two polysaccharides. X-ray diffraction data obtained from oriented fibres
      prepared from deacetylated acetan-konjac mannan gels provides direct evidence for
      intermolecular binding between the two polysaccharides. The novel heterotypic
      junction zones appear to be six-fold helices with a pitch of 5.6 +/- 0.1 nm.

PMID- 9764470
TI  - First analytical chemistry study on drug abuse in the Buenos Aires (Argentina)
      University students.
AB  - One hundred samples were randomly selected from urine specimens collected from
      Buenos Aires University students, 50 males and 50 females, whose ages ranged from
      19 to 47 years. Cocaine (COC), cannabinoids (CNNs), amphetamines (AMs),
      benzodiazepines (BZDs), barbiturates (BBTs), opiates (OPs) and salicylates (SAs)
      were searched for by ELISA, FPIA, normalized TLC, HPLC and GC/MS techniques. The
      presence of COC was detected in five samples, CNN in two and SA in twelve. No
      evidence of AMs, BZDs, BBTs or OPs was found.

PMID- 9764471
TI  - Synthesis of some new biologically active thiadiazolotriazinones.
AB  - 4-Amino-6-arylmethyl-3-mercapto-1,2,4-triazin-5(4H)-ones 1 are condensed with
      aromatic carboxylic acids, aryloxyacetic acids and anilinoacetic acids 2 to yield
      7-substituted-3-arylmethyl-4H-1,3,4-thiadiazolo[2,3-c]-1,2,4-tr iazin-4-ones 3.
      Phosphorus oxychloride is used as cyclizing agent. Some of the newly synthesized
      compounds are screened for their antibacterial activities.

PMID- 9764472
TI  - Synthesis and pharmacological properties of some quinoline derivatives.
AB  - A series of 2-(2-thienyl) cinchoninic acids 3, their derivatives 5 and 4-(3
      substituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazolo-6-yl)-2-( 2-thienyl)
      quinolines 6 were synthesized. The structures of the newly synthesized compounds
      are confirmed by analytical, IR, NMR and mass spectral data. The newly
      synthesized compounds were evaluated for their anti-inflammatory, analgesic and
      anthelmintic activity. The results indicated that dinitrothiophene derivatives 5
      are more active.

PMID- 9764473
TI  - Glycosidopyrroles. Part 3. Effect of the benzocondensation on acyclic
      derivatives: 1-(2-hydroxyethoxy) methylindoles as potential antiviral agents.
AB  - The new of 1-(2-hydroxyethoxy)methylindole derivatives 3a-i were prepared in good
      yields. None of them showed any significant anti-HIV activity and therefore the
      benzocondensation between the 2 and 3 positions of the pyrrole ring definitely
      reduced the weak activity found in the analogues 1a-c.

PMID- 9764474
TI  - Synthesis of some new benzimidazolecarboxamides and evaluation of their
      antimicrobial activity.
AB  - A series of 1,2-disubstituted benzimidazole-5(6)-carboxamides was prepared and
      evaluated in vitro for antimicrobial activity against Staphyloccus aureus,
      Escherichia coli and Candida albicans. The precursor benzimidazolecarboxylic
      acids 4a-c and 9a-c were prepared via oxidative condensation of diaminobenzoic
      acids with aldehydes and via several steps over the 2(1H)-benzimidazolones,
      respectively. All acids were converted to their acyl chlorides with SOCl2, then
      amidified with several N,N'-dialkylaminoethyl derivatives. Compounds 8a-c, 20 and
      22 exhibited the best activity.

PMID- 9764475
TI  - Acute and chronic antiinflammatory effects of plant flavonoids.
AB  - The antiinflammatory activities of 30 flavonoids isolated from several plants of
      the Compositae family were investigated using carrageenan-induced mouse paw edema
      and cotton pellet-induced rat granuloma. Compounds were administered with a
      unique dose of 75 mg/kg i.p. in the acute test with carrageenan and 25 mg/kg/day
      in the chronic granuloma test. Flavonoids inhibit the development of the induced
      granuloma, mostly when a catechol or guaiacol-like B ring is contained in the
      compound structure, jaceosidin being the most active flavonoid screened.
      Flavonoids significantly inhibited the maximum edema response in the acute test.
      We conclude that several of the isolated flavonoids tested here showed
      antiinflammatory effects, depending on the experimental model used.

PMID- 9764476
TI  - Synthesis and antimicrobial activity of coumarin 7-substituted cephalosporins and
      sulfones.
AB  - Some coumarin 7-substituted cephalosporins and related sulfones were prepared and
      an antimicrobial assay was performed. The minimum inhibitory concentration (MIC)
      and minimum bactericidal concentration (MBC) carried out on cephalosporins showed
      a potential activity of some of the synthesized compounds against Gram-positive
      microorganisms. The tests performed on the corresponding sulfones showed no
      significant activity, neither as antimicrobial agents nor as inhibitors of beta
      lactamase. An association of sulfone 6a with ampicillin was observed to inhibit
      Gram-positive microorganisms with a lower MIC than for ampicillin alone.

PMID- 9764477
TI  - Synthesis and biological properties of a new series of N-pyrido substituted
      tetrahydrocarbazoles.
AB  - A series of methyl and ethyl quaternary pyridiniumtetrahydrocarbazoles was
      synthesized and studied in comparison with ellipticine, chosen as a reference. In
      general, their antiproliferative activity, tested in different biological
      substrates, appeared to be higher than that of the corresponding non
      quaternarized compounds. This fact could be attributed to the introduction of a
      positive charge in the molecule, which can stabilize the molecular complex they
      form with DNA. In a prokaryotic system, the T2 bacteriophage, both quaternarized
      and non-quaternarized compounds inhibited its infectivity moderately, in a
      similar way to ellipticine. This effect seemed to be connected to a direct
      activity on the virions rather than on the indicator bacteria. In mammalian
      cells, the pyridiniumtetrahydrocarbazoles were more effective. In particular,
      they appeared to be very active in inhibiting DNA synthesis in Ehrlich ascites
      cells; some of them were as effective as ellipticine. However,
      pyridiniumtetrahydrocarbazoles were less active in comparison with ellipticine
      when their capacity for inhibiting the clonal growth in Chinese hamster ovary
      (CHO) cells was tested. A similar picture was obtained studying the formation of
      chromosome aberrations and of sister chromatid exchanges in the same cells. These
      different responses can be explained considering that the data on DNA synthesis
      reflect effects only on DNA replication within a short time, without considering
      any later consequences; on the contrary, in the long-term tests, other events,
      which lead to cell killing or genotoxicity, can take place.
      Pyridiniumtetrahydrocarbazoles damage DNA, inducing double-strand breaks
      efficiently. These observations, together with the data already obtained on
      unsubstituted derivatives, suggest the pyridiniumtetrahydrocarbazoles induce
      antiproliferative and genotoxic effects, very probably by inhibiting
      topoisomerase II.

PMID- 9764478
TI  - Synthesis and aldose reductase inhibitory activity of benzoyl-amino acid
      derivatives.
AB  - A series of N-(4-methoxy, 4-fluoro, 4-trifluoromethyl and 4-nitrobenzoyl)-L-amino
      acids was synthesized and their inhibitory activity towards bovine lens aldose
      reductase (ALR2) was tested.

PMID- 9764480
TI  - Purification and properties of the 5'-3' exonuclease D10A mutant of DNA
      polymerase I from Streptococcus pneumoniae: a new tool for DNA sequencing.
AB  - A D10A mutation was introduced at the 5'-3' exonuclease domain of Streptococcus
      pneumoniae DNA polymerase I by site directed mutagenesis of the polA gene.
      Introduction of the mutation resulted in a drastic decrease of the 5'-3'
      exonucleolytic activity present in the wild-type enzyme. Moreover, the mutation
      at the D10 residue of the pneumococcal polymerase affected the dependency on
      metal activation of its 5'-3' exonucleolytic activity. These results provide
      experimental support for the proposed direct involvement of this Asp residue in a
      metal-assisted 5'-3' exonucleolytic reaction in type I-like bacterial DNA
      polymerases and related bacteriophage 5'-3' exonucleases. The D10A mutant
      polypeptide retained the polymerase activity of its parental enzyme, it is able
      to incorporate correctly nucleotides in a DNA template, and efficiently uses
      labeled and unlabeled nucleotides analogues in DNA sequencing by the dideoxy
      chain-termination method. These characteristics convert this polymerase into a
      useful tool for manual and automatic sequencing.

PMID- 9764479
TI  - Crystallization and stabilization of MB-1, a de novo designed protein for
      optimized feeding technology.
AB  - Milk Bundle-1 is a de novo protein that was designed for application in
      agriculture. It has a high content of selected essential amino acids, and is
      intended to adopt an alpha-helical bundle fold. Crystallization experiments with
      MB-1 have been carried out on the ground and in reduced gravity on board Columbia
      orbiter during mission STS-80. Rather small crystals were obtained (< 0.05 mm) in
      both environments. Among other factors, the lack of stability of purified MB-1
      has been detrimental to crystal growth. We report here on our progress with
      regard to optimizing crystal growth conditions, protein purification and protein
      stability. The first MB-1 mutant we present (MB-1-His) contains a poly-histidine
      tail, allowing the use of metal affinity chromatography for purification. MB-1
      His has been found to keep its original mass for a month at room temperature, a
      spectacular improvement over MB-1. The other mutant (MB-1-Cys) was engineered to
      carry a cysteine residue on a solvent exposed face. The exposed cysteine binds
      readily to p-HMB, and allows for dimerization of MB-1-Cys. The dimer was found to
      be twice as stable as MB-1 during proteolytic degradation studies.

PMID- 9764481
TI  - Expression of recombinant human acid sphingomyelinase in insect Sf21 cells:
      purification, processing and enzymatic characterization.
AB  - Biochemical and structural studies on human acid sphingomyelinase (haSMase)
      depend on the access to homogeneous biologically active enzyme. Due to the low
      abundance of native haSMase (n-haSMase) in human tissue, conventional
      purification strategies are not suitable for the isolation of preparative amounts
      of the enzyme. We describe a novel approach to the functional expression and
      purification of haSMase employing the baculovirus expression vector system.
      Infection of Spodoptera frugiperda 21 cells with recombinant baculovirus encoding
      haSMase leads to the expression of a glycosylated 75 kDa precursor protein, which
      is subsequently processed to an enzymatically active secreted 72 kDa haSMase.
      Variations in N-glycosylation and proteolytic maturation account for the
      difference in molecular mass between mature recombinant (72 kDa) and human
      placental haSMase (75 kDa). N-terminal amino acid sequencing of recombinant
      haSMase (r-haSMase) reveals a 23-residue N-terminal extension compared to the
      placental enzyme. The apparent K(m) and Vmax values for sphingomyelin degradation
      by r-haSMase in a micellar assay system are 32 microM and 0.56 mmol h-1 mg-1,
      respectively. In conclusion, the established baculovirus expression vector system
      provides an efficient tool for the expression and functional characterization of
      haSMase.

PMID- 9764482
TI  - Gene expression in the electrically stimulated differentiation of PC12 cells.
AB  - Cell differentiation of PC12 cells was electrically induced to grow neurites in
      the absence of nerve growth factor (NGF) on the electrode surface, of which
      potential was modulated by a rectangular wave of potential. The electric
      stimulation induced the c-fos expression which is essential for cell
      differentiation. Non-specific calcium channel blocker, lanthanum ion, inhibited
      the electrically induced differentiation, while NGF-induced differentiation was
      not suppressed. An L-type calcium channel blocker, nifedipine, also inhibited the
      electrically induced calcium influx and c-fos expression. Moreover, a stretch
      activated (SA) channel blocker, gadolinium ion, inhibited the electrically
      stimulated differentiation by blocking the calcium influx, but gave no prominent
      effects on the potassium ion-induced differentiation. Chelerythrine, a specific
      protein kinase C (PKC) inhibitor, almost inhibited the cell differentiation by
      the electric stimulation but not by the NGF treatment. These results indicate
      that the alternative potential may stimulate cell differentiation through a PKC
      cascade.

PMID- 9764483
TI  - Application of an encapsulated filamentous fungus in solubilization of inorganic
      phosphate.
AB  - Spores of Aspergillus niger were encapsulated in agar, calcium alginate and k
      carrageenan and further applied in citric acid production during six repeated
      batch cultivations. Rock phosphate (RP) at concentrations of 3 g l-1 and 7 g l-1
      was supplemented to the culture medium to test encapsulated-fungus solubilizing
      capability. The highest average citric acid productivity of 0.15 g l-1 h-1 was
      reached with alginate-bead-encapsulated A. niger on RP-free culture medium while
      agar seemed to be the most suitable carrier on RP-supplemented medium.
      Accordingly, the highest average soluble P concentration of 0.20 g l-1 batch-1
      was obtained with agar-cell beads as compared with other encapsulated systems.

PMID- 9764484
TI  - Simultaneous multiple analyte detection using fluorescent peptides and capillary
      isoelectric focusing.
AB  - Analyte-specific detection based on the isoelectric point of the detection moiety
      is a new concept that is under investigation at Vysis. We have developed methods
      for the synthesis of of fluorescent synthetic peptides that can be conjugated to
      bioanalytes such as nucleic acids and antibodies, processed in a hybridization or
      binding assay, and then chemically released prior to detection by capillary
      isoelectric focusing (cIEF)-laser-induced fluorescence (LIF) detection. A two
      step cIEF method in coated capillaries using salt mobilization has been used that
      produces high peak efficiencies and good assay reproducibility. The concentration
      by focusing aspect of cIEF, which allows for the entire capillary to be filled
      with sample, enables detection limits in the pM as opposed to sub-nM level for
      conventional capillary electrophoresis (CE)-LIF. The simultaneous multiple
      detection of eleven different focusing entities has been achieved.

PMID- 9764486
TI  - Nonaqueous capillary electrophoresis chiral separations with quaternary ammonium
      beta-cyclodextrin.
AB  - Chiral separation of nonsteroidal anti-inflammatory drugs (profens), 1,1'
      binaphthyl-2,2'-diyl-hydrogen phosphate, N-[1-(1-naphthyl)ethyl]phthalamic acid,
      and derivatized amino acids by a cationic cyclodextrin, quaternary ammonium beta
      cyclodextrin (QA-beta-CD), was investigated by capillary electrophoresis (CE) in
      both aqueous and nonaqueous media. Several profens and amino acids could only be
      separated by QA-beta-CD in pure formamide system. No chiral separation of the
      profens was achieved in the following solvents: N-methylformamide, methanol,
      dimethyl sulfoxide, and water; however, chiral separations of most of the amino
      acids were obtained in all of these solvents. The effects of other experimental
      parameters such as the CD concentration and apparent pH (pH*) were also
      investigated. The first application of nonaqueous CE chiral separation of
      ketoprofen in a commercially available sample, Actron, was also examined. In
      addition, the reversal of electroosmotic flow by QA-beta-CD was observed in
      water, formamide, N-methylformamide, methanol, and dimethyl sulfoxide media.

PMID- 9764489
TI  - Capillary electrophoretic determination of acetic acid and trifluoroacetic acid
      in synthetic peptide samples.
AB  - Synthetic peptide samples may contain counter-ions such as acetate or
      trifluoroacetate as a result of their method of preparation. Furthermore, because
      acetic acid (HOAc) and trifluoroacetic acid (TFA) are frequently used reagents in
      peptide synthesis, these acids may be found in synthetic peptide samples as
      impurities. This paper describes a method validation to determine HOAc and TFA in
      synthetic peptide samples by capillary electrophoresis (CE) using an internal
      standard (I.S.) with indirect UV detection. Typical analytical parameters such as
      precision, linearity, accuracy, specificity, limit of detection and ruggedness
      were evaluated during the validation. In addition, the contents of HOAc and TFA
      in two synthetic opioid peptide samples, TIPP[psi] and Orphanin FQ, were
      determined using the validated method. A unique feature of the method is that it
      offers determination of both acids in a single assay using a common I.S. The
      method is very efficient because of relatively short electrophoretic migration
      times (typically 2 to 8 min) for the acids investigated. This paper also
      discusses the factors that affect precision in a CE assay.

PMID- 9764490
TI  - Optimizing separation conditions for proteins and peptides using imaged capillary
      isoelectric focusing.
AB  - Separation conditions for antibodies, glycoproteins and peptides were optimized
      to fully realize the potential of automated imaged capillary isoelectric focusing
      (imaged cIEF) for protein analysis. Two commercially available capillary
      coatings, polyacrylamide and fluorocarbon, were found to provide reproducible
      results for cIEF separations. Both coatings could last more than 100 runs under
      normal cIEF conditions. Up to 30 mM salts (Na+) could be added to samples to
      prevent protein precipitation before and during isoelectric focusing performed
      under imaged cIEF. Short analysis time of the imaged cIEF also aided in the
      prevention of protein precipitation. High current at the beginning of the
      focusing for samples in salt could be avoided by applying a voltage gradient.
      Additions of up to 6 M urea and 20% glycerol could enhance solubility of proteins
      and peptide. Imaged cIEF was applied to the quantitation of monoclonal
      antibodies.

PMID- 9764491
TI  - Motif 2 in adenosine kinase homologous ginseng polypeptide showed affinity to D
      ribose by capillary zone electrophoresis and surface plasmon resonance.
AB  - Affinity capillary electrophoresis (ACE) and surface plasmon resonance (SPR) were
      applied to the analysis of anti-lipolytic acidic tetradecapeptide from Panax
      ginseng roots. The ginseng polypeptide (GPP) and modified GPPs were chemically
      synthesized and their affinity to D-ribose and adenosine was examined by ACE and
      SPR. GPP had affinity to D-ribose and adenosine and the binding constants (Kb) to
      GPP were calculated by both methods (Kb = 1.04 x 10(4) mol-1 to D-ribose by ACE
      and Kb = 1.91 x 10(4) mol-1 to adenosine by SPR). Most of the modified GPPs lost
      their affinity to D-ribose and adenosine through substitution or rearrangement of
      the amino acids.

PMID- 9764492
TI  - Quantitation of homocysteine in human plasma by capillary electrophoresis and
      laser-induced fluorescence detection.
AB  - Homocysteine (Hcy) represents a branching point between the transsulfuration and
      transmethylation pathway of methionine. A large increase of plasma concentration
      of Hcy is observed in patients with inherited hyperhomocysteinemia. A moderated
      increase (above 10 microM) is also observed in various pathological conditions,
      such as arterial occlusion, hypertension, hyperlipidemia and chronic renal
      failure. While amino acids were largely studied using capillary electrophoresis
      with UV or laser-induced fluorescence detection (LIF), thiol-amino acids were
      not. In this work we present a new approach for testing homocysteine in human
      plasma using CE-LIF and fluorescein isothiocyanate. The low fluorescence yield of
      the fluorescein thiocarbamyl (FTC) thiol-amino acids limits, probably, the
      sensitivity of the detection to 8 x 10(-10) M (instead of 10(-12) M for FTC
      arginine).

PMID- 9764493
TI  - Determination of the minor whey protein bovine lactoferrin in cheese whey
      concentrates with capillary electrophoresis.
AB  - In our present work we present the determination of bovine lactoferrin in whey
      concentrates as they are typically produced by milk and cheese industry after
      production of cheese. Due to the high total protein content the analysis of whey
      concentrate samples is difficult and even not possible by using capillary zone
      electrophoresis with UV detection. To enhance the detection sensitivity we
      applied a more promising approach by using affinity interactions in combination
      with laser-induced fluorescence detection. By mixing fluoresceine isothiocyanate
      (FITC)-conjugated polyanionic lipopolysaccharide with the mostly positively
      charged lactoferrin we found a significant migration time shift which is clearly
      dependent on the concentration of the added protein. In the second approach we
      developed an immunoassay using FITC-conjugated specific antibody against bovine
      lactoferrin. The results of the immunoassay measurements were compared with data
      obtained by standard enzyme-linked immunosorbent assay analysis.

PMID- 9764494
TI  - Coupling on-line brain microdialysis, precolumn derivatization and capillary
      electrophoresis for routine minute sampling of O-phosphoethanolamine and
      excitatory amino acids.
AB  - In previous papers, we described the analysis of excitatory amino acids (EAAs)
      and catecholamines in microdialysis samples using capillary electrophoresis with
      laser-induced fluorescence detection (CE-LIFD). In the present paper, we report
      that an automated analysis of such samples can be easily achieved by on-line
      coupling of the microdialysis probe with a continuous flow derivatization system
      and a commercially available CE-LIFD apparatus. Because of the short analysis
      time (less than 2 min) and high separation efficiency (100-200,000 theoretical
      plates), high temporal resolution of microdialysis (minute range) is preserved as
      compared to off-line systems, while both EAAs and O-phosphoethanolamine (PEA) can
      be simultaneously detected. This new method has been applied to the measurement
      of these compounds in microdialysis samples from hippocampal slice cultures and
      striatum of anesthetized rats. Extracellular concentrations of EAAs, but not PEA,
      increased during perfusion of a solution containing high K+ or a glutamate uptake
      inhibitor. However, after in vitro ischemia on hippocampal slices, both EAAs and
      PEA concentrations increased, but with different temporal patterns.

PMID- 9764495
TI  - Quantifying biosynthetic human growth hormone in Escherichia coli with capillary
      electrophoresis under hydrophobic conditions.
AB  - A method has been developed which is able to quantitate the content of precursor
      biosynthetic human growth hormone (Pre-bhGH) in the cytosol of E. coli cells
      containing the gene for human growth hormone (hGH). The method uses hydrophobic
      C18 coated capillaries with native biosynthetic human growth hormone (bhGH) as an
      internal standard. This allows for highly robust and precise determinations as
      well as the evaluation of the presence of deamidated forms in the cytosol
      samples. Furthermore, by modifying the running buffer with zwitterionic
      surfactants and an organic modifier, it is possible to detect a related form with
      a three sulfur atom Cys-Cys bridge (trisulfide Pre-bhGH). Thus, a strong tool for
      monitoring the effect of fermentation conditions on the biosynthesis of bhGH is
      obtained.

PMID- 9764496
TI  - Cationic and anionic polymeric additives for wall deactivation and selectivity
      control in the capillary electrophoretic separation of proteins in food samples.
AB  - Both cationic and anionic polymeric additives were used for the capillary
      electrophoretic separation of proteins in food samples. The cationic
      polyelectrolyte polydiallyldimethylammonium chloride was more effective in
      minimizing protein-wall interactions at pH 3 than at pH 7, presumably due to
      greater repulsion between the adsorbed polymer and proteins. Improved resolution
      was observed in the presence of the co-additive sodium octanesulphonate,
      presumably due to ion-pairing interactions with protein sample components. The
      anionic polymer dextran sulfate produced relatively high efficiencies, 120,000
      180,000 theoretical plates, for protein separation, presumably because the
      polymer adsorbed to the capillary wall, rendering the surface more hydrophilic.
      In addition to reduced protein-wall interactions, improved resolution was
      observed, presumably due to analyte-polymer ion-exchange/ion-pairing
      interactions. When poly(vinyl sulphonic acid) was used instead of dextran
      sulfate, broader profiles were obtained and fewer components were resolved,
      presumably due to reduced wall deactivation that is related to the lower
      hydrophilicity of poly(vinyl sulphonic acid).

PMID- 9764498
TI  - Asymmetry of protein peaks in capillary zone electrophoresis: effect of starting
      zone length and presence of polymer.
AB  - The asymmetry of R-phycoerythrin (M(r) = 240,000) peaks in capillary zone
      electrophoresis measured as In[(tm-t1)/(t2-tm)], where tm, t1 and t2 are
      migration times of the peak mode and at the intersection of the peak width at
      half-height with the ascending and descending limbs, respectively, was found to
      undergo a transition from negative to positive values with increasing starting
      zone length. The transition is compatible with a mathematical model of peak
      dispersion which assumes that an interaction of protein with the capillary walls
      governs the evolution of the peak during capillary zone electrophoresis. Models
      assuming a final peak shape defined solely by longitudinal diffusion, or by a
      heterogeneity with regard to mobility or by a conductivity difference between
      analyte zone and background electrolyte, have failed to give rise to a change in
      the sign of peak asymmetry when the starting zone length is varied. The presence
      of polyethylene glycol in the buffer within a concentration range up to 4% does
      not appreciably affect the peak asymmetry regardless of whether the concentration
      regime is dilute or semi-dilute. Above 4% of polyethylene glycol, the asymmetry
      becomes nearly independent of starting zone length, and progressively negative
      with increasing polymer concentration. The concentration range at which the
      transition from negative to positive asymmetry disappears coincides with that at
      which the average mesh size of the polymer network falls below the size of the
      protein.

PMID- 9764499
TI  - Capillary electrophoretic study of the complex formation between DNA and cationic
      surfactants.
AB  - Due to the growing interest in the use of cationic surfactants for the
      construction of liposomal genetic delivery systems, the study of complex
      formation between DNA and quaternary ammonium detergents is of fundamental
      importance. In this context, we undertook the study of this complex formation
      using capillary zone electrophoresis (CZE) with suppressed electroosmotic flow, a
      technique that allowed us to both monitor the change in mobility of DNA as a
      function of added surfactant in a precise and reproducible manner and evaluate
      the potential of CZE to reflect the change in hydrodynamic friction upon binding.
      Nevertheless, CZE must be applied with caution for binding studies where strong
      cooperativity occurs, because of the presence of peak splitting at concentrations
      close to the half-point of binding. Also, a comparison between this experiment
      and Manning's polyelectrolyte transport properties theory on one hand and Tirado
      and Garcia de la Torre expression for hydrodynamic friction of rod-like molecules
      on the other hand is given.

PMID- 9764500
TI  - Simultaneous analysis of various mutations on the 21-hydroxylase gene by multi
      allele specific amplification and capillary gel electrophoresis.
AB  - A detailed study is presented on the detection of various known point mutations
      using polymerase chain reaction (PCR) based multi-allele specific amplification
      (MASA) in conjunction with capillary gel electrophoresis (CGE) separation. The
      resulting PCR products, corresponding to the individual mutations, are labeled
      with ethidium bromide during CGE separation, and detected by laser-induced
      fluorescence. MASA proved to be a novel, fast and cost-effective method for
      simultaneous analysis of multiple known mutation sites, employing more than one
      allele specific primers in a single PCR reaction. It results in coexisting
      amplification of numerous DNA fragments differing in size, which are subsequently
      separated by CGE. In the present study, several point mutations were analyzed
      simultaneously by MASA-CGE on the 21-hydroxylase gene of a patient with
      congenital adrenal hyperplasia.

PMID- 9764501
TI  - Pluronic copolymer liquid crystals: unique, replaceable media for capillary gel
      electrophoresis.
AB  - Liquid crystalline solutions of Pluronic copolymers are versatile alternatives to
      solutions of entangled, random coil polymers as replaceable media for capillary
      gel electrophoresis (CGE). Pluronic copolymers are tri-block polymers of
      poly(ethylene oxide) [(EO)x] and poly(propylene oxide) [(PO)y] with the general
      formula (EO)x(PO)y(EO)x. Large micelles form in aqueous solutions in which
      central, hydrophobic cores of (PO)y segments are surrounded by "brushes" of
      hydrated (EO)x tails. Solutions of Pluronic F127 (BASF Performance Chemicals) in
      a concentration range of about 18-30% are liquids at refrigerator temperatures (<
      or = 5 degrees C) and are easily introduced into capillaries. A self-supporting,
      gel-like liquid crystalline phase is formed as the temperature is raised to > or
      = 20 degrees C. This liquid crystalline phase consists of spherical micelles with
      diameters of 17-18 nm which pack with local cubic symmetry. CGE in Pluronic F127
      liquid crystals separates species within several chemical classes as varied as
      nucleoside monophosphates and organic dyes, oligonucleotides of 4-60 nucleotides,
      DNA fragments of 50-3000 base pairs (bp), and supercoiled plasmid DNAs of 2000
      10,000 bp. Mechanisms of molecular sieving in polymer liquid crystals must differ
      in fundamental ways from separations in random polymer gels because molecules
      move around uncrosslinked obstacles that are larger than the smallest dimensions
      of typical analytes. Molecular sieving in Pluronic liquid crystals is envisioned
      to occur as molecules squeeze between hydrated (EO)x strands of micelle brushes,
      or through brushtips and interstitial spaces between micelles. Small molecules
      such as nucleotides appear to separate by a different mechanism involving
      partitioning between hydrophilic and hydrophobic environments. This process is
      termed "hydrophobic interaction electrophoresis". The unique structures of
      Pluronic copolymers and their liquid crystalline phases provide new challenges
      and opportunities in separations science.

PMID- 9764502
TI  - Quality control of pentosane polysulfate by capillary zone electrophoresis using
      indirect detection.
AB  - Pentosane polysulfate sodium salt (PPS) is a mixture of multiply charged anionic
      polysaccharides, used for urological treatment. Several constituents of the
      polysaccharide can be characterized by a highly reproducible fingerprint. In
      comparison with earlier approaches the separation efficiency has been further
      improved using an anionic benzene-1,2,4-tricarboxylic acid buffer (8.7 mmol l-1,
      pH = 4.9) with indirect UV detection (lambda = 217 nm) and a special capillary
      pretreatment (1 M NaOH for 10 h at 25 degrees C applying -20 kV). The method has
      been optimized with regard to buffer concentration and pH. The robustness was
      tested on several capillaries. PPS was separated from all major synthetic
      impurities such a sulfate, chloride and acetate. Twelve PPS batches from two
      manufactures were measured and compared.

PMID- 9764503
TI  - Development of an on-line preconcentration method for the analysis of pathogenic
      lipopolysaccharides using capillary electrophoresis-electrospray mass
      spectrometry. Application to small colony isolates.
AB  - The present investigation describes the use of on-line chromatographic
      preconcentration coupled to capillary zone electrophoresis-electrospray mass
      spectrometry (cPC-CZE-ES-MS) for trace level analysis of negatively charged
      lipopolysaccharides (LPS) obtained from pathogenic strains of Haemophilus
      influenzae. The analytical performance of two different types of adsorption media
      [i.e., C18 irregular particles and poly(styrene-divinylbenzene) membrane] for
      anionic analytes was first evaluated using a mixture of peptide standards to
      determine the overall sensitivity of this approach. These chromatographic
      preconcentrators provided an enhancement of sample loadings of up to 5
      microliters with good linear response and low nM concentration detection limits
      for most peptides investigated. The application of cPC-CZE-ES-MS is further
      demonstrated for extracts of O-deacylated LPS obtained from H. influenzae strain
      Eagan. In combination with novel enzymatic releasing methods using proteinase K,
      this technique provides unparalleled sensitivity and enabled the identification
      of LPS surface antigens from as little as five bacterial colonies.

PMID- 9764504
TI  - Determination of allantoin in biofluids using micellar electrokinetic capillary
      chromatography.
AB  - A micellar electrokinetic chromatographic method is described for the
      determination and quantitation of allantoin, an end-product of purine metabolism
      in mammals that is applicable to biofluids of different mammal species and man.
      The method was optimised following a study on the effect of pH and sample
      preparation procedure. Final conditions were 30 mM sodium tetraborate, pH 9.5, 75
      mM sodium dodecyl sulphate, 20 kV and 20 degrees C. Allantoin was well resolved
      from endogenous compounds and could be determined in horse, dog, mouse and rabbit
      urine. No allantoin could be found in man. No complicated sample treatment was
      necessary, thus the developed method was rapid (< 5 min), sensitive (5 microM)
      and simple. Results from this work will permit the determination of allantoin in
      man as a measure of free radical generation reactions as well as its presence in
      the plasma and other biofluids with modification of the sample preparation
      procedures.

PMID- 9764505
TI  - Capillary electrophoretic study of individual exocytotic events in single mast
      cells.
AB  - In this work we have demonstrated the application of on-column dynamic release of
      serotonin from individual granules within rat peritoneal mast cells (RPMCs).
      These granules are approximately 0.25 fl in volume and represent some of the
      smallest entities studied by capillary electrophoresis (CE). With the coupling of
      high-speed CE and laser-induced native fluorescence, a time resolution of 0.002
      min and a detection limit of 0.9 amol (S/N = 3, rms) were achieved. By using a
      secretagogue as the running buffer for CE, we resolved the peak profile of
      individual degranulation events released due to exocytosis. The average amount of
      serotonin released for five RPMCs analyzed was 33 amol +/- 16%.

PMID- 9764506
TI  - Electrochemical analysis of clinical blood-gases, gases and vapours.
AB  - This tutorial review charts the development of electrochemical sensors for the
      analysis of blood-gases, gases and vapours in clinical medicine over the past
      four decades. The development of each sensor is set in its historical and
      clinical context, and the first part of the review concentrates on aqueous
      electrolyte electrochemistry and on those sensors which have made a major impact
      on the clinical measurement of the partial pressures of oxygen and carbon dioxide
      in the blood. The electrochemical interference effects of anaesthetic agents on
      these measurements are also described. Those electrochemical sensors which have
      failed, in the past, to make a clear impact in this area are not considered, but
      the few attempts to devise aqueous electrolyte electrochemical sensors for
      anaesthetic agent measurement are reviewed. The second part of the review
      describes the chequered history of the development of non-aqueous solvent
      electrochemical sensors to measure the partial pressures of oxygen and carbon
      dioxide, in both the presence and absence of each other, in the gas phase. The
      last part of the review examines various attempts, using non-aqueous solvent
      electrochemistry, to measure the concentration of inhalational anaesthetic
      vapours in the gas phase. These sensors have yet to make an impact on clinical
      practice. Throughout this tutorial review, theoretical models of membrane-covered
      electrochemical sensors are described where appropriate. This review represents a
      personal view of the development of electrochemical sensors for clinical
      measurement, and it is therefore necessarily selective in its approach and
      emphasis.

PMID- 9764507
TI  - Determination of total mercury in biological tissues by flow injection cold
      vapour generation atomic absorption spectrometry following tetramethylammonium
      hydroxide digestion.
AB  - A simple, rapid and reliable method was developed for the determination of total
      mercury in biological samples. Samples were solubilized using tetramethylammonium
      hydroxide (TMAH). The organically bound mercury was cleaved and converted to
      inorganic mercury by on-line addition of KMnO4. The decomposed mercury together
      with inorganic mercury originally present in samples was determined by flow
      injection cold vapour atomic absorption spectrometry after reduction to elemental
      mercury vapour using NaBH4. A sample throughput of 100 measurements per hour was
      achieved after a 30 min dissolution with TMAH. The relative standard deviation
      for 20 micrograms l-1 Hg was 1.3% (n = 11) and the limit of detection was 0.1
      microgram l-1 (3 sigma). The proposed method was validated by the analysis of a
      suite of certified marine biological reference materials, DORM-2 (dogfish
      muscle), DOLT-2 (dogfish liver) and TORT-2 (lobster hepatopancreas), with
      calibration against simple HgII standards.

PMID- 9764508
TI  - Determination of tylosin residues in pig tissues using high-performance liquid
      chromatography.
AB  - In accordance with the maximum residue limit of 100 micrograms kg-1 established
      by EU legislation, a simple and sensitive high-performance liquid chromatographic
      (HPLC) method was developed for the measurement of tylosin residues in pig
      tissues (fat, kidney, liver and muscle). Tylosin, a macrolide antibiotic, is
      extracted with water-methanol and cleaned-up by solid-phase extraction (SPE) on
      cation-exchange cartridges using methanol elution. Tylosin was determined by
      reversed-phase HPLC with UV detection at 280 nm and the mean recovery from pig
      tissues fortified in the range 50-200 micrograms kg-1 was 70-85%, with intra- and
      inter-day RSDs in the ranges 3.4-9.1 and 3.9-10.1% respectively.

PMID- 9764509
TI  - Expression immunoassay based on antibodies labeled with a deoxyribonucleic acid
      fragment encoding the alpha-peptide of beta-galactosidase.
AB  - An immunoassay is reported which uses, as a label, an expressible DNA fragment
      encoding the alpha-peptide of beta-galactosidase. This inactive peptide consists
      of 97 amino acid residues containing an amino-terminal portion of the enzyme.
      Antigen (an anti-thyrotropin immunoglobulin) immobilized in microtiter wells is
      allowed to react with specific antibodies which are then linked to the DNA label
      via biotin-streptavidin interaction. After completion of the immunoreaction, the
      solid phase bound DNA is subjected to a cell-free, one-step
      transcription/translation reaction to produce the alpha-peptide. The alpha
      peptide is allowed to react (complementation reaction) with the remaining part of
      the beta-galactosidase (M15 protein, also inactive) to give fully active enzyme
      molecules. 4-Methylumbelliferyl galactoside is used as a substrate. The
      fluorescence is linearly related to the amount of antigen in the well. As little
      as 3 fmol of antigen can be detected. The RSDs (within-run) obtained for 8 and 20
      fmol of antigen were 10.7 and 9.3%, respectively (n = 4). The present work
      illustrates the utility of expressing a non-detectable peptide capable of
      triggering a signal generating system.

PMID- 9764510
TI  - Sandwich-type deoxyribonucleic acid hybridization assays based on enzyme
      amplified time-resolved fluorometry.
AB  - We report microtiter well-based sandwich-type DNA hybridization assays using
      enzyme amplified time-resolved fluorometry of Tb3+ chelates. The target DNA was
      hybridized with two adjacent and non-overlapping oligonucleotide probes, one
      oligonucleotide serving as the capture probe and the other as the detection
      probe. Two ligand-specific binding protein pairs were used alternately for
      capture of the hybrids to the solid phase and detection; the biotin-streptavidin
      and the digoxigenin-anti-digoxigenin interaction. In both cases, alkaline
      phosphatase was used as a reporter molecule and diflunisal phosphate as a
      substrate. The catalytic hydrolysis of the substrate produces diflunisal which
      forms ternary fluorescent complex with Tb(3+)-EDTA. Furthermore, we studied the
      effect of the probe labeling method and the position of the label on the
      sensitivity of the assays. The data suggest that capture of the hybrids through
      biotin-streptavidin and detection via digoxigenin-anti-digoxigenin offer 2-3
      times higher sensitivity than the reverse configuration. The highest sensitivity
      was achieved with enzymatic labeling of capture and detection probes at the 3'
      end. A signal-to-background ratio of 4 was achieved for 0.2 fmol of target DNA.
      The RSD were better than 4%.

PMID- 9764511
TI  - Development of a biparametric bioanalyser for creatinine and urea. Validation of
      the determination of biochemical parameters associated with hemodialysis.
AB  - The construction and evaluation of an automated urea and creatinine biparametric
      biosystem using flow injection analysis (FIA) are described. The biosystem uses
      enzyme reactions that hydrolyse urea and creatinine producing ammonium ions. The
      enzymes used were creatinine deiminase and urease, which are immobilized
      covalently in flow reactors. The reactor with creatinine deiminase has the enzyme
      immobilized on controlled-pore glass beads, whereas urease is immobilized on a
      nylon open tubular reactor. Detection is realised with a flow-through ammonium
      ion-selective electrode with an inner solid-state contact (graphite-epoxy
      composite). Ammonium ions are separated from alkali ion interferents through a
      gas-diffusion cell. The bioanalyser is fully automated using software and
      electronics developed ex profeso in our laboratories. The analyser was validated
      off-line by measuring urea and creatinine from discrete effluent samples from
      hemodialysis equipment. Results agreed with concurrent analyses realised using
      hospital laboratory methods. There were no significant differences between the
      two sets of results at the 95% confidence level. Finally, the biparametric
      bioanalyser was validated on-line by measuring creatinine and urea levels in
      artificial kidney effluents. These measurements were useful in the determination
      of key biochemical parameters of clinical interest such as the mass of urea and
      creatinine extracted from the patient as well as the initial concentration of
      creatinine and urea in blood plasma. When the results of the bioanalyser were
      compared with those yielded by the usual methods, they showed no significant
      differences at the 95% confidence level when determining the mass of the analytes
      extracted by the hemodialyser or when determining the urea concentration in blood
      plasma. However, when measuring the creatinine concentration in blood plasma
      using the developed bioanalyser, significant differences appeared.

PMID- 9764512
TI  - Liposome immunoassay by long-lived fluorescence detection.
AB  - Immunoassay by fluorescence energy transfer from a europium chelate in liposome
      to allophycocyanin (APC) was demonstrated. Streptavidin or antibody to biotin was
      bonded to the liposome containing the europium chelate of 2
      naphthoyltrifluoroacetone in the bilayer. When the biotin bonded to APC (APC-BT)
      was added to the prepared liposomes and the long-lived fluorescence (lambda ex
      336 nm, lambda em 665 nm, delay time 0.05 ms, gate time 3.9 ms) was measured by a
      flow system, the fluorescence energy of the europium chelate was found to be
      transferred to APC-BT and the long-lived fluorescence intensity to increase
      linearly as the concentration of APC-BT (1-10 micrograms ml-1) increased.
      Further, the intensity decreased competitively with the concentration of biotin
      (0.1-100 microM) when biotin was added to the liposome solution containing a
      constant concentration of APC-BT.

PMID- 9764513
TI  - Electrooxidation of thiocyanate on the copper-modified gold electrode and its
      amperometric determination by ion chromatography.
AB  - Cyclic voltammetry was used to investigate the electrochemical behavior of an
      Au/Cu electrode towards the electrooxidation of thiocyanate ion in alkaline
      medium. The effects of pH, copper loading, scan rate and applied potential on the
      electrocatalytic oxidation of thiocyanate have been investigated. Flow injection
      experiments and ion-chromatography (IC) were performed to characterise the
      electrode as an amperometric sensor for the thiocyanate determination. The
      effects of carbonate concentration and common interferents on the retention time
      were also estimated. The electrode stability, precision, limit of detection and
      linear range were evaluated at a constant applied potential of 0.7 V vs. Ag/AgCl.
      Calibration plots, obtained in IC, were linear from 1.0 to 195 microM
      (correlation coefficient of 0.9984). The detection limit (LOD) was 0.5 microM (29
      ppb) in a 50 microlitres injection. An example of analytical application, which
      includes the IC separation and detection of thiocyanate ion present in human
      urine, is given.

PMID- 9764514
TI  - Determination of the pH difference across a cell membrane using a methylammonium
      selective membrane electrode.
AB  - A method was developed for determining pH differences across cell membranes using
      a methylammonium-selective membrane electrode, based on monitoring of the pH
      gradient-induced uptake of methylammonium in situ. The methylammonium electrode
      was constructed using calix[6]arene-hexaacetic acid hexaethyl ester as a neutral
      carrier and bis(2-ethylhexyl) sebacate as a membrane solvent in a poly(vinyl
      chloride) membrane matrix. This electrode exhibited a near-Nernstian response to
      methylammonium in the concentration range 2 x 10(-5)-1 x 10(-2) M with a slope of
      58 mV per concentration decade in a buffer solution of 150 mM choline chloride-10
      mM TRIS-HCl (pH 7.5). The limit of detection was 5 x 10(-6) M. In experiments
      using liposomes, the uptake of methylammonium into liposomes occurred effectively
      when the pH of the outside suspension medium was alkaline, and the determination
      of changes in methylammonium concentrations in the outer medium was
      quantitatively related to changes in the pH differences across the liposomal
      membrane. The transmembrane pH differences in Escherichia coli cells were also
      determined by this method.

PMID- 9764515
TI  - Development of a method for the determination of low contents of asbestos fibres
      in bulk material.
AB  - Asbestos is a category 1 carcinogen under the EU classification, but in the
      absence of a method to quantify asbestos in a matrix at the 0.1% level, there has
      been a delay in implementing relevant directives to asbestos. An analytical
      scheme for identification and quantification of asbestos using polarised light
      microscopy (PLM) and phase contrast optical microscopy (PCM) has now been
      developed. When used on artificial mixtures by an experienced laboratory, it
      achieved the required target performance, at 0.1% asbestos concentration by mass
      in a bulk sample, to obtain a result, which with 90% probability, is correct
      within a factor of two. The method of identification by PLM and quantification by
      PCM has been assessed by interlaboratory comparisons. The method begins with an
      initial identification using PLM, and depending on asbestos type and matrix a
      combination of preparation procedures are used to produce the analytical filter.
      A gentle comminution method was used which reduces the risk of overmilling. The
      asbestos mass percentage on the filter is quantified using PCM in combination
      with a PLM attachment for identification of possible non-asbestos fibres. The
      final method is supported by efficient methods for fibre identification for size
      determination and calculation of total fibre volume. A statistical analysis of
      mass concentration estimates was made and the effect of preferred orientation of
      fibres on the analytical filter was quantified.

PMID- 9764516
TI  - The medical film 1897-1997: Part I. The first half-century.
AB  - Medicine has frequently been in the forefront of applying new illustrative media
      to its needs, and cinematographic film is a good example. Within a year of the
      introduction of moving pictures, cine-film was used for medical research and to a
      lesser extent for teaching. The profession took advantage of the spread of
      cinemas by making health education films, and during the first half century of
      cinematography surgeons were keen to have their operations filmed. Medical
      educators were slow to include film in their teaching programmes and several
      organizations were formed to encourage their use. After the Second World War,
      medical films for undergraduate and postgraduate education became accepted until,
      as the medical film reached its centenary, cine-film declined in favour of video
      recordings.

PMID- 9764517
TI  - Planning and producing scientific posters.
AB  - Poster sessions now form an important part of most scientific and medical
      meetings. Traditionally they have been seen by presenters as the poor relation to
      the lecture programme and consequently poster preparation has never been given
      the attention it deserves. This article examines the principles of poster
      production and describes the contribution the illustrator can make to its
      production.

PMID- 9764518
TI  - Large format ink-jet poster production: a case report.
AB  - To complement the services offered by the Medical Illustration Department of
      Frenchay Hospital, Bristol, we decided to look at the possibility of producing
      posters using the ink-jet process. Our designers wanted to use the full scope of
      their computers and software to expand their design talents. The method of
      cutting and pasting sheets of paper onto card seemed old fashioned and denied
      clients the benefit of the exciting techniques that have become available. After
      seeking sponsorship, a drug company gave 8000 Pounds towards setting up the
      department's poster printing service. A Kodak DS1000 printer was installed
      together with Posterjet and Posterworks software and we went into production,
      servicing not only our hospital but others in the area who gave their support for
      the service. High quality photographic reproduction was achieved and clients and
      consultants were very pleased with the results. The designers were happy that
      their skills were being used and interest in this and other services in the
      department have increased. The resulting increased income has helped finance
      other projects. The printer has enabled us also to see output proofs before
      sending work off to be offset printed--a very useful tool and a cost-saving
      process.

PMID- 9764519
TI  - 2000 and out? Computers and the 'millennium time bomb'.
AB  - So what is all this fuss about computers and the year 2000? Is it really a
      doomsday scenario? How will it affect us? This short article seeks to explain the
      problem and its significance to the medical illustration profession.

PMID- 9764520
TI  - Making and using visual and audio recordings of patients. General Medical
      Council.

PMID- 9764521
TI  - The cone/horizontal cell network: a possible site for color constancy.
AB  - Color vision is spectrally opponent, suggesting that spectrally opponent neurons,
      such as the horizontal cells in fish and turtle retinae, play a prominent role in
      color discrimination. In the accompanying paper (Kraaij et al., 1998), it was
      shown that the output signal of the horizontal cell system to the cones is not at
      all spectrally opponent. Therefore, a role for the spectrally opponent horizontal
      cells in color discrimination seems unlikely. In this paper, we propose that the
      horizontal cells play a prominent role in color constancy and simultaneous color
      contrast instead of in color discrimination. We have formulated a model of the
      cone/horizontal cell network based on measurements of the action spectra of the
      cones and of the feedback signal of the horizontal cell system to the various
      cone types. The key feature of the model is (1) that feedback is spectrally and
      spatially very broad and (2) that the gain of the cone synapse strongly depends
      on the feedback strength. This makes the synaptic gain of the cones strongly
      dependent on the spectral composition of the surround. Our model, which
      incorporates many physiological details of the outer retina, displays a behavior
      that can be interpreted as color constancy and simultaneous color contrast. We
      propose that the horizontal cell network modulates the cone synaptic gains such
      that the ratios of the cone outputs become almost invariant with the spectral
      composition of the global illumination. Therefore, color constancy appears to be
      coded in the retina.

PMID- 9764522
TI  - Spectral sensitivity of the feedback signal from horizontal cells to cones in
      goldfish retina.
AB  - The spectral sensitivity of cones in isolated goldfish retina was determined with
      whole-cell recording techniques. Three spectral classes of cones were found with
      maximal sensitivities around 620 nm, 540 nm, and 460 nm. UV-cones were not found
      because our stimulator did not allow effective stimulation in the UV range. The
      spectral sensitivity of the cones closely matched the cone photopigment
      absorption spectra at the long wavelength side of the spectrum, but deviated
      significantly at shorter wavelengths. Surround stimulation induced an inward
      current in cones due to feedback from horizontal cells. The spectral sensitivity
      of this feedback signal was determined in all three cone classes and found to be
      broader than the spectral sensitivity of the cones recorded from, and to be
      spectrally nonopponent. These data are consistent with a connectivity scheme
      between cones and horizontal cells in which the three horizontal cell systems
      feed back to all cone systems and in which all horizontal cell systems receive
      input from more than one cone system.

PMID- 9764523
TI  - Noise removal at the rod synapse of mammalian retina.
AB  - Mammalian rods respond to single photons with a hyperpolarization of about 1 mV
      which is accompanied by continuous noise. Since the mammalian rod bipolar cell
      collects signals from 20-100 rods, the noise from the converging rods would
      overwhelm the single-photon signal from one rod at scotopic intensities
      (starlight) if the bipolar cell summed signals linearly (Baylor et al., 1984).
      However, it is known that at scotopic intensities the retina preserves single
      photon responses (Barlow et al., 1971; Mastronarde, 1983). To explore noise
      summation in the rod bipolar pathway, we simulated an array of rods synaptically
      connected to a rod bipolar cell using a compartmental model. The performance of
      the circuit was evaluated with a discriminator measuring errors in photon
      detection as false positives and false negatives, which were compared to
      physiologically and psychophysically measured error rates. When only one rod was
      connected to the rod bipolar, a Poisson rate of 80 vesicles/s was necessary for
      reliable transmission of the single-photon signal. When 25 rods converged through
      a linear synapse the noise caused an unacceptably high false positive rate, even
      when either dark continuous noise or synaptic noise where completely removed. We
      propose that a threshold nonlinearity is provided by the mGluR6 receptor in the
      rod bipolar dendrite (Shiells & Falk, 1994) to yield a synapse with a noise
      removing mechanism. With the threshold nonlinearity the synapse removed most of
      the noise. These results suggest that a threshold provided by the mGluR6 receptor
      in the rod bipolar cell is necessary for proper functioning of the retina at
      scotopic intensities and that the metabotropic domains in the rod bipolar are
      distinct. Such a nonlinear threshold could also reduce synaptic noise for
      cortical circuits in which sparse signals converge.

PMID- 9764525
TI  - Analysis of the postnatal growth of visual cortex.
AB  - Development and growth of V1 begins during embryogenesis and continues
      postnatally. The growth of V1 has direct implications on the organization of
      features such as the retinotopic map and the pattern of visual cortical columns.
      We have examined the postnatal growth and two-dimensional shape of V1 in macaque
      monkeys, cats, and rats. The perimeter, area, and anterior-posterior length of V1
      were measured from unfolded and flattened sections from neonatal and adult
      animals from each of these species. Although there were substantial differences
      in the overall amount of postnatal growth, from 18% in macaque monkeys to more
      than 100% in cats, in all three species the shape of V1 did not change during
      development. Thus, growth of the mammalian visual cortex is well described as an
      isotropic expansion, so the layout of the global features, such as the
      arrangement of ocular dominance columns and the retinotopic map, does not need to
      change during development. Furthermore, quantification of the shape confirms the
      observations that there is a similar, egg-like oval shape to the visual cortex of
      these mammalian species.

PMID- 9764524
TI  - Developmental expression of the rat rod photoreceptor cGMP-gated cation channel.
AB  - The appearance of cGMP-gated cation channel protein in the postnatal rat retina
      has been studied by fluorescence immunocytochemistry of radial retinal sections
      and immunoblots of retinal membrane proteins. Channel immunoreactivity was first
      detectable with RCNGC1-7H2 monoclonal antibody at postnatal day 7 (PN7) by both
      methods. Immunocytochemical label in retinal sections was localized to the outer
      segments, and immunoreactivity increased with increasing age. We also compared
      the developmental appearance of the cGMP-gated cation channel to that of other
      phototransduction proteins and developmental markers. RET-P2, a monoclonal
      antibody recognizing the 39-kDa rds/peripherin disc protein, first labeled outer
      segments at PN7, coincident with cGMP-gated cation channel expression. Double
      labeling of the same section of PN7 rat retina with RET-P2 and R309 (a polyclonal
      antiserum against the rod cGMP-gated cation channel) revealed identical patterns
      of labelling. Similarly, double labeling with RCNGC1-7H2 and an antibody against
      the rod cGMP-phosphodiesterase gave coincident labeling, suggesting coordinate
      expression mechanisms of phototransduction proteins with each other and with
      outer segment structural proteins.

PMID- 9764526
TI  - Increased absolute light sensitivity in Himalayan mice with cold-induced ocular
      pigmentation.
AB  - Controversy over the relationship between ocular pigmentation and absolute dark
      adapted light sensitivity has persisted for over two decades. Previous
      electrophysiological experiments in hypopigmented mammals (mice, rats, rabbits)
      show increased thresholds in the dark-adapted state proportional to the deficit
      in ocular melanin. Animals with the least amount of ocular melanin have the most
      elevated thresholds. Dark-adapted thresholds in hypopigmented mice show similar
      threshold elevations in behavioral tests. The present study extends these
      findings to show that a specific increase in ocular pigmentation results in the
      converse effect, lowered absolute dark-adapted thresholds. The increase in ocular
      melanin was accomplished by keeping Himalayan mice in the cold (4 degrees C) for
      6 weeks. Himalayan mice (C57BL/6J cH/cH) were compared to black mice (C57BL/6J
      (+/+)) and albino mice (C57BL/6J c2J/c2J) after 6 weeks at either 4 degrees C or
      20 degrees C in 12-h cycling light (<1 cd/m2). The Himalayan mice that were kept
      in the cold exhibited a 44% increase in ocular melanin compared to Himalayan mice
      kept at room temperature. Cold rearing did not effect ocular melanin or visual
      thresholds in control animals (black mice = 10(-5.9) cd/m2 and albino mice = 10(
      4.4) cd/m2). In contrast, the Himalayan mice maintained at 4 degrees C had
      thresholds of 10(-5.7) cd/m2 compared to 10(-5.1) cd/m2 for Himalayan mice kept
      at 20 degrees C. This represents compelling evidence of a direct relationship
      between ocular melanin concentration and absolute dark-adapted light sensitivity.

PMID- 9764527
TI  - Zebrafish visual sensitivity is regulated by a circadian clock.
AB  - We have recently developed a behavioral assay, based on the escape response of
      fish to a threatening object, to analyze quantitatively the visual sensitivity of
      zebrafish. During the course of dark adaptation, we measure the threshold light
      intensity required to evoke an escape response. Under a normal light-dark (LD)
      cycle, thresholds for both the cone and rod systems are considerably lower in
      late afternoon hours than in early morning hours. Over a period of 24 h,
      zebrafish are most sensitive to visual stimuli prior to light off and least
      sensitive prior to light on. Under conditions of constant illumination, this
      rhythm of visual sensitivity persists for several days but is gradually lost. In
      constant light (LL), the rhythm persists 1-2 days; thereafter, visual thresholds
      at all times of the day converge at a level similar to thresholds measured in
      late afternoon hours in control animals. In constant darkness (DD). the rhythm
      persists at least 5 days; thereafter, it dampens to a level about a half-log unit
      less sensitive to that measured in the late afternoon hours in control animals.
      These data suggest that visual sensitivity in zebrafish is regulated by an
      endogenous circadian clock which functions to decrease the visual sensitivity.

PMID- 9764528
TI  - Spectral sensitivity of the goldfish Torus longitudinalis.
AB  - We measured the photopic spectral sensitivity of multiunit activity in the torus
      longitudinalis and optic tectum of goldfish. Since negative contrast stimuli are
      most effective for exciting torus longitudinalis, spiking activity was evoked by
      the shadow of a disc moving through a monochromatic light beam projected upon a
      screen. The amount of activity evoked in torus longitudinalis generally increased
      with the monochromatic stimulus radiance at the same rate for all wavelengths,
      indicating a univariant response. Spiking activity in tectum, however, increased
      at different rates across the spectrum, indicating color-dependent responses. The
      action spectra for torus longitudinalis were all similar and relatively flat as
      expected of a homogeneous, broad-band luminance processing system, and about 1
      log unit more sensitive than the tectal action spectra. The latter generally
      displayed sharp peaks and dips in sensitivity indicative of opponent processing.

PMID- 9764529
TI  - Soluble guanylate cyclase and nitric oxide synthase in synaptosomal fractions of
      bovine retina.
AB  - Cyclic GMP has been shown in recent years to directly activate ion channels in
      bipolar and ganglion cells, and to indirectly regulate coupling between
      horizontal cells, and between bipolar and amacrine cells. In all of these cases,
      the effects of cyclic GMP are mimicked by nitric oxide. An increase in calcium
      concentration stimulates the production of nitric oxide by neuronal and
      endothelial forms of nitric oxide synthase, which in turn activates soluble
      guanylate cyclases, enhancing the synthesis of cyclic GMP. Though some effects of
      nitric oxide do not involve cyclic GMP, the nitric oxide-cyclic GMP cascade is
      well recognized as a signaling mechanism in brain and other tissues. The
      widespread occurrence of nitric oxide/cyclic GMP-regulated ion channel activity
      in retinal neurons raises the possibility that nitric-oxide-sensitive soluble
      guanylate cyclases play an important role in cell-cell communication, and
      possibly, synaptic transmission. Immunohistochemical studies have indicated the
      presence of soluble guanylate cyclase in retinal synaptic layers, but such
      studies are not suitable for determination of the density or quantitative
      subcellular distribution of the enzyme. Microanalytical methods involving
      microdissection of frozen retina also showed the presence of cyclase activity in
      retinal plexiform layers but these methods did not permit distinction between
      nitric oxide-sensitive and insensitive cyclases. In this study, we fractionated
      retinal homogenate into the cytosolic and synaptosomal fractions and investigated
      the specific activity and distribution of soluble guanylate cyclase and nitric
      oxide synthase. The results show that both enzymes are present in the
      synaptosomal fractions derived from inner and outer plexiform layers. The
      synaptosomal fraction derived from inner retina was highly enriched in cyclase
      activity. Nitric oxide synthase activity was also higher in the inner than outer
      retinal synaptosomal fraction. The results suggest that the nitric oxide-cyclic
      GMP system is operational in both synaptic layers of retina and that it may play
      a more significant role in the inner retina.

PMID- 9764530
TI  - Peripheral shift reduces visual sensitivity in cat geniculate neurones.
AB  - The sudden displacement of the retinal image during a saccade raises the visual
      threshold of human observers to foveal stimuli. The fall in visual sensitivity
      observed during this phenomenon, known as saccadic suppression, seems to occur
      very early in the visual processing chain. The lateral geniculate nucleus (LGN)
      is a likely locus for the multiple retinal and extraretinal interactions
      occurring during saccadic eye movements, therefore we used the responses of relay
      cells of adult cats to simulate a psychophysical experiment. We first measured
      the responses of X and Y relay cells (27 X and 13 Y) to central spots of optimal
      size and different contrasts. The spots were presented either alone or time
      locked with the rapid movement of a large, high-contrast peripheral pattern,
      referred to as shift. We measured the percentage of trials on which the relay
      cell fired more spikes when the spot (contrast: 0.03-1.0) was present than when
      it was absent. In experiments with human observers the task was to indicate, by a
      keypress, which of two otherwise identical temporal intervals contained the spot.
      The shift reduces the sensitivity (raises the contrast threshold) of neurones in
      the cat relay cells to brief, stationary targets presented to the receptive-field
      center. The suppression of visual sensitivity is significantly greater in Y cells
      than in X cells (average sensitivity ratios 5.6 +/- 5.4 in Y cells, 1.59 +/- 0.9
      in X cells: P < 0.001, U test). The shift also reduces the sensitivity of human
      observers to the same target. This suggests that the LGN is a potential locus for
      the modulation of visual responses that leads to saccadic suppression.

PMID- 9764531
TI  - Localization of nitric oxide synthase, NADPH diaphorase and soluble guanylyl
      cyclase in adult rabbit retina.
AB  - Nitric oxide (NO) acts as a neuronal messenger which activates soluble guanylyl
      cyclase (SGC) in neighboring cells and produces a wide range of physiological
      effects in the central nervous system (CNS). Using immunocytochemical and
      histochemical stains, we have characterized the NO/SGC system in the rabbit
      retina and to a lesser extent, in monkey retina. Based on staining patterns
      observed with an antibody to nitric oxide synthase (NOS) type I and a
      histochemical marker for NADPH diaphorase, a metabolic intermediate required for
      NOS activity, three major classes of neurons appear to generate NO in the rabbit
      retina. These include two subclasses of sparsely distributed wide field amacrine
      cells, rod and cone photoreceptors, and a subpopulation of ganglion cells.
      Equivalent cell populations were labeled in monkey retina. An antibody to SGC
      (tested only in rabbit retina), labeled large arrays of cone photoreceptors in
      the outer nuclear layer, both amacrine and bipolar cells in the inner nuclear
      layer (INL), as well as populations of neurons in the ganglion cell layer. These
      data suggest that the ability to generate NO is restricted to relatively few
      neurons in the inner retina and to photoreceptor cells in the outer retina; while
      presumptive target cells, containing pools of SGC, are widespread and form
      contiguous fields across the inner and outer nuclear layers (ONL) as well as the
      ganglion cell layer.

PMID- 9764532
TI  - Serotonin receptors modulate rod signals: a neuropharmacological comparison of
      light- and dark-adapted retinas.
AB  - Previous physiological studies have shown that serotonin (5-HT) reciprocally
      modulates ON and OFF channels in the mammalian retina. This study was undertaken
      to determine if the serotoninergic system is exclusively associated with the rod
      pathway. We tested drugs specific to 5-HT3 receptor, a serotonin-gated ion
      channel, in both dark- and light-adapted retina. Consistent with previous
      studies, we demonstrated that 5-HT3 receptors modulate the light-evoked responses
      of ganglion cells in the dark-adapted state. Moreover, we have extended these
      prior studies and shown that activation of the 5-HT3 receptor is capable of
      completely blocking the light-evoked response of OFF-center cells whereas
      inactivation of the 5-HT3 receptor is capable of completely blocking the light
      evoked responses of ON-center cells. In contrast, in light-adapted retinae,
      serotonin agents failed to have any effect on retinal processing. These data
      suggest that the serotoninergic system in retina is (1) specifically associated
      with rod-related pathways; and (2) exerts a powerful modulatory force over
      information transfer in the retina. Together these observations suggests that
      serotonin plays an important physiological role in modulating retinal processing.

PMID- 9764534
TI  - Electroretinographic evaluation of spectral sensitivity in yellow and silver eels
      (Anguilla anguilla).
AB  - Although differences in visual pigments between developmental stages of the
      European eel are well known, the expected differences in spectral sensitivity
      have not been demonstrated at the electrophysiological level. In fact, one past
      electroretinographic study led to the conclusion that in eels there is no change
      in scotopic sensitivity, with increasing sexual maturity. In the present
      experiments, electroretinograms (ERGs) were recorded from in situ eyecups of
      immobilized eels Anguilla anguilla (L.) caught in coastal running waters. It was
      shown that the ERG b-wave is as good an indicator of spectral sensitivity as the
      unmasked late receptor potential (LRP) which directly reflects the responsiveness
      of photoreceptors. Complete spectral-sensitivity curves, based on b-wave
      thresholds and on thresholds of LRP subsequently isolated by means of sodium
      iodate, have been obtained in the same eel. Using fitted amplitude-log intensity
      functions for threshold calculation, and two models for computer-assisted fitting
      of spectral-sensitivity curves, significant differences in lambda max were found
      between yellow and silver developmental stages of the eel, identified by ocular
      index measurements.

PMID- 9764533
TI  - Comparison of the distribution and somatodendritic morphology of tectotectal
      neurons in the cat and monkey.
AB  - The presence of a commissure connecting the two superior colliculi suggests they
      do not act independently, but the function of the tectotectal connection has
      never been firmly identified. To develop a better understanding of this
      commissural system, the present study determined the distribution and morphology
      of tectotectal neurons in the cat and macaque monkey, two animals with well
      studied, but different orienting strategies. First, we compared the distribution
      of tectotectal cells retrogradely labeled following WGA-HRP injections into the
      contralateral superior colliculus. In monkeys, labeled tectotectal cells were
      found in all layers, but were concentrated in the intermediate gray layer (75%),
      particularly dorsally, and the adjacent optic layer (12%). Tectotectal cells were
      distributed throughout nearly the entire rostrocaudal extent of the colliculus.
      In cats, tectotectal cells were found in all the layers beneath the superficial
      gray, but the intermediate gray layer contained the greatest concentration (56%).
      Labeled cells were almost exclusively located in the rostral half of the cat
      superior colliculus, in contrast to the monkey distribution. In the context of
      the representation of visuomotor space in the colliculus, the distribution of
      monkey and cat tectotectal cells suggests a correspondence with oculomotor range.
      So these neurons may be involved in directing orienting movements performed
      within the oculomotor range. The somatodendritic morphology of tectotectal cells
      in these two species was revealed by homogeneous retrograde labeling from
      injections of biocytin or biotinylated dextran amine into the contralateral
      colliculus. The cell classes contributing to this pathway are fairly consistent
      across the two species. A variety of neuronal morphologies were observed, so
      there is no single tectotectal cell type. Instead, cell types similar to those
      found in each layer, excepting the largest neurons, were present among
      tectotectal cells. This suggests that a sample of each layer's output is sent to
      the contralateral colliculus.

PMID- 9764535
TI  - Interaction between rod and cone signals in responses of lateral geniculate
      neurons in dichromatic marmosets (Callithrix jacchus).
AB  - Parvocellular (P-) and magnocellular (M-) cells in the marmoset LGN can receive
      prominent rod input up to relatively high illuminance levels (Kremers et al.,
      1997b). In the present paper, we quantify rod and cone input strengths under
      different retinal illuminance levels. The stimulus was based on the so-called
      "silent substitution" method. The activities of P- and M-cells of dichromatic
      animals were recorded extracellularly. We were able to adequately describe the
      response amplitudes and phases by a vector summation of rod and cone signals. At
      low retinal illuminance levels, the cells' responses were determined by rod and
      cone inputs. With increasing illuminances the strength of the cone input
      increased relative to the rod strength. But, we often found significant rod
      inputs up to illuminances equivalent to 700 td in the human eye or more. Rod
      input strength was more pronounced in cells with receptive fields at large
      retinal eccentricities. The phase differences between rod and cone inputs suggest
      that the rod signals lag about 45 ms behind the cone signals.

PMID- 9764536
TI  - Nitric oxide modulates cGMP levels in neurons of the inner and outer retina in
      opposite ways.
AB  - In the mammalian retina, neuronal nitric oxide synthase (NOS) is mainly localized
      in subpopulations of amacrine cells. One function of nitric oxide (NO) is to
      stimulate soluble guanylate cyclases which in turn synthesize cGMP. We used an
      antibody specific for cGMP to demonstrate cGMP-like immunoreactivity (cG-IR) in
      bovine, rat, and rabbit retinae and investigated the effects on cGMP levels of
      both exogenously applied NO and of endogenously released NO. We found that cGMP
      levels in inner and outer retina were controlled in opposite ways. In the
      presence of the NO-donors SNP, SIN-1 or SNAP, cG-IR was prominent in neurons of
      the inner retina, mainly in cone bipolar cells, some amacrine and ganglion cells.
      Retinae incubated in IBMX showed weak cG-IR in bipolar cells. Glutamate increased
      cG-IR in the inner retina, presumably by stimulating endogenous NO release,
      whereas NOS inhibitors or GABA and glycine decreased cG-IR in bipolar cells by
      reducing NO release. In somata, inner segments and spherules of rod
      photoreceptors the situation was reversed. cG-IR was undetectable in the presence
      of NO-donors or glutamate, was moderate in IBMX-treated retinae, but increased
      strongly in the presence of NOS inhibitors or GABA/glycine. We conclude that NO
      is released endogenously in the retina. In the presence of NO, cGMP levels are
      increased in neurons of the inner retina, but are decreased in rods.

PMID- 9764537
TI  - Threshold fluctuations on temporally modulated backgrounds: a possible
      physiological explanation based upon a recent computational model.
AB  - When a temporally fluctuating background is rapidly modulated (e.g. 30 Hz), the
      threshold variation of a superimposed flash (the probe) is approximately
      sinusoidal and in phase with the stimulus. But, with low rates of sinusoidal
      modulation (e.g. 1 Hz), the threshold variation is distinctly nonsinusoidal in
      shape. The bases of these aspects of the data, as well as an unmodulated, dc,
      threshold elevation, are poorly understood. Here 30-Hz and 1-Hz conditions are
      simulated using a new model of light adaptation (Wilson, 1997). By assuming that
      the OFF pathway is twice as sensitive as the ON pathway, the model correctly
      captured the key aspects of both conditions. The results suggest that the 1-Hz
      data are mediated by a mixture of ON and OFF pathways while the 30-Hz data are
      largely mediated by the OFF pathway. The probe thresholds on the 30-Hz background
      appear approximately sinusoidal and approximately in phase with the background
      stimulus. A number of factors contribute to this deceptively simple observation.

PMID- 9764538
TI  - Dual expression of GABA or serotonin and dopamine in Xenopus amacrine cells is
      transient and may be regulated by laminar cues.
AB  - Both local cell-cell interactions and lineage bias have roles in determining the
      different retina cell phenotypes. In this study, subpopulations of amacrine cells
      that dually express GABA or serotonin (5-HT) and dopamine (DA) are identified in
      the early Xenopus tadpole (stages 42-48) retina. GABA is first detected by
      immunocytochemistry in amacrine cells at stage 35/36, 5-HT at stage 39, and DA at
      stage 41. As the number of these subtypes of amacrine cells increases by
      differentiation, a subset of them transiently express two neurotransmitters.
      GABA/DA double-labeled amacrine cells are detected first at stage 42, at which
      time they constitute 52% of the DA-containing population; this percentage
      decreases to only 3% by stage 48. 5-HT/DA amacrine cells are detected only at
      stage 44, constituting about 20% of the DA-containing cells and 4% of the small
      dim 5-HT-containing cells. Regional location does not differentially affect the
      differentiation of these three types of amacrine cells (DA only, GABA/DA, and 5
      HT/DA cells); each type is found more in the anterior and dorsal than the
      posterior and ventral quadrants, and their overall distribution patterns are
      statistically indistinguishable. However, these subtypes of amacrine cells reside
      in different sublamina of the inner nuclear layer. DA-only amacrine cells are
      located predominantly in the inner sublayer of the 2-3 cell thick amacrine cell
      layer, closest to the inner plexiform and the ganglion cell layers. Both types of
      double-labeled cells are located mostly in the outer sublayer of the amacrine
      cell layer, closest to other interneurons in the inner nuclear layer. This
      distinct sublaminar location of different neurotransmitter phenotypes suggests
      that local laminar cues influence the coexpression of neurotransmitters in
      amacrine cells.

PMID- 9764539
TI  - Responses of regular spiking and fast spiking cells in turtle visual cortex to
      light flashes.
AB  - Sharp electrodes were used to record light-evoked postsynaptic potentials (PSPs)
      from neurons in turtle visual cortex in an in vitro preparation of the
      geniculocortical pathway. Neurons were placed into four groups based on the
      firing patterns produced by intracellular current injections: regular spiking
      (RS), fast spiking (FS), intrinsic bursting (IB), and chattering (CH) cells. RS
      cells have been shown to be pyramidal cells while FS cells are typically
      interneurons. Light stimuli were diffuse, 1-s flashes of 640-nm light with
      intensities (I) varying from 0 to 10(4) photons microm(-2) s(-1). The response
      (R) in each case was the maximal amplitude of the light-evoked depolarizing PSP.
      Cells of all four types showed sigmoidal intensity-response (IR) functions with a
      linear rising phase for stimuli above the intensity threshold followed by
      saturation at high light intensities. Responses at high intensities were variable
      and some cells showed indications of supersaturation. Light-evoked PSPs had
      longer latencies and times-to-peak response in RS cells than they did in FS
      cells. RS cells fired action potentials as much as 200 ms later than did FS
      cells. Since responses recorded in RS cells at light intensities just above
      threshold are unlikely to involve contributions from other pyramidal cells, these
      data indicate that the geniculocortical or feedforward pathway to pyramidal cells
      has a high gain. The fact that FS cells fire well before RS cells suggests that
      feedforward inhibition plays a role in controlling the gain of the
      geniculocortical pathway.

PMID- 9764540
TI  - Defect repair after somite removal in avian embryos is not true regeneration.
AB  - The question of regeneration after experimental somite extirpation has been
      controversial in the literature. While all workers agree that repair of the
      defects occurs, results concerning the extent and mechanism of this process, as
      well as the origin of the cells filling the defect, show great discrepancies. Our
      approach towards a re-examination of this question involved microsurgical removal
      of individual somites in 2-day-chick embryos in combination with grafting of
      quail somites and lateral plate. We show that the defect in the paraxial mesoderm
      is filled within a day after extirpation and that the reconstituting cells are
      derived only from the cranial and caudal somites, but not from the contralateral
      somites or from the lateral plate. There are no indications of an increase of
      proliferation in the neighbouring somites. In order to examine the
      differentiation capacities of the cells that fill the defect, we used
      immunohistochemistry and in situ-hybridization. We show that the cells in the
      defect are mesenchymal in morphology and express Pax-1 and Twist. There are a few
      desmin-positive cells in the defect that can be shown to derive from adjacent
      somites. An epithelial dermomyotome and myotome are absent at the operation site.
      Neural crest cells do not participate in the reconstitution of the defect. We
      conclude that cells in the defect either already have or adopt a ventral somitic
      (sclerotomal) identity, whereas derivatives with dorsal identity are absent from
      the defect except for a few individual cells.

PMID- 9764541
TI  - Vascularization of embryonic adrenal gland grafted onto chorioallantoic membrane.
AB  - Vascularization and endothelial phenotype expression were analysed in embryonic
      adrenal tissue grafted onto chorioallantoic membrane (CAM), by means of routine
      light microscopy and immunocytochemical staining, and of electron microscopy.
      Adrenal gland tissue from chick or quail embryos (donors) was grafted onto CAMs
      of chick or quail embryos (host). Vessels of chick origin were discriminated from
      those of quail origin by monoclonal antibodies, anti-MB1, specific for quail
      endothelial and haemopoietic cells, and QCPN, which labels quail cell nuclei.
      Vessels of adrenal type were distinguished from those of CAM-type by their
      ultrastructural endothelial phenotype - porous in the former and continuous in
      the latter. The observations carried out 6 days after implantation indicate that
      the adrenal gland develops and differentiates according to a virtually normal
      histological pattern. As regards the adrenal and CAM vascularization, the
      grafting procedure elicits angiogenic events consisting in the formation of
      peripheral anastomoses between the graft and the CAM original microvasculature
      and in new-growth of vessels from the CAM into the grafted tissue and vice versa.
      As to the endothelial phenotype, the ultrastructural results demonstrate that
      besides its own native vasculature, the adrenal tissue contains vessels with
      continuous endothelium and the CAM mesenchyme is supplied by adrenal-type,
      fenestrated vessels.

PMID- 9764542
TI  - Subcellular compartmentation of glutathione and glutathione precursors. A high
      resolution immunogold analysis of the outer retina of guinea pig.
AB  - Selective antibodies were used to assess the cellular and subcellular
      localization of glutathione, and the glutathione precursors gamma
      glutamylcysteine, glutamate, and cysteine, in neuronal (photoreceptors) and non
      neuronal (pigment epithelial cells and Muller cells) cell types in the outer
      retina of the guinea pig. In each cell type the highest level of glutathione
      immunoreactivity occurred in the mitochondria. The labeling density in the
      cytoplasmic matrix was higher (and the mitochondrial-cytoplasmic gold particle
      ratio lower) in pigment epithelial cells than in Muller cells and photoreceptors.
      The latter two cell types showed a mitochondrial-cytoplasmic gold particle ratio
      of 15.5 and 21.7, respectively. In contrast to glutathione, gamma
      glutamylcysteine seemed to be enriched in the cytoplasmic matrix relative to the
      mitochondria. The immunogold labeling for this dipeptide was stronger in the
      pigment epithelial cells than in Muller cells and photoreceptors. Glutamate
      immunoreactivity was high in photoreceptors, intermediate in pigment epithelial
      cells, and low in Muller cells, while the cysteine immunogold signal was low in
      each cell type and cell compartment. The present results suggest that glutathione
      is concentrated in mitochondria but to different degrees in different cells. The
      low mitochondrial content of gamma-glutamylcysteine (the direct precursor of
      glutathione) is consistent with biochemical data indicating that glutathione is
      synthesized extramitochondrially and transported into the mitochondrial matrix.
      Judged from the immunocytochemical data, cysteine may be a rate-limiting factor
      in glutathione synthesis in each cell type while glutamate can be rate limiting
      only in Muller cells.

PMID- 9764543
TI  - Early development of the zebrafish (Danio rerio) pharyngeal dentition (Teleostei,
      Cyprinidae).
AB  - In order to build a reference system to assess ongoing in vitro and in situ
      hybridisation experiments on epithelial-mesenchymal interactions governing
      odontogenesis in the zebrafish, we describe here the generation of the pharyngeal
      dentition, and the histological development of teeth up to fourteen days post
      fertilization, using serial semithin sections, handmade and computer-assisted
      reconstructions and transmission electron microscopy. The tooth pattern in larval
      zebrafish is generated in a predictable, and bilaterally symmetrical manner from
      shortly before hatching onwards. Characteristics related to tooth development and
      structure differ considerably from those seen in juvenile specimens and those
      described for other bony fishes. Particular features related to the cyprinid
      condition include the complex epithelial connectivity and the mode of attachment
      of the teeth.

PMID- 9764544
TI  - Immunoreactivity of the ets-1 transcription factor correlates with areas of
      epithelial-mesenchymal transition in the developing avian heart.
AB  - Cardiac morphogenesis involves substantial remodeling processes that include cell
      transdifferentiation and migration. The c-ets-1 protooncogene codes for a
      transcription factor that can transactivate a number of genes involved in
      developmental processes such as degradation of extracellular matrices and cell
      migration. We have immunolocated the ets-1 protein in the heart of quail and
      chick embryos between the Hamburger and Hamilton stages HH16 and HH37. In HH16-17
      embryos, the ets-1 transcription factor was only detected in some endocardial
      cells and in most mesothelial and mesenchymal cells of the proepicardium. Ets-1
      immunoreactivity increased markedly in the developing endocardial cushions,
      myocardium, epicardium and early subepicardial mesenchyme of HH18-19 embryos. By
      HH20-24 the immunoreactivity was found throughout the heart, with a stronger
      intensity in the areas of epithelial-mesenchymal transition of the endocardium
      and epicardium. In embryos between HH26 and HH33, ets-1 immunoreactivity
      increased in the cushion mesenchyme, atrioventricular endocardium, ventricular
      epicardium and subepicardial mesenchyme cells, but not in other areas of the
      heart. The immunoreactivity declined in the innermost part of the endocardial
      cushions. The subepicardial mesenchyme was particularly immunoreactive in these
      stages, coinciding with the development of the subepicardial vascular network. In
      fact, ets-1 colocalized with the quail vascular marker QH1 in the subepicardial
      mesenchymal cells. Ets-1-negative cells were abundant in the subepicardium and
      valvuloseptal tissue of the HH37 embryos. The results suggest that ets-1,
      probably through transactivation of genes such as urokinase-type plasminogen
      activator and matrix metalloproteinases, might play a crucial role in the
      differentiation of the cushion and subepicardial mesenchyme, the formation of the
      intratrabecular sinusoids and the early development of the cardiac vessels.

PMID- 9764545
TI  - Development of the atrioventricular valve tension apparatus in the human heart.
AB  - Using various microscopical techniques we studied the development of the
      atrioventricular valves in human hearts between 5 and 19 weeks of development.
      Within the atrioventricular cushions two different layers could be recognized
      that remained present in all ages studied. The atrial layer, being present at the
      side of the atrioventricular orifice, was positive for laminin while the
      ventricular layer, that was connected to the myocardium, was positive for
      fibronectin and collagen III. Fate-mapping of these two layers, morphometrics,
      and scanning electron microscopy, supplemented with in vivo labeling of cushion
      tissue in chicken hearts have lead to new insights in the process of valve
      development. The cushions became freely movable prevalvular leaflets by
      delamination of ventricular myocardium underneath the cushion tissue. This
      myocardium gradually retracted towards annulus and papillary muscles and finally
      disappeared, resulting in fibrous, non-myocardial valves. The atrial layer of the
      cushions remained present as a jelly-like surface on the valve leaflets while the
      ventricular layer of the cushions became the compact fibrous tissue of the
      leaflets and the chords. Chordal development was first visible at 10 weeks of
      development when gaps were formed in the ventricular layer of the cushions on top
      of the papillary muscles. These gaps enlarged into the interchordal spaces while
      the cushion tissue in between the gaps lengthened to form the chords. We conclude
      that the leaflets as well as the chords of the atrioventricular valves are
      derived from atrioventricular cushion tissue. Myocardium is only important for
      loosening of the leaflets while keeping connection with the developing papillary
      muscles. Errors in delamination or retraction of myocardium or remodeling of
      cushion tissue into chords form the basis for various congenital valve anomalies.

PMID- 9764546
TI  - Lectin binding patterns in the vomeronasal organ and accessory olfactory bulb of
      the rat.
AB  - A number of previous studies have indicated that lectin histochemistry is an
      obvious choice for characterizing the vomeronasal system. However, apparently
      inconsistent results have been obtained: notably, the affinity with which various
      lectins bind to the accessory olfactory bulb varies among taxa, even considering
      closely related species. In the present study, the binding patterns of seven
      lectins in the rat accessory olfactory bulb, vomeronasal nerves and vomeronasal
      duct were investigated. The Bandeiraea simplicifolia lectin bound exclusively to
      the vomeronasal nerve and glomerular layers of the accessory olfactory bulb,
      while the Ulex europeus and Lycopersicon esculentum lectins bound to these
      regions and additionally to the nerve and glomerular layers of the main olfactory
      bulb. Soybean agglutinin showed a similar pattern to that obtained with the Ulex
      europeus and Lycopersicon esculentum lectins, though it also faintly labelled
      other parts of the structures examined. The Vicia villosa and Erythrina
      cristagalli lectins were not specific for the vomeronasal system, since they
      labelled grey and white matters in structures including the lateral olfactory
      tract and the anterior olfactory nuclei. The Dolichos biflorus lectin did not
      bind to vomeronasal tissues. The observed patterns of binding in the accessory
      olfactory bulb were consistent with those observed in the vomeronasal nerves, but
      unlike those observed in the epithelium of the vomeronasal duct. This latter
      result probably reflects binding of lectins to sugar residues contained in
      secreted mucus rather than those in epithelial nerve endings.

PMID- 9764547
TI  - Risk assessment and risk-based therapy in febrile neutropenic patients.

PMID- 9764548
TI  - Bacterial DNA as an evolutionary conserved ligand signalling danger of infection
      to immune cells.
AB  - During infection, the innate limb of the immune system senses danger (pathogens)
      via constitutively expressed pattern-recognition receptors, and responds with
      activation and secretion of pro-inflammatory cytokines. Cell-wall components of
      gram-positive and gram-negative bacteria, such as peptidoglycan, endotoxin or
      lipoteichoic acid, activate via CD14, a prototypic pattern-recognition receptor
      for carbohydrates. This review article focuses on an alternative recognition
      system of the innate immune system for the recognition of bacterial DNA.
      Bacterial DNA differs from eukaryotic DNA in its frequency of the dinucleotides
      CG and its lack of methylation. These structural differences appear to be sensed
      by cells of the innate immune system such as antigen-presenting cells. As a
      consequence bacterial DNA serves as an alternate ligand to signal danger of
      infection. Bacterial DNA and (synthetic) oligonucleotides (ODN) derived thereof
      are as efficient as endotoxin in activating macrophages and dendritic cells and
      in triggering release of pro-inflammatory cytokines. In mice sensitized with D
      galactosamine (D-GalN), high doses of bacterial DNA from either gram-positive or
      gram-negative pathogens induce a lethal cytokine syndrome (lethal shock).
      Therefore, bacterial DNA may represent a hitherto unrecognized pathophysiological
      entity in host-parasite interactions. Moreover, recent evidence suggests that
      bacterial DNA or immunostimulating ODN triggers the immunostimulation of antigen
      presenting cells, and can be utilized as adjuvant to enhance immune responses of
      the adaptive immune system towards poorly immunogenic antigens. In fact, foreign
      DNA might be useful as immunotherapeutically active adjuvant to direct adaptive
      immune responses towards Thl-dominated immune reactions. If these findings are
      operative in humans, immunostimulating ODN might be used to influence Th2
      dominated diseases such as allergy.

PMID- 9764549
TI  - Multicenter, randomized, double-blind comparison of erythromycin estolate versus
      amoxicillin for the treatment of acute otitis media in children. AOM Study Group.
AB  - Erythromycin is frequently prescribed in Germany for acute otitis media, but well
      designed clinical trials under present epidemiological conditions are lacking.
      Therefore, a double-blind, randomized, multicenter trial was performed to compare
      the clinical efficacy and safety of erythromycin estolate versus amoxicillin in
      children with acute otitis media and to identify the risk factors associated with
      clinical failure. Investigators from 19 centers throughout Germany recruited 302
      children with clinical, otoscopic, and tympanometric evidence of acute otitis
      media. In a double-blind fashion, patients were allocated randomly to a 10-day
      course of erythromycin estolate at 40 mg/kg/day in two divided doses or
      amoxicillin at 50 mg/kg/day in two divided doses. Clinical examinations,
      otoscopy, and tympanometry were performed at baseline, day 3-5, day 9-11, and at
      5 weeks. Clinical outcome was assessed on day 9-11. Two-hundred eighty children
      were evaluable for efficacy (erythromycin group, 141; amoxicillin group, 139).
      Both groups were comparable with respect to demographic data and severity of
      disease at entry. Treatment was successful in 94% of the erythromycin-treated
      patients and in 96% of the amoxicillin-treated patients. Clinical outcome was
      statistically equivalent between groups within a range of 7 percentage points.
      Clinical recurrence was seen in eight erythromycin-treated children (5.7%) and in
      seven amoxicillin-treated children (5.0%) (P=0.81). Patients with bilateral
      disease at entry were at higher risk of unfavourable outcome, whereas age and
      presence/absence of otorrhea at entry were not associated with outcome. Treatment
      related adverse events were recorded in eight (5.3%) of 151 erythromycin-treated
      patients and in 11 (7.3%) of 151 amoxicillin-treated patients. In this study in
      an outpatient setting in Germany, erythromycin estolate was as safe and effective
      as amoxicillin in the treatment of acute otitis media. Both drugs can be
      administered in a convenient twice-daily dosage schedule.

PMID- 9764550
TI  - Evaluation of six commercial systems for identification of medically important
      yeasts.
AB  - Six commercially available systems for the identification of yeasts were
      evaluated using 133 clinical isolates and four reference strains that had been
      previously identified by conventional methods and 19 recent clinical isolates
      that had been identified by the ID32C system (bioMerieux, France). The total
      identification rates (TIR) established for the total number of strains tested and
      the database identification rates (DBIR) established for the strains included in
      the respective manufacturer databases were both determined. After incubation for
      4 h, the TIR and DBIR were 78% and 84%, respectively, for the RapID Yeast Plus
      system (Innovative Diagnostic Systems, USA). After incubation for 24 h, the TIR
      and DBIR were 32% and 32%, respectively, for the ID32C, 65% and 67% for the
      Auxacolor system (Sanofi Diagnostics Pasteur, France), 62% and 65% for the
      Fungichrom I system (International Microbio, France), 52% and 65% for the
      Fungifast I twin system (International Microbio), and 62% and 68% for the API
      Candida system (bioMerieux). The maximum TIR and DBIR (+/- 1%) obtained after
      incubation for 48 h were 86% and 88% for the Auxacolor, 85% and 89% for the
      Fungichrom I, 78% and 98% for the Fungifast I twin, and 82% and 91% for the API
      Candida. For the ID32C, the maximum TIR and DBIR were 98% and 98%, respectively,
      but these values were obtained only after 72 h of incubation. In addition, the
      six systems varied in their ease of use and readings. In conclusion, based on
      results obtained with 156 strains, the Auxacolor and Fungichrom systems seem the
      most appropriate for use in a clinical microbiology laboratory, due to their ease
      of use and reading, their rapidity, their cost per test, and their relatively
      high TIR results, which indicated acceptable performance with strains frequently
      isolated in our hospital. For a reference identification, the ID32C remains the
      sole system usable.

PMID- 9764551
TI  - Use of a selective medium and a membrane filter method for isolation of
      Campylobacter species from Spanish paediatric patients.
AB  - A study was conducted to assess the value of a combination of two culture methods
      for isolation of Campylobacter spp. from Spanish children. Seven hundred twenty
      nine diarrhoeal stool specimens from 599 patients were examined for Campylobacter
      spp. by culturing them on charcoal cefoperazone deoxycholate agar and on blood
      agar with a membrane filter. One hundred sixteen Campylobacter strains were
      isolated from a total of 108 specimens; 75 (64.6%) were Campylobacter jejuni, 32
      (27.5%) were Campylobacter coli, 8 (6.8%) were non-typeable, and one (0.9%) was
      Campylobacter upsaliensis. Campylobacters were isolated from 99 positive samples
      using charcoal cefoperazone deoxycholate agar alone. The filtration technique
      alone yielded only 86 positive samples. Seven specimens yielded different
      Campylobacter spp. with different media. The only catalase-negative strain was
      recovered using the filter method. The combination of the selective medium with
      the filter method increased the isolation rate of Campylobacter strains by 14.1%.
      Isolation rates of campylobacters using the filter method were similar to those
      reported in European studies, in which a similar frequency of Campylobacter
      upsaliensis was observed. The addition of a filter method for routine laboratory
      isolation of campylobacters should be considered in selected age groups (in
      children < 10 years of age) or in areas where catalase-negative or weakly
      positive Campylobacter strains may be of epidemiological significance.

PMID- 9764552
TI  - Use of microscopic morphology in smears prepared from radiometric cultures for
      presumptive identification of Mycobacterium tuberculosis complex, Mycobacterium
      avium complex, Mycobacterium kansasii, and Mycobacterium xenopi.
AB  - The aim of this study was to assess the feasibility of a method for presumptive
      identification of mycobacteria, based on the morphology in smears prepared from
      radiometric Bactec-positive cultures (Becton Dickinson, USA) and to select the
      appropriate DNA probe (AccuProbe; Gen Probe, USA). The smear morphology of acid
      fast bacilli was evaluated in 468 positive cultures from clinical samples: 313
      Mycobacterium tuberculosis complex, 67 Mycobacterium avium complex, 32
      Mycobacterium kansasii, 49 Mycobacterium xenopi, and seven Mycobacterium
      gordonae. The sensitivity and specificity for various morphological patterns were
      as follows: cord formation for Mycobacterium tuberculosis complex 90% and 100%,
      respectively; striped bacilli for Mycobacterium kansasii, 66% and 99%; sea urchin
      for Mycobacterium xenopi, 96% and 99%; short bacilli for Mycobacterium avium
      complex, 61% and 99%; fine-striped bacilli associated with Mycobacterium avium
      complex from blood samples, 33% and 98%. This criterion was applied in the
      selection of a suitable DNA probe for the identification of 178 cultures. The
      correct probe was selected in 98%, 97%, and 72% of cultures, respectively, for
      Mycobacterium tuberculosis complex, Mycobacterium avium complex, and
      Mycobacterium kansasii. The observation of acid-fast bacilli morphology in
      radiometric cultures is a rapid and cost-efficient method for presumptive
      identification of common clinical isolates of mycobacteria.

PMID- 9764553
TI  - Ceftriaxone in the outpatient treatment of cancer patients with fever and
      neutropenia.
AB  - A study was performed in low-risk cancer patients with chemotherapy-induced
      febrile neutropenia to determine the safety and efficacy of ceftriaxone given in
      an outpatient setting. A total of 126 episodes of febrile neutropenia in 120
      clinically stable outpatients were treated with intravenous ceftriaxone alone
      (n=100) or in combination with other antibiotics (n=26). The mean neutrophil
      count was 460/mm3; severe neutropenia (< 100/mm3) was observed in 18 episodes.
      The initial treatment with ceftriaxone (alone or in combination) was successful
      in 99 episodes (78%). Ninety-five episodes (76%) were successfully treated in an
      outpatient setting only; admission to hospital was necessary in 31 episodes
      (24%), but no infection-related death was observed. Ceftriaxone seems to be safe
      and effective for outpatient therapy of patients with low-risk febrile
      neutropenia.

PMID- 9764554
TI  - Stomatococcus mucilaginosus septicemia in a patient with acute lymphoblastic
      leukaemia.
AB  - A 16-year-old patient with acute lymphoblastic leukaemia which had relapsed for
      the third time developed clinical signs and symptoms of septicemia during a
      period of neutropenia. The patient had signs of oral mucositis, and Stomatococcus
      mucilaginosus was isolated from blood cultures. The patient responded well to
      antibiotic therapy. The biochemical characteristics and antimicrobial
      susceptibility patterns of 68 other pharyngeal isolates of Stomatococcus
      mucilaginosus from immunocompromised patients are presented.

PMID- 9764555
TI  - Significance of ahpC promoter mutations for the prediction of isoniazid
      resistance in Mycobacterium tuberculosis.
AB  - To determine the value of ahpC promoter mutations for the rapid prediction of
      isoniazid resistance, this genomic region was characterized in 50 isoniazid
      resistant and 12 isoniazid-sensitive Mycobacterium tuberculosis isolates. Of the
      resistant isolates, 12 had ahpC promoter mutations, but only one possessed both
      an ahpC promoter mutation and a katG codon 315 substitution, although the latter
      was found in the majority (54%) of the isoniazid-resistant isolates investigated.
      This investigation presents empirical evidence that the central portion of the
      ahpC promoter is the most valuable genetic locus to complement katG codon 315
      characterizations in order to increase the sensitivity of molecular tests for the
      prediction of isoniazid resistance.

PMID- 9764556
TI  - Five cases of Kingella kingae skeletal infection in a French hospital.
AB  - Five cases of Kingella kingae skeletal infections were diagnosed in children
      admitted to La Timone Hospital between 1992 and 1997. Patients were between 6 and
      31 months old and presented with septic spondylodiskitis, calcaneus
      osteomyelitis, and hip-joint arthritis. All displayed either an upper respiratory
      tract infection or eczema during the month prior to their admission. Laboratory
      findings included an elevated leukocyte count and an elevated erythrocyte
      sedimentation rate. Standard radiography was unrevealing, but 99mTc bone scans
      and magnetic resonance imaging showed significant abnormalities. Isolation of
      Kingella kingae was achieved in all cases by culture of fluid aspirates using the
      Bactec blood culture system. This bacterium was sensitive to the most common
      antibiotics tested, and the outcome was favourable in all cases.

PMID- 9764557
TI  - Isolation of a novel mycobacterium from an adolescent with cervical
      lymphadenitis.
AB  - A slow-growing mycobacterium was isolated from a cervical lymph node of an
      adolescent male. This isolate produced small, smooth, scotochromogenic colonies
      after 6 weeks of incubation at 25 degrees C and 30 degrees C (but not at 37
      degrees C or 43 degrees C). The results of 16S-rRNA gene sequencing and high
      performance liquid chromatography suggest that this isolate belongs to a hitherto
      unrecognised pathogenic species.

PMID- 9764558
TI  - Prevalence of Helicobacter pylori resistance to several antimicrobial agents in a
      region of Germany.
AB  - To evaluate the prevalence of resistance among Helicobacter pylori in Germany,
      the minimum inhibitory concentrations of amoxicillin, tetracycline,
      clarithromycin, and metronidazole were determined by means of the E test, for 271
      Helicobacter pylori isolates cultured from biopsies taken during routine
      endoscopies in 1996 and 1997. The prevalence of metronidazole resistance was
      32.1%, with resistance found more frequently in women (38.5%) than in men
      (24.4%). Clarithromycin resistance was rare (3.3%). Eight of nine strains
      resistant to clarithromycin were also resistant to metronidazole. Resistance to
      either metronidazole or clarithromycin was significantly (P=0.022) higher in
      patients with duodenal ulcer. No strain was found to be resistant to amoxicillin
      or tetracycline.

PMID- 9764559
TI  - Comparison of three monoclonal antibody pools for the detection of respiratory
      viral antigen in respiratory secretions.
AB  - The aim of this study was to compare the sensitivities of commercial monoclonal
      antibody pools to be used as an initial rapid screen for detection of viral
      antigens in respiratory secretions. The availability of commercial monoclonal
      antibodies has dramatically improved the detection of viruses by
      immunofluorescence techniques in exfoliated cells obtained from respiratory
      secretions. Several companies have recently introduced monoclonal antibody pools
      to detect the presence of respiratory viruses in a single preparation. Ninety
      four stored slide preparations that had previously been examined by individual
      monoclonal antibodies were tested using three commercial monoclonal antibody
      pools produced by Sanofi (UK), Dako (UK), and Quadratech (UK). These monoclonal
      antibody pools had a sensitivity of 79.6%, 90.9%, and 100%, respectively, when
      compared with the original results. The overall intensity of immunofluorescence
      was also examined.

PMID- 9764560
TI  - Evaluation of restriction fragment length polymorphism analysis of the UL10-UL13
      genomic region for rapid identification of human cytomegalovirus strains.
AB  - A sensitive semi-nested polymerase chain reaction (PCR) was established which
      allows rapid identification of human cytomegalovirus strains directly on clinical
      specimens, thereby permitting virus isolation and propagation on cell cultures to
      be avoided. The assay is based on restriction analysis of PCR products derived
      from the polymorphic UL10-UL13 region of the human cytomegalovirus genome. The
      method was evaluated using clinical samples from 23 subjects comprising 16 breast
      feeding mothers and seven bone marrow transplantation recipients. For eight
      mothers, postnatal virus transmission to their offspring via breast milk was
      studied. Interestingly, for one mother-infant pair, a double infection with two
      distinct human cytomegalovirus strains could be demonstrated. Stepwise digestion
      with different restriction enzymes raised the possibility of detecting different
      strains almost twofold compared to analysis with only one enzyme. This assay is a
      practical tool for monitoring human cytomegalovirus transmission in various
      clinical settings.

PMID- 9764561
TI  - Submandibular gland infection by Mycobacterium avium-intracellulare in an AIDS
      patient.

PMID- 9764562
TI  - Candida and bacterial mandibular osteomyelitis in an AIDS patient.

PMID- 9764563
TI  - Evaluation of an indirect immunofluorescence assay and two cell lines in the
      detection of influenza B virus in nasopharyngeal samples.

PMID- 9764564
TI  - Porphyria cutanea tarda and hepatitis G and C virus infection.

PMID- 9764565
TI  - Comparison of the effectiveness of 2,3-dimercaptopropanol (BAL) and meso-2,3
      dimercaptosuccinic acid (DMSA) as protective agents against mercuric chloride
      induced nephrotoxicity in rats.
AB  - The effectiveness of 2,3-dimercaptopropanol (BAL) and meso-2,3-dimercaptosuccinic
      acid (DMSA) on HgCl2-induced nephrotoxicity was studied in the rat. Seven groups
      of adult male rats were given a single sc toxic dose of HgCl2 (0.68 mg/kg)
      followed by 0.9% saline (positive control group), BAL (15, 30, and 60 mg/kg) or
      DMSA (50, 100, and 200 mg/kg) administered ip at 0, 24, 48, and 72 h thereafter.
      Although the renal function of HgCl2-exposed rats was slightly improved after BAL
      administration, Hg concentrations in the kidney were only reduced at 60 mg/kg. In
      addition, the protective effect of BAL was not dose-related. In contrast to BAL,
      DMSA was effective in increasing the urinary excretion of Hg and in reducing the
      renal Hg content. These results show that DMSA would be more effective than BAL
      in preventing or in protecting against inorganic Hg-induced nephrotoxicity.

PMID- 9764566
TI  - Structural and trace element changes in scalp hair of radiographers.
AB  - Scalp hair samples were collected from medical radiographers and nonradiographers
      of matching age groups. Structural morphology of hair was studied by scanning
      electron microscopy, and the trace element profiles in hair were measured using
      neutron activation analysis. The structural damage to the hair follicles of the
      radiographers was quite obvious, and this may be a good qualitative indicator of
      radiation damage at low doses. The concentrations of aluminum (Al), potassium
      (K), and vanadium (V) in hair of the radiographers were significantly higher,
      whereas those of antimony (Sb) and magnesium (Mg) were significantly lower than
      those of nonradiographers. Some of our findings were quite consistent with those
      of others in determining the changes in trace element concentrations in
      irradiated tissue.

PMID- 9764567
TI  - Pattern of cardiac fibrosis in rabbits periodically fed a magnesium-restricted
      diet and administered rare earth chloride through drinking water.
AB  - It has been postulated that causation of the tropical cardiomyopathy
      endomyocardial fibrosis (EMF) is linked to magnesium (Mg) deficiency and cardiac
      toxicity of the rare earth element cerium (Ce). The aim of the present study was
      to define the myocardial lesions in rabbits that were fed on Mg-restricted diet
      (70-80 ppm) periodically and were provided drinking water contaminated with rare
      earth chloride (1 g/L). Forty New Zealand white rabbits were divided into four
      groups following a 2 x 2 factorial design. Two groups were periodically fed on Mg
      restricted diet with one of them receiving water contaminated with rare earth
      chloride. The other two groups were continuously fed on Mg-sufficient diet (350
      400 ppm) with one of them receiving water contaminated with rare earth chloride.
      All animals were sacrificed at the end of 6 mo. Cardiac tissues were subjected to
      histology, elemental analysis (calcium [Ca], Mg, and Ce) and estimation of
      collagen content and collagen phenotypes. Histological lesions were compared with
      those of EMF in humans and those of acute Mg deficiency in animals. The results
      suggest that in rabbits, recurrent episodes of Mg deficiency lead to myocardial
      fibrosis similar to the pattern observed in human EMF.

PMID- 9764568
TI  - Influence of ascorbic acid, sodium citrate, and sodium bicarbonate on the uptake
      of 59Fe-transferrin, 54Mn-transferrin, and 65Zn-transferrin from lactating mouse
      mammary gland cells.
AB  - The effects of ascorbic acid, sodium citrate, and sodium bicarbonate on 59Fe
      transferrin, 54Mn-transferrin, and 65Zn-transferrin uptake by the receptors
      disposed of plasma membrane isolated from lactating mouse mammary gland cells
      have been investigated. The effect of 10(-2) mol/L ascorbic acid alone and in
      combination with NaHCO3 on the 59Fe-transferrin uptake is significant and
      positive. 54Mn-transferrin and 65Zn-transferrin binding to the cell receptors are
      influenced optimally by 0.5 mol/L sodium bicarbonate. Sodium citrate alone or in
      combination with other substances always has a negative effect on binding of
      these three metals. It is suggested that a precise mechanism may exist with large
      possibilities to rearrange metal uptake and its transport from blood to milk.

PMID- 9764569
TI  - Significance of magnetic resonance image and blood manganese measurement for the
      assessment of brain manganese during total parenteral nutrition in rats.
AB  - In this study, we report on the influence of trace elements (TE) on signal
      intensities of nuclear magnetic resonance images (MRI), both in vivo and in
      vitro. Optimal parameters for the assessment of Mn concentration in the brain of
      rats on total parenteral nutrition were established. For the in vitro study, Mn
      and trace element solutions, one containing Zn, Cu, Fe, and I (TE-4) and another
      containing the above elements plus Mn (TE-5), were diluted with physiological
      saline or with rat brain homogenate and used to measure signal intensities in
      MRI. Concentration-dependent signal hyperintensity was observed in both cases in
      the Mn and the TE-5 solutions, but no effect was observed with the TE-4 solution.
      The signal increase was greater for brain tissue homogenates. In the in vivo
      study, the experimental animals were maintained under total parenteral nutrition
      (TPN) with a standard clinical dose of TE-5 and/or with 10-fold the clinical dose
      of TE-4 and TE-5 for 1 wk. Only rats that were receiving the increased TE-5 dose
      showed signal hyperintensity on MRI. Positive correlations were observed among
      the signal hyperintensity, the blood Mn concentrations, and that of the rat
      brain. Our results suggest that Mn in TE preparations may be the cause of signal
      hyperintensity on MRI in a concentration-dependent fashion, and that MRI and
      measurement of blood Mn may be used to estimate Mn accumulation in brain tissue.

PMID- 9764570
TI  - Effects of selenium supplementation on virus-induced inflammatory heart disease.
AB  - The effects of 10 wk of selenium (Se) supplementation (5 ppm) in drinking water
      on immune responses and resistance to a myocarditic Coxsackie virus B3 (CB3)
      infection were studied in female Balb/c mice. Se supplementation reduced CB3
      induced mortality: at day 14 postinoculation, survival was 58% in the Se-treated
      group as compared to 25% in the untreated group. Whole-blood glutathione
      peroxidase (GSH-Px) activity was elevated by 68% (p < 0.001) and Se content in
      the liver by 24% (p < 0.001). Red (RBC) and white blood cell (WBC) counts, as
      well as the number of cells in the spleen and thymus, were unaffected. The
      cellular counts of T-lymphocytes (CD4+, CD8+) and natural killer (NK+) cells in
      the blood were not affected. However, the CD4+/CD8+ ratio (5.2) tended to
      increase after Se supplementation (5.9). The spleen lymphoproliferative response
      to T- and B-cell mitogens were increased by 9 and 43%, respectively (ns), in the
      Se-supplemented group. The total NK cell activity in blood and spleen showed
      minor increases, but when the activity in the blood was expressed per cell, the
      increase amounted to 35% (ns) with Se supplementation. The inflammatory and
      necrotic lesions in the ventricular myocardium at 7 and 14 d postinoculation were
      not significantly reduced by Se treatment, probably owing to the increased
      survival with Se even of mice with the most pronounced heart damage; comparable
      untreated mice were estimated to have died at day 14. Results indicate that
      modest doses of Se can improve immune function, which may increase the general
      resistance to this viral infection.

PMID- 9764571
TI  - Serum and urine ionic fluoride: normal range in a nonexposed population.
AB  - The present study was undertaken to evaluate the fluoride status in the general
      healthy population of Barcelona. Serum and urine fluoride ionic concentration was
      determined in a random sample of 250 subjects (age range 15-90 yr) by the Orion
      fluoride electrode system to determine the normal range of fluoride in this
      population. The results obtained show that in the general population of
      Barcelona, fluoride ionic serum concentration ranges between 1 and 47 microg/L (x
      = 17.5 +/- 9.7 microg/L) and fluoride ionic urine concentration ranges between
      156 and 1990 microg/24 h (x = 671 +/- 373 microg/24 h). The mean serum fluoride
      concentration of the younger population was shown to be significantly greater (p
      < 0.05) than that of the older group. No sex-related difference was found.

PMID- 9764572
TI  - Alterations in collagen metabolism and increased fibroproliferation in the heart
      in cerium-treated rats: implications for the pathogenesis of endomyocardial
      fibrosis.
AB  - Cerium (Ce), a rare earth element, has been postulated to play a role in the
      pathogenesis of tropical endomyocardial fibrosis (EMF). Investigations carried
      out recently in pursuance of the postulation furnished histological evidence of
      EMF and increased cardiac collagen content in rats on prolonged administration of
      Ce. The present study was undertaken to understand the molecular basis of
      myocardial injury and fibrosis produced by the element. This article presents
      evidence of increased lipid peroxidation and elevated rates of fibroblast
      proliferation and collagen deposition in the heart in Ce-treated rats. It is
      suggested that the element may trigger a wound-healing response in the cardiac
      tissue leading to cardiac fibrosis.

PMID- 9764573
TI  - Role of nitric oxide in pancreatic tumour growth: in vivo and in vitro studies.
AB  - Nitric oxide (NO), an endogenous free radical, has been implicated in a wide
      range of biological functions. NO is generated enzymatically from the terminal
      guanidinonitrogen of L-arginine by nitric oxide synthase (NOS). Despite intensive
      investigations, the role of NO--either as the primary product of the L
      arginine/NOS pathway or provided from the NO donor sodium nitroprusside (SNP)--in
      carcinogenesis and tumour cell growth remains unclear and controversial. The
      objective of this study was to examine the growth effects of NO on a ductal
      pancreatic adenocarcinoma in the rat and on a human pancreatic tumour cell line
      (HA-hpc2). In vivo, both SNP and endogenous induction of NO by endotoxins
      [lipopolysaccharide (LPS)] plus L-arginine significantly reduced the tumour
      growth. To investigate the mechanisms of NO anti-tumour growth action, the
      effects of either the SNP or L-arginine/NOS pathway were analysed on the HA-hpc2
      cell line. Nitrite/nitrate production, NOS activity and iNOS expression [assessed
      by reverse transcription-polymerase chain reaction (RT-PCR)] were tested and
      related to growth (assessed by [3H]thymidine incorporation assay) and apoptosis
      (assessed by internucleosomal DNA cleavage). SNP exerted a dual effect on tumour
      cells: stimulation of the proliferation up to 1 mM and inhibition at higher
      concentrations. These effects were related to NO production. Both proliferative
      and cytostatic responses were inhibited by NO scavenger 2-phenyl-4,4,5,5
      tetramethyl-hemidazoline-1-oxyl3-oxide (carboxy-PTIO). The marked apoptotic DNA
      fragmentation induced by SNP was also abolished by PTIO association. Unlike
      macrophages, the human pancreatic tumour cells did not seem to express
      intrinsically the L-arginine/NOS pathway. Macrophages were activated by HA-hpc2
      cells as well as by LPS plus cytokines [interleukin (IL)-1beta plus tumour
      necrosis factor (TNF)-alpha and interferon (IFN)-gamma]. In HA-hpc2/macrophage co
      cultures, NOS activity and inducible NOS (iNOS) transcription were stimulated,
      whereas an antiproliferative response was observed. These effects were related to
      both macrophage amount and NO production. Addition of LPS plus cytokines to co
      cultures doubled iNOS activity, nitrite/nitrate production and tumoricidal
      effect. These data suggest the involvement of NO in pancreatic tumour growth and
      support the fact that generation of high levels of NO with potential production
      of endogenous reactive nitrogen intermediates may contribute to induction of
      apoptosis and tumour growth inhibition.

PMID- 9764575
TI  - Inhibition by transforming growth factor (34-43)-alpha, a TGF-alpha antagonist,
      of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in
      Wistar rats.
AB  - The effect of prolonged administration of transforming growth factor (34-43)
      alpha, an antagonist of TGF-alpha, on gastric carcinogenesis induced by N-methyl
      N'-nitro-N-nitrosoguanidine (MNNG) and on the labelling and apoptotic indices and
      TGF-alpha immunoreactivity of gastric mucosa and gastric cancers was examined in
      Wistar rats. The rats received intraperitoneal injections of 10 or 20 microg kg(
      1) body weight of TGF(34-43)-alpha every other day after oral treatment with MNNG
      for 25 weeks. Long-term administration of TGF(34-43)-alpha at both doses
      significantly reduced the incidence of gastric cancers at the end of the
      experiment in week 52. However, TGF(34-43)-alpha had no significant effect on the
      number, histological type or depth of involvement of gastric cancers.
      Administration of TGF(34-43)-alpha also significantly decreased the
      bromodeoxyuridine labelling index and TGF-alpha immunoreactivity, and
      significantly increased the apoptotic index of antral mucosa and gastric cancers.
      These findings indicate that TGF(34-43)-alpha inhibits gastric carcinogenesis,
      and that its effects are mediated through decreased cell proliferation and TGF
      alpha immunoreactivity and increased apoptosis induction in the gastric cancers.

PMID- 9764574
TI  - Mechanism of muscle protein degradation induced by a cancer cachectic factor.
AB  - A proteolysis-inducing factor (PIF) isolated from a cachexia-inducing murine
      tumour (MAC16) produced a decrease in body weight (1.6 g, P < or = 0.01 compared
      with control subjects) within 24 h after i.v. administration to non-tumour
      bearing mice. Weight loss was associated with significant decreases in the weight
      of the spleen and soleus and gastrocnemius muscles, with no effect on the weight
      of the heart or kidney and with an increase in weight of the liver. Protein
      degradation in isolated soleus muscle was significantly increased in mice bearing
      the MAC16 tumour. To define which proteolytic pathways contribute to this
      increase, soleus muscles from mice bearing the MAC16 tumour and non-tumour
      bearing animals administered PIF were incubated under conditions that modify
      different proteolytic systems. In mice bearing the MAC16 tumour, there were
      increases in both cathepsin B and L, and the Ca2+-dependent lysosomal and ATP
      dependent pathways were found to contribute to the increased proteolysis;
      whereas, in PIF-injected animals, there was activation only of the ATP-dependent
      pathway. Further studies in mice bearing the MAC16 tumour have provided evidence
      for increased levels of ubiquitin-conjugated proteins and increased mRNA levels
      for the 14 kDa ubiquitin carrier protein E2 and the C9 proteasome subunit in
      gastrocnemius muscle, suggesting activation of the ATP-ubiquitin-dependent
      proteolytic pathway. A monoclonal antibody to PIF attenuated the enhanced protein
      degradation in soleus muscle from mice bearing the MAC16 tumour, confirming that
      PIF is responsible for the loss of skeletal muscle in cachectic mice.

PMID- 9764576
TI  - Autocrine self-elimination of cultured ovarian cancer cells by tumour necrosis
      factor alpha (TNF-alpha).
AB  - Human ovarian adenocarcinoma cells N.1 secrete an autocrine activity that
      stimulates active cell death under serum-reduced conditions. To substitute the
      autocrine activity by a single physiological component, 28 cytokines, growth
      factors and biomodulators were tested [interleukin 1alpha (IL-1alpha), IL-1beta,
      IL-2, IL-3, IL-4, IL-6, IL-10, IL-11, stem cell factor (SCF), platelet-derived
      growth factor (PDGF), acid fibroblast growth factor (aFGF), basic fibroblast
      growth factor (bFGF), insulin-like growth factor (IGF-1), IGF-2, insulin,
      macrophage colony-stimulating factor (M-CSF), granulocyte colony-stimulating
      factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF),
      oncostatin, RANTES (regulated on activation normal T cell expressed and
      secreted), angiogenin, leukaemia inhibitory factor (LIF), erythropoietin (EPO),
      interferon alpha (INF-alpha), INF-gamma, transferrin, tumour necrosis factor
      alpha (TNF-alpha, TNF-beta and bovine serum albumin for control reasons]. In
      these experiments, only TNF-alpha and TNF-beta rapidly induced apoptosis. TNF
      alpha and TNF-receptor 1 were expressed by N.1 cells, and the secretion of TNF
      alpha was verified by enzyme-linked immunosorbent assay (ELISA). Autocrine factor
      triggered apoptosis was inhibited when conditioned supernatant was preincubated
      with anti-TNF-alpha antibody. These findings suggested that the apoptosis
      inducing component of the N.1 autocrine activity was TNF-alpha. In the presence
      of antisense c-myc oligonucleotides, induction of cell death by autocrine factor
      was partly inhibited. Autocrine factor and TNF-alpha stimulated transcription of
      the invasiveness-related protease plasminogen activator/urokinase mRNA (upa) with
      similar kinetics. When N.1 cells were exposed to purified plasminogen
      activator/urokinase protein (uPA), cell matrix contact was disrupted. Thus, uPA
      might serve a physiological role during TNF-induced apoptosis by affecting the
      interactions between cells and the basal membrane, thereby facilitating anoikis.
      This mechanistic study, which was restricted to a single human ovarian carcinoma
      model cell line (N.1), provides evidence that N.1 maintains the capacity to
      undergo c-myc-dependent apoptosis by the TNF-TNF-receptor pathway, and no
      additional pharmacological stimuli for induction of apoptosis are required.

PMID- 9764577
TI  - Tau expression in model adenocarcinomas correlates with docetaxel sensitivity in
      tumour-bearing mice.
AB  - Docetaxel is a new taxoid with clinical activity in breast and lung cancer. Using
      docetaxel-sensitive and -refractory mammary and pancreatic murine tumours, as
      well as human-derived neoplasms, we investigated if a determinant of docetaxel
      sensitivity could be found at the level of its mechanism of action. Because
      microtubules represent the cellular targets of the drug, we studied their
      heterogeneity in the tumour models to try to explain the differences in drug
      sensitivity. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of
      the expression of microtubular components showed that levels of Mbeta4-tubulin
      and Tau mRNAs were higher in the murine sensitive neoplasms than in the
      refractory ones. It was also found that Tau protein levels differed markedly
      among the tumours. In the human-derived sensitive neoplasm, beta-tubulins and
      some Tau isoforms were found to be more abundant than in the resistant one.
      Western blot analysis of MAP2 revealed the presence of several immunoreactive
      species. Some of these polypeptides were also found in higher amounts in the
      docetaxel-sensitive tumours. The possible meaning of these correlations is
      discussed in connection with the regulation of microtubule dynamics.

PMID- 9764578
TI  - Establishment of a retinoic acid-resistant human acute promyelocytic leukaemia
      (APL) model in human granulocyte-macrophage colony-stimulating factor (hGM-CSF)
      transgenic severe combined immunodeficiency (SCID) mice.
AB  - To understand the mechanisms and identify novel approaches to overcoming retinoic
      acid (RA) resistance in acute promyelocytic leukaemia (APL), we established the
      first human RA-resistant APL model in severe combined immunodeficiency (SCID)
      mice. UF-1 cells, an RA-resistant APL cell line established in our laboratory,
      were transplanted into human granulocyte-macrophage colony-stimulating factor (GM
      CSF)-producing SCID (hGMTg SCID) mice and inoculated cells formed subcutaneous
      tumours in all hGMTg SCID mice, but not in the non-transgenic control SCID mice.
      Single-cell suspensions (UF-1/GMTg SCID cells) were similar in morphological,
      immunological, cytogenetic and molecular genetic features to parental UF-1 cells.
      All-trans RA did not change the morphological features of cells or their
      expression of CD11b. RA did not alter the growth curve of cells as determined by
      MTT assay, suggesting that UF-1/GMTg SCID cells are resistant to RA. These
      results demonstrate that this is the first RA-resistant APL animal model that may
      be useful for investigating the biology of this myeloid leukaemia in vivo, as
      well as for evaluating novel therapeutic approaches including patients with RA
      resistant APL.

PMID- 9764579
TI  - Reversal of P-glycoprotein-mediated multidrug resistance by XR9051, a novel
      diketopiperazine derivative.
AB  - XR9051 (N-(4-(2-(6,7-Dimethoxy-1,2,3,4-tetrahydro-2-isoquinolyl)ethyl)phe nyl)-3
      ((3Z,6Z)-6-benzylidene-1-methyl-2,5-dioxo-3-pipera zinylidene) methylbenzamide)
      was identified as a potent modulator of P-glycoprotein-mediated multidrug
      resistance (MDR) following a synthetic chemistry programme based on a natural
      product lead compound. The activity of XR9051 was determined using a panel of
      human and murine drug-resistant cell lines (H69/LX4, 2780AD, EMT6/AR 1.0, MC26
      and P388/DX Johnson). XR9051 was able to reverse resistance to a variety of
      cytotoxic drugs, including doxorubicin, etoposide and vincristine, which are
      associated with classical MDR. At a concentration of 0.3-0.5 microM, XR9051 was
      able to fully sensitize resistant cells to cytotoxics, whereas little or no
      effect was observed on the corresponding parental cell lines. No effect of XR9051
      was observed on the response of cells to non-MDR cytotoxics such as methotrexate
      and 5-fluorouracil. XR9051 was consistently more potent than cyclosporin A (CsA)
      and verapamil (Vpm) in all assays used. XR9051 inhibited the efflux of
      [3H]daunorubicin from preloaded cells and, unlike CsA and Vpm, remained active
      for several hours after removal of resistance-modifying agent. In photoaffinity
      labelling experiments employing [3H]azidopine, XR9051 was able to displace
      binding to P-glycoprotein. In binding studies using [3H]vinblastine, XR9051 was
      shown to be a potent inhibitor of the binding of the cytotoxic to P-glycoprotein
      (EC50 = 1.4 +/- 0.5 nM). Taken together, the results indicate that XR9051
      reverses the MDR phenotype through direct interaction with P-glycoprotein.

PMID- 9764580
TI  - Fraction of radiobiologically hypoxic cells in human melanoma xenografts measured
      by using single-cell survival, tumour growth delay and local tumour control as
      end points.
AB  - Four human melanoma xenograft lines (A-07, D-12, R-18, U-25) grown orthotopically
      in Balb/c nu/nu mice were characterized with respect to the fraction of
      radiobiologically hypoxic cells. The purpose of the study was to establish a firm
      radiobiological basis for future use of the lines in the development and
      evaluation of non-invasive assays of tumour hypoxia. The hypoxic fractions were
      assessed using three different assays, the single cell survival assay, the tumour
      growth delay assay and the local tumour control assay, and the means +/- s.e.
      were found to be 6 +/- 3%, 3 +/- 1% and 5 +/- 2% respectively (A-07), 26 +/- 5%,
      25 +/- 6% and 22 +/- 6% respectively (D-12), 55 +/- 9%, 65 +/- 8% and 48 +/- 7%
      respectively (R-18) and 52 +/- 8%, 59 +/- 7% and 47 +/- 7% respectively (U-25).
      The three assays gave numerical values for the hypoxic fraction that were not
      significantly different for any of the lines. The hypoxic fraction differed
      significantly among the lines; the R-18 and U-25 lines showed higher hypoxic
      fractions than the D-12 line (P < 0.05), which in turn showed a higher hypoxic
      fraction than the A-07 line (P < 0.05), regardless of the assay. The wide range
      of the hypoxic fractions and the significant differences among the lines suggest
      that A-07, D-12. R-18 and U-25 tumours should be useful models in future studies
      attempting to develop non-invasive assays of tumour hypoxia.

PMID- 9764581
TI  - Fatigue and radiotherapy: (A) experience in patients undergoing treatment.
AB  - Cancer patients undergoing radiotherapy frequently report fatigue. However,
      knowledge of the importance of fatigue for these patients and of the factors
      associated with their fatigue is limited. The aim of the current investigation
      was to gain more insight into fatigue as related to radiotherapy by answering the
      following questions. First, how is the experience of fatigue best described?
      Secondly, to what extent is fatigue related to sociodemographic, medical
      (including treatment), physical and psychological factors? Finally, is it
      possible to predict which patients will suffer from fatigue after completion of
      radiotherapy? Patients with different types of cancer receiving radiotherapy with
      curative intent (n = 250) were interviewed before and within 2 weeks of
      completion of radiotherapy. During treatment, patients rated their fatigue at 2
      weekly intervals. Results indicate a gradual increase in fatigue over the period
      of radiotherapy and a decrease after completion of treatment. Fatigue scores
      obtained after radiotherapy were only slightly, although significantly, higher
      than pretreatment scores. After treatment, 46% of the patients reported fatigue
      among the three symptoms that caused them most distress. Significant associations
      were found between post-treatment fatigue and diagnosis, physical distress,
      functional disability, quality of sleep, psychological distress and depression.
      No association was found between fatigue and treatment or personality
      characteristics. Multivariate regression analysis demonstrated that the intensity
      of pretreatment fatigue was the best predictor of fatigue after treatment. In
      view of this finding, a regression analysis was performed to gain more insight
      into the variables predicting pretreatment fatigue. The degree of functional
      disability and impaired quality of sleep were found to explain 38% of the
      variance in fatigue before starting radiotherapy. Fatigue in disease-free
      patients 9 months after treatment is described in paper (B) in this issue.

PMID- 9764582
TI  - Fatigue and radiotherapy: (B) experience in patients 9 months following
      treatment.
AB  - Little is known regarding the prevalence and course of fatigue in cancer patients
      after treatment has ended and no recurrence found. The present study examines
      fatigue in disease-free cancer patients after being treated with radiotherapy (n
      = 154). The following questions are addressed. First, how do patients describe
      their fatigue 9 months after radiotherapy and is this different from fatigue in a
      nonselective sample from the general population (n = 139)? Secondly, to what
      degree is fatigue in patients associated with sociodemographic, medical, physical
      and psychological factors? Finally, is it possible to predict which patients will
      suffer from fatigue 9 months after radiotherapy? Results indicated that fatigue
      in disease-free cancer patients did not differ significantly from fatigue in the
      general population. However, for 34% of the patients, fatigue following treatment
      was worse than anticipated, 39% listed fatigue as one of the three symptoms
      causing them most distress, 26% of patients worried about their fatigue and
      patients' overall quality of life was negatively related to fatigue (r = -0.46).
      Fatigue in disease-free patients was significantly associated with: gender,
      physical distress, pain rating, sleep quality, functional disability,
      psychological distress and depression, but not with medical (diagnosis,
      prognosis, co-morbidity) or treatment-related (target area, total radiation dose,
      fractionation) variables. The degree of fatigue, functional disability and pain
      before radiotherapy were the best predictors of fatigue at 9-month follow-up,
      explaining 30%, 3% and 4% of the variance respectively. These findings are in
      line with the associations found with fatigue during treatment as reported in the
      preceding paper in this issue. The significant associations between fatigue and
      both psychological and physical variables demonstrate the complex aetiology of
      this symptom in patients and point out the necessity of a multidisciplinary
      approach for its treatment.

PMID- 9764583
TI  - High-dose chemotherapy followed by reinfusion of selected CD34+ peripheral blood
      cells in patients with poor-prognosis breast cancer: a randomized multicentre
      study.
AB  - Seventy-one patients with poor-prognosis breast cancer were enrolled after
      informed consent in a multicentre randomized study to evaluate the use of
      selected peripheral blood CD34+ cells to support haematopoietic recovery
      following high-dose chemotherapy. Patients who responded to conventional
      chemotherapy were mobilized with chemotherapy (mainly high-dose cyclophosphamide)
      and/or recombinant human granulocyte colony-stimulating factor (rhG-CSF).
      Patients who reached the threshold of 20 CD34+ cells per microl of peripheral
      blood underwent apheresis and were randomized at that time to receive either
      unmanipulated mobilized blood cells or selected CD34+ cells. For patients in the
      study arm, CD34+ cells were selected from aphereses using the Isolex300 device.
      Fifteen patients failed to mobilize peripheral blood progenitors and nine other
      patients were excluded for various reasons. Forty-seven eligible patients were
      randomized into two comparable groups. CD34+ cells were selected from aphereses
      in the study group. Haematopoietic recovery occurred at similar times in both
      groups. No side-effect related to the infusion of selected cells was observed.
      The frequency of epithelial tumour cells in aphereses was low (8 out of 42
      evaluated patients), as determined by immunocytochemistry. We conclude that
      selected CD34+ cells safely support haematopoietic recovery following high-dose
      chemotherapy in patients with poor-prognosis breast cancer.

PMID- 9764584
TI  - Heterozygosity for mutations in the ataxia telangiectasia gene is not a major
      cause of radiotherapy complications in breast cancer patients.
AB  - Of patients being treated by radiotherapy for cancer, a small proportion develop
      marked long-term radiation damage. It is believed that this is due, at least in
      part, to intrinsic individual differences in radiosensitivity, but the underlying
      mechanism is unknown. Individuals affected by the recessive disease ataxia
      telangiectasia (AT) exhibit extreme sensitivity to ionizing radiation. Cells from
      such individuals are also radiosensitive in in vitro assays, and cells from AT
      heterozygotes are reported to show in vitro radiosensitivity at an intermediate
      level between homozygotes and control subjects. In order to examine the
      possibility that a defect in the ATM gene may account for a proportion of
      radiotherapy complications, 41 breast cancer patients developing marked changes
      in breast appearance after radiotherapy and 39 control subjects who showed no
      clinically detectable reaction after radiotherapy were screened for mutations in
      the ATM gene. One out of 41 cases showing adverse reactions was heterozygous for
      a mutation (insertion A at NT 898) that is predicted to generate a truncated
      protein of 251 amino acids. No truncating mutations were detected in the control
      subjects. On the basis of this result, the estimated percentage (95% confidence
      interval) of AT heterozygous patients in radiosensitive cases was 2.4% (0.1
      12.9%) and in control subjects (0-9.0%). We conclude that ATM gene defects are
      not the major cause of radiotherapy complications in women with breast cancer.

PMID- 9764585
TI  - High-dose etoposide with granulocyte colony-stimulating factor for mobilization
      of peripheral blood progenitor cells: efficacy and toxicity at three dose levels.
AB  - High-dose etoposide (2.0-2.4 g m(-2)) with granulocyte colony-stimulating factor
      (G-CSF) is an effective strategy to mobilize peripheral blood progenitor cells
      (PBPCs), although in some patients this is associated with significant toxicity.
      Sixty-three patients with malignancy were enrolled into this non-randomized
      sequential study. The majority (55/63, 87%) had received at least two prior
      regimens of chemotherapy, and seven patients had previously failed to mobilize
      following high-dose cyclophosphamide with G-CSF. Consecutive patient groups
      received etoposide at three dose levels [2.0 g m(-2) (n = 22), 1.8 g m(-2) (n =
      20) and 1.6 g m(-2) (n = 21)] followed by daily G-CSF. Subsequent leukaphereses
      were assayed for CD34+ cell content, with a target total collection of 2.0 x
      10(6) CD34+ cells kg(-1). Toxicity was assessed by the development of significant
      mucositis, the requirement for parenteral antibiotics or blood component support
      and rehospitalization incidence. Ten patients (16%) had less than the minimum
      target yield collected. Median collections in the three groups were 4.7 (2 g m(
      2)), 5.7 (1.8 g m(-2)) and 6.5 (1.6 g m(-2)) x 10(6) CD34+ cells kg(-1). Five of
      the seven patients who had previously failed cyclophosphamide mobilization
      achieved more than the target yield. Rehospitalization incidence was
      significantly lower in patients receiving 1.6 g m(-2) etoposide than in those
      receiving 2.0 g m(-2) (P = 0.03). These data suggest that high-dose etoposide
      with G-CSF is an efficient mobilization regimen in the majority of heavily
      pretreated patients, including those who have previously failed on high-dose
      cyclophosphamide with G-CSF. An etoposide dose of 1.6 g m(-2) appears to be as
      effective as higher doses but less toxic.

PMID- 9764586
TI  - Telomerase activity and human papillomavirus in malignant, premalignant and
      benign cervical lesions.
AB  - The purpose of this study was to define a correlation between telomerase activity
      and human papillomavirus (HPV) in normal control tissue and in benign,
      premalignant and malignant cervical lesions. Telomerase activity was detectable
      in 33 out of 34 cases of squamous-cell carcinoma, five out of six cases of
      microinvasive carcinoma, 8 out of 20 cases and two out of six cases of high- and
      low-grade squamous intraepithelial lesions (SILs) respectively. The higher
      frequency of positive telomerase in invasive carcinoma compared with SILs was
      observed in both HPV-associated and non-associated groups. Whereas 92.6% of HPV
      positive and 100% of HPV-negative invasive lesions expressed telomerase, only 50%
      of HPV-positive and 25% of HPV-negative SILs did. Interestingly, telomerase
      activity was also detectable in 13 out of 28 cases of benign lesions regardless
      of the presence of HPV. In conclusion, there may be two roles of telomerase in
      the cervix. The first one would present in benign lesions; the second is
      associated with cancer development and activated during the late stage of
      multistep carcinogenesis in both HPV-positive and -negative groups.

PMID- 9764587
TI  - Microvessel density predicts survival in prostate cancer patients subjected to
      watchful waiting.
AB  - The biological potential of prostate cancer is highly variable and cannot be
      satisfactorily predicted by histopathological criteria alone. Angiogenesis, the
      formation of new blood vessels, has been suggested to provide important
      prognostic information in prostate cancer. The aim of this study was to
      investigate whether microvessel density (MVD) at diagnosis was correlated with
      disease-specific survival in a non-curative treated population of prostate cancer
      patients. MVD was immunohistochemically (factor VIII-related antigen) quantified
      in archival tumours obtained at diagnosis in 221 prostate cancer patients. Median
      length of follow-up was 15 years. The maximal MVD was quantified inside a 0.25
      mm2 area of the tumour and the median MVD was 43 (range 16-151) mm2. MVD was
      statistically significantly correlated with clinical stage (P < 0.0001) and
      histopathological grade (P < 0.0001). When dichotomized by the median counts, MVD
      was shown to be significantly associated (P = 0.0001) with disease-specific
      survival in the entire population as well as in the theoretically curable
      clinically localized subpopulation. A multivariate analysis demonstrated that MVD
      was a significant predictor of disease-specific survival in the entire cancer
      population (P = 0.0004), as well as in the clinically localized cancer population
      (P < 0.0001). These findings suggest that quantitation of angiogenesis reflects
      the spontaneous clinical outcome of prostate cancer.

PMID- 9764588
TI  - Epithelial proliferation and hormone receptor status in the normal post
      menopausal breast and the effects of hormone replacement therapy.
AB  - The proliferation rate (as assessed by Ki67 expression) and expression of
      oestrogen-regulated progesterone receptor (PR) was studied in normal post
      menopausal breast epithelium. Normal breast epithelium from patients receiving
      hormone replacement therapy (HRT) at the time of surgery containing either
      oestrogen alone (E2) or oestrogen and progesterone combined activities (E2 + P)
      was also studied, as HRT has been linked to an increased breast cancer risk.
      Samples of breast tissue, containing normal epithelium, from 185 patients
      undergoing surgery for benign or malignant disease were immunocytochemically
      stained for PR and Ki67. The percentage of labelled cells was expressed as the
      labelling index (LI). The median Ki67 LI in normal post-menopausal breast
      epithelium was 0.19 and median PR LI was 4.75, and both were unaffected by
      patient age, duration of menopause or if the tissue sample originated from a
      breast with benign or malignant disease. Proliferation did not alter
      significantly in patients taking HRT (P = 0.61); however, PR expression was up
      regulated in both E2 and E2 + P users (P = 0.01). The dose and duration of HRT
      had no effect on either parameter. A possible attenuation of sensitivity to
      oestradiol-induced proliferation but not to PR expression occurs in the post
      menopausal breast.

PMID- 9764589
TI  - Allelotype analysis of oesophageal adenocarcinoma: loss of heterozygosity occurs
      at multiple sites.
AB  - Deletions of tumour-suppressor genes can be detected by loss of heterozygosity
      (LOH) studies, which were performed on 23 cases of adenocarcinoma of the
      oesophagus, using 120 microsatellite primers covering all non-acrocentric
      autosomal chromosome arms. The chromosomal arms most frequently demonstrating LOH
      were 3p (64% of tumours), 5q (45%), 9p (52%), 11p (61%), 13q (50%), 17p (96%),
      17q (55%) and 18q (70%). LOH on 3p, 9p, 13q, 17p and 18q occurred mainly within
      the loci of the VHL, CDKN2, Rb, TP53 and DCC tumour-suppressor genes
      respectively. LOH on 5q occurred at the sites of the MSH3 mismatch repair gene
      and the APC tumour-suppressor gene. 11p15.5 and 17q25-qter represented areas of
      greatest LOH on chromosomes 11p and 17q, and are putative sites of novel tumour
      suppressor genes. LOH on 9p was significantly associated with LOH on 5q, and
      tumours demonstrating LOH at both the CDKN2 (9p21) and MSH3 (5q11-q12) genes had
      a significantly higher fractional allele loss than those retaining heterozygosity
      at these sites. Six of nine carcinomas displaying microsatellite alterations also
      demonstrated LOH at CDKN2, which may be associated with widespread genomic
      instability. Overall, there are nine sites of LOH associated with oesophageal
      adenocarcinoma.

PMID- 9764590
TI  - The incidence of cancers among second-generation Irish living in England and
      Wales.
AB  - The incidence of ovarian, cervical, lung and prostatic cancer was higher in
      second-generation Irish living in England and Wales than in all other persons in
      England and Wales. A higher incidence of ovarian cancer was not found in first
      generation Irish. Differences in socioeconomic status did not explain these
      patterns.

PMID- 9764591
TI  - Seventeen-year evaluation of breast cancer screening: the DOM project, The
      Netherlands. Diagnostisch Onderzoek (investigation) Mammacarcinoom.
AB  - The DOM project is a non-randomized population-based breast cancer screening
      programme in Utrecht which started in 1974-75. The 17-year effect has been
      evaluated by a case-control study of breast cancer deaths during the period 1975
      92 in women living in the city of Utrecht, born between 1911 and 1925, whose
      breast cancers were diagnosed after the initiation of the DOM project. Controls
      (three for each case) were defined as women having the same year of birth as the
      case, living in the city of Utrecht at the time the case died, and having had the
      opportunity of screening in the DOM project. Screening in the period 1975-92
      indicated a breast cancer mortality reduction of 46% (odds ratio of 0.54, 95%
      confidence interval 0.37-0.79). The strongest protective effect was found at a
      screening interval of 2 years or less (mortality reduction of 62%, odds ratio of
      0.38), and for the highest number of screens (mortality reduction of 68%, odds
      ratio of 0.32 for more than four screens). Exclusion of breast cancer deaths that
      occurred within 1 year of diagnosis, to allow for 'lead-time' bias, gave an odds
      ratio of 0.61. Early diagnosis of breast cancer by screening reduces breast
      cancer mortality in the long term. Bias due to the study design may slightly
      overestimate the protective effect. A screening programme with a 2-yearly, or
      smaller, interval between successive screens will improve the protection of
      screening.

PMID- 9764592
TI  - Risk of cancer other than Kaposi's sarcoma and non-Hodgkin's lymphoma in persons
      with AIDS in Italy. Cancer and AIDS Registry Linkage Study.
AB  - Record linkage was carried out between the national Registry of AIDS and 13
      Cancer Registries (CRs) covering, in 1991, about 15% of the Italian population.
      Observed and expected numbers of cancers and standardized incidence ratios (SIRs)
      were assessed in 6067 persons with AIDS, for a total of 25,759 person-years.
      Significantly increased SIRs were found for Hodgkin's disease [8.9, 95%
      confidence interval (CI) 4.4-16.0], in which seven of 11 cases were of mixed
      cellularity type; invasive carcinoma of the cervix uteri (15.5; 95% CI 4.0-40.1);
      and non-melanomatous skin cancer (3.0, 95% CI 1.3-5.9), in which five of eight
      cases were basal cell carcinoma. An excess was also seen for brain tumours, but
      this may be partly due to misdiagnosis of brain non-Hodgkin's lymphoma or other
      brain diseases occurring near the time of the AIDS diagnosis. The risk for all
      cancer types, after exclusion of Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma
      (NHL), was approximately twice the general population risk. An increased SIR for
      Hodgkin's disease in persons with AIDS is thus confirmed, though it is many times
      smaller than that for NHL. An association with invasive carcinoma of the cervix
      is also shown at a population level. The excess of non-melanomatous skin cancer
      seems to be lower than in transplant recipients.

PMID- 9764593
TI  - Overexpression of p53 in different subtypes of intestinal metaplasia and gastric
      cancer.
AB  - p53 immunostaining was evaluated in cancerous epithelia and adjacent intestinal
      metaplasia of 135 gastric cancer specimens. The differential p53 overexpression
      in different subtypes of intestinal metaplasia and gastric cancer suggests that
      type III intestinal metaplasia is the commonest lesion in dysplasia-carcinoma
      transition, particularly in the intestinal type of gastric cancer.

PMID- 9764594
TI  - Epidemiology of childhood brain tumours in Yorkshire, UK, 1974-95: geographical
      distribution and changing patterns of occurrence.
AB  - From a high-quality population-based register of children with cancer, 455 cases
      diagnosed with central nervous system (CNS) tumours were analysed to examine
      patterns of occurrence and geographical distribution. There was a significant
      increase of 1.8% (95% CI 0.5-3.1, P < 0.01) in average annual incidence for all
      CNS tumours, mainly accounted for by a 3.1% rise (95% CI 0.1-6.1, P < 0.05) in
      primitive neuroectodermal tumours (PNETs) over the 22-year period 1974-95. These
      increases were not explained by an increase in the proportion of histologically
      verified tumours. In the most recent time period (1986-95), astrocytomas occurred
      more commonly than previously in 0 to 4-year olds. Geographical differences in
      incidence were evident at a large scale, between counties, for all tumours and
      astrocytomas, with lower rates in the most urbanized areas. At the level of
      census district and electoral wards, no association between incidence of CNS
      tumours and socioeconomic group, person-based population density or ethnicity was
      observed using Poisson regression modelling. Based on small-scale census
      geography, the patterns of distribution of CNS tumours do not suggest strong
      associations with geographical determinants of risk. This study finds a rising
      incidence of all CNS tumours and particularly primitive neuroectodermal tumours
      and shows that astrocytomas appear to be occurring at a younger age, most
      probably because of improved diagnosis with non-invasive technology.

PMID- 9764595
TI  - Regulation of cytokine expression by an autoreactive B cell clone derived from
      MRL/MP-lpr/lpr mice.
AB  - The B cell line, MRL159.5, was established by somatic hybridization between
      splenic MRL/MP-lpr/lpr (lpr) mice B cells and 2.52M, a hypoxanthine-aminopterine
      thymidine (HAT) medium-sensitive B cell line mutant. It possessed a receptor
      molecule for mouse erythrocytes treated with bromelain (Br-MRBC) on its surface,
      likely to be an autoreactive B cell clone specific for Br-MRBC as detected by
      rosette-forming assay with Br-MRBC. MRL159.5 spontaneously produced IL-6 and
      secreted IgM, and was induced to augment IgM secretion when treated with Br-MRBC
      or IL-6. Triggering of CD40 led to an augmentation of IgM secretion as well as IL
      6 expression. Blocking the binding of IL-6 to its cellular receptor through the
      use of inhibitory antibodies inhibited CD40-induced IgM secretion, suggesting a
      possible autocrine role of IL-6 for CD40-induced differentiation of this B cell
      hybridoma. Addition of IL-4 or Br-MRBC augmented IL-6 expression as well as IgM
      secretion by CD40-activated MRL159.5 cells. CD40 also augmented tumour necrosis
      factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM
      CSF) expression but resulted in decreased IL-10 expression. Furthermore, under
      conditions where IL-6 expression was augmented, IL-6R alpha (gp80) expression was
      down-regulated, suggesting a negative feedback mechanism of an IL-6 autocrine
      loop in this hybridoma. These results demonstrate a role by which T cell
      dependent activation through CD40 regulates an IL-6 autocrine loop, controlling
      differentiation of autoreactive B cells in autoimmune disease.

PMID- 9764596
TI  - Mercury-induced autoimmunity in the absence of IL-4.
AB  - In susceptible H-2S mice, mercuric chloride (HgCl2) induces an autoimmune
      syndrome characterized by production of anti-nucleolar antibodies (ANoA) and
      increased serum levels of IgG1 and IgE antibodies. The increase in serum IgG1 and
      IgE, which are under IL-4 control, suggests a role for the Th2 subset in the
      induction of this syndrome. We have previously shown that administration of IL
      12, a potent Th1-promoting cytokine, resulted in a dramatic reduction of the
      HgCl2-induced anti-nucleolar antibody titres and inhibited serum IgG1 increase.
      These results suggest that Th1 T cells can down-regulate ANoA, and support a role
      for the Th2 subset in ANoA production, possibly via IL-4. To examine the role of
      IL-4 in this syndrome, C57Bl/6 mice (H-2b) with a targeted deletion of the IL-4
      gene were mated with A.SW mice (H-2S) to yield H-2S mice lacking IL-4. We then
      analysed ANoA and serum immunoglobulin levels in these mice after HgCl2
      treatment. While mercury-treated IL-4(-/-) H-2S mice had virtually no detectable
      serum IgG1 or IgE, and very low levels of IgG1 ANoA, these mice had levels of
      IgG2a and IgG2b class ANoA comparable to mercury-treated IL-4+ H-2S mice,
      indicating that IL-4 is not required for the ANoA response in mercury-induced
      autoimmunity.

PMID- 9764597
TI  - Macrophage function in alloxan diabetic mice: expression of adhesion molecules,
      generation of monokines and oxygen and NO radicals.
AB  - The increased incidence of bacterial and mycotic infections in poorly controlled
      diabetic patients or animals is frequently attributed to impaired activities of
      professional phagocytes (granulocytes, macrophages) in hypoinsulinaemic milieu.
      We measured production of monokines (IL-6 and tumour necrosis factor-alpha (TNF
      alpha)), active NO and reactive oxygen intermediates (ROIs), as well as
      expression of several cell surface adhesion molecules (Mac-1, -2 and -3,
      intercellular adhesion molecule-1 (ICAM-1) and Fc gammaRII), by thioglycollate
      medium-induced peritoneal macrophages of normoglycaemic and alloxan diabetic
      CBA/J mice (blood glucose level in the range 300 or 500 mg/dl). Macrophages of
      animals with moderate diabetes (300 mg/dl) produced significantly more IL-6 and
      TNF-alpha and ROIs than cells of control mice and showed an increased expression
      of all cell surface molecules, except Mac-3. NO/NO2 production was not affected.
      Administration of insulin restored enhanced values to normal levels, except for
      the production of ROIs which remained unusually high. We conclude that two
      separate mechanisms influence macrophage physiology in diabetes--lack of
      saturation of insulin receptors on macrophages and an indirect effect due to
      formation of advanced glycosylation endproducts (AGE) on their surfaces. The
      latter is possibly responsible for increased generation of ROIs, since it cannot
      be down-regulated by prolonged insulin treatment. How the increased activity of
      macrophages of moderately diabetic mice (enhanced production of proinflammatory
      monokines and oxygen radicals as well as expression of molecules) is related to
      their ability to kill bacteria is now under investigation.

PMID- 9764598
TI  - Accumulation of immunoglobulin-containing cells in the gut mucosa and presence of
      faecal immunoglobulin in severe combined immunodeficient (scid) mice with T cell
      induced inflammatory bowel disease (IBD).
AB  - Scid mice transplanted either with a gut wall graft or with low numbers of
      purified CD4+ T cells from immunocompetent syngeneic donor mice show clinical
      signs of IBD 3-4 months post-transplantation. The disease is mediated by mucosa
      infiltrating CD4+ TCR alphabeta+ T cells. The pathology of 52 individual colon
      segments obtained from 20 gut wall- or CD4+ T cell-transplanted diseased scid
      mice was evaluated by histology and the numbers of infiltrating immunoglobulin
      containing cells were determined. In particular, cells positive for IgM, IgA and
      non-inflammatory immunoglobulin isotypes such as IgG1 and IgG2b were found to
      accumulate in colon segments displaying the most severe histopathology, including
      inflammatory cellular infiltration, epithelial hyperplasia and ulcerative
      lesions. Compared with colon segments of normal C.B-17 mice, the lesional scid
      colon shows increased levels of cells positive for the IgG classes. Faecal
      extracts of the CD4+ T cell-transplanted scid mice revealed the presence of all
      six murine immunoglobulin isotypes. Disease progression was accompanied by an
      increased level of excreted IgM and IgG3 and decreased levels of IgA. It is
      concluded that locally secreted immunoglobulins may play an immunomodulating role
      in the pathological changes observed in the present model of T cell-induced
      inflammatory bowel disease.

PMID- 9764599
TI  - Perioperative cytokine release during coronary artery bypass grafting in patients
      of different ages.
AB  - Surgical interventions and cardiopulmonary bypass (CPB) induce a systemic
      inflammatory response with cytokine release. Ageing is perceived as a process of
      impaired immune functions: IL-1beta, IL-6 and tumour necrosis factor-alpha (TNF
      alpha) secretion are increased while IL-2 release is reduced in advanced age. At
      present, little information is available about perioperative immune reactions at
      different stages of ageing. The aim of the present study was to compare IL-6, IL
      1beta, TNF-alpha, IL-10 and soluble IL-2 receptor (sIL-2R) in younger and older
      patients undergoing cardiac surgery. Male patients (n = 14) undergoing elective
      coronary artery bypass grafting (CABG) surgery employing CPB with moderate
      hypothermia were divided into two groups according to their age: group 1 included
      seven patients < 50 years old, group 2 included seven patients > 65 years old.
      All patients received general anaesthesia using a balanced technique with
      sufentanil, isoflurane and midazolam. Blood samples were collected pre
      operatively (T1); intra-operatively during CPB (T2); post-operatively on the day
      of surgery (T3); on the first post-operative day (T4). Blood concentrations of IL
      6, IL-1beta, IL-10, TNF-alpha and sIL-2R were measured using commercially
      available ELISA kits and corrected for plasma cell volume. Statistical analysis
      was performed by non-parametric analysis of variance and Mann-Whitney U-test.
      Significance level was set to P<0.05. There were no statistically significant
      differences in the perioperative release of TNF-alpha, IL-6, IL-1beta, IL-10 and
      sIL-2R among the two groups. We conclude that the perioperative course of
      cytokine release in patients undergoing CABG surgery with CPB and comparable
      perioperative management does not significantly differ in the two age groups.

PMID- 9764600
TI  - Somatic mutation of immunoglobulin V(H)6 genes in human infants.
AB  - Infants respond to antigen by making antibody that is generally of low affinity
      for antigen. Somatic hypermutation of immunoglobulin genes, and selection of
      cells expressing mutations with improved affinity for antigen, are the molecular
      and cellular processes underlying the maturation of antibody affinity. We have
      reported previously that neonates and infants up to 2 months of age, including
      individuals undergoing strong immunological challenge, show very few mutated
      V(H)6 sequences, with low mutation frequencies in mutated sequences, and little
      evidence of selection. We have now examined immunoglobulin genes from healthy
      infants between 2 and 10 months old for mutation and evidence of selection. In
      this age group, the proportion of V(H)6 sequences which are mutated and the
      mutation frequency in mutated sequences increase with age. There is evidence of
      selection from 6 months old. These results indicate that the process of affinity
      maturation, which depends on cognate T-B cell interaction and functional germinal
      centres, is approaching maturity from 6 months old.

PMID- 9764601
TI  - Evidence of idiotypic modulation in the immune response to gp43, the major
      antigenic component of Paracoccidioides brasiliensis in both mice and humans.
AB  - Paracoccidioidomycosis (PCM) is a systemic mycosis endemic in Latin America, with
      a high prevalence in Brazil, Argentina, Colombia and Venezuela. The aetiologic
      agent of disease is a thermal dimorphic fungus, Paracoccidioides brasiliensis. A
      glycoprotein of 43,000 D (gp43) is the major antigen of P. brasiliensis.
      Antibodies directed to this antigen are detected in the sera of all patients with
      PCM. Gp43 binds to laminin, thus participating in adhesion, invasion and
      pathogenesis of the fungus. As the role of antibodies in PCM is not fully
      understood, we decided to investigate the outcome of mice immunization with three
      distinct anti-gp43 MoAbs (17c, 8a and 24a) coupled with keyhole limpet
      haemocyanin (KLH). Results show not only the expected presence of anti-Id (AB2)
      antibodies in the sera of these animals but also a spontaneous and increasing
      amount of anti-anti-Id (AB3) antibodies after the third course of immunization.
      Hybridomas producing both AB2 and AB3 MoAbs were obtained using spleen cells from
      mice immunized with MoAb 17c. AB3 MoAbs were also obtained with spleen cells of
      mice immunized with MoAbs 8a and 24a. It was also shown that human PCM patients'
      sera with high titres of anti-gp43 antibodies generate anti-Id antibodies. These
      data suggest that the immune response to P. brasiliensis can be spontaneously
      modulated by the idiotypic network.

PMID- 9764602
TI  - The apoptosis of neutrophils is accelerated in respiratory syncytial virus (RSV)
      induced bronchiolitis.
AB  - Neutrophils are the predominant inflammatory cell in the lung tissues and airways
      in RSV infection, and can augment the epithelial cell damage induced by RSV.
      Neutrophil apoptosis has been suggested to be a mechanism to reduce the potential
      for tissue injury. The apoptosis of neutrophils from nasopharyngeal aspirates
      (NPA) (n = 19) and peripheral blood (PB) of infants with RSV bronchiolitis (n =
      11) and PB from healthy controls (n = 9) was investigated. Monoclonal antibody
      against CD95 (Fas) and a binding protein Annexin V were used to determine the
      apoptosis of neutrophils. The expression of CD11b and CD18 on neutrophils was
      also detected with flow cytometry. The mean fluorescence intensity (MFI) of CD95
      on neutrophils from RSV+ NPA was increased compared with cells from control PB
      (73.6 +/- 7.6 versus 31.5 +/- 4.3); the MFI of Annexin V, CD11b and CD18 on
      neutrophils from RSV+ NPA was up-regulated compared with cells from both control
      PB (105.3 +/- 18.1 versus 11.8 +/- 1.5; 1683 +/- 153.3 versus 841.1 +/- 72.3; 517
      +/- 50.5 versus 147 +/- 8.7, respectively) and RSV+ PB (105.3 +/- 18.1 versus
      35.8 +/- 4.1; 1683 +/- 153.3 versus 818 +/- 141.2; 517 +/- 50.5 versus 260 +/-
      25.8, respectively). Furthermore, the percentage of neutrophils expressing
      Annexin V and the MFI of CD18 on neutrophils from RSV+ PB were increased compared
      with neutrophils from control PB. In addition, both CD11b (MFI) and CD18 (MFI)
      correlated with Annexin V (MFI) on neutrophils. We conclude that neutrophil
      apoptosis in RSV bronchiolitis is accelerated; and CD11b/CD18 may play an
      important role in RSV infection by influencing neutrophil apoptosis.

PMID- 9764603
TI  - mRNA cytokine profile in peripheral blood cells from chronic hepatitis C virus
      (HCV)-infected patients: effects of interferon-alpha (IFN-alpha) treatment.
AB  - Natural immune responses, both cellular and humoral, are not capable of
      terminating HCV infection in most patients. A role has been suggested for
      peripheral blood leucocytes (PBL) in viral persistence and clinical implications,
      as these cells may serve as a viral reservoir and at the same time may be
      inadequate active participants in antiviral immune reactions. IFN-alpha
      administration, although only partially successful, is currently the main therapy
      available for chronic HCV patients. In addition to its antiviral effects, IFN
      alpha regulates the function of cytokines, their receptors and other molecules of
      immune importance. The aim of this study was to determine cytokine mRNA
      expression in PBL derived from chronic HCV patients prior to and at termination
      of IFN-alpha treatment. HCV RNA was still observed in sera of most patients (10
      out of 14 treated patients) at termination of treatment. In pretreated patients
      mRNA expression of Th2 (IL-4, IL-6 and IL-10) and Th3 (transforming growth factor
      beta (TGF-beta)) was observed in only a low percentage of PBL samples from
      patients, similar to controls. IFN-alpha treatment led to an elevation in the
      number of samples expressing these cytokines (significant for IL-4, IL-6, IL-10,
      tumour necrosis factor-alpha (TNF-alpha) and TGF-beta), accompanied by reduction
      in liver enzymes but in serum viral load in only approximately 30% of patients.
      Expression of TNF-alpha and TNF-beta mRNA was observed in samples from patients
      but not controls, while no differences were observed for mRNA of classical Th1
      cytokines (IL-2 and IFN-gamma) between patients before or during treatment as
      well as controls. The cytokine mRNA profile following IFN-alpha treatment points
      to an anti-inflammatory response which does not appear to be involved in
      termination of the viral infection. The PBL cytokine profile observed in this
      study may explain the failure of the immune system to eradicate HCV chronic
      infection and suggests that early treatment in the acute phase of disease with
      agents that stimulate cytotoxic immune type 1 responses may lead to eradication
      of HCV infection.

PMID- 9764604
TI  - Tumour necrosis factor (TNF) and TNF-related molecules in HIV-1+ individuals:
      relationship with in vitro Th1/Th2-type response.
AB  - We examined the secretion and expression by peripheral blood mononuclear cells
      (PBMC) of TNF-alpha and TNF-related molecules with regard to Th1/Th2-type
      cytokine production. In 76 HIV+ patients at different disease stages and in 25
      controls we measured cytokine (TNF-alpha/beta, interferon-gamma (IFN-gamma), IL
      2, IL-4, IL-10), and activation marker secretion (sCD4, sCD8, sCD30) in
      phytohaemagglutinin (PHA)-stimulated and unstimulated PBMC cultures by ELISA, and
      membrane-bound TNF-alpha and CD30 expression by flow cytometry. We found an
      expansion of the TNF system in HIV+ individuals, that positively correlated with
      TNF-alpha, IFN-gamma and sCD8, probably representing activation of the cytotoxic
      compartment. In advanced disease these correlations disappeared, and TNF-alpha
      and TNF-related molecules positively correlated with IL-10. Our results are in
      line with the hypothesis that an expanded TNF system is immunopathological in
      conjunction with Th2-type immunity in the advanced stage of disease and with the
      inexorable progression to disease seen when both IL-10 and TNF-alpha are
      elevated.

PMID- 9764605
TI  - Expression of the activation antigen CD69 predicts functionality of in vitro
      expanded peripheral blood mononuclear cells (PBMC) from healthy donors and HIV
      infected patients.
AB  - Gene therapy for AIDS necessitates harvest and expansion of PBMC from HIV
      infected patients. We expanded PBMC from healthy blood donors and HIV-infected
      patients for up to 14 days using four expansion protocols: 3 days of
      phytohaemagglutinin (PHA) stimulation, continuous PHA stimulation, 3 days of
      stimulation with anti-CD3 and anti-CD28, and continuous stimulation with anti-CD3
      and anti-CD28. Functionality of PBMC was evaluated prior to and after expansion
      using standard proliferation assay. Phenotype and lymphocyte subset activation
      defined by expression of CD69 and CD25 were determined using flow cytometry. PBMC
      from healthy donors and HIV-infected patients were readily expanded. The best
      expansion was obtained using stimulation for 3 days. After expansion,
      functionality of PBMC measured as proliferative response was partly conserved.
      PBMC expanded with stimulation for 3 days exhibited more preserved functionality
      than PBMC stimulated continuously (P < 0.03). The mean proliferative response in
      each of the four different expansion protocols correlated with the mean values of
      CD69 expression. The proliferative responses from patients and healthy donors
      expanded with PHA stimulation for 3 days correlated with CD69 expression on CD4
      cells (r = 0.68, P < 0.01) and on CD8 cells (r = 0.59, P < 0.03). Furthermore,
      expression of CD69 reliably predicted which patients and donors had highly
      conserved functionality after in vitro expansion. Finally, PBMC expanded with PHA
      stimulation for 3 days were examined for apoptosis. Only a minor fraction was
      primed for apoptosis, and this fraction could be significantly reduced by
      addition of IL-2 to the culture medium (P < 0.05). In conclusion, the feasibility
      of expanding PBMC from HIV patients was demonstrated. Expanded PBMC had conserved
      functionality. Finally, after in vitro expansion, expression of the activation
      antigen CD69 reliably predicted functionality of PBMC.

PMID- 9764606
TI  - Neutrophil adhesion molecules in HIV disease.
AB  - Neutrophil dysfunction in HIV disease is well described. We examined the
      expression of neutrophil adhesion molecules amongst 72 HIV-infected subjects
      using a whole blood flow cytometric assay with FITC- and R-PE-labelled isotype
      specific MoAbs. We report lesser expression of CD11a (LFA-1) and L-selectin
      (CD62L) on the circulating neutrophils of HIV+ subjects compared with HIV-
      controls. Expression of CD11b (Mac-1) was unchanged. Shedding of L-selectin and
      up-regulation of CD11b in response to in vitro stimulation with N-formyl
      methionyl-leucyl-phenylalanine (fMLP) were less in HIV+ compared with HIV-
      subjects, most markedly in subjects with CD4 cell counts < 100 cells/mm3. These
      results suggest that neutrophil dysfunction in HIV disease, which increases with
      disease progression, may be attributable to dysregulated adhesion molecule
      expression.

PMID- 9764607
TI  - Differential production of IL-10 by T cells and monocytes of HIV-infected
      individuals: association of IL-10 production with CD28-mediated immune
      responsiveness.
AB  - Immune unresponsiveness in HIV-1 infection can result from impaired signals
      delivered by the costimulatory CD28-B7 pathway and the altered production of
      immunoregulatory cytokines, in particular IL-10, whose production is altered in
      HIV-1 infection. In this study we investigate IL-10 regulation in T cells and
      monocytes from HIV+ individuals, and its association with CD28-mediated T cell
      proliferation. IL-10 production as analysed in T cell- and monocyte-depleted
      peripheral blood mononuclear cells (PBMC), and by intracellular staining at the
      single-cell level, reveals a defect in IL-10 production by CD4+ and CD8+ T cells,
      whereas monocytes constitute the major IL-10-producing cell type. To investigate
      the impact of IL-10 on immune responsiveness, CD28-mediated proliferative
      responses in HIV+ individuals were correlated with PHA-induced IL-10 production.
      CD4+ T cells expressed CD28, yet exhibited markedly reduced CD28-mediated cell
      proliferation. This CD28-mediated CD4+ T cell proliferation was found to be
      inversely associated with the levels of PHA-induced IL-10 production and could be
      restored, at least in part, by anti-IL-10 antibodies. These results suggest that
      IL-10 production is differentially regulated in T cells and monocytes of HIV+
      individuals, and that IL-10 may have a role in inducing immune unresponsiveness
      by modulating the CD28-B7 pathway.

PMID- 9764608
TI  - Enhancement of HIV-1 replication in human macrophages is induced by CD8+ T cell
      soluble factors.
AB  - We previously reported that CD8+ T cell-derived factors enhanced HIV long
      terminal repeat (LTR)-mediated gene expression and replication in monocytic cell
      lines. We now report that replication of NSI and SI primary isolates of HIV-1 in
      human macrophages were significantly enhanced by CD8+ T cell supernatants. The
      CD8-mediated enhancement of HIV replication was abrogated by pertussis toxin in a
      dose-dependent manner. The sensitivity to pertussis toxin suggests that the CD8+
      T cell-derived enhancing factor is acting through a G protein-coupled signalling
      pathway. Enhanced HIV replication in macrophages was accompanied by increased
      levels of HIV-1 mRNA, suggesting that CD8 enhancement was mediated at the
      transcriptional level. Interestingly, the replication of HIV(Bal), which
      replicates to high levels in macrophages, was not significantly modulated by
      culture with CD8+ T cell supernatants. Although direct co-culture of activated
      CD8+ T cells with HIV(Ada)-infected macrophages did not modulate replication,
      separation of the CD8+ T cells from macrophages in transwell cultures resulted in
      significant enhancement of replication. The inability to detect a modulatory
      effect in direct co-cultures appeared to be due to non-specific lysis of infected
      macrophages. Thus, soluble factors produced by CD8+ T cells exert strong
      enhancing effects on HIV-1 replication in human macrophages.

PMID- 9764609
TI  - Increased nitric oxide (NO) production by antigen-presenting dendritic cells is
      responsible for low allogeneic mixed leucocyte reaction (MLR) in primary biliary
      cirrhosis (PBC).
AB  - The levels of blastogenesis in allogeneic MLR containing T cells from one normal
      volunteer and irradiated dendritic cells from 29 patients with PBC, 17 patients
      with chronic hepatitis type C (CH-C) and 22 allogeneic normal controls were
      compared to see if there is any role of antigen-presenting cells (APC) in the
      pathogenesis of PBC. The stimulatory capacity of dendritic cells from PBC was
      significantly lower compared with that of dendritic cells from CH-C (P < 0.05)
      and normal controls (P < 0.05), which could not be attributable either to the
      levels of expression of surface molecules, such as HLA-DR and CD86 on dendritic
      cells, or to the levels of cytokines, such as IL-10 and IL-12. Significantly
      higher levels of NO were seen in the allogeneic MLR supernatants containing
      dendritic cells from PBC compared with the supernatants from cultures containing
      dendritic cells from CH-C (P < 0.001) or normal controls (P < 0.001). Moreover,
      dendritic cells from PBC produced 10 times more NO compared with dendritic cells
      from CH-C and normal controls (21.9 +/- 2.8 microM versus 1.6 +/- 0.3 microM and
      1.6 +/- 0.3 microM, respectively; P < 0.001). The addition of N(G)-monomethyl-L
      arginine monoacetate (L-NMMA), a known inhibitor of NO in allogeneic MLR
      containing dendritic cells from PBC, resulted in a significant decrease of NO and
      increase of blastogenesis. The selective impairment of dendritic cell function,
      increased production of NO by dendritic cells and restoration of blastogenesis
      using NO inhibitor in PBC have suggested a role for NO and dysfunction of
      dendritic cells in the pathogenesis of PBC. This inspires optimism that
      modulating the function of dendritic cells and controlling NO production, an
      improved therapeutic approach, might be planned for PBC.

PMID- 9764610
TI  - Soluble complement receptor type 1 (sCR1) in chronic liver diseases: serum levels
      at different stages of liver diseases.
AB  - Complement receptor type 1 (CR1) is an integral membrane protein of many
      haematopoietic cells and plays an important role in the clearance of complement
      associated immune complexes, favouring their transport to liver and spleen
      macrophages. A small amount of soluble CR1 (sCR1) is also found in plasma and
      might originate directly from release of leucocytes and other circulating cells.
      In previous studies, an increase in serum sCR1 level has been observed in liver
      cirrhosis and end-stage renal failure. High levels have also been found in
      patients with some haematologic malignancies. sCR1 serum levels were measured
      using a specific double sandwich ELISA assay. The present study demonstrates the
      correlation between mean serum sCR1 concentrations and disease severity in
      patients with chronic liver disease. In patients with liver cirrhosis, grouped
      according to the Child-Pugh classification, sCR1 rose as liver function
      decreased. The presence of neoplastic growth in the liver apparently does not
      play a role in the increase of sCR1. Serum sCR1 was not elevated in other solid
      malignancies. Since sCR1 accumulates in liver diseases, evaluation of its serum
      levels could be useful as a liver function test.

PMID- 9764611
TI  - Apoptosis in labial salivary glands from Sjogren's syndrome (SS) patients:
      comparison with human T lymphotropic virus-I (HTLV-I)-seronegative and 
      seropositive SS patients.
AB  - Apoptosis is a type of cell death that occurs during morphogenesis and
      development of the immune system. One of the mechanisms is mediated through the
      Fas and Fas ligand (FasL) pathway. To determine the possible involvement of Fas
      and its ligand in salivary gland destruction, we analysed the appearance of
      nuclei with DNA fragmentation by using nick end labelling (TUNEL) and the
      expression of Fas and FasL by immunohistochemistry in labial salivary glands.
      Furthermore, we compared the features of apoptosis in labial salivary glands
      between HTLV-I- and HTLV-I+ SS. When the frozen sections of 10 primary SS
      patients in the absence of anti-HTLV-I antibody were examined, several apoptotic
      cells were found in the acinar and ductal epithelial cells as well as infiltrated
      mononuclear cells. Both Fas and FasL were detected in the infiltrated mononuclear
      cells. Acinar epithelial cells, which are surrounded by FasL+ mononuclear cells,
      were also double-positive with Fas and FasL, although the expression of FasL was
      localized at their apical border, suggesting that apoptosis of mononuclear cells
      was achieved by activation-induced mechanisms through Fas/FasL pathways, and that
      of acinar epithelial cells was mediated by FasL derived from either acinar
      epithelial cells themselves or infiltrated mononuclear cells. Interestingly, Fas
      expression in ductal epithelial cells was localized around the lumen side of the
      ducts, indicating that FasL secreted from acinar epithelial cells may induce Fas
      mediated apoptosis of ductal epithelial cells. We also studied the labial
      salivary glands from nine SS patients with anti-HTLV-I antibodies. There was no
      significant difference in the occurrence of apoptotic cells or in the expression
      of Fas and FasL between HTLV-I+ and HTLV-I- SS patients. It was of note that
      neither the expression of Fas and FasL nor the presence of apoptotic cells were
      determined in labial salivary glands from subjects without SS. These findings
      indicate that Fas-mediated apoptosis in salivary glands could be involved in the
      pathological manifestations of SS, irrespective of HTLV-I seropositivity.

PMID- 9764612
TI  - Costimulatory molecules in Wegener's granulomatosis (WG): lack of expression of
      CD28 and preferential up-regulation of its ligands B7-1 (CD80) and B7-2 (CD86) on
      T cells.
AB  - T cells are most likely to play an important role in the pathogenesis of WG, and
      recently a predominant Th1 pattern of immune response has been demonstrated in
      granulomatous inflammation. Since the expression of costimulatory molecules has a
      significant impact on the cytokine profile and proliferation response of T cells,
      the goal of this study was to characterize the expression of costimulatory
      molecules (CD28, CTLA-4 (CD152), B7-1 (CD80), B7-2 (CD86)) on T cells, monocytes
      and B cells in WG, and to correlate the findings with clinical parameters such as
      disease activity, extent and therapy. WG patients (n = 24) and healthy controls
      (HC; n = 17) were examined for the expression of costimulatory molecules by
      fluorescence-activated cell sorter analysis, both in whole peripheral blood and
      after in vitro activation of T cells and antigen-presenting cells. Results were
      correlated with clinical data. The expression of CD28 on CD4+ and CD8+ cells was
      significantly lower in WG than in HC (CD28+ 81.4% in WG versus 97.9% of CD4+
      cells (P < 0.0001); CD28+ 44.6% in WG versus 68.5% of CD8+ cells (P < 0.00001)),
      both in peripheral blood and after in vitro activation. A lower percentage of
      monocytes was B7-2+ in WG than in HC in peripheral blood, whereas no significant
      differences in the expression of B7-1 and B7-2 were observed after in vitro
      stimulation of monocytes and B cells. After in vitro activation a significantly
      higher percentage of B7-1+ and B7-2+ T cells was seen in WG. There was no
      significant difference in the CTLA-4 expression pattern between WG and HC. The
      percentage of CD28+ lymphocytes correlated negatively with the Disease Extent
      Index cumulated over the course of disease (r = -0.46, P = 0.03), indicating a
      more severe manifestation in patients with lower CD28 expression. Correlations
      with other clinical parameters such as activity or therapy were not seen. WG
      patients show a lack of CD28 expression on T cells and an unusual up-regulation
      of its ligands B7-1 and B7-2 on T cells after in vitro activation as well as a
      lower expression of B7-2 on freshly isolated monocytes compared with HC. These
      features might promote the Th1 cytokine pattern and thereby contribute to
      persistently high levels of immune activation in WG.

PMID- 9764613
TI  - Modulation by proinflammatory cytokines of Fas/Fas ligand-mediated apoptotic cell
      death of synovial cells in patients with rheumatoid arthritis (RA).
AB  - Synovial cell hyperplasia is a characteristic of patients with RA. Excessive
      proliferation of RA synovial cells is, in part, responsible for the synovial cell
      hyperplasia. In addition, synovial cell death that would reduce synovial cell
      number may be defective, leading to the hyperplasia. Thus, the defective control
      of cell death as well as cell proliferation may be of central importance in the
      pathogenesis of RA. In this study we analysed effects of proinflammatory
      cytokines on Fas/Fas ligand (FasL)-induced synovial cell apoptosis, and evaluated
      apoptosis-associated protein expression in the synovial cells in patients with
      RA. RA synovial cells expressed Fas antigen and lymphocytes infiltrating into RA
      synovium expressed FasL. Apoptotic synovial cells were detected within the
      sublining layer of RA synovium. Anti-Fas MoAb induced apoptosis of RA synovial
      cells in vitro, and proinflammatory cytokines tumour necrosis factor-alpha (TNF
      alpha) and IL-1beta, but not IL-6 or IL-8, inhibited the anti-Fas-induced
      apoptosis accompanying up-regulation of Bcl-2 protein expression and reduced
      expression of CPP32 and ICH-1L. Immunohistochemical study revealed that CPP32 and
      ICH-1L were expressed weakly in the RA synovial lining cells compared with
      osteoarthritis (OA) synovial lining cells. Thus, we found that although RA
      synovial cells could die via apoptosis through Fas/FasL pathway, apoptosis of
      synovial cells was inhibited by proinflammatory cytokines present within the
      synovium. Inhibition of apoptosis by the proinflammatory cytokines may contribute
      outgrowth of synovial cells that leads to pannus formation and the destruction of
      joints in patients with RA.

PMID- 9764614
TI  - Sequence analysis of V(4-34)-encoded antibodies from single B cells of two
      patients with systemic lupus erythematosus (SLE).
AB  - SLE is an autoimmune disease characterized by the presence of autoantibodies
      against double-stranded (ds)DNA. A large proportion (approx. 40%) of patients
      with lupus also have increased levels of serum immunoglobulin encoded by the V(4
      34) heavy chain gene, which often fluctuate with disease activity, and this gene
      is utilized by a subset of anti-dsDNA antibodies. In order to probe the nature of
      the V(4-34)-encoded immunoglobulin, B cells were isolated from the blood of two
      patients with active disease, using the 9G4 MoAb specific for the immunoglobulin
      gene product. Following cell picking, single-cell polymerase chain reaction (PCR)
      amplification of cDNA was used to investigate both V(H) and V(L) genes. Sequences
      were obtained from B cells synthesizing IgM (n = 10), IgG (n = 4) and IgA (n =
      1). For V(H), all were derived from V(4-34) as expected, and the isotype-switched
      sequences and 2/6 IgM sequences were somatically mutated. In contrast, V(L) (12
      kappa and 3 lambda) showed a low level of mutation, possibly indicating secondary
      rearrangements. The three most highly mutated V(H) sequences were associated with
      unmutated V(L) sequences. Analysis of the distribution of mutations revealed only
      minor clustering in complementarity-determining regions (CDRs) characteristic of
      antigen selection. The CDR3 lengths of V(H) ranged from five to 19 amino acids,
      and in 3/15 there was evidence of an excess of positively charged amino acids,
      compared with the normal expressed repertoire. Basic amino acids were also found
      at the V(L)-J(L) junctions in 4/15. These findings provide insight into the V(4
      34)-V(L) gene combinations used by B cells in patients with SLE which might have
      clinical relevance.

PMID- 9764615
TI  - A masked randomized comparison of oral and vaginal administration of misoprostol
      for labor induction.
AB  - OBJECTIVE: To test the null hypothesis that administering misoprostol orally or
      vaginally will result in no difference in time to vaginal birth, and to determine
      whether different frequencies of tachysystole and hyperstimulation are associated
      with route of administration. METHODS: Two hundred six women after 37 completed
      weeks' gestation who presented with an indication for induction were randomly
      assigned to receive misoprostol (50 microg) either orally or vaginally every 4
      hours as needed to induce labor. Placebo use and allocation concealment
      accomplished blinding until data analysis was completed. Sample size was
      calculated to allow a two-tailed alpha of .05 and power (1-beta) of 80%. All
      fetal heart rate and uterine activity graphs were classified according to Curtis'
      criteria before induction groups were unmasked. RESULTS: Analysis involved 104
      women in the oral group and 102 in the vaginal group. The mean time (+/-standard
      deviation) to vaginal birth with oral misoprostol was 1072 (+/-593) minutes
      compared with 846 (+/-385) minutes with the vaginal protocol (P=.004). There were
      no significant differences in cesarean rate, epidural use, or neonatal outcomes.
      More frequent tachysystole for 20 minutes (P < .01) and hyperstimulation (P <
      .04) were observed with vaginal misoprostol. No neonatal asphyxia occurred in
      either group. CONCLUSION: Misoprostol effectively induces labor, given orally or
      vaginally. There is a shorter interval to vaginal birth with vaginal application;
      however, the more frequent occurrence of fetal heart rate graph abnormalities in
      this group suggests that, until the optimal dosing interval for vaginal use is
      determined, the preferred route of misoprostol administration might be oral.

PMID- 9764616
TI  - Cervical ripening with mifepristone before labor induction: a randomized study.
AB  - OBJECTIVE: To determine the efficacy and safety of mifepristone for cervical
      ripening in post-term pregnancies. METHODS: Women with post-term pregnancies and
      Bishop scores less than 6 were assigned randomly to mifepristone (41 patients) or
      placebo (42 patients). Mifepristone was given orally in a dose of 400 mg.
      Efficacy was assessed by change in the Bishop score within 48 hours after
      treatment; a score of 6 or greater was considered a "strict" success. An
      "extended" success rate was defined, including all patients with scores of at
      least 6 or those who delivered within 48 hours of treatment. Antenatal safety was
      assessed by fetal heart rate testing before and throughout labor. Neonatal safety
      was assessed by Apgar score, arterial or venous pH of cord blood, and blood
      glucose level during the first 48 hours. Analysis used Student t test for
      continuous variables, Kruskal-Wallis test for ordinal data, and chi2 for
      categoric variables. RESULTS: Strict success was achieved in 10 of 18
      mifepristone patients (55%) evaluated for Bishop score on day 2 versus 8 of 29
      placebo patients (27.5%) (P=.004). Extended success was achieved in 33
      mifepristone patients (80.5%) and 21 placebo patients (50.0%) (P=.004). There
      were no statistical differences with regard to number of cesareans or fetal and
      neonatal safety. CONCLUSION: Mifepristone proved effective for cervical ripening
      and reduced the time to delivery compared with placebo, but it did not improve
      the rate of cesarean. Our study did not include enough pregnancies to reach
      conclusions about fetal or neonatal safety.

PMID- 9764617
TI  - The cost-effectiveness of routine type and screen admission testing for expected
      vaginal delivery.
AB  - OBJECTIVE: To evaluate the cost effectiveness of routine admission type and
      screen testing for expected vaginal delivery. METHODS: A retrospective review was
      conducted in patients transfused with blood during an admission that anticipated
      a vaginal delivery over a 3-year period, at Hutzel Hospital, in Detroit,
      Michigan. RESULTS: Of 16,291 patients admitted for an expectant vaginal delivery,
      76 (.47%) (95% confidence interval [CI] .37%, .58%) required blood transfusion
      during the time of their admission. Medical records of these 76 patients were
      evaluated as to urgency and risk factors. Most of the blood transfusions were
      related to previously identified risk factors, including previous postpartum
      hemorrhage, multiple pregnancies, previous cesarean delivery, abruptio placentae,
      and admission anemia. Four patients received an urgent blood transfusion without
      a previously identifiable risk factor. We found an overall urgent blood
      transfusion rate without admission risk factors to be 2.5 per 10,000 vaginal
      deliveries (95% CI .9 per 10,000, 6.3 per 10,000) CONCLUSION: Routine admission
      type and screen testing for an expected normal vaginal delivery does not seem to
      enhance patient care and should be eliminated for patients without substantial
      risk factors. In the rare event that a patient without a previously identified
      risk factor required an urgent blood transfusion, O negative blood could be given
      in the interim pending formal type and cross match.

PMID- 9764618
TI  - Cesarean delivery and anal sphincter injury.
AB  - OBJECTIVE: Cesarean delivery has been thought to prevent all obstetric anal
      sphincter damage. The objective of this study was to determine the relationship
      between the timing of cesarean during primiparous delivery and injury to the anal
      sphincter mechanism. METHODS: A prospective observational study was conducted,
      using a continence questionnaire and anorectal physiology assessment before and
      six weeks after primiparous delivery. A cohort of 234 women were recruited from
      the antenatal clinics at the National Maternity Hospital, Dublin. Thirty-four
      women delivered subsequently by cesarean, and 200 women by spontaneous vaginal
      delivery. RESULTS: Thirty-four women underwent cesarean delivery without
      attempted vaginal delivery: eight prior to labor and 26 during labor, 17 in early
      labor (cervical dilatation less than 8 cm) and 9 in late labor (dilatation
      greater than 8 cm). No woman delivered by cesarean had altered fecal continence
      postpartum. Anorectal physiology was unaltered in women delivered by elective
      cesarean or cesarean in early labor. Pudendal nerve terminal motor latency was
      prolonged, anal squeeze pressure increment reduced, but vector symmetry index was
      unchanged in women delivered by cesarean delivery late in labor, indicating
      neurologic injury to the anal sphincter mechanism. CONCLUSION: Cesarean delivery
      performed in late labor, even in the absence of attempted vaginal delivery, does
      not protect the anal sphincter mechanism.

PMID- 9764619
TI  - Obstacles to reducing cesarean rates in a low-cesarean setting: the effect of
      maternal age, height, and weight.
AB  - OBJECTIVE: To examine risk factors for elective and nonelective cesarean delivery
      in a population with a low cesarean rate. METHODS: Nulliparous women delivering
      singleton births in Sweden during 1992-93 were included (n=92,623). Logistic
      regression analyses were performed to calculate adjusted odds ratios (ORs) and
      rates of cesarean delivery. RESULTS: The overall cesarean rate was 11.9%. Risks
      for cesarean increased consistently with increasing maternal age, decreasing
      maternal height, and increasing prepregnancy body mass index (BMI). Compared with
      teenagers, the OR of cesarean was 2.6 among women 30-34 years and 4.4 among women
      35 years of age or older. Compared with tall women (greater than 174 cm), the OR
      of cesarean for women 155-164 cm was 2.0, and 4.5 for short women (less than 155
      cm). Compared with lean women (BMI less than 20.0), the ORs of cesarean for
      overweight (BMI 25.0-29.9) and obese women (BMI of at least 30.0) were 1.8 and
      2.4, respectively. Similar risks also were obtained when the analyses were
      restricted to elective or nonelective cesarean deliveries. The effect of
      prepregnancy BMI on cesarean rate was influenced by maternal height: among tall
      women, rates of cesarean increased from 5% among lean women to 11% among obese
      women, whereas corresponding rates among short women were 19% and 36%,
      respectively. The influence of mother's education, type of hospital, and other
      factors was considerably less. CONCLUSION: The increase in maternal age at first
      birth and the weight among young women present obstacles to the reduction of
      cesarean rates in developed countries.

PMID- 9764620
TI  - Maternal and infant complications in high and normal weight infants by method of
      delivery.
AB  - OBJECTIVE: To estimate the population risks of maternal and infant complications
      with the birth of macrosomic (at least 4000 g) compared with normal weight
      infants. METHODS: Term, singleton infants were identified from the state of
      Washington's birth event records database for 1990. Diagnosis codes from the
      Internal Classification of Diseases (9th revision) were used to identify delivery
      method and previously defined complications. We adjusted for maternal demographic
      and clinical factors using multivariable logistic regression to derive the risk
      of each maternal and infant complication. RESULTS: The incidence of macrosomia
      was 13% (8815 of 66,086). Vaginal birth of macrosomic infants was associated with
      low incidence of complications except for shoulder dystocia (11%) and postpartum
      hemorrhage (5%). Postpartum infection was the most common complication for women
      who had cesarean delivery after labor (5%), and complications for women who had
      cesarean without labor were rare (less than 3%). Neonatal complications were
      rare. Among infants with shoulder dystocia, the risks of asphyxia (adjusted
      relative risk [RR] 1.2, 95% confidence interval [CI] 0.6, 2.3), birth trauma (RR
      0.6, 95% CI 0.2, 1.6), long-bone injury (RR 1.2, 95% CI 0.6, 2.4), seizures (RR
      1.0, 95% CI 0.0, 25.0), and facial palsy (RR 2.2, 95% CI 0.2, 44.4) were not
      significantly different for macrosomic and normal weight infants; however,
      macrosomic infants had a significantly increased risk of Erb palsy (RR 3.5, 95%
      CI 1.8, 7.5). CONCLUSION: This population-based study showed that most macrosomic
      infants are delivered vaginally with low rates of maternal and neonatal
      complications. Macrosomic infants have higher rates of Erb palsy, but similar
      rates of other serious complications of shoulder dystocia when compared with
      normal weight infants.

PMID- 9764621
TI  - Regional differences in operative obstetrics: a look to the South.
AB  - OBJECTIVE: To compare operative delivery rates across regions of the United
      States from 1987 to 1994 and to evaluate how the rates of severe obstetric
      lacerations changed during the same period. METHODS: I used diagnosis and
      procedure data from the National Hospital Discharge Survey and natality data from
      the National Center for Health Statistics to describe temporal and regional
      variations in the rates of cesarean, forceps, and vacuum delivery. I described
      temporal trends in the rates of cervical and severe perineal lacerations during
      the same period. I performed exploratory analyses of detailed 1990 data to test
      for regional differences in demographic risk factors that might explain
      differences in operative delivery rates. RESULTS: Between 1987 and 1994, cesarean
      delivery rates fell from approximately 25% to less than 22% in all regions except
      the South. Operative vaginal delivery rates were stable at 10-12% and were
      consistently lowest in the Northeast (8.2% in 1994) and highest in the South
      (12.9% in 1994). Vacuum surpassed forceps deliveries in all regions except the
      South. The rates of cervical and fourth-degree perineal lacerations declined by
      57% and 40%, respectively, whereas the rate of third-degree lacerations did not
      decline. Demographic risk factors for cesarean delivery were no more prevalent in
      the South than in other regions. Age under 25 years was the only demographic risk
      factor for forceps delivery that was more prevalent in the South. CONCLUSION: In
      all but the southern United States, cesarean delivery rates declined and vacuum
      surpassed forceps delivery. These regional differences are not explained by
      differences in demographic risk factors.

PMID- 9764622
TI  - Management of extremely low birth weight infants: perceptions of viability and
      parental counseling practices.
AB  - OBJECTIVE: To determine physician opinions, parental counseling, and medical
      practices for extremely low birth weight (LBW) infants. METHODS: A retrospective
      survey was sent in August 1996 to 450 California physicians practicing
      obstetrics. RESULTS: There was a 41% response rate. The mean thresholds for
      antenatal steroid administration, cesarean delivery for fetal distress and
      delivery room resuscitation were gestational age between 23 and 24 weeks and
      weight close to 500 g. Most obstetricians counsel parents regarding survival,
      resuscitation, and possible death in the delivery room before delivery of an
      extremely LBW infant. Just over 60% of obstetricians believe that parents have a
      role in deciding not to resuscitate an infant born at 22 weeks' gestation, this
      decreases to less than 50% at 24 weeks, and decreases further to less than 30% by
      26 weeks' gestation. Just over 40% of obstetricians report their counseling is
      affected by pediatric opinion, 33% by previous maternal perinatal losses, and
      less than 20% by maternal drug use or lack of prenatal care, and young maternal
      age. Language barriers, parental education level, and family insurance affect
      treatment options in less than 10% of obstetricians. CONCLUSION: Obstetric
      opinions about delivery room resuscitation of extremely LBW infants are
      influenced by birth weight and gestational age thresholds, infant, and parental
      factors. There is a limited willingness by physicians to allow a parental role in
      decision making in the delivery room for extremely LBW infants.

PMID- 9764623
TI  - Effect of maternal hydration on oligohydramnios: a comparison of three volume
      expansion methods.
AB  - OBJECTIVE: To determine the effect of maternal hydration with intravenous (i.v.)
      isotonic fluid, i.v. hypotonic fluid, and oral water on amniotic fluid index
      (AFI) in women with oligohydramnios. METHODS: Patients with low AFI and
      gestational age over 35 weeks without maternal complications were randomized into
      four groups (2 L/2 h i.v. isotonic fluid, 2 L/2 h i.v. hypotonic fluid, 2 L/2 h
      oral water, control). Maternal plasma osmolality, AFI, hematocrit, and hemoglobin
      concentration were measured before and after hydration. RESULTS: Eighty-four
      patients (n=21/group) completed the study without any maternal adverse effects.
      The mean increase in AFI after hydration was significantly greater in the i.v.
      hypotonic and oral water groups (2.8+/-1.9, P < .001; 3.8 +/-1.9, P < .001,
      respectively), but not in the i.v. isotonic group (0.5+/-1.1), compared with the
      control group (0.5+/-1.1). Significant decreases in maternal hematocrit and
      hemoglobin concentration were found only after i.v. isotonic hydration (32.0+/
      2.9 to 29.5+/-2.3, P < .001; 11.0+/-1.6 to 10.1+/-1.4, P < .001, respectively).
      Changes in maternal osmolality correlated with the changes in AFI in both the
      i.v. hypotonic group (r=.58, P < .001) and oral water group (r =.63, P < .001).
      CONCLUSION: Maternal hydration with either i.v. hypotonic fluid or oral water
      increases AFI in oligohydramnios. Maternal osmotic change rather than maternal
      volume expansion had a more direct impact on increasing amniotic fluid volume
      with short-term acute hydration.

PMID- 9764624
TI  - Effects of abuse on maternal complications and birth weight in adult and
      adolescent women.
AB  - OBJECTIVE: To estimate the incidence of physical and sexual abuse in a sample of
      adult and adolescent pregnant women and to determine the relationship between
      abuse and maternal complications and infant birth weight. METHODS: One thousand
      eight hundred ninety-seven women were screened for abuse during pregnancy.
      Maternal complications and infant birth weight were obtained by record review.
      RESULTS: Physical abuse in the past year and/or during pregnancy was reported by
      37.6% of the adolescent and 22.6% of the adult women (P < .001). Abused adult
      women were more likely to have unplanned pregnancies (P < .001) and to begin care
      after 20 weeks (P < .01) than nonabused women. For the aggregate sample of 1597
      for whom birth weights were available, abuse was a significant risk factor for
      low birth weight (LBW) (P < .05) as was poor obstetric history (P < .05). Using
      Institute of Medicine risk factors for LBW, abused adults were more likely to
      have poorer past obstetric histories and to use tobacco, alcohol, and drugs (P <
      .05). Abused adolescents were at greater risk for smoking and first- or second
      trimester bleeding (P < .05). For the aggregate, abused women were at greater
      risk for poor obstetric history, vaginal/cervical infection during pregnancy,
      smoking, and alcohol and drug use. CONCLUSION: More than one-third of the
      adolescent and nearly one-fourth of the adult women reported abuse in the past
      year and/or during pregnancy. Abuse is related to poor obstetric history,
      substance use, and LBW. The short abuse assessment screen detects potential abuse
      in order that interventions can be implemented.

PMID- 9764625
TI  - Prevention of chickenpox in reproductive-age women: cost-effectiveness of routine
      prenatal screening with postpartum vaccination of susceptibles.
AB  - OBJECTIVE: To evaluate economic and clinical outcomes of a program of routine
      prenatal serotesting for varicella and postpartum vaccination of seronegative
      women. METHODS: An analytic cost-effectiveness model was constructed to compare
      the current strategy of no serotesting with 1) selective serotesting of pregnant
      women without a prior history of chickenpox and 2) serotesting of all pregnant
      women. In both serotesting strategies, seronegative women were vaccinated
      postpartum. The model followed a hypothetical cohort of 4 million women over 20
      years. Costs and chickenpox disease outcomes during and outside of subsequent
      pregnancies were considered. The incremental cost-effectiveness (cost per adult
      chickenpox case prevented) of selective serotesting compared with the current
      strategy was measured. RESULTS: Compared to no testing, selective serotesting
      would prevent 43% (48,577 of 112,654) of adult chickenpox cases, save $21.8
      million in discounted medical and work loss costs from the societal perspective,
      and cost $1126 per case prevented from the health payer's perspective (medical
      costs only). The model was sensitive to varicella seroprevalence and incidence of
      chickenpox among susceptible women but was relatively insensitive to the cost of
      serologic testing and vaccination. Compared with selective serotesting, the
      serotest-all strategy would prevent an additional 15,645 cases, at a societal
      cost of $7653 per additional case prevented. CONCLUSION: The selective
      serotesting strategy could prevent nearly half of chickenpox cases among this
      cohort and is cost-saving from the societal perspective. From the health payer's
      perspective, it compares favorably with other generally accepted preventive
      practices. It should be considered for prevention of chickenpox among women of
      childbearing age.

PMID- 9764626
TI  - Amniotic fluid neuron-specific enolase: a role in predicting neonatal neurologic
      injury?
AB  - OBJECTIVE: To determine the relationship between amniotic fluid (AF) neuron
      specific enolase and the development of neonatal intraventricular hemorrhage and
      periventricular leucomalacia. METHODS: Thirty-nine AF samples, obtained from
      women in preterm labor between 24 and 32 weeks' gestation, were analyzed for
      neuron-specific enolase. All women delivered preterm neonates who had
      neurosonograms on the 3rd and 7th days of life. The results of the neurosonograms
      were used to divide the study population first into normal and abnormal groups,
      then into normal, minor, and major brain lesion groups. The groups were compared
      for the median neuron-specific enolase, proportion with values of 6 microg/L or
      more, and other demographic characteristics. RESULTS: There were no differences
      between the groups' maternal and neonatal characteristics. However, the abnormal
      group had significantly higher median value of neuron-specific enolase than the
      normal group (9.5 microg/L and 2.0 microg/L, respectively; P < .001). The median
      neuron-specific enolase levels for the major, minor, and normal groups were 9.75
      microg/L, 6.5 microg/L and 2.0 microg/L, respectively (P < .001). The optimum
      cutoff point, with a sensitivity of 89% and specificity of 100%, was 6 microg/L;
      89% of the abnormals had values of 6 microg/L or more, compared with none of the
      normals (P < .001). The risk of developing intraventricular hemorrhage or
      periventricular leucomalacia was 11.5 times greater when AF neuron-specific
      enolase levels were 6 microg/L or more. CONCLUSION: Amniotic fluid neuron
      specific enolase is a useful marker of neonatal neurologic injury.

PMID- 9764627
TI  - Factors associated with maternal cell contamination in amniocentesis samples as
      evaluated by fluorescent in situ hybridization.
AB  - OBJECTIVE: To determine which patient- and procedure-related factors contribute
      to maternal cell contamination in uncultured amniocentesis fluid. METHODS: One
      hundred thirty amniotic fluid (AF) samples were obtained by three operator
      groups: maternal-fetal medicine faculty (n=50), general obstetrician
      gynecologists (n=50), and obstetrics and gynecology residents supervised by
      maternal-fetal medicine faculty (n=30). These groups were designated "most,"
      "intermediate," and "least experience," respectively. Study variables were
      recorded at the time of the procedure. Amniotic fluid cells from male fetuses
      underwent fluorescent in situ hybridization. Maternal cell contamination was
      calculated by analyzing 100 cells and determining the number of XX and XY cells.
      A control system was created to validate the methods used for AF processing and
      cell counting. RESULTS: Median maternal cell contamination was 2.0%. Maternal
      cell contamination did not vary with body mass index (r=-.13, P=.14), gestational
      age (r=.08, P=.35), or placental location (P=.55). Maternal cell contamination
      was significantly elevated with placental penetration (6.0% compared with 1.0%, P
      < .001), two passes (27.5% compared with 2.0%, P=.002), blood-tinged fluid color
      (14.0% compared with 2.0%, P < .001), and operator inexperience ("intermediate
      experience" compared with "most experience," 4.5% compared with 1.0%, P=.026).
      Maternal cell contamination did not differ between the "most experience" and
      "least experience" groups (1.0% compared with 2.0%, not significant). Concordance
      between detected and actual maternal cell contamination in the control system was
      extremely high (concordance coefficient=0.98, P=.008), confirming the validity of
      the techniques used. CONCLUSION: Our techniques of cell counting and maternal
      cell contamination calculation are accurate. Maternal cell contamination is
      increased with placental penetration, two passes, and operator inexperience.
      However, with expert supervision, inexperienced physicians can perform
      amniocentesis without an increase in maternal cell contamination.

PMID- 9764628
TI  - Cardiac dysfunction in twin-twin transfusion syndrome: a prospective,
      longitudinal study.
AB  - OBJECTIVE: To use serial echocardiography to evaluate prospectively the cardiac
      dysfunction in twin-twin transfusion syndrome and determine its clinical course
      and outcome. METHODS: Twin pregnancies presenting in the second trimester with
      sonographic evidence of twin-twin transfusion syndrome were managed with
      therapeutic reduction amniocenteses. Gestational age at diagnosis and delivery,
      number of amniocenteses performed, volume of amniotic fluid withdrawn,
      placentation, birth weight, hemoglobin at delivery, and perinatal outcome were
      recorded. Serial fetal echocardiography was carried out in a single tertiary
      center. Echocardiographic assessments included cardiac anatomy, chamber size,
      cardiothoracic ratio, interventricular septal thickness, ventricular systolic
      function, and the presence and severity of atrioventricular valve regurgitation.
      Postnatal echocardiograms were obtained on the surviving twins. RESULTS: Twelve
      cases of twin-twin transfusion syndrome were evaluated with serial
      echocardiography. Evidence of cardiac dysfunction was present prenatally in 10
      recipient twins. All of the donor twins had normal fetal echocardiographic
      assessments. The most common abnormalities detected prenatally in recipient twins
      were decreased ventricular function, tricuspid regurgitation, and cardiac chamber
      enlargement. A deterioration of cardiac function was observed in seven recipient
      twins with increasing gestational age. Four of the eight surviving recipient
      twins had persistent postnatal echocardiographic abnormalities on follow-up
      examinations after the first 28 days of life. CONCLUSION: Prenatal cardiac
      dysfunction is common in recipient twins and can be transient, progressive, or
      persistent beyond the neonatal period.

PMID- 9764629
TI  - Randomized comparison of oral and transdermal hormone replacement on carotid and
      uterine artery resistance to blood flow.
AB  - OBJECTIVE: To compare the long-term effects of oral and transdermal hormone
      replacement therapy (HRT) on carotid and uterine vascular impedance. METHODS:
      Sixty-three postmenopausal women were randomized to 1 year's treatment with oral
      or transdermal sequential combined HRT. Carotid and uterine artery pulsatility
      indices (PIs) were assessed by color Doppler at baseline, and after 2, 6, and 12
      months of treatment. Fifty-eight women completed the trial, 27 in the oral and 31
      in the transdermal group. In a subgroup of 30 women, we also performed Doppler
      measurements in the estrogen-progestin combined phase. The study had 90% power to
      detect a difference between treatment groups of 0.05 in the carotid artery and of
      0.25 in uterine artery PI at the 5% significance level. RESULTS: The carotid PI
      decreased significantly (P < .001) and similarly during both regimens. This drop
      was already clearly detectable during the second month, from 0.97 (0.95, 1.01)
      (mean and 95% confidence intervals [CII) to 0.94 (0.91, 0.97) in the oral and
      from 0.98 (0.94, 1.00) to 0.92 (0.89, 0.95) in the transdermal group, but it
      continued up to 12 months (0.85 [0.82, 0.88], 13% of baseline values in the oral
      group and 0.84 [0.81, 0.871, 14% in the transdermal group). In the uterine
      arteries, the drop in PI was steeper and greater and reached its maximum at 6
      months (39% and 40%, respectively). Drops in carotid and uterine PI correlated
      positively with baseline PI values, but were not affected by patient age, time
      from menopause, previous HRT and smoking. Addition of norethisterone acetate did
      not counteract drops in carotid and uterine PI in either group. CONCLUSION: Oral
      and transdermal sequential HRT are similarly effective at 1 year in reducing
      impedance to flow in carotid and uterine circulation. This long-term vascular
      effect might explain how HRT protects women from cardiovascular disease.

PMID- 9764630
TI  - Spinal bone density in women using depot medroxyprogesterone contraception.
AB  - OBJECTIVE: To determine factors possibly associated with reduced bone density in
      women using the injectable contraceptive depot medroxyprogesterone acetate.
      METHODS: In a cross-sectional study, bone mineral density of the lumbar spine was
      measured by dual energy x-ray absorptiometry in 200 current users of depot
      medroxyprogesterone acetate who had used this method of contraception for 2-26
      years and compared with 350 control subjects. Bone density results are expressed
      as standard deviation scores (z score). RESULTS: The bone density was
      significantly lower in depot medroxyprogesterone acetate users (mean z score: 
      0.65, 95% confidence intervals [CI] -0.80, -0.49, P < .001). Bone density was
      significantly reduced in nonsmokers and smokers, and there was no significant
      difference in mean z score between smokers and nonsmokers (mean -0.75 versus 
      0.58, P=.30). Women who had started depot medroxyprogesterone acetate after the
      age of 20 years and who had used it for 15 or fewer years had a significantly
      higher bone density than the remainder of the cohort (mean -0.45 [95% CI -0.62, 
      0.27] versus -1.02 [95% CI -1.32, -0.73], P < .005). Bone density in depot
      medroxyprogesterone acetate users was not related to current age, parity, body
      mass index, calcium intake, or exercise. CONCLUSION: Depot medroxyprogesterone
      acetate use is associated with a significant reduction in bone density, and
      although a high proportion of depot medroxyprogesterone users do smoke, the
      reduction in bone density cannot be explained by smoking. Women who use it for a
      long time and those who start it before peak bone mass is attained may be at
      highest risk.

PMID- 9764631
TI  - A randomized study of tibolone on bone mineral density in osteoporotic
      postmenopausal women with previous fractures.
AB  - OBJECTIVE: To investigate the effects of tibolone on trabecular and cortical bone
      mineral density and on indices of calcium metabolism in postmenopausal women with
      previous fractures. METHODS: In a 2-year, randomized, double-blind, placebo
      controlled, bicenter study, 45 women were treated with tibolone and 43 with
      placebo. All subjects received 800 mg of calcium daily. Trabecular bone mineral
      density of lumbar spine (L1 to L4) and cortical bone mass at the femoral neck
      were assessed by dual energy x-ray absorptiometry at baseline and at 6-month
      intervals. Serum and urinary bone biochemistry variables were also assessed.
      RESULTS: After 2 years, subjects in the tibolone group gained 6.9% bone mass at
      lumbar spine and 4.5% at femoral neck, and respective increases from baseline in
      the placebo group were 2.7% and 1.4%. Tibolone-treated patients gained
      statistically significantly more bone mass than placebo-treated patients in the
      spine and femur. Urinary calcium: creatinine and hydroxyproline:creatinine
      ratios, as well as serum alkaline phosphatase and phosphate levels, were
      significantly reduced with tibolone compared with placebo. CONCLUSION: Tibolone
      induced a significant increase in trabecular (lumbar spine) and cortical (femoral
      neck) bone mass in postmenopausal osteoporotic women compared to placebo,
      suggesting its potential to treat postmenopausal osteoporosis.

PMID- 9764632
TI  - The physician's role in women's decision making about hormone replacement
      therapy.
AB  - OBJECTIVE: To ascertain the sources of information women use when making
      decisions about hormone replacement therapy (HRT). METHODS: A cross-sectional,
      population-based computer-assisted telephone survey of 1082 randomly selected
      women aged 50-80 years (80.3% response rate) was conducted at Group Health
      Cooperative of Puget Sound, a large staff-model health maintenance organization
      in Washington state. RESULTS: Overall, 460 participants (42.5%) were current HRT
      users, 226 (20.9%) were past users, and 396 (36.6%) were never users. Discussions
      with physicians dominated as the major source of information used in decision
      making by current (83.4%) and past (65.5%) users, but were less often cited by
      never users (44.4%); printed material was used by 44.5% of women. Although 72.1%
      of current users reported that the amount of information received from their
      physician about the benefits of HRT was about right, only 48.2% of past users and
      33.6% of never users shared this view (P < .001 current versus never), and 13.3%
      of current users, 32.6% of past users and 58% of never users reported receiving
      no information from their physician about HRT's benefits. CONCLUSION: Hormone
      replacement therapy use is strongly related to interactions between women and
      their physicians. Many women use written materials to make decisions about HRT. A
      large proportion of women feel inadequately informed about HRT's risks and
      benefits. Much work remains to be accomplished toward meeting the goal of the US
      Preventive Services Task Force that all perimenopausal and postmenopausal women
      be counseled about the potential benefits and risks of HRT.

PMID- 9764633
TI  - Effect of the menstrual cycle on creatinine clearance in normally cycling women.
AB  - OBJECTIVE: We assessed changes in creatinine clearance during the menstrual cycle
      of normally cycling women. METHODS: We used a design that precisely identified
      the day of ovulation. Creatinine clearance was measured in 14 subjects on each of
      three days: cycle day 2 or 3, 1 or 2 days before the day of ovulation, and 6 or 7
      days after ovulation. RESULTS: Creatinine clearance was affected significantly by
      the menstrual cycle (P=.02), but the degree of this effect was modest. Mean (+/
      standard error of mean) early follicular, preovulatory, and midluteal creatinine
      clearance values were 135+/-4, 131+/-5, and 142+/-5 mL/min, respectively, and
      only the difference between the preovulatory and midluteal values was
      significant. These changes in creatinine clearance were attributable largely to
      changes in creatinine excretion and not to changes in plasma creatinine
      concentrations. CONCLUSION: Despite the statistically significant luteal phase
      increase, creatinine clearance does not change in a clinically important manner
      during the normal menstrual cycle. Specifically, there is no substantial decrease
      in creatinine clearance around the time of ovulation.

PMID- 9764634
TI  - Cancer among first-degree relatives of probands with invasive and borderline
      ovarian cancer.
AB  - OBJECTIVE: The familial clustering of ovarian, breast, endometrial, colon; and
      prostate cancer was compared in first-degree relatives of probands with invasive
      and borderline ovarian cancer to determine coaggregation. METHODS: Probands
      (n=392), who had been patients in the Division of Gynecologic Oncology at
      Washington University, were ascertained consecutively. Family history on 2192
      first-degree relatives was collected by personal interviews of the probands and
      other family members. Estimates of prevalence of cancers in first-degree
      relatives of the two proband groups were compared. Survival analysis was used to
      examine the age-at-onset distribution of each cancer in relatives of invasive
      probands versus relatives of borderline probands. RESULTS: Among the relatives
      were 24 cases of ovarian cancer, 46 cases of breast cancer, 13 cases of
      endometrial cancer, and 25 and 28 cases of colon and prostate cancer,
      respectively. There were no significant differences in the prevalence of any of
      these cancers in relatives of the invasive and borderline probands. Cumulative
      lifetime risk estimates did not differ between the relatives of the two groups
      for any cancers. Age-at-onset of ovarian cancer did not differ between probands
      with positive family histories of the five cancers and those with negative
      histories. The inability to reject the null hypothesis of no differences in the
      first-degree relatives of our two study groups might be from insufficient power
      to detect small differences, given our sample size. CONCLUSION: These results
      suggest that relatives of patients with invasive and borderline ovarian cancer
      might share similar cancer risks and age-at-onset distributions.

PMID- 9764635
TI  - BRCA1 gene mutations in women with papillary serous carcinoma of the peritoneum.
AB  - OBJECTIVE: To compare BRCA1 mutations in papillary serous carcinoma of the
      peritoneum and papillary serous ovarian carcinoma. METHODS: Germline DNA from 17
      consecutive patients with peritoneal carcinoma was screened for mutations in the
      BRCA1 gene using single-strand conformation polymorphism analysis. Shifted DNA
      bands were sequenced. Patients with germline BRCA1 mutations were screened for
      allelic loss in tumor DNA at the BRCA1 locus. RESULTS: Two of the 17 patients
      (11%, 95% confidence interval 0.07, 0.37) exhibited the 185 delAG germline BRCA1
      mutation described in the Ashkenazi Jewish population. The family history of one
      patient was notable for a mother and five aunts with breast or ovarian cancer.
      The other patient had a personal history of breast cancer. Both patients
      exhibited allelic loss of the normal BRCA1 allele in their tumor. A third patient
      was found to have a previously undescribed exon 11 single base pair substitution
      at nucleotide 1239 (CAG to CAC) resulting in a missense mutation (Gln to His).
      The patient had no family or personal history of breast or ovarian cancer, and
      her tumor did not exhibit loss of heterozygosity. CONCLUSION: Germline BRCA1
      mutations occur in papillary serous carcinoma of the peritoneum with a frequency
      comparable to the BRCA1 mutation rate in ovarian cancer. Although the penetrance
      is unknown, peritoneal carcinoma should be considered a malignancy expressed in
      the familial breast ovarian cancer syndrome.

PMID- 9764636
TI  - Evaluation of atypical and low-grade cervical cytology in private practice.
AB  - OBJECTIVE: To evaluate the adequacy of cytology alone for diagnosis of grade of
      cervical intraepithelial neoplasia (CIN) and to study performance of cytology,
      human papillomavirus (HPV) testing, and colposcopy in the evaluation of cytologic
      findings suggesting low-grade squamous intraepithelial lesions (SIL), or atypical
      squamous (ASCUS) or atypical glandular (AGCUS) cells of undetermined
      significance. METHODS: Standard gynecologic and cytologic evaluation and
      colposcopic inspection as an additional screening approach were performed on
      women with no prior hysterectomies screened in a private practice between January
      1, 1993, and August 1, 1995. Among these 7651 women, 367 had ASCUS, AGCUS, or SIL
      cytology or clinically or colposcopically visible cervical lesions. Sensitivity,
      specificity, and relative risk of CIN in the 367 women were compared by
      colposcopic, cytologic, histologic and virologic diagnoses. RESULTS: The
      sensitivity of all non-negative Papanicolaou smears for CIN 2-3 and cancer was
      92%, combined cytologic categories of high- and low-grade SIL were 59%, and high
      grade SIL alone was 22%. Colposcopy was performed in all 367 patients, and
      positive findings led to biopsies in 48%. Colposcopy of patients with ASCUS
      increased detection of CIN 2-3 by 32% and CIN 1 by 48%. Cervical cytology was
      false negative in 8% of patients with CIN 2-3 and in 14% of those with CIN 1.
      These cases of CIN were detected by screening colposcopic inspection. High-risk
      HPV DNA was positive in 41% of women with CIN 2-3, and in 25% of those with CIN
      1. The positive predictive value of ASCUS cytology increased from 5% to 42% for
      CIN 2-3 and from 30% to 85% for all grades of CIN in patients carrying high-risk
      HPV DNA. Virologic studies did not add to an increase in the sensitivity for CIN
      2-3 among women in the low- and high-grade SIL cytology groups. CONCLUSION:
      Because of the limited sensitivity of the high-grade SIL cytologic category for
      CIN 2-3, we recommend that all women with ASCUS, AGCUS, low- or high-grade SIL
      cytology be recalled for colposcopy, with biopsy only when indicated by
      colposcopic findings.

PMID- 9764637
TI  - Clinical and urodynamic predictors of delayed voiding after fascia lata
      suburethral sling.
AB  - OBJECTIVE: To determine the time to resumption of normal voiding after a fascia
      lata sling and whether any clinical, operative, or urodynamic variables predict
      it. METHODS: Between January 1993 and September 1996, 62 women underwent fascia
      lata suburethral sling operations for intrinsic sphincter deficiency or recurrent
      stress incontinence. The demographic, operative, and urodynamic data of 61 of
      these patients were analyzed. RESULTS: The mean number of days to resumption of
      normal voiding was ten. Three patients (5%) developed permanent retention.
      Patients 65 years and older were more likely than younger patients to have
      prolonged catheterization (16 versus 7 days, P=.008). Women who had additional
      procedures voided at a mean of 15 days compared to nine days for those having
      slings only (P=.029). A preoperative urine flow rate less than 20 mL/sec was
      associated with late voiding. There was no significant relationship between
      preoperative voiding mechanism and voiding time. CONCLUSION: Resumption of normal
      voiding occurred earlier than reported by others. Age over 65 years, additional
      surgical procedures, and low peak flow rates were risk factors for delayed
      voiding. Time to normal voiding was independent of the preoperative voiding
      mechanism.

PMID- 9764638
TI  - The effects of birth on urinary continence mechanisms and other pelvic-floor
      characteristics.
AB  - OBJECTIVE: To determine the effects of delivery on bladder and anorectal
      functions. METHODS: One hundred forty-nine nulliparas were studied once during
      pregnancy and again about 9 weeks after delivery by means of questionnaire,
      clinical examination, perineal sonography, urethral pressure profiles, and
      recording of intravaginal and intra-anal pressures during pelvic-floor
      contraction. RESULTS: Stress urinary incontinence was present in 46 patients
      (31%) during pregnancy and persisted in ten of them after delivery. After vaginal
      delivery, urinary and fecal incontinence were present in 36% and 4% of forceps
      delivered women, respectively, and in 21% and 5.5% of spontaneously delivered
      women. Bladder neck mobility was increased significantly after all vaginal
      births, whereas bladder neck position at rest was lowered only in forceps
      delivered women. Functional urethral length was decreased in the supine and
      standing positions after spontaneous and forceps deliveries. Otherwise, indices
      of urethral sphincter function were unchanged or improved after vaginal delivery.
      A significant decrease in intravaginal pressure and in intra-anal pressure was
      observed in all vaginally delivered women. The intra-anal pressure decrease
      correlated significantly with infant weight (r=0.24, P=.01). Women who underwent
      cesarean had no specific complaints and only slight modifications of these
      measurements. CONCLUSION: After spontaneous and instrumental deliveries, 21% and
      34% of women complained of stress urinary incontinence and 5.5% and 4% reported
      fecal incontinence, respectively. Substantial bladder neck hypermobility was
      present together with diminished functional urethral length and intravaginal and
      intra-anal pressures. Only 22% of patients with stress urinary incontinence
      during pregnancy had such incontinence after delivery.

PMID- 9764639
TI  - Extraperitoneal laparoscopic colposuspension: short-term cure rate,
      complications, and duration of hospital stay in comparison with Burch
      colposuspension.
AB  - OBJECTIVE: To compare duration of surgery, length of hospital stay,
      complications, and short-term cure rate of extraperitoneal laparoscopic
      colposuspension with that of Burch colposuspension. METHODS: We retrospectively
      reviewed 157 consecutive cases of extraperitoneal laparoscopic (n=70) or Burch
      colposuspension (n=87) performed between January 1, 1995, and June 30, 1997. Cure
      rate was assessed by history, physical examination, and questionnaire. Patients
      not requiring the use of pads were considered continent. Cure rates were compared
      in the entire group, whereas complications, duration of surgery, and length of
      stay were compared only in subgroups undergoing colposuspension alone. Results
      were analyzed statistically. RESULTS: The mean times to follow-up were 12.9
      months (laparoscopic group) and 16.3 months (Burch group). At last follow-up, 64
      of 70 (91.4%) of the laparoscopic and 80 of 87 (92%) of the Burch colposuspension
      group were continent. In patients who underwent colposuspension alone, results
      were as follows for those who underwent laparoscopic (19) and Burch (21)
      procedures, respectively: average duration of surgery, 49.2 compared with 62.6
      minutes (P < .03); average hospital stay, 14 hours compared with 2.7 days (P <
      .001); average postoperative disability period, 1.6 weeks compared with 4.7 weeks
      (P < .001); incidence of complications, 15.8% compared with 33.3% (P=.170).
      CONCLUSION: Extraperitoneal laparoscopic colposuspension, compared with Burch
      colposuspension, resulted in similar short-term cure rates and complications,
      shorter duration of surgery, hospital stay, and convalescence. It is a feasible
      option in treatment of stress urinary incontinence when laparotomy is not
      required.

PMID- 9764640
TI  - The "remote control" laparoscopic bag: a simple technique to remove intra
      abdominal specimens.
AB  - BACKGROUND: To facilitate extraction and avoid intra-abdominal spillage during
      laparoscopic removal of adnexal masses, various designs and sizes of endopouches
      (bags) have been used. We describe a simple technique using a special
      laparoscopic bag that requires no additional instruments to hold, open, or close
      the bag. TECHNIQUE: The laparoscopic bag can be prepared from the sterile
      wrapping of disposable surgical items (eg, suction tubing) and two long sutures.
      The bag is introduced through the cannula of the laparoscope and is unfurled. By
      manipulation of the two long sutures threaded through the neck of the bag, the
      surgeon can easily open and close it. EXPERIENCE: We have performed this
      procedure "in vitro" on many occasions to ensure that the drawstring technique
      works. The laparoscopic bag has been used successfully in three patients
      undergoing oophorectomy and salpingo-oophorectomy. Our experience shows that this
      type of laparoscopic bag is easy to use and safe, reduces operative time, and is
      cost effective. Because the bag can be large, operating inside the bag is also
      possible. CONCLUSION: Our drawstring design allows easy manipulation of a
      laparoscopic bag to facilitate its opening and closure.

PMID- 9764641
TI  - New concepts in the treatment of uterine leiomyomas.
AB  - Uterine leiomyomas are a common clinical occurrence for gynecologists. The
      current approach to treating these neoplasms is shaped by classic surgical
      principles and the knowledge that these tumors are responsive to the gonadal
      steroids estrogen and progesterone. As knowledge of leiomyomas advances through
      the techniques of molecular biology and molecular genetics, new concepts are
      developed that go beyond just myomas as steroid-responsive tumors. Understanding
      the molecular events involved in the transformation of a normal myometrial cell
      into a neoplastic cell and the subsequent growth of these leiomyoma cells will be
      important in determining the pathogenesis of these tumors and providing new
      targets for treatment. Knowing the role of peptide growth factors, including
      basic fibroblast growth factor and transforming growth factor-beta, in the
      pathogenesis of leiomyoma-related symptoms might lead to new treatments targeting
      these molecules or their receptors. As the effects of genes, including HMGIC and
      HMGI(Y), are determined; new treatments to prevent leiomyoma formation or growth
      may be developed. As we gain understanding of the molecular events that cause
      benign gynecologic conditions such as leiomyomas, safer and more effective
      treatments might be found as we enter the 21st century.

PMID- 9764642
TI  - Motivation and reward factors that affect private physician involvement in an
      obstetrics and gynecology clerkship.
AB  - OBJECTIVE: The Department of Obstetrics, Gynecology and Reproductive Biology in
      the College of Human Medicine at Michigan State University has 163 private
      practice obstetricians and gynecologists teaching clerkship students, on a
      volunteer basis, in six Michigan cities. The department wanted to learn what
      motivates their involvement in the department's required clerkship, to determine
      their attitudes toward private office teaching, and to determine what incentives
      are important to them in their role as educators. METHODS: The department
      developed a questionnaire that was mailed to the obstetricians and gynecologists
      involved in its required obstetrics and gynecology clerkship. The response rate
      was 68% (111 of 163). RESULTS: Respondents indicated personal and professional
      motivations transcend financial considerations. Almost 60% of respondents
      reported at least a moderate interest in teaching in their private offices in
      spite of perceived negative consequences, such as adverse impact on patient flow.
      The incentives in which private practitioners were primarily interested included
      seminars or meetings that would enhance their teaching skills or educational
      contribution; discounts on computers, athletic and cultural events, and books;
      and university support in producing educational materials. CONCLUSION:
      Departments using private practitioners in medical education need to nurture the
      relationship continually with their volunteer faculty. Faculty development aimed
      at assisting private practitioners with their teaching role in the ambulatory
      care setting might be extremely worthwhile. Financial remuneration may not be key
      to attracting and retaining volunteer faculty. The implications of pay
      arrangements for volunteer faculty should be considered carefully before
      implementation.

PMID- 9764643
TI  - Quantifying faculty teaching time in a department of obstetrics and gynecology.
AB  - OBJECTIVE: The goal of this project was to develop a reproducible system that
      measures quantity and quality of teaching in unduplicated hours, such that
      comparisons of teaching activities could be drawn within and across departments.
      Such a system could be used for allocating teaching monies and for assessing
      teaching as part of the promotion and tenure process. METHODS: Various teaching
      activities, including time spent in clinic, rounds, and doing procedures, were
      enumerated. The faculty were surveyed about their opinions on the proportion of
      clinical time spent in teaching. The literature also was reviewed. RESULTS: Based
      on analysis of the faculty survey and the literature, a series of calculations
      were developed to divide clinical time among resident teaching, medical student
      teaching, and patient care. The only input needed was total time spent in the
      various clinical activities, time spent in didactic activities, and the resident
      procedure database. CONCLUSION: This article describes a simple and fair database
      system to calculate time spent teaching from activities such as clinic, ward
      rounds, labor and delivery, and surgery. The teaching portfolio database
      calculates teaching as a proportion of the faculty member's total activities. The
      end product is a report that provides a reproducible yearly summary of faculty
      teaching time per activity and per type of learner.

PMID- 9764644
TI  - Preterm contractions in community settings: I. Treatment of preterm contractions.

PMID- 9764645
TI  - Necrotizing genital ulcerations in a premenarcheal female with mononucleosis.
AB  - BACKGROUND: Two cases of genital ulcerations caused by Epstein-Barr virus have
      been reported previously, one in a sexually active 23-year-old and another in a
      14-year-old practicing cunnilingus. CASE: We report a case of Epstein-Barr virus
      genital ulcerations in a premenarcheal virgin. Her systemic symptoms were
      atypical for mononucleosis. Necrotizing genital ulcerations preceded pharyngitis
      and oral lesions. Cervical adenopathy, fever, and splenomegaly never developed
      despite serologic evidence of acute mononucleosis. CONCLUSION: Genital
      ulcerations can be the initial manifestation of Epstein-Barr virus in adolescents
      who are neither sexually active nor immunocompromised.

PMID- 9764647
TI  - Thrombosis of the pelvic veins associated with a large myomatous uterus.
AB  - BACKGROUND: Deep vein thrombosis is a rare indication for hysterectomy. CASE: A
      45-year-old woman presented with a myomatous uterus of 20 gestational weeks' size
      that was compressing the pelvic veins directly and causing thrombosis. After
      preparation of the patient with anticoagulants and installation of an umbrella
      device in the inferior vena cava, we performed an uneventful abdominal
      hysterectomy. CONCLUSION: Pelvic deep vein thrombosis is a rarely reported
      complication of myomatous uterus. It can be managed successfully by
      anticoagulants, placement of an umbrella device in the inferior vena cava, and
      hysterectomy, as in our case.

PMID- 9764646
TI  - Chronic vaginal candidiasis responsive to biotin therapy in a carrier of
      biotinidase deficiency.
AB  - BACKGROUND: Many patients experience recurrent or persistent episodes of vaginal
      candidiasis. Some of these women might be carriers of an inborn error of biotin
      metabolism (either biotinidase deficiency or holocarboxylase synthetase
      activity). These women might benefit from administration of pharmacologic amounts
      of biotin. CASE: A 38-year-old gravida 2, para 2 carrier of biotinidase
      deficiency presented with a 14-month history of persistent vaginal candidiasis,
      despite appropriate therapy. After 3 months of pharmacologic doses of biotin, her
      symptoms resolved completely. CONCLUSION: Given that 1 in every 123 individuals
      is predicted to be a carrier of biotinidase deficiency, there might be other
      women with chronic vaginal candidiasis who will respond to biotin administration.

PMID- 9764648
TI  - Hydropic degenerating leiomyoma presenting as pseudo-Meigs syndrome with elevated
      CA 125.
AB  - BACKGROUND: Leiomyomas rarely cause pseudo-Meigs syndrome. Increased levels of CA
      125 often are associated with some types of malignancy. No reported case of
      pseudo-Meigs syndrome presenting with hydropic degeneration of uterine leiomyoma
      and an elevated CA 125 level could be found on a MEDLINE search. CASE: A 46-year
      old woman presented with a pleural effusion and a pelvic mass measuring 30 x 18
      cm. Preoperative evaluation was remarkable for a CA 125 level of 254 U/mL. At
      laparotomy, the diagnosis was a benign leiomyoma with focal hyaline and extensive
      hydropic degeneration. Her pleural effusion resolved completely by 4 months
      postoperatively. CONCLUSION: Pseudo-Meigs syndrome can present with an elevated
      CA 125 level.

PMID- 9764649
TI  - Suburethral abscess: a complication of periurethral collagen injection therapy.
AB  - BACKGROUND: Urinary tract infection after collagen injection is well documented.
      Other adverse reactions are rare. CASES: Three women experienced suburethral
      abscess after repeat periurethral injections. All patients received local skin
      preparation and postprocedural antibiotics. Symptoms failed to resolve with
      antibiotics. The first two patients presented after 5 weeks and 10 days with
      irritative voiding symptoms and a tender suburethral swelling. The first patient
      was treated with excision. Spontaneous rupture into the urethra occurred with the
      second. The third woman presented with acute urinary retention at 102 days. A
      large suburethral mass was drained successfully in the office. CONCLUSION:
      Suburethral abscess may be a delayed complication of periurethral collagen
      injections, not preventable by postprocedural antibiotics. Drainage is required.

PMID- 9764650
TI  - Hemochromatosis and male infertility.
AB  - BACKGROUND: The clinical association of hemochromatosis and infertility is rare.
      Hemochromatosis may affect fertility through a variety of mechanisms. CASE: A 44
      year-old man and his 36-year-old wife presented with primary infertility of 7
      years' duration. The husband was diagnosed as having idiopathic hemochromatosis,
      abnormal glucose tolerance, and hypogonadism accompanied by impotence, retrograde
      ejaculation, and azoospermia. Treatment consisted of phlebotomies followed by
      gonadotropins, which corrected retrograde ejaculation and improved semen
      characteristics. Concomitant pelvic factors in the woman were corrected
      endoscopically. After failure of pregnancy with ovulation stimulation and
      intrauterine inseminations, a singleton pregnancy was achieved by in vitro
      fertilization, augmented with intracytoplasmic sperm injection. CONCLUSION: This
      case underscores the need to consider advanced reproductive technologies after
      the failure of specific, first-line therapeutic options in infertile couples.

PMID- 9764651
TI  - Dysgerminoma with syncytiotrophoblastic giant cells arising from 46,XX pure
      gonadal dysgenesis.
AB  - BACKGROUND: Dysgerminoma with syncytiotrophblastic giant cells is a rare ovarian
      tumor. Only ten cases of this tumor have been reported, and all tumors developed
      in normal ovaries. This report presents a case of dysgerminoma with
      syncytiotrophoblastic giant cells arising in a patient with 46,XX pure gonadal
      dysgenesis. CASE: An 18-year-old phenotypic female of normal height without
      somatic anomalies with nonfunctional ovaries underwent a bilateral gonadectomy
      for a right ovarian tumor and left streak gonad. The tumor revealed a
      dysgerminoma containing scattered syncytiotrophoblastic giant cells. Her serum
      hCG was elevated, and hCG was demonstrated within syncytiotrophoblastic giant
      cells immunohistochemically. The clinical diagnosis was stage Ia dysgerminoma
      with syncytiotrophoblastic giant cells. Her karyotype was 46,XX and the sex
      determining region Y gene was not detected in tumor DNA by polymerase chain
      reaction analysis. CONCLUSION: This rare gonadal tumor may arise from dysgenetic
      gonads in addition to gonadoblastoma and pure dysgerminoma. It is an example of
      tumorgenesis in pure gonadal dysgenesis with no identifiable Y chromosome
      component.

PMID- 9764652
TI  - Fertility options for patients with stages IA2 and IB cervical cancer:
      presentation of two cases and discussion of technical and ethical issues.
AB  - BACKGROUND: Ten percent to 15% of women diagnosed with cervical cancer are in
      their childbearing years. Traditional therapy for stage IA2 and IB lesions,
      radical hysterectomy, negates future fertility potential. Assisted reproductive
      technology might offer these women fertility options. CASES: Two cases of young
      nulliparous women with stage IA2 cervical cancer, who underwent ovarian
      stimulation and oocyte retrieval followed by radical hysterectomy, were presented
      to illustrate the technical difficulties of oocyte stimulation and retrieval in
      the setting of cervical carcinoma. CONCLUSION: Many issues should be considered
      when counseling a woman with early-stage cervical cancer about future fertility.
      These include ethical issues of embryo freezing and gestational surrogacy and
      practical issues of ovarian preservation and transposition. No current guidelines
      exist to identify appropriate candidates for assisted reproductive technology in
      this setting.

PMID- 9764653
TI  - Psammocarcinoma with an aggressive course.
AB  - BACKGROUND: Psammocarcinoma is an unusual variant of serous cystadenocarcinoma
      characterized by heavy deposits of psammoma bodies. This disease has been
      suggested to be similar to carcinomas of low malignant potential in its indolent
      clinical course. We present this case report of an aggressive course of this
      disease to alert others that psammocarcinoma may not always follow a benign
      course. CASE: A 66-year-old woman underwent staging laparotomy for bilateral
      ovarian cystadenofibromata with rare foci of borderline serous tumors and several
      small bowel peritoneal surface nodules showing infiltrating psammocarcinoma. She
      was not recommended for adjuvant therapy because of the previously reported
      indolent course of this disease. Eighteen months later she represented with small
      bowel obstruction and underwent an exploratory laparotomy that demonstrated
      diffuse recurrence of the psammocarcinoma. CONCLUSION: Psammocarcinoma may have a
      more aggressive course than has been suggested. Patients with this disease should
      have optimal tumor debulking. There may be a role for adjuvant therapy in its
      treatment.

PMID- 9764654
TI  - Encouraging response of an advanced steroid-cell tumor to GnRH agonist therapy.
AB  - BACKGROUND: Chemotherapy for steroid tumors of unspecified type has met with
      limited success and the overall prognosis has been poor. CASE: A patient with a
      virilizing steroid tumor, otherwise unspecified, with demonstrated progressive
      disease after surgical debulking. Treatment with multiagent chemotherapy failed,
      but the patient subsequently had a robust response to GnRH agonist therapy.
      CONCLUSION: GnRH analogue treatment should be considered prior to cytotoxic
      chemotherapy in cases of steroid tumor, not otherwise specified.

PMID- 9764655
TI  - Aborted leiomyosarcoma after treatment with leuprolide acetate.
AB  - BACKGROUND: Leuprolide acetate has been used to decrease uterine size and shrink
      leiomyomata. In carefully selected patients, its treatment benefits are well
      recognized. However, if leuprolide acetate is inadvertently given to a patient
      with an unsuspected leiomyosarcoma, complications may occur. CASE: A patient
      presumed to have leiomyomata was treated with monthly injections of leuprolide
      acetate. In the third month of treatment, unusual manifestations, including
      increased bleeding, aborting mass, urinary retention, and severe pain, occurred
      suggesting a possible malignancy and requiring immediate operation. CONCLUSION:
      The use of leuprolide acetate can delay the diagnosis and treatment of
      leiomyosarcoma and thus may increase the risk of morbidity and affect the
      treatment outcome of patients with leiomyosarcoma. The histologic changes
      ascribed to leuprolide acetate treatment in leiomyomata also were seen in this
      leiomyosarcoma.

PMID- 9764656
TI  - Metastatic uterine leiomyosarcoma presenting as a primary sarcoma of the parotid
      gland.
AB  - BACKGROUND: Leiomyosarcoma of the uterus has a high metastatic potential to
      distant sites due to its tendency for hematogenous spread. CASE: A 49-year-old
      woman presented with an enlarging parotid mass, diagnosed originally as a primary
      fibrosarcoma. Six years later, she developed pulmonary metastases and heavy,
      abnormal uterine bleeding. At hysterectomy, a uterine leiomyosarcoma, identical
      morphologically to the previous lesions, was identified. All tumors showed
      similar immunohistochemical staining, suggesting the metastatic nature of the
      original parotid tumor. CONCLUSION: This rare case of uterine leiomyosarcoma,
      presenting as a primary parotid sarcoma, underscores the importance of
      considering the possibility of a uterine primary tumor when a sarcoma arises in
      an organ in which these tumors are unusual.

PMID- 9764657
TI  - Conservative management of uterine rhabdomyosarcoma.
AB  - BACKGROUND: Rhabdomyosarcomas are rare, malignant tumors derived from primitive
      myogenic precursors and are the most common soft tissue neoplasms in children and
      adolescents. We used primary chemotherapy and subsequent removal of the residual
      polypoid mass to treat an adolescent female with uterine rhabdomyosarcoma. CASE:
      A 15-year-old white adolescent who presented with a polypoid uterine
      rhabdomyosarcoma was treated with vincristine, etopside, and ifosfamide, after
      which the residual polypoid mass was removed. CONCLUSION: Treating adolescent
      females with a polypoid uterine rhabdomyosarcoma with primary chemotherapy
      followed by removal of the residual mass preserves reproductive function and
      should be considered.

PMID- 9764658
TI  - Catamenial fevers associated with a uterine smooth muscle tumor of undetermined
      malignant potential.
AB  - BACKGROUND: Pyrexia associated with solid and hematogenous neoplasms are a well
      recognized clinical condition. Menstrually related (catamenial) fevers have not
      been reported previously. CASE: A 52-year-old woman with a history of stage I
      breast cancer on adjuvant tamoxifen citrate presented with recurrent fevers
      associated with menses. An extensive evaluation of possible causes, including
      recurrent breast cancer and infectious, collagen-vascular, and drug-related
      sources, initially was unrevealing. A gynecologic evaluation identified a uterine
      tumor, which appeared to be a cellular leiomyoma on hysteroscopic biopsy. The
      catamenial fevers resolved immediately after hysterectomy. A uterine smooth
      muscle tumor of undetermined malignant potential was identified on pathology.
      CONCLUSION: Smooth muscle tumors of the myometria are a rare cause of menstrual
      fevers.

PMID- 9764659
TI  - Coagulopathy secondary to vitamin K deficiency in hyperemesis gravidarum.
AB  - BACKGROUND: Hyperemesis gravidarum is a condition of pregnancy characterized by
      excessive nausea and vomiting, which can be associated with malnutrition. Vitamin
      K deficiency is a known complication of malnutrition as well as a known cause of
      coagulopathy. To date, there is no reported case in the literature of vitamin K
      deficiency in hyperemesis gravidarum. CASE: A woman at 15 weeks' gestation
      presented with hyperemesis gravidarum complicated by an episode of severe
      epistaxis. Investigation revealed coagulopathy secondary to vitamin K deficiency.
      The coagulopathy resolved after vitamin K replacement, with complete correction
      of all clotting factors. CONCLUSION: Vitamin K deficiency and coagulopathy should
      be considered in women with hyperemesis gravidarum who present with a bleeding
      diathesis. Prophylactic vitamin K replacement should be considered in cases in
      which hyperemesis is severe and protracted.

PMID- 9764660
TI  - Burkitt lymphoma in pregnancy.
AB  - BACKGROUND: Burkitt lymphoma during pregnancy is a rare event, and outcomes have
      been poor. However, few patients were treated by current standards, with nearly
      half receiving single-agent cyclophosphamide or no chemotherapy. CASE: A patient
      with Burkitt lymphoma presenting at 11 6/7 weeks' gestation was treated with
      surgical resection of all visible disease and cytotoxic combination chemotherapy.
      The patient was disease free at 1 year after diagnosis. CONCLUSION: When Burkitt
      lymphoma is encountered in pregnancy, immediate cytotoxic combination
      chemotherapy is indicated.

PMID- 9764661
TI  - Acute intentional iron overdose in pregnancy.
AB  - BACKGROUND: Although iron is the second most common overdose agent in pregnancy,
      the obstetric literature does not reflect current management of this emergency.
      CASE: A 27-year-old woman, para 0-3-4-3, at 27 weeks' gestation ingested 24 mg/kg
      of elemental iron in a suicide attempt. Therapy with crystalloid hydration,
      gastric lavage, and intravenous deferoxamine chelation treated the overdose
      without maternal or fetal complications. CONCLUSION: Pregnancy should not alter
      therapy for acute iron overdose. Deferoxamine administered in the third trimester
      is not associated with perinatal complications and is potentially life saving.

PMID- 9764662
TI  - Successful pregnancy outcome after complicated varicella pneumonia.
AB  - BACKGROUND: Maternal and fetal morbidity and mortality associated with varicella
      pneumonia in the peripartum period are increased further with multiple
      complications. CASE: The patient had varicella pneumonitis acquired at 32 weeks'
      gestation and complicated by bacterial superinfection, adult respiratory distress
      syndrome, endotoxin shock, and bronchiolitis obliterans organizing pneumonia.
      CONCLUSION: Aggressive, timely management of respiratory failure, control of
      infection, correction of endotoxin shock, treatment of biopsy-proven
      bronchiolitis obliterans organizing pneumonia, and obstetric intervention for
      fetal compromise produced a good outcome for mother and infant.

PMID- 9764663
TI  - Isolated pulmonary cryptococcosis in pregnancy.
AB  - BACKGROUND: Isolated pulmonary cryptococcosis in an immunocompetent parturient
      host is a rare event. Little is known about this condition, its prognosis, and
      its treatment in the immunocompetent pregnant woman. CASE: A 28-year-old woman,
      para 3, was diagnosed with isolated pulmonary cryptococcosis postpartum. She had
      delivered a healthy neonate at term who revealed no clinical features compatible
      with maternal-fetal transmission. The woman was monitored closely throughout the
      course of her disease and radiogic, clinical, and serologic resolution was
      achieved after treatment with fluconazole. CONCLUSION: Patients with pulmonary
      cryptococcosis present with clinical pictures similar to other well-known
      diseases such as septic pulmonary emboli or choriocarcinoma. Treatment with
      triazole antifungal therapy yielded favorable results in our patient with this
      rare condition.

PMID- 9764664
TI  - New sonographic findings in a fetus with an interstitial deletion in the long arm
      of chromosome 14.
AB  - BACKGROUND: Interstitial deletions of 14q in which band 14q31 is deleted are
      uncommon. Malformations such as atrial septal defect, horseshoe kidney, and
      cryptochidism have been reported. CASE: We evaluated sonographically the fetus of
      a 22-year-old woman between 16 and 20 weeks' gestation. This imaging showed
      marked dilation of the bladder with mild bilateral hydronephrosis and bilateral
      dilation of the lateral ventricles. In an amniotic fluid specimen obtained at 17
      weeks, chromosomal analysis showed an interstitial deletion of chromosome 14
      including band 14q31, designated 46,XY,del(14)(q24.3q32.1). CONCLUSION: This
      first-reported fetal case of interstitial deletion in chromosome 14 including
      band 14q31 showed anomalies not seen in the reported postnatal cases.

PMID- 9764665
TI  - Unconjugated estriol as an indication for prenatal diagnosis of steroid sulfatase
      deficiency by in situ hybridization.
AB  - BACKGROUND: Undetectable or very low unconjugated estriol (E3) levels in routine
      maternal serum screening are associated with steroid sulfatase deficiency,
      miscarriages, and anencephaly. CASES: Fluorescence in situ hybridization
      techniques were used in the diagnosis of steroid sulfatase deficiency prenatally
      in three cases with low or undetectable unconjugated E3 levels. Results showed a
      male fetus with a deleted steroid sulfatase region, but intact Kallmann syndrome
      region in all three cases. One mother was studied by fluorescence in situ
      hybridization and showed a similar deletion for steroid sulfatase gene in one
      copy of X chromosome (carrier). CONCLUSION: Women with undetectable or very low
      levels of estriol on serum screening should be counseled regarding steroid
      sulfatase deficiency with evaluation by fluorescence in situ hybridization.

PMID- 9764666
TI  - A new therapeutic approach to the fetus with congenital complete heart block:
      preemptive, targeted therapy with dexamethasone.
AB  - BACKGROUND: Therapy of established congenital complete heart block in the fetus
      has resulted in improved survival but persistence of heart block. This exposes
      the infant to the morbidity of heart block, including the risk of sudden death
      and pacemaker implantation. CASE: A 35-year-old gravida 2, para 1, with Sjogren
      syndrome and a previous pregnancy complicated by congenital complete heart block
      presented during her second pregnancy. Intensive fetal monitoring with
      echocardiography was employed. Early evidence of myocardial dysfunction and
      dysrhythmia was found, dexamethasone therapy was initiated, and the dysfunction
      and dysrhythmia resolved. The pregnancy went to term without further
      complication. CONCLUSION: This represents a new and successful strategy to
      identify very early signs of myocardial disease in a fetus at high risk of
      congenital complete heart block, enabling targeted, preemptive therapy.

PMID- 9764667
TI  - Magnesium sulfate, maternal hypothermia, and fetal bradycardia with loss of heart
      rate variability.
AB  - BACKGROUND: Fetal bradycardia and decreased heart rate variability can indicate a
      nonreassuring fetal status. However, there can be iatrogenic, physiologic, or
      pathologic causes. CASE: A patient in premature labor received toxic levels of
      magnesium sulfate for tocolysis. Elevated maternal serum magnesium levels
      correlated inversely with maternal temperature and both fetal heart rate and
      fetal heart rate variability. There was also a relative decrease of the maternal
      heart rate from baseline. When the magnesium levels returned to normal, these
      vital signs returned to normal. CONCLUSION: Magnesium sulfate therapy can result
      in maternal hypothermia and a decrease in fetal heart rate and heart rate
      variability. Maternal hypothermia might be the cause of fetal bradycardia. A
      direct action of magnesium on the fetal heart might be the cause of heart rate
      variability.

PMID- 9764668
TI  - Hysterotomy facilitation of the vaginal delivery of the posterior arm in a case
      of severe shoulder dystocia.
AB  - BACKGROUND: Shoulder dystocia is an obstetric emergency that can be resolved
      usually with one or a series of maneuvers performed vaginally. On rare occasions
      these maneuvers may fail, and the obstetrician must employ less familiar
      techniques to achieve delivery. CASE: A 30-year-old, gravida 6, developed a
      severe shoulder dystocia while delivering a 5970 g infant. Classical vaginal
      maneuvers failed due to the severity of the impaction. After general anesthesia
      was induced, additional maneuvers such as cephalic replacement and transabdominal
      rotation also failed. The dystocia was resolved ultimately by a transabdominally
      facilitated vaginal posterior arm delivery followed by transabdominal shoulder
      rotation and vaginal extraction. CONCLUSION: In catastrophic cases of shoulder
      dystocia, transabdominal performance or facilitation of traditional vaginal
      maneuvers may lead to resolution.

PMID- 9764669
TI  - Cesarean delivery of twins during maternal cardiopulmonary arrest.
AB  - BACKGROUND: In modern times, maternal death is rare. Timely cesarean delivery in
      the setting of maternal cardiopulmonary arrest may save both the infant and the
      mother. CASE: A 36-year-old white woman with a twin pregnancy suffered
      cardiopulmonary arrest at 28 weeks' gestation. Advanced cardiopulmonary
      resuscitative measures were unsuccessful, and the twins were delivered by
      cesarean at the bedside. Immediately after delivery, a maternal pulse was noted;
      both the mother and her infants are alive 15 months later. CONCLUSION: Relieving
      vena caval occlusion by perimortem cesarean delivery in a term gravida allows
      chest compressions to provide sufficient cardiac output in the unfortunate event
      of maternal cardiopulmonary arrest. When delivery occurs within 5 minutes of
      maternal insult, the neonatal outcome is favorable.

PMID- 9764670
TI  - Postpartum renal failure: a complex case with probable coexistence of hemolysis,
      elevated liver enzymes, low platelet count, and hemolytic uremic syndrome.
AB  - BACKGROUND: Postpartum renal failure in previously healthy subjects is associated
      most often with preeclampsia and/or hypertension; hemolysis, elevated liver
      enzymes, low platelets (HELLP) syndrome, hemolytic uremic syndrome; or thrombotic
      thrombocytopenic purpura. Transient oliguria associated with preeclampsia is
      common, but renal failure is rare. Coexistence of HELLP and hemolytic uremic
      syndromes has been suggested, but histopathologic documentation of this
      combination has been scarce. CASE: A 30-year-old primigravida with severe
      preeclampsia at 35 weeks and 3 days' gestation presented with the development of
      HELLP syndrome and renal failure postpartum. Histopathologic lesions
      characteristic of hemolytic uremic syndrome were present in the kidney.
      CONCLUSION: Probable overlapping of HELLP and hemolytic uremic syndromes in
      pregnancy or postpartum should be taken into consideration when treating patients
      with these syndromes and associated complications, such as renal failure.

PMID- 9764671
TI  - Hypereosinophilic syndrome in a trisomy 21 fetus.
AB  - BACKGROUND: Hypereosinophilic syndrome is characterized by peripheral blood
      eosinophilia and multiple organ system involvement. Only one case in a newborn
      has been reported. CASE: Fetal sonography performed on a 33-year-old woman at 35
      weeks' gestation showed pericardial effusion and cardiomegaly. The infant was
      delivered by cesarean at 35 weeks' gestation because of a worsening of the
      pericardial effusion. Hematologic studies revealed unexplained hypereosinophilia,
      and the pericardial fluid contained a large number of eosinophils. Chromosomal
      analysis revealed trisomy 21. The hypereosinophilia, pericardial effusion, and
      cardiomegaly all resolved after 8 weeks of steroid therapy. CONCLUSION:
      Hypereosinophilic syndrome caused pericardial effusion and cardiomegaly in a
      fetus with trisomy 21.

PMID- 9764672
TI  - Postmortem DNA diagnosis of factor V Leiden in a neonate with systemic thrombosis
      and probable antithrombin deficiency.
AB  - BACKGROUND: Spontaneous neonatal thrombosis due to heritable gene defects has
      been reported in the past. A recently discovered defect, the factor V Leiden
      mutation, is the most frequent inherited risk factor for venous thrombosis. CASE:
      Factor V Leiden was diagnosed postmortem in a neonate who died from complications
      of vena caval and aortic thrombosis. Investigation into the family history
      revealed that the father had a record of multiple thromboses, and blood testing
      demonstrated that the father had antithrombin deficiency and the mother was
      heterozygous for factor V Leiden. Although we were unable to demonstrate directly
      the presence of antithrombin deficiency in the infant, we propose that a
      combination of the two inherited disorders was likely the cause of fatal neonatal
      thrombosis. CONCLUSION: The present report highlights the importance of a
      complete prenatal genetic analysis, including factor V Leiden testing and
      antithrombin measurement in families with a history of thrombotic disorders.

PMID- 9764673
TI  - Etretinate: therapy for plasma cell vulvitis.

PMID- 9764674
TI  - Deep vein thrombosis in patients with large uterine myomata.

PMID- 9764675
TI  - A carcinoid tumor of the broad ligament.

PMID- 9764676
TI  - Abdominal tuberculosis mimicking metastatic ovarian carcinoma.

PMID- 9764677
TI  - Delayed retained products of conception after second-trimester abortion.

PMID- 9764679
TI  - Transfusion issues in a gravida with sickle cell disease.

PMID- 9764678
TI  - Successful pregnancy in an adolescent with perinatally acquired human
      immunodeficiency virus.

PMID- 9764680
TI  - Marfan syndrome, aortic dilatation, and pregnancy.

PMID- 9764681
TI  - Fetal triploidy: a unique cause of the stuck twin sign.

PMID- 9764682
TI  - Intrauterine Listeria infection of the nonpresenting twin.

PMID- 9764683
TI  - Conjoined twins in a triplet pregnancy.

PMID- 9764684
TI  - Breast engorgement and lactation associated with thyrotropin-releasing hormone
      administration.

PMID- 9764685
TI  - Resolution of fetal tachycardia and hydrops by a single adenosine administration.

PMID- 9764686
TI  - Placental abruption and fetal death with airbag deployment in a motor vehicle
      accident.

PMID- 9764687
TI  - Surgical debridement of necrotizing endomyometritis after cesarean delivery.

PMID- 9764688
TI  - Disseminated neonatal herpes infection.

PMID- 9764689
TI  - Meta-analysis of estrogen therapy in the management of urogenital atrophy in
      postmenopausal women: second report of the Hormones and Urogenital Therapy
      Committee.
AB  - OBJECTIVE: To evaluate the efficacy of estrogen therapy in the treatment of
      postmenopausal women with symptoms and signs associated with urogenital atrophy,
      by meta-analysis of available data. METHODS: We searched the literature (Excerpta
      Medica, Biosis, MEDLINE, and hand search) for studies published between January
      1969 and April 1995. Criteria for inclusion were English-language articles, peer
      reviewed original publications, and urogenital atrophy assessed by at least one
      of the following outcomes: patient symptoms, physician report, pH, or cytologic
      change. Data had to allow comparison between treated and control groups in
      controlled trials or an estimated change from baseline in uncontrolled series.
      Meta-analytic methods were applied separately to controlled clinical trials and
      uncontrolled studies. RESULTS: Of the 77 relevant articles reviewed, nine
      contained ten randomized controlled trials. Meta-analysis of these using the
      Stouffer method revealed a statistically significant benefit of estrogen therapy
      for all outcomes studied. In 54 uncontrolled case series, the patient symptoms
      were treated by 24 different treatment modalities. All routes of administration
      appeared to be effective and maximum benefit was obtained between 1 and 3 months
      after the start of treatment. As expected, the least systemic absorption of
      estrogen was seen with estriol (administered orally or vaginally), then vaginal
      estradiol as measured by pretherapy and posttherapy serum estradiol and estrone.
      CONCLUSION: Estrogen is efficacious in the treatment of urogenital atrophy and
      low-dose vaginal estradiol preparations are as effective as systemic estrogen
      therapy in the treatment of urogenital atrophy in postmenopausal women.

PMID- 9764690
TI  - Natural history of cervical squamous intraepithelial lesions: a meta-analysis.
AB  - OBJECTIVE: To define the strengths and weaknesses of existing research on the
      natural history of cervical squamous intraepithelial lesions (SIL) and to
      estimate rates of progression and regression without treatment. DATA SOURCES:
      Studies of women whose cervical smears showed squamous atypia or worse and who
      were observed for a minimum of 6 months were identified by a search of MEDLINE
      from 1966 to 1996, Current Contents, the Federal Research in Progress database,
      and references of review articles and identified studies, and by experts in the
      field. METHODS OF STUDY SELECTION: Fifteen of 81 studies were eligible for data
      extraction. To be eligible, studies had to report a minimum of 6 months' follow
      up without treatment; relate entry cytologic findings to outcomes; and report
      entry cytologic findings so that the study population could be stratified into
      categories of atypical cells of undetermined significance (ASCUS), low-grade SIL,
      or high-grade SIL. Studies published before 1970 were excluded. TABULATION,
      INTEGRATION, AND RESULTS: Eligible studies, representing 27,929 patients, were
      stratified according to entry cytologic findings. The following rates of
      progression to high-grade SIL at 24 months were found: ASCUS, 7.13% (95%
      confidence interval [CI] 0.8%, 13.5%); low-grade SIL, 20.81% (6.08%, 35.55%); and
      high-grade SIL, 23.37% (12.82%, 32.92%). The following rates of invasive cancer
      at 24 months were found: ASCUS, 0.25% (0%, 2.25%); low-grade SIL, 0.15% (0%,
      0.71%); and high-grade SIL, 1.44% (0%, 3.95%). The following rates of regression
      to normal were found: ASCUS, 68.19% (57.51%, 78.86%); low-grade SIL, 47.39%
      (35.92%, 58.86%); and high-grade SIL, 35.03% (16.57%, 53.49%). Study
      heterogeneity was not explained by regression analysis of study level variables.
      CONCLUSION: Our findings for borderline and low-grade abnormal cervical cytologic
      results suggest a relatively low risk of invasive cervical cancer with
      observation up to 24 months and support the clinical policy of early colposcopy
      for high-grade lesions.

PMID- 9764691
TI  - Safety and durability of single-layer, stentless, biliary-enteric anastomosis.
AB  - Biliary-enteric anastomosis has long been associated with significant
      complications of early bile leak, cholangitis, and late stricture formation, and
      controversy exists regarding which operative technique best prevents these
      problems. Biliary-enteric anastomosis was performed using a single-layer running
      4-0 polyglactin (Vicryl) suture, without a transanastomotic stent, in 97 patients
      by a single surgeon over a 17-year period. Indications for operation included
      malignant obstruction (84.5%), benign stricture, choledocholithiasis, and
      choledochal cyst. The most common operation performed was a
      choledochoduodenostomy; the remaining operations were either Roux-en-Y
      choledochojejunostomy, hepaticoduodenostomy, or Roux-en-Y hepaticojejunostomy.
      Complications occurred in 14.1 per cent of patients; there was one perioperative
      death. There was only one case of anastomotic leak (1%), which resolved
      spontaneously within 1 week. Mean hospital stay was 8.7 days. The mean follow-up
      was 13.1 months in all patients. Among patients with benign disorders of the
      biliary tract, the mean follow-up was 21 months, during which time no patient
      developed an anastomotic stricture. One patient experienced postoperative
      cholangitis, although not as a result of anastomotic stricture. Biliary-enteric
      anastomosis for both benign and malignant disorders can be safely performed using
      a running, absorbable suture without a stent.

PMID- 9764692
TI  - Prognosis and treatment of bile duct carcinoma.
AB  - Bile duct carcinomas present a therapeutic challenge because of different
      histologies, tumor locations, and resectabilities. The goal of our study was to
      identify prognostic factors to better delineate therapeutic options. Forty
      patients (30 males and 10 females) diagnosed with bile duct cancer, treated
      between 1985 and 1996, at Kaiser Permanente Medical Center, Los Angeles were
      retrospectively reviewed. Three prognostically significant variables were
      identified: tumor histology, tumor location, and resection. Papillary histology
      was the most significant determinant of long-term survival. Of six patients with
      papillary adenocarcinoma, four patients (67%) underwent resection, with all four
      achieving long-term survival. Lower-third lesions also demonstrated a survival
      advantage. Four out of 12 (33%) lower-third tumors were resected, with a median
      survival of 36 months. Irrespective of tumor histology or tumor location, tumor
      resection always afforded longer survival times than did palliative treatments. A
      prognostic classification system based on weighted values of significant
      variables is presented that accurately predicted long-term survival. In
      conclusion, bile duct tumors in general are incurable, except perhaps for a small
      subset of patients with papillary adenocarcinoma. Papillary histology is the most
      significant determinant of ultimate survival and cure. A multifunctional
      prognostic classification system can be helpful for this perplexing disease.

PMID- 9764693
TI  - Outcomes from nonemergent orthotopic liver transplantation: is postoperative care
      becoming routine?
AB  - The outcome of surgical intensive care unit (SICU) care after nonemergent
      orthotopic liver transplantation (OLTX) was evaluated in 168 consecutive patients
      over a 6-year period (1/90-12/95). Prospective data collected included age, first
      and last SICU day Simplified Acute Physiology Score and Quantitative Therapeutic
      Intervention System Score, SICU length of stay (LOS), and mortality. The patient
      population was 61 per cent male and 39 per cent female, with ages ranging from 20
      to 75 years. A total of four patients died in the SICU, for a mortality of 2.4
      per cent. Over the study period, SICU LOS decreased by 21 per cent, from 3.9 +/-
      0.7 to 3.1 +/- 0.3 days (P < 0.05). Although no difference in admission severity
      of illness was observed over the study period, there was an increase in the
      intensity of intervention performed on admission to the SICU. Over the study
      period, there was no difference in severity of illness or intensity of
      intervention upon discharge to floor care. The decreased SICU LOS did not
      adversely affect patient mortality or severity of illness upon SICU discharge
      during the 6-year period. With intensified SICU intervention, nonemergent
      orthotopic liver transplantation patients can have a shorter SICU LOS without
      adverse effects on outcome.

PMID- 9764694
TI  - Gastric cancer: three decades of surgical management.
AB  - Hospital records of all 277 patients who underwent surgery for gastric
      adenocarcinoma at the University of California at Los Angeles Medical Center from
      1970 through 1996 were reviewed. Patients were stratified into three groups
      comprising 1970 to 1979, 1980 to 1989, and 1990 to 1996. The incidence of stage
      IV disease decreased by 50 per cent over the course of the study (P < 0.001).
      Lymph node involvement declined by 30 per cent (P < 0.01). Endoscopy displaced
      contrast radiography as the primary diagnostic modality. Sensitivity of
      endoscopic biopsy averaged 92 per cent. Twice as many patients were resected for
      cure in the current decade compared with the 1970s (P < 0.001). Operative
      mortality was less than 2.5 per cent for the entire period studied and has been
      nil in the 1990s. Intraoperative blood loss and transfusion requirements also
      decreased significantly each decade. Hospital stay was shortened by 41 per cent
      and the length of postoperative stay in the intensive care unit decreased from a
      median of 4 days to zero. Five-year survival improved significantly during the
      study period, mirrored by an increase in survival for early cancers. We have
      found an earlier presentation of gastric adenocarcinoma over the past 3 decades
      that parallels an increased use of endoscopy and an improved sensitivity of
      endoscopic biopsy. More patients are now resectable than in previous decades.
      Survival after surgical treatment of gastric adenocarcinoma improved between 1970
      and 1996, partially due to an increase in earlier stage lesions. Improved
      survival is also demonstrable when only early stage cancers are considered.

PMID- 9764695
TI  - Ultrasound characteristics of breast carcinoma.
AB  - Recent advances in ultrasound technology, such as the use of high-frequency
      linear transducers, color flow Doppler, and computer-enhanced imaging, have
      improved the diagnostic utility of ultrasound. The following retrospective study
      was performed to evaluate the efficacy of sonographic signs of malignancy and to
      compare sonography to mammography in 157 patients with palpable, biopsy-proven
      breast carcinomas. The mammogram reports and sonograms were all reviewed. The
      grade of each mammogram was recorded using the American College of Radiology
      mammogram grading scale. All sonograms were reviewed and assigned a score using
      an adaptation of this scale. Of 157 lesions, 121 were read as suspicious or
      probable malignancies on mammogram. Thirty-three lesions were read as benign or
      normal on mammogram. Three patients did not receive mammograms. All 157 lesions
      were read as either suspicious or probably malignant on ultrasound. Using the 16
      described criteria, high-definition sonography complements mammography and
      appears to be a sensitive modality in the evaluation of palpable biopsy-proven
      breast malignancies. The diagnostic utility of ultrasound will likely be most
      important in the evaluation of nonpalpable breast masses; however, a prospective
      randomized trial will need to be performed.

PMID- 9764696
TI  - Two decades of cervical esophagostomy: indications and outcomes.
AB  - Diverting cervical esophagostomy is a surgical procedure generally reserved for
      extremely ill patients as a life-saving maneuver. However, it is also a procedure
      that is infrequently performed, such that most centers have limited experience
      with the operation. To investigate the indications and outcomes of cervical
      esophagostomy, we reviewed the use of this operation at UCLA Medical Center over
      the last 20 years as employed for esophageal leaks. Eighteen patients underwent
      this procedure for the following indications: leak with malignant
      tracheoesophageal fistula (11%), anastomotic leak (44%), endoscopic injury (18%),
      gunshot wound (5.5%), operative injury (11%), corrosive ingestion (11%), and
      spontaneous rupture (5.5%). Overall mortality directly attributable to sepsis was
      33 per cent. Of the surviving patients, 67 per cent later underwent
      reconstruction. Seventy-two per cent of patients had end esophagostomies, and the
      remainder had loop diversions. The primary indication for operation in these
      patients was persistent sepsis after initial surgical management of esophageal
      spillage into the mediastinum or neck. This series suggests that cervical
      esophagostomy, when applied to the appropriate patient population, can decrease
      mortality and allow subsequent alimentary reconstruction.

PMID- 9764697
TI  - Accelerated recovery after coronary artery bypass surgery in patients with poor
      left ventricular function: preliminary report.
AB  - The success of "fast-track" accelerated recovery pathways in improving patient
      outcomes after coronary artery bypass graft surgery (CABG) has prompted expanded
      application. Although initially used only in routine cases, higher-risk cohorts
      may also benefit from this collection of management techniques. Twenty-seven
      consecutive patients with ejection fractions (EFs) less than or equal to 30 per
      cent (group I) undergoing CABG requiring cardiopulmonary bypass were started on
      our routine care path. The results of this effort were retrospectively compared
      with 27 concurrent patients with an EF greater than or equal to 50 per cent
      (group II) undergoing CABG at our institution. Outcome criteria included
      postoperative extubation (by 6 hours), transfer from intensive care unit (in < or
      = 24 hours), and hospital discharge on or before postoperative day 5. As
      anticipated, group I patients deviated from pathway criteria more frequently than
      did group II. However, despite severely compromised preoperative cardiac
      function, 52 per cent of group I patients were extubated within the first 6 hours
      postoperatively, 51 per cent were discharged from the intensive care unit on the
      1st postoperative day, and 52 per cent were discharged from the hospital within
      the first 5 postoperative days. Group II patients' values for these parameters
      were 96, 96, and 70 per cent, respectively. No adverse effects could be
      attributed to pathway expectations. The results of this preliminary study suggest
      that accelerated care pathways may be safely applied to patients with severely
      low EFs and deserve further study.

PMID- 9764698
TI  - Molten metal burns: early treatment improves outcome.
AB  - Molten metal burns have received relatively little attention in the surgical
      literature. We performed a retrospective chart review of 150 patients who
      sustained molten metal burns between 1972 and 1997. The injuries all occurred in
      male foundry workers, most commonly from molten aluminum (60%). The typical
      accident was that of a splatter spill, creating a full-thickness burn. The mean
      burn size was 2.3 per cent of the body surface area (range, 0.25-25%). The lower
      extremities were the most commonly injured areas (85%), yet 37 per cent of
      patients had multiple sites burned. Patients were often initially treated
      nonoperatively and then referred to a surgeon when the wound failed to heal.
      Hospitalization was necessary in 89 patients at a mean of 16 days after the
      injury, and 92 patients required an operation, most commonly excision of the
      wound with skin grafting. The mean length of hospital stay was 11.2 days, and
      mean absence from work was 72.6 days. Fifty-one patients treated by the burn
      surgeon within 2 weeks of injury had a mean length of disability significantly
      shorter than those referred late (53.5 vs. 83.4 days; P < 0.05). We believe that
      an underestimation of the severity of these burns often leads to a delay in
      correct therapy and extends disability.

PMID- 9764700
TI  - Laparoscopic management of acute cholecystitis with subtotal cholecystectomy.
AB  - Approximately 20 per cent of laparoscopic cholecystectomies performed for acute
      cholecystitis require conversion to open cholecystectomy because of severe
      inflammation. In a retrospective review of 125 consecutive patients undergoing
      laparoscopic surgery for gallbladder disease from January 1995 through June 1997,
      31 had acute cholecystitis. Eight patients underwent a subtotal cholecystectomy
      because of severe inflammation. There were no conversions to open cholecystectomy
      and no intraoperative complications. Selected patients were evaluated and treated
      for common duct stones with preoperative endoscopy to avoid intraoperative
      cholangiography. One patient had a retained common duct stone successfully
      managed with postoperative endoscopy. Laparoscopic subtotal cholecystectomy is a
      safe and effective alternative to conversion to open cholecystectomy for severe
      inflammation associated with acute cholecystitis. Endoscopic assessment and
      treatment of common duct stones when indicated either before or after surgery
      omits the use of intraoperative cholangiography and potential injury to the
      inflamed ducts.

PMID- 9764699
TI  - Epidemiology of immediate and early trauma deaths at an urban Level I trauma
      center.
AB  - The objective of this study is to identify and differentiate the injury patterns
      and causes of death among patients who died within the 1st hour and those in the
      period between 1 and 48 hours after hospital admission. Information was collected
      from the 1994 to 1996 trauma data base at an urban Level I trauma center. The
      records of 155 trauma patients who died within the 1st hour (immediate trauma
      death, ITD) and between 1 and 48 hours (early trauma death, ETD) were examined
      retrospectively. Total and constituent Injury Severity Score (ISS), Trauma Score
      (TS), and Glasgow Coma Score were analyzed. ITDs constituted 49 per cent of all
      deaths within 48 hours. Blunt mechanisms accounted for 37 per cent of ITDs and 40
      per cent of ETDs (not significant), whereas penetrating trauma accounted for 59
      per cent of ITDs and 56 per cent of ETDs (not significant). Exsanguination most
      commonly caused death among ITDs (54%) and head injury (51%) among ETDs (P <
      0.01). Patients who died within the 1st hour had higher ISS (42.6 +/- 23.2, P <
      0.03), lower TS (1.7 +/- 1.9, P < 0.0001), and lower Glasgow Coma Score (3.1 +/-
      1.1, P < 0.0001) than those who died after the 1st hour. Patients with ITD had a
      significantly worse chest ISS than those with ETD (47.4 +/- 28.6 vs 19.0 +/-
      19.1, P < 0.0001). We conclude that 1) ITD is caused primarily by exsanguination,
      whereas ETD is largely due to the sequelae of severe neurologic injury; 2) ITD
      has a significantly lower TS and higher ISS than ETD; and 3) thoracic injuries
      are more severe among patients with ITDs than among those with ETDs. The severity
      of thoracic injury among ITDs suggests that rapid surgical intervention is
      critical during the resuscitation of these severely injured patients.

PMID- 9764701
TI  - Use of rectal cancer position as a prognostic indicator.
AB  - The hypothesis of this study was that the position of rectal cancer within the
      circumference of the rectum influences mortality. Tumor position was
      prospectively documented in 181 patients with rectal carcinoma by two examiners.
      The results were analyzed for correlation to survival using the Lifetest model
      and for multivariate correlation using the Cox regression model. An anterior
      tumor location was present in 43 patients and was found to have a significantly
      higher survival rate than other positions. Two-thirds of anterior tumors were of
      pathologically favorable Dukes' stages. Fifty-five patients had posterior tumors
      with decreased survival rates, two-thirds of which were of unfavorable stages.
      Circumferential position in 61 patients was most predictive of poorer outcome,
      with a relative risk of death being increased by 4.6 times (P = 0.014) and a 5
      year survival rate of 68.8 per cent; 85 per cent of these tumors were of
      pathologically unfavorable stages. The 5-year survival rate for the whole group,
      which included 181 patients with all histopathological stages except those with
      distant metastases at presentation, was 78.5 per cent. This ranking of survival
      rates was found to be consistent in each category with the postoperatively
      determined Dukes' stage, which carried a prognostic significance of P = 0.0001.
      We conclude that tumor position is a significant indicator of prognosis available
      before surgery for rectal cancer.

PMID- 9764703
TI  - Herniography: a review of 333 herniograms.
AB  - We reviewed 333 consecutive herniographic studies in 306 patients for whom
      clinical data were available. Symptoms with either a negative or inconclusive
      physical examination (PE) were the most frequent reasons for requesting a
      herniogram. The herniogram was found to be more sensitive for the diagnosis of
      hernia, particularly inguinal, than PE. In 56 of 57 patients who came to
      operation the herniogram and the PE were concordant. In one patient, an
      incisional hernia was found at operation that had not been appreciated as such on
      the herniogram. We believe herniography should be used more frequently when the
      diagnosis of hernia is uncertain on PE, thereby reducing the incidence of
      unnecessary operative procedures.

PMID- 9764702
TI  - Topical nitroglycerin in the management of anal fissure: an explosive outcome!
AB  - Anal sphincter spasm is a common finding in patients with anal fissure disease.
      It is postulated that spasm impedes mucosal blood flow and impairs healing.
      Topical nitroglycerin (NTG), a nitric oxide donor compound, has been shown to
      cause relaxation of the anal sphincter and may have treatment efficacy in the
      management of anal fissure. The purpose of this study was to assess the
      usefulness of NTG for anal fissure. We performed a retrospective review of
      patients with anal fissure treated with various concentrations of topical NTG
      ointments over an 18-month period ending July 1997. Of the 81 patients studied,
      44 (54%) were male. There were 42 acute and 39 chronic fissures. NTG preparations
      included 1 per cent isosorbide (n = 37), 0.2 per cent NTG (n = 38), and 0.5 per
      cent NTG (n = 6). Healing with NTG therapy occurred in 29 acute (69%) and 21
      chronic fissure (54%) patients. There was no difference in the incidence of
      healing of acute or chronic fissure between the various NTG treatment preparation
      groups. When acute and chronic fissure therapy was subdivided by time of NTG
      treatment (immediate versus post-conservative therapy failure (PCF)), 14 (74%) of
      acute PCF and 5 (42%) of chronic PCF patients healed. We conclude that no single
      formula was superior. When patients were subdivided into a PCF group, NTG therapy
      demonstrated a significant salvage rate, thus avoiding surgery.

PMID- 9764704
TI  - Perforated appendicitis: is it truly a surgical urgency?
AB  - Advanced perforated appendicitis with localized findings has classically been
      treated with either operative therapy or with percutaneous drainage. The role of
      nonoperative therapy followed by interval appendectomy (IA) remains
      controversial. We assessed the safety and efficacy of conservative management for
      perforated appendicitis in a 5-year review of patients treated conservatively for
      perforated appendicitis with localized abscess or phlegmon. Patients were treated
      initially with intravenous antibiotics, and CT-guided drainage was used only if
      the patient failed to improve after 48 to 72 hours. Patients still not improving
      underwent appendectomy. Patients responding to conservative therapy were
      recommended IA in 6 to 12 weeks. Sixty-six patients with 54 abscesses and 10
      phlegmons were treated. Fifty-one patients (92%) improved without surgery. Only
      58 per cent of the abscesses required percutaneous drainage. The mean length of
      stay for conservative therapy was 7.6 days. Forty-one patients underwent IA with
      a 10 per cent morbidity and a mean length of stay of 1.4 days. Conservative
      management of appendicitis with localized perforation or phlegmon is safe and
      effective. Percutaneous drainage is frequently not required. IA is associated
      with low morbidity without prolonged hospitalization.

PMID- 9764705
TI  - Laparoscopy identifies unexpected groin hernias.
AB  - Diagnostic laparoscopy performed before laparoscopic repair of groin hernias
      offers an opportunity to examine all hernial orifices. This study was undertaken
      to evaluate the accuracy of the preoperative clinical diagnoses and to determine
      the frequency of unexpected groin hernias. Between December 1990 and November
      1997, 253 patients (243 male) underwent laparoscopic repair of 560 hernias. The
      total extraperitoneal technique was used in 93 per cent of the cases. Diagnostic
      laparoscopy was performed before and after the preperitoneal dissection and
      repair. Preoperatively, hernias were thought to be unilateral in 73 patients
      (Group A) and bilateral in 180 patients (Group B). Incorrect diagnoses in 50 of
      73 patients (68%) thought to have unilateral hernias included bilateral hernias
      in 37 patients (50%), a different type of ipsilateral inguinal hernia in 7
      patients (10%), or a femoral hernia in 6 patients (8%). Incorrect diagnoses in 91
      of 180 patients (50%) thought to have bilateral hernias included a different
      and/or additional type of ipsilateral inguinal hernia on either side in 63
      patients (35%), a femoral hernia in 21 patients (12%), or a unilateral hernia in
      7 patients (4%). Unexpected hernias that would not have been treated with an
      anterior approach were found in 64 patients (25%; 27 were femoral and 37 were
      contralateral). The laparoscopic technique allows for identification and repair
      of previously undiagnosed contralateral and femoral hernias at the first
      operation.

PMID- 9764707
TI  - White blood cell count is a poor predictor of severity of disease in the
      diagnosis of appendicitis.
AB  - The white blood cell (WBC) count is considered to be a useful test in the
      diagnosis of appendicitis. The purpose of this study was to examine the clinical
      features of patients with normal WBC appendicitis and also to determine whether a
      higher WBC count correlates with a more advanced stage of appendicitis. Patients
      with pathologically confirmed appendicitis from January 1989 to December 1994
      were included in the study (n = 1919). The age, gender, temperature, length of
      hospital stay, and severity of disease (1 = acute appendicitis; 2 = gangrenous
      appendicitis; 3 = perforated appendicitis with abscess formation; 4 =
      appendicitis with diffuse peritonitis) were compared for patients with a normal
      WBC count (range, 3.8-10.9) versus those who had an elevated WBC count. A normal
      WBC count was seen in 11 per cent of patients (n = 209). There was no difference
      in age, temperature, gender, or severity of disease in the patients with a normal
      WBC count compared with those with an elevated WBC count (P > 0.05). The severity
      of disease of patients with a normal WBC count were: 1 = 58 per cent; 2 = 13 per
      cent; 3 = 7 per cent; and 4 = 22 per cent. For patients with an elevated WBC
      count the scores were: 1 = 57 per cent; 2 = 17 per cent; 3 = 13 per cent; and 4 =
      14 per cent. The proportion of gangrenous and perforated appendicitis in the
      patients with a normal WBC count is the same as in the patients with an elevated
      WBC count.

PMID- 9764706
TI  - Diverting loop versus end ileostomy during ileoanal pullthrough procedure for
      ulcerative colitis.
AB  - A two-stage ileoanal pullthrough procedure (IAPP) is often used for patients with
      ulcerative colitis (UC) requiring proctocolectomy. We analyzed the recent
      University of California at Los Angeles experience with diverting end and loop
      ileostomies in patients undergoing a two-stage IAPP. A retrospective analysis of
      21 patients with UC undergoing loop ileostomy between March 1992 and March 1995
      was performed. Comparison was made with 21 age- and gender-matched patients
      undergoing end ileostomy between January 1991 and December 1995. There was no
      mortality or major septic complications. A second laparotomy was required in all
      patients with end ileostomies, whereas loop ileostomies were closed without
      abdominal exploration. During ileostomy closure, operative time and mean hospital
      stay were significantly reduced with the use of loop ileostomy. The time to oral
      feeding was not significantly different between end and loop ileostomy groups
      after ileostomy closure. The complication rate after IAPP was similar between
      groups. However, after ileostomy closure, the complication rate was significantly
      reduced with the use of loop ileostomy. We conclude that loop ileostomy is a
      desirable option for UC patients undergoing intestinal diversion during IAPP.
      Loop ileostomies can be created easily and without an increase in operative time.
      Subsequent ileostomy closure can be performed as a local procedure, which may
      shorten operative time and length of hospital stay.

PMID- 9764708
TI  - Colonic stents in colorectal obstruction.
AB  - Obstruction is the presenting symptom of colorectal cancer in up to 40 per cent
      of patients. Benign strictures and other neoplasms including lymphoma and
      gynecologic tumors occur as well. Emergent operative therapy is often suboptimal
      and associated with significant morbidity and mortality. Our objective was to
      review our experience with stent placement for colonic obstruction. Seven
      patients underwent stent placement for a total of eight procedures. There were
      three patients with unresectable colorectal cancer, two patients with metastatic
      gynecologic cancer, one patient with rectal lymphoma, and one patient with
      metastatic cancer of unknown primary. All colonic stents were Wallstents placed
      by the same endoscopist under fluoroscopic and endoscopic guidance. Stents were
      successfully placed in all patients without complication. One patient underwent
      placement of two stents in succession for a long stenosis. Six of seven patients
      (86%) had resolution of the obstruction and return of bowel function. Five of
      seven were tolerating a diet within 24 hours. One patient's mental status did not
      allow for oral intake. Four patients were discharged within 48 hours. Two
      patients died within the same hospitalization as a result of metastatic disease.
      One patient was found to have multilevel disease requiring stoma placement. There
      was no morbidity or mortality associated with stent placement, and 86 per cent of
      patients had palliation of the obstruction. We conclude that colonic stent
      placement is a safe and effective therapy for colorectal obstruction at this
      institution.

PMID- 9764709
TI  - The use of technetium-labeled erythrocyte scintigraphy in the evaluation and
      treatment of lower gastrointestinal hemorrhage.
AB  - The percentage of incorrect operations performed as a result of technetium
      labeled erythrocyte scintigraphy has been reported as high as 42 per cent. Recent
      studies have found scintigraphy to be superior to angiography and propose that it
      be used as the primary diagnostic test in patients with lower gastrointestinal
      (GI) bleeding. A retrospective analysis was conducted of 105 patients with the
      symptoms of lower GI hemorrhage to determine the effect of erythrocyte
      scintigraphy on surgical management. Operative and pathology results were
      analyzed to determine the accuracy of the scintigraphy for localization of the
      bleeding source. In addition to tagged erythrocyte scans, 95 of 105 patients had
      additional diagnostic procedures: colonoscopy (78), upper endoscopy (47), and
      angiography (9). Scintigraphy localized a site of bleeding in 42 patients (colon,
      29; jejunum/ileum, 10; duodenum, 2; esophagus, 1). Surgical intervention was
      required in 25 patients, and the site of bleeding was correctly determined by
      scintigraphy in 22 of these patients (88%). The scans were negative in two
      patients, and the bleeding site was incorrectly reported in another. The patients
      who had operations were significantly more likely to have positive scintigraphy
      than the nonoperative group (P < 0.05). Preoperative localization of GI
      hemorrhage is possible in most patients with technetium-labeled erythrocyte scans
      (88% of operative patients). When combined with other tests to exclude upper GI
      bleeding, scintigraphy is a reliable means of guiding surgical intervention.

PMID- 9764710
TI  - Combined carotid endarterectomy and coronary artery bypass grafting in
      asymptomatic carotid artery stenosis.
AB  - The role of combined carotid endarterectomy (CEA) and coronary artery bypass
      grafting (CABG) in patients with severe asymptomatic carotid artery disease and
      concurrent symptomatic coronary artery disease is controversial. The objective of
      this report is to investigate the safety of combined CEA/CABG. The medical
      records of 30 patients who underwent combined CEA/CABG for coexistent
      asymptomatic carotid and symptomatic coronary artery occlusive disease were
      reviewed. All patients were scheduled for either elective or urgent myocardial
      revascularization due to their symptomatic coronary artery disease. Color-flow
      duplex scanning identified internal carotid artery stenosis of 80 to 99 per cent
      in 28 patients (93%) and 50 to 79 per cent in 2 patients (7%). Seventeen patients
      (57%) were male. The mean age was 64 +/- 10 years (range, 42-84 years).
      Contralateral internal carotid artery occlusion was present in four patients.
      Severe left main coronary artery disease was present in 12 patients (40%) and 7
      patients (23%) had an ejection fraction of less than 50 per cent. There were no
      perioperative deaths or strokes. One patient suffered a myocardial infarction on
      postoperative day 1. This study demonstrates the safety of combined CEA/CABG for
      coexistent coronary and asymptomatic carotid disease. Using this surgical
      approach for critical coexistent disease may minimize the incidence of
      perioperative cerebrovascular complications in patients undergoing CABG.

PMID- 9764711
TI  - Carotid endarterectomy and abdominal aoritc aneurysm repair: are these reasonable
      treatments for patients over age 80?
AB  - Due to the aging of America, increased numbers of very elderly patients require
      peripheral vascular surgery. From April 1980 to November 1997, 191 patients age
      80 years or older had carotid endarterectomy (CEA) and/or abdominal aortic
      aneurysm (AAA) repair at Loma Linda University Medical Center. The total
      perioperative stroke and death rate in the CEA group was 2.9 per cent. Mean
      postoperative cumulative survival in this group was 8.4 years. The cumulative
      stroke-free survival rate was 95.5 per cent for all yearly postoperative
      intervals up to 12 years. The perioperative mortality rate was 10.7 per cent in
      the nonruptured AAA group and 53.8 per cent in the ruptured AAA group (P <
      0.00001). Mean cumulative survival was 8.6 years in the nonruptured AAA group and
      1.1 years in the ruptured AAA group (P = 0.0001). These data support the
      conclusion that CEA and nonemergent AAA repair in octo- and nonagenarians are
      safe and effective in prolonging stroke-free and rupture-free survival. The
      utility of ruptured AAA repair in this age-group is less clear.

PMID- 9764712
TI  - Wallgraft endoprosthesis: initial canine evaluation.
AB  - This study evaluated the in vivo deployment and the healing characteristics of a
      self-expanding endoluminal graft [Wallgraft (WG) Endoprosthesis] in a canine (n =
      22) aorta. The WG consisted of a 10 or 12 mm x 7.5 cm Wallstents (Schneider,
      Inc.) covered with polyethylene terephthalate (Dacron) graft material. Twenty-two
      WGs were deployed using fluoroscopic guidance. Devices were oversized
      approximately 10 per cent. Intravascular ultrasound (IVUS) was repeated, and
      balloon expansion along the length of the WG was performed to assure maximum
      expansion. WGs were evaluated with IVUS, angiography, and histology at 14 (n =
      4), 30 (n = 4), 90 (n = 4), 180 (n = 5), and 365 (n = 5) days. Predeployment
      aortic diameters were 9.9 +/- 1 mm. Mid-WG diameters were 9.0 +/- 0.8 mm before
      balloon dilation and 9.2 +/- 0.5 mm after dilation with 8- (n = 1), 10- (n = 16),
      and 12- (n = 5) mm balloons. Twenty-two of 23 devices were deployed accurately
      with good apposition and aortic flow after deployment. On explant, all of the
      covered grafts were widely patent on IVUS and angiogram. Four explants
      demonstrated gaps (due to WG taper) between the proximal or distal ends of the
      graft on IVUS. The device length (9.1 + 0.5 cm) did not change significantly
      after deployment. Histologically at 6 months and 1 year the lumens were cell
      lined. Scanning electron micrography demonstrated endothelial-like cells. This
      study demonstrates the ability of a WG to be accurately deployed and maintain
      excellent patency. Balloon expansion after deployment did not significantly
      increase the diameter. Clinical evaluation of this device is in progress.

PMID- 9764713
TI  - Surgical ligation of patent ductus arteriosus in very low birth weight infants:
      is it safe?
AB  - We evaluated the outcome of a combined medical and surgical treatment of patent
      ductus arteriosus (PDA) in newborns weighing less than 1500 g. Charts were
      retrospectively reviewed for 76 newborns with a PDA between 1993 and 1997.
      Thirteen infants had pre-existing conditions prohibiting the use of indomethacin;
      eight were managed surgically, five medically. The remaining 63 infants received
      indomethacin therapy. Thirty-two medical failures occurred, requiring surgical
      ligation of the PDA. Those requiring surgery had a lower average birth weight
      (847 versus 997 g) and gestational age (26 versus 28 weeks; P < 0.05).
      Indomethacin treatment was successful in 27 infants. There were only three
      operative complications: a small pneumothorax, wound bleeding, and a small aortic
      tear. All recovered uneventfully and no deaths were attributable to the surgical
      procedure itself. There was no difference in the incidence of respiratory
      distress syndrome, duration of intubation, sepsis, neonatal enterocolitis, renal
      dysfunction, bleeding disorders, or intraventricular hemorrhage among both
      groups. Surgical ligation of a PDA is associated with a high success rate, a low
      incidence of complications, and no additional morbidity than indomethacin alone.
      We propose that surgical ligation should be regarded as a first line therapy for
      very small premature infants who are at higher risk of medical failure.

PMID- 9764714
TI  - Lung volume reduction surgery: a cost and outcomes comparison of sternotomy
      versus thoracoscopy.
AB  - It remains unknown whether it is better to perform lung volume reduction surgery
      (LVRS) through video-assisted thoracoscopy (VATS) or sternotomy. This study
      compares both approaches in terms of surgical and patient outcomes as well as the
      associated costs. All patients undergoing LVRS from 1995 to 1997 at one
      institution by a single surgeon (PFW) were investigated. Preoperative,
      postoperative, and cost data were obtained from medical and financial records. A
      total of 42 patients with severe emphysema underwent LVRS (19 via sternotomy and
      23 via thoracoscopy). Both groups were comparable preoperatively. Comparison of
      intraoperative times revealed VATS takes longer to perform (sternotomy, 118 +/-
      29 minutes; thoracoscopy, 168 +/- 20 minutes). Postoperatively, the sternotomy
      patients had more days on the ventilator, more days in the intensive care unit,
      more days with an air leak, and longer hospital stays. In both groups, the
      majority of patients reported improvement in oxygen dependence as well as quality
      of life. Neither surgical approach conferred any long-term medical advantage;
      however, the average total hospital costs and charges were reduced in the VATS
      group (average cost: VATS, $27,178; sternotomy, $37,299). This study concludes
      that 1) LVRS seems to be beneficial for selected patients with end-stage
      emphysema; 2) postoperative morbidity and length of hospital stay are decreased
      in the VATS group; 3) long-term improvement in postoperative pulmonary function
      is not influenced by surgical approach; and 4) the overall charges and costs of
      the VATS approach is less than that of sternotomy.

PMID- 9764716
TI  - Clinical pathways for general surgeons: emergency small bowel resection.

PMID- 9764715
TI  - An early comparison between endoscopic ultrasound-guided fine-needle aspiration
      and mediastinoscopy for diagnosis of mediastinal malignancy.
AB  - Precise mediastinal lymph node staging is essential in non-small cell lung cancer
      for proper evaluation and treatment. In addition to CT, mediastinoscopy is
      routinely used for staging and diagnosis of mediastinal malignancy. Recently,
      endoscopic ultrasound (EUS) combined with fine-needle aspiration (FNA) biopsy has
      been used to evaluate mediastinal disease. The purpose of this study was to
      assess and compare mediastinoscopy with EUS/FNA in the evaluation of mediastinal
      masses. From August 1995 to July 1997, 21 patients with suspected mediastinal
      malignancy underwent cervical mediastinoscopy with biopsy. During this same
      period, seven patients with suspected mediastinal malignancy were evaluated using
      EUS/FNA. All patients were retrospectively studied. Both mediastinoscopy and
      EUS/FNA were highly sensitive in diagnosing mediastinal malignancy (100% and 86%,
      respectively). Specificity and positive predictive value were 100 per cent for
      both procedures. Mediastinoscopy and EUS/FNA are highly accurate methods of
      staging mediastinal malignancy. Mediastinoscopy provides better access to the
      upper and anterior mediastinum, whereas EUS/FNA can safely be used to biopsy
      subcarinal and posterior mediastinal masses. Mediastinoscopy and EUS/FNA target
      different areas of the mediastinum and may be complimentary in the evaluation of
      mediastinal malignancy and staging of bronchogenic carcinoma.

PMID- 9764717
TI  - Chronic sympathetic suppression in the treatment of chronic congestive heart
      failure.
AB  - Previous short-term studies demonstrated that treatment with clonidine produced
      significant hemodynamic improvement in patients with congestive heart failure
      (CHF). In this study we followed 12 CHF patients (10 M, 2 F age 63+/-11, 10 with
      ischemic cardiomyopathy and 2 with dilated cardiomyopathy) treated with 0.15 or
      0.075 mg oral clonidine twice daily for 13+/-5 months (range 6-23). with
      functional evaluation at baseline, 6 weeks and 6 months. There was suppression of
      circulating catecholamines, associated with significant ameliorations in NYHA
      class, in duration of exercise tolerance (from 246+/-68 sec to 362+/-30 and 459+/
      70 sec, respectively p < 0.02), in ejection fraction (from 32+/-7% to 35+/-5 and
      39+/-7% p < 0.04) and in left ventricular enlargement as assessed
      echocardiographically. There were also improvements in a number of
      electrophysiologic parameters calculated by computerized analysis of ambulatory
      ECG tapes, such as heart rate variability, indicating diminished propensity to
      malignant arrhythmias, as confirmed by decreases in the numbers of isolated
      premature ventricular contractions, couplets and episodes of non-sustained
      ventricular tachycardia. The data suggest that chronic central sympathetic
      suppression with clonidine in CHF results in significant functional amelioration
      and improved electrophysiologic stability.

PMID- 9764718
TI  - Dose-dependent reduction of myocardial infarct mass in rabbits by the NHE-1
      inhibitor cariporide (HOE 642).
AB  - The aim of this study was to investigate the dose-dependent effect of
      pretreatment with the selective sodium-hydrogen exchange NHE-subtype 1 inhibitor
      cariporide on myocardial infarct mass in a rabbit model of coronary ligation and
      reperfusion. Furthermore, in a second part of the study, we tested the effect of
      cariporide in the rabbits when given prior to reperfusion. Rabbits (n=49) were
      randomized in 7 groups: saline vehicle, cariporide: 0.01, 0.03, 0.1 and 0.3
      mg/kg, and subjected to a 30 min occlusion of a branch of the left coronary
      artery followed by 2 h reperfusion. Cariporide was given as a bolus intravenously
      10 min before occlusion or 5 min before reperfusion. After reperfusion,
      myocardial infarct mass was determined by triphenyl tetrazolium chloride staining
      and expressed as a percent of area at risk. Cariporide given intravenously 10 min
      before occlusion in doses of 0.01, 0.03, 0.1, 0.3 mg/kg, led to a dose-dependent
      reduction in infarct mass from 58+/-6% in controls to 48+/-4% (-17%, NS), 36+/-5%
      (-38%, p<0.05), 26+/-6% (-55%, p<0.05), 11+/-4% (-81%, p<0.05) respectively,
      whereas area at risk did not differ in between the groups. The effect of the
      lowest dose of 0.01 mg/kg did not reach significance. Plasma levels at different
      doses of cariporide were correlated to the respective infarct mass. After
      coronary occlusion left ventricular end-diastolic pressure (LVEDP) significantly
      increased throughout occlusion and reperfusion. Cariporide in the doses of 0.3,
      0.1 and 0.03 mg/kg normalized LVEDP when measured after 2 h reperfusion. In
      controls hemodynamic parameters such as mean arterial blood pressure (MAP), heart
      rate (HR), left ventricular pressure (LVP) and LV dP/dt(max) were not
      significantly changed by ischemia/reperfusion with the exception of MAP, LVP and
      LV dP/dt(max) which were significantly decreased after 120 min reperfusion.
      Cariporide at doses of 0.1, 0.03 and 0.01 mg/kg did not significantly influence
      these parameters, whereas the highest dose of 0.3 mg/kg prevented the decrease of
      MAP and LVP. Cariporide (0.3 mg/kg i.v.) administered 5 min before reperfusion
      significantly reduced infarct mass by 31%. Under these conditions the increase of
      LVEDP after coronary occlusion was not influenced by cariporide. As in the
      pretreatment experiments, the decrease of MAP and LVP was prevented when measured
      2 h after reperfusion. The results show that pretreatment with the NHE-subtype 1
      inhibitor cariporide is cardioprotective by reducing infarct mass in rabbits in a
      dose-dependent manner. While the cardioprotective effect of pretreatment could be
      demonstrated over a broad range of doses, the efficacy of the compound when given
      only on reperfusion was significant but more limited.

PMID- 9764719
TI  - Effect of the vasodilatory beta-blocker, nipradilol, and Ca-antagonist,
      barnidipine, on insulin sensitivity in patients with essential hypertension.
AB  - OBJECTIVES: To assess the effects of a vasodilatory beta-adrenoceptor blocker,
      nipradilol, and a long-acting Ca channel blocker, barnidipine, on insulin
      sensitivity. DESIGN: Insulin sensitivity was determined using a euglycemic
      hyperinsulinemic clamp technique before and after a 12-week treatment period in
      eighteen patients with essential hypertension. RESULTS: Both drugs decreased
      blood pressure without affecting any serum parameters of glucose and lipid
      metabolism. Nipradilol significantly augmented glucose infusion rate (GIR) from
      3.11+/-0.28 to 4.69+/-0.57mg/kg/min (p=0.027). Barnidipine also increased GIR
      from 3.91+/-0.43 to 5.29+/-0.43 mg/kg/min (p=0.028). Plasma norepinephrine
      concentrations significantly increased with barnidipine treatment, while
      nipradilol had no effect on plasma norepinephrine levels. No adverse events were
      reported during the study. CONCLUSIONS: These results suggest that vasodilatory
      beta-blockers such as nipradilol and long-acting Ca channel blockers such as
      barnidipine may be useful in the treatment of insulin resistant hypertensive
      patients.

PMID- 9764720
TI  - Comparative efficacies of a calcium antagonist and an alpha1 blocker in elderly
      hypertensive patients with stroke.
AB  - We compared the effects of nilvadipine, a calcium antagonist, and terazosin. an
      alpha1 blocker, on the hemodynamics and quality of life (QOL) in 12 elderly
      hypertensive patients with stroke. Following a washout period of 2 weeks.
      nilvadipine or terazosin was administered for 2 weeks in a randomized crossover
      manner. At the end of control and treatment periods, we measured the 24-hour
      ambulatory blood pressure (BP) and postural change of BP, and interviewed QOL.
      Terazosin treatment did not show consistent decrease of casual BP, but was
      associated with a transient decrease of systolic BP and an increase of pulse rate
      after standing, and enhanced postprandial decrease in BP. Nilvadipine decreased
      casual BP in a dose-dependent manner, but showed neither postural nor
      postprandial change of BP. There was no difference in QOL scores with either
      treatment. Results suggest that nilvadipine is preferable to terazosin for the
      treatment of elderly hypertensive patients with stroke.

PMID- 9764721
TI  - Protective effects of valsartan and benazeprilat in salt-loaded stroke-prone
      spontaneously hypertensive rats.
AB  - These experiments examined the effectiveness of chronic blockade of the renin
      angiotensin system with either valsartan or benazeprilat on survival, blood
      pressure and end-organ damage in salt-loaded stroke-prone SHR. Valsartan or
      benazeprilat given continuously by subcutaneous osmotic minipump beginning at
      10.5 weeks of age lowered blood pressure, as determined by radiotelemetry,
      prevented proteinuria, prolonged survival and decreased the severity of
      histopathological changes in the heart and kidney. These results indicate that
      angiotensin receptor blockade affords a similar degree of protection as
      inhibition of angiotensin converting enzyme in salt-loaded stroke-prone SHR.
      Furthermore, our results are consistent with a primary contribution of
      angiotensin II to the maintenance of blood pressure and support a principal role
      for angiotensin II-dependent mechanisms in the development of end-organ damage in
      the salt-loaded stroke-prone SHR.

PMID- 9764722
TI  - Hypertension development in Dahl S and R rats on high salt-low potassium diet:
      calcium, magnesium and sympathetic nervous system.
AB  - Dietary combination of high salt with low potassium (HSLK) exacerbates
      hypertension development in Dahl salt-sensitive (S) rats, and produces a mild
      degree of hypertension in otherwise salt-resistant (R) rats. Increased blood
      pressure in both strains is associated with increased urinary excretion of
      calcium and magnesium. The objective of this study was to determine the effect of
      blood pressure on body balance of these ions in Dahl rats on HSLK diet. Two
      groups of S and two groups of R weanlings were all placed on HSLK diet (NaCl=8%,
      K=0.2%) for eight weeks. One group of each strain was subjected to chemical
      sympathectomy with 6-hydroxydopamine (6-OHDA) to counteract hypertension
      development. Urinary norepinephrine was used to determine efficacy of 6-OHDA
      treatment. Systolic blood pressures of conscious animals were measured daily
      throughout the study. The last three days on the diet were used to determine
      total dietary intake and urinary as well as fecal excretion of sodium, calcium
      and magnesium. At the end of the study, extracellular fluid volume, serum
      aldosterone and parathyroid hormone were analyzed. Final systolic blood pressures
      in the 4 groups were as follows: S=235+/-9 mmHg (n=9); R=155+/-3 mmHg (n=8); 6
      OHDA S=151+/-6 mm Hg (n=8); 6-OHDA R=117+/-6 mm Hg. Chemical sympathectomy
      decreased blood pressure in both S and R rats. There was no indication of sodium
      accumulation in S rats. Associated with reduced parathyroid hormone levels the S
      strain had significantly less positive balance for calcium than the R strain,
      primarily due to increased urinary excretion. A less positive balance for
      magnesium was also observed, due mainly to relatively reduced intestinal
      absorption of the ion. We conclude that the HSLK diet is associated with
      inappropriate activation of the sympathetic nervous system and increased arterial
      pressure in both strains. In addition, since divalent cations may influence blood
      pressure, we suggest that the observed abnormalities in calcium and magnesium
      metabolism might independently promote hypertension development in the S strain.

PMID- 9764723
TI  - Development of monoclonal antibodies to erythroid progenitors in feline bone
      marrow.
AB  - Feline bone marrow cells can be enriched for erythroid and myeloid progenitors by
      counterflow centrifugal elutriation (CCE) and subsequent treatment of the CCE
      fractions with the soybean agglutinin (SBA) lectin. Separation of CCE fractions
      into SBA(-) and SBA(+) populations yielded cells enriched for BFU-E and CFU-GM
      progenitors, respectively. Differential analyses revealed a high percentage of
      erythroid lineage cells in the SBA(-) fractions and in the SBA(+) fractions a
      high concentration of myeloid cells of varying maturation stages. The latter
      cells, but not the CFU-GM progenitors, could be removed by immunomagnetic
      depletion from CCE fractions using a monoclonal antibody (MAb) specific for CD13
      cells in feline bone marrow, resulting also in a population containing
      predominantly erythroid differentiating cells. Mice were immunized with CCE
      fractions enriched for erythroid lineage cells and the splenocytes fused with
      SP2/O cells for hybridoma development. Supernatant culture fluids from 400
      hybridomas were analyzed by flow cytometry with whole bone marrow and select
      CCE/SBA fractions as the target cells. Those hybridomas suggestive of containing
      the desired antibodies as indicated by the percentage staining were subcloned and
      the MAbs utilized in clonogenic assays. Treatment of bone marrow cells or CCE
      fractions with the MAbs followed by immunomagnetic depletions led to
      identification of two, K-1 and Q-3, reactive with the BFU-E progenitor and one, K
      7, reactive only with late-differentiating erythroid lineage cells. Thus, removal
      of cells from a CCE/SBA suspension reactive with K-1 or Q-3 led to greater than
      80% reductions of the BFU-E progenitors and a population enriched for CFU-GM.
      Removal of cells reactive with MAb K-7, however, led to a marked enrichment, 5-8
      fold, of both BFU-E and CFU-GM progenitors.

PMID- 9764724
TI  - Interactions between lipopolysaccharides and blood factors on the stimulation of
      equine polymorphonuclear neutrophils.
AB  - In horses, the mechanisms of lipopolysaccharide (LPS) stimulation of isolated
      neutrophils to produce reactive oxygen species remain unknown. We re-investigated
      this problem by monitoring the luminol-enhanced chemiluminescence (CL) produced
      by LPS-stimulated equine neutrophils. The neutrophils were isolated from horse
      blood by discontinuous density gradient centrifugation (> or = 99% neutrophils;
      viability > or = 98%). Increasing concentrations of Escherichia coli (E. coli)
      LPS (from 0.01-10 microg ml(-1)) were used to activate the neutrophils. When LPS
      was used directly, without another stimulator, the respiratory burst of
      neutrophils was not activated (N=12 horses; n=5 assays per horse). On the
      contrary, when LPS was added to whole blood, the neutrophils isolated from this
      blood were stimulated in a LPS dose-dependent manner, but polymyxin B added to
      whole blood suppressed this stimulation (N=2; n=6). LPS dissolved in autologous
      equine plasma stimulated the isolated neutrophils in a dose-dependent manner from
      0.1-10 microg ml(-1) (N=5; n=12). Heat inactivation of the plasma abolished this
      CL increase (N=2; n=5). LPS added to equine albumin did not stimulate the
      isolated neutrophils (N=2; n=5). On the contrary, the addition of gamma-globulins
      (1 mg ml(-1)) to LPS (10 microg ml(-1)) led to the stimulation of neutrophils
      (N=2; n=5). We concluded that LPS did not directly stimulate the isolated equine
      neutrophils, but that plasmatic factors are needed for the stimulation of these
      cells by LPS.

PMID- 9764725
TI  - Modulation of lympho-proliferative responses of ovine peripheral blood
      mononuclear cells by Mycoplasma mycoides ssp. mycoides (LC type).
AB  - The present study was carried out to investigate the immunomodulating potential
      of M. mycoides ssp. mycoides (Mmm) (LC): a standard strain (Y-Goat, YG) and a
      local strain (M30) isolated from the pneumonic lung of a lamb during an outbreak
      of respiratory disease. The study was conducted in two parts to determine in
      vitro and in vivo aspects of the Mmm-induced modulation of cellular immune
      responses. In vitro experiments, using peripheral blood mononuclear cells (PBMC)
      of naive lambs, showed that live (Lv) or inactivated (Ina) antigens of Mmm
      (strains YG and M30) were not mitogenic for PBMC. Live antigens of both the
      strains, however, induced significant suppression of the PHA-driven lympho
      proliferative (LP) responses. Suppression of LP responses by infectious Mmm (both
      strains) was restored in the presence of exogenous recombinant human interleukin
      2 (rhIL-2). Following experimental inoculation of lambs with Mmm (YG), a
      significant reduction in non-specific LP responses was observed on days 6, 10 and
      14 post inoculation (p.i.). There was a slow but significant rise in memory LP
      responses to Mmm strains (YG and M30). Specific subset depletion studies, using
      immunomagnetic cell separation (IMCS) technique, carried out on days 10 and 14
      p.i., revealed that the OvCD4+ cell population was the main proliferating
      lymphocyte subset following an infection with Mmm (LC type).

PMID- 9764726
TI  - Immunohistochemical study of the local immune response to Fasciola hepatica in
      primarily and secondarily infected goats.
AB  - The distribution of CD2, CD4, CD8, gamma/delta T-lymphocytes, B-cells and IgG
      lambda-light chain (lambda-IgG) containing cells were analysed in the
      inflammatory infiltrate associated to hepatic lesions and gallbladder (HL), and
      in hepatic lymph nodes (HLN) of goats primarily and secondarily infected with
      Fasciola hepatica. In the HL, CD2 and CD8 T-cells were more numerous (p=0.01) in
      secondarily rather than in primarily infected goats, whereas CD4 T-lymphocytes
      were less numerous than CD8 and showed no significant change in both groups. The
      ratio CD4/CD8 was 0.66 and 0.39 for primarily and secondarily infected goats,
      respectively. In contrast, in the HLN, CD4 were more numerous than CD8 T-cells,
      the ratio CD4/CD8 was 2.0 in control, 1.5 and 1.3 in primary and secondary
      infections, respectively. Gamma/delta T-lymphocytes were scarce in the HL and
      moderate in the HLN of both primarily and secondarily infected animals. B-cells
      (IgM+, lambda-IgG+ or CD79+) varied from scarce or moderate in the HL to abundant
      in the HLN, where CD79+-cells were mainly located in lymphoid follicles and IgM
      and IgG in plasma-cells of the medullary cords, suggesting an intense local
      humoral immune response. However, this response did not prevent the hepatic
      damage in secondarily infected goats, in which hepatic lesions were more severe
      than in primarily infected ones.

PMID- 9764727
TI  - Characterisation of the primary local and systemic immune response in gnotobiotic
      lambs against rotavirus infection.
AB  - This study characterised the primary immune response in gnotobiotic lambs after
      infection with a lamb rotavirus (RV). Lambs were infected and killed over a 7
      week period together with controls. RV-ELISA and neutralising antibodies were
      determined in serum, nasal secretions, and intestinal scrapings. RV-antibody
      secreting cells (ASC) were enumerated in blood. Lymphocyte proliferations were
      determined in blood and gut-associated lymphoid tissues and cytokine expression
      was analysed in jejunal Peyer's patches (JPPs) and mesenteric lymph nodes (MLNs).
      Infected lambs cleared the virus by 8-9 days after infection without showing any
      clinical signs. The first indication of a specific immune response to RV was an
      increased expression of IL-4 mRNA in the JPPs in the infected group compared to
      the control group 3 days after infection. Rotavirus-specific IgA ASC in blood and
      IgA antibodies in serum and nasal secretions were detected from 7 days after
      infection followed at 10 days after infection by RV-specific IgG ASC and
      antibodies. Rotavirus-specific IgA antibodies were not detected in intestinal
      scrapings in the first 10 days after infection, but were detected by 52 days
      after infection. No RV-specific neutralising antibodies were seen in the
      intestine during the course of the experiment.

PMID- 9764728
TI  - Immunity to porcine rubulavirus infection in adult swine.
AB  - The immune response against the porcine rubulavirus was analyzed in
      experimentally infected adult pigs. High titers of virus neutralizing and
      hemagglutinating inhibitory antibodies were identified in infected animals. The
      antibody specificity was directed towards HN, M, and NP rubula virion proteins;
      immunodominance of HN proteins was demonstrated. Peripheral blood mononuclear
      cells from infected, but not from non-infected pigs proliferated in vitro in
      response to virus antigenic stimuli, showing a bell-shaped plot with the highest
      peak at 5 weeks post-infection. Virus-induced lymphoblasts expressed CD4+ CD8+
      phenotype, whereas lectin-induced lymphoblasts were mainly identified as CD4+ CD8
      cells. Phenotype analysis of freshly prepared PBMC revealed increased number of
      both monocytes (PoM1+) and total T lymphocytes (CD2+) early during infection,
      with reduced values of B lymphocytes at 4 weeks post-infection. Decrease in CD4+
      CD8- blood cells was observed at 3 weeks post-infection, whereas both CD4- CD8+
      and CD4+ CD8+ cells increased 1 and 4 weeks post-infection, respectively. This
      work discusses the relevance of CD4+ CD8+ T cells in the control of porcine
      rubulavirus infection.

PMID- 9764729
TI  - Characterisation of non-maternal serum proteins in amniotic fluid at weeks 16 to
      18 of gestation.
AB  - Proteins found in amniotic fluid are mainly serum proteins, probably of maternal
      origin. About 5% of the total protein concentration has the potential of being
      fetal or decidual in origin. Only a few of these proteins have been isolated and
      characterised. In order to describe the foetal and decidual components in
      amniotic fluid more extensively, a polyspecific antiserum to amniotic fluid at
      weeks 16-18 of gestation was raised. Specificities in the antiserum to serum
      proteins were removed by adsorption. Several proteins of non-serum protein origin
      reacted with the antiserum. Three of these proteins were chosen for isolation and
      further characterisation. With the use of immunological methods, SDS-PAGE and N
      terminal sequencing we identified two of the proteins as C-terminal propeptides
      of procollagen Type I and Type III, which have not hitherto been described in
      amniotic fluid. The third protein, called here protein-4, showed up as homologous
      to fetal antigen-1 (FA-1) and human dlk, containing EGF-like domains and
      associated with growth in neuroendocrine tissues and tumours.

PMID- 9764730
TI  - Valproate and carbamazepine comedication changes hepatic enzyme activities in
      sera of epileptic children.
AB  - Previous observation that valproic acid (VPA) and carbamazepine (CBZ) caused
      hepatic damage prompted us to investigate the effects of VPA or CBZ monotherapy
      and VPA + CBZ comedication on the number of hepatic enzyme activities in sera of
      epileptic children. This study compares alanine aminotransferase (ALT), aspartate
      aminotransferase (AST) and gamma-glutamyltransferase (GGT) activities in sera of
      children treated with VPA (n=42), or CBZ (n=36) taken as a monotherapy, with VPA
      + CBZ combined therapy (n=36). The effect of VPA alone is greater on the activity
      of AST than on other enzymes, while CBZ therapy changes primarily the activities
      of GGT. The mean catalytic activity of AST was significantly elevated in groups
      on VPA, CBZ and VPA + CBZ treatment (2.02-, 1.49- and 1.45-fold increase,
      respectively) as compared to the control values. Changes in the ALT activity
      followed different patterns. The maximal increase was observed in the CBZ group
      with a smaller increase in the group on VPA + CBZ polytherapy, whereas only 15%
      of patients receiving VPA showed an average 1.38-fold increase of the mean enzyme
      activity. Increase in the catalytic activity of GGT probably reflects the
      induction produced by the CBZ treatment, either alone or in combination. Children
      on CBZ monotherapy showed an increase of mean catalytic activity of about twofold
      in 56% of patients. Children on VPA + CBZ comedication showed a similar
      behaviour, while VPA alone produced a moderate (1.44-fold) increase in 23% of
      children. However, concentrations of VPA and CBZ in sera of patients receiving
      monotherapy were within the expected therapeutic limits, whereas subtherapeutic
      levels of VPA were found in 30% of children on VPA + CBZ comedication. We propose
      that individual dosage adjustment in VPA + CBZ polytherapy should be combined
      with monitoring of relevant enzyme activities in serum.

PMID- 9764731
TI  - Reported alcohol consumption and the serum carbohydrate-deficient transferrin
      test in third-year medical students.
AB  - The serum carbohydrate-deficient transferrin (CDT) test was performed on 143
      third-year medical students along with questionnaires for the self-reporting of
      alcohol consumption during the last 2 weeks, the last 6 months, and questions on
      any alcohol-related untoward events. We found that the CDT test has poor
      sensitivity for detecting binge drinking in our population of students, despite
      some likely under-reporting of drinking. Self-reporting of drinking is commonly
      unreliable, and we found no significant correlation between the CDT
      concentrations in serum and the magnitude of self-reported alcohol use during 2
      week and 6-month periods. Hangover was by far the commonest self-reported
      untoward event, and there was a highly significant relationship (P < 0.001)
      between drinking and untoward events. From a small population of non-drinkers, we
      estimated the reference ranges for CDT to be <27 U/l for men and <35 U/l for
      women.

PMID- 9764732
TI  - Modulation of LDL particle size after an oral glucose load is associated with
      insulin levels.
AB  - Individuals with a predominance of small low-density lipoprotein (LDL) particles
      appear to be at increased risk for coronary artery disease. The purpose of this
      study was to determine whether the LDL particle size was modulated in response to
      a 75-g oral glucose load. Overall, there were no significant changes in the LDL
      particle size after glucose load. However, the difference in LDL particle size
      (deltaLDL size) between the fasting and 2-h post-load states was inversely
      correlated with the fasting LDL particle size. Also, deltaLDL size was positively
      correlated with BMI and the post-load glucose levels. Forward stepwise regression
      analysis revealed three parameters as independent factors capable of modulating
      LDL particle size: BMI, fasting insulin, and post-load glucose levels. After
      adjustment for BMI and glucose levels, the levels of fasting and 2-h post-load
      insulin remain independent determinants of deltaLDL size. These results suggest
      that plasma insulin levels during glucose load modulate LDL particle size.

PMID- 9764733
TI  - Radio-enzymatic determination of histamine: interference by fluoride and possible
      activation of histamine methyl transferase.
AB  - The reproducibility of a radio-enzymatic method for determining plasma histamine
      was found to be affected by the anti-coagulant used for collecting blood.
      Recovery experiments from whole blood indicated that heparin yielded values that
      were more accurate than with EDTA or sodium fluoride; fluoride gave a mean value
      which was +41% higher than with heparin (P=0.054). Addition of fluoride to a
      standard calibration curve, and of increasing amounts to aliquots of 5 ng
      histamine also yielded higher values than in controls, up to +15% (P<0.1) and
      +14.1% (P=0.03) respectively. Fluoride did not affect the detecting system and
      was not contaminated with histamine; nor did it breakdown the methyl donor, S
      adenosyl-L-methionine. It is concluded that heparin is the anti-coagulant of
      choice and that fluoride may activate histamine methyl transferase from pig
      brain. Fluoride may possibly have a biological role as an enzyme-activator and a
      usefulness in the therapy of mastocytosis.

PMID- 9764734
TI  - Levels of lipid peroxidation product and glycated hemoglobin A1c in the
      erythrocytes of diabetic patients.
AB  - In diabetes, the glycation and subsequent browning (or glycoxidation) reactions
      are enhanced by elevated glucose concentrations. It is unclear whether or not the
      diabetic state per se also induces an increase in the generation of oxygen
      derived free radicals (OFRs). There is some evidence, however, that glycation
      itself may induce the formation of OFRs. OFRs could cause oxidative damage to
      endogenous molecules. We examined the relationship between the levels of lipid
      peroxidation and the levels of glycated hemoglobin A1c (GHbA1c) in erythrocytes
      of diabetic and healthy subjects. Lipid peroxidation was assessed in erythrocyte
      membrane lipids by monitoring peak height ratios of conjugated linoleic acid
      (CLA), one of the products of lipid peroxidation, to linoleic acid (LA) using gas
      chromatography-mass spectrometry (GC/MS). CLA is a collective term used to
      designate a mixture of positional and geometric isomers of LA in which the double
      bonds are conjugated. The peak height ratio of CLA to LA was used as a biomarker
      of lipid peroxidation. GHbA1c, an index of glycemic stress, was measured by high
      performance liquid chromatography. There were significantly increased ratios of
      CLA to LA in diabetic erythrocytes compared with control erythrocytes. These
      ratios of CLA to LA were also significantly correlated with GHbA1c values. This
      suggests that glycation via chronic hyperglycemia links lipid peroxidation in the
      erythrocytes of both diabetic and healthy subjects.

PMID- 9764735
TI  - Effect of cigarette smoking on plasma metalloproteinase-9 concentration.

PMID- 9764736
TI  - Chronological change of respiratory function in smokers with elevated serum
      carcinoembryonic antigen levels.

PMID- 9764738
TI  - Introduction of the Guest-Editors with a short review on history of optics in
      Jena.

PMID- 9764737
TI  - Trypsin digestion of histones inhibited by glucose.

PMID- 9764739
TI  - Scanning near-field optical microscopy in cell biology and microbiology.
AB  - Scanning a point light source in close proximity over a sample and recording the
      scattered or transmitted light intensity point by point allows one to record
      optical images with a resolution not limited by diffraction. An overview of this
      technique called scanning near-field optical microscopy (SNOM or NSOM) is given
      with emphasis on cell- and microbiology. After an introduction, where the basic
      features of the technique are explained, illustrative examples are presented,
      such as a HeLa cell, fluorescence labelled human chromosomes, super resolution
      fluorescence imaging, single molecule imaging and fluorescence resonance energy
      transfer between a single pair of dye molecules.

PMID- 9764740
TI  - Cell biological applications of scanning near-field optical microscopy (SNOM).
AB  - Scanning near-field optical microscopy (SNOM) yields high-resolution topographic
      and optical images and is an important technique for visualizing biological
      systems. We summarize the literature on SNOM of biological systems and present
      some of our recent applications in cellular biology. These include studies of: i)
      the binding of fluorescently conjugated lectins to cell surface glycoproteins on
      3T3 Balb/c cells, ii) molecular interactions by fluorescence resonance energy
      transfer using photobleaching techniques, and iii) green fluorescent protein
      (GFP) expressed in bacteria.

PMID- 9764741
TI  - Laser tweezers and optical microsurgery in cellular and molecular biology.
      Working principles and selected applications.
AB  - After focusing in a microscope, light can be used for micromanipulation of (sub
      )micrometer sized objects. Focused beams of classical light ablate elements of
      the cell division machinery and switch the beating of hearts on a cellular basis.
      Focused lasers (laser microbeams or optical scissors) allow in addition very
      precise nanomachining in a wide field of applications, from developmental biology
      to plant biotechnology. While in microbeam work high power densities and
      efficient light-tissue interactions are required, optical tweezers work in a
      complementary way: Moderate power densities and small absorption of the laser by
      the biological material is needed. With light pressure and optical gradient
      forces optical tweezers can be used to move microscopic objects, even in the
      interior of closed cells. In total, most mechanical micromanipulation techniques
      known from cellular and molecular biology can be replaced by their optical
      correlate and some applications are possible which cannot be performed
      micromechanically. When these optical microtools are operated at their maximum
      performance, the physical effects are as interesting as their biological
      applications: The laser microbeam can generate extreme local temperatures, which
      however are dissipated within a few tens of nanoseconds and therefore cause
      damage only very locally. The optical tweezers with a working wavelength in the
      optical window of biological material (600-1100 nm) exert piconewton forces
      without any mechanical contact. The present article discusses some quantitative
      physical aspects of microbeams and optical tweezers and gives a few selected
      examples of applications.

PMID- 9764742
TI  - Cell ablation studies in plant development.
AB  - As an alternative and complementary approach to genetic targeted ablation, laser
      ablation has been applied to a variety of plant systems to investigate the basics
      of development in plants. The recent relevant literature is reviewed and provides
      concrete examples of how root development in Arabidopsis and cell polarization in
      Fucus have been studied using laser microsurgery. Guidelines are proposed for
      researchers who would like to apply laser ablation techniques to a given
      developmental problem.

PMID- 9764743
TI  - Laser tweezers are sources of two-photon excitation.
AB  - The most important application of continuous wave (cw) near infrared (NIR)
      microbeams in cellular and molecular biology are single-beam gradient force
      optical traps, also called "laser tweezers". Laser tweezers have been used for
      optical picoNewton force determination as well as for 3D cellular and
      intracellular micromanipulation, such as optical spermatozoa transportation in
      laser-assisted in vitro fertilization. Light intensities in the MW/cm2 range are
      necessary to confine motile spermatozoa in the optical trap. The enormous photon
      concentration in space and time results in non-resonant two-photon excitation of
      endogenous and exogenous absorbers with electronic transitions in the ultraviolet
      and visible spectral range. Trap-induced two-photon excitation of intracellular
      flurorophores can be used to study metabolism and vitality of motile cells
      without additional fluorescence excitation sources. Therefore, laser tweezers as
      sources of two-photon excitation may act as novel non-linear tools in cell
      diagnostics. The far red/NIR trapping radiation, in particular <800 nm, may also
      excite endogenous absorbers such as NAD(P)H, flavins, porphyrins and cytochromes.
      Excitation of these cellular absorbers may result in oxidative stress via type I
      and type II photooxidation processes. Severe non-linear-induced cell damage in a
      variety of cells confined in <800 nm traps was found. Two-photon induced
      destructive effects are enhanced in multimode traps due to longitudinal mode
      beating phenomena. Pulsed laser sources are not suitable for safe optical
      trapping of living cells. The use of single frequency long-wavelength NIR traps
      (800 nm-1200 nm) for vital cell handling is recommended.

PMID- 9764744
TI  - Laser micromanipulation systems as universal tools in cellular and molecular
      biology and in medicine.
AB  - The UV-laser microbeam has been established as a valuable tool in a wide area of
      molecular biology as well as in medical research and applications. This system
      allows to cut or fuse microscopically small specimen. An important application of
      the cutting laser is laser microbeam microdissection (LMM) combined with laser
      pressure catapulting (LPC), which allows to procure single cells or small
      homogeneous cell areas for subsequent molecular analysis in an entirely "non
      contact" manner. With LMM minute tissue areas, single cells or chromosomes are
      microdissected and separated from their surroundings. Subsequently, LPC ejects
      the dissectates directly into the cap of a sample tube without any mechanical
      contact. This enables the rapid procurement of homogeneous specimen from less
      than one up to several hundreds of micrometers in diameter without encroachment
      of the adjacent region. The mRNA information of the selected specimen as well as
      of the remaining probe are well preserved, as demonstrated with laser isolated
      samples from a routinely prepared tissue section of a differentiated colorectal
      adenocarcinoma. Reverse transcription of specific mRNA coding for cytoplasmic
      beta-actin and subsequent hemi-nested PCR amplification was not impaired. Any
      kind of tissue, as well as single cells from different sources and even
      subcellular structures can be captured using this laser method. Wherever
      homogeneous samples are required to analyze cell or chromosome-specific genetic
      alterations such as in cancer research or prenatal diagnosis this unique and
      rapid laser micropreparation method will become a key technology of great value.

PMID- 9764745
TI  - Optical tweezers in pharmacology.
AB  - Current applications of optical tweezers in pharmacology are presented. The
      manufacture of cellular biosensor arrays employing optical tweezers is reviewed.
      Using this technique, a new approach to cellular drug screening, based on single
      cells patterned with the laser tweezers was introduced. Specific stimulation of
      different immobilized, viable cells could be shown simultaneously. Furthermore,
      the usefulness of optical tweezers for analyzing the interactions of ligands with
      cellular membrane receptors is demonstrated. The laser tweezers could
      successfully be used to compare neuron interactions with glycoproteins of the
      extracellular matrix by applying the optical tweezers as picotensometer. The
      forces of interactions between polystyrene beads coated with different proteins
      of the extracellular matrix and the cell membrane receptors of cerebellar neurons
      from postnatal day 6 (P6) mice were measured. When antibodies to the
      extracellular matrix proteins were added, forces were significantly reduced for
      the corresponding antigens but not for the other glycoproteins. This proved the
      specificity of the measured interactions. Information regarding the receptor
      anchorage of tenascin-C could be deduced.

PMID- 9764746
TI  - Time-gated autofluorescence microscopy of motile green microalga in an optical
      trap.
AB  - Ultrafast time-gated fluorescence imaging of optically trapped single motile
      cells is presented. The biflagellar green microalga Haematococcus pluvialis was
      confined with picoNewton trapping forces in the focal volume of a high numerical
      aperture objective by near infrared multitraps. Trapping radiation of 100 mW
      power at the sample was provided by a Nd:YLF laser (1047 nm) operating in the cw
      mode. Simultaneously, cellular autofluorescence was excited with a 633 nm
      picosecond 80 MHz laser diode. An ultrafast gated intensified slow scan CCD
      camera system with a tunable gate width (200 ps-1 ms) and tunable time-delay (0
      20 ns) between excitation and detection was used as fluorescence detector. We
      demonstrate fluorescence imaging of high temporal (sub-ns) and high spatial (sub
      microm) resolution and fluorescence lifetime determination of intracellular
      autofluorescence based on chlorophyll excitation. Exposure to the herbicide DCMU
      resulted in an increase of fluorescence intensity and lifetime by 250% and 150%,
      respectively.

PMID- 9764747
TI  - New time-resolved techniques in two-photon microscopy.
AB  - Microscopy is traditionally a tool for determining biological structures. Many
      recent advances in optical microscopy involves the incorporation of spectroscopy
      techniques to monitor biochemical states of microscopic structures in living
      cells and tissues. By minimizing tissue photodamage, two-photon excitation
      microscopy provides a new opportunity to study the dynamics of biological systems
      on time scales from nanoseconds to hours. This review will focus on a number of
      these new methods: two-photon time-lapse microscopy, two-photon photoactivation,
      two-photon correlated spectroscopy, two-photon single particle tracking and two
      photon lifetime microscopy.

PMID- 9764748
TI  - Time-gated fluorescence microscopy in cellular and molecular biology.
AB  - An experimental set-up for time-gated fluorescence spectroscopy and microscopy is
      described, and some recent applications in cellular and molecular biology are
      summarized. Selective detection of intrinsic fluorophores, in particular
      nicotinamide adenine dinucleotide (NADH) and flavins was demonstrated in living
      cells. Non-radiative energy transfer from reduced NADH to the mitochondrial
      marker rhodamine 123 was evaluated for probing mitochondrial malfunction in
      living cells. An increase of "energy transfer efficacy" up to a factor 4 was
      detected after inhibition of enzyme complexes of the respiratory chain. Two
      different fluorescence lifetimes of calcium orange were evaluated, whose relative
      intensities depended on calcium concentration. Therefore, fluorescence measured
      within two different time gates appeared to be suitable for ratio fluorometry of
      calcium. Time-gated fluorescence spectra of the membrane marker laurdan showed
      more pronounced changes than steady state spectra when temperature was increased
      from 24 degrees C to 38 degrees C. This may improve measurements of intracellular
      temperature. Time-gated detection of small amounts of porphyrins and their
      discrimination from a large fluorescent background caused by chlorophyll in
      transgenic tobacco plants again proved the advantages of time-gated fluorescence
      spectroscopy.

PMID- 9764749
TI  - Laser scanning microscopy in enzyme histochemistry. Visualization of cerium-based
      and dab-based primary reaction products of phosphatases, oxidases and peroxidases
      by reflectance and transmission laser scanning microscopy.
AB  - The reflectance mode of confocal laser scanning microscopy is suitable to detect
      cerium-based primary reaction products of oxidases (CeIV-perhydroxide) and
      phosphatases (CeIII-hydroxy-phosphate converted into CeIV-perhydroxy-phosphate)
      as well as of DAB-based primary reaction products (Ni-DAB, Ni-FeII-DAB and CeIV
      DAB complexes) of cytochrome C oxidase and peroxidases in vibratome, cryotome and
      semithin plastic sections. In combination with confocal detection 3D images with
      submicron spatial resolution can be obtained. Moreover, CeIV-perhydroxide, CeIV
      perhydroxy-phosphate, CeIV-DAB complexes and catechol-DAB polymers are highly
      absorptive. Among other additives, especially stable nitroxyl radicals led to a
      distinct improvement of the DAB staining in terms of sensitivity and proper
      localization. This was proven in addition by means of blotting a horseradish
      peroxidase dilution series during several experiments. In sections it was easily
      possible to record reflectance signals and high transmission contrast at the
      wavelength of the exciting argon ion laser (preferentially 488 nm). The results
      of an imbibition study of cerium-containing model precipitates indicate that the
      cerium generally should be oxidized prior to observation because the index of
      refraction of CeIV compounds is considerably higher than that of the
      corresponding CeIII compounds. A comparative numerical assessment of reflection
      intensities from reflectant parts in morphologically similar sections is
      possible. Confocal laser scanning microscopy offers a unique way for high
      resolution detection of primary histochemical reaction products being
      sufficiently reflective and/or absorptive. The proposed techniques may open new
      methodological possibilities for basic research and for medical diagnosis.

PMID- 9764750
TI  - Acousto-optic random-access laser scanning microscopy: fundamentals and
      applications to optical recording of neuronal activity.
AB  - A novel approach to laser scanning microscopy is presented that utilizes
      diffraction-based scanning principles to achieve fast random-access positioning
      of a focused laser beam. This non-imaging approach overcomes the speed limitation
      of present reflection-based scanning microscopes while maintaining high spatial
      resolution. The presented system combines conventional video microscopy with fast
      non-imaging scanning microscopy. Together with readily available optical
      indicators of neuronal activity, this system permits multi-site optical recording
      from living brain tissue. In this paper, we will review the underlying principles
      of laser scanning microscopy and the steps in development that led to the current
      acousto-optic scanning system. We will present typical signals recorded with the
      current system, and we will outline ongoing extensions of the system. We will
      also discuss the present limitation of this instrumentation and look into
      directions of future development.

PMID- 9764751
TI  - Fluorescence correlation microscopy (FCM)-fluorescence correlation spectroscopy
      (FCS) taken into the cell.
AB  - Confocal fluorescence correlation spectroscopy (FCS) and other confocal
      spectroscopic techniques are ideally suited for the analysis of molecular
      interactions at the subcellular level. However, one requires exact positioning in
      three dimensions within the cell. Our instrument integrates FCS with high
      sensitivity digital imaging microscopy and high precision positioning. We present
      first measurements of intracellular FCS, with specification of the instrumental
      requirements and methods of data analysis. We propose the term fluorescence
      correlation microscopy (FCM) for this extended modality of FCS.

PMID- 9764752
TI  - Fluorescence correlation spectroscopy as a tool to investigate chemical reactions
      in solutions and on cell surfaces.
AB  - Taking advantage of the present day possibilities for ultrasensitive detection by
      fluorescence, fluorescence correlation spectroscopy (FCS) has over the last ten
      years emerged as a potentially very powerful technique. In this article we
      present some results to illustrate the use of FCS for monitoring chemical
      kinetics on a molecular level and show how, for a wide range of chemical
      processes, the theoretical treatment can be strongly simplified. The experimental
      examples given include measurements of ion concentrations and buffer properties,
      electron transfer reactions, ligand-receptor interactions and diffusion of ligand
      receptor complexes in cell membranes. For each of these examples the properties
      of the FCS technique is discussed in relation to other established techniques
      used for that particular application. From these examples it is found that FCS
      can offer important complementary information and, due to the extreme sensitivity
      of the technique, new information not yet explored by other methods.

PMID- 9764753
TI  - Stress symposium in Johannesburg: plants versus humans.
AB  - On 18 February 1998, a 'Stress symposium' was held at the Rand Afrikaans
      University (RAU) in Johannesburg, South Africa. The meeting brought together
      people from both the plant and the human oxidative stress field, which was
      exemplified by a talk entitled 'Heat shock proteins in host-pathogen
      interactions: plants versus humans'. There were moments when it appeared as if
      the main difference between plants and humans was, as sung by Julos Beaucarne,
      that 'the human plant is the only one to be able to water itself...'

PMID- 9764754
TI  - Phosphorylation of RNA polymerase II C-terminal domain (CTD): a new control for
      heat shock gene expression?

PMID- 9764755
TI  - Stimulation of the stress-induced expression of stress proteins by curcumin in
      cultured cells and in rat tissues in vivo.
AB  - Curcumin, a major component of turmeric, a seasoning commonly used in Indian
      food, and a known antioxidant, anti-inflammatory and anti-carcinogenic agent, is
      a potent stimulator of the stress-induced expression of Hsp27, alphaB crystallin
      and Hsp70. When C6 rat glioma cells were exposed to arsenite (100 microM for 1
      h), CdCl2 (100 microM for 1 h) or heat (42 degrees C for 30 min) in the presence
      of 3-10 microM curcumin, induction of the synthesis of all three proteins was
      markedly stimulated, as detected by specific immunoassays, Western blot analysis
      and Northern blot analysis. A gel mobility shift assay revealed that curcumin
      prolonged the stress-induced activation of the heat shock element-binding (HSE
      binding) activity of heat shock transcription factor (Hsf) in the cultured cells.
      The stimulatory effect of curcumin on the responses to stress was also observed
      in BRL-3A rat liver cells and Swiss 3T3 mouse fibroblasts. Induction of Hsp27,
      alphaB crystallin and Hsp70 in the liver and adrenal glands of heat-stressed (42
      degrees C for 20 min) rats was also enhanced by prior injection of curcumin (20
      mg/kg body weight). As curcumin is a potent inhibitor of arachidonic acid
      metabolism, it is suggested that the mechanism of the stimulation by curcumin of
      the stress responses might be similar to that of salicylate, indomethacin and
      nordihydroguaiaretic acid.

PMID- 9764756
TI  - Presence of antibodies to heat stress proteins in workers exposed to benzene and
      in patients with benzene poisoning.
AB  - Heat shock or stress proteins (Hsps) are a group of proteins induced by a large
      number of xenobiotics, many of which are common in the working and living
      environment. The biological significance of the presence of antibodies against
      Hsps in humans is presently unknown. In the present study, 112 workers were
      selected and divided into four groups on the basis of their level of occupational
      exposure to benzene: a control group, two groups of workers exposed to either low
      (< 300 mg/m3) or high concentrations of benzene (> 300 mg/m3) and a group of
      workers who had experienced benzene poisoning. Blood samples from these workers
      were assayed for the number of peripheral white blood cells, concentration of
      hemoglobin, activities of serum superoxide dismutase (SOD), lymphocyte DNA damage
      and finally for the presence of antibodies to different human heat-shock proteins
      (Hsp27, Hsp60, Hsp71 and Hsp90). Benzene-poisoned workers showed a high incidence
      of antibodies against Hsp71 (approximately 40%) which was associated with a
      decrease in white blood cells (3.84+/-1.13 x 10(9)versus 7.68+/-1.84 x 10(9) in
      controls) and with an increase in activities of serum SOD (138.43+/-23.15
      micro/ml) and lymphocyte DNA damage (18.7%). These data suggest that antibodies
      against Hsps can potentially be useful biomonitors to assess if workers are
      experiencing or have experienced abnormal xenobiotic-induced stress within their
      living and working environment.

PMID- 9764757
TI  - Flow cytometry is a rapid and reliable method for evaluating heat shock protein
      70 expression in human monocytes.
AB  - The increasing interest in stress/heat shock proteins (Hsps) as markers of
      exposure to environmental stress or disease requires an easily applicable method
      for Hsp determination in peripheral blood cells. Of these cells, monocytes
      preferentially express Hsps upon stress. An appropriate fixation/permeabilization
      procedure was developed, combined with immunofluorescence staining and flow
      cytometry for the detection of the inducible, cytosolic, 72 kDa Hsp (Hsp70) in
      human monocytes. Higher relative fluorescence intensity was observed in cells
      exposed to heat shock (HS), reflecting a higher expression of Hsp70 in these
      cells as compared with cells kept at 37 degrees C. The heat-inducible increased
      Hsp70 expression was temperature- and time-dependent. Expression of Hsp70 was not
      uniform within the monocyte population, indicating the presence of subpopulations
      expressing variable levels of Hsp70 in response to HS. Simultaneous measurements
      of intracellular Hsp70 and membrane CD14 expression revealed that the higher
      Hsp70 inducibility coincided with the higher CD14 expression. Comparisons
      performed with biometabolic labelling, Western blotting, immunofluorescence and
      immunoperoxidase microscopic analysis, showed a high concordance between these
      different methods; however, cytometry was more sensitive for Hsp70 detection than
      Western blotting. Flow cytometric detection of intracellular Hsp70 is a rapid,
      easy and quantitative method, particularly suited for the determination of
      protein levels in individual cells from an heterogeneous population such as
      peripheral mononuclear blood cells, and applicable to cohort studies.

PMID- 9764758
TI  - Phosphorylation is not essential for protection of L929 cells by Hsp25 against
      H2O2-mediated disruption actin cytoskeleton, a protection which appears related
      to the redox change mediated by Hsp25.
AB  - Small stress proteins protect against the cytotoxicity mediated by oxidative
      stress. The relationship between Hsp25 expression and the integrity of the actin
      network was studied in H2O2-treated murine L929 fibrosarcoma cells overexpressing
      endogenous wild-type (wt-) or non-phosphorylatable mutant (mt-) Hsp25. We show
      here that both proteins prevented actin network disruption induced by a 1 h
      treatment with 400 microM H2O2. In contrast, SB203580, a p38 MAPkinase inhibitor
      which suppresses Hsp25 phosphorylation, abolished the protective activity
      conferred by both wt- and mt-Hsp25. Hence, phosphorylation does not appear
      essential for Hsp25 protective activity against H2O2-induced actin disruption,
      and SB203580-sensitive events other than Hsp25 phosphorylation may be important
      for actin network regulation. Since, in L929 cells, wt- or mt-Hsp25 expression
      modulates intracellular glutathione levels, analyses were performed which
      revealed a direct correlation between glutathione and the integrity of the actin
      network. Moreover, laser scanning confocal immunofluorescences revealed that only
      a small fraction of wt- or mt-Hsp25 colocalized with actin microfilaments. Taken
      together, our results suggest that, in L929 cells, the protection against actin
      network disruption is probably a consequence of the redox change mediated by
      Hsp25 rather than a direct effect of this stress protein towards actin.

PMID- 9764760
TI  - Purification and characterization of chaperonins 60 and 10 from Methylobacillus
      glycogenes.
AB  - Two proteins belonging to the group I chaperonin family were isolated from an
      obligate methanotroph, Methylobacillus glycogenes. The two proteins, one a GroEL
      homologue (cpn60: M. glycogenes 60 kDa chaperonin) and the other a GroES
      homologue (cpn10: M. glycogenes 10 kDa chaperonin), composed a heteropolymeric
      complex in the presence of ATP. Both proteins were purified from crude extracts
      of M. glycogenes by anion-exchange (DEAE-Toyopearl) and gel-filtration (Sephacryl
      S-400) chromatography. The native molecular weights of each chaperonin protein as
      determined by high-performance liquid chromatography (HPLC) gel-filtration were
      820 000 for cpn60 and 65 000 for cpn10. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis revealed that the subunit molecular weights of cpn60 and cpn10
      were 58 000 and 10 000, respectively. Both cpn60 and cpn10 possessed amino acid
      sequences which were highly homologous to other group I chaperonins. M.
      glycogenes cpn60 displayed an ATPase activity which was inhibited in the presence
      of cpn10. The chaperonins also displayed an ability to interact with and
      facilitate the refolding of Thermus malate dehydrogenase and yeast enolase in a
      manner similar to that of GroEL/ES. The similarities between the Escherichia coli
      GroE proteins are discussed.

PMID- 9764759
TI  - Constitutive expression of heat shock proteins Hsp90, Hsc70, Hsp70 and Hsp60 in
      neural and non-neural tissues of the rat during postnatal development.
AB  - Heat shock proteins (Hsps) are a group of highly conserved proteins, that are
      constitutively expressed in most cells under normal physiological conditions.
      Previous work from our laboratory has shown that neurons in the adult brain
      exhibit high levels of Hsp90 and Hsc70 mRNA and protein, as well as basal levels
      of Hsp70 mRNA. We have now investigated the expression of Hsp90, Hsc70, Hsp60 and
      Hsp70 in neural and non-neural tissues of the rat during postnatal development, a
      time of extensive cell differentiation. Western blot analysis revealed
      constitutive expression of these Hsps early in postnatal development.
      Developmental profiles of these Hsps suggest that they are differentially
      regulated during postnatal development of the rat. For example, while levels of
      Hsp90 decrease somewhat in certain developing brain regions, levels of Hsp60 show
      a developmental increase, and Hsc70 protein is abundant throughout postnatal
      neural development. Low basal levels of Hsp70 are also observed in the developing
      and adult brain. A pronounced decrease in Hsp90 and Hsc70 was observed during
      postnatal development of the kidney while levels of Hsp60 increased. In addition,
      tissue-specific differences in the relative levels of these Hsps between brain
      and non-brain regions were found. Immunocytochemical studies demonstrated a
      neuronal localization of Hsp90, Hsc70 and Hsp60 at all stages of postnatal
      development examined as well as in the adult, suggesting a role for Hsps in both
      the developing and fully differentiated neuron. The developmental expression of
      subunit IV of cytochrome oxidase was similar to that of Hsp60, a protein
      localized predominantly to mitochondria.

PMID- 9764761
TI  - Complementary and alternative medicine: essential for the future of effective,
      affordable healthcare?

PMID- 9764762
TI  - Big changes at National Cancer Institute.

PMID- 9764763
TI  - New chair of alternative medicine at the State Medical University of Crimea in
      Simferopol, Ukraine.

PMID- 9764764
TI  - A lost opportunity to discover antibiotics.

PMID- 9764765
TI  - Effects of lavender straw on stress and travel sickness in pigs.
AB  - OBJECTIVE: To observe pigs during road journeys in order to establish whether
      lavender straw was likely to decrease stress and incidence of travel sickness.
      SUBJECTS: Forty 70-kg Large White pigs were transported by road for 2 hours, 20
      animals each day, over a 2-day period. DESIGN: On day 1, ample wheat straw was
      provided as bedding such that the floor of the vehicle was entirely covered
      (straw condition). On day 2, lavender straw was provided as bedding (lavender
      condition). During the journey, direct behavioral observations of the
      individually marked pigs were made by scanning every 10 minutes for incidence of
      standing and lying along with the less severe symptoms of travel sickness
      (foaming at the mouth and repetitive chomping). Incidences of retching and
      vomiting were noted as they occurred. A general activity index was also scored
      every 10 minutes (5 = high activity, 1 = low activity). Saliva samples were taken
      from each animal at different stages of the journey for analysis of cortisol.
      RESULTS: Pigs stood more when in the straw condition, but were more active when
      standing in the lavender condition. Symptoms of travel sickness appeared to be
      less acute in the lavender condition, with more animals exhibiting the less
      severe symptom, foaming and chomping (a total of 3 in straw compared with 6 in
      lavender), but fewer animals showing the more severe symptoms of retching and
      vomiting (in straw, 3 retched, 6 vomited; in lavender 0 retched, 3 vomited). A
      total of 6 animals retched or vomited in the straw condition but only 3 in the
      lavender. There was a significant difference in mean concentrations of cortisol
      between conditions but this was due to a difference in mean baseline
      concentrations between groups. CONCLUSION: Addition of lavender straw appeared to
      decrease incidence and severity of travel sickness but not overall levels of
      stress (as measured by concentrations of salivary cortisol).

PMID- 9764766
TI  - Characteristics of users and nonusers of alternative medicine in dermatologic
      patients attending a university hospital clinic: a short report.
AB  - OBJECTIVES: To study the characteristics of users of alternative medicine in
      dermatologic outpatients attending a university clinic. DESIGN: A cross-sectional
      study analyzed by using a case-control methodology. SETTING, SUBJECTS, AND STUDY
      MEASURES: 118 dermatologic patients attending an outpatient university clinic
      responded to a structured questionnaire concerning demographic data, medical
      history, experience with alternative medicine, health beliefs, lifestyle, and
      locus of control. RESULTS: Thirty-five percent of the patients reported having
      used some form of alternative medicine. Use was related to disease duration, but
      not to patients' beliefs regarding whether or not they could influence their own
      health, nor to dissatisfaction with orthodox medicine. The most common reason for
      trying alternative medicine was that they "wanted to try everything" in an
      attempt to cure the skin disease. Users stated to a greater extent than nonusers,
      that they exercised sufficiently, possibly indicating that they are more health
      conscious. CONCLUSIONS: The study suggests that dermatologic patients using
      alternative medicine in general do not differ with regard to personal
      characteristics from nonusers. Rather, it appears that patients with long
      standing skin disease turn to alternative medicine as a complement to orthodox
      treatment.

PMID- 9764767
TI  - Treatment of human immunodeficiency virus-positive patients with complementary
      and alternative medicine: a survey of practitioners.
AB  - OBJECTIVE: To investigate complementary and alternative medicine (CAM) practices
      provided to human immunodeficiency virus (HIV)-infected individuals, provider
      experience in HIV disease, patients' characteristics, provider perceptions of
      treatment effectiveness, and feasibility and interest in future studies. DESIGN:
      Mailed survey. PARTICIPANTS: 117 providers, recruited from professional
      associations and conferences, who offer CAM therapies to HIV-infected
      individuals. OUTCOME MEASURES: Provider credentials, patient descriptors,
      treatments prescribed and their perceived effectiveness, health service
      information, medical information charted, and research participation capability
      and interest. RESULTS: Providers are treating patients at all stages of HIV
      disease with a variety of CAM practices, claiming a mean of 6.5 years of HIV
      disease treatment experience and 105 HIV-positive patients in treatment per
      provider (solo practice or clinic). Eighty percent of respondents report holding
      state licenses to practice. A total of 115 different CAM therapies with an
      average of 12 treatments per provider were used. Ninety percent of providers
      claimed their therapies were "somewhat" to "very effective" on all disease
      stages, indicating effectiveness for symptom management (96%), quality of life
      (98%), raising or maintaining CD4+ lymphocyte levels (66%), slowing progression
      to acquired immunodeficiency syndrome (AIDS) (69%), and extending survival (73%).
      Research readiness and willingness was reported by a majority of respondents.
      CONCLUSIONS: Providers with substantial experience treating HIV disease with a
      range of CAM practices claim effectiveness for their methods. Providers are
      generally willing to participate in studies that would examine such claims and
      appear to have the capacity meaningfully to contribute. These claims should be
      investigated.

PMID- 9764768
TI  - The scientific rediscovery of an ancient Chinese herbal medicine: Cordyceps
      sinensis: part I.
AB  - This review presents Cordyceps sinensis (Berk.) Sacc., a fungus highly valued in
      China as a tonic food and herbal medicine. The extant records show the continued
      use of C. sinensis is now centuries old. The major chemical, pharmacological, and
      toxicological studies on C. sinensis and the various derived, cultured, fermented
      mycelial products currently in use are reviewed from the English and Chinese
      literature. Preclinical in vitro and in vivo studies and clinical blinded or open
      label trials in to date over 2000 patients are reviewed. These studies show the
      main activities of the fungus in oxygen-free radical scavenging, antisenescence,
      endocrine, hypolipidemic, antiatherosclerotic, and sexual function-restorative
      activities. The safety of the fungus, its effects on the nervous system, glucose
      metabolism, the respiratory, hepatic, cardiovascular, and immune systems,
      immunologic disease, inflammatory conditions, cancer, and diseases of the kidney
      will be reviewed in the second part of this article to be published in the winter
      issue of this journal.

PMID- 9764769
TI  - Aspects of ethnobotanical medicine in southeast Nigeria.
AB  - OBJECTIVE: To document the diversity and traditional use of tropical plants as
      medicine by the indigenous people of southeast Nigeria. DESIGN: Information was
      obtained by interviews conducted with the aid of questionnaires and facilitators
      during field surveys carried out from January 1993 to June 1994. Voucher
      herbarium specimens were identified at the University of Nigeria, Nsukka
      Herbarium, in collaboration with Bernhard Zepernick (former Curator), Botanisches
      Museum, Berlin. Specimens were photographed. RESULTS: Data are summarized in the
      form of a table, summarizing the plants commonly used by the traditional doctors
      or medicine men. Herbal preparations are arranged alphabetically under family and
      species. The data are presented in the order: botanical name, collection number,
      vernacular name, locality, plant habit/status, and reported medicinal
      applications.

PMID- 9764770
TI  - Traditional alternatives as complementary sciences: the case of Indo-Tibetan
      medicine.
AB  - Traditional medical systems, like those preserved in Asia, pose a challenge
      because they involve theories and practices that strike many conventionally
      trained physicians and researchers as incomprehensible, even nonsensical. Should
      modern medicine continue to dismiss these systems as unscientific, therefore
      worthy of debunking rather than serious study; view them as sources of
      alternatives, possibly effective but hidden in a matrix of prescientific custom
      and belief; or do they represent something like a complementary science of
      medicine? We make the latter argument using the example of Indo-Tibetan medicine.
      Indo-Tibetan medicine is based on analytic models and methods that are rationally
      defined, internally coherent, and make testable predictions, therefore meeting
      current definitions of "science." The possibility of multiple, complementary
      sciences is a consequence of certain findings in physics that have led to a view
      of science as a set of tools-instruments of social activity that depend on
      learned agreement in aims and methods-rather than as a monolith of absolute
      objective truth. Implications of this pluralistic view of science for medical
      research and practice are discussed.

PMID- 9764772
TI  - M.D. programs in the United States with complementary and alternative medicine
      education: an ongoing listing.

PMID- 9764771
TI  - Reflections on the nature of the consultation.

PMID- 9764773
TI  - Adaptation to promiscuous usage of CC and CXC-chemokine coreceptors in vivo
      correlates with HIV-1 disease progression.
AB  - OBJECTIVE: To study coreceptor usage of sequential primary HIV-1 isolates in a
      longitudinal follow-up cohort of HIV-1-infected men to understand its
      contribution to pathogenesis of HIV disease. DESIGN: Viral coreceptor usage of
      sequential primary isolates from HIV-1-infected individuals was examined at
      various timepoints and data was compared with CD4 cell counts, rates of disease
      progression and beta-chemokine production. METHODS: Fifty-eight sequential
      primary isolates were obtained from four rapid progressors, six late progressors,
      and three long-term nonprogressors (LTNP) and their coreceptor usage was examined
      by infection of peripheral blood mononuclear cells (PBMC) from donors with wild
      type or non-functional CC-chemokine receptor (CCR)-5, and by infection of GHOST4
      cells expressing CD4 and various chemokine receptors [CCR-1-CCR-5, CXC-chemokine
      receptor (CXCR)-4, BOB/GPR15, BONZO/STRL33]. Production of RANTES and macrophage
      inflammatory protein (MIP)-1beta was examined using unstimulated or
      phytohemagglutinin (PHA)-stimulated PBMC isolated from these individuals at
      multiple timepoints during infection. RESULTS: A switch from single CCR-5
      coreceptor usage to multiple coreceptor usage occurred in all four rapid
      progressors and three out of six late progressors. In addition to the commonly
      used coreceptors CXCR-4, CCR-5, and CCR-3, some of the viruses isolated from
      patients in the terminal stage of infection also used CCR-1, CCR-2b, CCR-4, and
      BOB as coreceptors. The emergence of viral variants capable of utilizing multiple
      coreceptors generally preceded CD4 cell decline to < 200 x 10(6)/l and correlated
      with the onset of AIDS. In contrast, three LTNP maintained exclusive usage of CCR
      5 over a period of 7-12 years post-infection. Endogenous production of RANTES and
      MIP-1beta by PBMC from LTNP was not significantly different from rapid and late
      progressors. However, PHA-driven production of both chemokines was significantly
      higher in LTNP, suggesting that in vivo activating stimuli might curtail HIV
      replication by inducing these chemokines. CONCLUSIONS: Viral variants capable of
      utilizing a broad range of coreceptors correlated with HIV-1 disease progression.
      In contrast, LTNP maintain exclusive usage of CCR-5 and produce higher levels of
      beta-chemokines. Thus, both viral and host determinants leading to the emergence
      of viral variants capable of using an expanded range of coreceptors may be likely
      determinants of disease progression.

PMID- 9764774
TI  - Target cell availability and the successful suppression of HIV by hydroxyurea and
      didanosine.

PMID- 9764775
TI  - Cost-effectiveness and cost-benefit in the prevention of mother-to-child
      transmission of HIV in developing countries. Ghent International Working Group on
      Mother-to-Child Transmission of HIV.

PMID- 9764776
TI  - Prognostic significance of plasma markers of immune activation, HIV viral load
      and CD4 T-cell measurements.
AB  - OBJECTIVE: To evaluate the prognostic significance for AIDS occurrence of plasma
      levels of immune activation markers in comparison with and in conjunction with
      HIV viral load and CD4 T-cell measurements. DESIGN: A retrospective analysis was
      conducted of three plasma activation markers, the soluble tumor necrosis factor
      (TNF) receptor II (TNF-RII), neopterin and soluble interleukin-2 receptor levels,
      and of CD4 T-cell levels and plasma HIV viral load. SUBJECTS: The participants
      were 659 men taking part in the University of California Los Angeles Multicenter
      AIDS Cohort Study who were HIV-seropositive but AIDS-free in 1985. MAIN OUTCOME
      MEASURE: Clinically defined AIDS within 3 years. Failure time statistical
      regression models for the time to development of AIDS were used to assess
      prognostic capacity of the parameters alone and in combination. RESULTS: All the
      markers had prognostic capability. The levels of the three plasma activation
      markers correlated well with each other (median r = 0.61). They related less well
      with HIV RNA plasma levels (median r = 0.50) and least well with CD4 cell levels
      (median r = 0.36). Furthermore, plasma marker levels were shown to be able to
      stratify patients for prognosis within all the major categories of CD4 T-cell and
      HIV RNA levels. CONCLUSIONS: Plasma levels of soluble TNF-RII and other soluble
      markers of immune activation have prognostic capabilities which are different
      from HIV and CD4 T-cell levels. Combination of a single plasma activation marker
      measurement (such as soluble TNF-RII) with CD4 T-cell levels improved the
      prognostic capability of each. A new graphic technique for presenting prognostic
      capability indicated that plasma soluble TNF-RII and CD4 cell levels are better
      prognostic factors than HIV plasma level with CD4 cells < 200 x 10(6)/l.
      Inexpensive tests for one of the plasma activation markers, such as soluble TNF
      RII or neopterin, can be useful for evaluations of HIV disease course, especially
      when expensive equipment, technical expertise and funding required for flow
      cytometry and for HIV load measurements are not readily available.

PMID- 9764777
TI  - Neutralizing antibodies are positively associated with CD4+ T-cell counts and T
      cell function in long-term AIDS-free infection.
AB  - OBJECTIVES: To assess the dynamics of neutralizing antibodies (NAb) in long-term
      AIDS-free HIV-1-infected subjects and establish correlations with known markers
      of disease progression. DESIGN: Cross-sectional study using sera collected from
      long-term non-progressors (LTNP) 8 years after seroconversion or study entry.
      Longitudinal study using sera collected from LTNP at 0, 0.5, 1, 2, 4, 6, 8 and 10
      years after seroconversion and, as controls, from rapid progressors. METHODS:
      Individuals with documented AIDS-free HIV-1 infection for at least 8 years were
      evaluated for NAb against five heterologous HIV-1 primary isolates. In the cross
      sectional study, serum viral RNA levels, CD4+ T-cell numbers and T-cell function
      were determined on samples collected during the eighth year of follow-up. For the
      longitudinal study, NAb were assessed in sequential sera taken from LTNP and
      rapid progressors. RESULTS: Serum neutralization titres found in individual sera
      differed from one HIV-1 isolate to another, were detected in 49-76% of LTNP,
      without correlation with the coreceptor usage of the isolate, and were positively
      associated with CD4+ T-lymphocyte counts (P = 0.0041) and T-cell function (P =
      0.04). No correlation was found between NAb and the level of viral RNA in serum
      or the rate of CD4+ T-cell decline. Longitudinal analysis of sera from LTNP and
      rapid progressors showed that although several subjects in both groups had
      neutralizing activity at seroconversion, it thereafter became lower or no longer
      detectable. NAb were again found 1-4 years later and stably persisted in LTNP,
      but remained undetectable or at low levels in rapid progressors. CONCLUSIONS: NAb
      were preferentially found in subjects with relatively preserved T-cell function
      and CD4+ T-cell numbers. In these individuals, neutralizing activity against
      heterologous isolates increased with time. These data suggest that the capacity
      to produce broadly NAb is a function of the integrity of the immune system.

PMID- 9764778
TI  - Change in fluconazole susceptibility patterns and genetic relationship among oral
      Candida albicans isolates.
AB  - OBJECTIVE: To assess the genetic homogeneity or heterogeneity within each set of
      Candida albicans isolates colonizing/infecting the oral cavities of HIV-infected
      patients undergoing azole therapy when changes in susceptibility to fluconazole
      were detected. DESIGN: Fourteen HIV-positive patients suffering recurrent
      episodes of oral candidosis were prospectively followed from the first episode to
      the isolation of strains with decreased susceptibility to fluconazole. The
      strains of C. albicans isolated either from episodes or controls throughout the
      prospective study were analysed. METHODS: Electrophoretic karyotyping and
      hybridization with the repeated sequence probe 27A were used to delineate
      sequential isolates. In vitro susceptibility tests to fluconazole and
      ketoconazole were also performed. The results obtained by DNA fingerprinting with
      the probe combined with computer-assisted analysis were used to assess the
      genetic relationships amongst the strains. In addition, comparison with the
      genetic relatedness of a group of geographically unrelated strains was made.
      RESULTS: Isogenic populations of sequential isolates were observed only in two
      patients; 12 patients harboured heterogenic populations over time, although in 11
      patients there was a predominant strain that was isolated more than once, and
      only one of these patients carried strains with a similarity index less than 80%.
      With the exception of two patients, each patient carried a major strain that
      became less susceptible to fluconazole. The similarity index for the unrelated
      strains was 59%. CONCLUSIONS: HIV-infected patients may carry a mixed population
      of strains, but the strains tend to be related to each other. The strains were
      maintained throughout the course of infection and at least one developed
      secondary resistance to fluconazole.

PMID- 9764779
TI  - HIV protease genotype and viral sensitivity to HIV protease inhibitors following
      saquinavir therapy.
AB  - OBJECTIVE: To examine the relationship between HIV protease genotype and altered
      protease inhibitor sensitivity of isolates from patients after therapy with
      saquinavir (SQV) in its hard gelatin formulation. DESIGN: Forty-one post-therapy
      isolates and corresponding baseline samples were obtained from 37 patients in
      four different clinical trials after therapy with SQV for 16-147 weeks. Post
      therapy isolates were selected on the basis of preliminary sequence or drug
      sensitivity data. RESULTS: Fifteen out of 17 isolates without detectable Val-48
      or Met-90 mutations retained sensitivity to SQV. (The remaining isolates showed
      only a marginal increase in median inhibitory concentration.) In addition, three
      out of 15 isolates with Met-90 retained sensitivity to all other protease
      inhibitors tested (indinavir, ritonavir, amprenavir, nelfinavir). Of the isolates
      showing reduced sensitivity to SQV, six out of 22 retained sensitivity to all
      other protease inhibitors, whereas only four out of 22 showed broad cross
      resistance to all protease inhibitors tested. The reduction in sensitivity
      correlated closely with the presence of Val-48 or Met-90. Subsequent accessory
      substitutions were also linked to reduced sensitivity. However, significant
      linkage was observed only between mutations at residues 48 and 82 and between
      those at residues 82 and 74. CONCLUSIONS: Recruitment of Val-48/Met-90 mutations
      was not found to be synonymous with cross-resistance. Indeed, the majority of
      isolates with these mutations retained sensitivity to at least one protease
      inhibitor (Val-48, 86%; Met-90, 77%). The recruitment of accessory mutations may
      occur only after the selection of key resistance mutations. Furthermore, Met-90
      was found to be a poor marker of cross-resistance in SQV-treated patients.

PMID- 9764780
TI  - Suppression of plasma viral load below 20 copies/ml is required to achieve a long
      term response to therapy.
AB  - BACKGROUND: Current guidelines state that the goal of antiretroviral therapy for
      HIV-infected individuals is to suppress plasma viral load (pVL) to below 400
      copies/ml. METHODS: Predictors of achieving and maintaining pVL suppression were
      examined in a randomized trial of combinations of zidovudine, nevirapine and
      didanosine in patients with CD4+ T cell counts of between 200 and 600 x 10(6)
      cells/l who were naive to antiretroviral therapy and AIDS-free at enrolment.
      RESULTS: One hundred and four patients had pVL > 500 copies/ml at baseline and a
      pVL nadir below 500 copies/ml. Of these, 77 patients experienced an increase in
      pVL above 500 copies/ml. The median number of days of pVL suppression to below
      500 copies/ml was 285 (42) for patients with pVL nadir < or = (>) 20 copies/ml (P
      = 00.0001). The relative risk of an increase in pVL above 500 copies/ml
      associated with a pVL nadir below 20 copies/ml was 0.11 (P = 0.0001). The
      relative risks of an increase in pVL above 5000 copies/ml associated with a pVL
      nadir below 20 copies/ml or between 20 and 400 copies/ml were 0.05 [95%
      confidence interval (CI), 0.02-0.12] and 0.37 (95% CI, 0.23-0.61) respectively,
      compared with individuals with a pVL nadir > 400 copies/ml. Individuals with a
      pVL nadir < or = 20 copies/ml were at a significantly lower risk of virologic
      failure than individuals with a pVL nadir of between 21 and 400 copies/ml (P =
      0.0001). CONCLUSIONS: Our results demonstrate that suppression of pVL below 20
      copies/ml is necessary to achieve a long-term antiretroviral response. Our data
      support the need for a revision of current therapeutic guidelines for the
      management of HIV infection.

PMID- 9764781
TI  - Treatment response and durability of a double protease inhibitor therapy with
      saquinavir and ritonavir in an observational cohort of HIV-1-infected
      individuals.
AB  - OBJECTIVE: To evaluate treatment response, durability and tolerance of a four
      drug regimen including saquinavir and ritonavir in combination with either
      zidovudine/lamivudine or stavudine/lamivudine. DESIGN: Observational cohort of
      HIV-positive individuals. METHODS: Viral load, CD4+ and CD8+ T lymphocyte counts
      were assessed at intervals of 1-3 months in subjects commencing therapy between
      July 1996 and November 1996. Adverse events were evaluated as well as risk
      factors for therapeutic failures. RESULTS: A group of 56 male patients were
      included and followed for 48 weeks. Of these, 66% had already taken a protease
      inhibitor. Viral load dropped by a median 1.98 log10 HIV RNA copies/ml from
      baseline (interquartile range: 1.49-2.46) and became undetectable (< 400
      copies/ml) in 68% of patients. Response varied: 9% were non-responders (HIV RNA
      reduction < 0.5 log10 copies/ml) and 23% were incomplete responders (nadir of HIV
      RNA > 400 copies/ml). After 48 weeks, viral load remained undetectable in 49%.
      Median CD4+ T lymphocyte count increased from 191 x 10(6) to 418 x 10(6) cells/l
      (range, 241-537 x 10(6) cells/l). Although protease inhibitor and nucleoside
      pretreatment selected for drug-resistant viral mutants, only the protease
      inhibitor experience was identified as a risk factor for therapeutic failure.
      Adverse events occurred in 73% of patients and led to a change of therapy in 9%.
      CONCLUSION: Despite advanced HIV disease and pretreatment with multiple
      antiretroviral drugs, a strong initial treatment response to this drug regimen
      was observed. However, virological failure occurred in 51% of patients after 48
      weeks and frequent adverse events complicated therapy.

PMID- 9764782
TI  - Clinical outcome and predictive factors of failure of highly active
      antiretroviral therapy in antiretroviral-experienced patients in advanced stages
      of HIV-1 infection.
AB  - OBJECTIVE: To verify the effectiveness of highly active antiretroviral therapy
      (HAART) and to identify any factors predictive of clinical outcome in a clinical
      setting. DESIGN: Observational study. METHODS: Treatment failure (i.e., the
      occurrence of new or recurrent AIDS-defining events, death or any definitive
      discontinuation) and the course of CD4+ cell counts and HIV RNA copies were
      evaluated in 250 heavily pretreated HIV-infected patients starting HAART [153
      with indinavir (IDV), 55 with ritonavir (RTV), 43 with saquinavir (SQV)].
      Univariate and multivariate analyses were performed to identify predictors of
      worse outcome. RESULTS: During a median follow-up of 8 months, 75 patients (30%)
      had treatment failure because of the occurrence of an AIDS-defining event or
      death (n = 24), inefficacy (n = 24), or severe intolerance (n = 27). Twenty new
      and six recurrent AIDS-defining events, and nine deaths occurred (six out of 20
      AIDS-defining events and two out of nine deaths within 1 month of treatment).
      CD4+ counts were above 200 x 10(6)/l at AIDS diagnosis in only two patients. None
      of the SQV patients, 12 (7.8%) of the IDV patients, and 15 (27.3%) of the RTV
      treated patients were considered non-compliant. The SQV-containing regimens
      independently correlated with treatment failure (relative risk, 2.46; 95%
      confidence interval, 1.20-5.03; versus IDV). Low compliance partially determined
      outcome in RTV-treated patients; both severe immunodepression and AIDS at
      baseline were predictive of treatment failure. There was a 10-fold increase in
      CD4+ cell counts in the patients treated with IDV and RTV; the best virological
      outcome occurred in IDV-treated patients, with 68.4% of patients showing
      undetectable HIV RNA copies after 6 months. CONCLUSIONS: HAART was effective in
      70% of patients; low compliance and previous AIDS diagnosis represented
      predictive factors of therapy failure.

PMID- 9764783
TI  - The relative prognostic value of plasma HIV RNA levels and CD4 lymphocyte counts
      in advanced HIV infection.
AB  - OBJECTIVE: It has been suggested that the plasma HIV RNA level is a better
      predictor of AIDS and death than the CD4 lymphocyte count. We assessed whether
      the prognostic value of plasma virus levels was different according to the CD4
      count. DESIGN: Prospective cohort study of HIV-infected patients followed for a
      median of 2.91 years (range, 0.02-4.54). SETTING: Department of Infectious
      Diseases at Rigshospitalet, Copenhagen, Denmark. PARTICIPANTS: A group of 255 HIV
      infected individuals with an initial measurement of CD4 lymphocyte count and
      plasma HIV RNA. MAIN OUTCOME MEASURE: Survival time. RESULTS: The plasma HIV RNA
      (median 101410 copies/ml; range (range 200-7200000) and the CD4 lymphocyte count
      (median 250 cells x 10(6)/l; range 1-1247) were negatively correlated (Pearson r
      = -0.53; P < 0.00001). Of the 255 patients, 110 died during follow-up. Overall, a
      higher HIV RNA level was associated with increased risk of death, but the
      association was smaller in patients with lower CD4 lymphocyte counts (test for
      interaction P < 0.0001). In patients with CD4 count below 50 cells x 10(6)/l the
      association between HIV RNA and risk of death was not statistically significant
      (relative hazard per 10-fold higher HIV RNA level was 1.53; P = 0.11; adjusted
      for age and CD4 count) while that between the CD4 count and risk of death was
      highly significant (relative hazard per 50% lower CD4 count 1.38; P = 0.005;
      adjusted for age and HIV RNA level). CONCLUSIONS: Patients were relatively
      lightly treated with antiretroviral drugs both before and during this study. In
      this situation, it appears that the HIV RNA level has a relatively weak
      association with risk of death in patients with advanced HIV infection and that
      the CD4 lymphocyte count is probably more useful in assessing prognosis.

PMID- 9764785
TI  - Effects of vitamin E and C supplementation on oxidative stress and viral load in
      HIV-infected subjects.
AB  - OBJECTIVES: The HIV-infected population is known to be oxidatively stressed and
      deficient in antioxidant micronutrients. Since in vitro replication of HIV is
      increased with oxidative stress, this study assessed the effect of antioxidant
      vitamin supplementation on lipid peroxidation, a measure of oxidative stress, and
      viral load in humans. DESIGN: A randomized placebo-controlled, double-blind
      study. METHODS: Forty-nine HIV-positive patients were randomized to receive
      supplements of both DL-alpha-tocopherol acetate (800 IU daily) and vitamin C
      (1000 mg daily), or matched placebo, for 3 months. Plasma antioxidant
      micronutrient status, breath pentane output, plasma lipid peroxides,
      malondialdehyde and viral load were measured at baseline and at 3 months. New or
      recurrent infections for the 6-month period after study entry were also recorded.
      RESULTS: The vitamin group (n = 26) had an increase in plasma concentrations of
      alpha-tocopherol (P < 0.0005) and vitamin C (P < 0.005) and a reduction in lipid
      peroxidation measured by breath pentane (P < 0.025), plasma lipid peroxides (P <
      0.01) and malondialdehyde (P < 0.0005) when compared with controls (n = 23).
      There was also a trend towards a reduction in viral load (mean +/- SD changes
      over 3 months, -0.45 +/- 0.39 versus +0.50 +/- 0.40 log10 copies/ml; P = 0.1; 95%
      confidence interval, -0.21 to -2.14). The number of infections reported was nine
      in the vitamin group and seven in the placebo group. CONCLUSION: Supplements of
      vitamin E and C reduce oxidative stress in HIV and produce a trend towards a
      reduction in viral load. This is worthy of larger clinical trials, especially in
      HIV-infected persons who cannot afford new combination therapies.

PMID- 9764784
TI  - The effect of protease inhibitors on weight and body composition in HIV-infected
      patients.
AB  - OBJECTIVES: To determine the nutritional changes that occur in HIV-infected
      patients receiving protease inhibitor (PI) therapy and to determine the effects
      of PI treatment on physical functioning and health perceptions in patients with
      HIV infection. DESIGN: Longitudinal data analysis of 38 patients from a large
      Nutrition and HIV cohort. METHODS: Patients were included if they had started PI
      therapy after enrollment in the cohort, if they had taken the drug for at least 4
      months without interruption and if data on weight, body composition and viral
      loads were available. RESULTS: Mean person-months of follow-up was 8.1 months
      before and 12.2 months after PI treatment. Weight (1.54 kg, P < 0.0001), body
      mass index (0.50 kg/m2, P < 0.0001), physical functioning (8.52 points, P =
      0.0006) and current health perception (6.7 points, P = 0.01) increased
      significantly, and the daily caloric intake increase was close to significance
      (915.5 kJ/day, P = 0.06), after treatment with PI. Lean body mass did not change.
      Patients who responded to PI therapy with decreased viral load (n = 28) had
      significantly greater weight gain per month than non-responders. CONCLUSIONS: PI
      therapy of HIV infection is associated with weight gain and improvement in
      quality of life indices. The weight gain is mainly in fat mass, with no change in
      lean body mass (skeletal muscle). Optimal therapy of HIV-infected patients with
      weight loss may require highly active antiretroviral therapy combined with an
      anabolic stimulus such as exercise, anabolic steroids or human growth hormone.

PMID- 9764786
TI  - Mycobacterium xenopi in HIV-infected patients: an emerging pathogen.
AB  - BACKGROUND: Mycobacterium xenopi is associated with pulmonary disease in patients
      with loss of local or general host defence. OBJECTIVES: To determine the
      occurrence of M. xenopi in our hospital during 1987-1992 and 1993-1996, as well
      as the association of M. xenopi with HIV infection in 1993-1996; to evaluate the
      clinical significance of M. xenopi in HIV-seropositive patients. DESIGN:
      Retrospective review of charts and classification of patients based on earlier
      definitions derived from the American Thoracic Society. SETTING: Tertiary
      hospital. PATIENTS: Patients with a positive isolate of M. xenopi from January
      1987 until December 1996. MAIN OUTCOME MEASURES: During 1993 1996, a significant
      increase in the number of patients with M. xenopi was found compared with 1987
      1992. Of 25 patients, 22 were HIV-seropositive. RESULTS: The HIV-seropositive
      patients were classified as having definite (n = 5), probable (n = 9) and
      unlikely disease (n = 8) due to M. xenopi. Symptoms, median CD4 cell count,
      treatment and outcome did not differ between these groups. CONCLUSIONS: M. xenopi
      is an emerging pathogen, especially in HIV-infected patients. The criteria of the
      American Thoracic Society for disease due to non-tuberculous mycobacteria do not
      seem applicable to M. xenopi in HIV-infected patients. We suggest that two
      positive cultures of M. xenopi and no other likely cause of symptoms present
      should be considered the criteria for diagnosis of M. xenopi disease in HIV
      infected patients.

PMID- 9764787
TI  - Taste and smell complaints in HIV-infected patients.
AB  - OBJECTIVES: To define the scope of taste and smell (chemosensory) complaints
      amongst HIV-infected persons in the study population; to evaluate the clinical
      factors associated with chemosensory complaints; and to determine the impact of
      chemosensory complaints on quality of life. DESIGN: Cross-sectional survey.
      SETTING: Tertiary care university medical center clinic. PARTICIPANTS: A total of
      207 HIV-infected patients. MAIN OUTCOME MEASURES: Chemosensory complaint score
      from taste and smell questionnaire and quality of life scores from the Medical
      Outcomes Study HIV Health Survey (MOS-HIV). RESULTS: A total of 144 patients
      (70%) reported chemosensory complaints, 91 (44%) reported both taste and smell
      complaints, 47 (23%) reported only taste complaints, and six (3%) reported only
      smell complaints. Many patients complained that drugs interfered with their sense
      of taste, or that medications tasted bad. Higher chemosensory complaint scores
      were associated with a greater number of medications taken, tobacco use, and hay
      fever. Patients with chemosensory complaints had significantly lower scores in
      all domains of the MOS-HIV than those without complaints. Quality of life as
      measured by the MOS-HIV was lower in patients with chemosensory complaints even
      after controlling for number of AIDS diagnoses, number of medications, CD4 cell
      count, and HIV-1 viral load. CONCLUSIONS: Chemosensory complaints were common in
      the patient population and were associated with a poor quality of life.
      Medications played an important role in chemosensory complaints. Measures to
      optimize taste and smell function may improve quality of life and medication
      adherence, and prevent complications such as inadequate oral intake,
      malnutrition, weight loss, and ultimately wasting.

PMID- 9764788
TI  - Antiretroviral drugs as a public health intervention for pregnant HIV-infected
      women in rural South Africa: an issue of cost-effectiveness and capacity.
AB  - OBJECTIVE: To estimate cost-effectiveness and capacity requirements for providing
      antiretroviral drugs to pregnant HIV-infected women in rural South Africa.
      SETTING: Hlabisa health district, where HIV prevalence among pregnant women was
      26.0% in 1997. METHODS: Calculation of the number of paediatric HIV infections
      averted under three scenarios, and their cost. No intervention was compared with
      scenario A (zidovudine delivered within current infrastructure), scenario B
      (zidovudine delivered through enhanced infrastructure), and scenario C (short
      course zidovudine plus lamivudine delivered through enhanced infrastructure).
      Cost-effectiveness was defined as cost per infection averted and cost per
      potential life-year gained. Capacity was determined in terms of staff and
      infrastructure required to effectively implement the scenarios. RESULTS: With no
      intervention, 657 paediatric HIV infections were projected for 1997. In scenario
      A this could be reduced by 15% at a cost of US$ 574 825, in scenario B by 42% at
      US$ 1520770, and in scenario C by 47% at US$ 764901. In scenario C, drugs
      accounted for 76% of costs, whereas additional staff accounted for 18%. Cost per
      infection averted was US$ 2492 and cost per potential life-year gained
      (discounted at 3%) was US$ 88. Cost of scenario C was equivalent to 14% of the
      1997 district health budget. At least 12 extra counsellors and nurses and one
      laboratory technician, together with substantial logistical and managerial
      support, would be needed to deliver an effective intervention. CONCLUSION:
      Although antiretrovirals may be relatively cost-effective in this setting, the
      budget required is currently unaffordable. Developing the capacity required to
      deliver the intervention would pose both a major challenge, and an opportunity,
      to improve health services.

PMID- 9764789
TI  - Pneumococcal vaccination in HIV-1-infected adults in Uganda: humoral response and
      two vaccine failures.
AB  - OBJECTIVES: To assess the feasibility of establishing a pneumococcal vaccine
      trial among HIV-1-infected adults in Uganda and to characterize their responses
      to 23-valent pneumococcal polysaccharide vaccine. DESIGN: An open-label pilot
      trial to assess recruitment and compliance of HIV-1-infected adults in Uganda to
      vaccination and to determine the immunogenicity of the vaccine. SETTING: A
      community clinic for HIV-1-infected adults in Entebbe, Uganda. METHODS: Levels of
      capsule-specific IgG to four common vaccine capsular serotypes were measured
      before vaccination and 1 month after vaccination. Subsequent rates of disease
      episodes and deaths, and immunologic responses in two vaccine failures, were
      followed. RESULTS: One month after-vaccination, both HIV-1-infected (n = 77) and
      seronegative control subjects (n = 10) demonstrated a significant rise in capsule
      specific immunoglobulin G (IgG) for three of four serotypes tested, but levels
      were significantly lower among HIV-1-infected patients. In 149 patient-years of
      follow-up, two (2.6%) developed pneumococcal pneumonia, one bacteremic with
      serotype 1 and one non-bacteremic with serotype 13, a non-vaccine serotype; both
      patients showed inadequate killing of the organism in vitro. In this same follow
      up period, 29 (38%) patients died. CONCLUSION: HIV-1-infected adults in Uganda
      are at high risk of pneumococcal disease and show a significant but suboptimal
      response to pneumococcal vaccine. Although reliable recruitment and follow-up of
      vaccinees is feasible, evaluation of vaccine efficacy may be compromised by
      limited responses to common vaccine serotypes, an unknown incidence of disease
      with non-vaccine serotypes, and a high rate of mortality unrelated to
      Streptococcus pneumoniae infection.

PMID- 9764790
TI  - Effects of age at seroconversion and baseline HIV RNA level on the loss of CD4+
      cells among persons with hemophilia. Multicenter Hemophilia Cohort Study.
AB  - OBJECTIVE: To assess the impact of age at seroconversion and HIV RNA level in
      serum during early chronic infection on the initial values and subsequent trends
      (slopes) of CD4+ lymphocyte counts. DESIGN AND METHODS: In a cohort of 137 HIV-1
      positive hemophiliacs with well-estimated dates of seroconversion, baseline HIV
      RNA level was measured by reverse transcription PCR in serum specimens collected
      12-36 months after the estimated date of seroconversion. Baseline values, 24
      months after seroconversion, and slopes of CD4+ lymphocyte counts by age and HIV
      RNA quartile were examined by fitting random effects models that allowed for
      intrasubject variability. RESULTS: Both age at seroconversion and HIV RNA level
      were associated with the CD4+ lymphocyte count at baseline and its subsequent
      slope. The baseline median CD4+ lymphocyte count was 620 x 10(6)/l. Within each
      HIV RNA quartile, the median CD4+ cell count of the oldest subjects (age 30-58
      years) was about 200 x 10(6)/l lower and at least 350 x 10(6)/l lower than the
      median counts of the younger (age 11-29 years) and youngest (age 2-10 years)
      subjects, respectively. Within each age-group, the median CD4+ cell count
      differed by about 200 x 10(6)/l between subjects in the lowest compared with the
      highest HIV RNA quartiles. The mean slope of the CD4+ lymphocyte count after
      month 24 was linear on the square-root scale, steeper in children, and did not
      vary significantly by baseline HIV RNA quartile. There was large variation
      between subjects that was unexplained by differences in age and HIV RNA level.
      CONCLUSIONS: By 24 months after HIV seroconversion, the oldest subjects and those
      with the highest HIV RNA levels during early chronic infection had experienced
      the most severe depletion of CD4+ cells. Subsequent declines in CD4+ cells varied
      little by early chronic HIV RNA level or age.

PMID- 9764791
TI  - Bacterial vaginosis and disturbances of vaginal flora: association with increased
      acquisition of HIV.
AB  - BACKGROUND: Cross-sectional studies suggest an association between bacterial
      vaginosis (BV) and HIV-1 infection. However, an assessment of a temporal effect
      was not possible. OBJECTIVES: To determine the association of BV and other
      disturbances of vaginal flora with HIV seroconversion among pregnant and
      postnatal women in Malawi, Africa. DESIGN: Longitudinal follow-up of pregnant and
      postpartum women. METHODS: Women attending their first antenatal care visit were
      screened for HIV after counselling and obtaining informed consent. HIV
      seronegative women were enrolled and followed during pregnancy and after
      delivery. These women were again tested for HIV at delivery and at 6-monthly
      visits postnatally. Clinical examinations and collection of laboratory specimens
      (for BV and sexually transmitted diseases) were conducted at screening and at the
      postnatal 6-monthly visits. The diagnosis of BV was based on clinical criteria.
      Associations of BV and other risk factors with HIV seroconversion, were examined
      using contingency tables and multiple logistic regression analyses on antenatal
      data, and Kaplan-Meier proportional hazards analyses on postnatal data. RESULTS:
      Among 1196 HIV-seronegative women who were followed antenatally for a median of
      3.4 months, 27 women seroconverted by time of delivery. Postnatally, 97
      seroconversions occurred among 1169 seronegative women who were followed for a
      median of 2.5 years. Bacterial vaginosis was significantly associated with
      antenatal HIV seroconversion (adjusted odds ratio = 3.7) and postnatal HIV
      seroconversion (adjusted rate ratio = 2.3). There was a significant trend of
      increased risk of HIV seroconversion with increasing severity of vaginal
      disturbance among both antenatal and postnatal women. The approximate
      attributable risk of BV alone was 23% for antenatal HIV seroconversions and 14%
      for postnatal seroconversions. CONCLUSIONS: This prospective study suggests that
      progressively greater disturbances of vaginal flora, increase HIV acquisition
      during pregnancy and postnatally. The screening and treating of women with BV
      could restore normal flora and reduce their susceptibility to HIV.

PMID- 9764792
TI  - Declining HIV-2 prevalence and incidence among men in a community study from
      Guinea-Bissau.
AB  - OBJECTIVE: To assess the present level of HIV-2 infection in an adult population
      in Bissau and to evaluate sex and age-specific changes in HIV-2 prevalence and
      incidence between 1987 and 1996. DESIGN AND METHODS: Sex and age-specific changes
      in HIV-2 prevalence were evaluated comparing a survey from 1987 in a sample of
      100 houses with a survey performed in 1996 in an independent sample of 212 houses
      from the same study area. HIV-2 incidence rates were examined in an adult
      population (age > or = 15 years) from 100 randomly selected houses followed with
      four consecutive HIV serosurveys from 1987 to 1996. RESULTS: The HIV-2 prevalence
      in 1996 was 6.8% (men, 4.7%; women, 8.4%). Compared with the 1987 survey there
      was a significant decrease in prevalence among men [age-adjusted relative risk
      (RR), 0.50; 95% confidence interval (CI), 0.31-0.83], whereas it remained
      unchanged in women (RR, 1.00; 95% CI, 0.67-1.48). The male-to-female RR decreased
      from 0.99 (95% CI, 0.61-1.61) in 1987 to 0.51 (95% CI, 0.34-0.76) in 1996. The
      overall annual incidence rate was 0.54 per 100 person-years of observation (PYO),
      being higher in women (0.72 per 100 PYO) than in men (0.31 per 100 PYO). With the
      observation time divided into an early and a late period, there was a decrease in
      incidence with time among men (0.66 to 0.00 per 100 PYO), but no major change
      among women (0.59 to 0.85 per 100 PYO). The two trends differed significantly (P
      = 0.03). We observed a higher annual incidence rate amongst older women aged > 44
      years (1.77 per 100 PYO) than among younger women (0.55 per 100 PYO; P = 0.05).
      CONCLUSION: There are no signs of an epidemic spread of HIV-2 in Bissau even
      though the HIV-1 prevalence is increasing rapidly. A significant reduction in the
      male HIV-2 prevalence and incidence rates has resulted in a major shift in the
      pattern of spread of HIV-2, from being equally distributed to being predominantly
      a female infection. Currently, older women in particular seem to have a high risk
      of getting infected.

PMID- 9764793
TI  - Highly active antiretroviral therapy leads to a significant but delayed increase
      of CD45RA+ T-helper cells.

PMID- 9764794
TI  - Complete regression of AIDS-related Kaposi's sarcoma-associated human herpesvirus
      8 during therapy with indinavir.

PMID- 9764795
TI  - Herpes zoster infection in HIV-seropositive patients associated with highly
      active antiretroviral therapy.

PMID- 9764796
TI  - Progressive multifocal leukoencephalopathy following initiation of highly active
      antiretroviral therapy.

PMID- 9764797
TI  - Acute hepatitis in HIV-infected patients during ritonavir treatment.

PMID- 9764798
TI  - Bacterial lipopolysaccharide is a potent inhibitor of HIV-1 replication in T
      lymphocytes and macrophages.

PMID- 9764799
TI  - Use of highly sensitive assays for the evaluation of post-exposure HIV
      prophylaxis.

PMID- 9764800
TI  - Performance of an ultrasensitive assay to test undetectable viral load specimens
      using the branched DNA assay.

PMID- 9764801
TI  - Comparison of zidovudine phosphorylation in lymph nodes and peripheral blood
      mononuclear cells in HIV-infected patients. DATRI 012 Study Group.

PMID- 9764802
TI  - Increased susceptibility to HIV-1 infection of peripheral blood mononuclear cells
      from chronically immune-activated individuals.

PMID- 9764803
TI  - Effect of natural interferon-beta on the growth of melanoma cell lines.
AB  - Malignant melanoma is one of the fulminant skin cancers. The 5-year survival of
      patients with stage III (N0, N1) malignant melanoma treated with multi-agent
      chemoimmunotherapy, including natural interferon-beta (nIFNbeta), was found in
      our department to be better than that of patients treated with other forms of
      therapy. In order to study the effects of nIFNbeta on melanoma, the growth
      inhibition effect of nIFNbeta was assessed in vitro using the melanoma cell
      lines, MM8.1, MM28, MM33.1, Bowes and A375-2. The growth of these cell lines was
      inhibited by nIFNbeta. Incorporation of [3H]thymidine and [3H]uridine was also
      inhibited by nIFNbeta in a dose-dependent manner. Apoptosis was demonstrated
      using the TUNEL method in melanoma cell lines cocultured with nIFNbeta. Results
      showed that nIFNbeta had direct killer activity on melanoma cell lines.

PMID- 9764804
TI  - The PTEN tumour suppressor gene and malignant melanoma.
AB  - A candidate tumour suppressor gene, PTEN, has recently been identified within
      chromosome 10q23, the locus of the Cowden syndrome/Lhermitte Duclos disease
      susceptibility gene. Cowden disease is an autosomal dominant cancer
      predisposition syndrome associated with tumours of the breast, thyroid and, less
      frequently, malignant melanoma. Based on the identification of mutations in
      sporadic breast, brain and prostate tumours, we decided to examine the potential
      role of PTEN in sporadic malignant melanoma. Frozen tissue from primary cutaneous
      melanomas (n = 23) and metastases (n = 17) were microdissected, and
      microsatellite markers D10S541 and D10S547, flanking the gene on both sides, were
      used to search for loss of heterozygosity (LOH) in the PTEN gene locus. To
      identify mutations within the putative tumour suppressor gene, we performed
      single strand conformation polymorphism (SSCP) analysis using intronic primers to
      amplify exons 5, 6, 7 and 8 of the PTEN gene. No LOH was detected using the
      polymorphic markers D10S541 and D10S547. SSCP analysis revealed no aberrant bands
      in the tumour specimen. Our results suggest that the PTEN gene does not play a
      major role in the initiation and progression of melanoma.

PMID- 9764805
TI  - Positive association between cytoskeletal changes, melanoma cell attachment and
      invasion in vitro.
AB  - The literature concerning cytoskeletal changes and metastatic progression is
      unresolved, some studies suggesting a positive association between the ability of
      cells to organize their cytoskeleton and others suggesting an inverse
      correlation. In an attempt to learn more about cytoskeletal changes and the
      ability of melanoma cells to interact with extracellular matrix proteins we
      examined the effects of pharmacological manipulation of cell attachment and cell
      invasion through fibronectin on levels of F-actin and vimentin in a highly
      metastatic cutaneous melanoma cell line (A375-SM cells). Additionally, we
      examined whether any correlation existed between the levels of the cytoskeletal
      proteins and subpopulations of the cell line of varying invasive ability. We
      report that agents which reduced cell attachment to plastic and invasion through
      fibronectin in vitro (tamoxifen, N-desmethyltamoxifen and 17beta-oestradiol)
      caused increases in levels of F-actin and vimentin, whereas agents which did not
      affect attachment or invasion (4-hydroxytamoxifen and dihydrotestosterone) had
      little or no effect on the cytoskeletal proteins. In contrast, however, those
      cells which were most effective at invading through fibronectin were
      significantly better at acutely increasing their levels of F-actin and vimentin
      than less invasive cells. We speculate that the ability to rapidly and possibly
      reversibly alter the cytoskeleton might be associated with metastatically
      successful cells in vivo.

PMID- 9764806
TI  - Sensitivity of human melanoma cells to oestrogens, tamoxifen and quercetin: is
      there any relationship with type I and II oestrogen binding site expression?
AB  - We investigated the effect of oestrogens, anti-oestrogens and flavonoids on the
      growth of a human melanoma cell line (SK-Mel-28) and, at the same time, the
      presence of both type I oestrogen receptors (ERs) and type II oestrogen binding
      sites (type II EBS) to gain a fuller picture of the relationship between melanoma
      cell proliferation and receptor status. 17beta-Oestradiol (E2) and the flavonoid
      quercetin (Q) produced a marked inhibition of proliferation, but only at the
      highest dose used (10(-5) M) and only when added daily to the medium.
      Diethylstilboestrol (DES) (10(-5) M) was effective in inhibiting cell growth when
      the medium was renewed every 3 days and produced a more pronounced reduction when
      added daily to the medium. Tamoxifen (TAM) inhibited cell proliferation at a dose
      starting from 10(-7) M when the medium was renewed every 3 days. When added daily
      to the medium, it did not induce a greater inhibitory effect and it was cytotoxic
      at 5 x 10(-6) M and 10(-5) M. The antiproliferative effect of E2, DES and Q did
      not seem to be dependent on their interaction with ERs, which were minimally
      detected in SK-Mel-28 in both immunocytochemical and biochemical assays. Our
      model revealed, through a biochemical assay, a large number of type II EBSs which
      could be involved in the anti-oestrogen action, but this does not exclude the
      involvement of other mechanisms. Finally, TAM (10(-5) M) appeared to reduce the
      activity of the DNA repair enzyme O6-alkylguanine-DNA alkyltransferase, an effect
      that could be interesting from the point of view of the therapeutic efficacy of
      alkylating agents.

PMID- 9764807
TI  - Effect of prostaglandin A1 on proliferation and telomerase activity of human
      melanoma cells in vitro.
AB  - Previous studies have shown that cyclopentenone prostaglandins are endowed with
      antitumour activity in various murine and human tumour models. In the present
      investigation four human melanoma cell lines were treated with graded
      concentrations (4-16microg/ml) of prostaglandin A1 (PGA1) for 24 or 48 h in
      vitro. At the end of the treatment, cell proliferation (measured in terms of DNA
      synthesis) and telomerase activity were determined. The results showed that PGA1
      induced concentration-dependent inhibition of DNA synthesis at 48 h but not at 24
      h in SK-MEL-28 cells. In contrast, marked inhibition of telomerase activity was
      detected after only 24 h of PGA1 treatment. Moreover, after 48h of treatment with
      the agent, inhibition of telomerase was more pronounced than inhibition of cell
      proliferation. Additional studies performed with three freshly generated melanoma
      cell lines confirmed that PGA1 produced early inhibition of cell growth
      accompanied by marked impairment of telomerase activity. These results suggest
      that PGA1 could be of potential value as antitumour agent, on the basis of two
      distinct mechanisms: direct cytostatic/cytotoxic effects on melanoma cells, and
      inhibitory activity on a tumour-associated enzymatic function (i.e. telomerase)
      that is responsible for cancer cell immortality.

PMID- 9764808
TI  - Modifications of the antioxidant enzymes in relation to chromosome imbalances in
      human melanoma cell lines.
AB  - Five human melanoma cell lines were investigated for their antioxidant
      activities. These metabolic data were correlated with cytogenetic analysis giving
      the relative numbers of chromosomes or chromosomal segments carrying the gene
      encoding for each enzyme. Particular attention was focused on the expression of
      superoxide dismutase 2 (SOD2), whose gene, located on the long arm of chromosome
      6 (6q), has been proposed as a tumour suppressor gene. The activity of
      glutathione peroxidase (GPX), glutathione reductase (GSR) and catalase appeared
      to be unrelated to the relative number of 3q, 8p and 11p arms which,
      respectively, carry their encoding genes. GPX activity paralleled that of total
      SOD activity, and GSR variations followed those of GPX, suggesting possible
      metabolic regulation. Both the activity and the amount of SOD1 immunoreactive
      protein correlated with the number of chromosomes 21, suggesting a gene dosage
      effect. The three cell lines with deletions of the 6q arm had lower SOD2 activity
      and less immunoreactive protein than the two cell lines without 6q deletion. In
      addition, they demonstrated high thymidine kinase and thymidylate synthetase
      activities, which are directly linked to the cell proliferation rate. These
      results strengthen the hypothesis that SOD2 has a function as a tumour suppressor
      gene, but also suggest that the expression of other antioxidant enzymes might be
      altered in human melanomas.

PMID- 9764809
TI  - Melan A/MART-1 immunoreactivity in formalin-fixed paraffin-embedded primary and
      metastatic melanoma: frequency and distribution.
AB  - Monoclonal antibody (MAb) A103 specifically detects Melan A/MART-1 protein
      expression. Melan A/MART-1-derived peptides are recognized by CD8+ T-cells and
      are used in immunotherapy. We examined formalin-fixed paraffin-embedded tissue
      from 57 melanomas (34 primary, 23 metastatic) and 39 control cases (junctional,
      dermal, compound, Spitz, Reed and balloon-cell naevi) using the alkaline
      phosphatase and anti-alkaline phosphatase immunochemical method after antigen
      retrieval. Immunoreactivity was rated as low, medium or high, and staining
      pattern as homogeneous or heterogeneous. Staining with MAb A103 showed a
      sensitivity of 88% for melanoma, with a very high specificity for melanocytic
      cells. Immunopositivity decreased along with clinical stage, with stage I showing
      100%, stage II 88%, stage III 90% and stage IV 75% immunoreactivity. Staining
      changed from an exclusively homogeneous pattern in the early clinical stages to a
      more heterogeneous pattern in the later stages. Melanocytic control tissues
      consisting of naevi of different subtypes all showed weak to moderate homogeneous
      immunoreactivity, with polarity towards the epidermis. Analysis of short-term
      melanoma cell cultures using reverse transcription-polymerase chain reaction (RT
      PCR) enzyme-linked immunosorbent assay (ELISA) demonstrated mRNA expression in
      only one third of the originally immunopositive tumours, suggesting rapid mRNA
      expression loss in culture. MAb A103 allows the detection of melanoma-associated
      Melan A/MART-1 protein expression in routine archival tissue and thus enables the
      profiling of melanomas suited for immunotherapy approaches involving Melan A/MART
      1 derived epitopes.

PMID- 9764810
TI  - TAP prefers to transport melanoma antigenic peptides which are longer than the
      optimal T-cell epitope: evidence for further processing in the endoplasmic
      reticulum.
AB  - Many melanoma epitopes are presented to cytotoxic T-lymphocytes (CTLs) by major
      histocompatibility complex (MHC) class I molecules, and it is reasonable to
      expect that the epitopes would be good substrates for the transporter associated
      with antigen processing (TAP), as TAP plays a major role in the transport of
      peptides into the endoplasmic reticulum (ER) for binding to MHC class I
      molecules. However, we have previously shown that several melanoma-associated
      epitopes, such as those derived from tyrosinase, gp100, MAGE-1 and MAGE-2
      antigens, are in fact poor substrates for TAP. During the process of determining
      why these epitopes were capable of eliciting a strong CTL response, yet were poor
      substrates for TAP, it was observed that the epitopes possessed amino acids at
      their N-terminus that were deleterious for TAP binding as described for the
      peptide-binding motif for human TAP. We therefore postulated that the epitopes
      were transported by TAP as longer precursor molecules, and then trimmed in the ER
      to the appropriate size for presentation to T-cells. In an effort to test this
      hypothesis we synthesized a set of peptides, derived from the tyrosinase
      (YMNGTMSQV) and MAGE-1 (EADPTGHSY) epitopes, which possess N-terminal extensions
      of up to four amino acids. We show here that the longer peptides are indeed
      transported into the ER at a significantly higher level than the original
      epitopes. The data indicate that the longer melanoma-associated peptides are the
      preferred substrates for TAP, and further support the notion that peptides can be
      trimmed at the N-terminus in the ER during antigen processing.

PMID- 9764811
TI  - Detection of recurrent malignant melanoma with 99mTc-MIBI scintigraphy.
AB  - Initial reports suggest that 99mTc-methoxyisobutylisonitrile (MIBI) scanning may
      be of clinical value in staging patients with malignant melanoma. We carried out
      a study to evaluate the potential of this technique in the detection of recurrent
      disease. Whole-body 99mTC-MIBI scans were performed in 81 patients with a history
      of a surgically excised MM: 28 with known recurrent lesions and 53 during follow
      up without evidence of disease. Images started 10 min post-injection, using a
      dose of 740 MBq. Diagnoses were confirmed by cytological/histological examination
      or at least one conventional imaging modality. Blinded interpretations of the
      MIBI scans were performed. Whole-body MIBI scanning correctly detected 68 (92%)
      of 74 metastatic lesions in the following sites: regional lymph nodes (n=23), non
      regional lymph nodes (n=10), skin (n=16), brain/cerebellum (n=6), lung (n=8),
      bone (n=4) and breast (n=1). The technique failed to detect three subcutaneous
      regressive lesions (< 1 cm), one liver metastasis, one spleen metastasis and a
      case of multiple small lesions of the duodenal mucous membrane. In 14 patients
      the procedure detected previously unknown metastatic lesions. These results
      suggest that 99mTc-MIBI scanning is an effective imaging modality for whole-body
      screening of metastatic disease in malignant melanoma patients with the potential
      to influence treatment planning.

PMID- 9764812
TI  - Multiple primary melanomas: analysis of 49 cases.
AB  - Development of multiple primary melanomas is a rare but well recognized disease,
      with an estimated incidence ranging from 1.75% to 8.5% in several series. The
      clinical, histological and epidemiological characteristics of 49 patients,
      identified from 2470 with histologically confirmed melanoma, are described in
      this study. Thirty-five of these patients had two primary melanomas, 11 had three
      melanomas and three had four, five and six melanomas, respectively. Diagnosis was
      concurrent in 22 patients (45%); in the remaining cases the median time interval
      between the first and second melanoma was 22.6 months and the longest interval
      was 21.5 years. The mean Breslow's thickness decreased significantly (P < 0.001)
      from the first melanoma to the second and third lesion. The multiple melanoma
      patients had a higher percentage of subjects over 70 years of age or with lentigo
      maligna melanoma than single melanoma patients. The mean follow-up time was 12
      years (range 4 23 years). The 5-year survival rate from first melanoma excision
      (83%) does not differ from that of patients with a single melanoma. In
      conclusion, the presence of multiple primary melanomas does not appear to be a
      negative prognostic factor; our data show the importance of close follow-up in
      melanoma patients in order to detect not only metastases, but also subsequent
      primaries in their earliest phases.

PMID- 9764813
TI  - Syndrome of inappropriate secretion of antidiuretic hormone in a patient affected
      by metastatic melanoma.
AB  - The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is
      characterized by hyponatraemia due to water retention resulting from the
      persistent release of antidiuretic hormone (vasopressin). It may occur in a
      variety of malignant and non-malignant conditions, in particular in association
      with oat cell carcinoma, pulmonary and cerebral diseases. We report the case of a
      male patient affected by melanoma of the right temporal region with brain
      metastasis who developed acute headache, drowsiness, nausea, vomiting and
      pathological reflexes. Clinical and laboratory investigations led us to the
      diagnosis of SIADH. Restriction of fluid intake obtained a good clinical
      improvement with normalization of laboratory alterations; after 2 months the
      patient experienced a new episode of SIADH which was promptly treated. As
      melanoma has been occasionally observed in association with SIADH it should be
      included in the list of tumours that can cause this particular syndrome.

PMID- 9764814
TI  - Phenotypic markers, sunlight-related factors and sunscreen use in patients with
      cutaneous melanoma: an Austrian case-control study.
AB  - Sunscreens have been advocated to prevent burning in the hope that this will
      decrease the chance of developing melanoma. In a single-centre case-control study
      in Styria, Austria, we examined the risk of cutaneous malignant melanoma in
      relation to phenotypic markers, sunlight-related factors and sunscreen use. In
      total, 193 melanoma patients and 319 control subjects answered a comprehensive
      questionnaire regarding phenotypic markers, a variety of sunlight-related factors
      and sunscreen use. Risk factors for melanoma were examined through the use of
      unconditional logistic regression analysis, controlling for age and sex.
      Screening for confounding factors was done by forward and backward elimination of
      non-significant variables (P < 0.05). The resulting set of factors were
      investigated further for effect modification by introducing interactions into the
      model. The factor most significantly associated with increased melanoma risk was
      the use of sunscreens. Subjects who often used sunscreens had an increased odds
      ratio (OR) of 3.47 (95% confidence interval [CI]1.81-6.64) compared with subjects
      who never used sunscreens (P = 0.001), after adjustment for sex, age and other
      significant sunlight-related factors. Skin colour and higher numbers of sunbaths
      were significant protective factors. Subjects with medium skin colour had an
      adjusted OR of 0.63 (95% CI 0.41-0.99) compared with subjects with light skin
      colour (P = 0.0022). Subjects who took more than 30 sunbaths per year and
      subjects who took 20-30 sunbaths per year had, in the absence of sunburn(s), a
      decreased OR of 0.09 (95% CI 0.02-0.39) and 0.28 (95% CI 0.13-0.64),
      respectively, compared with subjects who took less than 20 sunbaths per year (P =
      0.0002). However, sunbaths had no protective value when they were associated with
      sunburns. Although we cannot exclude the presence of an unknown confounding
      factor, our results suggest that the use of sunscreens does not help prevent
      melanoma.

PMID- 9764815
TI  - Effective combined immunochemotherapy with dinitrochlorobenzene and fotemustine
      in skin and brain metastases of melanoma.

PMID- 9764816
TI  - Cancer phenotype correlates with constitutional TP53 genotype in families with
      the Li-Fraumeni syndrome.
AB  - The Li-Fraumeni cancer predisposition syndrome is associated with germline TP53
      mutations in the majority of families. We have investigated cancer incidence in
      34 Li-Fraumeni families, according to their constitutional TP53 mutation status.
      Families with germline missense mutations in the core DNA binding domain showed a
      more highly penetrant cancer phenotype than families with other TP53 mutations or
      no mutation. Cancer phenotype in families carrying such mutations was
      characterized by a higher cancer incidence and earlier ages at diagnosis,
      especially of breast cancer and brain tumours, compared with families carrying
      protein truncating or other inactivating mutations (P=0.03 for all cancers,
      P=0.006 for breast cancers, P=0.05 for brain tumours). Proband cancers showed
      significantly younger ages at diagnosis in those with missense mutations in the
      DNA binding domain than in those with protein inactivating mutations (P=0.031).
      In individuals with the former type of mutation, there was a significantly lower
      proportion of tumours which showed loss of the wild-type TP53 allele (P=0.004).
      These results are consistent with observations in experimental systems which
      demonstrate that certain mutations exhibit gain of function and/or dominant
      negative properties. Our results support an enhanced oncogenic potential for such
      mutations in human populations.

PMID- 9764817
TI  - Bax cleavage is mediated by calpain during drug-induced apoptosis.
AB  - The anti-apoptotic molecule Bcl-2 is located in the mitochondrial and endoplasmic
      reticulum membranes as well as the nuclear envelope. Although its location has
      not been as rigorously defined, the pro-apoptotic molecule Bax appears to be
      mainly a cytosolic protein which translocates to the mitochondria upon induction
      of apoptosis. Here we identify a protease activity in mitochondria-enriched
      membrane fractions from HL-60 cells capable of cleaving Bax which is absent from
      the cytosolic fraction. Bax protease activity is blocked in vitro by cysteine
      protease inhibitors including E-64 which distinguishes it from all known caspases
      and granzyme B, both of which are involved in apoptosis. Protease activity is
      also blocked by inhibitors against the calcium-activated neutral cysteine
      endopeptidase calpain. Partial purification of the Bax protease activity from HL
      60 cell membrane fractions by column chromatography revealed that a calpain-like
      activity was the protease responsible for Bax cleavage. In addition, purified
      calpain enzymes cleaved Bax in a calcium-dependent manner. Pretreatment of HL-60
      cells with the specific calpain inhibitor calpeptin effectively blocked both drug
      induced Bax cleavage and calpain activation, but not PARP cleavage or cell death.
      These results suggest that calpains and caspases are activated during drug
      induced apoptosis and that calpains, along with caspases, may be involved in
      modulating cell death by acting selectively on cellular substrates.

PMID- 9764818
TI  - Grb2 binding to the different isoforms of Ret tyrosine kinase.
AB  - The RET proto-oncogene encodes two isoforms of a receptor tyrosine kinase which
      plays a role in neural crest and kidney development. Ret ligands have been
      recently identified as the neuron survival factor GDNF (Glial-Derived
      Neurotrophic Factor) and Neurturin. Somatic rearrangements of RET, designated
      RET/PTCs, have been frequently detected in papillary thyroid carcinomas. In
      addition, distinct germ-line mutations of RET gene have been associated with the
      inherited cancer syndromes MEN (Multiple Endocrine Neoplasia) 2A, 2B and FMTC
      (Familial Medullar Thyroid Carcinomas) as well as with the congenital megacolon
      or Hirschsprung's disease, thus enlightening a significant role of this receptor
      gene in diverse human pathologic conditions. In this study, by performing
      classical inhibition experiments using synthetic phosphopeptides and by site
      directed mutagenesis of the putative docking site, we have determined that for
      Grb2 the latter is provided by the tyrosine 620 of Ret/ptc2 long isoform
      (corresponding to Tyr 1096 on proto-Ret). However, in intact cells, the
      interaction of Grb2 with the two short and long Ret isoforms expressed separately
      is of similar strength, thus suggesting that Ret short isoform interaction with
      Grb2 could be mediated not only by Shc but also by a molecule that binds
      preferentially to this isoform. This possibility is supported by the evidence
      that the mutant Ret/ptc2Y620F long isoform displays a weak coimmunoprecipitation
      with Grb2 and that this mutant, lacking the docking site for Grb2 but owing all
      the others phosphotyrosines, surprisingly displays a reduced transforming
      activity compared to that of the two WTs oncogenes. We thus conclude that in
      intact cells both Ret isoforms bind to Grb2, although with different modalities.
      In addition, the present results are in agreement with the possibility that
      different signal transduction pathways are associated with the two isoforms of
      Ret.

PMID- 9764819
TI  - Stress-induced secretion of growth inhibitors: a novel tumor suppressor function
      of p53.
AB  - p53 tumor suppressor gene controls cell response to a variety of stresses
      inducing growth arrest or apoptosis in damaged cells. It largely determines the
      sensitivity of tumor and normal cells to radiation and chemotherapy, and,
      therefore, defines both the efficacy and limitations of anti-cancer treatment. To
      determine molecular mechanisms of p53-dependent stress response in normal tissues
      we identified and compared the spectra of radiation-responsive genes in cells of
      different origin and p53 status using a cDNA array hybridization technique. The
      majority of genes identified were p53-dependent and cell type specific. Several
      of the new p53 responders encode known secreted growth inhibitory factors. This
      suggests that p53, in addition to its intrinsic antiproliferation activity, can
      cause 'bystander effect' by inducing export of growth suppressive stimuli from
      damaged cells to neighboring cells. Consistently, a p53-dependent accumulation of
      factors, which causes growth inhibitory effects in a variety of cell lines, was
      found after gamma irradiation in the media from established and primary cell
      cultures and in the urine of irradiated mice. Moreover, p53-dependent factors
      released by normal human fibroblasts potentiated the cytotoxic effect of a
      chemotherapeutic drug on co-cultivated tumor cells. This suggests a previously
      unknown role for normal cells in chemo- and radiation therapy of cancer.

PMID- 9764820
TI  - The Tek/Tie2 receptor signals through a novel Dok-related docking protein, Dok-R.
AB  - Tek/Tie2 is an endothelial cell-specific receptor tyrosine kinase that has been
      shown to play a role in vascular development of the mouse. Targeted mutagenesis
      of both Tek and its agonistic ligand, Angiopoietin-1, result in embryonic
      lethality, demonstrating that the signal transduction pathway(s) mediated by this
      receptor are crucial for normal embryonic development. In an attempt to identify
      downstream signaling partners of the Tek receptor, we have used the yeast two
      hybrid system to identify phosphotyrosine-dependent interactions. Using this
      approach, we have identified a novel docking molecule called Dok-R, which has
      sequence and structural homology to p62dok and IRS-3. Mapping of the
      phosphotyrosine-interaction domain within Dok-R shows that Dok-R interacts with
      Tek through a PTB domain. Dok-R is coexpressed with Tek in a number of
      endothelial cell lines. We show that coexpression of Dok-R with activated Tek
      results in tyrosine phosphorylation of Dok-R and that rasGAP and Nck
      coimmunoprecipitate with phosphorylated Dok-R. Furthermore, Dok-R is
      constitutively bound to Crk presumably through the proline rich tail of Dok-R.
      The cloning of Dok-R represents the first downstream substrate of the activated
      Tek receptor, and suggests that Tek can signal through a multitude of pathways.

PMID- 9764821
TI  - The C. elegans MDL-1 and MXL-1 proteins can functionally substitute for
      vertebrate MAD and MAX.
AB  - The genes of the myc/max/mad family play an important role in controlling cell
      proliferation and differentiation. We have identified the first homologues of the
      mad and max genes in the nematode C. elegans, which we have named mdl-1 and mxl-1
      respectively. Like the vertebrate MAD proteins, MDL-1 binds an E-box DNA sequence
      (CACGTG) when dimerized with MXL-1. However, unlike vertebrate MAX, MXL-1 can not
      form homodimers and bind to DNA alone. Promoter fusions to a GFP reporter suggest
      that these genes are coexpressed in posterior intestinal and post-mitotic
      neuronal cells during larval development. The coexpression in the posterior
      intestinal cells occurs before their final division at the end of the L1 stage
      and persists afterwards, demonstrating that mad and max expression can be
      correlated directly to the cell cycle state of an individual cell type. These
      data also show that mxl-1 is an obligate partner for mdl-1 in vivo and in vitro
      and indicate that these genes may play an important role in post-embryonic
      development. Finally, MDL-1 can suppress activated c-MYC/RAS-induced focus
      formation in a rat embryo fibroblast transformation assay. Like the vertebrate
      MAD protein, MDL-1 activity in suppressing transformation is dependent on a
      functional SIN3 interaction domain.

PMID- 9764822
TI  - Endogenous p53 regulation and function in early stage Friend virus-induced tumor
      progression differs from that following DNA damage.
AB  - Erythroleukemia induced by the anemia strain of Friend virus occurs in two
      stages. The first stage results in rapid expansion of pre-leukemic
      proerythroblasts (FVA cells) dependent on erythropoietin (Epo) for
      differentiation and survival in vitro. The second stage is characterized by
      emergence of erythroleukemic clones (MEL cells) which typically bear activation
      of the ets-oncogene, PU.1/spi.1, and loss of functional p53. We developed a
      Friend virus-sensitive, p53-deficient mouse model to investigate the biological
      advantage conferred by p53-loss during tumor progression. Here we report p53 was
      not required for cell survival or growth arrest during differentiation of FVA
      cells, nor was p53 required for induction of apoptosis upon Epo withdrawal.
      However, we detected induction of the p21Cip1 cyclin-dependent kinase inhibitor
      gene during differentiation, which was markedly enhanced in the presence of p53.
      p53-dependent expression of p21Cip1 occurred in the absence of an increase in p53
      mRNA and protein levels and was specific for p21Cip1, since expression of gadd45,
      mdm-2, cyclin G and bax were unaffected by p53. In contrast, treatment of FVA
      cells with DNA damaging agents led to rapid accumulation of p53 protein resulting
      in transcription of multiple p53-regulated genes, leading to either apoptosis or
      growth arrest, depending on the agent used. These data demonstrate that p53
      dependent activities during differentiation of preleukemic erythroblasts are
      distinct from those observed in response to genotoxic agents. We propose that
      enhancement of p53-dependent gene expression during differentiation may represent
      a tumor suppressor function which is necessary to monitor differentiation of
      preleukemic cells and which is selected against during tumor progression.

PMID- 9764823
TI  - Overexpression of fra-2 in transgenic mice perturbs normal eye development.
AB  - The major components of transcription factor AP-1 (Activator Protein 1) are
      encoded by the two families of genes related to the proto-oncogenes c-fos and c
      jun. The fos-related antigen-2 (fra-2) gene is the most recently described member
      of the Fos family. To determine the oncogenic potential of fra-2, transgenic mice
      were generated which over-express fra-2 in a number of tissues. No tumours were
      evident in any transgenic mice up to 18 months of age, although eye development
      was severely disrupted in these animals. Corneal abnormalities could be observed
      histologically as early as embryonic day 15.5 and eyelid fusion failed to occur.
      Adult eyes were characterized by generalized anterior segment dysgenesis similar
      to that previously reported in transgenic mice over-expressing transforming
      growth factor alpha (TGF alpha), and occasionally microphthalmia. Expression of
      fra-2 was shown to increase following TGF alpha treatment of cells in vitro,
      suggesting that AP-1 complexes containing Fra-2 contribute to TGF alpha
      signalling events.

PMID- 9764824
TI  - TSG101 is not mutated in lung cancer but a shortened transcript is frequently
      expressed in small cell lung cancer.
AB  - TSG101 is a candidate tumor suppressor gene whose deletion in NIH3T3 cells leads
      to spontaneous lung metastases in nude mice. Aberrant transcripts of TSG101 have
      been identified in 47% of primary breast carcinomas, without evidence of
      intragenic deletions at the TSG101 locus on 11p15. To investigate the possible
      role of TSG101 in lung cancer, which often shows 11p allele loss, we performed
      transcript analysis and mutational analysis of TSG101 in lung cancer cell lines.
      Reverse transcriptase RT-PCR and Northern analysis detected a common TSG101
      transcript, shortened because of an internal deletion, which was expressed
      simultaneously with the wild-type transcript in 89% of small cell lung cancer
      (SCLC) lines. In contrast, the wild-type transcript was expressed alone in normal
      tissues, primary non-small cell lung cancer (NSCLC) specimens, and the majority
      of NSCLC cell lines. Sequence of the shortened SCLC transcript was identical to
      that of the most common aberrant transcript identified in breast cancer,
      consisting of a deletion of exons 2-4 and part of 1 and 5. Southern analysis of
      SCLC lines expressing the shortened transcript did not detect any intragenic
      deletions. Single strand conformational polymorphism (SSCP) analysis and direct
      sequencing of TSG101 cDNAs also identified no mutations or deletions. These
      results suggest that TSG101 is not mutated in lung cancer but that aberrant
      splicing of TSG101 occurs in SCLC.

PMID- 9764825
TI  - Fli-1b is generated by usage of differential splicing and alternative promoter.
AB  - The proto-oncogene Fli-1, a member of Ets family is rearranged or activated
      through proviral integration in erythroleukemias, induced by Friends' Murine
      Leukemia Virus. The DNA binding domain (ETS domain) of Fli-1 is fused to the RNA
      binding domain of EWS by t(11q24:22q12) chromosomal translocation in Ewing's
      sarcoma and primitive neuroectodermal tumors. Screening of human cDNA libraries
      has identified two different 5'-termini and alternatively spliced forms of the
      human Fli-1 gene (Fli-1b), suggesting the possible existence of two independent
      promoters. The genomic sequence adjacent to the alternate exon of human Fli-1b
      gene shows functional promoter activity when cloned in promoter-less CAT
      expression vector and transfected into QT-6 cells. The transcription initiation
      (CAP) site and minimum promoter region necessary for function were localized. The
      5'-flanking regions of human Fli-1b and mouse Fli-1 show 80% homology suggesting
      conserved promoter regulatory elements. The Fli-1b 5'-flanking sequence lacks
      canonical TATA or CCAAT boxes but contains a partially conserved TATA-like
      sequence at position 242. Several transcription factor binding sequences like
      ATF/CREB, E2A-PBX1, EBP, PEA-3, ETS-2, Sp-1, c-Myc, TBP, GATA-1 and Oct-3 were
      conserved in the promoter sequence. Functional promoter assays revealed that Fli
      1b promoter shows very strong transcriptional activation compared to Fli-1
      promoter. We also showed that variant Fli-1b has transcriptional activation
      properties similar to those of Fli-1. Fli-1b and Fli-1 show differential
      expression in various hematopoietic cell lines. This differential expression and
      promoter activities of Fli-1 and Fli-1b suggests that several mechanisms are
      involved in Fli-1 gene regulation which are mediated by many transcription
      factors.

PMID- 9764826
TI  - Early G1 growth arrest of hybridoma B cells by DMSO involves cyclin D2 inhibition
      and p21[CIP1] induction.
AB  - Dimethylsulfoxide (DMSO) was shown to inhibit the proliferation of several B cell
      lines including Raji, Daudi, and SKW6-CL4 but the mechanisms involved in this
      growth arrest are still unclear. We show that in 7TD1 mouse hybridoma cells a
      DMSO-induced reversible G1 arrest involves inactivation of Rb kinases, cyclin
      D2/CDK4 and cyclin E/CDK2. This occurs by at least three distinct mechanisms.
      Inhibition of cyclin D2 neosynthesis leads to a dramatic decrease of
      cyclinD2/CDK4 complexes. This in turn enables the redistribution of p27[KIP1]
      from cyclin D2/CDK4 to cyclin E/CDK2 complexes. In addition, the simultaneous
      accumulation of p21[CIP1] entails increasing association with cyclin D3/CDK4 and
      cyclin E/CDK2. Thus, p21[CIP1] and p27[KIP1], act in concert to inhibit cyclin
      E/CDK2 activity which, together with CDK4 inactivation, confers a G1-phase
      arrest.

PMID- 9764827
TI  - PTCH gene mutations in invasive transitional cell carcinoma of the bladder.
AB  - LOH analysis suggests that multiple tumor suppressor genes play a role in the
      development of human TCC. The human homolog of the Drosophila PTCH was recently
      cloned and mapped to the BCNS locus on 9q22.3, a chromosomal region commonly
      deleted in TCCs. We first examined the steady state mRNA transcription of the
      PTCH, SMOH and GLI3 genes of the HH signal transduction pathway in TCC cell lines
      and normal urothelium. Normal urothelium and TCC cell lines express these three
      genes within the PTCH signal transduction pathway. We then screened for PTCH
      mutations in 'hot spot' exons 6, 8, 13 and 16 by PCR/SSCP analysis of genomic
      DNAs from 54 TCC tumor samples and control autologous peripheral blood
      lymphocytes. DNA sequence analysis confirmed TCC-specific mutations in two of 54
      patients (3.7%). These mutations resulted a single amino acid substitution and
      two frame shifts. One tumor had PTCH mutations in exon 16 as well as exon 13 and
      one tumor had a mutation in exon 13 alone. Both TCC tumors that contained PTCH
      mutations had a loss of heterozygosity at 9q. Although the PTCH protein has an
      unknown function in urothelial cells, the detection of the PTCH, SMOH and GLI3
      transcripts in normal urothelium and TCC cell lines and rare PTCH mutations in
      tumor samples suggest that the HH pathway may have a role in controlling the
      proliferation of urothelial cells and that PTCH mutations may contribute to the
      development of a subset of TCCs.

PMID- 9764828
TI  - p96, a MAPK-related protein, is consistently downregulated during mouse mammary
      carcinogenesis.
AB  - Differential display PCR [DD-PCR] was applied to identify mRNAs differentially
      expressed between two consecutive stages of an in vivo model of mouse mammary
      carcinogenesis. The extended life 12 [EL12] and transformed mammary 12 [TM12]
      outgrowths differ in morphology, ovarian hormone dependence, and tumorigenicity,
      yet the TM12 outgrowth arose spontaneously from the EL12 outgrowth. A fragment of
      the mouse p96 gene was identified using DD-PCR. The differential expression of
      p96 was confirmed using RNase protection assays. Examination of the RNA
      expression patterns of the p96 isoforms during normal mammary gland development
      showed high levels in the involuting mammary gland and in preneoplastic
      hyperplasias. In contrast, p96 isoform mRNA levels were consistently decreased in
      mammary tumors derived from the in vivo hyperplasias. Examination of p96 protein
      levels revealed a decrease in p96 protein in a number of mammary tumors as
      compared to their hyperplastic precursors further supporting the observations
      that p96 gene expression is consistently downregulated in mammary tumors. The
      functional activity of p96 protein has not been resolved, however the observation
      that p96 gene expression is downregulated in two different tumor systems (human
      ovarian tumors and mouse mammary tumors) warrants more extensive investigation on
      its role in normal and neoplastic cell growth.

PMID- 9764829
TI  - Decreased fibronectin expression in Met/HGF-mediated tumorigenesis.
AB  - The tyrosine kinase receptor Met and its ligand, hepatocyte growth factor
      (HGF)/scatter factor are involved in the etiology and progression of a number of
      human cancers. Coexpression of Met and HGF in mesenchymal cells increases the
      tumorigenic and metastatic potential of the cells. In the studies described here,
      we used differential display screening to identify changes in gene expression
      that are initiated by Met/HGF, and that may lead to these phenotypes. We learned
      that Met/HGF signaling resulted in greatly decreased fibronectin mRNA production
      in three different human and mouse tumor cell lines; these decreases in
      fibronectin mRNA were paralleled by decreases in fibronectin protein. We also
      found a progressive decrease in fibronectin in tumor explants and metastases
      derived from the Met/HGF transformed cells. The absence of fibronectin expression
      is a frequent cancer phenotype; our results indicate that decreases in
      fibronectin correlate with, but are not essential for, MetHGF/SF-mediated
      tumorigenesis.

PMID- 9764830
TI  - Frequent loss of heterozygosity and three critical regions on the short arm of
      chromosome 8 in ovarian adenocarcinomas.
AB  - Many chromosomal regions undergo loss of heterozygosity (LOH) in ovarian
      adenocarcinomas but few of the target regions have been finely mapped. One of the
      chromosome arms likely to harbour one or more tumour suppressor genes inactivated
      in ovarian cancer is the short arm of chromosome 8 which is frequently deleted in
      many other solid tumours. We have examined a large panel of microsatellite
      markers on 8p for LOH in 53 ovarian adenocarcinomas. LOH was observed in 27
      tumours (51%), with a significant trend towards a higher frequency of LOH in more
      advanced tumours. Detailed examination of nine tumours with partial deletions
      defined three regions of overlap, two in 8p23 and one in 8p22, which suggests
      that there might be as many as three tumour or metastasis suppressor genes on 8p
      which are inactivated during ovarian tumorigenesis. LOH on 8p was significantly
      associated with 9p LOH which suggests that inactivation of target genes on these
      chromosomes may be cooperative events.

PMID- 9764831
TI  - Pterins in human hair follicle cells and in the synchronized murine hair cycle.
AB  - Human dermal papilla cells (HDPC) express mRNA for the key enzymes for de novo
      synthesis/recycling and regulation of the pterin (6R)-L-erythro-5,6,7,8
      tetrahydrobiopterin (6BH4). HDPC had significantly higher enzyme activities and
      6BH4 levels in a comparative study with dermal fibroblasts, epidermal
      melanocytes, and keratinocytes under in vitro conditions. In addition, a
      significantly more rapid uptake of 14C-L-phenylalanine was demonstrated in HDPC
      compared with fibroblasts, whereas the differences in turnover to L-tyrosine were
      insignificant, suggesting a pooling of L-phenylalanine in HDPC. These results
      suggested that HDPC driven 6BH4 synthesis could be of major functional importance
      in the hair cycle. In order to follow this hypothesis in vivo, expression of
      enzyme activities and levels of the produced cofactor during the synchronized
      hair cycle were determined employing the murine model C57BL/6. These data
      revealed a significantly increased de novo synthesis for 6BH4 via GTP
      cyclohydrolase I concomitant with high levels of 6BH4, and the induction of
      phenylalanine hydroxylase activities during the telogen/early anagen stage (days
      0-1). Pterin levels and enzyme activities fall on day 3 and plateau during the
      rest of the entire cycle. In addition, thioredoxin reductase and glutathione
      reductase activities were measured, where the latter enzyme remained constant but
      thioredoxin reductase activities showed a biphasic behavior. The first peak
      coincided with the induction of 6BH4 de novo synthesis at the beginning of the
      hair cycle. The second peak was observed at mid-anagen, when melanogenesis takes
      place. Taken together, our results show the presence of autocrine pterin
      synthesis/recycling in human hair follicle cells under in vitro conditions, and a
      possible role for 6BH4 in the synchronized murine hair cycle.

PMID- 9764832
TI  - Anchorage-dependent expression of the vitamin D receptor in normal human
      keratinocytes.
AB  - Although the nuclear vitamin D receptor (VDR) is involved in the control of
      keratinocyte proliferation and differentiation by its ligand 1,25
      dihydroxyvitamin D3 [1,25(OH)2D3], its role in epidermal physiology remains
      poorly understood. Because VDR abundance reflects cellular responsiveness to
      1,25(OH)2D3, we investigated VDR expression in cultured human keratinocytes and
      identified cell anchorage and cytoskeletal integrity as essential requirements
      for the maintenance of VDR levels. Suspension culture rapidly suppressed VDR
      expression and 1,25(OH)2D3 responsiveness (as estimated by induction of 24
      hydroxylase mRNA), due to decreased transcription of the VDR gene. Concomitantly,
      overt growth arrest with p21WAF1 induction and cyclin D1 and c-myc suppression
      occurred, together with induction of differentiation markers and retinoid X
      receptor alpha, the heterodimeric partner for VDR. Reattachment of suspended
      keratinocytes to fibronectin led to a rapid restoration of VDR expression, which
      could be blocked by RGD peptides or a blocking anti-beta1 integrin antibody. VDR
      expression was also reduced by disruption of the actin cytoskeleton with
      cytochalasin D. Malignant keratinocytes (SCC12B2 and A431), characterized by,
      anchorage-independent growth, displayed a profound resistance to suspension
      induced suppression of VDR, cyclin D1, and c-myc. Taken together, our results
      associate VDR expression [and 1,25(OH)2D3 responsiveness] with cell adhesion and
      an organized cytoskeleton, which are also required for cell growth of primary
      cells.

PMID- 9764833
TI  - The cutaneous microfibrillar apparatus contains latent transforming growth factor
      beta binding protein-1 (LTBP-1) and is a repository for latent TGF-beta1.
AB  - The transforming growth factors-beta1 and beta2 (TGF-beta) stimulate synthesis of
      extracellular matrix proteins in vitro and appear upregulated in fibrotic
      conditions, in scar formation, and in wound healing. The extracellular matrix in
      turn might also act as a scavenger or repository for TGF-beta. We therefore
      studied the in situ distribution of latent TGF binding protein-1 (LTBP-1) and
      latent TGF-beta1 on extracellular matrix elements of normal human skin and skin
      regenerating from cultured keratinocyte autografts. We localized both LTBP-1 and
      latent TGF-beta1 to fibrillin-containing (elastic) microfibrils. Both LTBP-1 and
      latent TGF-beta1 were already present during the earliest stages of the de novo
      formation of the microfibrillar apparatus, i.e., on fusiform, randomly oriented
      microfibrils that later coalesced to form the typical candelabra-like structures
      in the papillary dermis. We show herewith that LTBP-1 exerts a dual role as a
      component of fibrillin-microfibrils of the skin and in targeting latent TGF-beta1
      to the cutaneous microfibrillar apparatus. Thus, this major connective tissue
      structure does not only serve as a force bearing element and scaffold for elastin
      deposition in the dermis, but also as an important repository for latent TGF-beta
      in the skin.

PMID- 9764834
TI  - Protein gene product 9.5 is expressed by fibroblasts in human cutaneous wounds.
AB  - In a study initially designed to evaluate reinnervation of human cutaneous wounds
      using an antibody to the neuroneal marker protein gene product (PGP) 9.5, we
      observed marked immunostaining of cells with morphologic features of fibroblasts
      in the wounds. PGP 9.5 has recently been shown to be an important enzyme in the
      highly conserved ubiquitin system of proteolysis. Because the ubiquitin system is
      known to play an important role in regulating the cell cycle, the presence of PGP
      9.5 in cells at a wound site was of considerable interest. Our objectives were to
      clarify the time frame for the appearance of PGP 9.5 and ubiquitin in wounds, to
      verify that PGP 9.5 is produced by wound fibroblasts, and to evaluate a potential
      role for these proteins in the tissue repair process. Standard incisional human
      wounds were stained with antibodies specific for PGP 9.5 and ubiquitin. At 7 d,
      stellate cells with morphologic features of fibroblasts stained for PGP 9.5,
      whereas earlier wounds were generally negative. In 14 and 21 d incised wounds and
      in chronic granulation tissue from nonhealing ulcers there was strong cellular
      staining for PGP 9.5 and for ubiquitin. These stellate cells also showed
      expression of mRNA for PGP 9.5 by reverse transcriptase-polymerase chain reaction
      in situ hybridization. PGP 9.5 was detected in cultured fibroblasts both by
      reverse transcriptase-polymerase chain reaction and by northern blot analysis.
      Confocal microscopy showed colocalization of antibodies to PGP 9.5 and prolyl-4
      hydroxylase (a fibroblast marker) as well as colocalization of PGP 9.5 and the
      platelet derived growth factor beta receptor. We conclude that ubiquitin and PGP
      9.5 were expressed by fibroblasts during the granulation tissue and remodeling
      phases wound healing. The mRNA for PGP 9.5 was demonstrated in stellate cells in
      chronic wounds and in fibroblasts in culture. The appearance of these degradative
      proteins in later wounds suggests a downregulation function in the wound healing
      response.

PMID- 9764835
TI  - Proteolytic cleavage and activation of pro-macrophage-stimulating protein and
      upregulation of its receptor in tissue injury.
AB  - Macrophage stimulating protein (MSP) exists in blood as inactive pro-MSP.
      Cleavage yields active MSP, the ligand for a membrane receptor (RON) that is
      expressed on keratinocytes as well as macrophages. Because both cells have roles
      in tissue injury, we looked for active MSP and expressed RON in wounds.
      Concentration of pro-MSP + MSP in wound exudates was in the range for optimal
      activity. Western blot showed that MSP comprised about half the total, in
      contrast to less than 10% of the total in blood plasma. The presence of MSP was
      attributed to an exudate pro-MSP convertase that had an inhibitor profile
      consistent with a trypsin-like serine protease. Exudate evoked morphologic
      changes in macrophages in vitro like that of MSP. Removal of this activity by an
      anti-MSP column shows that exudate stimulation of macrophages is due to MSP. RON
      was infrequently detected in normal skin. RON protein was markedly upregulated in
      burn wound epidermis and accessory structures, in proliferating cells or
      differentiated cells, or both. RON was also detected on macrophages and
      capillaries. Tissue injury leads to cleavage of pro-MSP to MSP, which has
      potential to act on keratinocytes, macrophages, and capillaries, all components
      of the wound healing response.

PMID- 9764837
TI  - Psoriatic plaques exhibit red autofluorescence that is due to protoporphyrin IX.
AB  - In evaluating the autofluorescence properties of normal and diseased skin we
      discovered that psoriatic plaques can emit a distinct red fluorescence when
      illuminated with UVA or blue light. Using a macrospectrofluorometer equipped with
      a 442 nm excitation laser, a sharp in vivo fluorescence emission peak around 635
      nm could be demonstrated within the plaques of 34 of 75 (45%) patients with
      psoriasis. This peak was absent from normal appearing skin of psoriatic patients
      and also from the skin of 66 patients with other dermatologic diseases. A
      microspectrofluorometer coupled with the same excitation laser was used to obtain
      emission spectra of separated epidermal sheets and dermis from plaques
      demonstrating macroscopic red autofluorescence. An emission peak around 635 nm
      was observed in all three patients thus studied, but only on spectra obtained
      from the epidermis. Additional spectra of vertical microscopic sections of intact
      psoriatic skin from five other patients revealed that the peak originated from
      the stratum corneum. Emission spectra from other microlocations including the mid
      epidermis and dermis of psoriatic and normal skin, as well as the stratum corneum
      of normal skin, failed to demonstrate a 635 nm peak. The excitation and emission
      fluorescence spectra of acid extracts of psoriatic scale from five patients were
      all similar to those of protoporphyrin IX in acid solution. High performance
      liquid chromatography identified the presence of protoporphyrin IX in the acid
      extracts from psoriatic scale of the same patients. We conclude that native
      psoriatic plaques can exhibit red autofluorescence that is due to elevated levels
      of protoporphyrin IX within scales.

PMID- 9764836
TI  - Novel function of metallothionein in photoprotection: metallothionein-null mouse
      exhibits reduced tolerance against ultraviolet B injury in the skin.
AB  - We have shown previously that injection of cadmium chloride (Cd2+) depletes the
      number of ultraviolet B (UVB)-induced sunburn cells in the mouse skin in vivo,
      and that Cd2+ treatment enhances UVB resistance in cultured keratinocytes in
      vitro, indicating the photoprotective role of Cd2+-induced metallothioneins (MT)
      with antioxidant property against UVB injury; however, there has been no direct
      evidence for the role of MT in UV protection. To improve our understanding of MT
      in photoprotection, MT-null mouse deficient in its MT-1 and MT-2 genes was
      studied. Skin explants were preliminarily exposed to medium alone, Cd2+ and Cd2+
      plus buthionine S,R-sulfoximine, an inhibitor of glutathione synthesis. We then
      compared the number of UVB-induced sunburn cells and apoptotic cells in the
      epidermis of MT-null mice with that of control mice using organ culture systems.
      The skin of MT-null mice developed a greater number of sunburn cells and
      apoptotic cells than did that of normal mice in all experimental conditions.
      These findings indicate that the skin of MT-null mouse is readily injured by UVB
      irradiation. MT-null mouse provided direct evidence of the photoprotective effect
      of cellular MT in the skin.

PMID- 9764838
TI  - Altered expression of epithelial cell surface glycoconjugates and intermediate
      filaments at the margins of mucosal wounds.
AB  - Alterations in cell to cell adhesion are necessary to enable the type of cell
      movements that are associated with epithelial wound healing and malignant
      invasion. Several studies of transformed cells have related epithelial cell
      movement to changes in the cell surface expression of the carbohydrate structures
      represented by the ABO blood group antigens and, in particular, by Lewis antigens
      and their biosynthetic precursors. To study further the relationship between cell
      surface carbohydrates and keratinocyte cell movement, experimental wounds were
      created in human oral mucosa and examined by immunohistochemical methods for
      their expression of selected cytokeratins (K5, K16, K19), basement membrane
      components (laminin alpha5 and gamma2-chains, BP180, collagen IV and collagen
      VII), and blood group antigen precursor structures Le(x), sialosyl-Le(x), Le(y),
      H antigen, N-acetyllactosamine, and sialosyl-T antigen. The changes induced by
      wounding in the expression of collagen IV, laminin gamma2-chain (laminin-5), and
      laminin alpha5-chain were similar to those found in skin wounds and served to
      define the region of epithelial movement. This region was found to show a marked
      increase in staining for both Lewis antigen Y (Le(y)) and H blood group antigen,
      and decreased staining of Le(x), thus indicating an upregulation in wounded
      epithelium of the fucosyltransferases responsible for the synthesis of the H
      antigen. The changes in carbohydrate expression extended beyond the wound margin
      into the nonwounded epithelium, a pattern of expression similar to K16, which was
      also strongly upregulated in both the outgrowth and the adjacent nonwounded
      epithelium. These findings provide further support for an influence of such
      carbohydrate structures on the migratory behavior of epithelial cells.

PMID- 9764839
TI  - Reduction of intrafollicular apoptosis in chemotherapy-induced alopecia by
      topical calcitriol-analogs.
AB  - Chemotherapy-induced alopecia is thought to result from cytotoxic and apoptosis
      related damage to the hair follicle. This study was designed to confirm whether
      keratinocyte apoptosis is indeed induced in growing (= anagen) hair follicles of
      C57 BL/6 mice after the injection of cyclophosphamide, using improved methods for
      histologic detection of apoptotic cells in murine skin. More importantly, we
      asked whether topical calcitriol-analogs are able to modulate cyclophosphamide
      induced apoptosis in vivo, because there are conflicting reports on the effects
      of calcitriols on apoptosis in vitro. Anagen was induced in telogen mice on day 0
      by depilation. Starting on day 5 post-depilation, the back skin of mice was
      topically treated with either 0.2 microg 1,25-dihydroxyvitamin D3, 2.0 microg
      calcipotriol, 0.02 microg KH 1060, or vehicle (ethanol) only. On the last day of
      treatment (i.e., day 9 post-depilation), all mice received 150 mg
      cyclophosphamide i.p. per kg as a single dose to induce alopecia, or vehicle
      (aqua dist.). Analysis of the treated skin by in situ-end labeling (using a
      modified terminal UTP nucleotide end labeling technique suitable for murine
      skin), by Hoechst 33342 stain, and by DNA electrophoresis on days 10 and 14,
      revealed the induction of massive apoptosis in cyclophosphamide-treated anagen
      hair bulbs, which was most prominent on day 10, whereas controls showed no
      follicular apoptosis. The calcitriol-pretreated groups demonstrated a significant
      reduction of apoptosis, with a maximal inhibition seen on day 14. This confirms
      that cyclophosphamide indeed induces massive keratinocyte apoptosis in anagen
      hair follicles, and provides evidence that topical calcitriol-analogs can
      suppress epithelial cell apoptosis in vivo. The mouse model employed here offers
      an excellent tool for dissecting the as yet poorly understood controls of
      keratinocyte apoptosis in situ and its pharmacologic manipulation.

PMID- 9764840
TI  - Efficient expression of naked plasmid DNA in mucosal epithelium: prospective for
      the treatment of skin lesions.
AB  - Mucocutaneous gene therapy offers exciting new treatment modalities for skin
      lesions. Transient expression of naked plasmid DNA could be used as a local
      treatment of various skin lesions where the corresponding gene product (protein)
      has therapeutic or immunization potential. We analyzed the time course,
      magnitude, and histologic expression of the indicator plasmid DNA (pCMV:beta-Gal)
      in mucosal epithelium and papilloma lesions. Upon direct injection of naked
      plasmid DNA (20 microg) into oral mucosa, expression occurred at high local
      concentrations, up to 35-fold higher than in comparable injections into the
      epidermis. Due to the accelerated turnover of mucosal epithelium beta
      galactosidase positive epithelial cells were detected in the basal and suprabasal
      layers as early as 3 h after injection, whereas only the most superficial mucosal
      layers demonstrated beta-galactosidase staining at 24 h post-injection. These
      biologic characteristics need to be taken into consideration when clinical
      applications of expressing naked plasmid DNA in epithelial tissues are
      considered.

PMID- 9764841
TI  - Differential regulation of epidermal cell tumor-antigen presentation by IL-1alpha
      and IL-1beta.
AB  - IL-1 exists in two forms, termed IL-1alpha and IL-1beta, which exert similar
      effects in a number of biologic models. Recently, there have been reports of some
      differences in the activities of these two species in some systems. To address
      this issue with regard to Langerhans cells, Langerhans cell-enriched preparations
      of epidermal cells were treated with either IL-1alpha or IL-1beta before pulsing
      with S1509a tumor-associated antigens and subsequent use for immunization of
      naive mice to S1509a. While epidermal cells treated with 100 U IL-1beta per ml
      were able to induce protective tumor immunity (as indicated by the rejection of a
      subsequent tumor challenge with viable S1509a tumor cells), epidermal cells
      treated with 100 U IL-1alpha per ml failed to confer protective immunity. At 1000
      U per ml, IL-1beta also inhibited the ability of epidermal cells to induce tumor
      immunity. To investigate the effects of the two IL-1 forms on elicitation of
      tumor immunity, naive mice were immunized against the S1509a tumor by s.c.
      injection of dead S1509a cells. Epidermal cells enriched for Langerhans cells
      were treated with either 100 U IL-1alpha or IL-1beta per ml before tumor
      associated antigens-pulsing. Epidermal cells were then washed and injected into a
      hind footpad of tumor immune mice and 24 h footpad swelling was assessed as a
      measure of delayed-type hypersensitivity. Exposure to IL-1alpha led to suppressed
      elicitation of delayed-type hypersensitivity, whereas IL-1beta treated epidermal
      cells elicited a normal (100 U per ml) or enhanced (1000 U per ml) level of
      delayed-type hypersensitivity. Previous experiments indicated that the
      suppressive effects of IL-1alpha on induction of immunity may be mediated by TNF
      alpha. Therefore, the ability of IL-1alpha or IL-1beta to induce epidermal cell
      production of TNF alpha was assessed. IL-1alpha induced epidermal cells to
      secrete significantly higher amounts of TNF alpha protein compared with
      stimulation with IL-1beta. IL-1alpha and IL-1beta appear to differentially
      regulate epidermal cell antigen presenting capability.

PMID- 9764842
TI  - Endogenous EGF-family growth factors are necessary for the progression from the
      G1 to S phase in human keratinocytes.
AB  - Recently several endogenous epidermal growth factor (EGF)-family growth factors
      (transforming growth factor-alpha, amphiregulin, and heparin-binding EGF-like
      growth factor) have been identified in human keratinocytes. These factors are
      known to play an important role in the regulation of cell proliferation. Here we
      show that the interaction between these factors and EGF receptor are key factors
      in the progression from the G1 phase to the S phase (the G1/S progression) in
      human keratinocytes. In this study, human keratinocytes were cultured in serum
      free MCDB153 medium and then partially synchronized by isoleucine deprivation.
      After synchronization, the number of S phase cells increased and reached a
      maximum after 18-24 h. The immediate addition of anti-EGF receptor blocking
      antibody (1 microg per ml) to synchronized cells decreased S phase cells by 42.5%
      compared with untreated keratinocytes at 18 h. By contrast, the addition of anti
      EGF receptor antibodies at 12 h or later did not alter the percentage of S phase
      cells. Northern blot analysis of synchronized cells demonstrated that mRNA
      expression of transforming growth factor-alpha, amphiregulin, heparin-binding EGF
      like growth factor, and EGF receptor reached a maximum within 0.5-3 h after
      synchronization, when many cells initiated progression from the G1 to the S
      phase. The results show that anti-EGF receptor antibodies block the G1/S
      progression and the rapid increase of mRNA expression of endogenous EGF-family
      growth factors and EGF receptor during G1/S progression. These findings indicate
      that growth factor binding and EGF receptor activation are involved in the G1/S
      cell cycle progression of human keratinocytes.

PMID- 9764843
TI  - Patients with allergic contact dermatitis to nickel and nonallergic individuals
      display different nickel-specific T cell responses. Evidence for the presence of
      effector CD8+ and regulatory CD4+ T cells.
AB  - To investigate the mechanisms underlying the expression of allergic contact
      dermatitis, we compared the characteristics of nickel (Ni)-specific T cell
      responses in 10 patients with allergic contact dermatitis to Ni and in 10
      healthy, nonallergic individuals. CD4+ T cells purified from peripheral blood of
      both allergic and nonallergic subjects proliferated similarly to NiSO4 in vitro,
      with the responses mostly restricted to CD4+ CD45RO+ memory T cells. In contrast,
      Ni-specific CD8+ T cell responses were detected only in allergic patients.
      Limiting dilution assay confirmed a high frequency of Ni-specific CD4+ T cells in
      both individual categories, and of Ni-specific CD8+ T cells in allergic patients,
      but not in nonallergic persons. Ni-specific CD4+ T cell clones prepared from
      nonallergic subjects displayed lower interferon-gamma and higher interleukin-10
      production compared with T cell clones from allergic patients. The T cell skin
      homing receptor, cutaneous lymphocyte-associated antigen, was expressed on the
      large majority of specific CD4+ clones from both the groups. Finally, Ni-specific
      CD8+ clones prepared from patients also expressed the cutaneous lymphocyte
      associated antigen receptor, and released high interferon-gamma and no
      interleukin-4. In aggregate, the results suggest that the presence of specific
      CD8+ T cells and a distinct pattern of cytokine release (e.g., an augmented
      production of interleukin-10) by CD4+ T cells can be important elements in
      determining whether a hapten induces allergy or a silent immune response.

PMID- 9764844
TI  - Non-coherent near infrared radiation protects normal human dermal fibroblasts
      from solar ultraviolet toxicity.
AB  - The sun is the most important and universal source of non-ionizing radiation shed
      on human populations. Life evolved on Earth bathed by this radiation. Solar UV
      damages cells, leading to deleterious conditions such as photoaging and
      carcinogenesis in human skin. During the process of evolution, the cells selected
      dark- and light-dependent repair mechanisms as a defence against these hazardous
      effects. This study describes the induction by non-coherent infrared radiation
      (700-2000 nm), in the absence of rising temperature, of a strong cellular defense
      against solar UV cytotoxicity as well as induction of cell mitosis. Blocking
      mitoses with arabinoside-cytosine or protein synthesis with cycloheximide did not
      abolish the protection, leading to the conclusion that this protection is
      independent of cell division and of protein neosynthesis. The protection provided
      by infrared radiation against solar UV radiation is shown to be a long-lasting
      (at least 24 h) and cumulatif phenomenon. Infrared radiation does not protect the
      lipids in cellular membranes against UVA induced peroxidation. The protection is
      not mediated by heat shock proteins. Living organisms on the Earth's surface are
      bathed by infrared radiation every day, before being submitted to solar UV. Thus,
      we propose that this as yet undescribed natural process of cell protection
      against solar UV, acquired and preserved through evolutional selection, plays an
      important role in life maintenance. Understanding and controlling this mechanism
      could provide important keys to the prevention of solar UV damage of human skin.

PMID- 9764845
TI  - Cholecalciferol induces prostaglandin E2 biosynthesis and transglutaminase
      activity in human keratinocytes.
AB  - In this study, we examined the effects of cholecalciferol, a primary keratinocyte
      metabolite and precursor of the hydroxylated form of vitamin D3, 1alpha,25
      dihydroxyvitamin D3 [1alpha,25(OH)2D3], on prostaglandin E2 (PGE2) production in
      human keratinocytes by examining its respective effects on cyclooxygenase-1 (COX
      1), cyclooxygenase-2 (COX-2), and cytosolic phospholipase A2 (cPLA2) expression,
      the rate-limiting enzymes regulating PGE2 biosynthesis and differentiation of
      keratinocytes. Cholecalciferol induced PGE2 production, whereas 1alpha,25(OH)2D3
      had no effect on PGE2 production both in normal human epidermal keratinocytes and
      in the immortalized human keratinocyte cell line, HaCaT. In HaCaT cells, neither
      COX-1 mRNA nor protein was detectable without stimulation and COX-1 expression
      did not increase in response to cholecalciferol treatment. Although cPLA2 mRNA
      and protein were constitutively expressed in untreated HaCaT cells, expression
      levels did not increase in response to cholecalciferol treatment; however, unlike
      COX-1 and cPLA2 expression, COX-2 mRNA and COX-2 protein expression increased in
      response to cholecalciferol treatment. Calphostin C, a potent protein kinase C
      inhibitor, significantly reduced cholecalciferol-induced PGE2 production by
      inhibiting cholecalciferol-enhanced COX-2 mRNA and protein expression. These
      results indicate that (i) 1alpha,25(OH)2D3 does not induce PGE2 biosynthesis in
      keratinocytes, (ii) cholecalciferol-induced PGE2 production is primarily COX-2
      dependent, and (iii) cholecalciferol enhances both COX-2 mRNA and protein
      expression, via a protein kinase C-dependent mechanism in human keratinocytes.
      Furthermore, cholecalciferol increased total cellular transglutaminase activity
      dose dependently, suggesting a potential role for cholecalciferol in regulating
      the differentiation of human keratinocytes.

PMID- 9764846
TI  - The herbal medicine Sho-saiko-to inhibits growth and metastasis of malignant
      melanoma primarily developed in ret-transgenic mice.
AB  - Sho-saiko-to is the most popular herbal medicine in Japan. We investigated the
      anti-tumor and anti-metastatic effects of Sho-saiko-to and its chemically defined
      ingredients on the primary skin melanoma that developed in a metallothionein-I
      (MT)/ret transgenic mouse line and on a melanoma cell line (Mel-ret), which was
      derived from a primary tumor developed in a MT/ret transgenic mouse. In vitro,
      Sho-saiko-to suppressed the growth of Mel-ret cells more strongly than any single
      ingredient of Sho-saiko-to, although baicalin as one of several ingredients
      tested also suppressed it significantly. In vivo, Sho-saiko-to (i) significantly
      (p < 0.02) prolonged the onset of tumor development (1.5 mo), (ii) definitely
      retarded the transition to malignancy, (iii) significantly decreased the
      incidence of distant metastasis to brain (p < 0.002), kidney (p < 0.05), and
      liver (p < 0.05) at the malignant stage, and (iv) significantly (p < 0.02)
      prolonged life span (2.6 mo). Moreover, Sho-saiko-to and baicalin down-regulated
      the matrix metalloproteinase-2 and -9 expression levels, and upregulated their
      inhibitor expression level in both the primary tumors and Mel-ret cells. In
      conclusion, Sho-saiko-to displayed anti-tumor and anti-metastatic effects on
      melanoma with regulation of the balance of matrix metalloproteinase and tissue
      inhibitor of the matrix metalloproteinase levels.

PMID- 9764848
TI  - Integrins of the beta1 family influence keratinocyte-lymphocyte interaction.
AB  - Data from the literature indicate that ICAM-1 molecules play an important role in
      keratinocyte interactions with lymphocytes via the lymphocyte function-associated
      1 lymphocyte-adhesion molecule. We examined the role of beta1 integrins in
      keratinocyte-lymphocyte adhesion under different activation conditions. Among the
      beta1 integrins expressed on keratinocytes and lymphocytes detected by indirect
      immunofluorescence microscopy and flow cytofluorometry, primarily the alpha2 and
      the alpha3 subunits on both cell types were involved in keratinocyte-lymphocyte
      adhesion. Moreover, the highest adhesion level was observed when both cell types
      were activated by IFN-gamma for keratinocytes and phorbol 12-myristate 13-acetate
      for lymphocytes, suggesting that the former involved the protein kinase C
      pathway. Keratinocyte activation, characterized by the expression of ICAM-1, a
      decrease of beta1 integrins, and the absence of alpha5beta1 integrin, was
      required for optimal lymphocyte adhesion. Thus, beta1 integrins remaining at the
      surface of IFN-gamma-treated keratinocytes could be activated by this cytokine,
      and could synergize with ICAM-1 and lymphocyte function-associated-1 molecules to
      consolidate keratinocyte-lymphocyte adhesion.

PMID- 9764847
TI  - Interleukin-17 and interferon-gamma synergize in the enhancement of
      proinflammatory cytokine production by human keratinocytes.
AB  - Keratinocytes are influenced by cytokines released by skin-infiltrating T
      lymphocytes. IL-17 is produced by activated CD4+ T cells and can stimulate
      epithelial cells. We investigated whether IL-17 could modulate the cytokine
      production and cell-surface molecule expression of keratinocytes. The effects of
      IL-17 were compared with those of IFN-gamma, which is also derived from activated
      T cells and is a strong stimulator for keratinocytes. IL-17 enhanced the mRNA and
      protein production of the proinflammatory cytokines IL-6 and IL-8 in a
      concentration-dependent way, and induced a weak expression of intercellular
      adhesion molecule (ICAM)-1 and HLA-DR. The production of IL-1alpha and IL-15 was
      not altered. IFN-gamma augmented the production of IL-6, IL-8, and IL-15 and
      strongly induced both cell-surface molecules. IL-17 and IFN-gamma showed marked
      synergism in the stimulation of IL-6 and IL-8 protein secretion and, to a lesser
      extent, in the induction of ICAM-1 and HLA-DR expression. The majority of the
      CD4+ and CD8+ T cell clones derived from lesional psoriatic skin expressed IL-17
      mRNA, suggesting that skin-infiltrating T cells can produce this cytokine. This
      IL-17 mRNA expression was detectable in T helper cell type 1 and type 2 and did
      not correlate with the IFN-gamma or IL-4 production. In addition, IL-17 mRNA is
      detectable in biopsies from lesional psoriatic skin, but not in nonlesional
      control biopsies. Our study indicates that IL-17 is a proinflammatory cytokine,
      which could amplify the development of cutaneous inflammation and may support the
      maintenance of chronic dermatoses, through stimulation of keratinocytes to
      augment their secretion of proinflammatory cytokines.

PMID- 9764849
TI  - Curcumin induces a p53-dependent apoptosis in human basal cell carcinoma cells.
AB  - Curcumin, a potent antioxidant and chemopreventive agent, has recently been found
      to be capable of inducing apoptosis in human hepatoma and leukemia cells by way
      of an elusive mechanism. Here, we demonstrate that curcumin also induces
      apoptosis in human basal cell carcinoma cells in a dose- and time-dependent
      manner, as evidenced by internucleosomal DNA fragmentation and morphologic
      change. In our study, consistent with the occurrence of DNA fragmentation,
      nuclear p53 protein initially increased at 12 h and peaked at 48 h after curcumin
      treatment. Prior treatment of cells with cycloheximide or actinomycin D abolished
      the p53 increase and apoptosis induced by curcumin, suggesting that either de
      novo p53 protein synthesis or some proteins synthesis for stabilization of p53 is
      required for apoptosis. In electrophoretic mobility gel-shift assays, nuclear
      extracts of cells treated with curcumin displayed distinct patterns of binding
      between p53 and its consensus binding site. Supportive of these findings, p53
      downstream targets, including p21(CIP1/WAF1) and Gadd45, could be induced to
      localize on the nucleus by curcumin with similar p53 kinetics. Moreover, we
      immunoprecipitated extracts from basal cell carcinoma cells with different anti
      p53 antibodies, which are known to be specific for wild-type or mutant p53
      protein. The results reveal that basal cell carcinoma cells contain exclusively
      wild-type p53; however, curcumin treatment did not interfere with cell cycling.
      Similarly, the apoptosis suppressor Bcl-2 and promoter Bax were not changed with
      the curcumin treatment. Finally, treatment of cells with p53 antisense
      oligonucleotide could effectively prevent curcumin-induced intracellular p53
      protein increase and apoptosis, but sense p53 oligonucleotide could not. Thus,
      our data suggest that the p53-associated signaling pathway is critically involved
      in curcumin-mediated apoptotic cell death. This evidence also suggests that
      curcumin may be a potent agent for skin cancer prevention or therapy.

PMID- 9764850
TI  - Antibody responses to melanoma/melanocyte autoantigens in melanoma patients.
AB  - Melanogenesis-related proteins play important roles in melanin synthesis and
      antigenicity of melanomas. Identification of highly expressed melanoma-associated
      antigens (MAA) that are immunogenic in humans will provide potential targets for
      cancer vaccines. Melanogenesis-related proteins have been shown to be MAA.
      Autoantibody responses to these MAA have been shown to react with melanoma cells
      and melanocytes, and suggested to play a role in controlling melanoma
      progression. To assess antibody responses to potential melanoma/melanocyte
      autoantigens, the open-reading frame sequences of tyrosinase, tyrosinase-related
      protein (TRP)-1, TRP-2, and melanoma-associated glycoprotein antigen family
      (gp100/pmel17) genes were cloned and expressed as recombinant proteins in E.
      coli. Purified recombinant antigens were employed to detect antibodies in sera of
      melanoma patients and normal healthy donors. By affinity enzyme-linked
      immunosorbent assay and western blotting, all recombinant antigens were shown to
      be antigenic. The main subclass of antibody response to these antigens was IgG.
      Most importantly this study demonstrated anti-TRP-2 and anti-gp100/pmel17 IgG
      responses in melanoma patients. Only one of 23 normal donors had an antibody
      response to the antigens tested. MAA-specific IgG antibodies in sera were
      assessed in melanoma patients (n = 23) pre- and post-polyvalent melanoma cell
      vaccine treatment. Polyvalent melanoma cell vaccine treatment enhanced anti-MAA
      antibody responses; however, only anti-TRP-2 and anti-gp100/pmel17 antibody
      response was enhanced. These studies suggest that four melanogenesis-related
      proteins are autoimmunogenic and can be used as potential targets for active
      specific immunotherapy.

PMID- 9764851
TI  - Human Langerhans cells express a novel form of the leukocyte common antigen
      (CD45).
AB  - CD45 is a family of transmembrane glycoproteins that function as protein tyrosine
      phosphatases. All isoforms exhibit common CD45 epitopes, whereas the restricted
      CD45 epitopes (RA, RB, and RO) are each limited to one or more isoforms. In prior
      studies, we showed that human Langerhans cells in normal epidermis express a
      novel CD45 phenotype. They express common CD45 epitopes but are
      characteristically RA- RB- RO-. This suggests that Langerhans cells can express a
      novel form of CD45. In order to clarify this issue further, mRNA extracted from
      enriched Langerhans cell preparations was reverse transcribed into cDNA. The 5'
      portion of CD45 cDNA was then amplified using polymerase chain reaction primers
      complementary to exon 2 and exons 9-10, which flank the CD45 variable exon region
      (exons 4-6). Cloning and sequencing of the dominant 441 bp polymerase chain
      reaction product revealed the following exon configuration for the 5' translated
      region of Langerhans cells CD45: exon 3/7/8/9/10. This is the same exon
      configuration associated with the 180 kd CD45 isoform expressed by memory T cells
      and monocytes/macrophages; however, these cell types are RO+ whereas normal
      Langerhans cells are RO-. The RO epitope is known to be an oligosaccharide with a
      terminal sialic acid moiety. Therefore, we determined the expression of a related
      epitope, OPD4, by Langerhans cells. This is another terminal sialic acid moiety
      expressed by the 180 kd CD45 isoform of memory T cells but not by
      monocytes/macrophages. Langerhans cells were OPD4-. Our data suggest that memory
      T cells, monocytes/macrophages, and Langerhans cells all express a common CD45
      transcript lacking exons 4-6; however, this transcript appears to undergo lineage
      specific, post-translational glycosylation to create three distinct CD45
      glycoproteins: RO+ OPD4+, RO+ OPD4-, and RO- OPD4-, which are expressed typically
      by memory T cells, monocytes/macrophages, and Langerhans cells, respectively.
      Because these epitopes are located extracellularly, they are postulated to allow
      differential responses to extracellular stimuli by creating differential ligand
      specificity.

PMID- 9764852
TI  - The pH gradient over the stratum corneum differs in X-linked recessive and
      autosomal dominant ichthyosis: a clue to the molecular origin of the "acid skin
      mantle"?
AB  - In a search for pathogenetic mechanisms underlying retention hyperkeratosis, we
      examined the pH gradient over the stratum corneum in 13 male patients suffering
      from either x-linked recessive (XRI) or autosomal dominant ichthyosis vulgaris.
      For recording pH values, a flat glass electrode was repeatedly applied to the
      skin during tape stripping of mildly involved forearm skin. Before stripping,
      surface pH was higher in ichthyosis vulgaris (5.3 +/- 0.7; n = 7) than in XRI
      (4.6 +/- 0.4; n = 6; p < 0.05) and healthy control men (4.5 +/- 0.2; n = 7; p <
      0.01). Removal of stratum corneum, which required 100-240 strippings in
      ichthyotic skin and 80-120 strippings in healthy control skin, disclosed markedly
      different pH variations in the two types of ichthyosis. The major abnormality in
      ichthyosis vulgaris skin was that a neutral pH was attained already halfway
      through the horny layer, possibly reflecting a congenital lack of acidic
      breakdown products from keratohyaline. By contrast, stripping of XRI skin
      revealed a shallow pH gradient that plateaued at 6.2-6.6, instead of about 7 as
      in normal and ichthyosis vulgaris skin. A likely explanation is the XRI
      associated accumulation of cholesterol sulfate in lower stratum corneum. Our
      results suggest that the "acid mantle" of normal skin, which penetrates deep into
      the stratum corneum, is the combined result of cornification-associated organic
      acids and back-diffusion of acid material from the surface. Because corneocyte
      desquamation involves many pH-dependent enzymes, abnormalities in the
      transcorneal pH gradient might play a role in the pathogenesis of ichthyosis.

PMID- 9764853
TI  - (Pheo)melanin photosensitizes UVA-induced DNA damage in cultured human
      melanocytes.
AB  - The question of whether melanins are photoprotecting and/or photosensitizing in
      human skin cells continues to be debated. To evaluate the role of melanin upon
      UVA irradiation, DNA single-strand breaks (ssb) were measured in human
      melanocytes differing only in the amount of pigment produced by culturing at two
      different concentrations, basic (0.01 mM) or high (0.2 mM), of L-tyrosine, the
      main precursor of melanin. In parallel, pheo- and total melanin contents of the
      cells were determined. Identical experiments were performed with two melanocyte
      cultures derived from a skin type I and a skin type VI individual. For the first
      time the correlation between UVA-induced genotoxicity and pheo-/total melanin
      content has been investigated. We observed that cultured in basic medium, the
      skin type VI melanocytes contained 10 times more total melanin and about seven
      times more pheomelanin than the skin type I melanocytes. Elevation of tyrosine
      level in the culture medium resulted in an increase of both pheo- and total
      melanin levels in both melanocyte cultures; however, the melanin composition of
      skin type I melanocytes became more pheomelanogenic, whereas that of skin type VI
      melanocytes remained the same. The skin type VI melanocytes cultured in basic
      medium demonstrated a very high sensitivity (1.18 ssb per 10(10) Da per kJ per
      m2) toward UVA that is probably related to their high pheo- and total melanin
      content. Their UVA sensitivity, however, did not change after increasing their
      melanin content by culturing at high tyrosine concentration. In contrast, the
      skin type I melanocytes demonstrated a low sensitivity (0.04 ssb per 10(10) Da
      per kJ per m2) toward UVA when cultured in basic medium, but increasing their
      melanin content resulted in a 3-fold increase in their UVA sensitivity (0.13 ssb
      per 10(10) Da per kJ per m2). These results demonstrate that UVA-irradiated
      cultured human melanocytes are photosensitized by their own synthesized
      chromophores, most likely pheomelanin and/or melanin intermediates.

PMID- 9764854
TI  - Effects of UVB on the synthesis of complement proteins by keratinocytes.
AB  - UVB exposure of the skin results in increased production of several cytokines by
      keratinocytes and infiltration of inflammatory cells. We hypothesized that UVB
      may increase the expression of complement (C) components and C-regulatory
      proteins by keratinocytes. In vivo, UVB may upregulate these proteins by direct
      effects or via cytokines released by keratinocytes or infiltrating inflammatory
      cells. In vitro, UVB may upregulate these proteins only directly, because of
      dilution of released cytokines in the medium. To test this, we exposed cultured
      human keratinocytes to UVB (0-64 J per m2) and monitored C3 and Factor B release
      in the medium by enzyme-linked immunosorbent assay, and surface expression of
      decay accelerating factor, membrane cofactor protein, and CD59 by flow cytometry.
      Keratinocytes produced small amounts of C3 and Factor B, which remained
      unaffected by UVB. UVB (32 J per m2) caused a transient upregulation of all three
      C-regulatory proteins. Decay accelerating factor expression was maximal at 48 h
      (1.81 +/- 0.06-fold increase in mean fluorescence intensity over nonexposed
      cells), membrane cofactor protein at 72 h (2.13 +/- 0.09-fold increase in mean
      fluorescence intensity), and CD59 at 120 h (1.96 +/- 0.09-fold increase in mean
      fluorescence intensity), returning to baseline values within 96, 192, and 192 h,
      respectively. Exposure to 64 J per m2 resulted in significant cell death; cells
      surviving this dose up to 48 h expressed a higher level of all the three proteins
      than those surviving 32 J per m2. In conclusion, UVB upregulated membrane
      cofactor protein, decay accelerating factor, and CD59 on keratinocytes without
      affecting the constitutive release of C3 and Factor B. Thus, UVB can increase the
      resistance of keratinocytes against their own C known to be produced excessively
      in response to cytokines of inflammatory cells that infiltrate the skin following
      UVB exposure.

PMID- 9764855
TI  - Phenotypic characterization of human skin mast cells by combined staining with
      toluidine blue and CD antibodies.
AB  - Mast cells (MC) are important cellular components of the immune network in
      diverse organs. The skin MC has likewise been implicated in IgE- and complement
      mediated cutaneous reactions. Such reactions supposedly involve specific cell
      surface membrane receptors. In this study, the cell surface marker profile of
      human skin MC was established using monoclonal antibodies (MoAb) against defined
      CD antigens. MC were isolated from juvenile foreskin (n = 55) and adult mammary
      skin (n = 5). The reactivity of MC with MoAb was assessed by a combined toluidine
      blue/immunofluorescence staining technique. Confirming our previous analyses on
      lung MC, foreskin MC reacted with MoAb against CD9, CD29, CD33, CD43, CD44, CD45,
      CD46, CD51, CD54, CD55, CD58, CD59, CD61, and CD117 (c-kit). Foreskin MC were
      also recognized by MoAb to CD47, CD48, CD49d, CD53, CD60, CD63, CD81, CD82, CD84,
      CD87, CD92, CD97, CD98, and CD99. Recently clustered CD antigens detectable on
      foreskin MC were CD147 (neurothelin), CD149 (MEM133), CD151 (PETA-3), and CD157
      (BST-1). In contrast to lung MC and MC from adult skin, foreskin MC were found to
      express CD88 (C5aR). Also, cutaneous MC (from both juvenile foreskin and adult
      mammary skin), but not lung MC, were found to bind the CD32 MoAb IV.3, 2E1, and
      FLI8.26 (Fc gammaRII). The CD50 antigen (ICAM-3) was detectable on lung MC, but
      not on foreskin MC or MC of adult mammary skin. In summary, our data show that
      cutaneous MC and lung MC express an almost identical phenotype; however, in
      contrast to lung MC, cutaneous MC appear to express substantial amounts of CD32
      and to lack CD50. In addition, foreskin MC, unlike MC from adult skin or lung,
      express CD88.

PMID- 9764856
TI  - Prevalence of antibodies against virus-like particles of Epidermodysplasia
      verruciformis-associated HPV8 in patients at risk of skin cancer.
AB  - There is increasing evidence for widespread occurrences of infection with
      Epidermodysplasia verruciformis-related human papillomaviruses, both in the
      general population and in immunosuppressed patients. In order to test for the
      prevalence of antibodies directed against the native L1 epitopes exposed on the
      surface of the virions, we have established an IgG-specific enzyme-linked
      immunosorbent assay with L1 virus-like particles of the Epidermodysplasia
      verruciformis-specific human papillomavirus 8 as antigen to screen 567
      representative serum samples from the general population and
      immunosuppressed/dermatologic patients. Among healthy European donors (n = 210),
      7.6% were found to be seropositive. In a group of renal transplant recipients (n
      = 185) the antibody prevalence was elevated to 21.1%, irrespective of the
      presence or absence of skin cancer. High positivity rates could be detected among
      (i) immunocompetent patients with nonmelanoma skin tumors (45.6%, n = 79) and
      (ii) Psoralene/UVA treated psoriasis patients (42.9%, n = 42). In contrast, anti
      human papillomavirus 8-virus-like particle antibodies were found in only 6.8% of
      Hodgkin lymphoma patients (n = 44).

PMID- 9764857
TI  - A novel insertional mutation in loricrin in Vohwinkel's Keratoderma.
AB  - A mutation in the gene encoding loricrin has recently been reported in a subset
      of patients with Vohwinkel's Keratoderma manifesting an associated ichthyosiform
      dermatosis. We have studied a further kindred with this clinical phenotype.
      Microsatellite marker analysis was consistent with linkage to chromosome 1q21 and
      direct sequencing of loricrin identified a heterozygous mutation with an
      insertion of a T residue at codon 209. This mutation is predicted to produce a
      mutant protein with a frameshift of its terminal 107 amino acids and to be 22
      amino acids longer than the wild-type protein due to a delayed termination codon.
      The only previously reported mutation is a G insertion producing a frameshift
      after codon 231. The novel mutation we report is likely to have a similar
      functional effect on cornified envelope formation, with disturbance of
      transglutaminase-mediated cross-linking of envelope components, and serves to
      confirm the predicted role of insertional mutations in Vohwinkel's Keratoderma
      associated with ichthyosis.

PMID- 9764858
TI  - Urocanic acid binds to GABA but not to histamine (H1, H2, or H3) receptors.

PMID- 9764859
TI  - UV immunosuppression and skin cancer.

PMID- 9764860
TI  - Problems related to circadian rhythms in human skin and their validation.

PMID- 9764861
TI  - Mitochondrial DNA deletions in human skin reflect photo- rather than chronologic
      aging.

PMID- 9764862
TI  - Gynecologic effects of tamoxifen and the association with endometrial carcinoma.
AB  - Tamoxifen has been used as an adjuvant therapy for breast cancer for nearly two
      decades. The benefits of adjuvant tamoxifen therapy in prolonging disease-free
      and overall survival have been shown in randomized clinical trials. Despite this,
      some developing evidence suggests that tamoxifen causes a 2- to 3-fold increase
      in endometrial cancer. This paper reviews the reports of endometrial carcinoma in
      tamoxifen-treated patients. Two hundred fifty cases of endometrial carcinoma are
      reported, but only one case is identified in a premenopausal woman. When
      documented, 77% (n=127) of the cases are good-grade (grade 1 or 2) and 80%
      (n=125) are stage-I disease. Since the distribution of good grade (79%) and stage
      I (74%) from the Surveillance, Epidemiology and End Results (SEER) data are
      comparable, concerns about more aggressive or late-stage disease appear to be
      unwarranted. The modest increase in the incidence of early-stage, good-grade
      endometrial carcinoma described during tamoxifen therapy suggests that it would
      be unreasonable to institute an aggressive detection strategy of endometrial
      biopsies. This approach would only lead to further detection bias and would not
      be cost-effective. Physicians should ensure that patients do not have pre
      existing endometrial cancer prior to adjuvant tamoxifen therapy for breast cancer
      and, furthermore, they should educate patients about signs and symptoms of early
      endometrial carcinoma and when reported these should be followed up with a
      gynecologic examination.

PMID- 9764863
TI  - Serum CA 125 and first trimester abortion.
AB  - OBJECTIVE: The study was carried out to assess the clinical value of serum CA 125
      in association with serum beta-human chorionic gonadotropin (hCG) for predicting
      pregnancy outcome. METHODS: One hundred spontaneous pregnancies, 52 non
      threatened pregnancies and 48 with threatened abortions, observed in the
      Department of Obstetrics and Gynecology at the University 'La Sapienza', Rome,
      Italy, were evaluated during the first trimester using ultrasound examination, CA
      125 and beta-hCG titrations. RESULTS: Threatened pregnancies had statistically
      significantly higher CA 125 serum values than non-threatened pregnancies,
      especially those with a negative outcome (P < 0.01). The CA 125 levels in the
      threatened pregnancies were positively correlated with the tropho-decidual
      hematoma volume (r=0.839, P < 0.0001). The CA 125-beta-hCG association showed a
      higher prognostic value (sensitivity 78.9%, specificity 96.5%) in assessing
      pregnancy outcome than CA 125 or 0-hCG alone (sensitivity 78.9% and 57.9%,
      respectively; specificity 75.8% and 86.2%, respectively). CONCLUSIONS: Our
      findings are in accordance with the hypothesis of a tropho-decidual origin of
      this marker, suggesting its possible usefulness in the prognostic evaluation of
      first trimester threatened abortion.

PMID- 9764864
TI  - Oral nifedipine therapy in the management of severe preeclampsia.
AB  - OBJECTIVE: The purpose of this study was to compare the efficacy of nifedipine
      (Cordipin) and hydralazine in lowering blood pressure in severe preeclampsia.
      METHOD: A randomized, prospective study of 104 patients with severe preeclampsia
      in the Department of Obstetrics and Gynecology, Korle-Bu Teaching Hospital,
      Accra, Ghana, was conducted between January 1992 and June 1994. RESULTS: Of the
      104 patients recruited into the study, six did not deliver at our hospital and
      were thus excluded from the study. Nifedipine and hydralazine as first-line drugs
      controlled the blood pressure in 44 and 35 patients, respectively, but failed in
      5 and 14, respectively. This was statistically significant (P < 0.05). The mean
      birth weight was higher in the nifedipine group (2500+/-800 g vs. 2400+/-800 g).
      There were 11 admissions to the neonatal intensive care unit in the nifedipine
      group and 13 in the hydralazine group but the difference was not statistically
      significant. CONCLUSION: Nifedipine and hydralazine could both be used
      effectively to control blood pressure in severe preeclampsia in our subregion.
      While hydralazine is administered intravenously and needs strict monitoring,
      nifedipine is more effective, is easy to administer orally, less demanding on
      hospital staff, convenient and more predictable.

PMID- 9764865
TI  - Urogenital infection in preeclampsia.
AB  - OBJECTIVE: The purpose of this study was to determine whether the incidence of
      urinary tract infections and postpartum endometritis were increased in
      preeclamptic pregnancies. METHOD: We conducted a retrospective study of 13852
      pregnant women, using a perinatal database at The Johns Hopkins Hospital, over
      the past 5 years. The incidence of urinary tract infections and postpartum
      endometritis was analyzed using the chi-squared test and logistic regression
      analysis. Statistical significance was set at P < 0.05. RESULTS: There were 345
      (2.5%) mild preeclamptics and 440 (3.2%) severe preeclamptics. The incidence of
      urinary tract infections and postpartum endometritis in preeclamptic patients was
      significantly higher than that in non-hypertensive pregnant patients. After
      controlling for confounding variables, severe preeclampsia was still found to be
      an independent significant risk factor for both urinary tract infections and
      postpartum endometritis. CONCLUSION: Our data show a significant increase in
      urogenital infection in preeclamptic pregnancy. This may reflect higher rates of
      underlying renal disease and placental bed abnormalities occurring in
      preeclampsia.

PMID- 9764866
TI  - Electromyographic activity in cervices with very low Bishop score during labor.
AB  - OBJECTIVES: To investigate the activity of the smooth muscles in the cervix at
      the onset of induced labor and to further elucidate this activity in relation to
      uterine contractions and to the duration of the latent phase of labor, taking
      cervical ripeness into account. METHODS: Cervical electromyographic (EMG)
      activity was studied at the onset of labor induced with amniotomy and oxytocin.
      Bipolar measurement of cervical electrical activity was performed. The root mean
      square of the cervical EMG activity and the intensity of intrauterine pressure in
      two groups of parturients with different cervical ripeness were compared.
      RESULTS: The EMG activity was higher in the group with lower Bishop scores. We
      found a significant positive correlation between EMG activity and duration of the
      latent phase of labor. CONCLUSION: Smooth muscles in the human cervix are active
      during labor and act to some extent independently of the uterine corpus.

PMID- 9764867
TI  - Free alpha-subunits of human chorionic gonadotropin in preeclampsia.
AB  - OBJECTIVE: To investigate free alpha-human chorionic gonadotropin (hCG) as a
      marker of preeclampsia. METHODS: Four groups of patients were studied: normal
      pregnancies, preeclampsia, eclampsia and normal pregnant women <20 weeks'
      gestation. Patients were further divided according to parity and gestational age
      (< or =20, 21-30, 31-40 weeks). An immunoradiometric assay employing monoclonal
      antibodies specific for free alpha-hCG was used. RESULTS: A total of 313 patients
      were analyzed. Thirty-four patients < or =20 weeks' gestation were followed until
      delivery: five (14.7%) developed preeclampsia; none had abnormal alpha-hCG levels
      before onset of preeclampsia. Patients with preeclampsia (21-30 weeks' gestation)
      demonstrated a mean alpha-hCG level greater than that of normotensive controls
      but this was not statistically significant. Between 31 and 40 weeks' gestation,
      mean alpha-hCG levels in the hypertensive and control groups were 210.8 ng/ml and
      115.8 ng/ml, respectively (P < 0.001). A stronger association was observed
      between alpha-hCG and preeclampsia with increasing gestational age (relative risk
      [RR] 2.07, 21-30 weeks; RR 3.02, 31-40 weeks) and severity (RR 4.51, mild; RR
      12.15, severe; RR 16.88, eclampsia). CONCLUSION: There is a strong association
      between alpha-hCG and preeclampsia, nevertheless this test is unsuitable for
      predicting preeclampsia.

PMID- 9764868
TI  - Magnesium sulfate as an anticonvulsant in eclampsia.
AB  - OBJECTIVE: To examine the efficacy of magnesium sulfate (MgSO4) as an
      anticonvulsant in eclampsia and imminent eclampsia. METHODS: Case records of 562
      consecutive patients with eclampsia and 174 with imminent eclampsia treated at
      the Institute of Obstetrics and Gynaecology, Hyderabad, India, during the 3-year
      period from January 1987 to December 1989, were reviewed. Management consisted
      of: (1) MgSO4 to control convulsions; (2) sublingual nifedipine to control
      hypertension; and (3) delivery of the fetus. RESULTS: Convulsions were controlled
      in 95% of cases with the initial dose of magnesium and within half an hour in a
      further 2%. Cesarean section was performed mainly for obstetric indications.
      Depression of knee jerks was found to be the first sign of impending magnesium
      toxicity and with the precautions observed, magnesium toxicity was negligible.
      Maternal mortality was 2.4% (18 maternal deaths) and perinatal mortality 36% (247
      perinatal deaths). Sixteen women with eclampsia (2.8%) and two with imminent
      eclampsia (1.1%) died. Of the 247 perinatal deaths, 61 were in the category of
      imminent eclampsia. There were 10 sets of twins. Cerebrovascular accident was the
      leading cause of maternal death. Fetal deaths and prematurity were important
      causes of perinatal loss. CONCLUSIONS: The control of convulsions is the most
      important aspect in the management of eclampsia, and MgSO4 is a very effective
      anticonvulsant.

PMID- 9764870
TI  - Interleukin-1 receptor antagonist expression in epithelial cells of human
      endometrium.
AB  - OBJECTIVE: To examine the expression of interleukin-1 (IL-1) and IL-1 receptor
      antagonist (IL-1ra) in the human endometrium in the follicular and luteal phases.
      METHODS: The concentrations of IL-1alpha and IL-1beta in the culture supernatants
      of endometrial cells were determined by enzyme-linked immunosorbent assay.
      Transcription of the IL-1ra gene in the endometrium was investigated by reverse
      polymerase chain reaction (PCR). Human endometrium was immunohistochemically
      stained using a monoclonal antibody specific to IL-1ra. RESULTS: The
      concentrations of IL-1alpha and IL-1beta in the culture supernatants were 11 and
      55 pg/ml, respectively, in the follicular phase, and 10 and 40 pg/ml,
      respectively, in the luteal phase. The concentration of IL-1ra was 465 pg/ml in
      the follicular phase and 1710 pg/ml in the luteal phase. Densitometric analysis
      of the reverse PCR products showed that the expression of IL-1ra mRNA was
      increased in endometrial cells in the luteal phase. Immunohistochemical staining
      revealed that epithelial cells were the main source of IL-1ra in human
      endometrium. CONCLUSIONS: Human endometrial cells produce IL-1 (mainly IL-1beta)
      and IL-1ra. The level of IL-1ra production in human endometrial epithelial cells
      was greater in the luteal phase than in the follicular phase due to the increased
      transcription of the IL-1ra gene.

PMID- 9764869
TI  - The effect of regular exercise on women receiving danazol for treatment of
      endometriosis.
AB  - OBJECTIVE: To determine the effects of regular exercise on women receiving
      danazol for the treatment of endometriosis. METHODS: Thirty-nine patients were
      randomized to a danazol-only or a danazol/exercise regimen in a prospective
      clinical trial carried out at tertiary care institutions. Patients in the
      danazol/exercise group were instructed to exercise four times per week, for 40
      min per session, at an intensity of 20 metabolic units. Side effect profiles,
      pelvic symptoms, aerobic fitness, strength and hormone levels were compared for
      all subjects. The number of side effects of danazol was analyzed by the method of
      generalized estimating equations. RESULTS: The number of side effects reported
      during a 4-week period was 1.09-2.17 times greater for the danazol-only than for
      the danazol/exercise group. All patients had improvement of symptoms during
      treatment. The danazol/exercise group had significantly lower testosterone levels
      during treatment. The time to recurrence of endometriosis was not different
      between groups. CONCLUSIONS: Exercise during danazol therapy reduces the number
      of androgenic side effects. Relief of pain and time to recurrence are unaffected.

PMID- 9764871
TI  - Laparoscopic para-aortic lymph node sampling in the staging of invasive cervical
      carcinoma: including a comparative study of 21 laparotomy cases.
AB  - OBJECTIVES: To assess the efficacy and risks of laparoscopic para-aortic lymph
      node sampling compared with standard laparotomy in staging cervical carcinoma.
      METHODS: From August 1993 through July 1994, 38 patients with biopsy-proven
      invasive cervical carcinoma (24 early and 14 advanced invasive cancers) were
      entered into the study. This was a prospective study of laparoscopic para-aortic
      lymphadenectomy in invasive cervical carcinoma, with patients serving as their
      own controls. Video laparoscopic lymph node sampling was performed. In patients
      with early invasive cancer, the nodes were sent for frozen section and, if
      negative, laparotomy was performed to look for any residual nodes. Radical
      hysterectomy was performed immediately if residual nodes were negative. Patients
      with either nodal metastasis on frozen section or with advanced cancer underwent
      para-aortic lymphadenectomy only. The operative technique was also evaluated.
      RESULTS: Laparoscopy required an average of 77 min (S.D. 40), with an average
      blood loss of 116 ml (S.D. 321). The average number of nodes was 15 (S.D. 7). At
      subsequent laparotomy the average number of residual nodes found was 0.4 (S.D.
      0.9) and none showed metastasis. One vena cava laceration and one ureteral injury
      required immediate repair, and two patients were too obese to undergo
      laparoscopy. CONCLUSIONS: Laparoscopic para-aortic lymph node sampling is a less
      invasive, reliable method for staging invasive cervical carcinoma and can
      substitute for traditional open procedures. The incidence of risks with this
      method appears to be low.

PMID- 9764872
TI  - Pregnancy and its outcome in quadriplegia due to Pott's spine.
AB  - Pregnancy with quadriplegia is a problem sometimes encountered in obstetric
      practice. The etiology of quadriplegia in the developed world is mainly spinal
      cord tumor or accident, while in the developing countries the main cause is
      tuberculosis of the spine. We report the management of two pregnant patients with
      quadriplegia due to tuberculosis of the cervical spine. Worsening of the
      neurological condition necessitated early surgical intervention, and termination
      of pregnancy was advised in both patients. Literature on the subject makes
      frequent reference to the life-threatening complication of autonomic
      hyperreflexia encountered during pregnancy and delivery. It is characterized by
      sweating, headache, severe hypertension leading to unconsciousness and
      convulsions. These complications, surprisingly, were absent in both of our
      patients.

PMID- 9764873
TI  - Echinococcosis of the liver during pregnancy.
AB  - A 20-year-old Turkish woman with three huge echinococcus cysts of the liver was
      admitted in the third trimester of pregnancy. During pregnancy she received
      albendazole and during vaginal delivery she received both albendazole and
      medication aimed at preventing anaphylactic reaction. We believe that the
      presence of large hydatid cysts during pregnancy should be managed conservatively
      with courses of albendazole after the first trimester of pregnancy.

PMID- 9764875
TI  - Oral pyogenic granuloma in pregnancy.

PMID- 9764874
TI  - Ultrasonographic appearance of fallopian tube carcinoma.
AB  - Preoperative diagnosis of tubal carcinoma is difficult and a diagnosis cannot
      usually be established until the time of operation. However, since prognosis is
      strictly related to the stage of the neoplasm, it is very important to be
      familiar with the clinical and imaging characteristics of primary fallopian tube
      carcinoma in order to make an early and accurate diagnosis. This report presents
      the ultrasonographic features of three cases of fallopian tube carcinoma and
      reviews the literature on the subject.

PMID- 9764876
TI  - Epiphenomenal antiovarian antibodies in hypogonadotropic hypogonadism.

PMID- 9764877
TI  - Significance of intrauterine gas at postpartum ultrasonography.

PMID- 9764878
TI  - Self-inflicted vaginal bleeding.

PMID- 9764879
TI  - Tuboperitoneal fistula after salpingostomy.

PMID- 9764880
TI  - ACOG technical bulletin. Evaluation and treatment of hirsute women. Number 203 --
      March 1995 (replaces no. 103, April 1987). American College of Obstetricians and
      Gynecologists.

PMID- 9764881
TI  - ACOG committee opinion. Condom availability for adolescents. Number 154 -- April
      1995. Committee on Adolescent Health Care. American College of Obstetricians and
      Gynecologists.

PMID- 9764882
TI  - Influence of breastfeeding and complementary food on growth between 5 and 10
      months.
AB  - The aim of this study was to examine the nature of the association between
      breastfeeding, complementary feeding and growth in a random sample of infants
      from Denmark, where the prevalence of breastfeeding is high. A semiquantitative
      food frequency questionnaire and a questionnaire on breastfeeding duration and on
      weight and length measurements taken at the infant welfare visit at 5 and 10
      months were sent to 590 families with 10-month-old infants. A total of 339
      infants with complete growth data were included in the analyses. When controlling
      for mid-parental height and birth weight infants breastfed for > or =7 months
      gained 198 g less in weight (p < 0.01) and 7 mm less in length (p < 0.01) during
      the period from 5 to 10 months than infants breastfed for < 7 months. Controlling
      for these effects, the 10% of the sample with the highest protein intake (i.e. >
      or =16 energy percentage) gained 262 g more than those with a lower protein
      intake (p = 0.03). Infants breastfed for > or =7 months received significantly
      less cow's milk (p < 0.01), and fewer meat-containing dishes (p < 0.05) and
      sweets or cakes (p < 0.01), which may partly explain the effect of breastfeeding.
      The long-term consequences of this moderate difference in growth velocity are
      unknown and the findings should not be used to advocate against breastfeeding
      during late infancy.

PMID- 9764883
TI  - High-density lipoprotein subclasses and esterification rate of cholesterol in
      children: effect of gender and age.
AB  - Since the development of coronary heart disease (CAD) is affected by a specific
      pattern of plasma high density lipoprotein (HDL) effects it may be useful to know
      whether this occurs already in childhood. In this study we evaluated particle
      size distribution of HDL by gradient gel electrophoresis and the determination of
      cholesterol esterification rate (FER(HDL)) in plasma depleted of apo B
      lipoproteins in 221 children (108 boys and 113 girls) aged 4 months to 20 years.
      Total plasma- (TC), low-density lipoprotein- (LDL-C) and HDL- (HDL-C)
      cholesterol, HDL unesterified cholesterol (HDL-UC) and plasma triglycerides (TG)
      were also measured. There were no significant gender and age differences with
      respect to the plasma TC, LDL-TC and TG but concentration of HDL-TC increased
      with age. Post-pubertal girls had significantly higher relative concentrations of
      HDL2b compared to boys (30.4% vs 17.2%), while HDL3b,c was lower in post-pubertal
      girls (8.7% vs. 16.5%). FER(HDL) correlated inversely with HDL2b and positively
      with HDL3b,c particles and was significantly higher in boys of the post-pubertal
      group compared to girls (16.9%/h vs 12.5%/h). While in girls there was a positive
      correlation between age and HDL-C, HDL-UC and the relative concentration of HDL2b
      no significant correlation were observed in boys. In girls the increase in TC
      showed a significant correlation with a simultaneous increase in HDL-C, HDL-UC
      and HDL2b. In boys TC correlated significantly with changes in TG only. When
      HDL2b and HDL3b,c cholesterol levels are calculated from HDL-C concentration and
      per cent distribution the differences between males and females are further
      emphasized. These data indicate that HDL particle size distribution is age- and
      gender-dependent.

PMID- 9764884
TI  - Dual energy X-ray absorptiometry of the hand and wrist--a possible technique to
      assess skeletal maturation: methodology and data in normal youths.
AB  - Ninety five normal Caucasian subjects (51F, 44M) aged from 2 to 25 y were
      measured at the hand and wrist level with a small DXA system (pDEXA) in order to
      obtain the normal values of the bone mineral content (BMC), density (BMD) and
      projected area (A) of carpal (c) and metacarpal (m) bones. BMDc ranged from 0.065
      +/- 0.007 g/cm2 to 0.365 +/- 0.035 g/cm2 in females and 0.425 +/- 0.040 g/cm2 in
      males. It presented a sharp change of increase rate at 15.5 and 17 y of age in
      girls and boys, respectively. Ac presented the same kind of evolution as BMDc,
      but had a larger value dispersion. The second metacarpal bone had the highest
      BMCm value in 85% of females and 90% of males. The sum of BMCmi or Ami values (i
      = 1-5) and the projected mean density of the 5 metacarpal bones was well
      correlated with BMCc, Ac and BMDc, respectively (r > 0.90). A volumetric mineral
      density, dmi, calculated for each of these bones, approximated to a cylinder, was
      correlated with age (r > 0.85).

PMID- 9764885
TI  - Diurnal rhythm of serum osteocalcin in normal children.
AB  - The aim of the present study was to assess diurnal levels of serum osteocalcin in
      normal children using a recently introduced fluoroimmunoassay (Pharmacia
      Osteocalcin CAP FEIA) measuring solely the intact peptide. Five girls and two
      boys aged 10.4-13.6 (mean 12.2) y were studied. Blood samples for determination
      of osteocalcin were collected every 2h throughout the day. A statistically
      significant rise in serum osteocalcin (F = 6.7, p < 0.001) with a peak at 08.00 h
      and a nadir lasting from 10.00 to 24.00 h was found. Trough and peak levels (at
      16.00 and 08.00 h, respectively) were 41.6 +/- 6.8 and 66.0 +/- 10.5 microg l(-1)
      (mean +/- SEM). The circadian variation should be taken into consideration when
      single assessments of serum osteocalcin in children are performed.

PMID- 9764886
TI  - Lymphocyte subsets and cytokines in adenoviral infection in children.
AB  - To determine the distribution of major blood lymphocyte subsets we evaluated
      blood lymphocytes by flow cytometry in adenovirus-infected infants aged 30-730 d.
      In addition, interleukin-1-receptor antagonist, interleukin-10 and transforming
      growth factor-beta1 were measured in serum by enzyme-linked immunosorbent assay.
      According to clinical parameters, mechanical ventilation and outcome, infections
      were classified as moderate (n = 15), severe (n = 11) and fatal (n = 12).
      Controls were 13 healthy children. In severe and fatal infection, T cells
      (CD5+/CD19-), NK effectors (CD16+), CD4+ T subset and B1 subset of B lymphocytes
      (CD5+/CD19+) were all significantly decreased. CD8+ cells were decreased in
      severe but not fatal cases. There was no difference in serum values of
      interleukin-10; however, fatal cases had high interleukin 1-receptor antagonist
      values. Interestingly, patients with moderate infection showed significantly
      increased values of transforming growth factor-beta1. These results demonstrate
      that life-threatening adenoviral infection is associated with marked
      abnormalities in blood lymphocyte and cytokine profile.

PMID- 9764887
TI  - Streptococcus pneumoniae isolated from a paediatric population: changes in 10
      years.
AB  - Susceptibility to penicillin, cefotaxime, erythromycin and chloramphenicol, as
      well as serotypes of 100 Streptococcus pneumoniae strains isolated between 1984
      and 1985, were compared to those of the same number of strains isolated between
      1994 and 1995. The strains were obtained in Hospital Sant Joan de Deu, Barcelona,
      and were thought to be the cause of a variety of infectious diseases in
      paediatric patients attending this centre. Minimal inhibitory concentrations
      (MICs) of penicillin were higher in strains of the second period (51% of
      resistant strains during the first period vs 61% during the second one), as were
      those of cefotaxime (12% vs 18%) and erythromycin (6% vs 36%), while
      chloramphenicol MICs showed a light decrease (65% vs 46%). Serotypes 6, 19 and 23
      were the most prevalent. Five new serotypes (4, 10, 18, 22 and 31) were detected
      in 10 penicillin-susceptible strains during the second period. Because of the
      increase in resistance to antibiotics commonly used in the treatment of systemic
      and localized infections, therapeutic alternatives must be studied and suggested
      in order to offer oral and percutaneous treatment for our children's infections
      caused by pneumococci.

PMID- 9764888
TI  - Open lung biopsy--successful diagnostic tool with therapeutic implication in the
      critically ill paediatric population.
AB  - Open lung biopsy (OLB) is an important diagnostic tool in children with immune
      deficiency and/or chronic lung disease with diffuse pulmonary compromise. These
      patients require a tailored therapeutic approach owing to their fragile status
      and the side effects of unnecessary or inadequate treatment. Twenty-six patients
      of mean age 5.6 y underwent 41 open lung biopsies in our centre between 1991 and
      1995. Seventeen (65%) were immunocompromised (including 13 with malignancy) and 9
      had other lung diseases. The biopsies were diagnostic in 25 patients (96%), and
      complete clinical-pathological correlation was found in 11 (42%). A specific
      infectious aetiology was detected in nine patients (35%), all of them
      immunocompromised. Therapeutic changes were instituted on the basis of the biopsy
      findings in 18 patients (69%). Two patients had postoperative complications
      (prolonged pleural leak). We conclude that OLB is a safe diagnostic procedure
      even in the critically ill child and should be employed without hesitation when
      conventional methods fail to provide a definitive diagnosis to help redirect
      therapy.

PMID- 9764889
TI  - Renal impairment in patients with long-standing cyanotic congenital heart
      disease.
AB  - Nephropathy is known to occur in patients with long-standing cyanotic congenital
      heart disease (CCHD). In order to assess the incidence, nature and degree of the
      problem among such patients, discriminating urine analyses were performed in 26
      patients with CCHD, with a mean age of 22 (10-42) y. Ten patients showed reduced
      glomerular function, six of whom also had advanced glomerulopathy. Glomerular
      filtration rates were below normal in half of the patients and occurred with
      glomerular-type proteinuria in five, with tubular-type proteinuria in one and
      without pathological proteinuria in four. An elevated haematocrit and duration of
      cyanosis were identified as the main risks factors for the development of
      glomerulopathy. The risk of developing glomerular lesions rose sharply during the
      second decade of life. Nephropathy in CCHD is common and the dominant feature is
      glomerular damage, which is related to the duration of cyanosis and the extent to
      which the haematocrit is elevated.

PMID- 9764890
TI  - Effect of umbilical arterial catheters on intestinal blood supply.
AB  - Umbilical arterial catheters in the high position reduce the lumen of the aorta
      and may thereby impair blood supply to the intestine. Thirty-two preterm and
      three term infants were studied with an umbilical arterial catheter by colour and
      duplex Doppler sonography. The diameter of the aorta at the level of the coeliac
      axis was measured to calculate the reduction of the cross-sectional area of the
      aorta by the catheter. Blood-flow velocities were measured in the coeliac axis,
      the superior mesenteric artery and the anterior cerebral artery before and after
      removal of the catheter. The umbilical arterial catheter reduced the cross
      sectional area of the aorta by 3.4-27.2% (mean 10.1%). There was no difference
      between blood-flow velocities in the coeliac axis and the superior mesenteric
      artery before and after removal of the umbilical arterial catheter, indicating
      that the catheter did not impair blood supply to the intestine.

PMID- 9764891
TI  - Vitamin K in preterm breastmilk with maternal supplementation.
AB  - Six healthy lactating mothers who gave birth to preterm infants at a median post
      conceptional age of 29.5 (range 26-30) weeks were given 2.5 mg phylloquinone
      (vitamin K1) orally daily for 2 weeks beginning at a median postconceptional age
      of 31.5 (range 28-32) weeks. Phylloquinone was measured in the breastmilk daily
      for 14 d. Trough plasma phylloquinone concentrations were also determined on four
      occasions. Phylloquinone levels in the breastmilk increased from a baseline of 3
      +/- 2.3 ng ml(-1) to 22.6 +/- 16.3 ng ml(-1) (mean +/- SD) after the first dose
      (p < 0.05); a gradual increase was noted until phylloquinone levels reached a
      plateau of 64.2 +/- 31.4 ng ml(-1) after the sixth daily dose.

PMID- 9764892
TI  - "Idiopathic neutropenia" in very low birthweight infants.
AB  - We employed a standardized investigative approach to evaluate four cases of
      "idiopathic neutropenia" in very low birthweight infants. The evaluation included
      maternal anti-neutrophil antibodies, a marrow aspiration, and a three-day trial
      of recombinant granulocyte colony-stimulating factor (rG-CSF). All patients had
      neutropenia at or shortly following delivery, and remained neutropenic (generally
      <500/microl) for 1-9 weeks until rG-CSF was administered. Blood and bone marrow
      studies in all 4 indicated that the neutropenia was: (i) the kinetic result of
      diminished neutrophil production; (ii) not alloimmune; (iii) not cyclic; and (iv)
      not associated with recognized inborn errors, bacterial or viral infections, or
      medications. All responded to rG-CSF by transiently increasing their blood
      neutrophils to normal, and the neutropenia resolved in all cases with time. It is
      likely that "idiopathic neutropenia" in this population represents a common
      phenotype of several different causes, rather than a single entity. Some cases,
      perhaps the majority, will respond to a short course of rG-CSF administration.

PMID- 9764893
TI  - Artificial neural network for predicting intracranial haemorrhage in preterm
      neonates.
AB  - Intraventricular haemorrhage (IVH) incidence is used to assess peri-/neonatal
      therapy, and to make intra- and inter-hospital quality assessments. Unbiased
      assessment is complicated by the amount of confounding factors. Is an artificial
      neural network (ANN) able to early and accurately forecast the occurrence of
      severe IVH in an individual patient? Is it superior to classic multiple logistic
      regression? We conducted an observational study on pre-existing routine data.
      Admission data were available from 890 preterm neonates (gestational age < 32
      weeks, birthweight < 1500 g). Patients were randomly assigned to either a
      training, or a validation set (50%/50%). Using the training set data an ANN was
      trained. A second predictive model was developed by stepwise multiple logistic
      regression analysis. Using the validation set input data both models delivered
      estimates of the probability for severe IVH to occur in each individual patient.
      Receiver operating characteristic (ROC) curves were used to compare prognostic
      performance. The optimal ANN processed 13 input variables, whereas stepwise
      logistic regression analysis only identified five independent predictor
      variables. The area under the ROC curve was 0.935 for the ANN and 0.884 for the
      logistic regression model (p = 0.001). Adjusted for 95%, 90%, 85%, 80% and 75%
      specificity, the sensitivity of the ANN was significantly superior to that of the
      logistic regression model. Due to its ability to give an accurate prognosis based
      solely on admission data, a trained ANN qualifies as a tool for local quality
      control.

PMID- 9764894
TI  - Kangaroo mother care for low birthweight infants: a randomized controlled trial
      in different settings.
AB  - A randomized controlled trial was carried out for 1 y in three tertiary and
      teaching hospitals, in Addis Ababa (Ethiopia), Yogyakarta (Indonesia) and Merida
      (Mexico), to study the effectiveness, feasibility, acceptability and cost of
      kangaroo mother care (KMC) when compared to conventional methods of care (CMC).
      About 29% of 649 low birthweight infants (LBWI; 1000-1999 g) died before
      eligibility. Of the survivors, 38% were excluded for various reasons, 149 were
      randomly assigned to KMC (almost exclusive skin-to-skin care after
      stabilization), and 136 to CMC (warm room or incubator care). There were three
      deaths in each group and no difference in the incidence of severe disease.
      Hypothermia was significantly less common in KMC infants in Merida (13.5 vs 31.5
      episodes/100 infants/d) and overall (10.8 vs 14.6). Exclusive breastfeeding at
      discharge was more common in KMC infants in Merida (80% vs 16%) and overall (88%
      vs 70%). KMC infants had a higher mean daily weight gain (21.3 g vs 17.7 g) and
      were discharged earlier (13.4 vs 16.3 d after enrolment). KMC was considered
      feasible and presented advantages over CMC in terms of maintenance of equipment.
      Mothers expressed a clear preference for KMC and health workers found it safe and
      convenient. KMC was cheaper than CMC in terms of salaries (US$ 11,788 vs US$
      29,888) and other running costs (US$ 7501 vs US$ 9876). This study confirms that
      hospital KMC for stabilized LBWI 1000-1999 g is at least as effective and safe as
      CMC, and shows that it is feasible in different settings, acceptable to mothers
      of different cultures, and less expensive. Where exclusive breastfeeding is
      uncommon among LBWI, KMC may bring about an increase in its prevalence and
      duration, with consequent benefits for health and growth. For hospitals in low
      income countries KMC may represent an appropriate use of scarce resources.

PMID- 9764895
TI  - Community-based survey of paediatric diarrhoeal morbidity and home treatment
      practices in Finland.
AB  - To determine total diarrhoeal morbidity and current home case management
      practices, a recall study was conducted among 345 mothers whose 406 children
      under 5 y of age had had diarrhoea in the past 4 months. The seasonally adjusted
      annual diarrhoea incidence rate was 0.48 episodes/child/y. For home treatment,
      increased amounts of fluid were given in 93% and oral rehydration solution (ORS)
      in 37% of cases. However, when given, ORS was diluted with other fluids in 41% of
      cases. More than half (55%) of the children received increased or normal amounts
      of food during the diarrhoeal episode, but 7% of the children were kept fasting
      for at least 1 d. Use of antidiarrhoeal drugs was minimal (0.7%), but products
      containing lactic acid bacteria were given in 44% of cases. Case management
      practice in cases of diarrhoea at home have much improved during the last 20 y,
      but are still not optimal.

PMID- 9764896
TI  - Chlorinated contaminants, growth and thyroid function in schoolchildren from the
      Aral Sea region in Kazakhstan.
AB  - It has been shown by others that offspring of mothers who had been exposed to
      dioxins and polychlorinated biphenyls (PCBs) during pregnancy have elevated
      plasma levels of thyroid-stimulating hormone (TSH) for at least 3 months after
      birth and reduced plasma levels of free and total thyroxine during the second
      week after birth. As elevated levels of dioxins and PCB s can thus alter thyroid
      hormone status, the relation between the levels of some polychlorinated organic
      compounds in the blood lipids and growth and thyroid hormone status was studied
      in 12 hospitalized schoolchildren from the Aral Sea region known to have high
      exposure to such compounds. Their level of PCBs was two to four times higher than
      in healthy Stockholm children. Their height was found to be lower than in healthy
      Swedish children of the same age mean (SDS -0.52) and the body mass index (BMI)
      was inversely correlated to the total concentrations of PCBs and
      dichlorodiphenyltrichloroethane (DDT) and its metabolite
      dichlorophenyldichloroethylene (DDE) in the blood lipids. As the levels of
      insulin-like growth factor- were reduced to the same extent as the BMI it seems
      likely that PCBs and DDT cause malnutrition as a result of malabsorption. None of
      the children had any impairment of thyroid function, as revealed by the plasma
      levels of TSH and thyroxine. Although the concentrations of beta
      hexachlorocyclohexane (beta-HCH) and DDE were extremely high in some of the
      children there was no relation between thyroid hormone status and the blood lipid
      levels of PCBs, hexachlorocyclohexane and DDT. However, the concentration of
      dioxins was not analysed.

PMID- 9764897
TI  - Utilization of Child Health Services during the first 18 months of life: aspects
      of health surveillance in Swedish preschool children based on information in
      health records.
AB  - The aim of this study was to evaluate some aspects of care given within the
      preventive Child Health Services (CHS) during the first 18 months of life. A
      national random sample performed on child health records of 172 Swedish preschool
      children born between 1982 and 1987 was analysed regarding services recorded as
      having been provided and used within and beyond the national programme of health
      surveillance. Most families had made visits within the core programme of health
      surveillance to an optimal or at least sufficient extent. First-time parents
      visited the CHS more frequently than did more experienced parents. Procedures
      within the programme, such as growth monitoring, hip examination and
      immunizations, were documented to have been optimally performed on a majority of
      the children. Conversely, screening for hearing impairment and assessment of
      developmental milestones were performed less frequently, as were health
      information and postnatal parental education. To improve the quality of care,
      national recommendations ought to be more specific regarding both the performance
      and the documentation of the service.

PMID- 9764898
TI  - Changes in day care attendance rates and in the occurrence of adenoidectomies and
      tympanostomies.
AB  - The care of a child in a day care center is a marked risk factor for acute otitis
      media. In a nationwide questionnaire survey we found that the rate of
      tympanostomies and adenoidectomies was 59-67% higher for the children cared for
      at a day care center before the age of 3 y. When the local authorities in Finland
      at the beginning of 1990 were obliged by law to arrange day care for all children
      under 3 y, the number of adenoidectomies performed on children at this age
      increased by 30%.

PMID- 9764899
TI  - Prone position may increase temperature around the head of the infant.
AB  - Recommendations to adopt the supine position were followed by a dramatic decrease
      of SIDS. But no explanation has been given for the association between SIDS and
      the prone position nor for its decrease in the supine position. We report data on
      an infant and a mannequin demonstrating an increase in temperature around the
      head in the prone position. A 4-month-old boy presented an acute life-threatening
      event related to temperature after febrile otitis despite treatment: 40.5 degrees
      C, heart rate 280 bpm with circulatory failure and cardiorespiratory arrest
      requiring resuscitation. There were no seizures. Blood and CSF cultures were
      negative. The course under antibiotics was favourable. On d 3, we measured
      temperature at several sites on and around the heat. Temperatures were higher in
      the prone than in the supine position in pericephalic areas: +1 degrees C
      (supracephalic), +2.5 degrees C (peritemporal), and +3.5 degrees C
      (submandibular). In a thermoregulated room, we used a mechanically ventilated
      mannequin of an infant. The prone position was also associated with an increase
      in temperature around the head: +3.3 degrees C (supracephalic), +1.8 degrees C
      (peritemporal), and +1.1 degrees C (submandibular). Changing from the supine to
      prone position thus increased temperature around the head (infant and mannequin).
      To our knowledge, this has not been reported before. SIDS is related to factors
      modifying temperature status and environment. Furthermore, evacuation of heat is
      mandatory for an infant. We think the increase in temperature around the head in
      the prone position is due to the absence of convective fluxes, and speculate it
      could impair thermolysis.

PMID- 9764900
TI  - A case of vertical transmission of hepatitis A virus infection.
AB  - We present a case of hepatitis A infection in a 2.5-month-old male who became
      icteric after 18 d of birth. The diagnosis of hepatitis A was made by compatible
      clinical symptoms, laboratory results and liver biopsy showing evidence of
      hepatitis, and confirmed by detection of anti-HAV IgM antibodies. Because the
      mother had an acute icteric hepatitis A 1 week before delivery, and the viraemic
      phase of hepatitis A infection is very short, approximately 7 d, we suggest that
      the infant was infected by his mother, before birth.

PMID- 9764901
TI  - Congenital chylothorax in siblings.
AB  - We describe two cases of congenital chylothorax in siblings with important
      differences from previously described familial cases. Our findings support the
      likelihood of an autosomal recessive inheritance in some cases of this condition,
      rather than X-linked recessive inheritance, which has also been suggested.
      Autopsy findings from one of these cases and others previously described suggest
      that the pathophysiological mechanisms involved may be variable.

PMID- 9764903
TI  - Is Chlamydia pneumoniae responsible for disease in children?

PMID- 9764902
TI  - Rhabdomyolysis in European viper bite.
AB  - The case of a child who presented with severe rhabdomyolysis associated with
      renal failure after a viper bite is reported. Rhabdomyolysis is a serious
      complication resulting from systemic envenomation and is uncommon after viper
      bites in Europe. It may be due to oedema, myotoxic agents and haemorrhagic
      factors and may be responsible for two types of potentially fatal complications,
      i.e. acute renal failure and hyperkalaemia. The present case highlights the need
      to investigate routinely for rhabdomyolysis after viper bites. Antivenom therapy
      is recommended as soon as signs of envenomation are present, without waiting for
      the onset of complications.

PMID- 9764904
TI  - Long-term nonprogression in HIV infection: methodological issues and scientific
      priorities. Report of an international European community-National Institutes of
      Health Workshop, The Royal Society, London, England, November 27-29, 1995.
      Scientific Coordinating Committee.

PMID- 9764905
TI  - Association between a defective CCR-5 gene and progression to disease in HIV
      infection.
AB  - We measured the effect(s) of CCR-5 genotype on disease progression by studying
      the frequency of a defective CCR-5 delta32 allele within a cohort of long-term
      infected individuals. An elevated frequency of CCR-5 delta32 heterozygotes within
      the cohort compared with a control population of blood donors was observed. An
      association between progression rate and CCR-5 delta32 heterozygosity was
      observed. Furthermore, analysis of proviral DNA V3 sequences from a subset of the
      cohort predicted that the majority of individuals (39 of 44) were infected with
      viruses predicted to utilize the beta-chemokine receptor CCR-5. The marked
      association between CCR-5 genotype and disease progression observed in this study
      may be a consequence of the predicted low frequency of CXCR-4-utilizing viruses
      present within the selected cohort.

PMID- 9764906
TI  - Primary intestinal epithelial cells can be infected with laboratory-adapted
      strain HIV type 1 NDK but not with clinical primary isolates.
AB  - Infectivities of HIV-1 primary isolates and laboratory-adapted strains were
      compared in primary fetal enterocytes and the colonic epithelial cell line HT29.
      Infection by two laboratory strains, HIV-1 NDK and HIV-1 NDK(A4), which were
      adapted on CEM and HT29 cells, respectively, produced significant amounts of
      virus in both target cell systems. Intestinal cells were resistant to infection
      with HIV-1 primary isolates regardless of their genetic subtype or SI/NSI
      phenotype. Biological properties of analyzed viruses rather than differences in
      cultivation system seem to be responsible for differences between these in vitro
      and ex vivo results.

PMID- 9764907
TI  - Potent inhibition of HIV type 1 replication by an antiinflammatory alkaloid,
      cepharanthine, in chronically infected monocytic cells.
AB  - Cepharanthine is a biscoclaurine alkaloid isolated from Stephania cepharantha
      Hayata and has been shown to have antiinflammatory, antiallergic, and
      immunomodulatory activities in vivo. As several inflammatory cytokines and
      oxidative stresses are involved in the pathogenesis of HIV-1 infection, we
      investigated the inhibitory effects of cepharanthine on tumor necrosis factor
      alpha (TNF-alpha)- and phorbol 12-myristate 13-acetate (PMA)-induced HIV-1
      replication in chronically infected cell lines. Two chronically HIV-1-infected
      cell lines, U1 (monocytic) and ACH-2 (T lymphocytic), were stimulated with TNF
      alpha or PMA and cultured in the presence of various concentrations of the
      compound. HIV-1 replication was determined by p24 antigen level. The inhibitory
      effects of cepharanthine on HIV-1 long terminal repeat (LTR)-driven gene
      expression and nuclear factor kappaB (NF-kappaB) activation were also examined.
      Cepharanthine dose dependently inhibited HIV-1 replication in TNF-alpha- and PMA
      stimulated U1 cells but not in ACH-2 cells. Its 50% effective and cytotoxic
      concentrations were 0.016 and 2.2 microg/ml in PMA-stimulated U1 cells,
      respectively. Cepharanthine was found to suppress HIV-1 LTR-driven gene
      expression through the inhibition of NF-kappaB activation. These results indicate
      that cepharanthine is a highly potent inhibitor of HIV-1 replication in a
      chronically infected monocytic cell line. Since biscoclaurine alkaloids,
      containing cepharanthine as a major component, are widely used for the treatment
      of patients with various inflammatory diseases in Japan, cepharanthine should be
      further pursued for its chemotherapeutic potential in HIV-1-infected patients.

PMID- 9764908
TI  - Replication-defective HIV as a vaccine candidate.
AB  - Live attenuated vaccines prepared from simian immunodeficiency virus (SIV) have
      provided the best protective immunity in challenge experiments. In animals
      vaccinated with attenuated SIV, immune responses may be elicited owing to
      endogenous expression of native SIV proteins and/or antigen presentation in the
      native replication site of virus. However, replication-competent viral vaccines
      raise safety concerns for clinical trials in humans. To ensure the safety and
      maintain the immunogenicity of a live, attenuated vaccine, we have developed a
      replication-defective HIV pseudotyped with vesicular stomatitis virus G protein
      (VSV-G). The polymerase gene of HIV was truncated to construct the replication
      defective HIV. This pseudotyped HIV can infect many cell types, including human
      and simian cells, and undergoes only one round of replication. Furthermore,
      antibody immune response can be detected in mice immunized with VSV-G-pseudotyped
      replication-defective HIV.

PMID- 9764909
TI  - Production and characterization of SIV envelope-specific rhesus monoclonal
      antibodies from a macaque asymptomatically infected with a live SIV vaccine.
AB  - Five rhesus monoclonal antibodies (RhMAbs) were produced by rhesus EBV
      transformation of peripheral blood B cells from a rhesus macaque that had been
      asymptomatically infected with an attenuated, macrophage-tropic SIV strain, 17E
      Cl. These MAbs recognized conformation-dependent epitopes on SIV gp120 and could
      not be mapped using synthetic peptides. All five RhMAbs were able to neutralize
      the vaccine strain and a heterologous isolate, SIV/DeltaB670. The RhMAbs did not
      cross-react with HIV-2; by contrast, four human MAbs derived from an HIV-2
      infected person were broadly cross-reactive with both SIV and HIV-2 gp120s. Cross
      competition analysis indicated that the five RhMAbs could be placed in two groups
      recognizing two nonoverlapping epitopes; while the HMAbs were placed in two
      additional competition groups. Binding of the three group I RhMAbs (1.7F, 3.11B,
      and 1.10A) as well as HMAb 17A was shown to be sensitive to specific amino acid
      alterations in V4 occurring in natural env variants. The results of this study
      demonstrate that RhEBV transformation provides a means to probe rhesus antibody
      responses to SIV infection at the monoclonal level. RhMAbs will allow structural
      and functional studies of envelope glycoprotein determinants that elicit
      protective immune responses against SIV.

PMID- 9764910
TI  - HIV peptide conjugated to heat-killed bacteria promotes antiviral responses in
      immunodeficient mice.
AB  - Enhancement of immunity in the setting of HIV infection is difficult owing to
      loss of functional CD4+ T cells. The MHC class II-deficient mouse (II-/-)
      environment simulates that of the immunocompromised HIV-infected individual,
      since these mice have low CD4+ T cell numbers, defective CD4-dependent responses,
      and are susceptible to opportunistic infection. This strain was used to test
      whether heat-killed Brucella abortus (BA), covalently conjugated to the V3
      peptide of HIV-1 (MN), could elicit anti-HIV responses. V3-BA, but not the T
      dependent antigen V3-KLH, induced high levels of IL-12, IFN-gamma, and IL-10 mRNA
      in both wild-type (WT) and II-/- mice within 24 hr of injection. V3-BA-treated,
      but not V3-KLH-treated, II-/- mice developed serum IgG and IgA anti-V3
      antibodies, with IgG2b and IgG3 as the predominant isotype. Viral neutralization
      studies, using a syncytium inhibition assay, demonstrated that the antibodies
      generated by V3-BA in II-/- mice were capable of neutralizing HIV. These
      experiments demonstrate that a heat-inactivated bacterium such as BA, when used
      as a carrier, can generate a cytokine environment that results in the production
      of neutralizing antiviral antibodies in an immunodeficient host. Such strategies
      could be important in the development of immunotherapies and vaccines for HIV-1
      patients.

PMID- 9764911
TI  - Functional and molecular characterization of human monoclonal antibody reactive
      with the immunodominant region of HIV type 1 glycoprotein 41.
AB  - The immunoreactivity, functional activity, and molecular features of a human
      monoclonal antibody (HMAb), F240, from an HIV-1-infected individual have been
      studied. Flow cytometric analysis demonstrated that F240 is reactive with cells
      infected with a broad range of laboratory isolates but not with uninfected cells.
      Reactivity of F240 is greatly enhanced by preincubation of infected cells with
      soluble CD4, and to a much lesser extent, with F105, an HMAb reactive with the
      CD4-binding site of gp120. This enhancement is temperature dependent, with
      maximum enhancement observed at 37 degrees C, and suggests that the F240 epitope
      may be more accessible after gp120 has bound to CD4 in vivo. Immunoblot analysis
      reveals antigen specificity of F240 for gp41 or its precursor gp160. F240
      specificity is mapped to the immunodominant region of the gp41 ectodomain by
      Pepscan analysis. This epitope has been implicated in eliciting nonprotective
      antibodies that enhance infection in the presence of complement. Consistent with
      this, F240 failed to neutralize laboratory isolates and enhanced viral infection
      in a complement-dependent manner. The F240 VH demonstrates extensive somatic
      mutations compared with the product of its closest homologous germline gene VH3
      3.11. Most amino acid substitutions occur in CDR2, characteristic of an antigen
      driven response, and in FR3, a phenomenon observed in other anti-HIV-1 envelope
      HMAbs. Primary structure analysis of the F240 heavy chain revealed strong
      homology in the CDR domains to an HMAb (3D6) reactive with the same gp41 region,
      which suggests that these HMAbs could define a potential human antibody
      clonotype.

PMID- 9764912
TI  - Molecular characterization of the envelope transmembrane glycoprotein of 13 new
      human immunodeficiency virus type 1 group O strains from six different African
      countries.

PMID- 9764913
TI  - A novel glycoprotein 120 sequence from an HIV type 1 isolate of the A clade
      identified in North Uganda.

PMID- 9764914
TI  - HIV type 1 C2V3 env diversity among Belgian individuals.

PMID- 9764916
TI  - Extreme founder effect in an HIV type 1 subtype A epidemic among drug users in
      Svetlogorsk, Belarus.

PMID- 9764915
TI  - The subtypes of HIV type 1 in Greece.

PMID- 9764917
TI  - Introduction to histology of parasitic platyhelminthes.

PMID- 9764918
TI  - Immunolocalization of schistosome proteins.
AB  - This review discusses some of the recent advances in the characterization of
      potential vaccine molecules against Schistosoma japonicum, utilizing microscopy
      and immunocytochemistry methods. Microscopy has demonstrated the stage-specific
      expression of the muscle protein paramyosin onto the parasite surface, an
      important consideration as a vaccine target. Other potential vaccine component
      proteins examined include glutathione S-transferase (GST) and fatty acid binding
      protein (FABP); although not associated with the adult parasite surface, their
      localization to internal structures such as lipid droplets and regions of the
      female reproductive system have provided valuable insights into the biology of
      the parasite. Localization of the transport protein SGTP (schistosome glucose
      transporter protein) has demonstrated that the protein is more prevalent in the
      juvenile stages of the parasite development. This further highlights the
      diversity of the parasite life cycle. Using both light microscopy and
      transmission electron microscopy, the localization of a number of schistosome
      proteins has demonstrated the functions and significance of these proteins within
      the parasite. Molecular localization studies are crucial in understanding how and
      when a vaccine may work against the organism and may provide insights into which
      can be used in the design of future vaccines.

PMID- 9764919
TI  - Life history specializations of monogenean flatworms: a review of experimental
      and microscopical studies.
AB  - This review illustrates the use of experimental approaches combined with
      microscopy to study the biology of monogenean parasites. Studies of feeding,
      development, reproduction, and systematics have been based on gyrodactylids,
      flatworms infecting teleost fishes. In a contrasting system involving an
      amphibian host in a desert environment, analysis of adaptations to extreme
      conditions has focused on Pseudodiplorchis americanus. The unusual reproductive
      strategies, particularly the interactions between mother and offspring, are
      highlighted for both monogeneans. Species of Gyrodactylus are viviparous,
      maintaining up to three generations of embryos simultaneously in utero, and many
      of their reproductive specializations are related to progenesis. Embryo nutrition
      takes place via a metabolically-active syncytial uterine lining that has close
      association with the parental gut. Microscopy has also proved an essential
      adjunct to molecular studies of speciation and host specificity. P. americanus is
      ovoviviparous and the adaptations for embryo maintenance are unique. The primary
      keratin-type eggshell is replaced by a flexible secondary elastin capsule
      produced by the uterus; parental nutrients are transferred through cytoplasmic
      connections to the developing embryo. TEM has demonstrated unique adaptations of
      P. americanus to its micro-environments, including secretion of tegumental
      vesicles that provide protection from digestive enzymes during migration through
      the host gut. This paper highlights the potential of monogeneans for studies of
      fundamental biological principles.

PMID- 9764920
TI  - Observations on the ultrastructure of the anterior adhesive areas and other
      anterior gland cells in the monogenean Merizocotyle australensis (Monocotylidae)
      from the nasal fossae of Himantura fai (Dasyatididae).
AB  - The anterior adhesive areas of a monocotylid monogenean, Merizocotyle
      australensis (Merizocotylinae), were investigated. They comprise 6 ventral
      apertures in 2 groups of 3 arranged at the anterolateral margins of the head.
      These regions are also well supplied with groups of cilia. Each aperture is 13.8
      to 15.8 microm wide and contains multiple tubular projections that are covered
      with microvilli through which open 2 types of secretory cell ducts that carry
      either rod-shaped or spherical secretory bodies. The gland cell bodies that
      produce these 2 types of secretions co-occur at the anterior end. The 2 types of
      secretory bodies occur adjacent to one another and both are present in the
      extruded adhesive. The membranes of rod-shaped bodies are retained in the
      extruded glue. Rod-shaped bodies are 390 +/- 18 nm wide, at least 10.9 microm
      long, and show 2 types of internal periodic banding: 10.6 nm and 143 +/- 3 nm.
      The spherical vesicles are 130 +/- 6 nm in diameter and are electron-dense. A
      third secretion is present in separate ducts that also open anteriorly but emerge
      through the tegument between the ventral apertures. This secretion does not
      appear to be part of the adhesive secretion. The bodies of the third secretion
      are elongate, electron-dense, and 374 +/- 23 nm long. Inside the "lip" of the
      aperture, general body tegument abuts tegument specific to the aperture. The
      general body tegument is thicker, contains electron-dense vesicles, and has a
      ridged surface devoid of microvilli. Where the 2 kinds of tegument meet, they are
      connected by septate desmosomes.

PMID- 9764921
TI  - Ultrastructure of the protonephridial system of the oncomiracidium of Encotyllabe
      chironemi (Platyhelminthes, Monopisthocotylea).
AB  - In the first electron-microscopic study of the protonephridium of a
      monopisthocotylean oncomiracidium, flame bulbs, capillaries, and excretory
      bladders of larval Encotyllabe chironemi were examined. Flame bulbs are formed by
      a terminal and a proximal canal cell, whose cytoplasmic processes interdigitate
      to form a typical weir. There are many internal leptotriches (cytoplasmic
      outgrowths into the lumen of the flame bulb), but no (or very few) external
      leptotriches. A septate junction, some surface lamellae, as well as numerous
      vacuoles, some of which open into the canal lumen, are found in the wall of the
      proximal canal. Lateral flames are present in the larger capillaries. Two
      excretory bladders, each with a nucleus and containing many excretory
      concrements, are located dorso-laterally. They open dorso-laterally through
      narrow ducts lined by a thick wall containing electron-dense and lucent vacuoles.
      Phylogenetic implications of the findings are discussed.

PMID- 9764922
TI  - Ultrastructure of spermiogenesis and the spermatozoon of Vampirolepis microstoma
      (Cestoda, Hymenolepididae), intestinal parasite of Rattus rattus.
AB  - Spermiogenesis in Vampirolepis microstoma begins with the formation of a nuclear
      cone and a differentiation zone. This is delimited at the front by arched
      membranes, bordered by cortical microtubules, and contains two parallel
      centrioles linked together at their bases by electron-dense, amorphous material.
      The nuclear cone elongates, becomes filiform, and migrates into the spermatid
      body. Later, one of the centrioles gives rise to a flagellum that grows at the
      same pace as the cortical microtubules. Subsequently, 6 crested bodies form and
      the old spermatid separates from the residual cytoplasm. The mature V. microstoma
      spermatozoon is filiform and lacks mitochondria. Its anterior end exhibits six
      crested bodies 100 to 200 nm thick of unequal lengths. The axoneme is of the
      9+"1" pattern. The cortical microtubules are spiralized and make an angle of
      about 20 to 30 degrees to the spermatozoon axis, except at their posterior
      extremity where they become parallel to this axis. The nucleus is an electron
      dense cord coiled in a spiral around the axoneme. The cytoplasm is slightly dense
      but contains many electron-dense granules in regions III, IV, and V of the
      spermatozoon. The presence of centrioles linked together at their bases by
      electron-dense material has never, to our knowledge, been reported in a
      Platyhelminth. Likewise, a nuclear migration, right from the beginning to the end
      of spermiogenesis, has never been described in a cestode. In addition, we observe
      for the first time the existence of six crested bodies in a cestode from a
      Mammal.

PMID- 9764923
TI  - Testicular microvascularization in the common tree shrew (Tupaia glis) as
      revealed by vascular corrosion cast/SEM and by TEM.
AB  - Testicular angioarchitecture in lower primates has not been established and the
      route of androgens from Leydig cells entering the systemic circulation is still a
      matter of controversy. In the present study, the common tree shrew (Tupaia glis)
      was used as the model for vascular corrosion cast/SEM and conventional TEM
      studies. With vascular corrosion cast/SEM, it was revealed that while coursing in
      the spermatic cord, the testicular artery convoluted and gave off branches to
      supply the epididymis, the coverings of the spermatic cord and the pampiniform
      plexus. Upon approaching the testis, it encircled the organ, then penetrated into
      the testicular parenchyma near the rostro-medial pole before further dividing
      into arterioles that gave rise to capillary plexuses looping around the
      seminiferous tubules. These capillaries converged into the intratesticular
      venules, then into larger venules on ventral and dorsal surfaces of the testis
      and finally into the collecting veins on medial and lateral borders of the
      testis. In addition, the capillaries in the central or medullary portion of the
      gland collected the blood into the medullary venules and central (medullary)
      vein, respectively. The collecting veins as well as central vein joined together
      before dividing into pampiniform plexus. With transmission electron microscopy,
      the capillaries in the testis were shown to be of the thick basement membrane and
      continuous type. The Leydig cells were found adjacent to lymphatic vessels among
      the seminiferous tubules. This structure is compatible with the idea that most of
      the androgens drain into the lymphatic vessels rather than into the capillaries.

PMID- 9764924
TI  - Immunohistochemical localization of surfactant apoproteins in usual interstitial
      pneumonia associated with pulmonary carcinoma.
AB  - Surfactant apoproteins A and B (SP-A and SP-B) are antigenic determinants of
      pulmonary surfactant complexes. The role and functional significance of these
      proteins are largely unknown and the pattern of expression is probably related to
      the functional maturation of type II pneumocytes. Differential expression of SP-A
      and SP-B was reported in the developing human lung but little is known of their
      expression in the chronic injury. We studied 5 surgical cases of usual
      interstitial pneumonia (UIP) associated with carcinoma to evaluate the expression
      of pulmonary surfactant apoproteins. These cases were immunohistochemically
      examined by the streptavidin-biotin complex method using monoclonal antibodies HS
      1 and HS-2 against pulmonary surfactant apoprotein A (SP-A) and B (SP-B),
      respectively. In UIP, SP-B was expressed strongly in type II pneumocytes and
      Clara cells but bronchiolar epithelium and metaplastic squamous cell lines in the
      honeycomb lesion were non-reactive. SP-A showed a similar pattern but much weaker
      reactivity when compared to that of SP-B. Type II pneumocytes in normal lung
      tissue exhibited weak immunoreactivity and no difference in the intensity of
      staining between SP-A and SP-B. Neither carcinomatous area nor metaplastic lining
      cells at honeycomb lesion show immunoreactivity to SP-A and SP-B. These results
      suggest that type II pneumocytes in the UIP are functionally immature in their
      expression of the apoprotein types and the metaplastic squamous cells or
      neoplastic transformed cells do not have molecular characteristics of type II
      pneumocytes.

PMID- 9764925
TI  - Development of a small-scale bioreactor for drug metabolism studies maintaining
      hepatospecific functions.
AB  - 1. The aim of the study was the development of a small-scale liver cell
      bioreactor maintaining tissue monoxygenase activity and hepatospecific activities
      over at least 2 weeks. 2. For characterization the antihypertensive drug urapidil
      was used as a model compound to study maintenance of metabolic activity. Tissue
      specific parameters assessed included urea and albumin secretion as well as
      cellular integrity. The problem of the use of serum in bioreactor cultures is
      addressed. 3. Bioreactor runs could be performed in serum- and lactate-free
      cultures with a joint recovery of oxidative biotransformation capacity for
      urapidil as well as tissue-specific markers. LDH release was reduced with older
      cultures. Fibronectin was shown as a contributing factor for cell attachment. 4.
      In the present study the design and function of a modular, small-scale-type
      bioartificial liver cell culture model is thus described lending itself for drug
      metabolism studies but maintaining also typical hepatospecific properties.

PMID- 9764926
TI  - Induction of pulmonary CYP1A1 by nicotine.
AB  - 1. We have examined the catalytic activities (7-ethoxyresorufin O-deethylase
      [EROD] and 7-methoxyresorufin O-demethylase [MROD]), protein levels (Western blot
      analysis) and mRNA levels (Northern blot analysis) of cytochrome P4501A (CYP1A1
      and CYP1A2) in the lung, liver and kidney following a single 2.5 mg/kg (15.4
      micromol/kg) subcutaneous dose of nicotine to the female Sprague-Dawley rat. 2.
      Only in lung microsomes was EROD activity significantly induced by nicotine
      treatment. The activity increased 4.4-fold at 6 h after treatment relative to
      controls, peaked at 12 h at 14.7-fold the control activity and returned to near
      control level at 24 h. 3. In parallel with EROD activity, CYP1A1 immunoreactive
      protein abundance was altered significantly by nicotine treatment only in the
      lung, peaking at 12 h and decreasing towards control levels thereafter. 4.
      Following subcutaneous nicotine treatment, CYP1A1 mRNA was detectable in the lung
      at 6 and 12 h but not at 24 h, was slightly elevated in the kidney at 12 h and
      was detectable in the liver only at the 12-h point. CYP1A2 immunoreactive protein
      and its mRNA were detectable only in the liver, and their levels were not
      affected significantly by nicotine pretreatment. 5. Nicotine affected the binding
      of Hepa 1c1c7 cytosolic protein to a CYP1A1 xenobiotic response element in a gel
      mobility shift assay, suggesting involvement of the aryl hydrocarbon receptor and
      transcriptional activation in CYP1A1 induction by the chemical. 6. Inhaled
      nicotine also induced pulmonary EROD activity, and the induction by either
      inhaled or injected nicotine was more pronounced in the male than in the female
      rat. 7. The findings show that nicotine is a potent, rapid but transient inducer
      of CYP1A1 in the rat lung and suggest that the alkaloid is a likely contributor
      to CYP1A1 induction by cigarette smoke.

PMID- 9764927
TI  - Effects of propofol on human hepatic microsomal cytochrome P450 activities.
AB  - 1. The potential of propofol to inhibit the activity of major human cytochrome
      P450 enzymes has been examined in vitro using human liver microsomes. Propofol
      produced inhibition of CYP1A2 (phenacetin O-deethylation), CYP2C9 (tolbutamide 4'
      hydroxylation), CYP2D6 (dextromethorphan O-demethylation) and CYP3A4
      (testosterone 6beta-hydroxylation) activities with IC50 = 40, 49, 213 and 32
      microM respectively. Ki for propofol against all of these enzymes with the
      exception of CYP2D6, where propofol showed little inhibitory activity, was 30, 30
      and 19 microM respectively for CYPs 1A2, 2C9 and 3A4. 2. Furafylline,
      sulphaphenazole, quinidine and ketoconazole, known selective inhibitors of CYPs
      1A2, 2C9, 2D6 and 3A4 respectively, were much more potent than propofol having
      IC50 = 0.8, 0.5, 0.2 and 0.1 microM; furafylline and sulphaphenazole yielded Ki =
      0.6 and 0.7 microM respectively. 3. The therapeutic blood concentration of
      propofol (20 microM; 3-4 microg/ml) together with the in vitro Ki estimates for
      each of the major human P450 enzymes have been used to estimate the extent of
      cytochrome P450 inhibition, which may be produced in vivo by propofol. This in
      vitro-in vivo extrapolation indicates that the degree of inhibition of CYP1A2,
      2C9 and 3A4 activity which could theoretically be produced in vivo by propofol is
      relatively low (40-51%); this is considered unlikely to have any pronounced
      clinical significance. 4. Although propofol has now been used in > 190 million
      people since its launch in 1986, there are only single reports of possible drug
      interactions between propofol and either alfentanil or warfarin. Consequently, it
      is difficult to conclude from either the published literature or the ZENECA
      safety database whether there is any evidence to indicate that propofol produces
      clinically significant drug interactions through inhibition of cytochrome P450
      related drug metabolism.

PMID- 9764928
TI  - Hydrogen atom abstraction of 3,5-disubstituted analogues of paracetamol by
      horseradish peroxidase and cytochrome P450.
AB  - 1. The formation of free radicals during enzyme catalysed oxidation of eight 3,5
      disubstituted analogues of paracetamol (PAR) has been studied. A simple
      peroxidase system as well as cytochrome P450-containing systems were used.
      Radicals were detected by electron spin resonance (ESR) on incubation of PAR and
      3,5-diCH3-, 3,5-diC2H5-, 3,5-ditC4H9-, 3,5-diOCH3-, 3,5-diSCH3-, 3,5-diF-, 3,5
      diCl- and 3,5-diBr-substituted analogues of PAR with horseradish peroxidase in
      the presence of hydrogen peroxide (H2O2). Initial analysis of the observed ESR
      spectra revealed all radical species to be phenoxy radicals, based on the absence
      of dominant nitrogen hyperfine splittings. No radicals were detected in rat liver
      cytochrome P450-containing microsomal or reconstituted systems. 2. To rationalize
      the observed ESR spectra, hydrogen atom abstraction of PAR and four of the 3,5
      disubstituted analogues (3,5-diCH3-, 3,5-diOCH3-, 3,5-diF- and 3,5-diCl-PAR) was
      calculated using ab initio calculations, and a singlet oxygen atom was used as
      the oxidizing species. The calculations indicated that for all compounds studied
      an initial hydrogen atom abstraction from the phenolic hydroxyl group is favoured
      by approximately 125 kJ/mol over an initial hydrogen atom abstraction from the
      acetylamino nitrogen atom, and that after hydrogen abstraction from the phenolic
      hydroxyl group, the unpaired electron remains predominantly localised at the
      phenoxy oxygen atom (+/-85%). 3. The experimental finding of phenoxy radicals in
      horseradish peroxidase/H2O2 incubations paralleled these theoretical findings.
      The failure to detect experimentally phenoxy radicals in cytochrome P450
      catalysed oxidation of any of the eight 3,5-disubstituted PAR analogues is more
      likely due to the reducing effects that agents like NADPH and protein thiol
      groups have on phenoxy radicals rather than on the physical instability of the
      respective substrate radicals.

PMID- 9764929
TI  - Structural determination of metabolites of S-1153, a new, potent, non-nucleoside,
      anti-HIV agent in rat liver microsomes.
AB  - 1. S-1153, a non-nucleoside agent that is under development in the USA as a new
      anti-HIV agent, has potent antiviral activity based on the inhibition of reverse
      transcriptase. 2. S-1153 was incubated with rat liver microsomes and NADPH, and
      seven metabolites were formed. The main metabolites were identified as the S
      oxide, N-oxide and sulphone of S-1153. 3. Two other minor metabolites were
      assumed to be S-1153 hydroxylated on the isopropyl moiety. 4. Our findings
      confirmed the existence of at least three oxidative metabolic pathways of S-1153.

PMID- 9764930
TI  - Pharmacokinetic properties and oral bioavailabilities of difloxacin in pig and
      chicken.
AB  - 1. Pharmacokinetic properties of difloxacin have been studied in pig and chicken
      after intravenous and oral administration. 2. The serum concentrations of
      difloxacin in pig and chicken after intravenous administration were best
      described by a two-compartment open model, giving distribution half-lives of 0.50
      and 0.66 h and elimination half-lives of 7.92 and 4.10 h for pig and chicken
      respectively. The steady-state distribution volumes were 1.70 and 3.06 l/kg for
      pig and chicken respectively. 3. After oral administration of 5 mg/kg to pig and
      chicken, the serum concentrations reached maximal levels of 3.61 and 0.96
      microg/ml respectively at 1.25 and 1.40 h. The elimination half-lives were 11.8
      and 7.35 h for pig and chicken respectively. 4. The bioavailabilities of
      difloxacin were calculated as 93.7 (pig) and 86.9% (chicken).

PMID- 9764932
TI  - Type-specific serological testing for herpes simplex infection.

PMID- 9764931
TI  - In vitro toxicity of zamifenacin (UK-76,654) and metabolites in primary
      hepatocyte cultures.
AB  - 1. We compared the sensitivities of primary hepatocytes from rat, dog and monkey
      to zamifenacin and two major metabolites, the methylenedioxy ring-opened
      catechol, UK-80,178 and its methylated product, UK-82,201. Toxicity was
      determined both via neutral red uptake and enzyme leakage data. 2. Canine
      hepatocytes were most sensitive to the cytotoxic effects of zamifenacin during 24
      h exposure. Significant decreases in medium concentrations of zamifenacin in the
      presence of primary hepatocytes verified cellular uptake during the initial 2-h
      incubation. All three cell types were much more sensitive to UK-82,201 than to
      the catechol metabolite or parent drug. 3. The rapid onset of cytotoxicity
      indicated by elevations of alanine aminotransferase (ALT), aspartate
      aminotransferase (AST) and other markers in the medium after UK-82,201 exposure,
      the delayed but substantial cytotoxic response to the parent drug which was
      suggestive of biotransformation to a reactive moiety, in vivo and in vitro drug
      metabolism results and subacute toxicology data suggest that dog may more
      effectively transform zamifenacin into UK-82,201, which is relatively
      hepatotoxic. 4. Because the catechol was generally less toxic than the O
      methylated product, species that eliminate zamifenacin primarily as the catechol
      or its conjugate may be less affected by the potential hepatotoxicity of the
      methylated product. Our studies show that dog is the most sensitive species due
      to metabolism of the common catechol metabolite. The low incidence of potential
      hepatotoxicity in the clinic points to rare but important differences in the
      metabolism of Zamifencin. We conclude that the findings in dog were not
      predictive of subsequent effects in man.

PMID- 9764933
TI  - Sexually transmitted organisms in children and child sexual abuse.

PMID- 9764934
TI  - Financing HIV service provision in England: estimated impact of the cost of
      antiretroviral combination therapy.
AB  - The objective of this study was to provide population-based estimates on the cost
      of HIV service provision in England and the use of dual or triple antiretroviral
      combination therapy. Contemporary cost estimates of treating HIV-infected
      individuals by clinical stage of HIV infection (indexed to 1995/96 prices) were
      linked to the number of diagnosed HIV-infected individuals using statutory
      medical services in England during 1996. Two cost measures were used: the first
      one was based on average hospital prices derived from a number of English HIV
      units. These results were compared with those estimated using standard unit costs
      obtained through specific costing studies performed at a national HIV referral
      centre. Overall annual expenditure on HIV service provision was estimated for
      different treatment scenarios as was expenditure by clinical stage of HIV
      infection. Using hospital prices, in 1996 the total annual cost estimate for HIV
      service provision amounted to pound sterling 131 m (range pound sterling 83 m to
      pound sterling 233 m), or pound sterling 150 m (95% CI pound sterling 126 m to
      pound sterling 173 m) using standard costs, if all patients with HIV disease were
      treated with AZT monotherapy. For all eligible patients to be treated with dual
      therapy, cost estimates amounted to pound sterling 161 m (range pound sterling
      126 m to pound sterling 173 m) per year using hospital prices or pound sterling
      180 m (95% CI pound sterling 156 m to pound sterling 203 m) when using standard
      cost estimates, while for triple therapy annual estimated expenditure amounted to
      pound sterling 204 m per year (range pound sterling 157 m to pound sterling 306
      m) when using hospital prices or pound sterling 223 m (95% CI pound sterling 199
      m to pound sterling 246 m) using standard costs. Increasingly costs will be more
      evenly distributed across the 3 stages of HIV infection, with a greater
      proportion of costs generated by HIV-infected individuals before the onset of
      AIDS. Using non-standardized hospital prices may systematically underestimate the
      real cost of service provision. Monitoring prospectively the use, cost and
      outcome of HIV service provision in a standardized format will provide
      information on the actual cost impact over the next 2-3 years of combination
      therapy compared with the scenario-based estimates produced in this paper.

PMID- 9764935
TI  - Bronchopulmonary Kaposi's sarcoma in 106 HIV-1 infected patients.
AB  - The objectives of this study were to describe the clinical and radiological
      features at presentation, and the natural history of HIV-related bronchopulmonary
      Kaposi's sarcoma. A retrospective review of medical records and chest radiographs
      was performed in 106 HIV-infected homosexual men with bronchopulmonary Kaposi's
      sarcoma diagnosed at bronchoscopy between September 1988 and November 1994. The
      majority of patients had evidence of advanced HIV disease at diagnosis (median
      CD4 cell count was 15 x 10(6)/l, range 0-288), and 93% had had a diagnosis of
      cutaneous Kaposi's sarcoma for a median duration of 11 months prior to diagnosis
      of their bronchopulmonary disease. The most frequent symptoms at presentation
      were cough (92%), dyspnoea (69%), pleuritic pain (20%), haemoptysis (13%) and
      wheezing (10%). The most common radiological finding in 73% of our series was of
      poorly defined and confluent opacities, with predominant middle and lower zone
      involvement. Median survival was 4 months (range 0-37 months) from diagnosis and
      9 months (range 1-25) from the onset of symptoms. Treatment with either
      chemotherapy or radiotherapy was associated with a significantly reduced risk of
      death (hazards ratio (HR)=0.48, 95% CI=0.26-0.87). Factors associated with a poor
      survival, after adjustment for treatment effect were older age (HR=1.79, 95%
      CI=1.22-2.84) for each 10-year increase in age; a history of pleuritic pain
      (HR=2.97, 95% CI=1.39-6.32); presence of pleural effusion on X-ray (HR=2.01, 95%
      CI=1.13-3.59) and a prior diagnosis of cutaneous Kaposi's sarcoma (HR=1.8, 95%
      CI=1.00, 3.24). Bronchopulmonary Kaposi's sarcoma occurs mainly in patients with
      advanced HIV disease and a prior history of cutaneous disease. Survival is poor,
      and adverse prognostic factors include older age at diagnosis and the presence of
      pleural disease.

PMID- 9764936
TI  - Vulvovaginal candidiasis in female sex workers.
AB  - Vulvovaginal candidiasis is a frequent inflammatory process in women but it has
      not been widely studied in female sex workers (FSWs). To estimate the frequency
      of Candida species infection in FSWs and to identify related risk factors and
      clinical findings, we carried out a retrospective study of 1923 FSWs over 11
      years. We also performed a prospective study of 163 consecutive FSWs with a
      history of candidiasis during a 4-year period. Candida species were isolated in
      1967 samples (18.5% of the total). Candida albicans (89.3%) was the most frequent
      species, followed by Candida glabrata (2.7%), Candida parapsilosis (1.2%) and
      Saccharomyces cerevisiae (0.4%). In the prospective study of 163 patients, we
      found vaginal discharge in 76.1% of cases, soreness in 52.1% and vulval pruritus
      in 32.5%. We identified 12 patients (7.4%) with recurrent vulvovaginal
      candidiasis. No statistical difference was found between recurrent vulvovaginitis
      and the use of oral contraceptives, oral sex, tight-fitting clothing and
      synthetic underwear. FSWs have the same prevalence of candidiasis as other groups
      of women described in published literature. The proportion of albicans and non
      albicans species does not differ between women with recurrent and non-recurrent
      vulvovaginal candidiasis (VVC).

PMID- 9764937
TI  - Clinical and in situ cellular responses to Haemophilus ducreyi in the presence or
      absence of HIV infection.
AB  - We aimed to determine if the clinical and histological features of chancroid are
      altered by HIV infection. Male patients presenting to the Nairobi special
      treatment clinic with a clinical diagnosis of chancroid were eligible for the
      study. A detailed history, physical examination, swabs for Haemophilus ducreyi
      culture and blood for HIV serology, syphilis serology and CD4 counts were
      obtained from all patients. Punch biopsies from an ulcer were obtained from 10
      patients and either fixed in 10% formalin or snap frozen in Optimum Cutting
      Temperature (OCT) medium compound at -70 degrees C. Patients were treated with
      erythromycin and followed for 3 weeks. Chi-square and Student's t-test were used
      to determine if the clinical and laboratory features of chancroid differed
      between HIV-seropositive and seronegative individuals. Cox regression survival
      analysis was used to determine if HIV infection altered cure rates of chancroid
      at 21 days. Immunohistochemical staining was performed using lymphocytic and
      macrophage markers and tissue sections were analysed by 2 pathologists in a
      blinded manner. Between February and November 1994, 109 HIV-seropositive and 211
      HIV-seronegative individuals were enrolled in the study. HIV patients had ulcers
      of longer duration than HIV-seronegative patients (P=0.03). Although cure rates
      were similar at 3 weeks, HIV patients had lower cure rates at 1 week (23% v 54%,
      P=0.002). A dense interstitial and perivascular inflammatory infiltrate extending
      from the reticular to deep dermis was present in all biopsies. This consisted of
      equal amounts of CD4 and CD8 T-lymphocytes as well as macrophages. The
      histological and immunohistochemical picture was identical for HIV-positive and
      negative patients. HIV infection slows the healing rates of chancroid ulcers
      despite appropriate antibiotic therapy. This clinical difference cannot be
      attributed to an altered histopathological response to HIV infection. Additional
      studies are needed to elucidate the mechanisms responsible for this finding.

PMID- 9764938
TI  - Efficacy of surgical and/or podophyllotoxin treatment against flat acetowhite
      penile human papillomavirus associated lesions.
AB  - In order to investigate the efficacy of treatment modalities favoured by us
      against flat acetowhite penile human papillomavirus (HPV)-induced lesions, we
      studied retrospectively standardized medical records of 81 men who had been
      treated for this condition. The patients were treated surgically with diathermy
      (n=32) or with a combination of both chemical (topical application of
      podophyllotoxin) and surgical treatment (n=49). The mean number of clinic visits
      was 9.1 (range 1-19), during a follow-up time of mean 30.9 (range 1-104) months
      for 78 of the men, 3 of them only visited the clinic once. The mean time for cure
      was 19.9 (range 0-103) months. Only 12 (15%) patients were healed after one
      single treatment session, while as many as 50 (62%) required > 4 sessions. The
      mean number of surgical treatment sessions required for cure differed
      significantly (P=0.0006) between the previously treated patients who needed a
      mean of 5.6 treatment sessions, compared to the previously untreated men who
      required surgery a mean of 3.4 times for cure.

PMID- 9764939
TI  - Emergency unit care of sexually transmitted infections.
AB  - The aim of the study was to assess provisions for management of sexually
      transmitted infections (STIs), emergency contraception and pregnancy test in UK
      emergency departments. Postal questionnaires were sent to all consultant-led
      emergency departments in the UK in January 1996. The response rate was 64%. Most
      departments made direct referrals to genitourinary medicine (GUM) clinics and
      most had access to appropriate clinics. While 55% had facilities for diagnosis of
      at least one of the 3 common STIs (Chlamydia trachomatis, Neisseria gonorrhoeae
      and herpes simplex), only 6.25% had facilities for all 3. A minority of units
      provided training in the management of STIs. Emergency physicians should be
      trained in the early management of STIs and a coordinated working relationship
      should be developed between emergency and GUM departments to provide optimal
      sexual health care.

PMID- 9764940
TI  - Cytomegalovirus pp65 antigenaemia as an indicator of end-organ disease in AIDS.
AB  - We aim to assess the usefulness of the cytomegalovirus (CMV) pp65 antigenaemia
      test, also called the CMV direct antigen test (DAT), in the management of
      patients with advanced human immunodeficiency virus (HIV) infection; we studied
      all patients who had pp65 assays between 8 September 1995 and 30 August 1996.
      Twenty-three patients had 31 tests. The mean CD4 cell count was 20/mm3. The tests
      were negative in 16 patients, of whom 12 have not developed CMV end-organ disease
      after a mean follow up of 114 days (range 14-269 days), whilst the remaining 4
      patients had previously treated CMV disease. Eleven patients had positive tests:
      4 had active CMV disease, 2 subsequently developed CMV retinitis, 2 died within a
      fortnight of multi-drug resistant tuberculosis (MDR-TB), one was lost to follow
      up and 2 have remained disease-free. This test has a positive predictive value of
      43% and a negative predictive value of 94%, Fisher's exact test P=0.03. The pp65
      antigenaemia assay can be performed in a standard virology laboratory avoiding
      the problems associated with polymerase chain reaction (PCR), a result is
      available within 5 h, and it is semi-quantifiable. However, a large prospective
      study is required to determine the comparative value and roles of the pp65
      antigenaemia assay and DNA PCR in the management of CMV disease, especially with
      regard to the use of primary prophylaxis and pre-emptive therapy.

PMID- 9764941
TI  - HIV infection and asymptomatic sexually transmitted infections in a rural South
      African community.
AB  - The objective was to determine the prevalence of HIV and other sexually
      transmitted infections (STIs) in a rural community. A population-based survey of
      adults in 110 homesteads was conducted in 1995. A questionnaire on demographics,
      sexual practices and history of STDs was administered. Neisseria gonorrhoeae and
      Chlamydia trachomatis infections were detected using ligase chain reaction (LCR)
      assay of urine. The seroprevalence of syphilis rapid plasma reagin (RPR) and
      Treponema pallidum haemagglutination assay (TPHA) and HIV infection (ELISA) was
      determined. Among 259 subjects the prevalence of HIV was 10.5%, N. gonorrhoeae
      4.5%, C. trachomatis 6.1% and active syphilis 8.8%. All infections were
      asymptomatic. Forty per cent of sexually active men had more than one concurrent
      sexual partner. Only 14% of subjects had ever used condoms. The STI epidemic is
      being promoted by high levels of asymptomatic infections, high partner
      concurrency and low condom use.

PMID- 9764943
TI  - Renal calculi developing de novo in a patient taking saquinavir.

PMID- 9764942
TI  - The availability and cost of antibiotics for treating PID in the Central Region
      of Ghana and implications for compliance with national treatment guidelines.
AB  - The availability and cost of antibiotics for treating pelvic inflammatory disease
      (PID) were assessed in 17 drug-dispensing outlets in 5 districts of the Central
      Region, Ghana. The outlets included the dispensaries of 2 regional and 4 district
      hospitals, 4 privately-owned pharmacies and 7 chemical seller shops. The most
      common antibiotics available, including co-trimoxazole, metronidazole,
      benzylpenicillin, amoxycillin, chloramphenicol and gentamicin, were also the
      lowest-priced drugs. Conversely, the most expensive antibiotics including
      ceftriaxone, ciprofloxacin, cefuroxime and spectinomycin, were also the least
      commonly available. Recommended anti-gonococcal antibiotics (ciprofloxacin,
      ceftriaxone) may not be prescribed if they are not available in the districts.

PMID- 9764945
TI  - Cervical smear: is screening of teenagers justified?

PMID- 9764944
TI  - Redefining AIDS: case exemplified by Penicillium marneffei infection in HIV
      infected people in Hong Kong.

PMID- 9764946
TI  - Study Site Coordinator/Research Nurse.

PMID- 9764947
TI  - Epidemiology, demographics, and genetics of sarcoidosis.
AB  - Epidemiological knowledge of sarcoidosis is based mainly on studies performed
      more than 30 years ago. These early case-control studies produced some
      interesting risk factor-disease associations, but a clear causative mechanism in
      sarcoidosis remains unknown. Studies in military and veteran populations showed a
      clear preponderance of sarcoidosis in African Americans compared with Caucasians.
      Our recent sarcoidosis incidence study in a racially heterogeneous population
      found African Americans at three- to fourfold greater risk, which was less than
      the 10 to 17 times greater risk previously reported. Females are consistently
      found at greater risk than males, although the relative risk difference generally
      does not exceed two. The striking racial differences and numerous reports of
      familial clustering suggest genetic susceptibility. We have found that familial
      sarcoidosis is almost three times more common in African-American (17%) than
      Caucasian cases (6%). Future genetic studies can benefit from the extensive
      catalog of candidate genes that is emerging from the human genome project. The
      epidemiological evidence to date strongly suggests that studies seeking causes
      for sarcoidosis need to consider both environmental and genetic risk factors to
      be successful because the two likely interact with each other to produce disease.

PMID- 9764948
TI  - Involvement of T cells and alterations in T cell receptors in sarcoidosis.
AB  - Sarcoidosis is recognized to be a multisystem granulomatous disease characterized
      by activated, cytokine-producing T cells and macrophages at sites of
      inflammation. The purpose of this article is to review new evidence concerning
      the role of T cells in sarcoidosis. Recent work on the molecular structure and
      repertoire of T cell receptor genes in sarcoidosis provide direct evidence that
      sarcoidosis is characterized by selective expansions of oligoclonal populations
      of T cells at sites of inflammation, consistent with local antigen-driven immune
      responses. In addition, data on cytokine production in sarcoidosis indicate that
      tissue inflammation is dominated by expression of type 1 (T helper 1) cytokines
      such as interferon-gamma and interleukin-12 that, in keeping with experimental
      models of granulomatous diseases, likely orchestrate the granulomatous response.
      These studies offer new insight into the molecular mechanisms of granuloma
      formation in sarcoidosis and provide a framework for developing new therapeutic
      strategies for the treatment of this disease.

PMID- 9764949
TI  - Cytokines in sarcoidosis.
AB  - Although the cause of sarcoidosis is still unknown, the combination of the
      characteristic morphologic aspect and the immunohistologic pattern of the sarcoid
      granulomatous lesions suggest that they are the result of an antigen-driven
      process. In particular, sarcoid granuloma is considered to be the consequence of
      an exaggerated immunological response against an undefined antigen which has
      persisted at the sites of disease involvement. Taking advantage of the
      availability of pure recombinant cytokines and molecular probes for cytokines and
      their receptors, in the last few years it has been possible to keenly study the
      involvement of several cytokines in the pathologic changes associated with
      sarcoidosis. The purpose of this review is to summarize the interactions between
      cytokines and their receptors which define regulatory networks ultimately
      contributing to the sarcoid granuloma formation at sites of disease activity.
      After a concise overview of the main cytokines involved in the sarcoid
      inflammatory response, we will briefly discuss the biological effects of Th1 and
      Th2 cytokines in sarcoid lung and then concentrate on the importance of the local
      production of those molecules whose release has been recently shown within the
      lung of patients with sarcoidosis, such as interleukin-12, interleukin-15, and
      chemokines. Furthermore, we will focus the discussion on the cytokines which,
      pivotal to the activation of the host defenses, may contribute to lung damage and
      the consequent lung fibrosis. The final section of this article reviews the lung
      release of cytokines in the context of recent hypotheses claiming microbial
      pathogens as putative causative agents of sarcoidosis.

PMID- 9764951
TI  - Kveim antigen: what does it tell us about causation of sarcoidosis?
AB  - This article explores the role of the Kveim-Siltzbach (KS) test in finding the
      cause of sarcoidosis. Experimental granulomas are formed by a T-cell mediated
      immunologic response to particulate agents which resist degradation and persist
      in tissues for prolonged periods. There is no animal model for human sarcoidosis.
      However, the KS test is an in vivo model of sarcoidosis. KS homogenates incite a
      tissue response in patients with sarcoidosis histologically identical to disease
      caused granulomas. The suspensions are particulate and maintain activity when
      exposed to a variety of chemical and physical stresses. Studies of the monocyte
      and T-cell host response confirm that KS reagent provokes a sarcoidosis-like
      antigen driven granuloma. KS suspensions contain an antigen(s) that incite a
      granuloma identical with that occurring in sarcoidosis. Identification of the
      active principle in KS suspensions should aid in the search for the cause of
      sarcoidosis.

PMID- 9764950
TI  - The role of mycobacteria in the pathogenesis of sarcoidosis.
AB  - The pathogenesis of sarcoidosis has intrigued clinicians since the first
      descriptions of the disease, and a number of causes have been proposed. Among the
      candidate agents, the possible role of mycobacterial infection in the
      pathogenesis of sarcoidosis has attracted by far the most attention. The purpose
      of this review is to summarize current evidence concerning the role of
      mycobacterial infection in sarcoidosis. First, the similarities in clinical and
      histological features of tuberculosis and sarcoidosis that have raised suspicion
      that mycobacterial infection could be involved in the pathogenesis of sarcoidosis
      are discussed. In addition, experimental evidence for and against a role of
      mycobacterial infection is summarized, including recent attempts to detect
      mycobacterial DNA in clinical samples from patients with sarcoidosis by
      polymerase chain reaction.

PMID- 9764952
TI  - Metals that cause sarcoidosis.
AB  - Inhalation of metal dust or fume can cause granulomatous lung disease that mimics
      sarcoidosis. Particular metals that possess antigenic properties which promote
      granuloma formation include aluminum, barium, beryllium, cobalt, copper, gold,
      rare earths (lanthanides), titanium, and zirconium. The occupational and
      environmental exposure history holds the key to linking such metals with
      seemingly idiopathic disease. We propose clinicians use a systematic approach to
      investigating the occupational and environmental history and immunologic
      responses of patients with sarcoidosis, in order to discriminate metal-induced
      granulomatosis from sarcoidosis.

PMID- 9764953
TI  - Animal models of granulomatous inflammation.
AB  - The pathogenesis of granulomatous inflammation is often characterized as an
      intense inflammatory response with accompanying fibroproliferation and deposition
      of extracellular matrix. Many of these chronic disorders share a number of common
      characteristics, including an enigmatic cause, unknown mechanisms of initiation
      and maintenance, and often untreatable end-stage fibrosis. Granulomatous
      inflammation can occur in a variety of diseases, such as tuberculosis,
      sarcoidosis, berylliosis, and Wegner's granulomatosis. Unfortunately, these
      diseases are often associated with substantial morbidity and mortality, as
      therapeutic options may not be entirely efficacious. The lack of a clear
      treatment strategy may underscore the limited scientific understanding of these
      disorders. Thus, experimental models of granulomatous inflammation, which mimic
      some of the specific characteristics of these responses, will be useful in
      delineating the mechanisms of granuloma development. In addition, these models
      may aid in the design of useful therapies for the treatment of these inflammatory
      diseases.

PMID- 9764954
TI  - Extrapulmonary sarcoidosis.
AB  - The clinical manifestations of sarcoidosis are extremely heterogeneous and
      overlap with a wide gamut of infectious and noninfectious granulomatous
      disorders. Prognosis of sarcoidosis is highly variable. Spontaneous remissions
      occur in nearly two thirds of patients, but chronic, progressive disease may
      result in severe sequelae. Fatalities occur in 1% to 4% of patients. Pulmonary
      manifestations typically dominate, but any organ can be affected. Skin, eye, and
      peripheral lymph nodes are each involved in 20% to 30% of patients. Clinically
      significant involvement of spleen, liver, bone, heart, kidney, or central nervous
      system occurs in 2% to 6% of patients. Asymptomatic involvement of these organs
      is far more common. We review the salient extrapulmonary features of sarcoidosis,
      and compare and contrast specific features that may mimic other etiologies.

PMID- 9764955
TI  - Sarcoidosis: is therapy effective?
AB  - Treatment of sarcoidosis is controversial. The clinical expression and natural
      history of sarcoidosis is variable, and spontaneous remissions occur in up to 60%
      of patients. The decision to treat (or withhold treatment) is often difficult.
      Corticosteroids, immunosuppressive/cytotoxic, and immunomodulatory agents are
      used to treat chronic or progressive sarcoidosis, but prospective, randomized
      trials assessing efficacy of these agents are lacking. Toxicities associated with
      therapy may be substantial, particularly when high dosages are used. We review
      the pharmacologic agents used to treat sarcoidosis, toxicities associated with
      treatment, and appropriate use and monitoring of these therapeutic modalities.

PMID- 9764956
TI  - Radiographic findings in semi-invasive pulmonary aspergillosis.

PMID- 9764957
TI  - Therapeutic drug monitoring--antiepileptic drugs.
AB  - AIMS: To provide a brief critical review of the basis and contemporary practice
      of monitoring the concentrations of antiepileptic drugs in biological fluids.
      METHODS: The review is based on literature data and observations from clinical
      practice. RESULTS: As experience has accumulated, monitoring of antiepileptic
      drug concentrations has come to be applied mainly to certain of the drugs when
      present in whole plasma. For these drugs there is a reasonably established
      relationship between drug concentrations and biological effects, but attention
      still needs to be paid to issues such as the timing of the measurements in
      relation to drug intake, the presence or absence of steady-state conditions, the
      presence in plasma of active metabolites and possible nonlinear pharmacokinetics
      of particular agents e.g. phenytoin. CONCLUSIONS: Plasma antiepileptic drug
      concentration monitoring is coming to be used in a more thoughtful and critical
      manner. Lack of adequate knowledge of matters such as the relationship between
      the plasma concentrations and antiepileptic and toxic effects of the drugs, not
      only the newer, but also the longer established ones, in particular clinical
      situations, remains more important than deficiencies in analytical methodology in
      limiting the clinical usefulness of antiepileptic drug concentration monitoring.

PMID- 9764958
TI  - Prescription-event monitoring--recent progress and future horizons.

PMID- 9764959
TI  - Midazolam pharmacokinetics following intravenous and buccal administration.
AB  - AIMS: Midazolam has good anxiolytic qualities and is a well established
      premedication agent before anaesthesia or short surgical procedures. The
      objective of the present study was to determine pharmacokinetic data from
      individual plasma concentration profiles obtained following intravenous and
      buccal administration of midazolam. METHODS: Eight young healthy volunteers
      received single doses of 5 mg midazolam i.v. and after a period of 1 week
      buccally in a cross over manner. Blood samples were obtained up to 480 min. The
      measurement of plasma midazolam concentrations was by gas-chromatography.
      RESULTS: The maximum plasma concentration was 55.9 ng ml(-1) (range 35.6-77.9 ng
      ml(-1)) at 30 min (range 15-90 min) following buccal administration. AUC was
      calculated to be 15016 ng ml(-1) min (s.d. 3778 ng ml(-1) min) following i.v. and
      11191 ng ml(-1) min (s.d. 1777 ng ml(-1) min) following buccal midazolam. This
      gave a mean midazolam bioavailability of 74.5%. CONCLUSIONS: The pharmacokinetic
      data presented in this study demonstrate a high bioavailability and reliable
      plasma concentrations following buccal midazolam. The clinical benefit of buccal
      midazolam may be in particular patient controlled premedication or sedation in
      adults.

PMID- 9764960
TI  - The gastrointestinal passage and release of beclomethasone dipropionate from oral
      delivery systems in ileostomy volunteers.
AB  - AIMS: To study the delivery of 15 mg beclomethasone 17,21-dipropionate (BDP) to
      the distal part of the small bowel for three oral sustained-release formulations
      (I-III) and a reference capsule in volunteer ileostomists, and to compare these
      findings with the in vitro dissolution profiles. METHODS: Two groups of nine
      ileostomy volunteers (aged 20-61 years), who were otherwise healthy, were
      enrolled in the study. The recovery of BDP and its metabolite beclomethasone 17
      monopropionate (B17P) in ileostomy effluent was investigated in a cross-over
      study after administration of formulations I or II or a reference capsule
      containing micronised BDP, and in a second open study after administration of
      formulation III. Radio-opaque granules were coadministered for evaluation of
      gastrointestinal passage. Ileostomy effluents were collected hourly for 10-12 h
      following drug intake. After marker beads had been counted on X-rays, ileostomy
      collections were analysed for BDP and its metabolites. Cumulative recovery, lag
      time and mean transit time were determined for drug and marker beads. RESULTS:
      Gastrointestinal passage characteristics were similar for all treatments. Total
      drug recovery was approximately three times higher for the sustained-release
      formulations than for the reference capsule. Recovery of B17P from stoma fluid
      samples was significantly lower for formulation III than for formulations I and
      II. CONCLUSIONS: The novel oral formulations delivered substantial amounts of
      steroid drug at the distal small bowel/proximal colon, which may warrant further
      studies to evaluate clinical applicability.

PMID- 9764961
TI  - Chloroquine modulation of specific metabolizing enzymes activities: investigation
      with selective five drug cocktail.
AB  - AIMS: The aim of this study was to investigate whether chloroquine can inhibit
      drug metabolism in humans, if such inhibition is general or selective for certain
      enzymes and evaluate the potential for and clinical significance of any drug-drug
      interactions when chloroquine is co-administered with other drugs. METHODS: The
      study was conducted in fourteen normal non-smoking healthy male volunteers using
      a cocktail of five drugs consisting of caffeine, mephenytoin, debrisoquine,
      chlorzoxazone and dapsone to assess activities of cytochromes P450 (CYP) 1A2,
      2C19, 2D6, 2E1 and 3A4 respectively. Dapsone was also used to assess N
      acetyltransferase activity. The activities were assessed at baseline, after one
      and seven daily doses (250 mg daily) of chloroquine and 7 and 14 days after
      stopping chloroquine dosing. RESULTS: Chloroquine caused a progressive and
      significant decrease in CYP2D6 activity as measured by debrisoquine metabolism
      from first to seventh dose and the activity returned to baseline gradually over
      14 days after stopping administration. There was no effect on the metabolism of
      any of the other probe drugs. CONCLUSIONS: Chloroquine has been shown to be
      capable of inhibiting the activity of CYP2D6 in vivo in humans. This effect is
      selective as activities of other enzymes investigated were not affected. The
      effect was modest but suggests a potential for drug-drug interactions when co
      administered with other drugs that are substrates for this enzyme. The clinical
      significance of such an interaction will depend on the therapeutic index of any
      drug involved.

PMID- 9764963
TI  - Population pharmacokinetics of gentamicin in patients with cancer.
AB  - AIMS: The purpose of this study was to describe the population pharmacokinetics
      of gentamicin in patients with cancer, to identify possible relationships between
      clinical covariates and population pharmacokinetic parameter estimates and to
      examine the relevance of existing dosage nomograms in light of the population
      model developed in these patients. METHODS: Data were collected prospectively
      from 210 patients with cancer and were analysed with package NONMEM. Data were
      split into two sets: a population data set and an evaluation set. Creatinine
      clearance was estimated using measured creatinine concentrations and using 'low'
      creatinines set to a minimum of 60 micromol l(-1), 70 micromol l(-1) or 88.4
      micromol l(-1) RESULTS: A two compartment model was fitted to the concentration
      time curve. Two best models were obtained, one that related clearance to
      estimated creatinine clearance (minimum creatinine value 60 micromol l(-1)) and
      the other that related clearance to age, creatinine concentration and body
      surface area. Volume of the central compartment was influenced by body surface
      area and albumin concentration. For both models 90% of measured concentrations
      lay within the 95% confidence interval of the simulated concentrations and the
      mean prediction errors were -7.2% and -6.6%, respectively. A final analysis
      performed in all patients identified the following relationship CL (1 h(-1))=0.88
      x (1 + 0.043 x creatinine clearance) and central volume of distribution V1
      (1)=8.59 x body surface area x (albumin/34)(-0.39). The mean population estimate
      of intercompartmental clearance (Q) was 1.301 h(-1) and peripheral volume of
      distribution (V2) was 9.801. Coefficient of variation was 18.5% on clearance and
      28.2% on Q. Residual error expressed as a standard deviation was 0.36 mg l(-1) at
      1.0 mg l(-1) and 1.32 mg l(-1) at 8.0 mg l(-1). The mean population estimate of
      clearance was 4.21 h(-1) and volume of distribution (Vss) was 24.61 (0.381 kg(
      1)). The mean population estimates of half-lives were 1.8 h and 8.0 h.
      CONCLUSIONS: In the context of published nomograms this analysis indicated that
      both the traditional approach and the new, 'once daily' approach should achieve
      satisfactory concentrations in cancer patients although serum concentration
      monitoring is required to confirm optimal dosing in individual patients.

PMID- 9764962
TI  - Caffeine based measures of CYP1A2 activity correlate with oral clearance of
      tacrine in patients with Alzheimer's disease.
AB  - AIMS: To study the potential utility of caffeine based probes of CYP1A2 enzyme
      activity in predicting the pharmokinetics of tacrine in patients with Alzheimer's
      disease. METHODS: The pharmokinetics of a single 40 mg oral dose of tacrine were
      measured in 19 patients with Alzheimer's disease. Each patient also received 2 mg
      kg(-1) [13C-3-methyl] caffeine orally and had breath and urine samples collected.
      RESULTS: Tacrine oral clearance (CL F(-1) kg(-1)), which varied 15-fold among the
      patients, correlated significantly with the 2 h total production of 13CO2 in
      breath (r=0.56, P=0.01), and with each of two commonly used urinary caffeine
      metabolite ratios: the 'paraxanthine/caffeine ratio' (1,7X + 1, 7U)/1,3,7X)
      (r=0.76, P=0.0002) and the 'caffeine metabolic ratio' (AFMU + 1X + 1U)/1,
      7U)(r=0.76, P=0.0001). CONCLUSIONS: These observations support a central role for
      CYP1A2 in the in vivo disposition of tacrine and the potential for drug
      interactions when tacrine treated patients receive known inducers or inhibitors
      of this enzyme. The magnitude of the correlations we observed, however, are
      probably not sufficient to be clinically useful in individualizing tacrine
      therapy.

PMID- 9764964
TI  - Paracetamol plasma and cerebrospinal fluid pharmacokinetics in children.
AB  - AIMS: Paracetamol has a central action for both antipyresis and analgesia.
      Maximum temperature decrease and peak analgesia are reported at 1-2 h after peak
      plasma paracetamol concentration. We wished to determine the relationship between
      plasma and cerebrospinal fluid (CSF) pharmacokinetics in children. METHODS:
      Concentration-time profiles in plasma and CSF after nasogastric paracetamol 40 mg
      kg(-1) were measured in nine children who had indwelling ventricular drains.
      Estimation of population pharmacokinetic parameters was made using both a
      standard two-stage population approach (MKMODEL) and a nonlinear mixed effect
      model (NONMEM). Results were standardized to a 70 kg person using an allometric
      power model. RESULTS: Both approaches gave similar estimates. NONMEM parameter
      estimates were clearance 10.21 h(-1) (CV 47%), volume of distribution 67.11 (CV
      58%) and absorption rate constant 0.77 h(-1) (CV 49%). Cerebrospinal fluid
      concentrations lagged behind those of plasma. The equilibration half time was
      0.72 h (CV 117%). The CSF/plasma partition coefficient was 1.18 (CV 8%).
      CONCLUSIONS: Higher concentrations in the CSF probably reflect the lower free
      water volume of plasma. The CSF equilibration half time suggests that CSF
      kinetics approximate more closely to the effect compartment than plasma, but
      further time is required for paracetamol to exert its effects. Effect site
      concentrations equilibrate slowly with plasma. Paracetamol should be given 1-2 h
      before anticipated pain or fever in children.

PMID- 9764965
TI  - A comparison of the cardiovascular effects of levobupivacaine and rac-bupivacaine
      following intravenous administration to healthy volunteers.
AB  - AIMS: The aim of this study was to compare the cardiovascular effects of
      levobupivacaine with those of rac-bupivacaine following i.v. administration to 14
      healthy male volunteers. METHODS: Drugs were infused (at 10 mg min(-1)) using a
      randomized, double-blind, complete crossover procedure with a washout period of
      at least 1 week. The administration of drug was discontinued on the appearance of
      defined CNS symptoms or when a total of 150 mg had been given. Parameters
      measured were arterial blood pressure, heart rate, ECG, ejection fraction,
      acceleration index, stroke index and cardiac index. RESULTS: The mean doses
      administered were 56.1 mg and 47.9 mg for levobupivacaine and rac-bupivacaine
      respectively and the maximum mean plasma concentrations were 2.62 and 2.25 microg
      ml(-1) respectively. Despite the dose and plasma concentrations being comparable,
      levobupivacaine produced a statistically significant smaller reduction in mean
      stroke index (-5.14 vs -11.86 ml m(-2), P=0.001), acceleration index (-0.09 vs 
      0.20 s(-2), P=0.011) and the ejection fraction (-2.50 vs -4.29%, P=0.024). Both
      levobupivacaine (non significant) and rac-bupivacaine (significant) produced
      small increases in the PR interval and the corrected QT interval and although the
      effects of rac-bupivacaine appeared to be greater the difference between the two
      drugs was not significant. CONCLUSIONS: In conclusion, this study has shown that
      following i.v. administration levobupivacaine produces significantly less effects
      on cardiovascular function than does rac-bupivacaine. In particular the negative
      inotropic effect for levobupivacaine was less than that for rac-bupivacaine as
      indicated by changes in stroke index, acceleration index and ejection fraction.

PMID- 9764966
TI  - Terfenadine and risk of acute liver disease.
AB  - AIMS: To estimate the risk of idiopathic acute liver disease among users of
      terfenadine. METHODS: We conducted a population-based cohort study based on the
      General Practice Research Database (GPRD) in the U.K. All persons who received at
      least one prescription for terfenadine during the period 1991 through 1995 were
      eligible for the study. Among these patients we identified all those with a
      diagnosis of a liver disorder requiring hospitalization or referral to a
      consultant within 60 days of a prior prescription for terfenadine. We obtained
      clinical records, including hospital discharge summaries, consultant reports and
      relevant laboratory results in order to identify a potentially drug-inducible
      liver illness. RESULTS: From a cohort of 210683 recipients of terfenadine, we
      found only three cases of acute liver disease where a causal connection to
      terfenadine could not be ruled out, yielding a risk estimate of 1.4/100000 users
      (95% CI 0.5, 4.2) and 0.5/100000 prescriptions (95% CI 0.2, 1.4). All cases were
      receiving a concomitant hepatotoxic drug and all had a full recovery. CONCLUSION:
      The use of terfenadine is rarely associated with idiopathic acute liver disease.

PMID- 9764967
TI  - Constipation as an adverse effect of drug use in nursing home patients: an
      overestimated risk.
AB  - AIMS: To investigate whether results from case control and cross sectional
      studies which suggest an association between laxative use and other drug use
      could be confirmed in a cohort study of nursing home patients. METHODS: A
      prospective cohort study of 2355 nursing home patients aged 65 years and over was
      performed to estimate the incidence relative risk of constipation associated with
      drug use. The study was conducted with prescription sequence analysis of each
      resident's detailed pharmacy records and data on morbidity and mobility. RESULTS:
      Use of drugs, which according to the summaries of product characteristics (SPC)
      and the literature on adverse drug effects have moderately to strongly
      constipating properties, was associated with a relative risk of 1.59 (95% CI 1.24
      2.04) for the occurrence of constipation during exposure time. Use of drugs with
      mildly to moderately constipating effects was not associated with laxative use
      (RR 1.13; 95% CI 0.93-1.38). Stratification on the level of age, gender, type of
      nursing (psychogeriatric or somatic), morbidity, number of medications taken and
      mobility showed no confounding effects of these variables on outcome
      measurements. These variables all acted as effect modifiers. Effect of age and
      number of medications taken on the relative risk was nonlinear. CONCLUSIONS:
      Although an association between drugs that exhibit moderately to strongly
      constipating effects and occurrence of constipation was found, the risk was not
      as high as seen in previous studies. The high prevalence of constipation in
      nursing home patients is only partly due to adverse drug effects.

PMID- 9764968
TI  - Nitric oxide: an important role in the maintenance of systemic and pulmonary
      vascular tone in man.
AB  - AIMS: The aim of this study was to examine whether nitric oxide (NO) has an
      important role in maintaining basal vascular tone in normal man by examining the
      effects of nitric oxide inhibition using N(G)-monomethyl-L-arginine (L-NMMA) on
      systemic and pulmonary haemodynamics. METHODS: Ten normal male volunteers 26 +/-
      1.6 years were studied on two separate occasions in a double-blind, placebo
      controlled crossover study. They were randomised to receive either a continuous
      infusion of L-NMMA (4 mg kg(-1) h(-1)) with a front loaded bolus (4 mg kg(-1)) or
      volume matched placebo. Pulsed wave Doppler echocardiography was used to measure
      cardiac output (CO), mean pulmonary artery pressure (MPAP) and hence systemic
      vascular resistance (SVR) and total pulmonary vascular resistance (TPR).
      Measurements were made prior to infusion (t0) and after 4, 8, and 12 min (t1, t2
      and t3). RESULTS: Infusion of L-NMMA significantly increased mean arterial blood
      pressure (MAP), SVR and TPR and significantly reduced heart rate (HR), stroke
      volume (SV) and CO compared to placebo. These effects were observed at t1 and
      persisted during the entire infusion period. CONCLUSIONS: These results are
      consistent with a role for basal nitric oxide generation in the maintenance of
      basal systemic and pulmonary vascular tone in normal man.

PMID- 9764969
TI  - Effect of age and gender on the pharmacokinetics of eprosartan.
AB  - AIMS: To compare the pharmacokinetics of eprosartan between young (18-45 years)
      and elderly (65 years) men and between young men and young, premenopausal women
      (18-45 years). METHODS: Twenty-four subjects (eight subjects/group) received a
      single 200 mg eprosartan oral dose followed by serial blood sampling over 24 h.
      RESULTS: Eprosartan was safe and well tolerated. There were no apparent
      differences in the pharmacokinetics of eprosartan between young females and young
      males or in the plasma protein binding of eprosartan (98%) for the three groups.
      On average, AUC (0,infinity) and Cmax values were approximately 2-fold higher in
      elderly men than young men [AUC (0,infinity) 95% CI: 1.22, 4.34; Cmax 95% CI:
      0.98, 4.001. Similarly, unbound AUC (0,infinity) and Cmax values were, on
      average, approximately 2-fold higher in elderly men than young men [unbound AUC
      (0,infinity) 95% CI: 1.29, 4.44; unbound Cmax 95% CI: 1.02, 4.12]. tmax was
      delayed in the elderly men compared with young men, with a median difference of
      2.5 h (95% CI: 1.00, 3.01 h). CONCLUSIONS: No gender differences were observed in
      the pharmacokinetics of eprosartan. There were approximately two fold higher AUC
      and Cmax values for eprosartan observed in elderly men as compared with young
      men, most likely due to increased bioavailability of eprosartan in the elderly.
      Based on the excellent safety profile in the elderly in Phase III clinical trials
      (doses up to 1200 mg eprosartan) eprosartan can be safely administered to elderly
      hypertensive patients without an initial dose adjustment. Subsequently, the dose
      of eprosartan, as for other antihypertensive agents, may be individualized based
      on tolerability/response.

PMID- 9764970
TI  - Evidence for a pharmacokinetic interaction between itraconazole and tacrolimus in
      organ transplant patients.

PMID- 9764971
TI  - Norfloxacin exhibits negligible serum concentrations after repeated conjunctival
      instillation in children.

PMID- 9764972
TI  - Lineage and development of the parasympathetic nervous system of the embryonic
      chick heart.
AB  - We were interested in the contribution of the cardiac neural crest to the
      complete anterior and posterior nerve plexus of the chick heart. This includes
      the pathways by which these cardiac neural crest-derived neuronal precursors
      enter the heart. As lineage techniques we used the traditional quail-chick
      chimera in combination with the newly introduced technique of retroviral reporter
      gene transfer to premigratory cardiac neural crest cells. Retrovirally infected
      embryos (n=23) and quail-chick chimeras (n=19) between stages HH27 and 40, were
      immunohistochemically evaluated, using the lineage markers LacZ (retroviral
      reporter) and QCPN (anti-quail nuclear marker), respectively and the neuronal
      differentiation markers HNK-1, RMO-270 and DO-170. Between stages HH27 and 33,
      quail-derived and LacZ positive cells were situated around the arterial cardiac
      vagal branches at the arterial pole, and vagal branches along the anterior
      cardinal veins and the sinal vagal branch at the venous pole. From stage HH35
      onward, QCPN/LacZ-positive cardiac ganglia were observed throughout the anterior
      and posterior plexus and were mainly concentrated in the subepicardium near the
      distal ends of the arterial cardiac vagal branches and the sinal cardiac vagal
      branch respectively. From stage HH36 both the anterior and posterior plexus
      contained a population of large cardiac ganglion cells and a population of
      smaller cells along nerve branches as well as in the cardiac ganglia, which means
      that differentiation starts in both plexus at the same time. Furthermore only
      nerve fiber connections between the anterior and posterior plexus were observed.
      These results show that the cardiac neural crest contributes to the cardiac
      ganglion cells from both the entire anterior and posterior plexus. Furthermore
      these results suggest that these precursor cells enter the arterial pole via the
      arterial cardiac vagal branches and the venous pole via the sinal cardiac vagal
      branch without intermixing. Finally we show that in addition to the cardiac
      ganglia, the cardiac neural crest contributes to small myocardial glia or
      undifferentiated cells along nerve fibers, and some myocardial nerve fibers as
      well as nerve tissue in the adventitia of the large veins at the venous pole and
      in the adventitia of the coronary arteries.

PMID- 9764973
TI  - Differences in axial curvature correlate with species-specific rate of neural
      tube closure in embryos of chick, rabbit, mouse, rat and human.
AB  - Studies on the mouse strain curly tail, a mutant for neural tube defects, have
      indicated that axial curvature is an important factor in neural tube closure.
      Previously reported results from experimental interventions in both mouse and
      chick embryos indicated that curvature along the craniocaudal axis and closure of
      the posterior neuropore (PNP) are inversely related, a correlation that is also
      proposed for the rabbit embryo. It was hypothesized that this relationship is a
      sign of a more general mechanism. Therefore, in the present report the number of
      species in which axial curvature is described along the craniocaudal axis was
      extended to include the rat and human. Next, the closure rate of the neural tube
      as well as the curvature of the PNP region was determined morphometrically for
      embryos of the following species: chick, rabbit, mouse, rat and human. Although
      the relationship between neural tube closure and axial curvature appeared
      specific for each species in the comparative analysis, a general association of
      increased rate of closure with a decreased curvature emerged. It is concluded
      that axial curvature is an important factor in neurulation.

PMID- 9764974
TI  - Septotemporal distribution of [3H]MK-801, [3H]AMPA and [3H]Kainate binding sites
      in the rat hippocampus.
AB  - The distribution of glutamate receptors in transverse hippocampal sections has
      been well investigated. However, in spite of the known septotemporal gradients of
      hippocampal connectivity no systematic studies exist about the distribution of
      glutamate receptors along the septotemporal (longitudinal) hippocampal axis.
      Therefore, in the present study this issue was investigated using receptor
      autoradiography for the [3H]MK-801, [3H]AMPA and [3H]Kainate binding sites.
      Hippocampi from 30-day-old rats were sectioned perpendicularly to their
      longitudinal axis, yielding a total of 25-30 equidistantly spaced autoradiographs
      for each hippocampus. For each section layer-specific concentrations of binding
      sites were calculated by the aid of a computerized image analysing system. The
      dependency of concentrations of binding sites on the septotemporal position was
      evaluated by regression analysis. Gradients of binding were confined to distinct
      hippocampal layers. Significant septotemporal gradients of [3H]MK-801 binding
      were observed in selected layers of CA1 and the dentate gyrus, a septal to
      temporal decrease of binding in the oriens and radiatum layers of CA1 being most
      prominent. For [3H]AMPA, significant septotemporal gradients of binding were
      restricted to layers of CA3, CA4 and the dentate gyrus, with values generally
      increasing from septal to temporal levels. The observed septotemporal gradients
      possibly reflect functional segregations along the longitudinal hippocampal axis
      and could be important for the comparability of ligand binding studies using
      transverse hippocampal sections or hippocampal slice cultures.

PMID- 9764975
TI  - Restricted distribution of S-phase cells in the anterior subventricular zone of
      the postnatal mouse forebrain.
AB  - The anterior subventricular zone (SVZa) is the site for postnatal neurogenesis of
      interneurons of the olfactory bulb (OB). Concurrently or after proliferation,
      neuronal precursors therein migrate within it to reach the OB, an event known as
      the rostral migratory stream (RMS). We used bromodeoxyuridine (BrdU)
      incorporation with short survival times to investigate the distribution of S
      phase nuclei in the SVZa/RMS of the postnatal mouse. We observed that they were
      distributed along a radial, outside-in, decreasing gradient that persisted until
      postnatal day 10 (P10), then faded away to finally disappear by P16. After longer
      post-injection survival times labeled cell distribution became homogeneous. GFAP
      positive glia are present at the periphery but not at the core of the SVZa. Our
      results represent the first evidence of a discrete spatial organization of a cell
      cycle phase within the SVZ, and also suggests a segregation of proliferating and
      migrating cells in the rostral migratory stream of the early postnatal mouse.

PMID- 9764976
TI  - Distribution of glial fibrillary acidic protein and vimentin-immunopositive
      elements in the developing chicken brain from hatch to adulthood.
AB  - The present study describes the distribution of glial fibrillary acidic protein
      (GFAP) and vimentin-immunopositive structures in the brain of the domestic
      chicken (Gallus domesticus) from hatching to maturity. The telencephalon is
      penetrated by a vimentin-immunopositive radial fibre system, representing a
      modified form of radial glia, in day-old chicks. Numerous fibres of this system
      persist until adulthood, mainly in the lobus parolfactorius, lamina medullaris
      dorsalis and lamina frontalis superior. GFAP immunoreactivity also appears in the
      course of development in these fibres. The distribution of GFAP-immunopositive
      astrocytes in the post-hatch telencephalon is like that found in adult chicken,
      except for the ectostriatum, in which an adult-like GFAP-immunostaining only
      develops during week three. This delay may be associated with a relatively slow
      maturation of this visual centre. In the diencephalon and in the mesencephalic
      tegmentum of day-old chicks GFAP-immunopositive astrocytes are confined to the
      border zone of several nuclei. In these areas as well as in the pons most GFAP
      positive astrocytes only appear gradually during the first two post-hatch weeks,
      although radial fibres occur only sparsely at hatch. Summarizing these results, a
      gradual replacement of radial fibres by astrocytes, typical of mammals, cannot be
      found in chicken. In the nucleus laminaris we observed a characteristic palisade
      of non-ependymal glia, reactive to GFAP but not to vimentin, which almost
      completely disappears by adulthood. We suggest that this glial system is
      instrumental in the development of the dendritic organisation of this nucleus.
      The optic tectum displays a dense array of GFAP-immunopositive radial glia at
      hatching, similar in this to the situation found in reptiles. However, in the
      tectum of reptiles this radial glia persists for the lifetime, whereas in the
      chick it disappears from the superficial tectal layers. This phenomenon may
      reflect the fact that there is no replacement of tectal cells or regeneration of
      retinotectal pathways in the chicken. In the early stage, the large cerebral
      tracts were found to contain dense accumulations of GFAP-positive cells, with
      peculiarly long outgrowths accompanying nerve fibres. No vimentin
      immunopositivity was found in these glial elements; however vimentin was present
      in the glia situated at the optic chiasm, the anterior commissure and at other
      decussations. These structures, as well as the raphe, displayed the most intense
      vimentin-immunopositivity in the post-hatch chicken. This characteristic glial
      population may represent glial elements that have been reported to regulate fibre
      crossing at the midline.

PMID- 9764977
TI  - Supraependymal cells and fibers during the early stages of chick rhombencephalic
      development.
AB  - Supraependymal cellular elements are a constant feature in the adult
      cerebroventricular system. However, there has been no analysis of their
      distribution and morphology during the embryonic stages of the chick brain. The
      ultrastructural features of the rhombencephalic luminal surface of chick embryos
      ranging from stage 10 to 22 were studied with both scanning and transmission
      electron microscopy. In addition, immunocytochemistry and confocal laser
      microscopy were used to examine the presence of 68 kD neurofilaments in
      supraependymal elements. The ultrastructural observations revealed significant
      morphological differences in the apical cell surface between the cells at
      rhombomere boundaries and those in the rhombomere bodies. These differences
      support the idea that the boundary and the body of rhombomeres contain two
      morphologically distinct cell types. Supraependymal (SE) cells and SE fibers were
      present in the rhombencephalon of all embryos studied from stage 12 to 22. The
      cells were bipolar spindle-shaped. The SE fibers showed a characteristic spatial
      pattern within the rhombencephalon, following a straight course parallel to the
      rhombomere boundaries. The SE fibers showed varicosities and their endings
      contained small vesicles. Both SE cells and SE fibers were positive for 68 kD
      neurofilaments. Their morphology and reactivity for neurofilaments indicate a
      neuronal function. The constant presence of SE cells and SE fibers on the surface
      of the developing rhombencephalon, their special pattern and close relationship
      with the neural tube fluid (NTF) suggest that these supraependymal elements may
      be involved in a neuronal signalling pathway between different parts of the same
      rhombomere and also in chemical communication and integration within the
      ventricular system, linking distant parts of the developing central nervous
      system by means of NTF.

PMID- 9764978
TI  - Effects of tri-iodothyronine (T3), insulin, insulin-like growth factor I (IGF-I)
      and transforming growth factor beta1 (TGFbeta1) on the proportion of insulin
      cells in cultured embryonic chick pancreas.
AB  - With a view to ultimately identifying factors involved in the development of
      pancreatic insulin cells, we have cultured dorsal pancreatic buds from 5-day
      chick embryos on a basement membrane matrix (Matrigel) in a serum-free medium
      supplemented with selected factors. The endodermal components of the buds were
      freed of almost all the mesenchyme so as to eradicate as much as possible of this
      source of some such factors. In 7-day cultures, insulin and glucagon cells were
      demonstrated immunocytochemically; numbers of insulin cells were expressed as a
      percentage of insulin plus glucagon cell counts. Our standard medium contained
      insulin. Addition of tri-iodothyronine to this medium did not increase the
      proportion of insulin cells, but in combination with raised concentrations of
      glucose and essential amino acids it improved somewhat the marked increase
      previously recorded for these nutrient conditions. Omission of insulin from the
      standard medium greatly reduced the proportion of these cells; substitution of
      insulin by insulin-like growth factor I increased the proportion considerably
      more than did insulin. To test for an overall effect of growth factors, explants
      were cultured in standard medium on Matrigel containing reduced amounts of growth
      factors: the proportion of insulin cells proved to be increased over that reached
      on normal Matrigel. The suspicion that transforming growth factor beta1, a
      component of Matrigel, might act to reduce the proportion of insulin cells was
      tested and found to be correct. It is suggested that the different factors
      studied here may affect either or both of proliferation and determination in the
      differentiation pathway of insulin vis-a-vis glucagon cells.

PMID- 9764980
TI  - The "interferon sensitivity determining region" of hepatitis C virus is a stable
      sequence element.
AB  - BACKGROUND/AIMS: A sequence of 40 amino acids within the nonstructural protein 5A
      of hepatitis C virus (HCV) has been suggested to be an interferon sensitivity
      determining region (ISDR). The variations in the ISDR after 12-14 years of
      chronic infection and the correlation between ISDR and interferon response were
      studied in patients who were infected by the same HCV isolate. METHODS: We
      determined the HCV-ISDRs of 13 chronically infected patients by direct sequencing
      of polymerase chain reaction products. All patients were infected by isolate HCV
      AD78, but differed with respect to their sensitivity to interferon. Four patients
      were complete responders, two patients were non-responders, and seven showed a
      partial response. RESULTS: The ISDR of HCV-AD78 differed from a prototypical HCV
      1b sequence in one amino acid and was therefore classified as an intermediate
      type. Direct sequencing of the HCV-ISDRs of the patients 12-14 years after
      infection, but before interferon therapy, revealed a rate of 2.2x10(-3)
      nucleotide substitutions per site per year, resulting in only single intermediate
      type amino acid exchanges. All sequences ranked with the intermediate type.
      Moreover, during interferon treatment no selection to a wild type ISDR was
      observed in five partial responders. CONCLUSIONS: Within the homogeneous patient
      group examined here, no correlation was found between the ISDR and the interferon
      response. Recent studies found only a small number of mutant type ISDRs in
      Europe. Additionally, our results indicate that the ISDR is a stable sequence
      element. This provides an explanation for the divergent data relating to the
      importance of the ISDR in different geographical regions.

PMID- 9764979
TI  - Core variability does not affect response to interferon alpha in HBeAg negative
      chronic hepatitis B.
AB  - BACKGROUND/AIMS: The pre-core stop codon variant (A 1896) of hepatitis B virus
      (HBV) has been associated with chronic active liver disease with acute
      exacerbations and a high relapse rate after an initial response to alpha
      interferon (IFN-alpha) therapy. Poor sustained response has been correlated with
      a high prevalence of mutations in the core region, potentially enabling escape
      from the immune system. The aim of this study was to analyse the predictive
      factors of response to IFN-alpha in such patients. METHODS: We studied the
      baseline clinical, biochemical, histological, serological and virological
      parameters in 30 hepatitis B s antigen positive (HBsAg-positive)/hepatitis B e
      antigen negative (HBeAg-negative) Greek patients with chronic liver disease. The
      patients were selected from a cohort who received IFN-alpha for 24 weeks. These
      were divided into three groups of ten sequential patients: those with no response
      to IFN-alpha treatment, those who relapsed after an initial response, and those
      with a sustained response. Serum HBV DNA was measured by a liquid hybridisation
      method, and the anti-HBc IgM was quantitated by the IMx analyser. The amino-acid
      sequence of core protein residues 40-89, a region where a clustering of mutations
      has been detected previously in severe hepatitis, was compared with a sequence
      from an HBeAg positive patient with chronic liver disease. RESULTS: Multiple
      logistic regression analysis showed that the initial response to IFN-alpha could
      be predicted by pre-treatment absence of HBcAg staining in the liver and high ALT
      values, but no parameter could predict sustained response. The pre-treatment
      extent and pattern of aminoacid substitutions in the core region sequenced was
      similar in all groups studied and was not associated with IFN-alpha response.
      CONCLUSIONS: In HBsAg-positive/HBeAg-negative patients with chronic liver
      disease, response to IFN-alpha therapy was not correlated with genomic
      variability of the core region. Other parameters such as pre-treatment HBcAg
      positivity in the liver and alanine aminotransferase values indicative of disease
      activity before treatment were associated with initial IFN-alpha response.

PMID- 9764981
TI  - Is there an optimal time to measure quantitative HCV RNA to predict non-response
      following interferon treatment for chronic HCV infection?
AB  - BACKGROUND/AIMS: Current criteria to predict sustained response for a patient
      with chronic hepatitis C virus during interferon treatment are not consistent.
      The aim of this study was to determine a reliable point in time to predict non
      response to therapy, as a theoretical basis for early cessation of treatment.
      METHODS: Sera (-70 degrees C) from 66 patients treated with interferon (3 million
      units three times a week for 6 months) were assayed with a quantitative
      polymerase chain reaction (sensitivity < or =100 copies per milliliter).
      Evaluations were made at baseline, during treatment at weeks 1, 2, 4, 12, and 24,
      and at follow-up week 48. Biochemical response was defined using standard alanine
      aminotransferase criteria. Virologic response was defined as: sustained if loss
      of HCV RNA persisted through therapy and follow-up; relapse if HCV RNA became
      undetectable but reappeared during treatment or follow-up; and non-response if
      HCV RNA remained detectable during the study period. Alanine aminotransferase and
      HCV RNA results were analyzed at defined time intervals to determine a predictive
      value for non-response and sustained response. RESULTS: HCV RNA results are a
      more accurate predictor than alanine aminotransferase for both non-response and
      sustained response. Serum HCV RNA predicted non-response better than sustained
      response. The optimal time to predict non-response with serum HCV RNA was
      treatment week 12. CONCLUSIONS: Treatment week 12 results indicate that HCV RNA
      was a more accurate predictor for non-response than serum alanine
      aminotransferase. This prediction would have theoretically permitted stopping
      treatment for 75% of the patients in this study at treatment week 12 allowing an
      overall cost savings of 28%.

PMID- 9764982
TI  - Treatment of chronic hepatitis C with alpha-interferon plus ofloxacin in patients
      not responding to alpha-interferon alone.
AB  - BACKGROUND/AIMS: Ofloxacin, a quinolone antibiotic, was recently shown to
      increase the primary response rate to alpha-interferon treatment of chronic
      hepatitis C. METHODS: Fifty-five patients with chronic hepatitis C were scheduled
      to receive 3 MU of a-interferon, three times a week, for 1 year. After 3 months
      of therapy, patients who were still HCV RNA-positive in serum started receiving a
      combined regimen with 3 MU of alpha-interferon, three times a week, plus
      ofloxacin, 600 mg daily, per os. After 3 months of combined therapy, patients
      with undetectable serum HCV RNA continued the combined regimen for another 6
      months, whereas patients who were still HCV RNA-positive were definitively
      considered as non-responders and withdrawn from the study. Serum HCV RNA levels
      were quantitatively evaluated after 3 months of therapy with a-interferon alone
      and compared with those detected after 3 months of combined regimen. RESULTS:
      Among the 54 patients who completed the first 3 months of treatment, 32 (59.3%)
      still had HCV RNA detectable in serum and started receiving the ofloxacin/alpha
      interferon therapy. Among the 26 patients who completed the 3 additional months
      of combined regimen, only one showed a virological response: this patient
      maintained a complete response to the end of combined treatment, but relapsed
      thereafter. The combination therapy had no effect on the serum HCV RNA or alanine
      aminotransferase levels. CONCLUSIONS: The combined administration of alpha
      interferon and ofloxacin to patients with chronic hepatitis C who have not
      responded to alpha-interferon alone does not increase the primary virological
      response rate.

PMID- 9764983
TI  - A clinical and virological study of hepatitis C virus-related cryoglobulinemia in
      Germany.
AB  - BACKGROUND/AIMS: Several reports, especially from Southern Europe, have
      demonstrated a close association between hepatitis C virus (HCV) infection and
      mixed cryoglobulinemia. In this study we have analyzed the significance of HCV
      related cryoglobulinemia in Germany. METHODS: Sera from 79 patients with
      cryoglobulinemia of type I (n=21), II (n=28) or III (n=30) were investigated for
      HCV markers. Furthermore, 132 consecutive patients with chronic hepatitis C were
      studied for the presence of cryoglobulins. Genotypes of HCV were determined
      according to Simmonds, and HCV-RNA concentrations were measured in patients with
      and without cryoglobulinemia. RESULTS: In 79 patients with cryoglobulinemia we
      found anti-HCV antibodies in 17 (22%) and HCV-RNA in 11 patients (14%). HCV
      antibodies were more frequent in essential (44%) compared to secondary mixed
      cryoglobulinemia (15%). In 132 patients with chronic HCV infection cryoglobulins
      were detected in 37 patients (28%), in 21 of them at low levels. Clinical
      symptoms due to cryoglobulinemia were observed in eight of the 37 patients,
      severe vasculitis in three patients with high cryocrit-levels and
      cryoprecipitation at room temperature. HCV genotype 1 and subtype 1b were most
      prevalent, both in patients with and without cryoglobulinemia, and mean HCV-RNA
      levels were not different between the two groups. Comparison of HCV-RNA levels in
      cryoprecipitates, supernatant and native serum suggests binding of HCV-RNA to the
      cryoprecipitate with different affinity in individual patients. CONCLUSIONS: The
      lower prevalence of HCV-related cryoglobulinemia in our study compared with data
      from Italy and France suggests a south-north gradient in the prevalence of HCV
      associated cryoglobulinemia in Europe.

PMID- 9764984
TI  - In vitro inhibition of the hepatitis delta virus replication mediated by
      interferon and trans-ribozyme or antisense probes.
AB  - BACKGROUND/AIMS: In this study, the inhibition of hepatitis delta virus
      replication mediated by trans-ribozyme and antisense probes, alone or in
      combination with recombinant interferon alpha-2a, has been assayed. METHODS: A 60
      nucleotide-long designed trans-ribozyme, which contains the catalytic core of the
      hammerhead ribozyme, and a 163-nucleotide-long antisense probe were directed
      against the same region of the viral genome in in vitro and cell culture systems.
      RESULTS: The ribozyme activity, assayed in a chemically isolated system, resulted
      in the trans-cleavage of 10-20% of the 40-nucleotide-long RNA substrate. A 5
      nucleotide deletion in one of the flanking arms, obtained by random mutagenesis,
      resulted in enhancement of the trans-cleavage activity in as many as 40-60% of
      the substrate molecules. The efficiency of the optimized trans-ribozyme and
      antisense probes against the complete viral genome was assayed in a cell culture
      system. The inhibitory efficacy (25%) of the trans-ribozyme is lower than that of
      the antisense probe (35%) or interferon at 1000 U/ml (47%). An enhancement of the
      interferon efficacy was achieved when it was administered in cells having a
      previous basal expression of ribozyme (70%) or antisense probes (83%).
      CONCLUSIONS: These results suggest that the combination of ribozyme or antisense
      probes with interferon could be a promising approach to the treatment of RNA
      virus infections.

PMID- 9764985
TI  - Ecstasy: a common cause of severe acute hepatotoxicity.
AB  - BACKGROUND/AIMS: Ecstasy is a synthetic amphetamine recently identified as a
      possible cause of acute liver injury. This drug is consumed by young people and
      has a marked effect on improving sociability. The extent of ecstasy-associated
      severe hepatic damage is unknown to date. METHODS: The clinical histories of 62
      patients with acute liver failure admitted to the Intensive Care Liver Unit
      between January 1994 and December 1996 were reviewed to assess the frequency, the
      epidemiological, clinical and histological characteristics and the outcome of
      ecstasy-induced severe hepatitis. RESULTS: Over this period of time, five
      patients (8%) were admitted because of ecstasy-induced acute liver failure,
      representing 31% of the cases with drug hepatotoxicity. Ecstasy was the second
      most common cause of liver injury in patients under the age of 25 years, being
      20% in this subset of patients and 36% after ruling out the cases of viral
      etiology. All the patients had severe liver disease of acute onset, with
      jaundice, high peak of serum transaminases activity, hypoglycemia and low
      prothrombin activity, but no hepatic encephalopathy. Full recovery was observed
      in all cases from 3 to 12 months. CONCLUSIONS: Ecstasy is responsible for a
      relatively high number of cases of acute liver failure in young people.
      Therefore, the use of this drug should be investigated in all patients with
      severe hepatitis of unclear origin. Efforts must be made to advise young people
      of the risks of ecstasy consumption.

PMID- 9764986
TI  - Contraction of human hepatic stellate cells activated in culture: a role for
      voltage-operated calcium channels.
AB  - BACKGROUND/AIMS: Voltage-operated calcium channels are essential for the
      regulation of vascular tone and are potential targets for vasodilating agents.
      They regulate calcium entry and thereby cell contraction in vascular cell types.
      Hepatic stellate cells in the activated phenotype have contractile properties and
      could participate in the regulation of sinusoidal blood flow. Thus, this study
      was aimed at investigating the presence of voltage-operated calcium channels in
      human hepatic stellate cells activated in culture and the effects of their
      stimulation on intracellular calcium concentration ([Ca2+]i) and cell
      contractility. METHODS: Binding studies using [3H]-nitrendipine were performed to
      demonstrate the presence of voltage-operated calcium channels. Voltage-operated
      calcium channels were stimulated by causing cell membrane depolarization either
      by electrical field stimulation or extracellular high potassium. [Ca2+]i and cell
      contraction were measured in individual cells loaded with fura-2 using a
      morphometric method with an epifluorescence microscope coupled to a charge
      coupled device-imaging system. RESULTS: Binding studies demonstrated the
      existence of voltage-operated calcium channels in human activated hepatic
      stellate cells (7.1+/-1.4x10(4) sites/cell with a Kd of 2.1+/-0.1 nM). Both
      electrical field stimulation and potassium chloride-induced cell depolarization
      resulted in a marked and prolonged increase in [Ca2+]i followed by intense cell
      contraction. The degree of cell contraction correlated with the intensity of
      calcium peaks. Removal of extracellular calcium or preincubation of cells with
      nitrendipine, a specific antagonist of voltage-operated calcium channels,
      completely blocked the effects on [Ca2+]i and cell contraction, whereas
      preincubation of cells with BayK-8644, a specific agonist of voltage-operated
      calcium channels, increased calcium peaks and contraction. CONCLUSION: Activated
      human hepatic stellate cells have a large number of voltage-operated calcium
      channels, the activation of which is associated with an increase in [Ca2+]i
      followed by marked cell contraction. Voltage-operated calcium channels probably
      play an important role in the regulation of activated hepatic stellate cells
      contractility.

PMID- 9764987
TI  - Abnormal accumulation of endotoxin in biliary epithelial cells in primary biliary
      cirrhosis and primary sclerosing cholangitis.
AB  - BACKGROUNDS/AIMS: Previous studies have revealed the involvement of Kupffer cells
      and hepatocytes in the metabolism of endotoxin in the liver. The aim of this
      study was to investigate the in vivo localization of endotoxin in liver cells,
      including Kupffer cells, hepatocytes, and biliary epithelial cells, in primary
      biliary cirrhosis and primary sclerosing cholangitis. We also examined the effect
      of ursodeoxycholic acid on the intrahepatic distribution of endotoxin in primary
      biliary cirrhosis. METHODS: The immunohistochemical localization of endotoxin was
      examined in liver specimens from 30 cases of primary biliary cirrhosis and seven
      of primary sclerosing cholangitis using a monoclonal antibody against lipid A.
      Controls were seven cases of obstructive jaundice, ten of hepatitis C virus
      related liver cirrhosis, 14 of chronic hepatitis C, and five histologically
      normal liver cases. Semi-quantitative analysis of endotoxin accumulation was
      performed to measure the intensity of fluorescence for endotoxin. Nine of the 30
      patients with primary biliary cirrhosis underwent a second liver biopsy for
      evaluation of the ursodeoxycholic acid treatment. RESULTS: In primary biliary
      cirrhosis and primary sclerosing cholangitis, biliary epithelial cells showed
      strong immunostaining for endotoxin as well as hepatocytes and Kupffer cells.
      Biliary epithelial cells of primary biliary cirrhosis and primary sclerosing
      cholangitis showed more intense immunoreactivity than those of other controls. In
      primary biliary cirrhosis, ursodeoxycholic acid reduced the immunoreactivity to
      endotoxin in biliary epithelial cells, and increased the immunoreactivity to
      endotoxin in Kupffer cells, but did not affect that in hepatocytes. CONCLUSIONS:
      Our results revealed that in primary biliary cirrhosis and primary sclerosing
      cholangitis, endotoxin accumulates abnormally in biliary epithelial cells. In
      addition, we found that ursodeoxycholic acid treatment in primary biliary
      cirrhosis may provide a beneficial effect on the intrahepatic metabolism of
      endotoxin.

PMID- 9764989
TI  - Polyethylene glycol-modified bilirubin oxidase improves hepatic energy charge and
      urinary prostaglandin levels in rats with obstructive jaundice.
AB  - BACKGROUNDS/AIMS: No study has so far been conducted to clarify whether the
      presence of hyperbilirubinemia is detrimental to liver and renal functions. In
      the present study, the effects of polyethylene glycol-modified bilirubin oxidase
      (PEG-BOX) therapy on liver and renal function tests, hepatic energy charge and
      urinary prostaglandin levels were evaluated in a rat model of obstructive
      jaundice. METHODS: Sprague-Dawley rats were used in the experimental model of
      obstructive jaundice. PEG-BOX or an equivalent amount of PEG alone was
      intravenously injected into the animals and sampling of blood and urine, and
      liver harvesting were done sequentially after bile duct ligation. RESULTS:
      Conventional liver function tests showed no difference between PEG-BOX and
      control groups. However, bilirubin concentrations in the peripheral blood and
      liver tissue specimens markedly decreased, and the hepatic energy charge
      significantly increased in the PEG-BOX group as compared to controls. The blood
      concentration of bile acid was lower, but its urinary excretion was higher in the
      PEG-BOX group than in the control group. In vitro incubation of PEG-BOX with
      serum from rats with obstructive jaundice decreased the concentration of
      bilirubin but not that of bile acid. The urinary levels of prostaglandin E2 and
      the thromboxane B2/6-keto-prostaglandin Fla ratio were significantly lower in the
      PEG-BOX group than in the control group. CONCLUSIONS: The systemic reduction of
      bilirubin concentration may contribute to normalization of the urinary levels of
      prostaglandins and thromboxane B2, to decrease in serum bile acid levels, and to
      improvement of the hepatic energy charge in obstructive jaundice. These findings
      suggest that preoperative improvement of jaundice may be beneficial to patients
      with obstructive jaundice.

PMID- 9764988
TI  - Ursodeoxycholic acid therapy for primary sclerosing cholangitis: results of a 2
      year randomized controlled trial to evaluate single versus multiple daily doses.
AB  - BACKGROUND/AIMS: Ursodeoxycholic acid has been reported to be of potential
      benefit for primary sclerosing cholangitis but little is known about the long
      term biochemical, histological and radiological efficacy or the optimum frequency
      of ursodeoxycholic acid administration. METHODS: A 2-year multicentre randomised
      controlled trial was initiated to assess the effects of ursodeoxycholic acid (10
      mg kg(-1).d(-1), given in either single or multiple daily doses, on symptoms,
      serum liver tests, cholangiographic and histological findings and the occurrence
      of treatment failure. Liver biopsies were taken and endoscopic retrograde
      cholangiography was performed at entry and after 2 years; follow-up examinations
      were at 3-month intervals. Treatment failure was defined as death, liver
      transplantation, 4-fold increase in serum bilirubin, variceal bleeding, de novo
      ascites or cholangitis. Actuarial survival was compared with predicted survival
      using the revised Mayo natural history model for primary sclerosing cholangitis.
      RESULTS: Forty-eight patients were enrolled. In one case, ursodeoxycholic acid
      had to be discontinued because of gastro-intestinal complaints. No other side
      effects were observed. After 2 years of follow-up, treatment was not associated
      with a beneficial effect on either symptoms or liver histology. Serum liver tests
      (alkaline phosphatase, y-glutamyl transferase, aspartate aminotransferase)
      improved significantly in both groups, while serum bilirubin (which was near
      normal at entry) and IgG remained stable. No major changes in radiographic bile
      duct appearance seemed to be present. After 2 years, actuarial survival was 91%
      (95 CI 83%-99%), which is comparable to the predicted 97% survival rate.
      Treatment failure occurred in 15% of cases. No significant differences in any of
      the study endpoints (symptoms, serum liver tests, cholangiographic findings,
      histology, disease progression) were found between the two groups. CONCLUSIONS:
      Ursodeoxycholic acid is well tolerated in primary sclerosing cholangitis.
      Significant effects on biochemical parameters were found and symptoms, bilirubin
      and histology did not deteriorate. No advantage of a multiple daily dose over a
      single dose was observed.

PMID- 9764990
TI  - Norfloxacin primary prophylaxis of bacterial infections in cirrhotic patients
      with ascites: a double-blind randomized trial.
AB  - BACKGROUND/AIMS: Norfloxacin is useful to prevent infections in hospitalized
      cirrhotic patients with low ascitic fluid protein concentrations. It is also
      effective in preventing the recurrence of spontaneous bacterial peritonitis. The
      aim of our study was to determine the efficacy of norfloxacin in the primary
      prophylaxis of gram-negative bacilli infections in cirrhotic patients with low
      ascitic fluid protein levels (<15 g/l). METHODS: One hundred and seven patients
      were randomized to receive norfloxacin (400 mg/day; n=53) or placebo (n=54) for 6
      months. The patients had no history of infection since cirrhosis diagnosis and no
      active infection. RESULTS: The probability of gram-negative infection was
      significantly lower among patients treated with norfloxacin than among those
      treated with placebo. Six gram-negative bacilli infections occurred in the
      placebo group and none in the treatment group. Severe infections (spontaneous
      bacterial peritonitis, neutrocytic ascites and bacteremia) developed in nine
      patients in the placebo group (17%) and in one patient in the norfloxacin group
      (2%; p<0.03). There was no between-group difference in the overall rate of
      infection or in survival. In ten patients from the norfloxacin group, gram
      negative bacilli not present in baseline stool cultures were transiently isolated
      in follow-up cultures. CONCLUSIONS: These data show that primary prophylaxis with
      norfloxacin for 6 months is effective in the prevention of infections caused by
      gram-negative bacilli in cirrhotic patients with low ascitic fluid total protein
      levels.

PMID- 9764991
TI  - Effects of oral ciprofloxacin on aerobic gram-negative fecal flora in patients
      with cirrhosis: results of short- and long-term administration, with daily and
      weekly dosages.
AB  - BACKGROUND/AIMS: Selective intestinal decontamination has been proposed to
      prevent spontaneous bacterial peritonitis in cirrhosis. Because of the cost of
      antibiotics and the development of resistant bacteria, we have evaluated the
      effect of different schemes and doses of oral ciprofloxacin on aerobic gram
      negative fecal flora in cirrhotic patients. METHOD: Twenty-nine cirrhotic
      patients were allocated to four groups to receive: Group 1: 500 mg/day for 2
      weeks (six patients); Group 2: 1000 mg twice a week for 2 weeks (six patients);
      Group 3: 1000 mg once a week for 2 weeks (six patients); and Group 4: 1000 mg
      once a week for 12 weeks (11 patients). Quantitative analysis of the gram
      negative fecal flora was performed before and 1 and 2 weeks after initiation of
      treatment in patients in Groups 1, 2 and 3 and before and 4, 8 and 12 weeks after
      initiation of treatment in patients in Group 4. RESULTS: Complete eradication of
      gram-negative bacilli was observed in four of six patients in Group 1. In
      contrast, only one patient eradicated gram-negative bacilli in Group 2 and Group
      3. In long-term administration of ciprofloxacin (Group 4), only two of 11
      patients had persistent eradication of gram-negative bacilli. Four patients
      developed E. coli resistant to ciprofloxacin (one of them associated to resistant
      Klebsiella). No patient developed bacterial infection during the study period.
      CONCLUSION: Oral ciprofloxacin administered in a weekly dose is ineffective in
      selective intestinal decontamination. Different mechanisms, including the
      emergence of ciprofloxacin-resistant organisms, could account for this failure.
      Therefore, our results suggest that weekly administration of ciprofloxacin is not
      useful in preventing spontaneous bacterial peritonitis.

PMID- 9764992
TI  - Bright basal ganglia in T1-weighted magnetic resonance images are frequent in
      patients with portal vein thrombosis without liver cirrhosis and not suggestive
      of hepatic encephalopathy.
AB  - BACKGROUND/AIMS: Deposition of paramagnetic substances in basal ganglia,
      resulting in increased signals in T1-weighted magnetic resonance images (bright
      basal ganglia), is frequently seen in liver cirrhosis. The present study
      describes the prevalence of bright basal ganglia and its clinical significance in
      patients with long-standing portal vein thrombosis in the absence of liver
      cirrhosis. METHODS: Six patients with angiographically proven complete portal
      vein thrombosis and cavernomatous transformation without signs of acute or
      chronic liver disease were studied by magnetic resonance imaging of the brain,
      neuropsychiatric evaluation, psychometric tests, electroencephalography, and
      determination of arterial ammonia levels and of serum manganese concentrations
      from peripheral venous blood. RESULTS: Five out of six patients demonstrated
      increased signal intensity in the basal ganglia. Overt portal-systemic
      encephalopathy was not noted prior to or at the time of evaluation. Normal EEG
      results were recorded in all patients. Only one of the six patients had
      pathological results in at least two out of four psychometric tests. This latter
      patient had had a large right-sided brain infarction. Arterial ammonia
      concentrations were normal in four of the six patients; one patient with
      increased ammonia levels had concomitant renal insufficiency with azotemia. The
      other four patients had no relevant concomitant diseases. Serum manganese levels
      were non-significantly increased compared with a control group (p=0.06), but they
      were significantly correlated to basal ganglia signal intensity (R=0.88; p=0.02).
      CONCLUSIONS: Our results demonstrate that bright basal ganglia primarily
      represent shunt-induced alterations. They are not directly associated with
      disturbed liver function nor with portal-systemic encephalopathy.

PMID- 9764994
TI  - Hepatic OV-6 expression in human liver disease and rat experiments: evidence for
      hepatic progenitor cells in man.
AB  - BACKGROUND/AIMS/METHODS: Since in rat experiments, activation of progenitor cells
      is seen in conditions associated with hepatocyte injury or inhibited replication,
      we compared the activation and fate of human putative progenitor cells in
      regenerating liver versus chronic cholestatic disease, using
      immunohistochemistry, rat oval cell marker OV6 and a panel of bile ductular cell
      markers. We compared the results with different rat models: the choline-deficient
      acetylaminofluorene (CDAAF)- and alpha-naphthylisothiocyanate (ANIT)-model, using
      immunohistochemistry and electron microscopy. RESULTS: In very early stages of
      human liver regeneration, putative progenitor cells in the vicinity of portal
      tracts were immunoreactive for OV6, CK7, CK19 and chrom-A. In later stages of
      regeneration and in chronic cholestasis, reactive bile ductules (immunoreactive
      for OV6, CK7, CK19, chrom-A, NCAM) and intermediate hepatocyte-like cells
      (immunoreactive for OV6, CK7, chrom-A), became apparent, suggesting bidirectional
      differentiation of the putative progenitor cells. In regenerating human liver,
      intermediate hepatocyte-like cells became more numerous with time and extended
      far into the lobule. In advanced cholestasis, intermediate hepatocyte-like cells
      were less numerous and formed periportal rosettes and small clusters. In the
      CDAAF rat model (associated with inhibited hepatocyte replication), but not in
      the ANIT model, gradual differentiation of oval cells into hepatocytes was seen
      after stopping the diet. CONCLUSIONS: Our results in human liver suggest that
      reactive ductules and intermediate hepatocyte-like cells originate at least
      partly from activation and differentiation of "progenitor cells". In regeneration
      after submassive necrosis, in analogy with what is seen in rat models,
      differentiation towards hepatocytes is more pronounced than in chronic
      cholestasis.

PMID- 9764993
TI  - Isolation from human fetal liver of cells co-expressing CD34 haematopoietic stem
      cell and CAM 5.2 pancytokeratin markers.
AB  - BACKGROUND/AIMS: Ductal plate and bile duct cells in developing human liver
      express haematopoietic stem cell markers, such as c-kit and CD34, in association
      with cytokeratin markers CAM 5.2 and CK 18. The identification of such ductal
      plate cells as likely progenitors for both bile duct epithelial cells and
      hepatocytes and their possible reappearance as oval cells in the regenerating
      liver have generated much interest in their pluripotential capacities. This study
      aimed to isolate cells from human fetal liver that co-express haematopoietic stem
      cell and epithelial cell markers. METHODS: Human fetal liver was harvested
      following legal termination of pregnancy at week 14-22. CD34+ mononuclear cells
      were isolated from liver cell suspensions with immunomagnetic beads.
      Immunofluorescent staining, using anticytokeratin CAM 5.2 against CK 8 and 18,
      was performed on permeabilised CD34+ cells for flow cytometry and fluorescent
      microscopy. CD34+ cells were also stained for other stem cell markers (HLA-DR, c
      kit) and committed haematopoietic cell markers (CD33, CD38). RESULTS:
      Approximately 0.9% (range 0.07-4.0%) of the mononuclear cells isolated were CD34+
      cells. The number of mononuclear cells isolated correlated with fetal liver
      weight (r=0.508). About 3-8% of these CD34+ cells stained positively for CAM 5.2.
      In addition, CD34+ cells were positive for HLA-DR, but only a small percentage
      was positive for c-kit. Staining for the committed haematological markers, CD33
      and CD38, was consistently negative. CONCLUSIONS: This study describes an
      immunoaffinity method for the enrichment from human fetal liver of cells that co
      express haematopoietic stem cell and epithelial cell markers. Such cellular
      subsets may correspond to pluripotential ductal plate and bile duct cells.

PMID- 9764995
TI  - Time course of cell cycle-related protein expression in diethylnitrosamine
      initiated rat liver.
AB  - BACKGROUND/AIMS: Cell cycle control and the relationship that exists between
      cellular proliferation, the expression of cell cycle control proteins and cancer
      have been reported. This study was designed to decipher the timing of cell cycle
      control protein expression during the initiation of diethylnitrosamine-induced
      rat hepatocarcinogenesis. METHODS: Three-week-old female Sprague-Dawley rats were
      intraperitoneally injected twice in 1 week with diethylnitrosamine; after the
      second injection, all animals were sacrificed at 1, 2 and 24 h, and 3 and 7 days.
      The expression of cell cycle-related proteins such as CDK2 and 4, cyclin proteins
      (D1, E and cdc2), proliferating cell nuclear antigen, tumor suppressor proteins
      (p53 and Rb), CDK inhibitory proteins (p21waf1 and p27Kip1), and apoptosis
      inhibiting protein (bcl-2) following diethylnitrosamine treatment was examined.
      RESULTS: The peak induction time of each cell cycle-related protein during DEN
      induced cellular proliferation was diverse, and expressions of CDK2, CDK4, cdc2,
      p53, bcl-2, p21Waf1 and p27Kip1 appear to be of the greatest interest.
      CONCLUSIONS: Data generated from this study may provide information about cell
      cycle-related protein expression in the initiation stage of hepatocarcinogenic
      signaling pathways stimulated by a genotoxic agent such as diethylnitrosamine.

PMID- 9764996
TI  - Angioarchitecture and blood circulation in focal nodular hyperplasia of the
      liver.
AB  - BACKGROUND/AIMS: We sought to clarify important unresolved points regarding
      angioarchitecture and blood circulation in focal nodular hyperplasia. METHODS:
      Twenty-nine surgically resected focal nodular hyperplasia lesions were examined
      histologically, immunohistochemically, and radiologically. In three autopsy
      cases, red- and blue-colored gelatin was injected into the hepatic artery and the
      portal vein, respectively, to demonstrate the vasculature in focal nodular
      hyperplasia. RESULTS: Histologically, no orientation with respect to portal
      tracts and central veins was evident in any lesion. Within lesions, vessels were
      classified as: (i) anomalous arteries in the fibrous septa, (ii) capillaries in
      the fibrous septa, or (iii) venous vessels located mainly in the parenchyma.
      Vessels and sinusoids adjacent to fibrous septa were stained for CD 34 and von
      Willebrand factor. The anomalous arteries were connected to the capillaries.
      Capillaries in the fibrous septa were connected to sinusoids adjacent to fibrous
      septa. Venous vessels were connected to central or hepatic veins surrounding the
      lesions. Intranodular sinusoids were connected to the sinusoids in the
      surrounding normal liver. Red-colored gelatin, injected at autopsy into the
      hepatic artery, appeared not only in the anomalous arteries but also in
      capillaries and in sinusoids adjacent to the fibrous septa of the lesion.
      Angiography clearly depicted hepatic veins located near the lesions in nine
      cases. Computed tomography during arterial portography disclosed no portal blood
      flow in the lesions. CONCLUSIONS: In focal nodular hyperplasia, arterial blood
      flows from the anomalous arteries via the capillaries into sinusoids adjacent to
      fibrous septa. The blood in the sinusoids drained to the hepatic vein either
      directly or via perinodular sinusoids.

PMID- 9764997
TI  - Kinetic analysis of vascular marker distribution in perfused rat livers after
      regeneration following partial hepatectomy.
AB  - BACKGROUND/AIMS: Liver clearance models are based on information (or assumptions)
      on solute distribution kinetics within the microvasculatory system. The aim was
      to study albumin distribution kinetics in regenerated livers and in livers of
      normal adult rats. METHODS: A novel mathematical model was used to evaluate the
      distribution space and the transit time dispersion of albumin in livers following
      regeneration after a two-thirds hepatectomy compared to livers of normal adult
      rats. Outflow curves of albumin measured after bolus injection in single-pass
      perfused rat livers were analyzed by correcting for the influence of catheters
      and fitting a long-tailed function to the data. RESULTS: The curves were well
      described by the proposed model. The distribution volume and the transit time
      dispersion of albumin observed in the partial hepatectomy group were not
      significantly different from livers of normal adult rats. CONCLUSIONS: These
      findings suggest that the distribution space and the transit time dispersion of
      albumin (CV2) is relatively constant irrespective of the presence of rapid and
      extensive repair. This invariance of CV2 implies, as a first approximation, a
      similar degree of intrasinusoidal mixing. The finding that a sum of two (instead
      of one) inverse Gaussian densities is an appropriate empirical function to
      describe the outflow curve of vascular indicators has consequences for an
      improved prediction of hepatic solute extraction.

PMID- 9764998
TI  - Lipoamide dehydrogenase deficiency: a newly discovered cause of acute hepatitis
      in adults.
AB  - Lipoamide dehydrogenase deficiency is a rare disease, manifested in early
      childhood by lactic acidemia, progressive neurological damage and death in most
      cases. We report a case of lipoamide dehydrogenase deficiency in a 34-year-old
      Ashkenazi-Jewish woman. The deficiency manifested as acute hepatitis without
      cognitive impairment or acidosis. The patient's brother also had lipoamide
      dehydrogenase deficiency, diagnosed at the age of 20, and manifested as
      hepatocellular damage, lactic acidemia and myoglobinuria. We assume that the
      trigger for this hepatocellular damage was prolonged fasting, and that otherwise
      the patient might have gone undiagnosed. Other cases in Ashkenazi Jews of mild
      lipoamide dehydrogenase deficiency with hepatocellular injury but without central
      nervous system involvement are reviewed.

PMID- 9764999
TI  - Primary lymphoma of the liver with bile duct invasion and tumoral occlusion of
      the portal vein: report of a case.
AB  - A 55-year-old woman presented to hospital with epigastric pain and jaundice.
      Diagnostic imaging studies revealed a biliary stricture of the hepatic confluence
      and a hepatic tumour of the left and caudate lobes with a portal tumour thrombus,
      which occupied the main portal trunk, the umbilical portion of the left portal
      vein, and the right anterior and posterior portal branches. Left hepatic
      trisegmentectomy, caudate lobectomy, portal tumour thrombectomy, bile duct
      resection and bilioenteric anastomosis were performed. There were no other
      lesions, and so it was diagnosed as a primary lymphoma of the liver (B-cell,
      diffuse, large cell type). The patient underwent postoperative chemotherapy and
      has remained well for 4.5 years after surgery. Primary lymphoma of the liver is
      very rare, and this is the first case report with bile duct invasion and tumoral
      occlusion of the portal vein.

PMID- 9765000
TI  - Wilson's disease before and after 5 years of treatment with D-penicillamine.

PMID- 9765002
TI  - Non-alcoholic steatohepatitis (NASH): a disease of emerging identity and
      importance.

PMID- 9765001
TI  - Antibiotic prophylaxis for spontaneous bacterial peritonitis: how and whom?

PMID- 9765003
TI  - Hemochromatosis 1998: is one gene enough?

PMID- 9765004
TI  - Clinical impact of lamivudine resistance in chronic hepatitis B.

PMID- 9765005
TI  - Long-term efficacy of interferon alpha treatment in chronic hepatitis C.

PMID- 9765006
TI  - Increased serum nitrite and nitrate concentrations in chronic hepatitis.

PMID- 9765007
TI  - Hepatocellular carcinoma in patients suffering from primary sclerosing
      cholangitis.

PMID- 9765008
TI  - Malpractice claims for permanent nerve injuries related to third molar removals.
AB  - On the basis of the register of the Finnish Patient Insurance Association, the
      aim of this study was to examine malpractice claims for nerve injuries associated
      with third molar removals and determine whether they are concentrated among
      specialists, among less experienced dentists, or in certain geographic areas.
      During 1987-93 there were 139 claims for permanent sensory or motor disturbances
      related to removal of lower third molars in Finland. The lingual nerve was
      injured in 54% and the inferior alveolar nerve in 41% of the claims. In 91% of
      the cases the injury occurred in relation to surgical removal of the tooth and in
      6% in relation to simple extraction. The claims were distributed among 123
      dentists, of whom 78% were dental surgeons, 15% specialists in oral and
      maxillofacial surgery, and 7% other specialists. These figures represented 2% of
      the dental surgeons and 26% of the oral surgeons in Finland (P< 0.01). More than
      half the claims were associated with dentists with less than 10 years'
      experience. Claims originated more often from the eastern and northern (rural)
      areas of Finland than from urban areas (3.8 claims versus 2.4 claims per 100,000
      inhabitants, P < 0.05). Compensation was paid to the patients in two-thirds of
      the cases, indicating that the dentists authorized to decide claims very often
      considered these injuries avoidable. Therefore, proper diagnosis, treatment
      planning, surgical techniques, and detailed patient information must be
      emphasized. In cases where risks are obvious, referral to an oral surgeon is
      recommended.

PMID- 9765009
TI  - Effect of NaF-, SnF2-, and chlorhexidine-impregnated birch toothpicks on mutans
      streptococci and pH in approximal dental plaque.
AB  - The antimicrobial effect of birch toothpicks impregnated with 4% NaF, 8% SnF2, or
      2% chlorhexidine was studied both in vitro and in vivo. A non-impregnated
      toothpick served as a control. In vitro, suspensions of Streptococcus mutans were
      exposed to the various toothpicks for 20 min and then cultured on blood agar. The
      results of this susceptibility test revealed the following ranking order with
      respect to inhibition: chlorhexidine > SnF2 > NaF and non-impregnated; with
      significant differences in colony-forming units (CFU) between these three groups.
      In vivo, 12 individuals used the 4 types of toothpick 3 times a day for 5 days in
      a procedure with a crossover design. Saliva and approximal plaque samples were
      collected at baseline and on various occasions up to 23 days after the treatment.
      At the same time, plaque-pH was measured at approximal sites 10 min after rinsing
      with 10% sucrose. The results of these in vivo experiments revealed lower
      proportions of mutans streptococci after using all four types of toothpick, but
      the reduction was significant only after 2 days for the toothpicks impregnated
      with SnF2 and chlorhexidine (P< 0.05). On the sampling occasions 9 and 23 days
      after the treatment, the mutans streptococci were more or less back to baseline
      levels again. In saliva no significant differences in the number of mutans
      streptococci were found either within or between the four treatments. No
      significant differences were found regarding decline in the plaque-pH between the
      NaF-, SnF2-, chlorhexidine-, and non-impregnated toothpicks on any of the
      sampling occasions.

PMID- 9765010
TI  - Fluconazole versus nystatin in the treatment of oral candidosis.
AB  - The efficacy of oral fluconazole versus nystatin was evaluated as a treatment
      modality for oral candidosis. Of the included patients (n = 60), two-thirds
      presented with an erythematous candidosis, and the others showed clinical signs
      compatible with a pseudomembranous candidosis. Predisposing factors were
      xerostomia (n = 18), HIV (n = 5), immunosuppression in conjunction with organ
      transplantation (n = 10), and wearing of dentures (n = 14). For the remaining
      patients no specific predisposing factors were found. One patient who was treated
      with nystatin was excluded owing to nausea that was related to the antifungal
      treatment. After 7 days of treatment with fluconazole (50 mg/day), the affected
      oral mucosa, assessed by the investigator, was cured or showed considerable
      improvement in 87% of the patients (n = 30). The corresponding figure for the
      nystatin group (n = 30), rinsing with 1 mL 4 times a day for 21 days, was 80%.
      Following treatment with fluconazole, 20 of 22 patients with symptoms at the
      start (91%) reported improvement. The comparable figures for the nystatin group
      were 10 of 12 patients (83%). Half of the patients in the nystatin group reported
      inconvenience from taking the medication (mean value = 25.9) compared with 23% of
      the patients in the fluconazole group (mean value = 6.6). Eight patients in the
      fluconazole group and 12 patients in the nystatin group exhibited a relapse
      within 6 months. These differences were not found to be statistically
      significant. The patients in the fluconazole group reported less inconvenience
      from taking the medication, a finding that may have clinical implications for
      compliance.

PMID- 9765011
TI  - A descriptive study of how dentists view their profession and the doctor-patient
      relationship.
AB  - In this article we report on how 64 dentists working in a big city in southern
      Sweden view their profession. The dentists ranged in age from 30 to 70 years (as
      it was indicated in intervals of 10 years). Their professional experience ranged
      from 2 to 44 years (mean, 23 years). We collected their views on the ideal skills
      of a good dentist by means of a questionnaire. From this material we identified
      three categories: 1) interpersonal skills; 2) clinical skills; and 3) others,
      such as self-confidence, stress tolerance, and managerial and administrative
      skills. Next, they rated the relative importance of a number of listed attributes
      in dentistry in this order: contact with patients, communication skills, empathy,
      manual skills, and theory. Finally, they described a number of aspects of their
      profession. We conclude that the importance of interpersonal skills, as well as
      stress tolerance and administrative skills, is emphasized by experienced
      practitioners but that these skills are not focused on in the dental curriculum.

PMID- 9765012
TI  - Viscosity of whole saliva.
AB  - This study investigates within-subject variations and associations of salivary
      viscosities and flow rates in a test panel of healthy adults. After several
      practice sessions, unstimulated and stimulated whole saliva samples were
      collected 5 times daily (at 0800, 1100, 1400, 1700, and 2000 h) from 30
      university students. There was a significant within-subject variation in
      viscosity and flow rate of unstimulated saliva (P<0.001). Intra-item correlations
      were significantly different for salivary flow rates (r= 0.82 for unstimulated,
      r= 0.88 for stimulated, P< 0.001) and viscosity of unstimulated saliva (r= 0.54,
      P< 0.05), but viscosity of stimulated saliva was different in this respect. Our
      results indicate that there is a significant within-subject variation in
      viscosity of unstimulated saliva.

PMID- 9765013
TI  - A logistic regression model for analyzing the relation between dentists'
      attitudes, behavior, and knowledge in oral radiology.
AB  - The aim was to study the relation between risk attitude and knowledge in
      technical, patient-oriented, and organizationally related behavior within oral
      radiology. A questionnaire was mailed to 2000 randomly selected dentists listed
      in the register of the Swedish Dental Society, with a response rate of 69.3%.
      Regression analysis was used for analyzing the effects of the independent
      variables knowledge, risk attitude, continuing education in oral radiology,
      counties with specialists in oral radiology, type of practice, work experience,
      and sex on three categories of dependent variables: 1) technical behaviors: type
      of film, type of collimator, dose level, frequency of change of chemicals; 2)
      patient-oriented behaviors: use of patient protection barriers, strict
      indications for performing full-mouth X-ray examinations and bitewing radiography
      on new patients and recall patients; and 3) organizationally related behaviors:
      delegation of X-ray examinations to dental auxiliaries, influence on choice of
      collimator, influence on choice of film. Knowledge and education had strong
      direct effects for most of the dependent variables. The technical behaviors were
      mainly influenced by knowledge, education, and risk attitude, while
      organizationally related behaviors were influenced by type of practice and sex.
      The patient-oriented behaviors were influenced by a number of independent
      variables, such as education, type of practice, work experience, and sex. The
      present results indicate that both knowledge and the organizational context of
      dentists influence work.

PMID- 9765014
TI  - Nerve fibers immunoreactive to calcitonin gene-related peptide, substance P,
      neuropeptide Y, and dopamine beta-hydroxylase in innervated and denervated oral
      tissues in ferrets.
AB  - The effect of sensory and sympathetic denervation on the localization and
      distribution of nerve fibers immunoreactive (IR) to calcitonin gene-related
      peptide (CGRP), substance P (SP), neuropeptide Y (NPY), and dopamine beta
      hydroxylase (DBH) was studied in the dental pulp, periodontal ligament (PDL), and
      gingiva in ferrets. Unilateral axotomy was performed by resection of the inferior
      alveolar nerve (IAN) 10 days before the experiment (Group 1); sympathectomy, by
      unilateral removal of the cervical ganglion 5 days before the experiments (Group
      2). Immunohistochemistry was performed on free-floating sections by the avidin
      biotin-peroxidase technique. A considerably higher density of sensory fibers IR
      to CGRP and SP was found in the dental pulp than in PDL and gingiva. The majority
      of pulpal fibers were located in the walls of blood vessels. A subodontoblastic
      network of fibers IR to CGRP and SP was lacking in incisors and canines and was
      found only in the coronal pulp in premolars and molars. Sympathetic fibers were
      sparsely distributed in the pulp, and they were mainly confined to large vessels
      running centrally in the root pulp as well as the larger vessels in apical PDL
      and alveolar bone. Gingiva was well supplied with CGRP- and SP-IR nerves, and
      some NPY and DBH fibers were located in association with larger vessels. Round
      cell-like structures within the basal part of the epithelium were CGRP-IR.
      Axotomy induced a complete loss of CGRP- and SP-IR fibers in the anterior part of
      the jaws, whereas sympathectomy caused a reduction, but not a total loss, of NPY-
      and DBH-IR nerves. It is concluded that, except for some distributional
      differences, the oral tissues in the ferret have an abundant sensory innervation
      similar to that found in other species.

PMID- 9765015
TI  - Acceptance of dental care following early extractions under rectal sedation with
      diazepam in preschool children.
AB  - The aim of the study was to evaluate the effect of amnesia in preschool children
      on their later acceptance of dental care. Forty-six 4-6-year-old children, who
      between 2 and 4 years previously had had primary incisors extracted because of
      trauma, were reexamined for dental health and acceptance of dental care. The
      extractions had been performed under rectal sedation with diazepam (0.7 mg/kg
      body weight). Information about dental treatment and degree of cooperation during
      the intervening period was obtained from records at the referring clinic. The
      parents were interviewed about their child's experience of amnesia concerning the
      extractions, background variables, and experiences of dental care before the
      follow-up examination. Amnesia concerning the extractions was reported in 85% of
      the children. Twenty-nine percent had on some occasion exhibited behavior
      management problems (BMP) during the intervening period. Lack of amnesia was
      significantly associated with BMP (P< 0.002). Children without amnesia concerning
      the extractions tended to accept dental care less well at the reexamination.
      Parents were able to predict their child's acceptance of dental care at the
      follow-up with a significant degree of success (P= 0.02). In conclusion, amnesia
      in preschool children concerning extractions seems to be essential to facilitate
      positive acceptance of future dental care.

PMID- 9765016
TI  - Prolonged pacifier-sucking and use of a nursing bottle at night: possible risk
      factors for dental caries in children.
AB  - At the baseline of this cohort study we determined risk factors for colonization
      of oral lactobacilli and candida in a group of children (n = 166) whose mean age
      was 2.5 years. The results showed that pacifier-sucking and the use of a nursing
      bottle at night increase the occurrence of both salivary lactobacilli and
      candida. In the present study these children were followed for 2 years, and the
      progression of caries was recorded with particular reference to the etiologic
      factors measured before. The results of the logistic regression analysis showed
      prolonged pacifier-sucking (> or = 24 months) to be a significant risk factor for
      caries development in children, with a rather high relative risk (RR) of 3.5 (95%
      confidence interval (CI), 1.5-8.2; P= 0.003). Prolonged use of a nursing bottle
      at night (> or = 24 months) was also a risk factor, but less significant than
      pacifier-sucking (RR, 2.6; CI, 1.1-6.4; P= 0.03). On the grounds of this study we
      conclude that prolonged pacifier-sucking (> or = 2 years) and use of a nursing
      bottle at night are risk factors for dental caries in children.

PMID- 9765017
TI  - Validity of the Demirjian method for dental age estimation when applied to
      Norwegian children.
AB  - Dental age was studied in a sample of 261 Norwegian children by using the
      maturity standards of Demirjian & Goldstein (1976) to examine the applicability
      of these standards as a reference for overall dental maturity in a Norwegian
      population. The sample comprised 128 boys and 133 girls included in 'the Oslo
      Growth Material', from whom orthopantomograms (total, 783) had been
      longitudinally obtained, with intervals of about 3 years and covering 3 age spans
      (5.5-6.5 years, 8.5-9.5 years, and 11.5-12.5 years), each divided into 3 half
      year age groups. Reliability was analyzed by repeated assessments of 134 of the
      radiographs, and the overall mean difference between duplicate dental age
      determinations was 0.5 months for intra- and 1.8 months for inter-examiner
      comparisons. The Norwegian children were generally somewhat advanced in dental
      maturity compared with the French-Canadian reference sample. Among the boys the
      mean difference between dental age and chronologic age varied in the different
      age groups from 1.5 to 4.0 months. Among the girls the difference increased with
      age, varying from 0 to 3.5 months in the younger age groups (5.5 to 9.0 years)
      and from 4.5 to 7.5 months in the age groups 9.5 years and above. The variability
      in individual dental age was marked and increased with age. For the older age
      groups 95% of the individual age estimates were within +/-2 years of the real
      age. The applied standards appear to be adequate for studying dental age in
      groups of children from a Norwegian population. Given the considerable individual
      variation in dental maturity, estimation of chronologic age in individual
      children should be supplemented by other indicators of biologic maturity.

PMID- 9765019
TI  - The trichofolliculoma undergoes changes corresponding to the regressing normal
      hair follicle in its cycle.
AB  - The trichofolliculoma is a follicularly differentiated hamartoma, usually
      described as showing many vellus follicles, spreading from a central infundibular
      cyst. In spite of the well known regressive changes of normal hair follicles
      during catagen and telogen, the possibility of corresponding changes in the
      trichofolliculoma has not yet been discussed in the literature. By examining a
      total of 31 cases of trichofolliculoma it is demonstrated that this hamartoma
      undergoes an evolutionary process with great morphological changes, which can be
      attributed to the anagen, catagen, and telogen phase of the follicular cycle.

PMID- 9765018
TI  - Physicomechanical and cytotoxic properties of room temperature vulcanizing
      silicone prosthetic elastomers.
AB  - The physicomechanical and cytotoxic properties of two newly introduced room
      temperature vulcanizing (RTV) silicone prosthetic elastomers, Ideal and Silskin
      2000, were investigated. Another RTV silicone, Elastosil M3500, was also
      investigated as a potential facial material. The in vitro cytotoxicity was
      assessed with the agar diffusion test and mouse fibroblast cells (L929). The
      properties investigated were tensile strength, percentage elongation, modulus,
      tear strength, hardness, and color changes (deltaE*). The properties tested were
      selected because of their clinical significance in fabricating facial prostheses.
      The results indicate that Elastosil M3500 has a better combination of high tear
      strength, elongation at break, and low hardness than Ideal and Silskin 2000. All
      materials demonstrated a low cytotoxic profile. Elastosil M3500 warrants further
      attention with clinical trials.

PMID- 9765020
TI  - Folliculo-sebaceous cystic hamartoma is a trichofolliculoma at its very late
      stage.
AB  - Folliculo-sebaceous cystic hamartoma (FCH) was described as an entity recently
      and was defined as an adnexal hamartoma, showing above all an infundibular cystic
      structure linked to many sebaceous lobules. Differentiation toward the inferior
      segment of the hair follicle also occurs, although to a markedly lesser degree.
      Signs of regression and rest corresponding to the normal follicular cycle are
      often apparent in these follicular proliferations. Therefore so-called FCH has
      much in common with the newly described late stage of trichofolliculoma, which
      also exhibits an infundibular cyst and sebaceous and follicular differentiation
      with various signs of catagen and telogen. Comparing our 8 cases of FCH and 31
      cases of trichofolliculoma, we came to the conclusion that FCH is the very late
      stage of trichofolliculoma. This stage could be characterized by a nearly
      complete regression of the transient follicular epithelium, whereas concurrent
      growth and maturation of sebaceous elements appear.

PMID- 9765021
TI  - Cathepsin D expression in skin metastasis of breast cancer.
AB  - Cathepsin D, an aspartic proteinase, correlates with invasion and metastasis in
      breast cancer and with poor prognosis. In the present study, we examined the
      immunohistological expression of cathepsin D in both primary (5 cases) and skin
      metastatic breast cancers (13 cases) and compared it to those in gastric (2
      cases) and lung (4 cases), and primary eccrine cancers (3 cases). All breast and
      gastric cancers were adenocarcinomas. The 2 gastric cancers were poorly
      differentiated, while the 4 lung cancers consisted of 2 poorly differentiated
      adenocarcinomas, 1 poorly differentiated large cell carcinoma, and 1 moderately
      to poorly differentiated squamous cell carcinoma. We also surveyed the
      immunohistological distribution of cathepsin B, carcinoembryonic antigen, gross
      cystic disease fluid protein-15, c-erbB-2, and estrogen receptor. In almost all
      breast cancer samples, the cancer cells demonstrated strong expression of
      cathepsin D in the cytoplasm, but weak staining patterns with other antibodies.
      Gastric and lung cancer cells did not respond with cathepsin D (except one
      metastatic lung cancer) or the other immunohistological markers. Since cathepsin
      D is strongly expressed in primary and metastatic lesions of breast cancer,
      cathepsin D could be useful as an adjunct to a panel of immunohistochemical
      stains in determining the primary site of origin of metastatic cancer in the
      skin.

PMID- 9765022
TI  - Cutaneous Langerhans cell histiocytosis of the genitalia in the elderly: a report
      of three cases.
AB  - Langerhans cell histiocytosis (LCH) is a disease with a broad spectrum of
      clinical presentations. All of the variants have in common the proliferation of
      cells which are morphologically, biochemically, and immunophenotypically
      indistinguishable from Langerhans cells. A retrospective study of three elderly
      patients revealed the unique presentation of cutaneous Langerhans cell
      histiocytosis limited to the genitalia. These cases produced a diagnostic
      challenge because of their unusual clinical presentation and their morphological
      similarity to certain other entities, including extramammary Paget's disease and
      malignant melanoma, which may also show S-100-positive atypical cells. All three
      cases showed infiltrates of histiocytic-appearing cells with folded nuclei and
      moderate amounts of cytoplasm which involved the epidermis, dermis, or both.
      Immunoperoxidase studies using antibody to S-100, CD1a and CD68 in each case
      showed positive staining.

PMID- 9765023
TI  - Numbers and differentiation status of melanocytes in idiopathic guttate
      hypomelanosis.
AB  - The etiology and pathogenesis of idiopathic guttate hypomelanosis (IGH) are
      largely unknown. To investigate whether the pathologic alteration in IGH involves
      changes in melanocytic differentiation, cell number, or both, we studied nine
      lesions of IGH by immunoperoxidase, using monoclonal antibodies against the KIT
      receptor and a panel of melanocyte differentiation antigens (tyrosinase-related
      protein-1, tyrosinase, and gp100/pme117). In each case, compared with grossly
      normal non-lesional skin, IGH lesions showed markedly reduced numbers both of
      KIT+ cells and of cells expressing melanocyte differentiation antigens (p <
      0.0001). Double immunofluorescence labeling of lesions revealed only scattered
      cells with a less-differentiated phenotype, i.e. cells positive for KIT but
      having low or undetectable TRP-1. These results indicate that the pathogenesis of
      IGH involves an absolute decrease in the number of melanocytes; a block in
      melanocyte differentiation does not appear to be a major component of the
      process.

PMID- 9765024
TI  - Hermansky-Pudlak syndrome: report of a case with histological,
      immunohistochemical and ultrastructural findings.
AB  - We report a 38-year-old female of Puerto Rican descent with Hermansky-Pudlak
      syndrome and decreased levels of von Willebrand factor. Histologic and
      ultrastructural findings of non-sunexposed skin showed melanocytes with short
      dendritic processes and decreased numbers of melanosomes. Ultrastructural
      examination of platelets revealed greatly reduced numbers of delta granules.
      Recognition of this syndrome is important because skin neoplasms, ceroid
      deposition and hemorrhagic manifestations can be causes of morbidity and of
      potential death in patients affected with this syndrome.

PMID- 9765025
TI  - Myxoid dermatofibrosarcoma protuberans: morphological, ultrastructural and
      immunohistochemical features.
AB  - Two uncommon cases of dermatofibrosarcoma protuberans with prominent myxoid
      changes are presented. The tumors appeared as large multinodular cutaneous
      plaques that arose at the sites of excision of previous tumors some years
      earlier. In addition to limited fibrous storiform features, focally observed in
      deep and peripheral portions of the tumors, a diffuse myxoid pattern could be
      observed. The latter consisted of homogeneous areas of rare, stellate or spindle
      shaped cells, haphazardly scattered in abundant myxoid matrix. Cells of myxoid
      neoplastic tissue showed mainly a positive immunoreaction for fibrohistocytic
      markers and the absence either of muscular, neural or human progenitor cell
      antigens. Mitotic figures were fewer and cell proliferation rates were lower in
      myxoid as compared to those of typical dermatofibrosarcoma protuberans used as a
      control. The ultrastructural examination of myxoid areas revealed a prevalent
      fibroblast-like cell population showing dilated cytoplasmic vesicles, sometimes
      containing glycosaminoglycans-like substances. The extent of myxoid changes
      together with the characteristic morphological, ultrastructural and
      immunohistochemical features confirm that myxoid dermatofibrosarcoma protuberans
      is a distinct variant of this fibrohistiocytic tumor to be considered in the
      differential diagnosis among myxoid tumors of the skin.

PMID- 9765026
TI  - Subcutaneous panniculitis-like T-cell lymphoma: further evidence for a distinct
      neoplasm originating from large granular lymphocytes of T/NK phenotype.
AB  - We report the case of a 20 year-old caucasian woman who presented a primary
      subcutaneous panniculitis-like T-cell lymphoma (SPTCL) as an invasive tumor of
      the chest wall. Herein, the neoplastic cells were found to express a CD3+CD8+
      phenotype but also displayed variably the natural killer (NK)-associated antigens
      CD56 and CD57 as well as granzyme B. On cytological examination, these cells
      showed a large granular lymphocyte (LGL)-like morphology with presence of
      azurophilic granules in their cytoplasm. Electron dense and membrane bound
      granules like those found in cytotoxic T lymphocytes (CTL) were also demonstrated
      by electron microscopy. Neither rearrangement of the T-cell receptor subunits nor
      Epstein-Barr virus (EBV) genome was observed at the molecular level. The LGL-like
      features of the neoplastic cells found in this case and the presence of NK
      associated antigens provide additional support to the cytotoxic derivation of
      most SPTCL.

PMID- 9765027
TI  - DNA/genetic vaccination (minireview).
AB  - An important new approach to vaccination is plasmid DNA injection in vivo that
      can elicit an immune response against protein(s) encoded. Antigen that is
      expressed from the in vivo transfected cells induces both humoral and cellular
      immune response. DNA immunization is generally applicable for a wide range of
      proteins. It can provide an organism with immunity against viruses, bacteria,
      parasites, and tumors. DNA vaccines can overcome the disadvantages of vaccines
      presently used as well as provide various new vaccines that are currently not
      available. This minireview provides an overview of evaluated DNA vaccine
      candidates against infectious agents and certain cancers.

PMID- 9765028
TI  - Effect of plasmid DNA on immunogenicity of HBsAg-anti-HBs complex.
AB  - Hepatitis B surface antigen (HBsAg) complexed with anti-HBs is more immunogenic
      than HBsAg alone in mice. This complex is usually used with alum as an adjuvant,
      which can enhance humoral response but inhibits cell-mediated immune responses.
      To improve the immunogenicity of HBsAg-anti-HBs, we immunized mice with a
      combination of this immunogenic complex and pCMVHBs, a plasmid encoding HBsAg, or
      the vector pCMV. Both plasmids enhanced the anti-HBs response induced by the
      immunogenic complex. We found 20 microg of plasmid or vector enhanced the anti
      HBs response in all mice, whereas 1 microg was less effective. Splenocytes from
      different immunized groups were stimulated with HBsAg in vitro, and the highest
      level of IL-2 detected in the supernatant was found in mice immunized with HBsAg
      anti-HBs plus pCMVHBs. A plasmid (pcDNA3c191) encoding core protein of hepatitis
      C virus (HCV) was used as an adjuvant to the immunogenic complex. A preliminary
      result showed that pcDNA3c191 not only enhanced the immunogenicity of HBsAg-anti
      HBs, but also induced anti-HCV core antibodies. Immunization using a plasmid DNA
      encoding one viral antigen in combination with antigen and antibody complex of
      another microbial origin could be a new approach to the development of
      multivalent vaccines.

PMID- 9765029
TI  - The capacity of a combined liposomal hepatitis B and C vaccine to stimulate
      humoral and cellular responses in mice.
AB  - Combined hepatitis B surface antigen and hepatitis C antigen were encapsulated
      into 1, 2, and 5 microm discrete liposomes and then lyophilized. Groups of
      adolescent CD-1 mice were given a single 0.3 mL oral dose of these liposomes
      containing 50 microg/mL hepatitis B surface antigen and hepatitis C antigen, 50
      microg/mL of the same antigens or liposomes alone. Animals in each group were
      sacrificed every 2 weeks for 10 weeks and the humoral response investigated by
      enzyme-linked immunosorbent assay (ELISA) and the cellular response by splenic
      lymphocyte proliferation to 10 microg of either antigen. Seroconversion to both
      antigens in the mice receiving liposomal antigens occurred in 87.5% of animals
      sacrificed at 4 weeks and later. One animal (12.5%) receiving antigen alone
      seroconverted to hepatitis B virus at 6 weeks, but all animals receiving
      liposomes alone remained negative. Proliferation indexes (PI) greater than 3 were
      observed in all animals receiving liposomal antigens, with the greatest response
      seen at 10 weeks. PI was less than 2 for all animals in the other two groups.
      Thus, a single oral dose of liposomes of three sizes containing both hepatitis B
      and C antigens given to mice resulted in rapid seroconversion and a progressive
      robust cellular immune response, whereas the antigens alone or liposomes without
      antigen did not.

PMID- 9765030
TI  - Induction of immunity in the respiratory tract and protection from bovine
      herpesvirus type 1 infection by different routes of immunization with recombinant
      adenovirus.
AB  - To investigate the capability of different routes of immunization with
      replication-competent recombinant adenovirus to induce antigen-specific antibody
      responses, we immunized cotton rats with a human adenovirus type 5 (HAd5) vector
      expressing the glycoprotein D (gD) of bovine herpesvirus type 1 (BHV-1) (gD-dE3).
      Different routes of mucosal and systemic immunization (intraduodenal-oral,
      intraduodenal, intranasal and intradermal) with gD-dE3 stimulated similar levels
      of gD-specific IgG in the serum of cotton rats. However, intranasal (i.n.)
      immunization stimulated higher levels of gD-specific IgA in the lung and nasal
      washes, and higher frequency of gD-specific antibody secreting cells in the lung
      than did the intradermal immunization. Higher levels of antibody in the
      respiratory tract following i.n. immunization correlated with better protection
      of the lungs against i.n. BHV-1 challenge. Intraduodenal-oral immunization
      induced more gD-specific antibodies in the respiratory tract than intraduodenal
      immunization alone. Adenovirus dissemination to most organs tested was evident
      following each route of immunization, which is important to consider when
      studying the mechanism of induction of immunity by recombinant adenoviruses.

PMID- 9765031
TI  - Point mutation of a rubella virus E1 protein T-cell epitope by substitution of
      single amino acid reversed the restrictive HLA-DR polymorphism: a possible
      mechanism maintaining HLA polymorphism.
AB  - The influence of single amino acid substitutions within a rubella E1 protein T
      cell epitope, E1(273-284) on T-cell recognition was studied. Substitutions of an
      uncharged amino acid A for an E or for a T and substitution of a T for S were
      found to not significantly reduce the T-cell responses. However, substitution of
      a charged residue such as E for hydrophobic residues (I, V, or W); D for Q; or a
      relatively larger size amino acid for polar residues completely abolished the
      cytotoxicities mediated by E1(273-284)-specific T-cell clone. A set of single
      amino acid-substituted peptide analogs of E1(273-284) not eliciting cytotoxicity
      of the T-cell clone was used to test the influence of point mutation of the
      epitope on HLA DR restrictions. A panel of B-cell lines with different DR4
      subtypes was used as targets in cytotoxicity assays to determine the restrictive
      HLA molecules. Results showed that modification of the T-cell epitope by point
      mutation could reverse the HLA DR restriction from one allele to other alleles. A
      model based on these results has been proposed to explain the mechanism balancing
      major histocompatibility complex (MHC) polymorphism in outbred populations.

PMID- 9765032
TI  - Hantavirus seropositivity in Israeli patients with renal failure.
AB  - The hantavirus is known to cause hemorraghic fever with renal syndrome (HFRS),
      which is widely spread in Europe and Asia. Several reports have shown an
      association of hantavirus antibody titers and the occurrence of renal
      dysfunction. From these observations, it appears that the virus is widely
      distributed, and different strains prevail in various areas. In the present work
      we studied 81 patients with end-stage renal-failure under hemodialysis (HD)
      treatment, 55 with mild to moderate renal failure, and 50 healthy subjects for
      the presence of antibodies to Hantaan and Puumala viruses. We found that 12.3% of
      the hemodialysis patients and 9% of the mild to moderate renal failure patients
      had elevated IgG anti-body titers to Puumala virus compared with 2% of the
      controls. IgM antibodies to Puumala virus was principally elevated in patient
      with chronic renal failure (CRF) not on hemodialysis (14.5%) compared with the
      hemodialyzed (1.2%) and controls (0%) subjects. Hantaan virus IgG antibodies were
      detected in 3.7% of the HD patients, 5.5% of the CRF not on HD, and in none of
      the controls. IgM Hantaan antibodies were found only in the non-HD renal failure
      patients. None of the sera were found to contain antibodies to phospholipids or
      single-stranded DNA. These results emphasize the widespread nature of infection
      with hantaviruses and imply that elaborate testing for these serologies should be
      performed, especially in patients with unexplained renal failure.

PMID- 9765033
TI  - Assessment of curve progression in idiopathic scoliosis.
AB  - In a 5-year prospective study on idiopathic scoliosis, an attempt was made to
      elucidate the natural history of the disease and to determine which factors
      contribute to curve progression. A total of 85,622 children were examined for
      scoliosis in a prospective school screening study carried out in northwestern and
      central Greece. Curve progression was studied in 839 of the 1,436 children with
      idiopathic scoliosis of at least 10 degrees detected from the school screening
      program. Each child was followed clinically and roentgenographically for one to
      four follow-up visits for a mean of 3.2 years. Progression of the scoliotic curve
      was recorded in 14.7% of the children. Spontaneous improvement of at least 5
      degrees was observed in 27.4% of them, with 80 children (9.5%) demonstrating
      complete spontaneous resolution. Eighteen percent of the patients remained
      stable, while the remaining patients demonstrated nonsignificant changes of less
      than 5 degrees in curve magnitude. A strong association was observed between the
      incidence of progression and the sex of the child, curve pattern, maturity, and
      to a lesser extent age and curve magnitude. More specifically, the following were
      associated with a high risk of curve progression: sex (girls); curve pattern
      (right thoracic and double curves in girls, and right lumbar curves in boys);
      maturity (girls before the onset of menses); age (time of pubertal growth spurt);
      and curve magnitude (> or = 30 degrees). On the other hand, left thoracic curves
      showed a weak tendency for progression. In conclusion, the findings of the
      present study strongly suggest that only a small percentage of scoliotic curves
      will undergo progression. The pattern of the curve according to curve direction
      and sex of the child was found to be a key indicator of which curves will
      progress.

PMID- 9765034
TI  - Radiation protection of the ovaries in young scoliosis patients.
AB  - Concerns in clinical practice arose over the amount of ovarian irradiation
      received from X-ray examinations in females with scoliosis. This study was
      instigated to assess the adequacy of ovarian protection in this young and
      genetically vulnerable group of patients. A total of 283 plain films in 20
      patients with scoliosis were reviewed. If the area immediately adjacent to the
      medial wall of the acetabulum was clearly seen, then this was taken as indicative
      of ovarian irradiation. In a separate study, the radiation dose in the centre of
      the X-ray field on the surface of a tissue-equivalent anthropomorphic phantom was
      measured using thermoluminescent dosimeters. Standard conditions for scoliosis X
      ray examination were used. The average age of patients was 21.5 years. The mean
      number of single X-ray exposures per patient was 14.1 over a mean of 44 months.
      The mean measured entrance dose to the skin in the 20 patients was 0.08 mGy
      (equivalent dose = 0.08 mSv). The mean percentage of examinations without lead
      protection was 18% per patient (range 0-40%). This would have resulted in a mean
      equivalent dose to the surface of the abdomen of 0.1 mSv per year per patient
      from the unprotected examinations. The maximum dose received in 1 year was 0.6
      mSv. The maximum dose to the unprotected ovary was estimated to be 0.05 mSv from
      a single examination. The mean total cumulative ovarian dose was calculated as
      180 microSv per patient (range 45-355 microSv) over the time period studied. The
      findings of this study indicate that ovarian protection should be improved.
      Reasons for this and suggestions for improvement are discussed.

PMID- 9765035
TI  - Volumetric determination of normal and scoliotic vertebral bodies.
AB  - A new method is presented for stereological evaluation of the volume of the
      vertebral body in vivo. The height of the vertebral body is measured at three
      standardised points on an anteroposterior radiograph and at two other points on a
      lateral one. The area of the body is also measured using a special grid
      superimposed on a CT scan from the middle part of the vertebra. The volume of the
      vertebral body is then calculated using Cavalieri's principle for irregular
      objects: V = delta a x H, where V is the volume of the vertebral body, delta a is
      the mean cross-section surface area on the CT scan and H is the mean of the
      heights at the five points on the radiographs, computed as mean weighted
      circumferential height. The volume of one normal and one scoliotic vertebra was
      evaluated in vitro using this formula. The obtained values were compared with the
      values derived from serial CT scans of the two vertebrae. The results showed that
      the volume of the normal vertebra measured with our new method was 15.9 cm3 and
      measured with serial CT scans using the same grid it was 15.07 cm3. For the
      scoliotic vertebra the values were 17.6 and 17.3 cm3, respectively. The degree of
      accuracy of the measurements with the presented method as compared with the
      serial CT method was 95% for the normal and 98.5% for the scoliotic vertebra. To
      prove the clinical applicability of the method, the heights of the apical and of
      the upper and the lower end vertebrae of the curve and the volume of the apical
      vertebrae were evaluated in eight scoliotic girls (nine curves) before and 3
      years after spinal instrumentation and posterior fusion. The results showed that
      the mean circumferential height of the three vertebrae had increased
      significantly at the last follow-up. The volume of the apical vertebra had also
      increased, but the difference was not significant. It is concluded that the
      described method is easy to apply and has satisfactory accuracy for in vivo
      longitudinal studies of the volume of the vertebral body on radiographs and CT
      scans.

PMID- 9765036
TI  - Paraspinal muscle fibre type alterations associated with scoliosis: an old
      problem revisited with new evidence.
AB  - To establish the extent to which the paraspinal muscles are affected in
      idiopathic scoliosis, samples from patients must be compared with controls of a
      similar gender and age. To date, insufficient control data has been available for
      these purposes. The aim of this study was to re-dress this tissue, in order to
      identify whether one side of the apex of the scoliotic curve showed greater
      muscular abnormalities than the other. Bilateral samples of the paraspinal
      muscles were obtained during surgery from 14 female scoliosis patients, at the
      apex of the scoliotic curve at T9-T11. Percutaneous muscle biopsy samples were
      obtained from nine female volunteers, on the left side of the spine at T10.
      Samples were prepared for routine histochemistry for the identification of muscle
      fibre types. Fibre size was measured using computerised image analysis. Compared
      with control muscle, there was a significantly lower proportion of type I (slow
      twitch oxidative) fibres in the muscle on the concave side of the scoliotic
      curve, but no difference on the convex side. The proportion of type IIB (fast
      twitch, glycolytic) fibres was higher on both sides of the curve compared with
      controls, with the effect being significantly more marked on the concave side.
      The percentage of type IIA (slow-twitch, oxidative-glycolytic) fibres did not
      differ between the groups, and neither did fibre size (although there was a
      tendency for the controls to have larger type IIA fibres than the patients).
      Collectively, the differences in fibre type size and distribution meant that on
      the concave side the relative area of the muscle occupied by type I fibres was
      smaller, and on both sides of the curve the relative area occupied by type IIB
      fibres was greater and by type IIA fibres smaller, in comparison with controls.
      In scoliosis, the spinal musculature is most affected on the concave side of the
      curve's apex. The muscle adopts a 'faster', or more 'glycolytic' profile, which
      would be consistent with a reduced low-level tonic activity of the muscle,
      perhaps consequent to a local change in activity on this side of the spine
      following progression of the curve. Less marked changes, in the same direction,
      are also evident on the convex side; these may be the result of general disuse of
      the paraspinal muscles associated with the spinal deformity.

PMID- 9765037
TI  - Preoperative evaluation of activity and function in patients with paralytic
      scoliosis.
AB  - Preoperative evaluation of patients with paralytic scoliosis should take into
      account the consequences of surgery on the every day life of the patient.
      However, the parameters that are customarily used in these operations relate only
      to very narrow measures such as the angle of scoliosis or kyphosis. The aim of
      this study was to introduce a set of instruments appropriate for measuring both
      function and activities in paralytic scoliosis patients. The study took as its
      starting point the WHO International Classification of Impairments, Disabilities
      and Handicaps (ICIDH), in which an activity is described at the level of the
      individual and function at the level of the organ. A consecutive series of 100
      paralytic scoliosis patients with 18 different diagnoses were evaluated
      preoperatively with a set of instruments that had been specially developed at
      Linkoping hospital, in which the variables are classified according to the system
      used in the ICIDH. The set of instruments included general information and
      evaluation of activities and function--sitting, balance, weight distribution to
      sitting surface, angle of scoliosis, reaching, pain estimation, activities of
      daily living (ADL) Barthel and ADL Klein and Bell, care given, time spent
      resting, and seating supports). The results showed that patients with paralytic
      scoliosis constitute a heterogeneous group in activities and function. Even when
      the patients were grouped into four subgroups according to the Scoliosis Research
      Society Classification, they remained very heterogeneous. However, reaching,
      Klein and Bell Activities of Daily Living and pain could only evaluate patients
      who could understand verbal instructions. In those who could not, assessment
      relied more heavily on measures of function and level of dependence. It was
      concluded that the choice of assessment must be guided by the patient's ability
      to understand verbal instructions irrespective of his/her disorder. It is
      important to use the three levels--impairments, disabilities and handicaps-- in
      order to focus on the different outcomes in the two groups with respect to the
      patient's total situation.

PMID- 9765038
TI  - Plate fixation adds stability to two-level anterior fusion in the cervical spine:
      a randomized study using radiostereometry.
AB  - This study evaluated whether addition of a cervical spine locking plate (CSLP) in
      two-level disc fusions improved the postoperative stability and reduced the time
      to healing. Radiostereometric analysis was used to obtain precise recordings of
      the three-dimensional motion between the fused vertebrae. Eighteen consecutive
      patients were operated on with excision of two adjacent cervical discs and
      anterior horseshoe grafting with autologous bone (Smith Robinson technique). Nine
      patients were randomized to stabilization with autologous bone grafting and CSLP
      plate fixation and nine patients to grafting without fixation. Clinical symptoms
      in terms of pain in the neck and the arm were analysed preoperatively and after 1
      year using a visual analogue scale (VAS). The patients operated without a plate
      displayed increased rotations around the transverse axis, corresponding to the
      development of a kyphosis [mean value no plate/plate 14.4 degrees/0.8 degrees
      (repeated measure ANOVA: P < 0.01)]. The mean compression was 3.2 mm larger in
      patients operated without a plate (repeated measure ANOVA: P < 0.01). Patients
      operated without a plate had more arm pain at the 1-year follow up (P < 0.05,
      Mann-Whitney U test). The VAS score for neck pain did not differ significantly
      between the two groups. Plate fixation could not be demonstrated to increase the
      healing rate, promote more rapid fusion or influence the frequency of graft
      complications.

PMID- 9765039
TI  - Occipito-cervical fusion using posterior titanium plates.
AB  - Occipito-cervical fusion may be indicated for instability of the occipito
      cervical junction or atlanto-axial spine secondary to a wide spectrum of
      pathology. Many techniques exist to stabilize the spine until fusion is achieved.
      Recent reports of plate fixation have been favorable. In this study we set out to
      determine the effectiveness and advantages of titanium plate fixation when used
      to stabilize the occipito-cervical junction. Thirteen patients with occipito
      cervical instability or atlanto-axial instability underwent occipito-cervical
      fusion using posterior titanium plates. The plates were contoured to the occipito
      cervical junction and fastened to the skull with screws, and to the spine with
      lateral mass screws. The patients were followed prospectively clinically and
      radiographically to a minimum of 24 months. Outcome parameters included peri
      operative morbidity and complications, hardware integrity, spinal alignment,
      fusion, and neurological status. Twelve of thirteen patients went on to solid
      fusion radiologically and clinically, and recovered or improved from their
      myelopathy. One patient did not. Three patients had radiographic evidence that
      two screws were loose and one screw was broken. There were no instances of plate
      breakage. We conclude that titanium plate fixation of the occipito-cervical
      junction is versatile and stable. The plates maintain axial correction and allow
      for future MR imaging.

PMID- 9765040
TI  - The stability of bone screws in the os sacrum.
AB  - A variety of points of insertion and implantation techniques are recommended for
      inserting screws into the os sacrum. On the basis of 16 complete human sacrum
      specimens the following axial pull-out tests were performed: 1. Insertion of
      convergent measuring screws, 6.0 mm and 7.0 mm in outside diameter respectively,
      into the body of vertebra S1 using a monocortical and bicortical technique
      respectively with perforation of the ventral cortex. 2. Insertion of divergent
      screws into the ala sacralis at the level of S1 with 6-mm and 7 mm screws
      respectively, using a monocortical technique without perforation of the ventral
      cortex. 3. Insertion of convergent 6-mm screws into the body of vertebra S2 using
      a monocortical and bicortical technique respectively with perforation of the
      ventral cortex. The highest axial pull-out force was reached using convergent 6
      mm screws inserted into the body of vertebra S1 using the bicortical technique
      with perforation of the ventral cortex (2392.4 N). The use of a 7.0-mm screw in
      the same implantation technique did not result in higher pull-out forces (2274.7
      N). The monocortical technique reached a pull-out force of 1657.53 N with a 6-mm
      screw and 1505.64 N with a 7-mm screw. Convergent insertion of 6-mm screws into
      the body of S2 resulted in pull-out forces of 537.02 N using a bicortical and
      only 297.71 N using a monocortical technique. Divergent insertion of screws into
      the ala sacralis reached a maximal pull-out force of 495.47 N using 6-mm screws
      and 449.79 N using 7-mm screws. These data resulted from a monocortical
      implantation technique without perforation of the ventral cortex of the ala
      sacralis. The results of the present biomechanical study show that convergent
      bicortical implantation in the body of S1 is the most stable technique for screw
      fixation in the sacrum. The use of 7-mm rather than 6-mm screws did not lead to
      increased primary stability. Anatomic studies have shown that a safe area exists
      in the region of the ventral promontory, so this implantation technique appears
      to be unobjectionable.

PMID- 9765041
TI  - Functional outcome after posterolateral spinal fusion using pedicle screws:
      comparison between primary and salvage procedure.
AB  - Lumbar spinal fusion is a commonly performed surgical procedure, yet both the
      indications for its performance and its results remain controversial. It is
      generally believed that apart from situations where obvious measurable
      instability exists, a repeat surgical procedure such as spinal fusion does not
      improve the functional outcome in more than an average of 50% of cases. The aim
      of this study was to analyse functional outcome after posterolateral lumbar or
      lumbosacral spinal fusion, comparing primary and salvage procedures. It was
      designed as a prospective case/referent study with a 2-year follow-up. A total of
      39 patients underwent a short posterior fusion with Cotrel-Dubousset (CD) pedicle
      screw fixation after earlier surgery of the lumbar spine. Two patients were
      erroneously omitted from the study at the index, so 37 patients were included in
      the salvage group. In the same period, 69 patients underwent lumbar fusion with
      pedicle screw fixation (CD) as primary surgery (referent group). Functional
      outcome was assessed by means of the Dallas Pain Questionnaire preoperatively and
      1 and 2 years postoperatively. Fusion rates were determined by ordinary X-ray
      evaluation by two independent observers. Patients who had undergone previous
      spinal surgery had a significant improvement in functional outcome in terms of
      daily activity, work and leisure-time activities and anxiety/depression. With
      regard to social functioning, a significantly inferior outcome was found after
      the salvage procedure. The return-to-work rates at 2 years after surgery were 50%
      in the salvage group and 53% in the referent group. There was a significant
      correlation between radiological evaluation of the fusion mass and the functional
      outcome. The fusion rate was 76% in the salvage group and 72% in the referent
      group. This study demonstrates that a posterolateral spinal fusion can be
      effectively used as a salvage procedure. The functional and radiological outcome
      of the patients with revision surgery did not differ from those of the group of
      patients who underwent primary surgery. There was, however a clear indication of
      inferior social functioning after revision surgery.

PMID- 9765042
TI  - Value of quantitative radionuclide bone scanning in the diagnosis of sacroiliac
      joint syndrome in 32 patients with low back pain.
AB  - A prospective study was performed to compare the results of quantitative
      radionuclide bone scanning with those of sacroiliac joint anesthetic block in
      patients with unilateral low back pain. Thirty-four subjects, forming the control
      group, underwent quantitative radionuclide bone scanning of the sacroiliac
      joints. The normal values in sacroiliac uptake difference were taken to be
      between -1.7% and +6.2%. Thirty-two patients with chronic unilateral low back
      pain underwent sacroiliac bone scanning and sacroiliac joint block. Six of the
      seven patients with increased uptake > 6.2% on the painful side had at least 75%
      pain reduction in response to the block. The sensitivity, specificity, and
      positive and negative predictive values of the quantitative bone scanning in the
      unilateral mechanical sacroiliac joint syndrome were 46.1%, 89.5%, 85.7%, and
      72%, respectively.

PMID- 9765043
TI  - Graded thoracolumbar spinal injuries: development of multidirectional
      instability.
AB  - Injuries of the thoracolumbar spine are serious, disabling, and costly to
      society. These injuries vary from mild ligament tears to severe bony fractures.
      Increased range of motion (ROM) and neutral zone (NZ) have been suggested as
      indicators of the resulting clinical instability. The purpose of the present
      study was to investigate the relative sensitivities and merits of the ROM and NZ
      in relation to spinal injuries of the thoracolumbar junction. A graded spinal
      trauma experiment was designed, in which the threshold of injury and injury
      progression were examined. Ten thoracolumbar human spine specimens (T11-L1) were
      traumatized using a high-speed incremental trauma model. The ROM and NZ, which
      indicate altered mechanical properties, were determined for three physiological
      motions: flexion/extension (FE), lateral bending (LB), and axial rotation (AR).
      The injury threshold was found to be 84 J (or 84 Nm) by examining both ROM and NZ
      for all motion types (P < 0.05), but the NZ was more sensitive. At the injury
      threshold, the NZ showed an overall average increase of 566% above that of the
      intact, while the equivalent increase in the ROM was only 94%. The NZ was also a
      more sensitive parameter documenting the progression of the injury beyond the
      injury threshold. After the maximum trauma of 137 J, the NZs for the three
      motions (FE, LB, and AR) increased by 700%, 1700%, and 3000% above their
      respective intact values. Corresponding increases in the ROM were much smaller:
      115%, 184%, and 425% respectively. Direct extrapolation of the in vitro
      experimental findings to the clinical situation, as always, should be done with
      care. Our findings, however, suggest that the ROM, as measured from functional
      radiographs of a traumatized patient, may underestimate the true injury to the
      spinal column.

PMID- 9765044
TI  - Chronic recurrent multifocal osteomyelitis causing spinal cord compression.
AB  - Chronic recurrent multifocal osteomyelitis (CRMO) is a very rare condition of
      unknown etiology and most commonly occurs during childhood or adolescence. The
      purpose of this paper is to present a case of CRMO in a vertebral location with
      severe kyphosis, spinal cord compression, and neurological dysfunction requiring
      anterior decompression and fusion. After 12 weeks, the patient was physically
      able to return to school. At 2-year follow-up, neurological and functional
      outcomes are fair. Magnetic resonance imaging shows good restoration of the
      sagittal spine alignment despite residual mild kyphosis, and restoration of a
      normal sagittal diameter of the spinal canal.

PMID- 9765045
TI  - Intraosseous lipomata of adjacent vertebral bodies.
AB  - Osseous lipomata of vertebral bodies are rare. We present a very unusual case
      where adjacent vertebrae are involved and the plain radiographic and
      scintigraphic appearances gave cause for some concern. The findings on plain
      films, scintigraphy, computed tomography and magnetic resonance imaging are
      discussed.

PMID- 9765046
TI  - Three-level thoracic disc herniation: case report and review of the literature
      (P. G. Korovessis et al., ESJ 1997, Vol. 6, p. 74-76)

PMID- 9765047
TI  - Spectral analysis methods for neurological signals.
AB  - This paper reviews some novel spectral analysis techniques that are useful for
      neurological signals in general and EEG signals in particular. First, some
      drawbacks and limitations of the commonly used Fast Fourier transforms (FFTs) are
      presented, and then alternative algorithms are outlined. An auto-regressive (AR)
      modeling based spectral estimation procedure is presented to overcome the
      problems of lower resolution and 'leakage' effects inherent in the FFT algorithm.
      For signals which are transient in nature or rapidly time-varying, two
      alternative algorithms are presented. The first is an adaptive AR parameter
      estimation algorithm and the second is a wavelet based time-frequency
      representation algorithm. Finally, a Spectral Distance measure and the Itakura
      distance measure are presented to quantify the differences between the spectra of
      two signals in a succinct manner. The application and performance of all the
      algorithms is illustrated using electroencephalograms (EEGs) recorded in animals
      during hypoxic asphyxic injury to brain.

PMID- 9765048
TI  - The Fourier analysis of biological transients.
AB  - With modern computing technology the digital implementation of the Fourier
      transform is widely available, mostly in the form of the fast Fourier transform
      (FFT). Although the FFT has become almost synonymous with the Fourier transform,
      it is a fast numerical technique for computing the discrete Fourier transform
      (DFT) of a finite sequence of sampled data. The DFT is not directly equivalent to
      the continuous Fourier transform of the underlying biological signal, which
      becomes important when analyzing biological transients. Although this distinction
      is well known by some, for many it leads to confusion in how to interpret the FFT
      of biological data, and in how to precondition data so as to yield a more
      accurate Fourier transform using the FFT. We review here the fundamentals of
      Fourier analysis with emphasis on the analysis of transient signals. As an
      example of a transient, we consider the human saccade to illustrate the pitfalls
      and advantages of various Fourier analyses.

PMID- 9765049
TI  - A comparison of fast Fourier transform (FFT) and autoregressive (AR) spectral
      estimation techniques for the analysis of tremor data.
AB  - This review outlines the theory of spectral estimation techniques based on the
      fast Fourier transform (FFT) and autoregressive (AR) model and their application
      to the analysis of human tremor data. Two FFT-based spectral estimation
      techniques are presented, the Blackman-Tukey and periodogram methods. Factors
      that influence the quality of spectral estimates are discussed including the
      choice of windowing function. The theory of parametric modelling is introduced
      and AR modelling identified as the technique best suited to the analysis of
      tremor data. The processes of parameter estimation and model order selection are
      described. The theory of AR spectral estimation is outlined and differences
      between the AR and FFT-based spectral estimates are summarised. A brief guide to
      the implementation of FFT-based and AR spectral estimation techniques is given
      concentrating on data analysis packages that require little or no programming
      expertise. This review concludes that the AR modelling approach can produce
      tremor spectra that are superior to those from FFT-based methods for short data
      sequences. Although the spectral estimates are improved, the benefits of AR
      modelling for providing information about the physiological mechanisms of tremor
      generation are not yet clear.

PMID- 9765050
TI  - Nonlinear dynamic systems evaluation of rhythmic' eye movements (optokinetic
      nystagmus).
AB  - The last decade has seen a surge in the study of nonlinear dynamical behavior in
      physiologic systems. In this paper, some of the computational techniques most
      commonly used to investigate the nonlinear dynamics of these systems are
      described. Applications to eye movement analysis are included, including the
      validation of a mathematical model of optokinetic nystagmus (OKN) eye movements.
      OKN appears to have some nonlinear and deterministic component, along with
      significant randomness. Fast phase starting and ending points are somewhat
      predictable (deterministic), while so-called 'exceptional events' analysis shows
      that they also have a large random component. Surrogate data methods suggest that
      the population of slow and fast phases in OKN is more important than any specific
      relationship between adjacent slow and fast phases. Analysis of a statistical
      model for fast phase intervals indicates that the model data are slightly more
      random than the actual OKN.

PMID- 9765051
TI  - Identification of patterns of neuronal connectivity--partial spectra, partial
      coherence, and neuronal interactions.
AB  - The cross-correlation histogram has provided the primary tool for inferring the
      structure of common inputs to pairs of neurones. While this technique has
      produced useful results it not clear how it may be extended to complex networks.
      In this report we introduce a linear model for point process systems. The finite
      Fourier transform of this model leads to a regression type analysis of the
      relations between spike trains. An advantage of this approach is that the full
      range of techniques for multivariate regression analyses becomes available for
      spike train analysis. The two main parameters used for the identification of
      neural networks are the coherence and partial coherences. The coherence defines a
      bounded measure of association between two spike trains and plays the role of a
      squared correlation coefficient defined at each frequency lambda. The partial
      coherences, analogous to the partial correlations of multiple regression
      analysis, allow an assessment of how any number of putative input processes may
      influence the relation between any two output processes. In many cases analytic
      solutions may be found for coherences and partial coherences for simple neural
      networks, and in combination with simulations may be used to test hypotheses
      concerning proposed networks inferred from spike train analyses.

PMID- 9765052
TI  - On the optimal control of behaviour: a stochastic perspective.
AB  - Evolution is a closed stochastic optimisation process driven by the interaction
      between behaviour and environment towards local maxima in fitness. It is inferred
      that nervous systems are selected to provide optimal control of behaviour (the
      'assumption of optimality'), such that for some behaviours, the expectation of
      future hazards to survival are minimised. This is illustrated by goal-directed
      saccades in which minimising total flight-time of primary and secondary movements
      provides a better fit to observations than simply minimising the error of the
      primary movement. This optimisation is extended to intra-movement trajectories,
      where low-bandwidth (smooth) velocity profiles provide a more satisfactory
      description of observations than simple bang-bang control. Since minimum-time
      behaviours cannot be controlled by error feedback, it is concluded that the
      cerebellum must be executing a real-time unreferenced optimisation process. This
      requires explorative as well as exploitative behaviour. Stochastic gradient
      descent is discussed as a possible means by which the cerebellum may optimise
      behaviour.

PMID- 9765053
TI  - Restoration of PEX2 peroxisome assembly defects by overexpression of PMP70.
AB  - The mutant Chinese hamster ovary (CHO) cell line Z78/C has defective peroxisome
      assembly due to a missense mutation in PEX2, the gene which encodes the 35 kDa
      peroxisomal integral membrane protein. In humans, PEX2 mutations are responsible
      for complementation group 10 of the human peroxisome biogenesis disorders (PBD),
      a genetically heterogeneous group of lethal, autosomal recessive diseases
      including the Zellweger syndrome and related phenotypes. To develop additional
      cellular models for Zellweger syndrome, we produced a series of new mutant CHO
      cell clones in the same complementation group as Z78/C (Z2, Z7, Z22, and Z105).
      As expected, expression of human PEX2 restores peroxisomal biogenesis in all of
      these clones. Surprisingly, expression of the human 70 kDa peroxisomal membrane
      protein (PMP70) also restores peroxisome biogenesis in these same CHO cell
      clones. We confirmed this effect of PMP70 expression on peroxisome biogenesis by
      determining the subcellular latency of catalase, the immunohistochemical
      localization of catalase and the beta-oxidation of very long chain fatty acids
      (VLCFA). By contrast, expression of a mutant allele of PMP70 identified in a
      patient with Zellweger syndrome did not restore peroxisome biogenesis in the PEX2
      deficient CHO cell clones. Our results indicate that overexpression of PMP70
      suppresses the phenotype of PEX2 gene mutations. These observations suggest a
      functional interaction between PEX2 and PMP70 in the peroxisome membrane.

PMID- 9765054
TI  - Spatial differences in gap junction gating in the lens are a consequence of
      connexin cleavage.
AB  - Gap junctions in the vertebrate lens exhibit spatial differences in pH gating:
      those in the cortical fibre cells close upon tissue acidification while those in
      the core region do not. It has been speculated that this difference in channel
      gating is a consequence of the cleavage of the connexins (Cx) that form the gap
      junction channels. We report the construction of a truncation mutant of ovine
      Cx50 which mimicks the cleavage in the intact lens. The construct when expressed
      in Xenopus oocytes results in the formation of functional channels. Comparison
      with full-length Cx50 revealed a significant reduction in the pH-sensitivity of
      the truncated form. This is the first evidence linking the non-uniform gating of
      gap junction channels in the lens with connexin cleavage. It also reveals how
      fibre cells in the core region remain connected despite the acidic environment
      caused by elevated lactate levels.

PMID- 9765056
TI  - In situ detection of a fungal glycoprotein-elicitor in stem rust-infected
      susceptible and resistant wheat using immunogold electron microscopy.
AB  - Immunoelectron microscopy (IEM) was used to analyze the compatible and
      incompatible host-pathogen interaction between the obligate, biotroph stem rust
      (Puccinia graminis f.sp. tritici; Pgt) and primary leaves of wheat (Triticum
      aestivum L.). The investigation was focused on the subcellular localization of a
      fungal elicitor glycoprotein of stem rust (Pgt-elicitor). Uredospores as well as
      fungal infection structures of stem rust on wheat leaves were probed with a
      specific monoclonal antibody, in order to determine the in situ distribution
      pattern of the antigen. Binding to the anti-elicitor antibody was observed over
      the cell wall and the germ pore of germinating uredospores. Immunogold staining
      was found over the infection structures of stem rust within the wheat leaf tissue
      of both the compatible and incompatible plant-pathogen interaction. Distinct cell
      wall layers of the intercellular mycelium, of the haustorial mother cells, as
      well as of the haustoria were clearly labeled. Gold particles were also detected
      over the intercellular space and the extrahaustorial matrix in between the
      extrahaustorial membrane and the haustorial cell wall which indicated a release
      of elicitor molecules from the fungal cell wall. No labeling was observed over
      the host cell cytoplasm of the compatible and incompatible interaction,
      respectively. The immunocytochemical detection of elicitor epitopes over the
      hyphal cell walls of in vitro grown axenic cultures of P. graminis f.sp. tritici
      confirmed the occurrence of elicitor molecules in young hyphal material. Elicitor
      molecules were released by the hyphae of axenic cultures of stem rust in vitro.

PMID- 9765055
TI  - Phenotypical changes of a human pancreatic adenocarcinoma cell line after
      selection on laminin-1/nidogen (LM/Ng) substratum.
AB  - A cell line (PaTu 8902LM) exhibiting an altered phenotypic appearance was
      selected from a highly dedifferentiated established human pancreatic tumour cell
      line (PaTu 8902) by repetitive exposure to laminin-1/nidogen substratum and
      subsequent selection for adherent cells. Polymerase chain reaction analysis for
      repetitive DNA indicated that both cell lines are genetically very closely
      related. The original PaTu 8902 line consisted of flat cells growing in
      monolayers. In contrast, the obtained PaTu 8902LM cells exhibited a spherical
      morphology and tended to form clusters. Immunofluorescence analysis using
      antibodies against apical and basolateral marker enzymes indicated that the PaTu
      8902LM cells were polarized, arranging their apical surfaces around central
      lumenal structures when growing in clusters. In addition, the selected PaTu
      8902LM cell line exhibited altered levels of a number of differentiation marker
      enzymes like 5'-nucleotidase, transglutaminase and plasminogen activators. The
      different morphological characteristics of both cell lines were maintained even
      after injection into nude mice. In xenografts, PaTu 8902LM cells were grouped
      around lumenal, duct-like structures, whereas the original PaTu 8902 cell line
      formed solid tumours composed of undifferentiated cells. Evidence is presented
      that the PaTu 8902LM cells are not merely selected from preexisting cells, but
      that the exposure of PaTu 8902 cells to laminin-1/nidogen had induced a stable
      transdifferentiation towards the phenotype of the epithelial cells lining the
      pancreatic secretory ducts. Thus the PaTu 8902LM cells resemble more closely
      those cells from which tumours of the pancreas originate in vivo and therefore
      might be a useful cell system in future analyses of the biology of pancreatic
      tumours which are of increasing incidence and clinical importance.

PMID- 9765057
TI  - Preferential localization of exocytotic active zones in the terminals of neurite
      emitting chromaffin cells.
AB  - Amperometry using 2.5 microm radius carbon fiber electrodes was employed to study
      exocytotic catecholamine release from individual cultured bovine chromaffin
      cells. The secretory responses to either direct depolarization or nicotinic
      receptor stimulation were focal in nature in both round and neurite-emitting
      cells. In contrast to the random distribution of active sites found in round
      cells, bipolar and tripolar chromaffin cells had responsive zones preferentially
      located at neurite terminals as indicated by the lower probability of finding
      "silent" electrode positions and an increased nicotinic-receptor responsiveness
      when compared with the cell body. In agreement with these data we have observed a
      preferential deposition of dopamine-beta-hydroxylase into the neurite terminal
      plasmalemma after stimulation of intact cells. These observations might be of
      interest since the differences in the distribution of secretory "spots" between
      round and neurite-emitting chromaffin cells could be used to study the molecular
      factors determining active site localization.

PMID- 9765058
TI  - Characterization of glial filament-cytoskeletal interactions in human
      astrocytomas: an immuno-ultrastructural analysis.
AB  - The role that glial filaments play in cells and tumors of glial origin is not
      well understood. We therefore undertook the present study to determine the
      relationships between glial and vimentin intermediate filaments (IFs), actin
      microfilaments, and CD44, a cell surface glycoprotein important in cell migration
      and invasion, in human astrocytoma cells. Three astrocytoma cell lines, U343 MG-A
      (U343), U251 MG (U251), and antisense GFAP-transfected U251 (asU251) were studied
      using immunofluorescence confocal and immunoelectron microscopy. Furthermore, we
      studied the phenotypic behaviour of these astrocytoma cell lines by analyzing
      their migration through Matrigel in vitro. U343 astrocytoma cells had the highest
      expression levels of glial fibrillary acidic protein (GFAP), whereas asU251 had
      virtually no expression of GFAP. Parental U251 cells had intermediate expression
      levels of GFAP. The elimination of GFAP expression in as U251 cells was
      accompanied by a marked increase in vimentin, actin microfilaments and CD44
      levels. Gold labeling density counts of cytoskeletal and cell surface elements
      demonstrated that the differences between GFAP, actin, CD44 and vimentin levels
      in the different astrocytoma cell lines were statistically significant (p <
      0.05). Results from the in vitro invasion assay revealed that U343 cells
      demonstrated the least invasive potential, whereas asU251 astrocytoma cells
      demonstrated the most. Our results show that elimination of GFAP expression by
      antisense leads to marked alterations in cell morphology and phenotypic
      behaviour. These data imply that GFAP may be linked spatially and functionally to
      cytoskeletal elements which may be altered when this IF is deleted in
      astrocytomas.

PMID- 9765059
TI  - Subcellular localization and possible function of actin, tropomyosin and actin
      related protein 3 (Arp3) in the fission yeast Schizosaccharomyces pombe.
AB  - We investigated subcellular localizations and interactions of actin and two actin
      cytoskeleton-related proteins, Cdc8 tropomyosin and actin-related protein 3,
      Arp3, in the fission yeast Schizosaccharomyces pombe, using specific antibodies
      and by gene disruption. Actin was localized to the medial microfilamentous ring
      in the region of the septum during cytokinesis and to cortical patches by
      immunoelectron microscopy. F-actin cables were detected throughout the cell cycle
      by fluorescent staining with Bodipy-phallacidin. Cables were often linked to the
      patches and to the medial ring during its formation. Tropomyosin was localized to
      the medial ring and the cables. It was also distributed in the cell as patches,
      although co-localization with F-actin was not frequent. In cdc8ts mutant cells, F
      actin cables were not observed although the F-actin patches were detected and
      cell polarity was maintained. These observations suggest that the F-actin cables
      may be involved in the formation of the medial ring, and that tropomyosin plays
      an important role in organizing both the ring and the cable, but is not involved
      in the F-actin patch formation or maintenance of cell polarity. Binding of Arp3
      to actin was revealed by immunoprecipitation as well as by DNase I column
      chromatography. Arp3 seemed to form a complex with several proteins in the cell
      extracts, as previously reported for other organisms. Contrary to a previous
      report (McCollum et al., EMBO J. 15, 6438-6446, 1996), Arp3 was found to be
      concentrated in the medial region from early anaphase to late cytokinesis.
      Following arp3 gene disruption, F-actin patches were delocalized throughout the
      cell and cells did not undergo polarized growth, suggesting that Arp3 influences
      the proper localization of the actin patches in the cell and thereby controls the
      polarized growth of the cell.

PMID- 9765060
TI  - Toxicokinetics of soman in cerebrospinal fluid and blood of anaesthetized pigs.
AB  - The toxicokinetics of the four stereoisomers of the nerve agent C(+/-)P(+/-)
      soman was analysed in cerebrospinal fluid (CSF) and blood in anaesthetized,
      spontaneously breathing pigs during a 90-min period after injection of soman. The
      pigs were challenged with different intravenous (i.v.) doses of C(+/-)P(+/-)
      soman corresponding to 0.75-3.0 LD50 (4.5, 9.0 and 18 microg/kg in a bolus
      injection and 0.45 microg/kg per min as a slow infusion). Artificial ventilatory
      assistance was given if, after soman intoxication, the respiratory rate decreased
      below 19 breaths/min. Blood samples were taken from a femoral artery and CSF
      samples from an intrathecal catheter. The concentrations of the soman isomers
      were determined by gas chromatography coupled with high resolution mass
      spectrometry. All four isomers of soman were detected in both blood and CSF
      samples. The relatively non-toxic C(+/-)P(+) isomers disappeared from the blood
      stream and CSF within the first minute, whereas the levels of the highly toxic
      C(+/-)P(-) isomers could be followed for longer, depending on the dose.
      Concurrently with the soman analyses in blood and CSF, cholinesterase (ChE)
      activity and cardiopulmonary parameters were measured. C(+/-)P(-) isomers showed
      approx. 100% bioavailability in CSF when C(+/-)P(+/-)-soman was given i.v. as a
      bolus injection. In contrast, C(+/-)P(-) isomers displayed only 30%
      bioavailability in CSF after slow i.v. infusion of soman. The ChE activity in
      blood decreased below 20% of baseline in all groups of pigs irrespective of the
      soman dose. The effect of soman intoxication on the respiratory rate, however,
      seems to be dose-dependent and the reason for ventilatory failure and death.
      Artificial ventilation resulted in survival of the pigs for the time-period
      studied.

PMID- 9765061
TI  - Serum and urinary boron levels in rats after single administration of sodium
      tetraborate.
AB  - The pharmacokinetics of boron was studied in rats by administering a 1 ml oral
      dose of sodium tetraborate solution to several groups of rats (n=20) at eleven
      different dose levels ranging from 0 to 0.4 mg/100 g body weight as boron. Twenty
      four-hour urine samples were collected after boron administration. After 24 h the
      average urinary recovery rate for this element was 99.6+/-7.9. The relationship
      between boron dose and excretion was linear (r=0.999) with a regression
      coefficient of 0.954. This result suggests that the oral bioavailability (F) of
      boron was complete. Another group of rats (n=10) was given a single oral
      injection of 2 ml of sodium tetraborate solution containing 0.4 mg of boron/100 g
      body wt. The serum decay of boron was followed and found to be monophasic. The
      data were interpreted according to a one-compartment open model. The appropriate
      pharmacokinetic parameters were estimated as follows: absorption half-life,
      t1/2a=0.608+/-0.432 h; elimination half-life, t1/2=4.64+/-1.19 h; volume of
      distribution, Vd = 142.0+/-30.2 ml/100 g body wt.; total clearance, Ctot=0.359+/
      0.0285 ml/min per 100 g body wt. The maximum boron concentration in serum after
      administration (Cmax) was 2.13+/-0.270 mg/l, and the time needed to reach this
      maximum concentration (Tmax) was 1.76+/-0.887 h. Our results suggest that orally
      administered boric acid is rapidly and completely absorbed from the
      gastrointestinal tract into the blood stream. Boric acid in the intravascular
      space does not have a strong affinity to serum proteins, and rapidly diffuses to
      the extravascular space in proportion to blood flow without massive accumulation
      or binding in tissues. The main route of boron excretion from the body is via
      glomerular filtration. It may be inferred that there is partial tubular
      resorption at low plasma levels. The animal model is proposed as a useful tool to
      approach the problem of environmental or industrial exposure to boron or in cases
      of accidental acute boron intoxication.

PMID- 9765062
TI  - Urinary excretion kinetics of 1-hydroxypyrene following intravenous
      administration of binary and ternary mixtures of polycyclic aromatic hydrocarbons
      in rat.
AB  - The effect of exposure to binary and ternary mixtures of polycyclic aromatic
      hydrocarbons (PAHs) on the urinary excretion kinetics of 1-hydroxypyrene (1-OHP)
      has been examined. Male Sprague-Dawley rats were administered intravenously 5
      micromol/kg of pyrene alone or in combination with 0.5, 5 and 25 micromol/kg of
      either naphthalene, benzo(a)pyrene (BaP), or both. Urine samples were collected
      at frequent intervals over 48 h. The kinetics of 1-OHP in urine was not altered
      by the presence of either naphthalene or BaP in the mixtures, at least from 4 h
      post-dosing. Hence, none of the injected mixtures significantly modified the
      first-order apparent elimination half-life of 1-OHP in urine obtained for the 12
      to 42 h period post injection where mean values ranged between 6.2 and 9.6 h.
      However, while the presence of naphthalene or the low BaP dose of 0.5 micromol/kg
      in the mixtures did not have a significant effect on the total excretion of 1
      OHP, BaP doses of 5 and 25 micromol/kg in the mixtures significantly increased
      the amount of 1-OHP excreted in urine. Mean percentages of the pyrene dose
      excreted as 1-OHP after injection of pyrene in combination with 0.5, 5 and 25
      micromol/kg BaP were respectively increased 1.3, 2.2 and 2.6 times compared to
      the value obtained after administration of pyrene alone. The percentages
      determined after concomitant administration of pyrene and 0.5, 5 and 25
      micromol/kg of BaP plus naphthalene were 1.4, 1.8 and 2.4 times, respectively,
      the value obtained after administration of pyrene singly. The observed effect of
      BaP (5 or 25 micromol/kg) on 1-OHP total excretion appears to result from BaP
      induction of pyrene metabolism. Lack of effect of naphthalene appears to be due
      to its weak P450 1A1 enzyme induction capacity. Absence of significant effect of
      the low BaP dose in the mixtures (0.5 micromol/kg) suggests that 1-OHP in urine
      is useful as a bioindicator of occupational and environmental exposures to PAH
      mixtures.

PMID- 9765063
TI  - Toxicokinetics of 1,2,4-trimethylbenzene in humans exposed to vapours of white
      spirit: comparison with exposure to 1,2,4-trimethylbenzene alone.
AB  - This study compares the toxicokinetics of inhaled 1,2,4-trimethylbenzene (124TMB)
      in men exposed to white spirit with that previously observed in the same
      individuals exposed to 124TMB alone. The appropriateness of using
      dimethylhippuric acid (DMHA) metabolites of 124-, 123- and 135TMB in urine as
      biomarkers of exposure is also addressed and the kinetics of n-decane, n-undecane
      and 123TMB is investigated. The toxicokinetics of 124TMB was studied in nine
      male, healthy volunteers exposed to solvent vapours in an exposure chamber for 2
      h during a work load of 50 W. The subjects were exposed to 2 ppm (11 mg/m3) of
      124TM B during exposure to 300 mg/m3 of white spirit. The 124TMB isomer was
      analysed in blood, urine and exhaled air by gas chromatography. The DMHA
      metabolites of all three TMB isomers were analysed in urine by high-performance
      liquid chromatography. The results were compared with previously published
      exposures to 2 and 25 ppm (120 mg/m3) of 124TMB vapour alone. In addition, the
      occurrence of acute effects was studied by means of a questionnaire. Irritation
      and central nervous system (CNS) symptoms were recorded by ratings on a 100 mm
      visual analogue scale. Blood levels of 124TMB and excretion rates of 3,4-DMHA in
      urine were markedly elevated both during and after exposure to white spirit
      compared to the same exposure level of 124TMB alone. No irritation or CNS effects
      were reported in the questionnaire at any exposure condition. It appears that
      components in white spirit interfere with the metabolic elimination of 124TMB.
      This should be considered in biological exposure monitoring as well as in risk
      assessment.

PMID- 9765064
TI  - Differential alterations in levels of hepatic microsomal cytochrome P450 isozymes
      following intracerebroventricular injection of bacterial lipopolysaccharide in
      rats.
AB  - To investigate the effect of central inflammation due to bacterial infection,
      such as meningitis, on the activities of hepatic cytochromes P450 (CYPs), rats
      were injected intracerebroventricularly (i.c.v.) with 0.1 microg of bacterial
      lipopolysaccharide (LPS). The LPS i.c.v. injection significantly decreased the
      total P450 contents (by 30% of the levels of control rats treated with saline
      i.c.v.), the contents of CYP1A (48%), 2B (54%), 2C11 (37%) and 3A (40%) and
      related drug metabolizing activities, 7-ethoxycoumarin O-deethylation (36%),
      imipramine N-demethylation (41%) and erythromycin N-demethylation (33%) in liver
      microsomes 24 h after the treatment. In contrast, intraperitoneal (i.p.)
      injection of LPS at the same dose as i.c.v. (0.1 microg) did not significantly
      affect the hepatic microsomal contents of total P450 or the content of each
      individual CYP isozyme and its activity. CYP2D1 protein and the activity of
      imipramine 2-hydroxylase were not significantly decreased by LPS injection
      regardless of the route of administration. The inhibitory effects of 0.1 microg
      i.c.v. LPS on the activities of these CYPs were almost equal to those of 10
      microg i.p. LPS, and 0.01 microg of i.c.v. LPS significantly decreased the
      activity of imipramine N-demethylase only. Therefore, the LPS i.c.v. injection
      resulted in CYP isozyme-selective inhibition at an ineffective dose when injected
      i.p.. It is suggested that a central inflammation, such as meningitis,
      differentially decreases the levels of hepatic CYP isozymes. A possible
      involvement is discussed of the central nervous system in this down-regulation.

PMID- 9765065
TI  - Biomonitoring of aromatic amines V: acetylation and deacetylation in the
      metabolic activation of aromatic amines as determined by haemoglobin binding.
AB  - Aromatic amines are metabolically activated by N-oxidation of either the amine or
      the acetamide as a first step and esterification of the resulting N-hydroxyl
      derivatives as a second step. Both pathways may lead to DNA-adducts and
      subsequently to DNA lesions and mutations. Since the accumulation of non
      acetylated adducts has been associated with tumour initiating properties, the
      balance between acetylation and deacetylation may greatly influence the
      biological effect. Hydrolysable haemoglobin adducts representing the
      bioavailability of N-hydroxylamines and the corresponding nitroso-derivatives
      were analysed following oral administration to female Wistar rats of two
      arylamine-acetamide couples: 4-aminobiphenyl and 2-aminofluorene, and two
      arylamine-acetamide-diacetamide triples: benzidine and 3,3'-dichlorobenzidine.
      The results show that the monoacetamides are readily deacetylated in vivo whereas
      the diacetamides are not. A dynamic equilibrium is indicated to exist between
      acetylation and deacetylation, which depends on substrate specificity, and the
      role of deacetylation is emphasised. In addition, acetylation polymorphism was
      studied with 4-chloroaniline and 3,3'-dichlorobenzidine in slow acetylating A/J
      and rapid acetylating C57BL/6J mice. The slow acetylator genotype was associated
      with significantly higher haemoglobin-adduct levels for both arylamines. The
      results provide additional support for the use of haemoglobin adducts in
      biomonitoring as a dosimeter for the biologically active dose of
      arylamines/arylacetamides. Moreover, biomonitoring of haemoglobin adducts may
      provide information about an individual's susceptibility to the toxic and
      carcinogenic effects of these chemicals.

PMID- 9765066
TI  - Correlation of 32P-postlabelling-detection of DNA adducts in mouse skin in vivo
      with the polycyclic aromatic compound content and mutagenicity in Salmonella
      typhimurium of a range of oil products.
AB  - The in vivo genotoxic activities in mouse skin of the dimethyl sulphoxide (DMSO)
      extracts of a range of oil products [residual aromatic extract; untreated heavy
      paraffinic distillate aromatic extract; mildly refined light naphthenic base oil;
      bitumen (vacuum residue); high viscosity index base oil obtained by catalytic
      hydrogenation] were evaluated by 32P-postlabelling DNA analysis. The results of
      quantitative 32P-postlabelling analyses of epidermal DNA from mice treated with
      the DMSO extracts showed linear relationships with the total polycyclic aromatic
      compound (PAC) contents, determined by the Institute of Petroleum method IP 346
      and also the 3-6 ring PAC contents, measured by on-line liquid-liquid extraction
      using flow injection analysis. The 32P-postlabelling data also showed a linear
      relationship with the mutagenicity indices of these oil products determined in S.
      typhimurium TA98 using the modified Ames Salmonella microsome test. The in vivo
      genotoxicity of the DMSO extracts from the oil products was low, judged by 32P
      postlabelling analysis of DNA adducts measured in epidermal DNA of treated mouse
      skin, and ranging from 2 to 723 attomole/microg DNA per mg oil product. The in
      vivo 32P-postlabelling data from this study are consistent with these materials
      expressing low genotoxicity in mouse skin in vivo. The DMSO extraction procedure
      coupled with 32P-postlabelling DNA analysis is useful for ranking the relative
      genotoxic potency in vivo of a wide range of oil products. In general the trend
      observed is similar to rankings based on physicochemical measurements of total
      PAC contents or 3 6 ring PAC contents of the oil products.

PMID- 9765067
TI  - Stereospecificity of the sensory irritation receptor for nonreactive chemicals
      illustrated by pinene enantiomers.
AB  - To clarify the existence of a receptor protein for sensory irritants in
      trigeminal nerve endings, D- [i.e. (+)] and L- [i.e. (-)] enantiomers of alpha-
      and beta-pinene as models of nonreactive chemicals were evaluated for their
      potency in outbred OF1 and NIH/S mice using ASTM E981-84 bioassay. All pinenes
      possess sensory irritation properties and also induced sedation and signs of
      anaesthesia but had no pulmonary irritation effects. According to the ratio of
      RD50 (i.e. concentration which causes a 50% decrease in respiratory rate,f) and
      vapour pressure (Po), all pinenes are nonreactive chemicals. For nonreactive
      chemicals, Po and olive oil-gas partition (Loil) can be used to estimate their
      potency as sensory irritant. Thus, for enantiomers with identical physicochemical
      properties, the estimated RD50 values are the same. In addition, although alpha-
      and beta-pinene do not have identical Po and Loil values, their estimated
      potencies are quite close. However, the experimental results showed that D
      enantiomers of pinenes were the most potent as sensory irritants and a difference
      in potency also exists between alpha- and beta-pinene. RD50 for D-enantiomers of
      alpha- and beta-pinene were almost equal, 1053 ppm and 1279 ppm in OF1 strain and
      1107 ppm and 1419 ppm in NIH/S strain, respectively. Values differed by a factor
      of approximately 4 to 5 from L-beta-pinene for which the RD50 was 4663 ppm in OF1
      and 5811 ppm in NIH/S mice. RD50 could not be determined for L-alpha-pinene; this
      pinene was almost inactive. D-alpha-pinene seems to best fit the receptor because
      its experimental RD50 was one-half of the estimated value while for D-beta-pinene
      those values were equal. On the contrary, L-beta-pinene was about 3 to 4 times
      less potent than estimated. L-alpha-pinene was only slightly active although it
      was estimated to be as potent as D-alpha-pinene. The remarkable difference in
      potency between L-enantiometers is most likely due to a structural difference
      between alpha- and beta-pinene: the more flexible beta-pinene can bend to fit
      into the receptor better than the rigid alpha-pinene. The results showed that the
      commonly used physicochemical descriptors cannot fully explain the potency of
      these chemicals; their three-dimensional structure should also be considered.
      Because of the stereospecificity of pinenes, a target site for nonreactive
      sensory irritants is most likely a receptor protein containing a chiral
      lipophilic pocket.

PMID- 9765068
TI  - The toxic mechanism and metabolic effects of atractyloside in precision-cut pig
      kidney and liver slices.
AB  - The toxic and cellular metabolic effects of atractyloside, a diterpenoid
      glycoside, which causes fatal renal and hepatic necrosis in vivo in animals and
      humans, have been investigated in tissue slices prepared from male domestic pig
      kidney and liver. Precision-cut slices (200 microm thick) were incubated with
      atractyloside at concentrations of 200 microM, 500 microM, 1.0 mM and 2.0 mM for
      3 h at 37 degrees C and changes in lipid profile and pyruvate-stimulated
      gluconeogenesis investigated. Lipid peroxidative changes, reduced glutathione
      (GSH) and ATP content, the release of lactate dehydrogenase (LDH), alkaline
      phosphatase (ALP), alanine and aspartate aminotransferase (ALT/AST) were also
      assessed. After 3 h of incubation, atractyloside caused a significant (P < 0.01)
      and concentration-dependent leakage of LDH and ALP from kidney slices. Only LDH
      leakage was significantly elevated in liver slices while ALT and AST leakage
      showed marginal increase. Atractyloside at concentrations of > or =200 microM
      caused a significant increase in lipid peroxidation, but only in liver slices.
      However, atractyloside at concentrations of > or =200 microM caused a marked
      depletion of GSH and ATP content in both kidney and liver slices. There was a
      marked decrease in total and individual phospholipid in kidney but not in liver
      slices. However, cholesterol and triacylglycerol levels were not affected by
      atractyloside in both kidney and liver slices. Renal and hepatic pyruvate
      stimulated gluconeogenesis were significantly (P < 0.05) inhibited at
      atractyloside concentrations of > or =500 microM. Accumulation of organic anion p
      amino-hippuric acid (PAH) was also inhibited in renal cortical slices at
      atractyloside concentrations of > or =500 microM. These results suggest that the
      observable in vivo effect of atractyloside can be reproduced in slices and that
      basic mechanistic differences exist in the mode of toxicity in liver and kidney
      tissues. The data also raise the possibility that the mechanistic basis of
      metabolic alterations in these tissues following treatment with atractyloside may
      be relevant to target selective toxicity.

PMID- 9765069
TI  - Glutamine transaminase K intranephron localization in rats determined by urinary
      excretion after treatment with segment-specific nephrotoxicants.
AB  - Glutamine transaminase K(GTK) excretion assessed in urine and by kidney histology
      was evaluated in rats after single treatment with 1.0 mg/kg i.p. of mercuric
      chloride, 100 mg/kg i.p. of hexachloro-1:3-butadiene (both S3, pars recta,
      segment-specific nephrotoxicants) and 25 mg/kg s.c. of potassium dichromate (S1
      S2, pars convoluta, segment-specific nephrotoxicant). The aim was to correlate
      segment-specific injury and enzyme excretion in order to assess, using non-vasive
      methods, localization of GTK along the proximal tubule. Mercuric chloride and
      hexachloro-1:3-butadiene produced early focal damage in the pars recta (focal
      necrosis was shown 10 h after treatment, and diffuse necrosis appeared later at
      34 and 24 h after treatment). Changes of the pars convoluta were occasional and
      delayed (72 h after treatment for both substances). On the contrary, potassium
      dichromate induced damage of the pars convoluta (vacuolar degeneration and focal
      necrosis were evident 24 h and 48 h after treatment, respectively), whereas the
      pars recta was affected later (focal vacuolar degeneration was observed 72 h
      after treatment). Increase urinary GTK excretion was early after treatment with
      mercuric chloride and hexachloro-1:3-butadiene (significant increase was observed
      within 10 h), with a peak for both substances 24 h after treatment, in agreement
      with the necrosis of the pars recta. Potassium dichromate induced a significant
      increase of enzyme excretion in urine also 24 h after injection, according to
      histological features showing vacuolar degeneration of the pars convoluta; the
      peak of excretion was reached 48 h after treatment (delay was due, probably, to
      s.c. administration). The results show that GTK increased in urine after
      treatment with S3 and S1-S2 specific nephrotoxicants; the combination of
      histological examination and urinary enzyme supports the evidence that the enzyme
      is distributed along the whole of the proximal tubule.

PMID- 9765070
TI  - Reduction of cisplatin toxicity in cultured renal tubular cells by the
      bioflavonoid quercetin.
AB  - Quercetin (QC), a polyphenolic compound widely distributed in fruits and
      vegetables has recently gained interest due to its cisplatin (CP) sensitizing
      properties in cancer cells. It is currently unknown, whether quercetin also
      increases the susceptibility of the kidneys to cisplatin toxicity. We studied the
      effects of various bioflavonoids on CP toxicity in an in vitro model of cultured
      tubular epithelial cells (LLC-PK1). Viability of LLC-PK1 cells, as assessed by
      lactate dehydrogenase (LDH) release and MTT-test, was affected by CP (100-400
      microM) in a time and dose dependent fashion. Pretreatment of cells with QC for 3
      h significantly reduced the extent of cell damage. The protective activity of QC
      was concentration dependent, starting at 10-25 microM and reaching a plateau
      between 50 and 100 microM. Other bioflavonoids (catechin, silibinin, rutin) did
      not diminish cellular injury, even at higher concentrations (100-500 microM).
      Quercetin itself showed some intrinsic cytotoxicity at concentrations exceeding
      75 microM. Our data indicate that quercetin reduces cisplatin toxicity in
      cultured tubular epithelial cells. The exact mechanism of protection is unclear,
      though scavenging of free oxygen radicals may play an important role.

PMID- 9765071
TI  - Reduction of thyroid hormone levels by methylsulfonyl metabolites of
      polychlorinated biphenyl congeners in rats.
AB  - Male Sprague-Dawley rats received four consecutive intraperitoneal doses of four
      kinds of methylsulfonyl (MeSO2) metabolites of polychlorinated biphenyl (PCB)
      congeners: 3-MeSO2-2,2',3',4',5,6-hexachlorobiphenyl (3-MeSO2-CB132); 3-MeSO2
      2,2',3',4', 5,5'-hexachlorobiphenyl (3-MeSO2-CB141); 3-MeSO2-2,2',4',5,5',6
      hexachlorobiphenyl (3-MeSO2-CB149) and 4-MeSO2-2,2',4',5,5',6-hexachlorobiphenyl
      (4-MeSO2-CB149). The congeners were major MeSO2-PCBs determined in human milk,
      liver and adipose tissue, and the aim was to determine their effect on thyroid
      hormone levels. All four tested MeSO2 metabolites (20 micromol/kg once daily for
      4 days) reduced serum total thyroxine levels by 22-44% at a much lower dose than
      phenobarbital (PB; 431 micromol/kg once daily for 4 days) on days 2, 3, 4 and 7
      after the final doses. Total triiodothyronine levels were reduced 37% by
      treatment with 4-MeSO2-CB149 at day 7. A 30% increase in thyroid weight was
      produced by 3-MeSO2-CB141 treatment. Total cytochrome P450 content was increased
      by 3-MeSO2-CB132, 3-MeSO2-CB141 and 3-MeSO2-CB149, but not by 4-MeSO2-CB149.
      Thus, it is likely that the 3-MeSO2-hexachlorobiphenyls and 4-MeSO2-CB149 could
      influence the thyroid hormone metabolism by different mechanism(s). The results
      show that tested 3- and 4-MeSO2 metabolites of PCB congeners reduce thyroid
      hormone levels much more than PB in rats. Our finding suggests that the
      metabolites may act as endocrine-disrupters.

PMID- 9765072
TI  - History and future of endoscopic ultrasonography.

PMID- 9765073
TI  - Technical advances and future developments in endoscopic ultrasonography.

PMID- 9765074
TI  - Clinical applications of endobronchial ultrasonography in lung diseases.

PMID- 9765075
TI  - Intraluminal ultrasonography in urology.

PMID- 9765077
TI  - EUS training in the USA.

PMID- 9765076
TI  - EUS training in Europe.

PMID- 9765078
TI  - Education and training in endoscopic ultrasound in Japan.

PMID- 9765079
TI  - EUS instruments for esophageal lesions.

PMID- 9765080
TI  - The diagnostic value of transendoscopic miniature ultrasonic probe for esophageal
      diseases.
AB  - BACKGROUND AND STUDY AIMS: To investigate the value of a transendoscopic
      miniature ultrasonic probe (USP) in the diagnosis of esophageal diseases.
      PATIENTS AND METHODS: Endoscopic ultrasonography was performed by means of USP in
      53 patients with esophageal diseases, including 16 with esophageal leiomyoma, 14
      with esophageal carcinoma, seven with achalasia, seven with reflux esophagitis,
      six with esophageal polyps and three with esophageal varices. RESULTS: USP
      clearly showed all 16 esophageal leiomyomas, whereas, conventional EUS could not
      show five small leiomyomas less than 1.0 x 1.0 cm in size. The appearance of
      esophageal leiomyoma was that of a hypoechoic mass with a homogeneous inner
      echogram arising from the fourth hypoechoic layer. All 14 patients with
      esophageal carcinoma underwent full endosonographic T and N staging with USP. In
      two cases passage of the malignant stenosis proved to be impossible using
      conventional EUS. The accuracy of USP on T staging and N staging was 80% and 30%,
      respectively. In the seven achalasia patients USP demonstrated a seven-layer
      structure of the esophageal wall, with thickening of the third and fifth layers.
      In the seven patients with reflux esophagitis no difference was found for the
      ultrasonic image between that with and that without Barrett's epithelium. All of
      the esophageal polyps were showed by USP as hypoechoic homogeneous lesion with
      indistinct margins. After endoscopic sclerotherapy the ultrasonographic feature
      of esophageal varices changed from submucosal multiple anechoic areas to high
      echoic areas. CONCLUSION: With refinement, the transendoscopic miniature
      ultrasonic probe will play an increasing role in the diagnosis of esophageal
      disease.

PMID- 9765081
TI  - Diagnosis and staging of esophageal carcinoma by endoscopic ultrasonography.

PMID- 9765082
TI  - Modified soft-balloon methods during ultrasonic probe examination for superficial
      esophageal cancer.
AB  - BACKGROUND AND STUDY AIMS: In ultrasonic probe studies for early-stage esophageal
      cancer the original soft-balloon method utilizing a condom had succeeded in
      obtaining a clear and reproducible picture by keeping deaerated water in a
      condom; however, the condom, which covered the endoscope lens, eliminated the
      usual endoscopic sight. Therefore, the authors endeavored to develop a modified
      method which enables both normal endoscopic observation and ultrasonic probe
      study with only a single insertion of the endoscope. PATIENTS AND METHODS: Thirty
      one patients with superficial esophageal cancer were included in this pilot
      study. As modifications of the soft-balloon technique, two novel methods of
      'wrapping' and 'invagination' were developed. RESULTS: These modifications are
      considered to have solved the above-mentioned problem and enable one to acquire
      both normal endoscopic photos and ultrasonic probe images during the same
      insertion of the endoscope. CONCLUSION: In a pilot study novel modifications
      improved the method of ultrasonic probe study for superficial esophageal cancer.

PMID- 9765083
TI  - Endoscopic ultrasonography in diagnosis and mucosal resection for early
      esophageal cancer.

PMID- 9765084
TI  - Endosonographic evaluation of the patient with achalasia.
AB  - Using endosonography, esophageal wall thickening is commonly observed in patients
      with achalasia. Imaging artifacts with the endosonographic appearance of an
      esophageal tumor in some patients with achalasia suggest that endosonographic
      images must be interpreted with caution. The endosonographer must be aware of
      anatomical peculiarities (dilated, tortuous, or "sigmoid" esophagus) and imaging
      techniques (tangential imaging) that may lead to artifactual imaging, and thereby
      avoid misinterpretation of results. Failure to recognize such imaging artifacts
      may lead to an erroneous diagnosis of pseudoachalasia, thereby subjecting
      patients to unnecessary surgery. Future applications of endoscopic
      ultrasonography for patients with achalasia may include endosonographically
      guided therapy. Prospective analyses of EUS-guided therapy are anticipated.

PMID- 9765085
TI  - Indications of endoscopic ultrasound in gastric lesions.

PMID- 9765086
TI  - Role of endoscopic ultrasonography for gastric lesions.

PMID- 9765087
TI  - Miniprobe or ultrasound endoscope for gastric lesions?

PMID- 9765088
TI  - Staging of gastric cancer with endoscopic ultrasonography and endoscopic mucosal
      resection.
AB  - Since it was found that the gastrointestinal wall is visualized as a five-layered
      structure corresponding to the histological layers of the wall, endoscopic
      ultrasonography (EUS) has become recognized clinically as the most accurate
      method for diagnosing and assessing the local staging of gastric cancer. However,
      some problems have remained, including how to differentiate between cancer
      invasion and ulcer fibrosis, how to detect microinvasion, and how to recognize
      malignant lymph nodes. Using the pattern analysis for depressed-type gastric
      cancer, it is usually possible to distinguish between cancer invasion and ulcer
      fibrosis, except in cases of microinvasion into ulcer fibrosis or inadequate
      scanning. However, the sensitivity of EUS for evaluating metastatic lymph nodes
      is still problematic. Endoscopic mucosal resection (EMR) for early gastric cancer
      has been widely accepted as a standard treatment in Japan due to its minimal
      invasiveness. According to our data, the overall rate of radical resection was
      68.3% (168 of 246), and 31.7% of the remaining patients additionally received
      laser treatment, surgery, or heater-probe treatment. There were no deaths owing
      to gastric cancer. Some lesions in which there was microinvasion of the submucosa
      were incorrectly diagnosed by EUS. It may be possible to solve this problem using
      three-dimensional EUS (3D-EUS) in the near future.

PMID- 9765089
TI  - Endoscopic ultrasonography diagnosis in submucosal tumor of stomach.

PMID- 9765091
TI  - Endoscopic ultrasonography for the diagnosis of gastric malignant lymphoma.

PMID- 9765090
TI  - Endoscopic ultrasonography in large gastric folds.
AB  - Large gastric folds are seen in a great number of benign and malignant
      conditions. Diagnosis is a clinical challenge because the etiology may be
      extremely varied and standard biopsies are often inconclusive. The gastric wall
      is considered thickened at endosonography when it is more than 3.6 mm in width.
      Different diseases show different levels of infiltration of the gastric wall.
      When abnormalities involve the second layer only, benign conditions can be
      considered and standard endoscopic biopsies are often diagnostic. When
      abnormalities involve layers two and three, different diseases can be suspected,
      including Helicobacter pylori infection and lymphoma; in this case large-particle
      biopsy should be considered. When abnormalities involve layer four, malignancy
      should be strongly suspected even if standard or large-particle biopsies are
      negative. Endosonography, always in combination with fine-needle or guillotine
      needle biopsy, should be able to rule out malignancies and to select the most
      appropriate treatment for each patient.

PMID- 9765092
TI  - Indications for endoscopic ultrasonography in colorectal lesions.

PMID- 9765093
TI  - Endoscopic ultrasonography versus probe for diagnosis of depth of infiltration of
      colorectal cancer.

PMID- 9765094
TI  - Endosonographic diagnosis of colorectal cancer.

PMID- 9765095
TI  - Endoscopic ultrasonography staging of superficial-type colorectal neoplasms for
      mucosectomy.

PMID- 9765096
TI  - Endoscopic ultrasonography in the evaluation of inflammatory bowel disease.

PMID- 9765097
TI  - Differential diagnosis of mucin-producing tumors of the pancreas by intraductal
      ultrasonography and peroral pancreatoscopy.
AB  - BACKGROUND AND STUDY AIMS: Although mucin producing tumors of the pancreas have
      been recently recognized as premalignant or malignant neoplasms, their diagnosis
      and management have been undetermined as yet. The aim of this study was to
      evaluate the capability of intraductal ultrasonography (IDUS) and peroral
      pancreatoscopy (PPS) in the differential diagnosis of mucin-producing tumors
      compared to that of other diagnostic tools. PATIENTS AND METHODS: From 1986 to
      1997, 31 patients with mucin-producing tumors of the pancreas underwent surgery.
      RESULTS: Histologically, in patients with adenocarcinoma, papillary tumorous
      lesions within the pancreatic ducts were 3 mm or more in maximum height. The
      detection rates for such lesions were 29% with US, 21% with CT, 86% with EUS,
      100% with IDUS and 83% with PPS. In patients with adenocarcinoma, PPS revealed
      taller papillary lesions with redness and/or capillary vessels. Biopsy and
      cytology during ERCP and under PPS direct vision had a sensitivity of about 60 %
      in the differential diagnosis between malignancy and benign diseases.
      CONCLUSIONS: Mucin-producing tumors of the pancreas with papillary tumorous
      lesions of 3 mm or more in maximum height should be considered as
      adenocarcinomas. The combined use of IDUS and PPS with biopsy and cytology is now
      considered the best for the differential diagnosis of mucin-producing tumors of
      the pancreas.

PMID- 9765098
TI  - Staging of pancreatic carcinoma by endoscopic ultrasonography.

PMID- 9765099
TI  - Endoscopic ultrasonography diagnosis of pancreatic cystic disease.

PMID- 9765101
TI  - Role of endoscopic ultrasound in the diagnosis of cholestasis.

PMID- 9765100
TI  - Diagnosis of chronic pancreatitis by endoscopic ultrasonography.

PMID- 9765102
TI  - Ultrasound probes for biliary lesions.

PMID- 9765103
TI  - Endoscopic ultrasonography diagnosis of gallbladder lesions.

PMID- 9765104
TI  - Staging of ampullary carcinoma by endoscopic ultrasonography.

PMID- 9765105
TI  - Staging of bile duct carcinoma by EUS and IDUS.

PMID- 9765107
TI  - A means of increasing the use of endoscopic ultrasonography: a newly developed
      thin video echoendoscope.

PMID- 9765106
TI  - Video echoendoscopy in the United States.

PMID- 9765108
TI  - A trial of tissue characterization by endoscopic ultrasonography.

PMID- 9765109
TI  - Clinical application of ultrasound 3 D imaging system in lesions of the
      gastrointestinal tract.
AB  - BACKGROUND AND STUDY AIMS: The usefulness of the ultrasound 3 D imaging system (3
      D-EUS) is reported. 3 D-EUS using an ultrasonic probe has been introduced as a
      result of the developments in 3 D-EUS (EU-IP) by Olympus. The 3 D-EUS image was
      reconstructed by composing the radial and linear images produced by 40 slices of
      radial image, which were obtained by spiral scanning of the ultrasonic probe in
      the sheath. This system also allowed numerous functions, such as multifreeze,
      high-resolution images, measurement etc. for a definitive diagnosis. RESULTS: In
      the past three years, 190 lesions of the gastrointestinal tract were examined by
      3 D-EUS. The rate of correct approach to the lesions was 89% (overall). The most
      inappropriate approach was a result of the oblique probe approach, or lesions
      sited in difficult positions. The radial, linear and 3 D images were generally
      good. Pulsation, deep attenuation and small lesions caused the worst images. Most
      small lesions were imaged thoroughly with radial imaging and so no significant
      changes can be seen with 3 D images. High-resolution images were more precise and
      finer than with plain EUS. CONCLUSIONS: 3 D-EUS contributed more useful and finer
      images for the EUS examinations. Gastrointestinal lesions are generally well
      displayed and recognizable. There are still a few problems to be solved for
      proper imaging, but there should be positive advances in diagnostic ability with
      the development of this system.

PMID- 9765110
TI  - The use of color Doppler EUS in gastrointestinal diseases.

PMID- 9765111
TI  - EUS-guided treatment with microwaves and HIFU.

PMID- 9765112
TI  - Indications for EUS-directed FNA.
AB  - EUS/FNA is an extremely precise method for sampling lesions surrounding the
      gastrointestinal tract. As experience widens, so do the indications for its use.
      However, as endoscopists explore ways to use this technique to improve patient
      care, a basic premise should be kept in mind: the information obtained should
      have the potential to affect patient management. There will undoubtedly be
      refinements in the application of EUS/FNA, but the future looks very promising
      indeed.

PMID- 9765113
TI  - EUS instruments for FNA.

PMID- 9765114
TI  - Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) in the USA.

PMID- 9765115
TI  - Endoscopic ultrasound-guided fine-needle biopsy in Europe.

PMID- 9765116
TI  - EUS-guided fine aspiration biopsy (FNA)--indications and hazards.
AB  - Ultrasound endoscopes with mechanical sector forward scan transducers make it
      possible to perform FNA under EUS, and drainage by tracing the needle in the
      ultrasound pictures by using the same monitor unit as for radial scan ultrasound
      endoscopes for EUS diagnosis. It is important to diagnose the lesions from the
      histological findings; however, there remain some problems about false negatives,
      histological diagnosis from very tiny materials, and the risk of disseminating
      the malignant cells by the procedure.

PMID- 9765117
TI  - Clinical impact of high-frequency ultrasound probe sonography during diagnostic
      endoscopy--a prospective study.

PMID- 9765118
TI  - Clinical implications of catheter probe-assisted endoluminal ultrasonography.

PMID- 9765119
TI  - Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for the diagnosis
      of digestive diseases.

PMID- 9765120
TI  - Preoperative endoscopic ultrasonography in decision making and management for
      pancreatic endocrine tumors: a 6-year experience.

PMID- 9765121
TI  - Optoelectronic monitoring of individual whisker movements in rats.
AB  - We describe two systems for the real-time recording and display of individual
      vibrissa movements in head-fixed rats. Both systems utilize high-speed, linear
      image sensors, each composed of an array of light sensitive elements (CCDs).
      Uniform illumination of the array generates a constant baseline voltage in each
      element. The shadow produced by the movement of a whisker interposed between the
      light source and the sensors produces a voltage shift in a subset of elements.
      The successive position of the shift is linearly related to the momentary whisker
      position. Associated software/hardware scans the array at regular intervals to
      identify the successive positions of voltages above a preset threshold and
      outputs the data to a microprocessor for computation of the whisker movement
      trajectory. In both systems, movements of a single whisker may be monitored 'on
      line' with high spatial and temporal resolution; in one case with, in the other
      without the presence of neighboring whiskers. Optoelectronic monitoring
      facilitates rapid and efficient (computer-assisted) acquisition and analysis of
      data on rodent whisking behavior.

PMID- 9765122
TI  - Reduction of background autofluorescence in brain sections following immersion in
      sodium borohydride.
AB  - Autofluorescence of aldehyde-fixed neural tissue often obscures perikaria and
      fine processes labeled with fluorescent anterograde or retrograde tracers. In
      particular, this autofluorescence hinders the detectability of fine axonal
      projections labeled with the convenient anterograde tracer, tetramethylrhodamine
      dextranamine. Background fluorescence was notably reduced by immersion of free
      floating brain tissue sections in a solution of sodium borohydride (NaBH4, 0.1%),
      a chemical which is known to neutralize Schiffs bases through reduction of amine
      aldehyde compounds into non-fluorescent salts. The reversible and renewable
      immersion technique was most effective in paraformaldehyde-fixed tissue where the
      preservation quality was improved such that labeled axons remained detectable for
      more than 1 year after initial preparation.

PMID- 9765123
TI  - Characterization of [125I-Tyr0]-corticotropin releasing factor (CRF) binding to
      the CRF binding protein using a scintillation proximity assay.
AB  - We describe the characterization of high affinity [125I-Tyr0]-human CRF binding
      to purified recombinant human CRF-binding protein (CRF-BP) using a scintillation
      proximity assay (SPA). For this stable nonseparation technique developed in 96
      well microtiter plates, biotinylated CRF-BP is captured by streptavidin-coated
      SPA beads for the detection of bound [125I-Tyr0]-CRF. Unbound [125I-Tyr0]-CRF
      represented little or no signal in the assay. Total binding observed was greater
      than 5000 cpm with a nonspecific signal of < 100 cpm determined in the presence
      of excess unlabeled human CRF. A comparison of the SPA method with a charcoal
      precipitation method confirmed that the biotinylation procedure did not adversely
      affect affinity of the CRF-BP for [125I-Tyr0]-CRF. Saturation binding analysis
      yielded an apparent equilibrium dissociation constant (Kd) of 208 +/- 5.0 pM (+/-
      S.D., n = 3). An inhibition constant (Ki) for unlabeled CRF was calculated to be
      0.22 +/- 0.03 nM (+/- S.D., n = 8) and a pharmacological profile for eight CRF
      related neuropeptides gave a rank potency similar to previously reported results.
      Finally, the assay variability was assessed with intra- and inter-plate
      coefficients of variation which were less than 5% each.

PMID- 9765124
TI  - Combined methods of retrograde staining, layer-separation and viscoelastic cell
      stabilization to isolate retinal ganglion cells in adult rats.
AB  - The adult retinal ganglion cells (RGCs) are widely used as a model to study
      mechanisms of de- and regeneration within the central nervous system (CNS). All
      regions of the CNS including the retina have the common disadvantage of being
      composed of heterogeneous populations of cells, many of them like RGCs making
      less than 1% of the total population. This disadvantage can be circumvented by
      methodologies aimed at purifying specific cell types. Here we describe a method
      that combines retrograde labelling with fluorescent dyes and the pull-off
      technique. By using either of four different fluorescent dyes to retrogradely
      label RGCs, between 55 and 80% of pre-labelled ganglion cells could be identified
      with fluorescence microscopy. The pull-off procedure was supplemented by
      enhancing the viscosity of the collecting medium with methylhydroxypropyl
      cellulose (MHPC). It appeared that 45% of all RGCs could be collected in the
      medium containing MHPC as compared to about 19% of RGCs which could be collected
      in medium devoid of cellulose. Despite the fact that morphometric measurements
      indicated that 60% of the cells collected fulfilled the criteria of being RGCs,
      the population obtained was immensely enriched and sufficed to perform a two
      dimensional SDS-gel electrophoresis and to determine their protein composition.
      The collected RGCs displayed a similar protein pattern as compared to that of the
      total retina, indicating that sublayers of the retina were represented in the
      probe. The results suggest that combined approaches of in vivo staining and ex
      vivo separation within suitable media enables the collection of an enriched
      population of cells which can be processed for biochemical analysis, and perhaps
      for molecular biology.

PMID- 9765125
TI  - Using miniature sensor coils for simultaneous measurement of orientation and
      position of small, fast-moving animals.
AB  - A system is described that measures, with a sampling frequency of 1 kHz, the
      orientation and position of a blowfly (Calliphora vicina) flying in a volume of
      0.4 x 0.4 x 0.4 m3. Orientation is measured with a typical accuracy of 0.5
      degrees, and position with a typical accuracy of 1 mm. This is accomplished by
      producing a time-varying magnetic field with three orthogonal pairs of field
      coils, driven sinusoidally at frequencies of 50, 68, and 86 kHz, respectively.
      Each pair induces a voltage at the corresponding frequency in each of three
      miniature orthogonal sensor coils mounted on the animal. The sensor coils are
      connected via thin (12-microm) wires to a set of nine lock-in amplifiers, each
      locking to one of the three field frequencies. Two of the pairs of field coils
      produce approximately homogeneous magnetic fields, which are necessary for
      reconstructing the orientation of the animal. The third pair produces a gradient
      field, which is necessary for reconstructing the position of the animal. Both
      sensor coils and leads are light enough (0.8-1.6 mg for three sensor coils of 40
      80 windings, and 6.7 mg/m for the leads, causing a maximal load of approximately
      5.7 mg) not to hinder normal flight of the animal (typical weight 80 mg). In
      general, the system can be used for high-speed recordings of head, eye or limb
      movements, where a wire connection is possible, but the mechanical load on the
      moving parts needs to be very small.

PMID- 9765126
TI  - A dicistronic retroviral vector and culture model for analysis of neuron-Schwann
      cell interactions.
AB  - A dicistronic retroviral gene delivery system and tissue culture model has been
      developed for studies of neuron-Schwann cell interactions at the single cell
      level. The dicistronic retroviral vector contains a multiple cloning site
      followed by the encephalomyocarditis virus internal ribosomal entry site (EMCV
      IRES) and a green fluorescent protein gene. This design allows for 5'-cap
      dependent translation of any gene of interest and 5'-cap independent translation
      of green fluorescent protein (GFP) from a single dicistronic RNA. The culture
      model consists of dorsal root ganglia (DRG) explants grown in defined medium.
      Under these conditions the Schwann cell population is selectively expanded and
      infected by the retroviral vector, allowing for rapid transfer of genes of
      interest selectively to a large percentage of Schwann cells in coculture with
      neurons. Infected cells are subsequently identified in living cultures by their
      expression of GFP. Infected (GFP expressing) Schwann cells in contact with
      neurites continued to exhibit: (1) increased mitotic activity, (2) increased
      sensitivity to elevate intracellular calcium in response to extracellular
      application of ATP, and (3) myelination. This viral construct has the added
      advantage that it allows identification of cells expressing transgenes among a
      heterogeneous population by fluorescence microscopy, FACS, or flow cytometry.

PMID- 9765127
TI  - Simultaneous determination of acetylcholine, choline and physostigmine in
      microdialysis samples from rat hippocampus by microbore liquid
      chromatography/electrochemistry on peroxidase redox polymer coated electrodes.
AB  - Microbore column liquid chromatography with post-column immobilized enzyme
      reactor (IMER) and electrochemical detection on redox polymer coated electrodes
      was used for detection of acetylcholine (ACh) and choline (Ch) in microdialysis
      samples. The sensitivity of the coated electrodes, decreased gradually by about
      10%/day, with highest reduction of 30% within the first 16 h of use. A number of
      choline derivatives were tested as possible internal standards, of those
      acetylethylhomocholine (AEHCh) and butyrylcholine (BCh) were found the most
      suitable candidates since they both provided high enzymatic conversion in the
      IMER. Physostigmine produced a negative peak, possibly reflecting oxidation of
      eseroline--a decarbamoylated product of reversible reaction of physostigmine with
      immobilized acetylcholine esterase. The probes, implanted in the ventral
      hippocampi of awake rats were perfused at a flow-rate of 1.25 microl/min with
      Ringer solution containing 10 microM physostigmine or with artificial
      cerebrospinal fluid only. The concentrations of ACh in 10-microl samples at basal
      conditions were between 0.9-2.5 nM, whereas in the presence of physostigmine the
      ACh levels raised to 41-48 nM. Physostigmine concentration was reduced to 8.8
      microM, indicating its in vivo delivery of about 12%. The coefficients of
      variation were reduced from 7.4% for external standard method after every sixth
      sample to 5.8% and 5.9% for internal standardization with AEHCh and BCh,
      respectively. The latter method shortened the total analysis time by about 15%,
      thus being especially suitable for continuous long-lasting off-line or on-line
      monitoring. Additionally, other endogenous cholines such as butyrylcholine or
      synthetic choline derivatives could be detected by the present method.

PMID- 9765128
TI  - Stroke assessment: morphometric infarct size versus neurologic deficit.
AB  - We presently examine the relation between histologic infarct size and neurologic
      deficit as endpoints and seek to clarify their sensitivity in defining stroke
      outcome. Neurologic deficits of 76 cats subjected to middle cerebral artery
      occlusion were assessed daily and correlated with the corresponding infarct sizes
      determined morphometrically after 2 weeks' survival. A five-item neurologic
      deficit score included the time elapsed until hemiparesis, and forced circling
      resolved (if ever), presence of impaired placing reactions and time elapsed until
      able to stand and being alert. We then evaluated the two endpoints' statistical
      powers to detect group differences using two sets of comparison groups. The
      neurologic deficit score correlated well with infarct size (r = 0.76, p < 0.001)
      and each of the individual deficit score components named above, in turn,
      correlated with decreasing power with infarct size. Even so, the number of study
      subjects required to achieve the same level of statistical significance in
      assessing group differences was two-fold greater when using the neurologic
      deficit than the infarct size data: Group sizes of eight and five animals were
      sufficient for significant infarct size differences while the groups needed be
      expanded to 15 and 10 animals to similarly achieve significant neurologic score
      differences. Thus, infarct size emerges as a more sensitive measure of stroke
      outcome than does the assessment of neurologic deficits.

PMID- 9765129
TI  - Luciferase: a sensitive and quantitative probe for blood-brain barrier
      disruption.
AB  - A novel method for quantitative analysis of blood-brain barrier (BBB) disruption
      is described, using luciferase as a probe in a murine model system. Purified
      luciferase was delivered to mouse brain by osmotic BBB disruption with hypertonic
      mannitol; control animals received an intracarotid inoculation of saline prior to
      infusion of luciferase. Delivery of luciferase to brain tissue was then assessed
      by enzyme assay of tissue extracts, and by immunohistochemical staining.
      Luciferase activity in the brain of mannitol-treated animals was found to be
      significantly elevated (approx. sevenfold), when compared to activity in control
      (saline-treated) mice. This finding was confirmed by quantitative
      immunohistochemical staining of tissue sections, using a luciferase-specific
      antibody. These studies showed that there was an eight-fold elevation in the
      level of extravascular luciferase particles within the brain of mannitol-treated
      animals, as compared to controls. Taken together these data show that purified
      recombinant luciferase can be used as a sensitive probe, with which to study the
      integrity of the BBB.

PMID- 9765130
TI  - The overall rod performance test in the MPTP-treated-mouse model of Parkinsonism.
AB  - We investigated the usefulness of the Overall Rotarod Performance (ORP) test for
      evaluating overall locomotory ability in the 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP)-injected-mouse model of Parkinson's disease (PD). For
      this procedure, the mice are pretrained on the rotarod and then tested at a
      series of increasing speeds, recording the time that the animal remains on the
      rod at each speed; the overall rod performance (ORP) of each animal is then
      calculated as the area under the curve in a plot of time-on-the-rod against
      rotation speed. At 15-day intervals, C57BL/6 mice were injected (or sham
      injected) with MPTP, with ORP testing 7-10 days after each injection. After the
      fourth injection (day 45), mice in the treated group showed clearly lower ORP
      than mice in the control group (70-90% reduction in ORP), and were thus
      considered effectively lesioned. Subsequently, we investigated the short-term
      effects of apomorphine and L-DOPA on ORP in MPTP-treated mice. Apomorphine (at
      0.5 or 2.5 mg/kg) had no significant effect, while L-DOPA (at 80 but not at 40
      mg/kg) caused almost complete short-term recovery of pretreatment ORP. By about
      100 days after the last MPTP injection, MPTP-treated mice showed partial long
      term recovery of ORP; at this stage the mice were killed for tyrosine hydroxylase
      (TH) immunohistochemistry studies. TH immunoreactivity in the striatum showed a
      strong positive correlation with ORP as tested on day 100. We conclude that the
      ORP test is useful for evaluating motor deficit in MPTP-treated mice, and the
      effects of subsequent treatments.

PMID- 9765131
TI  - A simple, low-cost and fast Peltier thermoregulation set-up for
      electrophysiology.
AB  - Most of the parameters recorded in electrophysiology are strongly temperature
      dependent. In order to control temperature fluctuations we have built a system
      that ensures an accurate thermoregulation of the recording chamber. Temperature
      of physiological preparations can be changed relatively quickly (about 8 degrees
      C/min) and with a good accuracy (+/- 0.5 degrees C) without inducing thermal
      oscillations. Contrary to other thermoregulating devices, the temperature
      regulation is not carried out through the perfused medium but directly at the
      bottom of the chamber where a 3-cm2 Peltier element has been placed. The element
      is driven by a dedicated electronic device which controls the amount and the
      direction of the current flowing across the Peltier thermocouple. All
      construction details and the appropriate electrical circuits are provided. Using
      this home-made device, the steady-state chamber temperature could be precisely
      monitored with a resolution of +/- 0.1 degrees C in a range of 0-40 degrees C.
      This set-up was tested in experiments designed to evaluate the temperature
      dependence of synaptic transmission in the Torpedo nerve electroplate synapses
      and of calcium currents recorded from isolated nerve cells. This low-cost method
      is suitable for a wide range of applications.

PMID- 9765132
TI  - Estimating stimulus response latency.
AB  - Stimulus response latency is the delay in the onset of stimulus-evoked neuronal
      activity. We develop maximum likelihood and least squares estimators of stimulus
      response latency and present a comparison of the performance of these methods
      with estimators commonly used in the neuroscience literature. The formal
      statistical change-point estimation problem is nontrivial due to the inclusion of
      a 'nuisance parameter', the end of stationarity in the stimulus-evoked activity.
      Our results suggest that the automation of the estimation of stimulus response
      latency will benefit from the use of the maximum likelihood estimator.

PMID- 9765133
TI  - Disorders of the hallux sesamoid complex: MR features.
AB  - Numerous painful conditions can affect the first metatarsophalangeal-sesamoid
      joint complex. Symptoms can be of sudden or insidious onset, and be of acute or
      chronic duration. Although conventional radiography is recognized as the initial
      diagnostic procedure for these symptoms, there is often a need to proceed to MR
      imaging. MR imaging is sensitive and can be utilized in the investigation of the
      hallux sesamoid complex to differentiate soft tissue from osseous pathology.
      Synovitis, tendonitis, and bursitis can be distinguished from bony abnormalities
      such as sesamoid fracture, avascular necrosis, and osteomyelitis. An
      understanding of MR imaging features and techniques will result in the highest
      diagnostic yield. Early and accurate diagnosis of sesamoid complex disorders can
      guide the physician to the appropriate clinical management and prevent
      potentially harmful longstanding joint dysfunction.

PMID- 9765134
TI  - MR imaging of the major nerves about the elbow: cadaveric study examining the
      effect of flexion and extension of the elbow and pronation and supination of the
      forearm.
AB  - Magnetic resonance (MR) imaging provides useful information in the evaluation of
      peripheral nerves. Recent advances in MR imaging allow for detailed depiction of
      the soft tissue structures of the elbow joint. Three major nerves are present
      about the elbow. Six cadaveric elbows were imaged to depict the normal anatomy of
      these nerves and to determine the best plane and position of the elbow for
      optimal visualization of each nerve. Axial images of the elbow in full extension
      with the forearm in supination allow identification of all major nerves. Axial
      images with the elbow in full flexion allow accurate assessment of the cubital
      tunnel and the ulnar nerve. Axial images of the elbow in full extension with the
      forearm in pronation are helpful for assessment of the median and radial nerves
      in the forearm.

PMID- 9765135
TI  - MR imaging of symptomatic osteochondromas with pathological correlation.
AB  - OBJECTIVE: To demonstrate the value of MR imaging in the diagnosis and
      differentiation of the various symptomatic complications of osteochondromas,
      providing pathological correlation with emphasis on the usefulness of MR imaging
      as a single imaging modality in these patients. DESIGN: We retrospectively
      reviewed all MR examinations of clinically symptomatic osteochondromas (30
      patients) performed at our institution between March 1990 and October 1997.
      PATIENTS: Thirty patients had clinically symptomatic osteochondromas during the
      study period. Twenty patients were male and 10 were female. There were five cases
      of multiple osteochondromatosis. Pathological correlation was available in 24
      patients. RESULTS AND CONCLUSION: Symptomatic complications included fracture
      (7%), osseous deformity limiting range of motion (23%), vascular injury (7%),
      neurological compromise (10%), bursa formation (27%) and malignant transformation
      (27%). MR imaging was able to diagnose or suggest the etiology for the clinical
      symptomatology in all cases, demonstrating that it is an ideal imaging modality
      in the diagnostic evaluation of symptomatic complications of osteochondromas and
      often avoids the need for further imaging.

PMID- 9765136
TI  - Internal derangement of the knee after ipsilateral femoral shaft fracture: MR
      imaging findings.
AB  - OBJECTIVE: This study uses magnetic resonance (MR) imaging to delineate the types
      and frequencies of injuries seen in the knee after ipsilateral femoral shaft
      fracture. We also compare the results of the orthopedic knee examination with the
      MR findings. DESIGN AND PATIENTS: MR imaging of the ipsilateral knee was
      performed on 34 patients with closed femoral shaft fractures. Indications for
      knee MR imaging included knee pain at the time of fracture, soft tissue swelling
      or an effusion of the knee, or a positive knee examination under anesthesia. The
      patients had a mean age of 27 years and all were stabilized with intramedullary
      nails. Imaging was performed a mean time of 2.5 days after surgery. All patients
      had knee examinations done under anesthesia, and the MR results were compiled and
      compared with the clinical examinations. RESULTS: Ninety-seven percent of
      patients demonstrated knee effusions. Twenty-seven percent of patients
      demonstrated meniscal tears, with the posterior horn of the medial meniscus most
      frequently torn. The medial collateral ligament was the most frequent site of
      ligamentous injury (38%) followed by the posterior cruciate ligament (21%). Fifty
      percent of patients had injuries of the extensor mechanism. Bone bruises were
      noted in 32% of patients. Articular cartilage injuries were confined to the
      patella in four cases. One occult tibial plateau fracture and one meniscocapsular
      separation were seen. CONCLUSIONS: There is a common incidence of both
      ligamentous and meniscal injury to the knee after ipsilateral femoral shaft
      fracture. MR imaging can be useful in assessing the extent of injury, and may
      reveal findings unsuspected after clinical examination of the knee.

PMID- 9765137
TI  - Tarsal navicular relations in club foot: is there a role for magnetic resonance
      imaging?
AB  - OBJECTIVE: To correlate radiographic and MR appearances with surgical findings to
      determine the accuracy of these modalities in demonstrating tarsal navicular (TN)
      relations in order to select the appropriate surgical intervention. DESIGN AND
      PATIENTS: Fourteen consecutive patients with 19 club feet had anteroposterior and
      lateral radiographs and magnetic resonance (MR) imaging performed. Blinded
      retrospective interpretation of these studies was correlated with surgical
      findings. Movement artifact was responsible for initial non-diagnostic MR scans
      in 3 out of 19 feet. RESULTS: Plain radiographs and MR imaging had sensitivities
      of 79% and 84% respectively for TN subluxation, while both modalities had 100%
      positive predictive value for TN subluxation. Each modality produced
      indeterminate results in cases where subluxation was present at surgery, but in
      combination there were no false negatives. CONCLUSION: Radiography confidently
      predicted the TN alignment in the majority of cases. MR demonstrated TN
      relationships in all cases where radiography was indeterminate. It is proposed
      that MR has a potential role to demonstrate TN relationships when radiography is
      indeterminate or when there is disparity between the clinical and radiographic
      assessment.

PMID- 9765138
TI  - Sclerotic variant of lymphangiomatosis of bone: imaging findings at diagnosis and
      long-term follow-up.
AB  - Lymphangiomatosis is an extremely rare congenital disorder affecting visceral
      organs and/or the skeletal system. In bone is is usually characterized by
      multiple lytic lesions with a lacelike pattern and sclerotic margins of various
      thickness. In this case report we demonstrate the rare sclerotic variant of
      lymphangiomatosis. We report the development of predominantly sclerotic lesions
      at different sites by serial radiographs with a long-term follow-up, and show the
      MRI findings of lymphangiomatosis of the spine.

PMID- 9765139
TI  - Bifocal sclerosing osteosarcoma: unusual presentation and course.
AB  - Multifocal osteosarcoma is uncommon. Long-term survival of an incompletely
      treated case is exceptional. We report an unusual case of bifocal sclerosing
      osteosarcoma in a 38-year-old women that involved the left ilium and right
      proximal femur. The femoral lesion was resected. The tumor in the left ilium was
      not treated. She did not receive chemotherapy and has been free of metastases for
      7 years. Recently, growth of the pelvic osteosarcoma has resulted in vascular
      compression and edema of the lower extremity. The patient's alkaline phosphatase
      has been elevated throughout. The tumor was HMB-45 positive, which has not been
      previously reported in osteosarcoma. The pathogenesis of multifocal osteosarcoma
      is discussed.

PMID- 9765140
TI  - Intraarticular epithelioid sarcoma.
AB  - A case of an intraarticular epithelioid sarcoma is presented. The patient was a
      35 year old man who presented with a 10 months history of a chronic
      monoarthritis. The MRI showed a diffuse lesion involving the synovial membrane of
      the knee. There was a marked increased signal on T2 weighted images. Most
      epithelioid sarcomas involve the subcutaneous tissues of the hands or feet. This
      presentation is unusual and this entity should be considered in the differential
      diagnosis of an intraarticular proliferative process.

PMID- 9765141
TI  - Rheumatoid nodule of the foot: MRI appearances mimicking an indeterminate soft
      tissue mass.
AB  - Subcutaneous rheumatoid nodules occur commonly in advanced cases of rheumatoid
      arthritis, but only rarely appear in the feet. We present a case of a
      subcutaneous rheumatoid nodule arising in the heel pad of a 68-year-old man with
      a long history of rheumatoid arthritis, along with a review of the literature.
      The appearance of the mass on MRI is illustrated and correlated with the
      histologic findings. The MRI appearance of a subcutaneous rheumatoid nodule is
      that of a nonspecific ill-defined mass with long T1- and long T2-relaxation
      times. A differential diagnosis for similar appearing masses is offered.

PMID- 9765142
TI  - Epiphyseal separation of the coracoid process without acromioclavicular
      dislocation.
AB  - A patient with an epiphyseal separation through the base of the coracoid process
      of the shoulder associated with a grade I acromioclavicular sprain is reported.
      The epiphyseal separation was not visible on conventional roentgenograms. A CT
      scan demonstrated the abnormality. In patients with considerable intractable pain
      due to contusion of the shoulder, early use of CT should be considered to
      determine whether symptoms are caused by epiphyseal separation of the coracoid
      process.

PMID- 9765143
TI  - Malignant fibrous histiocytoma associated with a bone infarct in a patient with
      hereditary bone dysplasia.
AB  - Hereditary bone dysplasia (HBD) is an extremely rare clinicopathological entity
      manifested by diaphyseal medullary stenosis and cortical bone thickening
      associated with a propensity for fractures affecting the long tubular bone.
      Malignant transformation has been reported to occur at an alarming frequency. The
      hereditary pattern appears to be autosomal dominant. In this paper we present the
      case of a 19-year-old man with hereditary bone dysplasia who was unaware of his
      underlying condition until he presented with malignant transformation arising in
      an area of bone infarct of the left tibia.

PMID- 9765144
TI  - Extragnathic fibromyxoma of bone versus inflammatory myofibroblastic tumor.

PMID- 9765145
TI  - The chemistry of water on alumina surfaces: reaction dynamics from first
      principles 
AB  - Aluminas and their surface chemistry play a vital role in many areas of modern
      technology. The behavior of adsorbed water is particularly important and poorly
      understood. Simulations of hydrated alpha-alumina (0001) surfaces with ab initio
      molecular dynamics elucidate many aspects of this problem, especially the complex
      dynamics of water dissociation and related surface reactions. At low water
      coverage, free energy profiles established that molecularly adsorbed water is
      metastable and dissociates readily, even in the absence of defects, by a
      kinetically preferred pathway. Observations at higher water coverage revealed
      rapid dissociation and unanticipated collective effects, including water
      catalyzed dissociation and proton transfer reactions between adsorbed water and
      hydroxide. The results provide a consistent interpretation of the measured
      coverage dependence of water heats of adsorption, hydroxyl vibrational spectra,
      and other experiments.

PMID- 9765146
TI  - Past temperatures directly from the greenland ice sheet 
AB  - A Monte Carlo inverse method has been used on the temperature profiles measured
      down through the Greenland Ice Core Project (GRIP) borehole, at the summit of the
      Greenland Ice Sheet, and the Dye 3 borehole 865 kilometers farther south. The
      result is a 50, 000-year-long temperature history at GRIP and a 7000-year history
      at Dye 3. The Last Glacial Maximum, the Climatic Optimum, the Medieval Warmth,
      the Little Ice Age, and a warm period at 1930 A.D. are resolved from the GRIP
      reconstruction with the amplitudes -23 kelvin, +2.5 kelvin, +1 kelvin, -1 kelvin,
      and +0.5 kelvin, respectively. The Dye 3 temperature is similar to the GRIP
      history but has an amplitude 1.5 times larger, indicating higher climatic
      variability there. The calculated terrestrial heat flow density from the GRIP
      inversion is 51.3 milliwatts per square meter.

PMID- 9765147
TI  - Direct measurement of femtomoles of osmium and the 187Os/186Os ratio in seawater 
AB  - Two depth profiles of the osmium concentration and the 187Os/186Os isotopic ratio
      in the Indian Ocean showed that the osmium concentration seems to be unaltered by
      chemical or biological processes occuring in seawater; accordingly, osmium is
      conservative. These data were obtained from an experimental method that
      eliminated the problems related to osmium preconcentration. This method led to a
      new evaluation of the concentration of osmium in seawater; the mean concentration
      of osmium and the 187Os/186Os ratio are equal to 10.86 +/- 0.07 picograms per
      kilogram and 8.80 +/- 0.07, respectively. The results suggest the existence of an
      organocomplex that dominates the speciation of osmium in seawater.

PMID- 9765148
TI  - Experimental demonstration of guiding and bending of electromagnetic waves in a
      photonic crystal 
AB  - The routing and interconnection of optical signals through narrow channels and
      around sharp corners are important for large-scale all-optical circuit
      applications. A recent computational result suggests that photonic crystals may
      offer a novel way of achieving this goal by providing a mechanism for guiding
      light that is fundamentally different from traditional index guiding. Waveguiding
      in a photonic crystal and near 100 percent transmission of electromagnetic waves
      around sharp 90 degree corners were observed experimentally. Bending radii were
      made smaller than one wavelength.

PMID- 9765149
TI  - Organic carbon fluxes and ecological recovery from the cretaceous-tertiary mass
      extinction 
AB  - Differences between the carbon isotopic values of carbonates secreted by planktic
      and benthic organisms did not recover to stable preextinction levels for more
      than 3 million years after the Cretaceous-Tertiary mass extinction. These
      decreased differences may have resulted from a smaller proportion of marine
      biological production sinking to deep water in the postextinction ocean. Under
      this hypothesis, marine production may have recovered shortly after the mass
      extinction, but the structure of the open-ocean ecosystem did not fully recover
      for more than 3 million years.

PMID- 9765150
TI  - Climate change record in subsurface temperatures: A global perspective 
AB  - Analyses of underground temperature measurements from 358 boreholes in eastern
      North America, central Europe, southern Africa, and Australia indicate that, in
      the 20th century, the average surface temperature of Earth has increased by about
      0.5 degreesC and that the 20th century has been the warmest of the past five
      centuries. The subsurface temperatures also indicate that Earth's mean surface
      temperature has increased by about 1.0 degreesC over the past five centuries. The
      geothermal data offer an independent confirmation of the unusual character of
      20th-century climate that has emerged from recent multiproxy studies.

PMID- 9765151
TI  - Isolation of acidophilic methane-oxidizing bacteria from northern peat wetlands.
AB  - Acidic northern wetlands are an important source of methane, one of the gases
      that contributes to global warming. Methane oxidation in the surface of these
      acidic wetlands can reduce the methane flux to the atmosphere up to 90 percent.
      Here the isolation of three methanotrophic microorganisms from three boreal
      forest sites is reported. They are moderately acidophilic organisms and have a
      soluble methane monooxygenase. In contrast to the known groups of methanotrophs,
      16S ribosomal DNA sequence analysis shows that they are affiliated with the
      acidophilic heterotrophic bacterium Beijerinckia indica subsp. indica.

PMID- 9765152
TI  - Alterations of the PPP2R1B gene in human lung and colon cancer.
AB  - The PPP2R1B gene, which encodes the beta isoform of the A subunit of the
      serine/threonine protein phosphatase 2A (PP2A), was identified as a putative
      human tumor suppressor gene. Sequencing of the PPP2R1B gene, located on human
      chromosome 11q22-24, revealed somatic alterations in 15% (5 out of 33) of primary
      lung tumors, 6% (4 out of 70) of lung tumor-derived cell lines, and 15% (2 out of
      13) of primary colon tumors. One deletion mutation generated a truncated PP2A
      Abeta protein that was unable to bind to the catalytic subunit of the PP2A
      holoenzyme. The PP2R1B gene product may suppress tumor development through its
      role in cell cycle regulation and cellular growth control.

PMID- 9765153
TI  - Role of farnesyltransferase in ABA regulation of guard cell anion channels and
      plant water loss.
AB  - Desiccation of plants during drought can be detrimental to agricultural
      production. The phytohormone abscisic acid (ABA) reduces water loss by triggering
      stomatal pore closure in leaves, a process requiring ion-channel modulation by
      cytoplasmic proteins. Deletion of the Arabidopsis farnesyltransferase gene ERA1
      or application of farnesyltransferase inhibitors resulted in ABA hypersensitivity
      of guard cell anion-channel activation and of stomatal closing. ERA1 was
      expressed in guard cells. Double-mutant analyses of era1 with the ABA-insensitive
      mutants abi1 and abi2 showed that era1 suppresses the ABA-insensitive phenotypes.
      Moreover, era1 plants exhibited a reduction in transpirational water loss during
      drought treatment.

PMID- 9765154
TI  - Cell surface trafficking of Fas: a rapid mechanism of p53-mediated apoptosis.
AB  - p53 acts as a tumor suppressor by inducing both growth arrest and apoptosis. p53
      induced apoptosis can occur without new RNA synthesis through an unknown
      mechanism. In human vascular smooth muscle cells, p53 activation transiently
      increased surface Fas (CD95) expression by transport from the Golgi complex.
      Golgi disruption blocked both p53-induced surface Fas expression and apoptosis.
      p53 also induced Fas-FADD binding and transiently sensitized cells to Fas-induced
      apoptosis. In contrast, lpr and gld fibroblasts were resistant to p53-induced
      apoptosis. Thus, p53 can mediate apoptosis through Fas transport from cytoplasmic
      stores.

PMID- 9765155
TI  - Bifurcation of lipid and protein kinase signals of PI3Kgamma to the protein
      kinases PKB and MAPK.
AB  - Phosphoinositide 3-kinases (PI3Ks) activate protein kinase PKB (also termed Akt),
      and PI3Kgamma activated by heterotrimeric guanosine triphosphate-binding protein
      can stimulate mitogen-activated protein kinase (MAPK). Exchange of a putative
      lipid substrate-binding site generated PI3Kgamma proteins with altered or aborted
      lipid but retained protein kinase activity. Transiently expressed, PI3Kgamma
      hybrids exhibited wortmannin-sensitive activation of MAPK, whereas a
      catalytically inactive PI3Kgamma did not. Membrane-targeted PI3Kgamma
      constitutively produced phosphatidylinositol 3,4, 3,4,5-trisphosphate and
      activated PKB but not MAPK. Moreover, stimulation of MAPK in response to
      lysophosphatidic acid was blocked by catalytically inactive PI3Kgamma but not by
      hybrid PI3Kgammas. Thus, two major signals emerge from PI3Kgamma:
      phosphoinositides that target PKB and protein phosphorylation that activates
      MAPK.

PMID- 9765156
TI  - Controlling gene expression in living cells through small molecule-RNA
      interactions.
AB  - Short RNA aptamers that specifically bind to a wide variety of ligands in vitro
      can be isolated from randomized pools of RNA. Here it is shown that small
      molecule aptamers also bound their ligand in vivo, enabling development of a
      method for controlling gene expression in living cells. Insertion of a small
      molecule aptamer into the 5' untranslated region of a messenger RNA allowed its
      translation to be repressible by ligand addition in vitro as well as in mammalian
      cells. The ability of small molecules to control expression of specific genes
      could facilitate studies in many areas of biology and medicine.

PMID- 9765157
TI  - Transition from moderate to excessive drug intake: change in hedonic set point.
AB  - Differential access to cocaine self-administration produced two patterns of drug
      intake in rats. With 1 hour of access per session, drug intake remained low and
      stable. In contrast, with 6 hours of access, drug intake gradually escalated over
      days. After escalation, drug consumption was characterized by an increased early
      drug loading and an upward shift in the cocaine dose-response function,
      suggesting an increase in hedonic set point. After 1 month of abstinence,
      escalation of cocaine intake was reinstated to a higher level than before. These
      findings may provide an animal model for studying the development of excessive
      drug intake and the basis of addiction.

PMID- 9765159
TI  - The teenager with epilepsy. Has special needs.

PMID- 9765158
TI  - Puzzling out priorities. Why we must acknowledge that rationing is a political
      process.

PMID- 9765160
TI  - Dying from heart failure: lessons from palliative care. Many patients would
      benefit from palliative care at the end of their lives.

PMID- 9765162
TI  - Psychiatry, stigma, and resistance. Psychiatrists need to concentrate on
      understanding, not simply compliance.

PMID- 9765161
TI  - Smoking and stroke: a causative role. Heavy smokers with hypertension benefit
      most from stopping.

PMID- 9765163
TI  - Repositioning self regulation. The influence of the GMC may be leaking away.

PMID- 9765164
TI  - Should inhaled anticholinergics be added to beta2 agonists for treating acute
      childhood and adolescent asthma? A systematic review.
AB  - OBJECTIVES: To estimate the therapeutic and adverse effects of addition of
      inhaled anticholinergics to beta2 agonists in acute asthma in children and
      adolescents. DESIGN: Systematic review of randomised controlled trials of
      children and adolescents taking beta2 agonists for acute asthma with or without
      the addition of inhaled anticholinergics. MAIN OUTCOME MEASURES: Hospital
      admission, pulmonary function tests, number of nebulised treatments, relapse, and
      adverse effects. RESULTS: Of 37 identified trials, 10 were relevant and six of
      these were of high quality. The addition of a single dose of anticholinergic to
      beta2 agonist did not reduce hospital admission (relative risk 0.93, 95%
      confidence interval 0.65 to 1.32). However, significant group differences in lung
      function supporting the combination treatment were observed 60 minutes
      (standardised mean difference -0.57, -0.93 to -0.21) and 120 minutes (-0.53, 
      0.90 to -0.17) after the dose of anticholinergic. In contrast, the addition of
      multiple doses of anticholinergics to beta2 agonists, mainly in children and
      adolescents with severe exacerbations, reduced the risk of hospital admission by
      30% (relative risk 0.72, 0.53 to 0.99). Eleven (95% confidence interval 5 to 250)
      children would need to be treated to avoid one admission. A parallel improvement
      in lung function (standardised mean difference -0.66, -0.95 to -0.37) was noted
      60 minutes after the last combined inhalation. In the single study where
      anticholinergics were systematically added to every beta2 agonist inhalation,
      irrespective of asthma severity, no group differences were observed for the few
      available outcomes. There was no increase in the amount of nausea, vomiting, or
      tremor in patients treated with anticholinergics. CONCLUSIONS: Adding multiple
      doses of anticholinergics to beta2 agonists seems safe, improves lung function,
      and may avoid hospital admission in 1 of 11 such treated patients. Although
      multiple doses should be preferred to single doses of anticholinergics, the
      available evidence only supports their use in school aged children and
      adolescents with severe asthma exacerbation.

PMID- 9765165
TI  - Cold related mortalities and protection against cold in Yakutsk, eastern Siberia:
      observation and interview study.
AB  - OBJECTIVE: To assess how effectively measures adopted in extreme cold in Yakutsk
      control winter mortality. DESIGN: Interviews to assess outdoor clothing and
      measure indoor temperatures; regressions of these and of delayed cause-specific
      mortalities on temperature. Setting Yakutsk, east Siberia, Russia. SUBJECTS: All
      people aged 50-59 and 65-74 years living within 400 km of Yakutsk during 1989-95
      and sample of 1002 men and women who agreed to be interviewed. MAIN OUTCOME
      MEASURES: Daily mortality from all causes and from ischaemic heart,
      cerebrovascular, and respiratory disease. RESULTS: Mean temperature for October
      March 1989-95 was -26.6 degreesC. At 10.2 degrees C people wore 3.30 (95%
      confidence interval 3.08 to 3.53) layers of clothing outdoors, increasing to 4.39
      (4.13 to 4.66; P<0. 0001) layers at -20 degrees C. Thick coats, often of fur,
      replaced anoraks as temperature fell to -48.2 degrees C. 82% of people went out
      each day when temperatures were 10.2 degrees C to -20 degrees C, but below -20
      degrees C the proportion fell steadily to 44% (35% to 53%) at -48.2 degrees C
      (P<0.001), and overall shivering outdoors did not increase. Living room
      temperature was 17.9 (17.2 to 18.5) degrees C at 10.2 degrees C outdoors, 19.6
      (18.8 to 20.4) degrees C at -20 degrees C, and 19.1 (18.6 to 19.6) degrees C at 
      48.2 degrees C. Mortality from all causes and from ischaemic heart and
      respiratory disease was unaffected by the fall in temperature. Mortality from
      respiratory disease (daily deaths per million) rose from 4.7 (4.3 to 5.1) to 5.1
      (4.4 to 5.7) (P=0.03), but this was offset by a fall in deaths from injury.
      CONCLUSIONS: People in Yakutsk wore very warm clothing, and in extremely cold
      weather stayed indoors in warm housing, preventing the increases in mortality
      seen in winter in milder regions of the world. Only respiratory mortality rose,
      perhaps because of breathing cold air.

PMID- 9765166
TI  - Severe deep white matter lesions and outcome in elderly patients with major
      depressive disorder: follow up study.
AB  - OBJECTIVE: To determine the difference in outcome among elderly people with major
      depression who do and do not have severe white matter lesions on magnetic
      resonance imaging. DESIGN: Follow up study. SETTING: Two psychiatric and two
      general hospitals in Melbourne, Australia. SUBJECTS: 60 depressed subjects aged
      over 55 referred to hospital psychiatric services with major depressive disorder
      meeting American Psychiatric Association (DSM-IIIR) criteria. MAIN OUTCOME
      MEASURE: Proportion with good outcome as determined by full recovery from initial
      illness and no evidence of depressive relapse or cognitive decline during follow
      up among those with and without lesions. RESULTS: Mean (SD) follow up was 31.9
      (9.9) months. Survival analysis showed a significant effect of severe lesions on
      time to poor outcome (P=0.04), with median survival 136 days in those with severe
      lesions compared with 315 days in those without. CONCLUSION: Severe white matter
      change on magnetic resonance imaging is associated with poor outcome in elderly
      depressed subjects.

PMID- 9765167
TI  - Does initial management affect the rate of repetition of deliberate self harm?
      cohort study.

PMID- 9765168
TI  - Clouding of Surgeons' spectacles 

PMID- 9765170
TI  - The collins case 

PMID- 9765169
TI  - Comparison of potency of inhaled beclomethasone and budesonide in New Zealand:
      retrospective study of computerised general practice records.
AB  - OBJECTIVE: To determine whether inhaled budesonide and beclomethasone are
      equipotent in the treatment of asthma in primary care. DESIGN: Retrospective
      study of computerised clinical records from 28 general practices in New Zealand.
      SUBJECTS: 5930 patients who received 16 725 prescriptions for inhaled budesonide
      or beclomethasone from 1 July 1994 to 30 June 1995. SETTING: General practices on
      the database of the Royal New Zealand College of General Practitioners Research
      Unit. Linked information from secondary care was available for a subset of the
      practices. MAIN OUTCOME MEASURE: Mean prescribed daily inhaled corticosteroid
      dose. RESULTS: The daily prescribed dose was higher for patients receiving
      inhaled budesonide (mean 979 microg) than beclomethasone (mean 635 microg), a
      difference of 344 microg (95% confidence interval 313 to 376 microg). This
      difference was consistent in all age bands and with different types of inhalation
      device. Evidence of systematic prescribing of higher doses of budesonide to
      patients with more severe asthma was not found. CONCLUSIONS: In primary care in
      New Zealand evidence suggests that budesonide is less potent than beclomethasone.
      Consideration of validated, established, and other possible markers of asthma
      severity did not support confounding by severity as a reason for the higher
      prescribed doses of budesonide. Pending further epidemiological evaluation,
      international asthma guidelines may need to be modified on the equivalence of
      inhaled corticosteroid doses. Furthermore, the comparative potency of newly
      developed inhaled steroids in clinical trials will need to be confirmed in
      appropriately designed epidemiological studies based in general practice.

PMID- 9765172
TI  - The chair sign 

PMID- 9765173
TI  - Diving and oxygen.

PMID- 9765174
TI  - The second phase of priority setting 

PMID- 9765171
TI  - The muscular dystrophies.

PMID- 9765176
TI  - Academic dress 

PMID- 9765175
TI  - The importance of theories in health care.

PMID- 9765177
TI  - The Swiss heroin trials. Trial is needed comparing decriminalisation of heroin
      with existing policy of prohibition.

PMID- 9765178
TI  - Recovered memories of childhood abuse. We must tell patients that they were not
      to blame.

PMID- 9765179
TI  - Mouth care and skin care in palliative medicine.

PMID- 9765180
TI  - Number needed to harm should be measured for treatments.

PMID- 9765181
TI  - Systematic review of trials comparing antibiotic with placebo for acute cough in
      adults. Data do not justify study's conclusions.

PMID- 9765182
TI  - Celebrity's death from cancer resulted in increased calls to CancerBACUP.

PMID- 9765183
TI  - Sumatriptan is not the only analgesic used inappropriately.

PMID- 9765184
TI  - Suicide in patients with stroke. Depression may be caused by symptoms affecting
      lower urinary tract.

PMID- 9765185
TI  - Early diagnosis of cystic fibrosis can improve children's growth.

PMID- 9765186
TI  - Smoking and risk of myocardial infarction. Statistical and biological
      interactions should not be confused.

PMID- 9765188
TI  - Junior doctors advised on self regulation 

PMID- 9765187
TI  - James alexander ("Hamish") chalmers 

PMID- 9765189
TI  - Retraction

PMID- 9765190
TI  - German medical editors' uphill struggle 

PMID- 9765191
TI  - Did MONICA really say that? 

PMID- 9765192
TI  - Healthcare rationing: no desistance, no completion 

PMID- 9765193
TI  - Multiple doses of anticholinergics are beneficial in severe, acute childhood
      asthma 

PMID- 9765194
TI  - Warm clothing and housing prevent excess winter mortality 

PMID- 9765195
TI  - White matter lesions predict outcome in late depression 

PMID- 9765196
TI  - People who decline psychiatric assessment are more likely to repeat self harm 

PMID- 9765197
TI  - Inhaled budesonide may be less potent than beclomethasone in primary care 

PMID- 9765198
TI  - Priority setting reaches its second phase 

PMID- 9765199
TI  - The complexity of p53 modulation: emerging patterns from divergent signals.

PMID- 9765200
TI  - Tumor surveillance via the ARF-p53 pathway.

PMID- 9765201
TI  - The HIV-1 Tat cellular coactivator Tat-SF1 is a general transcription elongation
      factor.
AB  - The human immunodeficiency virus type 1 (HIV-1) Tat protein strongly and
      specifically stimulates transcription elongation from the HIV-1 LTR and provides
      an important in vitro model system to study this process. Here we use protein
      affinity chromatography to identify cellular factors involved in transcription
      elongation. A Tat-affinity column bound one transcription factor, Tat-SF1,
      efficiently and selectively. Tat-SF1 was identified originally as a Tat-specific
      coactivator, but we show it is a general transcription elongation factor. Our
      results also reveal the existence of an ATP-inactivatable general elongation
      factor (AIEF) required for Tat-SF1 activity and for which Tat can substitute
      functionally.

PMID- 9765202
TI  - Senescence of human fibroblasts induced by oncogenic Raf.
AB  - The oncogenes RAS and RAF came to view as agents of neoplastic transformation.
      However, in normal cells, these genes can have effects that run counter to
      oncogenic transformation, such as arrest of the cell division cycle, induction of
      cell differentiation, and apoptosis. Recent work has demonstrated that RAS
      elicits proliferative arrest and senescence in normal mouse and human
      fibroblasts. Because the Raf/MEK/MAP kinase signaling cascade is a key effector
      of signaling from Ras proteins, we examined the ability of conditionally active
      forms of Raf-1 to elicit cell cycle arrest and senescence in human cells.
      Activation of Raf-1 in nonimmortalized human lung fibroblasts (IMR-90) led to the
      prompt and irreversible arrest of cellular proliferation and the premature onset
      of senescence. Concomitant with the onset of cell cycle arrest, we observed the
      induction of the cyclin-dependent kinase (CDK) inhibitors p21(Cip1) and
      p16(Ink4a). Ablation of p53 and p21(Cip1) expression by use of the E6 oncoprotein
      of HPV16 demonstrated that expression of these proteins was not required for Raf
      induced cell cycle arrest or senescence. Furthermore, cell cycle arrest and
      senescence were elicited in IMR-90 cells by the ectopic expression of p16(Ink4a)
      alone. Pharmacological inhibition of the Raf/MEK/MAP kinase cascade prevented Raf
      from inducing p16(Ink4a) and also prevented Raf-induced senescence. We conclude
      that the kinase cascade initiated by Raf can regulate the expression of
      p16(Ink4a) and the proliferative arrest and senescence that follows. Induction of
      senescence may provide a defense against neoplastic transformation when the MAP
      kinase signaling cascade is inappropriately active.

PMID- 9765203
TI  - Premature senescence involving p53 and p16 is activated in response to
      constitutive MEK/MAPK mitogenic signaling.
AB  - Oncogenic Ras transforms immortal rodent cells to a tumorigenic state, in part,
      by constitutively transmitting mitogenic signals through the mitogen-activated
      protein kinase (MAPK) cascade. In primary cells, Ras is initially mitogenic but
      eventually induces premature senescence involving the p53 and p16(INK4a) tumor
      suppressors. Constitutive activation of MEK (a component of the MAPK cascade)
      induces both p53 and p16, and is required for Ras-induced senescence of normal
      human fibroblasts. Furthermore, activated MEK permanently arrests primary murine
      fibroblasts but forces uncontrolled mitogenesis and transformation in cells
      lacking either p53 or INK4a. The precisely opposite response of normal and
      immortalized cells to constitutive activation of the MAPK cascade implies that
      premature senescence acts as a fail-safe mechanism to limit the transforming
      potential of excessive Ras mitogenic signaling. Consequently, constitutive MAPK
      signaling activates p53 and p16 as tumor suppressors.

PMID- 9765204
TI  - Chromatin, TAFs, and a novel multiprotein coactivator are required for
      synergistic activation by Sp1 and SREBP-1a in vitro.
AB  - The promoter selectivity factor Sp1 often cooperates with other enhancer-binding
      proteins to activate transcription. To study the molecular underpinnings of these
      regulatory events, we have reconstituted in vitro the synergy observed in vivo
      between Sp1 and the sterol-regulated factor SREBP-1a at the low density
      lipoprotein receptor (LDLR) promoter. Using a highly purified human transcription
      system, we found that chromatin, TAFs, and a novel SREBP-binding coactivator
      activity, which includes CBP, are all required to mediate full synergistic
      activation by Sp1 and SREBP-1a. The SREBP-binding domain of CBP inhibits
      activation by SREBP-1a and Sp1 in a dominant-negative fashion that is both
      chromatin- and activator-specific. Whereas recombinant CBP alone is not
      sufficient to mediate activation, a human cellular fraction containing CBP can
      support high levels of chromatin-dependent synergistic activation. Purification
      of this activity to near homogeneity resulted in the identification of a
      multiprotein coactivator, including CBP, that selectively binds to the SREBP-1a
      activation domain and is capable of mediating high levels of synergistic
      activation by SREBP/Sp1 on chromatin templates. The development of a
      reconstituted chromatin transcription system has allowed us to isolate a novel
      coactivator that is recruited by the SREBP-1a activation domain and that
      functions in concert with TFIID to coordinate the action of multiple activators
      at complex promoters in the context of chromatin.

PMID- 9765205
TI  - Negative control of replication initiation by a novel chromosomal locus
      exhibiting exceptional affinity for Escherichia coli DnaA protein.
AB  - Replication of the Escherichia coli chromosome is initiated at a unique site,
      oriC. Concurrent initiation occurs at all oriC sites present in a cell once, and
      only once, per cell cycle. A mechanism to ensure cyclic initiation events was
      found operating through the chromosomal site, datA, a 1-kb segment located at
      94.7 min on the genetic map that titrates exceptionally large amounts of the
      bacterial initiator protein, DnaA. A strain lacking datA grew normally but
      exhibited an asynchronous initiation phenotype as a result of extra initiation
      events. This mutant phenotype was suppressed by DnaA-titrating plasmids.
      Furthermore, mutations in a 9-bp DnaA-binding sequence (the DnaA box) in datA
      were enough to induce the mutant phenotype. Thus, datA is a novel chromosomal
      element that appears to adjust a balance between free and bound DnaA for a single
      initiation event at a fixed time in the bacterial cell cycle. Titration of DnaA
      to newly duplicated datA during oriC sequestration, which is mediated by
      hemimethylated GATC sequences in oriC and the SeqA protein, would contribute to
      prevention of reinitiations when oriC is desequestered.

PMID- 9765206
TI  - Yeast telomeres exert a position effect on recombination between internal tracts
      of yeast telomeric DNA.
AB  - In Saccharomyces cerevisiae, proximity to a telomere affects both transcription
      and replication of adjacent DNA. In this study, we show that telomeres also
      impose a position effect on mitotic recombination. The rate of recombination
      between directly repeated tracts of telomeric C1-3A/TG1-3 DNA was reduced
      severely by proximity to a telomere. In contrast, recombination of two control
      substrates was not affected by telomere proximity. Thus, unlike position effects
      on transcription or replication, inhibition of recombination was sequence
      specific. Moreover, the repression of recombination was not under the same
      control as transcriptional repression (telomere position effect; TPE), as
      mutations in genes essential for TPE did not alleviate telomeric repression of
      recombination. The reduction in recombination between C1-3A/TG1-3 tracts near the
      telomere was caused by an absence of Rad52p-dependent events as well as a
      reduction in Rad1p-dependent events. The sequence-specific repression of
      recombination near the telomere was eliminated in cells that overexpressed the
      telomere-binding protein Rap1p, a condition that also increased recombination
      between C1-3A/TG1-3 tracts at internal positions on the chromosome. We propose
      that the specific inhibition between C1-3A/TG1-3 tracts near the telomere occurs
      through the action of a telomere-specific end-binding protein that binds to the
      single-strand TG1-3 tail generated during the processing of recombination
      intermediates. The recombination inhibitor protein may also block recombination
      between endogenous telomeres.

PMID- 9765207
TI  - Pleiotropic control of glucose and hormone responses by PRL1, a nuclear WD
      protein, in Arabidopsis.
AB  - The prl1 mutation localized by T-DNA tagging on Arabidopsis chromosome 4-44
      confers hypersensitivity to glucose and sucrose. The prl1 mutation results in
      transcriptional derepression of glucose responsive genes defining a novel
      suppressor function in glucose signaling. The prl1 mutation also augments the
      sensitivity of plants to growth hormones including cytokinin, ethylene, abscisic
      acid, and auxin; stimulates the accumulation of sugars and starch in leaves; and
      inhibits root elongation. PRL1 encodes a regulatory WD protein that interacts
      with ATHKAP2, an alpha-importin nuclear import receptor, and is imported into the
      nucleus in Arabidopsis. Potential functional conservation of PRL1 homologs found
      in other eukaryotes is indicated by nuclear localization of PRL1 in monkey COS-1
      cells and selective interaction of PRL1 with a nuclear protein kinase C-betaII
      isoenzyme involved in human insulin signaling.

PMID- 9765208
TI  - Synapse-specific and neuregulin-induced transcription require an ets site that
      binds GABPalpha/GABPbeta.
AB  - Localization of acetylcholine receptors (AChRs) to neuromuscular synapses is
      mediated by multiple pathways. Agrin, which is the signal for one pathway,
      stimulates a redistribution of previously unlocalized AChRs to synaptic sites.
      The signal for a second pathway is not known, but this signal stimulates
      selective transcription of AChR genes in myofiber nuclei located near the
      synaptic site. Neuregulin (NRG) is a good candidate for the extracellular signal
      that induces synapse-specific gene expression, since NRG is concentrated at
      synaptic sites and activates AChR gene expression in cultured muscle cells.
      Previous studies have demonstrated that 181 bp of 5' flanking DNA from the AChR
      delta-subunit gene are sufficient to confer synapse-specific transcription in
      transgenic mice and NRG responsiveness in cultured muscle cells, but the critical
      sequences within this cis-acting regulatory region have not been identified. We
      transfected AChR delta-subunit-hGH gene fusions into a muscle cell line, and we
      show that a potential binding site for Ets proteins is required for NRG-induced
      gene expression. Furthermore, we produced transgenic mice carrying AChR delta
      subunit-hGH gene fusions with a mutation in this NRG-response element (NRE), and
      we show that this NRE is necessary for synapse-specific transcription in mice.
      The NRE binds proteins in myotube nuclear extracts, and nucleotides that are
      important for NRG responsiveness are likewise critical for formation of the
      protein-DNA complex. This complex contains GABPalpha, an Ets protein, and
      GABPbeta, a protein that lacks an Ets domain but dimerizes with GABPalpha,
      because formation of the protein-DNA complex is inhibited by antibodies to either
      GABPalpha or GABPbeta. These results demonstrate that synapse-specific and NRG
      induced gene expression require an Ets-binding site and suggest that
      GABPalpha/GABPbeta mediates the transcriptional response of the AChR delta
      subunit gene to synaptic signals, including NRG.

PMID- 9765209
TI  - Synergistic cooperation of TFE3 and smad proteins in TGF-beta-induced
      transcription of the plasminogen activator inhibitor-1 gene.
AB  - Members of the TGF-beta superfamily influence a broad range of biological
      activities including stimulation of wound healing and inhibition of cell growth.
      TGF-beta signals through type I and II receptor serine/ threonine kinases and
      induces transcription of many genes including plasminogen activator inhibitor-1
      (PAI-1). To identify proteins that participate in TGF-beta-induced gene
      expression, we developed a novel retrovirus-mediated expression cloning strategy;
      and using this approach, we established that transcription factor microE3 (TFE3)
      is involved in TGF-beta-induced activation of the PAI-1 promoter. We showed that
      TFE3 binds to an E-box sequence in PE2, a 56-bp promoter fragment of the PAI-1
      promoter, and that mutation of this sequence abolishes both TFE3 binding as well
      as TGF-beta-dependent activation. TFE3 and Smad3 synergistically activate the PE2
      promoter and phosphorylated Smad3 and Smad4 bind to a sequence adjacent to the
      TFE3-binding site in this promoter. Binding of both TFE3 and the Smad proteins to
      their cognate sequences is indispensable for TGF-beta-inducible activation of the
      PE2 promoter. Hence, TFE3 is an important transcription factor in at least one
      TGF-beta-activated signal transduction pathway.

PMID- 9765210
TI  - Eph signaling is required for segmentation and differentiation of the somites.
AB  - Somitogenesis involves the segmentation of the paraxial mesoderm into units along
      the anteroposterior axis. Here we show a role for Eph and ephrin signaling in the
      patterning of presomitic mesoderm and formation of the somites. Ephrin-A-L1 and
      ephrin-B2 are expressed in an iterative manner in the developing somites and
      presomitic mesoderm, as is the Eph receptor EphA4. We have examined the role of
      these proteins by injection of RNA, encoding dominant negative forms of Eph
      receptors and ephrins. Interruption of Eph signaling leads to abnormal somite
      boundary formation and reduced or disturbed myoD expression in the myotome.
      Disruption of Eph family signaling delays the normal down-regulation of her1 and
      Delta D expression in the anterior presomitic mesoderm and disrupts myogenic
      differentiation. We suggest that Eph signaling has a key role in the translation
      of the patterning of presomitic mesoderm into somites.

PMID- 9765211
TI  - Interaction of a nascent RNA structure with RNA polymerase is required for
      hairpin-dependent transcriptional pausing but not for transcript release.
AB  - Nascent RNA structures may regulate RNA chain elongation either directly through
      interaction with RNA polymerase or indirectly by disrupting nascent RNA contacts
      with polymerase or DNA. To distinguish these mechanisms we tested whether the
      effects of the his leader pause RNA hairpin could be mimicked by pairing of
      antisense DNA or RNA oligonucleotides to the nascent transcript. The his pause
      hairpin inhibits nucleotide addition when it forms 11 nucleotides from the
      transcript 3' end. It also can terminate transcription when base changes extend
      its stem to </=8 nucleotides from the 3' end. All oligonucleotides that disrupted
      the pause hairpin reduced the dwell time of RNA polymerase at the pause site
      dramatically, even when they mimicked the 11-nucleotide 3'-proximal RNA spacing
      or created a suitably positioned RNA loop. Oligonucleotides that paired </=8
      nucleotides from the pause RNA 3' end could trigger transcript release, but only
      when added to an already paused complex. These results argue that direct
      interaction of a nascent RNA hairpin with RNA polymerase delays escape from a
      pause, but that indirect effects of a hairpin may trigger transcript release from
      a paused complex. Resistance of the paused complex to pyrophosphorolysis and its
      reversal by antisense oligonucleotides further suggest that interaction of the
      pause hairpin with RNA polymerase disengages the RNA 3' end from the active site.

PMID- 9765214
TI  - Electrostatic origin of the catalytic power of enzymes and the role of
      preorganized active sites.

PMID- 9765212
TI  - The flagellar anti-sigma factor FlgM actively dissociates Salmonella typhimurium
      sigma28 RNA polymerase holoenzyme.
AB  - The anti-sigma factor FlgM of Salmonella typhimurium inhibits transcription of
      class 3 flagellar genes through a direct interaction with the flagellar-specific
      sigma factor, sigma28. FlgM is believed to prevent RNA polymerase (RNAP)
      holoenzyme formation by sequestering free sigma28. We have analyzed FlgM-mediated
      inhibition of sigma28 activity in vitro. FlgM is able to inhibit sigma28 activity
      even when sigma28 is first allowed to associate with core RNAP. Surface plasmon
      resonance (SPR) was used to evaluate the interaction between FlgM and both
      sigma28 and sigma28 holoenzyme (Esigma28). The Kd of the sigma28-FlgM complex is
      approximately 2 x 10(-10) M; missense mutations in FlgM that cause a defect in
      sigma28 inhibition in vivo increase the Kd of this interaction by 4- to 10-fold.
      SPR measurements of Esigma28 dissociation in the presence of FlgM indicate that
      FlgM destabilizes Esigma28, presumably via an interaction with the sigma subunit.
      Our data provide the first direct evidence of an interaction between FlgM and
      Esigma28. We propose that this secondary activity of FlgM, which we term
      holoenzyme destabilization, enhances the sensitivity of the cell to changes in
      FlgM levels during flagellar biogenesis.

PMID- 9765215
TI  - Multitissue circadian expression of rat period homolog (rPer2) mRNA is governed
      by the mammalian circadian clock, the suprachiasmatic nucleus in the brain.
AB  - The period (per) gene, controlling circadian rhythms in Drosophila, is expressed
      throughout the body in a circadian manner. A homolog of Drosophila per was
      isolated from rat and designated as rPer2. The rPER2 protein showed 39 and 95%
      amino acid identity with mPER1 and mPER2 (mouse homologs of per) proteins,
      respectively. A robust circadian fluctuation of rPer2 mRNA expression was
      discovered not only in the suprachiasmatic nucleus (SCN) of the hypothalamus but
      also in other tissues including eye, brain, heart, lung, spleen, liver, and
      kidney. Furthermore, the peripheral circadian expression of rPer2 mRNA was
      abolished in SCN-lesioned rats that showed behavioral arrhythmicity. These
      findings suggest that the multitissue circadian expression of rPer2 mRNA was
      governed by the mammalian brain clock SCN and also suggest that the rPer2 gene
      was involved in the circadian rhythm of locomotor behavior in mammals.

PMID- 9765213
TI  - Identification of APN2, the Saccharomyces cerevisiae homolog of the major human
      AP endonuclease HAP1, and its role in the repair of abasic sites.
AB  - Abasic (AP) sites arise in DNA through spontaneous base loss and enzymatic
      removal of damaged bases. APN1 encodes the major AP-endonuclease of Saccharomyces
      cerevisiae. Human HAP1 (REF1) encodes the major AP endonuclease which, in
      addition to its role in DNA repair, functions as a redox regulatory protein. We
      identify APN2, the yeast homolog of HAP1 and provide evidence that Apn1 and Apn2
      represent alternate pathways for repairing AP sites. The apn1Delta apn2Delta
      strain displays a highly elevated level of MMS-induced mutagenesis, which is
      dependent on the REV3, REV7, and REV1 genes. Our findings indicate that AP sites
      are highly cytotoxic and mutagenic in eukaryotes, and that the REV3, REV7-encoded
      DNA polymerase zeta mediates the mutagenic bypass of AP sites.

PMID- 9765216
TI  - Biochemical and evolutionary significance of phospholipid methylation.
AB  - All nucleated mammalian cells synthesize phosphatidylcholine from choline via the
      CDP-choline pathway. Hepatocytes have a second pathway for the synthesis of
      phosphatidylcholine, a stepwise methylation of phosphatidylethanolamine,
      catalyzed by phosphatidylethanolamine N-methyltransferase and encoded by the
      Pempt gene. We report that when Pempt-deficient mice were fed a choline-deficient
      diet for 3 days, severe liver pathology occurred apparently due to a lack of
      phosphatidylcholine biosynthesis. The hepatic concentration of
      phosphatidylcholine decreased by 50% compared with wild type mice on the diet.
      The levels of plasma triacylglycerols and cholesterol were decreased by greater
      than 90% in the Pempt-deficient mice. We suggest that the Pempt gene has been
      maintained during evolution to provide phosphatidylcholine when dietary choline
      is insufficient, as might occur during starvation or pregnancy.

PMID- 9765217
TI  - Induction of Rb-associated protein (RbAp46) by Wilms' tumor suppressor WT1
      mediates growth inhibition.
AB  - The Wilms' tumor suppressor gene, wt1, encodes a zinc-finger transcription
      factor, WT1, that plays an important role in controlling urogenital development.
      Previously, WT1 has been shown to inhibit cell growth and to repress
      transcription initiated from the promoters of a number of growth-promoting genes.
      However, few physiological target genes that are transcriptionally activated by
      WT1 have been established. Using suppression subtractive hybridization polymerase
      chain reaction, we isolated a WT1 target gene that is up-regulated about 15-fold
      in cells expressing WT1. The gene was identified as retinoblastoma suppressor
      (Rb)-associated protein 46 (RbAp46), a nuclear protein that interacts physically
      with Rb and is a component of the human mSin3 co-repressor complex. Cells
      transfected with RbAp46 cDNA formed fewer colonies than the control cells, and
      RbAp46 suppressed the growth rate (by about 2-fold) of transfected cells. In the
      developing kidney and gonad, RbAp46 exhibits an expression pattern similar to
      that of WT1. We conclude that RbAp46 has strong growth inhibition activity and
      may function as an important mediator of WT1's function.

PMID- 9765218
TI  - A novel protein containing Cdc10/SWI6 motifs regulates expression of mRNA
      encoding catecholamine biosynthesizing enzymes.
AB  - Catecholaminergic (dopaminergic, noradrenergic, and adrenergic) transmitter
      phenotypes require the cooperative actions of four biosynthetic enzymes: tyrosine
      hydroxylase, aromatic L-amino acid decarboxylase, dopamine beta-hydroxylase, and
      phenylethanolamine N-methyltransferase. Mechanisms that control expression of
      these enzymes in a transmitter phenotype-specific manner, however, are poorly
      understood. Here, we provide evidence that overexpression of a novel cdc10/SWI6
      motif-containing protein, V-1, elicits the coordinate up-regulation of tyrosine
      hydroxylase, aromatic L-amino acid decarboxylase, and dopamine beta-hydroxylase
      mRNAs in the neuronal cell line PC12D, and as a result, catecholamine levels are
      increased. Furthermore, V-1 is strongly expressed in the cytoplasm of rat
      chromaffin cells of adrenal medulla. Thus, V-1 may act as a cytoplasmic
      protein/protein adapter and be involved in control of the catecholaminergic
      phenotype expression via an intracellular pathway signaling to the nucleus.

PMID- 9765219
TI  - A 17-amino acid insert changes UDP-N-acetylhexosamine pyrophosphorylase
      specificity from UDP-GalNAc to UDP-GlcNAc.
AB  - We previously reported the purification of a UDP-N-acetylhexosamine (UDP-HexNAc)
      pyrophosphorylase from pig liver that catalyzed the synthesis of both UDP-GlcNAc
      and UDP-GalNAc from UTP and the appropriate HexNAc-1-P (Szumilo, T., Zeng, Y.,
      Pastuszak, I., Drake, R., Szumilo, H., and Elbein, A. D. (1996) J. Biol. Chem.
      271, 13147-13154). Both sugar nucleotides were synthesized at nearly the same
      rate, although the Km for GalNAc-1-P was about 3 times higher than for GlcNAc-1
      P. Based on native gels and SDS-polyacrylamide gel electrophoresis, the enzyme
      appeared to be a dimer of 120 kDa composed of two subunits of about 57 and 64
      kDa. Three peptides sequenced from the 64-kDa protein and two from the 57-kDa
      protein showed 100% identity to AGX1, a 57-kDa protein of unknown function from
      human sperm. An isoform called AGX2 is identical in sequence to AGX1 except that
      it has a 17-amino acid insert near the carboxyl terminus. We expressed the AGX1
      and AGX2 genes in Escherichia coli. The protein isolated from the AGX1 clone
      comigrated on SDS gels with the liver 57-kDa pyrophosphorylase subunit and was 2
      3 times more active with GalNAc-1-P than with GlcNAc-1-P. On the other hand, the
      protein from the AGX2 clone migrated with the liver 64-kDa pyrophosphorylase
      subunit and had 8-fold better activity with GlcNAc-1-P than with GalNAc-1-P.
      These results indicate that insertion of the 17-amino acid peptide modifies the
      specificity of the pyrophosphorylase from synthesis of UDP-GalNAc to synthesis of
      UDP-GlcNAc.

PMID- 9765220
TI  - Hormone-induced translocation of thyroid hormone receptors in living cells
      visualized using a receptor green fluorescent protein chimera.
AB  - Thyroid hormone nuclear receptors (TRs) are ligand-dependent transcription
      factors that regulate growth, differentiation, and development. To understand the
      role of the hormone, 3,3', 5-triiodo-L-thyronine (T3), in the nuclear
      translocation and targeting of TRs to the regulatory sites in chromatin, we
      appended green fluorescent protein (GFP) to the human TR subtype beta1 (TRbeta1).
      The fusion of GFP to the amino terminus of TRbeta1 protein did not alter T3
      binding or transcriptional activities of the receptor. The subcellular
      localization of GFP-TRbeta1 in living cells was visualized by laser-scanning
      confocal microscopy. In the presence of T3, the expressed GFP-TRbeta1 was
      predominately localized in the nucleus, exhibiting a nuclear/cytoplasmic ratio of
      approximately 5.5. No GFP-TRbeta1 was detected in the nucleolus. In the absence
      of T3, more GFP-TRbeta1 was present in the cytoplasm, exhibiting a
      nuclear/cytoplasmic ratio of approximately 1.5. In these cells, cytoplasmic GFP
      TRbeta1 could be induced to enter the nucleus by T3. The T3-induced translocation
      was blocked when Lys184-Arg185 in domain D of TRbeta1 was mutated to Ala184
      Ala185. Furthermore, the inability of the mutant TR to translocate to the nucleus
      correlated with the loss of most of its transcriptional activity. These results
      suggest that TR functions may, in part, be regulated by T3-induced nuclear entry.

PMID- 9765221
TI  - Purification and properties of a novel chloroplast stromal peptidase. Processing
      of polyphenol oxidase and other imported precursors.
AB  - Polyphenol oxidases (PPOs) are nuclear-encoded chloroplast proteins that are
      targeted to the thylakoid lumen by a bipartite presequence. The N-terminal part
      of this sequence is removed by a stromal processing peptidase (SPP), and the
      resulting intermediate is translocated across the thylakoid and processed to the
      mature protein. A 4800-fold-purified SPP processed a PPO precursor (pPPO) at a
      site identical to that occurring in organelle. The in vitro product of SPP action
      on pPPO was further processed and translocated by thylakoids. This SPP processed
      other precursors but was inactive toward those of light-harvesting chlorophyll
      binding proteins. The enzyme appeared to be a metalloendopeptidase, like
      previously reported SPPs. However, it differed in substrate specificity, apparent
      size, and, most significantly, cleavage site of pPPO. Whereas the processing
      sites of lumen proteins determined so far were relatively distant from the
      hydrophobic core of the thylakoid targeting domain, pPPO was cleaved immediately
      before this domain. Cleavage removed the twin arginine motif characteristic of
      thylakoid targeting domains of lumen proteins, which are translocated by the
      DeltapH-dependent pathway. The possible significance of these observations to PPO
      translocation mechanism is discussed. It is suggested that several SPPs may exist
      in chloroplasts with preferences for different subsets of precursors.

PMID- 9765222
TI  - The phosphorylation of protein S6 modulates the interaction of the 40 S ribosomal
      subunit with the 5'-untranslated region of a dictyostelium pre-spore-specific
      mRNA and controls its stability.
AB  - AC914 mRNA, a pre-spore-specific mRNA that accumulates only in the post
      aggregation stage of development, is transcribed constitutively as shown by
      nuclear run-off experiments and by fusing its promoter to the luciferase reporter
      gene. The same mRNA disappears quickly from disaggregated cells. If the 5'
      untranslated region (5'UTR) of the constitutively expressed Actin 15 mRNA is
      substituted for the 5'UTR of AC914 mRNA, this can no longer be destabilized and
      accumulates both in growing and disaggregated cells. If the 5'UTR of AC914 mRNA
      is substituted for the 5'UTR of Actin 15 mRNA, the latter accumulates only in
      aggregated cells. Pactamycin, but not other inhibitors of protein synthesis,
      prevents AC914 mRNA from being destabilized in disaggregated cells, suggesting a
      role of 40 S subunits in the destabilization. This has been confirmed by using an
      in vitro system in which the in vivo stability of different mRNAs is reproduced.
      A protein kinase A-dependent phosphorylation of ribosomal protein S6 determines
      whether 40 S subunits are capable or not of destabilizing AC914 mRNA in the in
      vitro system.

PMID- 9765223
TI  - delta-Atracotoxins from australian funnel-web spiders compete with scorpion alpha
      toxin binding but differentially modulate alkaloid toxin activation of voltage
      gated sodium channels.
AB  - delta-Atracotoxins from the venom of Australian funnel-web spiders are a unique
      group of peptide toxins that slow sodium current inactivation in a manner similar
      to scorpion alpha-toxins. To analyze their interaction with known sodium channel
      neurotoxin receptor sites, we studied their effect on [3H]batrachotoxin and 125I
      Lqh II (where Lqh is alpha-toxin II from the venom of the scorpion Leiurus
      quinquestriatus hebraeus) binding and on alkaloid toxin-stimulated 22Na+ uptake
      in rat brain synaptosomes. delta-Atracotoxins significantly increased
      [3H]batrachotoxin binding yet decreased maximal batrachotoxin-activated 22Na+
      uptake by 70-80%, the latter in marked contrast to the effect of scorpion alpha
      toxins. Unlike the inhibition of batrachotoxin-activated 22Na+ uptake, delta
      atracotoxins increased veratridine-stimulated 22Na+ uptake by converting
      veratridine from a partial to a full agonist, analogous to scorpion alpha-toxins.
      Hence, delta-atracotoxins are able to differentiate between the open state of the
      sodium channel stabilized by batrachotoxin and veratridine and suggest a distinct
      sub-conductance state stabilized by delta-atracotoxins. Despite these actions,
      low concentrations of delta-atracotoxins completely inhibited the binding of the
      scorpion alpha-toxin, 125I-Lqh II, indicating that they bind to similar, or
      partially overlapping, receptor sites. The apparent uncoupling between the
      increase in binding but inhibition of the effect of batrachotoxin induced by
      delta-atracotoxins suggests that the binding and action of certain alkaloid
      toxins may represent at least two distinguishable steps. These results further
      contribute to the understanding of the complex dynamic interactions between
      neurotoxin receptor site areas related to sodium channel gating.

PMID- 9765224
TI  - Pro-caspase-3 is a major physiologic target of caspase-8.
AB  - The apoptotic signal triggered by ligation of members of the death receptor
      family is promoted by sequential activation of caspase zymogens. We show here
      that in a purified system, the initiator caspases-8 and -10 directly process the
      executioner pro-caspase-3 with activation rates (kcat/Km) of 8.7 x 10(5) and 2.8
      x 10(5) M-1 s-1, respectively. These rates are of sufficient magnitude to
      indicate direct processing in vivo. Differentially processed forms of caspase-3
      that accumulate during its activation have similar rates of activation,
      activities, and specificities. The pattern and rate of caspase-8 induced
      activation of pro-caspase-3 in cytosolic extracts was the same as in a purified
      system. Moreover, immunodepletion of a putative intermediary in the pathway to
      activation, pro-caspase-9, was without consequence. Taken together these data
      demonstrate that the initiator caspase-8 can directly activate pro-caspase-3
      without the requirement for an accelerator. The in vitro data thus help to
      deconvolute previous in vivo transfection studies which have debated the role of
      a direct versus indirect transmission of the apoptotic signal generated by
      ligation of death receptors.

PMID- 9765225
TI  - Transforming growth factor-beta stimulates the production of
      osteoprotegerin/osteoclastogenesis inhibitory factor by bone marrow stromal
      cells.
AB  - Osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF) is a recently
      identified cytokine that belongs to the tumor necrosis factor receptor
      superfamily and regulates bone mass by inhibiting osteoclastic bone resorption.
      The present study was undertaken to determine whether OPG/OCIF is produced in
      bone microenvironment and how the expression is regulated. A transcript for
      OPG/OCIF at 3.1 kilobases was detected in bone marrow stromal cells (ST2 and
      MC3T3-G2/PA6) as well as in osteoblastic cells (MC3T3-E1). Transforming growth
      factor-beta1 (TGF-beta1) markedly increased the steady-state level of OPG/OCIF
      mRNA in a dose-dependent manner, while TGF-beta1 suppressed the mRNA expression
      of tumor necrosis factor-related activation-induced cytokine (TRANCE)/receptor
      activator of NF-kappaB ligand (RANKL), a positive regulator of osteoclastogenesis
      to which OPG/OCIF binds. The effect of TGF-beta1 on the expression of OPG/OCIF
      mRNA was transient, with a peak level at 3-6 h. The up-regulation of OPG/OCIF
      mRNA by TGF-beta1 in ST2 cells did not require de novo protein synthesis and
      involved both a transcriptional and a post-transcriptional mechanism. Western
      blot analysis and an enzyme-linked immunosorbent assay revealed that TGF-beta1
      significantly increased the secretion of OPG/OCIF protein by ST2 cells at 6-24 h.
      In murine bone marrow cultures, TGF-beta1 markedly inhibited the formation of
      tartrate-resistant acid phosphatase-positive multinucleated osteoclast-like cells
      in the presence of 1,25-dihydroxyvitamin D3, whose effect was significantly
      reversed by a neutralizing antibody against OPG/OCIF. These results suggest that
      TGF-beta1 negatively regulates osteoclastogenesis, at least in part, through the
      induction of OPG/OCIF by bone marrow stromal cells and that the balance between
      OPG/OCIF and TRANCE/RANKL in local environment may be an important determinant of
      osteoclastic bone resorption.

PMID- 9765226
TI  - The hepatitis B virus X protein is a co-activator of activated transcription that
      modulates the transcription machinery and distal binding activators.
AB  - Hepatitis B virus X protein (HBx) transactivates viral and cellular genes through
      a wide variety of cis-elements, but the mechanism has not been well elucidated.
      Evidence for nuclear events in HBx transactivation has been reported. Here we
      examine the role of HBx in modulation of transcription with a transient
      transfection system and an in vitro transcription assay. Reporters bearing Gal4
      binding sites were applied to avoid the effects of endogenous transcription
      factors with or without signaling processes. The Gal4-DNA binding domain fused
      form of HBx exhibited no effect on Gal4-responsive reporters. However, HBx
      augmented activated transcription by transcriptional activators, suggesting HBx
      retains a co-activator but not a transcriptional activator function. The
      functional domain for co-activation was the same as that for HBx transactivation,
      and the transcription factor IIB- and RNA polymerase II subunit 5-interacting
      sites of HBx, which were critical for HBx transactivation, were shown to be
      crucial for the co-activation function. Importantly, HBx stimulated transcription
      on templates bearing the X responsive elements in vitro with endogenous
      activators. These results imply that HBx acts as a co-activator that modulates
      transcriptional machinery and distal-binding activators, which may explain one of
      the mechanisms of transactivation by HBx when localized in nuclei.

PMID- 9765227
TI  - EDG1 is a functional sphingosine-1-phosphate receptor that is linked via a Gi/o
      to multiple signaling pathways, including phospholipase C activation, Ca2+
      mobilization, Ras-mitogen-activated protein kinase activation, and adenylate
      cyclase inhibition.
AB  - In Chinese hamster ovary (CHO) cells transiently transfected with an expression
      vector for EDG1, but not an empty vector, sphingosine-1-phosphate (SP) at a
      concentration as low as 10(-10) M caused an increase in the intracellular free
      Ca2+ concentration ([Ca2+]i) as a result of mobilization of Ca2+ from both
      intracellular and extracellular pools. In a CHO clone stably expressing EDG1
      receptor (CHO-EDG1 cells), SP induced increases in the production of inositol
      phosphates and the [Ca2+]i and inhibited forskolin-induced increase in the
      cellular cAMP content, all in a manner sensitive to pertussis toxin. SP also
      activated mitogen-activated protein kinase in CHO-EDG1 cells in pertussis toxin
      sensitive and Ras-dependent manners. To evaluate the spectrum of agonists for
      EDG1, we used human erythroleukemia (HEL) cells, which at naive state do not
      respond to SP or structurally related lipids with an increase in the [Ca2+]i. In
      HEL cells stably expressing EDG1 receptor (HEL-EDG1 cells), SP dose-dependently
      increased the [Ca2+]i with half-maximal and maximal concentration values of 10(
      9) and 3 x 10(-7) M, respectively; sphingosylphosphorylcholine at exclusively
      high concentrations, but not sphingosine at all, also increased the [Ca2+]i. HEL
      EDG1 cells bound 32P-labeled SP, which was displaced dose dependently by
      unlabeled SP. These results indicate that EDG1, a member of the EDG family G
      protein-coupled receptors, is a specific, high-affinity SP receptor.

PMID- 9765228
TI  - Carbachol stimulates transactivation of epidermal growth factor receptor and
      mitogen-activated protein kinase in T84 cells. Implications for carbachol
      stimulated chloride secretion.
AB  - We have examined the role of tyrosine phosphorylation in regulation of calcium
      dependent chloride secretion across T84 colonic epithelial cells. The calcium
      mediated agonist carbachol (CCh, 100 microM) stimulated a time-dependent increase
      in tyrosine phosphorylation of a range of proteins (with molecular masses ranging
      up to 180 kDa) in T84 cells. The tyrosine kinase inhibitor, genistein (5 microM),
      significantly potentiated chloride secretory responses to CCh, indicating a role
      for CCh-stimulated tyrosine phosphorylation in negative regulation of CCh
      stimulated secretory responses. Further studies revealed that CCh stimulated an
      increase in both phosphorylation and activity of the extracellular signal
      regulated kinase (ERK) isoforms of mitogen-activated protein kinase. Chloride
      secretory responses to CCh were also potentiated by the mitogen-activated protein
      kinase inhibitor, PD98059 (20 microM). Phosphorylation of ERK in response to CCh
      was mimicked by the protein kinase C (PKC) activator, phorbol myristate acetate
      (100 nM), but was not altered by the PKC inhibitor GF 109203X (1 microM). ERK
      phosphorylation was also induced by epidermal growth factor (EGF) (100 ng/ml).
      Immunoprecipitation/Western blot studies revealed that CCh stimulated tyrosine
      phosphorylation of the EGF receptor (EGFr) and increased co-immunoprecipitation
      of the adapter proteins, Shc and Grb2, with the EGFr. An inhibitor of EGFr
      phosphorylation, tyrphostin AG1478 (1 microM), reversed CCh-stimulated
      phosphorylation of both EGFr and ERK. Tyrphostin AG1478 also potentiated chloride
      secretory responses to CCh. We conclude that CCh activates ERK in T84 cells via a
      mechanism involving transactivation of the EGFr, and that this pathway
      constitutes an inhibitory signaling pathway by which chloride secretory responses
      to CCh may be negatively regulated.

PMID- 9765229
TI  - Specific involvement of G proteins in regulation of serum response factor
      mediated gene transcription by different receptors.
AB  - Regulation of serum response factor (SRF)-mediated gene transcription by G
      protein subunits and G protein-coupled receptors was investigated in transfected
      NIH3T3 cells and in a cell line that was derived from mice lacking Galphaq and
      Galpha11. We found that the constitutively active forms of the alpha subunits of
      the Gq and G12 class of G proteins, including Galphaq, Galpha11, Galpha14,
      Galpha16, Galpha12, and Galpha13, can activate SRF in NIH3T3 cells. We also found
      that the type 1 muscarinic receptor (m1R) and alpha1-adrenergic receptor (AR)
      mediated SRF activation is exclusively dependent on Galphaq/11, while the
      receptors for thrombin, lysophosphatidic acid (LPA), thromboxane A2, and
      endothelin can activate SRF in the absence of Galphaq/11. Moreover, RGS12 but not
      RGS2, RGS4, or Axin was able to inhibit Galpha12 and Galpha13-mediated SRF
      activation. And RGS12, but not other RGS proteins, blocked thrombin- and LPA
      mediated SRF activation in the Galphaq/11-deficient cells. Therefore, the
      thrombin, LPA, thromboxane A2, and endothelin receptors may be able to couple to
      Galpha12/13. On the contrary, receptors including beta2- and alpha2-ARs, m2R, the
      dopamine receptors type 1 and 2, angiotensin receptors types 1 and 2, and
      interleukin-8 receptor could not activate SRF in the presence or absence of
      Galphaq/11, suggesting that these receptors cannot couple to endogenous G
      proteins of the G12 or Gq classes.

PMID- 9765230
TI  - A role for polysialic acid in neural cell adhesion molecule heterophilic binding
      to proteoglycans.
AB  - The neural cell adhesion molecule (NCAM) is known to participate in both
      homophilic and heterophilic binding, the latter including mechanisms that involve
      interaction with proteoglycans. The polysialic acid (PSA) moiety of NCAM can
      serve as a negative regulator of homophilic binding, but indirect evidence has
      suggested that PSA can also be involved in heterophilic binding. We have examined
      this potential positive role for PSA in terms of the adhesion of PSA-expressing
      mouse F11 cells and chick embryonic brain cells to substrates composed of the
      purified heparan sulfate proteoglycans agrin and 6C4. This adhesion was
      specifically inhibited by polyclonal anti-NCAM Fab antibodies, monoclonal anti
      PSA antibodies, PSA itself, and enzymatic removal of either PSA or heparan
      sulfate side chains. By contrast, the adhesion was not affected by
      chondroitinase, and cell binding to laminin was not inhibited by any of these
      treatments. A specific NCAM-heparan sulfate interaction in this adhesion was
      further indicated by its inhibition with monoclonal anti-NCAM Fab antibodies that
      recognize the known heparin-binding domain of NCAM and with the HBD-2 peptide
      derived from this region, but not with antibodies directed against other regions
      of the protein including the homophilic binding region. Together, the results
      suggest that PSA can act in vitro either as a receptor in NCAM heterophilic
      adhesion or as a promoter of binding between heparan sulfate proteoglycans and
      the NCAM heparin-binding domain.

PMID- 9765231
TI  - Hormone-evoked elementary Ca2+ signals are not stereotypic, but reflect
      activation of different size channel clusters and variable recruitment of
      channels within a cluster.
AB  - Previous studies of (InsP3)-evoked elementary Ca2+ events suggested a hierarchy
      of signals; fundamental events ("Ca2+ blips") arising from single InsP3 receptors
      (InsP3Rs), and intermediate events ("Ca2+ puffs") reflecting the coordinated
      opening of a cluster of InsP3Rs. The characteristics of such elementary Ca2+
      release signals provide insights into the functional interaction and distribution
      of InsP3Rs in living cells. Therefore we investigated whether elementary Ca2+
      signaling is truly represented by such stereotypic release events. A histogram of
      >900 events revealed a wide spread of signal amplitudes (20-600 nM; mean 216 +/-
      4 nM; n = 206 cells), which cannot be explained by stochastic variation of a
      stereotypic Ca2+ release site. We identified elementary Ca2+ release sites with
      consistent amplitudes (<20% difference) and locations with variable amplitudes
      (approximately 500% difference). Importantly, within single cells, distinct sites
      displayed events with significantly different mean amplitudes. Additional
      determinants affecting the magnitude of elementary Ca2+ release were identified
      to be (i) hormone concentration, (ii) day-to-day variability, and (iii) a
      progressively decreasing Ca2+ release during prolonged stimulation. We therefore
      suggest that elementary Ca2+ events are not stereotypic, instead a continuum of
      signals can be achieved by either recruitment of entire clusters with different
      numbers of InsP3Rs or by a graded recruitment of InsP3Rs within a cluster.

PMID- 9765233
TI  - RNA structure inhibits the TRAP (trp RNA-binding attenuation protein)-RNA
      interaction.
AB  - TRAP (trp RNA-binding attenuation protein) regulates expression of the tryptophan
      biosynthetic genes in response to tryptophan in Bacillus subtilis by binding to
      two sites containing a series of 9 or 11 (G/U)AG triplet repeats that are
      generally separated by two or three spacer nucleotides. Previous mutagenesis
      experiments have identified three TRAP residues, Lys-37, Lys-56, and Arg-58 that
      are essential for RNA binding. The location of these residues on the TRAP
      oligomer supports the proposal that RNA binds TRAP by encircling the TRAP
      oligomer. In this work, we show that RNAs containing 11 GAG or UAG repeats
      separated by CC dinucleotide spacers (((G/U)AGCC)11) form stable structures that
      inhibit binding to TRAP. This conclusion is based on the effects of temperature
      and Mg2+ on the affinity of TRAP for RNAs with CC spacers combined with UV
      hyperchromicity and circular dichroism. Furthermore, introducing the base
      analogue 7-deazaguanosine in the ((G/U)AGCC)11 RNAs stabilized the TRAP-RNA
      interaction. This effect was associated with decreased stability of the RNA
      structure as measured by circular dichroism spectroscopy. The precise nature of
      the structure of the ((G/U)AGCC)11 RNAs is not known but evidence is presented
      that it involves noncanonical interactions. We also observed that substitution of
      Arg-58 with Lys further reduced the ability of TRAP to interact with structured
      RNAs. Since in vivo function of TRAP may involve binding to structured RNAs, we
      suggest a potential function for this residue, which is conserved in TRAP from
      three different bacilli.

PMID- 9765232
TI  - ORC5L, a new member of the human origin recognition complex, is deleted in
      uterine leiomyomas and malignant myeloid diseases.
AB  - A new member of the human origin recognition complex (ORC) was cloned and
      identified as ORC5L. HsORC5p is a 50-kDa protein whose sequence is 38% identical
      and 62% similar to ORC5p from Drosophila melanogaster. Two alleles of ORC5L were
      identified, one with and one without an evolutionarily conserved purine
      nucleotide binding motif. HsORC5p is precipitated from cell extracts with HsORC2p
      and HsORC4p, indicating that it is part of the putative human ORC. The bulk of
      HsORC5p is in an insoluble nuclear fraction, whereas the other known human ORC
      subunits (HsORC1p, HsORC2p, and HsORC4p) are easily extracted in the nuclear
      soluble fractions and in S100 (HsORC1p). In addition, we identified an
      alternatively spliced mRNA from the same locus (HsORC5T). HsORC5Tp also formed a
      complex with HsORC4p but not with HsORC2p, suggesting it may play a regulatory
      role in the assembly of different ORC subcomplexes. HsORC5, HsORC5T, and HsORC4
      transcripts are abundant in spleen, ovary, and prostate in addition to tissues
      with high levels of DNA replication like testes and colon mucosa, implicating the
      human ORC proteins in functions besides DNA replication. Finally, the gene for
      ORC5L is located at chromosome 7, band q22, in the minimal region deleted in 10%
      of uterine leiomyomas and in 10-20% of acute myeloid leukemias and
      myelodysplastic syndromes.

PMID- 9765234
TI  - Newly discovered archaebacterial flap endonucleases show a structure-specific
      mechanism for DNA substrate binding and catalysis resembling human flap
      endonuclease-1.
AB  - Mammalian flap endonuclease-1 (FEN-1) is a structure-specific metalloenzyme that
      acts in processing of both the Okazaki fragments during lagging strand DNA
      synthesis and flap intermediates during DNA damage repair. We identified and
      cloned three open reading frames encoding a flap endonuclease from Archaeglobus
      fulgidus, Methanococcus jannaschii, and Pyrococcus furiosus, respectively. The
      deduced FEN-1 protein sequences share approximately 75% similarity with the human
      FEN-1 nuclease in the conserved nuclease domains, and extensive biochemical
      experiments indicate that the substrate specificities and catalytic activities of
      these enzymes have overall similarities with those of the human enzyme. Thus, FEN
      1 enzymes and likely reaction mechanisms are conserved across the eukaryotic and
      archaeal kingdoms. Detailed comparative analysis, however, reveals subtle
      differences among these four enzymes including distinctive substrate specificity,
      tolerance of the archaebacterial enzymes for acidic pHs and elevated
      temperatures, and variations in the metal-ion dependence of substrate cleavage.
      Although the archaebacterial enzymes were inactive at temperatures below 30
      degreesC, DNA binding occurred at temperatures as low as 4 degreesC and with or
      without metal ions. Thus, these archaeal enzymes may provide a means to dissect
      the specific binding and catalytic mechanisms of the entire FEN-1 family of
      structure-specific nucleases.

PMID- 9765235
TI  - Compartmentation of lactate and glucose metabolism in C6 glioma cells. A 13c and
      1H NMR study.
AB  - 13C and 1H NMR spectroscopy was used to investigate the metabolism of L-lactate
      and D-glucose in C6 glioma cells. The changing of lactate and glucose
      concentration in the extracellular medium of C6 glioma cells incubated with 5.5
      mM glucose and 11 mM lactate indicated a net production of lactate as the
      consequence of an active aerobic glycolysis. The 13C enrichments of various
      metabolites were determined after 4-h cell incubation in media containing both
      substrates, each of them being alternatively labeled in the form of either [3
      13C]L-lactate or [1-13C]D-glucose. Using 11 mM [3-13C]L-lactate, the enrichment
      of glutamate C4, 69%, was found higher than that of alanine C3, 32%, when that of
      acetyl-CoA C2 was 78%. These results indicated that exogenous lactate was the
      major substrate for the oxidative metabolism of the cells. Nevertheless, an
      active glycolysis occurred, leading to a net lactate production. This lactate
      was, however, metabolically different from the exogenous lactate as both lactate
      species did not mix into a unique compartment. The results were actually
      consistent with the concept of the existence of two pools of both lactate and
      pyruvate, wherein one pool was closely connected with exogenous lactate and was
      the main fuel for the oxidative metabolism, and the other pool was closely
      related to aerobic glycolysis.

PMID- 9765236
TI  - Purinergic receptor modulation of lipopolysaccharide signaling and inducible
      nitric-oxide synthase expression in RAW 264.7 macrophages.
AB  - Previous studies have suggested that the P2Z/P2X7 purinergic receptor can
      participate in nucleotide-induced modulation of lipopolysaccharide (LPS)
      stimulated inflammatory mediator production. To test this hypothesis, we
      evaluated whether antagonism of the P2Z/P2X7 receptor can influence LPS signaling
      and expression of the inducible form of nitric-oxide synthase (iNOS) in RAW 264.7
      macrophages. In the present study, we demonstrate that pretreatment of RAW 264.7
      macrophages with a P2Z/P2X7 receptor antagonist, periodate oxidized adenosine 5'
      triphosphate (o-ATP), substantially inhibits LPS-stimulated NO production and
      iNOS expression without altering cell viability. This effect on LPS-induced iNOS
      expression is mimicked by a pyridoxal-phosphate-based antagonist (pyridoxal
      phosphate-6-azophenyl-2',4'-disulfonic acid) of the P2Z/P2X7 purinergic receptor,
      indicating that these results are not unique to o-ATP. Additionally, o-ATP
      prevents cell death induced by P2Z/P2X7 receptor agonists. To ascertain how
      P2Z/P2X7 receptor antagonists influence LPS signaling, we evaluated the capacity
      of o-ATP to regulate LPS-mediated activation of the transcription factor, nuclear
      factor-kappaB, and the mitogen-activated protein kinases, extracellular signal
      regulated kinase (ERK) 1 and ERK2. These experiments reveal that pretreatment of
      RAW 264.7 cells with o-ATP attenuates the LPS stimulation of a nuclear factor
      kappaB-like binding activity. Moreover, the activation of ERK1 and ERK2 by LPS,
      but not by the phorbol ester, phorbol 12-myristate 13-acetate, is also blocked in
      RAW 264.7 cells by o-ATP pretreatment. In summary, these data suggest that the
      P2Z/P2X7 receptor modulates LPS-induced macrophage activation as assessed by iNOS
      expression and NO production. This report implicates the P2Z/P2X7 receptor in the
      control of protein kinase cascades and transcriptional processes, and these
      observations are likely to be important for the development of selective
      purinergic receptor antagonists for the treatment of septic shock.

PMID- 9765237
TI  - A study of the mechanism of inhibition of fibrinolysis by activated thrombin
      activable fibrinolysis inhibitor.
AB  - TAFI (thrombin-activable fibrinolysis inhibitor) is a recently described plasma
      zymogen that, when exposed to the thrombin-thrombomodulin complex, is converted
      by proteolysis at Arg92 to a basic carboxypeptidase that inhibits fibrinolysis
      (TAFIa). The studies described here were undertaken to elucidate the molecular
      basis for the inhibition of fibrinolysis. When TAFIa is included in a clot
      undergoing fibrinolysis induced by tissue plasminogen activator and plasminogen,
      the time to achieve lysis is prolonged, and free arginine and lysine are released
      over time. In addition, TAFIa prevents a 2.5-fold increase in the rate constant
      for plasminogen activation which occurs when fibrin is modified by plasmin in the
      early course of fibrin degradation. The effect is specific for the Glu- form of
      plasminogen. TAFIa prevents or at least attenuates positive feedback expressed
      through Lys-plasminogen formation during the process of fibrinolysis initiated by
      tissue plasminogen activator and plasminogen. TAFIa also inhibits plasmin
      activity in a clot and prolongs fibrinolysis initiated with plasmin. We conclude
      that TAFIa suppresses fibrinolysis by removing COOH-terminal lysine and arginine
      residues from fibrin, thereby reducing its cofactor functions in both plasminogen
      activation and the positive feedback conversion of Glu-plasminogen to Lys
      plasminogen. At relatively elevated concentrations, it also directly inhibits
      plasmin.

PMID- 9765238
TI  - Structure-function study of a heptad repeat positioned near the transmembrane
      domain of Sendai virus fusion protein which blocks virus-cell fusion.
AB  - A synthetic heptad repeat, SV-473, derived from Sendai virus fusion protein is a
      potent inhibitor of virus-cell fusion. In order to understand the mechanism of
      the inhibitory effect, we synthesized and fluorescently labeled SV-465, an
      extended version of SV-473 by one more heptad, its mutant peptide A17,24-SV-465,
      in which two heptadic leucines were substituted with two alanines, and its
      enatiomer D-SV-465, composed entirely of Damino acids. Similar mutations in the
      homologous fusion protein of the Newcastle disease virus drastically reduced its
      activity. The data revealed that SV-465, but not A17,24-SV-465 or its enantiomer,
      is highly active in inhibiting Sendai virus-induced hemolysis of red blood cells.
      None of the peptides interfere with the binding of virions to the target red
      blood cells as demonstrated by hemagglutinin assay. Fluorescence and circular
      dichroism (CD) spectroscopy indicated that: (i) only SV-465 could self-assemble
      in aqueous environment; (ii) only SV-465 could co-assemble with two other
      biologically active heptad repeats derived from Sendai virus fusion protein;
      (iii) SV-465 has a higher helical content than A17,24-SV-465 in solution, and
      (iv) all the peptides bind strongly to zwitterionic and negatively charged
      phospholipids. Polarized attenuated total reflection infrared spectroscopy
      revealed that they bound as monomers onto the surface of zwitterionic membranes
      with predominantly alpha-helical structures. The functional role of the amino
      acid 465-497 domain in Sendai virus-mediated membrane fusion is discussed in
      light of these findings.

PMID- 9765239
TI  - The influence of apolipoproteins on the hepatic lipase-mediated hydrolysis of
      high density lipoprotein phospholipid and triacylglycerol.
AB  - This study describes the influence of apolipoproteins on the hepatic lipase (HL)
      mediated hydrolysis of phospholipids and triacylglycerol in high density
      lipoproteins (HDL). HL-mediated hydrolysis was assessed in well characterized,
      homogeneous preparations of spherical reconstituted high density lipoproteins
      (rHDL). The rHDL were comparable in size and lipid composition and contained
      either apoA-I ((A-I)rHDL) or apoA-II ((A-II)rHDL) as their sole apolipoprotein
      constituent. Preparations of rHDL containing only cholesteryl esters (CE) in
      their core, (A-I/CE)rHDL and (A-II/CE)rHDL, were used to assess phospholipid
      hydrolysis. Preparations of rHDL that contained triacylglycerol as their
      predominant core lipid, (A-I/TG)rHDL and (A-II/TG)rHDL, were used to assess both
      triacylglycerol and phospholipid hydrolysis. The rHDL contained trace amounts of
      either radiolabeled phospholipid or radiolabeled triacylglycerol. Hydrolysis was
      measured as the release of radiolabeled nonesterified fatty acids (NEFA) from the
      rHDL. Kinetic analysis showed that HL had a greater affinity for the
      phospholipids in (A-II/CE)rHDL (Km(app) = 0.2 mM) than in (A-I/CE)rHDL (Km(app) =
      3.1 mM). This was also evident when hydrolysis was measured directly by
      quantitating NEFA mass. HL also had a greater affinity for the phospholipids and
      triacylglycerol in (A-II/TG)rHDL than in (A-I/TG)rHDL. The Vmax for phospholipid
      hydrolysis was, by contrast, greater for (A-I/CE)rHDL than for (A-II/CE)rHDL:
      309.3 versus 49.1 nmol of NEFA formed/ml of HL/h. Comparable Vmax values were
      obtained for the hydrolysis of the phospholipids in (A-II/TG)rHDL and (A
      I/TG)rHDL. In the case of triacylglycerol hydrolysis, the respective Vmax values
      for (A-I/TG)rHDL and (A-II/TG)rHDL were 1154.8 and 240.2 nmol of NEFA formed/ml
      of HL/h. These results show that apolipoproteins have a major influence on the
      kinetics of HL-mediated phospholipid and triacylglycerol hydrolysis in rHDL.

PMID- 9765240
TI  - Identification of free deaminated sialic acid (2-keto-3-deoxy-D-glycero-D-galacto
      nononic acid) in human red blood cells and its elevated expression in fetal cord
      red blood cells and ovarian cancer cells.
AB  - Chemical studies have shown the occurrence of the deaminated sialic acid 2-keto-3
      deoxy-D-glycero-D-galacto-nononic acid (KDN) in paired samples of blood obtained
      from mothers and newborns of healthy human individuals. Most of the KDN was found
      in red blood cells, although low levels were detected in mononuclear cells. No N
      glycolylneuraminic acid was detected. Unexpectedly, nearly all of the KDN in
      fetal cord and matched maternal red blood cells was present as the free sugar and
      comparatively little occurred conjugated or as cytidine 5'-KDN phosphate. The
      amount of free KDN in fetal newborn red blood cells was 2.4-fold higher than in
      red blood cells from the mothers or from healthy nonpregnant women. Free KDN was
      also identified in normal human ovaries, in ovarian tumors, and in ascites cells
      obtained from ovarian cancer patients. Importantly, as in fetal cord red blood
      cells, a distinguishing feature of KDN expression in ovarian tumor cells was an
      elevated level of free KDN compared with normal controls. A positive correlation
      was found between an increase in the ratio of free KDN/N-acetylneuraminic acid in
      ovarian adenocarcinomas and the stage of malignancy. This was particularly
      evident in tumor cells isolated from the ascites fluid. The central importance of
      these new findings is 2-fold. First, they show that free KDN is a minor but
      ubiquitous sialic acid in human red blood cells and that its elevated expression
      in red blood cells from fetal cord blood compared with maternal red blood cells
      may be developmentally related to blood cell formation during embryogenesis.
      Second, the enhanced expression of KDN in ovarian cancer cells suggests that this
      sialic acid, like the alpha2,8-linked polysialic acid glycotope, may be an
      oncofetal antigen in these tumors and thus could be an "early warning" signal for
      onset of disease and/or a marker for detection of recurrence of disease. These
      new findings highlight the importance of elucidating the role that KDN and KDN
      containing glycoconjugates may play in normal development and malignancy.

PMID- 9765241
TI  - Molecular mechanism of diltiazem interaction with L-type Ca2+ channels.
AB  - Benzothiazepine Ca2+ antagonists (such as (+)-cis-diltiazem) interact with
      transmembrane segments IIIS6 and IVS6 in the alpha1 subunit of L-type Ca2+
      channels. We investigated the contribution of individual IIIS6 amino acid
      residues for diltiazem sensitivity by employing alanine scanning mutagenesis in a
      benzothiazepine-sensitive alpha1 subunit chimera (ALDIL) expressed in Xenopus
      laevis oocytes. The most dramatic decrease of block by 100 microM diltiazem
      (ALDIL 45 +/- 4.8% inhibition) during trains of 100-ms pulses (0.1 Hz, -80 mV
      holding potential) was found after mutation of adjacent IIIS6 residues Phe1164(21
      +/- 3%) and Val1165 (8.5 +/- 1.4%). Diltiazem delayed current recovery by
      promoting a slowly recovering current component. This effect was similar in ALDIL
      and F1164A but largely prevented in V1165A. Both mutations slowed inactivation
      kinetics during a pulse. The reduced diltiazem block can therefore be explained
      by slowing of inactivation kinetics (F1164A and V1165A) and accelerated recovery
      from drug block (V1165A). The bulkier diltiazem derivative benziazem still
      efficiently blocked V1165A. From these functional and from additional radioligand
      binding studies with the dihydropyridine (+)-[3H]isradipine we propose a model in
      which Val1165 controls dissociation of the bound diltiazem molecule, and where
      bulky substituents on the basic nitrogen of diltiazem protrude toward the
      adjacent dihydropyridine binding domain.

PMID- 9765242
TI  - A new type of cytokine receptor antagonist directly targeting gp130.
AB  - The interleukin-6-type family of cytokines bind to receptor complexes that share
      gp130 as a common signal-transducing subunit. So far, receptor antagonists for
      interleukin-6-type cytokines have been constructed that still bind to the
      specific ligand binding subunit of the receptor complex, but have lost the
      ability to stimulate gp130. Such receptor antagonists compete for a specific
      receptor of a member of the cytokine family. Interleukin-6 only binds to gp130
      when complexed with the interleukin-6 receptor that exists as a membrane bound
      and soluble molecule. Here we have constructed fusion proteins that consist of
      the soluble form of the human interleukin-6 receptor covalently linked to
      interleukin-6 receptor antagonists. These fusion proteins directly bind to gp130.
      Moreover, at concentrations of 10-50 nM they completely neutralize not only the
      biological activity of interleukin-6 but also of other cytokines of the
      interleukin-6-type family that act via gp130 homodimers or gp130/LIF-R
      heterodimers. Therefore, these gp130 targeting cytokine antagonists might be
      useful therapeutic tools in disease states that are related to cytokines of the
      interleukin-6 family.

PMID- 9765243
TI  - Human procarboxypeptidase U, or thrombin-activable fibrinolysis inhibitor, is a
      substrate for transglutaminases. Evidence for transglutaminase-catalyzed cross
      linking to fibrin.
AB  - Procarboxypeptidase U (EC 3.4.17.20) (pro-CpU), also known as plasma
      procarboxypeptidase B and thrombin-activable fibrinolysis inhibitor, is a human
      plasma protein that has been implicated in the regulation of fibrinolysis. In
      this study, we show that pro-CpU serves as a substrate for transglutaminases.
      Both factor XIIIa and tissue transglutaminase catalyzed the polymerization of pro
      CpU and the cross-linking to fibrin as well as the incorporation of 5
      dimethylaminonaphthalene-1-sulfonyl cadaverine (dansylcadaverine),
      [14C]putrescine, and dansyl-PGGQQIV. These findings show that pro-CpU contains
      both amine acceptor (Gln) and amine donor (Lys) residues. The amine acceptor
      residues were identified as Gln2, Gln5, and Gln292, suggesting that both the
      activation peptide and the mature enzyme participate in the cross-linking
      reaction. These observations imply that transglutaminases may mediate covalent
      binding of pro-CpU to other proteins and cell surfaces in vivo. In particular,
      factor XIIIa may cross-link pro-CpU to fibrin during the latter part of the
      coagulation cascade, thereby helping protect the newly formed fibrin clot from
      premature plasmin degradation. Moreover, the cross-linking may facilitate the
      activation of pro-CpU, stabilize the enzymatic activity, and protect the active
      enzyme from further degradation.

PMID- 9765244
TI  - Proteasome-mediated degradation of apolipoprotein B targets both nascent peptides
      cotranslationally before translocation and full-length apolipoprotein B after
      translocation into the endoplasmic reticulum.
AB  - A major portion of newly synthesized apolipoprotein B (apoB) is degraded
      intracellularly. This degradation has been demonstrated to be mediated largely by
      the ubiquitin-proteasome pathway. We examined whether nascent apoB polypeptides
      or full-length apoB is selectively retrotranslocated from the endoplasmic
      reticulum into the cytosol for degradation. Herein, we found that full-length
      apoB as well as partial-length apoB peptides are ubiquitinated in HepG2 cells,
      and ubiquitination is an exclusively cytosolic process. Calnexin, which binds
      specifically to glycoproteins, has been postulated to promote apoB folding and
      complete translocation; we found that ubiquitinated apoB is bound to calnexin,
      suggesting that ubiquitinated apoB is glycosylated. In addition to calnexin
      binding, we have other pieces of evidence that the full-length intracellular
      ubiquitinated apoB is glycosylated, because (i) it binds to concanavalin A, and
      (ii) glycan can be demonstrated in the full-length ubiquitinated apoB by a
      chemical detection method involving oxidation of adjacent hydroxyl groups in the
      glycan moiety. Because glycosylation occurs inside the endoplasmic reticulum, the
      full-length glycosylated apoB must have been retrotranslocated into the cytosol
      for ubiquitination and proteasome-mediated degradation. Next we synchronized
      translation in HepG2 cells by puromycin treatment. A pulse-chase experiment using
      [35S]methionine labeling of intracellular apoB in these synchronized cells
      demonstrated that nascent partial-length apoB peptides are also ubiquitinated
      cotranslationally. We conclude that the ubiquitin proteasome-mediated degradation
      of apoB targets both nascent peptides cotranslationally before translocation as
      well as full-length apoB after its translocation into the endoplasmic reticulum.

PMID- 9765246
TI  - GroEL and GroES control of substrate flux in the in vivo folding pathway of phage
      P22 coat protein.
AB  - Our present understanding of the action of the chaperonins GroEL/S on protein
      folding is based primarily on in vitro studies, whereas the folding of proteins
      in the cellular milieu has not been as thoroughly investigated. We have developed
      a means of examining in vivo protein folding and assembly that utilizes the coat
      protein of bacteriophage P22, a naturally occurring substrate of GroEL/S. Here we
      show that amino acid substitutions in coat protein that cause a temperature
      sensitive-folding (tsf) phenotype slowed assembly rates upon increasing the
      temperature of cell growth. Raising cellular concentrations of GroEL/S increased
      the rate of assembly of the tsf mutant coat proteins to nearly that of wild-type
      (WT) coat protein by protecting a thermolabile folding intermediate from
      aggregation, thereby increasing the concentration of assembly-competent coat
      protein. The rate of release of the tsf coat proteins from the GroEL/S-coat
      protein ternary complex was approximately 2-fold slower at non-permissive
      temperatures when compared with the release of WT coat protein. However, the rate
      of release of WT or tsf coat proteins at each temperature remained constant
      regardless of GroEL/S levels. Thus, raising the cellular concentration of GroEL/S
      increased the amount of assembly-competent tsf coat proteins not by altering the
      rates of folding but by increasing the probability of GroEL/S-coat protein
      complex formation.

PMID- 9765245
TI  - A K+ channel splice variant common in human heart lacks a C-terminal domain
      required for expression of rapidly activating delayed rectifier current.
AB  - We have cloned HERG USO, a C-terminal splice variant of the human ether-a-go-go
      related gene (HERG), the gene encoding the rapid component of the delayed
      rectifier (IKr), from human heart, and we find that its mRNA is approximately 2
      fold more abundant than that for HERG1 (the originally described cDNA). After
      transfection of HERG USO in Ltk- cells, no current was observed. However,
      coexpression of HERG USO with HERG1 modified IKr by decreasing its amplitude,
      accelerating its activation, and shifting the voltage dependence of activation
      8.8 mV negative. As with HERG USO, HERGDeltaC (a HERG1 construct lacking the C
      terminal 462 amino acids) also produced no current in transfected cells. However,
      IKr was rescued by ligation of 104 amino acids from the C terminus of HERG1 to
      the C terminus of HERGDeltaC, indicating that the C terminus of HERG1 includes a
      domain (</=104 amino acids) that is critical for faithful recapitulation of IKr.
      The lack of this C-terminal domain not only explains the finding that HERG USO
      does not generate IKr but also indicates a similar mechanism for hitherto
      uncharacterized long QT syndrome HERG mutations that disrupt the splice site or
      the C-terminal. We suggest that the amplitude and gating of cardiac IKr depends
      on expression of both HERG1 and HERG USO.

PMID- 9765247
TI  - Induction of topoisomerase I cleavage complexes by the vinyl chloride adduct 1,N6
      ethenoadenine.
AB  - We used purified mammalian topoisomerases I (top1) and oligonucleotides to study
      top1-mediated cleavage and religation in the presence of a potent carcinogenic
      adduct, 1,N6-ethenoadenosine (epsilonA) incorporated immediately downstream of a
      unique top1 cleavage site. We found tha epsilonA markedly enhanced top1 cleavage
      complexes when it was incorporated at the +1 position of the top1 cleavage. This
      enhancement was due to a reduction of the religation step of the top1 reaction.
      In addition, epsilonA reduced the top1-mediated cleavage and decreased binding of
      the enzyme to DNA. We also studied the effects of the epsilonA adduct on top1
      trapping by camptothecin (CPT), a well known top1 inhibitor. CPT was inactive
      when epsilonA was present at the +1 position. Alkylation of the top1 cleavage
      complex by 7-chloromethyl-10,11-methylenedioxycamptothecin (7-ClMe-MDO-CPT) was
      also blocked by the epsilonA adduct. Altogether, these results demonstrate that
      the epsilonA carcinogenic adduct can efficiently trap human top1 and mimic CPT
      effects. Normal hydrogen bonding of the base pairs immediately downstream from
      the top1 cleavage site is probably essential for efficient DNA religation and
      binding of camptothecins in the top1 cleavage complex.

PMID- 9765248
TI  - Selective inhibition of HIV-1 reverse transcriptase by an antiviral inhibitor,
      (R)-9-(2-Phosphonylmethoxypropyl)adenine.
AB  - (R)-9-(2-Phosphonylmethoxypropyl)adenine (PMPA) is an acyclic nucleoside
      phosphonate that has been shown to be effective in the treatment of AIDS although
      it has a shorter separation between the adenine and phosphorus than dideoxy-AMP
      and dAMP. By using pre-steady state kinetic methods, we examined the
      incorporation of the diphosphate of PMPA, 2',3'-dideoxyadenosine 5'-triphosphate
      (ddATP), and dATP catalyzed by wild-type human immunodeficiency virus type 1 (HIV
      1) reverse transcriptase, an exonuclease-deficient T7 DNA polymerase (T7 exo-),
      and wild-type rat DNA polymerase beta in order to evaluate the selectivity of
      PMPA as an antiviral inhibitor. With a DNA/DNA or DNA/RNA 22/43-mer duplex, the
      diphosphate of PMPA (PMPApp) is as effective as ddATP in reactions catalyzed by
      HIV-1 reverse transcriptase in that both analogs have similar substrate
      specificity constants (kp/Kd) which are only 5-fold lower than dATP. In contrast,
      PMPApp is a much weaker inhibitor of the reaction catalyzed by T7 exo- (with the
      DNA/DNA 22/43-mer duplex) in that PMPApp has a 5 x 10(-4)-fold lower kp/Kd than
      ddATP and dATP. The lower kp/Kd of PMPApp is due to a 1000-2000-fold lower
      incorporation rate (kp) and a 35-45-fold lower binding constant (Kd). Similarly,
      PMPApp is 800-fold less inhibitory toward polymerase beta with the DNA/DNA 22/43
      mer duplex, whereas in studies with a single nucleotide gapped DNA (22-20/43-mer)
      PMPApp is 13-fold less inhibitory than ddATP. Although parallel studies will need
      to be performed using appropriate human polymerases, these results begin to
      define the mechanistic basis for the reported lower toxicity of PMPA in the
      treatment of AIDS.

PMID- 9765249
TI  - DNA secondary structure effects on DNA synthesis catalyzed by HIV-1 reverse
      transcriptase.
AB  - The effect of DNA secondary structure on polymerization catalyzed by human
      immunodeficiency virus (HIV-1) reverse transcriptase (RT) was studied using a
      synthetic 66-nucleotide DNA template containing a stable hairpin structure. Four
      RT pause sites were identified within the first half of the hairpin stem.
      Additionally, five weak pause sites within the second half of the stem and the
      loop of the hairpin were identified at low temperatures. These weak pause sites
      were relocated to the site of the first few stem base pairs of two new hairpins
      formed due to a change in DNA secondary structure. Each pause site was correlated
      with a high free energy barrier of melting the stem base pair. Pre-steady state
      kinetic analysis of single nucleotide incorporation showed that polymerization at
      each pause site occurred by both a fast phase (10-20 s-1) and a slow phase (0. 02
      0.07 s-1) during a single binding event. The reaction amplitudes of the fast
      phase were small (4-10% of enzyme sites), whereas the amplitudes of the slow
      phase were large (14-40%) at the pause sites. In contrast, only a single phase
      with a large reaction amplitude (32-50%) and a fast nucleotide incorporation rate
      (33-87 s-1) was observed at the non-pause sites. DNA substrates at all sites had
      similar dissociation rates (0.14-0.29 s-1) and overall binding affinity (16-86
      nM). These results suggest that the DNA substrates at pause sites were bound in
      both productive and non-productive states at the polymerase site of RT. The non
      productively bound DNA was slowly converted into a productive state upon melting
      of the next stem base pair without dissociation of the DNA from RT.

PMID- 9765250
TI  - Distinct mechanisms mediate the initial and sustained phases of integrin-mediated
      activation of the Raf/MEK/mitogen-activated protein kinase cascade.
AB  - Integrin-mediated adhesion to the extracellular matrix activates the canonical
      mitogen-activated protein kinase cascade, although the exact mechanism is not
      fully resolved. We show that integrin-mediated activation of Raf-1, an upstream
      regulator of mitogen-activated protein kinase, occurs in two phases. Efficient
      early activation of Raf required Raf-Ras interaction but was not affected by
      protein kinase C (PKC) inhibitors, while a lower, sustained level of activity was
      independent of Raf-Ras interaction but was reduced by PKC inhibitors. The
      combination of PKC inhibition and lack of Ras binding completely blocked integrin
      mediated Raf activity. The activity of a membrane-bound Raf mutant that is
      deficient in Ras binding (Raf-R89L-CAAX) was also regulated by adhesion. Raf-R89L
      CAAX activity was low in nonadherent cells, was rapidly stimulated to wild-type
      levels by cell adhesion, and remained at nearly maximal levels longer than wild
      type activity. The activation of wild-type and mutant Raf proteins was ablated by
      cytochalasin D, demonstrating that cytoskeletal organization is required for
      activation of Raf, even when targeted to the membrane. These data suggest
      distinct initial and sustained phases of integrin-mediated Raf activation that
      require Raf membrane localization and possibly PKC activity, respectively, and
      that integrin-mediated adhesion may regulate a cytoskeleton-associated factor(s)
      responsible for Raf activation.

PMID- 9765251
TI  - Promiscuous coupling of receptors to Gq class alpha subunits and effector
      proteins in pancreatic and submandibular gland cells.
AB  - Mice with deficiencies in one or more Gq class alpha subunit genes were used to
      examine the role of the alpha subunit in regulating Ca2+ signaling in pancreatic
      and submandibular gland cells. Western blot analysis showed that these cells
      express three of the four Gq class subunits, Galphaq, Galpha11, and Galpha14 but
      not Galpha15. Surprisingly, all parameters of Ca2+ signaling were identical in
      cells from wild type and four lines of mutant mice: 1) Galpha11-/-, 2) Galpha11-/
      /Galpha14-/-, 3) Galpha14-/-/Galpha15-/-, and 4) Galphaq-/-/Galpha15-/-. These
      parameters included the Kapp for several Gq class coupled receptors, induction of
      [Ca2+]i oscillations by weak stimulation, and a biphasic [Ca2+]i response by
      strong stimulation. Furthermore, Ca2+ release from internal stores and Ca2+ entry
      were not affected in cells from any of the mutant mice. We conclude that Galphaq,
      Galpha11, and Galpha14 promiscuously couple several receptors (m3 muscarinic,
      bombesin, cholecystokinin, and alpha1 adrenergic) to effector proteins that
      activate both Ca2+ release from internal stores and Ca2+ entry.

PMID- 9765252
TI  - Lack of tyrosine nitration by peroxynitrite generated at physiological pH.
AB  - Nitration of tyrosine residues of proteins has been suggested as a marker of
      peroxynitrite-mediated tissue injury in inflammatory conditions. The nitration
      reaction has been extensively studied in vitro by bolus addition of authentic
      peroxynitrite, an experimental approach hardly reflecting in vivo situations in
      which the occurrence of peroxynitrite is thought to result from continuous
      generation of .NO and O-2 at physiological pH. In the present study, we measured
      the nitration of free tyrosine by .NO and O-2 generated at well defined rates
      from the donor compound (Z)-1-[N-[3-aminopropyl]-N-[4-(3
      aminopropylammonio)butyl]-amino]- dia zen-1-ium-1,2-diolate] (spermine NONOate)
      and the xanthine oxidase reaction, respectively. The results were compared with
      the established nitration reaction triggered by authentic peroxynitrite. Bolus
      addition of peroxynitrite (1 mM) to tyrosine (1 mM) at pH 7.4 yielded 36.77 +/-
      1.67 microM 3-nitrotyrosine, corresponding to a recovery of about 4%. However,
      peroxynitrite formed from .NO and O-2, which were generated at equal rates (
      approximately 5 microM x min-1) from 1 mM spermine NONOate, 28 milliunits/ml
      xanthine oxidase, and 1 mM hypoxanthine was much less efficient (0.67 +/- 0.01
      microM; approximately 0.07% of total product flow). At O-2 fluxes exceeding the
      .NO release rates, 3-nitrotyrosine formation was below the detection limit of the
      high performance liquid chromatography method (<0.06 microM). Nitration was most
      efficient (approximately 0.3%) with the .NO donor alone, i.e. without concomitant
      generation of O-2. Nitration by .NO had a pH optimum of 8.2, increased
      progressively with increasing tyrosine concentrations (0.1-2 mM), and was not
      enhanced by NaHCO3 (up to 20 mM), indicating that it was mediated by .NO2 rather
      than peroxynitrite. Our results argue against peroxynitrite produced from .NO and
      O-2 as a mediator of tyrosine nitration in vivo.

PMID- 9765253
TI  - Hypo-osmotic shock of tobacco cells stimulates Ca2+ fluxes deriving first from
      external and then internal Ca2+ stores.
AB  - Hypo-osmotic shock of aequorin-transformed tobacco cells induces a biphasic
      cytosolic Ca2+ influx. Because both phases of Ca2+ entry are readily blocked by
      Ca2+ channel inhibitors, we conclude that the Ca2+ transients are mediated by
      Ca2+ channels. Evidence that the first but not second Ca2+ transient derives from
      external Ca2+ stores is that the first but not second influx is (i) eliminated by
      membrane-impermeable Ca2+ chelators, (ii) enlarged by supplementation of the
      medium with excess Ca2+, and (iii) reduced by the addition of competitive cations
      such as Mg2+ and Mn2+. Furthermore, entry of 45Ca during osmotic shock is
      prevented by inhibitors of the first but not second phase of Ca2+ entry. Evidence
      that the second wave of Ca2+ influx stems from release of intracellular Ca2+ is
      based on the above data plus observations that probable modulators of
      intracellular Ca2+ channels selectively block this phase of Ca2+ influx. Finally,
      a mechanism of communication between the two Ca2+ release pathways has become
      apparent, since perturbations that elevate or reduce the first Ca2+ transient
      lead to a compensating diminution/elevation of the second and vice versa. These
      data thus suggest that osmotic shock leads to the sequential opening of
      extracellular followed by intracellular Ca2+ stores and that these Ca2+ release
      pathways are internally compensated.

PMID- 9765254
TI  - Selective role for beta-protein kinase C in signaling for O-2 generation but not
      degranulation or adherence in differentiated HL60 cells.
AB  - A role for protein kinase C (PKC) isotypes is implicated in the activation of
      phagocytic cell functions. An antisense approach was used to selectively deplete
      beta-PKC, both betaI- and betaII-PKC, but not alpha-PKC, delta-PKC, or zeta-PKC
      in HL60 cells differentiated to a neutrophil-like phenotype (dHL60 cells).
      Depletion of beta-PKC in dHL60 cells elicited selective inhibition of O-2
      generation triggered by fMet-Leu-Phe, immune complexes, or phorbol myristate
      acetate, an activator of PKC. In contrast, neither ligand-elicited beta
      glucuronidase (azurophil granule) release nor adherence to fibronectin was
      inhibited by beta-PKC depletion. Ligand-induced phosphorylation of a subset of
      proteins was reduced in beta-PKC-depleted dHL60 cells. Phosphorylation of
      p47(phox) and translocation of p47(phox) to the membrane are essential for
      activation of the NADPH oxidase and generation of O-2. beta-PKC depletion had no
      effect on the level of p47(phox) in dHL60 cells but did significantly decrease
      ligand-induced phosphorylation of this protein. Furthermore, translocation of
      p47(phox) to the membrane in response to phorbol myristate acetate or fMet-Leu
      Phe was reduced in beta-PKC-depleted cells. These results indicate that beta-PKC
      is essential for signaling for O-2 generation but not cell adherence or azurophil
      degranulation. Depletion of beta-PKC inhibited ligand-induced phosphorylation of
      p47(phox), translocation of p47(phox) to the membrane, and activation of O-2
      generation.

PMID- 9765255
TI  - Platelet-derived growth factor-BB and thrombin generate positive and negative
      signals for human hepatic stellate cell proliferation. Role of a
      prostaglandin/cyclic AMP pathway and cross-talk with endothelin receptors.
AB  - Proliferation of myofibroblastic hepatic stellate cells (HSC) in response to
      growth factors is essential for the development of liver fibrosis. We have
      reported that prostaglandins (PG) and cyclic AMP (cAMP) inhibit growth of human
      HSC. This PG/cAMP pathway transduces the endothelin (ET) B-mediated
      antiproliferative effect of endothelin-1 (ET-1) and up-regulates ETB receptors.
      Here, we show that platelet-derived growth factor (PDGF)-BB and thrombin,
      although mitogenic, generate growth inhibitory PGE2 in myofibroblastic human HSC.
      The two peptides elicit early PGE2 and cAMP synthesis, and also promote delayed
      induction of cyclooxygenase (COX)-2. Both early and delayed production of PGE2
      counteract the mitogenic effect of PDGF-BB and thrombin because: (i) pretreatment
      with the COX inhibitor ibuprofen markedly enhances the mitogenic effect of both
      peptides; (ii) blocking early synthesis of PGE2 greatly enhances extracellular
      signal-regulated kinase (ERK) activation by both growth factors; (iii)
      enhancement of DNA synthesis by ibuprofen is only lost when the inhibitor is
      added after COX-2 induction has occurred. Finally, PDGF-BB and thrombin raise ETB
      receptors through the PG pathway. Thus, ibuprofen blunts growth factor-induced
      increase in ETB receptors. Up-regulation of the growth inhibitory ETB receptors
      by both mitogens may enhance the antiproliferative effect of ET-1 and thereby
      establish a negative feedback of their mitogenic effect. Our results shed light
      on novel growth inhibitory signals evoked by two mitogenic growth factors
      expressed during liver injury.

PMID- 9765256
TI  - Prostaglandin E2 Up-regulates HIV-1 long terminal repeat-driven gene activity in
      T cells via NF-kappaB-dependent and -independent signaling pathways.
AB  - Replication of human immunodeficiency virus type-1 (HIV-1) is highly dependent on
      the state of activation of the infected cells and is modulated by interactions
      between viral and host cellular factors. Prostaglandin E2 (PGE2), a pleiotropic
      immunomodulatory molecule, is observed at elevated levels during HIV-1 infection
      as well as during the course of other pathogenic infections. In 1G5, a Jurkat
      derived T cell line stably transfected with a luciferase gene driven by HIV-1
      long terminal repeat (LTR), we found that PGE2 markedly enhanced HIV-1 LTR
      mediated reporter gene activity. Experiments have been conducted to identify
      second messengers involved in this PGE2-dependent up-regulating effect on the
      regulatory element of HIV-1. In this study, we present evidence indicating that
      signal transduction pathways induced by PGE2 necessitate the participation of
      cyclic AMP, protein kinase A, and Ca2+. Experiments conducted with different HIV
      1 LTR-based vectors suggested that PGE2-mediated activation effect on HIV-1
      transcription was transduced via both NF-kappaB-dependent and -independent
      signaling pathways. The involvement of NF-kappaB in the PGE2-dependent activating
      effect on HIV-1 transcription was further confirmed using a kappaB-regulated
      luciferase encoding vector and by electrophoretic mobility shift assays. Results
      from Northern blot and flow cytometric analyses, as well as the use of a
      selective antagonist indicated that PGE2 modulation of HIV-1 LTR-driven reporter
      gene activity in studied T lymphoid cells is transduced via the EP4 receptor
      subtype. These results suggest that secretion of PGE2 by macrophages in response
      to infection or inflammatory activators could induce signaling events resulting
      in activation of proviral DNA present into T cells latently infected with HIV-1.

PMID- 9765257
TI  - Bacteriophage T7 DNA helicase binds dTTP, forms hexamers, and binds DNA in the
      absence of Mg2+. The presence of dTTP is sufficient for hexamer formation and DNA
      binding.
AB  - The role of Mg2+ in dTTP hydrolysis, dTTP binding, hexamer formation, and DNA
      binding was studied in bacteriophage T7 DNA helicase (4A' protein). The steady
      state kcat for the dTTPase activity was 200-300-fold lower in the absence of
      MgCl2, but the Km was only slightly affected. Direct dTTP binding experiments
      showed that the Kd of dTTP was unaffected, but the stoichiometry of dTTP binding
      was different in the absence of Mg2+. Two dTTPs were found to bind tightly in the
      absence of Mg2+ in contrast to three to four in the presence of Mg2+. In the
      presence of DNA there was little difference in the stoichiometry of dTTP binding
      to 4A'. These results indicate that Mg2+ is not necessary for dTTP binding, but
      Mg2+ is required for optimal hydrolysis of dTTP. Gel filtration of 4A' in the
      presence of dTTP without Mg2+ showed that Mg2+ was not necessary, and dTTP was
      sufficient for hexamer formation. The hexamers formed in the presence of dTTP
      without Mg2+ were capable of binding single-stranded DNA. However, the 4A'
      hexamers formed in the presence of dTDP with or without Mg2+ did not bind DNA,
      indicating that hexamer formation itself is not sufficient for DNA binding. The
      hexamers need to be in the correct conformation, in this case in the dTTP-bound
      state, to interact with the DNA. Thus, the gamma-phosphate of dTTP plays an
      important role in causing a conformational change in the protein that leads to
      stable interactions of 4A' with the DNA.

PMID- 9765258
TI  - Activation of protein kinase B/Akt is sufficient to repress the glucocorticoid
      and cAMP induction of phosphoenolpyruvate carboxykinase gene.
AB  - A rat hepatoma cell line, H4IIE, was stably transfected with a tamoxifen
      regulatable Akt-1 construct. Treatment of these cells with tamoxifen caused a
      rapid stimulation of Akt enzymatic activity that was comparable with the activity
      observed with the endogenous Akt after insulin stimulation. Prior studies have
      extensively documented that insulin can repress the glucocorticoid and cAMP
      stimulated increase in phosphoenolpyruvate carboxykinase (PEPCK) gene
      transcription. Activation of this regulatable Akt with tamoxifen was found to
      mimic the dominant inhibitory effect of insulin on PEPCK gene transcription. Dose
      response curves to insulin and tamoxifen demonstrated that this response was very
      sensitive to Akt activation although the maximal response observed with tamoxifen
      activation was slightly less than that observed with insulin, indicating that the
      response to insulin may also involve other signaling cascades. The regulation of
      PEPCK transcription via Akt was, like that previously described for insulin, not
      dependent upon 70 kDa S6 kinase activity in that it was not inhibited by
      rapamycin. Finally, the expression of a kinase dead Akt was able to partially
      inhibit the ability of insulin to stimulate this response. In summary, the
      present results indicate that activation of Akt alone is sufficient to repress
      the glucocorticoid and cAMP-stimulated increase in PEPCK gene transcription.

PMID- 9765259
TI  - The sulfuryl transfer mechanism. Crystal structure of a vanadate complex of
      estrogen sulfotransferase and mutational analysis.
AB  - Estrogen sulfotransferase (EST) catalyzes transfer of the 5'-sulfuryl group of
      adenosine 3'-phosphate 5'-phosphosulfate (PAPS) to the 3alpha-phenol group of
      estrogenic steroids such as estradiol (E2). The recent crystal structure of EST
      adenosine 3', 5'-diphosphate (PAP)- E2 complex has revealed that residues Lys48,
      Thr45, Thr51, Thr52, Lys106, His108, and Try240 are in position to play a
      catalytic role in the sulfuryl transfer reaction of EST (Kakuta Y., Pedersen, L.
      G., Carter, C. W., Negishi, M., and Pedersen, L. C. (1997) Nat. Struct. Biol. 4,
      904-908). Mutation of Lys48, Lys106, or His108 nearly abolishes EST activity,
      indicating that they play a critical role in catalysis. A present 2.2-A
      resolution structure of EST-PAP-vanadate complex indicates that the vanadate
      molecule adopts a trigonal bipyramidal geometry with its equatorial oxygens
      coordinated to these three residues. The apical positions of the vanadate
      molecule are occupied by a terminal oxygen of the 5'-phosphate of PAP (2.1 A) and
      a possible water molecule (2. 3 A). This water molecule superimposes well to the
      3alpha-phenol group of E2 in the crystal structure of the EST.PAP.E2 complex.
      These structures are characteristic of the transition state for an in-line
      sulfuryl transfer reaction from PAPS to E2. Moreover, residues Lys48, Lys106, and
      His108 are found to be coordinated with the vanadate molecule at the transition
      state of EST.

PMID- 9765260
TI  - Transcription factor AP-2gamma regulates murine adenosine deaminase gene
      expression during placental development.
AB  - Trophoblast cells are specialized extra-embryonic cells present only in eutherian
      mammals. They play a major role in the implantation and placentation processes.
      To understand better the molecular mechanisms that control the development and
      function of trophoblast cells, we sought to identify the transcription factors
      that regulate murine adenosine deaminase (ADA) gene expression in the placenta.
      Here we report a detailed characterization of a placenta-specific footprinting
      region (FP1) in the Ada placental regulatory element. The sequence of FP1 was
      mapped by DNase I footprinting and was found to match a consensus AP-2
      transcription factor-binding site. Electrophoretic mobility shift assays
      demonstrated that FP1 interacted with AP-2-like proteins. Further analysis using
      AP-2 antibody confirmed that AP-2 protein was indeed present in the placenta and
      bound to FP1. Mutation at the AP-2 site in FP1 abolished the ability of the Ada
      placental regulatory element to bind AP-2 proteins and failed to target
      chloramphenicol acetyltransferase reporter gene expression to placentas in
      transgenic mice, indicating that AP-2 is required for Ada expression in the
      placenta. In addition, RNase protection assays demonstrated that AP-2gamma was
      the predominant AP-2 family member expressed in the placenta. In situ
      hybridization analysis revealed that AP-2gamma expression was enriched in the
      trophoblast lineage throughout development, suggesting that AP-2gamma may be
      critical for trophoblast development and differentiation.

PMID- 9765261
TI  - An extended alpha-helix and specific amino acid residues opposite the DNA-binding
      surface of the cAMP response element binding protein basic domain are important
      for human T cell lymphotropic retrovirus type I Tax binding.
AB  - The human T cell lymphotropic retrovirus type I (HTLV-I) trans-activator, Tax,
      interacts specifically with the basic-domain/leucine-zipper (bZip) protein, cAMP
      response element binding protein (CREB), bound to the viral Tax-responsive
      element consisting of three imperfect 21-base pair repeats, each with a cAMP
      response element core flanked by G/C-rich sequences. Here, the minimal CREB-bZip
      necessary for Tax binding is shown to be composed of amino acid residues 280-341.
      The Tax-CREB interaction involves an uninterrupted and extended alpha-helix in
      CREB that spans most of its basic domain to include amino acid residues localized
      to the NH2 terminus of the DNA binding region. Mutational analyses indicate that
      three residues, Arg284, Met291, and Glu299 unique to this region of the
      CREB/activating transcription factor-1 subfamily of bZip proteins, constitute the
      contact surface for Tax. Amino acid substitutions in these positions had little
      impact on CREB-bZip binding to DNA but abrogated its binding to Tax. Each of the
      contact residues for Tax are spaced approximately two helical turns apart on the
      side of the bZip helix directly opposite to that of the invariant DNA-binding
      residues. Molecular modeling reveals the Tax-contact residues to be near the
      minor groove of the G/C-rich DNA in the 21-base pair repeat. They most likely
      position Tax for minor groove contact with the G/C-rich sequences.

PMID- 9765262
TI  - The gene glvA of Bacillus subtilis 168 encodes a metal-requiring, NAD(H)
      dependent 6-phospho-alpha-glucosidase. Assignment to family 4 of the
      glycosylhydrolase superfamily.
AB  - The gene glvA (formerly glv-1) from Bacillus subtilis has been cloned and
      expressed in Escherichia coli. The purified protein GlvA (449 residues, Mr =
      50,513) is a unique 6-phosphoryl-O-alpha-D-glucopyranosyl:phosphoglucohydrolase
      (6-phospho-alpha-glucosidase) that requires both NAD(H) and divalent metal (Mn2+,
      Fe2+, Co2+, or Ni2+) for activity. 6-Phospho-alpha-glucosidase (EC 3.2.1.122)
      from B. subtilis cross-reacts with polyclonal antibody to maltose 6-phosphate
      hydrolase from Fusobacterium mortiferum, and the two proteins exhibit amino acid
      sequence identity of 73%. Estimates for the Mr of GlvA determined by SDS
      polyacrylamide gel electrophoresis (51,000) and electrospray-mass spectroscopy
      (50,510) were in excellent agreement with the molecular weight of 50,513 deduced
      from the amino acid sequence. The sequence of the first 37 residues from the N
      terminus determined by automated analysis agreed precisely with that predicted by
      translation of glvA. The chromogenic and fluorogenic substrates, p-nitrophenyl
      alpha-D-glucopyranoside 6-phosphate and 4-methylumbelliferyl-alpha-D
      glucopyranoside 6-phosphate were used for the discontinuous assay and in situ
      detection of enzyme activity, respectively. Site-directed mutagenesis shows that
      three acidic residues, Asp41, Glu111, and Glu359, are required for GlvA activity.
      Asp41 is located at the C terminus of a betaalphabeta fold that may constitute
      the dinucleotide binding domain of the protein. Glu111 and Glu359 may function as
      the catalytic acid (proton donor) and nucleophile (base), respectively, during
      hydrolysis of 6-phospho-alpha-glucoside substrates including maltose 6-phosphate
      and trehalose 6-phosphate. In metal-free buffer, GlvA exists as an inactive
      dimer, but in the presence of Mn2+ ion, these species associate to form the
      NAD(H)-dependent catalytically active tetramer. By comparative sequence alignment
      with its homologs, the novel 6-phospho-alpha-glucosidase from B. subtilis can be
      assigned to the nine-member family 4 of the glycosylhydrolase superfamily.

PMID- 9765263
TI  - Structure-based minimization of transforming growth factor-alpha (TGF-alpha)
      through NMR analysis of the receptor-bound ligand. Design, solution structure,
      and activity of TGF-alpha 8-50.
AB  - The investigation of a N-terminally truncated human transforming growth factor
      alpha (TGF-alpha; residues 8-50) has been completed to determine the contribution
      of the N terminus to receptor binding and activation. The deletion protein was
      proposed and designed through study of NMR relaxation and nuclear Overhauser
      enhancement data obtained from the TGF-alpha-epidermal growth factor (EGF)
      receptor complex, which indicated that the residues N-terminal to the A loop
      remain flexible in receptor-bound TGF-alpha and thus suggested their lack of
      involvement in receptor binding (Hoyt, D. W., Harkins, R. N., Debanne, M. T.,
      O'Connor-McCourt, M., and Sykes, B. D. (1994) Biochemistry 33, 15283-15292;
      McInnes, C., Hoyt, D. W., Harkins, R. N., Pagila, R. N., Debanne, M. T., O'Connor
      McCourt, M., and Sykes, B. D. (1996) J. Biol. Chem. 271, 32204-32211). TGF-alpha
      8-50 was shown to have approximately 10-fold lower affinity for the receptor than
      the native molecule in an assay quantifying the ability to compete with EGF for
      binding and to have a similar reduction in activity as indicated by a cell
      proliferation assay. NMR solution structural calculations on this molecule
      demonstrate correct formation of the three disulfide bonds of TGF-alpha 8-50 and
      have established the presence of native secondary structure in the B and C loops
      of the protein. However, some perturbation of the global fold with respect to the
      orientation of the subdomains was observed. These results suggest that although
      the N-terminal residues do not contribute directly to binding, they make a
      significant contribution in defining the conformation of the growth factor, which
      is required for complete binding and activity and is therefore significant in
      terms of producing native folding of TGF-alpha. They also show that information
      obtained from the receptor-bound ligand can be used to guide the design and
      minimization of TGF-alpha analogues. The implications of the study of TGF-alpha 8
      50 for the design and synthesis of reductants of this growth factor are therefore
      discussed.

PMID- 9765264
TI  - Definition and redesign of the extended substrate specificity of granzyme B.
AB  - Granzyme B is a protease involved in the induction of rapid target cell death by
      cytotoxic lymphocytes. Definition of the substrate specificity of granzyme B
      allows for the identification of in vivo substrates in this process. By using the
      combinatorial methods of synthetic substrate libraries and substrate-phage
      display, an optimal substrate for granzyme B that spans over six subsites was
      determined to be Ile-Glu-Xaa-(Asp downward arrowXaa)-Gly, with cleavage of the
      Asp downward arrowXaa peptide bond. Granzyme B proteolysis was shown to be highly
      dependent on the length and sequence of the substrate, supporting the role of
      granzyme B as a regulatory protease. Arginine 192 was identified as a determinant
      of P3-Glu and P1-Asp substrate specificity. Mutagenesis of arginine 192 to
      glutamate reversed the preference for negatively charged amino acids at P3 to
      positively charged amino acids. The preferred substrate sequence matches the
      activation sites of caspase 3 and caspase 7 and thus is consistent with the role
      of granzyme B in activation of these proteases during apoptosis. The caspase
      substrate poly(ADP)-ribose polymerase is cleaved by granzyme B in a cell-free
      assay at two sites that resemble the granzyme B specificity determined by the
      combinatorial methods. Many caspase substrates contain granzyme B cleavage sites
      and are proposed as potential granzyme B targets, suggesting a redundant function
      with certain caspases.

PMID- 9765265
TI  - Identification of protein-arginine N-methyltransferase as 10
      formyltetrahydrofolate dehydrogenase.
AB  - S-Adenosylmethionine:protein-arginine N-methyltransferase (EC 2.1.1. 23; protein
      methylase I) transfers the methyl group of S-adenosyl-L-methionine to an arginine
      residue of a protein substrate. The homogeneous liver protein methylase I was
      subjected to tryptic digestion followed by reverse phase high performance liquid
      chromatography (HPLC) separation and either "on-line" mass spectrometric
      fragmentation or "off-line" Edman sequencing of selected fractions. Data base
      searching of both the mass spectrometric and Edman sequencing data from several
      peptides identified the protein methylase as 10-formyltetrahydrofolate
      dehydrogenase (EC 1.5.1.6; Cook, R. J., Lloyd, R. S., and Wagner, C. (1991) J.
      Biol. Chem. 266, 4965-4973; Swiss accession number). This identification was
      confirmed by comparative HPLC tryptic peptide mapping and affinity chromatography
      of the methylase on the 5-formyltetrahydrofolate-Sepharose affinity gel used to
      purify the dehydrogenase. The purified rat liver methylase had approximately 33%
      of the 10-formyltetrahydrofolate dehydrogenase and 36% of the aldehyde
      dehydrogenase activity as compared with the recombinant dehydrogenase, which also
      had protein methylase I activity. Polyclonal antibodies against recombinant
      dehydrogenase reacted with protein methylase I purified either by polyacrylamide
      gel electrophoresis or 5-formyltetrahydrofolate affinity chromatography. In each
      instance there was only a single immunoreactive band at a molecular weight of
      approximately 106,000. Together, these results confirm the co-identity of protein
      arginine methyltransferase and 10-formyltetrahydrofolate dehydrogenase.

PMID- 9765266
TI  - Receptor-regulated translocation of endothelial nitric-oxide synthase.
AB  - The endothelial nitric-oxide synthase (eNOS) is activated by transient increases
      in intracellular Ca2+ elicited by stimulation of diverse receptors, including
      bradykinin B2 receptors on endothelial cells. eNOS and B2 receptors are targeted
      to specialized signal-transducing domains in the plasma membrane termed
      plasmalemmal caveolae. Targeting to caveolae facilitates eNOS activation
      following receptor stimulation, but in resting cells, eNOS is tonically inhibited
      by its interactions with caveolin, the scaffolding protein in caveolae. We used a
      quantitative approach exploiting immunofluorescence microscopy to investigate
      regulation of the subcellular distribution of eNOS in endothelial cells by
      bradykinin and Ca2+. In resting cells, most of the eNOS is localized at the cell
      membrane. However, within 5 min following addition of bradykinin, nearly all the
      eNOS translocates to structures in the cell cytosol; following more protracted
      incubations with bradykinin, most of the cytosolic enzyme subsequently
      translocates back to the cell membrane. The bradykinin-induced internalization of
      eNOS is completely abrogated by the intracellular Ca2+ chelator BAPTA;
      conversely, Ca2+-mobilizing drugs and agonists promote eNOS translocation. These
      results establish that eNOS targeting to the membrane is labile and is subject to
      receptor-regulated Ca2+-dependent reversible translocation, providing another
      point for regulation of NO-dependent signaling in the vascular endothelium.

PMID- 9765267
TI  - Apoptosis and activation of the sphingomyelin-ceramide pathway induced by
      oxidized low density lipoproteins are not causally related in ECV-304 endothelial
      cells.
AB  - Oxidized low density lipoproteins (oxLDL) are thought to play a central role in
      the development of atherosclerosis. Toxic concentrations of mildly oxidized LDL
      elicit massive apoptosis of endothelial cells (Escargueil-Blanc, I., Meilhac, O.,
      Pieraggi, M. T. , Arnal J. F., Salvayre, R., Negre-Salvayre, A. (1997)
      Arterioscler. Thromb. Vasc. Biol. 17, 331-339). Since the lipid mediator ceramide
      emerged as a potent inducer of apoptosis, we aimed at investigating the
      occurrence of ceramide formation and its potential role in oxLDL-induced
      apoptosis. In ECV-304 endothelial cells, toxic concentrations of oxLDL triggered
      an early activation of the sphingomyelin-ceramide pathway, as shown by both
      sphingomyelin hydrolysis and ceramide formation. N-Tosyl-L-phenylalanyl
      chloromethyl ketone (TPCK) and dichloroisocoumarin (DCIC), two serine-protease
      inhibitors (serpins), blocked the oxLDL-induced ceramide generation but,
      unexpectedly, did not inhibit the oxLDL-induced apoptosis. Conversely, treatment
      of endothelial cells by bacterial sphingomyelinase, under conditions effectively
      generating ceramide, did not induce apoptosis. In contrast, short-chain permeant
      C2- and C6-ceramides elicited apoptosis of ECV-304. However, the mechanisms of
      apoptosis triggered by C2-ceramide and by oxLDL were (at least in part)
      different, because C2-ceramide-induced apoptosis was calcium-independent, whereas
      oxLDL-induced apoptosis was calcium-dependent. In conclusion, it is suggested
      that oxLDL-induced apoptosis is calcium-dependent but independent of the
      activation of the sphingomyelin-ceramide pathway and that the toxic effect of
      short chain permeant ceramides is calcium-independent and does not mimic the
      effect of natural ceramides induced by oxLDL.

PMID- 9765268
TI  - The I domain of integrin leukocyte function-associated antigen-1 is involved in a
      conformational change leading to high affinity binding to ligand intercellular
      adhesion molecule 1 (ICAM-1).
AB  - On T cells the leukocyte integrin leukocyte function-associated antigen-1 (LFA-1)
      (CD11a/CD18) can be induced to bind its ligand intercellular adhesion molecule 1
      (ICAM-1) (CD54) either by increasing the affinity of the receptor with Mg2+ and
      EGTA or by receptor clustering following activation with phorbol ester. The
      existence of these two adhesion-inducing pathways implies that alternative
      mechanisms might exist by which LFA-1 engages ICAM-1. The LFA-1 alpha subunit I
      domain contains a major binding site for ICAM-1. In this study we show that
      soluble LFA-1 I domain blocks ICAM-1 binding of the high affinity Mg2+-induced
      form of LFA-1 but not the phorbol ester-induced form. Under conditions of Mg2+
      activation, the soluble I domain also prevents expression of an activation
      dependent epitope on LFA-1, implying that it inhibits a conformational change
      necessary for conversion to the high affinity form of this integrin. In addition,
      the binding of Mg2+-activated LFA-1 to ICAM-1 is blocked by peptides covering the
      alpha4-beta3 loop, the beta3-alpha5 loop, and the alpha5 helix of the I domain,
      whereas none of the peptides tested blocks phorbol ester-mediated adhesion. The
      blocking peptides localize to the same face of the crystal structure of the LFA-1
      I domain and define an area that, during activation, may be involved in
      association of the I domain with another region of LFA-1, potentially the beta
      propeller domain. This is the first evidence linking a structural domain of an
      integrin, in this case the I domain, with a particular activation mechanism.

PMID- 9765269
TI  - Effects of mutations in the gamma-phosphate binding site of myosin on its motor
      function.
AB  - The role of the highly conserved residues in the gamma-phosphate binding site of
      myosin upon myosin motor function was studied. Each of five residues (Ser181,
      Lys185, Asn235, Ser236, and Arg238) in smooth muscle myosin was mutated. K185Q
      has neither a steady state ATPase nor an initial Pi burst. Although ATP and actin
      bind to K185Q, it is not dissociated from actin by ATP. These results indicate
      that the hydrolysis of bound ATP by K185Q is inhibited. S236T has nearly normal
      basal Mg2+-ATPase activity, initial Pi burst, ATP-induced enhancement of
      intrinsic tryptophan fluorescence, and ATP-induced dissociation from actin.
      However, the actin activation of the Mg2+-ATPase activity and actin translocation
      of S236T were blocked. In contrast S236A has nearly normal enzymatic properties
      and actin-translocating activity. These results indicate that 1) the hydroxyl
      group of Ser236 is not critical as an intermediary of proton transfer during the
      ATP hydrolysis step, and 2) the bulk of the extra methyl group of the threonine
      residue in S236T blocks the acceleration of product release from the active site
      by actin. Arg238, which interacts with Glu459 at the Switch II region, was
      mutated to Lys and Ile, respectively. R238K has essentially normal enzymatic
      activity and motility. In contrast, R238I does not hydrolyze ATP or support
      motility, although it still binds ATP. These results indicate that the charge
      interaction between Glu459 and Arg238 is critical for ATP hydrolysis by myosin.
      Other mutants, S181A, S181T, and N235I, showed nearly normal enzymatic and motile
      activity.

PMID- 9765270
TI  - AKAP79 inhibits calcineurin through a site distinct from the immunophilin-binding
      region.
AB  - Targeting of protein kinases and phosphatases provides additional specificity to
      substrate selectivity in cellular signaling. In the case of the Ca2+/calmodulin
      dependent protein phosphatase calcineurin, AKAP79 has been shown to bind
      calcineurin and inhibit its activity in vitro (Coghlan, V., Perrino, B. A.,
      Howard, M., Langeberg, L. K., Hicks, J. B., Gallatin, W. M., and Scott, J. D.
      (1995) Science 267, 108-111). In the present study, we characterized the binding
      regions on calcineurin A (CnA) and AKAP79 that are important for this
      interaction. Residues 30-98 and 311-336 on CnA, and residues 108-280 on AKAP79
      were found to be important for binding. The binding of CnA by AKAP79 does not
      require the calcineurin B subunit, and occurs in a region distinct from where the
      immunosuppressant-immunophilin complex bind. AKAP79 also bound to CnA in cells
      transfected with AKAP79 and CnA. To determine the function of AKAP79-calcineurin
      interaction in intact cells, we measured the dephosphorylation and subsequent
      activation of NFAT, a transcription factor that is a substrate for calcineurin.
      Overexpression of AKAP79 inhibited NFAT dephosphorylation, resulting in a
      decrease in NFAT activation. These results demonstrated that AKAP79 can bind to
      and inhibit calcineurin activity in vivo, suggesting a physiological role for
      AKAP79-calcineurin interaction in NFAT-mediated signaling.

PMID- 9765271
TI  - Characterization of the murine fatty acid transport protein gene and its insulin
      response sequence.
AB  - Fatty acid transport protein (FATP) was identified by expression cloning
      strategies (Schaffer, J. E., and Lodish, H. F. (1994) Cell 79, 427-436) and shown
      by transfection analysis to catalyze the transfer of long-chain fatty acids
      across the plasma membrane of cells. It is expressed highly in tissues exhibiting
      rapid fatty acid metabolism such as skeletal muscle, heart, and adipose. FATP
      mRNA levels are down-regulated by insulin in cultured 3T3-L1 adipocytes and up
      regulated by nutrient depletion in murine adipose tissue (Man, M. Z., Hui, T. Y.,
      Schaffer, J. E., Lodish, H. F., and Bernlohr, D. A. (1996) Mol. Endocrinol. 10,
      1021-1028). To determine the molecular mechanism of insulin regulation of FATP
      transcription, we have isolated the murine FATP gene and its 5'-flanking
      sequences. The FATP gene spans approximately 16 kilobases and contains 13 exons,
      of which exon 2 is alternatively spliced. S1 nuclease and RNase protection assays
      revealed the presence of multiple transcription start sites; the DNA sequence
      upstream of the predominant transcription start sites lacks a typical TATA box.
      By transient transfection assays in 3T3-L1 adipocytes, the inhibitory action of
      insulin on FATP transcription was localized to a cis-acting element with the
      sequence 5'-TGTTTTC-3' from -1347 to -1353. This sequence is very similar to the
      insulin response sequence found in the regulatory region of other genes
      negatively regulated by insulin such as those encoding phosphoenolpyruvate
      carboxykinase, tyrosine aminotransferase, and insulin-like growth factor-binding
      protein 1. Fluorescence in situ hybridization analysis revealed that the murine
      FATP gene is localized to chromosome 8, band 8B3.3. Interestingly, this region of
      chromosome 8 contains a cluster of three other genes important for fatty acid
      homeostasis, lipoprotein lipase, the mitochondrial uncoupling protein 1 (UCP1)
      and sterol regulatory element-binding protein 1. These results characterize the
      murine FATP gene and its insulin responsiveness as well as present a framework
      for future studies of its role in lipid metabolism, obesity, and type II diabetes
      mellitus.

PMID- 9765272
TI  - Calmodulin-dependent regulation of inducible and neuronal nitric-oxide synthase.
AB  - Neuronal and endothelial nitric-oxide synthases depend upon Ca2+/calmodulin for
      activation, whereas the activity of the inducible nitric-oxide synthase is Ca2+
      independent, presumably due to tightly bound calmodulin. To study these different
      mechanisms, a series of chimeras derived from neuronal and inducible nitric-
      oxide synthases were analyzed. Chimeras containing only the oxygenase domain,
      calmodulin-binding region, or reductase domain of inducible nitric-oxide synthase
      did not confer significant Ca2+-independent activity. However, each chimera was
      more sensitive to Ca2+ than the neuronal isoform. The calmodulin-binding region
      of inducible nitric-oxide synthase with either its oxygenase or reductase domains
      resulted in significant, but not total, Ca2+-independent activity. Co
      immunoprecipitation experiments showed no calmodulin associated with the former
      chimera in the absence of Ca2+. Trifluoperazine also inhibited this chimera in
      the absence of Ca2+. The combined interactions of calmodulin bound to inducible
      nitric-oxide synthase calmodulin-binding region with the oxygenase domain may be
      weaker than with the reductase domain. Thus, Ca2+-independent activity of
      inducible nitric-oxide synthase appears to result from the concerted interactions
      of calmodulin with both the oxygenase and reductase domains in addition to the
      canonical calmodulin-binding region. The neuronal isoform is not regulated by a
      unique autoinhibitory element in its reductase domain.

PMID- 9765273
TI  - The dependence of membrane permeability by the antibacterial peptide cecropin B
      and its analogs, CB-1 and CB-3, on liposomes of different composition.
AB  - A natural antibacterial peptide, cecropin B (CB), and designed analogs, CB-1 and
      CB-3, were synthesized. The three peptides have different structural
      characteristics, with CB having one hydrophobic and one amphipathic alpha-helix,
      CB-1 having two amphipathic alpha-helices, and CB-3 having two hydrophobic alpha
      helices. These differences were used as the rationale for a study of their
      efficacy in breaking liposomes with different combinations of phosphatidic acid
      and phosphatidylcholine. Biosensor binding measurements and encapsulating dye
      leakage studies showed that the higher binding affinity of CB and CB-1 to the
      polar heads of lipids is not necessary for the peptides to be more effective at
      lysing lipid bilayers, especially when liposomes have a higher phosphatidic acid
      content. Kinetic studies, by intrinsic and extrinsic fluorescence stopped-flow
      measurements, revealed two transitional steps in liposome breakage by CB and CB
      1, although only one kinetic step was found for CB-3. Circular dichroism stopped
      flow measurements, monitoring the formation of secondary structure in the
      peptides, found one kinetic step for the interaction of all of the peptides with
      the liposomes. Also, the alpha-helical motif of the peptides was maintained after
      interacting with the liposomes. Based on these results, the mechanisms of
      liposome lysis by CB, CB-1, and CB-3 are discussed.

PMID- 9765274
TI  - Amino acid residues in thrombin-sensitive region and first epidermal growth
      factor domain of vitamin K-dependent protein S determining specificity of the
      activated protein C cofactor function.
AB  - Human protein S (PS) potentiates the anticoagulant activity of human but not
      bovine activated protein C (APC), whereas bovine PS is a cofactor to APC from
      both species. The structural requirements for the specificity of the APC cofactor
      function of human PS are located in its thrombin-sensitive region (TSR) and the
      first epidermal growth factor (EGF1)-like module. To elucidate which residues in
      these two modules determine the specificity of the APC cofactor activity, 41
      human PS mutants were expressed. All mutants were cofactors to human APC and some
      also to bovine APC. Residues in TSR (positions 49 and 52) and EGF1 (residues 97
      and 106) together determined the specificity of the APC cofactor function,
      whereas substitution of individual residues did not change specificity. Bovine
      PS, and mutants expressing cofactor activity to bovine APC, stimulated
      phospholipid binding of bovine APC. In contrast, human PS and mutants lacking
      cofactor activity to bovine APC failed to support binding of bovine APC to
      phospholipids. These data indicate that residues in TSR and EGF1 cause the
      specificity of the APC cofactor activity and support the concept that key
      residues in these two modules interact with APC on the phospholipid surface.

PMID- 9765275
TI  - The human WD repeat protein WAIT-1 specifically interacts with the cytoplasmic
      tails of beta7-integrins.
AB  - Integrins of the beta7 subfamily, alpha4 beta7 and alphaE beta7, contribute to
      lymphocyte homing and to the development of protective or autoreactive immune
      responses at mucosal sites. The beta subunits of integrins are considered
      important for regulation of stimulated cell adhesion and adhesion-dependent
      signal transduction. Using a yeast interaction trap screen, a human WD repeat
      protein, termed WAIT-1, was isolated that interacts with the integrin beta7
      cytoplasmic tail and is homologous to mouse EED and Drosophila ESC proteins. WAIT
      1 also binds to the cytoplasmic domains of alpha4 and alphaE but not to those of
      integrin beta1, beta2, and alphaL subunits. Association of WAIT-1 and beta7
      integrin was confirmed by coprecipitation from transiently transfected 293 cells.
      The binding site for WAIT-1 was mapped to a short membrane-proximal region of the
      beta7 cytoplasmic tail with Tyr-735 being of critical importance. Northern blot
      analysis revealed multiple WAIT-1-related transcripts with differential
      expression in circulating leukocytes, tissue-resident cells of diverse origin,
      and lymphoid malignancies. These results suggest that WAIT-1, together with the
      recently identified RACK1, may define a novel subfamily of WD repeat proteins
      that interact with distinct subsets of integrin cytoplasmic tails and may act as
      specific regulators of integrin function.

PMID- 9765276
TI  - Interleukin-17-induced gene expression in articular chondrocytes is associated
      with activation of mitogen-activated protein kinases and NF-kappaB.
AB  - This study examines intracellular signaling events associated with the activation
      of chondrocytes by the cytokine interleukin-17 (IL-17). Stimulation of normal
      human articular chondrocytes with IL-17 induced nitric oxide (NO) production,
      concomitant with an increase in transcripts and de novo translation products of
      the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) genes.
      Several other genes associated with inflammation and cartilage degradation, such
      as IL-1beta, IL-6, and stromelysin, were also up-regulated in IL-17-treated
      chondrocytes. Among signaling events displaying early response to IL-17 in
      chondrocytes were the mitogen-activated protein (MAP) kinases ERK1, ERK2, JNK,
      and p38. DNA binding activity of NF-kappaB was also significantly induced. IL-17
      effects on NO release, as well as iNOS, COX-2, and IL-6 protein expression, were
      inhibited by the anti-inflammatory drug dexamethasone. Importantly, dexamethasone
      blunted IL-17-dependent activation of MAP kinases, suggesting a mechanistic
      relationship between these activities and the aforementioned gene expression
      responses. Similar effects of a lesser extent were observed with the p38-specific
      inhibitor SB203580. These results suggest that IL-17 activation of chondrocytes
      is associated with and depends at least in part on the activation of MAP kinases
      and NF-kappaB.

PMID- 9765277
TI  - Sp1 and Sp3 regulate transcriptional activity of the facilitative glucose
      transporter isoform-3 gene in mammalian neuroblasts and trophoblasts.
AB  - The murine facilitative glucose transporter isoform 3 (Glut 3) is developmentally
      regulated and is predominantly expressed in neurons and trophoblasts. Employing
      the primer extension and RNase protection assays, the transcription start site
      (denoted as +1) of the murine Glut 3 gene was localized to 305 base pairs (bp) 5'
      to the ATG translation start codon. Transient transfection assays in N2A, H19-7
      neuroblasts, and HRP.1 trophoblasts using sequential 5'-deletions of the murine
      Glut 3-luciferase fusion gene indicated that the -203 to +237 bp region with
      reference to the transcriptional start site contained promoter activity.
      Repressor function was limited to the -137 to -130 bp region within the
      transcriptional activation domain. The nuclear factors Sp1 and Sp3 bound this GC
      rich region in N2A, H19-7, and HRP.1 cells. Dephosphorylation of Sp1 was
      essential for Glut 3 DNA binding. The related Sp3 protein also bound this same
      region of mouse Glut 3 in all three cell lines. Mutations of the Sp1-binding site
      employed in transient transfection and mobility shift assays confirmed the nature
      of the DNA-binding proteins, while supershift assays with anti-Sp1 and anti-Sp3
      IgGs characterized the differences in the two DNA-binding proteins. Co
      transfection of the Glut 3-luciferase fusion gene with or without mutations of
      the Sp1-binding site along with the Sp1 or Sp3 expression vectors in Drosophila
      SL2 cells confirmed a reciprocal effect, with Sp1 suppressing and Sp3 activating
      Glut 3 gene transcription.

PMID- 9765279
TI  - Replication protein A stimulates long patch DNA base excision repair.
AB  - Two pathways for completion of DNA base excision repair (BER) have recently
      emerged. In one, called short patch BER, only the damaged nucleotide is replaced,
      whereas in the second, known as long patch BER, the monobasic lesion is removed
      along with additional downstream nucleotides. Flap endonuclease 1, which
      preferentially cleaves unannealed 5'-flap structures in DNA, has been shown to
      play a crucial role in the long patch mode of repair. This nuclease will
      efficiently release 5'-terminal abasic lesions as part of an intact
      oligonucleotide when cleavage is combined with strand displacement synthesis.
      Further gap filling and ligation complete repair. We reconstituted the final
      steps of long patch base excision repair in vitro using calf DNA polymerase
      epsilon to provide strand displacement synthesis, human flap endonuclease 1, and
      human DNA ligase I. Replication protein A is an important constituent of the DNA
      replication machinery. It also has been shown to interact with an early component
      of base excision repair: uracil glycosylase. Here we show that human replication
      protein A greatly stimulates long patch base excision repair.

PMID- 9765278
TI  - Cyclic GMP and cGMP-binding phosphodiesterase are required for interleukin-1
      induced nitric oxide synthesis in human articular chondrocytes.
AB  - This study addressed the role of guanylyl cyclase (GC) and phosphodiesterase
      (PDE) in interleukin (IL)-1 activation of human articular chondrocytes. The GC
      inhibitors LY83583 and methylene blue dose-dependently inhibited IL-1-induced
      nitric oxide (NO) production, inducible NO synthase (iNOS) protein, and mRNA
      expression. These effects of GC inhibition were consistent with the rapid
      induction of cGMP by IL-1, which reached maximal levels after 5 min. The effects
      of GC inhibitors were selective as they did not reduce IL-1-induced
      cyclooxygenase II protein and mRNA. An inhibitor specific for soluble GC did not
      affect IL-1-induced NO production, and activators of soluble GC did not induce
      NO. However, the expression of iNOS mRNA was induced by atrial natriuretic
      peptide (ANP) and C-type natriuretic peptide (CNP), activators of particulate GC,
      indicating that particulate rather than soluble guanylyl cyclases were involved
      in iNOS induction. The expression of iNOS mRNA and the production of NO were
      induced by a slowly hydrolyzable analog of cGMP, 8-bromo-cGMP, but not by
      nonhydrolyzable analog, dibutyryl cGMP, suggesting that PDE rather than cGMP
      dependent protein kinase mediates the cGMP effects. Chondrocytes contained
      extensive cGMP PDE activity. This had PDE5 biochemical features and an inhibitor
      profile consistent with PDE5. Furthermore, the nonisoformspecific PDE inhibitor
      IBMX and PDE5-specific inhibitors suppressed IL-1-induced NO release and iNOS
      mRNA expression. PDE5 mRNA was constitutively expressed in chondrocytes. In
      addition to increasing PDE5 activities, IL-1 treatment reduced the sensitivity of
      PDE5 to several pharmacological inhibitors by up to 50-fold. In summary,
      inhibitors of either GC or PDE5 prevented IL-1 induction of iNOS; IL-1 increased
      the rates of both cGMP generation and hydrolysis; and exogenous PDE hydrolyzable
      cGMP analog induced iNOS and NO. These results suggest that increased cGMP
      metabolic flux is sufficient to induce iNOS, and GC and PDE5 activities are
      required for IL-1 induction of iNOS expression via increases in coupled cGMP
      synthesis and hydrolysis.

PMID- 9765280
TI  - Identification of native atrial G-protein-regulated inwardly rectifying K+
      (GIRK4) channel homomultimers.
AB  - G-protein-regulated inwardly rectifying K+ (GIRK) channels play critical
      inhibitory roles throughout the nervous system, heart, and pancreas. They are
      believed to be heterotetramers consisting of GIRK1 (Kir3.1) and either GIRK2
      (Kir3.2), GIRK3 (Kir3.3), or GIRK4 (Kir3.4) subunits. The GIRK1 subunit is
      hypothesized to be critical to form GIRK channels with normal channel kinetics
      based on heterologous expression studies. However, GIRK2 and GIRK3 proteins are
      present in areas of the brain where no GIRK1 has been detected. Here we
      demonstrate that GIRK tetramers lacking GIRK1 can be purified from bovine heart
      atria. We have found that only half of GIRK4 is purified as the GIRK1-GIRK4
      heterotetramer, whereas the remaining GIRK4 forms a high molecular weight, SDS
      resistant complex that does not contain GIRK1. These GIRK4 complexes, most likely
      GIRK4 homotetramers, were previously not seen because of their aberrant migration
      on SDS-polyacrylamide gels. We propose that all of GIRK1 and half of GIRK4
      proteins in atria combine to form the heterotetramer IKACh, whereas the remaining
      GIRK4 forms a novel tetrameric complex. GIRK4 homotetramers form channels with
      unusual single channel behavior, and their contribution to native currents
      requires further investigation.

PMID- 9765281
TI  - Hypoglycemia-associated hyperammonemia caused by impaired expression of ornithine
      cycle enzyme genes in C/EBPalpha knockout mice.
AB  - Ammonia produced by amino acid metabolism is detoxified through conversion into
      urea by the ornithine cycle in the liver, whereas carbon skeletons of amino acids
      are converted to glucose by gluconeogenic enzymes. Promoter and enhancer
      sequences of several genes for ornithine cycle enzymes interact with members of
      the CCAAT/enhancer-binding protein (C/EBP) transcription factor family.
      Disruption of the C/EBPalpha gene in mice causes hypoglycemia associated with the
      impaired expression of gluconeogenic enzymes. Here we examined the expression of
      ornithine cycle enzyme genes in the livers of C/EBPalpha-deficient mice. mRNA
      levels for the first, third, fourth, and fifth enzymes of five enzymes in the
      cycle were decreased in C/EBPalpha-deficient mice. Protein levels for the first,
      second, fourth, and fifth enzymes were also decreased. In situ hybridization
      analysis revealed that the enzyme mRNAs were distributed normally in the
      periportal region but were disordered in C/EBPalpha-deficient mice with
      relatively higher mRNA levels in the midlobular region. Blood ammonia
      concentrations in the mutant mice were severalfold higher than in wild-type mice.
      Thus, C/EBPalpha is crucial for ammonia detoxification by ornithine cycle enzymes
      and for coordination of gluconeogenesis and urea synthesis.

PMID- 9765282
TI  - Bone morphogenetic protein-1 processes the NH2-terminal propeptide, and a furin
      like proprotein convertase processes the COOH-terminal propeptide of pro
      alpha1(V) collagen.
AB  - Bone morphogenetic protein-1 (BMP-1) plays key roles in regulating the deposition
      of vertebrate extracellular matrix; it is the procollagen C-proteinase that
      processes the major fibrillar collagen types I-III, and it may process prolysyl
      oxidase to the mature enzyme necessary to the formation of covalent cross-links
      in collagen and elastic fibers. Type V collagen is a fibrillar collagen of low
      abundance that is incorporated into and helps regulate the shape and diameter of
      type I collagen fibrils. Here we show that, in contrast to its action on
      procollagens I-III, BMP-1 does not cleave the C-propeptide of pro-alpha1(V)
      homotrimers. Instead, the single BMP-1-specific cleavage site within pro
      alpha1(V) chains, lies within the large globular N-propeptide. This cleavage site
      is immediately upstream of a glutamine, thus redefining the specificity of
      cleavage for BMP-1-like enzymes. It also produces an NH2 terminus that
      corresponds to an equivalent NH2 terminus on the processed matrix form of the
      similar alpha1(XI) chain, thus suggesting physiological significance. Cleavage of
      the C-propeptide occurs efficiently in recombinant pro-alpha1(V) homotrimers
      produced in 293-EBNA human embryonic kidney cells, and this cleavage is shown to
      occur immediately downstream of the sequence RTRR. This is similar to sites
      cleaved by subtilisin-like proprotein/prohormone convertases and is shown to be
      specifically cleaved by the recombinant subtilisin-like proprotein/prohormone
      convertase furin.

PMID- 9765283
TI  - SLP-76 is a direct substrate of SHP-1 recruited to killer cell inhibitory
      receptors.
AB  - Activation of immune system cells via antigen-, Fc-, or natural killer cell
      triggering-receptor stimulation is aborted by co-engagement of inhibitory
      receptors. Negative signaling by killer cell inhibitory receptors and related
      receptors depends on the Src homology 2 (SH2)-containing protein tyrosine
      phosphatase SHP-1. Using a combination of direct binding and functional assays,
      we demonstrated that the SH2 domain-containing leukocyte protein 76 (SLP-76) is a
      specific target for dephosphorylation by SHP-1 in T cells and natural killer
      cells. Furthermore, we showed that tyrosine-phosphorylated SLP-76 is required for
      optimal activation of cytotoxic lymphocytes, suggesting that the targeted
      dephosphorylation of SLP-76 by SHP-1 is an important mechanism for the negative
      regulation of immune cell activation by inhibitory receptors.

PMID- 9765284
TI  - A vaccinia virus late transcription factor with biochemical and molecular
      identity to a human cellular protein.
AB  - A factor designated VLTF-X is required to support vaccinia virus late
      transcription in vitro. It has been found that a late promoter DNA binding
      activity cochromatographs and cosediments with VLTF-X activity. Current
      experiments show that VLTF-X activity is present in a variety of uninfected
      mammalian cell types and is indistinguishable from that recovered from infected
      cells based upon several criteria. VLTF-X activity from both sources displays the
      same purification profile over phosphocellulose and DNA affinity resins and has
      the same sedimentation coefficient. In addition, the factors purified from both
      infected and uninfected cells form protein-DNA complexes of identical
      electrophoretic mobility in the presence of vaccinia virus late promoter
      containing DNA. The affinity of these factors for the late promoter probes is
      identical and late promoter-specific based on competition experiments. Moreover,
      VLTF-X purified from both sources bound to late promoter-containing DNA in the
      presence or absence of MgCl2 and ATP and formed complexes resistant to heat
      inactivation. These experiments offer proof that vaccinia virus factor VLTF-X is
      a host cell protein that supports transcription of the viral late genes.

PMID- 9765285
TI  - DNA binding and transactivation characteristics of the mosquito ecdysone receptor
      Ultraspiracle complex.
AB  - The steroid hormone 20-hydroxyecdysone is a key regulatory factor, controlling
      blood-meal triggered egg maturation in mosquitoes. To elucidate the ecdysone
      hierarchy governing this event, we cloned and characterized the ecdysone receptor
      (AaEcR) and the nuclear receptor Ultraspiracle (AaUSP), a retinoid X receptor
      homologue, from the mosquito, Aedes aegypti, which form a functional complex
      capable of ligand and DNA binding. Here we analyzed the DNA-binding properties of
      the AaEcR.AaUSP heterodimer with respect to the effects of nucleotide sequence,
      orientation, and spacing between half-sites in natural Drosophila and synthetic
      ecdysone response element (EcREs). By using an electrophoretic gel mobility shift
      assay, we showed that AaEcR.AaUSP exhibits a broad binding specificity, forming
      complexes with inverted (IR) and direct (DR) repeats of the nuclear receptor
      response element half-site consensus sequence AGGTCA separated by spacers of
      variable length. A single nucleotide spacer was optimal for both imperfect (IRhsp
      1) and perfect (IRper-1) inverted repeats; adding or removing 1 base pair in an
      IRhsp-1 spacer practically abolished binding. However, changing the half-site to
      the consensus sequence AGGTCA (IRper-1) increased binding of AaEcR.AaUSP 10-fold
      over IRhsp-1 and, at the same time, reduced the stringency of the spacer length
      requirement, with IRper-0 to IRper-5 showing detectable binding. Spacer length
      was less important in DRs of AGGTCA (DR-0 to DR-5); although 4 bp was optimal, DR
      3 and DR-5 bound AaEcR.AaUSP almost as efficiently as DR-4. Furthermore, AaEcR.
      AaUSP also bound DRs separated by 11-13 nucleotide spacers. Competition
      experiments and direct estimation of binding affinity (Kd) indicated that, given
      identical consensus half-sites and an optimal spacer, the AaEcR.AaUSP heterodimer
      bound an IR with higher affinity than a DR. Co-transfection assays utilizing CV-1
      cells demonstrated that the mosquito EcR.USP heterodimer is capable of
      transactivating reporter constructs containing either IR-1 or DR-4. The levels of
      transactivation are correlated with the respective binding affinities of the
      response elements (IRper-1 > DR-4 > IRhsp-1). Taken together, these analyses
      predict broad variability in the EcREs of mosquito ecdysone-responsive genes.

PMID- 9765286
TI  - Role of GHF-1 in the regulation of the rat growth hormone gene promoter by
      thyroid hormone and retinoic acid receptors.
AB  - In non-pituitary HeLa cells the unliganded thyroid hormone or retinoic acid
      receptors cause a strong activation of the rat growth hormone promoter that is
      repressed by their ligands. In contrast, after expression of the pituitary
      specific transcription factor GHF-1, thyroid hormone and retinoic acid produce a
      stimulation similar to that found in pituitary cells. Therefore, GHF-1 changes a
      ligand-dependent inhibition into a ligand-dependent activation. The essential
      role of GHF-1 on the rat growth hormone promoter was also demonstrated with AF-2
      defective T3 receptor mutants that show a normal activation of this promoter in
      the presence of GHF-1. Furthermore, a truncated T3 receptor, which lacks the N
      terminus and the DNA binding domain, was able to stimulate this promoter in the
      presence of GHF-1 and exogenous RXR receptors, suggesting the importance of
      protein to protein interactions in this regulation. This study shows that the
      final transcriptional effect depends not only on the type of regulatory promoter
      response elements but also on the presence of other transcriptional activators,
      in the case of the growth hormone promoter, the tissue-specific transcription
      factor GHF-1, which plays a coactivator-like role in this promoter.

PMID- 9765288
TI  - Secondary structure composition and pH-dependent conformational changes of
      soluble recombinant HLA-DM.
AB  - HLA-DM catalyzes the release of invariant chain fragments from newly synthesized
      major histocompatibility complex (MHC) class II molecules, stabilizes empty class
      II molecules, and edits class II-associated peptides by preferentially releasing
      those that are loosely bound. The ability of HLA-DM to carry out these functions
      in vitro is pH dependent, with an optimum at pH 4.5-5.5 and poor activity at pH
      7. The structural basis for these properties of HLA-DM is unknown. Sequence
      homology suggests that HLA-DM resembles classical, peptide-binding MHC class II
      molecules. In this study, we examined whether HLA-DM has a secondary structure
      composition consistent with an MHC fold and whether HLA-DM changes conformation
      between pH 5 and pH 7. Far-UV circular dichroism (CD) spectra of recombinant
      soluble HLA-DM (sDM) indicate that HLA-DM belongs to the alpha/beta class of
      proteins and structurally resembles both MHC class I and class II molecules. The
      CD peak around 198 nm increases upon going from neutral to endosomal pH and drops
      sharply upon denaturation below pH 3.5, distinguishing at least three states of
      sDM: the denatured state and two highly similar folded states. Fluorescence
      emission spectra show a slight blue-shift and a approximately 20% drop in
      intensity at pH 5 compared with pH 7. Unfolding experiments using guanidinium
      chloride show that the stability of sDM is somewhat reduced but not lost at pH 5.
      These results indicate that sDM undergoes a pH-dependent conformational change
      between neutral and endosomal pH. The change seems to involve both hydrogen
      bonding patterns and the hydrophobic core of sDM and may contribute to the pH
      dependence of DM activity.

PMID- 9765287
TI  - Herpesvirus entry mediator ligand (HVEM-L), a novel ligand for HVEM/TR2,
      stimulates proliferation of T cells and inhibits HT29 cell growth.
AB  - Herpesvirus entry mediator (HVEM), a member of the tumor necrosis factor (TNF)
      receptor family, mediates herpesvirus entry into cells during infection. Upon
      overexpression, HVEM activates NF-kappaB and AP-1 through a TNF receptor
      associated factor (TRAF)-mediated mechanism. Using an HVEM-Fc fusion protein, we
      screened soluble forms of novel TNF-related proteins derived from an expressed
      sequence tag data base. One of these, which we designated HVEM-L, specifically
      bound to HVEM-Fc with an affinity of 44 nM. This association was confirmed with
      soluble and membrane forms of both receptor and ligand. HVEM-L mRNA is expressed
      in spleen, lymph nodes, macrophages, and T cells and encodes a 240-amino acid
      protein. A soluble, secreted form of the protein stimulates proliferation of T
      lymphocytes during allogeneic responses, inhibits HT-29 cell growth, and weakly
      stimulates NF-kappaB-dependent transcription.

PMID- 9765289
TI  - Aquaporins in Saccharomyces. Genetic and functional distinctions between
      laboratory and wild-type strains.
AB  - Aquaporin water channel proteins mediate the transport of water across cell
      membranes in numerous species. The Saccharomyces genome data base contains an
      open reading frame (here designated AQY1) that encodes a protein with strong
      homology to aquaporins. AQY1 from laboratory and wild-type strains of
      Saccharomyces were expressed in Xenopus oocytes to determine the coefficients of
      osmotic water permeability (Pf). Oocytes injected with wild-type AQY1 cRNAs
      exhibit high Pf values, whereas oocytes injected with AQY1 cRNAs from laboratory
      strains exhibit low Pf values and have reduced levels of Aqy1p due to two amino
      acid substitutions. When the AQY1 gene was deleted from a wild-type yeast and
      cells were cultured in vitro with cycled hypo-osmolar or hyper-osmolar stresses,
      the AQY1 null yeast showed significantly improved viability when compared with
      the parental wild-type strain. We conclude that Saccharomyces cerevisiae contains
      at least one aquaporin gene, but it is not functional in laboratory strains due
      to apparent negative selection pressures resulting from in vitro methods.

PMID- 9765290
TI  - Characterization of the ATP- and GTP-specific succinyl-CoA synthetases in pigeon.
      The enzymes incorporate the same alpha-subunit.
AB  - Two succinyl-CoA synthetases, one highly specific for GTP/GDP and the other for
      ATP/ADP, have been purified to homogeneity from pigeon liver and breast muscle.
      The two enzymes are differentially distributed in pigeon, with only the GTP
      specific enzyme detected in liver and the ATP-specific enzyme in breast muscle.
      Based on assays in the direction of CoA formation, the ratios of GTP-specific to
      ATP-specific activities in kidney, brain, and heart are approximately 7, 1, and
      0.1, respectively. Both enzymes have the characteristic alpha- and beta-subunits
      found in other succinyl-CoA synthetases. Studies of the alpha-subunit by
      electrophoresis, mass spectrometry, reversed-phase high performance liquid
      chromatography, and peptide mapping showed that it was the same in the two
      enzymes. Characterization of the beta-subunits by the same methods indicated that
      they were different, with the tryptic peptide maps providing evidence that the
      beta-subunits likely differ along their entire sequences. Because the two
      succinyl-CoA synthetases incorporate the same alpha-subunit, the determinants of
      nucleotide specificity must reside within the beta-subunit. Determination of the
      apparent Michaelis constants showed that the affinity of the GTP-specific enzyme
      for GDP is greater than that of the ATP-specific enzyme for ADP (7 versus 250
      microM). Rather large differences in apparent Km values were also observed for
      succinate and phosphate.

PMID- 9765291
TI  - Genetic evidence for the expression of ATP- and GTP-specific succinyl-CoA
      synthetases in multicellular eucaryotes.
AB  - Highly ATP- and GTP-specific isoforms of succinyl-CoA synthetase in pigeon
      incorporate the same alpha-subunit, but different beta-subunits (Johnson, J. D.,
      Muhonen, W. W., and Lambeth, D. O. (1998) J. Biol. Chem. 273, 27573-27579). The
      sequences of the mature subunits were determined by methods based on reverse
      transcription-polymerase chain reaction. The 306-residue mature alpha-subunit in
      pigeon shows >88% identity to its homologues in pig and rat. The sequences of the
      mature ATP- and GTP-specific beta-subunits (A-beta and G-beta, respectively) in
      pigeon are 54% identical. These sequences were used to identify expressed
      sequence tags for human and mouse that were highly homologous to G-beta and A
      beta, respectively. The sequences for mature A-beta and G-beta in mouse and human
      were completed and verified by polymerase chain reaction. The sequence of A-beta
      in pig was also obtained. The mammalian A-beta sequences show >89% identity to
      each other; the G-beta sequences are similarly related. However, pairwise
      comparisons of the A-beta and G-beta sequences revealed <53% identity. Alignment
      with two sequences of the beta-subunit in Caenorhabditis elegans suggests that
      the A-beta and G-beta genes arose by duplication early in the evolution of
      multicellular eucaryotes. The expression of A-beta is strong in numerous mouse
      and human tissues, which suggests that ATP-specific succinyl-CoA synthetase also
      plays an important role in species throughout the animal kingdom.

PMID- 9765292
TI  - The Bloom's syndrome helicase unwinds G4 DNA.
AB  - BLM, the gene that is defective in Bloom's syndrome, encodes a protein homologous
      to RecQ subfamily helicases that functions as a 3'-5' DNA helicase in vitro. We
      now report that the BLM helicase can unwind G4 DNA. The BLM G4 DNA unwinding
      activity is ATP-dependent and requires a short 3' region of single-stranded DNA.
      Strikingly, G4 DNA is a preferred substrate of the BLM helicase, as measured both
      by efficiency of unwinding and by competition. These results suggest that G4 DNA
      may be a natural substrate of BLM in vivo and that the failure to unwind G4 DNA
      may cause the genomic instability and increased frequency of sister chromatid
      exchange characteristic of Bloom's syndrome.

PMID- 9765293
TI  - FCP1, the RAP74-interacting subunit of a human protein phosphatase that
      dephosphorylates the carboxyl-terminal domain of RNA polymerase IIO.
AB  - TFIIF (RAP30/74) is a general initiation factor that also increases the rate of
      elongation by RNA polymerase II. A two-hybrid screen for RAP74-interacting
      proteins produced cDNAs encoding FCP1a, a novel, ubiquitously expressed human
      protein that interacts with the carboxyl-terminal evolutionarily conserved domain
      of RAP74. Related cDNAs encoding FCP1b lack a carboxyl-terminal RAP74-binding
      domain of FCP1a. FCP1 is an essential subunit of a RAP74-stimulated phosphatase
      that processively dephosphorylates the carboxyl-terminal domain of the largest
      RNA polymerase II subunit. FCP1 is also a stoichiometric component of a human RNA
      polymerase II holoenzyme complex.

PMID- 9765294
TI  - Dynamics of histone acetylation in Chlamydomonas reinhardtii.
AB  - The dynamic character of core histone post-translational acetylation in the
      unicellular green alga Chlamydomonas reinhardtii was studied by tritiated acetate
      incorporation. Histone H3 is the major target of acetylation, steady state, and
      in pulse and pulse-chase analyses. Acetylation turnover rates were measured by
      tracer labeling under steady-state conditions. Half-lives of 1.5-3 min were found
      for penta- to mono-acetylation of H3, dynamically acetylated to the 30% level.
      Twenty percent of H3 was multi-acetylated, on average with 3. 2 acetyl-lysines,
      all with rapid turnover. Deacetylase inhibitor trichostatin A (TSA) caused
      doubling of average acetylation levels, primarily as penta-acetylated H3, but
      half of H3 was not acetylated at all. The level of histone H4 acetylation was
      only half that of H3 and a major fraction of mono- and di-acetylated forms
      appeared static. The dynamic fraction had an average half-life of 3.5 min with
      higher turnover rates for more highly acetylated H4 forms. TSA, inhibiting less
      effectively deacetylases active on H4, strongly increased multi-acetylated H4
      levels and doubled average acetylation. As for H3, half of histone H4 remained
      unacetylated. Acetylation of histone H2B was low and of H2A was barely
      measurable. Despite turnover with half-lives of approximately 2 min, no increase
      beyond di-acetylation was seen upon TSA treatment.

PMID- 9765295
TI  - Fcgamma receptor-mediated mitogen-activated protein kinase activation in
      monocytes is independent of Ras.
AB  - Receptors for the Fc portion of immunoglobulin molecules (FcR) present on
      leukocyte cell membranes mediate a large number of cellular responses that are
      very important in host defense, including phagocytosis, cell cytotoxicity,
      production and secretion of inflammatory mediators, and modulation of the immune
      response. Cross-linking of FcR with immune complexes leads, first to activation
      of protein-tyrosine kinases. The molecular events that follow and that transduce
      signals from these receptors to the nucleus are still poorly defined. We have
      investigated the signal transduction pathway from Fc receptors that leads to gene
      activation and production of cytokines in monocytes. Cross-linking of FcR, on the
      THP-1 monocytic cell line, by immune complexes resulted in both activation of the
      transcription factor NF-kappaB and interleukin 1 production. These responses were
      completely blocked by tyrosine kinase inhibitors. In contrast, expression of
      dominant negative mutants of Ras and Raf-1, in these cells, did not have any
      effect on FcR-mediated nuclear factor activation, suggesting that the mitogen
      activated protein kinase (MAPK) signaling pathway was not used by these
      receptors. However, MAPK activation was easily detected by in vitro kinase
      assays, after FcR cross-linking with immune complexes. Using the specific
      MAPK/extracellular signal-regulated kinase kinase (MAPK kinase) inhibitor
      PD98059, we found that MAPK activation is necessary for FcR-dependent activation
      of the nuclear factor NF-kappaB. These results strongly suggest that the
      signaling pathway from Fc receptors leading to expression of different genes
      important to leukocyte biology, initiates with tyrosine kinases and requires MAPK
      activation; but in contrast to other tyrosine kinase receptors, FcR-mediated MAPK
      activation does not involve Ras and Raf.

PMID- 9765296
TI  - Brain-derived neurotrophic factor induces rapid and transient release of
      glutamate through the non-exocytotic pathway from cortical neurons.
AB  - There is increasing interest in the involvement of neurotrophins in neural
      transmission and plasticity. Thus, we investigated the effects of brain-derived
      neurotrophic factor (BDNF) on glutamate release from cortical neurons. Treatment
      of cultured cortical neurons with BDNF induced rapid and transient release of
      glutamate. This effect was suggested to be mediated by TrkB activation because
      K252a inhibited the release of glutamate and BDNF phosphorylated TrkB within 30
      s. BDNF-induced glutamate release was observed even when using Ca2+-free assay
      buffer but was inhibited by BAPTA-AM, a cell-permeable Ca2+ chelator. Therefore,
      BDNF-induced glutamate release was independent of extracelluar Ca2+ but dependent
      on intracellular Ca2+. Because normal neurotransmitter release is exocytotic, the
      involvement of the exocytotic pathway in BDNF-induced glutamate release was
      examined. As botulinum toxin is known to cleave exocytosis-associated proteins,
      thereby inhibiting exocytosis, it was applied to neurons prior to the release
      assay. Although botulinum toxin B cleaved VAMP2 and inhibited Ca2+-triggered
      glutamate release, it did not inhibit the BDNF-induced release of glutamate.
      These results strongly suggested that BDNF induces rapid and transient release of
      glutamate from cortical neurons through a non-exocytotic pathway.

PMID- 9765297
TI  - Purification and characterization of UDP-GlcNAc:Galbeta1-4GlcNAcbeta1-3*Galbeta1
      4Glc(NAc)-R(GlcNAc to *Gal) beta1,6N-acetylglucosaminyltransferase from hog small
      intestine.
AB  - A beta1,6N-acetylglucosaminyltransferase (beta1-6GnT) responsible for the
      formation of the beta1,6-branched poly-N-acetyllactosamine structure has been
      purified 210,000-fold in 2.4% yield from a homogenate of hog small intestine by
      successive column chromatographies involving CM-Sepharose FF, Ni2+-chelating
      Sepharose FF, and UDP-hexanolamine-agarose, using an assay wherein
      pyridylaminated lacto-N-neotetraose (Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc-PA) was
      used as an acceptor substrate, and the reaction product was Galbeta1-4GlcNAcbeta1
      3(GlcNAcbeta1-6)Galbeta1-4 Glc-PA. The apparent molecular weight of the purified
      enzyme was 76,000 under nonreducing conditions. The enzyme has a pH optimum at
      7.0 and has no requirement for any divalent metal ions. The Km values for
      pyridylaminated lacto-N-neotetraose and UDP-GlcNAc were 0.96 and 2. 59 mM,
      respectively. For its activity, this enzyme was shown to have an absolute
      requirement of at least a complete LacNAc (LacNAc = Galbeta1-4GlcNAc) residue
      bound to position 3 of the acceptor Gal residues, i.e. it is capable of acting
      only on the Gal residues of internal LacNAc units. The data strongly suggest that
      this enzyme could be involved in generating branches to central positions of
      preformed as well as growing polylactosamine chains, but not in synthesizing the
      distal branches to growing polylactosamine chains.

PMID- 9765298
TI  - The centrally acting beta1,6N-acetylglucosaminyltransferase (GlcNAc to gal).
      Functional expression, purification, and acceptor specificity of a human enzyme
      involved in midchain branching of linear poly-N-acetyllactosamines.
AB  - In the present experiments the cDNA coding for a truncated form of the beta1,6N
      acetylglucosaminyltransferase responsible for the conversion of linear to
      branched polylactosamines in human PA1 cells was expressed in Sf9 insect cells.
      The catalytic ectodomain of the enzyme was fused to glutathione S-transferase,
      allowing effective one-step purification of the glycosylated 67-74-kDa fusion
      protein. Typically a yield of 750 microg of the purified protein/liter of
      suspension culture was obtained. The purified recombinant protein catalyzed the
      transfer of GlcNAc from UDP-GlcNAc to the linear tetrasaccharide Galbeta1
      4GlcNAcbeta1-3Galbeta1-4GlcNAc, converting the acceptor to the branched
      pentasaccharide Galbeta1-4GlcNAcbeta1-3(GlcNAcbeta1-6)Galbeta1-4 GlcNAc as shown
      by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry,
      degradative experiments, and 1H NMR spectroscopy of the product. By contrast, the
      recombinant enzyme did not catalyze any reaction when incubated with UDP-GlcNAc
      and the trisaccharide GlcNAcbeta1-3Galbeta1-4GlcNAc. Accordingly, we call the
      recombinant beta1,6-GlcNAc transferase cIGnT6 to emphasize its action at central
      rather than peridistal galactose residues of linear polylactosamines in the
      biosynthesis of blood group I antigens. Taken together this in vitro expression
      of I-branching enzyme, in combination with the previously cloned enzymes,
      beta1,4galactosyltransferase and beta1, 3N-acetylglucosaminyltransferase, should
      allow the general synthesis of polylactosamines based totally on the use of
      recombinant enzymes.

PMID- 9765299
TI  - Amyloid beta-peptide possesses a transforming growth factor-beta activity.
AB  - Amyloid beta-peptide (Abeta) of 39-42 amino acid residues is a major constituent
      of Alzheimer's disease neurite plaques. Abeta aggregates (fibrils) are believed
      to be responsible for neuronal damage and dysfunction, as well as microglia and
      astrocyte activation in disease lesions by multiple mechanisms. Since Abeta
      aggregates possess the multiple valencies of an FAED motif (20th to 23rd amino
      acid residues), which resembles the putative transforming growth factor-beta (TGF
      beta) active site motif, we hypothesize that Abeta monomers and Abeta aggregates
      may function as TGF-beta antagonists and partial agonists, analogous to
      previously described monovalent and multivalent TGF-beta peptide antagonists and
      agonists (Huang, S. S., Liu, Q., Johnson, F. E., Konish, Y., and Huang, J. S.
      (1997) J. Biol. Chem. 272, 27155-27159). Here, we report that the Abeta monomer,
      Abeta-(1-40) and its fragment, containing the motif inhibit radiolabeled TGF-beta
      binding to cell-surface TGF-beta receptors in mink lung epithelial cells (Mv1Lu
      cells). Abeta-(1-40)-bovine serum albumin conjugate (Abeta-(1-40)-BSA), a
      multivalent synthetic analogue of Abeta aggregates, exhibited cytotoxicity toward
      bovine cerebral endothelial cells and rat post-mitotic differentiated hippocampal
      neuronal cells (H19-7 cells) and inhibitory activities of radiolabeled TGF-beta
      binding to TGF-beta receptors and TGF-beta-induced plasminogen activator
      inhibitor-1 expression, that were approximately 100-670 times more potent than
      those of Abeta-(1-40) monomers. At less than micromolar concentrations, Abeta-(1
      40)-BSA but not Abeta-(1-40) monomers inhibited proliferation of Mv1Lu cells.
      Since TGF-beta is an organizer of responses to neurodegeneration and is also
      found in neurite plaques, the TGF-beta antagonist and partial agonist activities
      of Abeta monomers and aggregates may play an important role in the pathogenesis
      of the disease.

PMID- 9765300
TI  - A transcriptional coactivator, steroid receptor coactivator-3, selectively
      augments steroid receptor transcriptional activity.
AB  - Estrogen receptors ERalpha and ERbeta are members of the family of nuclear
      hormone receptors and act as ligand-inducible transcriptional factors, which
      regulate the expression of target genes on binding to cognate response elements.
      We report here the characterization of steroid receptor coactivator-3 (SRC-3), a
      coactivator of nuclear receptor transcription that is a member of a family of
      steroid receptor coactivators that includes SRC-1 and transcription intermediate
      factor-2. SRC-3 enhanced ERalpha and progesterone receptor-stimulated gene
      transcription in a ligand-dependent manner, but stimulation of ERbeta-mediated
      transcription was not observed. Protein-protein interaction assays, including
      real-time interaction analyses with BIAcore, demonstrated that the affinity of
      the ERalpha interaction with SRC-3 was much higher than that observed for the
      ERbeta interaction with SRC-3. Mutational analysis suggests a potential interplay
      between the transactivation function-1 and -2 domains of ERalpha and SRC-3.
      Furthermore, an intrinsic transactivation function was observed in the C-terminal
      half of SRC-3. Finally, SRC-3 was differentially expressed in various tissues
      and, among several tumor cells examined, was most abundant in the nuclear
      fraction of MCF-7 breast cancer cells. Therefore, SRC-3, a third member of a
      family of steroid receptor coactivators, has a distinct tissue distribution and
      intriguing selectivity between ERalpha and ERbeta.

PMID- 9765301
TI  - Differential downstream functions of protein kinase Ceta and -theta in EL4 mouse
      thymoma cells.
AB  - Sensitive EL4 mouse thymoma cells (s-EL4) respond to phorbol esters with growth
      inhibition, adherence to substrate, and production of cytokines including
      interleukin 2. Since these cells express several of the phorbol ester-sensitive
      protein kinase C (PKC) isozymes, the function of each isozyme remains unclear.
      Previous studies demonstrated that s-EL4 cells expressed substantially more
      PKCeta and PKCtheta than did EL4 cells resistant to phorbol esters (r-EL4). To
      examine potential roles for PKCeta and PKCtheta in EL4 cells, wild type and
      constitutively active versions of the isozymes were transiently expressed using a
      Sindbis virus system. Expression of constitutively active PKCeta, but not
      PKCtheta, in s- and r-EL4 cells altered cell morphology and cytoskeletal
      structure in a manner similar to that of phorbol ester treatment, suggesting a
      role for PKCeta in cytoskeletal organization. Prolonged treatment of s-EL4 cells
      with phorbol esters results in inhibition of cell cycling along with a decreased
      expression of most of the PKC isozymes, including PKCtheta. Introduction of
      virally expressed PKCtheta, but not PKCeta, overcame the inhibitory effects of
      the prolonged phorbol ester treatment on cell cycle progression, suggesting a
      possible involvement of PKCtheta in cell cycle regulation. These results support
      differential functions for PKCeta and PKCtheta in T cell activation.

PMID- 9765302
TI  - Identification of in vivo phosphorylation sites required for protein kinase D
      activation.
AB  - Protein kinase D (PKD) is activated by phosphorylation in intact cells stimulated
      by phorbol esters, cell permeant diacylglycerols, bryostatin, neuropeptides, and
      growth factors, but the critical activating residues in PKD have not been
      identified. Here, we show that substitution of Ser744 and Ser748 with alanine
      (PKD-S744A/S748A) completely blocked PKD activation induced by phorbol-12,13
      dibutyrate (PDB) treatment of intact cells as assessed by autophosphorylation and
      exogenous syntide-2 peptide substrate phosphorylation assays. Conversely,
      replacement of both serine residues with glutamic acid (PKD-S744E/S748E) markedly
      increased basal activity (7.5-fold increase compared with wild type PKD). PKD
      S744E/S748E mutant was only slightly further stimulated by PDB treatment in vivo,
      suggesting that phosphorylation of these two sites induces maximal PKD
      activation. Two-dimensional tryptic phosphopeptide analysis obtained from PKD
      mutants immunoprecipitated from 32P-labeled transfected COS-7 cells showed that
      two major spots present in the PDB-stimulated wild type PKD or the kinase-dead
      PKD-D733A phosphopeptide maps completely disappeared in the kinase-deficient
      triple mutant PKD-D733A/S744E/S748E. Our results indicate that PKD is activated
      by phosphorylation of residues Ser744 and Ser748 and thus provide the first
      example of a non-RD kinase that is up-regulated by phosphorylation of
      serine/threonine residues within the activation loop.

PMID- 9765303
TI  - The mechanism of inhibition of topoisomerase IV by quinolone antibacterials.
AB  - Topoisomerase IV (Topo IV) is a mediator of quinolone toxicity in bacteria. In
      this work, we demonstrate that norfloxacin, a model quinolone, converts
      Escherichia coli Topo IV into a poisonous adduct on DNA as opposed to inhibiting
      topoisomerase activity. Norfloxacin inhibition of Topo IV induces a slow decline
      in DNA synthesis that parallels cell death. Treatment of cells with a lethal
      concentration of the antibacterial did not block chromosome segregation, the
      phenotype of catalytic inhibition of Topo IV. Instead, norfloxacin causes DNA
      damage, as evidenced by the induction of the SOS pathway for DNA repair; the
      increase in susceptibility to the drug by mutations in genes for DNA repair
      pathways including recA, recB, and uvrD; and the efficient detergent-induced
      linearization of plasmid DNA in drug-treated cells. Wild-type and drug-resistant
      alleles of Topo IV are co-dominant, but we find that mutations in recA, seqA, or
      gyrB result in unconditional dominance of the sensitive allele, the
      characteristic of a poisoning mode of inhibition. These mutations either
      compromise chromosome integrity or force Topo IV to play a more active role in
      DNA unlinking in front of the replication fork. We interpret our results in terms
      of distinct but complementary roles of Topo IV and gyrase in DNA replication.

PMID- 9765304
TI  - Transcriptional regulation of mouse mu-opioid receptor gene.
AB  - Previously, the existence of dual promoters was reported in mouse mu-opioid
      receptor (mor) gene, with mor transcription in the mouse brain predominantly
      initiated by the proximal promoter. In this study, we further analyzed the
      proximal promoter region, base pairs -450 to -249, to identify cis-DNA regulatory
      elements and trans-acting protein factors that are important for mor promoter
      activity. The results revealed that a mor inverted GA (iGA) motif and a canonical
      Sp1 binding site are required for the promoter activity. Using electrophoretic
      mobility shift analysis, we identified nuclear proteins that specifically bind to
      the mor iGA motif and that are immunologically related to Sp1 and Sp3. Mutation
      of the mor iGA motif, resulting in a loss of Sp binding, led to a 50% decrease in
      activity. Mutation of the canonical Sp1 binding site yielded a lesser
      (approximately 25%) loss of activity. Mutation of both motifs together resulted
      in an approximately 70% decrease in activity. In cotransfection assays using
      Drosophila SL2 cells, Sp1 trans-activated the promoter in a manner dependent on
      the presence of mor iGA and canonical Sp1 binding motifs. Sp3 can also trans
      activate the promoter, and furthermore, Sp1 and Sp3 can trans-activate the mor
      promoter additively. Our results suggest that combined or cooperative interaction
      of Sp transcription factors within the proximal promoter is necessary for
      activation of mor gene transcription.

PMID- 9765305
TI  - Transcriptional regulation of cyclooxygenase-2 in mouse skin carcinoma cells.
      Regulatory role of CCAAT/enhancer-binding proteins in the differential expression
      of cyclooxygenase-2 in normal and neoplastic tissues.
AB  - Many studies have suggested that overexpression of cyclooxygenase-2 (COX-2)
      contributes to the development of tumors in several tissues. COX-2 expression
      tends to be up-regulated in various types of tumors and transformed cell lines,
      and the overexpression of COX-2 is caused by enhanced transcription of the gene.
      In an attempt to characterize the signaling pathway leading to the overexpression
      of COX-2 in the mouse skin carcinoma cell line JWF2, we investigated cis- and
      trans-acting factors required for COX-2 expression and demonstrated a molecular
      mechanism by which COX-2 is expressed differentially in normal and neoplastic
      tissues. Two regions of the COX-2 promoter containing an E-box and nuclear factor
      IL6 site were identified as the positive regulatory elements through transient
      transfections with luciferase reporter vectors containing the various 5'-flanking
      regions of the promoter. Moreover, electrophoretic mobility shift assays and
      cotransfection experiments showed that upstream stimulatory factors and
      CCAAT/enhancer-binding proteins (C/EBPs) bind to the E-box and nuclear factor IL6
      site, respectively, and functionally transactivate the COX-2 promoter. We also
      found that C/EBP isoforms are expressed differentially during mouse skin
      carcinogenesis, suggesting that overexpression of COX-2 in tumors may be caused
      by a change in C/EBP expression levels.

PMID- 9765307
TI  - Regulation of adenylyl cyclase by membrane potential.
AB  - Mammalian adenylyl cyclases possess 12 transmembrane-spanning domains and bear a
      superficial resemblance to certain classes of ion channels. Some evidence
      suggests that bacterial and sea urchin sperm adenylyl cyclases can be regulated
      by membrane depolarization. In the present study, we explored the effect of
      altering membrane potential on the adenylyl cyclase activity of cerebellar
      granule cells with acute potassium depolarization. A biphasic stimulatory and
      then inhibitory response is evoked by progressive increases in the extracellular
      [K]:[Na] ratio in the absence of extracellular Ca2+. This effect does not mimic
      the linear increase in membrane potential elicited under the same conditions.
      Instead it appears as though membrane depolarization opens L-type (nimodipine
      sensitive) Ca2+ channels, allowing the entry of Na+, which directly stimulates
      adenylyl cyclase activity. Gramicidin, which generates pores that are permeable
      to monovalent cations, and concurrently eliminates the membrane potential,
      permits a similar stimulation by extracellularly applied Na+. Although the
      results indicate no direct sensitivity of cerebellar granule cell adenylyl
      cyclase to membrane potential, they do demonstrate that, as a result of membrane
      depolarization, the influx of Na+, as well as Ca2+, will elevate cAMP levels.

PMID- 9765306
TI  - Components of the SMRT corepressor complex exhibit distinctive interactions with
      the POZ domain oncoproteins PLZF, PLZF-RARalpha, and BCL-6.
AB  - Many transcription factors function by repressing gene transcription. For a
      variety of these transcription factors the ability to physically recruit
      auxiliary proteins, denoted corepressors, is crucial for the ability to silence
      gene expression. We and others have previously implicated the SMRT corepressor in
      the actions of the PLZF transcription factor and in the function of its oncogenic
      derivative, PLZF-retinoic acid receptor (RARalpha), in promyelocytic leukemia. We
      report here that PLZF, and a structurally similar transcriptional repressor, BCL
      6, can interact with a variety of corepressor proteins in addition to SMRT,
      including the mSin3A protein and (for PLZF) histone deacetylase-1. Unexpectedly,
      these additional interactions with corepressor components are nonequivalent for
      these otherwise similar oncoproteins, suggesting that transcriptional repression
      by BCL-6 and by PLZF may differ in mechanism. Furthermore, we demonstrate that
      the oncogenic PLZF-RARalpha chimera lacks several important corepressor
      interaction sites that are present in the native PLZF protein. Thus the t(11;17)
      translocation that creates the PLZF-RARalpha chimera generates an oncoprotein
      with potentially novel regulatory properties distinct from those of either
      parental protein. Our results demonstrate that otherwise similar transcription
      factors can differ notably in their interactions with the corepressor machinery.

PMID- 9765308
TI  - A novel transcription initiation factor (TIF), TIF-IE, is required for
      homogeneous Acanthamoeba castellanii TIF-IB (SL1) to form a committed complex.
AB  - The fundamental transcription initiation factor (TIF) for ribosomal RNA
      expression by eukaryotic RNA polymerase I, TIF-IB, has been purified to near
      homogeneity from Acanthamoeba castellanii using standard techniques. The purified
      factor consists of the TATA-binding protein and four TATA-binding protein
      associated factors with relative molecular weights of 145,000, 99,000, 96,000,
      and 91,000. This yields a calculated native molecular weight of 460, 000, which
      compares well with its mass determined by scanning transmission electron
      microscopy (493,000) and its sedimentation rate, which is close to RNA polymerase
      I (515,000). Both impure and nearly homogeneous TIF-IB exhibit an apparent
      equilibrium dissociation constant of 56 +/- 3 pM. However, although impure TIF-IB
      can form a promoter-DNA complex resistant to challenge by other promoter
      containing DNAs, near homogeneous TIF-IB cannot do so. An additional
      transcription factor, dubbed TIF-IE, restores the ability of near homogeneous TIF
      IB to sequester DNA into a committed complex.

PMID- 9765309
TI  - Inhibitor-1 interaction domain that mediates the inhibition of protein
      phosphatase-1.
AB  - Inhibitor-1 (I-1), a cyclic AMP-regulated phosphoprotein, inhibits protein
      phosphatase-1 (PP1) activity in response to hormones. The molecular mechanism for
      PP1 inhibition by I-1 remains unknown. Mutation of nine acidic residues lining a
      proposed I-1-binding channel in rabbit PP1alpha yielded one mutant (E256A)
      slightly impaired in its inhibition by I-1, with the IC50 increased by 3-fold,
      and one mutant (E275R) located in the beta12-beta13 loop that showed 4-fold
      enhanced inhibition by I-1. Substituting Tyr-272, a proposed binding site for the
      toxins okadaic acid and microcystin-LR, in the beta12-beta13 loop with Trp, Phe,
      Asp, Arg, or Ala impaired PP1alpha inhibition by I-1 by 8-10-fold. Chemical
      mutagenesis of the Saccharomyces cerevisiae PP1 gene (GLC7) yielded 20 point
      mutations in the PP1 coding region. Two-hybrid analyses and biochemical assays of
      these yeast enzymes identified four additional residues in the beta12-beta13 loop
      that were required for PP1 binding and inhibition by I-1. Ten-fold higher
      concentrations of I-1 were required to inhibit these mutants. Finally, deletion
      of the beta12-beta13 loop from PP1alpha maintained full enzyme activity, but
      attenuated inhibition by I-1 by >100-fold. These data identified the beta12
      beta13 loop in the PP1 catalytic subunit as a domain that mediates binding and
      enzyme inhibition by I-1.

PMID- 9765310
TI  - The pleckstrin homology domains of dynamin isoforms require oligomerization for
      high affinity phosphoinositide binding.
AB  - The dynamins are 100-kDa GTPases involved in the scission event required for
      formation of endocytotic vesicles. The two main described mammalian dynamins
      (dynamin-1 and dynamin-2) both contain a pleckstrin homology (PH) domain, which
      has been implicated in dynamin binding to (and activation by) acidic
      phospholipids, most notably phosphoinositides. We demonstrate that the PH domains
      of both dynamin isoforms require oligomerization for high affinity
      phosphoinositide binding. Strong phosphoinositide binding was detected only when
      the PH domains were dimerized by fusion to glutathione S-transferase, or via a
      single engineered intermolecular disulfide bond. Phosphoinositide binding
      specificities agreed reasonably with reported effects of different phospholipids
      on dynamin GTPase activity. Although they differ in their ability to inhibit
      rapid endocytosis in adrenal chromaffin cells, the dynamin-1 and dynamin-2 PH
      domains showed identical phosphoinositide binding specificities. Since
      oligomerization is required for binding of the dynamin PH domain to
      phosphoinositides, it follows that PH domain-mediated phosphoinositide binding
      will favor oligomerization of intact dynamin (which has an inherent tendency to
      self-associate). We propose that the dynamin PH domain thus mediates the observed
      cooperative binding of dynamin to membranes containing acidic phospholipids and
      promotes the self-assembly that is critical for both stimulation of its GTPase
      activity and its ability to achieve membrane scission.

PMID- 9765311
TI  - Protein kinase C-dependent in vivo phosphorylation of prourokinase leads to the
      formation of a receptor competitive antagonist.
AB  - We recently reported that in vivo phosphorylation of urokinase-type plasminogen
      activator on Ser138/303 prevents its catalytic-independent ability to promote
      myelomonocytic cell adherence and motility. We now show that Ca2+ activated,
      phospholipid-dependent protein kinase C from rat brain phosphorylates in vitro a
      peptide corresponding to prourokinase residues 133-143 (DGKKPSSPPEE) and the full
      length molecule on Ser138/139. The in vivo involvement of the protein kinase C
      isoenzyme family is supported by the finding that inhibition of kinase C activity
      prevents prourokinase phosphorylation on Ser138/303 in A431 human carcinoma
      cells. Conversely, a short treatment of A431 cells with phorbol myristate acetate
      increases the extent of phosphorylated prourokinase and, concomitantly, affects
      its function; under these conditions, the capability of prourokinase to up
      regulate U937 monocyte-like cell adherence is severely impaired, although
      receptor binding is unaltered. By the aid of a "phosphorylation-like" variant
      (Ser138 to Glu) we show that modification of Ser138 is sufficient to confer to
      prourokinase the antagonistic properties observed following in vivo stimulation
      of protein kinase C activity. These observations provide the first evidence that
      protein kinase C directs the formation of a receptor competitive antagonist by
      regulating the in vivo phosphorylation state of prourokinase.

PMID- 9765312
TI  - MEBA derepresses the proximal myelin basic protein promoter in oligodendrocytes.
AB  - The central nervous system expression of myelin basic protein (MBP) is restricted
      to oligodendrocytes and is developmentally regulated; these regulatory features
      are transcriptionally mediated. We have previously shown that the proximal 149
      nucleotides of the MBP promoter were both necessary and sufficient to activate
      the transcription of MBP in cultured oligodendrocytes, but not in other cell
      types. Sequences within the distal portion of this promoter, which contains a
      nuclear factor 1 (NF1) binding site, repressed activation of the MBP promoter in
      Cos-7 cells, but not in oligodendrocytes. We now describe a sequence upstream of
      and partially overlapping the NF1 site that activates the MBP promoter in
      oligodendrocytes, but not in Cos-7 cells. A protein complex binds to this site,
      designated MEBA (myelinating glia-enriched DNA binding activity), and is enriched
      in nuclear extracts prepared from the brain, oligodendrocytes, and Schwann cells.
      The amount of MEBA parallels MBP expression and myelinogenesis in the developing
      brain and parallels new MBP expression as purified oligodendrocytes
      differentiate. Mutational analyses of binding and function distinguish MEBA, an
      activator, from NF1, a repressor of MBP transcription, and suggest that MEBA
      consists of at least two proteins. Because the binding sites of MEBA and NF1
      overlap, we suggest that MEBA may either compete with or modify NF1 binding,
      thereby activating the MBP promoter in oligodendrocytes.

PMID- 9765313
TI  - Cloning and expression of a novel, tissue specifically expressed member of the
      UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase family.
AB  - We report the cloning and expression of the fifth member of the mammalian UDP
      GalNAc:polypeptide N-acetylgalactosaminyltransferase (ppGaNTase) family.
      Degenerate polymerase chain reaction amplification and hybridization screening of
      a rat sublingual gland (RSLG) cDNA library were used to identify a novel isoform
      termed ppGaNTase-T5. Conceptual translation of the cDNA reveals a uniquely long
      stem region not observed for other members of this enzyme family. Recombinant
      proteins expressed transiently in COS7 cells displayed transferase activity in
      vitro. Relative activity and substrate preferences of ppGaNTase-T5 were compared
      with previously identified isoforms (ppGaNTase-T1, -T3, and -T4); ppGaNTase-T5
      and -T4 glycosylated a restricted subset of peptides whereas ppGaNTase-T1 and -T3
      glycosylated a broader range of substrates. Northern blot analysis revealed that
      ppGaNTase-T5 is expressed in a highly tissue-specific manner; abundant expression
      was seen in the RSLG, with lesser amounts of message in the stomach, small
      intestine, and colon. Therefore, the pattern of expression of ppGaNTase-T5 is the
      most restricted of all isoforms examined thus far. The identification of this
      novel isoform underscores the diversity and complexity of the family of genes
      controlling O-linked glycosylation.

PMID- 9765314
TI  - LY353381.HCl: a novel raloxifene analog with improved SERM potency and efficacy
      in vivo.
AB  - Body weight, uteri, serum cholesterol and bones were shown previously in vivo to
      be sensitive to circulating levels of estrogen, as well as to synthetic,
      nonsteroidal ligands termed selective estrogen receptor modulators (SERM). In
      this study, we examined the in vivo effects of a new potent SERM on these tissues
      in 6-month-old, ovariectomized rats that were orally dosed with 0.0001-10
      mg/kg/day LY353381.HCl for 5 weeks. LY353381.HCl prevented the ovariectomy
      induced increase in body weight and serum cholesterol levels of treated rats and
      lowered them to below sham levels in a dose dependent manner, with maximum
      efficacy similar to estrogen or raloxifene. However, LY353381.HCl was
      consistently more potent than raloxifene, with a half maximal efficacious dose of
      0.001 mg/kg for the reduction of body weight and cholesterol. In the uterus,
      LY353381.HCl had marginal effects on uterine weight compared to ovariectomized
      controls (OVX) like raloxifene, but unlike estrogen. Histological examination of
      uterine epithelial cell height showed little to no stimulatory effect of
      LY353381.HCl on the endometrium. Quantitative computed tomographic analyses
      (pQCT) of tibiae showed that LY353381.HCl prevented loss of bone due to
      ovariectomy with an ED50 of about 0.01 mg/kg with maximal efficacy observed at
      0.1-1 mg/kg/day. Maximally attainable bone mineral density and content with
      LY353381.HCl were not significantly different from Sham or ovariectomized rats
      treated with estrogen or raloxifene. Interestingly, assessment of bone quality by
      biomechanical analyses showed that LY353381.HCl preserved the strength of the
      femora neck and midshaft, while improving the Young's modulus of cortical bone to
      beyond estrogen, raloxifene or sham levels. In uteri of immature rats treated
      with estrogen, LY353381.HCl antagonized the estrogen-induced elevation in uterine
      weight down to vehicle-dosed control levels with ED50 of 0.03 mg/kg/day.
      Therefore, LY353381.HCl was 30-100 times more potent than raloxifene in
      preventing ovariectomy effects on body weight, serum cholesterol and bone, while
      maintaining estrogen antagonist effects on the uterus. These animal data suggest
      that LY353381.HCl may have advantages over estrogen or raloxifene in the
      prevention of bone loss and treatment of other tissues in postmenopausal women.

PMID- 9765315
TI  - DMPS (2,3-dimercaptopropane-1-sulfonate, dimaval) decreases the body burden of
      mercury in humans exposed to mercurous chloride.
AB  - DMPS (2,3-dimercaptopropane-1-sulfonate, Na salt), when used as a challenge test
      for mercury in workers involved in the production of a calomel skin-bleaching
      lotion and in direct contact with mercurous chloride, elevated urine levels of
      mercury. A DMPS treatment regimen was devised and initiated. Three days after the
      challenge test, DMPS was administered p.o. (400 mg per day) for 8 days, followed
      by a no-treatment period of five days. A new cycle of DMPS treatment for 7 days
      was initiated and followed by 5 days without treatment. A third period of
      treatment was begun for 6 days, followed by a 5-day no-treatment period. The
      urinary mercury greatly increased during those periods when DMPS was administered
      (1754, 314, and 173 microgram/24 h for the periods 1, 2 and 3, compared with 106,
      48 and 53 microgram/24 h on the corresponding no-treatment periods). One of the
      workers presented signs of drug intolerance and was discharged after receiving
      the first cycle of treatment. DMPS treatment was effective in lowering the body
      burden of mercury and in decreasing the urinary mercury concentration to normal
      levels.

PMID- 9765317
TI  - Metabolic and cardiovascular effects of the adenosine A1 receptor agonist N6-(p
      sulfophenyl)adenosine in diabetic Zucker rats: influence of the disease on the
      selectivity of action.
AB  - Studies were designed to investigate differences in pharmacokinetics and
      pharmacodynamics of the adenosine A1 receptor agonist N6-(p-sulfophenyl)adenosine
      (SPA) between lean and obese Zucker rats. In conscious rats, time courses of the
      effect on heart rate and parameters of lipid metabolism (fatty acids, glycerol)
      were monitored in combination with the decline of drug concentrations after i.v.
      administration of 100 microgram SPA in 15 min. Small differences in
      pharmacokinetics of SPA were observed between lean and obese rats. Values for
      clearance and volume of distribution were 1.2 +/- 0.2 ml/min and 88 +/- 10 ml in
      lean, and 1.6 +/- 0.1 ml/min and 110 +/- 7 ml in obese animals, respectively.
      Modelling of the concentration-heart rate relationship on the basis of the
      sigmoidal Emax model revealed no difference in EC50 (99 +/- 12 and 118 +/- 17
      ng/ml) or Emax (-191 +/- 16 and -185 +/- 22 bpm) between the lean and obese rats.
      The metabolic effects of SPA were totally different between lean and obese rats.
      Potent (EC50 = 18 +/- 3 ng/ml) inhibition of lipolysis was observed in the lean
      rats. In obese rats, SPA was less potent (EC50 = 109 +/- 36 ng/ml) resulting in
      short lasting antilipolytic effect. Furthermore, administration of SPA resulted
      in a significant decrease in insulin concentrations. These findings show that
      changes in glucose and lipid metabolism may be associated with an altered
      sensitivity to the antilipolytic actions of adenosine A1 receptor agonists.

PMID- 9765316
TI  - Exposure to ochratoxin A impairs organic anion transport in proximal-tubule
      derived opossum kidney cells.
AB  - Ochratoxin A (OTA) is a widespread mycotoxin, which is nephrotoxic and
      carcinogenic. Because a decline in net-secretion of para-aminohippuric acid (PAH)
      was observed after chronic OTA exposition in vivo, we investigated the effect of
      OTA on proximal-tubule-derived opossum kidney (OK) cells. OTA up to 10(-5)
      mol/liter had no acute effect on PAH transport when bovine serum albumin (BSA)
      was present. By contrast, 72-hr incubation of OK cells led to a decrease of PAH
      transport with half-maximal inhibition at 6 . 10(-7) mol/liter for
      transepithelial secretion and 6 . 10(-8) mol/liter for basolateral uptake of PAH.
      Incubation of OK cells with 10(-6) mol/liter OTA for 72 hr reduced the affinity
      of PAH uptake, and decreased the maximum secretion rate to one-fifth of control
      values. Apical uptake of amino acids and basolateral uptake of glutarate were not
      affected. In addition, no signs of general toxic action could be observed.
      Specific basolateral binding affinity of PAH was reduced to 50% of control.
      Furthermore, incubation with OTA led to a decrease of PAH efflux across the
      apical membrane, although efflux across the basolateral membrane and the amount
      remaining in the cells increased as compared to control. By contrast to control
      cells, uptake of PAH in OTA-treated cells was not stimulated after preloading
      with glutarate. Our data show, that 1) long-term incubation with free OTA in the
      nanomolar range reduces the activity of the organic anion transporter, 2) without
      influencing general cell function. 3) OTA seems to act preferentially on organic
      anion transport, by affecting the exchange of organic anions and dicarboxylates.
      4) Thereby, OTA reduces its own secretion. 5) The excretion of other xenobiotics
      and drugs may be also impaired, whereby OTA can exert an indirect toxic action.

PMID- 9765318
TI  - Excretion of ofloxacin into saliva in rats with renal failure.
AB  - To clarify effects of renal failure on salivary distribution of ofloxacin (OFLX),
      a quinolone antibiotics, blood, parotid and mandibular saliva were collected from
      the single-step 5/6th-nephrectomized and sham-operated (control) rats after bolus
      i. v. administration of OFLX (5 mg/kg). The concentrations of OFLX in these
      samples were determined by high-performance liquid chromatography. Renal failure
      induced by the partial nephrectomy significantly elevated plasma levels and
      cumulative salivary excretion of OFLX when compared to control rats. Total body
      clearance was significantly decreased by the renal failure, although salivary
      clearance of the partially nephrectomized rats was about three times larger than
      that of the control. At the terminal phase, the saliva/plasma concentration
      ratios of OFLX for parotid and mandibular saliva in control rats was 0.249 +/-
      0.180 and 0.136 +/- 0.024, respectively, and there was a significant difference
      between both salivary glands. The saliva/plasma concentration ratios in the rats
      with renal failure were significantly greater than those in the control group in
      both parotid (about 3.2 times) and mandibular (about 2.5 times) saliva. The
      results of this study suggest that the salivary excretion of OFLX is
      significantly increased by renal failure and a glandular difference in the
      salivary excretion of OFLX exists in both rats with normal and impaired renal
      function.

PMID- 9765319
TI  - Transport of temocaprilat into rat hepatocytes: role of organic anion
      transporting polypeptide.
AB  - The mechanism for hepatic uptake of temocaprilat, an angiotensin-converting
      enzyme inhibitor that is predominantly excreted into bile was studied using
      isolated rat hepatocytes and COS-7 cells expressing the organic anion
      transporting polypeptide (oatp1). The uptake of temocaprilat into isolated rat
      hepatocytes exhibited saturation with a Km of 20.9 microM and a Vmax of 0.21
      nmol/min/mg protein. This uptake was temperature sensitive and was significantly
      reduced by metabolic inhibitors, a sulfhydryl-modifying reagent and an anion
      exchange inhibitor, although the replacement of Na+ with Li+ in the medium did
      not affect the uptake. [3H]Temocaprilat uptake was inhibited by estradiol-17beta
      D-glucuronide and dibromosulphophthalein, typical substrates for the Na+
      independent organic anion transporter, in a concentration-dependent manner,
      whereas excess estradiol-17beta-D-glucuronide did not completely inhibit the
      uptake. Temocaprilat uptake into COS-7 cells transfected with oatp1 cDNA revealed
      a concentration-dependency with a Km of 46.7 microM, a value comparable with that
      obtained in isolated hepatocytes. The contribution of oatp1 to carrier-mediated
      hepatic uptake of temocaprilat was less than 50% by correcting the uptake
      clearance with that of estradiol-17beta-D-glucuronide. A good linear correlation
      was observed for the inhibitory effect of angiotensin-converting enzyme
      inhibitors (benazeprilat, cilazaprilat, delaprilat and enalaprilat) between
      isolated hepatocytes and oatp1-expressing cells. These data suggest that oatp1,
      along with another transporter(s), mediates the uptake of angiotensin-converting
      enzyme inhibitors into rat hepatocytes.

PMID- 9765320
TI  - Sch 50971, an orally active histamine H3 receptor agonist, inhibits central
      neurogenic vascular inflammation and produces sedation in the guinea pig.
AB  - We studied the actions of Sch 50971, a novel histamine H3 receptor agonist, in an
      experimental neurogenic model of migraine and characterized its sedative and
      respiratory actions. Sch 50971 (i.v. and p.o) inhibited plasma protein
      extravasation in the dura mater of guinea pigs after electrical stimulation of
      the trigeminal ganglia. The minimum effective doses of Sch 50971 were 3.0 mg/kg
      i.v. and 10 mg/kg p.o., which produced a 40% and 42% decrease in plasma protein
      extravasation, respectively. The effects of Sch 50971 (3.0 mg/kg i.v. ) were
      blocked by the histamine H3 antagonist thioperamide (3.0 mg/kg i.v.). The 5-HT1D
      agonist, sumatriptan (0.3 mg/kg i.v.), and the histamine H3 agonist, (R)-alpha
      methylhistamine (0.3 mg/kg), also inhibited plasma extravasation by 40 and 46%.
      In sedation studies, Sch 50971 (1-100 mg/kg p.o.) potentiated pentobarbital
      induced sleep. The ED40 min for Sch 50971, the benzodiazepines triazolam and
      diazepam, the histamine H1 antagonist diphenhydramine and the H3 receptor agonist
      (R)-alpha-methylhistamine were 7.0, 0.5, 2.3, 14.1 and 23.4 mg/kg p. o.,
      respectively. The sedative effects of oral Sch 50971 was blocked by thioperamide
      (10 microgram i.c.v.). The sedative activity of Sch 50971 was also examined using
      EEG activity, locomotor activity and sleep. In conscious guinea pigs, Sch 50971
      (10 mg/kg p.o.) depressed locomotor activity, increased total sleep time and
      produced EEG patterns consistent with physiological sleep. Sch 50971 decreased
      beta wave activity but had no effects on delta wave activity, theta activity or
      alpha wave activity. In contrast, triazolam (1.0 mg/kg p. o.) depressed delta and
      theta wave activity and produced large increases in alpha and beta wave activity.
      In conclusion, Sch 50971 is an orally active, potent and selective agonist of
      histamine H3 receptors that may act to ameliorate the sequelae of migraine
      headaches, where activation of histamine H3 receptors may be beneficial. Sch
      50971 also decreases motor activity and promotes EEG activity consistent with
      physiological sleep.

PMID- 9765321
TI  - Effects of acute and repeated administration of amisulpride, a dopamine D2/D3
      receptor antagonist, on the electrical activity of midbrain dopaminergic neurons.
AB  - Electrophysiological techniques were used to study the effects of amisulpride, a
      D2/D3 dopamine receptor blocker, on the activity of dopaminergic neurons in the
      substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA).
      Administration of single bolus doses of amisulpride (8-32 mg/kg i.v.) induced a
      dose-dependent increase in the basal activity of dopaminergic neurons, in both
      the SNc and the VTA. The effect of amisulpride was more evident in the VTA, where
      it elicited a maximal excitation of 38.5 +/- 12%, whereas in the SNc it caused a
      peak excitation of only 22.1 +/- 9.8%. Amisulpride also increased the bursting
      activity of dopaminergic neurons in the VTA but not in the SNc.
      Microiontophoretic application of amisulpride (10-40 nA) into the SNc and the VTA
      caused an increase in the basal firing rate of the majority of dopaminergic
      neurons sampled. The excitation induced by 40 nA amisulpride was more marked in
      the VTA (36.1 +/- 21%) than in the SNc (25.0 +/- 18%). Moreover,
      microiontophoretic amisulpride (40 nA) increased the bursting activity of
      dopaminergic neurons in the VTA only. Repeated administration of amisulpride (20
      and 50 mg/kg i.p.) for 21 consecutive days produced a significant decrease in the
      number of spontaneously active dopaminergic neurons in the VTA but not in the
      SNc. Repeated admistration of haloperidol (0.5 mg/kg i.p. ) decreased the number
      of dopaminergic cells both in the SNc and the VTA. The effect of repeated
      admistration of amisulpride on the activity of VTA dopaminergic neurons was
      reversed by apomorphine, suggesting that these neurons were probably under a
      state of depolarization block. Taken together, these data confirm previous
      findings indicating that low doses of amisulpride preferentially increase
      dopaminergic transmission in the mesolimbic system. Moreover, results obtained
      from long-term experiments are consistent with clinical data indicating that
      amisulpride given at high doses is an effective antipsychotic agent, associated
      with a low incidence of extrapyramidal side effects.

PMID- 9765322
TI  - Imidazenil, a positive allosteric GABAA receptor modulator, inhibits the effects
      of cocaine on locomotor activity and extracellular dopamine in the nucleus
      accumbens shell without tolerance liability.
AB  - Imidazenil, a benzodiazepine recognition site ligand that acts as partial
      positive allosteric modulator of gamma-aminobutyric acid (GABA) action at GABAA
      receptors, inhibits in a dose-dependent manner (0.56-2.5 micromol/kg i.p. to
      rats) the cocaine-induced increase in dopamine (DA) content in the dialysates of
      the nucleus accumbens shell and striatum and also inhibits cocaine-induced
      locomotor activity. Diazepam, a full allosteric modulator of GABA action at GABAA
      receptors, in a dose of 4.4 micromol/kg i.p. also attenuates the cocaine-induced
      increase in DA content in the dialysates of nucleus accumbens shell, and striatum
      and the cocaine-induced locomotor activity. However, imidazenil (2.5 micromol/kg
      i.p.) fails to reduce spontaneous locomotor activity, whereas diazepam (4.4
      micromol/kg i.p.) elicits sedation and ataxia and clearly impairs spontaneous
      locomotor activity. When added in vitro, both imidazenil and diazepam potentiate
      the GABA-mediated reduction of the ventral tegmental area DA neuron firing rate.
      After protracted treatment (14 days/three times a day with an increasing-dose
      schedule), the inhibitory actions of imidazenil fail to develop tolerance,
      whereas the actions of diazepam exhibit high tolerance liability. We conclude
      that imidazenil is devoid of tolerance liability and that, via a GABAA-mediated
      reduction in the extracellular DA in nucleus accumbens shell, it might reduce the
      psychomotor activity and reinforcing properties of cocaine.

PMID- 9765323
TI  - Pharmacokinetics and biological actions of subcutaneously administered human
      brain natriuretic peptide.
AB  - Human brain natriuretic peptide (hBNP) has demonstrated favorable hemodynamic
      effects in patients with congestive heart failure; however, the peptidic nature
      of this compound has focused clinical testing on protocols involving intravenous
      delivery. We have studied subcutaneous delivery as an alternative method of
      administering hBNP. Administration of 30 microgram/kg hBNP by either subcutaneous
      or intravenous delivery protocols resulted in significant hBNP-immunoreactive
      material in the plasma with area under the plasma concentration-time curve values
      of 310 +/- 20 nmolxmins/liter and 187 +/- 47 nmolxmins/liter, respectively.
      Plasma cyclic GMP, a surrogate marker of activation of the biological receptor
      for hBNP, was elevated for a longer period of time following subcutaneous
      delivery compared with intravenous delivery. Subcutaneous delivery of 30
      microg/kg hBNP resulted in natriuresis, diuresis and reduced systolic blood
      pressure in anesthetized normotensive rabbits, effects similar in magnitude yet
      prolonged in duration compared with those elicited by the same dose of hBNP
      delivered intravenously. Systolic blood pressure following hBNP treatment
      remained below base-line values for 50 and 150 min following intravenous and
      subcutaneous delivery protocols, respectively. These results suggests that
      subcutaneous delivery of hBNP may be a viable therapeutic alternative to
      intravenous modes of delivery.

PMID- 9765324
TI  - Corticosterone facilitates the acquisition of cocaine self-administration in
      rats: opposite effects of the type II glucocorticoid receptor agonist
      dexamethasone.
AB  - The effect of corticosterone on the acquisition of cocaine-seeking behavior was
      investigated in rats using ascending dose-response curves for intravenous cocaine
      self-administration. Rats pretreated daily with corticosterone (2.0 mg/kg i.p.)
      acquired cocaine self-administration at a lower dose compared with vehicle
      treated controls. In contrast, daily corticosterone pretreatment did not alter
      food-maintained responding. Cocaine self-administration was not affected by the
      type I (mineralocorticoid) receptor agonist, aldosterone (100 microgram/kg).
      However, rats treated with the type II (glucocorticoid) receptor agonist,
      dexamethasone (10 or 100 microgram/kg) did not acquire self-administration at any
      dose tested. The 100 microgram/kg dose of dexamethasone attenuated food
      reinforced behavior and decreased body weight, but these effects were not
      observed with the 10 microgram/kg dose. Dexamethasone dose-dependently attenuated
      the plasma corticosterone response to self-administered infusions or
      intraperitoneal injections of cocaine, indicating that the ability of
      dexamethasone to block cocaine-induced corticosterone secretion may have
      contributed to its effects on self-administration. Administration of aldosterone
      (100 microgram/kg) together with 10 microgram/kg dexamethasone restored self
      administration to the level of vehicle-treated rats, suggesting that type I
      receptor occupation by corticosterone may be required for the acquisition of this
      behavior. These results indicate that stress-induced corticosterone secretion may
      provide a substrate through which stressors interact with cocaine reinforcement.
      Additionally, the finding that dexamethasone blocks the acquisition of cocaine
      self-administration may be relevant to the development of novel approaches to the
      treatment of cocaine addiction.

PMID- 9765325
TI  - Antagonism by class I antiarrhythmic drugs of levcromakalim-induced relaxation in
      isolated rat aorta.
AB  - We have analyzed the effects of several class I antiarrhythmic drugs
      (propafenone, quinidine, its enantiomer quinine, disopyramide, flecainide and
      mexiletine), tetraethylammonium (TEA) and glibenclamide on the vasodilator
      effects of the adenosine 5'-triphosphate-dependent K+ channels channel opener
      levcromakalim in isolated rat aorta precontracted by 30 mM KCl. TEA (>1 mM) and
      disopyramide (>/=10 microM), induced a sustained contraction in resting aortic
      rings. Propafenone (>/=3 microM), quinidine (>/=30 microM), disopyramide (>/=100
      microM) and flecainide (>/=100 microM) but not the other drugs decreased the
      contraction induced by 30 mM KCl in a concentration-dependent manner. Propafenone
      (>/=1 microM), quinidine (>/=10 microM), quinine (>/=1 microM), disopyramide
      (>/=3 microM), flecainide (>/=100 microM), mexiletine (>/=3 microM), TEA (>/=0.3
      mM) and glibenclamide (>/=0.1 microM) caused a concentration-dependent inhibition
      of the vasodilation induced by levcromakalim in rat aortic rings. The order of
      potency of the drugs, expressed as pD2 values, to inhibit the vasodilation
      induced by 0.3 microM levcromakalim was the following: glibenclamide (6.84) >
      quinine (6.14) > propafenone (5.27) > disopyramide (5.03) > quinidine (4.80) >
      mexiletine (4.68) > flecainide (3.37) > TEA (3. 20). With the exception of
      flecainide and mexiletine, the slopes of the Schild plots were similar to unity.
      Based on the mode of antagonism these drugs could be classified in four groups:
      1) glibenclamide which only shifted the curves to the right, 2) quinidine and
      disopyramide that, at low concentrations, shifted the curve to the right but, at
      higher concentrations, it also reduced the maximal relaxant effect, 3)
      propafenone, quinine and TEA that shifted the curve rightwards and reduced the
      maximal relaxation at all concentrations and 4) flecainide and mexiletine whose
      Schild slopes were clearly different from unity. In conclusion, class I
      antiarrhythmic drugs inhibited levcromakalim-induced relaxation in isolated rat
      aorta. The concentrations at which these effects were observed were within the
      therapeutic range (except for flecainide) and similar to those reported to
      inhibit adenosine 5'-triphosphate-dependent K+ channel currents. Analysis of the
      concentration-response curves revealed that these drugs produced a noncompetitive
      antagonism of levcromakalim-induced relaxations.

PMID- 9765326
TI  - Evidence for a causative role of N-methyl-D-aspartate receptors in an in vitro
      model of alcohol withdrawal hyperexcitability.
AB  - Synaptic mechanisms underlying hyperexcitability due to withdrawal from chronic
      ethanol exposure were investigated in a hippocampal explant model system using
      electrophysiological techniques. Whole-cell voltage clamp recordings from CA1
      pyramidal cells demonstrated that acute ethanol exposure inhibited N-methyl-D
      aspartate receptor (NMDAR)-mediated excitatory postsynaptic currents by over 40%.
      Chronic ethanol exposure for 6 to 11 days at 35 or 75 mM induced no differences
      from control explants in the fast component of the population synaptic response
      (non-NMDAR-mediated). Prolonged field potential recordings (to 10 hr) were used
      to monitor the withdrawal process in vitro. Ethanol-exposed explants from both 35
      and 75 mM groups displayed an increase (60% and 89%, respectively) in the NMDAR
      mediated component of synaptic transmission on withdrawal from chronic exposure.
      Prolonged tonic-clonic electrographic seizure activity was consistently observed
      after ethanol withdrawal only after the increase in NMDAR function. This
      hyperexcitability was inhibited by the NMDAR antagonist D-2-amino-5
      phosphonovaleric acid and returned once the NMDAR component was reestablished
      after antagonist washout. In situ hybridization studies suggest that expression
      of NR2B subunit mRNA may be enhanced in explants after chronic ethanol exposure.
      No lasting differences were observed in the NMDAR component after acute in vitro
      ethanol exposure and withdrawal. These data suggest that the occurance of ethanol
      withdrawal hyperexcitability in this system may be directly dependent on
      alterations in NMDAR function after chronic exposure. Since this region and
      others that contain ethanol sensitive NMDARs may serve as epileptic foci, long
      term alterations in NMDAR function may be expected to generate paroxysmal
      depolarizing shifts underlying ictal events after withdrawal from ethanol
      exposure.

PMID- 9765327
TI  - Calcium source diversity in canine lower esophageal sphincter muscle.
AB  - Tonic contraction of the lower esophageal sphincter (LES) prevents
      gastroesophageal reflux. LES tone is produced both by cholinergic nerve and
      myogenic activities. The Ca++ sources for LES tone and carbachol-induced
      contraction in canine LES strips were determined from the effect on contractile
      activity of extracellular Ca++ level modulation, Ca++ entrance blockade or
      enhancement with nifedipine or BayK8644 respectively, and/or inhibition of Ca++
      store refilling using the sarcoplasmic reticulum Ca++ pump inhibitor,
      cyclopiazonic acid. LES tone disappeared when a Ca++-free physiological saline
      solution or nifedipine was applied. Sustained Ca++ free contractions to carbachol
      were prevented/abolished by nifedipine or increased Ca++ chelation and enhanced
      by BayK8644. Inhibition of sarcoplasmic reticulum Ca++ pumps by cyclopiazonic
      acid reduced Ca++ free contractions to carbachol; BayK8644 restored cyclopiazonic
      acid-reduced Ca++ free contractions to carbachol. Therefore, some Ca++ stores can
      be refilled by mechanisms not requiring activity of the sarcoplasmic reticulum
      Ca++ pump. A preferred pathway may exist whereby Ca++ enters stores directly
      through L-Ca++ channels. The proposed Ca++ store refilling mechanism involves
      continuous Ca++ entry through L-Ca++ channels from sites not equilibrated with
      external Ca++. Therefore, diverse Ca++ stores exist in canine LES which are
      dependent on Ca++ influx through L-Ca++ channels.

PMID- 9765328
TI  - The effects of methamphetamine on the production of free radicals and oxidative
      stress.
AB  - The effects of methamphetamine (METH) on pro-oxidant processes and on the
      production of reactive oxygen species were examined in vivo in the rat brain. The
      presence of oxidative damage in striatum, as revealed by the oxidation of lipid,
      also was assessed via the measurement of the lipid peroxidation product
      malonyldialdehyde. To elucidate further the mechanisms mediating METH-induced
      oxidative stress, we studied the possible reversal of the long-term METH-induced
      decrease in striatal dopamine content by antioxidants through iron chelation and
      trapping of free radicals. The uric acid concentration in the striata of rats
      killed 1 hr, but not 24 hr, after a four-injection regimen of METH was increased
      significantly compared with saline-injected control rats. METH increased the in
      vivo formation of the hydroxylated products of salicylate and d-phenylalanine, as
      evidenced by the elevated extracellular concentrations of 2,3 dihydroxybenzoic
      acid and p-tyrosine, respectively. The local perfusion of the striatum with the
      iron chelator deferroxamine attenuated the long-term depletions of striatal
      dopamine content produced by METH. In other experiments, malonyldialdehyde
      concentrations in incubated striatal homogenates were elevated significantly in
      METH-treated rats. Finally, pretreatment with the spin trapping agent
      phenylbutylnitrone before the METH injections attenuated the subsequent long-term
      depletions in striatal dopamine content. Overall, the results illustrate that
      METH increases pro-oxidant processes and offer supportive evidence that METH
      produces oxidative damage. These studies also demonstrate that iron may be
      involved in mediating the long-term damage to dopamine neurons after repeated
      administrations of METH.

PMID- 9765329
TI  - Stimulation of cholesterol release from rabbit foam cells by the action of a new
      inhibitor for acyl CoA:cholesterol acyltransferase (ACAT), HL-004.
AB  - A new inhibitor of acyl CoA:cholesterol acyltransferase (ACAT), HL-004 [N-(2, 6
      diisopropylphenyl)tetradecylthioacetamide], suppressed the synthesis of
      cholesterol [14C]oleate at 10(-9) approximately 10(-7) M in a concentration
      dependent manner in both THP-1 cell-derived macrophages and foam cells prepared
      from aortic intima of rabbits fed a high cholesterol diet. Incorporation of
      [3H]cholesterol oleate-beta very low density lipoproteins was not inhibited by HL
      004 at 10(-9) approximately 10(-7) M. Release of radioactivity from the cells
      loaded with [3H]cholesterol oleate-beta very low density lipoproteins was
      increased by the inhibition of ACAT activity with HL-004. HL-004 did not affect
      on acid and neutral cholesterol esterases. As a result, cholesterol ester content
      in foam cells decreased. These data suggested that HL-004 decreases cholesterol
      ester in foam cells by increasing the release of cholesterol and therefore might
      suppress atherosclerotic lesions.

PMID- 9765330
TI  - The selective norepinephrine reuptake inhibitor, LY368975, reduces food
      consumption in animal models of feeding.
AB  - The compound, LY368975 ((R)-thionisoxetine) is a potent and selective inhibitor
      of the norepinephrine (NE) reuptake site. We evaluated the in vivo properties of
      LY368975 in various animal models. In mice, LY368975 prevented heart NE depletion
      by 6-hydroxydopamine with an ED50 of 1.22 mg/kg. In rats, orally administered
      LY368975 inhibited 3H-NE uptake into hypothalamic synaptosomes ex vivo with an
      ED50 of 2.5 mg/kg and 3H-tomoxetine binding to the NE transporter with an ED50 of
      2.7 mg/kg. When rats were deprived of food for 18 hr, 10 mg/kg LY368975 was able
      to suppress food intake 1, 2 and 4 hr after reintroduction of the feed. In
      nonfasted rats trained to drink sweetened condensed milk, LY368975 produced a
      dose-dependent reduction in consumption with a 44% decrease at 3 mg/kg. At doses
      up to 10 mg/kg p.o., LY368975 produced no significant effects on locomotor
      activity suggesting the compound does not activate or sedate the animals at
      pharmacologically relevant doses. Therefore, LY368975 is an orally available and
      centrally active NE reuptake inhibitor that is capable of reducing food
      consumption in rodents. Compounds of this class may have use in the treatment of
      obesity and eating disorders.

PMID- 9765331
TI  - Epithelial ion transport and barrier abnormalities evoked by superantigen
      activated immune cells are inhibited by interleukin-10 but not interleukin-4.
AB  - Many studies have indicated an association between bacteria and the severity of
      enteric secretory or inflammatory disorders. We previously showed that monolayers
      of human T84 epithelial cells display altered ion transport and permeability
      after coculture with Staphylococcus aureus enterotoxin B (SEB, a model
      superantigen)-activated immune cells, where interferon-gamma and tumor necrosis
      factor-alpha were key mediators in the pathophysiology. Here we examined whether
      the regulatory Th2-type cytokines, interleukin (IL)-10 and IL-4, could prevent
      these epithelial irregularities. T84 monolayers were cocultured with human
      peripheral blood mononuclear cells (PBMC) or T cell-enriched, monocyte-depleted
      PBMC (T + B cells) +/- SEB for 20 hr in the presence or absence of IL-10 or IL-4.
      Subsequently, T84 monolayers were mounted in Ussing chambers and ion transport
      (short-circuit current (Isc) and DeltaIsc evoked by forskolin) and permeability
      (ion resistance and probe fluxes) were assessed. IL-10 dose-dependently inhibited
      the increased T84 permeability and the reduced responsiveness to forskolin that
      were evoked by coculture with SEB-activated PBMC or T + B cells. Similar changes
      in T84 function occurred in response to conditioned medium from SEB-activated
      immune cells; however, addition of IL-10 to the conditioned medium did not
      prevent the changes in epithelial function. In contrast, when PBMC were
      stimulated with SEB in the presence of IL-10, the subsequent conditioned medium
      was less effective in evoking altered epithelial function. These data suggest
      that the affect of IL-10 was due to effects on the immune cells and not directly
      on the epithelium. In contrast to IL-10, IL-4 did not ameliorate any of the
      immune-mediated changes in T84 function. We conclude that IL-10 can reduce the
      epithelial functional changes caused by SEB-activated immune cells and this data
      adds further support for IL-10 immunotherapy in the treatment of intestinal
      secretory or inflammatory disorders.

PMID- 9765332
TI  - Inflammation modifies the role of cyclooxygenases in the contractile responses of
      the rat detrusor smooth muscle to kinin agonists.
AB  - The contractile responses elicited by the selective kinin B1 and B2 receptor
      agonists [desArg9]-bradykinin ([desArg9]-BK) and [Hyp3, Tyr(Me)8]-bradykinin
      ([Hyp3, Tyr(Me)8]-BK) (1 nM-10 microM), respectively, were evaluated in control
      vs. inflamed (cyclophosphamide 150 mg kg-1 i.p., 48 h before the sacrifice) rat
      isolated urinary bladder strips. The contractile responses to the B2 receptor
      agonist did not differ in control vs. inflamed bladders, whereas the contractile
      responses to [desArg9]-BK were potentiated in inflamed bladders. The selective B1
      and B2 receptor antagonists B 9858 (H-Lys-Lys-Arg-Pro-Hyp-Gly-Igl-Ser-DIgl-Oic
      OH) and Hoe 140 (H-DArg-Arg-Pro-Hyp-Gly-Thi-Ser-DTic-Oic-Arg-OH), both at 1
      microM, inhibited the response to the B1 and B2 receptor agonists, respectively,
      in both control and inflamed bladders. In addition, the concentration-response
      curve to [Hyp3, Tyr(Me)8]-BK was shifted to the right and depressed by B 9858 in
      inflamed bladders. The nonselective cyclooxygenase (COX) inhibitors S-(-)
      ketoprofen (10 microM) and piroxicam (30 microM) markedly depressed the
      concentration-response curves to [desArg9]-BK and [Hyp3, Tyr(Me)8]-BK in control
      bladders, but neither drug affected the B1 or B2 receptor agonist-mediated
      responses in inflamed bladders. The selective inhibitor of the inducible COX-2
      isoenzyme, NS-398 (1 microM), did not inhibit the contractile responses to
      [desArg9]-BK and [Hyp3, Tyr(Me)8]-BK in either control or inflamed bladders,
      whereas it significantly potentiated the response to the B1 receptor agonist in
      inflamed bladders. The exogenous administration of prostaglandin E2 (PGE2)
      induced S-(-)-ketoprofen-resistant contractile responses that were depressed in
      inflamed bladders. Pretreatment with S-(-)-ketoprofen restored the PGE2-mediated
      contractile responses of inflamed bladders to control values. PGE2 assay revealed
      that the basal production of PGE2 is significantly higher after inflammation than
      in control conditions. [desArg9]-BK and [Hyp3, Tyr(Me)8]-BK (1 microM each) both
      stimulated PGE2 production, and their effect was larger in inflamed than in
      control bladders. Piroxicam (30 microM) prevented the PGE2 production evoked by
      [desArg9]-BK in both control and inflamed bladders and likewise abolished that
      produced by [Hyp3, Tyr(Me)8]-BK. NS-398 (1 microM) reduced the PGE2 production
      elicited by [desArg9]-BK in control and inflamed bladders. When NS-398 was tested
      on the [Hyp3, Tyr(Me)8]-BK-induced PGE2 production, it inhibited PGE2 production
      in the inflamed bladders only, without significantly modifying the response
      obtained in controls. These findings demonstrate that 1) in normal bladders, the
      activation of B1 and B2 receptors evokes contraction that is largely mediated by
      COX-1 metabolites, whereas the COX-2 appears to be involved in PGE2 production
      after the activation of B1 receptor only, without interfering with contraction,
      and 2) in inflamed bladders, the activation of B1 and B2 receptors still produce
      PGE2, but the contractile response is not reduced by COX inhibitors, a result
      that indicates that additional mechanisms play a compensatory role.

PMID- 9765333
TI  - Central GABAA and GABAB receptor modulation of basal and stress-induced plasma
      interleukin-6 levels in mice.
AB  - To investigate the modulatory roles of central gamma-aminobutyric acid (GABA)A
      and GABAB receptors in the regulation of basal and stress-induced plasma
      interleukin-6 (IL-6) levels, we examined the effects of i.c.v. injection of GABA
      receptor agonists and antagonists on basal and restraint stress-induced plasma IL
      6 levels in mice. Muscimol (20-200 ng), a GABAA receptor agonist, and baclofen (5
      20 ng), a GABAB receptor agonist, injected i.c.v. did not affect the basal levels
      of plasma IL-6. In the restraint-stressed animals, muscimol and baclofen
      inhibited the stress-induced plasma IL-6 levels from the dose of 50 and 15 ng,
      respectively. 2-(3-Carboxyl)-3-amino-6-(4-methoxyphenyl)-pyridazinium bromide (SR
      95,531; 0.3-10 ng), a GABAA receptor antagonist, and 2-hydroxysaclofen (1-10
      microgram), a GABAB receptor antagonist, injected i.c.v. increased both the basal
      and the restraint stress-induced plasma IL-6 levels. The i.p. pretreatment of
      animals with 6-hydroxydopamine (100 mg/kg) for 3 days significantly inhibited SR
      95,531 (3 ng i.c.v.)- but not 2-hydroxysaclofen (10 microg i.c.v.)-induced
      increase in the basal plasma IL-6 levels. These data suggest that central GABAA
      and GABAB receptors are involved in the suppressive modulation of basal and
      restraint stress-induced plasma IL-6 levels in mice.

PMID- 9765334
TI  - Exogenous leukotriene B4 (LTB4) inhibits human neutrophil generation of LTB4 from
      endogenous arachidonic acid during opsonized zymosan phagocytosis.
AB  - The effect of exogenous leukotriene B4 (LTB4) on opsonized zymosan-stimulated
      human neutrophil formation of 5-lipoxygenase products and arachidonic acid
      release was directly assessed using reverse-phase HPLC/tandem mass spectrometric
      methods for quantitation. Stable isotopically labeled LTB4, [1,2-13C2]LTB4,
      caused a dose-dependent inhibition of LTB4 production in isolated human
      neutrophils with significant inhibition (60 +/- 7% of control levels) when 0.12
      nM [13C2]LTB4 was present. Production of 5-hydroxy-6,8,11,14-eicosatetraenoic
      acid and release of free arachidonic acid were also dose-dependently inhibited by
      exogenous LTB4. Metabolites of LTB4, 20-hydroxy-LTB4 and 3(S)-hydroxy-LTB4, also
      significantly reduced LTB4 production to levels as low as 10 +/- 6% and 10 +/- 7%
      of control levels, respectively, when present exogenously at 10 nM. Exogenous 5
      hydroxy-6,8,11,14-eicosatetraenoic acid at concentrations as high as 10 nM
      produced no significant reduction in LTB4 biosynthesis during zymosan-stimulated
      human neutrophil production of LTB4. The inhibitory effect of LTB4 could be
      partially reversed by the LTB4 receptor antagonist U 75302. Furthermore, an
      alternative stimulus, N-formyl-methionyl-leucyl-phenylalanine (100 nM), did not
      inhibit the production of LTB4 in opsonized zymosan-stimulated human neutrophils.
      These results suggest that activation of the LTB4 receptor on the human
      neutrophil during phagocytosis limits the ultimate biosynthesis of LTB4. This
      autocrine effect is opposite to that observed when neutrophils have much of the
      signal transduction pathways bypassed when stimulated with calcium ionophore
      A23187 or treated with exogenous free arachidonic acid.

PMID- 9765335
TI  - Novel, selective delta6 or delta5 fatty acid desaturase inhibitors as
      antiinflammatory agents in mice.
AB  - Decreased synthesis of arachidonic acid by inhibition of the Delta6 or Delta5
      desaturase was evaluated as a means to mitigate inflammation. Using quantitative
      in vitro and in vivo radioassays, novel compounds representing five classes of
      Delta5 desaturase inhibitors and one class of Delta6 desaturase inhibitor were
      identified. The Delta6 desaturase inhibitor, SC-26196, had pharmacokinetic and
      pharmacodynamic profiles in mice that allowed for the evaluation of the
      pharmacological effects of chronic inhibition of desaturase activity. SC-26196
      decreased edema to the same extent as indomethacin or essential fatty acid
      deficiency in the carrageenan paw edema model in the mouse. The antiinflammatory
      properties of SC-26196 were consistent with its mechanism of action as a Delta6
      desaturase inhibitor: 1) A correlation existed between inhibition of liver Delta6
      desaturase activity and decreases in edema. 2) The onset of the decrease in edema
      was time dependent. 3) Selective reduction of arachidonic acid occurred dose
      dependently in liver, plasma and peritoneal cells. 4) In the presence of SC
      26196, controlled refeeding of arachidonic acid, but not oleic acid, reversed the
      changes resulting from desaturase inhibition. The Delta6 desaturase may be a
      target for development of antiinflammatory drugs whose mechanism of action is
      unique.

PMID- 9765336
TI  - S 18126 ([2-[4-(2,3-dihydrobenzo[1,4]dioxin-6-yl)piperazin-1-yl methyl]indan-2
      yl]), a potent, selective and competitive antagonist at dopamine D4 receptors: an
      in vitro and in vivo comparison with L 745,870 (3-(4-[4-chlorophenyl]piperazin-1
      yl)methyl-1H-pyrrolo[2, 3b]pyridine) and raclopride.
AB  - The novel benzoindane S 18126 possessed > 100-fold higher affinity at cloned,
      human (h) D4 (Ki = 2.4 nM) vs. hD2 (738 nM), hD3 (2840 nM), hD1 (> 3000 nM) and
      hD5 (> 3000 nM) receptors and about 50 other sites, except sigma1 receptors (1.6
      nM). L 745,870 similarly showed selectivity for hD4 (2.5 nM) vs. hD2 (905 nM) and
      hD3 (> 3000 nM) receptors. In contrast, raclopride displayed low affinity at hD4
      (> 3000 nM) vs. hD2 (1.1 nM) and hD3 receptors (1.4 nM). Stimulation of [35S]
      GTPgammaS binding at hD4 receptors by dopamine (DA) was blocked by S 18126 and L
      745,870 with Kb values of 2.2 and 1.0 nM, respectively, whereas raclopride (>
      1000 nM) was inactive. In contrast, raclopride inhibited stimulation of [35S]
      GTPgammaS binding at hD2 sites by DA with a Kb of 1.4 nM, whereas S 18126 (> 1000
      nM) and L 745,870 (> 1000 nM) were inactive. As concerns presynaptic dopaminergic
      receptors, raclopride (0.01-0.05 mg/kg s.c. ) markedly enhanced DA synthesis in
      mesocortical, mesolimbic and nigrostriatal dopaminergic pathways. In contrast,
      even high doses (2. 5-40.0 mg/kg s.c.) of S 18126 and L 745,870 were only weakly
      active. Similarly, raclopride (0.016 mg/kg i.v.) abolished inhibition of the
      firing rate of ventrotegmental dopaminergic neurons by apomorphine, whereas even
      high doses (0.5 mg/kg i.v.) of S 18126 and L 745,870 were only weakly active. As
      regards postsynaptic dopaminergic receptors, raclopride potently (0.01-0.3 mg/kg
      s.c.) reduced rotation elicited by quinpirole in rats with unilateral lesions of
      the substantia nigra, antagonized induction of hypothermia by PD 128, 907,
      blocked amphetamine-induced hyperlocomotion and was effective in six further
      models of potential antipsychotic activity. In contrast, S 18126 and L 745,870
      were only weakly active in these models (5.0-> 40.0 mg/kg s.c.). In six models of
      extrapyramidal and motor symptoms, such as induction of catalepsy, raclopride was
      likewise potently active (0.01-2.0 mg/kg s.c.) whereas S 18126 and L 745,870 were
      only weakly active (10.0-80.0 mg/kg s.c.). In freely moving rats, raclopride
      (0.16 mg/kg s.c.) increased levels of DA by + 55% in dialysates of the frontal
      cortex. However, it also increased levels of DA in the accumbens and striatum by
      70% and 75%, respectively. In contrast to raclopride, at a dose of 0.16 mg/kg
      s.c. , neither S 18126 nor L 745,870 modified frontal cortex levels of DA.
      However, at a high dose (40.0 mg/kg s.c.), S 18126 increased dialysate levels of
      DA (+ 85%) and noradrenaline (+ 100%), but not serotonin (+ 10%), in frontal
      cortex without affecting DA levels in accumbens (+ 10%) and striatum (+ 10%). In
      conclusion, S 18126 and L 745,870 behave as potent and selective antagonists of
      cloned, hD4 vs. other dopaminergic receptor types in vitro. However, their in
      vivo effects at high doses probably reflect residual antagonist actions at D2 (or
      D3) receptors. Selective blockade of D4 receptors was thus associated neither
      with a modification of dopaminergic transmission nor with antipsychotic
      (antiproductive) or extrapyramidal properties. The functional effects of
      selective D4 receptor blockade remain to be established.

PMID- 9765337
TI  - A comparative in vitro and in vivo pharmacological characterization of the novel
      dopamine D3 receptor antagonists (+)-S 14297, nafadotride, GR 103,691 and U
      99194.
AB  - The benzofurane (+)-S 14297, the benzamide nafadotride, the aminoindane U 99194
      and the arylpiperazine GR 103,691 have been proposed as "selective" antagonists
      at dopamine D3 vs. D2 receptors. Herein, we compared their in vitro affinities
      and in vivo actions to those of the aminotetralin D3 antagonists (+)-AJ 76 and
      (+)-UH 232. Affinities at recombinant, human (h)D3 and/or hD2 sites were
      determined by employing the mixed D2/D3 antagonist [125I]-iodosulpride and the
      preferential D3 ligands [3H]-(+)-PD 128, 907 and [3H]-(+)-S 14297. [3H]-(+)-PD
      128,907, [3H]-(+)-S 14297 and [125I]-iodosulpride yielded an essentially
      identical pattern of displacement at D3 sites, which suggests that they recognize
      the same population of receptors. The rank order of potency (Ki values in nM vs.
      [3H]-(+)-PD 128,907) was GR 103,691 (0.4) approximately nafadotride (0.5) >
      haloperidol (2) approximately (+)-UH 232 (3) approximately (+)-S 14297 (5) > (+)
      AJ 76 (26) > U 99194 (160). The rank order of preference (Ki ratio, D2:D3) for D3
      receptors (labeled by [3H]-PD 128,907) vs. D2 sites (labeled by [125I]
      iodosulpride) was (+)-S 14297 (61) approximately GR 103,691 (60) > U 99194 (14) >
      nafadotride (9) approximately (+)-UH 232 (8) approximately (+)-AJ 76 (6) >
      haloperidol (0.2). (+)-S 14297 and GR 103,691 also showed greater than 100-fold
      selectivity at dopamine hD3 vs. hD4 and hD1 sites. However, GR 103,691 showed
      marked affinity for serotonin1A receptors (5.8 nM) and alpha-1 adrenoceptors
      (12.6 nM). In vivo, all antagonists except GR 103,691 prevented the induction of
      hypothermia by (+)-PD 128,907 (0.63 mg/kg s.c.) and a further preferential D3
      agonist, (+)-7-OH-DPAT (0.16 mg/kg s.c.). On the other hand, haloperidol, (+)-AJ
      76, (+)-UH 232 and nafadotride all induced catalepsy in rats, whereas (+)-S
      14297, U 99194 and GR 103,691 were inactive. Haloperidol, (+)-AJ 76, (+)-UH 232,
      nafadotride and (weakly) U 99194 also enhanced prolactin secretion and striatal
      dopamine synthesis, whereas (+)-S 14297 and GR 103,691 were inactive. However,
      despite its high affinity at 5-HT1A receptors and alpha-1 adrenoceptors, both of
      which are present on raphe-localized serotonergic neurons, GR 103,691 (0.5 mg/kg
      i.v.) failed to influence their basal firing rate or the inhibition of their
      electrical activity by the 5-HT1A agonist (+/-)-8-OH-DPAT (0.005 mg/kg i.v.), a
      result that casts doubt on its activity in vivo. In conclusion, both (+)-S 14297
      and GR 103,691 are markedly selective ligands that permit the characterization of
      actions at hD3 vs. hD2 receptors in vitro, but (+)-S 14297 appears to be of
      greater utility for the evaluation of their functional significance in vivo.
      Nevertheless, to develop a better understanding of the respective roles of
      dopamine D3 and D2 receptors, we need additional, chemically diverse antagonists
      of improved potency and selectivity.

PMID- 9765338
TI  - Substituted 3beta-phenylethynyl derivatives of 3alpha-hydroxy-5alpha-pregnan-20
      one: remarkably potent neuroactive steroid modulators of gamma-aminobutyric acidA
      receptors.
AB  - Neuroactive steroids are positive allosteric modulators of gamma-aminobutyric
      acidA (GABAA) receptor complexes. Synthetic modification generally does not
      increase neuroactive steroid potency beyond that of the naturally occurring
      progesterone metabolite, 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-P).
      Recently, it has been shown that introduction of appropriately para-substituted
      phenylethynyl groups at the 3beta-position of 5beta steroids increases receptor
      potency. The present report presents the synthesis and pharmacological profile of
      an analogous series of 5alpha steroids. The most striking feature of this series
      is the further enhancement of in vitro and in vivo potency obtained. In
      particular, 3beta-(p-acetylphenylethynyl)-3alpha-hydroxy-5alpha-pr egnan-20-one
      (Co 152791) was 11-, 16- and 49-fold more potent than 3alpha, 5alpha-P in
      modulating the binding of [35S]TBPS, [3H]flunitrazepam and [3H]muscimol,
      respectively, in rat brain membranes (Co 152791 IC50 or EC50 = 2-7.5 nM).
      Similarly, Co 152791 was 3- to 20-fold more potent than 3alpha,5alpha-P as an
      inhibitor of [35S]TBPS binding in human recombinant receptor combinations
      containing alpha1, alpha2, alpha3 or alpha5 and beta2gamma2L subunits (Co 152791
      IC50 1.4-5.7 nM). Co 152791 displayed low efficacy and 3alpha,5alpha-P had low
      potency at alpha4/6beta3gamma2L GABAA receptor complexes. Interestingly, Co
      152791 demonstrated remarkable potency as a potentiator of GABA-evoked currents
      in Xenopus oocytes expressing alpha1beta2gamma2L receptors (EC50 0.87 nM), being
      184-fold more potent than 3alpha,5alpha-P. High in vitro potency was also
      reflected in enhanced in vivo activity in that Co 152791 exhibited exceptional
      anticonvulsant potency, protecting mice from pentylenetetrazol-induced seizures
      at a approximately 5-fold lower dose than 3alpha,5alpha-P after i.p.
      administration (Co 152791 ED50 0.6 mg/kg). Moreover, Co 152791 was orally active
      (ED50 1.1 mg/kg) and exhibited a therapeutic index of 7 relative to rotorod
      impairment. The remarkable potency of Co 152791 as a positive allosteric
      modulator of GABAA receptors may be explained by its interaction with an
      auxiliary binding pocket in the neuroactive steroid binding site. In addition,
      modification at the 3beta-position probably hinders metabolism of the 3alpha
      hydroxy group contributing to the exceptional anticonvulsant potency of this
      compound relative to other neuroactive steroids.

PMID- 9765339
TI  - Structural requirements for the hepatotoxicity of nonsteroidal anti-inflammatory
      drugs in isolated rat hepatocytes.
AB  - Hepatotoxicity is one of the common side effects of nonsteroidal anti
      inflammatory drugs (NSAIDs). We investigated the cytotoxicity of 18 acidic NSAIDs
      (3 salicylic acids, 3 anthranilic acids, 6 arylacetic acids, 6 arylpropionic
      acids) to freshly isolated rat hepatocytes as assessed by the NSAID-induced
      leakage of lactate dehydrogenase (LDH) in order to determine structural
      requirements for the direct hepatotoxicity of the NSAIDs. Diflunisal (salicylic
      acids), flufenamic acid, mefenamic acid, tolfenamic acid (anthranilic acids),
      diclofenac, indomethacin, acemetacin (arylacetic acids) and flurbiprofen
      (arylpropionic acids) caused significant LDH leakage, indicating that substituent
      position of a carboxyl group does not relate to the hepatotoxicity of the NSAIDs.
      Because the cytotoxic NSAIDs were of two types as classified by their "skeleton,"
      diphenyl and diphenylamine, we tested the cytotoxicity of the compounds. Diphenyl
      did not cause LDH leakage, but diflunisal, which has the diphenyl structure, was
      cytotoxic. On the other hand, diphenylamine induced LDH leakage to the same
      degree as diclofenac, which has the diphenylamine structure. Therefore,
      diphenylamine itself was suggested to be responsible for the cytotoxicity of
      diclofenac and anthranilic acids, whereas a substituted group(s) in addition to
      diphenyl structure seems to be important for diflunisal cytotoxicity. All of the
      cytotoxic NSAIDs and diphenylamine extensively decreased hepatocellular ATP
      content, whereas the noncytotoxic NSAID did not, indicating that the NSAID
      induced decrease in ATP, probably by their uncoupling effects on mitochondrial
      oxidative phosphorylation, is involved in the hepatotoxicity of the NSAIDs.

PMID- 9765340
TI  - A novel cardiotonic agent SCH00013 acts as a Ca++ sensitizer with no chronotropic
      activity in mammalian cardiac muscle.
AB  - We investigated the inotropic effect of SCH00013 (4, 5-dihydro-6-[1-[2-hydroxy-2
      (4-cyanophenyl)ethyl]-1,2,5, 6-tetrahydropyrido-4-yl]pyridazin-3(2H)-one) on
      isolated dog and rabbit ventricular muscles and in indo-1 loaded rabbit
      ventricular cardiomyocytes. SCH00013 elicited a positive inotropic effect in a
      concentration-dependent manner (10(-6) to 10(-4) M) in both species in the
      presence of bupranolol. The positive inotropic effects of 10(-4) M SCH00013 on
      the dog and rabbit were 38% and 29% of the maximal response to isoproterenol.
      SCH00013 did not alter the rate of beating in isolated rabbit right atria. In
      indo-1 loaded rabbit ventricular cardiomyocytes, SCH00013 at 10(-4) M increased
      the systolic cell shortening by 52% above the base-line value in association with
      an insignificant increase in the systolic fluorescence ratio by 15% above the
      control. SCH00013 shifted the relationship between the Ca++ transients and cell
      shortening to the left as compared with that of elevation of [Ca++]o. In the dog
      and rabbit ventricular muscles, carbachol partially inhibited the positive
      inotropic effect of SCH00013. SCH00013 did not affect the positive inotropic
      effect of isoproterenol at 3 x 10(-6) M, but enhanced it at 3 x 10(-5) M. These
      results indicate that SCH00013 is a cardiotonic agent that primarily acts via an
      increase in myofibrillar Ca++ sensitivity with a moderate contribution of the
      cAMP-dependent mechanism at higher concentrations. SCH00013 has no chronotropic
      activity. The pharmacological profile of SCH00013 implies that the compound may
      be a promising cardiotonic agent for the treatment of congestive heart failure.

PMID- 9765341
TI  - Modulation by angiotensin II of isoproterenol-induced cAMP production in
      preglomerular microvascular smooth muscle cells from normotensive and genetically
      hypertensive rats.
AB  - The objectives of the present study were to determine whether angiotensin II (Ang
      II) modifies beta-adrenoceptor-induced cAMP production in preglomerular
      microvascular smooth muscle cells (PMVSMCs), to determine whether the Ang II/beta
      adrenoceptor interaction on cAMP production differs in PMVSMCs from normotensive
      Wistar-Kyoto (WKY) rats vs. PMVSMCs from spontaneously hypertensive rats (SHR),
      and to elucidate the mechanism of Ang II/beta-adrenoceptor interactions on cAMP
      production in PMVSMCs. In cultured PMVSMCs, isoproterenol increased cAMP levels
      and this effect was markedly enhanced by Ang II. The Ang II enhancement of
      isoproterenol-induced cAMP was significantly greater in SHR PMVSMCs compared with
      WKY PMVSMCs. Neither inhibition of calcineurin with FK506, inhibition of calcium
      calmodulin with W-7 and calmidazolium, nor inhibition of Gi proteins with
      pertussis toxin attenuated Ang II enhancement of isoproterenol-induced cAMP in
      PMVSMCs from either SHR or WKY rats. Moreover, the effect of Ang II on
      isoproterenol-induced cAMP was not mimicked by alpha-2 adrenoceptor stimulation.
      In contrast, chelation of intracellular calcium with BAPTA-AM attenuated,
      increasing intracellular calcium with A23187 augmented, and inhibition of protein
      kinase C with either calphostin C or chelerythrine chloride abolished Ang II
      enhancement of isoproterenol-induced cAMP. We conclude that in cultured PMVSMCs
      Ang II enhances the cAMP response to beta-adrenoceptor agonists via a mechanism
      that involves coincident activation of adenylyl cyclase by stimulatory G proteins
      and protein kinase C. Thus, protein kinase C-mediated activation of adenylyl
      cyclase may attenuate Ang II-induced vasoconstriction in the renal
      microcirculation by raising the intracellular levels of cAMP, and this mechanism
      may be augmented in genetic hypertension.

PMID- 9765342
TI  - Blockade of N- and P/Q-type calcium channels reduces the secondary heat
      hyperalgesia induced by acute inflammation.
AB  - High voltage calcium channels are implicated in nociceptive transmission after
      nerve injury, capsaicin or formalin injection. The purpose of this study was to
      investigate the role of calcium channels in secondary heat hyperalgesia
      associated with acute joint inflammation. After induction of acute inflammation
      (knee joint injection of kaolin and carrageenan), decreased paw withdrawal
      latency (PWL) to radiant heat (i.e., secondary heat hyperalgesia), increased
      guarding of the limb and increased joint circumference occurs. Spinal
      administration (through a microdialysis fiber placed in dorsal horn) of an N-type
      calcium channel blocker (MVIIA, SNX 111, ziconotide, 0.001-0.1 mM), before
      induction of inflammation, prevents the decrease in PWL. Treatment with SNX 111 4
      hr after inflammation reverses heat hyperalgesia. A small reduction in
      spontaneous pain-related behaviors (guarding of the limb) occurs after pre- or
      post-treatment with SNX 111. Spinal blockade of P/Q-type calcium channels (with
      omega-agatoxin IVA) had no effect on the decrease in PWL to radiant heat when
      administered after induction of inflammation. However, pre-treatment with omega
      agatoxin IVA prevents secondary heat hyperalgesia. omega-Agatoxin IVA has no
      effect on spontaneous pain-related behaviors whether administered before or after
      induction of inflammation. In contrast, pre or post-treatment with nifedipine (L
      type calcium channel blocker, 0.01-1.0 mM), had no effect on heat hyperalgesia or
      spontaneous pain-related behaviors induced by acute inflammation. There were no
      differences in joint circumference between groups with any treatment. Thus, N
      type calcium channels contribute to both the development and maintenance of
      secondary heat hyperalgesia while P-type calcium channels are only involved
      during development of hyperalgesia.

PMID- 9765343
TI  - Renal excretory responses produced by the delta opioid agonist, BW373U86, in
      conscious rats.
AB  - Studies were performed in conscious Sprague-Dawley rats to characterize the
      changes in renal excretory function produced by activation of delta opioid
      systems. The intravenous infusion of 50 microgram/kg/min, BW373U86 (BW), a
      nonpeptide delta opioid receptor agonist, produced a significant increase in
      urine flow rate and urinary sodium excretion. The infusion of BW at a dose of 30
      microgram/kg/min produced diuresis without affecting urinary sodium excretion. In
      contrast, BW did not alter either renal excretory parameter at a dose of 10
      microgram/kg/min. The renal responses produced by BW occurred without changes in
      heart rate or mean arterial blood pressure. The diuretic and natriuretic
      responses produced by the i.v. infusion of BW (50 microgram/kg/min) were
      prevented by pretreatment of animals with the selective delta opioid receptor
      antagonist, naltrindole (1 mg/kg, i.v.). When administered alone, naltrindole (1
      mg/kg, i.v.) failed to change any systemic cardiovascular or renal excretory
      parameter. In other groups of animals, the peripheral administration of the delta
      opioid receptor agonist, SNC80, also evoked a profound diuretic and natriuretic
      response (naltrindole sensitive) similar to that produced by BW. In contrast to
      these findings, the diuretic and natriuretic response produced by BW infusion (30
      or 50 microgram/kg/min, i.v.) was abolished in rats having undergone chronic
      bilateral renal denervation. Together, these results demonstrate that the
      peripheral administration of BW373U86 or SNC80 produce marked diuretic and
      natriuretic responses in conscious Sprague-Dawley rats via a delta opioid
      receptor pathway and that intact renal nerves are required for mediating these
      responses. Although endogenous delta opioid systems do not appear to exert a
      tonic influence under basal conditions, these findings suggest that delta opioid
      pathways may evoke significant changes in renal excretory function under
      conditions in which these systems are activated.

PMID- 9765344
TI  - Effects of ketoconazole on the intestinal metabolism, transport and oral
      bioavailability of K02, a novel vinylsulfone peptidomimetic cysteine protease
      inhibitor and a P450 3A, P-glycoprotein dual substrate, in male Sprague-Dawley
      rats.
AB  - We investigated the effects of ketoconazole on the oral bioavailability of
      morpholine-urea-phenylalanine-homophenylalanine-vinylsulfone-phenyl (K02), a
      vinylsulfone peptidomimetic cysteine protease inhibitor, and a P450 3A (CYP3A)
      and P-glycoprotein dual substrate, in male Sprague-Dawley rats, so as to evaluate
      the roles of CYP3A and P-gp in K02 disposition. Male Sprague-Dawley rats (8-10 wk
      old, n = 3-6) were administered a single dose of K02 (10 mg/kg) i.v. or (30
      mg/kg) p.o. with or without a concomitant oral dose of ketoconazole (20 mg/kg).
      Blood samples were collected from 2 min to 8 h after administration through a
      implanted jugular vein cannula. K02 plasma concentrations were determined by
      liquid chromatography/mass spectrometer/mass spectrometer analysis. Ketoconazole
      markedly raised the area under the curve of orally administered K02 from 9.4 +/-
      4.4 to 102 +/- 24 mg . min/liter and decreased K02 oral plasma clearance from
      3810 +/- 1620 to 306 +/- 60 ml/min/kg. With concomitant ketoconazole dosing, the
      changes of AUC of i.v. administered K02 (from 94 +/- 17 to 107 +/- 14 mg .
      min/liter) and clearance (from 110 +/- 22 to 95 +/- 13 ml/min/kg) were not
      significant, although K02 oral bioavailability increased from 2.9 +/- 1.4 to 31.0
      +/- 7.5% (P < .001). In summary, ketoconazole, a dual inhibitor of CYP3A and P
      glycoprotein, can effectively increase K02 oral bioavailability by inhibiting the
      CYP3A/P-gp absorption barrier in the small intestine.

PMID- 9765345
TI  - Characterization of cembranoid interaction with the nicotinic acetylcholine
      receptor.
AB  - The class of diterpenoids with a 14-carbon cembrane ring, the cembranoids,
      includes both competitive and noncompetitive inhibitors of the nicotinic
      acetylcholine receptor (AChR). All 20 coelenterate-derived cembranoids studied in
      this report inhibited [piperidyl-3,4-3H]-phencyclidine ([3H]-PCP) binding to its
      high-affinity site on the electric organ AChR, with IC50s ranging from 0.9 microM
      for methylpseudoplexaurate to 372 microM for lophotoxin. Inhibition was complete
      with all cembranoids but lophotoxin and most Hill coefficients were close to 1.
      Methylpseudoplexaurate and [3H]-PCP binding was competitive.
      Methylpseudoplexaurate and the fourth most potent cembranoid, eunicin, competed
      with each other for [3H]-PCP displacement, indicating that there exist one or
      more cembranoid sites on the AChR. Cembranoid affinity for the AChR correlated
      with hydrophobicity, but was also dependent on other features.
      Methylpseudoplexaurate and n-octanol also competed with each other for [3H]-PCP
      displacement, indicating that the cembranoid site is linked to the n-octanol site
      on the AChR. Unlike lophotoxin, the five cembranoids tested did not inhibit
      [125I]Tyr54-alpha-bungarotoxin binding to the AChR agonist sites. All seven
      cembranoids tested on oocyte-expressed electric organ AChR reversibly blocked
      acetylcholine-induced currents, although the inhibitor concentration curves were
      shallow and the inhibition was incomplete.

PMID- 9765346
TI  - Gamma-hydroxybutyrate is a GABAB receptor agonist that increases a potassium
      conductance in rat ventral tegmental dopamine neurons.
AB  - gamma-Hydroxybutyric acid (GHB) is an abused substance that occurs naturally in
      the basal ganglia. Electrophysiological recordings of membrane voltage and
      current were made to characterize the effects of GHB on dopamine neurons in the
      ventral tegmental area of the rat midbrain slice. Perfusate containing GHB caused
      a concentration-dependent membrane hyperpolarization (EC50 = 0.88 +/- 0.21 mM)
      and a reduction in input resistance (EC50 = 0.74 +/- 0.21 mM). The highest
      concentration of GHB studied (10 mM) hyperpolarized neurons by 20 +/- 3 mV and
      reduced input resistance by 58% +/- 9%. Changes in membrane potential and input
      resistance were blocked by the gamma-aminobutyric acid antagonist CGP-35348 (300
      microM), but neither bicuculline (30 microM) nor strychnine (10 microM) was an
      effective antagonist. Voltage-clamp recordings demonstrated that GHB (1 mM)
      evoked 80 +/- 6 pA of outward current (at -60 mV) that reversed at -110 mV (in
      2.5 mM K+). Increasing concentrations of extracellular K+ progressively shifted
      the reversal to more depolarized potentials. In tetrodotoxin (0.3 microM) and
      tetraethylammonium (10 mM), depolarizing voltage steps (to -30 mV) evoked calcium
      dependent current spikes that were completely blocked by GHB (1 mM). These data
      suggest that GHB is an agonist at gamma-aminobutyric acid receptors and would be
      expected to inhibit DA release by causing K+-dependent membrane
      hyperpolarization.

PMID- 9765347
TI  - F 11440, a potent, selective, high efficacy 5-HT1A receptor agonist with marked
      anxiolytic and antidepressant potential.
AB  - F 11440 (4-methyl-2-[4-(4-(pyrimidin-2-yl)-piperazino)-butyl]-2H, 4H-1,2,4
      triazin-3,5-dione) was the outcome of a research effort guided by the hypothesis
      that the magnitude of the intrinsic activity of agonists at 5-HT1A receptors
      determines the magnitude of their antidepressant and anxiolytic-like effects. The
      affinity of F 11440 for 5-HT1A binding sites (pKi, 8.33) was higher than that of
      buspirone (pKi, 7.50), and somewhat lower than that of flesinoxan (pKi, 8.91). In
      vivo, F 11440 was 4- to 20-fold more potent than flesinoxan, and 30- to 60-fold
      more potent than buspirone, in exerting 5-HT1A agonist activity at pre- and
      postsynaptic receptors in rats (measured by, for example, its ability to decrease
      hippocampal extracellular serotonin (5-HT) levels and to increase plasma
      corticosterone levels, respectively). F 11440 did not have detectable
      antidopaminergic activity (unlike buspirone, which inhibited all of the directly
      observable behavioral effects of methylphenidate in rats), showed no evidence of
      antihistaminergic activity (unlike flesinoxan, which protected against the
      effects of a histamine aerosol in guinea pigs), and had a 70-fold separation
      between its 5-HT1A agonist and alpha-1 adrenergic antagonist properties (measured
      as the ability to inhibit the methoxamineinduced increase in blood pressure in
      rats), unlike flesinoxan, which showed a <3-fold separation. In HeLa cells
      expressing human 5-HT1A receptors, F 11440 decreased the forskolin-induced
      increase in AMP, and, based on its maximal effect, was found to have an intrinsic
      activity of 1.0 relative to that of 5-HT, which was significantly higher than
      that of buspirone (0.49), ipsapirone (0.46) and flesinoxan (0.93). Consistent
      with the aforementioned hypothesis, F 11440 produced anxiolytic- and
      antidepressant-like effects in animal models (i.e., increased punished responding
      in a pigeon conflict procedure and decreased immobility in a rat forced swimming
      test, respectively) that were more substantial than those of buspirone,
      ipsapirone and flesinoxan. Thus, F 11440, shown here to be a potent, selective,
      high efficacy 5-HT1A receptor agonist, appears to have the potential to exert
      marked anxiolytic and antidepressant activity in humans.

PMID- 9765348
TI  - Contribution of the opioid system to alcohol aversion and alcohol drinking
      behavior.
AB  - The effect of blocking delta opioid receptors on alcohol aversion was examined in
      female alcohol-preferring (P) rats using a conditioned taste aversion (CTA)
      paradigm. In experiment 1, alcohol naive P rats were given i.p injections of 0.5,
      1.0 or 1.5 g alcohol/kg BW or saline, paired with consumption of a banana
      flavored solution during 5 conditioning trials. Alcohol in a dose of 0.5 g/kg was
      not aversive while the two higher doses (1.0 and 1.5 g/kg) were both aversive in
      the CTA paradigm. In experiment 2, the effect of the selective delta opioid
      receptor antagonist, naltrindole (NTI), on alcohol aversion was examined. Rats
      were pretreated with NTI in doses of 2.5, 5.0, 10.0 or 20.0 mg/kg before
      conditioning using the nonaversive dose of alcohol from Experiment 1. As in
      experiment 1, the 0.5 g/kg dose of alcohol did not produce a CTA. Administration
      of NTI alone in doses of 2.5, 5.0 or 10.0 mg/kg did not produce a CTA. However,
      when the nonaversive dose of alcohol (0.5 g/kg) was combined with NTI in a dose
      of either 5.0 or 10.0 mg/kg, an aversion to alcohol was seen. The highest dose of
      NTI (20 mg/kg) produced a CTA when given either alone and in combination with
      alcohol. The results indicate that blocking the action of opioid peptides at the
      delta opioid receptor can make a nonaversive dose of alcohol aversive which
      suggests that opioid peptides, acting via the delta opioid receptor, play an
      important role in regulating alcohol aversion.

PMID- 9765349
TI  - Blockage by terfenadine of the adenosine triphosphate (ATP)-sensitive K+ current
      in rabbit ventricular myocytes.
AB  - We examined the blocking effects of terfenadine, an antihistaminic agent, on the
      ATP-sensitive K+ current (IK,ATP) in rabbit ventricular cells. IK,ATP was induced
      by cromakalim or NaCN. Terfenadine blocked the IK,ATP with an IC50 of 1.7 microM
      at -10 mV. This blockage was voltage dependent; depolarization induced a stronger
      blockage. According to the transmembrane electrical field model, terfenadine
      interacts with the site located 15 to 18% from the cytoplasmic membrane surface.
      In line with the assumption that the binding site is near the cytoplasmic
      surface, terfenadine applied to the cytoplasmic solution potently inhibited the
      single-channel activity for IK,ATP in the inside-out configuration (IC50 0.19
      microM). In contrast, terfenadine applied to the external solution did not affect
      the channel activity in the cell-attached configuration, but inhibited it when
      applied into the pipette. The inhibition of the single channels by terfenadine
      was accompanied by flickering of the channels. These findings suggest that 1)
      terfenadine blocks the ATP-sensitive K+ channel in the open state, 2) the binding
      site is near the internal membrane surface and 3) terfenadine is poorly
      diffusible into the lipid biomembrane and accesses the binding site via the
      hydrophilic pathway. Terfenadine also inhibited the transient outward K+ current,
      inward rectifier K+ current and E4031-sensitive rectifier K+ current. However,
      the inhibition of these repolarization currents by terfenadine at 1 microM was
      not sufficient to prolong the action potential duration significantly. Whereas,
      terfenadine (1 microM) prolonged the action potential duration which had been
      shortened by cromakalim. Terfenadine may modify the ischemia-induced arrhythmias
      by blocking IK,ATP.

PMID- 9765350
TI  - Effects of novel anti-inflammatory compounds on healing of acetic acid-induced
      gastric ulcer in rats.
AB  - Nonsteroidal anti-inflammatory drugs often cause development of significant GI
      lesions. Selective inhibitors of prostaglandin G/H synthase/cyclooxygenase-2
      (PGHS-2) enzyme and some dual inhibitors of PGHS/5-lipoxygenase (5-LO) enzymes
      have been reported to be potent anti-inflammatory compounds that carry a much
      lower risk of having GI irritating effects. We have evaluated the anti
      inflammatory effect and the GI safety profile of three new anti-inflammatory
      compounds: the selective PGHS-2 inhibitors NS-398 and PD 138387 and the PGHS/5-LO
      dual inhibitor PD 137968. All the compounds tested showed an anti-inflammatory
      activity in the carragenan footpad edema test in rats. None of these compounds
      caused either gastric damage 4 h after p.o. administration of 100 mg/kg in rats
      or inhibition of PGE2 synthesis in the stomach. However, when administered p.o.
      at an effective anti-inflammatory dose to rats with pre-existing acetic acid
      induced gastric ulcer, NS-398 caused a statistically significant delay of ulcer
      healing. No impairment of the ulcer healing was observed with the other compounds
      evaluated. Derivatives of 2,6-di-tert-butylphenol, whose members may act as PGHS
      1/PGHS-2 inhibitors, selective PGHS-2 inhibitors or PGHS/5-LO dual inhibitors,
      are novel anti-inflammatory compounds that are devoid of GI irritating effects
      and do not affect the rate of pre-existing gastric ulcer healing.

PMID- 9765351
TI  - A neurotensin receptor antagonist inhibits acute immobilization stress-induced
      cardiac mast cell degranulation, a corticotropin-releasing hormone-dependent
      process.
AB  - Stress worsens certain disorders such as migraines or asthma, and has also been
      implicated in sudden myocardial arrest. It was previously shown that acute
      psychological stress by immobilization results in dura mast cell degranulation,
      an effect blocked by pretreatment with antiserum against corticotropin-releasing
      hormone (CRH). Moreover, CRH was recently shown to induce skin mast cell
      degranulation. The effect of psychological stress was investigated on rat cardiac
      mast cells, because their release of coronary constrictive and proinflammatory
      molecules contributes to myocardial ischemia and possibly arrhythmias.
      Immobilization of rats for 30 min induced maximal cardiac mast cell degranulation
      as evidenced by light and electron microscopy. This effect was inhibited by
      pretreatment with the "antiallergic" drug sodium cromoglycate (cromolyn), which
      is thought to act primarily through mast cell stabilization. Mast cell
      degranulation was also blocked by preincubation with antiserum against CRH and
      was partially inhibited by a CRH type-1 receptor selective antagonist. Sensory
      neuropeptides did not appear to influence this effect, but a nonpeptide
      neurotensin receptor antagonist blocked stress-induced cardiac mast cell
      degranulation. This finding supports the involvement of neuropeptide neurotensin
      which is present in the heart and is known to trigger mast cell degranulation.
      These results indicate acute stress could result in local CRH and nonpeptide
      neurotensin release which could contribute to myocardial pathophysiology through
      direct or indirect release of cardiac mast cell mediators.

PMID- 9765352
TI  - The antiproliferative and cell cycle effects of 5,6,7, 8-tetrahydro-N5,N10
      carbonylfolic acid, an inhibitor of methylenetetrahydrofolate dehydrogenase, are
      potentiated by hypoxanthine.
AB  - 5,6,7,8-Tetrahydro-N5,N10-carbonylfolic acid (LY354899) has been demonstrated to
      inhibit the dehydrogenase activity of C1-tetrahydrofolate synthase. This compound
      was only moderately antiproliferative toward CCRF-CEM lymphocytic leukemia cells
      in culture, but induced apoptosis after long incubation times. Slightly greater
      potency was observed in CEM cells adapted to grow in low folate media. Cell cycle
      alterations induced by LY354899 were unique relative to antifolates that inhibit
      either the purine or thymidine de novo biosynthetic pathways. Based on the
      observed changes in DNA content, we hypothesized that inhibition of the
      dehydrogenase resulted in two temporally distinct events: the first was a
      purineless-like effect and the second was a thymineless-like effect that resulted
      in apoptosis. To test this hypothesis, we combined LY354899 with the purine
      salvage metabolite, hypoxanthine. This combination resulted in an earlier and
      more dramatic apoptotic response, indicating that the thymineless effect had been
      potentiated. Biochemical analysis of ribo- and deoxyribonucleoside triphosphates
      confirmed that inhibition of the dehydrogenase activity initially resulted in
      decreased pools of deoxypurines and deoxypyrimidines, followed 16 hr later by an
      increase in deoxyadenosine triphosphate (dATP) and a further decrease in
      deoxythymidine triphosphate (dTTP). These studies demonstrate that the inhibition
      of the dehydrogenase activity of C1-tetrahydrofolate synthase may represent a
      viable target for the development of novel antifolates. The results are discussed
      in terms of deoxypurine and deoxypyrimidine biosynthesis.

PMID- 9765353
TI  - Delta opioid peptide [D-Ala2,D-leu5]enkephalin blocks the long-term loss of
      dopamine transporters induced by multiple administrations of methamphetamine:
      involvement of opioid receptors and reactive oxygen species.
AB  - Delta opioid peptide [D-Ala2,D-leu5]enkephalin (DADLE) can prolong organ
      preservation and increases myocardial tolerance to ischemia. Our study examined
      the protective property of DADLE against methamphetamine- (METH) induced
      dopaminergic terminal damage in the central nervous system. Because the
      neurotoxicity of METH involves reactive oxygen species, we also examined if DADLE
      might be an antioxidative agent in vitro. DADLE at 2 and 4 mg/kg (i.p.), given 30
      min before each METH administration (5 or 10 mg/kg, i.p., four injections in a
      day at 2-hr intervals), dose-dependently blocked the METH-induced long-term
      dopamine transporter loss. The opioid antagonist naltrexone blocked this action
      of DADLE in both aspects of striata but tends not to affect the effects of DADLE
      in the nucleus accumbens. DADLE did not alter changes in body temperature induced
      by METH. The reduction of striatal dopaminergic content and tyrosine hydroxylase
      activity caused by METH, however, were not blocked by DADLE. In vitro, DADLE was
      approximately equipotent to glutathione in inhibiting both superoxide anion
      formation induced by xanthine oxidase and hydroxyl radical formation evoked by
      ferrous/citrate complex. DADLE was only slightly less potent than glutathione in
      inhibiting the iron/ascorbate-induced brain lipid peroxidation. These results
      suggest that DADLE can protect the terminal membranes of dopaminergic neurons
      against METH-induced insult but not the loss of dopaminergic content and tyrosine
      hydroxylase activity and that this action of DADLE might involve opioid receptors
      as well as the sequestration of free radical.

PMID- 9765354
TI  - Differential effects of S6 mutations on binding of quinidine and 4-aminopyridine
      to rat isoform of Kv1.4: common site but different factors in determining
      blockers' binding affinity.
AB  - Quinidine and 4AP are two nonspecific K channel blockers. Both block voltage
      gated K channels from the intracellular side of the membrane and, in most cases,
      binding is facilitated by channel activation. However, there are distinct
      differences between quinidine and 4AP in the time- and voltage-dependencies of
      drug-channel interaction. To learn about the molecular basis underlying the
      similarities as well as differences in drug actions between quinidine and 4AP, we
      used rKv1.4 (rat isoform of Kv1.4) as a model and studied: 1) Is there an overlap
      between the binding sites of quinidine and 4AP? and 2) What factors are involved
      in determining the binding affinity and kinetics of drug-channel interaction? Our
      data show that mutations at a position in the S6 domain of rKv1.4 (position 529)
      can cause dramatic and often opposite effects on quinidine and 4AP binding. For
      quinidine, the degree of steric hindrance imposed by side chain at position 529
      is an important factor in determining binding affinity. For 4AP, 529 mutations
      that slow the rate of deactivation reduce binding affinity, probably due to a low
      binding affinity in the open state. This, in conjunction with the observations
      that 4AP binding is facilitated by channel activation, suggests that optimal 4AP
      binding may occur in a transitional state between fully-closed and fully-open
      states. In addition, hydrophobic interactions between blocker molecules and
      residues at 529 tend to stabilize the binding of both quinidine and 4AP. Because
      the S6 amino acid sequences are well conserved among many voltage-gated K
      channels, our findings have general implications in understanding the structural
      determinants of quinidine and 4AP binding to different K channels.

PMID- 9765355
TI  - Protection from cadmium cytotoxicity by N-acetylcysteine in LLC-PK1 cells.
AB  - N-acetylcysteine (NAC) has been known not only to stimulate synthesis of
      glutathione but also to affect the gene regulation. In our study, effects of NAC
      on the cytotoxicity of cadmium (Cd) were examined in LLC-PK1 cells. Preincubation
      and subsequent incubation with 1 mM NAC almost completely suppressed Cd-induced
      cellular damage evaluated either by trypan blue exclusion or lactate
      dehydrogenase leakage. This almost complete protection required the presence of
      NAC during Cd exposure. Treatment with 1 mM NAC increased the intracellular
      glutathione level approximately 2-fold. Inhibition of this increase by buthionine
      sulfoximine did not abolish the protection by NAC. One mM NAC also suppressed Cd
      induced increase of c-Fos protein although NAC alone did not change the protein
      content. The inhibition of transcriptions by actinomycin D did not affect the
      protection by NAC. Thus, NAC-induced protection appeared to be independent of
      glutathione level or the transcriptional activation of genes including c-fos.
      However, treatment with NAC markedly lowered the uptake of Cd into cells although
      it did not affect the efflux clearly. Addition of NAC during the exposure to Cd
      suppressed Cd-induced cellular damage but the suppression decreased when the
      duration of the exposure without NAC increased. These results suggest that NAC
      induced protection against Cd cytotoxicity is mainly due to the lowered uptake of
      Cd into the cells.

PMID- 9765356
TI  - Down-regulation of the expression of three major rat liver cytochrome P450S by
      endotoxin in vivo occurs independently of nitric oxide production.
AB  - Endotoxemia results in both the down-regulation of multiple cytochrome P450 genes
      and the induction of inducible nitric oxide synthase (NOS2). The nitric oxide
      (NO) released during inflammation has been implicated as the mediator of the
      decreased catalytic activity and expression of several cytochrome P450 isozymes.
      We examined the role of NO in the decreases of both gene expression and activity
      of three major P450s in the endotoxemic Fischer 344 rat. Endotoxin (LPS)
      treatment suppressed both mRNA and protein expression of P450 2C11, 2E1, and 3A2.
      Coadministration of the NOS inhibitor aminoguanidine to LPS-treated rats
      completely inhibited the release of NO into the plasma but did not reverse the
      down-regulation of expression of any of the P450s examined at three time points.
      LPS treatment had a biphasic effect on some P450 catalytic activities. The
      hydroxylation of testosterone at the 2alpha-, 16alpha- and to a lesser extent
      6beta-positions, was inhibited 6 hr after LPS treatment and returned to normal by
      12 hr. The role of NO in the 6 hr effects could not be assessed due to effects of
      the aminoguanidine treatment itself. The second phase of decreased P450
      activities seen after 24 hr was attributed to the NO-independent decrease in gene
      expression. Our results suggest that NO is not required for the LPS-evoked down
      regulation of P450 2C11, 2E1 and 3A2 mRNA or protein expression. We cannot rule
      out a possible role for NO in the decreases in P450 activities seen early in the
      response.

PMID- 9765357
TI  - Differential effect of ethanol on PC12 cell death.
AB  - Our goal was to examine the effects of ethanol on cell death using rat
      pheochromocytoma (PC12) cells as a neuronal model. Withdrawal of serum for 24 hr
      increased the number of PC12 cells labeled with ethidium homodimer indicating an
      increase in cell death. Inclusion of 50 mM ethanol during the serum deprivation
      further increased the amount of ethidium fluorescence by 39%. Although reducing
      the serum concentration from the usual 15 to 4% did not alter cellular viability,
      a significant increase in the amount of ethidium fluorescence was observed in
      PC12 cells incubated for 24 hr in the presence of 4% serum and 150 mM ethanol. No
      change in viability was observed in cells exposed to either 150 mM ethanol in the
      presence of 15% serum or 50 mM ethanol in the presence of 4% serum. Inclusion of
      ethanol during serum deprivation increased the amount of soluble DNA found in the
      15,000 x g supernatant. Similarly, using the terminal deoxynucleotidyl
      transferase dUTP nick-end labeling method to visualize DNA fragmentation in situ,
      ethanol caused a 213% increase in the number of PC12 cells labeled during serum
      withdrawal. Agarose gel electrophoresis of the DNA isolated from cells maintained
      in the absence of serum yielded the classical DNA laddering pattern of 180 to 200
      bp fragments suggestive of apoptosis. Ethanol caused a concentration-dependent
      increase in the amount of DNA laddering in cells deprived of serum. Furthermore,
      ethanol significantly potentiated the DNA laddering of cells maintained in 4%
      serum. In contrast to the ethanol-induced increase in cell death when serum
      factors were reduced or withdrawn, 150 mM ethanol lowered by 34% the number of
      ethidium-labeled PC12 cells observed after a 30-min exposure to 2 mM H2O2.
      Similarly, agarose gel electrophoresis of the DNA from H2O2-treated cells did not
      display DNA laddering. This study demonstrates that: 1) ethanol antagonizes the
      trophic action of serum factors; 2) pharmacologically relevant ethanol
      concentrations significantly potentiate apoptosis after serum withdrawal and 3)
      this enhancement appears specific for apoptosis.

PMID- 9765358
TI  - Pharmacology and intracellular signaling mechanisms of the native human orphan
      receptor BRS-3 in lung cancer cells.
AB  - Neither the native ligand nor the cell biology of the bombesin (Bn)-related
      orphan receptor subtype 3 (BRS-3) is known. In this study, we used RT-PCR to
      identify two human lung cancer lines that contain sufficient numbers of native
      hBRS-3 to allow study: NCI-N417 and NCI-H720. In both cell lines,
      [DPhe6,betaAla11,Phe13, Nle14]Bn(6-14) stimulates [3H]inositol phosphate. In NCI
      N417 cells, binding of 125I-[DTyr6,betaAla11,Phe13,Nle14]Bn(6-14) was saturable
      and high-affinity. [DPhe6,betaAla11,Phe13,Nle14]Bn(6-14) stimulated phospholipase
      D activity and a concentration-dependent release of [3H]inositol phosphate (EC50
      = 25 nM) and intracellular calcium (EC50 = 14 nM); the increases in intracellular
      calcium were primarily from intracellular stores. hBRS-3 activation was not
      coupled to changes in adenylate cyclase activity, [3H]-thymidine incorporation or
      cell proliferation. No naturally occurring Bn-related peptides bound or activated
      the hBRS-3 with high affinity. Four different bombesin receptor antagonists
      inhibited increases in [3H]inositol phosphate. Using cytosensor microphysiometry,
      we found that [DPhe6,betaAla11,Phe13, Nle14]Bn(6-14) caused concentration
      dependent acidification. The results show that native hBRS-3 receptors couple to
      phospholipases C and D but not to adenylate cyclase and that they stimulate
      mobilization of intracellular calcium and increase metabolism but not growth. The
      discovery of human cell lines with native, functional BRS-3 receptors, of new
      leads for a more hBRS-3-specific antagonist and of the validity of
      microphysiometry as an assay has yielded important tools that can be used for the
      identification of a native ligand for hBRS-3 and for the characterization of BRS
      3-mediated biological responses.

PMID- 9765359
TI  - Microsomal metabolism of delavirdine: evidence for mechanism-based inactivation
      of human cytochrome P450 3A.
AB  - Administration of delavirdine, an HIV-1 reverse transcriptase inhibitor, to rats
      or monkeys resulted in apparent loss of hepatic microsomal CYP3A and delavirdine
      desalkylation activity. Human CYP3A catalyzes the formation of desalkyl
      delavirdine and 6'-hydroxy delavirdine, an unstable metabolite, while CYP2D6
      catalyzes only desalkyl delavirdine. CYP2D6 catalyzed desalkyl delavirdine
      formation was linear with time (up to 30 min) but when catalyzed by cDNA
      expressed CYP3A4 or human liver microsomes the reaction rate declined
      progressively with time. Coincubation with triazolam showed that delavirdine
      caused a time- and NADPH-dependent loss of CYP3A4 activity in human liver
      microsomes as measured by triazolam 1'-hydroxylation. The catalytic activity loss
      was saturable and was characterized by a Ki of 21.6 +/- 8.9 microM and a kinact
      of 0.59 +/- 0.08 min-1. An apparent partition ratio of 41 was determined with
      cDNA expressed CYP3A4, based on the substrate depletion method. Incubation of
      [14C]delavirdine with microsomes from several species resulted in irreversible
      association with an approximately 50 kDa protein, as demonstrated by SDS
      PAGE/autoradiography. Binding to the protein was NADPH dependent, glutathione
      insensitive, proportional to the level of CYP3A expression and was inhibited by
      ketoconazole, a specific CYP3A inhibitor. NADPH-dependent irreversible binding to
      human and rat total microsomal protein was demonstrated following exhaustive
      extraction of microsomal protein. Binding was decreased in the presence of
      glutathione and appeared to be related to expression level of CYP3A. These
      results suggest that delavirdine can inactivate CYP3A and has the potential to
      slow the metabolism of coadministered CYP3A substrates.

PMID- 9765360
TI  - Oxytocin inhibits the uptake of serotonin into uterine mast cells.
AB  - The uptake of serotonin (5HT) into mouse uterine horns, the localization of sites
      at which this amine could be stored and the effect of oxytocin on 5HT uptake were
      studied. To analyze the characteristics of the 5HT uptake process, the tissue was
      incubated with [3H]serotonin. The uptake of [3H]5HT was Na+ dependent and
      saturable (Kmapp: 166 +/- 15 nM, Vmax: 404 +/- 25 fmol/mg tissue, 30 min
      (diestrous); and Km: 165 +/- 39 nM, Vmax: 276 +/- 43 fmol/mg tissue, 30 min
      (estrous), n = 6), and was inhibited by imipramine, fluoxetine and 6
      nitroquipazine (IC50: 2; 0.09 and 0.5 nM, respectively). In the myometrium the
      main 5HT uptake process was localized in uterine mast cells. This was determined
      by treating the uterine horns with 6-hydroxydopamine, by using an
      immunocytochemical approach and by studying the outflow of 3H under the action of
      stimuli directed to either mast cells (compound 48/80: 10 microgram/ml) or
      sympathetic nerves (high K+: 100 mM and veratridine: 20 microM) in uterine
      preparations. Oxytocin inhibited [3H]5HT uptake into uterine mast cells during
      estrus, but not in ovarectomized mice treated with progesterone. Maximal
      inhibition was attained at 0.03 nM, with a significant reduction in both Kmapp
      and Vmax (87 +/- 15 nM and 184 +/- 36 fmol/mg tissue/30 min, n = 3,
      respectively). This effect was reversed by the addition of OVT16, an oxytocin
      antagonist, at a concentration of 4 nM (Kmapp 158 +/- 35 nM, Vmax: 278 +/- 24
      fmol/mg tissue, 30 min, n = 3). These findings support a new potential role of
      oxytocin and mast cells as a local regulators of serotonin bioavailability in
      myometrium. Because serotonin is recognized as an important endogenous uterotonic
      compound, this effect could be considered as an indirect action of oxytocin that
      may contribute to its potency as a labor inducer after genomic effects of
      estrogens are expressed in uterine tissue.

PMID- 9765361
TI  - Absorption enhancement, structural changes in tight junctions and cytotoxicity
      caused by palmitoyl carnitine in Caco-2 and IEC-18 cells.
AB  - Palmitoyl carnitine chloride (PCC) has been shown to be an effective enhancer of
      intestinal transport of hydrophilic molecules. The exact mechanism by which the
      epithelial barrier function is decreased is not clear. In an attempt to elucidate
      the mechanism of action of PCC, we studied the relationship among absorption
      enhancement, cell viability and tight junction protein localization in the human
      colonic Caco-2 cell line and the rat small intestinal cell line IEC-18. Filter
      grown cells were exposed to 0 to 1 mM PCC for 30 min, and the efficacy of PCC
      treatment was determined by assessing the transepithelial electrical resistance
      and the apparent permeability for mannitol and PEG-4000. Membrane lysis and
      cytotoxicity were assessed by measurement of lactate dehydrogenase leakage and
      uptake of propidium iodide and neutral red. The immunolocalization of the tight
      junctional protein ZO-1 was quantified using CSLM and image-processing software.
      In both cell lines, PCC caused a dose-dependent decrease in transepithelial
      electrical resistance and a concomitant increase in the permeability for mannitol
      and PEG-4000. The transport enhancement was accompanied by an increase in apical
      membrane permeability and a reduction in cell viability. At higher PCC
      concentrations (>/=0.4 mM), the distribution of the tight junctional protein ZO-1
      was changed and cells were unable to recover viability. PCC is effective as an
      absorption enhancer for hydrophilic macromolecules. However, lytic effects on the
      cell membrane and reduced cell viability were concomitant with transport
      enhancement.

PMID- 9765362
TI  - Participation of nitric oxide in the mucosal injury of rat intestine induced by
      ischemia-reperfusion.
AB  - The dual role of nitric oxide as a cytoprotective or a cytotoxic free radical gas
      has been noted in various types of pathophysiological conditions, including the
      digestive system. The aim of this study was to examine the role of nitric oxide
      in the mucosal injury induced by ischemia-reperfusion in the rat small intestine.
      A transient intestinal ischemia was produced in the catheterized ileal segments
      of rats by occluding the anterior mesenteric artery for 60 min. Nitric oxide
      metabolites (NO2- and NO3-) and lactate dehydrogenase activity in perfusates of
      the intestinal lumen were measured over 5 hr periods. The time-course of
      histological changes in small intestine was also observed. After ischemia
      reperfusion, nitric oxide release in the intestinal lumen increased significantly
      and the dynamics of nitric oxide release correlated with that of lactate
      dehydrogenase leakage. The administration of NG-nitro-L-arginine methyl ester
      (1.0-2.5 mg/kg) inhibited this increased nitric oxide release and the lactate
      dehydrogenase leakage and afforded protection against the mucosal injury induced
      by ischemia-reperfusion. In conclusion, the nitric oxide production that was
      accelerated by ischemia-reperfusion of small intestine may possibly participate
      in the breakdown of intestinal mucosa after ischemia-reperfusion insult.

PMID- 9765363
TI  - Targeted delivery of plasmid DNA to hepatocytes in vivo: optimization of the
      pharmacokinetics of plasmid DNA/galactosylated poly(L-lysine) complexes by
      controlling their physicochemical properties.
AB  - In vivo receptor-mediated targeting of plasmid DNA to hepatocytes was achieved
      through optimizing the physicochemical and pharmacokinetic properties of a
      plasmid DNA/carrier complex. Galactosylated poly(L-lysine) (Gal-PLL) was
      synthesized using PLL with a molecular weight of 1,800, 13,000 or 29,000 without
      loss of the cationic charge. Plasmid DNA encoding chloramphenicol
      acetyltransferase was complexed with each Gal-PLL. A larger amount of PLL1800 is
      required for the complex formation than with PLL13000 and PLL29000, and
      increasing the number of galactose units on Gal-PLL resulted in reduced binding
      to plasmid DNA. The particle size and zeta-potential of the complexes varied
      depending on the mixing ratio and Gal-PLL used. Then, plasmid DNA/Gal-PLL
      complexes having diameters of 200 nm or less and a weak negative charge were
      prepared. After i.v. injection of [32P]plasmid DNA/Gal13-PLL13000 and
      [32P]plasmid DNA/Gal26-PLL29000, almost 80% of the radioactivity rapidly
      accumulated in the liver, preferentially in the parenchymal cells. The hepatic
      uptake clearances (CLliver) were much greater than any of the other tissue uptake
      clearances. Compared with these complexes, [32P]plasmid DNA/Gal5-PLL1800 and
      [32P]plasmid DNA/Gal5-PLL13000 had a smaller CLliver, suggesting that both the
      molecular weight of PLL and the degree of galactose modification determine the
      hepatic targeting of plasmid DNA. In vitro and in vivo gene expression studies
      revealed that plasmid DNA/Gal13-PLL13000 and plasmid DNA/Gal26-PLL29000 complexes
      are superior to plasmid DNA/Gal5-PLL1800 complex for introducing DNA into cells.
      These results demonstrated that an optimal design of a DNA/carrier complex based
      on physicochemical properties and a pharmacokinetic analysis of the distribution
      properties leads to successful in vivo gene delivery.

PMID- 9765364
TI  - Characterization and purification of the bovine adrenal angiotensin IV receptor
      (AT4) using [125I]benzoylphenylalanine-angiotensin IV as a specific photolabel.
AB  - The Ang IV receptor, AT4, has been shown to play important roles in various
      mammalian tissues. In this study, structural properties of the AT4 receptor from
      bovine adrenals are described using a novel photoactive analog of Ang IV,
      [125I]Benzoylphenylalanine-Ang IV (BP-Ang IV), recently developed in our
      laboratory. [125I]BP-Ang IV is identical to Ang IV with regards to binding
      specificity and affinity and is easily cross-linked to the AT4 receptor under UV
      light, thus greatly facilitating the structural analysis of the AT4 receptor by
      SDS-PAGE. Comparisons between the native, reduced and nonreduced forms of the AT4
      receptors by SDS-PAGE revealed that this receptor consists of multiple subunits.
      The subunit containing the Ang IV binding site (designated as the alpha subunit)
      has a molecular weight of approximately 165 kDa and contained approximately 20% N
      linked carbohydrates. A subunit similar to the adrenal alpha subunit of the AT4
      receptor was identified in all of the bovine tissues examined. Hippocampus and
      aorta contained additional [125I]BP-Ang IV bound protein bands with molecular
      weights of 150 and 125 kDa, respectively. Further, the alpha subunit was purified
      to homogeneity using a method that integrates electrofractionation with
      conventional protein purification techniques.

PMID- 9765365
TI  - Depletion of protein kinase C-alpha by antisense oligonucleotides alters beta
      adrenergic function and reverses the phorbol ester-induced reduction of
      isoproterenol-induced adenosine 3'-5'-cyclic monophosphate accumulation in murine
      Swiss 3T3 fibroblasts.
AB  - Beta-adrenergic agonists are well known to increase the activity of adenylate
      cyclase, yielding increases of the intracellular concentration of cAMP. It has
      been reported that activation of protein kinase C (PKC) by phorbol esters reduces
      the amplitude of isoproterenol-induced cAMP production in a 3T3-L1 cell line. In
      this study, we investigated whether PKC-alpha is involved in this process in
      murine Swiss 3T3 fibroblasts. A 20-mer phosphorothioate oligonucleotide designed
      to hybridize to the AUG initiation codon of the murine PKC-alpha mRNA, which
      contains 2'-O-methoxyethyl modifications incorporated into the 5' and 3' segments
      of the oligonucleotide, was used to assess the putative role of PKC-alpha in the
      beta-adrenergic receptor regulation. ISIS 14012 reduced PKC-alpha mRNA for over
      72 hr after the initial treatment and the reduction was concentration dependent,
      whereas the mismatch control, ISIS 13818, had no effect. This depletion was found
      to be selective; ISIS 14012 had no effect on the mRNA expression of PKC-delta and
      PKC-zeta. ISIS 14012 reduced in a time and concentration-dependent fashion the
      levels of immunoreactive PKC-alpha protein by over 85% at 72 hr after treatment.
      Depletion of PKC-alpha inhibited the effect of isoproterenol-induced cAMP
      production by phorbol dibutyrate (PdBu). This finding is corroborated by the use
      of a nonspecific inhibitor of PKC, GF-109203x, which also prevented the effect of
      PdBu. Depletion of PKC-alpha by ISIS 14012 potentiated isoproterenol-induced cAMP
      production in cells untreated with PdBu. However, neither depletion of PKC-alpha
      nor PKC activation by a phorbol ester altered beta-adrenergic receptor affinity
      and density. PKC activation by PdBu did not alter forskolin-induced cAMP levels,
      but enhanced cAMP production by cholera toxin. PKC-alpha inhibition by ISIS 14012
      had no effect on either cholera toxin-induced increases in cAMP or the acute
      effects of phorbol esters on cholera toxin in induction of cAMP. Thus, PKC-alpha
      appears to be involved in the regulation of beta-adrenergic receptor coupling to
      adenylate cyclase, possibly by phosphorylating the Gs protein, but other PKC
      isotypes must be involved in the effects observed when cells are treated with
      cholera toxin.

PMID- 9765367
TI  - Obituary 
AB  - Sheila Willmott, (1921-1998)CAB International and the Editor, Assistant Editor
      and Editorial Board of the Journal of Helminthology wish to express their deepest
      sympathy to the family and friends of Sheila Willmott who died on 8 May 1998
      after a very short illness. Sheila served as Editor of the Journal of
      Helminthology from 1980 to 1986.Dr Lotfi Khalil, formerly Deputy Director of the
      International Institute of Parasitology at St Albans, worked closely with Sheila
      and has written the following tribute.John W. Lewis, EditorSheila Willmott was a
      leading contributor to the dissemination of parasitic information before the
      development of computerization and information technology. She was born on 8
      June, 1921, in London, and was educated at Tollington High School for Girls,
      Chelsea Polytechnic and University College, London. She did her PhD at the London
      School of Hygiene and Tropical Medicine under the supervision of Professor John
      Buckley, the subject of her thesis being the study of amphistome digeneans. Her
      studies were interrupted as a result of the Second World War when she was
      'drafted' as a Rodent Instructor at the Ministry of Agriculture, Fisheries and
      Food. After completing her PhD, she was appointed Assistant Lecturer in Zoology
      at the University College of South Wales and Monmouthshire, Cardiff. In 1951,
      Professor R.T. Leiper, the Director of the Bureau of Agricultural Parasitology
      (Helminthology) recruited her as a Scientific Information Officer. She was
      appointed Assistant Director of the Bureau in 1954, and Director in 1961, where
      she stayed until her retirement in 1980.During her period as Director of the
      Bureau, which was sited in the White House in the centre of St Albans, she
      maintained and improved the high quality of Helminthological Abstracts and, in
      1976, accepted the extra burden of starting and producing Protozoological
      Abstracts. In 1979, she initiated and edited a primary journal, Systematic
      Parasitology, devoted to papers on the taxonomy and systematics of parasites,
      published by Junk. The activities of the Bureau were greatly expanded and she
      initiated the taxonomic laboratories to provide a worldwide service for the
      identification of animal helminths and plant-parasitic nematodes and to undertake
      taxonomic research. A vast helminth reference collection was started, and the
      Bureau became a recognized centre for the deposition of type specimens. The
      library of the Bureau accumulated an enormous number of reference books, journals
      and reprints, and provided a photocopying service supplying, at short notice,
      copies of papers and publications. A number of books and other publications,
      including the CIH Keys to the Nematode Parasites of Vertebrates, were produced
      and edited by her and others. She also persuaded the Natural Environment Research
      Council to finance the Fisheries Helminthology Unit which she established at the
      Bureau in 1960, where it remained until it was transferred to Plymouth as part of
      the Institute for Marine Environmental Research. The Bureau's name and status
      were changed to the Commonwealth Institute of Helminthology, Commonwealth
      Institute of Parasitology and, finally, the International Institute of
      Parasitology.As Director, she travelled extensively and visited Commonwealth and
      other countries, where she gave a number of seminars on information services and
      the work of the Institute and the Commonwealth Agricultural Bureaux (CAB) as a
      whole. She encouraged contact with Eastern Europe and visited Poland,
      Czechoslovakia, Hungary, Bulgaria and the USSR. She initiated the system of
      exchange publications with these countries, and this resulted in the exposure of
      the literature from these countries to other research workers when abstracts of
      these papers appeared in Helminthological Abstracts in English. Her links with
      Eastern Europe resulted in her editing three volumes of taxonomic monographs
      produced in English by Czech and Russian scientists. (ABSTRACT TRUNCATED)

PMID- 9765366
TI  - Human vascular endothelial cells express functional nicotinic acetylcholine
      receptors.
AB  - ACh receptors sensitive to nicotine (nAChR) are present in human skin
      keratinocytes and in bronchial epithelial cells. They are stimulated by ACh
      secreted by the same cells that express them, and they modulate cell motility and
      shape. A variety of non-neuronal tissues, including endothelial cells, synthesize
      ACh, which raises the possibility that they are sensitive to nicotine. We
      demonstrate here that endothelial cells that line blood vessels express
      functional nAChRs. Their structure and ion-gating properties are similar to those
      of the nAChRs expressed by ganglionic neurons and by skin keratinocytes and
      bronchial epithelial cells. In situ hybridization experiments using primary
      cultures of endothelial cells from human aorta demonstrated the presence in these
      cells of the subunits believed to contribute to ganglionic ACh receptors (AChRs)
      of the alpha3 subtype: alpha3, alpha5, beta2 and beta4. Binding of radiolabeled
      epibatidine-a high-affinity specific ligand of certain neuronal AChRs, including
      the alpha3 subtypes-revealed the presence of approximately 900 specific binding
      sites per cell. We assessed the presence of functional AChRs by patch-clamp
      experiments. Cultured human endothelial cells express ion channels that are
      opened by (+)-anatoxin-a and are blocked by dihydro-beta-erythroidine. These are
      specific agonist and antagonist, respectively, of neuronal AChRs of the alpha3
      subtype. The ion-gating properties of the endothelial AChRs were similar to those
      of neuronal ganglionic AChRs. The presence of AChRs sensitive to nicotine in
      endothelial cells may be related to the toxic effects of nicotine on the vascular
      system.

PMID- 9765368
TI  - Antibody responses to fluke cysteine proteinases in Paragonimus- and Fasciola
      infected rats.
AB  - IgG and IgM antibody responses to fluke cysteine proteinases in Paragonimus
      ohirai- and Fasciola sp.-infected rats were followed by means of cystatin capture
      ELISA using fluke excretory-secretory products for 10 weeks after infection. The
      specific IgG antibodies were detectable at week 2 postinfection in all P. ohirai
      infected and some Fasciola-infected rats. Levels of specific IgG antibodies
      increased rapidly between week 2 and 6, and slightly thereafter, in both infected
      groups. From week 3, specific IgG antibody levels were higher in Fasciola
      infected than P. ohirai-infected rats. Sera from infected rats did not react with
      heterologous cysteine proteinases throughout the infection periods. In both
      infected groups, the kinetic patterns of specific IgM antibody responses were
      similar to those of specific IgG antibody responses although the ELISA levels of
      the IgM antibody responses were much lower. In abnormal infections with P. ohirai
      metacercariae x-irradiated at 2 krad, the specific IgG antibodies were detectable
      at week 2 postinfection with similar ELISA values to normal P. ohirai infection,
      but thereafter increased little. In infections with P. westermani, for which the
      rat is not a suitable host, even stunted worms induced a comparable specific IgG
      antibody response, although the response was lower than in normal infections with
      P. ohirai. These results indicate that cystatin capture ELISA can distinguish
      clearly between Paragonimus and Fasciola infections which show immunodiagnostic
      cross-reactivity and is useful even in the early stages of the infection and in
      the infection of unsuitable hosts.

PMID- 9765370
TI  - The structuring process of the macroparasite community of an experimental
      population of cichlasoma urophthalmus through time 
AB  - The structuring process of the macroparasite community of caged Cichlasoma
      urophthalmus was studied over time using sentinel fish. Three thousand uninfected
      cichlids were stocked in floating cages introduced into a quarry in which a wild
      population of the same species was present. Caged and wild cichlids were sampled
      monthly over 6 and 7 months, respectively. Seventeen macroparasite species were
      found in the wild C. urophthalmus population, ten of which were detected in the
      caged population after 6 months. Early infections were by those species that were
      more frequent and abundant in the wild population, while helminths with a low
      prevalence and abundance in the wild appeared later in the caged fish population.
      The results suggested that the structuring process of the macroparasite community
      of caged C. urophthalmus followed a predictable pattern, in which those species
      that were most frequent and abundant in the wild were the first to establish in
      sentinel fish.

PMID- 9765369
TI  - Characterization of Fasciola hepatica redial generations by morphometry and
      chaetotaxy under experimental conditions.
AB  - Morphometric and chaetotactic studies were carried out on the body and cephalic
      regions of the rediae of Fasciola hepatica (Trematoda: Fasciolidae) in order to
      precisely identify the different redial generations of this trematode in Lymnaea
      truncatula under experimental infection. At day 49 post-exposure at 20 degreesC,
      the length of the redia was significantly higher in the first group of the first
      generation (R1a) compared with successive generations, R1b, R2a and R2b/R3a. The
      width of the body was similar in the R1a, R1b, and R2a rediae, but was
      significantly lower in the R2b/R3a groups. The intrapharyngeal cavity of R1a
      rediae was significantly wider compared with the R1b, R2a, and R2b/R3a groups,
      whereas the pharyngeal wall was significantly thicker in the R2b/R3a rediae
      compared with the R1b and R2a groups. Four other measurements, namely the maximum
      length and width of the pharynx, diameter of the mouth, and width of intestine,
      also showed significant variations in relation to pharyngeal morphology and age
      of infection. Discriminant analysis based on these measurements demonstrated that
      98% of the rediae were readily categorized into the four groups identified. The
      number of perioral sensillae ranged from 126 to 160 but a significant difference
      was only noted between the mean values of the first generation and those of the
      group R2b/R3a. From these parameters, the maximum width of the pharyngeal lumen
      was found to be the best characteristic in the identification of the redial
      generations.

PMID- 9765371
TI  - Comparison of the trapping ability of Arthrobotrys robusta and Monacrosporium
      gephyropagum on infective larvae of Strongyloides papillosus.
AB  - In an in vitro trial, the trapping ability of Arthrobotrys robusta and
      Monacrosporium gephyropagum against Strongyloides papillosus infective larvae on
      corn meal agar plates, was evaluated after seven days of interaction at 25
      degrees C. Monacrosporium gephyropagum trapped 93.1% of the larvae whereas A.
      robusta trapped only 32.3%. Variability in the capture of S. papillosus infective
      larvae by both trapping fungi is discussed.

PMID- 9765372
TI  - Surface ultrastructure of juvenile and adult stages of Centrocestus armatus.
AB  - Centrocestus armatus (Trematoda: Heterophyidae) develops rapidly and produces
      eggs at 3 days postinfection in albino rats. Excysted metacercariae are pear
      shaped and concave ventrally, with 42-44 peg-like circumoral spines. The entire
      body surface is densely covered with scale-like serrated spines. On juveniles,
      serration of the tegumental spines is greatest in the middle of the ventral and
      dorsal surfaces, and decreases anteriorly and posteriorly. Ciliated sensory
      papillae are concentrated around the oral sucker. Several nonciliated sensory
      papillae (type II papillae) occur equidistantly on the acetabulum and are
      arranged in a linear symmetry on the dorsal surface. On adults, the serration of
      the tegumental spines decreases to 14-17 tips on the ventrolateral surface. The
      high density of tegumental spines on posterior half of the body and the
      distribution of type II papillae on dorsal surface are considered to be
      characteristic of C. armatus.

PMID- 9765373
TI  - Helminth fauna of the Iberian lynx, Lynx pardinus.
AB  - Specimens of 12 helminth species were collected from carcasses of eight Lynx
      pardinus (Temminck, 1827), a carnivore endemic to the Iberian Peninsula. These
      species included: Brachylaima sp. (12.5%) (Trematoda); Taenia pisiformis (12.5%),
      T. polyacantha (25%), T. taeniaeformis (25%) and Mesocestoides litteratus (37.5%)
      (Cestoda); Eucoleus aerophilus (12.5%), Ancylostoma tubaeforme (12.5%), Toxocara
      cati (37.5%), Toxascaris leonina (62.5%), Vigisospirura potekhina potekhina
      (12.5%), Mastophorus muris (12.5%) and Physaloptera praeputialis (12.5%)
      (Nematoda). The helminth fauna in Iberian lynx is compared with that of L.
      canadensis and L. rufus in America, and for L. lynx in Eurasia. The potential
      relationships between the parasitological data and some geographical, historical
      and dietary factors are discussed.

PMID- 9765375
TI  - Ecology of proteocephalus torulosus in the blue bream (Abramis ballerus) fromthe
      oder river on the borders of germany and poland 
AB  - During studies on the ecology of fish helminths, the tapeworm Proteocephalus
      torulosus (Batsch, 1786) was frequently found in the intestine of the blue bream
      (Abramis ballerus) from the Oder River (Germany/Poland). In total, 633 fish,
      ranging between two and 16 years old, were sampled at monthly intervals over a
      two year period during 1993-1995. Statistically significant differences in the
      seasonal occurrence of the parasite in its fish host were observed. In 1993, the
      prevalence remained at a high level, ranging between 61. 9 and 100%. During the
      summer of 1994, this value decreased to 5.5% and remained low for the rest of the
      year. The pattern of mean intensity of infection was similar to that of the
      prevalence. In 1993, the mean intensity varied between 8.4 and 31.8 worms per
      infected fish, with a continual loss of worms being observed in the summer of
      1994. Changes in the amount of suspended particulate matter in water have been
      identified as the main cause of these observed differences in the course of
      infection of blue bream.

PMID- 9765374
TI  - An erratic parasitism found in the lungs of sheep during experimental infection
      with Fasciola gigantica (Japanese strain).
AB  - An erratic parasitism was observed in the lungs of sheep experimentally infected
      with Fasciola gigantica at autopsy 14 weeks after inoculation. Macroscopically,
      several hyperaemia of 7.5-12.5 mm in diameter were found on the surface of the
      lungs. Juvenile flukes detected in the lungs were much smaller than those in the
      liver of the same sheep. A slight inflammatory reaction was observed in the lungs
      and it is likely that the flukes had migrated in the pleural cavity for some
      time. Occasionally, a mixed thrombus with many eosinophils was found in the blood
      vessels adjacent to the bronchia, although no cough was observed clinically. This
      suggests that diagnosis of juvenile fluke is difficult not only by
      parasitological but also serological methods.

PMID- 9765376
TI  - The use of video-imaging to assess the sub-lethal impact of plant secondary
      compounds on Schistosoma mansoni miracidia.
AB  - The study describes methods developed for using video-imaging technology to
      record and measure the velocity of Schistosoma mansoni miracidia. The efficacy of
      the classical bioassay procedure (a qualitative behavioural assay) was compared
      with that of the new quantitative protocol, for assessing the sub-lethal impact
      of a larvicidal dichloromethane extract of the seeds of Millettia thonningii on
      miracidia. The new technique confirmed the efficacy of the classical bioassay for
      rapid determination of the lethal and sub-lethal impact of larvicides but also
      provided quantitative information on sub-lethal impacts on miracidial velocity
      and shape.

PMID- 9765377
TI  - Ultrastructure of the digestive and protonephridial systems of the metacercaria
      of euclinostomum multicaecum 
AB  - The structure of the digestive tract of Euclinostomum multicaecum (Digenea:
      Euclinostomatidae) is unusual, comprising several main lateral caeca which extend
      posteriorly and further divide, giving rise to numerous smaller branches which
      are widely distributed throughout the fluke. These multicaeca presumably promote
      nutrient absorption during rapid and prolonged feeding directly following
      excystment. The caecal wall consists of a syncytial gastrodermal epithelium,
      bearing loop-like lamellae which extend into the lumen and enclose spherical
      inclusion bodies and presumably also, increase the absorptive surface area. There
      was no evidence of endo- or exocytosis, nor were lysosomes, phagosomes or
      residual bodies observed. The gut caeca are supported by a fibrous basal lamina
      and an underlying layer of muscle fibres, while parenchymal cells occupy much of
      the extracellular space. The protonephridial system resembles that observed in
      other digeneans consisting of flame cells and collecting ducts which join to form
      a bladder that opens externally through a single excretory pore. The syncytial
      epithelium of the collecting ducts is elevated by numerous lamellae while the
      basal lamina is highly infolded. The luminal contents of these ducts comprise bar
      shaped crystalline structures, lipid droplets and electron-dense inclusion
      bodies. The excretory system is supported by a network of muscle fibres and
      parenchymal cells.

PMID- 9765378
TI  - Plagiorchis muris: recovery, growth and development in albino rats.
AB  - Metacercariae of Plagiorchis muris, obtained from naturally infected dragonflies,
      Sympetrum eroticum, successfully established in 4-week-old albino rats up to 14
      days post-infection (p.i.) but by day 28 p.i. the recovery rate had significantly
      decreased. The genital primordia in excysted metacercariae were differentiated
      into those of metraterm, Mehlis' gland, ovary and cirrus pouch, with the
      primordial testes appearing on day 1 p.i. The vitellaria and eggs in the uterus
      were present in flukes on days 2 and 4 p.i., respectively. Mature flukes were
      established in the lower part of the small intestine on day 5 p.i., with the peak
      of egg production occurring on day 14 p.i. Growth of the flukes continued up to
      day 28 p.i.

PMID- 9765380
TI  - Intestinal helminth communities in the green lizard, lacerta viridis, from
      bulgaria 
AB  - A data set comprising individual host/parasite lists from 100 Lacerta viridis
      (Reptilia: Lacertidae) belonging to four isolated populations in Bulgaria was
      studied. A total of seven helminth species was recovered (Leptophallus
      nigrovenosus, Plagiorchis molini, Oswaldocruzia filiformis, Spauligodon
      extenuatus, Skrjabinelazia hoffmanni, Physaloptera clausa and Mesocestoides sp.).
      Lacerta viridis is a new host record for the first five of these species.
      Communities of intestinal helminths of L. viridis consist of a few species which
      resulted in a low species richness, abundance and diversity of infracommunities,
      which exhibit substantial homogeneity among the four samples. A similar pattern
      of dominance of two nematode species leading to a relatively high community
      similarity at both infra- and component community levels was observed. While
      intestinal helminth communities in lizards from 'marginal' habitats were
      dominated by the host generalist, O. filiformis, those in hosts from 'typical'
      habitats were dominated by the lizard specialist S. extenuatus. The results
      indicate that the characteristics of the host's habitat are important in
      determining the composition rather than structure of intestinal helminth
      communities in L. viridis.

PMID- 9765379
TI  - The ultrastructure of the cuticle and sheath of infective juveniles of
      entomopathogenic steinernematid nematodes.
AB  - The ultrastructure of the cuticle of infective juveniles (IJs) of Steinernema
      carpocapsae (newly emerged and 80-day-old) and newly emerged IJs of S. riobravis,
      S. feltiae and S. glaseri was examined using transmission electron microscopy.
      The thickness of four distinctive layers of the cuticle was measured: epicuticle,
      cortical and median layer, striated layer and fibrous mat. The thickness of the
      cuticle was correlated with the size of the IJ. In the case of newly emerged IJs,
      the smallest species, S. carpocapsae, had a cuticle thickness of c. 270 nm
      compared with c. 460 nm for S. glaseri, the largest of the four species. The
      overall thickness of the cuticle or the thickness of the cuticle layers was not
      correlated with the ability of the IJs of the four species to survive desiccation
      per se. The major difference between newly emerged IJs of the four species was
      that S. carpocapsae had a proportionately thicker striated layer compared with
      the other three species. The significance of this is not known but it may be an
      adaptation involving the nictation behaviour of this species. A substantial
      change was observed in the cuticle of aged (80-day-old) IJs of S. carpocapsae,
      whereby the thickness of the cortical and median layer increased by more than
      100% and the overall thickness of the cuticle increased by about 50%. Two
      possible explanations for this increase are: (i) new material was synthesized; or
      (ii) the fluid content of this layer increased due to an increase in the
      permeability of the outer layers of the cuticle. The ultrastructure of the
      sheaths of S. feltiae and S. glaseri was also examined and, apart from S. glaseri
      having a thicker sheath, the structure of the sheath in both species was similar,
      with the epicuticle and striated layer still visible.

PMID- 9765381
TI  - Eosinophil chemotactic factors from cysticercoids of Hymenolepis nana.
AB  - A comparative study of eosinophil chemotactic factors was carried out using
      cysticercoids and oncospheres of Hymenolepis nana. Cysticercoids showed twice the
      chemotactic activity for eosinophils than the oncospheres. Eosinophilia induced
      by oncospheres and cysticercoids observed in secondary and primary infections,
      respectively, were discussed from the view point of the immunobiology of this
      parasite.

PMID- 9765382
TI  - A third-generation lentivirus vector with a conditional packaging system.
AB  - Vectors derived from human immunodeficiency virus (HIV) are highly efficient
      vehicles for in vivo gene delivery. However, their biosafety is of major concern.
      Here we exploit the complexity of the HIV genome to provide lentivirus vectors
      with novel biosafety features. In addition to the structural genes, HIV contains
      two regulatory genes, tat and rev, that are essential for HIV replication, and
      four accessory genes that encode critical virulence factors. We previously
      reported that the HIV type 1 accessory open reading frames are dispensable for
      efficient gene transduction by a lentivirus vector. We now demonstrate that the
      requirement for the tat gene can be offset by placing constitutive promoters
      upstream of the vector transcript. Vectors generated from constructs containing
      such a chimeric long terminal repeat (LTR) transduced neurons in vivo at very
      high efficiency, whether or not they were produced in the presence of Tat. When
      the rev gene was also deleted from the packaging construct, expression of gag and
      pol was strictly dependent on Rev complementation in trans. By the combined use
      of a separate nonoverlapping Rev expression plasmid and a 5' LTR chimeric
      transfer construct, we achieved optimal yields of vector of high transducing
      efficiency (up to 10(7) transducing units [TU]/ml and 10(4) TU/ng of p24). This
      third-generation lentivirus vector uses only a fractional set of HIV genes: gag,
      pol, and rev. Moreover, the HIV-derived constructs, and any recombinant between
      them, are contingent on upstream elements and trans complementation for
      expression and thus are nonfunctional outside of the vector producer cells. This
      split-genome, conditional packaging system is based on existing viral sequences
      and acts as a built-in device against the generation of productive recombinants.
      While the actual biosafety of the vector will ultimately be proven in vivo, the
      improved design presented here should facilitate testing of lentivirus vectors.

PMID- 9765383
TI  - Canine distemper virus DNA vaccination induces humoral and cellular immunity and
      protects against a lethal intracerebral challenge.
AB  - We have studied the immune responses to the two glycoproteins of the
      Morbillivirus canine distemper virus (CDV) after DNA vaccination of BALB/c mice.
      The plasmids coding for both CDV hemagglutinin (H) and fusion protein (F) induce
      high levels of antibodies which persist for more than 6 months. Intramuscular
      inoculation of the CDV DNA induces a predominantly immunoglobulin G2a (IgG2a)
      response (Th1 response), whereas gene gun immunization with CDV H evokes
      exclusively an IgG1 response (Th2 response). In contrast, the CDV F gene elicited
      a mixed, IgG1 and IgG2a response. Mice vaccinated (by gene gun) with either the
      CDV H or F DNA showed a class I-restricted cytotoxic lymphocyte response.
      Immunized mice challenged intracerebrally with a lethal dose of a neurovirulent
      strain of CDV were protected. However, approximately 30% of the mice vaccinated
      with the CDV F DNA became obese in the first 2 months following the challenge.
      This was not correlated with the serum antibody levels.

PMID- 9765384
TI  - High-mobility group 1/2 proteins are essential for initiating rolling-circle-type
      DNA replication at a parvovirus hairpin origin.
AB  - Rolling-circle replication is initiated by a replicon-encoded endonuclease which
      introduces a single-strand nick into specific origin sequences, becoming
      covalently attached to the 5' end of the DNA at the nick and providing a 3'
      hydroxyl to prime unidirectional, leading-strand synthesis. Parvoviruses, such as
      minute virus of mice (MVM), have adapted this mechanism to amplify their linear
      single-stranded genomes by using hairpin telomeres which sequentially unfold and
      refold to shuttle the replication fork back and forth along the genome, creating
      a continuous, multimeric DNA strand. The viral initiator protein, NS1, then
      excises individual genomes from this continuum by nicking and reinitiating
      synthesis at specific origins present within the hairpin sequences. Using in
      vitro assays to study ATP-dependent initiation within the right-hand (5') MVM
      hairpin, we have characterized a HeLa cell factor which is absolutely required to
      allow NS1 to nick this origin. Unlike parvovirus initiation factor (PIF), the
      cellular complex which activates NS1 endonuclease activity at the left-hand (3')
      viral origin, the host factor which activates the right-hand hairpin elutes from
      phosphocellulose in high salt, has a molecular mass of around 25 kDa, and appears
      to bind preferentially to structured DNA, suggesting that it might be a member of
      the high-mobility group 1/2 (HMG1/2) protein family. This prediction was
      confirmed by showing that purified calf thymus HMG1 and recombinant human HMG1 or
      murine HMG2 could each substitute for the HeLa factor, activating the NS1
      endonuclease in an origin-specific nicking reaction.

PMID- 9765385
TI  - The Epstein-Barr virus (EBV) SM protein enhances pre-mRNA processing of the EBV
      DNA polymerase transcript.
AB  - The Epstein-Barr virus (EBV) DNA polymerase (pol) mRNA, which contains a
      noncanonical polyadenylation signal, UAUAAA, is cleaved and polyadenylated
      inefficiently (S. C. S. Key and J. S. Pagano, Virology 234:147-159, 1997). We
      postulated that the EBV early proteins SM and M, which appear to act
      posttranscriptionally and are homologs of herpes simplex virus (HSV) ICP27, might
      compensate for the inefficient processing of pol pre-mRNA. Here we show that the
      SM and M proteins interact with each other in vitro. In addition, glutathione S
      transferase-SM/M fusion proteins precipitate the heterogeneous ribonucleoprotein
      (hnRNP) C1 splicing protein. Further, the SM protein is coimmunoprecipitated from
      SM-expressing cell extracts with an antibody to the hnRNP A1/A2 proteins, which
      are splicing and nuclear shuttling proteins. Finally, the amount of processed EBV
      DNA polymerase mRNA was increased three- to fourfold in a HeLa cell line
      expressing SM; this increase was not due to enhanced transcription. Thus,
      inefficient processing of EBV pol RNA by cellular cleavage and polyadenylation
      factors appears to be compensated for and may be regulated by the early EBV
      protein, SM, perhaps via RNA 3'-end formation.

PMID- 9765386
TI  - Molecular evidence for mother-to-child transmission of multiple variants by
      analysis of RNA and DNA sequences of human immunodeficiency virus type 1.
AB  - We have examined the viral selection that may occur during transmission by
      studying the env gene sequences from four cases of mother-to-child transmission
      of human immunodeficiency virus type 1. The V3 region sequences were directly
      amplified from both plasma viral RNA and peripheral blood mononuclear cells
      containing proviral DNA from mothers at delivery and at the time of diagnosis for
      children. Transmission occurred perinatally in three cases. The similarity of the
      viral sequences in each infant sample contrasted with the heterogeneous viral
      populations in the mothers. Phylogenetic analysis indicated the transmission of
      one or a few closely related maternal minor virus variants. In contrast, the
      child virus population in the fourth case was as heterogeneous as that of his
      mother, and phylogenetic analysis strongly suggested the transmission of multiple
      maternal variants. This case of multiple transmission was confirmed by analyzing
      sequences obtained at three times after delivery. Strains with sequences
      corresponding to the syncytium-inducing phenotype were also transmitted in this
      fourth case, and this was associated with the rapid development of disease in the
      child. There was no evidence for transmission of particular viral variants from
      mother to infant. We have thus described a particular case of vertical human
      immunodeficiency virus type 1 transmission with the transmission of multiple
      maternal variants to the infant and a rapid, fatal outcome in the child.

PMID- 9765387
TI  - Enhancer requirement for murine cytomegalovirus growth and genetic
      complementation by the human cytomegalovirus enhancer.
AB  - The cytomegalovirus (CMV) enhancer is a highly complex regulatory region
      containing multiple elements that interact with a variety of host-encoded
      transcription factors. Many of these sequence elements are conserved among the
      different species strains of CMV, although the arrangement of the various
      elements and overall sequence composition of the CMV enhancers differ remarkably.
      To delineate the importance of this region to a productive infection and to
      explore the possibility of generating a murine CMV (MCMV) under the control of
      human CMV (HCMV) genetic elements, the MCMV enhancer was resected and replaced
      either with nonregulatory sequences or with paralogous sequences from HCMV. The
      effects of these various deletions and substitutions on viral growth in
      transfected or infected tissue-culture cells were evaluated. We found that
      mutations in MCMV that eliminate or substitute for the enhancer with
      nonregulatory sequences showed a severe deficiency in virus synthesis. This
      growth defect is effectively complemented by the homologous MCMV enhancer as well
      as the HCMV enhancer. In the latter case, the chimeric viruses (hybrid MCMV
      strains) containing the molecularly shuffled human enhancer exhibit infectious
      kinetics similar to that of parental wild-type and wild-type revertant MCMV.
      These results also show that open reading frames m124, m124.1, and m125 located
      within the enhancer region are nonessential for growth of MCMV in cells. Most
      importantly, we conclude that the enhancer of MCMV is required for optimal
      infection and that its diverged human counterpart can advantageously replace its
      role in promoting viral infectivity.

PMID- 9765389
TI  - Coronavirus transcription early in infection.
AB  - We studied the accumulation kinetics of murine coronavirus mouse hepatitis virus
      (MHV) RNAs early in infection by using cloned MHV defective interfering (DI) RNA
      that contained an intergenic sequence from which subgenomic DI RNA is synthesized
      in MHV-infected cells. Genomic DI RNA and subgenomic DI RNA accumulated at a
      constant ratio from 3 to 11 h postinfection (p.i.) in the cells infected with MHV
      containing DI particles. Earlier, at 1 h p.i., this ratio was not constant; only
      genomic DI RNA accumulated, indicating that MHV RNA replication, but not MHV RNA
      transcription, was active during the first hour of MHV infection. Negative-strand
      genomic DI RNA and negative-strand subgenomic DI RNA were first detectable at 1
      and 3 h p.i., respectively, and the amounts of both RNAs increased gradually
      until 6 h p.i. These data showed that at 2 h p.i., subgenomic DI RNA was
      undergoing synthesis in the cells in which negative-strand subgenomic DI RNA was
      undetectable. These data, therefore, signify that negative-strand genomic DI RNA,
      but not negative-strand subgenomic DI RNA, was an active template for subgenomic
      DI RNA synthesis early in infection.

PMID- 9765388
TI  - Inactivation of p53 but not p73 by adenovirus type 5 E1B 55-kilodalton and E4 34
      kilodalton oncoproteins.
AB  - The adenovirus E1B 55-kDa and E4 34-kDa oncoproteins bind and inactivate the p53
      tumor suppressor gene product, resulting in cell transformation. A recently
      discovered cellular protein, p73, shows extensive similarities to p53 in
      structure and function. Here we show that the simultaneous transient expression
      of E1B 55-kDa and E4 34-kDa proteins is sufficient to drastically shorten the
      intracellular half-life of p53, leading to strongly reduced steady-state p53
      levels. Concomitantly, the E1B 55-kDa and E4 34-kDa proteins act synergistically
      to inactivate the transcriptional activity of p53. Mutational analysis suggests
      that physical interactions between the E1B 55-kDa protein and p53 and between the
      E1B 55-kDa and E4 34-kDa proteins are both required for p53 degradation. In
      contrast, the ability of p53 to interact with the cellular mdm2 oncoprotein or
      with its cognate DNA element appears to be dispensable for its destabilization by
      adenovirus gene products. The adenovirus E1B 55-kDa protein did not detectably
      interact with p73 and failed to inhibit p73-mediated transcription; also, the E1B
      55-kDa and E4 34-kDa proteins did not promote p73 degradation. When five amino
      acids near the amino termini were exchanged at corresponding positions between
      p53 and p73, this rendered p53 resistant and p73 susceptible to complex formation
      and inactivation by the E1B 55-kDa protein. Our results suggest that while p53
      inactivation is a central step in virus-induced tumor development, efficient
      transformation can occur without targeting p73.

PMID- 9765390
TI  - Herpes simplex virus 1 regulatory protein ICP22 interacts with a new cell cycle
      regulated factor and accumulates in a cell cycle-dependent fashion in infected
      cells.
AB  - The herpes simplex virus 1 infected cell protein 22 (ICP22), the product of the
      alpha22 gene, is a nucleotidylylated and phosphorylated nuclear protein with
      properties of a transcriptional factor required for the expression of a subset of
      viral genes. Here, we report the following. (i) ICP22 interacts with a previously
      unknown cellular factor designated p78 in the yeast two-hybrid system. The p78
      cDNA encodes a polypeptide with a distribution of leucines reminiscent of a
      leucine zipper. (ii) In uninfected and infected cells, antibody to p78 reacts
      with two major bands with an apparent Mr of 78,000 and two minor bands with
      apparent Mrs of 62, 000 and 55,000. (ii) p78 also interacts with ICP22 in vitro.
      (iii) In uninfected cells, p78 was dispersed largely in the nucleoplasm in HeLa
      cells and in the nucleoplasm and cytoplasm in HEp-2 cells. After infection, p78
      formed large dense bodies which did not colocalize with the viral regulatory
      protein ICP0. (iv) Accumulation of p78 was cell cycle dependent, being highest
      very early in S phase. (v) The accumulation of ICP22 in synchronized cells was
      highest in early S phase, in contrast to the accumulation of another protein,
      ICP27, which was relatively independent of the cell cycle. (vi) In the course of
      the cell cycle, ICP22 was transiently modified in an aberrant fashion, and this
      modification coincided with expression of p78. The results suggest that ICP22
      interacts with and may be stabilized by cell cycle-dependent proteins.

PMID- 9765391
TI  - Specific interaction of heterogeneous nuclear ribonucleoprotein particle U with
      the leader RNA sequence of vesicular stomatitis virus.
AB  - The 3' ends of the genome and antigenome RNA of vesicular stomatitis virus (VSV)
      serve as the promoter sites for the RNA-dependent RNA polymerase in the
      initiation of transcription and replication, respectively. The leader RNA, the
      first transcript synthesized during the RNA synthetic step, contains sequences to
      initiate encapsidation with the nucleocapsid protein, which is a prerequisite for
      replication. It also plays a role in the inhibition of cellular RNA synthesis. To
      search for a specific cellular factor(s) which may interact with the leader RNA
      sequences and regulate these processes, we used a gel mobility shift assay to
      identify such a protein(s). By using nuclear extract, it was found that in
      addition to the previously reported La protein, a 120-kDa nuclear protein
      specifically interacts with the leader RNA. Biochemical and immunological studies
      identified the 120-kDa protein as heterogeneous nuclear ribonucleoprotein
      particle U (hnRNP U), which is involved in pre-mRNA processing. We also
      demonstrate that hnRNP U is associated with the leader RNA in the nuclei of VSV
      infected cells and also packaged within the purified virions. By double
      immunofluorescence labeling and confocal microscopy, hnRNP U appears to
      colocalize with the virus in the cytoplasm of infected cells. These results
      strongly suggest that hnRNP U plays an important role in the life cycle of VSV.

PMID- 9765392
TI  - Structure of double-shelled rice dwarf virus.
AB  - Rice dwarf virus (RDV), a member of the Reoviridae family, is a double-stranded
      RNA virus. Infection of rice plants with RDV reduces crop production
      significantly and can pose a major economic threat to Southeast Asia. A 25-A
      three-dimensional structure of the 700-A-diameter RDV capsid has been determined
      by 400-kV electron cryomicroscopy and computer reconstruction. The structure
      revealed two distinctive icosahedral shells: a T=13l outer icosahedral shell
      composed of 260 trimeric clusters of P8 (46 kDa) and an inner T=1 icosahedral
      shell of 60 dimers of P3 (114 kDa). Sequence and structural comparisons were made
      between the RDV outer shell trimer and the two crystal conformations (REF and
      HEX) of the VP7 trimer of bluetongue virus, an animal analog of RDV. The low
      resolution structural match of the RDV outer shell trimer to the HEX conformation
      of VP7 trimer has led to the proposal that P8 consists of an upper domain of beta
      sandwich motif and a lower domain of alpha helices. The less well fit REF
      conformation of VP7 to the RDV trimer may be due to the differences between VP7
      and P8 in the sequence of the hinge region that connects the two domains. The
      additional mass density and the absence of a known signaling peptide on the
      surface of the RDV outer shell trimer may be responsible for the different
      interactions between plants and animal reoviruses.

PMID- 9765393
TI  - The role of interferon in influenza virus tissue tropism.
AB  - We have studied the pathogenesis of influenza virus infection in mice that are
      unable to respond to type I or II interferons due to a targeted disruption of the
      STAT1 gene. STAT1-/- animals are 100-fold more sensitive to lethal infection with
      influenza A/WSN/33 virus than are their wild-type (WT) counterparts. Virus
      replicated only in the lungs of WT animals following intranasal (i.n.) virus
      inoculation, while STAT1-/- mice developed a fulminant systemic influenza virus
      infection following either i.n. or intraperitoneal inoculation. We investigated
      the mechanism underlying this altered virus tropism by comparing levels of virus
      replication in fibroblast cell lines and murine embryonic fibroblasts derived
      from WT mice, STAT-/- mice, and mice lacking gamma interferon (IFNgamma-/- mice)
      or the IFN-alpha receptor (IFNalphaR-/- mice). Influenza A/WSN/33 virus
      replicates to high titers in STAT1-/- or IFNalphaR-/- fibroblasts, while cells
      derived from WT or IFNgamma-/- animals are resistant to influenza virus
      infection. Immunofluorescence studies using WT fibroblast cell lines demonstrated
      that only a small subpopulation of WT cells can be infected and that in the few
      infected WT cells, virus replication is aborted at an early, nuclear phase. In
      all organs examined except the lung, influenza A WSN/33 virus infection is
      apparently prevented by an intact type I interferon response. Our results
      demonstrate that type I interferon plays an important role in determining the
      pathogenicity and tissue restriction of influenza A/WSN/33 virus in vivo and in
      vitro.

PMID- 9765395
TI  - Circular intermediates of recombinant adeno-associated virus have defined
      structural characteristics responsible for long-term episomal persistence in
      muscle tissue.
AB  - Adeno-associated viral (AAV) vectors have demonstrated great utility for long
      term gene expression in muscle tissue. However, the mechanisms by which
      recombinant AAV (rAAV) genomes persist in muscle tissue remain unclear. Using a
      recombinant shuttle vector, we have demonstrated that circularized rAAV
      intermediates impart episomal persistence to rAAV genomes in muscle tissue. The
      majority of circular intermediates had a consistent head-to-tail configuration
      consisting of monomer genomes which slowly converted to large multimers of >12
      kbp by 80 days postinfection. Importantly, long-term transgene expression was
      associated with prolonged (80-day) episomal persistence of these circular
      intermediates. Structural features of these circular intermediates responsible
      for increased persistence included a DNA element encompassing two viral inverted
      terminal repeats (ITRs) in a head-to-tail orientation, which confers a 10-fold
      increase in the stability of DNA following incorporation into plasmid-based
      vectors and transfection into HeLa cells. These studies suggest that certain
      structural characteristics of AAV circular intermediates may explain long-term
      episomal persistence with this vector. Such information may also aid in the
      development of nonviral gene delivery systems with increased efficiency.

PMID- 9765394
TI  - The Epstein-Barr virus lytic transactivator Zta interacts with the helicase
      primase replication proteins.
AB  - The Epstein-Barr virus transactivator Zta triggers lytic gene expression and is
      essential for replication of the lytic origin, oriLyt. Previous analysis
      indicated that the Zta activation domain contributed a replication-specific
      function. We now show that the Zta activation domain interacts with components of
      the EBV helicase-primase complex. The three helicase-primase proteins BBLF4
      (helicase), BSLF1 (primase), and BBLF2/3 (primase-associated factor) were
      expressed fused to the Myc epitope. When expression plasmids for BBLF4 or BBLF2/3
      plus BSLF1 (primase subcomplex) were separately transfected, the proteins
      localized to the cytoplasm. Interaction between Zta and the components of the
      helicase-primase complex was tested by examining the ability of Zta to alter the
      intracellular localization of these proteins. Cotransfection of Zta with Myc
      BBLF4 resulted in nuclear translocation of Myc-BBLF4; similarly, cotransfection
      of Zta with the primase subcomplex led to nuclear translocation of the Myc-BSLF1
      and Myc-BBLF2/3 proteins. This relocalization provides evidence for an
      interaction between Zta and the helicase and Zta and the primase subcomplex. An
      affinity assay using glutathione S-transferase-Zta fusion proteins demonstrated
      that Myc-BBLF4 and Myc-BBLF2/3 plus BSLF1 bound to the Zta activation domain
      (amino acids 1 to 133). In the nuclear relocalization assay, the amino-terminal
      25 amino acids of Zta were required for efficient interaction with the primase
      subcomplex but not for interaction with BBLF4. Evidence for interaction between
      oriLyt bound Zta and the helicase-primase complex was obtained in a
      superactivation assay using an oriLyt-chloramphenicol acetyltransferase (CAT)
      reporter. Zta activated expression from a CAT reporter containing the complete
      oriLyt region and regulated by the oriLyt BHLF1 promoter. Cotransfection of the
      helicase-primase proteins, one of which was fused to a heterologous activation
      domain, led to Zta-dependent superactivation of CAT expression. This assay also
      provided evidence for an interaction between the single-stranded DNA binding
      protein, BALF2, and the Zta-tethered helicase-primase complex. The helicase
      primase interaction is consistent with a role for Zta in stabilizing the
      formation of an origin-bound replication complex.

PMID- 9765396
TI  - Intracellular localization of poliovirus plus- and minus-strand RNA visualized by
      strand-specific fluorescent In situ hybridization.
AB  - The time courses of poliovirus plus- and minus-strand RNA synthesis in infected
      HEp-2 cells were monitored separately, using a quantitative RNase assay. In
      parallel, viral RNA and proteins were located in situ by confocal microscopy
      within cells fixed by a protocol determined to retain their native size and
      shape. Plus- and minus-strand RNAs were visualized by fluorescent in situ
      hybridization (FISH) with strand-specific riboprobes. The probes were labelled
      with different fluorochromes to allow for the simultaneous detection of plus- and
      minus-strand RNA. The FISH experiments showed minus-strand RNA to be present in
      distinct, regularly sized, round structures throughout the viral replication
      cycle. Plus-strand RNA was found in the same structures and also in smaller
      clusters of vesicles. Association of viral RNA with membranes was demonstrated by
      combining FISH with immunofluorescence (IF) detection of the viral 2B- and 2C
      containing P2 proteins, which are known to be markers for virus-induced
      membranes. At early times postinfection, the virus-induced membranous structures
      were distributed through most of the cytoplasm, whereas around peak RNA
      synthesis, both RNA-associated membranous structures migrated to the center of
      the cell. During this process, the plus- and minus-strand-containing larger
      structures stayed as recognizable entities, whereas the plus-strand-containing
      granules coalesced into a juxtanuclear area of membranous vesicles. An
      involvement of Golgi-derived membranes in the formation of virus-induced vesicles
      and RNA synthesis early in infection was investigated by IF with 2C- and Golgi
      specific antibodies.

PMID- 9765398
TI  - Reovirus growth in cell culture does not require the full complement of viral
      proteins: identification of a sigma1s-null mutant.
AB  - The reovirus sigma1s protein is a 14-kDa nonstructural protein encoded by the S1
      gene segment. The S1 gene has been linked to many properties of reovirus,
      including virulence and induction of apoptosis. Although the function of sigma1s
      is not known, the sigma1s open reading frame is conserved in all S1 gene
      sequences determined to date. In this study, we identified and characterized a
      variant of type 3 reovirus, T3C84-MA, which does not express sigma1s. To
      facilitate these experiments, we generated two monoclonal antibodies (MAbs) that
      bind different epitopes of the sigma1s protein. Using these MAbs in immunoblot
      and immunofluorescence assays, we found that L929 (L) cells infected with T3C84
      MA do not contain sigma1s. To determine whether sigma1s is required for reovirus
      infection of cultured cells, we compared the growth of T3C84-MA and its parental
      strain, T3C84, in L cells and Madin-Darby canine kidney (MDCK) cells. After 48 h
      of growth, yields of T3C84-MA were equivalent to yields of T3C84 in L cells and
      were fivefold lower than yields of T3C84 in MDCK cells. After 7 days of growth
      following adsorption at a low multiplicity of infection, yields of T3C84-MA and
      T3C84 did not differ significantly in either L cells or MDCK cells. To determine
      whether sigma1s is required for apoptosis induced by reovirus infection, T3C84-MA
      and T3C84 were tested for their capacity to induce apoptosis, using an acridine
      orange staining assay. In these experiments, the percentages of apoptotic cells
      following infection with T3C84-MA and T3C84 were equivalent. These findings
      indicate that nonstructural protein sigma1s is not required for reovirus growth
      in cell culture and does not influence the capacity of reovirus to induce
      apoptosis. Therefore, reovirus replication does not require the full complement
      of virally encoded proteins.

PMID- 9765397
TI  - Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2
      interacting protein.
AB  - bcl-2, the prototypic cellular antiapoptotic gene, decreases Sindbis virus
      replication and Sindbis virus-induced apoptosis in mouse brains, resulting in
      protection against lethal encephalitis. To investigate potential mechanisms by
      which Bcl-2 protects against central nervous system Sindbis virus infection, we
      performed a yeast two-hybrid screen to identify Bcl-2-interacting gene products
      in an adult mouse brain library. We identified a novel 60-kDa coiled-coil
      protein, Beclin, which we confirmed interacts with Bcl-2 in mammalian cells,
      using fluorescence resonance energy transfer microscopy. To examine the role of
      Beclin in Sindbis virus pathogenesis, we constructed recombinant Sindbis virus
      chimeras that express full-length human Beclin (SIN/beclin), Beclin lacking the
      putative Bcl-2-binding domain (SIN/beclinDeltaBcl-2BD), or Beclin containing a
      premature stop codon near the 5' terminus (SIN/beclinstop). The survival of mice
      infected with SIN/beclin was significantly higher (71%) than the survival of mice
      infected with SIN/beclinDeltaBcl-2BD (9%) or SIN/beclinstop (7%) (P < 0.001). The
      brains of mice infected with SIN/beclin had fewer Sindbis virus RNA-positive
      cells, fewer apoptotic cells, and lower viral titers than the brains of mice
      infected with SIN/beclinDeltaBcl-2BD or SIN/beclinstop. These findings
      demonstrate that Beclin is a novel Bcl-2-interacting cellular protein that may
      play a role in antiviral host defense.

PMID- 9765399
TI  - A protein critical for a Theiler's virus-induced immune system-mediated
      demyelinating disease has a cell type-specific antiapoptotic effect and a key
      role in virus persistence.
AB  - TO subgroup strains of Theiler's murine encephalomyelitis virus (TMEV) induce a
      persistent central nervous system infection and demyelinating disease in mice.
      This disease serves as an experimental model of multiple sclerosis (MS) because
      the two diseases have similar inflammatory white matter pathologies and because
      the immune system appears to mediate demyelination in both processes. We
      previously reported (H. H. Chen, W. P. Wong, L. Zhang, P. L. Ward, and R. P.
      Roos, Nat. Med. 1:927-931, 1995) that TO subgroup strains use an alternative
      initiation codon (in addition to the AUG used to synthesize the picornavirus
      polyprotein from one long open reading frame) to translate L*, a novel protein
      that is out of frame with the polyprotein and which plays a key role in the
      demyelinating disease. We now demonstrate that L* has antiapoptotic activity in
      macrophage cells and is critical for virus persistence. The antiapoptotic action
      of L* as well as the differential translation of L* and virion capsid proteins
      may foster virus persistence in macrophages and interfere with virus clearance.
      The regulation of apoptotic activity in inflammatory cells may be important in
      the pathogenesis of TMEV-induced demyelinating disease as well as MS.

PMID- 9765400
TI  - Dissemination of lymphocytic choriomeningitis virus from the gastric mucosa
      requires G protein-coupled signaling.
AB  - The gastric mucosa is an important portal of entry for lymphocytic
      choriomeningitis virus (LCMV) infections. Within hours after intragastric (i.g.)
      inoculation, virus appears in the gastric epithelia, then in the mesenteric lymph
      nodes and spleen, and then in the liver and brain. By 72 h i.g.-inoculated virus
      is widely disseminated and equivalent to intravenous (i.v.) infection (S. K. Rai,
      B. K. Micales, M. S. Wu, D. S. Cheung, T. D. Pugh, G. E. Lyons, and M. S.
      Salvato. Am. J. Pathol. 151:633-639, 1997). Pretreatment of mice with a G protein
      inhibitor, pertussis toxin (PTx), delays LCMV dissemination after i.g., but not
      after i.v., inoculation. Delayed infection was confirmed by plaque assays, by
      reverse transcription-PCR, and by in situ hybridization. The differential PTx
      effect on i.v. and i.g. infections indicates that dissemination from the gastric
      mucosa requires signals transduced through heterotrimeric G protein complexes.
      PTx has no direct effect on LCMV replication, but it modulates integrin
      expression in part by blocking chemokine signals. LCMV infection of macrophages
      up-regulates CD11a, and PTx treatment counteracts this. PTx may prevent early
      LCMV dissemination by inhibiting the G protein-coupled chemotactic response of
      macrophages infected during the initial exposure, thus blocking systemic virus
      spread.

PMID- 9765401
TI  - The herpes simplex virus US11 protein effectively compensates for the
      gamma1(34.5) gene if present before activation of protein kinase R by precluding
      its phosphorylation and that of the alpha subunit of eukaryotic translation
      initiation factor 2.
AB  - In herpes simplex virus-infected cells, viral gamma134.5 protein blocks the
      shutoff of protein synthesis by activated protein kinase R (PKR) by directing the
      protein phosphatase 1alpha to dephosphorylate the alpha subunit of eukaryotic
      translation initiation factor 2 (eIF-2alpha). The amino acid sequence of the
      gamma134.5 protein which interacts with the phosphatase has high homology to a
      domain of the eukaryotic protein GADD34. A class of compensatory mutants
      characterized by a deletion which results in the juxtaposition of the alpha47
      promoter next to US11, a gamma2 (late) gene in wild-type virus-infected cells,
      has been described. In cells infected with these mutants, protein synthesis
      continues even in the absence of the gamma134.5 gene. In these cells, PKR is
      activated but eIF-2alpha is not phosphorylated, and the phosphatase is not
      redirected to dephosphorylate eIF-2alpha. We report the following: (i) in cells
      infected with these mutants, US11 protein was made early in infection; (ii) US11
      protein bound PKR and was phosphorylated; (iii) in in vitro assays, US11 blocked
      the phosphorylation of eIF-2alpha by PKR activated by poly(I-C); and (iv) US11
      was more effective if present in the reaction mixture during the activation of
      PKR than if added after PKR had been activated by poly(I-C). We conclude the
      following: (i) in cells infected with the compensatory mutants, US11 made early
      in infection binds to PKR and precludes the phosphorylation of eIF-2alpha,
      whereas US11 driven by its natural promoter and expressed late in infection is
      ineffective; and (ii) activation of PKR by double-stranded RNA is a common
      impediment countered by most viruses by different mechanisms. The gamma134.5 gene
      is not highly conserved among herpesviruses. A likely scenario is that
      acquisition by a progenitor of herpes simplex virus of a portion of the cellular
      GADD34 gene resulted in a more potent and reliable means of curbing the effects
      of activated PKR. US11 was retained as a gamma2 gene because, like many viral
      proteins, it has multiple functions.

PMID- 9765404
TI  - Immediate-early transactivator Rta of Epstein-Barr virus (EBV) shows multiple
      epitopes recognized by EBV-specific cytotoxic T lymphocytes.
AB  - We analyzed the immediate-early transactivator Rta of Epstein-Barr virus (EBV)
      for its role as a target for specific cytotoxic T lymphocytes (CTL). Panels of
      overlapping peptides covering the entire amino acid sequence of Rta were
      synthesized and used to induce and analyze specific CTL responses in EBV-positive
      donors. Using peptide-pulsed target cells, we found nine different CTL epitopes
      that are distributed over the entire protein sequence. One epitope restricted by
      HLA-A24 could be mapped to the decameric sequence DYCNVLNKEF between amino acid
      positions 28 and 37 of the Rta protein. A second epitope could be assigned to the
      same region of Rta (residues 25 to 39) and was shown to be restricted by HLA-B18.
      Another, minimal epitope could be mapped to the nonameric sequence ATIGTAMYK
      between amino acid positions 134 and 142; this peptide was restricted by HLA-A11.
      Another four epitopes were proven to be restricted by HLA-A2, -A3, -B61, and -Cw4
      and were located between Rta residues 225 and 239, 145 and 159, 529 and 543, and
      393 and 407, respectively. For two other epitopes, only the location within the
      Rta protein is known so far (residues 121 to 135 and 441 to 455); their exact HLA
      restriction patterns have not yet been identified. Using target cells infected
      with recombinant vaccinia virus containing the gene for Rta, we showed that six
      of eight Rta-specific CTL lines recognized the corresponding peptides also after
      endogenous processing. These data suggest that Rta comprises an important target
      for EBV-specific cellular cytotoxicity. Together with recent findings of other
      immediate-early and early proteins also acting as CTL targets, they reveal the
      role of proteins of the lytic cycle in the immune recognition of EBV-infected
      cells.

PMID- 9765403
TI  - Coronavirus pseudoparticles formed with recombinant M and E proteins induce alpha
      interferon synthesis by leukocytes.
AB  - Transmissible gastroenteritis virus (TGEV), an enteric coronavirus of swine, is a
      potent inducer of alpha interferon (IFN-alpha) both in vivo and in vitro.
      Incubation of peripheral blood mononuclear cells with noninfectious viral
      material such as inactivated virions or fixed, infected cells leads to early and
      strong IFN-alpha synthesis. Previous studies have shown that antibodies against
      the virus membrane glycoprotein M blocked the IFN induction and that two viruses
      with a mutated protein exhibited a decreased interferogenic activity, thus
      arguing for a direct involvement of M protein in this phenomenon. In this study,
      the IFN-alpha-inducing activity of recombinant M protein expressed in the absence
      or presence of other TGEV structural proteins was examined. Fixed cells
      coexpressing M together with at least the minor structural protein E were found
      to induce IFN-alpha almost as efficiently as TGEV-infected cells. Pseudoparticles
      resembling authentic virions were released in the culture medium of cells
      coexpressing M and E proteins. The interferogenic activity of purified
      pseudoparticles was shown to be comparable to that of TGEV virions, thus
      establishing that neither ribonucleoprotein nor spikes are required for IFN
      induction. The replacement of the externally exposed, N-terminal domain of M with
      that of bovine coronavirus (BCV) led to the production of chimeric particles with
      no major change in interferogenicity, although the structures of the TGEV and BCV
      ectodomains markedly differ. Moreover, BCV pseudoparticles also exhibited
      interferogenic activity. Together these observations suggest that the ability of
      coronavirus particles to induce IFN-alpha is more likely to involve a specific,
      multimeric structure than a definite sequence motif.

PMID- 9765402
TI  - Inhibition of human immunodeficiency virus Rev and human T-cell leukemia virus
      Rex function, but not Mason-Pfizer monkey virus constitutive transport element
      activity, by a mutant human nucleoporin targeted to Crm1.
AB  - The hypothesis that the cellular protein Crm1 mediates human immunodeficiency
      virus type 1 (HIV-1) Rev-dependent nuclear export posits that Crm1 can directly
      interact both with the Rev nuclear export signal (NES) and with cellular
      nucleoporins. Here, we demonstrate that Crm1 is indeed able to interact with
      active but not defective forms of the HIV-1 Rev NES and of NESs found in other
      retroviral nuclear export factors. In addition, we demonstrate that Crm1 can bind
      the Rev NES when Rev is assembled onto the Rev response element RNA target and
      that Crm1, like Rev, is a nucleocytoplasmic shuttle protein. Crm1 also
      specifically binds the Rev NES in vitro, although this latter interaction is
      detectable only in the presence of added Ran . GTP. Overexpression of a
      truncated, defective form of the nucleoporin Nup214/CAN, termed DeltaCAN, that
      retains Crm1 binding ability resulted in the effective inhibition of HIV-1 Rev or
      human T-cell leukemia virus Rex-dependent gene expression. In contrast, DeltaCAN
      had no significant affect on Mason-Pfizer monkey virus constitutive transport
      element (MPMV CTE)-dependent nuclear RNA export or on the expression of RNAs
      dependent on the cellular mRNA export pathway. As a result, DeltaCAN specifically
      blocked late, but not early, HIV-1 gene expression in HIV-1-infected cells. These
      data strongly validate Crm1 as a cellular cofactor for HIV-1 Rev and demonstrate
      that the MPMV CTE nuclear RNA export pathway uses a distinct, Crm1-independent
      mechanism. In addition, these data identify a novel and highly potent inhibitor
      of leucine-rich NES-dependent nuclear export.

PMID- 9765405
TI  - Potential contributions of viral envelope and host genetic factors in a human
      immunodeficiency virus type 1-infected long-term survivor.
AB  - The lack of clinical progression in some individuals despite prolonged human
      immunodeficiency virus type 1 (HIV-1) infection may result from infection with
      less-pathogenic viral strains. To address this question, we examined the HIV-1
      envelope protein from a donor with a low viral burden, stable CD4(+) T-lymphocyte
      counts, and little evidence of CD8(+) T-cell expansion, activation, or immune
      activity. To avoid potential changes in envelope function resulting from
      selection in vitro, envelope clones were constructed by using viral RNA isolated
      from uncultured peripheral blood mononuclear cells (PBMC). The data showed that
      recombinant viruses containing envelope sequences derived from RNA isolated from
      patient PBMC replicated poorly in primary CD4(+) T cells but demonstrated
      efficient growth in macrophages. The unusual phenotype of these viruses could not
      be explained solely by differential utilization of coreceptors since the chimeric
      viruses, as well as an uncloned isolate obtained from the same visit date, can
      utilize CCR5. In addition, the donor's own cells appeared resistant to infection
      with chimeric viruses containing autologous envelope sequences. Genotype analysis
      revealed that the donor was heterozygous for the previously described 32-bp
      deletion in CCR5 which may be linked with prolonged survival in HIV-1-infected
      individuals. These data suggest that the changes in envelope sequences confer
      properties of viral attenuation, which together with the CCR5 +/Delta32 genotype
      could account for the long-term survival of this patient.

PMID- 9765407
TI  - Interactions of soluble recombinant integrin alphav beta5 with human
      adenoviruses.
AB  - alphav integrins have been identified as coreceptors for adenovirus (Ad)
      internalization; however, direct interactions of these molecules with Ad have not
      been demonstrated. We report here the expression of soluble integrin alphav
      beta5, which retains the ability to recognize the Ad penton base as well as
      vitronectin, an Arg Gly Asp (RGD)-containing extracellular matrix protein.
      Soluble integrin alphav beta5 reacted with seven different Ad serotypes
      (subgroups A to E) in solid-phase binding assays. The soluble integrin exhibited
      different levels of binding to each Ad serotype; however, binding to multiple Ad
      types required the presence of divalent metal cations and was inhibited by a
      synthetic RGD peptide, indicating that RGD and cation-binding sequences regulate
      Ad interactions with alphav beta5. Incubation of Ad particles with soluble alphav
      beta5 integrin also inhibited subsequent Ad internalization into epithelial cells
      as well as virus attachment to monocytic cells. These findings suggest that
      soluble alphav integrins or antagonists of these coreceptors could be used to
      limit infection by multiple Ad types. The generation of soluble alphav integrins
      should also permit further detailed kinetic and structural analysis of Ad
      interactions with its coreceptors.

PMID- 9765406
TI  - Multimer formation is not essential for nuclear export of human T-cell leukemia
      virus type 1 Rex trans-activator protein.
AB  - The Rex trans-regulatory protein of human T-cell leukemia virus type 1 (HTLV-1)
      is required for the nuclear export of incompletely spliced and unspliced viral
      mRNAs and is therefore essential for virus replication. Rex is a nuclear
      phosphoprotein that directly binds to its cis-acting Rex response element RNA
      target sequence and constantly shuttles between the nucleus and cytoplasm.
      Moreover, Rex induces nuclear accumulation of unspliced viral RNA. Three protein
      domains which mediate nuclear import-RNA binding, nuclear export, and Rex
      oligomerization have been mapped within the 189-amino-acid Rex polypeptide. Here
      we identified a different region in the carboxy-terminal half of Rex which is
      also required for biological activity. In inactive mutants with mutations that
      map within this region, as well as in mutants that are deficient in Rex-specific
      multimerization, Rex trans activation could be reconstituted by fusion to a
      heterologous leucine zipper dimerization interface. The intracellular trafficking
      capabilities of wild-type and mutant Rex proteins reveal that biologically
      inactive and multimerization-deficient Rex mutants are still efficiently
      translocated from the nucleus to the cytoplasm. This observation indicates that
      multimerization is essential for Rex function but is not required for nuclear
      export. Finally, we are able to provide an improved model of the HTLV-1 Rex
      domain structure.

PMID- 9765408
TI  - Synthetic DNA replication bubbles bound and unwound with twofold symmetry by a
      simian virus 40 T-antigen double hexamer.
AB  - Dimerization of simian virus 40 T-antigen hexamers (TAgH) into double hexamers
      (TAgDH) on model DNA replication forks has been found to greatly stimulate T
      antigen DNA helicase activity. To explore the interaction of TAgDH with DNA
      during unwinding, we examined the binding of TAgDH to synthetic DNA replication
      bubbles. Tests of replication bubble substrates containing different single
      stranded DNA (ssDNA) lengths indicated that efficient formation of a TAgDH
      requires >/=40 nucleotides (nt) of ssDNA. DNase I probing of a substrate
      containing a 60-nt ssDNA bubble complexed with a TAgDH revealed that T antigen
      bound the substrate with twofold symmetry. The strongest protection was observed
      over the 5' junction on each strand, with 5 bp of duplex DNA and approximately 17
      nt of adjacent ssDNA protected from nuclease cleavage. Stimulation of the T
      antigen DNA helicase activity by an increase in ATP concentration caused the
      protection to extend in the 5' direction into the duplex region, while resulting
      in no significant changes to the 3' edge of strongest protection. Our data
      indicate that each TAgH encircles one ssDNA strand, with a different strand bound
      at each junction. The process of DNA unwinding results in each TAgH interacting
      with a greater length of DNA than was initially bound, suggesting the generation
      of a more highly processive helicase complex.

PMID- 9765409
TI  - Human cytotoxic T-lymphocyte repertoire to influenza A viruses.
AB  - The murine CD8(+) cytotoxic-T-lymphocyte (CTL) repertoire appears to be quite
      limited in response to influenza A viruses. The CTL responses to influenza A
      virus in humans were examined to determine if the CTL repertoire is also very
      limited. Bulk cultures revealed that a number of virus proteins were recognized
      in CTL assays. CTL lines were isolated from three donors for detailed study and
      found to be specific for epitopes on numerous influenza A viral proteins. Eight
      distinct CD8(+) CTL lines were isolated from donor 1. The proteins recognized by
      these cell lines included the nucleoprotein (NP), matrix protein (M1),
      nonstructural protein 1 (NS1), polymerases (PB1 and PB2), and hemagglutinin (HA).
      Two CD4(+) cell lines, one specific for neuraminidase (NA) and the other specific
      for M1, were also characterized. These CTL results were confirmed by precursor
      frequency analysis of peptide-specific gamma interferon-producing cells detected
      by ELISPOT. The epitopes recognized by 6 of these 10 cell lines have not been
      previously described; 8 of the 10 cell lines were cross-reactive to subtype H1N1,
      H2N2, and H3N2 viruses, 1 cell line was cross-reactive to subtypes H1N1 and H2N2,
      and 1 cell line was subtype H1N1 specific. A broad CTL repertoire was detected in
      the two other donors, and cell lines specific for the NP, NA, HA, M1, NS1, and M2
      viral proteins were isolated. These findings indicate that the human memory CTL
      response to influenza A virus is broadly directed to epitopes on a wide variety
      of proteins, unlike the limited response observed following infection of mice.

PMID- 9765410
TI  - Measles virus attenuation associated with transcriptional impediment and a few
      amino acid changes in the polymerase and accessory proteins.
AB  - Measles virus (MV) isolated in B95a cells, a marmoset B-cell line, retains full
      pathogenicity for cynomolgus monkeys, while its derivative obtained by adaptation
      to the growth in Vero cells, a monkey kidney cell line, loses the pathogenic
      potential (F. Kobune, H. Sakata, and A. Sugiura, J. Virol. 64:700-705, 1990).
      Here, we show with a pair of strains, a fresh isolate (9301B) in B95a cells and
      its Vero cell-adapted form (9301V), that the in vivo attenuation parallels the
      decrease of replication and syncytium-inducing capabilities in the original B95a
      cells and that these in vitro phenotypes are attributable to impediment of
      transcription, which is already obvious at the level of primary transcription
      catalyzed by the virion-associated RNA polymerase. On the other hand, cell fusion
      assays detected no functional difference between the glycoproteins of the two
      viruses. Essentially the same transcriptional impediment with reduced syncytium
      induction following Vero cell adaptation was found with two other pairs of
      strains that had been similarly prepared. Nucleotide sequence comparison between
      the 9301B and 9301V viruses revealed that a few (at most five) amino acid
      changes, which sporadically took place in the polymerase (L and P proteins)
      and/or accessory V and C proteins, were responsible for the in vitro and in vivo
      attenuation through adaptation to growth in Vero cells.

PMID- 9765411
TI  - Ribosomal S27a coding sequences upstream of ubiquitin coding sequences in the
      genome of a pestivirus.
AB  - Molecular characterization of cytopathogenic (cp) bovine viral diarrhea virus
      (BVDV) strain CP Rit, a temperature-sensitive strain widely used for vaccination,
      revealed that the viral genomic RNA is about 15.2 kb long, which is about 2.9 kb
      longer than the one of noncytopathogenic (noncp) BVDV strains. Molecular cloning
      and nucleotide sequencing of parts of the genome resulted in the identification
      of a duplication of the genomic region encoding nonstructural proteins NS3, NS4A,
      and part of NS4B. In addition, a nonviral sequence was found directly upstream of
      the second copy of the NS3 gene. The 3' part of this inserted sequence encodes an
      N-terminally truncated ubiquitin monomer. This is remarkable since all described
      cp BVDV strains with ubiquitin coding sequences contain at least one complete
      ubiquitin monomer. The 5' region of the nonviral sequence did not show any
      homology to cellular sequences identified thus far in cp BVDV strains. Databank
      searches revealed that this second cellular insertion encodes part of ribosomal
      protein S27a. Further analyses included molecular cloning and nucleotide
      sequencing of the cellular recombination partner. Sequence comparisons strongly
      suggest that the S27a and the ubiquitin coding sequences found in the genome of
      CP Rit were both derived from a bovine mRNA encoding a hybrid protein with the
      structure NH2-ubiquitin-S27a-COOH. Polyprotein processing in the genomic region
      encoding the N-terminal part of NS4B, the two cellular insertions, and NS3 was
      studied by a transient-expression assay. The respective analyses showed that the
      S27a-derived polypeptide, together with the truncated ubiquitin, served as
      processing signal to yield NS3, whereas the truncated ubiquitin alone was not
      capable of mediating the cleavage. Since the expression of NS3 is strictly
      correlated with the cp phenotype of BVDV, the altered genome organization leading
      to expression of NS3 most probably represents the genetic basis of
      cytopathogenicity of CP Rit.

PMID- 9765413
TI  - Infection of ducklings with virus particles containing linear double-stranded
      duck hepatitis B virus DNA: illegitimate replication and reversion.
AB  - Double-stranded linear DNA is synthesized as a minor viral DNA species by all
      hepadnaviruses. In a previous study (W. Yang and J. Summers, J. Virol. 69:4029
      4036, 1995) we showed that virus particles containing linear DNA of the duck
      hepatitis B virus (DHBV) could initiate an infection of primary duck hepatocytes.
      In cells infected by linear DNA containing viruses the transcriptional template,
      covalently closed circular DNA, was formed by circularization of linear DNA by
      nonhomologous recombination between the two ends. This process was shown to
      result in viral DNA replication through multiple generations of linear DNA
      intermediates, a process we called illegitimate replication. In this study we
      showed that viruses containing linear DHBV DNA produced by engineered insertions
      in the r sequence, which encodes the 5' end of the pregenome, could infect
      hepatocytes in vivo, and these hepatocytes proceeded to carry out illegitimate
      replication. Nonhomologous recombination quickly produced revertants and partial
      revertants in which all or part of the insertion was deleted. One such partial
      revertant that replicated primarily through circular DNA intermediates, but which
      synthesized elevated levels of linear DNA, could be sustained for several days as
      the predominant genotype in vivo, but this mutant was eventually displaced by
      variants showing full reversion to legitimate replication and that synthesized
      normal low levels of linear DNA. Full revertants did not necessarily contain the
      wild-type r sequence. The results suggest that the linear DNA produced during
      DHBV infection initiates cycles of illegitimate replication by generating mutants
      with altered r sequences. Some r sequence mutants carry out a mixture of
      legitimate and illegitimate replication that can contribute to elevated
      production of linear DNA in individual cells.

PMID- 9765412
TI  - The molecular chaperone calnexin interacts with the NSP4 enterotoxin of rotavirus
      in vivo and in vitro.
AB  - Calnexin is an endoplasmic reticulum (ER)-associated molecular chaperone proposed
      to promote folding and assembly of glycoproteins that traverse the secretory
      pathway in eukaryotic cells. In this study we examined if calnexin interacts with
      the ER-associated luminal (VP7) and transmembrane (NSP4) proteins of rotavirus.
      Only glycosylated NSP4 interacted with calnexin and did so in a time-dependent
      manner (half-life, 20 min). In vitro translation experiments programmed with gene
      10 of rhesus rotavirus confirmed that calnexin recognizes only glycosylated NSP4.
      Castanospermine (a glucosidase I and II inhibitor) experiments established that
      calnexin associates only with partly deglucosylated (di- or monoglucosylated)
      NSP4. Furthermore, enzymatic removal of the remaining glucose residues on the N
      linked glycan units was essential to disengage the NSP4-calnexin complex. Novel
      experiments with castanospermine revealed that glucose trimming and the calnexin
      NSP4 interaction were not critical for the assembly of infectious virus.

PMID- 9765414
TI  - Proteolytic processing and assembly of gag and gag-pol proteins of TED, a
      baculovirus-associated retrotransposon of the gypsy family.
AB  - TED (transposable element D) is an env-containing member of the gypsy family of
      retrotransposons that represents a possible retrovirus of invertebrates. This
      lepidopteran (moth) retroelement contains gag and pol genes that encode proteins
      capable of forming viruslike particles (VLP) with reverse transcriptase. Since
      VLP are likely intermediates in TED transposition, we investigated the roles of
      gag and pol in TED capsid assembly and maturation. By using constructed
      baculovirus vectors and TED Gag-specific antiserum, we show that the principal
      translation product of gag (Pr55(gag)) is cleaved to produce a single VLP
      structural protein, p37(gag). Replacement of Asp436 within the retrovirus-like
      active site of the pol-encoded protease (PR) abolished Pr55(gag) cleavage and
      demonstrated the requirement for PR in capsid processing. As shown by expression
      of an in-frame fusion of TED gag and pol, PR is derived from the Gag-Pol
      polyprotein Pr195(gag-pol). The PR cleavage site within Pr55(gag) was mapped to a
      position near the junction of a basic, nucleocapsid-like domain and a C-terminal
      acidic domain. Once released by cleavage, the C-terminal fragment was not
      detected. This acidic fragment was dispensable for VLP assembly, as demonstrated
      by the formation of VLP by C-terminal Pr55(gag) truncation proteins and
      replacement of the acidic domain with a heterologous protein. In contrast, C
      terminal deletions that extended into the adjacent nucleocapsid-like domain of
      Pr55(gag) abolished VLP recovery and demonstrated that this central region
      contributes to VLP assembly or stability, or both. Collectively, these data
      suggest that the single TED protein p37(gag) provides both capsid and
      nucleocapsid functions. TED may therefore use a simple processing strategy for
      VLP assembly and genome packaging.

PMID- 9765415
TI  - Definition and distribution analysis of glycoprotein B gene alleles of human
      herpesvirus 7.
AB  - As for other herpesviruses, glycoprotein B (gB) of human herpesvirus 7 (HHV-7) is
      believed to play a major role in virus infection and as a target of the host
      immunogenic response. Using nested PCR, we amplified the whole HHV-7 gB gene from
      108 human peripheral blood mononuclear cell samples and studied its variability.
      By means of restriction fragment length polymorphism (RFLP) analysis, three
      distinct patterns, designated I, II, and III, were defined and detected at
      frequencies of 93, 5, and 2%, respectively. Determination of the nucleotide
      sequence allowed us to recognize five critical positions in the gB gene with six
      specific combinations of point changes at these positions. These combinations
      were gB alleles A, B, C, D, E, and F. Alleles D and E corresponded to RFLP
      patterns II and III, respectively, while the other four alleles corresponded to
      RFLP pattern I. Identical gB alleles were detected in serial samples as well as
      in paired samples of blood and saliva from the same individuals, except for one
      case. In contrast, the distribution of gB alleles differed according to the
      geographical origin of the human samples: C was the most frequent allele in both
      African and Caribbean samples, whereas F was the most frequent allele in European
      ones. Although none of the allele-specific nucleotide changes induced any
      modification at the protein level, the definition of gB alleles provided
      convenient viral markers for the study of both HHV-7 infections and human
      population genetics.

PMID- 9765416
TI  - Isolation of an Arabidopsis thaliana mutant in which the multiplication of both
      cucumber mosaic virus and turnip crinkle virus is affected.
AB  - During the systemic infection of plants by viruses, host factors play an
      important role in supporting virus multiplication. To identify and characterize
      the host factors involved in this process, we isolated an Arabidopsis thaliana
      mutant named RB663, in which accumulation of the coat protein (CP) of cucumber
      mosaic virus (CMV) in upper uninoculated leaves was delayed. Genetic analyses
      suggested that the phenotype of delayed accumulation of CMV CP in RB663 plants
      was controlled by a monogenic, recessive mutation designated cum2-1, which is
      located on chromosome III and is distinct from the previously characterized cum1
      mutation. Multiplication of CMV was delayed in inoculated leaves of RB663 plants,
      whereas the multiplication in RB663 protoplasts was similar to that in wild-type
      protoplasts. This suggests that the cum2-1 mutation affects the cell-to-cell
      movement of CMV rather than CMV replication within a single cell. In RB663
      plants, the multiplication of turnip crinkle virus (TCV) was also delayed but
      that of tobacco mosaic virus was not affected. As observed with CMV, the
      multiplication of TCV was normal in protoplasts and delayed in inoculated leaves
      of RB663 plants compared to that in wild-type plants. Furthermore, the phenotype
      of delayed TCV multiplication cosegregated with the cum2-1 mutation as far as we
      examined. Therefore, the cum2-1 mutation is likely to affect the cell-to-cell
      movement of both CMV and TCV, implying a common aspect to the mechanisms of cell
      to-cell movement in these two distinct viruses.

PMID- 9765417
TI  - Specific encapsidation of nodavirus RNAs is mediated through the C terminus of
      capsid precursor protein alpha.
AB  - Flock house virus (FHV) is a small icosahedral insect virus with a bipartite,
      messenger-sense RNA genome. Its T=3 icosahedral capsid is initially assembled
      from 180 subunits of a single type of coat protein, capsid precursor protein
      alpha (407 amino acids). Following assembly, the precursor particles undergo a
      maturation step in which the alpha subunits autocatalytically cleave between
      Asn363 and Ala364. This cleavage generates mature coat proteins beta (363
      residues) and gamma (44 residues) and is required for acquisition of virion
      infectivity. The X-ray structure of mature FHV shows that gamma peptides located
      at the fivefold axes of the virion form a pentameric helical bundle, and it has
      been suggested that this bundle plays a role in release of viral RNA during FHV
      uncoating. To provide experimental support for this hypothesis, we generated
      mutant coat proteins that carried deletions in the gamma region of precursor
      protein alpha. Surprisingly, we found that these mutations interfered with
      specific recognition and packaging of viral RNA during assembly. The resulting
      particles contained large amounts of cellular RNAs and varying amounts of the
      viral RNAs. Single-site amino acid substitution mutants showed that three
      phenylalanines located at positions 402, 405, and 407 of coat precursor protein
      alpha were critically important for specific recognition of the FHV genome. Thus,
      in addition to its hypothesized role in uncoating and RNA delivery, the C
      terminal region of coat protein alpha plays a significant role in recognition of
      FHV RNA during assembly. A possible link between these two functions is
      discussed.

PMID- 9765418
TI  - Effects of mutations in the rubella virus E1 glycoprotein on E1-E2 interaction
      and membrane fusion activity.
AB  - Rubella virus (RV) virions contain two glycosylated membrane proteins, E1 and E2,
      that exist as a heterodimer and form the viral spike complexes on the virion
      surface. Formation of an E1-E2 heterodimer is required for transport of E1 out of
      the endoplasmic reticulum lumen to the Golgi apparatus and plasma membrane. To
      investigate the nature of the E1-E2 interaction, we have introduced mutations in
      the internal hydrophobic region (residues 81 to 109) of E1. Substitution of
      serine at Cys82 (mutant C82S) or deletion of this hydrophobic domain (mutant dt)
      of E1 resulted in a disruption of the E1 conformation that ultimately affected E1
      E2 heterodimer formation and cell surface expression of both E1 and E2.
      Substitution of either aspartic acid at Gly93 (G93D) or glycine at Pro104 (P104G)
      was found to impair neither E1-E2 heterodimer formation nor the transport of E1
      and E2 to the cell surface. Fusion of RV-infected cells is induced by a brief
      treatment at a pH below 6. 0. To test whether this internal hydrophobic domain is
      involved in the membrane fusion activity of RV, transformed BHK cell lines
      expressing either wild-type or mutant spike proteins were exposed to an acidic pH
      and polykaryon formation was measured. No fusion activity was observed in the
      C82S, dt, and G93D mutants; however, the wild type and the P104G mutant exhibited
      fusogenic activities, with greater than 60% and 20 to 40% of the cells being
      fused, respectively, at pH 4.8. These results suggest that it is likely that the
      region of E1 between amino acids 81 and 109 is involved in the membrane fusion
      activity of RV and that it may be important for the interaction of that protein
      with E2 to form the E1-E2 heterodimer.

PMID- 9765419
TI  - Three of the four nucleocapsid proteins of Marburg virus, NP, VP35, and L, are
      sufficient to mediate replication and transcription of Marburg virus-specific
      monocistronic minigenomes.
AB  - This paper describes the first reconstituted replication system established for a
      member of the Filoviridae, Marburg virus (MBGV). MBGV minigenomes containing the
      leader and trailer regions of the MBGV genome and the chloramphenicol
      acetyltransferase (CAT) gene were constructed. In MBGV-infected cells, these
      minigenomes were replicated and encapsidated and could be passaged. Unlike most
      other members of the order Mononegavirales, filoviruses possess four proteins
      presumed to be components of the nucleocapsid (NP, VP35, VP30, and L). To
      determine the protein requirements for replication and transcription, a reverse
      genetic system was established for MBGV based on the vaccinia virus T7 expression
      system. Northern blot analysis of viral RNA revealed that three nucleocapsid
      proteins (NP, VP35, and L) were essential and sufficient for transcription as
      well as replication and encapsidation. These data indicate that VP35, rather than
      VP30, is the functional homologue of rhabdo- and paramyxovirus P proteins. The
      reconstituted replication system was profoundly affected by the NP-to-VP35
      expression ratio. To investigate whether CAT gene expression was achieved
      entirely by mRNA or in part by full-length plus-strand minigenomes, a copy-back
      minireplicon containing the CAT gene but lacking MBGV-specific transcriptional
      start sites was employed in the artificial replication system. This construct was
      replicated without accompanying CAT activity. It was concluded that the CAT
      activity reflected MBGV-specific transcription and not replication.

PMID- 9765420
TI  - Walleye retroviruses associated with skin tumors and hyperplasias encode cyclin D
      homologs.
AB  - Walleye dermal sarcoma (WDS) and walleye epidermal hyperplasia (WEH) are skin
      diseases of walleye fish that appear and regress on a seasonal basis. We report
      here that the complex retroviruses etiologically associated with WDS (WDS virus
      [WDSV]) and WEH (WEH viruses 1 and 2 [WEHV1 and WEHV2, respectively]) encode D
      type cyclin homologs. The retroviral cyclins (rv-cyclins) are distantly related
      to one another and to known cyclins and are not closely related to any walleye
      cellular gene based on low-stringency Southern blotting. Since aberrant
      expression of D-type cyclins occurs in many human tumors, we suggest that
      expression of the rv-cyclins may contribute to the development of WDS or WEH. In
      support of this hypothesis, we show that rv-cyclin transcripts are made in
      developing WDS and WEH and that the rv-cyclin of WDSV induces cell cycle
      progression in yeast (Saccharomyces cerevisiae). WEHV1, WEHV2, and WDSV are the
      first examples of retroviruses that encode cyclin homologs. WEH and WDS and their
      associated retroviruses represent a novel paradigm of retroviral tumor induction
      and, importantly, tumor regression.

PMID- 9765422
TI  - Heterogeneous nuclear ribonucleoprotein L interacts with the 3' border of the
      internal ribosomal entry site of hepatitis C virus.
AB  - Translation initiation of hepatitis C virus (HCV) RNA occurs by internal entry of
      a ribosome into the 5' nontranslated region in a cap-independent manner. The HCV
      RNA sequence from about nucleotide 40 up to the N terminus of the coding sequence
      of the core protein is required for efficient internal initiation of translation,
      though the precise border of the HCV internal ribosomal entry site (IRES) has yet
      to be determined. Several cellular proteins have been proposed to direct HCV IRES
      dependent translation by binding to the HCV IRES. Here we report on a novel
      cellular protein that specifically interacts with the 3' border of the HCV IRES
      in the core-coding sequence. This protein with an apparent molecular mass of 68
      kDa turned out to be heterogeneous nuclear ribonucleoprotein L (hnRNP L). The
      binding of hnRNP L to the HCV IRES correlates with the translational efficiencies
      of corresponding mRNAs. This finding suggests that hnRNP L may play an important
      role in the translation of HCV mRNA through the IRES element.

PMID- 9765421
TI  - In vitro processing of herpes simplex virus type 1 DNA replication intermediates
      by the viral alkaline nuclease, UL12.
AB  - Herpes simplex virus type 1 (HSV-1) DNA replication intermediates exist in a
      complex nonlinear structure that does not migrate into a pulsed-field gel.
      Genetic evidence suggests that the product of the UL12 gene, termed alkaline
      nuclease, plays a role in processing replication intermediates (R. Martinez, R.
      T. Sarisky, P. C. Weber, and S. K. Weller, J. Virol. 70:2075-2085, 1996). In this
      study we have tested the hypothesis that alkaline nuclease acts as a structure
      specific resolvase. Cruciform structures generated with oligonucleotides were
      treated with purified alkaline nuclease; however, instead of being resolved into
      linear duplexes as would be expected of a resolvase activity, the artificial
      cruciforms were degraded. DNA replication intermediates were isolated from the
      well of a pulsed-field gel ("well DNA") and treated with purified HSV-1 alkaline
      nuclease. Although alkaline nuclease can degrade virion DNA to completion,
      digestion of well DNA results in a smaller-than-unit-length product that migrates
      as a heterogeneous smear; this product is resistant to further digestion by
      alkaline nuclease. The smaller-than-unit-length products are representative of
      the entire HSV genome, indicating that alkaline nuclease is not inhibited at
      specific sequences. To further probe the structure of replicating DNA, well DNA
      was treated with various known nucleases; our results indicate that replicating
      DNA apparently contains no accessible double-stranded ends but does contain nicks
      and gaps. Our data suggest that UL12 functions at nicks and gaps in replicating
      DNA to correctly repair or process the replicating genome into a form suitable
      for encapsidation.

PMID- 9765423
TI  - The 3'-untranslated region of hepatitis C virus RNA enhances translation from an
      internal ribosomal entry site.
AB  - Translation of most eukaryotic mRNAs and many viral RNAs is enhanced by their
      poly(A) tails. Hepatitis C virus (HCV) contains a positive-stranded RNA genome
      which does not have a poly(A) tail but has a stretch of 98 nucleotides (X region)
      at the 3'-untranslated region (UTR), which assumes a highly conserved stem-loop
      structure. This X region binds a polypyrimidine tract-binding protein (PTB),
      which also binds to the internal ribosome entry site (IRES) in HCV 5'-UTR. These
      RNA-protein interactions may regulate its translation. We generated a set of HCV
      RNAs differing only in their 3'-UTRs and compared their translation efficiencies.
      HCV RNA containing the X region was translated three- to fivefold more than the
      corresponding RNAs without this region. Mutations that abolished PTB binding in
      the X region reduced, but did not completely abolish, enhancement in translation.
      The X region also enhanced translation from another unrelated IRES (from
      encephalomyocarditis virus RNA), but did not affect the 5'-end-dependent
      translation of globin mRNA in either monocistronic or bicistronic RNAs. It did
      not appear to affect RNA stability. The free X region added in trans, however,
      did not enhance translation, indicating that the translational enhancement by the
      X region occurs only in cis. These results demonstrate that the highly conserved
      3' end of HCV RNA provides a novel mechanism for enhancement of HCV translation
      and may offer a target for antiviral agents.

PMID- 9765424
TI  - CD4 promoter transactivation by human herpesvirus 6.
AB  - The observation that human herpesvirus 6 (HHV-6) can induce CD4 gene
      transcription and expression in CD4(-) cells was reported several years ago (P.
      Lusso, A. De Maria, M. Malnati, F. Lori, S. E. DeRocco, M. Baseler, and R. C.
      Gallo, Nature 349:533-535, 1991) and subsequently confirmed (P. Lusso, M. S.
      Malnati, A. Garzino-Demo, R. W. Crowley, E. O. Long, and R. C. Gallo, Nature
      362:458-462, 1993; G. Furlini, M. Vignoli, E. Ramazzotti, M. C. Re, G. Visani,
      and M. LaPlaca, Blood 87:4737-4745, 1996). Our objective was to identify the
      mechanisms underlying such phenomena. Using reporter gene constructs driven by
      the CD4 promoter, we report that HHV-6 can efficiently transactivate such genetic
      elements. Activation of the CD4 promoter occurs in the presence of the viral DNA
      polymerase inhibitor phosphonoformic acid, which limits expression to the
      immediate-early and early classes of viral genes. Using deletion mutants and
      specific CD4 promoter mutants, we identified an ATF/CRE binding site located at
      nucleotides -67 to -60 upstream of the CD4 gene transcription start site that is
      important for HHV-6 transactivation. The ATF/CRE site is also essential for CD4
      promoter activation by forskolin, an activator of adenylate cyclase. Using
      electrophoretic mobility shift assays and specific antibodies, we showed that
      CREB-1 binds specifically to the -79 to -52 region of the CD4 promoter. Last, we
      have identified two open reading frames (ORFs) of HHV-6, U86 and U89 from the
      immediate-early locus A, that can transactivate the CD4 promoter in HeLa cells.
      However, transactivation of the CD4 promoter by ORFs U86 and U89 is independent
      of the CRE element, suggesting that additional HHV-6 ORFs are likely to
      contribute to CD4 gene activation. Taken together, our results will help to
      understand the complex interactions occurring between HHV-6 and the CD4 promoter
      and provide additional information regarding the class of transcription factors
      involved in the control of CD4 gene expression.

PMID- 9765425
TI  - Adenovirus endocytosis requires actin cytoskeleton reorganization mediated by Rho
      family GTPases.
AB  - Adenovirus (Ad) endocytosis via alphav integrins requires activation of the lipid
      kinase phosphatidylinositol-3-OH kinase (PI3K). Previous studies have linked PI3K
      activity to both the Ras and Rho signaling cascades, each of which has the
      capacity to alter the host cell actin cytoskeleton. Ad interaction with cells
      also stimulates reorganization of cortical actin filaments and the formation of
      membrane ruffles (lamellipodia). We demonstrate here that members of the Rho
      family of small GTP binding proteins, Rac and CDC42, act downstream of PI3K to
      promote Ad endocytosis. Ad internalization was significantly reduced in cells
      treated with Clostridium difficile toxin B and in cells expressing a dominant
      negative Rac or CDC42 but not a H-Ras protein. Viral endocytosis was also
      inhibited by cytochalasin D as well as by expression of effector domain mutants
      of Rac or CDC42 that impair cytoskeletal function but not JNK/MAP kinase pathway
      activation. Thus, Ad endocytosis requires assembly of the actin cytoskeleton, an
      event initiated by activation of PI3K and, subsequently, Rac and CDC42.

PMID- 9765426
TI  - Vaccinia virus protein synthesis has a low requirement for the intact translation
      initiation factor eIF4F, the cap-binding complex, within infected cells.
AB  - The role of the cap-binding complex, eIF4F, in the translation of vaccinia virus
      mRNAs has been analyzed within infected cells. Plasmid DNAs, which express
      dicistronic mRNAs containing a picornavirus internal ribosome entry site,
      produced within vaccinia virus-infected cells both beta-glucuronidase and a cell
      surface-targeted single-chain antibody (sFv). Cells expressing sFv were selected
      from nonexpressing cells, enabling analysis of protein synthesis specifically
      within the transfected cells. Coexpression of poliovirus 2A or foot-and-mouth
      disease virus Lb proteases, which cleaved translation initiation factor eIF4G,
      greatly inhibited cap-dependent protein (beta-glucuronidase) synthesis. Under
      these conditions, internal ribosome entry site-directed expression of sFv
      continued and cell selection was maintained. Furthermore, vaccinia virus protein
      synthesis persisted in the selected cells containing cleaved eIF4G. Thus, late
      vaccinia virus protein synthesis has a low requirement for the intact cap-binding
      complex eIF4F. This may be attributed to the short unstructured 5' noncoding
      regions of the vaccinia virus mRNAs, possibly aided by the presence of poly(A) at
      both 5' and 3' termini.

PMID- 9765428
TI  - Virion incorporation of human immunodeficiency virus type 1 Nef is mediated by a
      bipartite membrane-targeting signal: analysis of its role in enhancement of viral
      infectivity.
AB  - The nef gene of primate immunodeficiency viruses is essential for high-titer
      virus replication and AIDS pathogenesis in vivo. In tissue culture, Nef is not
      required for human immunodeficiency virus (HIV) infection but enhances viral
      infectivity. We and others have shown that Nef is incorporated into HIV-1
      particles and cleaved by the viral proteinase. To determine the signal for Nef
      incorporation and to analyze whether virion-associated Nef is responsible for
      enhancement of infectivity, we generated a panel of nef mutants and analyzed them
      for virion incorporation of Nef and for their relative infectivities. We report
      that N-terminal truncations of Nef abolished its incorporation into HIV
      particles. Incorporation was reconstituted by targeting the respective proteins
      to the plasma membrane by using a heterologous signal. Mutational analysis
      revealed that both myristoylation and an N-terminal cluster of basic amino acids
      were required for virion incorporation and for plasma membrane targeting of Nef.
      Grafting the N-terminal anchor domain of Nef onto the green fluorescent protein
      led to membrane targeting and virion incorporation of the resulting fusion
      protein. These results indicate that Nef incorporation into HIV-1 particles is
      mediated by plasma membrane targeting via an N-terminal bipartite signal which is
      reminiscent of a Src homology region 4. Virion incorporation of Nef correlated
      with enhanced infectivity of the respective viruses in a single-round replication
      assay. However, the phenotypes of HIV mutants with reduced Nef incorporation only
      partly correlated with their ability to replicate in primary lymphocytes,
      indicating that additional or different mechanisms may be involved in this
      system.

PMID- 9765427
TI  - Rhesus macaques infected with macrophage-tropic simian immunodeficiency virus
      (SIVmacR71/17E) exhibit extensive focal segmental and global glomerulosclerosis.
AB  - We previously showed that inoculation of rhesus macaques with molecularly cloned
      lymphocytetropic simian immunodeficiency virus (SIVmac239) results in SIV
      associated nephropathy (SIVAN) and that the glomerulosclerotic lesions were
      associated with the selection of macrophagetropic (M-tropic) variants (V. H.
      Gattone et al., AIDS Res. Hum. Retroviruses 14:1163-1180, 1998). In the present
      study, seven rhesus macaques were inoculated with M-tropic SIVmacR71/17E, and the
      renal pathology was examined at necropsy. All SIVmacR71/17E-infected macaques
      developed AIDS, and most developed other systemic complications, including SIV
      induced encephalitis and lentivirus interstitial pneumonia. There was no
      correlation between the length of infection (42 to 97 days), circulating CD4(+) T
      cell counts, and renal disease. Of the seven macaques inoculated with
      SIVmacR71/17E, five developed significant mesangial hyperplasia and expansion of
      matrix and four were clearly azotemic (serum urea nitrogen concentration of 40 to
      112 mg/dl). These same five macaques developed focal segmental to global
      glomerulosclerotic lesions. Increased numbers of glomerular CD68(+) cells
      (monocytes/macrophages) were found in glomeruli but not the tubulointerstitium of
      the macaques inoculated with SIVmacR71/17E. All macaques had glomerular deposits
      of immunoglobulin G (IgG), IgM, and tubuloreticular inclusions, and six of seven
      had IgA deposition. However, there was no correlation between the presence of
      circulating anti-SIVmac antibodies, immunoglobulin deposition, and glomerular
      disease. Tubulointerstitial infiltrates were mild, with little or no correlation
      to azotemia, while microcystic tubules were evident in those with
      glomerulosclerosis or azotemia. The four most severely affected macaques were
      positive for diffuse glomerular immunostaining for viral core p27 antigen, and
      there was intense staining in the glomeruli of the two macaques with the most
      severe glomerulosclerosis. Viral sequences were isolated from glomerular and
      tubulointerstitial fractions from macaques with severe glomerulosclerosis but
      only from the tubulointerstitial compartment of those that did not develop
      glomerulosclerosis. Interviral recombinant viruses generated with env sequences
      isolated from glomeruli confirmed the M-tropic nature of the virus found in the
      glomeruli. The correlation between the increased number of CD68(+) cells
      (monocytes/macrophages) in the glomeruli, the localization of p27 antigen in the
      glomeruli, and the glomerular pathology confirms and extends our previous
      observations of an association between glomerular infection and infiltration by M
      tropic virus and SIVAN.

PMID- 9765429
TI  - Isolation and characterization of a neuropathogenic simian immunodeficiency virus
      derived from a sooty mangabey.
AB  - Transfusion of blood from a simian immunodeficiency virus (SIV)- and simian T
      cell lymphotropic virus-infected sooty mangabey (designated FGb) to rhesus and
      pig-tailed macaques resulted in the development of neurologic disease in addition
      to AIDS. To investigate the role of SIV in neurologic disease, virus was isolated
      from a lymph node of a pig-tailed macaque (designated PGm) and the cerebrospinal
      fluid of a rhesus macaque (designated ROn2) and passaged to additional macaques.
      SIV-related neuropathogenic effects were observed in 100% of the pig-tailed
      macaques inoculated with either virus. Lesions in these animals included
      extensive formation of SIV RNA-positive giant cells in the brain parenchyma and
      meninges. Based upon morphology, the majority of infected cells in both lymphoid
      and brain tissue appeared to be of macrophage lineage. The virus isolates
      replicated very well in pig-tailed and rhesus macaque peripheral blood
      mononuclear cells (PBMC) with rapid kinetics. Differential replicative abilities
      were observed in both PBMC and macrophage populations, with viruses growing to
      higher titers in pig-tailed macaque cells than in rhesus macaque cells. An
      infectious molecular clone of virus derived from the isolate from macaque PGm
      (PGm5.3) was generated and was shown to have in vitro replication characteristics
      similar to those of the uncloned virus stock. While molecular analyses of this
      virus revealed its similarity to SIV isolates from sooty mangabeys, significant
      amino acid differences in Env and Nef were observed. This virus should provide an
      excellent system for investigating the mechanism of lentivirus-induced neurologic
      disease.

PMID- 9765430
TI  - Human T-cell lymphotropic/leukemia virus type 1 Tax abrogates p53-induced cell
      cycle arrest and apoptosis through its CREB/ATF functional domain.
AB  - Human T-cell lymphotropic/leukemia virus type 1 (HTLV-1) transforms human T cells
      in vitro, and Tax, a potent transactivator of viral and cellular genes, plays a
      key role in cell immortalization. Tax activity is mediated by interaction with
      cellular transcription factors including members of the CREB/ATF family, the NF
      kappaB/c-Rel family, serum response factor, and the coactivators CREB binding
      protein-p300. Although p53 is usually not mutated in HTLV-1-infected T cells, its
      half-life is increased and its function is impaired. Here we report that
      transient coexpression of p53 and Tax results in the suppression of p53
      transcriptional activity. Expression of Tax abrogates p53-induced G1 arrest in
      the Calu-6 cell line and prevents the apoptosis induced by overexpressing p53 in
      the HeLa/Tat cell line. The Tax mutants M22 and G148V, which selectively activate
      the CREB/ATF pathway, exert these same biological effects on p53 function. In
      contrast, the NF-kappaB-active Tax mutant M47 has no effect on p53 activity in
      any of these systems. Consistent with the negative effect of Tax on p53, no
      activity on a p53-responsive promoter was observed upon transfection of HTLV-1
      infected T-cell lines. The p53 protein is expressed at high levels in the
      nucleus, and nuclear extracts of HTLV-1-infected T cells bind constitutively to a
      DNA oligonucleotide containing the p53 response element, indicating that Tax does
      not interfere with p53 binding to DNA. Tax is able to suppress the
      transactivation function of p53 in three different cell lines, and this
      suppression required Tax-mediated activation of the CREB/ATF, but not the NF
      kappaB/c-Rel, pathway. Tax and the active Tax mutants were able to abrogate the
      G1 arrest and apoptosis induced by p53, and this effect does not correlate with
      an altered localization of nuclear p53 or with the disruption of p53-DNA
      complexes. The suppression of p53 activity by Tax could be important in T-cell
      immortalization induced by HTLV-1.

PMID- 9765431
TI  - Effect of host modification and age on airway epithelial gene transfer mediated
      by a murine leukemia virus-derived vector.
AB  - To study retroviral gene transfer to airway epithelia, we used a transient
      transfection technique to generate high titers (approximately 10(9) infectious
      units/ml after concentration) of murine leukemia virus (MuLV)-derived vectors
      pseudotyped with the vesicular stomatitis virus envelope glycoprotein (VSV-G).
      Transformed (CFT1) and primary airway epithelial cells were efficiently
      transduced by a VSV-G-pseudotyped lacZ vector (HIT-LZ) in vitro. CFT1 cells and
      primary cystic fibrosis (CF) airway cell monolayers infected with a vector (HIT
      LCFSN) containing human CF transmembrane conductance regulator (CFTR) in the
      absence of selection expressed CFTR, as assessed by Western blot analysis, and
      exhibited functional correction of CFTR-mediated Cl- secretion. In vitro studies
      of persistence suggested that pseudotransduction was not a significant problem
      with our vector preparations. In a sulfur dioxide (SO2) inhalational injury
      model, bromodeoxyuridine (BrdU) incorporation rates were measured and found to
      exceed 50% in SO2-injured murine tracheal epithelium. HIT-LZ vector (multiplicity
      of infection of approximately 10) instilled into the SO2-injured tracheas of
      anesthetized mice transduced 6.1% +/- 1.3% of superficial airway cells in
      tracheas of weanling mice (3 to 4 weeks old; n = 10), compared to 1.4 +/- 0.9% in
      mice 5 weeks of age (n = 4) and 0.2% in mice older than 6 weeks (n = 15). No
      evidence for gene transfer following delivery of HIT-LZ to tracheas of either
      weanling or older mice not injured with SO2 was detected. Because only a small
      fraction of BrdU-labeled airway cells were transduced, we examined the stability
      of the vector. No significant loss of vector infectivity over intervals (2 h)
      paralleling those of in vivo protocols was detected in in vitro assays using CFT1
      cells. In summary, high-titer vectors permitted complementation of defective CFTR
      mediated Cl- transport in CF airway cells in vitro without selection and
      demonstrated that the age of the animal appeared to be a major factor affecting
      in vivo retroviral transduction efficiency.

PMID- 9765432
TI  - High-titer human immunodeficiency virus type 1-based vector systems for gene
      delivery into nondividing cells.
AB  - Previously we designed novel pseudotyped high-titer replication defective human
      immunodeficiency virus type 1 (HIV-1) vectors to deliver genes into nondividing
      cells (J. Reiser, G. Harmison, S. Kluepfel-Stahl, R. O. Brady, S. Karlsson, and
      M. Schubert, Proc. Natl. Acad. Sci. USA 93:15266-15271, 1996). Since then we have
      made several improvements with respect to the safety, flexibility, and efficiency
      of the vector system. A three-plasmid expression system is used to generate
      pseudotyped HIV-1 particles by transient transfection of human embryonic kidney
      293T cells with a defective packaging construct, a plasmid coding for a
      heterologous envelope (Env) protein, and a vector construct harboring a reporter
      gene such as neo, ShlacZ (encoding a phleomycin resistance/beta-galactosidase
      fusion protein), HSA (encoding mouse heat-stable antigen), or EGFP (encoding
      enhanced green fluorescent protein). The packaging constructs lack functional
      Vif, Vpr, and Vpu proteins and/or a large portion of the Env coding region as
      well as the 5' and 3' long terminal repeats, the Nef function, and the presumed
      packaging signal. Using G418 selection, we routinely obtained vector particles
      pseudotyped with the vesicular stomatitis virus G glycoprotein (VSV-G) with
      titers of up to 8 x 10(7) CFU/microgram of p24, provided that a functional Tat
      coding region was present in the vector. Vector constructs lacking a functional
      Tat protein yielded titers of around 4 x 10(6) to 8 x 10(6) CFU/microgram of p24.
      Packaging constructs with a mutation within the integrase (IN) core domain
      profoundly affected colony formation and expression of the reporter genes,
      indicating that a functional IN protein is required for efficient transduction.
      We explored the abilities of other Env proteins to allow formation of pseudotyped
      HIV-1 particles. The rabies virus and Mokola virus G proteins yielded high-titer
      infectious pseudotypes, while the human foamy virus Env protein did not. Using
      the improved vector system, we successfully transduced contact-inhibited primary
      human skin fibroblasts and postmitotic rat cerebellar neurons and cardiac
      myocytes, a process not affected by the lack of the accessory proteins.

PMID- 9765433
TI  - A functional role for neutralizing antibodies in Borna disease: influence on
      virus tropism outside the central nervous system.
AB  - Borna disease virus (BDV) is a negative-strand RNA virus that infects the central
      nervous systems (CNS) of warm-blooded animals and causes disturbances of movement
      and behavior. The basis for neurotropism remains poorly understood; however, the
      observation that the distribution of infectious virus in immunocompetent rats is
      different from that in immunoincompetent rats indicates a role for the immune
      system in BDV tropism: whereas in immunocompetent rats virus is restricted to the
      central, peripheral, and autonomic nervous systems, immunoincompetent rats also
      have virus in nonneural tissues. In an effort to examine the influence of the
      humoral immune response on BDV pathogenesis, we examined the effects of passive
      immunization with neutralizing antiserum in immunoincompetent rats. Serum
      transfer into immunoincompetent rats did not prevent persistent CNS infection but
      did result in restriction of virus to neural tissues. These results indicate that
      neutralizing antibodies may play a role in preventing generalized infection with
      BDV.

PMID- 9765435
TI  - Factors influencing adeno-associated virus-mediated gene transfer to human cystic
      fibrosis airway epithelial cells: comparison with adenovirus vectors.
AB  - Adeno-associated virus (AAV) vectors appear promising for use in gene therapy in
      cystic fibrosis (CF) patients, yet many features of AAV-mediated gene transfer to
      airway epithelial cells are not well understood. We compared the transduction
      efficiencies of AAV vectors and adenovirus (Ad) vectors in immortalized cell
      lines from CF patients and in nasal epithelial primary cultures from normal
      humans and CF patients. Similar dose-dependent relationships between the vector
      multiplicities of infection and the efficiencies of lacZ gene transfer were
      observed. However, levels of transduction for both Ad and recombinant AAV (rAAV)
      were significantly lower in the airway epithelial cell than in the control cell
      lines HeLa and HEK 293. Transduction efficiencies differed among cultured
      epithelial cell types, with poorly differentiated cells transducing more
      efficiently than well-differentiated cells. A time-dependent increase in gene
      expression was observed after infection for both vectors. For Ad, but not for
      AAV, this increase was dependent on prolonged incubation of cells with the
      vector. Furthermore, for rAAV (but not for rAd), the delay in maximal
      transduction could be abrogated by wild-type Ad helper infection. Thus, although
      helper virus is not required for maximal transduction, it increases the kinetics
      by which this is achieved. Expression of Ad E4 open reading frame 6 or addition
      of either hydroxyurea or camptothecin resulted in increased AAV transduction, as
      previously demonstrated for nonairway cells (albeit to lower final levels),
      suggesting that second-strand synthesis may not be the sole cause of inefficient
      transduction. Finally, the efficiency of AAV-mediated ex vivo gene transfer to
      lung cells was similar to that previously described for Ad vectors in that
      transduction was limited to regions of epithelial injury and preferentially
      targeted basal-like cells. These studies address the primary factors influencing
      rAAV infection of human airway cells and should impact successful gene delivery
      in CF patients.

PMID- 9765436
TI  - Generation of infectious pancreatic necrosis virus from cloned cDNA.
AB  - We developed a reverse genetics system for infectious pancreatic necrosis virus
      (IPNV), a prototype virus of the Birnaviridae family, with the use of plus
      stranded RNA transcripts derived from cloned cDNA. Full-length cDNA clones of the
      IPNV genome that contained the entire coding and noncoding regions of RNA
      segments A and B were constructed. Segment A encodes a 106-kDa precursor protein
      which is cleaved to yield mature VP2, nonstructural protease, and VP3 proteins,
      whereas segment B encodes the RNA-dependent RNA polymerase VP1. Plus-sense RNA
      transcripts of both segments were prepared by in vitro transcription of
      linearized plasmids with T7 RNA polymerase. Transfection of chinook salmon embryo
      (CHSE) cells with combined transcripts of segments A and B generated infectious
      IPNV particles 10 days posttransfection. Furthermore, a transfectant virus
      containing a genetically tagged sequence was generated to confirm the feasibility
      of this system. The presence and specificity of the recovered virus were
      ascertained by immunofluorescence staining of infected CHSE cells with rabbit
      anti-IPNV serum and by nucleotide sequence analysis. In addition, 3'-terminal
      sequence analysis of RNA from the recovered virus showed that extraneous
      nucleotides synthesized at the 3' end during in vitro transcription were
      precisely trimmed or excluded during replication, and hence these were not
      incorporated into the genome. An attempt was made to determine if RNA-dependent
      RNA polymerase of IPNV and infectious bursal disease virus (IBDV), another
      birnavirus, can support virus rescue in heterologous combinations. Thus, CHSE
      cells were transfected with transcripts derived from IPNV segment A and IBDV
      segment B and Vero cells were transfected with transcripts derived from IBDV
      segment A and IPNV segment B. In either case, no infectious IPNV or IBDV
      particles were generated even after a third passage in cell culture, suggesting
      that viral RNA-dependent RNA polymerase is species specific. However, the reverse
      genetics system for IPNV that we developed will greatly facilitate studies of
      viral replication and pathogenesis and the design of a new generation of live
      attenuated vaccines.

PMID- 9765434
TI  - Induction of programmed cell death by parvovirus H-1 in U937 cells: connection
      with the tumor necrosis factor alpha signalling pathway.
AB  - The human promonocytic cell line U937 undergoes apoptosis upon treatment with
      tumor necrosis factor alpha (TNF-alpha). This cell line has previously been shown
      to be very sensitive to the lytic effect of the autonomous parvovirus H-1.
      Parvovirus infection leads to the activation of the CPP32 ICE-like cysteine
      protease which cleaves the enzyme poly(ADP-ribose)polymerase and induces
      morphologic changes that are characteristic of apoptosis in a way that is similar
      to TNF-alpha treatment. This effect is also observed when the U937 cells are
      infected with a recombinant H-1 virus which expresses the nonstructural (NS)
      proteins but in which the capsid genes are replaced by a reporter gene,
      indicating that the induction of apoptosis can be assigned to the cytotoxic
      nonstructural proteins in this cell system. The c-Myc protein, which is
      overexpressed in U937 cells, is rapidly downregulated during infection, in
      keeping with a possible role of this product in mediating the apoptotic cell
      death induced by H-1 virus infection. Interestingly, four clones (designated RU)
      derived from the U937 cell line and selected for their resistance to H-1 virus
      (J. A. Lopez-Guerrero et al., Blood 89:1642-1653, 1997) failed to decrease c-Myc
      expression upon treatment with differentiation agents and also resisted the
      induction of cell death after TNF-alpha treatment. Our data suggest that the RU
      clones have developed defense strategies against apoptosis, either by their
      failure to downregulate c-Myc and/or by activating antiapoptotic factors.

PMID- 9765437
TI  - Role of glutamine 17 of the bovine papillomavirus E5 protein in platelet-derived
      growth factor beta receptor activation and cell transformation.
AB  - The bovine papillomavirus E5 protein is a small, homodimeric transmembrane
      protein that forms a stable complex with the cellular platelet-derived growth
      factor (PDGF) beta receptor through transmembrane and juxtamembrane interactions,
      resulting in receptor activation and cell transformation. Glutamine 17 in the
      transmembrane domain of the 44-amino-acid E5 protein is critical for complex
      formation and receptor activation, and we previously proposed that glutamine 17
      forms a hydrogen bond with threonine 513 of the PDGF beta receptor. We have
      constructed and analyzed mutant E5 proteins containing all possible amino acids
      at position 17 and examined the ability of these proteins to transform C127
      fibroblasts, which express endogenous PDGF beta receptor. Although several
      position 17 mutants were able to transform cells, mutants containing amino acids
      with side groups that were unable to participate in hydrogen bonding interactions
      did not form a stable complex with the PDGF beta receptor or transform cells, in
      agreement with the proposed interaction between position 17 of the E5 protein and
      threonine 513 of the receptor. The nature of the residue at position 17 also
      affected the ability of the E5 proteins to dimerize. Overall, there was an
      excellent correlation between the ability of the various E5 mutant proteins to
      bind the PDGF beta receptor, lead to receptor tyrosine phosphorylation, and
      transform cells. Similar results were obtained in Ba/F3 hematopoietic cells
      expressing exogenous PDGF beta receptor. In addition, treatment of E5-transformed
      cells with a specific inhibitor of the PDGF receptor tyrosine kinase reversed the
      transformed phenotype. These results confirm the central importance of the PDGF
      beta receptor in mediating E5 transformation and highlight the critical role of
      the residue at position 17 of the E5 protein in the productive interaction with
      the PDGF beta receptor. On the basis of molecular modeling analysis and the known
      chemical properties of the amino acids, we suggest a structural basis for the
      role of the residue at position 17 in E5 dimerization and in complex formation
      between the E5 protein and the PDGF beta receptor.

PMID- 9765438
TI  - The herpes simplex virus gE-gI complex facilitates cell-to-cell spread and binds
      to components of cell junctions.
AB  - The herpes simplex virus (HSV) glycoprotein complex gE-gI mediates the spread of
      viruses between adjacent cells, and this property is especially evident for cells
      that form extensive cell junctions, e.g., epithelial cells, fibroblasts, and
      neurons. Mutants lacking gE or gI are not compromised in their ability to enter
      cells as extracellular viruses. Therefore, gE-gI functions specifically in the
      movement of virus across cell-cell contacts and, as such, provides a molecular
      handle on this poorly understood process. We expressed gE-gI in human epithelial
      cells by using replication-defective adenovirus (Ad) vectors. gE-gI accumulated
      at lateral surfaces of the epithelial cells, colocalizing with the adherens
      junction protein beta-catenin but was not found on either the apical or basal
      plasma membranes and did not colocalize with ZO-1, a component of tight
      junctions. In subconfluent monolayers, gE-gI was found at cell junctions but was
      absent from those lateral surfaces not in contact with another cell, as was the
      case for beta-catenin. Similar localization of gE-gI to cell junctions was
      observed in HSV-infected epithelial cells. By contrast, HSV glycoprotein gD,
      expressed using a recombinant Ad vectors, was found primarily along the apical
      surfaces of cells, with little or no protein found on the basal or lateral
      surfaces. Expression of gE-gI without other HSV polypeptides did not cause
      redistribution of either ZO-1 or beta-catenin or alter tight-junction functions.
      Together these results support a model in which gE-gI accumulates at sites of
      cell-cell contact by interacting with junctional components. We hypothesize that
      gE-gI mediates transfer of HSV across cell junctions by virtue of these
      interactions with cell junction components.

PMID- 9765439
TI  - Development of a neutralizing antibody response during acute primary human
      immunodeficiency virus type 1 infection and the emergence of antigenic variants.
AB  - We monitored the primary humoral response to human immunodeficiency virus type 1
      infection and showed that, in addition to antibodies to p24 and gp41, antigens
      which form the basis of most diagnostic assays, the response included a
      significant antibody response directed to the gp120 region of the infecting viral
      quasispecies. When tested in a recombinant virus neutralization assay, these
      antibodies were capable of inhibiting viral growth. We found the primary viral
      quasispecies to solely utilize the CCR-5 chemokine receptor; however, recombinant
      viruses differed in their cytopathology and in their sensitivity to beta
      chemokine inhibition of viral growth. Sequence analysis of the gp120 open reading
      frames showed that amino acid changes in the C1 (D-->G at position 62) and C4 (V-
      >A at position 430) regions accounted for the phenotypic differences. These data
      demonstrate that early in infection, polymorphism exists in envelope glycoprotein
      coreceptor interactions and imply that therapeutic strategies targeted at this
      step in the viral life cycle may lead to rapid resistance.

PMID- 9765440
TI  - Tat protein induces human immunodeficiency virus type 1 (HIV-1) coreceptors and
      promotes infection with both macrophage-tropic and T-lymphotropic HIV-1 strains.
AB  - Chemokine receptors CCR5 and CXCR4 are the primary fusion coreceptors utilized
      for CD4-mediated entry by macrophage (M)- and T-cell line (T)-tropic human
      immunodeficiency virus type 1 (HIV-1) strains, respectively. Here we demonstrate
      that HIV-1 Tat protein, a potent viral transactivator shown to be released as a
      soluble protein by infected cells, differentially induced CXCR4 and CCR5
      expression in peripheral blood mononuclear cells. CCR3, a less frequently used
      coreceptor for certain M-tropic strains, was also induced. CXCR4 was induced on
      both lymphocytes and monocytes/macrophages, whereas CCR5 and CCR3 were induced on
      monocytes/macrophages but not on lymphocytes. The pattern of chemokine receptor
      induction by Tat was distinct from that by phytohemagglutinin. Moreover, Tat
      induced CXCR4 and CCR5 expression was dose dependent. Monocytes/macrophages were
      more susceptible to Tat-mediated induction of CXCR4 and CCR5 than lymphocytes,
      and CCR5 was more readily induced than CXCR4. The concentrations of Tat effective
      in inducing CXCR4 and CCR5 expression were within the picomolar range and close
      to the range of extracellular Tat observed in sera from HIV-1-infected
      individuals. The induction of CCR5 and CXCR4 expression correlated with Tat
      enhanced infectivity of M- and T-tropic viruses, respectively. Taken together,
      our results define a novel role for Tat in HIV-1 pathogenesis that promotes the
      infectivity of both M- and T-tropic HIV-1 strains in primary human leukocytes,
      notably in monocytes/macrophages.

PMID- 9765441
TI  - In vivo footprinting of the enhancer sequences in the upstream long terminal
      repeat of Moloney murine leukemia virus: differential binding of nuclear factors
      in different cell types.
AB  - The enhancer sequences in the Moloney murine leukemia virus (M-MuLV) long
      terminal repeat (LTR) are of considerable interest since they are crucial for
      virus replication and the ability of the virus to induce T lymphomas. While
      extensive studies have identified numerous nuclear factors that can potentially
      bind to M-MuLV enhancer DNA in vitro, it has not been made clear which of these
      factors are bound in vivo. To address this problem, we carried out in vivo
      footprinting of the M-MuLV enhancer in infected cells by in vivo treatment with
      dimethyl sulfate (DMS) followed by visualization through ligation-mediated PCR
      (LMPCR) and gel electrophoresis. In vivo DMS-LMPCR footprinting of the upstream
      LTR revealed evidence for factor binding at several previously characterized
      motifs. In particular, protection of guanines in the central LVb/Ets and Core
      sites within the 75-bp repeats was detected in infected NIH 3T3 fibroblasts, Ti-6
      lymphoid cells, and thymic tumor cells. In contrast, factor binding at the NF-1
      sites was found in infected fibroblasts but not in T-lymphoid cells. These
      results are consistent with the results of previous experiments indicating the
      importance of the LVb/Ets and Core sequences for many retroviruses and the
      biological importance especially of the NF-1 sites in fibroblasts and T-lymphoid
      cells. No evidence for factor binding to the glucocorticoid responsive element
      and LVa sites was found. Additional sites of protein binding included a region in
      the GC-rich sequences downstream of the 75-bp repeats (only in fibroblasts), a
      hypersensitive guanine on the minus strand in the LVc site (only in T-lymphoid
      cells), and a region upstream of the 75-bp repeats. These experiments provide
      concrete evidence for the differential in vivo binding of nuclear factors to the
      M-MuLV enhancers in different cell types.

PMID- 9765442
TI  - Cytotoxic T-lymphocyte precursor frequencies in BALB/c mice after acute
      respiratory syncytial virus (RSV) infection or immunization with a formalin
      inactivated RSV vaccine.
AB  - A better understanding of the immune response to live and formalin-inactivated
      respiratory syncytial virus (RSV) is important for developing nonlive vaccines.
      In this study, major histocompatibility complex (MHC) class I- and II-restricted,
      RSV-specific cytotoxic T-lymphocyte precursor (CTLp) frequencies were determined
      in bronchoalveolar lavage (BAL) samples and spleen lymphocytes of BALB/c mice
      intranasally infected with live RSV or intramuscularly inoculated with formalin
      inactivated RSV (FI-RSV). After RSV infection, both class I- and class II
      restricted CTLps were detected by day 4 or 5 postinfection (p.i.). Peak CTLp
      frequencies were detected by day 7 p.i. The class II-restricted CTLp frequencies
      in the BAL following RSV infection were less than class I-restricted CTLp
      frequencies through day 14 p.i., during which class I-restricted CTLp frequencies
      remained elevated, but then declined by 48 days p.i. The frequencies of class II
      restricted CTLps in the BAL were 2- to 10-fold less than those of class I
      restricted CTLps. For spleen cells, frequencies of both MHC class I- and II
      restricted CTLps to live RSV were similar. In contrast, class II-restricted CTLps
      predominated in FI-RSV-vaccinated mice. RSV challenge of vaccinated mice resulted
      in an increase in the frequency of class I-restricted CTLps at day 3 p.i. but did
      not enhance class II-restricted CTLp frequencies. These studies demonstrate
      differences in the CTLp response to live RSV infection compared with FI-RSV
      immunization and help define possible mechanisms of enhanced disease after FI-RSV
      immunization. In addition, these studies provide a quantitative means to address
      potential vaccine candidates by examining both MHC class I- and II-restricted
      CTLp frequencies.

PMID- 9765444
TI  - African swine fever virus is enveloped by a two-membraned collapsed cisterna
      derived from the endoplasmic reticulum.
AB  - During the cytoplasmic maturation of African swine fever virus (ASFV) within the
      viral factories, the DNA-containing core becomes wrapped by two shells, an inner
      lipid envelope and an outer icosahedral capsid. We have previously shown that the
      inner envelope is derived from precursor membrane-like structures on which the
      capsid layer is progressively assembled. In the present work, we analyzed the
      origin of these viral membranes and the mechanism of envelopment of ASFV.
      Electron microscopy studies on permeabilized infected cells revealed the presence
      of two tightly apposed membranes within the precursor membranous structures as
      well as polyhedral assembling particles. Both membranes could be detached after
      digestion of intracellular virions with proteinase K. Importantly, membrane loop
      structures were observed at the ends of open intermediates, which suggests that
      the inner envelope is derived from a membrane cisterna. Ultraestructural and
      immunocytochemical analyses showed a close association and even direct
      continuities between the endoplasmic reticulum (ER) and assembling virus
      particles at the bordering areas of the viral factories. Such interactions become
      evident with an ASFV recombinant that inducibly expresses the major capsid
      protein p72. In the absence of the inducer, viral morphogenesis was arrested at a
      stage at which partially and fully collapsed ER cisternae enwrapped the core
      material. Together, these results indicate that ASFV, like the poxviruses,
      becomes engulfed by a two-membraned collapsed cisterna derived from the ER.

PMID- 9765443
TI  - Molecular cloning and characterization of viruses isolated from chimpanzees with
      pathogenic human immunodeficiency virus type 1 infections.
AB  - We have previously described the development of AIDS in a chimpanzee (C499)
      infected with human immunodeficiency virus type 1 (HIV-1) and the subsequent
      pathogenic HIV-1 infection in another chimpanzee (C455) transfused with blood
      from C499 (F. J. Novembre et al., J. Virol. 71:4086-4091, 1997). In the present
      study, two virus isolates were derived from these animals: HIV-1JC from
      peripheral blood mononuclear cells (PBMC) of C499, and HIV-1NC from plasma of
      C455. These virus isolates were used to generate two infectious molecular clones,
      termed HIV-1JC16 and HIV-1NC7 (JC16 and NC7, respectively). Comparative analyses
      of the sequences of the two clones showed that they were highly interrelated but
      distinct. Based on heteroduplex mobility assays, JC16 and NC7 appear to represent
      dominant viruses in the uncloned stock population. Compared with amino acid
      sequences of the parental viruses HIV-1SF2, HIV-1LAV-1b, and HIV-1NDK, JC16 and
      NC7 showed a number of differences, including insertions, deletions, and point
      mutations spread throughout the genome. However, insertion/deletion footprints in
      several genes of both JC16 and NC7 suggested that recombination between SF2 and
      LAV-1b could have occurred, possibly contributing to the generation of a
      pathogenic virus. Comparative in vitro analyses of the molecular clones and the
      uncloned stocks of HIV-1JC and HIV-1NC revealed that these viruses had strikingly
      similar replicative abilities in mitogen-stimulated PBMC and in macrophages.
      Compared to the SF2 and LAV-1b isolates of HIV-1, HIV-1JC and HIV-1NC isolates
      were more similar to LAV-1b with respect to the ability to replicate in mitogen
      stimulated PBMC and macrophages. These viruses should prove to be useful in
      mapping determinants of pathogenesis.

PMID- 9765446
TI  - Functional differences between BHRF1, the Epstein-Barr virus-encoded Bcl-2
      homologue, and Bcl-2 in human epithelial cells.
AB  - BHRF1, a component of the restricted early antigen complex of the Epstein-Barr
      virus lytic cycle, encodes a 17-kDa protein with both sequence and functional
      homology to the antiapoptotic Bcl-2 oncogene. Recent work has suggested that
      BHRF1 behaves like Bcl-2 in protecting cells from apoptosis induced by a range of
      stimuli. In this study, the effect of BHRF1 and Bcl-2 on the growth and
      differentiation of the SCC12F human epithelial cell line was examined. The levels
      of stable transfected BHRF1 expression achievable in SCC12F cells was
      consistently lower than that obtained with Bcl-2. While both BHRF1 and Bcl-2
      inhibited epithelial differentiation, the effect of Bcl-2 was more pronounced,
      resulting in an almost complete blockade of differentiation in organotypic raft
      cultures. However, BHRF1-expressing SCC12F cells proliferated at a much higher
      rate than SCC12F cells expressing Bcl-2, and this effect was supported by cell
      cycle analysis which demonstrated that BHRF1, but not Bcl-2, promotes rapid
      transit through the cell cycle. These data highlight important differences
      between BHRF1 and Bcl-2 and suggest that BHRF1 may function to promote the
      survival and proliferation of lytically infected cells. The proliferative
      properties of BHRF1 described in this study, together with the demonstration that
      other oncogenic gamma herpesviruses encode Bcl-2 homologues, suggests that these
      proteins may serve to increase the susceptibility of virus-infected cells to
      oncogenic transformation, thereby contributing to the development of virus
      associated tumors.

PMID- 9765445
TI  - Analysis of pol gene heterogeneity, viral quasispecies, and drug resistance in
      individuals infected with group O strains of human immunodeficiency virus type 1.
AB  - Nucleotide sequences of the reverse transcriptase (RT) coding region have been
      compared in four new human immunodeficiency virus type 1 (HIV-1) group O
      isolates. Phylogenetic analysis of this pol region highlights a cluster of these
      four HIV-1 group O sequences with seven other group O isolates (5% intracluster
      nucleotide sequence diversity) similar to clusters classified as subtypes in HIV
      1 group M (an average of 4.9% intrasubtype sequence diversity). Based on these
      analyses, this group O cluster has been designated subtype A-O. A longitudinal
      study of a heterosexual couple infected with group O (ESP1 and ESP2) allowed a
      detailed analysis of RT sequences (amino acids 28 to 219). Directed evolution and
      a slightly higher mutation frequency was observed in the RT sequences of patient
      ESP2, treated with antiretroviral drugs, than that from the untreated patient
      ESP1. Antiretroviral treatment also selected for specific substitutions, M184V
      and T215Y in the RT coding region, conferring resistance to 3'-dideoxy-3'
      thiacytidine and zidovudine, respectively. A Gly98 to Glu RT substitution
      identified in the treated patient suggests a possible reversion of a
      nonnucleoside RT inhibitor-resistant phenotype. Using RT clones from this
      longitudinal study, both heteroduplex tracking assay and cloning-sequencing
      techniques were employed for an extensive genetic analysis of pol gene
      quasispecies. Amino acid substitutions (i.e., Phe-77 to Leu, Lys-101 to Glu, and
      Val-106 to Iso) associated with antiretroviral resistance were identified in RT
      clones from HIV-1 group O-infected patients not subjected to drug therapy or
      treated with unrelated drugs. Finally, phylogenetic relationships between RT
      clones of the treated ESP2 patient and those of the untreated ESP1 patient show
      how drug pressure can direct evolution of viral pol gene quasispecies
      independently of direct drug-resistant substitutions.

PMID- 9765447
TI  - The role of in vitro-induced lymphocyte apoptosis in feline immunodeficiency
      virus infection: correlation with different markers of disease progression.
AB  - Human immunodeficiency virus infection is characterized by a progressive decline
      in the number of peripheral blood CD4(+) T lymphocytes, which finally leads to
      AIDS. This T-cell decline correlates with the degree of in vitro-induced
      lymphocyte apoptosis. However, such a correlation has not yet been described in
      feline AIDS, caused by feline immunodeficiency virus (FIV) infection. We
      therefore investigated the intensity of in vitro-induced apoptosis in peripheral
      blood lymphocytes from cats experimentally infected with a Swiss isolate of FIV
      for 1 year and for 6 years and from a number of long-term FIV-infected cats which
      were coinfected with feline leukemia virus. Purified peripheral blood lymphocytes
      were either cultured overnight under nonstimulating conditions or stimulated with
      phytohemagglutinin and interleukin-2 for 60 h. Under stimulating conditions, the
      isolates from the infected cats showed significantly higher relative counts of
      apoptotic cells than did those from noninfected controls (1-year-infected cats, P
      = 0.01; 6-year-infected cats, P = 0.006). The frequency of in vitro-induced
      apoptosis was inversely correlated with the CD4(+) cell count (P = 0. 002),
      bright CD8(+) cell count (P = 0.009), and CD4/CD8 ratio (P = 0. 01) and directly
      correlated with the percentage of bright major histocompatibility complex class
      II-positive peripheral blood lymphocytes (P = 0.004). However, we found no
      correlation between in vitro-induced apoptosis and the viral load in serum
      samples. Coinfection with feline leukemia virus enhanced the degree of in vitro
      induced apoptosis compared with that in FIV monoinfected cats. We concluded that
      the degree of in vitro-induced apoptosis was closely related to FIV-mediated T
      cell depletion and lymphocyte activation and could be used as an additional
      marker for disease progression in FIV infection.

PMID- 9765448
TI  - Importance of basic residues in the nucleocapsid sequence for retrovirus Gag
      assembly and complementation rescue.
AB  - The Gag proteins of Rous sarcoma virus (RSV) and human immunodeficiency virus
      (HIV) contain small interaction (I) domains within their nucleocapsid (NC)
      sequences. These overlap the zinc finger motifs and function to provide the
      proper density to viral particles. There are two zinc fingers and at least two I
      domains within these Gag proteins. To more thoroughly characterize the important
      sequence features and properties of I domains, we analyzed Gag proteins that
      contain one or no zinc finger motifs. Chimeric proteins containing the amino
      terminal half of RSV Gag and various portions of the carboxy terminus of murine
      leukemia virus (MLV) (containing one zinc finger) Gag had only one I domain,
      whereas similar chimeras with human foamy virus (HFV) (containing no zinc
      fingers) Gag had at least two. Mutational analysis of the MLV NC sequence and
      inspection of I domain sequences within the zinc-fingerless C terminus of HFV Gag
      suggested that clusters of basic residues, but not the zinc finger motif residues
      themselves, are required for the formation of particles of proper density. In
      support of this, a simple string of strongly basic residues was found to be able
      to substitute for the RSV I domains. We also explored the possibility that
      differences in I domains (e.g., their number) account for differences in the
      ability of Gag proteins to be rescued into particles when they are unable to bind
      to membranes. Previously published experiments have shown that such membrane
      binding mutants of RSV and HIV (two I domains) can be rescued but that those of
      MLV (one I domain) cannot. Complementation rescue experiments with RSV-MLV
      chimeras now map this difference to the NC sequence of MLV. Importantly, the same
      RSV-MLV chimeras could be rescued by complementation when the block to budding
      was after, rather than before, transport to the membrane. These results suggest
      that MLV Gag molecules begin to interact at a much later time after synthesis
      than those of RSV and HIV.

PMID- 9765449
TI  - Neuronal death induced by brain-derived human immunodeficiency virus type 1
      envelope genes differs between demented and nondemented AIDS patients.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection of the brain results in
      viral replication primarily in macrophages and microglia. Despite frequent
      detection of viral genome and proteins in the brains of AIDS patients with and
      without HIV dementia, only 20% of AIDS patients become demented. To investigate
      the role of viral envelope gene variation in the occurrence of dementia, we
      examined regions of variability in the viral envelope gene isolated from brains
      of AIDS patients. Brain-derived HIV-1 V1-V2 envelope sequences from seven
      demented and six nondemented AIDS patients displayed significant sequence
      differences between clinical groups, and by phylogenetic analysis, sequences from
      the demented group showed clustering. Infectious recombinant viruses containing
      brain-derived V3 sequences from both clinical groups were macrophagetropic, and
      viruses containing brain-derived V1, V2, and V3 sequences from both clinical
      groups spread efficiently in macrophages. In an indirect in vitro neurotoxicity
      assay using supernatant fluid from HIV-1-infected macrophages, recombinant
      viruses from demented patients induced greater neuronal death than viruses from
      nondemented patients. Thus, the HIV-1 envelope diversity observed in these
      patient groups appeared to influence the release of neurotoxic molecules from
      macrophages and might account in part for the variability in occurrence of
      dementia in AIDS patients.

PMID- 9765451
TI  - A bipartite membrane-binding signal in the human immunodeficiency virus type 1
      matrix protein is required for the proteolytic processing of Gag precursors in a
      cell type-dependent manner.
AB  - It is unclear whether proteolytic processing of the human immunodeficiency virus
      type 1 (HIV-1) Gag protein is dependent on virus assembly at the plasma membrane.
      Mutations that prevent myristylation of HIV-1 Gag proteins have been shown to
      block virus assembly and release from the plasma membrane of COS cells but do not
      prevent processing of Gag proteins. In contrast, in HeLa cells similar mutations
      abolished processing of Gag proteins as well as virus production. We have now
      addressed this issue with CD4(+) T cells, which are natural target cells of HIV
      1. In these cells, myristylation of Gag proteins was required for proteolytic
      processing of Gag proteins and production of extracellular viral particles. This
      result was not due to a lack of expression of the viral protease in the form of a
      Gag-Pol precursor or a lack of interaction between unmyristylated Gag and Gag-Pol
      precursors. The processing defect of unmyristylated Gag was partially rescued ex
      vivo by coexpression with wild-type myristylated Gag proteins in HeLa cells. The
      cell type-dependent processing of HIV-1 Gag precursors was also observed when
      another part of the plasma membrane binding signal, a polybasic region in the
      matrix protein, was mutated. The processing of unmyristylated Gag precursors was
      inhibited in COS cells by HIV-1 protease inhibitors. Altogether, our findings
      demonstrate that the processing of HIV-1 Gag precursors in CD4(+) T cells occurs
      normally at the plasma membrane during viral morphogenesis. The intracellular
      environment of COS cells presumably allows activation of the viral protease and
      proteolytic processing of HIV-1 Gag proteins in the absence of plasma membrane
      binding.

PMID- 9765450
TI  - Costimulation of naive CD8(+) lymphocytes induces CD4 expression and allows human
      immunodeficiency virus type 1 infection.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection requires cell surface
      expression of CD4. Costimulation of CD8(+)/CD4(-) T lymphocytes by anti-CD3 and
      anti-CD28 antibodies or by allogeneic dendritic cells induced expression of CD4
      and rendered these CD8 cells susceptible to HIV-1 infection. Naive CD45RA+ cells
      responded with greater expression of CD4 than did CD45RO+ cells. CD8(+)
      lymphocytes derived from fetal or newborn sources exhibited a greater tendency to
      express CD4, consistent with their naive states. This mechanism of infection
      suggests HIV-induced perturbation of the CD8 arm of the immune response and could
      explain the generally rapid disease progression seen in HIV-infected children.

PMID- 9765452
TI  - Oral immunization of macaques with attenuated vaccine virus induces protection
      against vaginally transmitted AIDS.
AB  - The chimeric simian-human immunodeficiency virus SHIVKU-1, bearing the envelope
      of human immunodeficiency virus type 1 (HIV-1), causes fulminant infection with
      subtotal loss of CD4(+) T cells followed by development of AIDS in intravaginally
      inoculated macaques and thus provides a highly relevant model of sexually
      transmitted disease caused by HIV-1 in human beings. Previous studies using this
      SHIV model had shown that the vpu and nef genes were important in pathogenesis of
      the infection, and so we deleted portions of these genes to create two vaccines,
      DeltavpuDeltanefSHIV-4 (vaccine 1) and DeltavpuSHIVPPc (vaccine 2). Six adult
      macaques were immunized subcutaneously with vaccine 1, and six were immunized
      orally with vaccine 2. Both viruses caused infection in all inoculated animals,
      but whereas vaccine 1 virus caused only a nonproductive type of infection,
      vaccine 2 virus replicated productively but transiently for a 6- to 10-week
      period. Both groups were challenged 6 to 7 months later with pathogenic SHIVKU-1
      by the intravaginal route. All four unvaccinated controls developed low CD4(+) T
      cell counts (<200/microliter) and AIDS. The 12 vaccinated animals all became
      infected with SHIVKU-1, and two in group 1 developed a persistent productive
      infection followed by development of AIDS in one. The other 10 have maintained
      almost complete control over virus replication even though spliced viral RNA was
      detected in lymph nodes. This suppression of virus replication correlated with
      robust antiviral cell-mediated immune responses. This is the first demonstration
      of protection against virulent SHIV administered by the intravaginal route. This
      study supports the concept that sexually transmitted HIV disease can be prevented
      by parenteral or oral immunization.

PMID- 9765453
TI  - Structure and function of a ganglioside receptor for porcine rotavirus.
AB  - A ganglioside fraction isolated from pooled intestines from newborn to 4-week-old
      piglets, which we previously partially characterized and showed to specifically
      inhibit the binding of porcine rotavirus (OSU strain) to host cells (M. D.
      Rolsma, H. B. Gelberg, and M. S. Kuhlenschmidt, J. Virol. 68:258-268, 1994), was
      further purified and found to contain two major monosialogangliosides. Each
      ganglioside was purified to apparent homogeneity, and their carbohydrate
      structure was examined by high-pH anion-exchange chromatography coupled with
      pulsed amperometric detection and fast atom bombardment mass spectroscopy. Both
      gangliosides possessed a sialyllactose oligosaccharide moiety characteristic of
      GM3 gangliosides. Compositional analyses indicated that each ganglioside was
      composed of sialic acid, galactose, glucose, and sphingosine in approximately a
      1:1:1:1 molar ratio. Each ganglioside differed, however, in the type of sialic
      acid residue it contained. An N-glycolylneuraminic acid (NeuGc) moiety was found
      in the more polar porcine GM3, whereas the less polar GM3 species contained N
      acetylneuraminic acid (NeuAc). Both NeuGcGM3 and NeuAcGM3 displayed dose
      dependent inhibition of virus binding to host cells. NeuGcGM3 was approximately
      two to three times more effective than NeuAcGM3 in blocking virus binding.
      Inhibition of binding occurred with as little as 400 pmol of NeuGcGM3/50 ng of
      virus (approximately 2 x 10(7) virions) and 2 x 10(6) cells/ml. Fifty percent
      inhibition of binding was achieved with 0.64 and 1.5 microM NeuGcGM3 and
      NeuAcGM3, respectively. The free oligosaccharides 3'- and 6'-sialyllactose
      inhibited binding 50% at millimolar concentrations, which were nearly 1,000 times
      the concentration of intact gangliosides required for the same degree of
      inhibition. Direct binding of infectious, triple-layer rotavirus particles, but
      not noninfectious, double-layered rotavirus particles, to NeuGcGM3 and NeuAcGM3
      was demonstrated by using a thin-layer chromatographic overlay assay. NeuGcGM3
      and NeuAcGM3 inhibited virus infectivity of MA-104 cells by 50% at concentrations
      of 3.97 and 9. 84 microM, respectively. NeuGcGM3 (700 nmol/g [dry weight] of
      intestine) was found to be the predominant enterocyte ganglioside (comprising 75%
      of the total lipid-bound sialic acid) in neonatal piglets, followed by NeuAcGM3
      (200 nmol/g [dry weight] of intestine). NeuGcGM3 and NeuAcGM3 together comprised
      nearly 100% of the lipid-bound sialic acid in the neonatal intestine, but their
      quantities rapidly diminished during the first 5 weeks of life. These data
      support the hypothesis that porcine NeuGcGM3 and NeuAcGM3 are physiologically
      relevant receptors for porcine rotavirus (OSU strain). Further support for this
      hypothesis was obtained from virus binding studies using mutant or neuraminidase
      treated cell lines. Lec-2 cells, a mutant clone of CHO cells characterized by a
      90% reduction in sialyllation of its glycoconjugates, bound less than 5% of the
      virus compared to control cell binding. In contrast, Lec-1 cells, a mutant CHO
      clone characterized by a deficiency in glycosylation of N-linked
      oligosaccharides, still bound rotavirus. Furthermore, exogenous addition of
      NeuGcGM3 to the Lec-2 mutant cells restored their ability to bind rotavirus in
      amounts equivalent to that of their parent (CHO) cell line. In the virus
      permissive MA-104 cell line, NeuGcGM3 was also able to partially restore
      rotavirus infectivity in neuraminidase-treated cells. These data suggest that
      gangliosides play a major role in recognition of host cells by porcine rotavirus
      (OSU strain).

PMID- 9765454
TI  - Studies of the neutralizing activity and avidity of anti-human immunodeficiency
      virus type 1 Env antibody elicited by DNA priming and protein boosting.
AB  - DNA vaccination is an effective means of eliciting strong antibody responses to a
      number of viral antigens. However, DNA immunization alone has not generated
      persistent, high-titer antibody and neutralizing antibody responses to human
      immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env). We have
      previously reported that DNA-primed anti-Env antibody responses can be augmented
      by boosting with Env-expressing recombinant vaccinia viruses. We report here that
      recombinant Env protein provides a more effective boost of DNA-initiated antibody
      responses. In rabbits primed with Env-expressing plasmids, protein boosting
      increased titer, persistence, neutralizing activity, and avidity of anti-Env
      responses. While titers increased rapidly after boosting, avidity and
      neutralizing activity matured more slowly over a 6-month period following protein
      boosting. DNA priming and protein immunization with HIV-1 HXB-2 Env elicited
      neutralizing antibody for T cell line-adapted, but not primary isolate, viruses.
      The most effective neutralizing antibody responses were observed after priming
      with plasmids which expressed noninfectious virus-like particles. In contrast to
      immunizations with HIV-1 Env, DNA immunizations with the influenza virus
      hemagglutinin glycoprotein did not require a protein boost to achieve high-titer
      antibody with good avidity and persistence.

PMID- 9765455
TI  - Role of variable regions A and B in receptor binding domain of amphotropic murine
      leukemia virus envelope protein.
AB  - For the amphotropic murine leukemia virus (MuLV), a 208-amino-acid amino-terminal
      fragment of the surface unit (SU) of the envelope glycoprotein is sufficient to
      bind to its receptor, Pit2. Within this binding domain, two hypervariable
      regions, VRA and VRB, have been proposed to be important for receptor
      recognition. In order to specifically locate residues that are important for the
      interaction with Pit2, we generated a number of site-specific mutations in both
      VRA and VRB and analyzed the resulting envelope proteins when expressed on
      retroviral vectors. Concurrently, we substituted portions of the amphotropic SU
      with homologous regions from the polytropic MuLV envelope protein. The
      amphotropic SU was unaffected by most of the point mutations we introduced. In
      addition, the deletion of eight residues in a region of VRA that was previously
      suggested to be essential for Pit2 utilization only decreased titer on NIH 3T3
      cells by 1 order of magnitude. Although the replacement of the amino-terminal two
      thirds of VRA with the polytropic sequence abolished receptor binding, smaller
      nonoverlapping substitutions did not affect the function of the protein. We were
      not able to identify a single critical receptor contact point within VRA, and we
      suggest that the amphotropic receptor binding domain probably makes multiple
      contacts with the receptor and that the loss of some of these contacts can be
      tolerated.

PMID- 9765456
TI  - Neurovirulence in feline immunodeficiency virus-infected neonatal cats is viral
      strain specific and dependent on systemic immune suppression.
AB  - Feline immunodeficiency virus (FIV) is a lentivirus that causes immune
      suppression and neurological disease in cats. Among animal viruses, individual
      viral strains have been shown to be neurovirulent, but the role of viral strain
      specificity among lentiviruses and its relationship to systemic immune
      suppression in the development of neurological disease remains uncertain. To
      determine the extent to which different FIV strains caused neurological disease,
      FIV V1CSF and Petaluma were compared in ex vivo assays and in vivo. Both viruses
      infected and replicated in macrophage and mixed glial cell cultures at similar
      levels, but V1CSF induced significantly greater neuronal death than Petaluma in a
      neurotoxicity assay. V1CSF-infected animals showed significant neurodevelopmental
      delay compared to the Petaluma-infected and uninfected animals. Magnetic
      resonance spectroscopy studies of frontal cortex revealed significantly reduced N
      acetyl aspartate/creatine ratios in the V1CSF group compared to the other groups.
      Cyclosporin A treatment of Petaluma-infected animals caused neurodevelopmental
      delay and reduced N-acetyl aspartate/creatine ratios in the brain. Reduced CD4(+)
      and CD8(+) cell counts were observed in the V1CSF-infected group compared to the
      uninfected and Petaluma-infected groups. These findings suggest that
      neurodevelopmental delay and neuronal injury is FIV strain specific but that
      systemic immune suppression is also an important determinant of FIV-induced
      neurovirulence.

PMID- 9765457
TI  - Duck hepatitis B virus nucleocapsids formed by N-terminally extended or C
      terminally truncated core proteins disintegrate during viral DNA maturation.
AB  - Hepadnaviruses are DNA viruses that replicate through reverse transcription of an
      RNA pregenome. Viral DNA synthesis takes place inside viral nucleocapsids, formed
      by core protein dimers. Previous studies have identified carboxy-terminal
      truncations of the core protein that affect viral DNA maturation. Here, we
      describe the effect of small amino-terminal insertions into the duck hepatitis B
      virus (DHBV) core protein on viral DNA replication. All insertion mutants formed
      replication-competent nucleocapsids. Elongation of viral DNA, however, appeared
      to be incomplete. Increasing the number of additional amino acids and introducing
      negatively charged residues further reduced the observed size of mature viral DNA
      species. Mutant core proteins did not inhibit the viral polymerase. Instead,
      viral DNA synthesis destabilized mutant nucleocapsids, rendering mature viral DNA
      selectively sensitive to nuclease action. Interestingly, the phenotype of two
      previously described carboxy-terminal DHBV core protein deletion mutants was
      found to be based on the same mechanism. These data suggest that (i) the amino-
      as well as the carboxy-terminal portion of the DHBV core protein plays a critical
      role in nucleocapsid stabilization, and (ii) the hepadnavirus polymerase can
      perform partial second-strand DNA synthesis in the absence of intact viral
      nucleocapsids.

PMID- 9765458
TI  - Receptor binding sites and antigenic epitopes on the fiber knob of human
      adenovirus serotype 3.
AB  - The adenovirus fiber knob causes the first step in the interaction of adenovirus
      with cell membrane receptors. To obtain information on the receptor binding
      site(s), the interaction of labeled cell membrane proteins to synthetic peptides
      covering the adenovirus type 3 (Ad3) fiber knob was studied. Peptide P6 (amino
      acids [aa] 187 to 200), to a lesser extent P14 (aa 281 to 294), and probably P11
      (aa 244 to 256) interacted specifically with cell membrane proteins, indicating
      that these peptides present cell receptor binding sites. Peptides P6, P11, and
      P14 span the D, G, and I beta-strands of the R-sheet, respectively. The other
      reactive peptides, P2 (aa 142 to 156), P3 (aa 153 to 167), and P16 (aa 300 to
      319), probably do not present real receptor binding sites. The binding to these
      six peptides was inhibited by Ad3 virion and was independent of divalent cations.
      We have also screened the antigenic epitopes on the knob with recombinant Ad3
      fiber, recombinant Ad3 fiber knob, and Ad3 virion-specific antisera by enzyme
      linked immunosorbent assay. The main antigenic epitopes were presented by P3, P6,
      P12 (aa 254 to 269), P14, and especially the C-terminal P16. Peptides P14 and P16
      of the Ad3 fiber knob were able to inhibit Ad3 infection of cells.

PMID- 9765459
TI  - The PK domain of the large subunit of herpes simplex virus type 2 ribonucleotide
      reductase (ICP10) is required for immediate-early gene expression and virus
      growth.
AB  - The large subunit of herpes simplex virus (HSV) ribonucleotide reductase (RR),
      RR1, contains a unique amino-terminal domain which has serine/threonine protein
      kinase (PK) activity. To examine the role of the PK activity in virus
      replication, we studied an HSV type 2 (HSV-2) mutant with a deletion in the RR1
      PK domain (ICP10DeltaPK). ICP10DeltaPK expressed a 95-kDa RR1 protein (p95) which
      was PK negative but retained the ability to complex with the small RR subunit,
      RR2. Its RR activity was similar to that of HSV-2. In dividing cells, onset of
      virus growth was delayed, with replication initiating at 10 to 15 h
      postinfection, depending on the multiplicity of infection. In addition to the
      delayed growth onset, virus replication was significantly impaired (1,000-fold
      lower titers) in nondividing cells, and plaque-forming ability was severely
      compromised. The RR1 protein expressed by a revertant virus [HSV-2(R)] was
      structurally and functionally similar to the wild-type protein, and the virus had
      wild-type growth and plaque-forming properties. The growth of the ICP10DeltaPK
      virus and its plaque-forming potential were restored to wild-type levels in cells
      that constitutively express ICP10. Immediate-early (IE) genes for ICP4, ICP27,
      and ICP22 were not expressed in Vero cells infected with ICP10DeltaPK early in
      infection or in the presence of cycloheximide, and the levels of ICP0 and p95
      were significantly (three- to sevenfold) lower than those in HSV-2- or HSV-2(R)
      infected cells. IE gene expression was similar to that of the wild-type virus in
      cells that constitutively express ICP10. The data indicate that ICP10 PK is
      required for early expression of the viral regulatory IE genes and, consequently,
      for timely initiation of the protein cascade and HSV-2 growth in cultured cells.

PMID- 9765461
TI  - Epstein-Barr virus contributes to the malignant phenotype and to apoptosis
      resistance in Burkitt's lymphoma cell line Akata.
AB  - In the present study, we established an in vitro system representing the
      Burkitt's lymphoma (BL)-type Epstein-Barr virus (EBV) infection which is
      characterized by expression of EBV-determined nuclear antigen 1 (EBNA-1) and
      absence of EBNA-2 and latent membrane protein 1 (LMP1) expression. EBV-negative
      cell clones isolated from the EBV-positive BL line Akata were infected with an
      EBV recombinant carrying a selectable marker, and the following selection culture
      easily yielded EBV-infected clones. EBV-reinfected clones showed BL-type EBV
      expression and restored the capacity for growth on soft agar and tumorigenicity
      in SCID mice that were originally retained in parental EBV-positive Akata cells
      and lost in EBV-negative subclones. Moreover, it was found that EBV-positive
      cells were more resistant to apoptosis than were EBV-negative cells. EBV-infected
      cells expressed the bcl-2 protein, through which cells might become resistant to
      apoptosis, at a higher level than did uninfected cells. This is the first report
      that BL-type EBV infection confers apoptosis resistance even in the absence of
      expression of LMP1 and BHRF1, both of which are known to have an antiapoptotic
      function. Surprisingly, transfection of the EBNA-1 gene into EBV-negative Akata
      clones could not restore malignant phenotypes and apoptosis resistance, thus
      suggesting that EBNA-1 alone was not sufficient for conferring them. Our results
      suggest that the persistence of EBV in BL cells is required for the cells to be
      more malignant and apoptosis resistant, which underlines the oncogenic role of
      EBV in BL genesis.

PMID- 9765460
TI  - Characterization of a baculovirus-encoded ATP-dependent DNA ligase.
AB  - Sequence analysis of the Lymantria dispar multicapsid nucleopolyhedrovirus
      (LdMNPV) genome identified an open reading frame (ORF) encoding a 548-amino-acid
      (62-kDa) protein that showed 35% amino acid sequence identity with vaccinia virus
      ATP-dependent DNA ligase. Ligase homologs have not been reported from other
      baculoviruses. The ligase ORF was cloned and expressed as an N-terminal histidine
      tagged fusion protein. Incubation of the purified protein with [alpha-32P]ATP
      resulted in formation of a covalent enzyme-adenylate intermediate which ran as a
      62-kDa labeled band on a sodium dodecyl sulfate-polyacrylamide gel. Loss of the
      radiolabeled band occurred upon incubation of the intermediate with
      pyrophosphate, poly(dA) . poly(dT)12-18, or poly(rA) . poly(dT)12-18,
      characteristics of a DNA ligase II or III. The protein was able to ligate a
      double-stranded synthetic DNA substrate containing a single nick and
      inefficiently ligated a 1-nucleotide (nt) gap but did not ligate a 2-nt gap. It
      was able to ligate short, complementary overhangs but not blunt-ended double
      stranded DNA. In a transient DNA replication assay employing six plasmids
      containing the LdMNPV homologs of the essential baculovirus replication genes, a
      plasmid containing the DNA ligase gene was neither essential nor stimulatory. All
      of these results are consistent with the activity of type III DNA ligases, which
      have been implicated in DNA repair and recombination.

PMID- 9765462
TI  - Persistent baculovirus infection results from deletion of the apoptotic
      suppressor gene p35.
AB  - Infection with the wild-type baculovirus Autographa californica multiple nuclear
      polyhedrosis virus (AcMNPV) results in complete death of Spodoptera frugiperda
      (Sf) cells. However, infection of Sf cells with AcMNPV carrying a mutation or
      deletion of the apoptotic suppressor gene p35 allowed the cloning of surviving Sf
      cells that harbored persistent viral genomes. Persistent infection established
      with the virus with p35 mutated or deleted was blocked by stable transfection of
      p35 in the host genome or by insertion of the inhibitor of apoptosis (iap) gene
      into the viral genome. These artificially established persistently virus-infected
      cells became resistant to subsequent viral challenge, and some of the cell lines
      carried large quantities of viral DNA capable of early gene expression.
      Continuous release of viral progenies was evident in some of the persistently
      virus-infected cells, and transfection of p35 further stimulated viral activation
      of the persistent cells, including the reactivation of viruses in those cell
      lines without original continuous virus release. These results have demonstrated
      the successful establishment of persistent baculovirus infections under
      laboratory conditions and that their establishment may provide a novel
      continuous, nonlytic baculovirus expression system in the future.

PMID- 9765463
TI  - Persistence of herpes simplex virus type 1 DNA in chronic conjunctival and eyelid
      lesions of mice.
AB  - Herpes simplex virus type 1 (HSV-1) causes chronic blepharitis and conjunctivitis
      as well as keratitis in humans. The pathogenesis of these inflammatory ocular and
      dermal lesions is not well understood. We have examined the persistence of HSV-1
      DNA and its relationship to inflammatory lesions in the conjunctiva and eyelid
      skin of mice which were inoculated with HSV-1 by the corneal route. Viral DNA was
      detected by in situ PCR in the conjunctiva and eyelid tissue of infected mice at
      5, 11, 23, and 37 days postinfection (p.i.). This DNA was localized in the
      epithelial cells of the conjunctiva and hair follicles and in the epidermal cells
      of the eyelid skin. Viral proteins were not detected in the conjunctiva or the
      eyelid skin after 5 days p.i., even though histopathological lesions were found
      at 23 and 37 days p.i. in both tissues. The DNA-containing cells were adjacent to
      sites of inflammation in the chronic lesions in both the conjunctiva and the
      eyelid skin. A similar temporal and spatial relationship between HSV-1 DNA and
      inflammatory lesions has been previously reported for the cornea. Our data
      suggest that the lesions in the cornea, conjunctiva, and eyelid skin progress
      similarly. Further studies are required to determine whether the long-term
      presence of HSV-1 is involved in the mechanism by which these chronic
      inflammatory lesions develop. The presence of HSV-1 DNA in these extraocular
      tissues for extended periods may constitute persistent viral infection of
      nonneuronal cells.

PMID- 9765464
TI  - Extracellular signal-regulated kinase activity is sustained early during human
      cytomegalovirus infection.
AB  - Expression of many early viral genes during human cytomegalovirus (HCMV)
      infection is dependent on cellular transcription factors. Several immediate-early
      and early viral promoters contain DNA binding sites for cellular factors such as
      CREB, AP-1, serum response factor, and Elk-1, and these transcription factors can
      be activated by phosphorylation via the cellular mitogen-activated protein kinase
      (MAPK) signal transduction cascade. To determine if the extracellular signal
      regulated MAPKs, ERK1 and ERK2, play a role in transcription factor activation
      during infection, we tested for ERK activity during viral infection. We found
      that HCMV infection resulted in the maintenance of previously activated ERK1 and
      ERK2 by a mechanism which appears to involve the inhibition of a cellular
      phosphatase activity. ERK phosphorylation and activity were sustained for at
      least 8 h after infection, whereas in mock-infected cells, ERK activity steadily
      declined by 1 h postinfection. The activity of at least one cellular substrate of
      the ERKs, the protein kinase RSK1, was also maintained during this period. UV
      inactivation experiments suggested that viral gene expression was required for
      sustained ERK activity. In turn, activation of the ERKs appeared to be important
      for viral gene expression, as evidenced by the observed decrease in the
      transcriptional activity of the HCMV UL112-113 promoter during infection in the
      presence of the MEK inhibitor PD98059. These data suggest that HCMV utilizes
      cellular signal transduction pathways to activate viral or cellular transcription
      factors involved in the control of early viral gene expression and DNA
      replication.

PMID- 9765465
TI  - Pseudorabies virus-induced leukocyte trafficking into the rat central nervous
      system.
AB  - When the swine alphaherpesvirus pseudorabies virus (PRV) infects the rat retina,
      it replicates in retinal ganglion cells and invades the central nervous system
      (CNS) via anterograde transynaptic spread through axons in the optic nerve. Virus
      can also spread to the CNS via retrograde transport through the oculomotor
      nucleus that innervates extraocular muscles of the eye. Since retrograde
      infection of the CNS precedes anterograde transynaptic infection, the temporal
      sequence of infection of the CNS depends on the route of invasion. Thus, motor
      neurons are infected first (retrograde infection), followed by CNS neurons
      innervated by the optic nerve (anterograde transynaptic infection). This temporal
      separation in the appearance of virus in separate groups of neurons enabled us to
      compare the immune responses to different stages of CNS infection in the same
      animal. The data revealed focal trafficking of peripheral immune cells into areas
      of the CNS infected by retrograde or anterograde transport after PRV Becker was
      injected into the vitreous body of the eye. Cells expressing the leukocyte common
      antigen, CD45(+), entered the area of infection from local capillaries prior to
      any overt expression of neuropathology, and quantitative analysis demonstrated
      that the number of cells increased in proportion to the number of infected
      neurons within a given region. Recruitment of cells of monocyte/macrophage
      lineage began prior to the appearance of CD8(+) cytotoxic lymphocytes, which
      were, in turn, followed by CD4(+) lymphocytes. These data demonstrate that PRV
      replication in CNS neurons stimulates the focal infiltration of specific classes
      of CD45(+) cells in a time-dependent, temporally organized fashion that is
      correlated directly with the number of infected neurons and the time that a given
      region has been infected.

PMID- 9765466
TI  - Mutations in the N terminus of the brome mosaic virus polymerase affect genetic
      RNA-RNA recombination.
AB  - Previously, we have observed that mutations in proteins 1a and 2a, the two
      virally encoded components of the brome mosaic virus (BMV) replicase, can affect
      the frequency of recombination and the locations of RNA recombination sites (P.
      D. Nagy, A. Dzianott, P. Ahlquist, and J. J. Bujarski, J. Virol. 69:2547-2556,
      1995; M. Figlerowicz, P. D. Nagy, and J. J. Bujarski, Proc. Natl. Acad. Sci. USA
      94:2073-2078, 1997). Also, it was found before that the N-terminal domain of 2a,
      the putative RNA polymerase protein, participates in the interactions between 1a
      and 2a (C. C. Kao, R. Quadt, R. P. Hershberger, and P. Ahlquist, J. Virol.
      66:6322-6329, 1992; E. O'Reilly, J. Paul, and C. C. Kao, J. Virol. 71:7526-7532,
      1997). In this work, we examine how mutations within the N terminus of 2a
      influence RNA recombination in BMV. Because of the likely electrostatic character
      of 1a-2a interactions, five 2a mutants, MF1 to MF5, were generated by replacing
      clusters of acidic amino acids with their neutral counterparts. MF2 and MF5
      retained nearly wild-type levels of 1a-2a interaction and were infectious in
      Chenopodium quinoa. However, compared to that in wild-type virus, the frequency
      of nonhomologous recombination in both MF2 and MF5 was markedly decreased. Only
      in MF2 was the frequency of homologous recombination reduced and the occurrence
      of imprecise homologous recombination increased. In MF5 there was also a 3' shift
      in the positions of homologous crossovers. The observed effects of MF2 and MF5
      reveal that the 2a N-terminal domain participates in different ways in homologous
      and in nonhomologous BMV RNA recombination. This work maps specific locations
      within the N terminus involved in 1a-2a interaction and in recombination and
      further suggests that the mechanisms of the two types of crossovers in BMV are
      different.

PMID- 9765467
TI  - Combination gene delivery of the cell cycle inhibitor p27 with thymidine kinase
      enhances prodrug cytotoxicity.
AB  - Cytoxicity induced by the herpesvirus thymidine kinase (TK) gene in combination
      with prodrugs is dependent on cell growth and leads to the elimination of
      genetically modified cells, thus limiting the duration of expression and efficacy
      of this treatment in vivo. Here, an effort was made to enhance TK/prodrug
      efficacy by coexpression of a cyclin-dependent kinase inhibitor (CKI), p27, to
      render cells resistant to TK/prodrug by inhibiting DNA synthesis. Expression of
      p27 by transfection substantially reduced cell cycle progression, and its
      activity was enhanced by mutations designed to stabilize the protein.
      Coexpression of p27 and TK or a p27/TK fusion protein led to greater prodrug
      cytotoxicity than that produced by TK alone in the Renca cell line, which is
      sensitive to bystander killing. Combination gene transfer of this CKI with TK
      therefore sustained the synthesis of TK by genetically modified cells to enhance
      the susceptibility of bystander cells to prodrug cytotoxicity and increased the
      efficacy of this gene transfer approach.

PMID- 9765468
TI  - Evidence for an underlying CD4 helper and CD8 T-cell defect in B-cell-deficient
      mice: failure to clear persistent virus infection after adoptive immunotherapy
      with virus-specific memory cells from muMT/muMT mice.
AB  - Adoptive transfer of virus-specific memory lymphocytes can be used to identify
      factors and mechanisms involved in the clearance of persistent virus infections.
      To analyze the role of B cells in clearing persistent infection with lymphocytic
      choriomeningitis virus (LCMV), we used B-cell-deficient muMT/muMT (B-/-) mice. B
      /- mice controlled an acute LCMV infection with the same kinetics and efficiency
      as B-cell-competent (B+/+) mice via virus-specific, major histocompatibility
      complex (MHC) class I-restricted CD8(+) cytotoxic T lymphocytes (CTL). CTL from B
      /- and B+/+ mice were equivalent in affinity to known LCMV CTL epitopes and had
      similar CTL precursor frequencies (pCTL). Adoptive transfer of memory cells from
      B+/+ mice led to virus clearance from persistently infected B+/+ recipients even
      after in vitro depletion of B cells, indicating that B cells or immunoglobulins
      are not required in the transfer population. In contrast, transfer of memory
      splenocytes from B-/- mice failed to clear virus. Control of virus was restored
      neither by transferring higher numbers of pCTL nor by supplementing B-/- memory
      splenocytes with LCMV-immune B cells or immune sera. Instead, B-/- mice were
      found to have a profound CD4 helper defect. Furthermore, compared to cultured
      splenocytes from B+/+ mice, those from B-/- mice secreted less gamma interferon
      (IFN-gamma) and interleukin 2, with differences most pronounced for CD8 T cells.
      While emphasizing the importance of CD4 T-cell help and IFN-gamma in the control
      of persistent infections, the CD4 T-helper and CD8 T-cell defects in B-/- mice
      suggest that B cells contribute to the induction of competent T effector cells.

PMID- 9765469
TI  - The 5' and 3' TAR elements of human immunodeficiency virus exert effects at
      several points in the virus life cycle.
AB  - The human immunodeficiency virus type 1 RNA genome contains a terminal repeat (R)
      sequence that encodes the TAR hairpin motif, which has been implicated in Tat
      mediated activation of transcription. More recently, a variety of other functions
      have been proposed for this structured RNA element. To determine the replicative
      roles of the 5' and 3' TAR hairpins, we analyzed multiple steps in the life cycle
      of wild-type and mutant viruses. A structure-destabilizing mutation was
      introduced in either the 5', the 3', or both TAR motifs of the proviral genome.
      As expected, opening of the 5' TAR hairpin caused a transcription defect. Because
      the level of protein expression was not similarly reduced, the translation of
      this mRNA was improved. No effect of the 3' hairpin on transcription and
      translation was measured. Mutations of the 5' and 3' hairpin structures reduced
      the efficiency of RNA packaging to similar extents, and RNA packaging was further
      reduced in the 5' and 3' TAR double mutant. Upon infection of cells with these
      virions, a reduced amount of reverse transcription products was synthesized by
      the TAR mutant. However, no net reverse transcription defect was observed after
      correction for the reduced level of virion RNA. This result was confirmed in in
      vitro reverse transcription assays. These data indicate that the 5' and 3' TAR
      motifs play important roles in several steps of the replication cycle, but these
      structures have no significant effect on the mechanism of reverse transcription.

PMID- 9765470
TI  - Molecular evidence for distinct genotypes of monkey B virus (herpesvirus simiae)
      which are related to the macaque host species.
AB  - Although monkey B virus (herpesvirus simiae; BV) is common in all macaque
      species, fatal human infections appear to be associated with exposure to rhesus
      macaques (Macaca mulatta), suggesting that BV isolates from rhesus monkeys may be
      more lethal to nonmacaques than are BV strains indigenous to other macaque
      species. To determine if significant differences that would support this
      supposition exist among BV isolates, we compared multiple BV strains isolated
      from rhesus, cynomolgus, pigtail, and Japanese macaques. Antigenic analyses
      indicated that while the isolates were very closely related to one another, there
      are some antigenic determinants that are specific to BV isolates from different
      macaque species. Restriction enzyme digest patterns of viral DNA revealed marked
      similarities between rhesus and Japanese macaque isolates, while pigtail and
      cynomolgus macaque isolates had distinctive cleavage patterns. To further compare
      genetic diversity among BV isolates, DNA sequences from two regions of the viral
      genome containing genes that are conserved (UL27 and US6) and variable (US4 and
      US5) among primate alphaherpesviruses, as well as from two noncoding intergenic
      regions, were determined. From these sequence data and a phylogenetic analysis of
      them it was evident that while all isolates were closely related strains of BV,
      there were three distinct genotypes. The three BV genotypes were directly related
      to the macaque species of origin and were composed of (i) isolates from rhesus
      and Japanese macaques, (ii) cynomolgus monkey isolates, and (iii) isolates from
      pigtail macaques. This study demonstrates the existence of different BV genotypes
      which are related to the macaque host species and thus provides a molecular basis
      for the possible existence of BV isolates which vary in their levels of
      pathogenicity for nonmacaque species.

PMID- 9765471
TI  - Subunit rotavirus vaccine administered parenterally to rabbits induces active
      protective immunity.
AB  - Virus-like particles (VLPs) are being evaluated as a candidate rotavirus vaccine.
      The immunogenicity and protective efficacy of different formulations of VLPs
      administered parenterally to rabbits were tested. Two doses of VLPs (2/6-, G3
      2/6/7-, or P[2], G3 2/4/6/7-VLPs) or SA11 simian rotavirus in Freund's adjuvants,
      QS-21 (saponin adjuvant), or aluminum phosphate (AlP) were administered.
      Serological and mucosal immune responses were evaluated in all vaccinated and
      control rabbits before and after oral challenge with 10(3) 50% infective doses of
      live P[14], G3 ALA lapine rotavirus. All VLP- and SA11-vaccinated rabbits
      developed high levels of rotavirus-specific serum and intestinal immunoglobulin G
      (IgG) antibodies but not intestinal IgA antibodies. SA11 and 2/4/6/7-VLPs
      afforded similar but much higher mean levels of protection than 2/6/7- or 2/6
      VLPs in QS-21. The presence of neutralizing antibodies to VP4 correlated (P <
      0.001, r = 0.55; Pearson's correlation coefficient) with enhanced protection
      rates, suggesting that these antibodies are important for protection. Although
      the inclusion of VP4 resulted in higher mean protection levels, high levels of
      protection (87 to 100%) from infection were observed in individual rabbits
      immunized with 2/6/7- or 2/6-VLPs in Freund's adjuvants. Therefore, neither VP7
      nor VP4 was absolutely required to achieve protection from infection in the
      rabbit model when Freund's adjuvant was used. Our results show that VLPs are
      immunogenic when administered parenterally to rabbits and that Freund's adjuvant
      is a better adjuvant than QS-21. The use of the rabbit model may help further our
      understanding of the critical rotavirus proteins needed to induce active
      protection. VLPs are a promising candidate for a parenterally administered
      subunit rotavirus vaccine.

PMID- 9765472
TI  - The bipartite geminivirus coat protein aids BR1 function in viral movement by
      affecting the accumulation of viral single-stranded DNA.
AB  - The movement of bipartite geminiviruses such as squash leaf curl virus (SqLCV)
      requires the cooperative interaction of two essential virus-encoded movement
      proteins, BR1 and BL1. While the viral coat protein AR1 is not essential for
      systemic infection, genetic studies demonstrate that its presence masks the
      defective phenotype of certain BR1 missense mutants, thus suggesting that coat
      protein does interact with the viral movement pathway. To further examine the
      mechanism of this interaction, we have constructed alanine-scanning mutants of
      AR1 and studied them for the ability to mask the infectivity defects of
      appropriate BR1 mutants, for the ability to target to the nucleus and to bind
      viral single-stranded DNA (ssDNA) and multimerize, and for effects on the
      accumulation of replicated viral ssDNA. We identified a specific region of AR1
      required for masking of appropriate BR1 mutants and showed that this same region
      of AR1 was also important for ssDNA binding and the accumulation of viral
      replicated ssDNA. This region of AR1 also overlapped that involved in
      multimerization of the coat protein. We also found that the accumulation in
      protoplasts of single-stranded forms of a recombinant plasmid that included the
      SqLCV replication origin but was too large to be encapsidated was dependent on
      the presence of AR1 but did not appear to require encapsidation. These findings
      extend our model for SqLCV movement, demonstrating that coat protein affects
      viral movement through its ability to induce the accumulation of replicated viral
      ssDNA genomes. They further suggested that encapsidation was not required for the
      AR1-dependent accumulation of viral ssDNA.

PMID- 9765473
TI  - Adenovirus induction of an interferon-regulatory factor during entry into the
      late phase of infection.
AB  - Virus infection of animal cells can induce intracellular antiviral responses
      mediated by the induction of interferon-regulatory transcription factors (IRFs),
      which bind to and control genes directed by the interferon-stimulated response
      element (ISRE). The purpose of this study was to determine whether adenovirus
      (Ad) induces IRFs during infection, because they might play a role in promoting
      viral pathogenesis. Here we show that after the late phase of infection, Ad
      induces a transcription factor related to the IRF family of factors. The IRF is
      induced shortly after Ad entry into late phase and is shown to stimulate ISRE
      directed transcription, to require activation by protein tyrosine kinase
      signalling, and to be induced several hours prior to the inhibition of cell
      protein synthesis. Inhibition of tyrosine kinase activity blocks Ad induction and
      activation of the IRF. Attempts to identify the Ad-induced factor immunologically
      and by photo-UV cross-linking indicate that it is likely a novel member of the
      IRF family. Finally, several independent lines of evidence also suggest that Ad
      induction of the IRF might correlate with the ability of the virus to block host
      cell protein synthesis later during infection.

PMID- 9765474
TI  - Inhibition of NF-kappaB activation in combination with bcl-2 expression allows
      for persistence of first-generation adenovirus vectors in the mouse liver.
AB  - NF-kappaB is a key regulator of the innate antiviral immune response, due in part
      to its transcriptional activation of cytokines and adhesion molecules, which, in
      turn, function in chemotaxis and activation of inflammatory cells. We reported
      earlier that viral gene expression in hepatocytes transduced with first
      generation (E1-deleted) adenoviruses induced NF-kappaB activation, elevation of
      serum cytokines, and hepatocellular apoptosis during the first days postinfusion.
      These events did not occur in mice infused with an adenovirus vector deleted for
      E1, E2, E3, and late gene expression. In the present study, we used an adenovirus
      expressing an IkappaBalpha supersuppressor (Ad.IkappaBM) and bcl-2 transgenic
      mice to unravel the role of virus-induced NF-kappaB activation and apoptosis in
      the clearance of recombinant adenovirus vectors from the liver. The combined
      action of IkappaBM and Bcl-2 allowed for vector persistence in livers of C57BL/6
      x C3H mice. In the absence of Bcl-2, IkappaBM expression in mouse livers
      significantly reduced NF-kappaB activation, cytokine expression, leukocyte
      infiltration, and the humoral immune response against the transgene product;
      however, this was not sufficient to prevent the decline of vector DNA in
      transduced cells. Infusion of Ad.IkappaBM caused extended apoptosis predominantly
      in periportal liver regions, indicating that NF-kappaB activation may protect
      transduced hepatocytes from apoptosis induced by adenovirus gene products. To
      confer vector persistence, bcl-2 transgene expression was required to block virus
      induced apoptosis if NF-kappaB protection was inactivated by IkappaBM. Expression
      of gene products involved in early stages of apoptotic pathways was up-regulated
      in response to virus infusion in bcl-2 transgenic mice, which may represent a
      compensatory effect. Our study supports the idea that the suppression of innate
      defense mechanisms improves vector persistence.

PMID- 9765475
TI  - Transcriptional organization of the avian adenovirus CELO.
AB  - A detailed map of the transcriptional organization of the CELO virus genome was
      produced. Recent computer analysis of CELO virus has indicated the presence of 38
      putative open reading frames (ORFs). This study, based on analysis of the
      transcriptional products of CELO in vitro, confirmed the presence of RNAs for 26
      of these 38 ORFs. All of the results were obtained by cDNA isolation or specific
      reverse transcriptase PCR. Observation of ORF transcription kinetics
      postinfection revealed the existence of early and late expression, with the
      earliest starting at 2 h postinfection. The 5' untranslated regions of some RNAs
      were also studied, and this revealed the existence of a bipartite leader
      sequence, comparable in structure to the tripartite leader of mastadenovirus. The
      leader most probably involved in transcriptional activity was observed in most of
      the structural protein genes of the CELO virus genome. This suggests some
      homology in transcriptional organization between the avian adenovirus CELO and
      known mastadenoviruses such as human adenovirus.

PMID- 9765476
TI  - Murine coronavirus-induced subacute fatal peritonitis in C57BL/6 mice deficient
      in gamma interferon.
AB  - Gamma interferon-deficient (IFN-gamma-/-) mice with a C57BL/6 background were
      infected intraperitoneally with mouse hepatitis virus strain JHM (JHMV). In
      contrast to IFN-gamma-+/- and IFN-gamma+/+ mice, JHMV persisted in IFN-gamma-/-
      mice and induced death during the subacute phase of the infection. Unexpectedly,
      infected IFN-gamma-/- mice showed severe peritonitis accompanying the
      accumulation of a viscous fluid in the abdominal and thoracic cavities in the
      subacute phase. Destructive changes of hepatocytes were not observed.
      Administration of recombinant IFN-gamma protracted the survival time of IFN-gamma
      /- mice after JHMV infection. These results demonstrate that IFN-gamma plays a
      critical role in viral clearance in JHMV infection. They also show that a
      resultant persistent JHMV infection induces another form of disease in IFN-gamma
      /- mice, which bears a resemblance to feline infectious peritonitis in cats.

PMID- 9765477
TI  - Equine endothelial cells support productive infection of equine infectious anemia
      virus.
AB  - Previous cell infectivity studies have demonstrated that the lentivirus equine
      infectious anemia virus (EIAV) infects tissue macrophages in vivo and in vitro.
      In addition, some strains of EIAV replicate to high titer in vitro in equine
      fibroblasts and fibroblast cell lines. Here we report a new cell type,
      macrovascular endothelial cells, that is infectible with EIAV. We tested the
      ability of EIAV to infect purified endothelial cells isolated from equine
      umbilical cords and renal arteries. Infectivity was detected by cell supernatant
      reverse transcriptase positivity, EIAV antigen positivity within individual
      cells, and the detection of viral RNA by in situ hybridization. Virus could
      rapidly spread through the endothelial cultures, and the supernatants of infected
      cultures contained high titers of infectious virus. There was no demonstrable
      cell killing in infected cultures. Three of four strains of EIAV that were tested
      replicated in these cultures, including MA-1, a fibroblast-tropic strain, Th.1, a
      macrophage-tropic strain, and WSU5, a strain that is fibroblast tropic and can
      cause disease. Finally, upon necropsy of a WSU5-infected horse 4 years
      postinfection, EIAV-positive endothelial cells were detected in outgrowths of
      renal artery cultures. These findings identify a new cell type that is infectible
      with EIAV. The role of endothelial cell infection in the course of equine
      infectious anemia is currently unknown, but endothelial cell infection may be
      involved in the edema that can be associated with infection. Furthermore, the
      ability of EIAV to persistently infect endothelial cultures and the presence of
      virus in endothelial cells from a long-term carrier suggest that this cell type
      can serve as a reservoir for the virus during subclinical phases of infection.

PMID- 9765478
TI  - Development of a heterologous model in germfree suckling rats for studies of
      rotavirus diarrhea.
AB  - Germfree suckling rats were infected with an SA11 rotavirus strain. Infected pups
      developed diarrhea associated with histopathological changes. The virus was
      detected in feces and in the small intestine. Cellular vacuolation was observed
      in the villi of the jejunum. These results provide a new model for further
      investigations of group A rotavirus infection.

PMID- 9765479
TI  - Use of a prenylation inhibitor as a novel antiviral agent.
AB  - No specific therapy exists for hepatitis delta virus (HDV), which can cause
      severe liver disease. Molecular genetic studies have implicated the prenylation
      site of large delta antigen as a critical determinant of HDV particle assembly.
      We have established a cell culture model which produces HDV-like particles, and
      we show that delta antigen prenylation can be pharmacologically inhibited by the
      prenylation inhibitor BZA-5B. Furthermore, BZA-5B specifically abolishes particle
      production in a dose-dependent manner. These results demonstrate that the use of
      such a prenylation inhibitor-based antiviral therapy may be feasible and identify
      a novel class of potential antiviral agents.

PMID- 9765480
TI  - Chemokine coreceptor usage by diverse primary isolates of human immunodeficiency
      virus type 1.
AB  - We tested chemokine receptor subset usage by diverse, well-characterized primary
      viruses isolated from peripheral blood by monitoring viral replication with CCR1,
      CCR2b, CCR3, CCR5, and CXCR4 U87MG.CD4 transformed cell lines and
      STRL33/BONZO/TYMSTR and GPR15/BOB HOS.CD4 transformed cell lines. Primary viruses
      were isolated from 79 men with confirmed human immunodeficiency virus type 1 (HIV
      1) infection from the Chicago component of the Multicenter AIDS Cohort Study at
      interval time points. Thirty-five additional well-characterized primary viruses
      representing HIV-1 group M subtypes A, B, C, D, and E and group O and three
      primary simian immunodeficiency virus (SIV) isolates were also used for these
      studies. The restricted use of the CCR5 chemokine receptor for viral entry was
      associated with infection by a virus having a non-syncytium-inducing phenotype
      and correlated with a reduced rate of disease progression and a prolonged disease
      free interval. Conversely, broadening chemokine receptor usage from CCR5 to both
      CCR5 and CXCR4 was associated with infection by a virus having a syncytium
      inducing phenotype and correlated with a faster rate of CD4 T-cell decline and
      progression of disease. We also observed a greater tendency for infection with a
      virus having a syncytium-inducing phenotype in men heterozygous for the defective
      CCR5 Delta32 allele (25%) than in those men homozygous for the wild-type CCR5
      allele (6%) (P = 0.03). The propensity for infection with a virus having a
      syncytium-inducing phenotype provides a partial explanation for the rapid disease
      progression among some men heterozygous for the defective CCR5 Delta32 allele.
      Furthermore, we did not identify any primary viruses that used CCR3 as an entry
      cofactor, despite this CC chemokine receptor being expressed on the cell surface
      at a level commensurate with or higher than that observed for primary peripheral
      blood mononuclear cells. Whereas isolates of primary viruses of SIV also used
      STRL33/BONZO/TYMSTR and GPR15/BOB, no primary isolates of HIV-1 used these
      particular chemokine receptor-like orphan molecules as entry cofactors,
      suggesting a limited contribution of these other chemokine receptors to viral
      evolution. Thus, despite the number of chemokine receptors implicated in viral
      entry, CCR5 and CXCR4 are likely to be the physiologically relevant chemokine
      receptors used as entry cofactors in vivo by diverse strains of primary viruses
      isolated from blood.

PMID- 9765481
TI  - The C-terminal half of the human immunodeficiency virus type 1 Gag precursor is
      sufficient for efficient particle assembly.
AB  - Human immunodeficiency virus type 1 particle assembly is directed by the Gag
      polyprotein Pr55(gag), the precursor for the matrix (MA), capsid (CA), and
      nucleocapsid proteins of the mature virion. We now show that CA sequences N
      terminal to the major homology region (MHR), which form a distinct domain, are
      dispensable for particle formation. However, slightly larger deletions which
      extend into the MHR severely impair particle production. Remarkably, a deletion
      which removed essentially all MA and CA sequences between the N-terminal myristyl
      anchor and the MHR reduced the yield of extracellular particles only moderately.
      Particle formation even exceeded wild-type levels when additional MA sequences,
      either from the N or the C terminus of the domain, were retained. We conclude
      that no distinct region between the myristyl anchor and the MHR is required for
      efficient particle assembly or release.

PMID- 9765482
TI  - A map of interactions between the proteins of a retrotransposon.
AB  - The yeast two-hybrid system and in vitro binding assays were used to characterize
      54 potential interactions between the proteins of Tf1, an LTR-retrotransposon
      found in Schizosaccharomyces pombe. The Tf1 integrase (IN) protein was found to
      interact strongly with itself and not with other control proteins. In addition,
      the IN core domain interacted strongly with itself and full-length IN.
      Interestingly, the two-hybrid analysis detected an interaction between the RNase
      H domain of reverse transcriptase and IN. The biological implications of these
      interactions are discussed.

PMID- 9765483
TI  - Epstein-Barr virus small RNA (EBER) genes: differential regulation during lytic
      viral replication.
AB  - In every latently Epstein-Barr virus-infected cell the viral genes EBER-1 and
      EBER-2 are transcribed by polymerase III. In lytically infected cells in vivo the
      EBER genes could not be detected. However, in cell culture downregulation could
      not be confirmed, and hence the relevance of this shutdown to the replication of
      the virus was not clear. We assayed the transcriptional activity of the EBER
      genes by nuclear run-on assays with enriched lytically infected cells and
      demonstrated that EBER-1 and EBER-2 are differentially downregulated on the
      transcriptional level during the switch to lytic viral replication. This
      downregulation was an early event during the lytic replication of the virus.

PMID- 9765484
TI  - Level of ICAM-1 surface expression on virus producer cells influences both the
      amount of virion-bound host ICAM-1 and human immunodeficiency virus type 1
      infectivity.
AB  - Using virions harvested from 293T cells stably expressing either low or high
      levels of surface ICAM-1, we determined that the number of virus-embedded host
      ICAM-1 proteins is positively influenced by the expression level of ICAM-1 on
      virus producer cells. Moreover, the increase in virion-bound host cell membrane
      ICAM-1 led to a concomitant enhancement of virus infectivity when a T-cell-tropic
      strain of human immunodeficiency virus type 1 (HIV-1) was used. The phenomenon
      was also seen when primary human cells were infected with virions pseudotyped
      with the envelope protein from a macrophage-tropic HIV-1 isolate, thus ruling out
      any envelope-specific effect. We also observed that target cells treated with NKI
      L16, an anti-LFA-1 antibody known to increase the affinity of LFA-1 for ICAM-1,
      were markedly more susceptible to infection with HIV-1 particles bearing on their
      surfaces large numbers of host-derived ICAM-1 proteins. Given that cellular
      activation of leukocytes is known to modify the conformational state of LFA-1 and
      induce ICAM-1 surface expression, it is tempting to speculate that activation of
      virus-infected cells will lead to the production of HIV-1 particles bearing more
      host ICAM-1 on their surfaces and that such progeny virions will preferentially
      infect and replicate more efficiently in activated cells which are prevalent in
      lymphoid organs.

PMID- 9765485
TI  - Use of coreceptors other than CCR5 by non-syncytium-inducing adult and pediatric
      isolates of human immunodeficiency virus type 1 is rare in vitro.
AB  - We have tested a panel of pediatric and adult human immunodeficiency virus type 1
      (HIV-1) primary isolates for the ability to employ the following proteins as
      coreceptors during viral entry: CCR1, CCR2b, CCR3, CCR4, CCR5, CCR8, CXCR4,
      Bonzo, BOB, GPR1, V28, US28, and APJ. Most non-syncytium-inducing isolates could
      utilize only CCR5. All syncytium-inducing viruses used CXCR4, some also employed
      V28, and one (DH123) used CCR8 and APJ as well. A longitudinal series of HIV-1
      subtype B isolates from an infected infant and its mother utilized Bonzo
      efficiently, as well as CCR5. The maternal isolates, which were syncytium
      inducing, also used CXCR4, CCR8, V28, and APJ.

PMID- 9765486
TI  - CD4(+) T-lymphocyte depletion in human lymphoid tissue ex vivo is not induced by
      noninfectious human immunodeficiency virus type 1 virions.
AB  - We tested infectious human immunodeficiency virus type 1 (HIV-1), noninfectious
      but conformationally authentic inactivated whole HIV-1 virions, and purified
      gp120 for the ability to induce depletion of CD4(+) T cells in human lymphoid
      tissues ex vivo. Infectious CXCR4-tropic HIV-1, but not matched inactivated
      virions or gp120, mediated CD4(+) T-cell depletion, consistent with mechanisms
      requiring productive infection.

PMID- 9765487
TI  - Attachment and growth of human rotaviruses RV-3 and S12/85 in Caco-2 cells depend
      on VP4.
AB  - Studies with human neonatal rotaviruses RV-3 and S12/85 and their reassortants
      showed that VP4 is a determinant of rotavirus attachment to and growth in Caco-2
      cells. The binding of these viruses to MA104 and Caco-2 cells correlated with
      their growth ability. Virus sensitivity to trypsin and the VP4 fusion region may
      be implicated in these processes.

PMID- 9765488
TI  - Roles of the human immunodeficiency virus type 1 nucleocapsid protein in
      annealing and initiation versus elongation in reverse transcription of viral
      negative-strand strong-stop DNA.
AB  - To study the initiation of human immunodeficiency virus type 1 reverse
      transcription, we have used the viral nucleocapsid protein (NC7) to anneal
      tRNA3Lys primer onto viral genomic RNA and have then eliminated NC7 from this
      primer-template complex by digestion with proteinase K and phenol-chloroform
      extraction of residual protein. Our data show that saturating concentrations of
      NC7 resulted in the formation of an active tRNA-template complex that yielded
      enhanced production of full-length negative-strand strong-stop DNA [(-)ssDNA] and
      that this complex remained active even after the elimination of NC7. While both
      of the two Zn finger motifs found within NC7 were essential for efficient
      elongation, NC protein that contained a point mutation in the first Zn finger or
      that was devoid of both Zn fingers yielded primer-template complexes that could
      still be initiated in 1-base-extension assays. In contrast, the use of heat
      annealing to produce primer-template complexes resulted in proportions of full
      length (-)ssDNA lower than those seen with NC protein, and the addition of NC
      protein to such preformed primer-template complexes was able to reverse this
      defect only to a marginal extent.

PMID- 9765489
TI  - Metabolic labeling of woodchuck hepatitis B virus X protein in naturally infected
      hepatocytes reveals a bimodal half-life and association with the nuclear
      framework.
AB  - In order to identify potential sites of hepadnavirus X protein action, we have
      investigated the subcellular distribution and the stability of woodchuck
      hepatitis virus (WHV) X protein (WHx) in primary hepatocytes isolated from
      woodchucks with persistent WHV infection. In vivo cell labeling and cell
      fractionation studies showed that the majority of WHx is a soluble cytoplasmic
      protein while a minor part of newly synthesized WHx is associated with a nuclear
      framework fraction (20%) and with cytoskeletal components (5 to 10%). Pulse-chase
      experiments revealed that cytoplasmic WHx has a short half-life and decays with
      bimodal kinetics (approximately 20 min and 3 h). The rates of association and
      turnover of nucleus-associated WHx suggest that compartmentalization may be
      responsible for the bimodal turnover observed in the cytoplasm.

PMID- 9765491
TI  - The P2 protein of rice dwarf phytoreovirus is required for adsorption of the
      virus to cells of the insect vector.
AB  - Intact particles of rice dwarf phytoreovirus adsorbed to and entered monolayer
      cultured cells of the insect vector Nephotettix cincticeps and multiplied within
      the cells. Particles that lacked the P2 protein neither attached to nor infected
      such cells. Furthermore, P2-free particles obtained from a transmission-competent
      isolate of the virus were unable to infect insect vectors that had been allowed
      to feed on these virus particles through a membrane. However, when such virus
      particles were injected into insects via a glass capillary tube they successfully
      infected the insects, which became able to transmit the virus. These results
      support the hypothesis that, while P2-free particles can neither interact with
      nor infect cells in the intestinal tract of the insect vector, they do retain the
      ability to infect such cells when physically introduced into the hemolymph by
      injection.

PMID- 9765490
TI  - Identification and characterization of an RNA-dependent RNA polymerase activity
      within the nonstructural protein 5B region of bovine viral diarrhea virus.
AB  - Nonstructural protein 5B (NS5B) of bovine viral diarrhea virus (BVDV) contains
      sequence motifs that are predictive of an RNA-dependent RNA polymerase activity.
      We describe the expression and purification of the BVDV NS5B protein derived from
      an infectious cDNA clone of BVDV (NADL strain). BVDV NS5B protein was active in
      an in vitro RNA polymerase assay using homopolymeric RNA or BVDV minigenomic RNA
      templates. The major product was a covalently linked double-stranded molecule
      generated by a "copy-back" mechanism from the input template RNA. In addition, a
      nucleotide-nonspecific and template-independent terminal nucleotidyl transferase
      activity was observed with the BVDV NS5B preparation.

PMID- 9765492
TI  - RNA-binding activity of the E1B 55-kilodalton protein from human adenovirus type
      5.
AB  - The human adenovirus 5 E1B 55-kDa protein is required for efficient
      nucleocytoplasmic transport of late viral mRNAs. This protein is shown to have
      RNA-binding activity which maps to a region of the protein with homology to a
      family of RNA-binding proteins and which has been shown previously to be
      essential for functionality of the protein in vivo.

PMID- 9765493
TI  - Short consensus repeat domain 1 of decay-accelerating factor is required for
      enterovirus 70 binding.
AB  - Enterovirus 70 (EV70), like several other human enteroviruses, can utilize decay
      accelerating factor (DAF [CD55]) as an attachment protein. Using chimeric
      molecules composed of different combinations of the short consensus repeat
      domains (SCRs) of DAF and membrane cofactor protein (CD46), we show that
      sequences in SCR1 of DAF are essential for EV70 binding. Of the human
      enteroviruses that can bind to DAF, only EV70 and coxsackievirus A21 require
      sequences in SCR1 for this interaction.

PMID- 9765495
TI  - His1, an archaeal virus of the Fuselloviridae family that infects Haloarcula
      hispanica.
AB  - A novel archaeal virus, His1, was isolated from hypersaline waters in
      southeastern Australia. It was lytic, grew only on Haloarcula hispanica (titers
      of up to 10(11) PFU/ml), and displayed a lemon-shaped morphology (74 by 44 nm)
      previously reported only for a virus of the extreme thermophiles (SSV1). The
      density of His1 was approximately 1.28 g/ml, similar to that of SSV1 (1.24 g/ml).
      Purified particles were resistant to low salt concentrations. The genome was
      linear, double-stranded DNA of 14.9 kb, similar to the genome of SSV1 (15.5 kb).
      Morphologically, this isolate clearly belongs to the recently proposed
      Fuselloviridae family of archaeal viruses. It is the first member of this family
      from the extremely halophilic archaea, and its host, H. hispanica, can be readily
      manipulated genetically.

PMID- 9765494
TI  - Mapping of epitopes exposed on intact human immunodeficiency virus type 1 (HIV-1)
      virions: a new strategy for studying the immunologic relatedness of HIV-1.
AB  - To study the antigenic conservation of epitopes of human immunodeficiency virus
      type 1 (HIV-1) isolates of different clades, the abilities of human anti-HIV-1
      gp120 and gp41 monoclonal antibodies (MAbs) to bind to intact HIV-1 virions were
      determined by a newly developed virus-binding assay. Eighteen human anti-HIV
      MAbs, which were directed at the V2, V3 loop, CD4-binding domain (CD4bd), C5, or
      gp41 regions, were used. Nine HIV-1 isolates from clades A, B, D, F, G, and H
      were used. Microtiter wells were coated with the MAbs, after which virus was
      added. Bound virus was detected after lysis by testing for p24 antigen with a
      noncommercial p24 enzyme-linked immunosorbent assay. The anti-V3 MAbs strongly
      bound the four clade B viruses and viruses from the non-B clades, although
      binding was weaker and more sporadic with the latter. The degrees of binding by
      the anti-V3 MAbs to CXCR4- and CCR5-tropic viruses were similar, suggesting that
      the V3 loops of these two categories of viruses are similarly exposed. The anti
      C5 MAbs bound isolates of clades A, B, and D. Only weak and sporadic binding of
      all the viruses tested with anti-CD4bd, anti-V2, and anti-gp41 MAbs was detected.
      These results suggest that V3 and C5 structures are shared and well exposed on
      intact virions of different clades compared to the CD4bd, V2, and gp41 regions.

PMID- 9765497
TI  - Requirement for CD4(+) T cells in the Friend murine retrovirus neutralizing
      antibody response: evidence for functional T cells in genetic low-recovery mice.
AB  - Recovery from infection with the Friend murine leukemia retrovirus complex (FV)
      requires T-helper cells and cytotoxic T cells as well as neutralizing antibodies.
      Several host genes, including genes of the major histocompatibility complex (H-2)
      and an H-2-unlinked gene, Rfv-3, influence these FV-specific immune responses.
      (B10.A x A/Wy)F1 mice, which have the H-2(a/a) Rfv-3(r/s) genotype, fail to mount
      a detectable FV-specific T-cell proliferative response but nevertheless produce
      FV-specific neutralizing immunoglobulin M (IgM) antibodies and can eliminate FV
      viremia. Thus, this IgM response, primarily influenced by the Rfv-3 gene, may be
      T-cell independent. To test this idea, mice were depleted of either CD4(+) or
      CD8(+) T-cell populations in vivo and were monitored for the effect on the
      neutralizing antibody response following FV infection. Surprisingly, mice in
      which CD4(+) cells were depleted showed undetectable FV-neutralizing antibody
      responses and high viremia levels compared to nondepleted or CD8-depleted
      animals. In addition to knocking out the FV antibody response, CD4(+) T-cell
      depletion reduced survival time significantly, further indicating the importance
      of CD4(+) T cells. These studies revealed the first evidence for a functional T
      cell response following FV infection in these low-recovery mice and showed that
      CD4(+) T-helper cells are required for the Rfv-3-controlled FV antibody response.

PMID- 9765496
TI  - The human T-cell leukemia virus type 1 oncoprotein Tax inhibits the
      transcriptional activity of c-Myb through competition for the CREB binding
      protein.
AB  - Tax, the transforming protein of human T-cell leukemia virus type 1 (HTLV-1), is
      required for strong activation of HTLV-1 transcription. This activation is
      mediated through interaction with the KIX domain of the cellular coactivator CREB
      binding protein (CBP). In this study we examined the possibility that the Tax-KIX
      interaction may mediate effects on cellular gene transcription in vivo, as a
      growing number of cellular transcription factors have been shown to utilize CBP
      as a coactivator. We tested the ability of Tax to deregulate the activity of the
      cellular transcription factor, c-Myb, since both Tax and c-Myb interact with the
      KIX domain of CBP. Our results show that in vivo, Tax antagonizes the
      transcriptional activity of c-Myb and, reciprocally, c-Myb antagonizes the
      transcriptional activity of Tax. Furthermore, c-Myb competes for KIX binding to
      Tax in vitro, indicating that these two transcription factors bind CBP in a
      mutually exclusive manner. This novel mechanism of transcriptional interference
      by Tax may promote globally deregulated cellular gene expression in the HTLV-1
      infected cell, possibly leading to leukemogenesis.

PMID- 9765498
TI  - Definition of amino acid residues on the epitope responsible for recognition by
      influenza A virus H1-specific, H2-specific, and H1- and H2-cross-reactive murine
      cytotoxic T-lymphocyte clones.
AB  - We defined the epitopes recognized by three influenza A virus-specific, H-2Kd
      restricted CD8(+) cytotoxic T-lymphocyte (CTL) clones: H1-specific clone A-12, H2
      specific clone F-4, and H1- and H2-cross-reactive clone B7-B7. The A-12 and B7-B7
      clones recognized the same peptide, which comprises amino acids 533 to 541
      (IYSTVASSL) of A/PR/8 hemagglutinin (HA). The F-4 and B7-B7 clones both
      recognized the peptide which comprise amino acids 529 to 537 (IYATVAGSL) of A/Jap
      HA. Amino acids 533 to 541 of A/PR/8 HA are compatible with amino acids 529 to
      537 of A/Jap HA. Amino acid S at positions 3 and 7 was responsible for
      recognition by H1-specific clone A-12, while amino acid G at position 7 was
      responsible for recognition by H2-specific clone F-4. Two conserved amino acids,
      T at position 4 and A at position 6, were responsible for recognition by H1-, and
      H2-cross-reactive clone B7-B7. These results indicate that a single nine-amino
      acid region is recognized by HA-specific CTL clones of three different subtype
      specificities and that the amino acids responsible for the recognition by the CTL
      clones are different.

PMID- 9765499
TI  - Viral cell entry induced by cross-linked decay-accelerating factor.
AB  - Decay-accelerating factor (DAF) mediates cellular attachment for many human
      picornaviruses. In most cases, viral binding to DAF is itself insufficient to
      permit cell infectivity, with a second, functional internalization receptor being
      required to facilitate this process. Previously, we postulated that the role of
      DAF in enterovirus cell infection is as a sequestration receptor, maintaining a
      reservoir of bound virus in an infectious state, awaiting interaction with
      functional internalization receptors. Many of these functional receptors possess
      the capacity to induce relatively rapid changes in capsid conformations,
      resulting in the formation of altered particles (A-type particles). In this
      report, we show that antibody-cross-linked DAF, in contrast to endogenous surface
      expressed forms, can act as a functional virus receptor to mediate coxsackie A21
      virus (CAV21) lytic cell infection. In contrast to the situation with ICAM-1
      mediated CAV21 infection, in which high levels of A-type particles are formed,
      cross-linked DAF-induced CAV21 replication occurs in the absence of detectable A
      particle formation.

PMID- 9765500
TI  - Mapping the prion protein using recombinant antibodies.
AB  - The fundamental event in prion disease is thought to be the posttranslational
      conversion of the cellular prion protein (PrPC) into a pathogenic isoform
      (PrPSc). The occurrence of PrPC on the cell surface and PrPSc in amyloid plaques
      in situ or in aggregates following purification complicates the study of the
      molecular events that underlie the disease process. Monoclonal antibodies are
      highly sensitive probes of protein conformation which can be used under these
      conditions. Here, we report the rescue of a diverse panel of 19 PrP-specific
      recombinant monoclonal antibodies from phage display libraries prepared from PrP
      deficient (Prnp0/0) mice immunized with infectious prions either in the form of
      rods or PrP 27-30 dispersed into liposomes. The antibodies recognize a number of
      distinct linear and discontinuous epitopes that are presented to a varying degree
      on different PrP preparations. The epitope reactivity of the recombinant PrP(90
      231) molecule was almost indistinguishable from that of PrPC on the cell surface,
      validating the importance of detailed structural studies on the recombinant
      molecule. Only one epitope region at the C terminus of PrP was well presented on
      both PrPC and PrPSc, while epitopes associated with most of the antibodies in the
      panel were present on PrPC but absent from PrPSc.

PMID- 9765501
TI  - The Caenorhabditis elegans gene T23G5.5 encodes an antidepressant- and cocaine
      sensitive dopamine transporter.
AB  - A small subset of neurons in the nematode Caenorhabditis elegans utilizes the
      catecholamine dopamine (DA) as a neurotransmitter to control or modulate movement
      and egg-laying. Disruption of DA-mediated behaviors represents a potentially
      powerful strategy to identify genes that are likely to participate in
      dopaminergic systems in man. In vertebrates, extracellular DA is inactivated by
      presynaptic DA transport proteins (DATs) that are also major targets of addictive
      agents, including amphetamines and cocaine. We used oligonucleotides derived from
      the C. elegans genomic locus T23G5.5 to isolate and characterize T23G5.5 cDNAs.
      Our studies predict that mRNAs from this locus encode a 615-amino-acid
      polypeptide with twelve stretches of hydrophobicity suitable for transmembrane
      domains, similar to that found in vertebrate catecholamine transporters. The
      inferred translation product bears highest identity (43-47%) to catecholamine
      (DA, norepinephrine, epinephrine) transporters within the GAT1/NET gene family
      and possesses conserved residues implicated in amine substrate recognition.
      Consistent with these findings, HeLa cells transfected with the C. elegans cDNA
      exhibit saturable and high affinity DA transport (Km = 1.2 microM) that is
      dependent on extracellular Na+ and Cl- and blocked by inhibitors of mammalian
      catecholamine transporters, including norepinephrine transporter- and DAT
      selective antagonists, tricyclic antidepressants, and the nonselective amine
      transporter antagonists cocaine and D-amphetamine. These studies validate the
      T23G5.5 locus as encoding a functional catecholamine transporter, providing
      important comparative sequence information for catecholamine transporter
      structure/function studies and a path to identify regulators of dopaminergic
      signaling via genetic or pharmacologic manipulation of C. elegans cDNA in vivo.

PMID- 9765502
TI  - Do specific or nonspecific interactions with proteins underlie inhalational
      anesthetic action?
AB  - To determine whether specific or nonspecific interactions between inhaled
      anesthetics and proteins are more likely to underlie anesthetic actions, analysis
      of hydrogen/tritium exchange was used to measure effects on the stability of two
      model proteins that had been previously shown to bind anesthetics specifically
      (bovine serum albumin) or only nonspecifically (myoglobin). The data indicated
      that stabilization of albumin correlated with the potencies of a wide range of
      anesthetic compounds significantly better than did destabilization of myoglobin.
      In addition, sensitivity to nonanesthetics, isoflurane stereoselectivity, and
      temperature and pressure effects all influenced the stabilization of bovine serum
      albumin, but not the destabilization of myoglobin, in a manner strongly
      supporting the premise that specific binding interactions with protein targets
      underlie anesthetic action. These observations significantly increase the
      likelihood that such interactions can be found and optimized.

PMID- 9765503
TI  - Identification of a key amino acid of the beta2-adrenergic receptor for high
      affinity binding of salmeterol.
AB  - Transmembrane domains (TMDs) I, II, and VII of the beta2-adrenergic receptor
      (beta2AR) were replaced, individually or in combination, with the corresponding
      regions of the beta1AR, and vice versa. The beta2-selective binding of salmeterol
      was not affected by the exchange of TMD I between the beta1- and beta2ARs. The
      affinity of salmeterol was slightly decreased (32-fold) by replacement of TMD II
      of the beta2AR with the homologous region of the beta1AR; the affinity was
      strongly decreased (1870-fold) for the beta2AR with TMD VII of the beta1AR. The
      affinity of salmeterol was partially restored by the introduction of TMD VII, but
      not TMD II, of the beta2AR into the beta1AR. By analyzing alanine-substituted
      mutants, we found that Tyr308 in TMD VII was mainly responsible for the high
      affinity binding of salmeterol. Two salmeterol derivatives with the ether oxygen
      at different positions in the side chain showed 33- and 64-fold decreased
      affinities for the wild-type beta2AR, and a derivative with no ether oxygen
      showed 147-fold decreased affinity for the wild-type beta2AR. These results
      indicate that Tyr308 in TMD VII is the major amino acid conferring the beta2
      selective binding of salmeterol to the beta2AR and that the position of the ether
      oxygen in the side chain is also important for beta2-selective binding. A three
      dimensional model of the salmeterol-beta2AR complex shows that the phenyl group
      of Tyr308 interacts with methylene groups near the protonated amine of salmeterol
      and the ether oxygen interacts with Tyr316.

PMID- 9765504
TI  - Analysis of random recombination between human MDR1 and mouse mdr1a cDNA in a
      pHaMDR-dihydrofolate reductase bicistronic expression system.
AB  - Human P-glycoprotein (Pgp) confers multidrug resistance (MDR) to otherwise
      sensitive cells. The homologous mouse Pgps, which are encoded by mouse mdr1a
      (also known as mdr3) and mdr1b (also known as mdr1), confer different degrees of
      resistance to the same MDR drugs and inhibitors. To create recombinants for the
      study of sequences responsible for these differences in drug-resistance, chimeric
      cDNA libraries can be constructed by homologous recombination of pools of related
      sequences. This mutagenesis approach is called DNA shuffling. To select for
      chimeric Pgp with an altered resistance profile, DNA shuffling between the
      homologous but not identical drug interacting transmembrane domains 5 and 6 of
      human MDR1 and mouse mdr1a was used. The chimeric proteins were expressed in
      human KB-3-1 cells. One recombinant Pgp (clone 3-4) with a novel phenotype was
      analyzed in detail. Inhibitors of Pgp, including verapamil and cyclosporin A,
      were less effective in reversing resistance of the chimeric Pgp compared with
      wild-type Pgp, for certain drugs. However, [125I]iodoarylazidoprazosin
      photoaffinity labeling of the chimeric Pgp and its binding competition with
      cyclosporin A, showed that cyclosporin A competed for the photoaffinity labeling.
      The chimeric Pgp cells stained less well with human-specific anti-Pgp mAb MRK16
      than wild-type Pgp, despite having the described epitopes for MRK16. Staining
      with human-specific mAb UIC2 was increased when the chimeric protein was compared
      with wild-type Pgp. These results suggest an alteration in exposure of human Pgp
      specific epitopes in this chimeric Pgp, as well as a change in the interaction of
      reversing agents with the chimeric protein.

PMID- 9765505
TI  - Protein synthesis is required for caspase activation and induction of apoptosis
      by bisphosphonate drugs.
AB  - The exact mechanisms of action of antiresorptive bisphosphonate drugs remain
      unclear, although they may inhibit bone resorption by mechanisms that can lead to
      osteoclast apoptosis. These drugs also cause apoptosis in J774 macrophages,
      probably as a consequence of inhibition of protein prenylation. However, the
      molecular pathways that lead to apoptosis are not known. In some cells, apoptosis
      induced by statins (other inhibitors of protein prenylation) is dependent on
      protein synthesis. The aim of this study was to further characterize the kinetics
      and biochemical features of bisphosphonate-induced apoptosis, including the
      dependence on protein synthesis. Alendronate-induced apoptosis in J774 cells
      occurred after approximately 16 hr of treatment, although shorter exposures to
      the drug followed by incubation in bisphosphonate-free medium also committed
      cells to apoptosis. The appearance of apoptotic cells was associated with the
      appearance of caspase-3-like activity. Apoptosis induced by bisphosphonate or
      mevastatin was found to be dependent on protein synthesis because cycloheximide
      inhibited chromatin condensation, DNA fragmentation and activation of caspase-3
      like protease or proteases. Protein synthesis was required for events that lead
      to commitment to apoptosis but not for the execution phase because cycloheximide
      did not prevent apoptosis when added >/=15 hr after the start of alendronate
      treatment. Furthermore, staurosporine-induced caspase-3-like activity and
      apoptosis in J774 cells could not be prevented by cycloheximide. These
      observations demonstrate that activation of caspase-3-like proteases and
      inhibition of commitment to apoptosis by cycloheximide are common features of
      apoptotic cell death induced by inhibitors of protein prenylation such as
      bisphosphonates.

PMID- 9765506
TI  - Activation of glycine and glutamate receptors increases intracellular calcium in
      cells derived from the endocrine pancreas.
AB  - We studied calcium signaling in a newly described pancreatic cell line, GK-P3,
      that expresses functional amino acid neurotransmitter receptors. GK-P3 cells
      express the first strychnine-sensitive glycine receptors reported in a permanent
      cell line. In addition, GK-P3 cells express alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA)-type glutamate receptors. Both types of amino acid
      receptors showed electrophysiological and pharmacological behavior similar to
      their neuronal counterparts. The glycine receptors were permeable to Cl- and
      blocked by the selective antagonist strychnine. AMPA receptors showed limited
      permeability to Ca2+, were blocked by 6-cyano-2, 3-dihydroxy-7-nitroquinoxaline,
      and were potentiated by cyclothiazide. Interestingly, activation of either
      receptor type increased intracellular Ca2+ measured by digital imaging of Fura-2
      fluorescence. These Ca2+ signals were completely blocked by 30 microM La3+,
      suggesting that the Ca2+ entered the cells largely through voltage-dependent Ca2+
      channels. Alterations in the extracellular concentrations of Cl- and/or HCO3- had
      only marginal effects on glycine-evoked Ca2+ signals. However, increases in
      intracellular Ca2+ mediated by AMPA receptors were absent when the extracellular
      Na+ was replaced with an impermeant cation, N-methyl-D-glucamine. We conclude
      that activation of ligand-gated cation or anion channels depolarize GK-P3 cells
      sufficiently to activate their voltage-gated Ca2+ channels leading to increases
      in intracellular Ca2+ concentration. Thus, glycine and glutamate receptors may
      regulate Ca2+-dependent secretory mechanisms in islet cells by altering the
      membrane potential of these cells. Our data in GK-P3 cells support the growing
      weight of evidence for a role of amino acid neurotransmitters in pancreatic
      islets and introduce strychnine-sensitive glycine receptors as a novel target of
      amino acid neurotransmitter regulation in islets.

PMID- 9765508
TI  - Chronic morphine augments G(beta)(gamma)/Gs(alpha) stimulation of adenylyl
      cyclase: relevance to opioid tolerance.
AB  - In the current study, we investigated the neurochemical basis for the previously
      reported predominance of stimulatory mu-opioid signaling in guinea pig
      longitudinal muscle/myenteric plexus (LMMP) preparations after chronic in vivo
      morphine exposure. As expected, recombinant Gsalpha (rGsalpha) dose-dependently
      stimulated adenylyl cyclase (AC) activity in LMMP membranes obtained from opioid
      naive as well as tolerant LMMP tissue. However, the magnitude of the increase was
      significantly greater in the latter than in the former. The Gbetagamma blocking
      peptide QEHA (50 microM) essentially abolished stimulation by rGsalpha in LMMP
      membranes obtained from both opioid naive and tolerant animals. Interestingly,
      after partial blockade by lower QEHA concentrations, the incremental AC
      stimulation by rGsalpha in tolerant LMMP membranes was no longer observed,
      indicating augmented Gbetagamma stimulatory responsiveness. Concomitant changes
      in the content of AC isoform protein are consistent with these biochemical
      observations. After chronic systemic morphine, AC protein is augmented
      significantly (56%). This increment is most likely to be composed of AC isoforms
      that are stimulated by Gbetagamma. This is the first demonstration in a complex
      mammalian tissue that persistent activation of opioid receptors results in
      augmented Gbetagamma/Gsalpha AC stimulatory interactiveness. The relevance of
      such changes to the manifestation of opioid tolerance is discussed.

PMID- 9765507
TI  - Polymorphic expression of the UDP-glucuronosyltransferase UGT1A gene locus in
      human gastric epithelium.
AB  - The human UDP-glucuronosyltransferase (UGT) 1A (UGT1A) locus is regulated in a
      tissue specific fashion in liver and extrahepatic tissues. Three extrahepatic
      UGT1A proteins, UGT1A7, UGT1A8, and UGT1A10, have been discovered and are
      believed to contribute to the diversity of extrahepatic glucuronidation. UGTs
      eliminate by glucuronidation a broad variety of endobiotic and xenobiotic
      substrates, which include bilirubin, therapeutic drugs, and carcinogens. Human
      gastric mucosa represents a primary location of tissue contact with dietary
      constituents, pharmaceutical drugs, and environmental carcinogens. To study the
      role and regulation of UGT1A gene products in stomach UGT1A mRNA expression and
      UGT catalytic activities were investigated in a panel of 14 normal gastric
      mucosa/adenocarcinoma sample pairs. UGT1A mRNA levels were differentially
      regulated in stomach, a feature not found in hepatic tissue. Normal gastric
      epithelium consistently expressed extrahepatic UGT1A7 and UGT1A10. However,
      polymorphic expression of UGT1A1 (29%), UGT1A3 (21%), and UGT1A6 (36%) was
      detected. Polymorphic UGT1A regulation was confirmed in adenocarcinoma samples
      with the additional observation of differential down-regulation of UGT1A1,
      UGT1A3, UGT1A6, and UGT1A10 and up-regulation of UGT1A7 mRNA. The polymorphic
      UGT1A regulation in stomach contrasts the homogeneous regulation of UGT1A gene
      products in human liver. Activity assays demonstrated 2- to 4-fold
      interindividual differences in UGT activity and qualitative differences between
      individuals. The polymorphic regulation of UGT1A gene products in gastric tissue
      may be the biological basis that determines interindividual differences in
      extrahepatic microsomal drug metabolism.

PMID- 9765509
TI  - Modulation of apoptosis in rat thymocytes by analogs of staurosporine: lack of
      direct association with inhibition of protein kinase C.
AB  - Protein kinase C (PKC) is an important constituent of the signaling pathways
      involved in apoptosis. The PKC inhibitor staurosporine induces apoptosis in many
      cell types. We characterized the role of PKC in the induction of apoptosis in
      immature rat thymocytes by investigating the effects of staurosporine with those
      of five analogs. Four of them, the indolocarbazoles CGP 41251 and UCN-01 and the
      bisindolylmaleimides RO 31-8220 and GF 109203X, possess high PKC-inhibitory
      specificity and potency, whereas one, the UCN-01 stereoisomer UCN-02, is a weak
      PKC inhibitor. Apoptosis was examined by flow cytometry, internucleosomal DNA
      cleavage, and formation of large DNA fragments. Staurosporine, UCN-01, and UCN-02
      induced a concentration- and time-dependent increase in apoptosis, whereas
      neither CGP 41251, RO 31-8220, nor GF 109203X induced apoptosis. The mechanism of
      induction of apoptosis by staurosporine, UCN-01, and UCN-02 was clearly different
      from the mechanism that mediates induction of apoptosis by etoposide and
      dexamethasone, as judged by differential effects of modulators of apoptosis.
      Staurosporine, UCN-01, and UCN-02 at concentrations of a hundredth to a
      thousandth of those at which they induced apoptosis, and RO 31-8220 inhibited
      apoptosis elicited by thapsigargin but not apoptosis caused by dexamethasone or
      etoposide. The results suggest that (i) UCN-01 and UCN-02 mimic staurosporine as
      inducers of thymocyte apoptosis; (ii) staurosporine, UCN-01 and UCN-02 share a
      biphasic effect on apoptosis in rat thymocytes, being inhibitory at low
      concentrations and stimulatory at high concentrations; and (iii) inhibition of
      PKC alone is insufficient for induction of apoptosis in thymocytes.

PMID- 9765510
TI  - The aryl hydrocarbon receptor interacts with transcription factor IIB.
AB  - The aryl hydrocarbon receptor (AHR) and its DNA binding partner, the AHR nuclear
      translocator (ARNT), are basic helix-loop-helix transcription factors that
      mediate many of the toxic and carcinogenic effects of polyhalogenated aromatic
      hydrocarbons. The basic regions of the AHR and ARNT contact the GCGTG recognition
      site, whereas both their helix-loop-helix domains and periodicity-ARNT-single
      minded domains participate in heterodimerization. To delineate the transcription
      factors that may facilitate DNA binding and transcriptional activation of the
      AHR/ARNT heterodimer, we questioned whether transcription factor IIB (TFIIB) may
      interact with either the AHR or ARNT and whether this interaction may affect the
      ability of the AHR/ARNT complex to bind DNA. Coaffinity precipitation assays
      demonstrated that both the AHR and ARNT were capable of interacting with TFIIB.
      Domain mapping experiments revealed that TFIIB interacts with the periodicity
      ARNT-single-minded and carboxyl-terminal regions of the AHR. To determine whether
      the interaction between TFIIB and the AHR may affect DNA binding of the AHR and
      ARNT complex, we performed gel shift experiments in the absence and presence of
      TFIIB. The addition of TFIIB significantly increased the formation of the
      AHR/ARNT DNA binding complex, but only if TFIIB was first allowed to interact
      with the AHR before the addition of ARNT. These results indicate that TFIIB
      interacts with the AHR and may stabilize the DNA binding form of the AHR and
      thereby augment the ability of the AHR/ARNT complex to interact with its DNA
      recognition site.

PMID- 9765511
TI  - A synergistic neurotrophic response to l-dihydroxyphenylalanine and nerve growth
      factor.
AB  - The catecholamine precursor l-dihydroxyphenylalanine (L-DOPA) is the primary
      therapeutic intervention for Parkinson's disease. Although short-term exposure
      (30 min) potentiates dopamine (DA) release by elevating quantal size, longer term
      exposure to L-DOPA (48 hr) promotes neurite outgrowth from midbrain DA neurons in
      culture. To characterize long term effects of L-DOPA, we used a pheochromocytoma
      (PC12) line that extends neurites on exposure to nerve growth factor (NGF). L
      DOPA potentiated the outgrowth of processes elicited by NGF. This response did
      not require conversion of L-DOPA to DA, was not caused by agonist effects at DA
      receptors, and was not blocked by the tyrosine kinase inhibitor genistein.
      However, similar results were found after exposure to l-n-acetylcysteine or
      apomorphine, a DA receptor agonist that produces a quinone metabolite, and seemed
      to correlate with glutathione synthesis. Long-term process elaboration was
      blocked by L-buthionine sulfoximine, consistent with mediation by an antioxidant
      mechanism. L-DOPA potentiation of NGF response was important functionally as seen
      by increased quantal neurotransmitter release from the L-DOPA/NGF-treated neurite
      varicosities, which displayed both 2-fold greater quantal size and frequency of
      quantal release. These results demonstrate potentiation by L-DOPA of
      morphological and physiological responses to neurotrophic factors as well as
      synergistic induction of antioxidant pathways. Together with effects on
      transmitter synthesis, these properties seem to provide a basis for the
      compound's long term presynaptic potentiation of DA release and therapeutic
      actions.

PMID- 9765512
TI  - Molecular characterization of human and rat RGS 9L, a novel splice variant
      enriched in dopamine target regions, and chromosomal localization of the RGS 9
      gene.
AB  - A novel splice variant of RGS 9 was isolated from a rat hypothalamus, human
      retina, and a human kidney (Wilm's) tumor. This variant, termed RGS 9L, differs
      from the retinal form (termed RGS 9S) identified previously in that it contains a
      211- (rat) or 205- (human) amino acid proline-rich domain on the carboxyl
      terminus. The pattern of RGS 9 mRNA splicing was tissue specific, with striatum,
      hypothalamus- and nucleus accumbens expressing RGS 9L, whereas retina and pineal
      expressed RGS 9S almost exclusively. This pattern of mRNA splicing seemed to be
      highly conserved between human and rodents, suggesting cell-specific differences
      in the function of these variants. Transient expression of RGS 9L augmented basal
      and beta-adrenergic receptor-stimulated adenylyl cyclase activity while
      suppressing dopamine D2 receptor-mediated inhibition. Furthermore, RGS 9L
      expression greatly accelerated the decay of dopamine D2 receptor-induced GIRK
      current. These results indicate RGS 9L inhibits heterotrimeric Gi function in
      vivo, probably by acting as a GTPase-activating protein. The human RGS 9 gene was
      localized to chromosome 17 q23-24 by radiation hybrid and fluorescent in situ
      hybridization analyses. The RGS 9 gene is within a previously defined locus for
      retinitis pigmentosa (RP 17), a disease that has been linked to genes in the
      rhodopsin/transducin/cGMP signaling pathway.

PMID- 9765513
TI  - HERG and KvLQT1/IsK, the cardiac K+ channels involved in long QT syndromes, are
      targets for calcium channel blockers.
AB  - We examined the effects of the calcium channel blockers nitrendipine, diltiazem,
      verapamil, bepridil, and mibefradil on the cloned HERG and KvLQT1/IsK K+
      channels. These channels generate the rapid and slow components of the cardiac
      delayed rectifier K+ current, and mutations can affect them, which leads to long
      QT syndromes. When expressed in transfected COS cells, HERG is blocked in a
      concentration-dependent manner by bepridil (EC50 = 0.55 microM), verapamil (EC50
      = 0.83 microM), and mibefradil (EC50 = 1.43 microM), whereas nitrendipine and
      diltiazem have negligible effects. Steady state activation and inactivation
      parameters are shifted to more negative values in the presence of the blockers.
      Similarly, KvLQT1/IsK is inhibited by bepridil (EC50 = 10.0 microM) and
      mibefradil (EC50 = 11.8 microM), while being insensitive to nitrendipine,
      diltiazem, or verapamil. These results demonstrate that both cloned K+ channels
      HERG and KvLQT1/IsK, which represent together the cardiac delayed rectifier K+
      current, are sensitive targets to calcium channel blockers. This work may help in
      understanding the mechanisms of action of verapamil in certain ventricular
      tachycardia, as well as some of the deleterious adverse cardiac events associated
      with bepridil.

PMID- 9765514
TI  - Agonist induced homologous desensitization of mu-opioid receptors mediated by G
      protein-coupled receptor kinases is dependent on agonist efficacy.
AB  - Using Xenopus laevis oocytes coexpressing mammalian mu-opioid receptors (MORs),
      beta-adrenergic receptor kinase 2 (beta-ARK2) [also called G protein-coupled
      receptor kinase (GRK3)], and beta-arrestin 2 (beta-arr 2), we compared the rates
      of beta-ARK2 (GRK3)- and beta-arr 2-mediated homologous receptor desensitization
      produced by treatment with opioid agonists of different efficacies. The response
      to MOR activation was measured using two-electrode voltage clamp as an increase
      in the conductance of the coexpressed G protein-coupled inwardly rectifying
      potassium (heteromultimer of KIR3.1 and KIR3.4) channels. Treatment with opioids
      of high efficacy, either [D-Ala2,N-MePhe4,Gly-ol5]-enkephalin, fentanyl, or
      sufentanyl, produced a GRK3- and beta-arr 2-dependent reduction in response in
      <20 min, whereas treatment with the partial agonist morphine produced receptor
      desensitization at a significantly slower rate. Because GRK3 requires activation
      and membrane targeting by free G protein betagamma subunits released after
      agonist-mediated activation of G proteins, a low efficacy agonist such as
      morphine may produce weak receptor desensitization as a consequence of poor GRK3
      activation. To address this hypothesis, we substituted GRK5, a GRK that does not
      require activation by G protein betagamma. In oocytes expressing GRK5 instead of
      GRK3, both [D-Ala2,N-MePhe4, Gly-ol5]enkephalin and fentanyl, but not morphine,
      produced desensitization of MOR-activated potassium conductance. Thus, mu-opioid
      agonists produced significant receptor desensitization, mediated by either GRK3
      or GRK5, at a rate dependent on agonist efficacy.

PMID- 9765515
TI  - A common anticonvulsant binding site for phenytoin, carbamazepine, and
      lamotrigine in neuronal Na+ channels.
AB  - Phenytoin, carbamazepine, and lamotrigine are anticonvulsants frequently
      prescribed in seizure clinics. These drugs all show voltage-dependent inhibition
      of Na+ currents, which has been implicated as the major mechanism underlying the
      antiepileptic effect. In this study, I examine the inhibition of Na+ currents by
      mixtures of different anticonvulsants. Quantitative analysis of the shift of
      steady state inactivation curve in the presence of multiple drugs argues that one
      channel can be occupied by only one drug molecule. Moreover, the recovery from
      inhibition by a mixture of two drugs (a fast-unbinding drug plus a slow-unbinding
      drug) is faster, or at least not slower, than the recovery from inhibition by the
      slow-unbinding drug alone. Such kinetic characteristics further strengthen the
      argument that binding of one anticonvulsant to the Na+ channel precludes binding
      of the other. It also is found that these anticonvulsants are effective
      inhibitors of Na+ currents only when applied externally, not internally.
      Altogether these findings suggest that phenytoin, carbamazepine, and lamotrigine
      bind to a common receptor located on the extracellular side of the Na+ channel.
      Because these anticonvulsants all have much higher affinity to the inactivated
      state than to the resting state of the Na+ channel, the anticonvulsant receptor
      probably does not exist in the resting state. Thus, there may be correlative
      conformational changes for the making of the receptor on the extracellular side
      of the channel during the gating process.

PMID- 9765516
TI  - Detachment of cytochrome c by cationic drugs from membranes containing acidic
      phospholipids: comparison of lidocaine, propranolol, and gentamycin.
AB  - A large number of pharmaceutically active compounds have a high affinity to
      acidic phospholipids; good examples are the cationic compounds lidocaine,
      propranolol, and gentamycin. These drugs influenced the lipid dynamics of
      liposomes composed of phosphatidylcholine and the acidic phosphatidylglycerol, as
      judged by the excimer/monomer emission intensity ratio for a pyrene-labeled
      phospholipid analog, as well as by polarization of DPH fluorescence. When the
      mole fraction X of PG (XPG) was 0.20, lidocaine increased membrane fluidity. The
      opposite was true for propranolol, which caused the formation of pyrene lipid
      enriched microdomains. Gentamycin had no apparent effect. At XPG = 1.00, all
      these drugs rigidified membrane. Subsequently, we investigated the detachment of
      a cationic peripheral membrane protein, cytochrome c (cyt c), by these compounds
      from liposomes. This was accomplished by monitoring resonance energy transfer
      from a pyrene-labeled phospholipid to the heme of cyt c. The efficiency of the
      above compounds to dissociate cyt c varied considerably. In brief, significantly
      lower concentrations of gentamycin than propranolol or lidocaine were required
      for half-maximal dissociation of cyt c from liposomes, although the final extent
      of protein detachment by gentamycin was less complete. ATP augmented the
      dissociation of cyt c from membranes by lidocaine and propranolol. Stopped-flow
      measurements also revealed that the half-times differed for the release of cyt c
      from the membranes. Our results are likely to reflect differences in the
      contributions of the electrostatic interactions and hydrophobicity to the
      drug/lipid interaction and comply with two different acidic phospholipid binding
      sites in cyt c.

PMID- 9765517
TI  - Lysine point mutations in Na+ channel D4-S6 reduce inactivated channel block by
      local anesthetics.
AB  - Voltage-gated Na+ channels are a primary target for local anesthetics (LAs). Open
      or inactivated Na+ channels usually have a severalfold higher affinity for LAs
      than do resting channels. Hille's modulated receptor hypothesis attributed the
      changes in LA affinity to state-dependent alterations in the conformation of the
      LA receptor. We expressed wild-type and mutant rat skeletal muscle (mu1) Na+
      channels in human embryonic kidney cells to investigate the state-dependent
      modulation of LA receptor affinity. As an alternative approach to using alanine
      for point mutation, we substituted lysine (a hydrophilic residue) for native
      residues in the putative LA receptor located in D4-S6 of the mu1 Na+ channel.
      Lysine mutation at Y1586 did not alter resting channel affinity for cocaine but
      did reduce resting affinity at F1579K and N1584K by 2- and 3-fold, respectively.
      Compared with mu1, resting benzocaine block did not change at F1579K, decreased
      at N1584K, and increased at Y1586K. These effects on resting block could largely
      be accounted for by either steric/charge interference or cation-pi electron
      interactions between particular moieties on the LA and lysine. Surprisingly,
      lysine substitution at these residues allowed the channels to undergo steady
      state fast inactivation yet reduced inactivated channel block by cocaine by up to
      27-fold and reduced the benzocaine-induced leftward shift in the h(infinity)
      curve by up to 22 mV. Our data suggest that transitions in channel state indeed
      invoke conformational changes in the LA receptor and that lysine mutations in the
      LA receptor region alter such conformational changes during the transition to the
      inactivated state.

PMID- 9765519
TI  - Cell wall loosening by expansins.

PMID- 9765518
TI  - Regulation of rabbit cytochrome P450 2E1 expression in HepG2 cells by insulin and
      thyroid hormone.
AB  - The regulation of cytochrome P450 (CYP) 2E1, the ethanol-inducible isoform, is
      particularly complex. The level is affected by a variety of other foreign
      compounds, by insulin (as studied in several laboratories), and by
      triiodothyronine (T3), which has not been previously examined at the molecular
      level. In the present investigation, a stably transfected HepG2 cell line
      harboring a rabbit CYP2E1 minigene containing the coding sequence together with
      1.6 kilobases of the 5' flanking region and the untranslated region (UTR), as
      well as 0.5 kilobases of the 3' UTR, was established. Western blot analysis
      showed that 1 microM insulin decreased the CYP2E1 protein level in a dose- and
      time-dependent manner, whereas 1 microM T3 increased the level 2-fold in 1 day
      and 8-fold in 5 days. Similarly, steady state CYP2E1 mRNA levels were decreased
      by insulin but were increased by T3. Neither hormone affected the transcription
      rate of the CYP2E1 5' flanking region with an UTR/luciferase fusion gene,
      indicating that the regulation is post-transcriptional in this system under our
      experimental conditions. When the CYP2E1 3' UTR was removed from the minigene,
      CYP2E1 mRNA and protein were up-regulated by insulin but were not affected by T3.
      These findings, including mRNA half-life determinations, indicate that the
      effects of insulin and T3 are a result of altered mRNA stability and that the 3'
      UTR of CYP2E1 contains regulatory information for these hormone-mediated effects.

PMID- 9765520
TI  - How does auxin turn on genes?

PMID- 9765521
TI  - Shifts of intracellular pH distribution as a part of the signal mechanism leading
      to the elicitation of benzophenanthridine alkaloids . Phytoalexin biosynthesis in
      cultured cells of eschscholtzia californica 
AB  - Cultured cells of Eschscholtzia californica (Californian poppy) respond to a
      yeast elicitor preparation or Penicillium cyclopium spores with the production of
      benzophenanthridine alkaloids, which are potent phytoalexins. Confocal pH mapping
      with the probe carboxy-seminaphthorhodafluor-1-acetoxymethylester revealed
      characteristic shifts of the pH distribution in challenged cells: within a few
      minutes after elicitor contact a transient acidification of cytoplasmic and
      nuclear areas occurred in parallel with an increase of the vacuolar pH. The
      change of proton concentration in the vacuole and in the extravacuolar area
      showed a nearly constant relation, indicating an efflux of vacuolar protons into
      the cytosol. A 10-min treatment with 2 mM butyric or pivalic acid caused a
      transient acidification of the cytoplasm comparable to that observed after
      elicitor contact and also induced alkaloid biosynthesis. Experimental depletion
      of the vacuolar proton pool reversibly prevented both the elicitor-triggered pH
      shifts and the induction of alkaloid biosynthesis. pH shifts and induction of
      alkaloid biosynthesis showed a similar dependence on the elicitor concentration.
      Net efflux of K+, alkalinization of the outer medium, and browning of the cells
      were evoked only at higher elicitor concentrations. We suggest that transient
      acidification of the cytoplasm via efflux of vacuolar protons is both a necessary
      and sufficient step in the signal path toward biosynthesis of benzophenanthridine
      alkaloids in Californian poppy cells.

PMID- 9765522
TI  - Eucalypt MADS-box genes expressed in developing flowers.
AB  - Three MADS-box genes were identified from a cDNA library derived from young
      flowers of Eucalyptus grandis W. Hill ex Maiden. The three egm genes are single
      copy genes and are expressed almost exclusively in flowers. The egm1 and egm3
      genes shared strongest homology with other plant MADS-box genes, which mediate
      between the floral meristem and the organ-identity genes. The egm3 gene was also
      expressed strongly in the receptacle or floral tube, which surrounds the carpels
      in the eucalypt flower and bears the sepals, petals, and numerous stamens. There
      appeared to be a group of genes in eucalypts with strong homology with the 3'
      region of the egm1 gene. The egm2 gene was expressed in eucalypt petals and
      stamens and was most homologous to MADS-box genes, which belong to the globosa
      group of genes, which regulate organogenesis of the second and third floral
      whorls. The possible role of these three genes in eucalypt floral development is
      discussed.

PMID- 9765523
TI  - Developmental regulation of intercellular protein trafficking through
      plasmodesmata in tobacco leaf epidermis 
AB  - Plasmodesmata mediate direct cell-to-cell communication in plants. One of their
      significant features is that primary plasmodesmata formed at the time of
      cytokinesis often undergo structural modifications, by the de novo addition of
      cytoplasmic strands across cell walls, to become complex secondary plasmodesmata
      during plant development. Whether such modifications allow plasmodesmata to gain
      special transport functions has been an outstanding issue in plant biology. Here
      we present data showing that the cucumber mosaic virus 3a movement protein
      (MP):green fluorescent protein (GFP) fusion was not targeted to primary
      plasmodesmata in the epidermis of young or mature leaves in transgenic tobacco
      (Nicotiana tabacum) plants constitutively expressing the 3a:GFP fusion gene.
      Furthermore, the cucumber mosaic virus 3a MP:GFP fusion protein produced in
      planta by biolistic bombardment of the 3a:GFP fusion gene did not traffic between
      cells interconnected by primary plasmodesmata in the epidermis of a young leaf.
      In contrast, the 3a MP:GFP was targeted to complex secondary plasmodesmata and
      trafficked from cell to cell when a leaf reached a certain developmental stage.
      These data provide the first experimental evidence, to our knowledge, that
      primary and complex secondary plasmodesmata have different protein-trafficking
      functions and suggest that complex secondary plasmodesmata may be formed to
      traffic specific macromolecules that are important for certain stages of leaf
      development.

PMID- 9765524
TI  - Metallothioneins 1 and 2 have distinct but overlapping expression patterns in
      Arabidopsis.
AB  - The spatial and temporal expression patterns of metallothionein (MT) isoforms
      MT1a and MT2a were investigated in vegetative and reproductive tissues of
      untreated and copper-treated Arabidopsis by in situ hybridization and by northern
      blotting. In control plants, MT1a mRNA was localized in leaf trichomes and in the
      vascular tissue in leaves, roots, flowers, and germinating embryos. In copper
      treated plants, MT1a expression was also observed in the leaf mesophyll and in
      vascular tissue of developing siliques and seeds. In contrast, MT2a was expressed
      primarily in the trichomes of both untreated and copper-treated plants. In copper
      treated plants, MT2a mRNA was also expressed in siliques. Northern-hybridization
      studies performed on developing seedlings and leaves showed temporal variations
      of MT1a gene expression but not of MT2a expression. The possible implications of
      these findings for the cellular roles of MTs in plants are discussed.

PMID- 9765525
TI  - A fiberless seed mutation in cotton is associated with lack of fiber cell
      initiation in ovule epidermis and alterations in sucrose synthase expression and
      carbon partitioning in developing seeds 
AB  - Fiber cell initiation in the epidermal cells of cotton (Gossypium hirsutum L.)
      ovules represents a unique example of trichome development in higher plants.
      Little is known about the molecular and metabolic mechanisms controlling this
      process. Here we report a comparative analysis of a fiberless seed (fls) mutant
      (lacking fibers) and a normal (FLS) mutant to better understand the initial
      cytological events in fiber development and to analyze the metabolic changes that
      are associated with the loss of a major sink for sucrose during cellulose
      biosynthesis in the mutant seeds. On the day of anthesis (0 DAA), the mutant
      ovular epidermal cells lacked the typical bud-like projections that are seen in
      FLS ovules and are required for commitment to the fiber development pathway. Cell
      specific gene expression analyses at 0 DAA showed that sucrose synthase (SuSy)
      RNA and protein were undetectable in fls ovules but were in abundant, steady
      state levels in initiating fiber cells of the FLS ovules. Tissue-level analyses
      of developing seeds 15 to 35 DAA revealed an altered temporal pattern of SuSy
      expression in the mutant relative to the normal genotype. Whether the altered
      programming of SuSy expression is the cause or the result of the mutation is
      unknown. The developing seeds of the fls mutant have also shown several
      correlated changes that represent altered carbon partitioning in seed coats and
      cotyledons as compared with the FLS genotype.

PMID- 9765526
TI  - Arabidopsis Rho-related GTPases: differential gene expression in pollen and polar
      localization in fission yeast.
AB  - The Rho small GTP-binding proteins are versatile, conserved molecular switches in
      eukaryotic signal transduction. Plants contain a unique subfamily of Rho-GTPases
      called Rop (Rho-related GTPases from plants). Our previous studies involving
      injection of antibodies indicated that the pea Rop GTPase Rop1Ps is critical for
      pollen tube growth. In this study we show that overexpression of an apparent
      Arabidopsis ortholog of Rop1Ps, Rop1At, induces isotropic cell growth in fission
      yeast (Schizosaccharomyces pombe) and that green fluorescence protein-tagged
      Rop1At displays polar localization to the site of growth in yeast. We found that
      Rop1At and two other Arabidopsis Rops, Rop3At and Rop5At, are all expressed in
      mature pollen. All three pollen Rops fall into the same subgroup as Rop1Ps and
      diverge from those Rops that are not expressed in mature pollen, suggesting a
      coupling of the structural conservation of Rop GTPases to their gene expression
      in pollen. However, pollen-specific transcript accumulation for Rop1At is much
      higher than that for Rop3At and Rop5At. Furthermore, Rop1At is specifically
      expressed in anthers, whereas Rop3At and Rop5At are also expressed in vegetative
      tissues. In transgenic plants containing the Rop1At promoter:GUS fusion gene, GUS
      is specifically expressed in mature pollen and pollen tubes. We propose that
      Rop1At may play a predominant role in the regulation of polarized cell growth in
      pollen, whereas its close relatives Rop3At and Rop5At may be functionally
      redundant to Rop1At in pollen.

PMID- 9765527
TI  - Proteasome inhibitors prevent tracheary element differentiation in zinnia
      mesophyll cell cultures 
AB  - To determine whether proteasome activity is required for tracheary element (TE)
      differentiation, the proteasome inhibitors clasto-lactacystin beta-lactone and
      carbobenzoxy-leucinyl-leucinyl-leucinal (LLL) were used in a zinnia (Zinnia
      elegans) mesophyll cell culture system. The addition of proteasome inhibitors at
      the time of culture initiation prevented differentiation otherwise detectable at
      96 h. Inhibition of the proteasome at 48 h, after cellular commitment to
      differentiation, did not alter the final percentage of TEs compared with
      controls. However, proteasome inhibition at 48 h delayed the differentiation
      process by approximately 24 h, as indicated by examination of both morphological
      markers and the expression of putative autolytic proteases. These results
      indicate that proteasome function is required both for induction of TE
      differentiation and for progression of the TE program in committed cells.
      Treatment at 48 h with LLL but not clasto-lactacystin beta-lactone resulted in
      partial uncoupling of autolysis from differentiation. Results from gel analysis
      of protease activity suggested that the observed incomplete autolysis was due to
      the ability of LLL to inhibit TE cysteine proteases.

PMID- 9765528
TI  - S-adenosyl-L-methionine:L-methionine S-methyltransferase from germinating barley.
      Purification and localization.
AB  - S-Adenosyl-L-methionine:L-methionine S-methyltransferase (MMT) catalyzes the
      synthesis of S-methyl-L-methionine (SMM) from L-methionine and S-adenosyl-L
      methionine. SMM content increases during barley (Hordeum vulgare L.) germination.
      Elucidating the role of this compound is important from both a fundamental and a
      technological standpoint, because SMM is the precursor of dimethylsulfide, a
      biogenic source of atmospheric S and an undesired component in beer. We present a
      simple purification scheme for the MMT from barley consisting of 10% to 25%
      polyethylene glycol fractionation, anion-exchange chromatography on
      diethylaminoethyl-Sepharose, and affinity chromatography on adenosine-agarose. A
      final activity yield of 23% and a 2765-fold purification factor were obtained.
      After digestion of the protein with protease, the amino acid sequence of a major
      peptide was determined and used to produce a synthetic peptide. A polyclonal
      antibody was raised against this synthetic peptide conjugated to activated
      keyhole limpet hemocyanin. The antibody recognized the 115-kD denatured MMT
      protein and native MMT. During barley germination, both the specific activity and
      the amount of MMT protein increased. MMT-specific activity was found to be higher
      in the root and shoot than in the endosperm. MMT could be localized by an
      immunohistochemical approach in the shoot, scutellum, and aleurone cells but not
      in the root or endosperm (including aleurone).

PMID- 9765529
TI  - Photosynthetic and heterotrophic ferredoxin isoproteins are colocalized in fruit
      plastids of tomato 
AB  - Fruit tissues of tomato (Lycopersicon esculentum Mill.) contain both
      photosynthetic and heterotrophic ferredoxin (FdA and FdE, respectively)
      isoproteins, irrespective of their photosynthetic competence, but we did not
      previously determine whether these proteins were colocalized in the same
      plastids. In isolated fruit chloroplasts and chromoplasts, both FdA and FdE were
      detected by immunoblotting. Colocalization of FdA and FdE in the same plastids
      was demonstrated using double-staining immunofluorescence microscopy. We also
      found that FdA and FdE were colocalized in fruit chloroplasts and
      chloroamyloplasts irrespective of sink status of the plastid. Immunoelectron
      microscopy demonstrated that FdA and FdE were randomly distributed within the
      plastid stroma. To investigate the significance of the heterotrophic Fd in fruit
      plastids, Glucose 6-phosphate dehydrogenase (G6PDH) activity was measured in
      isolated fruit and leaf plastids. Fruit chloroplasts and chromoplasts showed much
      higher G6PDH activity than did leaf chloroplasts, suggesting that high G6PDH
      activity is linked with FdE to maintain nonphotosynthetic production of reducing
      power. This result suggested that, despite their morphological resemblance, fruit
      chloroplasts are functionally different from their leaf counterparts.

PMID- 9765530
TI  - Characterization of a granule-bound starch synthase isoform found in the pericarp
      of wheat.
AB  - Waxy wheat (Triticum aestivum L.) lacks the waxy protein, which is also known as
      granule-bound starch synthase I (GBSSI). The starch granules of waxy wheat
      endosperm and pollen do not contain amylose and therefore stain red-brown with
      iodine. However, we observed that starch from pericarp tissue of waxy wheat
      stained blue-black and contained amylose. Significantly higher starch synthase
      activity was detected in pericarp starch granules than in endosperm starch
      granules. A granule-bound protein that differed from GBSSI in molecular mass and
      isoelectric point was detected in the pericarp starch granules but not in
      granules from endosperm. This protein was designated GBSSII. The N-terminal amino
      acid sequence of GBSSII, although not identical to wheat GBSSI, showed strong
      homology to waxy proteins or GBSSIs of cereals and potato, and contained the
      motif KTGGL, which is the putative substrate-binding site of GBSSI of plants and
      of glycogen synthase of Escherichia coli. GBSSII cross-reacted specifically with
      antisera raised against potato and maize GBSSI. This study indicates that GBSSI
      and GBSSII are expressed in a tissue-specific manner in different organs, with
      GBSSII having an important function in amylose synthesis in the pericarp.

PMID- 9765531
TI  - Overexpression of an Arabidopsis cDNA encoding a sterol-C24(1)-methyltransferase
      in tobacco modifies the ratio of 24-methyl cholesterol to sitosterol and is
      associated with growth reduction.
AB  - Higher plants synthesize 24-methyl sterols and 24-ethyl sterols in defined
      proportions. As a first step in investigating the physiological function of this
      balance, an Arabidopsis cDNA encoding an S-adenosyl-L-methionine 24-methylene
      lophenol-C24(1)-methyltransferase, the typical plant enzyme responsible for the
      production of 24-ethyl sterols, was expressed in tobacco (Nicotiana tabacum L.)
      under the control of a constitutive promoter. Transgenic plants displayed a novel
      24-alkyl-Delta5-sterol profile: the ratio of 24-methyl cholesterol to sitosterol,
      which is close to 1 in the wild type, decreased dramatically to values ranging
      from 0.01 to 0.31. In succeeding generations of transgenic tobacco, a high S
      adenosyl-L-methionine 24-methylene lophenol-C24(1)-methyltransferase enzyme
      activity and, consequently, a low ratio of 24-methyl cholesterol to sitosterol,
      was associated with reduced growth compared with the wild type. However, this new
      morphological phenotype appeared only below the threshold ratio of 24-methyl
      cholesterol to sitosterol of approximately 0.1. Because the size of cells was
      unchanged in small, transgenic plants, we hypothesize that a radical decrease of
      24-methyl cholesterol and/or a concomitant increase of sitosterol would be
      responsible for a change in cell division through as-yet unknown mechanisms.

PMID- 9765532
TI  - Manipulation of glutathione and amino acid biosynthesis in the chloroplast 
AB  - Poplars (Populus tremula x Populus alba) were transformed to overexpress
      Escherichia coli gamma-glutamylcysteine synthetase (gamma-ECS) or glutathione
      synthetase in the chloroplast. Five independent lines of each transformant
      strongly expressed the introduced gene and possessed markedly enhanced activity
      of the gene product. Glutathione (GSH) contents were unaffected by high
      chloroplastic glutathione synthetase activity. Enhanced chloroplastic gamma-ECS
      activity markedly increased gamma-glutamylcysteine and GSH levels. These effects
      are similar to those previously observed in poplars overexpressing these enzymes
      in the cytosol. Similar to cytosolic gamma-ECS overexpression, chloroplastic
      overexpression did not deplete foliar cysteine or methionine pools and did not
      lead to morphological changes. Light was required for maximal accumulation of GSH
      in poplars overexpressing gamma-ECS in the chloroplast. High chloroplastic, but
      not cytosolic, gamma-ECS activities were accompanied by increases in amino acids
      synthesized in the chloroplast. We conclude that (a) GSH synthesis can occur in
      the chloroplast and the cytosol and may be up-regulated in both compartments by
      increased gamma-ECS activity, (b) interactions between GSH synthesis and the
      pathways supplying the necessary substrates are similar in both compartments, and
      (c) chloroplastic up-regulation of GSH synthesis is associated with an activating
      effect on the synthesis of specific amino acids formed in the chloroplast.

PMID- 9765534
TI  - Light and excess manganese . Implications for oxidative stress in common bean 
AB  - The effect of light intensity on antioxidants, antioxidant enzymes, and
      chlorophyll content was studied in common bean (Phaseolus vulgaris L.) exposed to
      excess Mn. Leaves of bean genotypes contrasting in Mn tolerance were exposed to
      two different light intensities and to excess Mn; light was controlled by shading
      a leaflet with filter paper. After 5 d of Mn treatment ascorbate was depleted by
      45% in leaves of the Mn-sensitive genotype ZPV-292 and by 20% in the Mn-tolerant
      genotype CALIMA. Nonprotein sulfhydryl groups and glutathione reductase were not
      affected by Mn or light treatment. Ten days of Mn-toxicity stress increased leaf
      ascorbate peroxidase activity of cv ZPV-292 by 78% in low light and by 235% in
      high light, and superoxide dismutase activity followed a similar trend. Increases
      of ascorbate peroxidase and superoxide dismutase activity observed in cv CALIMA
      were lower than those observed in the susceptible cv ZPV-292. The cv CALIMA had
      less ascorbate oxidation under excess Mn-toxicity stress. Depletion of ascorbate
      occurred before the onset of chlorosis in Mn-stressed plants, especially in cv
      ZPV-292. Lipid peroxidation was not detected in floating leaf discs of mature
      leaves exposed to excess Mn. Our results suggest that Mn toxicity may be mediated
      by oxidative stress, and that the tolerant genotype may maintain higher ascorbate
      levels under stress than the sensitive genotype.

PMID- 9765533
TI  - Inhibition of the gravitropic response of snapdragon spikes by the calcium
      channel blocker lanthanum chloride.
AB  - The putative Ca(2+)-channel blocker LaCl3 prevented the gravitropic bending of
      cut snapdragon (Antirrhinum majus L.) spikes (S. Philosoph-Hadas, S. Meir, I.
      Rosenberger, A.H. Halevy [1996] Plant Physiol 110: 301-310) and inhibited stem
      curvature to a greater extent than vertical and horizontal stem elongation at the
      bending zone. This might indicate that LaCl3, which modulates cytosolic Ca2+,
      does not influence general stem-growth processes but may specifically affect
      other gravity-associated processes occurring at the stem-bending zone. Two such
      specific gravity-dependent events were found to occur in the bending zone of
      snapdragon spikes: sedimentation of starch-containing chloroplasts at the bottom
      of stem cortex cells, as seen in cross-sections, and establishment of an ethylene
      gradient across the stem. Our results show that the lateral sedimentation of
      chloroplasts associated with gravity sensing was prevented in cross-sections
      taken from the bending zone of LaCl3-treated and subsequently gravistimulated
      spikes and that LaCl3 completely prevented the gravity-induced, asymmetric
      ethylene production established across the stem-bending zone. These data indicate
      that LaCl3 inhibits stem curvature of snapdragon spikes by preventing several
      gravity-dependent processes. Therefore, we propose that the gravitropic response
      of shoots could be mediated through a Ca(2+)-dependent pathway involving
      modulation of cytosolic Ca2+ at various stages.

PMID- 9765535
TI  - Computation of surface electrical potentials of plant cell membranes .
      Correspondence To published zeta potentials from diverse plant sources 
AB  - A Gouy-Chapman-Stern model has been developed for the computation of surface
      electrical potential (psi0) of plant cell membranes in response to ionic solutes.
      The present model is a modification of an earlier version developed to compute
      the sorption of ions by wheat (Triticum aestivum L. cv Scout 66) root plasma
      membranes. A single set of model parameters generates values for psi0 that
      correlate highly with published zeta potentials of protoplasts and plasma
      membrane vesicles from diverse plant sources. The model assumes ion binding to a
      negatively charged site (R- = 0.3074 &mgr;mol m-2) and to a neutral site (P0 =
      2.4 &mgr;mol m-2) according to the reactions R- + IZ &rlharr; RIZ-1 and P0 + IZ
      &rlharr; PIZ, where IZ represents an ion of charge Z. Binding constants for the
      negative site are 21, 500 M-1 for H+, 20,000 M-1 for Al3+, 2,200 M-1 for La3+, 30
      M-1 for Ca2+ and Mg2+, and 1 M-1 for Na+ and K+. Binding constants for the
      neutral site are 1/180 the value for binding to the negative site. Ion activities
      at the membrane surface, computed on the basis of psi0, appear to determine many
      aspects of plant-mineral interactions, including mineral nutrition and the
      induction and alleviation of mineral toxicities, according to previous and
      ongoing studies. A computer program with instructions for the computation of
      psi0, ion binding, ion concentrations, and ion activities at membrane surfaces
      may be requested from the authors.

PMID- 9765536
TI  - Three mechanisms for the calcium alleviation of mineral toxicities 
AB  - Ca2+ in rooting medium is essential for root elongation, even in the absence of
      added toxicants. In the presence of rhizotoxic levels of Al3+, H+, or Na+ (or
      other cationic toxicants), supplementation of the medium with higher levels of
      Ca2+ alleviates growth inhibition. Experiments to determine the mechanisms of
      alleviation entailed measurements of root elongation in wheat (Triticum aestivum
      L. cv Scout 66) seedlings in controlled medium. A Gouy-Chapman-Stern model was
      used to compute the electrical potentials and the activities of ions at the root
      cell plasma membrane surfaces. Analysis of root elongation relative to the
      computed surface activities of ions revealed three separate mechanisms of Ca2+
      alleviation. Mechanism I is the displacement of cell-surface toxicant by the Ca2+
      induced reduction in cell-surface negativity. Mechanism II is the restoration of
      Ca2+ at the cell surface if the surface Ca2+ has been reduced by the toxicant to
      growth-limiting levels. Mechanism III is the collective ameliorative effect of
      Ca2+ beyond mechanisms I and II, and may involve Ca2+-toxicant interactions at
      the cell surface other than the displacement interactions of mechanisms I and II.
      Mechanism I operated in the alleviation of all of the tested toxicities;
      mechanism II was generally a minor component of alleviation; and mechanism III
      was toxicant specific and operated strongly in the alleviation of Na+ toxicity,
      moderately in the alleviation of H+ toxicity, and not at all in the alleviation
      of Al3+ toxicity.

PMID- 9765537
TI  - Changes in growth CO2 result in rapid adjustments of ribulose-1, 5-bisphosphate
      Carboxylase/Oxygenase small subunit gene expression in expanding and mature
      leaves of rice 
AB  - The accumulation of soluble carbohydrates resulting from growth under elevated
      CO2 may potentially signal the repression of gene activity for the small subunit
      of ribulose-1,5-bisphosphate carboxylase/oxygenase (rbcS). To test this
      hypothesis we grew rice (Oryza sativa L.) under ambient (350 &mgr;L L-1) and high
      (700 &mgr;L L-1) CO2 in outdoor, sunlit, environment-controlled chambers and
      performed a cross-switching of growth CO2 concentration at the late-vegetative
      phase. Within 24 h, plants switched to high CO2 showed a 15% and 23% decrease in
      rbcS mRNA, whereas plants switched to ambient CO2 increased 27% and 11% in
      expanding and mature leaves, respectively. Ribulose-1,5-bisphosphate
      carboxylase/oxygenase total activity and protein content 8 d after the switch
      increased up to 27% and 20%, respectively, in plants switched to ambient CO2, but
      changed very little in plants switched to high CO2. Plants maintained at high CO2
      showed greater carbohydrate pool sizes and lower rbcS transcript levels than
      plants kept at ambient CO2. However, after switching growth CO2 concentration,
      there was not a simple correlation between carbohydrate and rbcS transcript
      levels. We conclude that although carbohydrates may be important in the
      regulation of rbcS expression, changes in total pool size alone could not predict
      the rapid changes in expression that we observed.

PMID- 9765538
TI  - Influence of water content and temperature on molecular mobility and
      intracellular glasses in seeds and pollen 
AB  - Although the occurrence of intracellular glasses in seeds and pollen has been
      established, physical properties such as rotational correlation times and
      viscosity have not been studied extensively. Using electron paramagnetic
      resonance spectroscopy, we examined changes in the molecular mobility of the
      hydrophilic nitroxide spin probe 3-carboxy-proxyl during melting of intracellular
      glasses in axes of pea (Pisum sativum L.) seeds and cattail (Typha latifolia L. )
      pollen. The rotational correlation time of the spin probe in intracellular
      glasses of both organisms was approximately 10(-3) s. Using the distance between
      the outer extrema of the electron paramagnetic resonance spectrum (2Azz) as a
      measure of molecular mobility, we found a sharp increase in mobility at a
      definite temperature during heating. This temperature increased with decreasing
      water content of the samples. Differential scanning calorimetry data on these
      samples indicated that this sharp increase corresponded to melting of the glassy
      matrix. Molecular mobility was found to be inversely correlated with storage
      stability. With decreasing water content, the molecular mobility reached a
      minimum, and increased again at very low water content. Minimum mobility and
      maximum storage stability occurred at a similar water content. This correlation
      suggests that storage stability might be at least partially controlled by
      molecular mobility. At low temperatures, when storage longevity cannot be
      determined on a realistic time scale, 2Azz measurements can provide an estimate
      of the optimum storage conditions.

PMID- 9765539
TI  - Natural genetic transformation by agrobacterium rhizogenes . Annual flowering in
      two biennials, belgian endive and carrot 
AB  - Genetic transformation of Belgian endive (Cichorium intybus) and carrot (Daucus
      carota) by Agrobacterium rhizogenes resulted in a transformed phenotype,
      including annual flowering. Back-crossing of transformed (R1) endive plants
      produced a line that retained annual flowering in the absence of the other traits
      associated with A. rhizogenes transformation. Annualism was correlated with the
      segregation of a truncated transferred DNA (T-DNA) insertion. During vegetative
      growth, carbohydrate reserves accumulated normally in these annuals, and they
      were properly mobilized prior to anthesis. The effects of individual root
      inducing left-hand T-DNA genes on flowering were tested in carrot, in which rolC
      (root locus) was the primary promoter of annualism and rolD caused extreme
      dwarfism. We discuss the possible adaptive significance of this attenuation of
      the phenotypic effects of root-inducing left-hand T-DNA.

PMID- 9765540
TI  - A phosphothreonine residue at the C-terminal end of the plasma membrane H+-ATPase
      is protected by fusicoccin-induced 14-3-3 binding.
AB  - We have isolated the plasma membrane H+-ATPase in a phosphorylated form from
      spinach (Spinacia oleracea L.) leaf tissue incubated with fusicoccin, a fungal
      toxin that induces irreversible binding of 14-3-3 protein to the C terminus of
      the H+-ATPase, thus activating H+ pumping. We have identified threonine-948, the
      second residue from the C-terminal end of the H+-ATPase, as the phosphorylated
      amino acid. Turnover of the phosphate group of phosphothreonine-948 was inhibited
      by 14-3-3 binding, suggesting that this residue may form part of a binding motif
      for 14-3-3. This is the first identification to our knowledge of an in vivo
      phosphorylation site in the plant plasma membrane H+-ATPase.

PMID- 9765541
TI  - Evidence that auxin-induced growth of tobacco leaf tissues does not involve cell
      wall acidification 
AB  - Interveinal strips (10 x 1.5 mm) excised from growing tobacco (Nicotiana tabacum
      L. cv Xanthi) leaves have an auxin-specific, epinastic growth response that is
      developmentally regulated and is not the result of ethylene induction (C.P.
      Keller, E. Van Volkenburgh [1997] Plant Physiol 113: 603-610). We report here
      that auxin (10 &mgr;M naphthalene acetic acid) treatment of strips does not
      result in plasma membrane hyperpolarization or detectable proton efflux. This
      result is in contrast to the expected responses elicited by 1 &mgr;M fusicoccin
      (FC) treatment, which in other systems mimics auxin growth promotion through
      stimulation of the plasma membrane H+-ATPase and resultant acid wall loosening;
      FC produced both hyperpolarization and proton efflux in leaf strips. FC-induced
      growth was much more inhibited by a strong neutral buffer than was auxin-induced
      growth. Measurements of the osmotic concentration of strips suggested that
      osmotic adjustment plays no role in the auxin-induced growth response. Although
      cell wall loosening of some form appears to be involved, taken together, our
      results suggest that auxin-induced growth stimulation of tobacco leaf strips
      results primarily from a mechanism not involving acid growth.

PMID- 9765542
TI  - Intermediates of salicylic acid biosynthesis in tobacco 
AB  - Salicylic acid (SA) is an important component of systemic-acquired resistance in
      plants. It is synthesized from benzoic acid (BA) as part of the phenylpropanoid
      pathway. Benzaldehyde (BD), a potential intermediate of this pathway, was found
      in healthy and tobacco mosaic virus (TMV)-inoculated tobacco (Nicotiana tabacum
      L. cv Xanthi-nc) leaf tissue at 100 ng/g fresh weight concentrations as measured
      by gas chromatography-mass spectrometry. BD was also emitted as a volatile
      organic compound from tobacco tissues. Application of gaseous BD to plants
      enclosed in jars caused a 13-fold increase in SA concentration, induced the
      accumulation of the pathogenesis-related transcript PR-1, and increased the
      resistance of tobacco to TMV inoculation. [13C6]BD and [2H5]benzyl alcohol were
      converted to BA and SA. Labeling experiments using [13C1]Phe in temperature
      shifted plants inoculated with the TMV showed high enrichment of cinnamic acids
      (72%), BA (34%), and SA (55%). The endogenous BD, however, contained
      nondetectable enrichment, suggesting that BD was not the intermediate between
      cinnamic acid and BA. These results show that BD and benzyl alcohol promote SA
      accumulation and expression of defense responses in tobacco, and provide insight
      into the early steps of SA biosynthesis.

PMID- 9765543
TI  - Does a low nitrogen supply necessarily lead to acclimation of photosynthesis to
      elevated CO2? 
AB  - Long-term exposure of plants to elevated partial pressures of CO2 (pCO2) often
      depresses photosynthetic capacity. The mechanistic basis for this photosynthetic
      acclimation may involve accumulation of carbohydrate and may be promoted by
      nutrient limitation. However, our current knowledge is inadequate for making
      reliable predictions concerning the onset and extent of acclimation. Many studies
      have sought to investigate the effects of N supply but the methodologies used
      generally do not allow separation of the direct effects of limited N availability
      from those caused by a N dilution effect due to accelerated growth at elevated
      pCO2. To dissociate these interactions, wheat (Triticum aestivum L.) was grown
      hydroponically and N was added in direct proportion to plant growth.
      Photosynthesis did not acclimate to elevated pCO2 even when growth was restricted
      by a low-N relative addition rate. Ribulose-1, 5-bisphosphate
      carboxylase/oxygenase activity and quantity were maintained, there was no
      evidence for triose phosphate limitation of photosynthesis, and tissue N content
      remained within the range recorded for healthy wheat plants. In contrast, wheat
      grown in sand culture with N supplied at a fixed concentration suffered
      photosynthetic acclimation at elevated pCO2 in a low-N treatment. This was
      accompanied by a significant reduction in the quantity of active ribulose-1, 5
      bisphosphate carboxylase/oxygenase and leaf N content.

PMID- 9765544
TI  - Characterization of starch-debranching enzymes in pea embryos 
AB  - Two distinct types of debranching enzymes have been identified in developing pea
      (Pisum sativum L.) embryos using native gel analysis and tests of substrate
      preference on purified or partially purified activities. An isoamylase-like
      activity capable of hydrolyzing amylopectin and glycogen but not pullulan is
      present throughout development and is largely or entirely confined to the
      plastid. Activities capable of hydrolyzing pullulan are present both inside and
      outside of the plastid, and extraplastidial activity increases relative to the
      plastidial activity during development. Both types of debranching enzyme are also
      present in germinating embryos. We argue that debranching enzymes are likely to
      have a role in starch metabolism in the plastid of the developing embryo and in
      starch degradation during germination.

PMID- 9765545
TI  - Characterization of transgenic tobacco with an increased alpha-linolenic acid
      level 
AB  - Microsomal omega-3 fatty acid desaturase catalyzes the conversion of 18:2
      (linoleic acid) to 18:3 (alpha-linolenic acid) in phospholipids, which are the
      main constituents of extrachloroplast membranes. Transgenic tobacco (Nicotiana
      tabacum) plants with increased 18:3 contents (designated SIIn plants) were
      produced through the introduction of a construct with the tobacco microsomal
      omega-3 fatty acid desaturase gene under the control of the highly efficient
      promoter containing the E12Omega sequence. 18:3 contents in the SIIn plants were
      increased by about 40% in roots and by about 10% in leaves compared with the
      control plants. With regard to growth at 15 degreesC and 25 degreesC and the
      ability to tolerate chilling at 1 degreesC and 5 degreesC, there were no
      discernible differences between the SIIn and the control plants. Freezing
      tolerance in leaves and roots, which was assessed by electrolyte leakage, was
      almost the same between the SIIn and the control plants. The fluidity of plasma
      membrane from the SIIn plants was almost the same as that of the control plants.
      These results indicate that an increase in the 18:3 level in phospholipids is not
      directly involved in compensation for the diminishment in growth or membrane
      properties observed under low temperatures.

PMID- 9765546
TI  - The role of the alternative oxidase in stabilizing the in vivo reduction state of
      the ubiquinone pool and the activation state of the alternative oxidase 
AB  - A possible function for the alternative (nonphosphorylating) pathway is to
      stabilize the reduction state of the ubiquinone pool (Qr/Qt), thereby avoiding an
      increase in free radical production. If the Qr/Qt were stabilized by the
      alternative pathway, then Qr/Qt should be less stable when the alternative
      pathway is blocked. Qr/Qt increased when we exposed roots of Poa annua (L.) to
      increasing concentrations of KCN (an inhibitor of the cytochrome pathway).
      However, when salicylhydroxamic acid, an inhibitor of the alternative pathway,
      was added at the same time, Qr/Qt increased significantly more. Therefore, we
      conclude that the alternative pathway stabilizes Qr/Qt. Salicylhydroxamic acid
      increasingly inhibited respiration with increasing concentrations of KCN. In the
      experiments described here the alternative oxidase protein was invariably in its
      reduced (high-activity) state. Therefore, changes in the reduction state of the
      alternative oxidase cannot account for an increase in activity of the alternative
      pathway upon titration with KCN. The pyruvate concentration in intact roots
      increased only after the alternative pathway was blocked or the cytochrome
      pathway was severely inhibited. The significance of the pyruvate concentration
      and Qr/Qt on the activity of the alternative pathway in intact roots is
      discussed.

PMID- 9765547
TI  - Two genetically separable phases of growth inhibition induced by blue light in
      Arabidopsis seedlings.
AB  - High fluence-rate blue light (BL) rapidly inhibits hypocotyl growth in
      Arabidopsis, as in other species, after a lag time of 30 s. This growth
      inhibition is always preceded by the activation of anion channels. The membrane
      depolarization that results from the activation of anion channels by BL was only
      30% of the wild-type magnitude in hy4, a mutant lacking the HY4 BL receptor. High
      resolution measurements of growth made with a computer-linked displacement
      transducer or digitized images revealed that BL caused a rapid inhibition of
      growth in wild-type and hy4 seedlings. This inhibition persisted in wild-type
      seedlings during more than 40 h of continuous BL. By contrast, hy4 escaped from
      the initial inhibition after approximately 1 h of BL and grew faster than wild
      type for approximately 30 h. Wild-type seedlings treated with 5-nitro-2-(3
      phenylpropylamino)-benzoic acid, a potent blocker of the BL-activated anion
      channel, displayed rapid growth inhibition, but, similar to hy4, these seedlings
      escaped from inhibition after approximately 1 h of BL and phenocopied the mutant
      for at least 2.5 h. The effects of 5-nitro-2-(3-phenylpropylamino)-benzoic acid
      and the HY4 mutation were not additive. Taken together, the results indicate that
      BL acts through HY4 to activate anion channels at the plasma membrane, causing
      growth inhibition that begins after approximately 1 h. Neither HY4 nor anion
      channels appear to participate greatly in the initial phase of inhibition.

PMID- 9765548
TI  - Purification and characterization of NADP+-linked isocitrate dehydrogenase from
      scots pine . Evidence for different physiological roles of the enzyme in primary
      development 
AB  - NADP+-isocitrate dehydrogenase (NADP+-IDH; EC 1.1.1.42) is involved in the supply
      of 2-oxoglutarate for ammonia assimilation and glutamate synthesis in higher
      plants through the glutamine synthetase/glutamate synthase (GS/GOGAT) cycle. Only
      one NADP+-IDH form of cytosolic localization was detected in green cotyledons of
      pine (Pinus spp.) seedlings. The pine enzyme was purified and exhibited molecular
      and kinetic properties similar to those described for NADP+-IDH from angiosperm,
      with a higher catalytic efficiency (10(5) M-1 s-1) than the deduced efficiencies
      for GS and GOGAT in higher plants. A polyclonal antiserum was raised against pine
      NADP+-IDH and used to assess protein expression in the seedlings. Steady-state
      levels of NADP+-IDH were coordinated with GS during seed germination and were
      associated with GS/GOGAT enzymes during chloroplast biogenesis, suggesting that
      NADP+-IDH is involved in the provision of carbon skeletons for the synthesis of
      nitrogen-containing molecules. However, a noncoordinated pattern of NADP+-IDH and
      GS/GOGAT was observed in advanced stages of cotyledon development and in the
      hypocotyl. A detailed analysis in hypocotyl sections revealed that NADP+-IDH
      abundance was inversely correlated with the presence of GS, GOGAT, and ribulose
      1,5-bisphosphate carboxylase/oxygenase but was associated with the
      differentiation of the organ. These results cannot be explained by the accepted
      role of the enzyme in nitrogen assimilation and strongly suggest that NADP+-IDH
      may have other, as-yet-unknown, biological functions.

PMID- 9765549
TI  - Carbohydrate and amino acid metabolism in the eucalyptus globulus-pisolithus
      tinctorius ectomycorrhiza during glucose utilization 
AB  - The metabolism of [1-13C]glucose in Pisolithus tinctorius cv Coker & Couch, in
      uninoculated seedlings of Eucalyptus globulus bicostata ex Maiden cv Kirkp., and
      in the E. globulus-P. tinctorius ectomycorrhiza was studied using nuclear
      magnetic resonance spectroscopy. In roots of uninoculated seedlings, the 13C
      label was mainly incorporated into sucrose and glutamine. The ratio (13C3 +
      13C2)/13C4 of glutamine was approximately 1.0 during the time-course experiment,
      indicating equivalent contributions of phosphoenolpyruvate carboxylase and
      pyruvate dehydrogenase to the production of alpha-ketoglutarate used for
      synthesis of this amino acid. In free-living P. tinctorius, most of the 13C label
      was incorporated into mannitol, trehalose, glutamine, and alanine, whereas
      arabitol, erythritol, and glutamate were weakly labeled. Amino acid biosynthesis
      was an important sink of assimilated 13C (43%), and anaplerotic CO2 fixation
      contributed 42% of the C flux entering the Krebs cycle. In ectomycorrhizae,
      sucrose accumulation was decreased in the colonized roots compared with
      uninoculated control plants, whereas 13C incorporation into arabitol and
      erythritol was nearly 4-fold higher in the symbiotic mycelium than in the free
      living fungus. It appears that fungal utilization of glucose in the symbiotic
      state is altered and oriented toward the synthesis of short-chain polyols.

PMID- 9765550
TI  - Superoxide dismutase in Arabidopsis: an eclectic enzyme family with disparate
      regulation and protein localization.
AB  - A number of environmental stresses can lead to enhanced production of superoxide
      within plant tissues, and plants are believed to rely on the enzyme superoxide
      dismutase (SOD) to detoxify this reactive oxygen species. We have identified
      seven cDNAs and genes for SOD in Arabidopsis. These consist of three CuZnSODs
      (CSD1, CSD2, and CSD3), three FeSODs (FSD1, FSD2, and FSD3), and one MnSOD
      (MSD1). The chromosomal location of these seven SOD genes has been established.
      To study this enzyme family, antibodies were generated against five proteins:
      CSD1, CSD2, CSD3, FSD1, and MSD1. Using these antisera and nondenaturing
      polyacrylamide gel electrophoresis enzyme assays, we identified protein and
      activity for two CuZnSODs and for FeSOD and MnSOD in Arabidopsis rosette tissue.
      Additionally, subcellular fractionation studies revealed the presence of CSD2 and
      FeSOD protein within Arabidopsis chloroplasts. The seven SOD mRNAs and the four
      proteins identified were differentially regulated in response to various light
      regimes, ozone fumigation, and ultraviolet-B irradiation. To our knowledge, this
      is the first report of a large-scale analysis of the regulation of multiple SOD
      proteins in a plant species.

PMID- 9765551
TI  - Rapid Up-regulation of HKT1, a high-affinity potassium transporter gene, in roots
      of barley and wheat following withdrawal of potassium 
AB  - High-affinity K+ uptake in plant roots is rapidly up-regulated when K+ is
      withheld and down-regulated when K+ is resupplied. These processes make important
      contributions to plant K+ homeostasis. A cDNA coding for a high-affinity K+
      transporter, HKT1, was earlier cloned from wheat (Triticum aestivum L.) roots and
      functionally characterized. We demonstrate here that in both barley (Hordeum
      vulgare L.) and wheat roots, a rapid and large up-regulation of HKT1 mRNA levels
      resulted when K+ was withdrawn from growth media. This effect was specific for
      K+; withholding N caused a modest reduction of HKT1 mRNA levels. Up-regulation of
      HKT1 transcript levels in barley roots occurred within 4 h of removing K+, which
      corresponds to the documented increase of high-affinity K+ uptake in roots
      following removal of K+. Increased expression of HKT1 mRNA was evident before a
      decline in total root K+ concentration could be detected. Resupply of 1 mM K+ was
      sufficient to strongly reduce HKT1 transcript levels. In wheat root cortical
      cells, both membrane depolarizations in response to 100 &mgr;M K+, Cs+, and Rb+,
      and high-affinity K+ uptake were enhanced by K+ deprivation. Thus, in both plant
      systems the observed physiological changes associated with manipulating external
      K+ supply were correlated with levels of HKT1 mRNA expression. Implications of
      these findings for K+ sensing and regulation of the HKT1 mRNA levels in plant
      roots are discussed.

PMID- 9765553
TI  - Differential expression of alternative oxidase genes in soybean cotyledons during
      postgerminative development 
AB  - The expression of the alternative oxidase (AOX) was investigated during cotyledon
      development in soybean (Glycine max [L.] Merr.) seedlings. The total amount of
      AOX protein increased throughout development, not just in earlier stages as
      previously thought, and was correlated with the increase in capacity of the
      alternative pathway. Each AOX isoform (AOX1, AOX2, and AOX3) showed a different
      developmental trend in mRNA abundance, such that the increase in AOX protein and
      capacity appears to involve a shift in gene expression from AOX2 to AOX3. As the
      cotyledons aged, the size of the mitochondrial ubiquinone pool decreased. We
      discuss how this and other factors may affect the alternative pathway activity
      that results from the developmental regulation of AOX expression.

PMID- 9765554
TI  - Acclimation of photosynthesis to elevated CO2 under low-nitrogen nutrition is
      affected by the capacity for assimilate utilization. Perennial ryegrass under
      free-Air CO2 enrichment 
AB  - Acclimation of photosynthesis to elevated CO2 has previously been shown to be
      more pronounced when N supply is poor. Is this a direct effect of N or an
      indirect effect of N by limiting the development of sinks for photoassimilate?
      This question was tested by growing a perennial ryegrass (Lolium perenne) in the
      field under elevated (60 Pa) and current (36 Pa) partial pressures of CO2 (pCO2)
      at low and high levels of N fertilization. Cutting of this herbage crop at 4- to
      8-week intervals removed about 80% of the canopy, therefore decreasing the ratio
      of photosynthetic area to sinks for photoassimilate. Leaf photosynthesis, in vivo
      carboxylation capacity, carbohydrate, N, ribulose-1,5-bisphosphate
      carboxylase/oxygenase, sedoheptulose-1,7-bisphosphatase, and chloroplastic
      fructose-1, 6-bisphosphatase levels were determined for mature lamina during two
      consecutive summers. Just before the cut, when the canopy was relatively large,
      growth at elevated pCO2 and low N resulted in significant decreases in
      carboxylation capacity and the amount of ribulose-1,5-bisphosphate
      carboxylase/oxygenase protein. In high N there were no significant decreases in
      carboxylation capacity or proteins, but chloroplastic fructose-1,6-bisphosphatase
      protein levels increased significantly. Elevated pCO2 resulted in a marked and
      significant increase in leaf carbohydrate content at low N, but had no effect at
      high N. This acclimation at low N was absent after the harvest, when the canopy
      size was small. These results suggest that acclimation under low N is caused by
      limitation of sink development rather than being a direct effect of N supply on
      photosynthesis.

PMID- 9765552
TI  - Comparative analysis of the regulation of expression and structures of two
      evolutionarily divergent genes for Delta1-pyrroline-5-carboxylate synthetase from
      tomato.
AB  - We isolated two tomato (Lycopersicon esculentum) cDNA clones, tomPRO1 and
      tomPRO2, specifying Delta1-pyrroline-5-carboxylate synthetase (P5CS), the first
      enzyme of proline (Pro) biosynthesis. tomPRO1 is unusual because it resembles
      prokaryotic polycistronic operons (M.G. Garcia-Rios, T. Fujita, P.C. LaRosa, R.D.
      Locy, J.M. Clithero, R.A. Bressan, L.N. Csonka [1997] Proc Natl Acad Sci USA 94:
      8249-8254), whereas tomPRO2 encodes a full-length P5CS. We analyzed the
      accumulation of Pro and the tomPRO1 and tomPRO2 messages in response to NaCl
      stress and developmental signals. Treatment with 200 mM NaCl resulted in a >60
      fold increase in Pro levels in roots and leaves. However, there was a <3-fold
      increase in the accumulation of the tomPRO2 message and no detectable induction
      in the level of the tomPRO1 message in response to NaCl stress. Although pollen
      contained approximately 100-fold higher levels of Pro than other plant tissues,
      there was no detectable increase in the level of either message in pollen. We
      conclude that transcriptional regulation of these genes for P5CS is probably not
      important for the osmotic or pollen-specific regulation of Pro synthesis in
      tomato. Using restriction fragment-length polymorphism mapping, we determined the
      locations of tomPRO1 and tomPRO2 loci in the tomato nuclear genome. Sequence
      comparison suggested that tomPRO1 is similar to prokaryotic P5CS loci, whereas
      tomPRO2 is closely related to other eukaryotic P5CS genes.

PMID- 9765555
TI  - Domains of a transit sequence required for in vivo import in Arabidopsis
      chloroplasts.
AB  - Nuclear-encoded precursors of chloroplast proteins are synthesized with an amino
      terminal cleavable transit sequence, which contains the information for
      chloroplastic targeting. To determine which regions of the transit sequence are
      most important for its function, the chloroplast uptake and processing of a full
      length ferredoxin precursor and four mutants with deletions in adjacent regions
      of the transit sequence were analyzed. Arabidopsis was used as an experimental
      system for both in vitro and in vivo import. The full-length wild-type precursor
      translocated efficiently into isolated Arabidopsis chloroplasts, and upon
      expression in transgenic Arabidopsis plants only mature-sized protein was
      detected, which was localized inside the chloroplast. None of the deletion
      mutants was imported in vitro. By analyzing transgenic plants, more subtle
      effects on import were observed. The most N-terminal deletion resulted in a fully
      defective transit sequence. Two deletions in the middle region of the transit
      sequence allowed translocation into the chloroplast, although with reduced
      efficiencies. One deletion in this region strongly reduced mature protein
      accumulation in older plants. The most C-terminal deletion was translocated but
      resulted in defective processing. These results allow the dissection of the
      transit sequence into separate functional regions and give an in vivo basis for a
      domain-like structure of the ferredoxin transit sequence.

PMID- 9765556
TI  - Rapid regulation by acid pH of cell wall adjustment and leaf growth in maize
      plants responding to reversal of water stress 
AB  - The role of acid secretion in regulating short-term changes in growth rate and
      wall extensibility was investigated in emerging first leaves of intact, water
      stressed maize (Zea mays L.) seedlings. A novel approach was used to measure leaf
      responses to injection of water or solutions containing potential regulators of
      growth. Both leaf elongation and wall extensibility, as measured with a whole
      plant creep extensiometer, increased dramatically within minutes of injecting
      water, 0.5 mM phosphate, or strong (50 mM) buffer solutions with pH </= 5.0 into
      the cell-elongation zone of water-stressed leaves. In contrast, injecting buffer
      solutions at pH >/= 5.5 inhibited these fast responses. Solutions containing 0.5
      mM orthovanadate or erythrosin B to inhibit wall acidification by plasma membrane
      H+-ATPases were also inhibitory. Thus, cell wall extensibility and leaf growth in
      water-stressed plants remained inhibited, despite the increased availability of
      (injected) water when accompanying increases in acid-induced wall loosening were
      prevented. However, growth was stimulated when pH 4.5 buffers were included with
      the vanadate injections. These findings suggest that increasing the availability
      of water to expanding cells in water-stressed leaves signals rapid increases in
      outward proton pumping by plasma membrane H+-ATPases. Resultant increases in cell
      wall extensibility participate in the regulation of water uptake, cell expansion,
      and leaf growth.

PMID- 9765557
TI  - Characterization of multiple regions involved in replication and mobilization of
      plasmid pNZ4000 coding for exopolysaccharide production in Lactococcus lactis.
AB  - We characterized the regions involved in replication and mobilization of the 40
      kb plasmid pNZ4000, encoding exopolysaccharide (EPS) production in Lactococcus
      lactis NIZO B40. The plasmid contains four highly conserved replication regions
      with homologous rep genes (repB1, repB2, repB3, and repB4) that belong to the
      lactococcal theta replicon family. Subcloning of each replicon individually
      showed that all are functional and compatible in L. lactis. Plasmid pNZ4000 and
      genetically labeled derivatives could be transferred to different L. lactis
      strains by conjugation, and pNZ4000 was shown to be a mobilization plasmid. Two
      regions involved in mobilization were identified near two of the replicons; both
      included an oriT sequence rich in inverted repeats. Conjugative mobilization of
      the nonmobilizable plasmid pNZ124 was promoted by either one of these oriT
      sequences, demonstrating their functionality. One oriT sequence was followed by a
      mobA gene, coding for a trans-acting protein, which increased the frequency of
      conjugative transfer 100-fold. The predicted MobA protein and the oriT sequences
      show protein and nucleotide similarity, respectively, with the relaxase and with
      the inverted repeat and nic site of the oriT from the Escherichia coli plasmid
      R64. The presence on pNZ4000 of four functional replicons, two oriT sequences,
      and several insertion sequence-like elements strongly suggests that this EPS
      plasmid is a naturally occurring cointegrate.

PMID- 9765558
TI  - Iron-responsive gene regulation in a campylobacter jejuni fur mutant.
AB  - The expression of iron-regulated systems in gram-negative bacteria is generally
      controlled by the Fur protein, which represses the transcription of iron
      regulated promoters by using Fe2+ as a cofactor. Mutational analysis of the
      Campylobacter jejuni fur gene was carried out by generation of a set of mutant
      copies of fur which had a kanamycin or chloramphenicol resistance gene introduced
      into the regions encoding the N and C termini of the Fur protein. The mutated
      genes were recombined into the C. jejuni NCTC 11168 chromosome, and putative
      mutants were confirmed by Southern hybridization. C. jejuni mutants were obtained
      only when the resistance genes were transcribed in the same orientation as the
      fur gene. The C. jejuni fur mutant grew slower than the parental strain.
      Comparison of protein profiles of fractionated C. jejuni cells grown in low- or
      high-iron medium indicated derepressed expression of three iron-regulated outer
      membrane proteins with molecular masses of 70, 75, and 80 kDa. Characterization
      by N-terminal amino acid sequencing showed the 75-kDa protein to be identical to
      CfrA, a Campylobacter coli siderophore receptor homologue, whereas the 70-kDa
      protein was identified as a new siderophore receptor homologue. Periplasmic
      fractions contained four derepressed proteins with molecular masses of 19, 29,
      32, and 36 kDa. The 19-kDa protein has been previously identified, but its
      function is unknown. The cytoplasmic fraction contained two iron-repressed and
      two iron-induced proteins with molecular masses of 26, 55, 31, and 40 kDa,
      respectively. The two iron-repressed proteins have been previously identified as
      the oxidative stress defense proteins catalase (KatA) and alkyl hydroperoxide
      reductase (AhpC). AhpC and KatA were still iron regulated in the fur mutant,
      suggesting the presence of Fur-independent iron regulation. Further analysis of
      the C. jejuni iron and Fur regulons by using two-dimensional gel electrophoresis
      demonstrated the total number of iron- and Fur-regulated proteins to be lower
      than for other bacterial pathogens.

PMID- 9765559
TI  - Domain structure of the ATP-binding-cassette protein MalK of salmonella
      typhimurium as assessed by coexpressed half molecules and LacK'-'MalK chimeras.
AB  - ATP-binding-cassette (ABC) subunit MalK of the binding protein-dependent
      transport system for maltose of Salmonella typhimurium and Escherichia coli is
      crucial to the transport process but also exhibits a repressing activity on other
      genes of the maltose regulon. The latter function has been attributed to a
      carboxy-terminal extension by which MalK differs in length from a prototype ABC
      protein. In order to define the boundaries of putative functional domains of
      MalK, we have analyzed pairs of N- and C-terminally truncated MalK proteins of S.
      typhimurium. Coexpressed half molecules of about equal lengths (MalKN1: residues
      1 to 179; MalKC1: residues 179 to 369) restored the transport activity of a malK
      strain and displayed substantial regulatory activity. The same regulatory
      activity was obtained when malKC1 was expressed separately. These results
      indicate that a covalent linkage is not absolutely essential for function and
      that the protein might be composed of two structurally distinct entities. To
      elucidate further the minimal structural requirements for the regulatory function
      of MalK, we have studied chimeric proteins that have C-terminal portions of MalK
      fused to the corresponding amino-terminal fragments of its close homolog LacK.
      Functional analyses revealed that a fusion containing only the C-terminal
      extension of MalK (Q263 to V369) is sufficient to display half-maximal regulatory
      activity. This activity increased with the lengths of the MalK portions present
      in the chimeras. Furthermore, the failure of two chimeras to support maltose
      transport suggests a structurally critical region between residues 243 and 264.
      In the absence of a crystal structure, this work contributes to the understanding
      of the multiple functions of MalK.

PMID- 9765560
TI  - Identification and characterization of IS1411, a new insertion sequence which
      causes transcriptional activation of the phenol degradation genes in Pseudomonas
      putida.
AB  - A new insertion sequence (IS element), IS1411, was identified downstream of the
      phenol degradation genes pheBA that originated from plasmid DNA of Pseudomonas
      sp. strain EST1001. According to sequence analysis, IS1411 belongs to a new
      family of IS elements that has recently been named the ISL3 family (J. Mahillon
      and M. Chandler, Microbiol. Mol. Biol. Rev. 62:725-774, 1998). IS1411 generates 8
      bp duplication of the target DNA and carries 24-bp inverted repeats (IRs), highly
      homologous to the IRs of other IS elements belonging to this family. IS1411 was
      discovered as a result of insertional activation of promoterless pheBA genes in
      Pseudomonas putida due to the presence of outward-directed promoters at the left
      end of IS1411. Both promoters located on the IS element have sequences that are
      similar to the consensus sequence of Escherichia coli sigma70. IS1411 can produce
      IS circles, and the circle formation is enhanced when two copies of the element
      are present in the same plasmid.

PMID- 9765561
TI  - Conserved structural regions involved in the catalytic mechanism of Escherichia
      coli K-12 WaaO (RfaI).
AB  - Escherichia coli K-12 WaaO (formerly known as RfaI) is a nonprocessive alpha-1,3
      glucosyltransferase, involved in the synthesis of the R core of
      lipopolysaccharide. By comparing the amino acid sequence of WaaO with those of 11
      homologous alpha-glycosyltransferases, four strictly conserved regions, I, II,
      III, and IV, were identified. Since functionally related transferases are
      predicted to have a similar architecture in the catalytic sites, it is assumed
      that these four regions are directly involved in the formation of alpha
      glycosidic linkage from alpha-linked nucleotide diphospho-sugar donor.
      Hydrophobic cluster analysis revealed a conserved domain at the N termini of
      these alpha-glycosyltransferases. This domain was similar to that previously
      reported for beta-glycosyltransferases. Thus, this domain is likely to be
      involved in the formation of beta-glycosidic linkage between the donor sugar and
      the enzyme at the first step of the reaction. Site-directed mutagenesis analysis
      of E. coli K-12 WaaO revealed four critical amino acid residues.

PMID- 9765563
TI  - MinCD proteins control the septation process during sporulation of Bacillus
      subtilis.
AB  - Mutation of the divIVB locus in Bacillus subtilis causes misplacement of the
      septum during cell division and allows the formation of anucleate minicells. The
      divIVB locus contains five open reading frames (ORFs). The last two ORFs (minCD)
      are homologous to minC and minD of Escherichia coli but a minE homolog is lacking
      in B. subtilis. There is some similarity between minicell formation and the
      asymmetric septation that normally occurs during sporulation in terms of polar
      septum localization. However, it has been proposed that MinCD has no essential
      role in sporulation septum formation. We have used electron microscopic studies
      to show septation events during sporulation in some minD strains. We have
      observed an unusually thin septum at the midcell position in minD and also in
      minD spoIIE71 mutant cells. Fluorescence microscopy also localized a SpoIIE-green
      fluorescent protein fusion protein at the midcell site in minD cells. We propose
      that the MinCD complex plays an important role in asymmetric septum formation
      during sporulation of B. subtilis cells.

PMID- 9765562
TI  - Regulation of the Bacillus subtilis GlcT antiterminator protein by components of
      the phosphotransferase system.
AB  - Bacillus subtilis utilizes glucose as the preferred source of carbon and energy.
      The sugar is transported into the cell by a specific permease of the
      phosphoenolpyruvate:sugar phosphotransferase system (PTS) encoded by the ptsGHI
      operon. Expression of this operon is induced by glucose and requires the action
      of a positive transcription factor, the GlcT antiterminator protein. Glucose
      availability is sensed by glucose-specific enzyme II (EIIGlc), the product of
      ptsG. In the absence of inducer, the glucose permease negatively controls the
      activity of the antiterminator. The GlcT antiterminator has a modular structure.
      The isolated N-terminal part contains the RNA-binding protein and acts as a
      constitutively acting antiterminator. GlcT contains two PTS regulation domains
      (PRDs) at the C terminus. One (PRD-I) is the target of negative control exerted
      by EIIGlc. A conserved His residue (His-104 in GlcT) is involved in inactivation
      of GlcT in the absence of glucose. It was previously proposed that PRD-containing
      transcriptional antiterminators are phosphorylated and concomitantly inactivated
      in the absence of the substrate by their corresponding PTS permeases. The results
      obtained with B. subtilis glucose permease with site-specific mutations suggest,
      however, that the permease might modulate the phosphorylation reaction without
      being the phosphate donor.

PMID- 9765564
TI  - Identification of Candida albicans ALS2 and ALS4 and localization of als proteins
      to the fungal cell surface.
AB  - Additional genes in the growing ALS family of Candida albicans were isolated by
      PCR screening of a genomic fosmid library with primers designed from the
      consensus tandem-repeat sequence of ALS1. This procedure yielded fosmids encoding
      ALS2 and ALS4. ALS2 and ALS4 conformed to the three-domain structure of ALS
      genes, which consists of a central domain of tandemly repeated copies of a 108-bp
      motif, an upstream domain of highly conserved sequences, and a domain of
      divergent sequences 3' of the tandem repeats. Alignment of five predicted Als
      protein sequences indicated conservation of N- and C-terminal hydrophobic regions
      which have the hallmarks of secretory signal sequences and
      glycosylphosphatidylinositol addition sites, respectively. Heterologous
      expression of an N-terminal fragment of Als1p in Saccharomyces cerevisiae
      demonstrated function of the putative signal sequence with cleavage following
      Ala17. This signal sequence cleavage site was conserved in the four other Als
      proteins analyzed, suggesting identical processing of each protein. Primary
      structure features of the five Als proteins suggested a cell-surface
      localization, which was confirmed by indirect immunofluorescence with an anti-Als
      antiserum. Staining was observed on mother yeasts and germ tubes, although the
      intensity of staining on the mother yeast decreased with elongation of the germ
      tube. Similar to other ALS genes, ALS2 and ALS4 were differentially regulated.
      ALS4 expression was correlated with the growth phase of the culture; ALS2
      expression was not observed under many different in vitro growth conditions. The
      data presented here demonstrate that ALS genes encode cell-surface proteins and
      support the conclusion that the size and number of Als proteins on the C.
      albicans cell surface vary with strain and growth conditions.

PMID- 9765565
TI  - Nitrogen and oxygen regulation of Bacillus subtilis nasDEF encoding NADH
      dependent nitrite reductase by TnrA and ResDE.
AB  - The nitrate and nitrite reductases of Bacillus subtilis have two different
      physiological functions. Under conditions of nitrogen limitation, these enzymes
      catalyze the reduction of nitrate via nitrite to ammonia for the anabolic
      incorporation of nitrogen into biomolecules. They also function catabolically in
      anaerobic respiration, which involves the use of nitrate and nitrite as terminal
      electron acceptors. Two distinct nitrate reductases, encoded by narGHI and nasBC,
      function in anabolic and catabolic nitrogen metabolism, respectively. However, as
      reported herein, a single NADH-dependent, soluble nitrite reductase encoded by
      the nasDE genes is required for both catabolic and anabolic processes. The nasDE
      genes, together with nasBC (encoding assimilatory nitrate reductase) and nasF
      (required for nitrite reductase siroheme cofactor formation), constitute the nas
      operon. Data presented show that transcription of nasDEF is driven not only by
      the previously characterized nas operon promoter but also from an internal
      promoter residing between the nasC and nasD genes. Transcription from both
      promoters is activated by nitrogen limitation during aerobic growth by the
      nitrogen regulator, TnrA. However, under conditions of oxygen limitation, nasDEF
      expression and nitrite reductase activity were significantly induced. Anaerobic
      induction of nasDEF required the ResDE two-component regulatory system and the
      presence of nitrite, indicating partial coregulation of NasDEF with the
      respiratory nitrate reductase NarGHI during nitrate respiration.

PMID- 9765566
TI  - The NADP-dependent methylene tetrahydromethanopterin dehydrogenase in
      Methylobacterium extorquens AM1.
AB  - An NADP-dependent methylene tetrahydromethanopterin (H4MPT) dehydrogenase has
      recently been proposed to be involved in formaldehyde oxidation to CO2 in
      Methylobacterium extorquens AM1. We report here on the purification of this novel
      enzyme to apparent homogeneity. Via the N-terminal amino acid sequence, it was
      identified to be the mtdA gene product. The purified enzyme catalyzed the
      dehydrogenation of methylene H4MPT with NADP+ rather than with NAD+, with a
      specific activity of approximately 400 U/mg of protein. It also catalyzed the
      dehydrogenation of methylene tetrahydrofolate (methylene H4F) with NADP+. With
      methylene H4F as the substrate, however, the specific activity (26 U/mg) and the
      catalytic efficiency (Vmax/Km) were approximately 20-fold lower than with
      methylene H4MPT. Whereas the dehydrogenation of methylene H4MPT (E0 = -390 mV)
      with NADP+ (E0 = -320 mV) proceeded essentially irreversibly, the dehydrogenation
      of methylene H4F (E0 = -300 mV) was fully reversible. Comparison of the primary
      structure of the NADP-dependent dehydrogenase from M. extorquens AM1 with those
      of methylene H4F dehydrogenases from other bacteria and eucarya and with those of
      methylene H4MPT dehydrogenases from methanogenic archaea revealed only marginally
      significant similarity (<15%).

PMID- 9765567
TI  - A chaperone in the HSP70 family controls production of extracellular fibrils in
      Myxococcus xanthus.
AB  - Three independent Tn5-lac insertions in the S1 locus of Myxococcus xanthus
      inactivate the sglK gene, which is nonessential for growth but required for
      social motility and multicellular development. The sequence of sglK reveals that
      it encodes a homologue of the chaperone HSP70 (DnaK). The sglK gene is
      cotranscribed with the upstream grpS gene, which encodes a GrpE homologue. Unlike
      sglK, grpS is not required for social motility or development. Wild-type M.
      xanthus is encased in extracellular polysaccharide filaments associated with the
      multimeric fibrillin protein. Mutations in sglK inhibit cell cohesion, the
      binding of Congo red, and the synthesis or secretion of fibrillin, indicating
      that sglK mutants do not make fibrils. The fibR gene, located immediately
      upstream of the grpS-sglK operon, encodes a product which is predicted to have a
      sequence similar to those of the repressors of alginate biosynthesis in
      Pseudomonas aeruginosa and Pseudomonas putida. Inactivation of fibR leads to the
      overproduction of fibrillin, suggesting that M. xanthus fibril production and
      Pseudomonas alginate production are regulated in analogous ways. M. xanthus and
      Pseudomonas exopolysaccharides may play similar roles in a mechanism of social
      motility conserved in these gram-negative bacteria.

PMID- 9765568
TI  - Legionella pneumophila catalase-peroxidases: cloning of the katB gene and studies
      of KatB function.
AB  - Legionella pneumophila, the causative organism of Legionnaires' pneumonia, is
      spread by aerosolization from man-made reservoirs, e.g. , water cooling towers
      and air conditioning ducts, whose nutrient-poor conditions are conducive to
      entrance into stationary phase. Exposure to starvation conditions is known to
      induce several virulence traits in L. pneumophila. Since catalase-peroxidases
      have been extremely useful markers of the stationary-phase response in many
      bacterial species and may be an avenue for identifying virulence genes in L.
      pneumophila, an investigation of these enzymes was initiated. L. pneumophila was
      shown to contain two bifunctional catalase-peroxidases and to lack monofunctional
      catalase and peroxidase. The gene encoding the KatB catalase-peroxidase was
      cloned and sequenced, and lacZ fusion and null mutant strains were constructed.
      Null mutants in katB are delayed in the infection and lysis of cultured
      macrophage-like cell lines. KatB is similar to the KatG catalase-peroxidase of
      Escherichia coli in its 20-fold induction during exponential growth and in
      playing a role in resistance to hydrogen peroxide. Analysis of the changes in
      katB expression and in the total catalase and peroxidase activity during growth
      indicates that the 8- to 10-fold induction of peroxidase activity that occurs in
      stationary phase is attributable to KatA, the second L. pneumophila catalase
      peroxidase.

PMID- 9765569
TI  - Escherichia coli promoters with UP elements of different strengths: modular
      structure of bacterial promoters.
AB  - The alpha subunit of Escherichia coli RNA polymerase (RNAP) participates in
      promoter recognition through specific interactions with UP element DNA, a region
      upstream of the recognition hexamers for the sigma subunit (the -10 and -35
      hexamers). UP elements have been described in only a small number of promoters,
      including the rRNA promoter rrnB P1, where the sequence has a very large (30- to
      70-fold) effect on promoter activity. Here, we analyzed the effects of upstream
      sequences from several additional E. coli promoters (rrnD P1, rrnB P2, lambda pR,
      lac, merT, and RNA II). The relative effects of different upstream sequences were
      compared in the context of their own core promoters or as hybrids to the lac core
      promoter. Different upstream sequences had different effects, increasing
      transcription from 1.5- to approximately 90-fold, and several had the properties
      of UP elements: they increased transcription in vitro in the absence of accessory
      protein factors, and transcription stimulation required the C-terminal domain of
      the RNAP alpha subunit. The effects of the upstream sequences correlated
      generally with their degree of similarity to an UP element consensus sequence
      derived previously. Protection of upstream sequences by RNAP in footprinting
      experiments occurred in all cases and was thus not a reliable indicator of UP
      element strength. These data support a modular view of bacterial promoters in
      which activity reflects the composite effects of RNAP interactions with
      appropriately spaced recognition elements (-10, -35, and UP elements), each of
      which contributes to activity depending on its similarity to the consensus.

PMID- 9765571
TI  - Analogs of the autoinducer 3-oxooctanoyl-homoserine lactone strongly inhibit
      activity of the TraR protein of Agrobacterium tumefaciens.
AB  - The TraR and TraI proteins of Agrobacterium tumefaciens mediate cell-density
      dependent expression of the Ti plasmid tra regulon. TraI synthesizes the
      autoinducer pheromone N-(3-oxooctanoyl)-L-homoserine lactone (3-oxo-C8-HSL),
      while TraR is an 3-oxo-C8-HSL-responsive transcriptional activator. We have
      compared the abilities of 3-oxo-C8-HSL and 32 related compounds to activate
      expression of a TraR-regulated promoter. In a strain that expresses wild-type
      levels of TraR, only 3-oxo-C8-HSL was strongly stimulatory, four compounds were
      detectably active only at high concentrations, and the remaining 28 compounds
      were inactive. Furthermore, many of these compounds were potent antagonists. In
      contrast, almost all of these compounds were stimulatory in a congenic strain
      that overexpresses TraR and no compound was a potent antagonist. We propose a
      model in which autoinducers enhance the affinity of TraR either for other TraR
      monomers or for DNA binding sites and that overexpression of TraR potentiates
      this interaction by mass action. Wild-type A. tumefaciens released a rather broad
      spectrum of autoinducers, including several that antagonize induction of a wild
      type strain. However, under all conditions tested, 3-oxo-C8-HSL was more abundant
      than any other analog, indicating that other released autoinducers do not
      interfere with tra gene induction. We conclude that (i) in wild-type strains,
      only 3-oxo-C8-HSL significantly stimulates tra gene expression, while many
      autoinducer analogs are potent antagonists; (ii) TraR overexpression increases
      agonistic activity of autoinducer analogs, allowing sensitive biodetection of
      many autoinducers; and (iii) autoinducer stimulatory activity is potentiated by
      TraR overproduction, suggesting that autoinducers may shift an equilibrium
      between TraR monomers and dimers or oligomers. When autoinducer specificities of
      other quorum-sensing proteins are tested, care should be taken not to overexpress
      those proteins.

PMID- 9765570
TI  - Flk couples flgM translation to flagellar ring assembly in Salmonella
      typhimurium.
AB  - The hook-basal body (HBB) is a key intermediate structure in the flagellar
      assembly pathway in Salmonella typhimurium. The FlgM protein inhibits the
      flagellum-specific transcription factor sigma28 in the absence of the intact HBB
      structure and is secreted out of the cell following HBB completion. The flk gene
      encodes a positive regulator of the activity of FlgM at an assembly step just
      prior to HBB completion: at the point of assembly of the P- and L-rings. FlgM
      inhibition of sigma28-dependent class 3 flagellar gene transcription was relieved
      in P- and L-ring assembly mutants (flgA, flgH, and flgI) by introduction of a
      null mutation in the flk gene (J. E. Karlinsey et al., J. Bacteriol. 179:2389
      2400, 1997). In P- and L-ring mutant strains, recessive mutations in flk resulted
      in a reduction in intracellular FlgM levels to those seen in wild-type (Fla+)
      strains. The reduction in intracellular FlgM levels by mutations in the flk gene
      was concomitant with a 10-fold increase in transcription of the flgMN operon
      compared to that of the isogenic flk+ strain, while transcription of the flgAMN
      operon was unaffected. This was true for both direct measurement of the flgAMN
      and flgMN mRNA transcripts by RNase T2 protection assays and for lac operon
      fusions to either the flgAMN or flgMN promoter. Loss of Flk did not allow
      secretion of FlgM through basal-body structures lacking the P- and L-rings.
      Intracellular FlgM was stable to proteolysis, and turnover occurred primarily
      after export out of the cell. Loss of Flk did not result in increased FlgM
      turnover in either P- or L-ring mutant strains. With lacZ translational fusions
      to flgM, a null mutation in flk resulted in a significant reduction of flgM-lacZ
      mRNA translation, expressed from the class 3 flgMN promoter, in P- and L-ring
      mutant strains. No reduction in either flgAMN or flgMN mRNA stability was
      measured in the absence of Flk in Fla+, ring mutant, or HBB deletion strains. We
      conclude that the reduction in the intracellular FlgM levels by mutation in the
      flk gene is only at the level of flgM mRNA translation.

PMID- 9765572
TI  - Methanococcus jannaschii flap endonuclease: expression, purification, and
      substrate requirements.
AB  - The flap endonuclease (FEN) of the hyperthermophilic archaeon Methanococcus
      jannaschii was expressed in Escherichia coli and purified to homogeneity. FEN
      retained activity after preincubation at 95 degrees C+ for 15 min. A pseudo-Y
      shaped substrate was formed by hybridization of two partially complementary
      oligonucleotides. FEN cleaved the strand with the free 5' end adjacent to the
      single-strand-duplex junction. Deletion of the free 3' end prevented cleavage.
      Hybridization of a complementary oligonucleotide to the free 3' end moved the
      cleavage site by 1 to 2 nucleotides. Hybridization of excess complementary
      oligonucleotide to the free 5' end failed to block cleavage, although this
      substrate was refractory to cleavage by the 5'-3' exonuclease activity of Taq DNA
      polymerase. For verification, the free 5' end was replaced by an internally
      labeled hairpin structure. This structure was a substrate for FEN but became a
      substrate for Taq DNA polymerase only after exonucleolytic cleavage had
      destabilized the hairpin. A circular duplex substrate with a 5' single-stranded
      branch was formed by primer extension of a partially complementary
      oligonucleotide on virion phiX174. This denaturation-resistant substrate was used
      to examine the effects of temperature and solution properties, such as pH, salt,
      and divalent ion concentration on the turnover number of the enzyme.

PMID- 9765574
TI  - Fumarate regulation of gene expression in Escherichia coli by the DcuSR (dcuSR
      genes) two-component regulatory system.
AB  - In Escherichia coli the genes encoding the anaerobic fumarate respiratory system
      are transcriptionally regulated by C4-dicarboxylates. The regulation is effected
      by a two-component regulatory system, DcuSR, consisting of a sensory histidine
      kinase (DcuS) and a response regulator (DcuR). DcuS and DcuR are encoded by the
      dcuSR genes (previously yjdHG) at 93.7 min on the calculated E. coli map.
      Inactivation of the dcuR and dcuS genes caused the loss of C4-dicarboxylate
      stimulated synthesis of fumarate reductase (frdABCD genes) and of the anaerobic
      fumarate-succinate antiporter DcuB (dcuB gene). DcuS is predicted to contain a
      large periplasmic domain as the supposed site for C4-dicarboxylate sensing.
      Regulation by DcuR and DcuS responded to the presence of the C4-dicarboxylates
      fumarate, succinate, malate, aspartate, tartrate, and maleate. Since maleate is
      not taken up by the bacteria under these conditions, the carboxylates presumably
      act from without. Genes of the aerobic C4-dicarboxylate pathway encoding
      succinate dehydrogenase (sdhCDAB) and the aerobic succinate carrier (dctA) are
      only marginally or negatively regulated by the DcuSR system. The CitAB two
      component regulatory system, which is highly similar to DcuSR, had no effect on
      C4-dicarboxylate regulation of any of the genes.

PMID- 9765573
TI  - Molecular cloning and expression analysis of the Rhodobacter capsulatus sodB
      gene, encoding an iron superoxide dismutase.
AB  - Genetic complementation of a sodA sodB Escherichia coli mutant strain was used to
      clone Rhodobacter capsulatus genes involved in detoxification of superoxide
      radicals. After sequence analysis, 1 of the 16 identical clones obtained by this
      selection procedure was shown to contain an open reading frame with sequence
      similarity to that coding for Fe-containing superoxide dismutases (SodB). The R.
      capsulatus sodB gene was expressed in E. coli, and the nature of the metal ligand
      was confirmed by inhibitor sensitivity assays with lysates from both bacterial
      species. Activity staining of cleared Rhodobacter lysates resolved by
      polyacrylamide gel electrophoresis indicated that SodB was the only superoxide
      dismutase present in this phototrophic organism. The sodB gene was expressed at
      low levels in R. capsulatus cells grown under anaerobic or semiaerobic
      conditions, but expression was strongly induced upon exposure of the bacteria to
      air or to methyl viologen. Attempts to construct a sodB mutant in this organism
      by allelic exchange of the chromosomal copy of the gene with a suicide plasmid
      containing a mutated sodB gene were unsuccessful, strongly suggesting that the
      encoded superoxide dismutase is essential for viability of R. capsulatus in
      aerobic cultures.

PMID- 9765575
TI  - Novel rkp gene clusters of Sinorhizobium meliloti involved in capsular
      polysaccharide production and invasion of the symbiotic nodule: the rkpK gene
      encodes a UDP-glucose dehydrogenase.
AB  - The production of exopolysaccharide (EPS) was shown to be required for the
      infection process by rhizobia that induce the formation of indeterminate nodules
      on the roots of leguminous host plants. In Sinorhizobium meliloti (also known as
      Rhizobium meliloti) Rm41, a capsular polysaccharide (KPS) analogous to the group
      II K antigens of Escherichia coli can replace EPS during symbiotic nodule
      development and serve as an attachment site for the strain-specific bacteriophage
      phi16-3. The rkpA to -J genes in the chromosomal rkp-1 region code for proteins
      that are involved in the synthesis, modification, and transfer of an as-yet
      unknown lipophilic molecule which might function as a specific lipid carrier
      during KPS biosynthesis. Here we report that with a phage phi16-3-resistant
      population obtained after random Tn5 mutagenesis, we have identified novel
      mutants impaired in KPS production by genetic complementation and biochemical
      studies. The mutations represent two novel loci, designated the rkp-2 and rkp-3
      regions, which are required for the synthesis of rhizobial KPS. The rkp-2 region
      harbors two open reading frames (ORFs) organized in monocistronic transcription
      units. Although both genes are required for normal lipopolysaccharide production,
      only the second one, designated rkpK, is involved in the synthesis of KPS. We
      have demonstrated that RkpK possesses UDP-glucose dehydrogenase activity, while
      the protein product of ORF1 might function as a UDP-glucuronic acid epimerase.

PMID- 9765576
TI  - Different phenotypic classes of Sinorhizobium meliloti mutants defective in
      synthesis of K antigen.
AB  - For Sinorhizobium meliloti (also known as Rhizobium meliloti) AK631 to establish
      effective symbiosis with alfalfa, it must be able to synthesize a symbiotically
      active form of its K antigen, a capsular polysaccharide containing a Kdo (3-deoxy
      D-manno-octulosonic acid) derivative. Previously isolated mutants defective in
      the synthesis of K antigen are resistant to bacteriophage phi16-3. By screening
      ca. 100,000 Tn5-mutagenized R. meliloti bacteria for resistance to bacteriophage
      phi16-3, we isolated 119 mutants, 31 of which could not be complemented by genes
      previously identified as being required for K-antigen synthesis. Of these 31 new
      mutants, 13 were symbiotically defective and lacked the K antigen. Through
      genetic and phenotypic analyses, we have grouped these mutants into four distinct
      classes. Although all of these mutants lack the K antigen, many also have altered
      lipopolysaccharides (LPS), suggesting that the biochemical pathways for the
      synthesis of K antigen and LPS have common enzymatic steps. In addition, we have
      found that these and other classes of K-antigen-defective mutants of S. meliloti
      AK631 exhibit unique patterns of sensitivities to phage strains to which the
      parental strain was resistant. Our studies have identified new classes of genes
      required for both the synthesis of K antigen and the symbiotic proficiency of S.
      meliloti AK631. Some of these classes of genes also play a role in LPS synthesis.

PMID- 9765577
TI  - Point mutations in the integron integrase IntI1 that affect recombination and/or
      substrate recognition.
AB  - The site-specific recombinase IntI1 found in class 1 integrons catalyzes the
      excision and integration of mobile gene cassettes, especially antibiotic
      resistance gene cassettes, with a site-specific recombination system. The
      integron integrase belongs to the tyrosine recombinase (phage integrase) family.
      The members of this family, exemplified by the lambda integrase, do not share
      extensive amino acid identities, but three invariant residues are found within
      two regions, designated box I and box II. Two conserved residues are arginines,
      one located in box I and one in box II, while the other conserved residue is a
      tyrosine located at the C terminus of box II. We have analyzed the properties of
      IntI1 variants carrying point mutations at the three conserved residues of the
      family in in vivo recombination and in vitro substrate binding. We have made four
      proteins with mutations of the conserved box I arginine (R146) and three mutants
      with changes of the box II arginine (R280); of these, MBP-IntI1(R146K) and MBP
      IntI1(R280K) bind to the attI1 site in vitro, but only MBP-IntI1(R280K) is able
      to excise cassettes in vivo. However, the efficiency of recombination and DNA
      binding for MBP-IntI1(R280K) is lower than that obtained with the wild-type MBP
      IntI1. We have also made two proteins with mutations of the tyrosine residue
      (Y312), and both mutant proteins are similar to the wild-type fusion protein in
      their DNA-binding capacity but are unable to catalyze in vivo recombination.

PMID- 9765578
TI  - Influence of the MexAB-OprM multidrug efflux system on quorum sensing in
      Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa nalB mutants which hyperexpress the MexAB-OprM multidrug
      efflux system produce reduced levels of several extracellular virulence factors
      known to be regulated by quorum sensing. Such mutants also produce less acylated
      homoserine lactone autoinducer PAI-1, consistent with an observed reduction in
      lasI expression. These data suggest that PAI-1 is a substrate for MexAB-OprM, and
      its resulting exclusion from cells hyperexpressing MexAB-OprM limits PAI-1
      dependent activation of lasI and the virulence genes.

PMID- 9765580
TI  - Analysis of the novel benzylsuccinate synthase reaction for anaerobic toluene
      activation based on structural studies of the product.
AB  - Recent studies of anaerobic toluene catabolism have demonstrated a novel reaction
      for anaerobic hydrocarbon activation: the addition of the methyl carbon of
      toluene to fumarate to form benzylsuccinate. In vitro studies of the anaerobic
      benzylsuccinate synthase reaction indicate that the H atom abstracted from the
      toluene methyl group during addition to fumarate is retained in the succinyl
      moiety of benzylsuccinate. Based on structural studies of benzylsuccinate formed
      during anaerobic, in vitro assays with denitrifying, toluene-mineralizing strain
      T, we now report the following characteristics of the benzylsuccinate synthase
      reaction: (i) it is highly stereospecific, resulting in >95% formation of the (+)
      benzylsuccinic acid enantiomer [(R)-2-benzyl-3-carboxypropionic acid], and (ii)
      active benzylsuccinate synthase does not contain an abstracted methyl H atom from
      toluene at the beginning or at the end of a catalytic cycle.

PMID- 9765579
TI  - The 20S proteasome of Streptomyces coelicolor.
AB  - 20S proteasomes were purified from Streptomyces coelicolor A3(2) and shown to be
      built from one alpha-type subunit (PrcA) and one beta-type subunit (PrcB). The
      enzyme displayed chymotrypsin-like activity on synthetic substrates and was
      sensitive to peptide aldehyde and peptide vinyl sulfone inhibitors and to the
      Streptomyces metabolite lactacystin. Characterization of the structural genes
      revealed an operon-like gene organization (prcBA) similar to Rhodococcus and
      Mycobacterium spp. and showed that the beta subunit is encoded with a 53-amino
      acid propeptide which is removed during proteasome assembly. The upstream DNA
      region contains the conserved orf7 and an AAA ATPase gene (arc).

PMID- 9765581
TI  - Efficiency of the pTF-FC2 pas poison-antidote stability system in Escherichia
      coli is affected by the host strain, and antidote degradation requires the lon
      protease.
AB  - The stabilization of a test plasmid by the proteic, poison-antidote plasmid
      addiction system (pas) of plasmid pTF-FC2 was host strain dependent, with a 100
      fold increase in stability in Escherichia coli CSH50, a 2.5-fold increase in E.
      coli JM105, and no detectable stabilization in E. coli strains JM107 and JM109.
      The lethality of the PasB toxin was far higher in the E. coli strains in which
      the pas was most effective. Models for the way in which poison-antidote systems
      stabilize plasmids require that the antidote have a much higher rate of turnover
      than that of the toxin. A decrease in host cell death following plasmid loss from
      an E. coli lon mutant and a decrease in plasmid stability suggested that the Lon
      protease plays a role in the rate of turnover of PasA antidote.

PMID- 9765582
TI  - Autoregulation of the pTF-FC2 proteic poison-antidote plasmid addiction system
      (pas) is essential for plasmid stabilization.
AB  - The pasABC genes of the proteic plasmid addiction system of broad-host-range
      plasmid pTF-FC2 were autoregulated. The PasA antidote was able to repress the
      operon 25-fold on its own, and repression was increased to 100-fold when the PasB
      toxin was also present. Autoregulation appears to be an essential requirement for
      pas-mediated plasmid stabilization because when the pas genes were placed behind
      the isopropyl-beta-D-thiogalactopyranoside (IPTG)-regulated tac promoter, they
      were unable to stabilize a heterologous test plasmid.

PMID- 9765583
TI  - Demonstration that the TyrR protein and RNA polymerase complex formed at the
      divergent P3 promoter inhibits binding of RNA polymerase to the major promoter,
      P1, of the aroP gene of Escherichia coli.
AB  - In previous studies, we have identified three promoters (P1, P2, and P3) in the
      regulatory region of the Escherichia coli aroP gene (P. Wang, J. Yang, and A. J.
      Pittard, J. Bacteriol. 179:4206-4212, 1997). Both P1 and P2 can direct mRNA
      synthesis for aroP expression, whereas P3 is a divergent promoter which overlaps
      with P1. The repression of transcription from the major promoter, P1, has been
      postulated to involve the activation of the divergent promoter, P3, by the TyrR
      protein (P. Wang, J. Yang, B. Lawley, and A. J. Pittard, J. Bacteriol. 179:4213
      4218, 1997). In the present study, we confirmed the proposed mechanism of P3
      mediated repression of P1 transcription by studying the binding of RNA polymerase
      to the promoters P1 and P3 in vitro in the presence and absence of TyrR protein
      and its cofactors. Our results show that (i) only one RNA polymerase molecule can
      bind to the DNA fragment carrying the aroP regulatory region, (ii) RNA polymerase
      has a higher affinity for P1 than for either P2 or P3 and binds to P1 in the
      absence of TyrR protein, (iii) in the presence of TyrR protein and its cofactor,
      phenylalanine or tyrosine, RNA polymerase preferentially binds to P3, and (iv)
      RNA polymerase does not respond to the activation-defective mutant TyrR protein
      TyrR-RQ10 and remains bound to P1 in the presence of TyrR-RQ10 and either of the
      cofactors.

PMID- 9765584
TI  - Characterization of the mIHF gene of Mycobacterium smegmatis.
AB  - Integration of mycobacteriophage L5 requires the mycobacterial integration host
      factor (mIHF) in vitro. mIHF is a 105-residue heat-stable polypeptide that is not
      obviously related to HU or any other small DNA-binding proteins. mIHF is most
      abundant just prior to entry into stationary phase and is essential for the
      viability of Mycobacterium smegmatis.

PMID- 9765585
TI  - Gram-negative bacteria produce membrane vesicles which are capable of killing
      other bacteria.
AB  - Naturally produced membrane vesicles (MVs), isolated from 15 strains of gram
      negative bacteria (Citrobacter, Enterobacter, Escherichia, Klebsiella,
      Morganella, Proteus, Salmonella, and Shigella strains), lysed many gram-positive
      (including Mycobacterium) and gram-negative cultures. Peptidoglycan zymograms
      suggested that MVs contained peptidoglycan hydrolases, and electron microscopy
      revealed that the murein sacculi were digested, confirming a previous modus
      operandi (J. L. Kadurugamuwa and T. J. Beveridge, J. Bacteriol. 174:2767-2774,
      1996). MV-sensitive bacteria possessed A1alpha, A4alpha, A1gamma, A2alpha, and
      A4gamma peptidoglycan chemotypes, whereas A3alpha, A3beta, A3gamma, A4beta,
      B1alpha, and B1beta chemotypes were not affected. Pseudomonas aeruginosa PAO1
      vesicles possessed the most lytic activity.

PMID- 9765586
TI  - Relationship between spontaneous aminoglycoside resistance in Escherichia coli
      and a decrease in oligopeptide binding protein.
AB  - Changes in the amount of oligopeptide binding protein (OppA) in spontaneous
      kanamycin-resistant mutants of Escherichia coli were investigated. Among 20
      colonies obtained from 10(8) cells cultured in the presence of 20 microgram of
      kanamycin/ml, 1 colony had no detectable OppA and 7 colonies were mutants with
      reduced amounts of OppA. Sensitivity of wild-type cells to kanamycin increased
      slightly by transformation of the oppA gene, but the sensitivity of the mutants
      increased greatly by the transformation. A mutant with no OppA was found to be a
      nonsense mutant of the oppA gene at amino acid position 166. In a mutant having a
      reduced level of OppA, the reduction was due to the decrease in OppA synthesis at
      the translational level. These mutants were also resistant to other
      aminoglycoside antibiotics, including streptomycin, neomycin, and isepamicin.
      Isepamicin uptake activities decreased greatly in these two kinds of mutants. The
      results support the proposition that aminoglycoside antibiotics are transported
      into cells by the oligopeptide transport system, and that transport is an
      important factor for spontaneous resistance to aminoglycoside antibiotics.

PMID- 9765587
TI  - The nine genes of the Nocardia lactamdurans cephamycin cluster are transcribed
      into large mRNAs from three promoters, two of them located in a bidirectional
      promoter region.
AB  - The nine biosynthesis genes of the Nocardia lactamdurans cephamycin cluster are
      expressed as three different mRNAs initiating at promoters latp, cefDp, and
      pcbABp, as shown by low-resolution S1 nuclease protection assays and Northern
      blotting analysis. Bidirectional expression occurred from divergent promoters
      (latp and cefDp) located in a 629-bp intergenic region that contains three
      heptameric direct repeats similar to those recognized by members of the SARP
      (Streptomyces antibiotic regulatory proteins) family. The lat gene is transcribed
      in a single monocistronic transcript initiating at latp. A second unusually long
      polycistronic mRNA (more than 16 kb) corresponding to six biosynthesis genes
      (pcbAB, pcbC, cmcI, cmcJ, cefF, and cmcH) started at pcbABp. A third
      polycistronic mRNA corresponding to the cefD and cefE genes started at cefDp.

PMID- 9765588
TI  - A sequence based computational identification of a Drosophila developmentally
      regulated TATA-less RNA polymerase II promoter and its experimental validation.
AB  - Many RNA polymerase II promoters lack the characteristic TATA box sequence
      located -25/-30 nucleotides upstream from the transcription start. In Drosophila,
      half of the promoters identified so far are TATA-deficient. The yemanuclein-alpha
      gene whose promoter activity is restricted to oogenesis, falls in this class. A
      number of upstream and downstream promoter elements have been identified for some
      TATA-less promoters. The yem-alpha promoter contains none of the consensus
      elements identified so far. Our work was based on the assumption that the
      physical parameters of the DNA could be used to predict the location of the yem
      alpha promoter. A sequence based computational analysis allowed us to determine
      the characteristic changes of DNA curvature and helix stability in the
      presumptive regulatory region. Our experimental data were in good agreement with
      the computational analysis. We have started to investigate the general value of
      this approach by analyzing other promoters.

PMID- 9765589
TI  - The major APN transcript of the alveolar type II epithelial cell originates from
      a unique upstream promoter region.
AB  - Aminopeptidase N (APN, EC 3.4.11.2) is an ectopeptidase expressed in lung at the
      apical surface of alveolar type II epithelial cells. Its expression is
      upregulated during fetal lung development. To begin to understand the regulation
      of APN expression during lung development, we used the rapid modification of cDNA
      ends (RACE) to clone the 5' end of the major APN transcript in rat lung and
      alveolar type II cells. The cloned sequence revealed a unique 135 bp untranslated
      exon which genomic cloning and restriction mapping indicated was located more
      than 14 kb upstream from the coding sequence. A 172 bp genomic fragment flanking
      the untranslated exon produced a high level of expression of a reporter gene in
      transient transfection assays using a human lung adenocarcinoma cell line. The
      DNA fragment includes elements known to be important for expression of lung
      specific proteins, including the surfactant-associated proteins A, B, and C and
      the Clara cell specific protein. Comparison of the APN genomic sequences and gene
      structure from human and rat suggests that the exon present in the rat lung
      transcript may result from the use of a previously uncharacterized APN promoter.

PMID- 9765590
TI  - A putative lichenysin A synthetase operon in Bacillus licheniformis: initial
      characterization.
AB  - Certain Bacillus licheniformis strains isolated from oil wells have been shown to
      produce a very effective biosurfactant, lichenysin A, which is structurally
      similar to another less active lipopeptide, surfactin. Surfactin, like many small
      peptides in prokaryotes and lower eukaryotes, is synthesized non-ribosomally by
      multi-enzyme peptide synthetase complex. Analysis of several peptide synthetases
      of bacterial and fungal origin has revealed a high degree of sequence
      conservation. Two 35-mer oligonucleotides derived from highly conserved motifs
      ('core I' and 'core II') of surfactin synthetase were used to identify the cloned
      putative operon of lichenysin A synthetase lchA from B. licheniformis BNP29, a
      strain not amenable to genetic manipulation in a BAC system (F-plasmid-based
      bacterial artificial chromosome) based on Escherichia coli and its single-copy
      plasmid F-factor. A 32.4 kb fragment containing lichenysin A biosynthesis locus
      was sequenced and analysed. The structural architecture of putative lichenysin A
      synthetase protein containing seven amino acid (aa) activation-thiolation, two
      epimerization and one thioesterase domains is discussed in terms of its
      similarity to surfactin and other peptide synthetases. The 100 aa peptide chain
      situated between the highly conserved signature sequences FDXX and NXYGPTE(IV)X
      within amino acid binding domains of peptide synthetases is proposed to be a
      minimal block dictating the substrate specificity of the enzymes. A new operon
      type structure has been localized directly upstream from the lichenysin A
      synthetase genes which, on the basis of sequence determination, potentially
      encode a four-member ABC-type transport system involved in product secretion.

PMID- 9765591
TI  - Poly(ADP-ribose) binding properties of histone H1 variants.
AB  - Using a poly(ADP-ribose) binding assay on protein blots we examined the ability
      of rat testis histone H1 variants to establish non-covalent interactions with the
      polymer. All the H1 variants bound ADP-ribose polymers; the binding was salt
      resistant and highly specific, occurring even in the presence of a large excess
      of competitor DNA. A comparison among the H1 variants showed that H1t has the
      highest affinity for poly(ADP-ribose). Long and branched poly(ADP-ribose)
      molecules were found to be preferentially involved in the interaction with the
      histone variants. The results further corroborate the concept that non-covalent
      interactions of poly(ADP-ribose) with target proteins may constitute an important
      mechanism to modulate chromatin structure.

PMID- 9765592
TI  - A mutation in repB, the dictyostelium homolog of the human xeroderma pigmentosum
      B gene, has increased sensitivity to UV-light but normal morphogenesis.
AB  - Nucleotide excision repair (NER) is an important cellular defense mechanism which
      protects the integrity of the genome by removing DNA damage caused by UV-light or
      chemical agents. In humans, defects in the NER pathway result in the disease
      xeroderma pigmentosum (XP) which is characterized by increased UV-sensitivity,
      with increased propensity for skin cancer, and an array of developmental
      abnormalities. Some XP patients exhibit, in addition, symptoms of Cockayne's
      syndrome (CS) and trichothiodystrophy (TTD), which are characterized by increased
      UV-sensitivity, without increased cancer incidence, and an array of developmental
      abnormalities. Some NER genes, including the DNA helicases XPB and XPD, have been
      shown to function in transcription as well as repair, by virtue of being an
      integral part of the transcription initiation factor TFIIH. This dual function
      may account for the above-mentioned wide pleiotropy of phenotypes associated with
      defects in NER genes, and may explain why some XP patients exhibit developmental
      abnormalities in addition to XP symptoms. To date, only five XPB patients with
      three different mutations in the XPB gene have been reported. One of these
      mutations is a C to A transversion at the splice site at the beginning of the
      last exon, which resulted in a frameshift throughout the last exon. This patient
      shows combined clinical symptoms of XP and CS. The recent cloning of the repB
      gene, the Dictyostelium discoideum homolog of XPB, allowed us to generate a
      similar C-terminal mutation in the Dictyostelium, in order to test whether the
      defect in this NER gene has an effect on growth or development. To this end, we
      have constructed a C-terminal deletion repB mutant in Dictyostelium. To avoid the
      possibility that a null mutant would be lethal, we used direct homologous
      recombination to create a 46 amino acid C-terminal deletion mutant. Indeed, we
      were unable to obtain mutants with a longer 95 amino acid deletion. The repB
      delta C46 mutants showed an increased sensitivity to UV-light, but a normal
      pattern of UV-induced expression of repair genes, and no immediately obvious
      defect in either growth rate or development. The results suggest that the
      associated developmental defects in the human XPB patients may be due to
      mutations in another gene.

PMID- 9765593
TI  - Cloning, expression, characterization and role of the leader sequence of a lipase
      from Rhizopus oryzae.
AB  - A lipase from Rhizopus oryzae DSM 853 (ROL) was cloned from a chromosomal gene
      bank, sequenced and overexpressed in Escherichia coli. ROL and its precursors
      ProROL and PreProROL were purified and their pH and temperature profile was
      determined. In contrast to ROL, ProROL and PreProROL had considerably higher
      thermostability and a slightly higher pH optimum. Moreover, it could be
      demonstrated by in vitro experiments that the natural leader sequence of ROL is
      able to inhibit the folding supporting properties of the prosequence, resulting
      in a retardation of folding. In addition, there is strong evidence that all
      different lipase forms derived from Rhizopus sp. described in the literature are
      a result of different proteolytic processing and originate from the same gene.

PMID- 9765594
TI  - Binding and activation of the human aldehyde dehydrogenase 2 promoter by
      hepatocyte nuclear factor 4.
AB  - Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is expressed in a tissue-specific
      fashion with high levels in liver, heart, kidney, and muscle, and low levels in
      most other tissues. The ALDH2 promoter was found to bind nuclear proteins at a
      pair of adjacent sites approximately 300 bp upstream from the translation start
      site, each of which was contacted at motifs containing the hexamer A/GGGTCA. The
      3' site was shown to bind in vitro translated HNF-4. It was also shown by
      electrophoretic mobility shift assay utilizing antibodies against nuclear factors
      and rat liver nuclear extracts to be bound by hepatocyte nuclear factor 4 (HNF
      4), chicken ovalbumin upstream promoter transcription factor I and II, and
      retinoid X receptors. A reporter construct containing four copies of this
      promoter element was activated by co-transfection of an HNF-4 expression plasmid
      in COS-1 and hepatoma cell lines. These results suggest that the tissue
      specificity of ALDH2 expression is in part determined by its activation by HNF-4.

PMID- 9765595
TI  - Identification and characterization of the human adipocyte apM-1 promoter.
AB  - The human adipocyte-specific apM-1 gene encodes a secretory protein of the
      adipose tissue and seems to play a role in the pathogenesis of obesity. A 1.3 kb
      amount of the proximal promoter region has been cloned and analyzed for the
      presence of putative transcription factor binding sites. Several binding sites
      known to be involved in adipogenesis and regulation of adipocyte-specific genes
      (C/EBP, SREBP) are present. No TATA box, but a classical CCAAT box could be
      identified. To confirm functionality and cell specificity of the 1.3 kb promoter,
      a series of 5'-deleted fragments were ligated in front of the luciferase gene and
      the constructs were transfected into 3T3-L1 adipocytes. The reporter gene was
      effectively transcribed, as demonstrated by the expression of enzyme activity.
      The 5'-end of the human cDNA was completed by 5'-RACE-PCR. Several alternative
      transcription start sites were detected by RNase protection assay and primer
      extension analysis. In addition, an exon/intron boundary was mapped at the
      extreme 5'-end of the cDNA sequence. Genomic Southern blotting suggests that the
      human apM-1 gene is a single copy gene.

PMID- 9765596
TI  - Sequence and expression levels in human tissues of a new member of the aldo-keto
      reductase family.
AB  - We have isolated a human cDNA clone from small intestine that represents a new
      member of the aldo-keto reductase family. This new member showed 70% identity at
      the protein level to human aldose reductase and around 80% identity to other
      Chinese hamster and mouse reductases. The expression pattern shows that this
      message is located primarily in the adrenal gland, thus suggesting an involvement
      in steroid metabolism. It is also strongly expressed in the intestinal tract and
      has been called human small intestine reductase.

PMID- 9765597
TI  - The homeobox gene NTH23 of tobacco is expressed in the basal region of leaf
      primordia.
AB  - We reported isolation and characterization of a homeobox gene from tobacco,
      NTH23. The homeodomain structure of NTH23 was highly homologous to the same
      regions of class 2 genes of the KN1-type homeobox (sharing more than 85% amino
      acid identity), but was less similar to class 1 genes of KN1-type. RNA gel blot
      analysis revealed that NTH23 was expressed in all organs we tested although the
      gene is primarily expressed in young leaves. To determine more precisely the
      spatial expression pattern of NTH23 in tobacco, a chimeric NTH23::GUS fusion gene
      was introduced into tobacco. The signal of GUS activity was observed at the basal
      part of leaf blade primordia in the NTH23::GUS transgenic tobacco plants. This
      observation suggests the possibility that NTH23 may be important for the lateral
      growth of leaf blades.

PMID- 9765598
TI  - Human MAFA has alternatively spliced variants.
AB  - Human mast cell function-associated antigen (MAFA) cDNA has been cloned. This
      molecule is similar to the rat form having an intracellular domain containing a
      putative immunoreceptor tyrosine inhibition motif and an extracellular C type
      lectin-like domain. However, in contrast to rat MAFA, the amino acid sequence
      suggests the presence of two additional extracellular N-linked glycosylation
      sites. In addition, alternative mRNA transcripts are observed that differ
      substantially from those found in the rat.

PMID- 9765599
TI  - Molecular cloning and characterization of the Plasmodium falciparum cytidine
      triphosphate synthetase gene.
AB  - Using degenerate oligonucleotides derived from conserved amino acid regions of
      cytidine triphosphate synthetase, a fragment of the gene from the malarial
      parasite, Plasmodium falciparum, was isolated by polymerase chain reaction (PCR).
      This fragment was used as a probe in the isolation of genomic clones containing
      the entire pfCTP synthetase coding region (2580 bp). The gene encodes the largest
      CTP synthetase found in any organism to date due to the presence of two
      additional sequences which are part of the continuous open reading frame and are
      not introns as their presence in the mRNA was confirmed by reverse transcriptase
      PCR. These features distinguish the parasite enzyme from that of the host making
      it an attractive target for structure based drug design.

PMID- 9765600
TI  - Cloning of the cDNA for glutamyl-tRNA synthetase from Arabidopsis thaliana.
AB  - We cloned and characterized a full-length cDNA that encodes a glutamyl-tRNA
      synthetase (GluRSAt) from Arabidopsis. The GluRSAt is coded by a single gene. A
      transcript of about 2.3 kb hybridized with the cDNA. The deduced protein from the
      cDNA contained 719 amino acids with an estimated molecular mass of 81 kDa.
      Expression of the GluRSAt in E. coli resulted in a protein of the expected size.
      Comparison of the amino acid sequence GluRSAt to other glutamyl-tRNA synthetases
      showed strong sequence similarity to cytoplasmic GluRS proteins.

PMID- 9765601
TI  - cDNA cloning and expression of a novel serine protease, TLSP.
AB  - A cDNA for a putative novel serine protease, TLSP, was cloned from human
      hippocampus cDNA with polymerase chain reaction based strategies. The putative
      amino acid sequence of TLSP is similar to the trypsin-type serine proteases. TLSP
      mRNA is expressed in keratinocytes. Overexpressed TLSP protein in neuro2a cells
      was detected in culture medium.

PMID- 9765604
TI  - [AIDS drug in the correct form].

PMID- 9765603
TI  - Cloning of a novel testis specific protein serine/threonine phosphatase, PPN 58A,
      from Drosophila melanogaster.
AB  - A gene encoding a novel member of the PPP family of protein serine/threonine
      phosphatases, termed PPN 58A, was cloned from Drosophila melanogaster. The
      deduced amino acid sequence of PPN 58A exhibits 59-62% identity to D.
      melanogaster PP1 isoforms, 51% identity to D. melanogaster PPY 55A and < or = 40%
      identity to other members of the PPP family. The single copy gene PPN 58A maps to
      chromosome 2 locus 58A. Analysis of PPN 58A mRNA reveals that, like PPY 55A, PPN
      58A is a testis specific enzyme.

PMID- 9765602
TI  - Four distinct regions in the auxiliary domain of heterogeneous nuclear
      ribonucleoprotein C-related proteins.
AB  - A 306 amino acid sequence deduced from a rabbit bladder cDNA is 98% identical to
      the human heterogeneous nuclear ribonucleoprotein (hnRNP) C2. The sequence
      comparison of the hnRNP C-related proteins reveals four distinct regions in the C
      terminal auxiliary domain. The region next to the N-terminal RNA-binding domain
      is variable in length. Following the variable region, a basic region and a
      leucine zipper are conserved in all hnRNP C-related proteins including mouse and
      human Raly. Several Lys-Ser-Gly repeats are present in the basic region of the
      hnRNP C proteins. The C-terminal region is more divergent between hnRNP C and
      Raly. Signature sequences and possible functions are proposed for the different
      regions of the hnRNP C proteins.

PMID- 9765605
TI  - [International interhospital transfer by scheduled airline].
AB  - BACKGROUND AND OBJECTIVE: International long-distance travel increasingly takes
      elderly and sometimes already ill persons to foreign countries. In case of
      illness it is usually best, for both medical and social reasons, that the person
      return home. This study was undertaken to assess possibilities and limits of
      bringing such patients home by scheduled airline. PATIENT AND METHODS: The
      transportation reports and case notes of 95 patients who had been repatriated to
      Germany in 1995 and 1996 for medical reasons were analysed retrospectively. The
      mean age was 56 (16-94) years. 50% of the patients had medical, 23% surgical, 19%
      neurological and 8% psychiatric illnesses. RESULTS: None of the patients died
      during transport. The NACA score (National Advisory Committee for Aeronautics,
      USA) for determining the degree of severity of an illness (point scale 1-7) in
      this group of patients was between 1 and 4, median of 3. Five patients with a
      score of 5 or higher were judged not to be fit for transport. Two were
      repatriated by ambulance plane, in three transport was postponed by a few days.
      No invasive procedures, other than providing intravenous access, were necessary.
      CONCLUSIONS: Patients who fall ill abroad can be safely and carefully brought
      home by scheduled airliner over great distances without additional risk caused by
      the transport. Ambulance planes are needed only in illnesses with an NACA score
      of 4 or higher.

PMID- 9765606
TI  - [Angina pectoris in "coronary steal syndrome" caused by a coronary fistula in the
      left ventricle].
AB  - HISTORY AND CLINICAL FINDINGS: A 55-year-old female patient reported left-sided
      chest pain at rest as well as during exercise, which recurred during the last
      three years before admission. Cardiovascular risk factors included
      hypercholesterolemia and smoking. The physical examination of the patient was
      unremarkable. INVESTIGATIONS: The ECG at rest showed T-wave inversions in leads
      I, aVL, V3-V6 and ergometric exercise testing resulted in angina pectoris and
      descending ST-segments in leads V3-V6. Stress thallium 201 scintigraphy
      demonstrated a reversible perfusion deficit of the the anterior wall at peak
      exercise. The left ventricular angiogram and echocardiogram revealed normal end
      diastolic dimensions and regular systolic contractions without signs of left
      ventricular hypertrophy. Selective coronary arteriography excluded
      hemodynamically relevant stenosis of the coronary arteries. A coronary artery
      fistula originating from a large, ectatic first diagonal branch with drainage
      into the left ventricle was observed. TREATMENT AND COURSE: Because the patient
      rejected interventional therapy she was treated conservatively and follow-up
      investigations 3 and 4 years after arteriography revealed unchanged clinical
      symptomatology. CONCLUSION: In this case a "coronary steal" phenomenon caused by
      the coronary fistula induced myocardial ischemia. Therefore if present congenital
      coronary anomalies have to be considered in patients with chest pain and normal
      coronary angiogram.

PMID- 9765607
TI  - [Meningeal irritation--a complication of herpes zoster].
AB  - HISTORY AND CLINICAL FINDINGS: A previously healthy 26-year-old man complained of
      gradually increasing headache after an attack of flu. After 4 days an erythema
      with papules but no blisters was noted in the area of distribution of the left
      10th thoracic nerve. As a child he had varicella (chickenpox) without
      complications. INVESTIGATIONS: Lymphocytic pleocytosis and evidence of an
      abnormal blood-brain barrier were noted in cerebrospinal fluid (CSF). Serology
      for varicella zoster virus revealed an IgG titre of > 7400 IU/l in serum and 21
      IU/l in CSF. The corresponding IgM titres were negative. TREATMENT AND COURSE:
      The headaches and cutaneous changes regressed under i.v. treatment with
      acyclovir, 10 mg/kg body weight, 3 x daily for 10 days. Repeat CSF examination
      after 10 days showed merely minimal residual changes of inflammation. CONCLUSION:
      This case illustrates the risk of severe neurological complications of herpes
      zoster infection. A seemingly minor rash with headache must be correctly
      diagnosed and immediate high-dosage acyclovir treatment instituted to prevent
      life-threatening and severe complications of herpes zoster meningitis or
      encephalitis.

PMID- 9765608
TI  - [Therapy of vertigo].

PMID- 9765609
TI  - [Ten years of coronary stenting--current status and perspectives].

PMID- 9765610
TI  - [Longterm manometry in patients with chest pain of undetermined cause. Which
      parameters should be evaluated and why?].

PMID- 9765611
TI  - [Diagnosis of chronic hepatitis].

PMID- 9765612
TI  - [The path to "Doctor of Medicine"--how do doctoral candidates evaluate their
      dissertation?].

PMID- 9765613
TI  - Mortality and cancer incidence in Misasa, Japan, a spa area with elevated radon
      levels.
AB  - A historical cohort study was conducted in Misasa town, Tottori prefecture,
      Japan, where radon spas have been operating for a long time. Misasa town was
      divided into an elevated radon level area and a control area, with mean indoor
      radon levels of about 60 and 20 Bq/m3, respectively. In total, 3,083 subjects in
      the elevated radon level area and 1,248 in the control area, all aged 40 or older
      on January 1, 1976, were followed up until December 31, 1993, for a mean period
      of 14 years. The mortality rates from all causes exhibited no difference between
      the elevated radon level area and the control area for both sexes. No difference
      was observed in the incidence of all-site cancers (age, period-adjusted rate
      ratios by Poisson regression, RR = 1.06, 95% confidence interval (CI) 0.79-1.42
      for males, RR = 0.90, 95% CI 0.65-1.24 for females), while stomach cancer
      incidence seemed to decrease for both sexes (RR = 0.70, 95% CI 0.44-1.11 for
      male, RR = 0.58, 95% CI 0.34-1.00 for female) and lung cancer incidence for males
      only seemed to increase (RR = 1.65, 95% CI 0.83-3.30 for male, RR = 1.07, 95% CI
      0.28-4.14 for female) in the elevated radon level area. Caution is needed in the
      interpretation of these findings, however, since the individual exposure level
      was not measured and major confounding factors, such as smoking and diet, could
      not be controlled in this study.

PMID- 9765614
TI  - Human T-lymphotropic virus type-I infection, antibody titers and cause-specific
      mortality among atomic-bomb survivors.
AB  - There have been few longitudinal studies on the long-term health effects of human
      T-lymphotropic virus type-I (HTLV-I) infection. The authors performed a cohort
      study of HTLV-I infection and cause-specific mortality in 3,090 atomic-bomb
      survivors in Nagasaki, Japan, who were followed from 1985-1987 to 1995. The
      prevalence of HTLV-I seropositivity in men and women was 99/1,196 (8.3%) and
      171/1,894 (9.0%), respectively. During a median follow-up of 8.9 years, 448
      deaths occurred. There was one nonfatal case of adult T-cell leukemia/lymphoma
      (incidence rate = 0.46 cases/1,000 person-years; 95% confidence interval [CI]
      0.01-2.6). After adjustment for sex, age and other potential confounders,
      significantly increased risk among HTLV-I carriers was observed for deaths from
      all causes (rate ratio [RR] = 1.41), all cancers (RR = 1.64), liver cancer (RR =
      3.04), and heart diseases (RR = 2.22). The association of anti-HTLV-I
      seropositivity with mortality from all non-neoplastic diseases (RR = 1.40) and
      chronic liver diseases (RR = 5.03) was of borderline significance. Possible
      confounding by blood transfusions and hepatitis C/B (HCV/HBV) viral infections
      could not be precluded in this study. However, even after liver cancer and
      chronic liver diseases were excluded, mortality rate was still increased among
      HTLV-I carriers (RR = 1.32, 95% CI 0.99-1.78), especially among those with high
      antibody titers (RR = 1.56, 95% CI 0.99-2.46, P for trend = 0.04). These findings
      may support the idea that HTLV-I infection exerts adverse effects on mortality
      from causes other than adult T-cell leukemia/lymphoma. Further studies on
      confounding by HCV/HBV infections and the interaction between HCV/HBV and HTLV-I
      may be required to analyze the increased mortality from liver cancer and chronic
      liver diseases.

PMID- 9765615
TI  - Different responses other than the formation of DNA-adducts between the livers of
      carcinogen-resistant rats (DRH) and carcinogen-sensitive rats (Donryu) to 3'
      methyl-4-dimethylaminoazobenzene administration.
AB  - Carcinogen-resistant inbred DRH rats developed from the Donryu strain showed a
      remarkably low incidence of liver tumors when they were fed diets containing
      hepatocarcinogens such as 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). In
      this work, we examined various characteristics of male DRH and Donryu rats during
      3'-Me-DAB administration for 8 weeks. 32P-Postlabeling analysis showed that
      essentially similar levels of DNA-adducts were generated by the metabolites of 3'
      Me-DAB in the livers of these two strains of rats at several time points.
      However, both GADD45 (growth arrest and DNA damage-inducible) and O6
      methylguanine methyltransferase (putatively DNA damage-inducible) mRNA levels
      were increased significantly in Donryu rat livers, but were increased to a lesser
      extent in DRH rats. [3H]Thymidine incorporation into hepatic DNA began to
      increase around 10 to 20 days after the start of 3'-Me-DAB administration in
      Donryu rats probably due to DNA repair, while no significant change occurred in
      DRH rats under the same conditions. Furthermore, inductions of heme oxygenase
      (due to degradation of heme-proteins) and hepatocyte growth factor (HGF; cell
      death and regeneration of hepatocytes) mRNAs were greater in Donryu rat livers
      than those of DRH, suggesting that the former were more sensitive to cytotoxic
      effects of 3'-Me-DAB than the latter. Another remarkable difference observed
      between these two strains was the significant induction of cytochrome P-450 2E1
      mRNA in Donryu rat livers; this may contribute to the generation of reactive
      oxygen intermediates. Finally, increases of glutathione S-transferase (P-form)
      and gamma-glutamyltranspeptidase mRNAs as marker enzymes of preneoplastic changes
      of hepatocytes were clearly seen only in Donryu rat livers at 6 to 8 weeks after
      the start of 3'-Me-DAB administration. These results indicate that the different
      susceptibility to hepatocarcinogenesis between these two strains of rats may
      arise from events other than the DNA adduct formation.

PMID- 9765617
TI  - Mutation analysis of the WT1 gene in myelodysplastic syndromes.
AB  - The WT1 tumor suppressor gene was examined for mutations in a panel of 44
      patients with myelodysplastic syndromes (MDS) including acute myelogenous
      leukemias (AML) secondary to MDS, using polymerase chain reaction single-strand
      conformation polymorphism (PCR-SSCP) analysis and sequencing analysis. A WT1
      mutation was detected in one out of 17 cases of AML secondary to MDS. This
      mutation exists upstream of the zinc finger region and is predicted to produce a
      truncated WT1 protein lacking the zinc finger region. No mutations were detected
      in 27 MDS patients who had not progressed to AML. This is the first report of
      analysis for WT1 mutations in a large number of MDS patients, suggesting that WT1
      mutations are uncommon in MDS. Abnormalities in this gene may, however,
      contribute to a small proportion of cases showing progression from MDS into AML.

PMID- 9765616
TI  - Development of high-grade renal cell carcinomas in rats independently of somatic
      mutations in the Tsc2 and VHL tumor suppressor genes.
AB  - Ferric nitrilotriacetate (Fe-NTA) induces renal proximal tubular damage that
      ultimately leads to a high incidence of renal cell carcinoma (RCC) in rats. The
      RCCs are characterized by 1) high incidence of pulmonary metastasis and
      peritoneal invasion, 2) high incidence of tumor-associated mortality and 3)
      possible involvement of reactive oxygen species in carcinogenesis. The present
      study investigated the possible role of Tsc2 and VHL tumor suppressor genes in
      this model. Thirty-four Fe-NTA-induced primary RCCs and 20 other primary or
      metastatic tumors of rats were searched for genetic alteration in all the coding
      exons of both genes by polymerase chain reaction-single-strand-conformation
      polymorphism analysis and sequencing in conjunction with morphological
      evaluation. In the Fe-NTA-induced RCCs, frequency of metastasis or invasion was
      proportionally associated with the nuclear grade of the tumor (grades 1-3). Only
      one Fe-NTA-induced RCC of grade 1 revealed missense mutations with loss of
      heterozygosity in exon 10 of the Tsc2 gene (codons 334, GTG (Val) to GCG (Ala),
      and 336, TAT (Tyr) to CAT (His). No mutation was found in the VHL gene. The
      results suggest that 1) high-grade RCCs can develop in the absence of mutations
      in the Tsc2 and VHL genes in rats, and that 2) Tsc2 gene somatic mutation can
      nonetheless be one of the causes of non-Eker rat RCCs.

PMID- 9765618
TI  - Infrequent mutations of the hOGG1 gene, that is involved in the excision of 8
      hydroxyguanine in damaged DNA, in human gastric cancer.
AB  - DNA glycosylase, encoded by the hOGG1 gene, repairs 8-hydroxyguanine (oh8Gua),
      which is an oxidatively damaged mutagenic base. To clarify whether the DNA repair
      activity of hOGG1 protein is involved in gastric carcinogenesis, we examined 9
      gastric cancer cell lines and 35 primary gastric cancers for mutations and
      genetic polymorphisms of the hOGG1 gene by polymerase chain reaction-single
      strand conformation polymorphism analysis. A G-to-A transition was detected in a
      gastric cancer cell line, MKN1. This nucleotide change caused the conversion of
      the amino acid from Arg to His at codon 154, which is located in a domain highly
      conserved among human, mouse, and yeast OGG1 proteins. No mutation was detected
      in primary gastric cancers. We compared the distribution of the polymorphic
      alleles associated with enzymatic activity (hOGG1-Ser326 vs. hOGG1-Cys326)
      between 35 gastric cancer patients and 42 healthy individuals. Although the
      frequency of the Cys326 allele, associated with low enzymatic activity, in
      gastric cancer patients was a little higher than that in healthy individuals, the
      difference did not reach statistical significance. These results suggest that low
      hOGG1 activity due to mutations and genetic polymorphisms is involved in the
      development of only a small subset of gastric cancers.

PMID- 9765619
TI  - Expression of cadherin-catenin cell adhesion molecules, phosphorylated tyrosine
      residues and growth factor receptor-tyrosine kinases in gastric cancers.
AB  - Tyrosine phosphorylation of beta-catenin, an intracytoplasmic E-cadherin-binding
      protein, has been shown to disrupt the cadherin-mediated cell adhesion system in
      vitro. In order to investigate the relationships of expression and tyrosine
      phosphorylation of cadherin-catenin molecules and expression of growth factor
      receptor-tyrosine kinase with loose cell-to-cell adhesion, immunohistochemical
      staining for E-cadherin, alpha- and beta-catenin, phosphorylated tyrosine
      residues and tyrosine kinase receptors, including c-erbB-2, epidermal growth
      factor-receptor (EGF-R), c-met and K-sam, in 17 undifferentiated- and 10
      differentiated-type human gastric cancers was performed. Loss or reduced
      expressions of E-cadherin and alpha- and beta-catenin (11, 11, 10 cancers,
      respectively) were observed in the former, but not the latter. Diffuse
      cytoplasmic staining of E-cadherin, alpha- and beta-catenin and phosphotyrosine
      residues was observed frequently in the undifferentiated-type cancers. The
      cytoplasmic localization of phosphotyrosine residues in undifferentiated-type
      cancers was correlated significantly with K-sam expression (P < 0.01) and diffuse
      cytoplasmic staining of E-cadherin (P < 0.05) and beta-catenin (P < 0.05).
      Expression of K-sam protein was detected significantly more frequently in
      undifferentiated- (6/17; P < 0.05) than differentiated-type adenocarcinomas
      whereas the converse applied to c-erbB-2 expression (8/10 of the latter, P <
      0.05). Tyrosine phosphorylation of beta-catenin was directly confirmed in the
      protein extracts of one undifferentiated-type gastric cancer. These data indicate
      that alteration of tyrosine phosphorylation status associated with K-sam
      expression may cause the cytoplasmic distribution of cadherin-catenin molecules
      and loose cell-cell adhesion in undifferentiated-type gastric cancers.

PMID- 9765620
TI  - Nonsense mutation at codon 63 of the BRCA1 gene in Japanese breast cancer
      patients.
AB  - The involvement of abnormalities of the BRCA1 gene in breast cancers in Japanese
      patients without any family history of this cancer was investigated by polymerase
      chain reaction-based single-strand conformation polymorphism analysis of the DNA
      sequences corresponding to the zinc finger domain (exons 2, 3 and 5) and the
      binding domain with Rad51 (exon 11) of the BRCA1 protein. An identical nonsense
      mutation at codon 63 (TTA to TAA) was found in 2 of 56 (3.5%) breast cancers from
      independent patients. The nucleotide change was also detected in the DNAs from
      non-cancerous tissues of both patients and therefore was a germline mutation. One
      of the patients was a member of a pedigree involving 3 ovarian cancer and 1
      gastric cancer patients, while the other patient had no family history of
      malignancy. The same germline mutation at codon 63 was reported in four other
      independent Japanese pedigrees with frequent breast cancer, but not in such
      families in other countries. These observations suggest that the mutation
      commonly originated from a single Japanese ancestor. No other mutation of the
      BRCA1 gene was observed in the samples analyzed in this study. A low incidence of
      germline mutation and the absence of somatic mutation suggest that the aberration
      of the BRCA1 gene is involved only in a subset of Japanese breast cancers.

PMID- 9765621
TI  - Somatic mutations of the PTEN/MMAC1 gene in fifteen Japanese endometrial cancers:
      evidence for inactivation of both alleles.
AB  - Loss of heterozygosity (LOH) of chromosome 10q is observed in approximately 40%
      of endometrial cancers. Mutations in PTEN/MMAC1, a gene recently isolated from
      the 10q23 region, are responsible for two dominantly inherited neoplastic
      syndromes, Cowden disease and Bannayan-Zonana syndrome. Somatic mutations of this
      gene have also been detected in sporadic cancers of the brain, prostate and
      breast. To investigate the potential role of this putative tumor suppressor gene
      in endometrial carcinogenesis as well, we examined 46 primary endometrial cancers
      for LOH at the 10q23 region, and for mutations in the entire coding region and
      exon-intron boundaries of the PTEN/MMAC1 gene. LOH was identified in half of the
      38 informative cases, and subtle somatic mutations were detected in 15 tumors
      (33%). Our results suggest that of the genes studied so far in endometrial
      carcinomas, PTEN/MMAC1 is the most commonly mutated one, and that inactivation of
      both copies by allelic loss and/or mutation, a pattern that defines genes as
      "tumor suppressors," contributes to tumorigenesis in endometrial cancers.

PMID- 9765622
TI  - Sequence analysis of genes encoding rodent homologues of the human tumor
      rejection antigen SART-1.
AB  - Human SART-1 (hSART-1) gene encodes a 125 kD protein with a leucine-zipper motif
      expressed in the nucleus of all proliferating cells, and a 43 kD protein
      expressed in the cytosol of most epithelial cancers. In this study, two rodent
      genes (rSART-1 and mSART-1) homologous to hSART-1 were cloned from cDNA libraries
      of murine brain and a rat tumor cell line, respectively. mSART-1 and rSART-1 were
      highly homologous to hSART-1 with 86% and 84% identity at the nucleotide level,
      and 95% and 91% at the protein level, respectively. The leucine zipper domain and
      two basic amino acid portions that bind DNA, as well as peptide sequences
      recognized by human cytotoxic T lymphocytes (CTLs), were all conserved in these
      rodent genes. Nuclear protein homologous to the 125 kD hSART-1(800) protein, but
      not to the 43 kD cytosol SART-1(259) protein, was detectable with specific
      antibody in the nuclear fractions of rodent tumor cell lines, and normal rodent
      fetal liver and testis. These rodent genes should be a novel tool for studies on
      the biological roles of the SART-1 gene, and also in the construction of animal
      models of specific immunotherapy using SART-1 gene products.

PMID- 9765623
TI  - Differential expression of DNA topoisomerase II alpha and II beta genes between
      small cell and non-small cell lung cancer.
AB  - DNA topoisomerase II (Topo II) inhibitors are widely used in lung cancer
      chemotherapy, but small cell lung cancer (SCLC) and non-small cell lung cancer
      (NSCLC) show different sensitivity to them. In this study, we examined the gene
      expression levels of both isoforms of Topo II (II alpha and II beta) in lung
      cancer specimens to investigate the differential expression between SCLC and
      NSCLC. The expression levels of the Topo II alpha and Topo II beta genes were
      assessed in 80 autopsy samples (40 primary tumors and 40 corresponding normal
      lung tissues) by using the reverse transcription polymerase chain reaction. We
      found that the expression levels of the Topo II alpha gene in tumors were
      significantly higher than those in normal lung tissues, and that those in SCLC
      were significantly higher than those in NSCLC. There were no significant
      differences in Topo II beta gene expression between tumors and normal lung
      tissues and between SCLC and NSCLC. Further-more, correlation analysis revealed
      that Topo II alpha expression was correlated with Topo II beta expression in both
      tumor and normal lung tissues. These results indicate that a difference exists in
      the regulation of the Topo II gene between lung tumors and normal lung tissues.
      Our finding of differential expression of Topo II alpha between SCLC and NSCLC
      also suggests that the Topo II alpha expression level is associated with
      sensitivity to Topo II inhibitors.

PMID- 9765624
TI  - The TdT-mediated dUTP nick end labeling assay precisely assesses the DNA damage
      in human tumor xenografts.
AB  - Cultured HL-60, HeLa S3 and WiDr cells grown in male BALB/c nu/nu mice were
      studied by conventional and field-inversion DNA gel electrophoresis (FIGE), as
      well as by means of cytomorphological approaches, including TdT-mediated dUTP
      nick end labeling (TUNEL) assay. Chemosensitivity tests revealed HL-60 to be
      sensitive to vindesine (VDS), and HeLa S3 and WiDr to mitomycin C (MMC). Although
      VDS-treated HL-60 exhibited condensation of chromatin and a DNA ladder, MMC
      exposed HL-60 cells showed apoptotic figures without typical DNA ladders. With
      MMC-treated WiDr cells, neither DNA ladders nor apoptotic figures were observed.
      Cells characterized by chromatin condensation were TUNEL-positive in both treated
      and untreated cases with the exception of the MMC-treated WiDr case, in which
      many TUNEL-positive cells were observed without cytomorphological changes. On
      FIGE, DNA fragments of approximately 50, 300 and 400 kbp were detected in groups
      treated with both effective and ineffective drugs, as well as in untreated
      controls. Furthermore, change of the time parameters in FIGE resulted in
      different sizes (550 and 850 kbp) of DNA fragments. These findings indicate that
      i) cell death is not always detectable in terms of apoptotic figures or DNA
      oligonucleosomal fragmentation, ii) only the TUNEL assay is a reliable tool to
      detect DNA damage and, iii) FIGE does not provide accurate size profiles of
      macromolecular DNA fragments.

PMID- 9765626
TI  - Renal tumours: the new order.

PMID- 9765625
TI  - Rhenium-186-mercaptoacetyltriglycine-labeled monoclonal antibody for
      radioimmunotherapy: in vitro assessment, in vivo kinetics and dosimetry in tumor
      bearing nude mice.
AB  - Stability and immunoreactivity of 186Re-labeled monoclonal antibody were
      examined, and its in vivo kinetics was investigated in tumor-bearing Balb/c nu/nu
      female mice to assess the feasibility of using it in radioimmunotherapy (RIT). A
      murine IgG1, A7, against a 45 kD glycoprotein in human colon cancer was
      radiolabeled with 186Re by using a chelating method with a
      mercaptoacetyltriglycine (MAG3). 186Re-MAG3 complex was conjugated to A7 after
      esterification of 186Re-MAG3 with tetrafluorophenol (TFP). The efficiency of
      186Re-MAG3-TFP production and the labeling efficiency of A7 were 51-59% and 57
      60%, respectively. Immunoreactivity of purified 186Re-MAG3-A7 was 68.2% at
      infinite antigen excess. In 0.9% NaCl at 4 degrees C, the radioactivity (12.7
      MBq/mg, 3.55 MBq/ml) dissociated with time from 186Re-MAG3-A7 as a small
      molecular weight moiety because of autoradiolysis. The addition of ascorbic acid,
      5 mg/ml, as a radioprotectant or storage at -80 degrees C could effectively
      prevent the radiolysis of 186Re-MAG3-A7 for 7 days. Immunoreactivity of 186Re
      MAG3-A7, 6.70 MBq/mg (6.66 MBq/ml), stored in the presence of ascorbic acid was
      well retained up to 8 days after the preparation. In colon cancer xenografted
      mice, 31.0% of the injected dose/g of 186Re-MAG3-A7 had accumulated in the tumors
      at 24 h postinjection. Estimated radiation dose to tumors was 14.9 cGy/37 kBq up
      to 8 days postinjection which was 12-fold greater than the whole-body radiation
      dose. These in vivo characteristics were superior to those of A7 labeled with
      radioiodine, affording greater therapeutic ratios than 131I-A7. Because of the
      better image quality of 186Re-MAG3-A7 as well as more favorable dosimetry, 186Re
      MAG3-A7 would be a better choice for RIT of colon cancer than 131I-A7. These
      results indicated the feasibility of RIT with 186Re-MAG3-A7, though the
      prevention of radiolysis of the labeled antibody should be considered.

PMID- 9765627
TI  - Dietary intakes of middle-aged European, Maori and Pacific Islands people living
      in New Zealand.
AB  - AIM: To compare dietary intakes of Maori, Pacific Islands and European men and
      women in New Zealand. METHODS: A food frequency questionnaire was used to
      calculate nutrient intakes of 5523 New Zealand workers aged 40 years and over
      (3997 men, 1524 women) from a cross-sectional survey carried out between 1988 to
      1990. RESULTS: Compared with European men and women, Maori women and Pacific
      Islands men and women consumed larger amounts of total energy per day. Age
      adjusted nutrients expressed as percentage contribution to total energy intakes
      showed that Maori and Pacific Islands men and women consumed less carbohydrate,
      fibre and calcium, and more protein, fat, saturated fat and cholesterol than
      European men and women, respectively. These results were consistent with fewer
      servings of cereal and cheese per month, and more servings of red meats, fish and
      eggs in Maori and Pacific Islands participants compared with Europeans, after
      adjusting for age and total energy intakes. Pacific Islands men and women also
      consumed more servings of chicken, fewer cups of milk and fewer servings of fruit
      per month compared to Europeans. Maori men and women consumed more slices of
      bread and fewer servings of vegetables per month compared to European men and
      women. CONCLUSIONS: There were striking differences in dietary habits, food
      selections and cooking practices between European, Maori and Pacific Islands
      participants. Dietary intakes of Maori workers were closer to those of Europeans
      than those of Pacific Islands participants. Ethnic differences were due to larger
      portion sizes and increased frequency of most foods in Maori and Pacific Islands
      participants.

PMID- 9765628
TI  - Are short-stay admissions to an acute general medical unit appropriate?
      Wellington Hospital experience.
AB  - AIM: This audit was performed to ascertain whether the admission of patients to
      the General Medical Unit (Wellington Hospital) for one day or less was
      appropriate. METHODS: Between 1 July 1996 and 30 June 1997, 494 patients were
      admitted to General Medicine for one day or less. The medical records for a
      random sample of 245 patients were reviewed. A modification of the Oxford Bed
      Study Instrument was used to assess the appropriateness of admission. RESULTS:
      Twenty admissions (8.2%) were deemed inappropriate, six patients could have been
      referred to medical outpatients, four were known epileptics who presented
      following a seizure, and none of the others merited admission on severity
      criteria. Ten patients were triaged after 10.00 pm, when discharge becomes more
      difficult. Forty-two patients required an investigation which delayed discharge.
      CONCLUSION: With the present community and investigation facilities available,
      there is no evidence that the majority of 24-hour admissions to acute General
      Medicine are inappropriate.

PMID- 9765629
TI  - The utility of chest radiography in the follow-up of pneumonia.
AB  - AIM: We conducted this study to determine whether chest radiography was
      clinically useful in the follow-up of uncomplicated pneumonia affecting children
      aged between 6 weeks and 15 years. METHOD: We examined the case records of all 78
      paediatric admissions for pneumonia to our hospital over one year. Thirteen
      children were excluded on account of age or other complicating factors. RESULTS:
      Of the 65 study cases, the mean age was 3.5 years (range 0.4-13 years). On
      admission 51 (79%) had cough, 53 (82%) fever, 53 (82%) tachypnoea and 50 (77%)
      had abnormal chest signs. Elevation of C reactive protein was recorded in 43
      (66%) cases and leukocytosis in 42 (65%). All children received initial chest
      radiographs which showed unilobular/lobar changes in 34 (53%), bilobar changes in
      19 (29%) and diffuse abnormalities in 7 (11%). Forty-one patients were followed
      up both clinically and radiologically, usually (31 cases) between four and six
      weeks after discharge. Thirty-seven children had no abnormal symptoms or signs
      and had normal chest radiographs. The remaining four had symptoms and signs,
      their radiographs showed either slight resolution or no change from the admission
      films. CONCLUSION: In cases of uncomplicated pneumonia, follow-up chest
      radiography should be deferred until at least four weeks after discharge and is
      not indicated if symptoms and signs are absent.

PMID- 9765630
TI  - Creating a general practice national minimum data set: present possibility or
      future plan?
AB  - AIM: To assess the feasibility of implementing the recommendations of the New
      Zealand National Minimum Data Set working party in computerised general
      practices. METHOD: Doctors from 12 computerised general practices belonging to
      the Royal New Zealand College of General Practitioners' Dunedin Research Unit
      Computer Network participated in the study (five Dunedin practices, four in rural
      Otago and Southland, and three in Christchurch). A three-month sample of data was
      extracted from practice computers and evaluated for completeness and compliance
      to the national minimum data set structure. Rates of recording practice
      identifier, provider, patient identifiers, sex, ethnicity, government subsidy
      eligibility, consultation identifier and date, prescriptions and Read codes were
      calculated for each practice. RESULTS: Apart from data recorded automatically by
      computers, there was a wide range in the extent of missing data. Of the data
      requiring manual computer entry, patient demography and subsidy eligibility were
      most comprehensively recorded (date of birth 99.9%, sex 99.6%, eligibility to
      subsidies 98.5%). Data with little immediate clinical or management relevance
      were poorly recorded (Read codes 32.4% and ethnicity 5.0%). CONCLUSIONS: It is
      possible to derive a common minimum data set from different computerised general
      practices. However some data elements will be missing unless suitable education
      and support are provided for the doctors and other staff members who record
      patient information.

PMID- 9765631
TI  - Endoscopic band ligation of gastric angiodysplasia.

PMID- 9765632
TI  - How accurate are New Zealand death certificates?

PMID- 9765633
TI  - Monitoring clinical trials.

PMID- 9765634
TI  - Youth suicide rates.

PMID- 9765635
TI  - Dental amalgam.

PMID- 9765636
TI  - Meningococcal disease.

PMID- 9765637
TI  - Smoking kills 31% of Maori.

PMID- 9765638
TI  - Possible idiosyncratic reaction to OC spray.

PMID- 9765639
TI  - Sudden infant death syndrome.

PMID- 9765640
TI  - Burnout in rural general practitioners.

PMID- 9765641
TI  - Licensing of medical practitioners.

PMID- 9765643
TI  - HIV infection in women in New Zealand.

PMID- 9765642
TI  - Licensing of medical practitioners.

PMID- 9765644
TI  - [Contribution of hysteroscopic surgery for the treatment of postmenopausal
      metrorrhagia].
AB  - OBJECTIVES: Determine the effectiveness of hysteroscopic surgery in persistent
      postmenopausal bleeding. PATIENTS AND METHODS: Transcervical resection was
      performed in 176 women between the ages of 46-74 years. A benign cause was noted
      in 135 cases (polyps in 80 and submucous fibroids in 55); 37 patients had no
      significant disease and 4 had endometrial atypical hyperplasia missed in the
      preoperative evaluation. Patients underwent resection of polyp, resection of
      fibroid or endometrial ablation. Major operative complications were rare and
      included 3 perforations and one case of fluid overload. Patients were followed
      for 1-10 years after treatment (mean follow-up 52 months). RESULTS: 167 patients
      completed the study. Clinical manifestations disappeared in 85.2% of the
      patients; 15 patients had hysterectomy after the hysteroscopic procedure and 11
      had repeat transcervical resection. CONCLUSION: Hysteroscopic treatment can be
      effective in carefully selected patients with postmenopausal bleeding or abnormal
      uterine bleeding on hormone replacement therapy. The operative criteria should
      take the causes of bleeding and not just the age of patient into account.

PMID- 9765645
TI  - [Mixed corticomedullary tumor].
AB  - BACKGROUND: Pheochromocytoma and primary hyperaldosteronism rarely occur
      simultaneously. Few cases have been reported in the literature. CASE REPORT: A
      patient explored for hypertension was found to have hypokalemia related to
      primary hyperaldosteronism. Pathology examination of the ablated adrenal showed a
      co-existing pheochromocytoma suspected at history taking although urine
      catecholamines were normal. DISCUSSION: Different pathogenic hypothesis have been
      proposed. Such dual tumors could be a simple coincidence, occur in a particular
      genetic setting, be related to direct contact between cortical and medullary
      tissue leading to reactional cortical hyperplasia, pheochromocytoma produced
      factors stimulating aldosterone synthesis, or factor X, a substance produced by
      cortical adenomas and favoring growth of the pheochromocytoma.

PMID- 9765646
TI  - [Septic shock with coma revealing typhoid fever].
AB  - BACKGROUND: Typhoid fever may be difficult to distinguish from malaria. Septic
      shock, encephalopathy and leukopenia are common features of both diseases. CASE
      REPORT: A 20-year-old South Korean woman was admitted to the intensive care unit
      with coma and shock. Vomiting and abdominal pain were followed by headache,
      prostration, fever and diarrhea. Leukocytopenia, lymphocytopenia,
      thrombocytopenia, rhabdomyolysis and hepatitis were present. Clotting tests were
      normal. The thick peripheral blood film was negative. Salmonella typhi was
      isolated from 6 blood cultures. Treatment associated ceftriaxone 4 g per day for
      5 days, colloid and crystalloid fluids and dopamine. The patient was discharged 2
      weeks later. DISCUSSION: Typhoid fever should be considered as a diagnosis in
      patients with sepsis who come from endemic zones. Abdominal symptoms, prolonged
      fever, coma and delayed headache are particularly contributive signs. Specific
      treatment should be instituted.

PMID- 9765647
TI  - [Vipera ursinii poisoning: 8 cases].

PMID- 9765648
TI  - [Leriche syndrome in a case of atrophic polychondritis].

PMID- 9765650
TI  - [Gossypiboma: an adverse effect or the effect of English language?].

PMID- 9765649
TI  - [Late colonic metastasis of renal cell cancer].

PMID- 9765651
TI  - [Prevention of avoidable iatrogenic effects: the obligation for vigilance].
AB  - PREVALENCE: Latrogenic-related morbidity and mortality rates are difficult to
      determine. Certain estimations in France and other countries have suggested that
      drug-related accidents alone could account for 5 to 10% of all acute
      hospitalizations. This would mean that in France, several thousand deaths are
      caused annuallty by drugs. COST CONSIDERATIONS: Independent of the human aspect,
      health care expenditures related to iatrogenic accidents are substantial. In
      France, the cost would be several ten billion francs. Although the cost/benefit
      ratio remains highly positive, statistically speaking one cannot ignore the high
      cost of severe accidents. THE NOTION OF RISK: There is an urgent need to persuade
      the public opinion that all effective medicines, like all surgical procedures,
      carry a risk. Zero risk does not exist. Patients, and the public in general,
      should come to realize that the objective is to minimize risk inherent in all
      therapies. PREVENTION: It is the duty of the entire health care team to calculate
      the level of acceptable risk and take all the necessary preventive measures. One
      of the objectives of the French National Educational Association for Training in
      Therapeutics (APNET) is to define means of reducing latrogenic effects.

PMID- 9765652
TI  - [Non-ulcerating dyspepsia: role of Helicobacter pylori].

PMID- 9765653
TI  - [Role of diagnostic hysteroscopy in the exploration of postmenopausal
      metrorrhagia].
AB  - DIAGNOSIS: Diagnostic hysteroscopy is an effective method for identifying the
      causes of postmenopausal bleeding. It evaluates the uterine cavity and visualizes
      pathologic conditions such as endometrial polyps, submucous fibroids, and focal
      endometrial abnormalities including adenocarcinoma and its precursors. FURTHER
      INFORMATION: With directed biopsy, diagnostic hysteroscopy also ensures the
      recognition of these lesions.

PMID- 9765654
TI  - [Intracranial hypotension].
AB  - A CLINICAL DIAGNOSIS: Headache which appears in the upright position and subsides
      in the reclining position is suggestive of intracranial hypotension Brain
      magnetic resonance imaging can eliminate an intracranial tumoral process. In most
      cases, contrast images after gadolinium injection show a diffuse hypersignal of
      all the meninges including the falx cerebri and the tentorium cerebelli.
      SPONTANEOUS OR SECONDARY: This clinical presentation is sufficient for diagnosis.
      Occurring after a recent neurosurgical procedure, the intracranial hypotension is
      termed secondary. Inversely, is no known cause can be identified, the condition
      is termed spontaneous. CEREBROSPINAL FLUID: If the clinical manifestations are
      somewhat doubtful, a spinal tap can reveal the very low pressure of the
      cerebrospinal fluid (CSF) although it is advisable to avoid further loss of
      fluid. CSF LEAK: It is generally accepted that intracranial hypotension results
      from leakages of CSF through a breach in the dura mater caused by untreated
      trauma to a particularly fragile area due to a meningocele or an arachnoid cyst
      for example. Occasionally, the CSF leak can be evidenced with isotopic labeling
      used to visualize the breach and guide therapy. TREATMENT: By analogy with the
      spinal tap syndrome, a blood-patch with autologous blood is usually proposed as
      first line medical treatment. Prognosis is generally good.

PMID- 9765655
TI  - [Functional manifestations of osteoarthritis: key points to the clinical efficacy
      of diacerhein].

PMID- 9765656
TI  - [Management of febrile episodes in neutropenic patients].

PMID- 9765657
TI  - [Hirudin for heparin-induced thrombopenia: a new step forward].

PMID- 9765658
TI  - [Once upon a time there was hirudin...].

PMID- 9765659
TI  - [Heparin-induced thrombopenia. Clinical manifestations and physiopathology].
AB  - CLINICAL SIGNS: Heparin-induced thrombocytopenia is a clinically interesting
      model of immunological thrombocytopenia because thrombus formation occurs much
      more frequently than hemorrhage, in some patients, major thrombocytopenia is
      observed with signs of consumption coagulopathy. HIGH INCIDENCE OF THROMBUS
      FORMATION: Venous thrombi predominate with severe consequences such as pulmonary
      emboli or more rarely distal gangrene. Artenal thrombi are less frequent but are
      highly suggestive and often lead to acute ischemia in the lower limbs.
      IMMUNOLOGICAL MECHANISM: Severe forms of heparin-induced thrombocytopenia result
      from an immunological mechanism and are associated with IgG antibody production.
      The Fc fragment of these antibodies activate platelets. Heparin-dependent
      antibodies preferentially recognize antigenic complexes formed by the heparin
      platelet facto 4 association although certain other antigens (IL-8 or NAP-2 are
      also recognized. Thrombus formation results from platelet activation and enhanced
      coagulability which can be favored by antibody binding to endothelial cells and
      synthesis of tissue factor. PRACTICAL ASPECTS: Severe heparin-induced
      thrombocytopenia is particularly frequent in medical and surgical situations
      involving platelet activation and treatments by infractionated heparins. No
      particular phenotype of the IgG Fc receptor has been identified. Likewise no
      specific risk factors have been found. As effective antithrombin therapy is
      required in most cases, Xa inhibitors or thrombin inhibitors are useful.

PMID- 9765660
TI  - [Biological diagnosis and surveillance of heparin-induced thrombopenia].
AB  - THE CHALLENGE: Heparin-induced thrombocytopenia is a diagnostic challenge for the
      clinician. Currently, it is recommended to monitor platelet counts for the first
      3 weeks of heparin therapy. Laboratory counts often may drop off before any
      evidence of a clinical manifestation. LABORATORY TESTS: Confirming the diagnosis
      of heparin-induced thrombocytopenia's often difficult during the acute phase. The
      most widely used tests evidence a platelet activator or proaggregate effect when
      the patient's plasma or serum is exposed to heparin. In France, the platelet
      aggregation test is used almost exclusively although release of labeled serotonin
      is considered to be the reference technique. The antigenic target of antibodies
      produced in heparin-induced thrombocytopenia are identified by their constituent
      platelet factor 4 and heparin sulfate chains. A commercial immunological kit is
      based on this principle. SUBSTITUTION TREATMENT: The laboratory's contribution
      goes beyond positive diagnosis of heparin-induced thrombocytopenia. Indeed,
      disseminated intravascular coagulation must be recognized and a substitution
      treatment proposed together with a measuring the activated partial thromboplastia
      time.

PMID- 9765661
TI  - [Management of a suspicion of heparin-induced thrombopenia].
AB  - A COMPLEX SITUATION: During the acute phase of heparin-induced thrombocytopenia,
      the question must be raised as to whether an antithrombotic therapy is to be
      continued using a compound other than heparin. Later the risk of reintroducing
      heparin again can be discussed. THERAPEUTIC PROPOSITIONS: Excepting vena cava
      interruption, surgical revascularization and thrombolysis, possible therapeutic
      propositions can be divided into two categories; anticoagulants and related
      compounds (hirudin); and oral anticoagulants (anti-vitamin K) and antiplatelet
      agents (aspirin for example). Low molecular-weight heparin cannot be recommended
      in 1998 in patients with heparin-induced thrombocytopenia due to standard
      heparin. IN PRACTICE: Unfractionated heparin or low-molecular weight heparin must
      be stopped immediately. The hematology laboratory should be consulted. It must be
      remembered that prevention, based on a careful assessment of the benefit/risk
      ratio when initiating heparin therapy, is essential.

PMID- 9765662
TI  - [Thrombin and its pharmacologic regulation].
AB  - THROMBUS FORMATION: Thrombin plays a crucial role in thrombus formation. It
      transforms fibrinogen into fibrin and activates platelets. Thrombin has both
      stimulating and inhibiting effects controlling the feedback regulation of
      thrombus formation. Thrombin also stimulates circulating cells other than
      platelets and vascular cells and thus participates in inflammation and wound
      repair accompanying hemostasis and thrombosis. Thrombin's interaction with cells
      is mediated by proteolysis activated receptors (PAR), mainly PAR-1 and probably
      by the recently cloned PAR-3. MECHANISM OF ACTION: Thrombin is an ellipsoid
      shaped serine protease whose active site is located at the bottom of a deep
      groove. One end of the groove bearing the active site carries exosite 1 which
      links with the C-terminal end of hirudine, PAR-1 and PAR-3, fibrinogen and
      fibrin, thrombomoduline and platelet GPIb. Exosite 2 is carried on the top side
      of the molecule opposite the active site. It binds to certain glycoaminoglycanes
      such as heparin. Thrombin's high substrate specificity results from multiple
      interactions which occur between different functional domains and complementary
      domains on the substrate. ACTION OF HEPARIN: The antithrombotic effect of heparin
      results from its catalytic effect on antithrombin III (AT) inhibition of
      thrombin. This effect is however limited because heparin is dependent on the
      concentration of AT and on the of inactivating proteins such as platelet factor
      4. In addition, the inhibitory effect of the AT-heparin complex is limited for
      thrombin bound to the thrombus. Finally, heparin can produce a rare but severe
      complication, heparin-induced thrombocytopenia. Because of these different
      drawbacks, research has been focused on other thrombin inhibitors. DIRECT
      THROMBIN INHIBITORS: The target of these inhibitors is the active site of
      thrombin. Many compounds are under study, including several which can be
      administrated orally. The most advanced clinical trials have been conducted with
      hirudin. Hirudin binds to thrombin at several sites, blocking all the known
      functions of thrombin. The problem of choosing an agent to maintain antithombotic
      therapy in patients with heparin-induced thrombocytopenia remains unresolved.
      Hirudin would be a likely choice as it has no cross reactivity with heparin or
      heparinoids. Promising early results have been reported.

PMID- 9765663
TI  - [Refludan. First line of treatment for type II heparin-induced thrombopenia].
AB  - OBJECTIVES: To assess morbidity and mortality in patients treated with Refludan
      for heparin-induced thrombocytopenia type II in comparison with controls.
      PATIENTS AND METHODS: One hundred thirteen patients with heparin-induced
      thrombocytopenia were treated with Refludan in two studies, HAT1 and HAT2.
      Clinical outcome was assessed in a meta analysis and compared to results in 91
      control patients from a former series. Patients with no associated thrombolytic
      treatment were given an intravenous bolus injection of Refludan (0.4 mg/kg) then
      a continuous infusion of Refuldan (0.15 mg/kg/h). When a thrombolytic treatment
      was associated, patient were given a 0.2 mg/kg) bolus followed by a 0.10 mg/kg/h
      infusion. RESULTS: The rate of thromboembolism complications, amputations and
      death was significantly lower in patients treated with Refludan than in controls.
      There was a clinically acceptable increase in episodes of bleeding with Refludan.
      The benefit/risk ratio was optimum for APTT between 1.5 and 3.

PMID- 9765664
TI  - [Refludan: pharmacologic surveillance study].

PMID- 9765665
TI  - [Effect of prenatal irradiation of rats on morphofunctional state of progeny
      testis].
AB  - It was studied the morphofunctional state of rats testes at the age of 7, 9 and
      19 weeks, which has been developed from embryos gamma-irradiated at dose 1,0 Gy
      during organogenesis (on the 15th day of pregnancy). The analyse of testes
      weight, total content of spermatogenic cells and amount of spermatozoa, RNA and
      DNA content in testicular tissue in prepubertal and pubertal rats irradiated in
      utero at low dose indicates radiation effects in reproductive system, which are
      preserved in postnatal period of animals life for a long time.

PMID- 9765666
TI  - [Proteins induction by cysteamine in Escherichia coli cells].
AB  - It was shown, what in presence of oxygen in broad interval time of treatment in
      E. coli cells was induced line proteins by cysteamine which are proteins SOS-
      repair system and heat--shock system. There are quantitative defined induction
      level RecA, GroEL and DnaK proteins which are members this systems. It was
      allowed to propose what radioprotective action of cysteamine in higher degree is
      defined by its characteristics as induction agent for stress systems of cells.

PMID- 9765667
TI  - [Quantitative analysis of inducible systems of Escherichia coli and Bacillus
      subtilis using radioimmunological methods].
AB  - By RIA dot-blot method two main cell system, system SOS-repair and heat shock
      system, was showed possibility to receive as well qualitative as quantitative
      results influence of different induced agents. Was showed quantitative
      differences in initial levels enzymes of RecA and CroEL in different strains of
      E. coli, as well of principle possibility to using received antibody, which has
      high specific to this enzymes, for investigation reactions this systems in the
      other bacterial species, such as Bac. subtilis.

PMID- 9765668
TI  - [Aorta dilatation after prolonged gamma-irradiation].
AB  - It is shown on isolated aorta preparations that prolonged gamma-irradiation of
      rats results in depression of endothelium-dependent and endothelium-independent
      vasodilatation responses to beta-adrenoceptors stimulation by isoprenaline and M
      cholinoceptors by carbachol.

PMID- 9765669
TI  - [Analysis of temperature and radiation-induced effects in model and natural
      biomembranes using UV-spectroscopy method].
AB  - Effects of low-dose gamma-irradiation (up to 1 R) upon UV absorption spectra of
      water dispersions of egg yolk lecithin (1:1) and samples of rat liver homogenate
      were studied. Clearly detectable changes could be observed in the 200-220 nm
      range already under dose loads of several mGy. Radiation sensitivity was shown to
      be essentially temperature dependent, being the highest at physiological
      temperatures.

PMID- 9765670
TI  - [Quantitative characteristics of radiation sickness clinical manifestations in
      large-sized laboratory animals exposed to extra-lethal radiation doses. The
      endocrine system reactions in dogs and monkeys].
AB  - The dynamics of cortisol, insulin and triiodothyronine content of the blood has
      been studied in dogs and two monkey species exposed to electron and gamma-neutron
      radiations in a wide supralethal--dose range. A calculated value--index of the
      endocrine status--has been used for integral estimation the function of the
      endocrine system. A considerable disintegration of the functions of separate
      endocrine glands has been observed, which correlates with degree of clinical
      manifestations in animals and radiation dose.

PMID- 9765671
TI  - [Comparative characteristics of lipids, lipoproteins and free radical processes
      in blood of rabbits after ionizing irradiation and dietary cholesterol
      administration].
AB  - Comparative study of spectrum of lypoids and lipoproteins has been conducted and
      also of parameters of free radical processes in blood after exposure of organisms
      of experimental animals to ionizing irradiation in dose of 5 Gy and inclusion of
      cholesterol into diet. Intake of cholesterol to experimental animals irradiated
      caused specific impact on indices studied testifying about deep changes in
      metabolism. It is important during analysis of complex set of postradiation
      metabolic symptoms observed in clinics.

PMID- 9765672
TI  - [Fatty acids metabolism of rat liver after extra-lethal gamma-irradiation].
AB  - The effect of acute gamma-irradiation of rats at super lethal doses from 25 to
      270 Gy on the synthesis and amount of fatty acids, neutral lipids and
      phospholipids of liver was studied 48 h after gamma-irradiation. It was shown,
      that the synthesis of fatty acids, cholesterol, cholesterol ethers and
      phospholipids was activated 48 h after irradiation at 25-100 Gy, but the
      irradiation in the doses above 100 Gy inhibited the activation of lipid
      synthesis. The amount of fatty acids and neutral lipids of the rat liver
      decreased at 15-100 Gy. After irradiation at 200, 270 Gy the fatty acid content
      increased significantly, while the decrease of concentration of cholesterol
      ethers remained under the control level. This is assumed to be a result of the
      radioresistance to a some degree in the system of fatty acid synthesis of the rat
      liver to the gamma-irradiation in the super lethal doses.

PMID- 9765673
TI  - [Elevation of serum glucose concentration after administration of 5'-AMP to rats
      and modulation of this process dynamics following single gamma-irradiation at 1
      Gy dose].
AB  - Injection of exogenic 5'-AMP to rats was accompanied by pronounced and transient
      adenosinemediated elevation of serum glucose concentration. Both efficiency and
      duration of the observed hyperglycemic effect were increased within the first
      week after single whole-body gamma-irradiation (137Cs) of the animals at 1 Gy
      dose. These data suggest modification of purinergic regulation of some processes
      of carbohydrate metabolism and disturbance of the organism tolerance towards the
      glucose following 1 Gy gamma-irradiation.

PMID- 9765674
TI  - [Fluorescent spectral study of synthetic activity of animal blood lymphocytes
      under continuous gamma-irradiation].
AB  - The effect of continuous gamma-irradiation with dose rate 14.4 cGy/day on the
      synthetic activity of rat and rabbit blood lymphocytes stained with acridine
      orange was studied by fluorescent microspectrometry. The changes of the synthetic
      activity of blood lymphocytes, described by the parameter alpha, occurred in four
      main stages. The essential differences in changes of synthetic activity between
      rat and rabbit were observed at the first stage. In the rats, parameter alpha
      sharply increased, as a result of the stimulatory effect of low dose irradiation.
      In the rabbits, being more radiosensitive, at the first stage, parameter alpha
      was about control values, as a result of two opposite directed processes,
      stimulatory and damaging. At the fourth stage, decrease of the synthetic activity
      was both in the rats and in the rabbits owing to damaging effect of continuous
      gamma-irradiation during long time.

PMID- 9765675
TI  - [Natural antihistone antibodies: their possible role in genesis of radiation
      injuries].
AB  - The substantial decrease of free natural antibodies reacting with histones under
      effect of 4 Gy total dose radiation in sera of healthy animals was established.
      It is supposed that the binding of natural antihistone antibodies with histones
      reduces the cytotoxic reactivity of histones released from cells under effect of
      ionizing radiation. It was determined that complexes of antihistone antibodies
      and histones get the ability to react with DNA. The possible biological role of
      these complexes is discussed.

PMID- 9765676
TI  - [The study of influence of acoustic oscillations on the immunogenesis].
AB  - It was found out, that immunomodulative action of low frequency acoustic
      oscillations (LFAO) is mediated in mice by enhancement or decreasing of distinct
      stages of immunogenesis. Exposure to this factor at intensity of 80 dB varied
      number of cells in lymphoid organs, enhanced cell proliferation, improved
      cooperative interaction of thymocytes and bone marrow cells in immune response,
      caused increase of allogenic stem cells inactivation. On the contrary, exposure
      to LFAO at the acoustic pressure of 130 dB caused alternative effects, as
      inhibition of immunocompetent cells in interaction.

PMID- 9765677
TI  - [Long-term effects of chronic radiation exposure on the level of somatic
      mutations in peripheral blood cells].
AB  - The level of comatic mutations was studied at GPA locus and in the TCR system at
      late times since the onset of radiation exposure in persons exposed to chronic
      radiation accidents at the Mayak Production Association in the period 1949-1952.
      Individuals with predominantly external gamma-exposure and those with
      predominantly internal (mainly due to 90Sr) exposures have been identified among
      the exposed population. The average dose to red bone marrow made up 121.5 cSv
      with individual values ranging from 11.0 to 462.7 cSv. An increased frequency of
      TCR-mutant lymphocytes was noted for exposed subjects. The level of GPA-variant
      erythrocytes of different types in the study group did not differ from the
      respective value registered in control. The analysis of TCR status showed no
      dependence of mutant cell frequency on exposure dose. The assumption is made that
      the rate of exposure dose and the nature of its formation (chronic exposure)
      exert a decisive influence on the level of somatic mutations in peripheral blood
      cells in humans.

PMID- 9765678
TI  - [Delayed cytogenetics effects of chronic irradiation of South Ural population].
AB  - The evaluation of remote cytogenetic consequences was studied in population,
      irradiated at low level during 40 years and more preferentially internally. Mean
      level of exposure was in 1950 year at maximum--0.2 Sv/year. In 1993 year it was
      equal 1.95 mSv/year. It was revealed statistically significant increasing of
      chromosome type of aberrations in lymphocytes of irradiated people in comparison
      with control ones. The incidence of chromosome type exchanges in irradiated
      individuals comprised 0.43 per 100 cells, and 0.17 per 100 cells in the control.

PMID- 9765679
TI  - [Antitoxic features of magnesium oxide under combined radiation and thermal
      injury].
AB  - Male Wistar rats were exposed to 7.5 Gy total body gamma radiation followed to
      the additional full-thickness thermal bum. It was shown, that single
      administration of magnesium oxide in 1 hour after combined injury significantly
      corrected the early signs of endogenous intoxication. The level of bacterial
      endotoxemia decreased as well as serum concentration of toxic oligopeptides;
      general blood serum toxicity has been reduced too. Four-fold magnesium oxide's
      using as an enterosorbent in combination with antibiotics (doxycyclini,
      gentamicini or ciprofloxacin) has ensured 73-100% rats survival. All untreated
      animals dead within 30 days after combined injury.

PMID- 9765680
TI  - [Effect of substances, absorbing ultraviolet irradiation on Bacillus subtilis
      resistance to inactivation and mutagenic action of natural sunlight].
AB  - Substances, absorbing UV-irradiation from sunlight (triptophan, cistein,
      catalase) decrease Bacillus subtilis resistance to sunlight-induced lethal and
      mutagenic damages. Possible, they act as exogenous photosensitizers. Tryptophan
      was found to be the most active photosensitizer. Cistein and catalase are not so
      active. Casaminoacids being present in the bacterial suspensions during
      illumination protect bacteria from mutagenic action sunlight. In this studies we
      can demonstrate, that sunlight damage B. subtilis membranes and allows substances
      to penetration into cells. Following, that polishing of the environmental by
      chemical agents can strength genetic risk for organisms permanently exposure to
      sunlight.

PMID- 9765681
TI  - [The effect of ionizing radiation and radiosensitizing agent AK-2123 on luminol
      dependent chemiluminescence of human neutrophils].
AB  - The method of luminol-dependent chemiluminescence (CL) was used to study the
      influence of gamma- and fast electrons-irradiation on secretion of reactive
      oxygen species of neutrophils in enrich suspension and in presence of all blood
      components. In vitro gamma-irradiation (from 5 to 25 Gy) of the neutrophil
      suspension inhibited spontaneous CL and activated stimulated by phorbol-12
      myristate-13-acetate (PMA) (100 nM) in the period 30-60 min after radiation. The
      time of maximum PMA-stimulated CL amplitude was decreased with the dose range
      from 2(5) to 25(30) Gy for gamma- and fast electrons-irradiation. The addition of
      radiosensitizer AK-2123 (0.05% or 2.2 mM) depressed the early PMA-stimulated CL
      response on gamma- and fast electrons-irradiation. The obtained results suggest
      that this effect is connected with influence of AK-2123 on ion canals of
      neutrophils.

PMID- 9765682
TI  - [The state of one of the erythropoiesis regulatory mechanisms after ionizing
      radiation exposure].
AB  - New quantitative criteria of erythrocytes functional state, based on automated
      registration of acid erythrogramme parameters, have been proposed. Enwidened
      analysis of adaptive processes in rats erythropoietic system after ionizing
      radiation exposure (gamma-rays, 60Co, in doses 0.5; 1.0 and 6.0 Gy) has shown,
      that existing in norm mechanism of stimulating effects of dieresis products on
      genesis of young red cell forms has been maintained only at exposure 0.5 Gy and
      stops to function at higher gamma-ray irradiation doses.

PMID- 9765683
TI  - [Study of 137Cs transfer across the placenta to the rat fetuses and effect of
      ferrocin on these processes].
AB  - The 137Cs placental transfer to the fetuses was studied using a daily oral 137Cs
      administration to pregnant rats. At day 19 of gestation, the fetuses receive 0.8%
      of the amount administered to the female. A daily application of ferrocinum
      reduces the 137Cs content of the female body by 82-84% and decreases the fetal
      accumulation down to 0.14%.

PMID- 9765684
TI  - Historical overview of the project "Sunshine" in Belgium.
AB  - The project "Sunshine" was originally focused on the study of strontium 90 from
      the world-wide radioactive fallout and its effects on man. It was one of the most
      important projects the USAEC had ever had. It was being conducted as a scientific
      study, the primary purpose of which was to discuss the scientific truth and
      present the facts publicly. The implementation of the Project in Belgium started
      in 1958 and developed into two main directions: a) Environmental survey and b)
      Experimental research in both natural and controlled conditions. The paper
      described the characteristics of the seven stations "Sunshine" distributed in the
      typical agricultural regions of the country, their sampling, the analytical
      procedures used and the results obtained (relationship rain/grass; milk/grass;
      the observed ratio etc.). Experimental researches performed in natural conditions
      aimed to investigate the influence of the yield of the grass/crops on the direct
      retention of the deposited fission products; other experiments watched the
      transfer of radiostrontium and radiocesium from soils to plants; several
      experiments on artificially contaminated pastures grazed by cows allowed to
      clarify the importance of such factors as the methods of feeding and types of
      pastures for the transfer of major radionuclides to milk. Experimental researches
      conducted in controlled conditions dealt with such topics as study on the
      retention of strontium 90 in soil, studies on foliar contamination by
      radiostrontium and radiocesium, absorption and distribution in plants of Sr and
      Ca, discrimination between Sr and Ca during the transfer from feed to cow milk,
      study on the contamination by the major fission products of the milk products.
      Finally tentative countermeasures were tested: application of significant amounts
      of stable strontium in contaminated soils and influence of alginate on
      radiostrontium absorption from contaminated milk to piglets.

PMID- 9765686
TI  - Induction chemotherapy followed by simultaneous hyperfractionated
      radiochemotherapy in advanced head and neck cancer. A pilot study.
AB  - PURPOSE: To evaluate the feasibility of induction chemotherapy followed by
      concomitant chemotherapy and hyperfractionated irradiation in locally advanced,
      inoperable head and neck cancer. METHODS: A pilot study was undertaken comprising
      3 cycles of cisplatinum (100 mg/m2, day 1) and 5-fluorouracil (1000 mg/m2 in
      continuous intravenous infusion over the first 120 h) followed by bifractionated
      radiotherapy applied to tumor/involved lymph nodes up to the dose of 74.4 Gy
      given in 2 fractions of 1.2 Gy daily for 5 days a week combined with concomitant
      weekly cisplatinum infusion (50 mg/m2). RESULTS: Six patients were enrolled in
      the study. All of them completed the protocol therapy. Severe mucositis and
      myelotoxicity were the most common acute side effects observed in all and in 5 of
      the patients, respectively. Acute toxicity required interruption of concomitant
      chemotherapy in 5 cases and in 2 interruption of radiotherapy was necessary.
      Opioid analgesic parenteral therapy was administered in 4 patients. Three of them
      had to be hospitalized. One patient experienced cerebral stroke 1 day after the
      completion of therapy and died 7 days later. Due to high acute toxicity, patient
      accrual was terminated after 6 patients. At the mean follow-up of 17 months, 4
      patients are alive, 3 of them are free of disease and in 1 local progression has
      been diagnosed. CONCLUSIONS: High acute toxicity of induction cisplatinum and 5
      fluorouracil followed by concomitant cisplatinum and hyperfractionated
      irradiation calls for less toxic treatment schedules in locally advanced
      inoperable head and neck cancer.

PMID- 9765685
TI  - [Endocrine orbitopathy: comparison of the long-term result and classification
      after radiotherapy].
AB  - BACKGROUND: This study compares 4 classifications in patients with progressive
      refractory Graves orbitopathy (GO) and examines their prognostic value in long
      term follow-up. PATIENTS AND METHODS: From 1984 to 1994, 60 consecutive patients
      (49 female, 11 male) received 20 Gy (10 x 2 Gy) radiotherapy with 6 MV Linac
      photons. Ocular symptoms and functional impairment was evaluated according to 4
      GO-classification systems: Werner-, modified ATA- and Stanford-Score and
      Ophthalmopathy-Index (OI) according to Grussendorf. In addition, all patients
      noted their subjective response on a linear scale (0 to 100%). RESULTS:
      Improvement was achieved within 1 year after radiotherapy according to the Werner
      Score in 28 (47%) patients in > or = 1 symptom category, according to the
      modified ATA-score in 48 (80%), the Stanford-score in 47 (78%) and the OI-Score
      in 55 (92%) patients (reduction of > 2 points). The Werner-Score correlated less
      to the other scores (coefficient r < 0.5) than the other scores among themselves
      (r approximately 0.9). The ATA-Score improved in the different symptom categories
      between 47% (stage VI) and 87% (stage V). The OI-Score was reduced by a mean of 6
      points. The patients reached a mean subjective improvement of +70 +/- 25%. Acute
      or chronic side effects were not observed. In multivariate analysis the "male
      gender" (p = 0.08), a "symptom duration prior to radiotherapy > 1 year" (p =
      0.14) and a "high symptom category" (p = 0.11) indicated a negative prognostic
      trend. CONCLUSIONS: External radiotherapy is effective for severe, progressive GO
      after pretreatment. A minimum follow-up of at least 12 months and standardized
      classification and success criteria are required.

PMID- 9765688
TI  - [Remarks on the dosage problem in HDR brachytherapy].
AB  - BACKGROUND: In HDR brachytherapy activity distributions can be achieved which
      were unknown in LDR brachytherapy. For this reason the classical dosage systems
      can only be used with caution in HDR brachytherapy. METHODS: Different simple
      applications are used to investigate the effect of various activity distributions
      on dose and integrated reference air kerma. RESULTS: Within the classical LDR
      dosage systems dose and integrated reference air kerma were equivalent. Due to
      the possibility to "optimize" the activity distribution in HDR brachytherapy this
      is not longer the case. Different optimization algorithms and different
      optimization goals may lead to quite different activity distributions and
      different integrated reference air kerma values even if the source positions are
      the same. For target volume oriented optimization schemes a dosage system is
      described which is based on dose-volume-histograms. CONCLUSIONS: A widely
      accepted dosage system in HDR brachytherapy is missing. The dosage system
      described in this paper may be useful in solving this problem.

PMID- 9765687
TI  - [D-xylose test of resorption as a method to determine radiation side effects in
      the small intestine].
AB  - BACKGROUND: The D-xylose test is the most important method to determine a
      disorder of carbohydrates resorption in proximal small intestine. The application
      is based on an impaired resorption due to pathological change of small intestine
      surface, leading to a decreased blood level or decreased excretion in urine.
      PATIENTS AND METHOD: D-xylose test was applied in 91 patients before, shortly
      after, 1/2 and 1 year after radiotherapy. All patients received an abdominal
      radiotherapy. We determined the blood level of D-xylose by a capillary blood
      sample 1 hour after oral D-xylose administration. RESULTS: A significant decrease
      of the mean blood level of D-xylose to 1.88 mmol/l was determined after
      radiotherapy in comparison with 2.17 mmol/l before radiotherapy. Half a year
      after radiotherapy the mean blood level of D-xylose returned to normal. Regarding
      a threshold value of D-xylose blood level of 1.70 mmol/l 29 patients (32%) showed
      a pathologically decreased D-xylose resorption after radiotherapy. Twenty out of
      the 29 patients already showed a normal resorption half a year after the
      determination of the resorption disorder, 5 patients after 1 year and 4 patients
      after 1 1/2 years. There was no correlation between the detection of a disorder
      of D-xylose resorption and of a loss of body weight. The acute clinical side
      effects seemed to be more marked in connection with a disorder of D-xylose
      resorption, but this correlation is not significant. Eleven or 14 of the 29
      patients, respectively, with pathologically decreased D-xylose resorption only
      had complaints of lower or upper gastrointestinal tract, respectively, and 10
      patients did not have abdominal complaints at all. CONCLUSIONS: The D-xylose test
      is an important and simple method for determination of radiogen induced
      carbohydrate malabsorption in proximal small intestine. By means of it radiation
      side effects on small intestine can also be determined in patients who are
      otherwise free of complaints.

PMID- 9765689
TI  - [First experiences with computer-assisted frameless stereotactic interstitial
      brachytherapy (CASIB)].
AB  - PURPOSE: To reach an optimal treatment result and to avoid damage to critical
      structures a homogeneous dose distribution in the tumor volume with a rapid
      decreasing dose to the surrounding structures is necessary. Fractionated
      interstitial brachytherapy of tumors in the ENT region employing needles depends
      on exact localization of the target volume during all fractions. Therefore
      reproducibility of positioning of the needle(s) plays an important role. MATERIAL
      AND METHODS: We used the ISG Viewing Wand system in combination with the Vogele
      Bale-Hohner (VBH) head holder and a new targeting device. Point of entrance,
      pathway, and target point of the needle were planned and insertion of the needle
      simulated in advance. To date we have treated 7 patients with inoperable tumors
      in the ENT region. The actual position of the needle in the control CT was
      compared to the planned position. RESULTS: The accuracy of positioning of the
      needle depended on the location of the tumor. In a patient with a recurrent
      retroorbital adenocarcinoma the mean accuracy was 1 mm. Due to soft tissue
      displacement in the neck region and the resulting necessity to readjust the
      targeting device the needle was placed with a mean deviation of 15 mm between the
      planned and the actual position. CONCLUSIONS: Computer-assisted frameless
      stereotactic interstitial brachytherapy allows for precise, reproducible and
      preplanned insertion of hollow needles into target structures closely adherent to
      the surrounding tissue, thus avoiding damage of neighbouring structures. This
      technique is of great advantage in treating deeply seated tumors which are fixed
      to bony structures, especially at the skull base. Inaccuracy in the neck region
      caused by soft tissue shift requires improvement of the immobilization in this
      region.

PMID- 9765690
TI  - [Spinal metastases of malignant gliomas].
AB  - PURPOSE: Extracranial metastases of malignant gliomas are rare. We report 2 cases
      with spinal metastases in patients suffering from glioma. PATIENTS AND METHOD:
      Two patients (33 and 57 years old) developed spinal canal metastases of a
      glioblastoma multiforme and anaplastic astrocytoma Grade III respectively 25 and
      9 months after surgical resection and radiotherapy. Both metastases were
      confirmed pathohistologically. RESULTS: Intraspinal metastases were irradiated
      with a total dose of 12.6 Gy and 50 Gy. Treatment withdrawal was necessary in one
      patient due to reduced clinical condition. Regression of neurological symptoms
      was observed in the second patient. CONCLUSIONS: Spinal spread of malignant
      glioma should be considered during care and follow-up in glioma patients with
      spinal symptoms.

PMID- 9765691
TI  - Treatment of radiation proctitis with hyperbaric oxygen: what is the optimal
      number of HBO treatments?
AB  - AIM: Our objective was to investigate the effectiveness of hyperbaric oxygenation
      (HBO) in the treatment of radiation proctitis. The current literature was
      reviewed with regard to the necessary number of HBO treatments. PATIENTS AND
      METHODS: Two patients with proctitis after pelvic irradiation were treated with
      40 and 38 HBO treatments, respectively. Hyperbaric oxygenation was delivered at
      240 kPa over 90 min. RESULTS: In one patient, proctosigmoidoscopy showed a
      significant improvement after 40 HBO sessions. The other patient interrupted
      therapy after 38 HBO treatments without subjective change. The reported number of
      HBO sessions for a successful treatment of radiation proctitis ranges from 12 to
      90. CONCLUSION: HBO should be considered before more invasive treatment
      modalities are performed for radiation proctitis.

PMID- 9765692
TI  - [Oxygenation status of squamous cell carcinoma of the head and neck: comparison
      of primary tumors, their neck node metastases and normal tissue].
AB  - AIM: Investigation of the relationship between the pO2-status of primary tumors,
      their cervical neck node metastases and normal tissues in squamous cell
      carcinomas of the head and neck. PATIENTS AND METHODS: Pretreatment oxygenation
      of primary tumors, their neck node metastases and of the contralateral
      sternocleidomastoid muscle was assessed in 16 patients with histologically proven
      advanced squamous cell carcinomas of head and neck. Oxygenation was measured with
      a polarographic microelectrode system (Eppendorf-pO-Histograph). Using CT/MRT
      additionally the volume of the tumors was estimated. RESULTS: A highly
      significant correlation existed between the median pO2 of primary tumors and
      their neck node metastases and between the relative proportion of hypoxic values
      (< 5 mm Hg) of both anatomic sites (both p = 0.0001) (Figure 1). Primary tumors
      were not different from their neck node metastases, neither regarding the pO2
      median values nor in view of the relative frequency of hypoxic values (Table 1).
      No correlation was found between the volume of primary tumors and the one of
      their neck node metastases. For volume of tumors and the oxygenation status no
      relationship was found as well. Significantly different was the median pO2 in the
      muscles from the one of the malignant tissues (p = 0.0004). CONCLUSION: The
      results suggest that for to estimate the oxygenation status of squanious cell
      carcinomas of the head and neck pO2 measurements of primary tumors and neck node
      metastases are equally sufficient.

PMID- 9765693
TI  - [A randomized trial of concurrent chemoradiotherapy versus radiotherapy in
      advanced carcinoma of the uterine cervix].

PMID- 9765694
TI  - [Isolated vaginal recurrences in endometrial carcinoma: treatment results using
      high-dose-rate intracavitary brachytherapy and external beam radiotherapy].

PMID- 9765695
TI  - [Continuous intravenous infusional 5-FU compared with bolus administration in
      metastatic colorectal carcinoma].

PMID- 9765696
TI  - [Adjuvant radio-chemotherapy is effective in the treatment of Dukes B and C
      rectal cancer: results of a randomized controlled Norwegian trial].

PMID- 9765697
TI  - [Management of the unscheduled interruption or prolongation of a radical course
      of radiotherapy].

PMID- 9765698
TI  - [Endonasal sequelae after hypophysectomy].
AB  - Each year, 15 transvestibular transseptal transsphenoidal hypophysectomies are
      performed in Lausanne. The aim of the study was to determine the complications
      rate of our procedure and their influence on the life quality of patients.
      Questionnaires were sent to 178 patients, operated between 1984 and 1995. 125
      questionnaires were returned. Out of those, 73 patients accepted to undergo a
      control rhinoscopy. The most frequent complains were nasal obstruction and
      crusting (38% each), whistling while breathing through the nose (12%), and
      stuffiness of the upper lip or teeth (7%). Endoscopically, we detected an
      anterior septal perforation in 10 cases (13.7%), 8 (80%) of which were
      symptomatic and a posterior septal perforation in 6 cases, all of them being
      asymptomatic. Finally, 36% of the patients had no complains and 19% of them had
      an improvement of respiration after the operation. Of the whole series of 178
      patients, only 5% had complications requiring an ENT follow-up for longer than 6
      months after having been operated.

PMID- 9765699
TI  - [KTP laser in the upper airways in children: preliminary study on 27 lesions].
AB  - The KTP Laser was recently introduced in otolaryngology, and is increasingly
      used. This report describes treatment of 27 upper airway lesions in 24 children
      using KTP Laser over a two year and half period at the Children's Hospital of La
      Timone in Marseille. Comparison of results with CO2 Laser were made for the three
      most frequent pathologies of the series which were choanal atresia (n = 14),
      laryngotracheal stenosis (n = 6) and laryngeal paralysis (n = 3). The convenience
      of fiber delivery, concomitant telescopic control and low grade oedematous
      reaction are the main advantages over the CO2 Laser. As reported in the
      literature, we observed that healing was longer for KTP Laser than for CO2 Laser.
      Delay to healing may be an advantage in the management of choanal atresias and
      laryngeal stenosis.

PMID- 9765700
TI  - [Gadolinium and contrast medium MRI of the acoustic nerve in patients with
      meningeal neuritis and acoustico-facial syndrome].
AB  - Twelve cases of vestibular neuritis were investigated in gradient echo MRI with
      gadolinium. Only 3 severe cases associated with an acoustico facial syndrome (2
      cases of herpes zoster oticus and one case after influenzae) demonstrated focal
      enhancement within the internal auditory canal on post contrast T1 weighted
      images. This enhancement involved at least 2 differents nerves. These 3 severe
      cases associating sensory neural hearing loss and facial palsy revealed a
      meningeal reaction after cerebrospinal fluid examination. The enhancement lasted
      a long time (up to 10 months) in one case of RAMSAY HUNT syndrome associated with
      a chronic lymphocytic leukemia. The MRI was able to confirm the anatomical
      reality of the vestibular neuritis and more precisely of the meningoneuritis and
      gave arguments for the theory of the polyneuropathy of Adour. Enhancement at MRI
      seems correlated with the severity of the affection (permanent vestibular
      areflexia in 3 cases and permanent hearing loss in 1 case).

PMID- 9765701
TI  - [Dilator muscles of the pharynx and their implication in the sleep apnea syndrome
      of obstructive type. Review of the literature].
AB  - Pathophysiology of the obstructive sleep apnea syndrome shows three components:
      intra and peripharyngeal obstacles, excessive pharyngeal wall compliance and
      upper airway dilator muscle dysfunction. The intent of this paper is to provide
      an overview of the anatomy, histology, physiology and pathophysiology of the
      upper airway dilator muscles based on previously published articles. The upper
      airway dilator muscles can be separated in three different systems, main and
      accessory dilators, local and regional. They act in synergy. Their contraction
      occurs at the beginning of inspiration, thus maintaining opened the pharyngeal
      lumen through inspiration. Their action is modulated by several chemo or physical
      stimuli. In some apneic patients, these muscles demonstrate a dysfunction:
      hyperactivity during wakefulness, electromyogram wave amplitude reduced, delayed
      contraction during sleep and abnormal response to stimuli. This dysfunction might
      be due to neuromuscular histological abnormalities, a "fatigue" phenomenon or a
      central nervous command abnormality. Current explorations underlining an upper
      airway dilator muscle dysfunction will enable practitioners to decide which
      treatment is best and understand therapeutical failures; it will also help
      develop new therapeutical techniques such as functional electrical stimulation of
      the hypoglossal nerve/upper airway dilator muscles.

PMID- 9765702
TI  - [Spheno-ethmoidal rhinoscleroma. Report of a case and review of the literature].
AB  - We report an unusual case of spheno-ethmoidal rhinoscleroma. This chronic
      granulomatous disease occurs sporadically in Western Europe. Culture is necessary
      for diagnosis showing the causative organism of rhinoscleroma, Klebsiella
      rhinoscleromatis. Immunocytochemistry is used in any suspicious case with a
      negative culture. Antibiotics are the mainstay of therapy for several weeks,
      using ciprofloxacine or rifampicin, until the nasal biopsies demonstrated no
      Klebsiella organism.

PMID- 9765703
TI  - [Etiological diagnosis of sensorineural deafness in children: a year-long review
      of genetic counseling for deaf people].
AB  - From February 1996 to January 1997, 74 patients from 53 sibships underwent
      genetic counselling for sensorineural deafness at the Pasteur Hospital, Paris,
      France. Genetic counselling was based on the etiological diagnosis of the hearing
      impairment, by an audiological and non-audiological examination program. At the
      first examination, 31 families presented with a familial deafness and 22 families
      with apparently one affected individual. However, familial audiological
      examinations revealed familial deafness in 5 of these 22 families. Consequently,
      a total of 36 families had hereditary hearing impairment and the etiological
      groups showed the following distribution: non-syndromic deafness (14 families),
      syndromic deafness (12 families), probable syndromic deafness (5 families), and
      incomplete assessment (5 families). Out of the remaining 17 families in which
      affected individuals were sporadic cases, the etiological groups were as follows:
      acquired deafness (2 families), probable syndromic deafness (5 families), unknown
      cause (5 families), and incomplete assessment (5 families). Etiological
      assessment is discussed, with reference to the cost-effectiveness of this
      examination program. In light of this preliminary report, we present a model of
      assessment for the etiological diagnosis of sensorineural deafness in children
      and young adults.

PMID- 9765705
TI  - [Microcystic sclerosing adnexal carcinoma: 2 case reports. Diagnostic and
      therapeutic difficulties].
AB  - Microcystic adnexal carcinoma is a recently described malignant neoplasm of
      adnexal structure. It remains frequently misdiagnosed. These tumors are
      characterized by their slow progression and by local aggressivity with local
      recurrences. The best treatment appears to be surgical excision with
      microscopically controlled margin. We report two cases of microcystic adnexal
      carcinoma recently observed at Institute Gustave Roussy.

PMID- 9765704
TI  - [Cochleovestibular disorders associated with hemifacial spasm: an outcome after
      microvascular decompression of the facial nerve].
AB  - Twelve patients underwent microvascular decompression by retrosigmoid approach to
      relieve severe hemifacial spasm. The surgery was done under intraoperative
      monitoring of the auditory function. Assessment at Day 2, Day 10, 2 months and 6
      months after the operation found that the surgery had resulted in 9 recoveries, 3
      improvements and 1 failure. Brain stem auditory evoked potentials monitoring
      showed that the interposition of Teflon between the vascular loop and the facial
      nerve is a critical stage for the auditory function. Six of the twelve patients
      were also complaining of cochleo-vestibular disorders: vertigo and tinnitus, or
      hearing loss and tinnitus, or vertigo alone. The surgery improved at least one of
      these cochleo-vestibular symptoms in each one of the patients. There was one
      hearing improvement, vertigo disappeared in three cases out of four, and tinnitus
      disappeared in four cases out of five. The possibility of a concomitant
      compression of cochleo-vestibular and facial nerve was investigated using
      cochleovestibular tests, radiological data and intra-operative findings.

PMID- 9765706
TI  - [Amelanotic melanoma of the frontal sinus: a case report].
AB  - We report a case of frontal sinus amelanotic melanoma in a 76-year-old man. The
      diagnosis was based mainly on immunohistochemical studies. Despite an aggressive
      therapeutic regimen associating surgery and radiotherapy, outcome was fatal 8
      months after onset of symptoms.

PMID- 9765707
TI  - [Nasopharyngeal perforation: an exceptional accident during digestive endoscopy].
AB  - A case of an endoscopic nasopharynx perforation is reported. As we known, this
      accident has never been described. During introduction of a duodenal tube
      appeared a subcutaneous neck emphysema. Radios revealed pneumomediastinum,
      pneumoperitonitis and retropneumoperitonitis. Nasofibroscopy affirmed the
      diagnosis. The too fast death of this 92 years old patient didn't allow an
      adapted therapeutic.

PMID- 9765708
TI  - [A report of two familial cases of Michel syndrome (bilateral agenesis of the
      inner ear)].
AB  - In two siblings, wearing conventional hearing aid, presenting profound but not
      total congenital deafness, with no particular antecedents, the imaging destined
      to confirm the indication of a cochlear implant revealed a total bilateral
      agenesis of the inner ear. In one of the children, this imaging was confirmed by
      an exploration of the middle ear performed during a tonsillectomy that was
      otherwise necessary. We will summarize the literature concerning Michel's
      Disease, exceptional in its princeps form, and we will discuss the manner of
      action of conventional devices in these cases which are a priori without any
      sensorial element.

PMID- 9765709
TI  - [Intra-labyrinthine schwannomas: a report of two cases].
AB  - Intralabyrinthine schwannomas are rare tumors of vestibule, cochlea, semicircular
      canals, or some combination of these three. In the past, they have been found at
      autopsy or as incidental finding at surgery. Since the advent of magnetic
      resonance imaging (MRI) with intravenous gadolinium contrast, the preoperative
      diagnosis is possible. We report two cases of intralabyrinthine schwannoma: one
      case of intralabyrinthine schwannoma extended into the internal auditory canal
      (IAC), a second case of tumor restricted to the vestibule. No characteristic
      clinical presentation of this tumor is reported in the literature. In patients
      with vestibular weakness (vertigo and no response of caloric testing), MRI with
      gadolinium contrast can make the diagnosis of intravestibular tumor. In patients
      with the more common IAC acoustic neuromas, MRI can demonstrate extension of
      tumor into the labyrinth; diagnosing this extension preoperatively is important
      to plan surgical treatment.

PMID- 9765710
TI  - ["Aquatic" dissection of the facial nerve for the surgery of acoustic neurinoma].
AB  - We describe a procedure facilitating dissection of the facial nerve from acoustic
      neuromas, consisting of a pulsed irrigation of serum. This seems to minimize
      nerve manipulation and thus surgical trauma.

PMID- 9765711
TI  - [A sinus neglected for so long...].

PMID- 9765712
TI  - [Acute and chronic sphenoid sinusitis. Review of the literature].
AB  - Isolated involvement of the sphenoid sinus is a relatively uncommon entity. We
      present a review of the most important series. Acute and chronic diseases are
      separated. Acute sphenoid sinusitis is a potentially catastrophic infectious
      disease. It is frequently initially misdiagnosed, and, due to the severe
      intracranial complications, a genuine medical and surgical treatment is
      recommended. Chronic sphenoid lesions may pose a problem of etiologic diagnosis.
      It may be difficult to differentiate between benign and malignant lesions. The
      most common presenting symptom is headache, followed by visual symptoms and
      cranial nerves palsies. Radiographically, computed tomography is the gold
      standard. Treatment includes antibiotic therapy and surgical drainage. This
      drainage is now done through an endoscopic approach.

PMID- 9765713
TI  - [Digital multi-filter auditory prosthesis: study of its efficiency in function of
      number of filters and their programming].
AB  - We designed a prototype of a 7-filter digital auditory prosthesis table
      prototype. For each of these filters frequency band width, amplification and
      compression were programmable in order to adapt these parameters to the deaf
      patient's audiometric particularities. We compared the hearing improvement it was
      possible to obtain either with the 3-analogue-filter auditory prosthesis Triton
      3004 from Siemens, or with our prototype as a function of the number of filters
      (3, 4 or 7) and their frequency band width programmability. We tested 21 patients
      suffering from middle or severe neurosensory hearing loss. This study allows to
      demonstrate that to overpass the present analogue T004 device a 7 programmable
      width-filter strategy seems to be the most appropriate. Further studies
      benefiting with material improvement of our prototype and finer audiometric
      adjustment of filter strategies as well as long term clinical studies have to be
      carried out.

PMID- 9765714
TI  - [Cochlear implant and cerebral dominance].
AB  - On right handed people the right ear is considered to transmit speech
      information, and the left ear musical and cognitive information. These dominating
      ear properties are not exactly symmetrical in the left handed population, and are
      more consistent in females than in males. CI efficacy assessment is strongly
      based on speech intelligibility performances, because these criteria allow to
      measure the social reinsertion and communication possibilities. Consequently, one
      may ask if the relationship of the implanted side and the patient's handness
      could not be an important factor of this CI efficacy. We studied this
      relationship on 71 post-lingually deaf adult implantees. We measured patients
      handness using the Schachter's version of the so called Edimburg questionnaire
      described by Geschwind; this measurement has been moderated to take count of
      ambidextrous and mixed-handed population. Post operative performances has been
      assessed using the Francophone Protocol devoted to adults. We found that there is
      no significant correlation between these post-operative performances and the
      studied relationship. We estimate: 1) This absence of correlation is probably due
      to the high number of data which lead to determine the ear for implanting. 2) As
      far as this choice is feasible, dominating ear must nevertheless be elected, not
      only for theoretical reasons, but because the dominating hand may be easily
      employed for antenna adjustment. 3) As handness is strongly evident only after 4
      y.o., and as left-handness seems to be more frequent on a congenitally deaf
      population, this choice is more problematic on less than 2 y.o. deaf children.

PMID- 9765715
TI  - [Cochlear implant in the aged patient].
AB  - Despite the fact that elderly people live frequently alone and frequently have
      difficulties of vision, is it reasonable to refuse to supply a patient with a
      cochlear implant only because he is too old? We compare the results of 87 post
      lingually implantees as a function of age, less than 60 years (young) and 60
      years or more (old). We assessed the implant efficacy using the Protocole
      Francophone d'Evaluation (PFE), appreciated the speech-therapist's opinion and
      the patient's satisfaction, and counted the number of hours per day the implant
      was used (H/D). The PFE score was significantly higher in young than old. However
      the speech-therapist's opinion and the patient's satisfaction as well as H/D did
      not differ significantly in the 2 series. Elderly people are supplied with a
      great benefit from cochlear implants. Therefore age is not a contraindication for
      implantation.

PMID- 9765716
TI  - [Indications for the cochlear implant in partial deafness of the adult].
AB  - The last (may 1995) NHI Consensus Development Conference on cochlear implant
      recommends to extend the use of cochlear implant for adult patient suffering from
      bilateral acquired severe hearing impairment. Its indications are a severe-to
      profound sensorineural hearing loss bilaterally presenting an open-set sentence
      recognition scores less than or equal to 30 percent under best aided conditions.
      We report the results of our 4 first implantees responding to these criteria, and
      discuss the mechanisms of the speech intelligibility improvement which has been
      obtained.

PMID- 9765717
TI  - [Necessity of auditory and academic supervision in patients with unilateral
      hearing disorder. Retrospective study of 175 children].
AB  - This report reviews a consecutive series of 175 children suffering from
      unilateral hearing loss of 20 dB or more evaluated at the Clocheville Hospital
      between 1980-1991. We found no numerical preponderance of gender nor of side
      impairment. The mean age of diagnosis was 6.9 years. Based on speech frequency
      threshold averages, the loss was profound in 49.7%. 32.8% of the children
      experienced a deterioration of hearing of 10 dB or more. 40.4% of the children
      had repeated a grade during primary school (versus 16.3% in normal hearing
      population, p < 0.001). Monaural deafness especially when more than 40 dB, or
      delayed identification is significantly associated with a grade failure. A
      concerted effort aimed at early identification and management strategies in cases
      of unilateral hearing loss in children is warranted.

PMID- 9765718
TI  - [Peripheral auditory lateralization].
AB  - Neuropsychological studies have demonstrated that language perception is
      lateralized at the hemispheric level. There is also much evidence for a
      peripheral lateralization of the auditory system in humans. Spontaneous
      otoacoustic emissions are more frequent in the right than in the left ear. The
      medial olivo-cochlear system is also more functional in the right than in the
      left ear in normal subjects. The study of specific samples shows that this
      asymmetry is found in professional musicians which have more functional efferent
      system in both ears. A link is hypothesized between peripheral and central
      laterality because of a dysfunctional peripheral asymmetry in pathological cases
      which show hemispheric lateralization disorders. Consequences of those
      pathological data will be discussed.

PMID- 9765719
TI  - [Static balance is controlled by a non-linear dynamic system].
AB  - Different techniques of stabilometric signal analysis have been used in order to
      study the adaptation of the fine postural control system to the wearing of
      corrective glasses with or without prisms. The comparison between the results
      obtained with conventional techniques and those obtained with non-linear dynamic
      methods demonstrates the better efficiency of the latter. These results confirm
      that the postural system behaves as a non-linear dynamical system and may explain
      the outstanding sensitivity of the fine postural system to small perturbations.

PMID- 9765720
TI  - [Bilateral closure of the nasal cavity. An original surgical technique of
      treatment of severe recurrent epistaxis in Rendu-Osler disease].
AB  - In the Rendu Osler disease, epistaxis are seen in 80 to 90% of patients, and the
      multiple treatments that have been proposed have each shown their failure to
      achieve satisfactory results. We propose, in the case of abundant epistaxis, a
      bilateral closure of the nasal cavity. This technique has been initially
      described by Young in 1967 in the treatment of chronic atrophic rhinitis. This
      operation was carried out in two patients who presented with serious daily
      epistaxis, poorly tolerated, and refractory to several treatments. Neither of
      these patients has presented a post-operative bleeding episode with a one year
      and six months follow-up respectively. Anatomically, the results are satisfactory
      in both patients, with total closure of the nasal cavity. Functionally, both
      patients are satisfied, with an appreciable improvement in the quality of life
      despite total nasal obstruction.

PMID- 9765721
TI  - The clinical practice guideline: an evolving health care technology.

PMID- 9765722
TI  - Surgical management of early stage invasive breast cancer (stage I and II).
      Provincial Breast Disease Site Group.
AB  - GUIDELINE QUESTION: What is the optimal surgical management of early stage
      invasive breast cancer (stage I and II)? More specifically, what is the relative
      efficacy (and safety) of breast conservation therapy (lumpectomy with axillary
      dissection) compared with modified radical mastectomy? OBJECTIVE: To make
      recommendations about surgical management and techniques in the treatment of
      early stage invasive breast disease (stage I and II). OUTCOMES: Survival, local
      recurrence (for lumpectomy patients) and quality of life are the primary outcomes
      of interest. PERSPECTIVE (VALUES): Evidence was selected and reviewed by 6
      members of the Ontario Cancer Treatment Practice Guidelines Initiative, Disease
      Site Group for Breast Cancer (Breast DSG). Earlier drafts of this evidence-based
      recommendation have been reviewed, discussed and approved by the Breast DSG,
      which comprises surgeons, medical oncologists, radiation oncologists,
      epidemiologists, a pathologist and a medical sociologist. There was no consumer
      participation in the development of this guideline. QUALITY OF EVIDENCE: There
      are 7 randomized controlled trials (RCTs) comparing breast conservation therapy
      with mastectomy in women with early stage breast cancer. BENEFITS: In 6 RCTs, no
      statistically significant differences were detected in survival rate between the
      mastectomy and conservative therapy (lumpectomy) groups. In 1 RCT, a
      statistically significant differences was detected in favour of the mastectomy
      arm; however, this was an early trial with substantial methodologic weaknesses.
      HARMS: None. PRACTICE GUIDELINE: Women with early stage invasive breast cancer
      (stage I and II) who are candidates for breast conservation therapy (see
      discussion of technical factors) should be offered the choice of either breast
      conservation therapy (excision of tumour with clear margins and axillary
      dissection) or modified radical mastectomy. The choice is an individual one for
      the patient, and thus she should be fully informed of the options, including the
      risks and benefits of each procedure. She should be informed that breast
      irradiation is part of the procedure for breast conservation therapy. In
      addition, she should be aware of the potential need for further surgery if the
      margins are positive. For further information about the use of radiotherapy in
      the management of early stage breast cancer, please refer to the Ontario Cancer
      Treatment Practice Guidelines Initiative's practice guideline Breast Irradiation
      in Women with Early Stage Invasive Breast Cancer Following Breast Conserving
      Surgery.

PMID- 9765723
TI  - Chemotherapy in stage IV (metastatic) non-small-cell lung cancer. Provincial Lung
      Disease Site Group.
AB  - GUIDELINE QUESTION: In patients with metastatic, stage IV non-small-cell lung
      cancer (NSCLC) does chemotherapy improve survival and quality of life? OBJECTIVE:
      To make recommendations about the role of chemotherapy in the treatment of
      metastatic (stage IV) NSCLC. OUTCOMES: Survival and quality of life are the
      primary endpoints of interest. Specifically, 1-year survival will be considered.
      PERSPECTIVE: Evidence was selected and reviewed by 3 medical oncologists and the
      project coordinator of the Ontario Cancer Treatment Practice Guidelines
      Initiative. Drafts of this document have been circulated and reviewed by the
      Provincial Lung Disease Site Group (Lung DSG). The Lung DSG comprises medical and
      radiation oncologists, pathologists, surgeons, epidemiologists, a psychologists
      and a medical sociologist. There was no consumer participation in the development
      of this guideline. QUALITY OF EVIDENCE: There were 3 meta-analyses available for
      review, but only 1 is discussed in detail. The largest and most comprehensive
      meta-analysis is based on 11 randomized controlled trials involving 1190
      patients. The main comparisons were chemotherapy plus supportive care versus
      supportive care alone. The largest trial included in the meta-analysis involved
      randomization of 188 patients, and the smallest trial involved randomization of
      32 patients. Only trials that had accrued patients between Jan. 1, 1965, and Dec.
      31, 1991, were included in the analysis. BENEFITS: A survival benefit at 1 year
      was seen for the group of patients treated with chemotherapy (pooled hazard ratio
      0.84; 95% confidence interval [CI], 0.74 to 0.95). Subgroup analyses suggested a
      benefit for patients receiving chemotherapy regimens containing cisplatin (pooled
      hazard ratio, 0.73; 95% CI, 0.63 to 0.85; relative risk reduction for death, 27%;
      absolute improvement in 1 year survival, 10%; 95% CI, 5% to 18%; gain in median
      survival 1.5 months; 95% CI, 1 to 2.5 months). No benefit for patients treated
      with chemotherapy was found beyond 1 year. None of the randomized trials
      successfully measured quality of life using QOL assessment instruments. No firm
      conclusions can be made about the potential benefits (as measured by quality of
      life) that chemotherapy has for patients with metastatic NSCLC, as there are no
      available data from randomized controlled trials. However, several trials have
      documented relief of cancer-related symptoms, such as pain, cough, hemoptysis or
      dyspnea in the majority (approximately 70%) of patients. HARMS: In a subgroup
      analysis of trials that used long-term alkylating agents other than cisplatin (an
      approach no longer used as therapy in NSCLC) as part of the chemotherapy regimen,
      the meta-analysis demonstrated a detrimental effect of chemotherapy on survival
      (pooled hazard ratio, 1.26; 95% CI, 0.96 to 1.66, p = 0.09). In general,
      myelosuppression, sepsis resulting in hospitalization, drug-specific toxicities
      and death are potential complications of chemotherapy.

PMID- 9765724
TI  - Use of vinorelbine in non-small-cell lung cancer. Provincial Lung Disease Site
      Group.
AB  - GUIDELINE QUESTION: Is there a role for the use of vinorelbine in the treatment
      of patients with non-small-cell lung cancer (NSCLC)? OBJECTIVE: To make
      recommendations about the use of vinorelbine in the management of patients with
      NSCLC. OUTCOMES: Survival is the primary endpoint of interest. Response and
      toxicity are secondary endpoints. PERSPECTIVES: Evidence was selected and
      reviewed by the 4 members of the Lung Disease Site Group (Lung DSG). Early drafts
      of this practice guideline were reviewed by the Lung DSG and by the Systemic
      Treatment Program Committee (STPC). These committees comprise medical and
      radiation oncologists, pathologists, surgeons, epidemiologists, pharmacists,
      nurses, a psychologist, a medical sociologist and administrators. No consumers
      participated in the development of this guideline. QUALITY OF EVIDENCE: Only
      evidence from randomized controlled trials (RCTs) and phase II studies was
      evaluated. Six RCTs and 5 phase II studies were reviewed and are discussed in
      this report. Of the 6 RCTs, 3 have been fully published. BENEFITS: Vinorelbine,
      either as a single agent or in combination with cisplatin, produces higher
      response rates (12%-37%) than other single agent vinca alkaloids (10%-20%) in
      patients with previously untreated NSCLC. Two of 3 RCTs that reported survival
      differences demonstrated a survival benefit for previously untreated patients
      with NSCLC when treated with vinorelbine in combination with cisplatin as
      compared with patients treated with either vindesine plus cisplatin (p = 0.04) or
      leucovorin plus 5-fluorouracil (p = 0.03). The third study reported no
      statistically significant difference between patients treated with vinorelbine
      alone and those receiving vinorelbine plus cisplatin. HARMS: The major toxic
      effects are hematologic. Neutropenia is the dose-limiting toxic effect. However,
      there is less neurotoxicity than with other vinca alkaloids (e.g., vindesine) and
      less nausea and vomiting than with other active agents used in the treatment of
      NSCLC. PRACTICE GUIDELINE: Evidence from randomized controlled trials supports
      the use of vinorelbine as an option for the first-line treatment of patients with
      locally advanced or metastatic NSCLC. Whether vinorelbine is used as a single
      agent or in combination with cisplatin depends on the anticipated trade-offs
      between the expected symptomatic benefits of a higher response rate with the
      combination (as seen in randomized controlled trials) and the increased toxicity.
      Evidence for a possible survival advantage for the combination of vinorelbine and
      cisplatin over vinorelbine alone is conflicting. There is insufficient evidence
      at the present time to advocate the use of vinorelbine in previously treated
      patients who have recurrent or progressive disease. Similarly, there is
      insufficient evidence at the present time to advocate the use of vinorelbine as
      adjuvant or induction therapy for patients with stage I, II or early stage III
      disease. The enrolment of patients with NSCLC in clinical trials is encouraged.

PMID- 9765725
TI  - Canadian perspectives on breast cancer: the challenges for the future.

PMID- 9765726
TI  - Personal experience. Breast cancer survivor.

PMID- 9765727
TI  - The black box: physician response to breast cancer guidelines.

PMID- 9765728
TI  - Silicone-gel-filled breast implants: how they interface with breast cancer. The
      Working Group on Guidelines for Silicone Gel-Filled Breast Implants.

PMID- 9765729
TI  - Tamoxifen and breast cancer prevention: are we aware of the risks?

PMID- 9765730
TI  - Controversies in breast cancer screening.

PMID- 9765731
TI  - Perspectives on Reach to Recovery and CanSurmount: informing the evaluation
      model.
AB  - The Canadian Cancer Society requested that the Centre for Behavioural Research
      and Program Evaluation of the National Cancer Institute of Canada evaluate Reach
      to Recovery and CanSurmount, 1-on-1 peer-support programs that provide
      information and support to individuals with cancer and their families. Key
      informant interviews (with program participants and volunteer visitors) were
      conducted to gather qualitative data and to help us develop a framework and tools
      to evaluate these programs. We found that 1) there are program objectives from
      the perspective of volunteers and participants in addition to those outlined in
      the program materials; 2) there are variations in how the programs are delivered
      and how patients or family members are recruited into the program; and 3) there
      is evidence that Reach to Recovery and CanSurmount volunteers are in a unique
      position to deliver the programs, either because they have personally experienced
      cancer or have family members who have had cancer. We describe the key informant
      exercise developed for this evaluation project and present the results of
      preliminary data-gathering activities.

PMID- 9765732
TI  - Using Reiki to manage pain: a preliminary report.
AB  - The purpose of this study was to explore the usefulness of Reiki as an adjuvant
      to opioid therapy in the management of pain. Since no studies in this area could
      be found, a pilot study was carried out involving 20 volunteers experiencing pain
      at 55 sites for a variety of reasons, including cancer. All Reiki treatments were
      provided by a certified second-degree Reiki therapist. Pain was measured using
      both a visual analogue scale (VAS) and a Likert scale immediately before and
      after the Reiki treatment. Both instruments showed a highly significant (p <
      0.0001) reduction in pain following the Reiki treatment.

PMID- 9765734
TI  - Psychosocial issues and life-cycle concerns of women with breast cancer.

PMID- 9765733
TI  - Admissions to a radiation oncology inpatient service.
AB  - PURPOSE: Although the care of inpatients is an important aspect of radiation
      oncology practice in many countries, it has never been studied in detail. The
      goal of this study was to describe the admissions to a radiation oncology
      inpatient service over a 1-year period with respect to patient characteristics,
      primary malignancies, common nonmalignant diagnoses, use of radiotherapy and
      outcome of admission. METHOD: Using computerized hospital databases, we analysed
      the utilization of 11 radiation oncology beds in a 424-bed teaching hospital from
      March 31, 1991, to April 1, 1992. RESULTS: There were 342 admissions of 277
      patients. The median age was 66.5 years; the male:female ratio was 1:1. The
      commonest primary neoplastic diagnoses were lung (42%), gynecological (15%),
      genitourinary (14%) and breast (8%) cancers. Only 17% of the patients had cancer
      as the sole diagnosis; most patients had multiple medical diagnoses. Infections
      (22%), neurological (20%), cardiovascular (13%) and endocrine (9%) conditions
      were the commonest. Mean length of stay was 11.25 days. Most of the admissions
      (71%) resulted in discharge to the patient's home; few patients (15%) died. Only
      half of admissions involved radiotherapy, indicating that the focus of patient
      care was the medical treatment of cancer complications or other active medical
      problems. CONCLUSION: These data show that radiation oncology inpatients have
      complicated medical problems, and they support the training of radiation
      oncologists in the comprehensive medical care of patients.

PMID- 9765735
TI  - Opportunities for research on prevention of breast cancer.

PMID- 9765736
TI  - Information dissemination, access and informed consent: communications issues
      discussed in the panel sessions of the National Forum on Breast Cancer.

PMID- 9765737
TI  - Laying the groundwork for broadly based partnerships: the perceived influence of
      the National Forum on Breast Cancer.

PMID- 9765738
TI  - Factors associated with the use of mammography: the Ontario Health Survey.

PMID- 9765739
TI  - Interaction between the breast cancer patient and the health care system:
      demands, constraints and options for the future.

PMID- 9765741
TI  - [Cancer of the breast, family functioning and adjustment to the disease].

PMID- 9765740
TI  - Investigations for staging and follow-up of breast cancer patients.

PMID- 9765742
TI  - Methodological problems in the epidemiology of dietary fat and breast cancer.

PMID- 9765743
TI  - Spanning a continuum from cancer prevention amongst the entire healthy population
      to the unique treatment.

PMID- 9765744
TI  - An introduction to the framework project.
AB  - The framework project of the Advisory Committee on Cancer Control (ACOCC),
      National Cancer Institute of Canada (NCIC), was based on the NCIC/ACOCC
      conceptual framework for bridging the gap between research and action. The
      project was carried out under the auspices of the Sociobehavioural Cancer
      Research Network (SCRN) of the NCIC. It focused on 3 research areas of cancer
      control research: smoking control, palliative care and screening for breast
      cancer. In this introductory paper, the criteria and methodology used for the
      framework project are described, the main features of the framework are outlined
      and the definitions of terms used in the framework are summarized. It was
      expected that the framework project would lead to a better understanding of the
      strengths and weaknesses of the NCIC/ACOCC conceptual framework. The project was
      also expected to assist the SCRN in its ongoing efforts to develop and refine an
      action-oriented research agenda.

PMID- 9765745
TI  - School-based smoking control: a research agenda.
AB  - Within the context of a framework for cancer control, this article reviews
      evidence and suggests research directions for 3 types of school-based smoking
      interventions: elementary school prevention, secondary school interventions and
      interventions linking community and school. Directions for smoking research in
      elementary schools include improving adoption through the provision of
      effectiveness criteria, tailoring interventions to schools and training.
      Monitoring at micro and macro levels may help planning and implementation, but
      clearer evidence is required of its feasibility. Fundamental research should
      explore new options to understand why youth do not start smoking. Smoking
      intervention research at the secondary school level is less well established,
      with only 1 effectiveness trial reported. We recommend testing models that
      involve youth in developing their own solutions and examining the interaction of
      various control measures. Sustainability issues have led researchers to embed
      school-based smoking interventions in community-wide activities. Intervention
      research of this sort still needs to determine how to apply approaches (e.g.,
      comprehensive school health) and what the appropriate roles are (such as
      technical assistance) for community agencies. All research using these school
      community approaches needs to include process measures to explain potential
      failures to obtain significant differences between components. In addition, we
      call for research on the training of educators and health personnel, to increase
      the priority given to smoking prevention and improve the implementation of
      existing programs. Research on policy initiatives that lead to effective training
      needs to be explored. Finally, we argue that application of the principles
      incorporated into the cancer control framework (e.g., through participatory
      research methods) strengthens the research process and results.

PMID- 9765746
TI  - Promotion of breast cancer screening in communities: a research agenda.
AB  - This paper used the National Cancer Institute of Canada (NCIC) cancer control
      framework to review research on participation in breast cancer screening programs
      and identify areas for further study. Cancer Lit, MEDLINE, CINAHL, Sociofile,
      Health and the Public Affairs Information Service databases were searched for
      literature published from 1990 to 1995. Information was also obtained from
      provincial breast cancer screening programs and Health Canada. Interventions
      designed to promote participation in screening programs have not been effective.
      Involvement of the target community, however, increased success and
      sustainability. Barriers to initial participation within screening programs
      include alternative sources of screening and the lack of funds to screen all
      eligible women. Studies show that participation decreases with successive
      screening rounds. The priorities for study are development of: a theoretical
      framework for recruitment strategies, a method to capture all Canadian screening
      results including those performed through provincial health insurance plans and a
      mechanism to deliver screening to all eligible Canadian women.

PMID- 9765747
TI  - Focus groups with cancer patients: toward a more comprehensive understanding of
      the cancer experience.
AB  - Six focus groups of 58 individuals (30 women and 28 men) were held in 3 Canadian
      cities to help develop a survey instrument to be implemented nationally to
      identify cancer patients' experiences with cancer: treatment, symptoms and
      symptom management. Patient participants had different cancer diagnoses, but
      their experience with cancer had been within the year preceding the study. Our
      intent was to identify as many themes as possible to allow for comparison of
      different experiences in a national survey. This paper reports on what was
      learned substantively from these focus groups and discusses the methodological
      contribution of focus groups in developing survey tools.

PMID- 9765748
TI  - Breast irradiation in women with early stage invasive breast cancer following
      breast conservation surgery. Provincial Breast Disease Site Group.
AB  - GUIDELINE QUESTIONS: 1) Should breast irradiation be given to women with early
      stage invasive breast cancer (stage I and II) following breast conservation
      surgery (lumpectomy with clear resection margins and axillary dissection)? 2) Is
      there an optimal schedule for breast irradiation? 3) What is a reasonable
      interval between definitive surgery and the start of breast irradiation? 4) Are
      there patients who can be spared breast irradiation after lumpectomy? OBJECTIVE:
      To make recommendations about the use of breast irradiation in women with early
      stage invasive breast cancer following breast conservation surgery. OUTCOMES:
      Local control is the primary endpoint of interest. Survival, quality of life
      (addressed through the adverse effects of radiotherapy) and cosmesis are also
      considered. PERSPECTIVE (VALUES): Evidence was selected and reviewed by 6 members
      of the Breast Disease Site Group (Breast DSG) of the Ontario Cancer Treatment
      Practice Guidelines Initiative. Earlier drafts of the evidence-based
      recommendation were reviewed, discussed and approved by the Breast DSG, which
      comprises medical oncologists, radiation oncologists, surgeons, epidemiologists,
      pathologists and a medical sociologist. There was no participation by a community
      representative in the development of this guideline. QUALITY OF EVIDENCE: There
      are 5 randomized controlled trials (RCTs) and 1 meta-analysis comparing breast
      irradiation with no breast irradiation following breast conservation surgery; 6
      randomized trials comparing breast conservation surgery plus breast irradiation
      with mastectomy are also included, as well as several retrospective studies.
      BENEFITS: All of the 5 RCTs showed a significant decrease in local recurrence
      rates among patients receiving radiotherapy. In the 4 trials with a median follow
      up of 5 years or longer, the relative risk reduction with breast irradiation
      ranged from 69% to 88%. The absolute differences ranged from 16% (p < 0.001) to
      25% (p < 0.001). Despite the effect on local recurrence, no difference in
      survival was detected in any of the 5 trials. Most of the patients with local
      recurrence in these trials underwent mastectomy. HARMS: Major adverse effects of
      breast irradiation occur very infrequently. PRACTICE GUIDELINE: Women with early
      stage invasive breast cancer (stage I and II) who have undergone breast
      conservation surgery should be offered postoperative breast irradiation. The
      optimal fractionation schedule for breast irradiation has not been established,
      and the role of boost irradiation is unclear. Outside of a clinical trial, 2
      commonly used fractionation schedules are suggested: 50 Gy in 25 fractions to the
      whole breast, or 40 Gy in 16 fractions to the whole breast with a local boost to
      the primary site of 12.5 Gy in 5 fractions. Shorter schedules (e.g., 40 or 44 Gy
      in 16 fractions) have also been used routinely in some centres. The enrollment of
      patients in ongoing clinical trials is encouraged. Women who have undergone
      breast conservation surgery should receive local breast irradiation as soon as
      possible after wound healing. A safe interval between surgery and the start of
      radiotherapy is unknown, but it is reasonable to start breast irradiation within
      12 weeks after definitive surgery. For women who are candidates for chemotherapy,
      the optimal sequencing of chemotherapy and breast irradiation is unknown. It is
      reasonable to start radiotherapy after the completion of chemotherapy, or
      concurrently if anthracycline-containing regimens are not used. For further
      information, please refer to Ontario Cancer Treatment Practice Guidelines
      Initiative's practice guideline "Surgical Management of Early Stage Invasive
      Breast Cancer (stage I and II)."

PMID- 9765749
TI  - Erythropoietin in the management of patients with nonhematologic cancer receiving
      chemotherapy. Systemic Treatment Program Committee.
AB  - GUIDELINE QUESTIONS: 1) Does erythropoietin (EPO) reduce the need for transfusion
      of red blood cells in patients receiving chemotherapy for a nonhematologic
      cancer? 2) Does the administration of EPO improve the quality of life of these
      cancer patients? OBJECTIVE: To make recommendations regarding the use of EPO to
      reduce the need for transfusion of red blood cells in patients receiving
      chemotherapy for a nonhematologic cancer. OUTCOMES: First transfusion requirement
      from the start of chemotherapy is the main outcome of interest. Quality of life
      and costs are also considered. PERSPECTIVE (VALUES): Evidence was selected and
      reviewed by 5 members of the Ontario Cancer Treatment Practice Guidelines
      Initiative (OCTPGI) and the Systemic Treatment Program Committee (STPC). Drafts
      of this document have been circulated to and reviewed by members of the STPC. The
      STPC comprises medical oncologists, pharmacists, supportive care personnel and
      administrators. No community representative participated in the development of
      this practice guideline. QUALITY OF EVIDENCE: Eleven randomized controlled trials
      (RCTs), most placebo-controlled, were available for review. A meta-analysis was
      performed with 8 trials that shared a clinically relevant outcome measure. Only 1
      trial assessed quality of life. BENEFITS: The meta-analysis showed a relative
      risk for transfusion among EPO patients of 0.64 (95% confidence interval 0.53
      0.78), which translates into a 36% relative reduction in the proportion of
      patients requiring transfusion (p = 0.00001). Reduction in transfusion
      requirements was similar across strata defined by methodological quality, EPO
      dose, hematologic status, tumour type at trial entry and chemotherapy regimen. In
      the 1 trial that assessed quality of life, EPO was associated with improved
      quality of life. HARMS: Hypertension has been noted rarely in EPO-treated cancer
      patients. The RCTs did not report adverse effects in EPO-treated patients
      compared with control patients during the follow-up period. Long-term adverse
      effects are unknown. EPO is more costly than transfusion, but formal cost
      effectiveness studies are unavailable. PRACTICE GUIDELINE: For patients receiving
      chemotherapy for nonhematologic cancer in whom symptoms of anemia are expected
      and in whom transfusion of red blood cells is not considered an acceptable
      treatment option, EPO can be recommended as a safe, effective treatment
      alternative. The evidence in support of using EPO is stronger for patients
      receiving platinum-based chemotherapy regimens that for those receiving non
      platinum-based regimens. CLINICAL PRACTICE GUIDELINE DATE: Apr. 4, 1997.

PMID- 9765750
TI  - Unresected stage III non-small-cell lung cancer. Provincial Lung Cancer Disease
      Site Group.
AB  - GUIDELINE QUESTIONS: 1) What is the role of different schedules or doses of
      radiotherapy in patients with unresected, clinical or pathological, stage III non
      small-cell lung cancer (NSCLC)? 2) Does chemotherapy combined with radiotherapy
      provide improved survival compared with radiotherapy alone in patients with
      unresected NSCLC? OBJECTIVE: To make recommendations about the role of
      chemotherapy and radiotherapy in the treatment of unresected stage III NSCLC.
      OUTCOMES: Survival is the primary outcome of interest. Quality of life is a
      secondary outcome. PERSPECTIVE (VALUES): Evidence was selected and reviewed by 5
      members of the Provincial Lung Cancer Disease Site Group (Lung DSG) of the
      Ontario Cancer Treatment Practice Guidelines Initiative. The Lung DSG comprises
      medical and radiation oncologists, pathologists, surgeons, epidemiologists, a
      psychologist and a medical sociologist. No community representative participated
      in the development of this guideline. QUALITY OF EVIDENCE: Two meta-analyses were
      available for review. The specific analysis of interest examined the role of
      combined chemotherapy plus radiotherapy v. radiotherapy alone in locally advanced
      disease. The first meta-analysis included combined data from 22 randomized
      controlled (RCTs) involving a total of 3033 patients. The second included
      combined data from 14 RCTs involving a total of 2589 patients. Also reviewed were
      4 RCTs of radiotherapy alone, 1 trial of combined chemotherapy and radiotherapy
      that was not included in the meta-analysis, 4 abstracts of studies of combined
      chemotherapy and radiotherapy, and 4 trials examining the role of
      hyperfractionated radiotherapy. BENEFITS: In the first meta-analysis, an overall
      benefit was detected at 2 years for the use of combined chemotherapy and
      radiotherapy. A hazard ratio of 0.90 (p = 0.006), or a 10% reduction in the risk
      of death, translated into an absolute benefit of 3% at 2 years and 2% at 5 years.
      A subgroup analysis of cisplatin-based chemotherapy plus radiotherapy versus
      radiotherapy alone demonstrated a 13% reduction in the risk of death in the
      combined treatment arm (pooled hazard ratio 0.87, 95% confidence interval [CI]
      0.79-0.96), for an absolute benefit of 4% at 2 years. In the second meta
      analysis, there was a 13% reduction in the risk of death in the combined therapy
      arm at 2 years (pooled relative risk [RR] 0.87, 95% CI 0.81-0.94) and a 17%
      reduction at 3 years (pooled RR 0.83, 95% CI 0.77-0.90). Subgroup analysis of
      cisplatin-based chemotherapy plus radiotherapy versus radiotherapy alone showed
      similar results: a 15% reduction in the risk of death in the combined therapy arm
      at 2 years (pooled RR 0.85, 95% CI 0.79-0.92) and a 19% reduction at 3 years
      (pooled RR 0.81, 95% CI 0.74-0.88). PRACTICE GUIDELINE: For patients with
      unresected stage III NSCLC, the combination of cisplatin-based chemotherapy and
      radical radiotherapy provides a survival benefit compared with radiotherapy
      alone. This guideline is based on high-quality evidence from 2 meta-analyses of
      RCTs. Patients with good performance status (Eastern Cooperative Oncology Group
      [ECOG] 0-1) and minimal weight loss (less than 5% in the preceding 3 months) have
      been shown to have a survival benefit from treatment with combined chemotherapy
      and radiotherapy and should be considered for this type of treatment approach
      (see section V). For these patients, thoracic irradiation of 60 Gy in 30
      fractions over 6 weeks, in combination with cisplatin-based chemotherapy, should
      be recommended as a treatment option. The patient and physician should discuss
      fully the benefits, limitations and toxic effects of therapy. Patients not
      meeting these criteria are not candidates for combined therapy; those
      experiencing symptoms amenable to treatment should receive palliative thoracic
      irradiation. At this time, hyperfractionated radiotherapy is not recommended
      outside of the context of a clinical trial. (ABSTRACT TRUNCATED)

PMID- 9765751
TI  - Increasing demands to consider both the benefits and costs of cancer treatment in
      decision relating to resource allocation.

PMID- 9765752
TI  - A comparison of the costs of paclitaxel and best supportive care in stage IV non
      small-cell lung cancer.
AB  - PURPOSE: To compare the expenditures associated with single-agent paclitaxel
      (Taxol) with those of best supportive care as treatment for stage IV non-small
      cell lung cancer (NSCLC). METHODS: The primary data sets of 2 phase II trials of
      paclitaxel in advanced NSCLC were obtained. Paclitaxel delivery costs were
      estimated at the Ottawa Regional Cancer Centre using the mean paclitaxel dose
      from the 2 phase II trials, 214 mg/m2, a 3-week schedule and a median of 3
      treatment cycles. Data regarding dosage, costs and survival were incorporated
      into the Statistics Canada POpulation HEalth Model (POHEM), which generated
      hypothetical cohorts of patients treated either with best supportive care or
      paclitaxel. The POHEM model assigned diagnostic workup, treatment, disease
      progression and survival characteristics to each of these cohorts and tabulated
      the costs associated with each. RESULTS: The total cost of administering 3 cycles
      of chemotherapy was Can$8143 per patient. The strategy of treating NSCLC patients
      with paclitaxel cost $3375 more per patient than best supportive care. On the
      basis of the difference in survival duration between stage IV patients treated in
      the best supportive care arm of a previous National Cancer Institute of Canada
      trial and those represented in the pooled phase II survival results, the cost per
      life-year saved was $4778. For sensitivity analyses, the days of hospitalization
      for terminal care, number of cycles given and survival benefit produced were
      varied. The sensitivity analysis produced a cost per life-year saved of up to
      $21,377 under the least favourable assumptions. CONCLUSION: If large phase III
      trials confirm the survival benefits observed in the phase II trials, paclitaxel
      can be considered to be a cost-effective agent in the management of advanced
      NSCLC.

PMID- 9765753
TI  - A critical review of research related to family physician-assisted smoking
      cessation interventions.
AB  - A review of family physician-assisted smoking cessation research indicates that
      the family practice setting affords an excellent opportunity to intervene with a
      large proportion of smokers, at a time when they are receptive to health
      promotion messages. Outcome data at 6- and 12-month follow-up intervals indicate
      the value of combining 3 key strategies in achieving optimal results: physician
      advice and support, nicotine replacement therapy, and cognitive-behavioural
      counselling. The authors' review identifies questions that need to be addressed
      in future research: How can barriers to program delivery be overcome in the
      family practice setting? What is the best way to ensure optimal integration of
      the 3 key strategies? Which follow-up intervals are appropriate (e.g., 6 months,
      12 months, 18 months) given the finding that relapse is common and that most
      smokers make several quit attempts before stopping for good?

PMID- 9765754
TI  - Adjuvant therapy for stage III colon cancer after complete resection. Provincial
      Gastrointestinal Disease Site Group.
AB  - GUIDELINE QUESTIONS: Should patients with resected stage III colon cancer receive
      adjuvant therapy? If so, which therapy should be recommended? OBJECTIVE: To make
      recommendations regarding the use of adjuvant therapy in the treatment of
      resected stage III colon cancer. OUTCOMES: Overall survival is the primary
      outcome of interest. Secondary outcomes are disease-free survival and adverse
      effects of the treatment regimens. PERSPECTIVE (VALUES): Evidence was selected
      and reviewed by 4 members of the Gastrointestinal Disease Site Group (GI DSG) of
      the Ontario Cancer Treatment Practice Guidelines Initiative. Earlier drafts of
      the guideline were reviewed, discussed and approved by the GI DSG, which
      comprises medical and radiation oncologists, surgeons and epidemiologists.
      Community representatives did not participate in the development of this
      guideline but will participate in future guidelines development. QUALITY OF
      EVIDENCE: There are 3 meta-analyses, 33 published randomized controlled trials
      (RCTs) and 1 consensus statement. The GI DSG pooled data from 10 of the 33 RCTs
      that allowed for such an analysis. BENEFITS: Two of 3 RCTs reported improved
      survival rates with 5-fluorouracil (5-FU) plus semustine or mitomycin C (MMC)
      compared with no treatment (observation) after surgical resection. Three trials
      reported a benefit in both overall and disease-free survival with 5-FU plus
      levamisole compared with observation after surgery. In 2 trials, levamisole alone
      did not produce a survival benefit compared with observation. One trial reported
      improved disease-free, but not overall, survival rates with oral HCFU (1
      hexylcarbamoyl-5-fluorouracil) compared with observation. In 3 trials of 5-FU
      plus leucovorin, disease-free and overall survival rates were improved compared
      with observation. Nine trials compared portal vein infusion (PVI) of 5-FU with
      observation after surgery. In 2 of the trials, for which data were available for
      stage III patients only, improved overall survival was reported. There was a
      trend in all studies favouring PVI. One trial reported a survival benefit for
      stage III and IV patients who received oral HCFU maintenance therapy for 1 year
      compared with no maintenance therapy. In a trial comparing MMC plus oral HCFU
      with MMC alone, a survival benefit was reported in the combined treatment group;
      however, the stages of cancer were unevenly distributed among the treatment
      groups. Only 1 study tested monoclonal antibody; a benefit was reported for both
      overall and disease-free survival. A meta-analysis of 10 trials comparing
      adjuvant therapy with observation in patients with stage III disease detected a
      significant reduction in the odds ratio (OR) for death (OR 0.69; 95% confidence
      interval [CI] 0.57 to 0.85), with an absolute improvement in survival of 4% to
      13%. When trials were separated according to the type of treatment given, the
      significant ORs were for 5-FU plus either levamisole (OR 0.61; 95% CI 0.46 to
      0.80) or leucovorin (OR 0.51; 95% CI 0.36 to 0.73). Three recently reported
      trials comparing various combinations of 5-FU plus leucovorin, with or without
      levamisole, showed similar improvements in disease-free and overall survival.

PMID- 9765755
TI  - Well-being at the end of life: Part 1. A research agenda for psychosocial and
      spiritual aspects of care from the patient's perspective.
AB  - This article reviews the scientific literature concerning psychosocial and
      spiritual aspects of palliative care for the patient with cancer. It discusses 4
      separate areas: the continuum of care, communication, spiritual and psychological
      issues, and psychotherapeutic and behavioural management of physical symptoms.
      Most of the research could be classified as fundamental according to the Cancer
      Control Framework of the National Cancer Institute of Canada. In some areas, even
      fundamental research was lacking. There is a need for clearer and more relevant
      definitions of the desired outcomes of interventions and also for the development
      of appropriate quantitative and qualitative methods. We must determine which
      interventions can be initiated earlier in the disease trajectory and can provide
      benefit at the palliative phase. Given the burden of suffering that palliative
      care aims to address, relatively little research in this area has been conducted.

PMID- 9765756
TI  - Well-being at the end of life: Part 2. A research agenda for the delivery of care
      from the patient's perspective.
AB  - This article reviews the scientific literature in several areas important to the
      delivery of palliative care: multicultural issues, education, comprehensive
      outcome measures and ethics. Most of the research can be classified as
      fundamental rather than intervention research according to the Cancer Control
      Framework of the National Cancer Institute of Canada. Desired outcomes of
      interventions are most often defined from the health care professional's
      perspective but need to be defined from the patient's perspective. In areas such
      as multicultural issues and the effect of the volunteer on the patient, there is
      almost no research. The complexity of studying the best way to deliver palliative
      care would benefit from the input of colleagues who have experience addressing
      these issues in other patient populations.

PMID- 9765757
TI  - Family health and the palliative care trajectory: a cancer research agenda.
AB  - This article reviews the published literature related to families of palliative
      care patients with cancer within the context of the Cancer Control Framework of
      the National Cancer Institute of Canada. Three themes emerged: 1) the impact of
      terminal cancer on the family; 2) family functioning--responses to terminal
      cancer; and 3) quality of palliative care from the family perspective. The most
      substantial body of research describes family needs, family caregiving burdens,
      caregiving costs and the impact of the patient's terminal cancer on the health of
      family members. Small samples, high nonresponse rates, selection biases and a
      lack of standardized outcome measures have impeded the advancement of knowledge.
      Method development studies are warranted, including the development of
      instruments to measure family care constructs. Longitudinal studies to examine
      the long-term impact of the patient's functional status, mood, symptom distress
      and quality of life on family members are needed. Research should also explore
      the effects of family composition, socioeconomic factors, culture and
      spirituality on families' experiences with terminal illness. Identification of
      families at risk as well as development and rigorous testing of appropriate
      interventions should become priorities.

PMID- 9765758
TI  - Critique of the National Cancer Institute of Canada's framework for cancer
      control.
AB  - This paper offers a critique of the National Cancer Institute of Canada's (NCIC)
      framework for cancer control. The critique has been prepared by researchers who
      used the framework to review the literature in 5 substantive areas. These
      reviews, published in the current and previous issues of CPC, were designed to
      begin to outline a research agenda for the Sociobehavioural Cancer Research
      Network. In this paper, the authors reflect on the strengths and limitations of
      the framework. Perceived strengths are that the framework (a) facilitates
      systematic thinking about research options and priorities, (b) helps foster clear
      communication, (c) links science and practice, (d) may assist grant review panels
      to place proposed studies in context and (e) emphasizes important values.
      Perceived concerns include the following: (a) potential users are not familiar
      with the framework, (b) lack of clarity of definitions and classification
      criteria, (c) the utility of the framework is not immediately self-evident to
      potential users, (d) the framework lacks emphasis on environmental and policy
      interventions and (e) it is not clear how the values espoused are to be
      integrated with other dimensions of the framework. The concerns were seen as
      remediable. In short, the framework was seen to be valuable in its current form;
      refinement may enhance its value.

PMID- 9765759
TI  - Adjuvant radiotherapy and chemotherapy for stage II or IIIA non-small-cell lung
      cancer after complete resection. Provincial Lung Cancer Disease Site Group.
AB  - GUIDELINE QUESTIONS: 1) Does the use of postoperative, adjuvant radiotherapy or
      chemotherapy, alone or in combination, improve survival rates among patients with
      completely resected, pathologically confirmed stage II or IIIA non-small-cell
      lung cancer (NSCLC)? 2) Does the use of radiotherapy reduce the risk of local
      recurrence among patients with completely resected stage II or IIIA NSCLC?
      OBJECTIVE: To make recommendations about the use of postoperative adjuvant
      radiotherapy and chemotherapy in the treatment of patients with completely
      resected stage II or IIIA NSCLC. OUTCOMES: Overall survival and disease-free
      survival are the primary outcomes of interest. A secondary outcome of interest is
      local disease control. PERSPECTIVES (VALUES): Evidence was collected and reviewed
      by 4 members of the Lung Cancer Disease Site Group (Lung Cancer DSG) of the
      Cancer Care Ontario Practice Guidelines Initiative. The evidence-based
      recommendation resulting from this review was approved by the Lung Cancer DSG,
      which comprises medical oncologists, radiation oncologists, pathologists,
      surgeons and a medical sociologist. A community representative was present at 1
      meeting during which the recommendation was discussed. QUALITY OF EVIDENCE: One
      meta-analysis and 22 randomized controlled trials (RCTs) were published between
      1962 and 1996. The RCTs compared surgery plus radiotherapy with surgery alone;
      surgery plus adjuvant chemotherapy with surgery alone; surgery plus radiotherapy
      with surgery plus both chemotherapy and radiotherapy. Many studies included
      patients with stage IIIB NSCLC; some included patients with incompletely resected
      stage I NSCLC or with small cell lung cancer (maximum 10%). Older studies used
      chemotherapy or radiation that would now be considered inferior according to
      current standards of practice. BENEFITS: There was no survival benefit with
      adjuvant radiotherapy alone, although 3 RCTs reported a reduction in the rate of
      local recurrence among patients treated with adjuvant radiotherapy. The meta
      analysis showed that postoperative, cisplatin-based chemotherapy alone reduced
      the relative risk of death by 13% (hazard ratio [HR] 0.87, 95% confidence
      interval [CI] 0.74 to 1.02); in combination with radiotherapy it resulted in a 6%
      reduction in the relative risk of death (HR 0.94, 95% CI 0.79 to 1.11). HARMS:
      Postoperative adjuvant chemotherapy with alkylating agents was found in the meta
      analysis to increase the relative risk of death by 15%. A study involving
      prolonged adjuvant chemotherapy (busulfan or cytoxan daily for 2 years) reported
      that 4 of 726 patients had hematologic malignancies. In 1 study, only 53% of
      patients received all 4 cycles of chemotherapy with cyclophosphamide-doxorubicin
      cisplatin (CAP); in another, 22% of patients refused therapy with CAP because of
      nausea and vomiting. PRACTICE GUIDELINE: There is evidence from RCTs that
      postoperative radiotherapy reduces rates of local recurrence by 11% to 18% (or
      1.6 to 19-fold) among patients with completely resected, pathologically confirmed
      stage II or IIIA NSCLC. Therefore, if the outcome of interest is a reduction in
      the frequency of local tumour recurrence, radiotherapy is recommended. However,
      there is no evidence of a survival benefit from postoperative radiotherapy alone.
      In a meta-analysis, postoperative chemotherapy with or without radiotherapy
      resulted in a slightly reduced (statistically nonsignificant) risk of death among
      patients with surgically resected stage II or IIIA NSCLC. The survival benefit
      was small and achieved only with chemotherapy regimens that produced substantial
      toxic effects and that are no longer used. Newer chemotherapy regimens are
      currently being evaluated as adjuvant therapy, but there is insufficient evidence
      of benefit at this time to recommend them. Therefore, if the outcome of interest
      is survival, there is insufficient evidence to recommend current chemotherapy
      regimens with or without radiotherapy as postoperative, adjuvant the

PMID- 9765760
TI  - Adjuvant therapy for stage II colon cancer after complete resection. Provincial
      Gastrointestinal Disease Site Group.
AB  - GUIDELINE QUESTION: Should patients with resected stage II colon cancer receive
      adjuvant therapy? OBJECTIVE: To make recommendations regarding the use of
      adjuvant therapy in the treatment of resected stage II colon cancer. OUTCOMES:
      Overall survival is the primary outcome of interest. Secondary outcomes are
      disease-free survival and adverse effects of the treatment regimens. PERSPECTIVE
      (VALUES): Evidence was selected and reviewed by 2 members of the Provincial
      Gastrointestinal Disease Site Group (GI DSG) of the Cancer Care Ontario Practice
      Guidelines Initiative. The recommendations resulting from this review have been
      approved by the GI DSG, which comprise medical and radiation oncologists,
      surgeons and epidemiologists. Community representatives did not participate in
      the development of this practice guideline but will do so in future guidelines
      development. QUALITY OF EVIDENCE: There are 25 published randomized controlled
      trials (RCTs) and 1 meta-analysis. The GI DSG pooled data from 11 of the 25 RCTs
      that provided adequate data. BENEFITS: The 25 RCTs are grouped according to the
      type of therapy and whether the control patients received no treatment
      (observation) or other adjuvant therapy after resection. Because the trials
      usually included patients with stage II and III cancer, the complete trial
      results and those for a subset of patients with stage II disease were analysed.
      Although the overall trial results showed a survival benefit for adjuvant
      treatments, the benefit was not significant for stage II patients. A meta
      analysis of 11 trials comparing adjuvant treatment with observation in patients
      with stage II cancer indicated no significant reduction in the odds ratio (OR)
      for death (OR 0.83; 95% confidence interval [CI] 0.62 to 1.10). The OR for death
      among patients receiving chemotherapy by portal vein infusion (PVI) was 0.62 (95%
      CI 0.35 to 1.11). HARMS: The toxic effects of 5-fluorouracil (5-FU) with either
      levamisole or leucovorin, or both, were mild to moderate and consisted mostly of
      stomatitis, diarrhea and myelosuppression; 5% of patients required hospital
      admission. 5-FU plus levamisole was associated with transient neurotoxic effects
      in 18% of patients. Toxic effects associated with PVI were mild, rare and mostly
      consisted of leukopenia and diarrhea; 1% of patients experienced bowel
      perforation. PRACTICE GUIDELINE: Adjuvant therapy is not recommended at this time
      for the routine management of patients with resected stage II colon cancer.
      Patients with stage II disease and high-risk factors (bowel obstruction, tumour
      adhesion, invasion, perforation or aneuploidy) have a poorer prognosis, similar
      to that of patients with stage III colon cancer. For individual management, these
      patients should be made aware of their prognosis; treatment can be considered
      after the uncertainty of the value of adjuvant therapy has been explained to the
      patient. The enrolment of patients with high-risk stage II disease in clinical
      trials is encouraged. Trials comparing adjuvant therapy with observation are
      needed and are ethically acceptable in stage II colon cancer.

PMID- 9765761
TI  - Critical review of 5 nonpharmacologic strategies for managing cancer pain.
AB  - PURPOSE: Health care professionals at 2 Ontario cancer centres were surveyed to
      determine their familiarity with, perceptions of and interest in learning more
      about nonpharmacologic strategies for the management of cancer pain. Evidence
      based education sessions were subsequently developed for the 5 strategies in
      which participants were most interested. This article presents the results of
      critical literature reviews concerning the effectiveness of the 5 strategies:
      acupuncture, massage therapy, hypnosis, therapeutic touch and biofeedback.
      METHODS: The databases MEDLINE (1966 to June 1997), CINAHL (1982 to June 1997)
      and PsychoINFO Lit (1980 to June 1997) were searched systematically for
      randomized controlled trials (RCTs) of the 5 nonpharmacologic strategies. The
      authors' personal files and reference lists of relevant papers and main texts
      were also searched. The quality of the trials was reviewed according to
      established criteria. RESULTS: The search yielded 1 RCT of acupuncture, 1 of
      massage therapy and 6 of hypnosis. The studies of hypnosis suggested that there
      is much support for its use in the management of cancer pain. The evidence was
      either lacking or less clear for the other therapies examined. CONCLUSION:
      Because patients use a wide variety of nonpharmacologic strategies regardless of
      their effectiveness, clinicians need to be familiar with available research and
      able to discuss those strategies for which the evidence is strong, weak or
      nonexistent. More research on the effectiveness of nonpharmacologic strategies
      for pain management is needed.

PMID- 9765763
TI  - Atlantic Breast Cancer Information Project: formation of a "town-gown"
      partnership.
AB  - The Atlantic Breast Cancer Information Project (ABCIP) is one of 5 breast cancer
      information exchange projects funded by Health Canada. This article describes the
      development of ABCIP and thereby contributes to the limited knowledge on
      successful partnership formation in the face of restraints but with support from
      enabling factors. Partnership formation is presented in the context of alliances
      in management, coalitions in health promotion, and social movements. The
      restraining factors were the inertia of the status quo, provincial structures and
      concerns about empowering others. The enabling factors fell into 3 categories:
      timely logistics, roles of individuals who participated at critical points in the
      process, and the evolution of a supportive cultural environment. The article
      outlines ABCIP's achievements to date.

PMID- 9765762
TI  - Survival rates among Canadian children and teenagers with cancer diagnosed
      between 1985 and 1988.
AB  - PURPOSE: To describe the survival rates among Canadian children and teenagers
      with cancer diagnosed between 1985 and 1988 using population-based data,
      specifically for the more common forms of childhood cancer, and to assess the
      effect of age at diagnosis and sex as prognostic factors for selected childhood
      cancers. DESIGN: Retrospective survival study based on incident cases of cancer
      identified by the National Cancer Incidence Reporting System and follow-up
      ascertained by computer record linkage to the Canadian Mortality Database.
      SUBJECTS: A total of 4409 patients with cancer first diagnosed at 19 years of age
      or younger between 1985 and 1988, and followed up to Dec. 31, 1991. MAIN OUTCOME
      MEASURES: Survival rates calculated at 1, 3 and 5 years according to the
      actuarial life table and the proportional hazards models. RESULTS: The 5-year
      survival rate for all cancers combined was 71%. Females with acute lymphoblastic
      leukemia and astrocytoma had markedly higher survival rates than their male
      counterparts (p < 0.05). Age at diagnosis was a significant predictor of survival
      among children with acute lymphoblastic leukemia or acute nonlymphoblastic
      leukemia (p < 0.01), infants having a substantially poorer prognosis than older
      children. Conversely, the survival rate among infants with neuroblastoma was
      higher than that among older children, 87% surviving for 5 years after diagnosis.
      CONCLUSIONS: The survival rate among Canadian children and teenagers with cancer
      is favourable in relation to the rate among adults with cancer. Nonetheless, the
      5-year survival rates for several childhood cancers remain poor (i.e., less than
      65%). The survival rates among Canadian children with cancer are similar to those
      among children with cancer in other developed countries.

PMID- 9765765
TI  - Information needs of women with metastatic breast cancer.
AB  - Eight focus groups involving women with metastatic breast cancer were held across
      Ontario over approximately 6 months in 1996-97. Prevalent themes identified
      during the sessions are reported under 2 broad dimensions: the women's expressed
      desire for information in specific content areas, and issues related to whether
      information can be either beneficial or harmful, depending on how it is provided.
      The women reported high needs for information, especially that which would relate
      to their situation. Perceived adequacy of information is closely linked to health
      professional engagement and care. Although the provision of information is
      important, the needs of these women for maintenance of hope and provision of
      interpersonal support and comfort are also critical.

PMID- 9765764
TI  - Use of preoperative chemotherapy with or without postoperative radiotherapy in
      technically resectable stage IIIA non-small-cell lung cancer. Provincial Lung
      Cancer Disease Site Group.
AB  - GUIDELINE QUESTION: Should preoperative (neoadjuvant) cisplatin-based
      chemotherapy with or without postoperative radiotherapy be offered to patients
      with technically resectable stage IIIA non-small-cell lung cancer (NSCLC) to
      improve survival? (Resectability should be determined preoperatively by a
      thoracic surgeon.) OBJECTIVE: To make recommendations about the use of
      preoperative cisplatin-based chemotherapy with or without postoperative
      radiotherapy in technically resectable stage IIIA NSCLC. OUTCOMES: Survival is
      the primary outcome of interest. PERSPECTIVES (VALUES): Evidence was collected
      and reviewed by 4 members of the Lung Cancer Disease Site Group (LCDSG) of the
      Cancer Care Ontario Practice Guidelines Initiative. The evidence was then
      presented to the full LCDSG and discussed extensively at 5 of its meetings. The
      LCDSG comprises medical and radiation oncologists, pathologists, surgeons,
      epidemiologists, a psychologist and a medical sociologist. A community
      representative was present at one meeting during which the recommendation was
      discussed. QUALITY OF EVIDENCE: Four small randomized controlled trials (RCTs)
      were available for review; 2 were completed and were reported in full in the
      literature, 1 was published in abstract form, and 1 was closed and was reported
      as an interim analysis. Although the RCTs used appropriate clinical trials
      methodology, including planned interim analyses and early stopping rules,
      retrospective review revealed inconsistencies between the treatment arms for
      subsets of stage IIIA disease and for prognostic factors. These factors and the
      small samples in each study limit the interpretation of the results. BENEFITS:
      The data from 2 of the 4 trials were not combined because the data were not
      mature in one case and not extractable in the other. The 2 fully published,
      completed trials reported a survival benefit for patients treated with
      preoperative chemotherapy with or without postoperative radiotherapy compared
      with those not given preoperative chemotherapy. One trial reported a median
      survival of 26 months in the treatment group versus 8 months in the control group
      (p < 0.001). A second trial reported an estimated median survival of 64 months
      versus 11 months (p < 0.008) and a 3-year survival rate of 56% versus 15%
      respectively. A pooled analysis of the 2-year survival data from the 2 completed
      RCTs yielded an odds ratio for death of 0.18 (95% confidence interval 0.06 to
      0.51) in favour of preoperative chemotherapy. HARMS: There was no difference in
      the postoperative mortality between the trials reviewed. Toxic effects associated
      with the chemotherapy were limited primarily to neutropenic fever, nausea and
      vomiting.

PMID- 9765766
TI  - Follow-up practices for patients with early stage breast cancer: a survey of
      Canadian oncologists.
AB  - The value of routine follow-up programs for patients with early stage breast
      cancer remains an area of controversy. In recent years, the cost-effectiveness of
      routine investigations has been questioned, and 2 prospective randomized clinical
      trials have shown no survival advantage to more intensive diagnostic follow-up
      approaches. Under the auspices of the Ottawa Regional Cancer Centre, a national
      survey of the practice patterns of Canadian surgical, radiation and medical
      oncologists was undertaken to measure current Canadian standards of care and to
      determine average costs of 5-year follow-up for patients completing primary
      treatment for stage I and II breast cancer. Standardized questionnaires were sent
      out to 130 surgeons, 59 radiation oncologists and 89 medical oncologists. The
      overall response rate was 44%. Based on the frequency of follow-up visits and
      investigations recommended by respondents, an average cost per patient for a 5
      year follow-up plan was derived for each subspecialist group: $791, $911 and $904
      for surgeons, radiation oncologists and medical oncologists respectively. Use of
      a less interventionist follow-up program was estimated to result in a cost saving
      of $300 per patient over 5 years. The results indicate that, for the most part,
      Canadian oncologists have been influenced by the available literature concerning
      follow-up practices and are ordering fewer routine tests. Further cost savings to
      the Canadian health care system could be achieved with the adoption of even less
      interventionist follow-up programs.

PMID- 9765767
TI  - Effectiveness of megestrol acetate in patients with advanced cancer: a
      randomized, double-blind, crossover study.
AB  - PURPOSE: To evaluate the effect of megestrol acetate at a lower dose than
      previously investigated on the symptoms of cachexia in patients with advanced
      cancer. METHODS: A total of 84 patients with advanced, solid tumours not
      responsive to hormone therapy were enrolled in this double-blind, crossover
      study. During phase 1, patients were randomly assigned to receive megestrol
      acetate (160 mg 3 times daily) for 10 days or placebo. During phase 2, after a 2
      day washout period, patients received the alternate treatment for 10 days.
      Patients underwent daily assessments of activity, nausea, appetite and well-being
      by means of a visual analogue scale (VAS). In addition, nutritional status
      (weight, tricep skinfold measure, arm muscle circumference), energy intake,
      fatigue (Piper Fatigue Scale) and quality of life (Functional Living Index-Cancer
      [FLIC]) were assessed. RESULTS: Among the 53 evaluable patients megestrol acetate
      resulted in a significant improvement in appetite (p = 0.005), activity (p =
      0.007) and well-being (p = 0.03). There was no significant change in the
      intensity of nausea, nutritional parameters, energy intake or FLIC scores. There
      was a significant improvement in 2 of the 3 factors measured by the Piper Fatigue
      Scale and in the overall fatigue score. Upon completion of the study, while still
      blind to the treatment condition, 30 patients indicated that they felt better
      overall after megestrol, 15 said they felt better after placebo, and 10 indicated
      no preference (p = 0.001). CONCLUSION: Treatment with megestrol acetate results
      in rapid and significant improvement of symptoms in terminally ill patients at
      lower doses than previously reported. The effects are not secondary to
      nutritional changes. The FLIC quality-of-life questionnaire was unable to detect
      these changes.

PMID- 9765768
TI  - Use of strontium-89 in endocrine-refractory prostate cancer metastatic to bone.
      Provincial Genitourinary Cancer Disease Site Group.
AB  - GUIDELINE QUESTION: What is the role of strontium-89 in effective palliative care
      of patients with stage D endocrine-refractory prostate cancer and multiple sites
      of painful bone metastases? OBJECTIVE: To make recommendations about the routine
      use of 89Sr in this clinical setting. OUTCOMES: Effective palliation is the
      primary outcome of interest. Patient survival and toxic effects of treatment are
      also considered. PERSPECTIVE (VALUES): Evidence was selected and reviewed by 3
      members of the Genitourinary Cancer Disease Site Group (Genitourinary Cancer DSG)
      of the Cancer Care Ontario Practice Guidelines Initiative. Earlier drafts of the
      guideline were circulated and reviewed by members of the DSG. The Genitourinary
      Cancer DSG comprises medical oncologists, radiation oncologists, urologists, a
      pathologist and a community representative. Guideline approval requires input
      from community representatives. QUALITY OF EVIDENCE: Three randomized controlled
      trials (RCTs) were available for evaluation. Two compared 89Sr with placebo, and
      one RCT compared 89Sr with conventional radiation (either hemibody or involved
      field radiotherapy, as determined before randomization). BENEFITS: One of the 2
      studies comparing 89Sr with placebo demonstrated the palliative efficacy of the
      intervention (p < 0.01); the other showed no benefit. The third study, comparing
      89Sr with conventional radiation, concluded that all treatments provided equally
      effective pain relief and that improvement was sustained for at least 3 months in
      similar proportions of patients. The difference in the median duration of patient
      survival between groups in this study was neither clinically nor statistically
      significant. HARMS: The use of 89Sr may cause bone marrow suppression, but
      clinically significant sequelae are uncommon. The use of 89Sr may preclude
      further systemic chemotherapy or eligibility for clinical trials of systemic
      therapy. Symptoms other than those due to bone marrow suppression are rare.
      PRACTICE GUIDELINE: 89Sr is recommended for use in patients with endocrine
      refractory prostate cancer who have multiple uncontrolled painful sites of bone
      metastases on both sides of the diaphragm not adequately controlled with
      conventional analgesic therapy, and in whom the use of multiple single fields of
      external beam radiation is not possible. 89Sr has proven to be efficacious in the
      palliation of hormone-refractory painful bone metastases from prostate cancer. It
      has not been shown to lengthen the average duration of patient survival. There is
      limited evidence on the relative efficacy of 89Sr compared with wide-field
      radiotherapy. 89Sr is the treatment of choice given all the following specific
      indications: Established diagnosis of prostate cancer metastatic to bone.
      Metastatic disease refractory to hormone therapy. Progressive sites of pain
      poorly controlled with conventional narcotics. Painful sites of disease on both
      sides of the diaphragm (otherwise, hemibody radiotherapy is equally efficacious).
      Patient or tumour factors (number of involved sites, location of involved sites
      or level of pain control) that are relative contraindications to the use of
      multiple single fields of radiation as an alternative. No evidence of impending
      spinal cord compression. Adequate bone marrow reserve. Evidence from a diagnostic
      bone scan of radionuclide concentration in painful bone lesions. PRACTICE
      GUIDELINE DATE: Nov. 23, 1997. Part 2. GUIDELINE QUESTION: What is the role of
      89Sr in effective palliative care of patients with stage D hormone-refractory
      prostate cancer receiving involved-field radiotherapy for isolated painful bone
      metastases? OBJECTIVE: To make recommendations about the routine use of 89Sr in
      this clinical setting. OUTCOMES: Effective palliation is the primary outcome of
      interest. Patient survival and toxic effects of treatment are also considered.
      PERSPECTIVE (VALUES): As described in preceding abstract (Part 1). QUALITY OF
      EVIDENCE: One RCT was available for evaluati

PMID- 9765769
TI  - [Continent urostomy: sigmoid reservoir and sigmoid hydraulic valve].
AB  - We report our experience of continent sigmoidostomy. The technique consisted in
      urinary diversion with sigmoid pouch and hydraulic valve. Eleven patients
      underwent this procedure (10 men and 1 women, mean age 48 years, range 20 to 77
      years). Indications were bladder tumor in 7 cases, bladder exstrophy in 2
      patients, neurogenic bladder in 1 case and 1 bladder with a small capacity
      secondary to a stricture of traumatic urethra. The pouch was made according to
      the detubularized model. The sigmoid was opened on its antimesenteric edge,
      leaving the distal portion of the sigmoid intended to do the sigmoid valve. The
      posterior edges of the colonic segment opened were alined then secured by a Dexon
      3/0 whipping then the anterior adges were secured, as the former after
      reimplantation of the ureters according to Camey Leduc or Politano Leadbetter's
      procedure. The post operative follow-up was marked by a fistula of the pouch in
      one case treated by securing it. All the patients were continent day and night.
      The purpose of this study was the description of the technique and the results of
      the continent sigmoidostomy.

PMID- 9765770
TI  - [Salvage therapy with anti-IL-2 receptor antibodies in high-risk kidney
      transplant patients].

PMID- 9765771
TI  - [Urethral lengthening (the Kropp technic) in neurologic urinary incontinence in
      children and adolescents. Results of a series of 22 cases].
AB  - In 1986 Kropp et Angwafo described a technique of urethral lengthening for the
      treatment of urinary incontinence in children with neurogenic bladders. We have
      used a modified version of this procedure in 22 girls between 1986 and 1990. Here
      we report its mid and long term effects on continence. The problems we have
      encountered in these patients are discussed.

PMID- 9765772
TI  - [Suburethral sling urethropexy: a vaginal approach].
AB  - Considering the poor long term results with the bladder neck suspensions, the
      poor results with the retropubic approach in obese or intrinsic sphincter
      deficiency and the complexity of the classical retropubic sling procedure, a
      simple vaginal sling urethropexy approach was developed. The vaginal mucosa is
      opened at 12 o'clock under the urethra. Dissection of the endopelvic fascia is
      undertaken. Polypropylene sutures are placed at the 4 corners of a free 2 x 4 cm
      rectus abdominis muscle flap which is suspended under the bladder neck
      transvaginally. Polypropylene sutures are tied at the rectus muscle through a 3
      cm suprapubic incision. 25 patients were operated by one single surgeon. 7 had
      previous uretropexies. Previous hysterectomies: 8. Average age: 57. Average
      weight: 67.6. Severe stress incontinence was demonstrated in 23 patients. 9
      patients had mixed incontinence. Average protective pads per day pre-op: 4.1. OR
      time: 93.8 min. Blood loss was minimal. 10 patients had transient post op
      retention (24 days average). 1 bladder perforation. 2 incisional hernias. 6
      suprapubic wound infections. Average hospital stay: 5.95 days. The average follow
      up was 22 months. All patients were either cured (76%) or improved. 73% were
      satisfied (questionnaire). Despite a longer OR time, and the incidence of
      transient post op retention, this vaginal sling urethropexy approach is a simple
      and efficient procedure. It can be useful in previously operated or obese
      patients. It is easier to perform than the more conventional retropubic or
      combined (retropubic and vaginal) sling urethropexy.

PMID- 9765773
TI  - [Attempted classification of scrotal contusions].
AB  - We present a review of the literature and results of a survey involving 50 closed
      scrotal traumas. Based on this analysis, we propose an anatomoclinical
      classification of scrotal contusions based on what we consider to be the most
      appropriate therapeutic management.

PMID- 9765774
TI  - [The renal arterial pedicle in the human fetus].
AB  - To analyze the incidence of renal arteries variations during the fetal period and
      compare these findings with previous findings in adults, we studied the renal
      arterial pedicle in 70 human fetuses ranging in age from 13 to 36 weeks
      postconception. The fetuses were injected through the right common carotid artery
      with a red polyester resin to fill in the arterial tree enabling the
      identification and dissection of the small fetal arteries. The renal arteries
      were analyzed considering their number, origin, direction and site of
      penetration. Among the 70 fetuses studied, 30 (42.8%) presented at least one
      kidney with renal artery variations. In 6 fetuses the variation was bilateral.
      Among the total of 140 renal pedicles studied, 36 presented arterial variations
      (25.7%). We did not find statistically significant difference between right and
      left kidneys and between male and female fetuses. In the present study we did
      find kidneys with more than 2 arteries, probably because we did not study kidneys
      with any kind of development anomaly. Even kidneys with malrotations of the
      vertical axis were removed from the study.

PMID- 9765775
TI  - [Diagnosis of bladder neck obstruction in women].
AB  - Bladder outlet obstruction in women is a rare entity, and difficult to diagnose.
      In our series most of the patients had previous history of gyneco-obstetric or
      urological procedures. Cystometry enabled us to diagnose the coexistence of
      bladder instability and obstruction in 48% of the patients. We did not find
      statistically significant differences between the patients with and without BI in
      terms of degree of obstruction measured by uroflowmetry and pressure/flow
      studies. Pressure/flow studies and Uroflowmetry had been the essential key in the
      diagnosis of obstruction in our series. Cysto-urethrography and urethroscopy were
      normal in over 50% of patients. The urethral calibration was abnormal in 16% of
      the cases.

PMID- 9765776
TI  - [Gangrene of the external genital organs. Apropos of 55 cases].
AB  - Gangrene of the male external genitalia (GMEG) is characterized by necrotizing
      cell evolving toward necrotizing of the soft tissues of the male genitalia and
      possibly death. The cause may be primary infection called Fournier's gangrene
      (5%) or secondary infection (95%) due to general or local factors. GMEG is a real
      urinary emergency because of its local and general complications which lead to
      death in 20% of cases. Precocious and massive antibiotherapy, a surgery to
      unbridle and possibly reanimation, oxygenotherapy, urinary diversion or
      colostomy, are required. We have treated 55 men with this affection from january
      1988 to may 1996. Mean age was 58 years (range 20 to 85). The prodromial period
      was about 12 days. Toxi-infectious shock was noted in 8 patients (14%). Six
      patients (10%) developed renal acute insufficiency. Lesions were localized to the
      male external genitalia in 24 cases and stretched to the inguinalis, to the
      abdomen or to the thorax in 34 patients. The cause was a stricture of urethra in
      23 cases (41%) diabetes in 18 cases (32%), anal abscess in 7 cases (13%). No
      etiology was found in 6 cases (10%). Emergency treatment involved three
      antibiotics, surgery to unbridle necrotizing tissue in all patients, reanimation
      in 20 patients (35%), oxygenotherapy in 4 patients (7%), colostomy in 2 cases and
      urinary drainage in 23 patients (42%). Free skins grafts were necessary in 6
      patients (10%), 5 patients (9%) died due to septic shock. On the basis of these
      observations and a review of the literature, we analyzed the ethiopathogenic,
      bacteriological and therapeutic aspects of this affection marked by high
      mortality in spite of therapeutic progress.

PMID- 9765777
TI  - [Fournier's gangrene. Analysis of 32 cases].
AB  - A series of 32 treated cases of Fournier's gangrene is analysed. All patients
      were male, their age ranged from 19 to 89 years. In 16 cases (50%) the aetiology
      of gangrene was urethral (37.5%), anorectal (12.5%) and in the 16 remaining cases
      (50%) there was no identifiable cause. Mortality was high (28%) despite broad
      spectrum antibiotics and aggressive surgical debridement. This mortality was
      essentially associated to advanced age, debilitated state, delay in diagnosis and
      toxi infectious context. The average hospital stay was 26.5 days.

PMID- 9765778
TI  - [Urinary calculi and indinavir sulfate in patients with HIV infection. Apropos of
      4 cases].
AB  - We report on 4 cases of urinary stone observed in patients treated with the drug
      Crixivan (Indinavir Sulfate) and review the literature. Comments include stone
      composition, clinical aspects, treatment and prevention.

PMID- 9765779
TI  - [Retroperitoneal liposarcoma. Apropos of 2 cases].
AB  - We report two cases of retroperitoneal liposarcoma that required multiple
      surgical excisions for locoregional relapse diagnosed by surveillance based on CT
      scan. One patient has had adjuvant radiotherapy. With the literature review, we
      discuss the pathologic and therapeutic aspects of these lesions.

PMID- 9765780
TI  - [Cysts of the prostate. Apropos of 2 cases].
AB  - Two prostatic cysts have been diagnosed by us since 1993. The first patient
      presented with dysurial the second cyst was discovered incidentally. Transrectal
      ultrasound examination was useful for diagnosis. Treatment was a puncture-
      aspiration of the cyst in the first case, and abstention in the second one. A
      review, of the epidemiological, pathological and therapeutic aspects of the
      prostatic cysts is presented.

PMID- 9765781
TI  - [Acute urine retention. Another presentation of a hydatid cyst of the kidney].
AB  - We report on a case of hydatic cyst of the kidney, in a 12 year-old male,
      revealed by an acute urinary retention. After a brief report of the common signs
      of this parasitic disease, we emphasize the importance of hydaturia and acute
      urinary retention as another revealing sign of this disease.

PMID- 9765782
TI  - [A case of unrecognized bladder pheochromocytoma].
AB  - Pheochromocytoma rarely occurs in the bladder. We report a fortuitously observed
      case and review the main clinical, biological and radiological features.

PMID- 9765783
TI  - [Urethral polyps in children: an unusual cause of obstruction of the lower
      urinary tract].
AB  - We report an unusual case of urethra polyp in a young child which caused
      obstruction of the lower urinary tract. Endoscopy was successful.

PMID- 9765784
TI  - [Bilateral testicular metastasis of cancer of the prostate].
AB  - Testicular metastasis of prostate cancer rarely occurs. Bilateral localization is
      exceptional. We report a new case of prostate adenocarcinoma with bilateral
      testicular metastasis. The diagnosis was made on clinical and ultrasonic
      arguments, and confirmed on the pathological specimen. Treatment consisted in a
      bilateral orchidectomy, associated with nonsteroid androgens.

PMID- 9765785
TI  - [Spermatocytic seminoma. Apropos of a case and review of the literature].
AB  - We report a case of sperm cell seminoma caused by trauma. The data in the
      literature indicate the frequency is less than 5% of all seminomas. This case was
      exclusively located in the gonads and was a pure form. Orchidectomy with high
      ligature of the cord and adjuvant radiotherapy at the dose of 25 Gy centered on
      the para-aortic and subdiaphragmatic chains is adequate treatment. When
      inguinoscrotal surgery is performed, this zone must be irradiated with 25 Gy.
      Prognosis is satisfactory: 5-year survival is 100% with this protocol.

PMID- 9765786
TI  - [Urachal remnants: excision or surveillance? Apropos of 3 cases and review of the
      literature].
AB  - Three cases of symptomatic umbilical residues revealed by hematuria and/or
      mictional disorders are reported. Ultrasonography, computed tomography and
      magnetic resonance imaging visualized an aspecific formation of the bladder dome.
      Total exeresis requiring partial cystectomy in all cases was curative (tow years
      follow-up). All clinical signs have disappeared.

PMID- 9765787
TI  - [Nephrectomy for cancer in pregnant women. Apropos of a case].
AB  - We report on the case of a young pregnant woman who had a malignant tumor of the
      kidney. The pregnancy did not change the gold standard therapy: radical
      nephrectomy. Because of the pregnancy the preoperative staging consisted of an
      abdominal ultrasound and a magnetic resonance imaging for the local extension,
      and of a chest X-ray looking for pulmonary metastases. According to the
      literature pregnancy, a situation of immune depression, does not increase the
      prevalence of malignant neoplasms.

PMID- 9765788
TI  - [Treatment of hemangioma of the glans penis using Nd:Yag laser. Apropos of a
      case].
AB  - Hemangioma of urinary tract are unusual, being about 2% of all hemangiomas. We
      present a case of a glans penis hemangioma. There is controversy concerning their
      treatment and outcome. Our patient was treated with a Neodymium: Yag laser
      irradiation, with complete morphological recuperation.

PMID- 9765789
TI  - [Drug-resistant genito-urinary rhabdomyosarcoma in children with primary psoas
      abscess. Apropos of a case].
AB  - We report an unusually uncommon case of genitourinary rhabdomyosarcoma in a child
      which was chemoresistant and complicated by a primary psoas abscess which
      presented as a pelvic mass associated with an abscess of the right iliac fossa.
      Ultrasound and CT investigations suggested the diagnosis of a centropelvic tumor
      which was confirmed at puncture-aspiration. MRI was most contributive giving a
      precise description of the local extension. Intensive multi-drug chemotherapy
      would appear to have improved outcome in patients with poor-prognosis Maurer
      group III tumors. In exceptional cases when no tumor response is obtained,
      carcinological surgery with large dissection, possibly with adjuvant
      radiotherapy, is indicated. Percutaneous drainage of the deep psoas abscess is as
      effective as classical surgery and spares the abdominal wall, particularly
      important if a second operation should be needed. Multidisciplinary management is
      required for the treatment of this highly malignant tumor.

PMID- 9765790
TI  - Carnosine: its properties, functions and potential therapeutic applications.
AB  - Carnosine and related dipeptides such as anserine are naturally-occurring
      histidine-containing compounds. They are found in several tissues most notably in
      muscle where they represent an appreciable fraction of the total water-soluble
      nitrogen-containing compounds. The biological role of these dipeptides are
      conjectural but they are believed to act as cytosolic buffering agents. Numerous
      studies have demonstrated, both at the tissue and organelle level, that they
      possess strong and specific antioxidant properties. Carnosine and related
      dipeptides have been shown to prevent peroxidation of model membrane systems
      leading to the suggestion that they represent water-soluble counterparts to lipid
      soluble antioxidants such as alpha-tocopherol in protecting cell membranes from
      oxidative damage. Other roles ascribed to these dipeptides include actions as
      neurotransmitters, modulation of enzymic activities and chelation of heavy
      metals. Many claims have been made in respect of therapeutic actions of carnosine
      and histidine-containing dipeptides. These include antihypertensive effects,
      actions as immunomodulating agents, wound healing and antineoplastic effects.
      Many of these claims have not been convincingly documented nor subject to
      rigorous clinical evaluation. Nevertheless, there are examples where studies have
      shown considerable promise. One is the treatment of senile cataract in dogs and
      another is in acceleration of healing of surface wounds and burns to the skin. It
      is clear from this review that many of the effects of these histidine-containing
      dipeptides, especially in regard to claims for their therapeutic effects, need to
      be subjected to critical experimental and clinical examination. Several
      applications do, however, show clear evidence of being useful therapeutic agents.

PMID- 9765791
TI  - In vivo mutational analysis of bacteriophage Mu operators.
AB  - In bacteria lysogenic for bacteriophage Mu, the phage repressor binds to a
      tripartite operator region, O1,O2,O3, to repress the lytic promoter pE, located
      in O2, and negatively autoregulate its own synthesis at the pCM promoter located
      in O3. We isolated and characterized operator mutations which lead to
      derepression of pE. Their location in the first and third repressor-consensus
      binding sequences in O2 confirms the importance of these sites for
      repressor/operator interactions.

PMID- 9765792
TI  - Long-term in vitro cultivation of Borrelia burgdorferi sensu lato strains:
      influence on plasmid patterns, genome stability and expression of proteins.
AB  - Low (7th) and high (298th/304th) in vitro passages (cultivated over a period of 3
      years) of two human Borrelia burgdorferi sensu lato strains, PKo (B. afzelii) and
      PBi (B. garinii) were compared by pulse-field gel electrophoresis, Southern blot,
      sequencing of the ospA gene, SDS-PAGE and Western blot. Digestion of genomic DNA
      with ApaI, BssHII, KspI, MluI, SmaI and XhoI did not reveal any differences
      between low and high passages. The loss of two linear plasmids with sizes of 6
      and 31 kbp was detected in strain PKo between passages 34-50 and 101-304,
      respectively, whereas the ospA-carrying plasmid remained unchanged. In contrast,
      analysis of linear plasmid profiles obtained from low and high passages of B.
      garinii strain PBi showed no differences. Sequence analysis of the ospA gene
      demonstrated no difference in the strain PBi and one nucleotide exchange in the
      strain PKo when low and high passages were compared. The observed transition (G
      A) in the third codon position did not alter the amino acid sequence. However,
      the rate of expression of the outer surface proteins OspA, OspB and OspC of
      strain PKo during low and high stages of cultivation varied significantly. In
      summary, our data suggest that the B. burgdorferi sensu lato genome is stable
      during long-term in vitro cultivation.

PMID- 9765793
TI  - The adc locus, which affects competence for genetic transformation in
      Streptococcus pneumoniae, encodes an ABC transporter with a putative lipoprotein
      homologous to a family of streptococcal adhesins.
AB  - To identify new components involved in the phenomenon of transformation in
      Streptococcus pneumoniae, a library of potential mutants has been generated by
      random insertion of an erythromycin resistance gene. Transformation-deficient
      mutants were screened using an in situ colony transformation test. The adc locus,
      which was identified in this search, was cloned and sequenced. Sequence analysis
      revealed a putative operon of three ORFs (adcC, adcB and adcA) with homology to
      ATP-binding cassette (ABC) transport operons encoding streptococcal adhesins such
      as ScaA of S. gordonii and FimA of S. parasanguis. adcA can encode a lipoprotein
      of 313 amino acid residues containing a putative metal-binding site. The
      polypeptide shows about 30% sequence identity with ScaA and FimA. We discuss
      evidence which leads us to propose that AdcA, together with a set of 14 proteins
      including ScaA, FimA and homologous adhesins, defines a new family of external
      solute-binding proteins, cluster 9, specific for metals.

PMID- 9765795
TI  - Response of Brucella suis 1330 and B. canis RM6/66 to growth at acid pH and
      induction of an adaptive acid tolerance response.
AB  - Acid pH is an environmental stress often encountered by Brucella during both the
      "environmental" and the "pathogenic" stages of its life. We have investigated the
      behaviour of B. suis biovar 1 and B. canis in acid conditions. Growth at
      suboptimal pH was characterized by a dramatic reduction in growth yield due to an
      early onset of stationary phase. B. suis was more resistant to low pH than B.
      canis, which lysed at pH 4.6. Viable counts measured after a 4-h acid shock at pH
      3.2 showed that the relative survival of B. suis was 1,000-fold greater than that
      of B. canis. An adaptive acid tolerance response (ATR) was induced in both
      species by culture at pH 5.8; however, while the acid-sensitive B. canis had more
      than a 2,000-fold increase in survival following acid shock at pH 3.2, the
      increase in survival of B. suis was only around 50-fold. The kinetics of the
      induction of ATR were followed: for B. suis, 1-2 h (1 generation) at pH 5.8 were
      required to induce acid tolerance (50-fold protection), and these levels remained
      constant over 24 h. B. canis became relatively acid-resistant after only 30-min
      exposure to pH 5.8. Levels of acid tolerance continued to increase and were
      maximal at 24 h. Stationary phase pH 7.2 cultures of either species did not
      exhibit acid resistance, suggesting that, like Salmonella, Brucella does not have
      an rpoS-controlled stationary phase acid resistance.

PMID- 9765794
TI  - Molecular characterization of a 17-kDa outer-membrane protein from Klebsiella
      pneumoniae.
AB  - A cosmid-based genomic library of Klebsiella pneumoniae 52145 (O1:K2) was
      introduced into Escherichia coli, and clones were screened for the bacteriocin
      28b resistance phenotype. One clone was found which conferred partial resistance
      to bacteriocin 28b. By using Tn5tac1 insertions, it was shown that this phenotype
      was due to the expression, in E. coli, of an outer-membrane protein (OMP) with an
      apparent molecular mass of 17 kDa (OmpK17). The DNA region defined by insertion
      mutagenesis was sequenced and found to contain an ORF of 510 bp. The deduced
      amino acid sequence has 170 residues with a theoretical molecular mass of 18.4
      kDa. The protein contains an N-terminal signal sequence of 24 amino acid
      residues. When compared with other enterobacterial OMPs, OmpK17 most closely
      resembles members of a family of small OMPs of Enterobacteriaceae the known
      functions of which appear to be related to virulence. Immunoblotting experiments
      showed that OmpK17 is also present in various K. pneumoniae strains belonging to
      different O and K serotypes.

PMID- 9765796
TI  - Isolation of a soil psychrotrophic toluene-degrading Pseudomonas strain:
      influence of temperature on the growth characteristics on different substrates.
AB  - Two psychrotrophic toluene-degrading Pseudomonas putida strains were isolated at
      low temperature from a toluene-polluted soil, thereby demonstrating that toluene
      degradation at low temperature occurred in nature, a finding of possible interest
      for soil bioremediation procedures. In one of these strains, two aromatic
      compounds (toluene and benzoate) were degraded, most likely through different
      pathways. To study the effect of the growth temperature on the metabolism of
      these substrates, we studied the evolution of the maximal growth rates with
      respect to both temperature and substrate. It was shown that not only cardinal
      temperatures but also temperature characteristics deduced from the Arrhenius plot
      of maximal growth rates differed when the different substrates were used as sole
      carbon and energy source.

PMID- 9765797
TI  - Effect of natural amphipathic peptides on viability, membrane potential, cell
      shape and motility of mollicutes.
AB  - The antibiotic activity of ten amphipathic peptides was investigated in six
      species of mollicutes belonging to the genera Acholeplasma, Mycoplasma and
      Spiroplasma. A. laidlawii was the most sensitive and M. mycoides subsp. mycoides
      SC the most resistant. Animal defence peptides (cecropins A and P1, and magainin
      2) proved to be less potent than bee-venom mellitin and most of the peptides
      produced by bacteria (globomycin, gramicidin S, surfactin and valinomycin) or
      fungi (alamethicin). Gramicidin S was by far the most active peptide, with
      minimal inhibitory concentrations ranging from 2 to 50 nM. Alamethicin,
      gramicidin S, mellitin and surfactin had a cidal effect, whilst cecropins,
      globomycin, magainin 2, polymyxin B and valinomycin proved to be static. The
      peptides altered the membrane potential of spiroplasma cells with a potency
      independent of their linear or cyclic structure. However, globomycin depolarized
      the plasma membrane only weakly, whilst polymyxin B, in order to be active,
      required prior hyperpolarization of the membrane. The peptides also induced the
      loss of cell motility and helicity in spiroplasmas, suggesting that motility and
      cell shape in these bacteria are coupled to the transmembrane electrochemical
      gradient. Globomycin, an inhibitor of signal-peptidase II, prevented the growth
      of spiroplasmas, M. gallisepticum, and M. genitalium, but not that of A.
      laidlawii and M. mycoides subsp. mycoides SC, although the latter also
      synthesized membrane lipoproteins. Inhibition of spiralin processing by
      globomycin was demonstrated in S. citri and S. melliferum, with a more pronounced
      effect in the second species.

PMID- 9765798
TI  - Detection of the Escherichia coli attaching and effacing gene (eaeA) in
      enteropathogenic strains by polymerase chain reaction.

PMID- 9765799
TI  - A cheA cheW operon in Borrelia burgdorferi, the agent of Lyme disease.
AB  - Borrelia burgdorferi sensu stricto homologues of cheA and cheW were cloned and
      characterized. A combination of strategies such as polymerase chain reaction
      (PCR) using degenerate primers, random-primed gene walking PCR and construction
      of a lamda library were used to identify the putative cheA gene. Sequence
      analysis of the DNA fragments obtained from the CT strain identified a 2,592-bp
      open reading frame (ORF) encoding an 864-amino-acid protein with significant
      similarity (53-64.6% identical residues) to the CheA of several genera of
      eubacteria. In particular, hallmarks of a histidine kinase family were found such
      as the location of the histidine autophosphorylation domain very close to the NH2
      terminus and the nucleotide-binding site. A second ORF located immediately
      downstream from the putative borrelial cheA gene encoded a 195-amino-acid protein
      which displayed a high level of similarity to bacterial CheW. Using reverse
      transcription PCR, we demonstrated that cheA and cheW form an operon with an
      upstream, unidentified ORF. The cheA and cheW homologues were located at 722-737
      kbp, 738-768 kbp and 743-824 kbp on the linear chromosomes of B. burgdorferi
      sensu stricto, B. garinii and B. afzelii, respectively. Identification of cheA
      and cheW is the first step toward elucidation of a possible role of chemotaxis in
      virulence of the Lyme disease borreliae.

PMID- 9765800
TI  - The partial sequence of the Plasmodium falciparum histone H4 gene.

PMID- 9765801
TI  - Identification of different daughter and parent subpopulations in an
      asynchronously growing Saccharomyces cerevisiae population.
AB  - Under all growth conditions, a growing Saccharomyces cerevisiae yeast population
      is extremely heterogeneous, since individual cells differ in their cell size;
      this is due to their position in the cell division cycle and their genealogical
      age. To gain insight into the structure of a growing yeast population, we used a
      recently developed flow cytometric approach which enables, in asynchronously
      growing S. cerevisiae populations, tagging of both the cell age and the protein
      content of individual cells. This approach enabled the identification of daughter
      cells belonging to different cell cycle positions (i.e. newborn, G1, S + G2 + M +
      G1*, and dividing), thus yielding information about the relative fraction in the
      whole population, cell size and variability. More limited information could be
      obtained for the parent subpopulation; however, we were able to identify and
      characterize the dividing parent cells. The coefficient of variation (CV) of the
      protein content distribution for the dividing parents (27) was much higher than
      the CV of dividing daughters (18). Further findings obtained indicated a large
      overlap between the cell protein content distributions of daughter and parent
      cells as well as between the protein content of cells of the same subpopulation
      but belonging to different stages of the cell division cycle. The analysis of
      these differences enables a better understanding of the complex structure of an
      asynchronously growing yeast population.

PMID- 9765802
TI  - Cloning and expression of colonization factor antigen I (CFA/I) epitopes of
      enterotoxigenic Escherichia coli (ETEC) in Salmonella flagellin.
AB  - Oligonucleotides coding for linear epitopes of the fimbrial colonization factor
      antigen I (CFA/I) of enterotoxigenic Escherichia coli (ETEC) were cloned and
      expressed in a deleted form of the Salmonella muenchen flagellin fliC (H1-d)
      gene. Four synthetic oligonucleotide pairs coding for regions corresponding to
      amino acids 1 to 15 (region I), amino acids 11 to 25 (region II), amino acids 32
      to 45 (region III) and amino acids 88 to 102 (region IV) were synthesized and
      cloned in the Salmonella flagellin-coding gene. All four hybrid flagellins were
      exported to the bacterial surface where they produced flagella, but only three
      constructs were fully motile. Sera recovered from mice immunized with
      intraperitoneal injections of purified flagella containing region II (FlaII) or
      region IV (FlaIV) showed high titres against dissociated solid-phase-bound CFA/I
      subunits. Hybrid flagellins containing region I (FlaI) or region III (FlaIII)
      elicited a weak immune response as measured in enzyme-linked immunosorbent assay
      (ELISA) with dissociated CFA/I subunits. None of the sera prepared with purified
      hybrid flagella were able to agglutinate or inhibit haemagglutination promoted by
      CFA/I-positive strains. Moreover, inhibition ELISA tests indicated that antisera
      directed against region I, II, III or IV cloned in flagellin were not able to
      recognize surface-exposed regions on the intact CFA/I fimbriae.

PMID- 9765803
TI  - Genome size variation among recent human isolates of Salmonella typhi.
AB  - We performed genome size estimation of 17 recent human isolates of Salmonella
      typhi from geographically diverse regions using pulsed-field gel electrophoresis
      (PFGE) after digestion of chromosomal DNA with restriction endonucleases XbaI (5'
      TCTAGA-3'), AvrII (5'-CCTAGG-3') and SpeI (5'-ACTAGT-3'), and summation of the
      sizes of restriction fragments obtained. All 17 isolates had circular
      chromosomes, and genome sizes differed by as much as 959 kb, ranging from 3,964
      to 4,923 kb (mean genome size = 4,528 kb). The data obtained confirm the
      usefulness of PFGE in studies of bacterial genome size and are in agreement with
      recent results indicating considerable genetic diversity and genomic plasticity
      of S. typhi. The variation in genome sizes noted may be relevant to the observed
      biological properties of this important human pathogen, including its virulence.

PMID- 9765804
TI  - Molecular characterization of an n-alkane-degrading bacterial community and
      identification of a new species, Acinetobacter venetianus.
AB  - Twenty-five bacterial strains isolated from the Venice lagoon and implicated in
      the degradation of n-alkanes, n-alkanols, n-alkanals and n-alkanoates were
      characterized in molecular and physiological terms. The isolates were grouped by
      amplified ribosomal DNA restriction analysis (ARDRA) into seven clusters,
      corresponding to seven species, six of which were identified on the basis of 16S
      rDNA sequencing. Genetic variability among strains was shown by random amplified
      polymorphic DNA (RAPD). Only strains of the new species Acinetobacter venetianus
      grew with n-alkanes (C10, C14 and C20) and their respective oxidation products as
      sole carbon sources. Strains of the other three species identified thrived on n
      alkane oxidation products (n-alkanols, n-alkanals, n-alkanoates). The other three
      species were not able to grow on any of the substrates tested. Analysis of
      plasmid content showed that only A. venetianus strains harboured plasmids. These
      plasmids contained sequences homologous to the Pseudomonas oleovorans alkBFGH
      genes.

PMID- 9765805
TI  - Emergence of Cu(++)-tolerant mutants defective in gellan synthesis in Cu(++)
      stressed cultures of Sphingomonas paucimobilis.
AB  - Cells defective in gellan synthesis appeared during cultivation of the gellan gum
      producing strain Sphingomonas paucimobilis R40 with inhibitory concentrations of
      copper, supplied as CuCl2. The percentage of less mucoid colonial variants
      dramatically increased with the increase in Cu++ supplementation, reaching 85% of
      total viable cells at the maximal concentration for growth. Results reported in
      this work indicate that emergence of colonial variants defective in gellan
      synthesis results from Cu(++)-induced mutation and the growth advantage of these
      mutants in Cu(++)-stressed cultures. In fact, DNA homologous recombination
      strongly increased with the increase in copper supplementation as indicated by
      the regeneration of kanamycin-resistant cells of R40 harbouring plasmid pBX404-7,
      which carries two non-overlapping truncated genes derived from a gene conferring
      kanamycin resistance. The four major groups of colonial mutants that emerged from
      Cu(++)-stressed cultures of R40 exhibited reduced growth rate and biomass yield
      in the absence of Cu++ stress and produced decreased levels of exopolysac-charide
      (EPS) which yielded solutions of lower or negligible viscosity. The level of
      increased Cu++ tolerance of these mutants, assessed by the inhibitory effect of
      Cu++ on growth, correlated with the degree of loss of the ability to secrete high
      molecular-mass EPS. Consistent with the growth advantage of gellan-defective
      mutants in Cu(++)-stressed cultures, the non-producing strain RP10, spontaneously
      obtained during extended cultivation of R40, also exhibited a higher tolerance to
      Cu++. In addition, its non-mucoid phenotype was stably maintained during Cu(++)
      stressed cultivation despite the stimulation of homologous recombination by Cu++.

PMID- 9765806
TI  - Glycoside hydrolase production by an anaerobic rumen fungus Caecomyces communis.
AB  - The ruminal fungus Caecomyces communis was grown anaerobically either in a
      discontinuous cultivation system or in a fermentor with daily withdrawal and
      addition of fresh medium. Lowe and Orpin media were tested. The best culture
      conditions for glycoside hydrolase production were obtained in Lowe medium with
      daily fresh medium addition, whereas the Orpin medium with ruminal fluid was
      favourable to fungal growth and to the enzyme export process. Among glycoside
      hydrolases assessed in both culture fluid and cellular homogenate, beta-D
      fucosidase activity was preponderant. Most studied enzymes were mainly associated
      with cells (from 50% to 99%). Glycoside hydrolase activities were constitutive,
      but their level was regulated by a carbon source. beta-D-fucosidase and beta-D
      xylosidase activity production was activated by the association of glucose plus
      cellobiose, whereas beta-D-glucosidase activity production was stimulated by
      cellobiose alone. Enzyme release could be favoured by glucose alone or by Ray
      grass hay added to glucose plus cellobiose.

PMID- 9765807
TI  - Increase in beta-galactosidase activity in a non-isothermal bioreactor utilizing
      immobilized cells of Kluyveromyces fragilis: fundamentals and applications.
AB  - The beta-galactosidase activity of Kluyveromyces fragilis cells immobilized in a
      kappa carrageenan gel was studied in a bioreactor functioning under isothermal
      and non-isothermal conditions. We observed an increase in enzyme activity which
      was found to be proportional to the intensity of the temperature gradient applied
      across the biocatalytic membrane, as well as to the average temperature of the
      bioreactor. The efficiency of such a non-isothermal bioreactor was calculated
      with respect to the yield of a bioreactor working under comparable isothermal
      conditions and was evaluated in terms of reduction of processing times in
      industrial applications. The possibility that enzyme activity in living cells is
      affected by non-isothermal conditions naturally existing owing to metabolic heat
      production is also discussed.

PMID- 9765808
TI  - RegF, an SspA homologue, regulates the expression of the Neisseria gonorrhoeae
      pilE gene.
AB  - The Neisseria gonorrhoeae pilE gene codes for a type IV pilin, the major subunit
      of pili which constitute an essential virulence factor during gonococcal
      infection. Expression of pilE seems to be highly regulated, which may allow
      piliation to adapt to growth conditions. From an N. gonorrhoeae genomic library,
      we selected plasmid pNG200 encoding a protein (RegF) which caused a 5-fold
      increase in the expression of pilE::cat fusion in Escherichia coli. This
      regulation was mediated via the complex pilE promoter region, comprising
      potential sigma 70- and sigma 54-dependent promoters, and could not be observed
      in the absence of an active sigma 54 factor. The RegF protein (23,149 Da) showed
      42% identity with the E. coli "stringent starvation protein", SspA. This protein
      was shown to interact with the RNA polymerase holoenzyme and to play a role in
      the expression of at least 11 proteins in E. coli. In an N. gonorrhoeae strain
      carrying a regF::mTn3Cm3 mutation constructed by allelic exchange, it was
      observed that pilin expression was enhanced. Our results were consistent with a
      model in which (i) in N. gonorrhoeae, RegF acts as a negative regulator of pilE
      transcription, and (ii) in E. coli, RegF increases pilE transcription by
      preventing sigma 54-associated steric hindrance at pilE promoters described
      previously.

PMID- 9765809
TI  - Effect of saline concentration, pH and growth temperature on the invasive
      capacity of Listeria monocytogenes.
AB  - The invasive ability of Listeria monocytogenes was monitored after treatment at
      different pH, temperature and salt concentrations. We found a complete loss of
      invasive ability in bacteria grown at pH < or = 4.5 independently of the
      incubation temperature (4, 22 and 30 degrees C). Increasing salt concentrations
      at 22 and 30 degrees C had no effect at pH 7, while drastically affecting
      invasive ability at pH 5. The expression of two proteins of 30 and 88 kDa,
      extracted from the culture supernatant and the cell wall, respectively, was
      detected only in cells grown under normal conditions, but not after low pH and
      high salt concentration treatment.

PMID- 9765810
TI  - Strategy for the detection of Helicobacter species by amplification of 16S rRNA
      genes and identification of H. felis in a human gastric biopsy.
AB  - The aim of the present work was to develop polymerase chain reactions (PCRs)
      based on the conserved nucleotide sequence of the 16S rRNA gene for detection of
      bacteria of the Helicobacter genus in human antral biopsy samples. The assay for
      Helicobacter spp was developed by amplifying a 399-bp 16S rRNA gene sequence
      specific to the genus Helicobacter. The identity of the amplicon was confirmed by
      hybridization with an internal probe and by restriction by endonuclease VspI
      showing two expected fragments of 295 and 104 base pairs. A total of 65 dyspeptic
      patients from France and New Caledonia were screened for Helicobacter spp
      infection through the use of the following diagnostic assays on biopsy specimens
      collected through endoscopy: direct detection of bacteria in histological
      sections by Giemsa and Warthin Starry staining, urease test and bacterial
      isolation, PCR for Helicobacter pylori ureC/glmM gene, and PCR targeted to 16S
      rRNA genes. The 16S rRNA gene PCR assay was able to detect down to 680 bacterial
      cells, as assessed by agarose gel electrophoresis, and down to 4 bacterial cells
      by hybridization of amplicon with the internal probe. The 16S rRNA PCR test was
      100% specific and sensitive; results obtained with this test were in agreement
      with the visualization of bacteria by histology. Urease test and culture were
      86.4% and 22.7% sensitive, and 96.5 and 100% specific, respectively. The H.
      pylori ureC/glmM gene-based PCR was 100% specific and only 95.4% sensitive, since
      one biopsy from a Melanesian patient contained a Helicobacter strain other than
      H. pylori. For this Melanesian patient, a branch-specific PCR targeting the
      epsilon branch of Proteobacteria was used to amplify a 967-bp amplicon. This
      amplicon was sequenced and matched with the H. felis sequence. This was confirmed
      using an H. felis-specific urease PCR test.

PMID- 9765811
TI  - Characterization of avian Chlamydia psittaci strains using omp1 restriction
      mapping and serovar-specific monoclonal antibodies.
AB  - In the present study, 60 avian Chlamydia psittaci isolates were characterized
      using restriction fragment length polymorphism as well as serovar-specific
      monoclonal antibodies, enabling a comparison between the two characterization
      methods. Sixty avian C. psittaci isolates were characterized by Alul restriction
      mapping of the major outer membrane protein gene omp1 obtained after
      amplification by the polymerase chain reaction. The 60 avian C. psittaci strains
      were also characterized using serovar-specific monoclonal antibodies in a
      microimmunofluorescence test. Digestion of 60 avian C. psittaci omp1 amplicons by
      Alul generated 5 of the 6 known distinct restriction patterns (A, B, D, E and F).
      Restriction pattern C was not observed. Serotyping revealed 4 avian C. psittaci
      serovars (A, B, C and D). None of the 60 isolates was typed as serovar E. AluI
      restriction patterns A, B, D and E corresponded in 98% of the cases to serovars
      A, B, C and D, respectively. One isolate, classified as serovar A, generated
      restriction pattern F instead of A. Genotyping enabled a more precise
      differentiation of avian C. psittaci serovar A strains. Serovar A strains were
      divided into two groups according to their Alul restriction pattern (A or F). For
      epidemiological studies, genotyping can thus be a highly valuable alternative to
      serotyping, especially when applied directly to the clinical samples.

PMID- 9765812
TI  - Overexpression, purification and characterization of Dictyostelium calcineurin A.
AB  - The catalytic subunit of Ca2+/calmodulin-dependent protein phosphatase
      (calcineurin A) was overexpressed about 50-fold in Dictyostelium discoideum cells
      transformed with a vector containing the cDNA for D. discoideum calcineurin A
      under control of the actin-6 promoter. In crude lysates from the overexpressing
      cell line, high Ca2+/calmodulin-stimulated phosphatase activity was detected.
      Calcineurin A was purified by anion exchange chromatography and calmodulin
      Sepharose affinity chromatography, and the enzymatic activity of the isolated
      protein was characterized. Its phosphatase activity was strictly dependent on the
      addition of divalent metal ions such as Mg2+ or Mn2+. Disulphide-reducing agents
      increased the activity more than 10-fold. Ca2+/calmodulin stimulated the activity
      by a factor of 2.5-5. Despite the high extra Ca2+/calmodulin-dependent
      phosphatase activity, the overexpressing cell line showed no phenotypic
      aberrations.

PMID- 9765813
TI  - Prochlorothrix hollandica PCC 9006: genomic properties of an axenic
      representative of the chlorophyll a/b-containing oxyphotobacteria.
AB  - Prochlorothrix hollandica is an oxygenic photosynthetic prokaryote that differs
      from the cyanobacteria in having chlorophyll a/b-protein complexes instead of
      phycobilisomes as major light-harvesting antennae. We report the isolation and
      culturing of an axenic strain of P. hollandica, available from the Pasteur
      Culture Collection of Cyanobacteria as strain PCC 9006. The strain has a mean DNA
      base composition of 51.6 +/- 0.1 mol% G+C and a genomic complexity of 3.37 +/-
      0.17 x 10(9) daltons (5,505 kb). A reiterated DNA sequence represents
      approximately 4.4% of the genome. Restriction enzyme isoschizomers with different
      sensitivities to base methylation were used to demonstrate that most A residues
      in the sequence GATC are methylated in P. hollandica DNA and that this
      methylation increases with culture age. Furthermore, some C residues are
      methylated, although the specificity of the C methylation system does not match
      that of well-characterized C methylases. Nucleotide analysis showed that up to
      approximately 3.5% of both dA and dC residues are methylated in P. hollandica
      DNA.

PMID- 9765814
TI  - Production of substituted naphthalene dihydrodiols by engineered Escherichia coli
      containing the cloned naphthalene 1,2-dioxygenase gene from Pseudomonas
      fluorescens N3.
AB  - Naphthalene dioxygenase, a key enzyme in the dihydroxylation of naphthalene, is
      encoded by the plasmid pN3, responsible for naphthalene metabolism in Pseudomonas
      fluorescens N3. The naphthalene dioxygenase, including all the sequences for its
      expression and the regulatory region, has been localized on the 4.3-kb HindIII
      ClaI fragment and on the 3.5-kb HindIII fragment of the plasmid pN3, by Southern
      analysis using as probes nahA and nahR genes, the homologous genes of the plasmid
      NAH7 from Pseudomonas putida G7. We cloned in Escherichia coli JM109 the
      dioxygenase gene and its regulatory region and developed an efficient bacterial
      system inducible by salicylic acid, able to produce dihydrodiols. E. coli
      containing recombinant plasmids carrying the dioxygenase gene were analysed for
      their potential as a biocatalytic tool to produce dihydrodiols from different
      naphthalenes with the substituent on the aromatic ring at the alpha or beta
      position. The dihydrodiols, identified by HPLC (high-performance liquid
      chromatography) and 1H-NMR (nuclear magnetic resonance) were produced with yields
      ranging from 50 to 94%. The degree of bioconversion efficiency depends on the
      nature and the position of the substituent and indicates the broad substrate
      specificity of this dioxygenase and its potential for the production of a wide
      variety of fine chemicals.

PMID- 9765815
TI  - Biodegradation of phenols by a eukaryotic alga.

PMID- 9765816
TI  - Further genetic analysis of the C-terminal external loop region in Escherichia
      coli maltoporin.
AB  - LamB specifically facilitates the diffusion of maltose and maltodextrins through
      the bacterial outer membrane, and acts as a general (i.e. non-specific) porin for
      small hydrophilic molecules (< 600 daltons). We reported previously that deletion
      of the last predicted external domain near the C-terminus of the Eschirichia coli
      LamB protein (residues 376 to 405), affected in vivo the binding and transport of
      maltodextrins (specific pore functions), and also increased bacterial sensitivity
      to large antibiotics. The residues covered by this deletion correspond almost
      exactly to the major cell surface loop of LamB on the structural model based on X
      ray crystallography (loop L9, residues 375 to 405). The L9 loop comprises a large
      central portion, which varies in size and sequence between the LamB proteins from
      different species. This variable region is flanked by two highly charged and
      conserved portions, which overlap with the adjacent beta strands. To identify
      subregions in L9 that influence the pore properties of LamB, we constructed and
      analysed nine mutants in loop L9 and its flanking sequences. Deletion of the 23
      amino-acids central variable portion of the loop (residues 379 to 401), and
      deletion of the downstream conserved region (residues 402 to 409), only
      moderately affected specific maltoporin function. In contrast, deletion of the
      conserved region (residues 372 to 378) upstream of the variable portion strongly
      decreased specific maltoporin function and also increased sensitivity to large
      antibiotics, accounting for most, if not all, of the effects of the complete
      deletion of L9.

PMID- 9765817
TI  - Activity of protein MalE (maltose-binding protein) fused to cytoplasmic and
      periplasmic regions of an Escherichia coli inner membrane protein.
AB  - We analysed the properties of mature MBP (maltose-binding protein or MalE
      protein) fused to an integral cytoplasmic membrane protein of Escherichia coli.
      Fusion of MalE to the first MalG periplasmic loop enabled a strain defective in
      the malE gene to utilize maltose. In contrast, fusion of MalE to a cytoplasmic
      loop did not complement the malE delta 444 deletion. We obtained results highly
      correlated with those obtained by using alkaline phosphatase as a reporter for
      the topology of MalG. We discuss the possibility of genetically determining the
      topology of cytoplasmic membrane proteins by a method based on engineered fusions
      to MBP.

PMID- 9765818
TI  - The recA gene from Streptomyces rimosus R6: sequence and expression in
      Escherichia coli.
AB  - The recA gene from Streptomyces rimusus encodes a 376-amino acids polypeptide
      (M(r) 39,702) that is one of the largest bacterial RecA proteins observed.
      Detailed analyses of the Streptomyces RecA proteins showed that all possess an
      additional and unique C-terminal, rich in lysines and alanines, which can form an
      additional terminal alpha helix. Expression of the S. rimosus RecA protein in
      Escherichia coli FR333 (delta recA306) was demonstrated using antibodies raised
      against E. coli RecA protein; expression was possible only from the S. rimosus
      promoter. A Streptomyces-E. coli-like promoter sequence (TTGACA-18bp-TCTTAT) was
      found in the A+ T-rich region 135-165 base pairs upstream from the initiation
      codon and was related to Bacillus subtilis DNA damage-inducible promoters.

PMID- 9765819
TI  - Distribution of surface-exposed antigenic glycolipids in recent clinical isolates
      of Mycobacterium tuberculosis.
AB  - The distribution of surface-exposed antigenic glycolipids in seven recent
      clinical isolates of Mycobacterium tuberculosis was established. Thin-layer and
      liquid chromatographies revealed a uniformity in the glycolipid pattern. Chemical
      analysis of the individual glycolipids of a selected strain enabled the
      identification of glycolipids of serological interest in all the other clinical
      isolates. Phenolic glycolipid-Tb1 (PGL-Tb1) was lacking in all strains, but
      appreciable amounts of a partially deglycosylated version (PGL-Tb1D) were present
      in the seven isolates. Diacyltrehaloses (DATs) were detected in all strains,
      showing themselves to be major glycolipids. Lipooligosaccharides (LOS-II) were
      present in the seven strains studied though only in trace amounts. These results
      shed new light on the open debate on the distribution of these interesting
      glycolipids in typical clinical isolates of M. tuberculosis. In the search for a
      serological test for tuberculosis, and in accordance with our observations, we
      believe that PGL-Tb1 and LOS-II should not be the target molecules for serology
      and that it is worthwhile to continue investigating the value of DATs as
      antigens. We also believe that it would be of interest to undertake research to
      assess the usefulness of PGL-Tb1D as an antigen.

PMID- 9765820
TI  - Lipopolysaccharide biosynthesis genes in koala type I Chlamydia: cloning and
      characterization.
AB  - We showed in 1988 that there are two strains of Chlamydia psittaci which infect
      the koala (Phascolarctos cinereus). In order to further investigate the role of
      these chlamydial strains in pathogenesis, we have attempted to identify genes of
      koala type I strain chlamydia which are involved in the immunogenic response.
      Transformation of Escherichia coli with a plasmid containing a 6.3-kb fragment
      (pKOC-10) of C. psittaci DNA caused the appearance of a specific chlamydial
      lipopolysaccharide (LPS) epitope on the host strain. The smallest DNA fragment
      capable of inducing the expression of chlamydial LPS was an XbaI fragment, 2.4 kb
      in size (pKOC-5). DNA sequence analysis of the complete fragment revealed regions
      of high identity, at the amino acid level, to the gseA genes of C. pneumoniae, C.
      psittaci 6BC and C. trachomatis, and the kdtA gene of E. coli which code for
      transferases catalysing the addition of 3-deoxy-D-manno-octulosonic acid (Kdo)
      residues to lipid A. Two open reading frames (ORFs) of 1,314 and 501 nucleotides
      in size, within the 2.4-kb fragment, were evident, and mRNA species corresponding
      to these ORFs were detected by Northern analysis. Both ORF1 and ORF2 are required
      for the appearance of chlamydia-specific LPS on the surface of recombinant E.
      coli.

PMID- 9765822
TI  - Heterogeneity of Lyme disease spirochaetes within individual vector ticks.
AB  - To determine whether Lyme disease spirochaetes (Borrelia burgdorferi) within
      vector ticks (lxodes dammini) sampled from enzootic sites comprise single or
      mixed populations, we compared their reactivity to a polyclonal rabbit immune
      serum with that to a battery of monoclonal antibodies (mAb) against OspA, OspB
      and flagellin. More spirochaetes were recognized by the polyclonal antibody than
      with the mAbs. Spirochaetes from field-sampled ticks reacted poorly to mAbs
      against OspB. No such differences in reactivity to polyclonal or monoclonal
      antibodies were observed for the N40 strain of B. burgdorferi from BSK cultures
      and infected laboratory-reared vector ticks. We conclude that in nature each tick
      may be infected by an antigenically heterogeneous mixture of spirochaetes.

PMID- 9765821
TI  - An mpb-64 flanking sequence specific for Mycobacterium bovis.
AB  - A clone carrying a plasmid with the mpb-64 gene and 3' flanking sequences
      (plasmid pMBA122) was detected during the screening of a Mycobacterium bovis
      genomic library with sera from infected cattle. When the pMBA122 insert was used
      as a probe in Southern blots against PvuII-digested mycobacterial DNA, it
      distinguished the different M. tuberculosis complex species. This probe
      hybridized with a 7-kb band in M. tuberculosis, a 5-kb band in M. bovis and a 3
      kb band in M. tuberculosis complex strains from wild seals. Smal genomic
      digestions enabled us to locate this polymorphic region downstream of the mpb-64
      gene. In order to clone this particular region, we designed a pair of PCR
      primers. Unexpectedly, these primers amplified only M. bovis DNA; no
      amplification was seen in M. tuberculosis DNA. When the annealing temperature was
      lowered from 70 to 55 degrees C, an amplification product of the same size was
      obtained with M. tuberculosis. This product was cloned and sequenced, and showed
      partial homology to the M. bovis amplified fragment. Therefore, this region
      comprises M. bovis sequences with a lower homology with M. tuberculosis than
      other compared sequences. This suggests that a more precise differentiation
      method at the species level for the M. tuberculosis complex could be achieved
      using PCR directed to this region.

PMID- 9765823
TI  - Exchange of Pseudomonas aeruginosa strains among cystic fibrosis siblings.
AB  - The molecular epidemiology of Pseudomonas aeruginosa infection in cystic fibrosis
      (CF) siblings was analysed by DNA fingerprinting using arbitrary primed
      polymerase chain reaction. A total of 306 strains collected from six pairs of
      siblings over a period of 20-126 months (median 64) was studied. Fifty-four
      different P. aeruginosa genotypes were recognized. Two out of six pairs of
      siblings were ultimately colonized by identical strains, and it was shown that a
      single P. aeruginosa clone can persist in an individual patient for over ten
      years. No overlap in P. aeruginosa genotypes was encountered between families,
      whereas in all families at least transient cross-colonization with the same
      genotype was observed. This finding demonstrates that P. aeruginosa cross
      infection or acquisition of the same strain from an identical environmental
      source exists within the family situation, but does not always result in a long
      term colonization by identical genotypes in all family members suffering from CF.

PMID- 9765824
TI  - Electrophoretic pattern of peptidoglycan hydrolases, a new tool for bacterial
      species identification: application to 10 Lactobacillus species.
AB  - Lactobacilli have been used as industrial starters for a long time, but in many
      cases their phenotypic identification is still neither easy nor reliable.
      Previously we observed that the cell wall peptidoglycan hydrolases of
      Lactobacillus helveticus were highly conserved enzymes; the aim of the present
      work was to determine whether peptidoglycan hydrolase patterns obtained by
      renaturing SDS-PAGE could be of interest in the identification of lactobacilli
      species. For that purpose, the peptidoglycan hydrolase patterns of 94 strains of
      lactobacilli belonging to 10 different species were determined; most of the
      species studied are used either in dairy, meat, bakery or vegetable
      fermentations: L. helveticus, L. acidophilus, L. delbrueckii, L. brevis, L.
      fermentum, L. jensenii, L. plantarum, L. sake, L. curvatus and L. reuteri. Within
      a species, the strains exhibited highly similar patterns: the apparent molecular
      weights of the lytic bands were identical, with only slight variations of
      intensity. Moreover, each species, including phylogenetically close species such
      as L. sake and L. curvatus, or L. acidophilus and L. helveticus, gave a different
      pattern. Interestingly, the closer the species were phylogenetically, the more
      related were their patterns. The sensitivity of the method was checked using
      various quantities of L. acidophilus cells: a peptidoglycan hydrolase extract of
      5 x 10(6) cells was sufficient to obtain an informative pattern, as was a single
      colony. Finally, the method was also successfully applied to distinguish two
      Carnobacterium species. In conclusion, the electrophoretic pattern of
      peptidoglycan hydrolases is proposed as a new tool for lactobacilli
      identification: it is rapid, sensitive and effective even for phylogenetically
      close species. Furthermore, this work provides the first evidence of the
      potential overall taxonomic value of bacterial peptidoglycan hydrolases.

PMID- 9765825
TI  - Relationship between the physiology of Enterobacter agglomerans CNCM 1210 grown
      anaerobically on glycerol and the culture conditions.
AB  - In a preliminary study, levels of activity of enzymes involved in anaerobic
      glycerol catabolism by Enterobacter agglomerans grown in batch cultures regulated
      in a pH range of 6.5-8.0 were monitored. That study showed that activities of key
      enzymes of the downstream metabolism of glycerol--glyceradehyde-3-phosphate
      dehydrogenase (GAP-DH), lactate dehydrogenase and pyruvate formate lyase--were
      strongly dependent on the culture pH. To investigate the influence of pH on the
      physiology of the strain, E. agglomerans was grown anaerobically in a continuous
      culture supplied with glycerol as the sole carbon source and regulated at pH 8. A
      complete biochemical analysis was performed and was compared with that previously
      described for the continuous culture regulated at pH 7. A limitation of the
      glycolytic flux at the level of GAP-DH was demonstrated at high dilution rate,
      resulting in an overflow metabolism through the 1,3-propanediol formation
      pathway. Increasing the specific rate of glycerol consumption also resulted in
      enhanced lactate production due to limitation by the pyruvate decarboxylation
      step. Finally, changing the culture pH significantly modified the enzymatic
      profile of E. agglomerans, and it enabled the stability of the culture to be
      increased by preventing the accumulation in the fermentation broth of 3
      hydroxypropionaldehyde, an inhibitory metabolite, when the glycerol supply was
      suddenly increased.

PMID- 9765826
TI  - A nested PCR method to detect Listeria monocytogenes in artificially contaminated
      blood specimens.
AB  - A nested PCR-based test was developed for the detection of Listeria monocytogenes
      in blood specimens from patients with listeriosis. Two pairs of oligonucleotide
      primers were designed to amplify a 1395-bp and a 453-bp fragment of the iap gene
      of L. monocytogenes. Amplified products were analysed with gel electrophoresis
      and stained with ethidium bromide. The PCR method described could be routinely
      used to diagnose listeriosis.

PMID- 9765827
TI  - Glycolipid antigen for use in diagnostic assays for bovine tuberculosis.
AB  - A glycolipid antigen, was isolated, purified and characterized from Mycobacterium
      bovis An5. Chemical analysis (thin-layer chromatography, nuclear magnetic
      resonance and infrared spectra) showed that this glycolipid was a 2,3-di-O-acyl
      trehalose (DAT), similar to the DAT of M. tuberculosis. This antigen was used to
      establish ELISA-based serodiagnostic tests for M. bovis-infected cattle. The
      sensitivity and specificity of the assay were investigated using sera of cattle
      from tuberculosis-free herds and from tuberculosis-infected herds. No correlation
      was found between DAT-ELISA and the skin test, nor between DAT-ELISA and
      interferon-gamma with bovine purified protein derivative. The antibody titres
      were not related to cell-mediated immunity. Although the antigen was highly
      specific (95.9%), the sensitivity of DAT-ELISA, as judged from assays in
      bacteriologically confirmed tuberculosis, was low (29 to 36.8%). The low
      sensitivity of ELISA might also be attributed to a reciprocal relationship
      between B-cell proliferation and T-cell protective immunity.

PMID- 9765828
TI  - Genotyping of Lactobacillus delbrueckii subsp. bulgaricus and determination of
      the number and forms of rrn operons in L. delbrueckii and its subspecies.
AB  - Three different approaches (whole-cell protein profiles, DNA fingerprinting
      combined with pulsed-field gel electrophoresis and analysis of rDNA genes) were
      used to characterize thirty-one strains of Lactobacillus delbrueckii subsp.
      bulgaricus from different dairy products, and three type strains belonging to L.
      delbrueckii subsp. delbrueckii, L. delbrueckii subsp. lactis and L. delbrueckii
      subsp. bulgaricus. Moreover, the number and different forms of rrn operons in L.
      delbrueckii and its subspecies were defined. At the strain typing level, Notl
      macrorestriction analysis permitted grouping of the 32 strains of L. delbrueckii
      subsp. bulgaricus into 23 restriction patterns, providing a high degree of
      discriminatory power. Among whole-cell protein profiles, PCR analysis of rDNA
      genes and ribotyping, the latter method seemed to be the most reliable approach
      to characterizing the subspecies belonging to L. delbrueckii. Ribotyping combined
      with enzymes such as HindIII and EcoRI showed that at least six rrn operons were
      present in L. delbrueckii and its subspecies; two forms of rrn operons were
      present in the subspecies lactis and bulgaricus and four forms were present in
      the subspecies delbrueckii.

PMID- 9765829
TI  - Metal biosorption: a structured data space?

PMID- 9765830
TI  - Recent advances in the mechanistic understanding of metal mobility and
      interaction with microbial biomass.

PMID- 9765831
TI  - Fundamentals of the application of biosorption to the separation of uranium from
      mining drainage waters.

PMID- 9765832
TI  - Engineering polysaccharides for biosorption of heavy metals at oil/water
      interfaces.

PMID- 9765834
TI  - Membrane processes in the resistance of microorganisms to heavy metals.

PMID- 9765833
TI  - Flotation process for the recovery of metals and for the biodecontamination of
      waters and soils contaminated by the Chernobyl accident.

PMID- 9765835
TI  - The use of an Alcaligenes eutrophus biofilm in a membrane bioreactor for heavy
      metal recovery.

PMID- 9765836
TI  - Bioaccumulation of heavy metals, and application to the remediation of acid mine
      drainage water containing uranium.

PMID- 9765837
TI  - Microbially-mediated reduction and removal of technetium from solution.

PMID- 9765838
TI  - Cell-based biosensors for environmental monitoring with special reference to
      heavy metal analysis.

PMID- 9765839
TI  - Bacterial metal-lux biosensors for a rapid determination of the heavy metal
      bioavailability and toxicity in solid samples.

PMID- 9765840
TI  - Alcaligenes eutrophus as a model system for bacterial interactions with heavy
      metals in the environment.

PMID- 9765841
TI  - Group A streptococcal isolate 64/14 expresses surface plasmin-binding structures
      in addition to Plr.
AB  - A recombinant plasmin receptor (Plr) gene product originally cloned from group A
      streptococcal isolate 64/14 was analysed for its ability to bind plasmin(ogen)
      and to account for all the surface plasmin-binding properties of streptococcal
      isolate 64/14. Functional analysis of recombinant Plr demonstrated that the
      protein exhibited equal reactivity with human Lys-plasmin and Lys-plasminogen,
      but significantly lower reactivity with Glu-plasminogen. Plasmin-binding was both
      inhibitable and elutable by lysine or lysine analogs, and active plasmin bound to
      recombinant Plr was not neutralized by alpha 2-antiplasmin. Thus, the plasmin
      binding properties of recombinant Plr correlated with the plasmin-binding
      phenotype of the intact streptococcal isolate 64/14. In addition, fluid-phase
      recombinant Plr could completely inhibit binding of plasmin to either immobilized
      recombinant Plr or group A streptococcal isolate 64/14 with equal efficiency,
      indicating that surface-expressed Plr could account for all the plasmin-binding
      properties of the intact organism. An IgM monoclonal antibody to recombinant Plr
      that specifically recognized a surface structure on streptococcal isolate 64/14
      significantly inhibited the binding of plasmin to the recombinant protein;
      however, the antibody was not successful at inhibiting plasmin-binding to the
      intact bacteria, indicating the presence of other plasmin-binding structures on
      the bacterial surface in addition to Plr.

PMID- 9765842
TI  - Comparative analysis of the genomic DNA terminal regions of the lactococcal
      bacteriophages from species c2.
AB  - In an attempt to compare the cos intergenic region and bordering ORFs from
      Lactococcus lactis bacteriophages of the species c2, the nucleotide sequence of a
      2479-bp fragment containing the cos site of phage P001 DNA was determined and
      compared with the corresponding regions of phages c2, bIL67 and P6 (partial
      sequence), which belong to species c2. This comparative analysis revealed that
      some characteristic features of the cos intergenic region are conserved in all
      members of species c2. Some of them are specific to species c2, as is the case
      for a GC-rich repeat in phase with the double helix that is located close to cos.
      One conserved motif seems to be more general, as it is found in all the cos
      regions of L. lactis bacteriophages that have been sequenced. It consists in a 4
      nt indirect repeat TCAN/NACT located in a 15-bp fragment containing cos. This
      motif may be related to terminase specificity, as most of the cos asymmetric
      cleavages identified up to now are located within, or at the border of, these
      indirectly repeated sequences. Finally, some of the conserved DNA motifs of the
      species c2 cos-intergenic region seem to be even more general, as they are
      homologous to the lambda-R sites known to be involved in the maturation and the
      encapsidation of phage lambda DNA. Our comparative analysis also showed that
      within c2 phage DNAs, large blocks of sequences, i.e. the intergenic cos region
      and ORF/17 on the one hand, and ORF/16 on the other hand, evolved as distinct
      entities, probably by block recombination between phage DNAs of the same species.

PMID- 9765843
TI  - Mu gem2ts DNA integration is not necessary for induction of synchrony of cell
      division in Escherichia coli K12.
AB  - The gem2ts mutant of bacteriophage Mu induced synchrony of cell division on
      bacteria surviving infection. Induction of synchronous growth could also be
      observed as a response to the entire infected bacterial population, as in the
      case of infection of hic mutants, a peculiar class of gyrB alleles. After Mu wild
      type or Mu gem2ts infection of hic mutants, there was a lack of viral DNA
      integration and replication, while phage gene expression (including that of A
      gene, coding for the transposase) seemed to be quite normal. These data indicate
      that the mechanism of bacterial synchronization induced by Mu gem2ts does not
      require integration nor replication of the phage DNA.

PMID- 9765844
TI  - Initial steps of wall protoplast regeneration in Candida albicans.
AB  - Cell wall regeneration of individual Candida albicans yeast and mycelial
      protoplasts was studied with confocal and electron microscopy using polyclonal
      antibodies and lectins. Quantitative measurements of the fluorescence emitted by
      individual protoplasts during the process of regeneration indicate that chitin is
      the first polymer to be laid down, whereas beta (1,3)- and beta (1,6)glucan are
      incorporated at a later stage. Mannoproteins were found on the surface of fresh
      protoplasts and those newly synthesized were then deposited with time. During the
      first steps of wall regeneration, the proteins that interacted covalently with
      chitin or glucan were different, but the same species were found linked to each
      polymer in yeast and mycelial regenerating forms. The aggregates formed by
      regenerating protoplasts were shown to be due to the chitin and mannoprotein
      network initially laid.

PMID- 9765845
TI  - Genotypic diversity and typing of cyanobacterial strains of the genus Arthrospira
      by very sensitive total DNA restriction profile analysis.
AB  - Arthrospira maxima and A. platensis are two species of cyanobacteria cultivated
      and sold as health food, animal feed and source of food additives and fine
      chemicals. The genotypic diversity of several strains attributed to these two
      species on the basis of morphological criteria was investigated using very
      sensitive total DNA restriction profile analysis. The restriction profiles were
      obtained after sodium dodecyl sulphate polyacrylamide gel electrophoresis and
      silver staining. The unweighted pair-group method using arithmetic averages
      applied to the matrix of Dice similarity coefficient values clustered the
      electropherograms of the strains in two well-separated genotypic groups. These
      clusters corresponded to those obtained with morphological criteria. The
      molecular approach used was also able to type the examined strains.

PMID- 9765846
TI  - Genetic and biochemical characterization of Saccharomyces cerevisiae mutants
      resistant to trifluoroleucine.
AB  - Eighteen mutants resistant to 5',5',5'-trifluoroleucine (TFL), a leucine analog,
      were isolated in Saccharomyces cerevisiae strains YNN281 and YNN282. The mutants
      were characterized genetically and clustered in two groups, one comprising all
      the dominant (TFL1) and the other one all the recessive (tfl2) mutations. Genetic
      and biochemical data suggested that the dominant mutations are located on the
      LEU4 gene, coding for alpha-isopropylmalate synthase I. These mutations resulted
      in accumulation of leucine as a consequence of the synthesis of an enzyme
      insensitive to the feedback inhibition by leucine. Leucine excretion in the TFL1
      mutants appeared to be affected by the genetic background of the strain and was
      greatly influenced by lysine metabolism. The measurement of intra- and
      extracellular amino acid concentrations in prototrophic strains carrying TFL1 or
      tfl2 genes showed that both were leucine overproducers. Some of the TFL-resistant
      mutants were tested in alcoholic fermentation of grape must: analysis of the
      fermentation secondary metabolites showed that the major effect of the TFL
      resistant strains was an increased production of isoamyl alcohol compared to that
      of the parental strain.

PMID- 9765847
TI  - The role of the capsular polysaccharide of Aeromonas hydrophila serogroup O:34 in
      the adherence to and invasion of fish cell lines.
AB  - The ability of Aeromonas hydrophila serogroup O:34 strains grown under different
      conditions (capsulated and non-capsulated) to adhere to and invade two fish cell
      lines was compared. The level of adherence was slightly higher when the strains
      were grown under conditions promoting capsule formation than when the same
      strains were grown under conditions which did not promote capsule formation.
      However, the most significant difference among the wild-type strains grown under
      conditions promoting capsule formation was the ability to invade the fish cell
      lines, which was significantly higher than when the same strains were grown under
      conditions which did not promote capsule formation. Isogenic unencapsulated
      mutants grown under conditions promoting capsule formation showed a lower ability
      to invade the fish cell lines than the parental capsulated strains. From these
      results, we concluded that the capsular polysaccharide is an important factor in
      intracellular invasion.

PMID- 9765848
TI  - Molecular epidemiological investigation of Salmonella typhimurium strains related
      to an egg-borne outbreak.

PMID- 9765849
TI  - Participation of host gene functions in plasmid postsegregational killing: how
      and why.

PMID- 9765850
TI  - Universal ribotyping method using a chemically labelled oligonucleotide probe
      mixture.
AB  - Some of the present problems in ribotyping are associated with a lack of uniform
      reactivity of probes when bacterial DNAs are of phylogenetically diverse origins.
      To overcome these problems, a set of five oligonucleotides (referred to as
      OligoMix5) was selected to react with conserved sequences located near both
      extremities of rrs (16S rRNA gene) and near both extremities and the middle of
      rrl (23S rRNA gene). DNA samples from 13 bacterial species selected to represent
      various phylogenetic branches within the Eubacteria were cleaved by a restriction
      endonuclease and electrophoresed in 0.8% agarose, and the fragments were vacuum
      transferred to nylon membranes and hybridized with digoxigenin-labelled
      OligoMix5, plasmid DNA from pKK3535 (cloned rrn operon from Escherichia coli) or
      pBA2 (cloned rrs from Bacillus subtilis), or acetylamino-fluorene-labelled E.
      coli 16 + 23S rRNA. The results showed OligoMix5 to visualize patterns in DNA
      from phylogenetically diverse bacteria with comparable intensity. Banding
      patterns (not band intensity) obtained with OligoMix5 were identical with those
      obtained with 16 + 23S rRNA or plasmid pKK3535 for each strain studied and
      represented complete ribotypes. For DNA from Gram-positive bacteria, complete
      ribotypes were observed after prolonged enzymatic detection of bands when probes
      were either E. coli 16 + 23S rRNA or pKK3535. Patterns given by plasmid pBA2 were
      subsets of the complete ribotypes for 9/13 strains. Each oligonucleotide of the
      OligoMix5 set was used as a probe to determine its contribution to the complete
      ribotype. The five oligonucleotide probes, used individually, visualized one to
      four patterns per DNA sample. Use of DNA from Xenorhabdus sp. CIP 105189 cleaved
      by EcoRI is suggested to control the quality of the oligonucleotide probes
      composing OligoMix5. Probe OligoMix5 was found to be an essential tool for
      ribotyping phylogenetically diverse eubacteria.

PMID- 9765851
TI  - Endo-N-acetyl-beta-D-glucosaminidases and their potential substrates:
      structure/function relationships.
AB  - Endo-N-acetyl-beta-D-glucosaminidases (ENGases) have been defined as the enzymes
      that hydrolyse the glycosidic bond between an N-acetyl-beta-D-glucosamine residue
      and the adjacent (partner) monosaccharide within an oligosaccharide chain. Three
      types of enzymes have been distinguished according to this definition: ENGases
      acting on murein (type I), those acting on chitin (type II) and, finally, those
      acting on N-glycans (type III). Considering that N-acetylmuramic acid is a
      derivative of N-acetylglucosamine (3-O-substituted by a lactyl group), only
      ENGases acting between two N-acetylglucosamine residues are actually known
      despite the fact that other possibilities of partner monosaccharides for N-acetyl
      beta-D-glucosamine are reported. Similarities in the amino acid sequences were
      found to occur only between chitin-ENGases and N-glycan-ENGases, but the
      substrate specificities of these two types of enzymes are different. However, it
      is possible that certain enzymes are able to cleave more than one type of
      substrate, and this could in particular explain why the N-glycan-ENGases are
      largely produced by bacteria in which no potential substrate for this type of
      enzymes was identified. Further study in this area is expected.

PMID- 9765852
TI  - Postantibiotic effect of amikacin, rifampin, sparfloxacin, clofazimine and
      clarithromycin against Mycobacterium avium.
AB  - Antimycobacterial drugs acting efficiently against Mycobacterium avium complex
      have in common low MICs and MBC/MIC ratios. The recently reported clinical
      efficacy of some of the newer drugs is also clearly linked to their
      pharmacokinetic properties such as higher serum level and/or intracellular
      concentrations and half-life. In the present investigation, comparative
      postantibiotic effects (PAEs) of amikacin, rifampin, sparfloxacin, clofazimine
      and clarithromycin were investigated. Bacteria were exposed to MIC, MIC x 4 and
      MIC x 8 concentrations of each drug for 2 h, the drug was removed by
      centrifugation and cells were thoroughly washed and resuspended in drug-free
      medium. Growth was compared to control organisms which underwent a similar
      treatment (but without drugs) and PAEs were assessed using the equation "T-C",
      where T equals the time required for colony counts to increase by 1 log10 in test
      samples after antibiotic exposure and C equals the time for 1 log10 growth in
      control. Our results underlined two distinct patterns concerning PAE: pattern I
      included drugs for which PAE (in hours) was dose-dependent and varied (for MIC,
      MIC x 4 and MIC x 8 concentrations) for amikacin (10.3 +/- 1.7, 14.7 +/- 1.9 and
      17.7 +/- 4.1), rifampin (28.0 +/- 7.6, 62.0 +/- 18.5 and 71.0 +/- 3.2) and
      clarithromycin (2.6 +/- 1.0, 15.0 +/- 4.0 and 22.0 +/- 4.0), whereas pattern II
      included drugs with a stable PAE, relatively independent of the drug
      concentrations: sparfloxacin (11.0 +/- 2.5, 12.3 +/- 6.4 and 13.0 +/- 2.1) and
      clofazimine (26.0 +/- 2.8, 28.8 +/- 2.5 and 27.3 +/- 1.3). These results may be
      useful for guidance in scheduling of drug administration in M. avium-infected
      AIDS patients overburdened with too many drugs given for various opportunistic
      infections.

PMID- 9765853
TI  - Mycobacterium avium complex strains from AIDS patients belong to a homogeneous
      group ascribed by rRNA typing methods.
AB  - 16S rRNA RFLP analysis of Mycobacterium avium complex (MAC) strains isolated from
      25 AIDS patients led to identification of seven ribotypes. The same ribotype was
      determined for strains from 19 patients with and without disseminated disease.
      When isolates representing the seven ribotypes were examined for their internal
      transcribed spacer (ITS) between the 16S and 23S rRNA gene nucleotide sequence,
      four different sequences, including a new ITS type, were recovered. All isolates
      with the most common ribotype belonged to the sequevar Mav-B. When MAC strains
      from AIDS patients were compared by ITS sequencing and ribotyping, a significant
      degree of homogeneity was observed. The discriminatory level reached with
      ribotyping might be useful for grouping isolates from different clinical sources.

PMID- 9765855
TI  - Computer-assisted analysis of Mycobacterium avium fingerprints using insertion
      elements IS1245 and IS1311 in a Caribbean setting.
AB  - A total of 33 clinical isolates of the Mycobacterium avium complex from 25
      patients, identified by means of biochemical and cultural characteristics, the
      Accuprobe system and DT1/DT6 PCR, were further analysed using novel insertion
      elements IS1245 and IS1311 in a French Caribbean setting. PvuII-cleaved DNA and
      non-radioactive Southern hybridization and detection systems were used for
      fingerprinting with both IS elements. The data confirmed the specificity of the
      two probes for M. avium in our setting and highlighted a significant proportion
      of M. intracellulare-infected patients in this region. Two distinct groups
      composed of 2-3 bands and 6-27 bands were found among M. avium isolates, and were
      composed of the same isolates both with IS1245 and IS1311. The computer analysis
      of polymorphic banding patterns identified two prevalent genotypes: one contained
      4 isolates from 3 patients while a second 2-banded cluster was composed of 6
      isolates from 4 patients; all the patients were from the same hospital in
      Guadeloupe. A single isolate from Martinique was falsely included in the 2-banded
      cluster initially upon IS1245 fingerprinting, but could be discriminated from
      other isolates on the basis of IS1311 fingerprinting of PvuII-cleaved DNA. These
      results were also confirmed upon IS1245 fingerprinting of PstI-digested DNA, as
      well as DT6 fingerprinting. A single case of polyclonal infection was also
      discovered in a patient at a 75-day interval. This is the first study comparing
      the two IS elements and constitutes a first description of disseminated M. avium
      complex disease from the Caribbean. We conclude that both elements possess a
      similar discriminatory potential for M. avium isolates. Coupled with computer
      analysis, this methodology would appear to be particularly suitable for larger
      epidemiological studies.

PMID- 9765854
TI  - Borrelia burgdorferi sensu lato in Russia and neighbouring countries: high
      incidence of mixed isolates.
AB  - A total of 365 isolates of Borrelia burgdorferi sensu lato from 12 major
      administrative territories of Russia (from St. Petersburg in the west to South
      Sakhalin in the east) and from the Czech Republic, Estonia, Lithuania,
      Byelorussia, Moldavia, Ukraine and Kirghizia were identified by analysis of
      restriction polymorphism of ribosomal rrf-rrl spacer amplicons. The isolates were
      obtained mainly from ixodes persulcatus and I. ricinus ticks. Other sources
      included small mammals, human patients and I. trianguliceps ticks. The results
      showed that B. garinii (two variants) together with B. afzelii circulated
      throughout the territories studied. The distribution of the variant NT29 of the
      species B. garinii, the most frequently isolated, was associated with that of I.
      persulcatus ticks. B. burgdorferi sensu stricto, and the species B. valaisiana
      and B. lusitaniae (formerly the genomospecies VS116 and PotiB2, respectively)
      were isolated only from I. ricinus ticks in the western part of the studied
      territories. None of these three species were found in 327 isolates from Russia
      where I. persulcatus is the most frequently distributed vector. This work also
      provides evidence for a high incidence of mixed Borrelia infections within
      vectors and hosts (9.3% of isolates were mixtures of Borrelia species). A
      detailed analysis of Borrelia species distribution over the territories studied
      is presented.

PMID- 9765856
TI  - Identification of atypical strains of Staphylococcus epidermidis by use of
      molecular tools.
AB  - Four atypical coagulase-negative staphylococcal (CNS) isolates from clinical
      sources were compared with Staphylococcus epidermidis strains by ribotyping. The
      ribotypes of the four strains shared close rDNA restriction profiles with those
      of the S. epidermidis strains used. The DNA sequence encoding 16S rRNA
      demonstrated 99.9% homology with S. epidermidis. S1 nuclease experiments showed
      that these atypical strains formed a homogeneous genomic group. DNA-DNA
      homologies between the S. epidermidis type strain CCM 2124 and the four CNS
      isolates ranged from 70 to 89%. The guanine-plus-cytosine content of the
      deoxyribonucleic acid of the four strains ranged from 31 to 32 mol%.

PMID- 9765857
TI  - Trinucleotide repeats in yeast.
AB  - The yeast genome exhibits a variety of trinucleotide repeat arrays within protein
      coding genes and intergenic regions. In the first situation, repeats are often
      not random relative to the translational frame, resulting preferably in long
      stretches of the two acidic amino acids or of their corresponding amine forms.
      Interestingly, the longest trinucleotide repeats are often found in genes
      encoding nuclearly located proteins. Repeats tend to be more frequent in long
      genes, but less frequent among members of gene families compared to unique genes.
      In the latter case, repeat arrays often differ in length or composition between
      the gene homologs, indicating their instability.

PMID- 9765858
TI  - Detection of pap, sfa and afa adhesin-encoding operons in uropathogenic
      Escherichia coli strains: relationship with expression of adhesins and production
      of toxins.
AB  - A total of 243 Escherichia coli strains isolated from patients with urinary tract
      infections (UTI) were investigated for the presence of pap, sfa and afa adhesin
      encoding operons by using the polymerase chain reaction. It was found that 54%,
      53% and 2% of the strains exhibited the pap, sfa and afa genotypes, respectively.
      Pap+ and/or sfa+ strains were more frequent in cases of acute pyelonephritis
      (94%) than in cases of cystitis (67%) (P < 0.001) and asymptomatic bacteriuria
      (57%) (P < 0.001). The pap and/or sfa operons were found in 90% of strains
      expressing mannose-resistant haemagglutination (MRHA) versus 37% of MRHA-negative
      strains (P < 0.001). The presence of pap and sfa operons was especially
      significant in strains belonging to MRHA types III (100%) (without P adhesins)
      and IVa (97%) (expressing the specific Gal-Gal binding typical of P adhesins).
      Both pap and sfa operons were closely associated with toxigenic E. coli producing
      alpha-haemolysin (Hly+) and/or the cytotoxic necrotizing factor type 1. There was
      an apparent correlation between the pap and sfa operons and the O serogroups of
      the strains. Thus, 93% of strains belonging to O1, O2, O4, O6, O7, O14, O15, O18,
      O22, O75 and O83 possessed pap and/or sfa operons, versus only 32% of strains
      belonging to other serogroups (P < 0.001). The results obtained in this study
      confirm the usefulness of our MRHA typing system for presumptive identification
      of pathogenic E. coli exhibiting different virulence factors. Thus, 85% of
      strains that possessed both pap and sfa adhesin-encoding operons showed MRHA
      types III or IVa previously associated with virulence of E. coli strains that
      cause UTI and bacteraemia.

PMID- 9765859
TI  - Evidence for a bacteriocin-like substance produced by a new strain of
      Streptococcus sp., inhibitory to gram-positive food-borne pathogens.
AB  - A new strain of Streptococcus sp. (CNCM I-841) isolated from a commercial
      probiotic product was shown to be antagonistic towards several food-borne
      pathogens including Clostridium sp. and Listeria monocytogenes. This strain
      produced and excreted an antibacterial substance in MRS broth. The inhibitory
      substance was different from hydrogen peroxide, since it was unaffected by
      catalase. It was sensitive to proteolytic enzymes, indicating that the active
      moiety of the inhibitor was proteinaceous in nature, and it had no effect on its
      producer strain. These properties suggested that the inhibitory substance could
      be considered as a bacteriocin-like substance. The antimicrobial substance was
      also produced in M17 and tryptose broths if they were supplemented with Tween-80.
      Partial purification allowed a 10.5-fold increase in the specific activity. A
      preliminary characterization showed that it was active against lactobacilli,
      Enterococcus faecalis, Clostridium sp. and Listeria sp. It was not affected by 2
      h treatment at 60 degrees C, but was sensitive to treatments at 100 degrees C and
      to autoclaving at 121 degrees C. The activity was not affected by treatments at
      pH values ranging from 2 to 11.

PMID- 9765860
TI  - Isolation of new plasmids from hyperthermophilic Archaea of the order
      Thermococcales.
AB  - A collection of 57 strains of hyperthermophilic Archaea from the order
      Thermococcales was screened for the presence of plasmids; 9 plasmids present in
      six of these strains were isolated and characterized in terms of size and cross
      hybridization. The Notl macrorestriction patterns of genomic DNA of strains
      harbouring these plasmids were obtained. Pyrococcus abyssi strains GE27 and GE23
      as well as Thermococcus sp. GE31 contained a single plasmid of 3.5 kb (pGN27),
      16.8 kb (pGN23) and 5.3 kb (pGN31), respectively, whilst the three strains I559,
      I560 and I690 all contained two plasmids of 3.5 kb (pSN559, pSN560, pSN690) and
      24 kb (pLN559, pLN560, pLN690), respectively. Plasmid pGN27 strongly cross
      hybridized with the previously described plasmid pGT5 from P. abyssi strain GE5,
      whilst plasmids pGN23 and pGN31 did not cross-hybridize with each other, nor with
      any other plasmid. The three small plasmids of strains I559, I560 and I690 cross
      hybridized, as well as their three large plasmids. Macrorestriction pattern
      analysis and the results of plasmid cross-hybridization experiments indicated
      that these three strains were different but closely related, and likely belonged
      to the genus Thermococcus. This study shows that plasmids are widespread in
      hyperthermophilic archaea, and significantly increases the number and diversity
      of plasmids available for laboratory work.

PMID- 9765861
TI  - PCR-amplified 16S and 23S rDNA restriction analysis for the identification of
      Acinetobacter strains at the DNA group level.
AB  - The genus Acinetobacter is phenotypically rather homogeneous, but genotypically
      heterogeneous. In this study, a simple method based on restriction analysis of a
      PCR-amplified large fragment (4.5 kb) of most of the ribosomal operon (16S and
      23S ribosomal genes and the spacer in-between) was investigated. Sixty-seven
      collection strains belonging to the 20 DNA groups proposed until 1993 were
      studied. Using the enzyme Sau3AI, 25 DNA profiles were obtained. Strains
      belonging to DNA groups 1, 3, 6, TU13 and TU15 showed two profiles each, and DNA
      groups 4, 5 and 7 showed profiles with variants showing less intensive additional
      bands. The remaining 12 groups showed 12 different profiles. The profiles
      obtained were DNA-group-specific except for one profile which was shared between
      the unnamed DNA group 3 and a rarely encountered genotypically related DNA group.
      These two DNA groups could be separated by using the enzyme Hinf1. Twenty-five
      additional clinical isolates previously characterized by standard DNA-DNA
      hybridization were selected in a double-blind fashion for identification at the
      DNA group level to check the reliability of the assay. All strains were correctly
      identified at the DNA group level. PCR-amplified 16S and 23S rDNA restriction
      analysis is both an accurate and rapid method for the identification of
      Acinetobacter at the DNA group level.

PMID- 9765862
TI  - The relationship between microbial metabolic activity and biocorrosion of carbon
      steel.
AB  - The effect of metabolic activity (expressed by generation time, rate of H2S
      production and the activity of hydrogenase and adenosine phosphosulphate (APS)
      reductase enzymes) of the 8 wild strains of Desulfovibrio desulfuricans and of
      their resistance to metal ions (Hg2+, Cu2+, Mn2+, Zn2+, Ni2+, Cr3+) on the rate
      of corrosion of carbon steel was studied. The medium containing lactate as the
      carbon source and sulphate as the electron acceptor was used for bacterial
      metabolic activity examination and in corrosive assays. Bacterial growth
      inhibition by metal ions was investigated in the sulphate-free medium. The rate
      of H2S production was approximately directly proportional to the specific
      activities of the investigated enzymes. These activities were inversely
      proportional to the generation time. The rate of microbiologically induced
      corrosion (MIC) of carbon steel was directly proportional to bacterial resistance
      to metal ions (correlation coefficient r = 0.95). The correlation between the MIC
      rate and the activity of enzymes tested, although weaker, was also observed (r =
      0.41 for APS-reductase; r = 0.69 for hydrogenase; critical value rc = 0.30, p =
      0.05, n = 40).

PMID- 9765863
TI  - Enhanced mineralization of UL-14C-pentachlorophenol by mushroom composts.

PMID- 9765864
TI  - Identification of Rhodococcus, Gordona and Dietzia species using carbon source
      utilization tests ("Biotype-100" strips).
AB  - The "Biotype-100" identification system (BioMerieux, La Balme-Ies-Grottes,
      France) based on carbon source utilization was evaluated for its ability to
      discriminate among 10 species of Rhodococcus, 7 species of Gordona and one
      species of Dietzia. The type strains of three species of Tsukamurella and 8
      species of Nocardia were also included in the study. Results were compared with
      chemotaxonomic and conventional data. Carbon source utilization was shown to be
      reliable, rapid and easy to use when compared with standard identification
      methods. The 29 species tested were unambiguously separated by carbon source
      utilization tests. Rhodococcus equi was found to be heterogenous.

PMID- 9765865
TI  - Supplement 1996 (no. 40) to the Kauffmann-White scheme.
AB  - This supplement reports the characterization of 13 new Salmonella serovars
      recognized in 1996 by the WHO Collaborating Centre for Reference and Research on
      Salmonella: 8 were assigned to S. enterica subsp. enterica, 3 to subspecies
      salamae and 2 to subspecies diarizonae.

PMID- 9765866
TI  - Peptide metabolism in cytoplasm of brain cells.

PMID- 9765867
TI  - Mechanistic and structural studies on methylmalonyl-CoA mutase.

PMID- 9765868
TI  - Swinging arms in multifunctional enzymes and the specificity of post
      translational modification.

PMID- 9765869
TI  - S-adenosylmethionine: a 'poor man's coenzyme B12' in the reaction of lysine 2,3
      aminomutase.

PMID- 9765870
TI  - Enzymes that exploit imines--one way or the other.

PMID- 9765871
TI  - Preparation and properties of 6-substituted cyclohexane-1,2,4-triol derivatives:
      mechanistic probes for the inositol monophosphatase reaction.

PMID- 9765872
TI  - A discussion on the activation of oxygen in chemistry and enzymology.

PMID- 9765874
TI  - Why has phosphatidylethanolamine N-methyltransferase survived in evolution?

PMID- 9765873
TI  - Structure and mechanism of enzymes involved in the assembly of the tetrapyrrole
      macrocycle.

PMID- 9765876
TI  - Activation of calcium-independent phospholipase A2 by depletion of internal
      calcium stores.

PMID- 9765875
TI  - Binding of bee venom and human group IIa phospholipases A2 to membranes: a minor
      role for electrostatics.

PMID- 9765877
TI  - Regulation of cytosolic phospholipase A2 by phosphorylation.

PMID- 9765878
TI  - The structure of phospholipase C isoforms and the regulation of phosphoinositide
      hydrolysis.

PMID- 9765879
TI  - The effects of phospholipid structure on the function of a calcium pump.

PMID- 9765880
TI  - Why is docosahexaenoic acid essential for nervous system function?

PMID- 9765881
TI  - The role of lysophosphatide acyltransferases and protein kinase C isoforms in the
      regulation of lymphocyte responses.

PMID- 9765882
TI  - The non-specific lipid transfer protein (sterol carrier protein 2) acts as a
      peroxisomal fatty acyl-CoA binding protein.

PMID- 9765883
TI  - Anionic phospholipids and the regulation of cell functions.

PMID- 9765884
TI  - Consideration of a phlorin structure for haem P-460 of hydroxylamine
      oxidoreductase and its implications regarding reaction mechanism.

PMID- 9765885
TI  - Dimethylsulphoxide reductase from purple phototrophic bacteria: structures and
      mechanism(s).

PMID- 9765886
TI  - Structural bases for the catalytic mechanism of [NiFe] hydrogenases.

PMID- 9765887
TI  - The diversity of redox proteins involved in bacterial heterotrophic nitrification
      and aerobic denitrification.

PMID- 9765888
TI  - The membrane-integral domain of succinate:quinone oxidoreductases--a secretive
      haem-containing domain.

PMID- 9765889
TI  - The pyrroloquinoline quinone (PQQ)-containing quinoprotein dehydrogenases.

PMID- 9765890
TI  - Structure and function of flavocytochrome c3, the soluble fumarate reductase from
      Shewanella NCIMB400.

PMID- 9765891
TI  - Protein engineering of the photoreaction centre from Rhodobacter sphaeroides.

PMID- 9765892
TI  - Towards structural genomics for transmembrane proteins.

PMID- 9765893
TI  - Molecular dynamics simulations of membranes with embedded proteins and peptides:
      porin, alamethicin and influenza virus M2.

PMID- 9765894
TI  - Helical structure and dynamics in membrane polypeptides.

PMID- 9765895
TI  - Three-dimensional models of glutamate receptors.

PMID- 9765896
TI  - Fibrillogenesis of beta-amyloid.

PMID- 9765897
TI  - Intraneuronal filamentous tau protein and alpha-synuclein deposits in
      neurodegenerative diseases.

PMID- 9765898
TI  - Polyglutamine expansion and Huntington's disease.

PMID- 9765899
TI  - Copper, zinc superoxide dismutase (SOD1) and its role in neuronal function and
      disease with particular relevance to motor neurone disease/amyotrophic lateral
      sclerosis.

PMID- 9765900
TI  - The three-dimensional structure of prion protein: implications for prion disease.

PMID- 9765901
TI  - Amyloid fibres of Sup35 support a prion-like mechanism of inheritance in yeast.

PMID- 9765902
TI  - Presenilins--in search of functionality.
AB  - The discovery of the PS proteins, the complexities of their biochemistry and
      their potential involvement in signalling pathways and in apoptosis have
      galvanized research into AD. To date, the aspect of the functionality of the PSs
      most relevant to the pathology of AD is the effect of PS FAD mutants to increase
      the proportion of A beta 42 produced from cells. This, coupled to the observation
      that gamma-secretase cleavage is considerably reduced in neurons derived from PS
      1 knockout mice, argues strongly that PS plays a very direct role in the
      proteolytic processing of APP.

PMID- 9765903
TI  - The Fe65 and X11 families of proteins: proteins that interact with the
      Alzheimer's disease amyloid precursor protein.

PMID- 9765904
TI  - Characterization of beta-secretase.

PMID- 9765905
TI  - Transgenic mouse models of Alzheimer's disease.

PMID- 9765906
TI  - Modelling the packing of transmembrane helices: application to aquaporin-1.

PMID- 9765907
TI  - Studies on the structure of a transmembrane region and a cytoplasmic loop of the
      human red cell anion exchanger (band 3, AE1).

PMID- 9765908
TI  - Structure of the G-protein-coupled receptor, rhodopsin: a domain approach.

PMID- 9765909
TI  - Mechanistic aspects of energy coupling in the Escherichia coli mannitol
      phosphotransferase system: a domain approach.

PMID- 9765910
TI  - How cytidylyltransferase uses an amphipathic helix to sense membrane phospholipid
      composition.
AB  - CT responds to properties of PC-depleted membranes: increased negative charge
      density, which concentrates the enzyme at the membrane surface, and lipid packing
      perturbations, which create holes in the membrane surface into which the
      hydrophobic side chains of the amphipathic helix of domain M can intercalate. The
      PC-deficient lipid surface appears capable of catalysing the folding of domain M
      into an alpha-helix. The determinants on domain M which create a preference for
      anionic lipids are: (i) strips of interfacial lysines; (ii) three serines within
      the non-polar face; (iii) three interfacial glutamates whose protonation state
      appears to be sensitive to the surface charge. Phosphorylation of the domain
      adjacent to domain M decreases the membrane affinity of the amphipathic helix,
      perhaps by an ion-pairing competition. The mechanism whereby the stabilization of
      an alpha-helical conformation of domain M is transduced into a conformational
      change in the catalytic domain is the key question for future exploration.

PMID- 9765911
TI  - The role of heparin in the complex formation between fibroblast growth factor 2
      and its high affinity receptor: comparative modelling and biochemical studies.

PMID- 9765912
TI  - Using HOLE to predict the effects of PEG's on the conductance of alpha-toxin.

PMID- 9765914
TI  - Dynamic properties of ions in models of ion channels studied by molecular
      dynamics simulation.

PMID- 9765913
TI  - Studies on the transmembrane domain of phospholamban using rotational resonance
      and magic angle oriented sample spinning (MAOSS) NMR spectroscopy.

PMID- 9765915
TI  - Assessment of 'Metabolism' in an integrated medical curriculum.

PMID- 9765916
TI  - Conductimetry for enzyme teaching.

PMID- 9765917
TI  - Extracellular signal-regulated kinase 1 or 2 activation by Fc gamma RI
      aggregation in U937 cells.

PMID- 9765918
TI  - Ectopic expression of natural resistance-associated macrophage protein-1 in COS-1
      cells modulates iron accumulation.

PMID- 9765919
TI  - Fc-dependent immune regulation. Enhancement and/suppression directed by antibody
      engaging functional Fc receptors (FcR).

PMID- 9765920
TI  - Characterization of the Fc receptors (FcR) functioning as bridge between antibody
      and cell-effector function: antibody-FcR-linked activation of immune
      responsiveness.

PMID- 9765921
TI  - Fc gamma receptors in negative signaling--as potential candidates for the
      antibody induced regulation of humoral responses.

PMID- 9765922
TI  - Leptin regulation of expression of neuropeptide Y and its receptor.

PMID- 9765923
TI  - Effect of endotoxin on very-low-density lipoprotein metabolism in rat heart.

PMID- 9765924
TI  - delta-Aminolevulenic acid (ALA) and the control of intestinal iron absorption.

PMID- 9765925
TI  - Growth hormone regulation of mammary glucose.

PMID- 9765926
TI  - Tissue-specific differences in rat glucocorticoid receptor gene transcriptional
      regulation.

PMID- 9765927
TI  - Heterotrophic nitrification in Paracoccus denitrificans.

PMID- 9765928
TI  - Modification of the binding pocket for the QA ubiquinone in the reaction centre
      from Rhodobacter sphaeroides.

PMID- 9765929
TI  - Molecular structure of an unusual cytochrome c2 determined at 2.0 A; the
      cytochrome cH from Methylobacterium extorquens.

PMID- 9765930
TI  - Stopped-flow studies on dimethylsulphoxide reductase from Rhodobacter capsulatus:
      kinetic competence of the dimethylsulphide-reduced intermediate.

PMID- 9765931
TI  - The interaction of eukaryotic cytochrome b5 with flavocytochrome P-450 BM3 from
      Bacillus megaterium.

PMID- 9765932
TI  - Mechanistic probes of flavocytochrome P-450 BM3.

PMID- 9765933
TI  - Electron-transferring flavoprotein from Megasphaera elsdenii; gene organisation
      and structural information.

PMID- 9765934
TI  - Characterization of the complex of isoFMN and apoflavodoxin from Desulfovibrio
      vulgaris (Hildenborough).

PMID- 9765935
TI  - The nrfEFG gene products are required for the activity of the cytochrome c552
      nitrite reductase from Escherichia coli.

PMID- 9765936
TI  - The periplasmic nitrate reductase of Escherichia coli--a comparison with the Nap
      systems of other bacteria.

PMID- 9765938
TI  - Cell proliferation and CTP:cholinephosphate cytidylyltransferase activity in
      higher plants.

PMID- 9765937
TI  - Sexual dimorphism in the fatty acyl composition of rat adrenal lipids.

PMID- 9765939
TI  - Role of lipid peroxidation in the testicular damage in experimentally varicocele
      induced rats.

PMID- 9765940
TI  - Relationship between serum fatty acids and malondialdehyde (MDA) levels in
      coronary artery disease diagnosed (CAD) patients.

PMID- 9765941
TI  - S phase depletion of nuclear CTP:choline phosphate cytidylyltransferase.

PMID- 9765942
TI  - Chromatin-associated phosphatidylcholine synthesis.

PMID- 9765943
TI  - Diethylstilbestrol antagonizes the oxidant-induced transformations of membrane
      phospholipids.

PMID- 9765944
TI  - BipA affects Ca++ fluxes and phosphorylation of the translocated intimin receptor
      (Tir/Hp90) in host epithelial cells infected with enteropathogenic E. coli.

PMID- 9765945
TI  - Analysis of phosphatidic acid molecular species using mass spectrometry.

PMID- 9765946
TI  - Molecular species of acidic phospholipids in human lung surfactant.

PMID- 9765948
TI  - Effects of sphingosine 1-phosphate and bradykinin on phospholipid signalling in
      human epithelial A549 cells.

PMID- 9765947
TI  - Interaction of the SR CaATPase with the cytoplasmic region of phospholamban.

PMID- 9765949
TI  - Modulation of CTP:phosphocholine cytidylyltransferase by membrane torque tension.

PMID- 9765950
TI  - The okadaic acid induced ACAT activation is prevented by a specific inhibitor of
      the Ca2+/calmodulin protein kinase II.

PMID- 9765951
TI  - Expression of FAT, the putative fatty acid translocator protein, is
      developmentally regulated in rat mammary tissue.

PMID- 9765952
TI  - Activation of phospholipase A2 during differentiation of human haemopoietic
      progenitor cells.

PMID- 9765953
TI  - Anionic lipids and accumulation of Ca2+ by a Ca(2+)-ATPase.

PMID- 9765954
TI  - Adrenaline induced inhibition of neutrophil PLA2 activity.

PMID- 9765955
TI  - Phospholipase D enhances the hydrolysis of phospholipid vesicles by cytosolic
      phospholipase A2.

PMID- 9765956
TI  - Lipoprotein lipase hydrolysis of human lipoproteins measured using a fluorescence
      displacement assay.

PMID- 9765957
TI  - Liver fatty acid binding protein (FABP) binds to anionic phospholipid vesicles
      with release of ligand.

PMID- 9765958
TI  - Purification and properties of an active site mutant, H48Q, of human non
      pancreatic secreted phospholipase A2.

PMID- 9765959
TI  - beta-Amyloid toxicity in rat brain reaggregate cultures.

PMID- 9765960
TI  - Detergent solubility and processing of the familial Alzheimer's disease-related
      presenilin proteins.

PMID- 9765961
TI  - The amyloid precursor protein (APP) and the angiotensin converting enzyme (ACE)
      secretase are inhibited by hydroxamic acid-based inhibitors.

PMID- 9765962
TI  - Full length huntingtin is not detected in intranuclear inclusions in Huntington's
      disease brain.

PMID- 9765963
TI  - Blood platelets do not contain the low-density receptor-related protein (LRP).

PMID- 9765964
TI  - Molecular characterisation of the Alzheimer's amyloid precursor protein
      secretases.

PMID- 9765965
TI  - Stimulation of glyceraldehyde-3-phosphate dehydrogenase by oxyhemoglobin.

PMID- 9765966
TI  - Soybean iron metabolism and nutrition.

PMID- 9765967
TI  - The cloning and functional expression of human pancreatic aminopeptidase P.

PMID- 9765968
TI  - Affinity purification of human IgG using immobilised, mutated immunoglobulin
      binding domains from protein A of Staphylococcus aureus.

PMID- 9765969
TI  - A chaperonin apical domain from the thermophilic bacterium Thermus Aquaticus.

PMID- 9765970
TI  - Aluminosilicate particulate and beta-amyloid in vitro interactions: a model of
      Alzheimer plaque formation.

PMID- 9765971
TI  - Transcription factor, BTF3, and the AF-1 function of the estrogen receptor.

PMID- 9765972
TI  - Regulation of macrophage lipoprotein lipase by cytokines.

PMID- 9765973
TI  - Use of an antisense strategy to dissect the role of MAP kinases in cellular
      signalling.

PMID- 9765975
TI  - Pax-3: a role in embryonic cell division, cell morphology or neuronal
      differentiation?

PMID- 9765974
TI  - Role of CBP in glucocorticoid-induced gene repression.

PMID- 9765976
TI  - Regulation of the paired box transcription factor Pax-3.

PMID- 9765977
TI  - Regulation of herpes simplex virus immediate early gene expression.

PMID- 9765978
TI  - Programmed cell death in skeletal muscle.

PMID- 9765979
TI  - Glucose-dependent decreased DNA synthesis in bovine retinal endothelial cells is
      mediated by protein kinase C iota.

PMID- 9765980
TI  - DNA triple helix formation at (AT)n tracts.

PMID- 9765981
TI  - Archaeal evidence for the role of 2' aminoacylation of RNA in the origin of amino
      acid homochirality.

PMID- 9765982
TI  - A proposed mechanism for the induction of activator protein 1 (AP-1) binding by
      HIV-1 negative factor(Nef) in the macrophage cell line RAW267.4 cells.

PMID- 9765983
TI  - Molecular cloning and characterisation of a novel duodenal-specific gene
      implicated in iron absorption.

PMID- 9765984
TI  - Identification of a novel PKD1 mutation in an Irish autosomal dominant polycystic
      kidney disease kindred.

PMID- 9765985
TI  - Studies of gene expression patterns in RER+ and RER- colon cancer cell lines.

PMID- 9765986
TI  - Fibre type-specific expression of the calpain proteolytic system in skeletal
      muscle.

PMID- 9765987
TI  - Characterisation of 8-amino-7-oxononanoate synthase: a bacterial PLP-dependent,
      acyl CoA condensing enzyme.

PMID- 9765988
TI  - Cysteine conjugate beta-lyase activity of amino acid decarboxylases.

PMID- 9765990
TI  - An investigation of flavoprotein redox partners.

PMID- 9765989
TI  - Site-directed mutagenesis of the quinoprotein glucose dehydrogenase of
      Escherichia coli; the role of His262 in PQQ binding and determination of
      substrate specificity.

PMID- 9765991
TI  - Chemical modification of histidine residues in human 'electron transferring
      flavoprotein' (ETF).

PMID- 9765992
TI  - Structure and function studies of oxalate oxidase.

PMID- 9765993
TI  - Availability in pooled normal blood plasma of activated Hageman factor and
      kallikrein for contact induced coagulation.

PMID- 9765994
TI  - Two glycolytic enzymes from Sulfolobus solfataricus.

PMID- 9765995
TI  - Degradation rates differ between mutant and wild-type forms of phenylalanine
      hydroxylase expressed in vitro.

PMID- 9765996
TI  - Identification of subunit interfaces of glycerol dehydrogenase from Bacillus
      stearothermophilus.

PMID- 9765997
TI  - Studies on the folding and unfolding of glycerol dehydrogenase from Bacillus
      stearothermophilus.

PMID- 9765998
TI  - Characterisation of domain fragments of recombinant human albumin.

PMID- 9765999
TI  - Expression of recombinant aroB-encoded dehydroquinate synthase from pathogenic
      microorganisms.

PMID- 9766000
TI  - Site-directed mutants of the catalase-peroxidase from Mycobacterium tuberculosis.

PMID- 9766001
TI  - Construction of a Pseudomonas aeruginosa cosmid library.

PMID- 9766002
TI  - Molecular modelling of batroxobin on kallikreins.

PMID- 9766004
TI  - Mechanistic studies on E.coli 5-aminolaevulinic acid dehydratase.

PMID- 9766003
TI  - Incubation of 6-methylsalicylic acid synthase with alternative starter units in
      the absence of NADPH and the identification of the resulting triaceticacid
      lactones.

PMID- 9766005
TI  - Dipyrromethane cofactor assembly in porphobilinogen deaminase.

PMID- 9766006
TI  - Cloning, isolation, expression and mutagenesis studies on the human immuno
      deficiency virus type 1 (HIV-1) protease.

PMID- 9766007
TI  - Over-expression of the N-terminal domain of the glucagon-like peptide-1 receptor
      in Escherichia coli.

PMID- 9766009
TI  - The effects of thimerosal on the purified InsP3 receptor.

PMID- 9766010
TI  - Cross-linking analysis of rabbit skeletal muscle dystrophin.

PMID- 9766008
TI  - Role of Glut1 glucose transporter activation in stimulation of glucose transport
      by A231876 and TPA.

PMID- 9766011
TI  - Oligomerisation of calsequestrin from rabbit skeletal muscle.

PMID- 9766013
TI  - Localisation and dynamics of receptor-insulin contacts by NMR studies on the
      human insulin receptor ectodomain.

PMID- 9766014
TI  - Use of cross-linking to investigate protein interactions with E. coli penicillin
      binding protein 4.

PMID- 9766012
TI  - Cellular localisation of the most common mutant form of the CF gene protein,
      delta F508-CFTR.

PMID- 9766016
TI  - Solid state NMR studies of ligands bound to the nicotinic acetylcholine receptor.

PMID- 9766015
TI  - An investigation into the lipid interactions of peptides corresponding to the C
      terminal anchoring domains of Escherichia coli penicillin-binding proteins 4 and
      5.

PMID- 9766017
TI  - Localization of endoplasmic reticulum in living cells using green fluorescent
      protein chimeras.

PMID- 9766018
TI  - Identification of endoplasmic reticulum targeting signals using SERCA/PMCA
      chimeras.

PMID- 9766019
TI  - Electrostatics of ligand-gated ion channels.

PMID- 9766020
TI  - Molecular dynamics of ion/channel interactions.

PMID- 9766021
TI  - Peptide-bilayer interactions:- simulation studies.

PMID- 9766022
TI  - Simulations of the M2 channel for influenza A virus.

PMID- 9766023
TI  - Cell-free synthesis and assembly of connexins into functional gap junction
      hemichannels.

PMID- 9766024
TI  - The effect of mastoparan on the E2-E1 transition of the SR Ca(2+)-ATPase.

PMID- 9766025
TI  - Effect of the D32N and N300F mutations on the activity of the bacterial sugar
      transport protein, GalP.

PMID- 9766026
TI  - Interaction of calpastatin isoforms with L-type Ca2+ channels.

PMID- 9766027
TI  - Structure and conformation of the retinal chromophore in bovine rhodopsin.

PMID- 9766028
TI  - Transmembrane alpha-helices in phospholipid bilayers.

PMID- 9766029
TI  - Flexible hinges in dystrophin.

PMID- 9766030
TI  - Why inject contrast for magnetic resonance angiography?

PMID- 9766031
TI  - Future directions of magnetic resonance angiography.

PMID- 9766032
TI  - Determinants of image appearance in contrast-enhanced magnetic resonance
      angiography. A review.
AB  - The use of contrast agents in magnetic resonance (MR) studies of vascular
      pathology has permitted the exploration of regions that were heretofore poorly
      evaluated with conventional magnetic resonance angiography (MRA). An important
      feature of contrast-enhanced MRA (CE-MRA) is the very short acquisition times
      that are possible. The determination of the parameters to be used in a CE-MRA
      study rests on an understanding of the dynamics of the passage of the injected
      contrast agent and the response of the magnetization to the parameters of the MR
      imaging sequence. An overview of this interaction is presented.

PMID- 9766033
TI  - X-ray digital subtraction angiography to magnetic resonance-digital subtraction
      angiography using three-dimensional TRICKS. Historical perspective and computer
      simulations: a review.
AB  - Seventeen years after the introduction of x-ray digital subtraction angiography
      (DSA), gadolinium-enhanced magnetic resonance (MR) angiography techniques have
      become available for the performance of MR-DSA. For the purposes of this article,
      we will consider this to include two-dimensional and three-dimensional approaches
      using time-resolved and non-time-resolved applications. Magnetic resonance-DSA is
      one in a historical progression of techniques which have aimed to produce less
      invasive forms of angiography. After outlining some historical milestones,
      several current issues regarding current methods for MR-DSA are discussed.

PMID- 9766034
TI  - Arterial-phase three-dimensional gadolinium magnetic resonance angiography of the
      renal arteries. Strategies for timing and contrast media injection: original
      investigation.
AB  - RATIONALE AND OBJECTIVES: The authors review different imaging and contrast-media
      infusion strategies for arterial-phase three-dimensional (3D) gadolinium-enhanced
      magnetic resonance angiography (Gd-MRA). METHODS: The influence of
      physicochemical factors on the infusion of contrast media, including viscosity,
      flow rate, inline pressure, and cannula size, is assessed. The combination of
      manual or automated contrast-media administration with timing-dependent or 
      independent 3D Gd-MRA techniques is reviewed regarding the aspects of
      effectiveness, robustness, image quality, and costs. RESULTS: For effective bolus
      delivery with high flow rates, the type and temperature of the contrast media,
      the size of the cannula, and an immediate saline flush must be considered. Timing
      dependent techniques based on a test bolus and using automated contrast-media
      infusion as well as timing independent techniques such as MR SmartPrep or
      multiphase 3D Gd-MRA by using a manual injection with a SmartSet tubing set, are
      all effective procedures for arterial phase 3D Gd-MRA. CONCLUSIONS: Manual
      contrast-media injection with a tubing set can be used for timing-independent MRA
      techniques. The multiphase 3D Gd-MRA approach seems to be favorable for different
      MR systems, robustness, and speed.

PMID- 9766035
TI  - Optimization of gadolinium-enhanced magnetic resonance angiography using an
      automated bolus-detection algorithm (MR SmartPrep). Original investigation.
AB  - Gadolinium (Gd)-enhanced three-dimensional (3D) magnetic resonance angiography
      (MRA) is a quick method for performing noninvasive diagnostic angiography. A
      major technical obstacle to the successful implementation of this technique,
      however, is the proper coordination of the data acquisition with the contrast
      bolus. In this article, the use of an automated bolus-detection algorithm (MR
      SmartPrep), which triggers the initiation of data acquisition for Gd-enhanced 3D
      MRA is reviewed. Potential applications of this evolving technique are
      illustrated.

PMID- 9766036
TI  - Contrast-enhanced magnetic resonance angiography. Potential applications and
      pitfalls in magnetic resonance angiography-guided therapy: a review.

PMID- 9766037
TI  - Optimizing three-dimensional gadolinium-enhanced magnetic resonance angiography.
      Original investigation.
AB  - RATIONALE AND OBJECTIVES: This primarily theoretical work examines three
      dimensional gadolinium-enhanced magnetic resonance angiography f8p4Gd-MRA) with
      the goal of understanding how to achieve the best possible images with respect to
      signal to noise ratio (SNR) and k-space induced artifacts. Patient variables,
      contrast injection schemes, and pulse sequence parameters are considered for this
      purpose. METHODS: A theoretical analysis, including computer simulation,
      describes how contrast material injection profiles influence 3D Gd-MRA images,
      both in terms of intravascular signal and resultant artifacts. Further
      theoretical analysis of the spoiled gradient refocused pulse sequence describes
      how to maximize SNR. Clinical imaging complements computer modeling. RESULTS:
      Equations were derived relating contrast injection parameters and pulse sequence
      variables to SNR and artifacts. For present imaging equipment, administering
      contrast material over a duration of 60% to 80% of the total imaging time and
      using fractional echo techniques gives the best SNR without significantly
      sacrificing image quality. CONCLUSIONS: Three-dimensional Gd-MRA can be tailored
      to a specific clinical situation and imaging system through the use of proper
      breath-holding, bolus timing, Gd administration, and pulse sequence design.

PMID- 9766038
TI  - Contrast-enhanced magnetic resonance angiography of peripheral vessels. Different
      contrast agent applications and sequence strategies: a review.
AB  - In this article the relation between contrast medium (CM) application and
      sequence parameters will be discussed with respect to clinical use of the
      contrast-enhanced magnetic resonance angiography (CE-MRA) in the peripheral
      vessel region. The adjustment of the sequence parameters, the CM application
      timing and the bolus geometry is necessary for an effective use of CE-MRA.
      Investigation protocols for several vascular regions differ mainly corresponding
      to varying fields of view and slab thickness. Restrictions of increasing the
      measurement time are expected in peripherally localized vessels if fast
      arteriovenous transit time occurs. The vessel contrast depends from (1) optimal
      CM bolus timing and (2) bolus geometry defined by the parameters of the
      intravenous bolus injection (flow rate, dose and NaCl flush volume). Our study
      results have shown that the bolus remains compact but also shorter if a higher
      flow rate is being applied at equal dose. The enlargement of the NaCl flush
      volume has evidently caused an increased intraarterial CM concentration and a
      slightly bolus lengthening. The exact timing regimen requires an automated
      mechanical CM injection pump. In most countries, a total dose of 0.3 mmol/kg Gd
      is allowed for application during one investigation. Therefore, obtaining an
      angiogram of the entire iliac and leg region this total dose must be separated.
      0.1 mmol/kg for each of the three measurements can be recommended. Otherwise,
      using this lower CM dose results in less spatial resolution. At least a dosage of
      0.2 mmol/kg Gd is necessary to achieve a higher spatial resolution. The
      calculation of CM dosage should be also related to the dedicated vessel region of
      interest than to the body weight only.

PMID- 9766039
TI  - Technology assessment of magnetic resonance angiography. Why pretty pictures are
      not enough: an overview.

PMID- 9766040
TI  - Patient preference for magnetic resonance versus conventional angiography.
      Assessment methods and implications for cost-effectiveness analysis: an overview.

PMID- 9766041
TI  - Contrast-enhanced magnetic resonance angiography of cerebral arteries. A review.
AB  - The loss of blood vessel visibility due to the signal saturation of slow flow can
      be partially overcome by the T1 reduction that occurs with the use of contrast
      agents such as Gd-DTPA during magnetic resonance angiography (MRA) studies.
      Dynamic-imaging techniques that have been applied successfully in abdominal
      imaging may also be useful for intracranial applications. However, the time
      between arterial and venous enhancement is very short during intracranial
      circulation. This limits the spatial resolution that can be obtained between
      arterial and venous enhancement. Fortunately, the blood-brain barrier and the
      relatively long duration of significant decrease in blood T1 has led to the
      development of very high resolution intracranial MRA techniques. Knowledge of the
      contrast-agent dilution factors and the ultimate resulting relaxation rates can
      be used to optimize the imaging parameters to maximize vessel signal relative to
      the background signal (the signal-difference-to-noise ratio). The additional
      venous vascular detail in the contrast-enhanced study can be spatially resolved
      in the 3D image data and determined by incorporating information from both high
      resolution precontrast and postcontrast studies. In this article, the history,
      development and application of contrast agents in MRA are presented.

PMID- 9766042
TI  - Contrast-enhanced magnetic resonance angiography of the cervical arteries. A
      review.

PMID- 9766043
TI  - Contrast-enhanced magnetic resonance imaging of the coronary arteries. A review.
AB  - The advent and continued improvement of T1-shortening contrast media have
      revolutionized magnetic resonance angiography (MRA) of the entire body in recent
      years. The technical basis for contrast-enhanced MRA is fast three-dimensional
      (3D) imaging. A brief historic review of the technical advances in MR coronary
      artery imaging clearly points to the importance of improved gradient capabilities
      that led to the development and wide application of fast 3D imaging. The use of
      contrast agents in coronary artery imaging has been expected for many years,
      given its success in other parts of the body. Nevertheless, because of the
      potential difficulties and unique characteristics of fast 3D imaging in the
      heart, the utility of contrast agents in coronary artery imaging has been
      systematically investigated only in the last 2 years. Initial experience from our
      group and others showed that contrast agents have great potential in pushing MR
      coronary artery imaging to a much higher level in terms of speed and signal-to
      noise ratio (SNR), and intravascular agents are more desirable than extracellular
      agents. Nevertheless, because of the technical challenges and the diversity of
      methods used for coronary artery imaging, much more effort is needed to continue
      to improve the imaging techniques and further to define the roles of contrast
      agents in coronary artery imaging.

PMID- 9766044
TI  - Gadolinium-enhanced three-dimensional magnetic resonance angiography of the
      thoracic aorta and arch vessels. A review.

PMID- 9766045
TI  - Contrast-enhanced magnetic resonance angiography of the pulmonary vasculature. A
      review.
AB  - Magnetic resonance angiography (MRA) has been established as a powerful
      noninvasive imaging modality. Its applications to the study of the pulmonary
      vasculature have been hampered by a multitude of factors, such as respiratory and
      cardiac motion artifacts, saturation problems, long acquisition times, and
      limited spatial resolution. The recent introduction of contrast-enhanced MRA (CE
      MRA) has greatly improved the potential for possible investigation of the
      pulmonary arteries under clinical conditions. Three-dimensional sequences with
      minimum TR and TE, a flip angle between 20 degrees and 60 degrees, and minimum
      slice thickness can be considered an optimal approach for breath-hold imaging
      combined with the automatic injection of contrast medium. Early studies have
      demonstrated the superiority of CE-MRA over nonenhanced techniques. The major
      indication for CE-MRA of the pulmonary vasculature is pulmonary embolism. Here a
      sensitivity of 85% and specificity of 95% can be obtained. It can be complemented
      by perfusion imaging, ventilation imaging, functional measurements of the right
      ventricle, and MR venography of the pelvic and femoral veins. Blood pool contrast
      agents will open new perspectives in the future. This article reviews the
      technical aspects of CE-MRA of the pulmonary vasculature, pathologic findings,
      and their interpretation as well as present and future clinical applications.

PMID- 9766046
TI  - Gadolinium-enhanced magnetic resonance angiography of the aorta. A review.

PMID- 9766047
TI  - Portal venous magnetic resonance angiography. A review.

PMID- 9766048
TI  - Differences in predominant enhancement mechanisms of superparamagnetic iron oxide
      and ultrasmall superparamagnetic iron oxide for contrast-enhanced portal magnetic
      resonance angiography. Preliminary results of an animal study original
      investigation.
AB  - RATIONALE AND OBJECTIVES: To determine the effect of particle size of
      superparamagnetic iron oxide (SPIO) contrast agents on magnetic resonance
      angiography of the portal venous system. METHODS: We studied eight beagle dogs by
      a T1-weighted 3D turbo-gradient echo magnetic resonance (MR) angiography sequence
      (TE 4 milliseconds, TR 11 milliseconds, flip angle 25 degrees, coronal imaging
      plane) before and after administration of either Resovist (SHU555A), a
      superparamagnetic iron oxide contrast agent with a mean particle size of 60 nm
      and a relaxivity ratio R2/R1 of approximately 7, or a new ultrasmall
      superparamagnetic iron oxide (USPIO) contrast agent with a mean particle size of
      approximately 20 nm and a R2/R1 ratio of approximately 2. Images were acquired on
      a 1.5-T MR body scanner. Both agents were injected as a peripheral bolus of 40
      mumol Fe/kg body weight. Repeated scans were acquired before, immediately after,
      and 10, 20, 30, and 40 minutes after administration of the agent. RESULTS: After
      administration of Resovist, portal venous signal increased to 237% of control
      immediately after injection, while hepatic parenchymal signal intensity decreased
      to 86% of control. The maximal CNR increase to 177% was achieved immediately
      after injection of the agent. After USPIO, portal venous signal increased to 401%
      of the precontrast value immediately after injection, while hepatic parenchymal
      signal intensity also increased to 131% of control at this time. Hepatic signal
      then decreased progressively to 49% of control after 40 minutes. The maximal CNR
      increase to 326% was achieved 10 minutes after injection of the agent.
      CONCLUSIONS: It is concluded that superparamagnetic iron oxide particles of
      different sizes have different R2/R1 ratios and, consequently, different
      mechanisms of contrast improvement in T1-weighted portal MR angiograms.

PMID- 9766050
TI  - Contrast-enhanced magnetic resonance angiography of the renal arteries. Original
      investigation.
AB  - RATIONALE AND OBJECTIVES: The authors determine the value of contrast-enhanced,
      three-dimensional (3D) magnetic resonance angiography (MRA) in the assessment of
      the renal arteries in comparison with conventional arteriography (CA). METHODS:
      One hundred three patients (71 m, 32 f) were evaluated with both CA and 3D MRA.
      The 3D MRA data set consisted of 44 contiguous sections, acquired in apnea (23-28
      seconds) using the following parameters: TR/TE 3.9/1.5 milliseconds, flip angle
      40 degrees to 50 degrees, 3/4 k-space acquisition. A bolus of 0.3 mmol/kg BW
      gadolinium-DTPA was administered intravenously, using an automated injector. A
      test bolus method was used for timing of the bolus relative to the beginning of
      the data acquisition. Intra-arterial CA was used as the standard of reference in
      all patients. Separate interpretations of the CA and MRA results were made by two
      different pairs of radiologists, who were each blinded to the results of the
      other exam. RESULTS: In all, 31 of 33 accessory renal arteries were correctly
      identified. All 205 main renal arteries were seen with MRA. Of 65 significant
      stenoses identified on CA, 61 were correctly identified and graded by MRA.
      Sensitivity and specificity values for the assessment of significant renal
      arterial lesions were 93% and 90%, respectively. CONCLUSIONS: Breath-hold,
      contrast-enhanced 3D MRA allows for the reliable assessment of renal arterial
      morphology and pathologic states.

PMID- 9766049
TI  - Gadolinium-enhanced magnetic resonance venography of the portal venous system
      prior to transjugular intrahepatic portosystemic shunts and liver
      transplantation. Original investigation.
AB  - RATIONALE AND OBJECTIVES: The accuracy of gadolinium-enhanced magnetic resonance
      venography (GdMRV) in identifying visceral venous abnormalities was assessed in
      patients before they underwent transjugular intrahepatic portosystemic shunt
      (TIPS) or orthotopic liver transplantation (OLT). METHODS: Twenty-seven patients
      with portal hypertension underwent GdMRV and transcatheter venography prior to
      OLT or TIPS. The gadolinium dose was 0.5 mL/kg (0.25 mmol/kg), administered by
      rapid hand injection. Coronal 3D spoiled gradient-echo GdMRV was performed in a
      single breath-hold. Four blinded reviewers retrospectively evaluated coronal
      maximum intensity projection (MIP) images, while two reviewers evaluated the MIPs
      and multiplanar reconstructions. Abnormalities that could affect transjugular
      intrahepatic portosystemic shunt or transplantation were noted and compared with
      the results of corresponding catheter venograms read by a separate blinded
      reviewer. RESULTS: Abnormalities were identified by GdMRV with a sensitivity and
      specificity of 83% and 97% for the right hepatic vein, 86% and 100% for the main
      portal vein (MPV), 42% and 99% for the right portal vein, 54% and 94% for the
      left portal vein, 61% and 96% for the superior mesenteric vein, and 74% and 91%
      for the splenic vein. Varices and shunts were correctly identified with a
      sensitivity of 96%. Multiplanar reconstruction increased MPV sensitivity to 100%.
      CONCLUSION: Vascular abnormalities that affect TIPS and OLT can be identified by
      GdMRV. Multiplanar reconstruction increased the accuracy to 100% for the MPV.

PMID- 9766051
TI  - Renal anatomic changes on magnetic resonance imaging and gadolinium-enhanced
      magnetic resonance angiography after renal revascularization. Original
      investigation.
AB  - RATIONALE AND OBJECTIVES: The anatomic and hemodynamic renal changes after renal
      arterial revascularization (RAR) were investigated. METHODS: Thirty-seven kidneys
      and 40 renal arteries were evaluated in 20 patients by using magnetic resonance
      imaging/magnetic resonance angiography (MRI/MRA) to assess pre- and post-RAR
      renal length and mass, parenchymal thickness, renal enhancement, renal artery
      caliber, poststenotic dilation, and signal dephasing on 3D phase contrast (PC).
      The kidneys and renal arteries were segregated into three groups. Group 1
      included 16 patients who benefited from RAR (defined as clinical improvement
      based on decreased serum creatinine or fewer number of antihypertensive
      medications) in whom 26 renal arteries in 25 kidneys were studied. Intervention
      included renal artery endarterectomy (n = 20); aortorenal bypass (n = 3); renal
      artery reimplantation (n = 3); and percutaneous transluminal angioplasty (PTA; n
      = 1). A total of 27 interventions was performed, as PTA failed for one patient
      who subsequently underwent aortorenal bypass before reimaging. Group 2 included
      four patients who did not clinically benefit. A total of eight revascularized
      arteries were studied in seven kidneys. In group 3, six renal arteries in five
      kidneys from groups 1 and 2 without RAS/RAR were analyzed as an internal control.
      RESULTS: Technical success (defined as increased vessel caliber after
      intervention) was achieved in 33 of the 34 revascularized arteries. A
      statistically significant increase in renal length occurred regardless of
      clinical outcome (pre-RAR, 9.5 cm; post-RAR, 10.5 cm; P < 0.0001). Parenchymal
      thickness and renal mass, however, improved only in patients who benefited
      clinically from RAR. Parenchymal enhancement was unchanged in any of the groups
      studied. No significant morphologic changes were detected in the control group.
      CONCLUSIONS: Magnetic resonance imaging and Gd-MRA detect anatomic and
      hemodynamic changes that occur with renal revascularization.

PMID- 9766053
TI  - Contrast-enhanced three-dimensional magnetic resonance angiography of the
      splanchnic vasculature before and after caloric stimulation. Original
      investigation.
AB  - RATIONALE AND OBJECTIVES: To develop a comprehensive noninvasive magnetic
      resonance angiography (MRA) strategy for the morphologic and functional
      assessment of the splanchnic arteries, based on a combination of breath-held
      contrast-enhanced 3D MRA and segmented k-space 2D phase-contrast acquisitions
      acquired before and after caloric stimulation. METHODS: Ten healthy volunteers
      were examined twice: once in the fasting state (6 hours with no food intake) and
      a second time following caloric stimulation with a standard 475-kcal meal. Flow
      in the superior mesenteric artery (SMA) and vein (SMV) was quantitated using a 2D
      breath-held, segmented k-space phase-contrast (PC) acquisition in a plane
      perpendicular to the axis of the vessels, while vascular morphology was displayed
      with a contrast-enhanced 3D MRA acquisition consisting of 44 contiguous 2-mm
      sections, acquired in apnea (28 seconds). For comparative analysis, the
      splanchnic vasculature was divided into 11 segments and evaluated on a 2-point
      scale (cannot exclude pathology, can exclude pathology). RESULTS: Flow volume in
      the SMA increased from 2.3 ml/min/kg (+/- 0.9 ml/min kg) to 7.3 ml/min kg (+/-
      4.7 ml/min kg) following caloric stimulation (P < 0.05). Flow in the SMV exceeded
      flow in the SMA and increased from 3.4 ml/min/kg (+/- 0.3 ml/min kg) to 9.1
      ml/min/kg (+/- 4.8 ml/min/kg) following stimulation. Flow volume of SMV
      correlated better with SMA flow after stimulation. Caloric stimulation
      significantly improved visualization of the splanchnic arterial vasculature (P <
      0.05). Only 5 of 110 evaluated arterial segments (4.5%) remained inadequately
      seen to exclude vascular pathology. CONCLUSION: Magnetic resonance imaging offers
      a comprehensive assessment of the splanchnic arterial vasculature based on 3D
      display of vessel morphology and analysis of flow function. While the most
      relevant proximal vessel segments are visible even under fasting conditions,
      caloric stimulation enhances visualization of small vessels.

PMID- 9766052
TI  - Magnetic resonance angiography of mesenteric arteries. A review.
AB  - There has been continued development of MRI techniques for evaluating mesenteric
      vascular disease. Contrast-enhanced magnetic resonance angiography (MRA) can
      provide reproducible high resolution, high contrast images of the arterial and
      venous mesenteric vasculature and may allow detection of segmental ischemia by
      detection of segmental delayed mesenteric or bowel wall enhancement. Cine phase
      contrast MRA can provide additional information about the rate and volume of flow
      within the major mesenteric arteries and veins. Real-time MRI can provide
      interactive visualization of the mesenteric vessels in any plane, and with
      suitable bowel contrast, it can be used to monitor global and segmental small
      bowel motility. With in vivo MR oximetry, flow independent measurements of the T2
      relaxation of blood allow the oxygen saturation of the mesenteric circulation to
      be determined. These MR techniques can be combined for evaluating both anatomic
      and functional aspects of the mesenteric circulation.

PMID- 9766054
TI  - Magnetic resonance angiography of the hand. A review.

PMID- 9766055
TI  - Magnetic resonance angiography with gadomer-17. An animal study original
      investigation.
AB  - RATIONALE AND OBJECTIVES: Our purpose was to investigate a "blood pool" contrast
      agent for abdominal and thoracic MR angiography by comparison with standard ionic
      and nonionic gadolinium-based contrast agents, which redistribute into the
      extracellular fluid compartment. METHODS: Abdominal and thoracic MR angiography
      was performed in three adult dogs using a three-dimensional spoiled gradient echo
      pulse sequence before and after intravenous administration of one of three
      gadolinium-based contrast agents (gadopentetate dimeglumine, gadobutrol, and
      gadomer-17). Each compound was tested at five different doses in all three dogs.
      Quantitative analysis of signal-to-noise ratio (SNR) was performed in the aorta,
      inferior vena cava (IVC), liver, spleen, kidney (medulla and cortex), fat, and
      muscle. RESULTS: Gadomer-17 improved visualization of vascular anatomy at doses
      of 0.025, 0.05, 0.1, and 0.2 mmol/kg with three-fold greater aorta SNR during the
      arterial phase and more than four-fold greater aorta and IVC SNR during the
      equilibrium phase, in comparison with gadopentetate dimeglumine and gadobutrol at
      equal doses. CONCLUSIONS: Gadomer-17 is a promising contrast agent for both
      arterial phase and equilibrium phase MR angiography.

PMID- 9766056
TI  - The future of contrast-enhanced magnetic resonance angiography. Are blood pool
      agents needed?

PMID- 9766057
TI  - An improved direct plate method for the enumeration of stressed Escherichia coli
      O157:H7 from food.
AB  - The use of sorbitol MacConkey agar (SMAC) performed poorly in supporting growth
      of stressed Escherichia coli O157:H7 cells. Up to a 3-log difference was observed
      between counts on SMAC and tryptone soy agar (TSA). It is critical in the risk
      assessment of certain foods to be able to enumerate stressed and healthy E. coli
      O157:H7 in a background of potentially healthy competing bacteria. Investigations
      carried out to overcome the inhibitory effect of SMAC included the reduction of
      the selective agent concentration, inclusion of a recovery stage in broth prior
      to plating out, addition of recovery agents, and delayed exposure to the
      selective agent. The only successful approach was delayed exposure to the
      selective agent. This was achieved by resuscitating the stressed cells on a
      membrane placed on the surface of a TSA plate and, after a defined time period
      sufficient for full resuscitation, transferring the membrane to the surface of a
      SMAC plate. The choice of membrane material was critical for maintaining the
      positive sorbitol color change used to identify wild-type E. coli. Track-etched
      polycarbonate membranes allowed the typical color reactions to be visualized,
      whereas cellulose acetate did not. The method was validated with E. coli O157:H7
      cells stressed by low pH and high salt conditions, whereby all cells that would
      previously be undetectable on direct inoculation of SMAC were countable.

PMID- 9766058
TI  - Effectiveness of salt, pH, and diacetyl as inhibitors for Escherichia coli
      O157:H7 in dairy foods stored at refrigeration temperatures.
AB  - The behavior of Escherichia coli O157:H7 inoculated in 10% rehydrated nonfat dry
      milk adjusted to pH levels between 3.8 and 5.4 with lactic acid, salt levels of 0
      to 6%, and diacetyl levels of 0, 5, and 10 micrograms/g was determined at 4 and
      12 degrees C. Cell populations were determined by surface plating on tryptic soy
      agar after 7 and 35 days of incubation. Survival was also determined using retail
      cultured diary products. E. coli O157:H7 did not survive in skim milk at pH 3.8
      and was reduced by 3 log cycles at pH 4.1, regardless of salt, diacetyl, and
      temperature levels. At pH levels above 4.4, survival was observed at lower salt
      concentrations for up to 35 days at both 12 and 4 degrees C. The organism grew
      (up to a 2.2-log increase) at pH 5.0 at 2% salt levels after 35 days of storage
      at 12 degrees C. Diacetyl at a concentration of 10 ppm had no effect on survival
      and growth. In all but one case, E. coli O157:H7 was inactivated in yogurt, sour
      cream, and buttermilk at a rate similar to or greater than what was consistent
      with the acidified skim milk data. Also consistent with the skim milk data,
      growth occurred in two of the three cottage cheese samples at 12 degrees C after
      7 days but not after 35 days or at 4 degrees C, when a 1- to 2-log decline was
      observed.

PMID- 9766059
TI  - Bacterial cross-contamination of meat during liquid nitrogen immersion freezing.
AB  - Prerigor beef carcass surface tissue (BCT) was used to simulate lamb carcasses on
      a processing line with a 15-min liquid nitrogen (LN) immersion freezing step, and
      the potential for the dissemination of bacteria during freezing was examined.
      Streptomycin-resistant strains of Listeria innocua and Escherichia coli O157:H7
      spiked into a fecal slurry were inoculated onto BCT pieces that were introduced
      into the freezing process to represent contaminated carcasses. Following this
      introduction, subsequently frozen uninoculated BCT, LN, and LN containers were
      examined for the inoculated organisms. In the first study, BCT samples were
      inoculated with ca. 7 log CFU/cm2 of both L. innocua and E. coli O157:H7, spray
      washed with water and frozen, distributed among uninoculated BCT, in LN for 15
      min. In two separate trials, L. innocua was recovered by enrichment from all
      uninoculated BCT and LN samples. E. coli O157:H7 was also recovered from
      uninoculated BCT and LN, but this cross-contamination was more sporadic. Both
      species were recovered from the LN container following freezing. Attempts to
      enumerate cross-contaminating bacteria in the second trial indicated that
      contaminating levels were low (< 1.0 CFU/cm2 BCT). In a second study, a 2.0%
      lactic acid spray wash was used to reduce further the numbers of L. innocua
      introduced into the freezing system and resulted in fewer positive samples,
      although this organism was still recovered from many uninoculated BCT samples.
      When either bacterium was inoculated at lower initial levels (1.35 to 1.77 log
      CFU/cm2) and BCT was water or 2.0% lactic acid spray washed prior to freezing,
      neither L. innocua nor E. coli O157:H7 was recoverable by enrichment from
      uninoculated BCT, LN, or from the freezing container. Results demonstrate that
      bacterial cross-contamination of meat during LN immersion freezing can occur but
      indicate that the use of good sanitation practices and product with low microbial
      numbers can limit this occurrence.

PMID- 9766060
TI  - Bacterial profile of ground beef made from carcass tissue experimentally
      contaminated with pathogenic and spoilage bacteria before being washed with hot
      water, alkaline solution, or organic acid and then stored at 4 or 12 degrees C.
AB  - The long-term effectiveness of several beef-carcass surface-tissue (BCT) wash
      interventions on the microbiology of ground beef produced from this tissue was
      determined. BCT was inoculated with bovine feces containing one of two different
      levels (ca. 4 or 6 log CFU/ml) of Escherichia coli O157:H7, Listeria innocua,
      Salmonella typhimurium, and Clostridium sporogenes. The BCT was then subjected to
      one of several treatment washes: 2% (vol/vol) DL-lactic acid (LA), 2% (vol/vol)
      acetic acid (AA), 12% (wt/vol) trisodium phosphate (TSP), hot water (HW; 74 +/- 2
      degrees C at the tissue surface), or water (WW; 32 +/- 2 degrees C at the tissue
      surface). A control group was left untreated. After treatments, BCT was held at 4
      degrees C for 24 h and then ground. The ground beef was packaged and incubated at
      4 degrees C for 21 days or 12 degrees C for 3 days. AA-treated samples held at 12
      degrees C for 3 days yielded significantly lower aerobic plate counts than the
      control and also yielded the lowest levels of pseudomonads when compared to other
      sample groups. After being held at 4 degrees C for 21 days or 12 degrees C for 3
      days, samples treated with antimicrobial compounds had lower or no detectable (<
      1 CFU/g) levels of E. coli O157:H7, L. innocua, S. typhimurium, and C. sporogenes
      than beef treated with a WW or the control. Ground beef produced from tissue
      treated with HW yielded lower populations of these bacteria when compared to WW
      or untreated control beef, but the populations were generally higher than those
      observed in any of the antimicrobial chemical-treated samples. These trends
      continued throughout all storage conditions over time. Results from this study
      indicate that the use of carcass interventions, especially antimicrobial
      compounds, presently available to the slaughter industry will lower bacterial
      counts in ground beef.

PMID- 9766061
TI  - False-positive fluorescence by pink salmon tissue and staphylococci in a rapid
      test for Escherichia coli.
AB  - Fluorescence from 4-methylumbelliferyl-beta-D-glucuronide (MUG) hydrolysis is a
      common, rapid method for determining Escherichia coli in water and food. False
      positive fluorescence occurred when either pink salmon fillets were tested or
      beta-glucuronidase-positive Staphylococcus species were present in other fish
      products. Salmon fillet, E. coli, S. xylosus, and S. warneri produced 2, 17, 39,
      and 43 nmol of 4-methylumbelliferone per ml, respectively, in a one-step
      detection broth (lauryl salts tryptose broth with MUG) for E. coli after 48 h at
      35 degrees C. These false-positive reactions need to be considered when testing
      fish products, especially those contaminated through human handling.

PMID- 9766062
TI  - Antibacterial effects of N-sulfonated and N-sulfobenzoyl chitosan and application
      to oyster preservation.
AB  - The antibacterial effects of sulfonated and sulfobenzoyl chitosans were evaluated
      and compared with that of 69% deacetylated chitosan (DD69 chitosan). Minimal
      inhibitory concentrations of sulfonated chitosan (SC1, 0.63% sulfur content)
      against Shigella dysenteriae, Aeromonas hydrophila, Salmonella typhimurium, and
      Bacillus cereus were found to be lower than those of DD69 chitosan. A high sulfur
      content in sulfonated chitosan adversely influenced its antibacterial effect.
      Sulfobenzoyl chitosan (SBC) has excellent water solubility and an antibacterial
      effect comparable to that of SC1. SBC at 1,000 and 2,000 ppm extended the shelf
      life of oysters at 5 degrees C by 4 days at the former or by 7 days at least at
      the latter concentration. The growth of coliforms and Pseudomonas, Aeromonas, and
      Vibrio species on oysters was retarded by the addition of DD69 chitosan or SBC.

PMID- 9766063
TI  - Thawed cod fillets spoil less rapidly than unfrozen fillets when stored under
      modified atmosphere at 2 degrees C.
AB  - The effect of two months of frozen storage at -20 degrees C on the spoilage
      characteristics and shelf life of thawed and modified atmosphere packed (MAP) cod
      fillets stored at 2 degrees C was studied. Thawed MAP cod fillets were compared
      with fresh cod fillets stored in CO2-containing modified atmospheres with and
      without added oxygen. The shelf life of 11 to 12 days in the fresh MAP cod was
      extended to more than 20 days in the thawed MAP cod at 2 degrees C. This shelf
      life extension was most likely due to the inactivation of the spoilage bacterium
      Photobacterium phosphoreum during frozen storage as reflected both in chemical
      analyses and sensory evaluation. In contrast to fresh MAP cod fillets no
      significant production of trimethylamine occurred and almost no amine odor and
      taste were detected during 20 days of chill storage of thawed MAP cod fillets.
      The use of frozen fillets as raw material not only provides a more stable product
      in MAP but also allows much greater flexibility for production and distribution.
      However, a slightly increased concentration of dimethylamine, a larger drip loss,
      and detection of weak frozen storage flavor were observed in the thawed MAP cod
      fillets.

PMID- 9766064
TI  - Listeria innocua and Salmonella panama in mussels: a comparative study.
AB  - Bivalve molluscs are exposed to a wide range of contamination by pathogenic
      bacteria and viruses. Therefore, the behavior of bacterial pathogens in bivalves
      after harvesting is important in terms of food safety. Mussels were artificially
      contaminated with Listeria innocua and Salmonella panama, held under different
      conditions, and then examined for Listeria and Salmonella viable counts. In a
      simplified depuration system, L. innocua levels were lower than those observed
      for S. panama in mussels during the same period and under the same conditions.
      This result may be related to the rapid die-off reported for Listeria in
      seawater. In mussels stored in air, the two pathogens presented similar
      behaviors: levels of both pathogens remained constant in mussels during the
      storage period in air. However, in shucked mussels Listeria innocua counts
      increased with the duration of storage, whereas Salmonella panama showed a slight
      decrease.

PMID- 9766065
TI  - Alteration in sporulation, enterotoxin production, and protein synthesis by
      Clostridium perfringens type A following heat shock.
AB  - Application of a heat shock (43 to 50 degrees C) applied early during the
      sporulation process of Clostridium perfringens delayed spore and enterotoxin
      production. Final levels of heat-resistant spores were similar to the control,
      but enterotoxin levels were reduced when the heat shock was applied at the third
      hour of incubation. The response of the microorganism to the heat shock was also
      examined by analysis of pulse-labeled proteins. Seven heat shock proteins (HSPs)
      associated with vegetative cells were identified by polyacrylamide gel
      electrophoresis. Most were localized mainly in the membrane, although one small
      protein was mostly present in the cytoplasm. Fewer HSPs were detected during
      sporulation. Two HSPs were immunologically related to the GroEL and DnaK HSPs
      from Lactobacillus lactis and Escherichia coli, respectively.

PMID- 9766066
TI  - Microbiological quality and the inability of proteolytic Clostridium botulinum to
      produce toxin in film-packaged fresh-cut cabbage and lettuce.
AB  - The production of toxin by a 10-strain mixture of proteolytic Clostridium
      botulinum in fresh produce packaged in polyethylene films having high (7,000
      cc/m2/24 h; HOTR) and low (3,000 cc/m2/24 h; LOTR) relative oxygen permeability
      was determined. Shredded cabbage and lettuce inoculated with approximately 10(2)
      spores/g were placed in bags composed of the two films (1.4 kg/bag), and the bags
      were then vacuum sealed. Produce was stored at 4, 13, and 21 degrees C for up to
      21 (cabbage) or 28 (lettuce) days and analyzed periodically. At each sampling
      time, the gas composition within the bags, pH of the produce, and microbial
      populations (total aerobic and anaerobic microorganisms, lactic acid bacteria,
      psychrotrophic bacteria, and yeasts and molds) were determined. In addition, the
      presence of botulinal toxin was determined using the standard U.S. Food and Drug
      Administration mouse bioassay protocol. Bags made of HOTR film prolonged sensory
      quality of cabbage and lettuce, especially at 13 and 4 degrees C. Packaging
      material had an effect on the growth of various groups of microorganisms;
      however, there was not a general trend. For example, lettuce packaged in HOTR
      bags had higher aerobic microbial populations than that packed in LOTR, but no
      significant difference (P < or = 0.05) was observed with cabbage. Growth of
      psychrotrophic bacteria was greater in vegetables packaged in HOTR film while
      growth of yeasts and molds was not affected by either packaging film. Most
      differences in microbial populations in produce packaged in LOTR and HOTR films
      were less than 1 log10 CFU/g. Botulinal toxin was not detected in cabbage or
      lettuce packaged in either film or stored under any test condition.

PMID- 9766067
TI  - Conservative prediction of time to Clostridium botulinum toxin formation for use
      with time-temperature indicators to ensure the safety of foods.
AB  - Integrating-type time-temperature indicators (TTIs) may be utilized to warn food
      processors and consumers about storage conditions that may have rendered a food
      potentially hazardous. As an example of how integrated TTIs could be manufactured
      to emulate an infinite set of time-temperature situations, a set of conditions
      which have supported C. botulinum growth and toxin production was compiled. The
      time-temperature curve representing conservative times required for toxin
      formation was constructed with data from literature relating to toxin formation
      as a function of temperature in any media or food product. This set of critical
      time-temperature data is fit by a conservative empirical relationship that can be
      used to predict combinations of incubation times and storage temperatures that
      represent a potential health risk from C. botulinum in foods. A TTI could be
      constructed to indicate deviation from such a given set of conditions to bring
      attention to foods that may have been exposed to potentially hazardous
      temperatures with respect to C. botulinum toxin formation.

PMID- 9766068
TI  - Quality of commercial shelf-stable soymilk products.
AB  - Four brands of shelf-stable soymilks (three lots each) were evaluated for their
      quality. All samples were tested for trypsin inhibitor activity, microbial load
      (coliforms, aerobic mesophiles, and psychrotrophs), solids content, pH, color,
      and viscosity. Storage stability at 5 degrees C of the opened original containers
      was evaluated by microbiological analyses. Physical properties were consistent
      among three lots of the same brand, but varied among brands. Trypsin inhibitor
      activity ranged from 3.43 to 10.35 mg/g dried soymilk. The pH values of the
      soymilks varied between 6.41 and 7.34. Viscosity was measured between 16.5 and
      26.4 mPa. Solids content varied considerably among soymilks, from 6.88 to 12.37%
      (wt/vol). Freshly opened commercial soymilk contained fewer than one
      microorganism per ml in all microbial counts. During storage at 5 degrees C,
      microbial counts increased sharply after 2 to 3 weeks. A single microorganism
      predominated in each stored sample. Shelf life (defined as the time during which
      aerobic mesophile counts remained below 10(6) CFU/ml) varied from 3 to 4 weeks.
      The appearance and pH of soymilks remained unchanged even after 4 weeks of
      storage. Five types of microorganisms were found in stored soymilk samples; none
      of them produced acid.

PMID- 9766069
TI  - A nondestructive leak detection method for flexible food packages using hydrogen
      as a tracer gas.
AB  - A nondestructive leak detection method developed at Technical Research Centre of
      Finland (VTT) was tested for both gas-flushed and vacuum flexible packages. In
      the method, a gas package containing 0.5 to 5.0% (vol/vol) hydrogen in nitrogen
      was positioned in a test chamber, a controlled vacuum was pulled in the chamber
      through a pipe connected to a hydrogen sensor, and leaking packages were detected
      by the sensor as increased H2 concentration. The H2 tracer gas (0.5 to 5.0%) was
      introduced into leaking finished vacuum packages at 200 kPa pressure. Within 1 to
      4 s the developed test method was able to detect leaks down to 10 to 15 microns
      and 20 to 30 microns in diameter in commercially manufactured gas-flushed
      packages filled with roasted meat balls and vacuum packages filled with ground
      coffee, respectively. Before leak testing, the vacuum packages were charged with
      H2 for 30 s. The sensitivity and leak detection time of the test method were
      improved when the H2 concentration in the package was increased and when the free
      space in the test chamber was decreased. The evaluated H2 concentrations did not
      affect the sensory or microbiological quality of the roasted meat balls. This
      study clearly demonstrated that the hydrogen tracer gas leak detection method has
      potential to be further developed as a fast, nondestructive, on-line leak testing
      apparatus for flexible packages with or without a headspace.

PMID- 9766070
TI  - An evaluation of the collection and analysis of epidemiological data for support
      of food safety control systems.
AB  - Food-borne disease data collected by three U. K. environmental health departments
      were used in this study. The data were analyzed using a database designed to rank
      disease agents, food ingredients, and processing factors which contribute to
      cases of food-borne disease. The results established changes in patterns of food
      borne disease over time, pattern differences between U. K. localities and
      differences between areas of the United Kingdom and the United States. This type
      of analysis of epidemiological data provides scientific underpinning for hazard
      analysis critical control point systems for food safety control. The work
      highlights the need for a consistent procedure for collection of food-borne
      disease data and for a national database to facilitate analysis.

PMID- 9766071
TI  - College students' attitudes, practices, and knowledge of food safety.
AB  - A survey instrument was developed to assess attitudes, practices, and knowledge
      of food safety of college students in three U.S. geographic locations. Eight
      hundred twenty-four students in both food-related (one-third of sample) and
      nonfood-related disciplines completed the questionnaire during classroom periods.
      Data were analyzed to obtain total attitude, practice, and safety scores, with
      emphasis given to analyzing differences among disciplines and demographic
      characteristics. Mean scores were given for each of the survey items, and results
      from open-ended questions were discussed. Dietetic, food science, nutrition, and
      health majors had significantly (< or = 0.05) higher attitude scores than
      students majoring in other disciplines. No differences were found among
      disciplines for the practice scores, which ranged from 74 to 79% of the total
      possible practice score. Students enrolled in dietetics, arts and science
      (physical sciences), and veterinary medicine had significantly (< or = 0.05)
      higher knowledge scores, although the highest mean score (for dietetics) was only
      74% of the total possible score. Women who had enrolled in a college course that
      included food safety information had significantly (< or = 0.05) higher attitude
      and practice scores. Such course enrollment led to both genders having
      significantly (< or = 0.05) higher knowledge scores than those without this
      opportunity. Implications were given for using these data to encourage college
      professors in food-related disciplines to become involved with the education of
      all future consumers, especially as the prevalence of food safety controversies
      is likely to increase as the food supply changes and technology becomes more
      sophisticated.

PMID- 9766072
TI  - Survival of Escherichia coli O157:H7 after freezing and thawing in ground beef
      patties.
AB  - Survival of Escherichia coli O157:H7 strains QA 326, and ATCC 43889, 43894, and
      43895 after freezing (-20 degrees C, 24 h) and thawing (4 degrees C for 12 h, 23
      degrees C for 3 h, or microwave heating of 700 W for 120 s) in ground beef
      patties was determined by reference most probable number (MPN), hydrophobic grid
      membrane filter SD-39 agar, and sorbitol MacConkey agar (SMA) spread-plating
      methods. Populations decreased from 0.62 to 2.52 log10 CFU/g, with the extent
      varying significantly by strain. Strain QA 326 populations almost always
      decreased the most, up to 1.87 log10 CFU/g more than the least sensitive strain.
      Microwave heating was the most lethal thawing treatment for strain QA 326, and 4
      degrees C thawing was the most lethal treatment for strain ATCC 43894. Thawing
      treatments varied in relative lethality for the other two strains. For strain QA
      326 (4 degrees C and microwave thaw treatments) and strain ATCC 43889 (4 and 23
      degrees C thawing), the enumeration method significantly affected a population
      decrease. The SD-39 agar method best recovered strain QA 326 while the SD-39 agar
      method and the reference MPN method best recovered strain ATCC 43889 after 4 and
      23 degrees C thawing, respectively. The greatest difference in population
      decrease measured by any two methods was 0.58 log10 CFU/g. Results showed (i) a
      wide range in freeze-thaw sensitivity among E. coli O157:H7 strains, (ii) no
      thawing method had consistently and significantly greater lethality, and (iii)
      the reference MPN, SD-39 agar, and SMA methods differed little in ability to
      enumerate E. coli O157:H7.

PMID- 9766073
TI  - Thermotolerance of Escherichia coli O157:H7 ATCC 43,894, Escherichia coli B, and
      an rpoS-deficient mutant of Escherichia coli O157:H7 ATCC 43,895 following
      exposure to 1.5% acetic acid.
AB  - On a beef carcass, Escherichia coli may sequentially encounter acid- and heat
      intervention steps. This study tested whether acid stress (1.5% [vol/vol] acetic
      acid, pH 4.0, 37 degrees C, 15 min) would enhance subsequent heat resistance of
      E. coli. Initially, cells (E. coli O157:H7 ATCC 43894, nonpathogenic E. coli B
      [strain FRIK-124], and rpoS-deficient mutant 813-6 [derived from E. coli O157:H7
      ATCC 43895]) were acid stressed and transferred to 54 degrees C trypticase soy
      broth (TSB), and survivors were immediately enumerated after at least three
      intervals of 12, 2, and 6 min, respectively, by plating. The ATCC 43894 and 813-6
      strains survived the acid stress but strain FRIK-124 did not. Acid-stressed ATCC
      43894 had significantly lower D values than the non-acid-stressed controls.
      Strain 813-6 had significantly lower D values than strain ATCC 43894, with no
      significant difference between acid-stressed and non-acid-stressed cells. In a
      second experiment, cooling of cells prior to plating resulted in an increased D
      value for acid-stressed ATCC 43894 cells, such that it was not significantly
      different from the D value for non-acid-stressed controls. Using this protocol,
      there was no significant difference in D values between acid-stressed and non
      acid-stressed ATCC 43894 cells in prewarmed TSB (54, 58, and 62 degrees C), in
      prewarmed ground beef slurry (GBS; 58 degrees C), or in TSB and GBS inoculated at
      5 degrees C and heated to 58 degrees C. The acid stress tested does not enhance
      subsequent heat resistance of E. coli.

PMID- 9766074
TI  - Polymacron enzyme immunoassay system for detection of naturally contaminating
      Salmonella in foods, feeds, and environmental samples.
AB  - A simple dot blot enzyme immunoassay was developed to screen enrichment broth
      cultures for the presence of Salmonella. This unique system utilizes macroporous
      polyester cloth (Polymacron) with an inexpensive hemoglobin coating to provide a
      high-affinity adsorbent for lipopolysaccharide (LPS) antigens in test samples.
      Bound LPS antigens are then detected using a monoclonal antibody conjugate
      recognizing a core oligosaccharide epitope common to all salmonellae frequently
      found in foods and related samples. The entire test (not including enrichment
      culture) could be completed in less than 1 h. The performance of this assay was
      evaluated in the analysis of enrichment broth cultures from a variety of egg and
      dairy products, chicken carcasses, animal feeds, and food-processing plant
      environmental samples for the presence of Salmonella.

PMID- 9766075
TI  - Specific inhibition of Photobacterium phosphoreum extends the shelf life of
      modified-atmosphere-packed cod fillets.
AB  - Inhibition of the specific spoilage organism, Photobacterium phosphoreum, was
      studied in model substrates and in modified-atmosphere-packed cod fillets. The
      objective was to determine how inhibition of this organism influenced spoilage.
      The spoilage reactions limiting shelf life were studied rather than the
      development of a new product. In naturally contaminated modified-atmosphere
      packed cod fillets, 500 ppm Na2CaEDTA reduced the growth rate of P. phosphoreum
      by 40% and shelf life was increased proportionally by 40%, from 15 to 17 days to
      21 to 23 days at 0 degree C. In aerobically stored cod fillets other
      microorganisms were responsible for spoilage and Na2CaEDTA had no effect on shelf
      life. The extension of the shelf life of modified-atmosphere-packed cod therefore
      was a result of the reduced growth of P. phosphoreum and no other microbial or
      nonmicrobial spoilage reactions limited shelf life. These results confirmed P.
      phosphoreum as the specific spoilage organism in modified-atmosphere-packed cod
      and showed the organism to have an extensive spoilage domain. Consequently, any
      preservation procedure able to reduce growth of P. phosphoreum is likely to
      extend shelf life of packed cod. However, the effect of different inhibitory
      compounds in model systems as well as results from packed cod indicated the need
      to include product studies in the screening of antimicrobials and in the
      development of preservation procedures.

PMID- 9766076
TI  - Reactivities of genus-specific monoclonal antibody EM-6E11 against Listeria
      species and serotypes of Listeria monocytogenes grown in nonselective and
      selective enrichment broth media.
AB  - Depending on the growth medium used for enrichment of bacterial cells prior to
      assay, the monoclonal antibody (MAb) EM-6E11 recognizing Listeria genus-specific
      epitope on 43 and 94 to 97 kDa cell-surface antigens (A. K. Bhunia and M. G.
      Johnson, Appl. Environ. Microbiol. 58:1924-1929, 1992) exhibited extensive
      variability in the detection of Listeria species. MAb EM-6E11 strongly detected
      live cells of all Listeria species and all serotypes of L. monocytogenes by ELISA
      when cells were grown in nonselective brain heart infusion (BHI) broth, in
      selective Listeria enrichment broth (LEB), or in Listeria repair broth (LRB). In
      contrast, EM-6E11 detected only four of the thirteen serotypes of L.
      monocytogenes (serotypes 1/2c, 3b, 4ab, and 7) when cells were grown in the UVM1
      formulation of Listeria enrichment broth (UVM1) or Fraser broth (FRB). This MAb
      failed to react with live cells of four other Listeria species, including L.
      ivanovii, L. welshimeri, L. grayi, and L. murrayi cells grown in UVM1 or FRB.
      Heating of Listeria cells at 100 degrees C for 20 min, irrespective of the
      enrichment media used, led to large losses of MAb EM-6E11 reactivity in ELISA,
      suggesting that the specific cell-surface epitopes involved may not be heat
      stable. Our results confirm that MAb EM-6E11 is suitable for detection of live
      cells but not heat-killed cells of Listeria spp. and can be used in conjunction
      with an enrichment step in BHI, LEB, or LRB but not in UVM1 or FRB.

PMID- 9766077
TI  - Identification of Listeria monocytogenes from unpasteurized apple juice using
      rapid test kits.
AB  - A microbiological survey of 50 retail juices was conducted in the fall of 1996.
      These juices were analyzed for Listeria monocytogenes, Escherichia coli O157:H7,
      Salmonella, coliforms, fecal coliforms, and pH. Two unpasteurized juices were
      positive for L. monocytogenes: an apple juice and an apple raspberry blend with a
      pH of 3.78 and 3.75, respectively. Three L. monocytogenes isolates were
      characterized. The colonies were typical for Listeria sp. on Oxford and lithium
      chloride-phenylethanol-moxalactam agars and were beta-hemolytic on sheep blood
      agar. The isolates required 5 days of incubation at 35 degrees C to produce a
      positive rhamnose reaction in a phenol red carbohydrate broth. This slow rhamnose
      utilization resulted in these isolates not being identified using the Micro-ID
      test strip (Organon Technika). However, the isolates were positive for L.
      monocytogenes using the API Listeria strip (BioMerieux) and a multiplex
      polymerase chain reaction for detection of the hemolysis (hyla) and invasion
      associated protein (iap) genes.

PMID- 9766078
TI  - Inactivation of Listeria monocytogenes in milk by pulsed electric field.
AB  - Pasteurized whole, 2%, and skim milk were inoculated with Listeria monocytogenes
      Scott A and treated with high-voltage pulsed electric field (PEF). The effects of
      milk composition (fat content) and PEF parameters (electric field strength,
      treatment time, and treatment temperature) on the inactivation of the bacterium
      were studied. No significant differences were observed in the inactivation of L.
      monocytogenes Scott A in three types of milk by PEF treatment. With treatment at
      25 degrees C, 1- to 3-log reductions of L. monocytogenes were observed. PEF
      lethal effect was a function of field strength and treatment time. Higher field
      strength or longer treatment time resulted in a greater reduction of viable
      cells. A 4-log reduction of the bacterium was obtained by increasing the
      treatment temperature to 50 degrees C. Results indicate that the use of a high
      voltage PEF is a promising technology for inactivation of foodborne pathogens.

PMID- 9766079
TI  - Occurrence of Erysipelothrix spp. in chicken meat parts from a processing plant.
AB  - From March 1996 to March 1997, 153 domestic raw chicken meat samples, including
      71 thigh, 50 outer breast muscle, and 32 white meat samples, from a processing
      plant located in a chicken abattoir in Nagano Prefecture, Japan, were examined
      for the presence of Erysipelothrix spp. Erysipelothrix spp. were isolated from 49
      (30.0%) of the 153 chicken meat samples. Of 67 Erysipelothrix isolates, 65 and 2
      isolates were identified as E rhusiopathiae and E. tonsillarum. E. rhusiopathiae
      and E. tonsillarum isolates were serotyped into 11 and 2 different serovars,
      respectively. These findings might indicate that domestic chicken meat is
      frequently contaminated with E. rhusiopathiae and seems to be a potential source
      of human Erysipelothrix infection.

PMID- 9766081
TI  - Oscillatory high hydrostatic pressure inactivation of Zygosaccharomyces bailii.
AB  - Zygosaccharomyces bailii inactivation was evaluated in oscillatory high
      hydrostatic pressure (HHP) treatments at sublethal pressures (207, 241, or 276
      MPa) and compared with continuous HHP treatments in laboratory model systems with
      a water activity (aw) of 0.98 and pH 3.5. The yeast was inoculated into
      laboratory model systems and subjected to HHP in sterile bags. Two HHP treatments
      were conducted: continuous (holding times of 5, 10, 15, 20, 30, 60, or 90 min)
      and oscillatory (two, three, or four cycles with holding times of 5 min and two
      cycles with holding times of 10 min). Oscillatory pressure treatments increased
      the effectiveness of HHP processing. For equal holding times, Z. bailii counts
      decreased as the number of cycles increased. Holding times of 20 min in HHP
      oscillatory treatments at 276 MPa assured inactivation (< 10 CFU/ml) of Z. bailii
      initial inoculum. Oscillatory pressurization could be useful to decrease Z.
      bailii inactivation time.

PMID- 9766080
TI  - Interactions between pairs of bacteriocins from lactic bacteria.
AB  - Activity of pairs of crude extracts of lactic acid bacteria (LAB) containing
      different bacteriocins (nisin, pediocin AcH, lacticin 481, lactacin F, and
      lactacin B) was measured against 10 different indicator strains. Experiments were
      carried out both in liquid and on solid media. Both synergisms and antagonisms
      were observed. Lacticin 481 produced mainly antagonistic effects whereas pediocin
      AcH produced mainly synergistic effects. The use of more than one LAB bacteriocin
      as a combination biopreservative might be envisaged.

PMID- 9766082
TI  - A general framework illustrating an approach to quantitative microbial food
      safety risk assessment.
AB  - Hazard analysis critical control point (HACCP), risk assessment, predictive
      microbiology, and dose-response modeling have been recognized as important tools
      for the assessment and management of health risks posed by food-borne pathogens.
      Unfortunately, the biology of both the food chain and food poisoning is complex
      and dynamic. Therefore, mathematical modeling of microbial risk from food
      production through to consumption and illness is difficult. Nevertheless,
      previous authors have made impressive progress in modeling specific pathogen-food
      consumer combinations. In this study a framework for a Monte Carlo model of a
      generic food system was developed. It links together food ingredients, batch
      processing, cross contamination, microbial growth, cooking, recontamination,
      consumption, human exposure to pathogens, the dose-response relationship, and the
      biologic and economic impact components of such risks. This framework is
      presented to illustrate one potential approach to quantitative risk assessment
      for microbial food safety. It requires refinement with appropriate distributions
      and mathematical relationships before it can be applied to a specific pathogen
      food-consumer situation.

PMID- 9766083
TI  - Foodborne illness in the elderly.
AB  - The elderly (> or = 65 years of age) are more susceptible to morbidity and
      mortality from foodborne-induced gastroenteritis than younger individuals.
      Several factors contribute to the increased susceptibility to foodborne
      infections as well as other infections in elderly populations. These include an
      age-associated decrease in humoral and cellular immunity, age-related changes in
      the gastrointestinal tract (decreased production of gastric acid and decreased
      intestinal motility), malnutrition, lack of exercise, entry into nursing homes,
      and excessive use of antibiotics. Data from foodborne outbreaks associated with
      nursing homes indicate that the elderly are more likely to die from foodborne
      Campylobacter, Clostridium perfringens, Escherichia coli O157:H7, Salmonella, and
      Staphylococcus aureus infections than the general population. Infections by
      Salmonella species are the most common cause of illness and death in nursing
      homes with Salmonella enteritidis as the major cause of both morbidity and
      mortality. While it is impossible to turn back the clock, practicing a healthy
      life-style with regular exercise, maintaining a balanced diet, receiving regular
      health care, paying attention to personal hygiene, and monitoring food
      preparation and handling should lead to a reduced incidence of foodborne and
      other infections in the elderly.

PMID- 9766084
TI  - Arsenic speciation in manufactured seafood products.
AB  - The literature on the speciation of arsenic (As) in seafoods was critically
      reviewed. Most research has been directed toward fresh seafood products with few
      papers dealing with As speciation in manufactured seafoods. Predictions
      concerning As species made on the basis of fresh seafood products cannot be
      extrapolated to manufactured seafoods. Therefore, due to the numerous species of
      As, the scarcity of data concerning their presence in foods, the transformations
      each species may undergo during industrial processing and cooking, and the lack
      of legislation on permitted As levels in seafood products, As species in
      manufactured seafood products need to be determined and quantified.

PMID- 9766085
TI  - Hazard analysis and critical control point principles and application guidelines.
      Adopted August 14, 1997. National Advisory Committee on Microbiological Criteria
      for Foods.
AB  - The HACCP Subcommittee of the National Advisory Committee on Microbiological
      Criteria for Foods (NACMCF) has prepared a revision of the document "Hazard
      Analysis and Critical Control Point System" that was adopted by the Committee in
      1992. The Committee retained the previous seven HACCP principles but made their
      wording more concise; revised and added definitions such as those for hazard,
      verification, and validation; included new sections on prerequisite programs,
      education and training, and implementation and maintenance of the HACCP plan;
      revised and provided a more detailed explanation of the application of HACCP
      principles, especially hazard analysis and verification; and added or revised
      Appendices such as new examples of prerequisite programs and an additional
      decision tree for identifying critical control points (CCPs).

PMID- 9766086
TI  - [Aortoiliac graft infection as a diagnostic and treatment problem].
AB  - Aortoiliac graft infection occurs in 2-6% of patients with such prosthesis. This
      condition is seldom properly diagnosed by conventional radiographic methods,
      leading to high morbidity and mortality. Clinically, the diagnosis of aortic
      graft infection is difficult because patients may have a variety of nondescript
      clinical complaints. The diagnosis of graft infection when associated with
      minimal or absent clinical signs of low-grade infection is uncertain, but is
      critically important to avoid frequently catastrophic complications such as
      sepsis, gastrointestinal hemorrhage, and suture line disruption. AIM OF THE
      STUDY: identification of bacterial flora present in aortoiliac graft infection;
      the presentation of my own experience in the detection of aortoiliac graft
      infection with special description of isotopic study with WBC labeled 99mTc HM
      PAO and estimation of the usefulness of this test in comparison with computed
      tomography, ultrasonography, fistulography and angiography; evaluation of the
      usefulness of various treatment methods; establishing principles (algorithm) of
      diagnostic and therapeutic procedures in the case of the suspicion of aortoiliac
      graft infection. As many as 1190 patients with implanted aortoiliac graft in 1986
      1996 at the General and Vascular Surgery Clinic in Szczecin were studied (Tab.
      2). Thirty-one patients in the study had deep aortoiliac graft infection (Tab.
      3), while 9 patients had, in addition, prosthetic-enteric fistulae and 1 had
      arterio-enteric secondary fistulae. The group of 31 patients with deep graft
      infection, that is 2.6% of all patients (1190), had aortoiliac graft implanted at
      the mentioned time period (Tab. 4, 5). Test results for detection of graft
      infection have been analysed (Tab. 17). The results of isotopic investigation
      (Tab. 16), computed tomography (Tab. 11), ultrasonography (Tab. 13),
      fistulography (Tab. 14) and angiography (Tab. 15) were compared with
      intraoperative state or in a case of exclusion of infection, with results of
      follow up. Results of various paths of treatment were estimated (Tab. 18). Based
      on performed cultures most common bacterial flora from infected grafts, was
      identified (Tab. 9, 10). The sensitivity of the isotopic study with labeled white
      blood cells in detection of graft infection was 88%, specificity was 97%,
      accuracy 93%, positive predictive value 96%. Other useful diagnostic procedures
      in detection of aortic graft infection are: computed tomography with an accuracy
      of 75%, endoscopic investigation useful in detection of arterio-enteric fistulae
      with an accuracy of 50% and ultrasonography with an accuracy of 35.5% (Tab. 17).
      The choice of the best treatment is still controversial. In my material total
      excision of infected graft and extraanatomic revascularization were burdened with
      50% mortality rate. Among patients treated less radically the mortality rate was
      considerably lower. In a group of patients with the excision of the infected
      graft only, the mortality rate was 9% but the amputation rate was 36.4% and in a
      group of patients with excision of infected graft and reconstruction in situ, the
      mortality rate was 25% (Tab. 18). Taking into consideration our results, less
      aggressive methods of aortic graft infection treatment such as the excision of
      the infected part of the prosthesis with or without in situ revascularization if
      only possible should be recommended. Most common in bacterial cultures from
      infected aortoiliac grafts with prosthetic-enteric fistulae were Escherichia coli
      found (Tab. 10). In infections without fistula various types of Staphylococcus
      aureus were identified (Tab. 9). CONCLUSIONS: 1. In cases of aortoiliac graft
      infection the most common cultured bacteria are found to be Staphylococcus
      aureus. If there is additional prosthetic-enteric fistula Escherichia coli is the
      most common cultured bacteria. 2. In a case there was suspicion of aortoiliac
      graft infection, proper diagnostic procedures are most important for effective ma

PMID- 9766087
TI  - An invitation to join in difficulty: realizing the deeper promise of group
      psychotherapy.
AB  - Group psychotherapy has proven effective in treating an impressive array of
      specific problems. Clinical experience has also shown its utility in alleviating
      the more general, and very costly, alienation and pain with which the human
      condition is often fraught. Recent changes in health care delivery reflect a
      marketplace that emphasizes cost containment, brevity and specificity of
      treatment, and a narrowed focus of training. Techniques are often valued above
      relationships. In this climate, we are in danger of losing sight of group
      therapy's deeper promise; the experiential lesson that human beings must move
      toward each other with involvement and a commitment to understanding in response
      to the inevitable difficulties that arise as we share time, space, and resources.

PMID- 9766088
TI  - Course design: an integration of didactic and experiential approaches to graduate
      training of group therapy.
AB  - Graduate training programs attempt to teach group therapy courses using
      experiential learning methods and theoretical concepts. Presently, however, these
      courses often maintain a rather unstructured format for fostering an experiential
      group process. The literature suggests that without standardized course
      objectives, students are vulnerable to harm and inadequately prepared for
      professional demands, and faculty are insufficiently prepared with guidelines for
      instruction. This article reviews the historical evolution of experiential
      courses, raises questions about the ethical integrity of such courses in their
      current form, and proposes a new course design that integrates essential
      components of learning theory. Standards for integrating a developmental approach
      to learning, beginning with didactic tasks and advancing to more experiential
      tasks, more effectively uphold ethical principles, provide an outline for
      comprehensive instruction, and enhance student learning.

PMID- 9766089
TI  - Psychodynamic-supportive group therapy model for elderly Holocaust survivors.
AB  - The physical and mental consequences of the Holocaust combined with difficult
      present events and the problems of old age can have devastating effects on
      survivors. Our clinic has recently introduced a psychodynamic-supportive group
      therapy model for elderly Holocaust survivors. The model includes specific
      integrative interventions, which are based on Horowitz's model of mourning and
      coping with stress and the leaders' clinical experience. The aim of the group is
      to improve the patients' homeostasis and enhance their ego functions and
      adaptation to inner and outer worlds. The theory and working model are described.

PMID- 9766090
TI  - A relational approach to group therapy for women with bulimia nervosa: moving
      from understanding to action.
AB  - This article explains how the psychology of women can inform group treatment by
      translating relational theory (RT) into practice within a short-term outpatient
      bulimia group. First, the article provides a brief overview of a relational
      understanding of women's psychological development, the etiology and maintenance
      of bulimia nervosa, and group psychotherapy. Then, clinical vignettes illustrate
      the application of RT in practice through discussion of four main healing factors
      at work in the different stages of the group. Through promoting validation, self
      empathy, mutuality, and empowerment, the leader helps group members identify and
      change relational patterns that have kept them connected with food and
      disconnected from themselves and others. The goal of treatment is to help members
      move toward mutually empathic and empowering relationships inside and outside the
      group.

PMID- 9766091
TI  - The advanced-stage therapy group.
AB  - Many authors describe a stage of maturity in the development of groups, but each
      highlights a different dimension. This article describes the characteristics of
      the advanced stage and the main axes along which it develops (internalization and
      containment, symbolization, self and self-other development, differentiation and
      individuation). It also offers a conceptual explanation for these developments
      and attempts to identify the conditions necessary for the emergence of this stage
      of maturity. An understanding of this stage and the conditions required for its
      development can be used by the group leader as a compass to help him or her
      navigate the group toward this objective.

PMID- 9766092
TI  - Envy in the group-therapy process.
AB  - The origins and vicissitudes of envy are discussed from the viewpoints of Boris
      and the Kleinians. Their ideas, coupled with a relational perspective of the
      therapeutic process, enrich our understanding and inform our work concerning the
      emergence, processing, and working through of envy in the therapy group. A
      variable in the negative therapeutic reaction, envy can be destructive to the
      therapy process. It is proposed that envy, accompanied by shame and guilt, is
      likely to enter the group via enactments. They are fueled by projective
      identification, which, if ignored, impede the continuation of the group process.
      Four clinical vignettes illustrate how envy enters the group and how the group
      functions as a container and transformational object as it processes the
      projective identifications and works through the enactments.

PMID- 9766093
TI  - Group psychotherapy for women molested in childhood: psychological and somatic
      symptoms and medical visits.
AB  - Molested women who completed a series of 16 weekly group psychotherapy sessions
      conducted by social workers improved substantially regarding various aspects of
      psychological functioning, including self-image, coping techniques, relationship
      issues, and mothering. In addition, there was significant improvement in all
      psychological symptom scales and all global indices of symptomatic distress
      measured by the SCL-90-R. Furthermore, the improvement was present immediately
      after therapy and, with the exception of the hostility score, persisted 1 year
      later. Although the somatization score was reduced, the number of visits for
      physical symptoms did not change. The patients studied manifested characteristics
      typical of previously surveyed women with a history of childhood abuse, including
      a frequent history of major surgery (Drossman et al., 1996; Longstreth & Wolde
      Tsadik, 1993; Springs & Friedrich, 1992) and, in some, a previous problem with
      alcohol (Springs & Friedrich, 1992; Walker et al., 1995) or drugs (Longstreth &
      Wolde-Tsadik, 1993; Miller & McCluskey-Fawcett, 1993; Springs & Friedrich, 1992).
      Also, nearly one half of the subjects had irritable bowel syndrome, the
      prototypical functional bowel disorder (Drossman et al., 1995; Longstreth & Wolde
      Tsadik, 1993; Scarinci et al., 1994; Walker et al., 1995). Most of their baseline
      SCL-90-R scores were > 1 SD above the nonpatient norms. A problem inherent in
      assessing the long-term benefit of this study and other group psychotherapy
      studies is the tendency for some patients to continue similar or different forms
      of therapy after completing the group sessions. More than one half of patients
      received subsequent therapy that could have influenced their status at 1-year
      follow-up. However, most of the symptom dimensions and all global indices were
      similar 1 year posttherapy in the women who did not receive more treatment as
      compared to results in the women who did. Patients who received additional
      therapy had higher somatization scores before, immediately after, and 1 year
      posttherapy; scores in the other group increased 1 year posttherapy. Although the
      indications for subsequent therapy were not surveyed, there was an association
      between additional psychological care seeking and somatization. Furthermore,
      improvement in psychological status reflected by the phobic-anxiety score
      immediately posttherapy may have contributed to the decision of some patients to
      seek subsequent therapy. In the group without additional treatment, the loss of
      some of the initial somatization improvement at 1 year may have contributed to
      the lack of reduction in medical care visits in the combined groups. We speculate
      that provision of additional therapy to more patients might have had a long-term
      effect on somatization and reduced medical visits. We obtained complete
      psychological data and nearly complete medical-visit data on our patients, and
      our survey included 1-year follow-up. Our survey did not meet rigorous
      methodological standards for an outcome study, however. We surveyed only a small
      number of patients and did not collect similar data on an untreated control
      group. It was not possible to distinguish health care visits for organic versus
      functional disorders, but such a distinction may be artificial, because
      psychological factors may influence health care seeking for "organic" illness.
      Because our measurements came from a subset of our patients who were willing to
      complete the survey questionnaires, we do not know how generalizable the findings
      are. There is increasing awareness among health care professionals that childhood
      sexual abuse is common and that it may have serious and long-term psychological
      and medical sequelae. Our data suggest that group psychotherapy by social workers
      for women victims may have long-lasting psychological and somatic symptom
      benefits. Reduction in health care usage was not found, and this outcome may
      require the identification and treatment of patients who need additi

PMID- 9766094
TI  - [Artemisia annua for the treatment of malaria].

PMID- 9766095
TI  - Xenoestrogens, pollution & health: a critical review.
AB  - This review article provides basic information concerning the xenoestrogens (i.e.
      the sexual hormone mimetic or disruptive compounds) in a perspective willingly
      selective of the recent literature. In the second part, a hypothetical link
      between xenoestrogens and disturbances of the central nervous system is
      considered with respect to steroids more directly involved in the CNS, i.e. the
      neurosteroids. The data accumulated so far on xenoestrogens present in the
      environment and their possible competition for membrane-bound neurosteroid
      receptor sites lend support to the working hypothesis that human behaviour could
      be affected in the daily life by exposure to chemical pollutants.

PMID- 9766096
TI  - [Reactions and interactions of drugs].

PMID- 9766097
TI  - 'Public health malpractice, plain and simple'.

PMID- 9766098
TI  - NIDR and other factors.

PMID- 9766099
TI  - Invading the oral cavity.

PMID- 9766100
TI  - About diamond burs.

PMID- 9766101
TI  - Insurance standards.

PMID- 9766102
TI  - Stress causes slow healing.

PMID- 9766103
TI  - At what age do you hope to be able to hang up your high-speed handpiece and
      retire?

PMID- 9766104
TI  - Sociodemographic distribution of pediatric dental caries: NHANES III, 1988-1994.
AB  - This article examines the extent to which caries prevalence and untreated caries
      vary in children by ethnicity and household income level. Data from the Third
      National Health and Nutrition Examination Survey, 1988-1994, for 10,332 children
      2 to 18 years of age indicate that lower-income children and Mexican-American and
      African-American children are more likely to have a higher prevalence of caries
      and more unmet treatment needs than their higher-income and non-Hispanic white
      counterparts.

PMID- 9766105
TI  - Aerosol and splatter contamination from the operative site during ultrasonic
      scaling.
AB  - As concern about indoor air quality increases, attention is being placed on the
      aerosol and splatter produced during dental procedures. This study quantifies the
      contamination produced by ultrasonic scalers during in vitro scaling without
      coolant water. When compared with the handheld curette used as a control, all
      ultrasonic scalers and tips tested produced significant aerosol and splatter
      regardless of the type of scaler, the power level or the insert. The ADA
      recommended method for controlling contaminated aerosol and splatter is the use
      of a large-bore high-volume evacuator. This study supports the ADA recommendation
      of use of a high-volume evacuator whenever ultrasonic scaling is performed.

PMID- 9766106
TI  - The efficacy of an intraoral fluoride-releasing system in irradiated head and
      neck cancer patients: a preliminary study.
AB  - This study compared the anticaries effectiveness of an intraoral fluoride
      releasing system, or IFRS, with a standard regimen of daily application of a 1.1
      percent neutral sodium fluoride gel in custom trays. Caries protection in
      subjects in the IFRS group was comparable to that in subjects in the 1.1 percent
      neutral sodium fluoride group. The subjects all had head or neck cancer and had
      received radiation therapy, but no more recently than three months before taking
      part in the study. Overall, IFRS devices were well-tolerated and patient
      satisfaction was high. The IFRS appears to offer several advantages over the
      daily application of fluoride gels in custom trays.

PMID- 9766107
TI  - How dentition status and masticatory function affect nutrient intake.
AB  - The authors examined nutrient intake in relation to the number of teeth, denture
      type and masticatory function among 638 men in the U.S. Department of Veterans
      Affairs Dental Longitudinal Study. They found that calorie-adjusted nutrient
      intakes decreased with progressively impaired dentition status, independently of
      age, smoking status and alcohol use. Intakes of fiber and most vitamins and
      minerals were inversely correlated with masticatory function. The findings
      suggest that prevention of tooth loss and prosthodontic replacement of missing
      teeth could improve diets of older adults.

PMID- 9766108
TI  - Eleven myths of dentoalveolar surgery.
AB  - Through the years, dentists who perform dentoalveolar surgery have perpetuated
      many myths and other unproven beliefs from one generation to another. Sometimes,
      these beliefs originated in older textbooks, while others were given birth by
      mentors sharing anecdotal experiences with their students. Even today, many of
      these scientifically unsupported statements are perpetuated in surgical textbooks
      and in continuing education forums and are passed on to students in dental
      schools. In today's evolving environment of evidence-based medicine and
      dentistry, these anecdotal observations do not withstand scrutiny. The purpose of
      this article is to review the more common surgical myths and to test their
      validity against scientific evidence.

PMID- 9766109
TI  - Selecting drugs for the pregnant dental patient.
AB  - When treating pregnant patients, dental practitioners should avoid prescribing
      some drugs routinely used for local anesthesia, sedation, analgesia or infection.
      Dental practitioners need to determine that the potential benefits of the drug
      required for the mother's dental care outweigh the risks to her fetus. This
      article briefly reviews the relative risks of therapeutic agents commonly used in
      dental care to help practitioners select the safest drugs for use by pregnant
      patients.

PMID- 9766110
TI  - A simple technique for adjusting and polishing a soft splint.

PMID- 9766111
TI  - Dental procedure fees 1975 through 1995: how much have they changed?
AB  - A shift toward diagnostic and preventive dentistry in the last two decades is
      evident from the change in the number of dental procedures performed, as well as
      the change in the percentage of time spent performing different types of
      procedures. During the period 1975 through 1995, the average nominal fees for
      selected dental procedures increased. Once inflation was taken into account,
      however, the increase in the average real fees charged was more modest.

PMID- 9766112
TI  - Pulp capping 1998.

PMID- 9766113
TI  - Building a dynamic picture of the dental and craniofacial complex: progress in
      imaging.

PMID- 9766114
TI  - The inappropriate patient.

PMID- 9766115
TI  - Improved clinical decision-making using the evidence-based approach.
AB  - This article summarizes the evidence-based approach, a comprehensive and rigorous
      method for evaluating information, improving decision-making and implementing
      clinical treatment. The participants in The American Academy of Periodontology
      World Workshop assessed the evidentiary status of periodontal and implant
      treatment using the evidence-based approach. The major goal of the Workshop was
      to improve treatment decisions by increasing the strength of the inference that
      practitioners can derive from the base of knowledge contained within the
      literature.

PMID- 9766116
TI  - Periodontal diseases: epidemiology and diagnosis.

PMID- 9766117
TI  - Prevention.

PMID- 9766118
TI  - Periodontal implications: medically compromised patients, older adults and
      anxiety.

PMID- 9766119
TI  - Periodontal implications: mucocutaneous disorders.

PMID- 9766120
TI  - Non-surgical pocket therapy: mechanical, pharmacotherapeutics, and dental
      occlusion.

PMID- 9766121
TI  - Non-surgical pocket therapy: mechanical, surgical pocket therapy.

PMID- 9766122
TI  - Periodontal regeneration around natural teeth.

PMID- 9766123
TI  - Mucogingival therapy.

PMID- 9766124
TI  - Implant therapy. I.

PMID- 9766125
TI  - Implant therapy. II.

PMID- 9766126
TI  - Periodontal diseases: pathogenesis and microbial factors.

PMID- 9766127
TI  - [Public health work and its advantages as a dilemma of the assessor. Subjective
      common sense is a good help].

PMID- 9766128
TI  - [Transplantation of the small intestine gives hope of improved survival].

PMID- 9766129
TI  - [The most extensive study of artificial insemination. Abnormalities are mostly
      common among children born after IVF].

PMID- 9766130
TI  - [Is the patient right? A comment to the report from HSU 2000].

PMID- 9766131
TI  - [Over-interpretation of the HOT and CAPP studies].

PMID- 9766133
TI  - [Correctly organized drug prescription registry is functioning well].

PMID- 9766132
TI  - [Treatment of tularemia in children].

PMID- 9766134
TI  - [Medical administrators are to blame for unacceptable work place conditions].

PMID- 9766135
TI  - [Avoid the mouse-trap! Musculoskeletal injuries can be reduced by placing the
      mouse within shoulder space].
AB  - Somewhat more than 50 per cent of computer operators complain of problems in the
      neck, shoulders or arms. A possible source of such problems may be manipulation
      of the mouse. Women are more susceptible than men, possibly due to their smaller
      physical size and muscle power. With the mouse placed to the side of the
      keyboard, narrow-shouldered computer operators must lift their arm and turn it
      sharply outwards. It is preferable to place the mouse within the span of the
      shoulders and rest the entire forearm on the desk. A shorter keyboard might be
      the answer for narrow-shouldered people.

PMID- 9766136
TI  - [Homozygous protein C deficiency can be detected by prenatal diagnosis].
AB  - Homozygous protein C deficiency (HPCD) with purpura fulminans is a rare condition
      with an estimated incidence of 1-2 per 400,000 births. About 20 case reports have
      appeared since the first one was published in 1983. HPCD provides an excellent
      illustration of the fundamental importance of the protein C anticoagulant
      pathway. This severe coagulopathy results in serious organ damage, often already
      in utero, and without treatment it is incompatible with life. The treatment
      options include fresh frozen plasma and protein C concentrate in the acute phase,
      followed by oral anticoagulant therapy. Over 160 different point mutations in the
      protein C gene have been identified in recent years, offering new possibilities
      for prenatal diagnosis. The article describes the case of a family who lost two
      children with congenital HPCD. But where the specific point mutation was
      identified thus enabling prenatal diagnosis to be performed in a subsequent
      pregnancy.

PMID- 9766137
TI  - [Rehabilitation after myocardial infarction or coronary surgery: elderly patients
      may benefit as much as the younger ones].
AB  - At most Swedish hospitals participation in cardiac rehabilitation programmes is
      restricted to patients of working age, although coronary patients predominately
      belong to the higher age groups. The article consists in a review of the benefits
      of cardiac rehabilitation to the elderly, such as enhanced quality of life and
      lower readmission rates, improvement in co-ordination, muscular strength and bone
      mineral constant, and a cardioprotective effect on risk factors. Cardiac
      rehabilitation programmes for the elderly, preferably organised in close so
      operation between local hospitals, primary care facilities and patient
      organisations, might yield considerable individual and general health economic
      benefits.

PMID- 9766138
TI  - [Chronic mesenteric ischemia. Endovascular treatment is as effective as open
      surgery].
AB  - Chronic mesenteric ischaemia is a rare but serious condition, which if untreated
      may cause death secondary to starvation or bowel infarction. As the symptoms are
      sometimes unspecific, its diagnosis may be delayed or missed. Although open
      surgical revascularisation has been the traditional treatment, a review of
      published reports suggests it to be associated with operative mortality rates of
      6-9 per cent, and major morbidity rates of 22-26 per cent. Reports by others, and
      our own experience, suggest that endovascular treatment of mesenteric
      atherosclerotic obstructions with PTA (percutaneous transluminal angioplasty) and
      stenting may yield patency rates differing little from those associated with
      surgery, but significantly lower mortality (1.6%) and morbidity (5.6%).

PMID- 9766139
TI  - [A developmental project at the pediatric department in Orebro. Physicians were
      asked to assess their own competence].

PMID- 9766140
TI  - [Tattooing as an aid within plastic surgery].

PMID- 9766141
TI  - [Vitamin B12 deficiency surveyed at two health care centers].

PMID- 9766142
TI  - [Public health work is improvement without impairment].
AB  - Strategies for community intervention, their evaluation and social patterning are
      discussed in the article. Theories and methods are called for to enable better
      assessment of social inequalities in health outcome variables and processes in
      public health endeavours. With this is a starting point some methodological and
      ethical issues relating to preventive programmes and their evaluation are
      identified.

PMID- 9766143
TI  - [Public health work needs new evaluation models. Primary care projects are more
      effective than large scale campaigns].
AB  - The need both of critical assessment of community intervention programmes and of
      alternatives to randomised controlled studies is discussed in the article.
      Examples are drawn from a review recently completed for the Swedish Council on
      Technology Assessment in Health Care [Statens Beredning for Utvardering av
      medicinsk metodik (SBU)], and from the evaluation of a cardiovascular disease
      prevention programme currently in progress in northern Sweden.

PMID- 9766144
TI  - [The Swedish scissors for plaster of Paris was a sensational discovery. Now more
      than 100 years old].

PMID- 9766145
TI  - [Should public health recommendations be given generously? Too high demands on
      the scientific basis can inhibit preventive work].

PMID- 9766146
TI  - [Cat women, fish boys, frog girls... The theory on "impressions in the womb"
      still had believers in the 20th century].

PMID- 9766147
TI  - [Culture in medicine: the meeting between expectations and unfamiliar health
      care].

PMID- 9766148
TI  - [200-year anniversary of an epoch-making dissertation on cow-pox. A unique copy
      with a dedication in Gothenburg].

PMID- 9766149
TI  - [Internationalization of medical education at the Karolinska Institute: students
      compare diagnosis and treatment of angina pectoris].

PMID- 9766150
TI  - [A special unit for acute cases resulted in shorter length of stay at the
      department of surgery].

PMID- 9766151
TI  - [University and health care authorities cooperate: new regional continuing
      education gives practical knowledge of research methods].

PMID- 9766152
TI  - Active listening to cancer patients' stories.
AB  - Approximately two thirds of all Dutch cancer patients have severe emotional
      problems; shortly after their change from the treatment regime into the regime of
      medical controls. Half of them even need professional support. It is, therefore,
      important that a professional listens with empathy to the patient's version of
      the illness story. Story telling helps to overcome the existential crisis of
      being a cancer patient; it is an essential step in the revalidation process.
      Themes and open questions which structure the communication are suggested in this
      article.

PMID- 9766153
TI  - Clinical presentation of sarcoidosis in The Netherlands an epidemiological study.
AB  - BACKGROUND: Patients suffering from sarcoidosis may present with a wide range of
      symptoms. The aim of this study was to make an inventory of the clinical
      presentation of the sarcoidosis population in the Netherlands. METHODS: Symptom
      inventory questionnaires were sent to all members of the Dutch Sarcoidosis
      Society. Of these 1755 sarcoidosis patients, 1026 (58%), (age 46.7 +/- 11.6,
      female 63%) completed the questionnaire. RESULTS: Familial sarcoidosis was
      reported by 170 patients (16.3%). In 57% of the cases the first diagnosis was
      sarcoidosis. Other diagnosis included rheumatoid arthritis (5.1%) and
      tuberculosis (4.8%). Treatment with systemic corticosteroids was reported by 565
      patients (55.1%). The most frequently reported symptom was fatigue (71%),
      followed by dyspnea (70%), arthralgia (52%), muscle pain (39), chest pain (27%),
      and general weakness (22%). Moreover, 26% of patients suffered from disease
      related tension and strain. No relationship was found between the reported
      symptoms and treatment with corticosteroids. CONCLUSIONS: Sarcoidosis patients
      suffered from a broad range of persistent physical symptoms. In this study
      fatigue appeared to be the most commonly reported symptom. Intervention programs
      should focus on physical health as well as psychosocial aspects such as teaching
      patients how to cope with the disease.

PMID- 9766154
TI  - Lipid peroxidation in type 2 diabetes: relationship with macrovascular disease?
AB  - BACKGROUND: Macrovascular disease is the leading cause of death in diabetes. The
      increased risk of atherosclerosis in diabetes may be partly explained by
      increased lipid peroxidation. METHODS: We assessed lipid peroxidation in subjects
      with type 2 diabetes with (n = 23) and without (n = 23) macrovascular
      complications versus healthy age-matched controls (n = 13). The diabetic groups
      were matched for glycemic control (mean HbA1c = 9%), and for age had similar
      known duration of diabetes. RESULTS: Plasma TBARS were comparable between
      diabetic subjects with and without macrovascular complications (1.89 +/- 0.32 and
      1.81 +/- 0.28 mumol/l) and elevated compared to healthy controls (1.64 +/- 0.26
      mumol/l, p = 0.025). Ratios of IgG and IgM antibodies to oxidized vs. native LDL
      were comparable between diabetic subjects and controls, and also between diabetic
      subjects with or without macrovascular complications. The lag phase, an index of
      the resistance of LDL to oxidation, was significantly longer in diabetic patients
      with macrovascular complications (66 +/- 8 min) vs. those without macrovascular
      complications and controls (resp. 59 +/- 7 and 56 +/- 7 min, p < 0.05). An
      explanation may be the frequent use of drugs with possible antioxidant potential,
      e.g. beta-blocking agents, ACE-inhibitors and calcium entry blockers by these
      patients. Surprisingly, plasma vitamin E levels were higher in diabetic subjects.
      CONCLUSIONS: We found no evidence of increased lipid peroxidation in diabetic
      subjects with macrovascular complications, but an increased resistance to
      oxidation in this group, probably due to an altered antioxidant status. The
      increased TBARS level in diabetic subjects contrasts with the other indices of
      lipid peroxidation and may be related to prevalent hyperglycemia and should
      therefore be interpreted cautiously.

PMID- 9766155
TI  - Chronic tophaceous gout in the elderly.
AB  - Gout in the elderly seems to represent a special subgroup. The presentation is
      often atypical and drug treatment poses special difficulties. We present two
      elderly patients with large subcutaneous tophi leading to grotesque deformities.
      Their clinical features, risk factors, diagnosis and treatment are discussed.
      Although the appearance and radiographic changes caused by tophi are
      characteristic, the definitive diagnosis of tophaceous gout is made by aspiration
      and crystal analysis, as is illustrated by colour photographs.

PMID- 9766156
TI  - Lymphocytic hypophysitis in a 43-year-old woman.
AB  - A woman with sarcoidosis and primary hypothyroidism presented with partial
      hypopituitarism without pituitary gland enlargement. A clinical diagnosis of
      lymphocytic hypophysitis was established after exclusion of other possibilities,
      since a definitive diagnosis can only be made after histological studies. This
      rare form of chronic inflammation and destruction of the anterior pituitary gland
      is discussed.

PMID- 9766157
TI  - Splenic epithelial cysts and splenomegaly: diagnosis and management.
AB  - Splenomegaly is a common problem. In the absence of systemic illness or
      malignancy splenic cysts must be considered, especially the epithelial variety.
      For large cysts total splenectomy has long been recommended. Recognition of the
      risk of an overwhelming postsplenectomy infection (OPSI), especially in children,
      has led to spleen conserving surgery. We describe the use of an absorbable Vicryl
      net after partial splenectomy with total cystectomy in the management of splenic
      epithelial cysts.

PMID- 9766158
TI  - An interactive approach to training teams and developing programs.
AB  - A combination of educational and organizational strategies help rehabilitation
      teams develop programs that effectively address the needs of their consumers.

PMID- 9766159
TI  - Training professionals for rehabilitation teams.
AB  - Transformed treatment philosophies, egalitarian roles, crossover competencies,
      and engagement of consumers and families are essentials in training.

PMID- 9766160
TI  - A systems approach to developing staff training.
AB  - This chapter shows how concepts from organizational psychology can be used to
      design a comprehensive staff training model for a statewide mental health service
      system, and emphasizes the importance of competency identification in this model.

PMID- 9766162
TI  - Developing effective team leaders.
AB  - For most staff, the most challenging leadership role they will play is their
      first. This chapter describes a research-based training program being developed
      to help these leaders increase their effectiveness in this first role.

PMID- 9766161
TI  - Total quality management in behavioral health care.
AB  - The literature on total quality management or continuous quality improvement in
      the behavioral health care field is just beginning to emerge. Although most of
      the evidence on its effectiveness remains anecdotal, it seems clear that it can
      work in behavioral health care organizations with strong leadership support and a
      long-term commitment.

PMID- 9766163
TI  - Training for state-funded providers of assertive community treatment.
AB  - This chapter describes a training program for state-funded providers of assertive
      community treatment services in Illinois and presents results of the evaluation
      of the didactic education component.

PMID- 9766164
TI  - Consumers as providers in psychiatric rehabilitation.
AB  - Issues that arise in employing consumers as providers in psychiatric
      rehabilitation programs include readiness of the sponsoring agency, consumer
      disclosure, and adjustments in employment practices. Psychiatric rehabilitation
      agencies are obligated to seriously consider employing consumers, since they
      frequently ask the same of the other organizations.

PMID- 9766165
TI  - Psychiatric rehabilitation technology: operationalizing the "black box" of the
      psychiatric rehabilitation process.
AB  - Psychiatric rehabilitation technology helps practitioners involve their consumers
      more fully in the process, act more forcefully on their behalf, and more
      accurately document the process and its outcomes.

PMID- 9766166
TI  - Burden on the families of patients with schizophrenia: results of the BIOMED I
      study.
AB  - The burden, the coping strategies and the social network of a sample of 236
      relatives of patients with schizophrenia, living in five European countries, were
      explored by well-validated assessment instruments. In all centres, relatives
      experienced higher levels of burden when they had poor coping resources and
      reduced social support. Relatives in Mediterranean centres, who reported lower
      levels of social support, were more resigned, and more often used spiritual help
      as a coping strategy. These data indicate that family burden and coping
      strategies can be influenced by cultural factors and suggest that family
      interventions should have also a social focus, aiming to increase the family
      social network and to reduce stigma.

PMID- 9766167
TI  - Social and clinical factors influencing the choice of coping strategies in
      relatives of patients with schizophrenia: results of the BIOMED I study.
AB  - The impact of social and clinical factors on the choice of coping strategies of a
      sample of 236 relatives of patients with schizophrenia, living in five European
      countries, was explored using well-validated questionnaires. The adoption of
      problem-focused coping strategies was more frequent among young relatives and
      among relatives of younger patients, and was associated with higher levels of
      practical and emotional social support and of professional help. In contrast,
      emotion-focused strategies were more frequently adopted by relatives who had been
      living longer with the patient and who had poorer social support. It is suggested
      that supportive and educational interventions should be provided as early as
      possible to relatives of patients with schizophrenia, which, in addition to
      having a practical focus, should also have a social focus, aiming at extending
      the family's social network.

PMID- 9766168
TI  - Sex differences in the course of depression: evidence from a longitudinal study
      of a representative sample of the Belgian population.
AB  - Outcome studies of major depression indicate high rates of relapse and
      chronicity, and social role theories imply that chronicity should be greater for
      women, together suggesting that the well-known sex difference in depression is,
      at least partially, the result of differences in chronicity. Due to a lack of
      prospective longitudinal research answers to this empirical question are missing.
      Furthermore, the results of the few available surveys of the general population
      are inconsistent, showing either higher chronicity for older women or a lack of
      sex differences in the overall course of depression. Using data from three waves
      of the Panel Study of Belgian Households (complete data for 3204 women and 2907
      men, aged 16 years and older) sex differences in the persistence of depressive
      behavior are estimated. Depression is measured using a self-report inventory on
      three occasions separated by intervals of 1 year (1992, 1993, 1994). Results show
      a significant influence of sex, other sociodemographic characteristics, and
      depression severity at baseline on depression persistence. Women experience more
      symptoms for a longer period of time, a difference that can be partially ascribed
      to sex differences in employment status, education and marital status. The
      findings are discussed.

PMID- 9766169
TI  - Avoidable mortality among psychiatric patients.
AB  - Avoidable mortality is a selection of causes of death considered to be amenable
      to health care and thereby used as an indicator of the quality of health care. In
      this study avoidable mortality for more than 30,000 psychiatric patients
      discharged from any hospital of Stockholm County between 1981 and 1985 has been
      followed up in the Cause of Death Register for the period 1986-1990. Standardised
      rate ratios were calculated for different groups of psychiatric disorders
      compared to the general population of Stockholm County for indicators of
      avoidable mortality, suicide, other mortality ("unavoidable") and causes possibly
      related to treatment with psychotrophic drugs. As expected, the psychiatric
      patients had the most pronounced elevated risk for suicide. i.e. 6- to 24-fold
      compared to the general population, and noticeably more elevated for women. It is
      also noteworthy that the relative mortality risks for diagnoses amenable to
      medical interventions and potential side-effects of psychotrophic drugs are
      higher than for other causes of death ("unavoidable"). The relative risks for
      avoidable mortality were 4.7 for men and 3.8 for women and for diagnoses possibly
      related to side-effects of psychotrophic drugs, 7.2. The relative risks for
      "unavoidable" mortality were 3.4 for men and 3.2 for women. The excess avoidable
      mortality rates for psychiatric patients and the elevated suicide risk,
      especially for female patients, are warning signals of shortcomings in
      psychiatric care that warrants further investigation.

PMID- 9766171
TI  - Abuse of and dependence on alcohol in Swedish women: role of education,
      occupation and family structure.
AB  - The present study, which is part of a multipurpose study on alcohol use among
      women, focuses on the association between education, occupation, family structure
      and development of alcohol dependence or abuse in women. A total of 316 women
      were selected by stratified random sampling from all women in a defined part of
      Gothenburg, Sweden. In a face to face interview, questions were asked about
      occupation, education, family structure and other variables reflecting
      socioeconomic conditions and relations within the family. As outcome measures we
      used alcohol dependence and abuse (ADA), diagnosed in a clinical interview
      according to the Diagnostic and Statistical Manual of Mental Disorders, Third
      Edition-Revised (DSM-III-R). We found that never having been married, or having
      poor communication with the spouse, as well as having no children at home to take
      care of, were strongly associated with ADA in women. The role of social class
      depended on whether education or occupation was used as a measure. Our findings
      are compatible with the hypothesis that development of alcohol-related problems
      among women to a large extent is influenced by matters that relate to home and
      private life.

PMID- 9766170
TI  - The TAPS project 32: social networks of two group homes ... 5 years on. Team for
      the Assessment of Psychiatric Services.
AB  - Long-stay psychiatric patients discharged to two group homes from Friern Hospital
      were studied 1 year and 5 years after discharge. A much greater cohesiveness of
      social relationships was noted in the smaller home at both time points, whereas
      in the larger home residents had failed to develop friendships and intimacy
      within their social group. A number of hypotheses were explored to explain this
      difference. None of the factors investigated provided an explanation, including
      the mental state of the patients prior to discharge, their problems of social
      behaviour, the size of the group homes, whether they were staffed or unstaffed,
      and the patients' age. However, the development of friendships and intimacy over
      a 5-year period was strongly determined by the quality of the patients' social
      networks while in hospital. Consequently, when selecting groups of patients to
      share homes in the community, it is deemed advisable to form groups that fully
      reflect the range and diversity of their social networks.

PMID- 9766172
TI  - The Italian version of the Family Assessment Device.
AB  - The aim of the study was to evaluate in a heterogeneous. Italian sample (n = 340)
      the psychometric properties of the Italian version of the Family Assessment
      Device (FAD), a 60-item questionnaire assessing family functioning. The
      questionnaire was administered to psychiatric (n = 116), medical (n = 114) and
      non-clinical samples (n = 110). In a sample of 30 non-clinical subjects the
      temporal stability of the FAD was investigated. The results showed a good
      temporal stability for Problem Solving, General Functioning. Communication, and
      Affective Responsiveness scales, and a good internal reliability of the scale.
      Factor analysis of the Italian version provided discrepancies with the
      hypothesized structure of the instrument, leading to the identification of seven
      slightly different dimensions. The proposed seven-factor model of the instrument
      did not provide a good fit to our data. The results of our study suggest the need
      for a major improvement in the adaptation of the FAD in the Italian setting.

PMID- 9766173
TI  - The nitroxidergic neuron in central and peripheral nervous system and related
      paraneural structures.

PMID- 9766175
TI  - After your heart attack.

PMID- 9766174
TI  - Dental microwear. Morphological, functional and phylogenetic correlations.
AB  - Dental wear, at first considered a pathological condition, is now regarded as a
      physiological mechanism of teeth adaptation to continuous masticatory stresses.
      Excessive wear is limited by characteristic structural adaptations of dental hard
      tissues showing a phylogenetic trend and specialisation. Enamel is the main
      tissue subjected to wear; however, advanced enamel wear exposes increasingly
      large areas of dentine. Enamel hardness and anisotropy are the major factors
      contrasting wear and microfractures. Anisotropy is mainly related to the
      different orientation of prism bundles (and of hydroxiapatite cristals). Enamel
      wear development is also related to differences in microhardness, density,
      mineral composition and protein distribution. Masticatory loads distributed along
      the enamel-dentine junction uniformly disperse in the underlying dentine. In
      spite of its structural characteristics, dentine is relatively isotropic by the
      functional point of view. Even if its lower hardness opposes less efficaciously
      to wear, its biomechanical characteristics successfully contrast microfractures.
      The study of microwear (namely the microscopic analysis of worn dental surfaces)
      can be made both on original surfaces and on high definition silicone-resin
      replicas. Scanning electron microscope observations allow identification of
      surface damage (microtraces) produced by different physical and chemical agents.
      Microwear analysis may provide indications about alimentary and non alimentary
      habits, masticatory biomechanics and pathological situations (e.g., bruxism).

PMID- 9766176
TI  - Herbs for the prostate.

PMID- 9766177
TI  - Teaching hospitals score well.

PMID- 9766178
TI  - I am 61 years old, and for about six years I've been taking Mevacor for my
      cholesterol. My doctor is pleased with my results, but I read a newspaper ad that
      said Pravachol was better. Should I ask for a new prescription?

PMID- 9766179
TI  - Should you take drugs for cholesterol?

PMID- 9766180
TI  - Kicking painful leg cramps.

PMID- 9766181
TI  - Dizziness: preserving your sense of balance.

PMID- 9766182
TI  - New hope for Parkinson's disease.

PMID- 9766183
TI  - Is it a good idea to have a chest x-ray as part of a routine physical?

PMID- 9766184
TI  - Does tooth bleaching work and is it safe?

PMID- 9766185
TI  - What is a CEA test?

PMID- 9766186
TI  - Etienne-Jules Marey, founder of the graphic method.

PMID- 9766187
TI  - Localization of Myf-5, MRF4 and alpha cardiac actin mRNAs in regenerating Xenopus
      skeletal muscle.
AB  - We have analysed the spatial and temporal expression patterns of Myf-5, MRF4 and
      alpha cardiac actin mRNAs during muscle regeneration following cardiotoxin injury
      in adult Xenopus laevis using in situ hybridization. Myf-5 transcripts began to
      be detected in the activated satellite cells as early as the beginning of the
      regeneration process, then dramatically decreased in young plurinucleated
      myotubes. MRF4 mRNA was detected later, just before the young myotube stage, and
      was strongly expressed during the different stages of the maturation of myotubes.
      Like Myf-5, alpha cardiac actin mRNA began to accumulate early in activated
      satellite cells. These results, which contribute to an overview of the expression
      of the genes coding for myogenic bHLH proteins during muscle regeneration, are
      discussed in relation to the expression of these factors during development.

PMID- 9766188
TI  - Hb Nancy and Hb Osler: two distinct genetic variants with identical clinical and
      hemoglobin phenotype.
AB  - Three hemoglobin variants (Hb Nancy, Osler and Fort Gordon), carrying the same
      Tyr-->Asp substitution at position beta 145 (HC2), have been independently
      described in 1975 in patients with marked polycythemia. The first one was found
      in a French caucasian family from Lorraine, and the two others in African
      Americans. Two unrelated individuals with Hb Osler have been recently
      reinvestigated at the DNA level and surprisingly, in their beta gene, codon 145
      was found to be AAT which encodes for asparagine and not for aspartic acid, the
      aspartate at the protein level resulting, thus, from a very efficient
      posttranslational event. We reinvestigated a patient from the family of Hb Nancy
      and found that codon 145 was GAT, encoding for aspartate. This demonstrates that
      Hb Nancy is genetically distinct from Hb Osler despite an almost identical
      phenotype.

PMID- 9766189
TI  - Trajectory formation and speed-accuracy trade-off in aiming movements.
AB  - The trade-off between speed and accuracy and the patterning of movement
      kinematics have been central issues for theories of human movement for almost a
      century. In the present contribution experimentally obtained kinematics of
      reciprocal aiming movements, performed under different task conditions, are
      modelled as resulting from a single non-linear dynamical system whose parameters
      vary so as to respond to the task demands. Providing a unified account of speed
      accuracy trade-off and trajectory formation phenomena, the model offers a
      theoretical framework in which both discrete and continuous movements, performed
      along one or more dimensions can be understood.

PMID- 9766190
TI  - [Frequency of the coreceptor CCR5 gene delta 32 mutation in different French
      regions].
AB  - We studied the frequency of the coreceptor CCR5 gene delta 32 mutation on 1,836
      DNA samples originating from ten French regions. This mutation confers, in the
      homozygous state, resistance to HIV-1 infection. For the whole territory, the
      mean percentage presence of the delta 32 mutation is 9.2%. The mutation is
      statistically more frequent in the north (11.2%) than in the south (6.3%) of the
      country; this differentiation corresponds probably to a gradient of decreasing
      frequencies of the delta 32 mutation in Europe.

PMID- 9766191
TI  - Diets enriched in (n-3) fatty acids affect rat coagulation factors dependent on
      vitamin K.
AB  - The effects of dietary lipids on haemostasis were investigated in rats fed high
      fat diets enriched in saturated fatty acids (SAT), oleic acid (OLEIC), MaxEPA oil
      (MaxEPA), eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) and results
      were compared to those for rats fed standard chow (ST). Coagulant activities of
      factor IIc and factor VII-Xc were reduced by about 70% in the MaxEPA group and
      50% in the EPA and DHA groups relative to the OLEIC, SAT and ST groups. Liver
      vitamin K levels were five times lower in the experimental groups than in the ST
      group, which would indicate an effect of high fat diets on vitamin K metabolism.
      However, only (n-3) fatty acids prolonged the prothrombin time. These components
      could act at the post-translational modification level of vitamin K-dependent
      plasma clotting factors. The changes in haemostatic factors found in the MaxEPA
      group were counteracted by vitamin K supplementation.

PMID- 9766192
TI  - [Computer assisted open heart surgery. First case operated on with success].
AB  - The recent development of less invasive intracardiac surgery using small
      incisions and videoscopic techniques allowed an evaluation of the advantages and
      limitations of this new approach. Among the limitations was the increased
      difficulty of the surgical technique when using long instruments through small
      incisions and ports. We investigated whether computer assisted surgical
      instruments might bring a solution to this problem. Among the existing systems,
      we selected the Intuitive System because of two original features. It provides a
      stable, magnified, three dimensional view of the operating field at a console
      where the surgeon is seated to operate, and it uses computer assisted instruments
      having the same dexterity and range of motion as the hand. After 10 months of
      active work to adapt this system to intracardiac surgery, the first open heart
      operation using computer assisted instruments was carried out on a 52-year-old
      woman presenting an aneurysm and a large defect of the atrial septum. The patient
      was extubated 8 h after the operation, returned to her room 16 h later and was
      discharged from the hospital 8 d post-operatively with normal heart function and
      no residual shunt. This preliminary experience showed that computer assisted
      cardiac surgery is feasible and may open new and promising directions in open
      heart surgery.

PMID- 9766193
TI  - [The discovery of anaphylaxis: 19 days after an anodyne account of toxicology, it
      is shown that immunity is perhaps pathogenic].
AB  - While studying the toxicology of various coelenteres fishing filament poisons,
      Charles Richet and Paul Portier observed cases of rapid death which had no
      correlation with the injected doses. In dogs, death only occurred in those which,
      more than 15 days beforehand, had withstood well an injection more concentrated
      or identical to the later fatal one. The authors created the neologism
      'anaphylaxis' which signifies 'non-protection'. Thus, it appeared that an immune
      response could be pathological. This discovery opened the subject area of
      immunopathology at a period of time when, in contrast, vaccination and
      serotherapy researches were prominent.

PMID- 9766194
TI  - Dihydroorotate (dhout) and orotate (orout) utilizer mutants in yeast:
      identification of the dhout mutation and allelism of the DHO and URE2 genes.
AB  - We induced by UV mutagenesis a series of yeast mutants that were able to utilize
      dihydroorotic (dhout) and orotic acid (orout) as precursors for pyrimidine
      biosynthesis. These recessive mutations defined three complementation groups
      named dhout, orout1 and orout2. The wild-type allele of the gene responsible for
      dihydroorotate utilization was cloned using the sensitivity of the dhout mutant
      to 5-fluoroorotate. The DHO gene was sequenced and found to be identical to the
      URE2 gene. The dhout mutation resulted from the introduction of a stop codon
      instead of a glutamine at position 59, which led to the production of a truncated
      Ure2p. Therefore, the URE2 and DHO genes are alleles in yeast.

PMID- 9766195
TI  - [Substance P in the primary sensory neurons innervating the dental pulp in the
      guinea pig].
AB  - Primary sensory trigeminal neurons supplying the dental pulp of incisors in
      guinea pigs were labelled by retrograde axonal transport. Using an
      autometallographic intensification procedure, 48 h after injection of wheat germ
      agglutinin/colloidal gold in the pulp, gold particles were detected in the
      cytoplasm of the neurons as black granulations. A morphometric study showed a
      bimodal repartition of the labelled neurons of the ganglion. By submitting
      ganglion slices to an anti-substance P immunserum revealed by
      immunocytochemistry, it could be observed that, among the neurons supplying the
      dental pulp of incisors, the majority of the largest were substance P
      immunopositive while the smallest were substance P immunonegative. These
      observations suggest that there could be at least two different populations of
      nerve fibres supplying the guinea pig incisor dental pulp. Substance P negative
      neurons could express different neurotransmitters.

PMID- 9766196
TI  - Lateral dynamic balance reactions to circular translation of the visual field.
AB  - Lateral sway of subjects in spontaneous dynamic balance conditions on a seesaw
      platform was measured during a visual stimulation monocularly produced by a
      rotating glass covered with a prism membrane. Prism rotation induced the
      perception of a circular translation of the whole visual field and an ocular
      pursuit movement. Therefore, the retinal slip that occurs in normal pursuit was
      cancelled. Strong stereotyped postural reactions were observed in a direction
      that depended upon both the vertical visual field deviation and the eye
      stimulated: upper position of the right visual field induced a leftward sway
      resulting from an extension of the right hemibody; symmetrical reactions occurred
      for the left stimulation. The results suggest that the postural reactions
      recorded depend on the isolated oculomotor activity and, in addition, on retinal
      afferences corresponding to the temporal crescent of the stimulated side, which
      orientates the postural reaction on the homolateral lower limb muscles.

PMID- 9766197
TI  - [Radiation-induced DNA fragmentation evaluated by anti-poly(ADP
      ribose)immunolabeling in CHO cells. Standardization with pulsed-field
      electrophoresis].
AB  - The poly (ADP-ribose) polymerase is an ubiquitous nuclear protein capable of
      binding specifically to DNA strand breaks. It synthesizes ADP-ribose polymers
      proportionally to DNA breaks. The actual method of reference to determine DNA
      double strand breaks is pulsed-field gel electrophoresis, but this requires many
      cells. It thus appeared of interest to use poly (ADP-ribos)ylation to follow and
      estimate gamma-ray-induced DNA fragmentation at the level of isolated cells after
      gamma-irradiation in chinese hamster ovary cells (CHO-K1). The results obtained
      by the immunolabelling technique of ADP-ribose polymers were compared to those
      obtained by pulsed-field gel electrophoresis. They show that poly (ADP
      ribos)ylation reflects the occurrence of radiation-induced DNA strand breaks. A
      clear relationship exists between the amount of ADP-ribose polymers detected and
      DNA double strand breaks after gamma-irradiation.

PMID- 9766198
TI  - Comparison of 14 PCR systems for the detection and subtyping of stx genes in
      Shiga-toxin-producing Escherichia coli.
AB  - The specificity of 14 polymerase chain reaction (PCR) systems designed for the
      detection and subtyping of stx genes was tested on a set of Escherichia coli
      strains with known sequences of stx genes. Systems designed for the detection of
      genes of the stx1 type did not detect any variant genes of the stx2 type and
      conversely, no stx2 type-specific systems detected stx1 variant genes. Among five
      stx2 type-specific systems, none detected the stx2ev gene, and two detected the
      stx2e gene. Among systems designed for screening genes of the both stx1 and stx2
      types with a single primer pair, only one system (the Lin system) was able to
      detect stx genes in all studied strains. Shiga-toxin-producing E. coli frequently
      carry more than one stx variant gene. Coamplification of stx genes present in the
      same strain was demonstrated by restriction of PCR products with endonucleases
      generating fragments of variant-specific size. The amplification product obtained
      by the Lin system restricted by Hincll yielded fragments of different size for
      stx1, stx2, stx2c, stx2e and stx2ev. Thus it was possible to identify different
      genes carried in a single strain with a simple two-step PCR/endonuclease
      restriction protocol.

PMID- 9766199
TI  - Colonization ability and pathogenic properties of a fim- mutant of an avian
      strain of Escherichia coli.
AB  - Several studies suggest that the expression of type 1 fimbriae is involved in the
      virulence of Escherichia coli in chickens, by promoting adhesion of bacteria to
      the respiratory tract, which is most probably the first step to occur in the
      infection, and by interacting with the immune response. In order to determine to
      what extent type 1 fimbriae were involved in the pathogenic process, the fim
      cluster of an avian pathogenic strain of E. coli, MT78 (O2:K1:H+), was modified
      in vitro and reintroduced in the parent strain via allele exchange using suicide
      vector pCVD442. The mutant strain thus generated (DM34) had its entire fim
      cluster removed. Its pathogenic properties were compared to those of the parent
      strain in an experimental reproduction of avain colibacillosis in 15-day-old
      chickens, after primary infection with infectious bronchitis virus followed by
      intratracheal inoculation of the challenge strain. In specific-pathogen-free
      (SPF) animals, mutant DM34 was less pathogenic than the parent strain and
      colonized the lungs of infected animals to a lower level. In germ-free chickens,
      although DM34 was less pathogenic than MT78 according to the differences in
      weight gains, it colonized the trachea, lungs and internal organs to the same
      extent as MT78. Our results suggest that, whereas type 1 fimbriae are not
      strictly required in colonization of the respiratory tract of germ-free chickens,
      they might be important in establishing a bacterial population in the lungs of
      SPF animals. The difference regularly observed in weight gains between mutant-
      and wild-type-inoculated chickens reflects a decreased pathogenicity of the fim-
      mutant. However, the isolation of E. coli in target organs and the observation of
      colibacillosis symptoms and lesions in mutant-inoculated chickens suggest that
      type 1 fimbriae by themselves play a limited role in pathogenicity.

PMID- 9766200
TI  - Inactivation of mycobacteriophage D29 using ferrous ammonium sulphate as a tool
      for the detection of viable Mycobacterium smegmatis and M. tuberculosis.
AB  - There is still an urgent requirement for more sensitive, cost-effective methods
      for detection and susceptibility testing of mycobacteria in clinical samples. We
      have been investigating a simple bacteriophage-based system which could be used
      for both purposes. As this depends upon the detection of phages which have
      successfully infected cells, a key step is the efficient removal or inactivation
      of phages remaining free in the culture medium. We demonstrate here the use of
      ferrous ammonium sulphate as an effective agent for the inactivation of
      mycobacteriophage D29 without impairing phage replication in previously infected
      host bacteria. Using this property, we report the detection of viable
      Mycobacterium smegmatis, M. bovis BCG and M. tuberculosis using simple low-cost
      technology. The method is highly sensitive, since it is able to detect 10 colony
      forming units of M. smegmatis. It is also rapid, with the detection of M.
      tuberculosis in sputum specimens within 48 h.

PMID- 9766201
TI  - Genetic diversification of methicillin-resistant Staphylococcus aureus as a
      function of prolonged geographic dissemination and as measured by binary typing
      and other genotyping methods.
AB  - The aim of the present study was to determine the extent of genome evolution
      among methicillin-resistant Staghylococcus aureus (MRSA) strains. Three different
      collections of strains were analysed, comprising locally, nationally and
      internationally disseminated genotypes. Various genotyping assays displaying
      different levels of resolution were used. Geographically and temporally diverse
      MRSA strains comprised the international group. MRSA strains recovered during an
      outbreak in a New York City hospital and Portuguese MRSA isolates, all resembling
      the so-called Iberian clone, were included in the local and national collections,
      respectively. Genotypes were determined by genome scanning typing techniques and
      procedures which analyse specific DNA elements only. The outbreak strains showed
      subclonal variation, whereas the Portuguese isolates displayed an increased
      number of genotypes. Among the epidemiologically unrelated MRSA strains, the
      different genotyping techniques revealed a wide heterogeneity of types. Different
      typing techniques appeared to show different levels of resolution, which could be
      correlated with the extent of geographic spread; the more pronounced the spread,
      the higher the degree of genome evolution. Binary typing and randomly amplified
      polymorphic DNA analysis are the typing methods of choice for determining
      (non)identity among strains that have a recent common ancestor and have undergone
      yet limited dissemination.

PMID- 9766202
TI  - Differentiation of Brucella melitensis, B. ovis and B. suis biovar 2 strains by
      use of membrane protein- or cytoplasmic protein-specific gene probes.
AB  - The possibility of differentiating Brucella species and biovars by Southern blot
      hybridization of agarose gel-electrophoresed HindIII-digested genomic DNA with
      membrane protein- or cytoplasmic protein-specific gene probes was investigated on
      92 reference and field strains representative of all known species and biovars.
      Based on the RFLP pattern observed, three gene probes, i.e. br25, 39ugpa and
      omp16 coding for membrane or cytoplasmic proteins differentiated B. melitensis,
      B. ovis and B. suis biovar 2 strains from each other and from the other Brucella
      species and biovars. Thus, the use of these specific gene probes could
      contribute, in addition to previously identified species- or biovar-specific
      markers, to the molecular identification and typing of Brucella isolates.

PMID- 9766203
TI  - Development of a polymerase chain reaction assay for identification and detection
      of the fish pathogen Flavobacterium psychrophilum.
AB  - A PCR-based method was developed to identify and detect Flavobacterium
      psychrophilum, the causative agent of "cold-water disease" and "rainbow trout fry
      syndrome" in salmonid fish. Two oligonucleotide primers were designed by
      comparing the 16S rRNA sequence of all taxa in the genus Flavobacterium and of
      representative species in most related genera within rRNA superfamily V. Purified
      chromosomal DNAs from all these bacterial species, from 25 F. psychrophilum
      isolates and from several other fish-pathogenic bacteria were used to assess the
      specificity of the reaction. Amplification products were generated only with F.
      psychrophilum DNA. The detection level, equivalent to approximately 10 to 100
      bacterial cells, was increased 10-fold by hybridization with a radioactive probe.
      Preliminary experiments demonstrated that this procedure can also be applied to
      samples of infected tissue. This PCR assay is therefore a rapid, specific, and
      sensitive alternative to conventional plate culture methods for the
      identification and detection of F. psychrophilum.

PMID- 9766204
TI  - Pleiotropic mutations alter the kinetics of calcium transport, competence
      regulation, autolysis and experimental virulence in Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae is a pathogen in which the extracellular calcium
      concentration plays a major physiological role, in growth as well as in the
      induction of competence for genetic transformation and activation of autolysis.
      Both responses are under the control of a protein activator exported in the
      medium. We have checked the impact of mutations which alter the regulation of
      competence and autolysis on experimental virulence. Isogenic encapsulated
      derivatives carrying the relevant mutations were serotype 3 smooth clones,
      obtained by transformation of the relevant rough strains with DNA from a serotype
      3 smooth isolate. Survival kinetics and bacterial clearance from the blood were
      followed after intraperitoneal infection of Swiss mice with the different
      bacterial cultures. In this model, mutants showing an attenuation of virulence
      relative to the wild type fell into two classes. In the first, represented by the
      lytA::ery mutant V1095 defective for calcium-induced autolysis, attenuated
      virulence could be correlated with rapid bacterial clearance from the blood. In
      the second, represented by the dmb mutants V2200 and V3300, attenuation was
      associated with delayed bacterial clearance from the blood, and correlated with
      altered kinetics of calcium transport and of regulation of competence and
      autolysis. It appeared unlikely that attenuation of virulence for strains V2200
      and V3300 was a direct consequence of their competence phenotype, since the
      com::ery mutants V1008 and V1019, defective for the production of the competence
      activator, were as virulent as the wild-type strain. Autolysis involving an N
      acetyl-muramyl-alanine amidase encoded by lytA was also regulated by calcium. The
      inserted allele lytA0::ery further reduced virulence in the dmb1 background
      (V2200). This additive effect of lytA- to dmb1 points to different routes of
      virulence regulation by LYT and DMB1 and suggests that the kinetics of calcium
      traffic controls several pathways involved in the virulence of pneumococcus.

PMID- 9766205
TI  - A role for H-NS in the regulation of the virF gene of Shigella and enteroinvasive
      Escherichia coli.
AB  - We have investigated the role of H-NS, one of the major components of the
      bacterial nucleoid, in the expression of the virF gene present on the large
      virulence plasmid of Shigella and enteroinvasive Escherichia coli in response to
      different environmental conditions. VirF is an AraC-like protein which activates
      at least two promoters, virB and virG, both repressed by H-NS. Band shift
      experiments reveal that the affinity of H-NS for the virF and virB promoters is
      comparable, while the affinity for the virG promoter is higher. Polyacrylamide
      gel electrophoresis of three DNA fragments containing the virF, the virB and the
      VirG promoters demonstrates, in agreement with computer predictions, that they
      have an intrinsically curved structure, confirming the preference of H-NS for
      bent DNA. In vivo transcriptional analysis of virF mRNA shows that H-NS
      negatively controls the expression of virF at 30 degrees C. The expression of a
      virF-lacZ translational fusion in E.coli wild type and in an hns-defective
      derivative grown at 30 degrees or 37 degrees C and at pH 6.0 or 7.0 indicates
      that, in the absence of H-NS, virF expression becomes insensitive to temperature
      and to limited pH changes. Our results strongly suggest that H-NS controls virF
      expression by binding to the virF promoter and by repressing its expression at
      low temperature and at low pH.

PMID- 9766206
TI  - Superficial hydrophobicity in Serratia marcescens strains of clinical origin.

PMID- 9766207
TI  - Arguments against the involvement of Borrelia burgdorferi sensu lato in
      Alzheimer's disease.
AB  - The involvement of spirochaetes, such as the aetiologic agent of Lyme
      borreliosis, Borrelia burgdorferi sensu lato, in Alzheimer's disease (AD), a
      common neuropathology, has been proposed by several groups in the past. In our
      laboratory, brains from 10 AD patients were analysed for the presence of B.
      burgdorferi sensu lato by both standard and nested PCR techniques based on
      various target regions, such as the hbb gene (encoding the histone-like protein
      HBb), the fla gene (flagellin), the rrl-rrf ribosomal intergenic spacer region
      and the rrs gene (encoding 16S rRNA). In addition, ELISA and Western blot tests
      for the detection of antibodies against spirochaetal antigens were performed on
      27 sera from clinical AD patients. Using these methods, we did not obtain any
      evidence of the involvement of B. burgdorferi in Alzheimer's disease.

PMID- 9766208
TI  - Use of the C3H/He Lyme disease mouse model for the recovery of a Spanish isolate
      of Borrelia garinii from erythema migrans lesions.
AB  - A skin biopsy from a patient with erythema migrans was inoculated into C3H/He
      mice and into culture medium. A Borrelia garinii strain named Rio1 was isolated
      from both a direct BSK medium culture and a mouse ear-punch biopsy culture.
      Inoculating human tissue into mice produced a disease resulting in severe
      inflammation of the left tibio-tarsal joint, development of perivascular
      infiltrates as seen in ear-punch biopsies and the spread of spirochaetes along
      the skin, far from the inoculation site. The isolation of this strain confirms
      the circulation of this Borrelia species in Spain as a human pathogen, as well as
      its arthrogenicity in an animal model. The method used to recover strain Rio1
      from human tissue is described as rapid and sensitive compared to direct
      inoculation of tissue into BSK medium.

PMID- 9766209
TI  - Prevalence and characteristics of necrotoxigenic Escherichia coli CNF1+ and CNF2+
      in healthy cattle.
AB  - From February to July of 1994, 328 faecal samples from 32 herds were collected
      and examined for necrotoxigenic Escherichia coli (NTEC). Strains producing the
      cytotoxic necrotizing factors type 1 (CNF1) and type 2 (CNF2) were found on 4 and
      63% of the farms, respectively. The proportion of animals infected within each
      herd varied from 0 to 38%. NTEC producing CNF2 were significantly more frequently
      isolated from calves (24%; 17 of 71) than from cows (4%; 11 of 257) (chi 2corr.
      25.088; P < 0.001). Although the bovine CNF2+ strains belonged to 16 different
      serogroups, 5 (O15, O77, O88, O142 and O153) accounted for 44% of strains. This
      study confirmed that healthy cattle are a reservoir of NTEC producing CNF2, and
      revealed that CNF2+ strains are more frequently carried by calves than by adult
      cows.

PMID- 9766211
TI  - Heterotrophic growth on phenolic mixtures by Ochromonas danica.
AB  - Because phenols are one of the most common groups of organic pollutants in the
      aquatic environment, heterotrophic growth-linked biodegradation of phenol and its
      methylated homologues by the eukaryotic alga Ochromonas danica (CCAP 933/2B) was
      investigated. The alga grew heterotrophically on phenol and mixtures of phenol
      with o- or p-cresols, or with 2,5-, 2,6-, 3,4- or 3,5-xylenols as the sole
      sources of carbon in the dark at 25 degrees C. Commensurate with growth, the alga
      removed phenol, both cresol isomers and 2,5- and 3,4-xylenols from the growth
      media over the incubation periods. In every case, phenol was removed
      preferentially to the methylated cosubstrates, but the rates of removal for
      phenol were slower than in incubations where phenol was the sole carbon source.

PMID- 9766210
TI  - Genetic and serological analysis of the immunogenic 67-kDa lipoprotein of
      Mycoplasma sp. bovine group 7.
AB  - The gene encoding a lipoprotein of 67 kDa, named P67, was cloned from Mycoplasma
      sp. bovine group 7 strain PG50 and expressed in Escherichia coli K12. Analysis of
      the amino acid sequence derived from the DNA sequence of the P67 gene revealed a
      typical prokaryotic signal peptidase II membrane lipoprotein lipid attachment
      site and a transmembrane structure domain in the leader sequence at the amino
      terminal end of the protein. Protein P67 showed 91% identical amino acid residues
      to the lipoprotein P72 of Mycoplasma mycoides subsp. mycoides small colony type
      (SC) and 53% identical amino acid residues to a peptide of an unassigned gene on
      the genome of Mycoplasma capricolum subsp. capricolum. Antibodies made against
      recombinant P67 reacted with a 67-kDa protein in all Mycoplasma sp. bovine group
      7 strains tested and also, to some extent, with P72 of Mycoplasma mycoides subsp.
      mycoides SC. The gene encoding P67 was present in all strains of Mycoplasma sp.
      bovine group 7 analysed, but not in other Mycoplasma sp. of the "mycoides
      cluster" and not in the phylogenetically related Mycoplasma putrefaciens. PCR and
      restriction fragment analysis revealed that the gene of P67 is conserved in all
      strains of Mycoplasma sp. bovine group 7. A specific PCR reaction based on the
      P67 gene sequence enabled rapid identification of strains belonging to Mycoplasma
      sp. bovine group 7.

PMID- 9766212
TI  - Transport of glucose by a phosphoenolpyruvate:mannose phosphotransferase system
      in Pasteurella multocida.
AB  - Pasteurella multocida was examined for glucose and mannose transport. P.
      multocida was shown to possess a phosphoenolpyruvate (PEP):mannose
      phosphotransferase system (PTS) that transports glucose as well as mannose and
      was functionally similar to the Escherichia coli mannose PTS. Phosphorylated
      proteins with molecular masses similar to those of E. coli mannose PTS proteins
      were visualized when incubated with 32P-PEP. The presence of an enzyme IIAGlc
      which could play an important role in regulation, as described in other Gram
      negative bacteria, was detected. The enzymes of the pentose-phosphate pathway
      were present in P. multocida growth on glucose. The activity of 6
      phosphofructokinase (the key enzyme of the Embden-Meyerhof pathway (EMP)), was
      very low in cell extracts, suggesting that EMP is not the major pathway for
      glucose catabolism.

PMID- 9766213
TI  - Characterization and gene sequencing of a 19-kDa periplasmic protein of
      Campylobacter jejuni/coli.
AB  - In order to study a 19-kDa protein (p19) of Campylobacter jejuni, we purified
      this protein to homogeneity from C. jejuni strain 81,176 by anion exchange
      chromatography. The molecular weight of the native protein is 19,000 daltons. P19
      was found to be acidic with an isoelectric point of 4.8 and was located in the
      periplasmic space of the bacteria. The 20 N-terminal amino acids were sequenced
      and no significant similarities with known proteins were shown. A monoclonal
      antibody showed that p19 is conserved in the 2 species C. jejuni and C. coli.
      Analysis of sera from 23 patients with a Campylobacter-related infection
      indicated that p19 is not immunogenic during natural infection in man. The gene
      encoding p19 was cloned and no strong homologies with known sequences were
      identified. The preparation of a knockout mutant in p19 will enable the
      investigation of the function of this cell wall component of Campylobacter.

PMID- 9766214
TI  - Implication of cell wall constituents in the sensitivity of Kluyveromyces lactis
      strains to amphotericin B.
AB  - In Kluyveromyces lactis, the cell wall compositions of Kl (ATCC 96897), a wild
      sensitive strain, and Klm (ATCC 96896), a strain resistant to amphotericin B
      (AmB), were shown to be very different, since the walls in the latter were
      significantly enriched in hexosamine, but had a reduced content in phosphate and
      amino acid. In both strains, the cell walls limited their sensitivity to this
      antifungal agent. The absence of cell wall increased the sensitivity of the cells
      to this polyene by 5 to 10-fold. When the cells were treated with enzymes such as
      pronase and chitinase in order to change the cell wall structure just before
      inoculation, the yeasts appeared more resistant to the antibiotic. However,
      treatments with chymopapain and phospholipase C did not significantly change the
      sensitivity of the two strains to this agent. Cells treated with acid phosphatase
      displayed a longer lag phase than the control cells. In addition, when cultured
      in the presence of AmB, the cells were less sensitive to this agent. The present
      results reveal that both a change in the ionic charges of the cell wall and an
      alteration in the cell wall structure modified the sensitivity of these yeast
      strains to AmB.

PMID- 9766215
TI  - Computer identification of Escherichia coli rRNA gene restriction patterns.
AB  - A total of 191 strains of Escherichia coli comprising 164 serovar reference
      strains and 28 clinical strains were characterized by rRNA gene restriction
      patterns (ribotypes) generated after cleavage of total DNA with MluI, ClaI or
      HindIII restriction endonucleases and hybridization of fragments with
      acetylaminofluorene-labelled 16 + 23S rRNA. A wide diversity of ribotypes was
      observed with endonucleases MluI (104 patterns), ClaI (90 patterns) and HindIII
      (98 patterns). When MluI was used, 85% of patterns (11 to 15 fragments) shared
      five fragments 17.09, 3.94, 3.06, 2.23 and 1.76 kb in size. When these fragments
      were used as internal standards, the percent errors in fragment length
      determination was half of that obtained with an external standard. Two fragment
      size databases of MluI and ClaI ribotypes were built. Automatic identification
      was obtained after setting the percent fragment size variation tolerance (error)
      at 5%. MluI ribotyping is recommended as a primary epidemiological marker.
      Strains with similar MluI ribotype should then be submitted to ClaI ribotyping.
      Ribotyping with HindIII can only be the third choice, since the patterns were
      often uncertain due to the frequent occurrence of faint bands. Most of the
      studied serovars gave discrete patterns and these data provide the basis for a
      molecular typing system for E. coli which could possibly substitute for
      serotyping when the latter is not available.

PMID- 9766216
TI  - Typing of nosocomial strains of Serratia marcescens: comparison of pulsed-field
      gel electrophoresis of macrorestriction fragments with biotyping, esterase typing
      and ribotyping.
AB  - Fifty nosocomial isolates of Serratia marcescens, collected in six Belgian
      hospitals between 1986 and 1990, were characterized by using pulsed-field gel
      electrophoresis (PFGE) with XbaI. The results were compared with those previously
      obtained by three other methods: biotyping, esterase electrophoresis typing and
      ribotyping with EcoRI and HindIII. Macrorestriction analysis (42 PFGE groups) and
      esterase typing (42 zymotypes) proved to be the most discriminating, followed by
      ribotyping (28 ribotypes) and biotyping (10 biochemical profiles). Biotyping
      would serve as a screen to identify isolates, due to its accessibility. Esterase
      typing provided a reliable tool to make subdivisions within biotypes because of
      congruence between biochemical groups and esterase patterns. Additional
      discrimination was still achieved by ribotyping and PFGE. It is concluded that
      the combined results of these four markers were useful for distinguishing all
      epidemic and sporadic isolates.

PMID- 9766217
TI  - PCR-based detection of verotoxin-producing Escherichia coli (VTEC) in ground
      beef.
AB  - Pathogenic strains of Escherichia coli producing verotoxins (VTs) have been
      recognized as a cause of human disease, and rapid and sensitive detection tests
      are urgently needed to ensure the safety of food, especially ground beef. We
      applied two nested polymerase chain reaction (PCR) assays to detect the genes
      encoding VT1 and VT2 irrespective of the bacterial serotype. In combination with
      a direct sample preparation protocol, we were able to uncover the presence of
      about 110 CFU of verotoxinogenic E. coli (VTEC) in 10 g of ground beef. When a
      six-hour enrichment was included, we found the detection limit to be in the range
      of 1 to 10 bacterial cells per 10 g of ground beef. To evaluate our detection
      system, we tested 30 ground beef samples originating from butcher shops in Berne,
      Switzerland. One sample yielded positive PCR results for both the VT1 and VT2
      genes, indicating the presence of verotoxinogenic E. coli. Finally, 20 food
      homogenates, shown to contain E. coli strains by standard culture, were analysed
      with our method, and the gene encoding VT2 was detected in one cheese sample. The
      results suggest that the described PCR method can serve as a valuable tool for
      the surveillance of VTEC contamination of foods.

PMID- 9766218
TI  - Protein and peptide secretion by ABC exporters.

PMID- 9766219
TI  - Growth dependence of alpha-glucan phosphorylase activity in Thermus thermophilus.
AB  - Glycogen from the thermophilic eubacterium Thermus thermophilus has been
      characterized by enzymatic, chemical and spectroscopic analysis. With an average
      chain length of seven glucose units, the glycogen from T. thermophilus is one of
      the most highly branched glycogens known. In contrast to other bacterial species,
      in T. thermophilus, accumulation of glycogen appears not be affected by low
      nitrogen concentration. For the first time, alpha-glucan phosphorylase activity
      and glycogen content were measured throughout the growth cycle of T. thermophilus
      in order to gain insight into glycogen metabolism. In contrast to the situation
      that prevails in Escherichia coli, additional carbon sources had no effect on
      alpha-glucan phosphorylase activity in T. thermophilus. Maximal activity of the
      thermophilic enzyme was found in the early logarithmic phase of growth,
      suggesting a function of the alpha-glucan phosphorylase in T. thermophilus as an
      outgrowth-specific enzyme.

PMID- 9766220
TI  - Cloning and sequence determination of a phi AAU2 gene whose product aborts the
      phage lytic cycle.
AB  - This communication describes the cloning of a 1.8-kb fragment from the genome of
      the corynephage phi AAU2, which aborts the phage lytic cycle when cloned on a
      high-copy shuttle vector. The associated phenotype, called Apld (aborting phage
      lytic development), was revealed by noting the reduced plaque size and lower
      efficiencies of plaquing of phi AAU2 cp, a virulent derivative of phi AAU2, on
      "Arthrobacter aureus"-C70 Apld+ cells. Adsorption and phage DNA transfection
      experiments showed evidence that Apld acted once the phage DNA had entered into
      the cell; apld was confined to a single open reading frame (ORF), encoding a
      putative 63-aa polypeptide which did not show any homology to proteins contained
      in the databanks; apld is followed by an ORF the product of which shows homology
      with a protein expressed by the early region of the Streptomyces phage phi C31.

PMID- 9766221
TI  - Two iron-regulated putative ferric siderophore receptor genes in Bordetella
      bronchiseptica and Bordetella pertussis.
AB  - Two iron-regulated genes with deduced homology to TonB-dependent ferric
      siderophore receptors were cloned from Bordetella bronchiseptica by screening a
      library of TnphoA insertion mutants. bfrB and bfrC were iron-repressed in B.
      bronchiseptica by a Fur-dependent mechanism, and were expressed from promoters
      overlapped by potential Fur-binding sites. Both genes were highly conserved among
      Bordetella species and were also iron-regulated in Bordetella pertussis. bfrB and
      bfrC mutants of both species and a bfrB-bfrC double mutant of B. bronchiseptica
      had no discernible defects in utilization of known iron sources for Bordetella.

PMID- 9766222
TI  - Replication of the linear chromosomal DNA from the centrally located oriC of
      Streptomyces ambofaciens revealed by PFGE gene dosage analysis.
AB  - From a cosmid clone of Streptomyces ambofaciens containing the dnaA and gyrAB
      genes, a 2.7-kb self-replicating DNA fragment containing the chromosome
      replication origin oriC was isolated. This cosmid was previously maped physically
      to a region near the middle of the 8-Mb linear chromosomal DNA. A pulsed-field
      gel electrophoresis time-course analysis revealed that sequences flanking oriC
      were overrepresented relative to the rest of the chromosomal DNA during rapid
      growth, indicating that this origin is active. In addition, the terminal regions
      of the chromosomal DNA showed a slight overrepresentation at the onset of
      stationary phase.

PMID- 9766223
TI  - Carnitine acts as a compatible solute in Brevibacterium linens.
AB  - Carnitine is a trimethyl amino acid found at relatively high concentrations in
      materials of animal origin. Exogenously provided L-carnitine was found to
      stimulate growth of Brevibacterium linens ATCC 19391 in media with inhibitory
      osmotic strength. Its osmoprotective ability was as potent as that of glycine
      betaine. Electrophoretic and spectroscopic (NMR) analysis showed that this
      compound is only transiently accumulated, but in significant amounts, by B.
      linens under hyperosmotic stress and is converted into glycine betaine. The L
      carnitine/glycine betaine pathway is inducible by L-carnitine in B. linens. The D
      enantiomer did not improve growth of B. linens, even though this solute is
      accumulated by B. linens at the same level as glycine betaine. The two isomeric
      forms of carnitine repress the build-up of ectoine, the main endogenous osmolyte
      in B. linens.

PMID- 9766224
TI  - AFLP typing of Staphylococcus epidermidis in multiple sequential blood cultures.
AB  - AFLP is a novel high-resolution PCR-based DNA fingerprinting method generating
      complex banding patterns that can be used for comparative analysis. In the
      present study, the applicability of AFLP in fingerprinting Staphylococcus
      epidermidis isolates was investigated. The criteria considered were stability of
      patterns, reproducibility, discriminatory capacity and consistency with
      epidemiological context. Repeated testing of strains and investigation of
      subcultures showed that AFLP patterns were reproducible and stable with an
      intrastrain similarity of S > or = 94% as determined by analysis of digitized
      patterns. Fifteen unrelated strains were heterogeneous, with a level ranging from
      78-93%. The applicability of AFLP in epidemiological studies of S. epidermidis
      was tested on 11 sets of four blood isolates each, from 11 patients with
      suspected septicaemia. Nine sets had indistinguishable or highly similar AFLP
      patterns for each isolate per set, while two sets had heterogeneous patterns.
      These results show that AFLP has high discriminatory power for strain
      identification in S. epidermidis.

PMID- 9766225
TI  - Homologues of helicase genes priA and ruvAB of Borrelia burgdorferi, the Lyme
      borreliosis agent.
AB  - A DNA library of strain HB19 from Borrelia burgdorferi sensu stricto, an agent of
      Lyme borreliosis, was constructed in the cosmid pLA2917. Genes involved in
      initiation of DNA replication and resolution of recombination intermediates
      (Holliday junctions) were found on a 23-kbp region up to 0.7 kbp of the "left"
      extremity of the linear chromosome in representative species of B. burgdorferi
      sensu lato. The potential ruvB gene, located at 22 kbp from the left telomere,
      was identified by the similarity of its deduced amino acid sequence to RuvB
      (helicases) of other bacteria. B. burgdorferi ruvB is part of an operon which
      comprises the homologues of ruvA, queA and pfbB. Expression of the B. burgdorferi
      ruvB and ruvA genes renders a wild-type Escherichia coli sensitive to UV light
      and mitomycin, indicative of negative complementation. priA, which encodes the
      potential recognition factor for the primosome assembly site, was found at 15 kbp
      from the left telomere. RuvB and PriA sequences have motifs characteristic of
      helicases: a DExH box and an ATP binding site.

PMID- 9766226
TI  - Characterization of the Lactobacillus helveticus groESL operon.
AB  - This study utilized inverse polymerase chain reactions to characterize a 2.7-kb
      region of the Lactobacillus helveticus LH212 chromosome that included two
      complete and one truncated open reading frames (ORFs). Protein homology searches
      showed that the first two ORFs encoded homologs to the universally conserved heat
      shock proteins GroES and GroEL. Amino acids encoded by the 5' end of the
      truncated ORF that was downstream of groEL showed good homology to the amino
      terminal end of the Streptococcus pneumoniae DNA mismatch repair enzyme HexA.
      Nucleotide sequence analysis identified a putative transcriptional promoter
      upstream of groES that was comprised of -35 and -10 hexamers flanked upstream and
      downstream by copies of the conserved Gram-positive heat shock gene regulatory
      sequence, CIRCE. A large inverted repeat that may function as a rho-independent
      transcriptional terminator was located between groEL and the third ORF. Northern
      hybridization of an LH212 groEL gene fragment to RNA isolated from cells that had
      been heat shocked at 52 degrees C for 0, 5, 10 or 15 min detected a 2.2-kb
      transcript in each of the cell preparations. Densitometry showed the
      concentration of this mRNA species was approximately 4-fold higher after heat
      shock for 5 or 10 min and 3-fold higher after 15 min of heat shock.

PMID- 9766227
TI  - The 16-kDa alpha-crystallin-like protein of Mycobacterium bovis BCG is produced
      under conditions of oxygen deficiency and is associated with ribosomes.
AB  - A 16-kDa protein, identical to the alpha-crystallin-like stress protein, was
      induced under O2-deficient culture conditions and bound principally to the 30S
      ribosomal subunits of Mycobacterium bovis BCG substrain Tokyo (BCG). The 16-kDa
      protein was shown to be tightly associated with the ribosome.

PMID- 9766228
TI  - Identification and molecular cloning of a novel secretion antigen from
      Mycobacterium tuberculosis and Mycobacterium bovis BCG.
AB  - A novel protein called SA-5K was identified in Mycobacterium bovis BCG (BCG)
      short-term culture filtrates (CFs) by means of a recently described monoclonal
      antibody (mAb), L8D8. This protein had an apparent molecular mass (MM) of 5 kDa,
      as judged by Western blotting after sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis in reducing conditions, and did not seem to contain any sugar or
      lipid substituents. In the present work, SA-5K was purified from BCG CFs by
      affinity chromatography. A protein that could be detected in Western blot but not
      by standard protein staining techniques was obtained. When SA-5K was subjected to
      aminoterminal sequencing, the 10 amino acids (aa) found matched the first 10-aa
      sequence deduced from an open reading frame (ORF) of M. tuberculosis. The ORF
      encodes a polypeptide, likely to include a signal for secretion, with an
      estimated MM of 8.3 kDa after signal peptide cleavage. The secretory nature of SA
      5K was confirmed by the fact that it could only be detected in CFs, but not in
      other BCG subcellular fractions. After size exclusion chromatography, reactivity
      with mAb L8D8 was found to peak in the 45-50- and 14-16-kDa fractions. The latter
      MM was close to that estimated from the ORF of M. tuberculosis, implying that the
      5-kDa antigen detected initially by Western blot in reducing conditions was a
      portion of SA-5K released after reduction of a disulphide bridge. The presence of
      the gene for SA-5K in BCG and its identity were confirmed by PCR (polymerase
      chain reaction) with specific primers and restriction analysis: the PCR product
      was slightly shorter in BCG than in M. tuberculosis. The gene coding for SA-5K
      was cloned by PCR from BCG and M. tuberculosis DNA and was expressed in
      Escherichia coli.

PMID- 9766230
TI  - Chitinolytic activity at low temperature of an Antarctic strain (A3) of
      Verticillium lecanii.
AB  - The chitinolytic activity of Verticillium cfr. lecanii A3, a strain isolated from
      continental Antarctica, was compared to those of two selected strains of
      Trichoderma harzianum. After 72 h of incubation at 25 degrees C in media
      containing chitin as the sole carbon source, all strains showed the same enzyme
      activity (ca. 230 mU/ml); at 15 degrees C, the levels of enzyme activity of the
      three strains were similar to those obtained at 25 degrees C. At 5 degrees C, in
      contrast, the activity of V. lecanii was ca. 4 times higher than those of both
      strains of T. harzianum (203 and 57 mU/ml, respectively; incubation time 144 h).
      The chitinase of V. lecanii, purified by preparative isoelectric focusing and ion
      exchange chromatography, was shown to be a glycoprotein with apparent molecular
      weight of 45 kDa and isoelectric point of 4.9. The enzyme was active over a broad
      range of temperatures (5-60 degrees C): at 5 degrees C, its relative activity was
      still 50% of that recorded at 40 degrees C (optimal temperature). V. lecanii and
      its purified chitinase showed clear inhibitory effects on the growth of some test
      moulds such as Mucor plumbeus, Cladosporium cladosporioides, Aspergillus
      versicolor and Penicillium verrucosum: observations under the light and scanning
      electron microscopes revealed that growth inhibition was accompanied by mycelial
      damage and cell lysis.

PMID- 9766229
TI  - Biomineralization of carbonates by Halomonas eurihalina in solid and liquid media
      with different salinities: crystal formation sequence.
AB  - Carbonate precipitation by 20 strains of the moderately halophilic species
      Halomonas eurihalina in both solid and liquid media was studied. The influence of
      salinity and temperature on the quantity and type of crystals precipitated was
      also investigated. Some strains of H. eurihalina formed crystals in all
      conditions tested. The mineral phases precipitated were magnesium calcite,
      aragonite and monohydrocalcite in variable proportions depending on various
      factors such as the type of growth medium employed and its salinity. Scanning
      electron microscopy and X-ray dispersive energy microanalysis were used to
      investigate the crystal formation sequence. The process of biolith formation was
      sequential. It started with chains or filaments of bacteria, giving way to discs
      which finally produced spherical forms of approximately 50 microns in diameter.
      We suggest a mechanism of carbonate crystal formation by H. eurihalina.

PMID- 9766231
TI  - Inhibition of Salmonella intracellular proliferation by non-phagocytic eucaryotic
      cells.
AB  - Salmonella typhimurium is an intracellular pathogen capable of proliferating
      within vacuolar compartments of non-phagocytic eucaryotic cells. This process has
      been shown to be essential for virulence in the mouse typhoid model (Leung and
      Finlay, Proc. Natl. Acad. Sci. USA, 88, 11470-11474, 1990). Here we present
      evidence that certain non-phagocytic eucaryotic cell lines, such as 3T3 (mouse
      fibroblasts) and NRK (rat fibroblasts) cells, are not permissive for S.
      typhimurium intracellular proliferation. Moreover, viability of intracellular
      bacteria residing within both cell types notably decreases at late postinfection
      times (72 h). These results clearly demonstrate that non-phagocytic eucaryotic
      cells are capable of destroying intracellular S. typhimurium. Experimentation
      with 3T3 and NRK cell lines might provide an appropriate in vitro model for
      identifying new bacterial and/or eucaryotic factors regulating Salmonella
      intracellular proliferation within vacuoles of the host eucaryotic cell.

PMID- 9766232
TI  - Regulation of the expression of a gene encoding beta-endoglucanase secreted by
      Myxococcus xanthus during growth: role of genes involved in developmental
      regulation.
AB  - An endoglucanase, CelA, is secreted by Myxococcus xanthus only during exponential
      growth. The production of this enzyme is decreased by mutations in 5 different
      genes (Exc +/- phenotype), three of which correspond to asg genes which regulate
      the production of an early cell-to-cell signal in development. Transcription of
      celA is decreased in two of these Exc +/- mutants, whereas a post-transcriptional
      step is affected in two other Exc- mutants. Thus, asg genes, in addition to
      regulating the onset of development, also regulate a gene (celA) that is
      expressed during exponential growth and that is not involved in development.

PMID- 9766234
TI  - Characterization of catechol- and chlorocatechol-degrading activity in the ortho
      chlorinated benzoic acid-degrading Pseudomonas sp. CPE2 strain.
AB  - Pyrocatechase activity was studied in the Pseudomonas sp. CPE2 strain, which is
      capable of growing on 2-chlorobenzoic and 2,5-dichlorobenzoic acid, giving rise
      to catechol and 4-chlorocatechol, respectively, as intermediate metabolites. The
      CPE2 crude extract was found to metabolize both catechol and 4-chlorocatechol.
      Enzymatic as well as phenotypic studies performed both on this strain and on a
      mutant strain lacking the chlorocatechol-degrading genes were consistent with the
      presence of two catechol-cleaving enzymes, one active mainly against catechol
      (pyrocatechase I) and the other with broader substrate specificity (pyrocatechase
      II). The latter enzyme also appeared to be induced when CPE2 cells were grown on
      2-chlorobenzoic acid, thus contributing to catechol metabolism, in addition to
      pyrocatechase I. Despite the presence of a large plasmid in CPE2 cells, the
      chlorocatechol-degrading genes, highly homologous to the clc operon, were located
      on the chromosome. The selection at relatively high frequency of mutant strains
      with altered growth capabilities and which lacked the chlorocatechol-degrading
      genes suggests a transposon-like character for these catabolic genes in the CPE2
      strain.

PMID- 9766233
TI  - Reaggregation and binding of cell wall proteins from Candida albicans to
      structural polysaccharides.
AB  - Urea or hot sodium dodecyl sulphate extracted a significant amount of the same
      proteins from the matrix of the cell wall of the yeast form and mycelial cells of
      Candida albicans. Gel filtration analysis of the urea-extracted proteins revealed
      that they occurred in the form of large complexes which were unaffected by up to
      8 M urea. Among them, proteins en route to becoming covalently associated within
      the wall scaffold were identified by their reaction with specific antibodies.
      When urea was removed by dialysis, some of these proteins specifically
      reassociated into large aggregates which bound strongly with ConA, whereas others
      remained soluble in smaller associated products. The ability of some of these
      proteins to bind to the insoluble wall polysaccharides was also assessed. No self
      assembling proteins were able to bind to glucans and/or chitin. Specificity of
      the binding to polysaccharides made of beta-bound glucosyl or N
      acetylglucosaminyl residues was determined by the competitive effect of several
      disaccharides. Whereas laminaribiose and diacetylchitobiose were strong
      inhibitors of protein binding to both glucan and chitin, lactose, maltose and
      sucrose were ineffective.

PMID- 9766235
TI  - Combined numerical analysis based on the molecular description of Mycobacterium
      tuberculosis by four repetitive sequence-based DNA typing systems.
AB  - Mycobacterium tuberculosis clinical isolates (113 isolates from 78 patients) were
      typed using IS6110-RFLP, DR-RFLP, DR-based spoligotyping and direct repetitive
      element PCR (DRE-PCR). The similarities among isolates were compared for each
      individual method. The individual matrix distance files for each method were
      summed and averaged, and the resulting unique distance file was analysed by the
      UPGMA (unweighted pair group method with arithmetic averages). Combined numerical
      analysis with 3 genetic markers (IS6110-RFLP, DR-RFLP and spoligotyping) was
      performed for all 78 clinical isolates, whereas analysis with 4 genetic markers
      (with the addition of DRE-PCR) was performed on the 10 main clusters described.
      When compared to molecular analysis based on individual markers, the molecular
      description based on multiple genetic markers enabled comparison of the results
      obtained by individual methods and the obtaining of a more accurate view of
      strain identity and clusters comparison. The resulting cumulative dendrogram was
      more accurate for studying the population structure of M. tuberculosis and may be
      a good tool for elucidating intraspecies genetic microevolution.

PMID- 9766237
TI  - Cooperation between the components of the meningococcal transferrin receptor,
      TbpA and TbpB, in the uptake of transferrin iron by the 37-kDa ferric-binding
      protein (FbpA).
AB  - Meningococcal TbpAB complexes TbpA, TbpB and FbpA were purified and used to study
      their role in the uptake of iron from transferrin to FbpA. Purification was
      achieved by affinity chromatography techniques, yielding homogeneous, non
      denatured and functional material. TbpA could not be separated from TbpB and had
      to be purified from a TbpB-defective mutant strain. FbpA was able to bind iron
      from transferrin only when TbpAB complexes, TbpA and/or TbpB, were also present
      during the interaction. The highest uptake efficiences were obtained with TbpAB
      complexes or TbpA/TbpB mixtures. We conclude that the TbpA and TbpB molecules
      form true functional transferrin receptors, that FbpA is able to take iron
      directly from transferrin when in the presence of the components of the receptor,
      and that both Tbps are necessary for an optimal operation of the uptake system.

PMID- 9766236
TI  - Stable electrotransformation of symbiont candidate diazotrophic bacterium with
      plasmids carrying selectable and screenable marker genes.
AB  - Nitrogen-fixing symbioses had been established between the originally asymbiotic
      soil bacterium Azotobacter vinelandii CCM289 and different lower and higher plant
      species. Better characterization and further development of such artificial
      systems require a reliable genetic transformation method for the introduction of
      marker genes into symbiont candidates. The performance of electroporation was
      evaluated using pJB3 (4.8 kb), pBI121 (12.8 kb) and pFAJ31.2 (24 kb) plasmid DNAs
      containing selectable (Ap, Km, Tc) and screenable (gusA, lacZ) marker genes. The
      adapted methods for the preparation of transformation-competent azotobacters and
      their electroporation (18 kV/cm electric field strength, 5 ms time constant, 0
      degree C) provided up to 6.8 x 10(5) transformants per microgram plasmid DNA,
      which is about 10(3) times the transformation efficiency achieved in control
      experiments. No electrotransformants were obtained with the 24-kb pFAJ31.2. The
      size of plasmid DNA did not significantly affect the efficiency of
      transformation. Transformants were able to grow at antibiotic concentrations that
      were 100-200 times greater than the lowest amounts that completely inhibited the
      growth of wild-type bacteria. A constitutive expression of gusA gene was observed
      in transformants with the CaMV 35S promoter-gusA fusion containing pBI121, while
      lacZ expression was not detected under the control of the lac promoter in pJB3
      transformants. Electroporated plasmids were reisolated from transformants in
      their original form, while non-transformed bacteria did not contain indigenous
      plasmids. PCR amplification and Southern DNA blot hybridization showed the
      integration of plasmid DNA into the host genome as well. Transformants retained
      their nitrogen-fixing ability and had normal morphological and growth
      characteristics. Experimental findings proved the stable maintenance of plasmid
      DNA in azotobacters, making possible the routine transformation and detection of
      these symbiont candidates.

PMID- 9766238
TI  - Biochemical characterization of tellurite-reducing activities of Bacillus
      stearothermophilus V.
AB  - Bacillus stearothermophilus V is a naturally occurring Gram-positive rod which
      exhibits resistance to potassium tellurite. Crude extracts of this bacterium
      catalyse the NADH-dependent, protease-sensitive reduction of K2TeO3 in vitro. Two
      fractions which showed the ability to reduce potassium tellurite (H1 and H2) were
      obtained. Fraction H1 behaved as a macroaggregate exhibiting a very high
      molecular mass that could not be estimated accurately. Upon electrophoresis in
      polyacrylamide gels in the presence of SDS, however, it was resolved into three
      distinct bands of 60, 41 and 37.5 kDa. On the other hand, an M(r) of 121 was
      determined for fraction H2 by means of gel filtration and high-pressure liquid
      chromatography. In SDS-PAGE a unique protein band of 60 kDa was observed,
      suggesting that it is actually a dimer. Both fractions showed pH and temperature
      optima of 7.5 and 57 degrees C, respectively. Concentrations of 2.5 M NaCl or
      0.35 mM SDS inhibited fraction H2 almost completely, while fraction H1 retained
      20% of its activity under the same conditions. Concentrations of 5 mM EDTA caused
      the activity of both fractions to increase 2-fold. In addition to reducing
      tellurite, they were also able to reduce Na2SeO3 and Na2SO3 in vitro.

PMID- 9766239
TI  - Biodegradation of phenol and p-cresol by the hyphomycete Scedosporium
      apiospermum.
AB  - A hyphomycete with the ability to utilize phenol and p-cresol as carbon and
      energy source was isolated from soil and subsequently identified as Scedesporium
      apiospermum. The identification of degradation metabolites and the detection of
      the corresponding catabolic enzymes in crude extracts enabled us to propose
      different pathways for the degradation of both phenol and p-cresol in this
      organism. Generally, the catabolism proceeded via three different dihydroxylated
      intermediates (catechol, hydroxyhydroquinone and protocatechuate) which were
      intradiolically cleaved by the corresponding inducible dioxygenases and further
      catabolized via the 3-oxoadipate pathway.

PMID- 9766240
TI  - Mesophilic Aeromonas strains from different serogroups: the influence of growth
      temperature and osmolarity on lipopolysaccharide and virulence.
AB  - Growth of mesophilic Aeromonas sp. strains from serogroups O:13, O:33 and O:44 at
      different temperatures and osmolarity resulted in changes in the
      lipopolysaccharide (LPS) and virulence of the strains tested, as we had
      previously reported for strains from serogroup O:34. The effect of osmolarity
      could be observed when the cells grew at 37 degrees C but not at 20 degrees C.
      Purified LPS from cells cultivated at 20 degrees C (high or low osmolarity) or at
      37 degrees C at high osmolarity was smooth, whereas the LPS extracted from the
      cells cultivated on low osmolarity was rough. The smooth strains were resistant
      to the bactericidal activity of non-immune serum, while the rough strains were
      sensitive and showed better adhesion to Hep-2 cells than the rough strains.
      Furthermore, the smooth strains were more virulent for fish and mice than the
      rough strains. For mesophilic Aeromonas sp. strains from serogroups O:1 to O:44,
      these changes were not observed, except for serogroups O:13, O:33, O:34 and O:44.

PMID- 9766241
TI  - Cellulolytic enzymes of rumen anaerobic fungi Orpinomyces joyonii and Caecomyces
      communis.
AB  - The rumen anaerobic fungi Orpinomyces joyonii A4 and Caecomyces communis JB1 were
      grown on microcrystalline cellulose (MC) and alfalfa hay. The cellular
      distribution of cellulases produced by these organisms was monitored. Fungal
      cultures were separated into extracellular, intracellular and cell wall fractions
      and assayed for endoglucanase (EG) and beta-glucosidase activity. In both fungal
      isolates, EG activity was the highest in the extracellular fraction regardless of
      the substrate used. The beta-glucosidase activity produced by O. joyonii was
      mainly found in the cell wall fraction. On the contrary, the same enzyme activity
      in C. communis predominated in the extracellular fraction. The polycentric
      isolate A4 more efficiently utilized both substrates, produced more short chain
      fatty acids (up to 31 mmol/l) and showed higher total levels of EG (2744 nmol
      glucose/h/ml) than the monocentric strain JB1. On the other hand, beta
      glucosidase (9033 nmol glucose/h/ml) activity was the highest in cultures of C.
      communis grown on cellulose. In cultures of O. joyonii grown on MC, the
      production of yellow affinity substance (YAS) with similar properties compared
      with yellow substance from Clostridium thermocellum was observed. This compound
      increased the adsorption of fungal cellulases to MC the temperature and pH range
      tested.

PMID- 9766242
TI  - Endemic presence of Salmonella bongori 48:z35:- causing enteritis in children in
      Sicily.

PMID- 9766243
TI  - 16S-23S and 23S-5S intergenic spacer regions of lactobacilli: nucleotide
      sequence, secondary structure and comparative analysis.
AB  - Lactobacilli have been used as industrial starters for a long time, but in
      several cases their identification was, and still is, neither easy nor reliable.
      The aim of the present work was to examine whether the intergenic spacer regions
      could be of value in the identification of Lactobacillus species. For that
      purpose, the polymerase chain reaction (PCR) was used to amplify 16S-23S and 23S
      5S spacer regions of Lactobacillus (L.) acidophilus, L. delbrueckii subsp.
      bulgaricus, L. casei, L. helveticus and L. curvatus. The PCR products were
      directly sequenced, and two forms of ribosomal RNA (rrn) operons were identified
      in each species studied: one with tandem tRNA(Ile)/tRNA(Ala) genes and the other
      one without tRNA genes. Our study revealed that the rrn operons of Lactobacillus
      species studied comprise the genes of 16S, 23S and 5S rRNA, in that order. Only
      the tRNA genes and the rRNA processing stems are highly conserved in spacer
      regions of lactobacilli. The divergence between the lactobacilli spacer region
      sequences arises from insertions and deletions of short sequences. These
      sequences could be interesting candidates for the development of species-specific
      probes. Theoretical RNA/RNA secondary structure models of the interaction between
      the two spacer region sequences were constructed. In conclusion, the two spacer
      region sequences may prove to be a useful alternative to 16S and 23S rDNA
      sequencing for designing species-specific probes and for establishing
      phylogenetic relationships between closely related species such as L. curvatus
      and L. casei or L. acidophilus and L. helveticus.

PMID- 9766244
TI  - Transdermal permeation of neutral molecules by skin electroporation.
AB  - Electroporation of skin has recently been shown to enhance transport of charged
      molecules across skin by up to four orders of magnitude. This study demonstrates
      that high-voltage pulses can also increase transdermal permeation of two neutral
      model solutes, i.e. mannitol and water, up to 100-fold. The elevated flux results
      from the persistent increase in skin permeability following electroporation,
      rather than from electro-osmosis during pulsing. Control on transport was
      achieved by controlling the electrical parameters of the pulse, i.e. the pulse
      voltage, time constant and number.

PMID- 9766245
TI  - Kinetics of release of a model disperse dye from supersaturated cellulose acetate
      matrices.
AB  - A study has been made of the kinetics of release into water of a model disperse
      dye (4-aminoazobenzene) from supersaturated solvent-cast cellulose acetate films
      at room temperature. Excess dye was introduced into the polymer matrix by: (i)
      sorption from aqueous solution at 100 degrees C; (ii) sorption from the vapour
      phase at 110 degrees C; or (iii) prior dissolution in the casting solvent. The
      effect of the method of introduction of the dye, the degree of supersaturation
      and the rate of agitation of the bath were investigated. Under conditions of
      strong agitation, the release kinetics from films dyed by method (i) or (iii)
      were in general accord with the theoretical model which assumes solute in the
      film in excess of the saturation limit to be in the form of immobile aggregates
      at equilibrium with mobile dye; although the value of the diffusion coefficient
      of the solute in the film was found to be substantially higher than that in the
      unsaturated film. On the other hand, when dyeing had been effected from the
      vapour phase, Fickian kinetics was followed and the diffusion coefficient was
      found to be equal to that observed in unsaturated film. It was concluded that
      under these conditions, the excess dye in the film tends to remain molecularly
      dispersed. Under conditions of slow agitation, the square root of t kinetics was
      not attained in many instances. General and early-time approximate expressions
      based on the Roseman-Higuchi model proved useful for the interpretation of the
      results in such cases; while the said model was extended to include the effect of
      significant variation of the partition coefficient of the solute with
      concentration.

PMID- 9766246
TI  - Transdermal alniditan delivery by skin electroporation.
AB  - The aim of this study was to evaluate the transdermal permeation of alniditan by
      electroporation and to compare with iontophoretic delivery. The influence of the
      electrical parameters of electroporation was investigated in vitro using a
      factorial design study. The transdermal flux of alniditan was enhanced by two
      orders of magnitude by application of high voltage electrical pulses. The
      electrical parameters of electroporation-i.e. the voltage, the duration and the
      number of pulses-allowed a control of drug permeation. Both transport during and
      after pulsing were shown to be important for alniditan transdermal delivery by
      electroporation. Electroporation was found more efficient in promoting alniditan
      permeation than an iontophoresis transferring the same amount of charges.

PMID- 9766247
TI  - Methoxy-polyethoxy side-chain silastomers as materials controlling drug delivery
      by diffusion flux.
AB  - The density of a diffusion medium and the solubility of the diffusant in this
      material are predominant parameters which control the diffusion flux. Side-chain
      silastomers can be structurally modified in such a manner that density and
      polarity are widely varied and adjustable to distinct conditions. The synthesis
      of cross-linked methoxy-polyethoxy side-chain polysiloxanes is performed by
      reaction of alpha, omega-bis-(trimethyl-silyloxy)-poly-(methyl-hydrogen
      siloxane), alpha, omega-divinyl-poly-(dimethyl-siloxane), and 4-propenyloxy-(4'
      methoxy-polyethoxy)-biphenyl. Silastomer foils were obtained with side-chains
      having up to 9 ethoxy groups. Various silastomer types were characterized by DSC
      measurements, polarization microscopy, uptake of water and salicylic acid (as
      model drug), and by permeation measurements. The polarity of the polymers depends
      on their contents of ethoxy groups influencing the uptake of polar substances.
      Polymers with penta-ethoxy and hepta-ethoxy groups at the side-chains take up
      water under swelling. The solubility and the distribution coefficients of
      salicylic acid are linearly correlated to the weight fractions of the methoxy
      polyethoxy groups in all silastomer types. The temperature dependence of the
      distribution coefficients of the penta-ethoxy and hepta-ethoxy polymer types
      shows deviations from the Arrhenius equation. As the side-chains occupy
      considerable volumes, the density of the molecular packing within the cross
      linked polysiloxane matrices is high. The arrangement of the side-chain domains,
      therefore, depends on the chain length of the cross-linker; the diffusion
      coefficients are influenced by this parameter. Evidence for the existence of a
      lyotropic liquid-crystalline phase was observed for one type of these polymers
      only. Methoxy-polyethoxy side-chain silastomers as membranes or matrices are
      suited for controlled drug delivery. Drug liberation rates and swelling by uptake
      of water can be widely altered by variations of the side-chain structures.

PMID- 9766248
TI  - Degradation and release profile of microcapsules made of poly[L-lactic acid-co-L
      lysine(Z)].
AB  - Poly(L-lactic acid-co-L-lysine(Z)) with different Lys(Z) contents was synthesized
      by Sn(II) salt-catalyzed ring-opening copolymerization of 3(S)
      benzyloxycarbonylaminobutyl-6(S)-methylmorpholine-2,5-dione with lactide.
      Microcapsules of the copolymers were prepared by solvent evaporation from w/o/w
      emulsion, and FITC-dextran release from the microcapsules was investigated. The
      FITC-dextran release was dependent on the composition and molecular weight of the
      copolymers. The release from the microcapsules containing Lys(Z) of 6.5 mol% was
      slowest among the present microcapsules, which is due to smooth surface and very
      small microcapsules included in a large microcapsule. On the other hand, the
      release from microcapsules containing Lys(Z) of 31 or 50 mol% became faster after
      several days of incubation. GPC measurement of the microcapsules revealed that
      the copolymers were degraded during the incubation. Cracks and pores were formed
      on the microcapsule wall. PLLA microcapsules having comparable molecular weight
      to the copolymers showed neither release acceleration nor degradation in short
      time incubation. Therefore, the introduction of Lys(Z) units made PLLA
      susceptible to degradation to result in delayed acceleration of release.

PMID- 9766249
TI  - Development and evaluation on transdermal delivery of enoxacin via chemical
      enhancers and physical iontophoresis.
AB  - Iontophoresis and enhancers were performed to enhance percutaneous absorption of
      enoxacin so as to compare the enhancement between these two enhancing methods.
      The cationic surfactant of benzalkonium chloride showed the highest enhancing
      activity for enoxacin for all pH values of buffer vehicles. The enhancement
      factor of sodium laurylsulfate showed a dose-dependent property between the range
      of 0.1% to 3.0% concentration. Nonionic surfactant of Polysorbate 80 did not
      exhibit any enhancing effect on the percutaneous absorption of enoxacin. The
      highest enhancement factor of iontophoretic delivery was observed at pH 5.0
      solution of anodal iontophoresis for cationic enoxacin. The cathodal
      iontophoresis of negative molecules and anodal iontophoresis of neutral molecules
      showed lower enhancing effect for enoxacin. The fact that the skin residuals of
      enoxacin after iontophoresis showed both tremendous and current density-dependent
      amounts for cationic enoxacin suggested local skin and soft tissue infections
      might be treated by this physical enhancement method. Combination of benzalkonium
      chloride and iontophoresis exerted a synergistic effect for anionic enoxacin in
      pH 10.0, which was possibly due to the shielding of negative charge in skin and
      the water molecules carried by chloride.

PMID- 9766250
TI  - Absorption/release of polyvalent metal ions by a polyelectrolyte gel.
AB  - The swelling/contraction dynamics of a strongly charged gel immersed in a copper
      sulphate solution were studied. Changes in the size of the gel particle and the
      penetration of metal ions inside the network were monitored by optical
      microscopy. The equilibrium state was attained in two steps: First, the gel
      swells, mainly by absorbing water, and then it collapses, to the almost dry
      state. The release of copper ions from the contracted gel when it was placed in
      acidic medium was studied as a function of time using optical microscopy. The
      influence of the acid concentration on the rate of ion release and on changes in
      the particle size of the gel are discussed.

PMID- 9766251
TI  - Self-assembled hydrogel nanoparticle of cholesterol-bearing pullulan as a carrier
      of protein drugs: complexation and stabilization of insulin.
AB  - Insulin (Ins) spontaneously and easily complexed with the hydrogel nanoparticle
      of hydrophobized cholesterol-bearing pullulan (CHP) in water. The complexed
      nanoparticles (diameter 20-30 nm) thus obtained formed a very stable colloid. The
      thermal denaturation and subsequent aggregation of Ins were effectively
      suppressed upon complexation. The complexed Ins was significantly protected from
      enzymatic degradation. Spontaneous dissociation of Ins from the complex was
      barely observed, except in the presence of bovine serum albumin. The original
      physiological activity of complexed Ins was preserved in vivo after i.v.
      injection.

PMID- 9766252
TI  - Coupling of the antiviral agent zidovudine to polyaspartamide and in vitro drug
      release studies.
AB  - A macromolecular prodrug of the known antiretroviral agent zidovudine and alpha,
      beta-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) was synthesized. A succinic
      spacer was present between the polymer and the drug, and 1,1'-carbonyldiimidazole
      was used as the coupling agent. In vitro drug release studies at pH 1.1, 5.5 and
      7.4 indicated that limited amounts of intact drug were released from the
      conjugate. At pH 1.1 and 7.4 succinylzidovudine was released, and this was
      hydrolysed to give free zidovudine. In the presence of alpha-chymotrypsin,
      zidovudine was released preferentially in comparison with the succinyl
      derivative. The amounts of released zidovudine and succinylzidovudine were
      greater in plasma than in aqueous buffer solutions. These results show that after
      i.v. administration this drug-polymer conjugate can release zidovudine into the
      blood circulation for prolonged periods.

PMID- 9766253
TI  - Enhanced neuroendocrine response to insulin tolerance test performed under
      increased ambient temperature.
AB  - The hypothesis that an increase in ambient temperature modulates neuroendocrine
      response in clinically used provocative pituitary function tests was verified.
      Healthy male volunteers were subjected to insulin tolerance tests in two
      randomized trials. In the first trial hypoglycemia was induced by a bolus
      injection of insulin (0.1 U per kg of BW, i.v.) at room temperature. In the
      second trial, the subjects were exposed to increased ambient temperature for 45
      min before insulin injection and for 45 min thereafter. The environmental
      temperature was selected to increase body temperature less than 1C. Under
      conditions of increased temperature basal hormone levels as measured in
      antecubital venous blood samples failed to be modified and the hypoglycemia was
      less severe. Nevertheless, the responses of most (beta-endorphin, ACTH,
      prolactin, catecholamines), but not all (growth hormone, cortisol), hormones to
      hypoglycemia were exaggerated. The remarkable increase in ACTH and beta-endorphin
      release was not accompanied by concomitant increase of plasma cortisol response.
      The sympathetic-adrenomedullary system was significantly activated, which was
      manifested particularly by enhanced norepinephrine release. Growth hormone
      response to hypoglycemia was not modified, while that of prolactin was enhanced.
      Thus during evaluation of neuroendocrine function under clinical conditions,
      changes in ambient and body temperature should not be underestimated.

PMID- 9766254
TI  - Growth hormone secretion in Prader-Willi syndrome.
AB  - Prader-Willi Syndrome (PWS) is a multisystem defect characterized by obesity,
      hypogenitalism and short stature for genetic background. Low GH serum levels have
      been found in patients with PWS and were related to a hypothalamic-pituitary
      dysfunction. We studied spontaneous nocturnal GH secretion and GH-response to
      provocative tests in five patients affected by PWS. We observed in three of them
      (Group A) abnormally low GH and IGF-1 serum levels. In the other two patients
      (Group B) GH secretion and IGF-1 serum levels were normal. In all patients no
      thyroid dysfunction was observed. These data might suggest the presence of two
      different subgroups of patients affected by PWS, from an endocrinological point
      of view. An abnormally low GH secretion would be evident only in a subgroup of
      patients, which appears to be normal in the remaining patients. This casistic is
      small in number, but if our data will be confirmed by more extensive studies it
      may be possible to identify a specific population of PWS patients who could
      benefit from recombinant GH-therapy.

PMID- 9766255
TI  - Effect of low-dosage recombinant human growth hormone therapy on pulmonary
      function in hypopituitary patients with adult-onset growth hormone deficiency.
AB  - An impairment of the pulmonary function has been described in adult patients with
      childhood-onset growth hormone deficiency (GHD). We examined forced vital
      capacity (FVC), forced expiratory volume (FEV1), total lung capacity (TLC),
      functional residual capacity (FRC), residual volume (VR) and the index of
      inspiratory strength, middle tidal volume and tidal inspiratory time ratio
      (TV/I), in 29 patients with adult-onset GHD. Data were compared with those
      obtained in 46 healthy control subjects. Only the FEV1/FVC ratio was
      statistically different (p = 0.04) between the two groups of subjects. In a group
      of 15 GHD patients low dosages (0.5-1 IU/day s.c., bedtime) of recombinant human
      GH (rh-GH; n. = 8 subjects) or placebo (n. = 7) were given at random for a 6
      month period. A significant increase in IGF-I levels was noted in the rh-GH
      treated group (p = 0.04) but not in the placebo group. After the 6-month period
      no statistically significant changes in pulmonary function were found between the
      rh-GH-treated and placebo-treated GHD patients. This study shows that adult-onset
      GHD patients suffer from minimal impairment of pulmonary function. Low rh-GH
      dosages able to induce an increase in IGF-I levels do not improve pulmonary
      function. The effect of rh-GH on respiratory muscle strength could be related to
      the age at which GHD diagnosis is made, or induced only by high rh-GH dosages
      given for a long time.

PMID- 9766256
TI  - Endocrinological aspects of Langerhans cell histiocytosis complicated with
      diabetes insipidus.
AB  - Langerhans cell histiocytosis (LCH) is a rare disorder and may be complicated
      with hypopituitarism and diabetes insipidus (DI) due to invasion of the
      hypothalamic-pituitary area. In this study, 10 patients with complete (4) and
      partial (6) type central DI were found among 125 LCH patients in our hospital
      records. The water deprivation test, followed by the pitressin test, was
      performed to confirm DI. Hypothalamic-pituitary endocrine function tests were
      carried out on these 10 patients at the initial diagnosis and during follow-up.
      All patients revealed growth hormone insufficiency in the insulin hypoglycemic
      tolerance test. Four patients had impairment of cortisol secretion, demonstrated
      by insulin hypoglycemic stimulating test results. Two patients had poor response
      in the thyrotropin releasing hormone stimulating test. Two patients had only
      partial responses in the luteinizing hormone releasing hormone test. Four
      patients had hyperprolactinemia. All patients underwent surgical treatment
      followed by chemotherapy and/or radiotherapy. One patient completely recovered
      from the endocrine disorder, 3 patients required smaller doses of desmopressin,
      and one patient had normal adrenal, thyroid, and gonadal function. Hypothalamic
      pituitary disorders in LCH should not be neglected. Treatment of LCH can
      partially or completely reverse associated endocrine disorders. Therefore,
      endocrine studies and hormone replacement should be mandatory for patients with
      LCH.

PMID- 9766258
TI  - Growth hormone binding protein activity in obese children.
AB  - We evaluated growth hormone binding protein (GHBP) activity in a group of obese
      children (12 boys and 12 girls, age 3.1-14.7 years, BMI 21.1-33.3, 11 prepubertal
      and 13 early pubertal) and in 26 age-matched normal weight children (14 boys and
      12 girls, age 2.1-16.0 years, BMI 14.2-21.4, 18 prepubertal and 8 early
      pubertal). All children were of normal stature. GHBP activity was significantly
      higher in the obese (39.1 +/- 1.1%) than in the control children (28.3 +/- 1.0%,
      p < 0.0001). Mean serum GHBP was not different between boys and girls or between
      prepubertal and pubertal subjects. A positive correlation was found between BMI
      and GHBP levels only in the normal weight children (r = 0.425, p < 0.05).
      Baseline insulin concentrations in the obese children were 97.6 +/- 7.9 pmol/l
      (normal values, 45.0 +/- 18.6 pmol/l), and the mean insulin AUC following OGTT in
      the obese was 811.3 +/- 160.7 pmol/l (normal values, 373.1 +/- 150.1 pmol/l).
      Serum GHBP activity in the obese was not correlated with baseline serum insulin
      concentrations or with the insulin AUC following OGTT. In conclusion, we found
      that obese children have elevated GHBP activity, and speculate that this
      phenomenon may serve to compensate for their reduced GH secretion and accelerated
      GH clearance.

PMID- 9766257
TI  - Immunohistochemical detection of glycoprotein hormone alpha subunit in
      somatoprolactinic and pure somatotroph adenomas.
AB  - Glycoprotein hormone alpha subunit (alpha SU) is expressed in nearly all
      thyreotroph adenomas and most gonadotrophinomas, but is less well documented in
      plurisecreting adenomas. We therefore examined the immunohistochemical (IHC)
      expression of alpha SU in a generally accepted model of plurisecreting adenomas
      (somatoprolactinic type) by comparison to a series of pure monosecreting
      somatotroph tumors. Fifty patients (32 females, 18 males) aged 15 to 68 years
      with clinical and/or biological acromegaly requiring adenomectomy were studied.
      Forty-five had clinical acromegaly and 5 had isolated amenorrhea and/or
      galactorrhea syndromes. Forty-eight of the 49 patients who had baseline
      assessments of plasma GH had a mean concentration of 5 ng/ml or more (normal
      value < 5). Fifteen of the 46 patients who had baseline measurements of plasma
      PRL had a prolactinemia value greater than 20 ng/ml (normal value < 20) but below
      100 ng/ml, except for one patient. All the adenomas studied were positive by GH
      immunohistochemistry; 21 were immunostained by an antiPRL antibody and formed the
      "somatoprolactinic" (GH-PRL) group. Five of these 21 patients were male. The 12
      female patients younger than 50 years had amenorrhea or galactorrhea, and one
      male patient complained of impotence. Eleven patients (9 females, 2 males) in
      this GH-PRL group had hyperprolactinemia. Sixteen of these GH-PRL adenomas were
      immunolabeled by alpha SU antiserum. The remaining 29 adenomas, which were
      immunonegative with the PRL antibody and formed the "somatotroph adenoma" (GH)
      group, were more frequent in male patients (13/29; 45%) compared to GH-PRL group.
      Eight amenorrhea or galactorrhea syndromes occurred among the 14 women younger
      than 50 years, 3 of whom had hyperprolactinemia. Thirteen of these 29 adenomas
      (45%) were immunopositive with alpha SU antibody. Compared to the GH group, the
      GH-PRL group had a significant higher frequency of amenorrhea and/or galactorrhea
      syndromes among women under 50 years (100% vs 57%; p < 0.01), as well as
      hyperprolactinemia (55% vs 15%; p < 0.01) and positive alpha SU immunoreactivity
      (76% vs 45%; p < 0.05). The frequency of extrasellar macroadenomas was not
      different according to PRL or alpha SU immunoreactivity. Thus, in this series of
      somatoprolactinic adenomas, alpha SU immunopositivity was slightly more frequent
      than in a control group of pure somatotroph adenomas. Moreover,
      hyperprolactinemia was more frequent in patients with GH-PRL adenomas, although
      the size of the pure and mixed adenomas was not different. These results suggest
      that hyperprolactinemia and/or alpha SU immunopositivity are more often
      associated with mixed GH-PRL adenomas.

PMID- 9766259
TI  - Papillary microcarcinoma of the thyroid.
AB  - Papillary microcarcinoma of the thyroid has been often detected by aspiration
      biopsy cytology performed with ultrasonographic guidance. Autopsy studies also
      have often revealed small thyroid carcinomas, and it was concluded that most
      small thyroid carcinomas should not be regarded as a clinical matter. In this
      study, 112 patients with papillary microcarcinoma 10 mm or less in size treated
      between 1992 and 1995 were analyzed. There were 104 females and 8 males, with a
      mean age of 46.0 years. Diagnosis of papillary carcinoma was made preoperatively
      in 100 of these patients (89.3%), and 77 patients underwent aspiration biopsy
      cytology under ultrasound guidance. Seventy of these patients underwent modified
      neck dissection, and 63.8% of these patients had lymph node metastases. The
      number of lymph node metastasis increased as primary tumor size increased. There
      was no clear border or clinical differences between primary tumors 10 mm or less
      and tumors more than 10 mm. One patient had lymph node recurrence after surgery
      and another patient had recurrent nerve palsy at the first visit. Based on these
      findings, papillary microcarcinoma should be treated surgically.

PMID- 9766261
TI  - Different effects of octreotide by continuous night infusion at increasing rate
      or by evening injections at different times on morning hyperglycemia and growth
      hormone levels in insulin-dependent diabetic patients.
AB  - The effect of octreotide on morning hyperglycemia and GH levels was evaluated in
      eight insulin-dependent diabetic patients. Octreotide (50 mcg) was administered
      through subcutaneous injections at different hours (20:00, 22:00 and 24:00 h) or
      through continuous subcutaneous night infusion from midnight to 08:00 at
      increasing rate between 03:00 and 08:00 h. After octreotide injection at midnight
      we noticed a sharp decrease of both glycemia (p < 0.005) and GH (p < 0.05) at
      04:00 h, but not at 08:00 h. Only the night continuous infusion at increasing
      rate was able to reduce glycemia and GH at 04:00 and at 08:00 h (p < 0.001 and p
      < 0.01 respectively). The injections of octreotide at 20:00 and 22:00 h lowered
      GH values at 24:00 h (p < 0.01 and p < 0.05 vs insulin alone) but did not show
      any significant effect on blood glucose levels and GH at 04:00 and 08:00 h. In
      conclusion, only the continuous subcutaneous night infusion of octreotide at
      increasing rate during the last hours of the night was able to reduce
      simultaneously morning hyperglycemia and GH levels in insulin-dependent diabetic
      patients, whereas evening subcutaneous injections at different times did not show
      any appreciable effect.

PMID- 9766262
TI  - The use of colour slides in the assessment of changes in soft-tissue involvement
      in Graves' ophthalmopathy.
AB  - There is a need for more reliable and validated methods to assess the eye changes
      in Graves' disease. Such measurements are now available for the assessment of
      proptosis, eye muscle dysfunction, and optic nerve involvement. However, no
      validated objective measurement exists for NO SPECS class II signs. The present
      study compares the use of colour slides with clinical grading for assessing soft
      tissue involvement. Forty-three patients were treated with retrobulbar
      irradiation. Pre-treatment, and 6 months post-treatment the severity of class II
      signs was graded from 0 to grade c in two ways; 1) Clinically, by two
      independent, experienced observers, who recorded their scores on the same day; 2)
      From colour slides, taken at the same visits, which were graded afterwards in one
      session independently by the same observers. Inter-observer agreement about
      clinical grading was low (Kappa 0.32), and was not improved by using the slides
      (Kappa 0.35). However, by using the clinical scores, the observers disagreed on
      treatment outcome in 21/43 patients (49%), whereas using the slides disagreement
      occurred in only 6/43 (14%, p < 0.01). It is concluded that the grading of soft
      tissue involvement is highly subjective. However, the use of colour slides does
      provide a more reliable way to assess a treatment effect and should be used in
      clinical trials.

PMID- 9766260
TI  - Effect of acute corticotropin releasing factor on pituitary-adrenocortical
      responsiveness in elderly women and men.
AB  - Aging is related to critical changes of the hypothalamo-pituitary-adrenal
      function. A decline in serum DHEA levels has been demonstrated in healthy elderly
      subjects, while ACTH and cortisol concentrations remain at normal values. The
      purpose of the present study was to investigate the effect of aging on pituitary
      adrenal responsiveness to hCRF in subjects of both sexes. A group of 12
      physically and mentally healthy elderly subjects and a group of 12 young controls
      of both sexes have been selected. Blood samples were collected before and after
      i.v. bolus injection of hCRF; ACTH, cortisol and DHEA levels were then determined
      by RIA. Basal ACTH and cortisol levels did not result statistically different
      between controls and elderly subjects, while DHEA showed a clear and significant
      age-related decrease (p < 0.01). Following the hCRF injection, the responses of
      ACTH, cortisol and DHEA in aged subjects were higher than in young controls; ACTH
      (p < 0.03) and cortisol (p < 0.01) were higher in aged women than in men. The
      present study demonstrated that aging is associated with an increased
      responsiveness of ACTH, cortisol and DHEA to exogenous hCRF supply. A
      hyperactivation of the pituitary-adrenal secretory activity may explain the age
      related of the same axis. Gender probably has a significant influence on basal
      and stimulated hormonal secretion. In conclusion, hCRF test may become a useful
      clinical tool in establishing a neuroendocrine correlation with central
      disturbances associated to aging.

PMID- 9766263
TI  - Hypoglycemia unawareness in a patient with dumping syndrome: report of a case.
AB  - We report the case of a 49-yr-old man affected by coma and hypoglycemia
      unawareness following repetitive hypoglycemic episodes due to dumping syndrome.
      The dumping syndrome, which was due to partial gastrectomy and vagotomy performed
      for recurrent peptic ulcer, was responsible for reactive hyperinsulinemia as
      demonstrated by an oral glucose tolerance test. While the glucose
      counterregulatory hormones were all normally sensitive to specific stimulation
      tests, insulin-induced hypoglycemia failed to induce an adequate
      counterregulatory response, causing no response in plasma norepinephrine, a
      slight and short increase in plasma cortisol, ACTH and glucagon and an
      insufficient increase in plasma epinephrine and GH. This case demonstrates that
      hypoglycemia unawareness has to be taken into account not only in patients
      affected by IDDM or insulinoma but also in any case of reactive hypoglycemia.

PMID- 9766264
TI  - Ablative or non-ablative therapy for Graves' hyperthyroidism in patients with
      ophthalmopathy?

PMID- 9766265
TI  - Ablative or non-ablative therapy for Graves' hyperthyroidism in patients with
      ophthalmopathy?
AB  - In our view there are no properly controlled trials which support a beneficial
      effect on ophthalmopathy from surgical or radioiodine-based deliberate ablation
      for hyperthyroidism. The theoretical basis for this approach can be questioned
      and we still know too little about the pathogenesis of ophthalmopathy to draw any
      firm conclusions about the likely effects of ablation. There are established
      risks with ablation. Like the majority of European thyroidologists, we prefer
      antithyroid drugs for the initial treatment of hyperthyroidism complicated by
      Graves' ophthalmopathy and individualise treatment for recurrent hyperthyroidism
      based on the patient's preference, but do not recommend ablation routinely in
      presence of eye signs.

PMID- 9766267
TI  - Neuroendoscopy. Personal experience, indications and limits.
AB  - The authors report a series of 40 patients treated by endoscopic neurosurgery. It
      includes 31 cases of obstructive hydrocephalus, 4 paraventricular or
      intraventricular CSF cysts, 3 cases of multiloculated hydrocephalus, one
      suprasellar arachnoid cyst and one cystic astrocytoma with mural tumor nodule.
      Third ventriculostomy is the most frequent indication of the endoscopic
      neurosurgery, which is very useful also for performing fenestration of CSF cysts
      and multiloculated hydrocephalus. The surgical endoscopic techniques in the
      different above mentioned pathologies are exposed. The criteria for patient
      selection, the clinical results and the postoperative radiological findings, that
      confirm the patency of the fenestration, are discussed.

PMID- 9766268
TI  - Nerve regeneration over a 20-mm gap through a nerve conduit containing blood
      vessels in rats: the influence of interstump distance on nerve regeneration.
AB  - BACKGROUND: The present study was conducted in rats to investigate whether a tube
      with additional intrachamber vascularization could permit axons to extend over a
      distance greater than 10 mm, which appears to be the maximum axon regeneration
      distance for rat sciatic nerve axons through a normal empty tube. METHODS: A
      sural vessel-containing tube (VCT) was designed and interposed between transected
      sciatic nerve stumps in the thigh, leaving a 20-mm interneural gap. RESULTS:
      Twelve weeks after tubulation, six out of nine rats showed successful nerve
      regeneration and re-innervation of the soleus muscle using the VCT. At 24 weeks,
      intrachamber nerve regeneration and re-innervation of the soleus and pedal
      adductor muscles were electrophysiologically and histologically confirmed in all
      rats. However, no neural tissue was observed within any ligated sural vessel
      containing tube (LVCT) or empty unmodified tube (ET) with a 20-mm interneural
      gap. When nerves regenerated in the VCT with a 20-mm gap were compared with those
      regenerated in a VCT with a 10-mm gap 12 and 24 weeks after surgery, the results
      produced by the VCT with a 20-mm gap were inferior to those after use of the VCT
      with a 10-mm gap, except for motor nerve conduction velocity at 24 weeks.
      CONCLUSIONS: The value recovered to almost identical levels (about 50-60% normal)
      in both groups.

PMID- 9766269
TI  - High-dose heparin plus warfarin administration in non-traumatic dural sinuses
      thrombosis. A clinical and neuroradiological study.
AB  - BACKGROUND: The management of intracranial dural sinuses thrombosis is still
      controversial and uncertain. The authors report the cases of 7 patients with non
      traumatic thrombosis of the dural sinuses and describe the most important
      radiographic findings, the indication, effectiveness of antithrombotic therapy,
      and outcome. METHODS: A retrospective review was conducted of 7 cases of dural
      sinus thrombosis admitted, between 1994 and 1996, to our division. All patients
      underwent full anticoagulation therapy. Heparin was administered, using a dose of
      25,000 units/day for two weeks; warfarin was given using a dose of 5 mg twice
      daily. Treatment course was followed by maintenance treatment with a single
      administration of 5 mg/day of warfarin. All patients were submitted to close
      titration and coagulation profile monitoring. RESULTS: In 4 cases Magnetic
      Resonance Imaging-Angiography (Angio-MRI) was performed for following up the
      recanalization of the sinuses, resulting a persistent no patency of the dural
      sinuses. Three patients underwent contrast-enhanced CT scan, demonstrated an
      "empty delta sign" in the sagittal sinus, confirming no recanalization.
      Nevertheless, six patients had have a good quality recovery, and one patient a
      moderate disability. DISCUSSION: Cerebral venous sinus thrombosis is an uncommon
      cause of cerebral infarction, and may be mistaken, unless specifically sought.
      The natural history of the disease is highly variable, with a mortality rates
      range from 10% to 20%. At present, in our opinion, the venous phase of Angio-MRI
      is the definitive examination, and a gold standard for diagnosis of dural sinus
      thrombosis. In our cases, antithrombotic therapy has been found to be a safe and
      effective treatment, despite contrast-CT scans and Angio-MRI showed no
      recanalization of the sinuses, in all patients.

PMID- 9766266
TI  - Role of GnRH drive in the pathophysiology of polycystic ovary syndrome.
AB  - Polycystic ovary syndrome may result from multiple mechanisms, but full
      expression of the PCO syndrome with hyperandrogenic anovulation depends upon
      sustained LH drive and relative FSH deficiency. We have described possible
      intrinsic and extrinsic factors capable of modifying the hypothalamic-pituitary
      ovarian axis. Available evidence suggests the presence of an intrinsic alteration
      in GnRH-LH drive. The long-term natural history of HAA is variable and depends on
      several factors including obesity, aberrations in insulin action, intrinsic
      ovarian function, and end-organ responsiveness to androgens. Figure 1 presents a
      conceptualization of the pathogenesis of PCOS diagramming the multiple modulators
      of its expression. Long-term suppression of androgens when fertility is not
      desired should modify the full expression of the PCO syndrome. It is important to
      appreciate that therapy with oral contraceptive agents has few drawbacks and many
      immediate and potential long-term benefits for women with HAA. This therapy may
      be of greatest benefit when started in adolescence prior to the progression of
      obesity, hirsutism, and thecal-stromal hyperplasia. Women with HAA represent a
      large subgroup of patients who require individualization of their health care
      with sensitivity to issues surrounding anovulation, obesity, hirsutism, and
      infertility.

PMID- 9766270
TI  - CBF change with aging in moyamoya disease.
AB  - The change of cerebral blood flow (CBF) with aging was analyzed in 9 cases of
      moyamoya disease whose age ranged from 16 years old to 58 years old. CBF
      decreased more prominently in the various lobes with aging than control subjects
      and the decrement was more rapid in the affected side than in the non-affected
      side. CBF was thought to decrease with the hemorrhagic attack and the
      accompanying neurological deterioration. However the gradually-deteriorating
      brain damages caused by the chronic hypoperfusion also might be engaged in this
      CBF decrement.

PMID- 9766271
TI  - Choroid plexus papillomas of the posterior fossa: extraventricular extension,
      intraventricular and primary extraventricular location. Report of four cases.
AB  - Four cases of Choroid Plexus Papilloma (CPP) of the posterior fossa are
      presented. Two cases had extraventricular extension from the fourth ventricle to
      the Cerebellopontine Angle (CPA) through the foramen of Luschka, in one the CPP
      was located primarily in the CPA and the fourth case was only in the fourth
      ventricle. CPP are rare tumours of the Central Nervous System and primary
      extraventricular location is extremely rare. We know that primary location in the
      extraventricular and intraventricular regions and extraventricular extension have
      different pathological mechanisms. The main purpose of this paper is to discuss
      and review some possible explanations for these mechanisms.

PMID- 9766273
TI  - Peduncular hallucinosis following a transoral odontoidectomy for cranio-vertebral
      junction malformation. A case report.
AB  - This is a case report of a sixty-two years old man suffering from a cranio
      vertebral malformation whose dens epistrophei was removed through a transoral
      approach. During the postoperative course, he experienced a transient peduncular
      hallucinosis probably caused by surgical trauma on his brainstem. The possible
      physiopathological, etiopathological, clinical, and therapeutic aspects of this
      rare phenomenon are discussed.

PMID- 9766272
TI  - Association between an aneurysm of the anterior inferior cerebral artery and an
      arteriovenous malformation fed by the same artery.
AB  - An unusual case of distal aneurysm of the anterior inferior cerebellar artery
      (AICA) associated with a cerebellar arteriovenous malformation in a 35 year-old
      woman is reported. The clinical presentation was a subarachnoid hemorrhage, that
      is the sudden onset of headache while she was driving her car. In the following
      days the patient experienced a cerebellopontine angle syndrome: unsteadiness,
      tinnitus and hearing loss in her left ear, along with drop episodes. All symptoms
      disappeared in about a week. She consulted a neurosurgeon only a month later. On
      the day of admission in the Neurosurgical Department of Residence du Parc Clinic
      her neurological status was normal. Neuroradiological investigations showed the
      association between the two distal AICA malformations. At surgery it was possible
      either to clip the aneurysm or to remove the AVM. The origin of the hemorrhage
      has not been clearly identified. The patient had an uneventful recovery and
      returned to her job three months later. The aneurysm was located on the same
      artery that supplied the AVM. This association is rare at the AICA level. The
      possible development of the aneurysm induced by increase in flow through the AVM
      is discussed in the light of Literature data.

PMID- 9766274
TI  - A possible sequela of transoral approach to the upper cervical spine.
      Velopharyngeal incompetence.
AB  - The authors describe a case of velopharyngeal incompetence (VPI), as a
      consequence to the neurosurgical treatment for a complex malformation of the
      cranio-spinal junction. A 61-year-old woman underwent a transoral-transvelar
      surgical approach for odontoid resection. One month later surgical fixation of
      the posterior spine with autologous iliac bone graft was performed. Following
      these operations the patient presented a marked alteration of speech
      intellegibility due to hypernasal voice resonance and through incapability to
      articulate the oral phonemes correctly. She also complained of nasal
      regurgitation of fluids and solids while swallowing. She underwent a clinical
      phoniatric assessment of voice and speech. Videonasopharyngoscopy allowed us to
      inspect the velopharyngeal sphincter and to show clearly the type and morphology
      of its closure defect. Correction of VPI was achieved by means of a
      velopharyngoplasty (pharyngeal flap), in spite of technical difficulties due to
      local scarring and to a problematic exposure of the surgical field.

PMID- 9766275
TI  - Intracerebral schwannoma. Case report.
AB  - A case of intraparenchymal schwannoma is presented. A 61-year-old woman, with
      stigmata of von Recklinghausen's neurofibromatosis (NF-2), presented with a
      history of weakness of the right lower limb for 2 months. She was investigated by
      MR which showed a circular mass with a maximum diameter of 5 cm in the right
      parieto-occipital lobe. The tumor was removed in toto via a left parieto
      occipital craniotomy. The patient was discharged two weeks after the operation
      and remains well now 2 years later. The clinical and neuroradiological findings
      of reported intraparenchymal schwannomas, including the case reported here, are
      discussed.

PMID- 9766276
TI  - A fatal acute subdural hematoma occurring after evacuation of "contralateral"
      chronic subdural hematoma.
AB  - Although chronic subdural hematomas (SDHs) are bilateral in about 20% of the
      cases, an acute SDH in one side associated with chronic SDH in "contralateral"
      side is an extremely rare and devastating condition. In this report, a case of
      "contralateral" acute SDH occurring after evacuation of chronic SDH in one side
      is presented. The clinical history, complaints, neurological and
      neuroradiological findings, and pathophysiological mechanisms of this uncommon
      entity are discussed and related literature is reviewed.

PMID- 9766277
TI  - Revisiting the high-tech/high-touch dilemma.

PMID- 9766278
TI  - The use of haloperidol to treat nausea.

PMID- 9766279
TI  - Keeping surgical drains open.

PMID- 9766280
TI  - Lymphedema and exercise.

PMID- 9766282
TI  - Recognizing and treating dysfunctional grief.

PMID- 9766281
TI  - Fentanyl for dyspnea relief.

PMID- 9766283
TI  - Care of the patient with perineal skin injury.

PMID- 9766284
TI  - Apheresis unit preparation for patients receiving peripheral blood stem cells.

PMID- 9766285
TI  - Additional tips from members. Promoting environmentally responsible health care.

PMID- 9766286
TI  - DNA testing for cancer predisposition.
AB  - PURPOSE/OBJECTIVES: To describe and review scientific and regulatory aspects of
      molecular genetic technology in the context of DNA testing for cancer
      predisposition. DATA SOURCES: Published professional articles, texts, and
      proceedings; commercial testing companies; computerized data bases; and the World
      Wide Web. DATA SYNTHESIS: This article reviews the basic molecular biology (e.g.,
      DNA, genes, chromosomes, DNA mutations) that is the foundation for indirect and
      direct methods of DNA testing for cancer predisposition. Key issues in DNA
      testing include who should be tested, provision of testing, and regulatory
      concerns. Benefits and problems of testing contribute to its current
      controversial status. CONCLUSIONS: Understanding the mechanisms of DNA testing
      for cancer requires knowledge of basic molecular biology. Family history of the
      cancer in question is a key indicator for predisposition testing. Accessing
      information regarding research-based testing is challenging. DNA testing for
      cancer predisposition is not a perfect test, as exemplified by issues related to
      test regulation and sensitivity. IMPLICATIONS FOR NURSING PRACTICE: Basic
      knowledge of DNA testing for cancer predisposition will help nurses to (a) have a
      better understanding of the indications for and ramifications of testing, (b)
      provide information about testing to patients and the lay public, (c) counsel
      patients and families at high risk for inherited cancers more effectively, and
      (d) interpret DNA test results.

PMID- 9766287
TI  - End-of-life confusion in patients with cancer.
AB  - PURPOSE/OBJECTIVES: To review the literature on confusion at the end of life,
      provide accurate definitional and defining characteristics of confusion, and
      outline nursing strategies for its resolution. DATA SOURCES: Published articles,
      computerized databases, book chapters, reference lists from chapters and journal
      articles. DATA SYNTHESIS: As a major component of symptom distress in terminal
      care, confusion has not been defined clearly and therefore has not benefited from
      rigorous assessment and study as have other end-of-life symptoms. CONCLUSIONS:
      Increased knowledge about confusion that occurs in patients with widely
      metastatic cancer will assist in accurate symptom identification, early
      recognition, and timely management to reduce cognitive symptom distress at the
      end of life. Improved symptom resolution also can benefit family coping during
      terminal care. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses can devise
      management protocols for confused patients that include screening criteria,
      pharmacologic interventions, environmental support, and prophylactic safety
      measures.

PMID- 9766289
TI  - Leptomeningeal metastasis: pathophysiology, treatment, and nursing management.
AB  - PURPOSE/OBJECTIVES: To review the pathophysiology, diagnosis, and clinical
      treatment of leptomeningeal metastasis. DATA SOURCES: Published articles,
      abstracts, and book chapters. DATA SYNTHESIS: Leptomeningeal metastasis is an
      increasingly seen complication of cancer. Treatment is intensive and may increase
      survival from four to five weeks without treatment to an average of six months.
      Clinical management and treatment of these patients is complex and best
      accomplished by a multi-disciplinary healthcare team. CONCLUSIONS: Information
      regarding the anatomy, pathophysiology, treatment, and treatment complications
      can facilitate the care of patients with leptomeningeal metastasis. IMPLICATIONS
      FOR NURSING PRACTICE: Nursing interventions should focus on patient and family
      education about the disease process, side-effects of treatment, and early
      identification of disease progression.

PMID- 9766288
TI  - Measuring the information needs of husbands of women with breast cancer: validity
      and reliability of the Family Inventory of Needs--husbands.
AB  - PURPOSE/OBJECTIVES: A two-phase study was undertaken to test the Family Inventory
      of Needs--Husbands (FIN-H), a tool designed to measure the information needs of
      husbands of women with breast cancer and the extent to which these needs are met.
      DESIGN: Methodologic survey. SAMPLES: Phase I: a panel of 6 husbands; phase II:
      84 husbands of women with breast cancer. METHODS: Panel of expert ratings
      followed by pilot test of the two-part survey. FINDINGS: In phase I, husbands
      assessed the FIN-H for clarity, internal consistency, and content validity. All
      preset criteria were met. In phase II, internal consistency, test-retest
      reliability, and internal validity were assessed. Internal consistency estimates
      as measured by Cronbach's standardized alpha coefficients were 0.91 and 0.93.
      Test-retest correlations were 0.82 and 0.76 (p = 0.0001). Exploratory factor
      analysis suggested that the FIN-H consists of five factors. CONCLUSIONS: Initial
      results suggest that the FIN-H is reliable and valid. Further testing is needed
      to confirm these results. IMPLICATIONS FOR NURSING PRACTICE: Before nurses can
      address the information needs of husbands of women with breast cancer, use of a
      reliable and valid assessment tool is recommended.

PMID- 9766291
TI  - Family-level services in oncology nursing: facts, fallacies, and realities
      revisited.

PMID- 9766290
TI  - Effects of dialogue and therapeutic touch on preoperative and postoperative
      experiences of breast cancer surgery: an exploratory study.
AB  - PURPOSE/OBJECTIVES: To obtain preliminary data and determine the feasibility of a
      large-scale experimental study to test the efficacy of the Rogerian Science of
      Unitary Human Beings-based intervention of dialogue and therapeutic touch (TT) on
      pre- and postoperative anxiety and mood and postoperative pain from breast cancer
      surgery. DESIGN: Experimental. SETTING: Mid-Atlantic region; ambulatory. SAMPLE:
      29 Caucasian and 2 African American English-speaking women with positive breast
      cancer biopsy (experimental, n = 14; control, n = 17), ranging in age from 31-84
      years old (F = 55.6). METHODS: Treatments administered in subjects' homes within
      seven days prior to surgery and 24 hours after hospital discharge. Experimental
      treatment consisted of 10 minutes of TT and 20 minutes of dialogue. Control
      treatment consisted of 10 minutes of quiet time and 20 minutes of dialogue. Data
      (Spielberger State-Trait Anxiety Inventory. Affects Balance Scale, and Visual
      Analog Scale-Pain) were collected at the conclusion of each home visit. MAIN
      RESEARCH VARIABLES: Anxiety, mood, and pain. FINDINGS: The experimental group had
      lower preoperative state anxiety than the control groups (p = 0.008). No
      difference was found for preoperative mood. No differences were found for any
      postoperative measure. CONCLUSIONS: A large-scale study of dialogue and TT would
      require changes in design and recruitment strategies. IMPLICATIONS FOR NURSING
      PRACTICE: Nurses may provide more comprehensive care by incorporating dialogue
      and TT or quiet time into their pre- and postoperative care. Additional research,
      however, is recommended to determine the differential effects of dialogue, TT,
      and quiet time on women's experiences with breast cancer prior to incorporating
      these noninvasive modalities into clinical practice.

PMID- 9766292
TI  - Establishing mechanisms to conduct multi-institutional research--fatigue in
      patients with cancer: an exercise intervention.
AB  - PURPOSES/OBJECTIVES: To describe the process of establishing a multi
      institutional interdisciplinary team of oncology researchers and conducting a
      pilot study of an exercise intervention for fatigue. DATA SOURCES: Project
      meeting minutes and records, research team members' logs, subjects' research
      records, the research study proposal, and team members' individual and collective
      shared experiences. DATA SYNTHESIS: Site investigators established research teams
      at five academic medical centers. Fifty subjects were enrolled in the study and
      tested during their cancer treatment. Study methods, including instrumentation,
      were evaluated carefully and revised. CONCLUSIONS: The multi-institutional
      network of researchers is an effective and efficient model for testing an
      intervention to manage fatigue during cancer treatment. IMPLICATIONS FOR NURSING
      PRACTICE: Exercise is a feasible and potentially beneficial intervention to
      combat distressing cancer treatment-related fatigue. A pilot study is essential
      to determine the best methods for conducting a clinical trial and to develop the
      teams of researchers necessary for such a project.

PMID- 9766293
TI  - Planning and conducting a multi-institutional project on fatigue.
AB  - PURPOSE/OBJECTIVES: To describe the process used in proposal development and
      study implementation for a complex multisite project on cancer treatment-related
      fatigue (CRF), identify strategies used to manage the project, and provide
      recommendations for teams planning multisite research. DATA SOURCES: Information
      derived from project team meeting records, correspondence, proposals, and
      personal recollection. DATA SYNTHESIS: The project was built on preexisting
      relationships among the three site investigators who then built a team including
      faculty, research coordinators, staff nurses, and students. Study sites had a
      range of organizational models, and the proposal was designed to capitalize on
      the organizational and resource strengths of each setting. Three team members
      drawn from outside oncology nursing provided expertise in measurement and
      experience with fatigue in other populations. Planning meetings were critical to
      the success of the project. Conference calls, fax technology, and electronic mail
      were used for communication. Flexibility was important in managing crises and
      shifting responsibility for specific components of the work. The team documented
      and evaluated the process used for multisite research, completed a major
      instrumentation study, and developed a cognitive-behavioral intervention for CRF.
      CONCLUSIONS: Accomplishments during the one-year planning grant exceeded initial
      expectations. The process of conducting multisite research is complex, especially
      when the starting point is a planning grant with specific research protocols to
      be developed and implemented over one year. Explicit planning for decision-making
      processes to be used throughout the project, acknowledging the differences among
      the study settings and planning the protocols to capitalize upon those
      differences, and recruiting a strong research team that included a member with
      planning grant and team-building expertise were essential elements for success.
      IMPLICATIONS FOR NURSING PRACTICE: Specific recommendations for others planning
      multisite research are related to team-building, team membership, communication,
      behavioral norms, role flexibility, resources, feedback, problem management, and
      shared recognition.

PMID- 9766294
TI  - Developing a team for multicultural, multi-institutional research on fatigue and
      quality of life.
AB  - PURPOSE/OBJECTIVES: To describe the process of establishing a multisite team to
      conduct research with a multicultural focus on fatigue. DATA SOURCES: Articles,
      book chapters, personal experience. DATA SYNTHESIS: Teamwork facilitated
      development of a productive professional working group, sharing of resources, and
      data collection culminating in a research proposal for studying cancer-related
      fatigue in a multicultural population. CONCLUSIONS: Establishing a common goal by
      investing time, committing to the process, and establishing trust was the secret
      to effective team functioning. IMPLICATIONS FOR NURSING PRACTICE: The prospect of
      multi-institutional collaboration has implications for oncology nurses in the
      areas of research and practice. Goals that could not be achieved easily in the
      setting of a single institution are reached more easily with multisite
      collaboration and teamwork.

PMID- 9766295
TI  - Distress, symptom distress, and immune function in women with suspected breast
      cancer.
AB  - PURPOSE/OBJECTIVES: To investigate distress and its association with immune
      function among women with suspected breast cancer. DESIGN: Prospective,
      descriptive, correlational study. SETTING: An outpatient breast clinic at a
      tertiary urban hospital. SAMPLE: A convenience sample of women who had either a
      fine needle aspiration or open breast biopsy for a suspicion of breast cancer.
      Thirty-five women comprised the study sample, 6 with malignant and 29 with benign
      tumors. METHODS: Data were collected at three points in time. The first time (T1)
      was after the physician visit when the need for breast biopsy was ascertained.
      The second time (T2) was 7-10 days postbiopsy, and the third time (T3) was 7-10
      days after T2. At T1, T2, and T3, participants filled out the Brief Symptom
      Inventory (a measure of psychological distress) and the Adapted Symptom Distress
      Scale (a measure of symptom distress) and provided a blood sample. Demographic
      data also were collected at T1. Immune function was measured by serum cytokine
      levels of transforming growth factor beta (TGF beta) and tumor necrosis factor
      alpha (TNF alpha). MAIN RESEARCH VARIABLES: Psychological distress, symptom
      distress, and immune function. FINDINGS: Psychological distress scores were
      moderate to high. Symptom distress was either nonexistent or slight. Significant
      correlations between psychological distress and symptom distress were found at T2
      and T3. At T2, significant relationships between psychological distress and TNF
      alpha and between symptom occurrence and TNF alpha were found. Psychological and
      symptom distress scores were significantly different between women with malignant
      versus benign tumors at all three times. No differences in cytokine levels were
      found between the groups. CONCLUSIONS: These results suggest the strong effect
      that the diagnostic process has on psychological distress and its potential
      effects on immune functioning. Distress was significantly greater for women with
      malignant disease; however, women with benign disease continued to have elevated
      levels of distress. IMPLICATIONS FOR NURSING PRACTICE: Nurses should be aware of
      the extremely stressful nature of the diagnostic phase and should continue to
      provide support, knowing that this distress continues throughout this phase,
      particularly for women diagnosed with malignancy.

PMID- 9766296
TI  - Clinical care for patients receiving autologous hematopoietic stem cell
      transplantation in the home setting.
AB  - PURPOSE/OBJECTIVES: To undertake a pilot study of autologous hematopoietic stem
      cell transplantation (HSCT) in the patient's home to improve satisfaction of
      care, reduce financial costs, and relieve pressure on inpatient accommodation.
      DESIGN: Descriptive, cross-sectional, qualitative. SETTING: Patients' homes
      within the metropolitan area of Perth, Australia. SAMPLE: 25 Caucasian adults
      with recurrent multiple myeloma, non-Hodgkin's lymphoma, or Hodgkin's disease
      requiring autologous HSCT. METHODS: A program was developed to use the bone
      marrow transplant team from a major tertiary hospital to permit home visiting,
      treatment with cytotoxic chemotherapy at home, treatment of complications at
      home, and an integrated home/hospital caring facility to expedite hospital
      admission if complications developed. FINDINGS: The program was practical to
      administer, improved overall patient satisfaction, and was significantly less
      costly than inpatient transplantation. Fifteen patients (60%) of the total study
      group of 25 required hospital admission for a median of five days (range 1-13
      days) for management of complications, predominantly febrile neutropenia.
      Nineteen (76%) of the 25 patients received i.v. antibiotic therapy at home during
      the period of neutropenia. Two patients died of transplant-related complications-
      one from respiratory syncytial virus infection and one from veno-occlusive
      disease of the liver. These complications were not attributable to the home
      setting. IMPLICATIONS FOR NURSING PRACTICE: This program increased the
      responsibility and sense of autonomy of advanced practice nurses and developed
      their counseling skills as well as their ability to participate more actively in
      the decision-making process of those involved. MAIN RESEARCH VARIABLES:
      Participation in the home transplant program, patient satisfaction, nursing
      development, and cost-effectiveness of the program.

PMID- 9766297
TI  - Assessing master's programs in advanced practice oncology nursing.

PMID- 9766298
TI  - Craniocerebral trauma: protection and retrieval of the neuronal population after
      injury.
AB  - OBJECTIVE: To review the consequences of mechanical injury to the brain with an
      emphasis on factors that may explain the variability of outcomes and how this
      might be influenced. METHODS: Information regarding the pathophysiology of
      traumatic brain damage contained in original scientific reports and in review
      articles published in recent years was reviewed from the perspective of a
      clinical neurosurgeon and a neuropathologist, each with major research interests
      in traumatic brain damage. The information was compiled on the basis of the
      knowledge of and personal selection of articles that were identified through
      selective literature searches and current awareness profiles. A systematic
      literature review was not conducted. RESULTS: Mechanical input affects neuronal
      and vascular elements and is translated into biological effects on the brain
      through a complex series of interacting cellular and molecular events. Whether
      these lead to permanent structural damage or to resolution and recovery is
      determined by the balance between processes that, on the one hand, mediate the
      effects of initial injury and subsequent secondary insults and, on the other, are
      manifestations of the brain's protective, reparative response. Experimental and
      clinical research has identified opportunities for altering the balance in a way
      that might promote recovery, but data demonstrating that this can lead to
      substantial clinical benefit are lacking. Recent evidence of genetically
      determined, individual susceptibility to the effects of injury may explain some
      of the puzzling variability in outcome after apparently similar insults and may
      also provide new opportunities for treatment. CONCLUSION: The understanding of
      traumatic brain damage that is being gained from recent research is widening and
      broadening perspectives from the traditional focus on mechanical, vascular, and
      metabolic effects to encompass wider, neurobiological issues, drawn from the
      fields of neurodevelopment, neuroplasticity, neurodegeneration, and
      neurogenetics. Neurotrauma is a fascinating area of neuroscience research, with
      promise for the translation of knowledge to improved clinical management and
      outcome.

PMID- 9766300
TI  - Intraoperative brain shift and deformation: a quantitative analysis of cortical
      displacement in 28 cases.
AB  - OBJECTIVE: A quantitative analysis of intraoperative cortical shift and
      deformation was performed to gain a better understanding of the nature and extent
      of this problem and the resultant loss of spatial accuracy in surgical procedures
      coregistered to preoperative imaging studies. METHODS: Three-dimensional feature
      tracking and two-dimensional image analysis of the cortical surface were used to
      quantify the observed motion. Data acquisition was facilitated by a ceiling
      mounted robotic platform, which provided a number of precision tracking
      capabilities. The patient's head position and the size and orientation of the
      craniotomy were recorded at the start of surgery. Error analysis demonstrated
      that the surface displacement measuring methodology was accurate to 1 to 2 mm.
      Statistical tests were performed to examine correlations between the amount of
      displacement and the type of surgery, the nature of the cranial opening, the
      region of the brain involved, the duration of surgery, and the degree of
      invasiveness. RESULTS: The results showed that a displacement of an average of 1
      cm occurred, with the dominant directional component being associated with
      gravity. The mean displacement was determined to be independent of the size and
      orientation of the cranial opening. CONCLUSION: These data suggest that loss of
      spatial registration with preoperative images is gravity-dominated and of
      sufficient extent that attention to errors resulting from misregistration during
      the course of surgery is warranted.

PMID- 9766299
TI  - Intraoperative magnetic resonance imaging with the magnetom open scanner:
      concepts, neurosurgical indications, and procedures: a preliminary report.
AB  - OBJECTIVE: Intraoperative magnetic resonance imaging (MRI) is now available with
      the General Electric MRI system for dedicated intraoperative use. Alternatively,
      non-dedicated MRI systems require fewer specific adaptations of instrumentation
      and surgical techniques. In this report, clinical experiences with such a system
      are presented. METHODS: All patients were surgically treated in a "twin operating
      theater," consisting of a conventional operating theater with complete
      neuronavigation equipment (StealthStation and MKM), which allowed surgery with
      magnetically incompatible instruments, conventional instrumentation and operating
      microscope, and a radiofrequency-shielded operating room designed for use with an
      intraoperative MRI scanner (Magnetom Open; Siemens AG, Erlangen, Germany). The
      Magnetom Open is a 0.2-T MRI scanner with a resistive magnet and specific
      adaptations that are necessary to integrate the scanner into the surgical
      environment. The operating theaters lie close together, and patients can be
      intraoperatively transported from one room to the other. This retrospective
      analysis includes 55 patients with cerebral lesions, all of whom were surgically
      treated between March 1996 and September 1997. RESULTS: Thirty-one patients with
      supratentorial tumors were surgically treated (with navigational guidance) in the
      conventional operating room, with intraoperative MRI for resection control. For 5
      of these 31 patients, intraoperative resection control revealed significant tumor
      remnants, which led to further tumor resection guided by the information provided
      by intraoperative MRI. Intraoperative MRI resection control was performed in 18
      transsphenoidal operations. In cases with suspected tumor remnants, the surgeon
      reexplored the sellar region; additional tumor tissue was removed in three of
      five cases. Follow-up scans were obtained for all patients 1 week and 2 to 3
      months after surgery. For 14 of the 18 patients, the images obtained
      intraoperatively were comparable to those obtained after 2 to 3 months.
      Intraoperative MRI was also used for six patients undergoing temporal lobe
      resections for treatment of pharmacoresistant seizures. For these patients, the
      extent of neocortical and mesial resection was tailored to fit the preoperative
      findings of morphological and electrophysiological alterations, as well as
      intraoperative electrocorticographic findings. CONCLUSION: Intraoperative MRI
      with the Magnetom Open provides considerable additional information to optimize
      resection during surgical treatment of supratentorial tumors, pituitary adenomas,
      and epilepsy. The twin operating theater is a true alternative to a dedicated MRI
      system. Additional efforts are necessary to improve patient transportation time
      and instrument guidance within the scanner.

PMID- 9766301
TI  - Long-term graft patency rates and clinical outcomes after revascularization for
      symptomatic traumatic internal carotid artery dissection.
AB  - INTRODUCTION: Surgical management of traumatic internal carotid artery (ICA)
      dissection remains controversial. Therefore, the delayed outcomes and graft
      patency rates of patients who underwent bypass procedures for symptomatic
      traumatic ICA dissection were studied. METHODS: Between September 1989 and August
      1996, 13 patients (9 male and 4 female patients; mean age, 30.6 yr) underwent 16
      revascularization procedures for symptomatic traumatic ICA dissection. The
      duration of clinical follow-up averaged 47.3 months (range, 12-94 mo) from the
      date of diagnosis. The duration of radiographic follow-up (catheter or magnetic
      resonance angiography, duplex Doppler ultrasonography) averaged 24 months (range,
      12-60 mo). RESULTS: ICA dissection was caused by blunt (n = 11) or penetrating
      trauma (n = 2). Associated angiographic abnormalities included seven ipsilateral
      ICA occlusions, six dissecting aneurysms, two carotid-cavernous fistulae, and six
      contralateral traumatic ICA dissections. Patients requiring early
      revascularization (n = 6) underwent bypass procedures an average of 19.2 days
      after their injuries. Medically managed patients who developed ischemia later
      were revascularized a mean of 7.8 months after injury. The mean Glasgow Coma
      Scale score at the time of presentation was 10 (range, scores of 6-15), and the
      mean Glasgow Coma Scale score before revascularization was 14 (range, scores of 9
      15). There were 14 saphenous vein ICA bypasses (8 cervical-to-petrous, 3 cervical
      to-middle cerebral artery, 3 petrous-to-supraclinoid) and 2 superficial temporal
      artery-to-middle cerebral artery bypasses. There was one early postoperative
      graft occlusion, which responded to surgical thrombectomy. One patient with
      multiple other traumatic injuries died as a result of a pulmonary embolus 12
      months after revascularization. All remaining patients had Glasgow Outcome Scale
      scores of 5, with patent bypass grafts confirmed during follow-up. CONCLUSION:
      Revascularization for persistently symptomatic traumatic ICA dissection
      eliminated ischemia and was associated with excellent long-term outcomes and
      graft patency rates.

PMID- 9766302
TI  - The differences in electroencephalographic changes in patients undergoing carotid
      endarterectomies while under local versus general anesthesia.
AB  - OBJECTIVE: This study compared the electroencephalographic (EEG) changes
      occurring during carotid occlusion in 225 consecutive patients undergoing carotid
      endarterectomies performed by two surgeons, one using local and the other using
      general anesthesia. METHODS: A retrospective review of patients undergoing
      carotid endarterectomies for carotid occlusive disease was conducted. EEG changes
      associated with intraoperative ischemia (decreased amplitude, generalized
      slowing, and loss of fast activity) resulting in the need for an indwelling
      arterial shunt were recorded for the two anesthesia groups. To determine the
      similarities or differences between the two groups, the groups were compared
      regarding age, risk factors, and indications for surgery. RESULTS: Significant
      EEG changes were noted in 6 of 96 patients (6.3%) in the local anesthesia group
      versus 19 of 121 patients (15.7%) in the general anesthesia group. EEG changes
      consisted solely of generalized slowing in the local anesthesia group, whereas a
      more varied spectrum was observed in the general anesthesia group. The two groups
      were similar regarding age and risk factors. Although the local anesthesia group
      had more asymptomatic patients, symptomatic patients did not have a greater
      incidence of EEG changes. CONCLUSION: There is a large difference in EEG changes
      potentially requiring shunt placement in patients undergoing surgery while under
      local (6.3%) versus general (15.7%) anesthesia. This could not be explained based
      on age, risk factors, interpretation of EEG findings, or indications between the
      two groups. We conclude that EEG monitoring may be insensitive and may fail to
      detect ischemia in patients who are under regional anesthesia. Alternately, the
      presence of general anesthetics may alter the character of the EEG findings and
      increase the sensitivity of EEG monitoring to ischemic events.

PMID- 9766303
TI  - Asymptomatic familial cerebral aneurysms.
AB  - PURPOSE: We evaluated the prevalence and features of cerebral aneurysms in the
      family members of people with asymptomatic aneurysms among 8680 participants
      undergoing magnetic resonance angiography. METHODS: Of the 8680 participants, 380
      had family histories of aneurysms and 8300 did not. The prevalence and features
      of asymptomatic aneurysms were compared in these two subgroups. In addition, the
      prevalence in all living first- or second-degree relatives was evaluated in 20
      families. RESULTS: The prevalence of asymptomatic aneurysms was 7.0% (606 of 8680
      participants) overall and 10.5% (40 of 380 participants) and 6.8% (566 of 8300
      participants) in the subgroups with and without family histories of aneurysms,
      respectively. The prevalence in the female participants with family histories of
      aneurysms (12.3%, 28 of 228 participants) was higher than that in the male
      participants with family histories of aneurysms (7.9%, 12 of 152 participants) (P
      < 0.0001). Compared with the entire group, this subgroup more commonly showed
      aneurysms situated at the junction of the internal carotid and posterior
      communicating arteries (P < 0.0005) and at the middle cerebral artery (P <
      0.0001). The prevalence of aneurysms in 115 members of the 20 families was 33.9%.
      Although the members of 14 families with aneurysmal subarachnoid hemorrhage
      showed higher prevalence of ruptured and asymptomatic aneurysms (42.1%) than did
      the members of 6 families with only asymptomatic aneurysms (17.9%), the former
      had very low prevalence of asymptomatic aneurysms. CONCLUSION: The prevalence of
      aneurysms is significantly elevated in family members of people with asymptomatic
      aneurysms. It is suggested that familial asymptomatic aneurysms are more likely
      to rupture in families having members with aneurysmal subarachnoid hemorrhage
      than in those without.

PMID- 9766304
TI  - Too little, too late: does tirilazad mesylate reduce fatigue after subarachnoid
      hemorrhage?
AB  - OBJECTIVE: Trials assessing drug effectiveness for treatment of subarachnoid
      hemorrhage (SAH) often use mortality rates and Glasgow Outcome Scale scores as
      outcome measures. Neuropsychological and psychosocial measures might be more
      sensitive to outcomes, especially for patients of better-grade status. METHODS:
      Eighteen of a total of 31 patients enrolled in the New Zealand arm of the Upjohn
      international, double-blind, therapeutic trial of tirilazad mesylate for women
      with SAH were assessed neuropsychologically and psychosocially 3 months after
      SAH. The 13 not assessed either had died or remained vegetative (9 patients), did
      not speak English (1 patient), or did not consent (3 patients). The drug code was
      broken after all assessments had been scored. RESULTS: Sixteen of the 31 patients
      had received the drug and 15 the vehicle. There were no differences between the
      two groups with respect to age, grades assessed at admission and 14 weeks after
      SAH, Glasgow Outcome Scale scores assessed at 3 months, or mortality rates. In
      the subgroup assessed neuropsychologically, nine patients were in each of the
      drug- and vehicle-treated groups. No differences were found with respect to
      grades, Glasgow Outcome Scale scores, or values for an index that measured
      cognitive impairment in all tests, but vehicle-treated patients were more
      impaired with respect to measures of concentration, sustained attention, and
      psychomotor speed (P < 0.02), as well as debilitating fatigue (P < 0.01).
      CONCLUSION: The finding that the patients in the drug-treated group exhibited
      fewer impairments typical of diffuse cortical damage could be viewed as being
      consistent with the hypothesis that tirilazad mesylate protects neurons. Given
      the small size of this study, these results require confirmation with larger
      patient groups. Future drug trials should consider including neuropsychological
      tests in assessments of outcomes after SAH. If this is too costly, questions
      regarding fatigue levels might prove worthwhile.

PMID- 9766305
TI  - Nonneoplastic intramedullary spinal cord lesions mimicking tumors.
AB  - OBJECTIVE: We report a group of nine patients with atypical, nonneoplastic
      intramedullary spinal cord lesions. By retrospectively reviewing these patients,
      we hoped to elucidate characteristics that would identify these patients as
      harboring nonneoplastic lesions before surgical intervention. METHODS: We
      reviewed the histological findings of 212 patients undergoing surgery for
      intramedullary spinal cord tumors between 1989 and 1994. We identified nine
      patients with nonneoplastic lesions (4%); case histories and radiographs were
      reviewed. RESULTS: All patients were evaluated preoperatively using magnetic
      resonance imaging. The extent of enhancement with gadolinium varied from
      homogeneous enhancement to no enhancement. All lesions showed marked T2 changes.
      There was a lack of significant spinal cord expansion associated with the lesions
      in all cases. All patients underwent surgery. The histology of the surgical
      specimens showed demyelinating lesions in four patients, sarcoidosis in two
      patients, amyloid angiopathy in two patients, and a mass of nonneoplastic
      inflammatory cells of unknown origin in one patient. CONCLUSION: Although it was
      difficult to antecedently distinguish these lesions from neoplastic spinal cord
      tumors by case history and physical examination, the most consistent clue was
      absent or minimal spinal cord expansion on the preoperative magnetic resonance
      images.

PMID- 9766306
TI  - Lateral extracavitary approach for thoracic and thoracolumbar spine trauma:
      operative complications.
AB  - BACKGROUND: The lateral extracavitary approach (LECA) to the thoracic and
      thoracolumbar spine allows ventral decompression and dorsal fixation of the spine
      through the same incision during a single procedure. The approach, however, is
      technically demanding and time-consuming. We sought to determine the incidence of
      complications associated with the LECA in patients with acute thoracolumbar spine
      injuries. PATIENTS AND METHODS: A retrospective chart review of all patients with
      acute fractures or dislocations of the thoracic or thoracolumbar spine who
      underwent surgery via the LECA was conducted to assess the incidence and type of
      perioperative complications associated with the LECA. RESULTS: Thirty-three
      patients with thoracic or thoracolumbar spine injuries treated using the LECA
      between June 1990 and June 1996 were identified and had available medical
      records. Complications occurred in 18 of these patients. Pulmonary complications
      predominated. Eleven patients required tube thoracostomy for hemothorax or
      persistent pleural effusions, and seven patients developed postoperative
      pneumonia. There were no cases of neurological worsening. There was no mortality.
      CONCLUSION: Decompression and stabilization of acute thoracolumbar fractures with
      the LECA in the acute setting is associated with a 55% incidence of morbidity.
      Whereas some of this morbidity may be attributed to the effects of the injury,
      there is a certain intrinsic morbidity associated with the LECA. Although this
      morbidity may compare favorably with that of sequential ventral/dorsal
      approaches, the biomechanical advantages obtained with a combined ventral and
      dorsal construct must be balanced against the inherent morbidity of such
      approaches.

PMID- 9766307
TI  - Microvascular decompression for pediatric onset trigeminal neuralgia.
AB  - BACKGROUND: Trigeminal neuralgia (TGN) is generally a disease of the elderly.
      Vascular compression, the causative agent in the majority of cases, is thought to
      result from atherosclerotic changes within the vessels of the posterior fossa.
      Rarely, the disease presents during childhood, before the onset of severe
      atherosclerotic changes. We therefore sought to explore the role of vascular
      compression in pediatric patients with medically refractory TGN. PATIENTS AND
      METHODS: Twenty-three patients were identified in whom the onset of typical TGN
      had occurred during childhood (age 18 yr or younger) and who underwent
      exploration of the cerebellopontine angle. Twenty-two of 23 underwent
      microvascular decompression (MVD) of the trigeminal nerve. Twenty-one of these
      patients were followed for more than 1 year. A retrospective chart review was
      conducted to determine the efficacy of MVD for the treatment of TGN in this
      select population. Operative findings were recorded and correlated with patient
      outcome. RESULTS: Twenty-two of 23 patients (96%) were found to have vascular
      compression of the trigeminal nerve at the time of exploration. One patient was
      found to have an epidermoid tumor. MVD resulted in complete pain relief at the
      time of discharge in 16 of 22 patients (73%), with an additional 4 patients (18%)
      having a greater than 75% diminution of pain. The 21 patients who were followed
      for at least 1 year were followed for a mean of 105 months. At the time of their
      last follow-up, 9 of these patients (43%) continued to have complete pain relief
      and 3 (14%) had a greater than 75% diminution of pain. The most common operative
      finding was a vein compressing the nerve, often in combination with a branch of
      the superior cerebellar artery. DISCUSSION: MVD has been demonstrated to be a
      safe and efficacious treatment for TGN in the adult population. Patients whose
      symptoms begin in childhood do not enjoy the same therapeutic response to MVD as
      do patients with TGN onset in adulthood. An increased incidence of venous
      compression was noted in this population, as was a longer duration of symptoms
      before MVD. These factors may be responsible for the decreased efficacy of MVD in
      this patient population.

PMID- 9766308
TI  - Pediatric low-grade gliomas: prognosis with proton magnetic resonance
      spectroscopic imaging.
AB  - OBJECTIVE: Our aim was to assess the correlation between the low-grade glioma
      (LGG) metabolic profile and tumor progression. Using in vivo proton magnetic
      resonance spectroscopic imaging, we specifically asked whether and which
      metabolic features are associated with tumor regrowth or recurrence. METHODS:
      Eleven pediatric patients with histologically proven partially resected (<20%
      resection) midline LGG were treated and followed up for a period of 2 years. All
      patients underwent proton magnetic resonance spectroscopic imaging studies before
      any management was determined. Tumor progression was defined as radiological
      evidence of mass enlargement (>25%) during the follow-up period. Proton magnetic
      resonance spectroscopic imaging was performed using a PRESS-CSI sequence on a
      General Electric 1.5-tesla scanner (General Electric Medical System, Waukesha,
      WI). The signal intensities of N-acetylaspartate, choline (CHO), and creatine
      from the tumor and the normal brain were used to calculate normalized metabolite
      intensities and metabolite ratios. RESULTS: Tumors that progressed during a 2
      year period displayed higher normalized CHO than those that remained stable (Mann
      Whitney test, P < 0.03). The majority (five of six) of the rapidly growing LGG
      showed values of normalized CHO of at least 1, whereas the nonprogressors had a
      normalized CHO value of less than 1. CONCLUSION: In association with pediatric
      LGG, high normalized CHO values seem to herald the potential for rapid tumor
      growth. These observations may be valuable for defining subsets of patients with
      LGG who may benefit from early therapeutic interventions.

PMID- 9766309
TI  - Depth electrode implantation in the length axis of the hippocampus for the
      presurgical evaluation of medial temporal lobe epilepsy: a computed tomography
      based stereotactic insertion technique and its accuracy.
AB  - OBJECTIVE: An individualized computed tomography-based stereotactic technique for
      the longitudinal insertion of intrahippocampal electrodes is presented and its
      accuracy described. METHODS: The technique makes use of one well reproducible
      target in the hippocampal head and of the approximate inclination of the
      anteroposterior length axis of the hippocampus, for which the orbital floor is
      taken as an auxiliary landmark. It was used in 141 patients with medically
      intractable complex partial seizures. In 106 patients, magnetic resonance imaging
      (MRI) was available for assessment of implantation accuracy. Each of the 212
      electrodes was plotted on topographic drawings and its goodness of fit rated.
      RESULTS: Whereas hippocampal head and body were hit by 97 and 96% of the
      electrodes, respectively, the amygdala was hit by only 75% of the electrodes and
      mainly at its basal margin. For 93% of the electrodes, the inclination in a
      sagittal plane corresponded exactly to that of the hippocampus. The implantation
      morbidity amounted to 5.7%, whereas permanent neurological deficit occurred in
      one (0.7%) of the 141 patients. CONCLUSION: This computed tomography-based
      protocol proved to be reliable and hence can be considered as an adequate
      alternative to MRI-based stereotactic implantation if MRI is not available or if
      a single MRI-based stereotactic set-up is unreliable because of intolerable
      distortions.

PMID- 9766310
TI  - Low-frequency ultrasound penetrates the cranium and enhances thrombolysis in
      vitro.
AB  - OBJECTIVE: Refinements of treatment methods are sought to rapidly reduce the
      volume of intracranial clots and to decrease patient exposure to possible
      complications of thrombolytic therapy for intracranial hematomas. We assessed the
      possibility of adding ultrasonication using model systems including human blood
      clots and temporal bone in vitro. METHODS: The transmittance of ultrasound
      through temporal bone obtained at autopsy was compared between the frequencies
      211.5 KHz and 1.03 MHz, using a meter to determine the power delivered. The
      frequency 211.5 KHz was chosen to assess the ultrasound effect on the weight of
      24-hour-old clots prepared from human blood after exposures at 37 degrees C to 2
      mg/ml urokinase with no additional treatment, ultrasound, or agitation during an
      interval of up to 12 hours. At these times, fibrin degradation products also were
      measured. RESULTS: The transmittance of low-frequency ultrasound (211.5 KHz)
      through temporal bone was approximately 40%, which is four times higher than that
      of high-frequency ultrasound (1.03 MHz). Ultrasound but not agitation
      significantly increased clot lysis (140% of lysis with urokinase alone), with
      correspondingly increased fibrin degradation products. CONCLUSION: We conclude
      that low-frequency ultrasound transmits well through human temporal bone and
      enhances thrombolysis in vitro. Clinically, this method may be promising for
      reducing dosages of thrombolytic agents and shortening the period of clot
      removal.

PMID- 9766312
TI  - Surgical anatomy of the infratemporal fossa: the styloid diaphragm revisited.
AB  - INTRODUCTION: The infratemporal fossa (ITF) gives passage to most major cerebral
      vessels and cranial nerves. Dissection of the ITF is essential in many of the
      lateral cranial base approaches and in exposure of the high cervical internal
      carotid artery (ICA). We reviewed the surgical anatomy of this region. METHODS:
      Direct foraminal measurements were made in seven dry skulls (14 sides), and the
      relationship of these foramina to each other and various landmarks were
      determined. Ten ITF dissections were performed using a preauricular subtemporal
      infratemporal approach. Preliminary dissections of the extracranial great vessels
      and structures larger than 1 cm were performed using standard macroscopic
      surgical techniques. Dissection of all structures less than 1 cm was conducted
      using microsurgical techniques and instruments, including the operating
      microscope. The anatomic relationships of the muscles, nerves, arteries, and
      veins were carefully recorded, with special emphasis regarding the relationship
      of these structures to the styloid diaphragm. The dissection was purely
      extradural. RESULTS: The styloid diaphragm was identified in all specimens. It
      divides the ITF into the prestyloid region and the retrostyloid region. The
      prestyloid region contains the parotid gland and associated structures, including
      the facial nerve and external carotid artery. The retrostyloid region contains
      major vascular structures (ICA, internal jugular vein) and the initial exocranial
      portion of the lower Cranial Nerves IX through XII. Landmarks were identified for
      the different cranial nerves. The bifurcation of the main trunk of the facial
      nerve was an average of 21 mm medial to the cartilaginous pointer and an average
      of 31 mm medial to the tragus of the ear. The glossopharyngeal nerve was found
      posterior and lateral to stylopharyngeus muscle in nine cases and medial in only
      one. The vagus nerve was consistently found in the angle formed posteriorly by
      the ICA and the internal jugular vein. The spinal accessory nerve crossed
      anterior to the internal jugular vein in five cases and posterior in another five
      cases. It could be located as it entered the medial surface of the
      sternocleidomastoid muscle 28 mm (mean) below the mastoid tip. The hypoglossal
      nerve was most consistently identified as it crossed under the
      sternocleidomastoid branch of the occipital artery 25 mm posterior to the angle
      of the mandible and 52 mm anterior and inferior to the mastoid tip. CONCLUSION:
      The styloid diaphragm divides the ITF into prestyloid and retrostyloid regions
      and covers the high cervical ICA. Using landmarks for the exocranial portion of
      the lower cranial nerves is useful it identifying them and avoiding injury during
      approaches to the high cervical ICA, the upper cervical spine, and the ITF.

PMID- 9766311
TI  - Optical coherence tomography for neurosurgical imaging of human intracortical
      melanoma.
AB  - OBJECTIVE: Intraoperative identification of brain tumors and tumor margins has
      been limited by either the resolution of the in vivo imaging technique or the
      time required to obtain histological specimens. Our objective was to evaluate the
      feasibility of using optical coherence tomography (OCT) as a high-resolution,
      real-time intraoperative imaging technique to identify an intracortical melanoma.
      INSTRUMENTATION: OCT is a new, noncontact, high-speed imaging technology capable
      of resolutions on the micrometer scale. OCT is analogous to ultrasound B-mode
      imaging, except that reflections of infrared light, rather than sound, are
      detected. OCT uses inherent tissue contrast, rather than enhancement with dyes,
      to differentiate tissue types. The compact, fiberoptic-based design is readily
      integrated with surgical instruments. METHODS: A portable handheld OCT surgical
      imaging probe has been constructed for imaging within the surgical field.
      Cadaveric human cortex with metastatic melanoma was harvested and imaged in two
      and three dimensions. Changes in optical backscatter intensity were used to
      identify regions of tumor and to locate tumor margins. Structures within the
      optical coherence tomographic images were compared with the histological slides.
      RESULTS: Two-dimensional images showed increased optical backscatter from regions
      of tumor, which was quantitatively used to determine the tumor margin. The images
      correlated well with the histological findings. Three-dimensional reconstructions
      revealed regions of tumor penetrating normal cortex and could be resectioned at
      arbitrary planes. Subsurface cerebral vascular structures could be identified and
      were therefore avoided. CONCLUSION: OCT can effectively differentiate normal
      cortex from intracortical melanoma based on variations in optical backscatter.
      The high-resolution, high-speed imaging capabilities of OCT may permit the
      intraoperative identification of tumor and the more precise localization of tumor
      margins.

PMID- 9766313
TI  - A paramedian tangential approach to lumbosacral extraforaminal disc herniations.
AB  - OBJECTIVE: Extraforaminal disc herniations today are operated on via the so
      called lateral approach. Clinical experience has shown that in contrast to levels
      L2/3-L4/5, this approach may become extremely difficult at the L5-S1 level.
      According to new microanatomic studies, the previous lateral approaches at this
      level often do not allow access to the neuroforamen without partial or total
      destruction of the L5-S1 facet joint. Postoperatively, this may lead to joint
      irritation with consecutive low back and pseudoradicular pain. To preserve the
      facet joint, a new approach was developed based on an anatomic study. METHODS:
      The approach was first considered with the help of bone specimens including
      ilium, vertebra 5, and sacrum. Thereafter, lumbar maceration specimens were
      prepared leaving ligaments, intervertebral discs, and joints intact. From these
      specimens, bony and ligamentous landmarks were deduced. Finally, the approach was
      tested on seven cadavers. Subsequently, the approach was performed on 13 patients
      and the intraoperative findings, the clinical feasibility, and the postoperative
      results were analyzed. APPROACH: After a transverse skin incision above the
      dorsal curvature of the ilium, the paravertebral muscles are dissected from the
      ilium medially toward the spinous process. Lateral from the apophyseal joint, a
      canal is drilled through the spongiosa of the sacrum. Primarily, a thin layer of
      inner cortex is spared to protect the content of the neuroforamen. Subsequently,
      it can easily be removed with the dissector to enter the extraforaminal space. In
      the depth of the drilled canal, the nerve root is found, because it is fixed at
      the sacrum near the disc space by the anterior lumbosacral ligaments. Riding on
      the nerve root, the intertransverse ligament and muscle can be removed with the
      punch. It is then possible to see the neuroforamen and extraforaminal space in
      front of the joint. Free fragments and contained discs can then easily be found
      and removed. CONCLUSION: Using this new approach, the L5-S1 joint remains intact.
      Space for instrumental manipulations is created in areas not essential for joint
      function. For this procedure, newly defined anatomic landmarks, such as the
      ileolumbar ligament, upper edge of the sacrum, lateral rim of the apophyseal
      joint, and para-articular notch, guide the operative route. In accordance with
      the preliminary anatomic studies, this approach was successfully used in 13
      patients, and we think that it is a promising alternative that helps to preserve
      joint function and dorsal root ganglion integrity.

PMID- 9766314
TI  - Endothelin and subarachnoid hemorrhage: an overview.
AB  - INTRODUCTION: Delayed cerebral vasospasm occurring after subarachnoid hemorrhage
      (SAH) is still responsible for a considerable percentage of the morbidity and
      mortality in patients with aneurysms. It has been suggested that the pathogenesis
      of delayed cerebral vasospasm is related to a number of pathological processes,
      including endothelial damage and smooth muscle cell contraction resulting from
      spasmogenic substances generated during lysis of subarachnoid blood clots,
      changes in vascular responsiveness, and inflammatory or immunological reactions
      of the vascular wall. It has been recognized that the endothelium plays an
      important role in the regulation of the cerebral vascular tone. In 1988,
      endothelin (ET)-1, a potent vasoconstrictor, was isolated from cultured porcine
      aortic endothelial cells. RESULTS: ET-1, which is one of three distinct isoforms
      of ETs (ET-1, ET-2, and ET-3), has a more marked effect on cerebral arteries than
      do the other two isoforms. Elevated levels of ETs have been demonstrated in the
      cerebrospinal fluid and plasma of patients after SAH and cerebral infarction. ETs
      act by at least three different receptor subtypes, the ET(A) receptor, which is
      localized in vascular smooth muscle cells and mediates vasoconstriction, and two
      different ET(B) receptor subtypes. The ET(B1) receptor subtype is present in
      vascular endothelial cells and mediates the endothelium-dependent vasodilation.
      The ET(B2) receptor subtype is present in smooth muscle cells causing
      vasoconstriction. ET-1 acts from the adventitial but not from the luminal side of
      cerebral arteries. In vivo and in vitro ET-1 causes a dose-dependent and long
      lasting vasoconstriction, similar to cerebral vasospasm after SAH. The
      vasoconstriction caused by ET-1 can be reversed by selective ET(A) receptor
      antagonists or combined ET(A) and ET(B) receptor antagonists. CONCLUSION: The
      results of current clinical and experimental investigations support the
      hypothesis that ET-1 is a major cause of cerebral vasospasm after SAH. Other
      studies indicate that SAH causes complex changes in the ET system and increased
      ET-1 levels after SAH, which are not solely responsible for the development of
      vasospasm but may occur after cerebral ischemia. Further investigations are
      therefore needed to clarify these different hypotheses.

PMID- 9766315
TI  - Strategies to circumvent vascular barriers of the central nervous system.

PMID- 9766316
TI  - Improving drug delivery to intracerebral tumor and surrounding brain in a rodent
      model: a comparison of osmotic versus bradykinin modification of the blood-brain
      and/or blood-tumor barriers.
AB  - OBJECTIVE: To compare transient blood-brain barrier disruption (BBBD) by
      hypertonic mannitol with pharmacological modification of the blood-tumor barrier
      by the vasoactive peptide bradykinin for delivery of small and large agents to
      nude rat intracerebral xenografts. METHODS: Female nude rats (n = 104) with 6-day
      intracerebral human small cell lung carcinoma tumors were treated using BBBD (n =
      24), intracarotid bradykinin (n = 38), or saline (controls, n = 32) administered
      intra-arterially. During or immediately after infusion, the rats were given
      radiolabeled agent (methotrexate or dextran 70; Dupont NEN, Boston, MA). The rats
      were killed 10 minutes later, and samples of tumor and brain regions were
      obtained for scintillation counting. Twenty-two additional rats were examined
      using magnetic resonance imaging after administering one of two contrast agents
      (gadoteridol or iron oxide nanoparticles) or saline (controls) in conjunction
      with BBBD or bradykinin. RESULTS: After BBBD, the delivery of both small
      (methotrexate) and large (dextran 70) radiolabeled tracers was increased 2- to 6
      fold in the tumor and 3- to 20-fold in surrounding brain, as compared with saline
      controls. After bradykinin treatment, there was minimal change in delivery of
      methotrexate or dextran 70 to tumor and brain around tumor, with the greatest
      increase less than 60% over controls. Magnetic resonance imaging demonstrated
      increased delivery of both small and large contrast agents to the treated
      hemisphere after BBBD. In comparison, no increased tumor enhancement could be
      detected after bradykinin treatment. CONCLUSION: BBBD resulted in global delivery
      of a variety of agents in a wide range of sizes. In this human brain tumor
      xenograft model, bradykinin was not effective at increasing delivery to the tumor
      of any agent tested.

PMID- 9766317
TI  - Expression of endothelin(A) receptors in human gliomas and meningiomas, with high
      affinity for the selective antagonist PD156707.
AB  - OBJECTIVE: Endothelin (ET) immunoreactivity, ET production, and specific ET
      receptors have been identified in the brain. Changes in ET concentration or
      receptor expression have been implicated in the pathophysiological changes in
      vasospasm after subarachnoid hemorrhage and in cerebral neoplasia. In this study,
      we have characterized the ET(A) and ET(B) receptor subtypes present in human
      normal cerebral cortex (NCC) and two common central nervous system tumors, i.e.,
      meningioma (MNG) and glioblastoma multiforme (GBM). A knowledge of the ET
      receptor subtypes present may provide a novel therapeutic target for newly
      developed ET antagonists. METHODS: Saturation, competition, and autoradiographic
      studies were performed with the subtype-specific radioligands 125I-PD151242 and
      125I-BQ3020, to characterize the ET(A) and ET(B) receptors present in NCC, MNG,
      and GBM. RESULTS: NCC expresses high-affinity ET(A) receptors on pial and
      intraparenchymal vessels and high-affinity ET(B) receptors on glia and neurons.
      MNGs express mainly (85%) high-affinity ET(A) receptors in a diffuse pattern,
      whereas GBMs express high-affinity ET(A) receptors on the neovasculature and
      ET(B) receptors on the nonvascular elements. The ET antagonist PD156707 (Kd =
      0.059 nmol/L) showed a higher affinity for the ET(A) receptor subtype than did
      bosentan (Kd = 1.1 nmol/L). CONCLUSION: ET(A) receptors are expressed in high
      concentrations in MNGs and in the vasculature of NCC and GBMs. The ET(A)
      selective antagonist PD156707 may be of potential therapeutic value in vascular
      and neoplastic diseases of the central nervous system.

PMID- 9766318
TI  - Consistent injury in the striatum of C57BL/6 mice after transient bilateral
      common carotid artery occlusion.
AB  - OBJECTIVE: The recent availability of transgenic mice enables us to study the
      functional role of single gene products in cerebral ischemia. To establish an
      experimental murine model of transient forebrain ischemia, this study examined
      the temporal profile of ischemic neuronal damage in the striatum after bilateral
      common carotid artery occlusion. METHODS: C57BL/6 mice, which are frequently used
      for genetic manipulations, were subjected to 15-minute bilateral common carotid
      artery occlusion. Ischemic injury was examined (4, 8, 24, 48, and 96 h after
      reperfusion) by Nissl staining, terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate-biotin nick-end-labeling, and nuclear staining with
      Hoechst 33258 dye. RESULTS: Regional cerebral blood flow was decreased to 11 +/-
      6% of control values during the ischemic insult. Striatal injury was observed in
      95% of animals examined after 15-minute bilateral common carotid artery
      occlusion. The number of small and medium-size neurons in the striatum was
      significantly (P < 0.05) decreased 8 hours after reperfusion and continued to
      decrease until 96 hours, whereas the number of large neurons remained constant.
      Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin
      nick-end-labeling-positive cells appeared in the dorsomedial region of the
      striatum 48 hours after the ischemic insult and throughout the striatum 96 hours
      after the ischemic insult. Brain sections stained with Hoechst 33258 dye also
      demonstrated apoptotic nuclei 96 hours after the ischemic insult. CONCLUSION:
      Striatal injury after transient forebrain ischemia is reproducible in C57BL/6
      mice and is a good model to study the molecular mechanisms of ischemic injury,
      including delayed neuronal death, using transgenic mice.

PMID- 9766319
TI  - Immunohistochemical localization of tissue plasminogen activator in vascular
      endothelium of stroke-prone regions of the rat brain.
AB  - OBJECTIVE: Tissue plasminogen activator (tPA), a major regulator of fibrinolysis,
      is present in cerebrovascular endothelium. We have suggested that local
      regulation of tPA synthesis and release in brain microcirculation could be
      important determinants of the degree of damage after cerebral ischemia. In this
      study, the normal distribution of tPA antigen was determined in several stroke
      prone regions in the rat brain often used to study the pathophysiological
      consequences of cerebral ischemia. METHODS: Immunohistochemistry and Western blot
      analysis were performed using an antibody that detects free tPA antigen and tPA
      complexed to its rapid inhibitor, plasminogen activator inhibitor-1 (PAI-1).
      Staining for von Willebrand factor, a brain endothelial cell marker, served as a
      positive control. RESULTS: Relative to von Willebrand factor, 8.6, 13, 11.4, and
      20.4% of vessels in the parietal cortex, frontal cortex, striatum, and
      hippocampus, respectively, were tPA-positive. The majority of tPA-positive
      vessels (58-75%) were classified as precapillary arterioles and postcapillary
      venules (7-20 microm), whereas capillaries (4-7 microm) and small arterioles and
      venules (20-40 microm) accounted for 11 to 22% and 11 to 19%, respectively, of
      tPA-positive vessels. Western blot analysis of brain microvascular proteins
      confirmed the presence of free tPA (67 kDa) and a stronger band representing tPA
      PAI-1 complexes. CONCLUSION: The tPA-containing cerebrovascular endothelium is
      distributed mainly in smaller vessels. In addition to the free pool of tPA, a
      large portion of tPA is complexed to PAI-1 and is therefore functionally
      inactive. The size of the free tPA cerebrovascular pool may be regulated by PAI
      1, which in turn could suppress fibrinolysis in the cerebral microcirculation.

PMID- 9766320
TI  - The history of neurological surgery at Northwestern University.
AB  - The residency program in neurological surgery at Northwestern University was
      founded in 1924 by Loyal Davis and was formally accredited by the American Board
      of Neurological Surgery in 1946. Allen Kanavel, mentor to Davis, was one of the
      original members of the Society of Neurological Surgeons. Five individuals have
      served as chief of neurosurgery at Northwestern: Davis, Paul Bucy, Anthony
      Raimondi, Albert Butler, and H. Hunt Batjer. Davis was the first surgeon west of
      the Appalachians to limit his work to neurosurgery. Between 1954 and 1963, there
      were two independent neurosurgery residency programs at Northwestern, one headed
      by Davis and the other by Bucy. A master surgeon and superb teacher, Bucy trained
      more than 65 residents and became one of the greatest authors and leaders in the
      field of neurosurgery. Neurosurgical training at Northwestern has traditionally
      emphasized excellence of patient care, strong resident and student teaching, and
      basic science research. Through the years, a major strength of the program has
      been its clinical volume and diversity. Four hospitals have played major roles in
      the program: Northwestern Memorial Hospital (created by the merger of Chicago
      Wesley Memorial Hospital and Passavant Memorial Hospital), Children's Memorial
      Hospital, Evanston Hospital, and the Veterans Administration Lakeside Hospital.
      This article traces the development of neurological surgery at Northwestern, with
      an emphasis on its historical background and the contributions of Kanavel, Davis,
      and Bucy. The present philosophy and structure of the training program and the
      program's future under the direction of Batier are also described.

PMID- 9766321
TI  - Carotid-coronary artery bypass graft conundrum.

PMID- 9766322
TI  - Extrapontine myelinolysis and behavioral change after transsphenoidal pituitary
      surgery: case report.
AB  - OBJECTIVE AND IMPORTANCE: Rapid correction of hyponatremia is considered the
      usual cause of central pontine myelinolysis and extrapontine myelinolysis. Little
      has been reported about mental changes associated with this disorder or its
      occurrence after transsphenoidal surgery. CLINICAL PRESENTATION: A 24-year-old
      woman suddenly developed markedly abnormal behavior associated with rapid
      correction of hyponatremia 11 days after undergoing transsphenoidal surgery for a
      prolactin-secreting pituitary adenoma. INTERVENTION: Magnetic resonance imaging
      and positron emission tomography with 18F-fluorodeoxyglucose showed bilateral
      caudate nuclei and putaminal lesions. Gradual, complete clinical resolution
      preceded the resolution that was revealed by magnetic resonance imaging.
      CONCLUSION: We emphasize the importance of cautious correction with frequent
      electrolyte determinations and attention to behavioral changes in the management
      of delayed hyponatremia after pituitary tumor surgery.

PMID- 9766323
TI  - Cervical actinomycosis causing spinal cord compression and multisegmental root
      failure: case report and review of the literature.
AB  - OBJECTIVE AND IMPORTANCE: Epidural invasion and the resulting cord compression
      are clinical entities not usually associated with actinomycosis, and we found
      only 11 reported cases of cord compression caused by Actinomyces infection in the
      literature. Only one reported case was described as actinomycosis with epidural
      granuloma (14, 16), whereas in the other cases, epidural macroabscess (phlegm)
      formation caused the symptoms. Histopathological demonstration of the
      inflammatory granulation tissue and gram-positive sulfur-containing filamentous
      bacteria are important for the diagnosis of actinomycosis, because the clinical
      and microbiological studies cannot always demonstrate the causative microorganism
      and primary infection source. CLINICAL PRESENTATION: In this article, a case of
      Actinomyces infection causing cervical cord compression is presented. Precise
      diagnosis was accomplished using specific histopathological studies of the
      surgical specimens; such a precise diagnosis cannot always be achieved using
      preoperative investigations and microbiological studies. The treatment modalities
      and the patient's outcome are also discussed. CONCLUSION: As shown by hematoxylin
      and eosin stain, in contrast to the Nocardia species, Actinomyces filaments
      histopathologically are basophilic in nature and terminate in eosinophilic clubs
      as a predictive feature. The clinical and radiological findings closely resemble
      metastatic tumors and other infectious processes. A differential diagnosis is
      also emphasized in this article, along with a review of the literature.

PMID- 9766324
TI  - Cervical arachnoid cysts after craniocervical decompression for Chiari II
      malformations: report of three cases.
AB  - OBJECTIVE AND IMPORTANCE: We describe three cases in which ventrally situated
      cervical arachnoid cysts led to spinal cord or cervicomedullary compression after
      repeat craniocervical decompression for Chiari II malformations. CLINICAL
      PRESENTATION: All three patients underwent craniocervical decompression when
      their Chiari malformations became symptomatic. The first patient developed
      chronic vertiginous spells and headache and was treated with repeated
      craniocervical decompression procedures during several years. Seven months after
      undergoing her third decompression procedure, she developed severe dizzy spells,
      which were determined to be of brain stem origin. The second patient had a small,
      asymptomatic arachnoid cyst anterior to the brain stem discovered at age 6 years.
      After undergoing repeat craniocervical decompression for headaches 8 years after
      undergoing his first procedure, the patient developed severe neck pain and acute
      quadraparesis. A third patient underwent repeat craniocervical decompression at
      age 14 years for cranial nerve dysfunction. Postoperatively, he acutely developed
      paresis of extraocular movements and incoordination of the upper extremities. All
      three patients were found to have anteriorly situated arachnoid cysts compressing
      the brain stem and/or cervical spinal cord. INTERVENTION AND TECHNIQUE:
      Fenestration of the arachnoid cyst or drainage with cystoperitoneal shunting
      adequately treated acute brain stem or cervical spinal cord compression. All
      three patients had achieved satisfactory relief from their acute symptoms of
      neural compression at their follow-up examinations. CONCLUSION: An association
      between spinal arachnoid cysts and neural tube defects has previously been
      reported. However, the development of previously undetected spinal arachnoid
      cysts after craniocervical decompression was unexpected. We hypothesize that
      extensive craniocervical decompression may alter the cerebrospinal fluid pressure
      dynamics in such a way that the anterior subarachnoid space, previously
      compressed, may dilate. Occasionally, because of perimedullary arachnoiditis, the
      cerebrospinal fluid may become loculated and act as a mass. Direct fenestration
      or shunting may successfully treat this problem, and less extensive
      craniocervical decompression may avoid it.

PMID- 9766325
TI  - Syringomyelia persistence after Chiari decompression as a result of
      pseudomeningocele formation: implications for syrinx pathogenesis: report of
      three cases.
AB  - OBJECTIVE AND IMPORTANCE: We present the cases of three patients in whom
      pseudomeningocele (PSM) formations after posterior fossa decompression of
      hindbrain herniations (Chiari I malformations) were associated with persistence
      of syringomyelia. The physiological importance of correcting this complication
      has not been previously described. CLINICAL PRESENTATION: We identified three
      patients who developed suboccipital PSMs after undergoing posterior fossa
      decompression for hindbrain herniations and syringomyelia. All three patients
      experienced persistence of their symptoms and their syringomyelia, despite
      adequate posterior fossa decompression. TECHNIQUE: Subsequent exploration
      revealed cerebrospinal fluid leaking either from the dural suture line (one
      patient) or from perforations found within the bed of a polyglactin mesh dural
      graft (two patients). Correction of the PSM resulted in resolution of both the
      syringomyelia and the symptoms in all three patients. DISCUSSION: The persistence
      of syringomyelia in the presence of a PSM may be the result of dissipation of the
      cerebrospinal fluid systolic pressure wave into the distensible PSM cavity. This
      phenomenon suggests that the cerebrospinal fluid pressure exerted on the spinal
      cord surface favors resolution of the syrinx cavity.

PMID- 9766326
TI  - Nocardia abscess of the choroid plexus: clinical and pathological case report.
AB  - OBJECTIVE: Cerebral Nocardia abscesses are rare, accounting for approximately 1
      to 2% of all cerebral abscesses. Prompt aggressive surgical treatment involving
      craniotomy and excision of these lesions has been advocated by many authors,
      because these lesions have significantly higher morbidity and mortality rates
      than do most other cerebral abscesses. We report an atypical presentation of
      cerebral nocardiosis localized to the choroid plexus of the lateral ventricle.
      CLINICAL PRESENTATION: A 56-year-old man presented with a 3-week history of
      fever, cough, and progressive headache and an ensuing 3-day history of
      progressive lethargy, confusion, and gait ataxia. Radiographic studies
      demonstrated a loculated contrast-enhancing left lateral ventricular lesion with
      significant perilesional parenchymal edema that was thought preoperatively to be
      a neoplasm. INTERVENTION: The patient underwent a craniotomy for resection of the
      lesion. Intraoperatively, a reddish gray lesion with purulent exudate was
      encountered within the left lateral ventricle intimately adherent to the choroid
      plexus as well as to the ependyma and subependymal veins. A frozen section
      demonstrated an organizing abscess wall. The lesion was resected in its entirety,
      and multiple cultures were sent for analysis. CONCLUSION: Microbiology cultures
      grew Nocardia asteroides. A course of intravenous antibiotics was started, which
      included trimethoprim-sulfamethoxazole, amikacin, and ceftriaxone. Two weeks
      after surgery, at the time of discharge, the patient's neurological status had
      improved considerably. Although Nocardia abscesses have been documented to occur
      throughout the central nervous system, the presentation of a lesion confined to
      the choroid plexus of the lateral ventricle with significant parenchymal edema is
      unusual and demonstrates that Nocardia abscesses must be considered in the
      differential diagnosis of a contrast-enhancing intraventricular mass lesion
      involving the choroid plexus.

PMID- 9766327
TI  - Failure of hydroxyapatite cement to set in repair of a cranial defect: case
      report.
AB  - OBJECTIVE AND IMPORTANCE: Hydroxyapatite cement, a new biomaterial that is being
      marketed as a method for reconstructing cranial defects, offers many advantages.
      We document, herein, the complete dissolution and failure of this material to set
      in a surgically dry field, under optimal conditions, an occurrence that has not
      been previously reported. CLINICAL PRESENTATION: Hydroxyapatite cement was used
      for reconstruction of a frontal bone defect secondary to a traumatic depressed
      cranial fracture in a 9-year-old male patient. At the time of suture removal on
      postoperative Day 6, we observed serous discharge from the wound, a reappearance
      of the cranial defect, and brain pulsations visible subcutaneously. INTERVENTION:
      The patient was returned to the operating room, at which time we learned that the
      hydroxyapatite cement had migrated out of the defect; small concretions of the
      cement were scattered throughout the subgaleal space. The concretions of cement
      in the subgaleal space and the small amount of cement remaining in the defect
      were removed, and titanium mesh was used. An excellent cosmetic result was
      achieved. CONCLUSION: Although offering many advantages, hydroxyapatite cement
      does carry a risk of failure to set, despite optimal technique. Causes for
      failure to set, as well as possible modifications in the use of material and
      technique, are discussed.

PMID- 9766328
TI  - Primary stenting of the extracranial internal carotid artery in a patient with
      multiple cervical dissections: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: Spontaneous dissection of the extracranial internal
      carotid artery (ICA) and vertebral artery (VA) is a well-documented cause of
      stroke in young, previously healthy patients. The majority of patients with
      spontaneous dissection are successfully treated with antiplatelet or
      anticoagulation therapy, but a significant proportion of patients progress to
      suffer devastating morbidity and mortality. Surgical intervention has primarily
      consisted of proximal ligation, extracranial-intracranial bypass, or
      endarterectomy. Generally, these procedures are technically demanding and yield
      disappointing clinical results. CLINICAL PRESENTATION/INTERVENTION: A 36-year-old
      man without a significant medical history initially presented with a several-day
      history of episodic right upper extremity weakness and numbness and visual
      obscurations. Cerebral angiography revealed bilateral ICA long segment narrowing
      (95%), distal left VA high-grade (95%) stenosis compatible with dissections, and
      right VA proximal occlusion. While therapeutically anticoagulated on heparin, the
      patient continued to experience crescendo episodes of right upper extremity
      paresis and paresthesias as well as aphasia. The patient underwent primary
      stenting of the left ICA, using a series of six overlapping stents (three
      Gianturco-Roubin coronary stents and three Palmaz-Schatz coronary stents). The
      patient remained symptom-free without neurological complications, and subsequent
      angiography performed at the 9-month follow-up examination confirmed continued
      patency of the stented left ICA as well as recanalization of the right ICA and
      VA. CONCLUSION: Neurovascular stents offer a minimally invasive and potentially
      efficacious treatment for the prevention of cerebral ischemia in patients with
      spontaneous extracranial dissection who remain symptomatic despite therapeutic
      anticoagulation.

PMID- 9766329
TI  - Reversibility of severe sagittal sinus thrombosis with open surgical thrombectomy
      combined with local infusion of tissue plasminogen activator: technical case
      report.
AB  - OBJECTIVE: To explore the controversial issue of anticoagulant therapy and
      indications for surgery in association with severe sinus thrombosis. METHODS:
      During the last 4 years, we have treated three patients with severe sinus
      thrombosis of the dural sinuses. All three patients received systemic
      anticoagulant therapy and, after experiencing neurological deterioration,
      underwent open thrombectomy and local thrombolysis. After the operation,
      aggressive intensive care was given and included cerebral perfusion monitoring,
      barbiturate administration, hyperventilation, and osmotherapy. The treatment was
      guided by repeated neuroradiological investigations. RESULTS: All three patients
      returned to their normal lives. CONCLUSION: Intracranial sinus thrombosis, even
      in the worst neurological state, should be treated aggressively. A cornerstone in
      treatment is systemic anticoagulant therapy and repeated neuroradiological
      studies. When, despite adequate anticoagulant therapy and intensive care,
      neurological deterioration occurs, a combination of open thrombectomy and local
      thrombolytic therapy should be considered.

PMID- 9766330
TI  - Traumatic intraventricular hemorrhage treated with intraventricular recombinant
      tissue plasminogen activator: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: Traumatic intraventricular hemorrhage (IVH) can result
      in association with acute obstructive hydrocephalus, repetitive malfunction of
      external ventricular drains (EVDs), and uncontrollable increased intracranial
      pressure. We report a case showing the safe and effective use of intraventricular
      recombinant-tissue plasminogen activator in a child with severe brain injury and
      acute hydrocephalus from IVH. CLINICAL PRESENTATION: A 15-year-old male patient
      presented to us after a motor vehicle accident with bilateral extensor posturing,
      intracerebral and IVH, and acute obstructive hydrocephalus. INTERVENTION: A right
      EVD was placed and functioned only transiently. A left EVD was placed and
      functioned only transiently. Because of the inability to maintain ventricular
      drainage, rising intracranial pressure, and worsening clinical status, 5 mg of
      recombinant-tissue plasminogen activator was injected through each EVD. Excellent
      EVD function was obtained quickly, with control of intracranial pressure and
      improvement in clinical status and without hemorrhagic complication. CONCLUSION:
      With obstructive hydrocephalus secondary to acute traumatic IVH that cannot be
      controlled with EVD because of recurrent obstruction from intraventricular blood,
      intraventricular recombinant-tissue plasminogen activator can be effective and
      safe, despite preexisting multiple hemorrhagic intracranial injuries.

PMID- 9766331
TI  - Use of preoperative computed tomography-angiography in cranial remodeling:
      technical note.
AB  - OBJECTIVE/IMPORTANCE: One of the most severe complications of craniosynostosis
      repair is dural sinus laceration. Massive hemorrhage and air embolism are
      potentially life-threatening sequelae that can result from such an event. The
      aberrant anatomy of patients with craniosynostosis only accentuates this risk,
      because separation of the calvaria from the underlying dura is often performed
      without direct visualization of the sinuses. METHODS: Three-dimensional computed
      tomography was combined with computed tomographic angiography in the preoperative
      assessment of patients with craniofacial abnormalities. RESULTS: A clear
      understanding of the dural sinus anatomy in relation to the overlying bony
      landmarks became available to the operating surgeon. Six patients underwent this
      procedure, with excellent visualization of the bony and sinus anatomy achieved in
      all cases. CONCLUSION: It is thought, that the benefit of combining these
      procedures has been significant by allowing the visualization of the dural sinus
      anatomy and overlying bony landmarks. This procedure conveys minimal concomitant
      morbidity or expense to the patient, yet offers valuable insight toward operative
      planning and complication avoidance.

PMID- 9766332
TI  - Library: historical perspective. Herbert Olivecrona (1891-1980)

PMID- 9766335
TI  - The twelfth labor of Heracles.

PMID- 9766336
TI  - Elastin degradation in the superficial temporal arteries of patients with
      intracranial aneurysms reflects changes in plasma elastase.

PMID- 9766337
TI  - The Ray Threaded Fusion Cage for posterior lumbar interbody fusion.

PMID- 9766338
TI  - Visual impairment associated with mutism after posterior fossa surgery in
      children.

PMID- 9766339
TI  - Enterogenous cyst of the fourth ventricle: case report.

PMID- 9766340
TI  - The Lipoprotein and Coronary Atherosclerosis Study (LCAS) in context: assessing
      the benefits of lipid-lowering therapy. Introduction.

PMID- 9766341
TI  - Assessing the benefits of lipid-lowering therapy.
AB  - In recent years, a substantial body of evidence has emerged to support the use of
      lipid-lowering therapy in the prevention of coronary artery disease, and many
      physician groups have endorsed the management of dyslipidemia in at-risk
      patients. An important consideration in such endorsements has been the issue of
      the safety of lipid intervention; many early primary- and secondary-prevention
      studies reported either no reduction in all-cause mortality rates or an increase
      in non-coronary artery disease mortality rates in treated patients. These
      observations raised serious concerns about the safety of such therapy. However, 2
      landmark studies, the Scandinavian Simvastatin Survival Study (4S) and the West
      of Scotland Coronary Prevention Study (WOSCOPS), have contributed greatly to
      alleviating these concerns. In this article, a review of the epidemiologic
      evidence supporting the use of lipid modification will be presented, including
      important trials and meta-analyses, and the cost-effectiveness of lipid-modifying
      treatment will be discussed.

PMID- 9766342
TI  - Clinical trial endpoints: angiograms, events, and plaque instability.
AB  - Clinical trials provide evidence on methods for risk assessment of coronary
      artery disease and on interventions used to decrease risk. Plaque rupture, which
      leads to either progression of coronary artery disease or myocardial infarction,
      is the critical biologic event in the pathophysiology of atherothrombosis that
      leads to morbidity and mortality. Trials with endpoints of myocardial infarction
      and death provide direct information on the effect of intervention on morbidity
      and mortality, but these trials require extremely large sample sizes and long
      duration. To obtain clinical information more quickly and with fewer patients,
      investigators have conducted trials using surrogate endpoints that examine the
      effect of treatment on the underlying disease process through measures of
      atherosclerotic lesion progression and/or regression and new lesion development.
      Coronary angiography studies have consistently shown that lipid-modifying therapy
      decreases coronary artery disease progression. The correlation between rate of
      progression of coronary artery disease and clinical coronary events such as
      myocardial infarction and coronary death may be explained by the relation of both
      to the biologic process of plaque rupture and thrombosis.

PMID- 9766343
TI  - Coronary arteriography and lipid lowering: limitations, new concepts, and new
      paradigms in cardiovascular medicine.
AB  - Coronary arteriography has played a central role in improving our understanding
      of the mechanisms of unstable coronary syndromes and the benefits of cholesterol
      lowering. However, coronary arteriography as currently used is outmoded and
      inadequate for new clinical algorithms based on vigorous lipid and other risk
      factor control as alternatives to invasive procedures for the primary treatment
      of coronary artery disease. What is needed is a way of viewing or analyzing
      noninvasive myocardial perfusion images and coronary arteriograms so as to
      identify and quantify the extent or severity of diffuse coronary atherosclerosis.
      Determining the relative contribution of diffuse and segmental narrowing by
      definitive myocardial perfusion imaging or coronary arteriography would provide
      the optimal basis for determining the need for revascularization procedures. In
      the absence of significant segmental stenoses, mild or diffuse disease identified
      by coronary arteriography would also provide a definitive diagnosis as the basis
      for lifelong cholesterol-lowering drugs and risk factor modification, even for
      patients with normal cholesterol levels. Thus, it is important to consider
      several new concepts for analyzing coronary arteriograms. More physiologically
      accurate invasive and noninvasive technology allows improved diagnosis and
      management of coronary atherosclerosis as new paradigms in cardiovascular
      medicine.

PMID- 9766344
TI  - Relation of clinical benefit to metabolic effects in lipid-lowering therapy.
AB  - Studies of lipid-modifying therapy show that inhibition of cholesterol synthesis
      is required in at least 2 sites-in hepatic cells and in cells located in the
      walls of coronary arteries-if the progression of coronary atherosclerosis is to
      be decreased in patients with relatively normal levels of low-density lipoprotein
      (LDL) cholesterol. This is clinically important, because the majority of patients
      with coronary artery disease do not have severely elevated LDL cholesterol
      levels. Of the 2 angiographic trials of 3-hydroxy-3-methylglutaryl coenzyme A
      (HMG CoA) reductase inhibitors ("statins") in patients with coronary artery
      disease and average cholesterol levels, only the Lipoprotein and Atherosclerosis
      Study (LCAS) of fluvastatin reported slowed angiographic progression of coronary
      artery disease in these patients. The change in LDL cholesterol levels during
      treatment with fluvastatin did not predict the extent of change in coronary
      atherosclerosis or incidence of clinical cardiac events. Apparently, the
      metabolic effects of treatment with fluvastatin were more important than the
      extent to which blood cholesterol levels were lowered. The clinical benefits of
      treatment with statins should be directly compared in randomized controlled
      clinical trials among patients with average cholesterol levels.

PMID- 9766345
TI  - Economic implications of lipid-lowering trials: current considerations in
      selecting a statin.
AB  - Little doubt remains about the value of lipid-lowering therapy since publication
      of the results of large, randomized, controlled trials that show decreased total,
      as well as coronary, mortality with the use of statins for primary and secondary
      prevention of coronary artery disease. All of the available statins are effective
      and safe, but they vary greatly in terms of cost-effectiveness. Fluvastatin has
      been determined to be a cost-effective therapeutic agent in the large proportion
      of the population with mild-to-moderate dyslipidemia who fit treatment guidelines
      of the National Cholesterol Education Program (NCEP). Atorvastatin and
      simvastatin are cost-effective for the relatively smaller number of patients who
      require greater reductions in cholesterol.

PMID- 9766346
TI  - Future of lipid-lowering trials: what else do we need to know?
AB  - Convincing clinical trial evidence shows that lipid-lowering therapy can be
      effective in primary and secondary prevention of coronary artery disease events.
      At least 2 studies indicate that this benefit extends to persons with only mild
      or moderate hypercholesterolemia. The benefits of lipid-lowering therapy in
      certain subpopulations, however, remains to be elucidated. The effects in women,
      African Americans, the elderly, and patients with concomitant coronary artery
      disease risk factors such as diabetes and hypertension are only recently being
      studied in large, well-designed trials. Other trials, described herein, are
      studying the benefits of therapy in persons with coronary artery disease and low
      levels of high-density lipoprotein (HDL) cholesterol (but normal or only mildly
      elevated total or low-density lipoprotein [LDL] cholesterol). Future trials are
      needed to assess prospectively the value of aggressive lipid-lowering therapy on
      coronary artery disease events in diabetic patients with and without coronary
      artery disease. New drug therapies and innovative uses for existing therapies are
      being developed that may have an important impact on the prevention of coronary
      artery disease.

PMID- 9766347
TI  - Congenital diaphragmatic hernia: developing a protocolized approach.
AB  - BACKGROUND/PURPOSE: The purpose of this study was to evaluate the evolving
      outcome of newborns who have congenital diaphragmatic hernia (CDH) using a
      protocolized approach to management, which includes extracorporeal membrane
      oxygenation (ECMO) and to present the details of such a management protocol.
      METHODS: A retrospective chart review was conducted of the neonatal outcome of
      near-term (>34 weeks' gestation) newborns with CDH all referred to the Royal
      Alexandra Hospital either before or after delivery. A protocol was developed that
      included antenatal assessment, the use of antenatal steroids, planned delivery,
      use of prophylactic surfactant, pressure limited gentle ventilation, permissive
      hypercarbia and hypoxia, and venovenous ECMO, if indicated. RESULTS: Sixty-five
      infants with CDH were treated from February 1989 through August 1996. Twenty
      three infants were inborn, 20 of whom were antenatal referrals. Overall, 51 of
      the 65 infants survived (78%). Thirteen of the 23 inborn infants survived with
      conservative management, and 10 required ECMO, of whom, eight were long-term
      survivors. Thirty-eight infants required ECMO, and 26 survived (68%), whereas
      there were only two deaths among the 27 conservatively treated infants. Eighteen
      of 20 inborn infants with an antenatal diagnosis survived, compared with 13 of 21
      (62%) outborn infants. An antenatal diagnosis before 25 weeks' gestation was
      associated with a 60% survival rate. Sixty-three percent of infants whose best
      postductal PaO2 value before ECMO was less than 100 torr survived, and 7 of 11
      infants with a best postductal PaO2 value of less than 50 torr before ECMO
      survived (64%). The average age at surgery progressively increased over time both
      for infants who did not require ECMO (1.3 days to 5.8 days; P = .01) and for
      infants who received ECMO (1.9 days to 8.2 days; P = .016). CONCLUSIONS: The use
      of a protocolized management for infants with CDH has been associated with
      improving outcome in a population at high risk. The components (either separately
      or combined) of these protocolized approaches need to be tested in prospective
      trials to determine their true benefit. In addition, there is a need to evaluate
      prospectively the outcomes of infants with CDH born in ECMO centers compared with
      those infants born in other tertiary care neonatal units to determine the most
      appropriate management of the fetus with CDH.

PMID- 9766348
TI  - Elective delayed reduction and no anesthesia: 'minimal intervention management'
      for gastrochisis.
AB  - PURPOSE: In a pilot study of 14 children, born when the authors were on a 1:5 "on
      take" for neonatal referrals, a policy evolved of elective delayed midgut
      reduction without anaesthesia or sedation in the incubator on the neonatal
      surgical unit. There was no other form of selection, and it was fortunate that
      the authors did not encountered any adverse criteria in this small series.
      METHODS: Bowel reduction, which was pain free, was undertaken conventionally with
      the same attention and with no greater difficulty than under general anesthesia.
      Delaying midgut reduction for more than 4 hours led to more stable
      cardiovascular, respiratory, and renal parameters. Moderate lower limb congestion
      cleared rapidly. RESULTS: At the end of the procedure, all children were
      conscious, and 12 were alert and indistinguishable from normal babies. A mild
      periumbilical infection developed in two patients. Eleven of the 12 surviving
      children established enteral nutrition within 11 to 32 days, eight within 18
      days. Another child with ileal atresia and bowel dilatation required bowel
      tailoring and lengthening (LILT) to allow enteral nutrition. All are physically
      and developmentally normal, and none has required umbilical herniorrhaphy or
      umbilicoplasty. All except one have a "scarless" abdomen and an aesthetically
      normal umbilicus. In marked comparison, two children immediately and obviously
      were unwell with abdominal pain, tachycardia, and metabolic acidosis. Abdominal
      wall cellulitis rapidly developed in both. At laparotomy one had a midgut
      volvulus and died at 22 months of short bowel syndrome (SBS) and the other with a
      perforated segmental ileal atresia died at 7 months of Enterobacter cloacae
      septicaemia. CONCLUSIONS: Our small study suggests that delayed midgut reduction
      without anaesthesia appears safe, carrying no additional morbidity or mortality.
      It helps avoid anaesthesia, muscle relaxants, and ventilation and has obvious
      resource benefits. The conscious child is a safety asset, and any postreduction
      deviation from a "normal, well-perfused, comfortable, and painfree" child is an
      indication for urgent laparotomy. This "minimal intervention management," when
      applicable, has become our preferred first option for children with
      gastroschisis. Further extension of this study will determine those not eligible
      for this technique and establish "exclusion criteria."

PMID- 9766349
TI  - Outcome of patients operated on for esophageal atresia: 30 years' experience.
AB  - PURPOSE: The aim of this study was to evaluate the outcome and late sequelae of
      patients with esophageal atresia or tracheoesophageal fistula. METHODS: Sixty
      patients with esophageal atresia or tracheoesophageal fistula (EA-TEF) were
      treated in Tampere University Hospital in the years 1963 through 1993. Long-term
      outcome was evaluated with a questionnaire, pulmonary and esophageal function
      test results, 24-hour pH level monitoring, tracheobronchoscopy findings, and
      esophagogastroscopy with biopsy sections and samples for bacterial cultures.
      RESULTS: One third of the respondents reported having impaired quality of life
      because of respiratory infections, dyspnea, and difficulties in swallowing and
      coughing at night. Eighteen percent had gastroesophageal reflux (GER) symptoms.
      The rate of symptoms decreased with age. Impaired pulmonary function, GER,
      abnormal esophageal peristalsis, and transit time were registered.
      Tracheobronchoscopy showed tracheal narrowing and inflammation in one third; in
      histopathologic analysis, however, the rate of inflammation was more than
      doubled. Histologically, esophageal inflammation was found in 51%, Barrett's
      esophagus in 6%, and a Helicobacter pylori infection in 21% of cases. The
      severity of GER, esophageal peristaltic abnormality, tracheal inflammation, and
      impairment of pulmonary function seems to be alleviated with age. CONCLUSIONS:
      Although the long-term outcome of EA-TEF patients seems to be favorable,
      respiratory and gastrointestinal symptoms as well as functional abnormalities
      remain frequent. Gastric metaplasia in the esophagus and the high rate of
      tracheal, esophageal, and gastric inflammation indicate a need for long-term
      follow-up.

PMID- 9766350
TI  - Laparoscopic appendectomy in children performed using single endoscopic GIA
      stapler for both mesoappendix and base of appendix.
AB  - BACKGROUND/PURPOSE: Similar to open appendectomy (OA), most of the methods
      described for laparoscopic appendectomy (LA) require two steps: (1) dissection
      and division of mesoappendix and (2) excision of appendix. Dissection of
      mesoappendix requires more skill and experience during LA. In single endoscopic
      GIA stapler laparoscopic appendectomy technique (SESLAT), both mesoappendix and
      base of appendix may be divided in one step with the application of a single
      endoscopic GIA stapler. METHODS: LA was attempted in 18 patients who had acute
      appendicitis and was successfully performed in 16 patients. RESULTS: In two
      patients, the operation was converted to OA. The authors did not need conversion
      to OA because of complication resulting from the use of the stapler. CONCLUSIONS:
      SESLAT is a quick, easy, and versatile method for LA in children that obviates
      dissection of mesoappendix and related complications. Thus, it enables LA to be
      performed by inexperienced beginners.

PMID- 9766351
TI  - Hepatocellular carcinoma in children: clinical review and comparison with adult
      cases.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) in children was rarely reported and
      usually included with hepatoblastoma in most studies of pediatric liver
      malignancies despite different clinical behaviors. The authors report their
      experience in pediatric HCC and discuss its differences from adult HCC. METHODS:
      A retrospective review of radiographic, laboratory, pathological, and therapeutic
      data in 55 children with HCC was performed. The liver function was graded by
      modified Child's classification. Kaplan-Meier survival curves in various
      therapeutic and Child's groups were plotted, and log-rank test was used to detect
      differences among survival curves. RESULTS: Although children with HCC mostly
      presented with advanced disease at diagnosis, disturbances of liver function were
      unremarkable. Sixty-eight percent of cases concurred with liver cirrhosis. The
      median survivals for resectable, chemotherapeutic, and untreated HCCs were 23, 3,
      and 2 months, respectively. Resectable HCC significantly posed a much better
      prognosis. However, the resectability was unsatisfactory (18.2%). Resection was
      limited because of anatomic unfeasibility including bilateral involvement
      (62.5%), portal vein thrombi (41.7%), distant metastasis (29.1%), para-aortic
      lymphadenopathy (18.8%), inferior vena cava thrombi (16.7%), and hilar invasion
      (6.3%). Distant metastasis was the most ominous for survival in children with
      unresectable HCC. CONCLUSIONS: HCC behaved somewhat differently between children
      and adults. Surgical resection represented the best hope of long-term survival.
      The outcome in children could not keep up with that in adults because of a
      diagnostic delay. Hence, alpha-fetoprotein and sonography screening in carrier
      children should be worthwhile.

PMID- 9766352
TI  - Pleural effusions in lymphoblastic lymphoma: a diagnostic alternative.
AB  - BACKGROUND: Children with large anterior mediastinal masses frequently present
      with severe respiratory compromise and often pose a difficult diagnostic dilemma.
      A biopsy is preferred for diagnosis before treatment can begin; however, many of
      these children are at risk of acute clinical deterioration and cardiovascular
      arrest with the induction of anesthesia. The authors noted a correlation between
      pleural effusions and lymphoblastic lymphoma and recently diagnosed three cases
      of lymphoblastic lymphoma in children with a large anterior mediastinal mass and
      pleural effusion through cytological and flow cytometric examination of the
      pleural fluid. METHODS: To focus on this problem, 101 pediatric patients
      presenting with an anterior mediastinal mass between January 1980 and September
      1994 were reviewed to determine if pleural effusions occur more frequently at
      initial presentation with lymphoblastic lymphoma than with Hodgkin's disease,
      thus offering a means of diagnosis in children with severe respiratory
      compromise. The patients' chest radiographs and/or computed tomograms for the 88
      cases in which they were available were reviewed retrospectively in a blinded
      fashion to identify those children with pleural effusions at the time of
      presentation. RESULTS: In this study, 71% of patients with lymphoblastic lymphoma
      (10 of 14) had a pleural effusion at presentation, whereas only 11.7% of patients
      with Hodgkin's disease (7 of 60) had a pleural effusion on initial presentation.
      (P < .002 Fisher's Exact test). CONCLUSION: This retrospective review suggests
      that there is a significantly greater association of pleural effusions in
      patients with lymphoblastic lymphoma than with Hodgkin's disease. Our experience
      supports the conclusion that thoracentesis may provide a means of diagnosis in
      children presenting in severe respiratory compromise obviating the need for
      anesthesia and open biopsy.

PMID- 9766353
TI  - Hypoxic pulmonary vasoconstriction is impaired in rats with nitrofen-induced
      congenital diaphragmatic hernia.
AB  - BACKGROUND: Pulmonary hypertension and persistent fetal circulation contribute to
      the high mortality rate associated with congenital diaphragmatic hernia (CDH).
      Morphological alterations of the pulmonary vasculature in infants with CDH are
      thought to contribute to exaggerated vasoconstrictor responses to normal
      vasoconstrictor stimuli. In the pulmonary circulation, hypoxia is a potent
      vasoconstrictor. Under pathological conditions, hypoxia-induced vasoconstriction
      may contribute to the development of pulmonary hypertension. METHODS: The authors
      have used the nitrofen-induced model of congenital diaphragmatic hernia in rats
      to investigate the magnitude of the hypoxic vasoconstrictor response. Congenital
      diaphragmatic hernias were induced in fetal rats by feeding nitrofen (2,4
      dichlorophenyl-p-nitrophenyl ether) to pregnant Sprague-Dawley rats at
      midgestation. Hypoxia-induced vasoconstriction was measured in isolated, perfused
      third-generation pulmonary arterioles from normal rats and from rats with
      nitrofen-induced CDH. RESULTS: The hypoxic vasoconstrictor response was
      significantly blunted in the pulmonary arterioles of fetal rats with nitrofen
      induced (2% +/- 1% vasoconstriction), as compared with the responses observed in
      normal fetal rats (15% +/- 3% vasoconstriction, P = .004). CONCLUSION: Blunting
      of the hypoxic pulmonary vasoconstrictor response may contribute to ventilation
      perfusion mismatching in infants with CDH.

PMID- 9766354
TI  - Gastric tubes in children with caustic esophageal injury: a 32-year review.
AB  - PURPOSE: Caustic injury to the upper aerodigestive system with scarring of the
      pharynx, hypopharynx, and esophagus is a challenging reconstructive problem. The
      author has used the gastric tube for this purpose for three decades. METHODS:
      During the last 32 years (1965 to 1996 inclusive) the author treated 11 patients
      who required esophageal replacement with a gastric tube conduit, which was
      anastomosed to the cervical esophagus. At the time of injury, ages ranged from 2
      months to 13 years (mean, 3 years) in seven boys and four girls. Time from injury
      to esophageal replacement was 12 months to 14 years (mean, 5 years). All 11 had
      multiple dilations before the replacement. Two had injury and scarring of the
      epiglottis and larynx that required pharyngeal reconstruction and tracheostomy
      before replacement. Nine patients underwent reconstruction with a gastric tube
      anastomosed to the cervical esophagus, and the other two had an interposition
      with an intrathoracic anastomosis. Eight tubes were antiperistaltic and three
      isoperistaltic. Seven tubes were placed in the retrosternal space, three were
      transthoracic, and one was subcutaneous. Six tubes were completed in two stages
      and five in a single stage. RESULTS: Nontube complications were wound infection
      (n = 2), perforation (n = 2), paralyzed hemidiaphragm (n = 1), and recurrent
      laryngeal nerve injury requiring tracheostomy (n = 1). Tube complications were
      anastomotic leak (n = 9), stricture (n = 8), anastomotic resection (n = 3), ulcer
      (n = 1), and perforation (n = 1). Six required posttube multiple dilations for
      several years including self-bouginage (n = 2). All learned to swallow and eat
      initially with minimal aspiration; only one remains on tube feed supplements.
      Long-term follow-up (3 to 30 years) includes nine eating normally and not
      requiring dilations (the tracheostomy boy has chronic lung disease), one lost to
      follow-up after 1 year, and one death from tube hemorrhage 2 months after
      operation. CONCLUSION: Children with caustic injury to the upper aerodigestive
      system can undergo gastric tube replacement with good results. The majority of
      the problems relate to the esophagogastric tube anastomosis.

PMID- 9766356
TI  - An evidenced-based clinical pathway for acute appendicitis decreases hospital
      duration and cost.
AB  - BACKGROUND/PURPOSE: In the pediatric population, appendicitis remains the most
      common surgical emergency encountered. The purpose of this study was to determine
      the impact of an evidence-based clinical pathway for acute appendicitis on
      patient care as well as hospital and home care costs at the authors' pediatric
      institution. METHODS: A prospective evaluation was conducted of an appendicitis
      clinical pathway (June 1996 through November 1996) compared with historical
      control patients (June 1994 through November 1994) not cared for by the pathway.
      RESULTS: Data (average +/- SD) for 120 pathway (P) patients were compared with
      122 control (C) patients. Age (11.5 +/- 3.6 years for C v 11.2 +/- 3.9 years for
      P), rates of negative appendectomy (12.3% for C v 9.2% for P) and perforation
      (26.2% for C v 18.3% for P) were similar. Pathway patients with nonperforated
      appendicitis were more often discharged from the hospital within 24 hours (48%
      for C v 67% for P; P = .014) with lower hospital costs ($4,095 +/- $1,280 for C v
      $3,638 +/- $1,633 for P; P = .001). Pathway patients with perforated appendicitis
      had shorter hospitalization (185.2 +/- 59 hours for C v 113 +/- 44 hours for P; P
      = .0001) and lower hospital costs ($11,175 +/- $3,893 for C v $7,823 +/- $2,366
      for P; P = .0001). CONCLUSION: An evidence-based appendicitis pathway decreased
      duration of hospitalization and cost without adversely affecting diagnosis or
      therapy. Clinical pathways for surgical diagnoses may prove useful as a means to
      minimize costs without compromising patient care.

PMID- 9766355
TI  - Pulmonary arterioles from rats with congenital diaphragmatic hernias are
      hypoplastic but not hyperresponsive.
AB  - BACKGROUND: Infants born with congenital diaphragmatic hernias (CDH) frequently
      die as a result of pulmonary hypertension and persistent fetal circulation. The
      pulmonary vessels of infants with CDH have decreased total cross-sectional area,
      increased muscle content, and muscularization of intra-acinar arterioles that are
      normally not muscularized. These structural alterations are believed to result in
      exaggerated responses to normal vasoconstrictor stimuli. METHODS: The authors
      used the nitrofen-induced CDH model in rats to determine whether the
      vasoconstrictor responses of pulmonary arterioles are exaggerated in this animal
      model of CDH. The authors compared the responses of isolated third-generation
      pulmonary arterioles from normal rats and from rats with nitrofen-induced CDH to
      K+-induced depolarization, phenylephrine, angiotensin II, serotonin, and the
      thromboxane A2 agonist, U46619. RESULTS: It was found that the intraluminal
      diameter of third-generation pulmonary arterioles from CDH rats was significantly
      less than in controls (129 +/- 5 micron v 152 +/- 9 micron, respectively). In
      addition, the ratio of wall thickness to vessel internal diameter was increased
      in the third-generation pulmonary arterioles of rats with nitrofen-induced CDH
      (0.62 +/- 0.4 v 0.50 +/- 0.5 for controls). Responses to K+-induced
      depolarization, phenylephrine, angiotensin II, serotonin, and U46619, however,
      were not different for pulmonary arterioles from control and CDH rats.
      CONCLUSION: These data suggest that the structural alterations of the pulmonary
      vasculature observed in infants with CDH may not cause exaggerated
      vasoconstrictor responses to normal vasoconstrictor stimuli.

PMID- 9766357
TI  - Antenatally diagnosed surgical anomalies: the psychological effect of parental
      antenatal counseling.
AB  - BACKGROUND: Increasing numbers of infants have the diagnosis of a surgical
      malformation made before birth. This allows (1) fetal intervention, (2) in utero
      transfer and planned delivery in a surgical center, and (3) antenatal counseling
      of likely prognosis and outcome. The aim of this study was to assess the
      effectiveness of antenatal counseling in terms of the parental psychological
      response. METHODS: Antenatal counseling by a pediatric surgeon and neonatal nurse
      was given after ultrasound diagnosis of a fetal surgical malformation (eg,
      gastroschisis, diaphragmatic hernia). Anxiety levels were measured using the
      Spielberger State-Trait Anxiety Inventory, a tool used by psychologists to assess
      the inherent level of anxiety, or Trait anxiety (STAI-T), and the current level
      of anxiety, or State anxiety (STAI-S). RESULTS: Fifty six prospective mothers
      filled out Spielberger questionnaires (subjects, n = 26; controls, n = 30).
      Nineteen subjects' partners also completed questionnaires. There was no
      significant difference in Trait anxiety scores between subjects and controls (41
      [interquartile range, 30 to 511 v 38.5 [range, 32 to 47]; P = .58). There was no
      significant correlation between maternal and paternal Trait anxiety (P = .11).
      There was a significant reduction in State anxiety scores in both subject mothers
      (49.5 [interquartile range, 27 to 73) v38 [range, 31 to 49]; P = .01) and fathers
      (47 [interquartile range, 36 to 55] v 37 [interquartile range, 32 to 49]; P =
      .006) after pediatric surgical consultation. CONCLUSION: Counseling by specialist
      staff reduced levels of parental anxiety associated with the diagnosis of fetal
      surgical malformation.

PMID- 9766358
TI  - Correlation between Down's syndrome and malformations of pediatric surgical
      interest.
AB  - PURPOSE: This is a collaborative study carried out by Pediatric Surgeons of the
      "G.D'Annunzio" University and the Regional Association of Down Children of
      Abruzzo (Italy). METHODS: Data were collected of malformations combined with Down
      Syndrome (DS) during a 10-year period in a population of defined age to look for
      a possible improvement of the patients' life conditions. Reportedly, 50% of these
      patients may reach an age of about 60 years. RESULTS: One hundred twenty-seven DS
      subjects from this region were evaluated, 54% of whom had associated
      malformations (13% cardiac, 41% extracardiac, and 13% both). Seventeen patients
      of 53 underwent surgery for extracardiac malformations, with gastrointestinal
      malformations prevailing. The largest number of DS babies were born from mothers
      under 30 years of age; this is attributed to the largest birth rate and the least
      prevention at this age. Mothers older than 38 years gave birth to DS babies with
      the lowest rate of associated malformations. CONCLUSION: The role of the
      pediatric surgeon in multidisciplinary assistance for DS patients is stressed.

PMID- 9766359
TI  - Central venous catheter bloodstream infections in the neonatal intensive care
      unit.
AB  - PURPOSE: The goal of this study was to identify symptoms and signs related to
      central venous catheter (CVC) bloodstream infections (BSI) in neonatal intensive
      care unit (NICU) patients that would predict infection and to identify factors
      that might influence CVC longevity. METHODS: This was a retrospective cohort
      study evaluating 268 lines representing a total of 5,212 CVC days placed in 157
      NICU patients over 29 months by the pediatric surgery and neonatology services at
      one children's hospital. Centers for Disease Control (CDC) criteria were used to
      determine laboratory-confirmed BSI. Data were analyzed by univariate methods and
      logistic regression and determined significant at the P less than .05 level.
      RESULTS: Sixty-five lines (24%) from 54 patients had confirmed CVC BSI. Fever
      (49%) and pulmonary dysfunction (30%) were the most common symptoms of CVC BSI.
      Erythema or purulent discharge at the insertion site was found in only 20% of
      cases. Staphylococcus epidermidis was the most common organism isolated. Factors
      that significantly decreased the incidence of CVC BSI were increasing estimated
      gestational age (EGA; P < .0013) attime of insertion, associated vancomycin use
      at the time of catheter placement (P < .0057), and fewer days of catheter use (P
      < .0291). There were no significant differences noted caused by line location or
      catheter type. CONCLUSION: Fever and pulmonary dysfunction were the most common
      signs of CVC BSI in neonates. Lower EGA and increased catheter duration were
      significantly correlated with infection. The use of vancomycin concurrent with
      catheter insertion was associated with a decreased incidence of CVC BSI,
      howeverconcerns regarding the emergence of vancomycin-resistant organisms
      preclude support of its use as a prophylactic agent.

PMID- 9766361
TI  - Management of instrumental perforations of the esophagus occurring during
      treatment of corrosive strictures.
AB  - BACKGROUND: The initial symptoms of esophageal perforations (EP) may be subtle,
      but the progression is very rapid, and the outcome may be disastrous unless the
      diagnosis is made early and proper treatment is started immediately. METHODS:
      Between 1976 and 1996, 1,249 patients with caustic esophageal burns were treated
      at Ege University. The study group is composed of 52 patients with instrumental
      ER Perforations occured during dilatation attempts of esophageal strictures.
      Twelve patients were referred from other institutions after the occurrence of EP.
      RESULTS: In two patients, emergency surgical repair of the perforation was
      possible. Seventeen patients with unilateral and two patients with bilateral
      empyema were treated by pleural drainages. Anterior retrosternal mediastinal
      drainage was needed in one patient, and 11 patients required posterior
      mediastinal drainages. Three patients were treated by both anterior and posterior
      mediastinal drainage. Tracheoesophageal fistulas (TEF) developed in eight
      patients immediately after a dilatation attempt. Seven of these patients required
      esophageal replacement with colon to bypass the fistulas, and one patient in this
      group healed spontaneously. EP healed in 42.5 +/- 49.4 days. Twelve (23%)
      patients died of mediastinitis and sepsis. CONCLUSION: When EP is diagnosed and
      treated with these methods, the mortality rate should approach zero.

PMID- 9766360
TI  - Prehospital care and survival of pediatric patients with blunt trauma.
AB  - BACKGROUND: The aim of this study was to compare the outcome of severe blunt
      trauma in children receiving prehospital care from either physician-staffed
      advanced life support (ALS) units, or from basic life support (BLS) units staffed
      by emergency medical technicians. METHODS: The records of 288 children with
      severe blunt trauma who required intensive care in the regional level 1 trauma
      center or who died from their injuries were analyzed retrospectively. Patients
      were excluded if resuscitation at the scene was not attempted, if the level of
      prehospital care was unspecified, or if arrival at the level 1 trauma center was
      delayed beyond 150 minutes. Seventy-two patients met the inclusion criteria of
      BLS-, and 49 the criteria of ALS-prehospital care. RESULTS: A reduced mortality
      rate (22.4% v 31.9%) was seen in the ALS group, which was more apparent in a
      "salvageable but high-risk" subgroup, characterized by Glasgow Coma of Scale 4
      through 8, Pediatric Trauma Score of 0 through 5, and Injury Severity Score (ISS)
      of 25 through 49. However, a statistically significant difference was only seen
      when trauma severity was evaluated by the ISS. CONCLUSION: An improved outcome in
      children with severe blunt trauma has been demonstrated when prehospital care is
      provided by physician-staffed ALS units compared with BLS units.

PMID- 9766362
TI  - Early risk factors in pediatric renal transplantation at a single center.
AB  - BACKGROUND/PURPOSE: Renal transplantation is the preferred treatment for renal
      failure in childhood, but the incidence of graft failure is generally higher than
      that in adult recipients. A single center was studied to determine if there were
      any correctable factors that could contribute to graft failure. METHODS:
      Recipient, donor, and perioperative factors were analyzed using standard
      statistical tests in 59 pediatric renal transplants performed between 1992 and
      1995 using standard cyclosporin-based immunosuppression. RESULTS: Three factors
      were found to be significantly different between those recipients with good graft
      function and those who either died or were returned to dialysis. Any history of
      donor hypotension was a detrimental factor (P < .05, chi(2) test). In addition,
      those with failed grafts were more likely to have received their grafts from
      younger donors (P = .025, Mann Whitney U test). A third risk factor was a low
      postoperative central venous pressure in those whose graft ultimately failed (P =
      .0012, Mann Whitney U test). CONCLUSIONS: With a pediatric recipient who is
      stable and has a low priority for a renal graft, small donors, particularly those
      who have experienced hypotension, should be considered not suitable for
      transplantation. The chances of a successful graft can be improved by good
      communication between surgeon, pediatrician, and anesthetist. The importance of
      maintaining a positive central venous pressure is emphasised.

PMID- 9766363
TI  - Volvulus of the transverse colon in children.
AB  - Volvulus of the transverse colon is extremely rare in children. A case report of
      this unusual condition in a 9-year-old girl is presented together with a review
      of the literature. The transverse colon volvulus was managed operatively by
      detorsion. Four and half months later, she had a similar attack. Colonoscopic
      detorsion was performed with elective resection of the transverse colon and
      primary anastomosis. Recovery was uneventful. Possible factors of pathogenesis
      are discussed, and an outline of diagnostic and therapeutic measures are
      included.

PMID- 9766364
TI  - Double-barrelled colovaginoplasty in a patient with cloacal exstrophy variant.
AB  - Description of a new technique for combining colovaginoplasty with rectal pull
      through.

PMID- 9766365
TI  - In vivo karyotypic evolution with altered biological characteristics in a case of
      neuroblastoma.
AB  - Molecular and biological analyses of a neuroblastoma case in which the original
      tumor contained a nodular region are described. No significant difference was
      observed between the nodular and the surrounding tumor tissue with respect to
      histopathologic examination, N-myc amplification, and trkA expression. However,
      flow cytometric analysis demonstrated that the nodular region consisted of a
      hypertetraploid clone, whereas the surrounding tissue mostly contained a
      hyperdiploid clone. Chromosome analysis showed that each clone had a similar
      chromosome acquisition pattern, suggesting that the hypertetraploid cells of the
      nodular region arose from the hyperdiploid cells of the surrounding tissue.
      Moreover, primary culture findings of the tumor cells showed that the responses
      to nerve growth factor or retinoic acid were different between the two.
      Collectively, this case suggests the possibility that neuroblastoma acquires
      novel biological characteristics through karyotypic evolution in vivo.

PMID- 9766366
TI  - Surgery for thoracic empyema concurrent with rupture of lung abscesses in a
      child.
AB  - The authors report surgical treatment for thoracic empyema concurrent with
      rupture of lung abscesses and completely collapsed lung in a child. Right middle
      lobectomy for ruptured abscess, debridement and closure with interrupted sutures
      for another abscess in the lower lobe, and decortication were performed. Positive
      pressure ventilation was needed to prevent reexpansion pulmonary edema because of
      long-term collapsed lobes. The patient is doing well with no recurrent empyema or
      thoracic deformity at 3 years postoperation.

PMID- 9766367
TI  - Adenomyomatosis of the gallbladder in childhood.
AB  - Adenomyomatosis of the gallbladder (ADMG) is defined as an acquired disease
      characterized by localized or diffuse hyperplastic extensions of the mucosa into,
      and often beyond, the thickened gallbladder muscular layer (Rokitansky-Aschoff's
      sinuses). In recent years, attention has been drawn to its malignant potential.
      The occurrence of ADMG has never been reported in children. The authors report
      the case of a 5-year-old boy with symptomatic ADMG, who was successfully treated
      by laparoscopic cholecystectomy.

PMID- 9766368
TI  - Congenital lateral cervical cysts of infancy.
AB  - The etiology of lateral cervical cysts in infancy is complex. The cysts are
      congenital in origin and are derived from the third or fourth branchial
      apparatus. The authors describe two cases of congenital lateral cervical cysts
      with an internal opening in the pyriform sinus and possible origin in the third
      branchial arch. The embryology, clinical presentation, and operative management
      of this condition is reviewed.

PMID- 9766369
TI  - Primary pneumococcal peritonitis complicated by exudative pleural effusion in an
      adolescent girl.
AB  - A healthy, young adolescent girl developed primary pneumococcal peritonitis, an
      infection rarely reported in this age group in North America. Her course was
      further complicated by exudative pleural effusion and pneumonia despite receiving
      10 days of clindamycin therapy. Laparascopy proved useful in making the initial
      diagnosis, but may have contributed to the pathogenesis of the pulmonary process.
      Case presentation, management, and etiology are discussed.

PMID- 9766370
TI  - Juvenile polyp in esophageal colon interposition.
AB  - Esophageal polyps are rare in children, whereas colorectal juvenile polyps are
      common. An 11-year-old boy with an esophageal colonic interposition for an
      esophageal stricture secondary to caustic injury was found to have a polypoid
      mass in the interposed colon. Fiberoptic endoscopic removal with diathermy was
      performed. Histological examination confirmed it was a juvenile polyp. The
      occurrence of a polyp in a colon removed from its natural location and serving a
      different function suggests the possibility that an unknown factor produced by
      colonic cells play a pivotal role in its development.

PMID- 9766371
TI  - Colon perforation in hyperimmunoglobulin E syndrome.
AB  - Colon perforation from hyperimmunoglobulin E syndrome is very rare, and only one
      case has been reported in the English-language literature. Herein, the authors
      report another case of colon perforation experienced in hyperimmunoglobulin E
      syndrome. The patient was an 8-year-old girl with frequent infection, eczematoid
      dermatitis, and an increased serum level of immunoglobulin E. During admission,
      panperitonitis developed caused by colon perforation. Treatment was resection of
      the perforated segment of the colon and a double-barrel colostomy. The patient
      has been doing well 18 months after treatment.

PMID- 9766372
TI  - Atresia of the appendix.
AB  - A 4-day-old black male underwent laparotomy for intestinal obstruction. At
      surgery, multiple jejunal atresias (type IV) of the jejunum were detected. As an
      incidental finding, atresia of the appendix was also present. The jejunal atresia
      was repaired, and resection of the tip of the cecal pole and atretic appendix was
      performed. Gross and histological examination confirmed the presence of a type IV
      atresia of the jejunum and a cordlike (type II) atresia of the appendix with
      inflammatory changes in the tip of the appendix. The boy made an uneventful
      recovery. Examination of all organ systems did not show any associated findings,
      and the family history was unremarkable. To our best knowledge, this case
      represents the first case of atresia of the appendix described in the literature.

PMID- 9766373
TI  - Undescended testicle associated with spigelian hernia.
AB  - The authors encountered a patient with a spigelian hernia (SH) and undescended
      testicle (UDT), making the fourth reported case with this combination. This
      patient provides further evidence that congenital SH predisposes neonates to UDT.

PMID- 9766374
TI  - Spontaneous regression of tumoral calcinosis in an infant: a case report.
AB  - A case of tumoral calcinosis presenting as a supraclavicular mass in an infant is
      reported. After confirmation by incisional biopsy, the lesion spontaneously
      resolved without further surgical or medical treatment. This phenomenon has not
      been described previously in a child with this condition.

PMID- 9766375
TI  - Fetus-in-fetu: a case report and review of the literature.
AB  - A unique case of intraperitoneal fetus-in-fetu attached to an ovary is presented.
      An asymptomatic newborn girl was found to have a mobile cystic mass in right side
      of her abdomen. Radiological investigations showed fetus-in-fetu. During
      laparotomy, an intraperitoneal fetus-in-fetu was found attached to right ovary
      and vascular pedicle to ovarian vessels. Only 79 cases of fetus-in-fetu have been
      reported, and this is the first such case attached to an ovary.

PMID- 9766376
TI  - Acute scrotum: an exceptional presentation of acute nonperforated appendicitis in
      childhood.
AB  - Acute scrotum is an exceptional form of presentation of acute appendicitis in the
      pediatric age group. Only 14 cases have been described in literature. The authors
      report a case of an 8-year-old boy with a 12-hour history of right hemiscrotal
      pain secondary to acute retrocecal nonperforated appendicitis. Surgical
      exploration showed a patent "processus vaginalis."

PMID- 9766377
TI  - Adenocarcinoma of the appendix in a child.
AB  - Adenocarcinoma of the appendix is unusual at any age but occurs mostly in an
      elderly population. The authors report a unique case presenting in a 10-year-old
      child and emphasize the importance of subjecting all resected specimens to
      histological examination.

PMID- 9766378
TI  - Laparoscopic splenic cystectomy: a case report.
AB  - Congenital epidermoid splenic cysts are very rare. They are known to become
      symptomatic as a consequence of enlargement, hemorrhage, rupture, or infection.
      Recent options in the treatment of splenic cysts have included percutaneous
      drainage, partial splenectomy, or open splenic cystectomy. The authors present
      the first report of a pediatric patient with a large epidermoid cyst of the
      spleen treated by laparoscopic partial cyst excision and omental packing. Follow
      up at 1 year confirms no recurrence. Laparoscopy provides a minimal access method
      of obtaining pathological confirmation of diagnosis, reduction of cyst
      complications, and a short hospital stay, while preserving splenic function.

PMID- 9766379
TI  - Allantoic cyst and persistent urachal-allantoic communication: a rare umbilical
      anomaly.
AB  - True cysts of the umbilical cord are distinctly rare. A cyst lined by
      uroepithelium is described in a newborn in whom the cyst communicated freely with
      a patent urachal system. It is assumed that this most likely represents a remnant
      cyst of the allantois--an anomaly not described previously.

PMID- 9766380
TI  - An unusual case of esophageal atresia and double distal tracheoesophageal
      fistula.
AB  - This report describes a neonate with a very rare and an unusual variety of
      esophageal atresia and tracheoesophageal fistula. The anomaly consisted of
      esophageal atresia and double distal tracheoesophageal fistula. The two fistulae
      as well as part of the distal esophagus were made up of tracheobronchial tissues.
      The embryology of the anomaly is also discussed.

PMID- 9766381
TI  - Venovenous extracorporeal membrane oxygenation in newborn infants using the
      umbilical vein as a reinfusion route.
AB  - PURPOSE: The authors report on four neonates treated with venovenous (VV)
      extracorporeal membrane oxygenation (ECMO) using the umbilical vein as a
      reinfusion route. METHODS: From 1994 to 1997, 26 instances VV-ECMO in neonates
      have been carried out at our neonatal center for the treatment of severe
      respiratory and cardiac failure. Among them, 22 patients could be treated with VV
      ECMO mainly using 15F double-lumen catheter (DLC), adding the cephalic drainage
      using another catheter. In the remaining four cases, however, attempts to insert
      the DLC into the right internal jugular vein failed because the vein was too
      small or technical problems. For such instances, two catheters were cannulated
      into the right atrium and the cephalic portion of the right internal jugular
      vein, respectively. These two venous catheters were connected to the drainage
      route of ECMO circuit with a "Y" connector. Then, the umbilical vein was
      cannulated with 10F or 8F catheter, which was connected to the reinfusion route
      of ECMO to return the oxygenated blood to the infant. RESULTS: The median age at
      which ECMO was initiated was 18 hours, and the median ECMO course was 72 hours.
      The liver function tests were slightly and transiently worsened in two patients
      during VV perfusion, (in one patient serum glutamic-oxaloacetic transaminase
      [SGOT] elevated to 76 IU/L and serum glutamic-pyruvic transaminase [SGPT] to 49
      IU/L, and in another patient SGOT elevated to 56 IU/L and SGPT remained in normal
      range). Preumbilical cannula pressures were measured in two patients. In a
      patient who used 10F umbilical cannula, the preumbilical maximum pressure was 43
      mm Hg at 250 mL/min of ECMO flow. In another with an 8F catheter, it was 72 mm Hg
      at 180 mL/min of ECMO flow. All of the patients survived without any neurological
      complications. CONCLUSIONS: If the right internal jugular vein would not
      accommodate the DLC, VV-ECMO using the umbilical vein as a infusion route could
      be selected.

PMID- 9766382
TI  - Two cases of torsion of the gallbladder diagnosed preoperatively.

PMID- 9766383
TI  - Balloon extraction of esophageal foreign bodies in children.

PMID- 9766384
TI  - Morphological substrates underlying opioid, epinephrine and gamma-aminobutyric
      acid inhibitory actions in the rat locus coeruleus.
AB  - The locus coeruleus (LC) has been implicated in attentional processes related to
      orienting behaviors, learning and memory, anxiety, stress, the sleep-wake cycle,
      and autonomic control, as well as to contributing to the affective state. Direct
      activation of LC neurons causes desynchronization of the electroencephalogram,
      suggesting that the LC is an important modulator of the behavioral state. The LC
      has been an intensely studied neuronal system, as the physiology and pharmacology
      of this nucleus is well understood. This is mainly because of the similarity in
      neurochemical composition of LC cells which all contain norepinephrine in the
      rat. However, the homogeneity in neurotransmitter content in LC neurons is
      sharply contrasted by the heterogeneity of neurochemicals found in its afferent
      processes. Among these are axon terminals that contain inhibitory and excitatory
      amino acids, monoamines, and neuropeptides, many of which have been shown to
      exert differential physiological effects on LC discharge activity. Although much
      attention has focused on physiological activation of LC neurons, substantial
      evidence indicates that diverse afferents prominently inhibit noradrenergic
      cellular activity. Such inhibitory neurochemicals, which arise from local and
      extrinsic sources, include gamma-aminobutyric acid (GABA) and epinephrine as well
      as the neuropeptides methionine5-enkephalin and leucine5-enkephalin. Inhibitory
      transmission in the LC has widespread implications for norepinephrine release at
      diverse postsynaptic targets, and clinically useful pharmacological agents such
      as clonidine, an alpha2 adrenergic receptor agonist that potently inhibits the
      firing of LC neurons, alleviate some negative physical symptoms observed
      following withdrawal from opiates. In the present review, the synaptic and
      functional organization of selected inhibitory-type neurotransmitters in the LC
      obtained from immunoelectron microscopic data will be discussed.

PMID- 9766385
TI  - Angiotensin receptors in the nervous system.
AB  - In addition to its traditional role as a circulating hormone, angiotensin is also
      involved in local functions through the activity of tissue renin-angiotensin
      systems that occur in many organs, including the brain. In the brain, both
      systemic and presumptive neurally derived angiotensin and angiotensin metabolites
      act through specific receptors to modulate many functions. This review examines
      the distribution of these specific angiotensin receptors and discusses evidence
      regarding the function of angiotensin peptides in various brain regions.
      Angiotensin AT1 and AT2 receptors occur in characteristic distributions that are
      highly correlated with the distribution of angiotensin-like immunoreactivity in
      nerve terminals. Acting through the AT1 receptor in the brain, angiotensin has
      effects on fluid and electrolyte homeostasis, neuroendocrine systems, autonomic
      pathways regulating cardiovascular function and behavior. Angiotensin AT1
      receptors are also found in many afferent and efferent components of the
      peripheral autonomic nervous system. The role of the AT2 receptor in the brain is
      less well understood, although recent knockout studies point to an involvement
      with behavioral and cardiovascular functions. In addition to the AT1 and AT2
      receptors, receptors for other fragments of angiotensin have been proposed. The
      AT4 binding site, which binds angiotensin, has a widespread distribution in the
      brain quite distinct from that of the AT1 and AT2 receptors. It is associated
      with many cholinergic neuronal groups and also several sensory nuclei, but its
      function remains to be determined. Our discovery that another brain-derived
      peptide binds to the AT4 binding site in the brain and may represent the native
      ligand is discussed. Overall, the distribution of angiotensin receptors in the
      brain indicate that they play diverse and important physiological roles in the
      nervous system.

PMID- 9766386
TI  - Specificity of interleukin-1beta-induced changes in monoamine concentrations in
      hypothalamic nuclei: blockade by interleukin-1 receptor antagonist.
AB  - The purpose of this study was to examine specificity in the effects of
      interleukin-1beta (IL-1beta) on monoamines in various areas of the hypothalamus.
      Adult male rats were injected i.p. with saline or 2.5 or 5.0 microg of IL-1beta
      or were pretreated with 500 microg of IL-1 receptor antagonist (IL-1ra) followed
      5 min later by 5 microg of IL-1beta. The paraventricular nucleus (PVN), arcuate
      nucleus (AN), median eminence (ME), and medial preoptic area (MPA) were
      microdissected and analyzed for neurotransmitter concentrations by high
      performance liquid chromatography with electrochemical detection (HPLC-EC). In
      the PVN, IL treatment produced significant increases in the concentrations of
      norepinephrine (NE), dopamine (DA), DA metabolite dihydroxyphenylacetic acid
      (DOPAC), serotonin (5-HT), and its metabolite 5-hydroxyindoleacetic acid (5
      HIAA). IL-1 treatment increased the concentrations of NE and DA in the AN but
      only of NE in the ME, and it was without any effect in the MPA. Pretreatment with
      IL-1ra completely blocked the IL-1 effects. It is concluded that IL-1 induces
      highly specific changes in monoamine metabolism in the hypothalamus, and the
      nature of these changes depends on specific hypothalamic nuclei.

PMID- 9766387
TI  - Truncated green fluorescent protein mutants and their expression in Aplysia
      neurons.
AB  - We determined in detail the primary structure requirements for green fluorescence
      of the jellyfish green fluorescent protein (GFP) and of its improved mutants
      (S65T and 1167T). We performed a deletion mapping in combination with
      fluorescence-activated cell sorting (FACS) and spectrofluorometry. This showed
      that deletion of up to nine amino acids at the C-terminal end of GFP had no
      deleterious effect on the fluorescent activity of GFP; in fact the deletion
      increased intensity of fluorescence. Further truncation of up to 11 amino acids
      resulted in partial impairment in maximal fluorescence. The GFP fluorescence was
      completely disrupted when more than 12 amino acids were deleted out of the C
      terminal. Truncated mutants or their fusion genes with lacZ emitted fluorescence
      when plasmids encoding them were introduced by microinjection into Aplysia
      neurons.

PMID- 9766389
TI  - Suppressive effect of vagal afferents on the activity of the trigeminal spinal
      neurons related to the jaw-opening reflex in rats: involvement of the endogenous
      opioid system.
AB  - The purpose of the present study is to test the hypothesis that via the
      endogenous pain control system, vagal afferent input modulates the activity of
      the trigeminal spinal nucleus oralis (TSNO) related to the tooth pulp (TP)-evoked
      jaw-opening reflex (JOR). Extracellular single-unit recordings were made from 36
      TSNO units responding to TP electrical stimulation with a constant temporal
      relationship to a digastric electromyogram (dEMG) signal in 26 pentobarbital
      anesthetized rats. The activity of 36 TSNO neurons and the amplitude of the dEMG
      increased proportionally during 1.0-3.5 times the threshold for JOR. Some of
      these neurons (4 out of 5) were also excited by chemical stimulation (bradykinin,
      1-2 microl, 1 mM) of TP. In 31 out of 36 TSNO neurons (86%), their activities
      during tooth pulp stimulation were suppressed by conditioning stimulation of the
      right vagus nerve. The suppressive effect of vagal afferent stimulation occurred
      at conditioning-test intervals of 20-150 ms after the onset of the stimulation,
      and its maximal suppressive effect occurred at approximately 50 ms. The mean time
      course of this suppressive effect paralleled that of the dEMG. After
      administration of naloxone (0.5 and 1.0 mg/kg, i.v.), an opiate receptor blocker,
      the suppressive effect on the activity of TSNO neurons (6 out of 8) was
      significantly attenuated at the conditioning-test interval of 50 ms compared to
      the control (p < 0.01). These results suggested that vagal afferent input
      inhibits nociceptive transmission in the TSNO related to TP-evoked JOR and this
      inhibitory effect may occur via the endogenous opioid system in rats.

PMID- 9766388
TI  - Propriospinal neurons in the C1-C2 spinal segments project to the L5-S1 segments
      of the rat spinal cord.
AB  - Physiological studies indicate that neurons in the upper cervical spinal cord
      have descending projections to the lumbosacral spinal cord and mediate inhibition
      of dorsal horn neurons activated from afferent input. In the present study,
      retrograde tracing techniques were used to examine the distribution of
      propriospinal neurons in C1-C2 spinal segments that project to lumbosacral spinal
      segments. Fluorogold or horseradish peroxidase were injected unilaterally or
      bilaterally into the L5-S1 spinal segments. After 2-4 days, rats were perfused
      with fixative and C1-C2 spinal segments were processed for retrograde labeling.
      Numerous neurons were found in the C1-C2 segments. In unilaterally and
      bilaterally injected rats, retrogradely labeled neurons were located on both the
      ipsilateral and contralateral sides. Retrogradely labeled neurons were located in
      the following locations: lateral cervical and spinal nuclei, nucleus proprius,
      ventral horn and the central gray region (area X). These studies demonstrate a
      descending projection from C1-C2 segments to the lower lumbar and sacral spinal
      cord. We hypothesize that many of these C1-C2 propriospinal neurons are important
      in modulating responses of spinal neurons at lower segmental levels to various
      peripheral stimuli.

PMID- 9766390
TI  - Behavioural and hormonal effects of restraint stress and formalin test in male
      and female rats.
AB  - The formalin test was used to measure the analgesia induced by restraint in male
      and female rats. Animals were restrained for 30 min or left undisturbed in their
      cage and then (1) killed immediately to collect blood for hormonal
      determinations; or (2) subcutaneously injected with formalin in the hind paw (or
      sham-injected), introduced to an open field for recording of behaviour, and
      killed at the end of this procedure. In both experiments, corticosterone was
      found to be higher in females. In Experiment 1, the ability of restraint to be
      stressful was confirmed by the increase in corticosterone in both sexes and by
      the decrease of testosterone in males. In Experiment 2, restraint-treatment
      induced a reduction in licking and flexing that was limited to the second phase.
      The reduction occurred in different periods and to a different degree in the two
      sexes; it was greater in females. Spontaneous behaviours showed sex differences
      in restraint-treated but not in formalin-treated animals. The results show that
      the hormonal effects observed after restraint are not present after the formalin
      test and that the marked analgesia observed with phasic painful stimuli does not
      occur with a longer-lasting one such as that induced by formalin, after which
      only partial and short-lasting effects were observed.

PMID- 9766391
TI  - Impaired arterial baroreflex regulation of heart rate after blockade of P2
      purinoceptors in the nucleus tractus solitarius.
AB  - Activation of P2x-purinoceptors in the nucleus tractus solitarius (NTS) via
      microinjection of ATP mimics baroreflex responses (bradycardia, hypotension);
      however, the physiological role of these receptors in cardiovascular control
      remains unclear. We tested whether blockade of these receptors attenuates
      arterial baroreflex control of heart rate (HR). Baroreflex-induced changes in HR
      (via graded i.v. infusion of phenylephrine and nitroprusside) were observed in
      seven alpha-chloralose/urethane anesthetized male Sprague-Dawley rats before and
      after microinjection of the purinergic P2 receptor antagonist suramin (0.5 nmol
      in 50 nL) into the subpostremal NTS. Before suramin, typical baroreflex changes
      in HR were observed (maximum gain, Gmax = 2.94 +/- 0.54 bpm/mmHg). Suramin
      markedly impaired baroreflex-induced changes in HR (gain = 0.02 +/- 0.08 and 0.18
      +/- 0.09 bpm/mmHg for increases and decreases in mean arterial blood pressure,
      respectively); however, after 90-130 min, HR and baroreflex reactivity returned
      to control levels. Microinjections of vehicle into the same area did not alter
      baroreflex function. In addition, suramin did not alter the depressor responses
      to microinjections of glutamate into the same site of the NTS. We conclude that
      normal P2x-purinoceptor function in subpostremal NTS may be necessary for
      baroreflex regulation of HR.

PMID- 9766392
TI  - Effects of brain testosterone implants on appetitive and consummatory components
      of male sexual behavior in Japanese quail.
AB  - Aromatization of testosterone (T) into an estrogen is necessary for the
      activation of consummatory and appetitive sexual behavior in male Japanese quail.
      T action within the medial preoptic nucleus (POM) is necessary and sufficient to
      activate consummatory behavior, and some evidence suggests that POM might be
      involved in the control of appetitive behavior, but other brain regions, such as
      the bed nucleus of the stria terminalis (BST), an area that contains a dense
      population of aromatase-immunoreactive neurons, are also likely to be involved.
      This study was performed to assess the effects of stereotaxic T implants
      targeting either the POM or the BST on the activation of both components of
      sexual behavior in castrated male quail. Appetitive sexual behavior was measured
      by an acquired social proximity response in which a male will approach a window
      providing visual access to a female after the window has been repeatedly paired
      with physical access to a female and the possibility to freely interact with her.
      Rhythmic cloacal sphincter movements that are produced by the male when given
      visual access to a female were used as another measure of appetitive sexual
      behavior that does not appear to depend on sexual learning. The experiments
      confirmed that copulation is necessary for males to develop the social proximity
      response that is used to measure the appetitive sexual behavior. T implants in
      the POM activated both components of sexual behavior, suggesting that these
      components cannot be completely dissociated. In contrast, T implants located
      within the BST did not affect either component, but because implants in the BST
      did not activate copulatory behavior, these results do not preclude a role for
      BST in the expression of a previously acquired appetitive sexual behavior.

PMID- 9766393
TI  - Role of opioidergic and monoaminergic neurotransmission in the GnRH release
      mechanism of EBP-primed OVX rats.
AB  - We examined the effect of intracerebroventricular (i.c.v.) administration of mu
      opioid agonist, morphine, and its antagonist naloxone followed by morphine on the
      activities of monoamine-metabolizing enzymes, namely tyrosine hydroxylase (TH)
      and monoamine oxidase (MAO) along with adenosinetriphosphatase (Na+, K+ -ATPase),
      the enzyme responsible for the maintenance of ionic gradients across the
      membrane, in seven discrete regions of brain from estrogen- and progesterone
      primed ovariectomized rats. TH activity decreased after morphine treatment in
      some areas such as the median eminence-arcuate region (ME-ARC), the amygdala, and
      the thalamus, showing statistically significant change. MAO activity increased in
      all the areas studied, but more appreciable change was observed in medial
      preoptic area (mPOA), the ME-ARC region, and the cortex. Pronounced increase in
      Na+, K+ -ATPase enzyme activity was observed after the drug treatment. Naloxone
      given prior to morphine injection resulted in recovery of the enzyme activities
      in most of the areas studied. Our study may provide insights into the precise
      opioidergic modulation of gonadotropin releasing hormone (GnRH) release
      mechanisms through the involvement of monoaminergic system, elucidating the basis
      of various neuronal dysfunctions and their management in opioid addicts.

PMID- 9766394
TI  - Tyrosine phosphorylation is increased in the rat hippocampus during the status
      epilepticus induced by pilocarpine.
AB  - Phosphorylation of tyrosine residue in proteins is an important modulatory
      process for membrane transduction and cell signaling and for several cellular
      functions. The concentration and distribution of phosphotyrosine proteins were
      analyzed in the hippocampi of rats in the model of epilepsy induced by
      pilocarpine using Western blotting and immunohistochemistry. The concentration of
      several phosphotyrosine proteins increased during status epilepticus. During the
      seizure-free period and the chronic period of this epilepsy model, the hippocampi
      of rats did not exhibit changes in the expression of these proteins.
      Immunohistochemistry showed an increased immunoreactivity throughout the
      hippocampal formation of rats 1 h after status epilepticus that was acutely
      induced by pilocarpine. Animals killed after 3 h of status epilepticus showed an
      increased expression of phosphotyrosine in the hippocampal hilus and CA3 regions.
      After 5 h of status epilepticus, phosphotyrosine immunoreactivity persisted only
      in the CA3 region. After 12 h of status epilepticus, the hippocampal formation
      exhibited a normal phosphotyrosine immunostaining, showing that the increased
      expression of these proteins is related to the acute phase and that several
      intracellular events could undergo modifications during the status epilepticus
      induced by pilocarpine.

PMID- 9766395
TI  - Long-lasting structural changes in CA3 hippocampal and layer V motor cortical
      pyramidal neurons associated with self-stimulation rewarding experience: a
      quantitative Golgi study.
AB  - Self-stimulation (SS) rewarding experience induced structural changes in CA3
      hippocampal and layer V motor cortical pyramidal neurons in adult male Wistar
      rats has been demonstrated. In the present study, whether these structural
      changes are transient or of a permanent nature was evaluated. Self-stimulation
      experience was provided for 1 h daily over a period of 10 days through
      bilaterally implanted bipolar electrodes in the lateral hypothalamus and the
      substantia nigra-ventral tegmental area. Following 10 days of SS experience, the
      rats were sacrificed after an interval of 30 and 60 days for the quantitative
      analysis of the dendritic morphology in Golgi stained CA3 hippocampal and layer V
      motor cortical pyramidal neurons. The results revealed a significant increase in
      the dendritic branching points and intersections in apical and basal dendrites in
      both types of neurons in 30 days post-SS group compared to sham control. The
      total number of apical and basal dendrites were significantly increased in both
      30 and 60 days post-SS groups of rats. This study suggests that SS experience
      induced structural changes are sustainable, even in the absence of rewarding
      experience.

PMID- 9766396
TI  - Zinc transport from the striatum and substantia nigra.
AB  - 65Zn was unilaterally injected into the striatum or substantia nigra of rats to
      see the transport of intracerebral zinc (Zn). In the case of intrastriatal
      injection, 65Zn was densely distributed in the ipsilateral medial forebrain
      bundle (MFB) and the substantia nigra. On unilateral colchicine injection into
      the MFB, 65Zn distribution in the ipsilateral substantia nigra decreased
      significantly compared to that of the contralateral one after 65Zn injection into
      the bilateral striata. These results suggest the presence of axonal transport of
      65Zn taken up by striatonigral gamma-aminobutyric acid (GABA)-ergic and/or
      nigrostriatal dopaminergic neurons. On the other hand, in the case of intranigral
      injection, 65Zn was distributed in the ipsilateral MFB, striatum, globus
      pallidus, pontine reticular nuclei, and pontine nuclei. 65Zn distribution in the
      pons 1 day after intranigral injection was very similar to that 6 days after
      intrastriatal injection, suggesting that, in the case of intrastriatal injection
      of 65Zn, nigral 65Zn, which was transported anterogradely and/or retrogradely
      from the striatum, was transported to the postsynaptic neurons through the
      synapse and then transported to the pons.

PMID- 9766397
TI  - Auditory cortical projections to the cat inferior colliculus.
AB  - The projection from 11 auditory cortical areas onto the subdivisions of the
      inferior colliculus was studied in adult cats by using two different anterograde
      tracers to label cortico-collicular (CC) axon terminals. The main results were
      that: 1) a significant CC projection arose from every field; 2) the principal
      inferior collicular targets were the dorsal cortex, lateral nucleus, caudal
      cortex, and intercollicular tegmentum, with only a sparse projection to the
      central nucleus; 3) the input was usually bilateral, with the ipsilateral side by
      far the most heavily labeled, and the contralateral projection was a symmetrical
      subset of the ipsilateral input; 4) the CC system is both divergent and
      convergent, with single cortical areas projecting to six or more collicular
      subdivisions, and each auditory midbrain subdivision receiving a convergent
      projection from two to ten cortical areas; 5) cortical areas devoid of tonotopic
      organization have topographic projections to collicular target nuclei; 6) the
      heaviest CC projection terminated in the caudal half of the inferior colliculus;
      and finally, 7) the relative strength of the cortico-collicular labeling was far
      less than that of the corresponding corticothalamic projection in the same
      experiments. The CC system is strategically placed to influence both descending
      and ascending pathways arising in the inferior colliculus. Nuclei that
      participate in the premotor system, like the inferior collicular subdivisions
      that project to the pons, receive substantial corticofugal input. Both the dorsal
      (pericentral) and the lateral (external) nuclei of the inferior colliculus
      project to parts of the medial geniculate body whose closest auditory
      affiliations are with non-tonotopic cortical regions involved in higher order
      auditory perception. The cortico-collicular system may link brainstem and
      colliculo-thalamic circuits to coordinate premotor and perceptual aspects of
      hearing.

PMID- 9766398
TI  - Temporal and spatial patterns of c-fos mRNA induced by intravenous interleukin-1:
      a cascade of non-neuronal cellular activation at the blood-brain barrier.
AB  - Brain cells responsive to a peripheral immune challenge, identified by in situ
      hybridization of c-fos mRNA following intravenous administration of the
      proinflammatory cytokine interleukin-1beta (IL-1) or sterile saline, were
      investigated at 0.5, 1, and 3 hours postinjection in rats. Doses of IL-1 ranged
      from 0.05 to 10 microg/kg; induction of c-fos mRNA occurred at > or = 0.5 pg/kg.
      The majority of IL-1-induced c-fos mRNA-positive cells were non-neuronal cells
      located in barrier regions of the brain. The cells became radiolabeled in two
      separate but related spatiotemporal patterns. The first pattern, occurring at 0.5
      hour, was characterized by c-fos mRNA labeling of cells of the outer meninges
      (mainly arachnoid), blood vessels (arteries, veins, and capillaries), and choroid
      plexus. This activation pattern disappeared at 1 hour. At 3 hours, a second
      activation pattern appeared in cells located just inside the now quiescent
      barrier cells. In addition, the circumventricular organs each showed
      characteristic spatiotemporal labeling patterns resulting from successive
      activation of specific cell types, with a general spread of activation directed
      away from the circumventricular organs over time. At 3 hours post IL-1, c-fos and
      glial fibrillary acidic protein (GFAP) mRNAs showed colocalization in the arcuate
      nucleus/median eminence/glia limitans region. We propose that the first wave of
      activation is elicited by blood-borne immune signals, but the second wave is
      caused by molecules generated within the first set of activated cells. The
      transduced signal appears to propagate to neighboring receptive cells by
      extracellular diffusion. In this manner, blood-brain barrier cells can transduce
      peripheral IL-1 signals in widespread areas of the brain, although the
      circumventricular organs may be the most effective loci for signal transduction.

PMID- 9766399
TI  - Timing and origin of the first cortical axons to project through the corpus
      callosum and the subsequent emergence of callosal projection cells in mouse.
AB  - A precise knowledge of the timing and origin of the first cortical axons to
      project through the corpus callosum (CC) and of the subsequent emergence of
      callosal projection cells is essential for understanding the early ontogeny of
      this commissure. By using a series of mouse embryos and fetuses of the hybrid
      cross B6D2F2/J weighing from 0.36 g to 1.0 g (embryonic day E15.75-E17.25), we
      examined the spatial and temporal distribution of callosal projection cells by
      inserting crystals of the lipophilic dye (DiI: 1,1'-dioctadecyl-3,3,3',3'
      tetramethylindocarbocyanine perchlorate) into the contralateral white matter just
      lateral to the midsagittal plane. Around 0.4 g or E15.8, retrogradely labeled
      cells were found restricted to a discrete cluster continuously distributed from
      the most ventral part of presumptive cingulate cortex to the hippocampus. During
      subsequent development, however, the tangential distribution of these labeled
      cells in ventromedial cortex did not extend further dorsally, and in fetuses
      where the CC became distinct from the hippocampal commissure (HC), labeled axons
      of cells in the ventral cingulate cortex were observed to intersect the callosal
      pathway and merge with labeled axons of the HC derived from cells in the
      hippocampus. The first cortical axons through the CC crossed the midline at about
      0.64 g or E16.4, and these axons originated from a scattered neuronal population
      in the dorsal to lateral part of the presumptive frontal cortex. The earliest
      callosal cells were consistently located in the cortical plate and showed an
      immature bipolar appearance, displaying an ovoid- or pearl-shaped perikaryon with
      an apical dendrite coursing in a zig-zagging manner toward the pial surface and a
      slender axon directed toward the underlying white matter. Callosal projection
      cells spread progressively with development across the tangential extent of the
      cerebral cortex in both lateral-to-medial and rostral-to-caudal directions. In
      any cortical region, the first labeled cells appeared in the cortical plate and
      their number in the subplate was insignificant compared to that in the cortical
      plate. Thus, these results clarify that the CC is pioneered by frontal cortical
      plate cells, and the subsequent ontogeny of callosal projection cells proceeds
      according to the gradient of cortical maturation.

PMID- 9766400
TI  - Noradrenergic system of the zebra finch brain: immunocytochemical study of
      dopamine-beta-hydroxylase.
AB  - Oscine birds are among the few animal groups that have vocal learning, and their
      brains contain a specialized system for song learning and production. We describe
      here the immunocytochemical distribution of dopamine-beta-hydroxylase (DBH), a
      noradrenergic marker, in the brain of an oscine, the zebra finch (Taeniopygia
      guttata). DBH-positive cells were seen in the locus coeruleus, the nucleus
      subcoeruleus ventralis, the nucleus of the solitary tract, and the caudolateral
      medulla. Immunoreactive fibers and varicosities had a much wider brain
      distribution. They were particularly abundant in the hippocampus, septum,
      hypothalamus, area ventralis of Tsai, and substantia nigra, where they formed
      dense pericellular arrangements. Significant immunoreactivity was observed in
      auditory nuclei, including the nucleus mesencephalicus lateralis pars dorsalis,
      the thalamic nucleus ovoidalis, field L, the shelf of the high vocal center
      (HVC), and the cup of the nucleus robustus archistriatalis (RA), as well as in
      song control nuclei, including the HVC, RA, the lateral magnocellular nucleus of
      the anterior neostriatum, and the dorsomedial nucleus (DM) of the intercollicular
      complex. Except for the DM, DBH immunoreactivity within song nuclei was
      comparable to that of surrounding tissues. Conspicuously negative were the lobus
      paraolfactorius, including song nucleus area X, and the paleostriatum. Our
      results are in agreement with previous studies of the noradrenergic system
      performed in nonoscines. More importantly, they provide direct evidence for a
      noradrenergic innervation of auditory and song control nuclei involved in song
      perception and production, supporting the notion that noradrenaline is involved
      in vocal communication and learning in oscines.

PMID- 9766401
TI  - GABA, GABA transporters, GABA(A) receptor subunits, and GAD mRNAs in the rat
      parabrachial and Kolliker-Fuse nuclei.
AB  - In the present study, we investigated the key molecules that determine gamma
      aminobutyric acid (GABA)ergic signal transduction in the parabrachial/Kolliker
      Fuse complex (PB/KF) by means of immunocytochemistry and in situ hybridization.
      Our data demonstrate a dense plexus of GABA-immunoreactive (-ir) varicosities
      throughout the nuclei of the PB and the KF. The number of neurons expressing
      GAD65 or GAD67 mRNA was fairly low in the PB, whereas caudally in the KF an
      accumulation of GAD-expressing neurons was observed. The GABA transporter-3 (GAT
      3) was detected in all parts of the PB/KF, whereas immunolabeling for GAT1 was
      not observed. All nuclei of the PB and the KF exhibited immunoreactivity for the
      gamma2-, alpha2-, and alpha3-subunits of the GABA(A) receptor. Gamma2-ir was
      strong and similar in all PB/KF nuclei. In contrast, alpha2-labeling was
      particularly intense in the superior lateral PB, and alpha3-labeling was most
      prominent in the external lateral and external medial PB, compared with the
      remaining nuclei. With respect to the subcellular localization, we found gamma2
      ir in cell bodies and higher order dendrites, whereas alpha2- and alpha3-ir was
      predominantly found in cell bodies. Immunolabeling for the beta2/3- and the
      alpha1-subunit was seen in cell bodies and presumed dendritic profiles. The
      staining intensity was strongest in the dorsal lateral PB. Most importantly, the
      external lateral PB and the waist area were totally devoid of beta2/3- and alpha1
      ir. Our data suggest that neural processing in the PB/KF is under a strong
      GABAergic inhibition that is apparently mediated by different types of GABA(A)
      receptors in functionally different pathways through the PB/KF.

PMID- 9766402
TI  - Differential regulation of ciliary neurotrophic factor receptor-alpha expression
      in all major neuronal cell classes during development of the chick retina.
AB  - Ciliary neurotrophic factor (CNTF) exerts a multiplicity of effects on a broad
      spectrum of target cells, including retinal neurons. To investigate how this
      functional complexity relates to the regulation of CNTF receptor alpha (CNTFR
      alpha) expression, we have studied the developmental expression of the receptor
      protein in chick retina by using immunocytochemistry. During the course of
      development, the receptor is expressed in all retinal layers, but three levels of
      specificity can be observed. First, the expression is regulated temporally with
      immunoreactivity observed in ganglion cells (embryonic day 8 [E8] to adult),
      photoreceptor precursors (E8-E12), amacrine cells (E10 to adult), bipolar cells
      (E12-E18), differentiated rods (E18 to adult), and horizontal cells (adult).
      Second, expression is restricted to distinct subpopulations of principal retinal
      neurons: preferentially, large ganglion cells; subpopulations of amacrine cells,
      including a particular type of cholinergic neuron; a distinctly located type of
      bipolar cell; and rod photoreceptors. Third, expression exhibits subcellular
      restriction: it is confined largely to dendrites in mature amacrine cells and is
      restricted entirely to outer segments in mature rods. These data correlate with
      CNTF effects on the survival of ganglion cells and mature photoreceptors, the in
      vitro differentiation of photoreceptor precursors and cholinergic amacrine cells,
      and the number of bipolar cells in culture described here or in previous studies.
      Thus, our results demonstrate an exceptional degree of complexity with respect to
      the regulation of neuronal CNTFR alpha expression in a defined model system. This
      suggests that the same signaling pathway is used to mediate a variety of
      regulatory influences, depending on the developmental stage and cell type.

PMID- 9766403
TI  - Preprocholecystokinin mRNA-expressing neurons in the rat parabrachial nucleus:
      subnuclear localization, efferent projection, and expression of nociceptive
      related intracellular signaling substances.
AB  - The pontine parabrachial nucleus (PB) is a major target for ascending fibers from
      nociresponsive dorsal horn neurons. Several different neuropeptides have been
      identified in the PB. By using double-labeling methods that combine in situ
      hybridization histochemistry with retrograde tract tracing and
      immunohistochemistry, we have examined the subnuclear localization of
      preprocholecystokinin mRNA (ppCCK)-containing neurons, investigated their
      efferent projection, and analyzed their expression of intracellular signaling
      substances that may be of importance for nociceptive processing. The results show
      that neurons containing ppCCK are preferentially localized to the superior
      lateral subnucleus (PBsl), whereas other subnuclei, such as the dorsal lateral,
      external lateral, central lateral, and ventral lateral subnuclei, and the
      Kolliker-Fuse nucleus, contain only moderate to small numbers of such neurons.
      Injections of the retrograde tracer cholera toxin subunit b into the ventromedial
      hypothalamus demonstrated that ppCCK-containing neurons in PBsl were projection
      neurons. Following nociceptive stimulation, the ppCCK-containing neurons
      expressed FOS protein as well as phosphorylated cyclic AMP-responsive element
      binding protein (CREB). In addition, Ca2+/calmodulin-dependent kinase II (CaMKII)
      was heavily and rather selectively expressed in PBsl and was co-localized to
      ppCCK-containing neurons. These observations show that nociceptive stimuli
      activate a cholecystokinin pathway from the parabrachial nucleus to the
      ventromedial hypothalamus that may be important for homeostatic responses to
      tissue damage, and point to a putative intracellular route for Ca2+-mediated FOS
      transcription via CaMKII and CREB for the regulation of ppCCK transcription.

PMID- 9766404
TI  - Thalamocortical connections of the parabelt auditory cortex in macaque monkeys.
AB  - The auditory cortex of macaque monkeys contains a core of primary-like areas
      surrounded by a narrow belt of associated fields that encompass much of the
      superior temporal plane in these animals. Adjacent to the lateral belt on the
      superior temporal gyrus is a parabelt region that contains at least two
      subdivisions (rostral and caudal). In a previous study (Hackett et al. [1998] J.
      Comp. Neurol. 394:475-495), we determined that the parabelt has topographic
      connections with the belt areas surrounding the core, but minimal connections
      with the core itself. In this study, we describe the thalamocortical connections
      of the parabelt auditory cortex based on multiple injections of neuronal tracers
      into this region in each of five macaque monkeys. Injections confined to the
      parabelt labeled large numbers of neurons in the dorsal (MGd) and magnocellular
      (MGm) divisions of the medial geniculate complex (MGC), suprageniculate (Sg),
      limitans (Lim), and medial pulvinar (PM) nuclei. Only when injections encroached
      on the lateral belt cortex were substantial numbers of labeled neurons found in
      the ventral (MGv) division of the MGC, consistent with the absence of significant
      connections between the parabelt and core fields. The rostrocaudal topography of
      the parabelt region was maintained in the thalamocortical connections, supporting
      the parcellation of this region of cortex. The results suggest that the parabelt
      region represents a third level of auditory cortical processing, which is not
      influenced by direct inputs from primary cortical or subcortical auditory
      structures.

PMID- 9766405
TI  - Neurogenesis and migration of receptor neurons in the vomeronasal sensory
      epithelium in the opossum, Monodelphis domestica.
AB  - The sensory epithelium of the vomeronasal organ (VNO) contains primary
      chemosensory receptor neurons that project to the accessory olfactory bulb (AOB).
      In the present study, neurogenesis and cell migration in the sensory epithelium
      of the VNO were analyzed in opossums (Monodelphis domestica) by using
      bromodeoxyuridine (BrdU) labeling. 1) In the VNO of normal adult opossums, BrdU
      labeled a small number of cells localized in the basal region of the sensory
      epithelium. After 1 or 2 weeks of survival, the labeled cells appeared in the
      receptor cell layers and became receptor neurons, as indicated by coexpression of
      the G proteins G(i alpha2) or G(o alpha). 2) In the VNO in which the receptor
      neurons had been destroyed by removing the AOB, the number of BrdU-labeled cells
      in the reconstituting sensory epithelium was greatly increased compared with that
      in the intact VNO. The labeled cells were also located in the basal region of the
      sensory epithelium. 3) In the developing VNO (at postnatal day 10), more cells in
      the basal region of the sensory epithelium were labeled than in the adult VNO,
      indicating rapid cell proliferation; and there appeared to be more labeled cells
      in the basal region near the margins of the sensory epithelium where it meets the
      nonsensory epithelium. These observations demonstrate that, in the opossum VNO,
      there is a population of proliferating cells in the basal region close to the
      basal lamina in the sensory epithelium. The newly generated neurons in the basal
      region migrate vertically into the receptor cell layer.

PMID- 9766406
TI  - Editorial: The jargonic disaster: or whom* wrote that note? 1985.

PMID- 9766407
TI  - Mid-trimester emergent cerclage: a ten year single institution review.
AB  - OBJECTIVE: To evaluate clinical factors associated with both time gained in utero
      and gestational age at delivery in patients undergoing placement of emergent
      cerclages. STUDY DESIGN: Retrospective chart review of 75 patients who underwent
      nonprophylactic cerclages from 1984 to 1994 at Thomas Jefferson University
      Hospital was performed. Clinical variables evaluated included gestational age at
      cerclage, gestational age at delivery, cervical dilation at presentation, and
      presence or absence of bulging membranes on admission. Presence or absence of
      clinical symptoms at presentation or historic risk factors for incompetent cervix
      were also noted. Noncontinuous data were analyzed using chi2 or Fisher's exact
      test; continuous data were compared with either Student's t or Mann-Whitney U
      tests. RESULTS: The mean gestational age at time of cerclage placement was 19.1
      +/- 3.8 weeks, with a median of 12 weeks gained in utero. Overall, 65% of
      patients delivered at > or =28 weeks, with 49% delivering at > or =34 weeks.
      Patients with bulging membranes were more likely to be >2 cm dilated (58% vs. 0%;
      p < 0.001) and to present at > or =20 weeks gestational age (69% vs. 28%; p <
      0.001). They also gained less time after cerclage placement (median 6.4 vs. 17.0
      weeks; p < 0.001) and were less likely to reach either 28 weeks (44% vs. 85%; p <
      0.001) or 34 weeks (31% vs. 67%; p = 0.004) at delivery. CONCLUSION: The presence
      of bulging membranes or advanced dilation at presentation was associated with
      lower cerclage-to-delivery intervals as well as a lower chance of reaching 28
      weeks of gestation.

PMID- 9766408
TI  - The association of aneuploidy and unexplained elevated maternal serum alpha
      fetoprotein.
AB  - OBJECTIVE: The purpose of this study was to examine fetal chromosomal
      abnormalities in pregnancies complicated by unexplained elevated maternal serum
      alpha-fetoprotein (MSAFP). STUDY DESIGN: We reviewed, using a computerized
      database, 58,162 obstetrical ultrasounds that were performed for various
      indications. Fetuses with MSAFP multiples of the median (MOM) > or = 2.5 and
      normal extensive ultrasounds were identified. Maternal demographic data and fetal
      karyotype were obtained. RESULTS: Seven hundred eighty-nine patients received
      ultrasounds for evaluation of elevated MSAFP. Of the 595 patients with normal
      scans, 195 (32.8%) underwent amniocentesis and cytogenetic evaluation. Two
      chromosomal abnormalities were detected (1.0%), including an inversion and a
      balanced translocation. CONCLUSION: The two karyotypic abnormalities identified
      in our study consisted of structural rearrangements. Patients undergoing
      karyotype analysis for unexplained elevated MSAFP should be counseled that the
      types of aneuploidy detected under this circumstance differ from those associated
      with advanced age and specific fetal anomalies (trisomy and triploidy).

PMID- 9766409
TI  - Impact of the perception of viability on resource allocation in the neonatal
      intensive care unit.
AB  - OBJECTIVE: To understand how neonatologists' perceptions of viability impact
      their willingness to recommend or provide medical interventions for infants born
      at 23 to 24 weeks' gestation. STUDY DESIGN: A 25-question survey mailed to 3056
      neonatologists in the United States in 1992 yielded 1131 responses. Seven hundred
      seventy-five (775 of 1131, 69%) reported they believed that the lower limit of
      viability was 23 to 24 weeks' gestation. These respondents were asked if they
      were willing to recommend or provide a series of medical interventions for
      infants born at 23 and 24 weeks' gestation. RESULTS: Most respondents would
      provide ventilation (82% and 95%) and surfactant (62% and 78%) for infants born
      at 23 and 24 weeks' gestation, respectively. The respondent's prediction of <100%
      mortality, infant factors, and parental wishes were significant predictors of
      willingness to resuscitate infants born at 23 weeks' gestation. CONCLUSION: There
      is considerable variation among neonatologists in their willingness to recommend
      or provide medical interventions for infants born at 23 to 24 weeks' gestation.

PMID- 9766410
TI  - Randomized trial of magnesium administration to prevent hypocalcemia in infants
      of diabetic mothers.
AB  - OBJECTIVE: Hypocalcemia is common in infants of diabetic mothers (IDMs) and may
      be caused by secondary hypoparathyroidism related to hypomagnesemia. This study
      was designed to test the hypothesis that prophylactic magnesium sulfate (MgSO4)
      administration at birth in IDMs with low cord magnesium concentrations will
      prevent neonatal hypocalcemia. STUDY DESIGN: In this randomized trial conducted
      in IDMs with a cord magnesium concentration of <0.74 mM (1.8 mg/dl), 26 subjects
      received 6 mg/kg elemental magnesium and 23 subjects received no treatment. Serum
      concentrations of total and ionized calcium, phosphorus, and magnesium were
      recorded at birth, by measuring the concentrations within the umbilical cord, and
      at 24 and 72 hours of age. RESULTS: The incidence of hypocalcemia at 72 hours was
      0% (0 of 23) in the magnesium-treated group and 12.5% (2 of 16) in the group with
      no treatment (p = 0.16). There was no difference in mean serum calcium
      concentration at 72 hours between infants in the treated group and the group with
      no treatment (2.28 +/- 0.04 vs 2.22 +/- 0.05 mM; p = 0.39). The drop in serum
      calcium concentration from birth to 72 hours of age was less for the treated
      group (0.30 +/- 0.05 mM [1.23 +/- 0.18 mg/dl]) than the group with no treatment
      (0.45 +/- 0.05 mM [1.81 +/- 0.21 mg/dl]; p = 0.04). CONCLUSION: Administration of
      intramuscular MgSO4 to IDMs with cord magnesium <0.74 mM (1.8 mg/dl) does not
      reduce the incidence of hypocalcemia in infants of well-controlled diabetic
      mothers.

PMID- 9766411
TI  - Dose-dependent evaluation of the effects of nebulized furosemide on pulmonary
      function in ventilated preterm infants.
AB  - OBJECTIVE: We have previously shown that a single dose of nebulized furosemide
      improves tidal volume and pulmonary compliance for up to a 2-hour study period.
      This study is undertaken in order to find out (a) whether increasing the dose of
      nebulized furosemide from 1 to 2 mg/kg of body weight will further improve the
      pulmonary mechanics in premature infants with evolving chronic lung disease and
      (b) whether the effects of a single dose of nebulized furosemide last beyond 2
      hours. STUDY DESIGN: The effect of nebulized furosemide on pulmonary mechanics
      was studied at a mean postnatal age of 24 days (range 14 to 50 days) in 13
      premature infants, 24 to 28 weeks' gestational age, who had been dependent on
      mechanical ventilation since birth. Furosemide was administered by nebulization
      at doses of 1 and 2 mg/kg of body weight, in random order, on two separate days
      24 hours apart. Pulmonary function studies were performed before and 2, 4, and 6
      hours after the nebulization. Urine was collected for 6 hours immediately before
      and for 6 hours after the nebulization. RESULTS: Furosemide by nebulization at 1
      and 2 mg/kg of body weight resulted in significant improvement in tidal volume
      and compliance. There was no difference in the magnitude of response between the
      two doses. Neither 1 nor 2 mg/kg of body weight of nebulized furosemide had any
      effect on airway resistance. The improvement was maximum for up to 4 hours and
      lasted for up to 6 hours after the nebulization and was not associated with
      diuresis or increased excretion of urinary electrolytes. CONCLUSION: A single
      dose of nebulized furosemide improves pulmonary function for up to 6 hours after
      its administration. Increasing the dose from 1 to 2 mg/kg of body weight results
      in no further improvement in the pulmonary function. The pulmonary effects of
      nebulized furosemide are independent of its diuretic action.

PMID- 9766412
TI  - Peak noise distribution in the neonatal intensive care nursery.
AB  - OBJECTIVE: To measure short duration sounds (L(PEAK)) in the neonatal intensive
      care unit and describe their intensity, incidence, and periodicity in
      relationship to activities within the unit. STUDY DESIGN: We measured 1-minute
      L(PEAK) at four locations within the intensive care unit, accumulating 48 hours
      of data for each weekday. RESULTS: Thirty-one percent of the L(PEAK) exceeded 90
      dB. For further analysis, the data were transformed to the proportion exceeding
      90 dB. These values varied significantly with day, week, location, and time of
      day. During physician rounds, there was a 16% relative increase in L(PEAK).
      CONCLUSION: These data demonstrate the intensity, incidence, and periodicity of
      short duration sounds in the intensive care nursery. Short duration sounds are
      known to affect the infant's physiological and behavioral states and should be
      addressed in future recommendations for sound control and reduction strategies.

PMID- 9766413
TI  - Very low birth weight infants and their families during the first year of life:
      comparisons of medical outcomes based on after care services.
AB  - OBJECTIVE: To evaluate factors contributing to optimal medical outcomes during
      the first year following discharge of very low birth weight infants from tertiary
      neonatal intensive care units. STUDY DESIGN: This was a prospective investigation
      of the health and development of 81 very low birth weight infants following
      discharge from two tertiary neonatal intensive care units in Los Angeles. Infants
      were assigned to four groups receiving a variety of after care services in their
      homes. Analyses of variance were computed to examine differences between groups
      for a variety of outcomes. RESULTS: No statistically significant differences were
      seen between after care groups on use of hospital emergency rooms (ER)
      rehospitalization rates, or child abuse and neglect. Highest overall rates of
      optimal outcomes were seen in the group receiving the highest intensity of after
      care services. Those groups receiving long-term home visiting services had
      significantly higher rates of up-to-date immunizations. CONCLUSION: There was no
      significant impact on infant mortality and morbidity of early discharge,
      regardless of the system of after care used. However, those infants who received
      the highest level of after care services had the most optimal health outcomes and
      were most likely to be receiving well-baby care. It is likely that the
      comprehensive, clinic-based system of health care available to all study infants
      was a significant factor in low rates of morbidity.

PMID- 9766415
TI  - The value of standard electroencephalograms in the evaluation of the newborn with
      recurrent apneas.
AB  - OBJECTIVE: To determine the usefulness of the standard electroencephalograms in
      the evaluation of prematurely born infants admitted to a neonatal intensive care
      unit with recurrent apneas and bradycardias. STUDY DESIGN: Retrospective review.
      RESULTS: During the study period, 94 infants were evaluated for seizure activity.
      Twenty of these were prematurely born infants with recurrent apneas and
      bradycardias without clinically recognized seizures. The recordings were entirely
      normal in 10 cases, and in 9 showed interictal epileptiform discharges in excess
      of or in atypical locations than those expected for the gestational age at the
      time of the investigation. One had an abnormal electroencephalogram (EEG) pattern
      with episodes of generalized flattening occurring repeatedly throughout the
      entire recording. None had electrographic seizures. All infants were free of
      sepsis and gastroesophageal reflux and all had normal biochemistry at the time of
      the EEG recordings. CONCLUSION: In our study, routine EEG was not found to be
      useful in the investigation and management of prematurely born infants with
      recurrent apneas not associated with clinically recognized seizure activity.

PMID- 9766416
TI  - Use of abnormalities in the Friedman curve as a predictor of operative delivery
      in macrosomic babies.
AB  - OBJECTIVE: To assess the use of the Friedman labor curve as a predictor of
      operative delivery in macrosomic pregnancies. STUDY DESIGN: Medical records of
      1141 patients who had delivered babies > or =4000 gm (group 1) were reviewed and
      were compared with the results of the next mother who delivered a neonate with
      birth weight <4000 gm (group 2). The variables studied were progress of labor as
      denoted on the Friedman curve, oxytocin use, and need for operative delivery.
      RESULTS: In the 1141 patients with neonatal birth weights > or =4000 gm, there
      was a trend toward a longer second stage, arrest disorder, and operative delivery
      but this did not reach statistical significance. CONCLUSION: Abnormalities in the
      Friedman curve were not useful as a predictor for operative delivery in
      pregnancies complicated by fetal macrosomia. There were no statistically
      significant differences between the two groups in terms of the variables studied.

PMID- 9766414
TI  - Frequency, timing, and diagnoses of antenatal hospitalizations in women with high
      risk pregnancies.
AB  - OBJECTIVE: To examine the frequency, time of gestation, and reasons for antenatal
      hospitalizations in women with medically high-risk pregnancies. STUDY DESIGN:
      This secondary analysis reports all antenatal hospitalizations from a clinical
      trial testing transitional care to women with high-risk pregnancies. Data were
      collected from 1992 to 1996. Pregnant women with pregestational (n = 16) or
      gestational diabetes (n = 21), hypertension (n = 29), and diagnosed (n = 47) or
      at high risk for preterm labor (n = 37) were included. Diagnoses for each
      hospitalization and lengths of stay were collected from chart review and
      validated by attending physicians. Gestation was determined via ultrasonography.
      The sample (N = 150) consisted of predominantly African-American women, never
      married, between the ages of 15 and 40 with Medicaid insurance. RESULTS: Eighty
      three percent (n = 125) of the women had one or more antenatal hospitalization
      with a mean length of stay of 123 hours. All women with diabetes were
      hospitalized at least once. Women with pregestational diabetes had the greatest
      number of hospitalizations whereas those with gestational diabetes had the least.
      Major reasons for hospitalizations were preterm labor, glucose control, premature
      cervical dilation, and preeclampsia. CONCLUSION: Some hospitalizations could
      potentially be avoided or reduced through expanded patient education, improved
      screening, and more aggressive monitoring for early signs and symptoms of
      impending complications.

PMID- 9766417
TI  - Examining the "cost" of substance abuse in pregnancy: patient outcomes and
      resource utilization.
AB  - OBJECTIVE: This study investigated the clinical and financial impact of self
      reported maternal drug history and documented intrauterine substance exposure on
      maternal-neonatal morbidity and hospital costs. STUDY DESIGN: This two-part, case
      controlled, retrospective study used matching control groups. RESULTS: Among
      women reporting a history of substance abuse during or prior to the index
      pregnancy, (a) maternal hospital costs were significantly higher and more
      variable; (b) birth weight, length, and gestational age were lower; (c) no
      significant differences were noted in the number of maternal risk factors or
      neonatal complications and hospital costs. In comparison of neonates with
      positive toxicology screens and a matched control group, there were no
      differences in neonatal outcomes or costs, but the number of complicating
      maternal risk factors and maternal hospital costs were significantly different.
      CONCLUSION: Knowledge of maternal substance abuse history may be useful in
      planning for maternal-neonatal care needs and reimbursement for hospital care for
      this at-risk patient population.

PMID- 9766419
TI  - Prenatal diagnosis and clinical features of an individual with tetrasomy 18p and
      trisomy 18q mosaicism.
AB  - Prenatal diagnosis and clinical follow up of a patient with mosaicism for
      anomalies of chromosome 18 are reported. The fetus appeared on ultrasound to have
      multiple anomalies, including clubbed feet, abnormal hand positioning, edema of
      the scalp, cleft palate, and polyhydramnios. The karyotype on amniocytes was
      47,XY,+i(18p). Postnatally, the peripheral blood karyotype was 46,XY,+i(18q),
      whereas the skin fibroblast karyotype was 47,XY,+i(18p). The infant had many
      features consistent with those previously described in cases of tetrasomy 18p and
      some that were consistent with trisomy 18q.

PMID- 9766418
TI  - Congenital and perinatal tuberculosis: discussion of difficult issues in
      diagnosis and management.
AB  - Tuberculosis (TB) has become more prevalent in women of childbearing age and, as
      well, more frequent in their children. This has occurred for a number of reasons,
      including: (1) women and children who have immigrated to this country from areas
      where TB is endemic, such as Mexico and Southeast Asia; (2) the development of
      multidrug-resistant organisms; (3) the increase seen in patients who live in
      congregate areas who are at higher risk for acquisition of TB; (4) more difficult
      access to adequate medical care; and (5) increases in adults and children who
      have become infected with human immunodeficiency virus. The focus of this review
      is on congenital and perinatally acquired TB including discussion of
      epidemiology, the stages of TB, the effects of TB infection and disease during
      pregnancy on the fetus and mother, congenital and perinatal TB, the potential
      role of the use of BCG vaccine in infants, and the emergence of multidrug
      resistant TB on therapy of the pregnant mother and her fetus and the mother and
      her infant after delivery.

PMID- 9766420
TI  - "Pseudo" twin-to-twin transfusion syndrome and fetal outcome.
AB  - OBJECTIVE: To assess the fetal outcome, in a tertiary center, in pregnancies with
      suspected twin-to-twin transfusion syndrome (TTTS) not confirmed using
      ultrasonographic examination, diagnosis of pathology, or both. STUDY DESIGN:
      Forty-four pregnancies with suspected TTTS were followed longitudinally using
      ultrasonographic examination until delivery. The minimal criteria for the
      diagnosis of TTTS were: (1) suspicion of monochorionicity gleaned from ultrasound
      examination (to be confirmed at birth); (2) presence of polyhydramnios in one
      gestational sac (either assessed subjectively--or, finding that the largest
      vertical pocket of amniotic fluid was >8 cm in diameter before 20 weeks'
      gestation and >10 cm in diameter thereafter); and (3) presence of oligohydramnios
      in the other gestational sac (finding either that there was a "stuck" twin
      complication or that the largest vertical pocket of amniotic fluid was <1 cm in
      diameter). When one of the above criteria was not present, the pregnancy was
      defined as "pseudo" TTTS. Fetal outcome in "pseudo" TTTS was analyzed according
      to the relative size of the neonate (large or small) and whether the cord
      insertion was normal or velamentous. RESULTS: There were 18 cases of "pseudo"
      TTTS. No treatment in utero was necessary in any of the 18 pregnancies. The mean
      gestational age was 21.9 +/- 3.7 (1 SD) weeks at diagnosis and 33.0 +/- 3.0 weeks
      at delivery. The average weight discrepancy between the twins at birth was 34.3
      +/- 14.8%. There were three fetal demises of the small twin and one neonatal
      demise of the large twin (p > 0.05). Large twins developed respiratory distress
      syndrome (RDS) more often than small twins (p < 0.05). Five percent of the large
      twins and 50% of the small twins had a velamentous insertion of the cord (p <
      0.05). CONCLUSION: In pregnancies complicated by "pseudo" TTTS our data indicate
      that: (1) small twins have abnormal cord insertion more frequently than large
      twins, (2) large twins develop RDS more frequently than small twins. Our data
      suggest that the perinatal mortality in these pregnancies appears to be lower
      than that reported for the classical TTTS.

PMID- 9766421
TI  - Fetal heart rate monitoring casebook. Benign recurrent late decelerations.

PMID- 9766422
TI  - Special imaging casebook. Neonatal malignant rhabdoid tumor of the kidney.

PMID- 9766423
TI  - Neonatal transport: a protocol for ambulance transfer to a neonatal intensive
      care unit.

PMID- 9766424
TI  - Endotracheal tolazoline administration in neonates with persistent pulmonary
      hypertension.

PMID- 9766425
TI  - Introduction to histological and histochemical aspects of wound healing.

PMID- 9766426
TI  - Analysis of extracellular matrix synthesis during wound healing of retinal
      pigment epithelial cells.
AB  - To investigate changes in retinal pigment epithelial (RPE) cells during wound
      healing, we evaluated the deposition of newly synthesized extracellular matrix
      (ECM) over time during wound healing in rat RPE cultures. We also estimated the
      effect of growth factors on the healing rate and ECM synthesis. After preparing
      rat RPE cell sheet cultures, we made round 1-mm defects in the cultures.
      Fibronectin, laminin, and collagen IV synthesis were evaluated with
      immunocytochemistry every 12 hours after wounding. S-phase cell distribution was
      analyzed every 12 hours by 5-bromodeoxyuridine uptake. We added either platelet
      derived growth factor (PDGF), epidermal growth factor (EGF), or transforming
      growth factor- beta2 (TGF-beta2) to cultures at concentrations of 1, 10, and 100
      ng/mL and immunocytochemically analyzed the effects on ECM and estimated the rate
      of wound closure. Although approximately 50% closure was achieved 24 hours after
      wounding, fibronectin deposits first appeared at that time. Laminin and collagen
      IV were first detected at 36 hours and fibronectin staining had extended toward
      the wound center. S-phase cells were distributed in concentric rings that moved
      centripetally over time and corresponded to the leading edge of the area stained
      with anti-ECM antibodies. TGF-beta2 enhanced ECM deposition, but EGF and PDGF did
      not. TGF-beta2 decreased the healing rate in a dose-dependent manner, whereas
      PDGF promoted wound closure. EGF enhanced closure at the highest concentration
      only. In summary, wound healing in RPE may be initiated when cells at the wound
      edge slide or migrate toward the wound center, which is followed by cell
      proliferation and then ECM synthesis. ECM components may be produced in a
      specific sequence during healing. TGF-beta2 may promote RPE cell differentiation,
      and PDGF may enhance proliferation during wound healing of the RPE.

PMID- 9766427
TI  - Understanding and controlling the scarring response: the contribution of
      histology and microscopy.
AB  - In response to injury, the body usually initiates a full and swift wound healing
      response resulting in reconstructed, repaired tissue. In certain instances, due
      to a variety of factors, this may not happen, an example being chronic
      granulating venous leg ulcers. At the other extreme, the wound may heal
      excessively, producing disabling hypertrophic scarring such as can occur
      following large, deep burn injuries. Our group is interested in the surgical
      treatment of the eye disease glaucoma. As will be explained, the successful
      surgical treatment of this disease depends on a reduced scarring response at the
      end of wound healing. The purpose of this article is to give an overview of our
      microscopic and histological experimental work which has furthered our
      understanding of tissue repair, particularly the scarring response and its
      potential modification for successful glaucoma surgery.

PMID- 9766428
TI  - Ultrastructural and cytochemical study of neurones in the rat dorsal motor
      nucleus of the vagus after axon crush.
AB  - The cell populations in the dorsal motor nucleus of the vagus (DMNV) of the rat
      were studied by light microscopy and transmission electron microscopy, including
      retrograde labeling with horseradish peroxidase and histochemical demonstration
      of the distribution of the activity of the enzymes acetylcholinesterase (AcChE)
      and butyrylcholinesterase (BuChE). Two types of neurones were observed: 1) Larger
      Type A cells, which stain for both AcChE and BuChE and which project into the
      vagus nerve trunk, and 2) smaller Type B cells, which stain lightly for AcChE but
      not for BuChE and which do not project into the vagus nerve. Standardised vagal
      crush at the mid-cervical level causes loss of cholinesterase activity in Type A
      neurones within a few days but has no effect on Type B neurones. Changes in
      nuclear morphology of Type A neurones are pronounced at 10 weeks postinjury,
      indicating that degeneration is irreversible even by this stage. The number of
      Type A cells projecting to the vagus nerve reduces as a function of time,
      presumably as these cells die. Only a small number of Type A neurones persist at
      2 years postinjury.

PMID- 9766429
TI  - Modeling of wound healing processes in human skin using tissue culture.
AB  - To facilitate the investigation of the complex process that leads to healing of a
      human skin wound we developed standardized and repeatable in vitro models for
      both incisional and burn wounds. Wounds with a standardized area and depth were
      created in normal human skin biopsies which were then incubated in vitro. It was
      shown, by cultivation, that both dermal and epidermal cells maintained their
      viability during a 14-day in vitro incubation if exposed to at least 2% fetal
      calf serum. By incubating in 10% serum, the skin samples were stimulated to
      completely re-epithelialize the wounded area. Because a large number of
      standardized wounds can be obtained from each donor, the re-epithelialization
      process can be studied histologically and immunohistochemically at several
      adjacent time points. The ability to keep the cells in the wound area viable
      without stimulating healing by incubating the wounds in suboptimal serum
      concentrations implies a way of studying the stimulatory effects of different
      agents, such as growth factors, on the wound healing process. There were some
      marked discrepancies in the healing process between the incisional and burn
      wounds which resemble the in vivo situation, indicating that the in vitro models
      could be used to more closely study differences between healing in different
      types of wounds. Our findings suggest that in vitro tissue culture can be of
      great value in attempting to better understand the complex process of wound
      healing in human skin.

PMID- 9766430
TI  - A microscopical study of wound repair in the human placenta.
AB  - In order to fulfill its many functions as the selective interface between
      maternal and fetal circulations it is imperative that the human placenta remains
      intact and in good operational order. That damage of some sort occurs during its
      short but extremely active life seems inevitable given the dynamic environment in
      which the placenta exists, and evidence has accumulated that disruption is indeed
      a regular event. The implications of such damage, one could speculate, may impact
      on functions such as transport and hormone secretion as well as mutual protection
      against attack by maternal and fetal immune systems. Consequently, it would seem
      a theoretical necessity for discontinuities in the placenta surface to be
      repaired as soon as possible. We have used a combination of ex vivo observation,
      in vitro modelling, immunohistochemistry and correlative microscopy to provide
      evidence for a wound response in the placenta and to begin dissecting the detail
      of how this may operate. Evidence for small lesions caused by fusion and
      subsequent tearing of the syncytiotrophoblast in vivo, as well as plugging of
      such wounds by underlying cells is shown. We also identify a putative role for
      migratory cytotrophoblasts in the healing of larger scale injuries and
      demonstrate that certain molecules, common to wound repair in other tissues,
      appear to be involved in placenta repair also. Taken together these results
      clearly show that the human placenta is capable of a degree of self-maintenance
      by activating what appears to be an endogenous wound healing mechanism.

PMID- 9766431
TI  - Cytochemical demonstration of sites of hydrogen peroxide generation and increased
      vascular permeability in isolated pig hearts after ischaemia and reperfusion.
AB  - Isolated pig hearts, subsequently perfused with pig or human blood, were prepared
      for the cytochemical demonstration of sites of hydrogen peroxide generation and
      increased vascular permeability. Oxidant stress was associated with
      ultrastructural changes commonly seen following myocardial reperfusion. In
      addition, the precipitation of cerium perhydroxide following perfusion with
      physiological saline containing cerium chloride suggested the vascular
      endothelium and leukocytes as sources of oxidants. This was associated with rapid
      penetration of horseradish peroxidase through the intercellular clefts of the
      vascular endothelium into the interstitial space, suggesting increased vascular
      leakiness at these sites. The rapid penetration of horseradish peroxidase was
      observed at all monitored periods of reperfusion with pig or human blood. This
      indicates that the increased permeability occurred during the ischaemic period
      and continued during reperfusion. Morphological damage was greatest in pig hearts
      reperfused with whole human blood and this was attenuated if the blood was
      preabsorbed to remove antibodies prior to reperfusion. We conclude that oxidant
      stress was initiated during ischaemia and continued during reperfusion in this
      model.

PMID- 9766432
TI  - Relaxed cell-cycle arrests and propagation of unrepaired chromosomal damage in
      cancer cell lines with wild-type p53.
AB  - The role of the p53 protein in mediating G1 and G2 cell-cycle arrests after
      genotoxic insult has been clearly and reproducibly established in primary diploid
      fibroblasts, but data obtained from p53 wild-type (wt) cancer cell lines are
      inconsistent. Furthermore, a large proportion of human tumors have p53 wt
      genotypes but present genetic aberrations that may result from defective cell
      cycle checkpoints. We therefore investigated the integrity of G1/S and G2/M cell
      cycle arrests in p53 wt cancer cell lines. In the study presented here, we showed
      that in most cancer cells tested, G1 arrest was relaxed or absent in comparison
      with arrest in normal diploid fibroblasts, despite seemingly normal p53 and p21
      responses. Two cell lines (MCF7 and HCT116) were synchronized in G0/G1 by leucine
      starvation and subjected to genotoxic stress to determine more precisely the
      relative proportion of cells arresting in G1 and G2. Whereas the MCF7 cells
      showed consistent G1 arrest, the HCT116 cells showed none at all. Furthermore,
      cell-cycle arrests in G1 and G2 in response to gamma irradiation and bleomycin
      treatment were transient, as the cells resumed cycling after 48-72 h. The cells
      resuming proliferation suffered massive apoptosis, but a proportion of the cells
      were rescued and showed normal doubling times. These cells retained a p53 wt
      genotype but presented gross chromosomal aberrations in 15-20% of the analyzed
      metaphases. The aberrations were not clonal. These data show that p53 wt cancer
      cells have relaxed cell-cycle controls after genotoxic insult and tolerate
      unrepaired chromosomal damage, despite normal p53 function.

PMID- 9766433
TI  - Androgen regulation of the human pseudoautosomal gene MIC2, a potential marker
      for prostate cancer.
AB  - Using the differential display-polymerase chain reaction technique to identify
      androgen-responsive genes in the human prostatic tumor cell line LNCaP, we cloned
      an expression tag homologous to the human pseudoautosomal gene MIC2. The role of
      MIC2 in the prostate had not previously been studied. We used a series of cell
      lines derived from LNCaP that varied in their degree of differentiation and
      metastatic potential to assess the relationship between MIC2 expression and
      androgen responsiveness in prostate cancer. The expression of MIC2 mRNA and its
      product E2 was upregulated by androgen in a dose- and time-dependent manner in
      the parental LNCaP line and correlated with the expression of prostate-specific
      antigen. In the LNCaP sublines and an androgen-repressed invasive human prostate
      cancer cell line (ARCaP), MIC2 gene expression was not regulated by androgen and
      was associated with poorer differentiation, decreased androgen sensitivity, and
      higher metastatic potential. Immunohistochemical analyses indicated that E2 was
      expressed in tissues from patients with primary prostate cancer (16 of 20), in
      fetal prostatic tissues (low levels in all 10 fetal tissues assessed), and
      sporadically in benign prostatic hyperplasia tissues (one of four). The normal
      prostate tissues did not show positive E2 staining, with the exception of one
      central-zone section from one of the eight normal prostate samples assessed.
      These findings suggest that deregulation of expression of the human
      pseudoautosomal gene MIC2 occurred in the prostate.

PMID- 9766434
TI  - Malignant transformation of simian virus 40-immortalized human milk epithelial
      cells by chemical carcinogenesis accompanied by loss of heterozygosity on
      chromosome 1 but not microsatellite instability.
AB  - Simian virus 40-immortalized human milk epithelial cells (HuMI) are anchorage
      dependent and non-tumorigenic but can spontaneously progress to anchorage
      independent and tumorigenic cells. To see whether HuMI cells can be transformed
      into anchorage-independent cells by chemical carcinogens, we treated them with 3
      methylcholanthrene (MCA, 10 microg/mL). After 7-8 wk of culture, none of the
      treated cells grew in soft agar. However, when HuMI cells treated with MCA were
      cultured with 12-O-tetradecanoylphorbol-13-acetate (TPA, 10 ng/mL), they grew in
      soft agar; cells treated with TPA alone did not. TPA at this dose was cytotoxic
      to HuMI cells but not to their tumorigenic subline HuMI-TTu2. The response of the
      anchorage-independent HuMI-T cells was intermediate. These results indicate that
      HuMI cells can be transformed by treatment with MCA plus TPA, possibly because
      TPA selects those cells that are progressing toward malignancy. All five clones
      from MCA plus TPA-induced transformed cells formed malignant carcinomas in nude
      mice. When microsatellite changes at 17 loci in HuMI, HuMI-T, HuMI-TTu2, and five
      MCA plus TPA-transformed cells were examined, none of these cell lines showed
      instability at any locus, and no change in microsatellite length was found.
      However, all five MCA plus TPA-transformed cell lines showed loss of
      heterozigosity at 1q21-23 and 1q42 loci. This region of chromosome 1 is known to
      contain at least one antiproliferative gene, and our results suggest that
      inactivation of such a gene may be essential for full transformation of HuMI
      cells by chemical carcinogens.

PMID- 9766435
TI  - Induction of growth inhibition of 293 cells by downregulation of the cyclin E and
      cyclin-dependent kinase 4 proteins due to overexpression of TIS21.
AB  - We earlier reported that TIS21 mRNA expression was markedly decreased in A549 and
      NCIH69 human lung cancer cells and in thymic carcinoma tissues obtained from
      transgenic mice containing simian virus 40 large T antigen (J Cancer Res Clin
      Oncol 121:279-284, 1995). To determine how TIS21 inhibits growth, we made 293
      cells that constitutively expressed TIS21 protein. The constitutive TIS21
      expresser lines C9 and C11 grew to a lower saturation density than did those in
      the vector-transfected clones (V7 and V10) and antisense-transfected clones (AS1
      and AS4), and the size of the C9 and C11 cells increased significantly after
      transfection with TIS21 cDNA. The serum-stimulated cell cycle was analyzed by
      fluorescence-activated cell sorting after double thymidine treatment; V10
      progressed normally through the cell division cycle, but C9 and C11 cells
      accumulated continuously in G1 phase until 36 h after treatment. On the other
      hand, the progression of cells that had already entered to S or G2/M phase was
      not inhibited. When cell-cycle regulatory proteins were measured, C9 and C11
      cells showed significantly reduced synthesis of cyclin E and cyclin-dependent
      kinase (cdk) 4 as well as a decrease in cyclin E-associated cdk activity. These
      observations led us to conclude that TIS21 overexpression in G1 phase decreased
      the amounts of cyclin E and cdk4, thereby decreasing the activity of cdks at the
      G1-S transition.

PMID- 9766437
TI  - Skin tumorigenesis and Ki-ras and Ha-ras mutations in tumors from adult mice
      exposed in utero to 3'-azido-2',3'-dideoxythymidine.
AB  - This study was designed to evaluate the potential initiating effects of
      transplacental 3'-azido-2',3'-dideoxythymine (AZT) and the role of ras mutational
      activation in skin tumors induced in a two-stage mouse skin model. In addition,
      mouse liver and lung tumors from a transplacental AZT tumorigenicity study
      reported elsewhere (Olivero et al., J Natl Cancer Inst 89:1602-1608, 1997) were
      examined for evidence of ras activation. For both tumor studies, pregnant CD-1
      mice were given either vehicle or 25 mg of AZT daily on days 12-18 of gestation.
      In the 1997 study, the offspring were given no further exposure and were killed
      at 1 yr of age. For the skin tumor study, all mice received twice-weekly topical
      12-O-tetradecanoyl-phorbol-13-acetate (TPA) treatment from weeks 5-35; half of
      the mice had been exposed to AZT in utero. At weeks 16-18, 30, 31, and 34-41, the
      skin tumor incidences in mice given AZT and TPA were significantly higher than in
      mice given TPA alone (P < or = 0.05). At week 41, the average numbers of tumors
      per mouse were 1.44+/-0.36 (mean +/- standard error of the mean) and 0.57+/-0.13
      for mice given AZT plus TPA and TPA alone, respectively (P = 0.006). Mutagenesis
      in ras exons I and II was determined by polymerase chain reaction (PCR) and dye
      terminator cycling sequencing of PCR products. Ha-ras exon I codons 12 and 13
      were mutated in 11 of 19 tumors (58%) from mice given AZT and TPA and in one of
      15 tumors (7%) from mice given TPA alone (P= 0.004). The only mutation in Ha-ras
      codon 12 (four in four tumors examined) was a G-->A transition in the second
      base, and the major mutation in codon 13 (six in seven tumors examined) was a G-
      >T transversion in the second base. In skin tumors, AZT exposure did not increase
      the number of Ha-ras codon 61 mutations, and no Ki-ras mutations were observed.
      Analysis of ras mutations in liver and lung tumors from mice exposed to AZT in
      utero (Olivero et al., J Natl Cancer Inst 89:16021608, 1997) with no TPA
      promotion showed no significant AZT-related increases.

PMID- 9766436
TI  - Localization of prostaglandin H synthase isoenzymes in murine epidermal tumors:
      suppression of skin tumor promotion by inhibition of prostaglandin H synthase-2.
AB  - The growth factor- and phorbol ester-inducible prostaglandin H synthase (PGHS)-2
      has been found to be constitutively overexpressed in epidermal tumors generated
      by the initiation-promotion protocol in murine skin, whereas the expression of
      PGHS-1 does not change under these conditions. In this paper we report the intra
      tumor distribution of the aberrantly expressed PGHS-2 and the cancer
      chemopreventive activity of a specific PGHS-2 inhibitor. By immunohistochemical
      methods using isoenzyme-specific antibodies, we found that the PGHS-1 protein was
      expressed in keratinocytes and Langerhans cells dispersed throughout the
      epithelial part of papillomas and squamous cell carcinomas and in inflammatory
      infiltrates occasionally seen in these tumors. A uniform pattern of PGHS-2
      expression was observed in the basal keratinocytes of papillomas and in the
      follicular keratinocytes of carcinomas. In addition, Langerhans cells as well as
      tumor-associated inflammatory infiltrates exhibited PGHS-2-specific
      immunoreactivity. PGHS-2-catalyzed prostaglandin synthesis stimulated by the
      phorbol ester 12-O-tetradecanoylphorbol-13 acetate (TPA) in mouse epidermis in
      vivo was dose-dependently suppressed by topical administration of SC-58125, a
      specific PGHS-2 inhibitor. TPA-induced edema formation, epidermal DNA synthesis,
      and mitotic activity were not impaired by SC-58125 applied at a dose that
      inhibited TPA-induced prostaglandin E2 synthesis. However, the repetitive
      epicutaneous administration of SC-58125 substantially and significantly
      suppressed papilloma development. Malignant progression of papillomas was
      slightly retarded by the drug. These results indicate that aberrant expression of
      PGHS-2 in epidermal tumors may be a relevant target for prevention of epidermal
      cancer development in experimental animals and that the PGHS-2-specific inhibitor
      SC-58125, which is a potent inhibitor of tumor promotion in mouse skin, may be
      important for cancer chemoprevention in humans as well.

PMID- 9766438
TI  - Is excessive spontaneous intramedullary apoptosis unique to myelodysplasia?

PMID- 9766439
TI  - While waiting for Christopher Columbus to discover alternative route(s) of bone
      marrow regulation, keep faith the body is a global system.

PMID- 9766440
TI  - Regulation of erythropoiesis by bone marrow reninangiotensin system: facts and
      speculations.

PMID- 9766441
TI  - CD34- stem cells as the earliest precursors of hematopoietic progeny.

PMID- 9766442
TI  - Serum of healthy donors receiving granulocyte colony-stimulating factor induces T
      cell unresponsiveness.
AB  - The effects of serum from healthy donors receiving recombinant human granulocyte
      colony-stimulating factor (rhG-CSF) (G-serum) on blast transformation, expression
      of activation-related antigens, secretion of interleukin (IL)-2, and
      proliferation were evaluated in allogeneic lymphocytes stimulated with
      phytohemagglutinin. Escalating concentrations of G-serum induced 27%, 47%, and
      70% suppression of lymphocyte proliferation; interestingly, CD4+ and CD8+ cells
      underwent blast transformation and up regulated early (CD69) and late (CD25, HLA
      DR, and CD71) activation-related antigens. Negligible fractions of apoptotic
      cells were found after mitogenic challenge, suggesting that the strongly
      diminished proliferation was not attributable to extensive activation-induced
      programmed cell death of responding T cells. The levels of IL-2 in cultures
      containing G-serum were comparable to those in cultures performed without G
      serum; however, high concentrations of exogenous IL-2 restored lymphocyte
      mitogenesis regardless of G-serum concentration. These findings--cell
      enlargement, upregulation of activation-related antigens, inability to
      proliferate after mitogenic stimulus, and restoration of cell division by
      exogenous IL-2--resembled those associated with "partial activation" of
      lymphocytes, a fundamental control mechanism of tolerance induction in T cell
      clones. Soluble immunoregulatory mediators infused with allogeneic hematopoietic
      progenitor products collected after rhG-CSF administration could induce T cell
      unresponsiveness in vivo, thus preventing clonal expansion and amplification of
      immune responses, and could account for the unexpectedly reduced incidence and
      severity of graft vs. host disease compared with allogeneic marrow infusion.

PMID- 9766443
TI  - CD34++ CD38- and CD34+ CD38+ human hematopoietic progenitors from fetal liver,
      cord blood, and adult bone marrow respond differently to hematopoietic cytokines
      depending on the ontogenic source.
AB  - CD34++ CD38- and CD34+ CD38+ hematopoietic progenitor cells (HPCs) from human
      fetal liver (FL), cord blood (CB), and adult bone marrow (ABM) were isolated and
      investigated for their growth characteristics, cytokine requirements and response
      to two modulators of early hematopoiesis, interferon (IFN)-gamma and macrophage
      inflammatory protein (MIP)-1alpha. We observed first that a significantly lower
      percentage of CD34++ cells were CD38- in ABM than in FL and CB. Second, the
      functional differences between CD34++ CD38- and CD34+ CD38+ cells were less
      pronounced in FL and CB than in their ABM counterparts. Third, an inverse
      correlation was found between growth factor response and the ontogenic age of
      HPCs, and a direct correlation was noted between cytokine requirements and the
      ontogenic age of HPCs. Fourth, spontaneous colony formation in a classic
      semisolid culture system was reproducibly obtained only in the ontogenically
      earliest cells, that is, in FL but not in CB and ABM, in which no such
      spontaneous colony formation was observed. Fifth, the modulatory effects of IFN
      gamma and MIP-1alpha were qualitatively different depending on the ontogenic age
      of the progenitor source: whereas IFN-gamma was only a selective inhibitor of
      primitive CD34++ CD38- ABM progenitor cells, it inhibited both CD34++ CD38- and
      CD34+ CD38+ FL and CB cells to the same extent. In contrast to the effects of MIP
      1alpha on ABM, we could not find any consistently stimulatory or inhibitory
      effects on FL and CB progenitors. In conclusion, important functional and
      biologic differences exist between FL, CB, and ABM progenitor cells, and these
      differences could have major implications for the use of these cell populations
      in preparative protocols of ex vivo expansion, transplantation strategies, or
      gene transfer experiments.

PMID- 9766444
TI  - p53-dependent and -independent differentiation of leukemic U-937 cells:
      relationship to cell cycle control.
AB  - Observations based on overexpression of the suppressor gene p53 or interference
      with endogenous p53 support a role for p53 in mediating not only growth
      inhibition and apoptosis but also differentiation. The aim of this study was to
      characterize the mechanisms of p53-dependent differentiation in the monoblastic
      leukemia cell line U-937. These cells were transfected with a mutant of the p53
      gene expressing wild-type p53 at a permissive temperature. The results showed
      that wild-type p53 and interferon (IFN)-gamma were able to work synergistically
      to promote differentiation. This cooperative response was not associated with
      early G1 arrest of the cell cycle, indicating that p53 can mediate
      differentiation by mechanisms other than those used for mediating G1 arrest. The
      differentiation response to transfected p53 with or without INF-gamma was
      inhibited by cyclic adenosine monophosphate (cAMP)-inducing agents (dibutyryl
      cyclic adenosine 3':5'-monophosphate, forskolin, and 3-isobutyl-1-methylxanthine)
      in a dose-dependent manner. In contrast, the differentiation response of p53
      negative U-937 cells to 1,25-dihydroxychole-calciferol or all-trans retinoic acid
      was enhanced by cAMP-inducing agents at optimal concentrations and inhibited at
      higher concentrations. In addition, 1,25-dihydroxycholecalciferol-mediated
      differentiation could be achieved in cells arrested in G1 by concomitant
      incubation with cAMP-inducing agents, indicating that differentiation can occur
      in the absence of proliferation. In conclusion, the results of this study
      indicate that p53-dependent and -independent differentiation can occur
      independently of cell cycle regulation.

PMID- 9766446
TI  - Immunophenotypic characterization of stromal cells in aspirated human bone marrow
      samples.
AB  - The presence of stromal cells was investigated in aspirated bone marrow prepared
      by the same method as that used for the initiation of human long-term bone marrow
      culture (hLTBMC). In previous studies, we performed immunocytochemical staining
      of cytocentrifuge cell preparations using a panel of antibodies with which we
      characterized stromal cell populations in hLTBMC. This approach allowed
      morphological as well as immunophenotypic assessment of cells of interest.
      Morphologically distinctive cell populations expressing vascular cell adhesion
      molecule-1 and low-affinity nerve growth factor receptor (NGFR) were observed to
      be present, but no cells expressing alpha-smooth muscle actin were found. Few
      macrophages were present, consistent with the origin of hLTBMC stroma-adherent
      macrophages from monocytes and their precursor cells rather than from mature
      macrophages among the culture-initiating cells. In the absence of double
      immunostaining, it was not possible to deduce whether CD34+ cells, which were
      present in varying numbers in the cytocentrifuge preparations, included stromal
      as well as primitive hematopoietic cells. In addition to single cells,
      multicellular tissue fragments containing a variety of stromal cell types were
      detected in many samples. Their presence raises the possibility that at least
      some components of hLTBMC stroma may arise by explant growth from complex tissue
      fragments containing vascular and fibroblastic elements. Overall, our results
      indicate that demonstration of a variety of stroma-associated antigens, in
      particular NGFR, provides a useful new tool for identifying stromal elements in
      aspirated bone marrow.

PMID- 9766445
TI  - Modulation of iron metabolism in monocytic THP-1 cells and cultured human
      monocytes by the acute-phase protein alpha1-antitrypsin.
AB  - The reticuloendothelial (RE) system plays an important role in the changes in
      iron metabolism associated with the anemia of chronic disease (ACD). We
      previously reported that the acute-phase protein alpha1-antitrypsin (alpha1-AT)
      reduced growth and proliferation in cells of the erythroid cell system by
      interfering with transferrin (Tf)-mediated iron uptake. The regulation of iron
      metabolism in cells of the RE system is distinctly different from that in other
      cell systems; moreover, monocytes and macrophages play an essential part in the
      regulation of the production and clearance of alpha1-AT. In the present study we
      examined the effect of alpha1-AT on cells of the monocyte-macrophage lineage.
      Alpha1-AT completely inhibited the binding of Tf to its receptor (TfR) on THP-1
      human myelomonocytic cells and cultured human monocytes. Results of equilibrium
      saturation and kinetic studies indicated that this inhibition was competitive. No
      other acute-phase protein demonstrated the same inhibitory potency. Furthermore,
      alpha1-AT almost completely prevented internalization of the Tf-TfR complex in a
      dose-dependent manner. Interestingly, and in sharp contrast to the results of our
      studies with erythroid cells, this inhibition did not reduce the growth and
      proliferation of THP-1 cells. Furthermore, alpha1-AT significantly increased the
      concentration of intracellular ferritin in THP-1 cells and monocytes, whereas the
      number of TfR remained unchanged. Because alpha1-AT showed no enhancing effect on
      ferritin transcription and translation, we believe that an as-yet unidentified
      posttranslational mechanism may be responsible for this phenomenon. In addition,
      our results indicate that the increase in ferritin concentration caused by alpha1
      AT is mediated independently of iron supply, as has previously been shown for
      several proinflammatory cytokines. These data provide further evidence that
      alpha1-AT is a mediator of the alterations in iron metabolism characteristic of
      ACD.

PMID- 9766447
TI  - Eradication of residual disease by administration of leukemia-specific T cells
      after experimental allogeneic bone marrow transplantation.
AB  - It is now well established that allogeneic lymphocytes can mediate a potent graft
      vs.-leukemia (GVL) reaction when administered to bone marrow transplant (BMT)
      recipients. The benefit of allogeneic lymphocyte transfusion is limited because
      many patients develop graft-vs.-host disease (GVHD) with prolonged pancytopenia,
      which sometimes proves fatal. The object of the present study was to determine
      the antileukemic potential and GVHD risk of in vivo-generated tumor-specific
      allogeneic T cells given shortly after BMT. BALB/C (H-2d) mice were inoculated
      with different cell doses (10(5) and 5 x 10(5)) of the A20 leukemia (BALB/C
      origin) 2 days prior to lethal total-body irradiation (TBI) and transplantation
      of allogeneic, major histocompatibility complex (MHC)-matched DBA marrow grafts
      (H-2d, minor difference to BALB/C). Donors of BM grafts and T cells were
      allogeneic, MHC-matched mice (DBA, H-2d, minor difference to BALB/C). Donor-type
      T cells were generated from mice immunized with irradiated A20 leukemia cells or
      nonmalignant BALB/C splenocytes and restimulated in vitro. Whereas no significant
      immunotherapeutic effect was seen in mice with high tumor burden (5 x 10(5)),
      allogeneic BMT in mice inoculated with 1 x 10(5) A20 cells resulted in a modest
      antileukemic effect. This survival rate remained unchanged when 10(6) T cells
      obtained from donors immunized with nonmalignant BALB/C derived cells were given
      posttransplantation. In contrast, a single injection of 10(6) T cells from
      leukemia-immunized donors led to potent GVL effects without mediating clinically
      overt GVHD. Our data provide evidence for the hypothesis that minimal residual
      disease can be eradicated without inducing GVHD by administering small amounts of
      specific allogeneic cytotoxic T cells after BMT.

PMID- 9766448
TI  - Lisinopril, an angiotensin I-converting enzyme inhibitor, prevents entry of
      murine hematopoietic stem cells into the cell cycle after irradiation in vivo.
AB  - The hemoregulatory peptide N-Acetyl-Ser-Asp-Lys-Pro (AcSDKP) has been shown in
      vivo to inhibit the cycling of murine hematopoietic stem cells triggered into S
      phase by either cytotoxic drug administration or irradiation. This property,
      further confirmed using in vitro models, demonstrates that the peptide has an in
      vivo protective effect on the hematopoietic system. AcSDKP has been shown to be a
      physiological substrate of angiotensin I-converting enzyme (ACE), which
      catabolizes the peptide through a dipeptidasic activity. Thus, oral
      administration of ACE inhibitor to humans has led to an increase in the plasma
      AcSDKP concentration. In the present paper, we report on the in vivo effect of
      lisinopril, an ACE inhibitor, on the proliferative status of murine hematopoietic
      stem cells triggered into S-phase by irradiation. Administration of lisinopril
      (10 mg/kg) 1 hour after irradiation led to a 90 to 100% inhibition of murine
      plasma ACE activity as observed during the first 4 hours postirradiation. This
      inhibition was correlated with a 600% increase in the endogenous plasma AcSDKP
      level and a total suppression at 24 hours of entry of the hematopoietic stem cell
      into the cell cycle. We discuss the possible role of ACE in the regulation of
      hematopoietic stem cell proliferation through control of the AcSDKP
      concentration.

PMID- 9766449
TI  - Macrophage-stimulating protein (MSP) and its receptor, RON, stimulate human
      osteoclast activity but not proliferation: effect of MSP distinct from that of
      hepatocyte growth factor.
AB  - Stem cell-derived tyrosine kinase (STK) is a member of the hepatocyte growth
      factor (HGF) receptor family. The ligand for STK, macrophage-stimulating protein
      (MSP), is a serum protein activated by members of the coagulation cascade. The
      RON gene is a human homolog of the murine STK. In this study we examined the role
      of MSP-RON in the signal pathway of human osteoclasts. Using anti-RON antibody,
      we detected RON expressed in multinucleated osteoclast-like cells (OCLs) formed
      in cultures of human bone marrow cells. To determine bone resorption, we placed
      OCLs on thin films of ceramic calcium phosphate formed on quartz plate-coated
      slides (Millenium Biologix) and measured pit formation. MSP stimulated pit
      formation by OCLs in a dose-dependent manner. MSP (50 ng/mL) caused a fourfold
      increase in pit area compared with the control. Furthermore, we examined the
      effects of MSP and HGF on OCL formation by purified populations of hematopoietic
      progenitors. OCLs were phenotypically identified by their cross-reactivity with
      23c6, a monoclonal antibody that preferentially binds to osteoclasts. HGF (50
      ng/mL) stimulated the differentiation of progenitors to 23c6-positive OCLs but
      did not enhance bone absorption. In contrast, MSP did not affect proliferation of
      osteoclast precursors but stimulated bone resorption by OCLs. We conclude that
      the MSP signal transduction pathway plays a role in bone resorption that is
      distinct from that of HGF.

PMID- 9766450
TI  - CD34 expression by embryonic hematopoietic and endothelial cells does not require
      c-Myb.
AB  - CD34 is a cell-surface glycoprotein expressed in a developmental, stage-specific
      manner by bone marrow stem and progenitor cells. In this study we explored a
      possible role for c-Myb in CD34 regulation during developmental hematopoiesis.
      The results indicate that c-Myb can induce CD34 expression in hematopoietic and
      nonhematopoietic cells, and that murine CD34 promoter activity is enhanced in
      myeloid cells transgenic for c-Myb. To test whether c-Myb is necessary for CD34
      expression during developmental hematopoiesis in vitro, c-Myb-null D3 embryonic
      stem (ES) cells were analyzed for their ability to develop CD34+ hematopoietic
      cells in vitro. CD34 promoter activity in transient transfections and CD34
      upregulation during ES cell differentiation into embryoid bodies was identical in
      wild-type and c-Myb-null ES cells, indicating that c-Myb is not required for CD34
      expression. CD34 protein is expressed on both hematopoietic and endothelial cells
      of the E8.5 blood islands during the development of c-Myb-null embryos, and
      expression is nearly identical in wild-type and c-Myb-null embryos. However, in
      E12.5 c-Myb-null embryos, the majority of identifiable CD34+ cells in the
      developing liver are endothelial rather than hematopoietic, which is consistent
      with the absence of colony-forming units in c-Myb-null embryos and developing ES
      cells. These data indicate that c-Myb is not required for CD34 expression in
      endothelial or primitive hematopoietic cells in the yolk sac, but is necessary
      for definitive hematopoiesis.

PMID- 9766451
TI  - Inhibition of interleukin-1beta-converting enzyme in human hematopoietic
      progenitor cells results in blockade of cytokine-mediated apoptosis and expansion
      of their proliferative potential.
AB  - Inhibitory and stimulatory cytokines regulate the function and survival of
      hematopoietic progenitor cells. Interactions between cytokines and progenitor
      cells may result in programmed cell death. Apoptosis of hematopoietic cells
      ultimately serves to diminish the size of the stem cell compartment in bone
      marrow (BM) failure, and this has frustrated efforts at ex vivo expansion of
      hematopoietic stem cells for BM transplantation. We previously demonstrated that
      triggering of the Fas-receptor, which is expressed on BM CD34+ cells, mediates
      apoptosis of progenitor cells. Although interleukin-1beta-converting enzyme (ICE)
      appears to be an important factor in the signaling cascade regulating Fas
      mediated apoptosis of lymphoid cells, its role in apoptosis of CD34+ cells has
      not been explored. In this study, we determined whether ICE protein was present
      in CD34+ cells and assessed its role in limiting expansion of hematopoietic stem
      cells by apoptosis. We demonstrated that ICE mRNA was constitutively produced in
      CD34+ cells, although the active form of ICE protein was not detected in fresh,
      unstimulated CD34+ cells from healthy donors. ICE protein could be induced in
      these CD34+ cells when they were cultured for 24 hours in the presence of
      hematopoietic growth factors. Interferon (IFN)-gamma and Fas agonist (CH11
      monoclonal antibody) enhanced ICE expression and triggered CD34+ cell apoptosis
      and cell death. In both short- and long-term BM cultures, hematopoietic colony
      forming cell numbers were increased after ICE blockade with a synthetic ICE
      inhibitor (Ac-Tyr-Val-Ala-Asp-aldehyde), even in the absence of IFN-gamma,
      suggesting that ICE regulates the proliferation and cell death of committed and
      primitive progenitor cells. The suppressive effect of IFN-gamma and Fas agonist
      on colony formation was also antagonized by ICE inhibitor. The effects of ICE
      blockade on proliferation of hematopoietic progenitors cells were related to
      inhibition of apoptosis, as demonstrated by annexin staining and in situ terminal
      dideoxytransferase apoptosis assays. Our results suggest that ICE protein is
      present in CD34+ cells after exposure to cytokines, that regulation of the levels
      of ICE protein in CD34+ cells is posttranscriptional, and that ICE plays a role
      in the regulation of apoptosis and expansion of primitive hematopoietic cells.
      ICE inhibition could potentially be used to reverse intrinsic and cytokine
      mediated apoptotic signals for the purpose of stem and progenitor cell expansion.

PMID- 9766452
TI  - About reference citations.

PMID- 9766453
TI  - Acknowledging sources in scholarly work.

PMID- 9766454
TI  - Predicting pressure ulcer risk: a multisite study of the predictive validity of
      the Braden Scale.
AB  - BACKGROUND: There have been no studies that have tested the Braden Scale for
      predictive validity and established cutoff points for assessing risk specific to
      different settings. OBJECTIVES: To evaluate the predictive validity of the Braden
      Scale in a variety of settings (tertiary care hospitals, Veterans Administration
      Medical Centers [VAMCs], and skilled nursing facilities [SNFs]). To determine the
      critical cutoff point for classifying risk in these settings and whether this
      cutoff point differs between settings. To determine the optimal timing for
      assessing risk across settings. METHOD: Randomly selected subjects (N= 843) older
      than 19 years of age from a variety of care settings who did not have pressure
      ulcers on admission were included. Subjects were 63% men, 79% Caucasian, and had
      a mean age of 63 (+/-16) years. Subjects were assessed for pressure ulcers using
      the Braden Scale every 48 to 72 hours for 1 to 4 weeks. The Braden Scale score
      and skin assessment were independently rated, and the data collectors were blind
      to the findings of the other measures. RESULTS: One hundred eight of 843 (12.8%)
      subjects developed pressure ulcers. The incidence was 8.5%, 7.4%, and 23.9% in
      tertiary care hospitals, VAMCs, and SNFs, respectively. Subjects who developed
      pressure ulcers were older and more likely to be female than those who did not
      develop ulcers. Braden Scale scores were significantly (p = .0001) lower in those
      who developed ulcers than in those who did not develop ulcers. Overall, the
      critical cutoff score for predicting risk was 18. Risk assessment on admission is
      highly predictive of pressure ulcer development in all settings but not as
      predictive as the assessment completed 48 to 72 hours after admission.
      CONCLUSIONS: Risk assessment on admission is important for timely planning of
      preventive strategies. Ongoing assessment in SNFs and VAMCs improves prediction
      and permits fine-tuning of the risk-based prevention protocols. In tertiary care
      the most accurate prediction occurs at 48 to 72 hours after admission and at this
      time the care plan can be refined.

PMID- 9766455
TI  - Self-report and polysomnographic measures of sleep in women with irritable bowel
      syndrome.
AB  - BACKGROUND: Women who report chronic gastrointestinal symptoms compatible with a
      diagnosis of irritable bowel syndrome (IBS) frequently report sleep disturbances.
      OBJECTIVES: The purposes of this study were to (a) compare self-reported and
      polysomnographic indicators of sleep quality in women with IBS symptoms (IBS-SX,
      n= 16) and controls (n= 16); (b) examine the relationship between the indicators
      of sleep quality; and (c) determine the relationship between sleep indicators and
      psychological distress. METHOD: The women slept in a laboratory for 2 consecutive
      nights. Polysomnographic measurements were recorded during sleep, and a sleep
      questionnaire was completed upon awakening each morning. Psychological distress
      was measured with the Symptom Checklist-90-R during the initial interview.
      RESULTS: Women in the IBS-SX group reported significantly greater numbers of
      awakenings during sleep (p = .008) and had a longer latency to REM sleep (p =
      .04) than did the controls. Self-reported and polysomnographic indicators were
      more highly correlated in the control group than in the IBS-SX group. In the IBS
      SX group, the greater the psychological distress, the less alert (rs = .419) and
      rested (rs = .564) the women felt in the morning and the more time the women
      spent in stages 3 and 4 sleep (rs = .479) and less in stage 2 (rs = -.447) and
      REM (rs = -.414) sleep. In the control group, psychological distress was not
      significantly associated with self-reported measures but was significantly
      associated with the number of awakenings (rs = .506) and time in stages 3 and 4
      sleep (rs = -.677). CONCLUSIONS: Although the women in the IBS-SX group reported
      significantly more awakenings, the weak relationship between self-reported and
      polysomnographic indicators suggests that clinicians must keep in mind that
      further assessments may be necessary.

PMID- 9766456
TI  - Differences in cortisol, a stress hormone, in women with turmoil-type
      premenstrual symptoms.
AB  - BACKGROUND: A significant number of American women of childbearing age are
      troubled by premenstrual symptoms, but the underlying cause is not understood,
      resulting in inadequate therapy. OBJECTIVES: To use basal levels of cortisol to
      differentiate women with low symptom (LS) patterns of turmoil-type premenstrual
      symptoms from women with premenstrual symptom (PMS) patterns and from women with
      premenstrual magnification (PMM) patterns of turmoil-type premenstrual symptoms.
      METHOD: Symptom and cortisol patterns of women were monitored for three
      consecutive menstrual cycles. Three distinct groups of women were identified
      based on symptom patterns and types. RESULTS: Significant differences in symptom
      severity among groups were observed during the follicular (F = 203; df= 2, 24; p
      < .0001) and luteal phases (F= 51.3; df= 2, 24; p< .0001) of the cycle. There
      were no statistically significant differences in cortisol among groups for the
      follicular phase, but there were during the luteal phase (F= 4.0; df= 2, 24; p=
      .03). CONCLUSIONS: Altered regulation of the stress axis may be involved in
      mediating turmoil-type PMS.

PMID- 9766457
TI  - A longitudinal causal model of cardiac invalidism following myocardial
      infarction.
AB  - BACKGROUND: Invalidism has been discussed in the cardiovascular literature for
      decades. Researchers have studied health perceptions, emotional distress, and
      dependency in patients after acute myocardial infarction in an attempt to
      understand the phenomenon. However, no theory of the manner in which these
      variables interact has been proposed. OBJECTIVES: Using previous research, a
      model of invalidism was specified in which individuals' perceptions that their
      health is poor lead to emotional distress and increased dependency. As health
      perceptions improve over time, emotional distress and dependency decrease.
      METHOD: Survey data were collected from 111 men and women 1 and 4 months after a
      first myocardial infarction and were tested using structural equation modeling.
      RESULTS: The model was rejected using a confirmatory approach (chi2(89) = 141.40;
      p= .00034). The fit indices, however, suggested an adequate fit of the model to
      the data (CFI = .96; NNFI = .94). CONCLUSION: The conclusion is that the model is
      reasonable and serves as a starting point for a theory-based empirical
      exploration of the invalidism process.

PMID- 9766459
TI  - The practical effects of errors in reference lists in nursing research journals.
AB  - BACKGROUND: Previous studies have noted the prevalence of errors in journal
      reference lists, including nursing journals, but an in-depth study of nursing
      research journals has not been repeated. OBJECTIVES: The purpose of this study
      was to determine the number and types of errors in nursing research journal
      reference lists. METHOD: A stratified random sample of 262 references from three
      nursing research journals was obtained. References were compared with the actual
      articles, books, and chapters cited, or with photocopies obtained via
      interlibrary loan. Error rates were calculated. RESULTS: The overall error rate
      was 45.8%; 38.3% of all references contained at least one major error, and 13.8%
      of all references contained at least one minor error. CONCLUSIONS: The overall
      rate of reference errors falls within the range exhibited by recent studies of
      the medical and dental literature but exceeds the rates found in studies of
      nursing journals and veterinary medicine journals. Researchers need to consider
      the number and types of errors involved when using reference lists in their
      research.

PMID- 9766458
TI  - Effect of positioning on SvO2 in the critically ill patient with a low ejection
      fraction.
AB  - BACKGROUND: Critically ill patients with a low ejection fraction may be
      vulnerable to decreased mixed venous oxygen saturation (SvO2) resulting from
      position change. OBJECTIVES: The objectives of this study were to describe the
      effects of changes in positioning on SvO2 in critically ill patients with a low
      ejection fraction (< or = 30%) and to describe the contribution of variables of
      oxygen delivery (DO2) and oxygen consumption (VO2) to the variance in SvO2.
      METHOD: An experimental two-group repeated-measures design was used to study 42
      critically ill patients with an ejection fraction of less than or equal to 30%
      (M= 19.5%). Patients were assigned randomly to one of two position sequences:
      supine, right lateral, left lateral; or supine, left lateral, right lateral. Data
      on SvO2 were collected at baseline, each minute after position change for 5
      minutes, and at 15 and 25 minutes. RESULTS: Repeated-measures multivariate
      analysis of variance showed a difference in SvO2 among the three positions across
      time (p< .0001), with the greatest differences occurring within the first 4
      minutes and in the left lateral position. Stepwise multiple regression showed
      that VO2 accounted for a greater proportion of the variance in SvO2 with position
      change than did DO2 (54% [p = .001] vs. 31% [p= .001]). CONCLUSIONS: Changes in
      SVO2 occur with positioning in critically ill patients with a low ejection
      fraction. These changes are transient and are the result of changes in VO2 rather
      than changes in DO2.

PMID- 9766461
TI  - Spirofungin, a new antifungal antibiotic from Streptomyces violaceusniger Tu
      4113.
AB  - A new secondary metabolite was detected in the culture filtrate and extracts of
      Streptomyces violaceusniger Tu 4113 by HPLC-diode-array and HPLC-electrospray
      mass-spectrometry screening. The compound named spirofungin has a polyketide
      spiroketal structure and shows various antifungal activities, particularly
      against yeasts.

PMID- 9766460
TI  - Demethyl mutactimycins, new anthracycline antibiotics from Nocardia and
      Streptomyces strains.
AB  - New anthracycline antibiotics 3'-O-demethyl mutactimycin (3) and 4-O,3'-O
      didemethyl mutactimycin (4) were isolated from two actinomycetes strains,
      Nocardia transvalensis and Streptomyces sp. GW 60/1571. The chemical structures
      were elucidated by mass spectrometry and NMR spectroscopy. Antibiotic 3 displayed
      moderate antimicrobial activity against Gram-positive bacteria and cytotoxicity
      against P388, L1210 and HeLa tumor cells (IC50; 9.6, >25 and 20 microg/ml,
      respectively).

PMID- 9766462
TI  - Hongoquercins, new antibacterial agents from the fungus LL-23G227: fermentation
      and biological activity.
AB  - Two new antibiotics, hongoquercins A and B, were isolated from fermentation
      extracts of the unidentified fungus LL-23G227. In the optimum medium, titers of
      the A and B components reached approximately 2.1 g/liter and 0.02 g/liter,
      respectively. The optimum temperature for antibiotic production was approximately
      22 degrees C. Growth was delayed at 15 degrees C but appeared to reach higher
      levels than was observed at 22 degrees C. Addition of dextrose to growth media
      increased hongoquercin B production. Hongoquercin A exhibited moderate activity
      against Gram-positive bacteria. Mechanistic studies conducted in an E. coli imp
      strain suggested membrane damage as the primary mode of bactericidal action.
      These compounds also lysed human red blood cells, suggesting a similar mode of
      action on eukaryotic cells.

PMID- 9766463
TI  - MJ347-81F4 A & B, novel antibiotics from Amycolatopsis sp.: taxonomic
      characteristics, fermentation, and antimicrobial activity.
AB  - Strain MJ347-81F4 has been found to produce two new cyclic thiazolyl peptide
      antibiotics, components A and B. Taxonomic studies including morphological and
      physiological characteristics and chemical analysis of whole cells of the
      producing strain revealed this microorganism to belong to genus Amycolatopsis,
      and so we designated the strain Amycolatopsis sp. MJ347-81F4. After 10 to 12 days
      of fermentation, most of the antibacterial activity was present mainly in the
      mycelial cake and reached its maximum level. In comparison with reference
      compounds, A as the major component showed excellent in vitro activity against
      gram-positive bacteria including highly methicillin-resistant Staphylococcus
      aureus (MRSA) and Enterococcus faecalis with MICs in the range of concentration
      of 0.006 to to approximately 0.1 microg/ml. The results on the antimicrobial
      activity against thiazolyl peptide-resistant mutants of Bacillus subtilis NRRL B
      558 indicated that the possible molecular target of MJ347-81F4 component A might
      be the 50S subunits of the ribosome, the inactivation of which would inhibit
      protein synthesis.

PMID- 9766465
TI  - The novel enzymatic 3''-N-acetylation of arbekacin by an aminoglycoside 3-N
      acetyltransferase of Streptomyces origin and the resulting activity.
AB  - Kanamycin group antibiotics were subjected to enzymatic acetylation by a cell
      free extract containing an aminoglycoside 3-N-acetyltransferase, AAC(3)-X,
      derived from Streptomyces griseus SS-1198PR. Characterization of the incubated
      reaction mixtures by TLC and antibiotic assay revealed that a product retaining
      activity was specifically formed from arbekacin, an anti-MRSA semisynthetic
      aminoglycoside. The structural determination demonstrated that acetylation
      occurred at the 3"-amino group in arbekacin and amikacin, and at the 3-amino
      group in dibekacin as in the case of kanamycin. These results should reflected
      the effect of the (S)-4-amino-2-hydroxybutyryl side chain which is present in
      arbekacin and amikacin, but absent in dibekacin and kanamycin. The 3"-N
      acetylation is the first finding in the enzymatic modifications of aminoglycoside
      antibiotics. 3"-N-Acetylarbekacin showed antibiotic activity as high as that of
      2'-N-acetylarbekacin reported previously, whereas 3"-N-acetylamikacin showed no
      substantial activity. Thus, our results illuminated a novel aspect of arbekacin
      distinct from the other aminoglycosides.

PMID- 9766464
TI  - Discovery of MC-02,331, a new cephalosporin exhibiting potent activity against
      methicillin-resistant Staphylococcus aureus.
AB  - A systematic approach toward building activity against methicillin-resistant
      staphylococci into the cephalosporin class of beta-lactam antibiotics is
      described. Initial work focused on finding the optimal linkage between the cephem
      nucleus and a biphenyl pharmacophore, which established that a thio linkage
      afforded potent activity in vitro. Efforts to optimize this activity by altering
      substitution on the pharmacophore afforded iodophenylthio analog MC-02,002, which
      although highly potent against MRSA, was also highly bound to serum proteins.
      Further work to decrease serum protein binding showed that replacement of the
      iodo substituent by the positively-charged isothiouronium group afforded potent
      activity and reduced serum binding, but insufficient aqueous solubility.
      Solubility was enhanced by incorporation of a second positively-charged group
      into the 7-acyl substituent. Such derivatives (MC-02,171 and MC-02,306) lacked
      sufficient stability to staphylococcal beta-lactamase enzymes. The second
      positive charge was incorporated into the cephem 3-substituent in order to
      utilize the beta-lactamase-stable aminothiazolyl(oximino)acetyl class of 7
      substituents. These efforts culminated with the discovery of
      bis(isothiouroniummethyl)phenylthio analog MC-02,331, whose profile is acceptable
      with respect to potency against MRSA, serum binding, aqueous solubility, and beta
      lactamase stability.

PMID- 9766467
TI  - Antibiotic activities and affinities for bacterial cell wall analogue of N
      demethylvancomycin and its derivatives.
AB  - N-Demethylvancomycin, which has been clinically used in China, is one member of
      vancomycin group (glycopeptide) antibiotics. It differs from vancomycin only in
      that methyl group on the amino group of the N-terminal residue of vancomycin has
      been replaced by H. By reductive alkylation of N-demethylvancomycin, we
      synthesized N-alkyl and N,N'-dialkyl N-demethylvancomycins, which closely
      correlated with vancomycin in structure. The association constants of the
      complexes of N-demethylvancomycin and its analogues with di-N-Ac-L-Lys-D-Ala-D
      Ala and the antibiotic activity against Staphylococcus aureus of the
      glycopeptides were determined. Results showed that N-demethylvancomycin has
      higher affinity for bacterial cell wall analogue di-N-Ac-L-Lys-D-Ala-D-Ala and
      more potent antibiotic activity against Staphylococcus aureus than vancomycin.
      Both N-alkylation and N,N'-dialkylation of N-demethylvancomycin reduced the
      affinity and antibiotic activity. The longer the alkyl groups, the less potent
      antibiotic activities and lower affinities have the glycopeptides. The antibiotic
      activities against Staphylococcus aureus of N-demethylvancomycin and its
      analogues roughly parallel their affinities for di-N-Ac-L-Lys-D-Ala-D-Ala.

PMID- 9766466
TI  - Efficacy of syringomycin E in a murine model of vaginal candidiasis.
AB  - Syringomycin E (SR-E), a new antifungal produced by the bacterium Pseudomonas
      syringae pv. syringae, was evaluated in a murine vaginal candidiasis model. In
      one study, mice were treated intravaginally b.i.d. for 4 days with drug carrier,
      SR-E 2% in either PEG-400 or PEG-ointment, or 1% clotrimazole as a positive
      control. Quantitative vaginal cultures were taken prior to treatment on day 1 and
      on days 5, 6, and 7. Both formulations showed a reduction of yeast colonization
      in the vaginas on day 5 (P< or =0.06 and P< or =0.03 for SR-E/PEG-400 and SR
      E/PEG ointment, respectively) and SR-E/PEG ointment reduced the colonization on
      day 7 (P< or =0.06) when compared to carrier treated controls. In a second study,
      SR-E was formulated in Aquaphor at three higher concentrations of SR-E [3%, 6%,
      or 12% (w/v)]. SR-E showed dose-dependent efficacy. The 3% dose showed no effect
      while the 6% and 12% doses reduced the number of yeasts. The 12% dose showed a
      significant reduction on days 5 (P< or =0.01), 6 (P< or =0.06), and 7 (P< or
      =0.03) when compared with the drug carrier controls and on day 5 was more
      effective than clotrimazole (P< or =0.03). Clotrimazole did not significantly
      reduce the yeasts in the vagina until days 6 (P< or =0.01) and 7 (P< or =0.01)
      when compared to the drug carrier controls. No vaginal inflammatory response was
      evident by histological examination in uninfected animals treated with SR-E. No
      SR-E could be detected in plasma, kidney, or liver. SR-E (12%) was an effective
      treatment when compared to 1% clotrimazole.

PMID- 9766468
TI  - Synthesis and structure-activity relationships of 1beta-methylcarbapenems with
      quaternary ammonium side chains.
AB  - The synthesis and antibacterial activity of 1beta-methylcarbapenems with
      quaternary ammonium groups at the C-2 position have been studied. Two types of
      new carbapenem derivatives have been synthesized. These 1beta-methylcarbapenems,
      one type having a (2S,4S)-2-[1,1-dimethyl-2-(1-piperazinyl)carbonyl]pyrrolidinio
      4-+ ++ylthio group and the other type having a (2S,4S)-2-(4-carbamoylmethyl-4
      methylhomopiperazinio-1-yl carbonyl)pyrrolidin-4-ylthio group, show potent and
      well balanced antibacterial activity as well as high stability against
      dehydropeptidase-I. The in vivo potency of these two carbapenems was compared
      with that of meropenem. The structure-activity relationships leading to these
      carbapenems are also described.

PMID- 9766469
TI  - Cladinose analogues of sixteen-membered macrolide antibiotics. VI. Synthesis of
      metabolically programmed, highly potent analogues of sixteen-membered macrolide
      antibiotics.
AB  - Five novel 3-hydroxyl derivatives of sixteen-membered macrolide possessing 4-O
      acyl-alpha-L-cladinose as a neutral sugar moiety were synthesized by using a
      combination of structurally stable silyl acetal protection and selective
      hydrogenolysis of a 3"-methylthiomethyl ether to a 3"-OMe group. Several
      derivatives having n-butyryl, i-butyryl and n-valeryl substituent at the 4"-OH
      group exhibited significant antibacterial activity in vitro. One of them, 4"-O-n
      butyryl-3"-O-methylleucomycin V, showed improved therapeutic effect in mice.

PMID- 9766470
TI  - Synthesis and in vitro antibacterial activity of catechol-spiramycin conjugates.
AB  - The first synthesis of siderophore conjugates of two macrolide antibiotics,
      spiramycin 1 and neospiramycin 2, which are unable to penetrate the outer
      membrane of gram-negative bacteria are described. These novel conjugates were
      prepared by regioselective acylation of a hydroxyl function of 1 and 2 with a
      dihydroxybenzoic Fe(III) complexing ligand linked via a carboxyl group containing
      spacer to the macrolide antibiotics. The preliminary biological evaluation of
      these novel conjugates under standard and iron depleted conditions has shown that
      their antibacterial activity was comparable to that of spiramycin 1 and
      neospiramycin 2.

PMID- 9766471
TI  - Conversion of spinosyn A and spinosyn D to their respective 9- and 17
      pseudoaglycones and their aglycones.
AB  - Forosamine at the 17-position of spinosyns A and D was hydrolyzed under mild
      acidic conditions to give the corresponding 17-pseudoaglycones. The tri-O
      methylrhamnose at the 9-position of the 17-pseudoaglycone of spinosyn A was
      hydrolyzed under more vigorous acidic conditions to give the aglycone of spinosyn
      A. However, these conditions led to decomposition of the 17-pseudoaglycone of
      spinosyn D, presumably due to more facile protonation of the 5,6-double bond to
      produce a tertiary carbonium ion which undergoes further rearrangements.
      Spinosyns J and L (3'-O-demethyl spinosyn A and D, respectively) obtained from
      fermentation of biosynthetically-blocked mutant strains of Saccharopolyspora
      spinosa, were oxidized to give the corresponding 3'-keto-derivatives and the
      resultant keto-sugars were then beta-eliminated under basic conditions to give
      the 9-pseudoaglycones of spinosyns A and D respectively. Forosamine at the 17
      position of the 9-pseudoaglycone of spinosyn D was then readily hydrolyzed to
      yield the aglycone of spinosyn D.

PMID- 9766472
TI  - Effects of tryprostatin derivatives on microtubule assembly in vitro and in situ.

PMID- 9766473
TI  - The aluminum reclamation industry work environment: are unidentified neurotoxins
      present?

PMID- 9766474
TI  - Does work in the aluminum reclamation industry cause neurobehavioral
      abnormalities?

PMID- 9766475
TI  - Relationship between acute ozone responsiveness and chronic loss of lung function
      in residents of a high-ozone community.
AB  - We hypothesized that acute respiratory responsiveness to ozone predicts chronic
      lung injury from repeated exposure to ozone-containing air pollution. We tested
      this hypothesis in 164 middle-aged nonsmoking residents of an ozone-polluted
      community who underwent lung-function measurements during 1986 and 1987 (i.e.,
      time 3). The time-3 study was a follow up of more comprehensive studies conducted
      in 1977-1978 (time 1) and in 1982-1983 (time 2). In contrast to the apparent
      rapid (i.e., approximately 60 ml/y) decline in lung-function measurements between
      times 1 and 2, our subjects showed little change in forced vital capacity (FVC)
      or forced expired volume in 1 s (FEV1.0) between times 2 and 3, and they
      experienced a normal decline between times 1 and 3. A subgroup (n = 45) underwent
      2-h laboratory ozone exposures to 0.4 ppm ozone, accompanied by intermittent
      exercise, and they experienced mild acute reductions in FEV1.0 and FVC, but there
      was little change in bronchial responsiveness to methacholine. Individual acute
      responses to laboratory ozone were not correlated with individual long-term
      changes between times 1 and 3. In summary, the results did not support our
      initial hypothesis, and they did not confirm rapid function decline in nonsmokers
      chronically exposed to ozone-containing air pollution.

PMID- 9766476
TI  - Short-term effects of low-level winter pollution on respiratory health of
      asthmatic adults.
AB  - We studied the short-term effects of Paris winter air pollution (i.e., sulfur
      dioxide, Black Smoke, suspended particulates with an aerodynamic diameter close
      to 10 microm, and nitrogen dioxide) in 40 nonsmoking mild to moderate asthmatics
      (52% male; mean age = 46 y; 90% treated with inhaled steroids). During a 6-mo
      period, subjects recorded asthma symptoms and three daily peak expiratory flow
      measurements. Statistical analysis (i.e., generalized estimating equation models
      that accounted for autocorrelation of responses, weather data, and time trends)
      revealed consistent and significant associations between the pollutants and
      asthma attacks and symptoms in the entire study group, especially in the subgroup
      of individuals who took inhaled beta2 agonists as needed. Pollutants correlated
      negatively with morning peak expiratory flow in the subgroup that took inhaled
      beta2 agonists as needed, and they correlated positively with daily variability
      in asthmatics who received regularly scheduled inhaled beta2 agonists. The
      effects lingered several days after exposure occurred. Low-level pollution has
      consistent measurable effects on nonsmoking adults who have well-treated mild or
      moderate asthma.

PMID- 9766477
TI  - Neurobehavioral impairment and symptoms associated with aluminum remelting.
AB  - The author's objective was to assess whether aluminum reclamation (recycling)
      exposure in a plant in the southeastern United States was associated with
      neurobehavioral and pulmonary impairment and symptoms. The author made cross
      sectional comparisons of 41 workers to 32 local and 66 regional referents to
      assess whether aluminum recycling was associated with neurobehavioral and
      pulmonary impairment and symptoms. Methods included neurophysiological,
      psychological, and pulmonary-function tests; a Profile of Mood States (POMS); and
      questionnaires. The exposed subjects had slower simple and choice reaction times
      than referents (i.e., 77 milliseconds [ms] versus 137 ms, respectively [p <
      .0001]); balance in the exposed subjects, measured as sway speed (with eyes
      closed), was .32 cm/s faster than for referents (p < .005); and color
      discrimination was less acute in exposed subjects (p < .0001). In the exposed
      versus referent subjects, Culture Fair scores were lower by a factor of 8.3 (p <
      .0001), Trail Making A was 10 s longer (p < .001), Trail Making B was 50 s longer
      (p < .0001), peg placement required an additional 9 s (p < .008), and POMS scores
      were fourfold higher (p < .0001). These described differences were not explained
      by age, bias, or confounding factors. Workers had more neurobehavioral,
      rheumatic, and respiratory symptoms than did referents. The author attributed the
      differences between the two groups to chemical exposures from aluminum remelting,
      including aluminum, manganese, vinyl chloride monomer, and other chemicals.
      Workplace air could not be sampled, but because a problem was identified, levels
      of these, as well as other chemicals, should be measured in future studies.

PMID- 9766478
TI  - Cancer incidence and risks in selected agricultural settlements in the Negev of
      Israel.
AB  - Medical staff of two Negev kibbutzim invited epidemiologists to help them
      investigate cancer rates among their members. Our objectives were (a) to
      determine whether the cancer rate in the kibbutzim was elevated or abnormal and
      (b) to determine the role of agricultural and other relevant exposures if cancer
      incidence was elevated. We validated cases of cancer by kibbutz records and by
      surveying other information; we computed expected values on the basis of the age
      sex-calendar period and site-specific cancer incidence rates reported by the
      Israel Cancer Registry for the entire population; and we compared the data for
      the 2 kibbutzim with data derived for similar age and sex groups in 2 other
      kibbutzim, which were assumed not to have increased cancer rates. In addition, we
      planned and conducted a case-referent study, including the design, pretest, and
      use of questionnaires, including data about lifetime exposures (i.e., type of
      work and its duration, agricultural and industrial chemicals, smoking and alcohol
      use, demographic variables, health experiences, and family history). In only one
      of the kibbutzim, for which high cancer rates were suspected, was there
      significant excess for all sites in persons who were less than 40 y of age. In
      one of the "comparison" kibbutzim, we found increased cancer rates overall. Much
      of the excess in the high cancer kibbutzim was in hematological cancer (i.e.,
      leukemia and lymphoma). Multiple years of work in fields, orchards, and
      landscape, as well as orchard work that commenced before 1960, were associated
      with increased risk of cancer (p < .08). We also found an association between
      cancer rate and numbers of industrial chemicals used (p < .08). Pipe and
      cigarette smoking were also associated with increased cancer incidence. In the
      multivariate analysis, the association with calendar year in which orchard work
      was started and multiple exposures to industrial chemicals was stronger than
      associations noted in the univariate analyses. Although duration of agricultural
      work or multiple industrial exposures were clearly associated with increase in
      cancer risk, we were unable to identify the causal role of specific agent(s).
      Nonetheless, educational programs for cancer prevention can be based, in part, on
      the results of such a study.

PMID- 9766479
TI  - Children exposed to chronic contamination after the Chernobyl accident:
      cytogenetic and radiotoxicological analyses.
AB  - In this study, we describe cytogenetic studies of lymphocytes obtained from
      children who were exposed after the Chernobyl accident to low doses of ionizing
      radiation. We sought to determine possible chromosomal damage relative to
      internal contamination, as measured by whole-body counter and urine
      radiotoxicological analyses. The study was performed during a 1-mo period on the
      peripheral blood of children hosted in Italy, but who resided in contaminated
      regions of the Russian Federation and Belarus. We used conventional cytogenetics
      to detect chromosomal aberrations. In some cases, we also used "chromosome
      painting" to look for stable aberrations. There were more acentric fragments in
      subjects than in controls; a few chromosome and chromatid breaks werefound in the
      subjects, but this finding did not differ significantly between subjects and
      controls.

PMID- 9766481
TI  - Reactive Intestinal Dysfunction Syndrome (RIDS) caused by chemical exposures.
AB  - In this study, the authors describe a new "reactive syndrome," Reactive
      Intestinal Dysfunction Syndrome (RIDS), which has similarities to the previously
      described clinical syndromes Reactive Airway Dysfunction Syndrome (RADS) and
      Reactive Upper Airway Dysfunction Syndrome (RUDS). Given that at least 5
      neuropeptides are common to both the respiratory tract and digestive tract, the
      authors propose that the abnormal secretion of these neuropeptides or the
      abnormal numbers of their receptors play a role in what is perceived clinically
      as RADS, RUDS, and RIDS. The relatively large surface areas of both the lungs and
      gut render them especially vulnerable to the environment to which they are
      exposed constantly.

PMID- 9766480
TI  - Increased cardiopulmonary disease risk in a community-based sample with chemical
      odor intolerance: implications for women's health and health-care utilization.
AB  - Chemical intolerance, or reported illness from odors of common environmental
      chemicals (e.g., car exhaust, pesticides), is emerging as an important
      environmental and public health-care issue. Epidemiologic methods provide
      relevant heuristic devices for studies of complex disorders, such as chemical
      intolerance. The authors examined personal and reported parental cardiopulmonary
      disease prevalence rates in a community sample of chemically intolerant and
      control individuals. A county government (Tucson, Arizona) employee and kin
      subset (N = 181; 113 households) completed standard health questionnaires.
      Investigators determined chemical intolerance (n = 41/181) from self-reports of
      individuals who felt "moderately" to "severely" ill from exposure to at least
      three of five chemicals (i.e., car exhaust, pesticides, paint, new carpet, and
      perfume) on a Chemical Odor Intolerance Index. The authors chose the control
      group (n = 57/181) on the basis of self-reports of "never" feeling ill on the
      Chemical Odor Intolerance Index. The chemically intolerant group, which primarily
      comprised women (78% versus 51% of controls, p < .05), was significantly more
      likely to report-and to have sought--medical attention for heart problems,
      bronchitis, asthma, and pneumonia. Reports of heart problems in the chemically
      intolerant index cases and the occurrence of heart disease in both of their
      parents were significant (Fisher's p < .05). The chemically intolerant
      individuals were also significantly more likely to report maternal histories of
      chest problems (e.g., inhalant allergens, tuberculosis) than controls. The
      findings of the study suggested that the chemically intolerant individuals (a
      preponderance of whom were women [sex-related risk]) were more likely to have (a)
      reported cardiopulmonary problems (i.e., greater health risk); (b) actively
      sought medical care for these problems (i.e., increased medical utilization); and
      (c) reported more parental illnesses-particularly heart disease, asthma, and
      diabetes (i.e., genetic risk). Additional community-based studies of chemical
      intolerance are needed.

PMID- 9766482
TI  - Exposure to power frequency magnetic fields and risk of breast cancer in the
      Upper Cape Cod Cancer Incidence Study.
AB  - Investigators used a population-based case-control study to evaluate the
      relationship between breast cancer risk and exposure to 60-Hz magnetic fields
      from various sources. There was no increase in breast cancer risk associated with
      (a) holding a job with high (odds ratio [OR] = 1.2; 95% confidence interval [CI]
      = 0.4, 3.4) or medium (OR = 0.9; 95% CI = 0.5, 1.7) exposure to magnetic fields;
      (b) living in a home heated electrically (OR = 1.0; 95% CI = 0.7, 1.4); or (c)
      sleeping with an electric blanket (OR = 1.0; 95% CI = 0.7, 1.4). There was a
      nonsignificant 50% increase in risk for subjects who lived within 152 m (500 ft)
      of an electricity transmission line or substation (OR = 1.5; 95% CI = 0.6, 3.3).
      Although limited by small numbers and exposure misclassification, the data in
      this study did not support the hypothesis that exposure to 60-Hz magnetic fields
      increases the risk of breast cancer in women.

PMID- 9766483
TI  - The histopathology of ankylosing spondylitis: are there unifying hypotheses?
AB  - This article examines some fundamental features of the histopathology of
      ankylosing spondylitis (AS) such as inflammation in the entheses and
      syndesmophyte formation. This may be linked to the generation of transforming
      growth factor in inflammation, which can stimulate bone formation, and to the
      molecular composition of entheses where molecules are present, such as the
      proteoglycan aggrecan, that are normally found in cartilage. Immunity to these
      molecules is observed in patients with AS and in experimental immunity to
      aggrecan, or the G1 domain only, which can cause spondylitis. Involvement of
      other tissues (the eye and arterial vessels) may be due to crossreactive
      immunity.

PMID- 9766484
TI  - Clinical aspects of the spondyloarthropathies.
AB  - The spondyloarthropathies are a group of inflammatory arthritic conditions
      characterized by the absence of rheumatoid factor, and the presence of
      spondylitis, sacroiliitis, and an asymmetric peripheral arthritis. Familial
      aggregation and the presence of enthesitis, skin and mucous membrane lesions,
      bowel complaints, eye involvement, and aortic root dilatation are also features
      of these conditions. An association with HLA-B27 has been documented in the
      diseases constituting the spondyloarthropathies, including ankylosing
      spondylitis, Reiter's disease/reactive arthritis, psoriatic arthritis, and the
      arthritis of inflammatory bowel disease. Although there are similarities among
      the entities included in this group, each of these conditions have specific
      characteristics that help distinguish them. Differences in response to
      medications and in prognosis are such that it is important to make the correct
      diagnosis in the individual patient.

PMID- 9766485
TI  - HLA-B27 and the seronegative spondyloarthropathies.
AB  - In the 25 years since the initial reports of the association of HLA-B27 with
      ankylosing spondylitis (AS) and subsequently with Reiter's syndrome, psoriatic
      spondylitis, and the spondylitis of inflammatory bowel disease, the association
      of HLA-B27 with the seronegative spondyloarthropathies has remained one of the
      best examples of a disease association with a hereditary marker. HLA-B27 has been
      recognized as representative of a spectrum of diseases, ranging from the majority
      of HLA-B27-positive individuals who have no disease at all, through those with
      isolated eye or skin involvement, to those with critical eye, heart, and
      peripheral joint compromise of full-blown AS. Yet HLA polymorphism has evolved in
      response to environmental stresses, and even the presence of HLA-B27 itself
      appears to confer advantages in certain infectious diseases, such as acquired
      immune deficiency syndrome (AIDS). This article will review what is currently
      known about HLA-B27 and disease, especially in the seronegative
      spondyloarthropathies. The structure-function relationship of HLA-B27 will be
      presented, including differences between the B27 subtypes both in their ethnic
      variation and possible disease implications. The disease spectrum conferred by
      the presence of HLA-B27 will also be discussed, and the theories of how HLA-B27
      contributes to the pathogenesis of the spondyloarthropathies will be considered.

PMID- 9766486
TI  - Arthritis in HLA-B27 transgenic animals.
AB  - This review focuses on investigations of rats and mice transgenic for HLA-B27;
      these animals have been investigated for several years as potential models for
      the human spondyloarthropathies. Spontaneous multisystem disease occurs in rats
      with high expression of B27 and human beta2-microglobulin (hbeta2m). The disease
      is T-cell-dependent and is sensitive to both environmental and genetic
      manipulation. A spontaneous arthritis and enthesopathy has been observed by some
      investigators in nontransgenic mice which seems to be more prevalent in B27
      transgenic mice. Peripheral arthritis has also been reported in B27 transgenic
      mice that lack mouse beta2m. Potential insights from these animals into the
      pathogenesis of B27-related disease are discussed.

PMID- 9766487
TI  - The pathogenesis of HLA-B27 arthritis: role of HLA-B27 in bacterial defense.
AB  - The way in which a host accommodates invasive facultative intracellular bacteria
      must be the key to the development of reactive arthritis. Investigators have
      analyzed the bacterial events at several levels: invasion into host cells,
      intracellular survival, translocation from the sites of infection to the joints,
      residence in the joints, and evasion of host defense. Because HLA-B27 is present
      in higher incidence in patients with reactive arthritis and is an essential gene
      in the related ankylosing spondylitis, the role of HLA-B27 in host defense is
      also assumed to be important in the development of reactive arthritis. This
      review summarizes the various studies in this field.

PMID- 9766488
TI  - Infectious agents as triggers of reactive arthritis.
AB  - Reactive arthritis was originally defined as a sterile joint inflammation after
      infection elsewhere in the body, but this view has been challenged in the past
      decade since different antigens and DNA and RNA of various triggering microbes
      have been shown to exist at the sites of inflammation in the joints. It has been
      suggested that microbial antigens, or intact pathogens, are important for the
      pathogenesis of reactive arthritis, at least in the early phase of the disease,
      but the exact mechanism of how the pathogens contribute to the development of
      this usually self-limiting polyarthritis has not been discovered. This article
      reviews the theories on the role of infectious agents as triggers of reactive
      arthritis.

PMID- 9766489
TI  - Insights into the pathogenesis of psoriasis and psoriatic arthritis.
AB  - Psoriasis and its related arthritis are chronic inflammatory disorders affecting
      predominantly the skin and synovium. Although their etiology remains to be
      established, multiple factors seem to play important roles in their pathogenesis.
      These environmental (eg, infectious agents and trauma), genetic, and immunologic
      factors are reviewed in this article.

PMID- 9766490
TI  - A multicenter study of the prevalence and susceptibility patterns of isolates of
      Streptococcus pneumoniae with reduced susceptibility to penicillin G in
      Louisiana.
AB  - Because of increasing reports of multiple-antibiotic-resistant strains of
      Streptococcus pneumoniae and associated clinical failures, this study was
      performed to determine the prevalence of multiresistance among strains from nine
      Louisiana medical centers. Using a National Committee for Laboratory Standards
      broth microdilution method, 481 strains were tested. Of these, 70% were
      penicillin-susceptible (PS), 23% had intermediate minimum inhibitory
      concentration values to penicillin (I), and 7% were fully resistant to penicillin
      (PR). The isolation rates (15% to 40% for I strains and 0% to 33% for PR strains)
      at the various medical centers varied appreciably. The prevalence of penicillin
      resistance was highest among upper respiratory isolates, while cross-resistance
      to other antimicrobials varied. The least cross-resistance was noted among PS
      strains. However, strains with reduced penicillin susceptibility had high levels
      of cross-resistance. Among I strains, the prevalence of cross-resistance (%) was
      noted for amoxicillin/clavulanate (6%), cefuroxime (71%), cefaclor (91%),
      ceftriaxone (13%), cefotaxime (34%), erythromycin (67%), azithromycin (32%), and
      clarithromycin (32%). For PR strains, the prevalence of cross-resistance was 97%
      for amoxicillin/clavulanate, cefuroxime, and cefaclor; 67% for ceftriaxone and
      erythromycin; 89% for cefotaxime; and 69% for azithromycin and clarithromycin.
      These data emphasize the high prevalence of multiple-antimicrobial-resistance
      among strains of S pneumoniae with reduced penicillin susceptibility in this
      geographic area.

PMID- 9766491
TI  - Esophageal papillomatosis from human papilloma virus proven by polymerase chain
      reaction.
AB  - Human papilloma viruses (HPVs) are known to infect the genitourinary tract, the
      skin, the anal canal, and the upper respiratory tract. Esophageal papillomas and
      especially HPV-induced squamous papillomas of the esophagus are rare. The authors
      report a case of extensive HPV-induced esophageal polyposis, which was probably
      sexually transmitted. The 53-year-old female patient presented with chronic
      diarrhea and had occult blood in the stool. She underwent
      esophagogastroduodenoscopy, at which time multiple esophageal polyps were
      observed and biopsy specimens obtained. Histologic evaluation was consistent with
      benign papillomas. Polymerase chain reaction and DNA hybridization of the
      biopsied tissue specimens confirmed the diagnosis of HPV infection. Because of
      our observation and because of HPV's relationship to cervical and esophageal
      cancer, further evaluation of HPV as the cause of esophageal papillomatosis and
      as a risk factor for esophageal cancer is warranted.

PMID- 9766492
TI  - Lymphoma cell lines: in vitro models for the study of HHV-8+ primary effusion
      lymphomas (body cavity-based lymphomas).
AB  - Primary effusion lymphoma (PEL; also known as body cavity-based lymphoma) is
      recognized as a new and unique lymphoma entity occurring predominantly, but not
      exclusively in human immunodeficiency virus (HIV)-seropositive patients with
      acquired immunodeficiency syndrome (AIDS). PEL grows exclusively in body cavities
      as serous lymphomatous effusion without evidence of mass disease or
      dissemination. Their most unique feature is infection with the newly discovered
      human herpesvirus-8 (HHV-8; also known as Kaposi's sarcoma-associated
      herpesvirus), often accompanied by co-infection with Epstein-Barr virus (EBV). A
      number of continuous lymphoma cell lines have been established from the malignant
      pleural effusion, ascitic fluid and peripheral blood of patients with AIDS- and
      non-AIDS-associated PEL. While all cell lines are HHV-8+, about half of them also
      contain EBV sequences. Stimulation of the cell lines causes switch from latent to
      lytic HHV-8 infection. The cells are generally negative for T and B cell
      immunomarkers (except for CD138 suggesting a pre- or terminal plasma cell stage)
      and positive for some activation and adhesion markers; they are genotypically B
      cells with their immunoglobulin genes rearranged. Complex, hyperdiploid
      karyotypes with multiple structural abnormalities are seen in the cell lines
      examined. No alterations of known proto-oncogenes are detected in PEL, with the
      exception of BCL-6 mutations occurring in a large percentage of cases.
      Heterotransplantation of the cell lines into immunodeficient mice leads to the
      development of lymphomatous effusion and marked angiogenesis. As HHV-8 contains
      DNA sequences of several protein homologues, the cell lines express various
      cytokines, cytokine receptors, chemokines, cell cycle and anti-apoptosis
      modulators which are upregulated upon stimulation. Indeed, some cell lines
      produce high levels of (human) interleukin-6 and interleukin-10. Taken together,
      these cell lines represent very important model systems for the elucidation of
      the pathobiology of PEL; furthermore, the cell lines are extremely useful
      scientific tools providing a resource to pursue studies of HHV-8-mediated
      pathogenic mechanisms.

PMID- 9766493
TI  - Clinical study of 9-cis retinoic acid (LGD1057) in acute promyelocytic leukemia.
AB  - The use of all-trans retinoic acid (RA) for remission induction markedly
      increases survival of patients with acute promyelocytic leukemia (APL) compared
      to patients treated solely with cytotoxic chemotherapy. However, clinical
      resistance to this agent develops rapidly, which has been associated with a
      progressive decline in plasma drug concentrations. Previous studies suggested
      that 9-cis RA, a retinoid receptor 'pan agonist' did not induce its own
      catabolism to the same extent as all-trans RA. Therefore, we conducted a dose
      ranging study of this compound in patients with both relapsed and newly diagnosed
      APL. We treated 18 patients with morphologically diagnosed APL (13 relapsed, five
      newly diagnosed). The daily dose of 9-cis RA ranged from 30 to 230 mg/m2/day
      given as a single oral dose. Four of 12 (33%) relapsed patients (three of whom
      were previously treated with all-trans RA) and four of five (80%) newly diagnosed
      patients achieved complete remission. The sole failure in the newly diagnosed
      group died early from an intracranial hemorrhage. One other patient with t(9;12)
      translocation had substantial hematologic improvement. The drug was generally
      well tolerated; headache and dry skin were the most common adverse reactions.
      Three patients were treated with corticosteroids for signs of incipient 'RA
      syndrome.' These preliminary data suggest that 9-cis RA is an effective agent for
      remission induction and deserves further investigation in patients with retinoid
      sensitive APL.

PMID- 9766494
TI  - Combination of aclarubicin and etoposide for the treatment of advanced acute
      myeloid leukemia: results of a prospective multicenter phase II trial. German AML
      Cooperative Group.
AB  - In order to develop new strategies for the treatment of relapsed or refractory
      acute myeloid leukemia, the German AML Cooperative Group performed a prospective
      multicenter phase II study to evaluate the antileukemic efficacy of aclarubicin
      60 mg/m2/day and etoposide 100 mg/m2/day each given for 5 days. Of 37 heavily
      pretreated evaluable patients (median age 42 years, range 18-81) 15 (40%)
      achieved a remission after one or two courses of treatment consisting of nine
      complete (24%) and six partial remissions (16%). Fourteen (38%) cases were non
      responders and eight (22%) patients suffered from early deaths. Disease-free
      survival for patients in remission and overall survival were 3.2 months each. The
      median duration of critical neutropenia <500/microl was 27 days. The most
      frequent non-hematologic side-effects were stomatitis (WHO III/IV, 48%),
      infections (40%), nausea/vomiting (26%) and diarrhea (24%). Cardiac toxicity was
      mild. This study suggests a substantial antileukemic efficacy and an acceptable
      toxicity of aclarubicin in combination with etoposide in heavily pretreated
      patients with advanced acute myeloid leukemia, and warrants further evaluations
      in a more favorable stage of the disease.

PMID- 9766495
TI  - Anti-asparaginase antibodies following E. coli asparaginase therapy in pediatric
      acute lymphoblastic leukemia.
AB  - Asparaginase is an effective antileukemic agent and is included in most front
      line protocols for pediatric acute lymphoblastic leukemia (ALL) worldwide;
      however, allergic reactions to asparaginase may be dose-limiting. We evaluated
      plasma anti-asparaginase antibody concentrations in a cohort of children with
      newly diagnosed ALL, who did and who did not exhibit clinical hypersensitivity,
      after Escherichia coli (E. coli) asparaginase therapy. Thirty-five children who
      received asparaginase 10000 IU/m2 i.m. three times weekly for nine doses as part
      of both multiagent induction and reinduction chemotherapy, and seven monthly
      doses during the first 7 months of continuation treatment, were studied. Twenty
      two patients experienced initial allergic reactions to asparaginase during
      continuation (n=20) or reinduction (n=2) phases and 13 children did not exhibit
      any reaction. An enzyme-linked immunosorbent assay (ELISA) was used to measure
      anti-asparaginase antibodies in plasma samples, diluted 1:3200, using E. coli
      asparaginase as the antigen. The median anti-asparaginase antibody concentration
      (OD at 1:3200 dilution) increased from 0.039 at induction to 0.506 at reinduction
      in patients who exhibited clinical hypersensitivity (P = 0.0002). By comparison,
      median antibody level increased from 0.011 to 0.032 OD at identical time points
      in patients who did not react to asparaginase (P = 0.02). Both post-induction and
      post-reinduction anti-asparaginase antibody levels were higher in reacting than
      in nonreacting patients (P = 0.004 and P = 0.01, respectively). Antibody levels
      were inversely related to the time elapsed between the reaction and sampling (P =
      0.011). Although anti-asparaginase antibody levels increased from the post
      induction plasma sample to the post-reinduction sample in 28 of 35 patients
      regardless of whether they exhibited clinical hypersensitivity, patients with
      hypersensitivity reactions had higher antibody levels than did identically
      treated control patients at comparable time points in therapy. Therefore,
      antibody analysis may be of clinical value in predicting future hypersensitivity.

PMID- 9766497
TI  - Characterization of H+-ATPase-dependent activity of multidrug resistance
      associated protein in homoharringtonine-resistant human leukemic K562 cells.
AB  - Multidrug resistance (MDR), caused by overexpression of either P-glycoprotein or
      the multidrug resistance-associated protein (MRP), is characterized by a
      decreased cellular drug accumulation due to an enhanced drug efflux. Many studies
      on cells overexpressing MRP and/or Pgp, have shown a concentration of the drug
      inside cytoplasmic acidic vesicles followed by an exocytotic process. In this
      study, we examined the effects of 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole or NBD
      (a H+-ATPase pump inhibitor), buthionine sulphoximine or BSO (an inhibitor of
      glutathione (GSH) biosynthesis) and verapamil or VPL (a calcium channel blocker)
      on the subcellular distribution of daunorubicin or DNR in K562 cells
      overexpressing MRP (K-H30) and Pgp (K-H300) and A549 cells overexpressing
      spontaneously MRP. Nucleo-cytoplasmic distribution of DNR was carried out using
      scanning confocal microspectrofluorometry. This technique allows determination of
      nuclear accumulation of anthracyclines. Our results show that nuclear
      accumulation of DNR in K-H30 and A549 cells was increased by NBD, BSO and VPL
      while in K-H300 cells, only VPL was able to increase nuclear accumulation of DNR.
      Similarly, NBD, BSO and VPL could reverse DNR resistance in K-H30 cells whereas,
      in K-H300 cells, only VPL increased the sensitivity of these cells. These data
      suggest a requirement for GSH in MRP-mediated resistance and suggest that even if
      vesicular sequestration can happen in cells overexpressing MRP and Pgp proteins,
      probably only the MRP protein is able to extrude the drug through intracellular
      vesicles and efflux. Finally, NBD and BSO might be a useful agents in
      facilitating discrimination between Pgp and MRP phenotypes and prognosis in
      patients.

PMID- 9766496
TI  - Duration of first remission predicts remission rates and long-term survival in
      children with relapsed acute myelogenous leukemia.
AB  - Although treatment of childhood acute myelogenous leukemia (AML) has
      substantially improved in the last 15 years, in nearly half of the patients
      disease recurs. The aim of this study was to establish the prognosis of relapsed
      childhood AML and to identify prognostic factors for achievement of second
      remission and survival. From February 1988 to July 1996, 134 children with first
      relapse of AML were reported to the study center of the AML-BFM group. 102
      patients treated intensively to induce second remission were prospectively
      followed. With various regimens, complete remission was achieved in 52 of 102
      patients (51%), 27 children were alive in median 2.5 years (range, 0.4-7 years)
      after relapse. Disease-free survival was observed in seven of 16 patients
      transplanted from a matched sibling donor, one of four after matched unrelated
      bone marrow transplantation, 10 of 22 after autologous transplantation and five
      of nine patients after chemotherapy alone (two patients were lost to follow-up).
      Time until relapse reflecting the duration of first remission is the only
      variable correlating CR and survival rates. Defining early relapse as less than
      1.5 years from diagnosis to relapse resulted in a 5-year survival of 10%, s.e. 5%
      for early relapses and 40%, s.e. 10% for late relapses (P-logrank test, 0.0001).
      Duration of first remission is a strong predictor for achievement of second CR
      and survival. It should be considered in reporting results of experimental
      therapies.

PMID- 9766498
TI  - Antileukemic action of buthionine sulfoximine: evidence for an intrinsic death
      mechanism based on oxidative stress.
AB  - The glutathione-depleting agent buthionine sulfoximine (BSO) was found to be
      toxic to some AML blast populations. This toxicity was manifested as the
      appearance of high levels of reactive oxygen generation in GSH-depleted cells,
      and later by the loss of mitochondrial membrane potential and an increase in
      intracellular calcium. Striking heterogeneity in BSO sensitivity was observed in
      a series of four human AML cell lines, and in fresh leukemic blasts obtained from
      eight AML patients. In some cases, toxicity was seen at BSO concentrations as low
      as 1 microM; approximately 100-fold less than the plasma levels achieved in
      patients treated with BSO as a drug resistance reversing agent. Based on these
      results we propose that some AML blast populations are unusually dependent on GSH
      based antioxidant mechanisms, due to high intrinsic rates of reactive oxygen
      generation. The mitochondrial respiratory chain is the most likely source of this
      reactive oxygen. Because toxicity is seen at clinically achievable concentrations
      of BSO, this agent might have antileukemic activity in patients.

PMID- 9766499
TI  - Processing/activation of caspases, -3 and -7 and -8 but not caspase-2, in the
      induction of apoptosis in B-chronic lymphocytic leukemia cells.
AB  - Chlorambucil and prednisolone, two commonly used drugs in the treatment of
      chronic lymphocytic leukemia (CLL), induce apoptosis in CLL cells. We have
      investigated the involvement in this apoptotic cell death of caspases, which
      cleave critical cellular substrates thereby acting as the executioners of the
      apoptotic process. Induction of spontaneous or chlorambucil/prednisolone-induced
      apoptosis of freshly isolated B-CLL cells in culture resulted in the activation
      of the 'effector' caspases, -3 and -7, but generally not of caspase-2. Activation
      of caspases-3 and -7 was accompanied by the proteolysis of the DNA repair enzyme,
      poly (ADP-ribose) polymerase. Induction of apoptosis was also accompanied by the
      processing of caspase-8, the extent of which varied between patients. Induction
      of apoptosis and processing of all the caspases was inhibited by the cell
      permeable caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethyl
      ketone (Z-VAD.fmk). Our results demonstrate a key role for the activation and
      processing of caspases in the execution phase of apoptosis in CLL cells.
      Apoptosis of CLL cells resulted in the selective activation of some but not all
      caspases. Our results suggest that the dysregulation of apoptosis observed in CLL
      may be due to the signalling leading to the activation of caspases rather than a
      deletion of pro-caspases. High levels of caspase-8 in CLL cells in conjunction
      with low levels of CD95 receptor may offer new therapeutic opportunities for the
      treatment of CLL.

PMID- 9766500
TI  - Resistance of t(4;11) (MLL-AF4 fusion gene) leukemias to stress-induced cell
      death: possible mechanism for extensive extramedullary accumulation of cells and
      poor prognosis.
AB  - Acute leukemias of the t(4;11) (MLL-AF4 fusion gene) type frequently have high
      white blood counts and extramedullary disease in multiple organs. In the present
      study we evaluated the hypotheses that this extensive disease is the result of
      extramedullary survival of leukemia cells due to resistance to stress-induced
      cell death. Leukemias with t(4;11)(MLL-AF4) were found to be resistant to the
      cell death that results from serum deprivation in vitro when compared with B
      lineage acute leukemias without t(4;11)(MLL-AF4). Cells with t(4;11)(MLL-AF4) did
      not have increased doubling time or increased numbers of cells in cycle. These
      results suggest that the alteration in cellular homeostasis in these leukemias is
      due to abnormalities of cellular destruction rather than cellular proliferation
      when compared to other leukemias. Our results are consistent with the hypothesis
      that death of non-t(4;11) leukemias occurs in the microenvironment outside of the
      bone marrow as a result of deficient cellular and humoral growth factors.
      Resistance to death signals in t(4;11) leukemias results in extensive
      accumulation of leukemia cells in extramedullary sites and likely contributes to
      the poor prognosis of these leukemias.

PMID- 9766501
TI  - Induction of sensitivity to NK-mediated cytotoxicity by TNF-alpha treatment:
      possible role of ICAM-3 and CD44.
AB  - SR-91 is a natural killer (NK)-resistant leukemic cell line expressing a low
      level of ICAM-1. Pre-treatment of SR-91 cells with TNF-alpha or IFN-gamma,
      increased both ICAM-1 (CD54) expression on SR-91 cells and binding to the human
      NK cell line NK-92. However, only TNF-alpha-treated SR-91 cells became sensitive
      to killing by NK-92 cells. The increased binding induced by both cytokines and
      the TNF-alpha-induced sensitivity of SR-91 cells to NK-92 cell killing were
      abrogated by anti-LFA-1 mAb as well as by a combination of antibodies against the
      three ligands of LFA-1 (CD11a/CD18), ICAM-1 (CD54), ICAM-2 (CD102) and ICAM-3
      (CD50). This indicated that LFA-1 interaction with the three ICAMs on SR-91 cells
      is essential for effector-target cell binding (which is a prerequisite for
      subsequent target cell lysis), but is insufficient to render the SR-91 cells
      sensitive to killing by NK-92 cells. TNF-alpha, but not IFN-gamma also induced
      the activation of LFA-1, CD44 and beta1 integrins on SR-91 cells. Based on these
      observations we propose that the differential effect of TNF-alpha and IFN-gamma
      could be related to the activation of certain adhesion molecules on the surface
      of SR-91 cells by TNF-alpha that, upon interaction with their counter-receptors
      on NK-92 cells, lead to the activation of the NK-92 cells.

PMID- 9766502
TI  - CD57+/CD28- T cells in untreated hemato-oncological patients are expanded and
      display a Th1-type cytokine secretion profile, ex vivo cytolytic activity and
      enhanced tendency to apoptosis.
AB  - Three-color flow cytometry immunophenotyping revealed significant increases of
      CD57+ and CD28- cells among both circulating CD4+ and CD8+ T lymphocytes of
      untreated hemato-oncological patients (n = 54) as compared to healthy donors (n =
      55), with CD57 and CD28 expression on the patients' T cells being largely
      reciprocal. Marked expansion of CD57+ cells among circulating CD4+ T lymphocytes
      was frequently detected in patients with chronic leukemia of B cell origin (B
      CLL, hairy cell leukemia) but not in patients with chronic myeloid leukemia,
      suggesting a causal relation with the tumor's major histocompatibility complex
      class II expression. Using immunomagnetic separation techniques, we further
      demonstrate that the patients' CD57+/CD28- T cells display a typical Th1-type
      cytokine secretion profile upon anti-CD3 stimulation, with a markedly higher
      secretion of the Th1-type cytokines IL-2, IFN-gamma, and TNF-alpha than their
      CD57-/CD28+ counterparts. Cytotoxic activity of circulating CD8+ T lymphocytes,
      measured ex vivo in an anti-CD3-redirected assay, was almost exclusively exerted
      by the CD57+/CD28- subset. Moreover, a marked cytotoxic activity was detected
      within CD4+CD57+ T cells from some B-CLL patients. Finally, the patients'
      CD57+/CD28- T cells displayed an increased tendency to apoptosis in culture.
      Collectively, our results indicate that the expanded CD57+/CD28- T cells in
      hemato-oncological patients represent differentiated effector cells, similar to
      their (quantitatively minor) counterpart in healthy donors. The reason for their
      expansion and their pathophysiologic significance, however, remains unclear.

PMID- 9766503
TI  - A cell surface molecule, JL1; a specific target for diagnosis and treatment of
      leukemias.
AB  - We previously reported a novel differentiation antigen, which is specifically
      expressed in stage II double positive (CD4+CD8+) human cortical thymocytes (Park
      et al, J Exp Med 1993; 178: 1447-1451). This study was designed to investigate
      the expression pattern of JL1 in various types of leukemic cells from patients
      and normal hematopoietic cells to evaluate the possibility as a tool for
      diagnosis and treatment of leukemia. The expression of JL1 antigen was observed
      in 75.6% of leukemic cases (117 out of 154 leukemic patients tested) on flow
      cytometric analysis. The percentage of JL1-positive cases of T lineage acute
      lymphoblastic leukemia (T-ALL) (92.6%) was higher than that of other types of
      leukemias (75%). The presence of JL1 antigen was also confirmed by immunoblotting
      and immunoprecipitation. Since the JL1 antigen is selectively expressed on the
      surface of human leukemic cells but not on the mature human peripheral blood
      cells, normal bone marrow cells and various types of normal tissues, JL1 could be
      an excellent candidate for an immunodiagnostic and immunotherapeutic tool for
      hematopoietic malignancies such as leukemia.

PMID- 9766504
TI  - Malignant myeloid transformation with isochromosome 7q in Shwachman-Diamond
      syndrome.
AB  - Shwachman-Diamond syndrome is an autosomal recessive disorder characterized by
      exocrine pancreatic dysfunction, bony metaphyseal dysostosis, various degrees of
      cytopenia, and a striking tendency to develop myelodysplastic syndrome and acute
      myeloblastic leukemia. Isochromosome 7 [i(7q)] is a rare non-random cytogenetic
      abnormality of myeloid cells in hematological malignancy. We report two cases of
      Shwachman-Diamond syndrome in which patients developed myelodysplastic syndrome
      and i(7q), detected by G-banding karyotype analysis and fluorescence in situ
      hybridization. Three other children have been previously reported to have
      myelodysplastic syndrome in association with i(7q); two of them had Shwachman
      Diamond syndrome. Isochromosome 7q may be a fairly specific marker of myeloid
      malignant transformation in this syndrome and play a role in its pathogenesis.

PMID- 9766505
TI  - Amifostine stimulates formation of multipotent and erythroid bone marrow
      progenitors.
AB  - Amifostine (WR-2721, Ethyol) is a phosphorylated aminothiol that affords broad
      cytoprotection from the myelosuppressive effects of antineoplastics. To further
      characterize its hematopoietic activities, we investigated the effects of
      amifostine and its dephosphorylated metabolite, WR1065, on the in vitro growth of
      human bone marrow progenitors. Preincubation exposure to amifostine or WR1065
      stimulated the growth of colony-forming units granulocyte, erythroid, macrophage,
      megakaryocyte (CFU-GEMM) and erythroid bursts (BFU-E) from bone marrow
      mononuclear cells in a dose-dependent fashion. Over the concentration range
      tested (0.1-1000 microM), pretreatment with the aminothiols enhanced formation of
      CFU-GEMM up to five-fold and BFU-E nine-fold, compared to a three-fold increase
      in myeloid colony recovery. In CD34+ selected cells, preincubation with
      amifostine increased formation of CFU-GEMM up to 38-fold and produced macroscopic
      colonies, exceeding colony number in cultures initiated with optimal
      concentrations of interleukin-1 (IL-1), IL-3, or kit ligand (KL). When compared
      with recombinant human cytokines, amifostine enhanced IL-1 and IL-3 induced
      colony formation, although its stimulatory effect was less than additive. In
      contrast, pretreatment with amifostine antagonized the stimulatory effects of KL,
      whereas synergy was observed with concurrent exposure. Ex vivo expansion studies
      showed that amifostine alone supported and augmented the production of myeloid
      progenitors in secondary cultures. Similarly, under cytokine-deficient
      conditions, amifostine promoted cell survival and delayed apoptosis as measured
      by nucleosome generation. These data indicate that amifostine is a novel
      multipotent hematopoietic stimulant that augments the formation and survival of
      bone marrow progenitors.

PMID- 9766507
TI  - Epidemiology and ethnic aspects of B cell chronic lymphocytic leukemia in Israel.
AB  - Chronic lymphocytic leukemia (CLL) represents 30% of all leukemias in Caucasians.
      In East Europe and USA the disease incidence is high while in Asia and Africa CLL
      is rare. The present study deals with 302 cases of B cell CLL and related
      disorders; 207 patients originating from Europe and America (Ashkenazi Jews) and
      95 descendants from Asia, The Mediterranean or Africa (Sephardic Jews). The
      patients were recruited during 1975-1996 in a single center covering the Hashfela
      region -- a Southern area of Israel with a current population of 430000
      inhabitants. Incidence of the disease, clinical pattern, biological parameters,
      prognosis and outcome were investigated and compared in both ethnic groups. The
      results of this study show a high incidence of CLL in Israel. The mean annual age
      adjusted incidence 4.3 per 100000 person-year is among the highest reported
      values. Our study confirms previous data on the prevalence of CLL in Ashkenazi
      compared to Sephardic Jews. The rise in CLL rate in the reviewed period occurred
      in both populations, mainly in the Sephardic group. The relative risk for
      Ashkenazies compared to Sephardics decreased from 6.0 in the 1975-1979 period to
      2.4 in 1990-1996. A high rate of CLL was found in new immigrants from the former
      USSR with 26 cases de novo diagnosed and 11 prevalent cases not included in this
      series among approximately 60000 new immigrants in the ara over the last 8 years.
      No differences were found in clinical, laboratory and immunological parameters at
      the time of diagnosis in the two ethnic groups. The follow-up showed a similar
      pattern in the disease evolution. A preliminary study of immunoglobulin heavy
      chain rearrangement performed in 14 patients showed no significant differences in
      JH hybridization in the early stages of the disease, but more aberrations in
      advanced CLL in the Ashkenazi group. Our findings suggest that ethnic origin of
      the patients itself does not affect the biological and clinical behavior of this
      disease.

PMID- 9766506
TI  - Effects of thrombopoietin, interleukin-3 and the kinase inhibitor K-252a on
      growth and polyploidization of the megakaryocytic cell line M-07e.
AB  - Thrombopoietin (TPO) is a recently cloned growth and differentiation factor
      implicated in megakaryocytopoiesis. Here, we show that TPO, interleukin-3 (IL-3)
      and, at least in short-term assays, also interferon gamma (IFN gamma) induced
      proliferation in acute myeloid leukemia (AML-M7)-derived M-07e cells. The Janus
      kinase/signal transducer and activator of transcription (JAK/STAT) pathway was
      activated after stimulation with any of the three cytokines. Thus, the TPO
      receptor (TPO-R) MPL was tyrosine phosphorylated after a short-term stimulation
      with TPO, followed by tyrosine phosphorylation of STAT 3 and STAT 5, but not of
      STAT 1. IL-3 and IFN gamma induced phosphorylation of STAT 5 or STAT 1,
      respectively, without affecting the other STATs. As STATs are thought to regulate
      proliferation by modulating expression of inhibitors of cyclin-dependent kinases
      (Cdk), we analyzed p21 and p27 expression after stimulation with TPO or IL-3. In
      contrast to the constitutively low p21 expression, p27 mRNA levels were high in
      synchronized, cytokine-deprived cells in G0/1 phase. Stimulation with TPO or IL-3
      induced a rapid decrease of p27 mRNA. The phosphorylation cycle of the
      retinoblastoma protein (Rb) was inversely correlated with the level of p27 mRNA.
      Hyperphosphorylation of Rb was detectable 9 h after onset of stimulation,
      concomitantly with the decrease of p27 mRNA and shortly before transition of the
      cells into S phase. As phosphorylation of Rb is a key event for transition of
      cells into S phase, our observations support the notion of p27 being an important
      regulator during cytokine-induced proliferation. Whether the JAK/STAT pathway is
      directly involved in p27 expression or not, remains to be elucidated. The JAK
      inhibitor AG-490 blocked cytokine-induced STAT 5 phosphorylation and
      proliferation of M-07e cells in a dose-dependent manner. Although these data
      indicate a role for the JAK/STAT pathway in cytokine-induced proliferation, a
      direct influence on the p27 mRNA downregulation has to be confirmed. The second
      major effect of TPO, polypoidization, could not be observed in M-07e cells. Even
      long-term culture with TPO did not induce endomitosis in these cells. However,
      polyploidization could be brought about by the kinase inhibitor K-252a. After 3
      days of exposure to this reagent, 17% of the originally mononucleated cells
      contained two to five nuclei. K-252a-induced polykaryon formation was not
      preceded by STAT 5 phosphorylation. Thus, K-252a did not mimic TPO stimulation at
      the early steps of the signaling chain. Taken together, our experiments confirm a
      role for the JAK/STAT pathway in cytokine-induced proliferation; TPO and IL-3
      induce downregulation of the Cdk inhibitor p27, hyperphosphorylation of Rb and
      subsequently transition of the cells into S phase; the kinase inhibitor K-252a
      induces polyploidization of M-07e cells, but this effect is independent of STAT 5
      phosphorylation.

PMID- 9766509
TI  - Decreasing antibiotic resistance of Enterobacteriaceae by introducing a new
      antibiotic combination therapy for neutropenic fever patients.
AB  - Prompt empiric antibiotic therapy is of critical importance for patients with
      neutropenic fever. However, a major concern with important clinical consequences
      is the emergence of bacterial resistance to antibiotics. After using ceftazidime
      with a glycopeptide as initial empiric therapy for neutropenic fever, we were
      confronted with a 75% reduced susceptibility rate to ceftazidime of inducible
      Enterobacteriaceae collected in 1994. The initial empiric therapy was therefore
      replaced in May 1995 by a combination of cefepime with amikacin, with addition of
      a glycopeptide after 48 h if necessary. After this change, we observed a
      significant decrease in reduced susceptibility of inducible Enterobacteriaceae,
      not only to ceftazidime, but also to amikacin, cotrimoxazole and ciprofloxacin.
      There was also a decrease in reduced susceptibility of non-inducible
      Enterobacteriaceae, such as Klebsiella spp, to ceftazidime. The reduction of
      resistance may be related at least in part to the combined use of cefepime
      together with an aminoglycoside. This study shows that it is possible to reverse
      bacterial resistance by modifying the antibiotic regimen used.

PMID- 9766508
TI  - Oral cytarabine ocfosfate in acute myeloid leukemia and non-Hodgkin's lymphoma-
      phase I/II studies and pharmacokinetics.
AB  - Cytosine arabinoside (AraC) is rapidly inactivated via systemic deamination with
      half-lives ranging from 1 h (i.v.) to 4 h (s.c.) -- and cannot be applied orally
      due to its hydrophilic properties. These limitations might be overcome by YNK01 -
      a lipophilic prodrug of AraC -- that is resistant to deoxycytidine deaminase and
      can be applied orally. In the present study the therapeutic activity, side
      effects and pharmacokinetics of YNK01 were evaluated in a phase I/II study
      including patients with relapsed or refractory acute myeloid leukemia (AML)
      (n=23) or low-grade non-Hodgkin's lymphoma (NHL) (n=20). YNK01 was given by 14
      day cycles with escalating doses starting with a daily dose of 50 mg/m2
      (equivalent to 20 mg/m2 AraC on a molar basis). The maximum tolerated dose was
      reached at the 600 mg/m2 dose level with WHO grade 3-4 diarrhoea as the main
      toxicity. In the 23 patients with AML two complete remissions, four partial
      remissions and three patients with stable disease were observed. In the 23
      patients with AML two complete remissions, four partial remissions and three
      patients with NHL two cases reached partial remission and six other patients
      mainained stable disease. Pharmacokinetic evaluations were performed during 34
      treatment cycles in 28 patients. The data suggest that YNK01 was absorbed in the
      distal part of the small intestine and taken up into hepatocytes. After hepatic
      psi and subsequent beta-oxydation of YNK01 the released AraC (and its deamination
      product AraU) appeared in the systemic circulation. Time of maximum concentration
      (h), half-life (h) and area under the curve (ng x h/ml, at the 1200 mg dose
      level) were as follows (VC variation coefficient) YNK01: 1.0 (0.58), 10.1 (0.43),
      12622 (0.65); AraC: 23.2 (0.57), 22.6 (0.36), 3496 (0.76); AraU: 19.2 (0.58) 22.3
      (0.33) 15441 (0.66). Of the total dose of YNK01 15.8% was absorbed and
      metabolized to AraC and AraU, defining the metabolic bioavailability of this
      prodrug. A linear relationship was observed between YNK01 dose and YNK01 AUC and
      AraC AUC over the whole dose range tested. AraC was released from hepatocytes
      over a prolonged period of time resulting in long lasting plasma levels similar
      to a continuous i.v. infusion. After administration of YNK01 at a dosage of 100
      150 mg/m2 plasma levels of AraC were comparable to those achieved after low-dose
      AraC treatment (20 mg/m2) while at doses of YNK01 of 450-600 mg/m2 concentrations
      of standard-dose AraC (100 mg/m2) were obtained. We conclude that YNK01 shows
      considerable activity against relapsed and refractory AML and NHL and that its
      pharmacokinetic properties offers advantages in comparison to (standard) i.v. or
      s.c. AraC in clinical practice.

PMID- 9766510
TI  - Structure of Bcl-1 and IgH-CDR3 rearrangements as clonal markers in mantle cell
      lymphomas.
AB  - Mantle cell lymphoma represent a clinicopathologically distinct entity of
      malignant non-Hodgkin's lymphoma (NHL) and are characterized by a specific
      chromosomal translocation t(11;14)(q13;q32) involving the cyclin D1 gene also
      designated as bcl-1/PRAD1 gene on chromosome 11 and the heavy chain
      immunoglobulin joining region on chromosome 14. We have established a PCR method
      to amplify t(11;14) junctional sequences in DNA from fresh frozen and paraffin
      embedded tissue by bcl-1-specific primers in combination with a consensus
      immunoglobulin JH primer. A total of 65 cases histologically classified as mantle
      cell lymphoma (MCL) were analyzed for the presence of a t(11;14) translocation
      and monoclonal IgH-CDR3 rearrangements. From 26 patients with classical MCL and
      three cases with the anaplastic variant of MCL fresh frozen biopsy material was
      available for DNA extraction. We detected a bcl-1/JH rearrangement in 12 out of
      29 samples (41%). In 36 cases paraffin-embedded lymph node tissue was the only
      source of DNA. In this material we found a bcl-1/JH rearrangement in six out of
      31 samples with intact DNA (20%). To confirm the specificity of the PCR and to
      determine the bcl-1/JH junctional region sequences as clone-specific marker in
      individual patients we characterized the junctional DNA sequences by direct PCR
      sequencing in 16 cases. Interestingly we found that six bcl-1/JH junctions
      harbored DH segments in their N regions indicating that bcl-1/JH rearrangements
      can occur in a later stage of B cell ontogeny during which the complete VH to DH
      JH joining or VH-replacement takes place. To investigate the suitability of IgH
      CDR3 as sensitive molecular marker for those MCL patients in which a t(11;14)
      translocation can not easily be amplified, we additionally analysed 60 cases for
      the presence of monoclonally rearranged IgH genes by IgH-CDR3-PCR. A monoclonal
      IgH-CDR3 PCR product could be identified in 24 out of 29 fresh frozen samples
      (79%) whereas only 11 out of 31 samples (36%) with paraffin-derived DNA were
      positive. We demonstrate that automated fluorescence detection of monoclonal IgH
      CDR3 PCR products allows the rapid and sensitive monitoring of minimal residual
      disease also in cases that lack a PCR amplifiable t(11;14) translocation. In
      combination with allele-specific primers the procedure may improve current
      experimental approaches for detection of occult MCL cells at initial staging and
      residual disease during and after therapy.

PMID- 9766511
TI  - Comparative genomic hybridization in childhood acute lymphoblastic leukemia.
AB  - DNA copy number changes were studied by comparative genomic hybridization (CGH)
      on bone marrow samples obtained from 72 patients with childhood acute
      lymphoblastic leukemia (ALL) at diagnosis. The patients had been admitted to the
      Helsinki University Central Hospital (Finland) between 1982 and 1997. CGH showed
      DNA copy number changes in 45 patients (62.5%) with a mean of 4.6 aberrations per
      patient (range, 1 to 22). The results of CGH and chromosome banding analysis were
      generally concordant, but CGH facilitated specific karyotyping in 34 cases. DNA
      copy number gains were more frequent than losses (gains:losses, 6:1). Gains of
      DNA sequences affected almost exclusively whole chromosomes and were most
      commonly observed in chromosomes 21 (25%), 18 (22.2%), X (19.4%), 10 (19.4%) and
      17 (19.4%). The most common partial gain was 1q31-q32 (8.3%). The most common
      gains of chromosomes 21, 18, X, 10, 17, 14, 4, 6 and 8 appeared concurrently.
      High-level amplifications of small chromosome regions were sporadic, detected
      only in two patients (2.8%). Chromosome 21 was involved in both cases. The most
      common losses were 9p22-pter (12.5%) and 12p13-pter (11.1%). No statistically
      significant association between the CGH findings and the diagnostic white blood
      cell count was observed.

PMID- 9766512
TI  - A novel single cell PCR assay: detection of human T lymphotropic virus type I DNA
      in lymphocytes of patients with adult T cell leukemia.
AB  - The abnormal lymphocytes in adult T cell leukemia (ATL) reveal a peculiar
      morphology that is characterized by indented or lobulated nuclei. While human T
      lymphotropic virus type I (HTLV-I) is thought to be integrated in ATL cells, the
      correlation between the nuclear irregularities and HTLV-I infection is obscure.
      We have devised a novel single cell polymerase chain reaction (PCR) technique to
      examine the integration of HTLV-I provirus genome in cells from two patients with
      ATL. To isolate single cells, peripheral blood smears were prepared on thin
      polyester slides and stained with May-Grunwald-Giemsa. Morphologically defined
      single cells were cut out after light microscopy. The HTLV-I DNA sequences were
      detected not only in ATL cells but also in normal-looking lymphocytes. This novel
      PCR method may provide a valuable tool for understanding the molecular events
      associated with HTLV-I infection at the single cell level.

PMID- 9766513
TI  - Apoptosis of leukemia cells induced by valine-deficient medium.

PMID- 9766514
TI  - Serum thrombopoietin levels in acute leukemia patients with chemotherapy-induced
      cytopenia--inverse correlation between serum levels and platelet counts.

PMID- 9766515
TI  - Multilineage dysplasia without increased blasts identifies a poor prognosis
      subset of myelodysplastic syndromes.

PMID- 9766516
TI  - Expression of two inward rectifier potassium channels is essential for
      differentiation of primitive human hematopoietic progenitor cells.
AB  - A potassium inward rectifier (K(ir)) current was previously shown by us to be
      induced in primitive hematopoietic progenitor cells, stimulated with the
      combination of interleukin-3 (IL-3) and stem cell factor (SCF). Biophysical
      features of whole cell currents implicated the involvement of more than one K(ir)
      channel type. Employing IL-3 + SCF stimulated human cord blood CD34+38- cells, we
      isolated and characterized different components of this current. Reverse
      transcription-polymerase chain reaction (RT-PCR) subcloning identified the
      expression of a strongly rectifying K(ir) channel (K(ir) 4.3) as well as a weakly
      rectifying K(ir) channel (K(ir) 1.1) in these cells. Inhibition of the expression
      of each of the channels suppressed progenitor cell generation by IL-3 and SCF
      stimulated CD34+38- cells in 7-day suspension cultures. The variable expression
      of two essential inward rectifying potassium channels early in the course of
      hematopoietic progenitor cell differentiation may play a potentially important
      role in potassium homeostasis in these cells.

PMID- 9766517
TI  - Cloning of murine CDK9/PITALRE and its tissue-specific expression in development.
AB  - The cdc2-family of serine/threonine kinases and their binding partners recently
      were implicated in developmental roles. We previously cloned a cdc2-related
      kinase, cdk9/PITALRE, that is able to phosphorylate the retinoblastoma protein in
      vitro. We describe here the cloning and the characterization of the mouse homolog
      of cdk9/PITALRE. The murine cDNA is 98% identical with humans and is expressed at
      high levels in brain and kidney tissues. The kinase activity and protein
      expression of cdk9/PITALRE were highest in terminally differentiated tissues such
      as the muscle and brain. In situ immunohistology and immunofluorescence detected
      cdk9/PITALRE protein not only within terminally differentiated cells such as
      muscle and neuronal cells, but also in proliferating cells. C2C12 and P19 cells
      induced to differentiate along muscle and neural lineages peaked in cdk9/PITALRE
      kinase activity at the end of differentiation. These results suggest that, among
      other roles, cdk9/PITALRE plays a role not unlike cdk5 in the differentiation of
      certain cell types.

PMID- 9766518
TI  - Transforming growth factor beta blocks cystogenesis by MDCK epithelium in vitro
      by enhancing the paracellular flux: implication of collagen V.
AB  - Transforming growth factor beta (TGFbeta) determines a nearly complete inhibition
      of cystogenesis by MDCK cells grown in collagen I-enriched matrices in vitro. In
      order to elucidate the mechanism implicated in this phenomenon, we performed a
      series of experiments aimed at discovering a relevant role of extracellular
      matrix. TGFbeta (2 ng/ml) played a marked stimulatory effect on the expression of
      extracellular matrix by MDCK with a selective effect on collagen V (three to
      fourfold increase of protein and mRNA) and in parallel inhibited cystogenesis by
      95%. Cotreatment with TGFbeta and anti-collagen V antibodies restored a normal
      cystogenesis. In analogy, when MDCK cells were grown in three-dimensional
      matrices containing collagen I and minor (10%) amounts of collagen V,
      cystogenesis was once again inhibited by 95%. To characterize the molecular
      mechanism activated by TGFbeta and collagen V, we looked at the
      electrophysiological characteristics of MDCK monolayers and found a drastic fall
      of transepithelial electrical resistance (TER) in both conditions. In parallel
      with the decrease in TER, TGFbeta and collagen V also induced the leakage of two
      high molecular weight tracers, i.e., [3H]-inulin and 150 kD FITC-Dextran,
      suggesting a perturbation of the paracellular permeability. Finally, TGFbeta at
      the relevant concentration did not stimulate apoptosis in our cellular model, as
      judged by propidium iodide staining and by in situ end labeling of DNA fragments.
      These observations suggest that TGFbeta inhibits cystogenesis by MDCK cells in
      vitro by altering the collagenic composition of the three-dimensional milieu
      where MDCK cells grow and form cysts. The molecular mechanism responsible for
      inhibition of cystogenesis is the increase of paracellular flux which overcomes
      the active transport of solutes and water inside cysts.

PMID- 9766519
TI  - Angiotensin II-stimulated collagen gel contraction by heart fibroblasts: role of
      the AT1 receptor and tyrosine kinase activity.
AB  - The accumulation and organization of extracellular matrix (ECM) components play
      critical roles in development, maintenance, and pathogenesis of most organ
      systems. These processes are regulated by the precisely orchestrated expression
      of ECM components, their receptors, and matrix proteases. The collagen gel
      culture system has been extensively used as a model to examine ECM remodeling
      similar to that which occurs during development and wound healing. Growth
      factors, including transforming growth factor-beta, platelet-derived growth
      factor, insulin-like growth factor, and angiotensin II, have been shown to
      stimulate collagen gel contraction. The present studies were undertaken to begin
      to examine the mechanisms through which angiotensin II stimulates collagen
      remodeling and gel contraction. These studies indicate that angiotensin II
      stimulates collagen gel contraction by isolated heart fibroblasts in a dose
      dependent manner and that this response is inhibited by the AT1 receptor
      antagonist Losartan. Furthermore, stimulation of collagen gel contraction by
      angiotensin II is also blocked by the src-related tyrosine kinase inhibitors
      genistein and herbimycin, indicating that activation of tyrosine kinases plays
      critical roles in this process. Stimulation of gel contraction by angiotensin II
      also involves the activation of JAK2, a member of the JAK/STAT pathways of
      transcriptional activation. Immunoprecipitation of surface-labeled fibroblasts
      indicate that cell surface levels of collagen-binding integrins also increase in
      response to angiotensin II treatment. Determining the underlying mechanisms
      regulating ECM remodeling is essential to understanding the role of ECM
      organization in development and disease.

PMID- 9766520
TI  - Differential kinetics for induction of interleukin-6 mRNA expression in murine
      peritoneal macrophages: evidence for calcium-dependent and independent-signalling
      pathways.
AB  - It is presently unclear what role elevations in intracellular calcium
      concentration ([Ca2+]i) play in the control of monokine secretion, or whether
      such alterations underlie the ability of physiologic stimuli to induce production
      of these important signalling molecules. To address these issues, we have
      performed experiments in murine peritoneal macrophages to determine whether
      lipopolysaccharide (LPS) or interferon gamma (IFN-gamma) initiate production of
      the proinflammatory monokine interleukin 6 (IL-6) concomitant with elevations in
      [Ca2+]i and with kinetics similar to that seen with known Ca2+ mobilizing agents.
      Alterations in [Ca2+]i after treatment with LPS, IFN-gamma, platelet activating
      factor (PAF), or thapsigargin were measured by fluorimetric methods. These
      effects were compared with the ability of each to induce IL-6 mRNA expression as
      measured by semiquantitative reverse-transcribed polymerase chain reactions. We
      report that neither LPS nor IFN-gamma elicited detectable elevations in [Ca2+]i
      but that both up-regulated expression of IL-6 mRNA expression within 60 min. In
      contrast, experiments using either thapsigargin or PAF showed rapid and dramatic
      elevations in [Ca2+]i with marked increases in IL-6 mRNA expression, as quickly
      as 15 min after initial exposure. Elevations in mRNA encoding IL-6 by
      thapsigargin and PAF were found to occur in a dose-dependent manner, mirroring
      their ability to elicit elevations in [Ca2+]i. These data demonstrate that LPS
      and IFN-gamma induce IL-6 message expression by means of Ca2+-independent
      signalling pathways. Furthermore, Ca2+-mobilizing agents that evoke monokine
      message expression do so far more rapidly than do LPS or IFN-gamma. Taken in
      concert, these data are consistent with the hypothesis that multiple signalling
      pathways exist by which production of proinflammatory monokines are initiated.

PMID- 9766521
TI  - Molecular cloning and tissue-specific expression of Mrad9, a murine orthologue of
      the Schizosaccharomyces pombe rad9+ checkpoint control gene.
AB  - We have isolated a murine cDNA, Mrad9, that is orthologous to the fission yeast
      rad9+ and human HRAD9 genes. Mrad9 encodes a 389 amino acid long, 42,032 Dalton
      protein that is 27% identical and 56% similar to Rad9p, and 82% identical and 88%
      similar to HRAD9, at the amino acid level. Expression of the Mrad9 cDNA in
      Schizosaccharomyces pombe rad9::ura4+ cells restores nearly wild-type levels of
      hydroxyurea resistance and early S phase checkpoint control to mutant fission
      yeast cell populations. However, UV resistance is only minimally restored, and
      mutant cells remain sensitive to gamma radiation. Mrad9 genomic DNA was isolated
      from a mouse 129/SvEv library. The Mrad9 gene was local ized to a 15-kbp genomic
      DNA fragment, and contains 10 exons separated by 9 introns. Northern blot
      analysis indicates that the gene is expressed in many different tissues of the
      adult mouse, but the mRNA is most abundant in the heart and present at very low
      levels in the liver. These studies demonstrate the existence of a murine
      orthologue of the fission yeast rad9+ gene and underscore at least the partial
      evolutionary conservation of rad9+-dependent checkpoint control mechanisms.

PMID- 9766522
TI  - Ammonia inhibits neural cell adhesion molecule polysialylation in Chinese hamster
      ovary and small cell lung cancer cells.
AB  - Ammonia is a major concern in biotechnology because it often limits recombinant
      protein production by animal cells. Conditions, such as ammonia accumulation, in
      large-scale production systems can parallel those that develop within fast
      growing solid tumors such as small cell lung cancer (SCLC). Ammonia's specific
      inhibition of the sialylation of secreted glycoproteins is well documented, but
      it is not known how ammonia affects membrane-bound proteins, nor what role it may
      have on important glycosylation determinants in cancer. We therefore examined the
      effects of NH4Cl on polysialic acid (PolySia) in the neural cell adhesion
      molecule (NCAM). By using flow cytometry combined with two NCAM antibodies, one
      specific for the peptide backbone and another that recognizes PolySia chains, we
      show that ammonia causes rapid, dose-dependent, and reversible inhibition of NCAM
      polysialylation in Chinese hamster ovary (CHO) and SCLC NCI-N417 cells. The
      decrease in PolySia was accompanied by a small increase in NCAM, suggesting that
      the changes were specific to the oligosaccharide. Inhibition by ammonia was
      greater for CHO cells, with PolySia cell surface content decreasing to 10% of
      control after a 4-day culture with 10 mM NH4Cl, while N417 cell PolySia was
      reduced by only 35%. Ammonia caused a 60% decrease in the CHO cell yield from
      glucose, while N417 cells were barely affected, suggesting that increased
      resistance to ammonia by N41 7 cells is a global rather than glycosylation
      specific phenomenon. The data presented show that the tumor microenvironment may
      be an important factor in the regulation of PolySia expression.

PMID- 9766523
TI  - Gamma-irradiation-induced cell cycle arrest and cell death in a human
      submandibular gland cell line: effect of E2F1 expression.
AB  - This study examined the effect of gamma-irradiation (5 and 10 Gy) on the human
      submandibular cell line (HSG). Radiation treatment (5 Gy and 10 Gy) induced a
      dose-dependent decrease in cell proliferation, with a G2/M arrest of the cell
      cycle, and an increase in cell death (cells with <2n DNA increased from 7% in
      control cells to 34% and 40% in 5 and 10 Gy irradiated cells, respectively).
      [Ca2+]i measurements demonstrated that the status of internal Ca2+ stores, and
      muscarinic receptor-mediated Ca2+ mobilization, in irradiated cells was
      comparable to that in non-irradiated cells. These data suggest that 1) irradiated
      HSG cells maintain normal physiology and 2) internal Ca2+ store depletion does
      not account for the decreased cell proliferation. To manipulate the radiation
      induced cell cycle arrest, we examined the effect of the transcription factor
      E2F1, which has been shown to induce cell cycle progression in HSG cells
      (Lillibridge and O'Connell, 1997, J. Cell. Physiol., 1 72:343-350). The ability
      of irradiated HSG cells to express and appropriately route proteins was
      demonstrated by using adenovirus-mediated expression of beta-galactosidase,
      alpha1-antitrypsin, and aquaporin-1. Infection of HSG cells with an adenoviral
      vector encoding E2F1, either 12 h before or immediately following irradiation,
      but not post-irradiation, induced maintenance of cells in the S phase of the cell
      cycle, reduced the number of cells arrested at G2/M, and decreased the rate of
      appearance of cells with <2n DNA. While the mechanism of irradiation-induced cell
      death has not yet been confirmed, these data suggest that expression of the E2F1
      gene product in HSG cells can be a useful strategy to manipulate cell cycle
      events and reduce the initial loss of cells due to radiation.

PMID- 9766524
TI  - Cellular characterization and successful transfection of serially subcultured
      normal human esophageal keratinocytes.
AB  - BACKGROUND: In vitro cell culture models can provide unique insights into
      squamous epithelial proliferation, differentiation, and neoplastic
      transformation. Cultures of human esophageal keratinocytes could be advantageous
      for the study of these processes. METHODS: Normal human esophageal keratinocytes
      were cultivated on 3T3 fibroblast feeder layers in vitro and expanded through
      four serial subcultivations. Confluent tertiary cultures were analyzed by
      morphological and immunohistochemical techniques to define their basic
      properties. The ability to transiently transfect cultured esophageal epithelium
      was tested using a Rous sarcoma virus-luciferase reporter gene by the calcium
      phosphate and lipofection methods. RESULTS: Postconfluent cultures displayed a
      predominantly basal cell phenotype with limited stratification, widespread
      expression of keratins 5 and 14, and production of attachment specialization
      proteins such as alpha6beta4 integrin and collagen VII. Terminal differentiation
      markers (involucrin and transglutaminase) were prematurely expressed. The cells
      expressed growth factors important in proliferation and differentiation, such as
      transforming growth factor-beta and interleukin-1beta. Tertiary cultures were
      successfully transiently transfected with a Rous sarcoma virus-luciferase
      reporter gene construct. CONCLUSION: Normal human esophageal cells can be
      serially passaged through extended numbers of cell generations and transfected by
      standard methods. This in vitro system may be useful in the study of fundamental
      cellular processes governing proliferation and differentiation in the esophageal
      epithelium.

PMID- 9766525
TI  - Down-regulation of epidermal growth factor receptor-signaling pathway by binding
      of GRP78/BiP to the receptor under glucose-starved stress conditions.
AB  - GRP78/BiP, a molecular chaperone in the endoplasmic reticulum, is induced under
      such adverse conditions for cell survival as glucose starvation. Induction of
      GRP78 has been shown to coincide with G1 cell cycle arrest, which is an important
      cellular defense system. In this study, we investigated involvement of GRP78 in
      the mechanism of growth arrest by using human epidermoid carcinoma A431 cells.
      Under a chemical stress condition with 2-deoxyglucose, GRP78 was induced 3-4
      fold. In the stressed cells, an underglycosylated form of epidermal growth factor
      receptor (EGFR) was produced and the mature form was decreased. We found that the
      molecular chaperone GRP78 in the endoplasmic reticulum formed a stable complex
      with the underglycosylated EGFR but did not with the mature form. This complex
      formation occurred specifically under the stress conditions, and the complex was
      dissociated upon removal of the stress. Treatment of the GRP78-underglycosylated
      EGFR complex with ATP resulted in a release of the underglycosylated EGFR from
      GRP78, indicating that the complex could be formed through the chaperone function
      of GRP78. In accordance with the complex formation with endoplasmic reticulum
      resident GRP78, the underglycosylated EGFR could not be translocated to the cell
      surface. As a result, EGF could not induce expression of cyclin D3, a G1 cyclin,
      in the stressed cells, whereas it did in non-stressed cells. These results
      indicated that, in the stressed cells, GRP78 participated in down-regulation of
      EGF-signaling pathway by forming a stable complex with EGFR and inhibiting EGFR
      translocation to the cell surface.

PMID- 9766526
TI  - Influence of calcium on proliferation and phenotype alteration of cardiomyocyte
      in vitro.
AB  - An accelerated weight gain is noted in the heart of Ca-deficient, hypertensive
      chick embryos maintained in a shell-less culture in vitro. We previously observed
      that the Ca handling property of cardiomyocytes isolated from the shell-less
      embryo is altered, i.e., faster Ca uptake, suggesting a requirement for adequate
      Ca supply and/or proper Ca handling in embryonic cardiac development. In this
      study, we have examined the function of Ca on cardiomyocytes by analyzing the
      effects of 1) various Ca concentration in the culture medium (NCa, 1.8 mmol/ L;
      HCa, 2.8 mmol/L; LCa, 0.9 mmol/L), and 2) various modulators of Ca handling on
      cell proliferation and phenotype regulation in chick embryonic cardiomyocytes.
      The analytical parameters included cell number, DNA content, expression of cell
      cycle-specific and cardiomyocyte-specific proteins, and creatine phosphokinase
      (CPK) and lactate dehydrogenase (LDH) enzyme activities. Cell number and total
      DNA were significantly larger (P < 0.01) in LCa cultures compared with those in
      NCa. The level of LDH was elevated (P < 0.01), but that of CPK was lowered in
      LCa. Expression of the G1-S-specific protein PCNA was raised, but that of the
      contractile proteins myosin and tropomyosin was substantially suppressed in LCa;
      in HCa, the cells did not proliferate as well, whereas the level of contractile
      proteins was higher. Thapsigargin, a sarcoplasmic reticulum (SR)-specific, Ca
      ATPase inhibitor, simulated the effects of LCa by enhancing cell proliferation
      and lowering the expression of tropomyosin. These results suggest that culturing
      in low Ca concentration and inhibition of SR Ca pumping enhance myocardial cell
      proliferation and suppress sarcomeric protein expression, perhaps by inducing
      cellular de-differentiation. The in vitro effects of medium Ca concentration and
      Ca handling modulators on cardiomyocytes also suggest that the in vivo
      cardiomegaly of the SL embryos is a direct result of Ca-deficiency, and that Ca
      is important in the phenotype regulation of cardiomyocytes.

PMID- 9766527
TI  - Expression of the NG2 proteoglycan enhances the growth and metastatic properties
      of melanoma cells.
AB  - The human homologue of NG2, the human melanoma proteoglycan (HMP), is expressed
      on most human melanomas. To investigate the role of this proteoglycan in melanoma
      progression, we have attempted to identify functionally important molecular
      ligands for NG2. Immunohistochemical analysis of cell lines that endogenously
      express NG2/HMP suggests that NG2/HMP associates with CD44 and alpha4beta1
      integrin, two molecules previously implicated in melanoma progression.
      Transfection of rat NG2 into the NG2-negative B16 mouse melanoma cell line also
      resulted in a highly colocalized pattern of expression between the transfected
      rat NG2 and the endogenously expressed mouse CD44 and alpha4beta1 integrin
      molecules. In functional assays, expression of NG2 decreased the adhesion of B16
      melanoma cells to CD44 monoclonal antibodies, hyaluronic acid, the C-terminal 40
      kDa fibronectin fragment, and the CS1 fibronectin peptide, suggesting that NG2
      may negatively modulate CD44- and alpha4beta1-mediated binding events. Expression
      of NG2 increased the proliferation of melanoma cells in culture and increased
      tumorigenicity in vivo. Moreover, NG2 expression led to increased lung metastasis
      of B16F1 and B16F10 melanoma cells in experimental metastasis studies. Together,
      these studies demonstrate that NG2 is capable of modulating the adhesion,
      proliferation, and metastatic potential of melanoma cells.

PMID- 9766528
TI  - Induction of interleukin-8 by ozone is mediated by tyrosine kinase and protein
      kinase A, but not by protein kinase C.
AB  - Ozone is one of the most common air pollutants humans routinely inhale. We have
      previously shown that in vitro ozone exposure induces the DNA-binding activities
      of NF-kappaB and NF-IL6 as well as the expression of interleukin 8 in respiratory
      epithelial cells. In this study, we investigated intracellular signaling steps
      mediating ozone-induced inflammatory mediator release. A549 cells, a type II like
      alveolar epithelial cell line, were exposed in vitro to air or 0.1 ppm of ozone
      in the presence of several kinase inhibitors. Exposure to ozone increased
      interleukin 8 expression and transcription factor activities in a protein
      tyrosine kinase (PTK)-dependent and protein kinase A (PKA)-dependent, yet protein
      kinase C (PKC)-independent, manner. Furthermore, ozone-induced PTK and PKA
      activities but failed to induce PKC activity. In addition, our results suggest
      that ozone-induced PTK and PKA activities were reactive oxygen intermediate
      dependent and occurred in parallel, because specific inhibitors for PTK and PKA
      failed to block the other kinase's activity. These results indicate that PTK and
      PKA activities are early events in the signal transduction cascade mediating the
      ozone-induced activation of NF-kappaB and NF-IL6 as well as the release of
      interleukin 8.

PMID- 9766529
TI  - Involvement of reactive oxygen species and caspase 3 activation in arsenite
      induced apoptosis.
AB  - Recent studies indicate that arsenic may generate reactive oxygen species to
      exert its toxicity. However, the mechanism is still unclear. In this study, we
      demonstrate that arsenite is able to induce apoptosis in a concentration- and
      time-dependent manner; however, arsenate is unable to do so. An increase of
      intracellular peroxide levels was accompanied with arsenite-induced apoptosis, as
      demonstrated by flow cytometry using DCFH-DA. N-Acetyl-L-cysteine (a thiol
      containing antioxidant), diphenylene iodonium (an inhibitor of NADPH oxidase),
      4,5-dihydro-1,3-benzene disulfonic acid (a selective scavenger of O2-), and
      catalase significantly inhibit arsenite-induced apoptosis and intracellular
      fluorescence intensity. In contrast, allopurinol (an inhibitor of xanthine
      oxidase), indomethacin (an inhibitor of cyclooxygenase), superoxide dismutase, or
      PDTC had no effect on arsenite-induced cell death. Activation of CPP32 activity,
      PARP (a DNA repair enzyme) degradation, and release of cytochrome c from
      mitochondria to the cytosol are involved in arsenite-induced apoptosis, and Bcl-2
      antagonize arsenite-induced apoptosis by a mechanism that interferes in the
      activity of CPP32. These results lead to a working hypothesis that arsenite
      induced apoptosis is triggered by the generation of hydrogen peroxide through
      activation of flavoprotein-dependent superoxide-producing enzymes (such as NADPH
      oxidase), and hydrogen peroxide might play a role as a mediator to induce
      apoptosis through release of cytochrome c to cytosol, activation of CPP32
      protease, and PARP degradation.

PMID- 9766530
TI  - Neurofibrosarcoma-derived Schwann cells overexpress platelet-derived growth
      factor (PDGF) receptors and are induced to proliferate by PDGF BB.
AB  - Neurofibromatosis type 1 (NF1) is characterized by the formation of
      neurofibromas, benign tumors of the peripheral nerve consisting essentially of
      Schwann cells, which can sometimes turn malignant to form neurofibrosarcomas. The
      mechanism of progression toward a malignant phenotype remains largely unknown. In
      this report, we show that platelet-derived growth factor (PDGF) BB, and to a
      lesser extent fibroblast growth factor 2, are mitogenic for two neurofibrosarcoma
      derived Schwann cell lines, but not for a Schwann cell line derived from a
      schwannoma (from a non-NF1 patient) or for transformed rat Schwann cells. Levels
      of expression of both PDGF receptor alpha and beta are significantly increased in
      the two neurofibrosarcoma-derived cell lines compared to the non-NF1 Schwann cell
      lines. The level of tyrosyl-phosphorylated PDGF receptor beta is strongly
      increased upon stimulation by PDGF BB. In comparison, only modest levels of
      tyrosyl-phosphorylated PDGF receptor alpha are observed, upon stimulation by PDGF
      AA or PDGF BB. Accordingly, PDGF AA is only a weak mitogen for the
      neurofibrosarcoma-derived cells by comparison to PDGF BB. These results indicate
      that the mitogenic effect of PDGF BB for the neurofibrosarcoma-derived Schwann
      cell lines is primarily transduced by PDGF receptor beta. Neu differentiation
      factor beta, a potent mitogen for normal Schwann cells, was unable to stimulate
      proliferation of the transformed Schwann cell lines, due to a dramatic down
      regulation of the erbB3 receptor. Therefore, aberrant expression of growth factor
      receptors by Schwann cells, such as the PDGF receptors, could represent an
      important step in the process leading to Schwann cell hyperplasia in NF1.

PMID- 9766531
TI  - Growth plate chondrocytes store latent transforming growth factor (TGF)-beta 1 in
      their matrix through latent TGF-beta 1 binding protein-1.
AB  - Osteoblasts produce a 100 kDa soluble form of latent transforming growth factor
      beta (TGF-beta) as well as a 290 kDa form containing latent TGF-beta binding
      protein-1 (LTBP1), which targets the latent complex to the matrix for storage.
      The nature of the soluble and stored forms of latent TGF-beta in chondrocytes,
      however, is not known. In the present study, resting zone and growth zone
      chondrocytes from rat costochondral cartilage were cultured to fourth passage and
      then examined for the presence of mRNA coding for LTBP1 protein. In addition, the
      matrix and media were examined for LTBP1 protein and latent TGF-beta. Northern
      blots, RT-PCR, and in situ hybridization showed that growth zone cells expressed
      higher levels of LTBP1 mRNA in vitro than resting zone cells. Immunohistochemical
      staining for LTBP1 revealed fine fibrillar structures around the cells and in the
      cell matrix. When the extracellular matrix of these cultures was digested with
      plasmin, LTBP1 was released, as determined by immunoprecipitation. Both active
      and latent TGF-beta1 were found in these digests by TGF-beta1 ELISA and Western
      blotting. Immunoprecipitation demonstrated that the cells also secrete LTBP1
      which is not associated with latent TGF-beta, in addition to LTBP1 that is
      associated with the 100 kDa latent TGF-beta complex. These studies show for the
      first time that latent TGF-beta is present in the matrix of costochondral
      chondrocytes and that LTBP1 is responsible for storage of this complex in the
      matrix. The data suggest that chondrocytes are able to regulate both the temporal
      and spatial activation of latent TGF-beta, even at sites distant from the cell,
      in a relatively avascular environment.

PMID- 9766533
TI  - Comparison of bax, waf1, and IMP dehydrogenase regulation in response to wild
      type p53 expression under normal growth conditions.
AB  - Recently, we demonstrated that downregulation of inosine-5'-monophosphate
      dehydrogenase (IMPD; IMP:NAD oxidoreductase, EC 1.2.1.14), the rate-limiting
      enzyme for guanine nucleotide biosynthesis, is required for p53-dependent growth
      suppression. These studies were performed with cell lines derived from immortal,
      nontumorigenic fibroblasts that express wild-type p53 conditionally by virtue of
      a metal-responsive promoter. Here, the p53-dependent properties of the original
      "p53-inducible" fibroblasts are presented in detail and compared to related
      properties of epithelial cells that also express wild-type p53 conditionally, but
      by virtue of a temperature-responsive promoter. Both types of p53-inducible cells
      were designed to approximate normal physiologic relationships between the host
      cell and the regulated p53 protein. Together, they were used to investigate
      expression relationships between IMPD and other p53-responsive genes proposed as
      mediators of p53-dependent growth suppression. In both types of cells, IMPD
      activity, protein, and mRNA were consistently coordinately reduced in response to
      p53 expression. In contrast, mRNAs for waf1, bax, and mdm2 showed disparate
      patterns of expression, being induced in one conditional cell type, but not the
      other. This distinction in regulation pattern suggests that under normal growth
      conditions, unlike IMPD downregulation, bax and waf1 induction is not a rate
      determining event for p53-dependent growth suppression.

PMID- 9766534
TI  - Are there risks in continuing education?

PMID- 9766532
TI  - Intracellular signaling of osteogenic protein-1 through Smad5 activation.
AB  - Smad proteins play pivotal roles in the intracellular signaling of the
      multifunctional transforming growth factor-beta (TGF-beta) family members
      downstream of serine/threonine kinase type I and type II receptors. Smad2 and
      Smad3 are specific mediators of TGF-beta and activin, while Smadl and Smad5 are
      involved in bone morphogenetic protein-2 (BMP-2) and BMP-4 signaling. Here we
      report that osteogenic protein-1 (OP-1), also termed BMP-7, binds predominantly
      to BMPR-IB in the rat osteoprogenitor-like cell line, ROB-C26. Smad1, Smad5, and
      Smad8, but not Smad2 and Smad3, were found to stably interact with the kinase
      deficient BMPR-IB after it was phosphorylated by the BMPR-II kinase. In ROB-C26
      cells, which express Smad2, Smad3, Smad4, and Smad5, OP-1 was found to stimulate
      the phosphorylation of Smad5. Whereas transfection of wild-type Smad5 enhanced
      the OP-1-induced response, transfection of wild-type Smad2 had no effect on OP-1
      signaling. A Smad5-2SA mutant, in which the two most carboxy-terminal serine
      residues were mutated to alanine residues, was found to act as a dominant
      negative inhibitor of OP-1-induced responses upon its transfection into various
      cell types, including ROB-C26 cells, in contrast to ectopic expression of a Smad2
      2SA mutant which was without effect. Smad5, therefore, is a key component in the
      intracellular signaling of OP-1.

PMID- 9766535
TI  - Comparison of propofol and methohexital continuous infusion techniques for
      conscious sedation.
AB  - PURPOSE: Methohexital and propofol have been shown to be effective agents for
      continuous intravenous infusion to produce conscious sedation during oral
      surgical procedures. The current study was conducted to compare these techniques
      for intraoperative cardiopulmonary stability, patient cooperation, amnesia,
      comfort, recovery time, and postoperative nausea and vomiting. METHODS: Seventy
      ASA Class I or Class II patients between the ages of 18 and 40 years, scheduled
      for surgical extraction of impacted third molars, were entered into the study.
      Thirty-five patients were assigned to group A (methohexital) and 35 were assigned
      to group B (propofol). Intravenous sedation was accomplished using premedication
      with 1.5 microg/kg of fentanyl and 0.05 mg/kg of midazolam followed by the
      continuous infusion of methohexital or propofol at a rate of 50 microg/kg/min.
      The infusion was then titrated to 100 microg/kg/min to accomplish a level of
      sedation in which the eyes were closed and the patients were responsive to verbal
      commands. Subjects were monitored for variability of heart rate, blood pressure,
      oxygen saturation, amnesia, comfort, cooperation, nausea and vomiting, and
      recovery time based on cognitive, perceptual, and psychomotor tests. RESULTS:
      There was no statistical difference between the two medication groups except for
      heart rate, which was found to increase by 11 beats/min for group A and only
      three beats/min in group B. CONCLUSION: A continuous infusion technique using
      either methohexital or propofol (50 to 100 microg/kg/min) was found to be safe
      and effective, with no clinically significant differences in cooperation,
      cardiopulmonary stability, recovery time, amnesia, comfort, and the incidence of
      nausea or vomiting. However, the cost-effectiveness of methohexital is superior
      to that of propofol.

PMID- 9766536
TI  - The use of ultrasonography as a diagnostic tool for superficial fascial space
      infections.
AB  - PURPOSE: This study examined the value of ultrasonography as a diagnostic tool in
      the treatment of superficial acute odontogenic fascial space infections. PATIENTS
      AND METHODS: The study group consisted of 50 patients in whom both radiographic
      and sonographic examinations, as well as a needle aspiration, were performed.
      RESULTS: Purulent fluid was aspirated in 22 of the 50 patients. Six patients
      diagnosed as suffering from cellulitis had a repeated ultrasonography scan. In
      four, abscess formation was diagnosed on the third day. CONCLUSIONS:
      Ultrasonography is an effective diagnostic tool to confirm abscess formation in
      the superficial fascial spaces and is highly predictable in detecting the stage
      of infection.

PMID- 9766537
TI  - Surgical management of temporomandibular joint ankylosis type III by retaining
      the displaced condyle and disc.
AB  - PURPOSE: This article proposes a hypothesis regarding the value of saving the
      fractured condyle and disc in their displaced position in ankylosis type III for
      optimal temporomandibular joint (TMJ) function and growth, and describes four
      cases treated in this manner. PATIENTS AND METHODS: Four patients (three females
      and one male, 9 to 48 years old) with TMJ ankylosis type III of 3 to 8 years'
      duration, a maximal mouth opening of 15 to 19 mm, and severely limited lateral
      and protrusive movements were treated. The ankylosed sites were resected, leaving
      the displaced condyle and disc in their medial position. RESULTS: Fifteen to 60
      months after surgery, the patients had a maximal mouth opening of 44 to 50 mm, as
      well as better contralateral and protrusive movements. In addition, two young
      patients (9 and 11 years old) showed an improved facial symmetry. CONCLUSIONS:
      Treatment of patients with type III TMJ ankylosis should involve retention rather
      than removal of the displaced condyle and disc. The condyle and disc are left
      untouched in their precarious medial position so as to provide normal function
      and growth.

PMID- 9766538
TI  - Contralateral coronoid process bone grafts for orbital floor reconstruction: an
      anatomic and clinical study.
AB  - PURPOSE: This study compares the contour of the coronoid process with the orbital
      floor using skulls and shows the use of this bone as a graft for orbital floor
      reconstruction. METHODS: Measurements and contour evaluations of the orbital
      floor and the contralateral mandibular coronoid process (12 right orbital floors
      with the lateral surface of the left coronoid process and 12 left orbital floors
      with the lateral surface of the right coronoid processes) were made in 24 dried
      adult human skulls (age, race, gender unknown) to assess the feasibility of using
      the mandibular coronoid process for orbital floor reconstruction. Applying the
      findings of this study, eight patients who had sustained either an isolated
      orbital floor blowout fracture (n = 2) or orbital floor compromise with an
      associated zygomatic bone fracture (n = 6) were treated by using their
      contralateral coronoid process for repair of the orbital floor. RESULTS: Anatomic
      Study: Measurements and contour comparisons of the right orbital floor with the
      left lateral cortex of the coronoid process in 12 skulls and the left orbital
      floor with the right lateral cortex of the coronoid process in the another 12
      skulls showed a close match in contour and demension. CLINICAL STUDY: Although
      minimal trimming of the peripheral bony margins and medial coronoid cortical
      plate was needed, none of the grafts required recontouring of their lateral
      cortical surface in the eight patients. Postoperative radiographic studies showed
      a correct anatomic contour of the orbital floor. A 1-year follow-up of each
      patient showed no occurrence of diplopia, enophthalmia, muscle entrapment, or
      infection. All eight patients had transient (1 to 2 weeks) trismus. CONCLUSION:
      Based on the anatomic studies and clinical results, the coronoid process makes an
      excellent donor graft site for reconstruction of orbital floor deformities.

PMID- 9766539
TI  - Blindness associated with midfacial fractures.
AB  - PURPOSE: This study assessed the frequency of blindness associated with midfacial
      fractures and correlated this with the fracture pattern. PATIENTS AND METHODS: A
      retrospective analysis of 49 patients admitted with midfacial fractures from
      January 1995 to March 1997 was performed to determine the presence of
      posttraumatic blindness. The medical and radiological records of the patients
      with blindness were reviewed for age and sex, cause of the injury, type of facial
      fracture, type of ocular trauma, and probable cause of the blindness. RESULTS:
      Ten of the 49 patients lost vision in one eye (20% of all midfacial fractures and
      22% of midface fractures involving the orbit). The possibility of blindness
      associated with facial fractures was directly related to the severity of injury.
      Road traffic accidents were the most common cause. Blindness was attributable to
      traumatic optic nerve injury in seven cases and a ruptured globe in three cases.
      CONCLUSIONS: The high frequency of blindness associated with midfacial fractures
      in this series was attributable to the predominance of road traffic accidents as
      the major cause and absence of an obligatory seat belt law. Early diagnosis of
      the exact nature of the ophthalmic injury and treatment are important, and
      involvement of the ophthalmologist is mandatory.

PMID- 9766540
TI  - Changing trends in the treatment of zygomaticomaxillary complex fractures: a 12
      year evaluation of methods used.
AB  - PURPOSE: The efficacy of the current methods for the treatment of fractures of
      the zygomaticomaxillary complex was evaluated. PATIENTS AND METHODS: One thousand
      two hundred seventy-seven patients with fracture of the zygomaticomaxillary
      complex and 196 patients with fractures of the zygomatic arch that were admitted
      between 1984 and 1995 were evaluated. One thousand one hundred fifty surgical
      procedures were performed, and in 401 cases, no operative treatment was
      considered necessary. The Gillie's approach was used in 514 cases, intraosseous
      wiring in 89 cases, bone plate osteosynthesis in 322 cases, Roger-Anderson pins
      in 180 cases, antral packing in 17 cases, and elevation with a hook in 28 cases.
      RESULTS: The best results were achieved with the use of semirigid fixation with
      miniplates applied at one or more sites of the fractured complex, occasionally
      used in combination with other methods such as Roger-Anderson pins. CONCLUSIONS:
      Semirigid fixation with miniplates offers the most reliable method available
      today for the treatment of zygomatico-orbital complex fractures and has
      practically replaced every other method in our institution. The increased cost
      and occasionally the necessity to remove the hardware are the main disadvantages
      of the method.

PMID- 9766541
TI  - A cadaveric study of maxillary sinus size as an aid in bone grafting of the
      maxillary sinus floor.
AB  - PURPOSE: This study measured maxillary sinus volume as an aid in determining
      graft bone volume before grafting of the maxillary sinus floor. MATERIALS AND
      METHODS: Maxillary sinus size was measured in 32 cadavers (59 sinuses) using
      casts of the maxillary sinus made using dental impression material. RESULTS:
      Anteroposterior length, height, width, and volume of the maxillary sinus (mean+/
      SD) were 30.1+/-5.65 mm, 34.6+/-7.71 mm, 25.4+/-5.71 mm, and 11.3+/-4.60 cm3,
      respectively. When the sinus-lift procedure was simulated, inferior sinus volumes
      (mean +/- SD) were 3.51+/-1.23 cm3 for a 15-mm lift and 5.66+/-1.71 cm3 for a 20
      mm lift. CONCLUSIONS: In bone grafting of the maxillary sinus floor, taking into
      consideration individual differences in maxillary sinus volume and resorption of
      the grafted bone, 4.74 cm3 or more of the graft is required for a 15-mm lift, and
      7.37 cm3 or more is required for a 20-mm lift.

PMID- 9766542
TI  - Anatomic and mechanical properties of the lateral disc attachment of the
      temporomandibular joint.
AB  - PURPOSE: This study measured the strength to failure of the human
      temporomandibular joint (TMJ) lateral disc attachment (LDA) using a tension
      compression machine. These data were correlated with the LDA location and its
      morphologic aspects, the age and sex of the subjects, and the amount of the
      lateral pterygoid muscle (LPM) inserted in the disc. METHODS: Forty-two TMJs
      without any obvious internal damage were carefully dissected to preserve the LDA.
      The width of insertion of the lateral pterygoid muscle fibers in the anterior
      band, as well as the width of the disc, were measured. The tension test was
      performed until the complete failure of the sample using a screw machine.
      RESULTS: Two types of LDA were recognized. In LDA 1, the anterior and posterior
      bands lateral disc junction were directly inserted on the lateral pole, whereas
      in LDA 2 this lateral junction was attached behind and below the pole through a
      sheet of fibrous tissue. The breaking points for LDA 1 (55.8 N) and LDA 2 (28.8
      N) were significantly different (P = .03). No correlation was found between the
      amount of LPM discal fibers insertion, sex, age, or the LDA breaking strength
      point. CONCLUSION: The LDA 2 insertion strongly suggests that the lateral joint
      ligament together with the capsule may act as a substitute for the original disc
      attachment to the lateral pole of the condyle.

PMID- 9766543
TI  - Histologic changes in the sinus membrane after maxillary sinus augmentation in
      goats.
AB  - PURPOSE: Previous studies have reported on the morphologic aspects of bone
      regeneration after maxillary sinus grafting. However, no previous studies have
      examinated the morphology of the maxillary sinus mucosa after grafting. The
      purpose of this study was to evaluate the histologic changes in the lining
      membrane after sinus augmentation. MATERIALS AND METHODS: A unilateral osteotomy
      of the lateral maxillary wall, medial displacement of the bony segments, and
      elevation of the sinus mucosa were performed in 12 goats. An autogenous bone
      graft combined with coralline particles was placed on the floor of the sinus in
      three animals, and coralline particles alone were placed in three other goats.
      Six goats were not grafted and were used as controls. Samples were harvested at
      2.5, 4.5, and 6.5 months. The maxillary sinus mucosa was examined using light
      microscopy and scanning and transmission electronic microscopy. RESULTS: The
      coralline particles were surrounded by fibrous connective tissue when used alone.
      The addition of iliac crest bone to the coralline particles stimulated bone
      formation. After the sinus augmentation, the mucosal lining showed a lack of
      glands in the lamina propria, and the epithelium showed an increase in goblet
      cells. CONCLUSION: It was concluded that the sinus mucosa undergoes physiologic
      adaptations and remains healthy and free of chronic sinusitis after maxillary
      sinus grafting.

PMID- 9766544
TI  - Chronic, progressive limitation of mouth opening.

PMID- 9766545
TI  - Ameloblastoma of the mandible involving an autogenous bone graft.

PMID- 9766546
TI  - Mandibular malignant schwannoma with multiple spinal metastases: a case report
      and a review of the literature.

PMID- 9766547
TI  - An unusual tumor of the mandible with features of unicystic ameloblastoma and
      ameloblastic fibroma.

PMID- 9766548
TI  - Bilateral oral commissurotomy using buccal mucosa flaps for management of
      microstomia: report of a case.

PMID- 9766549
TI  - Tongue necrosis in a patient with temporal arteritis.

PMID- 9766550
TI  - Intramuscular myxoma of the temporalis muscle.

PMID- 9766551
TI  - Osteopetrosis: a review of the literature and report of a case complicated by
      osteomyelitis of the mandible.

PMID- 9766552
TI  - Preservation of the inferior alveolar nerve in the surgical approach to cancer of
      the posterior oral cavity.

PMID- 9766553
TI  - A technique for improving the handling of particulate cancellous bone and marrow
      grafts using platelet gel.

PMID- 9766554
TI  - The use of dogs for experimentation.

PMID- 9766555
TI  - The use of dogs for experimentation.

PMID- 9766556
TI  - Risks of brain tumour following treatment for cancer in childhood: modification
      by genetic factors, radiotherapy and chemotherapy.
AB  - A cohort of 4,400 persons treated for various cancers of childhood in France and
      the UK was followed up over an extended period to assess risks of subsequent
      brain tumour in relation to the radiotherapy and chemotherapy that the children
      received for their first cancer. Elevated risks of subsequent brain tumours were
      associated with first central nervous system (CNS) tumour (two-sided p = 0.0002)
      and neurofibromatosis (two-sided p = 0.001). There was also elevated brain tumour
      risk (two-sided p = 0.003) associated with ionising radiation exposure, the risk
      being concentrated among benign and unspecified brain tumours. The radiation
      related risk of benign and unspecified brain tumours was significantly higher
      than that of malignant brain tumours (two-sided p< or =0.05); there was no
      significant change of malignant brain tumour risk with ionising radiation dose
      (two-sided p > 0.2). In general, there were no strong associations between
      alkylating agent dose and brain tumour risk. The only significant association
      between brain tumour risk and alkylating agent dose was in relation to compounds
      used (bleomycin, chloraminophen) that are thought not to deliver substantial
      doses to the brain; the statistical significance of the trend with dose depended
      on a single case, and thus must be considered a weak result.

PMID- 9766557
TI  - Body site distribution of cutaneous malignant melanoma in relationship to
      patterns of sun exposure.
AB  - A study of all newly incident melanoma patients in British Columbia in 1991-1992
      was undertaken to test the hypothesis raised by an earlier study, which showed
      that in younger patients the incidence rate of melanoma per unit area of skin was
      higher on intermittently exposed skin areas than on continuously exposed areas.
      Using 1,033 patients and a more detailed body site categorisation than was
      previously possible, our results confirmed that in both men and women under age
      50 the highest melanoma density was on the back. At ages over 50, the greatest
      density occurred on fully exposed sites, such as the face, though the dorsum of
      the hand and forearm, likely also to have high exposure, show very low melanoma
      densities. Differences between males and females correlate well with differences
      in likely exposure patterns. These results were seen for all invasive cutaneous
      melanomas combined; the patterns were similar for subtypes and for both invasive
      and in situ melanoma, with the exception of lentigo maligna melanoma (LMM), which
      occurs almost exclusively on the face, even at younger ages. Comparison with the
      earlier study (1976-1979) shows that the age-standardised rates for melanoma
      excluding LMM have increased by 60%, with the greatest proportional increase
      being at younger ages; in the recent data, the age-standardised rate for
      intermittently exposed sites exceeds that for usually exposed sites. Our results
      confirm that intermittent sun exposure has a greater potential for producing
      melanoma than continuous exposure at ages below about 50, though at older ages
      melanoma is more common on body sites with continuous sun exposure.

PMID- 9766558
TI  - HPV 16 and cigarette smoking as risk factors for high-grade cervical intra
      epithelial neoplasia.
AB  - Although genital human papillomavirus (HPV) infection is well established as the
      etiologic agent for cervical intraepithelial neoplasia (CIN), little is known
      about the cofactors involved in the development of high-grade lesions or the
      progression of low-grade to high-grade lesions. In our study of HPV-infected
      women with CIN (163 CIN I, 51 CIN II and 44 CIN III), women with CIN II or III
      were compared with those with CIN I for risk factors associated with high-grade
      lesions. After controlling for age, education, ethnicity and frequency of Pap
      smear screening, infection with HPV 16, but not high viral load or infection with
      multiple types, was associated with high-grade lesions (OR for CIN II = 11.96, OR
      for CIN III = 23.74). Risk of CIN III, but not CIN II, increased with number of
      cigarettes smoked per day (ORs = 1.49 and 3.35 for < or = 10 and > 10 cigarettes
      per day, respectively) and decreased with frequency of condom use during sex (ORs
      = 0.60 and 0.32 for women who used condoms occasionally/sometimes and most/all of
      the time, respectively). There were no associations between high-grade lesions
      and plasma levels of micronutrients (retinol, beta-carotene, alpha-tocopherol and
      reduced ascorbic acid). Our results indicate that infection with HPV 16 is
      associated with high-grade lesions. Additional cofactors, such as cigarette
      smoking, may be required as a carcinogen to advance HPV-infected cells toward
      neoplastic progression.

PMID- 9766559
TI  - Cancer cells overexpress mRNA of urokinase-type plasminogen activator, its
      receptor and inhibitors in human non-small-cell lung cancer tissue: analysis by
      Northern blotting and in situ hybridization.
AB  - The transcriptional localizations of urokinase-type plasminogen activator (uPA),
      its receptor (uPAR) and its inhibitors (PAI-1 and PAI-2), which are possibly
      involved in cancer metastasis, have not been determined in human lung cancer. To
      identify their regulation in primary non-small-cell lung cancer, we assayed mRNA
      levels by Northern blot analysis in 25 cases and determined the localizations of
      mRNA by in situ hybridization in 10 cases. The amounts of uPA and PAI-2 mRNA were
      significantly higher in cancerous relative to normal lung tissues. However, no
      significant difference was observed in uPAR and PAI-1 mRNA levels. All
      transcripts were present in cancer cells and were predominantly located in tumor
      edges in several cases. In addition, PAI-1 transcripts were more abundant in
      poorly and moderately differentiated carcinomas relative to well-differentiated
      carcinomas and PAI-2 transcripts were more abundant in squamous cell carcinomas
      than in adenocarcinomas. Thus, PAIs may be involved in modulation of malignant
      potency. Our results indicate that human non-small-cell lung cancer cells can
      autonomously express the mRNAs of uPA, uPAR and PAIs, which are possibly involved
      in metastasis.

PMID- 9766561
TI  - Infection with CagA+ Helicobacter pylori strains as a possible predictor of risk
      in the development of gastric adenocarcinoma in Mexico.
AB  - Helicobacter pylori strains possessing the Cag pathogenicity island have been
      associated with increased gastric inflammation and with duodenal ulcer. In
      contrast, studies on the association of cagA+ H. pylori infections and gastric
      cancer have shown conflicting results. The aim of our study was to determine
      whether H. pylori and CagA status are associated with gastric cancer in Mexico.
      We selected serum samples from 3 geographic areas with gastric cancer mortality
      rates per 100,000 inhabitants of 2.5 (low risk), 4.5 (medium risk) and 6.4 (high
      risk). H. pylori infection was determined by the detection of antibodies to H.
      pylori whole cell antigen by an enzyme-linked immunosorbent assay (ELISA). To
      study the prevalence of infection with cagA+ strains, serum IgG antibodies to
      CagA were determined by ELISA using a recombinant CagA antigen. Of the 2,775
      individuals studied, 1,931 were H. pylori seropositive and 1,710 had antibodies
      against CagA. The risk for gastric cancer in the 3 populations studied increased
      proportionally as infection with cagA+ strains increased (p < 0.001 for trend).
      H. pylori infection also showed association with gastric cancer (p < 0.05).
      Individuals seropositive for CagA, but seronegative for H. pylori whole cell
      antigen, were more frequent in areas with higher gastric cancer rates (p < 0.01).
      These results support the possible role of CagA(+) status as predictor of risk
      for gastric adenocarcinoma in Mexico; this is in agreement with results in
      European and American populations, but contrary to studies in some Asian
      countries.

PMID- 9766560
TI  - Familial prostate cancer and possible associated malignancies: nation-wide
      register cohort study in Sweden.
AB  - There is a familial aggregation of prostate cancer, and 5 to 10% of all prostate
      cancers are estimated to be inherited in an autosomal-dominant mode. A population
      based cohort study was performed in order to study familial prostate cancer and
      associated malignancies. A nation-wide register cohort study was conducted using
      an unselected study population. The cohort of 5,595 sons and 5,089 daughters of
      Swedish men found to have prostate cancer between 1959 and 1963 was identified.
      All types of cancer reported between 1958 and 1992 in this cohort were identified
      through linkage to the Swedish Cancer Registry. The expected number of different
      cancers was calculated using incidence rates obtained from the Registry. A highly
      significant increased overall standardized incidence ratio (SIR) of 1.65 (95% CI,
      1.49-1.83) was obtained for prostate cancer, with 370 observed cases compared
      with 224 expected prostate cancers. The SIR was 3.18 among cases 45 to 49 years
      old at diagnosis, with the risk gradually decreasing to a SIR of 1.45 among cases
      over 80 years of age. Among sons and daughters with a father whose prostate
      cancer was diagnosed at an early age (<70 years), an increased risk for
      colorectal cancer SIR 1.48 (1.10-1.95) was observed. No significant difference in
      cancer risk for other sites was observed among the daughters and sons of men with
      prostate cancer. This cohort study confirms earlier studies that a positive
      family history of prostate cancer is an important risk factor for developing this
      disease. Though increased risk was found for all ages, it was more pronounced in
      younger men. Since no other malignancy was significantly associated with prostate
      cancer, it is most likely that familial prostate cancer is "site-specific".

PMID- 9766562
TI  - Expression of signal transducing T-cell receptor zeta molecules after adoptive
      immunotherapy in patients with gastric and colon cancer.
AB  - We and others have shown decreased expression of T-cell receptor-CD3-associated
      signal transducing zeta molecules (TCRzeta) in tumor infiltrating and peripheral
      T cells of patients with advanced cancer. In the present study, we performed
      adoptive immunotherapy (AIT) with tumor-associated lymphocytes (TAL) in patients
      with gastric (n = 11) and colon (n = 3) cancer with stage IV and investigated
      whether the alteration of signal transducing molecules was observed with AIT,
      compared to an untreated control group (n = 13). Autologous TALs isolated from
      malignant ascites or pleural effusion were cultured with stimulation of
      autologous tumor in the presence of interleukin-2 (IL-2) and were transferred to
      the patients. TCR zeta expression in peripheral T cells was measured by flow
      cytometric analysis of permeabilized cells with anti-zeta monoclonal antibody
      (MAb) (TIA-2) before and after AIT. We confirmed the down-regulation of TCR zeta
      expression in peripheral blood lymphocytes (PBL) of patients with gastric and
      colon cancer with stage IV compared to healthy donors (n = 15). AIT induced up
      regulation of TCR zeta expression in 2 of 14 treated patients, caused no
      significant change of TCR zeta expression in 7 patients and induced further down
      regulation in 5 patients. The patients who achieved clinical responses (n = 3)
      with AIT showed no significant change of TCR zeta expression. On the other hand,
      in the control group without adoptive transfer, further down-regulation of TCR
      zeta expression was observed during the corresponding periods, paralleling
      disease progression. Taken together, TCR zeta expression in the patients was
      further down-regulated, corresponding to disease progression in individual cancer
      patients. In some patients, AIT could induce increased or stable TCR zeta
      expression. The quantitative analysis of TCR zeta expression might provide vital
      information that can be used to optimize therapy by preserving immune functions
      within cancer patients.

PMID- 9766563
TI  - Expression of the ATM gene is significantly reduced in sporadic breast
      carcinomas.
AB  - The gene mutated in ataxia telangiectasia (A-T) patients (ATM) is located on
      chromosome 11q22-23, a region frequently altered in mammary tumors. Patients
      homozygous for ATM mutations are prone to develop a variety of different
      neoplasms. Female heterozygotes have been reported to carry a 5- to 8-fold
      increased risk of breast cancer. However, germline mutations in the ATM gene are
      rare in women with sporadic breast carcinomas. Most of the alterations described
      in A-T patients result in a functionally inactive ATM protein. Moreover, it has
      been suggested that mutations of the ATM gene in A-T patients influence the
      amount of ATM mRNA and that this may affect the severity of the disease. In the
      present study, we have analyzed ATM transcripts in a series of 39 breast
      carcinomas, 14 benign breast lesions and 12 normal breast tissue samples. ATM
      mRNA levels were determined by semiquantitative competitive RT-PCR. Competitor
      RNA molecules for the ATM gene and the housekeeping gene beta-2-microglobulin
      (B2M) were generated by PCR mutagenesis. Low concentrations of ATM transcripts
      were detected in breast carcinomas, intermediate levels in benign lesions and
      highest levels in normal breast tissue specimens (F-test, p = 0.0013). Our
      results indicate that reduced expression of the ATM gene may contribute to the
      development and/or malignant progression of breast carcinomas.

PMID- 9766565
TI  - Prognostic factors for cutaneous malignant melanoma in Vaud, Switzerland.
AB  - We considered, by means of a multivariate approach, trends in survival from
      cutaneous malignant melanoma in relation to patient and tumor characteristics,
      using data from the Cancer Registry of the Swiss Canton of Vaud. Between 1980 and
      1994, 1,229 cases of incident cutaneous malignant melanoma were registered. There
      was a decline in the proportion of neoplasms in the head and neck and lower
      limbs, and a rise in those of the trunk and upper limbs, an increase in
      superficial spreading melanoma and in tumors of limited thickness, mostly in
      females. Five-year crude survival was 0.68 for males and 0.82 for females, and
      relative survival of 0.79 for males and 0.89 for females, corresponding to a
      multivariate hazard ratio (HR) of 0.63 for females vs. males. Survival was
      inversely related to age, with 5-year relative survival of 0.92 at age 15-44
      years, 0.85 at age 45-64 years, and 0.79 at age > or = 65 years. With reference
      to histological type, no significant difference was observed in males, but in
      females nodular melanoma showed reduced survival. Compared with melanoma of the
      limbs, the HR was 1.46 for melanoma of the trunk, and 1.23 for those in the head
      and neck, and the difference was greater in females. A strong relation, in both
      sexes, was observed between survival and tumor thickness, with an HR of 3.96 for
      tumors > or = 4 mm vs. those < 1.50 mm. After allowance for all other factors
      considered, most recent calendar period of diagnosis was associated with improved
      survival in both sexes (HR = 0.72), but mostly in females. Although differences
      in survival tended to be larger during the first 2 years after diagnosis, the
      pattern was similar for most prognostic factors considered up to 10 years after
      diagnosis.

PMID- 9766564
TI  - Pharmacokinetics and selectivity of aminolevulinic acid-induced porphyrin
      synthesis in patients with cervical intra-epithelial neoplasia.
AB  - Photodynamic therapy (PDT), due to its tumor selectivity, represents an
      alternative approach to diagnose and treat cervical intra-epithelial neoplasia
      (CIN) without altering normal surrounding tissue. Our aim was to investigate the
      pharmacokinetics and the selectivity of 5-aminolevulinic acid (5-ALA)-induced
      porphyrin fluorescence after topical administration, to obtain basic clinical
      data for future diagnostic fluorescence imaging and PDT protocols for CIN. Twenty
      eight non-pregnant women with a cytological diagnosis of low-grade or high-grade
      squamous intra-epithelial lesions were included. An aqueous solution containing
      3% 5-ALA was topically applied 1 to 6 hrs prior to conization using a cervical
      cap. After excision, porphyrin-induced fluorescence was quantified in dysplastic
      (n = 14) and normal epithelium (n = 28) by means of quantitative fluorescence
      microscopy. High values of porphyrin fluorescence were found in squamous
      epithelium between 150 and 450 min, with a maximum at 300 min following
      administration of 5-ALA. Ratios of porphyrin fluorescence of dysplastic vs.
      surrounding normal epithelium were 1.3 and 1.21 for CIN 1 (n = 3) and CIN 2 (n =
      3), respectively. In CIN 3 patients (n = 8), this ratio was 2.35; the best
      selectivity of 5-ALA-induced porphyrin fluorescence in CIN 3 lesions (ratio 3)
      was observed with a topical administration time of between 150 and 250 min. Our
      results demonstrate that patients with CIN 3 show higher 5-ALA-induced
      fluorescence compared with normal epithelium. The optimal administration time of
      topically applied 5-ALA was between 3 and 4 hr. Our data suggest that topical ALA
      PDT and photodynamic diagnosis might be suitable for detecting CIN.

PMID- 9766566
TI  - Analysis of fibrinolytic proteins in relation to DNA ploidy in prostate cancer.
AB  - The tissue concentrations of urokinase-type plasminogen activator (u-PA),
      urokinase-type plasminogen activator receptor (u-PAR), plasminogen activator
      inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were
      investigated by an ELISA technique in normal and malignant samples of the
      prostate from 24 patients undergoing radical prostatectomy for organ-confined
      prostate cancer. The median concentration of u-PA was significantly higher in
      cancerous than in normal prostate tissue (p = 0.006). No significant increase of
      u-PAR, PAI-1 and t-PA was found in cancer tissue in comparison with the benign
      samples (p > 0.05). Assessment of the relationship between fibrinolytic proteins
      and DNA ploidy revealed an increased u-PA, u-PAR and PAI-1 in diploid prostate
      cancer as compared with the normal controls. However, in aneuploid cancer u-PA
      remained high but u-PAR and PAI-1 were decreased. This led to a higher local
      concentration of u-PA in aneuploid samples than in normal prostate and in diploid
      prostate cancer. No alteration of median t-PA was found in benign prostate or in
      diploid or aneuploid prostate cancer. The altered expression of u-PA, u-PAR and
      PAI-1 in diploid and aneuploid prostate cancer suggests a possible role of
      fibrinolytic proteins in the different biologic behavior of tumors, and may be
      one explanation for the higher metastatic potential of aneuploid tumors.

PMID- 9766567
TI  - STAT3 mediates the survival signal in oncogenic ras-transfected intestinal
      epithelial cells.
AB  - The oncogenic ras mutation is a common and critical step in gastrointestinal
      carcinogenesis. In a previous study, we demonstrated that oncogenic ras activated
      the EGF-related peptide autocrine loop and that the apoptosis resistance observed
      in the oncogenic ras-stimulated cell (IEC-ras cell) was dependent on this
      activated EGF-related peptide autocrine loop. STATs (signal transducers and
      activators of transcription), first identified as intracellular signal
      transducers stimulated by cytokines, are known to also be activated by EGF.
      However, the role of STATs in the survival signal of IEC-ras cells is not clear.
      In the present study, we demonstrate that STAT3 is constitutively activated in
      ras-stimulated cells and that STAT3 activation is considerably suppressed by the
      EGF-specific receptor kinase inhibitor AG 1478. We also show that disruption of
      the STAT3 pathway by introduction of a dominant-negative STAT3 mutant abolishes
      the apoptosis resistance against UVC and MMC treatment observed in IEC-ras cells
      without affecting proliferation. Moreover, the expression of Bcl-2 and Bcl-xL,
      apoptosis-suppressive proteins, is reduced in dominant-negative STAT3-transfected
      cells. Thus, STAT3 appears to be an important mediator of the antiapoptotic
      signal in IEC-ras cells.

PMID- 9766568
TI  - Proteinase requirements of epidermal growth factor-induced ovarian cancer cell
      invasion.
AB  - Aberrant expression or activity of the epidermal growth factor (EGF) receptor
      family of tyrosine kinases has been associated with tumor progression and an
      invasive phenotype. In this study, we utilized 4 ovarian cancer cell lines, OVCA
      432, DOV 13, OVEA6 and OVCA 429, to determine the effects of EGF on the
      regulation of proteolytic enzymes and their inhibitors, cellular migration and in
      vitro invasion. Induction of urinary-type plasminogen activator (u-PA) activity
      and tissue inhibitor of matrix metalloproteinase (TIMP)-1 was observed in all 4
      cell lines. OVCA 432 cells showed strong PAI-1 induction; however, the other 3
      lines displayed substantial baseline PAI-1 expression that was not induced by
      EGF. EGF-dependent stimulation of migration and induction of matrix
      metalloproteinase (MMP)-9 (gelatinase B) was observed in OVEA6 and OVCA 429 cells
      only. Upon EGF receptor activation, DOV 13, OVEA6 and OVCA 429 cells were induced
      to invade through an artificial basement membrane (Matrigel); however, no
      invasion was detected in OVCA 432 cells. Cell lines displaying induction of
      migration and MMP-9 (OVEA6 and OVCA 429) demonstrated robust EGF-induced invasion
      (5- to 20-fold), and cell invasion was substantially reduced in the presence of
      anti-catalytic MMP-9 antibody. Addition of anti-catalytic u-PA antibody inhibited
      the modest (<2-fold) EGF-induced invasion in a cell line that did not express MMP
      9 (DOV 13) and in OVEA6 cells that displayed the highest baseline u-PA activity.
      Together, our findings indicate that multiple proteinases are important in
      ovarian cell invasion and implicate EGF induction of MMP-9 and migration as key
      components of more aggressive ligand-induced invasion.

PMID- 9766569
TI  - Anti-proliferative effect of retinoids and interferon-alpha-2a on vaginal cell
      lines derived from squamous intra-epithelial lesions.
AB  - A panel of retinoids (all-trans-, 13-cis-, 19-cis retinoic acid and acitretin),
      and interferon-alpha-2a was tested for the capacity to modulate the proliferation
      of UT-DEC-1 (HPV-33-positive) and UT-DEC-2 (HPV-16-positive) cell lines derived
      from vaginal intra-epithelial neoplasias (VAIN). At concentrations 10(-6) to 10(
      8) M, all retinoids inhibited the growth of early-passage UT-DEC cell lines, but
      also of normal vaginal keratinocytes and fibroblasts. The inhibition was
      significantly reduced in late-passage UT-DEC cells. The effect on proliferation
      was essentially equal for all retinoids in high (1.8 mM)-Ca2+ medium, but
      decreased markedly in low (0.09 mM)-Ca2+ medium. Interferon-alpha-2a at 1000
      IU/ml had an additive growth-inhibitory effect in the low- and in the high-Ca2+
      medium. No consistent decrease in HPV E6-E7 mRNA levels could be associated
      either with retinoid or with interferon effect in either cell line. The
      expression of TGFbeta1 and TGFbeta2 mRNA increased 2- to 3-fold by 10(-6) M 13
      cis-RA treatment in early- and in late-passage cells of both cell lines. TGFbeta1
      at 0.1 to 1.0 ng/ml also inhibited the proliferation of both cell lines, and was
      more effective at early passage, but the inhibition was not dependent on calcium
      concentration. Neutralizing anti-TGFbeta antibodies partially relieved the
      proliferation inhibition by 13-cis-RA. The results show that the calcium
      associated regulation of growth by the tested retinoids was seen in normal
      vaginal cells and in early pre-neoplastic cells, but was significantly reduced in
      cells with higher-grade phenotype, while also suggesting that the loss of
      responsiveness to retinoids and TGFbeta may play a role in the progression of
      squamous intra-epithelial neoplasia.

PMID- 9766570
TI  - DNA interaction and cytostatic activity of the new liver organotropic complex of
      cisplatin with glycocholic acid: Bamet-R2.
AB  - The aim of this study was to investigate the ability of the new liver
      organotropic complex of cisplatin with glycocholate (GC), Bamet-R2, to interact
      with DNA, inhibit its replication and hence reduce tumor-cell proliferation.
      Changes in the electrophoretic mobility of the open and covalently closed
      circular forms of the pUC18 plasmid DNA from Escherichia coli, a shift in the
      denaturation temperature of double-stranded DNA, and ethidium-bromide
      displacement from DNA binding, were induced by Bamet-R2 and cisplatin, but not by
      GC. Neutral-red retention was used to measure the number of living cells in
      culture after long-term (72-hr) exposure to these compounds and to evaluate the
      effect on cell viability after short-term (6-hr) exposure. Bamet-R2 and
      cisplatin, but not GC, induced significant inhibition of cell growth. This effect
      ranged from mild to strong, depending upon the sensitivity of the different cell
      types as follows: cisplatin, rat hepatocytes in primary culture < rat hepatoma
      McA-RH7777 cells (rH) < human colon carcinoma LS 174T cells (hCC) < mouse
      hepatoma Hepa 1-6 cells (mH); Bamet-R2, rat hepatocytes < mH approximately equal
      to hCC < rH. DNA synthesis was measured by radiolabeled-thymidine incorporation
      into DNA. Bamet-R2 and cisplatin, but not GC, significantly inhibited the rate of
      DNA synthesis by these cells. After short-term exposure to Bamet-R2 or GC, no
      acute cell toxicity was observed, except on hCC cells. By contrast, acute
      toxicity was induced by cisplatin for all cell types studied. The in vivo anti
      tumoral effect was investigated in 3 different strains of mice following s.c.
      implantation of tumor cells (mouse sarcoma S-18011 cells in Swiss and B6 mice and
      hCC cells in nude mice). In all 3 models, tumor growth was inhibited by Bamet-R2
      and cisplatin to a similar degree. However, signs of toxicity (increases in blood
      urea concentrations and decreases in packed blood cell volume and in liver,
      kidney and body weight) and a reduction in survival rate were observed only
      during cisplatin administration. In sum, these results indicate that this bile
      acid derivative can be considered as a cytostatic drug whose potential usefulness
      deserves further investigation.

PMID- 9766571
TI  - Hyperglycemia regulates the glucose-transport system of clonal choriocarcinoma
      cells in vitro. A potential molecular mechanism contributing to the adjunct
      effect of glucose in tumor therapy.
AB  - Glucose is taken up by tumor cells via sodium-independent facilitated diffusion
      along a concentration gradient. To examine the regulation of this process by
      substrate concentration, we investigated the effect of hyperglycemia on the
      glucose-transport system of choriocarcinoma-derived JAR and JEG-3 cells by
      culturing them for 24, 48 and 96 hr in medium containing either 5.5
      (normoglycemia) or 25 (hyperglycemia) mM D-glucose, respectively.
      Immunocytochemically, choriocarcinoma cells expressed the high-affinity glucose
      transporter isoforms GLUT1 and GLUT3. Based on initial uptake measurements using
      3-O-[14C]methyl-D-glucose, kinetic parameters were calculated as Km = 15 mM and
      Vmax = 95 fmol/sec per cell for JAR and Km = 9 mM and Vmax = 64 fmol/sec per cell
      for JEG-3 cells. In JAR cells cultured under hyperglycemic conditions, uptake
      rates were significantly increased at 15, 20 and 25 mM exogenous D-glucose
      concentrations as compared with normoglycemic conditions. This effect was due to
      an increase in Vmax, whereas Km remained unchanged. Using Northern blotting,
      GLUT1 mRNA levels were higher but GLUT3 transcripts were reduced upon
      hyperglycemia. Western blotting revealed elevated GLUT1 and GLUT3 expression
      under hyperglycemic conditions. Hyperglycemia did not significantly influence the
      glucose-transport system of JEG-3 cells. We conclude that sustained hyperglycemia
      stimulates the glucose-transport system of JAR, but not of JEG-3, choriocarcinoma
      cells in vitro due to changes in GLUT1 and GLUT3 expression levels. We speculate
      that this mechanism may contribute to the beneficial effects of induced
      hyperglycemia as an adjuvant in tumor therapy.

PMID- 9766572
TI  - IL-12 regulates VEGF and MMPs in a murine breast cancer model.
AB  - In a murine model of breast cancer, IL-12 therapy exerts potent anti-angiogenic
      effects which contribute to tumor regression. After 7 days of treatment, levels
      of tumor VEGF protein decline markedly and are undetectable at 14 days. This
      decline is accompanied by a fall in MMP-9 and, as the tumors regress, an increase
      in its natural inhibitor, TIMP-1. A cell line established from the primary tumor
      produced VEGF in vitro. IFN-gamma reduced tumor cell production of VEGF over a 24
      hr period in vitro, suggesting that IL-12-induced IFN-gamma may be responsible
      for the decline in VEGF levels in vivo. There is also in vitro evidence that IL
      12 regulates stromal cell interactions, leading to decreased MMP-9 and increased
      TIMP-1 production. Thus, we suggest that at least 2 mechanisms are involved in IL
      12 regulation of angiogenesis, removing the pro-angiogenic stimulus and blocking
      the release and activity of MMPs.

PMID- 9766573
TI  - Suppression of Erk activation and in vivo growth in esophageal cancer cells by
      the dominant negative Ras mutant, N116Y.
AB  - Our previous studies demonstrated that introduction of a dominant negative H-ras
      mutant, N116Y, inhibits the growth of various types of cancer cells in vitro. In
      this study, we tested the efficacy of N116Y in blocking the growth of esophageal
      cancer cells using an adenoviral vector. Infection with N116Y adenovirus, (AdCMV
      N116Y), in which N116Y expression is driven by the cytomegalovirus promoter,
      significantly reduced the in vitro growth of all esophageal cancer cell lines
      studied. Esophageal cancer cells that contained wild-type K-ras and H-ras (TE8,
      SGF3, SGF7) were more sensitive to AdCMV-N116Y than HEC46 cells that expressed
      mutant K-ras protein. Most importantly, direct injection of AdCMV-N116Y into TE8-
      or SGF3-induced tumors in nude mice suppressed their growth significantly. To
      examine the suppressive mechanism of N116Y, cell cycle profile and the activation
      of extracellular signal-regulated kinase 2 (Erk2) were examined by flow cytometry
      and Western blot analysis, respectively. In TE8 cells, progression into S phase
      was clearly blocked after infection with AdCMV-N116Y. Infection with AdCMV-N116Y
      did not strongly suppress the activation of Erk2 after EGF stimulation in serum
      starved HEC46 cells, whereas it completely suppressed activation in TE8, SGF3 and
      SGF7 cells. Our observations suggest that N116Y reduces growth of human
      esophageal cancer cells and suppresses the activation of Erk2; they also indicate
      that N116Y is a potential candidate gene for human esophageal cancer gene
      therapy.

PMID- 9766574
TI  - Characterization of p53 mutants identified in human tumors with a missense
      mutation in the tetramerization domain.
AB  - p53 is very often mutated in human cancers. The majority of alterations are
      missense mutations located within the DNA-binding domain of the protein. Many
      reports have characterized such mutant proteins. Little is known, however, about
      the properties of proteins that have a missense mutation outside this domain. We
      investigated here the properties of 8 mutant proteins identified in human tumors
      as having a missense mutation in the tetramerization domain. The Arg342Gln,
      Glu349Asp and Gln354Arg proteins behaved like wild-type both in vitro and in
      cells. Two mutants, Arg342Pro and Leu344Pro, were inactive in all assays.
      Finally, the 3 mutant proteins Leu330His, Arg337Cys and Arg337Leu, which are
      inactive in vitro, showed no activity at low expression levels in cells but
      became active at higher expression levels. Our results reveal new phenotypes for
      p53 mutants and suggest that sequencing of the p53 gene from patients with tumors
      should be extended to exons 9 and 10 in clinical investigations.

PMID- 9766576
TI  - Does wheat bran or does wheat dietary fibre protect against breast cancer?

PMID- 9766575
TI  - Lonidamine as a modulator of taxol activity in human ovarian cancer cells:
      effects on cell cycle and induction of apoptosis.
AB  - The ability of lonidamine (LND), an energolytic derivative of indazole-carboxylic
      acid, to modulate the cytotoxicity of Taxol (TX) was investigated in the A2780
      human ovarian cancer cell line. Different cytotoxicity results were obtained as a
      function of treatment schedule. Specifically, TX followed by LND produced
      synergistic effects. Conversely, antagonistic effects were recorded when drugs
      were given simultaneously or according to the opposite sequence. TX induced an
      oligonucleosomal DNA fragmentation typical of the apoptotic process. The extent
      and the kinetics of DNA cleavage in samples treated with the taxane alone were
      similar to those of samples treated with the TX-LND sequence. Activation of Yama
      protease and degradation of poly (ADP-ribose) polymerase were not observed after
      individual or combined treatment. LND did not appreciably modify the effect
      exerted by TX on proteins involved in cell cycle progression (i.e., inhibition of
      p34cdc2 expression) and apoptosis (i.e., upregulation of wt p53 and
      transactivation of p21waf1), and only caused a slight induction of the Bax
      protein. LND alone did not affect tubulin polymerization in A2780 cells and, when
      administered after a 24 hr TX exposure, did not appreciably alter the extent of
      tubulin polymerization induced by the taxane. Although additional studies are
      needed to define the molecular basis of the TX-LND interaction, our results
      suggest that LND can positively modulate the antitumor activity of TX in ovarian
      cancer cells and indicate that the energolytic is potentially useful in
      combination therapy including the taxane in ovarian cancer patients.

PMID- 9766577
TI  - Expression of multiple cancer/testis (CT) antigens in breast cancer and melanoma:
      basis for polyvalent CT vaccine strategies.

PMID- 9766578
TI  - p53 antibodies in the saliva of patients with squamous cell carcinoma of the oral
      cavity.

PMID- 9766579
TI  - Matrix metalloproteinase-2 in blood does not indicate the progression of prostate
      cancer.

PMID- 9766580
TI  - Long-term survival from uterine cervical cancer in Mumbai (Bombay), India.

PMID- 9766581
TI  - Surgery for esophageal cancer in elderly patients: the view from Nottingham.
AB  - OBJECTIVE: Our aim was to compare the outcome of esophageal resection for
      carcinoma in elderly patients (aged over 70 and over 80 years) with that of
      younger patients managed within a single specialist thoracic surgery unit.
      PATIENTS AND METHODS: Between January 1987 and November 1997, 523 patients
      underwent esophagectomy for carcinoma in the Nottingham City Hospital Thoracic
      Surgery Unit. The patients were divided into 3 groups by age: group I, under 70
      years (n = 337); group II, 70 to 79 years (n = 150), and group III, 80 to 86
      years (n = 36). These groups were compared with regard to preoperative medical
      status, operability and resectability, complications, operative mortality, and
      longterm survival. RESULTS: Patients in groups II (6.0%) and III (2.8%) had fewer
      preexisting respiratory problems than patients in group I (12.5%), and the
      patients in group III had fewer preexisting cardiovascular problems (16.7%) than
      patients in groups I (25.2%) and II (32.7 %). Although patients in group III were
      generally less likely to have operable lesions (64.3%), no significant
      differences in resectability rate were detected among the 3 groups (80.8%, 77.7%,
      and 80%). Elderly patients (groups II and III) had a higher incidence of overall
      (34% and 36.1%), respiratory (24.7% and 19.4%), and cardiovascular (7.3% and
      11.1%) complications than those aged under 70 years (24.6%, 16.3%, and 2.1%,
      respectively). However, operative mortality (4.7%, 6.7%, and 5.6%) and 5-year
      survivals inclusive of operative mortality (25.1%, 21.2%, and 19.8%) were similar
      among the 3 groups. CONCLUSIONS: Accumulated experience in all aspects of
      perioperative management may account for a low hospital mortality in elderly
      patients despite a greater operative risk. The survival benefit is similar to
      that in the younger age groups, enforcing the view that esophagectomy within
      specialist thoracic units can be safely offered (in appropriately selected
      patients) with acceptable long-term survival in all age groups.

PMID- 9766582
TI  - Transesophageal biopsy of mediastinal and pulmonary tumors by means of endoscopic
      ultrasound guidance.
AB  - OBJECTIVE: The aim of this study was to investigate the value of endoscopic
      ultrasound-guided biopsy for the diagnosis of thoracic lesions. METHODS:
      Transesophageal ultrasound-guided biopsy was performed in 29 patients with
      mediastinal (n = 25) or pulmonary tumors (n = 4). A flexible echoendoscope with a
      7.5 MHz curved array transducer (Pentax FG 32 UA, Hamburg, Germany) and a biopsy
      device with a fine needle (diameter 0.8 mm) were used for all examinations. Three
      patients were excluded from the analysis of the data because a definite diagnosis
      based on surgery or follow-up was not available. RESULTS: Real-time visualization
      of the biopsy procedure with endoscopic ultrasound enabled accurate tissue
      sampling even of small mediastinal lesions with a diameter of less than 1 cm.
      Diagnostic material was obtained in 23 of the 26 patients (88%). In 3 cases (12%)
      non-representative biopsy material was found in the specimen. The sensitivity and
      specificity of transesophageal biopsy in the diagnosis of malignancy were 89% and
      83%, respectively. Histologic analysis of the biopsy specimens established
      malignancy in 17 of 23 patients, whereas benign lesions were diagnosed in 6
      patients. Endoscopic ultrasound-guided biopsy confirmed the diagnosis suggested
      by conventional diagnostic methods in 15 of 23 patients (65%), whereas an
      unsuspected diagnosis was disclosed in 8 patients (35%). The results of the
      biopsy had considerable impact on the therapeutic strategy. None of the patients
      had complications related to the procedure. CONCLUSIONS: Endoscopic ultrasound
      guided biopsy provides a new minimally invasive approach to the biopsy of lesions
      in the posterior mediastinum and may complement surgical staging procedures.

PMID- 9766583
TI  - Recurrent aortic coarctation: is surgical repair still the gold standard?
AB  - OBJECTIVE: We reviewed our experience with surgical repair compared with balloon
      aortoplasty of recurrent coarctations of the aorta. METHODS: This is a
      retrospective review of 1 institution's 27-year experience with surgical repair
      of recurrent aortic coarctation. A thorough chart review was performed of all
      pediatric patients undergoing surgical repair for recurrent aortic coarctation (n
      = 56) from January 1970 through July 1996. RESULTS: The vast majority of
      recoarctations were repaired with a prosthetic patch technique, with a greater
      than 96% success rate. No deaths or major complications occurred in the 56
      patients. Although a direct comparison with balloon aortoplasty cannot be done,
      we have reviewed the data available in the literature and found higher
      complication rates and lower success rates than we obtained in our series.
      CONCLUSIONS: Although the treatment of aortic coarctation has improved
      significantly during the past decades, persistent hypertension after repairs at
      an older age and recurrent coarctation after repairs in neonates occur in all
      institutions. Surgeons have not agreed on the optimal approach to primary
      coarctation repair, and invasive cardiologists have challenged operative
      intervention for both recurrent and primary coarctation. This study demonstrates
      that surgical repair of recurrent coarctation of the aorta can be performed
      safely and with excellent results. We believe it is still the gold standard in
      the management of recurrent coarctation of the aorta.

PMID- 9766584
TI  - The effect of ventricular volume reduction surgery in the dilated, poorly
      contractile left ventricle: a simple finite element analysis.
AB  - OBJECTIVES: Ventricular volume reduction surgery has been proposed by Batista to
      improve cardiac function in patients with dilated cardiomyopathy. However,
      limited clinical data exist to determine the efficacy of this operation. A finite
      element simulation is therefore used to determine the effect of volume reduction
      surgery on left ventricular end-systolic elastance, diastolic compliance, stroke
      work/end-diastolic volume (preload recruitable stroke work), and stroke work/end
      diastolic pressure (Starling) relationships. METHODS: End-diastole and end
      systole were represented by elastic finite element models with different unloaded
      shapes and nonlinear material properties. End-systolic elastance, diastolic
      compliance, preload recruitable stroke work, and Starling relationships, as well
      as energy expenditure per gram of unresected myocardium, were calculated. Two
      different types of volume reduction surgery (apical and lateral) were simulated
      at 10% and 20% left ventricular mass reduction. RESULTS: Ventricular volume
      reduction surgery causes diastolic compliance to shift further to the left on the
      pressure-volume diagram than end-systolic elastance. Volume reduction surgery
      increases the slope of the preload recruitable stroke work relationship (dilated
      cardiomyopathy 0.006 J/mL; 20% lateral volume reduction surgery 0.009 J/mL) but
      decreases the slope of the Starling relationship (dilated cardiomyopathy 0.028
      J/mm Hg; 20% lateral volume reduction 0.023 J/mm Hg). For a given amount of
      resection, lateral volume reduction has a greater effect than apical volume
      reduction. Ten-percent and 20% lateral volume reduction reduces energy
      expenditure by 7% and 17%, respectively. CONCLUSION: Ventricular volume reduction
      surgery shifts end-systolic elastance and diastolic compliance to the left on the
      pressure-volume diagram. The net effect on ventricular function is mixed. Volume
      reduction surgery increases the slope of preload recruitable stroke work, but
      increased diastolic compliance causes a small decrease in the Starling
      relationship (3 mm Hg difference between dilated cardiomyopathy and volume
      reduction surgery at stroke work = 0.5 J).

PMID- 9766585
TI  - Large encircling cryoablation without mapping for ventricular tachycardia after
      anterior myocardial infarction: long-term outcome.
AB  - OBJECTIVE: Map-guided procedures have been the accepted standard for ventricular
      tachycardia surgery. However, promising results of visually guided resections
      without mapping have been reported. The goal of this study was to evaluate the
      efficacy of large encircling cryoablation without mapping for ventricular
      tachycardia after anterior myocardial infarction. METHODS: Between 1985 and 1996,
      this procedure, along with aneurysmectomy, was performed on 38 patients for
      malignant ventricular tachycardia. The mean interval between the operation and
      myocardial infarction was 59.2 months; 7 patients (18.4%) were operated on within
      1 month of myocardial infarction. The mean patient age was 62.1 +/-7.3 years and
      the mean left ventricular ejection fraction was 29.0% +/-7.2%. RESULTS: Hospital
      mortality was 2.6% (1 patient). The electrical success rate based on
      postoperative electrophysiologic studies was 94.5%. Overall electrical success
      rate was 89.1%. Freedom from ventricular tachycardia was 77% (95% CI 61%-94%) at
      both 5 and 7 years. Freedom from sudden cardiac death was 91% (95% CI 80%-100%)
      at both 5 and 7 years, with overall actuarial survivals at 5 and 7 years of 63%
      (95% CI 47%-80%) and 42% (95% CI 22%-63%), respectively. The main cause of late
      death was congestive heart failure in 62.6% of these patients. CONCLUSIONS: One
      can achieve good results without intraoperative mapping in the treatment of
      patients with ventricular tachycardia after anterior myocardial infarction by
      using large encircling cryoablation.

PMID- 9766586
TI  - Preoperative risk models for minimally invasive coronary bypass: a preliminary
      study.
AB  - OBJECTIVE: Available risk assessment models are designed for standard coronary
      artery bypass grafting. We hypothesized that minimally invasive coronary bypass
      could improve on predicted outcome in extremely high-risk patients (Parsonnet
      score > 20%) by the current risk models. METHODS: From September 1996 to
      September 1997, 27 consecutive extremely high-risk patients underwent minimally
      invasive coronary bypass. Seventeen patients were male; age was 73 +/- 12 years,
      and 63% of patients were older than 75 years. Left ventricular ejection fraction
      was 33.7% +/- 15% and 63% had an ejection fraction of less than 35%. The
      predicted 30-day mortality according to the System 97 model was 25.6% +/- 11.3%.
      The Parsonnet risk score was 36.2% +/- 11%; the predicted length of stay in the
      hospital was 15.3 +/- 3 days. The predicted risk of stroke according to the
      Multicenter Perioperative Stroke Risk Index was 22.3% +/- 11.7%. RESULTS:
      Minimally invasive coronary bypass was isolated in 20 patients and integrated
      with angioplasty and stenting in 7 patients. The observed 30-day mortality was 0%
      (P < .01 vs predicted): at an average follow-up of 10.8 +/- 4.1 months, 26
      patients (96.3%) are alive without angina; one patient with acquired
      immunodeficiency syndrome died on postoperative day 40 of acute pancreatitis. No
      patient had a stroke or neurologic deficit (P < .01 vs predicted). Patency of
      internal thoracic artery anastomosis was confirmed by angiography in all 27
      patients. No patient required reoperation. Eighteen patients (67%) were extubated
      in the operating room. The observed length of hospital stay after minimally
      invasive coronary bypass was 3.8 +/- 2.6 days (P < .01 vs predicted). CONCLUSION:
      On the basis of our results on a relatively small series of patients, we suggest
      that risk models geared for standard coronary bypass grafting may not be
      appropriate for minimally invasive coronary bypass.

PMID- 9766587
TI  - Regression of left ventricular hypertrophy after aortic valve replacement for
      aortic stenosis with different valve substitutes.
AB  - OBJECTIVE: Stentless biologic aortic valves are less obstructive than stented
      biologic or mechanical valves. Their superior hemodynamic performances are
      expected to reflect in better regression of left ventricular hypertrophy. We
      compared the regression of left ventricular hypertrophy in 3 groups of patients
      undergoing aortic valve replacement for severe aortic stenosis. Group I (10
      patients) received stentless biologic aortic valves, group II (10 patients)
      received stented biologic aortic valves, and group III (10 patients) received
      bileaflet mechanical aortic valves. METHODS: Echocardiographic evaluations were
      performed before the operation and after 1 year, and the results were compared
      with those of a control group. Left ventricular diameters and function, left
      ventricular wall thickness, and left ventricular mass were assessed by
      echocardiography. RESULTS: Group I patients had a significantly lower maximum and
      mean transprosthetic gradient than the other valve groups (P = .001). One year
      after operation there was a significant reduction in left ventricular mass for
      all patient groups (P < .01), but mass did not reach normal values (P = .05).
      Although the rate of regression in the interventricular septum and posterior wall
      thickness differed slightly among groups, their values at follow-up were
      comparable and still higher than control values (P = .002). The ratio between
      interventricular septum and posterior wall and the ratio between wall thickness
      and chamber radius did not change significantly at follow-up. CONCLUSIONS:
      Because the number of patients was relatively small, we could not use left
      ventricular mass regression after I year to distinguish among patients undergoing
      aortic valve replacement for aortic stenosis by means of valve prostheses with
      different hemodynamic performances.

PMID- 9766588
TI  - Long-term Doppler echocardiographic results of aortic or mitral valve replacement
      with Biocor porcine bioprosthesis.
AB  - OBJECTIVES: Our objectives were to evaluate the long-term bioprosthetic and
      cardiac functional outcome after insertion (over a 10-year period) of a new
      generation porcine zero pressure-fixed Biocor bioprosthesis, as well as to
      determine the echocardiographic accuracy for selection of patients requiring
      reoperation. The long-term systematic Doppler echocardiographic assessment after
      valve replacement with this bioprosthesis is lacking. METHODS: Between January
      1983 and January 1993, we inserted 756 Biocor prostheses in the aortic (619) or
      mitral (137) positions. All 51 patients who had a reoperation during the follow
      up time were evaluated echocardiographically before reoperation. Additionally,
      263 of 446 patients (59%) with aortic bioprostheses and 42 of 74 patients (57%)
      with mitral bioprostheses who were alive in January 1993 had long-term
      echocardiographic follow-up. RESULTS: Group A: Normally functioning bioprostheses
      were found in the aortic position in 242 of 263 patients and in the mitral
      position in 33 of 42 patients. Group B: Thirty patients had abnormal
      bioprosthetic function. Eleven patients had regurgitation, 3 had a combined
      lesion, and signs of calcification appeared in 16 patients with aortic valves,
      all with a peak gradient of above 60 mm Hg. Group C: Patients who had a
      reoperation (41 aortic and 10 mitral) within the follow-up period were followed
      up echocardiographically from the detection of a possible valve dysfunction until
      reoperation, and the findings accorded well with those at operation in 49 of 51
      patients. CONCLUSIONS: These findings suggest that, during a long-term follow-up,
      most bioprostheses function normally, facilitating improved heart function.
      Abnormalities in a bioprosthesis usually develop gradually, enabling their
      detection by Doppler echocardiographic evaluations performed regularly or in case
      of any symptomatic deterioration.

PMID- 9766589
TI  - Cardiac valve endothelial cells: relevance in the long-term function of biologic
      valve prostheses.
AB  - OBJECTIVE: For reasons that are still unclear, biologic heart valve prostheses
      undergo degeneration after implantation. We studied the possible role of the
      immune system in this process. METHODS: We examined the expression of
      immunologically relevant molecules by human cardiac valve endothelium in situ and
      in vitro and studied re-endothelialization of implanted allogeneic and xenogeneic
      valvular surfaces using explanted bioprostheses and valves obtained from donor
      hearts at cardiac retransplantation. RESULTS: We demonstrate that human cardiac
      valve endothelial cells express molecules capable of initiating immune responses
      and might therefore play a role in the degeneration of viable cardiac valve
      prostheses. Also, we show evidence of re-endothelialization on the surfaces of
      xenografts and allografts but not on valves obtained from previously transplanted
      hearts. CONCLUSION: Inasmuch as valves from previously transplanted hearts seem
      to be free from degeneration, we conclude that reduction of the immunogenicity of
      allograft valve prostheses by HLA matching or immunosuppressive treatment might
      further improve long-term results after allograft valve replacement.

PMID- 9766590
TI  - Adenovirus infection in the lung results in graft failure after lung
      transplantation.
AB  - OBJECTIVES: Our goal was to examine the relationship between viral pneumonia and
      outcome in pediatric patients undergoing lung or heart-lung transplantation.
      METHODS: Prospective surveillance for common respiratory viruses of childhood was
      performed in all patients undergoing lung or heart-lung transplantation.
      Specimens were examined for the presence of replicating virus (by culture), viral
      genome (by polymerase chain reaction), and viral antigen (by immunofluorescence
      and immunohistochemical staining). The relationship between viral infection and
      outcome was examined. RESULTS: Sixteen patients underwent 19 transplants during
      the study period, with follow-up of 1 to 26 months. Virus was identified in the
      transplanted lung in 29 instances; adenovirus was identified most commonly (8/16
      patients) and had the greatest impact on outcome. In 2 patients with early,
      fulminant infection, adenovirus was also identified in the donor. Adenovirus was
      significantly associated with respiratory failure leading to death or graft loss
      and with the histologic diagnosis of obliterative bronchiolitis (P < or = .002 in
      each case). CONCLUSIONS: Adenovirus infection in the transplanted lung is
      significantly associated with graft failure, histologic obliterative
      bronchiolitis, and death. Health care personnel and families must be vigilant in
      preventing exposure of transplant recipients to this virus. Availability of a
      rapid and reliable test for adenovirus in donors and recipients would have an
      impact on management and could improve outcome for pediatric lung recipients.

PMID- 9766591
TI  - Epithelial regeneration and preservation of tracheal cartilage after tracheal
      replacement with cryopreserved allograft in the rat.
AB  - OBJECTIVE: We investigated the origin of the epithelium in transplanted
      cryopreserved tracheal allografts in rats and tried to clarify the mechanism by
      which immunogenicity is reduced in this procedure. METHODS: Tracheal
      transplantation was performed with PVG rats (allele at the RT1 locus: c) used as
      donors and ACI rats (allele at the RT1 locus: a) as recipients. After resection
      of a 5-ring segment of the cervical trachea of an ACI rat, the trachea was
      reconstructed with the cryopreserved tracheal segment of a PVG rat (n = 6). No
      immunosuppressive agents or steroids were given. Histologic changes were
      determined and immunohistochemical staining was performed to investigate major
      histocompatibility complex class I antigens of the transplanted tracheal segment.
      RESULTS: Two months after tracheal transplantation, 6 surviving ACI rats were
      killed. Histologically, the epithelium and tracheal cartilage of the transplanted
      cryopreserved segment displayed normal structure. Immunohistochemical staining
      showed that the major histocompatibility complex class I antigen of the ACI rat
      was expressed in the epithelium of the transplanted segment and that the class I
      antigen of the PVG rat was expressed in the cartilage of the transplanted
      segment. CONCLUSIONS: After transplantation of the cryopreserved trachea, the
      epithelium of the transplanted cryopreserved segment originated from the
      recipient epithelium whereas the cartilage retained the structure of the donor
      trachea. We hypothesize that transplantation of a cryopreserved trachea leads to
      the growth of the recipient's epithelium over the donor trachea, thereby reducing
      the antigenicity of the transplant.

PMID- 9766592
TI  - A prospective comparison of atrio-femoral and femoro-atrial flow in adult
      venovenous extracorporeal life support.
AB  - INTRODUCTION: In the United States, venovenous extracorporeal life support has
      traditionally been performed with atrial drainage and femoral reinfusion (atrio
      femoral flow). Although flow reversal (femoro-atrial flow) may alter
      recirculation and extracorporeal flow, no direct comparison of these 2 modes has
      been undertaken. OBJECTIVE: Our goal was to prospectively compare atrio-femoral
      and femoro-atrial flow in adult venovenous extracorporeal life support for
      respiratory failure. METHODS: A modified bridge enabling conversion between atrio
      femoral and femoro-atrial flow was incorporated in the extracorporeal circuit.
      Bypass was initiated in the direction that provided the highest pulmonary
      arterial mixed venous oxygen saturation, and the following measurements were
      taken: (1) maximum extracorporeal flow, (2) highest achievable pulmonary arterial
      mixed venous oxygen saturation, and (3) flow required to maintain the same
      pulmonary arterial mixed venous oxygen saturation in both directions. Flow
      direction was then reversed, and the measurements were repeated. Data were
      compared with paired t tests and are presented as mean +/- standard deviation.
      RESULTS: Ten patients were studied, and 9 were included in the data analysis.
      Femoro-atrial bypass provided (1) higher maximal extracorporeal flow (femoro
      atrial flow = 55.6 +/- 9.8 mL/kg per minute, atrio-femoral flow = 51.1 +/- 11.1
      mL/kg per minute; P = .04) and (2) higher pulmonary arterial mixed venous oxygen
      saturation (femoroatrial flow = 89.9% +/- 6.6%, atrio-femoral flow = 83.2% +/-
      4.2%; P = .006); (3) furthermore, it required less flow to maintain an equivalent
      pulmonary arterial mixed venous oxygen saturation (femoro-atrial flow = 37.0 +/-
      12.2 mL/kg per minute, atrio-femoral flow = 46.4 +/- 8.8 mL/kg per minute; P =
      .04). CONCLUSIONS: During venovenous extracorporeal life support, femoro-atrial
      bypass provided higher maximal extracorporeal flow, higher pulmonary arterial
      mixed venous oxygen saturation, and required comparatively less flow to maintain
      an equivalent mixed venous oxygen saturation than did atrio-femoral bypass.

PMID- 9766593
TI  - Importance of preoperative liver function as a predictor of survival in patients
      supported with Thoratec ventricular assist devices as a bridge to
      transplantation.
AB  - Patient selection is crucial for the success of ventricular assist devices as a
      bridge to heart transplantation. PURPOSE: The objective of this study was to
      identify preoperative markers for survival and end-organ recovery in patients
      having a ventricular assist device. METHODS: A retrospective study was performed
      on 32 severely ill patients with end-stage cardiac failure being mechanically
      bridged to heart transplantation with the Thoratec Ventricular Assist Device
      System (Thoratec Laboratories Corporation, Pleasanton, Calif) in a single center
      between 1984 and 1995. The preoperative cardiac index averaged 1.6 L/min per
      square meter with a pulmonary capillary wedge pressure of 29 mm Hg. Because of a
      high incidence of hepatic or renal dysfunction, or both (total bilirubin: 3.5 +/-
      6.2 mg/dL; creatinine: 2.0 +/- 1.3 mg/dL), biventricular support was used in most
      patients (28/32). A total of 30 preoperative and 4 perioperative variables were
      evaluated for their association with survival and liver recovery. RESULTS:
      Nineteen patients (59.4%) survived to transplantation and 13 died. All 19
      patients undergoing transplantation were discharged alive with a 1-year survival
      of 94.4%. All patients without liver recovery died of multiorgan failure. Direct
      and indirect bilirubin measurements were the only significant predictors for
      survival to discharge (P = .036, .045); all other factors failed to show
      significance. As direct bilirubin levels increased (normal range, 3 times normal,
      and >3 times normal), patient survival decreased (82 %, 56%, and 33 %,
      respectively). In addition, bilirubin and liver enzyme levels before insertion of
      the assist device were significantly associated with liver recovery during
      support with the device. CONCLUSION: In our patient population with ventricular
      assist devices, liver function is the most predictive factor of patient survival
      in bridging to transplantation.

PMID- 9766594
TI  - Platelet-rich plasmapheresis in cardiac surgery: a meta-analysis of the effect on
      transfusion requirements.
AB  - OBJECTIVE: Our purpose was to determine whether intraoperative platelet-rich
      plasmapheresis in cardiac surgery is effective in reducing the proportion of
      patients exposed to allogeneic red cell transfusions. METHODS: A systematic
      search for prospective, randomized trials of platelet-rich plasmapheresis in
      cardiac surgery, using MEDLINE, HEALTHSTAR, Current Contents, "Biological
      Abstracts," and EMBASE/Excerpta Medica up to August 1997, was completed. Trials
      were included if they reported either the proportion of patients exposed to
      allogeneic red cells or the units of allogeneic red cells transfused. Trials were
      abstracted by 2 independent investigators and the quality of trial design was
      assessed with the use of a validated scale. RESULTS: Seventeen references met the
      inclusion criteria (1369 patients [675 control: 694 platelet-rich
      plasmapheresis]). Platelet-rich plasmapheresis reduced the likelihood of exposure
      to allogeneic red cells in cardiac surgery (odds ratio 0.44; 95% confidence
      interval 0.27, 0.72, P = .001). Platelet-rich plasmapheresis had a small but
      statistically significant effect on both the volume of blood lost in the first 24
      hours (weighted mean difference -102 mL; 95% confidence interval -148, -55 mL, P
      < .0001) and the mean units transfused (weighted mean difference -0.33 units; 95%
      confidence interval -0.43, -0.23, P < .0001). However, platelet-rich
      plasmapheresis was only marginally effective (odds ratio 0.83, 95% confidence
      interval 0.34, 2.01, P = .68) for "good" quality trials, whereas it appeared very
      effective in trials with poor methodologic quality (odds ratio 0.33, 95%
      confidence interval 0.17, 0.62, P = .0007). CONCLUSIONS: Although platelet-rich
      plasmapheresis appeared effective in decreasing the proportion of patients
      receiving transfusions after cardiac operations, the quality of most of the
      supporting trials was low and the benefit was small in trials of good quality.
      Further clinical trials should be completed.

PMID- 9766595
TI  - Successful bilobectomy for pulmonary venous obstruction after bilateral lung
      transplantation.

PMID- 9766596
TI  - Aggressive surgery for treating a pulmonary metastasis of a benign giant cell
      tumor of the bone: results in four cases.

PMID- 9766597
TI  - Is complete systematic nodal dissection by thoracoscopic surgery possible? A
      prospective trial of video-assisted lobectomy for cancer of the right lung.

PMID- 9766598
TI  - Paraplegia after surgery of the thoracic esophagus.

PMID- 9766599
TI  - Rhadbdomyolysis after coronary artery bypass grafting in a patient receiving
      simvastatin.

PMID- 9766600
TI  - Myxoma of right femoral vein origin presenting as a right atrial mass with
      syncope.

PMID- 9766601
TI  - Coarctation of the aorta with right aortic arch and isolation of the left
      innominate artery: a surgical challenge in a patient without collateral posterior
      brain circulation.

PMID- 9766602
TI  - Rupture of the ascending aorta in Ehlers-Danlos syndrome after surgical repair of
      multiple arteriovenous malformations with the use of cardiopulmonary bypass.

PMID- 9766603
TI  - Cerebral venous thrombosis after the Fontan procedure.

PMID- 9766604
TI  - Modification of anterior approach to superior sulcus tumors.

PMID- 9766605
TI  - Leiomyosarcoma of the pulmonary veins extending into the left atrium or left
      atrial leiomyosarcoma: multimodality therapy.

PMID- 9766606
TI  - The addition of saphenous vein graft to the left anterior descending artery in
      left internal thoracic artery hypoperfusion syndrome.

PMID- 9766607
TI  - Use of ultracision harmonic scalpel for isolation of intramyocardial coronary
      vessels during coronary revascularization of the beating heart.

PMID- 9766608
TI  - Axillary artery-coronary artery bypass grafting in patients with atherosclerotic
      ascending aorta.

PMID- 9766609
TI  - Can you top this?

PMID- 9766610
TI  - Delayed iatrogenic aortic dissection from coronary bypass.

PMID- 9766611
TI  - Fiftieth anniversary of the insertion of an artificial heart valve.

PMID- 9766612
TI  - Historical perspectives of the American Association for Thoracic Surgery. Ethan
      Flagg Butler (1884-1964).

PMID- 9766613
TI  - Measuring outcome in schizophrenia: differences among the atypical
      antipsychotics. Collaborative Working Group on Clinical Trial Evaluations.
AB  - The advent of the atypical antipsychotics marked a new era in the history of the
      treatment of psychotic disorders. To evaluate the published literature about the
      available atypical antipsychotics--clozapine, risperidone, olanzapine, and
      quetiapine--and select the most appropriate treatment for specific patients,
      physicians need to understand the outcome measures used in clinical studies, the
      pharmacologic differences that explain varying side effect profiles, and
      pharmacoeconomic assessments that are used in the decision-making process. While
      the atypical antipsychotics have established efficacy in the overall treatment of
      schizophrenia, they may differ in their effects on factors such as cognitive
      function, overall quality of life, adverse events, and hospitalization status.
      Each of these factors should be considered when weighing treatment options for an
      individual patient.

PMID- 9766614
TI  - Clinical development of atypical antipsychotics: research design and evaluation.
      Collaborative Working Group on Clinical Trial Evaluations.
AB  - Clinical trials support the efficacy and safety of new drugs on the market. They
      provide the United States Food and Drug Administration with the information
      needed to approve an Investigational New Drug application and are the basis for
      package inserts provided by the manufacturers that guide clinicians in the use of
      a new drug. Because clinical trials are vital to the effective and safe use of
      new drugs, it is important to understand who participates in them, what questions
      are answered by clinical trials, and what questions are raised. The reader who
      asks the proper questions about issues such as methodology, affiliations of the
      investigators, statistical analyses performed, location of study centers, and
      study populations will derive the most information from the report of a clinical
      trial.

PMID- 9766615
TI  - Adverse effects of the atypical antipsychotics. Collaborative Working Group on
      Clinical Trial Evaluations.
AB  - Adverse effects of antipsychotics often lead to noncompliance. Thus, clinicians
      should address patients' concerns about adverse effects and attempt to choose
      medications that will improve their patients' quality of life as well as overall
      health. The side effect profiles of the atypical antipsychotics are more
      advantageous than those of the conventional neuroleptics. Conventional agents are
      associated with unwanted central nervous system effects, including extrapyramidal
      symptoms (EPS), tardive dyskinesia, sedation, and possible impairment of some
      cognitive measures, as well as cardiac effects, orthostatic hypotension, hepatic
      changes, anticholinergic side effects, sexual dysfunction, and weight gain. The
      newer atypical agents have a lower risk of EPS, but are associated in varying
      degrees with sedation, cardiovascular effects, anticholinergic effects, weight
      gain, sexual dysfunction, hepatic effects, lowered seizure threshold (primarily
      clozapine), and agranulocytosis (clozapine only). Since the incidence and
      severity of specific adverse effects differ among the various atypicals, the
      clinician should carefully consider which side effects are most likely to lead to
      the individual's dissatisfaction and noncompliance before choosing an
      antipsychotic for a particular patient.

PMID- 9766616
TI  - Assessment of EPS and tardive dyskinesia in clinical trials. Collaborative
      Working Group on Clinical Trial Evaluations.
AB  - The incidence of acute extrapyramidal symptoms (EPS)--akathisia, dystonia, and
      parkinsonism--associated with traditional antipsychotics varies, but most
      researchers agree that neuroleptic-induced EPS occur in 50% to 75% of patients
      who take conventional antipsychotics. Atypical antipsychotics were developed to
      widen the therapeutic index and to reduce EPS. Although the mechanisms are
      unclear, the risk of EPS is less with the novel antipsychotics than with
      conventional drugs, and agents that produce low levels of acute EPS are likely to
      produce less tardive dyskinesia. Nevertheless, clinicians should exercise caution
      when comparing data from investigations of the novel antipsychotics and, until
      long-term data become available, should administer the new drugs at doses below
      the EPS-producing level.

PMID- 9766617
TI  - Assessing the effects of atypical antipsychotics on negative symptoms.
      Collaborative Working Group on Clinical Trial Evaluations.
AB  - Attempts to clarify the domains of schizophrenia gained importance when the
      atypical antipsychotics joined the armamentarium of schizophrenia treatments
      because of evidence that these agents are superior to conventional antipsychotics
      for the treatment of negative symptoms. Negative symptoms can be divided into 3
      components: (1) deficit or primary enduring negative symptoms that may or may not
      respond to treatment, (2) primary nonenduring negative symptoms, and (3)
      secondary negative symptoms that are associated with positive symptoms,
      extrapyramidal symptoms, depression, and environmental deprivation. The atypical
      antipsychotics have generally been found to be more effective than conventional
      antipsychotics against the totality of negative symptoms, but their effects on
      specific components are still under study. Sophisticated statistical tools such
      as path analysis have been used in investigations of the direct and indirect
      effects of atypical antipsychotics on negative symptoms, but these tools have
      limitations. Future study is needed to identify specific components of negative
      symptoms that may respond preferentially to one or another of the atypical
      antipsychotics.

PMID- 9766618
TI  - Evaluating the effects of antipsychotics on cognition in schizophrenia.
      Collaborative Working Group on Clinical Trial Evaluations.
AB  - Cognitive deficits are an integral feature of schizophrenia and have a
      deleterious effect on the ability of schizophrenic patients to work and function
      in a social environment. Drugs that bring about substantial cognitive improvement
      represent a major contribution in improving the quality of life in schizophrenia.
      Recent studies have suggested that the atypical antipsychotics may be more useful
      than conventional agents for improving cognition. There is evidence that scores
      on neuropsychological assessments have improved after treatment with clozapine,
      risperidone, and quetiapine. Future research is needed to characterize and
      quantify the cognitive effects of the atypical antipsychotics.

PMID- 9766619
TI  - Atypical antipsychotics for treatment of depression in schizophrenia and
      affective disorders. Collaborative Working Group on Clinical Trial Evaluations.
AB  - Depression in schizophrenia may be partially responsible for the increased
      suicide rate in schizophrenic patients, which is more than 20 times higher than
      that found in the general population. Affective disorders in patients with
      schizophrenia are associated with a poor outcome, an increased risk of relapse,
      and a high rate of suicide. There is evidence that atypical antipsychotics may
      contribute to a reduction in suicidality, and although the new drugs are marketed
      for the treatment of schizophrenia, their novel psychopharmacologic effects
      suggest the possibility of other therapeutic applications. Recent studies of the
      efficacy of the novel antipsychotics found that these agents may produce an
      antidepressant effect in schizophrenia and may be used as either an adjunctive
      medication or an alternative to mood stabilizers in patients with affective
      disorders.

PMID- 9766620
TI  - Treatment of special populations with the atypical antipsychotics. Collaborative
      Working Group on Clinical Trial Evaluations.
AB  - Atypical antipsychotics have become the treatment of choice for patients
      experiencing a first episode of schizophrenia. In addition, they are often
      prescribed for conditions such as bipolar disorder and dementia. While clinical
      trials have not yet established the efficacy of the atypical antipsychotics for
      these uses, a number of reports offer preliminary evidence that the atypical
      antipsychotics may be beneficial for affective disorders, substance abuse
      disorder, senile dementia, and pathologic aggression. Atypical agents may be
      particularly effective and tolerable in elderly patients who are especially
      susceptible to the adverse effects of conventional antipsychotic medication.
      Lower dosages are more necessary for the elderly than for younger adults. Current
      evidence suggests that clozapine is the most effective atypical antipsychotic for
      neuroleptic-resistant patients. Risperidone, olanzapine, and quetiapine may also
      be effective in a subset of these patients.

PMID- 9766621
TI  - Adoptive immunotherapy of cancer using monocyte-derived macrophages: rationale,
      current status, and perspectives.
AB  - Adoptive transfer of host defense cells may be able to correct an otherwise
      defective generation of competent immune cells in patients with cancer. Ex vivo
      grown cytotoxic macrophages (MAC) able to recognize and destroy tumor cells but
      not normal cells are effective in murine models of metastasizing tumors. After
      the development of large-scale technology to generate MAC in vitro from blood
      monocytes (MO), clinical trials in cancer patients have proven the feasibility
      and safety of infusing >3 x 10(9) autologous MO-derived MAC activated by
      interferon-gamma or lipopolysaccharide. Various modalities of adoptive
      immunotherapy with human MAC have been realized: routes of application used were
      intravenous, intraperitoneal, intrapleural, and through selective hepatic artery
      perfusion. In addition, MAC have been generated from MO collected after granulyte
      macrophage colony-stimulating factor treatment in vivo. Biodistribution studies
      using 111indium-labeled cells have revealed localization of MAC to sites of bulk
      tumor growth on regional infusion as well as to liver metastases on systemic
      application. Malignant ascites disappeared in about 50% of patients after
      intraperitoneal treatment, yet no other evidence of therapeutic efficacy of MAC
      could be demonstrated. Further advances of adoptive transfer of MO-derived cells
      are developed with emphasis on the generation of antigen-presenting cells primed
      in vitro with tumor cells or specific peptides.

PMID- 9766622
TI  - Nitric oxide synthase inhibition reduces muscle inflammation and necrosis in
      modified muscle use.
AB  - The objective of this study was to determine the role of nitric oxide in muscle
      inflammation, fiber necrosis, and apoptosis of inflammatory cells in vivo. The
      effects of nitric oxide synthase (NOS) inhibition on the concentrations of
      neutrophils, ED1+ and ED2+ macrophages, apoptotic inflammatory cells, and
      necrotic muscle fibers in rats subjected to 10 days of hindlimb unloading and 2
      days of reloading were determined. Administration of NOS inhibitor N(omega)-nitro
      L-arginine methyl ester (L-NAME) significantly reduced the concentrations of
      neutrophils, ED1+ and ED2+ macrophages, and necrotic fibers in soleus muscle
      relative to water-treated controls. The concentration of apoptotic inflammatory
      cells was also significantly lower for L-NAME-treated animals compared with water
      treated controls. However, the proportion of the inflammatory cell population
      that was apoptotic did not differ between L-NAME-treated and control animals,
      suggesting that L-NAME treatment did not decrease inflammatory cell populations
      by increasing the frequency of apoptosis. Thus, nitric oxide or one of its
      intermediates promotes muscle inflammation and fiber necrosis during modified
      muscle use and plays no more than a minor role in the resolution of muscle
      inflammation by inducing apoptosis of inflammatory cells.

PMID- 9766623
TI  - Leukocyte trafficking in experimental autoimmune uveitis in vivo.
AB  - Leukocyte trafficking from blood into tissue is a fundamental process in immune
      surveillance and the immune response to stimuli. Experimental autoimmune uveitis
      (EAU) is an animal model for posterior uveitis and is mediated by T lymphocytes
      and macrophages that infiltrate the posterior segment of the eye. To analyze
      leukocyte migration into retinal tissue during the course of EAU, labeled cells
      were identified in vivo by scanning laser ophthalmoscopy and in retinal
      flatmounts by confocal microscopy. Adhesion of blood leukocytes to retinal
      endothelial cells in vivo was significantly raised 48 h before the appearance of
      clinical disease, and this correlated with the increased expression of CD54 on
      retinal vessels. Mitogen-activated spleen cells and CD4+ T cells only entered
      into retinal tissue in animals with clinical disease and not naive recipients.
      The disease status of the donor animal had no effect on leukocyte trafficking.
      These results, which identify leukocyte-endothelial cell interactions in vivo,
      suggest that the activation of the retinal endothelium is a prerequisite to
      leukocyte adhesion and extravasation into ocular tissue during EAU.

PMID- 9766625
TI  - Nitric oxide enhances the growth of U937 human leukemic cells through a
      cyclooxygenase-mediated pathway.
AB  - The mechanisms of exogenous nitric oxide (NO)-enhanced growth of the U937 human
      myeloid leukemic cells were examined using sodium nitroprusside (SNP) as a NO
      donor. Treatment with 0.1 mM SNP for 72 h caused a 45 +/- 2% increase in U937
      cell growth with significantly increased S/G2+M-phase and decreased G0/G1-phase
      of the cell cycle. The growth-enhancing effect of SNP was blocked by
      indomethacin, a cyclooxygenase inhibitor, but not by H7, a broad spectrum kinase
      inhibitor, or PD98059, a mitogen-activated protein kinase inhibitor. SNP
      treatment resulted in a dose-dependent increase in prostaglandin E2 (PGE2)
      production. Furthermore, the addition of exogenous PGE2 not only enhanced U937
      cell growth but restored the indomethacin-inhibited mitogenic effect of SNP. We
      suggest that NO can enhance cell growth through activating the cyclooxygenase
      pathway and that PGE2 may be an effector molecule for NO-regulated cell
      proliferation. Our data provide a mechanistic insight into the regulatory role of
      NO in myelopoiesis.

PMID- 9766624
TI  - Genetic and immunological parameters governing in vivo susceptibility/resistance
      to retrovirally induced murine malignant histiocytosis.
AB  - Malignant histiocytosis sarcoma virus (MHSV) arose as a recombinant of c-Harvey
      ras murine sarcoma virus (Ha-MuSV) and Friend mink cell focus-forming virus (F
      MCFV). It is a defective acute transforming retrovirus that, along with Friend
      murine leukemia helper virus (F-MuLV), induces malignant histiocytosis (MH) in
      susceptible adult mice. We have assessed the in vivo susceptibility to MHSV in
      inbred homozygous, F1 hybrid, congenic, and recombinant inbred (RI) mice. We have
      shown that: (1) in vivo resistance to MHSV is multigenic, regulated by MHC and
      non-MHC genes in a different fashion than with F-MCFV, F-MuLV, or Ha-MuSV; (2)
      using BXD RI mice, the resistance phenotype is linked with 95.8% probability to
      two linked loci, Pmv-9 and Iapls3-14, on chromosome 13 (homologous to the area of
      human chromosome 5 for which a chromosomal break point at position 5q35 is
      associated with human MH); and (3) CD4+ T cells are critical for MHSV resistance.

PMID- 9766626
TI  - Ionizing radiation potentiates the induction of nitric oxide synthase by IFN
      gamma and/or LPS in murine macrophage cell lines: role of TNF-alpha.
AB  - Macrophages are activated to become cytotoxic by a highly coordinated set of
      cytokine signals. Ionizing radiation can mimic cytokine signals and lead to
      enhanced states of activation. We tested the ability of gamma-radiation, alone
      and with interferon-gamma (IFN-gamma) and/or lipopolysaccharide (LPS), to induce
      nitric oxide (NO) production in J774.1 and RAW264.7 murine macrophages. NO was
      induced weakly, moderately, or strongly by IFN-gamma alone, LPS alone, or IFN
      gamma + LPS, respectively. Radiation alone (0.5-50 Gy) did not induce NO, but
      enhanced NO production in a dose-dependent manner (0.5-5 Gy) when cells were
      exposed to IFN-gamma or LPS 24 h post-irradiation. Immunoblots showed parallel
      induction of nitric oxide synthase (NOS2). Application of anti-tumor necrosis
      factor alpha (TNF-alpha) antibody before irradiation blocked induction of NO by
      IFN-gamma. We conclude (1) that irradiated cells produce more NO in response to
      either IFN-gamma or LPS and (2) that the increase is mediated by induction of TNF
      alpha.

PMID- 9766627
TI  - P-selectin and MAC-1 mediate monocyte rolling and adhesion to ECM-bound platelets
      under flow conditions.
AB  - Accumulation of monocyte-derived foam cells in focal areas of the atherosclerotic
      (A.S.-) lesion is one of the key events in early atherogenesis. Using a flow
      model for the damaged vessel wall, we examined the ability of ECM-bound platelets
      to induce monocyte tethering and adhesion. Whereas ECM-proteins alone induced
      monocyte adhesion only at low shear stresses (< 100 mPa), ECM-bound platelets
      induced monocyte rolling and adhesion at shear stresses up to 240 mPa. Studies
      with specific antibodies showed that monocyte adhesion to platelets was mainly
      mediated by P-selectin and monocyte PSGL-1 (maximum inhibition 90%). beta2
      Integrin blocking CD18 and CD11b antibodies partly inhibited the arrest of
      rolling cells. Antibodies against other adhesion molecules such as LFA-1, PECAM
      1, and beta1-integrins had no effect. Even sparsely adhered platelets
      (approximately 10% coverage of the surface) already strongly supported monocyte
      tethering. In conclusion, activated platelets present on ECM are a powerful
      adhesive substrate for monocyte recruitment under flow conditions.

PMID- 9766628
TI  - The identification and characterization of umbilical cord blood-derived human
      basophils.
AB  - Cross-linking allergen-specific immunoglobin E on human peripheral blood
      basophils results in the release of histamine and other inflammatory mediators
      that initiate allergy and asthma. The signaling pathways leading from IgE binding
      to mediator release have not been well established, mainly due to the difficulty
      in obtaining adequate numbers of highly purified basophils. It was the goal of
      this study to easily obtain Fc epsilonRI-positive human basophils in high yield
      and purity for studies of signal transduction pathways. We describe an in vitro
      culture system in which pulsing normal human cord blood leukocytes with
      interleukin-3 (IL-3) for 3-4 h followed by incubation in medium with fetal bovine
      serum generates a cell population that is predominately Fc epsilonRI positive
      between 14 and 28 days of culture. These cells resemble peripheral blood
      basophils when examined by light and electron microscopy. Like normal blood
      basophils, they express the integrins, CD11b, CD18, CD29, and CD49d. A majority
      of the IL-3-pulsed cells also express a marker recognized by the basophil
      specific antibody, 2D7. Fc epsilonRI cross-linking results in a time and dose
      dependent release of histamine. Fc epsilonRI cross-linking also stimulates
      protein-tyrosine phosphorylation, thought to be the first event leading to the
      IgE-mediated activation of peripheral blood basophils. These studies establish
      cord blood as an accessible source from which basophil-like cells can be
      developed to examine Fc epsilonRI-mediated signal transduction.

PMID- 9766629
TI  - Monocyte-derived dendritic cells have a phenotype comparable to that of dermal
      dendritic cells and display ultrastructural granules distinct from Birbeck
      granules.
AB  - Most monocyte-derived dendritic cells (DC) display CD1a, like Langerhans cells
      (LC) and some dermal DC, but their relationship with these skin DC remains
      unclear. To address this issue, we studied the expression of different antigens
      characteristic of skin DC and of monocyte/macrophages in CD1a+ and CD1a- monocyte
      derived DC. Their phenotype indicated that they may be related to dermal DC
      rather than to LC, i.e., they were all CD11b-positive, and 72% were Factor XIIIa
      positive, but they did not express E-cadherin nor VLA-6. It is interesting that
      CD1a+ and CD1a-cells showed intracytoplasmic granules that were different from LC
      Birbeck granules. These phenotypical and ultrastructural features are comparable
      to those of CD14-derived DC obtained from cord blood precursors [C. Caux et al.
      J. Exp. Med. 184, 695-706]. These results show a close relationship between these
      two in vitro models, which are both related to dermal DC.

PMID- 9766630
TI  - The murine neutrophil-chemoattractant chemokines LIX, KC, and MIP-2 have distinct
      induction kinetics, tissue distributions, and tissue-specific sensitivities to
      glucocorticoid regulation in endotoxemia.
AB  - Lipopolysaccharide-induced CXC chemokine (LIX) is a novel murine neutrophil
      chemoattractant CXC chemokine cloned as a glucocorticoid-attenuated response
      gene. We investigated LIX message expression in an acute endotoxemia model. LIX
      message peaks later than KC or macrophage inflammatory protein-2 (MIP-2) and
      remains elevated longer in almost all tissues. Induced LIX message expression in
      heart is 5- to 6-fold greater than in lung and spleen, and 20-fold greater than
      in liver. In contrast, KC expression is equal in heart, lung, and liver, whereas
      MIP-2 expression is strongest in the lung. Glucocorticoid regulation of these
      genes also differs. Endotoxemia-induced LIX message expression in the lung is
      markedly enhanced in adrenalectomized mice and strongly attenuated by
      dexamethasone, whereas lung KC and MIP-2 expression are unaffected by
      glucocorticoids. It is surprising to note that endotoxemia-induced brain
      expression of LIX (but not KC or MIP-2) is increased by dexamethasone. These
      observations suggest that LIX may have biological roles distinct from KC and MIP
      2.

PMID- 9766631
TI  - Strong expression of CD134 (OX40), a member of the TNF receptor family, in a T
      helper 2-type cytokine environment.
AB  - CD134 (OX40) is involved in T cell costimulation and T cell-dependent antibody
      production. We show strongly increased T cell expression of CD134 in a model of T
      helper 2-mediated systemic autoimmunity, induced by HgCl2. Regulation of CD134
      expression on CD4+ T cells was further studied in vitro, identifying CD134 as an
      early marker of T cell activation. CD134 expression could be induced by
      interleukin-4, but not by interferon-gamma or tumor necrosis factor-alpha.
      Effects of interleukin-4 and of phorbol 12-myristate 13-acetate on CD134
      expression could be blocked by the protein kinase inhibitor staurosporin.
      Combination of these stimuli with ionomycin resulted in a strongly synergistic
      increase of CD134 expression, which was blocked by the calcineurin-inhibitor
      cyclosporin A. The results demonstrate the involvement of two synergistically
      acting pathways in induction of CD134 expression. Furthermore, they suggest a
      role for interleukin-4 in induction of CD134 expression in vivo.

PMID- 9766632
TI  - Interleukin-8 priming of human neutrophils is not associated with persistently
      altered calcium fluxes but is additive with lipopolysaccharide.
AB  - Interleukin-8 (IL-8) priming was studied in neutrophils to examine its dependency
      on altered calcium fluxes and for similarity to lipopolysaccharide (LPS). IL-8
      caused a rapid rise in [Ca2+]i that returned to baseline values by 20 min. Peak
      [Ca2+]i transients in response to N-formyl-methionyl-leucyl-phenylalanine (fMLP)
      were unaltered in IL-8-primed compared with unprimed cells. In comparison to LPS
      and tumor necrosis factor (TNF), IL-8 was a much weaker priming agent as measured
      by either O2- or H2O2 production. Despite their large disparity in potency, IL-8
      and LPS printing were additive using fMLP, a receptor-dependent stimulator, and
      synergistic using the post-receptor, protein kinase C activator, phorbol 12
      myristate 13-acetate (PMA) to trigger the respiratory burst. In contrast, IL-8
      and TNF priming were synergistic for fMLP (P = 0.05), but completely nonadditive
      when PMA was used as the neutrophil stimulant (P = 0.05 for subadditivity). Thus,
      lasting alterations in [Ca2+]i are not a necessary characteristic of IL-8-primed
      cells. IL-8 and LPS appear to prime by non-overlapping pathways, whereas IL-8 and
      TNF appear to share mechanisms distal to protein kinase C activation. IL-8 and
      LPS may independently contribute to neutrophil-mediated host defense or injury by
      priming through distinct pathways.

PMID- 9766633
TI  - Interleukin-18/interferon-gamma-inducing factor, a novel cytokine, up-regulates
      ICAM-1 (CD54) expression in KG-1 cells.
AB  - Intercellular adhesion molecule-1 (ICAM-1, CD54) is a membrane glycoprotein and a
      member of the immunoglobulin superfamily. It plays a central role in cell to cell
      mediated immune responses and is a ligand for leukocyte function-associated
      antigen-1 (LFA-1). We report here that a newly discovered cytokine, interferon
      gamma-inducing factor (IGIF) [H. Okamura et al. (1995) Nature 378, 88] recently
      proposed to be designated as IL-18, selectively up-regulates ICAM-1 expression in
      KG-1 cells, a human myelomonocytic cell line, in which IL-18 also enhances
      interferon-gamma production. IL-18 induced heterotypic aggregation between KG-1
      and Peer T cells, which was blocked by anti-ICAM-1 and/or LFA-1 antibodies. Anti
      interferon-gamma antibody did not block the IL-18-induced up-regulation of ICAM-1
      on KG-1 cells. These results thus show that IGIF/IL-18, enhances ICAM-1
      expression in KG-1 cells in an interferon-gamma-independent pathway, up-regulates
      ICAM-1 functions, and that IL-18 might play a potential role in immunoregulation
      by mediating immune cell infiltration into the tissues.

PMID- 9766634
TI  - TNF and IL-6 mediate MIP-1alpha expression in bleomycin-induced lung injury.
AB  - Previously, macrophage inflammatory protein-1alpha (MIP-1alpha), a member of the
      C-C chemokine family, has been implicated in bleomycin-induced pulmonary
      fibrosis, a model of the human disease idiopathic pulmonary fibrosis.
      Neutralization of MIP-1alpha protein with anti-MIP-1alpha antibodies
      significantly attenuated both mononuclear phagocyte recruitment and pulmonary
      fibrosis in bleomycin-challenged CBA/J mice. However, the specific stimuli for
      MIP-1alpha expression in the bleomycin-induced lesion have not been
      characterized. In this report, two mediators of the inflammatory response to
      bleomycin, tumor necrosis factor (TNF) and interleukin-6 (IL-6), were evaluated
      as putative stimuli for MIP-1alpha expression after bleomycin challenge in CBA/J
      mice. Elevated levels of bioactive TNF and IL-6 were detected in bronchoalveolar
      lavage (BAL) fluid and lung homogenates from bleomycin-treated CBA/J mice at time
      points post-bleomycin challenge, which precede MIP-1alpha protein expression.
      Treatment of bleomycin-challenged mice with soluble TNF receptor (sTNFr) or anti
      IL-6 antibodies significantly decreased MIP-1alpha protein expression in the
      lungs. Furthermore, normal alveolar macrophages secreted elevated levels of MIP
      1alpha protein in response to treatment with TNF plus IL-6 or bleomycin plus IL
      6, but not TNF, bleomycin, or IL-6 alone. Finally, leukocytes recovered from the
      BAL fluid of bleomycin-challenged mice secreted higher levels of MIP-1alpha
      protein, compared to controls, when treated with TNF alone. Based on the data
      presented here, we propose that TNF and IL-6 are part of a cytokine network that
      modulates MIP-1alpha protein expression in the profibrotic inflammatory lesion
      during the response to intratracheal bleomycin challenge.

PMID- 9766635
TI  - Activation of mitogen-activated protein kinase cascades during priming of human
      neutrophils by TNF-alpha and GM-CSF.
AB  - The signal transduction pathways activated by tumor necrosis factor alpha (TNF
      alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF) that lead to
      priming of polymorphonuclear leukocytes (PMNs) are unknown. The hypotheses that
      these cytokines stimulate multiple mitogen-activated protein kinase (MAPK)
      cascades, including extracellular signal-regulated kinases (ERKs), c-Jun amino
      terminal kinases (JNKs), and p38 MAPK, and that these MAPKs participate in
      priming of human PMNs were examined. TNF-alpha stimulated a dose-dependent
      increase in ERK and p38 MAPK activities that was maximal at 10 min. JNKs were not
      stimulated by TNF-alpha or GM-CSF. GM-CSF stimulated ERK activity comparable to
      that of TNF-alpha, but GM-CSF was a less potent stimulus of p38 MAPK activity.
      The tyrosine kinase inhibitor, genistein, inhibited ERK and p38 MAPK stimulation
      by both cytokines. The phosphatidylinositol 3-kinase inhibitor, wortmannin,
      attenuated stimulation of ERKs and p38 MAPK by GM-CSF, but not TNF-alpha. GM-CSF,
      but not TNF-alpha, stimulated wortmannin-sensitive activation of Raf-1. TNF-alpha
      and GM-CSF priming of superoxide release stimulated by N-formyl-methionyl-leucyl
      phenylalanine was significantly attenuated by the MEK inhibitor, PD098059, and
      the p38 MAPK inhibitor, SB203580. Incubation with both MAPK inhibitors produced
      an additive effect. Our data suggest that TNF-alpha and GM-CSF activate ERKs and
      p38 MAPK by different signal transduction pathways. Both ERK and p38 MAPK
      cascades contribute to the ability of TNF-alpha and GM-CSF to prime the
      respiratory burst response in human PMNs.

PMID- 9766636
TI  - The IFN-inducible nucleoprotein IFI 16 is expressed in cells of the monocyte
      lineage, but is rapidly and markedly down-regulated in other myeloid precursor
      populations.
AB  - IFI 16 is an interferon-inducible nucleoprotein expressed by human monocytes. IFI
      16 and a related mouse protein, p202, control cellular proliferation by binding
      and modulating the functions of cell cycle regulatory factors including p53 and
      the retinoblastoma gene product, pRb. In this study, we examined IFI 16
      expression in myeloid precursor cells cultured in vitro in colony-forming assays
      using granulocyte (G-) and granulocyte-macrophage (GM-) colony-stimulating factor
      (CSF). IFI 16 was expressed in 100% of CD34+ cells isolated from human bone
      marrow. When the CD34+ cells were induced to differentiate, two sub-populations
      of cells were identified by two-color cytofluorography: the CD14+ (monocytoid)
      cells all expressed IFI 16, whereas the CD14- (polymorphonuclear precursor) cells
      did not. The strongest expression of IFI 16 was in the cells staining brightest
      for CD14, whereas depletion of CD14+ monocytoid cells from mixed
      monocytic/granulocytic cultures largely abolished IFI 16-stained cells.
      Furthermore, in eight independent colony-forming assays, the number of IFI 16+
      cells correlated closely with the numbers of monocyte precursors identified
      morphologically (R2 = 0.99), but was unrelated to the numbers of myelocytes,
      promyelocytes, and metamyelocytes; nor was IFI 16 expressed by erythroid or
      eosinophil precursors. We conclude that IFI 16 is expressed in CD34+ and
      monocytoid daughter cells, but is rapidly and markedly down-regulated at the
      corresponding stages of polymorphonuclear and erythroid development. This
      differential expression of IFI 16 in myeloid precursor subpopulations and its
      perceived molecular properties are consistent with a possible role in regulating
      myelopoiesis.

PMID- 9766638
TI  - Pathways for eosinophil lipid body induction: differing signal transduction in
      cells from normal and hypereosinophilic subjects.
AB  - Although lipid bodies, inducible cytoplasmic inclusions active in arachidonic
      acid metabolism, are abundant in activated leukocytes, including eosinophils,
      mechanisms for eosinophil lipid body formation are not certain. Eosinophils from
      hypereosinophilic syndrome (HES) donors contained about twice (approximately
      18/cell) as many lipid bodies as eosinophils froin normal donors (approximately
      10/cell). By immunocytochemistry both 5- and 15-lipoxygenases were localized at
      lipid bodies in HES eosinophils. Platelet-activating factor (PAF) induced rapid,
      receptor-mediated increases in lipid bodies in normal and HES eosinophils.
      Protein kinase C (PKC) inhibitors, chelerythrine and calphostin C, inhibited PAF
      induced lipid body formation partially in normal and HES eosinophils. In HES, but
      not normal, eosinophils, PAF-induced lipid body formation was completely blocked
      by two tyrosine kinase inhibitors, herbimycin A and genistein, which were not
      acting on 5-lipoxygenase because they also blocked 5-HETE-induced lipid body
      formation in HES, and not normal, eosinophils. After 24 h culture with eosinophil
      growth factor cytokines [interleukin (IL)-3, IL-5, and granulocyte-macrophage
      colony-stimulating factor (GM-CSF) or GM-CSF alone but not IL-5 or IL-3 alone],
      normal eosinophils were induced to exhibit an HES-like phenotype, including
      increased lipid body numbers and tyrosine kinase-dependent signaling for PAF
      induced lipid body formation. Thus, signal transduction mechanisms involved in
      PAF-induced lipid body formation in eosinophils can be differentially recruited.
      Tyrosine kinase-dependent signaling is not involved in normal eosinophils, but is
      active in HES eosinophils and in normal eosinophils cultured with GM-CSF. PKC-
      and tyrosine kinase-dependent pathways are involved in the formation of
      eosinophil lipid bodies, which may facilitate enhanced synthesis of lipoxygenase
      derived eicosanoids.

PMID- 9766639
TI  - Translational research: walking the bridge between idea and cure--seventeenth
      Bruce F. Cain Memorial Award lecture.
AB  - Advances in the understanding of normal and malignant cell biology are allowing
      the development of biologically targeted drugs directed at specific differences
      between host and tumor. The array of potential new targets is vast, but drugs
      currently in development are targeted at cell-cycle regulators, growth factors
      and their receptors, signal transduction intermediates, angiogenesis, and the
      mechanisms that mediate apoptosis and DNA repair. Recent results raise the
      possibility that novel biologically targeted agents, perhaps in combination with
      traditional cytotoxic agents, may finally cure cancer. However, the development
      of a biologically targeted drug raises unique challenges in the design of
      clinical trials to demonstrate its efficacy, and despite the promising
      preclinical data that exist for most of the agents in development, the clinical
      trial remains the critical, final step across the bridge from basic research to
      clinical application. In this review, we discuss some of the challenges in the
      clinical development of biologically targeted agents and the implications for
      clinical trial design.

PMID- 9766637
TI  - Role of the mitogen-activated protein kinases and tyrosine kinases during
      leukotriene B4-induced eosinophil activation.
AB  - Exposure of guinea-pig eosinophils to leukotriene B4 (LTB4; 1 microM) resulted in
      a rapid generation of H2O2 (index of NADPH oxidase activation), stimulated
      [3H]arachidonic acid (AA) release (index of phospholipase A2 activity), and
      promoted CD18-dependent homotypic aggregation. Under similar conditions, LTB4 (1
      microM) induced a rapid activation of extracellular-regulated kinases-1 and 2
      (ERK-1/2) but not c-jun N-terminal kinases 46 and 54 (JNK-46/54) or p38 mitogen
      activated protein kinase (p38 MAP kinase). To examine the role of ERK-1/2 in the
      mechanism of eosinophil activation, a selective inhibitor of MAP kinase kinase
      1/2 (MEK-1/2), PD098059, was employed. However, PD 098059 at concentrations that
      attenuated ERK-1/2 activation had no significant affect on eosinophil activation.
      In contrast, a role for tyrosine kinases in LTB4-induced eosinophil activation
      was suggested by studies with the tyrosine kinase inhibitors, herbimycin A and
      lavendustin A. However, the results of those experiments implied divergent
      pathways for the control of eosinophil responses because the inhibitors were more
      effective at attenuating H2O2 generation than [3H]AA release, and had little
      effect on homotypic aggregation.

PMID- 9766640
TI  - Widespread skeletal metastatic potential of human lung cancer revealed by green
      fluorescent protein expression.
AB  - To understand the skeletal metastatic pattern of non-small cell lung cancer, we
      developed a stable high-expression green fluorescent protein (GFP) transductant
      of human lung cancer cell line H460 (H460-GFP). The GFP-expressing lung cancer
      was visualized to metastasize widely throughout the skeleton when implanted
      orthotopically in nude mice. H460 was transduced with the pLEIN retroviral
      expression vector containing the enhanced GFP and the neomycin (G418) resistance
      gene. A stable high GFP-expressing clone was selected in vitro using 800
      microg/ml G418. Stable high-level expression of GFP was maintained in s.c.
      growing tumors formed after injecting H460-GFP cells in nude mice. To use H460
      GFP for visualization of metastasis, fragments of s.c.-growing H460-GFP tumors
      were implanted by surgical orthotopic implantation in the left lung of nude mice.
      Subsequent micrometastases were visualized by GFP fluorescence in the
      contralateral lung, plural membrane, and widely throughout the skeletal system
      including the skull, vertebra, femur, tibia, pelvis, and bone marrow of the femur
      and tibia. The use of GFP-expressing H460 cells transplanted by surgical
      orthotopic implantation revealed the extensive metastatic potential of lung
      cancer in particular to widely disseminated sites throughout the skeleton. This
      new metastatic model can play a critical role in the study of the mechanism of
      skeletal and other metastasis in lung cancer and in screening of therapeutics
      that prevent or reverse this process.

PMID- 9766641
TI  - Loss of chromosome 18q is an early event in pancreatic ductal tumorigenesis.
AB  - Cytogenetic and molecular studies demonstrated that pancreatic cancer frequently
      shows specific chromosomal abnormalities, such as losses of 9p, 17p, and 18q, and
      gains of 8q and 20q. We have analyzed alterations in the copy number of specific
      chromosomal regions in cells from the pancreatic juices of 32 patients with
      various pancreatic disorders by fluorescence in situ hybridization (FISH)
      technique to pursue the possible clinical use of early diagnosis of pancreatic
      cancer. None of the chromosomal abnormalities were found in 13 specimens from
      individuals who had no neoplastic lesions. On the other hand, 12 specimens (63%)
      derived from the remaining 19 patients who had neoplastic lesions showed at least
      one chromosomal abnormality. Ten of these specimens were from pancreatic cancer
      patients; 7 cases (70%) showed chromosomal abnormalities. All but one of the 12
      tumors with chromosomal abnormalities had loss of 18q. Furthermore, we detected a
      tumor in one patient in whom the routine cytological method and endoscopic
      retrograde chorangiopancreatography found nothing. Based on the results by FISH,
      we performed endoscopic ultrasonography and found a small serous cystadenoma in
      this patient. These results indicate that: (a) FISH analysis of cells from
      pancreatic juices obtained during endoscopic retrograde chorangiopancreatography
      is quite useful for detecting pancreatic ductal tumors; and (b) loss of
      chromosome 18q is one of the early genetic changes that provide very useful
      information in diagnosing pancreatic neoplasias.

PMID- 9766642
TI  - Mutational analysis of the transforming growth factor beta receptor type II gene
      in human ovarian carcinoma.
AB  - In the present study, we evaluated a series of sporadic ovarian carcinomas for
      mutations within the entire coding region of TbetaR-II. Using reverse
      transcription-PCR and "Cold" single-strand conformational polymorphism analysis,
      6 of 24 samples (25%) were found to contain code-altering mutations in TbetaR-II:
      (a) four mutations resulting in amino acid substitutions in the highly conserved
      serine/threonine kinase domain; (b) one mutation resulting in a conservative
      amino acid change in the transmembrane domain; and (c) a 1-bp insertion in the
      polyadenylic acid microsatellite region resulting in a reading frameshift. In
      addition, six cases (25%) exhibited a common bp substitution (C-->T at nucleotide
      1322) in both tumor and patient-matched normal tissues. This is the first report
      of such TbetaR-II mutations in primary human ovarian carcinomas.
      Immunohistochemical analysis demonstrated a loss of expression of TbetaR-II in 5
      of 22 available tumors (23%; 4 of which also had mutations in the coding region)
      and decreased expression of TbetaR-II in 10 of 22 available tumors (44%; 1 of
      which had a mutation in the coding region). Thus, the loss or decreased
      expression of TbetaR-II seems to be a common event in sporadic ovarian
      carcinomas, and mutational inactivation, due to either frameshift mutations in
      the polyadenylic acid microsatellite region or point mutations in conserved
      functional domains, is one mechanism by which this occurs.

PMID- 9766643
TI  - A novel candidate oncogene, MCT-1, is involved in cell cycle progression.
AB  - Using the arbitrarily primed-PCR (AP-PCR) assay to detect genetic abnormalities
      that occur in a panel of lymphoid cell lines, we identified an amplified stretch
      of genomic DNA that contained a putative open reading frame. Northern blot
      analysis with this genomic clone revealed widespread low level expression in
      normal human tissue. The full cDNA sequence was obtained with no significant
      homology to any known genes in the genome database. We termed this novel gene
      with multiple copies in a T-cell malignancy as MCT-1. MCT-1 was localized to the
      long arm of chromosome Xq22-24 by flourescence in situ hybridization analysis.
      Although there was no significant homology at the primary sequence level, there
      was a limited degree of amino acid homology with a domain of cyclin H that
      appears to specify protein-protein complexes. This relationship between MCT-1 and
      cyclin H implied a potential role for MCT-1 in cell cycle regulation.
      Overexpression of MCT-1 increased the proliferative rate of cells by decreasing
      the length of the G1 phase without a reciprocal increase in the S and G2-M
      phases. Recent work has established the role of cell cycle regulatory molecules
      in the development of certain human malignancies. Therefore, we investigated the
      transforming ability of MCT-1 overexpression using soft agar growth assays and
      demonstrated that only MCT-1-overexpressing cells were able to establish
      colonies. Taken together, MCT-1 is a novel candidate oncogene with homology to a
      protein-protein binding domain of cyclin H.

PMID- 9766645
TI  - NS398, a selective cyclooxygenase-2 inhibitor, induces apoptosis and down
      regulates bcl-2 expression in LNCaP cells.
AB  - Cyclooxygenase (COX)-2, an inducible enzyme that catalyzes the formation of
      prostaglandins and other eicosanoids from arachidonic acid, is constitutively
      expressed in LNCaP human prostate cancer cell line. To evaluate the potential
      role of COX-2 in prostate cancer, LNCaP cells were treated with NS398, a
      selective COX-2 inhibitor, and the effects on cell viability and apoptosis were
      determined. NS398 treatment induced apoptosis in LNCaP cells in a time- and dose
      dependent fashion. Treatment with 100 microM NS398 caused a down-regulation in
      bcl-2 protein expression, followed by chromatin condensation, chromosomal DNA
      fragmentation, and changes in nuclear morphology detected by 4,6-diamidino-2
      phenylindole staining, DNA fragmentation assay, and terminal deoxynucleotidyl
      transferase-mediated UTP-biotin nick end-labeling assay. In contrast, NS398
      treatment had no effect on either cell viability or nuclear function and
      morphology in human fetal prostate fibroblasts. These results demonstrate that
      NS398 induces apoptosis in LNCaP cells but not in human fetal prostate
      fibroblasts, and that this induction is associated with a decreased level of bcl
      2 protein.

PMID- 9766644
TI  - RIZ1, but not the alternative RIZ2 product of the same gene, is underexpressed in
      breast cancer, and forced RIZ1 expression causes G2-M cell cycle arrest and/or
      apoptosis.
AB  - The retinoblastoma protein-interacting zinc finger gene RIZ maps to the distal
      short arm of human chromosome 1 (1p36), a region thought to harbor tumor
      suppressor genes for a variety of human cancers including breast cancer. The RIZ
      gene normally produces two protein products of different length, RIZ1 and RIZ2.
      RIZ2 is generated by an internal promoter and lacks an NH2-terminal motif of
      RIZ1, the PR domain conserved in a subfamily of zinc finger genes that function
      as negative regulators of tumorigenesis. We have here studied whether the RIZ
      gene may play a role in human neoplasia. We found that expression of RIZ1 is
      commonly decreased or at undetectable levels in breast cancer tissues and cell
      lines. Decreased RIZ1 expression was also found in other tumor types including
      neuroblastoma and lung cancer. Remarkably, RIZ2 is normally expressed in all
      cases examined, suggesting that the abnormality observed for RIZ1 is specific.
      Forced RIZ1 expression in breast cancer cells caused cell cycle arrest in G2-M
      and/or programmed cell death. These observations suggest an exclusive negative
      selection for RIZ1 but not RIZ2 in breast cancer and a role for RIZ1 in tumor
      suppression.

PMID- 9766647
TI  - Development of Helicobacter pylori-induced gastric carcinoma in Mongolian
      gerbils.
AB  - Helicobacter pylori is classified by IARC/WHO as a definite human gastric
      carcinogen, despite "inadequate experimental evidence." To obtain direct evidence
      concerning this relationship, we investigated the histopathological findings of
      gastric mucosa using a model of H. pylori infection in Mongolian gerbils. The
      animals were challenged p.o. with H. pylori ATCC-43504 and sacrificed at 6, 12,
      and 18 months after inoculation for histological examination. All inoculated
      animals were infected with H. pylori. Severe infiltration of the lamina propria
      by polymorphonuclear and mononuclear cells appeared in the lesser curvature of
      the antrum, with an increase in epithelial cell proliferation, and the
      infiltration extended to the body. Atrophic gastritis and focal intestinal
      metaplasia also appeared in the lesser curvature of the antral mucosa at 6 months
      after inoculation. Intestinal metaplasia became severe, with dysplasia, after
      that. At 18 months after H. pylori inoculation, two of five infected animals
      showed three well-differentiated gastric cancers. The uninfected control animals
      showed no abnormal findings throughout the entire observation period. Here, it
      was confirmed that H. pylori infection alone causes gastric cancer in an animal
      model.

PMID- 9766646
TI  - Enhanced expression of the insulin receptor substrate-2 docking protein in human
      pancreatic cancer.
AB  - Insulin receptor substrate-2 (IRS-2) is a multisite docking protein implicated in
      mitogenic signaling after activation of the insulin and insulin-like growth
      factor (IGF)-I receptors. In the present study, we characterized IRS-2 expression
      and function in human pancreatic cancer. IRS-2 mRNA and protein were expressed in
      ASPC-1 and COLO-357 human pancreatic cancer cell lines. Insulin, IGF-I, and IGF
      II enhanced the growth of both cell lines, stimulated tyrosine phosphorylation of
      IRS-2, and increased IRS-2-associated phosphatidylinositol (PI) 3-kinase
      activity. The mitogenic effects of insulin, IGF-I, and IGF-II were markedly
      attenuated by the PI 3-kinase inhibitor LY 294002. Northern blot analysis of
      total RNA extracted from normal and cancerous tissues revealed that IRS-2 mRNA
      levels were increased in the cancer tissues (P = 0.032). In the normal pancreas,
      IRS-2 immunoreactivity was present at low levels in some ductal and acinar cells
      and at moderate levels in a heterogeneous pattern in all of the endocrine islets.
      In the pancreatic cancers, IRS-2 was abundant in the ductal-like cancer cells.
      These findings indicate that IRS-2 is overexpressed in human pancreatic cancer
      and suggest that it may contribute to enhanced mitogenic signaling via the PI 3
      kinase pathway, thereby leading to excessive growth stimulation in this
      malignancy.

PMID- 9766648
TI  - Chromosomal amplification is associated with cisplatin resistance of human male
      germ cell tumors.
AB  - Chemotherapy resistance of tumors is an important biological and clinical
      problem. Studies from many tumor types have indicated that resistance may be
      based on multiple genetic pathways. Human male germa cell tumors (GCTs) are an
      especially good model system to study the genetic basis of tumor sensitivity and
      resistance to chemotherapy. GCTs are exquisitely sensitive to treatment with DNA
      damaging drugs such as cisplatin, rarely exhibit TP53 gene mutations, express
      normal p53 protein, and undergo p53-mediated apoptosis upon drug treatment. A
      small proportion of tumors (20-30% of metastatic lesions) escape the apoptotic
      response and result in treatment resistance. We have recently shown (J.
      Houldsworth, et al., Oncogene, 16: 2345-2359, 1998) that in a subset of such
      tumors, resistance is linked to TP53 gene mutations. In a further search for
      genetic mechanisms underlying resistance, we subjected a panel of 17 tumors from
      relapse-free patients (sensitive) and 17 chemotherapy-resistant tumors to
      comparative genomic hybridization analysis to identify possible amplified regions
      (implying amplified/overexpressed genes) associated with resistance. With the
      exception of 12p11.2-12, high level amplification was not detected in any of the
      sensitive tumors. We have identified eight amplified regions (1q31-32, 2p23-24,
      7q21, 7q31, 9q22, 9q32-34, 15q23-24, and 20q11.2-12) in five resistant tumors,
      which suggests that chromosomal and, hence, gene amplification may comprise a
      pathway to drug resistance. Identification of amplified/overexpressed genes at
      these sites may elucidate new genetic pathways of chemotherapy resistance in GCTs
      and possibly also in other tumors.

PMID- 9766649
TI  - The estrogen receptor variant lacking exon 5 has dominant negative activity in
      the human breast epithelial cell line HMT-3522S1.
AB  - The estrogen receptor variant lacking exon 5 (ERdeltaE5) encodes a truncated
      protein that lacks the hormone-binding domain and has been suggested to be
      responsible for the estrogen-independent growth of human breast tumors and
      resistance to antiestrogen therapy. The biological function of the ERdeltaE5 in
      human breast epithelial cells has been studied by transient transfection of HMT
      3522S1 cells with wild-type (wt) estrogen receptor (ER) and ERdeltaE5. A 10-fold
      higher expression of ERdeltaE5 mRNA compared to that of wt ER mRNA was found.
      However, the expression of ERdeltaE5 protein was significantly lower than the
      expression of wt ER protein. The ERdeltaE5 was unable to activate the
      transcription of an estrogen-responsive reporter gene in the absence as well as
      in the presence of estrogen. The ERdeltaE5 disclosed a dominant negative activity
      when expressed together with wt ER. These data indicate that the biological
      significance of ERdeltaE5 in human breast cancer is dubious.

PMID- 9766650
TI  - NUP98-HOXD13 gene fusion in therapy-related acute myelogenous leukemia.
AB  - A novel chromosomal translocation, t(2;11)(q31;p15), was identified in a patient
      with therapy-related acute myelogenous leukemia (t-AML). Fluorescence in situ
      hybridization experiments mapped the breakpoint near NUP98; Southern blot
      analysis demonstrated that the nucleoporin gene NUP98 was disrupted by this
      translocation. We used rapid amplification of cDNA ends to identify a chimeric
      mRNA. An in-frame, chimeric mRNA that fused NUP98 sequences to the homeobox gene
      HOXD13 was cloned; the predicted fusion protein contains both the GLFG repeats
      from NUP98 as well as the homeodomain from HOXD13. The NUP98-HOXD13 fusion is
      structurally similar to the NUP98-HOXA9 fusion previously identified in patients
      with AML, leading to the speculation that NUP98-homeobox gene fusions may be
      oncogenic. Moreover, this report, along with a recent study that demonstrated
      NUP98-DDX10 fusions in patients with t-AML, raises the possibility that NUP98 may
      be a previously unsuspected target for chromosomal translocations in patients
      with t-AML.

PMID- 9766651
TI  - Genomic alterations in fallopian tube carcinoma: comparison to serous uterine and
      ovarian carcinomas reveals similarity suggesting likeness in molecular
      pathogenesis.
AB  - Serous carcinomas of the fallopian tube, uterus, and ovary resemble each other
      both histologically and in clinical behavior. Comparative genomic hybridization
      was performed on 20 primary fallopian tube carcinoma specimens to find regions of
      the genome involved in tubal carcinogenesis and to compare the genomic
      alterations with those previously detected in serous ovarian and uterine
      carcinomas. The most frequent changes detected in fallopian tube carcinoma were
      gains at 3q (70%) and 8q (75%), with high-level amplifications in several cases.
      Other common gains occurred at 1q, 5p, 7q, 12p, and 20q. The most frequent losses
      were found at 18q, 8p, 4q, and 5q. The frequency and the pattern of chromosomal
      changes detected in tubal carcinoma were strikingly similar to those observed in
      serous ovarian and uterine carcinomas, suggesting common molecular pathogenesis.

PMID- 9766652
TI  - p53 is involved in but not required for ionizing radiation-induced caspase-3
      activation and apoptosis in human lymphoblast cell lines.
AB  - The caspase-3 has been shown to be involved in mediating apoptosis induced by
      different stimuli. However, it is still unclear whether p53 is required for the
      ionizing radiation (IR)-induced caspase-3 activation. In the present study, we
      examined IR-induced apoptosis in three closely related human lymphoblast cell
      lines that differ in p53 status. Irradiation of TK6 cells (wild-type p53) with 4
      Gy gamma-rays resulted in rapid apoptosis, whereas the apoptotic response was
      delayed and reduced in WTK1 cells (mutant p53) and the TK6 derivative line
      expressing HPV16 E6 (abrogated p53). The differential apoptotic responses in
      these cell lines correlated with caspase-3 activation. IR induced an early as
      well as a late phase of caspase-3 activation in TK6 but only a delayed onset in
      WTK1 and TK6-E6-5E cells. The early phase of caspase-3 activation coincided with
      an elevation of p53 and bax protein levels. Pretreatment of all three cell lines
      with a caspases inhibitor z-VAD-FMK inhibited apoptosis. These results suggest
      that IR-induced apoptosis is mediated by a mechanism involving the caspase-3
      cascade, which is shared by both p53-dependent and -independent pathways. The
      activation of caspase-3 by IR may thus engage at least two separate mechanisms,
      one through the regulation of the bcl-2 family members by p53, whereas the other
      yet-to-be-identified one involves neither p53 nor bax.

PMID- 9766653
TI  - Tumor suppressor proteins as regulators of cell differentiation.
AB  - The products of the tumor suppressor genes are considered to function as specific
      inhibitors of tumor cell growth. In this communication, we present evidence to
      show that these proteins inhibit tumor cell proliferation by participating in the
      activation of tumor cell differentiation. The ML-1 human myeloblastic leukemia
      cells used in this study proliferate when treated with insulin-like growth factor
      I and transferrin but differentiate to monocytes when exposed to tumor necrosis
      factor alpha or transforming growth factor beta1, or to macrophage-like cells
      when treated with both these cytokines. Initiation of proliferation but not of
      differentiation was followed by a 20- to 25-fold increase in the nuclear level of
      the DNA polymerase-associated processivity factor PCNA and of the proliferation
      specific transcription factor E2F1. In contrast, induction of differentiation but
      not of proliferation was followed by a 25- to 30-fold increase in the nuclear
      level of the tumor suppressor proteins p53 (wild type), pRb, and p130/Rb2 and of
      the p53-dependent cyclin kinase inhibitor p21/Cip1. p53 and p21/Cip1,
      respectively, inhibit the expression and activation of PCNA, whereas p130 and
      pRb, respectively, inhibit the expression and activation of E2F1. As a result, G1
      S-associated DNA and mRNA synthesis is inhibited, growth uncoupled from
      differentiation, and maturation enabled to proceed. Where this function of the
      tumor suppressor proteins is impaired, the capacity for differentiation is lost,
      which leads to the sustained proliferation that is characteristic of the cancer
      cell.

PMID- 9766654
TI  - Neuropeptides induce Mr 92,000 type IV collagenase (matrix metalloprotease-9)
      activity in human prostate cancer cell lines.
AB  - The type IV collagenases matrix metalloprotease (MMP)-2 and MMP-9 are linked with
      a wide array of biological activities, including tumor invasion, metastasis, and
      angiogenesis. Here, we report that neuropeptide hormones, which are present in
      prostatic adenocarcinomas, can stimulate secreted activity of MMP-9 in human
      prostate cancer cell lines. Northern blotting analyses demonstrated that
      neuropeptide stimulation lead to elevated mRNA levels of MMP-9 but not MMP-2.
      Further assays of MMP-9 promoter activation and a nuclear run-off indicated that
      neuropeptide induction of MMP-9 expression occurs at the level of transcription.
      These data indicate that neuropeptides can regulate MMP activity, which, in turn,
      could facilitate prostate cancer progression.

PMID- 9766655
TI  - Role of E2F-1 in chemosensitivity.
AB  - The E2F family of transcription factors, in partnership with DP proteins, is
      thought to regulate transcription of genes that encode protein products that are
      required for DNA synthesis, which include important cancer chemotherapeutic
      targets such as thymidylate synthase and dihydrofolate reductase. This study was
      conducted to investigate the effects of overexpression of human E2F-1 cDNA on
      chemosensitivity in a human fibrosarcoma cell line, HT-1080. The E2F-1
      overexpressing HT-1080 cells had a shorter doubling time both in vitro and in
      vivo. Associated with an up-regulation of TS, E2F-1-transfected cells were more
      resistant to 5-fluorouracil than were untransfected cells. These E2F-1
      transfectants, although resistant to fluoropyrimidines and serum deprivation,
      were more sensitive to etoposide, doxorubicin, and SN38 (the active metabolite of
      irinotecan) but not to Taxol.

PMID- 9766656
TI  - Activation of JNK and p38 but not ERK MAP kinases in human skin cells by 5
      aminolevulinate-photodynamic therapy.
AB  - 5-Aminolevulinate (ALA) photodynamic therapy (PDT) is being used clinically for
      the treatment of skin cancers. ALA is applied as a precursor of porphyrins
      serving as endogenous photosensitizers. Irradiation of HaCaT cells preincubated
      with 1 mM ALA for 24 h with red light of 570-750 nm at a dose of 4.5 J/cm2 leads
      to a 6-fold elevation of cellular c-Jun N-terminal kinase activity;
      phosphorylation of p38 mitogen-activated protein kinase (MAPK) is enhanced to a
      similar extent. In contrast, neither activation nor increased phosphorylation of
      the extracellular stimulus-regulated kinase MAPKs is detected. p38 is also
      phosphorylated by ALA-PDT in the human melanoma cell lines Bro and SkMel-23,
      applying doses that lead to 80-95% cell death after 24 h. Hence, the effects of
      ALA-PDT on MAPKs are similar to stresses like UV irradiation or exposure to
      hydrogen peroxide with respect to activation of JNK and p38 MAPKs. They are
      different, however, in that extracellular stimulus-regulated kinase activity is
      not raised by ALA-PDT. Of the 830 pmol porphyrins/mg protein that were present at
      24 h in HaCaT cells, 99 pmol/mg were intracellular. When extracellular porphyrins
      had been removed by washing, p38 responses were retained. Thus, intracellular
      porphyrins synthesized from ALA are sufficient to elicit activation of p38 on
      photosensitization.

PMID- 9766657
TI  - Elevation of alpha2-->6 sialyltransferase and alpha1-->2 fucosyltransferase
      activities in human choriocarcinoma.
AB  - Structures of N-linked sugar chains are species and tissue specific and change in
      the course of tumorigenesis. Sialyl linkages of human placental glycoproteins are
      exclusively Neu5Ac alpha2-->3Gal, whereas Fuc alpha1-->2Gal and Neu5Ac alpha2-
      >6Gal residues are expressed in human chorionic gonadotropin and alkaline
      phosphatase, which are produced in human choriocarcinoma JEG-3 and BeWo cells. In
      the present study, to elucidate the enzymological and molecular biological basis
      of the structural changes that occur in the course of tumorigenesis, alpha1-->2
      fucosyltransferase, alpha2-->3 and alpha2-->6 sialyltransferase activities, and
      the expression levels of the corresponding mRNAs were measured. The alpha2-->3
      sialyltransferase activity did not change as a result of tumorigenesis; however,
      the alpha2-->6 siayltransferase activity and alpha1-->2 fucosyltransferase
      activity in JEG-3 and BeWo cells increased to levels several times higher than
      those in placenta Competitive PCR analysis showed that the expression levels of
      mRNA encoding alpha1-->2 fucosyltransferase and mRNA encoding alpha2-->6
      sialyltransferase increased significantly as a result of tumorigenesis,
      indicating that such structural changes are regulated at the level of
      transcription of these glycosyltransferase genes.

PMID- 9766658
TI  - Immunohistochemical demonstration of carcinogen-DNA adducts in tissues of rats
      given 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP): detection in
      paraffin-embedded sections and tissue distribution.
AB  - A polyclonal antibody against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
      (PhIP)-DNA adducts was raised for their immunohistochemical demonstration in
      paraffin-embedded sections. Specificity of this antibody was confirmed by
      competitive ELISA. Positive signals were immunohistochemically detected in
      acetone-fixed but not in formalin- or ethanol-fixed sections from F344 rats
      treated by gavage with a single dose of PhIP at 37.5-300 mg/kg and killed at 1,
      2, and 7 days thereafter. Dose-dependent positive staining was observed in almost
      all organs of both sexes, including the colon, prostate, and mammary gland but
      largely independent of the tumor response. Repair activity, judged by
      disappearance of adducts with time, differed according to the organ or cell type.
      One exception was hepatocytes, the liver incidentally being a nontarget organ.
      The results suggest that the generated antibody is applicable for detection of
      cells targeted by PhIP in paraffin-embedded sections and also for the
      investigation of the mechanisms of PhIP-carcinogenesis.

PMID- 9766659
TI  - Squamous cell hyperplastic foci: precursors of cutaneous papillomas induced in
      SENCAR mice by a two-stage carcinogenesis regimen.
AB  - We have conducted a series of experiments to characterize the lesions that are
      precursors of cutaneous papillomas in SENCAR mice initiated with 7,12
      dimethylbenz(a)anthracene (DMBA) and promoted with 12-O-tetradecanoylphorbol-13
      acetate (TPA). The first grossly detectable lesions at sites where papillomas
      subsequently developed were papules, slightly raised areas of skin ranging in
      diameter from 0.25 to approximately 1.5 mm. Papules were first detected in DMBA
      initiated mice 21 days after the start of dosing with TPA. Of 78 DMBA/TPA-induced
      papules tracked during 15 weeks of TPA treatments, 68% progressed to papillomas,
      9% persisted as papules, and 22% completely regressed. Histological evaluation of
      serial sections of 69 DMBA/TPA-induced papules revealed that they were focal
      hyperplastic lesions that we refer to as squamous cell hyperplastic foci (SCHF).
      These hyperproliferative lesions appeared to progress through two distinct
      stages. Stage I SCHF were characterized as regular hyperplastic foci involving
      the interfollicular epidermis and the outer root sheaths of 1 or more hair
      follicles down to the level of the sebaceous glands. Stage II SCHF were foci of
      irregular epithelial hyperplasia with increased fibrovascular stroma and involved
      from 3 to >10 hair follicles. Prominent dilated capillaries and inflammatory cell
      infiltrates were frequently associated with both stage I and II SCHF. Ha-ras gene
      codon 61 mutations were detected in 7 of 10 stage I SCHF and 13 of 14 stage II
      SCHF microdissected from histological sections and 7 of 7 of whole papules by
      mutation-specific PCR analysis. These data provide molecular evidence that SCHF
      are foci of initiated cells. Further study of these lesions may contribute to
      more fully defining the sequence of molecular and cellular changes necessary for
      tumorigenesis in mouse skin. SCHF may also have utility as early indicators of
      potential skin tumorigenicity in cancer bioassays.

PMID- 9766660
TI  - Human single-chain Fv antibodies to MUC1 core peptide selected from phage display
      libraries recognize unique epitopes and predominantly bind adenocarcinoma.
AB  - The tumor-associated antigen MUC1 is overexpressed and underglycosylated in human
      adenocarcinomas of diverse origins, such as breast, ovary, and colon. We isolated
      and describe five human single-chain (sc) Fv antibodies specific for the MUC1
      variable number of tandem repeats region isolated by in vitro selection from a
      large naive phage antibody library containing over 6 x 10(9) different scFv
      antibodies. A synthetic biotinylated 100-mer peptide corresponding to five tandem
      repeats of the MUC1 peptide core was used for selection. Two of the antibodies
      were highly specific for MUC1 as judged by ELISA and flow cytometry. In
      immunohistochemistry, antibody clone 10A stained MUC1 in the cytoplasm and
      membrane of adenocarcinoma cells of breast and ovary, whereas in normal
      epithelium, only cytoplasmic or no staining was observed. With antibody clone
      10B, staining was less pronounced and was not always membrane associated in
      adenocarcinoma. Determination of the fine specificity of 10A and 10B using a
      novel "indirect epitope fingerprinting" ELISA showed that both antibodies
      recognize unique epitopes that have not been described for hybridoma-derived anti
      mucin antibodies of mouse origin. The selected human antibodies, like many of the
      murine MUC1 antibodies, recognize epitopes on the protein core of MUC1 that are
      abundantly present in the underglycosylated form of cell surface mucin on
      adenocarcinoma. The best human scFv, clone 10A, appears to distinguish normal
      cells from adenocarcinoma cells, which makes it an attractive candidate for use
      in antibody-based tumor targeting.

PMID- 9766661
TI  - Imaging herpes virus thymidine kinase gene transfer and expression by positron
      emission tomography.
AB  - We report a series of studies that assess the feasibility and sensitivity of
      imaging of herpes virus type one thymidine kinase (HSV1-tk) gene transfer and
      expression with [124I]-5-iodo-2'-fluoro-1-beta-D-arabinofuranosyluracil ([124I]
      FIAU) and positron emission tomography (PET) and the ability of [124I]-FIAU-PET
      imaging to discriminate different levels of HSV1-tk gene expression. Studies were
      performed in rats bearing multiple s.c. tumors derived from W256 rat carcinoma
      and RG2 rat glioma cells. In the first set, we tested the sensitivity of [124I]
      FIAU-PET imaging to detect low levels of HSV1-tk gene expression after retroviral
      mediated gene transfer. HSV1-tk gene transduction of one of preestablished wild
      type W256 tumor in each animal was accomplished by direct intratumoral injection
      of retroviral vector-producer cells (W256-->W256TK* tumors). Tumors produced from
      W256 and W256TK+ cells served as the negative and positive control in each
      animal. Highly specific images of [124I]-FIAU-derived radioactivity were obtained
      in W256TK* tumors (that were transduced in vivo) and in W256TK+ tumors but not in
      nontransduced wild-type W256 tumors. The level of "specific" incorporated
      radioactivity in transduced portions of both W256TK* and W256TK+ tumors was
      relatively constant between 4 and 50 h. In the second set, we tested whether
      [124I]-FIAU and PET imaging can measure and discriminate between different levels
      of HSV1-tk gene expression. Multiple s.c. tumors were produced from wild-type RG2
      cells and stably transduced RG2TK cell lines that express different levels of
      HSV1-tk. A highly significant relationship between the level of [124I]-FIAU
      accumulation [% injected dose/g and incorporation constant (Ki)] and an
      independent measure of HSV1-tk expression (sensitivity of the transduced tumor
      cells to ganciclovir, IC50) was demonstrated, and the slope of this relationship
      was defined as a sensitivity index. We have demonstrated for the first time that
      highly specific noninvasive images of HSV1-tk expression in experimental animal
      tumors can be obtained using radiolabeled 2'-fluoro-nucleoside [124I]-FIAU and a
      clinical PET system. The ability to image the location (distribution) of gene
      expression and the level of expression over time provides new and useful
      information for monitoring clinical gene therapy protocols in the future.

PMID- 9766662
TI  - Tumor growth inhibition induced in a murine model of human Burkitt's lymphoma by
      a proteasome inhibitor.
AB  - Cell growth and viability are dependent on the function of the multicatalytic
      proteinase complex (proteasome), a multisubunit particle that affects progression
      through the mitotic cycle by degradation of cyclins. Exposure of rodent
      fibroblasts and human lymphoblasts in culture to benzyloxycarbonyl-leucyl-leucyl
      phenylalaninal (Z-LLF-CHO), a cell-permeable peptidyl aldehyde inhibitor of the
      chymotrypsin-like activity of the proteasome, resulted in the induction of
      apoptosis in a rapid, dose-dependent fashion. Fibroblasts transformed with ras
      and myc, lymphoblasts transformed by c-myc alone, and a Burkitt's lymphoma (BL)
      cell line that overexpresses c-Myc were up to 40-fold more susceptible to
      apoptosis than were either primary rodent fibroblasts or immortalized
      nontransformed human lymphoblasts, respectively. To determine whether such
      preferential apoptosis could impact upon tumor growth in vivo, toxicological
      studies were performed in mice with severe combined immunodeficiency and showed
      that mice tolerated single interscapular doses of Z-LLF-CHO without unacceptable
      toxicity. Severe combined immunodeficient mice bearing s.c. BL tumors in the
      flank were treated interscapularly with Z-LLF-CHO or a comparable dose of the
      peptidyl alcohol (Z-LLF-OH), which does not induce proteasome inhibition or
      apoptosis. Single doses of Z-LLF-CHO induced statistically significant (P <
      0.0001) early tumor regression and a significant (P < 0.0001) delay in tumor
      progression. Analysis of tumor specimens revealed increased apoptosis in BL
      tumors from mice treated with Z-LLF-CHO. These results, showing a 42% tumor
      growth delay, indicate that proteasome inhibitors have the potential of curbing
      the growth of a c-myc-related tumor.

PMID- 9766663
TI  - Functional nucleoside transporters are required for gemcitabine influx and
      manifestation of toxicity in cancer cell lines.
AB  - Gemcitabine (2',2'-difluorodeoxycytidine) is a novel pyrimidine nucleoside drug
      with clinical efficacy in several common epithelial cancers. We have proposed
      that gemcitabine requires nucleoside transporter (NT) proteins to permeate the
      plasma membrane and to exhibit pharmacological activity. In humans, there are
      seven reported distinct NT activities varying in substrate specificity, sodium
      dependence, and sensitivity to inhibition by nitrobenzylthioinosine (NBMPR) and
      dipyridamole. To determine which NTs are required for gemcitabine-dependent
      growth inhibition, cultures from a panel of 12 cell lines with defined plasma
      membrane NT activities were incubated with different concentrations of
      gemcitabine. Cell proliferation was assessed by the sulforhodamine B assay and
      cell enumeration to identify the concentrations of gemcitabine that inhibited
      cell replication by 50% (IC50s). NT activity was a prerequisite for growth
      inhibition in vitro because: (a) the nucleoside transport-deficient cells were
      highly resistant to gemcitabine; and (b) treatment of cells that exhibited only
      equilibrative NT activity with NBMPR or dipyridamole increased resistance to
      gemcitabine by 39- to 1800-fold. These data suggested that the type of NT
      activities possessed by a cell may be an important determinant of its sensitivity
      to gemcitabine and that NT deficiency may confer significant gemcitabine
      resistance. We analyzed the uptake kinetics of [3H]gemcitabine by each of five
      human NT activities in cell lines that exhibited a single NT activity in
      isolation; transient transfection of the cDNAs encoding the human concentrative
      NT proteins (hCNT1 and hCNT2) was used to study the cit and cif activities,
      respectively. The efficiency of gemcitabine uptake varied markedly among the cell
      lines with single NTs: es approximately = cit > ei > cib >>> cif. The
      transportability of [3H]gemcitabine was demonstrated by reconstitution of the
      human es NT in proteoliposomes, confirming that gemcitabine permeation is a
      protein-mediated process.

PMID- 9766664
TI  - Reduction of dimesna to mesna by the isolated perfused rat liver.
AB  - Mesna is administered with ifosfamide and cyclophosphamide to reduce the
      incidence of hemorrhagic cystitis. In the present model of mesna metabolism and
      disposition, mesna is rapidly and irreversibly oxidized to dimesna in the plasma,
      passes unchanged through the liver, and is then reduced by the kidney and
      excreted. Our detection of a high ratio of mesna to dimesna in the plasma of
      clinical samples led us to reinvestigate the hepatic metabolism of mesna and
      dimesna. We perfused isolated rat livers from female Sprague Dawley rats with
      protein-free buffered solution containing dimesna at concentrations observed
      during therapy. In single-pass perfusions, each liver was perfused with up to
      three dimesna concentrations during consecutive 20-min periods. Recirculating
      perfusions were used to study single supratherapeutic concentrations of dimesna
      or mesna. Mesna and dimesna concentrations were measured by specific
      chromatographic procedures. Dimesna reduction, adjusted by the effluent flow rate
      and liver weight (0.4-58.5 nmol/min/g liver), correlated closely by linear
      regression (r = 0.98; n = 36) to the perfused dimesna concentration (4.2-249
      microM), indicating a clearance of 0.20 ml/min/g liver. The concentration of
      dimesna that entered the liver closely matched the summed concentration of mesna
      and dimesna emerging in the effluent perfusate (single-pass experiments: slope,
      0.98; intercept, -0.30; r = 1.00; n = 31). Only trace amounts of unidentified
      thiols were detected in the bile during recirculation of perfusates with 1 mM
      mesna or 250 microM dimesna. The effluent mesna concentration correlated
      inversely with the flow rate, which was consistent with a low extraction ratio in
      the perfusion model. These data suggested that the dimesna reduction rate was
      limited by hepatic uptake. Dimesna reduction was decreased by agents that deplete
      glutathione. Pretreatment of rats with up to 100 mg/kg ifosfamide did not impair
      hepatic dimesna reduction. In control experiments, dimesna was not reduced during
      recirculation through the apparatus without a liver. Mesna was oxidized to
      dimesna during oxygenation of the perfusate in the reservoir, but mesna injected
      directly into the perfusate just before entry into the liver passed unchanged
      into the effluent. Extrapolation of the dimesna clearance data from the perfusion
      model to humans suggests that hepatic dimesna reduction may counterbalance the
      rapid oxidation of mesna in plasma. The proposed equilibrium is consistent with
      clinical observations and suggests a new model for mesna metabolism and
      disposition.

PMID- 9766665
TI  - Phase I trial of temozolomide using an extended continuous oral schedule.
AB  - Temozolomide, a methylating imidazotetrazinone, has antitumor activity against
      gliomas, malignant melanoma, and mycosis fungoides and is presently administered
      as a 5-day oral schedule every 4 weeks. This Phase I study aimed to determine the
      maximum tolerated dose of temozolomide administered as a single oral daily dose
      for a continuous 6- or 7-week period, evaluate the plasma pharmacokinetics on
      this schedule, and compare total plasma exposure over 7 weeks with the
      conventional 5-day regimen. Twenty-four patients with varying tumor types (17 of
      24 gliomas) received temozolomide. All had clinically evaluable, refractory
      disease; normal renal, hepatic, and bone marrow function; and WHO performance
      status < or = 2. Temozolomide was administered at 50 mg/m2/day, increasing by 25
      mg/m2/day/cohort until at 100 mg/m2/day grade 4 myelotoxicity forced dose
      reductions to 85 mg/m2/day, then 75 mg/m2/day. At 75 mg/m2/day the regimen was
      extended to 7 weeks, allowing the future potential combination with irradiation
      for primary gliomas. Patient responses (standard Union International Contre
      Cancer criteria; for gliomas objective response) and toxicity were assessed.
      Temozolomide plasma pharmacokinetics were determined on day 1 and at the
      beginning of the final week of administration (n = 5). The most frequent
      toxicities were myelosuppression and grades 1 and 2 nausea and vomiting. Grade 4
      leucopenia and thrombocytopenia occurred in one of four patients receiving 100
      mg/m2/day temozolomide and in one of seven patients receiving 85 mg/m2/day. These
      hematological toxicities did not exceed grade 2 in 10 patients receiving 75
      mg/m2/day temozolomide. One of 4 malignant melanoma patients and 7 of 17 glioma
      patients (41%) demonstrated tumor responses. The overall response rate for this
      prolonged schedule was 33% (objective response, 7 of 24 patients; partial
      response, 1 of 24 patients); also, 6 of 17 glioma patients maintained SD. Peak
      plasma temozolomide concentrations were obtained 30-90 min after oral
      administration. Elimination in plasma was best described by a monoexponential
      equation with an elimination half-life of 96 +/- 16 min. No plasma accumulation
      of temozolomide occurred. Toxicity was greatest in higher dose cohorts, with a
      resultant maximum tolerated dose of 85 mg/m2/day, whereas lower dose cohorts
      tolerated the schedule well. The area under the temozolomide plasma versus time
      curve was noncumulative between the first and last week of the schedule.
      Temozolomide administration of 75 mg/m2/day over a 7-week period permits a 2.1
      fold greater drug exposure/4 weeks in comparison with the 5-day schedule of 200
      mg/m2/day repeated every 28 days. The overall response rate was 33% (glioma
      patients, 41% and a further 25% SD). Temozolomide (75 mg/m2/day) for 7 weeks is
      the recommended starting dose for further assessment of this schedule.

PMID- 9766666
TI  - Reversal of CPT-11 resistance of lung cancer cells by adenovirus-mediated gene
      transfer of the human carboxylesterase cDNA.
AB  - To evaluate the concept that transfer of the human carboxylesterase (CE) gene
      will overcome the drug resistance of a solid tumor to CPT-11 (irinotecan), we
      used an adenovirus vector (AdCMV.CE) carrying human CE cDNA to infect CPT-11
      resistant A549 human adenocarcinoma cells (A549/CPT) in vitro and in vivo and
      evaluated cell growth over time. The A549/CPT cells, selected by stepwise and
      continuous exposure of parental A549 cells to CPT-11 over 10 months, had a 6-fold
      resistance to CPT-11 and 42% CE activity in comparison with parental A549 cells.
      AdCMV.CE infection resulted in an increase in functional CE protein in resistant
      cells in vitro that was sufficient to convert CPT-11 to its active metabolite, SN
      38, and effectively suppressed resistant cell growth in vitro in the presence of
      CPT-11. When AdCMV.CE was directly injected into established s.c. resistant A549
      based tumors in nude mice receiving CPT-11, there was a 1.8-fold reduction in
      tumor size at day 20 compared to that of controls (P < 0.05). These observations
      suggest that adenovirus-mediated gene transfer of the human CE gene and
      concomitant administration of CPT-11 may have potential as a strategy for local
      control of acquired CPT-11 resistance of solid tumors.

PMID- 9766668
TI  - Influence of melatonin on invasive and metastatic properties of MCF-7 human
      breast cancer cells.
AB  - Melatonin, the principal pineal gland hormone, exerts a direct antiproliferative
      effect on estrogen-responsive MCF-7 cells in culture. The purpose of the current
      study was to investigate the effects of melatonin on the invasion capacity of MCF
      7 cells. In vitro, melatonin at physiological doses (1 nM) reduced (P < 0.001)
      the invasiveness of tumoral cells measured in Falcon invasion chambers.
      Subphysiological (0.1 pM) and pharmacological concentrations (10 microM) of
      melatonin failed to inhibit cell invasion. Melatonin was also able to block
      17beta-estradiol-induced invasion (P < 0.001). Pretreatment of MCF-7 cells with 1
      nM melatonin increased the response of tumoral cells to the anti-invasive effects
      of this indolamine. To explore possible mechanisms by which melatonin reduces
      invasiveness, we measured the attachment of MCF-7 cells to a basement membrane,
      the chemotactic response of the cells, and their type IV collagenolytic activity.
      The presence of melatonin (1 nM) in the culture medium significantly reduced the
      ability of MCF-7 cells to attach to the basement membrane; this effect was
      enhanced by pretreating the cells with the same indolamine (P < 0.001). Melatonin
      also counteracts the stimulatory effects of 17beta-estradiol on cell adhesion (P
      < 0.001). The chemotactic response of MCF-7 cells also decreased in the presence
      of 1 nM melatonin, and this melatonin-induced reduction of cell migration was
      more effective on cells that were previously incubated for 5 days with melatonin
      than it was on nonpretreated cells (P < 0.001). The simultaneous addition of
      17beta-estradiol and melatonin resulted in a significantly lower chemotactic
      response than that of 17beta-estradiol-treated cells (P < 0.001). However, type
      IV collagenolytic activity was not influenced by melatonin. Our results
      demonstrate that melatonin reduces the invasiveness of MCF-7 cells, causing a
      decrease in cell attachment and cell motility, probably by interacting with the
      estrogen-mediated mechanisms of MCF-7 cell invasiveness. In addition, we also
      studied the influence of melatonin on the expression of two cell surface adhesion
      molecules (E-cadherin and beta1 integrin) and an intermediate filament protein
      (vimentin), the expression of which has been correlated with the relative
      invasive capacity of human breast cancer cells. The culture of tumor cells in the
      presence of melatonin (1 nM) increased the membrane staining for E-cadherin and
      beta1 integrin as well as the number of E-cadherin and beta1 integrin
      immunoreactive cells (P < 0.01). Neither control MCF-7 cells nor those treated
      with melatonin stained for vimentin. Preliminary in vivo experiments carried out
      on ovariectomized athymic nude mice implanted with 17beta-estradiol pellets and
      inoculated with 5 x 10(6) MCF-7 cells in the inguinal mammary fat pad suggest
      that melatonin could decrease the tumorigenicity of these tumor cells. However,
      these results need further confirmation. Taken together, our results suggest that
      melatonin shifts MCF-7 human breast cancer cells to a lower invasive status by
      increasing the beta1 integrin subunit and E-cadherin expression and promoting the
      differentiation of tumor cells. Finally, our study points out the existence of
      the anti-invasive actions of melatonin as a part of the oncostatic action of
      melatonin.

PMID- 9766667
TI  - Inhibition of phosphoinositide 3-kinase related kinases by the radiosensitizing
      agent wortmannin.
AB  - Members of the phosphatidylinositol-3 kinase related kinase (PIKK) family
      function in both cell cycle progression and DNA damage-induced cell cycle
      checkpoints. The fungal metabolite, wortmannin, is an effective radiosensitizer
      that irreversibly inhibits certain members of the PIKK family. Based on their
      roles in DNA damage responses, several PIKKs, DNA-dependent protein kinase (DNA
      PK), ataxia telangiectasia mutated (ATM) and the ataxia- and Rad3-related protein
      (ATR), are potential targets for the radiosensitizing effect of wortmannin. In
      this report, we demonstrate that wortmannin is a relatively potent inhibitor of
      DNA-PK (IC50, 16 nM) and ATM (IC50, 150 nM) activities, whereas ATR activity is
      significantly less sensitive to this drug (IC50, 1.8 microM). In intact A549 lung
      adenocarcinoma cells, wortmannin inhibited both DNA-PK and ATM at concentrations
      that correlated closely with those required for radiosensitization. Furthermore,
      pretreatment of A549 cells with wortmannin resulted in radioresistant DNA
      synthesis, a characteristic abnormality of ATM-deficient cells. These results
      identify wortmannin as an inhibitor of ATM activity and suggest that ATM and DNA
      PK are relevant targets for the radiosensitizing effect of this drug in cancer
      cells.

PMID- 9766669
TI  - Retroviral transfer of human cytochrome P450 genes for oxazaphosphorine-based
      cancer gene therapy.
AB  - Cyclophosphamide (CPA) and ifosfamide (IFA) are widely used anticancer prodrugs
      that are bioactivated in the liver by specific cytochrome P450 enzymes (CYPs).
      The therapeutic activity of these antitumor agents can be compromised by a low
      therapeutic index that is, in part, due to the systemic distribution of activated
      drug metabolites. Here, recombinant retroviruses were used to deliver six
      different CPA- or IFA-metabolizing human CYP genes to 9L gliosarcoma cells: 2B6,
      2C8, 2C9, 2C18 (Met385 and Thr385 alleles), 2C19, and 3A4. Intratumoral
      cytochrome P450 expression conferred substantial sensitivity to CPA cytotoxicity,
      with the most dramatic effects seen with CYP2B6. Strong CPA chemosensitivity was
      also seen following transduction of CYP2C18-Met, despite a very low level of CYP
      protein expression (>60-fold lower than that of 2B6). In contrast to CPA, the
      cytotoxicity of IFA was greatest toward tumor cells transduced with CYP3A4,
      followed by CYPs 2B6 and 2C18-Met. A substantial further increase in
      chemosensitivity was achieved upon transduction of 2B6 or 2C18-Met-expressing
      tumor cells with P450 reductase, which provided for more efficient intratumoral
      prodrug activation and cytotoxicity at lower drug concentrations. With 2B6- plus
      P450 reductase-transduced tumor cells, CPA but not IFA conferred a strong cell
      contact-independent bystander cytotoxic effect on non-P450-expressing 9L cells.
      CPA treatment of tumors that were transduced with 2B6 or 2C18-Met together with
      P450 reductase and were grown s.c. in immunodeficient mice resulted in a large
      enhancement of the liver P450-dependent antitumor effect seen with control 9L
      tumors, with no apparent increase in host toxicity (growth delay of >25-50 days
      in P450-expressing tumors versus approximately 5-6 days without P450). CYP2B6
      plus P450 reductase and CYP2C18-Met plus P450 reductase thus appear to be
      excellent gene combinations for use with CPA in P450/prodrug activation-based
      cancer gene therapy.

PMID- 9766670
TI  - p53 mutations in skin and internal tumors of xeroderma pigmentosum patients
      belonging to the complementation group C.
AB  - Fifty-eight skin biopsies and three primary internal tumors from patients
      affected by the rare hereditary disease xeroderma pigmentosum (XP) were studied
      by an improved PCR-single strand conformation polymorphism analysis to detect the
      mutations of the tumor suppressor gene p53. The results from cutaneous XP tumors,
      including 27 squamous cell carcinomas and 6 basal cell carcinomas, show a very
      high level (86%) of p53 mutations. The analysis of mutations found in XP skin
      cancers according to the complementation group of the patients shows that tandem
      CC-->TT transitions are a characteristic of XP-C patients with a frequency much
      higher in their skin tumors (85%) compared with tumors in XP patients who do not
      belong to group C (33%). In all XP-C biopsies, mutations were due to replication
      of unrepaired DNA lesions on the nontranscribed strand of the p53 gene,
      substantiating the preferential repair in vivo of the transcribed strand of this
      gene in human tissues. For the first time, we were able to analyze three primary
      internal tumors (a neuroendocrine tumor of the thyroid, a gastric adenocarcinoma,
      and a glioma of the brain) of young XP children. All of them contained one
      mutation on the p53 gene, which were different from the ones found in the XP skin
      tumors and could have resulted from unrepaired lesions caused by oxidative
      damage.

PMID- 9766671
TI  - Apurinic endonuclease (Ref-1) is induced in mammalian cells by oxidative stress
      and involved in clastogenic adaptation.
AB  - Apurinic endonuclease (APE; also known as Ref-1 protein) is a key enzyme in base
      excision repair, cleaving apurinic sites that arise spontaneously because of the
      activity of DNA glycosylases. To address the question of whether APE can be
      modulated by genotoxic stress affecting cellular protection, we analyzed the
      expression of APE in Chinese hamster ovary (CHO) cells after treatment with
      various genotoxic agents. We show that treatment of CHO cells with hydrogen
      peroxide (H2O2) or sodium hypochlorite (NaOCl) increases the levels of APE mRNA
      and protein. APE induction was observed 3-9 h after treatment and was accompanied
      by an increase in APE activity. We also show that the cloned human APE promoter
      transfected into CHO cells is stimulated by the oxidants, indicating
      transcriptional activation of the APE gene. When cells were pretreated with
      NaOCl, inducing APE, and then challenged with H2O2, the clastogenic effect of the
      challenge dose was significantly reduced, suggesting clastogenic adaptation due
      to APE induction. To further prove the involvement of APE in adaptation against
      induced chromosomal breakage, we transfected human APE cDNA driven by an
      inducible promoter into CHO cells and observed that transient induction of APE
      reduced the clastogenic effect of H2O2. Overall, the data demonstrate that the
      APE gene can be activated by oxidative agents, resulting in a transient increase
      in APE repair activity, which reduces the clastogenic response of cells to an
      oxidative agent. The protection of cells from chromosomal aberrations seen after
      prior exposure to oxidants is attributed to an adaptive response to oxidative
      stress.

PMID- 9766672
TI  - Mutation of the MENIN gene in sporadic pancreatic endocrine tumors.
AB  - Pancreatic endocrine tumors occur both sporadically and as part of the multiple
      endocrine neoplasia type 1 (MEN1) syndrome. MEN1 is an autosomal dominant disease
      characterized by parathyroid hyperplasia, pancreatic endocrine tumors, and
      pituitary adenomas. The MEN1 gene called MENIN maps to chromosome 11q13 and is
      thought to function as a tumor suppressor gene. We previously demonstrated loss
      of heterozygosity (LOH) at 11q13 in approximately 40% of sporadic pancreatic
      endocrine tumors and hypothesize that MENIN is involved in the development of
      these tumors. Thirty-one sporadic pancreatic endocrine tumors were analyzed for
      mutation of MENIN by nonradioactive single-stranded conformation polymorphism.
      Twelve mutations were detected in 31 sporadic pancreatic endocrine tumors (34%).
      Twelve of these 31 tumors previously demonstrated loss of heterozygosity at
      11q13. Of the tumors with LOH, seven contained mutations of the MENIN gene (58%).
      The majority of the MENIN mutations occurred within exon 2. Two independent
      mutations in MENIN were detected in a gastrinoma that also revealed LOH, leading
      to the possibility of another tumor suppressor gene locus at 11q13. Mutations
      were present in both benign and malignant pancreatic endocrine tumors, suggesting
      that a MENIN gene mutation is a frequent and early event in the tumorigenesis.
      The high incidence of truncating mutations in tumors with LOH at 11q13 support
      the hypothesis that MENIN is a tumor suppressor gene.

PMID- 9766673
TI  - High incidence of loss of heterozygosity in breast tumors from carriers of the
      BRCA2 999del5 mutation.
AB  - Germ-line mutation in the BRCA2 gene confers an increased risk of breast cancer.
      An elevation of additional genetic defects in tumors of patients with germ-line
      mutation in the BRCA2 gene compared with sporadic breast tumors has been
      reported. To evaluate the nature of the difference, we did detailed mapping of
      chromosomes 1p, 3p, 6q, 11, 13q, 16q, 17, and 20q, using microsatellite markers.
      We found that the frequency of loss of heterozygosity was similar at some
      chromosomal regions in the BRCA2 999del5 and sporadic tumors but significantly
      different at others. These others include chromosomal arms 3p, 6q, 11p, 11q, 13q,
      and 17p. Loss of heterozygosity mapping suggests that the same chromosome regions
      are involved in both tumor groups but at elevated frequencies in BRCA2 999del5
      tumors. This higher frequency of genetic aberrations could pinpoint genes that
      selectively promote tumor progression in individuals predisposed to breast cancer
      due to the BRCA2 999del5 germ-line mutation. Accumulation of somatic genetic
      changes during tumor progression may follow a specific and more aggressive
      pathway of chromosome damage in these individuals.

PMID- 9766674
TI  - Insulin-like growth factor II and PAX3-FKHR cooperate in the oncogenesis of
      rhabdomyosarcoma.
AB  - The mouse myoblast C2C12 cell line transfected singly with cDNA for Pax-3, PAX3
      FKHR, or insulin-like growth factor (IGF) II or cotransfected with IGF-II plus
      Pax-3 or with IGF-II plus PAX3-FKHR genes showed an altered morphology, a lack of
      differentiation, and higher proliferation rates in vitro. On s.c. injection into
      nude mice, tumors grew from transfected cell lines but not from cells transfected
      with the empty vector. Tumors derived from IGF-II/PAX3-FKHR- and IGF-II
      transfected cells grew most rapidly. Cotransfection of IGF-II plus Pax-3 induced
      tumors comprised highly differentiated striated muscle cells; Pax-3, PAX3-FKHR,
      or IGF-II transfection produced tumors at varying stages of differentiation.
      Tumors derived from IGF-II plus PAX3-FKHR-cotransfected cells were composed of
      undifferentiated cells. This was the only tumor type to infiltrate the underlying
      muscle. The most angiogenesis and the least apoptosis were observed in the latter
      tumors. These results support the hypothesis that PAX3-FKHR interacts with IGF-II
      to play a critical role in the oncogenesis of rhabdomyosarcoma.

PMID- 9766675
TI  - Aberrant expression of double-stranded RNA-dependent protein kinase in
      hepatocytes of chronic hepatitis and differentiated hepatocellular carcinoma.
AB  - We immunohistochemically analyzed the expression of double-stranded RNA-dependent
      protein kinase (PKR) using a monoclonal antibody, 71/10. Test samples included 64
      human liver biopsies and 25 liver sections of rats inoculated with
      diethylnitrosamine. The PKR signals in human fatty livers and normal rat livers
      were minimum. Scoring signal intensity from 0-4, the average scores of chronic
      active (14 cases) and chronic persistent (6 cases) hepatitis associated with
      hepatitis virus C (HCV) were 2.8 and 2.0, respectively (P = 0.038). The stained
      cells were significantly more abundant in the periportal than centrilobular
      regions for both chronic active and persistent hepatitis (P < 0.001 each). The
      average score of liver cirrhosis associated with HCV was 1.9. Those scores of
      well-, moderately, and poorly differentiated hepatocellular carcinomas associated
      with HCV were 3.4, 2.1, and 0.3, respectively (P < 0.001 for each pair). Those
      scores of well- and poorly differentiated carcinomas associated with hepatitis
      virus B were 2.3 and 0.0, respectively (P < 0.001). The average score of rat
      carcinomas induced by diethylnitrosamine was 1.9. Morphologically, nuclei of the
      vast majority of PKR-positive cells looked not apoptotic. The ratio of PKR
      positive cells to apoptotic cells by terminal transferase-mediated dUTP nick end
      labeling method was approximately 20 in hepatitis, and over 100 in well
      differentiated carcinoma.

PMID- 9766676
TI  - Inhibition of tumor cell growth by RTP/rit42 and its responsiveness to p53 and
      DNA damage.
AB  - Through a differential screening technique, we have identified a cDNA clone with
      differential expression in normal versus tumor cells. This clone, designated
      rit42 (reduced in tumor, 42 kDa), was previously isolated as a homocysteine
      inducible gene in human endothelial cells (RTP), and the same or a highly related
      androgen-responsive gene in mouse has also been identified. Both Northern blot
      analysis and in situ hybridization demonstrated a significantly diminished
      expression in tumor cells, including those derived from breast and prostate when
      compared with normal cells. It was shown that RTP/rit42 mRNA cycles with cell
      division, peaking at G1 and G2-M, with lower expression in S phase. The biphasic
      expression of RTP/rit42 mRNA was absent in tumor cells. Introduction of rit42
      cDNA into human cancer cells reduced cell growth both in vitro and in nude mice.
      Moreover, analysis of a tetracycline-regulated p53-inducible system in null-p53
      cell lines showed that RTP/rit42 mRNA expression increased concomitantly with p53
      expression and followed a similar time course. In addition, DNA-damaging agents
      induced RTP/rit42 expression in a p53-dependent manner but independent of a p53
      mediated G1 arrest. Immunofluorescence analysis of a FLAG epitope-tagged
      RTP/rit42 protein revealed a cytoplasmic localization pattern with redistribution
      to the nucleus upon DNA damage. We have localized RTP/rit42 to human chromosome
      8q24.3. Taken together, these results are consistent with a growth inhibitory
      role for RTP/rit42, and its down-regulation may contribute to the tumor malignant
      phenotype.

PMID- 9766677
TI  - Multiple changes in gene expression are associated with normal cell-induced
      modulation of the neoplastic phenotype.
AB  - Specific regulatory pathways in neoplastic cells seem to be responsive to control
      signals provided by the normal cell/tissue environment. The present experiments
      were designed to define, at the molecular level, the growth-regulatory signals in
      neoplastic cells that are associated with the modulation of expression of the
      neoplastic phenotype by normal cell populations. When cultured in the presence of
      normal cell-conditioned medium, a highly malignant rat tracheal carcinoma-derived
      cell population (IC-12) undergoes dramatic changes in morphology, and the
      anchorage-independent growth of these cells is inhibited. This phenomenon is
      termed normalization. The strategy adopted for elucidating the cellular/molecular
      changes associated with the induction of these phenotypic alterations was to
      define the differences in mRNA expression patterns between IC-12 populations
      exhibiting the neoplastic phenotype (wild-type cells) and those exhibiting the
      normalized phenotype. For this purpose, the differential display technique and
      subsequent Northern blot analyses were used. Once specific, differentially
      expressed genes were identified, the temporal sequence of altered gene expression
      was determined by monitoring the levels of mRNA expression after the addition of
      normal cell-conditioned medium. Some of the identified known genes are grouped
      into three general categories: (a) group I genes are those involved in cellular
      adhesion processes; (b) group II genes are those involved in signal transduction
      pathways; and (c) group III genes are those involved in transcriptional and
      translational processes. Genes that are differentially expressed during the
      normalization process seemed to exhibit characteristic temporal expression
      patterns after the addition of normal cell-conditioned medium. Identification of
      these differentially expressed genes and their associated cellular functions
      provide insight into some of those regulatory pathways in neoplastic cells that
      are amenable to regulation by normal cells. An analysis of the temporal sequence
      of altered gene expression provides further information that allows the
      identification of those genes that are likely to be critical upstream effectors
      regulating transcriptional regulatory events that result in the moderation of
      neoplastic behavior.

PMID- 9766678
TI  - Molecular ordering of apoptosis induced by anticancer drugs in neuroblastoma
      cells.
AB  - Apoptosis mediated by anticancer drugs may involve activation of death-inducing
      ligand/receptor systems such as CD95 (APO-1/Fas), cleavage of caspases, and
      perturbance of mitochondrial functions. We investigated the sequence of these
      events in SHEP neuroblastoma cells transfected with Bcl-2 or Bcl-X(L) using two
      different drugs, namely, doxorubicin (Doxo), which activates the CD95/CD95 ligand
      (CD95-L) system, and betulinic acid (Bet A), which does not enhance the
      expression of CD95 or CD95-L and which, as shown here, directly targets
      mitochondria. Apoptosis induced by both drugs was inhibited by Bcl-2 or Bcl-X(L)
      overexpression or by bongkrekic acid, an agent that stabilizes mitochondrial
      membrane barrier function, suggesting a critical role for mitochondria. After
      Doxo treatment, enhanced CD95/CD95-L expression and caspase-8 activation were not
      blocked by Bcl-2 or Bcl-X(L) and were found in cells with a mitochondrial
      transmembrane potential (delta psi(m)) that was still normal (delta psi(m)high
      cells). In marked contrast, after Bet A treatment, caspase-8 activation occurred
      in a Bcl-2- or Bcl-X(L)-inhibitable fashion and was confined to cells that had
      lost their delta psi(m) (delta psi(m)low cells). Mitochondria from cells treated
      with either Doxo or Bet A induced cleavage of both caspase-8 and caspase-3 in
      cytosolic extracts. Thus, caspase-8 activation may occur upstream or downstream
      of mitochondria, depending on the apoptosis-initiating stimulus. In contrast to
      caspase-8, cleavage of caspase-3 or poly(ADP-ribose)polymerase was always
      restricted to delta psi(m)low cells, downstream of the Bcl-2- or Bcl-X(L)
      controlled checkpoint of apoptosis. Cytochrome c, released from mitochondria
      undergoing permeability transition, activated caspase-3 but not caspase-8 in a
      cell-free system. However, both caspases were activated by apoptosis-inducing
      factor, indicating that the mechanism of caspase-8 activation differed from that
      of caspase-3 activation. Taken together, our findings demonstrate that
      perturbance of mitochondrial function constitutes a central coordinating event in
      drug-induced cell death.

PMID- 9766679
TI  - Enhanced expression of urokinase receptor induced through the tissue factor
      factor VIIa pathway in human pancreatic cancer.
AB  - Overexpression of tissue factor (TF) is characteristically observed in advanced
      pancreatic cancer and has been associated with invasion and metastasis.
      Functional responses of TF activation are here investigated using as a model
      system the human pancreatic cancer cell lines SW979 (which overexpresses TF) and
      MIAPaCa2 (which does not express detectable levels). After stimulation of these
      cell lines with factor VIIa (FVIIa), the only known TF ligand, expression of
      urokinase receptor (uPAR) gene was up-regulated in SW979 cells in a dose
      dependent manner but not in MIAPaCa2 cells. Interestingly, urokinase (uPA) and
      its specific inhibitor PAI-1 were not up-regulated. Exposure to functionally
      inactivated FVIIa did not show any effect on uPAR expression on SW979 cells
      despite binding to TF with higher efficiency. The neutralizing anti-TF antibody
      5G9 blocked the FVIIa-induced up-regulation of uPAR completely, whereas hirudin
      failed to block this up-regulation. Treatment of SW979 cells with Factor Xa did
      not up-regulate the expression of uPAR gene, whereas treatment with FVII induced
      the same level of enhanced uPAR gene expression as that with FVIIa. In the
      matrigel invasion assay, enhanced invasion of SW979 cell line induced by FVIIa
      was completely inhibited by anti-TF antibody and alpha2-antiplasmin. Moreover,
      the endogenous levels of uPAR gene expression were significantly correlated with
      the level of TF gene expression in 19 human cancer cell lines (P < 0.05). These
      data suggest that up-regulation of uPAR expression by tumor cells leading to
      tumor invasion is induced through the TF-FVIIa pathway rather than TF-initiated
      thrombin generation. This is the first report that TF may be one of the key
      receptors that can up-regulate expression of the plasminogen activator receptor
      in human cancer cells to enhance tumor invasion and metastasis.

PMID- 9766680
TI  - Selective localization of matrix metalloproteinase 9, beta1 integrins, and human
      lymphocyte antigen class I molecules on membrane vesicles shed by 8701-BC breast
      carcinoma cells.
AB  - The shedding of membrane vesicles from the cell surface is a vital process
      considered to be involved in cell-cell and cell-matrix interactions and in tumor
      progression. By immunoelectron microscopic analysis of surface replicas of 8701
      BC human breast carcinoma cells, we observed that membrane vesicles shed from
      plasma membranes contained densely clustered gelatinase B [matrix
      metalloproteinase 9 (MMP-9)], beta1 integrins, and human lymphocyte antigen class
      I molecules. By contrast, alpha-folate receptor was uniformly distributed on the
      smooth cell membrane and shedding areas. Both cell surface clustering of selected
      molecules and membrane vesicle release were evident only when cells were cultured
      in the presence of serum. Vesicle shedding occurred preferentially at the edge or
      along narrow protrusions of the cell. Specific accumulation of proMMP-9 and
      active forms of MMP-9 in shed vesicles was also demonstrated by gelatin
      zymography. In addition, Western blotting analysis showed the presence of a large
      amount of proMMP-9/tissue inhibitor of metalloproteinase 1 complex. The release
      of selected areas of plasma membranes enriched with MMP-9 and beta1 integrins
      indicates that membrane vesicle shedding from tumor cells plays an important role
      in the directional proteolysis of the extracellular matrix during cellular
      migration. The presence of human lymphocyte antigen class I antigens suggests a
      mechanism for tumor cells to escape from immune surveillance.

PMID- 9766681
TI  - Novel human malignancy-associated gene (MAG) expressed in various tumors and in
      some tumor preexisting conditions.
AB  - We have identified a novel human malignancy-associated gene (MAG) expressed in
      various malignant tumors including glioblastomas and hepatocellular carcinomas
      (HCCs) and in tumor preexisting conditions such as hepatitis C virus- and
      hepatitis B virus-induced liver cirrhosis. The expression of MAG was
      characterized using reverse transcription-PCR (RT-PCR), rapid amplification of
      cDNA ends PCR, RNA dot blotting, RNase protection assay, and Northern blot
      analysis. Rapid amplification of cDNA ends PCR yielded a 536-bp MAG fragment in
      HCC, macroregenerative liver nodules with dysplasia, and liver cirrhosis but not
      in normal liver or placenta. By RT-PCR, MAG expression was not found in 12
      different normal tissues but found in 46 of 51 (90%) premalignant and malignant
      tissues of various sites. Embryonic liver and brain were positive for MAG
      expression together with tumors from the same organs, but the corresponding
      normal adult tissues were negative. By RNase protection assay, MAG mRNA was
      expressed in the HepG2 liver tumor cell line and in an ovarian carcinoma but not
      in normal liver. The estimated transcript size from Northern blot analysis was
      8.8 kb. This novel gene may play a role in the progression of premalignant
      conditions and in the development of HCC and other cancers.

PMID- 9766682
TI  - Correspondence re: J. Benitez et al., A region of allelic imbalance in 1q31-32 in
      primary breast cancer coincides with a recombination hot spot. Cancer Res., 57:
      4217-4220, 1997.

PMID- 9766684
TI  - Electroencephalographic findings in functional psychoses: state or trait
      indicators?
AB  - The clinical significance of electroencephalographic (EEG) changes in patients
      with functional psychoses is not yet clearly defined, particularly whether these
      changes are state indicators or trait indicators. In the present review, the EEG
      abnormalities in schizophrenia are discussed. In early EEG studies of
      schizophrenics, the various specific EEG patterns were suggested to be trait
      indicators, but those findings were not confirmed. The EEG patterns of some
      patients with catatonic schizophrenia, especially periodic catatonia, were
      thought to be episode or state indicators, and some of the patients diagnosed as
      having atypical psychoses in Japan were suggested to show state indicator EEG
      findings. As the computerized and spectral analyses of EEG have advanced, the
      contradictory findings of EEG in schizophrenia have been reported, interpreted as
      'hyperstable' or 'hypernormal' EEG findings and 'hypofrontal' EEG findings (slow
      waves in the frontal region). However, no conclusion can be made as to whether
      these EEG findings are state or trait indicators. On the borderland of functional
      psychoses, the behavioral changes in temporal lobe epilepsy were described as a
      trait indicator, and the psychotic states in non-convulsive generalized status
      epilepticus and acute confusional states were suggested to be state indicators.
      Further studies of EEG abnormalities in schizophrenia are necessary from multi
      dimensional perspectives, including in comparison with the symptomatic psychoses.

PMID- 9766683
TI  - Recent advances in dementia research in Japan: non-Alzheimer-type degenerative
      dementias.
AB  - In this article, we review recent reports by Japanese researchers on non
      Alzheimer-type degenerative dementias. These dementias can be classified into the
      following subtypes: dementias with Lewy bodies, including diffuse Lewy body
      disease, dementias with neurofibrillary tangles, dementias with glial tangles,
      including progressive supranuclear palsy and corticobasal degeneration,
      argyrophilic grain dementia, frontotemporal dementias including Pick's disease;
      dementias with degeneration of subcortical nuclei, including Huntington's disease
      and, last, unclassified dementias. Recently, these various forms of dementia have
      received much attention in Japan, as elsewhere.

PMID- 9766685
TI  - Behavioral characteristics of 187 young adults with autism.
AB  - A survey was conducted on the present behavioral characteristics of 187 cases of
      adult autism in patients over 18 years of age employing Achenbach's Child
      Behavior Checklist (CBCL). When their behavioral characteristics were evaluated
      in relation to Present Language Developmental Level (PLDL) and Present Adaptive
      Level (PAL), it was seen that greater variation in behavior characteristics was
      seen among those exhibiting increasingly lower PLDL and PAL scores. Behavior
      characteristics reminiscent of depression were noted even among those exhibiting
      high PLDL. Behavior pointing to obsession was found in common among almost all
      cases of autism irrespective of PLDL or PAL. Psychotic symptoms such as
      hallucinations and delusions were absent in most cases. The results of the
      present study were indicative not only of the significance of obsessive behavior
      in autism, but also its significance in terms of delving further into the
      psychopathology of the disorder.

PMID- 9766687
TI  - The prevalence and pattern of insomnia in Japanese industrial workers:
      relationship between psychosocial stress and type of insomnia.
AB  - We examined the prevalence of insomnia among Japanese male industrial workers and
      analyzed the effect of psychosocial stress on the prevalence of three types of
      insomnia: 'difficulty in falling asleep', 'frequent sleep interruption' and
      'early morning arousal'. The study population consisted of male day workers (n =
      319) in a manufacturing heavy industry company located in Nagasaki City, Japan.
      The subjects answered a questionnaire consisting of six sleep-related items and
      24 questions related to occupational and private life conditions. A total of 271
      men (average age 40.9 years) completed the questionnaire; a response rate of 85%.
      Insomnia within the month preceding the survey was present in 27.7% of the
      workers (75/271). Multiple logistic regression analysis demonstrated that
      different psychosocial stressors were associated with different types of
      insomnia. Visual display terminal (VDT) work overload was significantly
      associated with all types of insomnia, while 'over-involvement in the job' was
      associated with difficulty in falling asleep and early morning arousal. Our
      results demonstrated that the prevalence of insomnia in Japanese workers is
      similar to that reported among European and American general adult population.
      Our results also indicate that the use of VDT in the workfield is associated with
      insomnia.

PMID- 9766686
TI  - One-year prognosis of depressive illness in the elderly population in Japan.
AB  - A 1-year prospective study of 43 elderly depressed residents (13 men and 30
      women) in Nagai City in Japan is described. An initial survey was carried out in
      1993 to find depressed residents. The subjects of the survey were 2056 residents
      of 65 years of age and older. The Japanese version of the Geriatric Depression
      Scale (GDS) was employed as a screening tool in the first phase of the survey. In
      the second phase, screened subjects and control subjects were interviewed by
      psychiatrists using the Structured Interview for DSM-III-R (SCID). The diagnosis
      of depression was made by the psychiatrists on the basis of the results of the
      SCID. Forty-three persons were judged to be depressed. At follow-up, 10 were
      still depressed and 15 were well. Four were demented. Fourteen dropped out due to
      death, hospitalization, absence from home or refusal. The results showed that
      approximately half of the elderly depressed persons seemed to recover by the time
      of the 1-year follow-up. One-year prognosis of dysthymia was the worst. Some
      types of depression seemed to be a precursor for dementia. The concern is with
      how the findings may be used as an aid in understanding and planning community
      mental health services strategies. The results indicate that it is very important
      to pay close attention to patients with depressive illness who do not meet the
      criteria for major depression.

PMID- 9766688
TI  - Personality differences in the Munich Personality Test between patients with
      major depression and panic disorder.
AB  - This study attempted to determine whether patients with major depression and
      panic disorder could be differentiated by personality features, measured by the
      Munich Personality Test (MPT). One of the six MPT personality dimensions,
      'rigidity', was developed in relation to the 'melancholic type of personality',
      which may be a specific personality feature of depressive subjects. We therefore
      hypothesized that the MPT might be sensitive to possible personality differences
      between patients with major depression and panic disorder. Sixty-six patients
      with major depression and 27 patients with panic disorder, taken from consecutive
      intakes at an outpatient unit, were compared in terms of six personality
      dimensions of the MPT. The results demonstrated that rigidity could significantly
      differentiate the two patient groups, even after the possible confounding effects
      on the personality assessments were statistically partialled out. The MPT was
      suggested to be powerful for describing distinctive personality features of
      depressive subjects from anxiety subjects.

PMID- 9766689
TI  - Tourette syndrome in Japan: a nationwide questionnaire survey of psychiatrists
      and pediatricians.
AB  - In order to shed light on the clinical picture of patients with Tourette syndrome
      (TS) treated at medical institutions in Japan, a nationwide survey covering both
      pediatric patients and psychiatric patients was conducted. We mailed 316
      questionnaires on experience in treating TS cases and the patients' present
      conditions etc. to specialists such as psychiatrists and pediatricians. A total
      of 164 responded. The survey found 154 TS patients being treated at the time of
      survey, 45 (29.2%) had obsessive-compulsive symptoms (OCS), and 10 (6.5%) had
      family histories of TS. It was suggested that TS is often associated with OCS and
      that familial cases of TS are slightly less common in Japan than they are in the
      USA. Of the 116 respondents who described their experiences, 85 (73.2%) said that
      they had treated one or more patients displaying the symptoms of frequent
      coprolalia, and 42 (36.2%) said that they had treated one or more patients
      suffering from developmental disorders. Based on these findings, we speculated
      that the rate of coprolalia in Japan is a little higher than the previously
      reported 4% and that TS is often associated with developmental disorders.

PMID- 9766690
TI  - Mental health of visually and hearing impaired students from the viewpoint of the
      University Personality Inventory.
AB  - Tsukuba College of Technology is the first national university established as an
      institute of higher education for the visually and hearing impaired. We have been
      systematically conducting a University Personality Inventory (UPI) survey on our
      students since 1989 to understand their mental health. In this study, we compared
      the UPI scores of the new students of Tsukuba College of Technology in 1993 and
      1994 with unimpaired students from the University of Tsukuba (control group), but
      found no significant difference in the UPI scores of the visually impaired and
      the control group. However, we noticed a significant difference in the average
      UPI scores between the hearing impaired and the control group. The visually
      impaired group were divided into four subgroups, UPI scores descended in order
      from degree 1 (total blindness), to degrees 2 and 3 (amblyopia), to degree 4
      (visual acuity > or = 0.3). The UPI scores of the degree 4 subgroup were
      significantly lower than those of the control group. An investigation of the
      items for which the check rate was at least 50% showed that the visually impaired
      students had a variety of psychological problems, most of which seemed to concern
      depression or anxiety as did the normal control group. The number of affirmative
      responses increased with low visual acuity. The only one belonging to the 'lie'
      scale item was observed in the group of hearing impaired students. Thus,
      comparing these three groups from the viewpoint of mental health, we noticed the
      hearing impaired group was slightly different from the other two groups, but the
      visually impaired group was similar to the normal control group.

PMID- 9766691
TI  - Study of the measurement of defense style using Bond's Defense Style
      Questionnaire.
AB  - Two hundred and seventy healthy university students were surveyed in December
      1995 using Bond's Defense Style Questionnaire (DSQ) to measure the subjects'
      defense mechanisms. At the same time, a survey using Byrne's R-S Scale
      (Repression-Sensitization Scale) of the MMPI (Minnesota multiphasic personality
      inventory) and five psychiatric symptom indexes (anxiety, sense of inadequacy,
      sensitivity, depression and impulsive anger) selected from the CMI (Cornell
      Medical Index-Health Questionnaire) was conducted. Three factors were extracted
      from the DSQ through factor analysis: immature defenses, neurotic defenses, and
      mature defenses. The results of analysis of variance revealed the following: (i)
      for anxiety and anxiety related symptoms, both immature defenses and neurotic
      defenses indicated principal effect; (ii) for impulsive anger and depression,
      immature defenses presented principal effect; and (iii) for sensitivity and
      impulsive anger, interaction between a mature defense style and neurotic defense
      style was noted. The relationship between defense styles and psychiatric symptoms
      in healthy people is studied in this paper.

PMID- 9766692
TI  - 'Chiyamai', a panic-like disorder in woman divers from Hegura Island.
AB  - In Hegura Island, Japan, we have recently found female divers who suffer from a
      disorder called 'Chiyamai'. From interviews, questionnaires and temporarily
      proposed diagnostic criteria for Chiyamai, nine cases from 44 female divers
      interviewed, were diagnosed as having Chiyamai. Clinically, Chiyamai is
      characterized by a panic-like attack. Ten symptoms were observed during a panic
      like attack, compared with 13 symptoms in a panic attack described in the DSM-IV.
      The average age at onset was 30 years and the average duration of illness was
      approximately 26 years. Several cases were so severe that the patients were
      unable to continue diving. Additionally, we report a typical case of Chiyamai,
      and discussed the similarities and differences between Chiyamai and anxiety
      disorders in the DSM-IV. We suggest that Chiyamai is a panic-like disorder
      specific to female divers from Hegura Island and that it is a result of heavy
      diving.

PMID- 9766693
TI  - The increasing use of anticonvulsants in prophylactic treatment of bipolar
      disorder.
AB  - The medical records of patents with bipolar disorders who received prophylactic
      drug treatments during three time periods from January 1983 to December 1984,
      January 1988 to December 1989, and from January 1993 to December 1994, were
      reviewed retrospectively. The percentage of lithium monotherapy sharply decreased
      from 96% (51/53) in the first study period to 51.9% (83/160) in the third study
      period. Carbamazepine monotherapy and combination of lithium and carbamazepine
      increased from 3.8% in the first study period to 45.6% in the third study period.
      These results suggest that anticonvulsants may become one of the major drug
      treatment strategies for bipolar disorder in the future.

PMID- 9766694
TI  - The treatment of neuroleptic malignant syndrome using dantrolene sodium.
AB  - The use of dantrolene sodium (DS) in the treatment of neuroleptic malignant
      syndrome (NMS) was studied from the data of 21 cases of NMS, which satisfied the
      diagnostic criteria of Pope et al. The mean dosage of DS was 0.97+/-0.52 mg/kg
      per day and the mean duration of treatment was 8.3+/-5.3 days. It was confirmed
      that the mean duration of treatment with DS tended to be longer in the cases
      involving disturbance of consciousness. However, there were no significant
      differences in the duration of treatment or the mean daily dosage, in the cases
      without disturbance of consciousness regardless of any other complications and
      symptoms. Also, there were no significant differences in the mean duration of
      treatment using DS and the mean dosage of DS between five cases that were
      considered to be 'typical' and 16 cases that were considered to be 'incomplete'.
      In addition, the prognoses of these cases were good such that not even one death
      occurred. In 13 cases, the treatment of psychiatric symptoms with thioridazine
      was started without recurrence of NMS.

PMID- 9766695
TI  - Effects of trazodone hydrochloride and imipramine on polysomnography in healthy
      subjects.
AB  - Polysomnography was performed on eight healthy men with trazodone hydrochloride,
      imipramine and placebo. Trazodone hydrochloride increased slow wave sleep
      significantly. Imipramine prolonged rapid eye movement (REM) latency and
      decreased the percentage of REM sleep significantly. Trazodone decreased stages 1
      and 2 sleep, while imipramine increased it. These findings suggest that the
      antidepressive effect of trazodone might be different from that of imipramine
      with the suppression of REM sleep.

PMID- 9766696
TI  - Neuroleptic-induced Meige's syndrome following akathisia: pharmacologic
      characteristics.
AB  - A 52-year-old schizophrenic patient acutely showed blepharospasm and
      oromandibular dystonia following neuroleptic-induced akathisia. She had suffered
      from schizophrenia and been treated with neuroleptics for 15 years and had
      manifested tardive dyskinesia 5 years ago. Following a change in her neuroleptic
      medication, severe akathisia developed. Two days after the appearance of
      akathisia, blepharospasm and oromandibular dystonia appeared. After the
      disappearance of akathisia, the disorder continued. The frequency of
      blepharospasm ranged from 30 to 40 (times/min). The oral administration of
      trihexyphenidyl (6 mg/day), perphenazine (12 mg/day), and fluphenazine (12
      mg/day) significantly decreased the frequency of blepharospasm, whereas
      carbamazepine (600 mg/day) and sulpiride (1200 mg/day) did not. These results
      suggest that overactivity of both cholinergic and dopaminergic functions in the
      striatum may be involved in this patient. Our patient, who showed acute onset of
      Meige's syndrome following neuroleptic-induced akathisia, is of interest to those
      studying the pathogenesis of Meige's syndrome.

PMID- 9766697
TI  - Severe chronic active Epstein-Barr virus infection accompanied by virus
      associated hemophagocytic syndrome, cerebellar ataxia and encephalitis.
AB  - We present a rare case of chronic active Epstein-Barr virus (EBV) infection
      showing various clinical outcomes. A 26-year-old man was admitted to our hospital
      due to persistent fever and dyspnea. Serologic response of the patient to EBV
      indicated chronic active infection. He showed pleuritis, parotitis, chronic
      hepatic dysfunction, disseminated intravascular coagulation, virus associated
      hemophaghocytic syndrome, acute rhabdomyolysis, acute renal failure, acute
      cerebellar ataxia, encephalitis and multiple brain abscesses. None of acyclovir,
      gancyclovir, prednisolone or interleukin-2 was effectual to abolish those
      abnormalities. This is the first report of transient cerebellar ataxia which
      aggravated to panencephalitis associated with chronic EBV infection.

PMID- 9766698
TI  - Further characterization of the 5'-flanking promoter region of the human beta1
      adrenergic receptor gene.
AB  - Further characterization of the 5'-flanking promoter region of the human beta1
      adrenergic receptor (AR) gene was attempted. The transcription initiation sites,
      determined by the primer extension and the rapid amplification of the 5'-cDNA
      end, are multiple in a spanning about 30 nucleotides (-289 to -261 relative to
      the translation start site). There exist inverted CCAAT boxes, multiple binding
      sites for transcription factor Sp1 and AP-2 nearby transcription initiation
      sites, however, this region lacks a typical TATA box. In order to localize the
      regulatory region for the basal transcription of the human beta1-AR gene, a
      variety of 5'-flanking sequence/chloramphenicol acetyltransferase reporter gene
      fusion constructs was prepared and transiently expressed in HeLa cells.
      Functional analyses reveal negatively (-3813 to -2925 and -1772 to -796) as well
      as positively (-2925 to -1772) regulatory regions, in addition to the region (
      796 to -87) being necessary for the basic expression of the human beta1-AR gene.

PMID- 9766699
TI  - Anticonvulsant effects of dipotassium clorazepate on hippocampal kindled seizures
      in rats.
AB  - We examined the anticonvulsant properties of dipotassium clorazepate (DC) against
      hippocampal kindled seizures in rats. Adult male Wistar rats were subjected to
      kindling 1 week after the implantation of electrodes. After five stage 5 seizures
      were induced, the generalized convulsion triggering threshold (GST) was
      determined. Dipotassium clorazepate was administered intraperitoneally in rats
      that showed two stable stage 5 seizures induced at the GST current intensity.
      Dipotassium clorazepate at doses of 1 mg/kg or more produced an anticonvulsant
      effect, but did not readily suppress limbic seizures. Dipotassium clorazepate did
      not completely suppress after-discharges (AD) even at the highest dose, which was
      5 mg/kg. Moreover, raised stimulus intensity failed to affect its efficacy as an
      anticonvulsant. The results of the present study suggest that DC has a modest
      anticonvulsant potency. It is reasonable to assume that its anticonvulsant
      efficacy is primarily due to attenuation of AD propagation rather than the
      raising of the seizure triggering threshold at the kindling focus.

PMID- 9766700
TI  - Depression among caregivers of the elderly in need of care and their service
      utilization: a pilot study.
AB  - Twenty-four community residing elderly people in need of care, who were
      registered with the municipal welfare center in Miyagi Prefecture, Japan, and
      their principal caregivers participated in the study. The principal caregivers
      completed a self-administered questionnaire involving their demographic status,
      provided data on their utilization of formal services and completed the Center
      for Epidemiologic Studies Depression Scale (CES-D). The health visitors examined
      the activities of daily living (ADL) and mental status of these 24 elderly
      individuals. More than half the caregivers appeared to be depressed. The non
      depressed caregivers used significantly more services than the depressed
      caregivers even after the caregivers' age was statistically controlled.

PMID- 9766701
TI  - The search for novel antiarrhythmic strategies. Sicilian Gambit.
AB  - The past fifty years of antiarrhythmic drug development have seen limited success
      in prolonging life and reducing morbidity. It is likely that arrhythmias are in
      most instances final common pathways through which changes in the cardiac
      substrate and in trigger mechanisms are expressed. We propose that the
      development and administration of therapies for the arrhythmias themselves, while
      offering a panacea for a disease entity that has evolved and is being overtly
      manifested, is also an admission of failure to identify and prevent evolution of
      the substrate and triggers such that arrhythmias can occur. We suggest that while
      strategies for treatment and prevention of recurrence of arrhythmias still
      warrant exploration, greater hope for the future lies in identifying means for
      earlier diagnosis of the arrhythmogenic substrate and triggers, and in developing
      therapies that are "upstream" to the arrhythmia and prevent their initial
      expression. Means to achieve this end are suggested, using specific arrhythmias
      as examples. Similarly, to increase the likelihood that clinical studies of new
      therapies can be successfully concluded and interpreted, we suggest new
      approaches to patient selection, risk stratification, trial endpoints, outcome
      events and trial methodologies.

PMID- 9766702
TI  - Skeletal muscle deoxygenation during exercise assessed by near-infrared
      spectroscopy and its relation to expired gas analysis parameters.
AB  - The present study was performed to determine the relation between oxygenated
      hemoglobin (oxy-Hb) changes in working muscles and ventilatory parameters. Six
      active normal subjects, 21 sedentary normal subjects and 16 patients with heart
      failure performed an incremental exercise with expired gas analysis.
      Deoxygenation of the vastus lateralis muscle was monitored for oxy-Hb changes
      using near-infrared spectroscopy. Near the anaerobic threshold (AT), oxy-Hb
      started to decrease, forming the first inflection point (P1). Near the
      respiratory compensation point (RCP), the second inflection point (P2) was
      observed. Oxygen uptake at the AT, RCP, P1 and P2 decreased in magnitude first in
      the active normal subjects, then in sedentary normal subjects and finally in the
      heart failure patients. High correlation was demonstrated between AT and P1
      (r=0.8, p<0.0005) and between RCP and P2 (r=0.9, p<0.0005). In 12 sedentary
      normal subjects who underwent repeat exercise, reproducibility was confirmed for
      both P1 and P2. Constant work rate exercises were performed in 5 sedentary normal
      subjects, and in all of them the oxy-Hb remained unchanged below the AT work
      rate, whereas oxy-Hb decreased above the AT work rate. Exercise capacity, with
      respect to both working muscle deoxygenation and ventilation, could be evaluated
      in detail by the concomitant use of near-infrared spectroscopy and expired gas
      analysis.

PMID- 9766703
TI  - Influence of aerobic exercise training on brain natriuretic peptide secretion in
      patients in the chronic phase of myocardial infarction.
AB  - Brain natriuretic peptide (BNP) secretion increases after myocardial infarction
      (MI); its plasma level may reflect the degree of left ventricular dysfunction.
      This study examines how aerobic exercise therapy for MI influences BNP secretion.
      Subjects included 70 patients (mean age, 62.0+/-11.3 years) who were divided into
      four groups: (1) 20 patients with an anterior MI and exercise training; (2) 20
      patients with an anterior MI and no exercise training; (3) 15 patients with an
      inferior MI and exercise training; and (4) 15 patients with an inferior MI and no
      exercise training. The training groups performed aerobic exercise 3 times a week
      for 2 months. Exercise intensity was defined as a heart rate of anaerobic
      threshold (AT), derived from the treadmill cardiopulmonary exercise testing at 1
      month after the onset of MI. The subjects underwent cardiopulmonary exercise
      testing again at 3 months after the onset of MI. To measure BNP, blood samples
      were obtained in the resting state and immediately after the peak exercise. AT
      and peak oxygen uptake increased in the training group with anterior MI and in
      both the training and nontraining groups with inferior MI. Significant serial
      change in plasma BNP level was not observed in the inferior MI groups. Plasma BNP
      level decreased longitudinally only in the nontraining anterior MI group. It was
      concluded that exercise training in patients with an anterior MI could delay the
      recovery of left ventricular function, but will increase exercise tolerance.

PMID- 9766704
TI  - Impact of percutaneous transluminal coronary angioplasty on coronary bypass
      surgery--changes in the patient profile during the past decade.
AB  - As percutaneous transluminal coronary angioplasty has become an increasingly
      common procedure replacing coronary artery bypass grafting (CABG), the clinical
      profile of the patients referred for CABG has changed markedly. A retrospective
      study of the changes in the clinical profile and surgical outcome of patients who
      underwent CABG during the past 10 years was conducted. Between March 1982 and
      February 1996, 1010 patients underwent isolated CABG at Nara Medical University.
      The first 100 consecutive patients who underwent CABG in 1984-85 (group 1) were
      compared with the first 100 consecutive patients who underwent CABG in 1994-95
      (group 2). Preoperative risk increased significantly during the decade with
      respect to patient age (p<0.001), the presence of diabetes mellitus (p=0.048),
      the number of diseased vessels (p<0.001), left main trunk disease (p=0.008), the
      presence of aortic or peripheral vascular disease (p=0.032),and the need for
      emergency surgery (p=0.013). Operative procedures have become more complicated
      with respect to the number of total and arterial grafts, duration of the aortic
      cross-clamp and cardiopulmonary bypass. Hospital mortality for elective CABG has
      not changed (2%) and the overall mortality has not increased significantly (from
      2% to 3%) during the decade. In conclusion, although the preoperative risks have
      increased and more complicated procedures are required, CABG continues to be
      performed safely with low mortality rates.

PMID- 9766705
TI  - Head-up tilt test combined with isoproterenol infusion provokes coronary
      vasospastic angina.
AB  - The association of the autonomic nervous system with coronary vasospasm has been
      controversial. The aim of the present study was to examine the involvement of the
      autonomic nervous system in coronary vasospasm by applying the head-up tilt (HUT)
      test to patients with coronary vasospastic angina. Fifteen consecutive patients
      with coronary vasospastic angina and without significant organic coronary
      stenoses underwent the HUT test. Prior to the test, coronary spasm was documented
      angiographically by using an intracoronary injection of acetylcholine or
      ergonovine. The HUT test was performed in the early morning and repeated in the
      afternoon if the test was positive in provoking angina pectoris and syncope or
      presyncope. If the test was negative, it was repeated under intravenous infusion
      of isoproterenol at a rate of 1-2 microg/min. The HUT test under isoproterenol
      infusion in the morning provoked vasospastic angina with syncope or presyncope in
      9 of the 15 patients. In the test-positive group, heart rate was significantly
      reduced (104+/-17 beats/min to 84+/-25 beats/min, p<0.05), which preceded a
      reduction in systolic blood pressure (158+/-25 mmHg to 125+/-17 mmHg, p<0.001),
      angina attack and syncope. The HUT test without isoproterenol infusion in the
      morning and the HUT test in the afternoon with or without isoproterenol infusion
      failed to provoke angina. The heart rate reduction preceding reduced systemic
      blood pressure and anginal attack suggested that parasympathetic nerve excitation
      plays an important role in coronary vasospasm. The results also implied that the
      HUT test combined with isoproterenol infusion is useful for the provocation of
      coronary spasm.

PMID- 9766706
TI  - Changes of ischemic heart disease in Utsunomiya, Japan, over 10 years: a survey
      of primary care physicians.
AB  - A total of 502 patients presenting in Utsunomiya city and its suburbs during a 10
      year period were studied to determine the clinical features of ischemic heart
      disease and to identify coronary risk factors. The male/female ratio was 1.21,
      but the ratio decreased with increasing age. The duration of chest pain showed a
      continuous spectrum between angina and infarction, with a short duration of chest
      pain not being useful for excluding the diagnosis of myocardial infarction.
      Hypertension was more common than hypercholesterolemia in this study, although
      the prevalence of the latter increased slightly with time, along with the shift
      towards a modernized occupational pattern. Smoking was a more important risk
      factor for ischemic heart disease in younger individuals than in the elderly, and
      diabetes mellitus was highly associated with the development of myocardial
      infarction. The incidence of radiologically diagnosed cardiac hypertrophy and
      aortic calcification decreased over time. These changes may have resulted in part
      from improved blood pressure control and the development of new anti-hypertensive
      and cholesterol-lowering agents.

PMID- 9766708
TI  - Percutaneous revascularization of lesions with saphenous vein graft failure:
      influence of chronic total occlusion on early outcome.
AB  - The purpose of this study was to evaluate a therapeutic strategy of percutaneous
      transluminal coronary angioplasty (PTCA) in patients with recurrent angina
      following coronary artery bypass grafting. The study looked at 112 branches
      associated with graft failure, excluding new lesions in the native coronary
      artery (NCA). Chronic total occlusion (CTO) was observed in 50% of NCA (56/112)
      and in 68% of the grafts (76/112). Thirty-three branches (29%) showed CTO in both
      NCA and the graft. The overall success rate was 86% (96/112). The success rate on
      NCA was 98% (44/45) in non-CTO, while in CTO it was significantly lower at 62%
      (18/29). As to grafts, the success rate was 94% (32/34) in non-CTO, while it was
      50% (2/4) in CTO. These characteristics, with respect to lesion morphology and
      the prevalence of CTO, exerted an influence on the selection of the access
      vessels for revascularization. Early outcome depended on the result of treatment
      of CTO.

PMID- 9766707
TI  - Effect of chronic neutral endopeptidase inhibition on cardiac hypertrophy after
      experimental myocardial infarction.
AB  - Candoxatril is an inhibitor of neutral endopeptidase, a membrane-bound enzyme
      that degrades atrial natriuretic peptide. The effects of candoxatril on
      hemodynamic parameters and cardiovascular hypertrophy were evaluated in the rat
      model of myocardial infarction. Myocardial infarction was induced by left
      coronary artery ligation in rats and they were treated either with candoxatril
      (10mg/kg per day) or a vehicle for up to 4 weeks. Systolic blood pressure and
      body weight did not change for up to 4 weeks between the 2 groups. At the end of
      treatment, hemodynamic parameters were measured, and then plasma, heart, lungs
      and kidneys were collected. Kidney neutral endopeptidase, as measured by the
      quantitative autoradiographic method, was significantly inhibited in candoxatril
      treated rats compared with that in controls (66.6+/-3.2% of control, p<0.001). On
      the contrary, there were no significant differences in right atrial pressure,
      left ventricular end-diastolic pressure, systemic pressure, and plasma level of
      atrial natriuretic peptide between the 2 groups. There were also no significant
      differences in cardiac weight and lung weight. These data indicate that
      inhibition of neutral endopeptidase by candoxatril at a dose of 10 mg/kg per day
      did not oppose cardiac hypertrophy in the rat model of myocardial infarction in
      spite of significant neutral endopeptidase inhibition.

PMID- 9766709
TI  - Chronic degenerative changes in the myocardium supplied by bridged coronary
      arteries in eight postmortem samples.
AB  - In humans, the coronary arteries course not only subepicardially but also
      intramyocardially. The intramyocardial course of the coronary artery is reported
      to lead to acute ischemic heart disease and, as well, it may be symptomless. The
      aim of this study was to investigate the long-term ischemic effects of bridged
      arteries on the myocardium, and was carried out on 8 autopsy hearts with
      myocardial bridges and 2 hearts without myocardial bridges. The samples from the
      myocardium were examined with light microscopy. In the myocardium supplied by the
      bridged arteries, it was observed that there was an increase in the intercellular
      connective tissue, which was rich in collagen bundles, lymphocytes, fibroblasts
      and macrophages. Compression of the coronary artery by myocardial bridges may
      cause chronic degenerative changes, which may remain silent for a long time.

PMID- 9766711
TI  - Surgical treatment for Scheie's syndrome (mucopolysaccharidosis type I-S): report
      of two cases.
AB  - Scheie's syndrome (mucopolysaccharidosis type I-S) is a rare genetic lysosomal
      storage disease affecting mucopolysaccharide metabolism, and is known to include
      cardiovascular disease. Surgical treatment was carried out in 2 patients with
      Scheie's syndrome. Patient 1 was a 56-year-old man with triple-vessel coronary
      artery disease, who successfully underwent coronary artery bypass grafting.
      Patient 2 was a 52-year-old man with aortic and mitral valve stenosis, who
      successfully underwent combined aortic and mitral valve replacement. The
      literature on Scheie's syndrome associated with valvular and coronary artery
      disease is also reviewed.

PMID- 9766710
TI  - Cell cycle of myocytes of cardiac and skeletal muscle in mitochondrial myopathy.
AB  - Patients who have mitochondrial myopathy can present with specific pathological
      conditions (eg, diabetes mellitus and deafness). A 36-year-old woman presented
      with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like
      episodes (MELAS). An investigation was conducted into whether the abnormalitiy of
      mitochondrial DNA (a T to C transition at position 3271 in the mitochondrial tRNA
      [Leu(UUR)] gene) influences nuclear DNA synthesis by cells in the heart, skeletal
      muscles, and brain. Myocardium, skeletal muscle, and brain tissues were stained
      with hematoxylin-eosin, and Masson trichrome for histopathology. Target nuclei
      taken from the myocardial and skeletal muscles and brain tissue were purified
      after removing debris by the modified Hedley method. These nuclei were stained
      with propidium iodide (PI) for analysis by flow cytometry. The number of nuclei
      in the G2M phase was bigger in myocytes of MELAS than in normal myocytes
      (Control) (MELAS myocyte: Control myocyte=24.9+/-7.3: 6.1+/-1.6%, p<0.005), but
      there was no significant increase in the G2M phase in brain tissue. The G1 phase
      was far more reduced in MELAS myocytes and skeletal muscle than in Controls
      (MELAS myocyte: Control myocyte=65.8+/-9.1: 88.0+/-3.2%, p<0.005; MELAS skeletal
      muscle: Control skeletal muscle=85.1+/-2.2: 90.1+/-3.2%, p<0.05), while there was
      no significant decrease of nuclei in the G1 phase in brain tissue. Increased
      amount of nuclei in the G2M phase in cardiac myocytes and skeletal muscle cells
      compared with that in neurons might depend on the capacity for proliferation and
      differentiation of these cells as compared with brain tissue. It was concluded
      that the mitochondrial DNA mutation (3271T-to-C) of MELAS may influence the
      nuclear DNA synthesis of cells in various tissues depending on their level of
      mitotic activity.

PMID- 9766712
TI  - Left coronary artery-left ventricle fistula with right coronary artery spasm.
AB  - A 72-year-old woman was admitted to our hospital for evaluation of chest pain.
      Coronary angiography showed a left coronary artery-left ventricle fistula. An
      acetylcholine provocation test induced vasoconstriction of the right but not the
      left coronary artery. Her chest pain was not relieved by combined therapy with
      isosorbide dinitrate, diltiazem and nicorandil. Because of the coronary spasm,
      beta-blockers could not be used. However, her chest pain was relieved after the
      administration of a minor tranquilizer. Thus, the patient's chest pain was
      unlikely to be associated with either the fistula or the coronary spasm.

PMID- 9766713
TI  - Effect of relatively low dose amiodarone therapy on left ventricular function in
      patients with ventricular tachyarrhythmias.
AB  - The effect of oral amiodarone (AMD) therapy on left ventricular (LV) function was
      evaluated retrospectively in Japanese patients with ventricular tachyarrhythmias
      and congestive heart failure. Seventeen patients were treated with oral AMD
      (maintenance dose 191+/-52mg/day) for more than 12 months. Fractional shortening
      (FS) on echocardiography revealed a trend towards an increase in the short-term
      (3 months) (p=0.06), but was not significant in the long-term follow-up period
      (more than 12 months) after AMD therapy. In 8 patients with 1 episode of
      myocardial infarction, FS revealed a trend towards an increase (p=0.09). In all
      of the 4 patients with dilated cardiomyopathy whose LV end-diastolic diameter was
      increased, FS was decreased in the long-term follow-up. Neither hospitalization
      frequency nor New York Heart Association classification were reduced by AMD
      therapy. In conclusion,oral AMD therapy did not cause LV function to recover
      significantly and could not improve the clinical course in patients with
      ventricular tachyarrhythmias. However, if the underlying disease is not
      progressive, AMD therapy may improve LV function.

PMID- 9766714
TI  - Simultaneous elevation of the levels of circulating monocyte chemoattractant
      protein-1 and tissue factor in acute coronary syndromes.
AB  - The levels of circulating monocyte chemoattractant protein-1 (MCP-1) and tissue
      factor (TF) were examined on admission in 46 consecutive patients with acute
      coronary syndromes (ACS) and 30 patients with stable exertional angina (SEA). The
      plasma levels of both MCP-1 and TF were higher in the ACS patients than in the
      SEA patients (MCP-1: p<0.001; TF: p<0.001). Only the circulating TF level related
      to the number of diseased vessels. A positive correlation between plasma MCP-1
      and TF levels was found (r=0.476, p<0.001). These results suggest that
      circulating MCP-1 plays an important role in the pathogenesis and/or development
      of ACS.

PMID- 9766715
TI  - Fibrinolytic treatment of pleural infection.

PMID- 9766717
TI  - Imaging of acute right lower abdominal quadrant pain.
AB  - This article reviews the clinical diagnosis of appendicitis, indications and
      options for appendiceal imaging, compares appendiceal CT techniques, and
      describes the imaging findings with appendicitis and alternative conditions that
      can clinically mimic appendicitis.

PMID- 9766716
TI  - Imaging the thyroid.
AB  - Thyroid imaging has historically relied heavily on scintigraphy, although, not
      surprisingly in view of the superficial position of the gland, ultrasound has
      assumed an increasingly prominent role in recent years. The other cross-sectional
      imaging modalities can also be useful, and the emergence of new
      radiopharmaceuticals and the increasingly central role of fine needle aspiration
      cytology have further added to the range of diagnostic techniques available. This
      review attempts to summarize the current state of knowledge, and makes some
      suggestions for the most efficient use of imaging resources in the investigation
      of thyroid disease.

PMID- 9766718
TI  - Functional endoscopic sinus surgery (FESS): what radiologists need to know.
AB  - The place of coronal computed tomography (CT) in the assessment of patients prior
      to functional endoscopic sinus surgery (FESS) is well established. The ability to
      accurately correlate radiological and surgical anatomy enhances precision and
      safety during FESS. This pictorial essay reviews the conceptual anatomical
      framework that forms the basis of FESS.

PMID- 9766720
TI  - The clinical effectiveness of the Gianturco oesophageal stent in malignant
      oesophageal obstruction.
AB  - Between January 1994 and December 1996 72 patients were treated with 76 Gianturco
      oesophageal stents for oesophageal obstruction or perforation. The patients were
      followed prospectively in order to determine the effectiveness in improving
      dysphagia, to establish long term patency, survival times and complications. The
      mean dysphagia score prior to stenting was 3, improving to a mean score of 1
      after stenting. Swallowing failed to improve in three patients. No serious
      complications were seen at stent insertion. Patients tolerated the procedure well
      with no complications in 63%. The most frequent immediate complication was chest
      pain occurring in 15 patients (21%). This settled in all patients with
      appropriate analgesia, however, four patients required long-term pain relief. In
      no cases was the chest pain due to perforation. Re-intervention was required in
      16.7% of patients, the commonest cause being tumour overgrowth, and this was seen
      primarily in patients with long survival. The migration rate was low, despite the
      fact that 45 of 76 stents had been placed with the distal end in the stomach.
      Only four stents (5.6%) migrated completely, all of which had been deployed
      across the cardia. In our series the use of the Gianturco oesophageal stents for
      provided effective palliation of malignant oesophageal obstruction.

PMID- 9766719
TI  - Computed tomography and positron emission tomography in the pre-operative staging
      of oesophageal carcinoma.
AB  - Because patients with carcinoma of the oesophagus usually present with advanced
      disease and surgery has a high mortality with cure in less than 10% of patients,
      pre-operative staging to select appropriate patients is necessary. Computed
      tomography (CT) plays an important role in staging but has well recognized
      limitations. Positron emission tomography (PET) which provides physiological
      information may therefore be a better alternative. OBJECTIVE: To compare the
      findings of CT and positron emission tomography (PET) with 2-[18fluorine]-fluoro
      2-deoxy-D-glucose (FDG) in the pre-operative staging of oesophageal carcinoma.
      MATERIALS AND METHODS: Twenty-five patients with biopsy proven oesophageal cancer
      had pre-operative staging using CT and FDG-PET. The studies were read
      independently and full histological confirmation was obtained in 19 patients.
      Four parameters were studied: the primary tumour, peri-oesophageal lymph nodes,
      liver metastases and left gastric lymph nodes. RESULTS: PET visualized all
      primary tumours; CT missed one. CT identified 4/8 patients with involved peri
      oesophageal nodes and PET 3/8. CT identified 5/9 patients with left gastric
      adenopathy and PET 1/9. PET visualized a liver metastasis missed on CT and
      appeared to be better in assessing residual tumour. PET did identify distant
      metastases not seen on CT in seven patients. CONCLUSIONS: The two techniques are
      both effective in showing the primary tumour and about equally sensitive in the
      demonstration of peri-oesophageal nodes. PET is probably more sensitive than CT
      for the detection of distant metastases.

PMID- 9766722
TI  - Rotational digital subtraction carotid angiography: technique and comparison with
      static digital subtraction angiography.
AB  - Recent advances in angiography equipment have allowed the development of
      rotational digital subtraction carotid angiography. We give the first description
      of this technique applied to the extracranial carotid circulation, using the
      Phillips Integris V3000 release 11. Forty-three patients undergoing conventional
      digital subtraction angiography were compared with 63 patients who had rotational
      digital subtraction angiography for examination of the extracranial carotid
      circulation. The parameters compared were: total procedure time, volume of
      contrast injection, number of contrast injections, total data acquisition time,
      image quality, radiation dose and patient comfort. There was a reduction in the
      total procedure time, improvement in patient comfort, data acquisition time and a
      reduction in the number of injections. Conventional DSA may underestimate
      stenoses in 65% of cases. There is no significant change in the total volume of
      contrast injected. There is, however, an increase in the radiation dose during
      data acquisition.

PMID- 9766721
TI  - Magnetic resonance imaging of prostate cancer: comparison of image quality using
      endorectal and pelvic phased array coils.
AB  - OBJECTIVE: To compare endorectal coil (ERC) and pelvic phased array (PPA) coil
      magnetic resonance imaging for delineation of the prostate gland and seminal
      vesicles. To compare ERC images at different inflation volumes of the ERC air
      balloon. MATERIALS AND METHODS: Twenty-one patients underwent T2-weighted
      examinations using PPA and ERC. The ERC evaluations were performed at three
      balloon inflation volumes (60, 100 and 140 ml). All patients had proven prostate
      cancer. Images were analysed for visibility of anatomic structures, gland
      distortion, tumour visualization, artefacts (coil flare, coil-related artefact
      and rectal movement) and overall image quality. A grading system was used for
      each parameter. RESULTS: ERC assessments at increasing balloon inflations showed
      equivalent anatomical detail and overall image quality. However, increasing gland
      distortion and decreasing coil related flare was found with higher air inflations
      (P = 0.13 and P = 0.006, respectively). When compared with ERC images, visibility
      of the anterior gland and neurovascular bundles was better with the PPA coil (P =
      0.0001 and 0.002, respectively). The overall image quality was superior with the
      PPA coil (P = 0.0001). However, no significant difference in visualization of
      tumour or delineation of tumour extent was observed between the two techniques.
      CONCLUSIONS: PPA imaging of the prostate gland provides images of superior
      quality compared with the ERC. This is mainly due to fewer artefacts with the PPA
      coil and improved anterior gland visibility. When ERC is used, air inflation to
      at least 100 ml reduces coil flare artefact.

PMID- 9766723
TI  - The therapeutic impact of lumbar spine MRI on patients with low back and leg
      pain.
AB  - The influence of lumbar spine magnetic resonance imaging (MRI) on the management
      of patients with low back and leg pain, with a clinical diagnosis of neural
      compression, has been investigated by a controlled prospective observational
      study. The clinical features of the patients at the time of request for MRI have
      been compared with the subsequent management in order to define the clinical
      indications for lumbar spine MRI. METHODS: Clinical history, physical examination
      findings and tests of functional and psychological disability were all recorded
      at the time of request for MRI. Following MRI, patients were assessed without
      knowledge of the MRI findings and a diagnosis and management plan recorded.
      Immediate access to the MRI report and hard copy films was then provided and a
      revised diagnosis and management plan made. The clinical features and MRI
      findings were compared with the subsequent management. RESULTS: Seventy-two
      patients were examined, 65 (90.3%) had leg pain as a predominant feature and
      abnormalities in neurological examination were found in 31 (43%). Twenty-three of
      48 (47.9%) of patients with a pre MRI management plan of surgery were changed to
      conservative management following the MRI. The diagnosis altered in 50 % of cases
      with the largest change in diagnosis occurring in 13 patients where MRI did not
      confirm the clinical impression of nerve root compression. Seventeen patients
      with no abnormality of neurological testing were subsequently treated by surgery
      which included all 12 patients treated by spinal fusion. CONCLUSIONS: The major
      impact of MRI was to move patients towards conservative treatment. A variety of
      features in the history and physical examination as well as MRI findings are
      predictors for surgical treatment. The variety of diagnoses and surgical options
      available make it difficult to define clear clinical guidelines for the use of
      MRI.

PMID- 9766724
TI  - Acute right ventricular dilatation: a new helical CT sign of massive pulmonary
      embolism.
AB  - Acute right heart failure is a principal cause of circulatory collapse and death
      in patients with massive pulmonary embolism (PE). The purpose of this study was
      to investigate if helical computed tomography (CT) could contribute to the
      assessment of the right ventricle (RV) in those with massive PE. Over an 8-month
      period 79 helical CT pulmonary angiograms were performed to investigate suspected
      PE. Emboli were demonstrated in 28 (35%) patients and seven (9%) were considered
      to have had a major thromboembolic event. The CT scans of all patients were
      evaluated using parameters derived in the axial plane (maximum minor axis RV and
      LV dimensions, RV:LV minor axis ratio and RV wall thickness). Acute right
      ventricular dilatation with an RV:LV ratio> 1.5:1 (range 1.6:1-2.3:1, mean 2:1)
      was found in all seven patients who had sustained major PE. In the remaining
      group of 21 with lesser degrees of embolism no patient had an RV:LV ratio > 1.1:1
      (range 0.8-1.1, mean 1.0). To our knowledge, this CT sign has not been described
      before. CONCLUSION: Helical CT can identify acute RV dilatation in addition to
      making the primary diagnosis in patients with massive PE. This observation may
      help identify those at greatest risk of a second fatal event and facilitate
      therapeutic strategy.

PMID- 9766725
TI  - Hepatic malignant fibrous histiocytoma: CT findings.
AB  - Although malignant fibrous histiocytoma represents the most common soft tissue
      sarcoma in adults, its origination in visceral organs is very unusual and the
      liver is an exceptional site of involvement, with only 22 cases reported in the
      last 12 years. This controversial tumour, first described in 1964, probably
      originates from undifferentiated mesenchymal cells and has five different
      histological subtypes: storiform pleomorphic, myxoid, giant cells, inflammatory
      and angiomatoid. We describe herein the rather variable CT findings of three
      malignant fibrous histiocytomas of the liver and discuss their differential
      diagnosis.

PMID- 9766726
TI  - Azygos reflux: a CT sign of cardiac tamponade.
AB  - Three patients who were investigated with dynamic contrast medium enhanced
      computed tomography (CT) of the thorax were noted to have pericardial effusions
      with reflux of contrast medium back along the azygos vein. The diagnosis of
      cardiac tamponade was not made clinically, but in each case was suggested from
      the CT findings. Confirmation of the diagnosis was made in all three cases, two
      patients with echocardiography and one at post mortem. One patient made a rapid
      recovery following the insertion of a pericardial drain, another made a temporary
      recovery after pericardiocentesis but the third died. Thirty CT scans performed
      with similar protocol were reviewed and none of these demonstrated reflux along
      the azygos vein. The presence of contrast medium refluxing into the azygos vein
      implies significant haemodynamic disturbance, and in the presence of a
      pericardial effusion suggests the diagnosis of cardiac tamponade.

PMID- 9766727
TI  - Case report: Radiolabelled octreotide scanning as a guide to the management of an
      occult carcinoid tumour.

PMID- 9766728
TI  - Case report: Small intestinal pseudo-obstruction: an unusual manifestation of
      polymyositis.

PMID- 9766729
TI  - Radiological investigation of suspected lower limb deep vein thrombosis.

PMID- 9766730
TI  - Radiological investigation of suspected lower limb deep vein thrombosis.

PMID- 9766731
TI  - Malfunctioning central venous catheters.

PMID- 9766732
TI  - Transthoracic needle biopsy.

PMID- 9766733
TI  - But what can you do for them?

PMID- 9766734
TI  - Growth of preterm infants with cystic periventricular leukomalacia.
AB  - Etiology of the high rates of growth failure in children with cerebral palsy (CP)
      remains unclear. The purpose of this study was to evaluate the relation between
      growth failure in preterm infants with cystic periventricular leukomalacia (CPVL)
      and neonatal health complications. The population consisted of all preterm
      infants (51) with a gestational age of <33 weeks who were admitted to the
      Children's Hospital of Buffalo from 1988 to 1993 and who had CPVL. Out of the 41
      survivors with CPVL who were followed, 39 developed CP and 18 developed growth
      failure during infancy. At the time of greatest growth failure, the majority
      (72%) of infants had signs of undernutrition as defined by the Waterlow (1972)
      classification. Oral feeding impairment was the sole risk factor for the
      occurrence of growth failure. Undernutrition appears to be important in the
      occurrence of growth failure in preterm infants with CPVL and CP.

PMID- 9766736
TI  - Sleep EEG and developmental dysphasia.
AB  - To determine the relation between developmental dysphasia and EEG anomalies
      during sleep, we compared 52 subjects with dysphasia with a control group of 20
      children by using the ambulatory EEG method. Whereas 50% of the children with
      dysphasia experienced paroxysmal activity (PA), only two of the control group
      did. It is likely that paroxysmal abnormalities and language impairment are
      related to architectural dysplasia and neuron-migration disturbances. PA is
      frequent in subjects with receptive developmental dysphasia and may be the cause
      of language deterioration. When the occurrence of paroxysmal abnormalities during
      sleep is higher than 8% of total sleep time, we suggest the use of antiepileptic
      drugs.

PMID- 9766735
TI  - Gangliosides in cerebrospinal fluid in children with autism spectrum disorders.
AB  - Gangliosides are sialic acid-containing glycolipids found in all cells,
      especially abundant in nerve cells and mainly situated on outer-membrane
      surfaces. The aim of this study was to provide data on the concentration of
      gangliosides in the CSF of children and adolescents with autism spectrum
      disorders (ASD) - 66 with autistic disorder, and 19 with other autism spectrum
      disorders. The comparison group consisted of 29 children and adolescents, whose
      CSF had been sampled to exclude acute infectious CNS disorder. The concentrations
      of the gangliosides GM1, GD1a, GD1b, and GT1b were determined using a
      microimmunoaffinity technique. The ASD group had a significantly higher
      concentration of ganglioside GM1 compared with the comparison group. The GM1
      increase could not be explained as secondary to other clinical factors. Mean
      ganglioside levels did not differentiate subgroups with autistic disorder and
      those with a more atypical clinical picture, nor subgroups with known medical
      disorders and those with idiopathic autism. Altered patterns of gangliosides in
      the CNS might reflect important correlates of pathogenesis in autism.

PMID- 9766737
TI  - Do hyperactive children have motor organization and/or execution deficits?
AB  - Hyperactive children have been described as motorically clumsy. To explore the
      validity of this assertion, an experiment using the additive factor method was
      designed to examine motor organization and execution in hyperactive children.
      Four groups of boys aged 7 to 8 years took part in the study: (1) a pure
      hyperactive (HA) group, N=20; (2) a pure conduct-disordered (CD) group, N=18; (3)
      a mixed hyperactive/conduct-disordered (HA+CD) group, N=12; (4) a normal (N)
      control group, N=22. While the small sample size precluded a definitive
      conclusion, the results indicated that neither HA nor CD children showed any
      motor organization or execution deficit in a simple sequential key-tapping task.
      Given previous findings indicating that hyperactive children show deficits in
      more complex motor coordination skills, the generalizability of our negative
      results needs to be examined on other more complex tasks.

PMID- 9766738
TI  - Aetiological factors and prevalence of severe mental retardation in children in a
      Swedish municipality: the possible role of consanguinity.
AB  - The prevalence of severe mental retardation (SMR) was studied in one of the 24
      suburban municipalities in Stockholm. The study area had a high proportion of non
      European nationals. The study population comprised 14138 children born between
      1979 and 1992 who resided in this municipality on the census day, 31 December
      1995. The total prevalence of SMR was 4.5 per 1000, being 3.7 per 1000 and 5.9
      per 1000 in the European and in the non-European population, respectively. The
      majority of cases (66%) had a definite prenatal origin. Down syndrome was the
      cause in 20%. Six families (10%) had at least two children with SMR. It was
      concluded that the prevalence was higher than in previous Swedish studies. Many
      cases were attributed to genetic factors. Consanguineous marriages were assumed
      to be a factor of importance in the distribution of aetiologies. Demographic
      differences between areas in Sweden must be considered when planning habilitation
      services.

PMID- 9766739
TI  - Hand function in children with cerebral palsy after upper-limb tendon transfer
      and muscle release.
AB  - Thirty-two children with hand dysfunction due to cerebral palsy were examined
      before tendon transfer and muscle release, and 9 months postoperatively. All
      children improved their performance regardless of the degree of impaired hand
      function. The main advantage of surgery was a more functional position of the
      hand with increased wrist extension and forearm supination. There were also
      increased functionality of handgrips, grip strength, and dexterity. Impaired
      sensibility before surgery did not influence the outcome. Individual goals were
      set preoperatively. Individual functional goals outlined before surgery were met
      by most children. Children identified as having mild impairments gained new
      functional skills related to everyday activity (self-care and leisure), while
      children with severely impaired hand function demonstrated enhanced grasping
      ability, as well as a better cosmetic appearance.

PMID- 9766741
TI  - Saccadic strategies in children with hemianopia.
AB  - Multiple hypometric (undershooting) saccades are generally reported as a
      compensatory strategy in adults with homonymous hemianopia. However, hypermetric
      (overshooting) saccades have been reported to develop spontaneously as a
      beneficial strategy in response to predictable targets. We examined the saccades
      of 10 children (aged 5 to 16 years) with homonymous hemianopia to determine the
      type of compensatory eye-movement strategies employed 6 months to 16 years after
      hemianopia onset. Homonymous hemianopia was identified using perimetry and/or
      pattern visual evoked potentials and supported with results of neuroimaging. Eye
      movements were recorded using bitemporal electrooculography. Saccades were
      elicited to a red light source in a semipredictable paradigm. We found that
      hypermetria was not a consistent compensatory strategy in our patients. In spite
      of the predictability of our paradigm and the long follow-up period, multiple
      hypometric saccades into the blind field appeared to be the preferred strategy.

PMID- 9766740
TI  - Musculoskeletal modelling in determining the effect of botulinum toxin on the
      hamstrings of patients with crouch gait.
AB  - This study aimed to determine the effect of hamstring botulinum toxin A (Btx-A)
      injection in 10 children with crouch gait in terms of changes in muscle length
      and lower-limb kinematics. Before Btx-A injection limb kinematics were recorded.
      Maximum hamstring lengths and excursions were calculated by computer modelling of
      the lower limb. Data were compared with the averaged hamstring lengths of 10
      control children. Hamstrings were defined as short if their length was shorter
      than the average maximum length minus one standard deviation. Gait analysis was
      repeated 2 weeks after isolated hamstring Btx-A injection. Pre- and postinjection
      kinematic data and muscle lengths were then compared. Four of 18 injected limbs
      in three subjects had short medial hamstring before injection, none of the
      subjects had short lateral hamstrings. Muscle excursion was significantly reduced
      in the short and adequate maximum muscle length groups. A significant increase in
      the semimembranosus and semitendinosus length in all of the injected limbs was
      noted. Only in the short muscle group was a significant increase in muscle
      excursion observed. Knee extension improved by 13 degrees in the adequate muscle
      length group and by 15.6 degrees in the short muscle length group. Pelvic tilt
      and hip flexion increased in both groups non-significantly. Average walking speed
      postinjection increased from 0.60 ms(-1) to 0.71 ms(-1). Short hamstrings are
      over-diagnosed in crouch gait. Hamstring Btx-A injection in patients with crouch
      gait produces significant, repeatable muscle lengthening and improved ambulatory
      function.

PMID- 9766742
TI  - Acute transverse myelitis in childhood: nine cases and review of the literature.
AB  - Acute transverse myelitis (ATM) is a rare disease in childhood and adolescence.
      It is characterized by paraplegia with or without sensory symptoms and bladder
      dysfunction, and typically manifests itself over a period of hours to 1 week.
      This is a report of nine patients who were treated between 1993 and 1996. To
      exclude treatable conditions, spinal and cranial MRI with and without contrast
      medium, electrophysiologic tests, and CSF examinations are performed as soon as
      possible after onset. At present post- or parainfectious inflammation is thought
      to be the most frequent cause of ATM. Some causes of ATM can be proved only by
      follow-up examination. The most important differential diagnoses are multiple
      sclerosis and Guillain-Barre syndrome with its variants. After exclusion of
      spinal cord compression, and if specific antibiotic treatment is not possible, a
      3-day high-dose i.v. steroid pulse therapy is the most promising treatment.
      Prognosis is variable and residual symptoms are common. A controlled multicenter
      study is suggested to assess epidemiology, etiology, and prognosis of ATM.

PMID- 9766743
TI  - Movement disorders in association with herpes simplex virus encephalitis in
      children: a review.

PMID- 9766744
TI  - Under-reporting of clinical trials is a well known 'occupational hazard'.

PMID- 9766745
TI  - Problems in the classification of CMML--dysplastic versus proliferative type.
AB  - The FAB group proposed to distinguish two subgroups of chronic myelomonocytic
      leukemia (CMML). Depending on the total leukocyte count, a myelodysplastic type
      (MDS-CMML) (< or = 13,000 microl(-1)) was separated from a myeloproliferative
      type (MPD-CMML) (> 13,000 microl(-1)). Based on retrospective analyses of 158
      patients with CMML, we compared the presenting clinical and hematological
      features of both disorders and examined whether the refined classification is
      important in terms of prognosis. There were 81 patients with MDS-CMML and 77
      patients with MPD-CMML. Median age of patients at diagnosis (70 versus 72 years)
      was not different. The sex ratio showed a preponderance of males in the MPD group
      (m:f; 2.1:1). Splenomegaly was more common in MPD-CMML (54 versus 30%; P =
      0.002). With regard to laboratory findings, patients with MPD-CMML presented with
      significantly higher LDH values (medians 295 versus 231 U ml(-1); P = 0.008) and
      higher serum deoxythymidine kinase levels (medians 150 versus 41 U microl(-1); P
      = 0.0025). Except for white blood cell count (WBC), peripheral blood counts were
      not different. Median percentage of bone marrow blasts was 9% and cumulative
      survival rates were similar in both disorders. Two years after diagnosis,
      actuarial survival for patients with MPD-CMML was 33%, as compared to 50% for
      patients with MDS-CMML (P = 0.31). The probability of transformation to AML was
      higher in MDS-CMML (32 versus 17% after 5 years), but this difference also did
      not reach statistical significance. The survival of patients with MDS-CMML was
      similar to that of other MDS patients (RAEB) who had corresponding medullary
      blast counts. Using the Dusseldorf-score, we could define two risk groups within
      MDS-CMML with a median survial of 12 versus 40 months (P = 0.001). None of the
      known scoring systems could define risk groups within the MPD-CMML group. In
      summary, these data suggest that MDS-CMML and MPD-CMML are clinically
      distinguishing conditions, but the separation provides little prognostic
      information. Further studies are needed to clarify whether response to therapy is
      different in MDS-CMML and MPD-CMML.

PMID- 9766746
TI  - The classification of chronic myelomonocytic leukaemia.

PMID- 9766747
TI  - Interferon-alpha for the treatment of elderly patients with chronic myeloid
      leukaemia.
AB  - The present retrospective analysis is based on data of 213 patients with chronic
      myeloid leukaemia (CML). They were treated with interferon (IFN)alpha-2C
      (Berofor) at daily doses of 3.5 MU subcutaneously (s.c.), alone or in combination
      with low-dose ara-C or hydroxyurea, according to four consecutive studies of the
      Austrian CML Study Group. Comparisons were made between 41 patients aged > or =
      60 years and 172 younger patients. The elderly patients (median: 64 years; range:
      60-73) showed similar pretreatment characteristics compared with the younger
      group, but included a higher percentage of Sokal Stage three (51 vs 20%). Median
      observation periods were similar (38 vs 39 months), whereas the duration of
      IFNalpha treatment was shorter in the elderly group (median 57 vs 42 weeks). The
      rate of overall haematological responses (73 vs 78%) and complete haematological
      response (44 vs 54%), was similar in both cohorts. Differences seen in partial (5
      vs 12%) and complete cytogenetic response (10 vs 13%), were not statistically
      significant, but a tendency in favour of the younger cohort had to be noted.
      Summing up, in elderly patients acceptable rates of haematological and cytogentic
      response can be expected after treatment with IFNalpha alone or in combination
      with LD ara-C or HU.

PMID- 9766748
TI  - Cytogenetic clonality analysis in monosomy 7 associated with juvenile
      myelomonocytic leukemia: clonality in B and NK cells, but not in T cells.
AB  - It remains unclear which lymphoid lineages are involved in juvenile
      myelomonocytic leukemia (JMML). We report a JMML patient who acquired monosomy 7
      after intensive chemotherapy. In this case, the expression of monosomy 7 was
      analyzed in T, B and natural killer (NK) cells highly purified from peripheral
      blood mononuclear cells of the patient. The fluorescence in situ hybridization
      method revealed the expression of monosomy 7 in B cells, but not T cells. Half of
      the NK cells expressed monosomy 7; when NK cells were divided into CD2- and CD2+
      populations, this abnormality was positive in 91.1% of CD2- NK cells but in only
      14.7% of CD2+ NK cells. These results suggest that, in this JMML patient who
      acquired monosomy 7 after intensive chemotherapy, B cells and half of NK cells,
      but not T cells, have monosomy 7.

PMID- 9766749
TI  - Hemophagocytic syndrome associated with hematological neoplasias.
AB  - Hemophagocytic syndrome (HPS) is a reactive process that complicates several
      diseases including hematological neoplasias (HN). It has been suggested that HPS
      may be a negative prognosis factor for neoplastic diseases. In this retrospective
      analysis, 13 cases with HPS associated to HN were compared with two age, sex,
      diagnosis, disease stage and treatment matched controls in order to determine the
      impact of this syndrome on the survival. Cases with HPS were adult patients with
      a male:female ratio of 1:1 and their clinical picture was characterized by fever,
      lymphadenopathy, hepatosplenomegaly, and pancytopenia. Median survival since HN
      diagnosis was 7 and 48 months for the HPS and control groups, respectively (P =
      0.0001). In ten patients who died, median survival after HPS presentation was 1
      month. These results suggest that the presence of HPS is a negative prognosis
      factor in patients with HN. Due to its high mortality rate, an individualized,
      early, and intensive chemotherapeutic regimen may be required for HN complicated
      with this syndrome.

PMID- 9766750
TI  - c-myc locus amplification and the acquisition of trisomy 8 in the evolution of
      chronic myeloid leukaemia.
AB  - The biological progression of chronic myeloid leukaemia is often associated with
      secondary cytogenetic abnormalities but the molecular mechanisms underlying this
      progression are poorly understood. This study explores the association of c-myc
      gene amplification with the progression of chronic myeloid leukaemia in fourteen
      individuals. Three of these cases showed amplification of c-myc during the course
      of their disease. Cytogenetic and molecular analysis of serial samples from some
      patients suggested the successive expansion of distinct clones of malignant
      cells. Our findings also suggest that trisomy 8 and locus amplification could
      represent alternative mechanisms for increasing c-myc gene dosage.

PMID- 9766751
TI  - Introduction of a normal retinoblastoma (Rb) gene into Rb-deficient
      lymphoblastoid cells delays tumorigenicity in immunodefective mice.
AB  - Inactivation of the Rb susceptibility gene occurs in various human cancers and
      has been associated with tumorigenicity. Rb gene is inactivated in 30% of acute
      leukaemias. The effect of Rb protein expression was assessed in the
      lymphoblastoid cell line IM-9 defective for Rb protein, after stable transfection
      with a wild-type Rb gene. The Rb transgene was under the control of the MoMuLv
      LTR. Protein expression by the transduced cells was confirmed by Western blot and
      flow cytometry analyses. Compared to the parental cell line, growth rate remained
      unchanged in the Rb transfected clones. In SCID mice however, tumor formation
      originating from these clones was delayed. The current data suggest therefore
      that, in this Rb-defective haematopoietic cell line, Rb expression correlates
      with reduced tumorigenicity but not with reduced growth rate.

PMID- 9766752
TI  - Drug-activated multiple pathways of defensin mRNA regulation in HL-60 cells are
      defined by reversed roles of participating protein kinases.
AB  - Defensin transcription in HL-60 promyelocytic leukemia cells is greatly enhanced
      during retinoic acid (RA)-induced differentiation. We have probed this regulatory
      pathway by selective modulation of various kinase activities. Induction was
      potentiated by elevated cAMP and attenuated by protein kinase C inhibition,
      entirely correlated to enhanced or blocked morphological differentiation,
      respectively. Yet, defensin mRNA was also induced in undifferentiated HL-60
      cells, but not in others, by cAMP alone. By contrast, modulators that cooperated
      with RA had adverse effects on the normal capacity of dimethyl sulfoxide to up
      regulate these transcripts as well. Thus, defensin mRNA accumulation can be
      selectively uncoupled from maturation stage; and transcript levels may be
      regulated by multiple pathways, each independently acted upon by different
      chemical inducers.

PMID- 9766753
TI  - Growth-inhibitory effects of transforming growth factor-beta 1 on myeloid
      leukemia cell lines.
AB  - Transforming growth factor-beta1 is a pleiotropic cytokine involved in a variety
      of biological processes in both transformed and normal cells, including
      regulation of cellular proliferation and differentiation; its predominant action
      on hematopoietic cells is to inhibit cell growth. We used growth factor-dependent
      cell lines to assess TGF-beta1 effects on human myeloid leukemia cell growth.
      While four lines were completely or predominantly resistant, TGF-beta1 inhibited
      effectively, albeit to various extents, the growth of 12 other cell lines. This
      effect was dose dependent and specific, because a neutralizing anti-TGF-beta1
      antibody prevented TGF-beta1-induced growth suppression. In the present system,
      basic fibroblast growth factor, known as an antagonist of TGF-beta1 counteracting
      its inhibitory effects, did not abrogate the suppressive effects of TGF-beta1.
      Other growth-stimulatory cytokines negated the TGF-beta1-induced inhibition in
      several cell lines, again to various extents. When proliferation was enhanced by
      growth-promoting cytokines (e.g. granulocyte-macrophage colony-stimulating
      factor, GM-CSF, stem cell factor, SCF, or PIXY-321), some previously TGF-beta1
      sensitive cell lines acquired cellular resistance toward TGF-beta1-mediated
      growth suppression, whereas four other cell lines remained susceptible to TGF
      beta1 growth inhibition despite possible counteraction by other cytokines. Thus,
      three growth response patterns to TGF-beta1 were seen: (1) constitutive
      resistance; (2) factor-dependent relative resistance; and (3) sensitivity to
      growth inhibition indifferent to counteracting cytokines. In the latter case, TGF
      beta1 did not downregulate expression of one specific growth factor receptor.
      These studies indicate that human myeloid leukemia cells, represented here by
      leukemia cell lines as model systems, exhibit heterogeneous growth responses to
      TGF-beta1; its inhibitory effects can be modulated or completely alleviated by
      positive antagonistic cytokines. The availability of TGF-beta1-susceptible and 
      refractory cell lines allows for detailed investigations on the mechanisms of
      these regulatory pathways, the nature of TGF-beta1-resistance, and the possible
      contribution of acquired TGF-beta1-resistance to disease progression.

PMID- 9766754
TI  - Divergent effect of taxol on proliferation, apoptosis and nitric oxide production
      in MHH225 CD34 positive and U937 CD34 negative human leukaemia cells.
AB  - Paclitaxel (Taxol) has been shown to be clinically effective in treatment of
      patients with breast and ovarian cancer. It has also shown promising results in
      various other solid tumours. Paclitaxel has induced apoptosis in the G2/M phase
      of the cell cycle in both HL-60 and U937 human leukaemia cells. A recent study
      has shown a dose-dependent cytotoxicity for both taxanes: paclitaxel (taxol) and
      docetaxel (Taxotere) on fresh leukaemia cells in primary culture from 16 ALL and
      four AML patients and proposed their use in treatment of acute leukaemia
      patients. AML is a heterogeneous disease in which malignant transformation and
      disease progression occur at the level of CD34 positive cells. Also, the multi
      drug resistance gene product, P-glycoprotein is expressed only in CD34 positive
      AML cells. Therefore, an in vitro evaluation of the efficacy of paclitaxel, a P
      glycoprotein substrate, in CD34 positive AML cells is warranted before
      considering its clinical use in acute leukaemia patients. Since all in vitro
      studies of paclitaxel reported so far have involved only CD34 negative (HL-60,
      U937, K562) human AML cells, the aim of the present study was to evaluate
      paclitaxel efficacy against CD34 positive AML cells. The IC50 of paclitaxel for
      apoptosis was significantly higher in MHH225 CD34 positive cells (12 +/- 2
      microM) than in U937 CD34 negative cells (1.7 +/- 0.2 microM), P < 0.001.
      Paclitaxel has a significantly weaker cytotoxic effect on CD34 positive AML
      cells. One log higher concentration of paclitaxel was required in MHH225 CD34
      positive AML cells to achieve the same apoptosis level achieved in U937 CD34
      negative leukaemia cells. Also, at the high concentration achievable in vivo: 10
      microM paclitaxel, only half the MHH225 CD34 positive AML cells were apoptotic
      versus 72% of U937 CD34 negative leukaemia cells. Clearly, paclitaxel has only
      weak or modest in vitro efficacy compared with several conventional anti
      leukaemia drugs used in AML treatment. The present results support the poor level
      of in vivo induction of apoptosis achieved during a phase I clinical study with
      paclitaxel therapy in 26 leukaemia patients. Also, the present results have shown
      a significant increase in nitric oxide production during paclitaxel-induced
      apoptosis in U937 monocytic leukaemia cells, confirming the vital role of nitric
      oxide in mediating paclitaxel-induced apoptosis by monocytic cells. In
      conclusion, the present study has demonstrated a clear difference between the
      effect of paclitaxel on CD34 negative and CD34 positive AML cells. Given its poor
      performance in the phase I clinical study of 26 acute leukaemia patients and the
      present weak in vitro cytotoxic effect, it is unlikely that paclitaxel will have
      a role in the treatment of acute leukaemia. Also, the present study emphasises
      the need to use CD34 positive AML cells such as MHH225 rather than the unsuitable
      lineage-specific CD34 negative cells such as HL-60 or U937 for in vitro pre
      clinical screening of potential novel effective anti-leukaemia agents.

PMID- 9766755
TI  - T lymphocytes from Sezary syndrome patients express beta1 integrins whose beta(1
      6)-branched N-linked oligosaccharides reflect their adhesive capacity.
AB  - Sezary syndrome (Sz), characterized by slowly progressing clonal proliferation of
      CD4+, CD45 RO+ T cells, has several forms that are distinguished according to the
      epidermotropic properties of the pathological cells. In a recent paper (Derappe
      C, Haentjens G, Lemaire S, Feugeas JP, Lebbe C, Pasqualetto V, Bussel A, Aubery
      M, Neel D. Leukemia 1996;10:138), we observed that T lymphocytes from most of the
      Sezary patients [Szbeta(1-6)+] expressed high levels of beta(1-6)-GlcNAc-branched
      N-linked oligosaccharides while T lymphocytes from other patients [Szbeta(1-6)-]
      did not. Because this observation suggests the possibility of two forms of Sz,
      distinguished according to the expression rate of these glycans, we looked for a
      possible relationship between this expression rate and T-cell adhesiveness. Using
      an original protocol (Braut-Boucher F, Pichon J, Rat P, Adolphe M, Aubery M, Font
      J. J Immunol Methods 1995;178:41), we observed that T lymphocytes obtained from
      the Szbeta(1-6)+ patients adhered less to normal keratinocyte monolayers than T
      lymphocytes from Szbeta(1-6)- patients and normal donors. As assessed by FACS
      analysis, all the integrin-subunits studied were more expressed on Szbeta(1-6)-,
      especially alpha4, alpha5, beta1 and beta2, than on Szbeta(1-6)+ and normal
      lymphocytes. Although these results suggest that beta1- and beta2-integrin
      expression is involved in the adhesive properties of these T-cells, other
      factors, such as glycosylation, may also contribute. To demonstrate this
      possibility, we sought the presence of beta(1-6)-GlcNAc-branched N-linked
      oligosaccharides on beta1 integrins expressed by T lymphocytes from Sz patients.
      Immunoblot experiments, performed using the specific lectin from Phaseolus
      vulgaris (Leukoagglutinin form), showed that only the beta1 integrin subunit
      expressed by T lymphocytes from Szbeta(1-6)+ patients carried these glycans,
      supporting the concept of the involvement of T-cell glycosylation in the
      evolution of Sz.

PMID- 9766756
TI  - Differential adhesiveness between blood and marrow leukemic cells having similar
      pattern of VLA adhesion molecule expression.
AB  - Functional adhesion of blood and marrow leukemic cells from 14 acute myeloid
      leukemia patients presenting with hyperleukocytosis was evaluated by performing
      cytoadhesion assays on purified (extracellular matrix proteins) and non-purified
      supports (MRC5 fibroblastic cell line). Results, in 30-min chromium release
      assay, show a mean +/- S.D. adhesion to fibronectin, collagen, and laminin
      respectively of 30 +/- 17%, 20 +/- 13%, 25 +/- 17% for blood leukemic cells and
      18 +/- 11%, 11 +/- 10%, 11 +/- 8% for marrow leukemic cells. These differences
      between blood and marrow cells were statistically significant (respectively P =
      0.005, P = 0.01 and P = 0.002), while no difference was noted regarding adhesion
      to non-purified supports. The higher adhesion of blood blast cells to purified
      supports was observed regardless of CD34 expression. No significant difference
      was observed in the expression of cell surface VLA-molecules (CD29, CD49b, CD49d,
      CD49e, CD49f) between blood and marrow blast cells. The addition of GM-CSF or G
      CSF induced increased adhesion of marrow blasts and decreased adhesion of blood
      blasts leading to a loss of the difference between blood and marrow cells. In a
      60-min chromium release assay, marrow blasts adhered even more than blood
      leukemic cells to fibronectin. In contrast, marrow blasts from 'aleukemic' acute
      myeloid leukemia patients did not show any modification regarding their adhesion
      to extracellular matrix proteins when co-cultured with growth factors.

PMID- 9766757
TI  - Trisomy 5 in two cases of acute monocytic leukemia with hyperdiploid clones.
AB  - Although numerical chromosomal aberrations are commonly seen in acute myeloid
      leukemia (AML), trisomy 5 (+ 5) is very rarely detected. We report two patients,
      both of whom suffered from acute monocytic leukemia, in which + 5 was found in
      hyperdiploid clones. A review of the English literature shows 17 additional cases
      of AML with + 5 in at least one of the abnormal clones, making a total of 19 such
      cases including ours. Trisomy 5 has been reported in all FAB subtypes of AML
      except acute promyelocytic leukemia. In the 19 cases identified in this report, +
      5 was found in association with other numerical changes (four cases), structural
      changes (five cases) or both (eight cases). Trisomy 5 as a sole karyotypic
      abnormality was exceedingly rare (two cases). Its biologic and prognostic
      significance remains to be determined.

PMID- 9766758
TI  - Abnormal expression of the Wilms' tumor gene WT1 in juvenile chronic myeloid
      leukemia and infantile monosomy 7 syndrome.

PMID- 9766759
TI  - Orphanages: an idea whose time has come again?

PMID- 9766760
TI  - Age-associated testosterone decline in men: clinical issues for psychiatry.
AB  - OBJECTIVE: The author summarizes current knowledge about the diagnosis and
      treatment of testosterone decline in healthy aging men and the associated
      clinical issues for psychiatry. METHOD: A MEDLINE search was conducted in which
      the search terms "male climacteric," "male menopause," "andropause," "viropause,"
      "low-testosterone syndrome," and "testosterone replacement therapy" were used.
      Literature published before 1966 was identified by reviewing the reference lists
      of later publications. RESULTS: Manifestations of testosterone deficiency have
      included depression, anxiety, irritability, insomnia, weakness, diminished
      libido, impotence, poor memory, reduced muscle and bone mass, and diminished
      sexual body hair. Although testosterone levels decline with age, there is great
      interindividual variability, and the connection between serum testosterone levels
      and clinical psychiatric signs and symptoms is not clear-cut, since other
      hormonal changes are implicated as well. Testosterone replacement therapy may
      offer hypogonadal men benefit, but long-term studies on its efficacy and safety
      are lacking. Comprehensive biopsychosocial assessment should be a routine part of
      the evaluation of complaints of low-testosterone syndrome in men. CONCLUSIONS:
      Testosterone decline/deficiency is not a state strictly analogous to female
      menopause and may exhibit considerable overlap with primary and other secondary
      psychiatric disorders.

PMID- 9766761
TI  - The orphans of Eritrea: are orphanages part of the problem or part of the
      solution?
AB  - OBJECTIVE: This study compared the mental health and cognitive development of 9-
      to 12-year-old Eritrean war orphans living in two orphanages that differed
      qualitatively in patterns of staff interaction and styles of child care
      management. METHOD: The directors and several child care workers at each
      institution were asked to complete staff organization and child management
      questionnaires. The psychological state of 40 orphans at each institution was
      evaluated by comparing their behavioral symptoms and performance on cognitive
      measures. RESULTS: Orphans who lived in a setting where the entire staff
      participated in decisions affecting the children, and where the children were
      encouraged to become self-reliant through personal interactions with staff
      members, showed significantly fewer behavioral symptoms of emotional distress
      than orphans who lived in a setting where the director made decisions, daily
      routines were determined by explicit rules and schedules, and interactions
      between staff members and the children were impersonal. CONCLUSIONS: When
      orphanages are the only means of survival for war orphans, a group setting where
      the staff shares in the responsibilities of child management, is sensitive to the
      individuality of the children, and establishes stable personal ties with the
      children serves the emotional needs and psychological development of the orphans
      more effectively than a group setting that attempts to create a secure
      environment through an authoritative style of management with explicit rules and
      well-defined schedules.

PMID- 9766762
TI  - Dopamine transporter occupancies in the human brain induced by therapeutic doses
      of oral methylphenidate.
AB  - OBJECTIVE: The therapeutic effects of methylphenidate in the treatment of
      attention deficit disorder have been attributed to its ability to increase the
      synaptic concentration of dopamine by blocking the dopamine transporters.
      However, the levels of dopamine transporter blockade achieved by therapeutic
      doses of methylphenidate are not known. This study measured, for the first time,
      dopamine transporter occupancy by orally administered methylphenidate in the
      human brain and its rate of uptake in the brain. METHOD: Positron emission
      tomography (PET) and [11C]cocaine were used to estimate dopamine transporter
      occupancies after different doses of oral methylphenidate in seven normal
      subjects (mean age=24 years, SD=7). In addition, the pharmacokinetics of oral
      methylphenidate were measured in the baboon brain through use of PET and
      [11C]methylphenidate administered through an orogastric tube. RESULTS: At 120
      minutes after administration, oral methylphenidate produced a dose-dependent
      blockade of dopamine transporter; means=12% (SD= 4%) for 5 mg, 40% (SD=12%) for
      10 mg, 54% (SD=5%) for 20 mg, 72% (SD=3%) for 40 mg, and 74% (SD=2%) for 60 mg.
      The estimated dose of oral methylphenidate required to block 50% of the dopamine
      transporter corresponded to 0.25 mg/kg. Oral methylphenidate did not reach peak
      concentration in brain until 60 minutes after its administration. CONCLUSIONS:
      Oral methylphenidate is very effective in blocking dopamine transporters, and at
      the weight-adjusted doses used therapeutically (0.3 to 0.6 mg/kg), it is likely
      to occupy more than 50% of the dopamine transporters. The time to reach peak
      brain uptake for oral methylphenidate in brain corresponds well with the reported
      time course to reach peak behavioral effects.

PMID- 9766763
TI  - Serotonin transporter protein gene polymorphism and personality measures in
      African American and European American subjects.
AB  - OBJECTIVE: The SLC6A4 locus encodes the serotonin transporter, which in turn
      mediates the synaptic inactivation of the neurotransmitter serotonin. A
      polymorphism located in the 5' promoter region of the gene is associated with
      altered transcriptional activity of SLC6A4; an earlier study reported an
      association of the polymorphism with anxiety- and depression-related traits,
      including harm avoidance and neuroticism. The authors attempted to replicate this
      finding. METHOD: They assessed genotype at the SLC6A4 promoter polymorphism, and
      an additional polymorphism in intron 2, in 322 American subjects of European and
      African ancestry, some with diagnoses of a personality disorder or substance
      dependence and some normal comparison subjects. Harm avoidance was measured by
      the Tridimensional Personality Questionnaire in all subjects, and neuroticism was
      measured by the NEO Five-Factor Inventory in 185 subjects. Allele frequencies in
      the groups were compared, and hierarchical multiple regression was used to
      examine the correlation of demographic features, psychiatric diagnostic group,
      and genotype with harm avoidance and neuroticism scores. RESULTS: Although the
      demographic factors and psychiatric diagnoses had effects on harm avoidance and
      neuroticism scores, there was no main effect of genotype on these personality
      measures. In the context of these overall negative findings, interactions were
      observed between sex and promoter system genotype and between race and promoter
      system genotype which suggest that the present findings are not wholly
      inconsistent with those of the earlier study. CONCLUSIONS: The authors were
      unable to replicate the association finding. The specific phenotypic composition
      of the groups studied with respect to other behaviors could have influenced
      ability to detect association of SLC6A4 polymorphisms with personality measures;
      population stratification for this locus is also of potential importance.

PMID- 9766764
TI  - Short-term augmentation of fluoxetine with clonazepam in the treatment of
      depression: a double-blind study.
AB  - OBJECTIVE: Because selective serotonin reuptake inhibitors (SSRIs) require 2-4
      weeks to reach efficacy, the authors determined whether clonazepam augmentation
      of fluoxetine is superior to fluoxetine alone at the beginning of treatment for
      major depression. METHOD: Eighty adult outpatients with major depression who were
      rated as "moderately ill" or "markedly ill" on the Clinical Global Impression of
      Severity underwent 8 weeks of double-blind, randomized treatment with fluoxetine,
      20 mg/day for all patients initially and 40 mg/day if needed after 6 weeks. One
      half of these patients received clonazepam, 0.5 mg h.s. adjusted to two tablets
      by day 10 if needed, and the remainder received placebo, likewise adjusted.
      Clonazepam/placebo was gradually discontinued during days 21-33. Efficacy was
      evaluated by means of the Hamilton Depression Rating Scale, the Clinical Global
      Impression of Improvement, and a patient rating of global improvement. RESULTS:
      The patients taking clonazepam improved significantly more during the first 3
      weeks of treatment according to ratings on the Hamilton scale (> or =50%
      improvement) and the clinician- and patient-rated global improvement measures
      ("much" or "very much" improved). Analysis of variance confirmed a significant
      effect of clonazepam for average Hamilton depression scores. No serious adverse
      events were found in either treatment group. Taper effects appeared modest and
      transitory. CONCLUSIONS: Clonazepam augmentation of fluoxetine was superior to
      fluoxetine alone in the first 3 weeks of treatment. This strategy may reduce
      suffering during early SSRI treatment, may partially suppress SSRI side effects,
      may increase compliance, and could possibly reduce the risk of suicide.

PMID- 9766765
TI  - Effect of pindolol on onset of action of paroxetine in the treatment of major
      depression: intermediate analysis of a double-blind, placebo-controlled trial.
      Reseau de Recherche et d'Experimentation Psychopharmacologique.
AB  - OBJECTIVE: The purpose of this study was to investigate the effect of pindolol to
      accelerate the onset of action of paroxetine in patients suffering from major
      depression. METHOD: Patients who met DSM-IV criteria for a nonpsychotic disorder,
      who had no previously treated episode of major depression episode, and who had a
      score of at least 18 on the 17-item Hamilton Depression Rating Scale were
      randomly assigned, for the first 21 days, to treatment with paroxetine (20
      mg/day) and either pindolol (5 mg t.i.d.) or placebo. Patients were evaluated
      with the Hamilton depression scale, the Montgomery-Asberg Depression Rating
      Scale, and Global Clinical Impression (CGI) on days 0 (baseline), 5, 10, 15, 21,
      25, 31, 60, 120, and 180. RESULTS: Intermediate analysis of the first month's
      results for the first 100 patients (pindolol, N=50; placebo, N=50) was performed.
      At day 10 there were more improved patients (defined as patients with a maximum
      score of 10 on the Hamilton depression scale) in the pindolol plus paroxetine
      group (N=24; 48%) than in the placebo plus paroxetine group (N=13; 26%). At day 5
      there was no statistically significant difference, and at day 15 and thereafter,
      the differences between the two groups disappeared. Hamilton depression scale
      scores were significantly lower on days 5 and 10 for the pindolol plus paroxetine
      group (mean=15.7, SD=5.3, and mean=11.7, SD=6.4, respectively) than for the
      placebo plus paroxetine group (mean=19, SD=5.9, and mean=14.7, SD=6.8); this was
      also true for Montgomery-Asberg depression scale and CGI scores. CONCLUSIONS: The
      addition of pindolol to paroxetine treatment significantly accelerates the onset
      of therapeutic response in patients suffering from major depression.
      Nevertheless, the mechanism (pharmacodynamic or pharmacokinetic) of this
      beneficial effect remains unclear.

PMID- 9766766
TI  - Association between eye tracking disorder in schizophrenia and poor sensory
      integration.
AB  - OBJECTIVE: The authors tested the hypothesis that eye tracking disorder in
      schizophrenia is associated with neurological signs. METHOD: The subjects were 93
      normal comparison subjects and 59 schizophrenic patients. They were evaluated
      with the Neurological Evaluation Scale, a standardized rating instrument that
      assesses sensory integration, motor coordination, sequencing of complex motor
      acts, and other neurological signs. Also, the schizophrenic patients' smooth
      pursuit eye movements were tested in response to a 0.3-Hz sinusoidal target by
      means of infrared oculography. They were divided into those with (N=18) and
      without (N=41) eye tracking disorder by using a previously described method,
      which was based on mixture analysis of the distribution of position root mean
      square error. RESULTS: The patients with eye tracking disorder had significantly
      worse performance than the patients without eye tracking disorder with respect to
      sensory integration, and the effect size was moderate to large. In comparison
      with the normal subjects, both patient subgroups had significantly worse
      performance on all of the Neurological Evaluation Scale subscales. CONCLUSIONS:
      Although neurological signs are present generally in schizophrenia, poor sensory
      integration is particularly pronounced in patients with eye tracking disorder. A
      review of the literature shows that the two abnormalities have strikingly similar
      patterns of validators, including 1) familial aggregation, 2) premorbid presence,
      3) syndromal specificity, 4) trait status, and 5) association with the deficit
      syndrome. Poor sensory integration and eye tracking disorder in schizophrenia may
      be various manifestations of a common, underlying pathophysiological process.

PMID- 9766767
TI  - Are there sex differences in neuropsychological functions among patients with
      schizophrenia?
AB  - OBJECTIVE: Studies of sex differences in neuropsychological performance in
      schizophrenia report inconsistent results, due in part to methodological
      artifacts. The study presented here was specifically designed to examine sex
      differences in neuropsychological performance. It was hypothesized that
      schizophrenic women would exhibit fewer neuropsychological deficits than
      schizophrenic men and that their performance would be more similar to that of
      normal women than schizophrenic men's performance would be to that of normal men.
      METHOD: Thirty-one outpatients with DSM-III-R-defined schizophrenia were
      systematically sampled from an extensive service network serving a large urban
      catchment area for seriously mentally ill persons. Twenty-seven normal comparison
      subjects were matched within sex on the basis of age, parental socioeconomic
      status, ethnicity, and handedness. An extensive neuropsychological test battery
      was administered, and multivariate analysis of variance was used to test for the
      effects of sex and group and sex-by-group interactions. RESULTS: Male patients
      were significantly impaired across all functions in comparison with normal male
      subjects and on tests of attention, verbal memory, and executive functions in
      comparison with female patients. Female patients performed significantly worse
      than female normal comparison subjects only on tests of attention, executive
      functions, visual memory, and motor functions. CONCLUSIONS: The findings suggest
      that women with schizophrenia may be less vulnerable to particular cognitive
      deficits, especially those involving verbal processing, than schizophrenic men.

PMID- 9766768
TI  - Concordance for sex and the pseudoautosomal gene hypothesis revisited: no
      evidence of increased sex concordance in a nationwide Finnish sample of siblings
      with paternally derived schizophrenia.
AB  - OBJECTIVE: This study set out to determine, in a homogeneous sample with
      nationwide coverage in Finland, whether siblings treated for schizophrenia are
      more often of the same sex than expected by chance, and whether this is
      especially so when the disorder is transmitted by their fathers. METHOD: Finnish
      social and health insurance files as well as hospital discharge registers were
      searched for probands with schizophrenia from a birth cohort spanning 30 years.
      Nuclear families were identified by cross-linkage with the national birth
      register, and the sex distribution observed in multiply affected sibships was
      compared with expected distributions by maximum likelihood analysis. RESULTS: In
      the subset of multiply affected sibships with one parent who had schizophrenia
      (84 fathers and 120 mothers), the observed sex distribution did not deviate from
      the expected pattern. However, a small and marginally significant excess of sex
      concordance emerged from the total sample of 1,942 sibships in which there were
      at least two affected members, irrespective of the parents' affection status.
      CONCLUSIONS: The results indicate that no above-chance sex concordance in
      sibships multiply affected with paternally transmitted schizophrenia is present
      in the genetically homogeneous population of Finland. In view of a virtually
      unbiased and complete ascertainment procedure and sample sizes one to two orders
      of magnitude larger than those in previous studies, the authors attribute prior
      findings of such a concordance to sampling artifacts or chance fluctuations and
      finally conclude that except for regional genetic isolates, there is no
      epidemiologic evidence that a gene accounting for substantial susceptibility to
      schizophrenia in a greater proportion of cases resides in the pseudoautosomal
      region of the sex chromosomes.

PMID- 9766769
TI  - Common pattern of cortical pathology in childhood-onset and adult-onset
      schizophrenia as identified by proton magnetic resonance spectroscopic imaging.
AB  - OBJECTIVE: Multislice proton magnetic resonance spectroscopic imaging (1H-MRSI)
      permits simultaneous acquisition and mapping of signal intensities of N-acetyl
      containing compounds (mainly N-acetylaspartate, NAA), choline-containing
      compounds (CHO), and creatine plus phosphocreatine (CRE) from multiple whole
      brain slices consisting of small single-volume elements. Previous 1H-MRSI studies
      of adult patients with schizophrenia showed small NAA relative signals in the
      hippocampal area and in the dorsolateral prefrontal cortex in comparison with
      healthy subjects. As part of a program to address the pathophysiological
      continuity between childhood-onset and adult-onset schizophrenia, the authors
      performed 1H-MRSI of patients with childhood-onset schizophrenia to specifically
      test whether the hippocampal area and dorsolateral prefrontal cortex show the
      same abnormalities as seen in adult-onset schizophrenia. METHOD: A 1.5-T nuclear
      magnetic resonance machine was used to test 14 patients (mean age, 16.4 years)
      and 14 comparison subjects. Ratios of areas under the metabolite peaks of the
      proton spectra were determined (i.e., NAA/CRE, NAA/CHO, CHO/CRE) for multiple
      cortical and subcortical regions. RESULTS: The patients showed significantly
      lower NAA/CRE ratios bilaterally in the hippocampal area and the dorsolateral
      prefrontal cortex than the comparison subjects. There were no significant
      differences in CHO/CRE or in NAA ratios in any other area sampled. CONCLUSIONS:
      The present study shows that patients with childhood-onset schizophrenia have
      smaller than normal regional NAA relative signals, suggesting neuronal damage or
      malfunction in the hippocampal area and dorsolateral prefrontal cortex. These
      differences were similar in magnitude to those found in patients with adult-onset
      schizophrenia. The present data extend other evidence of a biological continuum
      between childhood- and adult-onset schizophrenia.

PMID- 9766770
TI  - Lower left temporal lobe MRI volumes in patients with first-episode schizophrenia
      compared with psychotic patients with first-episode affective disorder and normal
      subjects.
AB  - OBJECTIVE: Magnetic resonance imaging (MRI) studies of schizophrenic patients
      have revealed structural brain abnormalities, with low volumes of gray matter in
      the left posterior superior temporal gyrus and in medial temporal lobe
      structures. However, the specificity to schizophrenia and the roles of chronic
      morbidity and neuroleptic treatment in these abnormalities remain unclear.
      METHOD: Magnetic resonance (1.5-T) scans were obtained from 33 patients with
      first-episode psychosis and 18 age-matched normal comparison subjects, all right
      handed. Sixteen of the patients were diagnosed with affective disorder and 17
      with schizophrenia. RESULTS: Quantitative volumetric analysis showed that the
      patients with first-episode schizophrenia had significantly smaller gray matter
      volume in the left posterior superior temporal gyrus than did the patients with
      first-episode affective psychosis or the comparison subjects, with a significant
      left-less-than-right asymmetry. The schizophrenic patients also showed a smaller
      gray matter volume of the left posterior amygdala-hippocampal complex than the
      comparison subjects. Both the patients with schizophrenia and those with
      affective psychosis had significant left-less-than-right asymmetry of the
      posterior amygdala-hippocampal complex. CONCLUSIONS: These findings suggest that
      temporal lobe abnormalities are present at the first hospitalization for
      schizophrenia and that low volume of the left posterior superior temporal gyrus
      gray matter is specific to schizophrenia compared with affective disorder.

PMID- 9766772
TI  - Latent class analysis of lifetime depressive symptoms in the national comorbidity
      survey.
AB  - OBJECTIVE: Although clinical trials have documented the importance of identifying
      individuals with major depression with atypical features, there are fewer
      epidemiological data. In a prior report, the authors used latent class analysis
      (LCA) to identify a distinctive atypical depressive subtype; they sought to
      replicate that finding in the current study. METHOD: Using the National
      Comorbidity Survey data, the authors applied LCA to 14 DSM-III-R major depressive
      symptoms in the participants' lifetime worst episodes (N=2,836). Validators of
      class membership included depressive disorder characteristics, syndrome
      consequences, demography, comorbidity, personality/attitudes, and parental
      psychiatric history. RESULTS: The best-fitting LCA solution had six classes. Four
      were combinations of atypicality and severity: severe atypical, mild atypical,
      severe typical, and mild typical. Syndrome severity (severe atypical and typical
      versus mild atypical and typical classes) was associated with a pronounced
      pattern of more and longer episodes, worse syndrome consequences, increased
      psychiatric comorbidity, more deviant personality and attitudes, and parental
      alcohol/drug use disorder. Syndrome atypicality (severe and mild atypical versus
      severe and mild typical classes) was associated with decreased syndrome
      consequences, comorbid conduct disorder and social phobia, higher interpersonal
      dependency and lower self-esteem, and parental alcohol/drug use disorder.
      CONCLUSIONS: As in prior reports, the atypical subtype of depression can be
      identified in epidemiological samples and, like typical depression, exists in
      mild and severe variants. Atypical depressive subtypes were characterized by
      several distinctive features. However, the correspondence between
      epidemiologically derived typologies of atypical depression and DSM-IV major
      depression with atypical features is not yet known.

PMID- 9766771
TI  - Relationship between type of insurance and care during the early course of
      psychosis.
AB  - OBJECTIVE: Little is known about the relationship between insurance and care in
      the early course of psychosis. This study explored the insurance status of first
      admission psychotic patients and the relationship between type of insurance and
      care received up to this admission. METHOD: Data are from the Suffolk County
      Mental Health Project, an epidemiologic study of first-admission psychosis. Data
      on insurance status (N=525) were pooled from hospital records, respondents, and
      significant others. Logistic regression analysis, controlling for key background
      variables and diagnosis, was used to study the relationship between insurance and
      care. RESULTS: At first admission, 233 (44%) of the patients had no insurance, 78
      (15%) had Medicaid or Medicare, 203 (39%) had private insurance, eight (1.5%)
      were insured by the Veterans Administration, and the insurance status of three
      (1.5%) was unknown. Having private insurance increased the likelihood of having
      received previous mental health treatment (psychotherapy specifically), being
      admitted voluntarily, being hospitalized in a community hospital rather than a
      public hospital, and being hospitalized within 3 months of onset of psychosis.
      Having Medicaid/Medicare increased the likelihood of receiving nonantipsychotic
      medication before this hospitalization, admission to a community hospital rather
      than a public hospital, having received previous mental health treatment in
      general, and voluntary admission. CONCLUSIONS: During the early course of
      psychotic illness, many people lack any type of health insurance, and this is
      associated with a decreased likelihood of obtaining care before their first
      hospital admission.

PMID- 9766773
TI  - Lifetime and twelve-month prevalence rates of major depressive episodes and
      dysthymia among Chinese Americans in Los Angeles.
AB  - OBJECTIVE: The authors' goal was to estimate the lifetime and 12-month rates of
      major depressive episodes and dysthymia for Chinese Americans who reside in Los
      Angeles. This effort, the Chinese American Psychiatric Epidemiological Study, is
      the first large-scale community psychiatric epidemiological study on an Asian
      American ethnic group that used DSM-III-R criteria for major depressive episodes
      and dysthymia. METHOD: A multi-stage sampling design was used to select
      respondents for participation in the survey. The sample included 1,747 adults, 18
      65 years of age, who resided in Los Angeles County and who spoke English,
      Mandarin, or Cantonese. RESULTS: Approximately 6.9% of the respondents had
      experienced an episode of major depression and 5.2% had had dysthymia in their
      lifetime. The 12-month rates of depressive episode and dysthymia were 3.4% and
      0.9%, respectively. The most consistent correlate of lifetime and 12-month
      depressive episode and dysthymia was social stress, measured by past traumatic
      events and recent negative life events. CONCLUSIONS: The Chinese American
      Psychiatric Epidemiological Study provides a rare opportunity to investigate the
      heterogeneity within a single Asian American ethnic group, Chinese Americans, and
      to identify the subgroups among Chinese Americans who may be most at risk for
      mental health problems.

PMID- 9766774
TI  - Psychiatric disorder onset and first treatment contact in the United States and
      Ontario.
AB  - OBJECTIVE: The authors describe the timing of the first treatment contact
      following new-onset DSM-III-R mood, anxiety, and addictive disorders in community
      samples from the United States and Ontario, Canada, before and after passage of
      the Ontario Health Insurance Plan. METHOD: The authors drew data from the
      National Comorbidity Survey (NCS) (N=8,098) and the mental health supplement to
      the Ontario Health Survey (OHS) (N= 9,953). They assessed psychiatric disorders
      with a modified version of the Composite International Diagnostic Interview; they
      also assessed retrospectively age at disorder onset and first treatment contact.
      They used the Kaplan-Meier method to generate time-to-treatment curves and
      survival analysis to compare time-to-treatment intervals across the two surveys.
      RESULTS: The overall time-to-treatment curves revealed substantial differences
      between disorders that were consistent across the two surveys. In both surveys,
      panic disorder had the highest probability of first-year treatment (NCS, 65.6%;
      OHS supplement, 52.6%), while phobia (NCS, 12.0%; OHS supplement: 6.5%) and
      addictive disorders (NCS, 6.4%; OHS supplement, 4.2%) had the lowest in both
      surveys. Retrospective subgroup analysis suggests that before the passage of the
      Ontario public insurance plan, the likelihood of receiving treatment in the year
      of disorder onset was greater in Ontario than in the United States but that this
      relationship reversed following passage of the Ontario plan. During this period,
      the authors observed no significant between-country differences in the
      probability of prompt treatment of adults with 12 or fewer years of education.
      CONCLUSIONS: These results challenge the assumption that the universal health
      insurance plan in Ontario promotes greater access to mental health services than
      is available in the United States for vulnerable groups. Marked differences
      between disorders in the speed to first treatment suggest that in both countries,
      clinical factors play an important role in the timing of the initial decision to
      seek treatment.

PMID- 9766775
TI  - Interrater agreement among psychiatrist in psychiatric emergency assessments.
AB  - OBJECTIVE: The authors' purpose in this study was to investigate the interrater
      agreement among psychiatrists in psychiatric emergency service settings. The
      interrater reliability of many of the key concepts in psychiatric emergency
      service settings has not been studied. METHOD: Videotapes of 30 psychiatric
      emergency service patient assessment interviews conducted by psychiatrists were
      shown to eight experienced psychiatric emergency service psychiatrists. The eight
      psychiatrists rated each videotape on dimensions such as severity of depression
      and psychosis and recommended a disposition for each patient. Interrater
      reliability was then explored. RESULTS: The level of agreement (intraclass
      correlation coefficient) among the reviewing psychiatrists was higher for
      psychosis and substance abuse but lower for psychopathology, impulse control
      problems, danger to self, and disposition. The reviewers' disposition
      recommendations did not match well with the assessing psychiatrist's actual
      disposition, but comparisons with actual practice should be considered only
      suggestive. CONCLUSIONS: Psychiatric emergency service assessments need
      improvement. This may be accomplished by exploring the underlying structure of
      psychiatric emergency service concepts, the creation and validation of structured
      assessment tools, and the creation of practice guidelines.

PMID- 9766776
TI  - Intensive community-focused treatment of veterans with dual diagnoses.

PMID- 9766777
TI  - Rapid cycling in women and men with bipolar manic-depressive disorders.
AB  - OBJECTIVE: This study investigated risks for rapid cycling, as defined by DSM-IV,
      in women and men with bipolar disorders. METHOD: The results of 10 studies with a
      total of 2,057 bipolar patients were meta-analyzed by pooled contingency methods.
      RESULTS: The proportions of women and men among rapid-cycling cases averaged 72%
      and 28%, respectively, but the risk of rapid cycling was inconsistently more
      frequent among women (29.6%) than among men (16.5%). The mean number of episodes
      per year was much higher in rapid-cycling patients before and during lithium
      treatment but was similar in rapid-cycling men and women. CONCLUSIONS: Rapid
      cycling was only moderately, and inconsistently, more common in bipolar women
      than men.

PMID- 9766778
TI  - Sex differences in neuropsychological functioning of first-episode and
      chronically ill schizophrenic patients.
AB  - OBJECTIVE: The purpose of this study was to determine whether men and women with
      schizophrenia demonstrate differences in cognitive abilities. METHOD: Two cohorts
      of patients with schizophrenia, an acute first-episode and a chronically
      hospitalized group, were evaluated with a neuropsychological battery and compared
      with a normal group of subjects. RESULTS: After adjustment for age, age at onset,
      and premorbid IQ, male chronic patients performed worse than female chronic
      patients on measures of visual memory. These differences were eliminated after
      control for symptom severity. No other differences were found in cognitive
      function between men and women in either cohort. CONCLUSIONS: Sex differences in
      cognitive function in schizophrenic patients are not robust findings.

PMID- 9766779
TI  - Dopamine D2 receptor density and personal detachment in healthy subjects.
AB  - OBJECTIVE: The purpose of this study was to examine the relationship between the
      personality trait involving personal detachment and dopamine D2 receptor specific
      binding in healthy subjects. METHOD: Eighteen adult subjects completed the
      Karolinska Scales of Personality and the Tridimensional Personality Questionnaire
      and participated in a study that used [11C]raclopride positron emission
      tomography (PET) to quantify striatal D2 receptor binding. RESULTS: A significant
      relationship was found between D2 receptor specific binding and detachment scores
      on the Karolinska Scales of Personality but not between D2 receptor specific
      binding and attachment scores on the Tridimensional Personality Questionnaire. In
      an exploratory analysis, the authors found a significant relationship between
      binding and the sentimentality cluster on the Tridimensional Personality
      Questionnaire but on no other personality clusters scores on the Tridimensional
      Personality Questionnaire or Karolinska Scales of Personality. CONCLUSIONS: These
      findings replicate those of a recent report that personal detachment scores on
      the Karolinska Scales of Personality are related to dopamine D2 receptor density
      and extends this finding by suggesting that the relationship is relatively
      specific to the trait defined by the Karolinska Scales of Personality and does
      not generalize to other forms of detachment.

PMID- 9766780
TI  - Six-year outcome for cognitive behavioral treatment of residual symptoms in major
      depression.
AB  - OBJECTIVE: The authors' goal was to determine whether cognitive behavioral
      treatment of residual symptoms of depression might have a significant effect on
      relapse rate. METHOD: A 6-year follow-up assessment was conducted of 40 patients
      with primary major depressive disorder who had been successfully treated with
      antidepressants and were randomly assigned to either cognitive behavioral
      treatment of residual symptoms or standard clinical management. RESULTS: Ten of
      the patients (50%) in the cognitive behavioral treatment group and 15 (75%) in
      the standard clinical management group relapsed. The difference did not attain
      statistical significance. When multiple relapses were considered, patients in the
      cognitive behavioral treatment group had a significantly lower number of
      depressive episodes than those in the standard clinical management group.
      Patients responded to the same antidepressant drug used in the index episode; in
      two cases (4%), resistance occurred. CONCLUSIONS: The protective effects of
      cognitive behavioral treatment that were evident at 4-year follow-up faded
      afterward. Cognitive behavioral treatment of residual symptoms, however, improved
      the long-term outcome of major depression in terms of total number of episodes
      during the follow-up period.

PMID- 9766781
TI  - Efficient allocation of patients to treatment cells in clinical trials with more
      than two treatment conditions.
AB  - OBJECTIVE: Clinical trials generally allocate patients to equal-sized treatment
      groups. The authors propose that it may be more efficient to allocate unequal
      proportions of the total sample size to treatments when more than two treatments
      are being compared. METHOD: This proposal is illustrated with two examples. One
      involved a comparison of three treatments and used a dichotomous categorical
      outcome. The other involved comparison of three treatments and used a continuous
      measure. RESULTS: In both examples, a considerable increase in efficiency was
      realized by reducing the number of patients assigned to the placebo cell.
      CONCLUSIONS: Unequal allocation of patients to treatments should be considered
      when more than two groups are compared.

PMID- 9766782
TI  - Olanzapine use in women with antipsychotic-induced hyperprolactinemia.

PMID- 9766783
TI  - Extrapyramidal side effects in a patient treated with risperidone plus donepezil.

PMID- 9766784
TI  - Symptom exacerbation of vocal tics and other symptoms associated with
      streptococcal pharyngitis in a patient with obsessive-compulsive disorder and
      tics.

PMID- 9766785
TI  - Clonidine treatment for hallucinogen persisting perception disorder.

PMID- 9766786
TI  - Treatment of Alzheimer's disease.

PMID- 9766787
TI  - Treatment of Alzheimer's disease.

PMID- 9766788
TI  - Cognitive behavior therapy for chronic fatigue syndrome.

PMID- 9766789
TI  - Treatment of dissociative identity disorder.

PMID- 9766790
TI  - Deterioration of olfactory identification abilities in patients with
      schizophrenia.

PMID- 9766791
TI  - Personality disorder diagnoses.

PMID- 9766792
TI  - Sex-related differences in depressed alcoholics.

PMID- 9766793
TI  - Effect of recombinant human erythropoietin treatment on circulating reticulated
      platelets in uremic patients: association with early improvement in platelet
      function.
AB  - Recombinant human erythropoietin improves platelet function in uremia through the
      correction of anemia, but this effect can be seen also before the hematocrit
      rise. We studied 12 hemodialyzed patients (seven men, five women) who received
      recombinant human erythropoietin (40 IU kg(-1)i.v., three times weekly) and were
      evaluated before treatment and after three doses; 24 control subjects were used.
      Platelet aggregation induced by adenosine 5'-diphosphate (ADP), epinephrine,
      collagen, arachidonic acid, and ristocetin, and reticulated platelets determined
      by flow cytometry after staining with thiazole orange were measured. Platelet
      aggregation induced by all the agonists were impaired in uremic patients (P <
      0.01), but ADP and ristocetin-induced aggregations improved after treatment (P <
      0.01). Hemodialyzed patients had less reticulated platelets than controls (P <
      0.01). Reticulated platelets increased after three doses of treatment (P < 0.01).
      In conclusion, improvement of platelet function at early stages of recombinant
      human erythropoietin treatment may be attributed to the increase in young
      platelets detected as reticulated platelets.

PMID- 9766794
TI  - Progressive expansion of hypertensive intracerebral hemorrhage by coagulopathy.
AB  - To test the hypothesis that an impaired coagulation system facilitates rapid
      expansion of hypertensive intracerebral hemorrhage (HICH), coagulation markers
      were assayed in plasma and their relations to both the hemorrhage size and its
      progressive expansion were analyzed. Ninety patients with HICH were studied. On
      admission, plasma samples were taken for the coagulation assay. Hematoma volume
      was calculated from a computed tomography (CT) scan and its enlargement was
      estimated by comparison to the volume of the hematoma calculated from a second CT
      scan taken later within 24 hr. Nine out of 90 patients showed enlargement in
      their hematoma size (enlarged hematoma group). Four of the enlarged hematoma
      group fell into acute fatal deterioration and died. Plasma levels of both fibrino
      peptide A (17.2+/-7.8 vs. 4.0+/-0.6 ng/ml, P < 0.05) and thrombin-antithrombin
      complex (21.9+/-3.1 vs. 7.4+/-2.8 ng/ml, not significant) were higher in the
      unchanged group than those in the enlarged hematoma group. In the hematoma
      enlarged group fibrino-peptide A level did not exceed 10 ng/ml. In the hematoma
      unchanged group thrombin-AT-III complex values were positively correlated to
      hematoma volume. Thus, the coagulation system seemed to be highly activated
      depending on the hemorrhage volume within three hr after ictus in hypertensive
      intracerebral hemorrhage patients. When thrombin generation was not sufficient
      after bleeding, the hematoma seemed to be progressively enlarged. In conclusion,
      plasma levels of the coagulation markers on admission could be useful predictors
      of the possible enlargement of hematoma which leads to a poor outcome.

PMID- 9766795
TI  - Platelet von Willebrand factor in Hermansky-Pudlak syndrome.
AB  - The Hermansky-Pudlak Syndrome (HPS) is an autosomal recessive inherited disorder
      characterized by oculocutaneous albinism, tissue accumulation of ceroid pigment,
      and a mild to moderate bleeding diathesis attributed to storage-pool deficient
      (SPD) platlets. Patients have platelet aggregation and release abnormalities. In
      addition, low levels of plasma von Willebrand factor (vWF) antigen in some HPS
      patients have been associated with a greater bleeding tendency than would be
      predicted from either condition alone. Other HPS patients have severe bleeding
      despite normal levels of plasma vWF, suggesting that at least one additional
      factor is responsible for their bleeding diathesis. Because platelet vWF levels
      have been well correlated with clinical bleeding times in patients with von
      Willebrand's disease, we have measured the platelet vWF activity and antigen
      levels in 30 HPS patients and have attempted to correlate their clinical bleeding
      with these values. The platelet vWF activity levels in patients was significantly
      lower than that of normal subjects (P < 0.0001). The patients as a group also had
      slightly lower values of plasma vWF activity when compared with normals (P-0.03).
      In 11 of the HPS patients, the multimeric structure of plasma vWF showed a
      decrease in the high molecular weight multimers and an increase in the low
      molecular weight multimers. In correlating the platelet and plasma vWF values
      with the bleeding histories, we were not able to show a predictable relationship
      in the majority of the patients.

PMID- 9766796
TI  - Hematological effects of atypical and Cameroon beta-globin gene haplotypes in
      adult sickle cell anemia.
AB  - To examine the effects of unusual or atypical beta-globin gene cluster haplotypes
      on the hematological features and Hb F levels of sickle cell anemia, we studied
      African Americans who had an atypical or Cameroon haplotype chromosome in
      association with a typical haplotype. We identified over 20 atypical haplotypes.
      The distribution of 5' sub-haplotypes of the atypical chromosomes mirrored the
      distribution of common haplotypes in African Americans with sickle cell anemia.
      Neither 5' nor 3' subhaplotypes of the atypical chromosomes affected Hb F levels,
      packed cell volume, or mean corpuscular volume in individuals with a Benin
      chromosome. That the 5' subhaplotype is unaffected might be a consequence of the
      small numbers of Senegal 5' subhaplotypes in our sample, the need for linkage of
      both 5' and 3' subhaplotypes of any haplotype for an effect on Hb F to be
      present, or the likelihood that a normal beta-globin gene contributed the 5'
      subhaplotypes of some atypical haplotypes.

PMID- 9766797
TI  - Usefulness of a low-dose intravenous immunoglobulin regimen for the treatment of
      thrombocytopenia associated with AIDS.
AB  - Infection with the human immunodeficiency virus (HIV) frequently is complicated
      with thrombocytopenia (HIV-Thr) during all stages of the infection. The
      treatments for autoimmune thrombocytopenic purpura (ITP) are used in HIV-Thr;
      however, their effects upon the immune status of patients with acquired
      immunodeficiency syndrome (AIDS) are unknown. Intravenous immunoglobulin (IVIg)
      is used in patients with ITP and HIV-Thr; however, its usefulness in
      thrombocytopenic AIDS patients has not been directly addressed. We used a low
      dose IVIg regimen (0.04 g/kg per week during five weeks) for the treatment of HIV
      Thr complicating AIDS. Thirteen patients received IVIg. We observed a response to
      IVIg in 13 patients by the end of week one and in 10 patients by the end of week
      five. Long-term response, evaluated three months after stopping IVIg, was present
      in four cases. IVIg was well tolerated and no opportunistic infections were
      observed during the study period. Compared with previous reports, we used 10% of
      the previously proposed dosage with an important decrease in the cost of
      treatment. Our results suggest that this low-dose IVIg regimen is a highly
      effective, nonexpensive alternative in treating HIV-Thr in AIDS. If sustained
      responses can be obtained with a similar low-dose maintenance regimen, IVIg may
      be the first choice for the treatment of HIV-Thr in AIDS patients.

PMID- 9766798
TI  - Systemic transforming growth factor-beta in patients with bone marrow fibrosis-
      pathophysiological implications.
AB  - Idiopathic myelofibrosis (IMF) and secondary myelofibrosis (MF) are characterized
      by bone marrow (BM) fibrosis, neoangiogenesis, and increased extracellular matrix
      (ECM) proteins. These characteristics may be partially attributed to transforming
      growth factor beta (TGF-beta), a cytokine produced by monocytes. In
      myelofibrosis, monocytes are increased and activated with concomitant up
      regulation of intracytoplasmic TGF-beta. We have therefore determined systemic
      TGF-beta in patients with either BM fibrosis: IMF, n = 18; MF, n = 16; or without
      BM fibrosis: hematologic disorders with normal platelets (n = 31); high platelets
      (n = 9); or normal controls (n = 27). Compared with nonfibrosis sera, there was
      significant TGF-beta elevation in BM fibrosis sera (P < 0.0001). Most (>80%) of
      the TGF-beta is active and belongs to the-beta1 isoform. In situ hybridization
      and immunohistochemical analyses in BM biopsy sections showed a marked increase
      in TGF-beta1 only in patients with fibrosis. Moreover, TGF-beta protein was
      detected mainly in myelomonocytic-like predominant areas. To determine if another
      functionally similar cytokine, basic fibroblast growth factor (bFGF), may be
      important to BM fibrosis, we quantitated sera levels and found elevation in 57%
      compared with 100% elevation for TGF-beta. The data indicate that irrespective of
      etiology, systemic TGF-beta is elevated in patients with BM fibrosis. TGF-beta
      likely plays an important role in the development of BM fibrosis. The study also
      provides a significant parameter for early therapeutic intervention in BM
      fibrosis.

PMID- 9766799
TI  - Decision-tree approach to the immunophenotype-based prognosis of the B-cell
      chronic lymphocytic leukemia.
AB  - Use of a nonlinear prediction method, such as machine learning, is a valuable
      choice in predicting progression rate of disease when applied to the highly
      variable and correlated biological data such as those in patients with chronic
      lymphocytic leukemia (CLL). In this work, decision-tree approach to cell
      phenotype-based prognosis of CLL was adopted. The panel of 33 (32 different
      phenotypic features and serum concentration of sCD23) parameters was
      simultaneously presented to the C4.5 decision tree which extracted the most
      informative of them and subsequently performed classification of CLL patients
      against the modified Rai staging system. It has been shown that substantial
      correlation between the percentage of expression of the CD23 molecule on CD19+ B
      cells, the level of sCD23, the percentage of CD45RA+, and the absolute number of
      CD4CD45RA+RO+ T-cells and the clinical stages, exists. The prediction vector,
      composed of their concatenated values, was able to correctly associate 83% of the
      cases in the low-risk group (Rai stage 0), 100% of the cases in the intermediate
      risk group (Rai stage I and II), and 89% of the cases in the high-risk group (Rai
      stage III and IV) of CLL patients. Predictivity of this vector was 100%, 95%, and
      89%, respectively. In conclusion, from the described analysis, it may be inferred
      that two processes play important roles in the progression rate of CLL:
      1.deregulated function of the CD23 gene in B-cells accompanied by the appearance
      of its cleaved product sCD23 in the sera; and 2. functionally impaired and
      imbalanced CD4 T-cell subpopulations found in the peripheral blood of CLL
      patients.

PMID- 9766800
TI  - Deficient proliferation of myeloid, erythroid, and multipotent progenitor cells
      in long-term marrow cultures from patients with aplastic anemia treated with
      immunosuppressive therapy.
AB  - By using Dexter-type long-term marrow cultures (D-LTMC), it has been shown
      previously that hematopoietic progenitor cells (HPC) from patients with aplastic
      anemia (AA) have a deficient proliferation in vitro. The studies reported to
      date, however, have focused exclusively on granulomonocytic progenitors and no
      information exists on erythroid or multipotent progenitor cells. On the other
      hand, in such studies, the input progenitor cell numbers were significantly below
      normal levels, thus suggesting that the rapid disappearance of myeloid progenitor
      cells from AA D-LTMC could also be due, at least in part, to their reduced number
      at culture onset. In the present study, we have followed the kinetics of myeloid,
      erythroid, and multipotent progenitors, from 24 AA patients subjected to
      immunosuppressive therapy (including patients that achieved complete, partial, or
      no remission at all), throughout a seven-week culture period. For analysis, we
      grouped all the patients based on their initial content of all three types of
      progenitors. Thus, we were able to evaluate separately the kinetics of these
      cells in D-LTMC from patients with normal and subnormal levels of progenitor
      cells. At the time of marrow sampling, most patients showed decreased levels of
      HPC; in fact, only 21%, 8%, and 16% of them showed normal levels of myeloid,
      erythroid, and multipotent progenitors, respectively. When cultured in D-LTMC,
      HPC from all AA patients analyzed showed a relatively fast disappearance from the
      cultures. Indeed, myeloid progenitors could be detected for only six weeks,
      whereas erythroid and multipotent progenitors disappeared from the cultures after
      two and one weeks of culture, respectively. In contrast, in normal marrow D-LTMC,
      myeloid, erythroid, and multipotent progenitors were detected for at least seven,
      five, and three weeks, respectively. Such a deficient proliferation was observed
      even in cultures of AA patients that contained normal levels of HPC at culture
      onset. Interestingly, no correlation was found between HPC proliferation in D
      LTMC and response to treatment. Thus, the results of this study indicate the
      presence of a functional in vitro deficiency in the hematopoietic system of
      patients with AA, including those that achieved partial or complete remission
      after immunosuppressive treatment. Furthermore, this work suggests that such a
      proliferation deficiency is more pronounced in erythroid and multipotent
      progenitors than in their myeloid counterparts.

PMID- 9766801
TI  - Mitoxantrone, prednimustine, and vincristine for elderly patients with aggressive
      non-Hodgkin's lymphoma.
AB  - Elderly patients with intermediate- or high-grade non-Hodgkin's lymphoma have a
      worse outcome than those who are younger than 60 years. It has been shown that
      aggressive combination chemotherapy is poorly tolerated in older patients
      resulting in a subsequent decrease in dose intensity. A phase II trial was
      conducted with mitoxantrone, prednimustine, and vincristine (NSO) in this group
      of patients. NSO consists of mitoxantrone 12 mg/M2 intravenously on day one,
      vincristine 1.4 mg/M2 intravenously on day 1 (maximum dose of two mg), and
      prednimustine 100 mg/M2 orally once a day for four days. NSO was repeated every
      21 days. Thirty-six patients were able to be evaluated. There were 18 males and
      18 females with the median age of 71 (range 60-85). NSO was well tolerated and
      nonhematological toxicities were uncommon. More than 80% of the patients received
      90% or greater of the intended dose. The complete response rate was 60.6% and
      partial response was 21.8%. At 60 months the Kaplan-Meier estimate of progression
      free survival was 47.9% (standard error 8.6%) and actual survival was 40.6%
      (standard error 8.8%). There were no differences in outcome between those with
      performance status (PS) of zero or one and those with PS > 1. NSO is well
      tolerated by elderly patients including those with PS > 1. These results compare
      favorably with other combinations in elderly patients with aggressive non
      Hodgkin's lymphoma.

PMID- 9766802
TI  - Follicular dendritic cell sarcoma and interdigitating reticulum cell sarcoma: a
      review.
AB  - Neoplasms of reticular dendritic origin are extremely rare and include the
      follicular dendritic cell sarcoma (FDCS) and the interdigitating reticulum (or
      dendritic) cell sarcoma (IDCS). In this article, we review the literature
      pertaining to the two diseases and describe clinical observations and salient
      pathologic features, including information provided by authors of FDCS and IDDCS
      reports. We performed a computerized database search for published articles
      regarding FDCS and IDDCS. The articles were evaluated critically by the authors.
      Simple descriptive statistics were used to analyze the data. There are 51 cases
      of FDCS and 21 cases of IDDCS that are well documented in the literature. The
      pathologic diagnosis of FDCS and IDDCS is often challenging and requires
      morphologic, immunophenotypic, cytochemical, and electron-microscopic analysis.
      Patients with FDCS usually present with cervical or axillary lymphadenopathy, but
      extranodal disease has been described. In at least some patients, preexisting
      Castleman's disease has been recognized. Resected localized disease may be
      prevented from recurrence by consolidative radiotherapy. Chemotherapy regimens
      have shown nondurable antitumor activity in FDCS. Patients with IDDCS usually
      present with lymphadenopathy. The clinical course of IDDCS has been variable, but
      it seems to be more aggressive than that of FDCS. Variable degrees of remission
      may be achieved with chemotherapy. FDCS and IDDCS are rare neoplasms that may
      pose difficulty in pathologic diagnosis. IDDCS seems to display a more aggressive
      behavior than FDCS. Patients with IDDCS and FDCS can eventually die of disease
      progression. The role of chemotherapy and radiotherapy is not clearly defined.

PMID- 9766803
TI  - Significance of parathyroid hormone-related protein as a factor stimulating bone
      resorption and causing hypercalcemia in myeloma.
AB  - Elevated levels of parathyroid hormone-related protein (PTHrP) in hypercalcemic
      myeloma patients were demonstrated in recent reports, suggesting that PTHrP
      behaves as a humoral mediator of hypercalcemia in myeloma. Herein we describe a
      hypercalcemic myeloma patient with a high serum PTHrP level. Moreover, the PTHrP
      level in the supernatant of bone marrow aspirates was about two-fold of that in
      serum. Reverve transcriptase-polymerase chain reaction analysis showed PTHrP m
      RNA in bone marrow containing myeloma cells. After chemotherapy, the
      concentrations of calcium and PTHrP decreased and PTHrP mRNA in bone marrow
      became undetectable. We conclude that PTHrP released by myeloma cells acted as
      the main bone resorption stimulating factor in this case.

PMID- 9766804
TI  - Successful treatment of a patient with cardiac lymphoma who presented with a
      complete atrioventricular block.
AB  - A patient with primary cardiac lymphoma, which is very rare, generally is
      regarded to have a poor prognosis. We herein report a patient with cardiac
      lymphoma who was treated successfully by systemic chemotherapy and radiotherapy
      using a pacemaker to control the complete atrioventricular (A-V) block. A 70-year
      old man had a syncope caused by a complete A-V block. An echocardiogram, a
      computed tomographic scan, and magnetic resonance imaging of his chest showed a
      cardiac tumor. At this time, a biopsy of the cardiac tumor disclosed malignant
      lymphoma (diffuse large cell type, B cell type). The patient was thus treated
      with systemic chemotherapy and radiotherapy and, as a result, achieved a complete
      remission with a disappearance of the A-V block. Recently, several successful
      outcomes involving primary cardiac lymphoma have been reported because of the
      progress in diagnostic techniques including echocardiography, computed
      tomographic scanning, and magnetic resonance imaging, as well as improvement in
      the therapy of malignant lymphoma. Our clinical experience indicated that an
      early and accurate diagnosis combined with the appropriate therapy can thus help
      in obtaining a long survival in patients with primary cardiac lymphoma.

PMID- 9766806
TI  - Malignant lymphoma in association with multiple paraffin implants.

PMID- 9766805
TI  - Familial idiopathic myelofibrosis and multiple hemangiomas.
AB  - Idiopathic myelofibrosis (MF) is a rare disease in childhood. The clinical
      spectrum is very variable. Familial idiopathic MF has been recorded
      exceptionally. In previous reports idiopathic MF in childhood has been described
      in association with congenital anomalies and with chromosome abnormalities,
      although neither of these features have been reported in a familial context. We
      report two sisters with idiopathic MF and multiple eruptive hemangiomas. Details
      of their clinical signs, laboratory findings, and histologic features are
      described.

PMID- 9766807
TI  - Bone marrow mast cell disease associated with Felty's syndrome and liver
      cirrhosis.

PMID- 9766808
TI  - Prothrombin gene 20210 G-A mutation in Turkish patients with thrombosis.

PMID- 9766809
TI  - Mechanism of activation of the GM-CSF, IL-3, and IL-5 family of receptors.
AB  - The process of ligand binding leading to receptor activation is an ordered and
      sequential one. High-affinity binding of GM-CSF, interleukin 3 (IL-3), and IL-5
      to their receptors induces a number of key events at the cell surface and within
      the cytoplasm that are necessary for receptor activation. These include receptor
      oligomerization, activation of tyrosine kinase activity, phosphorylation of the
      receptor, and the recruitment of SH2 (src-homology) and PTB (phosphotyrosine
      binding) domain proteins to the receptor. Such a sequence of events represents a
      recurrent theme among cytokine, growth factor, and hormone receptors; however, a
      number of very recent and interesting findings have identified unique features in
      this receptor system in terms of: A) how GM-CSF/IL-3/IL-5 bind, oligomerize, and
      activate their cognate receptors; B) how multiple biological responses such as
      proliferation, survival, and differentiation can be transduced from activated GM
      CSF, IL-3, or IL-5 receptors, and C) how the presence of novel phosphotyrosine
      independent signaling motifs within a specific cytoplasmic domain of betaC may be
      important for mediating survival and differentiation by these cytokines. This
      review does not attempt to be all-encompassing but rather to focus on the most
      recent and significant discoveries that distinguish the GM-CSF/IL-3/IL-5 receptor
      subfamily from other cytokine receptors.

PMID- 9766810
TI  - The molecular control of hematopoiesis: progress and problems with gene
      manipulation.
AB  - The in vitro-based discovery and characterization of hematopoietic regulators
      were of great value in identifying many of the agents active in controlling
      hematopoiesis. Subsequent in vivo studies have validated most of the information
      obtained from the in vitro studies, although the in vitro studies proved to be
      somewhat misleading in predicting which agents would exhibit the greatest
      quantitative effects in vivo. Establishing more clearly the actual situation in
      vivo has required a return to more complex, and often less satisfactory, studies
      on genetically manipulated whole animals. Of the two possible general approaches,
      gene inactivation models have proved more informative than transgenic,
      overexpression models. Each model has raised multiple questions in need of
      further resolution and the deletion studies have also indicated that other
      regulators must exist for various lineages, but have yet to be discovered. Of
      particular interest is the finding from gene inactivation studies that both G-CSF
      and thrombopoietin are necessary for the maintenance of normal numbers of
      progenitor cells in multiple lineages, suggesting that each of these lineage
      dominant regulators may have broader actions when operating on cells in the stem
      cell and progenitor cell compartments.

PMID- 9766811
TI  - Native thrombopoietin: structure and function.
AB  - Thrombopoietin (TPO), the c-Mpl ligand, is produced constitutively in liver and
      other organs, circulates in the bloodstream, and is delivered to bone marrow,
      where it stimulates the early development of multiple hematopoietic lineages and
      megakaryocytopoiesis. The concentration of TPO in blood is regulated by c-Mpl
      mass on platelets and megakaryocytes. In addition to regulation by the number of
      TPO molecules, including the possible modulation of TPO mRNA abundance in bone
      marrow, megakaryocytopoiesis and platelet production may be regulated as a result
      of modulation of TPO activity by proteolytic processing that generates truncated
      forms of the molecule. Characterization of TPO partially purified from human
      plasma, however, revealed that the full-length molecule was the predominant form
      in the blood of both normal individuals and thrombocytopenic patients, although
      small amounts of truncated species were detected. Thus, truncation of TPO, at
      least that in the circulation examined, does not appear to contribute to the
      direct regulation of platelet production in response to increased demand. Given
      that native TPO isolated from the plasma of thrombocytopenic animals comprises
      truncated forms, the truncation of TPO is likely of physiological importance in
      the life history of this molecule.

PMID- 9766812
TI  - Thrombopoietin in patients with hepatoblastoma.
AB  - Marked thrombocytosis (over 50 x 10(4)/microl) is frequently seen in patients
      with hepatoblastoma. Thrombopoietin (TPO), c-mpl ligand, has recently been
      purified as the major physiological regulator of the thrombopoiesis and is mainly
      produced in the liver. Since it is possible that TPO participates in
      thrombocytosis and the tumor growth of this particular hepatic tumor, serum TPO
      levels in addition to interleukin 1beta (IL-1beta) and IL-6 levels were assessed
      in seven untreated patients by using a sandwich enzyme-linked immunosorbent
      assay. High serum TPO levels were observed in all of the examined patients. The
      level ranged from 3.15 to 11.02 (mean +/- standard deviation; 6.08+/-1.25)
      fmol/ml. IL-6 levels were also somewhat higher than normal. Platelet counts,
      however, appeared to correlate more with serum TPO levels (p = 0.1) than with IL
      1beta (p = 0.5) and IL-6 (p = 0.2) levels. Furthermore, using the reverse
      transcriptase polymerase chain reaction method, the expression of c-mpl mRNA was
      found in five of eight hepatoblastoma tissues as well as TPO mRNA in all eight
      tissues. These observations suggest that thrombocytosis in hepatoblastoma
      patients results from the production of cytokine members, including TPO, within
      tumor tissues. Additionally, it is possible that TPO might act as a type of
      autocrine and/or paracrine system for cellular growth in this tumor.

PMID- 9766813
TI  - Insulin-like growth factor-1 (IGF-1) has a costimulatory effect on proliferation
      of committed progenitors derived from human umbilical cord CD34+ cells.
AB  - The effects of insulin-like growth factor-1 (IGF-1) on highly enriched human
      umbilical cord CD34+ cells were investigated in vitro. CD34+ cells were cultured
      in serum-free medium containing stem cell factor (SCF), GM-CSF, and interleukin-3
      (IL-3). Culture of CD34+ cells for one week in the presence of these cytokines
      resulted in a dose-dependent increase in total cell number. Addition of G-CSF
      together with SCF+IL-3+GM-CSF increased the proliferation of myelopoietic cells
      as determined by the number of cells expressing the myelomonocytic marker CD64
      and the granulocytic marker CD15 without significantly altering the number of
      CD34+ cells in the cultures. In the presence of G-CSF, IGF-1 induced a dose
      dependent increase in the total cell number and a moderate but significant
      increase in the percentages of CD15+, CD64+ cells with sustained CD34+ cell
      proliferation. We conclude that IGF-1 can enhance the in vitro proliferation of
      committed progenitor cells derived from umbilical cord CD34+ cells.

PMID- 9766814
TI  - Cell-surface antigen expression in early and term gestation fetal hematopoietic
      progenitor cells.
AB  - The objective of this study was to compare the expression of primitive cell
      surface antigens on CD34+ cells from early in gestation to those from term
      gestations. Fetal blood samples were obtained from 10 early gestation (21.0+/-0.8
      [SE] weeks) and 12 term gestation (39.3+/-0.4 weeks) fetuses. The mononuclear
      cell population was separated by red cell lysis. Two-color flow cytometry was
      used to assess cell surface antigen coexpression of CD34 with CD33, CD38, and HLA
      DR as well as staining by a cocktail of monoclonal antibodies for lineage
      associated (Lin) antigens (CD2, CD10, CD11b, CD19, CD20, CD33, CD36, 7B9, and
      Glycophorin-A). The frequency of CD34+ cells (5.5+/-0.9 versus 1.5+/-0.2, p <
      0.001) was significantly higher in the early gestational age group. Within the
      CD34+ population, the frequency of CD34+/CD38- cells (81.8+/-9.9 versus 51.3+/
      7.7, p = 0.02) and CD34+/DR- cells (15.3+/-7.4 versus 8.2+/-2.7, p = 0.05) was
      also higher in the early gestational age group. In contrast, CD34+/CD33- (51.8+/
      10.1 versus 83.0+/-6.1, p = 0.02) and CD34+/Lin- cells (15.9+/-7.0 versus 51.8 +/
      6.9, p < 0.01) were higher in the term gestation group. The high percentage of
      CD34+, CD34+/CD38-, and CD34+/DR- cells supports our hypothesis that early
      gestational age fetal blood has a higher frequency of primitive hematopoietic
      progenitor/stem cells than does umbilical cord blood at term. This suggests that
      hematopoietic progenitor/stem cells in early fetal blood may be a desirable
      target for in utero gene therapy. However, further studies to characterize the
      functional properties of CD34+ cell subsets at different stages of fetal
      development will be necessary to determine the appropriateness of targeting fetal
      hematopoietic cells for in utero gene therapy. The higher frequency of CD34+/CD33
      and CD34+/Lin- cells from term gestational age fetuses was unexpected, and the
      significance of this finding is unclear at this time.

PMID- 9766816
TI  - Progenitor cell tumors in human liver.

PMID- 9766815
TI  - Differential response of CD34+ cells isolated from cord blood and bone marrow to
      MIP-1 alpha and the expression of MIP-1 alpha receptors on these immature cells.
AB  - Macrophage inflammatory protein-1 alpha (MIP-1alpha) has been shown to have a
      role in the control of myeloid stem and progenitor cell proliferation. Recent
      evidence suggests that MIP-1alpha also has a stimulatory effect on proliferation
      of mature progenitors as well as an inhibitory effect on immature progenitors in
      vitro. We have compared the effect of MIP-1alpha on myeloid and erythroid colony
      formation of CD34+ cells isolated from bone marrow and cord blood. In the
      presence of MIP-1alpha, bone marrow granulocyte-macrophage-colony forming cells
      (GM-CFC) were inhibited over a dose range of 15 ng/ml to 500 ng/ml, and GM-CFC
      from cord blood CD34+ cells were stimulated over the same dose range. MIP-1alpha
      suppressed BFU-E colonies in both bone marrow and cord blood. Using thymidine
      suicide assays, the influence of MIP-1alpha on the cycling status of the cells
      was assessed. A good correlation between the effect of MIP-1alpha on colony
      formation and cell cycle progression was observed. These results suggest that
      there is a differential response to MIP-1alpha when bone marrow and cord blood
      CD34+ cells are compared. Using flow cytometry and a biotinylated human MIP
      1alpha/avidin fluorescein conjugate, the expression of MIP-1alpha receptors on
      CD34+ cells was assessed. The data indicated that there was little quantitative
      difference in overall expression of receptors (82.9% versus 93%) from bone marrow
      or cord blood, respectively. However, when Northern blot analysis was used, mRNA
      for two different MIP-1alpha receptors CCR1 and CCR5 could be detected in bone
      marrow, but only CCR1 mRNA was seen in cord blood CD34+ samples. Therefore, the
      expression of different receptor subtypes on CD34+ cells may be responsible for
      the difference in MIP-1alpha responsiveness observed.

PMID- 9766817
TI  - Interaction between isolated and purified liver cells and small unilamellar
      liposomes.
AB  - AIMS/BACKGROUND: The mechanism of interaction and the role played by the vesicle
      lipid composition for the selective association between liposomes and liver cells
      were studied, at the ultrastructural level, by investigating both in situ and in
      vitro the interaction between hepatocytes, Kupffer and endothelial liver cells
      with egg-phosphatidylcholine (eggPC) or eggPC/stearylamine (9:1; mol:mol) reverse
      phase evaporation (REV) liposomes. METHODS: Liver cells from rats, isolated by
      enzymatic perfusion and purified by differential centrifugation, were incubated,
      in a rotating bath at 37 degrees C, with liposomes (2.5 mM final liposomal lipid
      concentration). Cell aliquots were withdrawn and processed for electron
      microscope observation at fixed time intervals. Parallel experiments were carried
      out by in situ liver perfusion with liposome suspensions. RESULTS AND
      CONCLUSIONS: Our first conclusions are: 1) lipidic composition affects the rate
      of liposomes uptake and internalization by hepatocytes; 2) liposome uptake by
      hepatocytes or Kupffer cells is likely an endocytic process; 3) endothelial cells
      internalize lipid vesicles as well; 4) liposome uptake was due to a phagocytic
      activity for all isolated liver cells, while in the in situ observation
      endothelial cells seem to use another mechanism (fusion); and 5) the rate of
      internalization is related to the viability of the treated cells. Experimental
      data seem to indicate that differential behaviour in the internalization of lipid
      vesicles exists among parenchymal, Kupffer and endothelial liver cells. These
      differences suggest that clearance of liposomes by these cells involves two
      mechanisms (i.e., endocytosis or fusion) with different rates of uptake and
      internalization that facilitate the design of carriers that can deliver drugs
      preferentially to a specific liver cell type.

PMID- 9766819
TI  - Short-term effects of transjugular intrahepatic portosystemic shunt (TIPS) on
      functional liver plasma flow in patients with advanced cirrhosis.
AB  - AIMS/BACKGROUND: TIPS, an effective procedure applied for the treatment of
      complications of portal hypertension, is potentially followed by worsening of the
      hyperdynamic circulation of cirrhosis and the impairment of liver function. The
      aim of the present study was to evaluate short-term changes of functional liver
      plasma flow after application of TIPS, using the hepatic (extrarenal) clearance
      of D-sorbitol (S-HCl). METHODS: Twenty-five cirrhotic patients submitted to TIPS
      for prevention of variceal rebleeding entered the study. At steady-state, during
      constant infusion of a solution of D-sorbitol (25 mg/min), appropriate blood and
      urine samples were collected in order to calculate S-HCI before and 120 min after
      TIPS opening. In addition, the hepatic extraction ratio of D-sorbitol was
      directly measured at the level of the right (Er), where TIPS was applied, and of
      the left (El) hepatic veins; meanwhile the portocaval gradient (PCG) was
      registered, before and after stent dilation. A comparison of values obtained
      before and after TIPS application was performed by Student's t-test for paired
      data. RESULTS: After application of TIPS, a substantial reduction was observed in
      PCG (12.1+/-4.2 vs 24.8+/-4.3 mmHg; p<0.001) and Er values (20.6+/-14.8 vs 57.5+/
      22.3 %; p<0.001) but not El values (47.4+/-22.0 vs 53.4+/-21.4 %; p=0.178). S-HCl
      measured 120 min after TIPS opening was not statistically different from pre-TIPS
      values (389.2+/-212.1 vs 394.6+/-152.7 ml/min; p=0.892), although S-HCl
      variations in Child-Pugh class B patients were positively correlated with portal
      pressure variations (r=0.63, p=0.016). CONCLUSION: Our results demonstrate that
      in patients with advanced cirrhosis, TIPS procedure, while effective in reducing
      portal hypertension, does not lead to alterations in the functional liver plasma
      flow within the first 2 h.

PMID- 9766818
TI  - Influence of transjugular intrahepatic portosystemic shunts (TIPS) on tissue
      oxygenation in patients with cirrhosis.
AB  - AIMS/BACKGROUNDS: The aim of this prospective study was to evaluate the influence
      of transjugular portosystemic intrahepatic shunts (TIPS) on tissue oxygenation in
      patients with cirrhosis and refractory ascites. METHODS: Five shunted patients
      were included in the study. The blood and tissue oxygenation values were analyzed
      12 days and 4 months after TIPS procedure. The results were compared with those
      observed in patients treated by paracentesis. RESULTS: Unlike patients treated by
      paracentesis, PaO2 values remained unchanged throughout follow-up in shunted
      patients. After the TIPS procedure, there was a transient increase in systemic O2
      transport and O2 uptake and a transient decrease in O2 saturation of hepatic
      oxyhemoglobin. After 4 months, TIPS resulted in an increase in PCO2 values and
      bicarbonate concentrations. CONCLUSIONS: The TIPS procedure seems to prevent the
      decrease in PaO2 observed in patients treated by paracentesis and may improve the
      respiratory alkalosis of cirrhosis.

PMID- 9766820
TI  - Diaphragmatic and subcutaneous seeding of hepatocellular carcinoma following fine
      needle aspiration biopsy.
AB  - AIMS/BACKGROUND: We report the discovery of associated metastatic subcutaneous
      and metastatic diaphragmatic nodules on the needle track after fine-needle biopsy
      aspiration under echography, which has not yet been reported in the literature.
      METHODS: A 35-year-old man with non-replicating hepatitis B virus presented with
      a tumor that suggested hepatocarcinoma with cirrhosis. A diagnostic needle biopsy
      was carried out before surgery. Twelve months later, he presented with a series
      of four continuous metastatic diaphragmatic nodules on the inner wall lining the
      needle track. Surgery was performed, followed by external radiation (40 Gy).
      CONCLUSIONS: The risk of seeding following fine-needle biopsy aspiration of
      hepatocellular carcinoma can no longer be considered negligable. The real risk is
      probably underestimated. Even for biopsy of lesions localized to the inferior
      part of the liver, diaphragmatic seeding is possible. This seeding necessitates
      surgical resection, increasing the therapeutic morbidity of hepatocellular
      carcinomas. We believe that in cases where investigation of a small hepatic tumor
      suggests a hepatocellular carcinoma that could be resected, or for candidate
      patients for liver transplantation. one should not puncture the tumor. If this
      diagnostic biopsy is essential, then the needle track could be resected upon
      surgery, after cutaneous external tattooing.

PMID- 9766821
TI  - Hepatitis G virus infection in Spanish patients with hepatocellular carcinoma.
AB  - AIMS/BACKGROUND: To establish the rate of infection with a newly discovered
      Flaviviridae family member hepatitis G virus (HGV) -- in Spanish patients with
      hepatocellular carcinoma (HCC), chronic alcoholic liver disease (CALD) with
      cirrhosis, or hepatitis C virus (HCV)-induced chronic hepatitis (CH). METHODS:
      The presence of HGV-RNA was assessed in sera of 117 patients divided in three
      groups: group 1: 40 patients with HCC (35 men, mean age 62.7 years, SD 10.9
      years); group 2: 41 patients with chronic alcoholic liver disease (CALD) (36 men,
      mean age 52.5 years, SD 9.8 years); group 3: 36 patients with HCV-induced CH (27
      men, mean age 35.8 years, SD 8.5 years). Serum samples were tested for HGV-RNA by
      specific reverse transcriptase-polymerase chain reaction (RT-PCR). Serological
      markers of hepatitis B virus (HBV) and HCV were investigated in all patients and
      were negative in CALD patients, as a prerequisite for their inclusion in the
      study. All patients in group 1 were also tested for HBV-DNA. RESULTS: Rates of
      HGV-RNA positivity were, respectively, 47%, 10% and 28% in groups 1, 2 and 3.
      Differences were significant between groups 1 and 2 (p=0.00017) and groups 2 and
      3 (p= 0.042), but not between groups 1 and 3 (p=0.079). CONCLUSIONS: HGV
      infection is common in HCC patients, but usually in association with HCV,
      indicating that both agents share common routes of infection. HGV was the only
      hepatitis virus detected in 12% of HCC patients, but its possible role in the
      pathogenesis of HCC remains unclear.

PMID- 9766822
TI  - Activated sub-populations of lymphocytes and natural killer cells in normal liver
      and liver grafts before transplantation.
AB  - AIMS/BACKGROUND: The anatomic structure of the liver suggests that it is a place
      of intense trafficking between intra-hepatic and peripheral blood compartment
      leukocytes. Furthermore, the liver contains a large number of passenger
      leukocytes that may play a role in the appearance of donor-type microchimerism
      after transplantation. In this study, we aimed to define the principal lymphocyte
      sub-populations contained in donor peripheral blood and liver grafts and in
      normal liver removed during minimally invasive surgery. METHODS: Liver biopsies
      were taken at the time of vascular clampage during liver extraction from donors
      in a brain dead state (GI: n=14). Normal liver biopsies were removed during
      minimaly invasive surgery (GII: n= 10). RESULTS: We observed evidence of the
      presence of lymphocytic activation associated with the two major CD8+ lymphocyte
      and natural killer (NK) cell populations in the two groups, with a significant
      increase in TCRgammadelta-bearing lymphocyte receptors between normal liver and
      the liver graft. CONCLUSIONS: The presence of activated leukocytes in the graft
      could have a fundamental role in induction of peripheral tolerance. This
      activation could be the result of a basic immunological response linked to the
      interaction of T cells and NK cells, and of secondary activation due to stress
      and the conditions necessary for organ removal from donors in a brain dead state.

PMID- 9766824
TI  - Replication error frequencies in primary hepatocellular carcinoma: a comparison
      of solitary primary versus multiple primary cancers.
AB  - AIMS/BACKGROUND: Replication errors (RERs) at microsatellite loci are associated
      with the development of not only hereditary nonpolyposis colon cancer but also
      sporadic cancers. To examine the association between RERs and human
      hepatocarcinogenesis, we looked for microsatellite instability in solitary and
      multiple primary hepatocellular carcinomas (HCCs). METHODS: DNAs were extracted
      from 34 solitary primary HCCs and 14 HCCs with multiple primary cancers. Twelve
      microsatellite alleles were amplified by PCR from the DNAs, and RERs were
      assessed by their mobility shift. RESULTS: RERs were found in only two cases (6%)
      of solitary HCC and four cases (29%) of HCC with multiple primary cancers. Two of
      the four HCCs with multiple primary cancers showed RERs at two and three
      microsatellite loci, respectively. Of 12 microsatellite loci examined, TP53 and
      D16S476 sensitively detected RERs in HCCs with multiple primary cancers, at a
      frequency of 23% and 33%, respectively. CONCLUSIONS: RERs are rarely associated
      with carcinogenesis in human primary HCC, and RER-related genetic alterations may
      be associated with a part of HCC with multiple primary cancers. If future studies
      confirm this association, then the two probes TP53 and D16S476 may be useful for
      the prediction of development of multiple primary cancers with HCC.

PMID- 9766823
TI  - Hepatic metabolism of oxidatively modified apo E-free high-density lipoproteins.
AB  - AIMS/BACKGROUND: The metabolism of rat apo E-free high-density lipoproteins (HDL)
      was contrasted with oxidatively modified apo E-free high-density lipoproteins (OX
      HDL) in the rat hepatoma cell, Fu5AH. RESULTS: When 10-100 microg/ml [125I]-HDL
      or [125I]-OX-HDL were incubated with cells for 4 h at 37 degrees C, cellular
      uptake of oxidized lipoproteins was twice control. In contrast, protein
      degradation was equal. [125I]-HDL or [125I]-OX-HDL were incubated with the cells
      for 4 h followed by a 4 h chase with unlabeled HDL and OX-HDL, respectively. In
      these experiments, 80% of [125I]-HDL was resecreted from the cell within 30 min
      while 50% of [125I]-OX-HDL was retained by the cell after 2 h. Electron
      microscopy was used to determine if the OX-HDL was retained in lysosomes. Cells
      were incubated with gold-labeled OX-HDL, and lysosomes were stained with acid
      phosphatase. Gold-labeled OX-HDL was abundant in intracellular vesicles that were
      not reactive to acid phosphatase. However, vesicles with a high content of OX-HDL
      frequently stained positively for 3,3'-diaminobenzidine, a stain that reacts with
      catalase and is used to detect peroxisomes. CONCLUSIONS: The present evidence
      indicates that the cellular metabolism of OX-HDL is different from that of
      unmodified HDL.

PMID- 9766825
TI  - Cell-kinetic study of proliferating bile ductules in various hepatobiliary
      diseases.
AB  - AIMS AND METHODS: Proliferat bile ductules are classifiable histologically into
      typical and atypical types. To clarify their histogenesis and regulation, we
      examined their phenotype, proliferating and degrading characteristics, using
      liver sections from 58 patients with various hepatobiliary diseases. RESULTS:
      Typical ductules were found in all cases. Atypical ductules were also frequently
      found in extrahepatic biliary obstruction (EBO), chronic hepatitis (CH), as well
      as in primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC).
      Typical ductules completely expressed biliary-type cytokeratins, while atypical
      ductules lacked complete biliary-type cytokeratins and often connected with
      periportal hepatocytes. Proliferative indices of typical ductules in diseased
      livers were higher than those in normal livers, while those of atypical ductules
      were low in PBC and PSC and high in EBO and CH. Apoptosis was detected in typical
      and atypical ductules. Perforin was preferably expressed on typical and atypical
      ductules, compared with CD95. CONCLUSIONS: These findings suggest that typical
      ductules reflect active proliferation of preexisting ductules. Atypical ductules
      might be classifiable into two categories: those in PBC and PSC primarily reflect
      ductular transformation (metaplasia) of periportal hepatocytes, while those in
      EBO and CH reflect active proliferation and transformation of hepatocytes.
      Apoptosis via perforin/granzyme B pathway may be involved in the maintenance of
      homeostasis in ductular proliferation as degrading fraction.

PMID- 9766826
TI  - Diagnosis of hepatopulmonary syndrome with contrast transthoracic
      echocardiography and histological confirmation.
AB  - We report a patient with cirrhosis and hepatopulmonary syndrome. This syndrome is
      an entity characterized by anomalies in the arterial oxygenation in patients with
      chronic hepatic disease and/or portal hypertension and demonstration of pulmonary
      vasodilatation (PV) in absence of primary cardiac or pulmonary disease. We show
      that the finding of PV with transthoracic contrast enhanced echocardiography
      (TCEE) in the diagnosis of PV is real and corresponds to direct measurement of
      capillary diameter by morphometry.

PMID- 9766827
TI  - Primary liver tumour of intermediate (hepatocyte-bile duct cell) phenotype: a
      progenitor cell tumour?
AB  - A 57-year-old female patient presented with painless obstructive jaundice and
      mild mesogastric pain; she was in good general condition on admission. Abdominal
      ultrasonography revealed diffuse tumoral invasion of the liver, suggesting
      diffuse metastases. A liver biopsy showed a tumour with a trabecular growth
      pattern, composed of uniform relatively small cells, very suggestive of an
      endocrine carcinoma. Additional immunohistochemical stains, however, did not show
      any endocrine differentiation, but showed positivity for both hepatocyte-type
      cytokeratins (cytokeratin 8 and 18) and bile duct-type cytokeratins (cytokeratin
      7 and 19). In addition, parathyroid hormone-related peptide, shown to be a good
      marker for cholangiocarcinoma, was immunoreactive. Electron microscopy revealed
      tumour cells with an intermediate phenotype: the cells clearly showed hepatocyte
      features on one hand and bile duct cell features on the other hand. Nine days
      after admission, the patient died due to liver failure and hepatic
      encephalopathy. Autopsy excluded another primary tumour site. Overall, this
      tumour was a primary liver tumour with an intermediate phenotype and with a very
      rapid clinical course. The intermediate (between hepatocyte and bile duct cell)
      phenotype suggests an immature progenitor cell origin, which is concordant with a
      rapid clinical course. This type of tumour has not been described previously and
      provides additional evidence for the existence of progenitor cells in human
      liver.

PMID- 9766828
TI  - Paracetamol-induced liver toxicity after intravenous administration.

PMID- 9766829
TI  - Transgenic studies of pain.
AB  - A revolution in molecular biological technology has allowed, for the first time,
      the study of pain at the level of the gene. The molecular genetic technique
      currently garnering the most interest is the use of transgenic mice that either
      overexpress, or do not express, presumably pain-related proteins. This paper
      reviews the findings of investigations in which a transgenic mouse has been
      assessed for nociceptive or analgesic sensitivity. As of this writing, 25
      different kinds of mutant mice--lacking neurotrophins and their receptors,
      peripheral mediators of nociception and hyperalgesia, opioids and their
      receptors, non-opioid transmitter receptors, and intracellular molecules
      participating in signal transduction--have been produced and tested on behavioral
      assays of nociception. Results of these studies have been variously confirmatory,
      contradictory and enlightening compared to conventional investigations. The
      advantages and limitations of this approach to pain research are discussed.

PMID- 9766830
TI  - Transient inhibition of responses to thermal stimuli of spinal sensory tract
      neurons in monkeys during sensitization by intradermal capsaicin.
AB  - A secondary zone of cutaneous hyperalgesia in humans is characterized by
      increased pain to mechanical stimuli. In contrast, the perception of heat stimuli
      delivered to a secondary zone of hyperalgesia in humans often shows a paradoxical
      decrease in magnitude. A number of studies have shown that the responses of
      spinal cord neurons to cutaneous mechanical stimuli after peripheral injury model
      well the mechanical hyperalgesia. However, the responses of dorsal horn neurons
      to thermal stimuli after peripheral injury have not been as carefully studied.
      The present study examined the effects of intradermal capsaicin on the responses
      of spinal sensory projection neurons to cutaneous mechanical and thermal stimuli.
      Our observations indicate that the responses of identified sensory projection
      neurons to heat are transiently reduced at the same time that responses of these
      cells to mechanical stimuli are increased. These results confirm a role for
      sensory projection cells in signaling the sensory discriminative aspects of pain
      in humans and underscore the emerging complexity of dorsal horn circuitry and
      sensory processing.

PMID- 9766831
TI  - Memories of chronic pain and perceptions of relief.
AB  - Clinicians and researchers often ask patients to remember their past pain. They
      also use patient's reports of relief from pain as evidence of treatment efficacy,
      assuming that relief represents the difference between pretreatment pain and
      present pain. We have estimated the accuracy of remembering pain and described
      the relationship between remembered pain, changes in pain levels and reports of
      relief during treatment. During a 10-week randomized controlled clinical trial on
      the effectiveness of oral appliances for the management of chronic myalgia of the
      jaw muscles, subjects recalled their pretreatment pain and rated their present
      pain and perceived relief. Multiple regression analysis and repeated measures
      analyses of variance (ANOVA) were used for data analysis. Memory of the
      pretreatment pain was inaccurate and the errors in recall got significantly worse
      with the passage of time (P < 0.001). Accuracy of recall for pretreatment pain
      depended on the level of pain before treatment (P < 0.001): subjects with low
      pretreatment pain exaggerated its intensity afterwards, while it was
      underestimated by those with the highest pretreatment pain. Memory of
      pretreatment pain was also dependent on the level of pain at the moment of recall
      (P < 0.001). Ratings of relief increased over time (P < 0.001), and were
      dependent on both present and remembered pain (Ps < 0.001). However, true changes
      in pain were not significantly related to relief scores (P = 0.41). Finally,
      almost all patients reported relief, even those whose pain had increased. These
      results suggest that reports of perceived relief do not necessarily reflect true
      changes in pain.

PMID- 9766833
TI  - Menstrual cycle modulation of tender points.
AB  - Changes in pain sensitivity throughout the menstrual cycle were assessed in 36
      normally menstruating women and 30 users of oral contraceptives. Pain sensitivity
      was measured with palpation of rheumatological tender points and with pressure
      dolorimetry. The number of tender points identified by palpation was greater in
      the follicular (postmenstrual) phase of the cycle as compared to the luteal
      (intermenstrual) phase in normally cycling women but not in users of oral
      contraceptives. These findings are related to previously described physiological
      and psychological features of the menstrual cycle, with particular emphasis on
      the role of hormonal events in modulating pain perception, particularly in
      musculoskeletal disorders such as fibromyalgia.

PMID- 9766832
TI  - Sex differences in response to cutaneous anesthesia: a double blind randomized
      study.
AB  - The existing literature on experimentally induced pain indicates that there are
      sex differences, with females displaying greater sensitivity. In epidemiological
      studies, sex differences are also noted in the prevalence of a number of pain
      syndromes, with females reporting more severe pain, more frequent pain, and pain
      of longer duration. Complicating the interpretation of pain differences between
      men and women in clinical samples are reports of sex differences in response to
      pain-reducing medications. Studies in human subjects suggest that women respond
      better to certain opioid analgesics than men following third molar extraction,
      but few studies have assessed sex effects in effectiveness of topical
      anesthetics. The purpose of this study was to test for sex differences in
      response to a topical anesthetic, Lidocaine, using double blind, placebo
      controlled experimental methodology, in combination with a magnitude matching
      psychophysical protocol using a pressure algometer. The subjects were 21 female
      and 23 male adult volunteers. Twenty-four subjects (12 males and 12 females) were
      randomly assigned to the Lidocaine condition and 20 subjects were randomly
      assigned to the placebo control condition (9 males and 11 females). The effect
      size across sex for subjects in the Lidocaine treatment condition on the response
      bias variable was large indicating the males rated the stimuli as less painful
      than the females. Sex differences were not observed for discriminability in the
      Lidocaine treatment condition. This study did not show sex differences in the
      placebo condition. These results are particularly interesting in light of
      previous work that has shown similar pain stimuli (pressure pain) to be the
      stimulation most sensitive to sex differences. Results of this study suggest that
      the protocol employed (pressure pain stimulus with magnitude matching task) is
      sensitive to both anesthetic treatment and sex differences and represents an
      improvement in pain assessment methodology for use in experimental studies and in
      the clinic.

PMID- 9766834
TI  - Sex differences in opioid and N-methyl-D-aspartate mediated non-opioid biting fly
      exposure induced analgesia in deer mice.
AB  - There is evidence for sex differences in responses to noxious stimuli and in the
      expression and mediation of analgesia. In particular, results of investigations
      with swim stress and the more ethologically appropriate stress of predator odor
      exposure have suggested sex differences in N-methyl-D-aspartate (NMDA) receptor
      system involvement in the mediation of analgesia. Whether or not this sex
      difference generalizes to other environmental stressors is, however, not clear.
      Biting flies are a natural aversive stimuli commonly encountered by wild and
      domestic animals and humans. The present study examined the opioid and non-opioid
      mediated nociceptive (50 degrees C hot plate) responses of reproductive male and
      female deer mice, Peromyscus maniculatus, exposed to biting fly attack. A 30 min
      exposure to biting flies (stable flies, Stomoxys calcitrans (L.)) elicited a
      naloxone sensitive, opioid-mediated analgesia that was of a greater magnitude in
      males than in female deer mice. In contrast, a 5 min exposure to biting flies
      elicited a 'on-opioid' analgesia that was of similar magnitude in both sexes and
      insensitive to both naloxone and the specific kappa opiate antagonist, nor
      binaltorphimine. In male mice this non-opioid analgesia was antagonised by the
      competitive NMDA antagonist, NPC 1262, while in reproductive females the biting
      fly-induced analgesia was insensitive to NPC 12626. These results show that there
      are sex differences in NMDA involvement in the mediation of the non-opioid
      analgesia arising from brief exposure to the stress of biting fly attack. These
      data from a common, natural environmental challenge support the presence of basic
      sex difference in NMDA involvement in the mediation of stress-induced analgesia.

PMID- 9766835
TI  - Wallerian degeneration and hyperalgesia after peripheral nerve injury are
      glutathione-dependent.
AB  - Experimental inflammatory compression injury to the sciatic nerve (chronic
      constriction injury, CCI) induces Wallerian degeneration of axons and damages non
      neuronal cells at the injury site in association with the development of
      exaggerated pain-like behavior, or hyperalgesia, to noxious thermal stimuli in
      the affected anatomical area. We examined whether glutathione, one of whose many
      functions is an important endogenous antioxidant, influenced resulting
      neuropathology and hyperalgesia following CCI. Dietary supplementation of the
      amino acid N-acetyl-cysteine (NAC), a rate-limiting component of glutathione
      production, beginning 1 day prior to CCI significantly diminished both Wallerian
      degeneration, measured by quantitative morphometry of myelinated fibers, and
      thermal hyperalgesia. NAC treatment raised nerve glutathione levels compared to
      untreated nerves, as indicated using hemeoxygenase-1 (hsp32) immunoreactivity as
      a marker of glutathione depletion. Because NAC is also known to have antioxidant
      abilities, studies simultaneously inhibited glutathione synthesis, and results
      demonstrated no significant reduction in resulting neuropathology or
      hyperalgesia. Delaying NAC administration to post-injury times consistently
      decreased hyperalgesia, although not significantly. This study identifies
      glutathione levels, and presumably oxidative stress, as important determinants of
      the neuropathological and behavioral consequences of nerve injury, and suggests
      that dietary supplementation of NAC constitutes an effective pre-emptive
      therapeutic strategy for situations involving painful nerve injury, such as
      occurs during surgery.

PMID- 9766836
TI  - Spinal bicuculline produces hypersensitivity of dorsal horn neurons: effects of
      excitatory amino acid antagonists.
AB  - In this study, we sought to characterize the effects of focal GABA(A) receptor
      antagonism on spontaneous and evoked activity in dorsal horn neurons of the alpha
      chloralose anesthetized cat. Bicuculline (0.5, 1.0 mM) applied near the neurons
      through a transparenchymal dialysis fiber resulted in increased evoked activity
      in nociceptive dorsal horn neurons. Hair deflection was the stimulus most
      affected, followed by both low and high threshold tonic mechanical stimulation of
      the receptive field. In addition, neurons displayed increased background
      discharge and a subpopulation developed an increased afterdischarge to noxious
      mechanical stimulation. This is in contrast to our previous work with glycine
      receptor antagonism where only the evoked response to hair follicle activation
      was significantly enhanced. Subsequent co-administration of an NMDA receptor
      antagonist (AP-7, 2.0 mM) was without any apparent effect on either basal or
      bicuculline-enhanced responses. Co-administration of a non-NMDA excitatory amino
      acid receptor antagonist (CNQX, 1.0 mM) with the bicuculline non-selectively
      blocked both low and high threshold mechanical input. The inability of AP-7 to
      reverse the bicuculline-associated hyperreactivity also contrasts with the AP-7
      reversal of the strychnine-associated hyperreactivity. These results point out
      that, while GABA and glycine are frequently co-localized in cells of the spinal
      dorsal horn and both appear to mediate tonic inhibitory control systems, they are
      not at all equivalent and are subject to different modulatory pharmacologies.
      Removal of each influence may model a different component of neuropathic pain.

PMID- 9766837
TI  - Sensory changes in the territory of the lingual and inferior alveolar nerves
      following lower third molar extraction.
AB  - Post-injury inflammation activates nociceptive systems and recruits normally non
      nociceptive afferents into a pain processing role. During inflammation, Abeta low
      threshold mechanoreceptor afferents that usually mediate tactile sensation
      acquire properties of nociceptors, allowing them to participate in post-injury
      spontaneous pain and evoked abnormalities such as tenderness and pain to light
      touch. This study assessed the sensory consequences of post-injury inflammation
      following extraction of a single, lower third molar tooth. Extensive bilateral
      evaluations were performed in the territory of nerves assumed to be exposed to
      both inflammation and mechanical trauma, inflammation alone, or only the central
      consequences of peripheral inflammation. Testing at the distal termination of
      nerves assumed to be exposed to local inflammation (mental and lingual nerve
      territory) revealed decreased detection thresholds (P < 0.05) to electrical
      stimulation and to mechanical stimulation by sensitive, disposable filaments
      developed and validated for this application. Testing at sites of assumed
      inflammation and mechanical trauma (mental nerve territory) showed reduced pain
      thresholds to electrical stimulation. Thermal detection and pain thresholds were
      not altered at any location in patients, and no effects were observed in control
      subjects receiving only local anesthetic injections. These results in humans are
      consistent with recent experimental evidence that inflammatory processes alter
      the central consequence of activity in large-diameter Abeta touch primary
      afferents evoked under natural conditions by gentle mechanical stimulation. These
      effects result in hyperesthesia, increased sensitivity to light touch, and
      mechanical allodynia, pain evoked by normally innocuous stimulation of Abeta
      primary afferents.

PMID- 9766838
TI  - Predictive factors for 1-year outcome of low-back and neck pain in patients
      treated in primary care: comparison between the treatment strategies chiropractic
      and physiotherapy.
AB  - The inability to predict outcome in patients with low back/neck pain leads to
      inappropriate or unnecessary treatment. The aims of the study were to identify
      prognostic factors for disability at 1-year follow-up in patients with back pain
      visiting primary care, and to compare the effect of these in two treatment
      strategies--chiropractic and physiotherapy. Data were taken from a randomised
      trial on patients with back/neck pain visiting the general practitioner, in which
      patients were allocated to chiropractic and physiotherapy as primary management.
      Three hundred and twenty-three patients, aged 18-60 years, who had no
      contraindications to manipulation and who had not been treated within the
      previous month were included in the study. Multiple regression analysis was used
      to identify prognostic factors. Dependent variables were mean Oswestry score and
      mean change in Oswestry score at 12-month follow-up. The multiple regression
      analysis revealed five significant (P < 0.001-0.01) prognostic factors; duration
      of current episode, Oswestry score at entry, expectations of treatment, number of
      localisations, and well-being. Besides, the regression coefficients for the
      significant factors were compared between the two treatment strategies. No
      significant difference in effect or regression coefficients for the prognostic
      factors were seen between the two treatment strategies. Twelve per cent of the
      patients had poor prognostic factors (duration > or = 1 month, more than one
      localisation, low expectations of treatment and low well-being) at entry. These
      patients had a mean Oswestry score above 20% at 1-year follow-up. Clinical
      decision models for the management of patients with back pain visiting primary
      care that consider prognostic factors need to be implemented and prospectively
      evaluated.

PMID- 9766839
TI  - Phantom sensations following acute pain.
AB  - In human amputees with painful phantom sensations, mislocalizations of tactile
      stimuli to the phantom increase with the amount of cortical representational
      reorganization and the extent of phantom pain. A similar phenomenon was
      incidentally encountered in healthy subjects. For reasons unrelated to the
      question of mislocalization, we performed a study involving the application of
      experimental acute pain to the hand followed by non-noxious tactile stimulation
      of the ipsilateral lip. During lip stimulation, two out of six subjects
      spontaneously reported perceiving an additional phantom-like sensation in the
      hand synchronously to the non-noxious lip stimulation. Similar, although more
      diffuse, phantom sensations were observed in two out of seven additional subjects
      who were then tested specifically for this effect. The observation is compatible
      with a pain-induced hyperresponsiveness of the cortical hand area to
      somatotopically adjacent inputs from the lip. This suggests that, even in the
      absence of deafferentation, pain can lead to a representational reorganization.

PMID- 9766840
TI  - Chronic gynaecological pain: an exploration of medical attitudes.
AB  - Women with chronic pelvic pain experience serious distress and lifestyle
      disruption. Confronted with a difficult condition to diagnose and treat
      effectively, doctors express a negative perception of this group of 'heartsink'
      patients. This study aimed to characterise medical attitudes towards the
      treatment of women with chronic pelvic pain. Tape recorded focus group
      discussions with gynaecologists, general practitioners and patients were
      transcribed and analysed using ethnographic software to identify themes. A postal
      questionnaire was sent to 300 British gynaecologists of which 145 were returned
      (48%). Principal components analysis identified five factors accounting for 32.4%
      of the variance, labelled 'efficiency', 'complexity', 'socio-cultural
      liberalism', 'pathology' and 'communication'. Scores for 'socio-cultural
      liberalism' were higher among gynaecologists in the younger age groups, women,
      and those giving their ethnic origin as Caucasian. Scores for 'pathology' were
      lower among younger gynaecologists. A sex difference just failed to reach
      statistical significance. Multiple linear regression confirmed significant
      independent relationships with scores for 'socio-cultural liberalism' and
      respondent sex, ethnicity and age group under 38 years.

PMID- 9766841
TI  - Estrogens and the myth of male privilege.

PMID- 9766842
TI  - Molecular and clinical aspects of neutrophil peroxidase deficiency:
      multidisciplinary approaches on an international scale.

PMID- 9766843
TI  - Insights into myeloperoxidase biosynthesis from its inherited deficiency.
AB  - Myeloperoxidase (MPO) is a heme protein present in the granules of neutrophils
      and monocytes. The activated neutrophil releases MPO into the phagolysosome or
      into the extracellular space in response to a variety of agonists. During
      concomitant activation of the NADPH-dependent oxidase, the stimulated neutrophil
      also generates hydrogen peroxide, and in this way the MPO-hydrogen peroxide
      halide system exerts its potent microbicidal activity. Recent interest in MPO has
      extended well beyond the domain of innate host defense against infection and
      includes generalized inflammatory diseases, atherosclerosis, and degenerative
      neurologic diseases. Search of the various data banks using the cDNA sequence for
      MPO has uncovered previously unsuspected relationships among peroxidatively
      active proteins in widely different species. In addition, application of the
      analytical tools of cell and molecular biology has allowed definition of specific
      genotypes underlying MPO deficiency and the impact of particular mutations on the
      fate of MPO precursors along the biosynthetic pathway. In parallel, such studies
      have allowed significant advances in understanding of the normal steps in MPO
      biosynthesis and intracellular targeting.

PMID- 9766844
TI  - Prevalence of myeloperoxidase deficiency: population studies using Bayer
      Technicon automated hematology.
AB  - The Bayer-Technicon hematological devices differentiate leukocytes by their
      peroxidase activity and their volume, displaying them as separate clusters.
      Peroxidase deficiencies are manifested by the irregular location of these
      clusters. This makes it possible to identify persons totally or partially lacking
      myeloperoxidase. The deficiency is quantified by the myeloperoxidase index, which
      is expressed for every routine analysis and for which normal values were
      determined. Values of the myeloperoxidase index confirm varying degrees of
      deficiency and prevalence. Family studies using these degrees show that the
      hereditary pattern must be more complicated than the classical autosomal
      recessive mode. A bigenic mode is suggested. While about half of the totally
      deficient individuals detected were free of typical symptoms, in the other half
      we found infectious complications that were sometimes life-threatening. The
      hematological devices allow the identification of persons suffering from
      eosinoperoxidase deficiency and from MPO deficiency of the monocytes. The latter
      symptom seems to indicate immaturity of these cells and may lead to unexpected
      diagnosis of malignancy.

PMID- 9766845
TI  - Clinical manifestation of myeloperoxidase deficiency.
AB  - Myeloperoxidase (MPO), an iron-containing heme protein localized in the
      azurophilic granules of neutrophil granulocytes and in the lysosomes of
      monocytes, is involved in the killing of several micro-organisms and foreign
      cells, including bacteria, fungi, viruses, red cells, and malignant and
      nonmalignant nucleated cells. Despite the primary role of the oxygen-dependent
      MPO system in the destruction of certain phagocytosed microbes, subjects with
      total or partial MPO deficiency generally do not have an increased frequency of
      infections, probably because other MPO-independent mechanism(s) for microbicidal
      activity compensate for the lack of MPO. Infectious diseases, especially with
      species of Candida, have been observed predominantly in MPO-deficient patients
      who also have diabetes mellitus, but the frequency of such cases is very low,
      less than 5% of reported MPO-deficient subjects. Evidence from a number of
      investigators indicates that individuals with total MPO deficiency show a high
      incidence of malignant tumors. Since MPO-deficient PMNs exhibit in vitro a
      depressed lytic action against malignant human cells, it can be speculated that
      the neutrophil MPO system plays a central role in the tumor surveillance of the
      host. However, any definitive conclusion on the association between MPO
      deficiency and the occurrence of cancers needs to be confirmed in further
      clinical studies. Clinical manifestations of this disorder depend on the nature
      of the defect; an acquired abnormality associated with other hematological or
      nonhematological diseases has been occasionally described, but the primary
      deficiency is the form more commonly reported. Another area of interest pertinent
      to MPO expression is related to the use of anti-MPO monoclonal antibodies for the
      lineage assignment of acute leukemic cells, the definition of FAB MO acute
      myeloid leukemia, the identification of biphenotypic acute leukemias, and their
      distinction from acute leukemia with minimal phenotypic deviation. The advantage
      of MPO monoclonal antibodies over the MPO cytochemical assay relies in the
      ability of the former method to recognize the enzymatically inactive precursor
      forms of MPO.

PMID- 9766847
TI  - Molecular genetics of peroxidase deficiency.
AB  - Myeloperoxidase (MPO) belongs to a family of related proteins which also includes
      eosinophil, thyroid, and lactoperoxidase. The MPO gene is a 14-kb gene located on
      the long arm of chromosome 17. Thus far four mutations (R569W, Y173C, M251T and a
      14-base deletion in exon 9) have been identified in patients with MPO deficiency.
      As in other genetically determined diseases, many more mutations will eventually
      be revealed that cause this disease. Present evidence shows that most patients
      are compound heterozygotes, i.e., they have inherited different mutations on
      their paternal and maternal MPO alleles. Understanding why some patients with
      this genetic deficiency develop clinical symptoms while others do not requires
      mutation analyses of a large number of patients. This includes the analysis of
      genotype-phenotype relationships. Genotyping has also been started in patients
      with EPO-deficiency.

PMID- 9766846
TI  - Autoantibodies to myeloperoxidase: clinical and pathophysiological significance.
AB  - Autoantibodies to MPO are associated with various forms of systemic vasculitis,
      including the renal limited form described as idiopathic crescentic
      glomerulonephritis. In vitro the antibodies are able to further activate primed
      neutrophils to the production of reactive oxygen species and the release of
      lysosomal enzymes. In vivo experimental studies in which an autoimmune response
      to MPO was induced in rats have demonstrated the in vivo potential of the
      autoantibodies to aggravate subclinical inflammatory lesions. In the right
      context, vasculitis and glomerulonephritis can ensue. Further studies are being
      directed to the precise characterization of autoimmune responses in order to
      obtain clues for the etiopathogenesis of the associated diseases.

PMID- 9766848
TI  - The influence of antigenic variation on cytotoxic T lymphocyte responses in HIV-1
      infection.
AB  - The propensity of HIV-1 for genetic variation, a consequence of error-prone
      reverse transcription combined with high rates of replication, is thought to
      contribute to the establishment of persistent infection in the host despite the
      presence of a vigorous antiviral immune response. Protective immunity to viruses
      is mediated primarily by cytotoxic T lymphocytes, which recognize viral peptides
      of 8-11 amino acids bound to major histocompatibility complex class I molecules
      on the surface of infected cells. In this review we examine the mechanisms by
      which mutation within peptide antigen-encoding regions of the viral genome
      enables HIV-1 to evade recognition by virus-specific cytotoxic T lymphocytes. The
      discussion is relevant to other genetically unstable viruses and more generally
      to intracellular pathogens of variable antigenicity.

PMID- 9766849
TI  - Estradiol enhances gene delivery to human breast tumor cells.
AB  - The influence of estradiol on the delivery of plasmid DNA to estrogen receptor
      positive MCF-7 human breast cancer cells was studied by the use of a reporter
      assay and by histochemical staining. Continuous exposure to estradiol enhanced
      the lipofectamine-mediated delivery of both pSV40-luciferase and pCMV beta
      galactosidase in a concentration-dependent manner. Estradiol increased both the
      amount of pCMV beta-galactosidase per cell and the total fraction of cells
      competent to receive the transgene. The efficiency of transgene delivery to MCF-7
      cells was further improved by repeating the transfection procedure in the
      presence of estradiol. Although overall gene uptake was reduced in control cells
      when studies were performed at room temperature (as opposed to 37 degrees C),
      potentiation of gene uptake by estradiol was maintained. At a concentration of
      100 microM, estradiol also enhanced delivery of the transgene to estrogen
      receptor negative MDA-MB-231 breast tumor cells, indicating that the potentiating
      effects of estradiol are not mediated through the estrogen receptor. These
      studies are the first to raise the possibility that gene delivery to breast tumor
      cells can be improved by estradiol in single- or repeated-treatment regimens.

PMID- 9766850
TI  - Simultaneous occurrence of various mutations and polymorphisms in cis and in
      trans of the galactose-1-phosphate uridyltransferase gene in a Turkish family
      with classical galactosemia.
AB  - Classical galactosemia, characterized clinically by acute hepatic dysfunction,
      sepsis, cataract, and failure to thrive, is caused by deficiency of galactose-1
      phosphate uridyltransferase (GALT). Galactose restriction normalizes these acute
      symptoms; however, long-term complications such as intellectual deficits and
      ovarian failure are conspicuous in the majority of patients. Here we report two
      Turkish siblings with classical galactosemia. The clinical course of the two
      children differed markedly: only the older girl suffered from severe acute
      symptoms during the neonatal period, and she developed greater mental retardation
      than her younger affected brother. The functional activity of GALT was virtually
      absent in each affected children. The mother and two healthy siblings exhibited
      approximately 50% normal GALT activity and the father approximately 25%.
      Molecular analysis revealed that these two galactosemic siblings were homozygous
      for a stop codon mutation of E340X in GALT exon 10. Moreover, two additional
      mutations, a neutral polymorphism L218L and N314D, which are typical for the
      Duarte-I variant, were found in the same GALT allele. The two healthy siblings
      and the parents were heterozygous for these combinations of mutations. In
      addition, the father's second GALT allele revealed three intron mutations at
      nucleotide position 1105 (G-->C), 1323 (G-->A) and 1391 (G-->A) and the N314D
      mutation, which correspond to the mutations of Duarte-2 variant. Our findings
      indicate that in classical galactosemia several distinct mutations can be present
      in one allele (in cis) of the GALT gene. Therefore it seems to be necessary to
      examine all introns and exons of the GALT gene in galactosemic patients who do
      not carry the Q188R mutation or another frequent mutation in the GALT gene.

PMID- 9766852
TI  - Determination of the molecular species composition of diacylglycerols in human
      adipose tissue by solid-phase extraction and gas chromatography on a polar phase.
AB  - The free diacylglycerols (DAGs) in adipose tissue are involved in the metabolism
      of stored lipids and hence are related to the supply of fatty acids for other
      tissues. This paper describes a simple, fast, and reproducible method for the
      identification and quantification of different molecular species of DAGs in human
      adipose tissue. The method comprised solid-phase extraction on a diol-bonded
      phase column combined with capillary GC analysis of silylated DAG derivatives on
      a polar phase (65% phenylmethylsilicone). Separation of the DAGs was achieved
      based on chain length, isomeric structure (1,2- and 1,3-DAGs), and degree of
      unsaturation. The main DAGs were 1,2-OO, 1,2-OP, 1,2-LO and 1,2-LP. The
      composition was corroborated by analysis of the component fatty acids of the
      DAGs, 18:1(n-9), 16:0, and 18:2(n-6) being the three major fatty acids obtained.

PMID- 9766853
TI  - Liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry
      of omega- and (omega-1)-hydroxylated metabolites of elaidic and oleic acids in
      human and rat liver microsomes.
AB  - In order to characterize the nature of the active site of cytochrome P450 2E1,
      the metabolism of various fatty acids with cis/trans geometric configurations has
      been investigated. A system coupling atmospheric pressure chemical ionization
      mass spectrometry detection with HPLC separation was developed as an alternative
      method for the characterization of hydroxylated metabolites of oleic and elaidic
      acids in rat and human liver microsomes. Oxidation of oleic and elaidic acids led
      to the formation of two main metabolites which were identified by LC-MS and GC-MS
      as omega and (omega-1)-hydroxylated (or 17-OH and 18-OH) fatty acids, on the
      basis of their pseudo-molecular mass and their fragmentation. The assay was
      accurate and reproducible, with a detection limit of 25 ng per injection, a
      linear range from 25 to 1128 ng per injection, no recorded interference, intra
      day and inter-day precision with variation coefficients <14%. This LC-MS method
      was validated with oleic acid by using both radiometric and mass spectrometric
      detections. A significant correlation was found between the two methods in human
      (r=0.86 and 0.94 with P<0.05 and 0.01) and rat liver microsomes (r=0.90 and 0.85
      with P<0.01 and 0.05) for 17-OH and 18-OH metabolites, respectively. HPLC coupled
      to mass spectrometry for the analysis of hydroxylated metabolites of elaidic acid
      offers considerable advantages since the method does not require use of a
      radioactive molecule, completely separates the two hydroxymetabolites, confirms
      the identification of each metabolite, and is as sensitive as the radiometric
      analysis method. This method allowed the comparative study of oleic and elaidic
      acid hydroxylations by both human and rat liver microsomal preparations.

PMID- 9766854
TI  - Quantitation of individual molecular species of phosphatidylcholines by reversed
      phase high-performance liquid chromatography with fluorometric detection.
AB  - The multiplicity of phosphatidylcholines is caused by the presence of different
      pairs of fatty acids in their individual molecular species and at least 27
      miscellaneous fatty acids were identified in phosphatidylcholines in the serum of
      healthy individuals by combined gas-liquid chromatography and mass spectrometry
      in our present experiments. A method is described for the separation and
      quantitation of molecular species of phosphatidylcholine in human serum. Total
      phosphatidylcholine is isolated from lipids extracted from the serum with
      chloroform-methanol (2:1) by reversed-phase liquid-liquid extraction and
      subjected to reversed-phase high-performance liquid chromatography with a
      discontinuous descending gradient of water. Separation is monitored by
      fluorometry (340/460 nm) and absorption at 205 nm, if required. Up to 25
      different molecular species of phosphatidylcholine may be quantified with a
      satisfactory reproducibility (+/-5-8%). Data on the distribution of individual
      molecular species in phosphatidylcholine of 53 normal serums are presented. The
      method may be used for quantitation of these phospholipids also in other
      biological materials (cell lines, leukemic cells from patients), and on a
      micropreparative scale to isolate individual compounds. The speed of separation
      as well as a satisfactory reproducibility are its principal advantages.

PMID- 9766851
TI  - Enantioselective multidimensional gas chromatography-mass spectrometry in the
      analysis of urinary organic acids.
AB  - Enantioselective multidimensional gas chromatography-mass spectrometry is a
      valuable tool for the enantioselective analysis of compounds from complex
      matrices. Samples are separated initially on a precolumn and selected substances
      then transferred on-line to a main-column coated with suitable chiral stationary
      phase for enantioselective analysis with subsequent mass selective detection. In
      this paper the method is used as an adjunct to urinary organic acid analysis to
      provide information in patients with suspected inborn errors of metabolism.
      Lactic acid, alpha-hydroxyisocaproic acid, 3-phenyllactic acid and 3-(4
      hydroxyphenyl)-lactic acid are separated in a single run. In addition, the
      enantioselective analysis of pyroglutamic acid is presented. D-Enantiomers of
      amino acids and alpha-hydroxycarboxylic acids derived from amino acids, point to
      a bacterial origin whereas the L-enantiomer is predominantly of endogenous
      origin. Therefore the enantiomeric ratio of chiral metabolites is an important
      parameter for the understanding of metabolic processes.

PMID- 9766855
TI  - Studies on neurosteroids. VII. Determination of pregnenolone and its 3-stearate
      in rat brains using high-performance liquid chromatography-atmospheric pressure
      chemical ionization mass spectrometry.
AB  - An assay method for pregnenolone and its 3-stearate in rat brains has been
      developed using LC-atmospheric pressure chemical ionization (APCI) isotope
      dilution MS. The extraction of the rat brain homogenate containing deuterated
      internal standards (ISs) with organic solvent followed by silica gel mini-column
      chromatography gave two fractions containing pregnenolone and its 3-stearate
      together with the respective IS. Each fraction was derivatized into 3-acetate-20
      methyloxime and 20-methyloxime, respectively, followed by silica gel mini-column
      chromatography to remove the excess reagents, and then each derivatized fraction
      was applied onto reversed-phase LC-APCI-MS. The method was applied to the
      determination of these steroids in the gray matter and olfactory bulbs of rat
      brains, which were divided into control and acute stressed specimens. Although
      pregnenolone in both regions of the rat brains increased more than five times
      after stress, its 3-stearate decreased after stress.

PMID- 9766856
TI  - Efficient bispecific monoclonal antibody purification using gradient thiophilic
      affinity chromatography.
AB  - Bispecific monoclonal antibodies (bsMAbs), due their unique design, have a wide
      range of potential applications in immunodiagnostics and immunotherapy. One of
      the major limitations for the use of bsMAbs produced by hybrid-hybridomas is the
      concomitant production of parental monospecific antibodies. The relative amount
      of bsMAb secreted may vary between different hybrid-hybridomas. Hence, the
      purification of the desired bispecific molecule from other forms is crucial.
      Current purification methods include anion-exchange, HPLC on different matrices,
      and dual affinity methods. Most of those methods include multiple steps and have
      limitations on the purity or yield of the desired species. We report here a
      simple single-step purification method, using inexpensive thiophilic
      chromatography. This new method can potentially be scaled up, for industrial
      proposes. Finally, based on the amino acid sequences and assembly of the two
      heavy chains we attempt to explain the possible mechanism by which thiophilic
      chromatography was able to resolve the bsMAbs from the monospecific species.

PMID- 9766857
TI  - Drug accumulation in melanin: an affinity chromatographic study.
AB  - The affinity of several drugs to melanin has been indirectly assessed using an
      affinity chromatographic approach based on immobilized melanin. Plots of the
      retention of the drugs on the affinity column versus the number of molecules
      applied were fitted best by nonlinear, exponential curves characteristic for each
      drug. These curves reflect the complexity of the binding behaviour, consisting of
      a variety of hydrogen bonding, hydrophobic or ionic interactions as well as
      cooperative or anti-cooperative interactions between the drug molecules and
      melanin. The nonlinear fitting procedure was based on a descriptive function and
      allowed to discriminate the binding behaviour according to parameter estimates
      which specified the investigated drugs.

PMID- 9766858
TI  - Detection of 4-hydroxycoumarin anticoagulants and their metabolites in urine as
      part of a systematic toxicological analysis procedure for acidic drugs and
      poisons by gas chromatography-mass spectrometry after extractive methylation.
AB  - A gas chromatography-mass spectrometry (GC-MS) procedure was developed for the
      detection of 4-hydroxycoumarin anticoagulants and their metabolites in urine as
      part of a systematic toxicological analysis procedure for acidic drugs and
      poisons after extractive methylation. The part of the phase-transfer catalyst
      remaining in the organic phase was removed by solid-phase extraction on a diol
      phase. The compounds were separated by capillary GC and identified by
      computerized MS in the full scan mode. Using mass chromatography with the ions
      m/z 291, 294, 295, 309, 313, 322, 324, 336, 343 and 354, the possible presence of
      4-hydroxycoumarin anticoagulants and/or their metabolites could be indicated. The
      identity of positive signals in such mass chromatograms was confirmed by
      comparison of the peaks underlying full mass spectra with the reference spectra
      recorded during this study. This method allowed the detection of therapeutic
      concentrations of phenprocoumon and warfarin in human urine samples. In absence
      of human urine, acenocoumarol, coumachlor, coumatetrayl, pyranocoumarin
      (cyclocumarol) could be detected only in rat urine.

PMID- 9766859
TI  - Report on the preparation of deuterium-labelled aconitine and mesaconitine and
      their application to the analysis of these alkaloids from body fluids as internal
      standard.
AB  - Improved analysis of aconitine and mesaconitine, highly toxic compounds from
      Aconitum species, in body fluids by gas chromatography-selected ion monitoring
      with their deuterium-labelled analogues as internal standards (I.S.s) is
      described. Deuterium-labelled analogues of aconitine and mesaconitine were
      synthesized by the substitution of the N-alkyl group for a deuterium-labelled
      one. The mass spectra of the derivatives of the deuterium labels closely
      resembled that of the nonlabelled compounds except for an obvious mass shift
      produced by substitution of the deuterium atoms at N-alkyl groups. Using these
      deuterium-labelled compounds as I.S.s, the standard curves for aconitine and
      mesaconitine were linear (r2=0.999 each) in the concentration range of 50 pg to
      50 ng, respectively. The detection limit of the alkaloids was 10 pg each per
      injection. The recovery, accuracy and precision of the analysis were evaluated
      with three different concentration of spiked human blood and urine (n=5 each).
      The recovery rates ranged from 97.6% to 101.3% and the standard deviations of the
      interseries ranged from 2.1% to 3.9%. These I.S.s give us a more precise analysis
      and may be useful in examining the behavior of these alkaloids in the human body.

PMID- 9766860
TI  - Headspace solid-phase microextraction and gas chromatographic determination of
      dinitroaniline herbicides in human blood, urine and environmental water.
AB  - Solid-phase microextraction (SPME) is a unique extraction and sampling technique,
      and it has been used for separation of volatile organics from water or other
      simple matrices. In this study, we have used SPME to separate dinitroaniline
      herbicides from complicated matrices of human urine and blood in order to broaden
      its application to biomedical analysis. The SPME conditions were optimized for
      water, urine and blood samples, in terms of pH, salt additives, extraction
      temperature, and fiber exposure time. Urine or water (1.0 ml) spiked with
      herbicides and 0.28 g of anhydrous sodium sulfate was preheated at 70 degrees C
      for 10 min, and a polydimethylsiloxane-coated fiber for SPME was exposed to the
      headspace at 70 degrees C for another 30 min; while spiked blood (0.5 ml) diluted
      with water (0.5 ml) was treated at 90 degrees C in the same way. The herbicides
      were extractable under these conditions, and could be determined by gas
      chromatography-electron capture detector (GC-ECD). The recoveries of the
      herbicides, measured at the concentrations of 0.50 and 1.0 ng/ml urine or water,
      or 6.0 and 20 ng/0.5 ml blood, ranged from 35 to 64% for different herbicides
      from water or urine, and from 3.2 to 7.2% from blood. The headspace SPME yielded
      clean extracts of dinitroaniline herbicides from urine, blood or water, which
      could be directly analyzed by GC-ECD without further purification. The peak areas
      of the extracted herbicides were proportional to their concentrations in the
      range 0.1-10 ng/ml in water or urine, or 1-60 ng/0.5 ml in blood. The lowest
      detectable concentration of the herbicides lay in 0.1 ng/ml water or urine, or in
      0.5 ng/0.5 ml blood. The intra- and inter-day coefficients of variation were
      within 14% for most of the analytes. Although the recoveries of the herbicides
      were rather low, the linearity of calibration curve and the precision were good.
      The developed method is more sensitive and much simpler in sample preparation
      than previously reported ones. With the established SPME method, a dosed
      herbicide was successfully separated and determined in rats' blood.

PMID- 9766861
TI  - Determination of Aconitum alkaloids in blood and urine samples. II. Capillary
      liquid chromatographic-frit fast atom bombardment mass spectrometric analysis.
AB  - Determination of fourteen alkaloids, toxic Aconitum alkaloids, aconitine,
      mesaconitine, jesaconitine, hypaconitine and deoxyaconitine, and their hydrolysis
      products, benzoylaconines and aconines, have been established using capillary
      liquid chromatography (LC) fast atom bombardment mass spectrometry (FAB-MS) with
      a frit interface. Protonated molecular ions were observed as base peaks in the
      FAB-MS for these fourteen alkaloids. All the alkaloids were simultaneously
      quantified with linear gradient LC elution by solvent mixture of acetonitrile and
      0.3% trifluoroacetic acid using selected ion monitoring of the protonated
      molecular ions. The calibration curves of these alkaloids were linear in
      injection amounts ranging from 5 to 500 pg, and their detection limits were 1 pg
      per injection (S/N=3). Solid-phase extraction using Sep-Pak Plus PS-1 was also
      investigated to clean-up and concentrate alkaloids in blood and urine samples,
      and showed satisfactory recoveries. This capillary LC-frit-FAB-MS method enables
      determination of low levels of Aconitum alkaloids in blood and urine samples,
      coupled with solid-phase extraction.

PMID- 9766862
TI  - Three-step purification of lipopolysaccharide-free, polyhistidine-tagged
      recombinant antigens of Mycobacterium tuberculosis.
AB  - Previous work has shown that the study of host immune responses against
      Mycobacterium tuberculosis, the causative agent of tuberculosis, requires the
      availability of multiple mycobacterial antigens. Since purification of protein
      from M. tuberculosis cells is extremely cumbersome, we developed a protocol for
      purifying milligram amounts of ten recombinant antigens of M. tuberculosis from
      E. coli cells. Purified proteins were immunologically active and free of
      contaminants that confound interpretation of cell-based immunological assays. The
      method utilizes a three-step purification protocol consisting of immobilized
      metal-chelate affinity chromatography, size exclusion chromatography and anion
      exchange chromatography. The first two chromatographic steps yielded recombinant
      protein free of protein contaminants, while the third step (anion-exchange
      chromatography) efficiently removed E. coli lipopolysaccharide, a potent
      polyclonal activator of lymphoid cells. The recombinant proteins were
      immunologically indistinguishable from their native (i.e., purified from M.
      tuberculosis) counterparts. Thus the method provides a way to utilize recombinant
      proteins for immunological analyses that require highly purified antigens.

PMID- 9766863
TI  - Determination of morphine by high-performance liquid chromatography with
      electrochemical detection: application to human and rabbit pharmacokinetic
      studies.
AB  - A rapid, sensitive, precise and accurate high-performance liquid chromatographic
      assay with coulometric electrochemical detection was developed for the
      determination of morphine in human, rabbit, pig and dog plasma. It includes a one
      step extraction procedure with hexane-isoamyl alcohol (1:1, v/v) at pH 8.9
      (adjusted with phosphoric acid) and reversed-phase liquid chromatography on a
      microPorasil column. The mobile phase was composed of 5 mM sodium acetate buffer
      (pH 3.75)-acetonitrile (25:75, v/v). A flow-rate of 1.2 ml/min at 20 degrees C
      was used. The working potentials for the electrochemical detector were +0.20 V
      for detector cell 1, +0.55 V for detector cell 2 and +0.75 V for the guard cell.
      The limit of detection of morphine was 100 pg/ml of plasma. Repeatability,
      precision and accuracy were also determined concomitantly. The calibration graphs
      were linear in the concentration range 0.25-250 ng/ml with correlation
      coefficients of 0.998+/-0.01 and with a minimum intercept of 0.05+/-0.08. The
      precision in plasma was acceptable, with coefficients of variation less than 11%.
      The absolute recoveries of morphine and nalbuphine (internal standard) were
      between 86 and 89% and independent of morphine concentration. Pharmacokinetics
      after oral morphine [MST Continus (morphine sulphate tablets) 30 mg, Bard
      Pharmaceutical, Cambridge, UK] in humans revealed a one-compartment first-order
      absorption model with one absorption phase and one elimination phase. The
      absorption and elimination half-lives were 2.46 and 1.80 h, respectively.
      Pharmacokinetics after intravenous morphine (3 mg/kg) in rabbits showed a linear
      two-compartment open model with one distribution phase and one elimination phase.
      The distribution and elimination half-lives were 0.5 and 33.8 h, respectively.

PMID- 9766864
TI  - Role of stationary phase and eluent composition on the determination of log P
      values of N-hydroxyethylamide of aryloxyalkylen and pyridine carboxylic acids by
      reversed-phase high-performance liquid chromatography.
AB  - The partition coefficients, P, between n-octanol and water of a number of growth
      stimulating substances, N-hydroxyethylamide of aryloxyalkylen- and pyridine
      carboxylic acids were obtained from Pomona College (C log P), and Rekker's (log
      P(Rekker)) revised fragmental constant system was used to calculate log P data
      sets. Both of these data sets were correlated with two different substance
      lipophilicity parameters, log k(w) and phi0. Log k(w) was obtained by
      extrapolation of log retention factor (k) to 0% organic modifier measured in
      reversed-phase liquid chromatography (RPLC) systems. Phi0 values were obtained
      from the slopes and intercepts of these relationships. The RPLC experiments were
      performed on four commercially available reversed-phase columns. Binary mixtures
      of methanol-water, methanol-phosphate buffer (pH 7.0), methanoltricine buffer (pH
      7.0) and acetonitrile-water were used as mobile phases for the determination of
      log k(w) values. For the methanolic eluents linear regression provided
      satisfactory correlations (r>0.99) for the relationships log k vs. organic
      modifier content in the eluent, while for the acetonitrile-containing eluents a
      second-degree polynominal regression was necessary. For all four RPLC columns, by
      linear regression satisfactory correlations (r>0.99) were obtained between log
      k(w) and log P data using methanolic eluents. In such eluents phi0 values were
      shown to be the second-best lipophilicity parameters. For acetonitrile-containing
      eluents the use of second-degree polynominal regression was necessary and, in
      contrast to methanol, significant influence of the applied column on regression
      results was observed. For acetonitrile-containing eluents the phi0-index does not
      provide satisfactory results for our substances. No difference in regression
      results between the use of buffered and non-buffered eluents was observed.

PMID- 9766865
TI  - Determination of medrogestone in plasma by high-performance liquid
      chromatography.
AB  - Interference with the UV absorbance of medrogestone by endogenous steroids in
      plasma was prevented by reacting plasma with oxalyl chloride. The reduction of
      interference was effective when oxalyl chloride was in the range 10-50 microl/ml
      plasma. Reaction of oxalyl chloride with plasma for 10 min could reduce
      interference approximately 5.5-fold, and there was no significant reduction after
      30 min. The limit of quantitative concentration for medrogestone in HPLC was 1
      ng/ml. The standard curves were linear with the correlation coefficient greater
      than 0.999 in the range of 1-30 ng/ml. The coefficients of variation of both
      intra- and inter-day mean values were <12% and <10% of the actual values,
      respectively. The developed method for plasma sample preparation and the
      evaluated HPLC condition were further applied to an in vivo pharmacokinetic
      study.

PMID- 9766866
TI  - Quantification of penicillin-G and procaine in equine urine and plasma using high
      performance liquid chromatography.
AB  - A rapid and sensitive method for the extraction and quantification of penicillin
      G and procaine in horse urine and plasma samples has been successfully developed.
      The method involves the use of solid-phase extraction (SPE) for penicillin-G,
      liquid-liquid extraction (LLE) for procaine, and high-performance liquid
      chromatography (HPLC) for the quantification of penicillin-G and procaine. The
      new method described here has been successfully applied in the pharmacokinetic
      studies of procaine, penicillin-G and procaine-penicillin-G administrations in
      the horse.

PMID- 9766867
TI  - Stereoselective binding of ketoprofen enantiomers to human serum albumin studied
      by high-performance liquid affinity chromatography.
AB  - A chiral stationary phase based on immobilized human serum albumin (HSA) was used
      to study the stereoselective binding of ketoprofen enantiomers by means of high
      performance liquid affinity chromatography. The technique of zonal elution was
      applied together with a novel mathematical approach describing attachment to more
      than one type of binding site. Phenylbutazon (PBZ) and diazepam (DAZ) were used
      as markers for the major believed binding regions on HSA. Both R- and S
      ketoprofen (KTR and KTS) display high affinity to the primary PBZ- and DAZ
      binding sites and low-affinity to the secondary DAZ sites. The binding to high
      affinity regions is accepted to be a stepwise process initiated by the binding to
      the primary DAZ sites and followed by the attachment to the primary PBZ sites.
      The chiral recognition is attributed to the high-affinity PBZ-binding sites and
      to the low-affinity DAZ-binding sites.

PMID- 9766868
TI  - Quantitative determination of the angiotensin-converting enzyme inhibitor
      cilazapril and its active metabolite cilazaprilat in pharmaceuticals and urine by
      high-performance liquid chromatography with amperometric detection.
AB  - A rapid and simple high-performance liquid chromatographic method with
      amperometric detection has been developed for the quantitation of cilazapril and
      its active metabolite and degradation product cilazaprilat in urine and tablets.
      The chromatographic system consisted of a microBondapak C18 column, using a
      mixture of methanol-5 mM phosphoric acid (50:50, v/v) as mobile phase, which was
      pumped at a flow-rate of 1.0 ml/min. The column was kept at a constant
      temperature of (40+/-0.2) degrees C. Detection was performed using a glassy
      carbon electrode at a potential of 1350 mV. Sample preparation for urine
      consisted of a solid-phase extraction using C8 cartridges. This procedure allowed
      recoveries greater than 85% for both compounds. The method proved to be accurate,
      precise and sensitive enough to be applied to pharmacokinetic studies and it has
      been applied to urine samples obtained from four hypertensive patients (detection
      limit of 50 ng/ml for cilazapril and 40 ng/ml for cilazaprilat in urine). Results
      were in good agreement with pharmacokinetic data.

PMID- 9766869
TI  - High-performance liquid chromatographic determination of nemonapride and
      desmethylnemonapride in human plasma using an electrochemical detection.
AB  - A high-performance liquid chromatographic method using an electrochemical
      detector (HPLC-ED) was developed for the determination of nemonapride and its
      active metabolite, desmethylnemonapride in human plasma. Nemonapride,
      desmethylnemonapride and moperone chloride, which was used as the internal
      standard (I.S.) in plasma, were extracted by a rapid and simple procedure based
      on C18 bonded-phase extraction, and were separated by C8 reversed-phase HPLC
      column. Nemonapride and desmethylnemonapride were detected by high conversion
      efficiency amperometric detection at +0.84 V. Determination of both nemonapride
      and desmethylnemonapride were possible in the concentration range at 0.25-5.0
      ng/ml, and the limit of detection for each was 0.1 ng/ml. The recoveries of
      nemonapride and desmethylnemonapride added to plasma were 97.0-98.2% and 96.7
      98.8%, respectively, with coefficients of variation of less than 7.2% and 10.3%,
      respectively. This method is applicable to drug level monitoring in the plasma of
      schizophrenia patients treated with nemonapride and to the study of
      pharmacokinetics.

PMID- 9766871
TI  - Determination of olanzapine in serum by high-performance liquid chromatography
      using ultraviolet detection considering the easy oxidability of the compound and
      the presence of other psychotropic drugs.
AB  - A method for determination of the atypical neuroleptic drug olanzapine in serum
      was developed. After a single-step liquid-liquid extraction, the compound was
      separated from other constituents on a normal-phase silica gel column using a
      buffer-methanol mobile phase and measured by UV absorption at 270 nm. Addition of
      0.25% ascorbic acid to serum protects olanzapine against oxidation during
      extraction and stabilizes the easily oxidised compound during storage. Inter-day
      variation was <8% at serum levels found in olanzapine treated patients.
      Analytical interference from coadministered psychoactive drugs and their
      metabolites were studied. Only risperidone, also a relatively newly developed
      antipsychotic drug, interfered, but the most commonly used antidepressants and
      traditional antipsychotics and their metabolites did not interfere.

PMID- 9766870
TI  - Determination of clozapine, desmethylclozapine and clozapine N-oxide in human
      plasma by reversed-phase high-performance liquid chromatography with ultraviolet
      detection.
AB  - An isocratic high-performance liquid chromatography (HPLC) method with
      ultraviolet detection for the simultaneous determination of clozapine and its two
      major metabolites in human plasma is described. Analytes are concentrated from
      alkaline plasma by liquid-liquid extraction with n-hexane-isoamyl alcohol (75:25,
      v/v). The organic phase is back-extracted with 150 microl of 0.1 M dibasic
      phosphate (pH 2.2 with 25% H3PO4). Triprolidine is used as internal standard. For
      the chromatographic separation the mobile phase consisted of acetonitrile-0.06 M
      phosphate buffer, pH 2.7 with 25% phosphoric acid (48:52, v/v). Analytes are
      eluted at a flow-rate of 1.0 ml/min, separated on a 250 x 4.60 mm I.D. analytical
      column packed with 5 microm C6 silica particles, and measured by UV absorbance
      detection at 254 nm. The separation requires 7 min. Calibration curves for the
      three analytes are linear within the clinical concentration range. Mean
      recoveries were 92.7% for clozapine, 82.0% for desmethylclozapine and 70.4% for
      clozapine N-oxide. C.V. values for intra- and inter-day variabilities were < or =
      13.8% at concentrations between 50 and 1000 ng/ml. Accuracy, expressed as
      percentage error, ranged from -19.8 to 2.8%. The method was specific and
      sensitive with quantitation limits of 2 ng/ml for both clozapine and
      desmethylclozapine and 5 ng/ml for clozapine N-oxide. Among various psychotropic
      drugs and their metabolites, only 2-hydroxydesipramine caused significant
      interference. The method is applicable to pharmacokinetic studies and therapeutic
      drug monitoring.

PMID- 9766872
TI  - Fully automated high-performance liquid chromatography of ciprofloxacin with
      direct injection of plasma and Mueller-Hinton broth for
      pharmacokinetic/pharmacodynamic studies.
AB  - An isocratic high-performance liquid chromatographic method with column switching
      and direct injection has been developed to determine ciprofloxacin in plasma and
      Mueller-Hinton broth. An on-line dilution of the sample was performed with a
      loading mobile phase consisting of 173 mM phosphoric acid. The analyte was
      retained on a LiChrocart 4-4 precolumn filled with a LiChrospher 100 RP18, 5
      microm. An electric-actuated system with two six-port valves allowed a clean-up
      step with a mixture 20 mM phosphate buffer (pH 3.5)-methanol (97:3, v/v) and the
      transfer of the analyte by a back-flush mode to a 150 x 4.6 mm I.D. column packed
      with a Kromasil C8 5 microm, using a mobile phase of 20 mM phosphate buffer (pH
      3.5)-acetonitrile (85:15, v/v). Fluorescence detection allowed a quantification
      limit of 0.078 microg/ml with a 40-microl sample size. The method was evaluated
      to determine its usefulness in studying the pharmacokinetic/pharmacodynamic
      behaviour of ciprofloxacin in an in vitro model.

PMID- 9766873
TI  - Characterization of a Helicobacter pylori vaccine candidate by proteome
      techniques.
AB  - In a previous two-dimensional (2D) gel electrophoretic study of protein antigens
      of the gastric pathogen, Helicobacter pylori recognized by human sera, one of the
      highly and consistently reactive antigens, a protein with Mr of approximately
      30,000 (Spot 15) seemed to be of special interest because of low yields on N
      terminal protein sequencing. This suggested possible N-terminal modification, as
      the N-terminal sequence analysis of this 30,000 protein (Spot 15) did not provide
      a definitive match within the H. pylori genomic database. This protein was
      isolated by 2D polyacrylamide gel electrophoresis, evaluated by liquid
      chromatography-mass spectrometry, and found to consist of two related species of
      approximately 28,100 and 26,500. In parallel, the proteins within this spot were
      digested in situ with the endoprotease Lys-C. Analysis of the Lys-C digest by
      matrix-assisted laser desorption time-of-flight mass spectrometry, peptide
      mapping, and sequence analysis was conducted. Comparison of the mass and sequence
      of the Lys-C peptides with those derived from a H. pylori genomic library
      identified an open reading frame of approximately 300 base pairs as the source of
      the Spot 15 protein. This corresponded to HP0175 in the recently reported H.
      pylori genome sequence, an open reading frame with some homology to Campylobacter
      jejeuni cell binding protein 2. Mass spectral and sequence analysis indicated
      that Spot 15 was a processed product generated by proteolytic cleavage at both
      the carboxy and amino termini of the 34 open reading frame precursor.

PMID- 9766874
TI  - Determination of 2-n-propylquinoline in mouse plasma and liver by high
      performance liquid chromatography.
AB  - A high-performance liquid chromatographic method was developed for the specific
      determination of 2-n-propylquinoline, a new anti-leishmaniasis drug, in plasma
      and liver homogenates of mice. 2-n-Propylquinoline was extracted with methyl
      tert.-butyl ether with quinoline as internal standard. Separation was carried out
      using a Nucleosil C18 column. The mobile phase consisted of methanol-0.005 M
      ammonium acetate buffer (60:40) at pH 5.5 and 8 for plasma and liver homogenates,
      respectively. Detection was monitored at 233 nm. The method was validated and
      shown to be accurate and precise for plasma and liver homogenates. Extraction
      yield was 96% in plasma and 81% in liver homogenates. This method was used to
      determine the pharmacokinetic profile of 2-n-propylquinoline following oral
      administration to mice.

PMID- 9766875
TI  - Assay for the quinocarmycin analog DX-52-1 in human plasma using high-performance
      liquid chromatography with automated column switching and low wavelength
      ultraviolet detection.
AB  - The hydrocyanated derivative of the antitumor antibiotic quinocarmycin, DX-52-1
      (I), exhibits impressive activity against human melanoma xenograft models in
      vivo. Phase I clinical trials to evaluate this compound as an antineoplastic
      agent have been initiated by the US National Cancer Institute. We have developed
      an HPLC assay for the determination of I in human plasma involving automated
      column switching and UV detection at 210 nm. The preparation of samples for
      chromatographic analysis entails the preliminary removal of plasma proteins by
      precipitation with acetonitrile, acidifying the clear supernatant to pH 4.5, then
      extracting twice with tert.-butyl methyl ether to recover the drug. A heart
      cutting procedure employing two HPLC columns with contrasting retention
      characteristics under isocratic reversed-phase conditions was used to achieve the
      selectivity required for low wavelength UV detection of the analyte. The sample
      extract was initially loaded onto a column packed with a cyanopropyl stationary
      phase. During the predetermined time interval that I eluted from this column, a
      fully automated six-position switching valve was used to direct the effluent onto
      an octadecylsilane analytical column. The assay has been thoroughly validated
      with regard to linearity, inter- and intra-day accuracy and precision, recovery,
      selectivity and specificity. Using a sample volume of 1.0 ml, the lowest
      concentration of I quantified with acceptable day-to-day reproducibility was
      found to be 2.56 ng/ml (R.S.D. 18.9%, n=21, 4 months). This proved to be
      sufficiently sensitive for pharmacokinetic drug level monitoring in cancer
      patients treated with a 6-h continuous intravenous infusion of I, even at the
      starting dose of 3 mg/m2. The successful performance and reliability of the assay
      has been demonstrated through extensive application to the routine analysis of
      plasma specimens acquired during a phase I clinical trial of the drug.

PMID- 9766876
TI  - Trace analysis of SN-38 in human plasma by high-performance liquid
      chromatography.
AB  - A reversed-phase high-performance liquid chromatographic method with fluorescence
      detection was developed and validated for the quantitation of SN-38, the active
      metabolite of irinotecan (CPT-11), a new anticancer drug. This method uses solid
      phase extraction with a C18 column for sample clean-up and concentration
      following acidification of human plasma with two volumes of 0.1 M HCl. Using
      blank plasma spiked with SN-38, we found the assay to be linear over the
      concentration range of 10-500 pM (3.9-195 pg/ml) with acceptable total and within
      day imprecision. The recovery of SN-38 ranged from 48.3% (10 pM) to 91.5% (500
      pM) whereas that of the internal standard, 20-(S)-camptothecin, was 96.9% (500
      pM). This method represents a sizeable increase in sensitivity over other
      published methods and is shown to be suitable for the measurement of 'trough'
      concentrations of SN-38 during the treatment of patients with a weekly regimen of
      irinotecan.

PMID- 9766877
TI  - High-throughput solid-phase extraction for the determination of cimetidine in
      human plasma.
AB  - For the implementation and validation of an automated 'high-throughput' solid
      phase extraction (SPE) system, using microtiter solid-phase technology and a
      pipetting robot, a SPE method previously validated manually for cimetidine in
      human plasma was adapted. Sample cleanup was performed by means of SPE using
      Microlute extraction plates in the 96-well format, each well filled with 50 mg of
      Varian C18 sorbent. Separation was performed by reversed-phase high-performance
      liquid chromatography (HPLC) with UV detection at 234 nm. The validated
      calibration range was from 0.100 to 5.00 mg/l, with an inaccuracy and imprecision
      below 20% at all concentration levels. Validation results on linearity,
      specificity, precision, accuracy and stability are shown and are found to be
      adequate. Cross-check analysis of samples from a clinical trial showed that there
      is a good correlation between results obtained by the automated method and
      results obtained by the manual method. The average sample preparation time for a
      technician decreased from approximately 4 min per sample to 0.6 min. A sample
      throughput of at least 160 samples per day can be achieved, the HPLC analysis
      time being the rate-limiting step.

PMID- 9766878
TI  - Determination of naringenin and its glucuronide conjugate in rat plasma and brain
      tissue by high-performance liquid chromatography.
AB  - An isocratic high-performance liquid chromatographic method with ultraviolet
      detection was utilized for the investigation of the pharmacokinetics of
      naringenin and its glucuronide conjugate in rat plasma and brain tissue. Plasma
      and brain tissue were deproteinized by acetonitrile, then centrifuged for sample
      clean-up. The drugs were separated by a reversed-phase C18 column with a mobile
      phase consisting of acetonitrile-orthophosphoric acid solution (pH 2.5-2.8)
      (36:64, v/v). The detection limits of naringenin in rat plasma and brain tissue
      were 50 ng/ml and 0.4 microg/g, respectively. The glucuronide conjugate of
      naringenin was evaluated by the deconjugated enzyme beta-glucuronidase. The
      naringenin conjugation ratios in rat plasma and brain tissue were 0.86 and 0.22,
      respectively, 10 min after naringenin (20 mg/kg, i.v.) administration. The mean
      naringenin conjugation ratio in plasma was approximately four fold that in brain
      tissue.

PMID- 9766879
TI  - Liquid chromatographic determination of myocardial interstitial epinephrine.
AB  - This study describes a high-performance liquid chromatographic method with
      electrochemical detection (HPLC-ED) for monitoring of epinephrine (Epi) in the
      myocardial interstitial space. The in vitro detection limit for Epi was 200 fg in
      a 50-microl injection. Using a cardiac dialysis technique, 60-microl dialysates
      were sampled from the myocardial interstitial space (6-min fractions). After an
      alumina procedure, the dialysate Epi concentration was measured using the HPLC-ED
      system. Although the basal Epi concentration was undetectable, local
      administration of desipramine increased Epi concentration of the dialysate to
      38.1+/-18.5 pg/ml. This system affords a new possibility for estimating
      myocardial interstitial Epi level.

PMID- 9766880
TI  - High-performance liquid chromatographic determination of a new oral thrombin
      inhibitor in the blood of rats and dogs.
AB  - A reliable reversed-phase high-performance liquid chromatographic method has been
      developed for the determination of a new oral thrombin inhibitor (compound I) in
      the blood of rats and dogs. The analyte was deproteinized with a 1.5 volume of
      methanol and a 0.5 volume of 10% zinc sulfate, and the supernatant was injected
      into a 5-microm Capcell Pak C18 column (150 x 4.6 mm I.D.). The mobile phase was
      a mixture of acetonitrile and 0.2% triethylamine of pH 2.3 (31:69, v/v) with a
      flow-rate of 1.0 ml/min at UV 231 nm. The retention time of compound I was
      approximately 9.3 min. The calibration curve was linear over the concentration
      range of 0.05-100 mg/l for rat blood (r2>0.9995, n=6) and dog blood (r2>0.9993,
      n=6). The limit of quantitation was 0.05 mg/l for both bloods using a 100-microl
      sample. For the 5 concentrations (0.05, 0.1, 1, 10, and 100 mg/l), the within-day
      recovery (n=4) and precision (n=4) were 98.1-104.1% and 1.5-6.8% for rat blood
      and 95.4-105.7% and 1.4-5.3% for dog blood, respectively. The between-day
      recovery (n=6) and precision (n=6) were 99.8-105.3% and 3.7-12.6% for rat blood
      and 87.5-107.1% and 2.9-15.3% for dog blood, respectively. The absolute
      recoveries were 82.4-93.3%. No interferences from endogenous substances were
      observed. In conclusion, the presented simple, sensitive, and reproducible HPLC
      method proved and was used successfully for the determination of compound I in
      the preclinical pharmacokinetics.

PMID- 9766881
TI  - Simultaneous determination of ritonavir and saquinavir, two human
      immunodeficiency virus protease inhibitors, in human serum by high-performance
      liquid chromatography.
AB  - The aim of this study was to describe an high-performance liquid chromatographic
      assay for the simultaneous determination of two HIV protease inhibitors,
      saquinavir and ritonavir, in human serum. The method involved extraction of
      ritonavir and saquinavir from serum with the aid of solid-phase extraction C18
      cartridges followed by high-performance liquid chromatography with a C8 column
      and ultraviolet detection set at a wavelength of 240 nm. The assay was linear and
      has been validated over the concentrations range of 0.5-32 microg/ml for
      ritonavir and 0.075-4.8 microg/ml for saquinavir, from 600 microl serum
      extracted. In future, the assay will be used to support human population
      pharmacokinetic studies, and therapeutic drug monitoring for ritonavir and
      saquinavir.

PMID- 9766882
TI  - Sulfalene concentrations in plasma and blood cells of Plasmodium falciparum
      malaria cases after treatment with metakelfin using high-performance liquid
      chromatography.
AB  - A reversed-phase high-performance liquid chromatographic method using
      acetonitrile-methanol-1 M perchloric acid-water (25:9:0.8:95, v/v/v) at a flow
      rate of 1.0 ml min(-1) on LiChrospher 100 RP 18 column (250 x 4 mm; 5 microm)
      with UV (254 nm) detection has been developed for the determination of sulfalene
      in plasma and blood cells after oral administration of the antimalarial drug
      metakelfin. Calibration curves were linear in the range 0.5-100 microg ml(-1).
      The limit of quantification was 50 ng ml(-1). Within-day and day-to-day
      coefficients of variation averaged 3.84 and 5.31%, respectively. Mean extraction
      recoveries of sulfalene from plasma and blood cells were 87.21 and 84.65%,
      respectively. Mean concentrations of sulfalene in plasma of P. falciparum cases
      on days 2, 7 and 15 were 44.58, 14.90 and 1.70 microg ml(-1), respectively; in
      blood cells concentrations of sulfalene were 7.77, 3.25 and 0.75 microg ml(-1),
      respectively, after oral treatment with two tablets (1000 mg) of metakelfin.
      Significant difference was recorded on day 2 for sulfalene concentration in blood
      cells of healthy and P. falciparum cases (t=9.49; P<0.001).

PMID- 9766883
TI  - Determination of cisapride and norcisapride in human plasma using high
      performance liquid chromatography with ultraviolet detection.
AB  - A simple, rapid and reproducible high-performance liquid chromatographic assay
      for cisapride and norcisapride in human plasma is described. Samples of plasma
      (150 microl) were extracted using a C18 solid-phase cartridge. Regenerated tubes
      were eluted with 1.0 ml of methanol, dried, redissolved in 150 microl of methanol
      and injected. Chromatography was performed at room temperature by pumping
      acetonitrile-methanol-0.015 M phosphate buffer pH 2.2-2.3 (680:194:126, v/v/v) at
      0.8 ml/min through a C18 reversed-phase column. Cisapride, norcisapride and
      internal standard were detected by absorbance at 276 nm and were eluted at 4.3,
      5.3 and 8.1 min, respectively. Calibration plots in plasma were linear (r>0.998)
      from 10 to 150 ng/ml. Intraday precisions for cisapride and norcisapride were
      3.3% and 5.4%, respectively. Interday precisions for cisapride and norcisapride
      were 9.6% and 9.0%, respectively. Drugs used which might be coadministered were
      tested for interference.

PMID- 9766884
TI  - Propagation and characterization of human herpesvirus-7 (HHV-7) isolates in a
      continuous T-lymphoblastoid cell line (SupT1).
AB  - After initial culture of HHV-7 in PHA-stimulated human cord blood mononuclear
      cells (HCBMC), six HHV-7 isolates were propagated successfully in an immature
      continuous T-lymphoblastoid cell line SupT1. All six isolates infected
      efficiently the SupT1 cells, and the infected cells became grossly enlarged and
      multinucleated 7-21 days post-infection. Various stages of HHV-7 morphogenesis
      were detected. Cell-free supernatants from HHV-7-infected SupT1 cells were
      infectious to HCBMC as well as to SupT1 cells. The HHV-7-infected SupT1 and HCBMC
      cell lysates contained more infectious virus than the centrifuged cell culture
      fluid supernates from the same culture. The HHV-7 isolates H7-2, H7-3, JHC, and
      JB, concentrated 500 times, had average infectivity titers of 10(3.0) TCID50/ml
      while strains H7-4 and KHR titered approximately 1-2 logs higher. When all six
      HHV-7 isolates were propagated in SupT1 and culture fluid supernatants were
      examined 14-21 days post-infection by negative stain electron microscopy they
      contained an average of 1.9 x 10(9) virus particles/liter. IFA and ELISA, using
      HHV-7/SupT1 cell lysate as an antigen, seem to correlate well in detecting high
      and low HHV-7 antibody in sera from chronic fatigue patients and healthy donors
      as controls. HHV-7 from SupT1 cell culture was free of HHV-6 and other human
      herpesviruses as tested by PCR, and the HHV-7 PCR signal was still strong when
      the viral preparation was diluted to 4.82 x 10(2) genome copies. Since HCBMC are
      expensive to obtain and available in only small amounts, it is difficult to
      obtain large quantities of HHV-7 antigen. On the other hand, the SupT1 cell is an
      excellent source to produce consistently sufficient quantities of HHV-7 for
      purification studies, development of immunodiagnostics, in vivo infectivity
      studies, evaluation of antiviral drugs, and molecular biological studies.

PMID- 9766885
TI  - Development of a dot blot neutralizing assay for HHV-6 and HHV-7 using specific
      monoclonal antibodies.
AB  - To elucidate further immune responses to human herpesviruses 6 and 7 (HHV-6 and 
      7), a neutralizing antibody assay was established for these viruses using a dot
      blot method. Three monoclonal antibodies against HHV-6 and 12 monoclonal
      antibodies against HHV-7 were developed and characterized by radio
      immunoprecipitation. One monoclonal antibody which recognizes the 135 kDa late
      polypeptide of HHV-6 and several which recognize the 125 kDa late polypeptide of
      HHV-7 were selected to monitor virus growth by a dot blot antigen-detection
      method. The dot blot method was then used for the assay of HHV-6 and -7
      neutralizing antibodies in human serum samples. The neutralization endpoints
      determined by the dot blot were comparable to those determined by
      immunofluorescence (IF). The neutralizing antibody titers appeared to correlate
      with the antibody titers determined by the indirect IF antibody test. The dot
      blot neutralization assay is easy to perform, is highly reproducible and
      objective when compared with the conventional methods based on cytopathology or
      IF for determining neutralization endpoints.

PMID- 9766886
TI  - Isolation of a retrovirus from multiple sclerosis patients in self-generated
      Iodixanol gradients.
AB  - The use of Iodixanol, a relatively new iodinated gradient medium, is described
      for isolation of a retrovirus, which was harvested from the supernatant of
      lymphoid cell lines originating from patients with multiple sclerosis (MS). The
      virus is produced in low amounts and has been shown to be fragile, as manifested
      in a loss of surface glycoproteins when purified in other gradient media. The
      gradient fractions were analysed after centrifugation in Iodixanol by
      incorporation of 3H-UTP, reverse transcriptase (RT) assays and electron
      microscopy (EM) and it was found that Iodixanol does not cause the degree of
      damage to the particles observed previously. These more favourable conditions are
      probably due to low viscosity and almost iso-osmotic conditions even in high
      concentrations. Furthermore, these advantages go together with higher
      reproducibility in self-forming gradients, easier handling and shorter
      centrifugation time. Iodixanol can also be used for preparation of HTLV-1.

PMID- 9766887
TI  - Flow cytometric detection of EBV (EBER snRNA) using peptide nucleic acid probes.
AB  - The application of peptide nucleic acid (PNA) probes for detection of Epstein
      Barr Virus (EBV) snRNA in fixed cells is described. Fluorescein labelled PNA
      probes were used to detect EBER1 and EBER2 snRNA in Raji, Daudi and HS-Sultan
      cells. The fixation and permeabilization of cells were optimized. The optimal
      fixation was found to be 5% acetic acid plus 4% paraformaldehyde in PBS and the
      optimal permeabilization 0.5% Tween 20 in PBS whereas no proteolytic digestion
      was needed. The hybridization time needed with the PNA probes was only 1 h. When
      running mixed samples of Ramos (EBV neg.) Raji, Daudi and HS-Sultan (EBV pos.)
      cells in flow cytometry a strong fluorescence signal was seen in Raji, Daudi and
      HS-Sultan cells whereas no fluorescence signal was seen in the Ramos cells. In
      total 0.5% EBER positive Raji cells could easily be identified in a mixture of
      Raji and Ramos cells. The results were verified by fluorescence microscopy. It is
      concluded that PNA probes can be used for in situ hybridization in solution and
      the analysis can be done using flow cytometry or fluorescence microscopy. PNA
      probes therefore may facilitate and enhance the potential use of the in situ
      hybridization/flow cytometry combination.

PMID- 9766888
TI  - Screening of horse polyclonal antibodies with a random peptide library displayed
      on phage: identification of ligands used as antigens in an ELISA test to detect
      the presence of antibodies to equine arteritis virus.
AB  - A random hexapeptide fusion-phage library was screened to isolate phages that
      bind to antibodies present in horse sera positive for equine arteritis virus
      (EAV). Analysis of the peptide sequences displayed by isolated phages identified
      seven groups. 25% of the isolated phages used as antigens in an ELISA test were
      specifically recognised by a pool of sera which was positive for EAV in virus
      neutralisation test (VN). Five of these, when used as antigen in ELISA, detected
      greater than 50% of sera (n = 30) containing antibodies to EAV as detected by VN.
      When these five phages were pooled together and used as antigen in ELISA, the
      detection was improved. The sensitivity and specificity of the ELISA were 99 and
      71%, respectively, compared with the EAV neutralisation test (n = 200). This
      study has shown the potential that phage display libraries have for identifying
      peptide sequences which could be used as antigen in diagnostic ELISAs.

PMID- 9766889
TI  - A sensitive and specific ELISA immunocapture assay for rapid quantitation of
      influenza A/H3N2 neuraminidase protein.
AB  - Both HA and NA proteins elicit antibodies which have been shown to be capable of
      altering the course of infection. Nevertheless, while influenza virus vaccine
      standardization involves hemagglutinin (HA) and neuraminidase (NA) in terms of
      antigenic characterization, only HA protein quantitation is undertaken. An
      immunocapture ELISA (EIA) is described for N2 NA quantitation, based on the use
      of a highly specific monoclonal antibody (MAb) for capturing NA and an anti-NA
      antiserum for antigen detection. The amounts of NA in samples were deduced from
      the standard curve established by using purified NA. The NA-EIA is specific and
      detects as a little as 7 ng/ml. The capture and detector antibodies directed
      against A/Beijing/32/92 NA were shown to react with H3N2 prototype strains used
      in current influenza vaccines, provided that an antigenically matched reference
      NA is used as standard.

PMID- 9766890
TI  - Antigenic characterization of canine parvovirus strains isolated in Italy.
AB  - 28 isolates of canine parvovirus type-2 (CPV-2) were obtained from dogs with
      hemorrhagic gastroenteritis in Italy. The antigenic structure of CPV-2 isolates
      was characterized, using four discriminating monoclonal antibodies. In addition,
      four vaccinal strains were examined. Similar to reports from Australia and the
      United Kingdom, a much higher prevalence of CPV-2a (25/28 isolates) was observed
      than the other variant type, CPV-2b (3/28 isolates). DNA fragments (2.2 kbp) of
      representative strains of CPV-2, CPV-2a and CPV-2b were amplified by the
      polymerase chain reaction (PCR) and the products were digested by the restriction
      enzymes (RE) RsaI, HpaII, HindIII and PvuII. The RvaI enzyme allows the
      differentiation of CPV-2 from CPV-2a and CPV-2b.

PMID- 9766891
TI  - A novel and innovative quantitative kinetic software for virological colorimetric
      assays.
AB  - This study addresses the limited range of quantification with colorimetric assays
      (ELISA) starting from the analysis of color production in a reference external
      curve. An automatic ELISA management software, designated Quanti-Kin Detection
      System (QKDS) is described, which retains the sensitivity of the end-point
      reading and extends the dynamic range up to five logarithms with mathematical
      interpretation of color production. The QKDS software is a generic system
      suitable for different types of ELISA with substrate incubation at room
      temperature, does not require dedicated instruments, performs accurate
      quantification (including assay quality control) and has a user friendly
      interface. Specific applications were developed for three types of analytes:
      antibodies, viral antigens and nucleic acids. Data are presented on three
      representative QKDS applications to HIV antibodies, p24 antigen and proviral DNA
      kits. The precision of quantification is strictly correlated with the precision
      of the kit; however, for almost all samples with known analyte amount, the error
      percentage was below 10%, only for two cases in quantification of HIV proviral
      DNA the error percentage was around 25%. The necessity for a wide quantification
      range has been demonstrated by measuring clinical samples, which showed a
      distribution in all possible quantification ranges for all kits.

PMID- 9766892
TI  - Hexon based PCRs combined with restriction enzyme analysis for rapid detection
      and differentiation of fowl adenoviruses and egg drop syndrome virus.
AB  - Three different polymerase chain reactions (PCRs), two of them combined with
      restriction enzyme analysis (REA), were developed for detection and
      differentiation of all 12 fowl adenovirus (FAV) serotypes and the egg drop
      syndrome (EDS) virus. For primer construction FAV1, FAV10 and EDS virus hexon
      proteins were aligned and conserved and variable regions were determined. Two
      primer sets (H1/H2 and H3/H4) for single use were constructed which hybridize in
      three conserved regions of hexon genes. Each primer pair amplifies approximately
      half of the hexon gene including two loop regions. An amplification product was
      detected with both primer sets using purified DNA from all FAV1-12 reference
      strains. Viral EDS DNA was negative using the H1/H2 or H3/H4 primer pair. HaeII
      digestion of the H1/H2 amplification products differentiates between all viruses
      except FAV4 and FAV5. In comparison, much more clustering among genomic closely
      related FAV serotypes was seen after HpaII digestion of the H3/H4 PCR products.
      Oligonucleotides H5/H6 located in the variable regions of EDS virus hexon gene do
      not detect any of the FAV serotypes. The PCRs and REA described are suitable to
      detect all avian adenoviruses infecting chickens, to distinguish all 12 FAV
      reference strains and to differentiate FAVs from the EDS virus.

PMID- 9766893
TI  - Purification of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) and
      analyses of the structural proteins.
AB  - The Kaposis's sarcoma-associated herpesvirus (KSHV) infected BCBL-1 cell line,
      adapted to and grown in medium containing 10% horse serum, was induced to lytic
      replication with 12-O-tetradecanoylphorbol-13-acetate (TPA) for virus production.
      Supernatants from induced cells were filtered through a 0.45-microm filter and
      virions were concentrated by polyethylene glycol extraction and high speed
      centrifugation. The virus was purified by a glycerol gradient zonal
      centrifugation step followed by isopycnic separation using positive density
      negative viscosity gradients. Two visible bands were detected after the final
      centrifugation step: an upper band that contained a homogenous population of
      purified virions and a lower band that contained aggregates of purified virus and
      other cellular debris. Fractionation of purified virion preparations by SDS-PAGE
      revealed 32 bands with estimated molecular weights between 19 and 280 K in silver
      stained gels. The glycoprotein bands in purified virus were identified with
      biotinylated lectins and horseradish peroxidase-labeled streptavidin. Two lectins
      were used to identify the KSHV glycoproteins: concanavalin A and Ricinus communis
      agglutinin I. Eight distinct glycoproteins were detected with these lectins. In
      addition, antisera from KS patients were used to detect immunoreactive proteins
      in purified virions. An apparent immunodominant band of Mr 94,000 (94 K) was
      recognized by patients' antisera. Other proteins detected with some of the KS
      antisera tested corresponded to molecular weights of 57 K, 70 K, 180 K, 200 K and
      240 K. The 94 K band was identified as gp94 by Endo F digestion.

PMID- 9766894
TI  - Microplate-reverse hybridization method to determine dengue virus serotype.
AB  - A reverse transcriptase-polymerase chain reaction (RT-PCR) and microplate-reverse
      hybridization method were developed to detect and type dengue viruses in patients
      plasma specimens. A silica method was used to isolate RNA; and 3'-noncoding
      region universal primers were used to amplify dengue virus RNA. Using RT-PCR and
      ethidium bromide staining we could detect dengue virus in serum spiked with
      serially diluted dengue virus with a level of sensitivity similar to that of a
      quantitative fluorescent focus assay of dengue viruses in cell culture, i.e. 1.4
      fluorescent focus units per reaction. Applying this assay to 14 dengue-positive
      plasma samples and 13 dengue-negative samples, dengue viremia was detectable by
      RT-PCR with a sensitivity comparable to mosquito inoculation. To determine the
      serotypes, digoxigenin-labeled PCR products from plasma samples and six
      laboratory adapted dengue viruses were hybridized in stringent conditions to
      serotype-specific DNA probes immobilized on microplates, and the hybridized
      product was detected with a colorimetric assay. Serotypes of dengue viruses, in
      cell culture and in patient plasma specimens, were identified using this method.

PMID- 9766896
TI  - Determination of nuclear DNA concentration in cells of Myxobolus cerebralis and
      triactinomyxon spores, the causative agent of whirling disease.
AB  - Myxobolus cerebralis (Myxozoa: Myxosporea) has a complex two-host life cycle,
      which begins when waterborne triactinomyxon spores released from the infected
      oligochaete Tubifex tubifex contact a susceptible trout. Upon contact the
      triactinomyxon spores attach to the fish and release their sporoplasm cells into
      the epidermis. At approximately 50 days postinfection, sporogenesis begins,
      resulting in a large number of M. cerebralis spores in the cartilage of infected
      fish 6 weeks later. The spores of M. cerebralis can be released from infected
      fish only after the fish die or are eaten by predators. In both cases, spores
      released into the aquatic environment can be ingested by oligochaete worms of the
      species T. tubifex and then develop into the actinosporean triactinomyxon stage
      in the intestine within about 3 months. The triactinomyxon is the only stage
      infectious for salmonid fish. We determined the DNA concentration in sporoplasm
      cells, capsulogenic cells, and valvogenic cells of M. cerebralis spore stages
      from the trout and of triactinomyxon spore stages from T. tubifex. DNA was
      visualized using the DNA-specific fluorescent stain DAPI. Our results demonstrate
      that meiosis occurs only once in the developmental cycle of M. cerebralis in
      contrast to the previously published hypothesis. This takes place within the
      pansporocyst found in T. tubifex. Thereafter, the sporoplasm cells of the
      triactinomyxon spores in T. tubifex and M. cerebralis in trout are diploid.

PMID- 9766895
TI  - Possible role of calmodulin in excystation of Giardia lamblia.
AB  - The protozoan Giardia lamblia initiates infection when trophozoites emerge from a
      cyst in the hosts by the excystation process. Although this process is crucial to
      the initiation of infection by G. lamblia, little is known about its regulation.
      To study the possible involvement of calmodulin (CaM) in excystation we tested
      the effect of several CaM antagonists (TFP, W-7, and W-5) on this cellular
      function. Except for W-5 the rest of these compounds inhibited excystation. The
      protein kinase C inhibitor H-7 had no effect on excystation, suggesting that CaM
      antagonists acted by selectively inhibiting CaM. Furthermore, CaM was
      redistributed after the induction of excystation and there was an increase in its
      fluorescence and activity. These results suggest that a CaM-dependent process is
      involved in G. lamblia excystation.

PMID- 9766897
TI  - Serodiagnosis of acute toxoplasmosis using a recombinant form of the dense
      granule antigen GRA6 in an enzyme-linked immunosorbent assay.
AB  - We developed an indirect enzyme-linked immunosorbent assay (ELISA) for the
      serological diagnosis of acute toxoplasmosis that used the recombinant granule
      antigen GRA6-GST as diagnostic antigen for the detection of IgG antibodies to
      Toxoplasma gondii in human sera. A total of 431 sera obtained from 336 patients
      with acute and chronic toxoplasmosis and from patients who were not infected with
      T. gondii were tested. Sera from patients with acute T. gondii infection, chronic
      infection, and no infection showed different absorbance values. For
      discrimination between the presence and the absence of acute toxoplasmosis the
      assay reached a specificity of 99.6%. Only one of the sera without significant
      anti-T. gondii. IgM antibodies showed a positive reaction to rGRA6-GST. The assay
      showed good intra- and interassay reproducibility (CV 6%/14%). We included a
      glutathione S-transferase (GST)-IgG enzyme immunoassay as a control assay in this
      study. Only 7 (4%) of 159 random sample sera reacted positively with GST.

PMID- 9766898
TI  - Characterization of Giardia duodenalis by polymerase-chain-reaction
      fingerprinting.
AB  - The development of a polymerase chain reaction (PCR) based fingerprinting method
      for the characterization of Giardia duodenalis isolates is described. The method
      uses three different PCRs; one is specific for the A ("Polish") major group of G.
      duodenalis isolates, another is specific for the B ("Belgian") group of isolates;
      and one amplifies a fragment of the glutamate dehydrogenase gene present in all
      G. duodenalis isolates. The PCRs perform highly sensitively on DNA from cultured
      trophozoites. Isolates were further characterized by restriction-fragment-length
      polymorphism (RFLP) analysis of the PCR products. In this way, representative
      isolates from the A and B groups could be grouped together into a number of
      subgroups. The stability of the genotypes with time and the reproducibility of
      the two methods were tested on cloned and subcloned lines from a number of
      isolates and proved to be highly satisfactory. The PCR/RFLP method was evaluated
      on cysts derived from a number of human patients. It is concluded that the PCR
      fingerprinting method described in this paper provides a reliable
      characterization method for Giardia isolates and has the potential to be used as
      a direct method of typing G. duodenalis cysts from feces.

PMID- 9766901
TI  - Host choice by larval parasites: a study of Biomphalaria glabrata snails and
      Schistosoma mansoni miracidia related to host size.
AB  - Within snail/trematode associations the age/size of the host at infection has
      consequences with regard to miracidial infection success, further intramolluscan
      parasite development and reproduction, and the host response, mainly in terms of
      growth and reproductive effort. Taking into account these differences, we were
      interested in determining whether miracidia could discriminate and make a choice
      between snails of different sizes. Using the Schistosoma mansoni/Biomphalaria
      glabrata system, we compared data on the snail infection rate and the mother
      sporocyst abundance among three size classes of snails (juvenile, subadult, and
      adult) exposed separately or together to the parasite larvae. When exposed
      individually, juvenile snails (3-5 mm) had significantly higher prevalence and
      abundance values than did subadult snails, followed by adult snails. In contrast,
      when snails of the three size classes were exposed together in heterogeneous size
      groups the prevalence and abundance values were always significantly higher for
      subadult snails of the 7- to 9-mm class than for juvenile and adult snails. A
      host choice experiment confirmed that significantly more miracidia were attracted
      by subadult snails, suggesting that the parasite has been selected for specific
      locating and recognition mechanisms increasing the infection rate of subadult
      snails when the latter have been exposed in a heterogeneous size group. Selective
      forces that may be responsible for such a preferential infectivity of the
      parasite vis-a-vis particular host age/size class are discussed in relation to
      host resources and host responses.

PMID- 9766899
TI  - The level of the collagen cross-link pyridinoline reflects the improvement of
      cutaneous lesions in one case of skin alveolar echinococcosis.
AB  - Cutaneous parasitic lesions, associated with a dense fibrous reaction, markedly
      improved under albendazole treatment in one case of supraumbilical skin
      localization of alveolar echinococcosis. Since collagen cross-linking increases
      during fibrogenesis and contributes to the stability of fibrotic lesions, we
      monitored the level of the cross-links pyridinoline and pentosidine in skin
      lesions from this patient to determine if they would reflect the changes
      occurring during treatment. We looked at the deposition of cross-linked type I
      collagen by immunohistochemistry and also measured the serum concentrations of
      pentosidine and of a fragment of type I collagen (ICTP), which contains a site of
      pyridinoline formation. Albendazole treatment did not affect either the collagen
      content of skin lesions or the serum concentrations of ICTP and pentosidine, but
      it led to a pronounced decrease in pyridinoline level concomitant with the
      disappearance, observed by immunohistochemistry, of extensively cross-linked
      fibrotic type I collagen. The follow-up of collagen cross-linking by pyridinoline
      in skin tissue thus appears to be useful in reflecting the improvement of
      fibrotic skin diseases during therapy.

PMID- 9766900
TI  - Effect of glucantime on field and patient isolates of New World Leishmania: use
      of growth parameters of promastigotes to assess antimony susceptibility.
AB  - The effect of pentavalent meglumine antimoniate (glucantime) on the growth
      kinetics of promastigotes of 13 South American Leishmania strains isolated from
      patients, sylvatic reservoirs, and vectors was studied. Four of five L. (Viannia)
      braziliensis human isolates were obtained from drug-responsive patients and one
      was isolated from an unresponsive mucocutaneous-type infection. Studies involved
      the cell yield at the late log phase, the growth rate, and the growth-curve
      patterns of promastigotes in vitro. Restriction-fragment-length polymorphism,
      pulsed-field gel electrophoresis, and hybridization with the gene coding for a P
      glycoprotein from L. (V.) guyanensis were used in an attempt to correlate the
      resistance phenotype with gene amplification. Consistent differences observed in
      both cell yield and growth rate among the isolates in the presence of glucantime
      indicated these parameters to be good criteria for the estimation of
      susceptibility to glucantime. Drug susceptibility varied widely between strains,
      indicating a great genetic heterogeneity of the isolates. Five L. (V.)
      braziliensis strains and three L. (V.) guyanensis strains were shown to be
      susceptible to glucantime. Five isolates were resistant, four of which were
      obtained from sylvatic vectors and one, from a patient with an unresponsive
      mucocutaneous infection. Molecular analyses of total DNA indicated the presence
      of a pgpA-related gene in all strains tested. No amplified sequence could be
      detected, suggesting that pgpA amplification is not involved in glucantime
      resistance in these wild Leishmania strains.

PMID- 9766902
TI  - Immunohistochemical characterization of a polyclonal antibody against
      Sphaerospora dicentrarchi (Myxosporea: Bivalvulida), a parasite from sea bass
      (Dicentrarchus labrax L.) (Teleostei: Serranidae).
AB  - Rabbit antibody was raised against Sphaerospora dicentrarchi, a histozoic
      parasite of sea bass (Dicentrarchus labrax L.). Light and electron
      immunohistological staining were used to characterize its specificity and
      possible reactivity toward other fish parasites. In light immunohistochemistry
      the polar capsules and valves of the S. dicentrarchi spores appeared strongly
      stained, whereas developmental stages were not. Electron microscopic
      histochemistry revealed intense labeling in valves and some developmental stages.
      Cross-reaction was observed with all the myxosporean parasites assayed, even with
      those belonging to other genera. Polar capsules of all the myxosporean species
      except Polysporoplasma sparis were the main structures stained by the polyclonal
      antibody. These observations could reveal the existence of conserved antigenic
      epitopes in polar capsules of different Myxosporea.

PMID- 9766903
TI  - Multiple bacteroids in the bacteriome of the lantern bug Pyrops candelaria Linn.
      (Homoptera: Fulgoridae).
AB  - Bacteriome in the lantern bug Pyrops candelaria harbored a-, t-, and companion
      bacteroids. The a- and t-bacteroids were irregular bodies, whereas the companion
      bacteroids were rod-shaped and easily distinguished from the others. The a- and t
      bacteroids were enveloped by three membranes and the companion bacteroids, by two
      membranes. The cytoplasm of the a-bacteroid contained electron-dense bodies.

PMID- 9766904
TI  - Amebicidal activity of plant extracts from Southeast Asia on Acanthamoeba spp.
AB  - The effect of 100 polar and 100 nonpolar plant extract materials obtained from
      Southeast Asia were evaluated for amebicidal activity in vitro against three
      species of Acanthamoeba. A. culbertsoni, A. castellanii, and A. polyphaga, the
      causative agents of granulomatous amebic encephalitis and amebic keratitis, were
      studied in vitro to determine whether the plant extracts exhibited amebicidal
      activity or induced encystment of the amebae. Of the 200 plant extracts tested,
      extracts obtained from three plants (Ipomoea sp., Kaempferia galanga, and Cananga
      odorata) were amebicidal for all three species of Acanthamoeba and a fourth
      extract prepared from Gastrochilus panduratum was lytic for A. polyphaga and
      growth-inhibitory for A. castellanii and A. culbertsoni. Three plant extracts
      induced encystment of all three species of Acanthamoeba. Select plant extracts
      were tested as well for tumoricidal activity against B103 neuroblastoma cells.
      Some plant extracts that exhibited tumoricidal activity for B103 cells were not
      amebicidal for Acanthamoeba spp. Additionally, the polar and nonpolar extracts
      that exhibited amebicidal activity were also tested for activity against primary
      murine peritoneal macrophage cultures. Plant extracts that demonstrated
      tumoricidal or amebicidal activity were not lytic for normal macrophage cultures.

PMID- 9766905
TI  - Longer-term population dynamics of Gyrodactylus bullatarudis and G. turnbulli
      (Monogenea) on adult guppies (Poecilia reticulata) in 50-I experimental arenas.
AB  - Two suprapopulations of monogeneans, one each of Gyrodactylus bullatarudis and G.
      turnbulli, on two groups of ten experimentally infected adult guppies (Poecilia
      reticulata) were maintained separately in 50.1 aquaria and monitored over 210
      days. The G. bullatarudis population had a pattern of initial growth, then a
      subsequent decline to extinction after 40 days. G. turnbulli, after initial
      population growth and decline, maintained low-intensity infections (0.33-3.3
      parasites/host) on six hosts over 94 days and did not become extinct during the
      experiment. There were some differences between the host-site specificity of G.
      bullatarudis and G. turnbulli on adult P. reticulata as compared with previously
      observed infections on immature fish.

PMID- 9766906
TI  - Characterization of levamisole binding sites in Trichinella spiralis.
AB  - Characterization of the levamisole receptor was performed with total extracts of
      Trichinella spiralis muscle larvae using binding assays with tritiated levamisole
      ([3H]LEV, 291 GBq/mmol). We detected a specific [3H]LEV binding activity with a
      dissociation constant (Kd) of 4.76 microM and a receptor density (Bmax) of 2.14
      pmol/mg of protein. In inhibition studies, only dimethylphenylpiperazinium iodide
      (DMPP) and hexamethonium were found to be competitive inhibitors of the [3H]LEV
      binding with an inhibition constant (Ki) of 31.04 and 4.43 microM, respectively,
      whereas d-tubocurarine and alpha-bungarotoxine had no effect on [3H]LEV binding
      activity, and procaine and atropine potentiated the [3H]LEV-receptor binding. All
      these data support the idea that levamisole acts as a cholinergic agonist in T.
      spiralis.

PMID- 9766907
TI  - Biochemical characterization of the Golgi-complex proteins of Tritrichomonas
      foetus.
AB  - Using cell-fractionation techniques (differential and discontinuous gradient
      centrifugation), we obtained a highly enriched fraction containing the Golgi
      complex of Tritrichomonas foetus. This fraction was further subfractionated by
      sodium carbonate (150 mM) treatment at pH 11.5, leading to the isolation of the
      Golgi content and membrane subfractions. Both fractions were characterized by
      electron microscopy. The protein content of membrane and luminal subfractions was
      about 40% and 60% of the total Golgi protein, respectively. Sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis analysis showed an enrichment of 15
      protein bands in the Golgi fraction, with molecular masses varying between 15 and
      116 kDa. Alkaline treatment released some proteins into the medium, but most of
      them were associated with the Golgi membrane.

PMID- 9766908
TI  - A recombinant protein disulfide isomerase homologue from Ancylostoma caninum.
AB  - The objective of this study was to characterize a recombinant antigen of
      Ancylostoma caninum that had been identified by immunoscreening with selected
      antisera as described elsewhere. In vitro expression of clone Ac38-1 produced a
      protein with an apparent molecular mass of approximately 38 kDa, which reacted in
      Western blots with the antiserum from rabbits experimentally infected with L3 and
      also with affinity-purified antibodies against hydrophilic proteins of the
      cephalic glands obtained from the antiserum against the intestine, cephalic
      glands, and cervical glands of adult worms. It was recognized not by antisera
      from dogs percutaneously infected with 1,000 L3 of A. caninum but by antiserum
      from dogs infected with 100,000 L3 of A. caninum. DNA sequencing of clone Ac38-1
      showed a cDNA fragment with a coding region of 1,014 bp. Comparison of clone Ac38
      1 with the Genbank DNA data base revealed 78% identity with a 244-bp segment of
      the cm5b5 clone of the free-living nematode Caenorhabditis elegans coding for a
      protein disulfide isomerase gene. The deduced amino acid sequence of clone Ac38-1
      showed 82% identity with a 334-amino-acid (aa) segment of the protein disulfide
      isomerase of C. elegans and 73% identity with a 334-aa segment of the protein
      disulfide isomerase aa sequence of Onchocerca volvulus.

PMID- 9766909
TI  - Occupational health in Australia.
AB  - Australia is a developed country in the Asia-Pacific Region with a large land
      area but a small population. Its main economic activities are mining, agriculture
      and manufacturing, with its service and high-technology industries being the
      fastest growing sectors in recent years. The regulation and enforcement of
      Occupational Health and Safety policies are mainly administered by the Industrial
      Relations Departments of eight State and Territory jurisdictions in the country.
      A National Occupational Health and Safety Commission coordinates occupational
      health and safety at the Commonwealth level. In 1987 the six occupational health
      and safety priorities in Australia were listed as occupational back pain,
      management of chemicals used at work, occupational noise-induced hearing loss,
      occupational skin disorders, occupational cancer and mechanical equipment injury.
      Australia has probably the highest incidence of malignant mesothelioma in the
      world, although the use of asbestos has been largely phased out. There was an
      almost explosive "epidemic" of repetition strain injury in the 1980s.
      Approximately 500 work-related fatalities and 10,000 work-related injuries are
      notified for workers' compensation every year. In addition, it is estimated that
      there are several thousand cases of work-related diseases every year, many of
      which go unreported. Occupational physicians undergo 4 years of specialisation
      training. Occupational hygienists, nurses and ergonomists receive training
      supervised by their respective professional organisations.

PMID- 9766910
TI  - Prevalence of irritative symptoms in a nonproblem air-conditioned office
      building.
AB  - OBJECTIVES: To assess the prevalence of work-related complaints and symptoms in
      employees in an air-conditioned office building (Building AC) in a mild climatic
      area (Italy). No discomfort had previously been reported. METHODS: A total of 198
      employees in Building AC and 281 controls working in three naturally ventilated
      buildings (Building NV) answered a questionnaire investigating work-related
      complaints and symptoms. RESULTS: A significantly higher percentage of workers in
      Building AC reported a lack of comfort in the working environment as compared
      with the controls (30.6% versus 18.9%). The most common complaints were strong
      lighting, high temperature, and dry, dusty, and/or stuffy air. The prevalence of
      ocular, upper airway, and cutaneous symptoms was significantly higher (29.8%
      versus 14.9%, 25.3% versus 9.6%, and 14.1% versus 3.6%, respectively). No
      significant difference was observed in respiratory or general symptoms. Logistic
      regression analysis showed that working with video display units and photocopiers
      influenced ocular symptoms; upper airway and cutaneous symptoms were influenced
      by female gender and working in the air-conditioned building. CONCLUSIONS: In an
      apparently healthy air-conditioned office building, complaints and symptoms are
      reported more often than in a naturally ventilated edifice, but the prevalence is
      lower than that usually observed in sick buildings. Symptoms are influenced by
      individual and work-related characteristics.

PMID- 9766911
TI  - Assessment of environmental tobacco smoke and respirable suspended particle
      exposures for nonsmokers in Prague using personal monitoring.
AB  - OBJECTIVE: Exposures to respirable suspended particles (RSP) and environmental
      tobacco smoke (ETS) were assessed in Prague, Czech Republic, to determine the
      range and degree of personal exposure by means of personal monitoring over a 24-h
      period. DESIGN: Self-reported nonsmokers were randomly selected from a
      representative sample of the population of Prague. Housewives were recruited into
      one group, primarily for assessment exposures in the home, and office workers
      were recruited into a second group for assessment of the contribution from the
      workplace. METHODS: A total of 238 randomly selected nonsmoking subjects
      collected air samples near their breathing zone by wearing personal monitors for
      24 h. Samples collected were analyzed for RSP, nicotine, 3-ethenylpyridine, and
      ETS particles (using ultraviolet absorbance, fluorescence, and solanesol
      measurements). Saliva cotinine analyses were also undertaken to confirm the
      nonsmoking status of the subjects. RESULTS: The most highly exposed subjects in
      this study were office workers both living and working with smokers. Median time
      weighted average exposure concentrations of 60 microg m(-3)RSP, 16 microg m(
      3)ETS particles, and 1.6 microg m(-3) nicotine were determined for these
      subjects, who also had the highest median saliva cotinine level of 2.4 ng ml(-1).
      Housewives living in nonsmoking households were the least exposed subjects in
      this study, showing levels of 32 microg m(-3) RSP, 0.17 microg m(-3) ETS
      particles, and 0.15 microg m(-3) nicotine. As based upon median levels of ETS
      particles and nicotine, no group would potentially inhale or be exposed to more
      than 10 cigarette equivalents per year (CE/y) and the least exposed would inhale
      less than 1 CE/y. The most highly exposed (90th percentile levels) nonsmokers in
      this study, who both worked and lived with smokers, would potentially inhale up
      to 29 CE/y. Overall, the workplace was estimated to contribute between 45% and
      49% of the annual exposure to nicotine and ETS particles, respectively. On the
      basis of determined saliva cotinine concentrations, a misclassification rate of
      between 1.7% and 2.5% was calculated. CONCLUSION: Highest exposures were apparent
      for office workers both working and living in smoking environments. and our
      findings suggest a significant contribution to overall ETS particle and nicotine
      levels from the workplace where smoking takes place. Overall, the rates at which
      subjects were determined to have misclassified their smoking status in this study
      were the lowest observed in any of the European cities investigated to date.
      Clearly, a more sensitive method of analysis for cotinine in body fluids is
      needed for more accurate determination of the levels expected for nonsmokers.

PMID- 9766912
TI  - Exposure to methyl tert-butyl ether and tert-amyl methyl ether from gasoline
      during tank lorry loading and its measurement using biological monitoring.
AB  - OBJECTIVE AND METHODS: The exposure of Finnish tank lorry drivers to methyl tert
      butyl ether (MTBE) and tert-amyl methyl ether (TAME) during loading of gasoline
      was studied using biological and breathing-zone sampling. During the field
      measurements in October 1994 and August 1995 the gasolines (95, 98, 99 RON)
      contained MTBE to 5.2-11.8% and TAME to 0-6%. RESULTS: The geometric mean (GM)
      breathing-zone concentration of MTBE was 4.3 mg/m3 (n = 15) in October and 6.4
      mg/m3 (n = 20) in August. The GM concentration of TAME, measured only in August,
      was 0.98 mg/m3. The mean loading/sampling times were 37 and 35 min, the mean wind
      speeds were 0.8 and 0.6 m/s, and the mean air temperatures were -4.9 degrees and
      + 14.1 degrees C, respectively. Blood samples collected on average at 20 min
      after gasoline loading/exposure showed an MTBE concentration of 143 nmol/l (GM, n
      = 14) in October and 213 nmol/l (GM, n = 20) in August. Pearson's coefficient of
      correlation (r) between the MTBE breathing-zone concentrations and MTBE in blood
      was 0.86 (P = 0.0001) in October and 0.81 (P = 0.00001) in August. No correlation
      was found between MTBE in air and the metabolite tert-butanol (TBA) in blood.
      MTBE, but not TBA, in urine samples collected on average at 2.5 h after exposure
      showed a correlation with MTBE in air. The concentrations of TAME and its
      metabolite tert-amyl alcohol were below the quantitation limits ( < 7 and < 100
      nmol/l, respectively) in most blood and urine samples. CONCLUSIONS: The breathing
      zone measurements showed low levels of exposure to the two oxygenates, the
      concentrations being well below the current hygienic standards for MTBE (250-360
      mg/m3 for 15 min and 90-180 mg/m3 for 8 h). The linear correlations obtained for
      MTBE suggest that MTBE in blood or urine can be adopted as a valid biological
      exposure index.

PMID- 9766913
TI  - Monitoring of occupational exposure to dichloromethane by diffuse vapor sampling
      and urinalysis.
AB  - OBJECTIVE: The aim of the present study was to develop valid methods for
      monitoring of occupational exposure to dichloromethane (DCM). METHODS: Carbon
      cloth as an adsorbent in diffusive sampling was tested for its capacity to adsorb
      DCM vapor and to retain adsorbed DCM after termination of the exposure. Urine
      samples collected from DCM-exposed workers were analyzed for DCM by the head
      space technique. After extraction with carbon disulfide, DCM in the cloth was
      analyzed on a DB-WAX capillary column by flame-ionization detection gas
      chromatography (FID-GC) and DCM in urine was analyzed by electron-capture
      detection (ECD)-GC. RESULTS: The diffusive sampling with carbon cloth as an
      adsorbent is applicable to 4-h monitoring of exposure to up to 100 ppm DCM vapor.
      DCM concentrations detected in end-of-shift urine samples correlated linearly
      with time-weighted average DCM concentrations measured in the breathing-zone air
      of the exposed workers; essentially the same exposure-excretion relationship was
      obtained by vapor monitoring for the afternoon 4-h period as compared with a
      whole day (8-h) of vapor monitoring. There was no sex difference in the exposure
      excretion relation. CONCLUSIONS: Both personal diffusive sampling (at up to 100
      ppm DCM and for up to 4 h) and biological exposure monitoring by urinalysis for
      DCM are applicable in occupational health as reliable measures of exposure to
      this chlorinated hydrocarbon solvent.

PMID- 9766914
TI  - Elevated liver enzyme activity in construction workers: prevalence and impact on
      early retirement and all-cause mortality.
AB  - BACKGROUND: Gamma-glutamyl transferase (GGT), alanine transaminase (ALT), and
      aspartate transaminase (AST) are widely used as markers of hepatobiliary
      disorders in occupational health surveillance. Little is known, however, about
      the prevalence and occupational and non-occupational determinants of elevated
      levels of these enzymes in specific occupational groups or about the prognostic
      value of elevated levels with respect to long-term outcomes such as all-cause
      mortality and vocational disability. METHODS: A cohort study was conducted among
      8,043 male construction workers aged 25-64 years who had undergone occupational
      health examinations in 6 centers in southern Germany from 1986 to 1988 and had
      been followed until 1994. The prevalence of elevated levels of GGT, ALT, and AST,
      depending on the sociodemographic and medical characteristics determined at the
      baseline examination and the risk of vocational disability and all-cause
      mortality in relation to elevated liver enzyme activity at baseline were
      assessed. Covariates considered in multivariate analysis included age,
      nationality, occupation, body mass index (BMI), smoking, and alcohol consumption.
      RESULTS: The baseline prevalence of elevated activity levels of GGT (>28 U/1 at
      25 degrees C), ALT (>22 U/1), and AST (>18 U/1) was 32%, 22%, and 12%,
      respectively. Factors most strongly related to elevated serum activity levels for
      all three enzymes were self-reported alcohol consumption, diabetes, and
      hypertension. BMI was strongly associated with elevations in GGT and ALT but not
      in AST. Elevated levels of AST and GGT were strongly related to early retirement
      and all-cause mortality. Men with AST levels exceeding 18 U/1 had a 2-fold risk
      of early retirement and a 3 times higher risk of all-cause mortality as compared
      with men with lower AST levels. No significant association was observed between
      ALT and either of the long-term outcomes. CONCLUSIONS: Our findings suggest that
      screening for elevated GGT and AST levels, which are a common finding among
      construction workers, may be a powerful tool for the identification of
      individuals at increased risk of early retirement and preterm mortality and may
      be helpful in targeting of prevention efforts.

PMID- 9766915
TI  - Effect of environmental temperature on the interactive developmental toxicity of
      radiofrequency radiation and 2-methoxyethanol in rats.
AB  - OBJECTIVE: This research was conducted to determine if altered environmental
      temperatures would affect the interactive developmental toxicity of
      radiofrequency (RF) radiation and the industrial solvent, 2-methoxyethanol (2ME).
      This is important because RF radiation is used in a variety of workplaces that
      have poorly controlled environmental temperatures, and many workers are
      concurrently exposed to various chemicals. Furthermore, we have previously
      demonstrated that combined exposure to RF radiation (10 MHz) and 2ME produces
      enhanced teratogenicity in rats. METHODS: RF radiation sufficient to maintain
      colonic temperatures at the control value (38degrees ), 39.0degrees or 40.0
      degrees C for 2 or 4 h combined with either 0 or 100 mg/ kg 2ME at environmental
      temperatures of 18 degrees , 24 degrees and 30 degrees C (65 degrees , 75 degrees
      , and 85 degrees F) were given on gestation day 13 to Sprague-Dawley rats. Dams
      were killed on gestation day 20, and the fetuses were examined for external
      malformations. RESULTS AND CONCLUSIONS: Environmental temperature does affect the
      specific absorption rate (SAR) necessary to maintain a specific colonic
      temperature but does not affect the interactive developmental toxicity of RF
      radiation and 2ME in rats. These results, consistent with the literature, add to
      the evidence that the developmental toxicity of RF radiation (combined or alone)
      is associated with colonic temperature, not with SAR.

PMID- 9766916
TI  - Distribution of nickel in lungs from former nickel workers.
AB  - OBJECTIVE: The purpose of this work was to study the distribution of nickel
      within lung tissue obtained from nickel-exposed people and to evaluate the use of
      only one single sample for determination of the nickel burden of the lung.
      METHODS AND MATERIALS: The material used was lung tissue obtained from 15 former
      nickel refinery workers who had been exposed to a variety of nickel compounds
      such as Ni3S2, NiO, Ni0, NiSO4, and NiCl2. Ten samples taken from different
      locations of the lung as well as from the right and left bronchus and from the
      right lower lobe (total 13 samples per individual) were analyzed for nickel by
      electrothermal atomic absorption spectrometry. Samples obtained from ten people
      not connected to the refinery served as a reference group. RESULTS: The
      arithmetic mean value +/-SD for nickel concentration was 50+/-150 microg g(-1)
      dry wt. Biopsies collected on the center of the lower right lobe had an average
      nickel concentration of 82+/-252 microg g(-1). The average nickel concentration
      detected in the right and left bronchus was 5.9+/-11.6 and 3.8+/-6.0 microg g(
      l), respectively. Lung tissue obtained from ten people not connected to the
      refinery had an average nickel concentration of 0.74+/-0.44 microg g(-1).
      CONCLUSIONS: The significant findings based on log-normal distribution of the
      nickel concentration were as follows: (1) samples obtained from the right lung
      showed no significant difference from samples taken from the left lung-a
      comparison of the nickel concentration detected in all the lung lobes showed that
      no single lobe differed from another; (2) the concentration of nickel found in
      the main bronchus of the refinery workers, although elevated, was significantly
      lower than the concentration detected in the remaining tissue; and (3) one single
      biopsy did not reflect the nickel burden of the lung.

PMID- 9766917
TI  - Job strain and arterial blood pressure, serum cholesterol, and smoking as risk
      factors for coronary heart disease in Japan.
AB  - OBJECTIVE: To determine the effects of the job demands-control model on arterial
      blood pressure, serum total cholesterol, and smoking in male daytime and rotating
      shift workers in Japan. METHODS: The survey was conducted for all employees of an
      electrical factory in Japan using a mailed questionnaire concerning three job
      stressors, i.e., job overload, work-pace control, and work-site social support. A
      blood sample was taken at the same time. Data on 1703 male daytime workers and 1
      173 male rotating-shift workers were analyzed. Multiple logistic regression or
      analysis of covariance (ANCOVA) were employed to determine the effects of the job
      stressors on systolic and diastolic blood pressure, serum total cholesterol, and
      smoking with control for other covariates. RESULTS: Among daytime workers,
      systolic and diastolic blood pressures were highest in the "high-strain" (i.e.,
      higher job overload + lower work-pace control) group; ANCOVA indicated that a two
      way interaction between job overload and work-pace control was significant (P <
      0.01). This tendency was not observed among rotating-shift workers. The number of
      cigarettes smoked per day was greater in groups with lower work-pace control and
      lower work-site social support among daytime workers (two-way interaction between
      these two job stressors, P < 0.05); it was greater in groups with lower work-site
      social support among rotating-shift workers (main effect of work-site social
      support, P < 0.05). CONCLUSIONS: Our study suggest that job strain as defined in
      the job demands-control model is associated with increased systolic and diastolic
      blood pressures in male daytime workers in Japan. Smoking might be affected by
      lower work-site social support.

PMID- 9766918
TI  - Hairy cell leukemia. What is new forty years after the first description?
AB  - Hairy cell leukemia represent 2% of all the leukemias. The etiology is unknown.
      The diagnosis is based on the peripheral blood examination, showing
      characteristic lymphoid B cells, with loose lacy chromatin and unconstant
      cytoplasmic projections. The abnormal lymphoid cells express CD19, CD20, CD22,
      CD79a, CD25 and CD103. The tumor cells are Sig + with clonal light chain
      restriction. The treatment is based on recombinant IFN: we discuss the interest
      and the risks of second malignancy related to the prescription of the purine
      analogues.

PMID- 9766919
TI  - Clinical, morphological, cytogenetic and molecular aspects of a series of Ph
      negative chronic myeloid leukemias.
AB  - Clinical, morphological, cytogenetic and molecular (fluorescence in situ
      hybridization and RT-PCR) data were analyzed in twelve Philadelphia negative
      chronic myeloid leukemias (Ph-negative CMLs). Four patients were classified as
      BCR-positive. A standard b2a2 or b3a2 transcript was found, and the BCR-ABL
      hybrid gene was located on the 22q11 band in three cases and on the 1p35 band in
      one case with a t(1;9)(p35;q34). All were classified as typical chronic
      granulocytic leukemia (CGL) according to the French-American-British (FAB)
      morphological guidelines. Responses to therapy were evaluated by FISH in the four
      patients, and proved to be poorer than in Ph-positive CMLs. Eight BCR-negative
      patients were identified. They could be characterized by an older age, a less
      proliferative form of disease than the BCR-positive patients, and a frequent (six
      out of eight) abnormal karyotype. The FAB classification identified four CGLs and
      four atypical CMLs (aCML). A normal karyotype was more frequent in the patients
      classified as CGL whereas all the aCMLs had a chromosomal abnormality. Three
      patients had chromatin clumping and this morphologic feature was associated with
      trisomy 8 in two. No correlation between the cytogenetic, morphologic and the
      clinical data were found. Five patients had poor tolerance to therapy with a
      frequent occurrence of bone marrow failure and hemorragic syndrome, whereas three
      patients responded to a standard treatment of CML. Our study reinforces previous
      data on Ph-negative BCR-positive CMLs and emphasizes the difficulty in
      correlating clinical, morphologic, cytogenetic data in Ph-negative BCR-negative
      CMLs. However, our data also argue in favor of the existence of true Ph-negative
      BCR-negative CMLs and suggest that some of them can respond to a standard
      treatment of CML.

PMID- 9766920
TI  - Epidemiological data in polycythaemia vera: a study of 842 cases.
AB  - An epidemiological study of 842 polycythaemic patients (entered between 1980 and
      1997 in the French investigational prospective protocols) is presented. The
      global incidence is approximately 0.8-1.5/100,000/year in the reference area (Ile
      de-France and surrounding areas). It increases linearly with age until 80, which
      suggests that several mutational somatic events are necessary. There was a slight
      male excess (sex-ratio 1.2, after correction for the percentage of male and
      female French people still living at risk). We did observe a slight excess of PV
      in the population of Jewish ancestry. A surprising excess of former blood donors
      (20.7% of the PV cases, compared to 8% estimated in the reference population) was
      observed. Only a few cases of familial myeloproliferative diseases and occurence
      of leukemia in the family of our patients have been observed; even if slight,
      this excess is statistically significant. In contrast, no excess of carcinomas
      was observed either in the family or in the patients' antecedents. We did not
      find any excess of radiation exposure in our cases. When analysing the previous
      occupation of our patients a possible excess of physicians and of patients
      previously working in occupations using solvents and glues was found, but this
      finding needs confirmation.

PMID- 9766921
TI  - Severe infection caused by Stomatococcus mucilaginosus in a neutropenic patient:
      case report and review of the literature.
AB  - A 24-year-old female, in neutropenic phase after chemotherapy for acute
      myelogenous leukemia (on day 15) was admitted in intensive care unit for
      infectious pneumonia. Two strains of Stomatococcus mucilaginosus were isolated
      from peripheral blood cultures. No microorganisms were yielded from
      bronchoalveolar lavage. Patient's condition improved with prompt instigation of
      effective antibiotic therapy. This was the first case of septicemia and
      pneumonia, due to Stomatococcus mucilaginosus, in our unit. Only 26 cases
      occurring in neutropenic patients with underlying hematologic malignancies were
      reported in the literature and among these, only five cases with pneumonia were
      described. The complications of this normal inhabitant of the human oral cavity
      can be serious and fatal: septic shock, meningitis, acute respiratory distress
      syndrome. This study illustrate the possible virulence of Stomatococcus
      mucilaginosus in neutropenic patients.

PMID- 9766922
TI  - Prognostic and diagnostic value of endogenous erythroid colony formation in
      essential thrombocythemia.
AB  - Endogenous erythroid colonies (EECs), a typical characteristic of polycythemia
      vera (PV), could be observed in essential thrombocythemia (ET). Erythroid
      progenitors culture carried out in 34 previously untreated patients with
      unequivocal ET showed EECs in 35% of the cases. During a mean follow up of 4
      years after the culture, the 12 EECs(+) and the 22 EECs(-) patients did not show
      any difference for a thrombotic or haemorrhagic complication, and the only one
      patient who showed an involvement of erythropoiesis was in the EECs(-) group.

PMID- 9766923
TI  - Screening of cobalamin metabolism in methotrexate-treated psoriatics.

PMID- 9766924
TI  - SCAR 98. Proceedings of the 15th symposium for computer applications in
      radiology: filmless radiology--reengineering the practice of radiology for the
      21st century. Baltimore, Maryland, USA. June 4-7, 1998.

PMID- 9766925
TI  - Recent Advances in Surfactant Research. Proceedings and abstracts of the 13th
      International Workshop on Surfactant Replacement. Belfast, September 12, 1998.

PMID- 9766926
TI  - [Prevention, screening, and management of cancer of the colon. Agence Nationale
      d'Accreditation et d'Evaluation en Sante].

PMID- 9766927
TI  - Society for Research on Nicotine and Tobacco. Third Annual Scientific Conference,
      Nashville, Tennessee, USA, 13-14 June 1997.

PMID- 9766928
TI  - New drug treatments for alcohol problems. Response to Moncrieff & Drummond.

PMID- 9766929
TI  - Plucked hair samples as a source of DNA: reliability of dinucleotide
      microsatellite genotyping.
AB  - To test whether plucked hairs are a reliable source of DNA for genotyping
      microsatellite loci, we carried out experiments using one, three, or 10 hairs per
      extract for 50 alpine marmots. For each extract, seven independent genotypings
      were performed for the same locus (multiple-tubes approach). Two types of
      genotyping errors were recorded: a false homozygote defined as the detection of
      only one allele of a true heterozygote, and a false allele defined as a PCR
      generated allele that was not one of the alleles of the true genotype. Using DNA
      extracted from one, three, or 10 hairs the overall error rate was 14.00%, 4.86%,
      and 0.29%, respectively. Based on our results, we conclude that 10 hairs should
      be used to obtain consistently reliable genotypings using the single-tube
      approach, and that a single plucked hair could represent a reliable source of DNA
      if the multiple-tubes approach is used. For future studies of dinucleotide repeat
      diversity using DNA extracted from one to three shed or plucked hairs, we
      strongly recommend initiating an appropriate pilot study to quantify the error
      rate and to determine the reliability of the single-tube approach.

PMID- 9766930
TI  - Proceedings of the 1st Annual OR-Acquired Pressure Ulcer Symposium. Atlanta,
      Georgia, USA.

PMID- 9766931
TI  - Establishing a Medical Research Agenda for Child Sexual Abuse: An Invitational
      Conference. Solitude, Utah, USA. May 16-17, 1997. Proceedings.

PMID- 9766932
TI  - Taking the p... therapeutic proteins from urine.

PMID- 9766933
TI  - [Fifty years after the creation of the chair at the Medical School of Bucharest].

PMID- 9766934
TI  - Automated 3-dimensional computed tomographic and fluoroscopic image registration.
AB  - The registration of 3-dimensional (3-D) anatomical surfaces to sensor data such
      as intraoperative fluoroscopy is one of the basic problems in computer integrated
      surgery. The main objective is to find the relationship between 3-D preoperative
      computed tomographic images and a pair of intraoperative fluoroscopic images.
      Consequently, surgical navigation devices can use this relationship to provide
      improved surgical guidance. The proposed registration strategy presents a
      noninvasive anatomy-based (frameless) method for registration. In this article,
      we propose a cooperative approach between registration and contour segmentation
      on fluoroscopy. This approach is based on the duality between registration and
      segmentation in a model-based vision system. It associates a likelihood value to
      each pixel that corresponds to the probability that the pixel belongs to the
      contour of the object of interest. The registration is then achieved between
      backprojection lines stemming from likely contour pixels and the 3-D surface
      model of the object of interest. Then, in order to take into account the internal
      contour points extracted by the cooperative approach, we propose a new line to
      surface distance computation algorithm to be used during the data to model
      distance minimization step. Finally, we present the obtained results that
      demonstrate the validity of the proposed approach in carrying out accurate 3-D
      and 2-D registration.

PMID- 9766935
TI  - Hepatitis B vaccination of patients with chronic liver disease.

PMID- 9766936
TI  - Patient survival after tertiary liver transplantation.

PMID- 9766937
TI  - Helmut Heydt--friend and counsellor.

PMID- 9766938
TI  - The EDSP: setting the stage!

PMID- 9766940
TI  - Taking the ocean's temp.

PMID- 9766939
TI  - Plant lectins: specific tools for the identification, isolation, and
      characterization of O-linked glycans.

PMID- 9766941
TI  - A move for the better.

PMID- 9766942
TI  - A gray area of environmental justice.

PMID- 9766943
TI  - A nice cup of tea.

PMID- 9766944
TI  - A breath of fresh air.

PMID- 9766945
TI  - Double-edged sword.

PMID- 9766946
TI  - Bug spray worse than the bite?

PMID- 9766947
TI  - Ambivalent antihistamines.

PMID- 9766948
TI  - Meeting of the cancer minds.

PMID- 9766949
TI  - Taking the lead on lead.

PMID- 9766950
TI  - To MTBE or not to MTBE.

PMID- 9766951
TI  - Decade of the brain: the gray area of research on gray matter.

PMID- 9766952
TI  - Environmental impact on hearing: is anyone listening.

PMID- 9766953
TI  - Methyl bromide under fire.

PMID- 9766954
TI  - Vets may be compensated.

PMID- 9766955
TI  - Poland's environmental docs.

PMID- 9766956
TI  - Cigarette secrets.

PMID- 9766957
TI  - World Wildlife funds for Russia and Asia.

PMID- 9766958
TI  - Cystic fibrosis: present and future.
AB  - Cystic fibrosis (CF) is an inherited disorder of epithelial chloride transport
      affecting primarily pancreas, lungs, gut, liver and exocrine glands. The defect
      is caused by defects of the cystic fibrosis transmembrane regulation gene on
      chromosome 7. Genotyping has proved useful in identifying gene carriers, a
      definitive diagnosis, and in antenetal diagnosis. Genotype/phenotype
      relationships have shown that the commonest cause of pancreatic insufficiency is
      the D F508 mutation. Clinical trials are exploring the use of somatic gene
      therapy but this is not yet a viable treatment option. Liver, lung and intestinal
      disease result in malnutrition which causes further dysfunction of these organs.
      Aggressive nutritional and pancreatic enzyme therapy results in improved disease,
      normal growth and increased survival. However, high-dose enzyme therapy may in
      some individuals cause a fibrosing colonopathy. For those with end-stage liver
      and lung disease, transplantation holds out some hope.

PMID- 9766959
TI  - The amount and pattern of DNA polymorphism under the neutral mutation hypothesis.
AB  - The amount and pattern of DNA polymorphism can give useful information on the
      maintenance mechanism of genetic variation at the DNA level. In this note we have
      shown the amount and pattern of DNA polymorphism expected under the neutral
      theory. The amount of DNA polymorphism can be estimated from the average number
      of nucleotide differences per site, the proportion of segregating sites, and so
      on. We have shown how to estimate theta from these quantities, where theta = 4Nv,
      N is the effective population size and v is the mutation rate per site per
      generation. We have also shown the expectations of the nucleotide variation
      within and between allelic classes.

PMID- 9766960
TI  - Risk of population extinction from fixation of deleterious and reverse mutations.
AB  - A model is developed for alternate fixations of mildly deleterious and wild-type
      alleles arising by forward and reverse mutation in a finite population. For
      almost all parameter values, this gives an equilibrium load that agrees closely
      with the general expression derived from diffusion theory. Nearly neutral
      mutations with selection coefficient a few times larger than 1/(2N(e)) do the
      most damage by increasing the equilibrium load. The model of alternate fixations
      facilitates dynamical analysis of the expected load and the mean time to
      extinction in a population that has been suddenly reduced from a very large size
      to a small size. Reverse mutation can substantially improve population viability,
      increasing the mean time to extinction by an order of magnitude or more, but
      because many mutations are irreversible the effects may not be large. Populations
      with initially high mean fitness and small effective size, N(e) below a few
      hundred individuals, may be at serious risk of extinction from fixation of
      deleterious mutations within 10(3) to 10(4) generations.

PMID- 9766961
TI  - Asymmetrical DNA replication promotes evolution: disparity theory of evolution.
AB  - Heredity is guaranteed by faithful DNA replication whereas evolution depends upon
      errors accompanying DNA replication. This contradiction existing between heredity
      and evolution cannot be resolved in an individual organism, but only in terms of
      a population, in that a delicate balance exists between wild type and variants in
      a population which is necessary for the survival of the species. Namely, there
      seems to be a key in the mechanism of DNA replication to solve some problems of
      evolution. DNA is replicated semiconservatively using the leading and
      discontinuous lagging strands. According to our 'disparity theory of evolution',
      the existence of a sufficient fidelity difference between the leading and lagging
      strands is advantageous in terms of evolution, because the diversity of genotypes
      is enlarged but genotypes that have occurred in the past are guaranteed. In
      theory, by artificially increasing the fidelity difference between the leading
      and lagging strand ('disparity mutator'), evolution is accelerated while avoiding
      the extinction of the population. Using a disparity mutator, we should be able to
      improve living things, including multicellular organisms, within constrained
      conditions. A double-stranded algorithm, which mimics the structure and
      replication manner of DNA, is promising for solving optimization problems.

PMID- 9766962
TI  - Clusters of new identical mutants and the fate of underdominant mutations.
AB  - Given favorable environmental and demographic conditions, premeiotic clusters of
      identical mutations can produce a broad distribution of the initial frequency of
      underdominant alleles. Because of these clusters, new underdominant mutations may
      not necessarily be as rare in a population as previously assumed. The fixation of
      underdominant mutations, especially those with low heterozygous fitness, is
      increased when mutations appear in a cluster due to a genetic change that
      occurred before germline differentiation. Most restrictions on the fixation of
      underdominant mutations in a single population, such as strong genetic drift,
      weak selection against mutant heterozygotes, isolated population structure,
      inbreeding, meiotic drive, and selection in favor of mutant homozygotes can be
      relaxed or even dropped. Instead, the fate of strong underdominant mutations is
      determined mainly by ecological and genetic factors that affect the cluster size
      distribution of new premeiotic mutations. Accumulation of reproductive isolation
      by the fixation of underdominant mutations becomes more feasible with clusters,
      and mutation is not always the weakest force during this evolutionary process.
      The large mean and variance of reproductive success in many multicellular species
      make it possible that even underdominant mutations with very low heterozygous
      fitness could contribute substantially to reproductive isolation.

PMID- 9766963
TI  - Mutation and selection within the individual.
AB  - Selection within the individual may have played a critical and creative role in
      evolution, boosting the survival chances of mutations beneficial to the cell and
      the individual, hindering the spread of deleterious mutations, and reducing the
      genetic load imposed on the population. We review the literature and present new
      results to describe the effects of cell-lineage selection on the rate and
      fixation probability of new mutations. Cell-lineage selection can alter these
      quantities by several orders of magnitude. Cell-lineage selection is especially
      important in the case of rare recessive mutations, which are hidden from
      selection at the individual level but may be exposed to selection at cellular
      level. Because selection within the individual acts as a sieve eliminating
      deleterious mutations and increasing the frequency of beneficial ones, mutations
      observed among progeny will have been pre-selected and are more likely to
      increase cell proliferation than would randomly generated mutations. Although
      many authors have focused on the potential conflict between selection at the
      cellular and individual levels, it must be much more common that the two levels
      act concordantly. When selection at the cell and individual levels act in a
      cooperative manner, increased rather than decreased opportunity for germline
      selection will be favored by evolution.

PMID- 9766964
TI  - A pleiotropic model of phenotypic evolution.
AB  - A pleiotropic model is presented for deriving the equilibrium genetic variance by
      mutation and stabilizing selection and the long-term genetic responses to
      directional selection in the case where mutations have pleiotropic effects on
      fitness itself (direct deleterious effect) and on a quantitative trait
      (phenotypic effect). The equilibrium genetic variance is derived as a general
      form of the rare-alleles models, i.e., [formula: see text], where n is the number
      of loci, mu is the per-locus mutation rate, alpha 2 is the variance of new
      mutations, V(s) is the measure of stabilizing selection, and s(u) is the
      selection coefficient on mutations by direct deleterious effect. The genetic
      responses to directional selection is calculated based on the assumption that the
      genetic variance is kept at an equilibrium by mutation and stabilizing selection
      but without directional selection, and the directional selection starts to
      operate on the target trait. The evolutionary rate at the t-th generation after
      the introduction of the directional selection is [formula: see text], where i is
      the directional selection intensity, and s(T) is the total selection coefficient
      on mutations, i.e., [formula: see text]. The selection limit is [formula: see
      text], where V(m) is the mutational variance (2n mu alpha 2). The pleiotropic
      effects of genes reduce both the evolutionary rate and the selection limit.

PMID- 9766965
TI  - Genetic measurement of theory of epistatic effects.
AB  - Epistasis is defined as the influence of the genotype at one locus on the effect
      of a mutation at another locus. As such it plays a crucial role in a variety of
      evolutionary phenomena such as speciation, population bottle necks, and the
      evolution of genetic architecture (i.e., the evolution of dominance,
      canalization, and genetic correlations). In mathematical population genetics,
      however, epistasis is often represented as a mere noise term in an additive model
      of gene effects. In this paper it is argued that epistasis needs to be scaled in
      a way that is more directly related to the mechanisms of evolutionary change. A
      review of general measurement theory shows that the scaling of a quantitative
      concept has to reflect the empirical relationships among the objects. To apply
      these ideas to epistatic mutation effects, it is proposed to scale A x A
      epistatic effects as the change in the magnitude of the additive effect of a
      mutation at one locus due to a mutation at a second locus. It is shown that the
      absolute change in the additive effect at locus A due to a substitution at locus
      B is always identical to the absolute change in B due to the substitution at A.
      The absolute A x A epistatic effects of A on B and of B on A are identical, even
      if the relative effects can be different. The proposed scaling of A x A epistasis
      leads to particularly simple equations for the decomposition of genotypic
      variance. The Kacser Burns model of metabolic flux is analyzed for the presence
      of epistatic effects on flux. It is shown that the non-linearity of the Kacser
      Burns model is not sufficient to cause A x A epistasis among the genes coding for
      enzymes. It is concluded that non-linearity of the genotype-phenotype map is not
      sufficient to cause epistasis. Finally, it is shown that there exist correlations
      among the additive and epistatic effects among pairs of loci, caused by the
      inherent symmetries of Mendelian genetic systems. For instance, it is shown that
      a mutation that has a larger than average additive effect will tend to decrease
      the additive effect of a second mutation, i.e., it will tend to have a negative
      (canalizing) interaction with a subsequent gene substitution. This is confirmed
      in a preliminary analysis of QTL-data for adult body weight in mice.

PMID- 9766966
TI  - Requisite mutational load, pathway epistasis and deterministic mutation
      accumulation in sexual versus asexual populations.
AB  - A measure of the equilibrium load of deleterious mutations is developed that
      explicitly incorporates the level of genome-wide linkage disequilibrium. This
      measure, called the requisite mutational load, is based on the minimal net
      reproductive rate of the least mutated class necessary to prevent the
      deterministic mutation accumulation. If this minimal net reproductive rate is
      larger than ecological or physiological constraints allow, then: a) the
      population is driven to extinction via deterministic mutation accumulation, or b)
      a mutational Red-Queen ensues with adaptation counterbalancing mutation
      accumulation. Two population parameters determine the requisite mutational load:
      a) the equilibrium strength of selection, measured as a selection gradient, and
      b) the equilibrium opportunity for selection, measured as the variance in number
      of mutations per genome. The opportunity for selection is decomposed into the
      accumulation of mutations (average number per genome) and the level of genome
      wide linkage disequilibrium. Recombination can substantially reduce the requisite
      mutational load, compared to clonal reproduction, when there is buffering and/or
      reinforcing epistasis and also when there is positive assortative mating for
      fitness. Recombination is advantageous because it reduces the negative (variance
      reducing) linkage disequilibrium induced by beneficial epistasis. The functional
      form of the expression for requisite mutational load illustrates why epistasis
      within pathways, i.e., among closely interacting genes, is a powerful alternative
      to genome-wide truncation selection, as a means of reducing mutational load.

PMID- 9766967
TI  - Identification of four alternatively spliced isoforms of chicken casein kinase I
      alpha that are all expressed in diverse cell types.
AB  - Casein kinase I (CKI) is a family of widely expressed protein kinases. It is
      previously shown in mammalian tissues that CKIalpha exists as two or three
      alternatively spliced isoforms (Rowles et al.,1991; Zhang et al., 1996; Kuret et
      al., 1997). We now report that four alternatively spliced isoforms of CKIalpha
      are expressed in many chicken cells and tissues. A partial cDNA clone was
      isolated from a chicken brain library, using a probe derived from a bovine
      CKIalpha cDNA. The translated sequence of this clone was 100% identical to the
      bovine homolog containing the 'L' insert, with the addition of 12 amino acids
      just before the C terminus that had previously been reported in human and Xenopus
      CKIalpa. After completing the missing portion of the coding sequence by 5' RACE
      (rapid amplification of cDNA ends), full-length cDNA was PCR amplified from
      chicken brain cDNA, yielding four different products. These were cloned and
      sequenced and found to correspond to the four CKIalpha isoforms: CKIalpha,
      CKIalphaL, CKIalphaS and CKILalphaLS, where 'S' is the insert consisting of the
      12 human/Xenopus C-terminal amino acids. Using reverse transcription and
      polymerase chain reaction (Rt-PCR), it was shown that the four isoforms are all
      expressed in neurons, fibroblasts and several tissues. This represents the first
      demonstration that four splice variants exist and are all expressed in a single
      type of cell.

PMID- 9766968
TI  - Inducible expression of green fluorescent protein within channel catfish cells by
      a cecropin gene promoter.
AB  - The activity of an insect promoter of the cecropin B gene (Cec B) was
      investigated using green fluorescent protein (gfp) as a reporter in cells of
      channel catfish (Ictalurus punctatus). The expression vector pQZ-1 containing the
      Cec B promoter and a modified gfp cDNA sequence was delivered by lipofection to
      three catfish types: fibroblast and leukocyte cell lines, and primary cultures of
      leukocytes. No resistance genes were included in the vector for selection of GFP
      expressing cells. The GFP mRNA was detected in all three cell types with 5 to 10
      times higher concentrations observed in leukocytes than in fibroblasts.
      Expression was enhanced with the addition of irradiated Flavobacterium columnare
      (7.0 ?10(6) cells/ml) or Escherichia coli LPS (125microgram/ml). Quantitative RT
      PCR showed GFP mRNA reached maximum levels 24h after bacterial challenge in
      fibroblast cells, and at 10-12h after LPS challenge in fibroblasts and
      leukocytes. The number of fibroblasts expressing GFP increased by 0.8%, and the
      average of green fluorescence intensity increased by 52.8%, whereas the increase
      in leukocytes was 0.13% in cell number and 3.4% in fluorescence intensity. These
      results suggest that the transcription of the Cec B promoter in channel catfish
      cells exhibited an inducible pattern and could be placed under the control of the
      immune system (in vivo). The mechanisms for endogenous activation of the Cec B
      promoter and for production of gfp RNA in unchallenged cells remain to be
      studied.

PMID- 9766969
TI  - International Society for Pediatric and Adolescent Diabetes 24th annual meeting.
      Zurich, Switzerland, September 14-17, 1998. Abstracts.

PMID- 9766971
TI  - Proceedings of an International Conference on Dehydration, Rehydration and
      Exercise in the Heat. Nottingham, England, November 1-5, 1995.

PMID- 9766970
TI  - Very early thrombolysis in acute myocardial infarction and pulmonary embolism
      disease. Symposium proceedings. Ravenna, Italy, April 1996.

PMID- 9766972
TI  - A retrospective study of promethazine and its failure to produce the expected
      incidence of sedation during space flight.
AB  - Since March 1989, intramuscular (IM) promethazine has been successfully used to
      treat the symptoms of space motion sickness. The incidence of sedation associated
      with promethazine administration on the ground is large and may result in
      operational impact. The authors undertook a retrospective study to quantify the
      incidence of sedation from promethazine use during Space Shuttle flights. Crew
      medical debriefings from 14 shuttle missions were reviewed for crew members who
      had been treated with IM promethazine and their corresponding symptoms were
      identified. Twenty-one crew members received IM promethazine (25-50 mg), and only
      one experienced any associated sedation with no operational impact. This sedation
      incidence of less that 5% is in stark contrast to the 60 to 73% incidence of
      sedation seen in ground-based studies. The incidence of sedation during space
      flight from IM promethazine is substantially less than that seen on the ground
      and does not present an operational problem during Space Shuttle flights. Future
      investigations of environmental stressors and pharmacodynamic changes associated
      with space flight may explain the huge disparity between the space-flight and
      ground-based data.

PMID- 9766973
TI  - Gammaherpesvirus sequence comparisons.

PMID- 9766974
TI  - Functional interaction of human immunodeficiency virus type 1 Vpu and Gag with a
      novel member of the tetratricopeptide repeat protein family.

PMID- 9766975
TI  - Murine leukemia virus envelope protein in transgenic-mouse serum blocks infection
      in vitro.

PMID- 9766976
TI  - [Oncological lymph node sampling in lung cancer].

PMID- 9766977
TI  - The effects of a continuing medical education programme in interpersonal
      communication skills on doctor practice and patient satisfaction in Trinidad and
      Tobago.
AB  - This study investigates the effects of a brief training programme on the
      communication skills of doctors in ambulatory care settings in Trinidad and
      Tobago. Evaluation of doctor performance is based on analysis of audiotapes of
      doctors with their patients during routine clinic visits and on patient
      satisfaction ratings. A pre-test/post-test quasi-experimental study design was
      used to evaluate the effects of exposure to the training programme. Doctors were
      assigned to groups based on voluntary participation in the programme. Audiotapes
      of the 15 participating doctors (nine trained and six control) with 75 patients
      at baseline and 71 patients at the post-training assessment were used in this
      analysis. The audiotapes were content-coded using the Roter Interaction Analysis
      System (RIAS). Doctors trained in communication skills used significantly more
      target skills post-training than their untrained colleagues. Trained doctors used
      more facilitations in their visits and more open-ended questions than other
      doctors. There was also a trend towards more emotional talk, and more close-ended
      questions. Patients of trained doctors talked more overall, gave more information
      to their doctors and tended to use more positive talk compared to other patients.
      Trained doctors were judged as sounding more interested and friendly, while
      patients of trained doctors were judged as sounding more dominant, responsive and
      friendly than patients of untrained doctors. Consistent with these communication
      differences, patient satisfaction tended to be higher in visits of trained
      doctors.

PMID- 9766978
TI  - Effect of diuretics on sodium and chloride permeability in the rat papillary
      collecting duct.
AB  - While in vivo data suggests that diuretics such as furosemide and
      hydrochlorothiazide alter inner medulla collecting duct (IMCD) cell electrolyte
      transport, this has not been confirmed by in vivo studies nor have the mechanisms
      been evaluated. This study evaluated the direct effect of these diuretics as well
      as amiloride on sodium and chloride unidirectional permeability in the isolated
      perfused rat IMCD. In the absence of diuretics, the permeability of sodium was
      lower than that of chloride (0.63 +/- 0.05 compared with 0.83 +/- 0.08
      micrometer/s), although both were relatively impermeable when compared to water.
      Furosemide (10(-4)) and hydrochlorothiazide (10(-3)) both increased the
      diffusional permeability of chloride by approximately 30% (0.80 +/- 0.06 to 1.04
      +/- 0.09 micrometer/s, p < 0.01, and 0.74 +/- 0.09 to 0.98 +/- 0.10 micrometer/s,
      p < 0.02, respectively). However, sodium permeability was unaltered. Inhibition
      of Na+, K+-ATPase by ouabain or cooling (4 degrees C) inhibited basal sodium but
      not chloride permeability while a maximal antidiuretic AVP concentration did not
      alter sodium or chloride permeability. However, increasing the lumen and bath
      sodium chloride concentration from 150 to 300 and 600 mM significantly increased
      both sodium and particularly chloride conductance. In contrast, amiloride (10(
      4)) significantly reduced both sodium and chloride permeability. These studies
      support a direct effect of furosemide and hydrochlorothiazide on the IMCD and
      suggest that their in vivo effect is primarily mediated by facilitating the
      passive movement of chloride into the lumen via a favourable electrochemical
      gradient. These results also demonstrate that amiloride inhibits both sodium and
      chloride unidirectional permeability by mechanisms separate to that of the
      sulphonamide-related diuretics.

PMID- 9766979
TI  - Nonoccupational exposure to chrysotile asbestos and the risk of lung cancer.

PMID- 9766980
TI  - Nonoccupational exposure to chrysotile asbestos and the risk of lung cancer.

PMID- 9766981
TI  - Nonoccupational exposure to chrysotile asbestos and the risk of lung cancer.

PMID- 9766982
TI  - Nonoccupational exposure to chrysotile asbestos and the risk of lung cancer.

PMID- 9766983
TI  - Nonoccupational exposure to chrysotile asbestos and the risk of lung cancer.

PMID- 9766984
TI  - Endometriosis in the thoracic aorta.

PMID- 9766985
TI  - Dialysis therapy.

PMID- 9766986
TI  - Dialysis therapy.

PMID- 9766987
TI  - Dialysis therapy.

PMID- 9766988
TI  - Dialysis therapy.

PMID- 9766989
TI  - More on acid-base disorders.

PMID- 9766990
TI  - The rewards of reading instructions from journal editors.

PMID- 9766991
TI  - Nonoccupational exposure to chrysotile asbestos and the risk of lung cancer.

PMID- 9766992
TI  - Nonoccupational exposure to chrysotile asbestos and the risk of lung cancer.

PMID- 9766993
TI  - Antituberculosis-drug resistance.

PMID- 9766994
TI  - Antituberculosis-drug resistance.

PMID- 9766995
TI  - Antituberculosis-drug resistance.

PMID- 9766996
TI  - Augmented post-induction therapy in childhood lymphoblastic leukemia.

PMID- 9766997
TI  - Acute diverticulitis.

PMID- 9766998
TI  - Acute diverticulitis.

PMID- 9766999
TI  - Acute diverticulitis.

PMID- 9767000
TI  - Acute diverticulitis.

PMID- 9767001
TI  - Cardiovascular risk factors and atherosclerosis in children and young adults.

PMID- 9767002
TI  - Diagnosis of pulmonary embolism.

PMID- 9767003
TI  - Diagnosis of pulmonary embolism.

PMID- 9767004
TI  - Diagnosis of pulmonary embolism.

PMID- 9767005
TI  - Diagnosis of pulmonary embolism.

PMID- 9767007
TI  - Laboratory Behavioral Studies of Vulnerability to Drug Abuse. Proceedings of a
      meeting. August 2-3, 1994.

PMID- 9767006
TI  - Inhibition of the adherence of P-fimbriated Escherichia coli to uroepithelial
      cell surfaces by proanthocyanidin extracts from cranberries.

PMID- 9767008
TI  - Problems of drug dependence 1997: proceedings of the 59th annual scientific
      meeting.

PMID- 9767009
TI  - Correction. CTL induction by a tumour-associated antigen octapeptide derived from
      a murine lung carcinoma.

PMID- 9767010
TI  - Retracted correction. CTL induction by a tumour-associated antigen octapeptide
      derived from a murine lung carcinoma.

PMID- 9767011
TI  - Future perfect.

PMID- 9767012
TI  - A multidisciplinary approach to palliative transfusions at home.

PMID- 9767013
TI  - Cleaning up our practice.

PMID- 9767014
TI  - Electronic publishing can bring your work to life. Augmenting content with
      multimedia highlights and links.

PMID- 9767015
TI  - Cattle diet linked to bacterial growth.

PMID- 9767016
TI  - Senate Committee votes boost for NIH.

PMID- 9767017
TI  - RNA-splicing machinery revealed.

PMID- 9767018
TI  - Leptin sparks blood vessel growth.

PMID- 9767019
TI  - Transfer of Protein Data Bank sparks concern.

PMID- 9767020
TI  - Five researchers die in plane crash.

PMID- 9767021
TI  - The cerebellum: the brain's engine of agility.

PMID- 9767022
TI  - Multiplying knowledge of cell division, plant growth.

PMID- 9767023
TI  - Quiescence in nuclear transfer.

PMID- 9767024
TI  - The future of long life.

PMID- 9767025
TI  - The future of long life.

PMID- 9767026
TI  - The future of long life.

PMID- 9767027
TI  - The paradox of lead poisoning prevention.

PMID- 9767028
TI  - Reward for persistence in substance P research.

PMID- 9767031
TI  - Raising the stakes in the race for new malaria drugs.

PMID- 9767029
TI  - Routing MAP kinase cascades.

PMID- 9767032
TI  - Semiconductor beacons light up cell structures.

PMID- 9767033
TI  - Lasker Awards go to cancer researchers.

PMID- 9767034
TI  - A biomolecule building block from vents.

PMID- 9767035
TI  - Two more scientists died in Swissair crash.

PMID- 9767036
TI  - Fly development genes lead to immune find.

PMID- 9767037
TI  - Protecting medicine in the 21st century.

PMID- 9767038
TI  - A revolution in evolution.

PMID- 9767039
TI  - Cleaning CJD-contaminated instruments.

PMID- 9767040
TI  - Salt wars.

PMID- 9767041
TI  - Salt wars.

PMID- 9767042
TI  - Salt wars.

PMID- 9767043
TI  - Salt wars.

PMID- 9767044
TI  - Salt wars.

PMID- 9767045
TI  - Salt wars.

PMID- 9767046
TI  - Crystallography of a photocycle intermediate.

PMID- 9767047
TI  - The saturation debate.

PMID- 9767048
TI  - The evolution of sex.

PMID- 9767049
TI  - Why sex? Putting theory to the test.

PMID- 9767050
TI  - A new look at monogamy.

PMID- 9767051
TI  - A genomic battle of the sexes.

PMID- 9767052
TI  - [Resection margins after lumpectomy (tumorectomy) and much more].

PMID- 9767053
TI  - Mechanisms of cartilage destruction: onset of osteoarthritis research in Germany.
      Kloster Seeon, February 27-28, 1998. Abstracts.

PMID- 9767054
TI  - Proceedings of the annual meeting on Anesthesia and the Geriatric Patient. Gent,
      November 28-29, 1997.

PMID- 9767055
TI  - Photo quiz. Iron deficiency anemia: What's the cause?

PMID- 9767058
TI  - Prostatitis.
AB  - The laboratory diagnosis of acute bacterial prostatitis is straightforward and
      easily accomplished in clinical laboratories. Chronic bacterial prostatitis, and
      especially chronic idiopathic prostatitis (most often referred to as abacterial
      prostatitis), presents a real challenge to the clinician and clinical
      microbiologist. Clinically, the diagnosis of chronic idiopathic prostatitis is
      differentiated from that of acute prostatitis by a lack of prostatic inflammation
      and no "significant" (controversial) leukocytes or bacteria in the expressed
      prostatic secretions. Despite these diagnostic criteria, the etiology of chronic
      idiopathic prostatitis is unknown. While this review covers the entire spectrum
      of microbially caused acute prostatitis (including common and uncommon bacteria,
      viruses, fungi, and parasites) and microbially associated chronic prostatitis, a
      special focus has been given to chronic idiopathic prostatitis. The idiopathic
      syndrome is commonly diagnosed in men but is poorly treated. Recent data
      convincingly suggests a possible bacterial etiology for the condition.
      Provocative molecular studies have been published reporting the presence of 16S
      rRNA bacterial sequences in prostate biopsy tissue that is negative for ordinary
      bacteria by routine culture in men with chronic idiopathic prostatitis.
      Additionally, special culture methods have indicated that difficult-to-culture
      coryneforms and coagulase-negative staphylococci are present in expressed
      prostatic secretions found to be negative by routine culture techniques.
      Treatment failures are not uncommon in chronic prostatitis. Literature reports
      suggest that antimicrobial treatment failures in chronic idiopathic prostatitis
      caused by organisms producing extracellular slime might result from the virulent
      properties of coagulase-negative staphylococci or other bacteria. While it is
      difficult to definitively extrapolate from animal models, antibiotic
      pharmokinetic studies with a murine model have suggested that treatment failures
      in chronic prostatitis are probably a result of the local microenvironment
      surrounding the persistent focal and well-protected small bacterial biofilms
      buried within the prostate gland. These conclusions support the molecular and
      culture data implicating bacteria as a cause of chronic idiopathic prostatitis.

PMID- 9767056
TI  - Regulation and function of T-cell-mediated immunity during Toxoplasma gondii
      infection.
AB  - The intracellular protozoan Toxoplasma gondii is a widespread opportunistic
      parasite of humans and animals. Normally, T. gondii establishes itself within
      brain and skeletal muscle tissues, persisting for the life of the host.
      Initiating and sustaining strong T-cell-mediated immunity is crucial in
      preventing the emergence of T. gondii as a serious pathogen. The parasite induces
      high levels of gamma interferon (IFN-gamma) during initial infection as a result
      of early T-cell as well as natural killer (NK) cell activation. Induction of
      interleukin-12 by macrophages is a major mechanism driving early IFN-gamma
      synthesis. The latter cytokine, in addition to promoting the differentiation of
      Th1 effectors, is important in macrophage activation and acquisition of
      microbicidal functions, such as nitric oxide release. During chronic infection,
      parasite-specific T lymphocytes release high levels of IFN-gamma, which is
      required to prevent cyst reactivation. T-cell-mediated cytolytic activity against
      infected cells, while easily demonstrable, plays a secondary role to inflammatory
      cytokine production. While part of the clinical manifestations of toxoplasmosis
      results from direct tissue destruction by the parasite, inflammatory cytokine
      mediated immunopathologic changes may also contribute to disease progression.

PMID- 9767059
TI  - Protease inhibitors as antiviral agents.
AB  - Currently, there are a number of approved antiviral agents for use in the
      treatment of viral infections. However, many instances exist in which the use of
      a second antiviral agent would be beneficial because it would allow the option of
      either an alternative or a combination therapeutic approach. Accordingly, virus
      encoded proteases have emerged as new targets for antiviral intervention.
      Molecular studies have indicated that viral proteases play a critical role in the
      life cycle of many viruses by effecting the cleavage of high-molecular-weight
      viral polyprotein precursors to yield functional products or by catalyzing the
      processing of the structural proteins necessary for assembly and morphogenesis of
      virus particles. This review summarizes some of the important general features of
      virus-encoded proteases and highlights new advances and/or specific challenges
      that are associated with the research and development of viral protease
      inhibitors. Specifically, the viral proteases encoded by the herpesvirus,
      retrovirus, hepatitis C virus, and human rhinovirus families are discussed.

PMID- 9767057
TI  - Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods,
      and pathogenicity factors.
AB  - Bacteria belonging to the genus Klebsiella frequently cause human nosocomial
      infections. In particular, the medically most important Klebsiella species,
      Klebsiella pneumoniae, accounts for a significant proportion of hospital-acquired
      urinary tract infections, pneumonia, septicemias, and soft tissue infections. The
      principal pathogenic reservoirs for transmission of Klebsiella are the
      gastrointestinal tract and the hands of hospital personnel. Because of their
      ability to spread rapidly in the hospital environment, these bacteria tend to
      cause nosocomial outbreaks. Hospital outbreaks of multidrug-resistant Klebsiella
      spp., especially those in neonatal wards, are often caused by new types of
      strains, the so-called extended-spectrum-beta-lactamase (ESBL) producers. The
      incidence of ESBL-producing strains among clinical Klebsiella isolates has been
      steadily increasing over the past years. The resulting limitations on the
      therapeutic options demand new measures for the management of Klebsiella hospital
      infections. While the different typing methods are useful epidemiological tools
      for infection control, recent findings about Klebsiella virulence factors have
      provided new insights into the pathogenic strategies of these bacteria.
      Klebsiella pathogenicity factors such as capsules or lipopolysaccharides are
      presently considered to be promising candidates for vaccination efforts that may
      serve as immunological infection control measures.

PMID- 9767062
TI  - Pain assessment and evaluation of patients who have neuropathic pain.
AB  - Pain assessment and physical examination are the first crucial steps in diagnosis
      of neuropathic pain disorders because these are still solely diagnosed on
      clinical grounds. The physical examination should be conducted in such a way that
      all of the positive sensory phenomena, such as allodynia, hyperalgesia,
      hyperpathia, summation, and after-sensation are elicited. Other physical
      examination findings should corroborate the diagnostic impression of neuropathic
      pain. Specific pain diagnosis should then lead to more specific therapy.

PMID- 9767063
TI  - Painful polyneuropathy.
AB  - Painful polyneuropathy is one of the most common chronic pain syndromes
      neurologists are asked to assess for diagnostic and therapeutic purposes. This
      article reviews the most current clinical guidelines, including history, pain
      assessment, physical examination findings, treatment recommendations, and
      pathophysiologic pain mechanisms underlying this condition. As a result of recent
      advances, the understanding and therapy of pain associated with polyneuropathy
      has evolved over the past several years and will continue to do so in the years
      to come.

PMID- 9767064
TI  - Pain caused by herpes zoster infection.
AB  - Postherpetic neuralgia (PHN) is a neuropathic pain disorder that occurs most
      often in the elderly. This painful condition is uniquely suited for clinical
      research, resulting in an emerging understanding of the pathophysiology of the
      persistent pain. Until recently, only the tricyclic antidepressants proved
      effective for PHN. Controlled trials of a wide variety of therapeutic strategies
      are in progress or have been recently completed.

PMID- 9767065
TI  - Spinal and radicular pain disorders.
AB  - Although most acute conditions of the spine are benign and self-limited, the
      economic costs and disability resulting from these disorders have reached
      epidemic proportions in industrialized society. Recent scientific research to
      determine the causes of common spinal disorders, long attributed to structural
      abnormalities, have now implicated complex biochemical and neurophysiologic
      processes which may offer insights for future therapy interventions. This article
      reviews the functional and pathologic anatomy and correlates with current
      diagnostic and nonoperative management strategies for common mechanical spinal
      and radicular pain syndromes.

PMID- 9767060
TI  - Management of infections due to antibiotic-resistant Streptococcus pneumoniae.
AB  - Antibiotic-resistant strains of Streptococcus pneumoniae are becoming more
      prevalent throughout the world; this has resulted in modifications of treatment
      approaches. Management of bacterial meningitis has the greatest consensus.
      Strategies for treating other systemic infections such as pneumonia, bacteremia,
      and musculoskeletal infections are evolving, in part related to the availability
      of new antibiotics which are active in vitro against isolates resistant to
      penicillin and the extended-spectrum cephalosporins. However, there are currently
      very limited data related to the clinical efficacy of these new agents. The
      studies upon which current recommendations are based are reviewed. Otitis media
      represents the single most common infection due to S. pneumoniae. Recommendations
      for treatment of acute otitis media due to drug-resistant strains and the
      rationale for these recommendations are discussed.

PMID- 9767066
TI  - Traumatic neuralgias: complex regional pain syndromes (reflex sympathetic
      dystrophy and causalgia): clinical characteristics, pathophysiological mechanisms
      and therapy.
AB  - Complex regional pain syndromes (CPRS) may develop as a disproportionate
      consequence of a trauma affecting the limbs without (CRPS I, reflex sympathetic
      dystrophy) or with (CRPS II, causalgia) obvious nerve lesions. The clinical
      picture of CRPS consists of asymmetrical distal extremity pain, swelling, and
      autonomic (sympathetic) and motor symptoms. Changes in the peripheral and central
      somatosensory, autonomic and motor processing, and a pathologic interaction of
      sympathetic and afferent systems are discussed as underlying pathophysiologic
      mechanisms. Therapeutic strategies include pharmacologic pain relief,
      sympatholytic interventions, and rehabilitation.

PMID- 9767067
TI  - Neuropathic pain in the cancer patient.
AB  - Cancer presents itself in numerous ways, adding to the complexity of any pain
      syndrome with which it is associated. Neuropathic pain, unlike many other pain
      syndromes, is difficult to treat even in the absence of cancer. The combination
      results in a heterogeneous group of patients with a complex set of symptoms. This
      makes the assessment of pain, classification of syndromes, and clinical study a
      challenge. If the disease is nonprogressive, general principles of care are
      essentially the same as in those without cancer. In patients with progressive
      disease and more refractory painful conditions, spinal anesthetic and
      neurosurgical therapies must often be considered. Under such circumstances,
      caregivers are forced to carefully balance uncertain benefits and risks, often
      without the luxury of time. More careful observation and controlled trials in
      these patients help facilitate this challenging process.

PMID- 9767061
TI  - Pneumococcal diversity: considerations for new vaccine strategies with emphasis
      on pneumococcal surface protein A (PspA).
AB  - Streptococcus pneumoniae is a problematic infectious agent, whose seriousness to
      human health has been underscored by the recent rise in the frequency of
      isolation of multidrug-resistant strains. Pneumococcal pneumonia in the elderly
      is common and often fatal. Young children in the developing world are at
      significant risk for fatal pneumococcal respiratory disease, while in the
      developed world otitis media in children results in substantial economic costs.
      Immunocompromised patients are extremely susceptible to pneumococcal infection.
      With 90 different capsular types thus far described, the diversity of pneumococci
      contributes to the challenges of preventing and treating S. pneumoniae
      infections. The current capsular polysaccharide vaccine is not recommended for
      use in children younger than 2 years and is not fully effective in the elderly.
      Therefore, innovative vaccine strategies to protect against this agent are
      needed. Given the immunogenic nature of S. pneumoniae proteins, these molecules
      are being investigated as potential vaccine candidates. Pneumococcal surface
      protein A (PspA) has been evaluated for its ability to elicit protection against
      S. pneumoniae infection in mouse models of systemic and local disease. This
      review focuses on immune system responsiveness to PspA and the ability of PspA to
      elicit cross-protection against heterologous strains. These parameters will be
      critical to the design of broadly protective pneumococcal vaccines.

PMID- 9767069
TI  - Central pain and dysesthesia syndrome.
AB  - This article presents recent observations about different recognized central pain
      syndromes (CPS) and discusses them in light of contemporary microelectrode and
      imaging findings. Different theories regarding the generation of CPS are
      reviewed, with an emphasis on difficulties in diagnosis and treatment. The author
      discourages destructive procedures for treatment of CPS, favoring, instead,
      reversible procedures such as stimulation techniques and drug delivery systems.

PMID- 9767068
TI  - Pain in central and peripheral demyelinating disorders.
AB  - Moderate to severe pain is a common feature of central and peripheral
      demyelinating disorders. Pain in multiple sclerosis tends to occur when the
      disease is well-established and usually lingers infinitely. Pain in Guillain
      Barre syndrome tends to be particularly severe at the time of initial
      presentation and usually resolves over 8 to 12 weeks. Pain in both conditions is
      generally caused by either the direct effects of nerve injury or the result of
      paralysis and prolonged immobilization. Pain syndromes are well-defined in each
      disorder based on the underlying pathophysiology. Treatment involves a variety of
      pharmacologic and nonpharmacologic approaches individualized for each specific
      pain syndrome.

PMID- 9767071
TI  - New developments in rehabilitation of neuropathic pain syndromes.
AB  - The common medical treatments of neuropathic pain, medication and nerve blocks,
      are often only partially effective in providing significant and long-term pain
      relief. Patients suffering chronic pain often fall prey to associated emotional
      suffering, functional impairment, and difficulties in multiple areas of their
      lives, including family disruption, social withdrawal, and vocational disability.
      An interdisciplinary approach to pain management draws on the skills of physical
      and occupational therapists, pain psychologists, biofeedback specialists, and
      vocational counselors. It focuses on both pain management and functional
      restoration, and should be considered standard treatment for chronically painful
      conditions. Interdisciplinary pain management views the patient as an active
      agent, responsible for learning and applying self-management techniques for
      controlling pain, with the staff assuming a teaching and consulting role.
      Although much more labor intensive, interdisciplinary pain management is more
      effective over time in managing chronic pain, in preventing unnecessary emotional
      and physical impairment, and in controlling overall medical costs.

PMID- 9767070
TI  - Phantom limb pain and related disorders.
AB  - Postamputation phenomena, including painful and nonpainful phantom sensations
      occur following loss of limbs and other body parts. Peripheral and central
      nervous system mechanisms play a role in persistent phantom pain. Understanding
      the pathophysiology of this syndrome has improved in recent years. Comprehensive
      evaluation and a multimodality treatment approach comprise the current standard
      of care of the patient with phantom pain.

PMID- 9767072
TI  - Recent advances in the pharmacology of nerve-injury pain.
AB  - Nerve injury pain remains a complex clinical challenge. Although the development
      of animal models of nerve injury pain has aided our understanding of potential
      pathophysiologic mechanisms for this condition, effective treatment still remains
      beyond our reach. Several classes of agents appear to block pain behavior in
      these animal models and humans, but they are often limited in their use by low
      efficacy, or undesirable side-effects. A prerequisite for the improvement of
      nerve injury pain includes the development of clinically-relevant animal models
      in which therapeutic targets can be identified.

PMID- 9767074
TI  - Simultaneous analysis of multiple gene expression patterns as a function of
      development, injury or senescence.
AB  - Concurrent changes in expression of eight genes were examined following cryogenic
      rat brain injury. Cortical RNA levels were catalogued at time 0, and at 1 h and 1
      week following injury. The genes include thymidine kinase (TK), c-fos, renin,
      myelin basic protein (MBP), proteolipid protein (PLP), glial fibrillary acidic
      protein (GFAP), insulin-like growth factor-1 (IGF-1), and somatostatin. All
      demonstrate increased expression following injury. Renin and c-fos exhibit
      detectable changes as early as 1 h post-injury.

PMID- 9767073
TI  - Oxidation of NADH by intact segments of soybean hypocotyls and stimulation by 2,4
      D.
AB  - Intact sections of soybean cut from regions of cell elongation of hypocotyls of
      etiolated soybean seedlings oxidized externally supplied NADH (NADH is an
      impermeant substrate). The oxidation of NADH by 1-cm intact sections was
      stimulated by the plant growth factor 2,4-dichlorophenoxyacetic acid (2,4-D). The
      optimum concentration of 2,4-D for stimulation was about 1 microM. Stimulations
      also were given by the naturally occurring 2,4-D analog, indole-3-acetic acid
      (IAA), but not by the growth inactive 2,4-D analog 2,3-dichlorophenoxyacetic acid
      (2,3-D). The findings confirm studies comparing inside-out and right side-out
      vesicles that show the 2,4-D-stimulated NADH oxidase to be located at the
      external cell surface. Since plant cells are unlikely to encounter NADH at their
      external cell surface, functions of the oxidase in reactions other than oxidation
      of NADH are discussed.

PMID- 9767075
TI  - Homeoboxes in plant development.
AB  - The homeobox is a 180 bp consensus DNA sequence present in a number of genes
      involved in developmental processes. This review focuses on the structure and
      function of plant homeobox genes and of the proteins they encode. Plant homeobox
      genes have been identified in studies using mutants, degenerate oligonucleotides
      deduced from conserved sequences, differential screening or binding to known
      promoters. According to sequence conservation, plant homeoboxes can be subdivided
      into different families, each comprising several members. Evolutionary studies
      indicate that the different families have diverged prior to the separation of the
      branches leading to animals, plants and fungi. Accordingly, members of different
      families show characteristic structural and functional properties. As an example,
      kn1-like genes seem to be involved in different aspects of the control of cell
      fate determination in the shoot meristem; HD-Zip genes, which encode proteins
      containing a leucine zipper motif adjacent to the homeodomain, are believed to
      operate at later stages of development; and gl2-like genes are involved in
      epidermal cell differentiation. Future studies should be oriented to discern the
      precise function of the many homeobox genes present in plant genomes, and to
      evaluate their use as modifiers of plant development.

PMID- 9767076
TI  - A new member of YER057c family in Trypanosoma cruzi is adjacent to an ABC
      transporter.
AB  - Tcp17 is a Trypanosoma cruzi gene located contiguous to the ABC-transporter
      tcpgp2. The protein contains 160 amino acid residues with a predicted molecular
      mass of 16.5kDa. Western blot analysis using a polyclonal antiserum against
      recombinant TCP17 revealed that the protein is only expressed in the epimastigote
      form of the parasite; we did not detect the protein either in the amastigote or
      trypomastigote forms. A sequence comparison of TCP17 showed a remarkable homology
      with a conserved family of prokaryotic and eukaryotic proteins called YER057c
      whose function has not yet been characterized. Here, we propose a new signature
      of this family considering the N-terminal: [IV]-X(4)-[AV]-[AP]-X-[AP]-X(3)-Y-X(9)
      [LIVF]-X(2)-[SA]-G-[QS], and the C-terminal: [AT]-R-X(2)-[IVFY]-X-[VC]-X(2)-L-P
      X(4)-[LIVM]-E-[IVM] -[DE] motifs. Immunofluorescence and immunoelectron
      microscopy studies suggest that the protein has a wide distribution in the cell,
      with a higher concentration in the external side of the plasma membrane, on the
      Golgi complex and on cytoplasmic vacuoles. Although the physiological function of
      TCP17 is unknown, its conservation in evolution suggests biological relevance in
      the parasite.

PMID- 9767077
TI  - Structure and expression of fatty acid desaturases.
AB  - Fatty acid desaturases are enzymes that introduce double bonds into fatty acyl
      chains. They are present in all groups of organisms, i.e., bacteria, fungi,
      plants and animals, and play a key role in the maintenance of the proper
      structure and functioning of biological membranes. The desaturases are
      characterized by the presence of three conserved histidine tracks which are
      presumed to compose the Fe-binding active centers of the enzymes. Recent findings
      on the structure and expression of different types of fatty acid desaturase in
      cyanobacteria, plants and animals are reviewed in this article. Roles of
      individual desaturases in temperature acclimation and principles of regulation of
      the desaturase genes are discussed.

PMID- 9767078
TI  - Molecular regulators involved in vertebrate eye development.
AB  - Development of the eye can be subdivided into three phases. The first phase is
      the formation of the major structures of the eye by the processes of induction
      and regional specification. The second is the maturation of these structures to
      form the functional eye, and the third phase is the formation of neuronal
      connections between retina and the optic tectum. These processes are tightly
      regulated by signalling cascades that direct axonal outgrowth, cellular
      proliferation and differentiation. Some members of these signalling cascades have
      been identified in recent studies. These include secreted factors which transmit
      signals extracellularly, and receptors and transcription factors which are
      members of intracellular signalling pathways that respond to extracellular
      signals. This review summarizes the recent research that has implicated these
      factors in playing a role in eye development on the basis of functional or
      expression criteria.

PMID- 9767079
TI  - Effects of the loss of capacity for N-glycosylation on the transport activity and
      cellular localization of the human reduced folate carrier.
AB  - The role of N-glycosylation in reduced folate carrier (RFC) transport and
      membrane targeting was examined in transport-deficient K562 (K500E) cells
      transfected with human RFC cDNAs. Treatment of cells expressing wild-type RFC
      with tunicamycin (0-3 microg) resulted in a progressive shift of the
      approximately 85 kDa RFC on western blots to 65 kDa. At 3 microg/ml tunicamycin,
      the nearly complete loss of glycosylated RFC was accompanied by a approximately
      25% decreased rate of methotrexate uptake. A deglycosylated RFC cDNA construct in
      which asparagine-58 was replaced by glutamine (Gln58-RFC) was expressed in K500E
      cells as a 65 kDa protein and restored transport capacity for methotrexate and
      (6S)5-formyl tetrahydrofolate. With both wild-type and Gln58-RFC constructs,
      expression of cDNA-encoded RFC protein far exceeded relative levels of RFC
      uptake. Wild-type and Gln58-RFCs containing a hemagglutinin (HA) epitope at the
      carboxyl terminus were similarly functional and, by immunofluorescence staining
      with rhodamine-conjugated anti-HA antibody, were localized to plasma membranes.
      Collectively, our results demonstrate that N-glycosylation of human RFC plays no
      significant role in either transport function or membrane targeting. The
      discrepancy between the stoichiometries of RFC expression and transport activity
      for both wild-type RFC and Gln58-RFC implies that identical regulatory controls
      and/or non-RFC transport components are necessary to completely restore transport
      function in the transfected cells.

PMID- 9767080
TI  - Newborn rat brainstem preparation with the trigeminal nerve attached for pain
      study.
AB  - Studies using a brainstem-spinal cord preparation isolated from newborn rats have
      provided substantial information on neuro-physiology, -pharmacology and -anatomy
      of the respiratory center, such as mechanisms of respiratory rhythm generation,
      development of a respiratory center or respiratory reflex [T. Murakoshi, T.
      Suzue, S. Tamai, A pharmacological study on respiratory rhythm in the isolated
      brainstem-spinal cord preparation from newborn rat, Br. J. Pharmac. 86 (1985) 95
      104 [5]; H. Onimaru, A. Arata, I. Homma, Primary respiratory rhythm generator in
      the medulla of brainstem-spinal cord preparations from newborn rats, Brain Res.
      445 (1988) 314-324 [6]; H. Onimaru, I. Homma, Whole cell recordings from
      respiratory neurons in the medulla of brainstem-spinal cord preparations isolated
      from newborn rats, Pflugers Arch. 420 (1992) 399-406 [7]; J.C. Smith, K.
      Ballanyi, D.W. Richter, Whole-cell patch clamp recordings from respiratory
      neurons in neonatal rat brainstem in vitro, Neurosci. Lett. 314 (1992) 153-156
      [10]; T. Suzue, Respiratory rhythm generation in the in vitro brainstem-spinal
      cord preparation of the neonatal rat, J. Physiol. (London) 354 (1984) 173-183
      [11], reviewed in H. Onimaru, A. Arata, I. Homma, Neuronal mechanisms of
      respiratory rhythm generation: An approach using in vitro preparation, Jpn. J.
      Physiol. 47 (1997) 385-403 [8]]. Recently, the dissecting method of the
      preparation was modified to introduce a brainstem preparation with the trigeminal
      primary afferents attached for pain studies [M. Hamba, Repetitive stimulation
      potentiated the stimulus-evoked firing in the trigeminal caudalis-in vitro study.
      Neurosci. Res. 20 (1996) s163 [2]; M. Hamba, Stimulation-induced responses of the
      trigeminal caudal neurons in the brainstem preparation isolated from newborn
      rats, Brain Res. 785 (1998) 66-74 [3]]. As reported previously [3], the activity
      dependent change in the excitability of pain-processing neurons, wind-up
      phenomenon, was studied in the trigeminal caudalis by stimulating the mandibular
      nerve, using a modified brainstem preparation isolated from newborn rats. The
      caudalis, the medulla dorsal horn, is known as the center for processing pain and
      sensory information from the cranio-facial area. The results indicated that the
      brainstem preparation is applicable for studies on the neuroplasticity at the
      pain-processing synapses. Here, we describe the method for isolation of a
      brainstem preparation with the trigeminal mandibular nerve attached and for
      recording the synaptic response evoked in the caudal neurons, using a whole-cell
      patch clamp technique. In the present study, we demonstrated repetitive
      stimulation-induced responses of caudal neurons at postnatal day 1 as an example
      showing the feasibility of the preparation for pain studies.

PMID- 9767081
TI  - Determination of the depth of BODIPY probes in model membranes by parallax
      analysis of fluorescence quenching.
AB  - The location of a series of lipophilic and lipid-attached BODIPY (4, 4-difluoro-4
      bora-3a,4a-diaza-s-indacene) membrane probes was analyzed by the quenching of
      BODIPY fluorescence by a series of nitroxide-labeled lipids in which the depth of
      the nitroxide group is varied. When attached to the polar headgroup of PE the
      BODIPY remained near the polar headgroup in depth. However, when attached at the
      end of free or phospholipid-attached fatty acyl chains, or when attached to two
      hydrocarbon chains, we observed two probe populations. One, usually dominant,
      population of BODIPY groups 'looped back' towards the surface, but a second
      population remained deeply embedded within the bilayer. When attached to a fatty
      acid or fatty acyl chain, the deep population appeared to locate at a depth
      related to its point of attachment to the acyl chain. In BODIPY linked to free
      fatty acids, the location of the deep population responded to the ionization of
      the carboxyl group. Because, unlike NBD (7-nitro-2,1,3-benzoxadiazol-4-yl) and
      most dansyl groups, acyl chain linked BODIPY groups can exist in a deeply buried
      form we conclude that BODIPY linked acyl chains are superior to NBD or dansyl
      linked acyl chains as membrane probes.

PMID- 9767082
TI  - Characterization of the pectin methylesterase-like gene AtPME3: a new member of a
      gene family comprising at least 12 genes in Arabidopsis thaliana.
AB  - Pectin demethylesterification appears to be catalysed by a number of pectin
      methylesterase (PME) isoenzymes in higher plant species. In order to better
      define the biological role of these isoenzymes in plant cell growth and
      differentiation, we undertook molecular studies on the PME-encoding genes in
      Arabidopsis thaliana. In this paper, we report the characterization of AtPME3, a
      new PME-related gene of 4kb in length that we have mapped on Chromosome III.
      AtPME3 encodes a putative mature PME-related isoenzyme of 34kDa with a basic
      isoelectric point. Since the extent of the gene family encoding PME in higher
      plant species is still unknown, we resorted to the use of degenerate primers
      designed from several well-known consensus regions to identify new PME-related
      genes in the genome of Arabidopsis. Our results, in combination with several
      known expressed sequences tags (ESTs), indicate that the Arabidopsis genome
      contains at least 12 PME-related genes. Consequently, a method of systematic gene
      expression analysis has been applied in order to discern the expression pattern
      of these 12 genes throughout the plant at the floral stage. Whereas most of these
      genes appeared to be more or less ubiquitously expressed throughout the plant,
      several genes are distinguishable by their strikingly specific expression in
      certain organs. The present data bring a new insight into the role of specific
      PME-related genes in flower and root development.

PMID- 9767083
TI  - Laser-Doppler flowmetry utilizing a thinned skull cranial window preparation and
      automated stimulation.
AB  - For several decades, cranial windows have been used to investigate questions
      relating to cerebral blood flow and its regulation. In general, these techniques
      have utilized either 'open' cranial windows for the direct observation of the
      intracranial vasculature, or 'closed' cranial windows in which the skull and dura
      are removed and replaced with a clear seal, such as a coverslip. Here we describe
      a method of studying blood flow responses elicited by the physiological stimulus
      of whisker movement while using a 'thinned skull' cranial window created over the
      rat whisker-barrel cortex. This method employing an automated whisker stimulator
      coupled with laser-Doppler flowmetry focused through the thinned skull cranial
      window, is less invasive than other cranial window techniques, and allows for the
      study of the effects of stimulation parameters and systemically administered
      compounds on whisker movement elicited blood flow responses. Automated whisker
      stimulation and data collection also allow for precise temporal averaging of
      laser-Doppler measured responses, leading to increased precision in determining
      the true shape of the evoked blood flow response pattern.

PMID- 9767084
TI  - Distribution of 11-cis LRAT, 11-cis RD and 11-cis REH in bovine retinal pigment
      epithelium membranes.
AB  - Our recent finding of the co-localization of 11-cis retinyl esters and 11-cis
      retinyl ester hydrolase (11-cis REH) activity in bovine retinal pigment
      epithelium (RPE) plasma membrane (PM) has led us to explore the possibility that
      the PM may provide 11-cis retinal for rhodopsin regeneration. In the RPE, visual
      chromophore is synthesized via a membrane associated 11-cis retinol dehydrogenase
      (11-cis RD). Accordingly, bovine RPE membranes enriched with either endoplasmic
      reticulum (ER) or plasma membrane (PM) enzyme markers were prepared and assayed
      for visual cycle enzyme activities. Pronounced 11-cis RD activity was associated
      with both ER- and PM-enriched membrane fractions. In contrast, 11-cis REH
      activity was mostly recovered in PM-enriched fractions while LRAT activity was
      found only in ER-enriched membranes. The finding that both 11-cis retinol and 11
      cis retinal can be produced at the PM of the bovine RPE strongly suggests that 11
      cis retinyl esters at this subcellular locale serve as a precursor of visual
      chromophore for pigment regeneration.

PMID- 9767085
TI  - A constitutively activated mutant of galphaq down-regulates EP-cadherin
      expression and decreases adhesion between ectodermal cells at gastrulation.
AB  - We have examined the expression and function of the heterotrimeric GTP-binding
      protein Gq during early Xenopus embryogenesis. Abundant XGalphaq transcripts were
      detected in oocytes and early embryos by Northern blot analysis. In situ
      hybridization revealed that these transcripts are confined to the animal
      hemisphere of the mature oocyte and to the presumptive ectoderm of cleaving
      embryos. Microinjection at the two-cell stage of alphaq and Q209Lalphaq, a
      constitutively activated mutant, causes a disruption in ectodermal cell adhesion
      at late gastrulation. Dissociation/reaggregation experiments performed on animal
      cap explants clearly demonstrate that the Q209Lalphaq-induced phenotype occurs
      after reaggregation of the explants with a time-course similar to that observed
      in whole embryos. RT-PCR experiments performed on the explants from Q209Lalphaq
      injected embryos revealed a selective decrease in the amount of EP-cadherin mRNA.
      Co-injection of EP-cadherin RNA, but also E-cadherin RNA, rescued the
      disaggregated phenotype. These data emphasize the functional link between Gq
      protein-coupled signalling pathways and cadherin molecules in the ectodermal
      layer during the morphogenetic movements of gastrulation.

PMID- 9767086
TI  - Treatment with anti-transforming growth factor beta antibodies influences an
      altered pattern of cytokines gene expression in injured rat liver.
AB  - The role of transforming growth factor beta1 (TGF-beta1) in mediating hepatic
      inflammation and regeneration after acute liver injury is beginning to be
      elucidated, yet its in vivo effect on the gene expression of the major pro
      inflammatory and anti-inflammatory cytokines produced during that process is
      unknown. Our previous experiments demonstrated that anti-TGF-beta-treated animals
      presented profound histological changes as compared with control animals.
      Therefore, our hypothesis was that by blocking in vivo TGF-beta1 action, with
      polyclonal anti-TGF-beta antibodies, we could monitor by RT-PCR significative
      alterations on the gene expression of IL-1beta, IL-6, TGF-beta, TNF-alpha, IL-4
      and IL-10 in liver-regenerated rats after administration of a single CCl4 dosing.
      Accordingly, we here report a completely different pattern of cytokines gene
      expression amidst those groups of rats. Pro-inflammatory cytokines gene
      expression in control animals showed a clear-cut pattern peaking at 1-2 days
      postinjury and declining thereafter. Interestingly, IL-6 was present in the
      control animals only between 12 and 24 h after CCl4 dosing. In the experimental
      animals, TGF-beta1 was mainly increased at 4 and 6 days, while IL-6 mRNA was
      completely absent. IL-1beta mRNA expression was also altered in the experimental
      rats, albeit TNF-alpha was nearly unaffected. IL-4 was fully absent in control
      rats, but remarkably expressed in experimental animals throughout the study. IL
      10 was also more expressed in experimental animals.

PMID- 9767087
TI  - Neisseria gonorrhoeae contains multiple copies of a gene that may encode a site
      specific recombinase and is associated with DNA rearrangements.
AB  - A 960-bp ORF potentially encoding a site-specific recombinase has been cloned
      from Neisseria gonorrhoeae MS11-A. This ORF was designated pivNg on the basis of
      similarity of the deduced amino acid sequence to the Piv proteins of Moraxella
      spp. that are site-specific invertases. Southern hybridization and sequence
      analysis revealed that there were multiple copies of pivNg sequence within the
      genomes of N. gonorrhoeae strains tested, but not in several other neisserial
      species. Southern hybridization and sequence analysis further suggested that
      pivNg sequences may be associated with genomic rearrangements.

PMID- 9767088
TI  - Simultaneous isotopic and nonisotopic in situ hybridization histochemistry with
      cRNA probes.
AB  - In situ hybridization histochemistry is widely used to study gene expression at
      the mRNA level in tissues and cells. Double label in situ hybridization allows
      for coexpression studies. We describe a protocol for the simultaneous
      hybridization of two cRNA probes tagged with and digoxigenin-UTP, respectively,
      to frozen brain tissue sections. Hybridization signals of digoxigenin-tagged
      probes appear as purple cytoplasmic staining following detection of digoxigenin
      residues by an alkaline-phosphatase-(AP)-linked antibody. Signals resulting from
      hybridization of radiolabeled probes are detected as silver grains overlying
      cellular profiles in sections coated with autoradiographic emulsion. Grain
      counting allows for semiquantitatively estimates of the cellular expression
      levels of transcripts. Suitable cRNA-probes can be derived from linear templates
      generated by polymerase chain reaction (PCR) using nested primers which contain
      RNA-polymerase promotor sites. The cRNA-probes are sensitive and allow an
      application of this protocol to the detection of a wide range of mRNAs of medium
      or low abundance.

PMID- 9767089
TI  - Incorporation of extracellular phospholipids and their effect on the growth and
      lipid metabolism of the Saccharomyces cerevisiae cho1/pss mutant.
AB  - The cho1/pss mutant of Saccharomyces cerevisiae, which is auxotrophic for choline
      or ethanolamine because of the deficiency in phosphatidylserine synthesis, grew
      in the presence of 0.05 mM phosphatidylcholine (PC) with octanoic acids (diC8PC)
      or decanoic acids (diC10PC), but not in the presence of PC with longer acyl
      residues. It did not grow in the presence of the soluble hydrolytic products of
      PC, phosphorylcholine or glycerophosphorylcholine, at comparable concentrations.
      Addition of 10 mM hemicholinium-3, a choline transport inhibitor, or disruption
      of the CTR gene, which encodes a choline transporter, inhibited the growth of the
      cho1/pss mutant in the presence of choline, but not in the presence of 0.1 mM
      diC8PC. Under diC8PC-supported growth conditions, octanoic acid was barely
      detectable in the cellular phospholipid fraction, but was recovered in the
      culture medium as the free acid, and the phosphatidylethanolamine (PE) content
      was low in comparison to the choline-supported conditions. These results suggest
      that PCs with short acyl residues were taken up by the cho1/pss mutant and
      remodeled as they were used, and that PCs with short acyl residues do not inhibit
      conversion of PE to PC. The current results provide a new direction in the
      analysis of intracellular phospholipid movement and metabolism in yeast.

PMID- 9767090
TI  - Ultrastructural characterization of cationic liposome-DNA complexes showing
      enhanced stability in serum and high transfection activity in vivo.
AB  - We have investigated the morphology and transfection activity of cationic
      liposome-DNA complexes (CLDC) under conditions relevant to both in vivo and in
      vitro studies. Moreover we have attempted to establish structure-function
      relationships relevant for high transfection activities under both conditions.
      CLDC were composed of dimethyldioctadecylammonium bromide with either 1, 2
      dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or cholesterol (Chol)
      interacting either with pre-condensed DNA or with uncondensed plasmid DNA.
      Furthermore for steric stabilization 1% poly(ethylene glycol)-phospholipid
      conjugate was added to CLDC containing Chol and plasmid DNA. The in vivo studies
      were carried out in mice following i.v. injection, and the in vitro studies were
      performed on SK-BR-3 human breast cancer cells in the presence of media with
      serum. The morphology of the CLDC, monitored by freeze-fracture electron
      microscopy, was investigated after mixing with mouse serum or the medium where
      the cells were kept. The substitution of DOPE with Chol, and the addition of N
      [omega-methoxypoly(oxyethylene)-alpha-oxycarbonyl-DSPE+ ++ are producing CLDC
      which are stabilized with respect to time and serum, and are relatively small
      (100-300 nm). These stabilized complexes show high expression of a marker gene in
      mouse lungs reaching expression values up to 10 ng luciferase per mg tissue
      protein, but relatively low expression in SK-BR-3 cells in vitro. Additionally,
      some of the complexes containing pre-condensed DNA look like 'map-pin' structures
      showing heads of the size of liposomes and short, stiff and tapering tails. The
      in vivo transfection activity of these preparations is highest. Similar complexes
      containing DOPE rather than Chol as helper lipid precipitate in the presence of
      serum and especially of cell medium and convert into hexagonal lipid (HII) phase.
      Such complexes, despite their high transfection activity in vitro, show very
      little transfection activity in vivo. These comparisons may help us to understand
      the fundamental difference between in vitro and in vivo activity of CLDC: high in
      vitro transfection activity seems to be associated with hexagonal lipid
      precipitates whereas high in vivo activity seems to be related with small,
      stabilized complexes, which in our case also exhibit some protrusions (map-pin
      structures).

PMID- 9767091
TI  - Herpesvirus thymidine kinase transgenes that do not cause male sterility are
      aberrantly transcribed and translated in the testis.
AB  - Mice that carry the wild-type herpes simplex virus type 1 (HSV1) thymidine kinase
      (tk) gene coupled to the bovine thyroglobulin (bTG) promoter (bTG-tk1 mice)
      express viral TK at a high level in the thyroid gland, and at an equally high
      level, ectopically, in the testis, which renders the males sterile. When the bTG
      promoter was coupled either to a variant of HSV1-tk (differing from the wild type
      in 2 nucleotides) (bTG-tk1alpha mice) or to the herpes simplex virus type 2
      (HSV2) tk gene (bTG-tk2 mice) viral TK was expressed at high levels in the
      thyroid gland, and much lower levels in the testis, which causes a reduction in
      male fecundity rather than sterility. Here, we compare the expression of the
      three transgenes in the two tissues. Thyroids of all mice exhibited a 1.3 kb RNA
      initiated at or near the bTG cap site. Testes of all mice exhibited mainly 5'-end
      shortened RNAs (bTG-tk1 and bTG-tk1alpha mice, approx. 1.2 kb and 0.9 kb; bTG-tk2
      mice, approx. 1.2 kb) initiated from cryptic initiation sites in the HSV1-tk and
      HSV2-tk coding regions. Also, less abundant RNAs initiated near the bTG cap site
      were expressed from all three transgenes. Thyroids of bTG-tk1 and bTG-tk1alpha
      mice contained the full-length HSV-TK protein and a truncated variant previously
      shown to originate at a non-ATG start codon. Testes of these mice exhibited both
      proteins but relatively less of the full-length protein. We attribute the high
      level of viral TK in the testes of bTG-tk1 mice to the expression of a
      predominant protein of Mr 39000 that originates from ATG-2. Thyroid and testis of
      bTG-tk2 mice contained only the full-length HSV2-TK protein.

PMID- 9767092
TI  - Cloning and expression of the Zymomonas mobilis pyruvate kinase gene in
      Escherichia coli.
AB  - The homotetrameric pyruvate kinases (PK) constitute a fine example of allosteric
      enzymes subjected to sophisticated regulatory mechanisms. We have cloned and
      sequenced the Zymomonas mobilis structural gene for the first prokaryotic dimeric
      PK, as an initial step toward understanding the peculiar properties of this
      enzyme. The deduced amino acid sequence of the pyk gene consists of 475 residues
      with a calculated molecular mass of 51.4kDa and exhibits up to 50% sequence
      identity with other PKs. Heterologous expression in Escherichia coli was not
      obtained from the native promoter, but only when the pyk gene was under the
      control of a strong inducible promoter when a ribosome-binding site was present
      upstream of the putative TTG start codon of the pyk gene. Kinetic
      characterization of PK in concentrated crude cell extracts showed that the enzyme
      is not activated by sugar phosphates or AMP but is slightly inhibited by ATP.
      Thus, PK of Z. mobilis is unique among the characterized prokaryotic PKs due to
      its high activity in the absence of any allosteric activator. Amino acid sequence
      alignments revealed that glutamate 381 may play a role in ineffective binding of
      the usual PK activator, fructose-1,6-bisphosphate.

PMID- 9767093
TI  - Stimulation of monocytes and platelets by short-chain phosphatidylcholines with
      and without terminal carboxyl group.
AB  - Oxidation of unsaturated phosphatidylcholine (PC) produces fragmented
      phospholipids which have similar bioactivities as the platelet-activating factor
      (PAF, 1-O-alkyl-2-acetyl-PC). Since a large number of molecular species are
      produced upon PC oxidation, the active ingredients have not been identified. We
      synthesized several short-chain PCs which are known to be characteristic PC
      oxidation products to test their PAF-like activity. The synthetic PCs contained
      palmitoyl or hexadecyl residues (both C16) in sn-1 position, and propionyl (C3),
      valeroyl (C5), succinyl (C4 with omega-carboxyl), glutaroyl (C5 with omega
      carboxyl), or suberoyl (C8 with omega-carboxyl) residues in sn-2 position.
      Biological activity was measured by: (1) increase of intracellular calcium in
      human monocytes; (2) [3H]serotonin release from rabbit platelets; and (3)
      aggregation of human platelets. Specificity of the cellular response was tested
      by inhibition with the PAF-receptor antagonists BN 52021 and WEB 2086. Synthetic
      PC oxidation products activated both monocytes and platelets in a PAF-specific
      manner. The effective concentration varied with respect to assay system and
      chemical structure. In general, 1-hexadecyl-PCs were more effective than 1
      palmitoyl-PCs, while increasing chain length in sn-2 position lowered biological
      activity. However, several 1-palmitoyl-PCs activated monocytes in concentrations
      between 10-8 and 10-6 M. In contrast, platelets were less susceptible to 1
      palmitoyl-PCs. No significant difference was found between 2-valeroyl-PC (C5 with
      omega-methyl) and 2-glutaroyl-PC (C5 with omega-carboxyl). The data suggest that
      typical products of PC oxidation, containing propionyl, succinyl, or glutaroyl
      residues in sn-2 position, display PAF-like activity at micromolar
      concentrations.

PMID- 9767094
TI  - Dynamic developmental expression of smallminded, a Drosophila gene required for
      cell division.
AB  - Here we describe the expression pattern of the smallminded (smid) gene during
      Drosophila development and investigate the phenotype of a null mutant. In situ
      hybridisation reveals the ubiquitous expression of smid transcript throughout
      early embryonic stages until the extended germ band stage, after which expression
      becomes localised to the neurogenic ectoderm and gonad. Post-embryonic expression
      is restricted to tissues engaged in the developmental programme of the adult fly:
      the re-enlarged neuroblasts; imaginal disks; histoblast nests; and precursors of
      adult muscles. The correlation of smid expression with mitotic activity suggests
      a cell cycle function which is confirmed by the observed phenotype of a smid null
      mutant characterised by an abnormally small CNS, due to defective mitosis of post
      embryonic neuroblasts and their subsequent death by apoptosis.

PMID- 9767095
TI  - Measurement of the extracellular H2O2 in the brain by microdialysis.
AB  - This paper reports on the protocol for the determination of H2O2 in the brain
      using in vivo microdialysis coupled with fluorometry of dichlorofluorescin
      oxidation. We applied this protocol to monitor changes in the concentration of
      H2O2 in the brain, in vivo, during ischemia and reperfusion. Using this method,
      changes in the level of H2O2 in the brain during ischemia and reperfusion were
      effectively determined. The present protocol provides a novel tool to study the
      production of reactive oxygen species in the brain.

PMID- 9767096
TI  - Fructans interact strongly with model membranes.
AB  - Bacterial fructans with a high degree of polymerisation cause a very large
      increase in surface pressure of lipid monolayers at the air-water interface with
      a broad range of lipids, including phosphatidylethanolamine and several types of
      phosphatidylcholines. The surface active effect of fructans contrasts strongly
      with the maximal effects observed for trehalose, sucrose and glucose under
      comparable conditions (20 and 0.6 mN/m for fructans and the other sugars,
      respectively). The results demonstrate a profound and specific membrane
      interaction of the fructans which is probably very different from the effect of
      the smaller carbohydrates. The fructan concentrations used in this study are
      within the physiological range observed in fructan-accumulating plants. The
      suggested water-stress protective effect of fructans may be induced by membrane
      fructan interaction which prevent lipid condensation and phase transitions to
      take place.

PMID- 9767097
TI  - An in vitro technique for tracing neuronal connections in the teleost brain.
AB  - The availability of neuronal tract-tracing techniques has been fundamental to the
      development of the neurosciences. While most of the previously described methods
      are performed in vivo, in the present paper, detailed protocols are reported for
      tracing neuronal connections in an in vitro preparation. This technique, tested
      in various neural systems of the teleost brain, allows precise application of
      tracer substance(s) under visual control. After the isolation of the brain, the
      tissue is kept alive by superfusion with oxygenated artificial cerebrospinal
      fluid in a slice chamber. Neuronal connections are traced by the application of
      crystals of biocytin or dextran-tetramethylrhodamine to the region of interest.
      Following intracellular transport over 8-18 h, the tissue is fixed and processed
      histochemically for visualization of structures filled with the tracer substance.
      This method can readily be modified for double labelling. Step-by-step procedures
      are outlined for (a) the simultaneous detection of two tracer substances in the
      same tissue sample, (b) the combination of tract tracing with the
      immunohistochemical identification of various biochemical markers such as
      'classical' transmitters and neuropeptides, and (c) the visualization of both
      traced structures and mitotically active cells labelled with the thymidine
      analogue 5-bromo-2'-deoxyuridine. By exhibiting a high degree of efficiency, the
      described in vitro tract-tracing technique represents also a significant
      contribution towards a reduction of living animals in neurobiological
      experimentation.

PMID- 9767098
TI  - Role of adenine nucleotides, molecular chaperones and chaperonins in
      stabilization of DnaA initiator protein of Escherichia coli.
AB  - DnaA protein of Escherichia coli is a sequence-specific DNA binding protein
      required for the initiation of DNA replication from the chromosomal origin, oriC,
      and of several E. coli plasmids. At a moderate ionic strength, purified DnaA
      protein has a strong tendency to aggregate; the self-aggregate form is inactive
      in DNA replication. Binding of ATP or ADP to DnaA protein protected it from
      aggregation to maintain its replication activity. AMP or cyclic AMP had no
      protective effect. The molecular chaperone DnaK protected DnaA protein from
      aggregation with or without ATP. DnaJ and GrpE were not stimulatory. Chaperonins
      GroEL and GroES were also able to prevent aggregation but only in the presence of
      ATP. The studies presented here show that for DnaA protein to be active in the
      initiation of DNA replication, it must be prevented from forming a self-aggregate
      by the binding of adenine nucleotides, and/or by the action of molecular
      chaperones.

PMID- 9767099
TI  - A novel spliced transcript of human CLAPS2 encoding a protein alternative to
      clathrin adaptor protein AP17.
AB  - Transcripts of genes encoding proteins of clathrin complexes have been reported
      to undergo tissue-specific alternative splicing. AP17, encoded by human CLAPS2
      cDNA, is the small chain of the major clathrin adaptor complex AP-2 associated
      with mammalian plasma membranes. In this study, two cDNAs were isolated from a
      cDNA library of human blood cells. Whereas one cDNA encoded AP17, the other cDNA
      encoded a putative novel protein variant, termed AP17Delta. Both coding regions
      were completely sequenced. Consisting of 142aa residues, the predicted protein
      AP17Delta of 12kDa lacks 38aa residues of AP17. Using specific primers for RT
      PCR, mRNAs for AP17Delta and AP17 were found in leukocytes and cultured leukemia
      cells. The finding of a putative intron in a human EST cDNA clone suggests that
      mRNAs for AP17 and AP17Delta are formed by alternative splicing. In addition, the
      identity of human and rat AP17 amino acid sequences is demonstrated.

PMID- 9767100
TI  - On the role of sterol in the formation of the amphotericin B channel.
AB  - Amphotericin B is an antimycotic agent that has been studied for a long time,
      both because of its pharmacological action and the interest in understanding how
      this ionic channel works. It has been proposed that the channel is formed by a
      barrel of monomers, and that the presence of sterol is needed for the formation
      of such a barrel. As a matter of fact this need of a sterol has been used as a
      guiding idea in attempts to design derivatives more efficient in the
      discrimination of the cholesterol containing membranes, as compared to the
      ergosterol containing ones, henceforth diminishing the unwanted side effects in
      its pharmacological use. In this work we show that unitary channels that appear
      in a cholesterol containing membrane also appear when this membrane is free of
      cholesterol. We prove this to be the case for two membranes, a biological one,
      asolectin, and a synthetic one, DMPC. We then advance the idea that the role of
      sterols in the formation of the amphotericin B channel is related to the effects
      they have on the structure of the membrane itself, rather than to a direct
      involvement in the channel formation. We further look into the effect that
      different cholesterol concentrations in the membrane produce on the single
      channel properties.

PMID- 9767101
TI  - Natural forms of shed tumor gangliosides.
AB  - Gangliosides shed by tumor cells are immunosuppressive molecules, but the
      mechanisms of shedding are poorly understood. We therefore conducted a
      comprehensive study of shedding to identify the natural forms of shed
      gangliosides. By chemical detection and mass spectrometric analysis of the
      gangliosides of YAC-1 murine lymphoma cells, we first confirmed that all major
      ganglioside species are released. Then, by the combination of metabolic and cell
      surface radiolabeling, we further demonstrated that gangliosides are released
      directly from the cell plasma membrane, i.e. by shedding. Ultracentrifugation
      separated the conditioned medium of metabolically radiolabeled cells cultured in
      either serum-free or serum-containing medium into: (1) a pellet of 100-200 nm
      membrane vesicles (visualized by electron microscopy) containing nearly one-third
      of total shed gangliosides; and (2) the supernatant, which contained soluble
      gangliosides (two-thirds of the total shed gangliosides). Although the
      ganglioside concentration in the conditioned medium (6-14x10-8 M) was above the
      critical micelle concentration of purified YAC-1 gangliosides (<1x10-8 M), by gel
      filtration >90% of the soluble gangliosides were found in monomeric form (MW <2
      kDa) and only <10% in micelles (130 kDa). Ultrafiltration of fresh conditioned
      medium likewise showed the existence of monomers, and the findings were confirmed
      in human Daoy medulloblastoma and mouse MEB4 melanoma cells. Thus, in their
      natural states, shed tumor cell gangliosides exist in three forms: membrane
      vesicles, micelles, and monomers.

PMID- 9767102
TI  - The Drosophila putative kinase linotte (derailed) prevents central brain axons
      from converging on a newly described interhemispheric ring.
AB  - The lio gene encodes a putative receptor tyrosine kinase, with unique motifs both
      in the extracellular and catalytic domains (Dura, J.-M., Preat, T., Tully, T.,
      1993. Identification of linotte, a new gene affecting learning and memory in
      Drosophila melanogaster. J. Neurogenet. 9, 1-14). We show here that a complete
      deletion of lio activity causes specific structural defects in the adult brain.
      Gal4 enhancer-trap lines used as cell markers revealed that in lio mutants
      central brain axons behave as if they were abnormally attracted by the midbrain
      area. The Lio protein is expressed in third instar larvae in a few cells at the
      junction of the cerebral hemispheres. These glial cells form a newly described
      ring structure, showing an invariable fibrous organization. In the wild-type this
      ring disappears at midpupation. Our results indicate that the Lio putative kinase
      plays a major role in the modeling of the adult brain by controlling the fate of
      the transient interhemispheric ring.

PMID- 9767103
TI  - Molecular analysis of the split cox1 gene from the Basidiomycota Agrocybe
      aegerita: relationship of its introns with homologous Ascomycota introns and
      divergence levels from common ancestral copies.
AB  - The Basidiomycota Agrocybe aegerita (Aa) mitochondrial cox1 gene (6790
      nucleotides), encoding a protein of 527aa (58377Da), is split by four large
      subgroup IB introns possessing site-specific endonucleases assumed to be involved
      in intron mobility. When compared to other fungal COX1 proteins, the Aa protein
      is closely related to the COX1 one of the Basidiomycota Schizophyllum commune
      (Sc). This clade reveals a relationship with the studied Ascomycota ones, with
      the exception of Schizosaccharomyces pombe (Sp) which ranges in an out-group
      position compared with both higher fungi divisions. When comparison is extended
      to other kingdoms, fungal COX1 sequences are found to be more related to algae
      and plant ones (more than 57.5% aa similarity) than to animal sequences (53.6% aa
      similarity), contrasting with the previously established close relationship
      between fungi and animals, based on comparisons of nuclear genes. The four Aa
      cox1 introns are homologous to Ascomycota or algae cox1 introns sharing the same
      location within the exonic sequences. The percentages of identity of the intronic
      nucleotide sequences suggest a possible acquisition by lateral transfers of
      ancestral copies or of their derived sequences. These identities extend over the
      whole intronic sequences, arguing in favor of a transfer of the complete intron
      rather than a transfer limited to the encoded ORF. The intron i4 shares 74% of
      identity, at the nucleotidic level, with the Podospora anserina (Pa) intron i14,
      and up to 90.5% of aa similarity between the encoded proteins, i.e. the highest
      values reported to date between introns of two phylogenetically distant species.
      This low divergence argues for a recent lateral transfer between the two species.
      On the contrary, the low sequence identities (below 36%) observed between Aa i1
      and the homologous Sp i1 or Prototheca wickeramii (Pw) i1 suggest a long
      evolution time after the separation of these sequences. The introns i2 and i3
      possessed intermediate percentages of identity with their homologous Ascomycota
      introns. This is the first report of the complete nucleotide sequence and
      molecular organization of a mitochondrial cox1 gene of any member of the
      Basidiomycota division.

PMID- 9767104
TI  - cDNA cloning and Escherichia coli expression of UK114 tumor antigen.
AB  - Experimental evidence indicates that the antineoplastic effects of UK101, a goat
      liver perchloric acid extract, is likely due to one of its constituent proteins:
      the 14 kDa protein named UK114. The cDNA encoding UK114, obtained by PCR
      methodologies, contains an open reading frame coding for a protein of 137 amino
      acids with a theoretical molecular mass of 14298 Da. It shows high sequence
      homology with a 14 kDa protein identified in human, rat and Mus musculus tissues
      which is likely involved in the inhibition of cell-free protein synthesis.
      Northern blot analysis indicated that the transcript is present in variable
      amounts in a wide range of human tissues. Genomic Southern blots revealed that
      the UK114 mRNA in goat as well as in human is encoded by a single gene, as is the
      case in rat. The expression system for UK114 was constructed under the control of
      the PL promoter from bacteriophage lambda and the cDNA coding region has been
      highly expressed in Escherichia coli as a thioredoxin fusion protein. The
      recombinant UK114, purified to homogeneity, is immunoreactive to rabbit antisera
      prepared against UK101 or native UK114, as well as to sera of UK101-treated
      cancer patients. It inhibits cell-free protein synthesis at 8 microM
      concentration.

PMID- 9767105
TI  - Ionic channels formed by a primary amphipathic peptide containing a signal
      peptide and a nuclear localization sequence.
AB  - The peptide SP-NLS (Ac-Met-Gly-Leu-Gly-Leu-His-Leu-Leu-Leu-Ala10-Ala-Ala-Leu-Gln
      Gly- Ala -Lys-Lys-Lys-Arg20-Lys-Val-NH-CH2-CH2-SH) is composed of a hydrophobic
      signal sequence (SP, Met-1 to Ala-16) followed by a polycationic nuclear
      localization sequence (NLS, Lys-17 to Val-22) terminated by a cysteamide group.
      Designed to act as drug carrier this primary amphipathic peptide proved cytotoxic
      and bactericidal when used at high concentrations, probably by inducing the
      formation of ion channels. In this work, we show that indeed SP-NLS exhibits a
      pore-forming activity when incorporated into planar lipid bilayers and Xenopus
      laevis oocyte plasma membranes, with conductance values of 25 pS in 0.1 M NaCl.
      In both membranes, the insertion of the peptide was voltage-triggered whereas the
      induced conductances proved almost voltage-independent. Moreover, SP-NLS ion
      channels were selective for monovalent cations
      (K+>Na+>Li+>tetraethylammonium+>choline+). The ion channel activity of this type
      of peptides thus provides some insight on their toxicity but also on the
      mechanism involved for their membrane crossing process.

PMID- 9767106
TI  - TUNEL, Hoechst and immunohistochemistry triple-labelling: an improved method for
      detection of apoptosis in tissue sections--an update.
AB  - We describe an updated protocol which allows the combination of the previously
      described TUNEL and Hoechst 33342 double-labelling (G. Whiteside, N. Cougnon,
      S.P. Hunt, R. Munglani, An improved method for the detection of apoptosis in
      tissue sections and cell culture, using the TUNEL technique combined with Hoechst
      stain, Brain Res. Protocols, 2, 1998, 160-164 [3]), with immunohistochemistry.
      The inclusion of the immunohistochemistry step allows identification of apoptosis
      in distinct cell types by using cell specific markers. It also permits
      investigation into the proteins expressed in cells undergoing apoptotic cell
      death. We have evaluated the triple staining in sections of post-axotomy neonatal
      dorsal root ganglia.

PMID- 9767107
TI  - lacZ transgenic mice to monitor gene expression in embryo and adult.
AB  - In transgenic experiments, lacZ can be used as a reporter gene for activity of a
      given promoter. Its main advantage is the ease of visualization in situ, on
      sections or in whole mount preparations, and the availability of simple
      protocols. In the following, we describe our procedure for detecting promoter
      activity in transgenic mice, including choice of lacZ vectors, generation of the
      transgenic mice, and analysis of expression. We had recently used this protocol
      to detect tyrosinase gene promoter activity in embryonic and adult brain.

PMID- 9767108
TI  - Comparison of sequences of a transcriptional coactivator MBF2 from three
      Lepidopteran species Bombyx mori, Bombyx mandarina and Samia cynthia.
AB  - MBF2 was first isolated from the silkworm Bombyx mori as a positive cofactor that
      activates transcription through its interaction with TFIIA. To identify conserved
      domain(s) within the MBF2 molecule, we isolated cDNAs encoding MBF2 homologues
      from other silkworms Bombyx mandarina and Samia cynthia. Bacterially expressed
      and purified MBF2 of B. mandarina and S. cynthia activated transcription in
      vitro. The predicted amino acid sequences of MBF2 from two Bombyx species share
      97% homology. When we compared between B. mori and S. cynthia factors, the
      homology reduced to 50%. Four regions in MBF2 are conserved among these three
      species. Two of them are present in the middle region of MBF2 that is essential
      for the transcriptional activation.

PMID- 9767110
TI  - Expression and characterization of human group V phospholipase A2.
AB  - Group V phospholipase A2 (GV-PLA2) has been shown to be involved in signal
      transduction and inflammatory processes in cellular studies, but the physical and
      biochemical properties of this important enzyme have been unclear. We report the
      over-expression and characterization of GV-PLA2. The GV-PLA2 cDNA was synthesized
      from human heart polyA+ mRNA by RT-PCR, and an expression construct containing
      the GV-PLA2 was established. After expression in Escherichia coli cells, the
      protein was solubilized and purified to homogeneity in a single step using nickel
      affinity chromatography. The purified GV-PLA2 protein was folded to form active
      enzyme. The recombinant GV-PLA2 has an absolute requirement for Ca2+ for
      enzymatic activity. The optimum pH for this enzyme is pH 8.5 in Tris-HCl buffer
      with sonicated vesicles as substrate. GV-PLA2 preferentially hydrolyzes
      phosphatidylethanolamine (PE) vesicles compared to phosphatidylcholine (PC)
      vesicles. However, hydrolysis of PC and PE is equivalent in mixed vesicles of the
      phospholipids. The fatty acid preference of GV-PLA2 is
      linoleoyl>palmitoyl>arachidonyl with a PC head group and sonicated vesicles. 3-(3
      Actamide-1-benzyl-2-ethylindolyl-5-oxy)propane phosphonic acid (LY311727), a
      potent inhibitor of human group IIA PLA2, strongly inhibits GV-PLA2 with an IC50
      value of about 36 nM which is comparable to its inhibition of group IIA PLA2.

PMID- 9767109
TI  - High mobility group 1 (HMG1) protein in mouse preimplantation embryos.
AB  - High mobility group 1 protein (HMG1) has traditionally been considered a
      structural component of chromatin, possibly similar in function to histone H1. In
      fact, at the onset of Xenopus and Drosophila development, HMG1 appears to
      substitute for histone H1: HMG1 is abundant when histone H1 is absent after the
      midblastula transition histone H1 largely replaces HMG1. We show that in early
      mouse embryos the expression patterns of HMG1 and histone H1 are not
      complementary. Instead, HMG1 content increases after zygotic genome activation at
      the same time as histone H1. HMG1 does not remain associated to mitotic
      chromosomes either in embryos or somatic cells. These results argue against a
      shared structural role for HMG1 and histone H1 in mammalian chromatin.

PMID- 9767111
TI  - Insulin inhibits surfactant protein A and B gene expression in the H441 cell
      line.
AB  - Fetuses of mothers with uncontrolled gestational diabetes have an increased risk
      of developing neonatal respiratory distress syndrome and are frequently
      hyperinsulinemic, thus it has been proposed that high levels of insulin delay
      fetal lung maturation. We have shown previously that insulin inhibits the
      accumulation of mRNA for the surfactant-associated proteins A and B (SP-A and SP
      B) in human fetal lung explants maintained in vitro. To test the hypothesis that
      the inhibitory effects of insulin on the surfactant proteins are the result of a
      direct action of insulin on the lung epithelial cell, we evaluated the effects of
      insulin in the H441 cell line, a human pulmonary adenocarcinoma cell line that
      expresses SP-A and SP-B mRNA. We observed that insulin treatment for 48 h
      decreased SP-A mRNA and protein levels in a concentration-dependent manner when
      compared to controls. The inhibitory effect of insulin on SP-A mRNA levels was
      apparent as early as after 4 h of exposure. SP-B mRNA levels were also
      significantly decreased by insulin in a concentration-dependent manner. Insulin,
      at 2.5 microg/ml, inhibited SP-A gene transcription by approx. 67%, and inhibited
      SP-B gene transcription by about 32%. There was no significant effect of insulin
      on SP-A or SP-B mRNA stability. Thus, we have observed a pattern of insulin
      inhibition of SP-A and SP-B gene expression in the H441 lung epithelial cell line
      similar to that previously observed in human fetal lung explants, which are
      comprised of both epithelial and mesenchymal cells. Our findings provide further
      evidence that insulin may delay fetal lung maturation by inhibiting SP-A and SP-B
      gene expression. Furthermore, our findings suggest that the inhibitory effects of
      insulin are, at least partially, the result of a direct action on the lung
      epithelial cell.

PMID- 9767112
TI  - Characterization of ATP and P2 agonists binding to the cardiac plasma membrane
      P1,P4-diadenosine 5'-tetraphosphate receptor.
AB  - P1,P4-Diadenosine 5'-tetraphosphate (Ap4A) acts as an extracellular modulator
      through its interaction with purinoceptors. Our laboratory has demonstrated the
      presence of an Ap4A receptor in cardiac tissue [1,2]. Due to the rapid hydrolysis
      of ATP by cardiac membranes the relationship of ATP and Ap4A binding to
      purinoceptors on cardiac membranes has not been characterized. In this
      communication we used two approaches to determine the relationship of ATP to the
      Ap4A receptor. Radioligand binding carried out with [alpha-32P]Ap4A and adenosine
      5'-O-?3-thiotriphosphate? ([gamma-35S]ATPgammaS) demonstrates the presence of a
      single high affinity binding site for Ap4A and the presence of two binding sites
      for ATPgammaS. The second approach utilized immunoaffinity purified Ap4A receptor
      that was shown to be free of ATPase and Ap4Aase activities. Non-radiolabeled Ap4A
      and ATPgammaS effectively inhibited photocrosslinking of [alpha-32P]8-N3Ap4A to
      the receptor polypeptide while ATP was a much less effective inhibitor.
      Furthermore, on plasma membranes [alpha-32P]8-N3Ap4A photocrosslinked to only a
      50 kDa polypeptide. These data are consistent with Ap4A interacting with a
      homogeneous population of receptors on cardiac plasma membranes but with ATP
      having a low affinity for the receptor.

PMID- 9767113
TI  - Genomic organization of four beta-1,4-endoglucanase genes in plant-parasitic cyst
      nematodes and its evolutionary implications.
AB  - The genomic organization of genes encoding beta-1,4-endoglucanases (cellulases)
      from the plant-parasitic cyst nematodes Heterodera glycines and Globodera
      rostochiensis (HG-eng1, Hg-eng2, GR-eng1, and GR-eng2) was investigated. HG-eng1
      and GR-eng1 both contained eight introns and structural domains of 2151 and
      2492bp, respectively. HG-eng2 and GR-eng2 both contained seven introns and
      structural domains of 2324 and 2388bp, respectively. No significant similarity in
      intron sequence or size was observed between HG-eng1 and HG-eng2, whereas the
      opposite was true between GR-eng1 and GR-eng2. Intron positions among all four
      cyst nematode cellulase genes were conserved identically in relation to the
      predicted amino acid sequence. HG-eng1, GR-eng1, and GR-eng2 had several introns
      demarcated by 5'-GCellipsisAG-3' in the splice sites, and all four nematode
      cellulase genes had the polyadenylation and cleavage signal sequence 5'-GAUAAA-3'
      both rare occurences in eukaryotic genes. The 5'- flanking regions of each
      nematode cellulase gene, however, had signature sequences typical of eukaryotic
      promoter regions, including a TATA box, bHLH-type binding sites, and putative
      silencer, repressor, and enhancer elements. Database searches and subsequent
      phylogenetic comparison of the catalytic domain of the nematode cellulases placed
      the nematode genes in one group, with Family 5, subfamily 2, glycosyl hydrolases
      from Scotobacteria and Bacilliaceae as the most homologous groups. The overall
      amino acid sequence identity among the four nematode cellulases was from 71 to
      83%, and the amino acid sequence identity to bacterial Family 5 cellulases ranged
      from 33 to 44%. The eukaryotic organization of the four cyst nematode cellulases
      suggests that they share a common ancestor, and their strong homology to
      prokaryotic glycosyl hydrolases may be indicative of an ancient horizontal gene
      transfer.

PMID- 9767114
TI  - Experimental protocol for studying delayed effects of in vitro ischemia on
      neurotransmitter release from brain slices.
AB  - The mechanisms by which ischemic injury leads to delayed neuronal death are not
      completely understood. Notably, no data are so far available on the modifications
      in neurosecretory responses evoked by a period of ischemia. Superfused brain
      slices represent a useful preparation in studying the effects of in vitro
      ischemia on neurotransmitter release. Using this experimental model we describe a
      protocol which allows to study not only the immediate effects of an ischemic
      insult, but also, more interestingly, its delayed (1 h) effects on the release of
      different neurotransmitters. A first pulse (S1) of 50 mM KCl was applied at the
      60th min of perfusion and a second one was applied at the 210th min (S2). In
      vitro ischemia was performed from the 120th to the 150th min, during the
      inclusive period between the two depolarizing stimuli. The delayed effects of the
      ischemic treatment on slice response to KCl were calculated as S2/S1 ratio. This
      protocol allows to study neurotransmitter release mechanisms associated with
      postischemic neuronal death. Moreover it will be useful in the evaluation of the
      neuroprotective potential of new drugs.

PMID- 9767115
TI  - Effect of dietary (n-9), (n-6) and (n-3) fatty acids on membrane lipid
      composition and morphology of rat erythrocytes.
AB  - Studies focused on the intake of different dietary fats have shown changes in
      membrane lipid composition and, as a result, alterations in membrane physical
      properties. These changes affect erythrocyte morphology, receptor activity and
      oxygen transport, among others. Here, we compare the effects of diets exclusively
      differing in the type of fat (olive oil rich in monounsaturates, sunflower oil
      rich in n-6 polyunsaturates and fish oil rich in n-3 polyunsaturates) on fatty
      acid composition of plasma and erythrocyte membranes and erythrocyte morphology
      under scanning electron microscopy in rats. Monounsaturates are highest in
      animals fed olive oil diets; as are linoleic and arachidonic acids in sunflower
      oil-fed animals and n-3 PUFAs in fish oil-fed animals. The lowest levels of
      arachidonic acid are found in fish oil-fed animals and so are n-3 PUFAs in
      sunflower oil-fed animals. Our results show that sunflower oil-fed animals
      present lower discocyte, the major cell shape related to tissue oxygen supply,
      and higher codocyte percentages than olive oil- and fish oil-fed groups.
      Echinocyte percentage is higher in fish oil-fed animals with respect to the other
      two groups. The collective data indicate that olive oil elevates monounsaturates
      and the number of discocytes, pointing out a possible beneficial aspect of this
      dietary fat.

PMID- 9767116
TI  - Positive and negative control of Serrate expression during early development of
      the Drosophila wing.
AB  - The product of the Drosophila gene Serrate acts as a short-range signal during
      wing development to induce the organising centre at the dorsal/ventral
      compartment boundary, from which growth and patterning of the wing is controlled.
      Regulatory elements reflecting the early Serrate expression in the dorsal
      compartment of the wing disc have recently been confined to a genomic fragment in
      the 5'-upstream region of the gene. Here we present data to suggest that this
      fragment responds to various positive and negative inputs required for the early
      Serrate expression. First, activation and maintenance of expression in the dorsal
      compartment of the wing discs of second and early third instar larvae depends on
      apterous, as revealed by reporter gene expression in discs either lacking or
      ectopically expressing apterous. Second, transcriptional downregulation during
      third larval instar is mediated by hiiragi. Finally, this regulatory element
      responds to Delta signalling in a nonautonomous way to maintain Serrate
      expression along the dorsal margin. The results clearly show that some of the
      previously described transactivators of Serrate protein expression, e.g. fringe,
      act on elements required for later aspects of Serrate expression.

PMID- 9767117
TI  - Parallel regional quantification of choline acetyltransferase and cholinesterase
      activity in the central nervous system of an invertebrate (Sepia officinalis).
AB  - The present study describes (i) a procedure to dissect the central nervous system
      of the cuttlefish (Cephalopod) into ten, functionally distinct, anatomical
      regions of interest and (ii) the parallel measurement of acetylcholine synthesis
      (choline acetyltransferase) and degradation (cholinesterase) activities. Both
      aspects (dissection and parallel quantification of acetylcholine synthesis and
      degradation) could be of great importance for quantitative regional studies in
      neurochemistry in this animal model, it is interesting to study the cellular and
      molecular mechanisms involved in learning and aging processes. The parallel
      quantification of acetylcholine synthesis and degradation applicable to any
      animal model is pivotal since both enzymes are essential for the cholinergic
      neurotransmission and may be differentially modulated by specific functions such
      as learning and aging processes. Furthermore, since choline acetyltransferase and
      cholinesterase show different localization into the brain, their parallel
      quantification may underlie the involvement of cholinesterase in non-cholinergic
      functions, which remain unclear throughout the animal kingdom.

PMID- 9767118
TI  - cDNA cloning of two splice variants of a human copper-containing monoamine
      oxidase pseudogene containing a dimeric Alu repeat sequence.
AB  - Two alternatively spliced transcripts, psiHLAO1 and psiHLAO2, of a copper
      containing monoamine oxidase pseudogene have been isolated from a human-liver
      cDNA library. The larger psiHLAO1 cDNA (2073bp) contains a 5'-flanking segment of
      134bp, followed by an apparent open reading frame (ORF) of 1725bp. The deduced
      amino acid sequence of this ORF (574 residues) shares 81.0% similarity with the
      763-residue monoamine oxidase from human placenta (HPAO) (the N-terminal 533
      residues of psiHLAO1 share 86.7% similarity with HPAO). The psiHLAO1 ORF is
      interrupted by an in-frame stop codon corresponding to amino acid 225 and
      terminates within a type S(a) dimeric Alu repeat sequence. psiHLAO2 appears to be
      an alternatively spliced variant of psiHLAO1 that has 413 bases of psiHLAO1
      excised according to the 'GT-AG' rule. The slightly longer 3' end of the psiHLAO2
      transcript shows that the Alu repeat is followed by an 11-bp poly(A) tract that,
      in turn, is followed by an AT-rich (81%) sequence of 105bp. A reverse
      transcriptase-polymerase chain reaction (RT-PCR) protocol was used to confirm
      that both psiHLAO1 and psiHLAO2 are transcribed in human liver and placenta. A
      search of the expressed sequence tag (EST) database indicates that, like HPAO,
      psiHLAO derives also from the region 17q21 of the human genome.

PMID- 9767119
TI  - Chemical cross-linking of ethidium to DNA by glyoxal.
AB  - Ethidium was found to be efficiently cross-linked to DNA by glyoxal. Kinetic
      studies showed that the rate of the cross-linking reaction is strongly dependent
      on the glyoxal concentration. Comparative studies using a series of
      phenanthridines and acridines showed that NH2 groups at both the 2 and 7
      positions on the phenanthridine ring are necessary for efficient cross-linking.
      Studies using synthetic polydeoxynucleotides showed that the 2-amino group of
      guanine is absolutely required for cross-linking. Fluorescence contact energy
      transfer and relative viscosity experiments showed that the cross-linked drug
      remains intercalated into DNA. DNA gel electrophoresis and melting studies
      demonstrated that cross-linked ethidium does not dissociate the DNA double helix
      to single strands.

PMID- 9767120
TI  - Molecular organisation of amphotericin B at the air-water interface in the
      presence of sterols: a monolayer study.
AB  - Using the monolayer technique to study the surface behaviour of systems
      consisting of amphotericin B (AmB) and various sterols, the components were found
      to interact with each other. The interactions observed are accounted for by
      postulating that, at low surface pressures, AmB and different sterols form mixed
      films where the former lies parallel and the latter normal to the air-water
      interface in such a way that the polar groups in both components establish
      hydrogen bonds that lead to the formation of an AmB-sterol 'complex' of 2:1
      stoichiometry at the interface. At high surface pressures, AmB molecules
      rearrange themselves normal to the interface; this gives rise to the Van der
      Waals interactions between non-polar chains of both components that vary with the
      nature and composition of the system. The occurrence of these hydrophobic
      interactions prevents the desorption of AmB into the subphase, which is
      consistent with the positive excess areas of mixing obtained under these surface
      pressure conditions. Among the four sterols studied, ergosterol exhibits the
      strongest interaction with AmB and beta-sitosterol the weakest. Cholesterol and
      stigmasterol show intermediate behaviour.

PMID- 9767121
TI  - Effect of beta-cyclodextrin dietary supplementation on biliary proteins and their
      resulting cholesterol nucleating activity in pigs.
AB  - We explored the possibility that the biliary protein fraction may support part of
      the variation in the nucleating activity previously measured in gallbladder biles
      of pigs. Eighteen gallbladder aspirates freshly obtained from three dietary
      groups (0, 5, or 10% beta-cyclodextrin) of six pigs were chromatographed to
      purify their total protein fraction. Proteins were quantified, and analysed
      through electrophoresis and immunoblotting or enzyme-linked immunosorbent assay
      for albumin, and five putative effectors of cholesterol crystallisation, mucins,
      immunoglobulin A, 130 kDa, apolipoprotein A-I, and anionic polypeptide fraction.
      Each total protein fraction was also assayed for its ability to influence
      cholesterol precipitation, when added to supersaturated model bile. The current
      data provided evidence that the cholesterol crystallisation-promoting activity of
      biliary proteins in model biles increased with the beta-cyclodextrin dietary
      content. This occurred without any significant change in the total biliary
      protein content, but was associated with a significant decrease in the
      concentration of albumin and apolipoprotein A-I, resulting in changes in the
      overall balance of proteins in bile. Comparison of these results with the
      crystallisation figures previously obtained from the corresponding native biles
      led us to conclude that biliary proteins might influence the outcome of the
      crystallisation process, namely the final crystal concentration at equilibrium,
      but would not systematically represent a major driving force for determining the
      velocity of crystal formation in native bile of pigs.

PMID- 9767122
TI  - Cryopreservation of rat cortical synaptosomes and analysis of glucose and
      glutamate transporter activities, and mitochondrial function.
AB  - Direct comparisons of synaptic functional parameters in brain tissues from
      different groups of experimental animals and different samples from post mortem
      human brain are often hindered by the inability to perform assays at the same
      time. To circumvent these difficulties we developed methods for cryopreservation
      and long-term storage of neocortical synaptosomes. The synaptosomes are suspended
      in a cryopreservation medium containing 10% dimethylsulfoxide and 10% fetal
      bovine serum, and are slowly cooled to -80 degreesC and then stored in liquid
      nitrogen. The function of plasma membrane glucose and glutamate transporters, and
      mitochondrial electron transport activity and membrane potential were measured in
      fresh, cryopreserved (CP), and non-cryopreserved freeze-thawed (NC) synaptosomes.
      Glucose and glutamate transporter activities, and mitochondrial functional
      parameters in CP synaptosomes were essentially identical to those in fresh
      unfrozen synaptosomes. Glucose and glutamate transport were severely compromised
      in NC synaptosomes, whereas mitochondrial function and cellular esterase activity
      were largely maintained. Electron paramagnetic resonance studies in conjunction
      with a protein-specific spin label indicated that cryopreservation did not alter
      the physical state of synaptosomal membrane proteins. These methods provide the
      opportunity to generate stocks of functional synaptosomes from different
      experiments or post mortem samples collected over large time intervals.

PMID- 9767123
TI  - The mouse Fkh1/Mf1 gene: cDNA sequence, chromosomal localization and expression
      in adult tissues.
AB  - The 'winged helix' or 'forkhead' transcription factor gene family is defined by a
      common 100-amino-acid DNA-binding motif. Here, we describe the chromosomal
      position, start site of transcription, sequence and adult expression pattern of
      the mouse Fkh1/Mf1 (Forkhead homologue 1/mesoderm/mesenchyme forkhead 1) gene.
      This gene contains one exon and encodes a protein of 553 amino acids that is
      highly related to the mouse MFH1 protein. The Fkh1/Mf1 mRNA is expressed widely
      in adult tissues. Linkage analysis showed that the Fkh1/Mf1 gene is localized to
      chromosome 13 at 17.02cM from the centromer, in close proximity to Bmp6 and Hfh1,
      another distinct member of the winged helix gene family.

PMID- 9767124
TI  - Selective expression of specific histone H4 genes reflects distinctions in
      transcription factor interactions with divergent H4 promoter elements.
AB  - Expression of many histone H4 genes is stringently controlled during the cell
      cycle to maintain a functional coupling of histone biosynthesis with DNA
      replication. The histone H4 multigene family provides a paradigm for
      understanding cell cycle control of gene transcription. All functional histone H4
      gene copies are highly conserved in the mRNA coding region. However, the putative
      promoter regions of these H4 genes are divergent. We analyzed three
      representative mouse H4 genes to assess whether variation in H4 promoter
      sequences has functional consequences for the relative level and temporal control
      of expression of distinct H4 genes. Using S1 nuclease protection assays with gene
      specific probes and RNA from synchronized cells, we show that the mRNA level of
      each H4 gene is temporally coupled to DNA synthesis. However, there are
      differences in the relative mRNA levels of these three H4 gene copies in several
      cell types. Based on gel shift assays, nucleotide variations in the promoters of
      these H4 genes preclude or reduce binding of several histone gene transcription
      factors, including IRF2, HiNF-D, SP-1 and/or YY1. Therefore, differential
      regulation of H4 genes is directly attributable to evolutionary divergence in H4
      promoter organization which dictates the potential for regulatory interactions
      with cognate H4 transcription factors. This regulatory flexibility in H4 promoter
      organization may maximize options for transcriptional control of histone H4 gene
      expression in response to the onset of DNA synthesis and cell cycle progression
      in a broad spectrum of cell types and developmental stages.

PMID- 9767125
TI  - Water-absorbent polymer as a carrier for a discrete deposit of antisense
      oligodeoxynucleotides in the central nervous system.
AB  - One of the problems of introducing antisense oligodeoxynucleotides (ODN) into the
      central nervous system (CNS) is their rapid disappearance from the target site
      due to their dispersion and diffusion, which results in poor uptake and/or
      retention in cells (M. Morris, A.B. Lucion, Antisense oligonucleotides in the
      study of neuroendocrine systems, J. Neuroendocrinol. 7 (1995) 493-500; S. Ogawa,
      H.E. Brown, H.J. Okano, D.W. Pfaff, Cellular uptake of intracerebrally
      administrated oligodeoxynucleotides in mouse brain, Regul. Pept. 59 (1995) 143
      149) [2,5]. Recently, we adapted a new method using water-absorbent polymer (WAP;
      internally cross-linked starch-grafted-polyacrylates) as a carrier for antisense
      ODN. The polymer forms a hydro-gel after absorbing water which is chemically and
      biologically inert. In these studies, the polymer (powder-form) is fully swollen
      by physiological saline containing antisense ODN (0.2 micromol/ml) to make 80
      fold volume gel. Hydro-gel (1 microliter) is injected into the target site, and
      water solutes are assumed to be diffused stoichiometrically into CNS from the
      surface of the gel. Histological studies indicate that 24 h after the injection,
      antisense ODN (5'biotinylated-S-oligos of 15 mer) are distributed to within 800
      micrometer from the edge of the area where the gel is located and then gradually
      disappear from this area within days, but still remain within 300-micrometer
      distance 7 days later. Antisense ODN are effectively incorporated by all the cell
      types examined, i.e., neurons, astrocytes and microglias, and suppress the
      synthesis of the target protein. This method can be adapted to slow delivery of
      antisense ODN and other water soluble substances into the CNS.

PMID- 9767126
TI  - A chemotaxis cluster from Agrobacterium tumefaciens.
AB  - We report the DNA sequence of a 9.6-kb region of the Agrobacterium tumefaciens
      chromosome containing a putative 8-kb chemotaxis operon. The putative operon
      begins with orf1, whose predicted protein product shows strong sequence identity
      to methyl-accepting chemotaxis proteins (MCPs), followed by orf2, cheY1, cheA,
      cheR, cheB, cheY2, orf9, orf10. All of the identified homologues show a high
      degree of sequence conservation with their counterparts in the che operons from
      Sinorhizobium meliloti and Rhodobacter sphaeroides, and are arranged in a similar
      order. Mutations in orf1 and cheA result in impaired chemotaxis, whereas deletion
      of orf10, appears to have no effect on chemotaxis or motility. Although the
      putative operon does not contain a cheW homologue, heterologous probing and PCR
      using consensus primers indicates that cheW maps elsewhere in the Agrobacterium
      genome.

PMID- 9767127
TI  - Evidence of local conformational fluctuations and changes in bacteriorhodopsin,
      dependent on lipids, detergents and trimeric structure, as studied by 13C NMR.
AB  - We examined how the local conformation and dynamics of [3-13C]Ala-labeled
      bacteriorhodopsin (bR) are altered as viewed from 13C NMR spectra when the
      natural membrane lipids are partly or completely replaced with detergents. It
      turned out that the major conformational features of bR, the alphaII-helices, are
      generally unchanged in the delipidated or solubilized preparations. Upon partial
      delipidation or detergent solubilization, however, a significant conformational
      change occurs, ascribed to local conversion of alphaII-->alphaI-helix (one Ala
      residue involved), evident from the upfield displacement of the transmembrane
      helical peak from 16.4 ppm to 14.5 ppm, conformational change (one or two Ala
      residues) within alphaII-helices from 16.4 to 16.0 ppm, and acquired flexibility
      in the loop region (especially at the F-G loop) as manifested from suppressed
      peak-intensities in cross-polarization magic angle spinning (CP-MAS) NMR spectra.
      On the other hand, formation of monomers as solubilized by Triton X-100, Triton N
      101 and n-dodecylmaltoside is characterized by the presence of a peak at 15.5 ppm
      and a shifted absorption maximum (550 nm). The size of micelles under the first
      two conditions was small enough to yield 13C NMR signals observable by a solution
      NMR spectrometer, although 13C CP-MAS NMR signals were also visible from a
      fraction of large-sized micelles. We found that the 16.9 ppm peak (three Ala
      residues involved), visible by CP-MAS NMR, was displaced upfield when Schiff base
      was removed by solubilization with sodium dodecyl sulfate, consistent with our
      previous finding of bleaching to yield bacterioopsin.

PMID- 9767128
TI  - Cloning and identification of a phospholipase gene from vibrio mimicus.
AB  - The phospholipase gene phl was identified from Vibrio mimicus (ATCC33653) and
      sequenced. The entire open reading frame (ORF) was composed of 1410 nucleotides
      and encoding 470 amino acids. The phl was placed upstream of hemolysin gene
      (vmhA) with opposite direction of transcription. From the BLAST search program,
      the deduced amino acids sequence showed 74.4% identity with phospholipase gene
      (lec) from V. cholerae El Tor. The entire ORF of phospholipase gene was amplified
      by PCR and inserted into an Escherichia coli expression vector, pET22b(+) and
      introduced E. coli BL21(DE3). SDS-PAGE demonstrated that a protein corresponding
      to the phospholipase was overexpressed and migrated at a molecular mass of 53
      kDa.

PMID- 9767129
TI  - Quantification of a neurotrophin receptor from submilligram quantities of brain
      tissue using western blotting.
AB  - The immunodensity of the trkB neurotrophin receptor was quantified from
      submilligram quantities of brain tissue, using approximately 500 microgram
      samples dissected from the cochlear nucleus (CN) of adult guinea pigs. Tissue
      samples were hand-homogenized in a lysis buffer. After complete lysis, an aliquot
      of the lysate was taken to measure total protein, and the remainder was
      denatured. Proteins in the denatured aliquot were separated by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and electrophoretically
      transferred onto an immoblin-P membrane. The membrane was exposed to rabbit anti
      trkB and then to anti-rabbit IgG HRP conjugate. The immuno-complex on the
      membrane was detected by chemiluminescence, which was recorded on
      autoradiographic film. Autoradiographs were scanned into a computer and the trkB
      immunobands were quantified by densitometry. This procedure allowed the
      quantitative comparison of trkB neurotrophin receptor immunodensities between
      tissue samples. The procedure can be applied to the analysis of small samples of
      tissue collected from different brain regions or collected from the same region
      at different times, such as during development or aging, after administering a
      drug, or after placing a lesion.

PMID- 9767130
TI  - Palmitoylation of rhodopsin with S-protein acyltransferase: enzyme catalyzed
      reaction versus autocatalytic acylation.
AB  - Protein palmitoylation in vitro was studied using bovine rhodopsin as the
      substrate and a partially purified acylating enzymatic activity (PAT) from
      placental membranes. PAT incorporates fatty acid into rhodopsin with higher
      efficiency (10 times higher initial rate), as compared to autoacylation. The
      activity is sensitive to heat and trypsin, indicating a protein-mediated
      enzymatic process and requires the native conformation of rhodopsin. The presence
      of deacylated, free cysteine residues in dark-adapted rhodopsin increases
      palmitoylation via PAT. The sites for non-enzymatic and enzymatic palmitoylation
      could not be distinguished by peptide mapping. The reversible palmitoylation
      described here will provide a tool for the study of the role of palmitoylation in
      photoreceptor function.

PMID- 9767132
TI  - A fourth gene from the Candida albicans CDR family of ABC transporters.
AB  - Using primers derived from a region of the Candida albicans CDR1 (Candida drug
      resistance) gene that is conserved in other ABC (ATP-binding cassette)
      transporters, a DNA fragment from a previously unknown CDR gene was obtained by
      polymerase chain reaction (PCR). After screening a C. albicans genomic library
      with this fragment as a probe, the complete CDR4 gene was isolated and sequenced.
      CDR4 codes for a putative ABC transporter of 1490 amino acids with a high degree
      of homology to Cdr1p, Cdr2p and Cdr3p from C. albicans (62, 59 and 57% amino acid
      sequence identity, respectively). Cdr4p has a predicted structure typical for
      cluster I. 1 of yeast ABC transporters, characterized by two homologous halves,
      each comprising an N-terminal hydrophilic domain with consensus sequences for ATP
      binding and a C-terminal hydrophobic domain with six transmembrane helices. In
      contrast to the CDR1/CDR2 genes, the genetic structure of the CDR4 gene was
      conserved in 59 C. albicans isolates from six different patients. Northern
      hybridization analysis showed that the CDR4 gene was expressed in most isolates,
      but no correlation between CDR4 mRNA levels and the degree of fluconazole
      resistance of the isolates was found. In addition, a C. albicans mutant in which
      both copies of the CDR4 gene were disrupted by insertional mutagenesis was not
      hypersusceptible to fluconazole as compared to the parent strain. Unlike CDR1 and
      CDR2, CDR4 does not, therefore, seem to be involved in fluconazole resistance in
      C. albicans.

PMID- 9767131
TI  - Differential expression patterns of Wnt genes in the murine female reproductive
      tract during development and the estrous cycle.
AB  - The murine female reproductive tract differentiates during postnatal development.
      This process of cytodifferentiation and morphogenesis is dependent upon specific
      mesenchymal-epithelial interactions as well as circulating steroid hormones
      (Cunha, G.R., 1976. Int. Rev. Cytol. 47, 137-194; Pavlova, A. et al., 1994.
      Development 120, 335-346). Members of the Wnt family of signaling molecules have
      been recently identified in this system (Pavlova, A. et al., 1994. Development
      120, 335-346; Bui, T.D. et al., 1997. Br. J. Cancer 75, 1131-1136; Miller, C.,
      Sassoon, D.A., 1998. Development, in press). We describe the expression patterns
      of Wnt genes in the developing and adult female reproductive tract. Additionally,
      we note that changes in the levels of expression occur during the estrous cycle.
      Wnt gene expression patterns are regulated by the presence of epithelium in
      tissue graft experiments, suggesting that Wnt genes may indeed play roles in the
      mesenchymal-epithelial interactions critical for female reproductive tract
      development and function.

PMID- 9767133
TI  - Asymmetrical membrane fluidity of bovine adrenal chromaffin cells and granules
      and effect of trichosporin-B-VIa.
AB  - We examined membrane fluidity of bovine adrenal chromaffin cells and chromaffin
      granules using cationic trimethylammonium derivative of diphenylhexatriene (TMA
      DPH) as a fluorescence probe. After adding TMA-DPH to the suspension of
      chromaffin cells and that of granules, it first bound to the outer layer of the
      plasma membrane of the cells and that of the granule membrane, then gradually
      penetrated the inner layer of each membrane and distributed to both leaflets of
      the respective membranes. Accompanying increases in the ratio of incorporated
      probe on the cytoplasmic side of the chromaffin cell membrane, its fluorescence
      anisotropy gradually decreased. However, in chromaffin granules, the fluorescence
      anisotropy gradually increased with increases in the ratio of incorporated probe.
      These findings suggest that the inner layer of the plasma membrane and outer
      layer of the granular membrane are more fluid than the corresponding side of each
      membrane, which is suitable for the fusion between both membranes. We also
      examined the effect of trichosporin-B-VIa, a fungal ion channel forming alpha
      aminoisobutyric acid-containing peptide, on the fluidity of chromaffin cells
      using TMA-DPH. The peptide decreased the fluorescence anisotropy and increased
      the fluorescence intensity in the concentration range that induced Ca2+ dependent
      catecholamine secretion, suggesting that a change in lipid dynamics of the lipid
      bilayer of the plasma membrane was induced by this peptide.

PMID- 9767134
TI  - A mobile intracellular microelectrode designed to record from neurons in
      contracting tissue.
AB  - Intracellular recording from neurons in moving tissue allows data to be gathered
      in circumstances that are physiologically more realistic than those requiring
      pharmacological or mechanical suppression of movement. The construction of a
      mobile, suspended microelectrode assembly is described. Short glass
      microelectrodes were attached to a flexible length of 100 micrometer silver wire.
      A finer wire was inserted in the shank of the microelectrode to carry the
      electrical signal. Recordings were made from myenteric neurons of the guinea pig
      ileum, which was moving during the recording session. Intracellular recordings
      were maintained while the electrodes followed movements of 1 mm or more.

PMID- 9767135
TI  - Characterization of the gene for human EMMPRIN, a tumor cell surface inducer of
      matrix metalloproteinases.
AB  - EMMPRIN (extracellular matrix metalloproteinase inducer) also known as CD147 and
      basigin, is a member of the immunoglobulin family that is present on the surface
      of tumor cells and stimulates nearby fibroblasts to synthesize matrix
      metalloproteinases. Using our EMMPRIN cDNA, we have isolated a cosmid clone that
      contains the human EMMPRIN gene. S1 analysis with a fragment of the gene clone
      and primer extension of the mRNA was performed to determine the transcription
      start site. PCR and sequence analysis have defined the exon/intron organization
      of the gene and show that it is highly conserved with the mouse EMMPRIN/basigin
      gene. About 950 bases of the 5'-flanking region were examined for transcription
      factor consensus binding sites, locating three SP1 sites and two AP2 sites. The
      transcription start site was found to be located in a CpG island. Elements in the
      proximal promoter region were conserved in the human and mouse genes.

PMID- 9767136
TI  - Micelle formation of sodium cholate and solubilization into the micelle.
AB  - The micellization of sodium cholate (NaC) was studied at 298.2 K by aqueous
      solubility at different pH values. Using a stepwise association model of cholate
      anions without the sodium counterion, the aggregation number (n) of the cholate
      micelle was evaluated and found to increase with the total concentration,
      indicating that the mass action model worked quite well. The n value at 60 mM was
      found equal to 16. The membrane potential measurement of sodium ion with a cation
      exchange membrane was made in order to confirm the low counterion binding to
      micelle. The solubilization of alkylbenzenes (benzene, toluene, ethylbenzene, n
      propylbenzene, n-butylbenzene, n-pentylbenzene, n-hexylbenzene) and polycyclic
      aromatic compounds (naphthalene, anthracene, pyrene) into the aqueous micellar
      solution of sodium cholate was carried out. Solubilizate concentrations at
      equilibrium were determined spectrophotometrically at 298.2 K. The first stepwise
      association constants (K1) between solubilizate monomer and vacant micelle were
      evaluated from the equilibrium concentrations and found to increase with
      increasing hydrophobicity of the solubilizate molecules. From the Gibbs energy
      change for solubilization at the different mean aggregation numbers and from
      molecular structure of the solubilizates, the function of sodium cholate micelle
      for solubilization was discussed and was compared with data from conventional
      aliphatic micelles.

PMID- 9767137
TI  - Cognitive dysfunction and histological findings in rats with chronic-stage
      contusion and diffuse axonal injury.
AB  - The Morris water maze (MWM) technique is well known as a prominent method of
      evaluating learning acquisition and memory retention impairments in rats. We
      previously reported on a modified fluid percussion device that is able to
      consistently produce experimental cortical contusion (CC) and diffuse axonal
      injury (DAI) in separate groups of rats. The purpose of the present protocol is
      to evaluate the differences in learning acquisition and memory retention
      impairments between these two types of injured rats in the chronic stage using
      the MWM technique. CC and DAI rats are respectively induced by lateral and
      midline fluid percussion. We also compare the histological differences between
      these two different types of traumatic brain injury. The results show
      statistically significant differences in learning acquisition impairment between
      the sham and CC rats and between the sham and DAI rats. However, a difference in
      memory retention impairment was expected to be seen only between the sham and DAI
      rats. Histologically, the loss of CA3 pyramidal cells in the hippocampus was
      observed ipsilaterally in the CC and bilaterally in DAI. Neuronal cell loss was
      observed in bilaterally in layer II of the entorhinal cortex in DAI, but not in
      CC.

PMID- 9767138
TI  - Role of sonic hedgehog in branchiomotor neuron induction in zebrafish.
AB  - The role of zebrafish hedgehog genes in branchiomotor neuron development was
      analyzed by examining mutations that affect the expression of the hedgehog genes
      and by overexpressing these genes in embryos. In cyclops mutants, reduction in
      sonic hedgehog (shh) expression, and elimination of tiggy-winkle hedgehog (twhh)
      expression, correlated with reductions in branchiomotor neuron populations.
      Furthermore, branchiomotor neurons were restored in cyclops mutants when shh or
      twhh was overexpressed. These results suggest that Shh and/or Twhh play an
      important role in the induction of branchiomotor neurons in vivo. In sonic-you
      (syu) mutants, where Shh activity was reduced or eliminated due to mutations in
      shh, branchiomotor neurons were reduced in number in a rhombomere-specific
      fashion, but never eliminated. Similarly, spinal motor neurons were reduced, but
      not eliminated, in syu mutants. These results demonstrate that Shh is not solely
      responsible for inducing branchiomotor and spinal motor neurons, and suggest that
      Shh and Twhh may function as partially redundant signals for motor neuron
      induction in zebrafish.

PMID- 9767139
TI  - Characterization of a heat modifiable protein, Escherichia coli outer membrane
      protein OmpA in binary surfactant system of sodium dodecyl sulfate and
      octylglucoside.
AB  - A membrane protein, OmpA of Escherichia coli, in the process of refolding from
      its heat-modified form in the presence of sodium dodecyl sulfate (SDS) to its non
      heated one by the addition of systematic amounts of octylglucoside (OG) was
      characterized by means of dynamic light scattering and the size exclusion
      chromatography combined with low angle laser light scattering photometry. Upon
      heating in the presence of SDS only, the amount of SDS bound to OmpA was
      increased from 1.8 to 2.3 g/g of protein and its hydrodynamic radius increased
      from 3.7 to 4.7 nm. On the addition of OG, the once denatured OmpA regained its
      original size above the weight fraction of OG in the total amount of surfactants,
      0.8. During the process, the hydrodynamic radius was observed to decrease
      cooperatively at the weight fraction of 0.6, while no change took place in the
      molar mass of the protein. The refractive index increment of OmpA reflecting the
      amount of surfactant binding also regained the value before the heating in
      parallel with the change of size. Examination of the amount of surfactants bound
      to the membrane protein according to known properties of the binary surfactant
      micellar system of the surfactants showed that SDS was principally responsible
      for the denaturing phenomena of OmpA.

PMID- 9767140
TI  - Using GADlacZ transgenic mice as a marker system for homotopic transplantation.
AB  - Olfactory bulb (OB) transplantation is a well characterized model that has been
      widely used for studying neuronal plasticity and regeneration [G. Sekerkova, Z.
      Katarova, E. Mugnaini, F. Joo, J.R. Wolff, S. Prodan, G. Szabo, Intrinsically
      labeled relay neurons of homotopic olfactory bulb transplants establish proper
      afferent and afferent synaptic connections with host neurons, Neuroscience, 80
      (1997) 973-979 [10]; G. Sekerkova, Z. Malatova, J. Orendacova, T. Zigova,
      Transplantation of dorsal root ganglion into the olfactory bulb of neonatal rats:
      a histochemical study, Restor. Neurol. Neurosci., 6 (1993) 1-8 [11]; E. Racekova,
      I. Vanicky, T. Zigova, Correlation of functional alteration with lesion extent
      after olfactory bulbectomy in rats, Int. J. Neurosci., 79 (1994) 13-20 [12]; T.
      Zigova, P.P.C. Graziadei, A.G. Monti Graziadei, Olfactory bulb transplantation
      into the olfactory bulb of neonatal rats: an autoradiographic study, Brain Res.,
      539 (1991) 51-58 [13]]. In previous studies, the OB grafts have been routinely
      labeled by tritiated thymidine [S.M. Onifer, L.A. White, S.R. Whittemore, V.R.
      Holets, In vitro labelling strategies for identifying primary neural tissue and
      neuronal cell line after transplantation in the CNS, Cell Transplant., 2 (1993)
      131-149 [7]; [13]] allowing distinction of graft from the surrounding tissue by
      the presence of silver grains over the cell nuclei of the transplant. However,
      this approach has some disadvantages, namely: partial or insufficient labeling of
      a defined neuronal subclasses due to the length of the period of their
      generation, variation in the number of labeled cells due to differences in the
      gestation stage between individual embryos at the time of i.p. injection of
      tritiated thymidine, inability to follow the dendritic arborization and axonal
      outgrowth of the transplanted neurons or to detect directly their actual synaptic
      contacts, and finally, the need to work with radioactive isotopes. In this paper,
      we describe an alternative approach, in which the donor OBs in a homotopic OB
      transplantation were derived from transgenic mice carrying the bacterial gene
      lacZ under control from the regulatory region of GAD67 gene. In these mice, beta
      galactosidase (beta-gal), encoded by lacZ is stably, ectopically expressed in the
      vast majority of mitral/tufted (M/T) cells of the OB and served as their
      intrinsic cellular marker in the OB transplant. By using a simple histochemical
      reaction for beta-gal or immunocytochemistry with anti-beta-gal antibody, we
      could detect the cell bodies and processes of the donor M/T cells and their
      synaptic contacts with host neurons after long-term survival using both light and
      electron microscopy. Given the great number of existing transgenic mouse lines
      that express in the nervous system, this approach may have an even wider
      application in neural transplantation.

PMID- 9767141
TI  - NCL1, a novel gene for a non-essential nuclear protein in Saccharomyces
      cerevisiae.
AB  - The nucleolar protein Nop2p is an essential gene product that is required for pre
      rRNA processing and ribosome biogenesis in Saccharomyces cerevisiae (Hong, B. et
      al., 1997, Mol. Cell. Biol., 17, 378-388). A search for proteins similar to Nop2p
      identified a novel yeast gene product that also shares significant homology with
      the human proliferation associated nucleolar protein p120. The gene encoding this
      78kDa protein was termed NCL1 (for nuclear protein 1; corresponding to YBL024w).
      Ncl1p and Nop2p contain an evolutionarily conserved motif that has been termed
      the 'NOL1/NOP2/fmu family signature' (NOL1 encodes p120). Epitope tagged Ncl1p
      was found to be localized to the nucleus, including the nucleolus, and was
      concentrated at the nuclear periphery. NCL1 is not essential. Strains containing
      a disruption of NCL1, or strains overexpressing NCL1, grow essentially
      identically to wildtype NCL1 strains on a number of different media and at
      different temperatures. Disruption of NCL1 does not affect steady-state levels of
      large and small ribosome subunits, monoribosomes, and polyribosomes. However,
      disruption of NCL1 leads to increased sensitivity to the antibiotic paromomycin.

PMID- 9767142
TI  - Unmyristoylated MARCKS-related protein (MRP) binds to supported planar
      phosphatidylcholine membranes.
AB  - We have recently shown that unmyristoylated MARCKS-related protein (MRP) does not
      bind to neutral phospholipid vesicles, unless negatively charged phospholipids
      are present. Similar behaviour has also been reported for MARCKS itself. Here we
      have compared the binding of MRP to neutral and negatively charged supported
      planar lipid bilayer membranes (SPLM) using two-mode waveguide spectroscopy. We
      find appreciable binding of unmyristoylated MRP to neutral SPLM. We propose that
      hydrophobic residues in the effector domain constitute an additional factor
      capable of mediating MRP-membrane interaction.

PMID- 9767143
TI  - Inositol polyphosphates regulate the membrane interactions of the endosomal p100,
      G-protein-related protein.
AB  - The protein, p100, was previously identified as a G-protein related protein that
      cycles on and off the cytoplasmic face of the endosome membrane (Traub et al.,
      Biochem. J. 280 (1991) 171-178). Here we present evidence that the inositol
      polyphosphates, inositol 1,4, 5-trisphosphate (IP3) and inositol hexakisphosphate
      (IP6), release p100 from light-density microsomal membranes and inhibit rebinding
      of p100 through receptors, which are specific for IP3 or for IP6. These receptors
      can be co-extracted with p100 from the microsomes by 0.5 M Tris-HCl and, in the
      soluble state, they exhibit similar binding activity towards the inositol
      polyphosphates as do untreated microsomes. Soluble p100 self-aggregates and this
      aggregation is blocked by both IP3 and IP6. Stimulation of permeabilized rat
      basophilic leukemia (RBL-2H3) cells with carbachol, via transfected muscarinic m1
      receptors, results in increased levels of inositol polyphosphates and the
      quantitative release of p100 into the cytosol. This effect is reversible and
      cytosolic p100 rebinds to the membrane as the levels of inositol polyphosphates
      decline. These findings suggest that p100 may belong to a family of IP-binding
      proteins whose intracellular localization is determined by extracellular signals.

PMID- 9767144
TI  - A Ca2+- and voltage-dependent cation channel in the nuclear envelope of red beet.
AB  - The patch-clamp technique was applied to study ion conductances in various
      configurations of the nuclear envelope of non-enzyme-treated red beet (Beta
      vulgaris L.) nuclei. With excised patches a non-selective cation channel was
      observed, that was activated by micromolar concentrations of Ca2+ on the
      nucleoplasmic side of the envelope. The channel activity was also voltage
      dependent and the voltage threshold of channel activation changed with the
      nucleoplasmic Ca2+ concentration. The most prominent conductance level was 110+/
      22 pS with 150 mM KCl in the bath and pipette. The channel was permeable to small
      cations: permeabilities relative to K+ were PK congruent with PNa=1, PCs=0.3, but
      PCl=0.09. Calcium ions also permeated the channel with PCa=0.43, estimated from
      reversal potential, or 0.14, estimated from conductance ratio. Zn2+ (1 mM) when
      applied to the cytoplasmic side of the envelope blocked the channel activity
      completely, while amiloride (2 mM) reduced the channel current by 86% from the
      nucleoplasmic side. The properties of the whole-nucleus current (voltage-, time-
      and Ca2+-dependence) paralleled those observed with excised patches. The channel
      may provide a Ca2+-regulated pathway for passive diffusion of cations across the
      nuclear envelope and thus may play an important role in Ca2+-dependent nuclear
      processes ranging from gene transcription to apoptosis.

PMID- 9767145
TI  - The specificity of proneural genes in determining Drosophila sense organ
      identity.
AB  - The proneural genes (atonal and the genes of the achaete-scute complex (AS-C))
      are required for the selection of sense organ precursors. They also endow these
      precursors with sense organ subtype information. In most of the ectoderm, atonal
      is required for precursors of chordotonal sense organs, whereas AS-C are required
      for those of most external sense organs, such as bristles. To address the
      question of how proneural genes influence subtype identity, we have made use of
      the Gal4/UAS system of misexpression. Unlike previous misexpression experiments,
      we found that under specific conditions of misexpression, atonal shows high
      subtype specificity of ectopic sense organ formation. Moreover, atonal can even
      transform wild-type external sense organs to chordotonal organs, although scute
      cannot perform the reciprocal transformation. Our evidence demonstrates that
      atonal's subtype determining role is not to activate directly chordotonal fate,
      but to repress the activation of cut, a gene that is necessary for external sense
      organ fate, thereby freeing its precursors to follow the alternative chordotonal
      organ fate.

PMID- 9767146
TI  - A unique amyloidogenic apolipoprotein serum amyloid A (apoSAA) isoform expressed
      by the amyloid resistant CE/J mouse strain exhibits higher affinity for
      macrophages than apoSAA1 and apoSAA2 expressed by amyloid susceptible CBA/J mice.
AB  - CBA/J and other inbred strains of mice that express the amyloidogenic
      apolipoprotein serum amyloid A (apoSAA) apoSAA2, together with apoSAA1, are
      susceptible to amyloid A (AA) amyloidosis, whereas CE/J mice that express a
      single unique isoform, apoSAACEJ, are resistant. Studies indicate that CBA/JxCE/J
      hybrid mice that express apoSAA2 in the presence of apoSAACEJ are protected from
      amyloidogenesis. To define a mechanism by which expression of apoSAACEJ may
      protect from AA formation in the presence of apoSAA2, binding of recombinant
      apoSAA (r-apoSAA) isoforms, validated by N-terminal sequencing, to a murine
      macrophage cell line was investigated. Maximal specific binding occurred after
      incubation of radiolabeled apoSAA with IC-21 macrophages (1x105 cells/ml) for 30
      min at 4 degreesC. The binding of 125I-r-apoSAA1, 125I-r-apoSAA2 and 125I-r
      apoSAACEJ was specific and saturable, with an affinity (Kd) of about 2.8, 3.2 and
      1.3 nM, respectively, and approximately 2-4x106 sites per cell. Competitive
      binding experiments indicate apoSAACEJ binds with higher affinity to macrophages
      than does either apoSAA1 or apoSAA2. We suggest that greater cellular affinity of
      apoSAACEJ compared to apoSAA2 may contribute to protection from AA amyloid in
      certain CBA/JxCE/J hybrid mice by interfering with interaction of apoSAA2 by
      macrophages and hence either membrane associated or intracellular degradation.

PMID- 9767148
TI  - Nitric oxide reduces hypophagia induced by threonine free diet in the rat.
AB  - Food intake and concentrations of glutamic (GLU) and aspartic (ASP) acids in the
      nucleus accumbens were monitored in male Sprague-Dawley rats fed a threonine free
      diet. These variables were measured before and after an intracerebroventricular
      injection of 20 nmole nitroprusside (NP), a non-enzymatic nitric oxide donor. The
      same variables were also monitored in: (a) rats fed a threonine free diet and
      injected with saline; (b) animals fed a standard diet and injected with
      nitroprusside; (c) rats fed a standard diet and injected with saline. The results
      showed that the threonine-free diet reduced food intake and GLU and ASP
      concentrations in the accumbens. NP reduced the hypophagia, but it did not change
      GLU and ASP levels in rats fed the threonine-free diet. In animals fed the
      standard diet, NP increased GLU and ASP concentration, and food intake. No change
      was found in the animals with saline injection. These findings suggest that
      nitric oxide reduces the hypophagia in the rats fed a threonine-free diet. The
      lack of increase in GLU and ASP concentration in the nucleus accumbens of the
      hypophagic rats indicates that NP acts on hypophagia independently by GLU and
      ASP.

PMID- 9767147
TI  - Characterization of platyhelminth POU domain genes: ubiquitous and specific
      anterior nerve cell expression of different epitopes of GtPOU-1.
AB  - POU domain proteins are a large family of transcription factors that have been
      identified in a variety of metazoans, from freshwater sponges, planarians and
      nematodes to arthropods, echinoderms and vertebrates. Many of these proteins are
      implicated in the development and establishment of the nervous system. In this
      paper we describe the identification of the planarian genes GtPOU-1, GtPOU-3 and
      GtPOU-4, which belong to the subclasses III and IV of POU-domain genes. Their
      similarity with other members of the POU family is restricted to the POU and
      homeo domains, plus some peptide sequences scattered in the linker and flanking
      regions. As with other subclass III POU genes, GtPOU-1 is devoid of introns.
      Axial transcript distribution by RT-PCR and immunohistochemical assays, performed
      with a polyclonal antibody raised against the GtPOU-1 fusion protein, indicate
      that both the GtPOU-1 transcript and protein are continuously expressed along the
      antero-posterior axis. A monoclonal antibody raised against the same fusion
      protein indicates that a GtPOU-1-specific epitope, probably obtained by post
      translational modification, is present in neural cells from both the central and
      peripheral nerve systems of the adult planarian's anterior third. Moreover, the
      GtPOU-1-specific epitope shows a dynamic expression pattern during regeneration,
      always marking the most anterior region of the planarian nervous system. Both the
      rapid and general GtPOU-1-specific epitope modification, during posterior
      regeneration, indicate that regeneration is a global process involving all
      planarian regions, including those that are far from the wound, by a combination
      of morphallactic and epimorphic mechanisms.

PMID- 9767149
TI  - Expression and regulation of the insulin-like growth factor-1 receptor by growing
      and quiescent H4IIE hepatoma.
AB  - Recent evidence that insulin-like growth factor-1 (IGF-1) influences certain
      properties of H4IIE hepatoma cells independent of insulin led us to examine
      whether H4IIE cells express IGF-1 receptors. Competitive binding experiments
      demonstrated IGF-1, but not insulin or IGF-II, could compete with [125I]IGF-1.
      Chemical crosslinking detected a protein with an apparent mass of 175 kDa and its
      identity as the IGF-1 receptor alpha-subunit was confirmed by Western blotting.
      The apparent molecular mass of this protein decreased to 135 kDa following
      deglycosylation. Immunofluorescence microscopy verified that both insulin and IGF
      1 receptors were present, although measurement of IGF-1 receptor quantity
      revealed they were less abundant than insulin receptors. Binding of IGF-1 was low
      in growing cells and higher in a quiescent cell population. Scatchard analysis
      confirmed that receptor density was increased in non-growing H4IIE cells while
      there was no apparent difference in receptor affinity. Western blot analysis and
      RT-PCR revealed that both protein and mRNA levels were elevated as cell growth
      ceased. Interestingly, addition of insulin to quiescent H4IIE cells, which
      stimulates cell proliferation, further increased IGF-1 receptor protein levels
      with a peak at 12-24 h. Distinct modes of regulating IGF-1 receptor expression
      are indicated.

PMID- 9767150
TI  - Norepinephrine release in the amygdala in response to footshock and opioid
      peptidergic drugs.
AB  - These experiments used in vivo microdialysis and high-performance liquid
      chromatography to examine, in rats, norepinephrine (NE) release in the amygdala
      induced by footshock and systemic administration of drugs affecting the opioid
      peptidergic system. A microdialysis probe was inserted into a previously
      implanted guide cannula aimed at the amygdala and the rat was placed in a box
      with a stainless-steel grid floor through which a single footshock was delivered.
      Samples were collected and analyzed at 15-min intervals. Footshock stimulation
      increased NE levels and the magnitude of the increase varied with footshock
      intensity. Relative to baseline levels, intensities of 0.3, 0.7 and 1.2 mA (3 s)
      induced increases of 41, 64 and 97%, respectively. NE levels returned to baseline
      within 30 min after footshock stimulation. The opioid peptidergic antagonist
      naloxone (1 mg/kg, i.p.) administered immediately after footshock (0.55 mA for 1
      s) potentiated NE release. In contrast, the opioid peptidergic agonist beta
      endorphin (10 microgram/kg, i.p.) administered after the footshock blocked the
      footshock-induced increase in NE levels. The magnitude of NE release was less
      when the drugs were administered without prior footshock and when the injections
      were given 30 min after footshock. The findings are consistent with previous
      evidence that acute, mildly stressful stimulation induces the release of NE in
      the amygdala as well as with extensive pharmacological evidence indicating that
      amygdala NE released by arousing stimulation is involved in regulating memory
      storage and that the opioid peptidergic system influences memory storage by
      modulating the release of NE in the amygdala.

PMID- 9767151
TI  - Sequence and mutational analysis of the devBCA gene cluster encoding a putative
      ABC transporter in the cyanobacterium Anabaena variabilis ATCC 29413.
AB  - The devBCA gene cluster (dev for development), shown to be essential for envelope
      formation in heterocysts of Anabaena sp. strain PCC 7120, was identified in the
      gene bank of a second heterocyst-forming strain, Anabaena variabilis ATCC 29413.
      Sequence and structural organization of the three genes, encoding subunits of a
      presumptive ABC transporter, were nearly identical in both strains. Mutants of A.
      variabilis defective in the devA gene were constructed. As devA mutants of
      Anabaena 7120, A. variabilis mutants were unable to grow on N2 as sole nitrogen
      source due to incomplete differentiation of heterocysts.

PMID- 9767153
TI  - Craf-1 protein kinase is essential for mouse development.
AB  - The three mammalian Raf serine/threonine protein kinases mediate the transduction
      of proliferative and differentiative signals from a variety of cell surface
      receptors to the nucleus. We report here that Craf-1 is essential for mouse
      development, as its mutation results in embryonic lethality. Developmental
      defects are found in mutant placentas as well as in the skin and in the lungs of
      mutant embryos. Craf-1 mutants also display a generalized growth retardation
      which is consistent with the ubiquitous expression of Craf-1 and which could be
      due to the reduced proliferation of mutant cells. Interestingly, the time-point
      of embryonal death varies depending on the genetic background. This suggests that
      Craf-1-mediated signaling is affected by genetic background-specific alleles of
      other genes.

PMID- 9767152
TI  - Immunocytochemical localization of the NMDA-R2A receptor subunit in the cat
      retina.
AB  - Immunocytochemical studies were performed to determine the distribution and
      cellular localization of the NMDA-R2A receptor subunit (R2A) in the cat retina.
      R2A-immunoreactivity (R2A-IR) was noted in all layers of the retina, with
      specific localizations in the outer segments of red/green and blue cone
      photoreceptors, B-type horizontal cells, several types of amacrine cells, Muller
      cells and the majority of cells in the ganglion cell layer. In the inner nuclear
      layer, 48% of all cells residing in the amacrine cell layer were R2A-IR including
      a cell resembling the GABAergic A17 amacrine cell. Interestingly, the AII rod
      amacrine cell was devoid of R2A-IR. Although the localization of the R2A subunit
      was anticipated in ganglion cells, amacrines and Muller cells, the presence of
      this receptor subunit to the cells in the outer retina was not expected. Here,
      both the R2A and the R2B subunits were found to be present in the outer segments
      of cone photoreceptors and to the tips of rod outer segments. Although the
      function of these receptor subunits in rod and cone photoreceptors remains to be
      determined, the fact that both R2A and R2B receptor subunits are localized to
      cone outer segments suggests a possible alternative pathway for calcium entry
      into a region where this cation plays such a crucial role in the process of
      phototransduction. To further classify the cells that display NR2A-IR, we
      performed dual labeling experiments showing the relationship between R2A-labeled
      cells with GABA. Results showed that all GABAergic-amacrines and displaced
      amacrines express the R2A-subunit protein. In addition, approximately 11% of the
      NR2A-labeled amacrines, did not stain for GABA. These findings support
      pharmacological data showing that NMDA directly facilitates GABA release in
      retina and retinal cultures [I.L. Ferreira, C.B. Duarte, P.F. Santos, C.M.
      Carvalho, A.P. Carvalho, Release of [3H]GABA evoked by glutamate receptor agonist
      in cultured chick retinal cells: effect of Ca2+, Brain Res. 664 (1994) 252-256;
      G.D. Zeevalk, W.J. Nicklas, Action of the anti-ischemic agent ifenprodil on N
      methyl-d-aspartate and kainate-mediated excitotoxicity, Brain Res. 522 (1990) 135
      139; R. Huba, H.D. Hofmann, Transmitter-gated currents of GABAergic amacrine-like
      cells in chick retinal cultures, Vis. Neurosci. 6 (1991) 303-314; M. Yamashita,
      R. Huba, H.D. Hofmann, Early in vitro development of voltage- and transmitter
      gated currents in GABAergic amacrine cells, Dev. Brain Res. 82 (1994) 95-102; R.
      Ientile, S. Pedale, V. Picciurro, V. Macaione, C. Fabiano, S. Macaione, Nitric
      oxide mediates NMDA-evoked [3H]GABA release from chick retina cells, FEBS Lett.
      417 (1997) 345-348; R.C. Kubrusly, M.C. deMello, F.G. deMello, Aspartate as a
      selective NMDA agonist in cultured cells from the avian retina, Neurochem. Intl.
      32 (1998) 47-52] or reduction of GABA in vivo [N.N. Osborn, A.J. Herrera, The
      effect of experimental ischaemia and excitatory amino acid agonist on the GABA
      and serotonin immunoreactivities in the rabbit retina, Neurosci. 59 (1994) 1071
      1081]. Since the majority of GABAergic synapses in the inner retina are onto both
      rod and cone bipolar axon terminals [R.G. Pourcho, M.T. Owzcarzak, Distribution
      of GABA immunoreactivity in the cat retina: A light and electron-microscopic
      study, Vis. Neurosci. 2 (1989) 425-435], we hypothesize that the NMDA-receptor
      plays a crucial role in providing feedback inhibition onto rod and cone bipolar
      cells.

PMID- 9767154
TI  - Expression of the homeobox gene GBX2 during chicken development.
AB  - We have examined the expression pattern of the GBX2 gene during chicken
      embryogenesis. First transcripts are found in the epiblast of a HH st. 3+ embryo.
      With the onset of neurogenesis, transcripts mark the posterior neuroectoderm.
      Later on, expression is detectable in the isthmic region, the hindbrain and the
      neural tube. We show that GBX2 transcripts, as well as the protein, mark the
      presumptive hindbrain region. After establishment of the brain vesicles GBX2
      transcripts were also detected in distinct domains of the diencephalon. In
      addition to neural sites of expression, GBX2 was found in several domains
      including the otic vesicle, the somitic mesoderm, the lateral foregut endoderm,
      the ventral limb bud ectoderm and in the feather buds.

PMID- 9767155
TI  - Selective in vivo fluorescence labelling of cholinergic neurons containing
      p75(NTR) in the rat basal forebrain.
AB  - The cholinergic system of the rat basal forebrain is used as a model for the
      homologous region in humans which is highly susceptible to neuropathological
      alterations as in Alzheimer's disease. Cholinergic cells in the basal forebrain
      express the low-affinity neurotrophin receptor p75NTR. This has been utilized for
      selective immunolesioning of cholinergic neurons after internalization of an
      immunotoxin composed of anti-p75NTR and the ribosome-inactivating toxin saporin.
      However, the goal of many studies may be not the lesion, but the identification
      of cholinergic cells after other experimentally induced alterations in the basal
      forebrain. Therefore, a novel cholinergic marker was prepared by conjugating the
      monoclonal antibody 192IgG directed against p75NTR with the bright red
      fluorochrome carbocyanine 3 (Cy3). Three days after intraventricular injection of
      Cy3-192IgG the fluorescence microscopic analysis revealed a pattern of Cy3
      labelled cells matching the distribution of cholinergic neurons. Apparently the
      marker was internalized within complexes of p75NTR and Cy3-192IgG which were then
      retrogradely transported to the cholinergic perikarya of the basal forebrain. In
      addition to the even labelling of somata, a strong punctate-like Cy3
      immunofluorescence was seen in structures resembling lysosomes. The specificity
      of the in vivo staining was proven by subsequent immunolabelling of choline
      acetyltransferase (ChAT) with green fluorescent Cy2-tagged secondary antibodies.
      In the medial septum, the diagonal band and the nucleus basalis only cholinergic
      neurons were marked by Cy3-192IgG. In parallel experiments, digoxigenylated
      192IgG was not detectable within cholinergic basal forebrain neurons after
      intraventricular injection. Presumably, this modified antibody could not be
      internalized. On the other hand, digoxigenylated 192IgG was found to be an
      excellent immunocytochemical marker for p75NTR as shown by double labelling
      including highly sensitive mouse antibodies directed against ChAT. Based on the
      present findings, future applications of the apparently non-toxic Cy3-192IgG and
      other antibodies for fluorescent in vivo and in vitro labelling are discussed.

PMID- 9767156
TI  - Expression of Gbx-2 during early development of the chick embryo.
AB  - Gbx-2 is required for the normal development of the anterior hindbrain. Since
      much of our understanding of the normal development of this region derives from
      studies of avian embryos, we have determined the expression of Gbx-2 in chick
      embryos at stages relevant to the regionalization of the hindbrain. As the neural
      plate forms transcripts already have a clear anterior limit of expression and,
      subsequently, occupy a domain extending from the extreme posterior midbrain to
      the rhombomere 3/4 boundary. Subsequently, expression is restricted to the
      isthmus, a dorsal stripe of expression extending throughout the hindbrain in the
      ventricular region and the cells adjacent to rhombomere boundaries. Transcripts
      were also detected in pharyngeal endoderm, the otic placode and vesicle,
      pharyngeal arches and somites.

PMID- 9767157
TI  - Maternally localized RNA encoding a serine/threonine protein kinase in the
      ascidian, Halocynthia roretzi.
AB  - Maternally localized cytoplasmic determinants play important roles in the
      embryogenesis of many animals, including ascidians. Cytoplasmic determinants are
      particularly important in the determination of cell fates, and in the
      establishment of the embryonic axes. Ascidians, which show mosaic development,
      are good models for the study of maternal cytoplasmic determinants. Here we
      report the isolation and characterization of HrPOPK-1 (Halocynthia roretzi
      posterior protein kinase-1), a putative protein serine/threonine kinase. HrPOPK-1
      cDNA was obtained from a Halocynthia roretzi fertilized egg cDNA library by
      screening for localized RNAs using whole-mount in situ hybridization. HrPOPK-1
      mRNA is strongly localized at the posterior pole of embryos. The pattern of
      HrPOPK-1 mRNA localization during early embryogenesis is identical to that of
      HrWnt-5 in Halocynthia roretzi, and to those of the posterior end mark (pem)
      transcripts of Ciona savignyi. In addition, HrPOPK-1 shows zygotic expression in
      neural tissues at the tailbud stage. These results show that the temporal
      regulation of HrPOPK-1 transcription is complex.

PMID- 9767158
TI  - Anti-opioid efficacy of neuropeptide FF in morphine-tolerant mice.
AB  - The modulatory effects of 1DMe (d-Tyr-Leu-(NMe)Phe-Gln-Pro-Gln-Arg-Phe-NH2), an
      agonist of Neuropeptide FF (NPFF) receptors, on opioid antinociceptive activity
      have been compared in naive and tolerant mice in the tail-flick and the hot-plate
      tests. In naive mice, 1DMe alone had no effect on pain threshold but decreased
      dose-dependently (3-22 nmol) the analgesic activity of morphine in both tests. In
      tolerant mice, injections of 60-fold lower doses of 1DMe (0.05-0.5 nmol) reverse
      morphine-induced analgesia in the tail-flick test but this anti-opioid effect was
      no longer observed with the highest doses of 1DMe tested (3-22 nmol). In the hot
      plate test, the anti-opioid action of 1DMe was not detected, whatever doses
      tested. Neither the NPFF-like immunoreactivity content of spinal cord and of
      olfactory bulbs, nor the density of NPFF receptors in olfactory bulbs, were
      altered. These results indicate that a chronic morphine treatment modifies the
      pharmacological properties of NPFF but the type of pain test is crucial in
      determining NPFF effects.

PMID- 9767159
TI  - Expression pattern of the winged helix factor XFD-11 during Xenopus
      embryogenesis.
AB  - We have identified a cDNA encoding a novel Xenopus winged helix transcription
      factor termed as XFD-11 (Xenopus fork head domain). The DNA binding domain is
      most closely related to those of human or murine FREAC-3 (FKHL7/MF-1/FKH-1)
      proteins. The XFD-11 gene is activated at late blastula/early gastrula and
      transcription proceeds throughout embryogenesis. Early expression is found in
      ventral and lateral but not in dorsal mesoderm. At neurula stages, transcripts
      are found in posterior mesoderm except for the dorsal midline, and the gene is
      also transcribed at the lateral border of the neural plate and within anterior
      neuroectoderm. At later stages of development, transcripts are detected within
      the pronephros, the heart, within neural crest cells surrounding the eye, in the
      mandibular, hyoid and branchial arches, and within the tail.

PMID- 9767160
TI  - Contribution of dopamine neurons in the medial zona incerta to the innervation of
      the central nucleus of the amygdala, horizontal diagonal band of Broca and
      hypothalamic paraventricular nucleus.
AB  - Results of previous studies suggested that incertohypothalamic dopamine (IHDA)
      neurons located in the medial zona incerta (MZI) project to the central nucleus
      of the amygdala (cAMY), horizontal diagonal band of Broca (HDB), and
      paraventricular nucleus (PVN). The overall goal of the present study was to
      determine the relative contribution of IHDA neurons to the DA innervation of
      these brain regions. A combined fluorescent and in situ hybridization
      histochemical procedure was employed to localize the retrograde tracer fluoro
      gold (FG) in cells expressing tyrosine hydroxylase (TH) mRNA in the MZI following
      its iontophoretic injection into either the cAMY, HDB or PVN. For comparison, the
      numbers of dual labeled FG/TH mRNA neurons in the midbrain were also determined.
      One week after unilateral injection of FG into the cAMY, cells containing FG+TH
      mRNA were found in the ipsilateral MZI, substantia nigra zona compacta (SNC) and
      ventral tegmental area (VTA). The total numbers of cells labeled with FG varied
      with the size of the injection site, but the ratio of dual labeling in the MZI to
      that of the SNC-VTA remained constant across animals at approximately 1:6. FG
      injections into the HDB resulted in a ratio of dual labeled cells in the
      ipsilateral MZI and VTA of approximately 1:2, but no dual labeled cells were
      found in the SNC. Dual labeled cells were only found in the ipsilateral MZI in
      animals receiving FG injections in the PVN. Thus, DA terminals in the PVN
      originate exclusively from IHDA neurons in the MZI, whereas these neurons provide
      only a portion of the DA innervation of the cAMY and HDB. The similar
      distribution of dual labeled cells in the MZI following FG injections into the
      cAMY, HDB and PVN suggests that perikarya of IHDA neurons projecting to these
      regions are not organized into distinct groups.

PMID- 9767161
TI  - Restricted expression of the homeobox gene prox 1 in developing zebrafish.
AB  - Prox 1 is a vertebrate homeobox gene which is homologous to the Drosophila
      transcription factor, prospero. We have isolated a prox 1 cDNA from zebrafish,
      which encodes a protein that has 82%, 84% and 83% amino acid identity with
      chicken, mouse and human Prox 1, respectively. Antibodies raised against human
      Prox 1 cross-react with zebrafish Prox 1 and are used here to determine the
      expression patterns of Prox 1 during zebrafish embryogenesis by whole-mount
      immunohistochemistry. In the 10-somite embryo, Prox 1 is expressed over the
      prospective lens placode and over a broad region of epithelium extending from the
      eye to the otic vesicle. As embryogenesis proceeds, Prox 1 expression in the eye
      lens becomes intense, and is detected in maturing muscle pioneer cells and
      superficial muscle cells. In the CNS, Prox 1 is expressed in a stripe along the
      forebrain-midbrain boundary, in a segmented pattern in the ventral hindbrain, and
      in selected cells of the ventral spinal cord. Additional sites of Prox 1
      expression include the lateral line primordium, the trigeminal ganglia, the otic
      vesicle and occasional endodermal cells.

PMID- 9767162
TI  - Declines in stimulated striatal dopamine release over the first 32 h following
      microdialysis probe insertion: generalization across releasing mechanisms.
AB  - In a recent paper [R.R. Holson, J.F. Bowyer, P. Clausing, B. Gough,
      Methamphetamine-stimulated striatal dopamine release declines rapidly over time
      following microdialysis probe insertion, Brain Res. 739 (1996) 301-307] we
      reported that methamphetamine-stimulated striatal dopamine release declined
      rapidly over the first eight hours following microdialysis probe insertion. This
      decline was strictly a function of time post-probe implantation, and not due to
      tolerance or desensitization. To further examine this phenomenon, we subjected
      rats to three brief pulses of several DA-releasing compounds at 2, 4 and 6 h post
      probe insertion, and compared these results to those caused by a single pulse 6 h
      post-insertion, or in some cases to pulses given more than 24 h post-insertion.
      We found that when buproprion, a dopamine reuptake blocker, was infused briefly
      into the striatum via the microdialysis probe, there was a pronounced drop in the
      amount of dopamine released at 6 h vs. 2 h post-insertion; this drop was not due
      to repeated exposure, since dopamine release at 6 h post-insertion was the same
      for a single pulse, or when preceded by two earlier pulses. Twenty-four hours
      later, buproprion-stimulated dopamine release was still lower, but did not appear
      to drop further thereafter. Potassium-stimulated dopamine release, on the other
      hand, dropped rapidly over the first 8 h post-insertion, and this decline
      continued throughout the 24-32 h interval post-insertion. Similarly, a single
      i.p. injection of 0.5 mg/kg haloperidol released three times as much dopamine
      when given two compared to six hours post-implantation. Both bupropion- and
      potassium-stimulated dopamine release were accompanied by declines in
      extracellular DOPAC concentrations, and these declines were the same 2 or 26 h
      post-insertion. In contrast, haloperidol exposure increased extracellular DOPAC,
      and this haloperidol-stimulated DOPAC increase was also greatly attenuated at 6
      compared to 2 h post-insertion. We conclude that there is a general decline over
      time post-probe implantation in the ability of the striatal dopamine system to
      release dopamine, and perhaps to increase dopamine synthesis, in response to
      pharmacological challenges.

PMID- 9767163
TI  - The winged helix transcription factor Hfh2 is expressed in neural crest and
      spinal cord during mouse development.
AB  - The embryonic neural crest is a unique group of cells that gives rise to the
      peripheral nervous system as well as many other cell types. Most of the work
      describing the behavior and specification of these cells has been done in the
      avian system, a system amenable to experimental manipulations such as tissue
      grafting, cell transplantation and lineage tracing. This work has been greatly
      facilitated by the use of molecular markers of neural crest cells such as HNK-1
      and slug, markers that are not yet available for the study of mouse neural crest.
      Here we demonstrate that Hfh2 (HNF3 forkhead homologue 2), a member of the
      'winged helix' or 'forkhead' transcription factor gene family, is expressed in
      premigratory and migrating neural crest cells in the early mouse embryo and in
      motorneuron progenitors in the developing spinal cord. Using linkage analysis we
      have localized the Hfh2 gene to chromosome 4 at 44.91 cM from the centromere.

PMID- 9767164
TI  - Microsphere embolism-induced changes in noradrenaline uptake of the cerebral
      cortex in rats.
AB  - The present study was undertaken to elucidate pathophysiological changes in
      noradrenaline (NA) transporter and Na+/K+-ATPase, key regulators of cation
      gradient across the plasma membrane, in nerve terminals of the cerebral cortex
      after microsphere-induced cerebral embolism in rats. The Vmax value of NA uptake,
      when analyzed by the Eadie-Hofstee plot, tended to decrease on the 1st day and
      decreased on the 3rd and 7th days after the embolism without any change in the Km
      value. The NA content in cerebrocortical synaptosomes did not alter on the 1st
      day, but decreased on the 3rd and 7th days after the embolism. Ouabain (1 mM)
      inhibited NA uptake on the 1st day, but did not alter the uptake on the 3rd and
      7th days after the embolism. The activity of Na+/K+-ATPase of cerebrocortical
      synaptosomes increased on the 1st day and gradually decreased up to the 7th day
      after the embolim. These results suggest that NA uptake in nerve terminals of the
      cerebral cortex decreased after microsphere embolism, which may be due to a
      reduction in function of NA transporters. The changes in Na+/K+-ATPase following
      microsphere embolism may represent a compensatory action to maintain ion
      homeostasis in nerve terminals at an early stage of ischemic injury.

PMID- 9767165
TI  - musculin: a murine basic helix-loop-helix transcription factor gene expressed in
      embryonic skeletal muscle.
AB  - We describe the embryonic expression of musculin, a new murine member of the bHLH
      family of transcription factors. Musculin protein is closely related to human ABF
      1, which is expressed in activated B cells, and to epicardin/capsulin/Pod-1,
      which is expressed in branchial myoblasts, visceral and urogenital mesoderm and
      epicardium. In situ hybridisation revealed musculin expression in embryos was
      largely restricted to the embryonic skeletal muscle lineage. While all skeletal
      muscles expressed the gene, only a subset of myocytes within each muscle were
      positive, indicating molecular heterogeneity within fetal muscle.

PMID- 9767167
TI  - Amphioxus AmphiDRAL encoding a LIM-domain protein: expression in the epidermis
      but not in the presumptive neuroectoderm 
AB  - The sequence and developmental expression have been determined for amphioxus
      AmphiDRAL, which encodes a homolog of vertebrate DRAL (down-regulated in
      rhabdomyosarcoma LIM-protein). This is the first clear example of a DRAL homolog
      in an invertebrate. Detectable developmental expression begins at the gastrula
      stage in the epidermis, but not in the neuroectoderm; thus the early stages of
      AmphiDRAL expression indicate the neural/non-neural boundary. During subsequent
      embryonic stages, expression continues in the epidermis (but not in the
      developing central nervous system) until it fades during the later larval stages.
      Copyright 1998 Elsevier Science Ireland Ltd. All Rights Reserved

PMID- 9767166
TI  - Immunohistochemical demonstration of serotonin-containing axons in the
      hypothalamus of the white-footed mouse, Peromyscus leucopus.
AB  - The wild white-footed mouse, Peromyscus leucopus, is commonly used for
      photoperiod studies utilizing physiological, behavioral, and other biological
      measures indicative of hypothalamic functions. Indoleamines, like melatonin and
      serotonin, are implicated in regulating these hypothalamic functions. Although
      neurochemical analyses of hypothalamic serotonin and its receptors have been
      reported for this species, the relevant neuroanatomy of the serotonin system
      within mouse hypothalamus has not been studied. A sensitive immunohistochemical
      method was used to detect serotonin within axons of coronal sections of
      formaldehyde fixed forebrain from P. leucopus. Large, medium and small diameter
      serotonin axons were evaluated in most regions, or nuclei, of the hypothalamus
      rostral to the mammillary region. A fourth type of serotonin axon was observed to
      have morphology characteristic of terminal arbors. The density of serotonin axons
      ranged from no staining to very high density similar to other species for which
      reports exist, i.e., rat, cat, and monkey. The ventromedial hypothalamic nucleus
      had distinctively lesser density of serotonin axons in this mouse than other
      species. Evidence of terminal arborization in hypothalamic nuclei and regions was
      evident. Neuroendocrine, autonomic, and behavioral functions of the hypothalamus
      are suggested to be regulated by input from serotonin terminals in this wild
      species of mouse, in correlation with receptor localization as reported by
      others.

PMID- 9767168
TI  - Involvement of the parafascicular nucleus in the facilitative effect of
      intracranial self-stimulation on active avoidance in rats.
AB  - To evaluate whether parafascicular nucleus (PF) is involved in the facilitative
      effect of lateral hypothalamic intracranial self-stimulation (LH-ICSS) on two-way
      active avoidance acquisition (5 sessions, 10 trials each, one daily) and long
      term retention (10 days), rats were lesioned bilaterally at the PF and implanted
      with an electrode aimed at the LH to obtain ICSS behavior. After each acquisition
      session rats were allowed to self-administer 2500 trains of LH-ICSS. The main
      results were: (1) LH-ICSS facilitated the acquisition and retention of
      conditioning; (2) PF lesions impaired both acquisition and retention of two-way
      active avoidance; (3) there was a positive relationship between PF lesions size
      and learning disruption, and (4) LH-ICSS failed to facilitate learning when PF
      was lesioned. We concluded that the lesion size is a critical variable to
      evaluate the effects of PF lesions on learning and memory, and that LH-ICSS
      treatment may exert their effects through the PF nucleus or, at least, the
      integrity of PF is required for LH-ICSS to improve clearly the task.

PMID- 9767169
TI  - Role of the cerebellum in exploration behavior.
AB  - Compared to +/+ mice, Lurcher (+/Lc) mutant mice whose cerebellar cortex is
      lacking almost all Purkinje cells and granule cells, exhibit a low level of
      exploration; this deficit is not due to a low level of activity but to both a
      decreased motivation to explore a novel environment and to spatial deficits. The
      characteristics of exploration in cerebellectomized +/+ and +/Lc mice suggest
      that the cerebellum is involved not only in cognitive but also in motivational
      processes.

PMID- 9767170
TI  - Renal sympathetic nerve activity in mice: comparison between mice and rats and
      between normal and endothelin-1 deficient mice.
AB  - Recently generated knockout mice with disrupted genes encoding endothelin (ET)-1
      showed an elevation of arterial blood pressure (AP) and supplied an evidence for
      intrinsic ET-1 as one of the physiological regulators of systemic AP. Little is
      yet known, however, why deficiency of ET-1, which was originally found as a
      potent vasoconstrictor, led to higher AP in these mice. To address this apparent
      paradox, we first developed a method to measure renal sympathetic nerve activity
      (RSNA) in mice using rats as reference and successively compared it between
      normal and ET-1 deficient mice. RSNA was successfully recorded in urethane
      anesthetized and artificially ventilated mice by a slight modification of the
      method used for rats. At basal condition, mean AP (MAP) and RSNA in ET-1
      deficient mice (105+/-2 mmHg and 9.71+/-1.49 muVs, n=20) were significantly
      higher than those in wild-type mice (96+/-2 mmHg and 5. 07+/-0.70 muVs, n=25).
      Basal heart rate (HR) and baroreflex-control of HR was not significantly
      different between the two. On the other hand, resting RSNA, RSNA range, and
      maximum RSNA were significantly greater in ET-1 deficient mice, and thus MAP-RSNA
      relationship was upwards reset. Hypoxia-induced increase in RSNA was not
      different between ET-1 deficient (73.4+/-9.4%) and wild-type mice (91.2+/-12.0%),
      while hypercapnia-induced one was significantly attenuated in ET-1 deficient mice
      (18.8+/-3.6 vs. 39.1+/-5.2% at 10% CO2). These results indicate that endogenous
      ET-1 participates in the central chemoreception of CO2 and reflex control of the
      RSNA. Baroreceptor resetting and normally preserved hypoxia-induced chemoreflex
      may explain a part of the elevation of AP in ET-1 deficient mice.

PMID- 9767171
TI  - Temporospatial characteristics of light-induced fos immunoreactivity in
      suprachiasmatic nuclei are not modified in Syrian hamsters treated neonatally
      with monosodium glutamate.
AB  - Neonatal treatment of rodents by intraperitoneal injections of monosodium
      glutamate (MSG) destroys many retinal ganglion cells whose neurons belong to the
      circadian system; howertheless, adults always synchronize their locomotor
      activity rhythm (LAR) to the light/dark cycle. Recent studies have shown that
      light-induced phase shifts of LAR are associated with the c-fos induction in
      suprachiasmatic nuclei (SCN) of nocturnal rodents. In this study, the circadian
      system was analyzed in treated and control hamsters maintained in constant
      darkness and exposed to light at circadian times (CTs) 13 and 18 during
      subjective night, 1 and 6 h after the onset of LAR. The period of the LAR and
      delay (CT13) and advance (CT18) phase shifts of LAR were not significantly
      different between MSG-treated and control hamsters. Temporospatial variations of
      Fos induction after light exposure were similar in both MSG-treated and control
      hamsters although the total number of Fos immunoreactive (Fos-ir) nuclei in the
      SCN was always lower in treated hamsters. However, the decrease in Fos-ir was
      significant only for the caudal third of the SCN of treated hamsters, the part
      where retinal afferents are most dense. The effect of light exposure on Fos
      expression in SCN of MSG-treated and control hamsters was the same at CT13 and
      CT18: (1) Fos-ir nuclei were significantly more numerous at CT18 than at CT13 in
      the rostral SCN; (2) dorsal Fos-ir cells were observed in the SCN only at CT18;
      (3) a ventral subgroup expressed Fos protein in intermediate SCN only at CT13.
      This study demonstrates that MSG-treatment does not significantly modify the
      phase-shifting effects of light on either the LAR or the associated cellular
      activation.

PMID- 9767172
TI  - Localization of glutathione and induction of glutathione synthesis-related
      proteins in mouse brain by low doses of gamma-rays.
AB  - First, we determined the cerebral localization of reduced glutathione (GSH) in
      normal mice by means of autoradiography using 99mTc-meso-hexamethyl propylene
      oxime. A highly specific localization of GSH in the cerebellum and hippocampus
      was observed. Secondly, we measured the elevation of GSH level in the brain after
      low-dose gamma-irradiation. The cerebral GSH levels increased soon after
      irradiation with 50 cGy of gamma-rays, reaching a maximum at 3 h post-treatment,
      then remaining significantly higher than that of the non-irradiated control until
      12 h and returning to the control level by 24 h. Thirdly, we examined the
      induction of the activities and the mRNAs of proteins involved in the synthesis
      and regeneration of GSH in the brain of mice subjected to low-dose gamma-ray
      irradiation. The level of mRNA for gamma-glutamylcysteine synthetase was
      significantly increased at 0.5 h, and remained high until 2 h post-irradiation
      (50 cGy). The level was transiently lowered to the non-irradiated control level
      at 3 h and slightly increased again after 6 h post-irradiation. gamma
      Glutamylcysteine synthetase activity was significantly increased 3 h after
      irradiation, and remained high up to 24 h post-irradiation. As for glutathione
      reductase, the mRNA level was increased at 0.5 h, and peaked strongly at 2 h,
      while the enzyme activity was significantly increased at 6 h after irradiation,
      and continued to increase up to 24 h. The level of mRNA for thioredoxin, which
      contributes to GSH biosynthesis by supplying cysteine to the de novo pathway,
      peaked between 0.5 h and 2 h post-irradiation, and rapidly declined thereafter.
      The content of thioredoxin showed a transient decrease immediately after
      irradiation, but was then remarkably elevated, reaching a maximum at 3 h, and
      thereafter declining sharply. These results indicate that the increase in
      endogenous GSH in mouse brain soon after low-dose gamma-ray irradiation is a
      consequence of the induction of GSH synthesis-related proteins and occurs via
      both the de novo synthesis and the regeneration pathways.

PMID- 9767173
TI  - Effects of brain endogenous insulin on neurofilament and MAPK in fetal rat neuron
      cell cultures.
AB  - We demonstrated the 'de novo' synthesis of insulin within the fetal nervous
      system in vivo and in vitro. We undertook this study to show a role for brain
      endogenous insulin within the fetal brain. We used neuron cell cultures (NCC)
      from 19 days gestational age fetal rat brains incubated in an insulin free/serum
      free defined medium. The neurons showed the presence of preproinsulin I and II
      mRNA using polymerase chain reaction and insulin immunoreaction employing
      peroxidase anti-peroxidase and radioimmunoassay techniques. Using an anti-pan
      neurofilament antibody (that recognizes non-phosphorylated neurofilaments)
      neurofilament immunoreaction (NFI) was observed within the neuron body, dendrites
      and axon. Either insulin antibody or isoproterenol treatment induced the neurites
      to retract and most of the neurons become round, with NFI confined to the neuron
      body. The antibody treatments induced the neurons to become hypertrophic and
      vacuolated. With PD98059 treatment NFI was only observed within the neuron body.
      The addition of insulin reversed the effects of isoproterenol and PD98059, but
      not those of the insulin antibody. Treatment with wortmannin had no effect.
      Western blot analysis showed that the basal level of mitogen activated protein
      kinase (MAPK) phosphorylation was inhibited by the treatment of the NCC with
      isoproterenol or trypsin, but was significantly increased by treatment with
      exogenous insulin, demonstrating that brain endogenous insulin phosphorylated
      MAPK (p<0.05). Thus, brain endogenous insulin promotes neurite outgrowth,
      probably via MAPK and by stimulating neurofilament distribution via this
      mechanism participates in neuron differentiation.

PMID- 9767175
TI  - Neurocalcin-immunopositive nerve terminals in the muscle spindle, Golgi tendon
      organ and motor endplate.
AB  - The present study revealed the immunohistochemical distribution of neurocalcin, a
      three EF-hand calcium-binding protein, in the rat muscles and tendons. In the
      muscle spindles, annulospiral endings, which made spirals around the intrafusal
      muscles, showed intense neurocalcin-immunoreactivity. In the Golgi tendon organs,
      immunopositive thick nerve fibers entered the collagenous fibers resulting in the
      projection of many swelling terminals. In all examined muscles, nerve terminals
      in the motor endplates showed neurocalcin-immunoreactivity associated with the
      membranes of synaptic vesicles and mitochondria. These findings suggest that
      neurocalcin is distributed and regulates calcium signaling in both afferent and
      efferent nerve terminals in the muscles and tendons.

PMID- 9767174
TI  - Spinal inputs from lateral columns to reticulospinal neurons in lampreys.
AB  - This study characterizes the inputs from the lateral columns of the spinal cord
      to reticulospinal neurons in the lampreys, using the in vitro isolated brainstem
      and spinal cord preparation. Synaptic responses to the electrical stimulation of
      the lateral columns were recorded in reticulospinal neurons of the posterior and
      middle rhombencephalic reticular nuclei. The responses consisted of a mixture of
      excitation and inhibition. They were markedly potentiated when using trains of
      two to five pulses, suggesting that the larger part of these synaptic responses
      was mediated via an oligosynaptic pathway. An early component, however, persisted
      when using twin pulses at 10-20 Hz on the ipsilateral side, suggesting the
      presence of an early mono- or disynaptic component. When increasing the
      stimulation strength, an early fast rising excitatory component appeared. It most
      likely resulted from an antidromic activation of vestibulospinal axons in the
      lateral tracts, which make en passant synaptic contacts with reticulospinal
      neurons. Responses were practically abolished by adding CNQX and AP5 to the
      Ringer's solution. The late component of excitatory responses was decreased by
      AP5, suggesting that NMDA receptors were activated. The NMDA receptor-mediated
      component was larger when using trains of stimuli or in Mg2+-free Ringer's. The
      application of NMDA depolarized reticulospinal neurons. The glycinergic
      inhibitory component was markedly increased in Mg2+-free Ringer's. Moreover,
      GABAB-receptor activation with (-)-baclofen abolished both excitatory and
      inhibitory responses. Taken together, the present results indicate that ascending
      lateral column axons generate large excitatory and inhibitory synaptic potentials
      in reticulospinal neurons. The possible role of these inputs in modulating the
      activity of reticulospinal neurons during locomotion is discussed.

PMID- 9767176
TI  - Sigmoidal compression rate-dependence of inert gas narcotic potency in rats:
      implication for lipid vs. protein theories of inert gas action in the central
      nervous system.
AB  - Inert gases at raised pressure exert anaesthetic effects. It is assumed that
      anaesthesia by the inert gases is fundamentally similar to anaesthesia produced
      by general anaesthetics. However, do general anaesthetics bind directly to
      proteins or influence activity by indirectly perturbing membrane lipids still
      remains a major question. Although the pressure required to achieve anaesthesia
      with inert gases has been suggested to exert potentially some pressure antagonism
      per se, this has not been studied yet to our knowledge. We investigated this
      possibility using nitrogen, argon, and nitrous oxide. Whatever the narcotic agent
      used, our results showed that the pressure of narcotic required to induce
      anaesthetic effects increased, as compression rate increased, in a sigmoid
      fashion rather than in a linear fashion. Evidence for sigmoidal responses vs.
      linear responses depended of the narcotic potency of the anaesthetic agent used
      (nitrogen: r2=0.973 vs. r2=0.941; argon: r2=0. 971 vs. r2=0.866; nitrous oxide:
      r2=0.995 vs. r2=0.879). Since a linear antagonism is predicted by lipid theories,
      we think it likely that these findings indicate that inert gases bind to a
      modulatory site of a protein receptor and act as allosteric modulators. Since
      other workers provided evidence for binding processes using volatile
      anaesthetics, the present findings could indicate that all classes of general
      anaesthetics, including inert gases, could act by binding directly to proteins
      rather than by dissolving in some lipids of the cellular membrane.

PMID- 9767177
TI  - Glucocorticoids interact with gp120 in causing neurotoxicity in striatal
      cultures.
AB  - A significant subset of HIV-positive patients suffer from AIDS-Related Dementia
      Complex (ADC), an array of neurologic and neuropsychologic impairments. The HIV
      coat protein gp120 has been implicated in the deleterious neurologic consequences
      of HIV infection, damaging neurons through a glutamatergic and calcium-dependent
      pathway. We have previously reported that glucocorticoids, the adrenal steroids
      secreted during stress, can exacerbate the neurotoxic and calcium-mobilizing
      effects of gp120 in hippocampal and cortical cultures. Because both the
      symptomatology of ADC, as well as the neuropathologic profile of post-mortem HIV
      brains suggests an involvement of the striatum, we examined whether
      glucocorticoids could also augment the damaging effects of gp120 in primary
      striatal cultures. We observe that neither gp120 nor the glucocorticoid
      corticosterone, when administered alone, cause neurotoxicity or mobilization of
      free cytosolic calcium; however, a combination of the two caused significant
      toxicity and neuron death. This, along with our prior findings of gp120
      glucocorticoid interactions, is striking, given the heavy clinical use of
      synthetic glucocorticoids for management of pulmonary complications of HIV
      infection.

PMID- 9767178
TI  - Diurnal rhythm in cyclic GMP/nitric oxide efflux in the medial preoptic area of
      male rats.
AB  - Since nitric oxide (NO) is implicated in the neuroendocrine control of
      luteinizing hormone-releasing hormone (LHRH) secretion and sexual behavior which
      show diurnal variations, we monitored cGMP levels (an index of NO activity) in
      the extracellular compartment of the medial preoptic area (MPOA) using
      microdialysis. It was observed that MPOA cGMP levels rose significantly in the
      afternoon in both castrated and intact male rats, thereby suggesting the
      existence of a diurnal rhythm in MPOA cGMP/NO efflux which may participate in
      eliciting the well-known diurnal variations in LHRH neuronal activity and male
      sexual behavior.

PMID- 9767179
TI  - Consecutive in vivo measurement of nitric oxide in transient forebrain ischemic
      rat under normothermia and hypothermia.
AB  - The effects of hypothermia on production of nitric oxide (NO) in ischemic brain
      were investigated by using in vivo microdialysis. Male Wistar rats were randomly
      divided into three groups; saline-treated normothermic group (37 degreesC, n=6),
      30 mg/kg N-nitro-l-arginine methyl ester(l-NAME)-treated normothermic group
      (n=6), and saline-treated hypothermic group (30 degreesC, n=6). Transient
      forebrain ischemia was produced by bilateral common carotid artery occlusion
      combined with hypotension (MABP=50 mmHg). Saline-treated normothermic animals
      resulted in a reduction of LCBF to 9% of baseline. Saline-treated hypothermic
      rats revealed the similar changes of LCBF. In contrast, l-NAME administration
      reduced the basal CBF to 85% of saline-treated group and to 8% after ischemia. NO
      products were decreased during ischemia and transiently increased after
      reperfusion in saline-treated groups. However, the increase of NO products after
      reperfusion was less significant in the hypothermia. l-NAME-treated group showed
      a constant reduction of NO production during ischemia and after reperfusion.

PMID- 9767180
TI  - Reduced glucose-induced neuronal activation in the hypothalamus of diet-induced
      obese rats.
AB  - Rats predisposed to develop diet-induced obesity (DIO) preferentially activate
      their sympathetic nervous system during intracarotid glucose infusion [B.E.
      Levin, Intracarotid glucose-induced norepinephrine response and the development
      of diet-induced obesity, Int. J. Obesity 16 (1992) 451-457.] but their brains are
      generally less responsive to glucose than diet-resistant rats (DR) [B.E. Levin,
      K.L. Brown, A.A. Dunn-Meynell, Differential effects of diet and obesity on high
      and low affinity sulfonylurea binding sites in the rat brain, Brain Res. 739
      (1996) 293-300.; B.E. Levin, B. Planas, Defective glucoregulation of brain alpha2
      adrenoceptors in obesity-prone rats, Am. J. Physiol. 264 (1993) R305-R311.; B.E.
      Levin, A.C. Sullivan, Glucose-induced norepinephrine levels and obesity
      resistance, Am. J. Physiol. 253 (1987) R475-R481.; B.E. Levin, A.C. Sullivan,
      Glucose-induced sympathetic activation in obesity-prone and resistant rats, Int.
      J. Obesity 13 (1989) 235-246.]. Here, 1 h intracarotid glucose infusions (4
      mg/kg/min) selectively increased Fos-like immunoreactivity (FLIR) in the
      hypothalamic paraventricular, ventromedial, dorsomedial and arcuate nuclei of
      inbred DR but not DIO rats. This suggests that enhanced glucose-induced
      sympathetic activation in DIO rats is related to a failure of glucose to produce
      neuronal activation in these areas.

PMID- 9767181
TI  - An increase in [3H] CGS21680 binding in the striatum of postmortem brains of
      chronic schizophrenics.
AB  - We measured adenosine 2a receptors in basal ganglia of 13 schizophrenics and 10
      controls, using [3H] CGS21680 as a ligand for the receptor binding assay. There
      was a significant increase in the specific [3H] CGS21680 binding in the putamen
      and caudate, but not in the globus pallidus of externa, of the schizophrenic
      patients, compared to those of controls. These results provide evidence
      suggesting that adenosine 2a receptors play a role in the pathophysiology of
      schizophrenia.

PMID- 9767182
TI  - Inducers of the cytochrome P-450 superfamily as promoters of carcinogenesis.
AB  - This review summarizes data on the mechanisms of tumor-promoting activity of non
      genotoxic compounds that are inducers of cytochrome P-450 isoforms. Their
      promoting activity is analyzed in term of synthesis of new cytochrome P-450
      isoforms. Active oxygen species formed by cytochrome P-450 isoforms can
      simultaneously act as stimulators of proliferation and inhibitors of
      intercellular communications. Promoter effects can be associated with changes in
      the ratio of cellular signaling non-protein molecules induced by newly
      synthesized cytochrome P-450 isoforms. Data on induction of cytochrome P-450
      isoforms of family 1 indicate that inducer interaction with its receptor causes
      cellular events resulting in the stimulation of cell proliferation.

PMID- 9767183
TI  - Extracellular proteolytic enzymes of filamentous fungi.
AB  - This review involves generalized data on extracellular proteases of filamentous
      fungi. General characteristics of secreted proteases and their classification are
      considered. Analysis of the data available revealed that fungi secrete only
      serine, aspartyl, and metalloproteases. Nothing is known about secretion of
      cysteine proteases; some available data do not have clear experimental evidence.
      Physicochemical and kinetic properties of the most typical extracellular
      proteases of different classes and families are discussed in detail. Special
      attention is focused in the review on regulation of synthesis of extracellular
      proteases and participation of the secreted proteases of pathogenic fungi in the
      infection process in animals, insects, or plants.

PMID- 9767184
TI  - Photoaffinity labeling of DNA polymerase from Thermus thermophilus and DNA
      template by photoreactive analogs of dCTP.
AB  - Substrate properties of dCTP analogs N4-[2-(4-azidotetrafluorobenzoylamino)
      ethyl]-2;-deoxycytidine-5; -triphosphate (FABdCTP), 5-[N-(4
      azidotetrafluorobenzoyl)-3-amino-trans-propen-1-yl] -2;-deoxycytidine-5;
      triphosphate (AlFABdCTP), and N4-[2-(2-nitro-5-azidobenzoylamino)-ethyl]-2;
      deoxycytidine-5; -triphosphate (NABdCTP) were studied in the reaction of DNA
      synthesis catalyzed by DNA polymerase from the extremely thermophilic bacterium
      Thermus thermophilus B 35 (Tte DNA polymerase). The enzyme was photoaffinity
      labeled with the mentioned derivatives, NABdCTP being used for the first time.
      The photoreactive primers containing FABdCTP and AlFABdCTP were synthesized in
      situ by Tte DNA polymerase and used in the complementary addressed labeling of
      DNA template. The efficiency of DNA template labeling is shown to be a function
      of the structure of the photoactive group.

PMID- 9767185
TI  - Human breast milk immunoglobulins G hydrolyze nucleotides.
AB  - Catalytically active antibodies, abzymes, appear in the blood of mammals
      immunized with the analogs of transition state or in the case of autoimmune
      diseases. Until recently, it was not shown whether abzymes exist in the blood of
      apparently healthy subjects. We have discovered that secretory IgA (sIgA) from
      the milk of healthy mothers catalyze phosphorylation of a variety of proteins and
      that IgG can hydrolyze DNA and RNA. In this study for the first time it is shown
      that IgG from human milk (and their Fab-fragments) also catalyze hydrolysis of
      nucleoside mono-, di-, and triphosphates. The data meet certain stringent
      criteria, unambiguously indicating that the observed catalytic activity is
      associated with IgG rather than contaminating enzymes. Although the nucleotide
      binding site of IgG is located in the light antibody chain, L-chains per se
      cannot hydrolyze NTP unlike the DNA-hydrolyzing abzymes. Kinetic and
      thermodynamic parameters that characterize the interaction of NTP and dNTP with
      IgG-abzymes were analyzed. Possible reasons for appearance of polyclonal abzymes
      with different catalytic activities in the milk of healthy mothers are
      considered.

PMID- 9767186
TI  - Interaction of human milk lactoferrin with ATP.
AB  - Human lactoferrin exhibits many unique properties. It is known as one of the most
      important factors that provide nonspecific defense of cells against bacteria,
      viruses, and carcinogenesis, as well as an important component of a specific
      system responsible for the passive immunity of newborns. As a compound with
      extremely broad spectrum of functions many of which were not elucidated so far,
      lactoferrin is intensely studied. In this study we obtained electrophoretically
      and immunologically homogenous preparations of lactoferrin from human milk. Using
      various methods, we were the first to show that the fraction of lactoferrin,
      which displays an increased affinity for Sepharose Blue, forms complexes with ATP
      with a stoichiometry of 1 mole ATP per mole protein. It is shown that the ATP
      binding site is located in the C-terminal domain of the lactoferrin molecule. The
      binding of ATP results in the dissociation of tetrameric forms of the protein and
      a change in the mode of interaction of lactoferrin with polysaccharides and other
      proteins. The data may be used in analysis of the possible reasons for
      multifunctional properties of lactoferrin and possible ways of regulation of its
      functions.

PMID- 9767187
TI  - Calorimetric studies of the thermal unfolding of smooth muscle myosin fragments
      and their complexes with ADP and phosphate analogs.
AB  - The thermal unfolding of turkey gizzard smooth muscle myosin subfragment 1 (S1)
      and heavy meromyosin (HMM) in the absence of added nucleotides, in the presence
      of ADP, and in S1 or HMM ternary complexes with ADP and Pi analogs, orthovanadate
      (Vi), beryllium fluoride (BeFx), or aluminum fluoride (AlF4-), have been studied
      by differential scanning calorimetry (DSC). It has been shown that the formation
      of these ternary complexes causes significant structural changes in S1 or in the
      heads of HMM which are reflected in a pronounced increase of the protein thermal
      stability. The effect of BeFx was less distinct than that of AlF4- or Vi.
      Phosphorylation of regulatory light chains (RLC) in S1 or in HMM had practically
      no influence on these effects. In general, the changes caused by various Pi
      analogs in smooth muscle S1 or HMM were similar to those observed earlier with
      skeletal muscle S1 devoid of RLC. It is concluded that RLC and their
      phosphorylation do not significantly affect the character of structural changes
      induced in motor domains of the HMM heads by the formation of ternary complexes
      HMM--ADP--Vi, HMM--ADP--AlF4-, and HMM--ADP--BeFx--stable analogs of the
      intermediate states of the HMM ATPase reaction, HMM.ADP.Pi and HMM. ATP.

PMID- 9767188
TI  - Structure of the decoding center of the ribosome.
AB  - The decoding center of the ribosome provides mRNA translation and the fidelity of
      the codon--anticodon interactions along with mRNA translocation in the course of
      protein biosynthesis. The three-dimensional structure of the ribosome decoding
      center is still unknown. However, up to now a number of direct and indirect
      experimental data on the structural and functional organization of the decoding
      center have been obtained. In this paper the main components of the decoding
      center are described on the basis of our own experimental results combined with
      data from the literature. A model of their spatial arrangement at the small
      ribosomal subunit is suggested.

PMID- 9767189
TI  - Radiation-induced lipoperoxidative stress in children coupled with deficit of
      essential antioxidants.
AB  - Catabolic products of the lipoperoxidative cascade (LPC), including diene
      conjugates, ketodienes, and carbonyl compounds, as well as essential lipid
      bioantioxidants (BAO)--vitamins E and A--were determined in blood plasma of 428
      children aged 0-7 years residents of areas contaminated with radionuclides after
      the Chernobyl Power Plant accident. Individual external gamma-irradiation doses
      (D) were determined. Gamma-irradiation accounted for more than 90% of total
      radiation loads and correlated with irradiation from absorbed sources in
      residents of the areas examined. Before examination, oral multivitamin therapy
      (with preparations containing the BAO determined in this work) was administered
      to a group of children (group I, n = 90) comparable to the group receiving no
      therapy (group II). Group II had two to six times higher mean levels of all LPC
      catabolic products and two to three times lower levels of vitamins E and A in
      comparison to age-matched subgroups of group I. In group II, individual shifts in
      the levels of all catabolic products achieved pathogenic stressor magnitudes at
      maximal regional radiation loads. Antenatal exposure and exposure over the first
      year of life caused the strongest pathogenic effects. BAO therapy strongly
      normalized the levels of LPC and vitamins (E and A) at all doses (up to 7 cSv)
      and increased the radiation resistance of the subjects. A total of 47 linear
      correlations were found at a p < 0.05 level (r = 0.4 to 0.7 for 54% and p < 0.02
      for 87% of equations) between low radiation doses and the extent of deviation of
      all metabolites studied from their normal levels. The multiplicity of radiation
      dose--effect correlations found under various conditions suggest that
      pathological signs found in the children examined were due to irradiation. LPC
      system disorders developed at low doses and displayed no threshold effect. The
      data suggest that these disorders resulted from free-radical chain-branched LPC
      reactions caused by chronic exposure to low doses of strongly ionizing radiation
      under conditions of BAO deficiency.

PMID- 9767190
TI  - Kinetic investigation of cooperativity in coenzyme binding by transketolase
      active sites.
AB  - The two-step mechanism of coenzyme (thiamine diphosphate, ThDP) binding with two
      initially identical active sites of apotransketolase has been examined with a
      kinetic model. Cooperativity between sites in the primary ThDP binding and in the
      following conformational transition has been analyzed. The only reliable
      difference between sites is shown to be the tenfold difference in the backward
      rate constants of the conformational transition; this means that the cooperative
      interaction between sites takes place only after termination of both steps of
      ThDP binding in both sites.

PMID- 9767192
TI  - Kinetics of all stages of electron transfer in nitrogenase in the presence of a
      photodonor.
AB  - A photodonor is considered as an alternative electron donor for nitrogenase. The
      kinetic mechanism of nitrogenase turnover is discussed. The turnover is initiated
      by the transfer of an electron to the enzyme and results in formation of a
      substrate molecule. The effective rate constant of concerted transfer of the
      first and the second electron from Av2 (Fe-protein) to Av1 (Mo-Fe-protein) and
      the rate constant of transfer of the second electron are 70 +/- 7 and 116 +/- 10
      sec-1, respectively. The rate constant of the rate-limiting reaction--MgADP
      release during formation of the superreduced state of Av1 (*Av12-)--is 12 +/- 2
      sec-1. Nitrogenase (E) states in complex E.N2 on binding and reduction of
      nitrogen are: E2, E4, E6 (2, 4, and 6 electrons).

PMID- 9767191
TI  - Xanthene dyes as photochemical donors for the nitrogenase reaction.
AB  - The ability of xanthene dyes to mediate photoinduced reduction of nitrogenase was
      tested. In addition to eosin, which was studied in the preceding work
      (Biochemistry (Moscow), 1996, 61, 2165-2172), 4', 5'-dibromofluorescein (DBF),
      cyanosine, and erythrosin are effective photodonors of an electron in the
      presence of NADH. Fluorescein, rhodamine B, rhodamine 6G, and porphyrins are
      unable to mediate photoinduced reduction of nitrogenase. The mechanism underlying
      different efficiency of xanthene dyes in this reaction was studied. At high
      concentrations, all xanthene dyes tested were shown to inhibit the intramolecular
      electron transfer in nitrogenase. The inhibiting concentration of DBF is 1.5.10-4
      M, whereas for other dyes, the inhibiting concentrations are less than 1.5.10-4
      M. Under otherwise identical conditions, the ATPase activity was inhibited by
      xanthene dyes to a lesser extent than the nitrogenase activity. DBF, the most
      effective photodonor, was also studied by differential kinetic pulse laser
      spectroscopy. Photoinduced reduction of nitrogenase, (Fe-proteinox.Mo-Fe
      protein).MgATP or (Av2ox.Av1).MgATP, was studied within the time range from 0 to
      100 msec. Two initial stages of the nitrogenase turnover were detected:
      photoinduced reduction of Av2 and electron transfer from Av2red to Av1. The
      kinetics of the photoinduced reduction of Av2.MgADP was studied in the presence
      of DBF (up to 1.3.10-4 M) both in solution and the complex with Av1. The apparent
      second-order rate constants of the photoinduced reduction of Av2.MgADP in
      solution and the complex with Av1 were determined as 9.7.107 +/- 106 and 1.2.108
      +/- 1.2.107 M-1. sec-1, respectively. The rate constant of the second reaction in
      the presence of another donor (dithionite) is 2500 times less. In complexes with
      Av1, the photochemical donor system DBF--NADH reduces Av2 more effectively than
      in free state in solution. In the presence of the photochemical donor system,
      neither photoreduction of Av2 in complexes with Av1 nor electron transfer from
      Av2red to Av1 are the rate-limiting stages of nitrogenase turnover.

PMID- 9767193
TI  - One year after CAPRIE, IST and ESPS 2. Any changes in concepts?
AB  - The IST, CAPRIE and ESPS-2 have shown that large collaborative randomised trials
      can be conducted in stroke medicine and can provide statistically and clinically
      significant results. They, and other concurrent studies, have highlighted the
      potential hazards of early anticoagulation, and the effectiveness and safety of
      early (and continuous) antiplatelet therapy in limiting early stroke recurrence
      and its consequences. In addition, they have shown that antiplatelet agents with
      differing mechanisms of action can have different effects, and perhaps additive
      effects when combined. The ESPRIT trial should delineate the roles of oral
      anticoagulant therapy, and the combination of aspirin and dipyridamole, in the
      prevention of stroke due to arterial disease. Future trials will hopefully
      determine the role in secondary stroke prevention of inhibitors of the platelet
      GPIIb/IIIa complex (the final common pathway of platelet aggregation), the
      combination of anitplatelet agents with different mechanisms of action (e.g.
      aspirin and clopidogrel, aspirin and IIb/IIIa inhibitors), the combination of
      antiplatelet agents and oral anticoagulants (which may simultaneously modify
      platelet function and fibrin production), and the combination of antithrombotic
      and cholesterol-lowering (statin) medications.

PMID- 9767194
TI  - Therapeutic inhibition of platelet function in stroke.
AB  - Platelet-dependent thrombotic- and thromboembolic-occlusive events are the usual
      cause of ischemic strokes. Antiplatelet strategies target one of the three
      platelet recruitment pathways (thromboxane A2, adenosine diphosphate, or
      thrombin) or the common cohesion pathway involving integrin alphaIIbbeta3
      fibrinogen receptors. Aspirin selectively and irreversibly interrupts TxA2 and
      decreases events by 20-25%. Clopidogrel selectively and irreversibly inactivates
      platelet-ADP receptors and reduces events by 30-35%. Additive effects are
      produced by combining aspirin and clopidogrel. Integrin alphaIIbbeta3 fibrinogen
      receptor antagonists, such as abciximab, produce dose-dependent inhibition of
      platelet recruitment and thrombo-occlusive events, regardless of the agonist(s)
      initiating platelet activation, but correspondingly impair platelet hemostatic
      function. Because chronic antiplatelet therapy has the potential for producing
      abnormal bleeding it is important for current clinical trials to evaluate the
      benefit risk relationship.

PMID- 9767195
TI  - Antithrombotic drugs: insights from cardiology.
AB  - The primary purpose of this overview is to provide an update on the newer
      antiplatelet drugs evaluated in clinical trials and introduced in clinical
      practice of modern cardiology. Despite the remarkable clinical developments with
      the use of new antiplatelet drugs, several fundamental issues remain unresolved.
      Some of the observed safety/efficacy problems in major clinical trials can be
      directly attributed to the lack of careful phase II studies where issues such as
      monitoring, pharmacological profiles, and individual response variations were not
      considered sufficiently. Nevertheless, none of the available antiplatelet agents
      meet all the criteria of an ideal antiplatelet agent. Aspirin has been the
      standard reference agent in cardiovascular disease. However, it is a weak and
      nonselective antiplatelet compound and is unable to interfere substantially with
      the thrombogenic activity of a fresh mural thrombus of a stenosed vessel. The
      newer antiplatelet drug classes such as the ADP receptor blockers (ticlopidine,
      clopidogrel) and the platelet glycoprotein IIb/IIIa receptor inhibitors produce
      their therapeutic effects by distinct mechanisms which differ from aspirin. Large
      clinical trials have documented their efficacy in acute coronary syndromes
      associated with intracoronary thrombus formation. The future challenge is to
      evaluate long-term treatment strategies which are equally safe but distinctly
      more effective than aspirin, e.g. a combination therapy with aspirin and
      clopidogrel or oral GP IIb/IIIa receptor antagonists.

PMID- 9767196
TI  - New genetic concepts and stroke prevention.
AB  - So far, stroke genetics has the reputation of daunting complexity and
      heterogeneity. However, progress through efforts at studying the human genome has
      provided novel technologies and focus, and 12 stroke genes or loci have already
      been identified in the last years, usually through the study of large pedigrees.
      However, particularly little is known about the ischemic form of stroke, and only
      recently could one chromosomal locus be shown to exert a major effect on stroke
      latency and outcome - through QTL studies in mouse strains. Whether the
      outstanding role of this one gene locus is also true in humans should be tested
      in linkage analyses of large pedigrees. The characterization of such families
      will probably be essential for progress in molecular genetics of ischemic stroke
      as well as being a challenge for clinical stroke centers.

PMID- 9767198
TI  - Introduction 

PMID- 9767197
TI  - New concepts for drug therapy after stroke. Can we enhance recovery?
AB  - Neurologic functions improve in most patients days and weeks after onset of a
      stroke. This can not be explained by recovery of the early salvageable ischemia
      zone. The most likely mechanism is relearning, a process in which healthy brain
      takes over functions lost with the infarct. Experimental studies indicate that
      this recovery can be modulated by pharmacological agents. NMDA antagonists and
      GABA agonists found to reduce infarct size in stroke models may have a harmful
      effect on relearning and neurologic recovery. This should be considered when
      clinical trial protocols are designed.

PMID- 9767199
TI  - Comparison of buprenorphine and methadone maintenance in opiate addicts.
AB  - As a maintenance agent for opioid dependency, buprenorphine offers advantages
      such as a lower level of dependence and minimal withdrawal symptoms, due to its
      partial agonist properties at the micro-opioid receptor. Previous studies have
      shown 8 mg sublingual buprenorphine to be equivalent to 60 mg oral methadone in
      terms of retention rate and opioid-negative urine levels. In a 24-week, ongoing
      European study, 34 opioid-dependent subjects were assessed; 16 receiving
      buprenorphine and 18 methadone. A free dosing schedule was used with no upper
      limit for methadone dosing but with a maximum buprenorphine dose of 8 mg.
      Screening prior to the study excluded subjects with polysubstance dependence,
      somatic disease and/or HIV infection. Primary outcome measures were abstinence
      from other drugs, for which subjects provided weekly urine samples for analysis
      of opioids, cocaine and benzodiazepines, and retention in treatment. Patients in
      the buprenorphine group provided a greater proportion of negative urine samples,
      in particular cocaine-negative samples, compared with the methadone group,
      although this was not statistically significant. Retention in the buprenorphine
      group was significantly lower than in the methadone group, suggesting that the 8
      mg buprenorphine limit may have biased the results in favour of methadone, and
      that this dose may have been too low for those subjects with high levels of
      dependence. However, buprenorphine is clearly effective in the more motivated
      subjects and further investigation in this subgroup is recommended.

PMID- 9767200
TI  - Substitution with buprenorphine in methadone- and morphine sulfate-dependent
      patients. Preliminary results.
AB  - In France, during the 1990s, there have been some rapid developments in the
      treatment of opioid addiction with the introduction of legal substitution agents.
      Originally, some patients were treated with morphine sulfate, but this was
      superseded by high dose buprenorphine (Subutex(R)) and methadone. This resulted
      in those patients originally treated with morphine being transferred to either of
      these two licensed products. A study investigating the effects of the transition
      from morphine to either buprenorphine or methadone was undertaken. Supplementary
      to this, a trial investigating transition between these new compounds was also
      conducted. The primary outcome measures for these trials were retention rate,
      which was assessed at 5, 9 and 12 months, and the precipitation of withdrawal
      symptoms. The studies showed that transferring patients between substitution
      agents can be accomplished without severe withdrawal symptoms, although specific
      management may be required for transfer from high doses of methadone to
      buprenorphine. High long-term retention rates were observed in the studies, with
      most drop-outs occurring directly after transfer. Results suggest that patients
      on long-term buprenorphine maintenance therapy may have good compliance in
      comparison with other agents.

PMID- 9767201
TI  - Comparison of buprenorphine and methadone in the treatment of opioid dependence.
      Swiss multicentre study.
AB  - A three-centre, randomised, double-blind study was designed to compare the
      efficacy and safety of buprenorphine and methadone. This was the first European
      study to compare these agents and was based on a previous trial performed in the
      US. Opioid-dependent subjects were randomised to receive either sublingual
      buprenorphine or oral methadone daily. Both objective and subjective measures of
      efficacy were monitored weekly, and safety parameters were regularly monitored
      over the entire six-week study. Urinalysis showed that the two treatments were
      similar with a slight increase in opioid-negative urines noted in both groups.
      The retention rate in the buprenorphine group was lower than in the methadone
      group, although it has been suggested that the buprenorphine dose may have been
      too low for some patients. None of the side effects noted were considered serious
      and all were attributable to chronic opioid dependence. Experience of two years
      substitution treatment in Fribourg suggests that initial induction onto
      buprenorphine allows for patients to be subgrouped before being given the most
      appropriate maintenance agent. Further investigation is required into the
      different dose-related effects of buprenorphine seen in particular subsets of
      addicts.

PMID- 9767202
TI  - The French experience--the pharmacist, general practitioner and patient
      perspective.
AB  - High-dose buprenorphine (Subutex(R)) has been available in France as a
      maintenance treatment since February 1996. Results from a twice yearly survey of
      pharmacists, general practitioners (GPs) and patients themselves in the use of
      Subutex(R) appeared to be representative of the general substitution therapy
      situation in France. Results from May 1997 were encouraging, with improved
      relationships between pharmacists and patients, and GPs and patients being
      reported in all three surveys. The most commonly prescribed dosage of
      buprenorphine (6-8 mg) was within the recommended range, although there was
      evidence that this was usually taken as several daily intakes by the majority of
      addicts. Although intravenous injection may occur in some cases, illicit resale
      was suspected only in a few cases. Treatment efficacy was high and retention at
      six months was good since patients had a positive opinion of their treatment and
      reported few adverse effects. Further improvement in the relationships between
      GPs and pharmacists is desirable to increase the success of the treatment
      programme.

PMID- 9767203
TI  - Differences between general practitioner- and addiction centre-prescribed
      buprenorphine substitution therapy in France. Preliminary results.
AB  - The treatment of heroin addiction in France relies on either general
      practitioners (GP) or specialist Addiction Centres (ACs). In general, the GPs
      offer a more flexible approach regarding frequency of consultations, urine tests
      and dosing regimen while the AC approach is more structured. A cohort study was
      undertaken to compare the treatment strategies of buprenorphine therapy between
      these medical environments. To determine the efficacy of each treatment, a number
      of outcomes were measured including the Addiction Severity Index, retention rates
      at 90 and 180 days, the average dose prescribed, quality of life assessment, body
      weight and two self-reported measures: treatment perception and predictive total
      duration. A total of 69 patients were enrolled; 32 treated by GPs and 37 treated
      in ACs. Significant differences, including average age, addiction severity and
      employment status were apparent between each group. Nevertheless, significant
      improvements in the social and medical status were observed in all patients after
      3 months, continuing after 6 months in both groups. Treatment retention was good
      in both groups with 65% of the total sample remaining after 180 days. The usually
      more flexible GP approach was more rigid in this study, resulting in an equally
      positive treatment outcome as seen in the ACs. The study highlights the
      effectiveness of buprenorphine in addicts with different social and medical
      backgrounds, regardless of the therapeutic approach.

PMID- 9767204
TI  - Preliminary assessment of a 10-day rapid detoxification programme using high
      dosage buprenorphine.
AB  - The original French therapeutic strategy for the treatment of opioid addiction
      was a rapid detoxification occasionally accompanied by treatment for withdrawal
      symptoms. In 1995, substitution therapy using opioids was introduced with the aim
      of maintenance, utilising methadone and the partial agonist buprenorphine,
      introduced in 1996. As well as being a maintenance agent, buprenorphine has been
      prescribed for rapid detoxification due to its reduced tendency to cause any
      withdrawal effects and its ability to block the effects of other opioids. This
      trial was initiated to measure the efficacy of buprenorphine in rapid
      detoxification and to assess whether additional medication would be required.
      Participants in this open study had requested rapid detoxification and were
      referred to the addiction clinic as inpatients. Patients were assessed by the
      clinician and during counselling sessions, and an initial dose was agreed upon.
      This dose was then gradually decreased over ten days in a flexible dosing
      schedule, with concurrent toxicological urinalysis to ensure no illicit drug use.
      During the trial, 25% of patients transferred to a maintenance programme and 58%
      remained in the study. The large transfer of patients to maintenance programmes
      may indicate that many people requesting rapid detoxification are actually asking
      for a more generalised form of assistance. No opioid-positive urines were noted
      after the fourth day in any patients, and the study indicates that buprenorphine
      should prove to be a useful detoxification agent, particularly in less hardened
      addicts. Step-down buprenorphine detoxification minimises withdrawal symptoms
      and, therefore, reduces the need for concurrent medication.

PMID- 9767205
TI  - Buprenorphine maintenance in pregnant opiate addicts.
AB  - Opioid maintenance agents such as methadone and slow-release morphine have
      provided beneficial effects in pregnant opioid-dependent women in both themselves
      and their child. However, one of the major drawbacks involved with these agents
      is that they cause an increase in the severity of neonatal abstinence syndrome
      (NAS) when compared to mothers using heroin. Consequently, a trial was performed
      to investigate the effects of buprenorphine use during pregnancy. A total of nine
      pregnant opioid-dependent women were transferred from either a mean daily dose of
      39.7 mg methadone or 400 mg slow-release morphine to a mean daily dose of 8.1 mg
      buprenorphine. The buprenorphine-maintained patients were integrated into an
      already established outpatient maintenance treatment programme covering all
      aspects of prenatal and perinatal care. Results demonstrated that buprenorphine
      administration in opioid-dependent pregnant patients is efficacious and well
      tolerated. Babies born to buprenorphine-maintained patients had birthweight and
      Apgar scores within the normal range (2,500-4,500 g and 9-10, respectively) and
      no evidence of opioid-related NAS was observed. The results from this preliminary
      study indicate the potential for buprenorphine maintenance therapy in pregnant
      addicts, although further research is required to confirm this hypothesis.

PMID- 9767217
TI  - Practices that minimize trauma to the genital tract in childbirth: a systematic
      review of the literature.
AB  - BACKGROUND: Trauma to the genital tract commonly occurs at birth, and can cause
      short- and long-term morbidity. Clinical measures to reduce its occurrence have
      not been fully identified. METHODS: A systematic review of the English language
      literature was conducted to describe the current state of knowledge on reduction
      of genital tract trauma before planning a large randomized controlled trial of
      ways to prevent such trauma. Randomized trials and other published reports were
      identified from relevant databases and hand searches. Studies were reviewed and
      assessed using a structured format. RESULTS: A total of 77 papers and chapters
      were identified and placed into 5 categories after critical review: 25 randomized
      trials, 4 meta-analyses, 4 prospective studies, 36 retrospective studies, and 8
      descriptions of practice from textbooks. The available evidence is conclusive in
      favor of restricted use of episiotomy. The contribution of maternal
      characteristics and attitudes to intact perineum has not been investigated.
      Several other topics warrant further study, including maternal position, style of
      pushing, and antenatal perineal massage. Strong opinions and sparse data exist
      regarding the role of hand maneuvers by the birth attendant for perineal
      management and birth of the baby. This became the topic of the planned randomized
      controlled trial, which was completed; results will be published soon.
      CONCLUSIONS: The case for restricting the use of episiotomy is conclusive.
      Several other clinical factors warrant investigation, including the role of hand
      maneuvers by the birth attendant in preventing birth trauma. A large randomized
      controlled trial will report on this topic.

PMID- 9767218
TI  - Postpartum early hospital discharge and follow-up practices in Canada and the
      United States.
AB  - BACKGROUND: Although official guidelines and recent legislation have addressed
      early postpartum hospital discharge and follow-up, little is known about the
      practices of obstetricians in Canada and the United States on this issue.
      METHODS: Questionnaires were mailed to two separate random samples of 2000
      Fellows of the American College of Obstetricians and Gynecologists (ACOG) in the
      United States and all Canadian Fellows. Practices and perceptions were compared
      with those recommended in the literature, recent legislation, and guidelines of
      ACOG and American Academy of Pediatrics (AAP). RESULTS: In contrast to concerns
      expressed in the medical literature and official AAP/ACOG guidelines, many
      physicians considered potential psychosocial and demographic risk factors
      relatively unimportant in making early discharge decisions, preferring to
      emphasize aspects of the patient's medical condition, hospital course, and social
      support. Although the official guidelines encourage follow-up for all patients
      discharged early, additional visits are routinely advised by only 39 percent of
      obstetricians after vaginal delivery and by 68 percent after cesarean section.
      After vaginal delivery 39 percent of obstetricians used telephone follow-up and
      37 percent after cesarean delivery. Moreover, although the official guidelines
      recommend follow-up within 48 hours of discharge, only one-half of the
      obstetricians surveyed advised follow-up at this time. In contrast to the
      guidelines, most obstetricians defined early discharge as that occurring within
      24 hours after vaginal delivery and 72 hours after cesarean delivery; most
      defined optimal lengths of stay within the 48-hour (after vaginal delivery) and
      96-hour (after cesarean delivery) periods considered short by the guidelines.
      CONCLUSIONS: Current postpartum early discharge and follow-up practices emphasize
      the physical health of the mother and place little emphasis on social risk. They
      appear to be influenced by perceptions of the appropriateness of the length of
      stay and are not in agreement with professional guidelines.

PMID- 9767219
TI  - Intention to breastfeed in low-income pregnant women: the role of social support
      and previous experience.
AB  - BACKGROUND: The purpose of this study was to describe the relationship between
      breastfeeding intention among socioeconomically disadvantaged pregnant women and
      maternal demographics, previous breastfeeding experience, and social support.
      METHODS: A cross-sectional, convenience sampling strategy was employed for data
      collection. Low-income women (n = 1001) in a public hospital completed a six-page
      questionnaire about their infant feeding plans, demographics, and social support.
      Simple regression analyses were conducted to compare maternal breastfeeding
      intention with the hypothesized correlates. RESULTS: Breastfeeding intention was
      positively correlated with older maternal age, higher education, more
      breastfeeding experience, Hispanic ethnicity, and hearing about breastfeeding
      benefits from family members, the baby's father, and lactation consultants, but
      not from other health professionals. Health professionals' attitudes were less
      influential on women's infant feeding decisions than the attitudes and beliefs of
      members of women's social support networks. When controlling for breastfeeding
      experience (none vs any), some findings, varied, indicating a need for
      breastfeeding interventions tailored to women's level of experience. CONCLUSION:
      Use of peer counselors and lactation consultants, inclusion of a woman's family
      members in breastfeeding educational contacts, and creation of breastfeeding
      classes tailored to influential members of women's social support networks may
      improve breastfeeding rates among low-income women, especially those with no
      breastfeeding experience, more effectively than breastfeeding education to
      pregnant women that is solely conducted by health professionals.

PMID- 9767220
TI  - What contributes to breastfeeding success after childbirth in a maternity ward in
      Finland?
AB  - BACKGROUND: The study objective was to gain information about factors that
      contribute to the successful establishment of breastfeeding in first-time mothers
      while they are still in the maternity hospital. The study was part of a wider
      longitudinal project that examined the development of first-time mothers into
      motherhood during eight months after the birth. METHODS: Data were collected by a
      questionnaire distributed between January and May 1995. The sample comprised 326
      first-time mothers, who completed the questionnaires on about the fifth day after
      childbirth. A polychotomic logistic regression analysis was applied. RESULTS:
      Mothers who had a positive experience of breastfeeding in the maternity ward and
      who began lactating 2 to 3 days postpartum coped better with breastfeeding than
      those whose experience was less positive and who lactated later. Moreover, the
      greater the emotional (affect) and concrete (aid) support received by the mother
      from members of her support network, the better she coped with breastfeeding. By
      contrast, those mothers who were upset while in the maternity ward coped less
      well with breastfeeding. CONCLUSIONS: Establishing successful breastfeeding in
      first-time mothers requires the professional guidance and support of the
      maternity staff and paying attention to the person closest to the new mother, who
      in this study was the spouse or father of the child.

PMID- 9767221
TI  - Maternal perceptions of labor with fetal monitoring by pulse oximetry in a
      research setting.
AB  - OBJECTIVE: Little research has evaluated maternal experience with fetal pulse
      oximetry for fetal surveillance. The purpose of this study was to compare
      maternal perceptions of labor with intrapartal cardiotocography with or without
      fetal pulse oximetry in a research setting. METHODS: One hundred women with
      vaginal, vertex deliveries and uncomplicated fetal outcomes were enrolled. The
      study group was a subset of 50 mothers who had participated in a pulse oximetry
      trial. The control group of 50 mothers was monitored by cardiotocography only.
      Both groups were matched for age, parity, weeks of gestation, epidural anesthesia
      use, and duration of labor. A global measure of maternal perception of labor was
      established by experience with labor, general attitude toward monitoring devices,
      satisfaction with monitoring, nursing and medical care, and anxiety, each of
      which was evaluated separately. The mothers in the study group were also
      interviewed about aspects related to the fetal pulse oximetry research setting,
      such as information, movement restriction, discomfort, care, privacy, and safety.
      The questionnaires were based on a standardized rating scale model, and the
      interviews were conducted two to four days after delivery. The results were
      analyzed by chi-squared, paired t test, and ANOVA. RESULTS: No significant
      differences were observed between the study and control participants in any
      parameter concerning the maternal perception of labor. Mothers' experiences with
      pulse oximetry as assessed by interview was overwhelmingly positive. CONCLUSIONS:
      Fetal monitoring by pulse oximetry in a research setting did not affect maternal
      perceptions of labor. Mothers' experiences with pulse oximetry were highly
      positive, suggesting that research in fetal pulse oximetry need not compromise
      maternal perceptions of labor.

PMID- 9767222
TI  - Maternity care in The Netherlands: the changing home birth rate.
AB  - In 1965 two-thirds of all births in The Netherlands occurred at home. In the next
      25 years, that situation became reversed with more than two-thirds of births
      occurring in hospital and fewer than one-third at home. Several factors have
      influenced that change, including the introduction of short-stay hospital birth,
      hospital facilities for independent midwives, increased referral rates from
      primary to secondary care, changes in the share of the different professionals
      involved in maternity care, medical technology, and demographic changes. After a
      decline up to 1978 and a period of relative stability between 1978 and 1988, the
      home birth rate started to decline further, to the extent that it might
      destabilize the Dutch maternity care system and the role of midwives in it. The
      Dutch maternity care system depends heavily on primary caregivers, midwives and
      general practitioners who are responsible for the care of women with low-risk
      pregnancies, and on obstetricians who provide care for high-risk pregnancies. Its
      preservation requires a high level of cooperation among the different caregivers,
      and a functional selection system to ensure that all women receive the type of
      care that is best suited to their needs. Preserving the home birth option in the
      Dutch maternity care system necessitates the maintenance of high training and
      postgraduate standards for midwives, the continued provision of maternity home
      care assistants, and giving women with uncomplicated pregnancies enough
      confidence in themselves and the system to feel safe in choosing a home birth.

PMID- 9767223
TI  - Ethnic differences in birth outcomes: the search for answers continues.

PMID- 9767224
TI  - Sheila Kitzinger's letter from Europe: court-ordered cesareans in the United
      Kingdom.

PMID- 9767227
TI  - Editor's choice 

PMID- 9767228
TI  - Port-wine stains unresponsive to pulsed dye laser: explanations and solutions.
AB  - The flashlamp-pumped pulsed tunable dye laser has represented a significant
      advance in the treatment of port-wine stains (PWS). However, not all patients
      will respond. In this review, the clinical features influencing the response of
      PWS to the pulsed dye laser will be discussed. Theoretical and clinical data are
      presented to explain why not all PWS will respond to this laser. Methods to
      overcome the problems of non-responding PWS are suggested, including new
      treatment devices and techniques.

PMID- 9767226
TI  - Cesarean delivery rates in Chile.

PMID- 9767229
TI  - Immunohistochemical demonstration of carcinoembryonic antigen and related
      antigens in various cutaneous keratinous neoplasms and verruca vulgaris.
AB  - Carcinoembryonic antigen (CEA), which is a well-known marker for the normal sweat
      gland apparatus and its neoplasms in the skin, was recently demonstrated in
      sebaceous neoplasms. The aim of this study was to examine the expression of CEA
      and related antigens in the other cutaneous keratinous neoplasms and verruca
      vulgaris. Normal adult skin, squamous cell carcinoma (SCC), senile keratosis,
      Bowen's disease, basal cell carcinoma (BCC), seborrhoeic keratosis and verruca
      vulgaris were stained immunohistochemically with a panel of monoclonal and
      polyclonal antibodies that recognize different epitopes of CEA and related
      molecules. Localization of the antigens was compared with that of involucrin and
      proliferating cell nuclear antigen. The strongest expression of CEA-related
      antigens, other than non-specific cross-reacting antigen (NCA) -50/90, was seen
      in SCC and verruca vulgaris, while no detectable expression was seen in BCC.
      Senile keratosis, Bowen's disease and seborrhoeic keratosis showed the
      predominance of the CEA-related antigens over CEA weakly expressed. Strong
      expression of both CEA and NCA-50/90 was seen only in SCC. All the expressions
      were limited to the cells situated in the upper epidermal cell layers of the
      tumours, at the centre of tumour islands in SCC and along the pseudohorn cysts in
      seborrhoeic keratosis, where involucrin was coexpressed. We suggest that CEA and
      related antigens are not only markers for sweat gland differentiation in the
      skin, as currently accepted, but are also expressed in various cutaneous
      keratinous neoplasms and verruca vulgaris. The expression may correlate with the
      terminal differentiation of the tumour cells, the strong coexpression of CEA and
      NCA-50/90 may correlate with the malignant potential of the tumour types, and the
      mechanisms that control the expression of CEA and related antigens in the
      neoplasms may be similar to those operative in verruca vulgaris.

PMID- 9767230
TI  - Fas ligand is expressed in normal skin and in some cutaneous malignancies.
AB  - Fas, a cell surface receptor and member of the tumour necrosis factor receptor
      superfamily, induces apoptosis upon oligomerization by its ligand (Fas ligand:
      FasL). Detailed studies have revealed that Fas is broadly expressed in normal
      human tissues, but relatively little is known about the range of cell types
      capable of expressing FasL. The aim of this study was to determine the in vivo
      patterns of expression of Fas and FasL in human skin tissues.
      Immunohistochemistry was performed using paraffin-embedded samples of normal and
      neoplastic skin tissues. In normal skin, FasL was expressed in the epidermis,
      sebaceous glands, sweat glands and outer root sheath of the hair. In squamous
      cell carcinomas (SCC), all cases analysed expressed FasL at high levels, whereas
      60% of basal cell carcinomas (BCC) were positive for FasL. Expression of Fas in
      normal skin was observed in the basal and spinous layers of the epidermis, the
      outer root sheath of the hair, and the sebaceous glands. Expression of Fas was
      observed in all the SCC tested and none of the BCC tested. Expression of FasL by
      normal cells and tumour cells in skin tissue, demonstrated for the first time in
      the present study, may provide an important clue to understanding skin
      physiology, and immune evasion of skin tumours.

PMID- 9767231
TI  - Expression of fibrogenic cytokines in desmoplastic malignant melanoma.
AB  - Desmoplastic malignant melanoma (DMM) consists of amelanotic spindle-shaped
      melanoma cells and is accompanied by desmoplasia with fibrous stromata. It has a
      strong tendency for local infiltrative growth and recurrence and a propensity for
      neurotropism. It is not yet known which cytokine is responsible for the
      desmoplasia in DMM. In the present study, we investigated the roles of several
      fibrogenic cytokines and cytokine receptors in DMM: basic fibroblast growth
      factor (bFGF), connective tissue growth factor (CTGF), transforming growth factor
      beta, platelet-derived growth factor (PDGF) and PDGF receptors. Immunostaining
      and in situ hybridization were conducted in four cases of DMM and four cases of
      amelanotic malignant melanoma (AMM) as negative controls for desmoplasia. PDGF
      beta receptor, bFGF and CTGF were intensely expressed in the DMM specimens in
      comparison with the AMM specimens. The reaction of PDGF-B ligand and CTGF to PDGF
      beta receptor, in addition to the expression of bFGF, may contribute to the
      desmoplasia in DMM.

PMID- 9767232
TI  - Expression of CD95 ligand in melanocytic lesions as a diagnostic marker.
AB  - CD95 ligand (CD95L) potently induces apoptosis by activating CD95 on target
      cells. It has recently been reported that melanoma cells in vivo express a
      significant amount of CD95L, thereby being immediately able to kill CD95-bearing
      immunocompetent cells specific for cancer antigens, which infiltrate the lesions.
      In this study, we employed immunohistochemistry using an antibody directed
      against CD95L to investigate at which stage the melanoma CD95L expression is
      turned on. Skin biopsies of 49 lesions from 46 patients were assessed. These
      included benign and dysplastic naevi, melanoma in situ, stage I melanomas
      (Clark's level 2 or 3), advance-phase melanomas (Clark's level 4 or 5) and lymph
      node metastases. CD95L was expressed in all of the advance-phase melanomas as
      well as lymph node metastases of cutaneous origin, whereas neither melanoma in
      situ, benign naevi nor dysplastic naevi reacted positively with the antibody. To
      investigate a link between positivity and tumour size, the data were analysed on
      the basis of Breslow thickness, and indicated that expression was observed only
      when tumours were thicker than 0.75 mm. We next compared expression of CD95L and
      HMB-45. CD95L was positive only in melanomas in a more advanced phase than stage
      I, whereas HMB-45 was not only expressed in melanoma cells but also in benign
      pigmented naevi. This indicated the advantage of CD95L staining to diagnose
      melanoma. The present study indicates the significant correlation between
      tumorigenicity and expression of CD95L, and thereby raises the possibility that
      CD95L may be a useful diagnostic marker for malignant melanomas.

PMID- 9767233
TI  - Functional regulation of tyrosinase and LAMP gene family of melanogenesis and
      cell death in immortal murine melanocytes after repeated exposure to ultraviolet
      B.
AB  - This study characterizes the induction of melanogenesis and the expression of
      tyrosinase, tyrosinase-related protein (TRP) and lysosome-associated membrane
      protein (LAMP) gene families in the cultured melanocyte lines of non-agouti mice
      with four major genetic loci, i.e. melan-a2 (black, wild type), melan-b (brown,
      TRP-1 mutation), melan-s (black, piebaldism mutation) and melan-c (white,
      tyrosinase mutation) in response to repeated exposure to ultraviolet (UV) B (5
      mJ/cm2, 7 consecutive days). Electron microscopy showed that new melanogenesis
      was induced in melan-a2, melan-s and melan-b melanocytes. Melan-a2, melan-s and
      melan-b showed an almost twofold increase in tyrosinase activity and gene
      expression with increased synthesis of melanosomes, although melan-b showed a
      minimum increase in tyrosinase activity. There was a twofold upregulation of LAMP
      1 mRNA but no alteration in LAMP-2 and LAMP-3 mRNA expression in melan-a2, while
      there was no alteration in LAMP-1 mRNA expression but increased expression of
      LAMP-2 and LAMP-3 mRNA in melan-s, LAMP-3 showing a higher increase. Melan-b
      cells showed the same gene expression of LAMP-1, LAMP-2 and LAMP-3 as that of non
      UV exposed cells. All three lines, however, exhibited simultaneously cell death,
      melan-b reaching the highest rate of cell death (96.5%). In contrast, melan-c,
      which did not have any tyrosinase activity with failure of melanogenesis
      induction, expressed all the mRNAs of the tyrosinase and LAMP gene families, but
      was not associated with any significant melanocyte death. Our study indicated:
      (i) that melanogenesis induction and melanocyte death are two photobiological
      processes occurring simultaneously after repeated UVB exposure, (ii) that in
      response to an upregulation of tyrosinase mRNA and enzymic activity, there was a
      co-ordinated upregulation of the LAMP-1 gene in wild type melan-a2, while no
      upregulation was found in melan-s and melan-b mutants, and (iii) that UV-induced
      melanocyte death is related to the upregulation of the tyrosinase gene, induction
      of new melanogenesis and mutation of the TRP-1 gene in immortal murine
      melanocytes.

PMID- 9767234
TI  - Modulation of melanocyte-stimulating hormone receptor expression on normal human
      melanocytes: evidence for a regulatory role of ultraviolet B, interleukin-1alpha,
      interleukin-1beta, endothelin-1 and tumour necrosis factor-alpha.
AB  - Melanocyte-stimulating hormone (MSH) receptor binding activity and melanocortin-1
      receptor (MC1-R) gene expression on normal human melanocytes have been studied as
      responses to the effects of ultraviolet B (UVB), interleukin-1 (IL-1), endothelin
      1 (ET-1) and tumour necrosis factor-alpha (TNF-alpha), which are known as UV
      sensitive regulators of melanocytic function. MSH receptor (MSH-R) binding
      activity was upregulated by UVB, IL-1alpha, -1beta and ET-1, but was
      downregulated by TNF-alpha. Northern blot analysis showed that MC1-R mRNA
      expression was induced 24 h after UVB irradiation in a dose-dependent manner, and
      that 24-h treatment with ET-1 also induced an expression of MC1-R mRNA, whereas
      TNF-alpha downregulated the expression. In addition, IL-1alpha and -1beta have a
      small but real inductive effect on MC1-R mRNA expression. Taken together, our
      results suggest a model in which higher MC1-R mRNA expression is accompanied by
      upregulation of MSH-R binding activity, and enhanced by UVB or cytokines
      sensitive to UVB. Such a regulatory system would enable normal human melanocytes
      to respond to MSH more efficiently and induce an increase of melanization of the
      skin through the MSH/MSH-R system after UVB radiation.

PMID- 9767235
TI  - Ultraviolet B induced suppression of induction of contact sensitivity in human
      skin is not associated with tumour necrosis factor-alpha-308 or interleukin-10
      genetic polymorphisms.
AB  - Low doses of ultraviolet B (UVB) can induce localized immunosuppression in skin.
      This effect may be important in the induction of skin cancers and is thought to
      be mediated by tumour necrosis factor (TNF) alpha and interleukin (IL) 10 in
      conjunction with other factors. In humans a transition polymorphism in the TNF
      alpha gene may affect TNF-alpha secretion and the promoter region of the IL-10
      gene contains a CA repeat polymorphism which may affect gene function. We have
      therefore investigated the association of these polymorphisms with UVB-induced
      immunosuppression in humans. Volunteers (n = 42) were irradiated with UVB then
      sensitized on irradiated skin with diphenylcyclopropanone (DPCP) and subsequently
      antigen challenged with DPCP. DNA was extracted from blood samples and volunteers
      genotyped for the TNF-alpha polymorphism by polymerase chain reaction (PCR) and
      restriction digestion. The CA repeat polymorphism was amplified by PCR and sized
      by gel electrophoresis. Twenty-four volunteers were susceptible to UVB-induced
      immunosuppression and 18 were resistant. The association of allele frequencies
      and phenotype was statistically tested using a chi2-test. For both the TNF-alpha
      and IL-10 polymorphisms, there was no statistically significant association
      between allele types and response to UVB. These results indicate that variation
      in the immune response to UVB in humans is not associated with the TNF-alpha-308
      transition or IL-10 CA repeat polymorphisms, although other as yet undetected DNA
      sequence variants of these genes may be involved.

PMID- 9767237
TI  - Effect of granulocyte macrophage-colony stimulating factor on Langerhans cells in
      normal and healthy atopic subjects.
AB  - Granulocyte macrophage-colony stimulating factor (GM-CSF) is a multipotent
      cytokine produced by many cutaneous cell types including keratinocytes.
      Langerhans cells (LC) represent the major antigen-presenting cells in skin, and
      in vitro studies demonstrate that GM-CSF is of pivotal importance in LC. Healthy
      volunteers (n = 3 non-atopic, n = 3 with atopy) received recombinant human GM-CSF
      (0. 05 microg/mL) by intradermal injection for 3 days to the same site. Diluent
      was injected in a similar manner as control. Biopsies were taken 24 h after the
      final injection and examined immunohistochemically for LC and inflammatory cell
      markers. Compared with control sites, intradermal GM-CSF resulted in shortening
      of dendritic cell processes and redistribution of LC in the epidermis; numbers of
      CD1a + cells in the epidermis were significantly decreased (P < 0.005), while
      those in the dermis were significantly increased (P < 0.05) following intradermal
      GM-CSF when compared with controls. Double labelling studies on epidermal CD1a +
      cells indicated de novo expression of intercellular adhesion molecule (ICAM)-1
      and increased expression of HLA-DR following GM-CSF (P < 0. 005, P < 0.005,
      respectively). Additional findings included a marked mixed inflammatory cell
      infiltrate in the dermis and increased expression of the endothelial cell
      adhesion molecules E-selectin and ICAM-1. These data indicate that in normal
      human skin, GM-CSF induces changes in the phenotype and distribution of CD1a +
      cells consistent with LC functional maturation and exit from the epidermis to the
      dermis. As these events are central to the initiation of cutaneous inflammation,
      GM-CSF may potentially play a critical role in the pathogenesis of inflammatory
      dermatoses.

PMID- 9767236
TI  - Comparative immunotoxicology of ultraviolet B exposure I. Effects of in vitro and
      in situ ultraviolet B exposure on the functional activity and morphology of
      Langerhans cells in the skin of different species.
AB  - Ultraviolet (UV) B-induced morphological and functional changes in the skin of
      mice, rats and humans were investigated. Changes in the morphological structure
      of Langerhans cells (LC), the major antigen-presenting cells in the skin, using
      confocal laser scanning microscopy, were found in mouse and rat skin after in
      situ exposure to high doses of UVB radiation (FS40) (3-9 kJ/m2). Similar UVB
      doses failed to induce alterations in the morphological structure of human LC.
      Alterations in the function of epidermal cells (especially LC) were studied,
      using the mixed skin lymphocyte response (MSLR). In vitro UVB exposure of
      epidermal cells (EC), derived from the skin of the different species, revealed
      that low doses of UVB radiation impaired the stimulatory capacity of these cells
      dose-dependently; mouse epidermal cells were most UVB-susceptible, while human
      cells were least UVB susceptible. For suppression of the stimulatory capacity of
      EC after in situ UVB exposure of skin tissue, higher doses of UVB radiation than
      the in vitro UVB exposure were needed in all species tested. Also in this in situ
      set-up mouse epidermal cells were most UVB-susceptible, and human epidermal cells
      were least UVB-susceptible. The magnitude of differences in susceptibility for
      UVB-induced changes in the stimulatory capacity of EC after in situ and after in
      vitro exposure experiments was similar. Firstly, it may be concluded that UVB
      impairs the functional activity of LC at a lower dose than that which alters the
      morphology of these cells. Secondly, it is clear that epidermal cells, especially
      LC, from the skin of rodents are more susceptible to UVB than epidermal cells
      derived from human skin. It is important to account for these differences in
      susceptibility when data on the effects of UVB radiation on the immune system in
      rodents are extrapolated to humans.

PMID- 9767238
TI  - Expression of the small heat shock protein HSP 27 in developing human skin.
AB  - The 27 kDa heat shock protein (HSP 27) is expressed in keratinocytes of the upper
      epidermal layers, and recent evidence suggests that this protein is involved in
      the regulation of epidermal differentiation. The expression of HSP 27 was
      investigated in developing human skin by immunohistochemistry utilizing a
      specific monoclonal antibody. We used formalin-fixed, paraffin-embedded tissue of
      abdominal skin obtained from 34 human fetuses ranging between 13 and 30 weeks
      estimated gestational age (EGA). We found that HSP 27 is not expressed in
      keratinocytes until week 14 EGA. At this stage staining is observed in the
      periderm and the upper intermediate cells but not in hair germs. During further
      development, HSP 27 expression correlates with increasing epidermal
      differentiation, i.e. shedding of the periderm and beginning of keratinization.
      HSP 27 expression is confined to the upper cell layers and sparse basal cells. In
      hair follicles, HSP 27 can be detected in the innermost cell layer of the outer
      root sheath and in keratinocytes of the bulge identical to what is observed in
      adult skin. The hair papilla, matrix cells and sebaceous glands are negative for
      HSP 27 and remain so during further development. In eccrine sweat glands of the
      24th week EGA, HSP 27 is confined to the superficial cell layer of the sweat
      ducts. In the present report we demonstrate differentiation-related expression of
      HSP 27 in developing human skin. Further in vitro studies will address the
      molecular function of HSP 27 in epidermal differentiation and development.

PMID- 9767239
TI  - Seborrhoeic dermatitis is not caused by an altered immune response to Malassezia
      yeast.
AB  - The immune response of patients with seborrhoeic dermatitis and healthy age- and
      sex-matched controls was examined to test the hypothesis that an inadequate or
      inappropriate immune response to Malassezia yeast leads to seborrhoeic
      dermatitis. Antibody responses were examined using enzyme-linked immunosorbent
      assays (ELISAs) and Western blots and lymphocyte responses using lymphocyte
      proliferation assays. The level of IgG and IgM specific for whole yeast cells or
      extracted proteins of two isolates of M. furfur was tested in ELISA. A wide range
      of antibody levels was found but the patient and control groups were
      indistinguishable (n = 19), and the groups could not be distinguished by the
      pattern of Malassezia proteins recognized by their sera in Western blots. The
      average affinity of the subjects' antibodies specific for Malassezia cells or
      proteins was measured using ammonium thiocyanate dissociation. Most of the sera
      had moderate affinities corresponding to 50% dissociation at thiocyanate
      concentrations of 0.5-1.0 mol/L. There was no difference between patients and
      matched controls. The proliferation of the patients' lymphocytes in response to a
      number of M. furfur cell preparations was measured: whole cells, cytoplasmic
      proteins, cell walls, soluble molecules extracted from the cell walls using
      sonication, and a commercial preparation. There was a wide range of responses
      between individuals, but there was no difference between the three groups:
      patients with seborrhoeic dermatitis (n = 16), healthy controls (n = 16) and a
      group suffering from other inflammatory skin conditions (n = 15). The results do
      not support the hypothesis that an inadequate immune response to Malassezia yeast
      could lead to seborrhoeic dermatitis. Other possible pathological mechanisms
      include toxin production or lipase activity.

PMID- 9767240
TI  - Allergens in combination have a synergistic effect on the elicitation response: a
      study of fragrance-sensitized individuals.
AB  - Perfume ingredients were chosen as model substances to study the effect of
      allergens in combination on the elicitation response. Two groups of eczema
      patients were studied. One consisted of 18 subjects with a contact allergy to two
      fragrance substances and the other was a control group of 15 subjects allergic to
      only one of the same two fragrance substances. The test and matched control
      subject were patch tested in exactly the same way with two allergens applied in
      serial dilution in separate chambers on one side and combined in one chamber on
      the other side of the upper back. The assessment of reactions was carried out on
      day 3 by clinical grading and laser Doppler flowmetry, and the extent of the
      reaction was measured in millimetres. The data were analysed by logistic dose
      response models. It was found that the combination of two allergens in
      individuals allergic to both substances had a synergistic effect on the
      elicitation response evaluated by all three methods. The 1 : 1 mixtures of the
      two allergens elicited responses as if the doses were three to four times higher
      than those actually used, which is significantly more than expected if an
      additive effect had been present. In the control group, no increased response was
      seen to the combined allergens compared with the allergens tested separately. The
      synergistic effect demonstrated is likely to apply to other contact allergens as
      well and should be taken into account in designing diagnostic tests and
      performing safety assessments.

PMID- 9767241
TI  - Treatment of venous leg ulcers with cryopreserved cultured allogeneic
      keratinocytes: a prospective open controlled study.
AB  - Twenty-seven patients with chronic venous leg ulcers were assigned to two
      treatment groups. Fifteen were treated with cryopreserved cultured allogeneic
      keratinocyte sheets and compression bandages and 12 with compression only. The
      observation time was 8 weeks and the keratinocyte grafting procedure was
      performed once weekly. The mean reduction of the initial wound area was 35% in
      the treatment group and 14% in the control group. This difference was not
      significant. The poor effect on wound healing given by the cryopreserved
      allogeneic keratinocyte sheets contrasts with our earlier experience using fresh
      keratinocyte sheets. We believe that this is due to a weakened condition of the
      cryostored cells, as we have shown a loss in protein synthesis capacity of at
      least 50%.

PMID- 9767242
TI  - The incidence and prognosis of nail apparatus melanoma. A retrospective study of
      105 patients in four English regions.
AB  - Our population-based study establishes epidemiological data on age-specific
      incidence rates, clinical presentation, Breslow microstaging, treatment and
      survival of nail apparatus melanoma (NAM) patients in England. Four cancer
      registries, covering a population of 10.6 million, recorded 105 cases of NAM
      during the period 1984-93. During the same decade there was a total of 7585
      patients with cutaneous melanoma and NAM represents 1.4% of all cutaneous
      melanoma. The incidence rate of NAM in English patients is 0.1 per 100,000 of the
      population per annum. Amelanotic melanoma was the clinical presentation in 24 of
      our NAM cases. The overall prognosis is poor with an observed 5 year survival of
      only 51%. Patients with NAM less than 2.5 mm Breslow depth have a 5 year survival
      of 88% and are twice as likely to survive compared with those with tumours
      greater or equal to 2.5 mm in thickness (P < 0. 05). NAM patients are best
      managed by a multidisciplinary team approach in a few key skin cancer centres.

PMID- 9767243
TI  - Sun awareness in school teachers.
AB  - School children are important targets for sun awareness education, but the
      knowledge, attitudes and behaviour of school teachers with respect to sun
      awareness are poorly understood. A questionnaire-based survey of 76 school
      teachers was undertaken. Twenty-four per cent of teachers indicated previous
      experience in teaching sun awareness, but 93% of teachers had no classroom
      resources for teaching sun awareness. Sun awareness was perceived by respondents
      as unimportant relative to other health education issues. There was considerable
      scope for improvement in attitudes and behaviour of teachers with respect to sun
      awareness. Teachers need more information about environmental factors which
      affect strength of sunlight, individual risk factors for sunburn and sunscreen
      strength. Intervention strategies involving school teachers need simple messages,
      emphasizing the importance of shade, clothing and hats in sun avoidance.

PMID- 9767244
TI  - Long-term outcome of severe chronic plaque psoriasis following treatment with
      high-dose topical calcipotriol.
AB  - We have previously reported the effectiveness of high-dose calcipotriol in
      extensive psoriasis. We now report the long-term outcome in patients following
      this treatment. Twenty-eight patients with severe psoriasis were treated as in
      patients with high-dose topical calcipotriol for 2 weeks. There was a mean
      reduction in the psoriasis area and severity index of 65%. Sixty-nine per cent
      were controlled for 3 months and 42% for 6 months. The relapse rate was
      comparable with that following Ingram's regimen, the in-patient stay was shorter
      and the treatment more acceptable. Careful monitoring of calcium homeostasis is
      mandatory.

PMID- 9767245
TI  - Pigmented primary carcinoma of the breast: a clinical mimic of malignant
      melanoma.
AB  - A 68-year-old man had a pigmented tumour in the breast. Although the clinical
      picture suggested a malignant melanoma, histology revealed that the tumour was a
      primary ductal carcinoma of the breast. There was no pagetoid cell proliferation
      in the epidermis. However, tumour nests contained numerous dendritic melanocytes
      that could survive in the tumour nests without the existence of epidermal
      keratinocytes. Further immunohistochemical study employing antibodies to
      melanocyte growth factors demonstrated that anti-basic fibroblast growth factor
      (bFGF) antibody was the only reagent to show a positive staining for tumour
      cells. This indicated that the breast cancer cells produced bFGF, which enabled
      survival of melanocytes within the tumour mass.

PMID- 9767246
TI  - Merkel cell carcinoma, Bowen's disease and chronic occupational arsenic
      poisoning.
AB  - We diagnosed a unique case of Merkel cell carcinoma (MCC) coexisting with Bowen's
      disease on the sole of the foot of a 72-year-old man who had worked for about 4
      years in a factory handling inorganic arsenic. He had a past history of arsenical
      keratosis and multiple Bowen's disease. The tumour first appeared as a reddish
      macule and then showed marked growth over the next month. The tumour was excised
      and the specimen was examined histopathologically. The tumour consisted of two
      components: a group of atypical cells representing Bowen's disease in the
      epidermis and another group of atypical cells with a trabecular pattern
      characteristic of MCC in the dermis. Neither group of cells showed transitional
      findings, and the tumour elements were divided by a clear basement membrane. The
      tumour cells in the dermis were positive for neurone-specific enolase, and on
      electron microscopy had dense core granules in the cytoplasm. Inorganic arsenic
      can cause various cutaneous neoplasms, but to our knowledge, this is the first
      report of a case of MCC associated with Bowen's disease.

PMID- 9767247
TI  - Acute infiltration by non-Hodgkin's B-cell lymphoma of lesions of disseminated
      herpes zoster.
AB  - A man with a 15-year history of non-Hodgkin's lymphoma presented with
      disseminated herpes zoster which initially responded to aciclovir. This was
      shortly followed by an acute exacerbation in the sites previously affected which
      was apparently resistant to antiviral therapy. Biopsy revealed a dense
      monomorphic lymphocytic infiltrate below active herpes zoster which had the same
      morphology and immunoreactivity as the underlying lymphoma. His clinical
      condition resolved with further chemotherapy for his lymphoma and continued
      treatment with aciclovir.

PMID- 9767248
TI  - Peripheral nervous system involvement in a patient with large T-cell lymphoma
      arising from a pre-existing mycosis fungoides.
AB  - A 29-year-old man was examined for disseminated erythematous scaling patches and
      plaques and reddish, partially ulcerated nodules. Histological examination showed
      a dense, diffuse, epidermotropic infiltrate located in the entire dermis to the
      subcutaneous tissue, composed mainly of large pleomorphic T lymphocytes.
      Immunohistochemistry revealed positivity of neoplastic cells for T-cell
      associated markers, negativity for CD30 antigen and for B-cell markers.
      Polymerase chain reaction analysis detected a clonal amplification of T-cell
      receptor gamma. Based on clinicopathological and molecular findings, the
      diagnosis of large T-cell lymphoma (LCL) arising from a pre-existing mycosis
      fungoides was made. Seven months after primary diagnosis, meningeal and
      peripheral nervous system involvement developed with no other evidence of
      systemic disease. Despite chemotherapy and radiation therapy, the patient died 3
      months after the diagnosis of nervous system involvement. In patients with
      cutaneous LCL, mild neurological symptoms may precede the complete diagnostic
      picture by some weeks. A rapid and fatal progression characterizes the clinical
      course of the disease.

PMID- 9767249
TI  - Detection of anti-type VII collagen antibody in Sjogren's syndrome/lupus
      erythematosus overlap syndrome with transient bullous systemic lupus
      erythematosus.
AB  - Bullous systemic lupus erythematosus (SLE) is a chronic, widespread, non
      scarring, subepidermal blistering eruption associated with autoimmunity to type
      VII collagen. We describe a patient with Sj ogren's syndrome/lupus erythematosus
      overlap syndrome who showed transient blistering eruptions over limited skin
      surface and in oral mucosa. At the time of aggravation, the patient's serum
      contained IgG autoantibodies that bound to the dermal side of 1 mol/L NaCl-split
      normal skin, as determined by an indirect immunofluorescence test, and that
      reacted to type VII collagen, as determined by immunoblotting on dermal extract.
      Our observations suggest that a chronic, widespread, blistering eruption is not a
      prerequisite for the diagnosis of bullous SLE, and a mild, transient, blistering
      eruption could be a manifestation of type I bullous SLE.

PMID- 9767250
TI  - Linear cutaneous lupus erythematosus following the lines of Blaschko.
AB  - We describe two Japanese girls with discoid lupus erythematosus (DLE) in whom the
      condition showed a linear configuration following the lines of Blaschko. The
      clinical appearance was unusual but histological examination established the
      diagnosis. After reviewing the previous reports, we found that in six of eight
      patients with linear 'discoid' lesions, the age at onset was under 14 years; no
      patient has progressed to systemic lupus erythematosus. Patients with 'linear'
      DLE may compose a certain clinical subset. We propose the term 'linear cutaneous
      lupus erythematosus' which may be more suitable for the linear lesions of DLE.

PMID- 9767251
TI  - Recurrent aciclovir-resistant herpes simplex in a child with Wiskott-Aldrich
      syndrome.
AB  - A boy with Wiskott-Aldrich syndrome suffered from thymidine kinase (TK)-altered
      and aciclovir-resistant herpes simplex virus type 1 (HSV-1) skin infections. He
      presented with severe herpes simplex around the left eye in March 1993 at the age
      of 8 years. HSV-1 strain TAS was isolated and was shown to be susceptible to
      aciclovir (50% inhibitory concentration (IC50) 0.23 microg/mL). He was treated
      with intravenous (i.v.) high dose aciclovir, 2 mg/kg per h, which produced an
      improvement. About 1 year later (May 1994), a severe herpes simplex infection
      appeared on his face, arm, genitalia, back and foot. Treatment with i.v.
      aciclovir, 2 mg/kg per h, was initiated, but the skin lesions did not improve.
      HSV-1 strain TAR was isolated and was shown to be resistant to aciclovir (IC50 36
      microg/mL). HSV-1 TAR and TAS were susceptible to vidarabine (IC50 4. 4 and 2.9
      microg/mL, respectively). The skin lesions were treated with i.v. vidarabine, 15
      20 mg/kg per day, and healed satisfactorily. However, in March 1995, the patient
      again experienced a severe herpes simplex infection around the left eye. HSV-1
      strain R95 was isolated and was shown to be resistant to aciclovir (IC50 36
      microg/mL). Diminished sensitivity of HSV-1 TAR and R95 to aciclovir was
      associated with reduced viral TK activity and loss of aciclovir phosphorylation
      activity.

PMID- 9767252
TI  - Creeping eruption caused by a larva of the suborder Spirurina type X.
AB  - We report a 40-year-old Japanese man with a creeping eruption caused by a larva
      of the nematode suborder Spirurina type X. He had eaten raw small squid
      (hotaruika) 4 weeks before the serpiginous erythematous eruption appeared on his
      abdomen. Routine laboratory tests revealed only slight eosinophilia in his
      peripheral blood. Although we could not find the larva in an excised skin
      specimen, an indirect immunofluorescence test confirmed the presence of
      antibodies against larvae of the suborder Spirurina type X. We review 28 reported
      cases in Japan which showed that creeping eruption caused by larvae of the
      suborder Spirurina type X has the following clinical characteristics: an
      incubation time of 1-4 weeks; a migratory, well-defined, narrow, serpiginous
      erythematous eruption; and only slight peripheral blood eosinophilia. Excision of
      the advancing end of the track was curative in our patient.

PMID- 9767253
TI  - Chronic staphylococcal scalded skin syndrome.
AB  - Staphylococcal scalded skin syndrome (SSSS), not previously recorded as a chronic
      disease, persisted for 2 years in a 50-year-old woman with epilepsy and
      cerebellar ataxia. Lesions initially suggestive of erythema multiforme and toxic
      epidermal necrolysis evolved over 2 years into those typical for SSSS, with
      extensive erosions and subcorneal blisters, showing an epidermal split at the
      granular cell layer. Exfoliatin A-producing phage I-III Staphylococcus aureus,
      previously linked only to acute mild adult cases of SSSS, was cultured from
      purulent discharge in the patient's eyes, ears and open skin lesions. The roles
      of epilepsy and antiepileptic medications are discussed as possible predisposing
      factors.

PMID- 9767255
TI  - Topical melatonin in combination with vitamins E and C protects skin from
      ultraviolet-induced erythema: a human study in vivo.
AB  - In this randomized, double-blind human study, the short-term photoprotective
      effects of different antioxidants and their combinations were evaluated in vivo.
      Vitamin C (ascorbic acid), vitamin E (alpha-tocopherol) and melatonin (N-acetyl-5
      methoxytryptamine) were topically applied, alone or in combination, 30 min before
      ultraviolet-irradiation of the skin. The erythemal reaction was evaluated
      visually and non-invasively using different bioengineering methods (skin colour
      and skin blood flow). The results showed a modest protective effect of the
      vitamins when applied alone and a dose-dependent photoprotective effect of
      melatonin. Topical application of combinations of both vitamins, or of melatonin
      with vitamins, enhanced the photoprotective response. Better protection was
      obtained by using the combination of melatonin with both vitamins. The role of
      reactive oxygen species and oxygen-derived free radicals, as well as potential
      sunscreening properties of the employed antioxidants, are discussed in view of
      possible mechanisms to explain this elevated photoprotective effect.

PMID- 9767256
TI  - Correspondence 

PMID- 9767254
TI  - E210K mutation in the gene encoding the beta3 chain of laminin-5 (LAMB3) is
      predictive of a phenotype of generalized atrophic benign epidermolysis bullosa.
AB  - Pathogenetic mutations in the genes encoding the hemidesmosome-anchoring filament
      complex proteins, laminin-5 and the 180 kDa bullous pemphigoid antigen, have been
      identified in patients with the inherited mechanobullous disease, junctional
      epidermolysis bullosa (EB). Furthermore, there is some evidence to suggest that
      precise definition of the nature of mutations in these genes may correlate to
      specific phenotypes of disease. We report three junctional EB patients who carry
      an identical missense mutation, E210K, on one allele of the gene encoding the
      beta3 subunit chain of laminin-5 (LAMB3) in addition to different nonsense
      mutations on the second allele. Two of the patients are adults and display a
      specific phenotype of non-lethal junctional EB known as generalized atrophic
      benign EB, which is associated with trauma-induced blisters, nail dystrophy and
      alopecia. As the third patient is a young child with fewer features of this
      subtype to date, identification of E210K in combination with a nonsense LAMB3
      mutation may be predictive of the subsequent development of a generalized
      atrophic benign EB phenotype both in this child and in other junctional EB
      patients with the E210K mutation. Identification of this particular mutation has
      important implications for clinical management and counselling.

PMID- 9767257
TI  - Lack of mutation in the INK4a locus in basal cell carcinomas.

PMID- 9767258
TI  - Hypopigmented mycosis fungoides in a light-skinned woman.

PMID- 9767259
TI  - Disseminated pagetoid reticulosis: response to bath PUVA.

PMID- 9767260
TI  - Cutaneous metastases from carcinoma of the nasopharynx.

PMID- 9767261
TI  - The treatment of Merkel cell carcinoma and its association with
      immunosuppression.

PMID- 9767262
TI  - The Koebner phenomenon in Kaposi's sarcoma in a renal transplant recipient.

PMID- 9767263
TI  - The management of seborrhoeic keratoses by general practitioners, surgeons and
      dermatologists.

PMID- 9767264
TI  - Dormant melanocytes in the dermis: do dermal melanocytes of acquired dermal
      melanocytosis exist from birth?

PMID- 9767265
TI  - Lichen planus following hepatitis B vaccination.

PMID- 9767266
TI  - Pyoderma gangrenosum, polyarthritis and lung cysts with novel antineutrophil
      cytoplasmic antibodies to azurocidin.

PMID- 9767267
TI  - Neutrophilic eccrine hidradenitis induced by granulocyte colony-stimulating
      factor.

PMID- 9767268
TI  - Leuconychia in reflex sympathetic dystrophy: a chance association?

PMID- 9767269
TI  - Mycophenolate mofetil for psoriasis.

PMID- 9767270
TI  - Streptococcal cellulitis in reticulate lymphoedema selectively affects the
      lymphoedematous herniations.

PMID- 9767271
TI  - Pseudomonas aeruginosa folliculitis: a sporadic case from use of a contaminated
      sponge.

PMID- 9767273
TI  - St John's institute annual consultants and registrars advanced course in
      dermatology 12-14 february 1999, london, U.K 

PMID- 9767272
TI  - Diseases of the hair and scalp 

PMID- 9767275
TI  - Varma S, lanigan SW. Pseudoporphyria caused by nabumetone. Br J dermatol 1998;
      138: 549-50 

PMID- 9767274
TI  - Study day in occupational dermatoses, 26 november 1998, St John's institute of
      dermatology, london, U.K 

PMID- 9767276
TI  - Skov L et al. Contrasting effects of ultraviolet-A1 and ultraviolet-B exposure on
      the induction of TNF-alpha in human skin. Br J dermatol 1998; 138: 216-20 

PMID- 9767277
TI  - Editor's choice 

PMID- 9767278
TI  - Immunoreactivity of bullous pemphigoid (BP) autoantibodies against the NC16A and
      C-terminal domains of the 180 kDa BP antigen (BP180): immunoblot analysis and
      enzyme-linked immunosorbent assay using BP180 recombinant proteins.
AB  - The 180 kDa bullous pemphigoid (BP) antigen (BP180) is known to be recognized by
      sera from patients with BP, herpes gestationis (HG) and cicatricial pemphigoid
      (CP). A series of previous studies using BP180 recombinant proteins has shown
      that most sera from patients with BP and HG react with the NC16A domain of BP180,
      an extracellular non-collagenous region just adjacent to the plasma membrane. In
      contrast, the C-terminal region of BP180 has been reported to be one of the
      epitopes of CP. In the present study, we examined the immunoreactivity of 110 BP
      sera against the NC16A and C-terminal domains of BP180 using immunoblot analysis
      and enzyme-linked immunosorbent assay (ELISA). Immunoblot analysis revealed that
      100 (91%) and 26 (23.5%) of the 110 BP sera recognized the NC16A and C-terminal
      domains, respectively. The results of the ELISA were correlated with those of
      immunoblotting. There were no specific or significant clinical features such as
      severe involvement of mucous membranes and scarring in BP patients whose sera
      reacted with the C-terminal region. These findings suggest that some BP sera
      react with the C-terminal region of BP180 without any association with the
      characteristic clinical features of CP.

PMID- 9767279
TI  - Expression of the alpha1-alpha6 collagen IV chains in the dermoepidermal junction
      during human foetal skin development: temporal and spatial expression of the
      alpha4 collagen IV chain in an early stage of development.
AB  - To study the expression of the alpha1-alpha6 chains of type IV collagen in the
      dermoepidermal junction (DEJ) during human foetal skin development, human foetal
      (10 and 20 weeks of gestation) and adult skin was immunostained with specific
      monoclonal antibodies to the alpha1-alpha6 chains of type IV collagen. Intense
      expression of the alpha4 chain and weak expression of the alpha2 and alpha6
      chains were observed in the DEJ of 10 weeks gestational skin. In contrast, the
      alpha1, alpha2, alpha5 and alpha6 chains were detected in the DEJ of 20 weeks
      gestational and adult skin. Preferential expression of alpha4 during the early
      phase of development (10 weeks of gestation) may suggest a chain-specific
      regulatory mechanism for type IV collagen expression and its potential role in
      DEJ formation during development.

PMID- 9767280
TI  - Altered expression of the alpha2 laminin chain in psoriatic skin: the effect of
      treatment with cyclosporin.
AB  - The histopathological pattern of psoriasis is characterized by dermal
      inflammatory reaction and hyperproliferation of the epidermis. The mechanism of
      the epidermal hyperproliferation is not completely understood, but it is probably
      modulated by the basal lamina (BL), the alterations of which have not been
      described. We performed the present study to evaluate the expression of the
      alpha1, alpha2, beta1 and gamma1 laminin chains and collagen IV in the BL of
      active psoriasis vulgaris before and after cyclosporin treatment administered
      until the psoriasis was in remission. The results showed that the alpha2 chain is
      weak and irregular in the lesions, while the alpha1, beta1 and gamma1 chains and
      collagen IV are normal, with intense and continuous reaction. In the same
      subjects, this alteration was absent in skin that was clinically unaffected.
      After treatment with cyclosporin, the altered expression of the alpha2 chain
      returned to normal in the healing lesions.

PMID- 9767281
TI  - The antipsoriatic agent dimethylfumarate immunomodulates T-cell cytokine
      secretion and inhibits cytokines of the psoriatic cytokine network.
AB  - Interactions between infiltrating T cells and keratinocytes via the secretion of
      the TH1 cytokines interleukin (IL) 2 and interferon gamma (INF-gamma), the
      keratinocyte growth factor transforming growth factor alpha (TGF-alpha) and the
      cytokines IL-6 and IL-8 are thought to be the predominant mechanisms inducing
      skin lesions in psoriatic patients. Systemic treatment of psoriasis with fumaric
      acid derivatives (FAEs) has been reported to be effective in the treatment of
      psoriasis, but the mode of action is still unknown. To clarify this phenomenon,
      keratinocytes from psoriatic patients as well as from healthy volunteers were
      mono- and cocultured with HUT 78 T cells with/without the addition of FAEs; the
      cytokine concentrations were then measured in the culture supernatants.
      Furthermore, mRNA expression was determined in epidermal growth factor (EGF) 
      activated keratinocytes as well as in phytohaemagglutinin (PHA)-activated HUT 78
      T cells. Only dimethylfumarate (DMF) diminished IL-6 and TGF-alpha secretion in
      the psoriatic cocultures. However, it did not have this effect on cocultures from
      control subjects or on monocultures. DMF suppresses EGF-induced TGF-alpha mRNA
      induction in psoriatic keratinocytes. DMF inhibited INF-gamma secretion in all
      cultures but stimulated the IL-10 secretion. This immunomodulation away from the
      TH1 cytokine IFN-gamma to the TH2 cytokine IL-10 was confirmed in HUT 78 T cells
      by Northern blot analysis. An increased number of eosinophils is a known side
      effect in patients treated with this drug, suggesting a clinical relevance of
      this immunomodulation in vivo. This immunomodulation and the suppression of
      cytokines from the psoriatic cytokine network could be responsible for the
      beneficial effect of DMF in the treatment of a hyperproliferative and TH1
      cytokine-mediated skin disease.

PMID- 9767282
TI  - Investigation on a novel and specific leukotriene B4 receptor antagonist in the
      treatment of stable plaque psoriasis.
AB  - The aim of the present study was to investigate the efficacy and clinical
      tolerability of the specific leukotriene B4 receptor antagonist VML295 in the
      treatment of stable plaque psoriasis. Immunohistochemical and flow cytometrical
      methods were used to assess the effects on inflammation and epidermal
      proliferation. VML295 in the treatment of chronic plaque psoriasis was shown to
      be safe and well tolerated. After treatment, there was a statistically
      significant difference between patients treated with VML295 and patients treated
      with placebo with respect to the leukotriene B4-induced CD11b up-regulation on
      the cell surface of polymorphonuclear leukocytes derived from peripheral blood.
      Ex vivo CD11b up-regulation in the VML295-treated group was completely inhibited
      after 7 days of treatment (P = 0.001). This effect persisted until the end of the
      treatment period (P = 0.004 on day 15 and P < 0.0001 after 4 weeks), whereas
      CD11b up-regulation in the placebo group remained unaffected. There was no
      statistically significant difference in the median psoriasis area and severity
      index between the treatment groups at the end of the treatment period. During
      treatment, no significant histological changes were observed in the markers for
      cutaneous inflammation and epidermal proliferation. Although not statistically
      significant, a tendency for the increased expression of some markers of cutaneous
      inflammation and epidermal proliferation was observed after 1 week of treatment
      with VML295, and a decreased expression of these markers was seen after 4 weeks
      of treatment with VML295. This observation could indicate anti-inflammatory
      effects of VML295 appearing between 2 and 4 weeks after the start of treatment.

PMID- 9767283
TI  - Nerve-induced histamine release is of little importance in psoriatic skin.
AB  - Psoriatic plaques contain an increased number of mast cells. Both the histamine
      concentration and release are increased in lesional skin but the underlying
      mechanisms are unclear. One hypothesis is that neuropeptides transmitted from
      thin sensory cutaneous nerves continuously stimulate mast cell release of
      histamine. The aim of this study was to test this hypothesis by examining if
      topical anaesthesia of these nerves inhibits histamine release in psoriatic skin.
      The concentration of histamine was measured in microdialysates obtained from
      lesional and non-lesional skin before and during topical anaesthesia.
      Concomitantly skin blood flow was measured with scanning laser Doppler
      (perfusion) and/or 133Xe clearance (flow) techniques in the microdialysis area.
      The histamine concentrations (mean +/- SEM) were 34 +/- 4 (n = 21), 14 +/- 1.5 (n
      = 18) (P < 0. 001) and 2.8 +/- 1 nmol/L (n = 10) in lesional and non-lesional
      skin and plasma, respectively. After anaesthesia of the microdialysis areas the
      histamine concentration in psoriatic skin increased to 44 +/- 4 nmol/L (n = 19, P
      < 0.05), but remained unaltered in uninvolved skin. In anaesthetized lesional
      skin the perfusion decreased from 3.7 +/- 0.2 to 2.5 +/- 0.3 V and blood flow
      decreased from 14 +/- 5 to 9 +/- 1 mL/min per 100 g (P < 0.001, n = 10). The
      calculated release of dermal histamine in involved skin (198 +/- 30 pmol/min per
      100 g, n = 10) remained unchanged after local anaesthesia. The results indicate
      that neurogenic activation of mast cells is of minor importance for continuous
      histamine release in psoriatic skin and that the vasodilatation in the psoriatic
      plaque is not mediated by histamine.

PMID- 9767284
TI  - Narrowband ultraviolet B (TL-01) phototherapy for psoriasis: which incremental
      regimen?
AB  - Narrowband (311-313 nm) ultraviolet B phototherapy with the Philips TL-01 lamp is
      used increasingly in the treatment of psoriasis with little information available
      on the optimum irradiation regimen. We compared a high and a low incremental dose
      regimen in 20 patients with symmetrical chronic plaque psoriasis using a
      randomized half body study and thrice weekly exposures. Paired trunk, leg and arm
      plaques of psoriasis were scored blind prior to and at each treatment for
      scaling, erythema and induration. Patients were treated to clearance or minimal
      residual activity and followed up until relapse. The low increment regimen
      achieved a 10% reduction in the median cumulative dose to clearance (16,401 vs.
      18,246 mJ/cm2) with one extra treatment in 50% of the patients. However, the
      duration of treatment (median 53.5 days) was identical for both regimens except
      for one patient because there were 50% fewer episodes of erythema requiring
      postponement of treatment with the low increment regimen. We now favour the low
      increment regimen for phototherapy in our psoriasis population.

PMID- 9767285
TI  - Ultraviolet B radiation-induced production of interleukin 1alpha and interleukin
      6 in a human squamous carcinoma cell line is wavelength-dependent and can be
      inhibited by pharmacological agents.
AB  - Ultraviolet (UV) B irradiation induces keratinocytes to produce among others the
      proinflammatory cytokines interleukin (IL) 1 and IL-6. The wavelength dependence
      of this UVB effect has not yet been assessed. We evaluated the potential of
      different UVB wavelength regions to release cytokines from the squamous carcinoma
      cell line SCL II and also assessed the effect of various putative inhibitors.
      Confluent monolayers of the cells were irradiated with 0.5-2.0 mJ/cm2 UVB at 280,
      290, 300, 310 or 320 (each +/- 5) nm. In additional experiments dexamethasone (10
      9-10-5 mol/L), ascorbic acid, d-alpha-tocopherol or indomethacin (each 10-7-10-4
      mol/L) were added to the culture medium 24 h before, immediately after or
      combined before and after irradiation with 1 mJ/cm2 UVB at 280 +/- 5 nm.
      Supernatants of the cell cultures were recovered at 24 h after irradiation, and
      IL-1alpha or IL-6 were determined by an enzyme-linked immunosorbent assay
      (ELISA). IL-1alpha and IL-6 production were induced by UVB at 280, 290 and 300
      nm, the production depended on the UV dose and decreased with increasing
      wavelengths. Irradiation at 310 or 320 nm did not induce cytokine production up
      to the maximum dose used. The production of IL-1 alpha/IL-6 was inhibited up to
      80/89% (10-7-10-6 mol/L before and after irradiation) by dexamethasone in a
      concentration-dependent manner and with all conditions of incubation. Release of
      cytokines was also suppressed by indomethacin, d-alpha-tocopherol or ascorbic
      acid, but concentration dependence was not always evident. These results show
      that particularly shorter UVB radiation, which is expected to increase due to
      stratospheric ozone depletion, induces prominent production of proinflammatory
      cytokines, indicating major biological effects. Different pharmacological
      compounds can interfere with this effect and seem worth further evaluation with
      regard to their clinical effects.

PMID- 9767286
TI  - Clinically prescribed sunscreen (sun protection factor 15) does not decrease
      serum vitamin D concentration sufficiently either to induce changes in
      parathyroid function or in metabolic markers.
AB  - Some studies have suggested that the use of sunscreens to prevent skin cancer may
      put the population at risk of vitamin D deficiency. We followed 24 sunscreen
      users and 19 controls over 2 years, including two summers, two winters and a
      basal period (winter). Vitamin D, parathormone and bone biological markers were
      evaluated each season. Mean levels of 25-hydroxyvitamin D rose in summer, with
      the increments being significantly higher for the second year in the control
      group. Levels decreased in winter in both groups, and were significantly lower in
      sunscreen users. We did not observe any significant change in parathormone,
      tartrate resistant phosphatase, total alkaline phosphatase, osteocalcin, urine
      hydroxyproline or urine calcium. Clinically prescribed sunscreen creams (sun
      protection factor 15) caused a minor decrease in 25-hydroxyvitamin D levels,
      which did not induce secondary hyperparathyroidism or an increment in bone
      biological markers.

PMID- 9767287
TI  - Sunbeds in current use in Scotland: a survey of their output and patterns of use.
AB  - Spectral irradiances of 100 commercially available sunbeds in current use have
      been measured. Ultraviolet (UV) A and UVB doses from sunbed use have been
      calculated and compared with doses likely to be received from solar radiation.
      The majority of sunbeds use UVA fluorescent tubes for irradiating the body and
      filtered metal halide lamps, which have a higher proportion of UVA1, for the
      face. The average minimum erythemal dose per session is 0.80, but irradiances for
      particular models varied by a factor of two to three primarily because of decline
      in lamp output with age. The UVA dose from a session on a sunbed is similar to
      that which might be received from 20 to 30 min sunbathing at a Mediterranean
      resort or 1 h on a sunny day in Glasgow, while UVB doses are 20-25% of this
      level. Responses from 200 current users of the sunbeds indicate that 38% had skin
      types 1 and 2, that 17% had more than 100 annual sunbed sessions and that 35%
      rarely or never used the goggles provided.

PMID- 9767288
TI  - Extrafacial lentigo maligna melanoma: analysis of 71 cases and comparison with
      lentigo maligna melanoma of the head and neck.
AB  - We report a retrospective analysis of extrafacial lentigo maligna melanoma (LMM),
      and a comparison with patients with LMM of the head and neck. Seventy-one
      patients (22 men, 49 women) with extrafacial LMM were identified from the
      Scottish Melanoma Group database for January 1979-March 1996. Their mean age (63
      years) was significantly less than that of 335 patients with head and neck LMM
      (mean 72 years, P < 0.001), with a significantly greater difference among women
      than men. Extrafacial sites comprised 17.5% of LMMs. There was a marked body site
      distribution difference between the sexes (P = 0. 001): 68% of extrafacial LMMs
      in men were on the trunk while 80% in women were on the limbs, particularly the
      lower leg. Extrafacial LMMs were thinner at presentation than head and neck LMMs
      (P < 0.05) in both sexes, but this was not simply explained by the younger age of
      these patients as there was no significant correlation between age and tumour
      thickness at either extrafacial or at head and neck sites. Although the female
      lower leg is a site of chronic solar exposure in older women, the other
      extrafacial sites are habitually covered in the temperate Scottish climate. The
      significantly younger age group of patients with LMM at extrafacial compared with
      head and neck sites therefore suggests that the relationship between LMM and
      sunlight is not simply related to cumulative solar exposure. The demonstration
      that head and neck LMMs were thicker at presentation compared with extrafacial
      sites, despite being at a more routinely visible part of the body, suggests that
      there are still opportunities for targeted pigmented lesion public education.

PMID- 9767289
TI  - Morphological alterations of epidermal melanocytes in photoageing: an
      ultrastructural and cytomorphometric study.
AB  - To examine pathological changes of melanocytes in photodamaged skin, we performed
      a comparative cytomorphometric analysis and a qualitative observation of
      melanocytes from sun-exposed and sun-protected facial skin at the electron
      microscopic level. The characteristic ultrastructural features of melanocytes in
      photodamaged skin included a statistically significant increase in their number,
      a marked nuclear heterogeneity, signs of cell activation, close apposition to
      photodamaged degenerate keratinocytes, degenerative changes represented by large
      intracytoplasmic vacuoles, and frequent direct contacts with Langerhans cells.
      Cytomorphometric analysis revealed significant decreases in cell and nuclear
      sizes, increases in cell and nuclear perimeters accompanied by irregular
      contours, and higher degrees of nuclear ellipticity in sun-exposed melanocytes.
      This study demonstrates that there are remarkable differences in the morphology
      of melanocytes between photoaged and intrinsically aged facial skin, and supports
      the concept that photoageing processes contribute to cytological alterations in
      melanocytes.

PMID- 9767291
TI  - The influence of female sex hormones on skin thickness: evaluation using 20 MHz
      sonography.
AB  - Changes in skin thickness and echodensity during the spontaneous menstrual cycle,
      in women taking hormonal contraceptives and pregnant women were investigated by
      high-frequency (20 MHz) ultrasound. Women with a spontaneous ovulatory menstrual
      cycle (group I), women taking one-phase contraceptives (group II), women taking
      three-phase contraceptives (group III) and pregnant women (group IV) were
      measured at the following locations: proximal and distal forearm and lower leg on
      both sides. The skin was investigated during three phases of the menstrual cycle:
      days 2-4 (phase A), days 12-14 (phase B) and days 20-22 (phase C). Oestradiol and
      progesterone levels were determined at each phase. The pregnant women were
      investigated 2 weeks prepartal and 6 weeks after delivery. Group I showed a
      statistically significant increase in the skin thickness from phase A to phase B,
      but not from phase B to phase C. Group II showed no significant changes in skin
      thickness, whereas the skin thickness increased from phase A to phase B in group
      III. In group IV, the skin was significantly thicker prepartal than after
      delivery. The measured echodensity showed a negative correlation with skin
      thickness in group III and in pregnant women. We were able to demonstrate that
      the status of female sex hormones influences the thickness of the skin. These
      results can be explained by hormone-induced water retention in the skin.
      Sonography at 20 MHz is able to quantify these effects, which should be
      considered when performing ultrasound measurement in women.

PMID- 9767290
TI  - Epidermal Langerhans cell apoptosis is induced in vivo by nonanoic acid but not
      by sodium lauryl sulphate.
AB  - Exposure to irritants may cause chronic irritant contact dermatitis (ICD),
      characterized by irregular epidermal thickening and a predominantly dermal
      mononuclear cell infiltrate. The mechanisms involved, and why only certain
      individuals are affected, are not clearly understood. Different irritants may
      trigger different cellular and molecular interactions between resident skin cells
      and recruited inflammatory cells. In some individuals these interactions may
      become self-perpetuating resulting in persistent inflammation in the absence of
      continued exposure. This study examined Langerhans cell (LC) density in
      clinically normal skin of 46 patients with chronic ICD and 10 healthy
      individuals, and compared the action of the two irritants nonanoic acid (NA) and
      sodium lauryl sulphate (SLS) on the LCs and keratinocytes of clinically normal
      skin in patients with chronic ICD. There was a higher number of LCs/mm basement
      membrane in patients compared with controls, although there was no difference in
      the number of dendrites/LC nor in dendrite length. SLS induced keratinocyte
      proliferation after 48 h exposure, had no effect on LC number or distribution,
      and induced keratinocyte apoptosis after 24 and 48 h exposure. In contrast, NA
      decreased keratinocyte proliferation after 24 h exposure but this returned to
      basal levels after 48 h, and induced epidermal cell apoptosis after only 6 h
      exposure. NA dramatically decreased LC number after 24 and 48 h exposure, which
      was accompanied by basal redistribution and decreased dendrite length. Most
      significantly, NA induced apoptosis in over half of the LCs present after 24 and
      48 h exposure.

PMID- 9767292
TI  - The effect of long-term treatment with tacalcitol on the psoriatic epidermis. A
      flow cytometric analysis.
AB  - During the last decade, novel analogues of 1alpha,25-dihydroxy vitamin D3 have
      been developed for the treatment of psoriasis. Recently, the efficacy of short
      term treatment with the novel derivative tacalcitol (1alpha,24-dihydroxy vitamin
      D3) has been documented. However, data on the long-term effect of tacalcitol on
      psoriatic skin are sparse. In this study, we assessed the cell characteristics of
      the psoriatic epidermis after treatment with tacalcitol for up to 24 weeks. We
      investigated how long-term treatment with tacalcitol modulates the percentages of
      differentiated keratinocytes, inflammation cells and basal keratinocytes, and the
      percentage of cells in the SG2M phase in the basal cell population. From 11
      patients who were treated with tacalcitol for up to 18 months, we obtained single
      cell suspensions of a representative psoriatic lesion after 0, 8, 12, 18 and 24
      weeks of treatment. A Psoriasis Area and Severity Index was performed at each
      visit as well. Cell suspensions were stained with markers for inflammation
      (Vim3B4), differentiation (RKSE60) and proliferation (TO-PRO-3 iodide) and
      analysed flow cytometrically. Clinically, patients improved significantly after 8
      weeks of treatment. This clinical effect was preserved for the rest of the period
      of treatment with no further significant improvement. Proliferative activity also
      decreased significantly after 8 weeks of treatment. Proliferation did not show
      further significant decreases or habituation after 12, 18 and 24 weeks. For
      inflammation, no statistically reliable trends could be seen. Differentiation
      improved significantly after 8 weeks of treatment, but decreased again
      significantly after 12 weeks. In the period from 12 to 24 weeks, no further
      significant change was observed. We conclude that tacalcitol is an effective
      antipsoriatic drug. Prolonged treatment with tacalcitol will generally maintain
      improvement at the level reached after 8 weeks. Owing to the beneficial effect on
      both clinical state and proliferation, tacalcitol is likely to be an adequate
      maintenance therapy.

PMID- 9767293
TI  - BAX protein is not expressed by basal cell carcinomas.
AB  - BAX and related proteins encoded by the BCL2 gene family are involved in the
      regulation of apoptosis. BAX is an apoptosis-promoting protein. The slow growth
      of basal cell carcinoma (BCC) has so far been explained by a high apoptotic
      activity. We investigated immunohistochemically 27 BCCs for expression of the
      apoptosis-promoting BAX protein. BCC did not express detectable amounts of BAX
      immunohistochemically. The results indicate that apoptosis in BCC does not
      involve BAX protein. We propose that the apoptotic pathway in BCC is regulated by
      either less common members of the BCL2 gene family or bypasses the regulation of
      the BCL2 gene family.

PMID- 9767294
TI  - Keratin 17 mutations cause either steatocystoma multiplex or pachyonychia
      congenita type 2.
AB  - Pachyonychia congenita type 2 (PC-2; Jackson-Lawler syndrome) is an autosomal
      dominant disorder characterized by hypertrophic nail dystrophy, mild focal
      keratoderma, multiple pilosebaceous cysts and other features of ectodermal
      dysplasia. Keratin 17 (K17) is a differentiation-specific keratin expressed in
      the nail bed, hair follicle, sebaceous gland and other epidermal appendages.
      Previously, we have demonstrated that PC-2 is caused by mutations in K17 and that
      similar mutations in this gene can present as steatocystoma multiplex with little
      or no nail dystrophy. Here, we describe three unrelated kindreds carrying K17
      mutations. Two of these families have identical missense mutations (R94C) in the
      1A domain of K17. However, while affected members of one kindred have the
      classical features of PC-2, affected persons in the other family have the
      steatocystoma multiplex phenotype. In a third family with PC-2, mutation N92S was
      detected, bringing the total number of distinct mutations reported in K17 thus
      far to 11. These results demonstrate that K17 mutations commonly underlie both PC
      2 and steatocystoma multiplex and that the alternate phenotypes which arise from
      these genetic lesions in K17 are independent of the specific mutation involved.

PMID- 9767295
TI  - Cutaneous presentation of nasal/nasal type T/NK cell lymphoma:
      clinicopathological findings of four cases.
AB  - Epstein-Barr virus (EBV)-associated T/natural killer (NK) cell lymphoma mainly
      shows nasal lesions, and has recently been shown to be associated with cutaneous
      T-cell lymphoma (CTCL). The detailed features of CTCL nasal metastasis have yet
      to be elucidated. We report clinicopathological findings for four cases of
      cutaneous T/NK cell lymphoma with metastasis to the nose. The four patients
      presented progressive involvement of nasal lesions of CTCL, an aggressive course
      and poor outcome. Their pathological and immunohistological findings were
      consistent with peripheral T/NK cell neoplasm and, in three of four cases, EBER-1
      were apparently detected in lymphoma cells by in situ hybridization, and two of
      four cases were also positive for TIA-1. The polymerase chain reaction (PCR)
      results showed the identical band from the skin and nasal lesions of the two
      patients. We also reviewed the cases of similar clinical course and attempted to
      elucidate clinical, pathological, immunological and genotypic features. The 10
      reported cutaneous T/NK cell lymphomas with nasal metastasis revealed a poor
      prognosis (nine of 10 died at 3-108 months). Six cases of nine showed a positive
      reaction to EBV, and six cases revealed T-cell receptor beta or -gamma
      rearrangement. These findings suggest that most cutaneous T/NK cell lymphoma with
      nasal metastasis are similar to nasal T-cell lymphoma associated with EBV
      infection. This type of cutaneous T/NK cell lymphoma likely to involve nasal
      lesions and skin cases seemed to have a poor prognosis.

PMID- 9767296
TI  - Iatrogenic isolated isoleucine deficiency as the cause of an acrodermatitis
      enteropathica-like syndrome.
AB  - We present two patients with a suspected inborn error of metabolism. A female
      newborn presented with dysmorphic features and convulsions. Metabolic screening
      suggested a defect in isoleucine degradation. Within 2 weeks after the
      introduction of an isoleucine-restricted diet, she developed a severe
      acrodermatitis enteropathica-like syndrome. The plasma level of isoleucine was
      low with a normal leucine/isoleucine ratio. The second patient, a female infant
      deficient in leucine as a result of a leucine-restricted diet, did not develop a
      dermatosis. Isoleucine is essential for normal growth and differentiation of
      keratinocytes and enterocytes. Deficiency of isoleucine, and not leucine or an
      imbalance in the leucine/isoleucine ratio, may result in an acrodermatitis
      enteropathica-like syndrome.

PMID- 9767297
TI  - Localized peeling skin syndrome: case report with ultrastructural study.
AB  - We report a young woman in whom the history, clinical features, histopathological
      and ultrastructural findings led to a diagnosis of peeling skin syndrome (PSS).
      PSS is a rare and not well classified genodermatosis, mainly characterized by the
      spontaneous separation of the stratum corneum from the stratum granulosum. The
      unusual feature in our patient was the strict localization to the palm. PSS has
      been described as a more generalized disease frequently sparing palms and soles.
      We propose the diagnosis label of 'localized PSS' for this previously undescribed
      variant of a rare keratinization defect.

PMID- 9767298
TI  - Juvenile pemphigus foliaceus.
AB  - A 7-year-old girl with generalized erythematous, scaling plaques and
      vesiculobullous lesions on the extremities was diagnosed as having pemphigus
      foliaceus. Lesional direct immunofluorescence revealed intercellular IgG, IgA and
      C3 deposition. The patient's serum gave positive reactions against one epitope of
      desmoglein 3 and the epitope of desmoglein 1 in enzyme-linked immunosorbent
      assays, but the blood sample for indirect immunofluorescence did not display any
      circulating antibodies. The patient was successfully treated systemically with
      prednisolone and dapsone. Currently, she is taking dapsone, 12.5 mg daily. She
      has been free of lesions for the last 3 years.

PMID- 9767299
TI  - Neonatal pemphigus vulgaris associated with mild oral pemphigus vulgaris in the
      mother during pregnancy.
AB  - We report a neonate with immunofluorescence-proven pemphigus vulgaris. The
      condition presented at birth with widespread skin erosions and ulceration of the
      oral mucosa. Histopathological and immunofluorescence studies confirmed pemphigus
      vulgaris. The mother had mild oral pemphigus vulgaris treated during pregnancy
      with topical corticosteroids. All the neonate's skin erosions had crust formation
      at day 2 but healed completely within 2 weeks.

PMID- 9767300
TI  - An unusual reaction to cold: a sporadic case of familial polymorphous cold
      eruption?
AB  - A 14-year-old Japanese girl had a lifelong history of skin lesions developing
      after generalized exposure to cold air; the lesions were often accompanied by
      systemic symptoms such as fever and chills. The skin lesions were non-pruritic,
      maculopapular, erythematous eruptions and were neither urticarial nor
      angioedematous. An ice-cube test was negative. Laboratory examinations showed
      marked leucocytosis during an acute attack. On the basis of clinical features,
      histological findings and laboratory data, although these symptoms were sporadic,
      the most likely diagnosis was familial polymorphous cold eruption, which has also
      been referred to as familial cold urticaria. Serum levels of granulocyte colony
      stimulating factor and interleukin 6 were significantly elevated during an acute
      attack after cold exposure, suggesting that both cytokines played important parts
      in the development of her condition.

PMID- 9767301
TI  - Autoimmune progesterone dermatitis: treatment with oophorectomy.
AB  - Autoimmune progesterone dermatitis is a rare manifestation of hypersensitivity to
      endogenous hormones with polymorphic clinical manifestations. We report a 28-year
      old woman with a 5-year history of mucocutaneous erythema multiforme occurring
      cyclically in the premenstrual period. Progesterone sensitivity was demonstrated
      by challenge test with medroxyprogesterone acetate. Treatments with oestrogens,
      tamoxifen and triptorelin had to be withdrawn because of intolerable adverse
      effects. Oophorectomy finally cured the disease.

PMID- 9767302
TI  - Distal digital keratoacanthoma: a report of 12 cases and a review of the
      literature.
AB  - Twelve cases of distal digital keratoacanthoma (DKA) affecting the subungual area
      or the proximal nail fold are reported. The distal phalanx of the toe was
      affected in three cases. Spontaneous resolution occurred in one; one other
      recurred after surgery. We also discuss the link between DKA and incontinentia
      pigmenti subungual tumours; these entities are indistinguishable.

PMID- 9767304
TI  - Ecthyma gangrenosum-like eruption associated with Morganella morganii infection.
AB  - Ecthyma gangrenosum is considered as a pathognomonic sign of Pseudomonas
      aeruginosa sepsis. Lesions similar to ecthyma gangrenosum may be caused by other
      organisms. We report a case of an ecthyma gangrenosum-like eruption caused by
      Morganella morganii, a Gram-negative bacillus.

PMID- 9767303
TI  - Progressive HHV-8-positive classic Kaposi's sarcoma: rapid response to interferon
      alpha-2a but persistence of HHV-8 DNA sequences in lesional skin.
AB  - The pathogenesis of Kaposi's sarcoma (KS) is often attributed to an infectious
      agent. In particular, the human herpesvirus 8 (HHV-8) was currently shown to be
      closely related to all known KS types, including HIV-associated KS, European
      classic KS, African endemic KS and iatrogenic KS. We report here on an HIV
      negative, German patient of neither Jewish nor Mediterranean descent with
      disseminated classic KS showing unusual rapid progression into the tumour stage.
      After systemic administration of interferon alpha-2a over 4 weeks all tumour
      lesions cleared completely. Interestingly, HHV-8 DNA sequences detected by nested
      polymerase chain reaction in KS lesions before the onset of treatment were still
      present in lesional skin after complete remission of the tumour. No recurrence
      was seen after a follow-up period of 6 months.

PMID- 9767306
TI  - HLA-Cw*0602 and HIV-associated psoriasis.
AB  - The aetiopathogenesis of psoriasis is unknown, but genetic and environmental
      factors may be involved. Psoriasis may not be one disease but a cutaneous
      inflammatory reaction pattern consequent upon several different independent or
      related stimuli in susceptible individuals. There are controversial issues
      regarding the immunological basis of psoriasis and the role of CD4 vs. CD8 T
      lymphocytes. Psoriasis has been associated with HLA-Cw6 and Cw7 by serology and
      specifically with HLA-Cw*0602 by polymerase chain reaction (PCR) typing.
      Psoriasis is probably no more common in HIV infection than in the general
      population; however, it may appear for the first time or pre-existing psoriasis
      may worsen and be difficult to treat in HIV disease. We have investigated the
      prevalence of HLA-C alleles, in the specific clinical context of HIV infection
      complicated by type 1 psoriasis, in a case control study of 14 men with HIV
      disease and type 1 psoriasis and 147 HIV-infected patients without psoriasis.
      Typing was performed using PCR with sequence-specific amplification primers.
      Eleven of 14 patients (79%) with psoriasis carried the HLA-Cw*0602 allele
      compared with 24.5% of those without psoriasis (odds ratio = 11.31; 95%
      confidence limits 2. 73 to 65.36; P = 0.0001). Two patients without the HLA
      Cw*0602 allele carried instead the closely related Cw*0401/3 allele. The results
      confirm the previously reported association between the HLA-Cw*0602 allele and
      type 1 psoriasis, and suggest that the association with HLA-Cw*0602 is stronger
      in HIV-associated psoriasis although this trend needs to be supported by a larger
      sample. The immunodysregulation resulting from HIV infection may trigger
      psoriasis in those genetically predisposed by the Cw*0602 allele. As CD8 T cells
      recognize antigens in the context of class I major histocompatibility complex,
      the identification of an HLA class I association in HIV-associated psoriasis
      strengthens the argument for an important role for CD8 + T lymphocytes in the
      immunopathogenesis of psoriasis. Investigations of the pathogenesis of psoriasis
      should take account of clinical and other subtypes already identified.

PMID- 9767305
TI  - Cutaneous aspergillosis: a report of six cases.
AB  - Skin invasion by Aspergillus is infrequent. We here describe six
      immunocompromised patients with skin manifestations caused by Aspergillus. A
      heart transplant recipient developed a primary cutaneous aspergillosis; two
      patients (one with chronic granulomatous disease and another treated with a high
      dose of corticosteroids) presented with nodular lesions secondary to
      haematogenous dissemination; and three patients with acute myelogenous leukaemia
      had skin dissemination by contiguity from orbit and sinus invasion. A. flavus was
      isolated in the three cases of leukaemia; the infection was due to A. fumigatus
      in the transplant recipient; A. fumigatus and A. versicolor were isolated in the
      patients with the secondary aspergillosis. In most cases, amphotericin B was
      useful, with clinical and mycological remission in four patients. A patient with
      leukaemia died without undergoing treatment, and a child carrier of chronic
      granulomatous disease died after only 12 days of treatment.

PMID- 9767307
TI  - Error in the original description of the psoriasis area and severity index.

PMID- 9767308
TI  - The downregulation of interleukin 1 and tumour necrosis factor receptors by
      topical tacalcitol (1,24(OH)2D3) in psoriasis.

PMID- 9767309
TI  - Increased temperature: a potentially important side-effect of ultraviolet
      radiation treatment leading to induction of interstitial collagenase/matrix
      metalloproteinase-1.

PMID- 9767310
TI  - The use of polymerase chain reaction in New World cutaneous leishmaniasis.

PMID- 9767312
TI  - Thirty-five cases of Kimura's disease (eosinophilic lymphogranuloma)

PMID- 9767311
TI  - Distribution of Merkel cells in adult human nail matrix.

PMID- 9767313
TI  - Granulomatous skin lesions in a patient with ataxia telangiectasia.

PMID- 9767314
TI  - Multiple cutaneous reticulohistiocytosis.

PMID- 9767316
TI  - Reactive perforating collagenosis associated with periampullary carcinoma.

PMID- 9767315
TI  - Verruciform xanthoma arising in an arteriovenous haemangioma.

PMID- 9767317
TI  - Papulonecrotic tuberculide complicating scrofuloderma in a health-care worker.

PMID- 9767318
TI  - Pyodermatitis-pyostomatitis vegetans: evidence for an entirely mucocutaneous
      variant.

PMID- 9767319
TI  - Acute cutaneous graft-versus-host disease with ichthyosiform features.

PMID- 9767320
TI  - Neutrophil-poor Sweet's syndrome with response to potassium iodide.

PMID- 9767321
TI  - Pyoderma gangrenosum with rheumatoid arthritis and pulmonary aseptic abscess
      responding to treatment with dapsone.

PMID- 9767322
TI  - Multiple facial eccrine hidrocystomas: effective topical therapy with atropine.

PMID- 9767323
TI  - Extracorporeal photochemotherapy in nodular scleroderma.

PMID- 9767324
TI  - Multiple scrotal lymphangiomas (lymphangiectases) treated by carbon dioxide laser
      ablation.

PMID- 9767327
TI  - Annual meeting of the british society for investigative dermatology, 7-9 april
      1999, university of wales, cardiff, UK 

PMID- 9767326
TI  - Pathology of the skin: atlas of clinical-pathological correlation 

PMID- 9767325
TI  - Treatment of minocycline-induced pigmentation with the neodymium-Yag laser.

PMID- 9767328
TI  - Clinicopathological workshop on skin diseases (Inflammatory dermatoses), 2
      october 1998, london, UK 

PMID- 9767329
TI  - Popescu CM, popescu R, williams H, forsea D. Community validation of the united
      kingdom diagnostic criteria for atopic dermatitis in romanian school children. Br
      J dermatol 1998; 138: 436-442 

PMID- 9767330
TI  - A new era in cancer prevention.

PMID- 9767331
TI  - Weight loss, skin rash, and cough following bone marrow transplantation for
      chronic myelogenous leukemia.

PMID- 9767333
TI  - Cancer screening and early detection: managing malpractice risk.
AB  - PURPOSE: The purpose of this report is to educate healthcare professionals about
      the legal risks of conducting cancer screening examinations and necessary risk
      reduction practices. OVERVIEW: The authors describe the elements of a medical
      malpractice claim, the healthcare professionals' legal standard of care, theories
      of malpractice liability, common factors related to missed or delayed diagnoses,
      malpractice defenses, and risk reduction practices. CLINICAL IMPLICATIONS:
      Healthcare professionals, including physicians, physician assistants, advanced
      practice nurses, and social workers, have been shown to be clinically effective
      in cancer screening, and early detection of many cancers leads to improved long
      term survival rates. Healthcare professionals who conduct cancer early detection
      examinations and counsel patients in cancer screening programs need to be aware
      of the common legal theories under which lawsuits are brought related to cancer
      detection examinations. Important steps in reducing the risk of malpractice
      include developing creative strategies to address the theories of liability in
      the area of cancer screening and early detection; keeping abreast of changes in
      national and international cancer screening recommendations; monitoring the
      literature for approaches to decrease liability; and scrupulously maintaining
      documentation of all findings and interactions among providers and between
      providers and patients.

PMID- 9767334
TI  - Cancer screening of older women : a primary care issue.
AB  - PURPOSE: The purpose of this retrospective chart review was to examine whether
      family practice physicians and residents were screening older women for breast,
      gynecologic, and colorectal cancers as recommended by the American Cancer
      Society, the Guide to Clinical Preventive Services, and Healthy People 2000.
      METHODS: A retrospective chart review of women 60 years and older who were seen
      at least twice between July 1, 1992, and June 30, 1993, in a midwestern family
      practice residency program was completed. From the original sample of 660
      potential subjects, a systematic random selection of every third chart was
      identified for review, resulting in a sample of 201. Analysis of the data was
      performed by descriptive statistics and chi-square tests. A series of multiple
      regression models using age, number of visits, type and gender of provider, and
      personal or family history of cancer as predictor variables was performed.
      RESULTS: Breast cancer screening was offered to approximately 70% of the sample,
      with only about one third of the older women receiving mammography or clinical
      breast examination. Recommendations for gynecologic cancer screening were given
      to 63% of the sample, with less than one third receiving Papanicolaou smears.
      Recommendations for digital rectal examination, fecal occult blood test, and
      flexible sigmoidoscopy were 58%, 59%, and 30%, respectively. The percentages of
      patients who actually received these tests were considerably lower. CLINICAL
      IMPLICATIONS: Barriers for appropriate cancer screening for older women exist for
      both the provider and the patient; however, many of these obstacles can be
      overcome. Improving the resident's exposure to the current recommendations,
      increasing geriatric content in the training program, and initiating a reminder
      system may reduce some of the provider barriers. The use of midlevel providers
      may increase the preventive services offered to older women as well as educate
      and empower these women to become responsible for their own healthcare. Together,
      physicians and midlevel providers can become patient advocates through political
      activism, encouraging legislation that guarantees payment for cancer screening
      tests. Finally, primary care providers can become actively engaged in research
      that explores the healthcare concerns of older women.

PMID- 9767335
TI  - Leptomeningeal involvement in chronic lymphocytic leukemia.
AB  - PURPOSE: This review and case report address the rare complication of
      leptomeningeal involvement in patients with chronic lymphocytic leukemia.
      OVERVIEW: Chronic lymphocytic leukemia is the most common form of leukemia, with
      more than 200,000 cases reported in the past 20 years. An uncommon complication
      of the disorder is central nervous system invasion. To date, only 21 cases have
      been reported, and their presenting symptoms have been heterogeneous and often
      nonspecific, including headache, cranial nerve abnormalities, confusion, ataxia,
      nausea, vomiting, and fever. The diagnosis is confirmed by the presence of a
      clonal population of lymphocytes in the cerebrospinal fluid. Treatment is either
      intrathecal or intraventricular chemotherapy with adjuvant radiation therapy or
      radiation alone. Prognosis is improved by prompt and aggressive therapy. In this
      case report, a 61-year-old man developed severe ataxia, vertigo, and occipital
      headaches 4 weeks after diagnosis with otherwise asymptomatic chronic lymphocytic
      leukemia. After treatment with both radiation to the head and neck and
      intrathecal methotrexate the patient achieved complete symptom resolution. Thus
      far, no additional systemic cytotoxic chemotherapy has been necessary. CLINICAL
      IMPLICATIONS: Because central nervous system invasion is uncommon in chronic
      lymphocytic leukemia, it may go undiagnosed and under-reported. Providers of
      patients with this disease need to be aware of possible central nervous system
      invasion when patients present with cranial nerve signs or symptoms and/or
      nonspecific neurologic manifestations. Early identification and prompt central
      nervous system-directed chemotherapy can affect morbidity and quality of life
      positively.

PMID- 9767336
TI  - The role of the physician as an information source on mammography.
AB  - PURPOSE: The value of mammography for asymptomatic women younger than 50 years of
      age has been under debate, and it had been suggested that each woman should
      decide for herself whether to start having mammograms in her 40s. This decision
      making process requires women to have knowledge of screening guidelines. This
      study reported key determining informational factors that led women age 40 and
      older to obtain a mammogram. DESCRIPTION OF STUDY: To examine the relationship
      between sources of information and utilization of mammography, the authors
      conducted a communitywide telephone survey, in English and Spanish, of a
      stratified random sample of 999 white, black, and Hispanic women in Dade County,
      Florida. The survey was designed to measure knowledge, attitudes, practices, and
      beliefs about breast cancer, its prevention, and its early detection. Data for
      784 women 40 years and older are analyzed and reported here. RESULTS: The most
      commonly cited source of information was the media (90.2%). In a logistic
      regression, having had a checkup in the past year was the strongest predictor of
      having had a recent mammogram as opposed to a distant one (OR 4.17; 95% CI 2.92
      5.95). Women who named their physician as an important source of information
      about health and prevention were also more likely to have had a recent
      examination (OR 1.85; 95% CI 1.27-2.69). CLINICAL IMPLICATIONS: This analysis of
      the relationship between the source of information and utilization of mammography
      suggests that physicians, as sources of information, serve to motivate women to
      obtain a mammogram. This is true even after taking into account the patient's age
      and utilization of the healthcare system for preventive care in general. For this
      reason, it is imperative that clinicians be aware of national guidelines for
      breast cancer screening; of the risks and benefits of screening measures; and of
      the implications of a positive and negative test result. In addition, clinicians
      must realize the importance of follow-up to remind the patient to obtain a
      mammogram or other screening test and should develop strategies to provide this
      service.

PMID- 9767337
TI  - The impact of radiation therapy on quality of life in patients with cancer.
AB  - PURPOSE: This study was conducted to evaluate the physical and mental status
      change during and after a course of radiation treatment in patients with cancer.
      DESCRIPTION OF STUDY: Twenty-four patients with various malignant diseases were
      enrolled, including 9 men and 15 women, whose median age was 64.5, to receive
      radiation therapy. All patients also received psychosocial support from nurses,
      social workers, and/or organized support groups. The Rand 36-item survey 1.0 (SF
      36) was completed at the beginning, the second week, the completion of treatment,
      and 1 and 3 months after treatment for the evaluation of physical component
      scores and mental component scores. Karnofsky performance scale and toxicity
      scores were determined by the treating nurses and physicians. RESULTS: The
      physical component scores of evaluated patients before treatment were
      approximately 20% lower than those of the general U.S. population, whereas mental
      component scores were similar to those of the general U.S. population. After
      treatment started, Karnofsky performance scale decreased concurrently with an
      increased rate of toxicity. Both physical and mental component scores were
      relatively stable throughout the course of evaluation. Mental component scores
      were the only predictor of toxicity during the treatment. Karnofsky performance
      scale dropped to their lowest point at the completion of treatment and then
      improved at 1-month follow-up. CLINICAL IMPLICATIONS: The patients who had higher
      mental component scores before treatment appeared to have higher, and improving,
      physical component scores throughout the course of evaluation. Along with
      complementary social support, the implementation of psychosocial support early
      and throughout the course of treatment may result in physical benefits and
      improving overall quality of life. Care should also be taken to make psychosocial
      support available to patients after the completion of treatment.

PMID- 9767338
TI  - Overview of alternative/complementary medicine.

PMID- 9767339
TI  - Bulletin board

PMID- 9767340
TI  - Practice guidelines for patients with rare cancers.

PMID- 9767341
TI  - Liposomes as drug delivery systems.

PMID- 9767342
TI  - Treating mice, caring for people.

PMID- 9767343
TI  - Multidisciplinary rounds: patient-family-staff dynamics: when the patient/family
      are colleagues.

PMID- 9767344
TI  - Influence of culture on cancer pain management in Hispanic patients.
AB  - PURPOSE: The purpose of this pilot study was to describe the influence of culture
      on cancer pain management in Hispanic (Mexican and Central American) patients.
      DESCRIPTION OF STUDY: This qualitative study is guided by the conceptual
      framework of the Pain and Quality of Life model and the Biocultural Model of
      Pain. It was developed as a companion study to a National Cancer Institute (NCI)
      funded project to disseminate a pain education program for adult patients with
      cancer and their family care givers in community home-care agencies. After
      completing the NCI study, Hispanic subjects were invited to participate in the
      qualitative companion study. A total of 17 subjects, the majority of whom were
      women, were interviewed. The Hispanic Pain Experience Questionnaire (HPEQ) was
      used to elicit answers to open-ended questions regarding the perception and
      management of cancer pain. RESULTS: Themes that emerged from the questionnaire
      were Influence of Culture, Expressions of Pain, Managing Pain/Medications, and
      Use of Nondrug Interventions. Responses suggest that culture, family beliefs, and
      religion contribute significantly to management and expression of pain by the
      patient and care giver. In addition, this group showed that pain may be
      approached with stoicism; therefore, lack of verbal or behavioral expression of
      pain does not indicate a lack of pain itself. These patients also demonstrated a
      reliance on folk beliefs and nondrug interventions. The most common reason cited
      for noncompliance with pharmacologic treatment was an inability to understand
      instructions. CLINICAL IMPLICATIONS: When providing care to Hispanic patients, it
      is imperative to be nonjudgmental, sensitive, and respectful. To improve
      compliance, the multidisciplinary cancer team should 1) incorporate the patients'
      folk healthcare practices and beliefs into the plan of care when possible; 2)
      involve family members and friends in the patient's care, identifying one key
      family contact; and 3) ensure that instructions for medications are available in
      Spanish and understood by the patient and care giver. When patients' overall
      beliefs and values are respected, compliance with pharmacological and other
      interventions may increase accordingly.

PMID- 9767347
TI  - Bulletin board

PMID- 9767345
TI  - Telephone prescreening enhancing a model for proactive healthcare practice.
AB  - PURPOSE: This article explicates the process of developing and implementing a
      contemporary, innovative program using the telephone as a tool for prescreening
      newly diagnosed cancer patients before their arrival at the cancer center. As
      another element of existing models of psychosocial care, this service lays the
      foundation for the efficient delivery of clinical social work services.
      DESCRIPTION OF PROGRAM: In the Surgical Oncology Clinic of the M.D. Anderson
      Cancer Center in Houston, Tex, 28 patients were contacted as part of a telephone
      prescreening model of a practice program from February 1, 1995 through March 31,
      1995. Using a structured telephone interview format, two clinic social workers
      contacted patients and provided information on social work services. Patients
      needing resource assistance were provided with community referrals. Using the
      information from the telephone call, a brief outpatient assessment was completed
      for each patient before his or her arrival at the clinic. During the initial
      clinic visit, each new patient was met by the social worker to conduct a
      qualitative interview and address specific treatment-related concerns. OUTCOME OF
      PROGRAM: The patients expressed their appreciation of the interest of the social
      work staff and their satisfaction with the information provided. In addition,
      obtaining patient information and identifying patient needs before the initial
      visit allowed social workers to use clinic time more efficiently. Because of
      restructuring, the Surgical Oncology Clinic was eliminated and use of the
      intervention suspended. Based on the encouraging results of the telephone
      prescreening model of care program, reinstating the program in the future would
      include expanding its hours of operation to reach individuals who are not at home
      during the hours of 8:00 am 25:00 pm and including language assistance to address
      the needs of the increasingly multicultural population. CLINICAL IMPLICATIONS:
      Telephone prescreening is one strategy for personalizing psychosocial assessment.
      In this era of outpatient day surgery and cost-controlled managed healthcare, the
      benefits of prescreening are empowerment for both patients and multidisciplinary
      team members. The future holds promise for telephone prescreening to become part
      of the collaborative clinical pathways model of the disease-site centers concept.

PMID- 9767346
TI  - Options in the treatment of chemotherapy-induced emesis.
AB  - PURPOSE: The incidence and duration of chemotherapy-induced emesis,
      pathophysiology of the emetic response, and antiemetic treatment of options are
      reviewed. OVERVIEW: Nausea and vomiting are among the most common and
      debilitating side effects of cancer chemotherapy. If not controlled, these side
      effects may interfere with the delivery of potentially life-saving treatment.
      Acute, delayed, and anticipatory nausea and vomiting may be prevented by
      appropriate antiemetic therapy. Drug selection is based on the emetogenicity of
      the patient's cancer treatment and potency of the antiemetic agent. Efficacy and
      safety of the antiemetic regimen are often improved by combining agents with
      different mechanisms of action. CLINICAL IMPLICATIONS: By preventing and
      controlling chemotherapy-induced emesis, clinicians may improve cancer patients'
      functional status and quality of life significantly. Improved tolerability may
      lead to greater patient acceptance of chemotherapy and prevent premature
      withdrawal from or cessation of treatment. Controlling chemotherapy-induced
      emesis also helps to decrease the direct and indirect costs of managing cancer.

PMID- 9767348
TI  - Quality of life in cancer patients: use of a revised Hospice Index.
AB  - PURPOSE: Improving or maintaining the quality of life for persons with cancer is
      a major goal of end-of-life care; however, to measure quality-of-life outcomes, a
      valid and reliable measure is needed. The purpose of this project was to report
      the psychometric properties of the revised Hospice Quality of Life Index (HQLI),
      including validity and reliability for hospice patients with cancer. DESCRIPTION:
      Data were collected from home care hospice patients with cancer (n = 255) and a
      group of apparently healthy adults in the community (n = 32). The revised HQLI is
      a 28-item self-report instrument that includes three subscales:
      Psychophysiological Well-being, Functional Well-being, and Social/Spiritual Well
      being. RESULTS: Evidence for validity was provided in three ways. First, factor
      analysis confirmed the three subscales (Psychophysiological, Functional, and
      Social/Spiritual Well-being). Second, a weak significant correlation was found
      between the Easterm Cooperative Oncology Group Performance Status Rating scores
      and HQLI scores (r = .26; P = .00). Third, the HQLI was able to discriminate
      between hospice patients with cancer and apparently healthy adults (lambda = .34;
      P = .00). In addition, the mean scores of these two groups were significantly
      different (t = 6.64; P = .00). However, only a minimal difference in scores was
      found on the Social/Spiritual Well-being subscale between the cancer and healthy
      groups. Reliability for the revised HQLI was high for both the total scale (alpha
      = .88) and the subscales (alpha =.82-.85). CLINICAL IMPLICATIONS: Emphasis has
      been placed recently on understanding quality of life from the patient's
      perspective. The development of a valid and reliable tool can guide care givers
      in providing meaningful quality-of-life care. The HQLI provides patients the
      opportunity to express beliefs about quality-of-life issues and to maintain
      direction over a critical aspect of their care. Of note from this study, the
      significant difference between groups in functional well-being and minimal
      difference in social/spiritual well-being suggest that patients are able to
      appraise their functional abilities realistically and still maintain their social
      network and spiritual beliefs. Indeed, it may be that patients give family
      relationships and spiritual beliefs greater focus during a terminal illness.

PMID- 9767350
TI  - Controversies in cancer care: hormone replacement therapy after breast cancer:
      how shall we do no harm?

PMID- 9767349
TI  - Missed cancer screening opportunities among older women: a review.
AB  - PURPOSE: The authors present an analysis of the literature and findings from a
      qualitative research study as a framework for discussion of potential strategies
      to increase utilization of breast and cervical cancer screening among older
      women. The qualitative findings are one component of a comprehensive two-part
      study investigating why providers miss the opportunity to screen older women for
      cancer. OVERVIEW: Qualitative analysis of in-depth interviews with experts in
      cancer control (academicians, clinicians, and cancer center administrators) and a
      survey of primary care providers revealed four emergent themes of patient,
      provider, office, and access barriers that contribute to underutilization of
      screening. Patient and provider barriers represent human factors or reasons why
      both groups may be reluctant to participate in screening. Office and access
      barriers exemplify systems factors that impede the screening process for both
      groups. Primary care providers may miss the opportunity to perform or recommend
      screening for underserved groups of older women because of their perceptions of
      these human and systems factors. CLINICAL IMPLICATIONS: In light of the critical
      importance of primary care providers' recommendations, health professionals and
      community leaders should collaborate in developing multifaceted programs to help
      providers feel more comfortable about promoting screening to their patients. Such
      comprehensive, coordinated initiatives, which adapt successfully proven
      strategies to community needs and resources, may be essential to increase
      utilization of screening among underserved groups of older American women.

PMID- 9767351
TI  - Resources for alternative and complementary cancer therapies.

PMID- 9767352
TI  - Capecitabine: A new oral fluoropyrimidine.

PMID- 9767353
TI  - Increasing awareness of the European Society for Clinical Investigation.

PMID- 9767354
TI  - Clinical implications of mutations in the hepatitis B virus genome.

PMID- 9767356
TI  - Haemodynamic effects of 8-day octreotide and prazosin administration in portal
      hypertensive rats.
AB  - BACKGROUND: Octreotide and prazosin are both effective portal hypotensive drugs
      in the control or prevention of variceal bleeding. The present study was
      undertaken to investigate the haemodynamic effects of octreotide and prazosin,
      alone or in combination, in portal hypertensive rats. METHODS: 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 12
      h-1), octreotide group (30 micrograms kg-1 12 h-1), prazosin group (0.4 mg kg-1
      12 h-1), and octreotide (30 micrograms kg-1 12 h-1) plus prazosin (0.4 mg kg-1 12
      h-1) group-with eight rats in each group. Prazosin or saline was administered by
      gavage, whereas octreotide was administered by subcutaneous injection. The drug
      was given on the day of ligation and continued for 8 consecutive days. Systemic
      as well as splanchnic haemodynamic parameters were measured thereafter. RESULTS:
      Portal vein-ligated rats exhibited typical hyperdynamic state compared with sham
      operated rats. The portal venous pressure, portal tributary blood flow and
      cardiac index were significantly reduced by treatment of octreotide, prazosin or
      octreotide plus prazosin in portal hypertensive rats. Hyperdynamic parameters of
      systemic, renal and portal territory vascular resistances, and renal as well as
      hepatic arterial blood flow were ameliorated by treatment of octreotide or
      octreotide plus prazosin in portal hypertensive rats. Overall, octreotide
      treatment exerted more beneficial haemodynamic effects than prazosin treatment.
      The combination of octreotide and prazosin exerted better haemodynamic effects in
      cardiac index but worse effects in systemic as well as portal territory vascular
      resistance than octreotide treatment alone.

PMID- 9767355
TI  - Carbohydrate-deficient transferrin is not a useful marker for the detection of
      chronic alcohol abuse.
AB  - BACKGROUND: The role of carbohydrate-deficient transferrin (CDT) as a reliable
      marker for the detection of chronic alcohol abuse has been discussed
      controversially. METHODS: Therefore, we investigated CDT in the sera from 405
      subjects with different alcohol intake. Besides healthy control subjects (n =
      42), inpatients and outpatients in a department of gastroenterology (n = 325) and
      patients admitted to a department of otorhinolaryngology (n = 38) were studied. A
      total of 213 patients suffered from various forms of liver diseases, and 89
      patients had liver transplantation. CDT values were determined by a double
      antibody radioimmunoassay. RESULTS: In the 241 alcohol-abstinent subjects, CDT
      levels ranged from 3 to 90 units L-1 (median = 12); the 92 moderate drinkers (20
      60 g of alcohol per day) showed values from 3 to 40 units L-1 (median = 12), and
      the 72 subjects with chronic alcohol abuse (> 60 g per day) revealed CDT levels
      from 3 to 100 units L-1 (median = 16). The diagnostic specificity for alcohol
      abuse was 86.8% for men (sensitivity 36.9%) and 95% for women (sensitivity 0%).
      CONCLUSION: Our data indicate that measurement of CDT does not reach clinical use
      in the detection of chronic alcohol abuse in an unselected population because of
      its insufficient specificity and sensitivity.

PMID- 9767357
TI  - Effects of omega-3 fatty acids and/or antioxidants on endothelial cell markers.
AB  - BACKGROUND: Increased expression of cell adhesion molecules and increased
      procoagulant activity of the vascular endothelium have been postulated to
      characterize dysfunctional endothelium. The cellular effects of n-3 fatty acids
      (n-3 FAs) and antioxidants are still not clarified. METHODS: In a randomized,
      factorial two-by-two design study, we have investigated 41 male smokers with
      hyperlipidaemia before and after 6 weeks of supplementation with either n-3 FAs
      (4.8 g daily) or placebo with the addition of antioxidants (150 mg of vitamin C,
      75 mg of vitamin E and 15 mg of beta-carotene daily) or placebo with regard to
      the effects on some endothelial cell markers: thrombomodulin (sTM), von
      Willebrand factor (vWF), tissue plasminogen activator antigen (tPAag) and soluble
      forms of the cell adhesion molecules E-selectin, P-selectin and vascular cell
      adhesion molecule 1 (VCAM-1). RESULTS: In the n-3 FA group, significant
      reductions in the plasma levels of vWF (P = 0.034) and sTM (P < 0.001) were
      demonstrated compared with placebo, whereas increased levels were found for E
      selectin (P = 0.001) and VCAM-1 (P = 0.010). In the antioxidant group, no
      differences in changes were noted for any of the variables. CONCLUSION: The
      reduction in the levels of sTM and vWF with n-3 FA supplementation could indicate
      an improvement with regard to the haemostatic markers of endothelial dysfunction,
      whereas the simultaneous increase in the soluble forms of E-selectin and VCAM-1
      may suggest an adverse effect on the inflammatory system. The antioxidants seem
      to be neutral in their effect on these endothelial cell markers in our study
      population of smokers. The interpretation of the soluble forms of these molecules
      are, however, still debatable.

PMID- 9767358
TI  - Cardiac natriuretic peptides for diagnosis and risk stratification in heart
      failure: influences of left ventricular dysfunction and coronary artery disease
      on cardiac hormonal activation.
AB  - BACKGROUND: Cardiac natriuretic peptides are activated in heart failure. However,
      their diagnostic and prognostic values have not been compared under the routine
      conditions of an outpatient practice. METHODS: We studied the diagnostic and
      prognostic value of plasma N- and C-terminal peptides of the atrial natriuretic
      factor prohormone (N-proANF and ANF respectively) and brain natriuretic peptide
      (BNP) to evaluate the severity of congestive heart failure (CHF) as reflected by
      the New York Heart Association (NYHA) classification and to predict its 2-year
      mortality. Peripheral plasma concentrations of the three natriuretic peptides
      were measured in 27 normal subjects (CTR), in 32 patients with coronary artery
      disease (CAD) and normal left ventricular ejection fraction and in 101 patients
      with chronic CHF in functional classes I and II (n = 61) or III and IV (n = 40).
      RESULTS: Plasma concentrations of the three peptides increased in the presence of
      CHF in relation to its severity (P < 0.01). BNP was unable to distinguish CTR
      from CAD, just as ANF could not differentiate CAD from CHF I-II; only N-proANF
      displayed a significant and continuous increase from CTR to CAD, CHF I-II and III
      IV. Receiver-operating characteristic curves showed better evaluation of the
      degree of CHF by BNP than by ANF or ejection fraction (P < 0.05). Assessment of
      the 2-year prognosis revealed that N-proANF and BNP were the best independent
      predictors of outcome after the NYHA classification. These peptides identify a
      very high-mortality group. CONCLUSION: Plasma N-proANF and BNP concentrations are
      good indicators of the severity and prognosis of CHF in an outpatient practice.
      CAD does not stimulate BNP as long as ventricular dysfunction is not present,
      although increased N-proANF levels in this setting suggest an early humoral
      activation.

PMID- 9767359
TI  - Cardiovascular risk factors associated with clinically isolated and diffuse
      atherosclerosis in Spanish patients with coronary artery disease.
AB  - BACKGROUND: Patients with coronary artery disease (CAD) associated with
      peripheral (PAD) or cerebrovascular disease (CVD), a condition called diffuse
      atherosclerosis, have a higher risk of death than patients with isolated CAD. The
      prevalence of diffuse atherosclerosis and the atherogenic risk factors associated
      with this condition in our geographic area have not been described previously.
      METHODS: A cohort of 2597 patients (62 +/- 10.8 years, 665 women) consecutively
      admitted at Bellvitge Hospital because of acute coronary syndromes were studied.
      CAD patients were divided in two groups with diffuse and located atherosclerosis
      according to whether they had or they had not an associated PAD or CVD. Baseline
      history, physical data and lipid profile were recorded in each patient according
      to a standardized questionnaire. RESULTS: A total of 370 patients (14.2%) had
      diffuse atherosclerosis. Among them, there were more men and women older than 55
      years than among those with isolated CAD. Patients with diffuse atherosclerosis
      were more frequently hypertensive, diabetic and former smokers than those with
      isolated CAD (60.5% vs. 49.4%, P < 0.01; 37.4% vs. 24.5%, P < 0.01; and 47% vs.
      35.7%, P < 0.01, respectively). There were no significant differences in the mean
      values of total cholesterol (TC), low-density cholesterol (LDL-C), high-density
      cholesterol (HDL-C) and triglycerides between both groups of patients, but
      patients with diffuse atherosclerosis had a lower HDL-C/TC ratio, with borderline
      statistical significance (0.18 +/- 0.06 vs. 0.19 +/- 0.06, P = 0.06). Using
      multiple logistic regression analysis, the variables associated with diffuse
      atherosclerosis in men were age greater than 55 years (OR 1.97, CI 1.33-2.93),
      hypertension (OR 1.50, CI 1.14-2.20), diabetes (OR 1.78, CI 1.20-2.70), smoking
      (former smokers) (OR 2.09, CI 1.36-3.24) and HDL-C/TC < 0.20 (OR 1.60, CI 1.18
      2.17); and in women hypertension (OR 3.43, CI 1.48-7.94) and diabetes (OR 2.58,
      CI 1.55-4.80). CONCLUSIONS: Clinically overt diffuse atherosclerosis is a
      relatively common disease. Older patients and those with hypertension, diabetes
      or low HDL-C/TC ratio are more likely to have diffuse atherosclerosis than those
      without these conditions.

PMID- 9767361
TI  - Plasma and platelet ascorbate pools and lipid peroxidation in insulin-dependent
      diabetes mellitus.
AB  - BACKGROUND: As diabetes mellitus represents a situation in which production of
      peroxides is increased, the aim of this study was to investigate the relationship
      between plasma and platelet levels of ascorbic acid (AA)/dehydroascorbic acid
      (DHA) and those of malonyldialdehyde (MDA), an indirect marker of lipoperoxides,
      both assayed using high-performance liquid chromatography (HPLC), in 59 patients
      with insulin-dependent diabetes mellitus (IDDM) compared with 51 healthy control
      subjects matched for sex, age, smoking habits, as well as for dietary intake of
      energy, alcohol and vitamin C. RESULTS: Mean plasma and platelet MDA were
      significantly higher in the patients affected with IDDM than in control subjects.
      Moreover, the diabetic group was characterized by a huge decrease in plasma AA
      [8.45 +/- 5.5 mumol L-1 (SD) vs. 33.4 +/- 7.6 mumol L-1, P = 0.0001], mirrored by
      a significant increase in plasma DHA (11.9 +/- 3.9 mumol L-1 vs. 3.9 +/- 2.5
      mumol L-1, P = 0.0001). No detectable DHA was observed in the platelets from both
      diabetic and control subjects, whereas AA was significantly increased in
      platelets from diabetic patients compared with control subjects (42.6 +/- 7.4 vs.
      34.8 +/- 5.1 nmol 10(-9) platelets, P = 0.0001). Platelet AA in the diabetic
      group was significantly inversely correlated with glycated haemoglobin (r = 
      0.34; P = 0.04) and directly with plasma AA (r = 0.39; P = 0.02), the sum of
      plasma AA + DHA (r = 0.44; P = 0.009) and with platelet MDA (r = 0.38; P = 0.02).
      CONCLUSION: (a) The ratio plasma AA/DHA is significantly lowered in IDDM in
      association with an increase in MDA levels; (b) only AA is detected in platelets,
      being augmented in the diabetic group; (c) plasma ascorbate depletion does not
      reflect platelet levels of AA; and, finally, (d) metabolic control, as well as
      intracellular lipoperoxides, modulates platelet AA in IDDM.

PMID- 9767360
TI  - Acute and chronic exposure of rat intestinal mucosa to dextran promotes SGLTI
      mediated glucose transport.
AB  - BACKGROUND: The intestinal handling of dextran, an alpha-1,6-linked glucose
      polymer, is poor compared with starch, and some ingested dextran might therefore
      reach the lower small intestine. As luminal sugar up-regulates SGLT1 (sodium
      dependent glucose transporter) locally, we report the effects of a dextran
      enriched diet on jejunal and ileal brush border membrane (BBM) glucose uptake.
      METHODS: Rats were maintained on a diet containing 65% maltodextrin or 32.5%
      maltodextrin + 32.5% dextran (10 kD or 40 kD) for 8-10 days, and the kinetics of
      phlorizin-sensitive [3H]-glucose uptake by purified BBM vesicles was determined.
      RESULTS: Ingestion of 40-kD but not 10-kD dextran increased Vmax for jejunal and
      ileal glucose uptake (+64.3% and +61.8% respectively, both P < 0.02). The
      transport response to 40-kD dextran was in keeping with lower levels of expired
      H2 at the end of the feeding period. High-performance liquid chromatography
      (HPLC) analysis of luminal contents indicated extensive hydrolysis of ingested
      dextran. Finally, 3-h jejunal exposure to 40-kD dextran in vivo increased the
      Vmax for glucose uptake by jejunal BBM. CONCLUSION: It is likely that increased
      SGLT1-mediated glucose uptake after short or longer term mucosal exposure to
      dextran results from luminal dextran per se or a hydrolysis product. The clinical
      implications of this up-regulation are discussed.

PMID- 9767362
TI  - Transdermal nicotine inhibits interleukin 2 synthesis by mononuclear cells
      derived from healthy volunteers.
AB  - BACKGROUND: Smoking has either a beneficial or harmful effect on the course and
      recurrence of ulcerative colitis (UC) and Crohn's disease respectively.
      Transdermal application of nicotine had similar effects in UC and therefore was
      considered to be an effective basic drug that could be further developed in the
      search for new compounds in the treatment of acute exacerbations of
      corticosteroid-resistant UC. To clarify the hypothesis that nicotine exerts its
      anti-inflammatory effect in UC through selective inhibition of T-cell-derived
      cytokine synthesis, we studied in vivo effects of nicotine on cytokine production
      by human non-adherent mononuclear cells isolated from peripheral blood in a
      randomized, double-blind, placebo-controlled trial. METHODS: Healthy non-smoking
      volunteers applied for 2 weeks of nicotine patches (n = 12) with incremental
      doses of nicotine during the first week to achieve a maintenance dose of 15 mg
      per day, or placebo (n = 12). Blood was obtained before treatment and 1, 2, 3 and
      6 weeks after the start of treatment. Cells were cultured in the absence or
      presence of phytohaemagglutinin for 48 h, and total amounts of interleukin 2 (IL
      2), IL-4, IL-10, IL-13, interferon gamma (IFN-gamma) and tumour necrosis factor
      alpha (TNF-alpha) were measured. RESULTS: Transdermal nicotine caused a
      significant inhibition of IL-2 after 2 weeks' treatment compared with the placebo
      group. In addition, a diminished production of IL-10 and TNF-alpha in comparison
      with day 0 was observed. CONCLUSION: The beneficial effect of transdermal
      nicotine in ulcerative colitis may be mediated by a selective inhibition of the
      IL-2 production by mucosal mononuclear cells, which could result in diminished
      cell proliferation and consequently a reduction in the inflammatory process.

PMID- 9767363
TI  - Time course of immunological markers in patients with the systemic inflammatory
      response syndrome: evaluation of sCD14, sVCAM-1, sELAM-1, MIP-1 alpha and TGF
      beta 2.
AB  - BACKGROUND: The systemic inflammatory response syndrome (SIRS) is viewed as a
      system-wide inflammatory response. Up until now, no parameter has been available
      for predicting the development of septic shock. In the present study, we
      evaluated the usefulness of serum levels of CD14, vascular cells adhesion
      molecule-1 (VCAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1),
      macrophage inflammatory protein (MIP) 1 alpha and transforming growth factor beta
      2 (TGF-beta 2) as early markers of outcome in patients with SIRS. METHODS: A
      group of 28 SIRS patients (13 survivors/15 non-survivors) was compared with a
      healthy control group and with patients with local inflammation. Blood samples
      were analysed on days 0, 4 and 7. Proinflammatory parameters such as sCD14, sVCAM
      1, sELAM-1, MIP-1 alpha and anti-inflammatory parameters such as TGF-beta 2 were
      determined using enzyme-linked immunosorbent assay (ELISA). RESULTS: At the
      beginning, all evaluated proinflammatory immunological parameters with the
      exception of sVCAM-1 were significantly increased in patients with SIRS compared
      with the healthy control group. However, no significant difference could be
      observed for all immunological parameters comparing survivors and non-survivors,
      with the exception of interleukin (IL) 6 at day 7. CONCLUSION: All evaluated
      proinflammatory parameters were increased in patients with SIRS during the course
      of the disease. However, the parameters have no correlation with outcome and
      prognosis of SIRS patients.

PMID- 9767364
TI  - Cytokine regulation of the acute-phase protein levels in multiple myeloma.
AB  - BACKGROUND: Interleukin (IL) 6 has an important role in the regulation of acute
      phase proteins (APPs) during an acute-phase response. We studied IL-6 and other
      cytokines to determine if they regulate serum APP levels in the same way under
      the condition of the aberrant, long-lasting 'acute-phase response' that occurs in
      patients with chronic inflammation and cancer. METHODS: Serum levels of nine
      positive APPs [CRP, SAA, C1-INH, Bf, C5, C8, C9, alpha 1-acidic glycoprotein
      (AGP) and haptoglobin] and two negative APPs [transferrin and alpha 2-HS
      glycoprotein (AHSG)] were measured using immunochemical methods in 59 multiple
      myeloma patients and in 72 healthy control subjects. Serum IL-6 and tumour
      necrosis factor (TNF) alpha levels were determined by bioassays. RESULTS: IL-6
      was negatively correlated with five out of nine (C1-INH, C8, C9, AGP and
      haptoglobin) positive APPs but positively correlated with C-reactive protein
      (CRP). When patients with high and low IL-6 serum concentration were compared,
      CRP levels were higher, AGP and haptoglobin levels were lower in the high- than
      in the low-L-6 group, whereas no significant difference between the two groups
      was found in levels of the other positive and negative APPs. TNF-alpha levels
      were negatively correlated with transferrin and AHSG levels. No difference in the
      levels of positive APPs was observed between patients with low and high TNF-alpha
      serum concentration. By contrast, levels of both transferrin and AHSG were
      significantly lower in the high- than in the low-TNF-alpha group. CONCLUSIONS:
      These findings indicate that, except for regulation of the negative APPs by TNF
      alpha, the mechanism of APP regulation is different under the conditions of the
      short-term and the chronic, long-lasting 'acute-phase reaction'.

PMID- 9767366
TI  - Kjeld Winkler, former Editor-in-Chief, EJCI.

PMID- 9767367
TI  - Relative hyperoxaluria, crystalluria and haematuria after megadose ingestion of
      vitamin C.
AB  - BACKGROUND: Long-term or high-dosage consumption of vitamin C may play a role in
      calcium oxalate kidney stone formation. The present study was undertaken to
      determine the biochemical and physicochemical risk factors in a male subject who
      developed haematuria and calcium oxalate crystalluria after ingestion of large
      doses of ascorbic acid for 8 consecutive days. METHODS: Twenty-four-hour urine
      samples were collected before and during the ascorbic acid ingestion period as
      well as after the detection of haematuria. A special procedure was implemented
      for urine collections to allow for oxalate, ascorbate and other urinalysis.
      Oxalate was determined in the presence of EDTA to prevent in vitro conversion to
      ascorbic acid, whereas ascorbate itself was determined by manual titration in a
      redox method using the dye dichlorophenolindophenol. Urinalysis data were used to
      compute calcium oxalate relative supersaturations and Tiselius risk indices,
      whereas scanning electron microscopy was used to examine urinary deposits.
      RESULTS: Oxalate excretion increased by about 350% during ascorbate ingestion
      before haematuria. Ascorbate concentrations also increased dramatically but
      appeared to reach a plateau maximum. Increasing calcium excretion was accompanied
      by decreasing potassium and phosphate values. The calcium oxalate relative
      supersaturation and Tiselius risk index increased during vitamin C ingestion and
      large aggregates of calcium oxalate dihydrate crystals were observed by scanning
      electron microscopy immediately after the detection of haematuria. CONCLUSION:
      High percentage metabolic conversion of ascorbate to oxalate in this subject
      caused relative hyperoxaluria and crystalluria, the latter manifesting itself as
      haematuria. Clinicians need to be alerted to the potential dangers of large dose
      ingestion of vitamin C in some individuals.

PMID- 9767365
TI  - Investigation into thiol conjugation of transthyretin in hereditary transthyretin
      amyloidosis.
AB  - BACKGROUND: For all forms of amyloidosis, the amyloid-generating mechanism is
      unknown. Familial amyloidotic polyneuropathy type I is caused by a variant
      transthyretin (TTR Met-30). As electrospray ionization mass spectrometry (ESI-MS)
      discloses both thiol-conjugated and -unconjugated forms of wild-type and variant
      TTR, we wanted to investigate the relationship between TTR conjugation and
      clinically overt amyloid disease. METHODS: Plasma from 35 individuals (12
      symptomatic TTR Met-30 carriers, nine asymptomatic and 14 healthy control
      subjects) were analysed using ESI-MS. RESULTS: The total TTR concentration was
      significantly lower in symptomatic TTR Met-30 carriers than in control subjects.
      An increased percentage of conjugated TTR Met-30 was found in symptomatic
      carriers compared with asymptomatic, whereas the percentage conjugated wild-type
      TTR was similar for control subjects, asymptomatic and symptomatic TTR Met-30
      carriers. CONCLUSION: The finding of a decreased ratio of unconjugated to
      conjugated TTR Met-30 in plasma samples from symptomatic TTR Met-30 carriers
      indicates that thiol conjugation of TTR could be involved in amyloid formation.

PMID- 9767368
TI  - Effects of digoxin and digitoxin on circadian blood pressure profile in healthy
      volunteers.
AB  - BACKGROUND: The aim of the study was to investigate the potential effects of
      chronic digoxin or digitoxin treatment or circadian blood pressure profile in
      normotensive subjects. METHODS: In two randomized double-blind, placebo
      controlled cross-over protocols, 22 healthy normotensive subjects were enrolled,
      12 subjects in either study. After adequate loading doses, digoxin 0.25 mg twice
      daily or digitoxin 0.1 mg daily was given for a total of 10 days. Automatic 24-h
      ambulatory blood pressure measurements were carried out at days 4 and 10 of
      either glycoside or placebo. RESULTS: Digoxin treatment significantly decreased
      heart rate (HR) and diastolic blood pressure (DBP) during the overnight sleeping
      phase of day 10 compared with placebo (HR, 4 beats min-1; DBP, 8 mmHg; P < 0.05).
      Digitoxin treatment significantly decreased heart rate and diastolic blood
      pressure during the overnight sleeping phase of day 4 (HR, 8 beats min-1; DBP, 7
      mmHg) and day 10 (HR, 7 beats min-1; DBP, 5 mmHg) compared with placebo (P <
      0.05). Neither digoxin nor digitoxin significantly affected systolic blood
      pressure. CONCLUSIONS: Both digoxin and digitoxin, within therapeutic steady
      state plasma concentrations, reduced diastolic blood pressure and heart rate
      during overnight sleep, presumably because of increased parasympathetic activity
      or decreased sympathetic activity.

PMID- 9767369
TI  - Mutations in the carboxy terminus of the beta and gamma subunits of the
      epithelial sodium channel are not present in patients with hypertensive crisis.
AB  - BACKGROUND: The pathophysiology of hypertensive crises is poorly understood. To
      date, no information is available about genetic determinants underlying the
      individual risk for development of hypertensive urgencies or emergencies.
      Recently, mutations in the beta subunit (h beta ENaC) and the gamma subunit (h
      gamma ENaC) of the human epithelial sodium channel (hENaC) have been shown to
      result in excessive elevation of blood pressure in patients with Liddle's
      syndrome. METHODS: Using polymerase chain reaction and direct sequencing of
      amplification products we have screened 90 consecutive out-patients with
      hypertensive urgency or hypertensive emergency for the presence of mutations in
      the carboxy terminus of these genes. Furthermore, serum potassium concentrations
      were determined in all 90 patients, and serum aldosterone levels and plasma renin
      activity were measured in a subset of 34 patients. RESULTS: Among 71 patients
      with hypertensive urgency (78.9%) and 19 patients with hypertensive emergency
      (21.1%) not one individual showed a mutation in genomic DNA extending from codon
      532 to codon 637 of h beta ENaC and from codon 525 to codon 651 of h gamma ENaC.
      Twelve of 90 patients showed mild hypokalaemia (13.3%), 16 of 34 patients had a
      plasma renin activity below the lower normal range (47.1%) and one of 34 patients
      had a low serum aldosterone concentration (2.9%). CONCLUSIONS: The present study
      clearly demonstrates the absence of mutations in the carboxy terminus of the h
      beta ENaC and h gamma ENaC gene of hENaC in an Austrian cohort of 90 patients
      suffering from hypertensive crisis.

PMID- 9767370
TI  - New type of the internalization-defective low-density lipoprotein receptor owing
      to two-nucleotide deletion (2199delCA or 2201delCA) in Japanese patients with
      familial hypercholesterolaemia.
AB  - BACKGROUND: In mutations of the low-density lipoprotein (LDL) receptor gene, the
      defect of internalization is caused by a mutation in the cytoplasmic domain of
      the receptor linked with exons 17 and 18, and the O-linked sugar domain linked
      with exon 15 has been speculated not to affect the function of the receptor.
      Here, we describe a novel mutation of the O-linked sugar domain of the LDL
      receptor gene, designated familial hypercholesterolaemia (FH)-Mishima with
      Japanese pedigree, which resembles but still differs from classical defective
      internalization cases. METHODS: LDL metabolism was examined in cultured skin
      fibroblasts from patients. Immunoprecipitation and immunohistochemical techniques
      were applied for the detection of the receptor protein size and distribution.
      Screening of the mutant exon(s) of the LDL receptor gene was performed using the
      polymerase chain reaction-single-strand conformation polymorphism technique (PCR
      SSCP), and sequencing of the mutated alleles was carried out using the dideoxy
      chain termination method. RESULTS: LDL-binding activity at 4 degrees C in skin
      fibroblasts from patients was similar to normal, but that at 37 degrees C with
      the ligand decreased time dependently and was lost at 6 h, resulting in the
      defect of internalization and degradation of LDL. The receptor protein on the
      cell surface was detected at 4 degrees C by IgG-C7, an anti-LDL receptor
      antibody, but was not detected after incubation with LDL at 37 degrees C. The
      size of the receptor was 112 kD as determined by immunoprecipitation analysis. A
      deletion of two nucleotides in exon 15 was detected in the DNA sequence of the
      LDL receptor gene. The deletion results in a shift of the reading frame after Thr
      713 of the mutant and makes a stop codon at amino acid 759. CONCLUSION: Deletion
      of the two nucleotides caused novel amino acid sequences after the O-linked sugar
      domain, which has the ability of sorting on the cell membrane at 4 degrees C, but
      not at 37 degrees C in vivo, resulting in the complete cessation of activity of
      the LDL receptor.

PMID- 9767371
TI  - Varying very low-density lipoprotein secretion of rat hepatocytes by altering
      cellular levels of calcium and the activity of protein kinase C.
AB  - BACKGROUND: Calcium antagonists lower plasma levels of lipoproteins and suppress
      hepatic very low-density lipoprotein (VLDL) secretion. Similar effects have been
      observed with the calcium ionophore A23187. We studied further the effect of
      calcium on VLDL metabolism. METHODS: Hepatocytes from male Wistar rats were
      isolated and cultured in the presence or absence of calcium-mobilizing hormones,
      or compounds that either stimulate or inhibit the activity of protein kinase C.
      Secreted VLDL (d < 1.006 g mL-1) was isolated by centrifugation (145,000 x g),
      and lipids and apolipoprotein B were analysed. RESULTS: VLDL secretion reached
      maximum in hepatocytes cultured in medium containing calcium 0.8-2.4 mmolL-1.
      Depleting the cells of calcium by incubating in calcium-free medium or by
      treating the cells with the Ca(2+)-ATPase inhibitor thapsigargin (5 x 10-7 molL
      1) suppressed lipid secretion to less than 15% of control, and this was
      accompanied by an increase in cellular levels of triacylglycerol. Calcium loading
      (medium calcium > 2.4 mmolL-1) suppressed both lipoprotein secretion and cellular
      levels of lipids, suggesting a reduced overall rate of lipid synthesis. At an
      extracellular calcium concentration of 0.8 mmolL-1, angiotensin II, vasopressin,
      endothelin-1 (10(-7) molL-1) or phenylephrine (10(-4) molL-1) suppressed VLDL
      secretion (maximum to 37% of control), and elevated medium calcium attenuated
      this effect. The protein kinase C inhibitor chelerythrine (5 x 10(-5) molL-1) and
      the protein kinase C activator phorbol 12-myristate 13-acetate (PMA) (10(-6) molL
      1), suppressed VLDL secretion to 18% and 60% of control, respectively, whereas
      the protein kinase C-inactive 4 alpha-PMA was without an effect. No effect on
      ketogenesis was observed by these compounds, indicating that suppressed lipid
      secretion was not due to an enhanced oxidation of lipids. CONCLUSIONS: Hepatic
      VLDL secretion can be related to changes in hepatocyte levels of calcium and the
      activity of protein kinase C.

PMID- 9767372
TI  - Plasma acylation stimulating protein (ASP) as a predictor of impaired cellular
      biological response to ASP in patients with hyperapoB.
AB  - BACKGROUND: The objective of this study was to examine specific membrane binding
      of [125I]-acylation stimulating protein (ASP) in cultured human skin fibroblasts
      obtained from normal subjects and patients with hyperapoB. ASP is a small basic
      protein isolated from human plasma that stimulates triglyceride synthesis (TGS)
      and glucose transport (GT) in human skin fibroblasts and adipocytes. DESIGN: In
      the present study, three groups were studied: normal (NASP-NB) subjects,
      hyperapoB subjects with normal plasma ASP (NASP-HB) and hyperapoB subjects with
      high plasma ASP (HASP-HB). RESULTS: ASP-induced TGS in fibroblasts from HASP-HB
      subjects was significantly less than in the two control groups with normal plasma
      ASP (NASP-NB and NASP-HB). Similarly, ASP stimulation of GT was less in HASP-HB
      fibroblasts than in the NASP-HB fibroblasts or the NASP-NB subjects. Insulin
      induced TGS was similar in all three groups as was insulin-stimulated GT. As
      well, protein kinase C-mediated stimulation was equivalent among the three groups
      both for GT and for TGS. There was no significant difference in the binding
      affinity (Kd) of [125I]-ASP to intact cells in any group. By contrast, binding of
      [125I]-ASP revealed a significantly lower Bmax of the HASP-HB cell lines than the
      NASP-NB cells and the NASP-HB cells. CONCLUSION: A decrease in the ASP cell
      surface receptor concentration is responsible for decreased ASP stimulation of
      TGS, and GT and may contribute to the inefficient postprandial triglyceride (TG)
      clearance in HASP-HB subjects.

PMID- 9767373
TI  - Mutations in the low-density lipoprotein receptor gene in Swedish familial
      hypercholesterolaemia patients: clinical expression and treatment response.
AB  - BACKGROUND: Familial hypercholesterolaemia, an autosomal co-dominant disorder
      caused by defects in the low-density lipoprotein receptor gene, is strongly
      associated with premature development of cardiovascular disease. METHODS: In this
      study, we have applied a gene screening method in a population of familial
      hypercholesterolaemia patients in order to describe the genetic background of the
      disease in southern Sweden. These patients were studied with the aim of relating
      the presence of the different mutations to the clinical expression of the disease
      and to the response to pharmacological treatment. RESULTS: In 16 out of 21
      patients, potentially disease-causing low-density lipoprotein receptor gene
      defects were found, including five not previously described alterations (C240-
      >F, C122-->stop, C356-->Y, 785insG, 165delG). No defects in apolipoprotein B were
      found. One group of patients (n = 4) carried the mutation C122-->stop and another
      group of patients (n = 4) a mutation causing the substitution W66-->G. Patients
      in the two genotype subgroups were very similar with respect to lipid levels
      before treatment. CONCLUSION: A tendency towards differential susceptibility to
      treatment with statins was observed for the patient groups, encouraging further
      comparative studies of heterozygous FH patients.

PMID- 9767374
TI  - Monitoring of extracellular matrix metabolism and cross-linking in tissue, serum
      and urine of patients with chromoblastomycosis, a chronic skin fibrosis.
AB  - BACKGROUND: Chromoblastomycosis is a fungal disease leading to a granulomatous
      reaction associated with dermal fibrosis. METHODS: In an attempt to elucidate the
      mechanisms leading to improvement in the cutaneous lesions after treatment with
      terbinafine, a new antifungal drug, we analysed collagen content and cross
      linking before and at the end of the treatment. The turnover of extracellular
      matrix was monitored for 1 year by following up serum and urinary metabolites.
      RESULTS: The serum levels of type III collagen and its N-terminal propeptide were
      correlated with the lesion size (P < 0.035) after 4 and 12 months of treatment
      respectively. After 4 months of treatment, urinary pyridinoline was higher (P =
      0.04) in patients whose lesion size was reduced by more than 50% and serum
      hyaluronan was lower in patients who had lesions active for less than 5 years (P
      < 0.05). The treatment increased pyridinoline and pentosidine cross-links in the
      lesions but significantly reduced the collagen content (P = 0.05). CONCLUSION:
      This is the first demonstration that, in addition to its fungicidal activity,
      terbinafine acts in vivo as an antifibrotic drug.

PMID- 9767375
TI  - Direct evidence for an increase in thrombopoiesis after liver transplantation.
AB  - BACKGROUND: In advanced liver cirrhosis, thrombocytopenia results from
      'hypersplenism' due to increased platelet sequestration and platelet 'pooling' in
      the enlarged spleen and/or from reduced platelet production in the bone marrow.
      We sought to differentiate between these two mechanisms by studying
      thrombopoiesis before and after orthotopic liver transplantation by the
      determination of reticulated platelets, direct indicators for the thrombopoietic
      activity in the bone marrow. METHODS: Reticulated platelets, peripheral platelet
      counts, mean platelet volumes and platelet-reactive antibodies were determined in
      15 patients suffering from advanced liver cirrhosis before and during an
      observation period of 14 days after orthotopic liver transplantation (OLT).
      Thrombopoietin levels of ten patients were determined before transplantation and
      consecutively for 14 days after surgery. RESULTS: All patients except one were
      thrombocytopenic before transplantation (median count 94 x 10(9) L-1, range 69
      114 x 10(9) L-1). Although levels of reticulated platelets rose 2 days after
      surgery from baseline values of 1.0% (range 0.2-1.6%) to peak values of 4.6%
      (range 1.7-17.9%, P < 0.05) on day 6, platelet counts declined during the first 5
      days after transplantation. When peripheral platelet counts increased to the
      normal range (median day 11, range day 8-33), reticulated platelets were again at
      pretransplant levels. Thrombopoietin levels before OLT were within the normal
      range (< 85 pg mL-1). On day 5 post surgery, a maximum increase of 5.8-fold
      (range 2.2- to 28-fold) over baseline values was observed. Mean platelet volume
      did not show any significant deviation from the baseline values and platelet
      antibodies could not be detected during the observation period. CONCLUSION: Our
      findings provide direct evidence for an increase in de novo platelet production
      after orthotopic liver transplantation. As the elevation of reticulated platelets
      precedes platelet recovery, it could serve as an early indicator to predict
      thrombopoiesis as a result of reconstituted liver function.

PMID- 9767376
TI  - Peroxynitrite generation might explain elevated glutamate and aspartate levels in
      multiple sclerosis cerebrospinal fluid.

PMID- 9767377
TI  - Effect of air pollutants on the pulmonary surfactant system.
AB  - Air pollutants have been recognized to influence the structure and function of
      the surfactant system. Agents that have received the most attention include
      ozone, nitrogen dioxide, hyperoxia, diesel exhaust, tobacco smoke, silica and
      fibrous materials such as asbestos. The deleterious effects of air pollutants on
      the surfactant system depend on the size of the agent, on its solubility in
      aqueous solutions and chemical reactivity and on its concentration and the
      duration of exposure. Hereby the following general rules apply: the smaller the
      agent's size and the less water soluble the pollutant is, the greater the
      tendency to reach the alveoli during breathing. In addition, the reactivity also
      determines the depth of penetration into alveoli. Compounds with high reactivity
      such as O3, which also fulfil the earlier rules, will react with the upper
      respiratory tract compared with compounds with slightly reduced reactivity, such
      as NO2, which will penetrate the alveoli. The common consequence of exposure to
      air pollutants is an accumulation of surfactant phospholipids and surfactant
      specific proteins in the bronchoalveolar lavage fluid. These components also are
      structurally altered, mainly by oxidant gases, resulting in impairment of their
      biological activity. Thus, for surfactant phospholipids, there is impaired
      adsorption to the air-liquid interface due to oxidation of their fatty acids.
      Also, surfactant protein A, regarded as a modulator of the surfactant system,
      shows impaired functions after exposure to oxidants. It is likely that in
      addition to the effects described in this review not all effects are known
      because the molecular effects of several key components (e.g. SP-B and C) have
      not been well studied.

PMID- 9767378
TI  - The association of type II pneumocytes and endothelial permeability with the
      pulmonary custocyte system in experimental acute pancreatitis.
AB  - BACKGROUND: Pancreatitis-associated pulmonary injury is still associated with
      substantial mortality, especially when seen as a part of the multiple organ
      dysfunction syndrome. METHODS: The present study aimed at evaluating alterations
      in type II pneumocytes and the potential relationship with the development of
      pulmonary injury after acute haemorrhagic pancreatitis induced by an intraductal
      infusion of 5% sodium taurodeoxycholate in the rat. RESULTS: The results
      demonstrated that definite alterations in type II pneumocytes were noted 12 and
      24 h after induction of pancreatitis, characterized by an increase in the number
      of vocalized lamellae, the exposed area of type II pneumocytes to alveolar
      airspace, cellular separation and apoptosis without alterations in cellular
      membrane integrity. Dysfunction of the pulmonary endothelial barrier was
      evidenced by an increase in pulmonary albumin flux and the leakage index as well
      as the migration of lanthanum probes from capillaries to interstitial tissues.
      The levels of tumour necrosis factor (TNF) in bronchoalveolar lavage fluid
      significantly increased during the initial phase (3 and 6 h) after pancreatitis.
      The phagocytic activity of the pulmonary custocyte system increased 3 and 12 h
      after induction of pancreatitis. CONCLUSION: Thus, pulmonary endothelial barrier
      dysfunction, an activated custocyte system, and initial release of TNF seems to
      be involved in the pathogenesis of pancreatitis-associated type II pneumocyte
      compromise.

PMID- 9767379
TI  - The expression of the glial glutamate transporter protein EAAT2 in motor neuron
      disease: an immunohistochemical study.
AB  - Emerging evidence suggests that a disturbance of the glutamate neurotransmitter
      system may be a contributory factor to motor neuron injury in motor neuron
      disease. Previous autoradiographic and immunoblotting studies have suggested that
      there may be reduced expression of glutamate transporter proteins in
      pathologically affected areas of the CNS in motor neuron disease. This study
      further explores the possible alteration in expression of the excitatory amino
      acid transporter protein EAAT2 in MND, by examining the protein expression in
      situ, in frozen sections, using immunohistochemistry. The aim of the study was to
      compare the distribution and density of EAAT2 in the motor cortex and spinal cord
      of MND cases (n = 16) compared with neurologically normal controls (n = 12),
      matched for relevant parameters. A novel, previously characterized, monoclonal
      antibody to EAAT2 was employed. EAAT2 immunoreactivity in motor neuron disease
      and control cases was compared using relative optical density measurements
      generated by computerized image analysis. In the motor cortex, EAAT2
      immunoreactivity was laminated comprising a superficial intense band
      (corresponding to layers 1 and 2); a paler middle band (layer 3 and part of 5)
      and a more intense deep layer (layers 5 and 6). In the spinal cord, the ventral
      horn showed strong immunoreactivity with dense perisomatic staining around motor
      neuron cell bodies, the substantia gelatinosa showed moderate diffuse staining
      and the intermediate spinal laminae showed weak staining. This general pattern of
      immunoreactivity was preserved in the motor neuron disease cases. However, in the
      motor neuron disease cases compared with controls, the optical density values for
      EAAT2 immunoreactivity were significantly reduced in all grey matter regions of
      the lumbar spinal cord (P < 0.001) and were increased in the middle laminae of
      the motor cortex (P < 0.05). This study indicates that glutamate transporter
      pathology in motor neuron disease may be a more complex phenomenon than
      previously recognized.

PMID- 9767380
TI  - Human FGF-1 gene delivery protects against quinolinate-induced striatal and
      hippocampal injury in neonatal rats.
AB  - Fibroblast growth factors (FGFs) are cell mitogens and differentiating factors
      with neuroprotective properties in the CNS. We have already shown that
      endothelial cells genetically engineered to secrete human FGF-1 (RBEZ-FGF)
      survive implantation to neonatal rat brain (Johnston et al. (1996) J. Neurochem.
      67, 1643-1652]. In this study, the effects of cell-based FGF-1 gene delivery on
      quinolinate-induced neurotoxicity in the developing rat brain were examined.
      Control endothelial cells (RBE4), and RBEZ-FGF cells were implanted into right
      striatum at post-natal day (PND) 7. On PND 10, quinolinate (150 nmol), an
      endogenous N-methyl-d-aspartate (NMDA) receptor agonist, or vehicle alone was
      injected into striatum ipsilateral to cell implantation. Injury was quantified in
      coronal sections obtained from PND 17 animals by comparing striatal and
      hippocampal volumes ipsilateral and contralateral to the site of quinolinate
      injection. Human FGF-1 specific transgene expression in vivo was shown by
      Northern blot and RT-PCR up to 14 days after cell implantation in control
      animals, and up to 4 days after quinolinate exposure. Quinolinate reduced the
      size of ipsilateral striatum by 37% and hippocampus by 38% in animals
      preimplanted with control endothelial cells. In contrast, quinolinate reduced the
      size of striatum by only 14% and had no effect on hippocampal size in animals
      preimplanted with RBEZ-FGF cells. Thus, FGF-1 gene delivery protected the
      developing striatum and hippocampus from quinolinate-induced volume loss by 62%
      and 100%, respectively. Intrastriatal quinolinate resulted in a significant
      decrease in density of NOS+ CA3 hippocampal neurons (-38%) without affecting the
      density of NOS+ neurons in hippocampal regions CA1, dentate gyrus or striatum.
      This response of CA3 NOS+ neurons appeared to be only partially reversed by FGF-1
      gene delivery. Our results show that intracerebral FGF-1 gene expression within
      the developing brain can protect striatum and hippocampus from quinolinate
      mediated injury.

PMID- 9767381
TI  - Re-establishment of direct synaptic connections between sensory axons and
      motoneurons after lesions of neonatal opossum CNS (Monodelphis domestica) in
      culture.
AB  - For functional recovery after spinal cord injury, regenerating fibres need to
      grow and to reform appropriate connections with their targets. The isolated
      central nervous system of neonatal opossums aged 1-9 days has been used to
      analyse the precision with which neurons become reconnected during regeneration.
      In culture these preparations maintain their electrical activity and show rapid
      outgrowth through spinal cord crushes or cuts. By recording electrically and by
      staining with horseradish peroxidase, we first demonstrated that direct reflex
      connections were already present at birth between sensory fibres in one segment
      and motoneurons in the same segment and in adjacent segments. As in previous
      experiments, 5 days after the spinal cord had been crushed, labelled sensory
      fibres grew across the lesion to reach the next segment (Woodward et al. (1993)
      J. Exp. Biol., 176, 77-88; Varga et al. (1995a) Eur. J. Neurosci., 7, 2119-2129,
      Varga et al. (1995b) Proc. Natl. Acad. Sci. USA, 92, 10959-10963). Beyond the
      lesion the labelled axons abruptly changed direction, traversed the spinal cord
      and terminated on labelled motoneurons in the ventral horn. In preparations that
      had regenerated dorsal root stimulation once again initiated ventral root
      reflexes. Electron micrographs revealed synapses made by labelled sensory axons
      on motoneurons. Double staining of growing sensory axons and radial glial fibres
      showed close association, suggesting guidance. These results indicate that the
      original pathway is re-established during repair and that appropriate connections
      are reformed after injury.

PMID- 9767382
TI  - Changes in morphology and behaviour of retinal growth cones before and after
      crossing the midline of the mouse chiasm - a confocal microscopy study.
AB  - The growth of retinal axons was investigated in different regions of the optic
      chiasm in C57 pigmented mouse embryos aged embryonic day 13 (E13) to E15.
      Individual retinal axons and their growth cones were labelled anterogradely by
      DiI and imaged using a confocal imaging system. In aldehyde-fixed embryos,
      retinal growth cones display a simple form in the optic nerve and become more
      complex in morphology in the chiasm. The complex form is particularly prominent
      in those axons that turn to the ipsilateral tract in the premidline region of
      chiasm. Moreover, complex growth cones are also commonly found in axons in the
      postmidline chiasm, which are markedly different in morphology from those axons
      in the premidline region, suggesting that the postmidline chiasm contains a novel
      environment for the pathfinding of retinal axons. In another experiment, the
      dynamic growth of retinal axons is studied in a brain slice preparation of the
      living retinofugal pathway. Retinal axons show an intermittent growth across the
      premidline and postmidline chiasm. Extensive remodelling of growth cone form
      followed by a shift in growth direction is commonly seen during the pause
      periods, indicating that signals that guide axon growth across the chiasm are not
      restricted to the midline, but are laid down throughout the chiasm. Moreover,
      dramatic changes in axon trajectory are noted first at the premidline chiasm
      where the uncrossed axons segregate from the crossed axons, and second at the
      postmidline chiasm where specific sorting of retinal axons according to their
      position in the dorsal ventral retinal axis and their ages are known to take
      place. These results show that there are two distinct environments, separated by
      the midline in the chiasm, where axons show different responses to local guidance
      cues and develop the distinct fibre orders.

PMID- 9767384
TI  - Potentiometric study of resting potential, contributing K+ channels and the onset
      of Na+ channel excitability in embryonic rat cortical cells.
AB  - Resting membrane potential (RMP), K+ channel contribution to RMP and the
      development of excitability were investigated in the entire population of acutely
      dissociated embryonic (E) rat cortical cells over E11-22 using a voltage
      sensitive fluorescent indicator dye and flow cytometry. During the period of
      intense proliferation (E11-13), two cell subpopulations with distinct estimated
      RMPs were recorded: one polarized at approximately -70 mV and the other
      relatively less-polarized at approximately -40 mV. Ca2+o was critical in
      sustaining the RMP of the majority of less-polarized cells, while the well
      polarized cells were characterized by membrane potentials exhibiting a
      approximately Nernstian relationship between RMP and [K+]o. Analysis of these two
      subpopulations revealed that > 80% of less-polarized cells were proliferative,
      while > 90% of well-polarized cells were postmitotic. Throughout embryonic
      development, the disappearance of Ca2+o-sensitive, less-polarized cells
      correlated with the disappearance of the proliferating population, while the
      appearance of the K+o-sensitive, well-polarized population correlated with the
      appearance of terminally postmitotic neurons, immuno-identified as BrdU-, tetanus
      toxin+ cells. Differentiating neurons were estimated to contain increased K+i
      relative to less-polarized cells, coinciding with the developmental expression of
      Cs+/Ba2+-sensitive and Ca2+-dependent K+ channels. Both K+ channels contributed
      to the RMP of well-polarized cells, which became more negative toward the end of
      neurogenesis. Depolarizing effects of veratridine, first observed at E11,
      progressively changed from Ca2+o-dependent and tetrodotoxin-insensitive to Na+o
      dependent and tetrodotoxin-sensitive response by E18. The results reveal a
      dynamic development of RMP, contributing K+ channels and voltage-dependent Na+
      channels in the developing cortex as it transforms from proliferative to
      primarily differentiating tissue.

PMID- 9767383
TI  - Dihydrokainate-sensitive neuronal glutamate transport is required for protection
      of rat cortical neurons in culture against synaptically released glutamate.
AB  - Glutamate transport in nearly pure rat cortical neurons in culture (less than
      0.2% astrocytes) is potently inhibited by dihydrokainate, l-serine-O-sulphate,
      but not by l-alpha-amino-adipate. This system allows for a test of the hypothesis
      that glutamate transport is important for protecting neurons against the toxicity
      of endogenous synaptically released glutamate. In support of this hypothesis, a
      20-24 h exposure to 1 mm dihydrokainate reduced cell survival to only 14.8 +/-
      9.8% in neuronal cultures (P < 0.001; n = 3), although it had no effect on
      neuronal survival in astrocyte-rich cultures (P > 0.05; n = 3). Dihydrokainate
      also significantly caused accumulation of glutamate in the extracellular medium
      of cortical neuronal cultures (6.6 +/- 4.9 micrometer, compared to 1.2 +/- 0.3
      micrometer in control, n = 14, P < 0.01). The neurotoxicity of dihydrokainate was
      blocked by 10 micrometer MK-801, 10 micrometer tetrodotoxin, and an enzyme system
      that degrades extracellular glutamate. The latter two also abolished the
      accumulation of glutamate in the extracellular medium. Dihydrokainate (1 mm)
      inhibited the 45calcium uptake stimulated by 30 micrometer N-methyl-d-aspartate
      (NMDA), but not by higher concentrations consistent with a weak antagonist action
      of dihydrokainate at the NMDA receptor. Whole cell recordings showed that 1 mm
      dihydrokainate produced approximately 25% inhibition of 30 micrometer NMDA
      induced current in cortical neurons. Dihydrokainate (1 mm) alone generated a
      small current (17% of the current produced by 30 micrometer NMDA) that was
      blocked by 30 micrometer 5,7-dichlorokynurenate and only weakly by 10 micrometer
      cyano-7-nitroquinoxaline-2,3-dione (CNQX). These results suggest that the
      toxicity of dihydrokainate in neuronal cultures is due to its ability to block
      glutamate transport in these cultures, and that dihydrokainate-sensitive neuronal
      glutamate transport may be important in protecting neurons against the toxicity
      of synaptically released glutamate.

PMID- 9767385
TI  - Two types of TTX-resistant and one TTX-sensitive Na+ channel in rat dorsal root
      ganglion neurons and their blockade by halothane.
AB  - The clinically employed general anaesthetic halothane was shown to exert action
      on the peripheral nervous system by suppressing spinal reflexes, but it is still
      unclear which mechanisms underlie this action. The present study addressed the
      question whether blockade of tetrodotoxin-sensitive (TTXs) and -resistant (TTXr)
      Na+-channels in rat dorsal root ganglia (DRG) neurons by halothane could explain
      its peripheral effects. Two types of TTXr Na+-currents, fast and slow, with
      distinct activation and inactivation kinetics were found in small (< 25
      micrometer) and medium sized (25-40 micrometer) DRG neurons. These currents were
      blocked by halothane with IC50 values of 5.4 and 7.4 mmol/L, respectively.
      Additionally, in a concentration-dependent manner halothane accelerated the
      inactivation kinetics of both currents and shifted the inactivation curves to
      more hyperpolarized potentials. Neither the activation curves of both TTXr Na+
      currents were influenced by halothane nor a voltage-dependent block at test
      potentials of the currents was seen. In contrast to that of fast current, the
      time-to-peak for slow current was changed in the presence of halothane. The TTXs
      Na+-current which prevailed in large neurons (> 40 micrometer) was blocked by
      halothane with an IC50 of 12.1 mmol/L. Its inactivation curve was also shifted to
      more hyperpolarized potentials and the inactivation kinetics accelerated with
      increasing halothane concentration. Similarly to TTXr Na+-currents, the
      activation curve of TTXs Na+-current and its time-to-peak were not influenced by
      halothane. It is suggested that two types of TTXr Na+-currents can explain the
      heterogeneity in kinetic data for TTXr Na+-currents. Furthermore, the incomplete
      blockade of Na+-currents might underlie the incomplete reduction of spinal
      reflexes at clinically used concentrations of halothane.

PMID- 9767386
TI  - Influence of Gz and Gi2 transducer proteins in the affinity of opioid agonists to
      mu receptors.
AB  - The affinity displayed by different opioids to mu receptors (ORs) was determined
      in mouse brain membranes incubated with antibodies directed to Galpha subunits of
      the guanine nucleotide-binding proteins Gi2 and Gz. Assays were conducted with 10
      pm 125I-Tyr27-beta-endorphin in the presence of 300 nm N, N-diallyl-Tyr-(alpha
      aminoisobutyric acid)2-Phe-Leu-OH (ICI-174 864), which prevented the binding of
      the iodinated neuropeptide to delta-ORs. Gpp(NH)p or the preincubation of mouse
      brain membranes with IgGs to Gi2alpha or Gzalpha subunits, promoted reductions in
      the affinity exhibited by the labelled probe. The potencies of beta-endorphin, [D
      Ala2,N-MePhe4,Gly-ol5]-enkephalin (DAMGO) and [D-Pen2,5]enkephalin (DPDPE) were
      reduced after impairing the coupling of mu-ORs to Gi2 or Gz proteins. Morphine
      showed a loss of affinity towards the mu-OR after preincubation of membranes with
      IgGs to Gzalpha subunits. However, it retained its potency after treatment with
      the anti-Gi2alpha IgGs. Conversely, [D-Ala2, D-Leu5]enkephalin (DADLE) and [D
      Ser2, Leu5] enkephalin-Thr6 (DSLET) showed decreased affinity to mu-ORs after
      treatment with anti-Gi2alpha IgGs, with no noticeable change following the use of
      IgGs to Gzalpha subunits. The affinity exhibited by the opioid antagonists
      naloxone, naltrexone, naloxonazine and [Cys2,Tyr3,Orn5, Pen7 amide]somatostatin
      analogue (CTOP) remained unchanged after either treatment. Therefore, the
      affinity exhibited by opioid agonists of mu-ORs, but not antagonists, depends on
      the nature of the G-protein coupled to these receptors.

PMID- 9767387
TI  - Associative and limbic regions of monkey striatum express high levels of dopamine
      D3 receptors: effects of MPTP and dopamine agonist replacement therapies.
AB  - The role of the dopamine D3 receptor subtype in the central nervous system is
      still not well understood. It has a distinct and restricted distribution, mostly
      associated with limbic territories of the striatum (olfactory tubercle and the
      shell of nucleus accumbens) in rat brain. Dopaminergic denervation induced by a 6
      hydroxydopamine lesion of the nigrostriatal system in rat down-regulates the
      expression of the D3 receptor. In the present study, we investigated the
      functional neuroanatomy of the dopamine D3 receptor subtype in the monkey (Macaca
      fascicularis) basal ganglia. We also studied the effect of administration of the
      dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and
      chronic D1-like (SKF 82958) or D2-like (cabergoline) agonist treatments on
      dopamine D3 receptor levels using receptor autoradiography. Our results clearly
      show that the distribution of D3 receptors in the monkey is more closely related
      to associative and limbic components of the striatum (caudate-putamen), as
      compared with its sensorimotor counterpart. Hence, D3 receptors may be more
      specifically involved in cognitive and motivational aspects of striatal
      functions, which are elaborated in prefrontal, temporal, parietal, cingulate and
      limbic cortices. Moreover, MPTP administration significantly decreased levels of
      D3 receptors and this effect was reversed or compensated by a chronic treatment
      with a D1-like, but not a D2-like, receptor agonist. The D3 receptor may
      represent an important target for adjunct or direct therapy designed to improve
      cognitive deficits observed in patients with Parkinson's disease, schizophrenia
      and other illnesses with frontal lobe cognitive disturbances.

PMID- 9767388
TI  - Intracellular Ca2+ during metabolic activation of KATP channels in spontaneously
      active dorsal vagal neurons in medullary slices.
AB  - Intracellular Ca2+ ([Ca2+]i) and membrane properties were measured in fura-2
      dialysed dorsal vagal neurons (DVN) spontaneously active at a frequency of 0.5-5
      Hz. [Ca2+]i increased by about 30 nm upon rising spike frequency by more than
      200% due to 20-50 pA current pulses or 10 micrometer serotonin. It fell by 30 nm
      upon block of spiking by current-injection, tetrodotoxin or Ni2+ and also during
      hyperpolarization due to gamma-aminobutyric acid or opening of adenosine
      triphosphate (ATP) -sensitive K+ (KATP) channels with diazoxide. KATP channel
      mediated hyperpolarizations during anoxia or cyanide produced an initial [Ca2+]i
      decrease which reversed into a secondary Ca2+ rise by less than 100 nm. Similar
      moderate rises of [Ca2+]i were observed during block of aerobic metabolism under
      voltage-clamp as well as in intact cells, loaded with fura-2 AM. The magnitude of
      the metabolism-related [Ca2+]i transients did not correlate with the amplitude of
      the KATP channel-mediated outward current. [Ca2+]i did not change during
      diazoxide-induced or spontaneous activation of KATP outward current observed in
      10% of cells after establishing whole-cell recording. Increasing [Ca2+]i with
      cyclopiazonic acid did not activate KATP channels. [Ca2+]i was not affected upon
      block of outward current with sulphonylureas, but these KATP channel blockers
      were effective to reverse inhibition of spike discharge and, thus, the initial
      [Ca2+]i fall upon spontaneous or diazoxide-, anoxia- and cyanide-induced KATP
      channel activation. A sulphonylurea-sensitive hyperpolarization and [Ca2+]i fall
      was also revealed in the early phase of iodoacetate-induced metabolic arrest,
      whereas after about 20 min, occurrence of a progressive depolarization led to an
      irreversible rise of [Ca2+]i to more than 1 micrometer. The results indicate that
      KATP channel activity in DVN is not affected by physiological changes of
      intracellular Ca2+ and the lack of a major perturbance of Ca2+ homeostasis
      contributes to their high tolerance to anoxia.

PMID- 9767389
TI  - Absence of short-wavelength sensitive cones in the retinae of seals (Carnivora)
      and African giant rats (Rodentia).
AB  - Most non-primate mammals have two types of cone: short-wavelength sensitive (S)
      and middle-to-long-wavelength sensitive (M/L) cones. In two species of African
      giant rats, Cricetomys gambianus and C. emini, and in two species of earless
      seals, Phoca hispida and P. vitulina, the retinal cone types and cone
      distributions were assessed with antibodies specific for the M/L-cone opsin and
      the S-cone opsin, respectively. All four species were found to completely lack S
      cones, while M/L-cones were present in low densities. M/L-cone densities, rod
      densities and cone/rod ratios were determined across the retina. Cone proportions
      are about 0.3-0. 5% in C. gambianus, 0.5-0.8% in C. emini, and 1.5-1.8% in P.
      hispida. An absence of S-cones has previously been reported in a few nocturnal
      mammals. As earless seals are visually active during night and day, we conclude
      that an absence of S-cones is not exclusively associated with nocturnality. The
      functional and comparative aspects are discussed.

PMID- 9767390
TI  - Quinolinic acid-induced inflammation in the striatum does not impair the survival
      of neural allografts in the rat.
AB  - It has been suggested that inflammation related to intracerebral transplantation
      surgery can affect the survival of intrastriatal neural allografts. To test this
      hypothesis, we transplanted dissociated embryonic mesencephalic tissue from one
      of two rat strains, Lewis (allogeneic grafts) or Sprague-Dawley (syngeneic
      grafts), to the striatum of Sprague-Dawley rats. The target striatum was either
      intact or had received a local injection of quinolinic acid 9 days earlier, in
      order to induce a marked inflammation. At 6 or 12 weeks after transplantation,
      there was no significant difference between the different groups regarding the
      number of surviving grafted tyrosine hydroxylase immunoreactive neurons. However,
      the graft volume of both the syngeneic and allogeneic implants was significantly
      larger in the quinolinate-lesioned than in the intact striatum. There were
      dramatically increased levels of expression of major histocompatibility complex
      class I and II antigens, marked infiltrates of macrophages, activated microglia
      and astrocytes, and accumulation of large numbers of CD4 and CD8 positive T
      lymphocytes in the quinolinate-lesioned striatum. In contrast, these
      immunological markers were much less abundant around both syngeneic and
      allogeneic grafts placed in intact striatum. We conclude that severe inflammation
      caused by quinolinic acid does not lead to rejection of intrastriatal neural
      allografts.

PMID- 9767391
TI  - Differential expression of alternative splice variants of beta-arrestin-1 and -2
      in rat central nervous system and peripheral tissues.
AB  - Members of arrestin/beta-arrestin protein family are thought to participate in
      agonist-mediated desensitization of G-protein-coupled receptors, including
      rhodopsin and beta2-adrenergic receptor. Unlike in human and cow, splice variants
      of this protein family in rat have not been studied extensively, and there has
      been no report on their existence at protein level. Hence, a previous report by
      others on the localization of both beta-arrestin-1 and -2 in a wide range of
      innervated rat tissues could imply their broad receptor specificity. In this
      report we show the presence of two alternatively spliced forms of beta-arrestin-1
      in several rat tissues using both reverse transcription-polymerase chain reaction
      and Western immunoblot. Splicing of beta-arrestin-1 pre-mRNA appears to be
      subject to differential regulation between the rat CNS and peripheral tissues. In
      contrast, we detected no splice variants of beta-arrestin-2 in rat. A comparison
      of the genomic DNA sequences of bovine and rat beta-arrestin-2, where the
      splicing of bovine beta-arrestin-2 mRNA has been reported, revealed a high degree
      of homology in their organization of exons and introns as well as certain
      differences that might be responsible for the different processing of beta
      arrestin-2 mRNA in the two species. Our two-dimensional isoelectric focusing gels
      using rat spinal cord and heart tissues demonstrate isoelectric heterogeneity of
      rat beta-arrestin-1, suggesting that beta-arrestin-1 is subject to post
      translational modification unlike beta-arrestin-2.

PMID- 9767392
TI  - Presynaptic protein interactions in vivo: evidence from botulinum A, C, D and E
      action at frog neuromuscular junction.
AB  - The present study examines the paralytic action of botulinum neurotoxins at their
      natural target, the neuromuscular junction. We asked whether syntaxin,
      synaptosome-associated protein of 25 kDa (SNAP-25) and vesicle-associated
      membrane protein (VAMP/synaptobrevin), the proteins proteolysed by botulinum, are
      susceptible to cleavage in frog nerve terminals, and whether they form complexes
      in vivo. In control terminals, the three SNAREs were distributed in broad bands
      at 1 micrometer intervals, at sites consistent with presynaptic Ca2+ channels.
      Within 3 h, botulinum A, C, D and E (BoNT/A/C/D/E) blocked nerve-evoked muscle
      contractions but their effects on substrate immunoreactivity varied. The effect
      of BoNT/A on either C-terminus or N-terminus immunoreactivity of SNAP-25 was
      undetectable after 3-h incubation, although C-terminus immunoreactivity was
      reduced after 24 h; N-terminus immunoreactivity was not affected even after 36 h.
      BoNT/E reduced C-terminus immunoreactivity of SNAP-25 1.5 h after toxin
      application when transmitter release was blocked, but required 24 h to reduce N
      terminus immunoreactivity. BoNT/C reduced syntaxin immunoreactivity after 24-h
      incubation but did not affect SNAP-25. BoNT/D reduced VAMP immunoreactivity at 3
      h while it increased SNAP-25 C-terminal staining fourfold. BoNT/A and BoNT/C
      applied together for 24 h reduced syntaxin immunoreactivity and that of both C-
      and N-terminus of SNAP-25, indicating that retention of SNAP-25 N-terminus after
      cleavage by BoNT/A depended on intact syntaxin. Therefore, we infer that SNAP-25
      interacts with VAMP and with syntaxin in vivo. Neurotoxin action abolished only
      40-60% of SNAP-25, VAMP or syntaxin immunoreactivity suggesting that distinct
      pools of these proteins, not immediately involved in triggered exocytosis, are
      resistant to proteolysis.

PMID- 9767393
TI  - The layout of orientation and ocular dominance domains in area 17 of strabismic
      cats.
AB  - In the primary visual cortex of strabismic cats, the elimination of correlated
      activity between the two eyes enhances the segregation of the geniculocortical
      afferents into alternating ocular dominance domains. In addition, both tangential
      intracortical fibres and neuronal synchronization are severely reduced between
      neurons activated by different eyes. Consequently, ocular dominance columns
      belonging to different eyes are functionally rather independent. We wondered
      whether this would also affect the organization of orientation preference maps.
      To this end, we visualized the functional architecture of area 17 of strabismic
      cats with both optical imaging based on intrinsic signals and double labelling of
      orientation and ocular dominance columns with [14C]2-deoxyglucose and
      [3H]proline. As expected, monocular iso-orientation domains had a patchy
      appearance and differed for the two eyes, leading to a clear segregation of the
      ocular dominance domains. Comparison of 'angle maps' revealed that orientation
      domains exhibit a pinwheel organization as in normally reared cats.
      Interestingly, the map of orientation preferences did not show any breaks at the
      borders between ocular dominance columns: iso-orientation domains were continuous
      across these borders. In addition, iso-orientation contours tended to cross the
      borders of adjacent ocular dominance columns at right angles. These data suggest
      that the basic relations between the layout of orientation maps and ocular
      dominance columns are not disturbed by artificial decorrelation of binocular
      input. Therefore in cat area 17, the orientation map does not seem to be modified
      by experience-dependent changes of thalamic input connections. This suggests the
      possibility that use-dependent rearrangement of geniculocortical afferents into
      ocular dominance columns is due to Hebbian modifications whereby postsynaptic
      responsivity is constrained by the scaffold of the orientation map.

PMID- 9767394
TI  - Axonal injury and peripheral nerve grafting in the thalamus and cerebellum of the
      adult rat: upregulation of c-jun and correlation with regenerative potential.
AB  - The protooncogene c-jun is highly expressed for long periods in axotomized PNS
      neurons. This may be related to their growth and regeneration. In contrast,
      axotomized CNS neurons show only a small and transient upregulation of c-jun. It
      has been suggested that there may be a correlation between this failure to
      maintain high levels of c-jun expression after axotomy and abortive CNS axonal
      regeneration. We have studied, by in situ hybridization and immunohistochemistry,
      the c-jun response after stab wound lesion, and after peripheral nerve grafting
      in the thalamus and cerebellum of the adult rat. A lesion elicits upregulation of
      c-jun in thalamic neurons ipsilateral to the lesion. This is most evident and
      prolonged in neurons such as those of the thalamic reticular nucleus, which have
      an established propensity to regenerate. After peripheral nerve grafting, the c
      jun response in thalamic neurons is enhanced, mostly in neurons which have axons
      regenerating along the grafts. These neurons also upregulate growth-associated
      protein 43 (GAP-43). By comparison, injured Purkinje cells of the cerebellum
      which do not regenerate their axons along a graft, do not upregulate either c-jun
      or GAP-43, although they increase their expression of p75. Thus CNS neurons able
      to regenerate their axons along a peripheral nerve graft are those in which c-jun
      is induced after injury, and c-jun may play a critical role in the control of
      gene programs for axonal regeneration. Moreover, the observed differences in the
      ability of CNS neurons to regenerate their axons may relate to a difference in
      their intrinsic molecular response to axotomy.

PMID- 9767395
TI  - Spatial-frequency tuning and geniculocortical projections in the visual cortex
      (areas 17 and 18) of the pigmented ferret.
AB  - We have examined the spatial-frequency selectivity of neurons in areas 17 and 18
      of the adult pigmented ferret, by measuring how the amplitude of response depends
      on the spatial-frequency of moving sinusoidal gratings of optimal orientation and
      fixed contrast. Neurons in area 17 of the ferret respond optimally to low spatial
      frequencies [average 0.25 cycles per degree (c/deg)], much lower than the optima
      for cat area 17. The tuning curves are of the same form as those found in cat and
      monkey: unimodal with bandwidths in the range 0.8-3.5 octaves. Neurons in area 18
      of the ferret respond optimally to even lower spatial frequencies (average 0.087
      c/deg) than area 17 neurons, and the distributions of optimal spatial frequency
      for areas 17 and 18 hardly overlap. In both cortical areas, the bandwidth of the
      tuning curves is inversely correlated with optimal spatial frequency. This marked
      difference in tuning between the two cortical areas is probably attributable to
      differential geniculo-cortical projections. Small injections of fluorescent latex
      microspheres or horseradish peroxidase (HRP) were made into area 17 or area 18 in
      order to investigate the populations of geniculate neurons projecting to the two
      cortical areas. After injections into area 17, labelled neurons are found
      predominantly in the geniculate A layers, with a few neurons labelled in the C
      layers. Conversely, after an area 18 injection, similar numbers of labelled
      neurons are found in the C layers as in the A layers. Soma-size analysis of the
      neurons in the A-layers suggests the existence of two populations of relay
      neurons, which project differentially to areas 17 and 18. The different
      geniculate inputs and the different spatial-frequency tuning in areas 17 and 18
      may imply that the two cortical areas process visual information more in parallel
      than in series.

PMID- 9767396
TI  - Learning-specific, time-dependent increases in hippocampal Ca2+/calmodulin
      dependent protein kinase II activity and AMPA GluR1 subunit immunoreactivity.
AB  - Ca2+/calmodulin-dependent protein kinase II (CAMK II) and one of its target,
      alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), glutamate
      receptors have been shown to participate in both long-term potentiation (LTP) in
      the hippocampus, and in spatial, as well as in a variety, of learning paradigms.
      Recently, we were able to demonstrate that the intrahippocampal infusion of a
      specific inhibitor of CAMK II (KN62) provoked full retrograde amnesia of an
      inhibitory avoidance learning in rats when given immediately, but not 120 or 240
      min, after training. Furthermore, this task is accompanied by a rapid, selective
      and reversible increase in hippocampal [3H] AMPA receptor binding. Here we report
      the effect of this aversively motivated learning task on CAMK II activity, and
      AMPA GluR1 subunit phosphorylation and immunoreactivity in the hippocampus. One
      trial inhibitory avoidance training is associated with a learning-specific, time
      dependent increase (25-78%) in both total and Ca2+-independent activities of CAMK
      II in the hippocampus of rats killed immediately (0 min), but not 120 min, after
      training. In addition, immunoblotting experiments showed an increment in the
      amount of the alpha-subunit of CAMK II at 0, 30 and 120 min after training. An
      increase in the in vitro phosphorylation of alpha- and beta-subunits of CAMK II
      was also observed in hippocampal synaptosomal membranes (SPM) of trained rats
      killed immediately and 30 min post-training. In addition, inhibitory avoidance is
      accompanied by a 20% increase in GluR1 phosphorylation and a 33% increase in
      GluR1 immunoreactivity 120 min after training. No significant changes were
      observed in shocked animals. Phosphorylation of hippocampal SPM from naive
      control animals in conditions suitable for CAMK II activation resulted in a large
      increase in the density of [3H] AMPA binding (+ 100%). Taken together, these
      findings confirm and extend previous data suggesting that CAMK II and AMPA
      glutamate receptors in the hippocampus participate in the early phase of memory
      formation of an inhibitory avoidance learning.

PMID- 9767397
TI  - An animal model of autism: behavioural studies in the GS guinea-pig.
AB  - Autism is a human behavioural pathology marked by major difficulties in abnormal
      socialization, language comprehension and stereotypic motor patterns. These
      behavioural abnormalities have been associated with corticocerebral and
      cerebellar abnormalities in autistic patients, particularly in vermal folia VI
      and VII. Progress in understanding this disease has been hindered by the absence
      of a non-primate animal model. GS guinea-pigs are a partially inbred, non-ataxic
      guinea-pig strain with cerebellar and corticocerebral abnormalities similar to
      those reported to exist in human patients with autism. In order to determine if
      GS guinea-pigs represent an animal model of autism, their behaviour was compared
      with that of Hartley strain guinea-pigs. GS animals learned a motor task
      significantly more rapidly than Hartley guinea-pigs, but performed it in a more
      stereotypic manner and were less influenced by environmental stimuli than
      Hartleys. GS animals exhibited significantly less exploratory behaviour in a
      novel environment and were significantly less responsive to 50-95 dBA pure tones
      than Hartley guinea-pigs. In a social interaction assay, GS guinea-pigs
      interacted significantly less frequently with each other or with Hartley guinea
      pigs than Hartleys did under the same conditions. GS behaviour thus exhibits
      autistic-like behaviour patterns: motor stereotypy, lack of exploration and
      response to environment and poor social interaction. Coupled with the
      neuropathological findings, this abnormal behaviour suggests that GS guinea-pigs
      could be a useful animal model of autism.

PMID- 9767398
TI  - 5HT1A-receptors and behaviour under chronic stress: selective counteraction by
      testosterone.
AB  - Behaviour of chronically stressed male tree shrews is characterized by a
      reduction in scent marking, self-grooming and overall locomotor activity. It has
      been proposed that this subordination behaviour is related to the down-regulation
      of 5HT1A-receptors occurring in distinct brain regions of the animals. The high
      cortisol concentrations which accompany chronic stress are supposed to induce
      5HT1A-receptor down-regulation. Because chronic stress in males also decreases
      androgen levels we investigated whether behaviour and 5HT1A-receptor expression
      could be renormalized by testosterone replacement. Male tree shrews were
      submitted to subordination stress for 28 days, while during the last 18 days, one
      group was treated with testosterone and one with vehicle. Scent marking, self
      grooming, and overall locomotor activity were monitored, and cortisol levels were
      measured in morning urine during the whole experiment. Brain 5HT1A-receptors were
      quantified by in vitro receptor autoradiography. Although in subordinate animals
      cortisol levels remained high during the testosterone treatment, 5HT1A-receptors
      in the hippocampal formation and the occipital cortex were renormalized to
      control levels by the androgen, but 5HT1A-receptors in the ventromedial thalamic
      nucleus did not return to base line levels. Scent marking and self-grooming
      behaviour were both renormalized by testosterone, but overall locomotor activity
      did not return to base line levels. These data indicate that a balance between
      glucocorticoids and androgens is necessary to maintain 'normal' numbers of the
      monoamine receptors. The fact that both, 5HT1A-receptors and certain behaviours
      can be renormalized by the sex steroid supports the view that 5HT1A-receptor are
      involved in the regulation of stress behaviour. However, the fact that overall
      locomotor activity was not returned to baseline indicates that different types of
      behaviour are distinctly regulated.

PMID- 9767399
TI  - L-DOPA-induced dyskinesia in the rat is associated with striatal overexpression
      of prodynorphin- and glutamic acid decarboxylase mRNA.
AB  - Rats sustaining unilateral near-complete 6-hydroxydopamine lesions of the
      mesostriatal dopamine pathway received daily injections of 3, 4 dihydroxyphenyl-l
      alanine (L-DOPA, 8 mg/kg plus 15 mg/kg benserazide) for 3 weeks. During this
      period, about 50% of the rats gradually developed abnormal involuntary movements,
      lasting for 2-3 h following each L-DOPA dose. Rats were killed 3 days after the
      last L-DOPA injection, and sections through the striatum were processed for in
      situ hybridization histochemistry. Within the L-DOPA-treated group, levels of
      preproenkephalin (PPE) mRNA, glutamic acid decarboxylase (GAD67) mRNA, and
      prodynorphin (PDyn) mRNA in the dopamine-denervated caudate-putamen, as well as
      GAD67 mRNA expression in the globus pallidus ipsilateral to the 6-hydroxydopamine
      (6-OHDA) lesion, were higher in dyskinetic than non-dyskinetic animals, and
      positively correlated with the rats' dyskinesia scores. By contrast, striatal
      preprotachykinin mRNA expression and D2 receptor-radioligand binding were not
      significantly associated with dyskinesia. Among all these markers, PDyn mRNA
      levels showed the most pronounced treatment-dependence (three times higher in the
      L-DOPA-treated group than in saline-injected lesion-only controls), and the
      strongest correlation with the rats' dyskinesia scores (r2 = 0.82). However, a
      multiple regression equation including the three factors, GAD67 mRNA levels in
      the GP, GAD67 mRNA in the lateral CPu, and striatal PDyn mRNA, gave a better fit
      for dyskinesia scores than PDyn mRNA alone (r2 = 0.92). The results show that L
      DOPA-induced dyskinesia is associated with overexpression of PDyn and GAD67 mRNA
      in the striatal projection neurons, and GAD67 mRNA levels in the globus pallidus.
      Due to its treatment-dependent expression, and strong correlation with the
      associated dyskinetic symptoms, striatal PDyn mRNA, in particular, may play a
      role in the mechanisms of behavioural sensitization brought about by the drug.

PMID- 9767400
TI  - The cytokine network of wallerian degeneration: IL-10 and GM-CSF.
AB  - Wallerian degeneration (WD) is the inflammatory response of peripheral nerves to
      injury. Evidence is provided that granulocyte macrophage colony stimulating
      factor (GM-CSF) contributes to the initiation and progression of WD by activating
      macrophages and Schwann, whereas IL-10 down-regulates WD by inhibiting GM-CSF
      production. A significant role of activated macrophages and Schwann for future
      regeneration is myelin removal by phagocytosis and degradation. We studied the
      timing and magnitude of GM-CSF and IL-10 production, macrophage and Schwann
      activation, and myelin degradation in C57BL/6NHSD and C57BL/6-WLD/OLA/NHSD mice
      that display normal rapid-WD and abnormal slow-WD, respectively. We observed the
      following events in rapid-WD. The onset of GM-CSF production is within 5 h after
      injury. Production is steadily augmented during the first 3 days, but is
      attenuated thereafter. The onset of production of the macrophage and Schwann
      activation marker Galectin-3/MAC-2 succeeds that of GM-CSF. Galectin-3/MAC-2
      production is up-regulated during the first 6 days, but is down-regulated
      thereafter. The onset of myelin degradation succeeds that of Galectin-3/MAC-2,
      and is almost complete within 1 week. IL-10 production displays two phases. An
      immediate low followed by a high that begins on the fourth day, reaching highest
      levels on the seventh. The timing and magnitude of GM-CSF production thus enable
      the rapid activation of macrophages and Schwann that consequently phagocytose and
      degrade myelin. The timing and magnitude of IL-10 production suggest a role in
      down-regulating WD after myelin is removed. In contrast, slow-WD nerves produce
      low inefficient levels of GM-CSF and IL-10 throughout. Therefore, deficient IL-10
      levels cannot account for inefficient GM-CSF production, whereas deficient GM-CSF
      levels may account, in part, for slow-WD.

PMID- 9767401
TI  - GABA-dependent generation of ectopic action potentials in the rat hippocampus.
AB  - Intracellular recordings from CA3 pyramidal cells of rat hippocampus in a slice
      preparation revealed the occurrence of interictal epileptiform discharges and
      synchronous GABA-mediated potentials during application of 4-aminopyridine (4AP,
      50 micrometer). The synchronous GABA-mediated potential consisted of a sequence
      of early hyperpolarization, long-lasting depolarization (LLD), and late
      hyperpolarization. Action potentials of variable amplitude occurred at the peak
      of the early hyperpolarization and during the LLD rising phase (48 of 64 cells);
      they were not prevented by membrane hyperpolarization and displayed inflections
      that were reminiscent of the initial segment-somatodendritic (IS-SD)
      fractionation. Interictal discharges were blocked by excitatory amino acid
      receptor antagonists, while both GABA-mediated potentials and action potentials
      of variable amplitude continued to occur (n = 10). The latter events were still
      recorded in the presence of the GABAB receptor antagonist CGP-35348 (0.5-1 mm, n
      = 4), but were abolished by the GABAA receptor antagonist bicuculline methiodide
      (BMI, 10 micrometer, n = 5). Localized application of BMI (20 micrometer, n = 6)
      or tetrodotoxin (TTX, 5 micrometer, n = 3) to the CA1 stratum radiatum blocked
      the variable amplitude action potentials; these effects were not seen when BMI (n
      = 4) or TTX (n = 4) were applied to the CA3 stratum radiatum, although both
      procedures made LLDs disappear. Our findings indicate that action potentials of
      variable amplitude recorded from CA3 pyramidal cells in the 4AP model are
      generated at or near the terminal region of the Schaffer collaterals and that
      they represent TTX-sensitive ectopic events. These action potentials are
      generated at this site by a BMI-sensitive (and thus GABAA-mediated) mechanism. We
      propose that the ectopic action potentials reflect an increased excitability of
      axon terminals that is presumably caused by [K+]o elevations associated with the
      4AP-induced synchronous GABA-mediated potential.

PMID- 9767402
TI  - Differential acetylcholine and GABA release from cultured chick retina cells.
AB  - In the present work we investigated the mechanisms controlling the release of
      acetylcholine (ACh) and of gamma-aminobutyric acid (GABA) from cultures of
      amacrine-like neurons, containing a subpopulation of cells which are
      simultaneously GABAergic and cholinergic. We found that 81.2 +/- 2.8% of the
      cells present in the culture were stained immunocytochemically with an antibody
      against choline acetyltransferase, and 38.5 +/- 4.8% of the cells were stained
      with an antibody against GABA. Most of the cells containing GABA (87.0 +/- 2.9%)
      were cholinergic. The release of acetylcholine and GABA was mostly Ca2+
      dependent, although a significant release of [3H]GABA occurred by reversal of its
      transporter. Potassium evoked the Ca2+-dependent release of [3H]GABA and
      [3H]acetylcholine, with EC50 of 31.0 +/- 1.0 mm and 21.6 +/- 1.1 mm,
      respectively. The Ca2+-dependent release of [3H]acetylcholine was significantly
      inhibited by 1 micrometer tetrodotoxin and by low (30 nm) omega-conotoxin GVIA
      (omega-CgTx GVIA) concentrations, or by high (300 nm) nitrendipine (Nit)
      concentrations. On the contrary, the release of [14C]GABA was reduced by 30 nm
      nitrendipine, or by 500 nm omega-CgTx GVIA, but not by this toxin at 30 nm. The
      release of either transmitters was unaffected by 200 nm omega-Agatoxin IVA (omega
      Aga IVA), a toxin that blocks P/Q-type voltage-sensitive Ca2+ channels (VSCC).
      The results show that Ca2+-influx through omega-CgTx GVIA-sensitive N-type VSCC
      and through Nit-sensitive L-type VSCC induce the release of ACh and GABA.
      However, the significant differences observed regarding the Ca2+ channels
      involved in the release of each neurotransmitter suggest that in amacrine-like
      neurons containing simultaneously GABA and acetylcholine the two
      neurotransmitters may be released in distinct regions of the cells, endowed with
      different populations of VSCC.

PMID- 9767403
TI  - Influence of handedness on peripheral auditory asymmetry.
AB  - It is well established that in humans many differences between right- and left
      handers, anatomical, physiological and functional, exist. Left- and mixed
      handedness is associated with greater bihemispheric representation of cognitive
      functions than in right-handers. Several studies indicate a left-right asymmetry
      in the function of hearing pathways between cochlea and auditory cortex, and
      furthermore, that this asymmetry is associated with handedness. Our investigation
      focuses on the medial olivo-cochlear system, which has been demonstrated to be
      more effective in the right than left ear in right-handers. The aim of the study
      was to investigate this auditory efferent system asymmetry according to
      handedness, gender, eyedness, footedness and the presence of spontaneous
      otoacoustic emissions. The medial efferent system has been found to be more
      effective in the right than left ear in right-handers, while functioning
      symmetrically in left-handers. Furthermore, the olivo-cochlear system, assumed to
      be involved in basic language processing, shows an asymmetrical pattern of
      functioning influenced by handedness as well as by hemispheric language
      representation. Reverse medial efferent system asymmetry was observed in left
      handers compared to that in right-handers, on condition that only left-handed
      males were considered, or that the left-handers were also left-eyed, or that
      spontaneous otoacoustic emissions were present in the left ear of the left
      handers, or when only left-handers without mixed-handers were considered.

PMID- 9767404
TI  - Short communication: hippocampal neuronal activity and imprinting in the behaving
      domestic chick.
AB  - The hippocampus of the chick projects to the intermediate and medial part of the
      hyperstriatum ventrale (IMHV) which stores information acquired through the
      learning process of imprinting. We have investigated whether the response
      properties of hippocampal neurons are similar to those of IMHV neurons. Chicks
      were imprinted by exposure, one group (n = 7) to a rotating red box (RB), the
      other (n = 5) to a rotating blue cylinder (BC). Four chicks were untrained. The
      following day, when the chicks were approximately 48 h old, neuronal activity was
      recorded in the left hippocampus. The proportion of neurons responding to the RB
      and that to the BC in untrained chicks were compared with the proportions in
      trained birds. (i) In RB-trained chicks both the proportion responding to the RB
      and that to the BC were significantly increased. (ii) In BC-trained chicks no
      significant effect on these proportions was found. Of the responsive neurons some
      were colour (red or blue) sensitive and others were shape (box or cylinder)
      sensitive; the proportions so responsive were not influenced by training
      condition. Certain neurons responded significantly differently when a stimulus
      was 0.5 m or 2 m from the chick (35%; d-sensitive); very few neurons were
      equivalently responsive to a stimulus at both distances (3%; d-invariant). These
      proportions were not significantly affected by training condition. Hippocampal
      responses are compared with those in the left IMHV. It is concluded that IMHV
      responses do not passively reflect those of hippocampal neurons.

PMID- 9767405
TI  - Short communication: long- but not medium-term retention of olfactory memories in
      honeybees is impaired by actinomycin D and anisomycin.
AB  - Although work in a wide variety of species and paradigms has demonstrated that
      long-term memory is sensitive to the blocking of protein synthesis, previous
      studies have suggested that the honeybee might represent an exception to this
      rule. Retention tested one day after training was not impaired by the inhibition
      of translation by cycloheximide. Using blockers of either transcription
      (actinomycin D) or translation (anisomycin), we present experiments that
      reconcile this unusual finding by testing over longer retention periods.
      Honeybees were conditioned to associate an odourant with a sucrose reward.
      Typically, this leads to stable retention over days. However, injection of either
      drug led to lower retention after 4 days, whereas retention after 2 or sometimes
      even 3 days was unaffected. This dissociates two forms of memory: a protein
      synthesis-independent, medium-term memory (up to 3 days) and a protein synthesis
      dependent, long-term memory lasting for at least 4 days.

PMID- 9767406
TI  - Short communication: transforming growth factor-beta mediates the neurotrophic
      effect of fibroblast growth factor-2 on midbrain dopaminergic neurons.
AB  - Fibroblast growth factor (FGF)-2 is an established neurotrophic factor for
      dopaminergic (DAergic) neurons in the ventral midbrain. Its survival and
      differentiation-promoting effects on DAergic neurons in vitro and in vivo are
      crucially dependent on the presence, numerical expansion and maturation of
      astroglial cells. We show now that transforming growth factor (TGF)-beta, an
      established trophic factor for DAergic neurons and product of astroglial cells,
      mediates the trophic effect of FGF-2 on DAergic neurons cultured from the
      embryonic rat midbrain floor. Antibodies to TGF-beta that neutralize the isoforms
      -beta1, -beta2 and -beta3 abolish the trophic effect of FGF-2. FGF-2 increases
      TGF-beta3 mRNA and amounts of biologically active TGF-beta determined in a mink
      lung epithelial cell assay in a time-dependent manner. FGF-2 also induces levels
      of active TGF-beta in neonatal rat astrocytes cultured from midbrain, striatum
      and cortex. We conclude that TGF-beta is required for mediating the survival
      promoting effect of FGF-2 on DAergic and, possibly, cortical and striatal neurons
      grown in the presence of glial cells.

PMID- 9767408
TI  - Immuno-stimulatory effects of bacterial-derived plasmids depend on the nature of
      the antigen in intramuscular DNA inoculations.
AB  - The CpG motifs of bacterial-derived plasmids augment antigen-specific immune
      responses and steer those responses towards the T helper 1 (Th1) type. In this
      study, we have addressed the immuno-stimulatory effect of intramuscular co
      administration of CpG motifs containing vector DNA on the modulation of immune
      responses to the haemagglutinin (HA) and the nucleoprotein (NP) proteins of
      influenza virus. The co-administration of vector DNA with a HA-encoding plasmid
      DNA showed a significant enhancement in the total IgG response, the generation of
      cytotoxic T lymphocyte (CTL), and the T-cell proliferative response. In the case
      of NP-encoding plasmid DNA inoculations, the co-administration of vector DNA
      slightly decreased the total IgG response, although the IgG2a/IgG1 ratio and the
      CTL responses to NP were significantly increased. These observations suggest that
      the immuno-stimulatory effects of bacterial-derived plasmids depend upon the
      nature of the co-administered antigen.

PMID- 9767407
TI  - Short communication: protection of axotomized retinal ganglion cells by
      adenovirally delivered BDNF in vivo.
AB  - Following intraorbital transection of the optic nerve (ON) in rats, more than 80%
      of the retinal ganglion cell (RGC) population die by apoptosis within 14 days.
      Repeated intraocular injection of brain-derived neurotrophic factor (BDNF) has
      been efficient in enhancing RGC survival following ON axotomy. The present study
      was designed to define a potential survival-promoting effect of adenovirally
      administered BDNF on axotomized RGCs. A single injection of an adenoviral vector
      expressing the human BDNF gene from a CMV promoter/enhancer (Ad-BDNF) enhanced
      RGC survival 14 days after axotomy by 40.3%. Moreover, a combinatory treatment
      regimen consisting of intraocular Ad-BDNF administration and systemic application
      of the free radical scavenger, N-tert-butyl-(2-sulphophenyl)-nitrone (S-PBN),
      enhanced RGC survival by 63.0%. Our data demonstrate that adenoviral delivery of
      neurotrophic factors to the vitreous body is a feasible approach for the
      prevention of axotomy-induced RGC death. Further, as shown for S-PBN, therapeutic
      regimens that combine local virus-mediated gene delivery with systemic
      administration of protective compounds, may offer promising strategies for future
      treatment also in human neurodegenerative conditions.

PMID- 9767409
TI  - Maintenance of granulocyte numbers during acute peritonitis is defective in
      galectin-3-null mutant mice.
AB  - Galectin-3, also known as the macrophage marker Mac-2, is a member of a family of
      structurally related animal lectins that exhibit specificity for beta
      galactosides. In order to investigate the role of galectin-3 in acute
      inflammation, we have compared the number of leucocytes present in the peritoneal
      cavity of wild type and galectin-3 null mutant mice after intraperitoneal (i.p.)
      injection of thioglycolate broth. At day 1 after injection, we found no
      difference in the recruitment of mononuclear phagocytes and granulocytes to the
      peritoneal cavity. However, 4 days after thioglycolate injection, galectin-3
      mutant mice exhibited a significantly reduced number of recoverable granulocytes
      compared to wild-type animals. As mutant granulocytes did not exhibit an
      accelerated rate of apoptosis and their uptake by macrophages appeared to be
      unaffected by the mutation, the phenotype described here suggests that galectin-3
      participates in an additional level of control during the resolution of acute
      inflammation.

PMID- 9767410
TI  - Treatment with recombinant granulocyte colony-stimulating factor (Filgrastin)
      stimulates neutrophils and tissue macrophages and induces an effective non
      specific response against Mycobacterium avium in mice.
AB  - A role of neutrophils in the host response against Mycobacterium avium (MAC) has
      recently been suggested. To investigate this matter further, we determined the
      effect of granulocyte colony-stimulating factor (G-CSF) on the outcome of MAC
      infection in mice. C57BL/6bg+/bg- black mice were intravenously infected with 1 x
      10(7) MAC and then divided into four experimental groups to receive G-CSF as
      follows: (i) 10 micrograms/kg/day; (ii) 50 micrograms/kg/day; (iii) 100
      micrograms/kg/day; (iv) placebo control. Mice were killed at 2 and 4 weeks of
      treatment to determine the bacterial load of liver and spleen. Treatment with G
      CSF at both 10 and 50 micrograms/kg/day doses significantly decreased the number
      of viable bacteria in liver and spleen after 2 weeks (approximately 70.5% and
      69.0%, respectively), and after 4 weeks (approximately 53% and 52%, respectively,
      P < 0.05 compared with placebo control). Treatment with 100 micrograms/kg/day did
      not result in decrease of bacterial colony-forming units in the liver and spleen
      after 4 weeks. Administration of G-CSF induced interleukin-10 (IL-10) and IL-12
      production by splenocytes. To examine if the protective effect of G-CSF was
      accompanied by the activation of phagocytic cells, blood neutrophils and splenic
      macrophages were purified from mice receiving G-CSF and their ability to kill MAC
      was examined ex vivo. Neutrophils and macrophages from G-CSF-treated mice were
      able to inhibit the growth of or to kill MAC ex vivo, while phagocytic cells from
      untreated control mice had no anti-MAC effect. These results suggest that
      activation of neutrophils appears to induce an effective non-specific host
      defence against MAC, and further studies should aim for better understanding of
      the mechanisms of protection.

PMID- 9767411
TI  - Functional immaturity of rat alveolar macrophages during postnatal development.
AB  - Alveolar macrophages (AM) are important in the regulation of immune responses in
      the lung, through their role as scavenger cells and through the production of
      many bioactive factors. Because in early infancy pulmonary infections are a
      recurrent problem, we studied the postnatal functional maturation of AM in a rat
      model. AM were isolated from rat lungs by bronchoalveolar lavage at several time
      intervals after birth and tested for their ability to ingest Escherichia coli in
      the presence of surfactant protein A (SP-A). Furthermore, their capacity to
      produce nitric oxide (NO) and interleukin-1 beta (IL-1 beta) after in vitro
      lipopolysaccharide (LPS) stimulation was analysed, as well as their capacity to
      downregulate proliferation of T cells from both mature and neonatal rats. SP-A
      mediated phagocytosis of E. coli by AM was reduced in 14-day-old neonatal rats,
      as compared with mature rats (P < or = 0.05). Also the IL-1 beta production by
      rat AM after LPS stimulation was impaired at 14 days of age, as compared with IL
      1 beta production by AM from mature rats (P < or = 0.05). In contrast, the LPS
      induced NO production by rat AM as well as the capacity to inhibit T-cell
      proliferation were well developed at all ages tested. In conclusion, during
      postnatal development the rat AM is functionally immature, with respect to
      phagocytosis and secretion of inflammatory mediators. These differences may
      underly the enhanced susceptibility to pulmonary infections as found in human
      neonates.

PMID- 9767412
TI  - Specific antigen targeting to surface IgE and IgG on mouse bone marrow-derived
      mast cells enhances efficiency of antigen presentation.
AB  - The discovery that bone marrow-derived mast cells can express major
      histocompatibility complex class II molecules and act as antigen-presenting cells
      prompted us to evaluate this function when antigen is internalized through fluid
      phase endocytosis or via specific uptake by using IgG and IgE antibodies. This
      study was performed using a specific T-cell hybridoma developed against Lol p 1,
      the major allergen of grass pollen Lolium perenne. Expression of Fc gamma R and
      Fc epsilon RI by mast cells led us to investigate the influence of IgG- and IgE
      targeted antigen on the antigen-presenting function of mast cells.
      Internalization of Lol p 1 through different specific IgG monoclonal antibodies
      (mAb) resulted in the activation of Lol p 1-specific T-cell hybridoma at
      concentrations about 100-fold less than that required for T-cell stimulation by
      uncomplexed antigen. IgE-complexed Lol p 1, which facilitates trapping of antigen
      by mast cells, induced an accelerated and more efficient antigen-presenting
      capacity of mast cells than that obtained with uncomplexed antigen. However,
      aggregation of anti-dinitrophenyl (DNP) IgE mAb by the irrelevant antigen DNP
      human serum albumin did not substantially increase the capacity of mast cells to
      present Lol p 1 to T cells. This suggests that the mere aggregation of Fc epsilon
      RI is not sufficient for enhanced antigen presentation mediated by IgE. Tissue
      distribution and strategic location of mast cells at the mucosal barriers and
      their capacity to process the antigen through efficient fluid-phase pinocytosis
      as well as IgG- and IgE-dependent targeting of antigens provide mast cells with a
      prominent role in immune surveillance.

PMID- 9767413
TI  - Modulation of antigen-specific T-cell activation in vitro by taurine chloramine.
AB  - Taurine chloramine (TauCl) is produced during inflammation by reaction of
      hypochlorous acid (HOCl) with taurine, the most abundant free amino acid in
      neutrophils. We previously reported that TauCl inhibits the generation of
      macrophage inflammatory mediators such as nitric oxide, prostaglandin E2 (PGE2),
      tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). In this study,
      the activity of TauCl in modulating T-cell activation was investigated. Treatment
      of T cells with TauCl (0.1-0.3 mM), prior to activation, was found to inhibit
      interleukin-2 (IL-2) release in response to both mitogen and antigen stimulation.
      Similarly, pretreatment of A-20 antigen presenting cells (APCs), at low cell
      numbers, was found to inhibit their ability to process and present ovalbumin
      (OVA) to a specific T-cell hybridoma. In contrast, pretreatment of higher numbers
      of A-20 cells with TauCl in the presence of OVA enhanced subsequent presentation
      of OVA. Finally, OVA modified with TauCl was processed and presented more
      efficiently than native OVA. Thus, TauCl is able to modulate induction of a
      specific adaptive immune response at several independent points of the overall
      antigen-presenting pathway.

PMID- 9767414
TI  - Staphylococcal enterotoxin B-induced T-cell anergy is mediated by regulatory T
      cells.
AB  - Naive T cells mount a vigorous proliferative response to superantigen (SAg)
      stimulation in vivo. The proliferative response is followed by a partial deletion
      of responder T cells. Part of the deletion process has recently been attributed
      to the action of regulatory cytotoxic T cells that recognize major
      histocompatibility complex (MHC) class I-associated antigen receptor determinants
      on the target cell surface. Responder T cells that survived the SAg response were
      found to be incapable of generating a secondary proliferative response to a SAg
      challenge. We show here that this 'anergy' is enforced by CD8-positive regulatory
      suppressive T cells. These regulatory cells inhibit cell division of preactivated
      T cells but not the Sag response of naive T cells. Regulatory T cells are not
      generated in the presence of cyclosporin A and, once activated, become
      inactivated or deleted when restimulated in the presence of this
      immunosuppressive drug.

PMID- 9767415
TI  - Lipopolysaccharide-induced production of tumour necrosis factor and interleukin-1
      is differentially regulated at the receptor level: the role of CD14-dependent and
      CD14-independent pathways.
AB  - Cytokine production induced via CD14-dependent and CD14-independent pathways was
      investigated in mouse peritoneal macrophages incubated with lipopolysaccharide
      (LPS) or lipid A. Different LPS receptors appear to be responsible for production
      of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 alpha (IL-1 alpha)
      and IL-1 beta. TNF-alpha production is essentially CD14 dependent, both in the
      presence or absence of plasma. In the presence of plasma, endotoxin-induced IL-1
      production is mediated by CD14-dependent mechanisms, while in its absence both
      CD14-dependent and CD14-independent pathways are involved. Lipid A stimulates
      cytokine synthesis through both CD14-dependent and CD14-independent mechanisms,
      but its action is weaker than that of LPS, indicating that the polysaccharide
      moiety may be necessary for proper stimulation of mouse macrophages by endotoxin.

PMID- 9767416
TI  - Peroxynitrite-induced thymocyte apoptosis: the role of caspases and poly (ADP
      ribose) synthetase (PARS) activation.
AB  - The mechanisms by which immature thymocyte apoptosis is induced during negative
      selection are poorly defined. Reports demonstrated that cross-linking of T-cell
      receptor leads to stromal cell activation, expression of inducible nitric oxide
      synthase (iNOS) and, subsequently, to thymocyte apoptosis. Therefore we examined,
      whether NO directly or indirectly, through peroxynitrite formation, causes
      thymocyte apoptosis. Immuno-histochemical detection of nitrotyrosine revealed in
      vivo peroxynitrite formation in the thymi of naive mice. Nitrotyrosine, the
      footprint of peroxynitrite, was predominantly found in the corticomedullary
      junction and the medulla of naive mice. In the thymi of mice deficient in the
      inducible isoform of nitric oxide synthase, considerably less nitrotyrosine was
      found. Exposure of thymocytes in vitro to low concentrations (10 microM) of
      peroxynitrite led to apoptosis, whereas higher concentrations (50 microM)
      resulted in intense cell death with the characteristics of necrosis. We also
      investigated the effect of poly (ADP-ribose) synthetase (PARS) inhibition on
      thymocyte apoptosis. Using the PARS inhibitor 3-aminobenzamide (3-AB), or
      thymocytes from PARS-deficient animals, we established that PARS determines the
      fate of thymocyte death. Suppression of cellular ATP levels, and the cellular
      necrosis in response to peroxynitrite were prevented by PARS inhibition.
      Therefore, in the absence of PARS, cells are diverted towards the pathway of
      apoptotic cell death. Similar results were obtained with H2O2 treatment, while
      apoptosis induced by non-oxidative stimuli such as dexamethasone or anti-FAS
      antibody was unaffected by PARS inhibition. In conclusion, we propose that
      peroxynitrite-induced apoptosis may play a role in the process of thymocyte
      negative selection. Furthermore, we propose that the physiological role of PARS
      cleavage by apopain during apoptosis may serve as an energy-conserving step,
      enabling the cell to complete the process of apoptosis.

PMID- 9767417
TI  - Immunolocalization of protease-activated receptor-2 in skin: receptor activation
      stimulates interleukin-8 secretion by keratinocytes in vitro.
AB  - The protease-activated receptor-2 (PAR-2) is a seven transmembrane domain
      receptor related to the thrombin receptor, which is activated in vitro by
      cleavage by trypsin. Affinity-purified rabbit IgG raised against a peptide
      corresponding to the trypsin cleavage site of PAR-2 was used for an
      immunohistochemical study of skin. The expression of PAR-2 in epidermis was
      striking, with keratinocytes showing abundant intercellular and cytoplasmic
      staining. Basal cells showed the strongest staining intensity and the stratum
      corneum was negative. Staining with control IgG used at the same concentration
      was consistently negative. The functional expression of PAR-2 by the simian virus
      transformed human skin keratinocyte cell line SVK14 was demonstrated by Northern
      blot analysis, flow cytometric analysis and the measurement of intracellular
      calcium. Treatment of SVK14 with trypsin or a receptor agonist peptide (SLIGKV
      NH2) caused a dose-dependent increase in the secretion of the chemokine
      interleukin-8 (IL-8) in vitro. The effect of the peptide was specific, since
      control acetylated peptide was without activity. We conclude that PAR-2 is highly
      expressed by epidermal keratinocytes and receptor activation in vitro leads to
      increased IL-8 secretion by keratinocytes. These data raise the possibility that
      PAR-2 may play a role in epidermal homeostasis and inflammatory conditions.

PMID- 9767418
TI  - Lymphocyte surface marker and cytokine expression in peripheral and mucosal lymph
      nodes.
AB  - Lymphocyte populations, adhesion molecule and cytokine expression were determined
      in lymph nodes draining peripheral (popliteal and prescapular) or mucosal
      (abomasal and jejunal) tissue sites using flow cytometry analysis, immunostaining
      and cytokine-specific reverse-transcription-polymerase chain reaction (RT-PCR).
      Similar proportions of lymphocyte subpopulations were present in all lymph nodes
      except for immunoglobulin A+ (IgA+) B cells which were only present in
      significant numbers in the gastrointestinal lymph nodes. Peripheral lymph nodes
      contained a significantly higher number of CD4+ cells expressing L-selectin and
      beta 1-integrin than mucosal lymph nodes while the alpha 4-integrin chain was
      expressed at similar levels in all lymph nodes. The peripheral node adressin
      recognized by the MECA 79 monoclonal antibody (mAb) was mainly expressed on
      peripheral lymph node vessels. RT-PCR analysis showed that interleukin (IL)-10
      and IL-4 were preferentially induced in the gastrointestinal lymph nodes while IL
      2 and interferon-gamma (IFN-gamma) were induced in all lymph nodes after
      polyclonal stimulation. These results indicate that there are substantial
      differences in the cell populations and microenvironments of lymph nodes draining
      mucosal and peripheral tissue sites in adult sheep.

PMID- 9767419
TI  - Expression of CD69 activation marker by endometrial granulated lymphocytes
      throughout the menstrual cycle and in early pregnancy.
AB  - Flow cytometry studies of first-trimester normal human decidua have proposed that
      a proportion of endometrial granulated lymphocytes (eGL), the predominant
      leucocyte population in early human pregnancy, co-express CD69. The purpose of
      this study was to investigate CD69 expression by immunohistochemistry throughout
      the menstrual cycle and in first-trimester human decidua and to determine whether
      CD69 expression by eGL is an in vivo characteristic or whether the antigen is
      acquired in vitro after tissue disaggregation and cell purification. Single
      immunoenzymatic and double immunofluorescence labelling of tissue sections,
      supplemented with double immunoenzymatic staining of purified eGL and flow
      cytometry, indicated that eGL do not co-express CD69 in situ but that they
      acquire the molecule in vitro after cell purification and culture.

PMID- 9767420
TI  - The effect of renin-angiotensin system inhibitors on pro- and anti-inflammatory
      cytokine production.
AB  - The balance between pro- and anti-inflammatory cytokines has been implicated in
      the pathogenesis of infectious and auto-immune diseases, and its modulation has
      been proposed as a potential therapeutic target. The results reported in the
      present study show that modulators of the renin-angiotensin system, such as the
      angiotensin-converting enzyme (ACE)-inhibitor captopril and the angiotensin II
      receptor type I antagonist valsartan, have potent inhibitory effects on the
      lipopolysaccharide (LPS)-stimulated production of pro-inflammatory cytokines
      tumour necrosis factor (TNF) and interleukin-1 (IL-1) in vitro. The anti
      inflammatory cytokine IL-1Ra is increased by captopril, whereas IL-6 production
      is decreased by valsartan. These effects are exerted mainly at high
      concentrations of the drugs. Administration of one dose of captopril or valsartan
      in therapeutic dosages to patients with essential hypertension did not influence
      LPS-stimulated production of cytokines by whole blood. In conclusion, despite
      inhibitory effects on pro-inflammatory cytokine production in vitro, it is
      unlikely that captopril or valsartan could be used in anticytokine therapeutic
      strategies in vivo.

PMID- 9767421
TI  - Role of mRNA stability in the different patterns of cytokine production by CD4+
      cells from young and old mice.
AB  - CD4+ cells from young (3 months) and old (19 months) mice were stimulated by
      plate-bound anti-CD3 monoclonal antibody (mAb) alone or also by soluble anti-CD28
      mAb. Supernatants were analysed by enzyme-linked immunosorbent assay (ELISA) to
      determine cytokine concentrations. Total RNA was extracted from cells, reverse
      transcribed and the cDNA amplified by polymerase chain reaction (PCR) to evaluate
      the amount of specific mRNA. The results indicate that anti-CD3 alone is not
      sufficient to induce interleukin-2 (IL-2) production in CD4+ cells from both
      young and old mice. However, anti-CD28, together with anti-CD3 mAb, induces a
      much higher production of IL-2 in CD4+ cells from young as compared with old
      mice. Conversely, interferon-gamma (IFN-gamma) production is also induced by anti
      CD3 alone and is higher in CD4+ cells from old as compared with young mice. Upon
      addition of anti-CD28 mAb, IFN-gamma production increases in both groups, but it
      remains much higher in old than in young mice. Also the production of IL-4 and IL
      10 is induced by anti-CD3 mAb but it is increased by the addition of anti-CD28
      mAb. CD4+ cells from old mice produce more IL-4 and IL-10 as compared with cells
      from young mice. The amounts of cytokine specific mRNA in CD4+ cells from young
      and old mice parallel the cytokine levels in culture supernatants. Results on the
      mRNA turnover indicate that when CD4+ cells are stimulated by anti-CD3 or
      costimulated also by anti-CD28 mAb, the IFN-gamma, IL-4 and IL-10 specific mRNAs
      are more stable in old than in young mice, suggesting that mRNA stability has a
      relevant role in the different patterns of cytokine production.

PMID- 9767422
TI  - Synergistic augmentative effect of interleukin-10 and CD27/CD70 interactions on B
      cell immunoglobulin synthesis.
AB  - Interleukin-10 (IL-10) is a potent cytokine that regulates immunoglobulin
      synthesis by B cells. CD27/CD70 interactions by direct cell-to-cell contact are
      also needed to produce substantial amounts of immunoglobulin. We have
      investigated the effects of IL-10 and CD27/CD70 interactions on the
      immunoglobulin synthesis. In the presence of IL-10 stimulation, the production of
      IgG, IgM and IgA was increased synergistically by the addition of CD27 ligand
      (CD70)-transfectants in a dose-dependent manner, which was completely blocked by
      anti-CD70 monoclonal antibody. In contrast, CD70-transfectants additively
      enhanced the immunoglobulin production in the presence of IL-2, IL-4, or IL-6.
      The synergistic enhancement of the immunoglobulin production by IL-10 and CD70
      transfectants was remarkable in highly purified CD27+ B cells, but there was no
      immunoglobulin production in CD27- B cells. Furthermore, by the addition of CD70
      transfectants, the synthesis of IgG1, IgG2, IgG3 and IgG4 was also enhanced in
      the presence of IL-10. On the other hand, IL-10 diminished CD27 expression in B
      cells. B-cell proliferation was augmented by CD70-transfectants with IL-10 or IL
      10 plus IL-2. The addition of IL-2 further augmented the immunoglobulin
      production which was synergistically enhanced by IL-10 and CD27 triggering. Taken
      together, the co-operative response to IL-10 and CD27/CD70 interactions regulates
      B-cell immunoglobulin production.

PMID- 9767423
TI  - Lymphotoxin-alpha is an important autocrine factor for CD40 + interleukin-4
      mediated B-cell activation in normal and atopic donors.
AB  - Stimulation of human B cells with anti-CD40 + interleukin-4 (IL-4) results not
      only in proliferation and immunoglobulin E (IgE)-production, but also increased
      production of the cytokine lymphotoxin-alpha (LT-alpha) (formerly also known as
      tumour necrosis factor-beta (TNF-beta)). Here, we studied the role of LT-alpha
      (TNF-beta) in B cells following stimulation with anti-CD40 + IL-4 from normal
      versus atopic donors. Anti-CD40 + IL-4 stimulation of peripheral blood
      mononuclear cells (PBMC) from atopic donors resulted in enhanced production of
      soluble LT-alpha (TNF-beta) and increased membrane LT-alpha (TNF-beta) expression
      on the B cells compared with normal donors. Functional evaluation of LT-alpha
      (TNF-beta) in CD40 + IL-4-stimulated B cells shows that recombinant LT-alpha (TNF
      beta) induces proliferation of B cells and enhances CD40 + IL-4-mediated B-cell
      proliferation and IgE synthesis in both normal and atopic donors in a dose
      dependent manner. These findings were supported by semiquantitative analysis of
      epsilon-germline transcripts using reverse transcription-polymerase chain
      reaction (RT-PCR) showing increased epsilon-germline transcription in the
      presence of LT-alpha. Furthermore, addition of anti-LT-alpha (anti-TNF-beta) to
      CD40 + IL-4-stimulated B cells partially inhibited proliferation and IgE
      synthesis in a dose-dependent manner indicating a role of endogenous LT-alpha
      (TNF-beta) production by B cells during continued CD40 + IL-4 stimulation. These
      data suggest that LT-alpha (TNF-beta) plays a potentially significant role during
      B-cell proliferation and IgE synthesis. Moreover, LT-alpha (TNF-beta) production
      seems to be differentially regulated in B cells from normal and atopic donors.

PMID- 9767424
TI  - Increased serum IgG1 levels and reduced numbers of B-1 B cells in DBA/2J mice.
AB  - B-cell heterogeneity studies have historically focused upon BALB/c mice and their
      derivatives. In contrast, the B cells of DBA/2J mice, a prototype strain for the
      study of the endogenous minor lymphocyte stimulatory (Mls) viral superantigen Mls
      1a, have not been extensively investigated. DBA/2J B cells, by functioning as Mls
      1a antigen-presenting cells, influence their own differentiation and diversity by
      inducing the proliferation and differentiation of specific CD4 T-cell subsets. In
      this report, the B cells of DBA/2J and BALB/c mice were compared for their
      ability to restore B-cell function in severe combined immunodeficient (SCID)
      recipients. Although spleen and bone marrow cells from these strains exhibited
      similar restoration of serum IgM production, the transfer of DBA/2J B cells into
      SCID mice led to greater IgG1 production. The peritoneal cells of DBA/2J mice
      consisted of a lower percentage of B-1 B cells and were less capable of restoring
      B-cell function after transfer into SCID recipients. These differences are
      discussed with respect to the possible role of viral superantigens in influencing
      B-lymphocyte diversity.

PMID- 9767425
TI  - Human/BALB radiation chimera engrafted with splenocytes from patients with
      idiopathic thrombocytopenic purpura produce human platelet antibodies.
AB  - We have previously shown that lethally irradiated normal strains of mice,
      radioprotected with severe combined immunodeficient (SCID) bone marrow, can be
      engrafted with human peripheral blood mononuclear cells (PBMC). The human/mouse
      radiation chimera can mount marked humoral and cellular responses to recall
      antigens, as well as primary responses. In the present study, we adoptively
      transferred splenocytes from patients with chronic immune thrombocytopenic
      purpura (ITP) into lethally irradiated BALB/c mice, radioprotected with SCID bone
      marrow. High titres of total human immunoglobulin appeared as early as 2 weeks
      post-transplant and declined after 6 weeks, while human anti-human platelet
      antibodies were detected 2-8 weeks after the transfer of splenocytes. The
      immunoglobulin G (IgG) fraction contained antibodies against glycoprotein (GP)
      IIb/IIIa (CD41) or GPIb/IX (CD42). The human platelet antibodies showed a low
      level of cross-reactivity with mouse platelets, and thrombocytopenia in the
      animals was not observed. Splenocytes from individual ITP patients differed in
      their capacity to produce either human platelet antibodies or total human
      immunoglobulin. Furthermore, antibodies produced in the murine system were not
      always identical to the original antibodies present in the serum of the patients.
      The study of the serological aspects of autoantibodies against human platelets in
      an animal model might be useful for the investigation of potential therapeutics
      in ITP.

PMID- 9767426
TI  - Antibodies to the costimulatory molecule CD86 interfere with ultraviolet
      radiation-induced immune suppression.
AB  - Although almost all of the energy contained within the ultraviolet (UV)
      wavelengths of solar radiation is absorbed within the epidermis and upper layers
      of the dermis, UV irradiation can suppress the immune response to antigens
      introduced at distant, non-irradiated body sites. The production of immune
      modulatory cytokines, such as interleukin-10 (IL-10), by UV-irradiated
      keratinocytes and its effect on T helper type 1 (Th1)/Th2-cell balance are
      thought to play a major role in the induction of systemic immune suppression.
      Because it is suggested that costimulatory molecules, such as CD80 and CD86,
      differentially stimulate Th1 and Th2 cells we wished to investigate the role of
      these costimulatory molecules in the activation of immune suppression. We
      injected UV-irradiated mice with monoclonal antibodies to CD80 and CD86 and asked
      what effect, if any, this would have on UV-induced immune suppression. Anti-CD86,
      but not anti-CD80 or control rat IgG, blocked UV-induced immune suppression.
      Moreover, monoclonal anti-CD86 blocked the induction of suppressor T cells
      normally found in the spleens of the UV-irradiated mice. Monoclonal anti-CD86
      also reversed the UV-induced impairment of systemic antigen-presenting cell
      function. IL-10 was detectable in the serum of UV-irradiated mice as compared
      with normal controls, and injecting UV-irradiated mice with anti-CD86, but not
      anti-CD80 or control rat IgG, blocked the secretion of IL-10 into the serum. We
      propose that UV exposure favours costimulation by CD86, which enhances the
      production of serum IL-10, thus suppressing Th1-cell-mediated immune reactions.

PMID- 9767427
TI  - Role of GM1 binding in the mucosal immunogenicity and adjuvant activity of the
      Escherichia coli heat-labile enterotoxin and its B subunit.
AB  - Escherichia coli (E. coli) heat-labile toxin (LT) is a potent mucosal immunogen
      and immunoadjuvant towards co-administered antigens. LT is composed of one copy
      of the A subunit, which has ADP-ribosylation activity, and a homopentamer of B
      subunits, which has affinity for the toxin receptor, the ganglioside GM1. Both
      the ADP-ribosylation activity of LTA and GM1 binding of LTB have been proposed to
      be involved in immune stimulation. We investigated the roles of these activities
      in the immunogenicity of recombinant LT or LTB upon intranasal immunization of
      mice using LT/LTB mutants, lacking either ADP-ribosylation activity, GM1-binding
      affinity, or both. Likewise, the adjuvant properties of these LT/LTB variants
      towards influenza virus subunit antigen were investigated. With respect to the
      immunogenicity of LT and LTB, we found that GM1-binding activity is essential for
      effective induction of anti-LTB antibodies. On the other hand, an LT mutant
      lacking ADP-ribosylation activity retained the immunogenic properties of the
      native toxin, indicating that ADP ribosylation is not critically involved.
      Whereas adjuvanticity of LTB was found to be directly related to GM1-binding
      activity, adjuvanticity of LT was found to be independent of GM1-binding
      affinity. Moreover, a mutant lacking both GM1-binding and ADP-ribosylation
      activity, also retained adjuvanticity. These results demonstrate that neither ADP
      ribosylation activity nor GM1 binding are essential for adjuvanticity of LT, and
      suggest an ADP-ribosylation-independent adjuvant effect of the A subunit.

PMID- 9767429
TI  - Intranasal administration of human immunodeficiency virus type-1 (HIV-1) DNA
      vaccine with interleukin-2 expression plasmid enhances cell-mediated immunity
      against HIV-1.
AB  - DNA vaccine against human immunodeficiency virus type-1 (HIV-1) can induce
      substantial levels of HIV-1-specific humoral and cell-mediated immunity. To
      develop more potent HIV-1 DNA vaccine formulations, we used a murine model to
      explore the immunomodulatory effects of an interleukin-2 (IL-2) expression
      plasmid on an HIV-1 DNA vaccine following intranasal administration of the
      combination. When the vaccine and expression plasmid were incorporated into
      cationic liposomes and administered to mice, the HIV-1-specific delayed-type
      hypersensitivity response and cytotoxic T lymphocyte activity were significantly
      increased. Restimulated immune lymphoid cells showed enhanced production of both
      IL-2 and interferon-gamma and reduced secretion of IL-4. The level of total
      antibody to HIV-1 antigen was not greatly changed by coadministration of the DNA
      vaccine and IL-2 expression plasmid. An analysis of serum HIV-1-specific IgG
      subclasses showed a significant drop in the IgG1/IgG2a ratio in the group that
      received the plasmid-vaccine combination. These results demonstrate that the IL-2
      expression plasmid strongly enhances the HIV-1-specific immune response via
      activation of T helper type-1 cells.

PMID- 9767430
TI  - Human and murine T-cell responses to allelic forms of a malaria circumsporozoite
      protein epitope support a polyvalent vaccine strategy.
AB  - Mouse models and a recent vaccine trial have indicated the importance of T-cell
      immunity to the circumsporozoite protein (CSP) of malaria sporozoites. One of the
      major impediments for the development of a CSP-based vaccine is that human T-cell
      epitopes, identified on the CSP, span regions of significant point mutational
      polymorphism. Studies with human and mouse T-cell clones have indicated that this
      polymorphism affects T-cell cross-reactivity to Th2R and Th3R, the two most
      polymorphic and immunodominant epitopes. We extend this observation with
      polyclonal human T-cell lines, from 11 donors, raised to known variants of Th2R.
      These lines showed limited but variable cross-reactivity with the heterologous
      peptides. T cells from B10.A4(R) (I-Ak) mice immunized with each of 18 natural
      variants of Th2R indicated a similar, limited, cross-reactivity. I-Ak competition
      assays showed that a number of peptides were unable to bind because of a single
      polymorphic residue. In both the human and mouse assays, analysis of the
      sequences of immunogenic cross-reactive and non-cross-reactive peptides suggested
      that the individual polymorphic residues affect the three-dimensional
      conformation of the peptide within the major histocompatibility complex (MHC)
      groove in an, as yet, unpredictable way. These observations argue that design of
      an epitope able to generate broad cross-reactivity is, to date, not possible.
      However, despite the limited cross-reactivity of the individual human T-cell
      lines, most of the donors had T-cell repertoires capable of recognizing all or
      nearly all of the variants tested, which supports a strategy using a multivalent
      vaccine.

PMID- 9767428
TI  - Dose-dependent mechanisms relate to nasal tolerance induction and protection
      against experimental autoimmune encephalomyelitis in Lewis rats.
AB  - Nasal administration of soluble antigens is an exciting means of specifically
      down-regulating pathogenic T-cell reactivities in autoimmune diseases. The
      mechanisms by which nasal administration of soluble antigens suppresses
      autoimmunity are poorly understood. To define further the principles of nasal
      tolerance induction, we studied the effects of nasal administration of myelin
      basic protein (MBP) on experimental autoimmune encephalomyelitis (EAE) in the
      Lewis rat. EAE is a CD4+ T-cell-mediated animal model for human multiple
      sclerosis. Nasal administration of guinea-pig (gp)-MBP at a dose as low as 30
      micrograms/rat can completely prevent gp-MBP-induced EAE, whereas nasal
      administration of bovine (b)-MBP is not effective even at a much higher dosage.
      Cellular immune responses, as reflected by T-cell proliferation and interferon
      gamma (IFN-gamma)-ELISPOT, were suppressed in rats receiving the two different
      doses (30 and 600 micrograms/rat) of gp-MBP, but not after administration of b
      MBP. Rats tolerized with both doses of gp-MBP had also abrogated MBP-induced IFN
      gamma mRNA expression in popliteal and inguinal lymph node mononuclear cells
      compared with rats receiving phosphate-buffered saline nasally. However, adoptive
      transfer revealed that only spleen mononuclear cells from rats pretreated with a
      low dose, but not from those pretreated with a high dose, of gp-MBP transferred
      protection to actively induced EAE. Low-dose (30 micrograms/rat) gp-MBP-tolerized
      rats also had high numbers of interleukin-4 (IL-4) mRNA-expressing lymph node
      cells, while high-dose (600 micrograms/rat) gp-MBP-tolerized rats had low numbers
      of IL-4 mRNA-expressing lymph node cells. Our data suggest an exquisite
      specificity of nasal tolerance. Dose-dependent mechanisms also relate to nasal
      tolerance induction and protection against EAE in the Lewis rat.

PMID- 9767431
TI  - Antigen detection in vivo after immunization with different presentation forms of
      rabies virus antigen, II. Cellular, but not humoral, systemic immune responses
      against rabies virus immune-stimulating complexes are macrophage dependent.
AB  - In this paper we describe the effect of depletion of splenic macrophages on the
      uptake, and immune response against, different formulations of rabies virus
      antigen. Splenic macrophages were removed by intravenous injection with
      clodronate liposomes. beta-propiolacton inactivated rabies virus (RV-BPL) and
      immune-stimulating complexes (iscom) containing these antigens were given to
      macrophage-depleted and control mice. In the absence of phagocytic cells in the
      spleen, antigen is still trapped in the red pulp and to a lesser extent in the
      peri-arteriolar lymphocyte sheaths (PALS) for both antigen formulations. The
      localization pattern in the main area of immune response induction, namely the
      follicles, was unaltered after macrophage depletion. Functionally, the depletion
      of splenic and liver macrophages had no influence on the induction of specific
      antibody responses in both RV-BPL or RV-iscom immunized mice, even though the
      latter presentation form was clearly associated with specific localization in the
      marginal metallophillic macrophages. In RV-BPL immunized mice, macrophage
      depletion had no influence on proliferative T-cell responses. However, macrophage
      depleted mice that were immunized with RV-iscom showed a significant decrease in
      proliferative T-cell responses. These results confirm existing ideas on the
      spleen as a physical filter rather than an induction site for humoral responses
      and shed new light on the efficient role of iscoms as antigen-presenting moieties
      in relation to their specific in vivo localization patterns and partial
      macrophage dependency.

PMID- 9767432
TI  - Cross-linking of Fc(gamma)-receptor on monocytes inhibits hepatitis C virus
      specific cytotoxic T-lymphocyte induction in vitro.
AB  - In hepatitis C virus (HCV) infection, immune complex (IC)-type virus particles
      are frequently observed in circulation. The IC leads to cross-linking of Fcgamma
      receptors (FcgammaR) on monocytes and exerts immunoinhibitory function. To test
      the roles of IC in HCV-specific cytotoxic T lymphocyte (CTL) induction, we
      generated HCV CTL from peripheral blood mononuclear cells of chronic hepatitis C
      patients with or without HCV-IC- or immunoglobulin G (IgG)-coated culture plates
      and compared their lytic activities. HCV-IC or adherent IgG, which induces
      FcgammaR cross-linking, significantly reduced CTL activity. Expression of B7-1 on
      monocytes decreased on adherent IgG. In addition, tumour necrosis factor-alpha
      (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) production increased
      from cells on adherent IgG and their mRNA expression in monocytes was enhanced.
      Anti-TNF-alpha antibody during induction on adherent IgG inhibited lysis;
      however, anti-TGF-beta completely reversed its inhibitory effect. These results
      demonstrated that HCV-IC or adherent IgG impaired HCV-CTL induction in vitro. The
      FcgammaR-mediated CTL suppression occurred via decreased expression of monocyte
      B7-1 and/or enhanced production of TGF-beta1.

PMID- 9767433
TI  - Different roles are played by alpha beta and gamma delta T cells in acquired
      immunity to Chlamydia trachomatis pulmonary infection.
AB  - Using gene knockout and wild-type C57BL/6 mice, we examined the role of alpha
      beta and gamma delta T cells in the resolution of Chlamydia trachomatis mouse
      pneumonitis (MoPn) biovar pulmonary infection. The results show that alpha beta T
      cell-deficient (alpha-/-) mice, when compared with wild-type control mice, have
      dramatically increased mortality rate and greater in vivo growth of MoPn. The
      alpha beta T-cell-deficient mice were as susceptible to MoPn infection as T- and
      B-lymphocyte-deficient (RAG-1-/-) mice. Moreover, both alpha beta T-cell
      deficient and RAG-1 mutant mice failed to mount delayed-type hypersensitivity
      (DTH) responses to organism-specific challenge and showed undetectable interferon
      gamma (IFN-gamma) production by spleen cells upon in vitro organism-specific
      restimulation. In contrast, gamma delta T-cell-deficient mice exhibited intact
      DTH responses and their mortality rate and in vivo chlamydial growth were
      comparable to those in wild-type controls. More interestingly, gamma delta T-cell
      deficient mice showed significantly higher levels of IFN-gamma production than
      did wild-type mice. The data indicate that the alpha beta T cell is the major T
      cell population for acquired immunity to chlamydial infection and that gamma
      delta T cells may play an ancillary role in regulating the magnitude of alpha
      beta T-cell responses.

PMID- 9767434
TI  - African trypanosome infections in mice that lack the interferon-gamma receptor
      gene: nitric oxide-dependent and -independent suppression of T-cell proliferative
      responses and the development of anaemia.
AB  - Infection of mice with African trypanosomes leads to a severe immunosuppression,
      mediated by suppressor macrophages. Using ex vivo macrophage culture and in vivo
      cell transfer, it has been shown that nitric oxide (NO) is a potent effector
      product of these cells and causes both lymphocyte unresponsiveness and
      dyserythropoiesis. We explored the role of NO in vivo during trypanosome
      infection using mice with a disrupted interferon-gamma-receptor gene, which were
      unable to respond with macrophage activation and NO synthesis. These mice were
      less effective at controlling parasitaemia than the wild types, but showed an
      improved splenic T-cell responsiveness and reduced anaemia during the early
      stages of infection. The data indicate that, in the mouse, NO is a significant
      mediator of immunosuppression only in early infection. Beyond day 10 of
      infection, NO-independent mechanisms are of primary significance and the control
      of parasitaemia and T-cell responsiveness are not directly related.

PMID- 9767435
TI  - Endogenous IL-10 regulates IFN-gamma and IL-5 cytokine production and the
      granulomatous response in Schistosomiasis mansoni-infected mice.
AB  - In murine Schistosomiasis mansoni circumovum, granuloma formation is regulated by
      pro- and anti-inflammatory cytokines. Among the latter, interleukin-10 (IL-10)
      has been shown to regulate the inflammatory response. In this study we examined
      the role of endogenously produced IL-10 in T-helper 1 (Th1)- and Th2-type
      cytokine production and granuloma formation. The dynamics of IL-10 production
      through the course of the infection were different in granuloma versus splenic
      cells. In the former, production peaked during the early developmental stage (6
      weeks of infection) of the granuloma and then declined. In splenocytes production
      peaked at 12 weeks, before down-modulation of the granuloma response. In the
      developing granuloma both macrophages and T cells secreted IL-10. In anti-IL-10
      monoclonal antibody (mAb)-supplemented granuloma cell cultures endogenous IL-10
      mediated regulation of interferon-gamma (IFN-gamma) was manifest only at 6 weeks;
      that of IL-2 continued throughout the infection (6-20 weeks). IL-4 production was
      unaffected, but IL-5 production was regulated at the 6 and 8 weeks time point.
      Splenocytes showed regulation of IFN-gamma and IL-2 production at the peak of the
      granulomatous response (8 weeks). IL-4 production was not regulated, whereas IL-5
      production was regulated only at 6 weeks. Repeated injections of anti-IL-10 mAb
      given to mice at 6, 12 or 20 weeks of the infection significantly enhanced liver
      and lung granuloma growth, tissue eosinophilia, and IFN-gamma, IL-5 production at
      the early developmental phase (6 weeks) of the lesions. Thus, in schistosome
      infected mice endogenous IL-10 is shown to regulate Th1- and Th2-type cytokine
      production and granuloma formation during the early Th0/Th1 phase of the immune
      response.

PMID- 9767436
TI  - Interferon-gamma-activated primary enterocytes inhibit Toxoplasma gondii
      replication: a role for intracellular iron.
AB  - Toxoplasma gondii is an obligate intracellular parasite that infects a wide
      variety of nucleated cells in its numerous intermediate hosts including man. The
      oral route is the natural portal of entry of T. gondii. Ingested organisms are
      released from cysts or oocysts within the gastrointestinal tract and initially
      invade the intestinal epithelium. We show that T. gondii invades and proliferates
      in cultured primary rat enterocytes, obtained with an original procedure.
      Activation of the enterocytes with rat recombinant interferon-gamma (IFN-gamma)
      inhibits T. gondii replication, the inhibition being dose dependent. Neither
      nitrogen and oxygen derivatives nor tryptophan starvation appear to be involved
      in the inhibition of parasite replication by IFN-gamma. Experiments using Fe2+
      salt, carrier and chelator indicate that intracellular T. gondii replication is
      iron dependent, suggesting that IFN-gamma-treated enterocytes inhibit T. gondii
      replication by limiting the availability of intracellular iron to the parasite.
      Our data show that enterocytes probably play a major role on mucosal surfaces as
      a first line of defence against this coccidia, and possibly other pathogens,
      through an immune mechanism. The results suggest that limiting the availability
      of iron could represent a broad antimicrobial mechanism through which the
      activated enterocytes exert control over intracellular pathogens.

PMID- 9767437
TI  - ICAM-1 costimulation induces IL-2 but inhibits IL-10 production in superantigen
      activated human CD4+ T cells.
AB  - We have previously reported that costimulatory pathways including B7-CD28 and
      lymphocyte function-associated antigen-3 (LFA-3)-CD2 shape distinct activation
      profiles in human CD4+ T cells. We now show that superantigen (SAg), in
      combination with intracellular adhesion molecule-1 (ICAM-1) costimulation drives
      a proliferative response accompanied by high levels of interleukin-2 (IL-2) and
      moderate levels of interferon-gamma (IFN-gamma) and tumour necrosis factor (TNF).
      This response profile differs from that observed in B7 or LFA-3 costimulated T
      cells because our previous results showed that B7-CD28 costimulation was
      accompanied by high levels of IL-2, IFN-gamma and TNF, whereas LFA-3 was a potent
      inducer of IFN-gamma and TNF, but had little influence on IL-2 production. The
      ICAM-1-induced IL-2 production could efficiently be abrogated with monoclonal
      antibody (mAb) against ICAM-1 or LFA-1, showing that the activation is dependent
      of a functional ICAM-1-LFA-1 pathway. SAg-induced IL-2, IFN-gamma and TNF were
      detected in both CD4+ and CD8+ T cells, whereas production of IL-10 was
      restricted to CD4+ T cells. A major finding in the present study was that ICAM-1
      costimulation strongly inhibits IL-10 production in CD4+ T cells. Our data
      demonstrate that ICAM-1 costimulation is sufficient to induce large amounts of IL
      2. The presence of ICAM-1 results in suppression of IL-10 production in T helper
      (Th) cells, which may favour the development of Th1 and not Th2 T cells.

PMID- 9767439
TI  - Bolus injection of aqueous antigen leads to a high density of T-cell-receptor
      ligand in the spleen, transient T-cell activation and anergy induction.
AB  - In vivo anergy can be modelled by administration of soluble peptide to T-cell
      receptor (TCR) transgenic mice specific for the moth cytochrome c peptide 88-103
      (MCCp). Two weeks after initial peptide treatment, T cells were present in normal
      numbers but were unresponsive to antigen stimulation in vitro. Only bolus
      injections of peptide, either subcutaneous or intravenous, were effective at
      inducing tolerance, while slowly released antigen administered via mini-osmotic
      pump failed to result in anergy. Examination of T cells soon after bolus peptide
      administration revealed that anergy induction was preceded by a transient
      hyperactivation of T cells in vivo. Within 2 hr of peptide treatment, interleukin
      2 was detectable in the plasma of the transgenic mice. Interestingly, only bolus
      injections of peptide led to high levels of T-cell activation, while adjuvant
      emulsified and pump-administered peptide resulted in very low stimulation in
      vivo. When the dose of bolus-injected peptide used for tolerization was titrated,
      the extent of anergy induction directly correlated with the intensity of early T
      cell activation. Indirect measurements of TCR-ligand density on the surface of
      antigen-presenting cells following peptide administration revealed that aqueous
      peptide delivered via bolus injection generated a large number of major
      histocompatibility complex-peptide complexes, while pump-delivered and adjuvant
      emulsified peptide did not. These data suggest that high levels of TCR ligand are
      required for in vivo T-cell hyperactivation and induction of anergy.

PMID- 9767438
TI  - A novel immunosuppressant, FTY720, increases the efficiency of a superantigen
      induced peripheral T-cell deletion whilst inhibiting negative selection in the
      thymus.
AB  - A novel immunosuppressant, FTY720, was generated by chemical modification of ISP
      I, an immunosuppressive compound purified from culture filtrates of Isaria
      sinclairii. FTY720 directly induces apoptotic cell death in lymphocytes, which is
      believed to be the mechanism by which this drug exerts its immunosuppressive
      effect. We examined the effect of FTY720 treatment on antigen-induced apoptotic
      cell death in peripheral T cells and thymocytes. A superantigen, staphylococcus
      enterotoxin B (SEB), induces T-cell antigen receptor (TCR) Vbeta-specific
      apoptotic cell death in mature T cells in vivo. In this well-documented
      experimental system, FTY720 administration significantly enhanced the efficiency
      of superantigen-induced T-cell deletion. We also determined that apoptotic cell
      death with DNA fragmentation induced in T-hybridoma cells after stimulation in
      vitro with anti-TCR antibodies was enhanced in the presence of non-cytolytic
      doses of FTY720. In sharp contrast, negative selection of T cells in the thymus,
      another example of antigen-induced apoptosis, was found to be inhibited by FTY720
      treatment. A rescue effect was observed on clonal deletion in the H-Y-specific
      TCRalpha beta transgenic male thymus. In a chicken egg albumin (OVA)-specific
      TCRalphabeta transgenic system, OVA-induced apoptotic cell death of CD4+CD8+
      thymocytes was also inhibited by FTY720 injection. Thus, FTY720 increased the
      susceptibility of mature T cells to TCR-mediated apoptosis but decreased that of
      immature thymocytes. The results in this report suggest that the potent
      immunosuppressive effect of FTY720 is, in part, a result of the augmentation of
      effects on antigen-induced apoptosis in mature T cells, and that two distinct
      apoptotic cell death pathways are operating in mature and immature T cells.

PMID- 9767440
TI  - Characterization of E-selectin-binding epitopes expressed by skin-homing T cells.
AB  - The glycoprotein counter-receptors for E-selectin borne on skin-homing T cells
      are poorly defined. In this study we have used flow cytometry to investigate the
      surface expression of potential carbohydrate ligands for E-selectin on HUT78, a
      skin-homing cutaneous T-cell lymphoma. These cells possessed high surface
      expression of the KM-93 epitope but not HECA 452 or CSLEX1 epitopes. The KM-93
      antibody also blocked the binding of HUT78 cells to E-selectin. All these
      antibodies are reported to recognize sialyl Lewis X (sLex)-like molecules. Using
      an E-selectin affinity matrix, the main glycoprotein isolated from HUT78 cells
      was a molecular species of 90 000 MW. Other minor species of molecular weights 40
      000, 60 000, 100 000, 120 000 and 200 000 were also identified as potential
      counter-receptors for E-selectin. Four of the purified counter-receptors (90 000,
      100 000, 120 000 and 200 000 MW) stained positive with the KM-93 antibody.
      Immunoblot analysis of these purified glycoproteins established the identity of
      the 90 000 MW glycoprotein as l-selectin. Furthermore, an anti-l-selectin
      antibody inhibited the binding of HUT78 cells to E-selectin, probably by steric
      inhibition of the carbohydrate ligand for E-selectin that is borne on the C-type
      lectin domain of l-selectin. These results suggest that a carbohydrate epitope on
      l-selectin may act as a ligand for E-selectin on skin-homing T cells.

PMID- 9767442
TI  - Autoreactive CD4- CD8- alpha beta T cells to vaccinate adjuvant arthritis.
AB  - Studies suggested that experimental autoimmune diseases can effectively be
      prevented and treated by application of normal autoreactive T cells or
      autoreactive T cells in an attenuated form. In this study, several autoreactive
      CD4- CD8- T-cell clones (A2, A6, and A13 cells) were isolated for the first time
      from the draining lymph nodes of Lewis rats with adjuvant arthritis (AA).
      Surprisingly, intraperitoneal inoculation with A13 cells, but not A2 or A6 cells
      protected rats from AA both clinically and histologically. It was demonstrated
      that A13 cells were CD4- CD8- alpha beta T cells, and showed proliferative
      responses to irradiated syngeneic spleen cells (antigen-presenting cells; APC).
      Interestingly, A13 cells proliferated against concanavalin A (Con A) and
      staphylococcal enterotoxin B (SEB), but did not show any proliferation to
      Mycobacterium tuberculosis (Mt), or its 65 000 MW heat-shock protein (HSP). Rats
      protected from AA by inoculation with A13 cells showed a specific anti-idiotypic
      delayed-type hypersensitivity reaction compared with other autoreactive T cells
      (A2 or A6 cells). These findings demonstrate that AA can be suppressed by
      autoreactive CD4- CD8- alpha beta T cells, and these cells may be used as
      therapeutic agents in experimental autoimmunity.

PMID- 9767441
TI  - A comparison of two techniques for the molecular tracking of specific T-cell
      responses; CD4+ human T-cell clones persist in a stable hierarchy but at a lower
      frequency than clones in the CD8+ population.
AB  - Oligoclonal or clonal T-cell expansions, presumed to be antigen driven, are
      frequently sought and followed for diagnostic and prognostic purposes, as well as
      to understand more about their natural history. Techniques based on conservation
      of T-cell receptor CDR3 length are increasingly widely used, often without
      assessment of sensitivity or specificity. We present a comparative evaluation of
      a novel modified heteroduplex technique and a CDR3-length-based assay. Dilution
      of a known clone in a mixed T-cell population shows that in our hands the
      heteroduplex technique is at least 10-fold more sensitive than the CDR3-length
      based assay. However, even with this level of sensitivity, we do not detect
      clonal expansions in unstimulated CD4+ T cells. This contrasts with the frequent
      detection of CD8+ clones in fresh samples and suggests different mechanisms of
      clonal homeostasis in the two subsets. We show that both techniques detect
      functional expansions after in vitro stimulation with a recall antigen. The
      distinct molecular footprint seen with the heteroduplex technique allows
      reproducible follow up of specific clonal expansions. We have exploited this to
      demonstrate that the repertoire of clones expanded by in vitro tetanus toxoid
      stimulation shows stability within an individual, implying long-term maintenance
      of multiple CD4+ clones.

PMID- 9767443
TI  - Immunodeficiency associated with anorexia nervosa is secondary and improves after
      refeeding.
AB  - Several studies have addressed the question of starvation effects on immune
      function by means of changes in lymphocyte subsets, cytokine induction or
      lymphocyte activation. Anorexia nervosa (AN) patients are severely malnourished
      and contradictory results have been obtained regarding the accompanying
      immunodeficiency, including its assignation as a part of the primary nervous
      disorder. In the present work, an extensive immunological function examination
      was carried out on 40 AN patients who were compared with a control group of 14
      healthy girls. The AN patients were also classified according to their
      nutritional status (by the Body Mass Index: BMI), this being critical for a
      better understanding of these secondary immunodeficiency bases. Moreover, another
      immune system study was performed on five patients after refeeding. Lymphocyte
      subsets and function, cytokine induction and peripheral blood concentrations, and
      innate as well as humoral immunity were evaluated. Deregulation in the cytokine
      network, owing to the interaction of the central nervous (CNS) and immune
      systems, seems to be the initial immune alteration in AN immunodeficiency but it
      has not been disproved that the immunodeficiency is a direct consequence of the
      original psychiatric perturbation. Spontaneous high levels of circulating
      interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) have
      been observed; this is probably one of the causes of the anomalies found in the T
      cell subpopulations (mainly the naive CD4+CD45RA+ reduction and the cytotoxic
      CD8+ increase) and T-cell activation status (mainly the down-regulation of the
      CD2 and CD69 activation pathways). This finally leads to an impairment, not only
      in T-cell function but also in T-cell to B-cell co-operation. The AN specificity
      of these results is confirmed by the fact that these immune alterations improve
      after refeeding and when nutritional status becomes less critical, which also
      suggests that AN immunodeficiency is indeed secondary to malnutrition.

PMID- 9767444
TI  - From sentinel to messenger: an extended phenotypic analysis of the monocyte to
      dendritic cell transition.
AB  - The transitional stages in the relationship between sentinel monocytes and
      messenger dendritic cells that are active in adaptive immunity, are, as yet,
      unclear. To explore these events, 2-hr adherent peripheral blood mononuclear
      cells were used either as monocytes, or cultured for 7 days with granulocyte
      macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) to
      generate dendritic cells, and the phenotypic features and relationship of the two
      cell populations was investigated using an extensive panel of monoclonal
      antibodies (mAbs). The features of the shift from monocyte to dendritic cell were
      also examined by daily phenotyping during the 7-day culture period. Twenty-five
      mAbs, most of which recognized known CD molecules, bound both monocytes and
      dendritic cells equally, whereas 19 mAbs exhibited differential staining. Four
      molecules not previously reported on dendritic cells were documented: CD87, CD98,
      CD147 and CD148. Seven cell-surface molecules (HLA-DQ, CD1a, CD13, CD30, CD43,
      CD63 and CD86) were expressed either at very low levels or not at all on
      monocytes, but had a strikingly increased expression on dendritic cells,
      suggesting a role in antigen presentation. The kinetics of monocyte to dendritic
      cell transition revealed a rapid activation phase within the first 24 hr, with a
      considerable increase in expression of the activation markers HLA-DR, CD13, CD14
      and CD98; this was followed by a down-regulation of CD14 and a more gradual
      development of the other dendritic cell features over the remaining 6 days, with
      steady increases in CD1a, CD18, CD43, CD86, HLA-DR and HLA-DQ. Thus, these
      studies have demonstrated four novel components of the dendritic cell, and have
      documented the dynamic multistep nature of the process whereby an antigen
      presenting dendritic cell phenotype may emerge from a monocyte precursor.

PMID- 9767445
TI  - The regulation of superoxide generation and nitric oxide synthesis by C-reactive
      protein.
AB  - Activated macrophages utilize both reactive oxygen intermediates and reactive
      oxynitrogen intermediates for defence against microbes. However, simultaneous
      generation of superoxide (O- 2;) and nitric oxide (NO) could be harmful to host
      cells due to the production of peroxynitrite, nitrogen dioxide and hydroxyl
      radicals. Therefore, the regulation of the production of these molecules is
      critical to host survival. During periods of inflammation or infection, the level
      of serum C-reactive protein (CRP) increases in many species. Human and rat CRP
      have been shown to bind and interact with phagocytic cells. Since many of the
      interactions of CRP involve the binding to the phosphocholine ligand, we studied
      the role of CRP in O- 2; and NO generation through the modulation of
      phosphatidylcholine (PC) metabolism in macrophages. This study has shown that,
      while rat CRP inhibited phorbol myristate acetate- (PMA) induced release of O- 2;
      by rat macrophages, CRP-treated macrophages released NO in a time- and dose
      dependent manner. CRP increased inducible nitric oxide synthase (iNOS) enzyme as
      well as iNOS mRNA levels in rat macrophages. Tricyclodecan-9-yl-xanthogenate
      (D609), an inhibitor to PC phospholipase C (PC-PLC), suppressed iNOS induction
      but enhanced PMA-induced release of O- 2;. These data indicate that an increased
      level of CRP during periods of inflammation may result in differential regulation
      of macrophage NADPH oxidase and iNOS activity. Increased hepatic synthesis of CRP
      may contribute to the mechanism by which phagocytic cells avoid simultaneous O-
      2; and NO synthesis, and this could possibly be mediated through the regulation
      of PC-PLC.

PMID- 9767446
TI  - Fas ligand (FasL, CD95L, APO-1L) expression in murine mast cells.
AB  - Fas ligand (FasL, CD95L, Apo-1L), a type II membrane protein belonging to the
      tumour necrosis factor family, induces apoptosis in Fas-bearing cells. As murine
      mast cells have been shown to express Fas antigen, we hypothesized that mast
      cells might also express FasL. To explore this possibility, we first demonstrated
      FasL mRNA in mast cells by reverse transcription-polymerase chain reaction and
      FasL protein by immunoblot analysis. FasL protein was shown to be exclusively
      located within the cell by flow cytometry. In agreement with this observation,
      bone marrow cultured mast cells were unable to kill Jurkat T cells. Our results
      demonstrate that FasL is expressed in murine mast cells and suggest that this
      murine mast cell FasL is not lytic, owing to the intracellular localization.

PMID- 9767447
TI  - Involvement of protein kinase C-delta in CD28-triggered cytotoxicity mediated by
      a human leukaemic cell line YT.
AB  - Ligation of CD28 molecules expressed on the surface of human leukaemic natural
      killer-like YT cells triggers intracellular signals leading to cytolysis of
      target cells expressing CD80 or CD86 molecules. Known intracellular events
      include tyrosine phosphorylation, activation of phosphatidylinositol 3-kinase,
      and protein kinase C (PKC). In this study, we report that PKC-delta isoenzyme
      activity is required for CD28-triggered cytotoxicity mediated by YT cells and we
      also demonstrate that one of the primary targets of bryostatin 1, a modulator of
      PKC activity, is PKC-delta. Treatment of YT cells with bryostatin 1 caused
      degradation of PKC-delta, but not other PKC isoenzymes, and completely blocked
      the cytolytic activity of YT cells. In addition, PKC-delta-specific antibody
      introduced into YT cells by electroporation inhibited partially the YT cell
      mediated cytotoxicity of B-lymphoblastoid cell line JY. This effect was specific,
      since addition of anti-PKC-delta antibody-blocking peptide in combination with
      anti-PKC-delta antibody to YT cells for electroporation, neutralized the effect
      of this antibody. These results demonstrate that YT cell cytolytic activity is
      dependent on PKC-delta, which is selectively down-regulated by bryostatin 1.

PMID- 9767448
TI  - Localization in situ of costimulatory molecules and cytokines in B-cell non
      Hodgkin's lymphoma.
AB  - Costimulatory molecules are essential in cognate interactions between T and B
      lymphocytes. To study the prerequisites of functional interactions between
      malignant B cells and intermingled T cells in B-cell non-Hodgkin's lymphomas (B
      NHL), we examined the expression of CD40, CD80 and CD86 and their ligands CD40
      ligand (CD40L, CD154), CD28 and CTLA4 (CD152) using immunohistochemistry and
      confocal laser scanning microscopy. Almost all mucosa-associated lymphoid tissue
      (MALT) NHL were positive for CD40 and CD80 and in nine out of 14 cases were
      positive for CD86. The majority of follicle centre cell lymphomas (FCCL)
      expressed CD40, but were heterogeneous in their expression of CD80 and CD86. Most
      diffuse large cell lymphomas (DLCL) were CD80+, but lacked expression of CD86.
      These patterns reflect the differences in phenotype of normal marginal-zone B
      cells (as counterparts of MALT NHL) and germinal centre cells (as counterparts of
      FCCL and DLCL). Counter-receptors on T cells were detectable in 13 of 14 MALT
      NHL, 12 of 16 FCCL but only occasionally in DLCL (three of 12 cases). A subgroup
      of FCCL was identified with T-cell expression of CD40L, CD28 and CTLA4
      simultaneously with strong expression of CD40 and CD86 on the tumour B cells.
      These results indicate that MALT NHL and a subset of FCCL are most optimally
      equipped for functional interactions with T cells. This may be supported by the
      demonstration of cytokine production - mainly in T cells - in MALT NHL
      [interleukin-2 (IL-2), interferon-gamma (IFN-gamma), IL-10] and FCCL (IL-2, IFN
      gamma) and to a lesser extent in DLCL.

PMID- 9767449
TI  - Serum levels, ontogeny and heritability of chicken mannan-binding lectin (MBL).
AB  - Mannan-binding lectin (MBL) is a serum lectin found in mammals and recently also
      in birds. It is thought to play an important role in the innate immune defence
      through binding to surface carbohydrates on micro-organisms followed by
      complement activation via the MBL pathway. This results in opsonization or direct
      complement-mediated killing. To gain further knowledge about the physiology and
      function of the protein, we developed an enzyme-linked immunosorbent assay for
      chicken MBL and used this to investigate the level of MBL in different chicken
      strains during embryogenesis, early and adult life. The MBL concentrations in 308
      chickens, representing 14 different strains, showed a non-Gaussian, unimodal
      distribution profile with a mean concentration of 5.8 micrograms/ml (range 0.4
      37.8 micrograms/ml). No difference between the strains could be demonstrated and
      no chickens were found deficient in MBL. Ontogenetic studies showed that MBL is
      already detectable in embryos at a gestational age of 10 days (11 days before
      hatching). At hatching, the level is comparable to the level found in adult
      chickens. This level is fairly stable during the first weeks of life, but a
      deficiency state develops at 4 weeks of age, whereafter the level is normalized
      again at 5 weeks of age. Chickens with relatively low or high MBL levels were
      bred with cockerels having similar MBL levels and this resulted in F1 generations
      with significantly different MBL levels, suggesting that the protein level is
      genetically influenced.

PMID- 9767450
TI  - Disease-protected major histocompatibility complex Ea-transgenic non-obese
      diabetic (NOD) mice show interleukin-4 production not seen in susceptible Ea
      transgenic and non-transgenic NOD mice.
AB  - The non-obese diabetic (NOD) mouse is an animal model for insulin-dependent
      diabetes that has many similarities to the human disease. NOD mice transgenic for
      the Ea gene, allowing expression of the E molecule, are protected from diabetes
      and rarely develop insulitis. An Ea transgene mutated in the promoter region,
      (DeltaY) lacks E expression on most B cells, thymic medullary epithelium and
      primary antigen-presenting cells, and confers no protection whatsoever. We have
      used these transgenic NOD mice, together with non-transgenic NOD mice, to study
      the correlation of E expression and production of interleukin-4 (IL-4) and
      interferon-gamma (IFN-gamma). We show that protected E-transgenic NOD mice have
      elevated levels of IL-4 compared with non-transgenic mice, both in the thymus and
      in the periphery. However, susceptible DeltaY-transgenic mice have elevated
      thymic IL-4 levels, but express almost as little IL-4 as non-transgenic NOD mice
      in the periphery. This drop in peripheral IL-4 production seen in DeltaY
      transgenic mice thus correlates with the decreased E expression in the periphery
      of DeltaY-transgenic NOD mice. In contrast, there were no differences in IFN
      gamma production between the three NOD lines. We suggest that Ea-transgenic NOD
      mice have E-selected regulatory T cells producing IL-4, which are subsequently
      activated by E-expressing primary antigen-presenting cells in the periphery. This
      activation would then be instrumental for the E-mediated protection from disease
      in NOD mice. Such a process would explain the total absence of protection in
      DeltaY-transgenic NOD mice, despite their widespread E expression.

PMID- 9767451
TI  - Characterization and specificity of B-cell responses in lupus induced by
      Mycobacterium bovis in NOD/Lt mice.
AB  - A single dose of pasteurized Mycobacterium bovis administered intravenously to
      prediabetic non-obese diabetic (NOD) mice prevented the onset of type 1 diabetes
      but precipitated a systemic 'autoimmune rheumatic disease' (ARD) similar to
      systemic lupus erythematosus. This syndrome was characterized by haemolytic
      anaemia, anti-dsDNA and anti-Smith antigen (Sm) antinuclear autoantibodies,
      increased severity of sialadenitis and glomerular immune complex deposition.
      Here, we examine the specificity of the autoantibody responses in M. bovis
      treated NOD mice. Large amounts of antibody were detected to the
      Sm/ribonucleoprotein (RNP) complex, of which the 28 000 MW polypeptide appeared
      to be immunodominant. The IgG subclass involved in the anti-Sm response was
      primarily IgG2a. Antibodies against dsDNA were also detected, but the subclass of
      this response was mixed, with IgG2a and IgG2b being present in equal amounts.
      Together, these findings argue against a role for immune deviation towards T
      helper type 2 (Th2) responses in pathogenesis of the disease. The anti-dsDNA and
      anti-Sm reactivities were not mediated by polyreactive antibodies since neither
      antigen could cross-compete plasma antibody binding to the other in competitive
      enzyme-linked immunosorbent assay. The role of polyclonal B-cell activation was
      examined by measuring total gamma-globulin as well as IgG reactive with other
      nuclear antigens including Ro60, Ro52 and La, which although not a major
      component of the autoantibody responses in these mice, did show small but
      significant increases following immunization with M. bovis. Thus polyclonal
      stimulation, while likely to be occurring, was not directly responsible for
      production of anti-Sm antibodies.

PMID- 9767452
TI  - T-cell receptor Vbeta gene expression in experimental lupus nephritis.
AB  - A limited T-cell receptor (TCR) Vbeta repertoire employed by autoreactive T cells
      may be related to the development and course of autoimmune diseases. Vbeta
      repertoire skewing has been observed not only in man, but also in animal models
      of several human autoimmune diseases, such as MRL-lpr mice, which spontaneously
      develop a systemic lupus erythematosus (SLE)-like disease. Murine chronic graft
      versus-host disease (GVHD) is an inducible model for SLE, involving direct
      interaction between donor T cells and recipient B cells. It is not known whether
      Vbeta-specific T-cell subsets are pathogenically involved in this model.
      Retroviral superantigens such as Mls-1 are known to have a profound impact on the
      TCR Vbeta repertoire in mice. Restriction of the peripheral TCR repertoire may
      result from intrathymic expression of Mls-1, which causes deletion of T cells
      expressing Vbeta6, -7, -8.1, or -9. Mls-1 incompatibility between donor and
      recipient can be used to determine the involvement of these TCR Vbeta families in
      GVHD. In the present study we induced GVHD in several strain combinations to
      investigate TCR Vbeta gene expression during GVHD, and the effect of Mls-1
      incompatibility on the TCR Vbeta repertoire. TCR Vbeta gene expression was
      determined using an RNase protection assay. Our results indicate that T cells
      expressing the Vbeta2 or Vbeta16 chain play an important pathogenetic role, while
      T cells bearing the Vbeta1 or Vbeta6 chain may be related to self-limitation of
      the lupus-like disease in this model.

PMID- 9767453
TI  - Amidolytic and peptidolytic activities of immunoglobulin G present in sera from
      patients with rheumatoid arthritis, Sjogren's syndrome and systemic lupus
      erythematosus.
AB  - Polyclonal immunoglobulin G (IgG) from healthy subjects was found to be capable
      of hydrolyzing carbobenzoxy-Val-Gly-Arg-p-nitroanilide (a synthetic chromogenic
      substrate for trypsin) and D-Pro-Phe-Arg-p-nitroanilide (a substrate for plasma
      kallikrein). Statistically significant elevation of activity against the former
      substrate was found in patients with rheumatoid arthritis (RA), but not in
      patients with Sjogren's syndrome (SjS) or systemic lupus erythematosus (SLE). On
      the other hand, IgG samples from the patients with these three autoimmune
      diseases showed reduced activity against d-Pro-Phe-Arg methylcoumarinamide,
      although the differences were not statistically significant. Preliminary studies
      have shown that two out of three IgG samples from RA patients exhibited the
      activity of cleaving a pentapeptide, Gln-Arg-Arg-Ala-Ala, whereas virtually no
      cleavage of the same peptide was observed with IgG from healthy controls or from
      patients with SjS or SLE.

PMID- 9767454
TI  - An anti-inflammatory role for interleukin-11 in established murine collagen
      induced arthritis.
AB  - Interleukin-11 (IL-11) is a cytokine belonging to the IL-6 family which has both
      pro- and anti-inflammatory potential. Like IL-6 it can diminish tumour necrosis
      factor-alpha and IL-1 production, and augment immunoglobulin synthesis. We have
      explored the immunomodulatory effects of IL-11 treatment in mice in a model of
      inflammatory autoimmune joint disease, collagen-induced arthritis (CIA).
      Recombinant human IL-11 was administered at various doses to DBA/1 mice after the
      onset of CIA. IL-11 treatment caused a significant reduction in the clinical
      severity of established CIA, which was associated with protection from joint
      damage, as assessed by histology. Although there was a suggestion at high doses
      of IL-11 that the anticollagen type II (CII) response may have been augmented,
      there was no statistically significant effect of IL-11 treatment on anti-CII
      antibody levels. Similarly, the acute-phase reactant serum amyloid P was only
      elevated in mice receiving very high doses (50-100 microgram/day) of IL-11.
      Endogenous IL-11 was abundantly produced in synovial membrane cultures derived
      from CII-immunized mice with active disease, suggesting that, as in rheumatoid
      arthritis, this cytokine is spontaneously produced in the inflammatory response
      in CIA. The results presented here demonstrate an anti-arthritic immunoregulatory
      role for IL-11 in murine CIA, and suggest that IL-11 is a candidate therapeutic
      molecule for human inflammatory arthritic diseases.

PMID- 9767455
TI  - CD4+ T-cell-mediated cytotoxicity against staphylococcal enterotoxin B-pulsed
      synovial cells.
AB  - Apoptosis of synovial cells in rheumatoid arthritis (RA) synovium determined in
      vivo is suggested to counteract the overgrowth of synovium. Immunohistological
      examination has revealed the infiltration of activated CD4+ T cells, which
      express Fas ligand (FasL), in RA synovium. The presence of a putative antigen
      (Ag) of autoimmune disorders in a target organ may induce the activation of
      specific T cells in the inflammatory region such as RA synovium. We examined the
      possible role of CD4+ T cells activated by synovial cells in a staphylococcal
      enterotoxin B (SEB)-dependent manner, inducing synovial cell apoptosis. Synovial
      cells were cultured with or without interferon-gamma (IFN-gamma) and further
      incubated with CD4+ T cells in the presence of SEB. After the cocultivation, both
      the cytotoxicity and FasL expression of CD4+ T cells were investigated.
      Constitutive Fas expression was detected on both unstimulated and IFN-gamma
      stimulated synovial cells. CD4+ T cells did not kill SEB-pulsed unstimulated
      synovial cells efficiently. In contrast, when CD4+ T cells were incubated with
      IFN-gamma-stimulated synovial cells with SEB whose human leucocyte antigen (HLA)
      DR and -DQ expression was markedly induced, significant cytotoxicity by these
      cells against synovial cells was detected. The addition of anti-HLA-DR and -DQ
      monoclonal antibodies (mAbs) or human Fas chimeric protein (hFas-Fc) reduced this
      cytotoxicity. FasL expression of CD4+ T cells cocultured with IFN-gamma
      stimulated synovial cells with SEB was significantly induced. Furthermore, the
      addition of mAbs against CD54, CD58 and CD106 inhibited both the cytotoxicity and
      FasL expression of CD4+ T cells induced by IFN-gamma-stimulated synovial cells in
      the presence of SEB, indicating the importance of costimulatory molecules on
      synovial cells in activating CD4+ T cells. Our results suggest that CD4+ T cells
      are activated by synovial cells by an SEB-dependent manner and express FasL,
      inducing Fas-mediated apoptosis of the latter cells. These phenomena may regulate
      the overgrowth of synovial cells in RA synovium.

PMID- 9767456
TI  - Splenic B cells are required for tolerogenic antigen presentation in the
      induction of anterior chamber-associated immune deviation (ACAID).
AB  - Ocular immune privilege is the result of a number of protective mechanisms,
      including a specialized immune response to antigen encountered in the anterior
      chamber of the eye. Anterior chamber-associated immune deviation, or ACAID, is
      characterized by the antigen-specific, selective down-regulation of systemic cell
      mediated and humoral immune responses. One current hypothesis of the initiation
      of ACAID predicts that ocular APC process antigen and then migrate out of the eye
      and to the spleen where various regulatory T-cell populations are generated. A
      novel in vitro model of the ACAID spleen was developed to study the cells
      involved in the generation of suppressed T-cell immunity. ACAID APC co-cultured
      with whole splenocytes or splenic B and T cells induced efferent suppressors of
      delayed-type hypersensitivity (DTH). However, ACAID APC co-cultured with splenic
      T cells did not generate efferent suppressors of DTH. The requirement for B cells
      was confirmed with B-cell knockout mice. ACAID APC co-cultured with splenocytes
      from B-cell knockout mice did not induce efferent suppressors of DTH. Moreover,
      ACAID could not be induced in B-cell knockout mice in vivo. The reconstitution of
      B-cell knockout mice with wild-type B cells restored ACAID. In summary, these
      data confirm the role for B cells in the splenic phase of ACAID. A putative
      mechanism predicts that ACAID APC release antigenic peptides to B cells in the
      spleen. B cells then present antigen in a tolerogenic manner leading to the
      generation of regulatory T cells.

PMID- 9767457
TI  - Lymphotactin: a key regulator of lymphocyte trafficking during acute graft
      rejection.
AB  - The attraction of leucocytes to allografts is essential for rejection. The
      process is controlled by chemokines. In order to clarify the role of lymphotactin
      (a cytokine that represents a novel branch of the chemokine superfamily) in
      regulating leucocyte trafficking during graft rejection, we used rat renal
      transplantation models to examine its gene expression and the distribution of
      lymphotactin-expressing cells in renal grafts. Lymphotactin mRNA was upregulated
      strongly in acutely rejecting renal allografts. The mRNA was undetectable in
      isografts, chronically rejecting renal allografts or normal kidney. Once
      lymphotactin was expressed, large numbers of infiltrating lymphocytes were seen.
      Moreover extended studies demonstrated that in cultured rat spleen cells the
      expression of lymphotactin mRNA was markedly induced by phytohaemagglutinin (PHA)
      or phorbol myristate acetate (PMA), and such induction was inhibited by the
      immunosuppressive drugs FK506 and cyclosporin. Collectively, these observations
      provide new evidence demonstrating that lymphotactin is a key regulator of
      lymphocyte motility and adhesiveness during acute allograft rejection. FK506 and
      cyclosporin inhibition of lymphotactin expression is likely to represent an
      important molecular mechanism of the action of the drugs.

PMID- 9767459
TI  - Analysis of T cells recruited during delayed-type hypersensitivity to purified
      protein derivative (PPD) versus challenge with tuberculosis infection.
AB  - The delayed-type hypersensitivity (DTH) to purified protein derivative (PPD) test
      has been used to infer about protective immunity to Mycobacterium tuberculosis
      and to diagnose tuberculosis. We showed that in memory tuberculosis-immune mice
      both DTH to PPD and resistance to M. tuberculosis could be effectively elicited
      in the footpad and both reactions led to the accumulation of reactive T cells in
      the regional lymph nodes with a CD4+ phenotype and characterized by the secretion
      of high levels of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) and no IL
      4. By adoptive transfer into nude mice of highly purified CD4+ T cells harvested
      during the recall of protective immunity it was confirmed that this population
      mediated both manifestations. However, the specificity of the T cells recruited
      during these processes were found to differ markedly; T cells involved in
      protection to a challenge with live tuberculosis bacilli recognized predominantly
      low-mass culture filtrate antigens below 15 000 MW, while cells recruited during
      DTH to PPD were directed to molecular mass fractions between 15 000 and 31 000.
      Using single purified antigens we showed that the latter cells recognized the
      secreted mycobacterial protein Ag85B and the heat-shock proteins, DnaK and GroEL.
      Protective T cells, in contrast, were characterized by a very high frequency of T
      cells directed to the ESAT-6 peptide 1-20.

PMID- 9767458
TI  - Direct and rapid induction of migration in human CD4+ T lymphocytes within three
      dimensional collagen matrices mediated by signalling via CD3 and/or CD2.
AB  - Specific activation of T cells requires stable cell-cell interaction; however,
      little is known how the transition from a previously motile state into a sessile
      state following activation is achieved. We investigated the direct effect of T
      cell receptor (TCR)/CD3 complex engagement and/or stimulation of the accessory
      molecule CD2 on the locomotion of peripheral human T cells within three
      dimensional (3-D) collagen lattices. Simultaneous engagement of CD3 and CD2 very
      potently stimulated T-cell migration, resulting in the recruitment of previously
      sessile cells (about 24% of the total population was additionally recruited) as
      well as an increase in the mean duration of active locomotion. This induction of
      migration was accompanied by an increased tyrosine phosphorylation of a 125 000
      MW substrate corresponding to the focal adhesion kinase. Using confocal laser
      scanning microscopy we detected antibody-induced receptor capping into the uropod
      of migrating T cells whereas untreated control cells displayed an even
      distribution of CD3 and CD2 on the cell surface. Less pronounced induction of
      locomotion was achieved following triggering of CD3 or CD2 alone. Thus, in 3-D
      collagen lattices specific T-cell activation did not lead to cessation of
      cellular migration but rather induced cytoskeletal activity that ultimately
      resulted in vigorous locomotory activity.

PMID- 9767460
TI  - T cell- and perforin-dependent depletion of B cells in vivo by staphylococcal
      enterotoxin A.
AB  - Bacterial superantigens bind to major histocompatibility complex (MHC) class II
      and subsequently activate both CD4+ and CD8+ T lymphocytes expressing certain T
      cell receptor (TCR)-Vbeta chains. In response to superantigen exposure these
      subsets proliferate, produce large amounts of proinflammatory cytokines and in
      addition CD8+ cytotoxic T lymphocytes (CTL) are induced. Previous studies in
      vitro have shown that these CTL effectively lyse MHC class II-expressing cells
      presenting the proper superantigen. However, it is unknown whether superantigens
      induce a similar response towards MHC class II+ antigen-presenting cells in vivo.
      In this study we demonstrate that administration of repeated injections of the
      superantigen staphylococcal enterotoxin A (SEA) to TCR-Vbeta3 transgenic mice
      results in a loss of MHC class II-expressing cells in the spleen. Analysis of
      different MHC class II+ subsets revealed a selective depletion of CD19+ B cells,
      while F4/80+ macrophages increased in number. Depletion of T cells with anti-CD4
      or anti-CD8 monoclonal antibody indicated that CD8+ T cells were crucial for SEA
      induced cytotoxicity in vivo. Repeated injections of SEA to perforin-deficient
      mice resulted in significantly less B-cell depletion compared with control mice.
      This suggests that superantigen-activated CD8+ T cells lyse MHC class II+ antigen
      presenting cells in a perforin-dependent manner in vivo. It is suggested that
      this represents a novel bacterial immune escape mechanism, which may particularly
      impair local humoral immune responses.

PMID- 9767461
TI  - Interleukin-1beta partially alleviates cyclosporin A-induced suppression of IgG1
      isotype response to thyroglobulin in BALB/c mice in vivo.
AB  - Cyclosporin A (CsA) at 120 mg/kg body weight when injected subcutaneously into
      BALB/c mice along with thyroglobulin emulsified in incomplete Freund's adjuvant
      (IFA) was found to suppress antigen-specific IgG titre by 86%. Isotyping revealed
      that both IgG1 and IgG2a titres were suppressed by 87% and 57%, respectively. But
      under identical conditions when complete Freund's adjuvant (CFA) was used, the
      suppression of antigen-specific IgG, IgG1 and IgG2a titres was 50%, 51% and 55%,
      respectively. Injection of anti-IL-1beta-neutralizing hamster monoclonal
      antibodies along with thyroglobulin and CsA emulsified in CFA increased the
      suppression of antigen-specific IgG titre. Under such conditions the IgG1 titre
      was suppressed more than the IgG2a titre. Recombinant human interleukin-1
      receptor antagonist (rhuIL-1ra) also enhanced the suppression caused by CsA in
      the presence of CFA but control hamster immunoglobulin had no such effect.
      Recombinant human IL-1beta, when administered along with thyroglobulin and CsA
      emulsified in IFA, alleviated the suppression of antigen-specific IgG titre and
      the IgG1 titre was alleviated more than the IgG2a titre. Under identical
      conditions, rhuIL-1ra did not alleviate CsA-induced suppression. Lymphocytes from
      the lymph nodes of thyroglobulin-sensitized BALB/c mice when stimulated in vitro
      by thyroglobulin in the presence of CsA, secreted very little interferon-gamma
      (IFN-gamma) and IL-4, but on addition of an optimal dose of rhuIL-1beta, IFN
      gamma and IL-4 secretion was partially restored.

PMID- 9767462
TI  - Lack of SC/pIgR-mediated epithelial transport of a human polymeric IgA devoid of
      J chain: in vitro and in vivo studies.
AB  - Three human polymeric IgA (pIgA) myeloma proteins of tetrameric size were
      compared for their J-chain content, their in vitro secretory component (SC)
      binding ability, and their capacity to be transcytosed by polymeric
      immunoglobulin receptor (pIgR)-expressing epithelial cells in vitro and rat
      hepatocytes in vivo. One of the three pIgA preparations, pIgA-L, was shown to
      lack J chain and was unable to combine with purified free human and rat SC,
      whereas pIgA-G and pIgA-C contained J chain and combined readily with SC.
      Furthermore, pIgA-L was not transferred into rat bile after intravenous
      injection, and was hardly transported apically by polarized Madin-Darbey canine
      kidney cell monolayers expressing the human pIgR, whereas pIgA-G and pIgA-C were
      efficiently transported in both test systems. Together with our recent
      demonstration that antibodies to human J chain block the SC/pIgR-mediated
      epithelial transport of pIgA, these data unanimously confirm the proposed key
      role of J chain in the epithelial transport of polymeric immunoglobulins into
      exocrine secretions.

PMID- 9767464
TI  - Inhibition of sCD23 and immunoglobulin E release from human B cells by a
      metalloproteinase inhibitor, GI 129471.
AB  - Soluble CD23 (sCD23) has been proposed to play an important role in the up
      regulation of immunoglobulin E (IgE) synthesis. Production of sCD23 is dependent
      on the proteolytic cleavage of membrane CD23, but the protease(s) involved in
      this process remain unknown. Preliminary data, obtained by testing a panel of
      protease inhibitors, suggested that this enzyme may be a zinc-dependent
      metalloproteinase. Therefore, we investigated the effect of a standard
      hydroxamate-type Zn2+ metalloproteinase inhibitor (GI 129471) on both sCD23 and
      IgE release from human tonsillar B cells, stimulated with interleukin-4 (IL-4)
      and anti-CD40. Incubation of cells for 3 days with GI 129471 inhibited the
      production of sCD23 with an IC50 of 602 nm+/-3 nm (n=3), but by 14 days the
      activity of the compound against sCD23 had decreased by greater than threefold
      (IC50 2+/-0.26 microM; n=3). On the other hand, GI 129471 caused a potent
      inhibition of IgE production, with no apparent loss of activity over the culture
      period (14 days: IC50 250 nm+/-72 nm; n=3). Time-course studies showed that,
      despite loss of activity against sCD23, inhibition of sCD23 production early in
      the culture was able to cause a potent and long-lasting inhibitory effect on IgE.
      Furthermore, we also showed that the activity of GI 129471 is selective for IgE,
      as no effect was seen on immunoglobulin G1 (IgG1) or IgG4 production at test
      concentrations as high as 10 microM. These results support the hypothesis that
      metalloproteinases may be involved in the proteolytic cleavage of CD23 and
      subsequent regulation of IgE synthesis. Inhibition of the protease(s) responsible
      for such cleavage may be of value in the treatment of allergic disease.

PMID- 9767463
TI  - Eosinophilia, IgE production, and cytokine production by lung T cells in surface
      CD4-deficient mutant mice infected with Toxocara canis.
AB  - Mutant mice deficient in CD4+ T cells and their normal and heterozygous
      littermates were infected with Toxocara canis, and compared for eosinophilia,
      total and Toxocara-specific immunoglobulin E (IgE) production, and in vitro
      cytokine production by lung cells. The numbers of eosinophils in the peripheral
      blood of normal and heterozygous mice peaked on days 10 and 21, although mutant
      mice showed eosinophilia with a peak on day 10. This indicates that the first
      peak on day 10 is CD4 independent and the second peak is CD4 dependent. Before
      infection, the levels of total IgE had no significant difference among the three
      groups of mice. Total and Toxocara-specific IgE in all genotypes of mice
      increased after infection, and was the highest in normal mice and the lowest in
      mutant mice. In vitro production of interleukin (IL)-5 and IL-4 by total lung
      cells was the highest in normal mice and the lowest in mutant mice. CD4+ and CD4-
      CD8- T lymphocytes, but not CD8+ T lymphocytes produced IL-5 and IL-4 when
      incubated with anti-CD3 monoclonal antibody (mAb) and lung-adherent cells. These
      results indicated that IL-5 and IL-4 were produced mainly by CD4+ cells and
      partly by CD4- CD8- cells, but not by CD8+ cells. In addition, cytokine
      production by CD4+ cells was affected by the number of CD4 molecules on their
      surface.

PMID- 9767465
TI  - Role of mast cells and monoamines in the thrombocytopaenia and mortality elicited
      by tumour necrosis factor in mice.
AB  - We explored the thrombocytopaenia elicited by the i.v. injection of mouse
      recombinant tumour necrosis factor (TNF) in mice. Injection of 10 micrograms of
      TNF led to a thrombocytopaenia (evident after 0.5 hr) which was caused by
      decreased platelet survival, as seen by the injection of labelled platelets. TNF
      induced thrombocytopaenia was not prevented by heparin, nor by depletion of
      either fibrinogen or C'. TNF-induced thrombocytopaenia was markedly attenuated in
      mice treated with reserpine, an agent that depletes monoamines from mast cells
      and other cells, and in the mast-cell-deficient WWv mice. In vitro, TNF elicited
      a modest release of monoamine from peritoneal mast cells and from a mast cell
      line. When mice are injected with 3H-serotonin (3H-5HT) before TNF, TNF injection
      increased the plasma 3H-5HT content 1 hr later, modifications absent in reserpine
      pretreated or mast-cell-deficient mice. 3H-5HT content of the small intestine was
      markedly depleted in TNF-injected mice, suggesting that this organ is the source
      of the plasma 3H-5HT. Drop in body temperature and mortality induced by TNF were
      also attenuated in mast-cell-deficient, and in reserpine pretreated mice. These
      results indicate that TNF can induce a release of monoamines from mast cells,
      mainly from those of the small intestine, a process that contributes to TNF
      induced thrombocytopaenia and mortality.

PMID- 9767466
TI  - Rat NKR-P1+ CD3+ T cells: selective proliferation in interleukin-2, diverse T
      cell-receptor-Vbeta repertoire and polarized interferon-gamma expression.
AB  - Cells expressing markers of both natural killer and T lymphocytes (NK T cells) in
      humans and mice express a restricted T-cell receptor (TCR) repertoire, are of CD4
      CD8- or CD4+ CD8- phenotype, and upon anti-CD3 stimulation secrete large amounts
      of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma). NK T cells may be the
      primary source of IL-4-promoting T helper type 2 (Th2) responses and/or they
      might be involved in regulating the balance between Th1- and Th2-type immune
      responses, and may consequently affect susceptibility to autoimmune diseases
      associated with a skewed Th phenotype. We show that rat NK T cells selectively
      proliferate to IL-2, and use this fact to analyse cytokine production by NK T
      cells in two rat strains differentially susceptible to Th1- or Th2-type
      autoimmune diseases. Analysis by reverse transcription-polymerase chain reaction
      revealed that, in contrast to mouse, rat NK T cells secrete exclusively IFN-gamma
      and not IL-4 after anti-CD3 stimulation, and use a wider TCR-Vbeta repertoire,
      suggesting that rat NK T cells are not essential for the development of Th2-type
      CD4+ T-cell responses.

PMID- 9767467
TI  - Modulation of Ly49A receptors on mature cells to changes in major
      histocompatibility complex class I molecules.
AB  - The expression of murine Ly49 receptors on natural killer (NK) cells and NK1.1+ T
      cells is believed to prevent these cells from responding against normal self
      tissues. In this report we investigated whether the expression level of Ly49A was
      fixed on mature cells or if it could be adapted as the major histocompatibility
      complex (MHC) class I environment changed in vivo. By transferring peripheral T
      cells from Ly49A transgenic mice into BALB/c nude/nude and B6 nude/nude mice, we
      demonstrated that mature cells modulate their Ly49A receptor expression relative
      to the in vivo MHC class I environment. These results indicated that the
      expression of the inhibitory Ly49A receptor is not permanently fixed during a
      maturation and/or education process but rather is adapted to MHC class I changes
      on the surrounding cells.

PMID- 9767468
TI  - A long-lasting interferon-gamma response is induced to a single inoculation of
      antigen-pulsed dendritic cells.
AB  - Vaccines against infectious organisms must produce not only long-lasting immunity
      but also the appropriate immune response to clear the infection. Obligate
      intracellular parasites, such as mycobacteria, require a predominantly cell
      mediated immune response rather than antibody. Presentation of antigen by
      dendritic cells (DC) has been associated with the development of strong cell
      mediated responses generating the production of interferon-gamma (IFN-gamma).
      This cytokine has an essential role in the elimination of mycobacteria.
      Therefore, we investigated both the duration and the nature of the immune
      response after priming with DC pulsed with mycobacterial antigen and compared
      this with priming using a conventional adjuvant. We used two strains of mice:
      C57BL/6, which inherently produces a T-helper 1 (Th1)-type response to
      mycobacterial antigen, and BALB/c, which does not. DC-enriched cell suspensions,
      purified DC or cultured bone marrow cells resembling DC (BMAPC) were prepared,
      pulsed overnight with PPD and injected intravenously (i.v.) into naive mice. Six
      and 12 weeks later, splenic T lymphocytes from these mice were challenged in
      vitro with antigen and their proliferative response and cytokine production was
      determined. Significant antigen-specific proliferation was observed in all assays
      on rechallenge with antigen in vitro 6 and 12 weeks after the initial priming
      with DC. IFN-gamma was detected in both strains but was only antigen specific in
      the C57BL/6 strain. Purified protein derivative (PPD)-pulsed BMAPC generated
      similar responses 6 weeks after priming. Thus, long-term T-lymphocyte responses
      and the production of IFN-gamma can be generated using a single inoculation of
      PPD-pulsed DC.

PMID- 9767470
TI  - NADPH diaphorase-positive dendritic profiles in rat thymus are discrete from
      autofluorescent cells, immunoreactive for inducible nitric oxide synthase, and
      show strain-specific abundance differences.
AB  - Predisposition to autoimmune disorder in Lewis rats has been associated with
      abnormal hypothalamic regulation of circulating steroids, leading to inadequate
      suppression of T helper 1 (Th1) cell-mediated inflammatory reactions. In
      addition, autoimmune syndromes can be triggered within formerly resistant
      animals, following damage to the negative selection process of the thymus. A
      contribution to the autoimmune-susceptible phenotype may therefore derive from
      the status of thymic tolerance. One mechanism of intrathymic negative selection
      may involve nitric oxide. Because inducible nitric oxide synthase (iNOS) is known
      to be inhibitable by steroids, its expression might be different within strains
      having neuroendocrine disturbance. We report on a study to compare intrathymic
      iNOS expression in autoimmune-prone Lewis rats with other resistant strains.
      Interdigitating cells (IDC), darkly stained for diaphorase, were confirmed as
      immunoreactive for iNOS. They were located towards the medullary side of an
      accumulation of unstained, but autofluorescent cells (presumed to be macrophages)
      that circumscribes the corticomedullary zone. The role of iNOS+ IDC in the
      apoptotic deletion of T cells has been suggested by other studies. Despite the
      blunted steroidal condition reported for Lewis, nitrergic cell abundance was
      shown, by quantitative analysis of histochemical stain, to be on average
      approximately twofold lower compared with resistant strains (Fischer and Sprague
      Dawley). This trend was evident in males and females, and confirmed by
      independent observers. We hypothesize that an intrathymic, iNOS-dependent
      mechanism may be important for the suppression of potentially autoreactive T-cell
      clones.

PMID- 9767472
TI  - Low-cost image-capture system for a scanning electron microscope.
AB  - We describe a PC-based active-capture system for recording digital images from a
      scanning electron microscope. The system is based on a National Instruments data
      acquisition board and a Pentium computer, controlled by software that we have
      written in Visual Basic.

PMID- 9767469
TI  - Granulocyte-macrophage colony-stimulating factor induces the differentiation of
      murine erythroleukaemia cells into dendritic cells.
AB  - Dendritic cells (DC) are professional antigen-presenting cells (APC) within the
      immune system and antigen-pulsed DC can be used as an effective vaccine for
      active immunotherapy of cancer. Granulocyte-macrophage colony-stimulating factor
      (GM-CSF) plays an important role in the generation of DC. We previously showed
      that GM-CSF can induce murine erythroleukaemia cells (FBL-3) to differentiate
      into monocyte-like cells. To develop a new vaccinating method to stimulate the
      host immune response to leukaemia, we further investigate whether FBL-3 cells
      induced by GM-CSF can differentiate into DC in the present study. After being
      treated with GM-CSF, FBL-3 cells expressed high levels of 33D1 and NLDC-145,
      which are the specific markers of DC. The expression of MHC-II, B7-1, B7-2 and
      vascular cell adhesion molecule-1 (VCAM-1) was up-regulated markedly; the typical
      morphology of DC were also observed by electron microscopy. Functionally, the GM
      CSF-induced FBL-3 cells could apparently stimulate the proliferation of naive
      allogeneic and autologous T lymphocytes and induce the generation of specific CTL
      more efficiently than the wild-type FBL-3 cells. Mice immunized with GM-CSF
      induced FBL-3 cells could resist the subsequent challenge with the wild-type FBL
      3 cells. Collectively, these data indicate that GM-CSF differentiates murine
      erythroleukaemia cells into DC phenotypically, morphologically and functionally.
      FBL-3-derived DC can be used as a new type of vaccine. Our results may have
      important implications for the immunotherapy of leukaemia.

PMID- 9767473
TI  - Real-time three-dimensional imaging of macroscopic structures.
AB  - We describe an extremely simple method of obtaining optically sectioned images
      with conventional low-power imaging systems in real time. A single spatial
      frequency grid pattern is projected onto an object. Images taken at three spatial
      positions of the grid projection are processed to provide 3D images of
      macroscopic structures.

PMID- 9767474
TI  - Simultaneous confocal lifetime imaging of multiple fluorophores using the
      intensity-modulated multiple-wavelength scanning (IMS) technique.
AB  - We demonstrate the simultaneous recording of confocal lifetime images of multiple
      fluorophores. The confocal microscope used in the study combines intensity
      modulated laser illumination, lock-in detection and spectral separation of the
      fluorescent light. A theoretical investigation is presented that describes how
      the signal-to-noise ratio (SNR) depends on various factors such as modulation
      frequency, degree of modulation and number of detected photons. Theory predicts
      that, compared with ordinary intensity images, lifetime images will have a SNR
      that is, at best, approximately four times lower. Experimental results are
      presented that confirm this prediction.

PMID- 9767471
TI  - Rapid recruitment of macrophages in interleukin-12-mediated tumour regression.
AB  - In order to study the mechanism of interleukin-12 (IL-12) antitumour activity,
      RH7777 rat hepatoma cells were engineered to express mouse IL-12 (mIL-12)
      (RH7777/mIL-12) under the tight control of doxycycline (dox). The production of
      the mIL-12 protein was regulated by the concentration of dox that was present in
      the culture medium. RH7777/mIL-12 cells appeared to have the same tumorigenic
      activity as did parental RH7777 cells, when subcutaneously injected into
      syngeneic rat (BUF/N) in the absence of dox. However, the tumorigenicity of
      RH7777/mIL-12, but not RH7777, cells were significantly decreased when dox was
      administrated to the animals. In addition, established tumours of RH7777/mIL-12
      cells gradually disappeared upon the induction of mIL-12 by dox. To elucidate the
      kinetic profile of immune cells involved in the mIL-12-induced tumour regression,
      both histological and immunohistochemical analyses were performed 1, 3 and 14
      days after the dox treatment on rats bearing tumours that were approximately 0. 5
      cm in diameter. Tumour-infiltrating macrophages began to appear at the tumour
      site one day after dox treatment. As time elapsed, the number of tumour
      infiltrates including CD4+, CD8+, natural killer (NK) cells and macrophages
      gradually increased. In particular, CD8+ and NK cells constituted the major
      population of the tumour-infiltrated cells. Furthermore, it was found that
      resting peritoneal macrophages (PM) from rats were chemoattracted in response to
      mIL-12. The effects of mIL-12 on PM chemotaxis were reproducibly observed in
      concentrations as low as 0.1 ng/ml. These findings suggest that IL-12 can
      directly recruit macrophages into tumour sites which, in turn, leads to a broad
      and intense immunological response against tumour.

PMID- 9767475
TI  - Evaluating the performance of fluorescence microscopes.
AB  - A simple means of evaluating the performance of fluorescence microscopes is
      described. The proposed test gives an overall figure of merit that takes into
      account all of the important instrumental parameters that determine image
      quality. The essence of the test is to use a specimen whose photobleaching rate
      is a measure of the illumination time-intensity integral. When this time
      intensity integral is controlled, the signal-to-noise ratio in the image of small
      subresolution objects becomes a system-independent measure of light throughput,
      resolution and intrinsic noise.

PMID- 9767476
TI  - Ultrathin fluorescent layers for monitoring the axial resolution in confocal and
      two-photon fluorescence microscopy.
AB  - Monomolecular films of polymerized dimethyl-bis[pentacosadiinoic-oxyethyl]
      ammonium bromide (EDIPAB) provide one- and two-photon excited fluorescence that
      is sufficiently high to quantify the axial resolution of 3-D fluorescence
      microscopes. When scanned along the optical axis, the fluorescence of these
      layers is bright enough to allow online observation of the axial response of
      these microscopes, thus facilitating alignment and fluorescence throughput
      control. The layers can be used for directly measuring and monitoring the axial
      response of 4Pi-confocal microscopes, as well as for their initial alignment and
      phase adjustment. The proposed technique has the potential to supersede the
      conventional technique of calculating the derivative of the axial edges of a
      thick fluorescent layer. Coverslips with EDIPAB-layers can be used as substrates
      for the cultivation of cells.

PMID- 9767477
TI  - Dispersion pre-compensation of 15 femtosecond optical pulses for high-numerical
      aperture objectives.
AB  - The excitation efficiency in two-photon absorption (TPA) microscopy depends
      strongly - owing to the square dependence of the TPA fluorescence on the
      excitation intensity - on the temporal width of the excitation pulse. Because of
      their inherently large frequency bandwidth, ultrashort optical pulses tend to
      broaden substantially because of dispersion from propagation through the
      dispersive elements in the microscope. In this paper, the dispersion
      characteristics of a wide range of microscope objectives are investigated. It is
      shown that the induced dispersion can be pre-compensated in all cases for pulses
      as short as 15 fs. Because of the excellent agreement between the results from
      theoretical modelling and the experimental data, predictions of the possibility
      of dispersion control for microscope objectives in general, as well as for even
      shorter pulses, can be inferred. Since for TPA imaging the background due to
      single photon absorption processes and scattering is independent of the pulse
      width, proper dispersion pre-compensation - which minimizes the pulse duration at
      the focal point and hence maximizes the excitation efficiency - provides optimal
      image contrast in TPA microscopy.

PMID- 9767478
TI  - Desktop X-ray microscopy and microtomography.
AB  - Recent developments in X-ray microtomography have made it possible to miniaturize
      a CT scanner into a versatile and cost-effective desktop system that fits into
      any laboratory environment. The possibilities of the technique are demonstrated
      for a range of applications. It is also shown how an existing scanning electron
      microscope with an X-ray detector can, with a specially developed attachment, be
      transformed into an X-ray microscope and microtomograph.

PMID- 9767479
TI  - A numerical study of resolution and contrast in soft X-ray contact microscopy.
AB  - We consider the case of soft X-ray contact microscopy using a laser-produced
      plasma. We model the effects of sample and resist absorption and diffraction as
      well as the process of isotropic development of the photoresist. Our results
      indicate that the micrograph resolution depends heavily on the exposure and the
      sample-to-resist distance. In addition, the contrast of small features depends
      crucially on the development procedure to the point where information on such
      features may be destroyed by excessive development. These issues must be kept in
      mind when interpreting contact microradiographs of high resolution, low contrast
      objects such as biological structures.

PMID- 9767480
TI  - Measurement-based evaluation of optical pathlength distributions reconstructed
      from simulated differential interference contrast images.
AB  - Recently a method was presented for reconstructing optical pathlength
      distributions (OPDs) from images of weak phase objects obtained by a conventional
      differential interference contrast (DIC) microscope. A potential application of
      this technique is the determination of the mass of biological objects: by
      integrating the optical pathlength over the projected surface of the image of an
      object, a measure of the dry mass, i.e. the total mass of all solid constituents
      present in the object, is obtained. To assess the possibilities of DIC microscopy
      for this application, simulations were performed on computer-generated DIC images
      of objects of various sizes, shapes and orientation angles. After reconstructing
      the OPDs from these images, the integrated optical pathlength of each of the test
      objects was determined, and compared with the expected results. The parameter
      settings used in the reconstruction algorithm were found to be very important in
      obtaining a reliable measurement. Using optimal parameter settings, errors in the
      integrated OPD could be limited to a few per cent for circular objects within the
      investigated size range. For non-circular objects, however, the orientation angle
      of the object relative to the lateral shift was found to influence the measured
      values. Ellipses with their long axes perpendicular to the shift direction had a
      significantly higher integrated OPD than ellipses orientated parallel to the
      shift. By adjusting the reconstruction parameters the effect could be limited,
      but complete elimination of the artefact was not possible within the parameter
      range investigated.

PMID- 9767481
TI  - Energy-filtered cryotransmission electron microscopy of liposomes prepared from
      human stratum corneum lipids.
AB  - We used cryo-TEM to examine the morphology of vesicles formed from lipids of the
      human stratum corneum (hSC). Human stratum corneum lipid liposomes (hSCLLs) were
      prepared in buffer at various pH values, using different preparation methods
      (film method, extrusion, ultrasonication, detergent dialysis). The morphology of
      hSCLLs at pH 7.4 differed markedly from that of liposomes formed by
      phospholipids, showing folds, stacks and membrane thickening. At pH 5.0,
      corresponding to natural conditions at the skin surface, membrane structures are
      essentially the same as those prepared at pH 7.4. Sharp edges in hSCLLs,
      branching membranes and stable membrane stacks were explained by the presence of
      ceramides, the major components and structural elements of human stratum corneum
      lipids (hSCLs). Thickened areas in the membranes may be caused by the local
      accumulation of triacylglycerols and cholesterol esters in the hydrophobic
      interior of the bilayer.

PMID- 9767482
TI  - Physical and chemical changes in polystyrene during electron irradiation using
      EELS in the TEM: contribution of the dielectric function.
AB  - We have performed electron energy-loss spectroscopy analysis of polystyrene in
      the analytical transmission electron microscope in order to evaluate the
      possibility of obtaining both chemical and dielectric information on the polymer
      at the submicrometre scale. Irradiation has also been studied, particularly the
      influence of the specimen temperature on the kinetics of degradation. The main
      results show that polystyrene is resistant to electron beam with a critical dose
      of about 104 C m-2 at 127 K. Spectra could be acquired with doses less than this
      critical dose. We were thus able to propose an identification of the different
      chemical bonds of carbon (including the C-H bond), in agreement with previous X
      ray absorption near-edge structure experiments. The chemical changes in
      polystyrene due to severe irradiation damage are also visible in the carbon K
      edge near-edge structure. At the same time, we calculated the dielectric function
      from the low-loss part of the spectra. Interestingly, this part of the spectrum
      is the most sensitive to irradiation, since great changes can be seen during
      exposure. Lastly, we propose a degradation process, in agreement with all these
      results.

PMID- 9767483
TI  - Estimation of average particle size from vertical projections.
AB  - A new stereological relationship is derived for the estimation of average size
      (average width) of a collection of convex particles in a 3D microstructure. The
      average size is estimated from measurements performed on projected images of the
      microstructure generated by total vertical projections. The stereological
      relationship is as follows: D = IC/(2N0beta). D is the average width, ;IC is the
      average absolute number of intersections between the specifically oriented and
      regularly spaced cycloid shape test lines and particle boundaries observed in the
      total vertical projections, N0 is the total number of particles observed in the
      total vertical projection and the parameter beta is a characteristic of the
      measurement grid; it has units of reciprocal of length. The result is applicable
      to any arbitrary collection of convex particles; the particle orientations need
      not be isotropic. Only 'intersection counts' are required; it is not necessary to
      measure sizes of the particles in the projected images.

PMID- 9767484
TI  - Estimating surface area by the isotropic fakir method from thick slices cut in an
      arbitrary direction.
AB  - The proposed fakir method for estimating surface area is based on counting the
      intersections between the surface lying within a thick slice, and an isotropic
      spatial grid consisting of a combination of linear probes called fakir probes. An
      unbiased procedure using a directly randomized spatial grid rather than sections
      with randomized directions is presented. The method is applicable if perfectly
      registered serial sections of the surface are available in a thick slice while
      the direction of the slice can be arbitrary. The efficiency of the fakir method
      using different arrangements of orthogonal triplets of fakir probes is evaluated
      and it is shown that mutually shifted probes are superior to non-shifted ones.
      The application software for interactive counting of intersections between
      computer-generated fakir probes and the surface within the stack of digitized
      images is described and demonstrated by two examples: estimation of the surface
      area of individual tobacco cell chains using a confocal microscope, and
      estimation of the total area of exposed surface of mesophyll cells in a barley
      leaf using a wide-field transmission microscope.

PMID- 9767485
TI  - Characterization of nanophase Al-oxide/Al powders by electron energy-loss
      spectroscopy.
AB  - Al nanoparticles were prepared by the inert gas condensation method. After
      passivation with oxygen and air exposure we obtained a powdered sample of an Al
      oxide/Al nanocomposite material. In the present paper we describe the use of the
      electron energy-loss spectroscopy (EELS) technique in a transmission electron
      microscope to characterize such nanostructured powders compared with a
      microcrystalline commercial aluminium foil. Energy-filtered images showed the
      presence of an alumina overlayer of approximately 4 nm covering the aluminium
      nanoparticles (23 nm in diameter). EELS analysis enabled us to determine the
      total amount of Al2O3 and metallic Al and the structure of the alumina
      passivation overlayer in the sample. In particular, the extended energy-loss fine
      structure analysis of the data showed a major presence of Al tetrahedrally
      coordinated with oxygen in the alumina passivation layer of Al nanoparticles
      instead of the octahedral coordination found for a conventional Al foil. This
      surprising effect has been attributed to the nanoscopic character of the grains.
      The analysis of the electron-loss near-edge structure also determines the
      presence of a certain degree of aggregation in this kind of powdered sample as
      result of the coalescence of the nanocrystalline grains. The procedure presented
      here may have the potential to solve other problems during characterization of
      nanostructured materials.

PMID- 9767486
TI  - A quantitative method for analysing AFM images of the outer surfaces of human
      hair.
AB  - Cuticle step height is an important parameter for the quantitative assessment of
      human hair. This paper describes a novel, computational method for the rapid
      calculation of step heights from atomic force microscope images obtained from
      large numbers of specimens. Such an approach is necessary to allow a statistical
      analysis of the inherently wide distribution of cuticle step heights
      characteristic of a single hair sample. The method described will be of use to
      cosmetic formulation chemists and forensic scientists and also to dermatologists
      in the field of disease diagnosis.

PMID- 9767487
TI  - Neurofilament-L homopolymers are less mechanically stable than native
      neurofilaments.
AB  - Neurofilaments are cytoskeletal components of neurones that are thought to play
      an important structural role in the axon. Specific functions of neurofilaments
      are not yet well defined; however, other intermediate filaments are known to have
      structural and mechanical functions in different cell types. The atomic force
      microscope (AFM) can be used to visualize and manipulate biological structures
      through direct physical contact. This allows the AFM to be used to probe the
      mechanical properties of these structures. In this paper we present AFM images of
      native neurofilaments isolated from bovine spinal cord, composed of NF-L, NF-M
      and NF-H, and filaments polymerized in vitro from purified NF-L. Morphologically
      these structures, in solution and under ambient conditions, are in agreement with
      previous data from electron microscopy. However, repeated scanning of NF-L
      homopolymers (in solution) produced significant disruptions of segments of
      filaments, both within and at the ends of the filaments. This disruption resulted
      in complete loss of portions of the filaments and in breaks in the continuity of
      the filaments. Repeated scanning of isolated native neurofilaments under similar
      conditions produced no detectable structural changes. Under extremely high
      applied forces the native neurofilaments were bent and distorted by the action of
      the AFM tip, but were never broken. These data suggest that purified NF-L is not
      sufficient to confer complete mechanical stability to neurofilaments.

PMID- 9767488
TI  - Global spatial sampling with isotropic virtual planes: estimators of length
      density and total length in thick, arbitrarily orientated sections.
AB  - Existing design-based direct length estimators require random rotation around at
      least one axis of the tissue specimen prior to sectioning to ensure isotropy of
      test probes. In some tissue it is, however, difficult or even impossible to
      define the region of interest, unless the tissue is sectioned in a specific,
      nonrandom orientation. Spatial uniform sampling with isotropic virtual planes
      circumvents the use of physically isotropic or vertical sections. The structure
      that is contained in a thick physical section is investigated with software
      randomized isotropic virtual planes in volume probes in systematically sampled
      microscope fields using computer-assisted stereological analysis. A fixed volume
      of 3D space in each uniformly sampled field is probed with systematic random,
      isotropic virtual planes by a line that moves across the computer screen showing
      live video images of the microscope field when the test volume is scanned with a
      focal plane. The intersections between the linear structure and the virtual
      probes are counted with columns of two dimensional disectors. Global spatial
      sampling with sets of isotropic uniform random virtual planes provides a basis
      for length density estimates from a set of parallel physical sections of any
      orientation preferred by the investigator, i.e. the simplest sampling scheme in
      stereology. Additional virtues include optimal conditions for reducing the
      estimator variance, the possibility to estimate total length directly using a
      fractionator design and the potential to estimate efficiently the distribution of
      directions from a set of parallel physical sections with arbitrary orientation.
      Other implementations of the basic idea, systematic uniform sampling using probes
      that have total 3D x 4pi freedom inside the section, and therefore independent of
      the position and the orientation of the physical section, are briefly discussed.

PMID- 9767489
TI  - Star length distribution: a volume-based concept for the characterization of
      structural anisotropy.
AB  - Determination and quantification of anisotropy is of great interest in research
      fields dealing with physical structures or surface textures. In this paper, a
      volume-based method is presented, which essentially determines the mean object
      length in a certain direction for a typical point within a structure or texture.
      The mean object lengths for all orientations together form the so-called star
      length distribution (SLD). The validity and the accuracy of the SLD method are
      investigated, and illustrated by applying it to trabecular bone. By using a line
      sampling algorithm, the relation with other anisotropy measures could be studied
      analytically. Preliminary tests suggest that with SLD a more exact description of
      the mechanical properties of porous structures may be obtained than with other
      anisotropy measures. However, due to possible secondary orientations that become
      apparent with SLD, a fabric tensor must be of rank higher than two in order to
      properly describe an orthogonal structure mathematically.

PMID- 9767490
TI  - Assessment of fibre orientation in reinforced concrete using Fourier image
      transform.
AB  - In this study, ribbon-shaped amorphous cast-iron fibres were used to reinforce a
      concrete matrix. X-ray photographs have been taken to detect fibres in situ.
      Their orientation has been investigated by automatic image analysis methods.
      However, this measurement should not be influenced by the digitization on the
      square frame of the analyser. For that purpose, the Fourier transform was used
      rather than the rose of direction method. This analysis revealed the transverse
      isotropic nature of the spatial arrangement of these fibres, whose axis of
      revolution corresponds to the concrete casting axis. Such a morphological
      characterization of the fibre-reinforced concrete reveals its mechanical
      behaviour.

PMID- 9767491
TI  - 3D microscopy of transparent objects using third-harmonic generation.
AB  - It is demonstrated that third-harmonic generation (THG) near interfaces in the
      refractive index or the third-order nonlinear susceptibility (chi(3)) permits
      three-dimensional imaging of transparent objects. The nonlinear dependence of THG
      on the excitation power provides inherent optical sectioning. At the same time,
      the nonresonant nature of THG, in combination with the near-IR excitation
      wavelengths used (1-2 um), render this technique potentially (biologically)
      nondamaging and nonbleaching. A specific property of THG imaging is its
      sensitivity to - and potential use for imaging of - the relative orientation of
      interfaces with respect to the axis of propagation of the excitation radiation.

PMID- 9767492
TI  - HREM and STEM of intergranular films at zinc oxide varistor grain boundaries.
AB  - Grain boundaries in model ZnO-Bi2O3 and ZnO-Bi2O3-CoO varistors and a commercial
      multicomponent varistor have been characterized by high-resolution electron
      microscopy (HREM) and scanning transmission electron microscopy (STEM), in order
      to determine the relationship between Bi grain boundary segregation and formation
      of thin intergranular films. By controlling Bi2O3 content, applied pressure and
      temperature, the grain boundary Bi excess has been systematically varied from
      nearly zero to GammaBi = 1 x 1015 cm-2 ( approximately 1 monolayer), as measured
      by HB 603 STEM using an area-scan method. HREM shows that intergranular amorphous
      films are clearly distinguishable in samples with GammaBi > 8 x 1014 cm-2. These
      films range in thickness, depending on the Bi excess, from 0.6 to 1.5 nm. Similar
      films of approximately 1 nm thickness are widely observed in the commercial
      varistor. The composition of the films is a ZnO-Bi2O3 solid solution, which is in
      all cases more enriched in ZnO than the bulk eutectic liquid. The Bi-doped grain
      boundaries in ZnO varistors therefore contain an intergranular amorphous film
      which has not only an equilibrium thickness, but also a distinct equilibrium
      composition.

PMID- 9767493
TI  - Quantitative analysis of valence electron energy-loss spectra of aluminium
      nitride.
AB  - The optical properties and electronic structure of aluminium nitride are
      determined using valence electron energy-loss spectroscopy in a dedicated
      scanning transmission electron microscope. Quantitative analysis of the
      experimental valence electron energy-loss spectra to determine the electronic
      structure encompasses single scattering deconvolution of the valence electron
      energy-loss spectra to calculate the energy-loss function, Kramers-Kronig
      analysis of the energy-loss function to reveal the complex dielectric function,
      transformation of the dielectric function into the optical interband transition
      strength via optical property relations and finally critical-point analysis of
      the interband transition strength. The influence of both experimental and
      analytical parameters on the final result was studied systematically to define
      and improve the understanding of the methods. To check the reliability of this
      technique the interband transition strength determined was compared with results
      of vacuum ultraviolet spectroscopy. Good agreement was found if sample
      preparation was taken into account. The preparation of the specimen for the
      transmission electron microscopy has an effect on the electronic structure.
      Quantitative analysis of valence electron energy-loss spectroscopy, using the
      methods presented, is an important and capable method to determine the electronic
      structure of materials and it has the benefit of high spatial resolution.

PMID- 9767494
TI  - A simple method for the acquisition of high-quality digital images from analog
      scanning electron microscopes.
AB  - A method is described for converting video signals of analog scanning electron
      microscopes (SEMs) into digital images of high quality. A plug-in card
      commercially available for personal computers is used for the on-line
      analog/digital conversion. A Windows application program written by the authors,
      together with low-level software drivers supplied with the plug-in card, allow
      digital images to be recorded, to be displayed simultaneously on the computer
      monitor and to be saved as a file in a standardized format. Compared to
      conventional photographic images obtained from the SEM camera system, the digital
      images possess superior sharpness of outline, excellent image definition,
      diminished noise and well-defined grey-scale tones. This method provides SEM
      images of high quality for less than $1000 from most older analog SEMs. In
      addition, the advantages of digital image processing can be applied to analog
      SEMs, including contrast enhancement, digital filtering and multichannel
      recording.

PMID- 9767495
TI  - Quantitative X-ray microanalysis of solutes in individual plant cells: a
      comparison of microdroplet and in situ frozen-hydrated data.
AB  - Two different approaches to X-ray microanalysis were tested and compared. These
      were the analysis of sap droplets extracted from individual cells (plants grown
      and analysed in Bangor, U.K.), and the analysis of cells in situ in frozen tissue
      (plants grown and analysed in Hannover, Germany). The data suggest that both
      these methods can produce quantitative data accurately reflecting in vivo
      concentrations in cereal leaf epidermal cells. The relative merits of the two
      procedures are discussed with reference to possible sources of error and their
      application to other cell types. Bulk wheat leaf tissue concentrations of K and
      Cl did not differ significantly between the two locations, but Ca concentration
      was significantly higher in the plants grown in Hannover. Microdroplet analysis
      invariably yielded linear responses in the range of concentrations found in plant
      tissue (r2 for Ca > 0.97, r2 for K, Cl > 0.99), and interference of other
      components of the sap was minimal. The calibration curves for the frozen-hydrated
      material were typically linear in the same range of concentrations (r2 for K, Ca,
      Cl > 0.95), and the results for K and Cl concentration in these samples were
      highly consistent with those measured in the microdroplet experiments. In wheat,
      for example, the cellular Cl concentration varied between 12 mM and 119 mM, but
      no significant differences were found between the two techniques of measurement.
      The results for cellular Ca differed in a manner which might be predicted from
      the results of the bulk tissue analyses.

PMID- 9767496
TI  - X-ray microanalysis of native airway surface liquid collected by cryotechnique.
AB  - The airway surface liquid (ASL) that lines the surface epithelium of the
      tracheobronchial tree is of vital importance to the airway defence against
      microbial invasion and damage due to environmental factors. Little is known about
      the ASL collected in situ in native conditions, owing to difficulties in
      collecting ASL without causing damage to the airway mucosa. We have developed a
      method to collect and analyse the elemental composition of tracheal ASL in
      pathogen-free mice. A specially designed cryoprobe, adapted to the internal
      curvature of the mouse trachea, was used to collect the native ASL from the
      tracheal surface. The complete ASL elemental composition including [Na] = 5.5 +/-
      0.3, [Cl] = 1.3 +/- 0.3, [K] = 1.1 +/- 0.2, [Ca] = 1.2 +/- 0.3, [P] = 1.5 +/-
      0.8, [S] = 1.7 +/- 0.4 and [Mg] = 1.3 +/- 0.4 mmol L-1 was determined by X-ray
      micro analysis. We demonstrate here that the technique that we used for ASL
      collection maintained perfectly the airway epithelial integrity and
      functionality.

PMID- 9767497
TI  - Cryo-TEM liquid nitrogen splash guard.
AB  - A simple aluminium splash guard provides protection for both microscopes and
      operators during cryo-transfer procedures.

PMID- 9767498
TI  - Intra-abdominal manifestations of Henoch-Schonlein purpura.
AB  - Gastrointestinal involvement occurs in approximately two thirds of children with
      Henoch-Schonlein Purpura (HSP) and usually is manifested by abdominal pain.
      Abdominal symptoms precede the typical purpuric rash of HSP in 14-36%; the
      symptoms may mimic an acute surgical abdomen and result in unnecessary
      laparotomy. Major complications of abdominal involvement develop in 4.6% (range
      1.3-13.6%), of which intussusception is by far the most common. The
      intussusceptum is confined to the small bowel in 58%; its frequent
      inaccessibility to demonstration by contrast enema means that ultrasonography is
      the investigation of choice. Ultrasonography complements serial clinical
      assessment, clarifies the nature of the gastrointestinal involvement and reduces
      the likelihood of unnecessary surgery. Bowel ischaemia and infarction, intestinal
      perforation, fistula formation, late ileal stricture, acute appendicitis, massive
      upper gastrointestinal haemorrhage, pancreatitis, hydrops of the gallbladder and
      pseudomembranous colitis are seen infrequently. Earlier diagnosis and prompt
      treatment of intra-abdominal complications has reduced the mortality from 40% to
      almost zero.

PMID- 9767499
TI  - The long QT syndrome and seizures in childhood.
AB  - Children with the long QT syndrome (LQTS) are prone to life threatening
      ventricular arrhythmias. These arrhythmias may result in syncope and seizures
      that are often attributed incorrectly to a seizure disorder or to common
      fainting. The untreated mortality for symptomatic children with the LQTS is high
      but is improved significantly with therapy. Paediatricians should be aware of the
      presentations of the syndrome. Recommendations for screening for the syndrome are
      given.

PMID- 9767500
TI  - Policy statement on breastfeeding. The Australian College of Paediatrics.

PMID- 9767502
TI  - Is breast feeding in bed always a safe practice?
AB  - OBJECTIVES: To examine whether infants who are being breast fed in their mother's
      bed are at increased risk of accidental suffocation. MATERIALS AND METHODS:
      Review of all cases of unexpected infant death occurring in South Australia,
      Australia during 1996 was undertaken to ascertain whether any cases of sudden
      infant death had occurred in association with breast feeding in the parental bed.
      All infants had death scene examinations, history reviews and full autopsies
      performed. RESULTS: Three of a total of 28 cases of unexpected infant death were
      identified where accidental asphyxia associated with breast feeding-related
      cosleeping was considered a likely cause of death. Maternal fatigue was a factor
      in each of the three cases. There were nine SIDS cases and 16 other cases which
      included non-accidental injury, accidental asphyxia, congenital cardiovascular
      disease and sepsis. CONCLUSIONS: Accidental asphyxia is a rare but possible
      outcome if mothers fall asleep in bed with their infants while breast feeding.
      Nursing mothers should be made aware of the potential dangers of fatigue and
      sedation in such circumstances. Breast feeding out of bed, or in the company of a
      second person who can ensure the safety of the infant if breast feeding is
      occurring in bed may prevent these unfortunate fatalities.

PMID- 9767501
TI  - Young people with spina bifida: transfer from paediatric to adult health care.
AB  - An expectation of health care for young people with disability is that quality
      coordinated care continues to be available as they pass from the paediatric to
      the adult health care system. While individual clinicians provide this service
      well, the widespread absence of coordinated multidisciplinary care for young
      people with spina bifida in the adult health care system is a major deficiency.
      This paper describes the planning and implementation that underpinned the
      transfer of 10 young people with spina bifida from a paediatric to an adult
      service. The range of structural, financial and 'cultural' barriers that need to
      be overcome before patients can be successfully transferred is highlighted;
      lessons learned from this model may serve to facilitate the development of other
      transfer services.

PMID- 9767503
TI  - Renal tract abnormalities detected in Australian preschool children.
AB  - OBJECTIVE: To quantify the incidence of abnormalities in urinalysis and blood
      pressure from preschool children and their predictive value in detecting renal
      disease within an Australian community. METHODOLOGY: Urine samples, blood
      pressure and height measurements and parental reports of significant medical
      problems were collected from a total of 9355 South Australian preschool children.
      Seven hundred and forty-three children with abnormal results were investigated in
      a nephrology outpatient clinic. A control group of 357 children with no
      detectable abnormality were also recalled, examined and, where appropriate,
      investigated. RESULTS: Nine thousand, three hundred and fifty-five children were
      tested. Of these, 0.81% were shown to have a clinically significant renal tract
      abnormality. The findings included children with urinary tract infections, vesico
      ureteric reflux, glomerular disease, renal calculi, essential hypertension and a
      renal neoplasm. While dipstick-based methods were the most specific indicators of
      renal tract abnormalities, measurement of blood pressure and urinary beta2
      microglobulin were also important in detecting abnormalities. Screening for
      glycosuria did not result in the detection of significant undiagnosed
      abnormalities. In the control group with no abnormality detected at testing,
      there was one case each of aortic coarctation, polycystic kidney disease and
      vesico-ureteric reflux diagnosed. CONCLUSION: Undiagnosed renal tract
      abnormalities are present in many Australian preschool children. Most are
      detectable by a thorough history, examination and urinalysis.

PMID- 9767504
TI  - Relative bioavailability and plasma paracetamol profiles of Panadol suppositories
      in children.
AB  - OBJECTIVE: To determine the relative bioavailability and plasma paracetamol
      concentration profiles following administration of a proprietary formulation of
      paracetamol suppositories to postoperative children. METHODOLOGY AND RESULTS:
      Study A-eight children undergoing minor surgery had blood samples collected
      following the rectal administration of either a 250 mg or 500 mg paracetamol
      suppository on one day and an equivalent oral dose on the following day. A mean
      dose of 13 mg/kg gave a mean Cmax (Tmax) of 7.7 mg/L (1.6 h) and 4.9 mg/L (2.0 h)
      following oral and rectal administration, respectively. The mean relative rectal
      bioavailability was 78% (95% confidence interval of 55-101%). Study B-20 children
      undergoing tonsillectomy and/or adenoidectomy were randomly assigned to receive a
      postoperative dose of 500 mg of paracetamol either as 2 x 250 mg liquid filled or
      1 x 500 mg hard wax Panadol suppository. A mean dose of 25 mg/kg produced mean
      maximum plasma paracetamol concentrations of 13.2 mg/L and 14.5 mg/L at 2.1 and
      1.9 h for the hard and liquid filled suppository, respectively. The absorption
      rate constants and areas under the curves suggested no difference in the rate or
      extent of absorption between the two formulations. CONCLUSION: Absorption of
      paracetamol following rectal administration of Panadol suppositories to
      postoperative children is slower and reduced as compared to oral therapy. The
      hard wax and liquid filled products have similar absorption characteristics. The
      usually quoted antipyretic therapeutic range for paracetamol is 10-20 mg/L,
      although 5 mg/L may be effective. A single rectal dose of 25 mg/kg will obtain
      this lower concentration within 1 h of administration and maintain it for up to 6
      h. When given in an appropriate dose for analgesia, maximum plasma paracetamol
      concentrations would be available in the immediate postoperative period if the
      rectal dose was given 2 h before the planned end of the procedure.

PMID- 9767505
TI  - Residential mobility and sudden infant death syndrome.
AB  - OBJECTIVE: To examine whether permanent domicile change of the mother, thence the
      infant, or temporary relocation of the infant away from his or her usual place of
      residence affects the risk of sudden infant death syndrome (SIDS). DESIGN: A case
      control nation-wide epidemiological study. SETTING: New Zealand between the years
      1987-90. PARTICIPANTS: From the 485 SIDS diagnoses over this time, parents of 393
      (81%) SIDS infants consented to participate and these comprise the cases.
      Controls were selected by randomly sampling 1800 infants from all babies born
      over 78% of the country. Parents of 1592 (88%) control infants participated.
      RESULTS: Infants away from their usual address were 1.70 (95% CI: 1.09, 2.66)
      times more likely to die from SIDS than infants sleeping at home, after
      controlling for likely confounding factors. A partial explanation for this
      finding was that SIDS infants were less likely to have been mainly breast fed in
      the last two days and were less likely to have shared a room with at least one
      adult at the nominated sleep/death. Infants of mothers who shifted house after
      their birth, infants having mothers who shifted house within a year prior to the
      study interview date, and infants who slept at numerous different houses were
      associated with an increased relative risk for SIDS at the univariate level, but
      not after adjustment. CONCLUSIONS: Infants are less likely to die in their
      accustomed residential environment. This finding needs confirmation by other
      studies.

PMID- 9767506
TI  - 22q11 deletions in patients with conotruncal heart defects.
AB  - OBJECTIVE: To ascertain the frequency of 22q11 deletions in a representative
      population of conotruncal heart defects (CTD) and determine which children are at
      risk of having a deletion. METHODOLOGY: A clinical and laboratory evaluation of
      90 children with CTD, including isolated and syndromic cases. RESULTS: Fifteen
      children (17%) were shown to have 22q11 deletions by fluorescence in situ
      hybridization (FISH) studies with the Oncor probe N25. Varying degrees of
      developmental delay/learning disabilities and facial dysmorphism were common in
      these children. None of the isolated cases without dysmorphism had a deletion.
      CONCLUSION: 22q11 deletions are a significant cause of a specific form of
      congenital heart disease, CTD. It is important to have a high index of suspicion
      of the 22q11 deletion disorders in children with CTD and other extracardiac
      manifestations so that the diagnosis can be made early and appropriate
      interventions implemented.

PMID- 9767507
TI  - Effects of blood transfusion on left ventricular output in premature babies.
AB  - OBJECTIVE: To investigate the acute effects of red blood cell transfusion on
      haemodynamics in preterm babies. SETTING: A neonatal unit in a University
      Hospital. PATIENTS: Preterm babies whose postnatal age was less than four weeks
      and who required red blood cell transfusion. MEASUREMENT: Cardiac output and left
      ventricular systolic function was determined using Doppler echocardiography
      before, one hour and 24 h after red blood cell transfusion. Blood pressure and
      haematocrit were also recorded at the same time. Mixed-effects regression model
      was used to analyse the effect of blood transfusion on left ventricular function
      and cardiac output. RESULTS: 57 preterm babies were recruited. Univariate
      analysis showed that cardiac index decreased significantly 24 h after transfusion
      (P<0.05). Systemic red cell transport increased by an average of 11.1% 24 h after
      transfusion (P<0.05). Multivariate analysis showed that the cardiac index was
      negatively associated with haematocrit and the index was higher in male babies.
      CONCLUSION: There was a significant drop in cardiac index and an increase in
      systemic red cell transport 24 h after transfusion in premature babies.

PMID- 9767508
TI  - End tidal carbon monoxide concentration in childhood haemolytic disorders.
AB  - OBJECTIVES: Endogenous carbon monoxide (CO) is produced mainly by heme
      catabolism. As CO is excreted solely by the lung, a simple technique for
      measuring the end tidal carbon monoxide (ETCO) level was assessed as a method for
      screening for haemolytic disease in children. METHODS: Two end expiratory breath
      samples were collected from normal children and from children with haemolytic
      disease using a one way valve connector between a mouth piece and an anaesthetic
      bag. The samples were analysed by gas chromatography for CO and carbon for
      dioxide (CO2). The CO2 value was used to normalise the CO value to an alveolar
      concentration. Carboxyhaemoglobin (HbCO) also was measured in the patient group
      for correlation analysis with ETCO. RESULTS: A total of 21 children with beta
      thalassaemia major, 15 children with other haemolytic diseases (hereditary
      spherocytosis n=8, haemoglobin H disease n=3 and thalassaemia intermedia n=4) and
      23 normal children were studied. The mean ETCO concentrations in the three groups
      were 3.21 p.p.m., 7.41 p.p.m. and 0.69 p.p.m., respectively, which were
      significantly different from each other (P<0.0001). There was a significant
      correlation between ETCO and HbCO in the patient groups (r=0.85; P<0.0001).
      CONCLUSIONS: The end expiratory breath collection device is a simple and feasible
      sample collection method. The results confirm that ETCO can be used clinically to
      distinguish children with a variety of haemolytic disorders from normal subjects.

PMID- 9767509
TI  - Paediatricians: referral rates and speech pathology waiting lists.
AB  - OBJECTIVE: This study aimed to examine paediatricians' training in and
      understanding of communication development and disabilities and their attitudes
      to speech pathology waiting lists and management practices. The relationship
      between these factors and referral rates was also investigated. METHODOLOGY: A
      total of 229 paediatricians registered with the Australian College of Paediatrics
      participated in the study in November 1996. They answered 15 multiple-choice
      questions designed to collect demographic information and data pertaining to
      their training and understanding of communication development and disabilities.
      The survey also obtained data on referral rates to public and private speech
      pathology services and on paediatricians' perceptions of speech pathology waiting
      lists and possible management strategies. RESULTS: Referral rate to public and
      private speech pathology services was found to be associated with the quality of
      paediatricians' training in and knowledge of communication development and
      disabilities. Paediatricians who had regular contact with speech pathologists
      were also more likely to make more referrals. Waiting lists had a negative
      influence on referral rate. Treatment rather than assessment waiting lists were
      preferred. Paediatricians believed the best solution to speech pathology waiting
      lists was an increase in staffing levels particularly in community health
      centres. Respondents reported that 1-4 months was an acceptable time to wait for
      speech pathology care and indicated the order of importance of factors for
      prioritising children. CONCLUSIONS: The results have important implications for
      developing best practice models for improving referral processes and access to
      speech pathology services for children with communication disabilities.

PMID- 9767510
TI  - Predischarge screening of very low birthweight infants by click evoked
      otoacoustic emissions.
AB  - OBJECTIVE: To evaluate the role of transient evoked otoacoustic emission (TEOAE)
      in screening very low birthweight (VLBW) neonatal intensive care unit (NICU)
      graduates for hearing loss in comparison with visual reinforcement orientation
      audiology (VROA) at 10 months. METHODOLOGY: The study population was all VLBW
      neonatal survivors discharged from a single regional NICU at John Hunter
      Childrens Hospital (JHCH), Newcastle, New South Wales, Australia, between April
      1994 and March 1996. A TEOAE screen was performed prior to discharge and repeated
      if necessary until a pass was obtained in at least one ear. Infants were further
      screened by VROA at their local Australian Hearing Services (AHS) office at 10
      months corrected age. Repeated TEOAE failures were referred directly for an ENT
      opinion. RESULTS: A total of 193 infants were eligible for enrolment during the
      study period. One hundred and forty-four (75%) received TEOAE testing. The median
      age of first screen was 36 weeks gestational age. Ninety-five (66%) of infants
      tested passed on a single screen. Of the remaining 49 infants, 26 passed on
      retesting (overall pass rate 84%). Twenty-three (16%) were deemed to have failed
      the TEOAE screen. Of the 121 infants who passed TEOAE, only 67 (55%) completed
      VROA. Two of these infants have a high frequency sensorineural loss and one of
      them has been aided. In the 23 who failed TEOAE, nine have subsequently had
      normal VROA, another, though not tested is clinically normal. three have hearing
      loss with middle ear disease and eight have confirmed sensorineural deafness, all
      aided. One infant has died and an infant with Down's syndrome has been adopted
      out of the area. It is of interest to note that the eight aided infants are all
      of less than 28 weeks gestation. If we restrict analysis to infants with
      completed VROA testing, the TEOAE has a 97% negative predictive value for
      sensorineural deafness and a 38% positive predictive value. CONCLUSIONS: This
      study has highlighted both the prevalence of hearing impairment in the very
      premature survivors and difficulties in compliance with a VROA based hearing
      screen. We see an advantage in directing resources towards an early screening
      test, such as TEOAE, that can be applied while the target population is still
      captive.

PMID- 9767511
TI  - A randomized controlled trial of two methods for collection of sterile urine in
      neonates.
AB  - OBJECTIVE: To test whether urethral catheterization (UC) is better than
      suprapubic bladder aspiration (SPA) as a method for collection of sterile urine
      in neonates. METHODS: Thirty-three babies, requiring sterile collection of urine,
      were randomly assigned to either urethral catheterization (n=16), median
      gestation 28+/-3.9 weeks, median birth weight 968 g (range 650-4100) or SPA
      (n=17), median gestation 26+/-5.6 weeks, median birth weight 926 g (range 771
      4070). The primary outcome was success in obtaining urine. Secondary outcomes
      were complications and urine culture results. RESULTS: Some urine was obtained in
      11 (64.7%) babies in the SPA group and in 13 (81.2%) babies in the catheter
      group. Sufficient urine for analysis (>0.5 ml) was obtained in 10 (58.8%) in the
      SPA group versus 5 (31.2%) babies in the catheter group. There were more
      contaminated specimens in the catheter group but this was not significant in this
      small study. CONCLUSIONS: In this small randomized controlled trial urethral
      catheterization offered no significant advantage over SPA.

PMID- 9767512
TI  - Magnetic resonance imaging evaluation of the pituitary gland and hypothalamus in
      thalassaemic children with elevated serum ferritin levels.
AB  - OBJECTIVE: Despite modern treatment with hypertransfusion and chelation therapy,
      growth retardation continues to be observed in a significant proportion of
      thalassaemic children. The underlying reason remains unclear, but hypothalamic
      pituitary axis disorder has been implicated. We aimed to assess iron overloading
      in the hypothalamus and pituitary gland in thalassaemic children with elevated
      serum ferritin, with and without growth retardation. METHODOLOGY: Twelve
      thalassaemic children on hypertransfusion and chelation therapy with high serum
      ferritin were investigated with magnetic resonance imaging (MRI). Five children,
      all over 10 years of age, had growth retardation. Gradient recalled echo sequence
      was used to highlight any susceptibility effect that could be due to iron in the
      hypothalamus or pituitary gland. RESULT: There was no evidence of abnormal
      hypointense signal in the hypothalamus or pituitary gland in the patients
      studied, regardless of the presence of growth retardation. CONCLUSION: There was
      no apparent characteristic MRI appearances of iron deposition in the hypothalamus
      or pituitary gland in thalassaemic children with high serum ferritin.

PMID- 9767513
TI  - The musculoskeletal complications of cystic fibrosis.
AB  - OBJECTIVE: To determine the spectrum of musculoskeletal complications of cystic
      fibrosis (CF) in a paediatric population in Australia. METHOD: Clinical
      assessment followed by serology and bone scan on patients attending a specialized
      CF clinic. RESULTS: Of 125 patients studied, 21 had musculoskeletal
      complications, 17 attributable to CF. Eleven had joint involvement (six
      hypertrophic pulmonary osteoarthropathy (HPOA)), one CF arthropathy, two
      ciprofloxacin induced arthralgia, one joint contracture following long-line
      placement, one chest infection associated arthralgia), four kyphosis (two also
      with HPOA) and two thoracic deformity. HPOA was associated with older age, lower
      average pulmonary function and lower average Shwachman score. Three patients with
      HPOA died within 12 months of reporting symptoms. Kyphosis was also associated
      with older age and lower pulmonary function. CONCLUSION: Increasing age with
      deteriorating clinical and pulmonary function were associated with a higher
      incidence of musculoskeletal involvement. The development of symptomatic HPOA is
      a marker of poor prognosis.

PMID- 9767514
TI  - Establishment of a normal range of penile length in preterm infants.
AB  - RATIONALE: Recognition of micropenis is important because it may be the only
      obvious manifestation of pituitary or hypothalamic hormone deficiencies.
      Alternatively it may indicate the presence of dysgenetic testicular tissue with
      malignant potential. Previously published normal ranges for premature males are
      based on small sample sizes, with few infants <30 weeks and none <28 weeks.
      SETTING: Intensive and Special Care Nurseries, Royal Women's Hospital, Melbourne,
      Victoria. SUBJECTS: 188 consecutive male infants, inborn and outborn, with
      gestational age <37 completed weeks were examined in the first week of life. They
      included multiple births (n=51) and small for gestational age infants (n=16).
      Infants with hypospadias (n=3) or an endocrine disorder (n=1) were excluded from
      the study. MANOEUVRE: Stretched penile length was determined by a single examiner
      (RT) using a standardized measure. RESULTS: A mean penile length with associated
      95% confidence intervals is described for infants between 24 and 36 weeks
      inclusive. The relationship between penile length (PL, cm) and gestational age
      (GA, weeks) was: PL=2.27+0.16 GA. CONCLUSION: This study confirms the normal
      range for penile length of premature male infants 30-36 weeks and defines the
      normal range <30 weeks. This should prove useful to paediatricians, paediatric
      surgeons and endocrinologists dealing with the increasing number of surviving
      male infants <30 weeks in whom penile size is questioned.

PMID- 9767515
TI  - Do children need to be monitored after electric shocks?
AB  - OBJECTIVE: To determine whether cardiac monitoring is required in children
      sustaining electric shock at Australian household voltage. METHODOLOGY: Records
      of patients admitted via the Emergency Department of Princess Margaret Hospital
      for Children, Perth, Australia, for the period 1968-96 were retrospectively
      reviewed. The initial ECG findings of patients with an electric shock were
      recorded, and the development of any arrhythmia. RESULTS: Forty-four patients
      were identified, 40 of whom had sustained a household electrical injury. One
      patient had an abnormal ECG on admission, none developed an arrhythmia and all
      survived. CONCLUSIONS: Routine cardiac monitoring is not required after exposure
      to Australian household electricity supply if the child is asymptomatic and has a
      normal ECG on presentation.

PMID- 9767517
TI  - A Chinese girl with Leigh syndrome: effect of botulinum toxin on dystonia.
AB  - Leigh syndrome is a form of neurodegenerative disease which is associated with
      intracranial infarcts. The diagnosis is made by finding hyperlactacidaemia
      together with cerebral infarcts on neuroimaging. We report a 4-year-old Chinese
      girl with Leigh syndrome who had several atypical features. She presented with
      generalized dystonia and developmental regression. In addition, she suffered from
      an unusual feature of bladder dystonia. This patient appeared to be suffering
      from respiratory chain complex I deficiency from studies on cultured skin
      fibroblasts. Assays for respiratory chain enzymes as well as mitochondrial DNA
      point mutations and major deletions in muscle were normal. Dystonia persisted
      despite treatments with muscle relaxants and a ketogenic diet. Intramuscular
      botulinum toxin resulted in significant relief of dystonia.

PMID- 9767516
TI  - Pneumocystis carinii pneumonia: pitfalls of prophylaxis.
AB  - Pneumocystis carinii pneumonia (PCP) occurs commonly in immunocompromised
      patients. Sulfamethoxazole-trimethoprim (SMX-TMP) is effective prophylaxis,
      although PCP may still occur despite apparently adequate use. We report three
      cases of PCP which highlight some of the pitfalls of prophylaxis.

PMID- 9767518
TI  - History of motion sickness is predictive of childhood migraine.

PMID- 9767519
TI  - Hemodialysis access failure: a call to action.
AB  - Recent evidence suggests that the cost as well as the morbidity associated with
      the maintenance of hemodialysis access is increasing rapidly; currently, the cost
      exceeds 1 billion dollars and access related hospitalization accounts for 25% of
      all hospital admissions in the U.S.A. This increase in cost and morbidity has
      been associated with several epidemiological trends that may contribute to access
      failure. These include late patient referral to nephrologists and surgeons, late
      planning of vascular access as well as a shift from A-V fistulaes to PTFE grafts
      and temporary catheters, which have a higher failure rate. The reasons for this
      shift in the types of access is multifactorial and is not explained by changes in
      the co-morbidities of patients presenting to dialysis. Surgical preference and
      training also appear to play an important role in the large regional variation
      and patency rate of these PTFE grafts. We propose a program for early placement
      of A-V fistulae, a continuous quality improvement, multidisciplinary program to
      monitor access outcome, the development of new biomaterials, and a research plan
      to investigate pharmacological intervention to reduce development of stenosis and
      clinical interventions to treat those that do develop, prior to thrombosis.

PMID- 9767520
TI  - Aquaporins in the kidney: emerging new aspects.
AB  - Since 1992 and the discovery of an MIP (major intrinsic protein of lens fiber
      cell) homologue protein that selectively permeates water, aquaporin (AQP), there
      has been an explosion of research in this field. Early research speculated that
      aquaporins played indispensible physiological roles in bacteria and plants, as
      well as in mammalian organs such as red blood cells, kidney, eye, brain and lung,
      where water transport rapidly takes place. Yet human subjects were identified who
      lacked AQP1 and yet had no apparent phenotypical changes clinically. To date 10
      aquaporins have been discovered and a plethora of MIP members, and their
      prevalance in almost all organisms is a testament to their indispensible roles in
      the body, possibly as water and small neutral solute transporting channels. The
      recent localization of many different aquaporins in the same organ indicates that
      they may work cooperatively, which may partially explain the mystery of their
      physiological mechanism. Because the physiological roles of most aquaporins are
      currently only speculation, more extensive research is necessary to understand
      the exact function of each aquaporin.

PMID- 9767522
TI  - Selectivity of endotoxin-induced defect in endothelial calcium mobilization.
AB  - BACKGROUND: We hypothesized that endotoxin (LPS) would impair bradykinin (BK)
      induced calcium (Ca2+) mobilization in aortic endothelial cells, perhaps due to
      cytotoxicity or via stimulation of nitric oxide (NO) synthesis. As well, we
      sought to define contributions of LPS-stimulated Ca2+ mobilization to these
      effects. METHODS: LPS- or BK-induced increments of intracellular Ca2+ were
      assessed by microspectrofluorimetry with fura-2 in passaged bovine aortic
      endothelial cells. Time- and dose-dependent effects of LPS exposure (+/-
      inhibitors of NO or prostaglandin synthesis) on subsequent BK-induced Ca2+
      mobilization and on attached cell counts were determined. RESULTS: LPS (0.1 to
      1.0 mg/ml) led to rapid increments of Ca2+, while Ca2+ responses were delayed
      following LPS (1 to 10 microg/ml) and lower doses were without effect. By
      contrast, LPS more potently (1.0 pg to 1.0 microg/ml) led to dose- and time
      dependent impairment of subsequent BK-induced Ca2+ mobilization, with peak effect
      at four to six hours, persisting for at least 18 hours. This delayed effect on BK
      response was unaltered by inhibition of either NO synthase or cyclooxygenase. The
      effect of LPS on BK-responsivity depended importantly on cell confluence, as it
      was not observed in subconfluent cells. By contrast, LPS-induced cell detachment,
      which was observed only at doses > or = 1.0 microg/ml, did not depend on
      confluence. CONCLUSIONS: Different mechanisms lead to endothelial cytotoxicity
      and to impaired BK-response following LPS. Only the former effect, occurring at
      higher doses, might depend on initial LPS-induced Ca2+ mobilization.

PMID- 9767521
TI  - Renal expression of transforming growth factor-beta inducible gene-h3 (beta ig
      h3) in normal and diabetic rats.
AB  - BACKGROUND: Transforming growth factor-beta (TGF-beta) has been implicated in the
      pathogenesis of a number of kidney diseases characterized by glomerulosclerosis
      and tubulointerstitial fibrosis. TGF-beta is secreted in a latent form requiring
      extracellular modification to become biologically active. TGF-beta inducible gene
      h3 (beta ig-h3) is a recently identified TGF-beta-induced gene product. The
      present study sought to examine beta ig-h3 expression in normal and diabetic
      rats. METHODS: Beta ig-h3, TGF-beta1 and alpha1 (IV) collagen gene expression
      were assessed by Northern blot analysis and in situ hybridization in 20 Sprague
      Dawley rats, randomly assigned to receive streptozotocin (diabetic, N = 11) or
      citrate buffer alone (control, N = 9) and sacrificed eight months later. The
      effect of exogenous TGF-beta1 on beta ig-h3 expression was also assessed in
      cultured proximal tubular cells. RESULTS: In situ hybridization localized beta ig
      h3 gene expression to the juxtaglomerular apparatus and the pars recta (S3
      segment) of proximal tubules in both control and diabetic animals. Kidney TGF
      beta 1, beta ig-h3 and alpha1 (IV) collagen mRNA from diabetic rats were
      increased two- to threefold compared with controls (P < 0.01). There was a
      significant correlation between TGF-beta1 and beta ig-h3 gene expression in
      kidneys from diabetic rats (r = 0.73, P = 0.01). In addition, beta ig-h3 mRNA
      increased in response to exogenous TGF-beta1 in a dose-dependent fashion in
      cultured proximal tubular cells. CONCLUSION: These findings support the
      hypothesis that biologically active TGF-beta plays a pathogenetic role in
      diabetic kidney disease and suggest that beta ig-h3 may be a useful index of TGF
      beta1 bioactivity in the kidney.

PMID- 9767524
TI  - Serotonin enhances the production of type IV collagen by human mesangial cells.
AB  - BACKGROUND: The plasma concentration of 5-hydroxytryptamine (5-HT) in diabetic
      patients is higher than that in normal subjects. Since recent reports have
      demonstrated the presence of 5-HT2A receptor in glomerular mesangial cells, it is
      possible that 5-HT may be involved in the development of diabetic nephropathy
      through the 5-HT2A receptor in mesangial cells. Because expansion of the
      glomerular mesangial lesion is a characteristic feature of diabetic nephropathy,
      we examined the effect of 5-HT on the production of type IV collagen by human
      mesangial cells. METHODS: Human mesangial cells were incubated with 5-HT with or
      without 5-HT receptor antagonists, protein kinase C (PKC) inhibitor or
      transforming growth factor-beta (TGF-beta) antibody. Type IV collagen mRNA and
      protein concentration in medium were measured by Northern blot analysis and
      enzyme-linked immunosorbent assay (ELISA), respectively. TGF-beta mRNA and
      bioactivity in the medium were measured by Northern blot analysis and bioassay
      using mink lung epithelial cells, respectively. RESULTS: 5-HT stimulated the
      production of type IV collagen by human mesangial cells, which was inhibited by
      ketanserin and sarpogrelate hydrochloride, 5-HT2A receptor antagonists, but not
      by ondansetron, a 5-HT3 receptor antagonist. 5-HT increased the bioactivities of
      both active and total TGF-beta. However, the 5-HT-enhanced production of type IV
      collagen was completely inhibited by an anti-TGF-beta antibody. Furthermore, a
      PKC inhibitor, calphostin C, inhibited the 5-HT-induced increase in type IV
      collagen secretion, and the activity of membrane PKC was increased by 5-HT.
      Phorbol ester activated type IV collagen production as well as active and total
      TGF-beta. Calphostin C completely inhibited the 5-HT-enhanced activity of active
      TGF-beta, but did not inhibit exogenous TGF-beta-induced increase in type IV
      collagen secretion. CONCLUSIONS: Our results suggest that 5-HT-enhanced
      production of type IV collagen by human mesangial cells is mediated by activation
      of PKC and subsequent increase in active TGF-beta activity.

PMID- 9767523
TI  - IGF-I binding proteins, IGF-I binding protein mRNA and IGF-I receptor mRNA in
      rats with acute renal failure given IGF-I.
AB  - BACKGROUND: Recombinant human insulin-like growth factor-I (rhIGF-I) accelerates
      recovery from acute renal failure (ARF) in rats. IGF-I acts through the IGF-I
      receptor (IGF-IR) and its actions may be modified by IGF-I binding proteins
      (IGFBPs). It therefore would be of value to determine the effects of both ARF and
      rhIGF-I treatment on serum IGFBPs and mRNA for IGFBPs and IGF-IR. METHODS: Rats
      with ARF and sham-operated control rats were randomized to receive rhIGF-I or
      vehicle injections thrice daily for 72 to 74 hours starting five hours after
      surgery. Serum IGFPBs 1 to 6 were measured serially, and mRNA for IGFBPs 1 to 6
      and for IGF-IR were measured in several tissues obtained 72 to 74 hours after
      surgery. RESULTS: At 72 to 74 hours, serum IGFBP-1 and IGFBP-2 levels were higher
      in rhIGF-I treated rats. Serum IGFBP-3 was affected by both ARF and rhIGF-I.
      IGFBP-4 rose transiently only in ARF groups. At 72 to 74 hours, mRNA for several
      IGFBPs was reduced in renal cortex of ARF rats. Low mRNA for IGFBP-4 and -6 was
      observed in renal medulla of the ARF rats, particularly in comparison to the sham
      operated rats receiving vehicle. Renal medullary IGFBP-2 mRNA was decreased in
      ARF and sham rats given rhIGF-I as compared to sham animals given vehicle.
      Hepatic IGFBP-2 mRNA was higher in both rhIGF-I treated groups versus those given
      vehicle. Otherwise, there were no differences in IGFBP mRNAs among the four
      groups in lung, heart, and skeletal muscle. IGF-IR mRNA was decreased in renal
      cortex and medulla of both ARF groups and was not detected in liver in any group.
      CONCLUSIONS: Thus, ARF and rhIGF-I treatment each affected certain serum IGFBPs
      and jointly affected some IGFBPs. ARF suppressed gene transcription for renal
      cortical and medullary IGF-IR and some IGFBPs. rhIGF-I independently affected
      some renal cortical or medullary IGFBP mRNAs. rhIGF-I increased hepatic IGFBP-2
      mRNA and serum IGFBP-2. These effects of ARF or rhIGF-I may influence rhIGF-I
      actions in rats with ischemic ARF.

PMID- 9767525
TI  - Shiga toxin-1 regulation of cytokine production by human proximal tubule cells.
AB  - BACKGROUND: Interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor
      (TNF) levels are elevated in kidneys of patients with post-diarrheal hemolytic
      uremic syndrome (D+HUS) and may contribute to renal dysfunction. The renal
      cellular sources of these inflammatory cytokines in D+HUS are largely unknown,
      however, the proximal tubule has emerged as a potentially important candidate.
      Since Shiga toxin-1 (Stx-1) has been implicated in the genesis of D+HUS, we
      examined the effect of Stx-1 on cytokine production by human proximal tubule
      cells. METHODS: Stx-1 cytotoxicity, protein synthesis inhibition, and effect on
      IL-1, IL-6, and TNF protein release and mRNA levels were determined. The effect
      of another protein synthesis inhibitor, cycloheximide (CHX), on these parameters
      was also evaluated. RESULTS: Stx-1 greatly increased TNF release and mRNA levels
      while CHX, at concentrations that produced similar inhibition of protein
      synthesis, had no effect on TNF production. In contrast, Stx-1 and CHX caused
      comparable elevations in IL-1 release and mRNA accumulation. Stx-1 and CHX also
      stimulated IL-6 mRNA accumulation, but only at concentrations that either were
      cytotoxic or substantially blocked protein synthesis. Finally,
      lipopolysaccharide, which is likely to be elevated in the circulation of patients
      with D+HUS, had no effect alone, but synergized with Stx-1 to increase IL-1
      production. CONCLUSIONS: These results indicate that Stx-1 stimulates proximal
      tubule inflammatory cytokine production and that this effect is due partially to
      nonspecific induction of mRNA levels as well as activation of Stx-1-specific
      mechanisms.

PMID- 9767526
TI  - Transcriptional activation of transforming growth factor-beta1 in mesangial cell
      culture by high glucose concentration.
AB  - BACKGROUND: Transforming growth factor-beta (TGF-beta) is an important
      hypertrophic and prosclerotic cytokine in the pathogenesis of diabetic
      nephropathy. The mechanisms of regulation of the TGF-beta system by high ambient
      glucose in kidney cells are incompletely defined. This study examined the
      mechanisms of regulation of TGF-beta1 expression by high glucose in murine
      mesangial cells (MMCs) in culture. METHODS: MMCs were cultured in either normal
      (100 mg/dl) or high (450 mg/dl) D-glucose concentration. Total TGF-beta1 protein
      secretion and bioactivity, mRNA expression and stability, and gene transcription
      rate were measured; promoter-reporter chloramphenicol acetyltransferase (CAT)
      assays and electrophoretic mobility shift assay (EMSA) were performed to
      investigate the presence of putative glucose-response elements. RESULTS: Raising
      the ambient D-glucose concentration for 72 hours increased TGF-beta1 bioactivity
      in cell culture medium by 47% and total TGF-beta1 secretion by approximately 90%.
      Northern analysis demonstrated that the steady-state TGF-beta1 mRNA level was
      increased nearly twofold after 48 hours of growth in high glucose. This increase
      was not due to increased stability, as the half-life of the message was
      approximately five hours in both normal and high glucose conditions.
      Transcriptional activity of the TGF-beta1 gene (nuclear run-on assay) was
      increased by 73% in cells grown in high glucose for 24 hours. Transiently
      transfected MMCs with CAT constructs containing varying lengths of the murine TGF
      beta1 promoter demonstrated that high glucose selectively increased the
      expression of only one of the constructs, pA835. Sequence inspection revealed the
      presence of a putative glucose responsive element, CACGTG, within this construct.
      High glucose in MMC culture for 24 hours increased nuclear protein binding to a
      probe containing this element when analyzed using EMSA. CONCLUSIONS: High glucose
      stimulates total TGF-beta1 protein production and bioactivity as well as the
      steady-state level of TGF-beta1 mRNA. The latter effect is due primarily to
      stimulation of gene transcription rate rather than message stability.
      Transcriptional activation by high glucose may involve a region in the TGF-beta1
      promoter containing a putative glucose-response element.

PMID- 9767527
TI  - Shiga toxin 1 elicits diverse biologic responses in mesangial cells.
AB  - BACKGROUND: Shiga toxin 1 (Stx1) is a causative agent in hemolytic uremic
      syndrome (HUS). Its receptor, the glycosphingolipid globotriaosylceramide (Gb3),
      is expressed on cultured human endothelial and mesangial cells. Mesangial cell
      injury in HUS ranges from mild cellular edema to severe mesangiolysis and
      eventual glomerulosclerosis. We hypothesized that, in addition to endothelial
      cells, mesangial cells are targets of Stx1. METHODS: Human mesangial cells were
      exposed to Stx1. Protein synthesis was measured using [35S]-methionine/cysteine.
      Cell viability was measured as the lysosomal uptake of Neutral Red. Monocyte
      chemotactic peptide (MCP-1) mRNA and protein were analyzed by Northern blotting
      and ELISA. RESULTS: Stx1 (0.25 to 2500 ng/ml) resulted in a dose-dependent
      inhibition of protein synthesis. This effect of Stx1 was potentiated by
      preincubation of the cells with interleukin-1alpha (IL-1alpha; 2 ng/ml) or tumor
      necrosis-alpha (TNF-alpha; 500 U/ml). Stx1 had little effect on mesangial cell
      viability during the first 24 hours of exposure to Stx1. However, prolonged
      incubation with Stx1 for 48 and 72 hours resulted in a 68% and 80% decrease in
      cell-viability, respectively. Stx1 elicited a dose and time dependent increase in
      the levels of MCP-1 mRNA, an effect that was potentiated by preincubation with IL
      1alpha. CONCLUSION: These data indicate that mesangial cells are susceptible to
      the effects of Stx1 in vitro. Stx1 exerts a spectrum of biologic effects on
      mesangial cells ranging from activation of chemokine genes to a lethal toxic
      injury. Immunoinflammatory cytokines potentiate the effects of Stx1. Thus,
      glomerular pathology in HUS may also result from a direct effect of Stx1 on
      mesangial cells.

PMID- 9767528
TI  - Potential role of hepatocyte growth factor in the maintenance of renal structure:
      anti-apoptotic action of HGF on epithelial cells.
AB  - BACKGROUND: Mesangial cells (MC) are known to secrete various vasoactive
      substances that may control endothelial and epithelial cell growth. Therefore,
      the cell-cell interactions among these cells may be important in the control of
      renal function. However, the exact mechanisms of maintaining the cell-cell
      interactions are not yet understood. We have focused on the role of hepatocyte
      growth factor (HGF) in the regulation of cell-cell interactions, since HGF has
      many protective functions in the kidney. To investigate the role of HGF in renal
      injury, we examined (1) the effects of HGF on epithelial injury induced by serum
      deprivation, and (2) the role of local HGF production in the maintenance of renal
      structure. METHODS: Apoptotic changes in epithelial cells were assessed by
      nuclear morphology and DNA fragmentation assay. Transfection of human HGF vector
      into epithelial cells was performed by a highly efficient viral-liposome method.
      The effects of secreted HGF on the growth of renal cells were examined using a co
      culture system. RESULTS: The addition of recombinant HGF (rHGF) stimulated the
      growth of rat and porcine epithelial cells. Moreover, the decrease in number of
      epithelial cells by serum deprivation was significantly attenuated by rHGF.
      Interestingly, apoptotic changes in epithelial cells induced by serum deprivation
      were also significantly attenuated by rHGF (P < 0.01). As a model of gene
      therapy, the effects of overexpression of human HGF gene in epithelial cells on
      apoptosis induced by serum deprivation were examined. Transfection of human HGF
      vector into epithelial cells also attenuated epithelial cell death induced by
      serum deprivation through the inhibition of apoptosis, accompanied by increased
      HGF production (P < 0.01). In addition, HGF also prevented endothelial injury
      induced by tumor necrosis factor-alpha and dexamethasone. Given the presence of a
      local HGF system, we measured local HGF secreted from renal cells. Immunoreactive
      HGF was observed in the conditioned medium of MC, but not epithelial cells, while
      the specific receptor of HGF, c-met, was expressed in epithelial cells. Of
      importance, co-culture of MC with epithelial cells resulted in a significant
      increase in number of epithelial cells, which was significantly abolished by
      neutralizing anti-HGF antibody. CONCLUSIONS: Overall, these results demonstrate
      that local production of HGF in MC may maintain the growth of epithelial and
      endothelial cells through its anti-apoptotic action.

PMID- 9767529
TI  - Therapeutic concentrations of cyclosporine A, but not FK506, increase P
      glycoprotein expression in endothelial and renal tubule cells.
AB  - BACKGROUND: The immunosuppressive drugs cyclosporine A (CsA) and tacrolimus
      (FK506) are extruded from cells by the multidrug resistance P-glycoprotein (P
      gp), an efflux pump for drugs and xenobiotics, which may limit their therapeutic
      effectiveness and/or incidence of toxic side effects. In the present study, we
      investigated the effect of therapeutic concentrations of CsA and FK506 on the
      expression of P-gp in cultured endothelial and proximal tubule cells. METHODS: P
      gp expression in human arterial endothelial (HAEC) and rat proximal tubule cells
      (RPTC) was determined by immunoblotting and immunocytochemistry, and correlated
      with P-gp-mediated transport by measuring the intracellular accumulation of the
      fluorescent probe calcein. RESULTS: Following incubation of HAEC with therapeutic
      concentrations of 0.1 to 1.6 microM CsA up to seven days, P-gp expression
      increased in a time- and concentration-dependent manner, maximally to 291 +/- 42%
      of controls with 0.8 microM CsA for seven days. Similar effects of CsA were
      observed in RPTC. In contrast, therapeutic concentrations of FK506 (0.01 to 0.2
      microM up to 7 days) did not change P-gp expression in either cell type, though
      at higher, supratherapeutic concentrations of FK506 (0.6 to 1.2 microM) P-gp
      expression was also increased. Immunocytochemistry revealed increased P-gp
      expression in the plasma membrane of HAEC and RPTC treated with 0.8 microM CsA,
      which was reflected by a decrease of P-gp-mediated accumulation of calcein in
      both cell types. CONCLUSIONS: The data suggest that the induction of P-gp
      expression in HAEC and RPTC at concentrations of CsA or FK506 above 0.5 microM is
      part of the protective answer of cells to toxic concentrations of the drugs and
      could therefore interfere with the therapeutic effectiveness of CsA in vivo.

PMID- 9767530
TI  - Dietary salt regulates expression of Tamm-Horsfall glycoprotein in rats.
AB  - BACKGROUND: Tamm-Horsfall glycoprotein (THP) is a unique protein that is produced
      exclusively by cells of the thick ascending limb of Henle's loop (TALH). This
      study examined whether dietary salt altered renal THP production. METHODS: Male
      Sprague-Dawley rats were examined on days 1, 4, and 15 following placement in
      metabolic cages on diet that contained 0.3%, 1.0% or 8.0% NaCl. THP expression
      was quantified using Northern hybridization and Western blotting analysis.
      RESULTS: An increase in dietary salt produced sustained increases in relative
      steady-state mRNA and protein levels of THP in the kidney. Addition of
      furosemide, but not chlorothiazide, to animals on the 8.0% NaCl diet further
      augmented steady-state mRNA levels of THP. CONCLUSIONS: An increase in dietary
      salt and the loop diuretic, furosemide, increased expression of THP in the rat.
      The data support the involvement of this unique protein in the function of the
      TALH during changes in dietary salt. These findings also suggest that restriction
      of dietary salt may be beneficial in cast nephropathy in multiple myeloma and
      recurrent nephrolithiasis, two diseases in which THP can play an important
      pathogenetic role.

PMID- 9767531
TI  - Contribution of tubular injury to loss of remnant kidney function.
AB  - BACKGROUND: The remnant kidney model has been widely used to identify mechanisms
      responsible for the progression of renal disease. However, the structural changes
      associated with progressive loss of function in this model have not been well
      characterized. METHODS: Kidney function and structure were assessed at 10 weeks
      (REM 10) and 25 weeks (REM 25) after five-sixths renal ablation and in control
      rats (Control). Serial sections were examined to relate glomerular and tubular
      structure in individual nephrons. RESULTS: Remnant kidney function declined
      between 10 and 25 weeks after ablation (GFR 0.90 +/- 0.34 vs. 0.23 +/- 0.07
      ml/min, REM 10 vs. REM 25, P < 0.05). This decline in function was associated
      with an increase in the prevalence of globally sclerotic glomeruli (14 +/- 10 vs.
      0 +/- 0 vs. 0 +/- 0%, REM 25 vs. REM 10 vs. Control, P < 0.05 REM 25 vs. REM 10
      and Control). The decline in remnant kidney function between 10 and 25 weeks was
      also associated with the appearance of glomeruli that were atubular (48 +/- 14
      vs. 9 +/- 8 vs. 3 +/- 5%, REM 25 vs. REM 10 vs. Control, P < 0.05 REM 25 vs. REM
      10 and Control) or connected to atrophic proximal tubule segments (26 +/- 10 vs.
      11 +/- 6 vs. 1 +/- 2%, REM 25 vs. REM 10 vs. Control, P < 0.05 all comparisons).
      Atubular glomeruli, which usually had open capillary loops available for
      filtration, were more numerous than globally sclerotic glomeruli at 25 weeks
      after ablation. CONCLUSIONS: These findings indicate that tubular injury
      contributes to progressive loss of renal function following reduction in nephron
      number.

PMID- 9767532
TI  - Distinct contribution of Fc receptors and angiotensin II-dependent pathways in
      anti-GBM glomerulonephritis.
AB  - BACKGROUND: The contribution of antibody and/or immune-complex to the
      pathogenesis of immunologically-mediated glomerulonephritis is not fully
      understood, although it has been recently clarified that Fc receptors (FcRs) play
      critical roles in the inflammatory cascade. We therefore re-evaluated the
      classical model of glomerulonephritis, anti-glomerular basement membrane antibody
      induced glomerulonephritis (Anti-GBM GN), from the standpoint of FcRs and also
      investigated the residual FcR-independent mechanisms. METHODS: We adopted an Anti
      GBM GN mouse model that has two strains deficient in the FcR gamma chain [gamma(
      /-)] or Fc gammaRIIB [RII(-/-)], and analyzed functional (urinary protein, serum
      creatinine, BUN) and pathological changes of the glomeruli. For the analyses of
      FcR-independent mechanisms, several doses of nephrotoxic serum were applied, and
      then mice were treated either with cobra venom factor or an angiotensin II type 1
      receptor antagonist in gamma(-/-) mice. RESULTS: In gamma(-/-) mice, renal
      injuries were dramatically attenuated with an absence of polymorphonuclear cell
      (PMN) influx, while RII(-/-) mice suffered accelerated glomerular injuries in
      spite of a normal PMN influx. In the absence of FcR-dependent effects in gamma(-/
      ) mice, the FcR-independent pathway lead to chronic renal damage characterized by
      mesangial proliferation and progressive expansion of mesangial area, with
      monocyte/macrophage accumulation and with the expression of alpha smooth muscle
      actin in the mesangial cells and interstitium. Those injuries in gamma(-/-) mice
      were not attenuated by the decomplementation, but completely abolished by using
      an angiotensin II type 1 receptor antagonist. CONCLUSIONS: Our results clearly
      demonstrate that FcRs play a pivotal role in Anti-GBM GN, especially in its acute
      phase. We further clarified the existence of FcR and complement-independent but
      antibody-dependent pathway. Furthermore, we found that those pathological changes
      were strongly related to the renin-angiotensin system.

PMID- 9767534
TI  - Regulation of survival and death of mesangial cells by extracellular matrix.
AB  - BACKGROUND: Cell-matrix interactions exert major effects on such phenotypic
      features as cell growth and differentiation. Apoptosis is an active form of cell
      death that is crucial for maintaining the appropriate number of cells as well as
      the organization of tissue. Recently, it has been suggested that apoptosis of the
      mesangial cells (MC) is important in glomerular remodeling after injury. The MC
      are surrounded by an extracellular matrix (ECM) in vivo. Since in disease
      conditions the mesangial matrix is altered quantitatively and qualitatively, it
      is of interest to determine whether cell-matrix interactions may influence
      apoptosis of the MC. METHODS: We first investigated the differences in the
      susceptibility to apoptotic stimuli of the MC cultured on various ECM components
      (type I collagen, fibronectin, basement membrane matrix). We then determined
      whether the inhibition of MC-matrix interactions would affect apoptosis. Finally,
      interactions between MC and matrix were disrupted by the inhibition of beta1
      integrin expression with antisense oligonucleotides (ODN). RESULTS: When MC were
      cultured on type I collagen or fibronectin and deprived of serum for eight hours,
      the extracted DNA from the MC demonstrated an internucleosomal ladder pattern on
      gel electrophoresis that constituted the biochemical characteristic of apoptosis.
      However, no ladder pattern was apparent when MC were cultured on basement
      membrane matrix. The attachment of cells was completely inhibited when the MC
      were cultured on agarose-coated dishes for 24 hours. Gel electrophoresis of DNA
      extracted from these cells showed a ladder pattern. However, the MC attached to
      the substratum did not show any apoptosis. MC showed an increase in apoptotic
      cell death after treatment with antisense ODN against beta1-integrin molecule.
      CONCLUSIONS: These results indicate that normal ECM may prevent the MC from
      undergoing apoptosis and serve as a survival factor for MC. Signals from ECM that
      prevent apoptosis may be mediated by beta1-integrin molecules.

PMID- 9767533
TI  - Regulation of smooth muscle alpha-actin expression and hypertrophy in cultured
      mesangial cells.
AB  - BACKGROUND: Mesangial cells during embryonic development and glomerular disease
      express smooth muscle alpha-actin (alpha-SMA). We were therefore surprised when
      cultured mesangial cells deprived of serum markedly increased expression of alpha
      SMA. Serum-deprived mesangial cells appeared larger than serum-fed mesangial
      cells. We hypothesized that alpha-SMA expression may be more reflective of
      mesangial cell hypertrophy than hyperplasia. METHODS: Human mesangial cells were
      cultured in medium alone or with fetal bovine serum, thrombin, platelet-derived
      growth factor-BB (PDGF-BB) and/or transforming growth factor-beta1 (TGF-beta1).
      Alpha-SMA expression was examined by immunofluorescence, Western blot, and
      Northern blot analysis. Cell size was analyzed by forward light scatter flow
      cytometry. RESULTS: Alpha-SMA mRNA was at least tenfold more abundant after three
      to five days in human mesangial cells plated without serum, but beta-actin mRNA
      was unchanged. Serum-deprived cells contained 5.3-fold more alpha-SMA after three
      days and 56-fold more after five days by Western blot. Serum deprivation also
      increased alpha-SMA in rat and mouse mesangial cells. The effects of serum
      deprivation on alpha-SMA expression were reversible. Mesangial cell mitogens,
      thrombin or PDGF-BB, decreased alpha-SMA, but TGF-beta1 increased alpha-SMA
      expression and slowed mesangial cell proliferation in serum-plus medium. Flow
      cytometry showed that serum deprivation or TGF-beta1 treatment caused mesangial
      cell hypertrophy. PDGF-BB, thrombin, or thrombin receptor-activating peptide
      blocked hypertrophy in response to serum deprivation. CONCLUSIONS: We conclude
      that increased alpha-SMA expression in mesangial cells reflects cellular
      hypertrophy rather than hyperplasia.

PMID- 9767535
TI  - Measurement of the kinetics of protein uptake by proximal tubular cells using an
      optical biosensor.
AB  - BACKGROUND: The affinity and specificity of protein reabsorption by proximal
      tubular cells have been investigated using techniques for monitoring endocytosis,
      demonstrating a high capacity but low affinity process. It is not known whether
      uptake is through binding to a single binding site/receptor with differing
      affinities, or if there are several classes of binding sites receptors, each
      specific for differing proteins or groups, such as, high or low molecular weight
      proteins. METHODS: We have developed a novel technique for analyzing the kinetics
      of protein binding to tubular cells using a optical biosensor system. We have
      studied the binding of cultured LLCPK cells to albumin and RBP immobilized onto
      the sensor. By adding increasing concentrations of competing proteins [varying in
      molecular weight from 66,000 to 11,800 D and pI from 4.6 to 9.2 as represented by
      albumin, alpha1-microglobulin (alpha1M), retinol binding protein (RBP), cystatin
      C and beta2-microglobulin (beta2m)], specific and inhibitable cell binding was
      demonstrated. RESULTS: Equilibrium constants, KA, could be calculated from the
      reciprocal of the protein concentration causing 50% inhibition in binding rate.
      These were: albumin = 8.0 x 10(4) M(-1), alpha1M = 2.0 x 10(5) M(-1), RBP = 2.7 x
      10(4) M(-1), cystatin C = 2.0 x 10(4) M(-1), beta2m = 4.2 x 10(3) M(-1). There
      were no significant differences between the measured KA's whether RBP or albumin
      were immobilized on the surface. CONCLUSIONS: All the proteins gave similar
      shaped inhibition profiles, suggesting that there is one binding site/receptor
      for all proteins studied, regardless of molecular weight or charge, but there are
      differing affinities for each protein.

PMID- 9767536
TI  - Mechanisms through which high glucose concentration raises [Ca2+]i in renal
      proximal tubular cells.
AB  - BACKGROUND: The basal levels of cytosolic calcium ([Ca2+]i) of renal proximal
      tubular cells of rats with streptozotocin-induced diabetes are elevated. It is
      possible that this phenomenon is mediated by the hyperglycemia, which may cause
      both increased calcium influx into and/or decreased calcium efflux out of these
      cells. METHODS: We examined whether high glucose concentration in vitro causes
      acute rise in [Ca2+]i of freshly isolated renal proximal tubular cells and
      explored the pathways that are involved in such an event. RESULTS: There were
      dose and time dependent increments in [Ca2+]i of renal proximal tubular cells
      exposed to high concentrations of glucose. A similar effect was observed with
      equimolar concentrations of mannitol or choline chloride but not urea. A
      substantial part of the rise in [Ca2+]i was inhibited when the media contained
      verapamil, nifedipine, amlodipine or ryanodine and when the cells were placed in
      a calcium free media. Inhibitors of G protein(s) (GDPbetaS or pertussis toxin),
      inhibitors of cAMP-protein kinase A pathway (RpcAMP or H-89), inhibitors of
      protein kinase C (staurosporine or calphostin) and inhibitor of Na+-H+ exchanger
      (HOE 694) blocked the rise in a dose dependent manner. High glucose concentration
      also caused a decrease in ATP content of these cells and a reduction in the Vmax
      of their Ca2+ATPase. CONCLUSIONS: The results are consistent with the formulation
      that the osmotic activity (cell shrinkage) of the high glucose concentration may
      activate a stretch receptor with subsequent stimulation of various cellular
      pathways including G protein(s), cAMP-protein kinase A and phospholipase C
      systems and calcium channels. Activation of these cellular pathways permits both
      calcium influx into renal tubular cells and mobilization of calcium from their
      intracellular stores. Further, a decrease in calcium efflux secondary to the
      reduction in the Vmax of Ca2+ ATPase may occur. It is possible that the rise in
      [Ca2+]i is critical for the stimulation of the events that lead to restoration of
      cell volume to normal.

PMID- 9767537
TI  - Localization of the ROMK potassium channel to the apical membrane of distal
      nephron in rat kidney.
AB  - BACKGROUND: The apical potassium (K+) channels mediate K+ recycling in thick
      ascending limb (TAL) and K+ secretion in cortical collecting duct (CCD).
      Recently, the cDNAs for a family of renal K+ channels, ROMK1, -2 and -3, were
      identified. Based on the biophysical properties and mRNA distribution, it is
      believed that these ROMK cDNAs encode the apical K+ channels of TAL and CCD.
      However, the information for cellular and subcellular localization of the ROMK
      proteins in these tubules is still not available. METHODS: Paraffin or frozen
      kidney sections from adult Sprague-Dawley rats were stained by polyclonal
      antibodies against the N- and C-terminal domain of ROMK. Immunoreactive staining
      was visualized by color development from horseradish peroxidase reaction.
      Membrane homogenates from kidney were analyzed by Western blot analysis. RESULTS:
      The polyclonal antibodies against cytoplasmic epitope of ROMK recognized a
      approximately 42 kD protein in the membrane homogenates from kidney, but not from
      liver. Staining by immunocytochemistry revealed that ROMK channels were localized
      to the apical membranes of the distal nephron in cortex and outer medulla,
      including thick ascending limb and collecting tubule. ROMK staining was absent in
      glomerulus, proximal tubule and inner medulla. Double staining of the tissue
      section with both ROMK-specific and H+-ATPase-specific antibodies revealed
      labeling of ROMK in the principal cells of the collecting tubules. CONCLUSIONS:
      These results further strengthen the idea that ROMK channels play important roles
      in the recycling of K+ in TAL and the secretion of K+ in CCD.

PMID- 9767538
TI  - Parathyroid hormone and dietary phosphate provoke a lysosomal routing of the
      proximal tubular Na/Pi-cotransporter type II.
AB  - BACKGROUND: A decrease of proximal tubular reabsorption of phosphate (Pi), which
      can be provoked by parathyroid hormone (PTH) or by a high Pi-diet, has been shown
      to correlate with a decrease of the number of type II Na/Pi-cotransporters
      residing in the brush border membrane. While both PTH and a high Pi-diet lead to
      an internalization of type II cotransporters, the further cellular routing of
      internalized cotransporters has not been established unequivocally. METHODS: To
      prevent lysosomal degradation, rats were treated with leupeptin prior to the
      injection of PTH or feeding acutely with a high Pi-diet. Kidney cortex were
      recovered and used for immunohistochemistry. In parallel, brush border membranes
      and lysosomes were isolated and analyzed by Western blotting. RESULTS: Under both
      conditions (PTH and high Pi-diet), a strong overlap of internalized type II
      cotransporters with the late endosomes/lysosomes was observed by
      immunohistochemistry. In agreement, the content of type II Na/Pi-cotransporters
      was increased in lysosomes isolated from the corresponding tissues. CONCLUSIONS:
      These results suggest that in proximal tubular cells type II Na/Pi-cotransporters
      internalized due to the action of PTH and acute high Pi-diet are routed to the
      lysosomes, and likely do not enter a recycling compartment.

PMID- 9767539
TI  - Colonic H+-K+-ATPase is induced and mediates increased HCO3- reabsorption in
      inner medullary collecting duct in potassium depletion.
AB  - BACKGROUND: Potassium depletion increases HCO3- reabsorption in outer medullary
      collecting duct (OMCD) by activation of colonic (c) H-K-ATPase (HKA). The purpose
      of the current experiments was to examine the role of the isoforms of HKA in HCO3
      reabsorption by terminal inner medullary collecting duct (IMCD) cells in
      potassium depletion. METHODS: Sprague-Dawley rats were fed a potassium-free diet
      and studied after 8 to 10 days. mRNA expression of HKA isoforms in terminal
      portion of inner medulla was examined and correlated with HCO3- reabsorption in
      the terminal IMCD. RESULTS: Gastric (g) HKA mRNA decreased whereas colonic (c)
      HKA mRNA expression was heavily induced in terminal portion of inner medulla in
      potassium depleted rats. Net HCO3- flux (JtCO2) in terminal IMCD increased in
      potassium depletion (4.56 to 7.06 pmol/min/mm tubule length, P < 0.001). In
      normal rats, 1 mM ouabain in perfusate had no effect on JtCO2, whereas 10 microM
      Schering 28080 (SCH) decreased JtCO2 to 2.4 (P < 0.002). In KD rats, 1 mM ouabain
      decreased JtCO2 to 4.9 (P < 0.005) and 10 microM SCH decreased JtCO2 to 3.3 (P <
      0.001). However, the inhibitory effects of SCH and ouabain on JtCO2 in potassium
      depleted animals were not additive. CONCLUSIONS: The data indicate that gHKA is
      suppressed whereas cHKA is induced in potassium depletion and mediates increased
      HCO3- reabsorption in terminal IMCD. The results further indicate that cHKA in
      vivo is sensitive to both SCH and ouabain.

PMID- 9767540
TI  - Nature of glomerular dysfunction in pre-eclampsia.
AB  - BACKGROUND: Pre-eclampsia is characterized by hypertension, proteinuria and
      edema. Simultaneous studies of kidney function and structure have not been
      reported. We wished to explore the degree and nature of glomerular dysfunction in
      pre-eclampsia. METHODS: Physiologic techniques were used to estimate glomerular
      filtration rate (GFR), renal plasma flow and afferent oncotic pressure
      immediately after delivery in consecutive patients with pre-eclampsia (PET; N =
      13). Healthy mothers completing an uncomplicated pregnancy served as functional
      controls (N = 12). A morphometric analysis of glomeruli obtained by biopsy and
      mathematical modeling were used to estimate the glomerular ultrafiltration
      coefficient (Kf). Glomeruli from healthy female kidney transplant donors served
      as structural controls (N = 8). RESULTS: The GFR in PET was depressed below the
      control level, 91 +/- 23 versus 149 +/- 34 ml/min/1.73 m2, respectively (P <
      0.0001). In contrast, renal plasma flow and oncotic pressure were similar in the
      two groups (P = NS). A reduction in the density and size of endothelial fenestrae
      and subendothelial accumulation of fibrinoid deposits lowered glomerular
      hydraulic permeability in PET compared to controls, 1.81 versus 2.58 x 10(-9)
      m/sec/PA. Mesangial cell interposition also curtailed effective filtration
      surface area. Together, these changes lowered the computed single nephron Kf in
      PET below control, 4.26 versus 6.78 nl/min x mm Hg, respectively. CONCLUSION: The
      proportionate (approximately 40%) depression of Kf for single nephrons and GFR
      suggests that hypofiltration in PET does not have a hemodynamic basis, but is a
      consequence of structural changes that lead to impairment of intrinsic glomerular
      ultrafiltration capacity.

PMID- 9767541
TI  - Adenovirus-mediated kallikrein gene delivery reverses salt-induced renal injury
      in Dahl salt-sensitive rats.
AB  - BACKGROUND: The tissue kallikrein-kinin system has been shown to play a role in
      cardiac and renal functions. In this study, we investigated the ability of
      kallikrein gene delivery to reverse salt-induced cardiac hypertrophy and renal
      injury in Dahl salt-sensitive rats. METHODS: Adenovirus harboring the human
      tissue kallikrein gene, Ad.CMV-cHK, was delivered intravenously into Dahl salt
      sensitive rats suffering from hypertension, cardiac hypertrophy and renal damage
      induced by a high salt diet (4% NaCl) for four weeks. RESULTS: Expression of
      human kallikrein mRNA was detected in rat kidney, heart, aorta and liver, and
      immunoreactive human kallikrein levels were measured in the serum and urine of
      rats receiving gene delivery. A single injection of Ad.CMV-cHK caused a
      significant reduction of blood pressure for more than two weeks. Kallikrein gene
      transfer caused left ventricular mass reduction and elevated glomerular
      filtration rate, renal blood flow, urinary excretion, urinary kinin,
      nitrite/nitrate content, cGMP and cAMP levels. Morphological investigations
      showed that kallikrein gene transfer caused a significant reversal in salt
      induced tissue and organ damage. In the heart, cardiac hypertrophy and fibrosis
      were reduced, and in the kidney, both glomerular sclerotic lesions and tubular
      damage were reversed. CONCLUSIONS: Adenovirus-mediated kallikrein gene delivery
      is effective in reversing salt-induced cardiac hypertrophy and renal injury in
      Dahl-salt sensitive rats.

PMID- 9767542
TI  - Peripheral microvascular parameters in the nephrotic syndrome.
AB  - BACKGROUND: Peripheral edema, in combination with severe proteinuria and low
      serum albumin levels, is pathognomonic of the nephrotic syndrome, yet the exact
      mechanism of its formation is unknown. Two of the most important of the factors
      in Starling's forces controlling fluid filtration across the capillary have
      hitherto not been studied in nephrotic subjects. METHODS: The hydrostatic
      capillary pressure at the finger nail-fold in actively nephrotic subjects and age
      and sex matched controls was studied, using direct puncture of the apex of the
      capillary under video microscopy, and a servonulling apparatus to give a direct
      measurement of capillary pressure. Capillary filtration capacity (CFC) at the
      calf was measured noninvasively by a modern derivative of the technique of
      mercury strain gauge plethysmography. Fifteen nephrotic subjects with a variety
      of underlying pathological lesions, and age matched controls were studied.
      RESULTS: Contrary to the assumption of the "overflow" hypothesis of edema
      formation, there was no evidence of capillary hypertension. The capillary
      pressure showed no difference between nephrotic subjects and controls: median
      (range) of 17.6 (12.0 to 24.2) compared with 17.3 (9.0 to 21.6) mm Hg, P = NS.
      CFC was significantly higher in nephrotic subjects than controls [5.23 (3.28 to
      8.52) x 10(-3) versus 3.55 (2.43 to 5.28) x 10(-3) ml/min/100 g/mm Hg, P < 0.01].
      CONCLUSIONS: An increase in CFC provides a potentially novel mechanism
      contributing at least in part to the formation of peripheral edema in the
      nephrotic syndrome.

PMID- 9767543
TI  - Low leptin gene expression and hyperleptinemia in chronic renal failure.
AB  - BACKGROUND: The ob gene product leptin is thought to be a key regulator of food
      intake and body weight. Patients having advanced chronic renal failure (CRF) have
      markedly higher serum leptin levels. It is not known whether the increase in
      leptin levels in CRF is caused by a decreased plasma clearance and/or increased
      production. METHODS: In the present study serum leptin levels and glomerular
      filtration rate (GFR) were measured in 219 patients having various degrees of
      renal failure. In addition, serum leptin levels, C-reactive protein (CRP), body
      composition (by dual-energy x-ray absorptiometry) and ob gene expression (by in
      situ hybridization histochemistry) were determined in 15 patients with advanced
      CRF. Seven of the patients were re-evaluated following 12 months of peritoneal
      dialysis (PD) treatment. RESULTS: Serum leptin levels correlated negatively to
      GFR (r = -0.26; P < 0.0001). The ob gene expression was significantly lower in
      patients with CRF than in healthy controls. A negative correlation between serum
      leptin levels and ob gene expression (r = -0.66; P < 0.05) was found in patients
      with CRP < 25 mg/liter. The ob gene expression (20.0 +/- 1.8 vs. 15.0 +/- 1.0
      nCi/g; P < 0.05) was significantly higher in 5 patients with CRP > 25 mg/liter
      than in 10 patients with CRP < 25 mg/liter. Following 12 months of PD, the amount
      of body fat increased by 30% while the ob gene expression remained unchanged.
      CONCLUSION: The present study shows a correlation between serum leptin levels and
      GFR, and our results suggest that elevated leptin levels, due to a decreased
      plasma clearance, down-regulate the expression of the ob gene. We also found that
      an ongoing inflammation stimulates ob gene expression in patients with CRF.
      Therefore, it is suggested that the hyperleptinemia induced feedback inhibition
      of ob gene expression is overcome by inflammatory cytokines.

PMID- 9767544
TI  - Circadian variations of renal sodium handling in patients with orthostatic
      hypotension.
AB  - BACKGROUND: Sodium wasting during the night has been postulated as a potential
      pathophysiological mechanism in patients suffering from orthostatic hypotension
      due to severe autonomic deficiency. METHODS: In this study, the diurnal
      variations in creatinine clearance, sodium excretion and segmental renal tubular
      handling of sodium were evaluated in 18 healthy subjects and 20 young patients
      with orthostatic hypotension (OH). In addition, 24-hour ambulatory blood pressure
      and the neuro-hormonal response to changes in posture were determined. The
      patients and their controls were studied on a free sodium intake. In a second
      protocol, 10 controls and 10 patients were similarly investigated after one week
      of a high salt diet (regular diet + 6 g NaCl/day). RESULTS: Our results
      demonstrate that, in contrast to normal subjects in whom no significant changes
      in glomerular filtration, sodium excretion and segmental sodium reabsorption were
      observed throughout the day, patients with OH were characterized by a significant
      increase in glomerular filtration rate during the nighttime (P = 0.03) and
      significant increases in urinary lithium excretion (P < 0.05) and lithium
      clearance (P = 0.05) during the night, suggesting a decreased proximal
      reabsorption of sodium. On a high sodium diet, the symptoms of orthostatic
      hypotension and the circadian variations in sodium reabsorption were
      significantly blunted. CONCLUSIONS: These results suggest that, while the patient
      is in a supine position the effective blood volume of those with OH becomes
      excessive due to the increased venous return. Hence, the kidney responds with an
      increase in glomerular filtration and a relative escape of sodium from the
      proximal tubular segments. These circadian variations in renal sodium handling
      may contribute to the maintenance of the orthostatic syndrome.

PMID- 9767545
TI  - Effects of an ACE inhibitor/calcium antagonist combination on proteinuria in
      diabetic nephropathy.
AB  - BACKGROUND: The degree of proteinuria in patients with diabetes correlates
      strongly with both an increase in progression of nephropathy as well as
      cardiovascular events. Moreover, post hoc analyses of recent clinical trials
      support the concept that reductions of blood pressure and proteinuria correlate
      with a slowed progression of nephropathy. Both angiotensin converting enzyme
      (ACE) inhibitors and the nondihydropyridine calcium antagonists, (non-DHPCAs)
      reduce both arterial pressure and proteinuria in those with diabetic nephropathy.
      METHODS: The present randomized, open label, parallel group designed study tests
      the hypothesis that, at similar levels of blood pressure, the combination of an
      ACE inhibitor, trandolapril (T) with the non-DHPCA, verapamil (V) produces a
      greater reduction in proteinuria over either agent alone at one year. Thirty
      seven participants, mean age 59.6 +/- 5.8 years, with nephropathy (baseline
      creatinine 1.4 +/- 0.3 mg/dl and proteinuria of 1342 +/- 284 mg/dl) secondary to
      type 2 diabetes completed the study. Doses of drug were titrated in each group
      over eight weeks to achieve a goal blood pressure of < 140/90 mm Hg. All
      participants were counseled to ingest a sodium diet of < 120 mEq/day. RESULTS:
      Proteinuria reduction from baseline was significantly greater in the T+V group
      compared to either T alone (-33 +/- 8%, T vs. -62 +/- 10%, T+V; P < 0.001) or V
      alone (-27 +/- 8%, V vs. -62 +/- 10%, T+V; P < 0.001). No significant differences
      in either glomerular filtration rate, arterial pressure, fasting blood glucose or
      urinary sodium excretion were noted at one year. The mean daily dose of the
      individual components of T+V (2.9 +/- 0.8 mg, T/219 +/- 21.1 mg V) was
      significantly lower than the dose of either T alone 5.5 +/- 1.1 mg/day (P < 0.01)
      or V alone 314.8 +/- 46.3 mg, given in two divided doses (P < 0.01). CONCLUSION:
      These data support the concept that the combination of an ACE inhibitor with a
      non-DHPCA reduce proteinuria to a greater extent than either agent alone. This
      added antiproteinuric effect occurs at lower doses of each drug and is
      independent of further reductions in arterial pressure. These findings could have
      ramifications for slowing renal disease progression in patients with nephropathy
      from type 2 diabetes.

PMID- 9767546
TI  - Autoxidation products of both carbohydrates and lipids are increased in uremic
      plasma: is there oxidative stress in uremia?
AB  - BACKGROUND: Advanced glycation end products (AGEs), formed by non-enzymatic
      glycation and oxidation (glycoxidation) reactions, have been implicated in the
      pathogenesis of several diseases, including normoglycemic uremia. AGE research in
      uremia has focused on the accumulation of carbohydrate-derived adducts generated
      by the Maillard reaction. Recent studies, however, have demonstrated that one
      AGE, the glycoxidation product carboxymethyllysine (CML), could be derived not
      only from carbohydrates but also from oxidation of polyunsaturated fatty acids in
      vitro, raising the possibility that both carbohydrate and lipid autoxidation
      might be increased in uremia. METHODS: To address this hypothesis, we applied gas
      chromatography-mass spectrometry and high performance liquid chromatography to
      measure protein adducts formed in uremic plasma by reactions between carbonyl
      compounds and protein amino groups: pentosidine derived from carbohydrate-derived
      carbonyls, malondialdehyde (MDA)-lysine derived from lipid-derived carbonyls, and
      CML originating possibly from both sources. RESULTS: All three adducts were
      elevated in uremic plasma. Plasma CML levels were mainly (>95%) albumin bound.
      Their levels were not correlated with fructoselysine levels and were similar in
      diabetic and non-diabetic patients on hemodialysis, indicating that their
      increase was not driven by glucose. Pentosidine and MDA-lysine were also
      increased in plasma to the same extent in diabetic and non-diabetic hemodialysis
      patients. Statistical analysis indicated that plasma levels of CML correlated
      weakly (P < 0.05) with those of pentosidine and MDA-lysine, but that pentosidine
      and MDA-lysine varied independently (P > 0.5). CONCLUSIONS: These data suggest
      that the increased levels of AGEs in blood, and probably in tissues, reported in
      uremia implicate a broad derangement in non-enzymatic biochemistry involving
      alterations in autoxidation of both carbohydrates and lipids.

PMID- 9767547
TI  - The multidimensional nature of renal disease: rates and associations of
      albuminuria in an Australian Aboriginal community.
AB  - BACKGROUND: An epidemic of end-stage renal disease (ESRD) is accompanying the
      rising rates of hypertension, type 2 diabetes and cardiovascular disease among
      Aborigines in the Northern Territory of Australia. Incidence rates are now 21
      times those of nonAboriginal Australians and are doubling every four years. We
      describe the rates and associations of renal disease in one remote community,
      which has a current ESRD incidence of 2700 per million, and cardiovascular
      mortality among the highest in Australia. METHODS: Between 1992 and 1995 a
      community-wide screening program was conducted, in which the urinary
      albumin/creatinine ratio (ACR) was used as the chief renal disease marker. More
      than 90% of the population ages five and older participated. RESULTS: Albuminuria
      was evident in early childhood and increased dramatically with age; 26% of adults
      had microalbuminuria and 24% had overt albuminuria. All renal failure developed
      out of a background of overt albuminuria. ACR was significantly correlated with
      the presence of scabies at screening, with a history of poststreptococcal
      glomerulonephritis, which is epidemic and endemic in the community, with
      increasing body wt, blood pressure, glucose, insulin and lipid levels, and with
      evidence of heavy drinking. ACR was also significantly and inversely correlated
      with birth weight. As a result of its association with deteriorating hemodynamic
      and metabolic profiles, increasing ACR was also correlated with increasing
      cardiovascular risk score. Direct observations showed, and multivariate models
      predicted, progressive amplification of ACR when multiple risk factors were
      present simultaneously. Albuminuria also clustered in families. CONCLUSION: Renal
      disease in this population is multifactorial, with risk factors related to whole
      of-life nutrition, metabolic and hemodynamic profiles, infections, health
      behaviors, and possibly a family predisposition. Its relationship to low birth
      weight, and its associations with deteriorating metabolic and hemodynamic
      profiles, suggest that renal disease is, in part, a component of Syndrome X,
      which explains the simultaneous increase in metabolic, cardiovascular and renal
      disease in Aboriginal people. The family clustering might have both environmental
      and genetic causes, and is under further investigation. Most of the identified
      risk factors arise out of poverty, disadvantage and accelerated lifestyle change,
      and the current epidemic can be explained by the confluence of many risk factors
      in the last few decades. The introduction of effective and sustained programs to
      address social, economic and educational inequities in all Aboriginal
      communities, and of screening and renal- and cardiovascular-protective treatment
      programs for those already afflicted are matters of great urgency.

PMID- 9767548
TI  - American Indian heritage and risk factors for renal injury.
AB  - BACKGROUND: Little is known about the causes and consequences of renal disease
      among American Indians in the Great Lakes region of the United States. METHODS:
      We examined clinical correlates of albumin/creatinine ratios among 1368
      participants in the three tribal communities of the Inter-Tribal Heart Project
      using univariate and multivariate analysis. RESULTS: Compared to 1086
      participants without albuminuria, the 240 with microalbuminuria (30 to 299 mg/g)
      and the 42 with macroalbuminuria (>300 mg/g) were more likely to report a history
      of a myocardial infarction (6.4%, 16.0%, and 23.8%, respectively, P < 0.001).
      Similarly, compared to patients without albuminuria, those with microalbuminuria
      and macroalbuminuria were more likely to report a history of stroke (2.3%, 8.4%
      and 26.2%, respectively, P < 0.001). In a multiple linear regression model,
      independent correlates of albumin excretion (P < 0.05) included: fasting blood
      sugar, treated diabetes, treated hypertension, higher systolic blood pressure,
      lower diastolic blood pressure, abnormal electrocardiogram, a history of stroke,
      the degree of American Indian heritage, and lower household income. CONCLUSIONS:
      Urinary albumin excretion is associated with cardiovascular disease outcomes and
      risk factors among American Indians of the Great Lakes region. Both heredity and
      socioeconomic status appear to play a role in the pathogenesis of renal injury in
      this population.

PMID- 9767549
TI  - Effects of ribavirin on hepatitis C-associated nephrotic syndrome in four liver
      transplant recipients.
AB  - BACKGROUND: Hepatitis C virus infection (HCV) is associated with a variety of
      extrahepatic disorders such as membranoproliferative glomerulonephritis (MPGN),
      which is generally due to cryoglobulinemia. After liver transplantation for HCV
      cirrhosis, alpha-interferon treatment against the recurrence of HCV in the liver
      graft is poorly effective and may induce intractable graft rejection. METHODS: We
      describe the cases of four liver transplant recipients treated with ribavirin for
      HCV-related glomerulopathy and nephrotic syndrome. RESULTS: The nephrotic
      syndrome was attenuated or disappeared during ribavirin therapy, and patients
      showed a marked decrease in proteinuria and an increase in albuminemia. The
      syndrome relapsed in two patients when ribavirin therapy was stopped, and a
      favorable response was again obtained in both cases when the treatment was
      resumed. The main adverse effect of ribavirin was anemia in two patients with
      renal impairment. No graft rejection occurred. CONCLUSIONS: These findings
      suggest that continuous therapy with low doses of oral ribavirin may improve the
      proteinuria of hepatitis C-related glomerulonephritis, at least in liver
      transplant recipients.

PMID- 9767550
TI  - Unfavorable course of minimal change nephrotic syndrome in children with
      intrauterine growth retardation.
AB  - BACKGROUND: Intrauterine growth retardation (IUGR) is associated with higher
      morbidity and mortality not only in perinatal life but also in later life. The
      purpose of our study was to determine whether IUGR has any effect on the course
      of minimal change nephrotic syndrome (MCNS) in children. METHODS: Forty children
      who were between 1 and 16 years old at the onset of MCNS, who have been followed
      for at least three years and for whom we were able to obtain birth weights and
      gestational ages, were included. The diagnosis of MCNS was predicted on the basis
      of clinical and laboratory features, and in 11 children (27.5%) the diagnosis was
      confirmed by renal biopsy. IUGR was defined as birth weight below the tenth
      percentile for gestational age. RESULTS: Five children (12.5%) had signs of IUGR
      at birth. In children with IUGR, we observed a higher mean number of relapses
      (10.4 vs. 3.3, P < 0.001) and a higher incidence of steroid dependency (80% vs.
      21%, P < 0.02) than in children without IUGR. Other differences between children
      with and those without IUGR included more frequent treatment with cytotoxic
      agents and cyclosporine, and a higher incidence of renal biopsy in children with
      IUGR. CONCLUSION: Our study demonstrated an unfavorable course of MCNS in
      children with IUGR. IUGR could therefore enable early identification of those
      children who are at risk of becoming frequent relapsers and of developing steroid
      dependency. This, however, should be confirmed in a larger number of patients.

PMID- 9767551
TI  - Activation of both coagulation and fibrinolysis in childhood hemolytic uremic
      syndrome.
AB  - BACKGROUND: Thrombotic microangiopathy is the fundamental lesion in diarrhea
      associated hemolytic uremic syndrome. The extent of the lesion in the renal
      parenchyma determines the severity and outcome of the disorder, bilateral renal
      cortical necrosis being the worst end of the spectrum. In the early years,
      intravascular coagulation was considered the most important pathogenic mechanism.
      Yet, individual coagulation factors were normal in the vast majority of patients
      and therapy with anticoagulants did not alter the course. Recent studies indicate
      that impaired fibrinolysis might be of importance. METHODS: We studied seven
      variables of the coagulation pathway (PT, aPTT, fibrinogen, FVIII:c, von
      Willebrand factor, thrombin-antithrombin complexes, prothrombin fragments 1+2)
      and seven parameters of the fibrinolytic system (plasminogen, alpha2-antiplasmin,
      C1-esterase inhibitor, tissue-type plasminogen activator, urokinase-type
      plasminogen activator, plasminogen activator inhibitor type 1, D-dimer) in 24
      pediatric patients with diarrhea-associated hemolytic uremic syndrome and in 15
      children with acute renal failure not due to hemolytic uremic syndrome. Samples
      were collected at diagnosis and every second day thereafter for a period of ten
      days. Additional samples were collected from patients who underwent dialysis,
      that is, before and after each session from those subjected to hemodialysis and
      every day from those subjected to peritoneal dialysis. The obtained data were
      compared with data from a control group consisting of healthy children. RESULTS:
      Our data show four important features. (1) A significant increase in both
      thrombin-antithrombin complexes (P < 0.005) and prothrombin fragments 1 + 2 (P <
      0.001) is observed in hemolytic uremic patients as compared to patients with
      acute renal failure of other causes. This finding is clearly indicative for an
      activation of the coagulation pathway. (2) Patients with the hemolytic uremic
      syndrome have significantly higher D-dimer levels, a sensitive marker of fibrin
      specific fibrinolysis, as compared to patients with acute renal failure of other
      causes (P < 0.005). (3) Levels of plasminogen activator inhibitor-1 (active
      antigen as well as plasminogen activator inhibitor-1 activity) are not different
      in both patient groups. In contrast, plasma levels of tissue-type plasminogen
      activator and urokinase-type plasminogen activator are significantly higher in
      the hemolytic uremic patients than in those with acute renal failure of other
      causes (P < 0.01 and P < 0.05 respectively). (4) Hemodialysis leads to an
      increase in tissue-type plasminogen activator antigen and a decrease of
      plasminogen activator inhibitor-1 activity levels. CONCLUSIONS: Our data
      demonstrate that in children with diarrhea-associated hemolytic uremic syndrome,
      limited intravascular coagulation occurs, without evidence of impaired
      fibrinolysis.

PMID- 9767553
TI  - Role of cytokines in the response to erythropoietin in hemodialysis patients.
AB  - BACKGROUND: Cytokines are regulatory factors of erythropoiesis, especially in
      pathologic conditions. Even though a relevant role for a deranged cytokine
      production in the pathogenesis of dialysis anemia has been suggested, no data are
      available that analyze the role of cytokines in the key therapeutic issue of the
      needs of erythropoietin. The aim of the present study in hemodialysis patients
      was, therefore, to examine the relationship between the dose of recombinant human
      erythropoietin (EPO) and the production of cytokines by peripheral blood
      mononuclear cells (PBMC). METHODS: After the exclusion of subjects with major
      active causes of EPO resistance, data from 34 hemodialysis patients were
      available for analysis. Cytokine levels were measured in the supernatants of
      stimulated [with bacterial lipopolysaccharide and interferon gamma (IFN-gamma)]
      and unstimulated PBMC. Mean yearly values of hematocrit, hemoglobin, transferrin
      saturation, ferritin, parathormone (PTH) and aluminum levels and EPO doses
      (U/kg/week) were calculated. For analysis, the 34 patients were divided according
      to their cutoff requirements for EPO: patients with requirements of EPO > or = 60
      U/kg/week (group A1, 26 subjects) versus EPO < 60 U/kg/week (group B1, 8
      subjects) and patients with requirements of EPO > or = 100 U/kg/week (group A2,
      18 subjects) versus <100 U/kg/week (group B2, 16 subjects). RESULTS: A
      significant direct correlation between interleukin-6 (IL-6) and tumor necrosis
      factor alpha (TNF-a) production values and EPO doses was found (P = 0.039 and P =
      0.02 respectively). On the other hand, there was a significantly negative
      correlation between interleukin-12 (IL-12) production values and EPO doses (P =
      0.029). Patients of groups A1 and A2 had spontaneously higher tumor necrosis
      factor-alpha (TNF-alpha) and lower IL-12 and IFNgamma production compared to
      patients from groups B1 and B2. CONCLUSIONS: Our data disclose a previously
      undescribed pattern of cytokine alteration that is relevant to determine
      increased needs of EPO in hemodialysis patients. The present results have
      potential applicability in designing strategies to improve EPO resistance.

PMID- 9767552
TI  - Detection of urinary tract infections by reduction of nitroblue tetrazolium.
AB  - BACKGROUND: Nitroblue tetrazolium (NBT) reduction to formazan has been used as a
      marker for nitric oxide synthase (NOS). Since inducible NOS activity is elevated
      in urine from patients with urinary tract infections (UTIs), we investigated the
      accuracy of NBT reduction as an early predictor of UTIs and quantified the
      relationship between inducible NOS and NBT. METHODS: Urine samples from 434
      patients were screened for the presence of UTIs with leukocyte-esterase and
      nitrite dipsticks and with NBT reduction. The rapid screening results from each
      test were compared to urine culture results. In addition, NBT reduction
      parameters were measured in urine pellet at 595 nm after incubation with one of
      four factors: NOS cofactors, NOS inhibitors, NADH, or superoxide
      dismutase/catalase. RESULTS: As a urine screening test for UTIs, NBT reduction
      was more sensitive with a higher negative predictive accuracy than the nitrite
      dipstick. NBT reduction also was more specific with a higher positive predictive
      accuracy and negative predictive accuracy than the leukocyte-esterase dipstick.
      In infected urine pellet, both NADPH, a NOS cofactor, and NADH increased NBT
      reduction. Superoxide dismutase/catalase decreased NBT reduction. CONCLUSIONS:
      Although NOS may not be the only NBT reducing enzyme, rapid, visible reduction of
      NBT is induced in urine from patients with UTIs.

PMID- 9767554
TI  - Effects of estrogen replacement therapy on the lipoprotein profile in
      postmenopausal women with ESRD.
AB  - BACKGROUND: Patients with ESRD have excessive cardiovascular morbidity and
      mortality. In postmenopausal women with normal renal function, estrogen
      replacement therapy decreases cardiovascular mortality by 50%, in part because of
      their beneficial effects on the lipoprotein profile. Because of similarities in
      the lipoprotein profile between healthy, postmenopausal women, and women with
      ESRD, we examined the effects of estrogen replacement on lipoproteins in 11
      postmenopausal women with ESRD. METHODS: In a randomized, placebo-controlled
      crossover study (8 week treatment arms) using 2 mg daily of oral, micronized
      estradiol, 11 postmenopausal women with ESRD were treated. Neither baseline lipid
      nor lipoprotein abnormalities were used as entry criteria for study
      participation. RESULTS: Blood estradiol levels were 19 +/- 4 with placebo and 194
      +/- 67 pg/ml (P = 0.024) with estradiol treatment. Total HDL cholesterol
      concentrations increased from 52 +/- 19 mg/dl to 61 +/- 20 mg/dl (16%), with
      placebo and estradiol treatments, respectively (P = 0.002). Apolipoprotein A1
      increased by 24.6% (P = 0.0002) with estradiol intervention. HDL2 concentrations
      were 19 +/- 13 with placebo and 24 +/- 16 with estradiol treatment (P = 0.046).
      There were no differences in total or LDL cholesterol, other lipoprotein
      fractions including Lp(a), and triglycerides with 2 mg daily estradiol treatment.
      No significant side effects were observed. CONCLUSIONS: Therefore, using standard
      dosage regimens for estrogen replacement therapy in postmenopausal women with
      ESRD, HDL cholesterol is increased to an extent that would be expected to improve
      their cardiovascular risk profile. Further studies are needed to assess whether
      estrogen replacement therapy decreases the incidence or severity of
      cardiovascular disease in ESRD patients to a similar degree compared with other
      women.

PMID- 9767555
TI  - Randomized comparison of triple therapy and antithymocyte globulin induction
      treatment after simultaneous pancreas-kidney transplantation.
AB  - BACKGROUND: The incidence of acute rejection is considered to be higher after
      simultaneous pancreas-kidney (SPK) transplantation as compared to renal
      transplant alone. Therefore, the majority of SPK transplant recipients commonly
      receive a combination of cyclosporine (CsA) or tracolimus, and azathioprine or
      mycophenolic mofetyl, corticosteroids and/or antilymphocyte preparations. This
      study was designed to compare two immunosuppressive protocols for the prevention
      of acute rejection in patients undergoing SPK transplantation. The primary end
      point was the incidence of acute rejection during the first 12 months after
      transplantation METHODS: Fifty patients with type-I insulin-dependent diabetes
      and chronic renal failure were randomized to receive a triple drug
      immunosuppressive regimen including CsA, azathioprine and corticosteroids (N =
      25), or the quadruple sequential combination of rabbit antithymocyte globulin
      (ATG) given for 10 days, azathioprine, corticosteroids and delayed CsA (N = 25).
      Maintenance immunosuppression (CsA and azathioprine, without corticosteroids) was
      similar in both arms. RESULTS: The average follow-up was 36 months in both groups
      (range 9 to 60 months). No patient was excluded from the study. Although the
      percentage of patients with adverse events was higher in the ATG group (80 vs.
      40%, P < 0.01), none of them resulted in premature discontinuation of the drug.
      Patients receiving ATG experienced a lower incidence (36% vs. 76%, P < 0.01) and
      number (13 vs. 29, P < 0.05) of acute renal rejection episodes. However, no
      difference was observed in patient, pancreas and kidney survival rates between
      groups. No case of isolated pancreas rejection was observed. CONCLUSIONS: The
      quadruple sequential combination ATG, azathioprine, corticosteroid and CsA
      significantly reduced the one year incidence of acute renal rejection after SPK
      transplantation, compared to a triple immunosuppressive regimen.

PMID- 9767556
TI  - N epsilon-(carboxymethyl)lysine in blood from maintenance hemodialysis patients
      may contribute to dialysis-related amyloidosis.
AB  - BACKGROUND: Recent studies demonstrated not only that advanced glycation end
      product could be found in amyloid tissue from patient with dialysis related
      amyloidosis, but also that amyloid beta2-microglobulin was modified with
      N(epsilon)-(carboxymethyl)lysine (CML). We wanted to determine if CML could be a
      biomarker in these patients. METHODS: To raise polyclonal anti
      carboxymethyllysine antibody, human serum albumin was carboxymethylated by
      glyoxylic acid and was immunized to rabbits as antigen. Carboxymethyllysine
      hemoglobin (CML-Hb) levels were measured by the dot blotting method using this
      antibody. RESULTS: The levels of CML-Hb were 6.68 +/- 3.10 nmol CML/mg Hb in
      nondiabetic hemodialysis patients (N = 70), 6.39 +/- 3.43 nmol CML/mg Hb in
      diabetic hemodialysis patient (N = 21), and 3.13 +/- 0.88 nmol CML/mg Hb in 47
      healthy volunteers. For clinical signs of dialysis-related amyloidosis, 70
      nondiabetic hemodialysis patients were scored according Gejyo's criteria. The CML
      Hb levels in patients with a high amyloid score as well as a low amyloid score
      were significantly higher than in patients with negative amyloid score (8.89 +/-
      3.53 nmol CMLmg Hb, 7.28 +/- 2.32 nmol CML/mg Hb vs. 5.11 +/- 2.09 nmol CML/mg
      Hb, P < 0.001, P < 0.05). Furthermore, the CML-Hb levels correlated significantly
      with serum values of the methylguanidine over creatinine ratio and hyaluronate.
      CONCLUSIONS: We suggest that CML-Hb is increased in blood from patients on
      maintenance hemodialysis and is thus a potential biomarker of oxidative damage in
      these patients. Moreover, CML-modification of protein may play a pathogenic role
      in the development of dialysis related amyloidosis.

PMID- 9767557
TI  - Outbreak of sterile peritonitis among continuous cycling peritoneal dialysis
      patients.
AB  - BACKGROUND: Approximately 30,000 patients receive peritoneal dialysis in the
      United States. In August 1996, several dialysis centers from different states
      reported sterile peritonitis among CCPD patients using sterile peritoneal
      dialysis solution (PDS) from a single manufacturer. The manufacturer recalled 53
      lots of PDS that had passed established industry guidelines and Food and Drug
      Administration (FDA) approved quality control tests [including endotoxin levels
      <0.5 endotoxin units (EU)/ml], but had pre-sterilization bacterial colony counts
      >1 cfu/ml. METHODS: At one outpatient dialysis center, Hospital of the University
      of Pennsylvania (HUP), we conducted a retrospective cohort study of all CCPD
      patients treated during July 15 to August 30, 1996. A case-patient was defined as
      any HUP patient with culture-negative peritoneal fluid with a white blood cell
      count >100/mm3, cloudy peritoneal fluid, and/or abdominal pain. PDS and tubing
      were cultured for bacteria and assayed for endotoxin. RESULTS: Overall, 14 of 28
      patients had sterile peritonitis. The only risk factor identified was exposure to
      > or =1 lot of recalled PDS (14 of 22 vs. 0/6, P = 0.02); the more recalled lots
      received, the higher the attack rate (P = 0.0001). Five of 47 PDS bags had
      detectable endotoxin; recalled lots were more likely to have measurable endotoxin
      than nonrecalled lots (5/19 vs. 0/17, P = 0.05). When case-patients resumed CCPD
      using PDS from non-recalled lots, no further cases were reported. CONCLUSIONS:
      Our results suggest that this outbreak was caused by intrinsic PDS contamination
      with endotoxin. Pre-sterilization colony counts may be an important quality
      control indicator for CCPD fluids in conjunction with endotoxin levels.

PMID- 9767558
TI  - Estimation of peritoneal mass transport by three-pore model in children.
AB  - BACKGROUND: Computerized modeling is increasingly used to optimize the efficacy
      of peritoneal dialysis (PD). The Personal Dialysis Capacity (PDC) test is a new
      tool to model PD efficacy based on the three-pore model of peritoneal mass
      transport. We sought to evaluate (i) whether the PDC test is applicable to
      children on chronic PD, and (ii) whether the physiological mass transport
      coefficients defined in the three pore model are dependent on age or body size in
      childhood. METHODS: A validation study was performed in 32 pediatric chronic PD
      patients. Twenty tests were performed using a standard CAPD regimen, and 22 tests
      using a simplified automated PD (APD) protocol. Test accuracy and precision were
      evaluated by comparison of predicted with measured 24-hour dialysate clearances
      of urea, creatinine, beta2-microglobulin and albumin and ultrafiltration rates.
      Long-term reproducibility was assessed in 16 patients by repeated clearance
      studies after a median time interval of 10 weeks. RESULTS: While daily clearances
      of urea and creatinine were predicted with good precision and accuracy with both
      test protocols (concordance correlation coefficients 0.90 to 0.98, mean
      difference predicted-calculated -0.6 to +0.6 ml/min/1.73 m2), ultrafiltration
      rates were predicted more closely by the APD (r = 0.97) than by the CAPD test
      (0.80). Middle and large molecule clearances were predicted less precisely in
      both test settings (r = 0.48 to 0.83). Re-test reproducibility was slightly lower
      than the predictive precision observed in the original test (r = 0.80 to 0.91).
      The calculated total peritoneal pore area increased in absolute terms, decreased
      with body size when standardized to weight, and was independent of body size when
      normalized to body surface area. The body size-normalized fluid reabsorption rate
      was slightly increased in young infants compared to older children or adults.
      CONCLUSIONS: The PDC test permits to model peritoneal solute and water transport
      with remarkable precision in children of all age groups. While the peritoneal
      pore area is a linear function of body surface area, fluid reabsorption appears
      to be slightly increased in young infants.

PMID- 9767559
TI  - Serum total homocysteine concentration before and after renal transplantation.
AB  - BACKGROUND: Hyperhomocysteinemia is by now an established risk factor for the
      development of atherosclerosis. Total homocysteine concentration (tHcy)
      correlates inversely with glomerular filtration rate, and it is roughly three
      times as high in hemodialysis patients as in healthy individuals. Therefore, tHcy
      would be expected to fall markedly after successful renal transplantation. The
      aim of the present study was to assess the changes in tHcy associated with renal
      transplantation. METHODS: tHcy was analyzed in samples collected before renal
      transplantation and at six months after transplantation in 55 stable patients,
      all of whom were treated with cyclosporine (CS). tHcy was also analyzed in
      samples from 55 controls characterized by markers of renal function that matched
      those of the post-transplant state. RESULTS: At six months after transplantation,
      tHcy was significantly decreased as compared with pretransplant tHcy (27.7 +/-
      14.8 vs. 36.9 +/- 21.3 micromol/liter, P < 0.001). Post-transplant tHcy was
      markedly higher than the tHcy of the control group (27.7 +/- 14.8 vs. 16.0 +/-
      5.3 micromol/liter, P < 0.0001). The post-transplant change in tHcy ranged
      widely, the average change being a reduction of 14%. Sixteen patients (29%)
      actually manifested an increase in post-transplant tHcy. The post-transplant
      changes in tHcy correlated inversely with pretransplant tHcy (r = -0.66, P <
      0.0001) and directly with the changes in serum albumin concentrations (r = 0.35,
      P < 0.05) and CS trough concentrations (r = 0.29, P < 0.05). A multivariate
      analysis, including the post-transplant changes in serum concentrations of folate
      and albumin as well as creatinine clearances explained 21% of the change in tHcy
      (P < 0.05). After inclusion of the CS concentration, an independent predictor,
      the model accounted for 28% of the post-transplant change in tHcy (P < 0.01).
      CONCLUSION: The post-transplant reduction in tHcy was far smaller than expected
      with respect to renal function, and the post-transplant changes in the major
      biochemical determinants of tHcy contributed relatively little to explain the
      change in tHcy. Thus, the results suggest the post-transplant introduction of one
      or more factors that induce an increase in tHcy. Treatment with CS appears to be
      such a factor.

PMID- 9767560
TI  - Influence of hematocrit on the measurement of lipoproteins demonstrated by the
      example of lipoprotein(a).
AB  - BACKGROUND: The measurement of many parameters of human blood is usually
      performed in plasma or serum. Since lipoproteins or apolipoproteins, for example,
      are found almost exclusively in the plasma fraction after low-speed
      centrifugation, these parameters can be expected to be distributed in a different
      plasma volume depending on the hematocrit value. Therefore, the measured plasma
      levels might be relatively too low or too high in comparison to the whole blood
      concentrations in the case of abnormal hematocrit levels. The aim of our
      experiments was to evaluate the extent of differences between whole blood and
      plasma concentrations, taking as an example lipoprotein(a) [Lp(a)] in
      hemodialysis patients with documented decreased hematocrit values. METHODS: Lp(a)
      was measured in plasma as well as whole blood of 15 hemodialysis patients with
      low hematocrit values (0.29 +/- 0.02) in comparison to 11 control subjects (0.45
      +/- 0.04). RESULTS: Plasma concentrations were 27% higher in patients than in
      controls (19.7 vs. 15.5 mg/dl). The relative difference was twice as high (59%)
      when measured in whole blood (13.5 vs. 8.5 mg/dl). Similar relative differences
      were observed when whole blood concentrations of 125 hemodialysis patients and
      256 controls were calculated with the formula [Lp(a)plasma * (1-hematocrit)].
      CONCLUSIONS: Our findings clearly demonstrate that hematocrit is a strong
      confounding variable of lipoprotein measurement in epidemiological studies when
      concentrations are measured in plasma, especially in cases of abnormal hematocrit
      values. Furthermore, studies investigating the longitudinal changes of
      lipoproteins should consider potential hematocrit changes.

PMID- 9767561
TI  - Molecular pathogenesis of Bartter's and Gitelman's syndromes.

PMID- 9767562
TI  - FadR, transcriptional co-ordination of metabolic expediency.
AB  - FadR is an Escherichia coli transcriptional regulator that optimizes fatty acid
      metabolism in response to exogenously added fatty acids. Many bacteria grow well
      on long-chain fatty acids as sole carbon source, but at the expense of consuming
      a useful structural material. Exogenous fatty acids are readily incorporated into
      membrane phospholipids in place of the acyl chains synthesized by the organism,
      and phospholipids composed of any of a large variety of exogenously derived acyl
      chains make biologically functional membranes. It would be wasteful for bacteria
      to degrade fatty acids to acetyl-CoA and then use this acetyl-CoA to synthesize
      the same (or functionally equivalent) fatty acids for phospholipid synthesis.
      This line of reasoning suggests that bacteria might shut down endogenous fatty
      acid synthesis on the addition of long-chain fatty acids to the growth medium.
      Moreover, this shutdown could be closely coupled to fatty acid degradation, such
      that a bacterial cell would use a portion of the exogenous fatty acid for
      phospholipid synthesis while degrading the remainder to acetyl-CoA. To a degree,
      the bacterium could both have its cake (the acyl chains for phospholipid
      synthesis) and eat it (to form acetyl-CoA). This scenario turns out to be true in
      E. coli. The key player in this regulatory gambit is FadR, a transcription factor
      that acts both as a repressor of the fatty acid degradation and as an activator
      of fatty acid biosynthesis.

PMID- 9767563
TI  - A glycyl radical solution: oxygen-dependent interconversion of pyruvate formate
      lyase.
AB  - Pyruvate formate-lyase (PFL) catalyses the non-oxidative dissimilation of
      pyruvate to formate and acetyl-CoA using a radical-chemical mechanism. The enzyme
      is enzymically interconverted between inactive and active forms, the active form
      contains an organic free radical located on a glycyl residue in the C-terminal
      portion of the polypeptide chain. Introduction of the radical into PFL only
      occurs anaerobically, and the activating enzyme responsible is an iron-sulphur
      protein that uses S-adenosyl methionine as cofactor and reduced flavodoxin as
      reductant. As the radical form of PFL is inactivated by molecular oxygen it is
      safeguarded during the transition to aerobiosis by conversion back to the radical
      free, oxygen-stable form. This reaction is catalysed by the anaerobically induced
      multimeric enzyme alcohol dehydrogenase. The genes encoding PFL and its
      activating enzyme are adjacent on the chromosome but form discrete
      transcriptional units. This genetic organization is highly conserved in many, but
      not all, organisms that have PFL. Recent studies have shown that proteins
      exhibiting significant similarity to PFL and its activating enzyme are relatively
      widespread in facultative and obligate anaerobic eubacteria, as well as archaea.
      The physiological function of many of these PFL-like enzymes remains to be
      established. It is becoming increasingly apparent that glycyl radical enzymes are
      more prevalent than previously surmised. They represent a class of enzymes with
      unusual biochemistry and probably predate the appearance of molecular oxygen.

PMID- 9767564
TI  - Archaea and the cell cycle.
AB  - Sequence similarity data suggest that archaeal chromosome replication is
      eukaryotic in character. Putative nucleoid-processing proteins display
      similarities to both eukaryotic and bacterial counterparts, whereas cell division
      may occur through a predominantly bacterial mechanism. Insights into the
      organization of the archaeal cell cycle are therefore of interest, not only for
      understanding archaeal biology, but also for investigating how components from
      the other two domains interact and work in concert within the same cell; in
      addition, archaea may have the potential to provide insights into eukaryotic
      initiation of chromosome replication.

PMID- 9767565
TI  - Morphological adaptation and inhibition of cell division during stationary phase
      in Caulobacter crescentus.
AB  - During exponential growth, each cell cycle of the alpha-purple bacterium
      Caulobacter crescentus gives rise to two different cell types: a motile swarmer
      cell and a sessile stalked cell. When cultures of C. crescentus are grown for
      extended periods in complex (PYE) medium, cells undergo dramatic morphological
      changes and display increased resistance to stress. After cultures enter
      stationary phase, most cells are arrested at the predivisional stage. For the
      first 6-8 days after inoculation, the colony-forming units (cfu) steadily
      decrease from 10(9) cfu ml(-1) to a minimum of 3x10(7) cfu ml(-1) after which
      cells gradually adopt an elongated helical morphology. For days 9-12, the cfu of
      the culture increase and stabilize around 2 x 10(8) cfu ml(-1). The viable cells
      have an elongated helical morphology with no constrictions and an average length
      of 20 microm, which is 15-20 times longer than exponentially growing cells. The
      level of the cell division initiation protein FtsZ decreases during the first
      week in stationary phase and remains at a low constant level consistent with the
      lack of cell division. When resuspended in fresh medium, the elongated cells
      return to normal size and morphology within 12 h. Cells that have returned from
      stationary phase proceed through the same developmental changes when they are
      again grown for an extended period and have not acquired a heritable growth
      advantage in stationary phase (GASP) compared with overnight cultures. We
      conclude that the changes observed in prolonged cultures are the result of entry
      into a new developmental pathway and are not due to mutation.

PMID- 9767566
TI  - Identification of a novel gene involved in pilin glycosylation in Neisseria
      meningitidis.
AB  - The pili of Neisseria meningitidis are a key virulence factor, being major
      adhesins of this capsulate organism that contribute to specificity for the human
      host. Recently it has been reported that meningococcal pili are post
      translationally modified by the addition of an O-linked trisaccharide, Gal (beta1
      4) Gal (alpha1-3) 2,4-diacetimido-2,4,6-trideoxyhexose. Using a set of random
      genomic sequences from N. meningitidis strain MC58, we have identified a novel
      gene homologous to a family of glycosyltransferases. A plasmid clone containing
      the gene was isolated from a genomic library of N. meningitidis strain MC58 and
      its nucleotide sequence determined. The clone contained a complete copy of the
      gene, here designated pglA (pilin glycosylation). Insertional mutations were
      constructed in pglA in a range of meningococcal strains with well-defined
      lipopolysaccharide (LPS) or pilin-linked glycan structures to determine whether
      pglA had a role in the biosynthesis of these molecules. There was no alteration
      in the phenotype of LPS from pglA mutant strains as judged by gel migration and
      the binding of monoclonal antibodies. In contrast, decreased gel migration of the
      pilin subunit molecules of pglA mutants was observed, which was similar to the
      migration of pilins of galE mutants of same strains, supporting the notion that
      pglA is a glycosyltransferase involved in the biosynthesis of the pilin-linked
      trisaccharide structure. The pglA mutation, like the galE mutation reported
      previously, had no effect on pilus-mediated adhesion to human epithelial or
      endothelial cells. Pilin from pglA mutants were unable to bind to monospecific
      antisera recognizing the Gal (beta1-4) Gal structure, suggesting that PglA is a
      glycosyltransferase involved in the addition of galactose of the trisaccharide
      substituent of pilin.

PMID- 9767567
TI  - Regulation of Pseudomonas aeruginosa hemF and hemN by the dual action of the
      redox response regulators Anr and Dnr.
AB  - The oxidative decarboxylation of coproporphyrinogen III catalysed by an oxygen
      dependent oxidase (HemF) and an oxygen-independent dehydrogenase (HemN) is one of
      the key regulatory points of haem biosynthesis in Pseudomonas aeruginosa. To
      investigate the oxygen-dependent regulation of hemF and hemN, the corresponding
      genes were cloned from the P. aeruginosa chromosome. Recognition sequences for
      the Fnr-type transcriptional regulator Anr were detected -44.5 bp from the 5' end
      of the hemF mRNA transcript and at an optimal distance of -41.5 bp with respect
      to the transcriptional start of hemN. An approximately 10-fold anaerobic
      induction of hemN gene expression was mediated by the dual action of Anr and a
      second Fnr-type regulator, Dnr. Regulation by both proteins required the Anr
      recognition sequence. Surprisingly, aerobic expression of hemN was dependent only
      on Anr. An anr mutant did not contain detectable amounts of hemN mRNA and
      accumulated coproporphyrin III both aerobically and anaerobically, indicating the
      importance of HemN for aerobic and anaerobic haem formation. Mutation of hemN and
      hemF did not abolish aerobic or anaerobic growth, indicating the existence of an
      additional HemN-type enzyme, which was termed HemZ. Expression of hemF was
      induced approximately 20-fold during anaerobic growth and, as was found for hemN,
      both Anr and Dnr were required for anaerobic induction. Paradoxically, oxygen is
      necessary for HemF catalysis, suggesting the existence of an additional
      physiological function for the P. aeruginosa HemF protein.

PMID- 9767568
TI  - Site-directed mutagenesis and virulence assessment of the katG gene of
      Mycobacterium intracellulare.
AB  - Mycobacterial catalases have been suggested as acting as virulence factors by
      protecting intracellular mycobacteria from reactive oxidative metabolites
      produced by host phagocytes. Mycobacterium intracellulare, like many other
      mycobacteria, produces two proteins with catalase activity: a heat-stable
      catalase (KatE) and an inducible, heat-labile catalase peroxidase (KatG). The M.
      intracellulare katG gene was cloned, and a plasmid derivative with a 4 bp
      insertion in the katG coding sequence was constructed and used for site-directed
      mutagenesis of M. intracellulare 1403 (ATCC 35761). The resulting katG mutant was
      highly resistant to isoniazid (INH), showed an increased sensitivity to H2O2 and
      had lost peroxidase and heat-sensitive catalase activity but retained heat-stable
      catalase activity. The plasmid carrying the katG frameshift allele was also used
      for mutagenesis of the mouse virulent M. intracellulare isolate D673. After
      intravenous injection into BALB/c mice, D673 and the isogenic katG mutant showed
      the same growth kinetics in the spleen, liver and lungs of the infected mice. Our
      results demonstrate that the KatG catalase peroxidase mediates resistance to H2O2
      and susceptibility to INH but is not an essential virulence factor for the
      survival and growth of M. intracellulare in the mouse.

PMID- 9767569
TI  - botR/A is a positive regulator of botulinum neurotoxin and associated non-toxin
      protein genes in Clostridium botulinum A.
AB  - The genes of the botulinum neurotoxin A (BoNT) complex are clustered in a locus
      consisting of two divergent polycistronic operons, one containing the non-toxic,
      non-haemagglutinin (NTNH) component and bontA genes, the other containing the
      haemagglutinin (HA) component genes. The two operons are separated by a gene
      (botR/A, previously called orf21) encoding a 21 kDa protein. A recombinant
      Clostridium botulinum A strain that overexpresses botR/A was constructed by
      electroporating strain 62 with the vector pAT19 containing botR/A under the
      control of its own promoter. The transformed strain produced more BoNT/A and
      associated non-toxic proteins (ANTPs) and the corresponding mRNAs than the non
      transformed strain. Partial inhibition of botR/A by antisense mRNA resulted in
      lower levels of BoNT/A, NTNH and HA70 and the levels of the corresponding mRNAs.
      Gel mobility shift assays and immunoprecipitations showed that BotR/A bound to
      the DNA promoter region upstream from the two BoNT/A complex operons. These
      results show that botR/A activated transcription of the genes encoding BoNT/A and
      ANTPs in C. botulinum A by interacting directly with the region promoter, and
      that the homologous genes in C. botulinum B, C and D presumably have the same
      function.

PMID- 9767570
TI  - Probing the active site of mitogillin, a fungal ribotoxin.
AB  - Fungal ribotoxins, such as mitogillin and the related Aspergillus toxins
      restrictocin and alpha-sarcin, are highly specific ribonucleases, which
      inactivate the ribosome enzymatically by cleaving the eukaryotic 28S RNA of the
      large ribosomal subunit at a single phosphodiester bond. The site of cleavage
      occurs between G4325 and A4326, which are present in a 14-base sequence (the
      alpha-sarcin loop) conserved among the large subunit rRNAs of all living species.
      The amino acid residues involved in the cytotoxic activities of mitogillin were
      investigated by introducing point mutations using hydroxylamine into a
      recombinant Met-mature mitogillin (mitogillin with a Met codon at the N-terminus
      and no leader sequence) gene constructed from an Aspergillus fumigatus cDNA
      clone. These constructs were cloned into a yeast expression vector under the
      control of the GAL1 promoter and transformed into Saccharomyces cerevisiae. Upon
      induction of mitogillin expression, surviving transformants revealed that
      substitutions of certain amino acid residues on mitogillin abolished its
      cytotoxicity. Non-toxic mutant genes were cloned into an Escherichia coli
      expression vector, the proteins overexpressed and purified to homogeneity and
      their activities examined by in vitro ribonucleolytic assays. These studies
      identified the His-49Tyr, Glu-95Lys, Arg-120Lys and His-136Tyr mutations to have
      a profound impact on the ribonucleolytic activities of mitogillin. We conclude
      that these residues are key components of the active site contributing to the
      catalytic activities of mitogillin.

PMID- 9767571
TI  - Sequence and analysis of the 60 kb conjugative, bacteriocin-producing plasmid
      pMRC01 from Lactococcus lactis DPC3147.
AB  - The complete sequence of pMRC01, a large conjugative plasmid from Lactococcus
      lactis ssp. lactis DPC3147, has been determined. Using a shotgun sequencing
      approach, the 60,232 bp plasmid sequence was obtained by the assembly of 1056
      underlying sequences (sevenfold average redundancy). Sixty-four open reading
      frames (ORFs) were identified. Analysis of the gene organization of pMRC01
      suggests that the plasmid can be divided into three functional domains, with each
      approximately 20 kb region separated by insertion sequence (IS) elements. The
      three regions are (i) the conjugative transfer region, including a 16-gene Tra
      (transfer) operon; (ii) the bacteriocin production region, including an operon
      responsible for the synthesis of the novel bacteriocin lacticin 3147; and (iii)
      the phage resistance and plasmid replication region of the plasmid. The complete
      sequence of pMRC01 provides important information about these industrially
      relevant phenotypes and gives insight into the structure, function and evolution
      of large gram-positive conjugative plasmids in general. The completely sequenced
      pMRC01 plasmid should also provide a useful framework for the design of novel
      plasmids to be incorporated into starter strain improvement programmes for the
      dairy industry.

PMID- 9767572
TI  - Negative regulation by RpoS: a case of sigma factor competition.
AB  - A mutation in the Escherichia coli gene encoding the stationary phase-inducible
      sigma factor (sigmaS, RpoS) not only abolishes transcription of some genes in
      stationary phase, but also causes superinduction of other stationary phase
      induced genes. We have examined this phenomenon of repression by sigmaS using as
      a model system the divergently transcribed stationary phase-inducible genes, uspA
      and uspB. uspA is transcribed by sigma70-programmed RNA polymerase and is
      superinduced in an rpoS mutant, while uspB induction is sigmaS dependent. The
      data suggest that the superinduction of uspA is caused by an increased amount of
      sigma70 bound to RNA polymerase in the absence of the competing sigmaS.
      Increasing the ability of sigma70 to compete against sigmaS by overproducing
      sigma70 mimics the effect of an rpoS mutation by causing superinduction of
      sigma70-dependent stationary phase-inducible genes (uspA and fadD), silencing of
      sigmaS-dependent genes (uspB, bolAp1 and fadL) and inhibiting the development of
      sigmaS-dependent phenotypes, such as hydrogen peroxide resistance in stationary
      phase. In addition, overproduction of sigmaS markedly reduced stationary phase
      expression of a sigma70-dependent promoter. Thus, we conclude that sigma factors
      compete for a limiting amount of RNA polymerase during stationary phase. The
      implications of this competition in the passive control of promoter activity is
      discussed.

PMID- 9767573
TI  - Expression of ptsG, the gene for the major glucose PTS transporter in Escherichia
      coli, is repressed by Mlc and induced by growth on glucose.
AB  - The gene for the glucose-specific transporter of the phosphotransferase system,
      ptsG, is expressed from two promoters separated by 141 bp. The expression of the
      major, shorter transcript is very strongly dependent upon cAMP/CAP. However,
      unlike other CAP-activated genes, the expression of ptsG is higher in glucose
      media than in glycerol, implying that ptsG is controlled by a glucose-inducible
      regulator. A mutation in the mlc gene greatly enhances ptsG expression in a
      glycerol-grown culture but has no effect on ptsG expression during growth on
      glucose. The mlc gene encodes a transcriptional regulator that has been shown to
      affect the expression of manXYZ and malT. ptsG mRNA levels are lower in the mlc
      strain grown on glucose than in the same strain grown on glycerol. This is
      presumably because of the greater catabolite repression in the glucose culture
      than in glycerol. The final level of expression of ptsG in a mlc+ strain in
      glucose is a compromise between specific induction by glucose and generalized
      catabolite repression. The result is that ptsG expression is very similar in
      glucose-grown cultures of wild-type and mlc strains. The Mlc protein binds to two
      sites centred at -6 and -175 upstream of the major ptsG transcript. CAP binds at 
      40.5 compared with this site, typical of class II CAP-regulated promoters, and
      the binding of CAP and Mlc is co-operative.

PMID- 9767574
TI  - The Escherichia coli relBE genes belong to a new toxin-antitoxin gene family.
AB  - Toxin-antitoxin systems are defined as a group of plasmid- and chromosome-encoded
      loci that specify a cell toxin and a protein antitoxin. Plasmid-encoded toxin
      antitoxin systems stabilize their replicons by killing plasmid-free cells. Here,
      we show that the relBE genes of Escherichia coli K-12 have all the basic features
      previously connected with toxin-antitoxin systems: (i) relE encodes a cytotoxin
      lethal or inhibitory to host cells; (ii) relB encodes an antitoxin that prevents
      the lethal action of the relE-encoded toxin; (iii) the relBE genes stabilize a
      mini-R1 test plasmid; and (iv) the RelB antitoxin autoregulates the relBEF operon
      at the level of transcription. Using database searching, we found relBE
      homologues on the chromosomes of E. coli K-12, Haemophilus influenzae and Vibrio
      cholerae. A fifth relBE homologue was identified on the enterotoxin encoding E.
      coli plasmid P307. Indirect evidence suggests that the toxicity of RelE may be
      related to the inhibition of protein synthesis. Based on these observations, we
      propose a model that explains the delayed relaxed phenotype associated with
      mutations in relB.

PMID- 9767575
TI  - The Escherichia coli threonyl-tRNA synthetase gene contains a split ribosomal
      binding site interrupted by a hairpin structure that is essential for
      autoregulation.
AB  - The expression of the gene encoding Escherichia coli threonyl-tRNA synthetase
      (ThrRS) is negatively autoregulated at the translational level. ThrRS binds to
      its own mRNA leader, which consists of four structural and functional domains:
      the Shine-Dalgarno (SD) sequence and the initiation codon region (domain 1); two
      upstream hairpins (domains 2 and 4) connected by a single-stranded region (domain
      3). Using a combination of in vivo and in vitro approaches, we show here that the
      ribosome binds to thrS mRNA at two non-contiguous sites: region -12 to +16
      comprising the SD sequence and the AUG codon and, unexpectedly, an upstream
      single-stranded sequence in domain 3. These two regions are brought into close
      proximity by a 38-nucleotide-long hairpin structure (domain 2). This domain,
      although adjacent to the 5' edge of the SD sequence, does not inhibit ribosome
      binding as long as the single-stranded region of domain 3 is present. A stretch
      of unpaired nucleotides in domain 3, but not a specific sequence, is required for
      efficient translation. As the repressor and the ribosome bind to interspersed
      domains, the competition between ThrRS and ribosome for thrS mRNA binding can be
      explained by steric hindrance.

PMID- 9767576
TI  - Transcription of rpoH, encoding the Escherichia coli heat-shock regulator
      sigma32, is negatively controlled by the cAMP-CRP/CytR nucleoprotein complex.
AB  - In Escherichia coli, the rpoH gene encoding the essential heat-shock regulator
      sigma32, is expressed in a complex manner. Transcription occurs from four
      promoters (P1, P3, P4 and P5) and is modulated by several factors including (i)
      two sigma factors (sigma70 and sigmaE); (ii) the global regulator CRP; and (iii)
      the DnaA protein. Here, a further dissection of the rpoH regulatory region has
      revealed that an additional transcription control exists that appears to link
      rpoH expression to nucleoside metabolism. The cAMP-CRP complex and the CytR anti
      activator bind co-operatively to the promoter region forming a repression complex
      that overlaps the sigmaE-dependent P3 promoter and the sigma70-dependent P4 and
      P5 promoters. During steady-state growth conditions with glycerol as the carbon
      and energy source, transcription from P3, P4 and P5 is reduced approximately
      threefold by CytR, whereas transcription from the upstream promoter, P1, appears
      to be unaffected. Furthermore, in strains that slightly overproduce CytR,
      transcription from P3, P4 and P5 is reduced even further (approximately 10-fold),
      and repression can be fully neutralized by the addition of the inducer cytidine
      to the growth medium. In the induced state, P4 is the strongest promoter and,
      together with P3 and P5, it is responsible for most rpoH transcription (65-70%).
      At present, CytR has been shown to 'fine tune' transcription of two genes (rpoH
      and ppiA) that are connected with protein-folding activities. These findings
      suggest that additional assistance in protein folding is required under
      conditions in which CytR is induced (i.e. in the presence of nucleosides).

PMID- 9767578
TI  - Downregulation of Escherichia coli yfiD expression by FNR occupying a site at 
      93.5 involves the AR1-containing face of FNR.
AB  - The promoter of the FNR-activated yfiD gene of Escherichia coli has an unusual
      architecture because it contains two FNR sites, an arrangement usually associated
      with FNR-mediated repression. Investigation of yfiD promoter derivatives with
      altered FNR sites revealed that occupation of the far upstream FNR site (FNR II)
      downregulated expression, despite the presence of a FNR dimer activating
      expression from the promoter proximal site (FNR I). Transcript mapping by primer
      extension, and mutagenesis of potential -10 elements, indicated that yfiD
      expression is driven from a single FNR-dependent promoter with FNR sites at -40.5
      (FNR I) and -93.5 (FNR II). However, yfiD mRNA is processed in stationary-phase
      cultures independently of rne, rpoS, ihfA and fis to yield transcripts lacking 12
      and 21 bases from their respective 5' ends. Single amino acid substitutions (G74-
      >C, F92-->S, A95-->P, R184-->P, P188-->A or L193-->P) in the surface of FNR that
      contains activating region 1 (AR1 contacts the alpha-subunit of RNA polymerase to
      promote transcription activation) reduced the inhibitory effect of FNR at FNR II,
      indicating that this region of the protein may have a role in repression as well
      as activation. The FNR variant F92-->S was notable because, although it activated
      transcription of yfiD (two FNR sites), it was unable to activate transcription
      from model Class I and II promoters, which contain only a single FNR site.

PMID- 9767577
TI  - A novel mechanism for upregulation of the Escherichia coli K-12 hmp
      (flavohaemoglobin) gene by the 'NO releaser', S-nitrosoglutathione: nitrosation
      of homocysteine and modulation of MetR binding to the glyA-hmp intergenic region.
AB  - The flavohaemoglobin gene, hmp, of Escherichia coli is upregulated by nitric
      oxide (NO) in a SoxRS-independent manner. We now show that hmp expression is also
      upregulated by S-nitrosoglutathione (GSNO, widely used as an NO releaser) and
      sodium nitroprusside (SNP, which is a NO+ donor). Elevated homocysteine (Hcy)
      levels, achieved either by adding Hcy extracellularly or using metE mutants,
      decreased hmp expression. Conversely, metC mutants (defective in Hcy synthesis)
      had higher levels of hmp expression. Mutations in metR abolished hmp induction by
      GSNO and SNP, and hmp expression became insensitive to Hcy. We propose that the
      previously documented modulation by Hcy of MetR binding to the glyA-hmp
      intergenic regulatory region regulates hmp transcription. Although two MetR
      binding sites are present in this region, only the higher affinity site proximal
      to hmp is required for hmp induction by GSNO and SNP. GSNO and SNP react with Hcy
      in vitro under physiologically relevant conditions of pH and temperature
      generating S-nitrosohomocysteine, although in the latter case this would be co
      ordinated to the Fe in SNP as a stable species. The free S-nitrosocysteine
      generated in the reaction with GSNO breaks down to release NO more readily than
      via homolysis of GSNO. As GSNO and SNP upregulate hmp similarly, the NO released
      in the former case on reaction with homocysteine cannot be involved in hmp
      regulation.

PMID- 9767579
TI  - The positive inside rule is not determined by the polarity of the delta psi
      (transmembrane electrical potential)

PMID- 9767580
TI  - Competence regulons, genomics and streptococci.

PMID- 9767581
TI  - Non-specific, general and multiple stress resistance of growth-restricted
      Bacillus subtilis cells by the expression of the sigmaB regulon.
AB  - Bacillus subtilis cells respond almost immediately to different stress conditions
      by increasing the production of general stress proteins (GSPs). The genes
      encoding the majority of the GSPs that are induced by heat, ethanol, salt stress
      or by starvation for glucose, oxygen or phosphate belong to the sigmaB-dependent
      general stress regulon. Despite a good understanding of the complex regulation of
      the activity of sigmaB and knowledge of a very large number of general stress
      genes controlled by sigmaB, first insights into the physiological role of this
      nonspecific stress response have been obtained only very recently. To explore the
      physiological role of this reguIon, we and others identified sigmaB-dependent
      general stress genes and compared the stress tolerance of wild-type cells with
      mutants lacking sigmaB or general stress proteins. The proteins encoded by sigmaB
      dependent general stress genes can be divided into at least five functional
      groups that most probably provide growth-restricted B. subtilis cells with a
      multiple stress resistance in anticipation of future stress. In particular, sigB
      mutants are impaired in non-specific resistance to oxidative stress, which
      requires the sigmaB-dependent dps gene encoding a DNA-protecting protein.
      Protection against oxidative damage of membranes, proteins or DNA could be the
      most essential component of sigmaB mediated general stress resistance in growth
      arrested aerobic gram-positive bacteria. Other general stress genes have both a
      sigmaB-dependent induction pathway and a second sigmaB-independent mechanism of
      stress induction, thereby partially compensating for a sigmaB deficiency in a
      sigB mutant. In contrast to sigB mutants, null mutations in genes encoding those
      proteins, such as cIpP or cIpC, cause extreme sensitivity to salt or heat.

PMID- 9767582
TI  - Timing, self-control and a sense of direction are the secrets of multicopy
      plasmid stability.
AB  - Multicopy plasmids of Escherichia coli are distributed randomly at cell division
      and, as long as copy number remains high, plasmid-free cells arise only rarely.
      Copy number variation is minimized by plasmid-encoded control circuits, and the
      limited data available suggest that deviations are corrected efficiently under
      most circumstances. However, plasmid multimers confuse control circuits, leading
      to copy number depression. To make matters worse, multimers out-replicate
      monomers and accumulate clonally within the culture, creating a subpopulation of
      cells with a significantly increased rate of plasmid loss. Multimers of natural
      multicopy plasmids, such as ColE1, are resolved to monomers by a site-specific
      recombination system (Xer-cer) whose activity is limited to intramolecular
      recombination. Recombination requires the heterodimeric XerCD recombinase plus
      two accessory proteins (ArgR and PepA), which activate recombination and prevent
      intermolecular events. Evidence is accumulating that Xer-cer recombination is
      relatively slow, and there is a risk that cells might divide before multimer
      resolution is complete. The Rcd transcript encoded within cer may solve this
      problem by preventing the division of multimer-containing cells. Working in
      concert, the triumvirate of copy number control, multimer resolution and cell
      division control achieve an extremely high fidelity of plasmid maintenance.

PMID- 9767583
TI  - A mechanism for simultaneous sensing of aspartate and maltose by the Tar
      chemoreceptor of Escherichia coli.
AB  - The Tar chemoreceptor of Escherichia coli exhibits partial sensory additivity.
      Tar can mediate simultaneous responses to two disparate ligands, aspartate and
      substrate-loaded maltose-binding protein (MBP). To investigate how one receptor
      generates concurrent signals to two stimuli, ligand-binding asymmetry was imposed
      on the rotationally symmetric Tar homodimer. Mutations causing specific defects
      in aspartate or maltose chemotaxis were introduced pairwise into plasmid-borne
      tar genes. The doubly mutated tar genes did not restore aspartate or maltose
      chemotaxis in a strain containing a chromosomal deletion of tar (delta tar).
      However, when Tar proteins with complementing sets of mutations were co-expressed
      from compatible plasmids, the resulting heterodimeric receptors enabled delta tar
      cells to respond to aspartate or maltose. The effect of one attractant on the
      response to the other depended on the relative orientations of the functional
      binding sites for aspartate and MBP. When the sites were in the 'same'
      orientation, saturating levels of one attractant strongly inhibited chemotaxis to
      the other. In the 'opposite' orientation, such inhibitory effects were
      negligible. These data demonstrate that opposing subunits of Tar can transmit
      signals to aspartate and maltose independently if the ligands are restricted to
      the 'opposite' binding orientation. When aspartate and MBP bind in the 'same'
      orientation, they compete for signalling through one subunit. In the wild-type
      Tar dimer, aspartate and MBP can bind in either the 'same' or the 'opposite'
      orientation, a freedom that can explain the partial additivity of the aspartate
      and maltose responses that is seen with tar+ cells.

PMID- 9767584
TI  - Functional conservation of the effector protein translocators PopB/YopB and
      PopD/YopD of Pseudomonas aeruginosa and Yersinia pseudotuberculosis.
AB  - Virulent Yersinia species cause systemic infections in rodents, and Y. pestis is
      highly pathogenic for humans. Pseudomonas aeruginosa, on the other hand, is an
      opportunistic pathogen, which normally infects only compromised individuals.
      Surprisingly, these pathogens both encode highly related contact-dependent
      secretion systems for the targeting of toxins into eukaryotic cells. In Yersinia,
      YopB and YopD direct the translocation of the secreted Yop effectors across the
      target cell membrane. In this study, we have analysed the function of the YopB
      and YopD homologues, PopB and PopD, encoded by P. aeruginosa. Expression of the
      pcrGVHpopBD operon in defined translocation-deficient mutants (yopB/yopD) of
      Yersinia resulted in complete complementation of the cell contact-dependent, YopE
      induced cytotoxicity of Y. pseudotuberculosis on HeLa cells. We demonstrated that
      the complementation fully restored the ability of Y. pseudotuberculosis to
      translocate the effector molecules YopE and YopH into the HeLa cells. Similar to
      YopB, PopB induced a lytic effect on infected erythrocytes. The lytic activity
      induced by PopB could be prevented if the erythrocytes were infected in the
      presence of sugars larger than 3 nm in diameter, indicating that PopB induced a
      pore of similar size compared with that induced by YopB. Our findings show that
      the contact-dependent toxin-targeting mechanisms of Y. pseudotuberculosis and P.
      aeruginosa are conserved at the molecular level and that the translocator
      proteins are functionally interchangeable. Based on these similarities, we
      suggest that the translocation of toxins such as ExoS, ExoT and ExoU by P.
      aeruginosa across the eukaryotic cell membrane occurs via a pore induced by PopB.

PMID- 9767585
TI  - The identification of Mycobacterium marinum genes differentially expressed in
      macrophage phagosomes using promoter fusions to green fluorescent protein.
AB  - Mycobacterium marinum, like Mycobacterium tuberculosis, is a slow-growing
      pathogenic mycobacteria that is able to survive and replicate in macrophages.
      Using the promoter-capture vector pFPV27, we have constructed a library of 200
      1000 bp fragments of M. marinum genomic DNA inserted upstream of a promoterless
      green fluorescent protein (GFP) gene. Only those plasmids that contain an active
      promoter will express GFP. Macrophages were infected with this fusion library,
      and phagosomes containing fluorescent bacteria were isolated. Promoter constructs
      that were more active intracellularly were isolated with a fluorescence-activated
      cell sorter, and inserts were partially sequenced. The promoter fusions expressed
      intracellularly exhibited homology to mycobacterial genes encoding, among others,
      membrane proteins and biosynthetic enzymes. Intracellular expression of GFP was 2
      20 times that of the same clones grown in media. Several promoter constructs were
      transformed into Mycobacterium smegmatis, Mycobacterium bovis BCG and
      Mycobacterium tuberculosis. These constructs were positive for GFP expression in
      all mycobacterial strains tested. Sorting fluorescent bacteria in phagosomes
      circumvents the problem of isolating a single clone from macrophages, which may
      contain a mixed bacterial population. This method has enabled us to isolate 12 M.
      marinum clones that contain promoter constructs differentially expressed in the
      macrophage.

PMID- 9767586
TI  - Preprotein transfer to the Escherichia coli translocase requires the co-operative
      binding of SecB and the signal sequence to SecA.
AB  - In Escherichia coli, precursor proteins are targeted to the membrane-bound
      translocase by the cytosolic chaperone SecB. SecB binds to the extreme carboxy
      terminus of the SecA ATPase translocase subunit, and this interaction is promoted
      by preproteins. The mutant SecB proteins, L75Q and E77K, which interfere with
      preprotein translocation in vivo, are unable to stimulate in vitro translocation.
      Both mutants bind proOmpA but fail to support the SecA-dependent membrane binding
      of proOmpA because of a marked reduction in their binding affinities for SecA.
      The stimulatory effect of preproteins on the interaction between SecB and SecA
      exclusively involves the signal sequence domain of the preprotein, as it can be
      mimicked by a synthetic signal peptide and is not observed with a mutant
      preprotein (delta8proOmpA) bearing a non-functional signal sequence.
      Delta8proOmpA is not translocated across wild-type membranes, but the
      translocation defect is suppressed in inner membrane vesicles derived from a
      prIA4 strain. SecB reduces the translocation of delta8proOmpA into these vesicles
      and almost completely prevents translocation when, in addition, the SecB binding
      site on SecA is removed. These data demonstrate that efficient targeting of
      preproteins by SecB requires both a functional signal sequence and a SecB binding
      domain on SecA. It is concluded that the SecB-SecA interaction is needed to
      dissociate the mature preprotein domain from SecB and that binding of the signal
      sequence domain to SecA is required to ensure efficient transfer of the
      preprotein to the translocase.

PMID- 9767587
TI  - Deletion analysis of MotA and MotB, components of the force-generating unit in
      the flagellar motor of Salmonella.
AB  - MotA and MotB are cytoplasmic membrane proteins that form the force-generating
      unit of the flagellar motor in Salmonella typhimurium and many other bacteria.
      Many missense mutations in both proteins are known to cause slow motor rotation
      (slow-motile phenotype) or no rotation at all (non-motile or paralysed
      phenotype). However, large stretches of sequence in the cytoplasmic regions of
      MotA and in the periplasmic region of MotB have failed to yield these types of
      mutations. In this study, we have investigated the effect of a series of 10-amino
      acid deletions in these phenotypically silent regions. In the case of MotA, we
      found that only the C-terminal 5 amino acids were completely dispensable; an
      adjacent 10 amino acids were partially dispensable. In the cytoplasmic loop
      region of MotA, deletions made the protein unstable. For MotB, we found that two
      large segments of the periplasmic region were dispensable: the results with
      individual deletions showed that the first consisted of six deletions between the
      sole transmembrane span and the peptidoglycan binding motif, whereas the second
      consisted of four deletions at the C-terminus. We also found that deletions in
      the MotB cytoplasmic region at the N-terminus impaired motility but did not
      abolish it. Further investigations in MotB were carried out by combining
      dispensable deletion segments. The most extreme version of MotB that still
      retained some degree of function lacked a total of 99 amino acids in the
      periplasmic region, beginning immediately after the transmembrane span. These
      results indicate that the deleted regions in the MotA cytoplasmic loop region are
      essential for stability; they may or may not be directly involved in torque
      generation. Part of the MotA C-terminal cytoplasmic region is not essential for
      torque generation. MotB can be divided into three regions: an N-terminal region
      of about 30 amino acids in the cytoplasm, a transmembrane span and about 260
      amino acids in the periplasm, including a peptidoglycan binding motif. In the
      periplasmic region, we suggest that the first of the two dispensable stretches in
      MotB may comprise part of a linker between the transmembrane span of MotB and its
      attachment point to the peptidoglycan layer, and that the length or specific
      sequence of much of that linker sequence is not critical. About 40 residues at
      the C-terminus are also unimportant.

PMID- 9767588
TI  - Investigation of mycobacterial recA function: protein introns in the RecA of
      pathogenic mycobacteria do not affect competency for homologous recombination.
AB  - The recA locus of pathogenic mycobacteria differs from that of non-pathogenic
      species in that it contains large intervening sequences termed protein introns or
      inteins that are excised by an unusual protein-splicing reaction. In addition, a
      high degree of illegitimate recombination has been observed in the pathogenic
      Mycobacterium tuberculosis complex. Homologous recombination is the main
      mechanism of integration of exogenous nucleic acids in M. smegmatis, a non
      pathogenic mycobacterium species that carries an inteinless RecA and is amenable
      to genetic manipulations. To investigate the function of recA in mycobacteria,
      recA- strains of M. smegmatis were generated by allelic exchange techniques.
      These strains are characterized (i) by increased sensitivity towards DNA-damaging
      agents [ethylmethylsulphonate (EMS), mitomycin C, UV irradiation] and (ii) by the
      inability to integrate nucleic acids by homologous recombination. Transformation
      efficiencies using integrative or replicative vectors were not affected in recA-
      mutants, indicating that in mycobacteria RecA does not affect plasmid uptake or
      replication. Complementation of the recA- mutants with the recA from M.
      tuberculosis restored resistance towards EMS, mitomycin C and UV irradiation.
      Transformation of the complemented strains with suicide vectors targeting the
      pyrF gene resulted in numerous allelic exchange mutants. From these data, we
      conclude that the intein apparently does not interfere with RecA function, i.e.
      with respect to competency for homologous recombination, the RecAs from
      pathogenic and non-pathogenic mycobacteria are indistinguishable.

PMID- 9767589
TI  - De novo fatty acid synthesis is required for establishment of cell type-specific
      gene transcription during sporulation in Bacillus subtilis.
AB  - A hallmark of sporulation of Bacillus subtilis is the formation of two distinct
      cells by an asymmetric septum. The developmental programme of these two cells
      involves the compartmentalized activities of sigmaE in the larger mother cell and
      of sigmaF in the smaller prespore. A potential role of de novo lipid synthesis on
      development was investigated by treating B. subtilis cells with cerulenin, a
      specific inhibitor of fatty acid biosynthesis. These experiments demonstrated
      that spore formation requires de novo fatty acid synthesis at the onset of
      sporulation. The transcription of the sporulation genes that are induced before
      the formation of two cell types or that are under the exclusive control of sigmaF
      occurred in the absence of fatty acid synthesis, as monitored by spo-lacZ
      fusions. However, expression of lacZ fusions to genes that required activation of
      sigmaE for transcription was inhibited in the absence of fatty acid synthesis.
      The block in sigmaE-directed gene expression in cerulenin-treated cells was
      caused by an inability to process pro-sigmaE to its active form. Electron
      microscopy revealed that these fatty acid-starved cells initiate abnormal polar
      septation, suggesting that de novo fatty acid synthesis may be essential to
      couple the activation of the mother cell transcription factors with the formation
      of the differentiating cells.

PMID- 9767590
TI  - Crl stimulates RpoS activity during stationary phase.
AB  - RpoS, an alternative primary sigma factor, has been shown to be regulated at
      multiple levels, including transcription, translation and protein stability.
      Here, we present evidence that suggests that RpoS is regulated at yet another
      level by the product of the crl gene. The crl gene was first thought to encode
      the major curlin subunit of curli (curli are surface structures that are induced
      by growth into stationary phase under conditions of low osmolarity and low
      temperature). Later, it was determined that crl actually contributes in a
      positive fashion to stimulate transcription of csgBA, the true locus encoding for
      the major subunit of curli. RpoS is also required for normal stationary-phase
      induction of csgBA. We found that lesions in crl, like lesions in rpoS, cause
      increased transcription of ompF during stationary phase. Taken together, these
      observations prompted us to analyse the effects of crl on an additional RpoS
      regulated phenomenon. We found that a crl null allele influences expression of
      RpoS-regulated genes in a fashion similar to an rpoS null allele. Genetic
      evidence suggests that crl and rpoS function in a single pathway and that Crl
      functions upstream, or in concert with, RpoS. Although the effects of Crl on RpoS
      regulated genes is entirely dependent on the integrity of RpoS, the presence of a
      crl null allele does not decrease the level of RpoS protein. Thus, we propose
      that Crl stimulates the activity of the RpoS regulon by stimulating RpoS activity
      during stationary phase.

PMID- 9767591
TI  - An ExeAB complex in the type II secretion pathway of Aeromonas hydrophila: effect
      of ATP-binding cassette mutations on complex formation and function.
AB  - The energy-dependent secretion of aerolysin by Aeromonas hydrophila requires the
      ExeA and ExeB proteins. An 85 kDa complex containing the two proteins was
      identified in wild-type cells but not in cells producing either protein alone.
      Radiolabelling followed by cross-linking, immunoprecipitation and then reduction
      of the cross-links confirmed the presence of the two proteins in the same
      complex. The complex could also be extracted intact from cell membranes with non
      ionic detergents. A G229D substitution in the kinase-3a motif of ExeA strongly
      reduced the level of aerolysin secretion, as did the replacement of the invariant
      Lys of the kinase-1a motif (K56) with Arg. The G229D mutant contained very little
      of the ExeA-ExeB complex, but overexpression of the mutant complex until wild
      type levels were achieved allowed normal secretion. In contrast, the K56R
      mutation had no effect on complex formation, but normal secretion levels occurred
      only when there was a far greater amount of the complex present. These results
      are consistent with a model in which binding of ATP by ExeA is required for ExeA
      ExeB complex formation, while hydrolysis is required for its function in
      secretion once established.

PMID- 9767592
TI  - The pilH gene encodes an ABC transporter homologue required for type IV pilus
      biogenesis and social gliding motility in Myxococcus xanthus.
AB  - Type IV pilus genes have been shown to be required for social gliding motility in
      Myxococcus xanthus. We report the discovery of four additional pil genes: pilD, a
      homologue of type IV prepilin leader peptidases; and pilG, pilH and pilI, which
      have no known homologues in other type IV pilus systems. pilH encodes an ATP
      binding cassette (ABC) transporter homologue, the first such homologue to be
      required for the biogenesis of any bacterial pilus type. pilG and pilI are co
      transcribed with pilH and appear to be functionally related to pilH. Null mutants
      of pilG, pilH and pilI all lack social motility, are deficient in pilus
      production, have elevated sporulation efficiencies and display similar
      developmental abnormalities. In addition, all three mutations reduced the amount
      of PilA found in the supernatant after cells were sedimented from liquid culture.
      We suggest that the products of these three genes form a single ABC exporter
      complex, in which pilI is an integral membrane protein with membrane-spanning
      domains, and pilG is an accessory factor. The complex may participate in pilus
      assembly and/or the export of PilA pilin.

PMID- 9767593
TI  - Identification of an amino-terminal substrate-binding domain in the Yersinia
      tyrosine phosphatase that is required for efficient recognition of focal adhesion
      targets.
AB  - YopH is a protein tyrosine phosphatase (PTP) that is delivered into host
      mammalian cells via a type III secretion pathway in pathogenic Yersinia species.
      Although YopH is a highly active PTP, it preferentially targets a subset of
      tyrosine-phosphorylated proteins in host cells, including p130Cas. Previous in
      vitro studies have indicated that the carboxy-terminal PTP domain contributes
      specificity to the interaction of YopH with substrates. However, it is not known
      if the PTP domain is sufficient for substrate recognition by YopH. Here, we have
      identified paxillin as an additional substrate of YopH in HeLa cells. In
      addition, we have identified a domain in the amino-terminal region of YopH that
      binds to both p130Cas and paxillin and is required for the efficient recognition
      of substrates by the wild-type enzyme. This 'substrate-binding' domain exhibits a
      ligand specificity that is similar to that of the Crk Src homology 2 (SH2)
      domain, and it binds substrates directly in a phosphotyrosine-dependent manner.
      The substrate-binding domain of YopH may represent a novel type of protein
      protein interaction module, as it lacks significant sequence similarity with any
      known SH2 or phosphotyrosine-binding (PTB) domain.

PMID- 9767594
TI  - Toxin binding site of the diphtheria toxin receptor: loss and gain of diphtheria
      toxin binding of monkey and mouse heparin-binding, epidermal growth factor-like
      growth factor precursors by reciprocal site-directed mutagenesis.
AB  - The transmembrane precursor of the monkey (Mk) heparin-binding, epidermal growth
      factor-like growth factor (proHB-EGF) functions as a diphtheria toxin (DT)
      receptor, whereas the mouse (Ms) precursor does not. Previously, using chimeric
      Ms/Mk precursors, we have shown that DT resistance of cells bearing Ms proHB-EGF
      may be accounted for by several amino acid substitutions between residues 122 and
      148 within the EGF-like domain and that Glu-141 is an important amino acid
      residue for DT binding. In this study, reciprocal site-directed mutagenesis was
      performed on the major non-conserved residues in the region of 122-148, alone or
      in combination, between Mk and Ms precursors to identify more precisely which
      amino acid residues are important for DT binding. Two approaches were used. The
      first, more traditional approach was to destroy DT sensitivity and binding of Mk
      proHB-EGF by substitution(s) with the corresponding Ms residue(s). From the
      single mutations, the greatest loss of DT sensitivity was observed with Mk/Glu
      141His (approximately 4000-fold) and the next greatest with Mk/Ile-133Lys
      (approximately fourfold). The double mutations Mk/Leu-127Phe/Glu-141His, Mk/Ile
      133Lys/Glu-141His and Mk/His-135Leu/Glu-141His resulted in complete toxin
      resistance (> 100000-fold). The second approach, both novel and complementary,
      was to gain DT binding and sensitivity of Ms proHB-EGF by substitution(s) with
      the corresponding Mk residue(s). Surprisingly, the single mutation Ms/His-141Glu
      resulted in the gain of moderate DT sensitivity (> 260-fold). The double mutation
      Ms/Lys-133Ile/His-141Glu and the triple mutation Ms/Lys-133Ile/Leu-135His/His
      141Glu resulted in a progressive gain in toxin sensitivity (> 4700-fold and
      >16000-fold respectively) and affinity. This triple mutant cell line is
      essentially as sensitive (IC50 = 3.1 ng ml(-1)) as the highly toxin-sensitive
      monkey Vero cell line (IC50 = 4 ng ml(-1)), indicating that these three Mk
      residues enable the Ms proHB-EGF to act as a fully functional DT receptor. Taken
      together, these results indicate that Glu-141 plays the most critical role in DT
      binding and sensitivity and that two additional amino acid residues, Ile-133 and
      His-135, also play significant roles.

PMID- 9767595
TI  - Penicillin tolerance genes of Streptococcus pneumoniae: the ABC-type manganese
      permease complex Psa.
AB  - Downregulation of the major autolysin in Streptococcus pneumoniae leads to
      penicillin tolerance, a feature that is characterized by the ability to survive
      but not grow in the presence of antibiotic. Screening a library of mutants in
      pneumococcal surface proteins for the ability to survive 10x minimum inhibitory
      concentration (MIC) of penicillin revealed over 10 candidate tolerance genes. One
      such mutant contained an insertion in the known gene psaA, which is part of the
      psa locus. This locus encodes an ABC-type Mn permease complex. Sequence analysis
      of adjacent DNA extended the known genetic organization of the locus to include
      two new open reading frames (ORFs), psaB, which encodes an ATP-binding protein,
      and psaC, which encodes a hydrophobic transmembrane protein. Mutagenesis of psaB,
      psaC, psaA and downstream psaD resulted in penicillin tolerance. Defective
      adhesion and reduced transformation efficiency, as reported previously for a psaA
      mutant, were phenotypes shared by psaB-, psaC- and psaD- knockout mutants.
      Western blot analysis demonstrated that the set of mutants expressed RecA, but
      none of them showed translation of the autolysin gene, which is located
      downstream of recA. The addition of manganese (Mn) failed to correct the abnormal
      physiology. These results suggest that this ABC-type Mn permease complex has a
      pleiotropic effect on pneumococcal physiology including adherence and autolysis.
      These are the first genes suggested as being involved in triggering autolysin.
      The results raise the possibility that loss of function of PsaA, by vaccine
      induced antibody for instance, may promote penicillin tolerance.

PMID- 9767596
TI  - Sphingomyelin, glycosphingolipids and ceramide signalling in cells exposed to P
      fimbriated Escherichia coli.
AB  - Uropathogenic Escherichia coli attach to epithelial cells through P fimbriae that
      bind Galalpha1-4Galbeta-oligosaccharide sequences in cell surface
      glycosphingolipids. The binding of P-fimbriated E. coli to uroepithelial cells
      causes the release of ceramide, activation of the ceramide signalling pathway and
      a cytokine response in the epithelial cells. The present study examined the
      molecular source of ceramide in human kidney A498 cells exposed to P-fimbriated
      E. coli. Agonists such as TNF-alpha and IL-1beta released ceramide from
      sphingomyelin by the activation of endogenous sphingomyelinases and hydrolysis of
      sphingomyelin, and triggered an IL-6 response. P-fimbriated E. coli caused a
      slight increase in endogenous sphingomyelinase activity, but there was no
      associated sphingomyelin hydrolysis. Instead, the concentration of galactose
      containing glycolipids decreased. We propose that P-fimbriated E. coli differ
      from other activators of the ceramide pathway, in that release of ceramide is
      from receptor glycolipids and not from sphingomyelin. Receptor breakdown may be
      an efficient host defence strategy, as it reduces the concentration of cell
      surface receptors, releases soluble receptor analogues and activates an
      inflammatory response.

PMID- 9767597
TI  - Yeast gene YRR1, which is required for resistance to 4-nitroquinoline N-oxide,
      mediates transcriptional activation of the multidrug resistance transporter gene
      SNQ2.
AB  - We have cloned and characterized a Saccharomyces cerevisiae gene YRR1 that is
      important for resistance to the mutagen 4-nitroquinoline N-oxide (4-NQO). The
      wild-type YRR1 gene encodes a protein that contains a Zn(II)2Cys6-type zinc
      finger motif. Disruption of the YRR1 gene leads to hypersensitivity to 4-NQO. A
      dominant mutation (YRR1-1) that confers strong resistance to 4-NQO has been
      identified. Epistasis analysis demonstrated that 4-NQO resistances mediated by
      the YRR1 and YRR1-1 alleles require the presence of the SNQ2 gene that encodes a
      multidrug resistance ATP binding cassette superfamily protein responsible for 4
      NQO export. Northern blot analysis of SNQ2 mRNA levels indicated that Yrr1p is
      involved in basal and drug-induced transcriptional activation of SNQ2, whereas
      Pdr1p/Pdr3p transcription factors are mainly involved in basal SNQ2 expression.
      In the YRR1-1 mutant, the level of SNQ2 mRNA is constitutively elevated. These
      results establish that Yrr1p is important for 4-NQO resistance by mediating
      transcriptional activation of the SNQ2 gene in response to the stress imposed by
      4-NQO. The gain-of-function mutation of Yrr1-1p was attributable to the
      duplication of a 12-amino-acid sequence generated near the carboxy terminus.

PMID- 9767598
TI  - Essential monomer-monomer contacts define the minimal length for the N-terminus
      of RecA protein.

PMID- 9767599
TI  - Widespread production of AS-48-like bacteriocins in strains of Enterococcus
      faecalis?

PMID- 9767600
TI  - Identification, characterization and expression of Toxocara canis nematode
      polyprotein allergen TBA-1.
AB  - We have cloned the cDNA of TBA-1, the Nematode polyprotein allergen (NPA) of
      Toxocara canis and found it to be most similar to ABA-1, the Ascaris NPA, on the
      basis of amino acid sequence. We could study the antigenic properties of an E
      coli synthesized fusion protein prepared with the cloned gene since no
      glycosylation site was expected from the deduced amino acid sequence. Although no
      IgE responses to TBA-1 were detected, recombinant TBA-1 was differently
      recognized by serum IgG antibodies when the recombinant TBA-1 was directly
      adsorbed vs when immobilized via a streptavidin linkage on polystyrene microtitre
      wells. One group of sera recognized TBA-1 directly immobilized while the second
      only recognized TBA-1 immobilized via streptavidin linkage. The former were from
      rodents immunized with a Toxocara sp. adult worm extract while the latter were
      obtained from rodents infected with T. canis larva or immunized with a Anisakis
      simplex L3 larval extract. These observations suggest that the two in vivo forms
      of TBA-1 are expressed, but during different stages of the parasite's life cycle.

PMID- 9767601
TI  - Murine immune responses to Schistosoma haematobium and the vaccine candidate
      rSh28GST.
AB  - Longitudinal studies of Schistosoma haematobium infection in CBA mice revealed a
      progressive down-regulation of cellular immune responses, as measured by
      mitogenic and antigenic stimulation of in vitro lymphocyte cultures. Antigen
      stimulated production of the Th1 cytokine IFN-gamma by splenocytes increased
      progressively up to 14 weeks post infection, (four weeks after the onset of
      parasite egg production), before declining swiftly. Levels of the Th2 cytokine IL
      4 in the same cultures remained low until 14 weeks, after which they rose rapidly
      as IFN-gamma declined. High levels of IL-10 coincided with the peak in IFN-gamma
      production, suggesting a non Th2-restricted role for this cytokine. Both total
      and antigen-specific immunoglobulin production confirmed parasite egg deposition
      as being a major stimulus for host humoral responses. The S. haematobium
      infection failed to elicit detectable T cell responses to the antifecundity
      vaccine candidate rSh28GST. However, low levels of antibody were detectable in
      infected mouse serum and strong IgG and IgA production was induced by vaccination
      with rSh28GST plus adjuvant.

PMID- 9767602
TI  - Serum concentrations of sICAM-1, sE-, sP- and sL-selectins in patients with
      Schistosoma mansoni infection and association with disease severity.
AB  - Increased serum concentrations of soluble intercellular adhesion molecule-1
      (sICAM-1, CD54) and of soluble E- (CD62E), but not soluble P- (CD62P) and L-
      (CD62 L) selectins, were detected in Malagasy patients living in an hyperendemic
      focus of Schistosoma mansoni. Levels of sICAM-1 remained elevated for several
      months after treatment with praziquantel. Serum levels of ICAM-1, but not of
      other markers, were significantly correlated with the disease severity, as
      indicated by ultrasonographical data, and with some circulating fibrosis markers
      (at least hyaluronic acid). sICAM-1 level may reflect endothelial inflammatory
      reactions, probably harmful, in the liver and may be useful for monitoring
      morbidity evolution in schistosomiasis mansoni.

PMID- 9767603
TI  - Immunological properties of recombinant proteins of the transmission blocking
      vaccine candidate, Pfs48/45, of the human malaria parasite Plasmodium falciparum
      produced in Escherichia coli.
AB  - A precondition for the development of a transmission blocking vaccine based on
      the sexual stage-specific surface antigen Pfs48/45 of Plasmodium falciparum is
      its heterologous synthesis in a native state. Here we describe the production of
      recombinant Pfs48/45 in Escherichia coli. Two recombinant proteins, of which one
      is a glutathione-S-transferase fusion protein, were produced. Enzyme-linked
      immunosorbent assays showed that at least a subfraction of the recombinant
      proteins had a conformation capable of binding transmission blocking monoclonal
      antibodies. However, despite the fact that both proteins were very immunogenic,
      they did not induce transmission blocking immunity in mice or rabbits.
      Immunological studies with congenic mouse strains demonstrated that immune
      responses could be boosted with gametocyte extracts and were not restricted to a
      particular class II major histocompatibility complex haplotype.

PMID- 9767604
TI  - IgG subclass recognition of Loa loa antigens and their correlation with clinical
      status in individuals from Gabon.
AB  - In endemic areas for Loa loa, a significant percentage of actively infected
      individuals have no circulating microfilariae, an observation which implies the
      existence of a stage-specific immune response. In an attempt to define the
      immunological basis of the amicrofilaraemic state, the reactivity of antigens
      from adult, microfilariae and infective larvae of L. loa was examined by Western
      blotting with individual serum samples from four clinically defined groups (high
      microfilaraemic, low microfilaraemic, amicrofilaraemic and endemic controls)
      using IgG subclass-specific reagents and IgE. In the adult parasite, a complex of
      antigens at 28-31 kDa was exclusively recognized by IgG1 from amicrofilaraemic
      individuals and, to a lesser extent, by IgG1 from endemic controls. However, this
      complex of antigens was recognized by IgG4 antibodies in serum samples from all
      individuals, including microfilaraemics. A microfilarial antigen of 21 kDa was
      recognized by IgG1 antibodies present in serum from amicrofilaraemic, endemic
      control and low microfilaraemic individuals. Persons with high levels of
      microfilariae did not recognise this antigen. In both the L3 and the
      microfilariae, a ladder antigen with increments of 15 kDa was the main target of
      IgG4 antibodies in amicrofilaraemic and microfilaraemic individuals. IgE
      antibodies recognized more antigens in the microfilarial stage than in the adult
      of L3. These results suggest that immunological differences between clinically
      defined groups are associated with the recognition of different antigens or
      epitopes.

PMID- 9767605
TI  - Nitric oxide production in vervet monkeys (Cercopithecus aethiops) infected with
      Trypanosoma brucei.
AB  - A retrospective study of nitrate concentration in serum and cerebrospinal fluid
      (CSF) from vervet monkeys (Cercopithecus aethiops) infected with Trypanosoma
      brucei was undertaken. Serum nitrate was significantly elevated in parasitaemic
      animals. CSF nitrate detection correlated with the presence of parasites in the
      CNS. The results provide evidence for the production of nitric oxide (NO) in
      response to infection in a primate model of human African trypanosomiasis and
      provide the basis for the use of such a model in studies of the
      immunopathological effects of NO in human trypanosomiasis.

PMID- 9767606
TI  - Fc-binding molecules specific for human IgG1 and IgG3 are present in Echinococcus
      granulosus protoscoleces.
AB  - In this work we describe the presence of Fc-binding activity on the suckers and
      tegument of E. granulosus protoscoleces. A fraction (PSA-Fc+) from protoscolex
      somatic antigens was isolated by affinity chromatography on human Fc-gamma1
      Sepharose. Analysis by SDS-PAGE of PSA-Fc+ showed that it contained two major
      components. Using mouse F(ab')2-human Fc chimaeric monoclonal antibodies we
      verified that PSA-Fc+ bound mainly to human Fc-gamma1 and Fc-gamma3 isotypes. In
      addition, one of the components of PSA-Fc+ showed proteolytic activity. Both, Fc
      binding and proteolytic activities localized on the protoscolex surface, may play
      a relevant role in the host-parasite interaction.

PMID- 9767607
TI  - Microbicidal activity of eosinophils is associated with activation of the
      arginine-NO pathway.
AB  - In order to investigate the ability of rat peritoneal eosinophils to produce
      nitric oxide (NO) induced by cytokines in vitro, these cells were activated with
      several cytokines (IL-5, IL-8, Rantes, TNF-alpha, IFN-gamma) in association or
      not with LPS. Under these conditions, we were able to detect nitrite in the
      incubation medium when the eosinophils were stimulated with IFN-gamma or IL-8 in
      the presence of LPS. LPS alone also induced nitrite production. Significant
      levels of nitrite in the medium were already present after 12 h of stimulation
      and increased steadily within the next 48 h. Regarding NO synthase, its highest
      activity was achieved at 12 h after IFN-gamma/LPS stimulation. After this peak,
      the enzymatic activity reduced gradually to control levels 48 h after the
      stimulation. The simultaneous addition of the NO synthase inhibitor L-NIO (100
      microM) to the eosinophil suspension blocked nitrite production and NO synthase
      activity. On the other hand, neither IL-5, Rantes nor TNF-alpha were able to
      induce the release of nitrite in the presence or absence of LPS. To evaluate the
      microbicidal effect of these cells against the Leishmania parasite, eosinophils
      were infected with Leishmania major. It was observed that these cells were able
      to produce nitrite and to kill the parasite after activation with LPS/IFN-gamma.
      Moreover, L-NIO blocked this leishmanicidal activity and the nitrite production.
      Our results suggest that activated eosinophils release NO which is involved in
      their microbicidal activity against Leishmania major.

PMID- 9767608
TI  - Intranasal immunization with yeast-expressed 19 kD carboxyl-terminal fragment of
      Plasmodium yoelii merozoite surface protein-1 (yMSP119) induces protective
      immunity to blood stage malaria infection in mice.
AB  - Variable protection against malaria blood-stage infection has been demonstrated
      in mice following parenteral immunization with the highly conserved 19 kD
      carboxylterminal fragment of the merozoite surface protein-1 (MSP119) using
      CFA/IFA and other adjuvants. Here we show that intranasal immunization of BALB/C
      mice with yeast expressed Plasmodium yoelii MSP119 plus a mixture of native and
      recombinant cholera toxin B subunit, could induce serum MSP119-specific
      antibodies at titres ranging from 20 000 to 2 560 000. The Ig subclass responses
      were predominantly G1 and G2b. Intranasal immunization led to protection
      following challenge (peak parasitaemia < 1%) in mice with the highest MSP119
      specific titre (>/= 640 000). In two of the three protected mice, a peak
      parasitaemia of 0.1%-1% was followed by a boost of the antibody response whereas
      one of the three protected mice did not boost its antibody response after a peak
      parasitaemia of 0.02%. In unprotected mice, antibody levels rose, then fell,
      following the detection of parasites in the peripheral blood. CD4+ T cell
      depletion abrogated the ability of the mice to boost their antibody response
      following challenge. These data demonstrate the potential for intranasal
      immunization with MSP119 to protect against malaria.

PMID- 9767609
TI  - Trypanosoma congolense infection of trypanotolerant N'Dama (Bos taurus) cattle is
      associated with decreased secretion of nitric oxide by interferon-gamma-activated
      monocytes and increased transcription of interleukin-10.
AB  - The mechanisms whereby trypanotolerant N'Dama cattle control infection with
      Trypanosoma congolense are unknown. Previous studies have suggested that the
      monocytes of N'Dama cattle are more highly activated during infection than those
      of trypanosusceptible Boran cattle. However, we have recently reported that the
      monocytes of Boran cattle have a reduced capacity to secrete nitric oxide during
      trypanosome infection. We therefore evaluated the production of nitric oxide by
      monocytes of trypanotolerant N'Dama cattle infected with T. congolense in
      response to interferon-gamma, bacterial lipopolysaccharide or trypanosome
      antigens. Interferon-gamma-induced nitric oxide production was decreased between
      days 25 and 76 of infection, while lipopolysaccharide-induced secretion of nitric
      oxide was increased at days 13 and again at day 76 post-infection. Trypanosome
      antigens did not elicit nitric oxide production. Analysis of interleukin-10 mRNA
      transcription in peripheral blood leucocytes revealed an increase at time points
      that coincided with decreased interferon-gamma-induced nitric oxide synthesis. In
      contrast, interferon-gamma mRNA expression was not changed during infection while
      tumour necrosis factor-alpha was slightly reduced at day 32 post-infection.
      Recombinant interleukin-10 suppressed interferon-gamma-induced nitric oxide and
      tumour necrosis factor-alpha secretion, but not lipopolysaccharide-induced nitric
      oxide secretion in cultures of peripheral blood mononuclear cells and monocytes
      of uninfected cattle. These results suggest that the nitric oxide response of
      monocytes to IFN-gamma but not lipopolysaccharide, is suppressed during
      infection. The kinetics of the upregulation of interleukin-10 and its biological
      activity indicate a possible association with the depression of nitric oxide
      production and control of tumour necrosis factor-alpha.

PMID- 9767610
TI  - T cell responses in coinfection with Onchocerca volvulus and the human
      immunodeficiency virus type 1.
AB  - Onchocerca volvulus and the human immunodeficiency virus (HIV) are two
      immunocompromising infectious agents of major public health concern in Uganda. To
      examine the effect of coinfection with O. volvulus and HIV on cellular immune
      responses, lymphocyte proliferative responses and cytokine production of
      peripheral blood mononuclear cells (PBMC) from persons infected with O. volvulus
      with and without HIV type 1 infection were compared. Proliferation of PBMC to PHA
      and tuberculin (PPD) in coinfection was less (P = 0.08, P < 0.01) than in O.
      volvulus infection. O. volvulus extract stimulated lymphocyte proliferation in
      microfilaria-negative and HIV-negative O. volvulus infection while only an
      inconspicuous response was observed in microfilaria-negative coinfection. After
      stimulation of PBMC with PPD, the production of interferon-gamma (IFN-gamma),
      interleukin (IL)-4 and IL-5-demonstrated in O. volvulus infection-were reduced in
      coinfection with HIV (P < 0.01). While both groups failed to produce IFN-gamma in
      response to O. volvulus extract, only O. volvulus infected persons generated
      pronounced IL-5 and low IL-4 levels (0.01 > P = 0.02). The cellular immune
      responses in coinfection suggested an HIV-related lack of specific reactivity to
      O. volvulus antigen and impairment of IL-4 and IL-5 production in addition to the
      lack of IFN-gamma response on antigenic stimulation.

PMID- 9767611
TI  - Amelioration of virulent Babesia bovis infection in calves by administration of
      the nitric oxide synthase inhibitor aminoguanidine.
AB  - Calves undergoing initial infection with a virulent strain of the haemoprotozoan
      parasite Babesia bovis were treated with aminoguanidine (AG), an inhibitor of the
      inducible form of nitric oxide synthase (iNOS). The mean maximum parasitaemia of
      the AG treated calves was significantly lower than that of the control cattle. In
      addition, the febrile response and decrease in packed cell volume (PCV) observed
      during acute infection were significantly ameliorated in the AG treated cattle
      relative to the controls. However, AG had no effect on the multiplication of B.
      bovis in the microaerophilous stationary-phase (MASP) in-vitro culture system.
      These results provide evidence of a role for nitric oxide (NO) produced in
      response to acute infection in the pathology of bovine babesiosis.

PMID- 9767613
TI  - Non-surgical therapy for patients with advanced non-small cell lung cancer.
AB  - Advanced non-small cell lung cancer (NSCLC) denotes those of TNM stage III and
      IV. NSCLC has its specific characteristics in respect of oncological behaviour,
      molecular biology, sensitivity to chemotherapy (CT) and radiotherapy (RT), and
      requires different therapeutic strategies in comparison with small cell lung
      cancer. The therapies include: (1) surgery in combination with new effective
      drugs is resulted in improved RR from 15% a decade ago to 40-60% today. Cisplatin
      (C-DDP) is the most attractive drug in the treatment of NSCLC, in lengthening the
      life-span of Stage IV NSCLC patients and as an indispensable sensitizer in RT.
      Taxinol, Gemcitabine (GEM), Navelbine (NVB), Edatrexate (ETX), CPT-11 and high
      dose Epirubicin (EPI HD) are recommended as new effective drugs. Response rates
      recently reported for the combination CT with the drugs mentioned above for NSCLC
      are from 30-65%, and with 8-42 weeks of MST. Induction or neoadjuvant therapies
      for advanced NSCLC, with 40-69% of RR, 25-29% of complete resection rate, 8-34%
      of CR and 17-45% of one year SR are reviewed. Eight random studies comparing MST
      between CT with C-DDP and best supportive care for NSCLC are statistically
      significant. (2) RT for Stage III NSCLC with 2 year and 5 year survivals of 20
      and 5% respectively. Although such outcome is hardly acceptable, RT sensitizer,
      modified RT techniques and chemoradiotherapy (CRT) are imperative to improve the
      effect of RT in advanced NSCLC. Clinical literature suggest that CRT is better
      than RT, though without marked difference. Further studies and sufficient follow
      up are necessary to judge the efficacy in terms of long-term survival and toxic
      reaction. (3) Biological therapy: gene therapy of NSCLC is still in the
      experimental and developmental stage. Of biological response modifier (BRM),
      alpha IFN in 11 cases of NSCLC with RR of 9% and MST of 14 months, IL-2 and LAK
      cell treatment in 11 cases with RR of 9% and MST of 18 months are reported.
      Instillation of BRM such as IL-2 or alpha-IFN into the pleura after drainage of
      cancerous effusion has been reported as the most effective for those whose RR is
      of 80-90% and the clinical response time is fairly long. Hematological cytokine
      as a protective adjuvant therapy against CT/RT toxicity makes high dose of CT
      possible and raises the response and patient tolerance. In multimodality therapy,
      it plays an important role to reduce post CT infection and septicemia.

PMID- 9767612
TI  - Chemotherapy for advanced (stage IIIB and stage IV) non-small cell lung cancer:
      the Hong Kong perspective.
AB  - Non-small cell lung cancer (NSCLC) accounts for about 80% of all primary lung
      cancers, and 60% of cases present as advanced stages IIIB and IV disease.
      Traditionally, treatment of stages IIIB and IV disease was only symptomatic
      (including radiotherapy) and supportive care, and cytotoxic chemotherapy was
      relatively ineffective. Our initial clinical trials, using MACC, FuAM, FAM, Hi
      FAM and cisplatin-VP16, gave response rates of 5-20% and a stabilization rate of
      7-25%, with no impact on median survival. Our most recent chemotherapy regimen
      MIP (mitomycin-C, ifosfamide and cisplatin) proved to be more effective with a
      44% response rate and a 28% stabilzation rate, and produced a significantly
      longer median survival (32 weeks) than best supportive care alone (19.5 weeks, P<
      0.05). The response rate further increased to 62.5% with dose intensification and
      GM-CSF support. Chemotherapy can now be recommended to motivated, well-informed
      patients with good performance status in institutions with experience in cancer
      chemotherapy on a protocol basis. The most recent addition of new effective
      cytotoxic agents such as paclitaxel, docetaxel, gemitabine and vinorelbine gave
      promising results in NSCLC, and optimal combinations and dose schedules are being
      defined by multicentred studies.

PMID- 9767614
TI  - Non-surgical therapy for the patients with advanced non-small cell lung cancer.
AB  - Radiation therapy (RT) and chemotherapy have been the two main treatment
      modalities for advanced non-small cell lung cancer (NSCLC). New techniques in RT,
      including hyperfractination and 3-dimensional conformal RT (3-DCRT), have changed
      conventional RT, which has been regarded as standard modality for locally
      advanced NSCLC. Introduction of cisplatin into chemotherapeutic regimens for
      NSCLC has changed the status of chemotherapy to standard therapy for patients
      with stage IV or stage IIIb with effusion. Radiation therapy or chemotherapy
      alone have already showed their limitations, even although they could improve the
      survival of NSCLC patients. Combined treatments with these two have become
      powerful alternatives for patients with unresectable and locally advanced NSCLC.
      Sequential or concurrent chemoradiotherapy could improve the response rate and
      survival rate without a remarkable increase in toxicities. Gene therapy is a
      novel therapeutic approach based on molecular oncology and tumour immunology. The
      practical contribution of gene therapy to clinical oncology is still minimal.
      From the research data, gene therapy has shown its potential to become a new
      treatment modality or to lead us to as yet undiscovered novel approaches to the
      treatment of lung cancer.

PMID- 9767615
TI  - Non-surgical treatment of advanced non-small cell lung cancer in Japan.
AB  - The cisplatin-based conventional combination chemotherapy has been shown to
      prolong survival of patients with advanced non-small cell lung cancer (NSCLC),
      but the treatment effect is only modest and of little clinical significance.
      Several promising 'new-generation' anti-cancer drugs, such as taxanes,
      vinorelbine, gemcitabine and irinotecan, have offered both chance and challenge
      to develop effective chemotherapy against NSCLC. In Japan, large-scale phase III
      trials of cisplatin-irinotecan combination regimen vs. conventional chemotherapy
      have been conducted; patient accrual has been completed and the final results
      will be presented in a couple of years. Other new agents will also be available
      by the end of 1999, and it will be our important task to evaluate those drugs
      efficiently. The current standard treatment strategy against unresectable stage
      III NSCLC is chemo- radiotherapy. However, there remain many questions to be
      answered through well-designed clinical trials. Those include optimal timing and
      schedule of the chemoradiotherapy, dose and fractionation of radiation and best
      chemotherapy regimen. An important randomized trial of concurrent vs. sequential
      chemoradiotherapy has been conducted in Japan, which has suggested that the
      concurrent schedule has survival benefit. Many trials of concurrent
      chemoradiotherapy with the new agents are currently performed or planned, but
      potential toxicity of the concurrent chemoradiotherapy must be carefully
      evaluated.

PMID- 9767616
TI  - Non-surgical therapy for patients with advanced non-small cell lung cancer.
AB  - Non-small cell lung cancer is the major cancer problem in the Western World.
      Treatment and prognosis are highly stage dependent, although overall only 5-10%
      of patients will be alive 5 years after diagnosis. Patients with early stage
      disease are treated with surgery alone. However, for patients with locally
      advanced disease there is increasing evidence that combined modality approaches,
      incorporating chemotherapy, radiotherapy and/or surgery result in modest
      improvements in survival. For patients with metastatic non-small cell lung cancer
      there is evidence from metaanalyses and randomised studies that chemotherapy
      results in improvements in both duration and quality of life. Despite these
      advances, there is substantial room for further improvement and therefore,
      wherever possible, patients should be enrolled in well designed clinical studies.

PMID- 9767617
TI  - Clinical efficacy of the FLUTTER device for airway mucus clearance in patients
      with diffuse panbronchiolitis.
AB  - Expectoration of mucus is important in preventing the development of airway
      inflammation in patients with diffuse panbronchiolitis (DPB). To evaluate the
      clinical efficacy of the FLUTTER device in clearing mucus from the airways of
      patients with DPB who have difficulty expectorating, we assessed pulmonary
      function and symptoms in patients treated with FLUTTER. Eight patients in a
      stable clinical condition with DPB were included in the study. The study was
      divided into two consecutive, 1-week periods. The initial week was an observation
      week. During the following week, patients used FLUTTER four times daily.
      Expectorated sputum was collected in a container and weighed every day during 2
      weeks. Pulmonary function, partial oxygen pressure and partial carbon dioxide
      pressure in arterial blood were measured in all patients on the last day of the
      observation week and the FLUTTER treatment week. A symptom score for difficulty
      of expectoration was determined by questionnaire. A pneumothorax developed in one
      patient during using FLUTTER. The mean daily sputum weight and peak expiratory
      flow rate increased significantly after treatment with FLUTTER ( P< 0.04 and P<
      0.02, respectively). Symptom score improved significantly after using FLUTTER (
      P< 0.02). We conclude that the use of FLUTTER is effective in clearing mucus from
      the airways. However, the development of a pneumothorax may complicate use of the
      procedure in some cases.

PMID- 9767618
TI  - Bronchiolitis obliterans organizing pneumonia in Korea.
AB  - An analysis of the clinical features in 23 cases of bronchiolitis obliterans
      organizing pneumonia (BOOP) in Korea is presented. Six were men and 17 were
      female, with a male-to-female ratio of 1:2.4. Idiopathic BOOP was present in 18
      of these patients, connective tissue disease-associated BOOP in five and all of
      them were females. The most frequent symptoms were dyspnoea and coughing in both
      groups; and crackles were the most prominent physical findings. Leukocytosis was
      observed in seven of the idiopathic BOOP group and all in the connective tissue
      disease-associated BOOP group. In most cases, FVC, FEV 1, diffusing capacity and
      arterial O2 pressure were reduced. In roentgenographic study, patchy air space
      consolidation was the major finding and subpleural predominance was observed in
      the majority of patients in both groups. Migration of lesions were identified in
      only two patients with idiopathic BOOP. Steroid treatment was effective in all of
      idiopathic BOOP. In contrast to previous reports, an analysis of the 23 Korean
      BOOP patients showed several interesting points. First, a female predominance was
      observed. Second, migration of lesion was rare. Third, it did not show any
      different prognosis in patients with reticular pattern on roentgenogram compared
      with patients with patchy air space consolidation on roentgenogram. Whether these
      differences were due to ethnic or environmental factors is to be determined.

PMID- 9767619
TI  - Increased use of inhaled corticosteroids and reduced hospitalizations in adult
      asthmatics: 11 years' experience in a Japanese hospital.
AB  - Until recently, inhaled corticosteroids have not been recognized as a first-line
      drug mainly because of the traditional polypharmaceutical approach to asthma in
      Japan. To examine the trend more precisely following the introduction of inhaled
      corticosteroids, we retrospectively analysed the relation between the number of
      prescriptions for anti-asthma drugs including inhaled corticosteroids and the
      number of hospitalizations due to asthma exacerbation, near fatal episodes and
      deaths from asthma for a period of 11 years from 1986 to 1996 at Kobe City
      General Hospital (KCGH). A marked decline in these actual indices in patients
      attending KCGH, which shows the improvement in asthma control, started
      coincidentally with the increased use of inhaled corticosteroid, which was
      followed by both a discontinuation of the trend for increased use of inhaled beta
      agonists and the decreased use of oral anti-asthma agents. There was no
      significant difference in the mean duration of hospital stays between 1988 and
      1996. Although the intensification of patient education is likely to play an
      important role in enhancing the protective effect of inhaled corticosteroids, we
      highly suspect that the major contributory factor in the great decline in
      hospitalizations is the increased use of inhaled corticosteroids.

PMID- 9767621
TI  - Correlation between clinical and pathological features of pulmonary thromboemboli
      and the development of infarcts.
AB  - Factors that predispose pulmonary thromboembolism to infarction have not been
      completely understood. The present autopsy study was carried out to evaluate
      these factors both clinically and pathologically. Between 36 subjects with
      pulmonary infarction and 33 individuals who had multiple pulmonary
      thromboembolism but no infarction, clinical and pathological features including
      congestive heart failure (CHF), shock, sepsis, neoplasm, emphysema, pneumonia,
      the amount of pleural effusion, diameter of occluded arteries, and segmental and
      dimensional location of thromboemboli were compared. Multiple regression analysis
      revealed that clinically CHF was significantly associated with the development of
      infarction. In pathological factors, thromboemboli located in the distal artery
      and in the lower lobe were significantly associated with infarction. The size of
      the infarcts was small and all the complete infarcts were in contact with the
      pleura. In addition to CHF, occlusion of small arteries in the lower lobe and
      near the pleura seems to be associated with the occurrence of infarction.

PMID- 9767622
TI  - CYFRA 21-1 and ProGRP, tumor markers of lung cancer, are elevated in chronic
      renal failure patients.
AB  - Serum levels of CYFRA 21-1(cytokeratin-19 fragment) and ProGRP (pro-gastrin
      releasing peptide), the new prognostic markers of lung cancer, were measured by
      ELISA (enzyme-linked immunoadsorbent assay) in 27 (for CYFRA 21-1; male 13,
      female 14; age 54+/-17 years) or 22 (for ProGRP; male 9, female 13; age 59+/-18
      years) patients with various serum creatinine levels, 42 haemodialysis (HD)
      patients (male 24, female 18; age 59+/-14 years) and 30 continuous ambulatory
      peritoneal dialysis (CAPD) patients (male 18, female 12; age 48+/-9 years). All
      the patients were without clinical and radiological signs of lung cancer.
      Positive correlations were found between serum creatinine and serum CYFRA 21-1
      and ProGRP levels. Serum levels of CYFRA 21-1 were above the cutoff limit (3.5
      ng/mL) in 57% of HD patients (mean 4.07+/-1.56 ng/mL) and in 73% of CAPD patients
      (mean 4.87+/-1.56 ng/mL). Serum levels of ProGRP were above the cutoff limit
      (46.0 pg/mL) in 90% of HD patients (mean 107.0+/-59.4 pg/mL) and in 93% of CAPD
      patients (mean 112.4+/-44.5 pg/mL). Our data indicate that evaluation of renal
      function is essential when the measurement of these tumor markers is to be
      applied as one of the diagnostic tools of lung cancer.

PMID- 9767624
TI  - Sarcoidosis in monozygotic twins.

PMID- 9767623
TI  - Marked elevation of CA19-9 in a patient with idiopathic pulmonary fibrosis: CA19
      9 as a bad prognostic factor.
AB  - A 53-year-old Japanese female, who had been suffering from idiopathic pulmonary
      fibrosis (IPF) for 3 years, was admitted with dyspnoea. The important laboratory
      finding on admission was a serum CA19-9 level of 649 U/mL. Despite steroid
      treatment for IPF, her respiratory condition gradually deteriorated with the
      increase of serum CA19-9 level up to 3020 U/mL and she died of respiratory
      failure. Immunohistochemistry showed the positive stain of CA19-9 in
      bronchoepithelial cells. We also reviewed the Index Medics and picked up the
      cases who had elevation of CA19-9 more than 1000 U/mL, and six patients were
      listed. Five of these six patients died within 6 months, therefore the marked
      elevation of CA19-9 seemed to be a bad prognostic factor in patients with
      pulmonary fibrosis.

PMID- 9767620
TI  - Comparative evaluation of sialylated carbohydrate antigens, KL-6, CA19-9 and SLX
      as serum markers for interstitial pneumonia.
AB  - We compared diagnostic values of three serum carbohydrate antigens, KL-6, CA19-9
      and SLX to discriminate interstitial pneumonia (IP) from alveolar pneumonia and
      healthy volunteers. Subjects consisted of 13 patients with idiopathic pulmonary
      fibrosis and 10 associated with collagen vascular diseases, 12 patients with
      sarcoidosis and 70 controls (52 healthy volunteers and 18 patients with alveolar
      pneumonia). Cut-off values were determined at the level at which the diagnostic
      accuracy became the highest for each marker, 449 U/mL for KL-6, 26 U/mL for CA19
      9 and 41 U/mL for SLX. The sensitivity, the specificity and the diagnostic
      accuracy were 74.3% (26/35), 98.6% (69/70) and 90.5% (95/105) in KL-6, 42.9%
      (15/35), 94.3% (66/70) and 77.1% (81/105) in CA19-9, and 20.0% (7/35) and 95.7%
      (67/70) and 70.5% (74/105) in SLX, respectively. Receiver operating
      characteristic curves revealed that KL-6 was far superior to both CA19-9 and SLX.
      These results suggest that KL-6 is the best marker for interstitial pneumonia
      among these carbohydrate antigens.

PMID- 9767625
TI  - Elevated soluble Fas levels in herpes zoster patients.

PMID- 9767626
TI  - Manual of nail disease and surgery 

PMID- 9767627
TI  - Bullous pemphigoid with circulating autoantibodies against the basal and apical
      lateral surfaces of the basal keratinocytes.

PMID- 9767628
TI  - Syntheses of trans-5-oxo-hexahydro-pyrrolo[3,2-b]pyrroles and trans-5-oxo
      hexahydro-furo[3,2-b]pyrroles (pyrrolidine trans-lactams and trans-lactones): new
      pharmacophores for elastase inhibition.

PMID- 9767629
TI  - Structure-based design of cathepsin K inhibitors containing a benzyloxy
      substituted benzoyl peptidomimetic.
AB  - Peptidomimetic cathepsin K inhibitors have been designed using binding models
      which were based on the X-ray crystal structure of an amino acid-based, active
      site-spanning inhibitor complexed with cathepsin K. These inhibitors, which
      contain a benzyloxybenzoyl group in place of a Cbz-leucine moiety, maintained
      good inhibitory potency relative to the amino acid-based inhibitor, and the
      binding models were found to be very predictive of relative inhibitor potency.
      The binding mode of one of the inhibitors was confirmed by X-ray crystallography,
      and the crystallographically determined structure is in close qualitative
      agreement with the initial binding model. These results strengthen the validity
      of a strategy involving iterative cycles of structure-based design, inhibitor
      synthesis and evaluation, and crystallographic structure determination for the
      discovery of peptidomimetic inhibitors.

PMID- 9767630
TI  - Investigations of neurotrophic inhibitors of FK506 binding protein via Monte
      Carlo simulations.
AB  - The binding and solution-phase properties of six inhibitors of FK506 binding
      protein (FKBP12) were investigated using free energy perturbation techniques in
      Monte Carlo statistical mechanics simulations. These nonimmunosuppressive
      molecules are of current interest for their neurotrophic activity when bound to
      FKBP12 as well as for their potential as building blocks for chemical inducers of
      protein dimerization. Relative binding affinities were computed and analyzed for
      ligands differing by a phenyl ring, an external phenyl or pyridyl substituent,
      and a pipecolyl or prolyl ring. Such results are, in general, valuable for
      inhibitor optimization and, in the present case, bring into question some of the
      previously reported binding data.

PMID- 9767631
TI  - N-[omega-(Tetralin-1-yl)alkyl] derivatives of 3,3-dimethylpiperidine are highly
      potent and selective sigma1 or sigma2 ligands.
AB  - Several 3, 3-dimethyl-N-[omega-(tetrahydronaphthalen-1-yl)alkyl]piperidine
      derivatives and some related compounds were prepared. Their affinities and sigma
      subtype selectivities were investigated by radioligand binding assays, labeling
      sigma1 receptors with [3H]-SKF 10047 and sigma2 receptors with [3H]-DTG. Many
      tested compounds bound sigma1 and/or sigma2 receptors with nanomolar or
      subnanomolar IC50 values. Compound (+)-22, (+)-3,3-dimethyl-1-[3-(5-methoxy
      1,2,3, 4-tetrahydronaphthalen-1-yl)-n-propyl]piperidine, was the most potent
      (IC50 = 0.089 nM) and selective sigma1 ligand (1340-fold), showing a 10-fold
      enantioselectivity. Compounds 29 (3, 3-dimethyl-1-[4-(6-methoxy-1,2,3, 4
      tetrahydronaphthalen-1-yl)-n-butyl]piperidine) and 31 (3, 3-dimethyl-1-[5-(1,2,3,
      4-tetrahydronaphthalen-1-yl)-n-pentyl]piperidine) were highly potent (IC50 =
      0.016 nM and IC50 = 0.008 nM, respectively) and highly selective sigma2 ligands
      (more than 100000-fold).

PMID- 9767632
TI  - Geometrically and conformationally restrained cinnamoyl compounds as inhibitors
      of HIV-1 integrase: synthesis, biological evaluation, and molecular modeling.
AB  - Various cinnammoyl-based structures were synthesized and tested in enzyme assays
      as inhibitors of the HIV-1 integrase (IN). The majority of compounds were
      designed as geometrically or conformationally constrained analogues of caffeic
      acid phenethyl ester (CAPE) and were characterized by a syn disposition of the
      carbonyl group with respect to the vinylic double bond. Since the cinnamoyl
      moiety present in flavones such as quercetin (inactive on HIV-1-infected cells)
      is frozen in an anti arrangement, it was hoped that fixing our compounds in a syn
      disposition could favor anti-HIV-1 activity in cell-based assays. Geometrical and
      conformational properties of the designed compounds were taken into account
      through analysis of X-ray structures available from the Cambridge Structural
      Database. The polyhydroxylated analogues were prepared by reacting 3,4
      bis(tetrahydropyran-2-yloxy)benzaldehyde with various compounds having active
      methylene groups such as 2-propanone, cyclopentanone, cyclohexanone, 1,3
      diacetylbenzene, 2, 4-dihydroxyacetophenone, 2,3-dihydro-1-indanone, 2,3-dihydro
      1, 3-indandione, and others. While active against both 3'-processing and strand
      transfer reactions, the new compounds, curcumin included, failed to inhibit the
      HIV-1 multiplication in acutely infected MT-4 cells. Nevertheless, they
      specifically inhibited the enzymatic reactions associated with IN, being totally
      inactive against other viral (HIV-1 reverse transcriptase) and cellular (RNA
      polymerase II) nucleic acid-processing enzymes. On the other hand, title
      compounds were endowed with remarkable antiproliferative activity, whose potency
      correlated neither with the presence of catechols (possible source of reactive
      quinones) nor with inhibition of topoisomerases. The SARs developed for our
      compounds led to novel findings concerning the molecular determinants of IN
      inhibitory activity within the class of cinnamoyl-based structures. We
      hypothesize that these compounds bind to IN featuring the cinnamoyl residue C=C
      C=O in a syn disposition, differently from flavone derivatives characterized by
      an anti arrangement about the same fragment. Certain inhibitors, lacking one of
      the two pharmacophoric catechol hydroxyls, retain moderate potency thanks to
      nonpharmacophoric fragments (i.e., a m-methoxy group in curcumin) which favorably
      interact with an "accessory" region of IN. This region is supposed to be located
      adjacent to the binding site accommodating the pharmacophoric dihydroxycinnamoyl
      moiety. Disruption of coplanarity in the inhibitor structure abolishes activity
      owing to poor shape complementarity with the target or an exceedingly high strain
      energy of the coplanar conformation.

PMID- 9767634
TI  - Structure-based design of beta-lactamase inhibitors. 2. Synthesis and evaluation
      of bridged sulfactams and oxamazins.
AB  - A series of bridged monocyclic beta-lactams activated by various groups on the
      beta-lactam nitrogen (X = OCH2CO2H, OSO3H) has been synthesized and evaluated.
      Among them, the bridged sulfactams (X = OSO3H) were found to be effective beta
      lactamase inhibitors. They inhibit both class A and class C beta-lactamases.

PMID- 9767633
TI  - Structure-based design of beta-lactamase inhibitors. 1. Synthesis and evaluation
      of bridged monobactams.
AB  - Bridged monobactams are novel, potent, mechanism-based inhibitors of class C beta
      lactamases, designed using X-ray crystal structures of the enzymes. They
      stabilize the acyl-enzyme intermediate by blocking access of water to the enzyme
      inhibitor ester bond. Bridged monobactams are selective class C beta-lactamase
      inhibitors, with half-inhibition constants as low as 10 nM, and are less
      effective against class A and class B enzymes (half-inhibition constants > 100
      microM) because of the different hydrolysis mechanisms in these classes of beta
      lactamases. The stability of the acyl-enzyme complexes formed with class C beta
      lactamases (half-lives up to 2 days were observed) enabled determination of their
      crystal structures. The conformation of the inhibitor moiety was close to that
      predicted by molecular modeling, confirming a simple reaction mechanism, unlike
      those of known beta-lactamase inhibitors such as clavulanic acid and penam
      sulfones, which involve secondary rearrangements. Synergy between the bridged
      monobactams and beta-lactamase-labile antibiotics could be observed when such
      combinations were tested against strains of Enterobacteriaceae that produce large
      amounts of class C beta-lactamases. The minimal inhibitory concentration of the
      antibiotic of more than 64 mg/L could be decreased to 0.25 mg/L in a 1:4
      combination with the inhibitor.

PMID- 9767635
TI  - Acetylcholinesterase inhibitors: synthesis and structure-activity relationships
      of omega-[N-methyl-N-(3-alkylcarbamoyloxyphenyl)- methyl]aminoalkoxyheteroaryl
      derivatives.
AB  - Acetylcholinesterase (AChE) inhibitors are one of the most actively investigated
      classes of compounds in the search for an effective treatment of Alzheimer's
      disease. This work describes the synthesis, AChE inhibitory activity, and
      structure-activity relationships of some compounds related to a recently
      discovered series of AChE inhibitors: the omega-[N-methyl-N-(3
      alkylcarbamoyloxyphenyl)methyl]aminoalkoxy xanthen-9-ones. The influence of
      structural variations on the inhibitory potency was carefully investigated by
      modifying different parts of the parent molecule, and a theoretical model of the
      binding of one representative compound to the enzyme was developed. The
      biological properties of the series were investigated in some detail by
      considering not only the activity on isolated enzyme but the selectivity with
      respect to butyrylcholinesterase (BuChE) and the in vitro inhibitory activity on
      rat cerebral cortex as well. Some of the newly synthesized derivatives, when
      tested on isolated and/or AChE-enriched rat brain cortex fraction, displayed a
      selective inhibitory activity and were more active than physostigmine. In
      particular, compound 13, an azaxanthone derivative, displayed the best rat cortex
      AChE inhibition (190-fold higher than physostigmine), as well as a high degree of
      enzyme selectivity (over 60-fold more selective for AChE than for BuChE). When
      tested in the isolated enzyme, compound 13 was less active, suggesting some
      differences either in drug availability/biotransformation or in the inhibitor
      sensitive residues of the enzyme when biologically positioned in rat brain
      membranes.

PMID- 9767636
TI  - A novel class of adenosine A3 receptor ligands. 1. 3-(2-Pyridinyl)isoquinoline
      derivatives.
AB  - A series of 3-(2-pyridinyl)isoquinoline derivatives was synthesized as potential
      antagonists for the human adenosine A3 receptor by substitution of the 1
      position. The compounds were obtained by various synthetic routes from 1-amino-3
      (2-pyridinyl)isoquinoline. The affinity was determined in radioligand binding
      assays for rat brain A1 and A2A receptors and for the cloned human A3 receptor. A
      structure-activity relationship analysis indicated that a phenyl group when
      coupled by a spacer allowing conjugation on position 1 of the isoquinoline ring
      increased the adenosine A3 receptor affinity. In contrast, such a phenyl group
      directly bound to position 1 of the isoquinoline ring decreased affinity. Since
      the combination of a phenyl group together with a spacer raised adenosine A3
      receptor affinity, various spacers were investigated. VUF8501 (N-[3-(2
      pyridinyl)isoquinolin-1-yl]benzamidine (15) showed an affinity at the human
      adenosine A3 receptor of 740 nM. Substituent effects on the phenyl group were
      investigated by in vitro evaluation of a series of substituted benzamidines.
      Electron-donating groups at the para position of the benzamidine ring increased
      adenosine A3 receptor affinity. These investigations led to VUF8505 (4-methoxy-N
      [3-(2-pyridinyl)isoquinolin-1-yl]benzamidine(22)), which is a moderately potent
      and selective ligand for the human adenosine A3 receptor with an affinity of 310
      nM in our test system having negligible affinity for rat A1 and A2A receptors.

PMID- 9767637
TI  - A novel class of adenosine A3 receptor ligands. 2. Structure affinity profile of
      a series of isoquinoline and quinazoline compounds.
AB  - 1-Substituted 3-(2-pyridinyl)isoquinolines have been shown to form a novel class
      of adenosine A3 receptor ligands. In the present study further investigations of
      this new lead and the structure affinity relationships of this class of compounds
      are described. First, the influence of an amide group at position 1 of the
      isoquinoline ring on the adenosine A3 receptor affinity was determined. A
      carboxamide proved to be a useful spacer between the isoquinoline and a phenyl
      ring. N-[2-(2-pyridinyl)isoquinolin-4-yl]benzamide (VUF8507, compound 6) had an
      affinity of 200 nM at the adenosine A3 receptor. Second, we investigated the
      effects of substitution of the benzamide ring of 6 with a series of mono- and
      disubstituted N-[3-(2-pyridinyl)isoquinoline]benzamides. The ratio of the
      tautomers of the benzamides was determined in the solid state and in solution by
      spectroscopic techniques (IR and NMR). Affinities were determined in radioligand
      binding assays at rat brain A1 and A2A receptors and at cloned human A3 receptor.
      The benzamides showed higher adenosine A3 receptor affinity than aliphatic
      amides. We propose that the adenosine A3 receptor affinity of the different
      benzamides is related to their presence in either the iminol or amide form.
      Ligands present in the iminol form showed relatively high adenosine A3 receptor
      affinity. Finally, we explored the influence of replacement of C4 of the
      isoquinoline ring by a nitrogen atom. Comparison of isoquinolines with the
      corresponding quinazolines revealed that both compounds showed similar adenosine
      A3 receptor affinity. These investigations led to potent and selective human
      adenosine A3 receptor ligands with affinities in the nanomolar range. The subtype
      selective compound 4-methoxy-N-[2-(2-pyridinyl)quinazolin-4-yl]benzamide
      (VUF8504, 13) with an affinity of 17.0 nM at the human adenosine A3 receptor
      might become a useful tool in the pharmacological characterization or the
      investigation of the physiological function of this receptor.

PMID- 9767638
TI  - Substituted 4-acylpyrazoles and 4-acylpyrazolones: synthesis and multidrug
      resistance-modulating activity.
AB  - A series of 4-acyl-3-pyrazolone derivatives with a 3-substituted 2-hydroxy-3
      aminopropyl chain attached to pyrazole N-1 (7-20) as well as isomeric 4-acyl-5-(3
      substituted 3-amino-2-hydroxypropoxy)pyrazole derivatives (5, 6) were
      synthesized, and their multidrug resistance (MDR)-modulating activity was
      measured using the daunomycin efflux assay. Reaction of N1-substituted 4-acyl-3
      pyrazolones (tautomer to 4-acyl-5-hydroxypyrazoles) with excessive
      epichlorohydrin and successive treatment with an appropriate amine resulted in N
      alkylation and thus afforded the target pyrazolone derivatives 7-20. In contrast,
      O-alkylation occurred upon reaction with 1 equiv of epichlorohydrin and
      subsequent treatment with amine leading to the corresponding 4-acyl-5-pyrazolyl
      ethers 5 and 6. QSAR studies showed a good correlation of MDR-modulating activity
      with lipophilicity of the compounds. Inclusion of hydrogen bond acceptor strength
      and steric parameters as descriptors led to a QSAR equation with remarkably
      increased predictive power (r2cv = 0.92). Additionally, ortho substitution of the
      propanolamine side chain and the acyl moiety is favorable. Detailed NMR
      spectroscopic investigations were carried out with the title compounds.

PMID- 9767639
TI  - 4-(beta-Arylvinyl)-3-(beta-arylvinylketo)-1-ethyl-4-piperidinols and related
      compounds: a novel class of cytotoxic and anticancer agents.
AB  - The syntheses of a series of 1-aryl-5-diethylamino-1-penten-3-one hydrochlorides
      1 and 1-aryl-3-diethylamino-1-propanone hydrochlorides 4 were accomplished.
      Attempts to prepare the corresponding bis(5-aryl-3-oxo-4-pentenyl)ethylamine
      hydrochlorides 2 and bis(3-aryl-3-oxopropyl)ethylamine hydrochlorides 5 led to
      the formation of a series of 4-(beta-arylvinyl)-3-(beta-arylvinylketo)-1-ethyl-4
      piperidi nol hydrochlorides 9 and 4-aryl-3-arylketo-1-ethyl-4-piperidinol
      hydrochlorides 11, most of which were converted subsequently into the
      corresponding quaternary ammonium salts 10 and 12, respectively. The structures
      of these compounds were determined by 1H NMR spectroscopy and confirmed by X-ray
      crystallography of representative molecules. Most compounds displayed significant
      cytotoxicity toward murine P388 and L1210 cells as well as human tumors. In
      general, Mannich bases containing olefinic bonds were more cytotoxic than the
      analogues without this functional group, while the piperidines 9 and 11 were more
      potent than the acyclic analogues 1 and 4, respectively. Correlations were noted
      between various physicochemical constants in the aryl rings and cytotoxicity.
      Compound 9d displayed promising in vivo activity against colon cancers. This
      study has revealed that the piperidines 9 and 11 constitute new classses of
      cytotoxic agents.

PMID- 9767640
TI  - Design, synthesis, and biological activities of new thieno[3,2-d] pyrimidines as
      selective type 4 phosphodiesterase inhibitors.
AB  - A common pharmacophore for compounds structurally related to nitraquazone has
      been derived. Using this pharmacophore, new structures have been designed,
      synthesized, and evaluated for their inhibitory potencies against cyclic
      adenosine 5'-monophosphate (cAMP) specific phosphodiesterase (PDE 4). From these
      compounds, 4-benzylamino-2-butylthieno[3,2-d]pyrimidine (4) was selected for
      optimization. The effects of changes to the lipophilic groups and the amino
      linkage on the PDE 4 activity have been investigated. As a result, some potent
      PDE 4 inhibitors, selective with respect to PDE 3, have been identified. A
      selected group of compounds have been further evaluated for their ability to
      displace [3H]rolipram from its binding site and also to potentiate isoprenaline
      induced cAMP accumulation in isolated guinea pig eosinophils. Of these, 2-butyl-4
      cyclohexylaminothieno[3,2-d]pyrimidine (33) has an interesting profile, with an
      important improvement in PDE 4/[3H]rolipram ratio with respect to reference
      drugs, and good activity in cAMP potentiation, consistent with efficient cell
      penetration.

PMID- 9767641
TI  - New platelet fibrinogen receptor glycoprotein IIb-IIIa antagonists: orally active
      series of N-alkylated amidines with a 6,6-bicyclic template.
AB  - The design, synthesis, and pharmacological evaluation of (S)-(-)-ethyl [6-[4
      (morpholinoformimidoyl)benzamido]-3, 4-dihydro-2H-1-benzopyran-3-yl]acetate
      hydrochloride ((S)-4.HCl, MS-180), an orally active glycoprotein IIb-IIIa (GPIIb
      IIIa) antagonist, are reported. Pharmacophore mapping of amidino and carboxyl
      groups of already known GPIIb-IIIa antagonists led to the synthesis of nine
      amidino acids containing 6,6-bicyclic ring skeletons (10a-i). Among them, the
      compounds 10a,c,e having an amide bond and 1,2,3,4-tetrahydronaphthalene or 3, 4
      dihydro-2H-1-benzopyran skeleton showed marked inhibitions with IC50 values of 46
      57 nM in human platelet aggregation assay in vitro, but low oral activities. N
      Alkylation of the amidino group coupled with the ester prodrug approach afforded
      MS-180 ((S)-4.HCl), which generates in vivo the corresponding carboxylic acid (S)
      3 as an active species. In vitro, (S)-3 inhibited ADP-induced aggregation of
      guinea pig, dog, and human platelets (IC50 = 110, 253, and 35 nM, respectively)
      and inhibited the binding of fibrinogen to immobilized GPIIb-IIIa of human
      platelets (IC50 = 0.12 nM). After oral administration of MS-180 ((S)-4.HCl) to
      fasted beagle dog, ex vivo inhibition of platelet aggregation was observed. The
      maximal inhibitions were observed 2-4 h after dosing with dose dependency (60%
      inhibition at a dose of 1 mg/kg, 85% at 3 mg/kg, and 100% at 10 mg/kg,
      respectively) and the extent of the inhibitions paralleled the plasma
      concentration of the active species (S)-3. On the basis of these studies, we
      selected MS-180 ((S)-4.HCl) as a candidate for clinical evaluation as a drug for
      the treatment and prevention of thrombosis in patients.

PMID- 9767642
TI  - A novel class of orally active non-peptide bradykinin B2 receptor antagonists. 2.
      Overcoming the species difference between guinea pig and man.
AB  - Recently we reported the identification of a series of 8-[[3-(N-acylglycyl-N
      methylamino)-2, 6-dichlorobenzyl]oxy]-3-halo-2-methylimidazo[1,2-a]pyridines as
      the first orally active non-peptide bradykinin (BK) B2 receptor antagonists (1
      3). These compounds inhibited the specific binding of [3H]BK to guinea pig ileum
      membrane preparations expressing B2 receptors with nanomolar IC50's and also
      displayed in vivo functional antagonistic activities against BK-induced
      bronchoconstriction in guinea pigs at 1 mg/kg by oral administration. However, it
      was found that their affinities for the B2 receptors in human A-431 cells (human
      epidermoid carcinoma) were much lower. Intensive modifications of the terminal
      substituents at the glycine moiety elucidated the structure-activity
      relationships (SAR) for human B2 receptors, leading to an extended basic
      framework which incorporated a novel key pharmacophore. Thus, we overcame the
      species difference and identified the first clinical candidate 18c (FR167344)
      with IC50's of 0.66 and 1.4 nM for guinea pig ileum and human A-431 cells,
      respectively. This compound displayed in vivo functional antagonistic activity
      against BK-induced bronchoconstriction in guinea pigs with an ED50 value of 0.17
      mg/kg by oral administration. This novel non-peptide B2 antagonist is extremely
      potent both in vitro and in vivo by oral administration and is expected to be the
      first member of a new class of drug for the treatment of various inflammatory
      diseases.

PMID- 9767643
TI  - A novel class of orally active non-peptide bradykinin B2 receptor antagonists. 3.
      Discovering bioisosteres of the imidazo[1,2-a] pyridine moiety.
AB  - Recently we reported on overcoming the species difference of our first orally
      active non-peptide bradykinin (BK) B2 receptor antagonists, incorporating an 8
      [[3-(N-acylglycyl-N-methylamino)-2, 6-dichlorobenzyl]oxy]-3-halo-2
      methylimidazo[1,2-a]pyridine skeleton, leading to identification of the first
      clinical candidate 4a (FR167344). With this potent new lead compound in hand, we
      then investigated further refinement of the basic framework by replacement of the
      imidazo[1,2-a]pyridine moiety and discovered several bioisosteric heterocycles.
      Extensive optimization of these new heteroaromatic derivatives revealed the
      detailed structure-activity relationships (SAR) around the imidazo[1, 2
      a]pyridine ring and the 2,6-dichlorobenzyl moiety, leading to the discovery of
      our second clinical candidate 87b (FR173657) which inhibited the specific binding
      of [3H]BK to recombinant human B2 receptors expressed in Chinese hamster ovary
      (CHO) cells and guinea pig ileum membrane preparations expressing B2 receptors
      with IC50's of 1.4 and 0.46 nM, respectively. This compound also displayed
      excellent in vivo functional antagonistic activity against BK-induced
      bronchoconstriction in guinea pigs with an ED50 value of 0.075 mg/kg by oral
      administration. Further modifications of the terminal substituents on the
      pyridine moiety led to a novel pharmacophore and resulted in the identification
      of 99 (FR184280), whose IC50 value for human B2 receptors (0.51 nM) was
      comparable to that of the second-generation peptide B2 antagonist Icatibant.

PMID- 9767644
TI  - Synthesis and antibacterial activity of ketolides (6-O-methyl-3-oxoerythromycin
      derivatives): a new class of antibacterials highly potent against macrolide
      resistant and -susceptible respiratory pathogens.
AB  - In the search for new antibiotics active against macrolide-resistant pneumococci
      and Haemophilus influenzae, we synthesized a new class of 3-oxo-6-O
      methylerythromycin derivatives, so-called "ketolides". A keto function was
      introduced in position 3 after removal of L-cladinose, a sugar which has long
      been thought essential. Further modifications of the macrolactone backbone
      allowed us to obtain three different series of 9-oxime, 11,12-carbamate, and 11,
      12-hydrazonocarbamate ketolides. These compounds were found to be very active
      against penicillin/erythromycin-resistant pneumococci and noninducers of MLSB
      resistance. The 11,12-substituted ketolide 61 (HMR 3004) demonstrated a potent
      activity against multiresistant pneumococci associated with a well-balanced
      activity against all bacteria involved in respiratory infections including H.
      influenzae, Mycoplasma catarrhalis, group A streptococci, and atypical bacteria.
      In addition HMR 3004 displayed high therapeutic activity in animals infected by
      all major strains, irrespective of their resistance phenotype.

PMID- 9767645
TI  - Synthesis and antimalarial activities of fluoroalkyl derivatives of
      dihydroartemisinin.
AB  - Fluoroalkyl ethers (4) of dihydroartemisinin (2) have been prepared by reaction
      of fluoroalkyl alcohols with dihydroartemisinin by different methods (BF3,Et2O or
      TMSCl catalysis or Mitsunobu reaction). Ethers 4a-d derived from primary
      fluoroalkyl alcohols were obtained in moderate to good yields by these methods.
      Ethers 4e-j have been prepared from fluoroalkyl secondary and tertiary alcohols
      and phenol using the Mitsunobu reaction. Although in vitro antimalarial
      activities of ethers toward Plasmodium falciparum W-2 asiatic strain are
      moderate, in vivo activities against Plasmodium berghei (NT 173) are excellent.

PMID- 9767646
TI  - Novel 1,1,3-trioxo-2H,4H-thieno[3,4-e][1,2,4]thiadiazine derivatives as non
      nucleoside reverse transcriptase inhibitors that inhibit human immunodeficiency
      virus type 1 replication.
AB  - The 1,1,3-trioxo-2H,4H-thieno[3,4-e][1,2,4]thiadiazines (TTDs) represent a
      recently discovered chemical class of non-nucleoside reverse transcriptase
      inhibitors that selectively block human immunodeficiency virus type 1
      replication. In a search for a better understanding of their mode of binding and
      with the aim of obtaining novel lead compounds, a second series of TTD
      derivatives was synthesized and evaluated for antiviral activity. The design of
      the new compounds was based on a variety of chemical modifications which were
      carried out in the original prototype 20a (QM 96521). Substitution of a halogen
      at the meta position of the N-2 benzyl group resulted in an improvement of the
      antiviral activity by 1 order of magnitude. Compounds bearing at the N-4 position
      a cyanomethyl, propargyl, or benzyl substituent were found to be the most potent
      of the series. Modifying the thieno[3,4-e] ring fused to the 1,2,4-thiadiazine
      moiety to other heterocyclic ring systems decreased the potency. The results
      obtained in this investigation have provided new indications for the design of
      even more effective TTDs.

PMID- 9767647
TI  - Novel, highly potent aldose reductase inhibitors: (R)-(-)-2-(4-bromo-2
      fluorobenzyl)-1,2,3,4- tetrahydropyrrolo[1,2-a]pyrazine -4-spiro-3'-pyrrolidine
      1,2',3,5'-tetrone (AS-3201) and its congeners.
AB  - A series of novel tetrahydropyrrolo[1,2-a]pyrazine derivatives were synthesized
      and evaluated as aldose reductase inhibitors (ARIs) on the basis of their
      abilities to inhibit porcine lens aldose reductase (AR) in vitro and to inhibit
      sorbitol accumulation in the sciatic nerve of streptozotocin-induced diabetic
      rats in vivo. Of these compounds, spirosuccinimide-fused tetrahydropyrrolo[1, 2
      a]pyrazine-1,3-dione derivatives showed significantly potent AR inhibitory
      activity. In the in vivo activity of these derivatives, 2-(4-bromo-2
      fluorobenzyl)-1,2,3,4-tetrahydropyrrolo[1, 2-a]pyrazine-4-spiro-3'-pyrrolidine
      1,2',3,5'-tetrone (23t) (SX-3030) showed the best oral activity. The enantiomers
      of 23t were synthesized, and the biological activities were evaluated. It was
      found that AR inhibitory activity resides in the (-)-enantiomer 43 (AS-3201),
      which was 10 times more potent in inhibition of the AR (IC50 = 1.5 x 10(-8) M)
      and 500 times more potent in the in vivo activity (ED50 = 0.18 mg/kg/day for 5
      days) than the corresponding (+)-enantiomer 44 (SX-3202). From these results, AS
      3201 was selected as the candidate for clinical development. The absolute
      configuration of AS-3201 was also established to be (R)-form by single-crystal X
      ray analysis. In this article we report the preparation and structure-activity
      relationship (SAR) of tetrahydropyrrolopyrazine derivatives including a novel
      ARI, AS-3201.

PMID- 9767648
TI  - Predictive models for GABAA/benzodiazepine receptor subtypes: studies of
      quantitative structure-activity relationships for imidazobenzodiazepines at five
      recombinant GABAA/benzodiazepine receptor subtypes [alphaxbeta3gamma2 (x = 1-3,
      5, and 6)] via comparative molecular field analysis.
AB  - Affinities of a series of substituted imidazobenzodiazepines at recombinant
      alpha1beta3gamma2, alpha2beta3gamma2, alpha3beta3gamma2, alpha5beta3gamma2, and
      alpha6beta3gamma2 GABAA/benzodiazepine receptor subtypes are reported. Many of
      these ligands displayed high affinities (low-nanomolar to subnanomolar scale) at
      all five receptor subtypes. Furthermore, a number of imidazobenzodiazepines
      exhibited relatively good selectivity at the alpha5-containing receptor isoform.
      For example, ligand 27 (RY-023) demonstrated a 55-fold higher selectivity at
      alpha5beta3gamma2 isoforms in comparison to other receptor subtypes. The affinity
      ratio of alpha1 (the most prevalent subtype in the brain) to alpha5 of this
      series of ligands ranged from 60- to 75-fold for the most selective ligands.
      Studies of quantitative structure-activity relationships (QSAR) by means of
      comparative molecular field analysis (CoMFA) were carried out. As a result,
      examination of CoMFA models for all five receptor subtypes demonstrated their
      predictability for affinities of imidazobenzodiazepines at the five receptor
      subtypes. Regions of molecular fields which would favor or disfavor the binding
      affinity of a ligand at a specific receptor subtype were examined via CoMFA for
      alpha1, alpha2, alpha3, alpha5, and alpha6 subtypes. A CoMFA regression analysis
      was applied to predict the ratio of Ki alpha1/Ki alpha5, an index for the
      selectivity of a ligand at the alpha5 subtype. All of the CoMFA models offered
      good cross-validated correlations for the ligands in the test set as well as the
      ratios of Ki alpha1/Ki alpha5, which demonstrated their potential for prediction.

PMID- 9767649
TI  - N-Substituted 9beta-methyl-5-(3-hydroxyphenyl)morphans are opioid receptor pure
      antagonists.
AB  - The inhibition of radioligand binding and [35S]GTPgammaS functional assay data
      for N-methyl- and N-phenethyl-9beta-methyl-5-(3-hydroxyphenyl)morphans (5b and
      5c) show that these compounds are pure antagonists at the micro, delta, and kappa
      opioid receptors. Since 5b and 5c have the 5-(3-hydroxyphenyl) group locked in a
      conformation comparable to an equatorial group of a piperidine chair
      conformation, this information provides very strong evidence that opioid
      antagonists can interact with opioid receptors in this conformation. In addition,
      it suggests that the trans-3, 4-dimethyl-4-(3-hydroxyphenyl)piperidine class of
      antagonist operates via a phenyl equatorial piperidine chair conformation.
      Importantly, the close relationship between the 4-(3-hydroxyphenyl)piperidines
      and 5-(3-hydroxyphenyl)morphan antagonists shows that the latter class of
      compound provides a rigid platform on which to build a novel series of opioid
      antagonists.

PMID- 9767650
TI  - Universal template approach to drug design: polyamines as selective muscarinic
      receptor antagonists.
AB  - The concept that polyamines may represent a universal template in the receptor
      recognition process is embodied in the design of new selective muscarinic
      ligands. Tetraamines 4-7 and 16-20 and diamine diamides 8-15 were synthesized,
      and their pharmacological profiles at muscarinic receptor subtypes were assessed
      by functional experiments in isolated guinea pig left atrium (M2) and ileum (M3)
      and by binding assays in rat cortex (M1), heart (M2), submaxillary gland (M3),
      and NG 108-15 cells (M4). It has been confirmed that appropriate substituents on
      the terminal nitrogens of a tetraamine template can tune both affinity and
      selectivity for muscarinic receptors. The novel tetraamine C-tripitramine (17)
      was able to discriminate significantly M1 and M2 receptors versus the other
      subtypes, and in addition it was 100-fold more lipophilic than the lead compound
      tripitramine. Compound 14 (tripinamide), in which the tetraamine backbone was
      transformed into a diamine diamide one, retained high affinity for muscarinic
      subtypes, displaying a binding affinity profile (M2 > M1 > M4 > M3) qualitatively
      similar to that of tripitramine. Both these ligands, owing to their improved
      lipophilicity relative to tripitramine and methoctramine, could serve as tools in
      investigating cholinergic functions in the central nervous system. Furthermore,
      notwithstanding the fact that the highest affinity was always associated with
      muscarinic M2 receptors, for the first time polyamines were shown to display high
      pA2 values also toward muscarinic M3 receptors.

PMID- 9767651
TI  - Halogenated chalcones with high-affinity binding to P-glycoprotein: potential
      modulators of multidrug resistance.
AB  - Previous studies have shown that flavonoids are modulators of the transmembrane P
      glycoprotein (P-gp) which mediates cell multidrug resistance. Some structural
      elements have been identified which seem to contribute to these compounds'
      activity. In the present study, a series of halogenated chalcones was prepared to
      further explore the structural requirements for the P-gp modulation. Four
      halogenated chalcones have been synthesized and evaluated as potential modulators
      of P-gp-mediated multidrug resistance of cancer cells by in vitro assays using a
      purified recombinant domain of the transporter containing the modulator binding
      site. Halogenated chalcones exhibited high-affinity binding, the 2',4', 6'
      trihydroxy-4-iodochalcone behaving as the most potent compound with a KD value in
      the nanomolar range.

PMID- 9767652
TI  - N-(Iodopropenyl)-octahydrobenzo[f]- and -[g]quinolines: synthesis and adrenergic
      and dopaminergic activity studies.
AB  - A series of N-(iodopropenyl)-octahydrobenzo[f]- and -[g]quinolines was
      synthesized and assayed in vitro for their dopaminergic and alpha-adrenergic
      activity. Structure-activity relationship (SAR) analysis revealed that the tested
      benzoquinolines exhibited activity at the D1 rather than the D2 receptor sites in
      contrast to the D2 receptor subfamily activity reported for their aminotetralin
      congeners. N-Iodopropenyl substitution was apparently a decisive factor for D1
      activity independent of ring substitution pattern. Considering the structural
      factors influencing alpha-adrenergic activity, in a general trend, N-iodopropenyl
      analogues were alpha1-active, with the ring-hydroxylated congeners exhibiting the
      highest affinity. Affinity to the alpha2 receptor was even higher with no
      detectable trend of SAR. However, a combination of the linear arrangement of the
      [g]-ring system, combined with the ring hydroxyl and the N-iodopropenyl
      substitution in compound 5c, resulted in a significant enhancement of alpha2
      activity in this series as demonstrated by an IC50 value of 0.5 nM. A new
      synthetic approach to the [g]benzoquinoline system is also described.

PMID- 9767653
TI  - 4-Alkynylphenyl imidazolylpropyl ethers as selective histamine H3-receptor
      antagonists with high oral central nervous system activity.
AB  - In search for potent and therapeutically useful H3-receptor antagonists, we
      prepared novel 4-alkynylphenyl ether derivatives of 3-(1H-imidazol-4-yl)propanol
      in a convenient synthetic route. All compounds were tested for in vitro and in
      vivo H3-receptor antagonist activity as well as for H3-receptor selectivity
      versus H1- and H2-receptors. The presented 4-alkynylphenyl ethers are highly
      potent and selective H3 antagonists showing oral activity and improved brain
      penetration. Particularly 4-ethynylphenyl 3-(1H-imidazol-4-yl)propyl ether (14a)
      displays striking in vitro and in vivo activity with a -log Ki value of 8.6 and
      an ED50 value of 0.12 mg/kg. At present 14a is the most potent H3-receptor
      antagonist in vivo and may therefore be a potential drug for the therapy of H3
      receptor-dependent diseases of the central nervous system (CNS).

PMID- 9767654
TI  - 7-Arylidenenaltrexones as selective delta1 opioid receptor antagonists.
AB  - A series of 7-arylidinenaltrexones (2a-m) related to the prototypical delta1
      selective antagonist, 7-benzylidenenaltrexone 1 (BNTX), have been synthesized in
      an effort to develop more selective ligands. Testing in smooth muscle
      preparations revealed that members of the series exhibited varying degrees of
      selectively for delta receptors, with the o-methoxy (2e) and o-chloro (2j)
      congeners being most potent and most selective (Ke approximately 0.8 nm).
      Evaluation of 1, 2e, and 2f sc in mice using the tail-flick procedure indicated
      that they are selective delta1 opioid receptor antagonists in the lower dose
      range. At high doses these ligands, including BNTX, exhibited decreased delta1
      selectivity due to increases in the ED50 ratios of [D-Ser2,Leu5]enkephalin-Thr6
      and morphine. It is concluded that 2e and 2f possess in vivo selectivity similar
      to that of BNTX, but are less potent as delta1 antagonists.

PMID- 9767656
TI  - In Situ Electron Microscopy: Introduction.

PMID- 9767655
TI  - From the Editor.

PMID- 9767657
TI  - Focused Ion Beam Interfaced with a 200 keV Transmission Electron Microscope for
      In Situ Micropatterning on Semiconductors.
AB  - : A focused ion beam (FIB) interface attached to a column of 200 keV transmission
      electron microscope (TEM) was developed for in situ micropatterning to
      semiconductors. TEM specimens of Si and GaAs, and those of a thin Ni2Si layer on
      a Si substrate were micromilled in the TEM during observation. A set of 6 x 6-um
      squares and alphabet letters were patterned with a 25 keV Ga+-FIB of 0.2-um beam
      diameter at room temperature. The effect of FIB irradiation on the structural
      evolution was observed simultaneously by a TV-rate video camera and sequentially
      by regular film. FIB micropatterning to semiconductor specimens caused
      amorphization and Ga injection. The excess Ga in the specimens precipitated as
      metastable solid gamma-phase for Si and as liquid phase for GaAs. Ni2Si/Si
      specimens lost silicide crystallinity after FIB patterning. Annealing of these
      bilayer specimens at 673K resulted in the precipitation of Ni-rich silicide.

PMID- 9767658
TI  - Time-Resolved High-Resolution Transmission Electron Microscopy Using a Piezo
      Driving Specimen Holder for Atomic-Scale Mechanical Interaction.
AB  - : Time-resolved high-resolution transmission electron microscopy at a spatial
      resolution of 0.2 nm and a time resolution of 1/60 sec using a piezo-driving
      specimen holder is reported here. Various types of atomic processes in mechanical
      interaction, such as contact, bonding, deformation, and fracture, in nanometer
      sized gold crystallites and carbon nanotubes are demonstrated.

PMID- 9767659
TI  - High-Temperature In Situ Straining Experiments in the High-Voltage Electron
      Microscope.
AB  - : Design rules are described here for high-temperature straining stages for
      transmission electron microscopy. Temperatures above 1000 degreesC can be
      attained by electron bombardment of the specimen grips. Thermal equilibrium can
      be reached in a short time by carrying off the heat by water cooling. Some
      applications of this stage are described. Ferroelastic deformation was observed
      at 1150 degreesC in t' and partially stabilized zirconia, which changes the
      microstructure for successive dislocation plasticity. In the oxide-dispersion
      strengthened alloy INCOLOY MA 956, dislocations are impeded by oxide particles
      and move smoothly between the particles. At high temperatures, both the resting
      and traveling times control the average dislocation velocity. In MoSi2 single
      crystals of a soft orientation, dislocations with 1/2<111> Burgers vectors are
      created in localized sources and move on {110} planes in a viscous manner. The
      dislocations in Al-Pd-Mn single quasicrystals are oriented in preferred
      crystallographic directions and move in a viscous way as well. On the basis of in
      situ observations, conclusions are drawn for interpreting macroscopic deformation
      behavior at high temperatures.

PMID- 9767660
TI  - Understanding Interphase Boundary Dynamics by In Situ High-Resolution and Energy
      Filtering Transmission Electron Microscopy and Real-Time Image Simulation.
AB  - : This study discusses the use of in situ high-resolution transmission electron
      microscropy (HRTEM) techniques to determine the structure, composition, and
      interphase boundary dynamics during phase transformations at the atomic level.
      Three main in situ HRTEM techniques are described: (1) in situ HRTEM dynamic
      studies that are performed on the same precipitate plates from different viewing
      directions to determine the three-dimensional structure of the interfaces; (2) in
      situ compositional mapping of precipitate interfaces obtained by energy-filtering
      TEM experiments at temperature in a HRTEM, and (3) real-time HRTEM image
      simulations that are being created for comparison with and interpretation of
      experimental in situ HRTEM dynamic observations. The results from these studies
      demonstrate that it is possible to understand the mechanisms and kinetics of
      interphase boundary motion at the atomic level.

PMID- 9767661
TI  - Techniques for Studying Nanoparticle Sintering by Plan-View In Situ Transmission
      Electron Microscopy.
AB  - : We discuss various techniques for the characterization of supported
      nanoparticles by in situ plan-view transmission electron microscopy. In
      particular, we discuss here mechanisms of image contrast formation by particles
      undergoing reorientation on the surface of a single crystal substrate. We
      consider reorientation by a variety of mechanisms including rotation, sintering
      and grain growth, and surface diffusion. Experimental observations are presented
      and the data compared with theoretical predictions.

PMID- 9767663
TI  - In Situ Transmission Electron Microscope Observation of Melting of Aluminum
      Particles.
AB  - ; The processes of melting and freezing of aluminum (Al) particles have been
      observed directly in a transmission electron microscope. The liquid phase
      nucleated preferentially at the surface of an Al particle, surrounding the
      crystalline solid at the onset of melting. The liquid phase then propagated
      inside the Al particle at the expense of the solid.

PMID- 9767662
TI  - Ostwald Ripening of Self-Assembled Germanium Islands on Silicon(100).
AB  - : We describe here real-time, in situ observations of the formation of nanosize
      germanium (Ge) islands on silicon (Si). The deposition of Ge onto electron
      transparent Si(100) takes place in a UHV transmission electron microscope that
      has been modified to allow chemical vapor deposition to be carried out in the
      polepiece. We recorded the growth process at video rate and were therefore able
      to follow the evolution of individual islands. As the islands grew, we observed a
      coarsening process similar to classical Ostwald ripening, but which leads at
      certain times to a bimodal distribution of island sizes. We show that this
      phenomenon can be understood using a model in which a conventional coarsening
      process is modified by a transition between two different island shapes.

PMID- 9767664
TI  - In Situ High-Temperature Transmission Electron Microscopy Observations of the
      Formation of Nanocrystalline TiC from Nanocrystalline Anatase (TiO2).
AB  - : In this work, the high-temperature behavior of nanocrystalline TiO2 is studied
      using in situ transmission electron microscopy (TEM). These nanoparticles are
      made using wet chemical techniques that generate the anatase phase of TiO2 with
      average grain sizes of 6 nm. X-ray diffraction studies of nanophase TiO2 indicate
      the material undergoes a solid-solid phase transformation to the stable rutile
      phase between 600 degrees and 900 degreesC. This phase transition is not observed
      in the TEM samples, which remain anatase up to temperatures as high as 1000
      degreesC. Above 1000 degreesC, nanoparticles become mobile on the amorphous
      carbon grid and by 1300 degreesC, all anatase diffraction is lost and larger (50
      nm) single crystals of a new phase are present. This new phase is identified as
      TiC both from high-resolution electron microscopy after heat treatment and
      electron diffraction collected during in situ heating experiments. Video images
      of the particle motion in situ show the nanoparticles diffusing and interacting
      with the underlying grid material as the reaction from TiO2 to TiC proceeds.

PMID- 9767665
TI  - Oxidation and Reduction of Small Palladium Particles on Silica.
AB  - : We have used the technique of in situ electron microscopy to study the
      oxidation and reduction of the palladium (Pd) catalysts. In this study, we have
      subjected a Pd catalyst to oxidation and reduction cycles and studied the changes
      in particle structure and morphology with in situ electron diffraction and
      imaging. The PdO particles can be reduced to Pd metal in situ at temperatures as
      low as 200 degreesC in an atmosphere of a few Torr of both H2 and O2. We also
      found that essentially the same reduction occurred in the vacuums of 10(-6) to
      10(-7) Torr in two different electron microscopes. Our in situ reduction studies
      show that many of the oxide particles form voids when reduced to Pd metal. The
      decrease in volume that occurs during reduction is often accommodated by a
      combination of particle shrinkage and void formation. The production of voids
      does not seem to depend on either the reducing atmosphere or the rate of
      reduction, although the voids appear to be unstable above 500 degreesC.

PMID- 9767666
TI  - In Situ Observations of the Interaction of Liquid Lead Inclusions with Grain
      Boundaries in Aluminum.
AB  - : The evolution of liquid lead (Pb) inclusions at grain boundaries in aluminum
      (Al) was investigated by direct in situ TEM observation in the temperature range
      from 330 degrees-643 degreesC. In agreement with earlier reports on quenched
      alloys, the characteristic contact angle of the lens-shaped grain boundary
      inclusions was found to be near 120 degrees. This angle remained approximately
      constant over the entire temperature range, ruling out the possibility of a
      wetting transition. Coarsening of grain boundary inclusions was observed to
      proceed mainly by Ostwald ripening, although coalescence could also be observed.
      Inclusions at grain boundaries, at triple junctions, and at the intersection of
      grain boundaries with the foil surfaces adopted characteristic shapes that were
      shown to be equilibrium forms. At the highest temperatures, the grain boundaries
      were observed to detach from the inclusions and the interaction of a migrating
      grain boundary with inclusions could be observed.

PMID- 9767667
TI  - In Situ Studies of the Interaction of Dislocations with Point Defects during
      Annealing of Ion Implanted Si/SiGe/Si (001) Heterostructures.
AB  - : Strained layer heterostructures provide ideal systems with which to study the
      dynamics of dislocation motion via in situ transmission electron microscopy, as
      the geometry, strain state, and kinetics can be characterized and directly
      controlled. We discuss how these structures are used to study dislocation-point
      defect interactions, emphasizing the experimental requirements necessary for
      quantification of dislocation motion. Following ion implantation, different
      concentrations and types of point defects are introduced within the SiGe epilayer
      depending on the implantation species, energy, and current density. By annealing
      samples in situ in the transmission electron microscope (TEM) following
      implantation, we can directly observe dislocation motion and quantify the effect
      of dislocation-point defect interactions on dislocation velocities. We find that
      dislocation motion is impeded if the implantation dose peak lies within the
      epilayer, as dislocations pin at point defect atmospheres. Shallow BF2
      implantation into the sample capping layer results in more complicated behavior.
      For low current density implants, dislocation velocities may be dramatically
      increased; at higher current densities the magnitude of this increase is
      significantly smaller. Implantation of different ions separately implicates
      fluorine as the species responsible for the observed increases in dislocation
      velocities, presumably due to an electrical effect on the rate of dislocation
      kink nucleation.

PMID- 9767668
TI  - Applications of Ion Microscopy and In Situ Electron Microscopy to the Study of
      Electronic Materials and Devices.
AB  - : We discuss the application of ion microscopy and in situ electron microscopy to
      the study of electronic and optical materials and devices. We demonstrate how the
      combination of in situ transmission electron microscopy and focused ion beam
      microscopy provides new avenues for the study for such structures, enabling
      extension of these techniques to the study of dopant distributions, nanoscale
      stresses, three-dimensional structural and chemical reconstruction, and real-time
      evolution of defect microstructure. We also discuss in situ applications of
      thermal, mechanical, electrical, and optical stresses during transmission
      electron microscopy imaging.

PMID- 9767669
TI  - In Situ Transmission Electron Microscopy Observations of Silicidation Processes
      for Cobalt Thin Films Deposited on Silicon.
AB  - : Morphological evolution associated with silicidation of Co thin films deposited
      on (100) and (111) Si substrates has been followed using transmission electron
      microscopy with in situ thermal annealing from ambient temperature up to 850
      degreesC. Noticeable structural changes associated with the formation of CoSi2
      occur at temperatures as low as 400 degreesC and the reaction is essentially
      complete at about 500 degreesC. Prolonged heating above 500 degreesC leads to
      CoSi2 grain growth and coalescence and, finally, to pinholes formation.
      Silicidation of Co films on (100) and (111) Si substrates follows the same
      pattern. The morphology of films annealed in situ is similar to those annealed ex
      situ except that the Si/CoSi2 interface appears to be much rougher. This behavior
      is associated with the specific geometry of cross-sectional TEM specimens, where
      surface diffusion dominates bulk diffusion. Very thin Co films, which have less
      contribution from surface diffusion than thicker films, are ideal for studying
      dynamic phenomena at Co/Si reactive interfaces.

PMID- 9767670
TI  - In Situ Transmission Electron Microscopy Studies of the Magnetization Reversal
      Mechanism in Information Storage Materials.
AB  - : The Foucault and Fresnel modes of Lorentz microscopy, together with a
      quantitative magnetization mapping technique, summed image differential phase
      contrast imaging, were used to study the magnetization reversal mechanism of the
      sense layer in spin-valve structures exhibiting the giant magnetoresistance
      effect. In addition to studies of sheet film, lithographically defined spin-valve
      elements were investigated. A current can be passed through the element during
      magnetizing so that the effect of the applied current on the giant
      magnetoresistance and magnetization reversal mechanism can be studied. Results
      are presented for a number of different spin-valve structures.

PMID- 9767672
TI  - News and Commentary.

PMID- 9767671
TI  - Surface Reconstruction and Oxide Nucleation Due to Oxygen Interaction with
      Cu(001) Observed by In Situ Ultra-High Vacuum Transmission Electron Microscopy.
AB  - : Reconstruction of the Cu(001) surface due to oxygen gas impingement on a clean
      copper surface was directly observed by in situ UHV-TEM. Strain contrast between
      differently oriented surface reconstruction domains, assumed to be radical2 x 2
      radical2 R45, were clearly visible by this method. The reconstruction precedes
      the nucleation of Cu2O islands. When Cu2O islands were partially reduced and then
      re-oxidized, a dwell time before formation of Cu2O was noted, demonstrating that
      a reconstructed Cu-O surface monolayer is necessary before oxide formation.

PMID- 9767673
TI  - Integrin signaling: tyrosine phosphorylation events in focal adhesions.

PMID- 9767675
TI  - Charge displacements in interfacial layers containing reaction centers.
AB  - Reaction centers from the photosynthetic bacterium Rhodobacter sphaeroides were
      oriented in phospholipid interfacial layers adsorbed to a Teflon film separating
      two electrolyte-filled compartments of a Teflon cell. Light-induced voltage
      changes were measured as a function of time across electrodes immersed in the
      cell compartments. The experimental system is characterized both experimentally
      and theoretically to relate the measured signals to the light-induced
      displacement currents in the reaction centers. Mathematical relations between the
      measured signals and the distances and geometries of the charge-transfer
      reactions are derived. At pH 8.0 the reaction centers were found to be oriented
      with approximately 60% of the population oriented with the donor facing the
      aqueous phase. The density of the reaction centers in the layer was approximately
      10(11) cm-2, which is close to that found in the native system. Reconstitution of
      the secondary quinone, QB, in 90% of the RCs was achieved with an approximately
      100-fold excess of ubiquinone in the vesicle preparation.

PMID- 9767674
TI  - Blood-brain barrier permeation: molecular parameters governing passive diffusion.
AB  - 53 compounds with clinically established ability to cross or not to cross the
      blood-brain barrier by passive diffusion were characterized by means of surface
      activity measurements in terms of three parameters, i.e., the air-water partition
      coefficient, Kaw, the critical micelle concentration, CMCD, and the cross
      sectional area, AD. A three-dimensional plot in which the surface area, AD, is
      plotted as a function of K-1aw and CMCD shows essentially three groups of
      compounds: (i) very hydrophobic compounds with large air-water partition
      coefficients and large cross-sectional areas, AD > 80 A2 which do not cross the
      blood-brain barrier, (ii) compounds with lower air-water partition coefficients
      and an average cross-sectional area, AD congruent with 50 A2 which easily cross
      the blood-brain barrier, and (iii) hydrophilic compounds with low air-water
      partition coefficients (AD < 50 A2) which cross the blood-brain barrier only if
      applied at high concentrations. It was shown that the lipid membrane-water
      partition coefficient, Klw, measured previously, can be correlated with the air
      water partition coefficient if the additional work against the internal lateral
      bilayer pressure, pibi = 34 +/- 4 mN/m is taken into account. The partitioning
      into anisotropic lipid membranes decreases exponentially with increasing cross
      sectional areas, AD, according to Klw = const. Kaw exp(-ADpibi/kT) where kT is
      the thermal energy. The cross-sectional area of the molecule oriented at a
      hydrophilic-hydrophobic interface is thus the main determinant for membrane
      permeation provided the molecule is surface active and has a pKa > 4 for acids
      and a pKa < 10 for bases.

PMID- 9767676
TI  - Nitric oxide inhibition of the rat olfactory cyclic nucleotide-gated cation
      channel.
AB  - The effects of nitric oxide (NO) and other cysteine modifying agents were
      examined on cyclic nucleotide-gated (CNG) cation channels from rat olfactory
      receptor neurons. The NO compounds, S-nitroso-cysteine (SNC) and 3-morpholino
      sydnonomine (SIN-1), did not activate the channels when applied for up to 10 min.
      The cysteine alkylating agent, N-ethylmaleimide (NEM), and the oxidising agent,
      dithionitrobensoate (DTNB), were also without agonist efficacy. Neither SNC nor
      DTNB altered the cAMP sensitivity of the channels. However, 2-min applications of
      SIN-1, SNC and DTNB inhibited the cAMP-gated current to approximately 50% of the
      control current level. This inhibition showed no spontaneous reversal for 5 min
      but was completely reversed by a 2-min exposure to DTT. The presence of cAMP
      protected the channels against NO-induced inhibition. These results indicate that
      inhibition is caused by S-nitrosylation of neighboring sulfhydryl groups leading
      to sulfhydryl bond formation. This reaction is favored in the closed channel
      state. Since recombinantly expressed rat olfactory alpha and beta CNG channel
      homomers and alpha/beta heteromers are activated and not inhibited by cysteine
      modification, the results of this study imply the existence of a novel subunit or
      tightly bound factor which dominates the effect of cysteine modification in the
      native channels. As CNG channels provide a pathway for calcum influx, the results
      may also have important implications for the physiological role of NO in
      mammalian olfactory receptor neurons.

PMID- 9767677
TI  - Simple carrier kinetics in complex membrane transporters.
AB  - The four-state simple carrier model (SCM) has been employed to describe
      facilitative transport of ligands across biological membranes. Two basic
      mechanisms have been invoked to account for carrier-mediated ligand
      translocation: (i) binding to a mobile carrier, and (ii) displacement determined
      by conformational changes of an integral protein. While translatory carriers may
      be accurately represented by a four-state diagram, it is unlikely that the
      transport process mediated by a complex membrane protein can be strictly
      described by the elementary SCM. The purpose of this article is to test whether
      facilitative transporters with a more complex kinetic design than the SCM can
      exhibit macroscopic kinetic properties indistinguishable from it. For this, I
      studied a "general carrier model" (GCM), and evaluated whether the relevant
      kinetic parameters are subject to the same basic restrictions as in the SCM. The
      fundamental finding is that there is a general kinetic design embodied with SCM
      like properties, that can be shared by many transporters. In particular, the
      classical SCM is shown here to represent a particular case of the GCM. A main
      conclusion of this work is therefore that the finding of a macroscopic SCM-like
      kinetic behavior for a particular process of facilitative transport does not
      represent a sufficient argument in favor of a particular type of mechanism, like
      the typical one involving a two-conformational single-site carrier.

PMID- 9767678
TI  - Freeze-fracture analysis of plasma membranes of CHO cells stably expressing
      aquaporins 1-5.
AB  - Several studies suggest that aquaporin water channels can be identified in
      membranes by freeze-fracture electron microscopy. For this report, Chinese
      Hamster ovary cells were stably transfected with cDNAs encoding aquaporins 1-5.
      Measurement of the osmotic water permeability of the cells confirmed that
      functional protein was expressed and delivered to the plasma membrane. By freeze
      fracture electron microscopy, a 20% increase in intramembrane particle (IMP)
      density was found in plasma membranes of cells expressing AQP2, 3 and 5, and a
      100% increase was measured in AQP1-expressing cells, when compared to mock
      transfected cells. On membranes of cells expressing AQP4, large aggregates of
      IMPs were organized into orthogonal arrays, which occupied 10-20% of the membrane
      surface. IMP aggregates were never seen in AQP2-transfected cells. Hexagonally
      packed IMP clusters were detected in approximately 5% of the membranes from AQP3
      expressing cells. Particle size-distribution analysis of rotary shadowed IMPs
      showed a significant shift from 13. 5 (control cells) to 8.5 nm or less in AQP
      expressing cells; size distribution analysis of unidirectionally shadowed IMPs
      also showed a significant change when compared to control. Some IMPs in AQP
      expressing cells had features consistent with the idea that aquaporins are
      assembled as tetramers. The results demonstrate that in transfected CHO cells,
      AQP transfection modifies the general appearance and number of IMPs on the plasma
      membrane, and show that only AQP4 assembles into well-defined IMP arrays.

PMID- 9767679
TI  - Biophysical characteristics of swelling-activated Cl- channels in human tracheal
      9HTEo-cells.
AB  - The question of whether a single molecule can account for every observed swelling
      activated Cl- current deserves to be addressed and biophysical description seems
      to be an adequate criterion to classify these channels. We studied the
      biophysical properties of swelling-activated Cl- currents in 9HTEo-cells using
      whole-cell and outside-out patch clamp recordings. Hypotonic shock activated
      outwardly rectifying currents that inactivated at potentials higher than 20 mV.
      The decay phase of the current was well fitted by two exponential functions and
      both time constants were voltage-dependent. Two voltage-dependent time constants
      were also necessary to describe reactivation. The midpoint of current
      inactivation was 54 mV. The voltage dependence of kinetics did not significantly
      change by modifying the extracellular NaCl concentration while the inactivation
      midpoint slightly shifted. In conclusion, our results indicate that the voltage
      dependent properties of the swelling-activated Cl- currents in 9HTEo- cells are
      largely independent from the extracellular ionic strength and the extracellular
      Cl- concentration. Excised patches from cells exposed to hypotonic shock showed
      single channel currents that inactivated at positive membrane potentials and
      displayed chord conductance of approximately 60 pS at 100 mV and of approximately
      20 pS at -80 mV. The permeability sequence for the single channel was I- > Br- >
      Cl- > gluconate and currents were blocked by Reactive blue 2. These properties
      indicate that intermediate conductance outwardly rectifying channels are
      responsible for the macroscopic swelling-activated current.

PMID- 9767680
TI  - Characterization of the Na+/H+ exchanger in the luminal membrane of the distal
      nephron.
AB  - In the rabbit as well as the rat, a Na+/H+ exchanger is expressed in the apical
      membrane of both the proximal and distal tubules of the renal cortex. Whereas the
      isoform derived from the proximal tubule has been extensively studied, little
      information is available concerning the distal luminal membrane isoform. To
      better characterize the latter isoform, we purified rabbit proximal and distal
      tubules, and examined the ethylpropylamiloride (EIPA)-sensitive 22Na uptake by
      the luminal membrane vesicles from the two segments. The presence of 100 micron
      EIPA in the membrane suspension decreased the 15 sec Na+ uptake to 75.70 +/-
      4.70% and 50.30 +/- 2.23% of the control values in vesicles from proximal and
      distal tubules, respectively. The effect of EIPA on 35 mM Na+ uptake was
      concentration dependent, with a IC50 of 700 micron and 75 micron for the proximal
      and distal luminal membranes. Whereas the proximal tubule membrane isoform was
      insensitive to cimetidine and clonidine up to a concentration of 2 mM, the 35 mM
      Na+ uptake by the distal membrane was strongly inhibited by cimetidine (IC50 700
      micron) and modestly inhibited by clonidine (IC50 1.6 mM). The incubation of
      proximal tubule suspensions with 1 mM (Bu2) cAMP decreased the 15-sec EIPA
      sensitive Na+ uptake by the brush border membranes to 24.1 +/- 2.38% of the
      control values. Unexpectedly, the same treatment of distal tubules enhanced this
      uptake by 46.5 +/- 10.3%. Finally, incubation of tubule suspensions with 100 nm
      phorbol 12-myristate 13-acetate (PMA) decreased the exchanger activity to 58.6 +/
      3.04% and 79.7 +/- 3.21% of the control values in the proximal and distal
      luminal membranes, respectively. In conclusion, the high sensitivity of the
      distal luminal membrane exchanger to various inhibitors, and its stimulation by
      cAMP-dependent protein kinase A, indicate that this isoform differs from that of
      the proximal tubule and probably corresponds to isoform 1.

PMID- 9767681
TI  - Na+-coupled alanine transport in LLC-PK1 cells: the relationship between the Km
      for Na+ at low [Alanine] and potential dependence for the system.
AB  - Analysis of the mechanistic basis by which sodium-coupled transport systems
      respond to changes in membrane potential is inherently complex. Algebraic
      expressions for the primary kinetic parameters (Km and Vmax) consist of multiple
      terms that encompass most rate constants in the transport cycle. Even for a
      relatively simple cotransport system such as the Na+/alanine cotransporter in LLC
      PK1 cells (1:1 Na+ to substrate coupling, and an ordered binding sequence), the
      algebraic expressions for Km for either substrate includes ten of the twelve rate
      constants necessary for modeling the full transport cycle. We show here that the
      expression of Km of the first-bound substrate (Na+) simplifies markedly if the
      second-bound substrate (alanine) is held at a low concentration so that its'
      binding becomes the rate limiting step. Under these conditions, the expression
      for the KNam includes rate constants for only two steps in the full cycle: (i)
      binding/dissociation of Na+, and (ii) conformational 'translocation' of the
      substrate-free protein. The influence of imposed changes in membrane potential on
      the apparent KNam for the LLC-PK1 alanine cotransporter at low alanine thus
      provides insight to potential dependence at these sites. The data show no
      potential dependence for KNam at 5 micron alanine, despite marked potential
      dependence at 2 mm alanine when the full algebraic expression applies. The
      results suggest that neither translocation of the substrate-free form of the
      transporter nor binding/dissociation of extracellular sodium are potential
      dependent events for this transport system.

PMID- 9767682
TI  - Site-specific prebiotic oligomerization reactions of glycine on the surface of
      hectorite.
AB  - Condensation reactions of the amino acid glycine on the surface of Cu(II)
      exchanged hectorite are investigated using the technique of scanning force
      microscopy. Prebiotic conditions are simulated using alternate wetting and
      heating cycles. Concentration, immobilization, and subsequent polymerization
      resulting in glycine oligomers are seen to occur primarily at step edges or
      faults in the topmost layer. Condensation reactions also occur within tiny
      micropores or defects in the topmost layer. These reactions are facilitated by
      the availability of intergallery metal cations at the step edges or pores in the
      surface region.

PMID- 9767684
TI  - Biased usages of arginines and lysines in proteins are correlated with local
      scale fluctuations of the G + C content of DNA sequences.
AB  - Amino acid residues arginine (R) and lysine (K) have similar physicochemical
      characteristics and are often mutually substituted during evolution without
      affecting protein function. Statistical examinations on human proteins show that
      more R than K residues are used in the proximity of R residues, whereas more K
      than R are used near K residues. This biased use occurs on both a global and a
      local scale (shorter than approximately 100 residues). Even within a given exon,
      G + C-rich and A + T-rich short DNA segments preferentially encode R and K,
      respectively. The biased use of R and K on a local scale is also seen in
      Saccharomyces cerevisiae and Caenorhabdidtis elegans, which lack global-scale
      mosaic structures with varying GC%, or isochores. Besides R and K, several amino
      acids are also used with a positive or negative correlation with the local GC% of
      third codon bases. The local-, or "within-gene"-, scale heterogeneity of the DNA
      sequence may influence the sequence of the encoded protein segment.

PMID- 9767683
TI  - Directionally evolving genetic code: the UGA codon from stop to tryptophan in
      mitochondria.
AB  - For the comprehensive analyses of deviant codes in protistan mitochondria (mt),
      we sequenced about a 1.1-kb region of a mitochondrial (mt) gene, the cytochrome c
      oxidase subunit I (coxI) in two chlorarachniophytes, the filose amoeba Euglypha
      rotunda, the cryptomonad Cryptomonas ovata, the prymnesiophyte (haptophyte)
      Diacronema vlkianum (Pavlovales), and the diatom Melosira ambigua. As a result of
      this analysis, we noticed that the UGA codon is assigned to tryptophan (Trp)
      instead of being a signal for translational termination in two
      chlorarachniophytes and in E. rotunda. The same type of deviant code was reported
      previously in animals, fungi, ciliates, kinetoplastids, Chondrus crispus (a red
      alga), Acanthamoeba castellanii (an amoeboid protozoon), and three of the four
      prymnesiophyte orders with the exception of the Pavlovales. A phylogenetic
      analysis based on the COXI sequences of 56 eukaryotes indicated that the
      organisms bearing the modified code, UGA for Trp, are not monophyletic. Based on
      these studies, we propose that the ancestral mitochondrion was bearing the
      universal genetic code and subsequently reassigned the codon to Trp
      independently, at least in the lineage of ciliates, kinetoplastids, rhodophytes,
      prymnesiophytes, and fungi. We also discuss how this codon was directionally
      captured by Trp tRNA.

PMID- 9767685
TI  - Limitations of metazoan 18S rRNA sequence data: implications for reconstructing a
      phylogeny of the animal kingdom and inferring the reality of the Cambrian
      explosion.
AB  - We document the phylogenetic behavior of the 18S rRNA molecule in 67 taxa from 28
      metazoan phyla and assess the effects of among-site rate variation on
      reconstructing phylogenies of the animal kingdom. This empirical assessment was
      undertaken to clarify further the limits of resolution of the 18S rRNA gene as a
      phylogenetic marker and to address the question of whether 18S rRNA phylogenies
      can be used as a source of evidence to infer the reality of a Cambrian explosion.
      A notable degree of among-site rate variation exists between different regions of
      the 18S rRNA molecule, as well as within all classes of secondary structure.
      There is a significant negative correlation between inferred number of nucleotide
      substitutions and phylogenetic information, as well as with the degree of
      substitutional saturation within the molecule. Base compositional differences
      both within and between taxa exist and, in certain lineages, may be associated
      with long branches and phylogenetic position. Importantly, excluding sites with
      different degrees of nucleotide substitution significantly influences the
      topology and degree of resolution of maximum-parsimony phylogenies as well as
      neighbor-joining phylogenies (corrected and uncorrected for among-site rate
      variation) reconstructed at the metazoan scale. Together, these data indicate
      that the 18S rRNA molecule is an unsuitable candidate for reconstructing the
      evolutionary history of all metazoan phyla, and that the polytomies, i.e.,
      unresolved nodes within 18S rRNA phylogenies, cannot be used as a single or
      reliable source of evidence to support the hypothesis of a Cambrian explosion.

PMID- 9767686
TI  - Trematode and monogenean rRNA ITS2 secondary structures support a four-domain
      model.
AB  - The secondary structure of rRNA internal transcribed spacer 2 is important in the
      process of ribosomal biogenesis. Trematode ITS sequences are poorly conserved and
      difficult to align for phylogenetic comparisons above a family level. If a
      conserved secondary structure can be identified, it can be used to guide primary
      sequence alignments. ITS2 sequences from 39 species were compared. These species
      span four orders of trematodes (Echinostomiformes, Plagiorchiformes,
      Strigeiformes, and Paramphistomiformes) and one monogenean (Gyrodactyliformes).
      The sequences vary in length from 251 to 431 bases, with an average GC content of
      48%. The monogenean sequence could not be aligned with confidence to the
      trematodes. Above the family level trematode sequences were alignable from the 5'
      end for 139 bases. Secondary structure foldings predicted a four-domain model.
      Three folding patterns were required for the apex of domain B. The folding
      pattern of domains C and D varies for each family. The structures display a high
      GC content within stems. Bases A and U are favored in unpaired regions and
      variable sites cluster. This produces a mosaic of conserved and variable regions
      with a structural conformation resistant to change. Two conserved strings were
      identified, one in domain B and the other in domain C. The first site can be
      aligned to a processing site identified in yeast and rat. The second site has
      been found in plants, and structural location appears to be important. A
      phylogenetic tree of the trematode sequences, aligned with the aid of secondary
      structures, distinguishes the four recognized orders.

PMID- 9767687
TI  - Phylogenetic position of the Phacotaceae within the Chlamydophyceaeas revealed by
      analysis of 18S rDNA and rbcL sequences.
AB  - Four genera of the Phacotaceae (Phacotus, Pteromonas, Wislouchiella,
      Dysmorphococcus), a family of loricated green algal flagellates within the
      Volvocales, were investigated by means of transmission electron microscopy and
      analysis of the nuclear encoded small-subunit ribosomal RNA (18S rRNA) genes and
      the plastid-encoded rbcL genes. Additionally, the 18S rDNA of Haematococcus
      pluvialis and the rbcL sequences of Chlorogonium elongatum, C. euchlorum,
      Dunaliella parva, Chloromonas serbinowii, Chlamydomonas radiata, and C. tetragama
      were determined. Analysis of ultrastructural data justified the separation of the
      Phacotaceae into two groups. Phacotus, Pteromonas, and Wislouchiella generally
      shared the following characters: egg-shaped protoplasts, a single pyrenoid with
      planar thylakoid double-lamellae, three-layered lorica, flagellar channels as
      part of the central lorica layer, mitochondria located in the central cytoplasm,
      lorica development that occurs in mucilaginous zoosporangia that are to be lysed,
      and no acid-resistant cell walls. Dysmorphococcus was clearly different in each
      of the characters mentioned. Direct comparison of sequences of Phacotus
      lenticularis, Pteromonas sp., Pteromonas protracta, and Wislouchiella planctonica
      revealed DNA sequence homologies of >/=98. 0% within the 18S gene and 93.9%
      within the rbcL gene. D. globosus was quite different from these species, with a
      maximum of 92.9% homology in the 18S rRNA and </=86.6% in the rbcL gene. It
      showed major similarities to the 18S rDNA of Dunaliella salina, with 95.3%, and
      to the rbcL sequence of Chlamydomonas tetragama, with 90.3% sequence homology.
      Additionally, the Phacotaceae sensu stricto exclusively shared 10 (rbcL: 4)
      characters which were present neither in other Chlamydomonadales nor in
      Dysmorphococcus globosus. Different phylogenetic analysis methods confirmed the
      hypothesis that the Phacotaceae are polyphyletic. The Phacotaceae sensu stricto
      form a stable cluster with affinities to the Dunaliellaes and possibly
      Haematococcus pluvialis. Dysmorphococcus globosus represented an independent
      lineage that is possibly related to Chlamydomonas moewusii and C. tetragama.

PMID- 9767688
TI  - The mitochondrial genome of Chlorogonium elongatum inferred from the complete
      sequence.
AB  - The 22,704-bp circular mitochondrial DNA (mtDNA) of the chlamydomonad alga
      Chlorogonium elongatum was completely cloned and sequenced. The genome encodes
      seven proteins of the respiratory electron transport chain, subunit 1 of the
      cytochrome oxidase complex (cox1), apocytochrome b (cob), five subunits of the
      NADH dehydrogenase complex (nad1, nad2, nad4, nad5, and nad6), a set of three
      tRNAs (Q, W, M), and the large (LSU)- and small (SSU)-subunit ribosomal RNAs. Six
      group-I introns were found, two each in the cox1, cob, and nad5 genes. In each
      intron an open reading frame (ORF) related to maturases or endonucleases was
      identified. Both the LSU and the SSU rRNA genes are split into fragments
      intermingled with each other and with other genes. Although the average A + T
      content is 62.2%, GC-rich clusters were detected in intergenic regions, in
      variable domains of the rRNA genes, and in introns and intron-encoded ORFs. A
      comparison of the genome maps reveals that C. elongatum and Chlamydomonas
      eugametos mtDNAs are more closely related to one another than either is to
      Chlamydomonas reinhardtii mtDNA.

PMID- 9767689
TI  - The complete mitochondrial DNA sequence of the domestic sheep (Ovis aries) and
      comparison with the other major ovine haplotype.
AB  - The complete mitochondrial DNA (mtDNA) molecule of the domestic sheep, Ovis
      aries, was sequenced, together with part of the mtDNA of a specimen representing
      the other major O. aries haplotype group. The length of the complete ovine mtDNA
      presented is 16,616 nucleotides (nt). This length is not absolute, however, due
      to heteroplasmy caused by the occurrence of different numbers of a 75-nt-long
      tandem repeat in the control region. The sequence data were included in analyses
      of intraspecific ovine molecular differences, molecular comparisons with bovine
      mtDNAs, and phylogenetic analyses based on complete mtDNAs. The comparisons with
      bovine mtDNAs were based on the central domains of the ovine control regions,
      representing both major ovine haplotype groups, and the corresponding domains of
      Bos taurus and B. indicus. The comparisons showed that the difference between the
      bovids was 1.4 times greater than the intraspecific ovine difference. These
      findings suggest that the strains of wild sheep from which domestic sheep
      originated were more closely related than were the B. primigenius subspecies
      which gave rise to B. indicus and B. taurus cattle. Datings based on complete
      mtDNAs suggest that the bovine and ovine lineages diverged about 30 million years
      before present. This dating is considerably earlier than that proposed
      previously.

PMID- 9767690
TI  - Organization and evolution of the mitochondrial DNA control region in the avian
      genus Alectoris.
AB  - The entire mitochondrial DNA control region (mtDNA D-loop) was sequenced in the
      seven extant species of Alectoris partridges. The D-loop length is very conserved
      (1155 +/- 2 nucleotides), and substitution rates are lower than for the
      mitochondrial cytochrome b gene of the same species, on average. Comparative
      analyses suggest that these D-loops can be divided into three domains,
      corresponding to the highly variable peripheral domains I and III and to the
      central conserved domain II of vertebrates (Baker and Marshall 1997).
      Nevertheless, the first 161 nucleotides of domain I of the Alectoris, immediately
      flanking the tRNAGlu, evolve at an unusually low rate and show motifs similar to
      the mammalian extended termination-associated sequences [ETAS1 and ETAS2 (Sbisa
      et al. 1997)], which can form stable secondary structures. The second part of
      domain I contains a hypervariable region with two divergent copies of a tandemly
      repeated sequence described previously in other species of anseriforms and
      galliforms (Quinn and Wilson 1993; Fumihito et al. 1995). Some of the conserved
      sequence blocks of mammals can be mapped in the central domain of Alectoris.
      Domain III is highly variable and has sequences similar to mammalian CSB1. The
      bidirectional transcription promoter HSP/LSP box of the chicken is partially
      conserved among the Alectoris. This structural organization can be found in the
      anseriform and galliform species studied so far, suggesting that strong
      functional constraints might have controlled the evolution of the D-loop since
      the origin of Galloanserae. Their conserved organization and slow molecular
      evolution make D-loops of galliforms appropriate for phylogenetic studies,
      although homoplasy can be be generated at a few hypervariable sites and at some
      sites which probably have mutated by strand slippage during DNA replication.
      Phylogenetic analyses of D-loops of Alectoris are concordant with previously
      published cytochrome b and allozyme phylogenies (Randi 1996). Alectoris is
      monophyletic and includes three major clades: (1) basal barbara and
      melanocephala; (2) intermediate rufa and graeca; and (3) recent philbyi, magna,
      and chukar. Comparative description of the organization and substitution patterns
      of the mitochondrial control region can aid in mapping hypervariable sites and
      avoid some sources of homoplasy in data sets which are to be used in phylogenetic
      analyses.

PMID- 9767691
TI  - Similar target site selection occurs in integration of plant and mammalian
      retroposons.
AB  - The reverse transcription of RNA in DNA is responsible for the generation of
      large families of repetitive sequences called retroposons or non-LTR
      retrotransposons. Recent reports established that the integration of mammalian
      SINE and LINE retroposons occurs at nonrandom staggered breaks, probably
      resulting from the action of a LINE-encoded endonuclease (Feng et al. 1996; Jurka
      1997; Jurka et al. 1998). We report here that plant SINE S1 retroposons also
      integrate at nonrandom staggered breaks. One of the two nicks involved in S1
      integration is associated mainly with the 5'-Y/AAANNNG-3' motif. The other nick
      at opposite DNA strand occurs preferably within 14-16 bp, a situation also
      observed for mammalian retroposons, but is not associated with any specific
      motif. Further studies on the distribution of dinucleotides surrounding the two
      nicking sites showed that, as for mammalian retroposons, S1 retroposons integrate
      at sites rich in TA, CA, and TG dinucleotides. These dinucleotides were reported
      as specific DNA sites where special DNA structures called "kinks" may occur under
      bending constraints. Nicking sites are preceded by peaks in frequency of di
      pyrimidine followed by peaks of di-purine. These results suggest that the general
      A/T richness of a given DNA region and the presence of short runs of pyrimidines
      followed by short runs of purines could represent a favorable context for the
      integration of retroposons. In such a context, an endonuclease upon fixation
      could be able to generate the kink at the pyrimidine/purine transition and to
      nick the DNA. The similarities in target site selection observed for plant and
      mammalian retroposons suggest that retroposition is a surprisingly well conserved
      process.

PMID- 9767692
TI  - Phylogenetic analysis of reptilian hemoglobins: trees, rates, and divergences.
AB  - Phylogenetic relationships among reptiles were examined using previously
      published and newly determined hemoglobin sequences. Trees reconstructed from
      these sequences using maximum-parsimony, neighbor-joining, and maximum-likelihood
      algorithms were compared with a phylogenetic tree of Amniota, which was assembled
      on the basis of published morphological data. All analyses differentiated alpha
      chains into alphaA and alphaD types, which are present in all reptiles except
      crocodiles, where only alphaA chains are expressed. The occurrence of the alphaD
      chain in squamates (lizards and snakes only in this study) appears to be a
      general characteristic of these species. Lizards and snakes also express two
      types of beta chains (betaI and betaII), while only one type of beta chain is
      present in birds and crocodiles. Reconstructed hemoglobin trees for both alpha
      and beta sequences did not yield the monophyletic Archosauria (i.e., crocodilians
      + birds) and Lepidosauria (i.e., Sphenodon + squamates) groups defined by the
      morphology tree. This discrepancy, as well as some other poorly resolved nodes,
      might be due to substantial heterogeneity in evolutionary rates among single
      hemoglobin lineages. Estimation of branch lengths based on uncorrected amino acid
      substitutions and on distances corrected for multiple substitutions (PAM
      distances) revealed that relative rates for squamate alphaA and alphaD chains and
      crocodilian beta chains are at least twice as high as those of the rest of the
      chains considered. In contrast to these rate inequalities between reptilian
      orders, little variation was found within squamates, which allowed determination
      of absolute evolutionary rates for this subset of hemoglobins. Rate estimates for
      hemoglobins of lizards and snakes yielded 1.7 (alphaA) and 3.3 (beta) million
      years/PAM when calibrated with published divergence time vs. PAM distance
      correlates for several speciation events within snakes and for the squamate left
      and right arrow sphenodontid split. This suggests that hemoglobin chains of
      squamate reptiles evolved approximately 3.5 (alphaA) or approximately 1.7 times
      (beta) faster than their mammalian equivalents. These data also were used to
      obtain a first estimate of some intrasquamate divergence times.

PMID- 9767693
TI  - Sequence peculiarity of gnetalean legumin-like seed storage proteins.
AB  - The development of seeds as a specialized organ for the nutrition, protection,
      and dispersal of the next generation was an important step in the evolution of
      land plants. Seed maturation is accompanied by massive synthesis of storage
      compounds such as proteins, starch, and lipids. To study the processes of seed
      storage protein evolution we have partially sequenced storage proteins from
      maturing seeds of representatives from the gymnosperm genera Gnetum, Ephedra, and
      Welwitschia-morphologically diverse and unusual taxa that are grouped in most
      formal systems into the common order Gnetales. Based on partial N-terminal amino
      acid sequences, oligonucleotide primers were derived and used for PCR
      amplification and cloning of the corresponding cDNAs. We also describe the
      structure of the nuclear gene for legumin of Welwitschia mirabilis. This first
      gnetalean nuclear gene structure contains introns in only two of the four
      conserved positions previously characterized in other spermatophyte legumin
      genes. The distinct phylogenetic status of the gnetalean taxa is also reflected
      in a sequence peculiarity of their legumin genes. A comparative analysis of
      exon/intron sequences leads to the hypothesis that legumin genes from Gnetales
      belong to a monophyletic evolutionary branch clearly distinct from that of
      legumin genes of extant Ginkgoales and Coniferales as well as from all
      angiosperms.

PMID- 9767694
TI  - Sensitivity of patterns of molecular evolution to alterations in methodology: a
      critique of Hughes and Yeager.
AB  - Employing a set of 43 othologous mouse and rat genes, Hughes and Yeager (J. Mol.
      Evol. 45:125-130, 1997) reported (1) no correlation between synonymous and
      nonsynonymous rates of nucleotide substitution, (2) a positive correlation
      between intronic GC contents (GCi) and intronic substitution rates (Ki), (3) that
      the average Ki value was very similar to the average Ks value, and (4) that the
      compositional correlation between the rat and the mouse genes is stronger at the
      third codon position (GC3) than at the first and second codon positions (GC12).
      We have examined the robustness of these results to alterations in substitution
      rate estimation protocol, alignment protocol, and statistical procedure. We find
      that a significant correlation between Ka and Ks is observed either if a rank
      correlation statistic is used instead of regression analysis, if one outlier is
      excluded from the analysis, or if a regression weighted by gene size is employed.
      The correlation between Ki and GCi we find to be sensitive to changes in
      alignment protocol and disappears on the use of weighted means. The finding that
      Ks and Ki are approximately the same is dependent on the method for estimating Ks
      values. Finally, the variance around the regression line of rat GC3 versus mouse
      GC3 we find to be significantly higher than that in GC12. The source of the
      discrepancy between this and Hughes and Yeager's result is unclear. The variance
      around the line for GC4 is higher still, as might be expected. Using a
      methodology that may be considered preferable to that of Hughes and Yeager, we
      find that all four of their results are contradicted. More importantly this
      analysis reinforces the need for caution in assembling and analyzing data sets,
      as the degree of sensitivity to what many might consider minor methodological
      alterations is unexpected.

PMID- 9767695
TI  - Midiabdominoplasty: indications and technique.
AB  - In the treatment of aesthetic deformities of the abdomen there are three points
      we should analyze: the skin, the fat tissue, and the muscles. Based on these
      points we can classify it into six groups. Midiabdominoplasty is indicated in the
      correction of deformities of groups 2, 3, and 4. A small fusiform resection of
      skin is done in the lower abdomen, undermining of the skin up to the umbilicus
      (or to the xiphoid appendix if necessary to treat diastasis of the rectus muscles
      in the supraumbilical region), and desinsertion of the umbilicus, with no
      external scar, are the main points in this technique. The main complication was
      the formation of seroma. No necrosis of the flap or unsightly scars were
      observed. The results were good, with the patients satisfied with their new
      abdomens.

PMID- 9767696
TI  - High-tech facelift.
AB  - Recent technological advances in our specialty have made us reappraise the way we
      approach facial rejuvenation. Some of these technological interfaces have made it
      possible, in the author's experience, to improve results and to tackle difficult
      aesthetic problems. The purpose of this paper is to report how we combine these
      technological advances in an effort to improve the aesthetic outcomes. These
      technological advances are: laser skin resurfacing, endoscopy, newer fat grafting
      procedures, and new alloplastic materials for bone augmentation. Other
      technological advances are consultations via the Internet, computer imaging for
      simulation of possible outcomes, etc. Endoscopy is routinely used in our facial
      rejuvenative procedures, almost always for the forehead, often for the midface
      and less often for the neck. Fat grafting procedures using newly adapted concepts
      are used for the brow, glabella, tear trough deformity, cheeks, lips, chin,
      nasolabial folds, marionette lines, and other areas of soft tissue depressions
      apparent before or after the lifting procedures. This has allowed us to restore
      the tridimensional volume and treat the soft tissue atrophy. Patients with
      significant skeletal soft tissue disproportion due to aging, loss of dentition,
      prior trauma or congenital defects may receive one or more of the following
      implants: glabella, cheek, piriformis, angle of the mandible, mandibular body
      glove type of implant, prejawl implant, chin overlay or a glove type of implant.
      Our preference is for a porous polyethylene material because of its tissue
      ingrowth inductiveness. Individuals who have damaged skin due to solar exposure,
      aging, smoking, etc., may receive Ultrapulse CO2 laser resurfacing at the same
      operative setting (more often) or in a delayed fashion. The Versapulse laser is
      also needed for the treatment of some skin changes secondary to aging such as
      telangiectasias (Variable Pulse Green) and brown spots (Q-Switch 532). The high
      tech facelift has allowed us to treat the severely damaged skin, fat atrophy,
      bone atrophy in many patients, at the same time that the lifting procedure is
      performed. This provides a more comprehensive approach to facial rejuvenation.
      The combination of different techniques and technologies maximizes the
      effectiveness and minimizes the potential side effects of each one. Scars in the
      forehead and scalp are avoided. Incision and fat removal in the lower eyelid are
      often unnecessary. It provides a more precise vertical lifting with correction of
      the tear trough deformity and gives a tridimensional restoration of the facial
      volume. The facial disharmony is treated at every level starting from the facial
      skeletal support to the most external envelope (skin). Over 200 patients have
      been treated this way with a minimal rate of complications. The high-tech facial
      rejuvenation has allowed us to improve the surgical results of our patients
      compared with previous isolated techniques. The combination of each one of the
      techniques require a precise understanding of the limits and benefits of each.
      Case examples of the different combinations will be shown.

PMID- 9767699
TI  - Direct K-wire fixation technique during endoscopic brow lift.
AB  - Endoscopic brow lift has now become a well-established procedure for restoring a
      youthful brow. Multiple techniques have been described for fixation of the scalp;
      however, these methods do not allow for direct positioning of the brow. A simple
      method is described that establishes precise and direct brow fixation using K
      wires. Twelve female patients underwent direct fixation of the brow with one or
      more K-wires to the supraorbital rim. No complications occurred as a result of
      this technique. Direct brow fixation with K-wires appears to be a simple
      effective technique for precise restoration of brow position.

PMID- 9767697
TI  - Body dysmorphic disorder and aesthetic surgery: case report.
AB  - The appearance of psychiatric disorders among plastic surgery patients is well
      known, and its frequency is higher than in other surgical branches. There is
      evidence that these patients may suffer from body dysmorphic disorder (BDD), a
      mental disorder characterized by excessive concern about some imaginary or slight
      physical defect, causing significant clinical discomfort, social deterioration,
      and losses in other important areas of the individuals' activity. We present a
      typical case of BDD and discuss diagnostic criteria and the proper attitude the
      plastic surgeon should adopt toward this kind of patient.

PMID- 9767698
TI  - In favor of the subcutaneous forehead lift using the anterior hairline incision.
AB  - We present our experience with 980 women who had subcutaneous forehead lifts
      using the anterior hairline incision, during the years 1989-1996. The dissection
      is easy and fast; the forehead wrinkles are smoothed by the separation of the
      septa between the frontalis and the skin. The access to the corrugator and the
      procerus muscles is easy, and the adjustment of the brows to the desired location
      can be accurate. We use this approach for 90% of women who are eligible for upper
      face rejuvenation. We have obtained a 96% satisfaction rate; only 1.8% of our
      patients had minor and reversible complications. The scar, which is supposed to
      be the main disadvantage of this procedure, is almost unnoticeable, and none of
      our patients has permanently changed her hairstyle due to this operation. Now,
      during the peak of interest in forehead lifts with limited scars using the
      endoscope, is the time to highlight this time-worn, safe, reproducible, and
      effective approach.

PMID- 9767700
TI  - Blepharoplasty: A classification of selected techniques in the treatment and
      prevention of lower lid margin distortions.
AB  - In the past few years the approach to lower blepharoplasty complications has
      evolved. New and worthy preventive and curative treatments have been suggested
      for both scleral show and ectropion (operations with or without interruption of
      the lid margin, mucosal grafts, orbicularis flaps, etc.). Among these, several
      techniques have been chosen and analyzed, evaluating the advantages and
      disadvantages of each.

PMID- 9767701
TI  - Treatment of orbicularis oculi muscle hypertrophy in lower lid blepharoplasty.
AB  - Treatment of orbicularis oculi muscle hypertrophy during conventional lower
      eyelid blepharoplasty is presented. Horizontal resection of a strip of the
      hypertrophic muscle is carried out, which allows flattening of the muscular bulge
      in an anteroposterior direction. Since no full-thickness vertical reduction is
      performed, this simple procedure is "free" from the risk of "scleral show"
      deformity, due to excessive muscle shortening, leaving a pleasant contour in the
      lower eyelid. The technique has been successfully employed in 27 cases of
      blepharoplasty, with separate skin and muscle flaps.

PMID- 9767702
TI  - One-stage reconstruction of an upper part defect of the auricle.
AB  - A one-stage procedure for the reconstruction of a defect of the upper auricle is
      described. The anterior surface of a carved costal cartilage graft was covered
      with an anterosuperiorly based skin flap, and the posterior surface was covered
      by the superficial mastoid fascial flap and a skin graft. This method can be
      performed easily, without leaving any scar in the hair-bearing area or visible
      postauricular region, and can be applied to cases in which the condition of the
      margin scar of an auricular defect is poor.

PMID- 9767703
TI  - PMMA-Microspheres (Artecoll) for long-lasting correction of wrinkles: refinements
      and statistical results.
AB  - The corium is diminished to about half of its thickness in skin defects and
      wrinkles. All biological materials that increase the thickness of the corium are
      resorbed within a certain time. Therefore, a lasting effect can be achieved only
      with nonresorbable synthetic substances. Artecoll consists of microspheres of 30
      40 microm in diameter, of exceptional surface smoothness, purity, and homogeneity
      related to PMMA. These microspheres are suspended in atelocollagen which serves
      as a vehicle for subdermal implantation. Due to its smooth surface and
      consequential lack of electrical charges, each single microsphere is immediately
      encapsulated with the patient's own collagen fibers, thus preventing dislocation.
      Within 3 months, collagen (making up 75% of Artecoll) is replaced by the body's
      own connective tissue. The microspheres (25% of Artecoll) serve merely as a
      stimulus to the fibroblasts. Indications for Artecoll are all facial folds, lip-
      and philtrum augmentation, chin- and malar augmentation, dark-shadowed eyelids,
      enophthalmos, bony defects in face and hands, nipple reconstruction and
      augmentation, and urinary incontinence. Questionnaires were sent to all patients
      who had received Artecoll in 1993 and 1994. Of a total of 950 questionnaires
      sent, 515 were returned by September 1995. Satisfaction was rated "very good" in
      29%, "good" in 38%, "satisfactory" in 23%, and "no difference" in 8% of the
      patients. The question, "Would you repeat the treatment again?" was answered by
      91% of the patients with "yes." The overall complication rate was 3%. Strictly
      subdermal implantation will prevent longer lasting redness or visibility of the
      Artecoll.

PMID- 9767705
TI  - Innovative new concepts in augmentative breast surgery.
AB  - The female breast is seen as a badge of feminine beauty in our society. While it
      can vary over time and with fashions, the perfect breast will always be
      symmetrically balanced and proportionate to the rest of the body. To create an
      aesthetic and symmetrically balanced breast using implants to enhance them is not
      an easy task. Surgery must combine the concepts of an ideal breast with the
      desires of the patient in terms of size. The satisfactory breast should remain
      soft, well positioned, and mobile to respond to gravity and postural changes. In
      attempting to construct an "ideal breast," certain basic aesthetic anatomical
      proportions should be taken into account: natural positioning of the breast in
      the thorax; symmetry; the position of the nipple-areola complex as the focal
      point of the breast in the frontal view; a side profile of the breast with a
      natural soft fall; and, overall, the position of the new inframammary crease in
      the standing position, while lying down, and while moving.

PMID- 9767704
TI  - Eyebrow asymmetry: ways of correction.
AB  - Ocassionally a patient asks for correction of his asymmetric eyelids. In many
      instances, however, a careful analysis reveals that the actual cause is an
      asymmetry of the eyebrows. Generally, asymmetric eyebrows are due to excessive
      muscle dynamics (i.e., a hyperkinesia of the frontalis or the depressor
      supercilii muscles). Therefore, the asymmetry will not be corrected by an
      asymmetric blepharoplasty, which will instead disclose the preexisting asymmetry,
      much to the concern of the patient. Management of the asymmetric brow is
      demanding and requires a preoperative problem-oriented and detailed analysis of
      the individual patient to achieve satisfactory results. We present 10-years'
      experience using a problem-specific approach. This included intramuscular
      botulinum toxin A injection, superselective neurotomy, endoscopic browlift and
      traditional procedures such as the coronal and direct browlift. Indication,
      patient selection, results, and complications are discussed.

PMID- 9767706
TI  - Technical refinements of infracture for the zygomatic body and arch reduction.
AB  - Nowadays the infracture technique for the zygomatic body and arch has been
      popularized in Oriental countries for the reduction of zygoma. We can obtain
      sufficient operative field to handle the zygoma through the intraoral and
      temporopreauricular incision and control the amount of shaving and infracturing
      zygomatic prominence. We developed three types of infracture technique for the
      reduction of the zygomatic body and arch according to the degree of severity of
      the zygomatic prominence and the shape of the face: Type A, infracturing with
      bone-to-bone contact for mild prominence with/without a long face; Type B,
      infracturing beyond bone-to-bone contact for moderate prominence; and Type C,
      infracturing far beyond bone-to-bone contact and microplate fixation for severe
      prominence with/without a broad and short face. By applying the criteria
      described above, we can obtain aesthetically acceptable results in zygoma
      reduction.

PMID- 9767707
TI  - Xylose transport by the anaerobic thermophile thermoanaerobacter ethanolicus and
      the characterization of a D-xylose-binding protein 
AB  - Thermoanaerobacter ethanolicus is a xylose-utilizing thermophilic anaerobe that
      produces considerable amounts of ethanol. A protein in xylose-growing cells was
      solubilized from cell membranes by extraction with octyl-beta-glucoside. Internal
      peptide sequencing revealed that the protein was the product of a gene, xylF,
      encoding a putative D-xylose-binding protein. Metabolic labeling with 14C
      palmitic acid suggested that this is a lipoprotein that is anchored to the cell
      membrane via a cysteine residue. Binding was highly specific for xylose as
      evident by the lack of competition by sugars with structures similar to xylose.
      The apparent Kd of the protein for xylose was approximately 1.5 &mgr;M, and this
      value was very similar to the affinity constant determined for xylose transport
      by whole cells at low substrate concentrations. Uptake experiments with cells
      also suggested the presence of a separate low-affinity system. Binding activity
      varied less than 20% over a pH range of 4-8, and the level of activity was
      virtually unaffected when temperature was varied between 40 degreesC and 80
      degreesC. This is the first biochemical characterization of a D-xylose-binding
      protein from a thermophilic organism.

PMID- 9767708
TI  - Rhizobacterial glutathione levels as affected by starvation and cadmium exposure.
AB  - The rhizosphere is a continuously fluctuating environment in which severe
      stresses are put on its inhabitants, and glutathione, a reducing tripeptide, and
      related compounds probably have important roles in cellular protection. In the
      present study the metabolism of glutathione was examined in rhizobacteria
      subjected to stress. The plant-growth-promoting rhizobacterium Pseudomonas
      fluorescens 5.014 and its mutant 5-2/4 were exposed to starvation, either by
      resuspension or exhaustion, and to cadmium. Glutathione levels, cell protein, and
      viable count were determined and compared in different conditions. Both
      starvation and cadmium exposure decreased the amount of glutathione in the cell.
      No changes of the glutathione concentration in the medium were observed with or
      without the presence of rhizobacteria, indicating that there was no transport
      over the cell membrane. The glutathione levels within the rhizobacteria may give
      valuable information on how different stresses affect the bacteria. In this
      study, the involvement of glutathione in the increased stress resistance earlier
      observed in nutrient-starved P. fluorescens was not supported. The concentration
      of bacterial glutathione is suggested as a possible marker for rhizosphere
      competence, which, however, needs to be further evaluated with several strains of
      rhizobacteria.

PMID- 9767709
TI  - Nickel uptake by Pseudomonas aeruginosa: role of modifying factors.
AB  - Pseudomonas aeruginosa cells growing in minimal medium were 40-fold more
      sensitive to Ni2+ than cells growing in enriched medium, suggesting a possible
      protective role of medium ingredients. Likewise, cells pre-grown in enriched
      medium showed a high Km (6.15 mM) and increased Ni2+ uptake (950 nmol mg-1
      protein, 1h) over cells pre-sown in minimal medium (Km, 0.48 mM; 146 nmol mg-1
      protein, 1 h). The overall pattern indicates that cells pre-grown in enriched
      medium were characterized by having lowered affinity towards Ni2+ than those with
      minimal medium background. The enhanced Ni2+ uptake by enriched medium-grown
      cells can be correlated with the improved metabolic state of the cells. Ni2+
      uptake was optimum at neutrality (pH 7.0). A major Ni2+ transport system was
      competitively inhibited by Mg2+, Zn2+, Cd2+, or Co2+ (400 microM each).
      Noticeably, a minor Ni2+ transport pathway was still operative even in the higher
      concentration range of Mg2+ (4 mM and 40 mM). The stimulation of Ni2+ uptake
      monitored in the presence of different carbon sources (0.5% wt/vol, each) showed
      the sequence: glucose (1.6-fold) > phenol = gallic acid (1.5-fold). Succinate, in
      comparison, reduced Ni2+ uptake (0.5-fold) possibly because of its acting as a
      metal chelator as well. Sensitivity of Ni2+ transport towards methyl viologen,
      azide, 2-4 DNP, and DCCD suggested that transport was energy-linked.

PMID- 9767711
TI  - Lateral and perpendicular interaction forces involved in mobile and immobile
      adhesion of microorganisms on model solid surfaces.
AB  - Gliding and near-surface swimming of microorganisms are described as a mobile
      form of microbial adhesion that need not necessarily be reversible. It is argued
      that the reversibility of microbial adhesion depends on the depth of the
      secondary interaction minimum, calculated from the forces between an organism and
      a substratum acting in a direction perpendicular to the substratum surface. The
      mobility of adhering microorganisms depends on lateral interactions between the
      organisms. On ideally homogeneous and smooth model surfaces, only mobile adhesion
      occurs because the multibody, lateral interactions are weak compared with the
      thermal or Brownian motion energy of the organisms. Minor chemical or structural
      heterogeneities, which exist on all real-life surfaces, yield a lateral
      interaction on adhering microorganisms. This causes their immobilization, which
      helps to explain the physicochemical nature of microbial gliding or near-surface
      swimming. Moreover, these lateral interaction energies are one order of magnitude
      smaller than the Lifshitz-Van der Waals, electrostatic, and acid-base forces
      acting perpendicular to substratum surfaces that are responsible for adhesion.

PMID- 9767710
TI  - Characterization of the genes encoding the botulinum neurotoxin complex in a
      strain of Clostridium botulinum producing type B and F neurotoxins.
AB  - The organization of the clusters of genes encoding proteins of the botulinum
      neurotoxin (BoNT) progenitor complex was elucidated in a strain of Clostridium
      botulinum producing type B and F neurotoxins. With PCR and sequencing strategies,
      the type B BoNT-gene cluster was found to be composed of genes encoding BoNT/B,
      nontoxic nonhemagglutinin component (NTNH), P-21, and the hemagglutinins HA-33,
      HA-17, and HA-70, whereas the type F BoNT-gene cluster has genes encoding BoNT/F,
      NTNH, P-47, and P-21. Comparative sequence analysis showed that BoNT/F in type BF
      strain 3281 shares highest homology with BoNT/F of non-proteolytic (group II) C.
      botulinum whereas NTNH and P-21 in the type F cluster of strain 3281 are more
      similar to the corresponding proteins in proteolytic (group I) type F C.
      botulinum. These findings indicate diverse evolutionary origins for genes
      encoding BoNT/F and its associated non-toxic proteins, although the genes are
      contiguous. By contrast, sequence comparisons indicate that genes encoding BoNT/B
      and associated non-toxic proteins in strain 3281 possess a similar evolutionary
      origin. It was demonstrated that the genes present in the BoNT/B gene cluster of
      this type BF strain show exceptionally high homology with the equivalent genes in
      the silent BoNT/B gene cluster of C. botulinum type A(B), possibly indicating
      their common ancestry.

PMID- 9767712
TI  - Protection of mice against challenge with homologous and heterologous serovars of
      Actinobacillus pleuropneumoniae after live vaccination.
AB  - Protective immune responses and the virulence of Actinobacillus pleuropneumoniae
      (APP) have been attributed, in part, to toxins (Apx) produced by the bacterium. A
      mutant of the serovar 7 strain HS93 (HS93Tox-), lacking the genes encoding the
      structural toxin ApxA and the post-translational activating protein ApxC, but
      retaining the genes required for secretion ApxB and ApxD, was isolated and shown
      to be attenuated in a mouse model. A plasmid vector system was developed and used
      to express the ApxA gene from within the HS93Tox- strain. The resulting strain,
      HS93Tox-/pIG-T1K, expresses the Apx structural protein in a non-activated form.
      HS93Tox-/pIG-T1K was shown to be attenuated in a mouse model and to be capable of
      inducing Apx-specific antibodies, which were boosted on re-inoculation. Live
      vaccination of mice with HS93Tox-/pIG-T1K offered protection against homologous
      wild-type serovar 7 challenge, and also heterologous challenge with a serovar 1
      strain. This is in contrast to vaccination with the HS93Tox- strain, which failed
      to protect mice against a heterologous challenge.

PMID- 9767714
TI  - Effect of carbon source on production of alpha-L-arabinofuranosidase by
      aureobasidium pullulans 
AB  - A color-variant strain of Aureobasidium pullulans (NRRL Y-12974) produced alpha-L
      arabinofuranosidase (alpha-L-AFase) when grown in liquid culture on sugar beet
      arabinan, wheat arabinoxylan, L-arabinose, L-arabitol, xylose, xylitol, oat spelt
      xylan, corn fiber, or arabinogalactan. L-Arabinose was most effective for
      production of both whole-broth and extracellular alpha-L-AFase activity, followed
      by L-arabitol. Oat spelt xylan, sugar beet arabinan, xylose, xylitol, and wheat
      arabinoxylan were intermediate in their ability to support alpha-L-AFase
      production. Lower amounts of enzyme activity were detected in corn fiber- and
      arabinogalactan-grown cultures.

PMID- 9767713
TI  - Conservation of the major cold shock protein in lactic acid bacteria.
AB  - Primers designed from consensus regions of the major cold shock gene of different
      bacterial species were used in PCR amplification of Lactic Acid Bacteria (LAB).
      An appropriately-sized PCR product was obtained from Lactococcus lactis subsp.
      lactis LL43-1 and MG1363; Lactococcus lactis subsp. cremoris LC10-1, LC11-1, and
      LC12-1; Streptococcus thermophilus ST1-1; Enterococcus faecalis EF1-1;
      Lactobacillus acidophilus LA1-1; Lactobacillus helveticus LH1-1; Pediococcus
      pentosaceus PP1-1; and Bifidobacterium animalis BA1-1. The PCR products were
      cloned and sequenced. The deduced amino acid sequences displayed high sequence
      similarity with the major cold shock proteins of Escherichia coli and Bacillus
      subtilis and the human Y-box factor. The amino acid residues of the cold shock
      domain implicated in nucleic acid binding in several unrelated species were also
      highly conserved in the LAB strains. It is possible, therefore, that this protein
      in LAB may also act as a transcriptional enhancer to other cold shock genes
      and/or act as an RNA chaperone unwinding tightly folded RNA molecules.

PMID- 9767715
TI  - A genomically modified marker strain of Escherichia coli.
AB  - Contamination of the environment with human sewage represents a serious public
      health concern in which Escherichia coli plays a central role, either directly as
      a human pathogen or indirectly through its use as an indicator organism. There is
      thus an ongoing effort to better understand the behavior of E. coli within such
      environments. Useful to such studies is the ability to readily detect a specific
      E. coli population and distinguish it from similar indigenous bacteria. Herein,
      we report the construction of an E. coli strain (PCPHR) that expresses a Stable
      Artificial RNA (SAR) from the chromosomal rrnH operon. The SAR product is present
      in large numbers of copies/cell and thus provides an enhanced detection signal
      without significant effect on the wild-type growth rate. Detection can be
      accomplished by any of several routine molecular methods. Preliminary studies
      suggest SAR expression levels correlate positively with growth. PCPHR is
      immediately available for use as a marker strain for E. coli in application in
      the arena of public health or environmental studies.

PMID- 9767717
TI  - Plasmid-mediated gene transfer between insect-resident bacteria, Enterobacter
      cloacae, and plant-epiphytic bacteria, Erwinia herbicola, in guts of silkworm
      larvae.
AB  - Five strains of Enterobacter cloacae isolated from several species of plants and
      insects were able to grow in the guts of silkworm larvae. A much larger
      population of Ent. cloacae strains was detected in the insect guts and feces
      collected 3 and 6 days than in samples collected 1 day after feeding artificial
      diets contaminating these bacteria. Furthermore, insect-origin strains of Ent.
      cloacae were mated with a donor strain, epiphytic Erwinia herbicola, harboring
      RSF1010 and pBPW1::Tn7 plasmids in the insect guts by introducing these bacteria
      through separate artificial diets administered at different times. A number of
      transconjugants, Ent. cloacae strains which had acquired RSF1010 plasmid, were
      detected from guts and fecal samples at transfer frequencies of 10(-2) to 10(-3)
      per recipient. Thus, gene transfer between epiphytic Er. herbicola and insect
      resident Ent. cloacae strains in the insect guts was confirmed. These findings
      may provide significant information about the role of "in insecta mating" in the
      evolution of these bacteria.

PMID- 9767716
TI  - Transfer and expression of a multiple antibiotic resistance plasmid in marine
      bacteria.
AB  - Conjugal transfer of a multiresistance plasmid from Pseudomonas fluorescens to
      halophilic and halotolerant bacteria was studied under in vitro and in situ
      conditions. Mating conducted in broth as well as on plates yielded a plasmid
      transfer frequency of as high as 10(-3). Among these two, plate mating
      facilitated conjugal transfer of plasmid, because the cell-to-cell contact is
      more in plate mating. When P. fluorescens was incubated in seawater, the organism
      progressively lost its colony forming activity within 15 days. Microscopic
      examination revealed the presence of very short rods, indicating that the cells
      have become viable but nonculturable (VNC). Mating conducted in natural seawater
      without any added nutrients revealed that the conjugal transfer is influenced by
      the physical state of the donor and the recipients as well as the availability of
      nutrients. But a plasmid transfer frequency of 10(-7) was obtained even after the
      donor cells have become VNC suggesting that the nonculturable state and nutrient
      deprived condition may not limit plasmid transfer. The results suggest that the
      terrestrial bacteria entering into the seawaters with antibiotic resistance
      plasmids may be responsible for the prevalence of resistance genes in the marine
      environment.

PMID- 9767718
TI  - Buchnera aphidicola (Aphid endosymbiont) contains genes encoding enzymes of
      histidine biosynthesis.
AB  - Buchnera aphidicola is an endosymbiont of aphids. One of its functions appears to
      be the synthesis of essential amino acids for the aphid host. A 12.8-kilobase B.
      aphidicola DNA fragment has been cloned and sequenced. It contains genes encoding
      all of the enzymes required for the biosynthesis of the essential amino acid
      histidine. The order of the genes, hisGDCBHAFI, is the same as that found in
      Escherichia coli and is consistent with their constituting a single transcription
      unit. The DNA fragment also contained genes involved in aromatic amino acid
      biosynthesis (aroC), the oxidative pentose pathway (gnd), and 2'
      deoxyribonucleotide metabolism (dcd), as well as a tRNA synthase (metG).

PMID- 9767719
TI  - Isolation of adenylate cyclase gene-specific sequences from Ophiostoma novo-ulmi,
      Candida albicans, and Agaricus bisporus by PCR.
AB  - Degenerate primers corresponding to consensus sequences in the catalytic domains
      of known fungal adenylate cyclases were used to isolate gene-specific homologs
      from the Dutch elm disease pathogen Ophiostoma novo-ulmi, the dimorphic human
      pathogen Candida albicans, and the commercial mushroom Agaricus bisporus. All
      three fungi gave the expected PCR product of about 390 bp. Computer searches of
      the databases revealed that the products generated from O. novo-ulmi and C.
      albicans were highly similar to the adenylate cyclase gene of Magnaporthe grisea,
      the rice blast fungus (91% and 79%, respectively). The PCR product from the
      homobasidiomycete A. bisporus, on the other hand, showed 78% similarity to the
      uac1 gene of the heterobasidiomycete smut fungus, Ustilago maydis. Southern
      hybridization indicated that all three fungi contain a single adenylate cyclase
      gene. Our data suggest that PCR will be highly successful for the isolation of
      adenylate cyclase sequences from other fungi.

PMID- 9767721
TI  - Impact of family physicians on mammography screening.

PMID- 9767720
TI  - Vaccinations in adults: missed opportunities.

PMID- 9767722
TI  - Measles, mumps, rubella vaccine and allergy to egg.

PMID- 9767723
TI  - Tibiofibular diastasis in the injured ankle.

PMID- 9767724
TI  - Recognizing neoplastic skin lesions: a photo guide.
AB  - Malignant lesions of the skin are common. Patients who develop squamous cell
      carcinoma and malignant melanoma often have recognizable precursor conditions. A
      few skin lesions resemble malignancies. Lesions that are growing, spreading or
      pigmented, or those that occur on exposed areas of skin are of particular
      concern. Knowing the similarities and differences between these lesions allows
      the primary physician to make a diagnosis in most cases by simple inspection and
      palpation. When in doubt, it is appropriate to perform an excisional biopsy of
      small lesions or punch biopsy of larger lesions. Removal of premalignant lesions
      will reduce the occurrence of malignant disease. Almost all skin cancers can be
      cured by early excision or destruction. For these reasons, physicians should be
      aware of the risk factors for skin cancer, educate patients about risk reduction
      and include skin inspection for premalignant and malignant lesions as a part of
      routine health maintenance examinations.

PMID- 9767725
TI  - The Gomco circumcision: common problems and solutions.
AB  - Circumcision performed using the Gomco clamp is usually quick and effective, and
      results in very little bleeding. However, every clinician performing circumcision
      occasionally has concerns or questions regarding the procedure. Some of the more
      common concerns regarding the use of the Gomco clamp are technique-related,
      including choosing the correct size of the Gomco bell and clamp for the
      procedure, choosing the right method of getting the foreskin properly through the
      hole of the Gomco base plate, and assessing how much foreskin to remove. Other
      concerns include poor cosmetic results, contraindications to routine
      circumcision, and circumcision in an infant whose mother has human
      immunodeficiency virus. This article reviews the technique of circumcision using
      the Gomco clamp and answers some of the more common questions.

PMID- 9767727
TI  - Management of female sexual assault.
AB  - A sexual assault occurs once every 6.4 minutes in the United States. One in every
      six women will be raped during her lifetime. Although a woman is four times more
      likely to be assaulted by someone she knows than by someone she does not know,
      the majority of these crimes go unreported even though rape is a felony. The
      purpose of the medical examination after a sexual assault is to assess the
      patient for physical injuries and to collect evidence for forensic evaluation and
      possible legal proceedings. Laboratory samples should be obtained at the initial
      visit and should include testing for pregnancy, syphilis, hepatitis B and human
      immunodeficiency virus infection. Treatment should address physical injuries,
      pregnancy prophylaxis, sexually transmitted diseases and psychosocial sequelae.
      Appropriate referral services should be initiated during the initial visit.
      Victims of sexual assault require appropriate care, follow-up and information
      regarding their legal rights. Family physicians should be familiar with the state
      laws governing collection of evidence and should be prepared to advise the
      patient to report the crime. The history should be confined to medically relevant
      facts and should be conducted in a safe and quiet environment.

PMID- 9767726
TI  - Constipation in the elderly.
AB  - Constipation affects as many as 26 percent of elderly men and 34 percent of
      elderly women and is a problem that has been related to diminished perception of
      quality of life. Constipation may be the sign of a serious problem such as a mass
      lesion, the manifestation of a systemic disorder such as hypothyroidism or a side
      effect of medications such as narcotic analgesics. The patient with constipation
      should be questioned about fluid and food intake, medications, supplements and
      homeopathic remedies. The physical examination may reveal local masses or
      thrombosed hemorrhoids, which may be contributing to the constipation. Visual
      inspection of the colon is useful when no obvious cause of constipation can be
      determined. Treatment should address the underlying abnormality. The chronic use
      of certain treatments, such as laxatives, should be avoided. First-line therapy
      should include bowel retraining, increased dietary fiber and fluid intake, and
      exercise when possible. Laxatives, stool softeners and nonabsorbable solutions
      may be needed in some patients with chronic constipation.

PMID- 9767728
TI  - Recognizing occupational disease--taking an effective occupational history.
AB  - Occupational exposures contribute to the morbidity and mortality of many
      diseases. However, occupational diseases continue to be underrecognized even
      though they are responsible for an estimated 860,000 illnesses and 60,300 deaths
      each year. Family physicians can play an important role in improving the
      recognition of occupational disease, preventing progressive illness and
      disability in their own patients, and contributing to the protection of other
      workers similarly exposed. This role can be maximized if physicians raise their
      level of suspicion for workplace disease, develop skills in taking occupational
      histories and establish routine access to occupational health resources.

PMID- 9767730
TI  - Keeping abreast of new drug approvals and labeling changes.

PMID- 9767729
TI  - Short-term tuberculosis prophylaxis is effective in persons with HIV.

PMID- 9767731
TI  - AAP issues policy statement on parental discipline of children.

PMID- 9767732
TI  - ACOG releases report on risk factors, causes and management of postpartum
      hemorrhage.

PMID- 9767733
TI  - The value of dose intensification of standard chemotherapy for advanced breast
      cancer using colony-stimulating factors alone.

PMID- 9767734
TI  - Sentinel node biopsy: a revolution in the surgical management of breast cancer?

PMID- 9767737
TI  - The status of transfusion medicine science and the role of the American
      Association of Blood Banks: the journey continues.

PMID- 9767735
TI  - The development of combination therapy involving camptothecins: a review of
      preclinical and early clinical studies.

PMID- 9767736
TI  - Hormonal therapy of breast cancer.

PMID- 9767738
TI  - Interagency Genome Amplification Testing Task Force: preliminary report.

PMID- 9767739
TI  - Mini-pool screening by nucleic acid testing for hepatitis B virus, hepatitis C
      virus, and HIV: preliminary results.
AB  - BACKGROUND: The purpose of this study was to evaluate the feasibility of nucleic
      acid testing (NAT) of mini-pools as a blood donation screening test. STUDY DESIGN
      AND METHODS: The stepwise implementation of NAT of mini-pools began in January
      1997. Since March 1997, all blood donations collected by the German Red Cross
      Blood Transfusion Service of Baden-Wurttemberg were tested for hepatitis B virus
      (HBV), hepatitis C virus (HCV), and HIV nucleic acids. An extra barcoded serum
      sample is collected from each blood donor for NAT-based screening, which is
      performed only on hepatitis B surface antigen-, anti-HCV-, anti-HIV-, and anti
      Treponema pallidum-seronegative donations. Samples are pooled to a maximum of 96.
      Positive results are resolved through intersecting subpools (a chessboard
      design). NAT-based screening does not include a virus concentration step before
      nucleic acid extraction. RESULTS: By the end of October 1997, 331, 783 donations
      in 3,779 pools had been screened. As yet, no viremic but seronegative blood donor
      has been found for the three markers. CONCLUSION: It is feasible to incorporate
      NAT-based screening of mini-pools into the routine virus diagnostics of a large
      blood transfusion service. It remains to be determined whether screening blood
      donations by NAT will indeed increase the safety of blood supply.

PMID- 9767740
TI  - The use of polymerase chain reaction in plasma pools for the concomitant
      detection of hepatitis C virus and HIV type 1 RNA.
AB  - BACKGROUND: Detection of viral nucleic acids might increase blood transfusion
      safety through the detection of recently infected blood donors during the
      preseroconversion window period. Individual screening is difficult to apply,
      because of technical and financial constraints. STUDY DESIGN AND METHODS: A
      polymerase chain reaction (PCR)-based assay including a polyethylene glycol
      precipitation step was developed for the concomitant detection of hepatitis C
      virus (HCV) and HIV type 1 (HIV-1) RNA in plasma pools corresponding to 50 blood
      donations by the use of commercial assays. RESULTS: The assay had a sensitivity
      of less than 33 copies per mL for HCV RNA and 1000 copies per mL for HIV-1 RNA
      for each individual sample included in the pool. The eight preseroconversion
      samples with HCV RNA between 1,250 and 762,000 copies per mL were all detected
      when 100-microL aliquots from the samples were introduced into 5-mL pools of 50
      blood donations. CONCLUSIONS: A PCR-based pooling assay associating a
      prepurification step with polyethylene glycol allows for the screening of blood
      donations for HCV and HIV-1 RNA without marked loss of sensitivity from that seen
      with commercially available assays. This procedure might increase blood safety
      through systematic screening of blood donations at relatively low cost.

PMID- 9767741
TI  - Screening blood donations for viral genomes: multicenter study of real-time
      simulation using pooled samples on the model of hepatitis C virus RNA detection.
AB  - BACKGROUND: The systematic screening for several blood-borne viral genomes in
      blood donations is a complementary safety measure planned or discussed by the
      national authorities of several countries. STUDY DESIGN AND METHODS: To
      appreciate the feasibility of such screening using pooled samples, a multicenter
      study of real-time simulation has been performed on the model of hepatitis C
      virus (HCV) infection. Four blood transfusion center laboratories and two
      research and diagnosis laboratories simultaneously screened, by several HCV RNA
      polymerase chain reaction assays, a panel of plasma sample pools of different
      sizes (500, 100, and 10 samples), collected from HCV-infected or HCV-uninfected
      blood donors. One viremic plasma was introduced in each pool. HCV RNA was
      detected by in-house polymerase chain reaction procedures or by standardized
      manual or semi-automated polymerase chain reaction assays. RESULTS: The results
      indicate the feasibility of sample pooling, which renders the screening for viral
      genomes by molecular biology techniques applicable in the short term and the
      importance of the experience of laboratory personnel in the use of molecular
      biology tools. CONCLUSION: The improvement of standardized assays needs to be
      continued, and training of laboratory staff members appears to be a crucial step
      before systematic screening of blood donations for viral genomes by molecular
      biology techniques can occur.

PMID- 9767742
TI  - Perioperative myocardial ischemic episodes are related to hematocrit level in
      patients undergoing radical prostatectomy.
AB  - BACKGROUND: The anemia associated with perioperative blood conservation has
      raised concerns regarding the safety of these strategies in patients with
      ischemic cardiovascular disease. Therefore the relationship between hematocrit
      level and myocardial ischemic episodes in a group of elderly patients undergoing
      elective noncardiac surgery was studied. STUDY DESIGN AND METHODS: One hundred
      ninety patients undergoing radical prostatectomy were randomly assigned to one of
      three blood conservation groups: preoperative autologous blood donation, acute
      normovolemic hemodilution, and preoperative erythropoietin therapy with acute
      normovolemic hemodilution. Patients underwent ambulatory electrocardiography
      monitoring to evaluate for myocardial ischemia at randomization (baseline), 7
      days preoperatively, throughout surgery, and for 24 hours after surgery. RESULTS:
      Myocardial ischemic episodes occurred in 61 (34%) of 181 evaluable patients.
      Patients with hematocrit levels < 28 percent immediately after surgery were
      significantly (p = 0.05) more likely to have intraoperative and postoperative ECG
      ischemic episodes. Intraoperative ischemia and tachycardia correlated (r = 0.21,
      p = 0.008) with hematocrit levels. Hematocrit levels after surgery were
      associated with postoperative ischemia (r = 0.14, p = 0.03) and duration of
      myocardial ischemic episodes (r = 0.14, p = 0.04). After adjusting for other risk
      factors, intraoperative tachycardia episodes, hematocrit level < 28 percent
      immediately after surgery, and risk factors for coronary artery disease were
      independently associated with the likelihood of intraoperative ischemia (r =
      0.36, p = 0.002, area under receiver operating characteristic curve = 0.73).
      Similarly, tachycardia episodes and hematocrit levels < 28 percent immediately
      after surgery were independently associated with ischemic episodes during the
      first postoperative day (r = 0.30, p = 0.004, area under receiver operating
      characteristic curve = 0.71). CONCLUSION: A hematocrit level < 28 percent is
      independently associated with risk for myocardial ischemia during and after
      noncardiac surgery. Avoidance of cardiac complications may require higher
      transfusion thresholds, closer attention to tachycardia, or better monitoring for
      ischemia.

PMID- 9767743
TI  - Prospective validation of a point score system for predicting blood transfusion
      following hip or knee replacement.
AB  - BACKGROUND: The purpose of this study was to validate a previously published
      point score system for predicting the likelihood of a postoperative blood
      transfusion following hip or knee replacement. STUDY DESIGN AND METHODS: Data
      were collected prospectively on 460 sequential patients undergoing elective hip
      and knee replacement at two academic hospitals. Blood transfusion frequency was
      determined for patients in each of the four risk strata, as defined by the point
      score system. The accuracy of the system was validated by calculating the area
      under the receiver operating characteristic (ROC) curve for each site. Data were
      then combined and inappropriate blood transfusions were eliminated, by using the
      American College of Physicians guidelines. The frequencies of blood transfusion
      within each strata were recalculated along with an ROC curve. RESULTS: The point
      score system accurately predicted the likelihood of blood transfusion at both
      hospitals, despite marked differences in overall transfusion frequencies. The
      calculated areas under the ROC curves were 0.78 and 0.79 for the two sites. The
      point score system also proved valid when only appropriate blood transfusions
      were considered, with a calculated area under the ROC curve of 0.74. CONCLUSION:
      The point score system can accurately predict the likelihood of postoperative
      blood transfusion following hip or knee replacement. Such a system can be used to
      target high-risk patients for preoperative autologous blood donation.

PMID- 9767744
TI  - Frequency of immediate adverse effects associated with apheresis donation.
AB  - BACKGROUND: Apheresis donation is considered safe, but the incidence of adverse
      effects has not been determined in a large multicenter series of donations with
      modern instruments. STUDY DESIGN AND METHODS: The Hemapheresis Committee of the
      American Association of Blood Banks devised a uniform questionnaire that asked
      about 32 specific adverse effects. Transient paresthesia and mild vasovagal
      events were excluded. A survey was conducted in 1995; 17 centers returned 19,611
      responses concerning 250 to 2,000 consecutive apheresis donations per center.
      RESULTS: Six hundred adverse effects were reported in 428 donations (2.18% of
      donations). Pain or hematoma at a venipuncture site was the most common response
      (1.15% of donations); only 203 donations had other (nonvenipuncture) adverse
      effects (1.04%). Total and nonvenipuncture rates were, respectively, 4.84 and
      2.92 percent for 2,295 first donations and 1.78 and 0.77 percent for 17,303
      repeat donations (p < 0.001). Rates of nonvenipuncture symptoms in first and
      repeat donations were, respectively, citrate-induced nausea and/or vomiting, 0.87
      and 0.27 percent; tetany, 0.09 and 0.04 percent; pallor and/or diaphoresis, 1.87
      and 0.32 percent; vasovagal nausea and/or vomiting, 0.87 and 0.13 percent;
      syncope and/or seizure, 0.39 and 0.04 percent; and chills and/or rigors, 0.31 and
      0.01 percent. The overall rate of donor unconsciousness was 0.08 percent.
      Hemolysis was reported twice. Clotting or leakage occurred in 0.08 percent of
      donations, and inability to return blood occurred in 0.16 percent. No life
      threatening adverse effects were reported. Procedure-specific nonvenipuncture
      rates were 1.05 percent of 17,584 platelet donations, 0.67 percent of 594 white
      cell donations, and 0.37 percent of 1,354 plasma donations. Center-specific rates
      varied from 0.32 to 6.81 percent of donations for total adverse effects and from
      0.11 to 2.92 percent of donations for nonvenipuncture events. CONCLUSION:
      Apheresis donation is a safe undertaking, suitable for voluntary blood donors,
      with a very low risk of serious adverse effects. The risk of unconsciousness is
      lower than that found in many studies of whole-blood donation.

PMID- 9767745
TI  - Intra-apheresis recruitment of blood progenitor cells in children.
AB  - BACKGROUND: Determination of the optimal duration of apheresis requires a careful
      examination of blood progenitor cell (BPC) kinetics during apheresis. Intra
      apheresis recruitment of BPCs should be evaluated. STUDY DESIGN AND METHODS:
      Twenty-six apheresis procedures were performed in 13 children with various
      malignant disorders (ages, 10 months to 17 years; median, 7 years) to collect
      BPCs for autologous transplant, using a blood cell separator with 2 to 5.2 blood
      volumes processed. The subjects were divided into three groups according to age:
      below 1 year (n = 4), 2 to 10 years (n = 5), and 11 to 20 years (n = 4). BPCs
      were mobilized by a combination of chemotherapy and granulocyte-colony
      stimulating factor (G-CSF; 2-7.5 micrograms/kg/day intravenous drip). The levels
      of circulating CD34+ cells and colony-forming units-granulocyte-macrophage (CFU
      GM) were monitored to examine intra-apheresis recruitment. For every 50 mL per kg
      or 2 L of processed blood, 5-mL blood samples were collected via a central line.
      RESULTS: In the first apheresis procedure, more CD34+ cells were mobilized by the
      procedure itself in the infant group than in the older groups, and the number of
      cells decreased with the subject's age. When the same analysis was made during
      the second apheresis procedure, performed 1 day later, the levels of both CD34+
      cells and CFU-GM had decreased to below the preapheresis values in all of the
      populations. Cell yields in the second apheresis procedure were significantly
      lower than those in the first. CONCLUSION: Although several factors prevent a
      reliable analysis, the data suggest that the intra-apheresis recruitment of BPCs
      may be age-specific; the continuous and prolonged supply of cells from the bone
      marrow to peripheral blood that occurs during apheresis is more predominant in
      infants, which leads to the collection of proportionately more BPCs in younger
      children than in their older counterparts.

PMID- 9767747
TI  - Evaluation of a new automated instrument for pretransfusion testing.
AB  - BACKGROUND: A number of automated devices for pretransfusion testing have
      recently become available. This study evaluated a fully automated device based on
      column agglutination technology (AutoVue System, Ortho, Raritan, NJ). STUDY
      DESIGN AND METHODS: Some 6747 tests including forward and reverse ABO group, Rh
      type and phenotype, antibody screen, autocontrol, and crossmatch were performed
      on random samples from 1069 blood donors, 2063 patients, and 98 newborns and cord
      blood. Also tested were samples from 168 immunized patients and 53 donors
      expressing weak or variant A and D antigens. Test results and technician times
      required for their performance were compared with those obtained by standard
      methods (manual column agglutination technology, slide, semiautomatic handler).
      RESULTS: No erroneous conclusions were found in regard to the 5028 ABO group and
      Rh type or phenotype determinations carried out with the device. The device
      rejected 1.53 percent of tests for sample inadequacy. Of the remaining 18 tests
      with discrepant results found with the device and not confirmed with the standard
      methods, 6 gave such results because of mixed-field reactions, 10 gave negative
      results with A2 RBCs in reverse ABO grouping, and 2 gave very weak positive
      reactions in antibody screening and crossmatching. In the samples from immunized
      patients, the device missed one weak anti-K, whereas standard methods missed five
      weak antibodies. In addition, 48, 34, and 31 of the 53 weak or variant antigens
      were detected by the device, the slide method, and the semiautomated handler,
      respectively. Technician time with the standard methods was 1.6 to 7 times higher
      than that with the device. CONCLUSION: The technical performance of the device
      compared favorably with that of standard methods, with a number of advantages,
      including in particular the saving of technician time. Sample inadequacy was the
      most common cause of discrepancy, which suggests that standardization of sample
      collection can further improve the performance of the device.

PMID- 9767746
TI  - The VS and V blood group polymorphisms in Africans: a serologic and molecular
      analysis.
AB  - BACKGROUND: VS and V are common red cell antigens in persons of African origin.
      The molecular background of these Rh system antigens is poorly understood. STUDY
      DESIGN AND METHODS: Red cells from 100 black South Africans and 43 black persons
      from Amsterdam, the Netherlands, were typed serologically for various Rh system
      antigens. Allele-specific polymerase chain reaction and sequencing of polymerase
      chain reaction products were used to analyze C733G (Leu245Val) and G1006T
      (Gly336Cys) polymorphisms in exons 5 and 7 of RHCE and the presence of a D-CE
      hybrid exon 3. RESULTS: The respective frequencies of all VS+ and of VS+ V-(r's)
      phenotypes were 43 percent and 9 percent in the South Africans and 49 percent and
      12 percent in the Dutch donors. All VS+ donors had G733 (Val245), but six with
      G733 were VS- (4 V+w, 2 V-). The four VS- V+w donors with G733 appeared to have a
      CE-D hybrid exon 5. T1006 (Cys336) was present in 12 percent and 16 percent of
      donors from the two populations. With only a few exceptions, T1006, a D-CE hybrid
      exon 3, and a C410T (Ala137Val) substitution were associated with a VS+ V
      phenotype ((C)ces or r's haplotype). Two VS+ V-individuals, with the probable
      genotype, (C)ces/(C)ces), were homozygous for G733 and for T1006. CONCLUSIONS: It
      is likely that anti-VS and anti-V recognize the conformational changes created by
      Val245, but that anti-V is sensitive to additional conformational changes created
      by Cys336.

PMID- 9767748
TI  - Clinical trial and local process evaluation of an apheresis system for
      preparation of white cell-reduced platelet components.
AB  - BACKGROUND: A new method for the consistent preparation of white cell (WBC)
      reduced plateletpheresis components, the Spectra Leukoreduction System (LRS), was
      evaluated by clinical trial and local process validation. The centrifuge-based
      system was projected to decrease the WBC content of plateletpheresis components
      to a level below 1 x 10(6) per unit. Phase I and II clinical trials were
      performed. The manufacturer's claims were then tested at the local level with an
      ongoing quality assurance program. STUDY DESIGN AND METHODS: In Phase I, a cross
      over analysis of five subjects compared LRS to standard plateletpheresis
      procedures in collection efficiency and component quality: a panel of in vitro
      measures was taken on Day 0 and Day 5. In Phase II, the LRS process was tested on
      a larger scale (n = 57; control = 58) with component transfusion. Finally,
      validation, determination of degree of conformance with standards, and ongoing
      quality control were performed locally on a newly installed instrument. RESULTS:
      Phase I and II trials revealed no significant differences between LRS and control
      units in donor or recipient safety and comfort, platelet function and yield, or
      component volume. WBC per-unit values were significantly different: the LRS
      median per unit was 3.2 x 10(4) WBCs, versus 81.4 x 10(4) for control units.
      Assessment of process capability gave an estimate of 99-percent confidence that
      99.5 percent of LRS units would be WBC reduced to < 1 x 10(6) WBCs. Local process
      validation and quality control revealed 90-percent confidence that 99 percent of
      the units would be WBC reduced and 99.9-percent confidence that 75 percent would
      exceed platelet yield standards; the process was stable over time. CONCLUSIONS:
      The LRS is safe for apheresis and the component produced is safe for transfusion
      with platelet function and yield equivalent to controls and WBC reduction
      superior to controls. Local process evaluation confirmed that component quality
      meets the goals of the institution.

PMID- 9767749
TI  - The histo-blood group ABO system and tissue transplantation.
AB  - In general, one might expect that ABO incompatibility of donor and recipient
      would be important to some degree if viability of the transplanted allograft is
      important for graft incorporation and function. This is true for some recipients
      of organs. However, ABO incompatibility appears to play a minor role, if any, in
      the clinical success of viable cornea and viable skin allografts. Even though A
      and B antigens may be present on the transplanted tissue, other factors that can
      contribute include the strength of the immune response, the avidity of the
      antibody, and the dose of the antigen presented, which may vary from donor to
      donor. Although A and B antigens are present on endothelium, the use of ABO
      incompatible heart valves is successful, as they carry out their mechanical
      function by using the strength of the connective tissue rather than the viability
      of the donor endothelium. The presence, immunogenicity, and significance of A and
      B antigens in human vessel transplants have not been well studied. With the more
      commonly transplanted tissue, such as bone and tendon, posttransplant success
      does not depend on cellular viability or ABO compatibility.

PMID- 9767750
TI  - Contribution of nucleic acid amplification techniques to the safety of blood
      components in France.

PMID- 9767751
TI  - Lipid priming agents and transfusion-related acute lung injury.

PMID- 9767753
TI  - [Quality of life of women with stress urinary incontinence with or without
      pollakiuria].
AB  - OBJECTIVES: Assess improvement in quality of life using a validated scale in
      women with urge incontinence or pollakiuria treated with oxybutynine. PATIENTS
      AND METHODS: A prospective open multicentric trial was conducted in 1701 women
      aged 20 to 60 years (mean 47.6) with the last 2 months. Quality of life was
      assessed on the Ditrovie scale before and after a 3-month treatment with
      oxybutynin (7.5 to 15 mg/day). RESULTS: Patient compliance was good (97%) and
      side effects rare (8%) (mainly dry mouth). There was a significant symptom
      improvement (p < or = 0.0001) between day 0 and day 90 after treatment: 48% of
      the women no longer had incontinence with a safety interval of more than 15
      minutes compared with 0.2% prior to treatment; urge incontinence disappeared in
      75% of the 81% affected women; 82% of the women had an intermictional interval
      longer than 2 hours after treatment compared with 33% prior to treatment. There
      was a significant improvement in the quality of life scores after treatment (p <
      0.0001), as assessed by the overall score and subscores (daily life, emotional
      impact, self-image, sleep, well-being). CONCLUSION: These findings demonstrate
      the efficacy of oxybutynine in improving urge incontinence and pollakiuria in
      women, both in terms of symptom relief and quality of life.

PMID- 9767755
TI  - [POEMS syndrome with primary adrenocortical insufficiency].
AB  - BACKGROUND: POEMS syndrome is a multisystem disorder. It usually presents as
      severe polyneuropathy and monoclonal gammapathy associated with endocrinopathies,
      organomegaly, skin hyperpigmentation. CASE REPORT: A patient with POEMS syndrome
      developed primary adrenocortical deficiency revelated by asthenia and
      hyperpigmentation. Hydrocortisone replacement therapy produced a rapidly
      beneficial effect on asthenia and hyperpigmentation. DISCUSSION: Although
      asthenia and skin pigmentation are common in POEMS syndrome, adrenocortical
      deficiency is seldom reported. This endocrinopathy might be underestimated in
      POEMS patients. We suggest systematic screening with a rapid ACTH test in all
      POEMS patients in order to detect underlying adrenal deficiency.

PMID- 9767754
TI  - [Diagnostic criteria for progressive necrotizing external otitis. Are
      scintigraphic findings reliable?].
AB  - OBJECTIVES: Determine the role of 99m technetium scintigraphy for diagnosis in
      progressive necrotizing external otitis and assess the diagnostic criteria of
      this disease. METHOD: A retrospective study was conducted in 16 patients
      hospitalized for suspected progressive necrotizing external otitis. Patient
      characteristics, clinical features, imaging findings and disease course were
      recorded in order to evaluate the classical criteria of diagnosis. RESULTS: The
      clinical course and complementary test results showed that 99m technetium
      scintigraphy lacked specificity for progressive necrotizing external otitis.
      These findings are in disagreement with those reported in the literature.
      CONCLUSION: Patient characteristics and clinical course are key elements for
      early diagnosis of this disease. Scintigraphy findings are contributive only when
      bone lysis (which occurs late) can be evidenced. A prospective study would be
      required to confirm the lack of specificity of scintigraphy in progressive
      necrotizing external otitis.

PMID- 9767756
TI  - [The role of ultrasonography in the detection of neck injuries].

PMID- 9767757
TI  - [Cholecystectomy in respiratory insufficiency: role of laparoscopy with abdominal
      lift].

PMID- 9767758
TI  - [Intestinal lymphangiectasis associated with ileal tuberculosis].

PMID- 9767759
TI  - [Thrombosis, low-molecular-weight heparin-induced thrombocytopenia and labor].

PMID- 9767760
TI  - [Chronic inflammatory bowel disease: new insight from genetics].
AB  - The cause of chronic inflammatory bowel disease remains unknown. A genetic origin
      has been suggested by studies in twins. The gene or genes involved in Crohn's
      disease is probably situated on chromosome 16 and the genes involved in
      ulcerative colitis on chromosomes 2 and 7. It will undoubtedly take some time
      before the exact loci are precisely identified, but current research suggests
      that clinical applications are not far off.

PMID- 9767761
TI  - [Management of sinusitis in adults].

PMID- 9767762
TI  - [NSAID in Alzheimer disease].

PMID- 9767763
TI  - [Epidemiology and genetics of chronic inflammatory bowel disease].

PMID- 9767764
TI  - [Management of multiresistant pulmonary tuberculosis].

PMID- 9767765
TI  - [Prevention of resistance to antibiotics. A complex problem].

PMID- 9767767
TI  - [Prevention of infection at the extreme ages of life].

PMID- 9767766
TI  - [Antibiotic pressure and bacterial resistance in the hospital].

PMID- 9767768
TI  - [Emergence of Gram-positive bacteria in nosocomial transmission].

PMID- 9767769
TI  - [Perspectives in antibiotic prophylaxis].

PMID- 9767770
TI  - [Pneumococcal resistance to beta-lactams: implications for the treatment of acute
      otitis media].

PMID- 9767772
TI  - [Questions on hematology].

PMID- 9767771
TI  - [Prescription of a hematopoietic growth factor, lenograstim, in current practice.
      Results and commentaries of a national survey from April 1995 to March 1996].
AB  - OBJECTIVES: The French drug authorities audited first-time prescription of
      hematopoietic growth factors using a prescription follow-up survey. Data
      collected between April 1995 and March 1996 were analyzed then criticized by
      three clinical experts working in three different areas where lenograstime is
      most widely used. METHODS: First-time prescription data and follow-up information
      were recorded on separate inclusion and follow-up diaries by the prescribing
      physicians. The delivering pharmacies complete the diaries and addressed them to
      the INSERM unit 330 for analysis. RESULTS: There were 7,102 inclusion diaries and
      1376 follow-up diaries from 234 different hospital facilities. Lenograstime was
      most frequently prescribed in patients with lymphoma (19%), breast cancer
      (16.4%), and lung cancer (13.8%). Prescriptions involved 377 different
      chemotherapy protocols, including 196 which concerned a single patient. At the
      first prescription, lenograstime was given as a preventive measure in 61% of the
      cases and for curative therapy in 25.3%. The planned duration of preventive
      treatment was longer than the true period of treatment. DISCUSSION: Pr Rossi,
      hematologist, Pr Misset, cancerologist and Pr Lebeau, pneumologist criticized the
      findings.

PMID- 9767774
TI  - [Questions on pneumology].

PMID- 9767773
TI  - [Questions on oncology].

PMID- 9767775
TI  - [Extensive bone marrow necrosis and thrombotic microangiopathic anemia revealing
      disseminated adenocarcinoma].
AB  - BACKGROUND: Bone marrow necrosis and thrombotic microangiopathy are uncommonly
      associated. We report an observation. CASE REPORT: A 52-year-old man with
      extensive bone marrow necrosis, associated with hemolytic microangiopathic
      anemia, was treated unsuccessfully with corticosteroids and plasmapheresis.
      Outcome was fatal. Autopsy showed disseminated bone marrow necrosis and medullary
      invasion by adenocarcinoma cells in this patient operated 13 years earlier for
      gastric cancer. DISCUSSION: Extensive bone marrow necrosis or thrombotic
      microangiopathy can complicate usually advanced cancer. Prognosis is poor without
      response to chemotherapy. Corticosteroids and plasma exchange are sometimes
      successful. A relative efficacy of treatment with staphylococcal protein A
      immunopheresis is reported by several authors in thrombotic microangiopathy.

PMID- 9767776
TI  - [Hepatic amebiasis: an unusual clinical presentation].
AB  - BACKGROUND: Painful liver enlargement with fever are common signs of hepatic
      ambiasis. Exceptionally, atypical signs may also occur including symptoms
      suggesting renal sepsis. CASE REPORT: An 18-year-old woman from the New Caledonia
      was hospitalized in metropolitan France for suspected right-sided acute
      pyelonephritis. Urinalysis was normal and the kidney ultrasound suggested the
      need for an abdominal CT-scan which evidenced a voluminous 10-cm abscess pus.
      Serology for amebia was positive, confirming the diagnosis of hepatic amebic
      abscess. Outcome was rapidly favorable with intravenous anti-parasite treatment
      amebic abscess. Outcome was rapidly favorable with intravenous anti-parasite
      treatment and percutaneous drainage. DISCUSSION: Atypical signs of hepatic
      ambiasis may mislead diagnosis. The absence of a fetid odor at puncture helps
      guide diagnosis, confirmed by serology. Percutaneous drainage can hbe proposed
      for voluminous abscesses or if the risk of extrahepatic complications is eminent.

PMID- 9767777
TI  - [Major circulatory and medullary eosinophilia revealing renal cell carcinoma].

PMID- 9767778
TI  - [Chylothorax as a complication of Kaposi sarcoma].

PMID- 9767779
TI  - [Borrelia pneumonia: an unusual form of borreliosis].

PMID- 9767780
TI  - [The hematologist, the nutritionist and the plastician: vitamin K deficiency
      during a weight reducing diet].

PMID- 9767781
TI  - [Local corticosteroid therapy in the treatment of lumbar sciatica].

PMID- 9767782
TI  - [Tumor angiogenesis inhibitors: media and scientific aspects].
AB  - Work begun more than 30 years ago at Children's Hospital in Boston led to the
      publication of an article on the antiangiogenic properties of two compounds,
      endostatin and angiostatin (J. Folkman, Nature 1997; 390:404-7). It only took
      weeks for the medias in the US and then in France and the rest of Europe to
      stimulate the fervor of patients for this new 'cure' for cancer. Insight into the
      fundamental role of angiogenesis in locoregional and metastatic development of
      cancer has been accumulated over the last decades. Factors stimulating tumoral
      angiogenesis include aFGF, bFGF, VEGF, angiogenin, and other more recently
      discovered substances. Likewise, factors inhibiting tumoral angiogenesis,
      including angiostatin, have been identified. Angiostatin is a specific inhibitor
      of endothelial cell growth that migh appear rapidly in the serum of patients with
      a primary tumor. Angiostatin could have both local and systemic effects and
      possibly protect against metastatic dissemination in vivo. The importance of
      angiogenesis inhibitors was emphasized at the recent meeting of the American
      Association for Cancer Research (New Orleans March 28-April 1, 1998). To date, at
      least eleven compounds are being tested. Currently, most are in phase 1 or 2; for
      the few in phase 3, marketing approval will undoubtedly require several years. It
      is interesting to note that neither endostatin nor angiostatin are among the list
      of drugs under clinical assessment, first because these small human proteins are
      not available in sufficient quantity for therapeutic trials and secondly, because
      the processes necessary to produce pure and safe compounds remain to be
      developed. Even after these steps have been accomplished, preclinical evaluations
      will have to be performed before the first clinical trials could be envisaged.
      For the time being, antiangiogenesis remains a promising avenue of anti-cancer
      research but neither endostatin nor angiostatin will be available for human
      research for several months at least.

PMID- 9767783
TI  - [Sildenafil: hopeful or unreasonable?].
AB  - Due to its specific action on the intracavernous mechanism of erection,
      sildenafil is the first oral treatment for erectile dysfunction therefore much
      more effective than earlier oral therapies. Patient acceptance is greatly
      improved with the simple oral dose one hour before sexual activity, avoiding
      commonly observed dissatisfaction with intracavernal injections or vacuum
      devices: will its efficiency be the same? Treatment with nitrate derivatives for
      angina pectoris is the major contraindication. Global management, for the patient
      and his partner, remains essential for optimal efficacy of this new compound.
      Considering patient habits and medical prescriptions in France where use of anti
      anxiety and anti-insomnia drugs is relatively high but use of vitamins and
      regenerating drugs relatively low, only the future will tell whether use of
      sildenafil will remain within 'reasonable' limits. No decision concerning
      reimbursement by the French Social Security health care scheme has been made to
      date.

PMID- 9767785
TI  - [Management of VZV infections. Short text of the 11th consensus conference on
      anti-infectious therapies].

PMID- 9767784
TI  - [Cancerology: search for better therapeutic schemes].

PMID- 9767786
TI  - [Management of varicella-zoster virus infections. No systematic vaccination
      against varicella in France].

PMID- 9767787
TI  - [From insulin secretion to insulin therapy].

PMID- 9767788
TI  - [Insulin injections: techniques and plans].

PMID- 9767789
TI  - [Monitoring of the insulin treated diabetic].

PMID- 9767790
TI  - [Radiation-induced rectitis, easy endoscopic diagnosis, an occasionally difficult
      treatment].

PMID- 9767791
TI  - ["Delorme" thickening of the rectal wall, a misleading ultrasound image].

PMID- 9767792
TI  - [Broad-spectrum cephalosporins].

PMID- 9767793
TI  - [Utilization of rapid diagnostic tests for group A streptococcus and and
      bacteriologic and clinical correlations with acute angina in general medicine].
AB  - OBJECTIVES: A prospective study was conducted between November 1995 and May 1996
      by 130 general practitioners in France to assess feasibility of a rapid routine
      diagnostic test for group A streptococcus infection in a general medicine setting
      and to search for bacteriological and clinical correlations. METHODS: A routine
      diagnostic test was performed in all patients presenting acute pharyngitis and
      cultures were ordered in case of positive tests. Among the 2,800 patients
      included, there were 563 children under 14 years and 2,226 adults. The routine
      diagnostic test was positive in 393 cases (14%). A culture was obtained in 375
      case and isolated group A streptococcus in 324 (11.5% of the total population).
      The positive predictive value of the routine diagnostic test was 86.4% in this
      general medicine setting. RESULTS: Comparing clinical signs with the results of
      the routine diagnostic test showed that an erythematous pultaceous aspect of the
      pharynx, severe dysphagia and the presence of enlarged nodes were more frequent
      in patients with streptococcal pharyngitis. The association of these 3 clinical
      signs with fever > 38 degrees C was also more frequent in patients with a
      positive routine diagnostic test (OR = 3.3; 95% CI = 2.5-4.4). The triad
      hoarseness + cough + rhinorrhea was more frequent in subjects with a positive
      routine diagnostic test (22.7% versus 9%; OR = 2.6; 95% CI = 2.1-4.3).
      CONCLUSION: The general practitioners who participated in this study found the
      routine diagnostic test for group A streptococcal pharyngitis was easy to use and
      compatible with everyday practice. This diagnostic tool was seen as a progress in
      the management of acute pharyngitis, but only 53.7% of the practitioners were
      willing to use antibiotics only for cases where a highly specific routine
      diagnostic test performed during the consultation identifies group A
      streptococcus. Lack of reimbursement by the national health assurance however
      makes it impossible to use this test routinely in the general medicine setting.

PMID- 9767794
TI  - [Procalcitonin, C-reactive protein and interleukin 6 in bacterial and viral
      meningitis in children].
AB  - OBJECTIVES: In young children with meningitis, blood or cerebrospinal fluid (CSF)
      analysis cannot differentiate all cases of viral meningitis (VM) from bacterial
      meningitis (BM). Empirical antibiotic therapy is often given. As new markers are
      needed, we compared serum proCalcitonin (PCT) with CSF analysis for C-reactive
      protein (CRP) and interleukin-6 (IL6). PATIENTS AND METHODS: PCT was measured
      with a chemoluminescent assay in the sera of 23 children (aged 3 months to 14
      years) hospitalized for BM and in 51 patients with VM. RESULTS: Initial CRP (mean
      143.3 mg/l, range 28-351 and mean 13.9, range 1-48), CSF proteins (mean 2.2,
      range 0.4-4.74 and mean 0.57, range 0.12-2.72) and white blood cell count in CSF
      (range 240-17500 and 20-3200) in BM and VM respectively, were not sufficiently
      discriminative to distinguish between BM and VM. Twenty-four of the 51 patients
      with VM were given antibiotics. IL6 values at admission showed an overlap zone (>
      100 pg/ml in 7/19 patients with VM and < 100 pg/ml in 1/8 patients with BM. PCT
      was discriminative in all cases: mean PCT in BM was 61 micrograms/l (range 4.8
      335) and 0.33 in VM (range 0-1.7; p < 0.001). No production of PCT was detected
      in CSF. After antibiotic therapy, PCT decreased and reached undetectable levels
      after recovery. CONCLUSION: PCT is a sensitive and specific marker for early
      diagnosis of viral meningitis versus bacterial meningitis in children.

PMID- 9767796
TI  - [Some pediatric associations].

PMID- 9767797
TI  - [Community-acquired purulent meningitis in children].

PMID- 9767800
TI  - [Childhood bacterial meningitis].

PMID- 9767798
TI  - [Treatment with intravenous polyvalent immunoglobulins for autoimmune diseases in
      children].

PMID- 9767795
TI  - [Intracranial hypertension in a newborn treated with quinolone].
AB  - BACKGROUND: Fluoroquinolones have not received administrative authorization for
      use in children, but because of multiresistant pathogens in neonatal intensive
      care, floroquinolones may be the only alternative. CASE REPORT: A premature
      infant exclusively nourished by parenteral nutrition developed enterobacteria
      sepsis. Ceftazidine was given initially but resistance led to the prescription of
      fluoroquinolone. Signs of intracranial hypertension developed 3 days after onset
      of fluoroquinolone treatment and regressed 48 hours after its withdrawal.
      DISCUSSION: The main potential adverse effects with fluoroquinone in the newborn
      are arthropathy, photosensitivity, discoloration of the teeth and neurological
      disorders. Intracranial hypertension is a known complication of nalidixic acid
      both in adults and children, but to our knowledge has not been previously with
      floroquinolone in the newborn.

PMID- 9767799
TI  - [Acute rheumatic fever in today's children].

PMID- 9767801
TI  - [Childhood meningitis. Current data on physiopathology].

PMID- 9767802
TI  - [Childhood bacterial meningitis. Bacterial epidemiology and antibiotic
      resistance].

PMID- 9767803
TI  - [Childhood bacterial meningitis. Antibiotic strategies].

PMID- 9767804
TI  - [Childhood bacterial meningitis. Role of corticosteroids].

PMID- 9767805
TI  - [Lytic epiphyseal-metaphyseal lesion].

PMID- 9767806
TI  - [Severe pneumonia with a pneumococcal aspect during an ornithosis outbreak].
AB  - OBJECTIVES: To describe the clinical, radiological and biological features of
      Chlamydia psittaci pneumonia. METHODS: A pneumonia outbreak occurred in a healthy
      middle-aged population working in a poultry slaughterhouse. Systematic serology
      (2 samples at 5 weeks intervals) provided the diagnosis of Chlamydia psittaci
      pneumonia in 6 patients. Patient files were analyzed retrospectively. RESULTS:
      The clinical presentations in this series of pneumonia were particularly
      homogeneous with a pneumococcal profile in all 6 cases: sudden onset, temperature
      above 39 degrees C, lobar alveolar involvement, hypoxemia, hyperleukocytosis and
      liver dysfunction. One case of hallucinatory delirium was observed. The patients
      were given spiramycin (9 million units per day for 3 weeks) and all recovered
      rapidly with no complications. CONCLUSION: The unusual virulence of the Chlamydia
      psittaci and very important inoculum were probably involved in this outbreak
      because of the severity of the pulmonary features and the short exposure of some
      patients to the bacteria. These cases suggest that the prevention of ornithosis
      in poultry slaughterhouses should be reinforced.

PMID- 9767807
TI  - [Spontaneous positive end-expiratory pressure ventilation in elderly patients
      with cardiogenic pulmonary edema. Assessment in an emergency admissions unit].
AB  - OBJECTIVES: Intubation and ventilatory assistance are often required in patients
      presenting severe hypoxemic respiratory distress, but may be contraindicated in
      elderly subjects due to an underlying condition. The aim of this study was to
      assess the feasibility, acceptability and contribution of early assistance with
      spontaneous positive end-expiratory pressure ventilation for elderly subjects
      admitted to an emergency unit for acute respiratory distress due to cardiogenic
      pulmonary edema. PATIENTS AND METHODS: In our emergency admission unit, all
      patients with life-threatening hypoxemic respiratory distress are initially
      assisted with noninvasive spontaneous positive end-expiratory pressure
      ventilation using a standardized commercial device. We retrospectively analyzed
      the the files of all patients aged over 70 years who were treated with this
      standard protocol for cardiogenic pulmonary edema from April 1996 through
      September 1997. RESULTS: During the study period, 36 patients aged over 70 years
      required ventilatory assistance according to the standard protocol. Intubation
      was not reasonable in most of the patients (n = 30). After 1 hour of ventilation,
      none of the patients developed clinical signs of life-threatening distress. Blood
      gases demonstrated improved oxygenation (AEPO2 = +184.9 +/- 105.4 mmHg; p <
      0.000001). Thirty-two patients were considered to be cured (88.9%) and were
      discharged; the cardiovascular condition was fatal in 4 patients (11.1%).
      CONCLUSION: The rapid improvement in clinical signs and blood gases as well as
      the final outcome suggests that early assistance with spontaneous positive end
      expiratory pressure ventilation is warranted at admission for elderly patients
      with respiratory distress due to cardiogenic pulmonary edema. Compared with a
      control group of hospitalized patients cared for during the preceding year and
      who were not treated with the standard protocol, we also demonstrated a clear
      improvement in mortality (11% versus 20%).

PMID- 9767808
TI  - [Diabetes insipidus with a hypothalamo-hypophyseal morphologic anomaly during a
      pregnancy].
AB  - BACKGROUND: Diabetes insipidus is uncommon in pregnancy. Despite physiological
      modifications in hydroelectrolytic balance during normal pregnancy, the capacity
      of the kidney to concentrate urine is preserved, partially due to lower
      vasopressin secretion. CASE REPORT: A young woman developed diabetes insipidus
      during the third trimester of normal pregnancy. The disease regressed totally
      after delivery. However, magnetic resonance imaging revealed a persistent
      expansive intrasellar image with a high-intensity signal. DISCUSSION: Onset of
      diabetes insipidus is usually rapidly progressive in pregnancy. Occurring
      generally during the third trimester in normal pregnancies, diabetes insipidus is
      generally well tolerated and responds to dDAVP, usually without pituitary
      abnormally, and regresses after delivery. Two types are distinguished: partially
      latent diabetes insipidus occurring during pregnancy and due to a central rather
      than nephrogenic origin; and excessive vasopressinase activity leading to
      diabetes insipidus usually associated with liver anomalies and high frequency of
      pre-eclampsia. During normal pregnancy, the size of the anterior pituitary
      increases and the normal high-intensity signal in the posterior pituitary seen on
      MRI usually regresses or disappears. In diabetes insipidus, the posterior
      pituitary hypersignal image generally disappears, reflecting reduced vasopressin
      storage. Few observations of diabetes insipidus occurring during pregnancy have
      been reported with morphological explorations. Most have described a "normal"
      aspect of the pituitary, specifically in the post partum period. In our patient,
      the weak vasopressin response to the end of water restriction at post partum when
      the diabetes insipidus symptoms had disappeared would suggest partial central
      diabetes insipidus revealed by pregnancy. Other pathologies involving this region
      could also be involved due to the unusual and persistent sellar image, with an
      expansive process showing a high intensity signal on MRI. An asymptomatic
      craniopharyngioma cyst was hypothesized and would be more compatible with the
      observed symptoms.

PMID- 9767809
TI  - [Massive poisoning by African bee stings].
AB  - BACKGROUND: Bee stings can cause severe toxic effects when envenomation is
      massive. CASE REPORT: While touring in Casamance (Southern Senegal) a white male
      was severely stung by a swarm of African bees. The massive envenomation caused
      rhabdomyolysis, hemolysis and acute renal failure. Pathology examination of
      kidney and bladder specimens showed vasculitis affecting both arteries and veins.
      The patient was treated with several hemodialysis sessions and renal function
      returned to normal three months after the incident. DISCUSSION: Bees in Africa,
      known as "killer bees", are particularly aggressive. They have recently been
      imported from tropical zones in America where a large number of deaths have been
      reported. Most cases of massive envenomation have shown acute tubular necrosis or
      renal involvement with myoglobinuria or hemoglobinuria. The renal pathology
      observed in our case is not usually described.

PMID- 9767810
TI  - [Sign of Lazarus after brain death].

PMID- 9767811
TI  - [Iatrogenic aseptic meningitis].

PMID- 9767812
TI  - [Parietal abdominal hematoma after combined acenocoumarol and roxithromycin
      treatment].

PMID- 9767813
TI  - [Relapsing Campylobacter coli bacteremia in a hypogammaglobulinemic patient].

PMID- 9767817
TI  - [Endobronchial photodynamic therapy in France].

PMID- 9767814
TI  - [Candida parapsilosis: an increasingly frequent cause of nosocomial fungemia].

PMID- 9767815
TI  - [Use of non-invasive positive pressure ventilation for cardiogenic pulmonary
      edema in emergency care units].
AB  - The work reported by L'Her et al. in this issue of La Presse Medicale
      demonstrates the feasibility of applying simple intensive care techniques in
      situations frequently encountered in emergency care units. These authors used a
      face mask for continuous positive pressure ventilation in patients over 70 years
      of age admitted for respiratory distress related to cardiogenic pulmonary edema.
      In these elderly patients, the authors noted an improvement in blood gases,
      respiratory rate and heart rate and did not observe any secondary effect. Acute
      respiratory failure was cured in 90% of the cases without referral to the
      intensive care unit. The mechanism of action of continuous positive airway
      pressure, or spontaneous ventilation with positive expiratory pressure, is
      different from simple oxygen therapy. Two mechanisms are intimately related. The
      main effect is ventilatory assistance resulting from a "re-aeration" of the
      pulmonary parenchyma which increases compliance and reduces work required to
      overcome elastic retraction forces. Likewise the increased pulmonary volume
      reduces pulmonary resistance. Positive airway pressure also has an effect on left
      ventricular function. Indeed, after-load is reduced by the reduction in the large
      negative intrathoracic pressure swing. Lower energy expenditure required for
      respiration also greatly reduces total oxygen consumption and improved blood
      gases favor oxygen supply to the myocardium. The contraindications of continuous
      positive airway pressure are related to abnormal control of the upper airways and
      major hemodynamic disorders. Prudence is also required in case of shock due to
      the risk of major respiratory muscle fatigue. The question could also be raised
      as to the risk in elderly patients where cardiogenic pulmonary edema is often
      associated with a certain degree of chronic bronchitis. It is now known that
      these patients have an intrinsic positive expiratory pressure which considerably
      increases respiratory work. Symptomatic treatment in this type of disorder is
      mechanical and continuous positive airway pressure diminishes this work.
      Cardiogenic pulmonary edema in the elderly is thus an excellent indication for
      spontaneous ventilation with positive expiratory pressure. Improvement in these
      simple techniques, their widespread use and a better understanding of their
      limitations remain important challenges for the future.

PMID- 9767816
TI  - [Von Hippel-Lindau disease: a hereditary disease that impacts multiple tissues].

PMID- 9767818
TI  - [Late potentials in chronic alcoholics].
AB  - OBJECTIVE: Cardiac arrest is the most frequent cause of death in chronic
      alcoholics. Detection of late potentials in this population could be helpful in
      screening from early signs of myocardial disorders and identifying patients at
      risk of severe ventricular dysrythmia. PATIENTS AND METHODS: A prospective study
      of late potentials was conducted in 53 subjects (mean age 49 +/- 10 years) with a
      history of long-standing alcohol abuse (mean 13.6 +/- 8.5 years, mean daily
      alcohol intake 86 +/- 30 g). After a period of abstinence, the following
      explorations were performed: liver tests, liver biopsy, electrocardiogram,
      echocardiography, Holter recording. RESULTS: Among the 53 patients, 37% were
      positive for 2 of the 3 criteria for late potentials. There was a strong
      correlation between the duration of alcohol abuse and presence of late potentials
      (p = 0.006, r = 0.37). The percentage of hepatic steatosis was higher in
      alcoholic subjects with late potentials (34% versus 23%; p = 0.05) and was
      correlated with the number of positive criteria for late potentials (p = 0.05, r
      = 0.328). Finally, the presence of late potentials was also correlated with the
      following laboratory results: serum gamma glutamyltranspeptidase (p = 0.031),
      serum aspartate amino transferase (p = 0.033), serum alkaline phosphatases (p =
      0.0025). CONCLUSION: Late potentials can be detected easily although their
      prognostic value remains to be determined. They could be an early marker of
      infraclinical myocardial lesions.

PMID- 9767819
TI  - [Prognosis after myocardial infarct in a diabetic patient: results of coronary
      intensive care unit epidemiological study].
AB  - OBJECTIVE: Determine early and mid-term mortality in diabetic patients with
      myocardial infarction and ascertain whether diabetes is an independent prognosis
      factor. PATIENTS AND METHODS: All patients admitted to an intensive care unit
      within 48 hours of the first signs of myocardial infarction were included in the
      study. Diabetic status was recorded at admission. Early mortality (5 day) and 1
      year mortality was compared between diabetic and non-diabetic patients.
      Multivariate analysis was used to determine the predictive value of diabetic
      status as an independent factor. RESULTS: 2527 patients, including 440 diabetics
      (17%) and 2087 non-diabetics (83%) were followed at 5 days; 2125 patients,
      including 364 diabetics (17%) and 1761 non-diabetics (83%) were followed to 1
      year. Diabetes was more frequent in older patients and in women. Mortality in
      diabetic patients was higher than in non-diabetics. At 5 days, mortality was
      10.4% versus 17.6% (p < 0.001). Multivariate analysis did not confirm diabetic
      status as an independent risk factor for death at 5 days. Inversely, at 1 year,
      diabetic status was an independent risk factor (RR = 1.4; 95% CI = 1.1 -1.8; p =
      0.004). CONCLUSION: Diabetes is associated with poor prognosis after myocardial
      infarction. After correction for other risk factors, diabetes is an independent
      risk factor which must be taken into account when managien after myocardial
      infarction.

PMID- 9767820
TI  - [Lactobacillus acidophilus endocarditis].
AB  - BACKGROUND: Lactobacillus is a commensal germ found in the buccal cavity, the
      digestive tract and the vagina. Usually non-pathogenic except in case of dental
      caries, it can occasionally be the causal agent in severe endocarditis. CASE
      REPORT: A 70-year-old woman developed endocarditis on an aortic valve
      bioprosthesis. Lactobacillus acidophilus was isolated from blood cultures of the
      valve after surgery. COMMENTS: Forty-four cases of Lactobacillus endocarditis
      have been reported in the literature to date. Mortality is high (26%). The main
      difficulty in treatment is germ tolerance to penicillin and aminosides found in
      all cases. Cure requires high dose parenteral antibiotics and surgery in many
      cases (26%).

PMID- 9767821
TI  - [Migration of a clavicular bone wire acutely perforating the ascending aorta].

PMID- 9767823
TI  - [Hemodialysis of the elderly patient: consider the coronary arteries].

PMID- 9767822
TI  - [Quality and accreditation in health facilities].

PMID- 9767824
TI  - [Specifically adapted management of diabetics after myocardial infarct].
AB  - Approximately 20% of all patients hospitalized for myocardial infarction have
      diabetes. The percentage has been increasing constantly and mortality is
      significantly higher in these patients. The highest rate is observed in women.
      Despite continuing progress in patient management there has been no reduction in
      the overmortality after myocardial infarction in diabetic patients. The majority
      of these deaths are unwarranted and could be avoided if diabetic patients were
      given specifically adapted treatment after myocardial infarction. Unfortunately,
      as shown by the EURASPIRE study, there is a gap between intensive care unit
      discharge prescriptions and follow-up care. With the explosive "epidemic" of
      noninsulin-diabetes and population aging the number of patients with coronary
      artery disease and diabetes will rise in the future. Wouldn't it be reasonable to
      establish special cardiodiabetic units where such patients could benefit from
      close, and daily, cooperation between diabetologists and cardiologists? Such
      facilities could be expected to significantly reduce the overmortality in
      diabetic patients after myocardial infarction.

PMID- 9767825
TI  - [Prevention of bacterial endocarditis. New recommendations from the American
      Heart Association].

PMID- 9767826
TI  - [Congenital long QT syndrome].
AB  - SEVERAL FORMS: Congenital long QT syndrome is a clinically (with and without
      deafness) and genetically (recessive or dominant autosomal inheritance)
      heterogeneous entity characterized by a long QT interval on the ECG associated
      with the risk of severe ventricular arrhythmia (torsade de pointes, ventricular
      fibrillation) and subsequent syncope or sudden death. GENETIC DATA: This rare
      familial syndrome is transmitted by different modes of inheritance and occurs in
      subjects with a morphologically normal heart. The severity of the prognosis
      justifies screening tests. The genetic origin of the disease has been confirmed
      and at least 5 loci and 4 genes have been identified, giving a perfect
      illustration of adrenergic ventricular rhythm disorders. Beta-blockers are used
      as first line treatment in symptomatic patients. PREVENTION: All drugs favoring
      QT interval lengthening are contraindicated in all subjects with a genetic
      anomaly. All members of the direct family must have a Holter recording and
      genotype in order to identify mutation carriers or asymptomatic patients.

PMID- 9767827
TI  - [Myocardial viability. The concept of myocardial viability].
AB  - MYOCARDIAL VIABILITY: Certain zones of ischemic, akinetic or severely hypokinetic
      myocardium are capable of recovering normal contractile function. This is termed
      myocardial viability and occurs in two different situations: myocardial stunning
      and myocardial hibernation. MYOCARDIAL STUNNING: This term designates temporary
      but prolonged impairment of myocardial function resulting from a brief episode of
      ischemia before reperfusion. MYOCARDIAL HIBERNATION: Hibernation designates
      prolonged but potentially reversible myocardial contractile dysfunction caused by
      chronic myocardial ischemia and persisting at least until blood flow is restored.
      CLINICAL CONSEQUENCES: Theoretically reversible, myocardial stunning or
      hibernation can have devastating effects if they persist too long.
      Revascularization with angioplasty or bypass surgery is indicated. DIAGNOSIS: The
      degree of myocardial viability in akinetic zones can be determined by assessing
      preserved inotropic capacity with stress echocardiography and/or evidencing
      metabolic activity with isotopic techniques (myocardial scintigraphy, positron
      emission tomography).

PMID- 9767828
TI  - [Myocardial viability. Study of viability by myocardial scintigraphy].
AB  - FUNDAMENTAL PRINCIPLES: Myocardial scintigraphy is a metabolic approach to
      myocardial viability visualizing the localization, the extent and to some degree
      the quantity of non-functional yet viable myocardial tissue. Potential for
      functional recovery cannot be ascertained directly from the scintigram but can be
      inferred from commonly observed behavior after blood flow has been restored.
      Myocardial scintigraphy is thus fundamentally different from other functional
      exploration methods such as echocardiography or nuclear magnetic resonance
      imaging which can detect residual contractile capacity unmasked by inotropic
      stimulation. It must be remembered however that such 'forced' contractility may
      not necessarily be expresses spontaneously after revascularization and that,
      however detected, truly viable myocardium may not recover normal contractility
      after reperfusion when associated with non-transmural infarction or diffuse
      fibrosis. PET AND THALLIUM 201 SCANS: Positron emission tomography (PET) is the
      gold standard. Accomplished after administration of an isotope labeled substance
      (18-fluoro-deoxyglucose, FDG), the PET scan visualizes metabolic activity in
      viable myocardium. Special equipment is however required and facilities are
      limited, particularly in France. Thallium 201 scans can be acquired with
      conventional gamma cameras and protocols have been widely developed with nearly
      equivalent performance in certain situations of doubtful residual viability after
      post-infarction thrombolysis or angioplasty. It must be noted however that in
      such cases, search for homolateral or contralateral ischemia may be the main
      objective rather than the detection of residual viability. A 3-step thallium 201
      scintigraphy protocol with stress, 4-hr redistribution then imaging after
      reinjection is usually sufficient to document ischemia or viability warranting
      revascularization. The problem is quite different for patients with major
      myocardial dysfunction and histological remodeling due to hypokinetic dilated
      cardiomyopathy. In such types of myocardium, chances of recovering inotropic
      capacity are quite limited and detecting viable tissue would be technically
      difficult; however with a proper protocol (without stress, resting images late
      after injection), thallium 201 scintigraphy can be helpful. PERFORMANCE: Data in
      the literature shows that isotopic techniques lack specificity by overestimating
      the extent of viable tissue capable of recovering contractility. Actually this
      could be seen as an advantage since the consequences of missing even a small
      chance for revascularization warrant risking an ineffective procedure for a
      patient whose only alternative is heart transplantation. This situation explains
      why 18-FDG PET exploration should be performed even if the thallium scintigram
      leaves very little room for hope of recovering viable myocardium in patients with
      terminal disease. PERSPECTIVES: Isotopic exploration of the myocardium is a
      moving field and routine practice can expect to benefit from research conducted
      in pioneer centers. The future offers two main perspectives: the development of
      metabolic tracers giving more precision than thallium 201 (for example isotope
      labeled fatty acids); and technical advances in conventional gamma cameras more
      adapted to the physical characteristics of 18 FDG used for PET scans.
      Scintigraphy is an indispensible tool for metabolic exploration of the
      myocardium. Only nuclear magnetic resonance spectroscopy may provide comparable
      results.

PMID- 9767830
TI  - [Nitric oxide (NO), vascular protection factor. Biology, physiological role and
      biochemistry of NO].
AB  - VASOMOTRICITY: The vascular endothelium plays a key role in vasomotricity by
      producing a number of factors which modulate smooth muscle relaxation and
      contraction. Nitric oxide (NO) has been found to be one of the most important
      relaxation factors. NO SYNTHESIS: Nitric oxide is synthesized from L-arginine by
      NO-synthetase whose activity is regulated by intracellular calcium concentration
      and modulated by pharmacological compounds such as acetylcholine, 5
      hydroxytryptamine, bradykinin and ADP as well as the sheer forces produced by
      blood flow. MODE OF ACTION: NO stimulates soluble guanylate cyclase in smooth
      muscles. Its action is mediated by increased intracellular cGMP which provokes
      smooth muscle relaxation. ACTIONS OF NO: The physiological role of NO produced by
      the vascular endothelium is quite complex and incompletely elucidated. NO helps
      maintain adequate blood supply to tissues by reacting rapidly to changes in
      pharmacological and mechanical stimuli. It opposes the direct vasoconstrictor
      effect of certain factors in the blood stream and its action on platelets and
      endogenous fibrinolysis helps prevent thrombus formation.

PMID- 9767829
TI  - [Myocardial viability. Myocardial viability post-infarct: contribution of
      dobutamine-echography].
AB  - ROUTINE EXPLORATION: Echocardiography during dopamine perfusion has been widely
      proven as an effective tool for determining myocardial viability. Dobutamine has
      marketing authorization in France for stress-echocardiography and is widely used
      in clinical practice outside research protocols. The exploration must however be
      conducted within an appropriately equipped cardiac intensive care unit. Stress
      echocardiography has certain advantages over isotropic techniques, in terms of
      equipment costs, examination time and exposure to isotopes. POST-INFARCTION:
      Dobutamine-echocardiography enables detection of viable myocardium within the
      infarct zone, evaluates the degree of residual ischemia in the infarct zone and
      provides information on prognosis. It would not however be reasonable to perform
      stress-echocardiography as a first line exploration after infarction.
      International guidelines recommend a sub-maximal ECG exercise test prior to
      coronarography. The contribution of stress-echocardiography after infarction is
      its ability to give precise information on myocardial viability and residual
      ischemia in one or more territories to compare with coronary lesions, thus
      allowing indication for revascularization. CHRONIC ISCHEMIC CARDIOPATHY:
      Dobutamine-echocardiography can be used to detect hibernating myocardium in
      patients with chronic ischemic cardiopathy. In this indication, the sensitivity
      of stress-echocardiography is slightly lower than thallium scintigraphy, but its
      specificity and positive predictive values are higher. The best predictive value
      is obtained with bimodal dobutamine-echocardiography: improve-med thickening at
      low doses and a degradation at high dose is predictive of functional improvement
      after revascularization in 72% of the cases. In more severe cases with ejection
      fraction < 35%, improvement in hibernating myocardium after revascularization
      leads to a significant improvement in left ventricular ejection fraction.

PMID- 9767831
TI  - [Nitric oxide (NO), vascular protection factor. NO related cardiovascular
      diseases].
AB  - ALTERATIONS OF THE ENDOTHELIUM: Because of its anatomic position between
      circulating blood and smooth muscle cells, the vascular endothelium is a prime
      target for cardiovascular diseases such as hypertension, hypercholesterolemia,
      diabetes or ischemia. The morphological changes occurring in the endothelium have
      been known for many years, but it was only recently that the functional
      alterations have been described. IMPACT OF NO: Under physiological conditions,
      the vascular endothelium plays a protective role by secreting relaxation factors.
      In the disease state, the synthesis and release of NO may be reduced or even
      abolished. The exact significance of endothelium-dependent vasodilatation
      disorders remains a topic of research, but the properties of NO strongly suggest
      it is involved in several diseases. For some diseases it is still a question as
      to whether the observed anomalies are the cause or the consequence of the
      underlying disease. DISEASE-SPECIFIC CHANGES: NO is known to be reduced in
      atherosclerosis, either because of less synthesis or accelerated degradation. In
      different experimental modules of hypertension, the baseline level of NO release
      appears to be decreased. Conversely, NO release can be normal, reduced or
      increased in diabetes. In heart failure, there appears to be not only a permanent
      alteration in NO secretion, but also an increase in factors stimulating vascular
      contraction, contributing to an altered capacity for vascular adaptation in these
      patients.

PMID- 9767833
TI  - [Ascending aorta dissection. Transesophageal color doppler ultrasonography].

PMID- 9767834
TI  - [Prevalence and incidence of cytomegalovirus infection in patients infected with
      HIV-1. SEROCO group].
AB  - OBJECTIVES: To study prevalence of the cytomegalovirus (CMV) infection as well as
      incidence of the CMV seroconversions in HIV-infected subjects enrolled in the
      French multicentric cohort SEROCO. METHOD: Prevalence of CMV infection at
      inclusion in the cohort was estimated from 1504 HIV-infected subjects. Incidence
      of the CMV seroconversion was estimated from 184 subjects CMV seronegative at
      inclusion. Cox model was used to identify independent factors related to CMV
      seroconversion. RESULTS: CMV prevalence was high (87.2%) mainly in homosexual
      men. The incidence of the CMV seroconversions was also high (9, 18/100 person
      years), particularly in homosexual men, in subjects declaring sexual intercourse
      with occasional partner, and in those declaring a sexually transmitted disease
      during the follow-up. CONCLUSION: The risk to develop serious disease related to
      CMV in subjects with AIDS being particularly high when the CMV primary infection
      occurs during the course of the HIV infection, the prevention of CMV primary
      infections is thus a major element in the counselling of HIV-infected subjects.

PMID- 9767835
TI  - [Aorto-coronary bypass].
AB  - OBJECTIVES: Saphenous grafts used for coronary artery bypass are classically
      dissected via a continuous incision of the leg, the thigh or both. Recently, a
      new video-surgery technique has been introduced in an attempt to reduce the
      trauma of saphenous vein dissection. The aim of this work was to evaluate the
      possible benefits of this new technique compared with classical dissection.
      PATIENTS AND METHODS: Sixty patients requiring coronary artery bypass grafts were
      included in this study and randomly divided into two groups. In group I (30
      patients) the saphenous vein was dissected according to the classical technique.
      The video-surgery technique was used for the other 30 patients in group II. The
      two groups were not significantly different for mean age, sex ratio, or history
      of diabetes or lower limb arteriopathy. The same number of bypasses was performed
      in both groups (2.6 +/- 0.7). Outcome was compared for: dissection related
      complications (hematomas, infections), length of the skin incision over the
      length of the dissected vein, duration of the dissection procedure, and post
      operative pain. RESULTS: A leg incision was used in 28 cases out of 30 cases in
      both groups. The length of the saphenous vein dissected was 27.6 cm in group I
      and 21.8 cm in group II. The length of the skin incision was 27 cm in group I and
      only 4.7 cm in the video-surgery group II, giving an incision/vein ratio of 97%
      and 21% respectively. Operative time was however 37.9 min for group I and 48.5
      min for group II. There was no significant difference between the groups for
      hematoma formation or infection but the patients in the video-surgery group
      experienced less post-operative pain. CONCLUSION: Besides an improvement in the
      esthetic result, video-surgery dissection of the saphenous vein reduces post
      operative pain at the cost of a slightly longer operative procedure.

PMID- 9767832
TI  - [Nitric oxide (NO), vascular protection factor. NO: role in aging].
AB  - AGING PROCESS: There is a large body of experimental and clinical data
      demonstrating that endothelial dysfunction is encountered not only in disease
      states such as atherosclerosis, hypertension, heart failure or diabetes, but also
      in the normal physiological process of aging. Currently available data show that
      endothelium-dependent function declines with age. The fact that this same decline
      is observed in patients with hypertension suggests that age is an independent
      factor capable of provoking changes in the vascular endothelium. CAUSAL
      MECHANISMS: It is often suggested that altered NO synthesis from L-arginine
      and/or increased production of contraction factors play a role in the aggravation
      of endothelial and parietal lesions and would thus affect the natural history of
      the disease process. HUMAN STUDIES: Ongoing studies in man tend to confirm
      experimental data obtained in animal models; treatment protocols could be adapted
      using compounds aimed at restoring normal endothelial function.

PMID- 9767836
TI  - [Cerebral and pulmonary miliary tuberculosis in an immunocompetent patient:
      aggravation in an adequately treated patient].
AB  - BACKGROUND: Extrapulmonary localizations are observed in 20% of tuberculosis
      cases, mainly in immunosuppressed patients. Prognosis is poor in case of
      relatively uncommon cerebral localizations and miliary dissemination, especially
      if treatment is initiated in late stages. We report a case of disseminated
      tuberculosis associated with cerebral and pulmonary localizations in an
      immunocompetent patient. THe disease progressed despite adapted treatment. CASE
      REPORT: A young immunocompetent man with an uneventful history developed miliary
      tuberculosis with pulmonary localizations visualized on the computed tomography
      (CT) of the thorax. Brain CT was normal, but magnetic resonance imaging revealed
      several intracranial lesions. The disease course was marked by development of
      neurological symptoms and progression of the cerebral lesions after one month of
      treatment. No evidence of therapeutic failure (insufficient dosing, non
      compliance, primary resistance) could be identified. DISCUSSION: Magnetic
      resonance imaging provides a more precise evaluation of tuberculosis lesions in
      the brain. Early antituberculosis therapy associated with corticosteroids can
      improve prognosis. Clinicians should be aware that cerebral lesions may continue
      to progress despite appropriate treatment, a course which is not satisfactorily
      explained by any current pathogenic hypothesis.

PMID- 9767839
TI  - [Hypersensitivity vasculitis after hepatitis B vaccination].

PMID- 9767838
TI  - [Portal thrombosis and anticardiolipin antibodies association in an HIV-2
      infected patient].

PMID- 9767837
TI  - [Diffuse digestive tract B-cell lymphoma manifesting as exudative enteropathy].
AB  - BACKGROUND: Early manifestations of primary lymphomas of the digestive tract
      generally include general signs and abdominal pain. Diarrhea is uncommon and may
      result from several mechanisms. We report a case of primary lymphoma of the
      digestive tract in a patient presenting exsudative enteropathy. CASE REPORT: A 68
      year-old woman was hospitalized for profuse diarrhea of 15 days duration.
      Laboratory tests showed major hypoalbuminemia. Malabsorption could not be
      evidenced and no infectious foyer was found. Biopsies at different levels of the
      digestive tract showed mucosal invasion by MALT type B-cell lymphoma. The
      clinical course was initially favorable after chemotherapy. DISCUSSION:
      Classification of digestive tract lymphomas differentiates MALT type B-cell
      lymphoma (the most frequently encountered type in western countries),
      Mediterranean lymphomas, and T-cell lymphomas generally complicating coeliac
      disease. MALT type lymphomas may occur in association with Helicobacter pylori
      infection, usually in a gastric localization. Multiple localizations are uncommon
      and diffuse involvement of the digestive tract as in our observation appears
      exceptional. This extension would explain the exsudative enteropathy which
      regressed with chemotherapy.

PMID- 9767841
TI  - [Unique cerebral metastasis of ovarian origin].

PMID- 9767842
TI  - [Cystic form of bronchopulmonary cancer associated by a malignant non-Hodgkin
      lymphoma].

PMID- 9767840
TI  - [Lupus erythematosus probably induced by carbamazepine, associated with
      complement fraction deficiency].

PMID- 9767844
TI  - [Cervical-vaginal smears: an unpopular test!].
AB  - No screening test for cancer in asymptomatic patients can match the performance
      level of the Pap smear, yet no other screening test has been so strongly
      criticized in the popular press. For a large part, this paradoxical situation,
      greatly influenced by public opinion in the United States, has arisen from a
      utopic desire for a "perfect" screening system. Actually, though the Pap smear
      will never be 100% effective, it has made it possible to greatly reduce the
      prevalence of invasive cervical cancer. The fact that total eradication has not
      been achieved is not a sign of poor performance, but rather a signal for further
      improvement. Public education should be reinforced so the entire population,
      especially high risk groups of older women and those living in socially
      underprivileged conditions, can benefit from Pap smear screening programs.
      Clinicians and cytologists must also continue their efforts to assure quality
      smears and cytopathological examinations. In France, the Association for quality
      assurance in anatomy and pathological cytology, the Centers for collecting
      information on anatomy and pathological cytology, and the High Counsel for Public
      Health have taken innovative steps in this direction. The cytology report must
      also be written in a clear language, including a statement regarding the adequacy
      of the specimen, the description of the cells observed, a diagnosis and the use
      of an internationally accepted classification. Finally, patient follow-up is
      mandatory since the Pap smear technique is a screening method and cannot provide
      a definitive diagnosis. All positive smears must be confirmed by colposcopy and
      histologic assessment. Correctly used, the Pap smear remains the method of choice
      for the eradication of cervical cancer.

PMID- 9767843
TI  - [Teaching ethics in French medical schools: evolution or revolution ?].
AB  - Ethics was introduced as subject matter in French medical schools only recently
      despite a rich historical context where scientific legitimacy, humanistic
      exigencies and anglo-saxon influence have all played a role. Ten years after the
      thesis presented by Bastian in 1986, a survey of French medical schools shows
      that ethics has become an integral part of the curriculum. Ethics has tended to
      become a discipline on its own, separate from law and deontology. However, the
      lack of specific courses on concentration in the first years of the curriculum
      show that there is much room for growth in the discipline of medical ethics.

PMID- 9767846
TI  - [Intensive therapy in non-Hodgkins lymphoma. Indications and modalities].

PMID- 9767845
TI  - [Diagnosis of pulmonary embolism: value of imaging].

PMID- 9767847
TI  - [Peptic esophagitis and Barrett's esophagus: two often associated complication of
      hiatal hernia].

PMID- 9767848
TI  - [Nosocomial infections in intensive care].

PMID- 9767851
TI  - [Cerebral abscess during a severe form of Salmonella typhimurium bacteremia in an
      immunocompetent patient].
AB  - BACKGROUND: Bacteremia rarely occurs in non-typhoid salmonella infections and the
      development of a brain abscess is exceptional. CASE REPORT: An immunocompetent
      patient developed severe Salmonella typhimurium bacteremia leading to septic
      shock and acute respiratory distress and acute renal failure. A brain abscess,
      which was not present on the initial brain tomodensitometry, developed and
      totally regressed after antibiotic therapy. DISCUSSION: We were unable to
      identify and factor favoring the development of salmonella bacteremia in this
      patient. There were no cerebral lesions on the initial brain tomodensitometry
      considered to be normal. To our knowledge, this is the first report of Salmonella
      typhimurium brain abscess in an immunocompetent subject.

PMID- 9767849
TI  - [Vitamin D status in aged subjects. Study of a Lebanese population].
AB  - OBJECTIVES: To evaluate vitamin D status in two subgroups of the Lebanese aged
      population. To compare results with reference values observed in healthy young
      volunteers. METHODS: Fifty aged institutionalized patients (25 men and 25 women)
      and 51 aged ambulatory subjects (25 men and 26 women) underwent the following
      explorations during winter: serum 25-OH vitamin D, parathyroid hormone, corrected
      serum calcium, phosphorus, creatinine, and alkaline phosphatases and urinary
      calcium/creatinine. Serum 25-OH vitamin D and urinary calcium/creatinine were
      also measured in 34 healthy young volunteers. RESULTS: Serum 25-OH vitamin D
      levels in 25 ambulatory subjects (49%) and 30 institutionalized patients (60%)
      were below 10 ng/ml. There was non significant difference in 25-OH vitamin D
      levels between the ambulatory and institutionalized aged populations, nor between
      aged women and aged men. Parathyroid hormone, alkaline phosphatases and urinary
      calcium/creatinine levels were higher in the institutionalized population than in
      the ambulatory population (p = 0.07; p = 0.0001; p = 0.0001 respectively). Aged
      women had higher parathyroid hormone and calcium/creatine levels than aged men (p
      = 0.005; p = 0.005 respectively). Finally, in the young population, 25-OH vitamin
      D was higher than in the aged institutionalized and ambulatory populations (p =
      0.0001 and p = 0.0009 respectively). An inverse non-significant correlation (r = 
      0.16) was found between parathyroid hormone and 25-OH vitamin D. CONCLUSION: Our
      results show that even in a sunny country like Lebanon, vitamin D deficiency is
      often observed. The degree of deficiency probably lies between that observed in
      Europe and the United States. It could be related to low vitamin D diet.

PMID- 9767850
TI  - [Initial antiretroviral prescriptions in patients with HIV. Second semester 1994
      second semester 1996].
AB  - OBJECTIVES: The nature of antiretroviral therapy has radically changed these last
      years. A study has been conducted on data obtained from the DMI2 information
      system to evaluate changes on treatments, immunity and transmission profile of
      the patient naive to antiretroviral therapy when initiating a therapy. METHODS:
      DMI2 is a national, multicentered database which contains medical,
      epidemiological and economic information on hospital care for HIV patients. This
      study, on 18,510 patients followed up in one of the fifty hospitals belonging to
      the Centers for Information and Care of Human immune Deficiency, was conducted
      from the second half of 1994 to the second half of 1996. RESULTS: The therapeutic
      changes seen on the whole seropositive population are also observed on these
      patients: the proportion of regimen with only one nucleoside analogue have
      decreased from 90.2% in 1994 to 7.5% in 1996. The proportion of treatment with
      two nucleoside analogues increased from 7.9% to 67.6%. The proportion of two
      nucleoside analogues with one protease inhibitor regimen increased from 1.9% in
      1994 to 24.6% at the end of 1996. A study focused on the second semester of 1996
      shows that the proportion of homo-bisexual patients initiating an antiretroviral
      treatment with a three antiretroviral agents combination (29.7%) is greater than
      the one in the IVDU group (20.4%) or in the heterosexual group (20.8%).
      CONCLUSION: These results show that a higher number of patient naive to the
      antiretroviral therapy initiate therapy earlier, with a two or three agents
      combination preferentially and at a better stage of immunity.

PMID- 9767853
TI  - [Fish egg poisoning (genus Barbus): experience at the Marseille and Paris Poison
      Control Centers].

PMID- 9767852
TI  - [Breast adenocarcinoma and sarcoidosis: a fortuitous association?].

PMID- 9767854
TI  - [Severe hypercorticism due to opiate withdrawal].

PMID- 9767855
TI  - [Hemobilia of gallbladder origin manifesting as malignant hypertension].

PMID- 9767856
TI  - [Inflammatory breast metastasis from cancer of the ovary].

PMID- 9767859
TI  - [Arthritis after intravesicular BCG therapy].

PMID- 9767858
TI  - [Treatment of lead poisoning].

PMID- 9767857
TI  - [Transcranial Doppler: value in the detection of right-left shunt in scuba
      divers].

PMID- 9767860
TI  - [Infectious spondylodiscitis after peridural infiltration of prednisolone].

PMID- 9767861
TI  - [The concept of therapeutic management: exemplary implementation of
      antiretroviral treatments].
AB  - Since the discover of AIDS in 1981 and the causal human immunodeficiency virus in
      1983, therapeutic strategies have gone through many phases. When the ACTG 175 and
      Delta trials demonstrated the clinical improvement offered by regiments combining
      2 nucleosides over monotherapy, combination therapy was being prescribed for less
      than 20% of all primary infections. Less than one year later, this rate suddenly
      rose to 90%. At the same time, the clinical benefit in terms of reduced morbidity
      and mortality was demonstrated for triple therapy and by the end of 1997, 65% of
      all treated HIV+ patients were taking the triple combination therapy, 34% were on
      bitherapy and only 1% on single drug regimens. This fantastically rapid evolution
      of management strategies appears even more exceptional when one realizes that
      these changes in prescription attitudes took place before expert groups were able
      to establish accepted guidelines. The number of patients under treatment also
      rose sharply from 57% in early 1994 to 87% in late 1997, while the number of
      active hospital files rose by 30%. These rapid changes in patient management
      schemes has had a major effect on HIV-related morbidity and mortality. In 1997,
      the number of deaths fell by 41% and the number of new AIDS cases by nearly 50%.
      The number of hospitalizations has also declined by 50% over the last 2 years.
      This is probably the first time in the history in medicine that preliminary
      clinical studies have led to direct patient benefit in so short a time. This
      achievement has been accomplished by the combined efforts of health care workers,
      patient associations, public authorities and the pharmaceutical industry. This
      global view must not however hide the fact that most all the prescriptions used
      today are based on the results of clinical trials in a small number of patients
      over short study periods. Long-term efficacy and tolerance remain unknown. One
      must also keep in mind one other figure which has not varied over this period.
      The percentage of new AIDS cases in patients no ith no prior treatment because
      they are unaware of the infection or because they do not want treatment remains
      unchanged at 40%.

PMID- 9767863
TI  - [Methods of investigation in pulmonary infections].

PMID- 9767862
TI  - [Pulmonary infections in immune deficiency states. Immunosuppression and its
      consequences].

PMID- 9767864
TI  - [Pulmonary infections during AIDS].

PMID- 9767865
TI  - [Pulmonary infections other than AIDS].

PMID- 9767866
TI  - [Pseudo-thrombosis of the inferior vena cava].

PMID- 9767867
TI  - [Anterior uveitis in HIV-infected patients. 3 cases in patients treated with an
      antiprotease].
AB  - OBJECTIVES: Uveitis is an ocular manifestation rarely observed in HIV-infected
      patients. We observed three cases of anterior uveitis without progressive
      retinitis in HIV patients receiving antiprotease treatment. CASE REPORT: The
      first patient developed a first episode of uveitis during ritonavir therapy. Two
      other episodes occurred with indinavir. The second patient developed uveitis when
      treated with indinavir. In the third patient, the first episode developed with
      indinavir and a second with a ritonavir-saquinavir combination. Uveitis was
      unilateral in 4 episodes. Clinical manifestations were red irritable eyes and, in
      2 episodes, reduced visual acuity. The antiprotease was interrupted in 4 of the 6
      episodes and clinical course was rapidly favorable. DISCUSSION: Pure anterior
      uveitis should suggest drug induction in HIV infected patients; rifabutin is
      often the cause. Infectious causes predominate in case of total uveitis
      associating choroid and retinal involvement. Cytomegalovirus, herpes zoster,
      syphilis, and toxoplasmosis have been incriminated. Antiproteases would appear to
      be a new cause of anterior uveitis in HIV-infected patients.

PMID- 9767869
TI  - [Leiomyosarcoma of the inferior vena cava].
AB  - BACKGROUND: The inferior vena cava is an uncommon location for leiomyosarcoma, a
      malignant tumor which develops from the smooth muscle tissue of the media. CASE
      REPORT: A 76-year-old woman was hospitalized for swelling of the lower limbs.
      Ultrasonography, computed tomography of the abdomen and magnetic resonance
      imaging showed tumoral invasion of the inferior vena cava extending to the
      atrium. Histology examination of a tumoral fragment obtained by transjugular
      catheterism affirmed the diagnosis of leiomyosarcoma. DISCUSSION: Prognosis of
      leiomyosarcoma of the inferior vena cava is very poor. No medical or surgical
      treatment has given satisfactory results. Two factors would explain the poor
      prognosis: the tumoral localization and the low degree of tumoral
      differentiation. Clinical presentation and imaging findings suggest the diagnosis
      which must be confirmed by pathology examination of a tumoral biopsy specimen.

PMID- 9767868
TI  - [The importance of lipoprotein(a) as a predictive factor of coronary
      atherosclerosis].
AB  - OBJECTIVE: The predictive value of lipoprotein(a), Lp(a), for coronary artery
      disease, is strongly suspected, though unproven. The normal serum level is 0.3
      g/l. We searched for correlations between serum Lp(a) levels and coronary artery
      disease in a population of patients hospitalized in a general cardiology unit.
      METHOD: Serum Lp(a) was assayed in all patients consecutively hospitalized during
      1994 in the Valence hospital cardiology unit. Two groups were distinguished:
      patients with coronary artery disease (n = 444) and those presumed free of
      coronary artery disease (n = 555). Coronography were performed when required.
      Serum Lp(a) levels were compared for the following variables: age, sex, smoking
      habits, blood pressure, total cholesterol, HDL and LDL-cholesterol, triglycerides
      and apolipoproteins A1 and A2. Univariate, then multivariate analysis were
      performed first patients of all ages, then for those aged more and less than 60
      years. RESULTS: Univariate analysis demonstrated that Lp(a) > 0.3 g/l was
      associated with coronary heart disease (OR = 1.33; p = 0.03), although this
      correlation was no longer significant after adjustment for other known risk
      factors (OR = 1.28; p = 0.07), except in the subgroup of patients over 60 years
      of age (OR = 1.37; p = 0.04). CONCLUSION: There was a non-significant trend
      favoring an association between serum Lp(a) level > 0.3 g/l and the development
      of coronary artery disease.

PMID- 9767871
TI  - [The major response of metastatic kidney cancer to the combination of
      oxaliplatin, 5-fluorouracil and folinic acid (FOX-FOL)].

PMID- 9767870
TI  - [Small intestine metastasis of a melanoma].

PMID- 9767872
TI  - [Cutaneous leukocytoclastic vasculitis in a patient with pulmonary tuberculosis].

PMID- 9767874
TI  - [The prescription of serum tumor markers in a general hospital].

PMID- 9767873
TI  - [Severe hypercalcemia in a patient treated with fluconazole and rifampicin].

PMID- 9767877
TI  - [Digestive disorders: improving the accuracy and safety of tests].

PMID- 9767875
TI  - [On the value of research on retinal cholesterol embolism].

PMID- 9767876
TI  - [Xenografts: clinical trials and perspectives].
AB  - Despite the reticence of certain prominent scientists, there will be no
      moratorium on clinical xenotransplantation in the USA and a limited number of
      well-controlled trials will be enabled. There has already been some advances in
      cell and tissue xenografts with encapsulated porcine pancreas cells and porcine
      foetal neurones in patients with diabetes and Parkinson's disease. However,
      because of some porcine viruses are able to develop in human tissues, current and
      planned trials have been interrupted until routine viral detection tests are
      available. Several attempts have been made in the past, with animal organs
      (kidney, heart, liver) from various non-human primate species and conventional
      immunotherapy without success. Another major question now, is the choice of the
      animal donor species. Phylogenetically dose to man, non-human primates would be a
      right and logical choice. But, because of their procurement problems, it is
      likely that most future trials will be conducted with porcine organs from more
      performant transgenic animals, more powerful immunosuppressors and new
      therapeutic strategies based on the natural tolerance mechanisms.

PMID- 9767878
TI  - [Transmission modes of hepatitis C virus].
AB  - SITUATION IN FRANCE: The prevalence of hepatitis C virus (HCV) infection in the
      French population is estimated at 1%, a level similar to that in other western
      countries. USUAL CONTAMINATION ROUTES: Epidemiological studies, together with
      gene typing, have made it possible to distinguish transmission modes. A history
      of intravenous drug abuse or transfusion is found in 60 to 80% of all subjects
      infected by the HCV. Other documented modes of contamination include
      hemodialysis, organ transplantation, accidental occupational-related puncture and
      mother-infant transmission. OTHER ROUTES: Sexual or intra-familial nonsexual
      transmission is uncommon and related to the length of exposure and the stage of
      HCV infection in the "source" subjects. Cases of HCV transmission have been
      reported during medical procedures. Currently the mode of of transmission is
      unknown in 20 to 40% of the cases.

PMID- 9767881
TI  - [Intrathoracic gossypiboma].

PMID- 9767879
TI  - [Reversible bronchial spasm syndrome in the very old].
AB  - HIGH PREVALENCE: Several epidemiological studies have shown that the prevalence
      of bronchial asthma is high in the elderly. It is often difficult to establish
      the diagnosis of asthma in this population because of the scarcity of symptoms.
      Pulmonary function tests are widely used to confirm the diagnosis. These tests
      are possible in most elderly people excepting cases of severe dementia.
      MECHANISMS: Pathophysiology of asthma in the elderly may be characterized by
      superimposition of different factors: 1) the effect of age which is associated
      with airway adrenoreceptor dysfunction; 2) the impact of chronic pulmonary
      diseases which may increase airways inflammation; 3) the role of triggers such as
      infections or various medications. MANAGEMENT: Management of asthma consists in a
      specific treatment of trigger(s) associated with anti-inflammatory and
      bronchodilator medications. Elderly subjects may have difficulty using
      offinhalators and spacer devices are widely used.

PMID- 9767880
TI  - [Surgical treatment of pulmonary metastasis of colorectal cancer. Prognostic
      survival factors].
AB  - SURVIVAL RATES: Less than 5% of patients with pulmonary metastasis from
      colorectal carcinoma will survive at 5 years, but 30% will survive at 5 years
      after surgical treatment. MAIN PROGNOSTIC FACTORS: The number of nodules,
      presence of regional lymph node metastases, disease-free interval between
      treatment of the primary tumor and development of metastasis as well as serum CEA
      level are the main prognostic discriminants. INDICATIONS FOR SURGERY: An
      aggressive operative approach is indicated even when there are pulmonary and
      extra-pulmonary localizations. Repeat thoracotomy is warranted for recurrent
      disease.

PMID- 9767882
TI  - [Acute myocardial infarction. Experiences of the referral network of the Beaujon
      and Bichat hospitals (with the collaboration of the Emergency Medical and
      Resuscitation Service of Beaujon)].
AB  - OBJECTIVES: Hospital management of acute myocardial infarction raises many
      problems in terms of medical care and organization, especially concerning the use
      or not of emergency corongraphy and angiography. We assessed the pertinence and
      consequences of a referral network operating between two cardiology units at the
      Beaujon and Bichat hospitals in Paris. All interventional procedures were
      performed at the Bichat unit. Prehospital emergency care units were integrated
      into the exprience and informed of indications for first line coronarography.
      METHODS: All cases of myocardial infarction admitted within 6 hours to the two
      units between 1993 to 1996 were analyzed and compared. RESULTS: Indications for
      referral from Beaujon to Bichat for emergency coronarography and possible
      angioplasy declined from 21% in 1993 to 10% in 1996. This decline was
      particularly noteworthy for first intention indications suggesting improved
      prehospital selection since the number of cases of acute myocardial infarction
      admitted to Beaujon remained unchanged. Certain patient characteristics differed
      between the two units: age (68.4 +/- 12.9 years at Beaujon versus 60.5 +/- 13.6
      years at Bichat in 1996, p < 0.01) and reperfusion attempts (73% versus 90% in
      1996 respectively, p < 0.01). The rate of fatal and non-fatal events were not
      different: 40 and 40% at Beaujon and 38 and 28% at Bichat in 1993 and 1996
      respectively. CONCLUSION: These findings demonstrate that a management network
      can operate effectively between two hospital cardiology units and emergency care
      structures, allowing better patient selection for emergency coronography and
      possible angioplasty.

PMID- 9767883
TI  - [Osteoarticular Mycobacterium xenopi infection].
AB  - BACKGROUND: Mycobacterium xenopi is a potential pathogen for man and can cause
      bone and joint infections, particularly spondylodiscitis. Most cases of infection
      occur in fragilized patients and are found more and more often in AIDS patients.
      CASE REPORT: A 41-year-old HIV+ woman developed cervical spondylodiscitis due to
      Mycobacterium xenopi infection. The strain was isolated from a discovertebral
      biopsy and was resistant to several antibiotics. Outcome was unfavorable.
      DISCUSSION: Most of the cases reported to date have involved spondylodiscitis of
      the thoracic or lumbar spine. To our knowledge, this is the first report of
      cervical spondylodiscitis dut to Mycobacterium xenopi in an HIV+ patient.
      Antibiotic combinations using fluoroquinolones and new macrolides are usually
      prescribed. Such protocols may provide cure of these opportunistic infections in
      immunodeficient patients.

PMID- 9767885
TI  - [Pregnancy in a patient treated with trientine dihydrochloride for Wilson's
      disease].

PMID- 9767884
TI  - [Enterobacter aerogenes pneumopathy treated by a cefepime-sulbactam-gentamicin
      combination].
AB  - BACKGROUND: Enterobacter aerogenes is the fifth most frequent pathogen causing
      nosocomial infections. Several strains have developed multiple resistance by over
      production of a natural cephalosporinase and by the presence of wide-spectrum
      betalactamases. CASE REPORT: A patient with chronic respiratory failure developed
      Enterobacter aerogenes pneumonia while under mechanical ventilation. The
      infection was successfully treated with a cefepime, sulbactam, gentamycin
      combination. DISCUSSION: Choosing the optimum antibiotic therapy is a difficult
      task in many nosocomial infections. In certain cases, combining a betalactamase
      inhibitor with the appropriate antibiotic can improve bactericidal activity and
      provide successful cure.

PMID- 9767886
TI  - [HIV arthritis: an entity apart from HIV infection].

PMID- 9767887
TI  - [A large testis disclosing a tumor of the colon].

PMID- 9767888
TI  - [Computerized prescriptions in the hospital geriatric service. Improvement of the
      precision quality of medical computers].

PMID- 9767889
TI  - [Parietal suspension during laparoscopic cholecystectomy in patients with
      respiratory insufficiency].

PMID- 9767890
TI  - [Pulmonary embolism. A development which concerns us all].

PMID- 9767891
TI  - [Pulmonary embolism. Risk factors of venous thromboembolic disease].
AB  - RISK FACTORS: Management of deep venous thromboembolism both in terms of
      diagnosis and therapeutic and prophylactic strategies has been greatly improved
      by advances in knowledge of the main acquired and intrinsic risk factors.
      RESISTANCE TO ACTIVATED PROTEIN C: This is by far the most frequent coagulation
      disorder predisposing to venous thromboembolism. Other intrinsic factors favoring
      thrombus formation (anti-thrombin II, protein C or protein S deficiencies) are
      much more uncommon. Laboratory tests in search for these anomalies are indicated
      essentially for patients who develop repeated episodes of venous thrombus
      formation. PROPHYLAXIS: Excepting specific cases, anticoagulant prophylaxis is
      not indicated in any of these anomalies beyond the usual treatment of a first
      episode. Among the risk factors for acquired deep vein thromboembolism, only
      surgery and certain obstetrical indications have been investigated sufficiently
      to define validated prophylaxis strategies. For medical risks, the benefit of
      anticoagulant prophylaxis has been demonstrated in certain disease states such as
      cancer, antiphospholipid syndrome and the acute phase of myocardial infarction
      although no widely accepted strategy has yet been established.

PMID- 9767892
TI  - [Pulmonary embolism. The role of computed tomography angiography].
AB  - NONINVASIVE PROCEDURE: Helical CT angiography is a noninvasive procedure whose
      only relative contraindications are renal insufficiency and iodine allergy.
      MASSIVE PULMONARY EMBOLISM: If a massive pulmonary embolism is suspected, helical
      CT angiography is the examination of choice because of its high accuracy in
      detecting proximal thrombi and its safety profile. NON-MASSIVE PULMONARY
      EMBOLISM: If a non massive pulmonary embolism is suspected, helical CT
      angiography, because of its high specificity, can be the first examination
      instead of scintigraphy. If a thrombus is depicted by CT, the diagnosis of
      pulmonary embolism is confirmed and treatment is started. If no thrombus is
      visualized by CT, pulmonary embolism can be ruled out in most cases. In case of
      doubt, another noninvasive procedure should be performed. Angiography should be
      the exception and seldom is needed.

PMID- 9767893
TI  - [Pulmonary embolism. Current aspects of treatment].
AB  - INDICATIONS FOR DRUG THROMBOLYSIS: There has been much debate on the indications
      for drug thrombolysis in pulmonary embolism. Thrombolysis would not appear to be
      justified excepting in massive pulmonary embolism when clinical signs or
      explorations evidence poor hemodynamic tolerance. Current data would confirm its
      independent effect on reducing mortality in such cases. MECHANICAL THROMBOLYSIS:
      The clinical efficacy of mechanical thrombolysis has not been demonstrated. It
      should not be used outside rigorously controlled clinical trials in patients with
      severe pulmonary embolism and with a formal contraindication for drug
      thrombolysis or in case of failure. THE PREPIC STUDY: The first controlled
      prospective trial on caval filters confirmed that indications for caval
      interruption in patients with proximal deep vein thrombosis should be limited to
      contraindications and failures of anticoagulant therapy. Other indications for
      filters, whether temporary or definitive, should be evaluated with specific
      controlled prospective trials. LOW-MOLECULAR WEIGHT HEPARINS: If this possibility
      is confirmed for the treatment of pulmonary embolism, it will provide a simple
      rational treatment for venous thromboembolism. 'SMALL CLOTS': Changing diagnostic
      strategies, particularly the use of helical CT angiography, has raised the
      question of therapeutic abstention when "small" clots are undetectable by this
      exploration.

PMID- 9767894
TI  - [An intragastric bridge: endoscopic extraction].

PMID- 9767895
TI  - [Ischemic colitis during colonoscopy: progression toward stenosis].

PMID- 9767896
TI  - [Dialysis in octagenarians: search for mortality risk factors. Consecutive series
      of 30 patients].
AB  - OBJECTIVE: To assess renal replacement therapy in elderly subjects aged 80 years
      or more in order to depict factors predicting mortality. PATIENTS AND METHODS: We
      retrospectively studied 30 consecutive patients at the time of starting dialysis
      from January 1995 to August 1995 and followed this population though March 1996.
      RESULTS: Only past ischemic heart disease and emergency situations were
      emphasized as predictor factors of mortality risk. No difference according to
      mortality between hemodialysis and peritoneal dialysis subgroups was found.
      CONCLUSION: Excepting usual contraindications for uremic populations, no
      objective medical criteria are at present time sufficient for excluding chronic
      renal replacement therapy in very old patients. However, its effect on quality of
      life must be estimated in order to determine the cost/benefit ratio.

PMID- 9767897
TI  - [Papillary fibroelastoma of the heart (giant Lambl excrescence). Clinical
      anatomical study on 10 surgically treated patients].
AB  - OBJECTIVES: The growing number of reports of surgery for papillary fibroelastomas
      of the heart led us to evaluate the diagnostic potential of ultrasonography in
      patients with cerebral or coronary signs and to assess the efficacy of
      anticoagulant therapy in preventing recurrent cerebral ischemia and disease
      progression after resection. PATIENTS AND METHODS: Ten cases of echographically
      diagnosed fibroelastoma of the heart treated by surgery were analyzed together
      with cases reported in the literature. RESULTS: Transesophageal echography has
      been shown to be the superior method. Surgical resection has given good results
      and the postoperative course is always excellent. Recurrent embolism occurred in
      two of our cases despite well-conducted anticoagulation. DISCUSSION: Surgical
      resection should be performed as early as possible because anticoagulation does
      not appear to sufficiently protect against embolic events, particularly cerebral
      events.

PMID- 9767898
TI  - [Peritoneal benign polycystic mesothelioma].
AB  - BACKGROUND: Benign multicystic peritoneal mesothelioma (BMPM) is an uncommon
      condition. CASE REPORT: We observed a typical case of BMPM occurring in a 57-year
      old man who presented with a painful mass of the lower right quadrant. The
      pathology using immunostaining gave the diagnosis. DISCUSSION: The diagnosis of
      BMPM can be suspected on the basis of imaging findings, but is usually confirmed
      by pathology. The only treatment for BMPM is surgical resection. Prognosis is
      good despite frequent recurrences. Two main hypotheses based on etiopathology can
      be discussed: does BMPM consist of a mesothelioma proliferative and reactional
      lesion or is it a real mesothelioma tumor?

PMID- 9767899
TI  - [Emphysematous cystitis: report of a case].

PMID- 9767900
TI  - [Late-onset pleurisy: a rare complication of thoracic radiotherapy].

PMID- 9767901
TI  - [Current problems of lead poisoning].
AB  - In collaboration with private associations and public services, we screened a
      targeted population for serum lead levels and observed lead poisoning (serum Pb >
      100 micrograms/l) in 6 out 44 children living in precarious conditions in
      Poitiers, France. This observation underscores some of the major problems
      encountered in the battle against lead poisoning in western countries. First, the
      social, economical or legal situation of the population at risk often results in
      exclusion from the normal health care network. If after a coordinated effort
      based on mutual trust, children exposed to lead poisoning can be identified, the
      second problem is to identify the source of intoxication. Scaling paint in the
      current housing may be incriminated, but how can the true source be identified
      when the populations concerned change residence often and may be unwilling to
      disclose their previous residence due to fear of reprisals for themselves or the
      new occupants? And if the source is identified, the cost of rehabilitation or the
      illegal situation of the family may raise further problems requiring adapted
      solutions. The prevention of lead poisoning calls for a targeted screening
      program, combined efforts of public authorities and health care workers, and
      close cooperation with private associations. All intoxicated children should be
      removed from the source of exposure and their families protected from the risk of
      sanctions. Only an active and practical public health policy can provide the
      solution to this continuing public health problem.

PMID- 9767902
TI  - [Digitalized conventional radiology and image network].

PMID- 9767903
TI  - [What can be expected from gene therapy in respiratory diseases?].

PMID- 9767904
TI  - [Urologic surgery and allergy to natural latex].

PMID- 9767905
TI  - [Risk factors in venous thromboembolism].

PMID- 9767907
TI  - [Evaluation of prescription of antibiotics in an intensive care unit].
AB  - OBJECTIVES: In order to optimize prescriptions, we conducted a qualitative
      evaluation of antibiotic prescription in an intensive care unit. METHODS: A
      prospective observational study was performed on 100 consecutive prescriptions
      from 11/95 to 4/96. RESULTS: Among 14 documented cases, initial antibiotic
      therapy was in accordance with antimicrobial susceptibility patterns in all but
      one case. Among 86 empirical cases, 38 were secondarily documented, yielding 43
      microorganisms. Of these 38, 27 were susceptible to 2 or more empirical
      antibiotics, 3 to only 1 and 8 to none. Antibiotics were modified in 23/38 (60%)
      cases, resulting in drug changes (n = 21) or drug addition (n = 2). In all cases,
      the new prescription was consistent with the antibiogram. In the 48 cases where
      no microorganism was isolated, antibiotic change was guided by clinical course
      and occurred in 6 (12.5%) cases. A switch to older, cheaper or more narrow
      spectrum antibiotics was possible in 18 cases, but was actually done in only 4
      (22%). Dosage errors were observed in 5 cases of initial therapy. Second line
      therapy contained 8(21%) dosage errors. Most frequently, isolated organisms at
      admission were: Staphylococcus sp. (n = 15), P. aeruginosa (n = 11) and S.
      pneumoniae (n = 10). New pathogens emerged in 16 patients (16%) receiving
      antibiotics. The most frequent was P. aeruginosa in 4 patients receiving
      ofloxacin + amoxicillin +/- clavulanic acid. CONCLUSION: These results are
      encouraging, however, the use of guidelines and periodic evaluation of antibiotic
      prescription practices might improve the efficiency of empirical antibiotic
      prescriptions and reduce overall antibiotic costs.

PMID- 9767906
TI  - [False Osler node].

PMID- 9767909
TI  - [Intermediary syndrome in acute malathion poisoning].
AB  - BACKGROUND: Acute poisoning by an organophosphorus insecticide is frequently
      observed in Morocco. We report a case of malathion poisoning complicated by an
      intermediate syndrome. CASE REPORT: A 42-year-old woman was hospitalized 3 hours
      after ingestion of 50 g of malathion. Intubation and ventilatory assistance was
      required due to failing consciousness and bronchial plugging. On day 4, a
      neurological syndrome suggestive of the intermediary syndrome with diaphragmatic
      palsy made it necessary to continue ventilatory assistance to day 20. DISCUSSION:
      The intermediary syndrome occurs 24 to 96 hours after the acute cholinergic phase
      of organophosphorus poisoning. It consists of an exclusive neuromuscular
      involvement. The intermediate syndrome is confined to an abnormality of
      neuromuscular function in specific muscle groups: proximal limb muscles, neck
      flexors, motor cranial nerves and respiratory muscles, with difficult weaning
      from respiratory assistance. The intermediary syndrome is quite uncommon. The
      risk of respiratory failure emphasizes the need for close monitoring in an
      intensive care setting for at least 96 hours, depending on the intensity of the
      cholinergic syndrome.

PMID- 9767908
TI  - [Long-term stability of bone mineral density in patients with renal transplant
      treated with cyclosporine and low doses of corticoids. Protective role of
      cyclosporine?].
AB  - OBJECTIVES: Cyclosporine has been thought to have a deleterious effect on bone in
      transplant recipients because of high turnover osteopenia observed in humans
      after transplantation. However, varying confounding factors such as renal and
      parathyroid function, cumulative steroid doses and previous exposure to
      aluminium, also play a role and hinder interpretation of the cyclosporine effect
      on bone mineral density (BMD). PATIENTS AND METHODS: A 2-year prospective study
      was conducted to measure BMD starting 3 months after transplantation and bone
      remodeling markers from the first post-transplantation day in 52 kidney
      recipients with no prior exposure to aluminum. None of the patients experienced
      rejection and at 3 months all had good stable renal function (serum creatinine
      137 mumol/l) and mildly elevated parathyroid hormone levels (1.5 times the upper
      limit of normal). All patients were given the same low dose steroid treatment (10
      mg/day) and at 6 months cyclosporine was decreased from 7 to 4.8 mg/kg/day.
      RESULTS: BMD measured by double energy X-ray absorptiometry, (DEXA) and expressed
      in Z score, was moderately decreased at 3 months for the vertebrae (-1.40), the
      femoral neck (-1.34) and the ultradistal radius (-0.95) which have predominantly
      cancellous bone and was significantly less decreased (p < 0.05) for the lower
      third of the radius (-0.6) which is mainly cortical bone. BMD measurements were
      comparable at 6, 12 and 24 months. When measured by axial computerized tomography
      (ACT) BMD of the vertebrae showed a non-significant increase of Z score from 
      1.37 to -1.19 at 2 years. Bone remodeling markers was observed up to month 6
      (from month 3 for osteocalcine and from month 1 for total and bone alkaline
      phosphatase and urinary pyridinoline), then returned to baseline levels at 2
      years in parallel with decreased cyclosporine dosage. The increase of vertebral
      BMD measured by ACT at 1 year was correlated both to cyclosporine dose at 1 year
      and to bone alkaline phosphatase at 6 months. CONCLUSION: Our data confirm the
      presence of moderate osteopenia 3 months after transplantation, predominantly in
      trabecular bone, logically linked to the initial high doses of corticosteroids.
      The long-term stability of BMD measured by DEXA and the correlation of vertebral
      BMD increase measured by ACT with cyclosporine dose and bone alkaline phosphate
      suggest that cyclosporine had a beneficial immunosuppressor effect by stimulating
      bone remodeling and thus counterbalancing the suppressive effect of
      corticosteroids.

PMID- 9767910
TI  - [BCG reactivation: a rare but specific sign of Kawasaki disease].

PMID- 9767911
TI  - [Cotrimoxazole-induced aseptic meningitis: two cases].

PMID- 9767912
TI  - [Acute levamisole poisoning].

PMID- 9767913
TI  - [Is combined statin and fibrate therapy indicated in the management of mixed
      hyperlipidemia?].
AB  - INSUFFICIENT PROGRESS: The treatment of hyperlipidemia leads to a reduced risk of
      coronary disease. This has been displayed notably since clinical trials have used
      statins. However, despite these treatments, a risk of coronary ischemia remains,
      which is not insignificant. There are several causes of this persistent risk
      which need to be analyzed. THE QUALITATIVE ASPECT OF LOW DENSITY LIPOPROTEINS:
      LDL are heterogeneous. This is displayed by a distribution of sizes varying from
      one subject to another. The predominance of small LDL is frequently found in
      coronary subjects detected during prospective or retrospective studies. The
      atherogenicity of small LDL can be explained by their physico-chemical
      characteristics. A remarkable fact is the predominance of small LDL in subjects
      with a mixed hyperlipidemia presenting a high risk of atherosclerosis. THE
      EFFECTS OF HYPOLIPIDEMIANTS: Statins greatly decrease LDL-cholesterol without
      changing LDL distribution according to size. Conversely, fibrates noticeably
      modify LDL distribution, reducing the percentage of small LDL. A PROPOSAL FOR THE
      TREATMENT OF SUBJECTS SUFFERING FROM MIXED HYPERLIPIDEMIA: If the concentration
      of LDL (reflected by LDL-cholesterol) and LDL distribution are two risk factors
      of atherosclerosis, hypolipidemic treatment should aim to act upon these two
      parameters, but no commercialized hypolipidemiant is effective enough as fas as
      they are both concerned. Therefore the combination of two hypolipidemiants, a
      statin and a fibrate, each having a predominant effect on one of the two factors,
      could be particularly effective in reducing coronary risk. This therapeutic
      association is effective on classic lipid parameters, does not entail more side
      effects than a monotherapy, and is not precluded by the RMO when there is a high
      vascular risk, which is often the case in mixed hyperlipidemia.

PMID- 9767914
TI  - [Alzheimer disease. Epidemiology, genetics and physiopathological hypotheses].
AB  - RISK FACTORS: Aging is the chief risk factor for Alzheimer's disease (AD). Other
      risk factors are aluminum in drinking water, diabetes mellitus, head trauma.
      Protective factors are: higher education, cigarette smoking, nonsteroidal anti
      inflammatory drugs and estrogen use. GENETIC FACTORS: Mutations of presenilins 1
      and 2 and of the APP gene in families with early-onset AD. Apolipoprotein E
      polymorphism in late-onset familial and sporadic AD. PATHOGENIC HYPOTHESES:
      Amyloid deposits in senile plaques and therefore dementia could be due to an
      overproduction of Abeta (Down's syndrome) or due to the primary (APP mutation) or
      secondary (role of diabetes, mellitus, apoE polymorphism: protective effect of
      estrogen) abnormal neurotoxic feature of Abeta. The hyperphosphorylation of tau
      (a protein which plays a pivotal role in the axonal transport), perhaps regulated
      by the apoE polymorphism could lead to neurofibrillar degeneration. Neurotoxic
      mediators produced by the activated microglia (perhaps activated by neuronal
      damage) and oxidative stress could also be involved in the neurodegeneration.

PMID- 9767916
TI  - [Images in medicine. Dissecting esophagitis: a rare but typical endoscopic
      aspect].

PMID- 9767915
TI  - [Alzheimer disease, markers in the cerebrospinal fluid. Support of
      physiopathologic hypotheses].
AB  - CERTAIN DIAGNOSIS: Because the certainty diagnosis of Alzheimer's disease is
      defined after autopsy or brain biopsy by the presence of neurofibrillar
      degeneration (NFD), extracellular senile plaques and vascular deposits of amyloid
      in the hippocampus amygdalus and the cerebral cortex, some authors have searched
      for biological ante-mortem markers of AD, particularly in the cerebrospinal fluid
      (CSF) which is essentially derived from brain tissue. SEARCH FOR MARKERS: Studies
      have investigated the CSF level of neurotransmitters, neuropeptides, amino acids,
      trace elements, constituents of NFD and senile plaques in a diagnostic and
      pathogenic perspective. HOPE FOR DIAGNOSIS: Even though ethical, technical and
      methodological difficulties met by authors are important and even though many
      clinical and biological parameters must be taken into account, these studies
      bring important pathogenic evidence and allow hope that markers of AD which are
      so necessary for early diagnosis and objective study of therapies will be found.

PMID- 9767917
TI  - [Images in medicine. Alveolar microlithiasis].

PMID- 9767918
TI  - [Treatment of hemophilia B with 15 nm filtered factor IX-LFB].

PMID- 9767919
TI  - [Pneumococcal infections in the adult population observed at the Poitiers
      University Hospital. Epidemiologic and clinical study].
AB  - OBJECTIVES: The aim of this study was to assess the prevalence of penicillin
      nonsusceptible pneumococcus (PNSP) infections and their clinical and
      microbiological features among an adult population hospitalized at the Poitiers
      University Hospital. PATIENTS AND METHODS: A prospective study was conducted
      between November 1994 and October 1995 and included all pneumococcus infections.
      RESULTS: Fifty-three adults with one pneumococcal strain were included. The
      overall rate of PNSP strains was 28%. Infections with PNSP strains were more
      resistant than penicillin-susceptible pneumococcus to other antibiotics. The most
      frequent infection was pneumonia (36 infections, 28% PNSP). DISCUSSION: The rate
      of PNSP in pneumococcal infections was the same in the Poitiers University
      Hospital as in national surveys in France. The high percentage of multiresistant
      strains (86.5%) limit the use of antibiotics other than beta-lactams. Surveys of
      pneumococcal resistance to antibiotics are needed to adapt antibiotic strategies
      to the local epidemiological situation.

PMID- 9767920
TI  - [Hypercalcemia associated with hyperleukocytosis, a new paraneoplastic syndrome].
AB  - BACKGROUND: The association of hypercalcemia and leukocytosis constitutes a novel
      paraneoplastic syndrome rarely reported in the course of head and neck and lung
      squamous cell carcinoma. We report 7 new cases. CASE REPORTS: In 5 cases the
      diagnosis was well-differentiated squamous cell carcinoma, in 1 differentiated
      non-small-cell carcinoma and in 1 adenocarcinoma of unknown origin. There was no
      argument favoring hyperparathyroidism in any of the cases. Microbiology tests
      were negative and large spectrum antibiotics were unsuccessful, eliminating an
      associated infection as cause of the leukocytosis. DISCUSSION: This association
      probably involves the secretion of hematopoietic growth factors such as G-CSF or
      GM-CSF by the tumor, acting simultaneously on osteoclasts and granulomonocytic
      cells which have common precursers.

PMID- 9767921
TI  - [Hereditary xanthinuria, rare cause of hypo-uric acidemia. 2 cases].
AB  - BACKGROUND: Hypouricemia can be observed in uncommon situations as in our two
      patients with hereditary xanthinuria. CASE REPORTS: In the first case, hereditary
      xanthinuria was discovered in a 36-year-old man when routine tests revealed
      hypouricemia. In the second case, a 76-year-old woman, hypouricemia was also a
      fortuitous discovery. She had major xanthinuria and a radiotranslucid lithiasis
      in the right kidney. DISCUSSION: Hereditary xanthinuria is characterized by
      hypouricemia, low urinary urate excretion and increased concentration of xanthine
      and to a lesser extent hypoxanthine. The disease results from a defect in
      xanthine oxidase and is considered to be transmitted by autosomal recessive
      heredity. This rare metabolic disorder is more often asymptomatic and detected by
      routine chemistry. Development of xanthine lithiasis is directly related to the
      low solubility of xanthine and is the main complication of the disease, occurring
      in 30-40% of patients. There is no effective treatment and the only useful
      measure is to prevent xanthine urolithiasis by maintaining urinary output above 2
      l/day.

PMID- 9767922
TI  - [Extracorporeal circulation for warming in severe accidental hypothermia. 3
      cases].
AB  - BACKGROUND: Severe accidental hypothermia with central temperature below 28
      degrees C can result from prolonged cold exposure and lead to a fatal outcome by
      spontaneous or provoked ventricular fibrillation. CASE REPORT: Three patients
      were referred for central temperature below 24 degrees C. At admission, the
      patients had major ventricular rythm disorders (two were in a state of
      circulatory arrest and the third had auricular fibrillation and circulatory
      collapse). Emergency care associated internal warning using extracorporeal
      circulation via the femoro-femoral route with a centrifuge pump. Outcome was
      favorable in 2 cases. DISCUSSION: Prognosis is very poor in patients who
      experience severe accidental hypothermia (< 28 degrees C) with circulatory
      collapse. Death often results from major rhythm disorders. Optimal emergency
      rewarming and oxygenation using extracorporeal circulatory assistance can be
      successful.

PMID- 9767924
TI  - [Pseudo-sarcoidotic lymphoma and nephrotic syndrome in a hepatitis C-carrying
      female patient].

PMID- 9767923
TI  - [Lengthened activated thromboplastin time in the course of tinzaparin therapy of
      accidental venous thromboembolism. Pilot study].

PMID- 9767925
TI  - [Nosocomial infections as indicators of quality of health care in intensive care
      units].

PMID- 9767926
TI  - [Apropos of the localization of gastric epidermoid carcinoma].

PMID- 9767927
TI  - [Drug induced lithiases].

PMID- 9767928
TI  - [Hepatitis C following kidney transplantation].

PMID- 9767929
TI  - [Medical images. Pseudo-obstruction of the small intestine].

PMID- 9767930
TI  - [Medical images. Diverticulum in the mid-third of the esophagus caused by "drug
      inclusion"].

PMID- 9767931
TI  - [Pharmocokinetics of ciprofloxacine].

PMID- 9767932
TI  - [Losing consciousness: role of the venous lactate levels in the diagnosis of
      convulsive crises].
AB  - OBJECTIVES: This prospective study was conducted to evaluate the usefulness of
      venous lactate assay in the diagnosis of generalized seizures. PATIENTS AND
      METHODS: Over a three month period, 78 consecutive adults admitted to the
      emergency unit for unconsciousness were included in the study. Three study groups
      were defined: patients with generalized seizures (n = 22), unconscious patients
      without seizure (n = 34) and known epileptic patients with unexplained malaises
      (n = 22). Patients with a disease susceptible of increasing lactate levels were
      excluded. Peripheral venous blood was drawn to determine lactates, bicarbonates
      and pH on a blood gas analyzer. All determinations were performed within 5
      minutes of blood withdrawal. CPK level was also determined with an enzymatic
      method. RESULTS: In patients who had seizures, venous lactate levels were higher
      than those in patients who had no seizures: 4.3 +/- 0.5 mmol/l in generalized
      seizure patients versus 1.64 +/- 0.1 and 2.2 +/- 1.39 in unconscious patients
      without seizure and known epileptic patients with unexplained malaise
      respectively. The threshold lactate level of 2.5 mmol/l given by ROC curves gave
      a 0.97 specificity and a 0.73 sensitivity. DISCUSSION: The acidosis observed in
      patients with generalized seizures results from the combined effects of
      respiratory and metabolic acidosis. High lactate level would be a consequence of
      hypoxemia, per seizure rise in catecholamines, and aerobic and anaerobic
      metabolism in muscles during the tonic-clonic phase. In patients presenting in an
      unconscious state, increased lactate levels, even when determined up to 2 hours
      after venous blood withdrawal, could be a useful parameter for the diagnosis of
      epileptic seizure.

PMID- 9767933
TI  - [Rapid progress of cirrhosis in hepatitis C: the role of age at the time of viral
      contamination].
AB  - OBJECTIVE: The aim of this study was to assess predictive factors for the
      progression to liver cirrhosis in hepatitis C. METHODS: One hundred thirty six
      patients (79 men; 57 women; mean age 39 years) with transfusion or intravenous
      drug use-associated hepatitis C virus (HCV) infection were studied. Sex, cause of
      infection, duration of contamination, and genotype were studied as predictive
      factors of progression to liver cirrhosis. RESULTS: One hundred twenty three
      patients presented with chronic hepatitis without cirrhosis and 13 had cirrhosis.
      At the time of liver biopsy, rates of cirrhosis were: 0% before 40 years, 10%
      between 40 and 60 years, and 47% after 60 years. (p < 0.05). Rates of cirrhosis
      according to the age at the time of contamination were as follows: 3% before 30
      years; 16% between 30 and 50 years; 46% after 50 years even though duration of
      the disease was comparable in the three groups. In multivariate analysis, two
      independent factors were associated with liver cirrhosis: age at contamination
      and duration of infection. CONCLUSION: Duration of infection and especially age
      at contamination seem better correlated with the probability of cirrhosis than
      the route of transmission or the genotype 1b. The results of this study suggest
      that progression to cirrhosis is slower in cases of contamination before 30 years
      of age than later on. Age at the time of contamination is an important predictive
      factor of progression to cirrhosis.

PMID- 9767934
TI  - [Acute arterial hypertension caused by dissecting aneurysm of the renal artery].
AB  - BACKGROUND: Aneurysm of the renal artery is an uncommon discovery at
      arteriography performed as part of a hypertension work-up. CASE REPORTS: We
      observed acute hypertension following dissection of a renal artery aneurysm which
      led to circulating channel stenosis. After surgical correction of the lesion,
      arterial pressures returned to normal. DISCUSSION: Most cases of renal artery
      aneurysm do not cause hypertension. In such cases, the high blood pressure is
      idiopathic or related to fibrodysplastic stenosis of the renal artery often
      associated with aneurysm formation. In rare cases with obstructive complications
      alone an aneurysm may lead to acute hypertension either after dissection as in
      our case or after thrombus formation. Surgery is generally required.

PMID- 9767935
TI  - [Cogan syndrome in a mature adult].

PMID- 9767936
TI  - [Aseptic osteonecrosis of the femur head in the course of rheumatoid purpura].

PMID- 9767937
TI  - [Antibodies against cytomegalovirus and risk of hepatitis C].

PMID- 9767938
TI  - [Should occupational medicine physicians be linked to future computerized medical
      record networks?].
AB  - Upcoming reforms of the health care system place high expectations on
      computerized medical file networks to control medical expenditures. In France,
      information flow from the care delivery sector to the occupational medicine
      sector is often slow or incomplete. Company and social security expenditures or
      dysfunctions as well as patient incomfort may result. An analysis of occupational
      medicine practices and the needs of physicians working in this sector leads to
      several perspective proposals for improvement including access to future
      computerized medical file networks and the health data card Sesame.

PMID- 9767940
TI  - [Prevention of diabetic nephropathies].

PMID- 9767939
TI  - [5th Conference on Opportunistic Retrovirus Infections in HIV: contribution of
      anti-retroviral combinations].

PMID- 9767941
TI  - [Type 2 endocrine neoplasms. Introduction].

PMID- 9767942
TI  - [Type 2 endocrine neoplasms. Clinical aspects].

PMID- 9767943
TI  - [Type 2 endocrine neoplasms. Genetic aspects and diagnosis].

PMID- 9767944
TI  - [Type 2 endocrine neoplasms. Prognosis and therapeutic problems].

PMID- 9767945
TI  - [Images in medicine. Rectal cancer: endoscopic-ultrasonic evaluation of the loco
      regional extension of the disease].

PMID- 9767946
TI  - [The role of ciprofloxacin in the management of chronic sinusitis].

PMID- 9767947
TI  - [Acute poisoning during substitution therapy based on high-dosage buprenorphine.
      29 clinical cases--20 fatal cases].
AB  - OBJECTIVES: Buprenorphine has been an important advance in care for drug abusers,
      but the toxic risk may be fatal. We report here two original series of
      buprenorphine poisoning in opiate abusers on substitution therapy. PATIENTS: The
      first series included 20 males and 9 females, aged 20-35 years (mean = 27.5) with
      non-fatal poisoning. The second series included 20 subjects (19 males, 1 female)
      aged 14-48 years (mean = 26.6) with a fatal outcome. All subjects were opiate
      addicts taking high-dosage sublingual buprenorphine formulation as substitution
      therapy. RESULTS: Blood concentrations of buprenorphine were found in all cases
      to remain at a low level (1.0-2.3 ng/ml, m = 1.4 ng/ml, and 1.1-29.0 ng/ml, m =
      8.4 ng/ml in non-fatal and fatal cases respectively). Almost all cases involved
      concomitant intake of psychotropic medications, especially benzodiazepines (18
      non-fatal and 17 fatal cases). DISCUSSION: These observations confirm previously
      reported data on the danger of buprenorphine-benzodiazepine combinations.
      Intravenous injection of crushed tablets also appears to be a risk factor (8
      deaths and 10 non-fatal poisonings). This series highlights the need for
      improvement in the recently developed French program for substitution therapy
      with high-dosage buprenorphine in heroin addicts.

PMID- 9767948
TI  - [Agammaglobulinemia with the absence of circulating B-lymphocytes. 9 cases].
AB  - OBJECTIVES: Agammaglobulinemia with absence of circulating B lymphocytes is a
      rare genetically transmitted immunodeficiency that appears in early childhood and
      affect mainly boys. The clinical manifestations of the disease are rather
      heterogeneous. PATIENTS AND METHODS: Nine patients (7 boys and 2 girls) were
      diagnosed as suffering from agammaglobulinemia with absence of circulating B
      lymphocytes, over a period of 6 years. Quantitation of immunoglobulins and search
      for circulating B lymphocytes were respectively performed by the Mancini method
      and immunofluorescence using T specific (anti-CD3, anti-CD4 and anti-CD8) and B
      (anti-CD19) monoclonal antibody. RESULTS: The disease started to manifest
      clinically at the mean age of 8.7 months (4-16 months). The mean age at diagnosis
      is 4 years (1-11 years). The clinical manifestations were essentially recurrent
      infections of the lung and the gastrointestinal tract. However, bacterial
      meningitidis was observed in 3 patients. Severe complications such as an
      echovirus 27 meningoencephalitis and a chronic active hepatitis (1 patient) and a
      pericarditis (1 patient) were observed. All of our patients lacked circulating B
      lymphocytes and had low or null immunoglobulin levels. Five patients were treated
      by intravenous immunoglobulin (Ig) and 3 were treated by intramuscular
      immunoglobulin with a residual IgG level respectively of 5.5 g/l and 3.3 g/l.
      CONCLUSION: Recurrent infections are the principal manifestation of the
      agammaglobulinemia, early Ig treatment is the only therapy allowing improved.

PMID- 9767949
TI  - [Tamponade in patients with systolic left ventricular dysfunction. An atypical
      presentation].
AB  - BACKGROUND: Left ventricular failure has been described following surgery due to
      localized compression of the left ventricle and in case of diastolic left
      ventricular dysfunction after pericardiotomy or pericardiocentesis. CASE REPORTS:
      Global heart failure was observed in 3 patients with dilated cardiopathy who
      developed tamponade. Systolic left ventricular dysfunction was caused by ischemic
      heart disease in one patient and secondary to anthracyclin chemotherapy in the
      two others. The effusion was successfully removed with pericardiocentesis in all
      three cases. No specific complications were observed. DISCUSSION: Although
      exceptional, tamponade may occur in patients with signs of left ventricular
      failure.

PMID- 9767951
TI  - [Acute ulceration of the vulva during a primary Epstein-Barr virus infection].

PMID- 9767950
TI  - [Hypovitaminosis K during treatment with doxycycline].

PMID- 9767953
TI  - [Prohibition of human cloning. The status 1 year after the Scottish experience].

PMID- 9767952
TI  - [Cushing syndrome: a secondary cause of osteoporosis not to be ignored].

PMID- 9767954
TI  - [The National Academy of Medicine. Hospital nursing courses during the 1st four
      years of medical studies].

PMID- 9767955
TI  - [Gene therapy in rheumatoid polyarthritis: perspectives].
AB  - THE CONCEPT OF GENE THERAPY: Gene therapy is applicable in diseases involving
      several genes such as rheumatoid arthritis. Gene transfer is the insertion in
      vivo of genetic material necessary to produce a molecule with therapeutic action.
      This strategy is currently in experimental stages; feasibility studies in humans
      are in the preliminary stage. SEVERAL TARGETS: In experimental models of
      rheumatoid arthritis, the most widely studied target genes are those which code
      for inflammation inhibitors such as IL-1 receptor antagonists or anti
      inflammatory cytokines (IL-4, IL-10, IL-13). Another interesting target would
      concern genes coding for molecules inhibiting joint destruction (for example
      metalloprotease inhibitors). VECTORS: The development of high-performance vectors
      (both viral and nonviral vectors) will greatly improve the expected benefit/risk
      potential of gene therapy in general. IN RHEUMATOID ARTHRITIS: The particular
      problem in rheumatoid arthritis is the choice of the transfection site. An
      articular site would require multiple injections in the different affected
      joints. A systemic approach would take into account the general disseminated
      nature of the disease.

PMID- 9767956
TI  - [Pneumococci with diminished sensitivity to penicillin in pneumopathies. Clinical
      consequences].
AB  - INCREASING PREVALENCE: Since 1988, French clinicians have been faced with an
      increasing prevalence of penicillin-resistant pneumococcal pneumonia. In 1996,
      the percentage of strains with reduced susceptibility to penicillin reached more
      than 40% and the number of multiresistant strains has increased steadily.
      CLINICAL IMPACT: Despite this apparently alarming situation, the clinical impact
      is not obvious. Different clinical studies have demonstrated that mortality due
      to pneumococcal pneumonia has not been affected by the development of resistant
      strains, eventually because the strains involved belong to less invasive
      serotypes than penicillin susceptible pneumococci. HYPOTHESIS: The preferential
      distribution of penicillin resistance among less invasive serotypes might explain
      the development of resistance in carriage strains more often exposed to
      antibiotic selection and the greater risk for immunodepressed subjects to acquire
      these strains. PRACTICAL CONSEQUENCES: To date, first-line antibiotic therapy
      with amoxicillin at the dose of 3g/24 h remains valid for the great majority of
      cases. Use of much higher dosages or other antibiotics for pneumococcal pneumonia
      would only be rational when penicillin minimum inhibitory concentrations are
      above 2 mg/l.

PMID- 9767957
TI  - [Pouchitis after ileo-anal anastomosis with a reservoir in hemorrhagic
      rectocolitis].
AB  - DEFINITION AND FREQUENCY: An ileoanal anastomosis with creation of an ideal pouch
      is proposed as the treatment for familial adenomatous polyposis and ulcerative
      hemorrhagic rectocolitis. The ideal pouch may become inflammatory in 10 to 30% of
      the cases. The diagnosis of pouchitis is based on a clinical, endoscopid and
      histological criteria. PATHOGENIC HYPOTHESES: Pouchitis is a late complication,
      mainly after ileoanal anastomosis for ulcerative rectocolitis. The pathogenic
      mechanism is a subject of debate. Fecal stasis, bacterial pollution, mucine
      secretion and the underlying inflammatory disease could be involved. TREATMENT:
      Antibiotics active against anaerobic bacteria, such as metronidazole, are
      generally given. In case of failure, common antiinflammatory agents used in
      inflammatory bowel disease are indicated.

PMID- 9767958
TI  - [Millimetric choledochal calculi, diagnosis using echo-endoscopy].

PMID- 9767959
TI  - [The role of ciprofloxacin in the treatment of chronic bronchitis].

PMID- 9767960
TI  - [Demonstration of the sentinel lymph node in axillary dissection for breast
      cancer].
AB  - OBJECTIVES: The sentinel node is defined as the first-line axillary lymphatic
      drainage node in breast cancer. If the sentinel node can be identified, during
      axillary dissection for breast cancer, resection could be limited reducing
      subsequent morbidity. However, before modifying the standard dissection
      procedure, it is important to prove that the sentinel node is representative of
      the metastatic status of other axillary nodes. PATIENTS AND METHODS: Between
      March and December 1996, 86 patients (mean age 58 years, range 32-82) underwent
      amputation (n = 20), tumorectomy with dissection (n = 56) or tumorectomy followed
      by secondary dissection (n = 10) for breast cancer. Ten ml of diluted patent blue
      was injected either into the peripheral portion of the tumor or the tumorectomy
      cavity. Node dissection was performed 10 to 20 minutes after injection. The blue
      sentinel node was identified prior to standard dissection. RESULTS: A mean 12
      nodes were removed (range 4-21). Seventy-nine sentinel nodes were identified
      (91%) and in 7 cases (8%) a sentinel node could not be identified. In 7 other
      cases the sentinel node was a false negative, i.e. non malignant despite
      metastases in other dissected nodes. In all the other cases, the status of the
      sentinel node predicted the status of the other nodes, i.e. a non-metastatic
      sentinel node associated with other metastatic nodes. Finally, in 7 cases, the
      sentinel node was the only invaded node among the nodes dissected. During the
      last 3 months of the study, the sentinel node was identified in 100% of the cases
      and was representative of the overall dissection. CONCLUSION: Identifying the
      sentinel node is an alternative to standard axillary node dissection procedures.
      The method requires a training period and identification can be improved with
      radioimmunologic guidance. Patient selection within the framework of a rigorous
      multidisciplinary protocol is indispensable. A nationwide study is currently
      being conducted to validate these preliminary results.

PMID- 9767962
TI  - [Undifferentiated embryonal sarcoma in the liver of adults].
AB  - BACKGROUND: Embryonic sarcoma of the liver is uncommon in adults. We report an
      unusual case presenting as a cyst-like formation of the liver. CASE REPORT: The
      pre-operative and also the peroperative histology diagnosis was remodelled
      biliary cyst. The patient was treated accordingly. The final diagnosis of
      embryonic sarcoma of the liver was made when a local recurrence developed. The
      patient underwent hepatic resection followed by a chemotherapy and radiotherapy
      protocol. Tumor markers were measured within the tumor and gave a positive result
      for CA-125. DISCUSSION: Diagnosis of cystic forms of embryonic sarcoma can be a
      quite difficult task. Radiological and histological aspects can be helpful. This
      report is the first case in which tumor markers were measured within the tumor.

PMID- 9767961
TI  - [Is there a correlation between dietary habits and hemorrhoidal disease?].
AB  - OBJECTIVES: It is empirically accepted that certain foods play a role in the
      pathogenesis of hemorrhoids or their acute exacerbation. The aim of this work was
      to determine whether there is a relationship between hemorrhoids and certain food
      related or common toxin-related factors. PATIENTS AND METHODS: Two groups of 50
      subjects were compared. Group I was composed of 50 patients with hemorrhoid
      symptoms. Fifty volunteers with no proctologic abnormality were included in group
      II. We used a diet survey to compare total calorie, protein, carbohydrate, fat,
      food fiber, water, alcohol, salt, pepper, pimento, tea, and coffee intake was
      well as smoking habits. Episodes of constipation were also noted. RESULTS:
      Overall calorie intake, as well as protein, carbohydrate and fiber intake were
      similar in the two groups as were use of salt, coffee and tea. Dietary intake in
      group I was higher for fat (p = 0.02), alcohol (p = 0.01), pepper (p = 0.04, and
      pimento (p = 0.001). Subjects in group I drank less water (p = 0.008), smoked
      more (p = 0.01) and were more often constipated (p < 0.001) than those in group
      II. CONCLUSION: Our findings provide further arguments suggesting that dietary
      imbalance or smoking could be involved in the development of hemorrhoids. These
      factors should be evaluated in appropriate dietary inquiries. Epidemiological
      surveys would be required to confirm their possible causal effect.

PMID- 9767963
TI  - [Septic arthritis in AIDS. 10 cases].

PMID- 9767964
TI  - [Appendiceal syndrome disclosing Behcet disease].

PMID- 9767966
TI  - [Evaluation criteria of multimedia teaching materials in medicine].

PMID- 9767965
TI  - [Plasmodium falciparum malaria: type R1 resistance to quinine in west Africa].

PMID- 9767967
TI  - [Adenocarcinoma of the pancreas].

PMID- 9767968
TI  - [Adenocarcinoma of the pancreas. General characteristics].
AB  - EPIDEMIOLOGY: Pancreatic carcinoma ranks fifth among the leading causes of cancer
      death in developed countries. Although the incidence of pancreatic cancer is
      about 10 per 100,000 inhabitants, the five-year overall survival is barely one to
      4%. Few risk factors have been identified. Smoking increases the relative risk by
      1.5, chronic pancreatitis by 26. Hereditary formes are rare. PATHOLOGY AND
      MOLECULAR ABNORMALITIES: Adenocarcinomas of the ductal phenotype represents about
      90% of the pancreatic tumors. Seventy percent of adenocarcinomas are located in
      the head. Mutations of K-ras oncogene and p53 anti-oncogene are noted,
      respectively, in 80 to 90% and 70% of the ductal adenocarcinomas. The mutation of
      p53 is associated with a poor prognosis. Certain less frequent forms such as
      mucinous cystadenocarcinomas, or intraductal papillary-mucinous tumors seem to
      have a better prognosis. However, this is not true for acinar cell carcinomas
      responsible for various paraneoplastic syndromes. PATTERN OF SPREAD: The disease
      arises in the ductal epithelium and rapidly spreads to regional lymph nodes and
      the liver. At diagnosis, nodal involvement is found in 80% of cases. Half of the
      patients have detectable visceral metastasis with a median survival of three to
      six months. Among the remaining non metastatic patients, approximately one in 5
      has undetected peritonal carcinomatosis. Only 10 to 20% of the patients undergo
      surgical complete resection with a median survival of 15 to 19 months.

PMID- 9767969
TI  - [Adenocarcinoma of the pancreas. Diagnosis and evaluation].
AB  - SYMPTOMS: Pain, jaundice, or weight loss are the presenting features of 90% of
      the cases. Patients with tumors of the body or the tail of the pancreas do not
      rapidly develop jaundice. Therefore, their diagnosis is delayed and metastasis
      are more frequently detected at diagnosis. RADIOLOGIC DIAGNOSIS: The diagnosis
      may be established by ultrasonography, endoscopic ultrasonography and most
      importantly by CT scan with helicoidal continuous acquisition and contrast
      injection. However, these methods do not efficiently detect tumors smaller than 2
      cm or with only superficial peritoneal involvement. Laparoscopy and angiography
      are used less and less frequently to evaluate resectability. The diagnostic work
      up with CT scanning is able to anticipate resectability in 50 to 90% of the
      cases. PATHOLOGY: Histopathology must be obtained since 10% of the pancreatic
      carcinoma are not of the ductal type and not all pancreatic tumors are malignant.
      When a pathological specimen cannot be obtained during surgery, a cytology
      specimen may be obtained with a fine needle guided by CT scan. PROGNOSIS:
      Survival depends on the possibility of a complete resection of the tumor. If
      complete resection is obtained, the prognostic factors are in decreasing
      importance: tumor size, lymphatic and vascular involvement, and invasion of peri
      pancreatic tissues.

PMID- 9767970
TI  - [Adenocarcinoma of the pancreas. Therapeutic strategies].
AB  - SURGERY: Surgery whether curative or palliative, is the major modality of
      treatment. A complete resection is possible in about 20% of patients with a
      median survival of 12 to 16 months and a 20% five year survival. After complete
      resection 70 to 80% of patients develop a local recurrence. Biliary and gastro
      intestinal bypasses as well as antalgic techniques are useful palliative
      procedures. ADJUVANT AND NEOADJUVANT TREATMENT: Chemoradiotherapy is used either
      as adjuvant or neoadjuvant treatment. External beam irradiation techniques are
      used to deliver 45 to 50 Gy to the pancreas in five to six weeks. Concomitant
      fluorouracil is administered in bolus injections or better in continuous
      infusion,, either alone or in association with cisplatinum. Chemoradiotherapy
      reduces the local relapse rate and slightly, though significantly, increases the
      median survival. Therefore, after chemoradiotherapy, metastatic spread becomes
      the major cause of death. PALLIATIVE TREATMENT: For locally advanced diseases,
      chemoradiotherapy has a true palliative effect with acceptable toxicity.
      Metastatic disease remains a challenge. Fluorouracil based chemotherapy with or
      without cisplatinum occasionally obtains effective palliation. Among new agents,
      only gemcitabine has proven clinical activity associated with low toxicity and is
      practical to use. THERAPEUTIC STRATEGY: Presently, patients with resectable
      pancreatic carcinoma should be included in a prospective trial to receive
      combined modality treatment with adjuvant or neo-adjuvant chemoradiotherapy. The
      choice of treatment for patients with locally advanced or metastatic disease,
      should be based on the possibility of assuring a satisfactory quality of life.
      Present research should progress through controlled clinical trials to study
      original systemic treatment and combined modalities able to produce a lasting
      local control.

PMID- 9767971
TI  - [Bacteriology in community-acquired respiratory pathology].

PMID- 9767974
TI  - [Acute hepatitis due to ecstasy].
AB  - BACKGROUND: Ecstasy is a synthetic amphetamine which causes a wide variety of
      adverse effects. Hepatic toxicity was only recently demonstrated but can be quite
      severe. CASE REPORT: A 27-year-old male with no past medical or surgical history
      developed jaundice without fever. He was a regular user of ecstasy and had
      recently increased the number of doses consumed. No evidence of a viral,
      alcoholic, metabolic or autoimmune mechanism was found which could explain the
      hepatitis. Complete cure was obtained by discontinuing ecstasy. DISCUSSION: Few
      cases of ecstasy hepatic toxicity have been reported. Ecstasy was undoubtedly the
      causal agent in this case since other known causes of acute hepatitis were
      excluded, confirming the hepatotoxicity of ecstasy reported in the literature.
      The liver disease has been reported to range form acute regressive hepatitis to
      fatal liver failure. Iterative exposure can lead to fibrosis. The
      pathophysiological mechanism of this toxic effect is not well elucidated.
      Ischemia alone cannot explain all the clinical forms described, particularly
      cases without hyperpyrexia. Ecstasy must be added to the list of potential causes
      of acute hepatitis. Exposure must always be searched for in cases of acute
      hepatitis in young subjects.

PMID- 9767972
TI  - [Gammopathies of indeterminant significance and osteoporosis: association or
      coincidence?].
AB  - OBJECTIVES: Osteoporosis is common in subjects over 70 years of age. Likewise,
      the incidence of monogammapathies of undetermined signification (MGUS) increases
      with age. We conducted this study to determine whether the biological and
      histomorphometric characteristics of osteoporosis in patients with MGUS are
      different from those in primary osteoporosis and to ascertain whether any cause
      and effect relationships could exist between MGUS and osteoporosis, excluding
      signs of active myeloma. PATIENTS AND METHODS: Serum and urinary phosphorus and
      calcium, histomorphometric measurements, hormone levels and serum cytokines (IL1,
      IL6 and TNF alpha) were determined in 7 patients (mean age 71.8 years, 2 men and
      5 women) with MGUS associated with osteoporosis with vertebral fractures (OP) and
      compared with those in 7 osteoporosis patients without MGUS matched for age, sex,
      and osteoporosis severity and 7 other age and sex matched patients with MGUS
      without OS. The MGUS + PS patients were followed for 9 years (4.5 to 20) so
      slowly progressive myeloma could be excluded. RESULTS: Cytokine levels were the
      same in the three groups of patients but MGUS + OP patients had higher urinary
      calcium levels (ca/cr = 0.21 +/- 0.08 vs 0.12 +/- 0.1 (OP) and 0.13 (MGUS); p =
      0.04), decreased osteocalcin levels (7 +/- 4.6 ng/ml vs. 12 +/- 4 (OP) and 11.5
      +/- 5 (MGUS); p = 0.01) and increased surface resorption (8 +/- 1.4 vs. 3.6 +/-
      1.2 (OP) and 5.5 +/- 1.7 (MGUS); p = 0.05). DISCUSSION: It has been demonstrated
      that MGUS in patients with increased resorption and lower osteocalcin levels
      frequently progresses to active myeloma. The question is raised as to whether, in
      certain cases of MGUS, in situ stimulation of bone cells by monoclonal plasma
      cells could exist without ongoing transformation to active myeloma.

PMID- 9767973
TI  - [Nephritic colic due to indinavir].
AB  - OBJECTIVE: Evaluate the frequency and assess curative and preventive measures
      against urinary lithiasis in patients treated with indinavir. PATIENTS AND
      METHODS: Fourteen HIV seropositive patients who developed severe and acute flank
      pain were included. Four of the patients receiving 800 mg indinavir t.i.d. had
      fever (38.5 degrees C) or delayed secretion (> 2 h). Delay from indinavir
      treatment onset was 1 to 321 days. During the same period, 155 patients had been
      treated with indinavir. Clinical features, radiology and laboratory results were
      recorded in addition to an analysis of the lithiasis if possible. RESULTS:
      Transient moderate renal failure occurred in 8 patients. Mean urine pH was 6.
      Serum phosphorus, calcium, and uric acid, liver tests and urinalysis were normal.
      A JJ ureteral stent was inserted in 4 cases due to complications. In all cases,
      fluids, analgesics and antispasmodics provided favorable outcome. Inversely,
      nonsteroid antiinflammatory drugs given in 2 patients had a deleterious effect on
      renal function. The lithiasis was eliminated in 3 cases and infrared
      spectrophotometry demonstrated a structure compatible with indinavir monohydrate.
      CONCLUSION: The formation of urinary lithiasis is a frequent complication of
      indinavir therapy (9%). Hyperhydration and urine acidification are usually
      successful but emergency drainage is required in approximately 3% of cases.
      Nonsteroidal antiinflammatory drugs should be avoided due to the risk of renal
      toxicity. A precise evaluation of fluid intake and diet, drug associations and
      personal history is needed to recognize patients at risk of recurrent lithiasis
      formation.

PMID- 9767975
TI  - [Descending necrotizing mediastinitis. A diagnosis not to be ignored].
AB  - BACKGROUND: Acute descending posterior mediastinitis is a very serious condition
      which can develop after common ear-nose-throat infections. Clinical
      manifestations are typical and must be recognized rapidly for early diagnosis.
      CASE REPORTS: We report two cases. In the first case, a 28-year-old man had a
      retropharyngeal abscess which fistulized into the left pleural cavity. Three
      operations were necessary to achieve cure and favorable outcome. In the second
      case, mediastinitis was diagnosed in a 39-year-old patient following a throat
      infection. Despite early surgery, outcome was fatal due to development of
      pericarditis and tamponnade. DISCUSSION: These two cases illustrate the variable
      course of descending mediastinitis and emphasize the importance of early
      medicosurgical cure. Treatment is based on intravenous antibiotics using a
      combination of 2 or 3 drugs at high doses in association with emergency surgery
      and extensive mediastinal washings. Despite well-conducted treatment, descending
      necrotizing mediastinitis may lead to a fatal outcome.

PMID- 9767976
TI  - [Reactive lymphadenopathy to wear debris of the hip prosthesis. Differential
      diagnosis of pelvic lymphatic metastasis].

PMID- 9767978
TI  - [Acute oligo-arthritis in a patient treated with BCG therapy for bladder
      carcinoma].

PMID- 9767977
TI  - [Subclinical cortisol-secreting adrenal adenoma. Follow-up over 5 years].

PMID- 9767979
TI  - [The elderly in need].

PMID- 9767980
TI  - [Acceptability and short-term tolerance to an orally administered new formulation
      of magnesium (TX 1341) compared to that of a reference magnesium].

PMID- 9767981
TI  - [Urinary incontinence in very elderly persons: health education improves access
      to health care].

PMID- 9767982
TI  - [Ramadan: the problem of tobacco].

PMID- 9767984
TI  - [Anti-pneumococcal vaccination in elderly persons].

PMID- 9767983
TI  - [Inflammation and joint destruction during rheumatoid polyarthritis: what
      relation?].
AB  - A QUESTION REVISITED: It is generally accepted that acute then chronic joint
      inflammation leads to the development of a synovial pannus and secondarily to
      characteristic degenerative joint disease en rheumatoid arthritis. However
      accumulating clinical and biological evidence would question the real
      relationship between inflammation and joint destruction, and suggest therapeutic
      strategies might need to be revisited. THE CAUSAL EVENTS: Synovial proliferation
      is the fundamental event in joint lesions. The contact between the synovial
      pannus and the cartilage leads to characteristic joint damage mediated by pro
      inflammatory cytokines (TNF alpha and IL 1) and enzyme secretion, particularly
      metalloproteases. ROLE OF T CELLS: The role of T-lymphocytes is a question of
      much debate. Although it is generally accepted that T cells are crucial in the
      initial phases of rheumatoid arthritis, several arguments suggest that the
      process of synovial proliferation and joint destruction in advanced stage disease
      would be independent of T cell activity. Synovial macrophages and fibroblasts,
      and perhaps chondrocytes, play a central role at this phase. THERAPEUTIC
      IMPLICATIONS: A direct mandatory relationship between inflammation and joint
      destruction appears to be excluded, although complex and poorly understood links
      exist between these events in rheumatoid arthritis. A better understanding of the
      mechanisms involved would be very useful for the development of more adapted
      therapeutic strategies in rheumatoid arthritis.

PMID- 9767986
TI  - [Cardiorespiratory effects of laparoscopic surgery].

PMID- 9767985
TI  - [Primary pulmonary arterial hypertension].

PMID- 9767987
TI  - [Severe gastrointestinal hemorrhages].

PMID- 9767988
TI  - [Ambulatory surgery in children: practical aspects for the anesthetist].

PMID- 9767989
TI  - [Postoperative thromboembolic disease. Prevention, diagnosis, treatment].

PMID- 9767990
TI  - [Rules of preoperative antibiotic prophylaxis prescription].

PMID- 9767991
TI  - [Malignant anesthesia hyperthermia].

PMID- 9767992
TI  - [Preoperative management of subjects at risk].

PMID- 9767993
TI  - [Preoperative management of subjects at risk. Asthmatic patients].

PMID- 9767994
TI  - [Preoperative management of subjects at risk. Diabetic patients].

PMID- 9767995
TI  - [Preoperative management of subjects at risk. Obese patients].

PMID- 9767996
TI  - [Extrapulmonary tuberculosis in the central western region. Retrospective study
      of 217 cases (Gericco 1991-1993)].
AB  - OBJECTIVES: To analyze the epidemiological, clinical and diagnostic
      characteristics of extrapulmonary tuberculosis in western France observed from
      1991 to 1993 in different patients populations (HIV+ infected patients,
      immunosuppressed non-HIV infected patients, non-immunosuppressed patients) and
      according to various localizations (lymph nodes, bone and joints, genital organs,
      nervous system and meninges, miliary disease). METHODS: This retrospective study
      included 217 cases of extrapulmonary tuberculosis diagnosed from 1991 to 1993 in
      western France by GERICCO (Groupe d'Epidemiologie et de Recherche en
      Infectiologie Clinique du Centre-Ouest). Demographic, clinical, biological,
      microbiological and radiographic characteristics as well as clinical course on
      specific therapy were assessed. RESULTS: Extrapulmonary tuberculosis generally
      occurred most often in immunosuppressed patients but 34% of cases were observed
      in people without any underlying disease or risk factors. Delay to diagnosis was
      especially long in the non-immunosuppressed patients (mean = 96 days) but shorter
      in the HIV-infected patients (mean = 59 days). It was shorter in case of nervous
      system involvement (mean = 52 days) or military disease (mean = 80 days) than in
      bone and joints (mean = 120 days) and lymph nodes (mean = 102 days).
      Microbiologically proven tuberculosis represented only 75% of cases despite
      numerous investigations. Overall prognosis was good except in nervous system and
      meninges localizations. Failures were mainly due to death in immunosuppressed
      patients. CONCLUSION: Extrapulmonary tuberculosis remains frequent even in
      patients lacking risk factors. In 50% of cases, confirmation of diagnosis takes
      more than one month. In case of doubt, clinicians should not wait for laboratory
      results before implementing empirical specific therapy.

PMID- 9767997
TI  - [Ambulatory surgery in French public hospitals. Present and future. "Public
      hospitals" group of the French Association of Ambulatory Surgery].
AB  - OBJECTIVES: To assess ambulatory surgery practices in France, make an inventory
      of projects for the creation of ambulatory structures and analyze the perception
      of different hospital personnel of ambulatory surgery. METHODS: A questionnaire
      was sent to 541 public hospitals with a surgery unit in France. The first part of
      the questionnaire was used to record current activity and existing projects for
      ambulatory surgery. The questionnaire also collected opinions concerning the
      analysis of difficulties encountered and possibilities offered by ambulatory
      surgery. RESULTS: Overall participation rate was 59%. Ambulatory surgery was
      practised in 81% of the hospitals. Sixty-six percent had a projects under
      consideration, including several at the decision making stage (17%). 1550
      ambulatory surgery clinics could be created by the year 2000. In 66% of the
      cases, the future facility would be integrated into the traditional surgery unit.
      There was favorable opinion concerning the development of ambulatory surgery
      clinics in public hospitals in 83% of the cases. Inconveniences suggested
      generally involved organizational aspects, particularly concerning medical
      organization. Foreseen obstacles to the development of ambulatory surgery clinics
      were regulatory procedures, unfavorable exchange rate, insufficient investment
      funds and the lack of a policy favoring their development. CONCLUSION: The
      development of ambulatory surgery clinics in public hospitals in France can be
      expected in the near future. Budgeting and regulatory procedures must however be
      adapted to promote implementation of the existing projects.

PMID- 9767998
TI  - [Late manifestation of common variable immunodeficiency by Biermer's disease].
AB  - BACKGROUND: Common variable immunodeficiency (CVI) is a heterogeneous disorder
      characterized by decreased production of antibodies. Clinical presentation of CVI
      is generally that of recurrent pyogenic infections. Autoimmune diseases can also
      occur. The age of onset of symptoms shows two peaks at 1-5 and 16-20 years. CASE
      REPORT: A 77-year-old man was admitted in hospital for pernicious anemia. We
      discovered hypogammaglobulinemia with low levels of immunoglobulin G, A and M,
      but normal T-cell levels. We diagnosed common variable immunodeficiency. This
      patient had not had recurrent pyogenic infections. DISCUSSION: This case shows
      that common variable immunodeficiency can be revealed late by an autoimmune
      disease. The pathogenesis of autoimmune diseases in this immunodeficiency remains
      unknown despite several possible explanations.

PMID- 9768000
TI  - [Campylobacter fetus endocarditis manifested by a popliteal mycotic aneurysm].
AB  - BACKGROUND: Campylobacter fetus endocarditis is uncommon and may be life
      threatening. CASE REPORT: A 91-year-old patient with rectal villous
      adenocarcinoma was admitted with fever and recent complaints of popliteal pain.
      The definite diagnosis of endocarditis and mycotic aneurysm related to C. fetus
      infection were accepted on the basis of clinical, radiological and
      microbiological data. Cure was achieved with antibiotics and surgery of the
      aneurysm without valvular replacement. DISCUSSION: C. fetus endocarditis was
      probably secondary to the iterative laser treatment of the rectal tumor that had
      been performed during the past weeks without antibiotic prophylaxis.

PMID- 9767999
TI  - [Value of magnetic resonance cholangiography in the diagnosis of common bile duct
      cystic dilation].
AB  - BACKGROUND: Magnetic resonance cholangiography is a noninvasive method for
      exploring the biliary and pancreatic ducts. Allergic risk is reduced as no
      contrast agent is required and there is no risk of infectious contamination due
      to catheterism. Unlike endoscopic retrograde cholangiography which requires
      anesthesia, there is no risk of morbidity. We report one observation of Todani
      type Ia cystic dilation of the main bile duct explored preoperatively with MR
      cholangiography. CASE REPORT: A 39-year-old woman complained of acute abdominal
      pain. Physical examination revealed jaundice and fever. MR-cholangiography gave
      the diagnosis of angiocholitis with cystic dilatation of the main bile duct (type
      Ia). Surgery was indicated. The procedure included a Y-loop hepato-jejunal
      anastomosis and cholecystectomy. The postoperative period was uneventful.
      Pathology reported a cystic formation with no signs of malignancy. DISCUSSION:
      Common manifestations of congenital cystic dilatation of the main bile duct are
      biliary pain, fever and jaundice. The MR-cholangiogram provides a map of the bile
      duct system directly with a noninvasive procedure. The map may be obtained in
      several planes to guide surgery. Indeed, since cholangiocarcinoma is found in
      numerous cases, surgery is a formal indication in patients with angiocholitis.

PMID- 9768001
TI  - [Palinopsia in Charles Bonnet syndrome].

PMID- 9768002
TI  - [Laparoscopic adrenalectomy in pheochromocytomas].

PMID- 9768003
TI  - [Weak antiviral effect of changing two nucleoside analogues combined with
      antiretroviral agents. 3TC and d4T after ZDU and ddi or ddc].

PMID- 9768004
TI  - [Fragility of scientifically acquired data. The example of fluoride salts in
      osteoporosis].
AB  - Although there is a pathophysiological rationale for the use of sodium fluoride
      for the treatment of postmenopausal osteoporosis and a long history of clinical
      trials, there is no evidence today of its clinical efficacy. The use of sodium
      fluoride was a long-standing practice for many years which became official policy
      when strong scientific arguments suggested its efficacy. The lack of
      methodologically solid evidence however raised some doubts, echoed by the
      regulatory authorities, and led to a re-evaluation. The unacceptable risk/benefit
      ratio demonstrated by the new results was a major scientific event giving the
      scientific community a concrete example of why evidence provided by clinical
      research must be regularly revisited.

PMID- 9768005
TI  - [Medicine of care as seen by Cuvier in 1808].

PMID- 9768006
TI  - [Genomic imprinting].
AB  - AN EXCEPTION TO THE RULE: For certain genes, alleles are expressed differently
      depending on whether they originate from the maternal or paternal genome. This is
      called the parental imprinting. The parental imprinting plays an important role
      in development and a dysregulation can lead to various disease states. Loss of
      the parental imprinting or its alteration is implicated in certain genetic
      diseases and cancers. When the process is altered, two homologous chromosomes may
      come from the same parent, a situation termed uniparental disomy. GENETIC DISEASE
      IN MAN: Several genetic diseases in man are known to be related to the parental
      imprinting. Willi-Prader disease, Angelman disease and Beckwith-Wiedemann disease
      are the most extensively studied. MECHANISMS: Some of the underlying mechanisms
      are known, but several points concerning the parental imprinting remain to be
      elucidated, particularly the precise nature of the molecular mechanisms and the
      identification of the genes controlling this genetic process.

PMID- 9768007
TI  - [Diagnosis and management of parasitic hypereosinophilia].
AB  - ETIOLOGY: Helminth infestation of the digestive tract or organ tissues is a
      common and curable cause of high eosinophil counts. Parasite infestation should
      be the number one suspect in patients with hypereosinophilia. DIAGNOSIS: Clinical
      signs and epidemiology are suggestive. If the patient has travelled to the
      tropics, one should consider both exotic and cosmopolite parasites. LABORATORY
      TESTS: The causal agent can sometimes be identified by direct examination of
      tissue samples, depending on the localization. In practice however identification
      may be a difficult task when the level of infestation is low or the helminth is
      in a larval stage. The epidemiological situation, clinical features and results
      of serology tests must all be considered for diagnosis. ANTIHELMINTH TREATMENT
      (TEST): Clinical improvement after treatment can be a criteria for positive
      diagnosis. Normal eosinophil counts followed later by normal serology confirms
      the diagnosis.

PMID- 9768008
TI  - [Hereditary neurological diseases caused by amplification of triplet
      repetitions].
AB  - NEW TYPE OF MUTATION: Repeated sequences of nucleotide triplets can cause two
      groups of diseases. GROUP I DISEASES: These diseases result from an expansion of
      a noncoding portion of a gene which may be repeated more than 1000 times. This
      group includes several multisystem diseases such as the fragile X syndrome and
      its variants, Steinert's disease and Friedreich's disease in which nervous system
      disorders are not always predominant. The molecular mechanism of the cellular
      disorder is probably related to a nonfunctional abnormal protein. GROUP II
      DISEASES: Huntington's disease, spinobulbar amyotrophy or Kennedy's disease,
      dentato-rubo-pallidolusian atrophy and spinocerebellar ataxias 1, 2, 3, 6, and 7
      are characterized by local expansion of the coding part of a gene. This low
      amplitude expansion always involves the CAG triplet and leads to expression of a
      protein with an abnormal number of glutamines, producing typical
      neurodegenerative disease almost exclusively limited to the nervous system. The
      underlying mechanism of the neuronal suffering is probably the production of an
      abnormal but functional protein. The causes of this type of mutation remain
      unclear. PERSPECTIVES: Positive diagnosis is now possible with DNA sequencing.
      While antenatal diagnosis offers essential information for family genetic
      counselling there is no perspective of therapeutic propositions for the near
      future. The problems raised by presymptomatic diagnosis must not be
      underestimated.

PMID- 9768009
TI  - [Lung cancer in patients infected with human immunodeficiency virus. Clinical
      course and therapeutic implications].
AB  - OBJECTIVES: HIV infection is associated with increased frequency of non-Hodgkin's
      lymphoma and Kaposi sarcoma. Like other malignancies, lung cancer has been
      described in HIV-infected patients although no evidence of a statistical
      correlation has been reported. PATIENTS AND METHODS: We performed a retrospective
      analysis of 15 HIV-infected patients with lung cancer. The patients were
      relatively younger (mean age 45 years) than is commonly found in lung cancer
      cohorts. RESULTS: The 15 patients had mild immunodepression (240 CD4+/mm3) and
      were in advanced clinical stage at diagnosis. Mean overall survival was 6 months
      and no clinical or biological prognostic factors were found. Death was usually
      due to infection, suggesting a synergetic effect between HIV and chemotherapy
      induced immunodepression. CONCLUSION: We propose early antiretroviral therapy in
      cases of chemotherapy-treated HIV patients, even when commonly accepted
      immunological and/or clinical criteria are absent.

PMID- 9768010
TI  - [Cholera in a Paris resident with no history of travel. A case report].
AB  - BACKGROUND: Cases of imported cholera are frequently observed, but cholera almost
      never occurs in subjects who have never travelled to an endemic area. In the last
      30 years, 4 cases have been reported. We report an indigenous case diagnosed in
      Paris in September 1996. CASE REPORT: The patient was hospitalized for severe
      dehydration and acute renal failure. Cultures of a fecal specimen grew Vibrio
      cholerae O1 Ogawa serotype. An epidemiological study was conducted to identify
      the vehicle and mode of contamination and suggested that this case was associated
      with the consumption of fresh sorrel imported from West Africa. No other cases
      were identified in contacts of the patient. DISCUSSION: Asymptomatic carriage of
      V. cholerae is rare. However, air travel has allowed people to arrive in non
      endemic areas during the incubation period. The agent may also be transported in
      contaminated foods. Cholera should be suspected in all adults presenting acute
      watery diarrhea with severe dehydration. History taking should also look for risk
      exposure and these patients should be systematically asked about possible
      exposures.

PMID- 9768011
TI  - [Pulmonary embolism of hydatic origin].
AB  - BACKGROUND: The right ventricle is an exceptional localization for hydatic cysts.
      There is a risk of hydatic embolism and chronic or acute cor pulmonale. CASE
      REPORT: A 63-year-old-man with an uneventful history was hospitalized for dry
      cough, exercise-induced dyspnea and bloody expectorations which had developed
      over the previous year. Multiple and bilateral opacities were visualized on the
      standard chest x-ray and the right border of the heart showed a bulge in the
      middle portion. Signs of right-sided hypertrophy were seen on the ECG. Imaging
      findings led to the diagnosis of multiple organ hydatiasis involving the lung,
      the liver the mediastinum and a ruptured hydatic cyst in the right ventricle. The
      cavogram revealed defect images in the superior vena cave and the pulmonary
      angiogram confirmed the diagnosis of hydatic embolism. Medical treatment was
      given but the patient died 8 months after diagnosis. DISCUSSION: Hydatic
      pulmonary embolism generally occurs after rupture of a hydatic cyst in the right
      ventricle or due to venous migration of daughter vesicles to the right heart then
      the pulmonary artery. Clinical manifestations are not specific although hemoptisy
      is the most frequent sign. Positive diagnosis, guided by echocardiographic
      findings, is based on the pulmonary arteriogram. Prognosis is particularly poor
      and depends of the patient's general status as well as the number and size of the
      embolized vessels. Survival rate is poor. Open heart surgery is indicated in
      localized forms.

PMID- 9768012
TI  - [Birth defect of the coronary arteries].

PMID- 9768013
TI  - [Late manifestation of GM1 gangliosidosis in an adult. An unusual case of
      multiple sclerosis].

PMID- 9768014
TI  - [Splenic hematoma during infectious mononucleosis: non-operative treatment].

PMID- 9768015
TI  - [Assessment of the placebo effect of symptomatic slow-acting anti-arthritics].
AB  - OBJECTIVES: Assess the importance of the mid-term placebo effect of symptomatic
      slow acting drugs given for osteoarthritis. METHODS: We analyzed six controlled
      trials available in the literature. Trial duration ranged from 2 to 6 months. The
      trials had been conducted to assess the symptomatic effect of diacerhein,
      avocado/soya unsaponifiable chondrontin sulfate and oxaceprolin given for
      osteoarthritis of the hip or knee. The main clinical outcomes assessed were
      functional impairment using the Lequesnes index and a visual analog scale.
      RESULTS: Globally, the trials showed decreased function impairment with a 2 to 3
      points decrease in the Lequesnes index (15 to 20%) and a 10 to 16 mm fall in the
      visual analog scale (-20 to -30%) in the placebo groups. CONCLUSION: Our findings
      confirms the importance of the mid-term placebo effect in the clinical course of
      osteoarthritis in patients given slow-acting drugs. This placebo effect, observed
      under these circumstances, is an expression of what clinicians will look for in
      future drugs and should be helpful for calculating the number of patients
      required in future trials.

PMID- 9768016
TI  - [Continuous intrathecal baclofen in a case of generalized tetanus].

PMID- 9768017
TI  - [Idiopathic calcium lithiasis. Dietary correction of metabolic risk factors.
      Physiopathological bases].

PMID- 9768018
TI  - [Idiopathic calcium lithiasis. Diuresis treatment].

PMID- 9768019
TI  - [Idiopathic calcium lithiasis. Practical guide for dietary measures
      prescriptions].

PMID- 9768020
TI  - [Echo Doppler classification of postoperative recurrence of varicose veins in the
      region of the internal saphenous vein].
AB  - OBJECTIVES: Surgical treatment of varicose veins of the lower limbs is frequently
      complicated by recurrence. Although recurrence was long thought to result from
      technical errors, certain patients have progressive disease. METHODS: We used
      duplex-Doppler to assess 102 patients (160 limbs) with recurrence after resection
      of the saphene-femoral junction with stripping of the internal saphenous vein and
      the varicose network on the medial aspect of the leg. A vein map was established
      to classify recurrences. RESULTS: Type I, junctional stump with incontinent
      collateral, was observed in 22.5% of the cases. Type II, sapheno-femoral junction
      in an anatomic position, was found in 18.1%. Type III, backward flow from a
      perforating vein or a collateral of the common femoral was found in 13.1% and
      type IV, cavemomous aspect, in 7.5%. In 45% of the cases, the patient had a
      progressive condition with backward flow from collateral branches in the perineal
      or inguinal area unconnected to the common femoral. DISCUSSION: The cause of
      recurrent varicose veins is a question of debate: inadequate or incomplete
      treatment versus disease progression. Due to the chronic and evolutive nature of
      varicose veins, duplex Doppler exploration is essential for the preoperative work
      up. Follow-up examinations should also be performed every year when the clinical
      examination suggests recurrence.

PMID- 9768021
TI  - [Improvement of prescriptions for serum tumor markers in a general hospital].
AB  - OBJECTIVES: Using a standardized prescription sheet we attempted to improve
      requests for serum tumor markers in a general hospital. METHODS: Over two 35-day
      periods before and one year after defining a local prescription consensus and
      introducing a new prescription sheet, we counted the number of orders for five
      tumor markers (CEA, CA 19-9, CA 15-3, CA 125, alpha FP) and determined their
      compliance to the defined prescription protocol. RESULTS: Between the two study
      periods, the number of prescriptions for the designated tumor markers fell by
      24%, from 153 requests in 94 patients to 123 requests in 99 patients, despite a
      6% increase in the number of admissions. There was a significant reduction in the
      number of serum markers orders per prescription (from 1.6 to 1.2) although the
      distribution by tumor marker remained unchanged. Compliance to the prescription
      protocol improved, rising from 65 to 87% in units where the pre-protocol
      compliance rate was below 80%. The rate of compliance was not correlated with
      correct completion of the new prescription sheet (91% vs 86% respectively). The 6
      month cost-savings was estimated at 31,104 FF using the general French
      nomenclature for laboratory tests. Direct cost reduction was estimated at 5,688
      FF. CONCLUSION: Long-lasting improvement of serum tumor marker prescriptions can
      be achieved in a general hospital. Obtaining a local consensus implicating all
      prescribing units seems more important than a change in the presentation of the
      prescription sheet.

PMID- 9768022
TI  - [Stromal tumors in the digestive tract. A case of duodenal localization].
AB  - BACKGROUND: Stromal tumors of the digestive tract are undifferentiated connective
      tissue tumors which are difficult to characterize even with immunohistochemistry.
      CASE REPORT: A stromal tumor of the duodenum (the most frequently encountered
      location) was resected entirely. Histochemistry was unable to provide a precise
      identification of the histological nature. The tumor was considered to be low
      grade due to the low mitosis index despite its large size and the presence of
      necrosis. Careful surveillance was indicated. DISCUSSION: The risk of these
      tumors is uncertain and may be assessed on the basis of histological prognosis
      factors such as tumor size, mitosis index and ploidy. Echoendoscopy can be
      particularly useful for diagnostic purposes providing information on location in
      the duodenal musculosa.

PMID- 9768023
TI  - [Splenic rupture revealing Waldenstrom disease].

PMID- 9768025
TI  - [Transient vascular accident, possibly related to intravenous immunoglobulins].

PMID- 9768024
TI  - [Acanthamoeba keratitis].

PMID- 9768026
TI  - [HIV seroconversion revealed by agranulocytosis].

PMID- 9768027
TI  - [Postpartum venous thrombosis. Differential diagnosis of postpartum anesthetic
      complications].

PMID- 9768028
TI  - [Trans-cervical collection of embryonic cells].

PMID- 9768029
TI  - [Acrosyndromes in AIDS].

PMID- 9768030
TI  - [Fracture of the sacrum caused by bone deficiency].

PMID- 9768031
TI  - [Compassion for pregnant women].

PMID- 9768032
TI  - [Quality and accreditation in health establishments. Application of experience
      acquired in the industrial setting].

PMID- 9768033
TI  - [Organ donation in France. Current situation and perspectives].
AB  - RECENT CRISIS: Strict legal regulations concerning human organ procurement in
      France emphasize the positive aspect of donation. While public opinion in France
      is generally favorable, organ donation passed through a crisis during the period
      between 1990 and 1994. The media played a crucial role. CONFIDENCE AND
      COORDINATED EFFORTS: The Etablissement francais des Greffes, in coordination with
      health care workers and non-governmental organizations, has developed a wide
      health education program aimed at gaining the confidence of the public and
      organizing hospital efforts to create an effective and serene procurement
      procedure. PERSPECTIVES: Procurement of cadaver organs remains essential despite
      the number of living-donors and ongoing development of artificial organs and
      xenografts.

PMID- 9768034
TI  - [Treatment of refractory spondylarthropathies].

PMID- 9768035
TI  - [Therapeutic management of cytomegalovirus infection in HIV-infected patients.
      Curative and pre-emptive treatment: results and uncertainties].

PMID- 9768036
TI  - [Kaposi disease].

PMID- 9768038
TI  - [Transesophageal echocardiography before electric cardioversion for
      supraventricular arrhythmia].
AB  - OBJECTIVES: The aim of this prospective study was to assess the risks of
      electrical shock cardio-version in the treatment of supraventricular rhythm
      disorders when administered under effective-dose but short duration
      anticoagulation in patients with no intracavitary thrombus detectable by
      transesophageal echocardiography. PATIENTS AND METHODS: One hundred nineteen
      patients, mean age 66 years, with permanent arrhythmia due to atrial fibrillation
      (n = 102), atrial flutter (n = 16) or atrial tachycardia (n = 1) and taking no
      long-term anticoagulant therapy were treated by electrical shock cardioversion.
      The patients were given heparin at an effective dose 72 hours prior to
      cardioversion. A transthoracic and a transesophageal echocardiography were
      performed less than 24 hours prior to cardioversion. RESULTS: Twenty-one thrombi
      were evidenced in 16 patients (14.6%) including 18 in the left auricle, 1 in the
      left atrium and 2 in the right atrium. A spontaneous contrast was visualized in
      38 patients (32%). Cardioversion was performed in 103 patients without thrombus
      and later in 9 of the 16 patients with thrombus after absorption under
      anticoagulant therapy as evidenced on the control transesophageal
      echocardiography. A sinus rhythm was obtained in 82% of the cases. All patients
      were given anti-vitamin K anticoagulants for one month. There were no clinical
      manifestation of ischemic vascular events during cardioversion nor during the one
      month follow-up. CONCLUSION: Early use of electrical shock cardioversion in
      patients with supraventricular rhythm disorders can be proposed without long-term
      anticoagulation therapy if the absence of thrombi is demonstrated by
      transesophageal echocardiography and short-term heparin is given followed by oral
      anticoagulants for at least 4 weeks. A large-scale randomized prospective study
      comparing the conventional strategy with the protocol used in this study would be
      required to definitively validate this approach and determine its possible
      advantages.

PMID- 9768037
TI  - [Prevention of venous thromboembolism. Survey of in-hospital medical practice].
AB  - OBJECTIVES: In an effort to improve the prevention of venous thromboembolism, the
      Nancy University Hospitals conducted a survey of medical practice concerning
      indications for preventive therapy and surveillance of platelet counts and anti
      Xa activity. METHODS: The survey involved 163 medical files. Questionnaires were
      filled out in 6 units (3 medical wards and 3 intensive care units). RESULTS:
      Indications for preventive therapy were found to be quite variable with the
      exception of very low risk of thromboembolism where the treat/do not treat ratio
      was 0.1/1, indicating a clear tendency for abstention. This ratio was 0.77/1 and
      0.38/1 respectively for low and moderate risk and 2/1 for high risk. There was
      undoubtedly a ward effect. The attitudes in practice tended toward non-prevention
      in patients without limited mobility. For platelet counts, an initial count was
      performed in 95% of the cases and during treatment in 38% although the specific
      rates were not the same for different types of units. Anti-Xa activity, which
      according to prevention recommendations need not to be determined, was not
      monitored in 88% of the cases. In accordance with prevention recommendations,
      anti-Xa activity was not determined in 88% of the cases. CONCLUSION: Further
      progress is needed in the prevention of venous thromboembolism and should be
      based on wider use of existing methods.

PMID- 9768039
TI  - [Group A Streptococcus pyomyositis].
AB  - BACKGROUND: Pyomyositis is a group of infectious diseases involving muscle
      tissue. Staphylococcus aureus is usually the causal agent. Group A Streptococcus
      infections are uncommonly isolated in pyomyositis. Streptococcal pyomyositis can
      be distinguished by its severity. Death rate may be as high as 50%. CASE REPORTS:
      Diagnosis of cervical pyomyositis was made in 2 patients on the basis of
      ultrasound and computerized tomography findings. Group A Streptococcus was
      isolated from local samples. The diagnosis was confirmed at surgery. Host defense
      mechanisms were not deficient in either patient. Outcome was favorable in both
      patients after antibiotic therapy. DISCUSSION: Because of the seventy of group A
      streptococcal pyomyositis, early diagnosis is essential for prognosis. Ultrasound
      and computerized tomography are very helpful. Group A streptococcal pyomyositis
      should be considered as a life-threatening disease.

PMID- 9768040
TI  - [Lung abscess caused by Pasteurella multocida, an unexpected germ...].

PMID- 9768041
TI  - [Cyst of the cruciate ligament of the knee. Treatment by simple radio-guided
      puncture].

PMID- 9768042
TI  - [Effect of corticotherapy on the course of a severe form of Nelson syndrome].

PMID- 9768043
TI  - [Treatment of malaria: let us be sensible!].

PMID- 9768044
TI  - [To everyone their own phantoms].

PMID- 9768045
TI  - [Drugs on the Internet. Hazards of public health].
AB  - The development of internet and more generally of telematics has given rise to
      many practical consequences in medicine. Whatever the context (communication,
      medias, teaching, imaging or data transmissions), Internet appears as a familiar
      tool in many medical fields. However some drift with harmful consequences for
      public health is emerging. This is particularly true for drugs sales via
      Internet. The absence of any control by health authorities over Internet drug
      sales raises acute legal problems for jurists, pharmacists, pharmacologists and
      public health physicians. A debate on the main difficulties is urgently needed.

PMID- 9768046
TI  - [Extracorporeal photochemotherapy: a new approach to immunosuppression in
      transplantation].

PMID- 9768047
TI  - [Current diagnostic procedure in aortic dissection].

PMID- 9768048
TI  - [Resection of hepatic metastases from colorectal cancer].

PMID- 9768049
TI  - [Tomodensitometric image of the lumbar spine. Study of 150 patients hospitalized
      for discal sciatica].
AB  - OBJECTIVES: There would be some discordance between patient expectations and
      expert recommendations concerning computed tomography (CT) of the spine for
      discal disorders. We analyzed patient opinion. PATIENTS AND METHODS: At
      admission, a 25-item questionnaire was given to 150 patients hospitalized in a
      rheumatology unit for discal sciatica. Patients were asked to express their
      expectations concerning the CT exploration. RESULTS: Seventy percent of the
      patients had already undergone CT explorations requested by a general
      practitioner (55%) or a specialist (45%), 20% had had two CT explorations and 20%
      magnetic resonance imaging. Seventy-five percent felt they should have had a CT
      scan earlier, 85% thought a CT should be performed for back pain of less than one
      month duration and 96% in case of sciatica for 2 months or more. Patients felt
      their exploration came "late" because the physician was under financial pressure
      (52%), had incorrectly appreciated the patient's need (28%) or was incompetent in
      the matter (22%). Nevertheless, 15% of the patients recognized that the CT scan
      could be useless and 89% knew that all cases of hernia are not operable. Thirty
      percent recognized that hernias can go undetected on the CT scan and 78% that
      they may remain asymptomatic. Finally, 56% of the patients thought that the CT
      scan would not change their treatment and only 23% expected to undergo surgery
      sooner because of the CT exploration. DISCUSSION: Several factors would explain
      what patients expect from CT exploration of the spine: patient understanding that
      causes other than discal hernia can cause back pain (98%) or sciatic (77%); their
      fear of having another disorder (56% wanted to be reassured, which would explain
      in part why 27% hoped the CT would improve pain, 50% wanted to "see" their discal
      hernia, and 30 wanted to eliminate another cause of their pain); patient distrust
      of clinical diagnosis which they felt was less pertinent than CT (80% of the
      patients for generalists and 70% for specialists). Patient expectations did not
      appear to be limited by fear of irradiation (unrecognized by 90% of the patients)
      nor the cost of the exploration which was overestimated by 70% of them.

PMID- 9768050
TI  - [Lead blood levels in children under 6 years of age in the Mans region].
AB  - OBJECTIVES: High lead levels in children can have a deleterious effect on
      intellectual development. We assessed blood lead levels in children in the Le
      Mans region. METHODS: Children aged between 6 months and 6 years were included in
      the study. Inclusion criteria were health status requiring a blood sample and
      amount of blood available after ordered tests sufficient for lead blood analysis.
      The study group included 365 children. RESULTS: Mean blood level in the 365
      children was 37.2 +/- 20.6 micrograms/l. Six of the children had blood levels
      greater than 100 mu/l. None of the children had a level over 200 micrograms/l.
      Location of the home or date of construction of the home were not significantly
      correlated to blood lead levels, however blood lead levels were higher in
      children with neurological or behavioral disorders. This observation was made in
      a limited number of children. CONCLUSION: The risk of excessively high blood lead
      levels in children under 6 years of age is low in the Le Mans region. There is
      however a risk when old houses are renovated or in children with neurological or
      behavior disorders.

PMID- 9768051
TI  - [Nephrotic syndrome revealing malignant thymoma].
AB  - BACKGROUND: A well-established manifestation of neoplastic disease, nephrotic
      syndrome is infrequently associated with thymoma. Only 18 cases have been
      reported in the literature. CASE REPORTS: A 65-year-old man and a 60-year-old
      woman were seen for nephrotic syndrome. Minimal change renal disease was observed
      in the first patient whose nephrotic syndrome was steroid resistant. The second
      patient had membranous glomerulopathy and pure red cell aplasia. In both cases,
      nephrotic syndrome revealed thymoma. DISCUSSION: The histological lesions in 17
      of the 18 biopsied cases reported in the literature were minimal change in 10,
      focal segmental glomerulonephritis in 4, proliferative glomerulonephritis in 2,
      and membranous glomerulopathy in only one. The outcome of the nephrotic syndrome
      was dependent on the success of the thymoma treatment. Some patients responded to
      steroid and immunosuppressive agents. Pure red cell aplasia is uncommon and
      prognosis is poor. It can be successfully treated with cyclosporin A as in our
      second case.

PMID- 9768053
TI  - [Thrombosis of the superior vena cava, hemolytic anemia and hyper
      homocysteinemia].

PMID- 9768052
TI  - [Interferon alpha and pamidronate: a useful combination in the treatment of
      osteoporosis and systemic mastocytosis].

PMID- 9768054
TI  - [Acute severe colitis induced by cytomegalovirus in an immunocompetent patient
      who underwent several blood transfusions].

PMID- 9768055
TI  - [Median HIV viral load and incidence of Cytomegalovirus viremia. Improvement in a
      cohort of HIV-infected patients followed-up between January 1996 and April 1007].

PMID- 9768056
TI  - [At the National Academy of Medicine. Presentation of the noxious effects of
      ultraviolet rays].

PMID- 9768057
TI  - [Failure of anti-pneumococcal vaccination in a splenectomized patient with HIV
      infection].

PMID- 9768059
TI  - [Arthrosis: a disease of the future].

PMID- 9768058
TI  - [Newly discovered role of glomerulonephritis mediators].

PMID- 9768060
TI  - [Physiopathology of arthrosis. The normal cartilage].

PMID- 9768061
TI  - [Physiopathogenesis of osteoarthritis. The arthritis cartilage].

PMID- 9768062
TI  - [Physiopathogenesis of arthrosis. Therapeutic perspectives].

PMID- 9768063
TI  - [Method of esthetic evaluation of the reconstructed breast after cancer. Report
      of 76 cases].
AB  - The authors propose a simple method of aesthetic evaluation of breast
      reconstructions after cancer, based on a 20-point score. In the 76 patients
      included in this study and mainly reconstructed by implant, the following seven
      criteria were evaluated by a score: the reconstructed breast, the symmetrized
      breast, symmetry of the 2 breasts, the areola, the nipple, the areolo-nipple
      complex (ANC) and the overall reconstruction. The first score was established
      during the visit by the patient and independently by the same plastic surgeon.
      The score was then established during two sessions of projection of standardized
      photographs, by two groups, A and B, composed of 9 nurses and secretaries and 10
      plastic surgeons, respectively. Statistical analysis of the results showed that
      the scores for these criteria were all correlated for all examiners. This study
      confirms the reliability of aesthetic evaluation of breast reconstruction after
      cancer, by a group composed of 2 men and 2 women, surgeons or non-surgeons, on
      photographs or on clinical examination, based on a 20-point score.

PMID- 9768064
TI  - [Prospective study of 100 cases of breast hypertrophy].
AB  - The authors performed a prospective study of 100 consecutive cases of mammary
      hypertrophy. Sixty were treated by McKissock's technique and forty by Thorek's
      technique. The patients were reviewed at the second and sixth postoperative
      months. A general study of the population was performed to specific their demand,
      which was functional in 90% of cases, and the various symptoms were quantified.
      74% of cases presented with psychological problems and a desire for aesthetic
      improvement was expressed by 67% of cases. Postoperatively, a functional
      improvement was obtained in 99% of cases, while psychological disorders resolved
      in 100% of cases. The satisfaction rate was very high: 79% of patients were very
      satisfied and 20% were satisfied. Some defects observed by the patients or
      surgical team are analysed. The complications observed, always minor, are
      reported. Breast reduction provides an unquestionable benefit for patients with
      mammary hypertrophy. Two simple and perfectly defined techniques were used to
      treat all these cases with a maximal satisfaction rate and a minimal complication
      rate.

PMID- 9768065
TI  - [Treatment of fibrous dysplasia of the cranio-facial bones. Report of 25 cases].
AB  - Fibrous dysplasia accounts for approximately 2% of bone tumors. The ribs,
      proximal femurs and cranio-facial bones represent the majority of bone lesions.
      Surgery is the mainstay of treatment but the technique is controversial:
      conservative surgery or removal of dysplastic lesions followed by implantation of
      autogenous bone graft. The aim of this study was to assess the indications of
      each method. The medical records of 25 patients with fibrous dysplasia of the
      cranio-facial bones treated between January 1, 1980 and December 31, 1994 at the
      Department of Maxillofacial Surgery, Centre Hospitalier Universitaire de
      Bordeaux, France, were reviewed. Fourteen (56%) patients were women and 11 (44%)
      men. The median age at the time of diagnosis was 23 years (ranging from 8 to 56
      years). The mean follow-up was 8 years. Two patients were unavailable for follow
      up after treatment. The primary sites of the tumors were the mandible (n = 19
      [76%]), maxilla (n = 1 [4%]) and skull (n = 5 [20%]). For mandibular lesions, the
      primary treatment always included a correction of deformations and asymmetry,
      which was the only treatment in 14 cases. Two patients required subsequent
      surgery to reduce further bone enlargement (1 and 2 years later in the first case
      and 11 years later in the second) without further problems. In 3 cases a
      segmental mandibulectomy followed by implantation of autogenous bone graft was
      required, and no further recurrence was observed. Therefore, the success rate of
      conservative surgery was 74% initially, and up to 86% after subsequent surgery.
      Skull lesions, although often very extensive, were remarkably stable and
      asymptomatic. They were successfully treated 4 times by conservative surgery,
      mainly for cosmetic reasons. One patient, with an ethmoidal tumor producing a
      mass effect along the course of the optic nerve, underwent a combined cranio
      facial resection. As for the only maxillary tumor, three curettages were
      performed throughout an 11-year period and there was no evidence of further
      recurrence 4 years after the last intervention. In all cases, conservative
      surgery may be recommended as primary treatment of fibrous of the craniofacial
      bones, providing essential structures like the optic nerve are not at risk.
      Cosmetic results and local control proved excellent, and a further removal of the
      tumor remained feasible in the event of a recurrence. Success or failure did not
      correlate with tumor size, which justifies the use of this technique.

PMID- 9768067
TI  - [Submental endotracheal intubation in craniomaxillofacial trauma. Technical
      note].
AB  - Submental intubation is a new technique of oroendotracheal intubation in patients
      with facial fracture requiring jaw control, associated with skull base fracture.
      First described by Altemir in 1986, the simplicity of this procedure and its
      minimal scar traces lead the authors to prefer it to tracheostomy in patients who
      do not need endotracheal intubation for more than 48 hours.

PMID- 9768066
TI  - [Secondary rhinoplasty for unilateral cleft lip and palate. Review of the
      literature and 50 clinical cases].
AB  - The nasal sequelae of unilateral cleft lip and palate are almost always present:
      more or less severe deformities, essentially consisting of nostril deformity and
      deviated septum. After an anatomical study of nasal deformities and the
      consequences of the primary procedures of cheiloplasty or cheilorhinoplasty, the
      authors review all of the most satisfactory technical aspects of secondary
      proposed in the literature. Five clinical cases illustrate the therapeutic
      strategy and the results.

PMID- 9768068
TI  - [Reconstruction of the mouth floor using a musculo-mucosal buccinator flap
      supplied by facial vessels. Report of ten cases].
AB  - The buccinator muscle is a wide, flat quadrangular muscle. Its medial surface is
      covered by the oral mucosa. It receives its arterial blood supply from two main
      arteries: the facial and buccal arteries. A musculo-mucosal flap can be raised on
      the facial artery with or without the facial vein. In the case of absence of the
      facial vein, venous drainage is possible into the peri-arterial loose areolar
      tissue. A nasolabial skin incision facilitates facial artery identification and
      simplifies flap dissection in the loose areolar plane, superficial to the facial
      artery. The mean dimensions of the flap are 3.5 cm in width and 7 cm in length.
      The flap extends from the superior buccal sulcus to the inferior alveolar ridge.
      Its rotation enables reconstruction of the anterior and lateral floor of the
      mouth. The donor site is closed in two layers. The authors present a series of
      ten patients reconstructed with this flap after excision of a squamous cell
      carcinoma of the floor of the mouth. The results are excellent with perfect
      tongue function and no esthetic sequelae. The facial artery should be preserved
      during neck dissection, and the ipsilateral mandibular molar teeth must be
      extracted. Its simplicity and reliability makes this flap a useful alternative in
      floor of mouth reconstruction.

PMID- 9768069
TI  - [Eponychial flap].
AB  - The author describes an original and new method to lengthen the fingernail plate
      in distal digital amputation. After digital amputation, the loss of substance
      concerns the pulp tissue and fingernail apparatus. Generally, most palmar falp
      techniques can restore functional and aesthetic pulp. The fingernail defect is
      obviously not tolerated by the patient and needs to be corrected. The eponychial
      flap is a backward cutaneous translation flap. This flap lengthens the nail plate
      and restores normal dimensions of the nail apparatus. Two clinical cases are
      reported. This technique should be reserved for reconstruction of stage I and II
      distal digital amputations.

PMID- 9768071
TI  - [Combined Latissimus dorsi and Serratus anterior reverse flow pedicle flap.
      Report of a clinical case].
AB  - The authors report a new local combined flap involving the distally based
      Latissimus dorsi muscle pedicled on the lumber perforating arteries and prolonged
      by the last three digitations of the Serratus anterior muscle supplied by the
      thoracic branch of the thoraco-dorsal artery. This artifice, never previously
      described, increased the bulk and arc of rotation of the dorsalis flap. It was
      thus possible to cover a wide defect on the posterior aspect of the sacro-iliac
      region in a patient previously operated for a highly malignant histiocytofibroma.
      The anatomic considerations, harvesting technique and advantages and drawbacks of
      this flap are discussed.

PMID- 9768070
TI  - ["Saphenous vascular loop" technique in the treatment of lower limb defects.
      Report of five cases].
AB  - Five patients with high energy trauma of the lower limb with tissue defect
      located in the knee or the proximal third of the leg underwent reconstruction
      with a free latissimus dorsi flap. This flap was connected to a vascular
      saphenous loop which initially creates an arterioveous shunt between proximal
      femoral vessels. This was performed in a single operation with two teams of
      surgeons. This technique was chosen because a healthy recipient pedicle was not
      available in the vicinity of the defect. Application of vein grafts is not the
      usual procedure but there are situations in which it becomes necessary. Our aim
      in this paper is to discuss these situations, to describe the technique used in
      our Hospital and to analyze the advantages and disadvantages of a one or two
      stage operation.

PMID- 9768072
TI  - [Aplasia of the skull without scalp anomalies. A case report].
AB  - The authors report an extremely rare case of cranio-facial anomaly, which, to our
      knowledge has previously been reported only once (1993, Chakraborty and al.).
      This male infant presented with a giant congenital bone defect of the skull in
      the vertex region (10 x 20 cm) with no scalp deficiency. Minimal turricephaly and
      moderate telorbitism were associated with minor limb anomalies, but psychometric
      assessment appeared normal. Non-surgical follow-up was initially decided, but
      spontaneous reossification was so moderate that skull reconstruction was decided
      at 28 months of age, because of traumatological risks. A full-size resin cephalic
      skeletal reconstruction was obtained by 3D computerized tomography utilizing
      stereolithography techniques. A titanium plate was customized on the resin model
      for ideal adaptation to the convex skull defect (8 x 16 cm). Surgery was simply
      performed, consisting of preliminary undermining between the dura mater and
      scalp, and screwing of the custom titanium plate. The initial follow-up was
      uneventful.

PMID- 9768073
TI  - [Rare local complication of breast augmentation].

PMID- 9768074
TI  - [L-shaped mammoplasty incision with a predefined plan. 80 cases].

PMID- 9768075
TI  - [Gunshot injuries and their reconstruction. What is new in 1998?].

PMID- 9768076
TI  - [The dynamics of projectile wounding. Concepts in ballistic injuries].
AB  - Analysis of the structure and terminal ballistic behavior of bullets provides a
      better understanding of their wounding power. The studies of ballistics
      specialists serve as a base. The concept of "scientific shot" remains an
      intellectual approach to a random phenomenon. Wound ballistic studies examine the
      behavior of projectiles in vivo or in a simulation medium. War events, in which
      projectiles do not meet requirements of international conventions, sport or
      hunting accidents, urban violence may confront the surgeon with various types of
      ballistic pathologies. The appropriate saying of Lindsey that the surgeons has to
      treat a wound and not a weapon should not justify etiologic ignorance.

PMID- 9768077
TI  - [Ballistic data for plastic surgeons].
AB  - After a brief review of portable firearms or small caliber guns, the authors
      discuss various concepts concerning wound ballistics. Kinetic energy plays an
      important part in the damaging action of bullets, while the concepts of "shock
      wave" and "stopping power" have been supereded by the definition of wound
      profiles. These profiles are characteristic of each bullet. Clinically, they take
      the form of a temporary cavitation zone and a permanent cavity. The reaction of
      tissues crossed by the bullet largely depend on the elasticity of these tissues
      and the presence of bone. The concept of high velocity bullets should be
      abandoned. The phenomenon of cavitation alone and its dramatic clinical
      consequences should be taken into account and must guide the therapeutic
      approach.

PMID- 9768078
TI  - [Gunshot injuries of the face. Clinical observations in 21 cases].
AB  - The authors report their experience of facial ballistic trauma based on a series
      of twenty one homogeneous cases. After a review of the aetiopathogenesis, the
      characteristics of facial shocks by missiles of fire arms are described, with
      particular emphasis on specific wounds encountered in the head and neck. Two
      classifications are suggested: on based on the main clinical features and the
      other based on the various types of bullets organized according to wound profiles
      and modern ballistics. This new ballistic classification is related to the
      clinical features. Although a better approach to ballistics and wound profiles
      helps to guide the clinical assessment, the medical and surgical treatments are
      based on same principles and approaches in war surgery and in civilian practice.

PMID- 9768079
TI  - [Gunshot injuries of the face. Analysis of 165 cases and reevaluation of the
      primary treatment].
AB  - Our large experience of shotgun injuries to the face emphasizes the need for a
      reappraisal of primary treatment for this poorly documented topic. The medical
      records of 165 patients, treated at our institution between january 1st, 1982 and
      december, 31st 1996 for such an injury, were reviewed. Almost all cases were
      exclusively self-inflicted lesions. The guns were mainly twelve-gauge and
      occasionally 16 or 20-gauge. Close range wounds in an heterogeneous area--soft
      tissue, mandible, muscles of the tongue and floor of the mouth, oral and nasal
      cavities, maxilla and paranasal sinuses--caused massive damage. A topographic
      classification based on the soft-tissue and bone loss is reported. After initial
      management (including securing the airway and control of bleeding), conservative
      debridement of all devitalized tissues and stabilization of the fractures were
      performed. As soon as possible, bone and soft tissue reconstruction was
      undertaken using local or distant flaps. However, immediate definitive
      reconstructive procedures were scarcely [corrected] used and only in particular
      cases. We believe that a carefully planned reconstruction schedule is required to
      achieve satisfactory appearance and function.

PMID- 9768080
TI  - [Mandibular reconstruction of gunshot wounds by progressive bone distraction.
      Report of five cases].
AB  - Five adult patients with gunshot wound defect underwent bilateral mandibular
      lengthening by an extraoral device. All patients presented with interrupting
      mandibular defect of 50 to 100 mm. Distraction of bone fragments led to
      mandibular reconstruction without bone grafting and simultaneous expansion of
      soft tissues, avoiding free or pedicled myocutaneous flaps for soft tissue
      reconstruction of the lower third of the face. Mandibular distraction also
      recreated the alveolar ridge with its attached mucosa which is equivalent to the
      gingiva. It can be used for dental rehabilitation by osseointegrated implants.
      Avoiding the morbidity and functional problems of classical flaps, mandibular
      distraction accelerates facial reconstruction, and social reinsertion of these
      patients.

PMID- 9768081
TI  - [Microsurgery and ballistic traumatology of the face].
AB  - The use of free flaps to fill and repair facial defects due to suicidal gunshot
      wounds has considerably extended and refined the possibilities available to
      reconstructive surgeon. The objective is no longer to close the defect at any
      cost, or "fill a hole", but to replace missing tissue by an identical tissue,
      able to restore an identical cosmetic appearance, support equivalent constraints,
      and restore analogous function. Retrospective analysis of 56 cases of large
      facial defects due to gunshot wounds revealed a total of 66 free flaps for 32
      cases. The vascular quality of the flaps allowed better integration in a
      sometimes hostile recipient site and markedly reduced the treatment time.
      Although the objective results obtained in the treatment of these severe defects
      remain poor, the first-line use of these multiple flaps, exclusively reserved for
      deep repair, as the basis for reconstruction, has modified our behaviour. A real
      medium-term treatment strategy, based on a decision flow-chart, can be proposed
      which, despite several inevitable failures, leaves less room for improvisation
      and piecemeal surgery. Free flaps are only the hidden part of the reconstruction,
      as surface cover uses local flaps and other conventional reconstructive surgery
      techniques. However, this humble, hidden role is nevertheless fundamental, in the
      strict sense of the term, and guides the general approach to this surgery.

PMID- 9768082
TI  - [Gunshot wounds of the extremities in civilian practice. Therapeutic approach in
      five cases with diaphyseal bone involvement].
AB  - The authors analyse 5 cases of gunshot wounds involving limbs with a diaphyseal
      fracture of the radius and ulna: 3 of the cases concern the radius and ulna and
      the remaining 2 involve the tibial bone. These wounds were encountered in
      civilian practice (3 rixes, 2 gun-shot injuries). In all of the cases, the
      emergency treatment consisted of extensive debridment, bone fixation by
      intramedullary nailing in most cases, cancellous iliac bone grafting in 2 cases,
      cover with a Latissimus dorsi free flap in 1 case. In all of the cases,
      development was free of infections bone union time was 3 to 12 months; last
      functional results were satisfactory.

PMID- 9768083
TI  - [The life of Maurice Virenque (1888-1946). From "Gueules Cassees" to
      cervicofacial facelift].
AB  - When going through the biography and bibliography of M. Virenque, one realizes
      that he was an outstanding maxillo-facial surgeon, who developed his knowledge
      mainly during the two world wars 1914-1918 and 1939-1945 and gave exceptional
      care to soldiers with severe face and skull injuries, the so-called "Gueules
      Cassees". Nevertheless, he did not disregard the importance of aesthetic surgery
      born between the two wars. Due to his large experience in maxillo-facial surgery
      and his broad knowledge of the anatomy of the face, he occupies a special place
      among the forerunners of facelifts by stressing on the importance of plication of
      the deep aponeurotic layers of the face, thus allowing the elaboration of a
      modified approach to the problems of the aging face.

PMID- 9768084
TI  - [Macroreimplantation of the upper limb. Results in 24 cases].
AB  - The authors present a retrospective study of 24 cases of macroreimplantations of
      the upper limb operated between 1985 and 1995. The upper limb survival rate was
      54%. The prognosis was better for sections distal to the middle third of the
      forearm. The cause of early failure was arterial thrombosis and that of later
      failures was muscle necrosis, responsible for infections and venous thromboses.
      The functional results are analysed as a function of the type of amputation.
      Sections outside of muscle zones or with nervous continuity have a more
      favourable prognosis. 33% of reimplantations obtained a good or excellent result
      according to Chen's criteria. Poor functional results are nevertheless associated
      with a number of positive points: protection sensitivity, useful elbow,
      psychological satisfaction of limb preservation.

PMID- 9768085
TI  - [Role of emergency reconstruction of fingers by the "reposition-flap" technique.
      Report of eight cases].
AB  - Following replantation failure, fingertip reconstruction was performed as an
      emergency "reposition-flap" procedure in seven patients (eight fingers). This
      technique was intended for amputations distal to the DIP joint in long fingers,
      and IP joint in the thumb. Pulp was excised on the amputated segment, and the
      remaining bone and nail bed were reattached to the proximal stump with Kirschner
      wires. Pulp was reconstructed with a local advancement and sensitive flap.
      Trophicity and nail regrowth as well as mobility and strength were satisfactory
      in five cases. MRI examination showed revascularization of the distal bone
      fragment in four cases. This procedure is an alternative to amputation after
      replantation failure when patients do not accept finger shortening. The more
      distal the amputation, the better is the result.

PMID- 9768086
TI  - [Posterior thoracic reconstruction with latissimus dorsi flap after partial
      amputation of the latissimus dorsi muscle for sarcoma of the back. Report of four
      cases].
AB  - Malignant fibrous histiocytomas (MFH) arising from the subcutaneous tissues of
      the posterior thoracic wall require wide, but usually non-transfixing, resection
      to ensure adequate resection margins, the only way to reduce the local recurrent
      rate. Due to its size and position, the Latissimus dorsi muscle usually requires
      partial amputation. However, its vascular anatomy allows it to be used as a
      musculocutaneous flap of the residual muscle to fill the defects created. Four
      clinical cases are reported. This technique reduces the complication rate and
      simplifies the postoperative course.

PMID- 9768087
TI  - [Under the epidermis, the dermis, or how to interpret skin cultures?].
AB  - After a brief review of the three basic principles of reconstruction of the skin
      (structure, antigenicity and function), the author presents the various skin
      culture techniques, tissue by tissue. He explains the main methods of
      reconstruction of natural or artificial dermal tissue and epidermal structures,
      and finally the in vitro simultaneous reconstruction of both tissues, dermis and
      epidermis; only this last technique can really be called "skin culture".

PMID- 9768088
TI  - [Intraluminal absorbable device to assist in vascular microanastomosis.
      Experimental study on 20 rat aortas].
AB  - The subject of this experimental study is a cylindrical device, with a gauge
      adjusted to the vessel lumen, which disintegrates in a few minutes. The goal of
      this device is to increase the reliability of vascular microanastomosis. This
      study was designed to assess the efficacy and drawbacks of the device. The device
      is a cylindrical sugar stick, 5 mm long and with a gauge of 1 mm. Ten Wistar rats
      underwent a standard end-to-end aortic anastomosis with interrupted sutures and
      ten underwent the same anastomosis with the device placed in the lumen of the
      proximal and distal vessel. The same surgeon performed all anastomoses. Clamp
      application time was recorded and anastomotic patency was tested in each case;
      the vessels were also examined histologically. The clamp application time was
      significantly lower (p < 0.01), and the patency rate significantly higher (p <
      0.01) in the group in which the device was used. There was no histologic sign of
      intima injury in either group. This very simple device facilitates
      microanastomosis. It reduces the ischemia time and increases the reliability of
      the anastomosis, avoiding transfixing sutures. These results suggest that
      clinical trials are warranted.

PMID- 9768089
TI  - [Vascular microanastomosis by eversion and stapling using VCS forceps.
      Presentation of the technique and experimental evaluation of its reliability].
AB  - With the objective of further improving the reliability of microvascular
      anastomoses, several different procedures are now available to microsurgeons,
      including eversion-stapling by VCS forceps. The authors start by presenting the
      technique, emphasizing the need for specific instruments and compliance with
      certain principles determining the success of these anastomoses. In the context
      of an experimental protocol in the pig, on vessels measuring an average of 2.5 mm
      in diameter, 80 anastomoses were performed by VCS stapling-eversion and studied
      clinically, histologically and ultrastructurally, comparing the results to those
      of conventional anastomoses by approximation-suture with needle and suture. In
      light of the results, eversion-stapling anastomoses appear to be more reliable
      due to the absence of intraluminal foreign body, permanent endothelial continuity
      and effective re-endothelialisation before day 7.

PMID- 9768090
TI  - [VCS microclip anastomosis on blood vessels of less than 2 millimeters in
      diameter. Preliminary experimental study in the rat].
AB  - The aim of this work was to study the possibilities and limits of the vascular
      microanastomoses with VCS microclips. VCS Microclips are a new mechanical
      anastomotic device, allowing a single operator to perform anastomoses without
      microsutures. The two arcuate limbs of the titanium microclips do not penetrate
      the vascular intima. The microclip anastomosis technique is based on symmetric
      eversion of the vessel walls, facilitated by everting forceps. We studied the
      medium and small Autosuture VCS microclips on different vessels ranging from 0.3
      to 2 millimeters in diameter: aorta, carotid artery, femoral artery and femoral
      vein. Thirty nine end-to-end or end-to-side anastomoses were performed on Wistar
      rats. These anastomoses were performed by a single operator without the use of
      sutures. Patency was studied by the "empty and refill" test immediately and at
      two months. Histologic analysis of the anastomosis was performed at two months
      (hematein-eosin and orcein stains on longitudinal sections). Four out of thirty
      nine anastomoses were occluded during the 15 minutes following clamp release.
      Failure was always due to a technical error and occurred during the first trials.
      The thirty five other anastomoses were patent immediately and at two months post
      operatively, except for the by-pass which was not viable. These anastomoses were
      still patent 30 minutes post-operatively. Light microscopy analysis confirmed
      that the microclip extremities did not penetrate the lumen, although the internal
      media was usually very thin at the level of the microclip jaws, especially for
      the smallest vessels. For vessels larger than 1 mm in diameter, the microclip
      extremities were usually outside the internal elastic lamina. No anastomotic
      aneurysm was found. Vascular healing was comparable with microsutures at 2
      months. Microvascular anastomoses performed with microclips have numerous
      advantages, compared to usual microsutures: they are two to three times quicker,
      they can be performed step by step without turning the clamp and they can be
      performed with the right or left hand. There is theoretically no thrombogenic
      risk. The drawbacks are the need for complementary training and the cost of
      microclips which is five to six times that of sutures. End-to-side anastomoses of
      small vessels are more difficult than end-to-end anastomoses. The recipient
      vessels must be larger than 1.5 mm in diameter, otherwise the anastomosis may
      become stenosed. Microclips are especially useful to save time, i.e. for multiple
      anastomoses and for anastomoses of vessels larger than 1 millimeter in diameter.
      Some modifications of the material could allow vascular or hollow organ
      anastomoses with endoscopic assistance.

PMID- 9768092
TI  - [Skin problems in severe retraction stiffness of the hand and fingers. Role of
      the so called "castle" flap].
AB  - Skin retraction is a commonly observed complication of severe joint stiffness in
      the hand. After freeing the joint, this raises the problem of closing the skin
      without tension to avoid necrosis, disunion or pain during early rehabilitation
      and splinting. We have used a simple rotation flap for PIP extension (and
      hyperextension) stiffness and a "castle" flap for PIP flexion retraction and for
      both extension and flexion stiffness of the MPJ. It consists in withdrawing the
      skin (dorsal or palmar) of the phalanx distal to the freed joint. We have used
      this flap in 13 clinical cases of severe stiffness and it allowed wide access to
      all structures involved and facilitated early post-operative mobilization.

PMID- 9768091
TI  - [Bone substitute with growth factor. Preliminary clinical cases for cranio- and
      maxillo-facial indications].
AB  - Several biological materials have been analyzed in combination with osteo
      inductive growths factors to determine whether such a system can replace bone
      grafting in surgical practice. Efforts have been aimed at the discovery of the
      best carriers and delivery systems. We present the results of the surgical
      treatment of 11 cranio-maxillo-facial defects in 9 patients using a combination
      of natural coral skeleton (NCS in blocks or granules), human fibrin glue and
      transforming growth factor beta-1 (TGF-beta 1) as a composite bone substitute.
      Three patients were initially excluded because of early extrusion of the
      materials due to a technical error. Clinical and radiological evaluation was
      performed in all cases, with the patient acting as his own control. Clinical
      firmness and radiological mineralization occurred in three quarters of cases. New
      bone formation was confirmed histologically in two of these patients. Clinically
      the initial results remained stable over a three years follow-up with staged
      surgical procedures performed on a number of patients. None of the patients
      suffered any detrimental effect from implantation of the bone substitute.
      Although the numbers in these series are limited, the association of TGF-beta 1,
      human fibrin glue and NCS represented an interesting step, although the clinical
      results could be improved. Important factors in the success of this technique
      appeared to be stabilisation of the biological materials, quality and asepsis of
      the surrounding tissue and the dose of growth factor.

PMID- 9768093
TI  - [Use of gracilis musculocutaneous flap in tissue loss caused by Fournier's
      gangrene. Apropos of 4 cases].
AB  - The gracilis myo-cutaneous flap was used in 4 patients to cover soft tissue
      defects of the perineal, scrotal, penile and inguinal regions after Fournier's
      gangrene. This is a simple technique, which allows a simultaneous reconstruction
      of the perineoscrotal region. Very satisfactory esthetic and functional results
      were obtained in the recipient and donor sites.

PMID- 9768094
TI  - [Abdominoplasty with dissociated intraparietal liposuction. Technical note].
AB  - Liposuction has greatly contributed to the improvement of the aesthetic result of
      abdominoplasties. However, one should consider the high rate of seroma when
      liposuction is performed via an inferior approach during abdominoplasty. The
      authors present a new approach to achieve complete liposuction of the abdominal
      wall during conventional abdominoplasty. This approach is carried out via
      submammary incision after previous undermining of the abdominal wall. A permanent
      assessment of the thickness of the wall allows the liposuction to stay strictly
      in fat tissue. Finally, there is a total independence between liposuction and the
      undermining procedure which allows minimization of the postoperative seroma. This
      technic seems particularly useful in a context of extensive abdominal adipose
      with flaccidity of the abdominal wall, requiring extensive undermining. Thanks to
      this procedure, the authors have performed a one-stage operation in many cases in
      which two operations would necessary previously have been.

PMID- 9768095
TI  - [Mammaplasty with an L-shaped scar and a pre-established design. Apropos of 80
      cases].
AB  - Over recent years, surgeons have tried to reduce the reduction mammaplasty scar.
      In this context, we use a surgical technique described by J.P. Chavoin,
      privileging "the remaining breast". Three advantages of this surgical method are
      derived from its technical choices: a superior dermal pedicle for preservation of
      the areolar nipple complex, preoperative drawing and finally a short incision
      with an inverted L scar. A retrospective study of 80 patients with 27 months of
      follow-up defines the advantages and disadvantages of this technique. Discomfort,
      indications, quality of results are evaluated with charts. Preoperative drawing
      and technique are described. This study shows this to be a reliable technique
      with good and constant results. Lastly, its indication is described in comparison
      with other techniques designed to achieve. Its preferential indication is
      moderately severe hypertrophy (500 g), which represents the majority of patients
      consulting us, but it can also be used in severe hypertrophy or even
      gigantomastia. Reduction of asymmetry also constitutes a good indication,
      facilitated by rigorous skin drawing based on precise anatomical landmarks. In
      addition to its broad indications, its advantages are marked vascular safety,
      rapid execution, constant results, while preserving the median part of the thorax
      from any scars.

PMID- 9768096
TI  - [Lipoid proteinosis: importance of dermabrasion. Apropos of a case].
AB  - The authors report case of lipoid proteinosis. This is an autosomal recessive
      genetic disease involving the skin and mucous membranes. Skin lesions have a
      granular appearance, with infiltration and wrinkling of the skin, especially on
      the face. The authors show the success of dermabrasion on skin lesions on the
      face of a 21-year-old girl displaying typical symptoms of lipoid proteinosis.

PMID- 9768098
TI  - [Voyage to Catalonia].

PMID- 9768097
TI  - [What is the cost of excision-suture of a skin lesion under local anesthesia? 2
      month prospective evaluation in a public sector hospital].
AB  - The purpose of this study was to assess the cost of a minimal surgical operation:
      skin surgery under local anesthesia in the outpatients department. A two-month
      prospective study was carried out on 149 operations, with a mean duration of 33
      minutes. The mean cost of the operation was 434 FF. Although this study is very
      specific and its results cannot be generalized, it gives a method and an order of
      magnitude. It shows that it is difficult to save money without decreasing the
      quality of the operation. The price list of the French national health care
      system, and the price of the surgeon himself are discussed.

PMID- 9768099
TI  - [Update mid-term review of the pedicular extension in reverse YV flow. Review of
      a 7-year experience].
AB  - Since 1990, the authors use a surgical procedure called reverse flow YV pedicle
      extension to transfer a flap distally to its donor site. Their clinical
      experience, based on of 8 different applications and more than 80 clinical cases,
      demonstrates the reliability of the procedure. Nevertheless, the latissimus dorsi
      transfer, based on scapular vessels, must be an exceptional indication due to the
      need to achieve a venous microanastomosis. Moreover, the "extreme lateral arm
      flap" is considered to require a precise preoperative anatomical assessment
      because of the variants of the pedicle bifurcation. The authors are convinced
      that further applications will extend their experience of this procedure.

PMID- 9768100
TI  - [The use of pedicular flap from the squared pronator muscle in the prevention and
      treatment of neuritis. Report of 8 cases].
AB  - The distal third of the forearm is a tendinous area, in which nerves could be
      irritated by surrounding skin scars or synovitis. In this area, a distally or
      proximally based pronator quadratus muscle flap could be used to wrap around the
      median or superficial branch of the radial nerve. Such flaps have been used
      successfully in eight cases, four cases of chronic neuritis, 2 cases of wrapping
      a median nerve graft and 2 cases of nerve coverage following trauma. All patients
      obtained pain relief with no alteration of finger movements.

PMID- 9768101
TI  - [Treatment of the sequelae of enucleation by septal chondro-mucosal composite
      graft. Report of 21 cases].
AB  - Enucleation frequently and progressively causes an enophtalmus and atrophia of
      the inferior eyelid, thereby leading to a height deficiency. Buccal mucous grafts
      give rise to phenomena such as secondary retraction. This may have complex and
      painful post-operative outcomes. However, when a septal chondromucous graft is
      performed, the height in the inferior palpebral part becomes more aesthetic, more
      retentive and quickly allows the wearing of a more voluminous prosthesis. Thus,
      the notinable enophtalmus can be corrected and the aesthetic quality of the
      looking is substantially restored. The authors report this surgical procedure and
      the results obtained with 21 patients which appear to be particularly promising.

PMID- 9768102
TI  - [Fasciitis following face lift].
AB  - Facial fasciitis or non infectious facial retractions are rare and surprising
      events after a facelift performed at any age. The signs are firm retraction
      located on one or both sides of the face or neck. They differ from salivary
      fistula, localised oedema, and limited hematoma, which may be the initial factor
      responsible for this curious outcome. We found a particular psychological status
      in these patients, who are often fragile and depressed and who obtain a secondary
      gain from this impaired status. The treatment of facial retraction (facial
      fasciitis is non surgical: we recommend local massage, patience and psychological
      help for quite a long time (6 months-one year). The outcome is spontaneously
      favorable, unless the patient automanipulates. A psychosomatic link must be
      considered. This transient facial retraction may correspond to some forms of hand
      retraction (such as Dupuytren's disease with spontaneous healing) or some
      thoracic retractions after insertion of mammary prosthesis. Facial fasciitis is a
      rare complication in our practice (1.4% of all patients) but must be recognized.

PMID- 9768103
TI  - [Effect of irradiation fields on the results of breast reconstruction with skin
      expansion after radiotherapy].
AB  - Deferred prosthetic breast reconstruction after skin expansion is considered to
      be difficult after radiotherapy. The authors report a series of 14 cases of
      reconstruction after radiotherapy, compared with 6 cases of reconstruction
      without radiotherapy. They reported a similar quality of results after
      radiotherapy not including irradiation of the chest wall and in the absence of
      radiotherapy (p = 0.742). On the other hand, a significant deterioration of the
      results was observed when radiotherapy included chest wall irradiation (p =
      0.0015). Finally, no direct correlation was observed between the macroscopic
      appearance of the skin and presence or absence of a history of irradiation of the
      chest wall. They conclude that the indications for reconstruction by tissue
      expansion after radiotherapy must be based more on the irradiation protocol than
      on the macroscopic appearance of the skin.

PMID- 9768104
TI  - [Surgical treatment of pterygium colli. A case report and review of the
      literature].
AB  - The authors describe the characteristics of the pterygium colli, symptom of
      several congenital diseases. Based on a review of the literature, they report the
      surgical techniques available to correct this deformity. This malformation may be
      due to asymmetrical development, inducing a vertical skin defect, which requires
      correction. The so-called posterior techniques are recommended; they allow good
      morphologic improvement (restoration of neck outline and natural posterior
      hairline), with minimal scarring. One case treated by a posterior technique is
      reported. Laterocervical skin expansion has been used by some authors, and seems
      to allow correction of these cutaneous anomalies, with a better morphologic and
      cosmetic result.

PMID- 9768105
TI  - [The use of the internal tissue expansion procedure in reconstructive surgery.
      Preliminary study and report of 2 cases].
AB  - The Frechet extender, initially proposed and successfully used in scalp
      reductions, can have many other indications in reconstructive surgery. This paper
      describes the preliminary results obtained after using this internal tissue
      extender in the treatment of a limb burn scar and a congenital giant naevus of
      the back. After a 3 month follow-up, these results are excellent. This procedure
      gives good results especially when there is a bony support underneath the skin to
      be treated.

PMID- 9768106
TI  - [Free fibula transplant and practical approach in the absence of posterior tibial
      artery. A report of 2 cases].
AB  - The authors report two well documented cases of absent posterior tibial artery in
      patients undergoing free fibula transplant. The first patient was a 50-year-old
      woman treated by pelvimandibulectomy for squamous cell carcinoma, leaving a
      defect of the floor of the mouth. The second case was an 11-year-old child with
      Ewing sarcoma of the femoral metaphysis, in whom femoral reconstruction was
      performed by vascularized free fibula transplant. Based on these two cases, the
      authors describe their diagnostic and therapeutic approach designed to avoid
      risks associated with this anatomical variant. Absence of the posterior tibial
      artery can be confirmed by arteriography and duplex ultrasound. The authors
      propose duplex ultrasound as first-line investigation as this safe, noninvasive
      examination provides sufficient information in the majority of cases at a lower
      cost. In parallel, the various anatomical variants affecting the origin of leg
      arteries from the popliteal artery are classified into seven groups based on a
      phylogenetic and embryological study.

PMID- 9768107
TI  - [Syringomatous tumor of the nipple. A case report and review of the literature].
AB  - The authors report a case of syringomatous tumor of the nipple in a 35-year-old
      woman, discovered incidentally during investigation of dysmenorrhea. After
      limited resection-biopsy of a cystic nipple tumor, histological results indicated
      the need for a partial central mastectomy with areola and nipple amputation.
      Although this tumor is classified as an adenoma, considered to be a benign
      lesion, syringomatous adenoma of the nipple is a potentially locally aggressive
      tumor, at risk of local recurrence and deep invasion of the mammary gland. This
      is a rare tumor (only 18 cases have been reported in the literature), and the
      histological diagnosis can be difficult, with possible confusion with a nipple
      duct adenoma, or tubular carcinoma.

PMID- 9768110
TI  - [Photography and plastic surgery. From scientific honesty in general...to
      photographic touching up in particular].

PMID- 9768108
TI  - [Erosive adenomatosis of the nipple. Report of 2 cases].
AB  - Superficial papillary adenomatosis of the nipple is a benign tumor of the ductal
      epithelium that clinically resembles Paget's disease. Unilateral serous, bloody,
      or serosanguinous discharge with crusting is most commonly present. Symptoms
      include tenderness or pruritus. Histologically, the tumor is characterized by
      proliferating ductal structures lined by a double layer of columnar epithelium.
      The lesions are focally eroded. Keratin cysts and apical intraluminal projections
      are commonly found. The original description was reported in 1954 in the english
      language literature. Just a few cases have been reported in the french
      literature. These cases are reviewed and two classic examples are reported; their
      therapeutic options are discussed.

PMID- 9768111
TI  - [Genetics of craniofacial malformations].
AB  - The most frequent craniofaciosynostoses, Crouzon, Apert and Pfeiffer syndromes,
      are due to mutations of genes coding for FGF growth factor receptors (FGFR). The
      Twist gene has been recently implicated in Saethre-Chotzen syndrome. The current
      confusion concerning phenotypegenotype correlation is starting to be clarified by
      the increasing number of cases in which the mutations have been identified and
      the clinical classification will need to be revised in the light of the results
      of molecular genetics.

PMID- 9768112
TI  - [Modern imaging of craniofacial malformations].
AB  - Due to progress in the field of medical imaging of craniofacial malformations,
      the place of these investigations in the assessment of these abnormalities needs
      to be revised. 3D CT scan currently remains the fundamental element of the
      assessment by providing a truly anatomical dissection of each bone. In the field
      of craniostenoses, the study of the base of the skull has allowed a new
      assessment of lesions of skull base and craniofacial sutures and the resulting
      skeletal deformities: they provide restrospective justification for an extensive
      approach to the surgery of this group of malformations and a basis for reflection
      concerning extension to direct skull base surgery. Craniofacial clefts constitute
      a heterogeneous groupe of anomalies in which Tessier's concepts have allowed a
      methodical approach. 3D CT allows better definition of certain subgroups of
      malformations within this group (midfacial clefts) and provides a clearer
      understanding of the skeletal defects of maxillary clefts, especially in the
      laterofacial region. This imaging is currently undergoing rapid development.
      Improvement of 3D CT scanning techniques (direct 3D image acquisition,
      improvement of the images obtained), development and combination of 3D MRI, after
      being superimposed onto the skeletal image, will allow total dissection of the
      malformation. Development of 3D cephalometric analysis techniques and growth
      analysis software will allow really predictive "image-assisted surgery". Finally,
      antenatal imaging (B-mode and 3D ultrasonography) makes a considerable
      contribution to this field of anomalies by allowing the diagnosis of serious or
      severely disabling anomalies and by elucidating the antenatal development of
      certain anomalies (especially craniostenoses) and their consequences.

PMID- 9768113
TI  - [Unusual facial clefts].
AB  - After briefly review facial morphogenesis, the authors define facial clefts,
      distinguishing primary clefts, secondary clefts, and residual clefts. They
      discuss the uncertainties surrounding the embryology and clinical features of
      palpebral colobomas. The various pathogenetic concepts are analysed: amniotic
      hypothesis, vascular hypothesis, fusion defect. The various classifications of
      rare facial clefts are reviewed, with particular emphasis on Tessier's
      classification and the so-called Milan classification. The general principles of
      surgical treatment are described together with the various skeletal and soft
      tissues procedures.

PMID- 9768114
TI  - [Craniosynostosis and faciocraniosynostosis].
AB  - The authors present a review of the aetiopathogenesis and treatment, based on a
      series of 1321 craniostenoses operated by the Enfants Malades team. After briefly
      reviewing the embryology of craniofacial growth, the authors describe the
      morphological classification of craniostenoses and their morphological and
      functional consequences. The main neurosurgical problems related to craniofacial
      surgery are described. The surgical techniques currently used by the unit are
      described for each type of craniostenosis, according to age: H or flap
      transposition craniectomies for scaphocephaly, unilateral advancement of a
      bilateral head-band for plagiocephaly, anterior transposition for oxycephaly, and
      fronto-orbital adbancement for brachycephaly. The results are presented with a
      follow-up of several years. The principles of one-stage or two-stage surgical
      treatment for the main types of faciocraniostenosis are recalled: initial fronto
      orbital advancement then secondary treatment of maxillary recession. The
      prospects of one-stage combined treatment with early maxillary distraction are
      proposed. Surgical indications are described. The complications, morbidity and
      mortality are indicated for the series. It must be remembered that craniostenosis
      surgery is a form of plastic surgery with neurosurgical complications. To obtain
      optimal results with the lowest risk, craniofacial must be performed by
      multidisciplinary teams in specialized centres.

PMID- 9768115
TI  - [Maxillo-mandibular ++disharmonies].
AB  - The maxilla and mandible give the face its proportions and equilibrium, while
      remaining indissociable from the skull. The harmony of these structures is
      established according to two planes of reference: the base of the skull in a
      relationship of cranio-facial interdependence, the dental arch making the
      occlusal relationship a decisive factor in the concept of facial equilibrium.
      This occlusal obligation, criterion of normality and stability, confers all of
      the originality of orthognatic surgery, which must also take into account the
      periods of cranio-facial growth and oro-facial functions. The authors describe
      the modern concept of this surgery, the essential place of orthodontic
      preparation, and technical innovations such as computer-assisted simulation.

PMID- 9768116
TI  - [The posterior cranium and its dysmorphisms].
AB  - The deformation of the posterior part of the skull (occipito-vertebral region)
      induced directly, occurs in numerous pathological situations. Its significance is
      frequently overlooked. Lesions of the cranial content, alterations of the
      lambdoid suture or other premature synostosis, abnormal constraint related to
      posture or to muscular activity can modify the posterior curvature of the skull,
      generally flattening it. The authors propose a classification based on three
      points: intracranial pathology, bone pathology and extrinsic pathology.
      Concerning intracranial pathology, alterations of the brain or CSF fluid can
      induce either insufficient (microencephaly) or excessive (hydrocephalus, Dandy
      Walker or Arnold Chiari malformations) expansion. Concerning bone pathology,
      sagittal synostosis (scaphocephaly) induces a bulging and coronal synostosis a
      flatness of the posterior skull. Bilateral premature lambdoid synostosis
      (pachycephaly) produces total flatness of the back of the skull. Concerning
      extrinsic pathology, dysmorphism is often asymmetrical and results from
      extracranial mechanical application dysfunction such as inborn torticollis,
      cervical spine pathology (Klippel-Feil syndrome), or prolonged decubitus during
      the first year of life. The different surgical procedures are described and the
      authors describe a personal technique for correcting this dysmorphism: the turned
      biparietal flap transposition. The back of the skull is remodelled (either
      asymmetrical or bilateral flatness), and patients with no need for a helmet can
      lie on their backs immediately after the operation.

PMID- 9768117
TI  - [Surgical treatment of micro-ophthalmic syndromes].
AB  - The complex embryology of the oculo-orbito-palpebral region is responsible for a
      number of heterogeneous clinicopathological situations, associating variable
      proportions of the three components of the malformation: micro-anophthalmia,
      microblepharism, micro-orbitism. Application of the double principle of skin
      expansion for the eyelids and distraction of the callus for the orbit, as early
      as possible (first year of life), is possible by means of a device which consists
      of a combination of an intraorbital expansion balloon, an antireflux valve to
      avoid effective pressure losses in the balloon, and an injection site for
      progressive filling of the expansion balloon. The response to these treatments is
      excellent for cases of simple microphthalmia and micro-orbitism; in complex
      craniofacial malformations, it generally only partially resolves the problem, but
      provides a precious complement to the quality of the final repair.

PMID- 9768118
TI  - [Mandibular distraction].
AB  - The authors review the bone lengthening techniques used in orthopaedics, analyse
      the application of osteogenesis by surgical distraction of the mandible and
      describe the progress in techniques and equipment. The presentation of clinical
      cases of mandibular hypoplasia treated by intraoral distraction emphasizes the
      value of this new technique, particularly in terms of the morphological results,
      which are superior to those obtained by conventional techniques.

PMID- 9768119
TI  - [Distraction of the maxilla].
AB  - The distraction of the maxilla provides very useful possibilities in young
      children with unstable articulation and in infants in order to avoid excessively
      radical operations. The principles of the distraction are reviewed. The authors
      report 13 clinical cases and complications. The material needs to be perfected,
      as numerous incidents are still observed.

PMID- 9768120
TI  - [Contribution of microsurgical transfers in filling cranio-facial substantial
      losses].
AB  - In the series reported in the literature, microsurgical transfers for
      craniofacial reconstruction generally concern the face. The authors present a
      series of four complex reconstructions of the cranial vault and orbital floor. In
      one case, they used a prefabricated radial pedicle flap and, in the other cases,
      they used two-stage cover flaps, with satisfactory results.

PMID- 9768121
TI  - [The external carotid vein. Historical review of Paul Launay's work].
AB  - The authors, one century later, review the anatomical studies conducted by
      Launay, a student of Farabeuf, concerning the venous drainage of the face and
      neck. These studies were based on the analogy between the arterial system and the
      venous drainage of the external carotid territory. After describing the external
      carotid vein, the didactic and practical aspects of this study are emphasized.

PMID- 9768122
TI  - [Mental prognosis of trigonocephaly and therapeutic implications].
AB  - The authors assessed the long-term mental prognosis of trigonocephaly, in a
      series of 76 operated cases. Mental prognosis factors were studied, showing that
      early cranial release and reconstruction were effective. Final assessment of
      mental development was performed on children of school age, and was based on the
      development of behavioral disturbances, learning disability, school difficulties,
      and intellectual efficiency. Children were graded into 3 groups: no abnormality,
      mild abnormalities with normal socialization, major abnormalities; 31.6%
      presented disorders. Preoperative C-T scans assessed the severity of the cranial
      deformity and identified associated intracranial abnormalities, such as agenesis
      of the corpus callosum, dilatation of the subdural spaces, or hydrocephalus.
      Associated extracranial malformations, and associated family cases were also
      noted. Finally, the quality of the family context was studied. Several
      correlations were identified; mental development was correlated with the severity
      of frontal stenosis, the age at surgery and the associated extracranial
      malformations. Family environment also had a major influence. Intracranial
      abnormalities were not correlated with mental development.

PMID- 9768123
TI  - [Iatrogenic extravasations of cytotoxic or hyperosmolar aqueous solutions. Value
      of surgical emergency by aspiration and lavage].
AB  - Iatrogenic extravasations are characterized by their unpredictable course, the
      possible repercussions of functional, cosmetic and psychological sequelae, and
      the absence of a therapeutic consensus. The authors present the protocol used in
      Hopital Saint-Louis, based on a synthesis of current procedures, consisting of
      emergency conservative surgical aspiration and lavage, performed in a context of
      close collaboration with oncolosits, intensive care physicians and radiologists.
      From 1994 to March 1997, fifteen patients were operated following extravasation
      during seven chemotherapeutic protocols, three radiographic examinations with
      injection of contrast agents and five resuscitation procedures. This simple
      protocol, applied systematically, achieved cure without cutaneous or functional
      sequelae in all patients. Aspiration-lavage during the first twelve hours
      therefore constitutes the treatment of choice of iatrogenic extravasation with
      cytotoxic or hyperosmolar aqueous solutions.

PMID- 9768124
TI  - [Skin sensitivity before and after reduction mammaplasty. Report of 44 cases].
AB  - The main aim of reductive surgery for breast hypertrophy has often been the
      aesthetic result without considering on the cutaneous sensitivity. This
      retrospective analysis studied the subjective and objective sensitivity after
      mammoplasty reduction 44 patients. The preoperative results showed a reduction of
      sensitivity directly proportional to the ptosis. After surgery the patients
      described an improvement of the sensibility, especially in the case of moderate
      resection. This study shows the good restoration of nerve fibers after chronic
      stretching due to hypertrophy. Nerve fibres were restored when areolar graft was
      used.

PMID- 9768125
TI  - [Complex facial nevus in children treated by combination of prosthetic and
      deferred natural expansions].
AB  - Congenital pigmented naevi of the face in children represent indications for
      early excision and the search for the best aesthetic result has led the authors
      to prefer the use of skin expansion techniques. The case presented here
      illustrates the combined use of two expansion techniques: prosthetic expansion
      and natural differed expansion. This procedure gives good cosmetic results at a
      moderate overall cost.

PMID- 9768126
TI  - [Desmoplastic malignant melanoma of the ear. A case report].
AB  - A case of desmoplastic melanoma in a 72-year-old patient is reported. In the
      light of this case, the authors review the literature and analyse the therapeutic
      implications.

PMID- 9768127
TI  - [Lipoma of the superficial lobe of the parotid gland. A case report].
AB  - We report the case of a patient with a lipoma of the superficial lobe of the
      right parotid gland. Lipomas of the parotid gland are very rare. They are said to
      constitute one to two percent of all parotid tumours. Only six cases were found
      in the recent literature. Preoperative diagnosis is difficult when the physical
      examination reveals a renitent, well-localized and painless mass. However,
      magnetic resonance imaging is now the imaging modality of choice to facilitate
      the diagnosis, but the diagnosis can only be confirmed by histological
      examination of the tumour. We discuss the value of superficial parotidectomy,
      while some authors suggest an enucleation of lipomas of the superficial lobe of
      parotid.

PMID- 9768128
TI  - [Malignant melanoma in a 7-year-old child. A report of a dramatic case].
AB  - Malignant melanoma developed on the scalp at the site of a congenital nevus in a
      7-year-old girl. At birth, simple observation was proposed, despite the
      recognized desirable but non-urgent indication for excision, in order to avoid
      subjecting the infant to general anesthesia. At the first sign of a change in the
      macroscopic appearance of the nevus, surgical resection was performed, but the
      short-term outcome was fatal.... This case focuses our attention on malignant
      progression of even small congenital nevi and emphasizes the need for early
      preventive and systematic resection even when the patient's age of the patient
      requires general anesthesia.

PMID- 9768129
TI  - [Hemifacial atrophy. A case report associated with linear scleroderma].
AB  - The authors report a case of facial hemiatrophy, secondary to linear scleroderma,
      and review the various possible causes of facial hemiatrophy. The various
      treatments proposed to correct facial hemiatrophy are described. The advantages
      and disadvantages of each technique together with their indications as a function
      of the severity of the lesions are then discussed. Free flap currently appears to
      be the treatment of choice in severe forms and the main question concerns the
      choice of flap. The authors prefer an inverted dermal fat flap because of its
      advantages (absence of long-term ptosis, better facial contours) and the absence
      of laparotomy.

PMID- 9768130
TI  - [Conservative cervico-facial facelift. Concept and preliminary results].
AB  - A new cervico-facial facelift is presented, taking into account the cervico
      facial cutaneomusculo-aponeurotic unit (CMAU) comprising skin, subcutaneous
      adipose tissue, superficial musculo-aponeurotic system and the particular
      mechanism of cervico-facial ageing. The undermining, limited to the parotido
      masseretic region, is not subcutaneous, but immediately submusculoaponeurotic.
      The advantage of this facelift is to replace all of the CMAU over the underlying
      musculo-aponeurotic or osteo-periosteal planes, without modifying superficial
      relations. The cutaneous detachment preserves the natural appearance of the face
      and avoids the classical complications of facelift.

PMID- 9768131
TI  - [Indications and results of breast implant replacement with implants pre-filled
      with silicone gel].
AB  - Based on a series of 74 patients, the authors report their experience of
      reoperation on unsatisfactory breast implants by the implant replacement
      technique using silicone prefilled implants. In 92 (57.8%) of the 160 cases, the
      implant was modified because of a peri-implant capsule, with a satisfactory
      aesthetic result after only a single operation. However, this leaves the problem
      of repeated surgical operations, especially in the context of Baker stage IV
      capsules, which are only partially improved after two to three surgical
      operations. A particular surgical revision technique is required in the cases,
      while the role of in situ cortivazol is under investigation. This series
      comprises two patients with auto-immune disease and dysimmune profiles, not
      exarcerbate by secondary surgery. Analysis of this series clearly argues in
      favour of reoperation for unsatisfactory breasts implants. Squeezing manoeuvres
      appear to be dangerous and useless. Textured implants filled with very cohesive
      silicone gel should be maintened in view of the absence of any reported serious
      complications.

PMID- 9768132
TI  - [Paraffinomas: history, clinical features and treatment. A case report].
AB  - One case of paraffinoma is reported on a 60 years old man following injections of
      paraffin fourty years ago. The authors recalled with this observation history of
      paraffin, clinical aspect and surgical treatment of the paraffinoma.

PMID- 9768133
TI  - [Severe cutaneous necrosis after ultrasound lipolysis. Medicolegal aspects and
      review].
AB  - The authors report the case of a young patient who developed extensive skin
      necrosis after ultrasound liposuction of the medial surface of the thigh. These
      lesions required excision, split-skin graft and installation of an expansion
      prosthesis. The medicolegal aspects of this case are discussed, in particular the
      responsibility of the doctor who performed this damaging procedure, from three
      points of view: damage, fault, causality. In this case, the damage corresponded
      to necrosis which can be due to a chemical, infectious or thermal mechanism. It
      is responsible for serious damages due to the number of operations, the length of
      hospital stay, immobilization, rehabilitation and the time off work. The
      aesthetic damage, the pretium doloris, and the inconvenience are certainly
      considerable, but was there fault in this case? Fault by clumsiness if the
      equipment was used abnormally; fault by negligence or imprudence when the
      equipment was not approved or when the operator was not a qualified physician,
      submitting his patient to undue risks. The causality is envisaged in the case of
      chemonecrosis and burns. It would be strongly presumed in a civil procedure in
      case of non-approved equipment. The authors are in favour of a hypothesis of a
      burn and review the current state of ultrasound liposuction, which was the
      subject of an intense media campaign several years ago.

PMID- 9768134
TI  - [Hypoglossal-facial anastomosis. A report of 60 cases].
AB  - The authors report their experience of 60 cases of hypoglosso-facial anastomosis.
      The results of this retrospective series were analysed by the same examiner
      according to the House and Brackmann classification. The surgical technique is
      rapidly described, with emphasis on the important points. The results are
      analysed as a function of the interval between the anastomosis and facial
      paralysis: better and more rapid results are obtained when surgery is performed
      early (80% of grade 3 with immediate surgery versus 50% in very late surgery
      after more than 4 years). However, grade 3 or 4 can be obtained in every case,
      even in the case of very late surgery. Other favourable prognostic factors were
      revealed by this study: specialized rehabilitation and especially the patient's
      psychological must be integrated in this nerve transfer. In view of these good
      results and the limited adverse effects (atrophy of the hemi-tongue, eye-mouth
      synkinesias), hypoglosso-facial anastomosis must be part of the therapeutic
      strategy of total, permanent facial paralysis.

PMID- 9768135
TI  - [Lengthening of temporalis myoplasty and reanimation of lips. Technical notes].
AB  - The author reports a new myoplasty technique which separates the temporalis
      muscle from the temporal fossa and allows lengthening by redistribution of
      muscular fibers to the detriment of the posterior third. This allows the transfer
      of the coronoid tendinous insertions onto the lips. This technique preserves the
      two neurovascular supplies and does not distort the cheek. The indication
      purposed is lips reanimation.

PMID- 9768136
TI  - [Antley-Bixler syndrome. Description of two new cases and review of the
      literature. Prognostic and therapeutic aspects].
AB  - Antley-Bixler syndrome was first described in 1975, and to date, 20 cases have
      been reported. In addition to brachycephaly, the syndrome is associated with
      midface hypoplasia often with choanal stenosis or atresia, bilateral radiohumeral
      synostosis, multiple joint contractures, femoral bowing and long bone fractures,
      "pear-shaped nose", dysplasic ears, and occasionally urogenital or cardiac
      defects. Survival is closely linked to upper airway obstruction, which also
      affects (with craniosynostosis) mental prognosis. Association and severity of
      malformations are variable, and while numerous children have died early from
      respiratory distress, one third of them are alive, and have had quite
      satisfactory development. With early and effective prevention of respiratory
      complications, and early treatment of craniosynostosis, overall prognosis can be
      favorable. The mode of inheritance is probably autosomal recessive and
      midtrimester prenatal diagnosis is feasible; genetic counseling depends on
      accurate prognostic and therapeutic data. We describe 2 further cases. The first
      a 4 years old male, with unilateral coronal synostosis and radiohumeral
      synostosis predominating on the same side. The second an 18 months old female,
      with brachycephaly and an imperforate anus.

PMID- 9768137
TI  - [Plantar verrucous carcinoma. A case report and literature review].
AB  - The authors report a case of carcinoma cuniculatum plantar and review the
      literature on this rare tumour. The clinical features and course of this tumour.
      The clinical features and course of this tumour are successively described.
      Although associated with limited malignancy and almost exclusively local
      extension, progression of this disease may lead to amputation, which can be
      avoided by early diagnosis, especially based on precise histological examination
      of all tumours with a benign recurrent appearance after well conducted treatment.

PMID- 9768138
TI  - [Anatomo-clinical study of the inverted fascia-subcutaneous leg flap].
AB  - The authors report their experience in the use of the reversed fascio
      subcutaneous flap of the leg in 11 cases for covering soft tissue defects of the
      distal third of the leg, the malloli and the posterior heel. An anatomical study
      has been performed on fifteen fresh cadavers (30 legs), in order to precise the
      indications and limits in the dissection of the flap pedicle. The authors report
      six necrosis (2 superficial, 4 total) of the distal part of the flap. Despite
      these complications, they consider that this flap is an interesting procedure due
      to its advantages: the respect to anatomical structures, an easy dissection, a
      supple pedicle and an aesthetic aspect of the donor area.

PMID- 9768139
TI  - [Covering of a thoraco-lumbar defect by omentoplasty].
AB  - With a case of thoraco-lumbar defect, the authors discuss about different
      procedures to cover it. In this place, the better procedure is certainly the
      latissimus dorsi flap, in all combinations. The indication for omentoplasty at
      this spinal site should not be performed by first intention but by exclusion of
      other procedures, as in the case considered by the authors. It was a 37-year-old
      man, paraplegic from the age of 16, with a deep chronic spinal wound, secondary
      to sepsis of a posterior segmental fixations. A staphylococcus aureus infection
      which developed as a surgical complication was initially treated with antibiotics
      and surgical cleaning procedures without removing instrumentation. However, the
      infection remained active and the material was finally removed. Spinal
      immobilisation was strengthened by external fixation. The area was cleared of all
      suspect material, including bone graft, leaving a wide back-wound open to the
      spine. Spontaneous healing was first attempted, but the size and the chronicity
      of the wound led us to use pedicled greater omentum to close the defect. The
      omentum was pedicled on the right gastroepiploic vessels and transferred to the
      back wound through the posterior abdominal wall muscles, next to the right
      kidney. This procedure allows rapid healing. In association with suitable
      antibiotics, it has prevented any recurrent infection after 18 months of follow
      up. It was no feasible to cover the wound with a latissimus dorsi flap,
      considering the importance of this muscle in the movements of a paraplegic and
      considering the initial impossibility of removing the external fixation.

PMID- 9768140
TI  - [The history of cranioplasty].
AB  - Cranioplasties were first performed at the dawn of the history of medicine, as
      they usually constitute the repair phase of trephination. In preColumbian
      civilizations, they usually consisted of simple interposition of metal sheets
      under the scalp. Hippocrates and especially Galien prohibited this surgery and
      their principles were respected until the 18th century, although a remarkable
      surgeon, Van Meekeren, succeeded in performing a heterologous cranial bone graft
      from dog to man in 1668. The discovery of the osteogenic role of periosteum by
      Duhamel in 1742 opened the way to new research. During the 19th century, there
      was an extraordinary growth of science, during which all of the bases of the
      modern medical approach were established. For example, the studies by Ollier in
      1859 allowed the first cranial reconstructions by heterologous, homologous and
      autologous bone transfers. The large number of head injuries left by the First
      World War promoted the growth of bone cranioplasties, as shown by Delageniere.
      The discovery of antibiotics allowed the reintroduction of cranioplasties using
      inert materials such as acrylic resins. However, their excessive use was
      complicated by numerous cases of infectious rejection. At the end of the 20th
      century, microsurgery and molecular biology have provided solutions, but have
      still not resolved the dilemma between reconstructions by autologous or foreign
      materials.

PMID- 9768142
TI  - [On breast implants].

PMID- 9768143
TI  - [Breast reconstruction after mastectomy and breast implants. Current status in
      the USA].
AB  - The author review breast reconstruction after mastectomy for cancer, taking
      account the technical progress and problems raised by breast implants over the
      last twenty years. Immediate breast reconstruction has become a routine clinical
      practice. The principle, indications and complications of reconstruction
      techniques are presented: temporary expansion prosthesis, permanent expansion
      prosthesis, latissimus dorsi myocutaneous flap associated with an implant, rectus
      abdominis myocutaneous pedicle flap, free flaps.

PMID- 9768144
TI  - [Silicone breast implants and breast cancer].
AB  - The authors discuss the immunological and oncological risk of prefilled silicone
      gel breast implants. A comparative study of 146 patients undergoing breast
      reconstruction by silicone implant at the Institut Gustave-Roussy and 146 matched
      controls demonstrated the absence of any difference between the two groups
      concerning survival, local recurrence rate and metastases.

PMID- 9768145
TI  - [Breast reconstruction after breast cancer: a review of a 12-year-long
      experience].
AB  - The experience of 428 mammary reconstructions (MR) performed by the same surgeon,
      evaluated more than two years after surgery, enable the authors to try to
      determine possible correlations between results of MR and methods employed.
      Antibiotic prevention and tissue expansion only appear to have a significant
      influence on MR issue, whereas capsular contracture and aesthetic result did not
      seem correlated with prior radiotherapy or texture of the wall implant. This
      study confirms the low morbidity of MR. As regards quality of life, MR provides a
      noticeable benefit to a wide majority of patients. No method has been proved to
      be higher, or not advisable, against others. So, indications must be modulated in
      every case, patronizing better compromise between safety, quality and stability
      of morphologic result, and need expressed by each patient.

PMID- 9768146
TI  - [Breast reconstruction with the autologous latissimus dorsi flap. Preliminary
      report of 60 consecutive reconstructions].
AB  - Many women who have undergone or will undergo mastectomy request breast
      reconstruction and feel that it is an important part of their total cancer
      treatment. Autogenous tissue methods take a place more and more important in
      breast reconstruction. The autologous latissimus dorsi flap, is a recent method
      of autologous breast reconstruction. We have done a retrospective study based on
      a series of 60 consecutive reconstructions operated between march 1993 and april
      1995. The advantages of the autologous latissimus dorsi flap are the same of the
      others autologous breast reconstruction methods: the reconstructed breasts are
      soft and match an opposite normal breast more successfully than those made with
      implants. The disadvantages of this technique is mainly the dorsal seroma that
      was observed in 70% of cases but was easily managed by aspirations. The
      aesthetics results have been judged by two surgeons as very good in 85% of cases,
      good in 11.6% and low in 3.3%. The satisfaction rate of the patients in high:
      86.6% are pleased and 13.3% are satisfied. The autologous latissimus dorsi breast
      reconstruction is a safe and reliable technique and provides an excellent
      alternative to the TRAM flap, when the patient prefer the dorsal donor site or
      when there are some risk factors to do a TRAM flap. Finally this technique bring
      a major advance in the field of breast reconstruction, immediate or delayed.

PMID- 9768147
TI  - [Complications and abdominal wall sequelae in pedicle TRAM breast
      reconstruction].
AB  - The doubts concerning silicon implants since 1991 have led to the development of
      autologous tissue reconstruction and especially pedicle rectus abdominis flap
      (TRAM). The good cosmetic results obtained on the reconstructed breast also
      promoted the development of this technique. However, the complications and donor
      site sequelae must not be underestimated. The abdominal wall is considerably
      modified in terms of muscle strength and residual scars. It can be the site of
      complications such as herniae and scar necrosis. In order to more accurately
      assess these risks, the authors studied a series of 251 TRAM breast
      reconstructions performed at the Institut Gustave-Roussy between 1982 and 1992.
      The rate of herniae requiring reoperating decreased considerably with improvement
      of the technique, falling from 10% to less than 2% in the most recent cases, with
      a mean rate of 7% for the overall series. Infraumbilical scar necrosis was not
      exceptional, but the incidence appeared to decline with the surgeon's experience
      (about 5%). This depended on the patient's clinical context, especially a history
      of smoking. The strength of contraction of the upper segment of the muscle was
      significantly decreased and the cosmetic results of the abdominal scar were not
      always favourable as they were considered to be satisfactory in only 70% of
      cases. This study demonstrates the importance of not underestimating the sequelae
      of donor site scars, which must be taken into account when evaluating the results
      of the technique.

PMID- 9768148
TI  - [Functional evaluation of the abdominal wall after raising a rectus abdominis
      myocutaneous flap].
AB  - Breast reconstruction with transverse rectus abdominis muscle (TRAM) flap raises
      two contradictory questions: the vascular safety of the flap and the late
      abdominal wall sequellae. In order to analyse these sequellae, 71 patients with
      TRAM flap breast reconstruction at the Institut Curie had a late postoperative
      evaluation by both a physiotherapist and a surgeon, an average 28 months after
      their reconstruction. 12 had had a double pedicled TRAM (DPT) and 59 a single
      pedicled TRAM (SPT). Hernias and bulges were systematically recorded, and all
      patients had an evaluation of their abdominal wall function by questioning
      (subjective evaluation) and muscular testing (objective evaluation). The overall
      hernia rate (including bulges) was 5.6%. This rate was 2.5% when mesh was used,
      and 9.5% when direct closure was performed. This hernia rate was not influenced
      by the type of TRAM (SPT or DPT). 20% of patients complained of residual
      abdominal pain, and 36% of a decrease of their abdominal strength after SPT. Both
      these figures were 75% after DPT. Testing showed that these sequellae were
      related to an impairment of the supraombilical portion of the rectus, this
      impairment being much higher after DPT than SPT: none of the 12 patients with DPT
      were able, from a lying position, to sit down without using their hands (not
      reaching 4 in Lacote's test), whereas 47% of the SPT could do it. The oblique
      muscles were also impaired, as less than 20% of patients reached Lacote 4.
      However, this impairment was not influenced by the type of flap harvested.
      Testing was also equivalent after both techniques of SPT (standart or
      "supercharged"). The post-operative hernia rate was not higher for DPT and seemed
      related to the technique used for abdominal wall closing (mesh vs direct
      closure). However, the functional sequellae (pain, muscle strength decrease) were
      much higher after DPT than SPT. It thus confirms us in our attitude to restrict
      the indications of DPT, when feasible, to the profit of microsurgical flaps.

PMID- 9768149
TI  - [Rectus abdominis free flap breast reconstruction. A series of 23 cases].
AB  - Free TRAM flap breast reconstruction was performed in 23 patients from july 1993
      through november 1995 at the Saint-Louis Hospital in Paris. The surgical team was
      composed of eight different surgeons. In all cases a delayed breast
      reconstruction procedure was performed. All patients in this series had
      previously received radiation therapy and 82.6% patients presented with excess
      body weight. Decision to perform a free flap procedure was confirmed
      peroperatively under two conditions. Adequate caliber of the donor and recipient
      vessels was required, allowing the anastomoses to be performed without
      magnification in most cases. Preservation of the thoraco-dorsal vessels was the
      rule so as to allow later use of a latissimus dorsi flap if necessary. Thus in 8
      of the 31 cases in which a free flap was initially indicated a pedicled flap was
      actually performed so as to satisfy the above conditions. All procedures were
      performed by two surgical teams working simultaneously. Flap harvest met local
      tissue requirements in all cases. A lateral strip of rectus abdominis muscle and
      fascia was preserved when this appeared feasible. The abdominal wall was
      reinforced by prosthetic means in 82.6% of cases. The average operative time was
      9 hours. Results were considered satisfactory or very satisfactory in most cases.
      The complication rate was 39.1%. Among the complications noted were 1 case of
      partial flap necrosis, 1 case of fat necrosis, 1 abdominal hernia, 1 abdominal
      bulge (both abdominal complications occurred in patients in whom no prosthetic
      material was used for abdominal repair). This complication rate also includes
      revision of the microsurgical anastomoses in 2 cases; in both cases the flap
      survived completely. This study tends to suggest that the free TRAM flap for
      breast reconstruction is a reliable technique. It is the authors' belief that it
      should replace the bipedicled TRAM flap since it combines ample flap
      vascularization with minimal rectus harvest.

PMID- 9768150
TI  - [Preservation of the muscle in the use of rectus abdominis free flap in breast
      reconstruction: from TRAM to DIEP (Deep inferior epigastric perforator) flap.
      Technical notes and results].
AB  - The advantages of TRAM (Transverse Rectus Abdominus Muscle) flap for breast
      reconstruction is now well recognised. This technique allows a cosmetic
      reconstruction with a more natural shape than with conventional reconstruction
      with prosthesis. However the disadvantage is the need of removal of part or all
      rectus abdominis muscle. If the techniques of free flap are now recognised to be
      more reliable than pedicle TRAM they have not demonstrate a superiority in term
      of parietal sequellae. To avoid such problem some teams have progressively
      developed the DIEP (Deep Inferior Epigastric Peforator Flap). This flap is
      harvested only on the transmuscular perforators. We are presenting here our
      expertise which progressively has leed us from free partial TRAM to DIEP. From
      december 1995 to january 1997 we have practice 18 breast reconstructions with
      free flap. On 13 DIEP we had only one parietal complication due to incomplete
      closing of the aponeurosis at the lowest part of the surgical approach. This
      complication was easily corrected as the muscle was still tonic. On 5 TRAM,
      clinical examination finds parietal weakness on 3 cases. We believe that this
      technique is full of promises as it brings autologous tissue with no complication
      on donor site.

PMID- 9768151
TI  - [Mammoplasty for symmetry of the contralateral breast and its oncologic value].
AB  - Controlateral occult carcinomas are observed in 3 to 5% of the reduction
      mammaplasty of the controlateral breast at the time of the breast reconstruction.
      The symmetry procedure allows a good check up of the glandular tissue of the
      controlateral breast, especially when there is no evidence of tumor. The
      different techniques of breast reduction provide specific possibilities for such
      exploration and should be chosen according to the area which should be explored.
      The superior pedicle technique gives us the best exposure and an easier
      modelling. It gives a good aesthetic results in 80% of cases. The central pedicle
      and dermoglandular pedicle technique give a good exposure and permits us to fill
      the defect with glandular flap. The drawback of the inferior pedicle technique is
      the lack of control of the central and inferior quadrant.

PMID- 9768152
TI  - [Role of plastic surgery in the conservative treatment of breast cancer].
AB  - Conservative surgery (CS) is widely accepted today as the treatment of choice for
      60 to 80% of the primary breast cancer. Esthetic results of CS are not good in
      all the cases and improvement can be obtained thanks to the remodelling of the
      breast after tumorectomy. The scar should be selected according to the location
      of the tumor; the glandular tissue should be reshaped using local glandular flaps
      or following the principles of the reduction mammaplasties. Tumorectomy located
      in the upper part of the gland can be reshaped with an inferior pedicle type of
      mammoplasty. Defect located in the inferior part of the gland can be
      reconstructed with a superior pedicle mammoplasty. These sophisticated
      tumorectomies are providing good esthetic results on the reconstructed breast but
      require commonly a symmetry procedure on the contralateral breast. Such
      contralateral reduction allows a better exploration of the opposite breast and
      histological examination of the reduction specimen. In a series of 76 CS
      performed at the European Institute of Oncology (IEO), which were associated with
      some kind of plastic procedure to lower the risk of bad cosmetic results
      (representing 25% of the CS associated with plastic surgery), we confirmed the
      value of the mixed oncologic and plastic approach. The esthetic results observed
      in this series are better than those observed in another series previously
      published at the Gustave-Roussy Institute (IGR)--good results: 72% (IEO) vs 50%
      (IGR), and bad results: 6% (IEO) vs 20% (IGR). Statistically such comparison can
      be criticised, specially because of the short follow-up of the Milan series.
      However, the difference is rather important if we consider that the series of
      Milan was a selection of cases with poor esthetic expectation (25% of all the CS
      performed during the same period), while the series of Paris did not select the
      patients in what concerns the risk of poor esthetic result.

PMID- 9768154
TI  - [Internal supporting mammary lamina. Results of the detection of breast lesions].
AB  - In order to stabilize the curves of a surgically remodelled breast, Bustos
      associated to a periareolar mammaplasty a synthetic internal supporting lamina.
      At the beginning, in 1985, a smooth perforated silicone sheet was used. Since
      then, other materials were proposed (radioopaque ou radiotransparent, resorbable
      or not). Because of their superficial situation, in front of the mammary gland,
      it was essential to study the consequences of the presence of such a material on
      the mammographic follow-up. We radiographied all the different types of sheet in
      vitro, and also in vivo, 3 to 19 months after surgery. At the same time we
      studied the modifications in the breast tissue, in 117 patients after surgical
      treatment for ptosis or mammary hypertrophy, using different kinds of incisions
      (periareolar or anchor-shaped, J or L shaped, inferolateral oblique or lower
      vertical incisions). We also studied the effects of mammary implants covered with
      Dacron, since some internal mammary supporting lamina are made with this
      material. The silicone sheet gives some artifacts and may calcify. The resorbable
      sheet has no effects on the mammography. The radiotransparent non resorbable ones
      causes no problems on short terms, but we are not sure whether some
      calcifications appear on long term or not.

PMID- 9768153
TI  - [Cutaneous suspension: immediate breast reconstruction with abdominal cutaneous
      advancement using a non-resorptive mesh. Preliminary results and report of 28
      cases].
AB  - The immediate breast reconstruction with a definitive prosthesis (IBRDP) is the
      most useful technique in our experience. We proposed a technique to allow the use
      of IBRDP also in cases of mastectomy with large skin excision and also to permit
      a better definition of the inframammary fold. The prosthesis pocket is prepared
      as usually with the pectoralis major and serratus anterior muscles and then, a
      skin flap is undermined about 6-8 cm below the inframammary fold to prepare an
      upper abdominal skin flap. The innovation point is the use of a triangular non
      absorbable mersilene mesh to pull up and maintain the flap. The mesh is initially
      sutured at the future inframammary fold projection 4 to 6 cm lower than the
      previous inframammary fold and sutured under tension to the third and fourth
      costal cartilages. The prosthesis is located in front of the mesh and behind the
      muscles. Twenty nine patients had a mastectomy with IBRDP with the "Cskin
      suspension" technique at European Institute if Oncology (IEO) from june 1995 to
      september 1996. Only one case (3.4%) had a prosthesis loss 3 months after the
      surgery, probably by a prosthetic material rejection. This technique permits an
      IBRDF for the patients with a good abdominal skin laxity and also avoids the use
      of a more complicate or a more expensive technique (myocutaneous flaps or skin
      expanders). The small post-operative complications rate must be confirmed by a
      larger follow-up to evaluate the capsular contracture rates and the final
      cosmetic results.

PMID- 9768155
TI  - [A rare breast tumor...].

PMID- 9768156
TI  - [Statistics and breast implants].
AB  - The author presents his point of view concerning the incidents and complications
      of augmentation mammoplasty which he has seen and treated over the 35 years of
      his career. He questions the basis of certain generally accepted ideas,
      prospective analyses deduces from statistics subject to criticism in terms of
      "publicity" or the interests of companies manufacturing breast implants or the
      regrettable incompetence of the authorities supposed to verify the quality of
      these implants.

PMID- 9768157
TI  - [Orbital decompression in exophthalmos due to thyroid disease. Report of 69
      cases].
AB  - Dysthyroid exophthalmos is due to mismatching of the orbit and its contents,
      essentially due to muscle enlargement, and, to a lesser degree, fat volumetric
      changes. Surgical treatment is designed to expand the orbital volume by bone
      removal or to reduce orbital contents by fat removal, or a combination of the two
      techniques. Our series consisted of 69 patients who underwent orbital
      decompression for proptosis, with osteotomy (12 cases) or associated with fat
      removal (57 cases). We obtained good results for all cases, and did not encounter
      any complications. Several factors now appear to play a role in the choice of
      surgical technique, particularly the preoperative radiologic (CT) examination
      which determines the muscular and fat involvement, wall orbital changes and
      appearance of the sinuses. Orbital fat removal seems to be useful in proptosis
      reduction in those cases in which fat is more involved and easy to remove.
      Anthral ethmoidal decompression is the best technique in the case of dysthyroid
      optic neuropathy.

PMID- 9768158
TI  - [Role of coral blocks in cheek augmentation surgery. Prospective study of 23
      patients].
AB  - A two-year multicentre prospective study was performed from 1992 to 1995 in order
      to evaluate the real value of various kinds of coral blocks as bone substitute in
      maxillofacial surgery. This study was supported by the French National Agency for
      Research Valorization (GBM/TEP procedure). Ten Maxillofacial Surgery Units were
      included. During this time, 28 coral blocks (23 patients) of two different shapes
      were used as malar implants for correction of congenital or acquired zygomatic
      hypoplasia. The mean follow-up was 1.8 year (min: 1.5; max: 2). The tolerance was
      perfect for 89% of cases. The radiologic opacity never decreased more than 30%
      and the volume augmentation was always stable at the end of the follow-up period.
      Three implants were removed because of septic complications. Rigid fixation
      between the implant and the zygomatic bone appears to be the most important
      factor of success. On the other hand, the surgical approach (endo- or exo-buccal)
      does not seem to influence the success rate. The aesthetic improvement was always
      evaluated as satisfactory and stable by the patients and the surgeons. The
      authors discuss the real value of the various kinds of biomaterials and
      especially coral, comparing their personal data with those of the literature.
      Coral blocks clearly constitute a safe and reliable bone substitute, but further
      investigations are required to determine its long-term behavior.

PMID- 9768159
TI  - [Posterior marginal mandibulectomy for cancer of the oral cavity and oropharynx.
      Experience with 14 clinical cases].
AB  - Marginal mandibulectomies are now widely performed in the anterior aspect of the
      mandible providing that the preoperative clinical and radiologic evaluation shows
      no bone invasion. These marginal resections can be extended to the posterior
      area. Molar, retromolar and ascending ramus resections can be performed. This
      removes the upper bone segment preserving the dental canal whenever possible.
      From 1990, 14 patients were treated with this technique for carcinoma of the
      retromolar triangle (9 cases) and oropharynx (5 cases). 11 different flaps were
      used to cover the soft tissue defect and 3 direct sutures were performed. Eleven
      patients underwent postoperative radiotherapy with a mean dose of 58 Gray. Median
      follow-up was 32 months. Functional and cosmetic results were very satisfactory
      due to preservation of mandibular continuity. We found no osteomyelitis,
      postoperative fracture or radionecrosis. This technique avoids a segmental
      resection in some well-defined cases and the disability produced as a result of
      this treatment. There is therefore, no need for complex reconstruction and the
      operating time is shortened in fragile patients.

PMID- 9768160
TI  - [Use of deformities in the treatment of facial skin defects in children:
      "deforming resections". Report of 35 cases].
AB  - Spontaneous resolution of deformities after excision of facial skin lesions has
      been known and used for a long time by plastic surgeons. The resorption mechanism
      of deformity is based on natural skin expansion, and seems to be directly related
      to the action of the muscles of facial expression and their skin relations.
      Natural expansion has been shown to be effective in children. Between 1990 and
      1994 excision of skin lesions, including congenital nevi, leading to
      postoperative deformity of the cheek, labial commissure, nose, eyelid and
      forehead, was performed on 35 patients, aged from 3 month to 12 years. The
      average follow-up is 24 months. For 26 patients (74%), natural resorption was
      observed 4 or 6 weeks later with good aesthetic results. For 6 patients (17%),
      the deformity persisted 3 or 6 months later, but did not require any further
      surgery. For 3 patients (9%), a second operation was necessary. Using the skins
      natural capacity for expansion in the treatment of facial skin defects in
      children is a method of reconstruction which has already been used for excision
      in enforced position. The platysma and muscles of facial expression by their
      action on skin mobilisation, allow natural expansion. A better knowledge of
      cutaneous biomechanical properties enables plastic surgeons to find an
      alternative to other classical methods.

PMID- 9768161
TI  - [Mammaplasty with triple interposition of glandular flaps. Technical note].
AB  - The unfavorable breast contours resulting from a reductive mammaplasty or a
      mastopexy influenced the authors into developing a technique that provided
      reduction of the breast base and axillary pole, convenient medial position of the
      lateral pole and substantial conification of the breast tissue to help project
      the areolomamillary complex to the apex of that cone. From March 1987 to May 1996
      two hundred and seventeen operations were performed with this technique that
      consists of construction of three glandular flaps and maximum preservation of the
      skin covering. The results obtained showed to be very satisfactory and more
      lasting.

PMID- 9768162
TI  - [Decubitus ulcers of the buttocks: our therapeutic approach in the course of the
      last ten years. Report of 32 cases].
AB  - The authors conducted a retrospective study of 80 cases of pressure sores of the
      pelvic girdle. This study was designed to evaluate the therapeutic approach,
      surgical reconstruction techniques and their results at 1 year. Only 32 patients
      (40%) underwent surgical reconstruction, always using regional pedicled
      myocutaneous flaps. 15.6% of these patients developed a local recurrence (5/32).
      Analysis of the results of this series shows that failures of reconstruction
      cannot be attributed to surgical techniques, but to their indications. The
      reduction of recurrences depends on earlier medical and surgical management and
      more rigorous patient selection, especially concerning psychological aspects. The
      patient's cooperation is an essential condition to the success of treatment.

PMID- 9768163
TI  - [Distal extensor digitorum brevis muscle flap. Report of 2 cases].
AB  - The authors describe an original technical modification of the extensor digitorum
      brevis muscle flap. As described, its use in a classical reverse flow manner
      allows the flap to reach only the metatarsophalangeal joints. The presence of the
      first dorsal interosseous pedicle offers the possibility to sacrifice the plantar
      anastomoses of the pedis pedicle and raise the flap on the vascular network of
      the first metatarsal space. The point of rotation is moved distally from the apex
      of the first metatarsal space to its base. The length of the vascular pedicle is
      substantially enhanced and enables the flap to cover all dorsal and palmar
      defects of the toes. Two clinical cases are showed. The advantages of this flap
      are discussed, particularly its indication in reconstructive surgery of the foot.

PMID- 9768164
TI  - [Anatomical study of interosseous flaps and the concept of postero-anterior
      interosseous flap. Preliminary report].
AB  - The postero-anterior interosseous flap uses the distal network of the posterior
      and anterior interosseous arteries. With this flap the authors would like to
      point out all the possibilities of reverse fascio-cutaneous flaps offered by the
      interosseus arteries. An anatomic study has been carried out with both a
      literature review and a cadaveric study. The authors studied the distal
      interosseous anatomy on 40 fresh upper arms after colored latex injection of the
      anterior interosseous artery near its origin. A distal anastomosis between
      anterior and posterior interosseous arteries was present in 38 cases. This
      anastomosis was situated at an average of 25 mm from the radio-carpal joint. The
      authors found the fascio-cutaneous artery branch of the anterior interosseous
      flap in 40 cases, but its origin is variable. Therefore, the anterior
      interosseous flap was possible in every case but the pedicle length was variable.
      The surgical technique must begin by a distal exploration of the vascular
      network. After this exploration the flap is chosen in function with the anatomic
      possibilities and the cutaneous defect. The authors have already used several
      kinds of reverse interosseous flap: anterior (6 cases), posterior (11 cases) and
      recently, postero-anterior (2 cases). With the postero-anterior flap the authors
      will show the large range of flap possibilities offered by the interosseous
      arteries for the cutaneous defects of the dorsum of the hand.

PMID- 9768165
TI  - [State-of-the art on rhinoplasty, facial rejuvenation and breast augmentation.
      Antibes, Juan-les-pins, 24-26].

PMID- 9768166
TI  - [Occipital pedicle forehead flap].

PMID- 9768167
TI  - [Skin necrosis after ultrasound lipolysis].

PMID- 9768168
TI  - [Results of biplane face lifts with maximal skin underlining and vertical SMAS
      flap].
AB  - It is difficult to evaluate the medium and long-term results of facelift due to
      loss to follow-up of a large number of patients. The authors developed a
      questionnaire which they sent to their patients. 148 patients (143 women and 5
      men) answers this questionnaire and 54 patients returned for review. This
      subjective evaluation of the results nevertheless had the advantage of
      identifying three target organs specifically treated by the surgical techniques
      used: the nasolabial folds, the jowls and the neck. Improvement or deterioration
      of the results was therefore evaluated and reported on a series of tables. The
      results are analysed in this paper. 70.3% of patients studied reported a
      satisfactory objective result with a mean follow-up of 26.8 months. The least
      favourable results were observed in the neck, due to the small number of
      technical procedures performed on the platysma, which would appear to justify
      greater surgical attention. Among the complications reported, 9.2% of cases
      indicated inadequate results, especially concerning the "lion's wrinkle", which
      emphasizes the value of a complementary endoscopic procedure at this site.
      Perioral wrinkles were a source of dissatisfaction in 14.8% of cases, and can be
      treated by dermabrasion. Lastly, a number of minor complications such as
      malposition of the ear lobe, facial redness or scar abnormalities were also
      mentioned and are easily accessible to an ambulatory secondary improvement
      procedure. This study therefore validated the operative technique of biplane
      facelift with a satisfactory stability of the results over time. Objective review
      of dissatisfied patients, who generally returned for review after receiving the
      questionnaire, led to a number of reoperations, which appear to be useful in the
      case of early deteriorations occurring during the first postoperative year and
      which concern about 5% of patients. The ultimate objective of this paper was to
      try to establish a methodology for the analysis of the long-term results of
      facelift, without directly involving the examiner or operator, who may ignore
      what the patient really feels.

PMID- 9768169
TI  - [Pathogenesis and treatment of the nasolabial fat pad: nasolabial dermolipopexy].
AB  - The author presents an original technique designed to control the nasolabial fat
      pad, which often becomes organized in the form of a fatty tube. Following sub
      adipose facelift, the principle of this technique consists of opening the fat
      pad, then suspending it to the inferior orbital margin by a U-shaped suture
      anchored onto a plastic plate placed on the skin.

PMID- 9768170
TI  - [Isolated cervico-facial liposuction applied to the treatment of aging].
AB  - Almost 20 years after its first application, liposuction is today a procedure
      commonly used on the cervicofacial region. This article emphasizes the importance
      of the isolated liposuction in the rejuvenating treatment of the face.
      Liposuction allows the correction of the fattening of the contours, but also of
      the sagging of the teguments thanks to the skin retraction. The reconstruction of
      a tridimensional image shows the importance and the constancy of the adipose
      tissue in the whole face, even in thin ones. The limits of this method are
      related to the existence of a skin with a sufficient elasticity of a not too
      important skin excess, and of a sufficient subcutaneous adipose tissue. In
      selecting the orientation of the tunnels according to the lines of skin tension,
      we are determining the concept of an orientated skin retraction. In the
      conclusions, the isolated tunnelization of the face, with or without liposuction
      seems to be a solution allowing either to delay for several years the time for
      facelift, or to suggest an alternative choice for patients who refuse or fear the
      principle of a facelift.

PMID- 9768171
TI  - [Silastic implants and reconstruction of the orbital floor: review of twenty
      year's experience].
AB  - Fractures of the orbital floor still raise unresolved therapeutic problems
      concerning the operative indication or the type of material to be used during
      repair. For this purpose, surgeons have the choice between heterologous or
      autologous grafts, implants and numerous biomaterials. The authors conducted a
      retrospective study with a follow-up of 20 years of 137 patients treated in the
      department for a fracture of the orbital floor using a Silastic implant. The
      reoperation rate to remove the implant was 13.8%. Various complications were
      observed: dacryocystitis, migration of the implant to the skin and maxillary
      sinus, cutaneous fistula, persistent diplopia, orbito-sinus communication,
      periorbital cellulitis. In view of these complications, it appears preferable to
      modify the therapeutic approach and propose autotransplantation of the concha for
      defects less than 1.5 cm2 and autologous parietal bone graft for larger defects.

PMID- 9768172
TI  - [Analysis of reconstruction procedures for defects of the mouth floor. Report of
      96 cases].
AB  - The aim of this study was to assess the reconstruction of floor of the mouth
      defects after cancer surgery. The medical records of 140 patients treated between
      January 1st, 1987 and December 31st, 1995 were reviewed. Ninety-six patients had
      primary reconstruction: there were 82 cutaneous or osteomyocutaneous flaps and 14
      microsurgical transfers. Among these patients 15 had titanium mandibular
      reconstruction plates. The reconstruction procedures and postoperative follow-up
      were evaluated. Healing by first intention is appropriate for superficial soft
      tissue defects. The nasolabial flap is used only for small mucosal defects. A
      forearm flap should be the first choice treatment for large soft tissue defects
      owing to its plasticity and reliable vessels. Segmental mandibular resections
      often imply mandibular reconstruction. Titanium plates may be used alone or with
      a cutaneous flap. Tolerance of plates after radiotherapy is very good and they
      are an effective method of reconstruction for fragile patients.

PMID- 9768173
TI  - [Occipital forehead pedicle for one-stage repair of defects of the upper third of
      the face].
AB  - The authors describe a reconstruction technique for defects of the superior third
      of the face using a fascio-cutaneous flap with a forehead paddle supplied by an
      occipital pedicle. This flap has been successfully used in three cases to cover
      defects of the temporo-zygomatic area indeed, the superior part of the cheek. Our
      three patients presented recurrent cutaneous carcinoma, a local and general poor
      condition. This process suits reliability and easiness to a good carcinologic,
      functional and aesthetic result.

PMID- 9768174
TI  - [Osteogenic capacity of a vascularized periosteal flap tubulized around a coral
      implant. Experimental study on sheep].
AB  - The objective of this study was to evaluate the osteogenic capacities of a
      vascularized periosteal flap reinforced by a bone substitute, coral, to validate
      the possibility of creating prefabricated bone flaps with shapes adapted to a
      recipient zone, while limiting the donor site sequelae. 24 periosteal flaps, with
      preserved vascular pedicles, were raised from the medial femoral epiphyses of 12
      ewes. In the same animal, these flaps were reinforced with a cylinder of coral
      and a cylinder of autologous graft. After implantation for 2 or 8 weeks depending
      on the animal, the flaps were submitted to histopathological and
      histomorphometric examination. The results of this examination demonstrated a
      similar course of the flaps regardless of the type of reinforcement, both in
      terms of implant resorption and the quantity of newly formed bone.

PMID- 9768175
TI  - [Large abdominal wall reconstruction by free flap after recurrence of a
      dermatofibrosarcoma protuberans].
AB  - Based on a case of recurrence of a dermatofibrosarcoma protuberans of the
      abdominal wall, the authors discuss the need for initial wide resection of this
      type of skin tumour and the possibilities of repair of extensive full thickness
      defects of the abdominal wall by means of a latissimus dorsi myocutaneous free
      flap.

PMID- 9768176
TI  - [Breast implants and their history].
AB  - The controversy concerning breast implants has led to a profound change in our
      surgical practice. Four years after the moratorium suspending the use of silicone
      implants, the situation still remains confused. Polyurethane implants,
      incriminated as being dangerous at the start of the anti-implant campaign, were
      cleared by the FDA in 1995, but have not been re-released onto the market.
      Silicone implants, the subject of a great many international studies on
      carcinogenicity and immunological risks which failed to confirm these risks, are
      now being used again throughout the world except in the USA, Canada and France.
      Hydrogel implants, victims of the bad reputation of the other implants, were
      suspended for dubious insurance reasons concerning the French Huriet law,
      although they satisfy the clinical and laboratory criteria required for breast
      implants. Only normal saline implants are currently used in France, although
      their safety is only relative, as the reoperation rate for deflation is not
      negligible. In our opinion, the Cronin type of bladder implant is obsolete and
      the new available technologies must be used, although they raise an economic
      problem following the overpublicized silicone implant catastrophe.

PMID- 9768177
TI  - [About prions...].
AB  - Iatrogenic Creutzfeldt-Jakob disease (CJD) was first reported in 1974, in a 55
      year-old woman whose symptoms started 18 months following corneal implant
      surgery. The transplant donor died of CJD. More recently, the epidemy of bovine
      spongiform encephalopathy in the U.K., and the reported cases of iatrogenic CJD
      due to extractive pituitary hormone injections, emphasized the problems of its
      etiology and the way these neurodegenerative diseases get transmitted. A new
      infectious pathogen was described as a prion: "small proteinaceous infectious
      particle", responsible of transmissible neurodegenerative diseases. The lethal
      evolution of these diseases, and the complete absence of preventive procedures
      are fearful regarding the extension of the disease, specially during the
      procedure of grafting originating from possibly infected people whose screening
      is currently impossible. It is mandatory for the surgeon to update its knowledges
      including the legal bylaws regarding a good surgical prevention. One must be
      certain the implant, wether autologous or heterologous, is completely free of
      disease, mainly in aesthetic surgery. This paper attempts to summarise this
      topics. One must bear in mind that the current knowledges could soon turn
      obsolete with a constant progression of scientific research and of the
      epidemiologic data.

PMID- 9768178
TI  - [The Ring test: a good tranquilizer, but a poor predictive test].

PMID- 9768179
TI  - [Fasciola hepatica antigens. Use in the diagnosis of human fascioliasis].
AB  - The ELISA technique was standardized for detecting antibodies against Fasciola in
      25 serum samples from patients-infected with Fasciola hepatica using excretion
      secretion antigens (ESA), tegument antigen and somatic antigen. A study was made
      of serum samples from 46 patients with other parasites such as Ascaris
      lumbricoides, Trichuris trichiura, Entamoeba histolytica, Schistosoma mansoni and
      Giardia lamblia. The cohort value for each trial was established after studying
      100 serum samples from healthy people as negative controls taking as criterion
      the mean optical density plus 2 standard deviations from the mean. Regarding this
      group and using ESA, we obtained specificity and sensitivity.

PMID- 9768180
TI  - [Preliminary study of AP-64 cell line (Aedes pseudoscutellaris) for dengue-1 and 
      2 virus multiplication].
AB  - We study a new arthropod cell line, AP-64, which was obtained from Aedes
      pseudoscutellaris larvae. The best growth and maintenance media are defined,
      testing the adequacy of dengue 1 and 2 viruses which become manifest by the
      appearance of the cytopathogenic effect as syncytiums. The immunofluorescence
      technique is applied to detect early multiplication of those viruses.

PMID- 9768181
TI  - [Excretion-secretion antigens from adult Dirofilaria immitis in the diagnosis of
      human filariasis by solid phase immunoenzyme assay].
AB  - The solid phase enzymatic immuno-assay (ELISA) was normalized for detecting
      antibodies against. Filaria using excretion-secretion antigens (ESA) from
      Dirofilaria immitis adults in a group of asymptomatic and microfilaraemic
      patients infected by different species of filariae (loa loa, Wuchereria
      bancrofti, Onchocerca volvulus, Mansonella ozzardi and Mansonella perstans), and
      in another group of symptomatic and aminorofilaraemic patients, temporary
      residents in an area with endemic loiasis. The ESA-ELISA specificity permitted
      the distinction between filariasic and non-filariasic patients.

PMID- 9768182
TI  - [Some factors that influence acceptance of antimalarial chemoprophylaxis in
      groups exposed to infection].
AB  - 1,100 internationalist workers were surveyed in order to assess the factors
      bearing upon the proper use of antimalarial chemoprophylaxis in endemic areas of
      Africa. We detected difficulties concerning advisin and its quality. Most
      subjects did not begin chemoprophylaxis before leaving Cuba, according to the
      advice. It was proved that one third of them do not observe regularly this
      prophylactic measure.

PMID- 9768183
TI  - [Variation in organophosphate and carbamate insecticide resistance in relation to
      esterase activity in Culex (c.) quinquefasciatus Say, 1823 (Diptera: Culicidae)].
AB  - We determined the existence of the resistance mechanism by means of the esterase
      enzymes in a Culex (C) quinquefasciatus stock established in the laboratory.
      Bioassays were performed with insecticides such as malathion and temephos
      (organophosphoric) and propoxur (carbomate); two cycles were completed during one
      year. Resistance to malathion was higher. The presence of esterase enzymes in
      this stock was determined by using synergits and starch gel and paper filter
      electrophoresis techniques.

PMID- 9768184
TI  - [Physiological age of 2 populations of Anopheles (N.) albimanus Wied., 1821
      (Diptera: Culicidae) and its importance in malaria transmission].
AB  - The physiological age of Anopheles albimanus in two villages of Havana Province
      was studied. In general, we detected a similar pattern of behavior in the
      species, with a higher number of females being born during the dry season, which
      represents a higher risk of malaria transmission in this season.

PMID- 9768185
TI  - [Use of an indirect immunofluorescence probe for early detection of latent
      malaria].
AB  - We followed up the values of the titres of malaria antibodies by the indirect
      immunofluorescence (IFI) technique in 52 patients: 27 Cubans and 25 foreigners
      with malaria. All the subjects had previously been in endemic zones. The
      diagnosis of the disease was based upon the thick drop test. The prevailing
      species was Plasmodium falciparum. The IFI technique was used at the beginning of
      the treatment, weekly and after 3 months. Four patients had recurrences in the 3
      first weeks of the follow-up, with increased levels of the antibody titres before
      parasitaemia appeared. Those titres decreased with the specific treatment. We
      propose that the patients with increasing antibody titres in spite of the
      negative results of the thick drop test be considered as having a risk of
      developing malaria.

PMID- 9768187
TI  - [Isolation and identification of Vibrio genus microorganisms in the Quibu River].
AB  - The Quibu River sewages were studied during 9 weeks, in order to isolate and
      characterize Vibrio genus microorganisms. Twenty Moore's hyssops were placed 2 or
      3 times a week on the banks of the river, where each of them was kept in a
      passive capture stay for 24 hours. In all the hyssops placed, Vibrio cholerae non
      01 were isolated.

PMID- 9768186
TI  - [Esterase patterns in Culex (C.) quinquefasciatus Say, 1823, and its relation to
      malathion organophosphate insecticide resistance].
AB  - This paper describes the esterase patterns found in a wild strain of Culex
      quinquefasciatus which was known to bear resistance genes and the existence of
      genetic polymorphism for such esterases is demonstrated. The most frequent
      polymorphisms found were Est-1, Est-2, and Est-3; Est-2 was possibly responsible
      for Culex quinquefasciatus resistance. The frequency of potentially resistant
      females was significantly higher as compared to males: in addition, the
      hypothesis was proposed that heterozygotie Est-3 is selected as a genotype which
      may contribute to resistance in neotropical areas.

PMID- 9768188
TI  - [In vivo resistance to strains of Trypanosoma rhodesiense, Mozambique, 1985].
AB  - We report the existence of high resistance to Melarsoprol and low resistance to
      Suramin in 11 Trypanosoma rhodesiense species. They were isolated from humans in
      the Tete province, Mozambique, and kept in mice at the Maputo National Health
      Institute. The preliminary results obtained with Suramin administered
      intracranially, are also reported.

PMID- 9768189
TI  - [Ecological parameters of arbovirus circulation on the north coast of Havana. I.
      Collection of culicids in the Guajaibon region].
AB  - We show the culicids collected in the Guajaibon zone, in Havana Province, in
      order to characterize the present population according to ecological parameters
      and the possible risk for man. We show that Aedes scapularis is numerically and
      ecologically dominant over the rest of the species that attack men, as well as
      the possible indirect influence of culicid populations in crab caves upon human
      beings.

PMID- 9768191
TI  - [Shell identification of snail carriers of Fasciola hepatica in Cuba].
AB  - We show the main conchiological characteristics of Fossaria cubensis (Pfeiffer)
      and Pseudosuccinea columella (Say), intermediate hosts of Fasciola hepatica in
      Cuba. Also, their qualification is compared with the species which are confused.

PMID- 9768190
TI  - [Automated sentinel system of infectious diseases in Cuba].
AB  - We state that the creation of the Automated System of Epidemiological
      Surveillance should become an integral part of the Service of Hygiene and
      Epidemiology of the Republic of Cuba, which allows for the operative evaluation
      of the epidemiological situation in the country in order to take timely anti
      epidemiological and prophylactic steps.

PMID- 9768192
TI  - [Determination of glucose-6-phosphate dehydrogenase deficiency to prevent
      possible drug-induced hemolysis].

PMID- 9768193
TI  - [Isolation of hepatitis A virus in tissue culture. Preliminary report].

PMID- 9768194
TI  - [Latin American Association of Mycology].

PMID- 9768195
TI  - [Methodology for the epidemiologic study on acute respiratory infections].
AB  - The foundations and methodology for an epidemiological study on acute respiratory
      diseases are described. The study took place in 4 urban health areas in Havana
      City and 4 rural doctor's offices in Matanzas. A discussion is carried out
      regarding the intervention design for the staff of the health primary assistance
      team headed by the family doctor.

PMID- 9768196
TI  - [Infective capacity of the parasitic nematoda Romanomermis iyengari (Welch, 1964)
      (Nematoda: Mermithidae) in mosquito larvae in natural conditions].
AB  - The effectiveness of the parasitic nematoda Romanomermis ivengari (Welch, 1964)
      was proved in 3 breeding sites of Anopheles albimanus (Wiedman, 1821) and Culex
      Nigripalpus (Theobald, 1901) and 2 spillways for 2 oxidation ponds with Culex
      quinquefasciatus (Say, 1823) larvae, in the Isle of Youth. The results of the
      experiments showed the infesting capacity of this nematoda species with 80-100%
      parasitism in A. albimanus and C. nigripalpus larvae, and 75-80% mortality for C.
      quinquefasciatus. Besides, the recycling capacity of R. invengari, after its
      introduction, was proved, confirming its possible use in the control of mosquito
      larvae of medical-epidemiological importance in the Cuban tropical conditions.

PMID- 9768197
TI  - [Use of a personal computer in the epidemiologic intervention on acute
      respiratory infections].
AB  - A discussion is carried out on the use of a general-purpose personal computer as
      an aid for taking prophylactic and control steps in the face of epidemics due to
      acute respiratory infections.

PMID- 9768198
TI  - [Normalization and application of an ELISA ultramicro for the detection of herpes
      simplex virus antibodies].
AB  - An ELISA ultramicro was normalized for detecting herpes simplex virus antibodies.
      A study was made on 145 samples from the Pedro Kouri Tropical Medicine Institute
      and the Blood Bank, both by ELISA ultramicro and immunofluorescence and ELISA,
      and 98% and 99% of coincidence was reached, respectively. It indicates good
      correspondence between these techniques.

PMID- 9768199
TI  - [Sensitivity of Mycobacterium fortuitum by the broth microdilution method
      determining the inhibitory minimal concentration].
AB  - A study was conducted on 40 Mycobacterium fortuitum strains isolated from
      symptomatic patients suffering from respiratory diseases and skin lesions. Their
      susceptibility to different antimicrobial agents was determined by the broth
      microdilution method, measuring minimal inhibitory concentration. There was
      sensitivity of the strains to gentamicin and tetracycline as well as resistance
      to the tuberculostatic drugs used (isoniazid and ethambutol) and cefalotin.

PMID- 9768200
TI  - [Detection of anti-Histoplasma capsulatum antibodies by the ELISA technique.
      Preliminary study].
AB  - An indirect micro-ELISA system is presented for diagnosing histoplasmosis. The
      diagnostic criteria are defined by using sera from 12 patients who are
      histoplasmosis carriers. For this group, the optical density values were superior
      to 1,000; use was made of 43 sera from blood bank donors and 9 sera from children
      without a history of exposure. The optical density values in these cases were
      inferior to 0,200. The significant difference found led to the diagnostic
      criterion for confirming 3 histoplasmosis carriers who showed clinical
      manifestations but had been negative to double immunodiffusion. Thus, the
      usefulness of the proposed micro-ELISA system for early diagnosis was proved.

PMID- 9768201
TI  - [Knowledge and prejudice about leprosy in Havana City].
AB  - One thousand two hundred sixteen people living in 6 representative municipalities
      in Havana City were surveyed in order to know what they knew about leprosy and
      how these patients are perceived by them. The purpose was to ascertain if the
      community was prepared to help them to their adaptation to a socially useful
      life, which is one of the tenets of the Program for the Control of this disease.
      It was proved that only 10% had the necessary knowledge about leprosy and the
      remaining 90% had wrong notions about it. It is concluded that the community is
      not prepared for bringing about a change in the present status of this condition.

PMID- 9768202
TI  - [Detection of cytomegalovirus in urine using DNA-DNA hybridization].
AB  - A discussion is conducted on the results of the application of the technique for
      hybridizing nucleic acids to the detection of cytomegalovirus (CMV) in urine
      samples. For this purpose, 2 probes from 2 different regions of the genome of the
      AD169 strain of CMV were used. The results were compared with those obtained by
      the technique for the detection of early fluorescent antigens (DEFA) in 2 groups
      of patients at risk of suffering from CMV infections. After assessing the
      usefulness of the two probes in detecting CMV in urine samples, it was shown that
      probe B from the region which codes the synthesis of early viral proteins had a
      coincidence and specificity levels regarding the reference test (DEFA)
      significantly superior to that of probe A. The results of hybridization may be
      ready within 48 and 72 hours. The qualification of the technique fo its
      application to virological diagnosis is discussed.

PMID- 9768203
TI  - [Comparative study of serologic techniques for the diagnosis of human
      leptospirosis].
AB  - A comparative study was carried out in order to assess 3 serological techniques
      employed at the Provincial Centers of Hygiene and Epidemiology for diagnosing
      leptospirosis. The study included 49 sera from patients with leptospirosis
      confirmed by the techniques of passive hemoagglutination (HA), plate macroscopic
      agglutination with thermoresistant antigen (TR) and indirect immunofluorescence
      (IIF). Sensitivity was 90% for HA, 96% for TR and 84% for IIF. IIF was performed
      with the use of 5 different antigens and the highest serological reactivity was
      obtained with the strain belonging to Canicola serogroup.

PMID- 9768204
TI  - [CAMP factor for the differentiation among Aeromonas species].
AB  - The CAMP factor technique, described by Natale Figura as a presumptive method for
      the differentiation of the species hydrophila, sobria and caviae, was applied to
      80 Aeromonas strains isolated from children under 5 years with acute diarrheic
      disease. The typical phenomenon was seen in aerobiosis and anaerobiosis
      conditions in 10 strains, which were classified as Aeromonas hydrophila. In
      aerobiosis conditions/alone, it was observed in 20 strains, which were identified
      as Aeromonas sobria. It was not observed in either of the incubation conditions
      above mentioned in 50 of the remaining strains, which were identified as
      Aeromonas caviae. The advantages of applying this new technique is emphasized.

PMID- 9768205
TI  - [Identification of strains of beta-hemolytic streptococci of groups A, B, C, and
      G by coagglutination].
AB  - A study was conducted on the coagglutination (CoA) technique in the serogrouping
      of betahemolytic streptococci of the groups A, B, C and G, previously identified
      by physiological tests and the agar immunodiffusion technique. This technique was
      used as a reference test and, according to its results, it can be stated that the
      CoA technique allowed for the serological grouping in 95.7% of the strains. The
      CoA technique was assessed by using reactions prepared in our laboratories and
      the commercial kit Phadebact.

PMID- 9768206
TI  - [Detection of anti-Cryptococcus neoformans antibodies in 3 groups of human sera].
AB  - The tube agglutination (TA) technique was normalized in order to determine anti
      Cryptococcus neoformans antibodies, according to Palmer et al., by employing
      positive and negative control sera and an antigenic suspension prepared from an
      autochtonous strain of Cryptococcus neoformans varneofornnans. Three groups of
      human sera were studied and the role of TA in detecting antibodies in the group
      of sera from patients with active cryptococcosis (100%) was shown. In sera from
      banks positiveness was only 6%, while in the group of fowl breeders, considered
      to be "exposed", positiveness was found to be 16%, although with low titres. A
      discussion is carried out about the value of this technique as a complement in
      the diagnosis and prognosis of cryptococcosis.

PMID- 9768207
TI  - [Report on the therapeutic use of rimantadine and amantadine].
AB  - A discussion is carried out about the experiences with the application of
      rimantadine and amantadine to patients with influenza. The basic general results
      consisted in the fact that 2 of the 74 patients treated had a high cure percent
      (> 68.0%) within the first 72 hours after using the drug. No new diseased were
      found among the 40 contacts to whom chemoprophylaxis was applied. There were only
      3.9% adverse reactions among the total number of people treated with amantadine.

PMID- 9768208
TI  - [Field trial of the Cuban recombinant vaccine against hepatitis B (Heberbiovac
      HB). Study in newborn infants born to AgsHB+ mothers].
AB  - A study was conducted on 106 newborns, whose AgsHB positive mothers received
      active protection against hepatitis B (83 with the Cuban-produced Heberbiovac HB
      vaccine and 23 with the Engerix-B vaccine manufactured by S. Kline as control
      group, following the scheme 0, 1 and 2 months with the first dose administered in
      the first 12 hours after birth. Samples were taken to study virus B markers at
      birth (umbilical cord) after 30, 60, 90 and 180 days. Laboratory determinations
      were carried out by the ELISA technique with diagnostic kits from the firm
      Organon Tecknica. Ten or more IU/L of anti-HBs present in serum was considered as
      the lowest protective level. Children were classified according to the AgeHB
      present in mothers, AgsHB in the umbilical cord and the concentration of Ags HB
      in maternal serum. 100% of the children who received the control vaccine showed
      serological evidence of seroconversion to anti HBs with protective titres, and
      the values of the geometric mean of the titres of antibodies were statistically
      significant (p < 0.01) in all the extractions, favoring the Cuban vaccine. The
      efficacy of the two preparations used in this research work was 100%. This study
      makes it possible to report on a recombinant vaccine against hepatitis B
      (Heberbiovac HB) which represents the first vaccine of this type produced in
      Latin America, the efficacy of which was proved in the field trial.

PMID- 9768209
TI  - [Stain hybridization method with pRepHind probe for the diagnosis of Plasmodium
      falciparum].
AB  - A study was conducted on the parasitemia detection level and the specificity of
      the pRepHind DNA probe for diagnosing Plasmodium falciparum by the stain
      hybridization method. The parasitemia detection level was studied by using
      dilutions of a P. falciparum in vitro culture, adjusted by direct microscopic
      examination to 1; 0.1; 0.01; 0.001; 0.0001 and 0.00001% of parasited red cells.
      Specificity was increased by using DNA extractions from P. Yoelii, P. berghei and
      human leucocytes. The results showed that the method was able to detect 0.0001%
      of parasitemia starting from DNA extractions of 100 L infected red cells. The
      pRepHind probe only detected specifically DNA from P. falciparum. It is concluded
      that the method is suitable for being used in the diagnosis of infection due to
      P. falciparum.

PMID- 9768210
TI  - [Use of a dengue anti-complex monoclonal antibody in viral purification].
AB  - The purification of different serotypes of dengue virus from a monoclonal
      antibody which recognizes an epitope present in the four serotypes bond to a
      Sepharose 4B matrix activated with cyanogen bromide, is reported. Results
      evidence that the method employed makes quicker the process of purification with
      a high degree of purity.

PMID- 9768211
TI  - [Serologic marker as indicator of no circulation of poliovirus in Cuba].
AB  - The surveillance of the circulation of the wild poliovirus is an essential
      element for the eradication of poliomyelitis. The Pan-American Health
      Organization emphasises on the etiological study of acute flaccid paralysis in
      order to achieve this aim. The characteristics of our program against this entity
      allowed to use the presence of antibodies in a sample obtained in February from
      the infant population born on July during the previous year as criteria to know
      the circulation of wild poliovirus. In 727 infants studies in the country (5% of
      the total number of births during July), 99.1% showed no antibodies with a titre
      equal or greater than 1:10. Low titres found in 7 infants were considered as a
      remnant from maternal transmission. Results obtained represent a strong evidence
      of the fact that there is no environmental circulation of poliovirus during the
      period which had the greatest incidence of the disease.

PMID- 9768212
TI  - [Obtaining a clone of the AP-61 cell line. Its usefulness in the multiplication
      of dengue viruses 1 and 2].
AB  - The obtention of a clone of the cell line AP-61 (Aedes pseudoscutellaris) is
      reported. Details of the cloning and culture media employed are discussed.
      Usefulness of the clone for the multiplication of dengue 1 and 2 viruses is
      proved in comparison with the original line using the indirect immunofluorescence
      technique.

PMID- 9768213
TI  - [Characterization of monoclonal antibodies that recognize the thermolabile toxin
      of Vibrio cholerae].
AB  - The obtention of two monoclonal antibodies which recognize a single epitope
      present in the subunit B of the thermolabile toxin of Vibrio cholerae and another
      which shows a cross-reaction with those produced by certain enteropathogenic
      toxins, is reported. The standardization of a solid phase indirect
      immunoenzymatic assay (ELISA) for the primary screening and selection of hybrids
      was performed; in addition, the isotype was determined.

PMID- 9768214
TI  - [Phage typing of Mycobacterium tuberculosis using the overlay technique.
      Preliminary study].
AB  - One hundred and fifty strains of Mycobacterium tuberculosis were classified by
      the phagotyping technique, using the double layer method described by Adams and
      modified by Jones. The efficacy of this method was studies in comparison with the
      method claimed by Redmond and Ward and traditionally employed for Mycobacteria
      typing. Preliminary Results obtained have allowed to prove its advantages. A 96%
      of coincidence with respect to the traditional method was reported.

PMID- 9768215
TI  - [Standardization of an indirect ultramicro ELISA for the determination of total
      antibodies against the measles virus].
AB  - An indirect ultramicro ELISA system (UME) for the determination of antibodies to
      measles virus by the cuban technology of Ultramicro Analytical Systems (SUMA) was
      developed. A number of 448 serum samples from the National System of
      Seroepidemiological Surveillance of Measles were simultaneously processed by the
      Ultramicro ELISA system and by the haemagglutination inhibition technique.
      Results were compared in both assays. Afterwards; 120 serum pairs obtained from
      the same source were studies and processed in a similar way. Results evidenced
      the usefulness of such immunoenzymatic system for the serological diagnosis and
      the positive validation of replacing conventional techniques by this novel
      technology.

PMID- 9768216
TI  - [Serologic study for determining the circulation of respiratory viruses in Havana
      City].
AB  - During 1991, 2,400 serum samples from subjects under 15 years, and 2,400 serum
      samples from subjects with the same age or over 15 years were assessed against
      antigens of 7 respiratory viruses by the complement fixation test or by the
      haemagglutination inhibition technique. The results from these investigations
      allowed to determine the little circulation of the respiratory syncytial virus
      which may result in an increase of a susceptible population and the occurrence of
      outbreaks. The endemic state of Adenoviruses was determined and the subtype H1N1
      of influenza viruses was found to have a little circulation with a raise in the
      population under 1 year old age during November. The subtype H3N2 of influenza A
      was the most important agent within the population studied, followed by Influenza
      B virus during September and November. All viral agents were found to have
      circulated in the different age groups of the population assessed.

PMID- 9768217
TI  - [Non-tuberculous mycobacteria isolated in Cuba during the 1985-1989 period.
      Preliminary report].
AB  - A number of 1,061 strains of nontuberculous mycobacteria referred to "Pedro
      Kouri" Institute of Tropical Medicine during the period of 1985-1989 were
      studied. Strains were from Provincial Centers of Hygiene and Epidemiology of the
      country. According to the results obtained, most of the strains classified are
      found in groups III and IV according to the criteria of Runyon (54, 76, and 36%,
      respectively). Species with a greater frequency belong to the complex MAI and M.
      fortuitum.

PMID- 9768218
TI  - [Serologic response to some herpesviruses in a group of HIV infected patients].
AB  - The titres of antibodies to the herpes simplex virus, cytomegalovirus, and the
      antigen of viral envelope of Epstein-Barr virus were determined in serum samples
      from patients infected by the human immunodeficiency virus (HIV) who belonged to
      groups II (n = 26) and IV (n = 32) according to the present Classification System
      of HIV infection, as well as in a group of blood donors (n = 52). The geometrical
      average titres obtained in the different agents were very high in patients having
      HIV infection with respect to the geometrical average titres observed in blood
      donors. Patients from group II had titres to the antigen of viral envelope of the
      Epstein-Barr virus significantly higher than blood donors. Levels of antibodies
      to these agents in patients from group IV were higher than levels obtained in
      blood donors. Differences regarding levels of the antigen of viral envelope of
      the Epstein-Barr virus were highly significant. These results suggest the
      possible relevance of the Epstein-Barr virus infection in the natural history of
      AIDS.

PMID- 9768219
TI  - [Diagnosis of cytomegalovirus infections in patients with HIV infection.
      Comparison of the indirect immunofluorescence and viral isolation techniques].
AB  - The technique for the detection of fluorescent early antigen was compared to the
      classical method of viral isolation in cells from the human lung. The study was
      performed with the use of 85 urine samples from 64 patients presenting with HIV
      infection. The technique for the detection of fluorescent early antigens showed a
      sensitivity of 91%, an specificity of 97%, and a coincidence of 94% with respect
      to viral isolation. The main advantage of the technique for the detection of
      fluorescent early antigens with respect to viral isolation is that the former
      provides a quicker diagnosis of cytomegalovirus infection within 48-72 hours,
      besides being easy to perform.

PMID- 9768220
TI  - [Evaluation of an ELISA for the detection of anti-Aspergillus fumigatus
      antibodies].
AB  - An indirect MicroELISA system for the detection of anti-Aspergillus fumigatus
      antibodies using human anti-IgG conjugated to peroxidase was standardized. Serum
      samples of two patients having an aspergilloma diagnosed by clinical,
      microbiological, and serological criteria were used as positive controls. In
      addition, 119 serum samples of blood donors and 216 serum samples of patients
      having chronic pneumopathies were also studied. The standardized system may be
      used as a diagnostic complement for it is able to discriminate between antibody
      levels (IgG) in different clinical forms of aspergillosis and in those
      individuals having respiratory diseases which may favour the colonization by this
      pathogen.

PMID- 9768221
TI  - [Evaluation of an ultramicroELISA system for the diagnosis of rubella].
AB  - An indirect Ultramicro ELISA assay, previously standardized in our laboratory,
      for detecting antibodies IgG to the rubella virus was assessed in comparison to
      the hemagglutination inhibition technique. This assessment allowed to determine
      its efficacy in the National System for Epidemiological Surveillance of this
      entity. One hundred and ninety serum pairs of clinically suspected cases of
      rubella were studied and a high percent of coincidence (99.4%), specificity
      (99.4%), and sensitivity (100%) was found between both techniques. In addition,
      73 serum samples of blood donors were processed using an indirect microELISA
      system (Berhing) which was compared to the Ultramicro ELISA technique for rubella
      and it showed a 100% of sensitivity, specificity, and coincidence.

PMID- 9768222
TI  - [Establishment of a diploid cell line of human lung (PHuE-1)].
AB  - The obtention of a diploid cell line from human lung of great concern for the
      virological diagnosis and research is reported. Certain aspects about its
      application and characterization are discussed.

PMID- 9768223
TI  - [Applying an ultramicroanalytical system to the diagnosis of infectious
      diseases].
AB  - The multiple applications and advantages of the ultramicro analytical system in
      the serodiagnosis of different diseases produced by viruses, bacteria, and
      parasites are briefly reported. Also, perspectives in the use of this technology,
      not only for the diagnosis, but for the detection of microbial antigens are
      pointed out.

PMID- 9768224
TI  - [Virologic diagnosis of an outbreak of epidemic hemorrhagic conjunctivitis by an
      indirect immunofluorescence technique. Cuba.1989].
AB  - The causative agent of an hemorrhagic conjunctivitis outbreak was assessed
      through the study of 18 conjunctival exudates using the indirect
      immunofluorescence technique and isolation in cell culture of human embryo
      fibroblasts. In addition, 395 paired serum samples were studied and Enterovirus
      70 was found to be responsible for the outbreak.

PMID- 9768225
TI  - [Serologic diagnosis of HIV (1988-1989)].
AB  - Determination of antibodies to HIV virus by the ELISA technique was performed in
      27,652 serum samples from January 1988 to November 1989. Samples which were
      positive twice underwent the Western Blot technique. A 0.41% of positiveness to
      the virus was found in 1988 and a 0.34% in 1989. Confirmation of positive cases
      by Western Blot was statistically significant in 1989.

PMID- 9768226
TI  - [Inhibition of the multiplication of a Coxsackie A9 strain isolated from a
      patient with epidemic neuropathy by the interferons alfa and gamma].
AB  - We present the results of the in vitro action of alpha and gamma interferons and
      of Intacglobin and Igegam against the 47/93/IPK (Coxsackie A9) strain isolated
      from the cerebrospinal fluid of a patient with epidemic neuropathy. The in vitro
      studies showed that the two interferons inhibited the replication of this agent;
      they also showed the presence of antibodies to it in the Intacglobin and Igegam.
      The results attained demonstrated that the use of these compounds could be
      effective for the treatment of this entity.

PMID- 9768227
TI  - [Detection of immunoglobulin A in serum and saliva of patients with hepatitis A].
AB  - Specific secretory serum IgA antibodies to the hepatitis A virus from samples
      from patients with clinical symptoms compatible to hepatitis A, their contacts,
      and healthy subjects were analyzed using an ELISA technique; results were
      compared with those of specific serum IgM antibodies to the hepatitis A virus.
      The following results were attained in 175 blood samples: coincidence by 98.8%;
      sensitivity by 96.8%; and specificity by 100%. Two cases were negative to IGA and
      positive to IGM. On comparing the presence of IGA in saliva with the presence of
      IGM in blood, coincidence was of 88.1%; sensitivity, of 40.9% and specificity, of
      100%. Of the 22 cases with positive IGM in blood, only 9 showed specific IGA
      antibodies in the saliva. The 111 cases who had negative IGM in blood were also
      negative to IGA. The obtained data suggest that specific serum IGA antibodies to
      the hepatitis A virus are an indicator of a recent or occurrent infection due to
      this virus and thus it may be considered and alternative for the diagnosis of
      this disease.

PMID- 9768228
TI  - [Importance of Tarebia granifera in the control of a population of Biomphalaria
      peregrina introduced in Cuba].
AB  - It was observed that the Tarebia granifera plays a significant role in the
      control of a Biomphalaria peregrina population introduced in a permanent water
      body. The densities of this planorbid, which had reached high levels, were
      notably reduced by two important events: an increase of the water level due to
      heavy rains, and the introduction of the competitor, whose effectiveness had been
      tested in a different habitat. Knowledge on the ecology and biology of the
      competitor and the host in permanent water bodies helped to elaborate the
      measures of control which led to the reduction of the host densities while those
      of the competitor increased.

PMID- 9768229
TI  - [Capacity of the eggs of the larva-eating Rivulus cylindraceus fish, Poey 1860,
      for resisting desiccation. Possible use as a bioregulator of mosquito larvae in
      temporary reservoirs].
AB  - The capacity of the eggs of the Rivulus cylindraceus larvivorous fish to resist
      partial desiccation for a certain period of time is described. It was
      demonstrated that while the normal development of the eggs last for approximately
      14 days, the maximum time of permanence out of the water was of 70 days. Some
      characteristics of the R. cylindraceus, which place it among the annual fishes to
      be used as biological control agents, are described. The use of R. cylindraceus
      as bioregulator in permanent as well as temporary reservoirs is proposed.

PMID- 9768230
TI  - [Effect of cypermethrin on some reproductive factors in Culex (C)
      quinquefasciatus Say 1823].
AB  - An experiment was carried otu with a Culex quinquefasciatus strain with
      resistance genes called "Quibu", and with a susceptible strain provided by the
      WHO; they were pressured with different lethal doses of cypermetrine. Time
      mortality regression lines of the 2 strains were estimated following WHO
      methodology and the "Quibu" strain showed tolerance to the insecticide. TL30 and
      TL70 were selected to test their effect on fecundity, fertility, sexual index,
      and egg eclosion time. A significant reduction in fecundity and fertility was
      observed in the "Quibu" strain after it was pressured, no effect was detected on
      the sexual index and egg eclosion time in this strain.

PMID- 9768231
TI  - [Design of a curve model for the detection of human immunoglobulin G against
      herpes simplex virus in ultramicroELISA from a single serum dilution].
AB  - The use of a curve model in the application of a ultramicroELISA technique for
      the detection of human immunoglobulin G against herpes simplex virus is reported.
      Based on end point titration (linear regression) of 100 initial sera, 51 of
      these, with r2 > 0.98, were selected, and 4 curve models were elaborated to
      relate the natural fluorescence logarithm for 4 dilutions with the previously
      determined natural end point titration logarithm. The curve corresponding to the
      1:40 (r2 = 0.9645) was selected to evaluate 39 additional serum samples whose
      approximate titration was known through the graphic design of the 4 dilutions. An
      89% coincidence was found regarding the latter. Divergence of the other 11% was
      due to the lack of accuracy of the graphic method in the points near the cutline.

PMID- 9768232
TI  - [Anatomy and morphometry of Physa cubensis Pfeiffer, 1839 (Pulmonata: Physidae)
      in Cuba].
AB  - The anatomic description of Physa cubensis, based on specimens collected in 5
      different sites in Cuba, is presented. The anatomic characteristics of the
      reproductive system as well as mantle digitations give ground for affirming that
      this is a unique species with external morphological variations and thus it
      should be kept under the Physa genre. Besides, dispersion diagrams and regression
      lines of the length in the width were analyzed in the five sites; the L/A
      (length/width) variation quotient was compared using a variance analysis.
      Significant differences were observed in the different sites probably due to the
      feeding sources of each biotope.

PMID- 9768233
TI  - [Outbreaks of hepatitis A in the City of Havana in the year 1991].
AB  - Fifty-six outbreaks of hepatitis A infection were studied in City of Havana
      between January and September, 1991. In 34 of these, the presence of the
      hepatitis A virus (HAV) was confirmed, either by the detection of specific serum
      IGM antibodies to the HAV or by the detection of the antigen in the feces of the
      subjects under study. Diagnosis was not made in some of the outbreaks due to the
      insufficient number of samples sent to the laboratory. Of the 453 blood serum
      samples under study, 126 were positive for IGM antibodies to HAV (27.8%): a there
      was a good correlation between the presence of this immunoglobulin and the levels
      attained by the alanyl aminotransferase enzyme (ALT). Only in 19 feces samples,
      of the 263 under study, was the HAV antigen detected, which accounted to 7.2%; it
      was demonstrated that this marker is not useful for the diagnosis of an outbreak
      of hepatitis A infection.

PMID- 9768234
TI  - [Behavior of abiotic factors and rhythm of emission of cercaria of Fasciola
      hepatica in Fossaria cubensis in transmission sites].
AB  - Sampling of Fossaria cubensis, main host of Fasciola hepatica in Cuba was carried
      out in 3 transmission sites. A higher mollusk density was found in dairies
      numbers 6 and 9, coinciding with the higher values of total hardness and
      carbonate hardness. Ammonium, nitrite, and nitrite ions showed lower values in
      dairy number 6. Temperature and pH did not show significant differences in the 3
      biotopes. The mollusks of dairy number 6 began to emit cercarias on the 26th day
      after being collected; they showed an emission peak at 9 a.m. and an average of
      60 cercarias emitted by each mollusk at that time of the day.

PMID- 9768235
TI  - [Mechanisms of resistance to organophosphate insecticides, carbamates, and
      pyrethroids in populations of Musca domestica L. (Diptera: Muscidae)].
AB  - Resistance to organophosphorus insecticides (malathion, chlorpyriphos, pyrimiphos
      methyl); carbamates (propoxur); and pyrethroids (permethrin, deltametrine,
      cypermetrine, and lambda cialotrine) was studied in field populations of Musca
      domestica; results were compared with a susceptible reference strain. The method
      of topic application was employed in the bioassays; the synergist effect of the
      s,s,s tributyl phosphorotrioate and of the piperonyl butoxide (PB) was also
      tested. Biochemical microplate tests were also carried out to determine the
      presence of esterase and acetylcholinesterase enzymes in the three populations.
      Generalized resistance to malathion (FR = 264.6; 164.0; 154.7) was observed.

PMID- 9768236
TI  - [Use of the herbicide diquat for the control of the aquatic plant Pistia
      stratiotes and its importance in the control of mosquitoes (Diptera: Culicidae)].
AB  - The feasibility of the use of the Diquat herbicide (reglone) in the control of
      the Pistia stratiotes aquatic plant is tested. This facilitates the reduction of
      mosquito larva densities by the action of natural enemies present in the
      ecosystem. The associated fauna is not affected by the employed concentrations of
      the herbicide under these conditions.

PMID- 9768237
TI  - [Craniofacial dysmorphism in pediatric AIDS. Presentation of a case].
AB  - The case of a five-year-old mulatto girl with craniofacial dysmorphism, infected
      with AIDS virus, is presented. The girl had ocular hypertelorism; eyes slanted
      upwards; increase of the distance between the internal and external canthi;
      prominent triangular philtrum; thick lips; prominent forehead; flat nasal bridge;
      large parotid glands, which indicate that the infection must have transmitted
      during fetal life. These features were not observed in children infected with
      AIDS through other ways such as perinatal transmission, blood transfusions and
      breastfeeding.

PMID- 9768238
TI  - [Bilateral tubo-ovarian abscess caused by Enterobius vermicularis. Presentation
      of a case].
AB  - We present the case of a 33-year-old patient who had undergone hysterectomy due
      to an in situ carcinoma of the uterine cervix; exploratory laparotomy was carried
      out for a suspected abscessed pelvic tumor. It was confirmed that the two
      Fallopian tubes and ovaries were abscessed and exeresis was carried out. The
      anatomicopathological study of these showed granulomas containing gravid female
      specimens of the Enterobius vermicularis species.

PMID- 9768239
TI  - [Study of the relationship dengue-pregnancy in a group of cuban-mothers].
AB  - The current worldwide situation of dengue infection, and particularly in the
      American continent, is analyzed taking into account the increasing risk for
      infection during pregnancy which exists in endemic areas; the consequences of an
      eventual vertical transmission of the virus are practically unknown yet. We
      studied 59 women who gave birth to their children between 5 and 9 months after
      the "peak phase" of the type 2 dengue virus epidemic which broke out in Cuba in
      1981. Sera of the mothers and newborns were studied through various serologic
      techniques in order to detect antibodies; in some cases we tried to isolate the
      virus, without success, from serum samples taken from the newborns; among these,
      we found 4 cases with positive IgM. These newborns showed neither apparent fetal
      damage at birth nor further alterations in a follow-up carried out when they
      reached 5 years of age. The need of carrying out further studies contributing to
      establish an adequate management of pregnant women infected by dengue virus is
      discussed.

PMID- 9768240
TI  - [Determination of complement-fixing antibodies to respiratory syncytial virus.
      Longitudinal study in a population of less than 1 year of age in the City of
      Havana].
AB  - Respiratory syncytial viruses (RSV) are considered among the most important
      agents causing acute respiratory infections in infants below 1 year of age. A 10
      year longitudinal study of monosera from children under 15 years was carried out;
      1,069 monosera from children under 1 year were studied using the RSV antigen
      complement-fixing technique. It was observed that there were short or longer
      periods between the peaks of positive sera and when they were compared with
      medical care reports, they showed correspondence with increased numbers of
      medical care reports. A typical seasonal pattern in the distribution of
      antibodies was determined and this corresponded to the month of February,
      suggesting that this is probably due to the circulation of the virus and not to
      maternal antibodies. The results attained give grounds for considering the
      possible circulation of RSV in our country.

PMID- 9768241
TI  - [Development and evaluation of an ELISA for the detection of IgM antibodies
      against the hepatitis A virus].
AB  - We present the results of the normalization of an IgM capture ELISA method for
      the diagnosis of type A viral hepatitis with reagents produced in the laboratory
      and its comparison with the "Diag-A-Hep" commercial ELISA. The results attained
      were: sensibility by 91%; specificity by 100%; and coincidence of the two systems
      by 97%. Results are discussed and their relationship with clinical symptoms and
      epidemiological characteristics is established. The results attained in 13 serum
      samples taken from patients seen during 2 acute viral hepatitis outbreaks agreed
      with clinical findings.

PMID- 9768242
TI  - [Evaluation of an ELISA for the serologic diagnosis of tuberculosis].
AB  - The use of an ELISA method for the serological diagnosis of tuberculosis was
      assessed through the study of the presence of circulating IgG antibodies to PPD
      in 220 serum samples. An 82% sensibility was determined in 50 serum samples from
      patients with pulmonary tuberculosis, and a specificity of 95.33% in 150 serum
      samples from apparently healthy subjects. 20 serum samples from patients with
      disorders other than tuberculosis were included in the study to determine
      possible cross reactions.

PMID- 9768243
TI  - [Effectiveness of VA-MENGOC-BC in children from 0 to 5 years of age in Cuba.
      First year of observation].
AB  - The effectiveness or post-license efficacy of the BC antimeningococcal vaccine
      (VA-MENGOC-BC) was assessed 1 year after the end of the immunization campaign in
      children aged 0 to 5 years. Occurrence of the disease before and after
      intervention is described and effectiveness is estimated following the
      recommendations described by Orenstein et al. We used 2 case definitions to
      compare results in groups formed following different criteria, according to the
      employed diagnostic tests. Two formulas are used to assess efficacy: one,
      estimating the rates among vaccinated and non-vaccinated; and the other one,
      estimating the ratio of cases per vaccinated population. The increase of the
      relative annual decrease of the incidence occurring since 1985--a decrease of 10%
      or less--which in 1990 reached 34.6% should be stressed; the ratio of new cases
      prevented by the intervention was higher than 75%. Effectiveness or post-license
      efficacy was close to 90%, independently from the case definition variant or
      formula employed.

PMID- 9768244
TI  - Prevalence of Toxocara canis in dogs in the City of Havana.
AB  - A study on the prevalence of Toxocara canis in domestic dogs of City of Havana
      was carried out for the first time in Cuba. 22 dogs were selected in each
      municipality, totalling 330 as the study universe. Dogs' feces samples were
      processed through direct examination using Willis' flotation method (1921). The
      results attained showed a 17.9% prevalence of Toxocara canis, a high figure
      constituting an important risk factor for transmission to humans. This was
      influenced by the age of the animals and the hygienic conditions of the houses,
      significant factors from the epidemiological point of view. Sex did not play a
      significant role.

PMID- 9768245
TI  - [Study of the molluscicide activity of different plants on Biomphalaria
      havanensis, potential intermediary host of schistosomiasis in Cuba].
AB  - Various experimental studies were carried out with plants of the Compositae,
      Verbenaceae, Polygonaceae and Agavaceae families to determine their molluscicidal
      capacity. Molluscicidal activity on Biomphalaria havanensis was detected in
      plants of the Agavaceae family. The plants employed in the experiment were Agave
      fourcroydes and Agave franzosinii. Lethal doses were determined. These were: LD50
      = 12.45 and LD90 = 22.88 mL/L, for A. fourcroydes and LD50 = 8.78 and LD90 =
      15.91 mL/L, for A. franzosinii. No decrease was observed in the effectiveness of
      the aquous extracts with the passing of time. Solar radiation did not seem to
      effect the molluscicidal activity of the plant extracts.

PMID- 9768246
TI  - [Determination of resistance mechanism in Culex quinquefasciatus Say 1823 and its
      operational implication in the correct use of insecticides for its control].
AB  - Resistance to organophosphorous insecticides such as malathion, chlorpyrihos, and
      pyrimiphos-methyl; pyrethroids such as deltametrine and lambda cialotrine; and
      the propoxur carbamate was determined in 4 strain of Culex quinquefasciatus of
      the Eastern, Central and Western parts of Cuba. The increase of esterase enzymes
      was the main mechanism involved in resistance, followed by altered
      acetylcholinesterase (AChe). Gene frequencies were high for esterases (1), and
      moderate for acetylcholinesterase (0.52) in the four strains under study, as an
      average. Bioassays showed resistance to malathion and propoxur. The use of DEF as
      esterase inhibitor showed that pyrimiphos-methyl was not affected by this
      mechanism of resistance, and chlorpyriphos was slightly affected. After 5 years
      of using pyrethroids such as deltametrine and lambda cialotrine, these are still
      useful agents for the control of C. quinquefasciatus; the alternate use of these
      and pyrimiphos-methyl or chlorpyriphos could prevent the development of
      resistance in a short or medium term.

PMID- 9768247
TI  - [Application of a mermithid nematode for the control of mosquito larvae in
      natural conditions].
AB  - Field tests were carried out with the Romanomermis culicivorax nematode (Ross and
      Smith, 1976) for the control of 3 mosquito species--Anopheles albimanus
      (Wiedeman, 1821): Culex nigripalpus (Theobald, 1901); and Uranotaenia saphirina
      (Oster-Sacken, 1868)--in 10 natural reservoirs. The infective nematodes were
      disseminated in doses of 1 x 10(3) preparasites/m2 of surface area. Increased
      infestation indices were observed with values ranging from 1.2 to 3.4; mortality
      percentages fluctuated between 70 and 97% depending on the mosquito species found
      in the reservoirs. In those reservoirs containing specimens of the 3 species,
      anophelines showed more susceptibility to parasite infection; culicines showed a
      lower susceptibility in general. Mosquito larva populations were significantly
      reduced in the treated reservoirs.

PMID- 9768248
TI  - [Buruli ulcer in the Amansi West district, Ashanti Region, Ghana. The Cuban
      experience. I].
AB  - A study was made on 105 patients with Buruli ulcer in the Amansie West district,
      Ashanti Region, Ghana, representing 37.6% of the registered patients. The
      Tontokrom neighborhood showed the highest prevalence: 84 x 1,000 inhabitants.
      Predominance of females (54%) was observed. 74.8% did agricultural work and only
      3 reported a previous trauma, predominantly with one lesion. Household contacts
      were identified. Coverage with the BCG vaccine was low. It is concluded that
      there has been a real increase of the prevalence of Buruli in the region during
      the last years, especially among children and women. This has become a serious
      problem due to its invalidating and irreversible sequelae. Measures of control
      are proposed.

PMID- 9768249
TI  - [Report pf the first case of lymphogranuloma venereum (LGV) in an HIV
      seropositive patient in Cuba].
AB  - The most important clinical and epidemiological aspects of the lymphogranuloma
      venereum as a sexually-transmitted disease are described. We present a summary of
      the clinical history of an HIV-positive patient who presented with a tumoral
      lesion in the inguinal region presumptive of lymphogranuloma venereum. The
      diagnostic value of the polymerase chain reaction (PCR) technique for the
      establishment of an accurate diagnosis is stressed the epidemiological importance
      of the report of this sexually-transmitted disease in an HIV-positive patient for
      the first time in Cuba is also pointed out. A good response was attained with
      Doxycycline.

PMID- 9768250
TI  - [Resistance to organophosphate, carbamate, and pyrethroid insecticides in
      Blattella germanica (Dictyoptera: Blattellidae) in 2 municipalities of the City
      of Havana].
AB  - We determined the resistance of 2 Blattella germanica strains collected in 2
      municipalities of City of Havana--Playa (P) and Centro Habana (CH)--to six
      insecticides: malathion, pyrimiphos-methyl, propoxur, cipermetrine, deltametrine,
      and lambda cialotrine. The P strain showed resistance only to deltametrine (FR =
      80); the CH strain was susceptible to propoxur and lambda cialotrine and
      resistant to malathion (FR = 12), pyrimiphosmethyl (FR = 13), cipermetrine (FR =
      16), and deltametrine (FR = 100). Gene frequency of increased esterases and of
      the modified acetylcholinesterase was determined in the 2 strains. The values of
      increased esterases in the two collected strains were: P = 0.90; and CH = 0.91.
      Values of the modified acetylcholinesterase in the two strains were: P = 0.47;
      and CH = 0.12.

PMID- 9768251
TI  - [Establishment of a subline of C6/36 adapted to growing in a serum-free medium
      and its usefulness for studies on the dengue virus].
AB  - Using the C6/36 clone of the Aedes albopictus cell line, a derived cell line was
      obtained capable of growing in a commercial serum-free medium facilitating this
      line to keep its morphologic characteristics and adhesion capacity. The growth
      speed rate reduction of the adapted cell line was compensated by its low
      maintenance cost. Its usefulness in the multiplication of dengue viruses 1 and 2
      was tested; the reported line showed the same susceptibility for the 2 agents
      than the original cell line when the indirect fluorescence technique was applied.

PMID- 9768252
TI  - [Indirect ultramicroELISA for the detection of total adenovirus antibodies in
      human serum].
AB  - An indirect ultramicroELISA method was normalized for the detection of total
      antibodies to Adenovirus (AD) (UMELISA AD). The optimum concentration of surface
      antigen determined was 30 micrograms/mL; serum dilution was of 1:40; and
      conjugate dilution, of 1:1,000. The UMELISA AD was compared with the complement
      fixing and indirect immunofluorescence techniques. Results showed accordance by
      88% and 96.6%, respectively. The method is valid for the screening of antibodies
      in seroepidemiological studies as well as for the diagnosis of the infection by
      paired serum samples.

PMID- 9768253
TI  - [Ampicillin resistance mediated by the R plasmid in strains of Shigella
      flexneri].
AB  - Forty Shigella flexneri strains isolated from children attended to at the
      Children's Hospital of Camaguey during an outbreak of acute diarrheal disease
      were studied; the minimal inhibitory concentration of ampicillin was determined.
      33 strains (82.5%) were resistant to higher concentrations: 8 to 16
      micrograms/mL, and 7 were susceptible to 4 micrograms/mL concentrations.
      Resistance plasmid (R) extraction was carried out in all the isolated strains and
      a common plasmid was found this plasmid was purified and transferred to
      Escherichia coli HE 101. Resistance transmission was tested.

PMID- 9768254
TI  - [Hematologic-nutritional study in children predisposed to infection with high
      load of Trichuris trichiura].
AB  - A coproparasitological survey is carried out in 3 family doctors' home-offices in
      City of Havana Province following the Kato-Katz technique (3 samples from each
      person); we found 15 children predisposed to high-load infection by Trichuris
      trichiura. This group was compared to a group of 20 children infected with a low
      parasite load, and to another group of 20 children with no parasite infection. A
      study of nutritional anemia was carried out to all of them including: hemoglobin,
      hematocrit, ferritin, serum iron, vitamin B12, and serum and erythrocyte folates.
      No significant differences were found in the mean values of the hematologic
      parameters under study in the various groups, all values being within normal
      limits. All the children under study had normal anthropometric-nutritional index
      values. Based on the results attained, we suggest that the reported anemia in
      individuals infected with a high load of T. trichiura is not only due to parasite
      infection; other factors may influence on it, probably a certain concomitant
      protein-energy deficiency.

PMID- 9768255
TI  - [Study of the seroprevalence of toxocariasis in an infantile population in the
      City of Havana].
AB  - A serological study to detect antibodies to Toxocara canis in a group of 156
      healthy children from City of Havana is reported for the first time in Cuba. An
      ELISA method was employed using excretion/secretion antigens obtained in our
      laboratory. Data on epidemiological factors surveyed in this group are presented.
      Positivity percentage was of 5.2%. Results are discussed.

PMID- 9768256
TI  - [Fecundity and embryonal development of Romanomermis culicivorax].
AB  - Romanomermis culicivorax (Ross and Smith, 1976) eggs completed the late
      preparasite curling phase of their embryo development in an average time of 11
      days and at a temperature of 25 +/- 2 degrees C. It was also observed that female
      R culicivorax specimens laid 312 eggs in 13 days, when male and female specimens
      were placed in a substrate of distilled water with a pH = 4.5.

PMID- 9768257
TI  - [Effect of primaquine on the elimination of sexual forms of Plasmodium falciparum
      in vivo].
AB  - A study was made on 49 patients, carriers of sexual forms of Plasmodium
      falciparum, verified through thick smear tests, who received 45 and 90 mg of
      primaquine base in different schedules selected at random. None of the employed
      schedules proved better than the traditional one of 45 mg base in a unique dose,
      although the schedule of 45 mg on the first and third days showed a slight
      reduction of the time of elimination of the parasitemia. Thus, further studies
      are recommended. No other factors showed an influence on the time of elimination
      of the parasitemia.

PMID- 9768258
TI  - [Status of insecticide resistance in 4 strains of Musca domestica collected in
      animal farms].
AB  - Resistance to insecticides made from different chemical compounds were studied in
      4 strains of Musca domestica collected from 2 poultry farms and 2 cow farms
      following WHO methodology. A high resistance to malathion was observed
      (resistance factor values ranging from 102X to 252X), and moderate, to diazinon,
      fenthion, dichlorvos, DDT, and propoxur. Resistance to the deltametrine and
      permethrin pyreturins was not observed.

PMID- 9768259
TI  - [Effect of 3 organophosphates on the reproduction of Culex quinquefasciatus Say
      1823].
AB  - An experiment was carried out with a Culex quinquefasciatus strain with
      resistance genes called "Quibu", this strain was pressured with 3
      organophosphorous insecticides: malathion, chlorpyriphos, and pyrimiphos-methyl.
      The most toxic for this species was the chlorphyriphos (LC50 = 0.000009 mg/L),
      followed by pyrimiphos-methyl (LC50 = 0.00026 mg/L), and malathion (LC50 = 0.0035
      mg/L). Larvae surviving the effects of the LC30 and LC70 of the three
      insecticides were selected to test their effect on fecundity, fertility and
      sexual index. Fecundity was not affected by the employed doses of chlorpyriphos
      and pyrimiphos-methyl, while a significant decrease was observed with the LC30
      and LC70 of malathion. The employed doses of malathion did not affect fertility
      but there was a slight decrease with the LC70 selections of chlorpyriphos and
      pyrimiphos-methyl. The proportion of adult females showed a significant increase
      with the doses of chlorpyriphos and pyrimiphos-methyl; sexual index was not
      affected by malathion.

PMID- 9768260
TI  - [A computer program for the geographic distribution of fluvial mollusks of
      medical interest in Cuba].
AB  - The need to know the distribution of mollusks considered to play an important
      medical role in Cuba through a geographic representation motivated us to develop
      a software capable of acting as a system for the retrieval of geographic
      information in which the requested data would be presented in maps. The system
      has been called DMIM and it is a useful tool for malacological studies, and
      assessment and planning of programs for the control of intermediate host
      mollusks, as well as for teaching purposes.

PMID- 9768261
TI  - [Normalization of an ultramicroELISA for the detection of antibodies against
      human Parvovirus B19].
AB  - An ultramicroELISA (UME) method was normalized for the detection of antibodies to
      serum human parvovirus B19. The optimum antigen concentration determined was 400
      ng/ml, serum dilution was of 1:100; and the conjugate work dilution was of
      1:2,000. 11 paired serum samples were also evaluated and antibodies were
      detected. The usefulness of the analyzed system is discussed.

PMID- 9768263
TI  - [Biological aspects of Blatella germanica (Dictyoptera: Blattellidae) in
      laboratory conditions].
AB  - In a study of Blatella germanica (L) 1767 (Dictyoptera: Blattellidae) carried out
      in laboratory conditions, 6 nymphal stages were found in a period of 114.71 days,
      at 29 +/- 1 degrees C and 80-90% of relative humidity. Times of appearence and
      eclosion of every ovipositted ootheca, as well as the offspring average of each
      one, were determined. Females ovipositted up to 5 oothecas during their life. The
      maximum average of eggs found per ootheca was 29.22. The average longevity of
      males was lower that that of females (77.23 and 98.40 days, respectively) (t =
      2.21; p < 0.05).

PMID- 9768262
TI  - [3 combinations of esterases and their relation with the resistance to
      organophosphate, carbamate, and pyrethroid insecticides in Culex quinquefasciatus
      Say, 1823 (Diptera: Culicidae) in Cuba].
AB  - The possible relationship between different patterns of esterases and the
      resistance to various types of insecticides was analyzed by bioassays,
      biochemical tests, and electrophoresis carried out in a population of Culex
      quinquefasciatus from Camaguey and in three colonies obtained from it by family
      selection. The original population was heterogeneous and presented 8 combinations
      of esterases in polyacrylamide gel. A3A6B6, B1B6 and B1A6B6 were the most
      frequent of them and characterized each selected colony. Every studied colony,
      including the parental one, showed different levels of resistance to diverse
      insecticides. Only the resistance to propoxur showed less variation. In every
      colony it seems to exist a combination of resistance mechanisms; however, the
      differences found in tests with DEF synergized insecticides show that the
      different bands of zymograms may represent esterases contributing in a different
      way to resistance.

PMID- 9768264
TI  - [Effect of lethal doses of plants of the Agavaceae family on the cardiac activity
      and oviposition of Biophalaria havanensis (Mollusca: Planobidae)].
AB  - Work was carried out with lethal doses of 3 agavaceas, Agave legrelliana, Agave
      fourcroydes and Agave franzosinii, and it was determined the influences of LD50
      and LD90 of agavaceas on the cardiac activity reduction. As a result, it was
      found that A. fourcryodes has the aqueous extract influencing the most on the
      reduction of heart rate. LD90 of agavaceas also affects the embrionary
      development of eggs having between 1 and 7 days of oviposition. The greatest
      affectation was found among the first. A. fourcroydes and A. legrelliana,
      respectively, influence the most on the reduction of the amount of eggs. The
      number of eggs ovipositted by mollucs surviving the application of LD90 from A.
      franzosinii is lower, as well as the number of hatched eggs.

PMID- 9768265
TI  - [Influence of growth development inhibitors on the reproduction of Musca
      domestica (Diptera: Muscidae)].
AB  - An experiment with a strain of Musca domestica susceptible to insecticides and
      treated with different doses of 2 insects' development inhibitors: Juvenon and S
      31183, was carried out. These compounds were added to food supplied to third
      stage larvae. On calculating dosage-mortality lines, it was found a greater
      biological activity in S-31183. Those surviving DL90 were selected for fecundity
      and fertility studies. The following crossings were carried out: treated females
      x treated males, treated females x untreated males, untreated females x treated
      males, untreated females x untreated males (control group). In both compounds it
      was observed a remarkable reduction in the production and eclosion of eggs, on
      comparing the first three crossings with the control group. As regards fecundity,
      sex influences were not observed, whereas fertility was more affected by treated
      females. No differences were found in connection with the survival of all types
      of crossings. Morphological affectations are reported in pupae and adults.

PMID- 9768266
TI  - [Mass breeding of Romanomermis culicivorax (Nematoda: Mermithidae) in the
      tropical conditions of Cuba].
AB  - To develop the process of mass production on a large scale of the parasite
      nematode Romanomermis culicivorax Ross and Smith, 1976, under the control
      tropical conditions of Cuba, it was taken into consideration the standardization
      of a certain number of variables, such as: utilization of eggs in the process of
      infectation, dosage, types of water, types of substrate, temperature, culture
      methods, and storage methods of culture batches. High performances in nematoda
      and approximately the same amount of females and males were obtained when
      mosquito larvae of the species Culex quinquefasciatus Say, 1823, were exposed to
      parasite's infective larvae.

PMID- 9768267
TI  - [Meningococcal disease and VA-MENGOC BC in minors less than 1 year of age. Cuba,
      1983 to 1991].
AB  - A study of the chronological series of mortality due to meningococcal disease in
      children under one year old, the group of highest incidence during the last
      epidemy in Cuba, was carried out. Data were collected by doing a survey in an
      uniform way since 1983 throughout the country. More than 90% of the population
      between 3 months and 5 years old were vaccinated with VAMENGOC BC since the end
      of 1988 until April, 1990. The behaviour of this disease was studied in order to
      identify the influence of this vaccine. It is stressed that the mortality
      incidence reached its epidemic achme in 1986 and begins a slow descence which is
      accentuated in 1990 and 1991, with an annual relative decrease of 26.1 and 34.9%,
      respectively. The highest mortality rate was found in 1984, with a significant
      reduction in 1990 (-23.8%) and 1991 (-41.8%), after the culmination of the
      vaccination campaign with VA-MENGOC BC. It was detected that morbimortality,
      which is lower in children under one month because of the probable protection
      provided by maternal antibodies, started to increase until the fifth month of
      life, when it is observed a trend towards the reduction of morbidity and
      mortality. According to the present immunization chronogram, overall protection
      in only attained after the sixth mont of life.

PMID- 9768268
TI  - [New solid culture media for growing Borrelia persica and Borrelia microti].
AB  - A new solid means for the fast detection of Borrelia persica and Borrelia microti
      is described. Generally, culture and isolation of Borrelia takes about 21 days.
      The serological test, which is carried out more often, takes less time but it is
      associated with false positive reactions relatively high. However, our new solid
      means reduces the culture time to 72 hours, allowing to have a fast diagnosis of
      the disease caused by Borrelia persica and Borrelia microti, and to start the
      early treatment of these patients.

PMID- 9768269
TI  - [Validation of a ultramicroELISA for detecting antibodies against hepatitis B
      surface antigen].
AB  - The results of a validation study of the ultramicroanalitical assay for the
      detection of antibodies against the hepatitis B surface antigen (UMELISA anti
      HBsAg), which was carried out by comparing the results obtained with the
      Hepanostika anti-HBsAg, commercial diagnosis kit are presented. For this purpose,
      sera from the clinical assays of the Cuban recombinant vaccine against hepatitis
      B were used. With the first sera group (n = 30) it was obtained, 93.1% of
      sensitivity, 98.5% of specificity and a concordance of 94.3%. The correlation
      coefficient showed a similar trend of the results (p < 0.01) and no significant
      differences were found in the average geometrical titre (TPG) between both assays
      (p > 0.05). With the second group (n = 100), whose assays were carried out at the
      "Pedro Kouri" Institute of Tropical Medicine (PKI) and at the Immunoassay Center
      (IAC) simultaneously, it was observed a sensitivity of 96.25% in both centers, a
      specificity of 75% at the PKI and of 90% at the IAC, and a coincidence of 92% and
      95%, respectively. The correlation coefficient presented similar values and there
      were no significant differences between the TPG obtained by the two methods (p >
      0.05). The results attained show in general the validity of the new assay and the
      feasibility to put it into practice either for following up the infection, or for
      carrying out clinical assays of vaccine evaluations.

PMID- 9768270
TI  - [Aeromonas hydrophila pneumonia associated with a traffic accident. Report of a
      case].
AB  - The case of a patient who was driving a car after getting drunk is presented. His
      car turned over and he fell into an irrigation canal, and, as a result, he
      suffered from an incomplete drowning syndrome. He was admitted in the Intensive
      Care Unit with acute inflammatory pneumonia and a strain of Aeromonas hydrophila
      was isolated in blood. The patient's evolution was favorable. It is the first
      report on a case like this in our country.

PMID- 9768271
TI  - [Direct sequencing of an amplified product from a serum sample].
AB  - It is reported the nucleotide and amino acidic sequence of a great variability
      region in the dengue 2 virus genome, starting from the RNA of the original virus
      with no passage in the isolation systems. It is compared with the first strain of
      dengue 2 isolated during the 1981 epidemic with 4 passages in lactating mouse.
      Results show that the nucleotide sequence of serum and of strain A15 are the
      same.

PMID- 9768272
TI  - [Anomalous response of antibodies in rash-causing viral infections].
AB  - 20 pairs of sera from the National System of Seroepidemiological Surveillance of
      the triple viral vaccine received in the laboratory with febrile rash diagnosis
      were studied. By using the hemagglutination inhibition test, it was observed an
      abnormal answer of antibodies to both rubella and measles through a falling of
      the antibody titre in one or both diseases, or in one of them with seroconversion
      to the other one. With the aim of defining the existence of a possible polyclonal
      activation already described in literature, it was decided to study the antibody
      response to family Herpesviridae (HSV, EBV, CMV, VZV). 80% of answer to these
      viruses were found. The results are submitted and discussed.

PMID- 9768273
TI  - [Evaluation of a Dot ELISA for the detection of a Rotavirus antigen].
AB  - An evaluation of a Dot ELISA made by the Center of Genetic Engineering and
      Biotechnology for detecting Rotavirus antigen, was carried out. 100 feces samples
      were analyzed by this technique and the results were compared with those obtained
      with polyacrylamide gel electrophoresis, technique traditionally used in the
      Rotavirus diagnosis. It was obtained a high coincidence, specificity and
      sensitivity among them.

PMID- 9768276
TI  - [Taxonomic study of species of the Mycobacterium genus isolated in Cuba].
AB  - 40 strains of the Mycobacterium genus corresponding to 12 species, which were
      subjected to 62 microbiological and biochemical tests, were studied. Each one was
      considered as a character. As a result of the similitude coefficient and their
      grouping, 9 phenomes represented by: Phenome I (Mycobacterium fortuitum), Phenome
      II (MAI Complex), Phenome III (Mycobacterium phlei), Phenome IV (Mycobacterium
      triviale), Phenome V (Mycobacterium smegmatis), Phenome VI (Mycobacterium
      gordonae), Phenome VII (Mycobacterium szulgai), Phenome VIII (MAI Complex), and
      Phenome IX (Mycobacterium scrofulaceum), were obtained. The strain identification
      work was consistent with grouping from the phenotypic point of view.

PMID- 9768275
TI  - [Effects of 3 insecticide formulations in the removal and hatching of oothecae of
      Blatella germanica (Dictyoptera: Blattellidae)].
AB  - Different insecticide formulations used for the control of German Cockroach,
      Blatella germanica (L.) were studied to know their effects on the gravid females
      of this species. The insecticides assayed were baygon 20% EC, diazinon 60 EC, and
      licon 2.5% EC. Exposure to each insecticide showed an effect on the oothecal drop
      (p < 0.001). Gravid females treated with baygon had the highest percent of
      oothecae detached (71%); whereas diazinon caused the lowest percent (33.5%).
      Doses of baygon, diazinon, and icon used showed that among the oothecas detached
      hatching occurred only in 19.01%; 34.2% and 39.11%, respectively. Of the oothecas
      retained by treated females, the lowest hatching percent was produced by baygon
      (13.79%) compared with diazinon and icon insecticides, which presented the
      highest hatching percentages with 39.84 and 47.82, respectively. Therefore, the
      effects of insecticides on females bearing oothecas may be considered at the time
      of selecting an insecticide to control the German cockroach.

PMID- 9768277
TI  - [Report of drug resistance in strains of Mycobacterium tuberculosis isolated from
      patients in Iran].
AB  - 6,472 clinical samples of patients with tuberculosis suspicion between March,
      1993 and March, 1994, were studied. Positive results were obtained in 443
      patients; 238 females (53.7%) and 205 males (46.3%). The predominant age group
      was that between 30 and 39 years (31.5%). The cutaneous test of sensitivity to
      the purified protein derivate (PPD) was positive in 178 patients with a range of
      10-14 mm. Abnormal radiological images were found in 222 patients (50.1%). Higher
      resistance frequency was detected in Mycobacterium tuberculosis strains among
      cases suffering from pulmonary tuberculosis. 42 (9.5%) strains were resistant to
      isoniazid and 31 (7.0%) to streptomycin. Resistance to one drug was observed in
      25 isolations (5.4%). A few strains (1.3%) were resistant to 3 drugs, and 1 of
      them to 5 drugs. Clinical and epidemiological data suggest that resistance to
      drugs in tuberculosis is becoming an important problem in the region. The fast
      diagnosis of this infection and the use of antibiotics with a reduced spectrum
      may enable the control of this form of tuberculosis.

PMID- 9768278
TI  - [Purification of the natural 24kd (P24) of the type-1 human immunodeficiency
      virus (HIV-1) using immunoaffinity].
AB  - The use of systems to detect the presence of 24kd protein as well as the levels
      of antibodies to it, is very useful in the follow-up of HIV-1 infected
      individuals. To develop these systems it is necessary to have this protein
      purified. The present paper describes the purification of p24 starting from the
      semipurified viral flattening on saocaharose gradient, using immunoaffinity
      chromatography with monoclonal antibodies coupled to Sepharosa 4B activated with
      cyanogen bromide. For the characterization of the purified product it was used
      polyacrylamide gel electrophoresis with silver staining and
      immunoelectrotransference. As a result, it was obtained p24 which can be used for
      the development of diagnostic tools and monoclonal antibodies.

PMID- 9768279
TI  - [Estimation of IgG Adenovirus antibody titers using a standard curve and an
      indirect ultramicroELISA essay].
AB  - It was possible to standardize a procedure which combined an indirect microELISA
      assay with a standard curve and that allowed to estimate the titre of IgG
      antibodies to Adenovirus in samples of human serum, using only one dilution of
      these. Based on the end-point titre previously determined for a panel of 117
      serum samples, we selected 90 of these samples (r2 = 0.98) to build 4 standard
      curves that related the natural logarithm of the fluorescence responses to the
      natural logarithm of the end-point titre for a wide range of serum dilutions
      (1:40 = 1:320). It was selected the curve corresponding to serum dilution 1:40
      (r2 = 0.81), which made possible an optimum utilization of those accessories
      designed to handle the volumes in the ultramicro range and, therefore, the
      automation of the whole procedure. The results obtained as regards the complement
      fixation test (100% of sensitivity and 97.3% of specificity) support the use of
      this method in our laboratory as a complementary tool to carry out
      seroepidemiological studies on a large scale and with diagnostic ends.

PMID- 9768280
TI  - [Surveillance of St. Louis encephalitis, Eastern equine and Western equine in the
      province of Ciego de Avila].
AB  - Serological studies were carried out using the haemagglutination inhibition and
      neutralization tests so as to know the circulation dynamics of some arboviruses
      with the use of Western and Eastern equine encephalitis antigens and St Louis
      encephalitis antigens in human serum from sound and symptomatic individuals, as
      well as from sentinel birds, between 1987 and 1991, and during 1994. 1.7% of the
      asymptomatic subjects tested presented neutralizing antibodies to to Eastern
      equine and 4.8% to St Louis encephalitis. 16 patients with seroconversion by
      haemagglutination inhibition to St Louis virus were detected. Surveillance of
      sentinel birds showed that during 1988, 1989, and 1994. St. Louis circulated in
      the municipalities of Moron, Bolivia and Chambas; whereas in the latter the
      Eastern equine encephalitis circulated in 1988 and 1989. Antibodies to Western
      equine encephalitis were detected in sound individuals by haemagglutination
      inhibition due seemingly to heterologous antibodies, since there were no
      neutralizing antibodies against this virus.

PMID- 9768281
TI  - [Genetic relatedness of the dengue 3 virus isolated in the outbreak of dengue
      hemorrhagic fever in Nicaragua, 1994].
AB  - It is reported the isolation of 2 dengue strains, 3 in samples from Nicaraguan
      patients suffering from dengue with hemorrhagic manifestations, which showed the
      reintroduction of this serotype in the region after being 17 years out of
      circulation. It is also reported the genetic characterization of the isolated
      strain, which, according to its classification, belongs to the group of dengue 2
      strains isolated in Southeast Asi and which have been associated to hemorrhagic
      dengue. These results suggest the origin of this strain.

PMID- 9768282
TI  - [Enterovirus meningoencephalitis in the last 5 years].
AB  - The results of the study of Enterovirus as viral meningoencephalitis producing
      agents, carried out from 1990 to 1994, are described, 546 feces samples, 95
      cerebrospinal fluids and 1,058 matched sera were studied and obtained from 1,388
      patients clinically diagnosed with this disease. Samples for viral isolation were
      inoculated into two different cellular systems. The highest number of isolation
      was found in diploid cells from human fibroblast. Antibody determinations were
      carried out by a neutralization test (micromethod) with 11 Enterovirus antigens
      (Echo 4, 6, 9, 11 and 30; and Coxsackie B1, 2, 3, 4, 5 and 6) and in epidemic
      periods with the isolated virus. During the years under study, 2 epidemic
      outbreaks took place: on caused by Coxsackie A9 (1990-1991) and the other one by
      Echo 30 (1994). A greater positivity to Echo 6 and 11 was found among the matched
      sera.

PMID- 9768283
TI  - [Purification and proteic characterization of a Cuban strain of the hepatitis A
      virus].
AB  - The purification and protein characterization of one of the Cuban isolated
      strains of hepatitis A virus was carried out. For this, it was necessary to
      separate the virus from the infected cell by extraction steps with detergents,
      concentration by ultrafiltration and finally, ultracentrifugation in
      saccharosoglycerol discontinuous gradient. Protein concentration, as well as the
      antigenic activity in the different fractions of the gradient were determined.
      For the protein characterization of the microorganism, those fractions with the
      greatest specific activity were analyzed by polyacrylamide gel electrophoresis
      and by Western blotting. It was shown that the viral material was purified and
      concentrated in the last fractions of the gradient. Bands corresponding to the
      structural proteins of hepatitis A were observed through electrophoresis and
      Western blotting.

PMID- 9768284
TI  - [Urethritis caused by serotype B Haemophilus influenzae. Report of a case].
AB  - A case of a patient with schistosomiasis haematobium history, from Mozambique, is
      presented. This patient was admitted in the Institute of Tropical Medicine for
      having urination troubles and purulent urethral secretion. Serotype B Haemophilus
      influenzae, biotype i.v. of the urethra, was isolated. The strain was sensitive
      to ampicillin, chloramphenicol, ceftraxione, and norfloxacin, and resistant to
      tetracycline and erythromycin. The patient got better after receiving treatment
      with norfloxacin. A comment is made on the role of this microorganism as a sexual
      transmission pathogen.

PMID- 9768285
TI  - [ELISA identification of agents causing light cytopathic effect isolated during
      the neuropathy outbreak in Cuba, 1991].
AB  - Using as a reference the strain 44/93 isolated during the neuropathy epidemic in
      1991 and characterized as a producer of a light cytopathic effect (L-CPE), it was
      possible the standardization of an ELISA for the fast identification of other
      strains with similar effect. The assay consisted in a sandwich-type ELISA where
      the conditions selected for each reactive (10 micrograms/mL for the coating
      antibody, 1 mg/mL for the antigen, and dilution 1/2,000 for the conjugate)
      allowed to have an adequate discrimination between the antigen and the antigen
      control for the reference strain used. The evaluation of a panel of reference
      viral strains and of other L-CPE producing strains showed a 100% of coincidence
      between this method and the isolation in cellular culture. The results obtained
      permit us to recommend the use of this assay as a more precise alternative to
      identify these agents.

PMID- 9768286
TI  - [Subgroups classification of strains of the respiratory syncytial virus isolated
      in an outbreak in Ciudad de La Havana].
AB  - A high number of acute respiratory diseases was detected among children under one
      year admitted in a hospital of Havana City. 25 respiratory syncytial virus
      strains were obtained from 93 patients studied. Viral isolations were multiplied
      in HEP-2 cells and after observing a cytopathic effect of 80%, they were
      classified into subgroups by the indirect immunofluorescence technique, using
      anti-protein G antibodies from the respiratory syncytial virus. All the samples
      studied were classified within subgroup A. It is the first time a study like this
      is conducted in our country, which allowed us to deepen into the viral cause of
      these diseases and to know that the subgroup A of the respiratory syncytial virus
      circulated during the outbreak.

PMID- 9768287
TI  - Gastroduodenal inflammation associated with Helicobacter pylori infection.
      Diagnostic and therapeutic implications (a review).

PMID- 9768288
TI  - Saprophytic and cycloheximide resistant fungi isolated from golden hamster.
AB  - Healthy hair samples from golden hamsters were examined for the presence of
      dermatophytes and non-dermatophytes using baiting technique and direct
      inoculation. Thirty-four species and 2 varieties attributed to 17 genera were
      recovered. Paecilomyces variotii (isolated from 84.4% of the examined hair) and
      Aspergillus niger (81.3%) were the more frequent isolates on Sabouraud's dextrose
      agar (SDA) without cycloheximide. Our results have clearly demonstrated that the
      hair of hamster was free from true dermatophytes. Using the dilution plate method
      many fungal species were isolated from cage material (7 genera and 10 species + 1
      variety); from faeces (10 genera and 17 species); from standard chow (3 genera
      and 6 species) of hamster. P. variotii which was the most frequent fungus in the
      preceding 3 substrates was completely absent in the presence of cycloheximide in
      SDA. The present study has demonstrated for the first time the isolation of
      Trichophyton rubrum from hamster faeces. Also, several saprophytic and
      cycloheximide resistant fungi were isolated. In the air of hamster cage
      Cladosporium cladosporioides, Penicillium chrysogenum, Alternaria alternata and
      Scopulariopsis brevicaulis were the most dominant species on SDA with or without
      cycloheximide. Using the agar diffusion method, Aloe sap, onion oil, garlic bulb
      extract and aqueous leaf extracts of Andropogon citratus, Euphorbia sp. and Ruta
      graveolens were tested for their antifungal activity on 10 fungal species. It was
      observed that onion oil exhibited a high inhibitory effect against most of the
      tested fungi.

PMID- 9768289
TI  - Follow up of clinical, laboratory, and serological findings of adult Hungarian
      hospitalized acute hepatitis patients and characteristics of recovery.
AB  - Follow-up features of acute viral hepatitis were evaluated of 210 hospitalized
      adult patients. HA, HB, HC, and NON A-C H were diagnosed in 68 patients, 84
      patients, 22 patients, and 36 patients, respectively. Post-hepatitis syndrome was
      shown in about 20.6%, 19%, 45.5%, and 25% of patients with HA, HB, HC, and NON A
      C H, respectively. At three months, the recovery was shown in about 61.7%, 69%,
      13.6%, and 63.9% of patients with HA, HB, HC, and NON A-C H, respectively.
      Factors of sex, age, and severity of acute phase had no effect on the protracted
      rate in all types, except in HB. After six months, the disease remained active in
      1.5%, 6%, 69%, 8.3% of patients with HA, HB, HC, NON A-C H, respectively. Factors
      of sex, age, severity of acute phase had no effect on the chronicity rate in
      different types, except HB. It was more significantly more frequent in males,
      elderly persons, and mild acute phase in chronic HB cases. Diabetes mellitus was
      also significantly more frequent in chronic HB cases. Flat pattern of ALT
      elevation was significantly more frequent in chronic HB and NON A-C H cases.

PMID- 9768290
TI  - Effect of trace element combination on the immune response of rats treated with
      cytostatic drug.
AB  - The effect of trace element combination, Beres Drop Plus (BDP) on the immune
      response of rats following single treatment with cytostatic drug (5-fluorouracil,
      5-FU) was tested. Animals were treated with 5-FU and SRBC simultaneously, but
      separately. Rats were pretreated with BDP for 21 days. The body and spleen
      weight, furthermore the number of spleen cells and antibody producing cells were
      determined. The antibody titres in blood serum were also measured. The immune
      system of rats, 5 days following the 5-FU treatment, showed considerable
      regeneration. Pretreatment of rats with BDP had a beneficial effect on all
      parameters investigated.

PMID- 9768291
TI  - Effect of different carbon sources on the production of amylase by Bacillus sp.
      MD 124.
AB  - An extracellular, thermostable salt tolerant amylase has been obtained from
      Bacillus sp. MD 124 which was previously isolated from municipal garbage. Among
      the carbon sources used for amylase production, rhamnose, starch, glucose,
      lactose, galactose, maltose and sucrose favoured enzyme production whereas
      sorbose suppressed the enzyme production. Maximum amount of enzyme (15 unit/ml
      culture broth) was produced after 24 h of incubation at 45 degrees C in the
      medium containing 0.5% starch, at pH 6.5. The effect of temperature, pH as well
      as effect of metal ions on enzyme activity was also studied.

PMID- 9768292
TI  - Partial inhibition of amplifications by primers of EHEC genes.
AB  - Diagnostic value of multiplex polymerase chain reaction (PCR) was examined by
      using three primer pairs, specific for the common conserved region of stx1 and
      stx2, eae and an enterohaemolysin A gene (ehxA). The sensitivity in respect of
      each amplicon decreased with three exponents comparing to the individual PCR
      reactions. These PCR reactions were partially inhibited by the presence of
      certain additional primers. This inhibitory effect was template-concentration
      dependent, and was partially balanced by usage of increased amount of dNTP. Taq
      DNA polymerase in a range of 0.3-1.25 U/reaction did not influence the
      inhibition. The same inhibition was detected if the annealing temperature was
      changed from 48 degrees C to 57 degrees C. Pairs of EHEC primers inhibited a
      Salmonella enteritidis virulence-plasmid specific gene amplification, as well.
      Theoretical inhibiting effects were predicted by Primer Premier software but our
      observations can be sufficiently explained neither by the competitions between
      the specific and aspecific amplifications nor by the inhibition caused by
      dimerization of primers.

PMID- 9768293
TI  - Fast method to remove UV absorbing agarose gel contamination from DNA samples.
AB  - Agarose gel electrophoresis and subsequent purification of DNA bands from the
      agarose gel is a widely used molecular biological method. There are different
      methods to achieve this goal, however they have different advantages and
      disadvantages. One major problem is the presence of different contaminants in the
      final sample. We developed a method which is effective in removal of the agarose
      contaminants.

PMID- 9768294
TI  - Effect of antilymphocyte serum on bacterial translocation in mice.
AB  - Following intraperitoneally applied treatment with antilymphocyte serum (ALS) of
      immunosuppressive effect no bacterial translocation (BT) was observed in mice.
      The ALS treatment applied in combination with other immunosuppressive agents such
      as lymphotropic cytostatics as dianhydrogalactitol or chlorpromazine did not
      increase the mice's drug sensitivity to the used agents. According to our
      results, ALS can be suitable for combined application with other
      immunosuppressive agents as it can increase immunosuppression without side
      effects such as those induced by bacterial translocation.

PMID- 9768295
TI  - The incidence and characteristics of violent men in substance abuse treatment.
AB  - Linkage between marital violence and substance abuse has been noted in men
      seeking treatment for substance-use disorders. The present study examined (1) the
      incidence of family violence in men admitted into substance abuse treatment; (2)
      the psychosocial characteristics associated with marital violence; and (3) the
      comparability of violent substance abusers to their treatment cohorts. Fifty-nine
      men in substance abuse treatment involved in a significant relationship in the
      past year were assessed for substance abuse, family violence, psychosocial
      functioning, and personality attributes. Fifty-eight percent of men reported at
      least one incident of physical familial violence in the past year, while 100% of
      the men reported having engaged in psychological abuse in the past year.
      Additionally, greater violence was associated with interpersonal insensitivity,
      hostile outbursts, and poorer overall functioning independent of substance abuse.
      Finally, violent male substance abusers reported significantly more hostility,
      suspiciousness, projection of blame, and interpersonal inadequacy than did the
      less violent substance abusers. These findings suggest that, in drug-treatment
      settings, systematic objective screening for family violence is routinely called
      for.

PMID- 9768296
TI  - Social skills, expectancies, and drinking in adolescents.
AB  - Research in the field of teenage drinking behavior has shown relationships
      between both social skills and drinking and alcohol expectancies and drinking.
      The present research investigated the comparative power of both of these sets of
      variables in predicting teenage drinking behavior, as well as looking at the
      contribution of more global cognitive structures. It was hypothesised that
      adolescents with high alcohol involvement would be discriminated from those with
      low involvement on the basis of social skills, cognitive structures, and alcohol
      expectancies. Seven hundred thirty-two adolescents participated in the study.
      Results indicated that adolescent alcohol involvement was associated with social
      skills deficits, positive alcohol expectancies, and negative cognitive structures
      concerning parents and teachers. The results revealed that, although the bulk of
      the variance in drinking behavior was explained by the independent effects of
      social skills and expectancies, the interaction of the two constructs explained
      an additional and significant proportion of the variance. Implications for
      preventive and treatment programs are discussed.

PMID- 9768297
TI  - Habit control expectancy for drinking, smoking, and eating.
AB  - Habit-specific locus of control measures for drinking, smoking, and eating were
      compared to Rotter's general measure to evaluate the relationship between
      cognitive expectancy and substance use. For both smoking and eating, individuals
      who reported being addicted were significantly more external on the habit
      specific expectancy measures. Measures of use, tolerance, and risk covaried more
      closely with the habit-specific scales than with the general scale. For eating
      behavior, the habit-specific scale and the compulsive eating measure were
      different only for individuals with a history of being overweight. The habit
      specific expectancy measures were more closely related to indices of use and
      addiction than the general locus of control measure and should have greater
      utility for research and intervention.

PMID- 9768298
TI  - The role of weight concern and self-efficacy in smoking cessation and weight gain
      among smokers in a clinic-based cessation program.
AB  - Although the majority of smokers are concerned about postcessation weight gain,
      few studies have investigated the prospective relationship between weight concern
      and smoking and weight outcomes, or a mechanism by which concern is related to
      these outcomes. We investigated the prospective role of smoking-specific weight
      concern in smoking cessation and weight gain among participants in a smoking
      cessation clinic, and we hypothesized that domain-specific self-efficacy would be
      a mediator of these relationships. While weight concern did not prospectively
      predict smoking status, increased weight concern predicted weight gain at the end
      of treatment and at 3-month follow-up. Self-efficacy for preventing postcessation
      weight gain mediated this relationship; lower levels were related to a greater
      likelihood of weight gain. Weight gain was found to be associated with subsequent
      relapse among abstainers. Implications and treatment recommendations are
      discussed.

PMID- 9768299
TI  - Frequent childhood geographic relocation: its impact on drug use initiation and
      the development of alcohol and other drug-related problems among adolescents and
      young adults.
AB  - Early geographic relocation has been implicated as an important correlate of
      psychopathology, learning difficulties, and behavioural problems among child and
      adolescent populations, yet systematic studies of the potential influence of
      relocation on youthful drug use have not been conducted. This study explored the
      relationship between number of geographic moves before the age of 16 and the
      timing of onset of drug use and progression to drug-related problems. Data were
      obtained from 3,700 young adults aged 18 to 35 years participating in the 1990
      1991 Ontario Mental Health Supplement, a large random probability survey of the
      residents of the Province of Ontario, Canada. Holding constant potential
      confounding factors, results showed highly significant positive relationships
      between moving and early initiation of illicit drugs including marijuana,
      hallucinogens, crack/cocaine, and illicit use of prescribed drugs. Among
      marijuana users, moving was also associated with a hastening of time to marijuana
      related problems. Relationships between moving and measures of alcohol
      use/problems (onset of first drink, onset of any alcohol-related problem) were
      either weak or nonsignificant. Important sex differences were found, with
      statistically significant relationships between moving and early drug use
      initiation and progression occurring primarily among males. Future research is
      required to test for possible mediating mechanisms linking relocation with drug
      use as well as moderating influences. Efforts should also focus on finding out
      why drug use appears to be a more common response to relocation among boys.

PMID- 9768300
TI  - Effects of maternal cigarette smoking during pregnancy on long-term physical and
      cognitive parameters of child development.
AB  - The negative impact of maternal cigarette smoking during pregnancy on the growth
      and development of the foetus has been well documented. However, the long-term
      effects of the subsequent cognitive and physical development of the child are
      less clearly understood. This article presents a critical review of the
      literature on this topic. The review shows that the effects of prenatal exposure
      to smoking on children's physical development are mediated by a dose-response
      relationship. Although the observed effects are long term, they are small and may
      have no major functional importance. The evidence on the long-term consequences
      of intellectual function is still unclear. One reason is that very few studies
      have looked at the long-term consequences of maternal smoking on both physical
      and cognitive development. More effort is needed to investigate this important
      issue.

PMID- 9768301
TI  - Application of the transtheoretical model of behavior change for obesity in
      Mexican American women.
AB  - The prevalence, consequences, and resistance to treatment of obesity make it one
      of the most difficult psychological and medical problems in society today. The
      incidence of obesity is greater in Mexican Americans than in Caucasians. The
      purpose of this study was to apply the Transtheoretical Model of Behavior Change
      on a sample of Mexican American women in weight-loss study. Questionnaires
      assessing the stages and processes of change were shortened, translated, and
      administered to subjects. Cluster analyses were conducted to determine the stage
      of change profiles, with five distinct profiles emerging. These profiles are
      consistent with those reported in previous research on smoking, psychotherapy,
      alcoholism, and overeating. Relationships among stages, processes, and profiles
      of change were examined and found to be consistent with previous research. This
      study supports the use of the Transtheoretical Model with Mexican American women
      who were enrolled in a behaviorally oriented weight-loss program. Results of the
      study are limited owing to a small sample size; however, it does provide a
      foundation to incorporate Hispanic populations in future studies pertaining to
      stages and processes of behavior change.

PMID- 9768302
TI  - Hazelden's model of treatment and its outcome.
AB  - Although the Minnesota Model of treatment for alcohol and drug addiction is a
      common treatment approach, there are few published reports of its effectiveness.
      This study describes the Minnesota Model treatment approach as practiced at
      Hazelden, a private residential alcohol and drug abuse treatment center located
      in Center City, Minnesota (a founding program of the Minnesota Model) and
      presents recent outcome results from this program. This study includes 1,083 male
      and female clients admitted to Hazelden for treatment of a psychoactive substance
      use disorder between 1989 and 1991. The outcome study is a one group
      pretest/posttest design. Data collection occurred at admission to treatment and
      at 1-month, 6-month, and 12-month posttreatment. At 1-year follow-up, 53%
      reported that they remained abstinent during the year following treatment and an
      additional 35% had reduced their alcohol and drug use. These results are similar
      to those reported by other private treatment programs. The Minnesota Model has
      consistently yielded satisfactory outcome results, and future research needs to
      focus on the therapeutic process of this common treatment approach.

PMID- 9768303
TI  - A prototype analysis of psychological situations through the lens of alcohol
      expectancies and gender.
AB  - The psychological situation, with significant origins in cognitive and
      personality psychology, consists of the meaningful environment encountered by an
      individual at a given time. In the present study, participants generated the
      characteristics (environmental, emotional, social, and cognitive) that they found
      as characteristic of "dating," "blind dating," and "drinking with friends"
      situations. Participants also completed a brief form of the Alcohol Expectancy
      Questionnaire (Brown, Goldman, Inn, & Anderson, 1980). Results indicate that
      women were more likely to characterize "drinking with friends" with negative
      descriptors; women were also likely to have more overlap than men in their
      schemas for "dating" and "drinking with friends." Participants with stronger
      alcohol expectancies also displayed more overlap in their schemas for "dating"
      and "drinking with friends" than did those with weaker expectancies. Results are
      discussed in terms of differing drinking experiences for men and women, and on
      the relationship between situational cues and expectancies.

PMID- 9768304
TI  - Regret, substance abuse, and readiness to change in a dually diagnosed sample.
AB  - The transtheoretical stages of change model posits that increased readiness to
      change is associated with greater awareness of the negative consequences of
      substance use. Experiencing regrets implies a greater awareness of these
      consequences. Eighty dually diagnosed patients completed a 22-item Measure of
      Substance-Related Regret (MSR) that assessed the intensity, type, idiographic
      importance of, and emotions associated with regrets related to substance use and
      the Brief Readiness to Change Questionnaire. The MSR yielded a global measure of
      regret that accounted for statistically significant amounts of variance in total
      readiness-to-change scores (R2 = .30). Global scores also predicted
      precontemplation and contemplation stage scores, whereas total fear scores
      associated with regrets predicted action scores. Regret seems to play a complex
      yet important role in the decision to change substance abuse.

PMID- 9768305
TI  - Predictors of participation in a smoking cessation intervention group among low
      income women.
AB  - The predictors of participation in a smoking cessation group among low-income
      women were examined. Fifty smokers were recruited from a Midwestern community
      primary care setting serving an uninsured, underinsured, and Medicaid population.
      Participants completed a questionnaire before the intervention, and eleven women
      chose to participate in the 6-week sessions. There were few differences between
      the control group (nonparticipants) and the intervention group. The intervention
      group had significantly higher intention-to-quit scores. Logistic regression
      analysis was used to predict group membership with age, self-efficacy, optimism,
      social support, nicotine dependence, intention-to-quit, and other smokers in the
      home as the predictor variables. The only two significant predictors of
      participation in the cessation intervention were self-efficacy and intention-to
      quit smoking. The higher the intention-to-quit score and the lower the self
      efficacy score (the belief that one can be successful in not smoking); the more
      likely these women were to participate in the group intervention. Results are
      discussed in terms of their clinical relevance as well as future research in the
      area.

PMID- 9768306
TI  - Predicting drug use: application of behavioral theories of choice.
AB  - The current study sought to test the utility of Herrnstein's (1970) matching law
      in predicting drug use occurring in the natural environment. Participants were
      206 college students. Behavioral allocation was measured across two concurrently
      available sets of activities: those engaged in while using or under the influence
      of drugs and/or alcohol (drug related) and those engaged in when drug free.
      Results from regression analyses indicate that predictions of drug use are
      improved with the addition of reinforcement received from drug-free activities,
      which enters the model with a negative coefficient value. The addition of a
      reinforcement ratio, based on matching law equations, also accounted for unique
      variance. Results demonstrate the utility of applying behavioral theories of
      choice to drug use and highlight the importance of viewing behaviors within their
      broader environmental context.

PMID- 9768307
TI  - Creativity of undergraduates with and without family history of alcohol and other
      drug problems.
AB  - Noble, Runco, and Ozkaragoz (1993) provided evidence that alcoholics' children
      differ negatively from recovering alcoholics' and nonalcoholics' children in
      terms of personality characteristics related to creativity. They also found that
      divergent thinking test scores among the three groups of children are similar,
      yet the possibility exists that offspring compensate for the personality deficits
      and maintain productively creative lives in spite of the negative influence of
      parental substance use. This study investigated the impact of parental substance
      abuse problems on 163 undergraduates' creative achievement. With current alcohol
      consumption as a covariate, analysis of covariance results suggest that parental
      alcohol and drug problems do not have an appreciable effect on students' creative
      achievement, although marginally significant interaction of gender and family
      history provides limited evidence that gender may influence the impact of
      parental substance abuse on creativity. Because the true effects of parental
      substance abuse may not be felt for several years, future research should
      investigate these issues with older offspring.

PMID- 9768308
TI  - Psychoanalysis and the model of homosexuality as psychopathology: a historical
      overview.

PMID- 9768309
TI  - Elma Laurvik, Ferenczi's stepdaughter.

PMID- 9768310
TI  - Horney, Zen, and the real self.

PMID- 9768311
TI  - Self-esteem: the past of an illusion.

PMID- 9768312
TI  - Induced recall of film music: an overlooked mirror of transference
      countertransference interactions.

PMID- 9768313
TI  - Lacan's theory of self and the story of the last cookie.

PMID- 9768314
TI  - Effect of sinus surgery on visual disturbance caused by spheno-ethmoid mucoceles.
AB  - Fifteen patients suffering from visual disturbance of varying degrees caused by a
      mucocele of the posterior ethmoid and/or sphenoid sinuses underwent
      marsupialization of a mucocele into the nasal cavity. Five of the eight patients
      with severe visual loss worse than 20/200 showed recovery of measurable vision.
      Two of these five were operated on within 24 hours after the onset of visual loss
      and showed marked recovery to 20/25 and 20/15. The other seven patients who had
      relatively mild visual disturbance experienced improvement of visual acuity or
      remission of subjective complaints such as blurred vision post-operatively.
      During operation partial bony defect was found in the optic canal in 12 patients
      and in the skull base in 12 patients. A good understanding of this disease by
      ophthalmologists and otolaryngologists is essential for early diagnosis and
      prompt surgical treatment to avoid permanent visual dysfunction and operative
      sequelae.

PMID- 9768315
TI  - Myospherulosis of the upper eyelid as a complication of endoscopic sinus surgery.
AB  - Myospherulosis is a chronic inflammatory reaction to the mixture of red blood
      cells and petroleum based ointments. A literature review does not reveal any
      cases involving ophthalmic manifestations. We present the first reported case of
      a patient experiencing recurrent eyelid inflammation from myospherulosis after
      endoscopic sinus surgery. The pathophysiology and management of myospherulosis
      are discussed.

PMID- 9768316
TI  - Combined endoscopic intranasal and external frontal sinusotomy.
AB  - We review our experience treating patients with medically refractory frontal
      sinusitis that could not be relieved with endoscopic intranasal surgery alone.
      Fourteen combined external and intranasal endoscopic frontal sinusotomies were
      performed on a consecutive sample of 11 patients presenting over a 38-month
      period of study. Postoperative results were classified as cured, improved,
      unchanged, or worse, based on patient symptoms and physical findings. At a mean
      postoperative follow-up of 19 months (range 4-36), 100% of these patients had
      benefited from this technique (7 cured, 4 improved, 0 unchanged, 0 worse). There
      were no major complications and natural sinus physiology was preserved. We
      conclude that a combined external and endoscopic intranasal frontal sinusotomy is
      an effective alternative to frontal sinus obliteration.

PMID- 9768317
TI  - Intranasal anatomic variations in pediatric sinusitis.

PMID- 9768318
TI  - Recirculation of mucus as a cause of persistent sinusitis.
AB  - Recirculation of mucus between adjacent openings into the maxillary antrum is a
      relatively common cause of persistent sinusitis in either the pre- or
      postsurgical patient. It is particularly common after FESS when the new middle
      meatal antrostomy has been sited too far posteriorly behind an existing natural
      maxillary ostium. The condition is easily diagnosed with the nasal endoscope and
      the surgical remedy of joining the separate openings into one larger antrostomy
      is readily carried out under local anesthesia in the rhinologist's office.

PMID- 9768319
TI  - A comparison of two methods for determining nasal irritant sensitivity.
AB  - Nasal irritation and irritant-induced reflexes (rhinorrhea and congestion) are
      prominent symptoms associated with indoor and ambient air pollution, and marked
      heterogeneity in individual sensitivity has been suggested. Nevertheless, there
      is currently no generally accepted functional index of nasal irritant sensitivity
      available for clinical use. To address this issue, we compared two objective
      measures of nasal irritant sensitivity: a CO2 detection task, and CO2-induced
      transient disruption of respiratory pattern (pulsed CO2 acting as an odorless
      irritant). Using a respiratory flow thermocouple to produce a continuous
      recording of respiratory pattern, we challenged 20 normal adult volunteers (13
      males and 7 females, average age 39.4 years) with brief (approximately 3 second)
      pulses of the odorless irritant carbon dioxide. Increasing levels of CO2 (10-70%,
      vol/vol), paired with filtered air in random order, were presented unilaterally
      by nasal cannula of fixed geometry, synchronized with the inspiratory phase of
      the respiratory cycle. All subjects yielded CO2 detection thresholds, whereas
      within the constraints of the testing method (subjective irritation rating < or =
      "very strong"), only 13 of 20 subjects (65%) exhibited transient disruption of
      their breathing pattern. Further, although decreased respiratory volume
      (indirectly measured) appeared to be a common feature, several distinct patterns
      of respiratory alteration were observed, rendering objective scoring more
      difficult. Finally, some subjects showed CO2-induced respiratory disruption
      intermittently from trial to trial, implying that rapid adaptation occurs.
      Determination of the CO2 detection threshold therefore appears to be the more
      objective and consistently applicable endpoint for determining individual nasal
      irritant sensitivity.

PMID- 9768320
TI  - Acoustic rhinometric assessment of the nasal valve.
AB  - The aims of this study are to assess nasal valve cross-sectional areas in healthy
      noses and in patients with nasal obstruction after rhinoplasty and to evaluate
      the effect of an external nasal dilator on both healthy and obstructive nasal
      valves. Subjects consisted of (i) volunteers with no nasal symptoms, nasal
      cavities unremarkable to rhinoscopy and normal nasal resistance and (ii) patients
      referred to our clinic complaining of postrhinoplasty nasal obstruction. All
      subjects were tested before and after topical decongestion of the nasal mucosa
      and with an external nasal dilator. In 79 untreated healthy nasal cavities the
      nasal valve area showed two constrictions: the proximal constriction averaged
      0.78 cm2 cross-section and was situated 1.18 cm from the nostril, the distal
      constriction averaged 0.70 cm2 cross-section at 2.86 cm from the nostril. Mucosal
      decongestion increased cross-sectional area of the distal constriction
      significantly (p < 0.0001) but not the proximal. External dilation increased
      cross-sectional area of both constrictions significantly (p < 0.0001). In 26 post
      rhinoplasty obstructed nasal cavities, only a single constriction was detected,
      averaging 0.34 cm2 cross-section at 2.55 cm from the nostril and 0.4 cm2 at 2.46
      cm from the nostril, before and after mucosal decongestion respectively. External
      dilation increased the minimum cross-sectional area to 0.64 cm2 in these nasal
      cavities (p < 0.0001). We conclude that the nasal valve area in patients with
      postrhinoplasty nasal obstruction is significantly smaller than in healthy nasal
      cavities as shown by acoustic rhinometry. Acoustic rhinometry objectively
      determines the structural and mucovascular components of the nasal valve area and
      external dilation is an effective therapeutical approach in the management of
      nasal valve obstruction.

PMID- 9768321
TI  - Magnetic resonance cisternography and thin coronal computerized tomography in the
      evaluation of cerebrospinal fluid rhinorrhea.
AB  - In recent years cerebrospinal fluid (CSF) rhinorrhea has been managed
      successfully with transnasal endoscopic techniques. The most important and often
      most difficult step is the precise localization of the fistula. Computerized
      tomographic and radionuclide cisternography are two commonly used techniques for
      preoperative identification of the CSF fistula when it cannot be seen clearly
      with nasal endoscopy. Each of these requires a lumbar puncture, and the
      intrathecal placement of contrast material has been associated with transient
      neurotoxicities. Magnetic resonance cisternography (MRC) is a noncontrast study
      that does not require a lumbar puncture and has been used recently in the
      diagnosis of spontaneous and traumatic CSF leaks. Magnetic resonance
      cisternography utilizes a fast spin-echo sequence with fat suppression and video
      image reversal that highlights CSF. This allows precise localization of the
      fistula in both coronal and sagittal planes. Thin section coronal computed
      tomography (TCCT) is another noninvasive technique that can be helpful in
      localizing CSF leaks. The technique of MRC and TCCT and the results of 16 CSF
      leaks in 15 patients are reported. There was good correlation between MRC, TCCT,
      and intraoperative findings. Magnetic resonance cisternography and thin coronal
      computerized tomography appear to be accurate and complementary, noninvasive
      radiographic studies that should be considered in the evaluation CSF rhinorrhea.

PMID- 9768322
TI  - Objective assessment of the breathe-right device during exercise in adult males.
AB  - In order to improve nasal breathing during competition, many athletes recently
      have been wearing a spring-loaded, external nasal dilator referred to as the
      Breathe-Right device (BRD). Although there are many subjective claims that this
      device improves breathing during exercise, there are currently no controlled
      studies documenting its efficacy. To determine objectively whether the device
      improves the nasal airway, 20 subjects (10 Caucasian and 10 African-American)
      were studied during rest and after 15 minutes of exercise using anterior
      rhinomanometry and acoustic rhinometry to measure changes in airway resistance
      and minimal cross-sectional area, respectively. We found that the BRD exerts its
      main effect in the region of the nasal valve improving the airway an overall 21%
      in our group of subjects. This anatomic improvement in nasal airway resulted in
      an overall 27% reduction in nasal resistance in the Caucasian group. However, in
      the African-American group, a wider range of resistance changes was observed with
      application of the BRD with significant improvement in nasal resistance in some
      subjects but paradoxical worsening in others. In the African-American group as a
      whole, no significant change in nasal resistance occurred with application of the
      BRD. These measured differences are likely due to variations in nasal anatomy
      that exist not only between races but also between individuals within a given
      race. In addition, this study confirms the well known decongestant effects of
      exercise providing anatomic data with acoustic rhinometry not previously
      documented in the literature. Overall improvement in nasal airway seen with
      application of the BRD occurred independent of these exercise-related
      decongestant effects.

PMID- 9768323
TI  - Effects of the Breathe Right nasal strips on nasal ventilation.
AB  - The Breathe Right nasal strips are more and more commonly used, mainly by
      athletes, who hope to enhance their physical performance in competition and
      training. The effect of the device in such situations is uncertain and perhaps
      somewhat controversial. To investigate the effects of the nasal strips on nasal
      ventilation, 20 caucasian individuals were objectively assessed using anterior
      rhinomanometry and acoustic rhinometry. The results showed a significant increase
      in all subjects of transnasal airflow and in the average cross-sectional area of
      the nasal cavity that quantifies objectively the subjective impression of
      improved nasal breathing. In such patients where an improvement in nasal
      ventilation is desired, the use of the Breathe Right nasal strips seems to offer
      a beneficial treatment.

PMID- 9768325
TI  - DNA diagnosis of cystic fibrosis.

PMID- 9768324
TI  - Insulin resistance.

PMID- 9768326
TI  - Multiplex genotyping for cystic fibrosis from filter paper blood spots.
AB  - Cystic fibrosis is a common disease of the Caucasian population and is associated
      with significant early mortality. We present a simple and rapid method for cystic
      fibrosis genotyping from filter paper blood spots, using a currently available
      commercial genotyping kit. Using multiplex technology, genotype information on
      the four most common UK mutations can easily be obtained within a single working
      day. Used in conjunction with current immunoreactive typsinogen screening
      protocols, blood spot genotyping offers a method of hastening the diagnosis, and
      thus treatment, of cystic fibrosis.

PMID- 9768327
TI  - Plasma antioxidants: evidence for a protective role against reactive oxygen
      species following cardiac surgery.
AB  - Total plasma antioxidant status (TPAS), lipid peroxide concentration (LPX) and
      cardiac troponin T (cTnT) were measured in 24 patients undergoing coronary artery
      bypass grafting (CABG) with cardiopulmonary bypass (CPB). Samples were obtained
      preoperatively and at 1.5 h, 6 h, 24 h and 72 h after CPB. The absolute TPAS
      values were significantly lower at 1.5 h, 6 h, 24 h and 72 h after CPB than were
      preoperative values (P < 0.05). The LPX concentration was significantly elevated
      at 1.5 h after CPB (P < 0.05). Cardiac troponin T concentrations were
      significantly elevated at all time points postoperatively (P < 0.05).
      Preoperative TPAS values were significantly correlated with the magnitude of fall
      in TPAS at 1.5 h (P < 0.05). The greater the fall in TPAS between 0 and 1.5 h,
      the less LPX was formed between 0 and 1.5 h. The LPX at 1.5 h displayed a
      significant correlation with cTnT release from myocardial myocytes (P < 0.05).
      These data provide evidence for the first time that the consumption of
      antioxidants during CABG surgery with CPB protects against the production of
      reactive oxygen species and subsequent myocyte necrosis. Furthermore, the
      availability of protective antioxidants is dependent upon preoperative TPAS.

PMID- 9768328
TI  - Multianalyte serum analysis using mid-infrared spectroscopy.
AB  - This study assesses the potential for using mid-infrared (mid-IR) spectroscopy of
      dried serum films as the basis for the simultaneous quantitation of eight serum
      analytes: total protein, albumin, triglycerides, cholesterol, glucose, urea,
      creatinine and uric acid. Infrared transmission spectra were acquired for 300
      serum samples, each analysed independently using accepted reference clinical
      chemical methods. Quantitation methods were based upon the infrared spectra and
      reference analyses for 200 specimens, and the models validated using the
      remaining 100 samples. Standard errors in the IR-predicted analyte levels (Sy/x)
      were 2.8 g/L (total protein), 2.2 g/L (albumin), 0.23 mmol/L (triglycerides),
      0.28 mmol/L (cholesterol), 0.41 mmol/L (glucose) and 1.1 mmol/L for urea, with
      correlation coefficients (IR vs reference analyses) of 0.95 or better. The IR
      method emerged to be less suited for creatinine (Sy/x = mumol/L) and uric acid
      (Sy/x = 140 mumol/L) due to the relatively low concentrations typical of these
      analytes.

PMID- 9768329
TI  - Determination of serum physiological concentration of methylmalonic acid by gas
      chromatography-mass spectrometry with selected ion monitoring.
AB  - We developed a sensitive assay for the rapid determination of serum methylmalonic
      acid concentration using capillary gas chromatography-mass spectrometry (GC/MS)
      with selected ion monitoring and a simple solid-phase extraction. The assay was
      linear up to 10,000 nmol/L and had a detection limit < 50 nmol/L, average
      recovery of 98% and between-day coefficient of variation at concentrations of 570
      and 2206 nmol/L of 7.7% and 5.4%, respectively (n = 25). Comparison with another
      validated GC/MS method using sera with a wide range of methylmalonic acid
      concentrations (94-2020 nmol/L) revealed a slope and intercept of 0.97 and 17
      nmol/L, respectively (n = 38). Methylmalonic acid concentrations determined by
      this assay in a group of apparently healthy individuals ranged from 64-331 nmol/L
      (n = 81). We conclude that the method is ideally suited for the determination of
      methylmalonic acid at physiological concentrations in both clinical and research
      laboratories.

PMID- 9768331
TI  - Distribution and expression of adrenomedullin in human gastrointestinal tissue.
AB  - Adrenomedullin (AM) is a biologically active peptide recently isolated from
      phaeochromocytoma. We report here the distribution and characterization of
      immunoreactive AM and gene expression of AM in human gastrointestinal tissue.
      Using a sensitive radioimmunoassay system for the peptide, immunoreactive human
      AM was detected in the stomach, duodenum, jejunum, ileum and colon. The AM
      concentration of these tissues was about 0.4-0.8 pmol/g wet tissue. Reverse phase
      and gel filtration high-performance liquid chromatographies showed that most of
      the immunoreactive AM in stomach and jejunum was identical to authentic human AM.
      By northern blot analysis, human AM mRNA was found to be expressed ubiquitously
      in the human gastrointestinal tissues. Furthermore, an immunohistochemical study
      revealed that immunoreactive AM cells were present in the gastrointestinal
      glands. These results suggest that AM may play some role as a gastrointestinal
      hormone.

PMID- 9768330
TI  - Effects of sex steroid hormones on corticosteroid-binding globulin gene
      expression in human endometrial cancer cell line Ishikawa.
AB  - The effect of progestins on intracellular corticosteroid-binding globulin (CBG)
      mRNA expression in an endometrial cancer cell line (Ishikawa) was examined in an
      attempt to understand the biological effects of high-dose progestins in the
      treatment of well-differentiated uterine endometrial cancers. Oestradiol-17 beta
      (E2) significantly increased CBG mRNA expression in a dose-dependent manner,
      while a high dose of progesterone with or without E2 suppressed it significantly.
      Furthermore, a high dose of progesterone or medroxyprogesterone acetate (MPA)
      suppressed CBG mRNA expression to a greater degree than did chlormadinone acetate
      or 17 alpha-hydroxyprogesterone caproate with or without E2. These findings
      suggest that the effects of high-dose progestins on cancer cells may be mediated
      via suppression of intracellular CBG.

PMID- 9768332
TI  - Sensitive enzyme immunoassay for anti-beta-lactoglobulin IgG in serum.
AB  - A sensitive enzyme immunoassay for anti-beta-lactoglobulin immunoglobulin G (IgG)
      in serum is described. Serum containing anti-beta-lactoglobulin IgG was reacted
      simultaneously with 2,4-dinitrophenyl-bovine serum albumin-beta-lactoglobulin
      conjugate and beta-lactoglobulin-peroxidase conjugate. The complex formed from
      the three components was trapped onto polystyrene balls coated with anti-2,4
      dinitrophenyl group IgG, eluted with epsilon N-2,4-dinitrophenyl-L-lysine and
      transferred to polystyrene balls coated with anti-human IgG.gamma-chain IgG.
      Bound peroxidase activity was determined by fluorometry. This enzyme immunoassay
      was 100- to 1000-fold more sensitive and more reliable than the enzyme-linked
      immunosorbent assay (ELISA). Anti-beta-lactoglobulin IgG was detected in 91% of
      healthy subjects using this method.

PMID- 9768333
TI  - Evolution of an inhibin A ELISA method: implications for Down's syndrome
      screening.
AB  - The development of a sensitive and specific enzyme-linked immunoassay (ELISA) for
      inhibin A stimulated the observation that inhibin A was a useful prenatal marker
      of Down's syndrome. Modifications of that ELISA, in terms of preassay sample
      treatment, detection methods and standard preparation, were subsequently
      introduced to improve assay performance and reduce costs. These modified formats
      have been validated and reported. We describe the modifications in detail,
      explaining the rationale for each, and report the results of a study directly
      comparing the various ELISA formats in terms of assay performance when applied to
      clinical samples and ability to differentiate between normal and Down's syndrome
      pregnancies. A format involving sample pretreatment with sodium dodecylsulphate
      at 100 degrees C was found to give better assay performance and a modest
      improvement in discrimination between Down's syndrome samples and controls, and
      we recommend this format for use by other investigators.

PMID- 9768335
TI  - Evaluation of a latex-enhanced immunoturbidimetric assay for measuring low
      concentrations of C-reactive protein.

PMID- 9768334
TI  - Automated fluorimetric determination of cellular cholesterol.
AB  - We developed a completely automated fluorimetric method for the determination of
      cellular cholesterol, consisting of enzymatic hydrolysis of cholesteryl ester to
      free cholesterol and enzymatic oxidation of free cholesterol in the presence of
      an indicator substrate to produce a fluorescent product. For control preparations
      of monocytes, the mean detection limit was 2.57 mumol/5 x 10(5) cells and the
      mean within-batch coefficients of variation were 9.30, 6.00 and 3.73% at mean
      cholesterol concentrations of 1.94, 9.05 and 12.49 mumol/5 x 10(5) cells,
      respectively. The results correlated well with those obtained by gas-liquid
      chromatography.

PMID- 9768336
TI  - Haemochromatosis case detection by genetic testing: a new era.

PMID- 9768337
TI  - Thrombocytopenia and giant platelets without major haemorrhagic complications in
      a pregnant patient.

PMID- 9768338
TI  - Wilson's disease: gall stone copper following liver transplantation.

PMID- 9768339
TI  - CSF spectrophotometry and subarachnoid haemorrhage.

PMID- 9768340
TI  - What is the role of CSF spectrophotometry in the diagnosis of subarachnoid
      haemorrhage?

PMID- 9768341
TI  - Interference in pancreolauryl test.

PMID- 9768342
TI  - Addition of further blood to the Boehringer Advantage blood glucose meter.

PMID- 9768343
TI  - The role of cytokines in the normal and neoplastic pituitary.

PMID- 9768344
TI  - The surgical treatment of lung metastases: an update.

PMID- 9768345
TI  - Use of L-asparaginase in childhood ALL.
AB  - Owing to the high efficacy of L-asparaginase in the treatment of acute lymphatic
      leukaemia the enzyme was introduced into the chemotherapy schedules for remission
      induction of this disease shortly after results of large-scale clinical trials
      had become available. Since asparaginase monotherapy was associated with a high
      response rate but short remission duration, the enzyme is currently employed
      within the framework of combination chemotherapy schedules which achieve
      treatment response in about 90% and long-term remissions in the majority of
      patients. Recently initiated clinical trials have still confirmed the eminent
      value of asparaginase in the combination chemotherapy of acute lymphatic
      leukaemia and of some subtypes of non-Hodgkin lymphoma, and its important role as
      an essential component of multimodal treatment protocols. Despite the unique
      mechanism of action of this cytotoxic substance which shows relative selectivity
      with regard to the metabolism of malignant cells, some patients experience toxic
      effects during asparaginase therapy. Immunological reactions toward the foreign
      protein include enzyme inactivation without any clinical manifestations as well
      as anaphylactic shock. Severe functional disorders of organ systems result from
      the impaired homeostasis of the amino acids asparagine and glutamine. The changes
      affecting the proteins of the coagulation system have considerable clinical
      impact as they may induce bleeding as well as thromboembolic events and may be
      associated with life-threatening complications when the central nervous system is
      involved. Risk factors predisposing to thromboembolic complications are
      hereditary resistance against activated protein C and any other hereditary
      thrombophilia. Other organ systems potentially affected by relevant functional
      disorders are the central nervous system, the liver, and the pancreas, with
      patients who have a history of pancreatic disorders carrying an especially high
      risk of developing pancreatitis. Studies on the mechanisms of action and the
      occurrence of resistance phenomena have shown that a treatment response may only
      be expected if the malignant cells are unable to increase their asparagine
      synthetase activity to an extent providing enough asparagine to the cell; one may
      thus conclude that the enzyme-induced asparagine depletion of the serum
      constitutes the decisive cytotoxic mechanism. Independent of the asparagine
      depletion related cytotoxicity however, there are other mechanisms of clinical
      relevance like induction of apoptosis. Besides this, further influences on signal
      transduction cannot be excluded. Only few publications have dealt with the
      question of minimum trough activities to be ensured before each subsequent
      asparaginase dose in order to maintain uninterrupted asparagine depletion under
      treatment, and answers to this problem are not definitive. Clinical studies using
      enzymes from E. coli strains indicate that a trough activity of 100 U/l will
      suffice for complete asparagine depletion of the fluid body compartments with the
      preparations studied. These findings have been transferred to enzymes from other
      E. coli strains as well as those isolated from Erwinia chrysanthemi and to the
      PEG-conjugated E. coli asparaginases. It might be desirable to countercheck the
      results for confirmation or correction. The dosage and administration schedule of
      the various enzyme preparations required for complete asparagine depletion over a
      period of time have been insufficiently defined. While pharmacokinetic studies
      showed clinically relevant differences in biological activity and activity half
      lives for enzymes from different biological sources, the findings of recently
      published clinical trials indicate that the therapeutic efficacy is affected when
      different asparaginase preparations are given by identical therapy schedules.
      (ABSTRACT TRUNCATED)

PMID- 9768346
TI  - Diet and breast cancer: an epidemiologist's perspective.

PMID- 9768347
TI  - Fertility and pregnancy after adjuvant chemotherapy for breast cancer.

PMID- 9768348
TI  - EBV genes and B cell proliferation.

PMID- 9768349
TI  - Going for the GAP.

PMID- 9768350
TI  - Single calponin homology domains are not actin-binding domains.

PMID- 9768351
TI  - Hox genes: from master genes to micromanagers.
AB  - We still have little idea how the differential expression of one 'master' gene
      can control the morphology of complex structures, but recent studies suggest that
      the Drosophila Hox gene Ultrabithorax micromanages segment development by
      manipulating a large number of different targets at many developmental stages.

PMID- 9768352
TI  - Bone remodelling: a signalling system for osteoclast regulation.
AB  - Two physiological regulators of osteoclast maturation have recently been
      identified: the secreted protein osteoprotegerin and the cell-surface ligand to
      which it binds. These proteins are likely to play an important part in the
      control of bone resorption, but are also likely to have important roles in other
      tissues.

PMID- 9768353
TI  - Transcriptional control: repression by local chromatin modification.
AB  - It is becoming increasingly clear that chromatin modification plays a fundamental
      part in transcriptional control. Recent studies provide new insights into how
      transcriptional repressors, in addition to blocking activators, may recruit
      repression complexes that include chromatin modification factors.

PMID- 9768354
TI  - Size control: cell proliferation does not equal growth.
AB  - Division subdivides mass without increasing it. So one should not expect that an
      increase in cell division would make an organism bigger. Both classic and recent
      experiments confirm this simple rationale: altering proliferation produces
      normally sized body structures with either especially small or exceptionally
      large cells.

PMID- 9768355
TI  - Flowering time: from photoperiodism to florigen.
AB  - An Arabidopsis blue-light receptor, Cry2, has been found to play a critical role
      in the photoperiodic control of flowering time; and genes have been identified
      that may control the production of a transmissible flower-inducing signal, which
      may turn out to be the long-elusive putative flowering hormone 'florigen'.

PMID- 9768356
TI  - Apoptosis: getting rid of the bodies.
AB  - Cells that die by apoptosis need to be removed before lysis to preserve tissue
      integrity and function. Recent studies have identified components of the uptake
      machinery used by phagocytes, but much remains to be learnt, particularly about
      the recognition mechanisms and their coupling to the uptake machinery.

PMID- 9768357
TI  - Gene therapy: repairing haemoglobin disorders with ribozymes.
AB  - A ribozyme-mediated approach has made it possible to replace the region in beta
      globin mRNA containing the sickle-cell-anaemia mutation with a gamma-globin
      encoding sequence. This is an interesting new way of correcting monogenic
      disease, but there are major problems to overcome before it could be applied in
      the clinic.

PMID- 9768358
TI  - Multiple functions of the EGF receptor in Drosophila eye development.
AB  - BACKGROUND: During animal development, cells need to make spatially and
      temporally regulated fate decisions. These decisions are largely controlled by
      intercellular signalling, often through receptor tyrosine kinases. One of these,
      the epidermal growth factor receptor (EGFR), regulates multiple cell fate
      decisions. Its importance in the recruitment of photoreceptors in the developing
      fly eye, a useful model for neural development, has already been reported. Other
      EGFR functions in the eye have not been characterised. RESULTS: We have examined
      the consequences of removing or activating the EGFR at different stages of eye
      development. The earliest stages of assembly occurred normally within EGFR-
      clones--the morphogenetic furrow was unimpeded and the R8 photoreceptor was
      specified. All subsequent photoreceptor recruitment was blocked. EGFR- clones had
      a characteristic shape indicating that they had undergone substantial cell death
      posterior to the furrow, where the differentiation program is normally activated;
      consistent with this, excess apoptosis was detected. We found that the receptor
      also regulates cell proliferation in the disc, has an early function at the disc
      margin (where the morphogenetic furrow initiates) and contributes to the
      regulation of spacing of the R8 precursors. Finally, we found that activation of
      the receptor is sufficient to trigger non-R8 photoreceptor development, even in
      cells in front of the furrow or in the absence of the proneural gene atonal.
      CONCLUSION: At least five distinct functions of EGFR signalling need to be
      integrated during fly eye development. These include roles in cell proliferation,
      survival and differentiation.

PMID- 9768359
TI  - Nuclear export of the stress-activated protein kinase p38 mediated by its
      substrate MAPKAP kinase-2.
AB  - BACKGROUND: Mitogen-activated protein (MAP) kinases (or extracellular signal
      regulated kinases; Erks) and stress-activated protein (SAP) kinases mediate
      cellular responses to a wide variety of signals. In the Erk MAP kinase pathway,
      activation of MAP kinases takes place in the cytoplasm and the activated enzyme
      moves to the nucleus. This translocation to the nucleus is essential to MAP
      kinase signalling because it enables the kinase to phosphorylate transcription
      factors. Whether components of the pathway mediated by the SAP kinase p38 change
      their cellular location on activation is not clear; we have therefore studied the
      cellular localisation of components of this pathway before and after stimulation.
      RESULTS: The p38 SAP kinase substrate MAP-kinase-activated protein kinase-2
      (MAPKAP kinase-2) contains a putative nuclear localisation signal which we show
      is functional and required for activation by a variety of stimuli. Following
      phosphorylation of MAPKAP kinase-2, nuclear p38 was exported to the cytoplasm in
      a complex with MAPKAP kinase-2. Export of MAPKAP kinase-2 required
      phosphorylation by p38 but did not appear to require the kinase activity of
      MAPKAP kinase-2. The p38 activators MKK3 and MKK6 were present in both the
      nucleus and the cytoplasm, consistent with a role in activating p38 in the
      nucleus. CONCLUSIONS: In the p38 SAP kinase pathway, MAPKAP kinase-2 serves both
      as an effector of p38 by phosphorylating substrates and as a determinant of
      cellular localisation of p38. Nuclear export of p38 and MAPKAP kinase-2 may
      permit them to phosphorylate substrates in the cytoplasm.

PMID- 9768361
TI  - Regulation of protein kinase C zeta by PI 3-kinase and PDK-1.
AB  - BACKGROUND: Protein kinase C zeta (PKC zeta) is a member of the PKC family of
      enzymes and is involved in a wide range of physiological processes including
      mitogenesis, protein synthesis, cell survival and transcriptional regulation. PKC
      zeta has received considerable attention recently as a target of phosphoinositide
      3-kinase (PI 3-kinase), although the mechanism of PKC zeta activation is, as yet,
      unknown. Recent reports have also shown that the phosphoinositide-dependent
      protein kinase-1 (PDK-1), which binds with high affinity to the PI 3-kinase lipid
      product phosphatidylinositol-3,4,5-trisphosphate (Ptdins-3,4,5-P3),
      phosphorylates and potently activates two other PI 3-kinase targets, the protein
      kinases Akt/PKB and p70S6K. We therefore investigated whether PDK-1 is the kinase
      that activates PKC zeta. RESULTS: In vivo, PI 3-kinase is both necessary and
      sufficient to activate PKC zeta. PDK-1 phosphorylates and activates PKC zeta in
      vivo, and we have shown that this is due to phosphorylation of threonine 410 in
      the PKC zeta activation loop. In vitro, PDK-1 phosphorylates and activates PKC
      zeta in a Ptdins-3,4,5-P3-enhanced manner. PKC zeta and PDK-1 are associated in
      vivo, and membrane targeting of PKC zeta renders it constitutively active in
      cells. CONCLUSIONS: Our results have identified PDK-1 as the kinase that
      phosphorylates and activates PKC zeta in the PI 3-kinase signaling pathway. This
      phosphorylation and activation of PKC zeta by PDK-1 is enhanced in the presence
      of Ptdins-3,4-5-P3. Consistent with the notion that PKCs are enzymes that are
      regulated at the plasma membrane, a membrane-targeted PKC zeta is constitutively
      active in the absence of agonist stimulation. The association between PKC zeta
      and PDK-1 reveals extensive cross-talk between enzymes in the PI 3-kinase
      signaling pathway.

PMID- 9768360
TI  - Sonic hedgehog signaling is essential for hair development.
AB  - BACKGROUND: The skin is responsible for forming a variety of epidermal structures
      that differ amongst vertebrates. In each case the specific structure (for example
      scale, feather or hair) arises from an epidermal placode as a result of
      epithelial-mesenchymal interactions with the underlying dermal mesenchyme.
      Expression of members of the Wnt, Hedgehog and bone morphogenetic protein
      families (Wnt10b, Sonic hedgehog (Shh) and Bmp2/Bmp4, respectively) in the
      epidermis correlates with the initiation of hair follicle formation. Further,
      their expression continues into either the epidermally derived hair matrix which
      forms the hair itself, or the dermal papilla which is responsible for induction
      of the hair matrix. To address the role of Shh in the hair follicle, we have
      examined Shh null mutant mice. RESULTS: We found that follicle development in the
      Shh mutant embryo arrested after the initial epidermal-dermal interactions that
      lead to the formation of a dermal papilla anlage and ingrowth of the epidermis.
      Wnt10b, Bmp2 and Bmp4 continued to be expressed at this time, however. When
      grafted to nude mice (which lack T cells), Shh mutant skin gave rise to large
      abnormal follicles containing a small dermal papilla. Although these follicles
      showed high rates of proliferation and some differentiation of hair matrix cells
      into hair-shaft-like material, no hair was formed. CONCLUSIONS: Shh signaling is
      not required for initiating hair follicle development. Shh signaling is
      essential, however, for controlling ingrowth and morphogenesis of the hair
      follicle.

PMID- 9768362
TI  - The Antirrhinum ERG gene encodes a protein related to bacterial small GTPases and
      is required for embryonic viability.
AB  - Small GTPases have diverse roles in animals and yeast, including signal
      transduction, regulation of secretion, organisation of the cytoskeleton, and
      control of cell division. Similar GTPases have also been found in bacteria, such
      as the Escherichia coli GTPase ERA, which is involved in regulating metabolism
      and cell division [1,2]. Many small GTPases have been cloned from plants but
      their functional analysis has largely been limited to complementation of
      mutations in corresponding yeast genes, and antisense experiments which have
      implicated these proteins in processes such as root nodulation [3,4]. No
      mutations in plant GTPases have been reported, and thus their true importance in
      plant growth and development is unknown. Here we report the isolation of a gene
      from Antirrhinum majus encoding a protein from an entirely novel class of
      eukaryotic GTPases showing strongest similarity to the prokaryotic protein ERA.
      We have named this gene ERG (for ERA-related GTPase). The ERG gene is expressed
      in dividing or metabolically active cells. We generated a deletion allele of ERG
      by site-selected transposon mutagenesis and have shown that seeds containing
      embryos and endosperm homozygous for this deletion arrest soon after
      fertilisation. We conclude that ERG has a crucial role in plant growth and
      development, possibly by influencing mitochondrial division.

PMID- 9768363
TI  - Sonic hedgehog regulates branching morphogenesis in the mammalian lung.
AB  - The mammalian lung, like many other organs, develops by branching morphogenesis
      of an epithelium [1]. Development initiates with evagination of two ventral buds
      of foregut endoderm into the underlying splanchnic mesoderm. As the buds extend,
      they send out lateral branches at precise, invariant positions, establishing the
      primary airways and the lobes of each lung. Dichotomous branching leads to
      further extension of the airways. Grafting studies have demonstrated the
      importance of bronchial mesenchyme in inducing epithelial branching, but the
      significance of epithelial signaling has largely been unstudied. The morphogen
      Sonic hedgehog (Shh) is widely expressed in the foregut endoderm and is
      specifically upregulated in the distal epithelium of the lung where branching is
      occurring [2]. Ectopic expression of Shh disrupts branching and increases
      proliferation, suggesting that local Shh signaling regulates lung development
      [2]. We report here that Shh is essential for development of the respiratory
      system. In Shh null mutants, we found that the trachea and esophagus do not
      separate properly and the lungs form a rudimentary sac due to failure of
      branching and growth after formation of the primary lung buds. Interestingly,
      normal proximo-distal differentiation of the airway epithelium occurred,
      indicating that Shh is not needed for differentiation events. In addition, the
      transcription of several mesenchymally expressed downstream targets of Shh is
      abolished. These results highlight the importance of epithelially derived Shh in
      regulating branching morphogenesis of the lung.

PMID- 9768364
TI  - Dynamics and ultrastructure of developmental cell fusions in the Caenorhabditis
      elegans hypodermis.
AB  - Cell fusions produce multinucleate syncytia that are crucial to the structure of
      essential tissues in many organisms [1-5]. In humans the entire musculature, much
      of the placenta, and key cells in bones and blood are derived from cell fusion.
      Yet the developmental fusion of cell membranes has never been directly observed
      and is poorly understood. Similarity between viral fusion proteins and recently
      discovered cellular proteins implies that both cell-cell and virus-cell fusion
      may occur by a similar mechanism [6-8]. Paradoxically, however, fusion of
      enveloped viruses with cells involves an opening originating as a single pore [9
      11], whereas electron microscopy studies of cell-cell fusion describe
      simultaneous breakdown of large areas of membrane [12, 13]. Here, we have shown
      that developmental cell fusion is indeed consistent with initiation by a virus
      like, pore-forming mechanism. We examined live cell fusions in the epithelia of
      Caenorhabditis elegans embryos by a new method that integrates multiphoton,
      confocal, and electron microscopy. The fusion aperture always originated at a
      single point restricted to the apical adherens junction and widened slowly as a
      radial wavefront. The fusing membranes dispersed by vesiculation, rather than
      simple unfolding of the conjoined double bilayer. Thus, in these cells fusion
      appears to require two specialized sequential processes: formation of a unique
      primary pore and expansion of the opening by radial internalization of the
      interacting cell membranes.

PMID- 9768365
TI  - Life extension and stress resistance in Caenorhabditis elegans modulated by the
      tkr-1 gene.
AB  - The nematode Caenorhabditis elegans is widely used to study aging, development,
      behavior and other basic metazoan processes [1-3]. The only mutants directly
      identified on the basis of their extended longevity in any metazoan have been
      isolated in C. elegans [4,5]. All life-extension mutants (Age mutants) previously
      identified in C. elegans result from hypo-morphic or nullo-morphic mutations. We
      have identified a new class of gerontogene (a gene whose alteration causes life
      extension) that increases life span when overexpressed. The first gene in this
      class has been designated tyrosine kinase receptor-1 (tkr-1); it encodes a
      putative receptor tyrosine kinase. Overexpression of tkr-1 in transgenics
      increases longevity 40-100% (average 65%), confers increased resistance to heat
      and ultraviolet (UV) irradiation in transgenic nematodes, and does not alter
      development or fertility. Unlike previously identified gerontogenes, tkr-1
      positively modulates stress resistance and longevity. These results further
      support the positive relationship between increased stress resistance and
      increased longevity seen in all previously studied longevity mutants. This
      transgenic system is an effective means for identifying overexpression
      gerontogenes.

PMID- 9768366
TI  - A role of nicotinamide-induced increase in pancreatic beta-cell mass on blood
      glucose control after discontinuation of the treatment in partially
      pancreatectomized OLETF rats.
AB  - Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of NIDDM, is normoglycemic
      at a young age. However, they become hyperglycemic, even at a young age as a
      result of a 70% pancreatectomy, which is associated with insufficient
      proliferation of beta-cells. Administration of nicotinamide ameliorates the
      sustained hyperglycemia by increasing beta-cell proliferation. In order to
      further understand its mode of action, we studied how long nicotinamide is
      effective, in terms of ameliorating hyperglycemia, as evidenced by an increase in
      beta-cell mass, after its administration, in partially pancreatectomized OLETF
      rats. Male rats, 6 weeks of age, were allocated at random to two groups, 70%
      pancreatectomy (Px) and sham-pancreatectomy (sham). The Px group was divided into
      three subgroups, based on treatment with either nicotinamide (350 mg/kg),
      phlorizin (400 mg/kg) or saline, which continued until 4 weeks after surgery, and
      were sacrificed at 4, 6, or 8 weeks after surgery. A 70% Px resulted in sustained
      hyperglycemia in the saline-treated Px rats, which was ameliorated by
      administration of either phlorizin or nicotinamide, showing the non-fasting blood
      glucose levels reached to or near the levels found in the sham rats. After
      cessation of phlorizin injection, non-fasting blood glucose level increased
      rapidly, reaching the level of the saline-treated Px rats at the end of the
      experiment, whereas after cessation of nicotinamide injection, non-fasting blood
      glucose increased gradually to a level which was significantly lower than that
      observed in the saline-treated Px rats. An increased beta-cell mass, 62.7 +/-
      7.8% of total beta-cell mass induced by nicotinamide at 4 weeks, decreased
      gradually, reaching the level of pretreatment, 30.3 +/- 4.0% 4 weeks after
      cessation of the treatment. The findings in this study suggest that ameliorated
      hyperglycemia as a result of proliferated beta-cells during the administration of
      nicotinamide may results in showing beta-cell exhaustion (a majority of beta-cell
      degranulation) once stopping injection, as compared with phlorizin treated group
      in this model rat.

PMID- 9768367
TI  - Ultrastructural evaluation of B-cell recruitment in virgin and pregnant offspring
      of diabetic mothers.
AB  - Adult offspring of diabetic rat mothers display a disturbed glucose tolerance and
      gestational diabetes. The amount of endocrine pancreas and of B-cells is largely
      sufficient in these non-pregnant and pregnant youngsters. The present work aims a
      morphometric evaluation of B-cell activity in adult youngsters from control,
      mildly and severely diabetic mothers, in basal condition and in their adaptation
      to pregnancy. B-cells are divided, on basis of the ultrastructural morphology of
      their organelles, in dark non-activated B-cells and pale activated B-cells. These
      data are related to the concepts of functional B-cell heterogeneity and dose
      dependent recruitment of pancreatic B-cells on stimulation. The recruitment of B
      cells in each of the groups is evaluated from the proportion pale/dark B-cells.
      In control animals this is about 50/50, in both experimental groups there is a
      marked predominance of pale B-cells. During normal pregnancy, a shift occurs
      towards a majority of pale B-cells. In the offspring of diabetic mothers, the
      ratio does not further change during gestation. It can be concluded that the
      disturbance in B-cell stimulation and the development of gestational diabetes in
      offspring of diabetic mothers is associated with a maximal recruitment of the B
      cells already in basal non-pregnant condition.

PMID- 9768368
TI  - Comparison of NovoPen 3 and syringes/vials in the acceptance of insulin therapy
      in NIDDM patients with secondary failure to oral hypoglycaemic agents.
AB  - This open, randomised, cross-over study compared the acceptance and safety of
      NovoPen 3 with that of conventional syringes and vials when initiating insulin
      treatment in 96 NIDDM patients with secondary failure to oral hypoglycaemic
      agents. These patients had not previously been treated with insulin. All patients
      used each insulin administration system for 12 weeks. Group A started therapy
      using NovoPen 3 and crossed over to syringe/vial administration; Group B started
      with syringe/vial administration followed by NovoPen 3. In total, 78 patients
      completed the study. Most patients in Group A initially found the insulin
      injections very easy or easy and many of those who found injections easy at first
      found them very easy by the end of week 12. During the first period, patients in
      Group B found insulin administration more difficult than those in Group A.
      Injection pain was significantly lower with NovoPen 3 than with syringes and
      vials (P = 0.0018). Patients in Group B reported a significantly lower level of
      injection pain after the switch to using NovoPen 3 (P = 0.0003). Acceptance of
      insulin injections was significantly higher by patients using NovoPen 3 than by
      those using syringes and vials (P = 0.0059). Setting and drawing up the dose of
      insulin was also easier for patients using NovoPen 3 (P = 0.0490). At the end of
      the study, most patients (89.5% (68/76 replies)) said that they preferred NovoPen
      3 to syringes and vials. Glycaemic control improved compared with baseline after
      starting insulin therapy, with no differences between Groups A and B, or between
      the two injection systems. The number of reported hypoglycaemic episodes was very
      low and was not significantly different between Groups A and B, or between the
      two administration systems. No treatment-related adverse events were reported. We
      conclude that use of NovoPen 3 provides better acceptance of insulin injection
      than use of conventional syringes and vials during initiation of insulin therapy
      in NIDDM patients with secondary failure to treatment with oral hypoglycaemic
      agents.

PMID- 9768369
TI  - Antibodies to glutamic acid decarboxylase (GAD) in non-obese Japanese diabetics
      without insulin therapy: a comparison of two commercial RIA kits based on
      recombinant and pig brain GAD.
AB  - To compare the clinical usefulness of commercial radioimmunoassay (RIA) kits
      based on recombinant and pig brain GAD, we measured glutamic acid decarboxylase
      autoantibody (GADAb) titers in 125 non-obese (body mass index < 24) Japanese
      diabetics without insulin therapy using two commercial RIA kits based on
      recombinant human (rh) GAD65 (GADAb Cosmic) and purified pig brain native GAD
      (RIP Anti-GAD Hoechst). The frequencies of GADAb positivity using these two RIA
      kits (normal ranges; < 1.3 and < 4.0 U/ml, respectively) were about 4.8 (6/125)
      and 3.2% (4/125), respectively. The six patients found to be positive with RIA
      using GADAb Cosmic demonstrated significantly higher prevalence of NIDDM in their
      parents (P = 0.04), lower beta-cell function estimated by intravenous glucagon
      loading tests (P = 0.03) and higher prevalence of progression to insulin therapy
      (P = 0.0001). Five of these six patients slowly progressed to insulin-requiring
      status within 34 +/- 11 months of follow-up evaluation, and one of these five
      patients progressed to a completely insulin-dependent status within 30 months
      from the onset of diabetes. Of these six patients, two demonstrated chronic
      pancreatitis, three had chronic thyroiditis, and five showed HLA DR4.
      Interestingly, two of the six patients demonstrated very low GADAb titers (2.3
      and 2.9 U/ml), while RIP Anti-GAD Hoechst showed no positivity with the same
      sera. Based on the binding study after pre-incubation of unlabeled GADs, these
      low titrated GADAb were elucidated to be true specific reactions to rh GAD65
      alone. Moreover, one of the two patients with chronic thyroiditis and HLA DR4
      slowly progressed to insulin-requiring status over a period of 45 months. These
      findings suggest that the measurement of GADAb using a commercial assay kit with
      rh GAD65 may be more useful to detect non-insulin-dependent type I diabetics
      among non-obese patients than using a commercial kit with purified pig brain
      native GAD, especially among those with low GADAb titers.

PMID- 9768370
TI  - Pioglitazone enhances splanchnic glucose uptake as well as peripheral glucose
      uptake in non-insulin-dependent diabetes mellitus. AD-4833 Clamp-OGL Study Group.
AB  - To evaluate the effect of pioglitazone on insulin resistance in non-insulin
      dependent diabetes mellitus (NIDDM) patients, a double-blind placebo-controlled
      trial was carried out with 30 NIDDM patients. Twenty-one subjects, three on diet
      alone and 18 on sulfonylurea (SU), orally received 30 mg pioglitazone once daily
      for 12 weeks. Nine subjects, one on diet alone and eight on SU, received a
      matching placebo once daily for 12 weeks. Euglycemic (5.2 mmol/l)
      hyperinsulinemic (1200 pmol/l) clamp combined with an oral glucose load (OGL) was
      performed before and after 3-month treatment with pioglitazone or placebo to
      determine insulin-stimulated glucose disposal and splanchnic glucose uptake
      (SGU). No significant differences existed in the patients' characteristics,
      including age and body mass index, between the two study groups. The pioglitazone
      treatment increased the mean glucose infusion rate (GIR) prior to OGL from 8.2 +/
      2.2 to 9.2 +/- 2.0 mg/kg.min (mean +/- SD, P = 0.003) and increased the SGU rate
      from 28.5 +/- 19.4 to 59.4 +/- 27.1% (P = 0.010). The placebo treatment produced
      no significant changes in either GIR or SGU after treatment. A significant
      difference (P = 0.042) was observed in change of SGU between the pioglitazone and
      placebo treatment groups. In conclusion, the results indicate that pioglitazone
      is effective for ameliorating insulin resistance in NIDDM by enhancing SGU as
      well as peripheral glucose uptake.

PMID- 9768371
TI  - An atherogenic midband lipoprotein: a risk factor for coronary artery disease in
      diabetes mellitus with hyperlipidemia.
AB  - On polyacrylamide gel (PAG) disc electrophoresis of serum lipoproteins, the
      band(s) which migrates between pre beta- and beta-lipoproteins was more
      frequently observed in hyperlipidemics with diabetes mellitus (73%), than in
      those without diabetes mellitus (37%) (P < 0.01). Those bands were seen at three
      positions between pre beta- and beta-lipoproteins. A higher incidence of coronary
      artery disease (CAD) was observed in patients with midband as a shoulder of beta
      lipoproteins (44%), than in those without midband (11%) (P < 0.05) after the
      matching of other risk factors. These results suggest that midband as a shoulder
      of beta-lipoproteins may be a risk factor for CAD in diabetes mellitus with
      hyperlipidemia.

PMID- 9768372
TI  - Effect of acarbose on postprandial lipid metabolism in type 2 diabetes mellitus.
AB  - The effect of acarbose, an alpha-glucosidase inhibitor, on postprandial glucose
      and lipid metabolism was investigated in patients with type 2 diabetes mellitus.
      Twenty patients (10 men and 10 women) with type 2 diabetes mellitus were studied.
      A test meal was taken with or without 100 mg of acarbose. The levels of plasma
      glucose, and serum immunoreactive insulin, lipids, apolipoproteins, and remnant
      like particle cholesterol were investigated. Acarbose inhibited the postprandial
      increase of both plasma glucose and serum immunoreactive insulin. Acarbose also
      significantly suppressed the increase of serum triglycerides at 60, 90, and 120
      min (P < 0.05 to P < 0.01), and the increase of serum remnant-like particle
      cholesterol at 60 and 120 min (P < 0.05). Acarbose inhibited the postprandial
      decline of apolipoprotein C-II, and decreased the postprandial serum
      apolipoprotein C-III level. These results suggest that acarbose may improve
      postprandial hyperlipidemia as well as postprandial hyperglycemia in patients
      with type 2 diabetes mellitus.

PMID- 9768373
TI  - The effect of low intensity bicycle exercise on the insulin-induced glucose
      uptake in obese patients with type 2 diabetes.
AB  - OBJECTIVE: The present study was undertaken to reveal the effect of low intensity
      bicycle exercise on the insulin-induced glucose uptake in obese patients.
      SUBJECTS AND METHODS: Seven obese men with Type 2 diabetes (OBDM) and seven
      healthy young men (HY) participated in this study. The glucose infusion rate
      (GIR) was determined by glucose clamp procedure at an insulin infusion rate of 40
      mU m-2 min-1 (plasma insulin concentrations: 700-800 pmol l-1). Confirming
      stabilized GIR, a 30-min bicycle exercise was performed during the glucose clamp
      which was continued for 120 min after exercise. RESULTS: Average GIR in OBDM for
      last 30 min prior to exercise were significantly lower than HY (28.3 +/- 1.7,
      47.4 +/- 1.8 mumol kg-1 min-1 respectively, P < 0.05). GIR abruptly increased
      during exercise and gradually decreased after exercise to the nadir almost at the
      time from 30 to 60 min in recovery period in both groups. GIR in OBDM, however,
      gradually increased significantly over pre-exercise levels (P < 0.05), following
      exercise and reached the same levels compared to HY after 80 min of recovery
      period. CONCLUSION: These results indicated that in obese Type 2 diabetes, 30 min
      of low intensity bicycle exercise significantly enhances the lower level of
      insulin-induced glucose uptake shortly after exercise and might be useful for the
      treatment of post-prandial hyperglycemia.

PMID- 9768374
TI  - Peripheral neuropathy, hypertension, foot ulcers and amputations among Saudi
      Arabian patients with type 2 diabetes.
AB  - Three hundred and seventy-five Saudi Arabian patients with type 2 diabetes were
      consecutively examined for peripheral neuropathy, foot ulcers, amputations and
      hypertension. All the 46-69-year-old patients (n = 212) were compared to a
      corresponding Swedish group seen by the same physician using identical approach
      and definitions. Vibration sensitivity was examined using a tuning fork. Pin
      prick sensitivity using a needle on the plantar and dorsal aspects of the foot.
      Distal neuropathy was defined as complete absence of vibration and/or pin prick
      sensitivity in an extremity. With a diabetes duration of 10 or more years the
      prevalence of neuropathy among the 375 Saudi Arabians was 38% (95% confidence
      intervals 30-45); hypertension 19% (13-25) current and past ulcers 4.7% (1.3-8);
      amputations below ankle 3.4% (0.5-6). In the selected 46-69-year-old group
      prevalence of hypertension (17%), ulcers (2.3%) and amputation (1%) was
      significantly lower in the Saudi Arabian than in the Swedish patients. The
      frequencies reported here are the first from the Arab Peninsula. The Saudi
      Arabian patients with type 2 diabetes have the same prevalence of distal
      neuropathy as other ethnic groups. A low prevalence of hypertension is consistent
      with findings in expatriate and indigenous Arab groups with type 2 diabetes. The
      low occurrence of ulcers and amputations may be explained by different styles of
      footwear.

PMID- 9768375
TI  - Effects of genetic predisposition on proinsulin responses in Asian Indians.
AB  - This study was done in adult offspring of two diabetic (NIDDM) parents (ODP) to
      look for changes in specific insulin (insulin) and proinsulin responses due to
      strong familial background and also in different states of glucose intolerance.
      Equal numbers (20 in each group) of ODP with normal glucose tolerance (NGT),
      impaired glucose tolerance (IGT) and diabetes (DM) were chosen. Twenty, age and
      BMI matched healthy controls, without family history of diabetes, were also
      studied for comparison. Plasma specific insulin and proinsulin were measured by
      radioimmunoassays in fasting and 120' plasma samples collected during the GTT.
      Proinsulin to insulin ratio were calculated. Insulin resistance (IR-HOMA) was
      calculated. In NGT, fasting proinsulin-insulin ratio was significantly higher
      than the control value (P = 0.023). Insulin values at 120' was higher than
      control values, though it did not reach statistical significance. Proinsulin at
      120' was higher than controls (P = 0.016). In IGT, the fasting proinsulin to
      insulin ratio, the 120' proinsulin and insulin values were higher than controls
      (P = 0.048, 0.0013 and 0.0001, respectively). Fasting proinsulin-insulin ratio in
      IGT was similar to the value in NGT. In diabetic subjects proinsulin
      concentrations were significantly higher than controls at fasting (P = 0.0004),
      and 120' (P = 0.0007). The fasting values were higher compared to NGT also (P =
      0.037). Proinsulin-insulin ratios were higher than the values in controls (P =
      0.0008), IGT (P = 0.047) and NGT (P = 0.05). Diabetic subjects had higher fasting
      insulin values compared to the control values although between the groups no
      statistical significance was found (P = 0.22 by Kruscall Wallis test). At 120'
      both insulin and proinsulin values increased from NGT to IGT, but with
      development of diabetes a reduction was seen in the responses. Insulin resistance
      (IR-HOMA) increased steadily from NGT to diabetes. The difference between NGT and
      controls in IR was not statistically significant. This study of Asian Indian
      offspring of diabetic parents has shown that genetic predisposition to diabetes
      resulted in increased proinsulin to insulin ratio at the fasting state. Absolute
      hyperproinsulinaemia occurred only with development of diabetes.

PMID- 9768376
TI  - Intervention mapping: a process for developing theory- and evidence-based health
      education programs.
AB  - The practice of health education involves three major program-planning
      activities: needs assessment, program development, and evaluation. Over the past
      20 years, significant enhancements have been made to the conceptual base and
      practice of health education. Models that outline explicit procedures and
      detailed conceptualization of community assessment and evaluation have been
      developed. Other advancements include the application of theory to health
      education and promotion program development and implementation. However, there
      remains a need for more explicit specification of the processes by which one uses
      theory and empirical findings to develop interventions. This article presents the
      origins, purpose, and description of Intervention Mapping, a framework for health
      education intervention development. Intervention Mapping is composed of five
      steps: (1) creating a matrix of proximal program objectives, (2) selecting theory
      based intervention methods and practical strategies, (3) designing and organizing
      a program, (4) specifying adoption and implementation plans, and (5) generating
      program evaluation plans.

PMID- 9768377
TI  - Intervention mapping and the new health promotion.

PMID- 9768378
TI  - Preventing the spread of genital warts: using fear appeals to promote self
      protective behaviors.
AB  - A fear appeal campaign to decrease the spread of genital warts was conducted and
      evaluated. Theoretically guided by the Extended Parallel Process Model, this
      field study illustrated why fear appeal campaigns often appear to fail in public
      health arenas. Five hypotheses, which predicted when and under what conditions
      fear appeal campaigns would fail or succeed, were tested and supported. The
      results demonstrated that fear appeals can be powerful persuasive devices if they
      induce strong perceptions of threat and fear (which motivate action) and if they
      induce strong perceptions of efficacy with regard to a recommended response
      (which channels the action in a health protective direction). Recommendations to
      researchers and public health practitioners are offered.

PMID- 9768379
TI  - Social support and readiness to make dietary changes.
AB  - This article examines the relationship between reported social support and
      readiness to increase fruit and vegetable consumption, based on the
      Transtheoretical Stage of Change Model. Data were collected as part of the
      baseline assessments for a work site intervention study promoting increased
      consumption of fruits and vegetables. Among workers who did not live alone,
      household support was significantly higher for those of Hispanic and African
      American heritage than other groups, and was also higher among men, nonsmokers,
      and those living with adults compared to those living only with children. In
      multivariate analyses, coworker support was significantly associated with being
      in preparation compared to precontemplation/contemplation. Household support was
      not significantly related to readiness to change in multivariate analyses. The
      effectiveness of work site nutrition education interventions is likely to be
      enhanced by teaching participants to provide social support to coworkers and
      family members.

PMID- 9768380
TI  - Social support and coping behaviors of low-income families experiencing food
      insufficiency in North Carolina.
AB  - The Food Research and Action Center estimates that approximately 12% of all
      families with children younger than 12 years old experience food insufficiency in
      the United States. The authors conducted 16 focus groups with 141 participants,
      who were either at risk or experienced food insufficiency, to learn about coping
      strategies. Individual and network-level coping mechanisms were used to manage
      insufficient food supply. Social networks included family, friends, and
      neighbors. The assistance provided included food aid, information, and emotional
      support. Not all networks were relied on or accessed by everyone. Most
      participants reported that they relied on family members first, followed by
      friends, and then neighbors. Parents found reliance on anyone as stressful and
      often threatening. In conclusion, as the social welfare system becomes
      constrained, more and more households may experience food insufficiency.
      Responsive policies are therefore needed to assist low-income families.

PMID- 9768381
TI  - Practical assessment of adult literacy in health care.
AB  - Low literacy is a pervasive and underrecognized problem in health care
      Approximately 21% of American adults are functionally illiterate, and another 27%
      have marginal literacy skills. Such patients may have difficulty reading and
      understanding discharge instructions, medication labels, patient education
      materials, consent forms, or health surveys. Properly assessing the literacy
      level of individual patients or groups may avoid problems in clinical care and
      research. This article reviews the use of literacy assessments, discusses their
      application in a variety of health care settings, and cites issues providers need
      to consider before testing. The authors describe informal and formal methods of
      screening for reading and comprehension in English and Spanish including the
      Rapid Estimate of Adult Literacy in Medicine, the Wide Range Achievement Test-3,
      the Cloze procedure, the Test of Functional Health Literacy in Adults, and
      others. Practical implications and recommendations for specific use are made.

PMID- 9768382
TI  - Longitudinal study of relapse from AIDS-preventive behavior among homosexual men.
AB  - There is no viable alternative to the control of AIDS besides prevention; factors
      contributing to relapse from behaviors presumed to reduce risk of that disease
      were investigated. The authors studied 524 homosexual men who had refrained from
      or used condoms during receptive or insertive anal sex (RAS and IAS,
      respectively) for at least 12 months, contacting them at 6-month intervals
      thereafter to ascertain current practices. They determined, via interviews,
      personal traits, appraised stress of maintaining safer sex, mental health, life
      events, and efforts to cope with potential infection. Negative life events,
      personal control beliefs, problem-solving abilities, and coping via problem
      focused (e.g., seeking a monogamous union) rather than emotion-focused (e.g.,
      "when I need a cure, they will have one") behaviors were associated with RAS, but
      less so with IAS safer sex behaviors. These findings provide a basis for
      individual and community-level interventions to change behavior and reduce AIDS
      risk.

PMID- 9768383
TI  - Physical activity and minority women: a qualitative study.
AB  - Few physical activity research studies have been conducted with minority women.
      The purpose of this study was to explore patterns of physical activity among
      minority women. Focus groups were conducted with volunteers older than age 40.
      Each group was led by a trained moderator familiar with the ethnic community
      targeted. The sessions were audiotaped and professionally transcribed. Constructs
      were researched and codes were developed. Data were analyzed using NUD*IST
      qualitative analysis program. While participants did not identify themselves as
      "exercisers," they indicated they got enough physical activity from caregiving,
      housekeeping, and workday activities. The most common environmental barriers to
      becoming more physically active included safety, availability, and cost. Personal
      barriers included lack of time, health concerns, and lack of motivation. Results
      indicate the importance of terminology and assessment when conducting physical
      activity research in these populations. Also, results suggest many barriers are
      changeable with policies and interventions.

PMID- 9768384
TI  - Improving breast cancer control among Latinas: evaluation of a theory-based
      educational program.
AB  - The study evaluated a theory-based breast cancer control program specially
      developed for less acculturated Latinas. The authors used a quasi-experimental
      design with random assignment of Latinas into experimental (n = 51) or control (n
      = 37) groups that completed one pretest and two posttest surveys. The
      experimental group received the educational program, which was based on Bandura's
      self-efficacy theory and Freire's empowerment pedagogy. Outcome measures included
      knowledge, perceived self-efficacy, attitudes, breast self-examination (BSE)
      skills, and mammogram use. At posttest 1, controlling for pretest scores, the
      experimental group was significantly more likely than the control group to have
      more medically recognized knowledge (sum of square [SS] = 17.0, F = 6.58, p <
      .01), have less medically recognized knowledge (SS = 128.8, F = 39.24, p < .001),
      greater sense of perceived self-efficacy (SS = 316.5, F = 9.63, p < .01), and
      greater adeptness in the conduct of BSE (SS = 234.8, F = 153.33, p < .001).
      Cancer control programs designed for less acculturated women should use informal
      and interactive educational methods that incorporate skill-enhancing and
      empowering techniques.

PMID- 9768385
TI  - Fluorescein-stained capsulorhexis.

PMID- 9768386
TI  - About encircling haptics.

PMID- 9768387
TI  - Complications with the passport placement system.

PMID- 9768388
TI  - Consultation section. Refractive surgical problem.

PMID- 9768389
TI  - Blunt, bent needle for continuous curvilinear capsulorhexis.
AB  - We describe an anterior continuous curvilinear capsulorhexis (CCC) technique that
      uses a dull needle. The needle's blunt tip prevents inadvertent tearing of the
      anterior capsule, and its rough surface allows the surgeon to transmit a power
      vector of different amplitude and direction to the edge of the capsulorhexis to
      continue the tear as desired. For biomechanical reasons, we prefer an arcade
      shaped CCC because this configuration provides a greater circumference than a
      circular CCC. The blunt needle allows one to perform a single-step capsulorhexis
      in a safe and controlled manner and reduces surgical time. Even in cases of white
      and liquified cortex, the dull needle has proved a useful, safe tool.

PMID- 9768390
TI  - Axial, instantaneous, and refractive formulas in computerized videokeratography
      of normal corneas.
AB  - PURPOSE: To compare the values for corneal power determined by the axial,
      instantaneous and refractive formulas when imaging normal human corneas using
      computerized videokeratography. SETTING: Cullen Eye Institute, Baylor College of
      Medicine, Houston, Texas, USA. METHODS: This prospective clinical trial involved
      60 corneas of 30 normal volunteers. Computerized videokeratography was performed
      to determine corneal power at the center and the 1, 3, 5, and 7 mm zones using
      the 3 formulas. RESULTS: Mean central corneal power was 42.86 diopters (D) with
      each of the formulas. The mean corneal powers for the axial, instantaneous, and
      refractive formulas were 43.09, 43.21, and 42.98 D at the 1 mm zone; 43.10,
      42.92, and 43.46 D at the 3 mm zone; 42.75, 41.63, and 44.02 at the 5 mm zone;
      42.21, 40.30, and 44.79 D at the 7 mm zone, respectively. The differences among
      powers for the 3 formulas at the 3, 5, and 7 mm zones were statistically
      significant (P < .01). CONCLUSION: In normal corneas, clinically significant
      differences exist in the corneal power values calculated by the axial,
      instantaneous, and refractive formulas.

PMID- 9768391
TI  - Noncontact thermokeratoplasty to correct hyperopia induced by laser in situ
      keratomileusis.
AB  - PURPOSE: To evaluate the efficacy and safety of noncontact holmium:YAG (Ho:YAG)
      laser thermokeratoplasty (LTK) for treating hyperopia induced by laser in situ
      keratomileusis (LASIK). SETTING: Department of Ophthalmology, University of
      Alicante, Instituto Oftalmologico de Alicante, Alicante, Spain, and the
      University of Al-Azhar, Cairo, Egypt. METHODS: Noncontact LTK was applied to 13
      eyes (11 patients) with significant hyperopia after LASIK using a Ho:YAG laser
      (model gLase 210, Sunrise Technologies). Mean spherical equivalent before LTK was
      +4.60 diopters (D) +/- 1.40 (SD) (range +2.50 to +7.25 D). The results were
      evaluated 18 months after the LTK surgery. RESULTS: A significant myopic shift
      developed in all eyes that gradually receded to emmetropia 6 to 8 weeks after
      LTK. After 12 months, refraction was relatively stable. At 18 months, there was a
      statistically significant difference between the mean uncorrected visual acuity
      (UCVA) before LTK (0.19 +/- 0.09) and mean postoperative UCVA (0.61 +/- 0.22) (P
      < .005). At the end of the study, there was a mean increase of 4.10 +/- 1.12 D in
      central keratometric power. Total regression did not occur in any eye.
      CONCLUSION: Noncontact Ho:YAG LTK was safe and effective in correcting LASIK
      induced hyperopia. The cutting of Bowman's layer and a thinner corneal center may
      contribute to the stability of LTK in such cases.

PMID- 9768392
TI  - Diode laser thermokeratoplasty: application strategy and dosimetry.
AB  - PURPOSE: To investigate suitable application parameters for efficient hyperopic
      correction by laser thermokeratoplasty (LTK) using mid-infrared laser diodes.
      SETTING: Medical Laser Center Lubeck, Lubeck, Germany. METHOD: A tunable
      continuous-wave laser diode in the spectral range between 1.845 and 1.871 microns
      was used. Transmitted by waveguides, the laser energy was used to induce
      coagulations on freshly enucleated porcine eyes to increase corneal curvature.
      The coagulations were equidistantly applied by a fiber-cornea contact and a
      noncontact focusing device that were adjusted on a ring concentric to the corneal
      apex. Different laser parameters and application geometries were evaluated.
      Refractive changes were measured by computer-assisted corneal topography before
      and after treatment. Polarization light microscopy and temperature calculations
      were used to analyze the coagulations. RESULTS: Because of the tunability of the
      laser diode, the influence of the corneal absorption coefficient (between 0.9 and
      1.6 mm-1) on the refractive change could be measured. A laser power between 125
      and 200 mW was adequate to achieve refractive changes up to 10.0 diopters. In the
      preferable focusing device, the refractive change increased almost
      logarithmically with the irradiation time up to 15 seconds. The number of
      coagulations on a fixed application ring showed no significant influence on
      refractive change; however, it showed an almost linear decrease with increasing
      ring diameter from 5.0 to 10.0 mm. Histological analysis revealed 3 stages of
      thermal damage. CONCLUSION: Diode LTK provided defined and uniform coagulations
      when using a well-adapted focusing device, resulting in sufficient refractive
      change. The results indicate that diode LTK is superior to pulsed holmium LTK.

PMID- 9768393
TI  - Laser in situ keratomileusis after photorefractive keratectomy for myopic
      regression.
AB  - PURPOSE: To assess the efficacy and safety of laser in situ keratomileusis
      (LASIK) for regression after excimer laser photorefractive keratectomy (PRK).
      SETTING: Eye Research Center, Istanbul University, Istanbul, Turkey. METHODS:
      Laser in situ keratomileusis to treat residual myopia ranging from 1.50 to 12.50
      diopters (D) (mean 5.96 D +/- 3.06 [SD]) was performed in 45 eyes of 25 patients.
      Cylindrical corrections were done in 7 eyes (15.6%) and spherical ablations, in
      38 (84.4%). The mean interval between primary PRK and LASIK retreatment was 18.50
      +/- 8.12 months. The procedure was performed under a hinged corneal flap using
      the Chiron Automated Corneal Shaper and Chiron Keracor 116 excimer laser.
      RESULTS: Six months after LASIK retreatment, mean spherical equivalent refraction
      was -0.67 +/- 0.77 D. Thirty-six eyes (80%) were within +/- 1.00 D of emmetropia.
      Uncorrected visual acuity was 20/40 or more in 31 eyes (68.9%); 2 eyes (4%) lost
      2 lines of best spectacle-corrected visual acuity. There was no statistically
      significant difference in corneal haze before and after LASIK. CONCLUSION: Laser
      in situ keratomileusis was safe and effective for treating residual myopia after
      excimer laser PRK.

PMID- 9768394
TI  - Corneal topography in Ehlers-Danlos syndrome.
AB  - PURPOSE: To assess the use of corneal topography in conjunction with slitlamp
      biomicroscopy and retinoscopy to diagnose keratoconus in a large group of
      patients with Ehlers-Danlos syndrome (EDS). SETTING: Kresge Eye Institute, Wayne
      State University, Detroit, Michigan, USA. METHODS: Thirty-six patients (72 eyes)
      with genetically typed EDS had slitlamp biomicroscopy, retinoscopy, and
      videokeratography with the EyeSys instrument. The presence or absence of slitlamp
      keratoconus findings was correlated to a presumptive diagnosis based on corneal
      topography using derived topographic indexes associated with keratoconus. These
      topographic indexes included central corneal power, (CCP), difference in CCP,
      inferosuperior asymmetry (I-S) value, and asphericity (Q). Axial and profile
      difference maps were generated and analyzed for findings suggestive of
      keratoconus. RESULTS: In 72 eyes, no keratoconus was found using slitlamp
      biomicroscopy. No eye had an I-S value greater than 1.60 diopters (D), 2 eyes had
      a CCP greater than 46.50 D, and 2 eyes had a Q value less than -1.00. Eight of 36
      pairs of eyes had an intereye CCP greater than 0.92 D. In both eyes of the
      patient with Q values less than -1.00 the profile difference maps were mildly
      abnormal. CONCLUSIONS: Slitlamp biomicroscopy of the cornea was unremarkable in
      all patients. Only 1 patient had Q values and profile difference maps that were
      mildly suggestive of keratoconus. Even after adding topography to the
      examination, it appears that keratoconus in a known population of patients with
      EDS remains rare.

PMID- 9768395
TI  - Anterior capsule contraction with foldable silicone intraocular lenses.
AB  - PURPOSE: To examine the causes signs, and symptoms of anterior capsule
      contraction syndrome and the response to neodymium YAG (Nd:YAG) anterior
      capsulotomy. SETTING: Madigan Army Medical Center, Tacoma, Washington, USA.
      METHODS: This retrospective review comprised 70 cases of phacoemulsification with
      foldable plate-haptic silicone intraocular lens (IOL) implantation. Patients who
      developed anterior capsule contraction postoperatively, defined as the anterior
      capsule being visible through an undilated pupil, had a radial anterior
      capsulotomy with an Nd:YAG laser. Variables analyzed were visual acuity,
      subjective complaints, associated inflammation, and IOL decentration. RESULTS:
      Ten eyes of 9 patients (14%) developed anterior capsule contraction and had
      Nd:YAG laser radial anterior capsulotomy. Three of 9 patients reported decreased
      visual acuity and glare. Two other patients had chronic anterior chamber
      inflammation unresponsive to steroids after surgery that resolved after Nd:YAG
      anterior capsulotomy. Intraocular lens decentration was observed in 3 patients
      before the Nd:YAG capsulotomy. Posterior lens dislocation occurred in 1 patient
      after capsulotomy and required surgical lens exchange. CONCLUSION: One-piece
      foldable silicone IOLs may not provide enough peripheral capsule expansion.

PMID- 9768396
TI  - Cartridge cracks during foldable intraocular lens insertion.
AB  - PURPOSE: To assess the incidence of cartridge cracks during foldable intraocular
      lens (IOL) insertion and to determine factors that play a role in the development
      of these cracks. SETTING: Leesburg Regional Ambulatory Surgical Care Center,
      Leesburg, Florida, USA. METHODS: Small incision cataract surgery was performed in
      350 consecutive cases. A foldable silicone IOL (Allergan Medical Optics SI-40)
      was inserted in all cases using the Unfolder cartridge and 3 viscoelastic agents:
      sodium hyaluronate (Healon, Vitrax) and sodium chondroitin sulfate-sodium
      hyaluronate (Viscoat). RESULTS: Cartridge cracks occurred in 52 eyes (14.86%).
      Almost all cracks (98.1%) occurred in cases in which Healon was used to load the
      IOL. In each case of a cracked cartridge, there was evidence of the plunger
      overriding the optic edge. CONCLUSIONS: We recommend the use of chondroitin-based
      viscoelastic agents to load the SI-40 foldable IOL to minimize the risk of
      cartridge cracks. Modifications in the design of the IOL inserter may eliminate
      the problem of cartridge cracks.

PMID- 9768397
TI  - Transscleral fixation of acrylic intraocular lenses in the absence of capsular
      support through 3.5 mm self-sealing incisions.
AB  - PURPOSE: To evaluate the safety and efficacy of transscleral ciliary sulcus
      fixation of acrylic intraocular lenses (IOLs) through small incisions in the
      management of secondary IOL implantation. SETTING: Department of Ophthalmology,
      Osaka Rosai Hospital, Osaka, Japan. METHODS: This retrospective study consisted
      of 28 patients (30 eyes) who had transscleral fixation of acrylic IOLs through
      3.5 mm incisions. All patients were followed for a minimum of 6 months in several
      different clinical settings. Data on visual acuity, keratometry, and central
      corneal endothelial cell count were evaluated preoperatively and postoperatively.
      The refractive error achieved and incidence of postoperative complications were
      determined. RESULTS: Uncorrected visual acuity (UCVA) improved in all eyes. Of
      the 18 eyes without pre-existing pathology, 11 (61.1%) had a UCVA of 20/40 or
      better from 1 week postoperatively. Best corrected visual acuity was unchanged in
      24 eyes (80.0%) and improved by 2 Snellen lines or more in 5 eyes (16.7%) at the
      final examination. Self-sealing wound adaptation was achieved in 25 eyes (83.3%).
      The mean scalar shift in keratometric cylinder was 1.25 diopters (D) at 1 day
      postoperatively, 1.17 D at 1 week, and 1.06 D at 3 months. The rate of central
      corneal endothelial loss 6 months postoperatively averaged 7.84%. No
      intraoperative complications that were directly associated with acrylic IOL
      implantation occurred. Postoperative complications that included transient ocular
      hypertension, slight vitreous hemorrhage, and IOL malposition were found in a
      small population but resolved spontaneously without further surgical
      intervention. CONCLUSIONS: The good visual outcomes and low incidence of
      complications achieved in the present study indicate that acrylic IOLs positioned
      through small incisions might be considered for ciliary sulcus fixation. However,
      evaluation of this technique in a large population over the long term is
      required.

PMID- 9768398
TI  - New classification of capsular block syndrome.
AB  - PURPOSE: To propose a new classification of capsular block syndrome (CBS) to
      improve understanding of the etiology and provide effective treatment. SETTING:
      Shohzankai Medical Foundation, Miyake Eye Hospital, Nagoya, and Japanese Red
      Cross Society, Wakayama Medical Center, Wakayama, Japan. METHODS: Three groups of
      eyes with CBS were reviewed: eyes originally reported and diagnosed as having
      CBS; eyes experiencing CBS after hydrodissection and luxation of the lens
      nucleus; and eyes with CBS accompanying liquefied aftercataract or capsulorhexis
      related lacteocrumenasia. RESULTS: In all 3 groups, the CBS occurred in eyes with
      a continuous curvilinear capsulorhexis (CCC). It was characterized by
      accumulation of a liquefied substance within a closed chamber inside the capsular
      bag, formed because the lens nucleus or the posterior chamber intraocular lens
      (IOL) optic occluded the anterior capsular opening created by the CCC. Depending
      on the time of onset, CBS can be classified as intraoperative (CBS seen at the
      time of lens luxation following hydrodissection), early postoperative (original
      CBS), and late postoperative (CBS with liquefied aftercataract or
      lacteocrumenasia). The etiology of the accumulated substance and the method of
      treatment are different in each type. CONCLUSION: Capsular block syndrome is a
      complication of cataract/IOL surgery that can occur during and after surgery.
      Correctly identifying the type of CBS is crucial to understanding the nature and
      effective treatment of this disorder.

PMID- 9768399
TI  - Measuring the anterior capsule opening after cataract surgery to assess capsule
      shrinkage.
AB  - PURPOSE: To measure anterior capsule opening (ACO) size after acrylic intraocular
      lens (IOL) implantation and study the natural course of ACO reduction. SETTING:
      Kimura Eye and Internal Medicine Hospital, Hiroshima, Japan. METHODS: This study
      comprised 32 patients (38 eyes) having continuous curvilinear capsulorhexis,
      phacoemulsification, acrylic IOL implantation, and a self-sealing incision
      performed by 1 surgeon. A retroillumination photograph of the ACO was obtained
      with the Anterior Eye Segment Analysis System and converted to a computer image.
      The images were used to measure ACO size postoperatively and calculate the
      reduction ratio. Follow-up was 6 months. RESULTS: The postoperative reduction
      ratio in ACO size was 2.14% at 1 week, 3.83% at 1 month, 4.29% at 3 months, and
      5.03% at 6 months. In a few cases, the reduction was progressively severe
      throughout the follow-up. CONCLUSIONS: The anterior capsule opening shrank
      rapidly during the first month after acrylic IOL implantation, followed by a
      slower progressive reduction in the subsequent 6 months. When severe, progressive
      shrinkage occurs, an anterior neodymium:YAG laser capsulotomy should be performed
      within 2 months postoperatively.

PMID- 9768400
TI  - Effect of intraocular lens design on neodymium:YAG laser capsulotomy rates.
AB  - PURPOSE: To compare the effect of 2 poly(methyl methacrylate) (PMMA), 1-piece
      biconvex intraocular lens (IOL) designs on the cumulative frequency of
      neodymium:YAG (Nd:YAG) laser posterior capsulotomy. SETTING: Department of
      Ophthamology, Mayo Clinic, Rochester, Minnesota, USA. METHODS: This retrospective
      study evaluated 369 eyes that had phacoemulsification with continuous curvilinear
      capsulorhexis (CCC) and IOL implantation in the capsular bag. Patients were
      placed in 1 of 2 groups based on the 1-piece, biconvex PMMA IOL design: large
      IOL, with a lens diameter of 13.50 to 13.75 mm, optic size of 6.5 mm, and 10
      degree haptic angulation; small capsular IOL, with a lens diameter of 12.0 to
      12.5 mm, optic size of 5.5 mm, and 2 degree haptic angulation. RESULTS: Using
      Kaplan-Meier analysis, the frequency of Nd:YAG laser posterior capsulotomy 1, 2,
      and 3 years after cataract surgery was 1.6, 12.3, and 26.5%, respectively, in the
      large IOL group and 3.4, 9.5, and 23.5%, respectively, in the small capsular IOL
      group. The cumulative frequency of Nd:YAG laser capsulotomy was not statistically
      different between the 2 groups. CONCLUSION: After phacoemulsification and CCC,
      there was no significant difference in the Nd:YAG laser capsulotomy rate in eyes
      with a small, capsular design, 1-piece, biconvex PMMA IOL and those with a
      larger, angulated, 1-piece, biconvex PMMA IOL.

PMID- 9768401
TI  - Effect of aspirin intake on bleeding during cataract surgery.
AB  - PURPOSE: To study the association between chronic intake of aspirin and
      intraoperative bleeding during cataract surgery and the effect of discontinuing
      the medication before surgery. SETTING: Department of Ophthalmology, Meir
      Hospital, Sapir Medical Center, Kfar-Saba, Israel. METHODS: Sixty-one patients
      having cataract surgery and receiving aspirin to prevent thromboembolic events
      were divided into 3 groups: Group A, continuation of the medication; Group B,
      cessation of aspirin intake for 2 to 5 days before surgery; Group C, cessation of
      medication for 7 to 10 days before surgery. Blood tests of coagulation
      parameters, a detailed questionnaire, and 1 day and 1 week follow-up were
      evaluated. RESULTS: There were no significant differences in blood tests and the
      amount and incidence of intraoperative bleeding among the 3 groups. Diathermy was
      used somewhat more in Group A; however, there was no difficulty stopping the
      bleeding in any case and discontinuation of the medication had no effect on the
      intraoperative course or postoperative outcome. CONCLUSIONS: Aspirin intake was
      not associated with significant intraoperative bleeding; thus, discontinuation of
      aspirin is usually not indicated. Clear corneal phacoemulsification is
      advantageous in patients receiving antiplatelet therapy.

PMID- 9768402
TI  - Topical plus subconjunctival anesthesia for phacotrabeculectomy: one year follow
      up.
AB  - PURPOSE: To evaluate the results of topical plus subconjunctival anesthesia for
      phacotrabeculectomy surgery and postoperative glaucoma control over 1 year.
      SETTING: Pacific Eye Center, Brisbane, Australia. METHODS: In this retrospective
      study of consecutive patients with glaucoma and cataract, topical plus
      subconjunctival anesthesia was used for combined phacoemulsification, posterior
      chamber intraocular lens implantation, and trabeculectomy (phacotrabeculectomy).
      Patients with proliferative diabetic retinopathy or neovascular glaucoma were
      excluded. RESULTS: Thirty-eight eyes had phacotrabeculectomy using topical plus
      subconjunctival anesthesia over 2 years. Patients reported no discomfort
      intraoperatively or postoperatively, and none required intravenous sedation.
      Eighty-one percent of patients achieved a best corrected visual acuity of 20/40
      or better 6 months after surgery. Mean drop in intraocular pressure (IOP) was
      5.91 mm Hg at 3 months and 5.86 mm Hg at 12 months, at which time IOP was
      controlled without additional medication in 72% of patients. There were no
      serious complications postoperatively. CONCLUSION: In this series, no patient
      reported intraoperative or postoperative discomfort and surgical results were
      excellent in terms of visual outcome and IOP control.

PMID- 9768403
TI  - Phacofracture versus phacoemulsification in eyes with age-related cataract.
AB  - PURPOSE: To compare manual phacofracture and phacoemulsification techniques.
      SETTING: Dr. Rajendra Prasad Centre for Ophthalmic Sciences, New Delhi, India.
      METHODS: This prospective, randomized study comprised 60 cases of age-related
      cataract randomly divided into 2 groups: 30 eyes had phacoemulsification and 30,
      manual phacofracture using a trisection technique. Postoperative evaluation was
      at 1 day, 1 and 6 weeks, and 3 months. The parameters evaluated were amounts of
      viscoelastic material and irrigating fluid used, the time required to manage the
      nucleus, postoperative best corrected visual acuity, endothelial cell loss, and
      complications. RESULTS: Mean viscoelastic material used intraoperatively (3.69 mL
      +/- 0.81 [SD] versus 1.76 +/- 0.54 mL) and the time required to manage the
      nucleus (7.78 +/- 2.07 minutes versus 2.53 +/- 1.18 minutes) were significantly
      greater in the phacofracture than in the phacoemulsification group, respectively.
      Best corrected visual acuity was significantly better in the phacoemulsification
      group on the first postoperative day; 64% had a visual acuity of 6/9 or better
      versus 37% in the phacofracture group. Endothelial cell loss at 3 months was
      17.66 +/- 3.65% in the phacofracture group and 12.03 +/- 3.06% in the
      phacoemulsification group and central corneal edema persisting for more than 1
      week, 7 and 0 cases, respectively. The differences between groups were
      statistically significant. CONCLUSION: More experience in and further
      modification of the manual phacofracture technique are required before it can be
      recommended as a safe alternative to phacoemulsification.

PMID- 9768404
TI  - Metallic fragment deposits during phacoemulsification.
AB  - PURPOSE: To describe the nature and origin of foreign metallic intraocular bodies
      appearing after phacoemulsification. SETTING: Department of Ophthalmology,
      University Hospital of San Juan, Alicante, Spain. METHODS: Two metallic
      particles, 1 extracted during surgery and the other from a patient in whom
      surgery had been performed, were studied by scanning electronic microscopy and X
      ray dispersive energy spectroscopy. Also evaluated were all metallic elements
      used in phacoemulsification including phaco tips, Sinskey hooks, and handpieces.
      A morphologic analysis at various magnifications was performed and the
      composition of the elements studied. RESULTS: Scanning electronic microscopy
      showed irregularities of the phaco tip and Sinskey hook after their use.
      Spectrographic analysis found that the phaco tip was mainly aluminum and
      titanium; the Sinskey hook, iron, chromium, cobalt, and nickel; the handpiece,
      iron, chromium, and nickel; and the 2 metallic particles, iron, chromium, and
      nickel, the same as the handpiece. CONCLUSION: The metallic particles extracted
      corresponded to those of the phaco handpiece. Vibration during prolonged use of
      the phacoemulsifier probably caused these particles to chip off the handpiece.

PMID- 9768405
TI  - Immunolocalization of prolyl 4-hydroxylase in rabbit lens epithelial cells.
AB  - PURPOSE: To localize the enzyme prolyl 4-hydroxylase in the crystalline lens and
      determine the ability of lens epithelial cells (LECs) to synthesize procollagen.
      SETTING: Research laboratory, Department of Ophthalmology, Wakayama Medical
      College, Wakayama, Japan. METHODS: Phacoemulsification and aspiration of the
      crystalline lens followed by implantation of a poly(methyl methacrylate)
      intraocular lens (IOL) were performed in 1 eye each of 6 albino rabbits; the eye
      was enucleated 1 or 2 months later. Crystalline lenses were also extracted from
      the eyes of 2 rabbits. These samples were processed for immunohistochemical
      detection of the alpha- and beta-subunits of prolyl 4-hydroxylase. RESULTS: A
      monolayer of LECs was detected on the inner surface of the intact anterior
      capsule. Antibodies directed against both subunits of prolyl 4-hydroxylase
      reacted strongly to LECs proliferating on capsules with IOLs, whereas little or
      no reaction was observed in quiescent LECs or in the regenerated lenticular
      structure. CONCLUSION: The presence of prolyl 4-hydroxylase in LECs proliferating
      on the inner surface of the lens capsule suggests that these cells are involved
      in the production of procollagen and fibrosis during capsular injury and repair.
      Suppression of prolyl 4-hydroxylase activity may prevent the capsule
      opacification that results from cataract removal and IOL implantation.

PMID- 9768406
TI  - Immunolocalization of hyaluronan and CD44 in quiescent and proliferating human
      lens epithelial cells.
AB  - PURPOSE: To investigate the role of hyaluronan and its receptor CD44 in capsular
      repair, their localization in opacified human posterior capsules and in lens
      epithelial cells (LECs) was assayed. SETTING: Research laboratory, Department of
      Ophthalmology, Wakayama Medical College, Japan. METHODS: In 8 patients, circular
      sections of the anterior capsules obtained during cataract surgery, the extracted
      crystalline lens, and the opacified lens capsules resulting from intraocular lens
      implantation were examined immunohistochemically to detect hyaluronan or CD44.
      RESULTS: Both hyaluronan and CD44 were found in the extracellular matrix that
      accumulated on the inner surface of the capsular bags. In contrast, LECs
      exhibited immunoreactivity to CD44 but not to hyaluronan. CONCLUSIONS: The cell
      surface antigen CD44 was expressed ubiquitously by LECs. Expression of its ligand
      hyaluronan by proliferating LECs suggests that this glycosaminoglycan may be
      important in the development of posterior capsule opacification.

PMID- 9768407
TI  - Pupillary block after pupillary capture of an AcrySof intraocular lens.
AB  - A 54-year-old man developed pupillary block resulting from pupillary capture 2
      months after uneventful phacomulsification and AcrySof intraocular lens (IOL)
      implantation. The IOL was placed in the bag through a 6.0 mm continuous
      curvilinear capsulorhexis. The glaucoma was treated with intravenous drip
      infusion of a hyperosmotic diuretic, followed by peripheral iridectomy,
      iridocapsular synechiolysis, and IOL repositioning. The IOL loops were located
      completely in the bag. However, pupillary capture recurred 3 weeks after the
      surgery, at which time intraocular pressure was normal. The flexibility of the
      IOL optic and its large overall length and rigid, low-angulated loops were the
      probable causes for the recurrence of the pupillary capture. The IOL was
      exchanged for a sulcus-fixated, single-piece poly(methylmethacrylate) lens with
      10 degree angulated loops. Pupillary capture did not recur during the follow-up.

PMID- 9768408
TI  - Silicone intraocular lens encapsulation by shrinkage of the capsulorhexis
      opening.
AB  - We report a case of an 80-year-old woman who developed complete opacification and
      contraction of the continuous curvilinear capsulorhexis opening 4 months after
      having phacoemulsification and implantation of a silicone plate-haptic
      intraocular lens. We performed a neodymium:YAG laser capsulotomy without
      complication.

PMID- 9768409
TI  - Interface keratitis-induced stromal thinning: an early postoperative complication
      of laser in situ keratomileusis.
AB  - Two patients had bilateral laser in situ keratomileusis on the same day at the
      same center. Both developed severe interface inflammation in the second of the 2
      eyes treated, which led to stromal thinning corneal haze, and resultant
      hyperopia. These symptoms partially resolved over 7 weeks of follow-up.

PMID- 9768410
TI  - Keratitis complicated by endophthalmitis 3 years after astigmatic keratotomy.
AB  - Endophthalmitis after keratotomy is rare and usually occurs soon after surgery. A
      56-year-old woman with mild dry-eye symptoms developed keratitis complicated by
      endophthalmitis 3 years after astigmatic keratotomy (AK). The keratitis lasted
      for less than 1 day in the upper keratotomy incision. Corneal cultures yielded.
      Pseudomonas aeruginosa. Keratitis progressed to endophthalmitis 1 day after the
      detection of keratitis. The inflammation was controlled with intravitreal,
      subconjunctival, topical, and systemic antibiotics. This case demonstrates the
      potential risk of endophthalmitis developing very shortly after late keratitis of
      AK incisions. Vigorous early treatment and close follow-up seem justifiable in
      any keratitis associated with a keratotomy incision.

PMID- 9768411
TI  - Toluidine blue: proceed with caution?

PMID- 9768412
TI  - Pretherapy dental decisions in patients with head and neck cancer. A proposed
      model for dental decision support.
AB  - OBJECTIVE: The proposed model was designed to function as a tool for the
      development and testing of evidence-based clinical guidelines for the pretherapy
      oral screening and dental management of patients with head and neck cancer. STUDY
      DESIGN: Methods of clinical decision analysis were used to analyze the decision
      dilemma and construct a decision algorithm and decision tree. The robustness of
      the model was tested by means of a probabilistic sensitivity analysis with second
      order Monte Carlo simulations (n = 10.000). RESULTS: Clinical criteria for
      evaluating dental pathologic conditions and malignancy- and patient-related
      conditions were transformed in probability estimates. The tradeoffs between the
      benefits and drawbacks of the dental intervention were integrated into the model
      to identify the optimal option for dental intervention. The calculation process
      of "folding back and averaging out" the decision tree enabled the identification
      of the optimal options for dental intervention in four different pretherapy risk
      conditions. CONCLUSIONS: A priori testing of the proposed model with 95%
      confidence intervals suggests that it has a great potential for solving clinical
      dilemmas associated with pretherapy dental decision-making. In addition, it seems
      a useful tool for the development of evidence-based clinical guidelines. A
      posteriori clinical testing should further validate the model before its
      assimilation into clinical practice takes place.

PMID- 9768413
TI  - Importance of bone graft quality for implant integration after maxillary sinus
      reconstruction.
AB  - OBJECTIVE: The aim of this study was to determine whether bone quality, as
      assessed by osteometry and histologic parameters, can be used to predict implant
      integration in conjunction with maxillary sinus reconstruction. STUDY DESIGN:
      Twelve patients with severely atrophied maxillary alveolar processes were treated
      through use of a two-stage surgical reconstructive strategy with implant
      placement 4 months after bone grafting. Bone biopsy specimens taken from the
      iliac crest peroperatively and from the sinus inlay sites 1, 2, 4, 6, or 12
      months postoperatively were analyzed by light microscopy and osteomorphometry.
      Bone mineral content was measured by osteometry. RESULTS: Osteometric and
      osteomorphometric data (trabecular bone volume [%], assessment of chromatin
      staining, and an osteocyte index) registered for the biopsy specimens were not
      statistically correlated with implant failure. CONCLUSIONS: Prognostic evaluation
      of implant survival is difficult. The tested methods did not contribute to the
      improvement of guidelines for the clinical handling of these patients.

PMID- 9768414
TI  - Comparison of magnetic resonance imaging and gross findings regarding masseter
      muscle aponeuroses in cadavers.
AB  - OBJECTIVES: The main objective of this study was to compare the actual
      distribution and thickness of aponeuroses in cadavers with the distribution and
      thickness as determined by means of magnetic resonance imaging for the sake of
      evaluating magnetic resonance imaging as a diagnostic modality for assessing
      masseter muscle aponeuroses. STUDY DESIGN: The aponeuroses of 26 masseter muscles
      from 13 intact cadavers were examined by magnetic resonance imaging. RESULTS: The
      ratio of concordance between gross findings and magnetic resonance imaging
      findings was 99.0%, although depiction of thin parts of the aponeuroses on
      magnetic resonance imaging was poor. CONCLUSIONS: Magnetic resonance imaging was
      useful as a diagnostic modality in the assessment of masseter muscle aponeuroses.
      Aponeuroses were distributed throughout almost the entire masseter muscle,
      although almost no aponeuroses were seen below the lower half of the anterior
      margin. This was thought to be a characteristic finding of masseter aponeuroses.

PMID- 9768415
TI  - Mandibular height asymmetry following experimentally induced temporomandibular
      joint disk displacement in rabbits.
AB  - OBJECTIVE: The purpose of this study was to test the hypothesis that nonreducing
      disk displacement of the temporomandibular joint causes mandibular asymmetry.
      STUDY DESIGN: Unilateral anterior temporomandibular joint disk displacement with
      intact posterior disk attachment was surgically created in the right joints of
      seven growing rabbits. In each of seven sham animals, the right temporomandibular
      joint was surgically opened without any disk manipulation. Seven animals served
      as references. For identification of ramal growth and inferior growth at the
      mandibular base, tantalum implants were inserted into the mandibular body.
      Lateral cephalograms were exposed repeatedly throughout the 3-month investigation
      period. Kruskal-Wallis one-way analysis of variance was used to compare the
      groups. RESULTS: Compared with the sham and reference groups, the experimental
      group exhibited a deviant growth pattern, with inferiorly directed growth along
      the mandibular base and in the gonial area. The ramal height was significantly
      shorter on the side with disk displacement. No significant side difference was
      present in the sham and reference groups. CONCLUSIONS: Disk displacement can
      cause mandibular asymmetry in growing rabbits, including shortening of the
      mandibular ramus and excessive inferiorly directed bone growth along the lower
      border of the mandible.

PMID- 9768416
TI  - The relationships among fluoride, cariogenic oral flora, and salivary flow rate
      during radiation therapy.
AB  - Changes in the quantity of Streptococcus mutans, Lactobacillus species, and yeast
      Candida species were assessed in a cancer population undergoing head and neck
      radiation. The purpose of this study was to evaluate the effectiveness of a
      custom vinyl tray-applied fluoride gel to control cariogenic bacteria in a group
      experiencing hyposalivation because of radiation treatment. Twenty-two subjects
      participated in the study and served as their own controls. Whole resting and
      whole stimulated saliva were collected at weekly appointments beginning 1 week
      before and concluding 4 weeks after radiation therapy. Colony-forming units per
      mL of Streptococcus mutans and Lactobacillus species and semiquantitative counts
      of Candida species (0 = none; 1 = light; 2 = moderate; 3 = heavy) were determined
      from collected saliva. All patients were provided with custom vinyl vacuform
      mouthguards to be used daily with neutral fluoride gel (1.1% sodium fluoride).
      Whole stimulated and resting saliva productions decreased by 36.67% and 47.9%,
      respectively, by the end of 1 week of radiation therapy, and they remained low.
      No significant changes in cariogenic oral flora were seen during and early after
      radiation therapy, despite xerostomia. However, colonization by Candida albicans
      increased during radiation therapy for oropharyngeal cancers. Findings from this
      study suggest that changes in cariogenic flora may be suppressed through the use
      of daily topical neutral sodium fluoride gels and that colonization by Candida
      albicans increase during radiation therapy.

PMID- 9768417
TI  - Bell's palsy associated with herpes simplex gingivostomatitis. A case report.
AB  - Bell's palsy is a sudden, isolated, peripheral facial paralysis caused by various
      known and sometimes unknown factors. The case of an 18-year-old man who developed
      Bell's palsy after onset of primary herpetic gingivostomatitis is presented.
      Although Bell's palsy has already been associated with herpes simplex virus type
      1, the described case is the first in the literature in which enzyme-linked
      immunosorbent assays for immunoglobulin G to herpes simplex virus type 1 and
      herpes simplex virus type 1 culture were both positive. The recent literature
      regarding the possible relationship between herpes simplex virus type 1 and
      Bell's palsy is reviewed and discussed.

PMID- 9768418
TI  - Dento-maxillofacial sequelae in a child treated for a rhabdomyosarcoma in the
      head and neck. A case report.
AB  - This case report describes severe dento-maxillofacial defects after
      chemoradiation therapy in a child aged 9 years 6 months with a parameningeal
      rhabdomyosarcoma. A clinical and radiologic (apical dental radiographs,
      orthopantograph, lateral skull roentgenogram) dental follow-up over 4 years
      showed such dental abnormalities as root blunting, mild to severe root
      shortening, premature closure of the root apices, and severe radiation caries.
      Craniofacial morphology evaluated by cephalometric analysis and dental models
      showed deficiency with mandibular and maxillary hypoplasia.

PMID- 9768419
TI  - Gingival fibromatosis with prune-belly syndrome.
AB  - A case is described in which a child appeared for evaluation with marked gingival
      overgrowth, facial dysmorphism, and abdominal defects consistent with prune-belly
      syndrome. The relationship between this case and other reports of gingival
      enlargement are discussed. Coincidence of the oral, facial, and abdominal
      abnormalities has not been previously reported.

PMID- 9768420
TI  - Caliber-persistent labial artery. A common vascular anomaly.
AB  - Sixteen cases of caliber-persistent labial artery of the lips have been reported
      to date in the English literature. Six of these were clinically misdiagnosed as
      squamous cell carcinoma and treated with wedge resection. To date, we have seen
      187 cases clinically and an additional 23 cases through our surgical oral
      pathology services. Careful clinical observation usually reveals a soft linear or
      papular bluish elevation above the labial mucosal surface. The unique feature is
      pulsation--not simply pulsation toward and away from the observer, which can be
      caused by an underlying artery, but lateral pulsation, which only an artery can
      exhibit. All but 2 of our 187 clinical cases were asymptomatic. To the best of
      our knowledge, this is the first report of caliber-persistent labial artery of
      the upper lip. The upper:lower lip ratio for the clinical cases was almost 2:1.
      Three times as many lower lip as upper lip lesions were biopsied. Males and
      females were almost equally affected (clinical cases, 76:86; histopathologic
      cases, 9:13). Although a vascular term (artery, hemangioma, phlebolith, varix,
      vascular malformation) was used on the biopsy form in one half of the clinical
      differential diagnoses, none of the clinical histories mentioned pulsation. In
      contrast to the cases of Miko et al. in 1980 and 1983, none of our cases
      manifested itself as an ulcer, nor was carcinoma ever mentioned in the clinical
      differential diagnosis. The purpose of this article is to familiarize clinicians
      and pathologists with the clinical and histopathologic features of this seldom
      reported but common vascular anomaly. Clinicians should carefully look for
      lateral pulsation in lip mucosal papules so as to avoid unnecessary surgery and
      intraoperative arterial bleeding. Pathologists should recognize that a relatively
      large-caliber superficial artery in a lip biopsy may not be an incidental finding
      but rather the clinical lesion that was biopsied.

PMID- 9768421
TI  - Adenomatoid dentinoma. Report of four cases of an unusual odontogenic lesion.
AB  - Four cases of a rare odontogenic lesion are reported. In each of the 4 examples,
      the lesion manifested itself as a well-circumscribed unilocular radiolucency in
      the mandibular third molar region in an adult. The histopathologic features
      consisted of an encapsulated proliferation of odontogenic hard and soft tissues.
      The hard tissue component consisted of dentin deposited in a peripheral ringlike
      configuration that enclosed odontogenic epithelium resembling adenomatoid
      odontogenic tumor. Whether this process represents a neoplasm or an odontogenic
      hamartoma is an unresolved question. Treatment in each case consisted of
      curettage, and no recurrences were observed.

PMID- 9768422
TI  - Oral verrucous carcinoma. Incidence in two US populations.
AB  - Much is known about the clinical appearance, biological behavior, and treatment
      of verrucous carcinoma of the oral cavity. However, the epidemiologic
      characteristics are completely unknown. This cancer is considered to be rare in
      Western cultures because it is not common in oral pathology biopsy services, but
      there is no epidemiologic evidence for this belief. To provide this evidence, 2
      population-based incidence investigations were carried out, one in Rochester,
      Minn., and the other in the state of West Virginia. The results were as follows:
      the age-adjusted average annual incidence rate for oral verrucous carcinoma among
      Rochester residents was 0.1/100,000 person-years (0.2 for males, 0.0 for
      females), whereas the incidence rate for all intraoral carcinomas was 3.6/100,000
      person-years (5.4 for males, 2.1 for females). Among men over 64 years of age,
      the incidence rate for verrucous carcinoma was increased to 3.2/100,000 person
      years. Verrucous carcinoma was among the least common of the oral carcinomas in
      this population, representing only 3% of the total. The age-adjusted incidence
      rate for oral and pharyngeal verrucous carcinoma among West Virginia residents
      was somewhat greater, 0.3/100,000 person-years, and showed an even gender
      predilection (0.28 for males, 0.29 for females). The incidence rate for all
      oral/pharyngeal cancers in West Virginia was 8.8/100,000 person-years (13.4 for
      males, 5.7 for females), which was below the US average. The conclusion is that
      oral verrucous carcinoma is a rare tumor of older people, diagnosed in only 1 to
      3 of every 1,000,000 persons each year.

PMID- 9768423
TI  - Radiotherapy for cancer of the lip. A long-term evaluation of 85 treated cases.
AB  - The results of radiation therapy, both as a single treatment modality and after
      radical surgery for squamous cell carcinoma of the vermilion surface/border of
      the lip, are retrospectively analyzed in 85 patients. All recurrences (7%)
      occurred in T2 and T3 tumors treated with external beam radiotherapy only. The
      long-term esthetic result and functional morbidity are evaluated. Referral
      patterns are discussed, and the need for a multidisciplinary treatment protocol
      is emphasized.

PMID- 9768424
TI  - Status of the specialty of oral and maxillofacial pathology, 1997.

PMID- 9768425
TI  - Nonsurgical root canal therapy treatment with apparent indications for root-end
      surgery.
AB  - The recent introduction of the surgical microscope to the practice of
      endodontics, especially for surgery, has allowed clearer visualization of the
      periapex during root-end resection and filling. However, despite this and other
      technologic advances, it has not been demonstrated that in the absence of
      thorough canal debridement the success rate of periapical surgery has improved
      over the 50% to 60% demonstrated in most long-term prognosis studies. Therefore
      it remains important to fully instrument and obturate the root canal system with
      conventional therapy before surgery is considered; this considerably improves the
      long-term prognosis. Each of the case reports in this article involves a
      situation in which conventional treatment was performed when a surgical approach
      might have been considered as the treatment of choice. Surgery should not be
      considered to be the primary treatment when root canal treatment or retreatment
      may be readily achieved. Indeed, the operating microscope and other technical
      aids will probably allow more cases to be treated and retreated conventionally
      that might otherwise have required surgical intervention.

PMID- 9768426
TI  - Morphologic effects on L929 fibroblasts of titanium tetrafluoride application.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of titanium
      tetrafluoride solution on L929 fibroblasts by scanning electron microscopy.
      Titanium tetrafluoride was then compared with sodium fluoride and acidulated
      phosphate fluoride. STUDY DESIGN: Cells were treated with fluoride solutions for
      1 minute either directly, through a filter membrane with a pore size of 0.4
      micron, or indirectly, through dentin disks; they were then investigated at an
      electron microscopic level. RESULTS: Fluoride application on smeared dentin disks
      showed fewer cytotoxic effects on fibroblasts than application on nonsmeared
      dentin disks. Acidulated phosphate fluoride and titanium tetrafluoride appeared
      to be more cytotoxic than sodium fluoride. Because all fluoride solutions used in
      this study contained the same fluoride concentration, pH was considered to be the
      main factor causing the higher toxicity. CONCLUSION: Because these solutions
      demonstrated toxicity in vitro, they must be further evaluated under in vivo
      conditions to ascertain their clinical safety.

PMID- 9768427
TI  - Dens invaginatus. Review of formation and morphology with 2 case reports.
AB  - Dens invaginatus manifests itself with an aberrant morphologic character because
      of altered patterns of tooth formation. Presented in this article are 2 cases of
      dens invaginatus in maxillary lateral incisors that were successfully treated
      nonsurgically. In the first case, a circular main canal was clearly observed
      surrounding the invaginated canal. The involved tooth in the second case
      responded to electric pulp testing, though a periapical radiolucency was evident;
      root canal treatment of the invaginated canal failed to resolve the pathosis.
      Debridement of both the main canal and the invaginated canal produced resolution.
      The complex morphologic nature of these root canal systems and the close
      relationship between the invaginated and main canals is demonstrated and
      discussed.

PMID- 9768428
TI  - A study of the impact of screening or selective radiography on the treatment and
      postdelivery outcome for edentulous patients.
AB  - OBJECTIVE: The purpose of this study was to assess the impact of radiographic
      findings on complete denture treatment and on the postdelivery course of those
      patients who had pretreatment radiographs (the screening group) and those who did
      not (the selection group). METHOD: In total, 375 cases were randomly selected by
      systematic sampling. Data collected included patient demographic information and
      denture history, predenture fabrication radiographic findings, and postdenture
      delivery complaints. RESULTS: Of the screening patients, 100% had pretreatment
      radiographs made; this compared with 13.5% of the selection patients. In the
      screening group, 68.3% of patients had one or more positive radiographic findings
      recorded. Of the screening patients, 8.3% received treatment before denture
      fabrication; this compared with 1.2% of the selection patients. Of the 375 cases,
      2 screening patients had postdelivery complaints that required management other
      than denture adjustment. CONCLUSION: The results indicate that there is weak
      scientific support for the guideline recommending routine pretreatment
      radiography for new denture patients.

PMID- 9768429
TI  - Landmark identification error in submentovertex cephalometrics. A computerized
      method for determining the condylar long axis.
AB  - The purpose of this study was to examine the identification error of certain
      submentovertex landmarks and to compare three different methods of determining
      horizontal condylar angulation in submentovertex radiographs. To determine
      landmark identification error, a random sampling of 12 submentovertex radiographs
      from preorthodontic patients between the ages of 10 and 17 years was used to
      determine both intraexaminer and interexaminer reliability. The error associated
      with the identification of each of 11 landmarks varied between specific
      landmarks, between the same landmarks bilaterally, and between the vertical and
      horizontal components of the same landmark. In general, intraexaminer data showed
      less landmark identification error in both vertical and horizontal directions
      than did interexaminer data. The foramen spinosum landmarks demonstrated the
      lowest identification error in both horizontal and vertical direction
      (intraexaminer), whereas greater identification error was associated with the
      condylar lateral poles and posterior condylar points (both intraexaminer and
      interexaminer). A comparison of three different methods of condylar angulation
      determination was undertaken through the use of two tracings of each of 101
      submentovertex radiographs. A computer-derived method representing the principal
      axis of minimum moment of inertia of the condyle was shown to be more reliable (p
      < 0.05) with respect to describing condylar angulation than both a method that
      used a best-fit line through the anterior condylar border and an interpolar axis
      method.

PMID- 9768430
TI  - A reliability comparison of submentovertex and zonographic methods of horizontal
      condylar angle estimation.
AB  - OBJECTIVE: The objectives of this retrospective clinical study were, first, to
      compare submentovertex radiography and zonographic temporomandibular joint
      orientation programs that use the Scanora imaging system with respect to the
      reproducibility with which the angulation of the horizontal condylar axis may be
      determined and, second, to assess the level of agreement between the 2 methods.
      STUDY DESIGN: Submentovertex radiographs and zonographic projections of 16 joints
      (8 patients) were evaluated. Two raters independently determined the horizontal
      angulation of each condyle 3 times using each method. Horizontal condylar angle
      measurements differing by no more than 5 degrees were considered to be in
      agreement. Statistical analyses were performed with a repeated-measures analysis
      of variance, sign tests, and Wilcoxon signed rank test. RESULTS: No significant
      difference was found in the 3 measurements between the 2 raters (P = .9122) or
      between the raters adjusted for method (P = .5093). A significant difference was
      found between methods (P = .0001). Intrarater agreement values were 81% and 88%
      for the submentovertex method and 75% for each rater for the zonographic method.
      Interrater agreement was 94% for each method. Intermethod agreement was 50% for
      one rater and 81% for the other. CONCLUSIONS: The submentovertex and zonographic
      methods of determining the horizontal condylar angulation demonstrated
      consistency and reliability both within and between the raters. However, the
      zonographic method did not agree with the submentovertex method. This findings
      does not imply that the zonographic is not a clinically acceptable technique for
      the determination of the horizontal condylar angulation when subsequent
      tomographic projections are made on the same unit with the same head-positioning
      device.

PMID- 9768431
TI  - Gross periostitis ossificans in mandibular osteomyelitis. Review of the English
      literature and radiographic variation.
AB  - OBJECTIVE: The purpose of this study was to describe a radiographic variety of
      gross periostitis ossificans in mandibular osteomyelitis and to determine what
      types of gross periostitis ossificans are related to a specific form of
      mandibular osteomyelitis without demonstrable causes. STUDY DESIGN: We reviewed
      20 cases of gross periostitis ossificans in patients with mandibular
      osteomyelitis that had been reported with illustrations in the English
      literature, and we reviewed our own 14 cases of gross periostitis ossificans,
      previously reported. The radiographic features of the 34 cases of gross
      periostitis ossificans were classified according to the status of original
      contour and the appearance of gross periostitis ossificans. Histopathologic
      features were studied in 12 cases. RESULTS: The 34 cases of gross periostitis
      ossificans could be classified radiographically into 4 types. Type A, showing an
      "onion-skin" appearance, was caused by a carious tooth or followed extraction of
      a tooth. Type B and type C showed a consolidation form; in the 36.8% (7/19) of
      these cases in which no infectious source could be identified, it was suspected
      that the condition was caused by a developing unerupted tooth or a dental
      follicle. Type D was seen in the most chronic stage. Biopsy specimens of 12 cases
      commonly showed proliferation of newly formed bone, loose interstitial fibrous
      tissue, and a low-grade inflammatory cell infiltration. CONCLUSION: Gross
      periostitis ossificans of type B or type C may be a specific form of mandibular
      osteomyelitis without demonstrable cause.

PMID- 9768432
TI  - Acute renal failure--which treatment modality is the best?
AB  - Despite the progress in animal research concerning the pathophysiology and the
      progress in clinical practice regarding the methods of therapy, the incidence and
      mortality of acute renal failure remain high, especially when other organs are
      involved. New pharmacological interventions have led to the perspective that in
      the near future it may be possible to prevent and/or ameliorate this devastating
      syndrome. Continuous dialysis therapy and the selection of a biocompatible
      membrane may possibly help the critically ill patient especially when parenteral
      nutrition and correction of electrolyte and acid-base disturbances are important.
      Nevertheless, more solid data are needed and one should take into consideration
      that acute renal failure is a multifactorial syndrome. The type of dialysis
      itself is not the only matter which has to be evaluated since the mortality rate
      can be correlated with the number of involved organs before or after the
      initiation of acute renal failure and with the severity of the original disease.
      In clinical practice, a large number of prospective studies and more
      sophisticated statistical methodology are needed in order to evaluate the proper
      treatment modality.

PMID- 9768433
TI  - Vascular contributions to pathogenesis of acute renal failure.

PMID- 9768434
TI  - Proteases in renal cell death: calpains mediate cell death produced by diverse
      toxicants.
AB  - The role of proteases in renal cell death has received limited investigation.
      Calpains are non-lysosomal cysteine proteases that are Ca+2 activated. Calpain
      inhibitors that block the active site of calpains (calpain inhibitor 1 and 2) or
      the Ca+2 binding domain of calpains (PD150606) decreased calpain activity in
      rabbit renal proximal tubule (RPT) suspensions. The inhibition of calpain
      activity decreased cell death produced by the diverse toxicants antimycin A
      (mitochondrial inhibitor), tetrafluroethyl-L-cysteine (nephrotoxic halocarbon),
      bromohydroquinone (nephro-toxic quinone), t-butylhydroperoxide (model oxidant)
      and ionomycin (Ca+2 ionophore). In summary, calpains appear to play a common and
      critical role in cell injury produced by diverse toxicants with different
      mechanisms of action. The general cysteine protease inhibitor trans-epoxysuccinyl
      L-leucylamido (4-guanidino)-butane (E-64) decreased antimycin A- and
      tetrafluoroethyl-L-cysteine-induced cell death but had no effect on
      bromohydroquinone- or t-butylhydroperoxide-induced cell death. Serine/cysteine
      protease inhibitors (antipain, leupeptin) were not cytoprotective to RPT exposed
      to any of the toxicants. The cytoprotection associated with E-64 correlated with
      inhibition of lysosomal cathepsins and E-64 was only cytoprotective after some
      cell death had occurred. Since some cell death occurred prior to the E-64
      cytoprotective effect, lysosomal cathepsins may be released from dying cells and
      subsequently target the remaining viable cells.

PMID- 9768435
TI  - The nephrotoxicity of new and old immunosuppressive drugs.
AB  - The above snapshot of the relevant literature on chronic Cyclosporine and
      Tacrolimus nephropathy indicate fertile areas for further study. The reader is
      referred to recent reviews for a more in-depth analysis of this problem (2).

PMID- 9768436
TI  - Update on clinical trials with atrial natriuretic peptide in acute tubular
      necrosis.

PMID- 9768437
TI  - The roles of apoptosis in uranyl acetate-induced acute renal failure.

PMID- 9768438
TI  - Early glomerular effects of contrast media in rats: evaluation with a simple
      method.
AB  - The aim of this study was to evaluate the early effects of high and low-osmolar
      contrast media on glomerular function in rats by using a new method based on the
      measurement of the urinary excretion of 99mTc-DTPA. Thirty-six Sprague-Dawley
      male rats were examined: nine rats were injected with diatrizoate (ionic high
      osmolar contrast medium), nine rats with iohexol (nonionic low-osmolar contrast
      medium), and nine rats with saline as controls. The urinary excretion of 99mTc
      DTPA in the first minutes after i.v. injection was assumed as an index of
      glomerular filtration rate. A lower urinary excretion of 99mTc-DTPA was found in
      rats treated with contrast media in comparison with control rats. This effect was
      more evident after diatrizoate but was statistically significant also after
      iohexol. In conclusion, a reduction in the glomerular filtration rate probably
      occurs in the first few minutes after contrast media administration. The
      measurement of urinary excretion of 99mTc-DTPA could be a simple method to detect
      acute glomerular effects due to contrast media or to other drugs.

PMID- 9768439
TI  - Urinary excretion of proteins and tubular enzymes in renal transplant patients.
AB  - The aim of this study was to evaluate, in renal transplant recipients with
      different function of the graft, the urinary excretion of some low molecular
      weight proteins and tubular enzymes frequently employed as indicators of tubular
      dysfunction. Urinary excretion of proteins and enzymes was measured in 51 renal
      transplant patients and, for comparison, in 73 patients affected by different
      kidney diseases with various degrees of renal function. Values of urinary beta 2
      microglobulin and retinol-binding protein higher than normal were found in most
      transplanted patients, even in those with good renal function. On the other hand,
      in renal patients the urinary excretion of low molecular weight proteins was high
      only when creatinine clearance was lower than 30 mL/min/1.73 m2. Furthermore, an
      increased urinary excretion of tubular enzymes was found in a higher number of
      transplanted patients than of renal patients. This behavior was particularly
      evident for lysosomal enzyme N-acetyl-beta-D-glucosaminidase. In conclusion, a
      tubular dysfunction occurs in the transplanted kidneys, even in those with well
      preserved glomerular function.

PMID- 9768440
TI  - Atrial natriuretic peptide as a preload depressor in acute renal failure
      secondary to congestive heart failure.
AB  - The present study was undertaken to verify the hypothesis that infusion of atrial
      natriuretic peptide (ANP) might lower preload and be beneficial in the treatment
      of pulmonary congestion even without a diuresis in patients with acute renal
      failure (ARF) secondary to severe congestive heart failure (CHF). We studied 22
      patients with ARF secondary to CHF. The mean age of the patients (14 men and 8
      women) was 72 years (range 36 to 85 years). Seven of the patients had dilated
      cardiomyopathy, ten had ischemic heart disease, and five had valvular heart
      disease. ANP was infused intravenously and the following data before and 1 hour
      after the start of ANP infusion were recorded; urinary output, systemic blood
      pressure (SBP), pulmonary blood pressure (PBP), right atrial pressure (RAP),
      cardiac index (CI), heart rate (HR), and arterial blood oxygen partial pressure.
      Diastolic PBP were employed as pulmonary capillary wedge pressure. Urinary output
      did not change. Mean SBP decreased from 92 to 85 mmHg (p < 0.05), and mean PBP
      decreased from 34 to 28 mmHg (p < 0.01). Mean RAP decreased from 11 to 9 mmHg (p
      < 0.01) and diastolic PBP decreased from 25 to 19 mmHg (p < 0.01). HR did not
      change significantly and CI increased 2.4 to 2.5 mi/min/m2 (p < 0.05). Arterial
      blood oxygen partial pressure increased significantly from 71 to 82 mmHg (p <
      0.05). In conclusion, ANP decreased preload and improved arterial blood oxygen
      partial pressure, though diuretic response to ANP is attenuated in ARF secondary
      to CHE. Infusion of ANP will be very beneficial in cases in which dyspnea and
      pulmonary edema due to elevation of preload are the principal clinical problems.

PMID- 9768441
TI  - Prognosis in acute renal failure of septic origin: a multivariate analysis.
AB  - The goal of the present study was to identify variables associated with the
      outcome of patients with acute renal failure (ARF) of septic origin, using
      multivariate analysis. The records of 168 patients were reviewed retrospectively
      and a crude mortality of 74% was found. Both univariate as well as multivariate
      analysis demonstrated an association between mortality and variables which
      depended on patient related factors. These included age over 60 years and several
      underlying diseases such as pneumonia, peritonitis, and organ dysfunction. Only
      one variable (late oliguria) related to the ARF itself. Thus, outcome seems
      related to underlying disease more than to severity of ARF.

PMID- 9768442
TI  - Normotensive scleroderma renal crisis: case report and review of the literature.
AB  - A 58 year old man presented with skin manifestations of scleroderma without
      systemic involvement. Within few weeks of oral corticosteroids and penicillamine
      therapy, rapidly progressive systemic sclerosis developed. The deterioration
      manifested by skin lesions, diffuse interstitial restrictive lung disease, acute
      renal failure with normal blood pressure values, and microangiopathic hemolytic
      anemia compatible with hemolytic uremic syndrome. Chronic renal failure developed
      and was treated by dialysis, but the patient died due to sepsis. The course of
      renal involvement was normotensive; antihypertensive therapy was not prescribed
      even once. The association of scleroderma renal crisis with normal blood pressure
      is probably a rare and ominous combination.

PMID- 9768443
TI  - A case of microscopic polyarteritis nodosa with interstitial pneumonia
      successfully treated with steroid pulse therapy and immunosuppressive agents.
AB  - We report a patient with microscopic polyarteritis nodosa (mPN) and interstitial
      pneumonia, who was subjected to investigation by bronchoalveolar lavage (BAL),
      thoracic computerized tomography (CT) and gallium-67 citrate (67Ga) scintigraphy
      before and after administration of glucocorticoid and immunosuppressive agents.
      Renal function, renal histology, interstitial inflammation of the lung, and
      pulmonary function and histology improved cytoplasmic autoantibody (MPO-ANCA),
      which decreased with decreasing disease activity after starting treatment.
      Interstitial pneumonia may be associated with pulmonary capillaritis due to mPN.
      Methylprednisolone pulse therapy followed by oral prednisolone and
      immunosuppressive agents is considered to be an effective therapeutic strategy
      for combined mPN and interstitial pneumonia.

PMID- 9768444
TI  - Perinatal determinants of adult cardiovascular disease and cancer.
AB  - Interest in perinatal factors, especially birthweight, as determinants of adult
      onset diseases has been steadily growing. Low birthweight has been associated
      with increased risk of cardiovascular disease, and high birthweight has been
      linked to higher risk of breast and possibly other cancers. Most mechanistic
      hypotheses that have been advanced to explain the empirical evidence linking
      perinatal conditions to adult-life disease in humans have invoked modulation of
      physiological processes by exogenous factors or poorly specified "programming"
      during fetal life. A form of programming that has a strong biological foundation
      and has recently been suggested for further study is genomic imprinting, which
      involves non-permanent DNA modifications and allows for influences that span
      three generations. The subject of the perinatal origin of adult-onset disease has
      profound implications and a large and reliable body of evidence needs to be
      assembled for biological theories to be validly evaluated against.

PMID- 9768445
TI  - Use of a historical register in social epidemiology: child mortality in Stockholm
      at the turn of the 19th century.
AB  - This study describes the age- and cause-specific levels and social determinants
      of high child mortality in Stockholm around the turn of the century. The study is
      based on computerized individual level sociodemographic information and the death
      certificates of children aged 0-15 years residing in Maria parish in Stockholm
      during the years 1885, 1891 and 1910 (n = 36,718) from a historical register (the
      Roteman archives). The usefulness of such data for further studies in social
      epidemiology is discussed. Age-specific rates and major causes of death compared
      well with other studies. Low social class and being born out of wedlock increased
      the overall risk of death in early childhood. Data appear valid and may be useful
      in social epidemiology. Further analyses of data from the Roteman archives may
      contribute to the understanding of causes behind high levels of cause- specific
      child mortality and trends in mortality in relation to societal change.

PMID- 9768446
TI  - Review of social epidemiologic research on migrants' health: findings,
      methodological cautions, and theoretical perspectives.
AB  - The phenomenon of world-wide immigration and migration has major implications for
      the health of the migrants in addition to its impact upon social and other
      service providers. Studies of migrants that utilize social epidemiologic methods
      fall within the traditional boundaries of descriptive and analytic approaches;
      this article reviews some of the studies that exemplify these approaches. It then
      suggests specific methodological issues and cautions pertaining to research on
      migrants and provides a theoretical model for organizing the diverse research
      studies that have been conducted. By stimulating discussion regarding social
      epidemiologic research on migrants' health, this model is intended to serve as a
      compass point for future research and needed interventions.

PMID- 9768447
TI  - Planning a worksite health promotion program: health profile of a population of
      Greek sailors.

PMID- 9768448
TI  - Tobacco use and exposure to environmental tobacco smoke in relation to certain
      work characteristics.
AB  - This study aims to describe the prevalence of smoking, snuff use, and exposure to
      environmental tobacco smoke (ETS) in relation to occupation among common female
      and male workers in Sweden. The associations between shift work, job strain, and
      tobacco use and exposure to ETS are assessed. The results are based on
      questionnaire data of 2,584 men and 2,836 women randomly selected from 63
      occupations in two counties in Sweden. The prevalence of smoking ranges from 10%
      (95% CI 4.5-16%, police officers) to 42% (95% CI 29-55%, packing workers) in men,
      and between 8% (95% CI 2-14%, dentists) and 51% (95% CI 37-65%, packing workers)
      in women. Snuff use is more common among men (range 11-44% in different
      occupations) than among women (range 0-7%). The prevalence of exposure to passive
      smoking in this study ranges from 0.9% to 26% in men and from 0% to 30% in women.
      Shiftwork is significantly associated with current smoking, and job strain is
      significantly related to exposure to ETS. Ages between 18 and 29 years
      experienced an increased risk of exposure to ETS compared to older age groups. In
      conclusion, this study shows that tobacco use and exposure to ETS is still a
      major problem in the Swedish workplace.

PMID- 9768449
TI  - Differences in injury mortality between the Nordic countries--with special
      reference to differences in coding practices.
AB  - The aims of the study are to analyse the incidence and patterns in injury
      mortality in the Nordic countries, and to assess the extent to which any
      differences found can be explained in terms of either variation in statistical
      validity or the existence of genuine differences. The study considers the entire
      injury panorama, and is performed between certain categories of injuries.
      Analysis is applied to all ages, and also to certain specific age categories.
      Finland appears as the Nordic country with the highest injury mortality. While
      examining potential source of errors, nothing was found to merit an adjustment of
      Finland's rate. All potential correction would bring the rates of the other
      Nordic countries closer to that of Finland. Poisoning was found to be a diagnosis
      that varies in application between the Nordic countries. Falling is the diagnosis
      with the greatest problems of sensitivity, and cannot be recommended for
      comparative purposes.

PMID- 9768450
TI  - Prevalence of intellectual dysfunctioning and its correlates in a community
      residing elderly population.
AB  - To examine the prevalence of intellectual dysfunctioning and its correlates in
      community-residing elderly people, a randomly selected sample of 1,405 people
      aged 65 and over living in Settsu, Osaka, were investigated in October 1992. Data
      for assessing intellectual dysfunctioning were obtained from 1,364 people
      (97.1%), excluding 21 clinically demented people (1.5%); 17.6/100, 5.6/100, and
      3.3/100 of the population showed minor, moderate, and appreciable intellectual
      dysfunctioning, respectively, and the prevalence of intellectual dysfunctioning
      increased with age. By multivariate analyses using logistic regression, age over
      75, poor general health, including current medical treatment, and psychosocial
      conditions such as no participation in social activities, no life worth living
      (no Ikigai), and anxiety about the future were independent risk factors for
      intellectual dysfunctioning. We conclude that intellectual dysfunctioning is
      closely associated with health and psychosocial conditions.

PMID- 9768451
TI  - Gender trends in sick-listing with musculoskeletal symptoms in a Swedish county
      during a period of rapid increase in sickness absence.
AB  - Sickness absence and disability pension due to musculoskeletal diagnoses has
      increased in Sweden. STUDY OBJECTIVE: To study gender trends in sickness absence
      with musculoskeletal diagnoses and its changes in 1985-87. DESIGN: A prospective
      population-based study of all new sick-leave spells exceeding seven days in 1985
      87. Sickness absence with "all diagnoses" was compared to "all musculoskeletal
      diagnoses", the latter group was also divided into three sub-groups. SETTING: The
      county of Ostergotland, Sweden. PARTICIPANTS: All sick-leave insured aged 16-65;
      107,000 women and 100,000 men. RESULTS: More women than men were sick-listed in
      "all diagnoses" in 1985. There were corresponding gender differences in sickness
      absence with musculoskeletal diagnoses except with the diagnosis "low back pain".
      Sick-listing with musculoskeletal diagnoses increased for both women and men from
      1985 to 1987, but the increase was consistently much higher for women, especially
      for younger women.

PMID- 9768452
TI  - Trend of psychological distress in a Swedish population from 1989 to 1995.
AB  - The economic recession which began in Sweden in 1991 was followed by a large
      increase in the unemployment rate, especially in the younger labour force. The
      main purpose of the present study was to examine whether this recession has
      resulted in an increase in psychological distress in the population. Self
      reported symptoms of anxiety, anguish, depression and sleeplessness have been
      analysed in repeated cross-sectional surveys conducted every other year from 1989
      to 1995 in the County of Ostergotland. The study was confined to the 20-39 years
      age group and includes 3122 male and 3440 female respondents. The analysis was
      restricted to symptoms reported as occurring often or constantly. There was a
      significant increase in the 12-month prevalence of psychological distress among
      both men and women. At the beginning of the period 5% of the men in the 20-29
      years age group reported frequent symptoms of psychological distress. By 1995
      this had increased to 10%. The largest increase in prevalence, however, was found
      in men in the 30-39 years age group and women in the 20-29 years group
      Interestingly, when the non-employed groups were excluded from the analysis, the
      increasing trends of reported distress remained statistically significant with
      the exception of women aged 30-39 years.

PMID- 9768453
TI  - Self-rated health among cardiovascular drug users in a study of Swedish twins.
AB  - The aim of this study was to analyse the relationship between self-perceived
      health and cardiovascular disease with and without drug treatment. Mental health
      and genetic effects were controlled for in the analyses. The data for these
      analyses were collected in 1984 as part of the Swedish Adoption/Twin Study of
      Aging (SATSA). In the first set of analyses, 1147 persons (mean age 60 years, 72%
      older than 50 years) were included. In the second part of the study, twin pairs
      discordant with respect to having a cardiovascular disease and/or drug use were
      included in the analyses. Cardiovascular disease was related to poor, self-rated
      health among both men and women. The proportion with bad health was largest among
      those with a drug-treated disease. In multivariate analyses, a strong
      relationship between cardiovascular disease, drug therapy and low self-rated
      health remained after controlling for mental health. The co-twin control analyses
      indicate that cardiovascular drugs have at most a marginal negative effect on
      health beyond the effects of the disease and genetic liability to self-perceived
      poor health.

PMID- 9768454
TI  - Doctors' attitudes to fibromyalgia: a phenomenological study.
AB  - Besides specific technical skills, successful encounters with patients require an
      understanding of the many ways in which patients may express themselves. This
      qualitative study reports on the clinical experiences of doctors when meeting
      patients with fibromyalgia (FM). Ten strategically chosen rheumatologists and 10
      GPs in central Sweden were interviewed. The interviews were taped, transcribed
      and analysed in accordance with the empirical, phenomenological, psychological
      method. The analyses indicate that doctors try to comply with the wishes and
      demands of patients, and at the same time avoid perceptions of personal
      frustration. They are inclined to be objective and to act instrumentally,
      apparently in order to keep in touch with what gave biomedical meaning to an
      otherwise incomprehensible phenomenon. The meaning structures revealed by
      doctors' descriptions of FM and of relating to FM patients were characterized
      mainly by the way in which the doctors were (i) managing their clinical
      uncertainty, (ii) adhering to the biomedical paradigm, (iii) prioritizing
      diagnostics, (iv) establishing an instrumental relationship, and (v) avoiding
      recognizing FM as a possible biomedical anomaly.

PMID- 9768455
TI  - To sing in a choir and be healthy--which are the mediating mechanisms?

PMID- 9768456
TI  - Tooth wear and temporomandibular joint morphology in a skull material from the
      17th century.
AB  - Skeletal remnants from the skulls of 69 subjects from the 17th century have been
      studied focusing on TMJ morphology and tooth wear. Several of the skulls were
      damaged and altogether 68 condyles and 28 temporal components of the TMJ, and 97
      dentate jaws could be examined. Tooth wear was extensive and most of the first
      molars in both jaws had lost most of their occlusal morphology. This is
      remarkable with respect to the fact that the great majority of the subjects had
      died before the age of 35 years, according to the age determination performed.
      The TMJs showed frequent remodelling but only rarely deformative changes. The
      frequent observation of a broken up compact bone layer on the condyle was
      interpreted as a post-mortem artefact. The results indicate adaptive response of
      the TMJs to the probably heavy masticatory function but do not support the
      suggested relationship between tooth wear and TMJ osteoarthrosis.

PMID- 9768457
TI  - Caries and periodontal conditions in patients with primary Sjogren's syndrome.
AB  - The present investigation was designed to study caries and periodontal conditions
      in a selected group of patients with primary Sjogren's syndrome (1oSS). Twenty
      one patients, 20 females and 1 male aged 44-75 years (mean 64 years), with
      recently diagnosed 1oSS constituted the study population. As a control group, 21
      patients matched according to sex and age were randomly selected from patients at
      one clinic in the Public Dental Service. Clinical examinations including
      registrations of dental caries, restorations, and periodontal conditions were
      performed. Unstimulated and stimulated salivary secretion rates were recorded.
      The 1oSS group had a mean number of 16.4 +/- 8.9 and the control group 17.1 +/-
      8.4 natural teeth. The 1oSS patients had significantly more DF crown surfaces (63
      +/- 25.8 vs 43 +/- 21.3) and more inactive root caries (4.4 +/- 5.4 vs 0.5 +/-
      0.9) than did the control patients. No significant differences were found between
      the groups in the periodontal conditions. The mean value of the unstimulated
      salivary secretion rate was 0.09 +/- 0.16 ml/15 min in the 1oSS group and 3.33 +/
      2.81 ml/15 min in the control group. The stimulated secretion rate was 0.16 +/-
      0.15 ml/min and 1.47 +/- 0.64 ml/min respectively. This study confirms results
      from other studies that patients with 1oSS face a high risk of developing both
      coronal and root caries due to xerostomia. The periodontal conditions are similar
      to those found in patient groups in general dentistry.

PMID- 9768458
TI  - Atopic dermatitis, conjunctivitis, and hand dermatitis among Swedish dental
      personnel, including use of personal protective devices.
AB  - A previous study on dental personnel in northern Sweden show that dentists had a
      significantly higher prevalence of self-reported and physician-diagnosed atopic
      dermatitis and conjunctivitis, compared to chair assistants and referents
      (Lonnroth & Shahnavaz 1998). Further, significantly more male dentists reported
      experience of hand dermatitis compared to male referents. To compare the
      prevalence among dental personnel working in other geographical areas of Sweden,
      and survey the use of personal protective equipment, a questionnaire study was
      conducted during 1997, which included all dentists and his/her chair assistants,
      working in general private and public dental care in Sweden. A total of 7384
      dental personnel were included in the study, 4293 dentists (54.7% male and 45.3%
      female), and 3090 chair assistants. Logistic regression was used for analysing
      data. Results show that significantly more dentists reported symptoms of atopic
      dermatitis, conjunctivitis, and hand dermatitis, and had been diagnosed by a
      physician, compared to chair assistants. However, they did not report more sick
      leave due to symptoms, compared to chair assistants. More female used protective
      devices, than male, and more chair assistants than dentists. Significantly more
      dental personnel in public dental care used protective devices, than in private
      dental care. Use of gloves, and face mask, decreased with increasing age but, use
      of eye protection, mainly in form of prescription spectacles, increased. The
      prevalence of hand dermatitis decreased significantly with increasing age but,
      more for female (p < 0.0001), than for male (p = 0.01).

PMID- 9768459
TI  - Orthodontic aspects on feeding of young children. 1. A comparison between Swedish
      and Norwegian-Sami children.
AB  - 1-18 months old Norwegian-Sami girls from Karasjok/Katokeino were compared with
      girls from Falkoping in Sweden. All Karasjok/Kautokeino children were breastfed,
      usually until 1 year of age. Only a few developed a dummy- or fingersucking
      habit. They started eating porridge at 4-5 months of age. At about half a year of
      age they were fed dark, hard chewing bread to gnaw at. Cut and pulped adult food
      was introduced during the end of the first year of life. In almost all cases the
      children had dried reindeer meat to gnaw at. They were mostly fed by spoon and
      drank from a cup. The Falkoping girls, on the other hand, were not so often
      breastfed and for a shorter time. They usually became dummysuckers. The Falkoping
      girls got almost all their nutrition during the first one or two years by sucking
      or eating food with little chewing resistance. The differences in sucking and
      chewing behavior could influence on the transversal development of the jaws.

PMID- 9768460
TI  - A clinical evaluation of long term retention with bonded retainers made from
      multi-strand wires.
AB  - The majority of patients from 4 orthodontic clinics in the south west of Sweden
      who have had bonded retainers on upper or lower anterior teeth for a period of at
      least 5 years were examined. The total failure rate during 5 years of observation
      was 36 per cent, slightly higher in the maxilla than in the mandible. The
      retainer had become detached in 15 per cent of the teeth bonded. The failure rate
      decreased during the 5 year period of observation. Seven fractures were reported,
      all in the upper front teeth. The failure rate was reduced when the retainers
      were positioned incisally, when larger diameter wires were used and in the 12
      cases where a groove had been cut into the enamel to accept the retainer. The
      findings suggest that a limited flexibility of the retainer may be an advantage.
      In about 20 per cent of the retained segments minor rotations and small areas of
      space opened between some of the teeth attached to the retainer. No new caries
      lesions were found on any of the teeth associated with the bonded retainers
      during the period of observation.

PMID- 9768461
TI  - Introduction to impulsive aggression.

PMID- 9768462
TI  - Defining, measuring, and predicting impulsive aggression: a heuristic model.
AB  - Aggression research does not lack data--it lacks a model for integrating data.
      One of the problems confronting aggression researchers is the extensive body of
      multidisciplinary data that is difficult to synthesize to generate new directions
      in research. This paper proposes one solution that starts by asking "what is the
      minimal number of categories of concepts and measurements which are necessary to
      describe a person?". The answer is four categories of concepts: biological;
      cognitive; behavioral; environmental (physical and social). One way of many for
      integrating these four categories of concepts is a proposed discipline neutral
      heuristic model that is used herein to compare two different research approaches
      to the study of impulsive aggression. This comparison identifies clearly the
      differences in the two approaches with regard to different emphases among the
      four categories of constructs for each program. Using the model an example of
      common ground between the two approaches is sought as a basis for extending
      aggression research. The main conclusion of one of the research programs was that
      central nervous arousal is related to impulsive aggression. This program
      demonstrated that phenytoin will reduce impulsive aggressive acts and has an
      effect on CNS arousal. The other research program on impulsive aggression has
      been at the forefront in demonstrating the well established inverse relationship
      between serotonin levels and aggression. The comparison resulted in the
      suggestion that both serotonin and phenytoin may relate to a common neurochemical
      substrate which interacts in part to control CNS arousal, especially at the
      cortical level. The proposed heuristic model made obvious the need to use
      synthesizing concepts (e.g. information processing or language) which can
      interrelate multidisciplinary concepts and data from different research programs
      within the four categories of constructs when comparing interdisciplinary
      research.

PMID- 9768463
TI  - Neurobiologic correlates of violence: relevance to criminal responsibility.
AB  - Studies addressing the relationship between neurotransmitter functioning and
      violent crime are reviewed. A rich literature exists to support the notion that
      monoamine (i.e., serotonin, dopamine, and norepinephrine) neurotransmitter
      functioning is related to human aggressive behaviour. Results from these studies
      provide, at best, indirect evidence that neurotransmitter abnormalities are
      involved in violent criminal behavior. Few studies have specifically addressed
      the role of neurotransmitter functioning in violent crime. To illustrate how
      current knowledge in this area has been applied in forensic settings, a case
      study in which neurotransmitter functioning was introduced as evidence to support
      an insanity defense is presented. Potential problems associated with such
      defenses are discussed.

PMID- 9768464
TI  - Reduced prefrontal and increased subcortical brain functioning assessed using
      positron emission tomography in predatory and affective murderers.
AB  - There appear to be no brain imaging studies investigating which brain mechanisms
      subserve affective, impulsive violence versus planned, predatory violence. It was
      hypothesized that affectively violent offenders would have lower prefrontal
      activity, higher subcortical activity, and reduced prefrontal/subcortical ratios
      relative to controls, while predatory violent offenders would show relatively
      normal brain functioning. Glucose metabolism was assessed using positron emission
      tomography in 41 comparisons, 15 predatory murderers, and nine affective
      murderers in left and right hemisphere prefrontal (medial and lateral) and
      subcortical (amygdala, midbrain, hippocampus, and thalamus) regions. Affective
      murderers relative to comparisons had lower left and right prefrontal
      functioning, higher right hemisphere subcortical functioning, and lower right
      hemisphere prefrontal/subcortical ratios. In contrast, predatory murderers had
      prefrontal functioning that was more equivalent to comparisons, while also having
      excessively high right subcortical activity. Results support the hypothesis that
      emotional, unplanned impulsive murderers are less able to regulate and control
      aggressive impulses generated from subcortical structures due to deficient
      prefrontal regulation. It is hypothesized that excessive subcortical activity
      predisposes to aggressive behaviour, but that while predatory murderers have
      sufficiently good prefrontal functioning to regulate these aggressive impulses,
      the affective murderers lack such prefrontal control over emotion regulation.

PMID- 9768465
TI  - Antisocial personality disorder and psychopathy: diagnostic dilemmas in
      classifying patterns of antisocial behavior in sentencing evaluations.
AB  - Antisocial Personality Disorder (APD) and PCL-R psychopathy are critically
      examined regarding their application to sentencing determinations. PCL-R
      psychopathy is emerging in the literature as a more useful forensic diagnostic
      construct than APD, which appears flawed by multiple weaknesses. These include
      shifting diagnostic criteria, innumeracy problems, absence of symptom weighting,
      temporal instability, and the equivalence of some symptoms with substance abuse
      disorders. Additionally, APD overdiagnosis may result from inattention to issues
      of social context, trauma history, and symptom pervasiveness. Neither objective
      nor projective personality testing reliably differentiates APD. Finally, an APD
      diagnosis does not always indicate criminal, much less incorrigible criminal
      behavior. By contrast, PCL-R psychopathy results are strongly predictive of
      criminal behavior and violent recidivism for Caucasian males through mid-life
      residing in the community. Emerging research with the PCL-R regarding other
      important populations and contexts is promising but generalization is currently
      limited.

PMID- 9768466
TI  - Impulsive corporal punishment by mothers and antisocial behavior and
      impulsiveness of children.
AB  - This study tested the hypothesis that corporal punishment (CP), such as spanking
      or slapping a child for purposes of correcting misbehavior, is associated with
      antisocial behavior (ASB) and impulsiveness by the child. The data were obtained
      through interviews with a probability sample of 933 mothers of children age 2-14
      in two small American cities. Analyses of variance found that the more CP
      experienced by the child, the greater the tendency for the child to engage in ASB
      and to act impulsively. These relationships hold even after controlling for
      family socioeconomic status, the age and sex of the child, nurturance by the
      mother, and the level of noncorporal interventions by the mother. There were also
      significant interaction effects of CP with impulsiveness by the mother. When CP
      was carried out impulsively, it was most strongly related to child impulsiveness
      and ASB; when CP was done when the mother was under control, the relationship to
      child behavior problems was reduced but still present. In view of the fact that
      there is a high risk of losing control when engaged in CP, even by parents who
      are not usually impulsive, and the fact that impulsive CP is so strongly
      associated with child behavior problems, the results of this study suggest that
      CP is an important risk factor for children developing a pattern of impulsive and
      antisocial behavior which, in turn, may contribute to the level of violence and
      other crime in society.

PMID- 9768467
TI  - Legal and ethical duties of the clinician treating a patient who is liable to be
      impulsively violent.
AB  - This paper reviews published tort cases that arose after a patient impulsively
      hurt or killed someone. Plaintiffs alleged breach of the duty to protect
      (Tarasoff) or negligent release from hospital. There are sixteen cases involving
      a variety of facts and diagnoses. As a matter of law courts typically hold that
      impulsive violence is not foreseeable. One jury found a defendant negligent but
      that verdict was ultimately overturned. Statutes on duty to protect do not imply
      a duty to act on the fact patterns of impulsive violence in this sample. The
      author concludes that the ethical duty to do careful clinical work is essentially
      identical to the legal duty to use due care in these cases. The law imposes no
      additional burden on the clinician in these cases.

PMID- 9768468
TI  - Mapping cell wall polysaccharides of living microbial cells using atomic force
      microscopy.
AB  - Functionalized atomic force microscope tips were used to sense specific forces of
      interaction between ligand-receptor pairs and to map the positions of
      polysaccharides on a living microbial cell surface. Gold-coated tips were
      functionalized with concanavalin A using a cross-linker with a spacer arm of 15.6
      A. It was possible to measure the binding force between concanavalin A and mannan
      polymers on the yeast (Saccharomyces cerevisiae) cell surface. This force ranged
      from 75 to 200 pN. The shape of the force curve indicated that the polymers were
      pulled away from the cell surface for a fairly long distance that sometimes
      reached several hundred nanometres. The distribution of mannan on the cell
      surface was mapped by carrying out the force measurement in the force volume mode
      of atomic force microscopy (AFM). During the measurement, the maximum cantilever
      deflection after contact between the tip and the sample was kept constant at 10
      nm using trigger mode to keep the pressing force on the sample surface as gently
      as possible at a force of 180 pN. This regime was used to minimize the non
      specific adhesion between the tip and the cell surface. Specific molecular
      recognition events took place on specific areas of the cell surface that could be
      interpreted as reflecting a non-uniform distribution of mannan on the cell
      surface.

PMID- 9768469
TI  - Understanding intercellular interactions and cell adhesion: lessons from studies
      on protein-metal interactions.
AB  - To understand cell-cell interactions and the interactions of cells to non
      biological materials, studies on binding forces between cellular proteins and
      between proteins and non-biological material such as metal surfaces are
      essential. The adsorption of proteins to solid-water interfaces is a
      multifactorial and a multistep process. First steps are determined by long-range
      interactions where surface properties such as hydrophobicity, distribution of
      charged groups, ion concentrations and pH play important roles. In later steps
      structural rearrangements in the protein molecule and dehydration effects become
      more important making the adsorption process often irreversible. In the following
      we demonstrate that protein A and tubulin have a specific type of interaction to
      metal surfaces probably as an intermediate step in the adsorption process. The
      proteins were attached to the tip of a microfabricated cantilever in such a way
      that only one molecule interacts with the surface. By recording force-distance
      curves with an atomic force microscope the adhesion forces of single molecules
      binding to gold, titanium and indium-tinoxid surfaces were measured.

PMID- 9768470
TI  - Tertiary structure of the hepatic cell protein fibrinogen in fluid revealed by
      atomic force microscopy.
AB  - Fibrinogen participates in important cellular physiological processes, such as
      cell adhesion and blood clotting. Although the primary and secondary structures
      of fibrinogen are known, its tertiary structure is yet to be determined. In
      attempts to understand the tertiary structure of this important hydrated cellular
      and plasma membrane protein, the present study using atomic force microscopy was
      carried out. The techniques presented in this manuscript may also be applicable
      to enhance the imaging of live cells as well as their subcellular components. The
      authors have imaged fibrinogen by Tapping Mode atomic force microscopy in fluid.
      Purified human fibrinogen, together with 15-nm colloidal gold particles serving
      as an internal calibration standard, were adhered to a poly-L-lysine substrate on
      freshly cleaved mica. Atomic force microscopy images were obtained using oxide
      sharpened silicon nitride probes, either unaltered or with an electron beam
      deposited extended tip. Although various structures were observed, the
      predominant forms consisted of a bi- or trinodular slightly curved linear shape.
      Approximately 300 of these structures were observed with six different tips (1
      unaltered and 5 electron beam deposited) and their lengths and heights were
      analyzed. The mean length of the fibrinogen molecules was 65.8 nm and the mean
      height was 3.4 nm. The quantitative measurements were little influenced by the
      shape of the tip, whereas the sharper electron beam deposited tips seemed to
      produce qualitatively superior images.

PMID- 9768471
TI  - An atomic force microscopic examination of the apical membrane of the mammalian
      gastric gland.
AB  - The authors have examined the morphology of the apical membrane of living gastric
      glands from both the rat and rabbit with an atomic force microscope using both a
      conventional upright configuration and in the new inverted bioscope mode.
      Individual gastric glands were hand dissected and the apical membrane was exposed
      using a microsurgical approach. The split open glands allowed to access and
      directly image 4-6 cells with their apical axis available to the scanning tip of
      the atomic force microscope. All cells were scanned in a physiological Ringer
      solution at 37 degrees C. The scans revealed that we could visualize both
      parietal and chief cells and to distinguish them via their unique apical
      topography. The parietal cells showed a variety of small canaliculi that were
      dispersed along the apical axis of the cell. Scans of chief cells revealed an
      apical surface that was covered with microvilli along the entire apical margin.
      The results of these studies show that it is indeed feasible to image living
      gastric glands at 37 degrees C and to observe the surface topology of both the
      parietal and chief cell.

PMID- 9768472
TI  - The atomic force microscope detects ATP-sensitive protein clusters in the plasma
      membrane of transformed MDCK cells.
AB  - Plasma membrane proteins are supposed to form clusters that allow 'functional
      cross-talk' between individual molecules within nanometre distance. However, such
      hypothetical protein clusters have not yet been shown directly in native plasma
      membranes. Therefore, we developed a technique to get access to the inner face of
      the plasma membrane of cultured transformed kidney (MDCK) cells. The authors
      applied atomic force microscopy (AFM) to visualize clusters of native proteins
      protruding from the cytoplasmic membrane surface. We used the K+ channel blocker
      iberiotoxin (IBTX), a positively charged toxin molecule, that binds with high
      affinity to plasma membrane potassium channels and to atomically flat mica. Thus,
      apical plasma membranes could be 'glued' with IBTX to the mica surface with the
      cytosolic side of the membrane accessible to the scanning AFM tip. The topography
      of these native inside-out membrane patches was imaged with AFM in electrolyte
      solution mimicking the cytosol. The plasma membrane could be clearly identified
      as a lipid bilayer with the characteristic height of 4.9 +/- 0.02 nm. Multiple
      proteins protruded from the lipid bilayer into the cytosolic space with molecule
      heights between 1 and 20 nm. Large protrusions were most likely protein clusters.
      Addition of the proteolytic enzyme pronase to the bath solution led to the
      disappearance of the proteins within minutes. The metabolic substrate ATP induced
      a shape-change of the protein clusters and smaller subunits became visible. ADP
      or the non-hydrolysable ATP analogue, ATP-gamma-S, could not exert similar
      effects. It is concluded that plasma membrane proteins (and/or membrane
      associated proteins) form 'functional clusters' in their native environment. The
      'physiological' arrangement of the protein molecules within a cluster requires
      ATP.

PMID- 9768473
TI  - Using atomic force microscopy to investigate patch-clamped nuclear membrane.
AB  - Nuclear patch clamp is an emerging research field that aims to disclose the
      electrical phenomena underlying macromolecular transport across the nuclear
      envelope (NE), its properties as an ion barrier and its function as an
      intracellular calcium store. The authors combined the patch clamp technique with
      atomic force microscopy (AFM) to investigate the structure-function relationship
      of NE. In principle, patch clamp currents, recorded from the NE can indicate the
      activity of the nuclear pore complexes (NPCs) and/or of ion channels in the two
      biomembranes that compose the NE. However, the role of the NPCs is still nuclear
      because the observed NE current in patch clamp experiments is lower than expected
      from the known density of the NPCs. Therefore, AFM was applied to link patch
      clamp currents to structure. The membrane patch was excised from the nuclear
      envelope and, after electrical evaluation, transferred from the patch pipette to
      a substrate. We could identify the native nuclear membrane patches with AFM at a
      lateral and a vertical resolution of 3 nm and 0.1 nm, respectively. It was shown
      that complete NE together with NPCs can be excised from the nucleus after their
      functional identification in patch clamp experiments. However, we also show that
      membranes of the endoplasmic reticulum can contaminate the tip of the patch
      pipette during nuclear patch clamp experiments. This possibility must be
      considered carefully in nuclear patch clamp experiments.

PMID- 9768474
TI  - Rapid aldosterone-induced cell volume increase of endothelial cells measured by
      the atomic force microscope.
AB  - Atomic force microscopy (AFM) is a useful technique for imaging the surface of
      living cells in three dimensions. The authors applied AFM to obtain morphological
      information of individual cultured endothelial cells of bovine aorta under
      stationary and strain conditions and to simultaneously measure changes in cell
      volume in response to aldosterone. This mineralocorticoid hormone is known to
      have acute, non-genomic effects on intracellular pH, intracellular electrolytes
      and inositol-1,4,5-triphosphate production. In this study whether endothelial
      cells under tension change their volume in response to aldosterone was tested.
      Such changes were already shown in human leukocytes measured by Coulter counter.
      In contrast to leukocytes that are more or less spherical and live in suspension,
      endothelial cells exhibit a complex morphology and adhere to a substrate. Thus,
      measurements of discrete cell volume changes in endothelial cells under
      physiological condition is only feasible with more sophisticated techniques. By
      using AFM we could precisely measure the absolute cell volume of individual
      living endothelial cells. Before the addition of aldosterone the cell volume of
      mechanically stressed endothelial cells mimicking arterial blood pressure was
      1827 +/- 172 fl. Cell volume was found to increase by 28% 5 min after hormone
      exposure. Twenty-five minutes later cell volume was back to normal despite the
      continuous presence of aldosterone in the medium. Amiloride, a blocker of the
      plasma membrane Na+/H+ exchanger prevented the initial aldosterone-induced volume
      increase. Taken together, AFM disclosed a transient swelling of endothelial cells
      induced by the activation of an aldosterone sensitive plasma membrane Na+/H+
      exchanger.

PMID- 9768475
TI  - A non-invasive method for the tight anchoring of cells for scanning force
      microscopy.
AB  - Use of scanning force microscopy (SFM) for high resolution imaging of cell
      surfaces requires the cells to be tightly attached to substrates. Imaging of
      loosely adhered RBL-2H3 cells enabled determination of the cell size and
      investigation of larger structures and pseudopodia but failed in resolving more
      detail. Immobilization under non-invasive conditions via flexible crosslinkers
      containing a hydrophobic anchoring group enhanced resolution enormously. The
      cells were tightly attached to the substrates and were not removed by shear
      forces up to 80 nN as determined in a flow through apparatus. Morphological
      structures and dynamic processes on cell surfaces were observed as well as
      structural changes after cell stimulation upon ionomycin treatment. Molecular or
      atomic resolution, however, was not attainable which is attributed to the
      displacement of the flexible cell surface due to shear forces arising from the
      scanning tip during contact mode.

PMID- 9768476
TI  - Sleep schedules and daytime functioning in adolescents.
AB  - Sleep and waking behaviors change significantly during the adolescent years. The
      objective of this study was to describe the relation between adolescents'
      sleep/wake habits, characteristics of students (age, sex, school), and daytime
      functioning (mood, school performance, and behavior). A Sleep Habits Survey was
      administered in homeroom classes to 3,120 high school students at 4 public high
      schools from 3 Rhode Island school districts. Self-reported total sleep times
      (school and weekend nights) decreased by 40-50 min across ages 13-19, ps < .001.
      The sleep loss was due to increasingly later bedtimes, whereas rise times were
      more consistent across ages. Students who described themselves as struggling or
      failing school (C's, D's/F's) reported that on school nights they obtain about 25
      min less sleep and go to bed an average of 40 min later than A and B students, ps
      < .001. In addition, students with worse grades reported greater weekend delays
      of sleep schedule than did those with better grades. Furthermore, this study
      examined a priori defined adequate sleep habit groups versus less than adequate
      sleep habit groups on their daytime functioning. Students in the short school
      night total sleep group (< 6 hr 45 min) and/or large weekend bedtime delay group
      (> 120 min) reported increased daytime sleepiness, depressive mood, and
      sleep/wake behavior problems, ps < .05, versus those sleeping longer than 8 hr 15
      min with less than 60 min weekend delay. Altogether, most of the adolescents
      surveyed do not get enough sleep, and their sleep loss interferes with daytime
      functioning.

PMID- 9768477
TI  - Using writing instruments: invariances in young children and adults.
AB  - In 2 studies, developmental changes in variability associated with handwriting
      were investigated. In Study 1, variability in grip patterns and pen positioning
      relative to a flat surface were examined in 3- and 5-year-olds and adults. The
      results indicated that between 3 and 5 years of age there is a reduction in the
      number of grips that individual children routinely use and a reduction in
      variability associated with pen-surface positioning. In Study 2, the 3-year-old
      children who participated in Study 1 were tested 6 months later. In comparison to
      young 3-year-old children, older 3-year-olds use an adult grip pattern more often
      and are less variable in pen-surface positioning, although the use of multiple
      grip patterns is still common. The findings from both studies are considered in
      relation to prior research that emphasized modal patterns of motor development
      and newer work that uses developmental changes in variability to understand the
      acquisition of motor skill.

PMID- 9768478
TI  - Preliminary models of risk and protective factors for childhood homesickness:
      review and empirical synthesis.
AB  - Empirical research and conventional wisdom have suggested numerous risk and
      protective factors for the development of homesickness. Yet no study has
      integrated predictors and sequelae of homesickness into a testable statistical
      model. As a first step in developing a pathogenic model of homesickness in
      children, this study measured, factor analyzed, and modeled 14 predictors and 8
      sequelae of homesickness. Using a sample of 293 boys, ages 8-16, spending 2 weeks
      at an overnight summer camp, this study tested 2 alternate models, focusing on
      the roles of boys' interpersonal attitudes, perceived control, and separation
      expectations in the subsequent development of homesickness. Results indicated
      that interpersonal attitudes and perceived control may predict boys'
      preseparation beliefs about whether they will become homesick. This "homesick
      disposition" combines with little prior separation experience to account for 69%
      of the variance in self-reported homesickness. Homesickness was not a powerful
      predictor of negative emotion, whereas interpersonal attitudes and perceived
      control predicted 70% of the variance in negative emotion. Results are discussed
      in the context of contemporary theories of homesickness.

PMID- 9768479
TI  - Is there a "trochaic bias" in early word learning? Evidence from infant
      production in English and French.
AB  - Studies of speech perception and segmentation in the prelinguistic period, early
      word production, and patterns of function word omission in early syntax have all
      recently emphasized the role of the trochaic accentual pattern in English,
      sometimes positing a universal trochaic bias. We make use of perceptual and
      acoustic analyses of words and babble from 9 children acquiring English and 5
      acquiring French in the late single-word period (13-20 months) to provide a
      direct test for the existence of such a bias. Neither English nor French infant
      vocalizations were exclusively trochaic. The iambic productions of American
      infants were traced to the presence of iambic phrases in the input. Differences
      between English and French in the acoustic realization of accent in infant
      vocalizations were also traceable to adult patterns. However, the almost bipolar
      distribution of trochaic and iambic patterns in the data from English-learning
      infants was ultimately traceable to the integration of prosodic and segmental
      patterning in individual child word production templates, themselves arguably the
      product of an earlier acting articulatory filter.

PMID- 9768480
TI  - The medium can obscure the message: young children's understanding of video.
AB  - In the first few years of life, children acquire a great deal of general
      information through symbolic media, including television. Here we explored
      whether very young children would use information presented via video to solve a
      retrieval problem. The children watched on a monitor as a toy was hidden in the
      room next door. A group of 2 1/2-year-olds was very successful at finding the
      hidden toy based on the televised hiding event, but a group of 2-year-olds was
      not. Substantially better performance was achieved by other 2-year-olds who
      either watched the hiding event directly through a window or who believed they
      were watching directly (but were in fact looking at the monitor through the
      window). These results (like those from other symbolic media such as models and
      pictures) indicate that very young children have difficulty using a symbolic
      representation as a source of information about an existing situation.

PMID- 9768481
TI  - Intention and knowledge in preschoolers' conception of pretend.
AB  - Experiments 1 and 2 investigated 3- and 4-year-olds' understanding of the
      intended nature of pretend behaviors by testing their ability to distinguish
      between involuntary behaviors and the same behaviors emitted intentionally
      through acts of pretend. Four-year-olds' high rate of passing showed that (1)
      they understood intention as a mental cause of action and (2) they construed
      pretend behaviors mentalistically. Experiment 3 used the same contrastive
      procedure to examine Lillard's contention that 4-year-olds do not understand the
      knowledge conditions and hence the mental representational component of pretend
      actions. Whereas nearly all of the 5-year-olds understood that an agent who did
      not know of a specific animal could not be pretending to be that animal, 4-year
      olds systematically associated ignorance with pretend. On the basis of the
      combined findings of the present experiments, and other research showing a
      mentalistic understanding of pretense by the age of 3 or 4, it was concluded that
      the specific reasoning requirements of Lillard's tasks resulted in an
      underestimation of children's appreciation of the mental features of pretend.

PMID- 9768482
TI  - Wanting to be it: children's understanding of intentions underlying pretense.
AB  - How children understand the mental state of pretense has recently become an
      active area of inquiry, with some research suggesting that young children do not
      understand that pretending is based on mentally representing some alternate state
      of affairs. Because intention is thought to be understood earlier than mental
      representation generally, these experiments tested whether children understand
      pretense intentions at an earlier age than they understand pretense mental
      representations. Children were told about a character's intentions and
      conflicting actions, and were asked about the character's pretense. Across 5
      experiments, children did not demonstrate appreciation that intention is crucial
      to pretense. Various methodological factors that might have compromised the
      results were examined, but to no effect.

PMID- 9768483
TI  - Individual differences in contextual facilitation: evidence from dyslexia and
      poor reading comprehension.
AB  - Ninety-two 7- to 10-year-old children read words presented in isolation or
      following a spoken sentence context. In absolute terms, poor readers showed more
      contextual facilitation than good readers. However, when the relative benefit of
      context was assessed, this was greater for children with better reading skills,
      and comprehension was a better predictor of contextual facilitation than
      decoding. Study 2 compared the performance of dyslexics with that of reading-age
      matched poor comprehenders and normal readers. The dyslexics showed greater
      contextual facilitation than the normal readers who, in turn, showed more priming
      than poor comprehenders. The results show that dyslexic children use context to
      compensate for poor decoding skills, whereas children with poor reading
      comprehension skills fail to benefit from context as much as normal readers.

PMID- 9768484
TI  - Environmental input and cognitive growth: a study using time-period comparisons.
AB  - In this study, we examined the relation of input to cognitive growth in a single
      population of children. We studied 4 domains: Language, Spatial Operations,
      Concepts, and Associative Memory. Four groups of children drawn from the same
      population were tested in October of kindergarten, April of kindergarten, October
      of first grade, and April of first grade. These time points are 6 months apart,
      but they span periods that differ in amount of school input children receive.
      Much greater growth was found over time periods with greater amounts of school
      input (October to April) than over time periods with less school input (April to
      October) for Language, Spatial Operations, and Concepts, but not for Associative
      Memory. These findings suggest that amount of input is causally related to
      cognitive growth in particular domains.

PMID- 9768485
TI  - Structure, stability, and development of young children's self-concepts: a
      multicohort-multioccasion study.
AB  - A new, individual administration procedure for assessing multiple dimensions of
      self-concept for young children 5-8 years of age (Marsh, Craven, & Debus) was the
      basis of this study. We expanded this application in a multicohort-multioccasion
      (MCMO) study that provides simultaneous multicohort comparisons (cross-sectional
      comparisons of different age cohorts) and longitudinal comparisons of the same
      children on multiple occasions. There was reasonable support for predictions that
      reliability, stability, factor structure, and the distinctiveness of the SDQ
      factors would improve with age (a between-group age cohort comparison) and from 1
      year to the next (a longitudinal comparison), and that small gender differences
      were reasonably stable over age. Consistent with the proposal that children's
      self-perceptions become more realistic with age, Time 1 (T1) teacher ratings were
      more highly correlated with student self-ratings at T2 than T1 and contributed to
      the prediction of T2 self-concept beyond effects mediated by T1 self-concepts.
      The results support and expand the surprisingly good support for the
      multidimensionality of self-concept responses for very young children using this
      procedure.

PMID- 9768486
TI  - Age trends in the use of social and temporal comparison for self-evaluation:
      examination of a novel developmental hypothesis.
AB  - Two studies tested the novel hypothesis that children use social comparison (SC)
      for self-appraisal at an earlier age than they do temporal comparison (TC). The
      effect of other's and of own prior outcome on performance and ability appraisal
      and on self-evaluative strategies was examined using simple tasks and outcome
      information. Results from 840 children at ages 4-8 confirmed that self-evaluative
      SC was similar over age. Even 4- to 5-year-olds rated themselves higher after
      doing better versus worse than another and explained their ratings in terms of
      explicit SC. Social failure undermined continuing motivation at all ages. In
      contrast, young children in TC conditions attended only to their last outcome,
      and comparisons between current and prior outcomes increased with age. Self
      evaluative biases were marked at age 5-6 and for boys in SC conditions. Results
      clarify the role of cognitive and motivational factors in the development of SC
      and TC.

PMID- 9768487
TI  - Rejection sensitivity and children's interpersonal difficulties.
AB  - Some children respond to social rejection in ways that undermine their
      relationships, whereas others respond with more equanimity. This article reports
      3 studies that test the proposition that rejection sensitivity--the disposition
      to defensively (i.e., anxiously or angrily) expect, readily perceive, and
      overreact to social rejection--helps explain individual differences in response
      to social rejection. Data were from urban, minority (primarily Hispanic and
      African American) fifth to seventh graders. Study 1 describes the development of
      a measure of rejection sensitivity for children. Study 2 provides experimental
      evidence that children who angrily expected rejection showed heightened distress
      following an ambiguously intentioned rejection by a peer. Study 3 shows that
      rejection sensitive children behaved more aggressively and experienced increased
      interpersonal difficulties and declines in academic functioning over time.

PMID- 9768488
TI  - A three year follow-up of attachment and indiscriminate friendliness in children
      adopted from Romanian orphanages.
AB  - Attachment and indiscriminately friendly behavior were assessed in children who
      had spent at least 8 months in a Romanian orphanage (RO) and two comparison
      groups of children: a Canadian-born, nonadopted, never institutionalized
      comparison group (CB) and an early adopted comparison group adopted from Romania
      before the age of 4 months (EA). Attachment was assessed using 2 measures: an
      attachment security questionnaire based on parent report, and a Separation
      Reunion procedure that was coded using the Preschool Assessment of Attachment.
      Indiscriminately friendly behavior was examined using parents' responses to 5
      questions about their children's behavior with new adults. Although RO children
      did not score differently from either CB or EA children on the attachment
      security measure based on parent report, they did display significantly more
      insecure attachment patterns than did children in the other 2 groups. In
      addition, RO children displayed significantly more indiscriminately friendly
      behavior than both CB and EA children, who did not differ in terms of
      indiscriminate friendliness. RO children's insecure attachment patterns were not
      associated with any aspect of their institutional environment, but were related
      to particular child and family characteristics. Specifically, insecure RO
      children had more behavior problems, scored lower on the Stanford-Binet
      Intelligence Scale, and had parents who reported significantly more parenting
      stress than RO children classified as secure.

PMID- 9768489
TI  - A prospective longitudinal study of attachment disorganization/disorientation.
AB  - The research explores the antecedents and consequences of attachment
      disorganization from a prospective longitudinal perspective. The relations of
      attachment disorganization/disorientation to endogenous (e.g., maternal medical
      history, infant temperament) and environmental (e.g., maternal caregiving
      quality, infant history of abuse) antecedents and to behavioral consequences from
      24 months to 19 years are examined. For the 157 participants in the longitudinal
      study, attachment disorganization was correlated significantly with environmental
      antecedents (e.g., maternal relationship and risk status, caregiving quality, and
      infant history of maltreatment), but not with available endogenous antecedents.
      Infant history of attachment disorganization was correlated with consequent
      variables related to mother-child relationship quality at 24 and 42 months, child
      behavior problems in preschool, elementary school and high school, and
      psychopathology and dissociation in adolescence. Structural models suggest that
      disorganization may mediate the relations between early experience and later
      psychopathology and dissociation. The findings are considered within a
      developmental view of psychopathology, that is, pathology defined in terms of
      process, as a pattern of adaptation constructed by individuals in their
      environments.

PMID- 9768490
TI  - Growing or just getting along? Technical and adaptive competence in coping among
      adolescents.
AB  - This study examined coping among African American adolescents with learning
      disabilities. Ninety-seven African American adolescents and their mother or
      primary caregiver participated in the study. The study centered on a new
      conceptual distinction between technical competence in coping and adaptive
      competence in coping. Technical competence referred to short-term, reactive
      attempts at coping based on individuals' abilities to find techniques for
      reducing their feelings of distress. Adaptive competence referred to longer-term,
      developmental processes of adaptive change that resulted in more global benefits
      for the individual. Past literature was reassessed on the basis of this
      conceptual distinction, and a new model of technical and adaptive competence in
      coping was proposed based on developmental theory. Perceptions of coping efficacy
      and the incidence of behavioral problems were regressed on measures of technical
      and adaptive competence in coping. Results were explored first as a general test
      of the model on the total sample, and second as a comparative analysis between
      gender subsamples. Total sample findings were consistent with hypothesized
      results. Technical competence was a better predictor of feelings of efficacy and
      adaptive competence was a better predictor of behavioral problems. Gender
      subsample differences were significant and supported a picture of gender-typed
      approaches to coping.

PMID- 9768491
TI  - Early child care and self-control, compliance, and problem behavior at twenty
      four and thirty-six months. The NICHD Early Child Care Research Network.
AB  - To evaluate child-care effects on young children's self-control, compliance, and
      problem behavior, children enrolled in the NICHD Study of Early Child Care were
      tested and observed in the laboratory and in child care at 24 and 36 months, and
      mothers and caregivers completed questionnaires. Indicators of child-care
      quantity, quality, stability, type, and age of entry, along with measures of
      family background, mothering, and child characteristics obtained through the
      first 3 years of life were used to predict 2 and 3 year child functioning.
      Results revealed (1) mothering to be a stronger and more consistent predictor of
      child outcomes than child care; (2) little evidence that early, extensive, and
      continuous care was related to problematic child behavior, in contrast to results
      from earlier work; (3) that among the child-care predictors, child-care quality
      was the most consistent predictor of child functioning, although limited variance
      could be explained by any (or all) child-care variables; and (4) that virtually
      none of the anticipated interactions among child-care factors or between them and
      family or child measures proved significant.

PMID- 9768492
TI  - Peer relationships and self-esteem among children who have been maltreated.
AB  - A prospective longitudinal design was employed to assess risks associated with
      maltreatment in a representative community sample of 107 maltreated children and
      an equal number of nonmaltreated comparison children. Heightened difficulties in
      peer relationships and self-esteem were associated with greater severity and
      chronicity of maltreatment. For example, children who experienced chronic
      maltreatment were less well-liked by peers. Type of maltreatment was also related
      to specific aspects of children's adjustment. For instance, sexual abuse
      predicted low self-esteem, but not problems in peer relationships. Emotional
      maltreatment, on the other hand, was related to difficulties in peer
      relationships, but not to low self-esteem. Thus, the best predictions of specific
      aspects of children's adjustment were provided by considering timing, type, and
      severity of maltreatment. For some groups of maltreated children, having a good
      friend was associated with improvement over time in self-esteem.

PMID- 9768494
TI  - The development of display rule knowledge: linkages with family expressiveness
      and social competence.
AB  - The development of display rule knowledge and its associations with family
      expressiveness (Study 1) and peer competence (Study 2) were investigated among
      elementary school children. In Study 1, the display rule knowledge of 121
      kindergartners and third graders was assessed using validated hypothetical
      scenarios. There were significant grade differences in display rule knowledge
      such that third graders compared to kindergartners more frequently combined
      expression regulation with prosocial reasoning, norm-maintenance, and self
      protective motives. Maternal reports of family emotional climates indicated that
      aspects of negative expressiveness were related positively to self-protective
      display rules and negatively to prosocial display rules. Study 2 included 93
      third and fifth graders who reported on their display rule knowledge and on their
      emotional reactions and strategies to resolve peer conflict. Classmates and
      teachers provided ratings on social competence. Age differences for display rule
      knowledge were not documented, but prosocial display rules were most consistently
      related to hypothetical peer conflict responses and social competence. The
      findings confirm that display rule knowledge is related in consistent and
      systematic ways to what children learn within the family emotional context, how
      they propose to resolve peer conflict, and how they are perceived by peers and
      teachers.

PMID- 9768495
TI  - Child development, molecular genetics, and what to do with genes once they are
      found.
AB  - Genes associated with behavioral dimensions and disorders are beginning to be
      identified. Although it is difficult and expensive to find genes associated with
      behavior, it is relatively easy and inexpensive to use genes that have already
      been identified. We describe how genes are found, but the main goal of this
      article is to outline what developmentalists can do with genes once they are
      found and, hence, to encourage the use of DNA markers in developmental research.
      We suggest that genes can be used to answer questions about developmental
      continuities, about psychopathological patterns, and about environmental risk
      mechanisms. Developmental questions include the causal mechanisms involved in
      heterotypic continuity. Questions on psychopathological patterns address
      heterogeneity (Do gene-behavior associations apply to disorders or to separate
      components representing risk or protective factors?), comorbidity (Are gene
      behavior associations diagnosis-specific?), and the links between normality and
      disorder (Does a gene-behavior association for a disorder extend to related
      dimensions of normal variation and vice versa?). Questions about environmental
      risk mechanisms are informed by study of gene-environment interaction (Are
      individuals who are at genetic risk more sensitive to specific psychosocial
      risks?) and gene-environment correlation (Are individuals who are at genetic risk
      more likely to be exposed to psychosocial risk?).

PMID- 9768496
TI  - Low mitochondrial diversity and small effective population sizes of the copepods
      Calanus finmarchicus and Nannocalanus minor: possible impact of climatic
      variation during recent glaciation.
AB  - Molecular population genetic diversity of two planktonic copepods of the North
      Atlantic, Calanus finmarchicus and Nannocalanus minor (Crustacea, Copepoda,
      Calanoida), was characterized using the sequence variation in a 350 bp region of
      the mitochondrial 16S rRNA gene. The subarctic species, C. finmarchicus, shows
      lower population genetic diversity (haplotype diversity, h = 0.368, SD = 0.043;
      nucleotide diversity, pi = 0.00370, SD = 0.0026) than the temperate/subtropical
      species, N. minor (h = 0.824, SD = 0.024; pi = 0.00502, SD = 0.0032). Effective
      population sizes (N(e), estimated from numbers of haplotypes) and effective
      female population sizes (Nf(e), estimated from nucleotide diversities) for the
      two species are 10(7) to 10(10) smaller than census female population sizes (Nf)
      estimated from observed densities and areal distributions. For both C.
      finmarchicus and N. minor, Nf approximately 10(15), N(e) approximately 10(8), and
      Nf(e) approximately 10(5). We hypothesize that the cause of both low levels of
      molecular diversity and small effective population sizes of the two species is
      the impact of glaciation during the past 20,000 years. C. finmarchicus may have
      experienced 75% range reduction and latitudinal displacement during the last
      glacial maximum at 18,000 years BP, giving rise to a genetic bottleneck; this may
      explain low diversity and an L-shaped distribution of pairwise haplotype
      differences. In contrast, N. minor may have experienced range reduction of only
      30% and less change in latitudinal extent, with less impact of levels of
      molecular diversity and the shape of the pairwise difference distribution.
      Although marine zooplankton species are highly abundant, conservation biologists
      should note that their numbers may vary significantly on climatic to evolutionary
      time scales, generating low levels of molecular genetic diversity.

PMID- 9768497
TI  - Species identification using genetic tools: the value of nuclear and
      mitochondrial gene sequences in whale conservation.
AB  - DNA sequence analysis is a powerful tool for identifying the source of samples
      thought to be derived from threatened or endangered species. Analysis of
      mitochondrial DNA (mtDNA) from retail whale meat markets has shown consistently
      that the expected baleen whale in these markets, the minke whale, makes up only
      about half the products analyzed. The other products are either unregulated small
      toothed whales like dolphins or are protected baleen whales such as humpback,
      Bryde's, fin, or blue whales. Independent verification of such mtDNA
      identifications requires analysis of nuclear genetic loci, but this is
      technically more difficult than standard mtDNA sequencing. In addition, evolution
      of species-specific sequences (i.e., fixation of sequence differences to produce
      reciprocally monophyletic gene trees) is slower in nuclear than in mitochondrial
      genes primarily because genetic drift is slower at nuclear loci. When will use of
      nuclear sequences allow forensic DNA identification? Comparison of neutral
      theories of coalescence of mitochondrial and nuclear loci suggests a simple rule
      of thumb. The "three-times rule" suggests that phylogenetic sorting at nuclear
      loci is likely to produce species-specific sequences when mitochondrial alleles
      are reciprocally monophyletic and the branches leading to the mtDNA sequences of
      a species are three times longer than the average difference observed within
      species. A preliminary test of the three-times rule, which depends on many
      assumptions about the species and genes involved, suggests that blue and fin
      whales should have species-specific sequences at most neutral nuclear loci,
      whereas humpback and fin whales should show species-specific sequences at fewer
      nuclear loci. Partial sequences of actin introns from these species confirm the
      predictions of the three-times rule and show that blue and fin whales are
      reciprocally monophyletic at this locus. These intron sequences are thus good
      tools for the identification of these species and will afford a chance to
      identify putative hybrid blue/fin whales thought to have entered the retail
      market after 1989.

PMID- 9768498
TI  - Analysis of di-n-butylphthalate biotransformation in cattle by liquid
      chromatography/ion trap mass spectrometry/mass spectrometry.
AB  - The nature of products of contamination intake were investigated in cattle dosed
      with [14C]di-n-butylphthalate (DBP). Radio-labelled metabolites were extracted
      from bile, faeces, plasma and urine onto solid-phase media, fractionated by ion
      exchange chromatography, separated by reverse phase HPLC and analysed by negative
      ion atmospheric pressure chemical ionization mass spectrometry(n) (LCQ,
      Finnigan). All matrices contained a common major metabolite [deprotonated
      molecular ion (M-H)- m/z 221] which coeluted with and had an identical daughter
      ion spectrum to reference monobutylphthalate (MBP). MBP was metabolised to a beta
      glucuronidase sensitive compound (M-H)- m/z 397 whose spectrum contained daughter
      ions (m/z 175 and 221) consistent with the parent glucuronide. A further three
      beta-glucuronidase resistant radio-labelled metabolites were also produced (M-H-
      m/z 165, 193 and 237); comparison of daughter ion spectra with those of reference
      MBP and phthalic acid indicated identity with phthalic acid, monoethylphthalate
      (MEP) and monohydroxybutylphthalate (MHBP) respectively. The presence of a
      benzoate daughter ion (m/z 121) in all spectra was indicative of side chain
      biotransformation. Both MBP and MEP contained a phthalate daughter ion (m/z 165)
      indicating loss of a butyl and ethyl side chain respectively. A daughter ion of
      m/z 89 derived from the side chain provided evidence that the third metabolite
      was MHBP. Incubation of DBP with isolated bovine hepatocytes produced the same
      metabolites and provided relatively clean samples for LC/MSn analysis. Detection
      of these DBP metabolites in meat or dairy food products will provide evidence for
      environmental exposure and biotransformation in vivo, whereas the presence of the
      parent compound would suggest contamination during food processing and packaging.

PMID- 9768499
TI  - Characterization of enzymatic pectin digests by matrix-assisted laser
      desorption/ionization mass spectrometry.
AB  - The use of matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry for the characterization of partially methyl-esterified enzymatic
      pectin digests is described. The sensitivities of several matrices, positive and
      negative ion modes and desalting techniques for these acidic oligosaccharides
      were compared. The most favorable results were obtained with a thin-layer
      preparation of a mixture of 2,4,6-trihydroxyacetophenone and nitrocellulose in
      the negative ion mode. Results are presented demonstrating the sensitive
      characterization of separated and unseparated high-ester pectin digests obtained
      after complete digestion using Aspergillus niger pectin lyase and the analysis of
      digests after chemical modification. In the case of unseparated digests, the
      analysis of methylation patterns is demonstrated. Oligomers with a degree of
      polymerization up to 40 were detected after enrichment of large oligomers by
      propan-2-ol precipitation.

PMID- 9768500
TI  - Precolumn derivatization and capillary liquid chromatographic/frit-fast atom
      bombardment mass spectrometric analysis of cytokinins in Arabidopsis thaliana.
AB  - New cytokinin derivatives with high surface activity were developed for capillary
      liquid chromatography/frit-fast atom bombardment (FAB) mass spectrometry.
      Propionyl ester derivatives of cytokinin nucleosides and glucosides and
      benzylamine derivatives of cytokinin bases gave stronger [M + H]+ ion currents
      than the underivatized compounds. In trace analysis by selective reaction
      monitoring, low (fmole) detection limits were found. In qualitative analysis by
      B/E-linked scanning, the derivatives also gave more spectral information, owing
      to the presence of fragment ions, diagnostic for the sugar moieties of
      nucleosides and glucosides, not present in the spectra of underivatized
      compounds. THe proposed FAB method was used to identify and quantify 10
      isoprenoid cytokinins in Arabidopsis thaliana, including free bases, nucleosides,
      nucleotides and glucosides.

PMID- 9768501
TI  - Pelvic limb musculature in the emu Dromaius novaehollandiae (Aves:
      Struthioniformes: Dromaiidae): adaptations to high-speed running.
AB  - Emus provide an excellent opportunity for studying sustained high-speed running
      by a bird. Their pelvic limb musculature is described in detail and morphological
      features characteristic of a cursorial lifestyle are identified. Several
      anatomical features of the pelvic limb reflect the emus' ability for sustained
      running at high speeds: (1) emus have a reduced number of toes and associated
      muscles, (2) emus are unique among birds in having a M. gastrocnemius, the most
      powerful muscle in the shank, that has four muscle bellies, not the usual three,
      and (3) contribution to total body mass of the pelvic limb muscles of emus is
      similar to that of the flight muscles of flying birds, whereas the pelvic limb
      muscles of flying birds constitute a much smaller proportion of total body mass.
      Generally, the pelvic limb musculature of emus resembles that of other ratites
      with the notable exception of M. gastrocnemius. The presence and arrangement of
      four muscle bellies may increase the effectiveness of M. gastrocnemius and other
      muscles during cursorial locomotion by moving the limb in a cranio-caudal rather
      than a latero-medial plane.

PMID- 9768502
TI  - Contribution of the vertebral artery to cerebral circulation in the rat snake
      Elaphe obsoleta.
AB  - Blood supplying the brain in vertebrates is carried primarily by the carotid
      vasculature. In most mammals, cerebral blood flow is supplemented by the
      vertebral arteries, which anastomose with the carotids at the base of the brain.
      In other tetrapods, cerebral blood is generally believed to be supplied
      exclusively by the carotid vasculature, and the vertebral arteries are usually
      described as disappearing into the dorsal musculature between the heart and head.
      There have been several reports of a vertebral artery connection with the
      cephalic vasculature in snakes. We measured regional blood flows using
      fluorescently labeled microspheres and demonstrated that the vertebral artery
      contributes a small but significant fraction of cerebral blood flow
      (approximately 13% of total) in the rat snake Elaphe obsoleta. Vascular casts of
      the anterior vessels revealed that the vertebral artery connection is indirect,
      through multiple anastomoses with the inferior spinal artery, which connects with
      the carotid vasculature near the base of the skull. Using digital subtraction
      angiography, fluoroscopy, and direct observations of flow in isolated vessels, we
      confirmed that blood in the inferior spinal artery flows craniad from a point
      anterior to the vertebral artery connections. Such collateral blood supply could
      potentially contribute to the maintenance of cerebral circulation during
      circumstances when craniad blood flow is compromised, e.g., during the
      gravitational stress of climbing.

PMID- 9768503
TI  - Compressive loading on bone surfaces from muscular contraction: an in vivo study
      in the miniature pig, Sus scrofa.
AB  - Several authors have speculated that muscles contracting adjacent to bony
      surfaces may cause compressive loads against the bone and thus influence skull
      development. This study was undertaken to evaluate the premise of this argument.
      A flat, semiconductor pressure transducer was surgically placed on bony surfaces
      beneath muscle attachments. Pressures were recorded during normal mastication (n
      = 7) and while overlying muscles were stimulated in anesthetized pigs (n = 15).
      The transducer was highly specific; no pressure was recorded in quiescent or
      passively stretched muscles or when other muscles were stimulated. Contraction of
      the overlying muscles exerted high normal loads on the bone, always exceeding
      systolic blood pressure (16 kPa). Temporal fossa pressure during mastication
      followed temporalis electromyographic (EMG) signals with a lag period
      approximating the twitch contraction time. When three different sites were
      compared in anesthetized animals, compressive load was highest on the temporal
      fossa (111.4 +/- 56.5 kPa, n = 15), intermediate on the mandibular angle (58.4 +/
      28.3 kPa, n = 4), and lowest on the medial side of the zygomatic arch (37.2 +/-
      19.7 kPa, n = 15). Pressure amplitudes were not related to body size or relative
      muscle size. Muscle complexity and compartmental constraints did appear to
      influence pressure. Disruption of the external aponeurosis of the masseter
      decreased pressure on the mandibular angle by 45%, confirming the importance of
      tendinous constraint in determining pressure production. Thus, contracting
      muscles exert substantial but site-specific compressive loads on adjacent bone
      surfaces.

PMID- 9768504
TI  - Effects of step size and break-point criterion on progressive-ratio performance.
AB  - Key pecking by pigeons was maintained by arithmetic progressive-ratio schedules
      of food delivery. Successive conditions arranged different step sizes, and each
      condition remained in effect until behavior appeared stable. Each session
      continued until a period of time passed in which no key pecks were recorded (the
      break-point criterion); both a 5-min and a 15-min criterion were tested across a
      range of step sizes. Average breaking points (i.e, the largest ratio completed)
      were relatively unaffected by step-size magnitude, whereas the average number of
      ratios completed and average response rates generally declined across increasing
      step sizes. Within sessions, preratio pauses were relatively short and fairly
      constant in duration as the ratio increased; pause durations increased rapidly
      near the end of a session. The relation between the average number of completed
      ratios and step size was described well by a power function [y = b(xa), in which
      y represents the average number of completed ratios, x represents the step size,
      and a and b are fitted parameters]. Increasing the break-point criterion from 5
      to 15 min resulted in increased values of b, whereas parameter a was relatively
      unaffected and was close to -1 (consistent with the lack of effect of step size
      on breaking point). This function also provided an excellent description of data
      drawn from previous reports.

PMID- 9768505
TI  - Effects of variable-interval value and amount of training on stimulus
      generalization.
AB  - In Experiment 1 pigeons pecked a key that was illuminated with a 501-nm light and
      obtained food by doing so according to a variable-interval (VI) schedule of
      reinforcement, the mean value of which differed across groups: either 30 s, 120
      s, or 240 s. The pigeons in all three groups were trained for 10 50-min sessions.
      Generalization testing was conducted in extinction with different wavelengths of
      light. Absolute and relative generalization gradients were similar in shape for
      the three groups. Experiment 2 was a systematic replication of Experiment 1 using
      line orientation as the stimulus dimension and a mean VI value of either 30 s or
      240 s. Again, gradients of generalization were similar for the two groups. In
      Experiment 3 pigeons pecked a key that was illuminated with a 501-nm light and
      obtained food reinforcers according to either a VI 30-s or a 240-s schedule.
      Training continued until response rates stabilized (> 30 sessions). For subjects
      trained with the 30-s schedule, generalization gradients were virtually identical
      regardless of whether training was for 10 sessions (Experiment 1) or until
      response rates stabilized. For subjects trained with the VI 240-s schedule,
      absolute generalization gradients for subjects trained to stability were
      displaced upward relative to gradients for subjects trained for only 10 sessions
      (Experiment 1), and relative generalization gradients were slightly flatter.
      These results indicate that the shape of a generalization gradient does not
      necessarily depend on the rate of reinforcement during 10-session single-stimulus
      training but that the effects of prolonged training on stimulus generalization
      may be schedule dependent.

PMID- 9768506
TI  - Ratio size and cocaine concentration effects on oral cocaine-reinforced behavior.
AB  - Monkeys were given a choice between cocaine solutions and water under concurrent
      fixed-ratio reinforcement schedules. The operant response was spout contact. Six
      rhesus monkeys served as subjects. The cocaine concentration was varied from
      0.0125 to 0.8 mg/ml, and the fixed-ratio value was varied from 8 to 128. Cocaine
      maintained higher response rates than did water over a wide range of conditions.
      Response rate and number of cocaine deliveries per session were inverted U-shaped
      functions of concentration. These functions were shifted to the right as the
      fixed ratio was increased. The number of cocaine deliveries was more persistent
      as fixed-ratio value was increased when the unit dose was larger rather than
      smaller. Cocaine consumption was analyzed as a function of unit price (fixed
      ratio value divided by cocaine concentration), and unit price accounted for
      between 77% and 92% of the variance in cocaine consumption for individual
      monkeys. The current data support the claim that a drug's reinforcing effects
      increase directly with dose and underscore the need to gather parametric data
      when examining the effects of experimental manipulations on a drug-reinforced
      baseline.

PMID- 9768507
TI  - Mental rotation and temporal contingencies.
AB  - A task that requires subjects to determine whether two forms of the same shape,
      but in different orientations, are mirror images or identical except for
      orientation is called a handedness recognition task. Subjects' reaction times
      (RT) on this task are consistently related to the angular disparity (termed
      alpha) between the two presented forms. This pattern of data has been interpreted
      to indicate that subjects solve the task by imagining that one of the forms
      rotates into the orientation of the other (termed mental rotation). The speed
      with which one imagines one of the forms rotating has been widely considered a
      fixed capability of the individual, and thus immune to the effect of
      contingencies. We present an experiment that assesses the effects of temporal
      contingencies in a handedness recognition task on the slope of the function RT =
      f(alpha). The data indicate that the slope of this function can come under the
      control of temporal contingencies.

PMID- 9768508
TI  - Superresolution and convergence properties of the expectation-maximization
      algorithm for maximum-likelihood deconvolution of incoherent images.
AB  - Computational optical-sectioning microscopy with a nonconfocal microscope is
      fundamentally limited because the optical transfer function, the Fourier
      transform of the point-spread function, is exactly zero over a conic region of
      the spatial-frequency domain. Because of this missing cone of optical
      information, images are potentially artifactual. To overcome this limitation,
      superresolution, in the sense of band extrapolation, is necessary. I present a
      frequency-domain analysis of the expectation-maximization algorithm for maximum
      likelihood image estimation that shows how the algorithm achieves this band
      extrapolation. This analysis gives the theoretical absolute bandwidth of the
      restored image; however, this absolute value may not be realistic in many cases.
      Then a second analysis is presented that assumes a Gaussian point-spread function
      and a specimen function and shows more realistic behavior of the algorithm and
      demonstrates some of its properties. Experimental results on the superresolving
      capability of the algorithm are also presented.

PMID- 9768509
TI  - Total least-squares reconstruction with wavelets for optical tomography.
AB  - In a previous paper [Zhu et al., J. Opt. Soc. Am. A 14, 799 (1997)] an iterative
      algorithm for obtaining the total least-squares (TLS) solution of a linear system
      based on the Rayleigh quotient formulation was presented. Here we derive what to
      our knowledge are the first statistical properties of this solution. It is shown
      that the Rayleigh-quotient-form TLS (RQF-TLS) estimator is equivalent to the
      maximum-likelihood estimator when noise terms in both data and operator elements
      are independent and identically distributed Gaussian. A perturbation analysis of
      the RQF-TLS solution is derived, and from it the mean square error of the RQF-TLS
      solution is obtained in closed form, which is valid at small noise levels. We
      then present a wavelet-based multiresolution scheme for obtaining the TLS
      solution. This method was employed with a multigrid algorithm to solve the linear
      perturbation equation encountered in optical tomography. Results from numerical
      simulations show that this method requires substantially less computation than
      the previously reported one-grid TLS algorithm. The method also allows one to
      identify regions of interest quickly from a coarse-level reconstruction and
      restrict the reconstruction in the following fine resolutions to those regions.
      Finally, the method is less sensitive to noise than the one-grid TLS and
      multigrid least-squares algorithms.

PMID- 9768510
TI  - Scattering of electromagnetic waves from dense distributions of spheroidal
      particles based on Monte Carlo simulations.
AB  - In a dense discrete random medium, the propagation and scattering of waves are
      affected not only by the individual properties of the particles such as size,
      shape, and permittivity, but also by group properties such as the statistics of
      relative particle positions and relative orientations. We use Monte Carlo
      simulations to investigate the interactions of electromagnetic waves with a dense
      medium consisting of spheroidal particles for cases of random orientation and for
      cases of aligned orientation. A shuffling process is used to generate the
      positions of densely packed spheroids. Multiple-scattering equations are
      formulated by means of the volume integral equation and are solved numerically.
      The scattering results are averaged over realizations. Numerical results are
      presented for the extinction rates and the phase matrices. Salient features of
      the numerical results indicate that (1) the extinction rates of densely packed
      small spheroids are smaller than those of independent scattering; (2) for aligned
      spheroids, the extinction rates are polarization dependent; and (3) the co
      polarized part of the phase matrix for densely packed spheroids is smaller than
      that of independent scatering, while the cross-polarized part is larger than that
      for independent scattering. This means that the ratio of cross-polarization to co
      polarization is significantly higher than that of independent scattering.

PMID- 9768511
TI  - Fourier transform ion cyclotron resonance mass spectrometry: a primer.
AB  - This review offers an introduction to the principles and generic applications of
      FT-ICR mass spectrometry, directed to readers with no prior experience with the
      technique. We are able to explain the fundamental FT-ICR phenomena from a
      simplified theoretical treatment of ion behavior in idealized magnetic and
      electric fields. The effects of trapping voltage, trap size and shape, and other
      nonidealities are manifested mainly as perturbations that preserve the idealized
      ion behavior modified by appropriate numerical correction factors. Topics
      include: effect of ion mass, charge, magnetic field, and trapping voltage on ion
      cyclotron frequency; excitation and detection of ICR signals; mass calibration;
      mass resolving power and mass accuracy; upper mass limit(s); dynamic range;
      detection limit, strategies for mass and energy selection for MSn; ion
      axialization, cooling, and remeasurement; and means for guiding externally formed
      ions into the ion trap. The relation of FT-ICR MS to other types of Fourier
      transform spectroscopy and to the Paul (quadrupole) ion trap is described. The
      article concludes with selected applications, an appendix listing accurate
      fundamental constants needed for ultrahigh-precision analysis, and an annotated
      list of selected reviews and primary source publications that describe in further
      detail various FT-ICR MS techniques and applications.

PMID- 9768512
TI  - A secretory cellulose-binding protein cDNA cloned from the root-knot nematode
      (Meloidogyne incognita).
AB  - A cDNA encoding a secretory cellulose-binding protein was cloned from the root
      knot nematode (Meloidogyne incognita) with RNA fingerprinting. The putative full
      length cDNA, named Mi-cpb-1, encoded a 203 amino acid protein containing an N
      terminal secretion signal peptide. The C-terminal sequence of the putative MI-CBP
      1 was similar to a bacterial-type cellulose-binding domain, whereas the N
      terminal sequence did not show significant similarity to any proteins in data
      bases. Recombinant MI-CBP-1 lacked cellulase activity, but bound to cellulose and
      plant cell walls. In Southern blot hybridization, Mi-cbp-1 hybridized with
      genomic DNA from M. incognita, M. arenaria, and M. javanica, but not M. hapla,
      Heterodera glycines, or Caenorhabditis elegans. Polyclonal antibodies raised
      against recombinant MI-CBP-1 strongly labeled secretory granules in subventral
      gland cells of second-stage juveniles in indirect immunofluorescence microscopy.
      Enzyme-linked immunosorbent assay detection of MI-CBP-1 in stylet secretions of
      second-stage juveniles with the polyclonal antibodies indicated MI-CBP-1 could be
      secreted through the nematodes' stylet, suggesting that the cellulose-binding
      protein may have a role in pathogenesis.

PMID- 9768513
TI  - nec1, a gene conferring a necrogenic phenotype, is conserved in plant-pathogenic
      Streptomyces spp. and linked to a transposase pseudogene.
AB  - We are investigating the genetic basis for, and evolution of, plant pathogenicity
      in Streptomyces spp. The plant-pathogenic species S. scabies, S. acidiscabies,
      and S. turgidiscabies cause the scab disease of potato and produce the
      phytotoxins, thaxtomins. Forty-three Streptomyces strains representing the three
      species were evaluated; all thaxtomin A-producing Streptomyces strains were
      pathogenic on potato tubers and all but one hybridized to nec1 and ORFtnp, two
      genes previously cloned from S. scabies ATCC 41973. nec1 confers a pathogenic
      phenotype on S. lividans TK24, a nonpathogen, and ORFtnp is a transposase
      pseudogene located 5' to nec1. The eight nonpathogenic strains tested neither
      produced thaxtomin A nor hybridized to nec1. ORFtnp and nec1 occurred on a single
      PvuII restriction fragment in all thaxtomin A-producing Streptomyces strains. The
      nucleotide sequences of the homologs of nec1 and ORFtnp from two pathogenic
      strains each of S. scabies, S. acidiscabies, and S. turgidiscabies were
      identical; oligonucleotide primers specific to this gene amplified homologs from
      all strains that hybridized to nec1. We propose that nec1 and ORFtnp have been
      horizontally mobilized from S. scabies to S. acidiscabies and S. turgidiscabies,
      and that nec1 is involved in pathogenicity and physically linked to the thaxtomin
      A biosynthetic genes.

PMID- 9768514
TI  - The isolation and mapping of disease resistance gene analogs in maize.
AB  - Many of the plant disease resistance genes that have been isolated encode
      proteins with a putative nucleotide binding site and leucine-rich repeats (NBS
      LRR resistance genes). Oligonucleotide primers based on conserved motifs in and
      around the NBS of known NBS-LRR resistance proteins were used to amplify
      sequences from maize genomic DNA by polymerase chain reaction (PCR). Eleven
      classes of non-cross-hybridizing sequences were obtained that had predicted
      products with high levels of amino acid identity to NBS-LRR resistance proteins.
      These maize resistance gene analogs (RGAs) and one RGA clone obtained previously
      from wheat were used as probes to map 20 restriction fragment length polymorphism
      (RFLP) loci in maize. Some RFLPs were shown to map to genomic regions containing
      virus and fungus resistance genes. Perfect cosegregation was observed between RGA
      loci and the rust resistance loci rp1 and rp3. The RGA probe associated with rp1
      also detected deletion events in several rp1 mutants. These data strongly suggest
      that some of the RGA clones may hybridize to resistance genes.

PMID- 9768515
TI  - Sulfation of nod factors via nodHPQ is nodD independent in Rhizobium tropici
      CIAT899.
AB  - A cosmid from the Rhizobium tropici CIAT899 symbiotic plasmid, containing most of
      the nodulation genes described in this strain, has been isolated. Although this
      cosmid does not carry a nodD gene, it confers ability to heterologous Rhizobium
      spp. to nodulate R. tropici hosts (Phaseolus vulgaris, Macroptilium
      atropurpureum, and Leucaena leucocephala). The observed phenotype is due to
      constitutive expression of the nodABCSUIJ operon, which has lost its regulatory
      region and is expressed from a promoter present in the cloning vector. Thin-layer
      chromatography (TLC) analysis of the Nod factors produced by this construction
      shows that it is still capable of synthesizing sulfated compounds, suggesting
      that the nodHPQ genes are organized as an operon that is transcribed in a nodD
      independent manner and is not regulated by flavonoids.

PMID- 9768518
TI  - The endopolygalacturonase gene Bcpg1 is required for full virulence of Botrytis
      cinerea.
AB  - Botrytis cinerea, a fungus that causes diseases in over 200 plant species,
      secretes a number of endopolygalacturonases that have been suggested to be
      involved in pathogenesis. However, so far the corresponding genes have not been
      isolated from this fungus. We cloned Bcpg1, encoding endopolygalacturonase, with
      the pgaII gene from Aspergillus niger as a heterologous probe. The Bcpg1 gene is
      expressed to similar levels in liquid cultures of B. cinerea containing either 1%
      polygalacturonic acid or 1% sucrose, and is expressed during infection of tomato
      leaves. The Bcpg1 gene was eliminated by partial gene replacement, and the
      resulting mutants were tested for virulence on tomato leaves and fruits, as well
      as on apple fruits. Although the mutants were still pathogenic and displayed
      similar primary infections when compared with control strains, a significant
      decrease in secondary infection, i.e., growth of the lesion beyond the
      inoculation spot, was observed on all three host tissues. These results indicate
      that the Bcpg1 gene is required for full virulence.

PMID- 9768520
TI  - Starving tumors of their lifeblood.

PMID- 9768521
TI  - Bloodless testing.

PMID- 9768522
TI  - Designer estrogens.

PMID- 9768523
TI  - Review article: the use of biotherapeutic agents in the prevention and treatment
      of gastrointestinal disease.
AB  - There is presently a lack of well conducted clinical trials demonstrating any
      significant benefits of probiotics in humans. With the exception of diarrhoea due
      to rotavirus infection in children there is little evidence from randomized,
      double-blind, placebo-controlled studies that bacterial probiotics have a
      significant beneficial action in preventing diarrhoea of any cause. The yeast
      Saccharomyces boulardii has been shown to be of benefit in the prevention of
      antibiotic-associated diarrhoea but not in preventing infection with Clostridium
      difficile. S. boulardii may also be of benefit in preventing relapse of C.
      difficile infection. Because of the simplicity of in vitro systems and some
      animal models, beneficial characteristics of probiotics such as the ability of
      bacteria to bind to epithelial surfaces are not always transferable to humans.
      Thus any postulated benefit from consumption of probiotic bacteria should only be
      accepted as fact after testing in clinical studies. This review outlines our
      present knowledge of the mode of action of probiotics and presents the data from
      clinical trials on their use.

PMID- 9768524
TI  - Review article: one-week clarithromycin triple therapy regimens for eradication
      of Helicobacter pylori.
AB  - BACKGROUND: One-week triple therapies have been endorsed as the treatment
      regimens of choice for eradication of Helicobacter pylori infection. Those that
      include clarithromycin appear to be the most effective. AIM: To review reports of
      triple therapies that include clarithromycin. METHODS: Reports were identified
      from the literature to May 1998. The variation between study designs prevents a
      formal meta-analysis. A measure of the relative efficacies of regimens has,
      however, been gained by comparison and by pooling of intention-to-treat
      eradication rates. RESULTS: One hundred and ninety-two studies were identified
      which included 264 treatment arms of a 1-week triple therapy composed of
      clarithromycin with amoxycillin or a nitroimidazole (metronidazole or
      tinidazole), and either ranitidine bismuth citrate or a proton pump inhibitor
      (omeprazole, lansoprazole or pantoprazole). From reports of these studies, an
      intention-to-treat H. pylori eradication rate could be determined from 210
      treatment arms of 151 studies. CONCLUSIONS: There is little to choose between the
      efficacies of 1-week clarithromycin-based triple therapy eradication regimens.
      However, those comprising clarithromycin, a nitroimidazole and either ranitidine
      bismuth citrate or a high dose of omeprazole are, in general, the most effective.
      Against antibiotic-resistant strains of H. pylori, regimens including ranitidine
      bismuth citrate may be more effective than those including a proton pump
      inhibitor.

PMID- 9768525
TI  - Idiopathic bile acid malabsorption: qualitative and quantitative clinical
      features and response to cholestyramine.
AB  - BACKGROUND: Idiopathic bile acid malabsorption is a poorly recognized cause of
      chronic diarrhoea. The SeHCAT (75Selenium HomotauroCholic Acid Test) can
      accurately diagnose this condition. AIM: To identify patients with idiopathic
      bile acid malabsorption, to describe their clinical features, both qualitatively
      and quantitatively, and to assess the response to cholestyramine. METHOD:
      Idiopathic bile acid malabsorption was considered in all patients complaining of
      chronic diarrhoea. They were included in the study if their SeHCATs were positive
      (< 15% retention) and secondary causes of bile acid malabsorption were excluded.
      The response to therapy with cholestyramine was assessed. RESULTS: Nine patients
      were diagnosed with idiopathic bile acid malabsorption (median SeHCAT retention
      8%, range 3-12.6). Their median daily faecal weight was 285 g (range 85-676) and
      median faecal fat output was 17 mmol/24 h (range 8.3-38.8). Six patients had an
      immediate response to cholestyramine. There was a marked reduction in stool
      frequency (median stool frequency pre-treatment 5/day vs. 2/day post-treatment, P
      = 0.03). Five patients had large volume diarrhoea (faecal weight > 200 g/day) and
      three had steatorrhoea. CONCLUSIONS: Idiopathic bile acid malabsorption, once
      suspected, especially by documenting true 'large volume' watery diarrhoea or
      steatorrhoea, is easily diagnosed and response to therapy is often very good.
      There is often a previous history of gastrointestinal infection and this
      condition should be considered in patients with chronic diarrhoea of undetermined
      origin, especially before they are labelled as having irritable bowel syndrome.

PMID- 9768526
TI  - Ferric trimaltol corrects iron deficiency anaemia in patients intolerant of iron.
AB  - BACKGROUND: Oral iron supplements, which are usually in the form of ferrous
      (Fe2+) salts, are toxic to the gastrointestinal mucosa, and so intolerance is
      common, resulting in poor compliance and failure of treatment. The sugar
      derivative maltol strongly chelates iron, rendering it available for absorption
      and stabilized in the less toxic ferric (Fe3+) form. AIM: To test whether ferric
      trimaltol could correct iron deficiency anaemia in patients intolerant of ferrous
      sulphate. METHODS: Twenty-three patients were recruited from gastroenterology
      clinics, of whom 1 5 had inflammatory bowel disease, a group often difficult to
      treat with oral iron. Patients with iron deficiency anaemia and documented
      intolerance to ferrous sulphate were given 3 months of treatment with ferric
      trimaltol. RESULTS: Nineteen of 23 patients completed the treatment and anaemia
      was fully corrected in 14 of these, mean haemoglobin increased from 106 +/- 15 to
      126 +/- 16 g/L, and there was a particularly low incidence of side-effects. Of 11
      patients with inflammatory bowel disease who completed the study, nine fully
      corrected their anaemia. CONCLUSION: The results demonstrate that in patients
      intolerant of ferrous compounds, ferric trimaltol corrects iron deficiency and
      has a low incidence of side-effects.

PMID- 9768527
TI  - Effect of alosetron on responses to colonic distension in patients with irritable
      bowel syndrome.
AB  - BACKGROUND: Visceral hypersensitivity plays a major role in the pathophysiology
      of irritable bowel syndrome, as shown by balloon distension studies. 5-HT3
      receptors on afferent nerves may modulate visceral sensitivity and be the target
      of new treatments for irritable bowel syndrome. AIM: To evaluate the effects of
      alosetron, a potent and selective 5-HT3 antagonist, on the perception of colonic
      distension by patients with irritable bowel syndrome, and on the colonic
      compliance to distension with a barostat. METHODS: Twenty-five irritable bowel
      syndrome patients were included in a randomized double-blind parallel group
      trial; data were available for 22 (Rome criteria; 48 +/- 11 years: 13 men and
      nine women). Patients were treated for 7 days with placebo (n = 6), alosetron
      0.25 mg b.d. (n = 8) or alosetron 4 mg b.d. (n = 8). On day 6, a barostat bag was
      placed in the left colon. On day 7, after an overnight fast, isobaric phasic
      distensions were performed (4 mmHg steps, 5 min) up to the step triggering a
      sensation of abdominal pain. RESULTS: Groups were comparable at inclusion (age,
      sex, symptoms, bowel habits). There were no differences between treatment groups
      in pressure recorded within the bag at the time of first sensation of abdominal
      pain. However, bag volumes were significantly increased. At the first sensation
      threshold, median volume differences of 61 mL and 90 mL (P = 0.028) were recorded
      with alosetron 0.25 mg b.d. and 4 mg b.d., respectively. At the threshold of
      abdominal pain, these differences were 71 mL (P = 0.039) and 84 mL (P = 0.017).
      Colonic compliance increased from 5.9 mL/mmHg on placebo to 7.6 mL/mmHg on
      alosetron 0.25 mg b.d. and to 9.8 mL/mmHg (P = 0.034) on alosetron 4 mg b.d.
      CONCLUSION: Alosetron increases the compliance of the colon to distension, and
      could thereby contribute to changes in perception of colonic distension and
      improvement in the symptoms of irritable bowel syndrome.

PMID- 9768528
TI  - Helicobacter pylori-positive peptic ulcer patients do not adapt to aspirin.
AB  - BACKGROUND: Recent studies indicate that eradication of Helicobacter pylori might
      prevent peptic ulcer formation in patients treated with non-steroidal anti
      inflammatory drugs (NSAIDs). On the other hand, gastric adaptation after repeated
      exposures to aspirin (ASA) is well documented but the influence of H. pylori on
      this process remains to be elucidated. AIM: To compare gastric damage and
      adaptation following repeated exposures to ASA in a group of patients with H.
      pylori infection, before and after eradication of the bacterium, and in H. pylori
      negative controls. METHODS: Eight healthy volunteers without H. pylori infection
      and eight patients with duodenal ulcer (DU) history and H. pylori infection
      before and after H. pylori eradication were given ASA 2 g/day for a period of 14
      days. Mucosal damage was evaluated by endoscopy and histology of biopsy samples.
      Gastric microbleeding, DNA synthesis in the gastric mucosa and mucosal
      expression, as well as luminal content of transforming growth factor-alpha
      (TGFalpha) were determined on days 0, 3, 7 and 14 of the ASA course. RESULTS: In
      all patients aspirin-induced gastric damage reached a maximum on day 3. In H.
      pylori-positive patients, this damage was maintained at a similar level up to day
      14, whereas in H. pylori-negative controls and H. pylori-eradicated patients this
      damage significantly lessened on day 14 and was accompanied by elevated DNA
      synthesis as well as increased mucosal expression and luminal release of
      TGFalpha.

PMID- 9768529
TI  - Pantoprazole 20 mg is effective for relief of symptoms and healing of lesions in
      mild reflux oesophagitis.
AB  - AIM: To investigate the efficacy of a low dose of pantoprazole, a gastric proton
      pump inhibitor, for the relief of symptoms and healing of lesions in mild gastro
      oesophageal reflux disease (GERD), and to compare it with the efficacy of
      ranitidine. METHODS: Patients with endoscopically established GERD (Stage I,
      Savary-Miller classification) were enrolled into a randomized, double-blind,
      parallel-group and multicentre study (intention-to-treat n = 209, age range 19-82
      years). They were treated once daily with oral pantoprazole 20 mg or ranitidine
      300 mg, for up to 8 weeks. End-point parameters included relief of symptoms
      (heartburn, acid regurgitation, pain on swallowing) and the healing of GERD
      lesions. Relief from symptoms was assessed after 2 and 4 weeks, and
      endoscopically confirmed healing of lesions after 4 and 8 weeks. RESULTS: The
      proportion of patients reporting complete relief from symptoms after 2 weeks was
      greater in the pantoprazole than in the ranitidine group (69 vs. 48%, P < 0.01),
      with further improvements seen in the pantoprazole group after 4 weeks (80 vs.
      65%, P < 0.05, Cochran-Mantel/Haenszel test). Healing of lesions was confirmed in
      70/87 (80%) patients after 4 weeks (pantoprazole group), as compared with 55/86
      (64%) patients (ranitidine group) (P < 0.05, per protocol population); after 8
      weeks the respective results were 78/87 (90%) and 63/86 (73%) patients (P <
      0.01). Both study medications were well tolerated. CONCLUSION: Low-dose
      pantoprazole (20 mg) is clinically superior to ranitidine (300 mg) in providing
      fast relief from symptoms and healing of lesions in patients with mild GERD.

PMID- 9768530
TI  - H2-antagonist maintenance therapy versus Helicobacter pylori eradication in
      patients with chronic duodenal ulcer disease: a prospective study.
AB  - BACKGROUND: Few outcome studies directly compare Helicobacter pylori eradication
      therapy with maintenance H2-antagonist therapy in duodenal ulcer disease. AIM: To
      examine prospectively the efficacy of H. pylori eradication therapy with
      ranitidine maintenance therapy over 1 year in patients with confirmed chronic
      duodenal ulcer. METHODS: One hundred and nineteen patients with active H. pylori
      infection were randomized to receive ranitidine, 150 mg/day initially (58
      patients), or omeprazole, 40 mg/day, amoxycillin 2 g/day and metronidazole 1.2
      g/day for 14 days, or omeprazole 40 mg/day and clarithromycin 1.5 g/day, for 14
      days (if penicillin-allergic). Symptoms were assessed using the Gastrointestinal
      System Rating Scale (GSRS) and SF36 quality of life index. RESULTS: 13C urea
      breath testing confirmed overall treatment success in 100% of patients (58/58)
      per protocol and 95.1% (58/61) on an intention-to-treat basis. At 4 and 12 months
      there were no differences in any GSRS symptoms between treatment groups. SF36
      analysis showed a perceived health improvement at 4 and 12 months in patients who
      received H. pylori eradication. However, despite successful H. pylori
      eradication, one-fifth of patients still required antisecretory therapy.
      CONCLUSION: Following successful H. pylori eradication, chronic duodenal ulcer
      patients were at least as well symptomatically as when taking maintenance
      ranitidine. They perceived that their health had improved, but a subgroup was
      still acid-suppression dependent.

PMID- 9768531
TI  - Helicobacter pylori eradication and ulcer healing with daily lansoprazole, plus 1
      or 2 weeks co-therapy with amoxycillin and clarithromycin.
AB  - BACKGROUND: Proton pump inhibitor based combination therapy is one standard
      strategy for Helicobacter pylori eradication. AIM: To compare the eradication and
      duodenal ulcer healing efficacy of two 2-week, single dose, lansoprazole based
      combination therapies. METHODS: Healthy adult patients with endoscopically
      confirmed, H. pylori associated duodenal ulcer disease (3 mm > ulcer < 20 mm)
      were eligible for the study. All patients received a 14 day course of
      lansoprazole 30 mg o.m., and were randomized to receive either 7 or 14 days of
      amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. Patients were endoscoped at
      entry and 14-17 days later. Symptomatic, unhealed patients received a further 14
      days of therapy with lansoprazole 30 mg o.m. Eradication was confirmed a minimum
      of 28 days after cessation of all therapy by urease reaction and histological
      assessment of gastric body and antral biopsies (three biopsies each site).
      RESULTS: Sixty-two patients were randomized to a treatment arm, of which 58 could
      be included in an intention-to-treat and key-point-available analysis. H. pylori
      eradication rates were identical, at 93% (95% CI: 73-98% (1 week), 78-99% (2
      week)). In the combined group, all but 13 ulcers were healed at 2 weeks; six
      required further therapy because of symptoms, while six of the seven asymptomatic
      patients went on to heal. CONCLUSION: An eradication regimen, based on a 2-week
      course of single dose lansoprazole with 1 week of antibiotic co-therapy, is
      effective in eradicating H. pylori, while the 2 weeks of acid suppression is
      usually effective in duodenal ulcer healing.

PMID- 9768532
TI  - Low rate of emergence of clarithromycin-resistant Helicobacter pylori with
      amoxycillin co-therapy.
AB  - BACKGROUND: Patients with persistent Helicobacter pylori infection following
      treatment with clarithromycin or omeprazole plus clarithromycin often develop
      clarithromycin resistance. AIM: To assess pre- and post-treatment antibiotic
      resistance in three double-blind trials of triple therapy with omeprazole,
      amoxycillin and clarithromycin. METHODS: Patients with H. pylori and duodenal
      ulcer (studies 1 and 2) or history of duodenal ulcer (study 3) were randomly
      assigned to 10 day courses of omeprazole 20 mg b.d., amoxycillin 1 g b.d. and
      clarithromycin 500 mg b.d. (OAC) or placebo, amoxycillin 1 g b.d. and
      clarithromycin 500 mg b.d. (AC). Endoscopy was performed at baseline and 4 weeks
      after completion of therapy in studies 1 and 2, and at 4-6 weeks after therapy in
      study 3. At baseline, H. pylori was diagnosed by CLO test with confirmation by
      histology, or by culture. Eradication was defined as no positive biopsy test and
      > or = 2 negative tests. Susceptibility testing was performed using the Etest.
      RESULTS: In the 91 patients with pre-treatment susceptible isolates who had
      persistent infection after AC, 10 developed resistance, eight had intermediate
      susceptibility and 73 continued to have clarithromycin-susceptible H. pylori
      isolates. In the 10 patients with pre-treatment susceptible isolates who had
      persistent infection after OAC, three developed clarithromycin resistance and
      seven still had susceptible isolates. CONCLUSIONS: Use of amoxycillin co-therapy
      results in a low rate of clarithromycin resistance developing in patients with
      persistent H. pylori infection following therapy with a clarithromycin-containing
      regimen.

PMID- 9768533
TI  - Continuous treatment with omeprazole 20 mg daily for up to 6 years in Barrett's
      oesophagus.
AB  - BACKGROUND: Because of the malignant potential of Barrett's oesophagus, an aim of
      treatment is to cause the columnar epithelium to regress. A logical approach is
      to decrease acid reflux which is an important aetiological factor in Barrett's
      oesophagus. Treatment with omeprazole 20-80 mg over 1-3 years has yielded
      conflicting but largely disappointing results. AIM: To determine if treatment of
      Barrett's oesophagus with omeprazole 20 mg daily for up to 6 years can cause
      regression of the Barrett's epithelium. PATIENTS AND METHODS: Forty-seven
      patients with Barrett's oesophagus were treated in an open prospective study.
      Nine patients were treated for 2 years, 12 for 3 years, 10 for 4 years, eight for
      5 years and eight for 6 years. Patients were endoscoped at 1-2-year intervals and
      endoscoped at the end of the treatment period. RESULTS: No significant shortening
      of the length of the Barrett's segment was seen during any treatment period,
      although omeprazole controlled reflux symptoms and was well tolerated.
      Macroscopic squamous islands appeared in 55% of patients, mostly in the first 2-3
      years although in five patients they appeared later in treatment. CONCLUSION:
      Treatment of Barrett's oesophagus with omeprazole 20 mg daily for periods of up
      to 6 years did not cause regression in the length of the Barrett's segment, but
      it did lead in over half of the patients to partial re-epithelialization in the
      form of squamous islands.

PMID- 9768534
TI  - The effect of healing oesophagitis on oesophageal motor function as determined by
      oesophageal scintigraphy and ambulatory oesophageal motility/pH monitoring.
AB  - BACKGROUND: Oesophagitis has been shown by standard manometry to be associated
      with impaired oesophageal motility, but it remains unclear if this abnormality
      improves with healing of oesophagitis. AIM: To determine if healing of
      oesophagitis improves oesophageal motility using solid bolus oesophageal transit
      scintigraphy and combined ambulatory oesophageal motility/pH monitoring. METHODS:
      Patients with grade II-III oesophagitis underwent ambulatory motility/pH
      monitoring (using a Konigsberg catheter with four pressure transducers at 5 cm
      intervals) and solid bolus scintigraphy before and after treatment with
      omeprazole 20 mg b.d. for 8-14 weeks. RESULTS: Three (11%) of the 28 patients
      failed to heal. Initial scintigraphy was abnormal in 18 (67%) of 27 patients (one
      refused scintigraphy). Twenty-three of the 25 healed patients had repeat studies
      showing no significant change in the number which were abnormal (16 (64%), P =
      1.0) or the overall oesophageal transit time (P = 0.65). Due to intolerance of
      the technique, only 11 patients had ambulatory motility/pH performed both before
      and after healing, giving the study 90% power to detect a 5 mmHg increase in
      peristaltic amplitude. No significant improvement was seen in any motility or pH
      parameter after healing of oesophagitis. CONCLUSION: Analysis of oesophageal
      motility showed no improvement in peristaltic activity after healing of
      oesophagitis, suggesting that the abnormal motility is either a primary disorder
      or an irreversible consequence of mucosal damage.

PMID- 9768535
TI  - On-demand treatment of gastro-oesophageal reflux symptoms: a comparison of
      ranitidine 75 mg with cimetidine 200 mg or placebo.
AB  - AIM: To compare the effects of ranitidine 75 mg with those of either cimetidine
      200 mg or placebo given on demand for relief of typical symptoms of gastro
      oesophageal reflux disease during a 15-day period. METHODS: A total of 1336
      patients (aged > or = 18 years) with heartburn episodes were recruited and
      randomly assigned to a ranitidine 75 mg, cimetidine 200 mg or placebo group.
      Depending on the occurrence or persistence of heartburn, treatment was
      administered as required up to three times daily, with at least 2 h between drug
      doses. Antacids were allowed as rescue medication if symptoms persisted for at
      least 2 h after the third medication on any given day. The primary end-point was
      defined as the proportion of patients with relief of at least 75% of heartburn
      episodes during the study period (i.e. relief occurring within 2 h after drug
      ingestion and lasting for at least 5 h). RESULTS: Analysis was performed in an
      intention-to-treat population comprising 504 subjects in the ranitidine group,
      515 in the cimetidine group and 270 in the placebo group. Primary end-point
      success rates were 41, 38 and 28%, respectively, for the three groups (P < 0.001
      for ranitidine vs. placebo, P = 0.274 for ranitidine vs. cimetidine). Ranitidine
      75 mg was significantly more effective than placebo in providing overall
      heartburn relief (P < 0.001). The differences between the ranitidine and
      cimetidine groups were not significant, except for a greater reduction in
      heartburn frequency in the ranitidine group at the end of the study period (P <
      0.05). Drug dose was lower and less rescue medication was used in the ranitidine
      group than the placebo group. The three treatment groups did not differ in terms
      of tolerability. CONCLUSION: On-demand ranitidine 75 mg or cimetidine 200 mg are
      safe and effective treatment for reflux-related symptoms.

PMID- 9768536
TI  - Estimating the cost of lost productivity in dyspepsia.
AB  - BACKGROUND: In the field of gastrointestinal disease, productivity costs are
      highly relevant because work loss is substantial in dyspeptic patients.
      Productivity costs are normally calculated by multiplying days absent valued by
      gross earnings. This, however, might lead to an overestimation. AIM: To use a
      conservative approach to calculating productivity costs, taking absence
      compensating mechanisms into account. METHODS: Patients who visited their general
      practitioner for the first time with dyspeptic complaints and patients who were
      known to have persistent dyspeptic complaints were enrolled in two studies. In
      total, 136 patients completed a questionnaire about their employment situation,
      absence from work and absence compensating mechanisms. RESULTS: Sixty-six of the
      respondents had a paid job, of which 25 (38%) reported absence from work during
      the previous 4 weeks (average 3.0 days, 1.9 days related to dyspeptic
      complaints). More than 50% of the employed respondents answered that absence
      could be compensated for by colleagues, and only in 8% of the cases was absence
      compensated for by overtime. Using our conservative approach, only one-quarter of
      the productivity costs remained, compared to the current approach of valuing each
      day absent as a loss of productivity. CONCLUSIONS: We suggest using both the
      current and the conservative approaches, analogous to the principles of
      sensitivity analysis, to avoid overestimation of productivity costs.

PMID- 9768537
TI  - Experimental colitis induced by dextran sulphate sodium in mice: beneficial
      effects of sulphasalazine and olsalazine.
AB  - BACKGROUND: Animal models of inflammatory bowel disease are artificial and more
      or less representative of human disease. However, the dextran sulphate sodium
      (DSS) induced intestinal inflammation model has recently been shown to fulfil
      some pathological criteria for an adequate experimental model. AIM: To determine
      whether this form of experimental intestinal inflammation responds to established
      therapy used for human inflammatory bowel disease. METHODS: DSS was used to
      induce intestinal inflammation in conventional Balb/c mice and athymic nu/nu CD
      1(BR) mice, and the well-documented 5-aminosalicylic acid (5-ASA) based
      anticolitis drugs sulphasalazine (SASP) and olsalazine (OLZ) were used to study
      therapeutic effects. Parameters which have been shown to reflect DSS-induced
      intestinal inflammation (body weight, colon length, spleen weight, diarrhoea, and
      rectal bleeding) were measured in the Balb/c mice. RESULTS: Significant
      amelioration was seen on these parameters after different treatment protocols.
      Survival in nu/nu CD-1 mice was studied, and after 16 days a death rate of 50%
      was noted in the DSS group. SASP (100 mg/kg/day) and OLZ (50 mg/kg/day)
      significantly prolonged the survival to 29 and 38 days, respectively. SASP and
      OLZ showed a dose-dependent effect in the range between 10 and 100 mg/kg/day,
      doses closely corresponding to those used in humans. CONCLUSIONS: SASP and OLZ
      are able to ameliorate the DSS-induced intestinal inflammation. The dose-response
      patterns suggested that the active therapeutic moiety for the two drugs appears
      to be mainly the liberated 5-ASA molecule.

PMID- 9768538
TI  - The role of GABA(A) receptors in the acute and chronic effects of ethanol.
AB  - GABA(A) receptors are sensitive to ethanol in distinct brain regions and are
      clearly involved in the acute actions of ethanol, ethanol tolerance, ethanol
      dependence and ethanol self-administration. Data from a variety of perspectives
      such as molecular, cellular and behavioral analysis have elucidated the role of
      GABA(A) receptors in these processes. GABA(A) receptor activation mediates many
      of the behavioral effects of ethanol including motor incoordination, anxiolysis
      and sedation. The actions of ethanol at GABA(A) receptors are influenced by
      endogenous modulators such as the neuroactive steroids. Sensitization to these
      compounds influences ethanol dependence and withdrawal and may explain gender
      differences in the molecular effects of ethanol. Furthermore, GABA(A) receptors
      may also play a role in ethanol self-administration via the mesolimbic reward
      system. Ethanol tolerance and dependence may be explained, in part, by changes in
      the function of GABA(A) receptors. We have proposed that alterations in native
      GABA(A) receptor subunit assembly could alter the functional properties of these
      receptors. However, post-translational modifications or other post-synaptic
      mechanisms may also explain changes in GABA(A) receptor function. Genetic animal
      models of ethanol dependence have also identified GABA(A) receptor genes as
      likely mediators of the behavioral adaptations associated with ethanol dependence
      and withdrawal. A better understanding of the effects of ethanol at GABA(A)
      receptors has highlighted important potential mechanisms involved in the
      development of alcoholism.

PMID- 9768539
TI  - Advances in development of medications for alcoholism treatment.
AB  - Over the past decade, research on medications to treat alcohol problem has
      flourished. Naltrexone and acamprosate are tangible fruits of such endeavors and
      each has now earned approval in a large number of countries. Recent studies on
      naltrexone indicate that patient compliance is important if full benefits are to
      be achieved. Several laboratory studies with human subjects are beginning to
      elucidate the mechanisms underlying efficacy of naltrexone, as well as explaining
      variability of response among subpopulations of drinkers. In addition to these
      two agents, recent investigations have also demonstrated that the antidepressants
      desipramine, imipramine, and fluoxetine reduce mood-related symptoms and, to some
      extent, drinking itself in alcoholics who are depressed. Research to date
      suggests that opioid antagonists and selective serotonin reuptake inhibitors are
      more effective in reducing alcohol intake when used in combination. Clinical
      issues, methodology, and directions for future research are also reviewed in this
      article. In particular, issues addressed include alternative dosage regimens,
      necessary duration of treatment, employment of medications in combination,
      integration of pharmacologic agents with behavioral interventions, enhancement of
      patient compliance, and concurrent treatment of psychiatric comorbidity.

PMID- 9768540
TI  - Role of hippocampus in alcohol-induced memory impairment: implications from
      behavioral and immediate early gene studies.
AB  - Acute alcohol intoxication disrupts memory acquisition in humans and laboratory
      animals. This review summarizes recent behavioral and immediate early gene
      expression studies addressing the mechanisms of this phenomenon. Most behavioral
      investigations agree that the amnestic effect of alcohol is due to its
      preferential detrimental effect on hippocampus-dependent than on hippocampus
      independent forms of learning. However, some hippocampal lesion studies
      contradict these results. Learning in behavioral paradigms is accompanied by
      induction of c-fos and other immediate early genes in many brain regions of the
      animal. In contrast, studies on alcohol-mediated changes in expression of this
      gene confirm selective hippocampal suppression of basal and experience-induced
      expression of c-fos after acute and repeated administration of alcohol. This
      hippocampal suppression is in marked contrast with alcohol-mediated induction of
      c-fos expression in other brain areas. However, the selective suppression of
      hippocampal gene expression and memory by alcohol is most likely mediated by a
      number of interacting neurotransmitter systems. Thus, effects of lower doses of
      alcohol (0.5 g/kg or lower in rats) seem to be preferentially mediated through
      GABAergic systems. At intermediate doses (0.75-2 g/kg), several other
      neurotransmitter systems are affected besides GABA. Higher doses lead to none
      specific effects, probably involving even more neurotransmitter systems.
      Elucidation of these neurotransmitter systems will be highly important for
      developing rational approaches for correction of alcohol-related cognitive
      disorders.

PMID- 9768541
TI  - Naltrexone treatment of comorbid alcohol and cocaine use disorders.
AB  - Naltrexone (NTX) has been shown to be efficacious for the treatment of alcohol
      dependence. Since alcohol and cocaine use disorders commonly co-occur, we
      conducted a randomized, double-blind, placebo-controlled trial of NTX 50 mg/day
      in 64 subjects with comorbid alcohol and cocaine use disorders. Although subjects
      in both groups reduced their consumption of both alcohol and cocaine during the 8
      week trial, there was no consistent advantage to NTX over placebo treatment. We
      conclude that, due to behavioral, neurochemical, or other factors, individuals
      with both alcohol and cocaine use disorders are distinct from those dependent on
      alcohol alone, and that NTX at a dosage of 50 mg/day is not efficacious in this
      patient population. Several factors, including medication dosage, length of
      treatment, sample size and attrition rate, limit the interpretation of these
      findings. Consequently, we recommend that subsequent trials of NTX to reduce the
      risk of relapse in patients with comorbid alcohol and cocaine use disorders take
      these issues into account.

PMID- 9768542
TI  - Naltrexone reduces ethanol- and sucrose-reinforced responding in rhesus monkeys.
AB  - These experiments evaluated the ability of naltrexone (NTX) to reduce selectively
      oral and i.v. ethanol-reinforced responding, and examined the ethanol-NTX
      interaction in terms of the competitive opioid antagonist property of NTX. Five
      rhesus monkeys self-administered ethanol or sucrose and concurrently available
      water. Ethanol concentration was varied from 0.25% to 8% (w/v). Naltrexone (0.032
      0.32 mg/kg) or saline was given i.m. 30 min prior to some drinking sessions. NTX
      (0.32 mg/kg) reduced ethanol-reinforced responding at the concentration that
      maintained the most responding (1% or 2%). NTX (0.1 mg/kg) reduced ethanol
      reinforced responding, both at a low ethanol concentration (0.25%) that produced
      little ethanol intake (g/kg), and at a higher concentration (4%) with an
      appreciable intake. Thus, NTX (0.1 mg/kg) shifted the ethanol concentration
      consumption curve down, in an insurmountable manner. NTX (0.1 and 0.32 mg/kg)
      also reduced reinforced responding for sucrose 100 g/l. In another experiment,
      three rhesus monkeys were given opportunities to self-administer ethanol i.v. NTX
      (0.1 mg/kg) reduced the number of ethanol injections obtained by the monkeys at
      all ethanol doses tested (0.01, 0.032, and 0.1 g/kg per injection). The dose
      effect curve was also shifted down. These results showed that NTX reduced
      behavior maintained by either ethanol or sucrose non-selectively. Furthermore,
      the ability of NTX to suppress ethanol-reinforced responding did not depend on
      the route of ethanol administration and was not overcome by increasing the
      concentration or dose per injection of ethanol.

PMID- 9768543
TI  - Extinction of ethanol-induced conditioned place preference and conditioned place
      aversion: effects of naloxone.
AB  - Four experiments examined the effect of naloxone pretreatment on the expression
      and extinction of ethanol-induced conditioned place preference (experiments 1, 2,
      4) or conditioned place aversion (experiments 1, 3). DBA/2 J mice received four
      pairings of a distinctive tactile (floor) stimulus (CS) with injection of ethanol
      (2 g/kg) given either immediately before or after 5-min exposure to the CS. A
      different stimulus was paired with injection of saline. Pre-CS injection of
      ethanol produced conditioned place preference, whereas post-CS injection of
      ethanol produced conditioned place aversion. Both behaviors extinguished
      partially during repeated choice testing after vehicle injection. Naloxone (10
      mg/kg) had little effect on the initial expression of conditioned place
      preference, but facilitated its extinction. Moreover, repeated naloxone testing
      resulted in the expression of a weak conditioned place aversion to the CS that
      initially elicited a place preference. In contrast, naloxone (1.5 or 10 mg/kg)
      enhanced expression of conditioned place aversion, thereby increasing its
      resistance to extinction. A control experiment (experiment 4) indicated that
      repeated testing with a different aversive drug, lithium chloride, did not affect
      rate of extinction or produce an aversion to the CS previously paired with
      ethanol. These findings do not support the suggestion that naloxone facilitates
      the general processes that underlie extinction of associative learning. Also,
      these data are not readily explained by the conditioning of place aversion at the
      time of testing. Rather, naloxone's effects appear to reflect a selective
      influence on maintenance of ethanol's conditioned rewarding effect, an effect
      that may be mediated by release of endogenous opioids. Overall, these findings
      encourage further consideration of the use of opiate antagonists in the treatment
      of alcoholism.

PMID- 9768544
TI  - Changes in the amygdala amino acid microdialysate after conditioning with a cue
      associated with ethanol.
AB  - Excitatory amino acid neurotransmission within the amygdala has been implicated
      in learning associations between external stimuli and intrinsic reward values,
      such that it may play a key role in conditioned drug effects. In the present
      studies, the responses of the excitatory amino acids, aspartate and glutamate,
      together with the neuromodulatory sulphonated amino acid, taurine, within the
      basolateral amygdala, to an odor cue repeatedly associated with acute ethanol
      injections (2 g/kg, i.p.) have been investigated by a microdialysis technique
      combined with HPLC-EC analysis. After presentation of the ethanol-conditioned
      stimulus, a single i.p. saline injection induced an immediate and significant
      increase in the taurine microdialysate content which could be related to the
      neuromodulatory action of taurine. Furthermore, when the conditioned stimulus was
      combined with the ethanol injection (2 g/kg, i.p.), significant increases in both
      taurine and glutamate microdialysate content were observed and indicated a
      learned compensatory response to counteract the acute effects of ethanol. These
      results demonstrate that changes in amygdala extracellular glutamate and taurine
      concentrations can be conditioned to ethanol-associated stimuli and are therefore
      probably implicated in the phenomenon of environmental-dependent tolerance to
      ethanol.

PMID- 9768545
TI  - Ethanol and negative feedback regulation of mesolimbic dopamine release in rats.
AB  - The objectives of this study were to examine the relationship between
      somatodendritic and terminal field dopamine (DA) release following manipulation
      of DA D2 receptors in the ventral tegmental area (VTA), systemic administration
      of ethanol, and inhibition of DA uptake in the nucleus accumbens (ACB). Perfusion
      of 5, 25 and 100 microM quinpirole (a D2 agonist), or sulpiride (a D2 antagonist)
      through the microdialysis probe in the VTA produced dose-related decreases or
      increases, respectively, in the extracellular levels of DA in both the VTA and
      ACB of adult Wistar rats. The IP administration of 2-3 g/kg ethanol produced a
      sustained increase in the extracellular levels of DA (150-200% of baseline) in
      the ACB for at least 2 h after injection, whereas only a transient increase was
      observed in the VTA. Local perfusion of the ACB with 100 microM GBR12909, a DA
      uptake inhibitor, elevated the extracellular levels of DA in the ACB to
      approximately 400% of baseline, but decreased the extracellular levels of DA in
      the VTA to approximately 50% of baseline. Overall, the results suggest that (a)
      there is an association between somatodendritic and terminal field DA release
      when D2 cell body autoreceptors in the VTA are manipulated, (b) elevating
      synaptic levels of DA in the terminal field activates a long-loop negative
      feedback system to the VTA, and (c) different mechanisms may be mediating the
      actions of ethanol on DA neuronal activity and terminal DA release.

PMID- 9768546
TI  - Pharmacological analysis of the heterogeneous discriminative stimulus effects of
      ethanol in rats using a three-choice ethanol-dizocilpine-water discrimination.
AB  - The present study used a three-choice operant drug discrimination procedure to
      determine if NMDA-mediated discriminative stimulus effects could be separated
      from other stimulus effects of 2.0 g/kg ethanol. Adult male Long-Evans rats (n =
      7) were trained to discriminate dizocilpine (0.17 mg/kg; i.g.) from ethanol (2.0
      g/kg; i.g.) from water (4.7 ml; i.g.) using food reinforcement. Substitution
      tests were conducted following administration of the GABA(A) positive modulators
      allopregnanolone (5.6-30.0 mg/kg; i.p.), diazepam (0.3-10.0 mg/kg; i.p.) and
      pentobarbital (1.0-21.0 mg/kg; i.p.), the non-competitive NMDA antagonist
      phencyclidine (0.3-10.0 mg/kg; i.p.), the 5-HT1 agonists TFMPP (0.3-5.6 mg/kg;
      i.p.) and RU 24969 (0.3-3.0 mg/kg; i.p.), and isopropanol (0.10-1.25 g/kg; i.p.).
      Allopregnanolone, diazepam and pentobarbital substituted completely (>80%) for
      ethanol. Isopropanol partially (77%) substituted for ethanol. Phencyclidine
      substituted completely for dizocilpine. RU 24969 and TFMPP did not completely
      substitute for either training drug, although RU 24969 partially (62%)
      substituted for ethanol. Successful training of this three-choice discrimination
      indicates that the discriminative stimulus effects of 0.17 mg/kg dizocilpine were
      separable from those of 2.0 g/kg ethanol. The finding that attenuation of NMDA
      mediated effects of ethanol occurred without altering significantly GABA(A)- and
      5-HT1-mediated effects suggests that the NMDA component may be independent of
      other discriminative stimulus effects of 2.0 g/kg ethanol.

PMID- 9768547
TI  - The discriminative stimulus effects of ethanol are mediated by NMDA and GABA(A)
      receptors in specific limbic brain regions.
AB  - This study was conducted to assess the involvement of N-methyl-D-aspartate (NMDA)
      and gamma-aminobutyric acid (GABA) receptor systems, located in specific limbic
      brain regions. in the discriminative stimulus effects of ethanol. Male Long-Evans
      rats were trained to discriminate between intraperitoneal (i.p.) injections of
      ethanol (1 g/kg) and saline on a two-lever drug discrimination task. The rats
      were then implanted with bilateral injector guides aimed at the nucleus accumbens
      core (AcbC), prelimbic cortex (PrLC), hippocampus area CA1 (CA1), or extended
      amygdala (i.e., at the border of the central and basolateral nuclei). Infusions
      of the non-competitive NMDA antagonist MK 801 in the AcbC or CA1 resulted in dose
      dependent full substitution for i.p. ethanol. MK 801 infusion in the PrLC or
      amygdala failed to substitute for ethanol. Injection of the competitive NMDA
      antagonist CPP in the AcbC also failed to substitute for ethanol. Co-infusion of
      MK 801 in the hippocampus potentiated the effects of MK 801 in the AcbC, whereas
      NMDA infusion in the hippocampus attenuated the ability of MK 801 in the AcbC to
      substitute for ethanol. The direct GABA(A) agonist muscimol resulted in dose
      dependent full substitution for i.p. ethanol when it was injected into the AcbC
      or amygdala, but failed to substitute when administered in the PrLC. Co-infusion
      of MK 801, but not CPP, potentiated the effects of muscimol in the AcbC. These
      results demonstrate that ethanol's discriminative stimulus function is mediated
      centrally by NMDA and GABA(A) receptors located in specific limbic brain regions.
      The data also suggest that the discriminative stimulus effects of ethanol are
      mediated by interactions between ionotropic GABA(A) and NMDA receptors in the
      nucleus accumbens, and by interactions among brain regions.

PMID- 9768548
TI  - Blocking GABA(A) receptors in the anterior ventral tegmental area attenuates
      ethanol intake of the alcohol-preferring P rat.
AB  - The effect of blocking the A subtype of gamma-aminobutyric acid (GABA(A))
      receptors in the anterior ventral tegmental area (VTA) on ethanol (EtOH; 10% v/v)
      and saccharin (SACC; 0.0125%) consumption was investigated in alcohol-preferring
      P rats. Picrotoxin (0.005, 0.01, 0.05 and 0.10 microg/0.5 microl) was injected
      into the VTA, and consumption of EtOH and SACC was assessed in two 2-h limited
      access drinking paradigms (concurrent EtOH/SACC access, and alternate-day-access
      to EtOH and SACC). Under concurrent-access conditions, the picrotoxin
      microinjections resulted in a 55 and 84% decrease in EtOH consumption at the 0.05
      and 0.10 microg doses, respectively, compared with consumption following
      microinjections of vehicle solution (P<0.05). Saccharin intake was not
      significantly altered by picrotoxin. Under alternate-day-access drinking
      conditions, the picrotoxin microinjections resulted in dose-dependent decreases
      in EtOH consumption of 37-68%, with significant decreases following the 0.005,
      0.05 and 0.10 microg doses (P<0.04). Saccharin intake was significantly reduced
      only at the 0.05 microg dose. The decrease in EtOH consumption after 0.10 microg
      picrotoxin was attenuated by co-administration of 0.01 microg muscimol. This dose
      of muscimol had no effect on EtOH consumption when injected alone. Intra-VTA
      injections of bicuculline (0.04 microg), another GABA(A) antagonist, reduced EtOH
      intake, comparable to the reduction following 0.10 microg picrotoxin.
      Microinjections of 0.10 microg picrotoxin in regions outside the VTA failed to
      decrease EtOH intake. These results suggest that anterior VTA mechanisms
      regulating alcohol drinking behavior are under tonic GABA inhibition, mediated by
      GABA(A) receptors. The results also suggest that different neural mechanisms are
      regulating voluntary EtOH and SACC drinking behaviors.

PMID- 9768549
TI  - Dissociation of consummatory and vocal components of feeding in squirrel monkeys
      treated with benzodiazepines and alcohol.
AB  - The primary aim of the current experiments was to develop methods that engender
      vocalizations associated with positive social situations comprising affiliative
      behavior and feeding that could be quantified under controlled laboratory
      conditions and were sensitive to anxiolytic drugs. Classical conditioning
      procedures were used to elicit vocalizations during presentation of stimulus
      lights (i.e., CS condition) previously paired with either preferred foods (e.g.,
      grapes, peanuts, bananas) or standard foods (e.g., monkey chow) as well as during
      presentation of both food types (i.e., UCS condition). When compared to the
      period before stimulus light presentation (i.e., Pre-CS condition), the rate,
      duration and number of elemental units of food-related "twitter" vocalizations
      were increased during the CS conditions regardless of food type. Monkeys spent
      significantly more time oriented toward the food box during the light stimulus
      that preceded preferred food than for the light stimulus that preceded standard
      food. However, twitter vocalizations were higher for standard food regardless of
      the stimulus conditions (i.e., Pre-CS, CS and UCS). Administration of the
      benzodiazepine full agonist chlordiazepoxide (CDP, 1-10 mg/kg), the partial
      agonist bretazenil (BRZ, 1-10 mg/kg), the antagonist flumazenil (FLZ, 1-10 mg/kg)
      and ethyl alcohol (EtOH, 0.1-1.0 g/kg) differentially altered vocalizations.
      Although CDP and BRZ increased feeding of standard food, twitters were reduced
      across stimulus conditions. CDP and BRZ did not alter other social contact calls
      (i.e., "peeps"). FLZ also reduced twitters without altering peeps, but did not
      increase feeding. In contrast, EtOH did not increase feeding or peeps, but did
      increase food-related twitters. These results indicate that there is a
      dissociation between food-related behaviors, such as food consumption and
      orientation towards the food source, and vocal behaviors associated with group
      communication during feeding.

PMID- 9768550
TI  - Effects of third intracerebroventricular injections of corticotropin-releasing
      factor (CRF) on ethanol drinking and food intake.
AB  - Corticotropin releasing factor (CRF), a neuropeptide secreted by hypothalamic and
      extrahypothalamic neurons, is thought to mediate stress-related behaviors. The
      tension reduction hypothesis suggests that ethanol drinking reduces stress; that
      drinking is reinforced by this reduced stress; and that the probability of
      drinking therefore subsequently increases. CRF also decrease food intake, and
      might decrease ethanol drinking similarly. We addressed these hypotheses directly
      by assessing the effects of intracerebroventricular (i.c.v.) CRF upon ethanol
      drinking (1 h/day). Rats were provided drinking tubes containing ethanol
      solutions that were gradually incremented in concentration (from 2% to 8% w/v,
      over 38 days). Ethanol intakes remained stable, ranging from 0.4 to 0.5 g/kg per
      hour on average, and a two-bottle choice test revealed that ethanol was preferred
      reliably to water. Third-i.c.v. cannulae were surgically implanted and CRF or
      vehicle was acutely injected immediately prior to the sessions. CRF dose
      dependently reduced ethanol intake by 31% (0.5 microg) and 64% (5.0 microg), and
      reduced 24-h food by 9% and 21%, respectively, but did not alter body weights.
      I.c.v. CRF reduced ethanol drinking despite any acute stress-like effects that
      may have been present. Hence, these data are inconsistent with the tension
      reduction hypothesis. On the other hand, our results support the concept that
      food intake and ethanol drinking may be mediated by similar mechanisms.

PMID- 9768551
TI  - Are some of the effects of ethanol mediated through NPY?
AB  - Central administration of neuropeptide Y (NPY) in low concentrations has been
      shown to produce anxiolysis and suppression of locomotor activity, a behavioral
      profile not dissimilar to that of ethanol. The present study was conducted to
      ascertain whether NPY and ethanol have similar electrophysiological profiles and
      to evaluate the combined actions of NPY and ethanol. Eighty-five Wistar rats were
      stereotaxically implanted with electrodes aimed at dorsal hippocampus, amygdala,
      and frontal cortex. Rats were administered NPY [or saline (SAL)]
      intracerebroventricularly (i.c.v.) whereas the doses of alcohol (or SAL) were
      given intraperitoneally (i.p.). Two doses of alcohol (0.75, 1.5 g/kg) and two
      doses of NPY (1, 3 nmol) were given alone and in combination. Drug effects were
      assessed using event related potentials (ERP) recorded in response to an auditory
      "oddball" plus noise paradigm between 30 and 40 min post-drug. Multivariate
      analyses of variance (MANOVA) revealed that NPY produced a significant decrease
      in the amplitude and increase in the latency of the N1 component in cortex and a
      decrease in the amplitude of the P3 component in amygdala, but no overall effects
      in hippocampus. Ethanol produced identical effects to NPY on the N1 and P3
      components of the ERP in cortex and amygdala. Combined administration of EtOH and
      NPY (1 nmol) produced effects equivalent to those seen following the higher doses
      of NPY (3 nmol) or EtOH (1.5 g/kg). These studies demonstrate that NPY and
      ethanol have a similar electrophysiological profile. In addition, the combined
      administration of NPY and ethanol produced additive effects.

PMID- 9768552
TI  - Repeated ethanol withdrawal experience selectively alters sensitivity to
      different chemoconvulsant drugs in mice.
AB  - Repeated ethanol withdrawal experience has been shown to result in exacerbated
      seizures associated with future withdrawal episodes. This sensitization of the
      withdrawal response has been postulated to represent a "kindling" phenomenon. The
      present study employed an established model of repeated ethanol withdrawals to
      examine the potential role of GABA(A), and NMDA and non-NMDA glutamate receptor
      systems in mediating enhanced seizure activity, as assessed by sensitivity to
      seizures induced by pentylenetetrazol (PTZ), NMDA, and kainic acid (KA) i.v.
      infusions, respectively. Adult C3H mice were chronically exposed to ethanol vapor
      in inhalation chambers. A multiple withdrawal (MW) group received four cycles of
      16-h ethanol vapor exposure interrupted by 8-h periods of abstinence; a single
      withdrawal (SW) group was tested after a single 16-h bout of ethanol
      intoxication; and the third group was ethanol-naive, serving as controls (C).
      Results indicated that the MW group evidenced significantly lower PTZ and NMDA
      seizure thresholds compared to SW and C groups at 8 and 24 h post-withdrawal. In
      contrast, MW and SW groups exhibited reduced sensitivity (higher seizure
      threshold) to KA in comparison to controls, and this effect only emerged at 24 h
      post-withdrawal. Further, MW mice required significantly less additional PTZ or
      NMDA to induce more severe convulsions once initial signs of seizures were
      elicited. Conversely, latency and amount of KA required to transition from
      initial seizure signs to more severe end-stage convulsions was significantly
      greater for MW and SW groups compared to controls. Taken together, these results
      suggest that repeated ethanol withdrawal experience does not result in a global
      non-specific lowering of threshold to convulsive stimuli, but rather, selective
      changes in CNS mechanisms associated with neural excitability may underlie
      potentiated withdrawal responses. Thus, reduced GABA(A) receptor function and
      increased NMDA receptor activity may become exaggerated as a consequence of
      repeated withdrawal experience, while reduced sensitivity to KA induced seizures
      may represent a compensatory response to withdrawal-related CNS
      hyperexcitability.

PMID- 9768553
TI  - Effects of ethanol on Pavlovian autoshaping in rats.
AB  - Approach responses, consummatory behaviors, and directed motor responses
      maintained by food reward resemble autoshaping CRs and are increased by lower
      doses of ethanol. This study evaluated the effects of presession i.p. injections
      of ethanol doses (0.00, 0.25, 0.50, 0.70. or 1.00 g/kg) on the acquisition of
      lever-press autoshaping CR performance in groups of male Long-Evans hooded rats.
      Paired groups received 15 daily sessions of Pavlovian autoshaping procedures,
      wherein the insertion of a retractable lever for 5 s (CS) was followed by the
      response-independent presentation of food (US). Ethanol facilitated lever-press
      autoshaping CR acquisition, as revealed by dose-related increases in the number
      of trials on which CRs were performed. The form of the dose-effect curve was
      inverted U-shaped with maximal responding induced during sessions 1-5 by the 0.70
      g/kg ethanol dose. A similar dose-effect curve was observed during sessions 11
      15, revealing that the effects of ethanol on autoshaping CR performance were
      relatively stable. A pseudoconditioning control group injected presession with
      0.50 g/kg ethanol received training wherein the food US was presented randomly
      with respect to the lever CS. Few lever-presses were performed by the Random 0.50
      group, indicating that ethanol's effects on autoshaping CR acquisition and
      maintenance observed in the Paired 0.50 group were not due to its psychomotor
      activating effects. A non-injection control group performed more autoshaping CRs
      than did the control group injected presession with saline, indicating that daily
      presession i.p. injections per se suppress autoshaping CR performance. Results
      reveal that low doses of ethanol enhance Pavlovian conditioning of directed motor
      and consummatory-like responding maintained by food reward. Implications for
      autoshaping accounts of impulsivity and drug abuse are considered.

PMID- 9768554
TI  - Alcohol-heightened aggression in mice: attenuation by 5-HT1A receptor agonists.
AB  - One of the critical mechanisms by which alcohol heightens aggression involves
      forebrain serotonin (5-HT) systems, possibly via actions on 5-HT1A receptors. The
      present experiments tested the hypothesis that activating 5-HT1A receptors by
      selective agonists will block the aggression-heightening effects of ethanol.
      Initially, the selective antagonist WAY 100635 was used to assess whether or not
      the changes in aggressive behavior after treatment with 8-OH-DPAT and flesinoxan
      result from action at the 5-HT1A receptors. Resident male CFW mice engaged in
      aggressive behavior (i.e. attack bites, sideways threats, tail rattle) during 5
      min confrontations with a group-housed intruder male. Quantitative analysis of
      the behavioral repertoire revealed systematic reductions in all salient elements
      of aggressive behavior after treatment with 8-OH-DPAT (0.1-0.3 mg/kg, i.p.) or
      flesinoxan (0.1-1.0 mg/kg, i.p.). The 5-HT1A agonists also reduced motor
      activities such as walking, rearing and grooming, although to a lesser degree.
      Pretreatment with the antagonist WAY 100635 (0.1 mg/kg, i.p.) shifted the agonist
      dose-effect curves for behavioral effects to the right. In a further experiment,
      oral ethanol (1.0 g/kg, p.o.) increased the frequency of attacks in excess of 2
      SD from their mean vehicle level of attacks in 19 out of 76 resident mice. Low
      doses of 8-OH-DPAT (0.03-0.3 mg/kg) and flesinoxan (0.1, 0.3, 0.6 mg/kg), given
      before the ethanol treatment, attenuated the alcohol-heightened aggression in a
      dose-dependent fashion. By contrast, these low 5-HT1A agonist doses affected
      motor activity in ethanol-treated resident mice to a lesser degree, suggesting
      behavioral specificity of these anti-aggressive effects. The current results
      support the hypothesized significant role of 5-HT1A receptors in the aggression
      heightening effects of alcohol. If these effects are in fact due to action at
      somatodendritic 5-HT1A autoreceptors, then the anti-aggressive effects would be
      associated with decreased 5-HT neurotransmission.

PMID- 9768555
TI  - Relationship between anticonvulsant activity and plasma level of some 2,3
      benzodiazepines in genetically epilepsy-prone rats.
AB  - The anticonvulsant effects of some novel 2,3-benzodiazepines acting as alpha
      amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid/kainate (AMPA/KA) antagonists
      were evaluated in genetically epilepsy prone rats. The ED50 values against clonic
      and tonic seizures (in micromol/kg) revealed that the rank order of
      anticonvulsant activity was: GYKI 52466 > 2,3BZ-2 > 2,3 MBZ-2 > NBQX. Maximal
      anticonvulsant protection was observed 15-45 min after the i.p. administration of
      NBQX and GYKI 52466, 30-90 min after the i.p. administration of 2,3BZ-2, and 45
      120 min after the i.p. administration of 2,3MBZ-2. The time course of plasma
      levels of rats treated with GYKI 52466 showed that peak plasma concentration was
      observed 15 min after i.p. administration, 2,3BZ-2 revealed that peak plasma
      concentration was achieved 45 min after i.p. administration, whereas following
      2,3MBZ-2 administered i.p., two curves were detected; one is referred to the
      parent compound and the other to its demethylate metabolite that corresponds to
      2,3BZ-2. The therapeutic index (ratio of TD50 values for impaired rotarod
      performance and ED50 values for anticonvulsant activity) revealed that NBQX and
      GYKI 52466 were slighly more toxic than 2,3BZ-2 and 2,3MBZ-2. The present data
      suggest that 2,3-benzodiazepines acting at AMPA/kainate receptors play an
      important role in the generation and/or propagation of the audiogenic seizures in
      genetically epilepsy-prone rats.

PMID- 9768556
TI  - Effects of LHRH on avoidance conditioning in normally cycling and ovariectomized
      female rats.
AB  - Several studies have demonstrated that the peptide LHRH can modify behavior in
      the male rat. Peripheral and intracerebral infusions of LHRH impair the
      acquisition of conditioned avoidance responses (CARs) and increase some
      spontaneous motor behaviors, such as head shaking and grooming. The present study
      was undertaken to detect the effects of LHRH on the acquisition of CARs and
      spontaneous motility in normally cycling and ovariectomized (OVX) Sprague-Dawley
      female rats. Normally cycling females were separated in four groups, according to
      the stage of the estrous cycle. Ovariectomized female rats were pretreated, 48 h
      before the experiment, with estradiol benzoate (10 microg/kg) or corn oil. LHRH
      (6.25, 25, or 50 microg/kg) was subcutaneously injected and the behavioral tests
      began 1 h after. Low doses of LHRH stimulated the acquisition of CARs during
      proestrus, estrus, and metestrus, whereas higher doses impaired conditioning in
      all the four stages of the cycle. High doses of LHRH impaired acquisition in OVX
      rats treated with oil and potentiated the depressant effects of EB on this
      behavior. The effects of LHRH on spontaneous motor activity were either
      stimulatory or inhibitory, according to the hormonal status and the dose
      administered. High doses of LHRH decreased motor responses in the diestrous rat.
      All the doses of LHRH increased the number of headshakes during proestrus,
      estrus, and metestrus, while the other motor responses were scarcely or not
      affected by LHRH in these stages. In OVX rats LHRH increased rearing, head
      shaking, and grooming behavior. These results support a role of LHRH in the
      modulation of conditioned and spontaneous behavior. They could provide an
      explanation to the behavioral changes observed across the estrous cycle and those
      observed after EB priming in OVX rats.

PMID- 9768557
TI  - Maternal exposure to low doses of delta9-tetrahydrocannabinol facilitates
      morphine-induced place conditioning in adult male offspring.
AB  - The possible existence of an increased susceptibility to the reinforcing
      properties of morphine was analyzed in male and female rats born from mothers
      exposed to delta9-tetrahydrocannabinol (THC, 1, 5, or 20 mg/kg) during gestation
      and lactation. Maternal exposure to low doses of THC (1 and 5 mg/kg), relevant
      for human consumption, resulted in an increased response to the reinforcing
      effects of a moderate dose of morphine (350 microg/kg), as measured in the place
      preference conditioning paradigm (CPP) in the adult male offspring. These animals
      also displayed an enhanced exploratory behavior in the defensive withdrawal test.
      However, only females born from mothers exposed to THC 1 mg/kg exhibited a small
      increment in the place conditioning induced by morphine. The possible implication
      of the hypothalamo-pituitary-adrenal axis (HPA) was analyzed by monitoring plasma
      levels of adrenocorticotropic hormone (ACTH) and corticosterone in basal and
      moderate-stress conditions (after the end of the CPP test). Female offspring
      perinatally exposed to THC (1 or 5 mg/kg) displayed high basal levels of
      corticosterone and a blunted adrenal response to the HPA-activating effects of
      the CPP test. However, male offspring born from mothers exposed to THC (1 or 5
      mg/kg) displayed the opposite pattern: normal to low basal levels of
      corticosterone, and a sharp adrenal response to the CPP challenge. The present
      study reveals that maternal exposure to low doses of THC results in an increased
      sensitivity to the reinforcing effects of morphine in the adult male offspring,
      and in sexually dimorphic behavioral and endocrine alterations in the adaptative
      responses to stressors such as novelty or place-preference testing. These results
      support the growing evidence of the importance of monitoring the long-term
      consequences of maternal consumption of cannabis derivatives.

PMID- 9768558
TI  - Pharmacological characterization of 6-bromo-3'-nitroflavone, a synthetic
      flavonoid with high affinity for the benzodiazepine receptors.
AB  - 6-Bromo-3'-nitroflavone is a synthetic flavone derivative that selectively
      recognizes benzodiazepine receptors and has potent anxiolytic-like effects. Here,
      we describe in detail its pharmacological characterization. When i.p. injected in
      mice, 6-bromo-3'-nitroflavone (0.01-0.3 mg/kg) had an anxiolytic-like effect in
      the elevated plus-maze test. This effect was blocked by the specific
      benzodiazepine receptor antagonist, flumazenil. In addition, it exhibited
      anxiolytic-like actions when given orally (1 mg/kg). 6-Bromo-3'-nitroflavone did
      not exhibit myorelaxant effects (up to 30 mg/kg, i.p.). Unlike diazepam, this
      flavonoid produced no anterograde amnesia in a one-trial inhibitory avoidance
      learning. On the other hand, 6-bromo-3'-nitroflavone possessed mild
      anticonvulsant activity (0.1 mg/kg, i.p.) and provoked sedative-depressant
      actions only at doses 100-1000 times higher than those producing anxiolytic-like
      effects. 6-Bromo-3'-nitroflavone (0.1-1 mM) produced a lower potentiation of
      gamma-amino-butyric acid (GABA)-stimulated 36Cl- influx (126-138%) in comparison
      to diazepam (0.1 mM: 166%) in cerebral cortical membrane vesicles. Taken
      together, these findings suggest that 6-bromo-3'-nitroflavone has anxiolytic-like
      action possibly behaving as a partial agonist of the benzodiazepine receptors.

PMID- 9768559
TI  - Beneficial effects of acute and repeated administrations of sigma receptor
      agonists on behavioral despair in mice exposed to tail suspension.
AB  - In an attempt to examine whether sigma receptor agonists alleviate behavioral
      despair, we investigated the effects of sigma receptor agonists on the tail
      suspension-induced immobility in mice. The acute and repeated (14 days)
      administrations of sigma1 receptor agonists, such as 1-(3,4-dimethoxyphenethyl)-4
      (3-phenylpropyl)piperazine dihydrochloride (SA4503) (1 and/or 3 mg/kg) and (+)
      pentazocine (5.6 mg/kg), sigma1/2 receptor agonists, such as 1,3-di(2
      tolyl)guanidine (DTG) (3 and/or 5.6 mg/kg), desipramine (7.5 and/or 15 mg/kg),
      and fluoxetine (10 and/or 20 mg/kg), reduced immobility in mice exposed to tail
      suspension. N,N-Dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl] ethylamine
      monohydrochloride (NE-100), a sigma1 receptor antagonist, significantly
      antagonized the decrease in immobility induced by acute administrations of SA4503
      (1 mg/kg) and (+)-pentazocine (5.6 mg/kg). Although not significant, NE-100
      showed a tendency to inhibit the DTG (5.6 mg/kg)-induced decrease in immobility.
      In contrast, repeated administrations of SA4503 (1 and 3 mg/kg), (+)-pentazocine
      (5.6 mg/kg) or DTG (5.6 mg/kg) failed to affect the increase in body weight.
      These results suggest that acute and repeated stimulations of sigma, possibly a
      sigma1 receptor subtype, alleviate behavioral despair, unaccompanied with changes
      in body weight.

PMID- 9768560
TI  - Behavioral pharmacology of zolpidem relative to benzodiazepines: a review.
AB  - Zolpidem, an imidazopyridine that purportedly binds selectively to certain
      GABA(A) receptor subtypes, is the most commonly prescribed hypnotic. The present
      article critically reviewed the extant experimental literature to determine
      whether the behavioral pharmacologic profile of zolpidem also differs from that
      of benzodiazepines. Specific topics that are reviewed include: 1) reinforcing
      effects and abuse potential, 2) discriminative-stimulus effects, 3) subject-rated
      drug effects, 4) performance-impairing effects, 5) tolerance-producing effects,
      and 6) physiological dependence-producing effects. Studies that employed both
      nonhumans and humans are reviewed. Based on the available literature, the most
      parsimonious conclusion is that despite its unique neuropharmacological profile,
      the behavioral effects of zolpidem are generally similar to those of
      benzodiazepines. However, it is important to note the dearth of perspective,
      experimental studies that directly compared zolpidem and a benzodiazepine.
      Because of the clinical relevance and paucity of published studies, future
      research should focus explicitly on assessing the reinforcing effects, abuse
      potential, performance-impairing effects, tolerance-producing effects, and
      dependence-producing effects of zolpidem relative to a benzodiazepine. Important
      issues such as the selection of an appropriate comparison drug and subject
      population, and the doses tested needed to be considered in these future studies.

PMID- 9768561
TI  - The effects of inhaled isoparaffins on locomotor activity and operant performance
      in mice.
AB  - Very little is known qualitatively or quantitatively about the acute central
      nervous system effects of isoparaffin solvents that are widely used in household
      and commercial applications. Four isoparaffinic hydrocarbon solvent products
      differing in predominant carbon number and volatility (ISOPAR-C, -E -G, -H) were
      tested for their acute effects on locomotor activity and operant performance
      after inhalation exposure in mice. For both measures, concentration-effect curves
      were obtained for 30-min exposures using a within-subject design. The more
      volatile products, ISOPAR-C and -E, were as easily vaporized under our conditions
      as vapors such as toluene and TCE, which have acute effects on human behavior and
      are abused. ISOPAR-G was slowly volatilized and ISOPAR-H could not be completely
      volatilized within our 30-min exposures, suggesting that acute human exposures
      may be less likely and that it may be more difficult to abuse them. ISOPAR-C, -E,
      and -G produced reversible increases in locomotor activity of mice at 4000 and
      6000 ppm while ISOPAR-C and -E produced reversible concentration-dependent
      decreases in rates of schedule-controlled operant behavior in approximately the
      same concentration range as they affected locomotor activity. The fact that only
      locomotor activity increases were observed with these isoparaffins provides
      evidence that they produce a different pattern of effects than those reported for
      abused solvents such as toluene and TCE. Further research will be needed to
      determine if this different pattern of effects on animal behavior between
      isoparaffins and abused solvents is correlated with a different pattern of acute
      intoxication and abuse potential in humans.

PMID- 9768562
TI  - Nicotine administration impairs sensory gating in Long-Evans rats.
AB  - In rats, effects of nicotine administration on sensory gating as indexed by
      prepulse inhibition (PPI) of the acoustic startle reflex (ASR) are unclear. We
      have found that nicotine administration enhances ASR and PPI in Sprague-Dawley
      rats, but other investigators, using Long-Evans rats, have reported no effects or
      enhancement of PPI only. Numerous methodological differences exist among studies
      in addition to subject strain, however, making it unclear whether inconsistent
      behavioral responses are the result of different experimental procedures or
      indicate a true strain difference. To investigate the role of strain in
      nicotine's effects on ASR and PPI, 192 male and female Long-Evans rats were
      administered 12 mg/kg/day nicotine via osmotic minipump for 14 days using
      identical methodologies employed in studies with Sprague-Dawley subjects. Effects
      of grouped vs. individual housing on these responses also were examined. Nicotine
      administration impaired ASR and PPI in Long-Evans subjects. These effects
      occurred in female rats regardless of housing condition, and interacted with
      housing in male rats. Results indicate that sex and housing are important
      variables in nicotine's effects. Results suggest that subject strain may be an
      important variable in nicotine's effects on sensory gating, and that responses of
      Sprague-Dawley vs. Long-Evans rats may represent a true strain difference.

PMID- 9768563
TI  - Cocaine and caffeine: conditioned place preference, locomotor activity, and
      additivity.
AB  - Conditioned place preference (CPP) was employed to clarify the reinforcing and
      locomotor stimulating effects of several doses of cocaine and caffeine (0.32,
      1.0, 3.2, 5.6, and 10.0 mg/kg) and to explore the possibility of additive effects
      between the two drugs. Additionally, the hypothesis that the reinforcing effects
      of psychostimulants are mediated by the same systems that control psychostimulant
      induced locomotor activity was examined by conducting correlational studies
      between drug-induced locomotor activity and time spent in the drug-conditioned
      compartments. Several doses of cocaine (1.0, 3.0, 5.6, 10.0 mg/kg), and caffeine
      (0.32, 1.0, 3.2, 5.6, 10.0) were found to condition place preference and
      stimulate locomotor activity. A combination of low doses (0.32 mg/kg) of each
      drug appeared to be additive. A positive relationship between locomotor activity
      observed during conditioning and time spent in the conditioned compartment during
      testing was found for cocaine but not caffeine or the low-dose combination of
      cocaine and caffeine.

PMID- 9768564
TI  - The synergistic effects of combining cocaine and heroin ("speedball") using a
      progressive-ratio schedule of drug reinforcement.
AB  - The relative reinforcing value of cocaine/heroin combination ("speedball") was
      compared in the rat using a progressive-ratio (PR) reinforcement schedule. The
      initial training for all rats was a combined dose of 18 microg/kg/inj of heroin
      (H) plus 300 microg/kg/inj of cocaine (C). Break points for the training dose and
      individual component doses were determined for half and double the training dose.
      Of the three doses of each treatment, only C yielded the expected monotonic
      increase in break point as a function of dose. Also, break points for C (300 and
      600 microg/kg/inj) was greater than for the combination of C and H (18 H/300 C
      and 36 H/600 C microg/kg/inj), suggesting a greater reward value for C alone. The
      doses for these three drug treatments that produced saline level break points
      were then determined. At these lower doses, significant break points were
      obtained with the H/C combination at which the respective doses of H or C had
      break points identical to those of saline. These lower dose results indicate that
      the combination is clearly synergistic and that the discrepancy with doses at the
      opposite end of the dose response curve suggest that the PR schedule is
      vulnerable to drug-induced motor effects.

PMID- 9768565
TI  - Phase-response curve for ethanol: alterations in circadian rhythms of temperature
      and activity in rats.
AB  - Circadian rhythms of core body temperature and general activity in Sprague-Dawley
      rats were monitored for 21 days using remote radiotelemetry to examine acute and
      sustained effects of 0 (saline) 1.0, and 2.0 g/kg ethanol injections administered
      at four different times of day. Ethanol produced dose-dependent and statistically
      significant hypothermia and hypoactivity when injected at 0100, 0700, 1300, and
      1900 h; however, the magnitude of the hypothermic effect was greatest at the 1900
      h injection time. Cosinor analyses revealed persistent alterations in both
      activity and temperature rhythms, which lasted for at least 48 h postinjection.
      Ethanol significantly shortened the period of activity rhythms when injected in
      either 1.0 or 2.0 g/kg doses at 0700 and 1300 h, and produced similar period
      shortening effects on temperature rhythms at 1300 and 1900 h. The acrophase of
      the activity rhythm was significantly phase delayed by 1.0 g/kg ethanol at 0700
      h, while the acrophase of temperature was significantly phase advanced by 2.0
      g/kg ethanol at 0100 h, but significantly phase delayed by the same dose
      administered at 1300 h. A statistically significant and dose-dependent reduction
      in the amplitude of the body temperature rhythm was observed at the 1900-h
      administration time. There were no differences in the MESOR (Midline Estimating
      Statistic of Rhythm; i.e., rhythm-adjusted mean value) of either temperature or
      activity circadian rhythms as a function of ethanol treatment at any dose.

PMID- 9768566
TI  - Failure of clonidine to stimulate feeding in healthy humans.
AB  - The alpha2-adrenergic system is involved in the regulation of food intake in
      animals but its effects on feeding in humans are unknown. We hypothesized that
      clonidine administration would stimulate food intake in healthy human subjects.
      Ten men and 4 women, all physically and psychiatrically healthy, received
      clonidine 3 microg/kg or placebo, orally, in blinded, balanced, randomized order.
      Consumption of a liquid test meal was measured; also, serum growth hormone levels
      were used as a secondary measure of clonidine effects. Visual analog scale
      ratings of hunger, satiety, and sedation were obtained before, during, and after
      the test meal. A subset of five subjects also received 1.5 microg/kg clonidine,
      in addition to the two trials described above. Test meal consumption was greater
      following placebo than following clonidine. Sedation ratings were substantially
      higher at all time points after clonidine and correlated with meal consumption
      (correlation coefficient r = -0.584; p = 0.028). Hunger and satiety ratings did
      not differ. The 1.5 microg/kg dose did not provide different effects on feeding
      from that seen with placebo. Contrary to our hypothesis, clonidine did not
      stimulate food intake in humans. Sedation associated with clonidine
      administration may have suppressed any effects on feeding.

PMID- 9768567
TI  - Agonist properties of N,N-dimethyltryptamine at serotonin 5-HT2A and 5-HT2C
      receptors.
AB  - Extensive behavioral and biochemical evidence suggests an agonist role at the 5
      HT2A receptor, and perhaps the 5-HT2C receptor, in the mechanism of action of
      hallucinogenic drugs. However the published in vitro pharmacological properties
      of N,N-dimethyltryptamine (DMT), an hallucinogenic tryptamine analog, are not
      consistent with this hypothesis. We, therefore, undertook an extensive
      investigation into the properties of DMT at 5-HT2A and 5-HT2C receptors. In
      fibroblasts transfected with the 5-HT2A receptor or the 5-HT2C receptor, DMT
      activated the major intracellular signaling pathway (phosphoinositide hydrolysis)
      to an extent comparable to that produced by serotonin. Because drug efficacy
      changes with receptor density and cellular microenvironment, we also examined the
      properties of DMT in native preparations using a behavioral and biochemical
      approach. Rats were trained to discriminate an antagonist ketanserin from an
      agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) in a two-lever choice
      paradigm. Pharmacological studies showed that responding on the DOI and
      ketanserin lever reflected agonist and antagonist activity at 5-HT2A receptors,
      and hence, was a suitable model for evaluating the in vivo functional properties
      of DMT. Like other 5-HT2A receptor agonists, DMT substituted fully for DOI.
      Intact choroid plexus was used to evaluate the agonist properties at endogenous 5
      HT2C receptors; DMT was a partial agonist at 5-HT2C receptors in this native
      preparation. Thus, we conclude that DMT behaves as an agonist at both 5-HT2A and
      5-HT2A receptors. One difference was evident in that the 5-HT2C, but not the 5
      HT2A, receptor showed a profound desensitization to DMT over time. This
      difference is interesting in light of the recent report that the hallucinogenic
      activity of DMT does not tolerate in humans and suggests the 5-HT2C receptor
      plays a less prominent role in the action of DMT.

PMID- 9768568
TI  - Naloxone-precipitated morphine withdrawal induced place aversions: effect of
      naloxone at 24 hours postmorphine.
AB  - The aversive properties of naloxone-precipitated withdrawal from acutely
      administered morphine were assessed using the place-conditioning paradigm. The
      conditioned place aversion produced by naloxone (0.5-1.0 mg/kg, s.c.) after two
      conditioning trials was enhanced by pretreatment with morphine (20 mg/kg, s.c.)
      24 h prior to the conditioning trial. Naloxone precipitated withdrawal from
      acutely administered morphine produces an aversive motivational state that
      becomes associated with place cues.

PMID- 9768569
TI  - Nicotine-dizocilpine interactions and working and reference memory performance of
      rats in the radial-arm maze.
AB  - Both nicotinic cholinergic and NMDA glutaminergic systems are important for
      memory function. Nicotine has been found repeatedly to significantly improve
      working memory performance in the radial-arm maze. The NMDA antagonist
      dizocilpine has been found to impair working memory performance. There is
      neuropharmacological evidence that these two systems are functionally related.
      Nicotine is potent at releasing many transmitters including glutamate. The
      current study was conducted to examine the interaction of nicotinic and NMDA
      systems with regard to working and reference memory. Rats were trained on a
      working/reference procedure on a 16-arm radial maze. After acquisition, they were
      administered nicotine (0, 0.2, and 0.4 mg/kg) and dizocilpine (0, 100, and 200
      microg/kg) alone or in combination in a repeated measures, counterbalanced
      design. As seen previously, nicotine at a dose of 0.2 mg/kg caused a significant
      improvement in working but not reference memory performance in the radial-arm
      maze. The 200 microg/kg dose of dizocilpine made the rats nonresponsive on the
      maze so that choice accuracy could not be assessed. The 100 microg/kg dose of
      dizocilpine caused significant impairments in both working and reference memory.
      The 0.4 mg/kg dose of nicotine significantly attenuated the dizocilpine-induced
      deficit in both working and reference memory. NMDA blockade impairs working and
      reference memory and blocks the expression of the working memory improvement
      caused by 0.2 mg/kg of nicotine. However, a higher dose of 0.4 mg/kg of nicotine
      is effective at attenuating the dizocilpine-induced deficit, even though this
      dose alone is not effective in improving performance. A second study examined the
      effects of a lower dose range of dizocilpine. Comensurately smaller memory
      impairments were seen with lower doses of dizocilpine down to 12.5 microg/kg,
      which did not produce any significant effects on memory performance or response
      latency. Nicotine had a more modest effect in attenuating the smaller deficits
      caused by these lower doses of dizocilpine. These studies provide evidence for
      important interactions between nicotinic and NMDA systems with regard to memory
      function.

PMID- 9768570
TI  - Future directions for allergen immunotherapy.
AB  - Over the last 30 years several approaches to modify immunotherapy have been
      tested, including allergoids, alum precipitation, and most recently peptides.
      However, none of these have replaced the traditional regimens. Over the same
      period our scientific understanding of allergic disease has been transformed.
      Today it is possible to identify and monitor changes occurring during treatment
      and to target many different aspects of the immune system. Recombinant technology
      provides a powerful technique both for sequencing proteins and producing
      allergens in commercial quantities. The recombinant proteins can be modified by
      site-directed mutagenesis so as to decrease their reactivity with IgE antibodies
      while maintaining reactivity with T cells. Knowledge of the tertiary structure of
      allergens will make it simpler to identify and change surface epitopes. A
      completely different approach is to use plasmids to introduce the genes for an
      allergen. The strength of this technique is that the plasmid can be designed to
      control expression and also to influence the cytokine profile of the response or
      the isotype of antibodies produced. Finally, different adjuvants can be used with
      proteins to alter the response. These include IL-12, immunostimulatory sequences
      of DNA, and bacterial proteins such as those used in HibVax. It is now possible
      to identify the cells that control the immune response to allergens and to design
      treatments that will either downregulate or change the response of T cells. The
      challenge is to transform this information into an effective treatment for
      allergic disease.

PMID- 9768571
TI  - Biologic activities of IL-1 and its role in human disease.
AB  - The role of the polypeptide proinflammatory cytokine IL-1 family represents a
      group of proteins that have contrasting and synergistic biologic responses. IL
      1alpha and beta and their precursor forms are heavily involved in the enhancement
      of inflammation and host defense. Within this family of gene products, there is
      also a naturally occurring receptor antagonist, IL-1ra, as well as a family of
      receptor proteins that have differential signaling functions and activities. The
      study of these proteins in human disease, including allergic disease and type 1
      hypersensitivity responses, has led to a better understanding of the underlying
      general inflammation associated with these syndromes and has provided
      opportunities to look at new forms of intervention in allergic disease and
      asthma.

PMID- 9768572
TI  - Diagnostic skin testing for natural rubber latex allergy.

PMID- 9768573
TI  - Osteoporosis in the corticosteroid-treated patient with asthma.
AB  - Osteoporosis affects 40% of white women older than 45 years of age and 15% of
      white men older than 50 years of age, resulting in approximately 1.5 million
      annual fractures in the United States. Systemic corticosteroid therapy increases
      the probability of osteoporosis, even with alternate-day dosing and with dosages
      sufficiently low so as not to affect the hypothalamic-pituitary-adrenal axis.
      Inhaled corticosteroid therapy may affect bone density if high-dose therapy is
      given to select individuals. The potential of increasing osteoporosis with
      inhaled corticosteroid asthma therapy is a concern because of the availability of
      more potent inhaled corticosteroid agents and recommendations that inhaled
      corticosteroid therapy be initiated earlier in the course of asthma. This article
      provides suggestions, on the basis of the medical literature and consensus of the
      authors when specific information was not available, for assessing and treating
      osteoporosis in subjects with asthma. Suggested risk categories are "low risk"
      (inhaled corticosteroid dosage of < or =800 microg of heclomethasone dipropionate
      [BDP]/day in adults or < or =400 microg BDP or equivalent in children), "moderate
      risk" (inhaled BDP >800 microg/day in adults or >400 microg/day in children), and
      "high risk" (systemic corticosteroid therapy 4 times a year or daily or alternate
      day systemic corticosteroid therapy). Dosage of nasal corticosteroid probably
      should be added to the orally inhaled corticosteroid for total burden of inhaled
      corticosteroid. Potential treatment strategies based on risk factors and bone
      density if indicated are offered to assist physicians treating patients with
      asthma.

PMID- 9768574
TI  - Comparison of 3 different doses of budesonide and placebo on the early asthmatic
      response to inhaled allergen.
AB  - BACKGROUND: A simple laboratory method to evaluate relative potency of inhaled
      corticosteroids in asthma would be valuable. Single-dose studies with the
      allergen-induced late asthmatic response have failed to show a useful dose
      response relationship. Treatment for several days with inhaled corticosteroids
      will also inhibit the allergen-induced early asthmatic response. METHODS: Twelve
      atopic asthmatic subjects were studied during a season when no medications were
      required except ipratropium bromide as needed. These subjects had positive
      allergen and methacholine inhalation tests and FEV1 greater than 70% of predicted
      value. A double-blind, randomized, cross-over study compared placebo and
      budesonide 100, 200, and 400 microg administered by means of Turbuhaler twice
      daily for 7 days with 6-day washout periods. Methacholine PC20 was measured
      before and after 6 days of treatment, and allergen PC15 was measured after 7 days
      of treatment. RESULTS: The allergen PC15 (n = 11) was significantly larger (P =
      .0001) for all doses of budesonide compared with placebo, but there was no
      significant difference between the 3 doses of budesonide, and no dose response
      was demonstrated. The methacholine PC20 was significantly larger after all
      budesonide treatments compared with placebo (P = .024), but there was no
      difference between the 3 doses. There was a progressive increase in the allergen
      PC15 chronologically (sequence effect) that was not explained by improvement in
      FEV1 or airway responsiveness; sequence effects were not seen for FEV1 or for
      pretreatment or posttreatment methacholine PC20. Statistical adjustment for
      sequence effect did not alter allergen PC15 statistics. CONCLUSION: A 7-day
      course of budesonide administered by means of Turbuhaler at 200, 400, or 800
      microg per day provided marked and significant inhibition of the allergen-induced
      early asthmatic response compared with placebo. There was, however, no difference
      between the 3 doses. Therefore this method with these doses is not useful for
      providing assessment of relative potency.

PMID- 9768575
TI  - Differential regulation of allergen-specific T(H2)- but not T(H1)-type responses
      by alveolar macrophages in atopic asthma.
AB  - BACKGROUND AND OBJECTIVE: Previous studies have suggested that quantitative
      differences in TH2-type cytokine responses in the airways are of particular
      importance in the pathogenesis of asthma. In this study we investigated whether
      alveolar macrophages (AMs) and peripheral blood monocytes (PMNs) are able to
      significantly influence the profiles of allergen-induced TH1 (IFN-gamma) and TH2
      (IL-4 and IL-5) cytokine production by CD4+ T cells in atopic asthmatic subjects
      versus atopic nonasthmatic subjects and nonatopic normal subjects. METHODS:
      Peripheral blood CD4+ T cells were cultured alone or cocultured with either PMNs
      or AMs with allergen stimulation in the 3 groups. RESULTS: Although allergen
      stimulation did not change TH1 or TH2 cytokine responses in cultures of CD4+ T
      cells alone, the addition of PMNs to the cultures induced a significant increase
      in production of IL-4, IL-5, and IFN-gamma (P < .01 or P < .001) in atopic
      asthmatic subjects and atopic nonasthmatic subjects. However, PMNs induced a
      significant increase for IFN-gamma (P < .05) only in normal subjects. AMs from
      atopic asthmatic subjects significantly enhanced production of all 3 cytokines (P
      < .01 or P < .001), whereas the AMs from atopic nonasthmatic subjects
      significantly increased only production of IL-4 (P < .01) and IFN-gamma (P < .05)
      but not IL-5. Furthermore, IL-4 (P = .066) and IL-5 (P < .01) production in
      allergen-stimulated AM-CD4+ cell cocultures was higher in atopic asthmatic
      subjects but significantly lower in atopic nonasthmatic subjects (P < .05) as
      compared with the PMN-cocultures. For IFN-gamma, no difference was found between
      the AM and PMN cocultures in either atopic group. Allergen-stimulated IL-5
      production in coculture with both AMs and PMNs inversely correlated with both
      baseline FEV1 percent predicted and PD20 methacholine in atopic asthmatic
      subjects (P < .05, P < .01, or P < .001). CONCLUSION: These data suggest that AMs
      from atopic asthmatic subjects but not atopic nonasthmatic subjects, play a
      significant role in airway pathogenic immunity through enhancing TH2-type
      cytokine production.

PMID- 9768576
TI  - Expression of epithelial markers in nocturnal asthma.
AB  - BACKGROUND: Although the airway epithelium participates in inflammation and
      repair, the circadian expression of epithelial cell markers involved in these
      processes has not been investigated. OBJECTIVE: We sought to determine whether
      expression of CD51 (vitronectin and fibronectin receptor), CD54 (intercellular
      adhesion molecule-1), HLA-DR (activation marker), CD29 (beta1 integrin), CD49b
      (collagen receptor), and CD11b (complement receptor) exhibit a circadian rhythm
      in asthma. METHODS: Eleven patients with nocturnal asthma (NA), 9 subjects with
      nonnocturnal asthma (NNA), and 10 control subjects underwent bronchoscopy at 4 PM
      and 4 AM in a random order 1 week apart, with brushing of the proximal and distal
      airways. The percentage of cells staining for a particular marker was determined.
      RESULTS: At 4 PM, HLA-DR in the proximal airways and CD54 in the distal airways
      was significantly greater in control subjects as compared with asthmatic subjects
      (HLA-DR, control subjects: 10.0% [range, 5.0% to 21.0%]; NNA: 8.0% [range, 4.0%
      to 14.5%] NA: 3.5% [range, 2.0% to 6.0%], P = .01; CD54, control subjects: 17.0%
      [range, 8.0% to 25.0%], NNA: 8.0% [range, 5.3% to 11.5%], NA: 7.0% [range, 4.0%
      to 15.0%], P = .O;). At 4 AM, CD51 in the distal airways was significantly
      greater in patients with NA as compared with patients with NNA and control
      subjects (control subjects, 23.0% [range, 13.8% to 30.5%]; NNA, 32.0% [range,
      13.0% to 35.0%]; NA, 40.0% [range, 23.0% to 50.0%], P = .05). Expression of CD51
      in the distal airways correlated with the degree of airway obstruction (r = 
      0.57, P = .001). Control subjects exhibited significant circadian variation in
      the expression of HLA-DR in the proximal airways and CD54 in the distal airways.
      CONCLUSION: The increased CD51 at night in patients with NA may be related to
      increased airway inflammation and repair processes in response to injury. The
      circadian changes in CD54 and HLA-DR in control subjects require further study to
      determine their significance. (J Allergy Clin

PMID- 9768577
TI  - Association between Der p 1 concentration and peak expiratory flow rate in
      children with wheeze: a longitudinal analysis.
AB  - BACKGROUND: House dust mite (HDM) allergen exposure has been well documented as
      an environmental cause of airway hyperresponsiveness (AHR) and asthma symptoms.
      The relationship between asthma morbidity and exposure to low concentrations of
      HDM allergen suggests that there may be no safe exposure threshold to HDM
      allergen. OBJECTIVE: We aimed to investigate the associations between Der p 1 in
      bedding and lung function in 30 children with a history of wheezing in a
      longitudinal study. METHODS: After a cross-sectional study of school children,
      which included histamine challenge for AHR and skin testing for dust mite atopy,
      we made repeated measurements of HDM allergens in children with a history of
      wheeze over a 12-month period. These children also kept a daily asthma diary in
      which they recorded their peak expiratory flow rates (PEFRs). We used a repeated
      measures model to determine the association between PEFR and HDM allergen
      concentration. RESULTS: There was a significant association between PEFRs and HDM
      allergen concentration (beta-coefficient = -14.17, P = .0024) in children with
      HDM atopy. An association was not found in children without HDM atopy.
      CONCLUSIONS: These findings support the hypothesis that HDM allergens have an
      adverse effect on the lung function of children with wheeze and highlight the
      importance of maintaining low dust mite allergen levels throughout the year in
      the home environment of children sensitized to HDMs.

PMID- 9768578
TI  - Evaluation and treatment of allergic fungal sinusitis. I. Demographics and
      diagnosis.
AB  - BACKGROUND: Few cases of allergic fungal sinusitis have been systematically
      evaluated to conclusively confirm working clinical, histopathologic, and
      serologic diagnostic criteria. OBJECTIVES: The objective of this study was to
      describe 67 consecutive cases of allergic fungal sinusitis, the largest number of
      cases yet published. METHODS: Cases from 1 practice over 8 years were evaluated
      with a consistent protocol, including skin testing, serum chemistries and
      serologies, and surgical specimen analysis. RESULTS: All patients were atopic
      (100 %) and had nasal polyposis (100%). They tended to be young (33.3+/-13.1
      years, mean +/-SEM), immunocompetent (92 %; remaining 8 % with low quantitative
      immunoglobulin but normal function), have slight female preponderance (58%), have
      a history of hypertrophic rhinosinusitis (100%), report nasal cast production
      (75%), and have developed their disease in the southwestern United States.
      Bipolaris spicifera was the most prevalent fungus involved (67%). Total serum IgE
      (mean 668 IU/mL) and fungal-specific IgG were generally elevated, whereas fungal
      specific precipitins and specific IgE were generally negative despite positive
      fungal-specific immediate hypersensitivity skin tests. CONCLUSIONS: Patients with
      allergic fungal sinusitis tend to have elevated total serum IgE and fungal
      specific IgG at diagnosis but not fungal-specific IgE or precipitins.
      Histopathologic criteria for allergic fungal sinusitis diagnosis are discussed.
      The southwestern United States appears to be a "hot spot" for the disease,
      particularly caused by B spicifera.

PMID- 9768579
TI  - Evaluation and treatment of allergic fungal sinusitis. II. Treatment and follow
      up.
AB  - BACKGROUND: Previous allergic fungal sinusitis case reports have speculated that
      oral corticosteroids might reduce the severity of disease and possibly forestall
      the high rate of recurrent sinus surgery. OBJECTIVES: Our objective was to
      comprehensively review 67 consecutive cases of allergic fungal sinusitis for
      their response to treatment and the utility of monitoring patient serologies
      during clinical follow-up. METHODS: Allergic fungal sinusitis cases from a
      private practice were evaluated and treated with consistent diagnostic criteria
      and treatment paradigms. An 8-year retrospective review of serologic parameters
      and clinical response to treatment with or without oral corticosteroids is
      described. RESULTS: The total serum IgE was found to correlate with the clinical
      rhinosinusitis severity (P = .0002). The fungal-specific IgG also correlated with
      clinical rhinosinusitis severity but less rigorously (P = .004). An increase of
      10% or more in total serum IgE during follow-up was found to have significant
      predictive value for recurrent surgical intervention, with a sensitivity of 79%,
      specificity of 77%, positive predictive value of 48%, and negative predictive
      value of 93% (P < .0001). With the use of a modified corticosteroid treatment
      regimen adapted from allergic bronchopulmonary aspergillosis, as little as 2
      months of oral corticosteroids after surgery provided significant clinical
      improvement for up to 12 months (P < .0001), although patients taking 12 months
      of treatment fared the best clinically (P = .03). By survival analysis, oral
      corticosteroids prolonged the time between subsequent sinus surgeries (P = .01)
      in this highly recurrent disease. No significant side effects of oral
      corticosteroids were observed during treatment with this dosing regimen.
      CONCLUSIONS: Postoperative oral corticosteroids appear to be an effective
      treatment option for allergic fungal sinusitis, and monitoring of total serum IgE
      can be helpful in the clinical follow-up of these patients.

PMID- 9768580
TI  - Sinusitis in the common cold.
AB  - BACKGROUND: Acute community-acquired sinusitis is considered a bacterial
      complication of the common cold. Radiologic abnormalities in sinuses occur,
      however, in most patients with upper respiratory virus infections. OBJECTIVE:
      Assessment of the occurrence, clinical profile, laboratory findings, and outcome
      of radiologically confirmed sinusitis was carried out as part of a common cold
      study in young adults. METHODS: Clinical examinations and radiography of the
      paranasal sinuses were carried out on days 1, 7, and 21 in 197 patients with the
      common cold. The symptoms were recorded on diary cards on days 1 to 20. Ten
      viruses and 5 bacteria were studied as etiologic agents of common cold as
      reported earlier. Serum C reactive protein concentrations, erythrocyte
      sedimentation rates, and total white blood cell counts with differentials were
      determined in 40 randomized subjects on day 7. The effect of 6 days of intranasal
      fluticasone propionate treatment of the common cold in the prevention of
      sinusitis was analyzed. RESULTS: On day 7, 39% of patients with the common cold
      in the placebo group (n = 98) had sinusitis, which we would prefer to call viral
      sinusitis. The symptoms of patients with sinusitis and those without it were not
      clinically distinguishable. Viral infection was detected in 81.6% of patients
      with sinusitis. No significantly increased levels of antibodies to bacteria were
      detected. Serum C reactive protein concentrations, erythrocyte sedimentation
      rates, and white blood cell counts were low in patients with sinusitis. All
      patients made a clinical recovery within 21 days without antibiotic treatment.
      Fluticasone propionate treatment tended to prevent paranasal sinusitis,
      especially in rhinovirus-positive subjects. CONCLUSION: Viral sinusitis
      frequently occurs in the early days of the common cold, but it is a self-limited
      illness. The sinuses should not be imaged in patients with the common cold if the
      signs and symptoms of illness gradually become less severe and no specific signs
      suggestive of bacterial sinusitis occur.

PMID- 9768581
TI  - Validation of the Doser, a new device for monitoring metered-dose inhaler use.
AB  - BACKGROUND: Electronic monitoring of medication use has proved valuable in both
      clinical and research settings. The Doser, a new and inexpensive commercially
      available device for monitoring metered-dose inhaler (MDI) use, displays 3
      measures of daily use of an attached MDI: (1) the daily total of actuations, (2)
      the number of doses remaining in the MDI, and (3) the number of actuations on
      each of the preceding 30 days for later recall. OBJECTIVE: We sought to validate
      the accuracy of the Doser with several commonly prescribed MDIs. METHODS: In the
      laboratory, clinic personnel actuated an MDI with an attached Doser several times
      in succession on 3 consecutive days and recorded each of the 3 measures of MDI
      use (study 1). In study 2 clinic personnel carried an MDI and attached Doser with
      them for 4 weeks, actuating the MDI according to a prescribed protocol each
      morning and evening and again recording each of the 3 measures of daily use. In
      addition, during 2 weeks of study 2, a thermistor-based Nebulizer Chronolog was
      attached to the MDI to electronically record the date and time of each actuation.
      In study 3 clinic patients had both a Doser and Nebulizer Chronolog attached to
      their routinely used inhalers for 2 weeks and a Doser alone during a separate 2
      week period. RESULTS: In study 1 agreement was 99% to 100% among the 3 Doser
      measures, and each measure agreed with actual use by self-report 97% of the time.
      In study 2 agreement among the 3 Doser measures of use ranged from 98% to 99%.
      Agreement between each of the 3 Doser measures and the Nebulizer Chronolog ranged
      from 90% to 93%. Agreement between each of the 3 Doser measures and actual use
      ranged from 96% to 97%, and the Nebulizer Chronolog agreed with actual use 93% of
      the time. In study 3 Doser and Nebulizer Chronolog agreement with patient self
      report were 85% and 80%, respectively. Agreement between the Doser and Nebulizer
      Chronolog was 76%. Several failures of the thermistor-based Nebulizer Chronolog
      occurred, and occasional mechanical problems occurred with the Doser, primarily
      on particular types of MDI canisters. CONCLUSION: The Doser provides an accurate
      measure of MDI use with most commonly prescribed medications and may be useful
      for monitoring MDI use by investigators, clinicians, and patients.

PMID- 9768582
TI  - Ascaris-specific IgE and allergic sensitization in a cohort of school children in
      the former East Germany.
AB  - BACKGROUND: Helminthic infections induce an IL-4-dependent polyclonal stimulation
      of IgE synthetization. It is still unclear, however, what role helminths play in
      allergic sensitization. OBJECTIVE: We sought to determine the relationship
      between Ascaris-specific IgE and allergic sensitization in a nontropical country.
      METHODS: In 2 consecutive cross-sectional surveys in 1992-1993 and 1995-1996,
      data from school entrants (age range, 5 to 7 years), third graders (age range, 8
      to 10 years), and sixth graders (age range, 11 to 14 years) were collected. The 2
      younger groups were reexamined in the second survey. Data for about 2300
      children, including a cohort of 700 subjects, were analyzed. Ascaris IgE and
      total and specific IgE to inhalant allergens were measured, and skin prick tests
      were performed. Information about asthma and allergic rhinitis was collected by a
      questionnaire. RESULTS: Children who were Ascaris-IgE seropositive (>0.35 IU/mL)
      in both surveys had 10-fold higher levels of total IgE (451 IU/mL vs 45 IU/mL, P
      < .001) and higher prevalence rates of allergen-specific IgE seropositivity
      (56.3% vs 26.6%, P < .001). They also had a higher prevalence of allergic
      rhinitis (12.6% vs 3.7%, P < .001) and asthma (5.7% vs 1.6%, P < .05). In
      subjects who were Ascaris-seronegative in the first survey but seropositive in
      the second survey, total and specific IgE increased markedly. Sensitization to
      Dermatophagoides pteronyssinus increased nearly 3-fold in this group. In
      contrast, in children who became Ascaris-seronegative, total and specific IgE
      decreased. CONCLUSIONS: Contact with low doses of helminthic antigen is
      associated with an increase of total and specific IgE production. Helminthic
      infections in East German children are not the cause for a low prevalence of
      allergies in the former East Germany.

PMID- 9768583
TI  - Intravenous immunoglobulin inhibits IgE production in human B lymphocytes.
AB  - BACKGROUND: Intravenous immunoglobulin (IVIG) is commonly used as both an immune
      enhancing and immune-modulating agent. Treatment with high doses of IVIG
      diminishes IgE secretion in patients with severe steroid-dependent asthma.
      OBJECTIVE: We studied the action of IVIG on IgE production in highly purified B
      lymphocytes stimulated without additional T cells to determine the action of IVIG
      on B lymphocytes. METHODS: Human B cells were purified from tonsils, and T
      lymphocytes were removed by E-rosetting. B cells were cultured with IL-4 (400
      U/mL) and anti-CD40 antibodies (1 microg/mL?, with or without additional IVIG.
      Cell proliferation was determined by 3[H]-thymidine uptake, and supernatant IgE
      was determined by ELISA. Cell cycle analysis was performed by flow cytometry, and
      IgE transcripts were measured by in situ hybridization. RESULTS: IVIG (5 mg/mL)
      decreased B-cell proliferation in IL4/anti-CD40-stimulated B cells by an average
      of 74% (+/-6%). Addition of IVIG up to 48 hours after initiation of cell culture
      led to significant diminution of cell proliferation at 96 to 120 hours. This
      effect was dose dependent, with 10 mg/mL being the most effective and doses under
      0.1 mg/mL having minimal effect. IVIG diminished the number of stimulated cells
      progressing in the cell cycle by 30%, and there was no difference in cell
      viability between IVIG-treated and IVIG-untreated cells. The production of IgE in
      culture by anti-CD40/IL4-stimulated B lymphocytes was curtailed by greater than
      80% after addition of 5 mg/mL IVIG. This was associated with a decrease in IgE
      (epsilon) transcripts in IVIG-treated cultures. CONCLUSION: These data indicate
      that diminution of IgE production in anti-CD40/IL-4-stimulated B cells by IVIG is
      due to inhibition of early events related to proliferation and progression in the
      cell cycle.

PMID- 9768584
TI  - Reduced prevalence of allergic disease in patients with multiple sclerosis is
      associated with enhanced IL-12 production.
AB  - BACKGROUND: We previously showed that the prevalence of allergic disease is
      decreased in patients with multiple sclerosis (MS); however, the mechanisms that
      explain this finding have not previously been defined. OBJECTIVES: We have
      demonstrated that protection of patients with MS from allergic disease may be
      caused by the production in monocytes from these patients of elevated quantities
      of IL-12 compared with that observed in monocytes from individuals with
      allergies. METHODS: Purified monocytes from peripheral blood of subjects with or
      without allergies and from individuals with MS were directly stimulated with
      Staphylococcus aureus Cowan strain I in the absence of T cells. IL-12 was
      quantitated by a sensitive reverse transcription, competitive PCR. RESULTS: IL-12
      production was 5-fold greater in monocytes from patients with MS (n = 11) than
      that from individuals with allergies (n = 10) (for subjects with MS, 1.90+/-0.18
      vs 1.24+/-0.19 log10 fmol/microL for individuals with allergies) (P = .02).
      Although the production of IL-12 in monocytes from patients with MS was slightly
      higher than that from subjects without allergies, this difference was not
      statistically significant. CONCLUSIONS: IL-12 production in individuals with MS
      is much greater than in individuals with allergies. Because IL-12 induces TH1
      cytokine synthesis and reduces the production of TH2 cytokines, which amplify and
      prolong allergic inflammation, these studies suggest that enhanced IL-12
      production may protect individuals with MS from the development of allergy but
      may predispose such individuals toward autoimmune inflammation in the central
      nervous system.

PMID- 9768585
TI  - Genetic regulation of Dermatophagoides pteronyssinus-specific IgE responsiveness:
      a genome-wide multipoint linkage analysis in families recruited through 2
      asthmatic sibs. Collaborative Study on the Genetics of Asthma (CSGA).
AB  - BACKGROUND: Dermatophagoides pteronyssinus (Der p) is one of the most frequently
      implicated allergens in atopic diseases. Although HLA could play an important
      role in the development of the IgE response to the Der p allergens, genetic
      regulation by non-HLA genes influences certain HLA-associated IgE responses to
      complex allergens. OBJECTIVE: To clarify genetic control for the expression of
      Der p-specific IgE responsiveness, we conducted a genome-wide search for genes
      influencing Der p-specific IgE antibody levels by using 45 Caucasian and 53
      African American families ascertained as part of the Collaborative Study on the
      Genetics of Asthma (CSGA). METHODS: Specific IgE antibody levels to the Der p
      crude allergen and to the purified allergens Der p 1 and Der p 2 were measured.
      Multipoint, nonparametric linkage analysis of 370 polymorphic markers was
      performed with the GENEHUNTER program. RESULTS: The best evidence of genes
      controlling specific IgE response to Der p was obtained in 2 novel regions:
      chromosomes 2q21-q23 (P = .0033 for Caucasian subjects) and 8p23-p21 (P = .0011
      for African American subjects). Three regions previously proposed as candidate
      regions for atopy, total IgE, or asthma also showed evidence for linkage to Der p
      specific IgE responsiveness: 6p21 (P = .0064) and 13q32-q34 (P = 0.0064) in
      Caucasian subjects and 5q23-q33 (P = 0.0071) in African American subjects.
      CONCLUSIONS: No single locus generated overwhelming evidence for linkage in terms
      of established criteria and guidelines for a genome-wide screening, which
      supports previous assertions of a heterogeneous etiology for Der p-specific IgE
      responsiveness. Two novel regions, 2q21-q23 and 8p23-p21, that were identified in
      this study merit additional study.

PMID- 9768586
TI  - Linkage analysis of Dermatophagoides pteronyssinus-specific IgE responsiveness
      with polymorphic markers on chromosome 6p21 (HLA-D region) in Caucasian families
      by the transmission/disequilibrium test. Collaborative Study on the Genetics of
      Asthma (CSGA).
AB  - BACKGROUND: Recently, we have obtained evidence for linkage between Der p 1
      specific IgE antibodies and markers on chromosome 6p21 (HLA-D region) in a genome
      wide screening in Caucasian families recruited as a part of the Collaborative
      Study on the Genetics of Asthma (CSGA). OBJECTIVE: Specific IgE antibodies toward
      different Dermatophagoides pteronyssinus (Der p) polypeptides were detected by
      immunoblotting analysis, and the transmission/disequilibrium test (TDT) was
      performed between specific IgE responsiveness toward each different Der p
      polypeptide and markers on chromosome 6p21 to better clarify the genetic
      contribution of HLA-D genes. METHODS: We studied 299 individuals in 45 Caucasian
      families participating in the CSGA. Serum samples from 137 individuals that
      showed elevated specific IgE antibodies toward the Der p crude allergen (> -0.5
      log IU/mL) by ACCESS immunoassay were subjected to immunoblotting analysis. TDT
      was conducted between the presence of specific IgE antibodies toward each of 12
      different Der p polypeptides and 4 polymorphic markers on chromosome 6p21.
      RESULTS: The 196-bp allele of D6S1281 and the 104-bp allele of DQCAR showed
      significant excess transmission to specific IgE responders toward a particular
      Der p polypeptide (120 kd, 55 kd, 45 kd, or 37 kd). In contrast, the 200-bp
      allele of D6S1281 and the 204-bp allele of D6S291 showed significantly decreased
      transmission to specific IgE responders toward a particular Der p polypeptide
      (120 kd, 90 kd, 52 kd, or 45 kd). Deviation from the expected 50% transmission in
      heterozygous parents was statistically significant after correcting for multiple
      comparisons. CONCLUSION: This study supported our previous findings that genes on
      chromosome 6p21 (HLA-D region) may influence the expression of Der p-specific IgE
      responsiveness in this Caucasian population. Our results, however, reveal the
      complexity of genetic regulations of Der p-specific IgE responsiveness by HLA-D
      genes, suggesting the strong influence of non-HLA loci and perhaps environmental
      factors for the development of Der p-specific IgE responsiveness.

PMID- 9768587
TI  - Genetic influences of chromosomes 5q31-q33 and 11q13 on specific IgE
      responsiveness to common inhaled allergens among African American families.
      Collaborative Study on the Genetics of Asthma (CSGA).
AB  - BACKGROUND: We have recently conducted a genome-wide screening for genes
      influencing Dermatophagoides pteronyssinus-specific IgE responsiveness as a part
      of the Collaborative Study on the Genetics of Asthma (CSGA), which showed
      evidence for linkage in some regions, including chromosomes 5131-q33 and 11q13 in
      African American families. OBJECTIVES: To clarify relative contributions of these
      regions to atopy in the same African American population, we have conducted
      further genetic linkage studies of specific IgE responses toward common inhaled
      allergens. METHODS: We studied 328 individuals in 58 African American families
      participating in the CSGA. Specific IgE responses toward Dermatophagoides
      farinae, cat, dog, American cockroach, rye grass, and Bermuda grass, as measured
      by skin tests, were used for multipoint linkage analysis with polymorphic markers
      on chromosomes 5q31-q33 and 11q13. RESULTS: Specific IgE response toward American
      cockroach showed evidence for linkage to chromosomes 5q31-q33 (P = .0050) and
      11q13 (P = .017). Specific IgE response toward dog showed evidence for linkage
      with chromosome 5q31-q33 (P = .0043). Evidence for linkage with chromosome 11q13
      was obtained for specific IgE responses toward Dermatophagoides farinae (P =
      .012), cat (P = .035), and Bermuda grass (P = .017). The presence of a positive
      ST response for at least 1 of 30 common allergens showed evidence for linkage to
      chromosomes 5q31-q33 (P = .017) and 11q13 (P = .00058). CONCLUSIONS: These data
      support that genes on both chromosomes 5q31-q33 and 11q13 confer susceptibility
      to upregulated IgE-mediated immune responses in this African American population.
      The putative genes on chromosomes 5q31-q33 and 11q13, however, showed contrasting
      effects on atopy, which may result from strong gene-environmental interactions.

PMID- 9768588
TI  - Nerve growth factor is preformed in and activates human peripheral blood
      eosinophils.
AB  - BACKGROUND: Recent studies have shown that nerve growth factor (NGF) is produced
      by and can act on several immune-inflammatory cells. OBJECTIVES: The objective of
      this study was to study the effects of NGF on human peripheral blood eosinophils
      and assess whether these cells produce and store NGF. METHODS: Eosinophils were
      purified by negative immunoselection (magnetic cell sorting systems, purity 98%
      to 100%) from 13 subjects (9 to 26 years old) with mild blood eosinophilia,
      mainly of allergic origin. Eosinophils were incubated with NGF (50 to 1000
      ng/mL), and supernatants were collected for measurement of eosinophil peroxidase
      (EPO, 20 minutes, colorimetric enzymatic assay) and IL-6 (12 hours, ELISA).
      Eosinophil viability was evaluated by Trypan blue test (days 2, 3, and 4). NGF
      content in freshly isolated eosinophils, after ultrasound disruption, was
      determined with a 2-site immunoenzymatic assay. The presence of mRNA for NGF was
      evaluated by reverse transcription PCR. RESULTS: NGF caused EPO release (highly
      significant at 1000 ng/mL NGF). IL-6 release from eosinophils was not higher than
      IL-6 spontaneously released into culture medium alone. NGF did not significantly
      affect the number of viable eosinophils. NGF was found in the eosinophil
      sonicates (1.5 to 17.8 pg/mL per 106 cells). Similarly, mRNA for NGF was detected
      by reverse transcription PCR in the freshly isolated eosinophils. CONCLUSIONS:
      NGF activates human peripheral blood eosinophils from subjects with mild
      eosinophilia to selectively release inflammatory mediators. Eosinophils store and
      produce NGF. Therefore the capability of NGF to induce a secretory response and
      its production and storage by circulating human eosinophils suggest a possible
      role for NGF in conditions associated with eosinophilia, including allergic
      disease.

PMID- 9768589
TI  - Adhesion molecule expression on skin endothelia in atopic dermatitis: effects of
      TNF-alpha and IL-4.
AB  - BACKGROUND: Atopic dermatitis (AD) is characterized by skin infiltrates of
      leukocytes, such as lymphocytes and eosinophils. OBJECTIVE: To describe the
      mechanisms determining this inflammatory process, we have analyzed expression of
      adhesion molecules and their regulation on skin endothelial cells (ECs). METHODS:
      Expression of adhesion molecules on ECs was analyzed by immunohistochemistry by
      using Ulex europaeus agglutin 1 as a pan-endothelial marker. RESULTS: Vascular
      cell adhesion molecule-1 (VCAM-1), E-selectin, and P-selectin were not found in
      skin of nonatopic individuals, whereas expression of these surface molecules was
      observed in nonlesional skin of patients with AD and was even more pronounced in
      lesional skin or after epicutaneous application of aeroallergen. Induction of
      adhesion molecule expression was examined on both macrovascular ECs from human
      umbilical cord vein (HUVECs) and human microvascular ECs (HMEC-1) from skin. TNF
      alpha very potently upregulated adhesion molecule expression in vitro on both EC
      cell types. To verify the in vivo relevance of TNF-alpha, we performed TNF-alpha
      staining in the skin. TNF-alpha was observed in the dermis of nonatopic skin,
      both in chymase-containing mast cells and CD68+ macrophages. The increase in the
      number of TNF-alpha-containing cells was concomitant with the increase in
      adhesion molecule expression in the skin of patients with AD. IL-4 is supposed to
      be important in atopic diseases because of its IgE- and VCAM-1-inducing
      properties. However, IL-4 addition failed to induce VCAM-1 expression on HMEC-1,
      although in the same set of experiments, a clear induction of VCAM-1 expression
      by IL-4 on HUVECs was demonstrated. Flow cytometry revealed the absence of 11-4
      receptor alpha-chains on HMEC-1 and their presence on HUVECs.
      Immunohistochemistry examination on skin sections showed no binding of the IL-4R
      alpha-chain antibodies to ECs. CONCLUSION: We conclude that adhesion molecule
      expression is increased in the skin of patients with AD. Most probably, this
      increased expression is not a (direct) effect of IL-4 on skin endothelium, but
      other cytokines, such as TNF-alpha, might be responsible for this increased
      adhesion molecule expression. Continuous adhesion molecule expression may
      facilitate T-cell extravasation in a nonantigen-specific manner, thus explaining
      the presence of increased T-cell numbers in nonlesional skin of patients with AD.

PMID- 9768590
TI  - The latex allergen Hev b 5 transcript is widely distributed after subcutaneous
      injection in BALB/c mice of its DNA vaccine.
AB  - BACKGROUND: DNA vaccines reduce IgE responses to selected allergens, but severe
      reactions to the expressed antigen may limit the usefulness of the technique in
      allergen immunotherapy. OBJECTIVE: We sought to determine the extent of spread of
      an injected DNA vaccine in mice. METHODS: We placed the gene encoding the potent
      Hevea latex allergen Hev b 5 in a mammalian expression vector and injected this
      DNA vaccine subcutaneously into BALB/c mice. At several times after injection,
      the presence of Hev b 5 transcript was determined in multiple tissues by RT-PCR.
      The identity of the amplification product was confirmed by Southern hybridization
      and restriction analyses. RESULTS: Hev b 5 RNA appeared at the injection site and
      in the lymph nodes, spleen, and lungs within 1 day after injection and persisted
      for at least 14 days. Hev b 5 RNA was also identified in the blood and tongue 14
      days after injection. Antibody and cell-mediated responses to Hev b 5 were also
      noted in the immunized animals at later time points. As expected, animals
      injected with the identical plasmid containing the Hev b 5 DNA in the antisense
      orientation mounted no immune response to Hev b 5. CONCLUSIONS: The rapid and
      widespread appearance of the Hev b 5 transcript in the injected mice confirms
      that DNA is translocated from the injection site, transcribed, and expressed in
      immune and nonimmune tissues after injection. Controlling the extent and degree
      of expression in specific target tissues may allow therapeutic DNA vaccination
      with plasmids that encode potentially toxic allergens.

PMID- 9768591
TI  - Identification of hevein (Hev b 6.02) in Hevea latex as a major cross-reacting
      allergen with avocado fruit in patients with latex allergy.
AB  - BACKGROUND: Recent studies demonstrated that allergy to natural rubber latex is
      frequently associated with hypersensitivity to avocado fruit. The responsible
      cross-sensitizing allergen has not been identified. OBJECTIVE: The purpose of
      this study was to investigate the cross-reactivity of a latex major allergen,
      hevein, with avocado proteins. METHODS: Serum samples from 118 health care
      workers (HCWs) allergic to latex (HCW group) and 78 patients with spina bifida
      (SB) allergic to latex (SB group) were included in this study. Anti-hevein and
      anti-avocado IgE antibodies were measured by enzyme-linked allergosorbent assay.
      Cross-reactivity of hevein to avocado proteins was assessed by inhibition of the
      IgE binding in individual patients' sera containing IgE antibodies to both hevein
      and avocado. RESULTS: The prevalence of seropositive IgE antibodies to avocado
      was found to be strongly associated with the presence of hevein-specific IgE
      antibodies in subjects of both groups (P < .001). Sixty-seven of 91 (73%)
      subjects from the HCW group and all 19 subjects in the SB group with positive IgE
      antibodies to hevein also had elevated IgE values to avocado. Competitive RAST
      inhibition with 42 sera showed that IgE binding to avocado could be completely
      inhibited in 27 (64%) sera by preincubation with hevein. By contrast, the degrees
      of inhibition of IgE to hevein by avocado extract ranged from 0% to 36% (n = 16).
      These results indicate that sensitization to avocado in most patients allergic to
      latex is caused exclusively by IgE-binding epitopes present in hevein. Results of
      immunoblots and immunoblot inhibition with 11 serum samples confirmed that a 30
      kd protein in avocado was the major IgE-binding component; the IgE-binding
      reactivity to this protein could be inhibited by hevein in all sera tested.
      CONCLUSION: Hevein is the major cross-reacting allergen with avocado in subjects
      with latex allergy.

PMID- 9768592
TI  - Diagnosis of natural rubber latex allergy: multicenter latex skin testing
      efficacy study. Multicenter Latex Skin Testing Study Task Force.
AB  - BACKGROUND: No characterized diagnostic natural rubber latex skin testing
      material is licensed for use in the United States. OBJECTIVE: We have conducted a
      multicenter clinical skin testing study to document the safety and diagnostic
      sensitivity and specificity of a candidate Hevea brasiliensis nonammoniated latex
      (NAL) extract. These data are intended to support the licensing of this reagent
      for the diagnosis of latex allergy in high-risk populations. METHODS: Three
      hundred twenty-four subjects (304 adults and 20 children) were classified by
      their clinical history as having latex allergy (LA group, 124 adults and 10
      children) or having no latex allergy (NLA group, 180 adults and 10 children). All
      subjects provided blood samples and then received sequential puncture skin tests
      (PSTs) at 1, 100, or 1000 microg/mL protein with a bifurcated needle and NAL
      (Greer Laboratories) from Malaysian Hevea brasiliensis (clone 600) sap. A 2-stage
      glove provocation test was used to clarify latex allergy status of individuals
      with positive history/negative PST result and negative history/positive PST
      result mismatches. RESULTS: Twenty-four subjects (15%) originally designated as
      having LA on the basis of their initial clinical history were reclassified to the
      NLA group on the basis of a negative glove provocation test result. Of the 134
      subjects with LA, 54 (40%) were highly sensitive to latex, with a positive PST
      result at 1 microg/mL NAL. The Greer NAL reagent produced a positive PST rate
      (sensitivity) of 95% and 99% in subjects with LA at 100 microg/mL and 1 mg/mL,
      respectively. The negative PST rate (specificity) in 190 subjects with a negative
      history with the NAL extract at 100 microg/mL and 1 mg/mL, was 100% and 96%,
      respectively. Immediately after the PST, mild systemic reactions (mainly
      pruritus) were recorded in 16.1 % of the adults in the LA group and 4.4% of the
      adults in the NLA group. No reactions required treatment with epinephrine. Only
      mild delayed reactions were observed in 9.6% (LA group) and 2.8% (NLA group) of
      subjects 24 to 48 hours after PST. Mean wheal and erythema diameters measured in
      the 10 children in the LA group with spina bifida at 100 microg/mL and 1 mg/mL
      were similar to those observed in the adults in the LA group, suggesting that
      children are not at increased risk for systemic reactions compared with adults.
      CONCLUSIONS: A suggestive clinical history is necessary but not sufficient for a
      definitive diagnosis of IgE-dependent latex allergy. These data support the
      safety and diagnostic efficacy of the Greer NAL, skin test reagent at 100
      micro/mL and 1 mg/mL for confirmatory PSTs.

PMID- 9768593
TI  - Human mast cells produce IL-13 by high-affinity IgE receptor cross-linking:
      enhanced IL-13 production by IL-4-primed human mast cells.
AB  - BACKGROUND: Mast cells play a central role not only in the early phase of the
      allergic reaction, but also participate in the late phase of the allergic
      reaction through the allergen and IgE-dependent release of multifunctional
      cytokines. OBJECTIVE: Using the recently established culture system for human
      mast cells, we examined the expression of a variety of cytokines in cord blood
      derived human cultured mast cells (HCMCs) in response to different stimuli.
      METHODS: HCMCs were grown from cord blood mononuclear cells in the presence of
      stem cell factor and IL-6 for 10 weeks. Cytokine mRNA expression in HCMCs by the
      different stimuli was examined by RT-PCR. Then taking 2 important cytokines, IL
      13 and IL4, that share several functional properties and play important roles in
      allergic diseases, we examined protein as well as mRNA expression of both
      cytokines in HCMCs. RESULTS: HCMCs did not express either IL-13 or IL-4
      spontaneously. Stimulation with PMA + A23187 induced the expression of IL4
      protein, as well as IL-13 protein, in their cytoplasm, although IL-4 secreted in
      the supernatant was below detectable levels in contrast to a significant amount
      of IL-13. Stimulation of HCMCs by cross-linking of the high-affinity IgE receptor
      (Fc(epsilon)RI) induced the expression of IL-13 mRNA and protein, but not IL4.
      Although we previously found that IL-4 upregulates Fc(epsilon)RI expression on
      HCMCs, when HCMCs were first cultured in the presence of IL4 and then activated
      through FC(epsilon)RI cross-linking, remarkable increase was found in IL-13
      production. Furthermore, although IL-4 was still undetectable at protein level,
      IL-4 mRNA expression was induced in the IL-4-primed HCMCs stimulating
      Fc(epsilon)RI cross-linking. In addition, we examined the effects of these
      cytokines on the surface molecule expression in HCMCs. Although IL4 remarkably
      upregulated lymphocyte function-associated antigen-1, intercellular adhesion
      molecule-1, and Fc(epsilon)RI expression and downregulated c-kit expression in
      HCMCs, IL-13 did not. CONCLUSIONS: Our observation that HCMCs produce IL-13 on
      cross-linking of Fc(epsilon)RI, which was enhanced by IL-4 priming, supports an
      important role of mast cells in amplification of allergic reaction and further
      suggests one of the mechanisms enhancing mast cell function in the
      microenvironment.

PMID- 9768594
TI  - Analysis of cytokine signaling in patients with extrinsic asthma and
      hyperimmunoglobulin E.
AB  - BACKGROUND: Recent data suggest that the regulation of class switching to IgE by
      cytokines is mediated by STAT transcription factors. The induction of IgE by IL-4
      and IL-13 occurs through the activation of the intracellular signal-transducing
      protein Stat6, whereas the inhibition of IgE class switching by interferon-y (IFN
      gamma) occurs through the activation of Statl. OBJECTIVE: We hypothesized that in
      extrinsic asthma or in cases of markedly elevated IgE (ie, hyperimmunoglobulin E
      [HIE]) increased levels of IgE may be associated with alterations in the cytokine
      levels or the activation of Stat6. METHODS: PBMCs and sera from 8 patients with
      extrinsic asthma (mean IgE, 285+/-100 IU/mL), 3 patients with HIE (mean IgE,
      7050+/-1122 IU/mL), and 14 nonatopic control subjects (mean IgE, 112+/-28 IU/mL)
      were analyzed. RESULTS: The mean IL-4 level detected by ELISA was much greater in
      patients with HIE than control subjects (88.6+/-11.5 pg/mL vs 11.5+/-7.1 pg/mL, P
      = .005), and increased IL-4 levels among patients with both asthma and HIE
      correlated with the increased IgE levels. In contrast, IL-13 levels were not
      elevated. Levels of Stat6 protein present in PBMCs did not differ in the patients
      and control subjects. Examination of Stat6 DNA-binding activity demonstrated no
      activation of IL-4 signaling in patients with either HIE or acute asthma.
      Interestingly, evidence for the presence of B cells that have already switched to
      IgE was seen in PBMCs of several patients with asthma or HIE. CONCLUSION: These
      results indicate that (1) IgE production in asthma and HIE usually is associated
      with elevated levels of IL-4, but not IL-13, in the peripheral blood; (2) the
      increased sera IL-4 levels in asthma and HIE are not sufficient to induce Stat6
      activation in PBMCs; and (3) evidence of switch recombination to epsilon may be
      detected in isolated cases of elevated IgE. This implies that high levels of IgE
      in these patients either results from B cells that have already undergone class
      switching, from Ig class switching that is localized to target tissues, or both.

PMID- 9768595
TI  - Phosphorylation of cytosolic phospholipase A2 by IL-3 is associated with
      increased free arachidonic acid generation and leukotriene C4 release in human
      basophils.
AB  - BACKGROUND: Human basophils secrete leukotriene C4 (LTC4) in response to various
      stimuli, and a short treatment with IL-3 enhances LTC4 release, although IL-3
      alone does not induce LTC4 release. However, the mechanism of this priming effect
      of IL-3 for LTC4 generation remains unknown in human basophils. OBJECTIVE: This
      study was designed to explore the mechanisms by which short treatments with IL-3
      enhance stimulated secretion of LTC4, with a focus on the activation of cytosolic
      phospholipase A2 (cPLA2). METHODS: The phosphorylation state of cPLA2 in human
      basophils was examined by its shift in electrophoretic mobility as detected by
      Western blotting. Free arachidonic acid (AA) and LTC4 were measured by gas
      chromatography-negative ion chemical ionization mass spectrometry and LTC4
      specific RIA, respectively. RESULT: Human basophils expressed cPLA2. IL-3, as
      well as the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate,
      caused a shift in the electrophoretic mobility of cPLA2, which indicated
      phosphorylation of cPLA2 and therefore its activation. Ionomycin at a
      concentration of 0.1 microg/mL was used to induce a modest elevation of cytosolic
      calcium response ([Ca2+]I), no apparent cPLA2 phosphorylation, and little free AA
      and LTC4 generation. Pretreatment with IL-3 (1 to 10 ng/mL) markedly enhanced
      ionomycin (0.1 microg/mL)-mediated AA and LTC4 generation. The concentration
      dependence of cPLA2 phosphorylation by IL-3 and its effects on free AA and LTC4
      generation were similar. The selective PKC inhibitors, bis-indolylmaleimide II
      and Ro-31-8220 inhibited the phorbol 12-myristate 13-acetate-mediated cPLA2
      electrophoretic mobility shift, but not the IL-3-mediated shift, suggesting that
      the IL-3 effect is PKC independent. Both the anaphylatoxin split product of the C
      component C5 (C5a) and f-Met-Leu-Phe induced PKC-independent cPLA2
      phosphorylation with a similar time course most notable for the absence of
      observable changes in cPLA2 phosphorylation before 30 seconds. These results
      suggested an explanation for the absence of free AA generation by C5a. When
      [Ca2+]I was elevated in response to C5a, there was no phosphorylation of cPLA2,
      and by the time cPLA2 became phosphorylated, [Ca2+]I had returned to resting
      levels. Treatment with IL-3 preconditioned the cPLA2 by causing its
      phosphorylation so that the transient [Ca2+]I response, which followed
      stimulation by C5a, could induce the generation of free AA and LTC4. CONCLUSION:
      Taken together, these results suggest that the effect of IL-3 for free AA
      generation and LTC4 release might be due to induction of cPLA2 phosphorylation.
      The studies demonstrated a need for synchronous cPLA2 phosphorylation and
      elevations in [Ca2+]I.

PMID- 9768596
TI  - Effect of angiotensin II receptor blockade on bronchial responsiveness in
      asthmatic subjects.

PMID- 9768597
TI  - Cytogenetic abnormalities and their lack of relationship to the Asp816Val c-kit
      mutation in the pathogenesis of mastocytosis.

PMID- 9768598
TI  - A survey of Epi-PEN use in patients with a history of anaphylaxis.

PMID- 9768599
TI  - Near-fatal anaphylaxis after Hymenoptera venom immunotherapy.

PMID- 9768600
TI  - Chloroflourocarbon- and hydrofluoroalkalane-cromolyn sodium for asthma: the issue
      of equivalence trials.

PMID- 9768601
TI  - Burn treatment.

PMID- 9768602
TI  - Use of sponges during laparoscopic surgery.

PMID- 9768603
TI  - George Adlington Syme Oration. The surgeon as a leader in cancer care.

PMID- 9768604
TI  - Evaluation of 250 free-flap reconstructions after resection of tumours of the
      head and neck.
AB  - BACKGROUND: Microvascular free-tissue transfer is now the primary method of
      reconstruction in many centres. The aim of this study was to evaluate the
      applications, complications and limitations of free-flap reconstruction in a
      series of patients with tumours of the head and neck. METHODS: This study
      reviewed prospectively accessioned computerized records in a dedicated head and
      neck database. Patients treated between 1987 and 1995 with a minimum of a 1-year
      follow-up were reviewed. There were 242 patients with a mean age of 58 years (172
      men and 70 women). The most common tumour sites were oral cavity (42%),
      oropharynx (32%) and hypopharynx (11%). Mucosal squamous carcinoma accounted for
      87% of primary cancers. RESULTS: Among the 250 free flaps, the radial forearm
      flap (205) and free jejunum (25) predominated. There were 21 episodes of vascular
      occlusion (8%), failure of 10 flaps (4%) and two patients died peri-operatively
      (0.8%). A second free flap was used in five of 10 cases of flap failure. The
      fistula rate was 4.4% among 203 patients at risk for this complication, which
      comprised four of 178 forearm flaps and five of 25 free jejunal grafts. Four of
      16 jaw reconstructions failed. CONCLUSIONS: A 96% success rate was achieved using
      free-tissue transfer for head and neck reconstruction. The overall complication
      rate was low but jaw reconstruction and free jejunal grafts posed the greatest
      problems because of failure of radial bone and fistulas, respectively. The radial
      forearm septocutaneous flap was very reliable and remains our mainstay for oral
      reconstruction.

PMID- 9768605
TI  - Clinical and radiological predictors of complete excision in breast-conserving
      surgery for primary breast cancer.
AB  - BACKGROUND: Local recurrence after conservative surgery for breast cancer usually
      results from growth of residual cancer adjacent to the excised primary tumour or
      from multicentric disease. Complete local excision (CLE) confirmed histologically
      is essential to ensure that the risk of local recurrence is minimal. This study
      was undertaken to determine that clinical or radiological factors may assist the
      surgeon at the time of surgery to achieve this aim. METHODS: A retrospective
      review of 101 cases treated by conservative surgery identified 70 cases of CLE
      and 31 of incomplete local excision (ILE). Clinical, surgical and
      histopathological data were taken from hospital records. Mammographic features
      and those of specimen X-rays were evaluated without knowledge of the
      histopathological outcome of surgery. RESULTS: Complete excision was
      significantly associated with type of operation (lumpectomy vs wide local
      excision/quadrantectomy, P < 0.003), absence of calcification (P < 0.03) and the
      presence of a mass on mammography (P = 0.05). Tumour size (> 2.5 cm) and the
      presence of extensive ductal carcinoma in situ (DCIS) were associated with
      incomplete excision (P = 0.0005). No relationship was demonstrated with patient
      age, breast size, breast density, tumour grade, receptor status, axillary nodal
      status or spicules on X-ray and completeness of excision. Specimen X-ray had a
      positive predictive value of 94% with CLE. CONCLUSIONS: Clinical and pre
      operative mammographic parameters are important for predicting CLE for breast
      cancers treated by breast-conserving surgery. Specimen radiology for palpable
      lesions can confirm excision of the cancer and permit re-excision of breast
      tissue at the time of initial surgery. Its role in determining CLE should be
      further evaluated.

PMID- 9768606
TI  - The potential impact of breast cancer screening in Hong Kong.
AB  - BACKGROUND: Breast cancer is the second most common cancer and cause of death in
      women from Hong Kong. The Well Women Clinic at Kwong Wah Hospital offers breast
      cancer screening (physical examination and mammography) for women over 40 years
      of age. METHODS: Results of screening over a 2-year period revealed an overall
      malignancy detection rate of 2.6 per 1000 screens with a strong selection bias
      for symptomatic women. RESULTS: Screening only slightly increased the proportion
      of stage I cancers detected; of the malignancies detected, a significant
      percentage were in situ cancers with doubtful effects on breast cancer mortality.
      Teamwork and communication were useful in keeping a low referral rate to the
      surgical clinic of 6.1%, as well as a low biopsy rate for mammographic
      abnormalities. CONCLUSIONS: A re-evaluation of the real risk of breast cancer in
      young women together with the lack of proven value from screening has suggested a
      need for reconsideration of offering screening to women 40 years and over in Hong
      Kong.

PMID- 9768607
TI  - Carcinoma of the male breast: a review and recommendations for management.
AB  - BACKGROUND: Male breast cancer is rare and experience of it in any single
      institution is limited. The aim of this study was to evaluate the presentation,
      management and outcome of male patients with breast cancer treated at Concord
      Repatriation General Hospital hospital over a 38-year period and to determine a
      best-practice protocol based on the results and a review of the literature.
      METHODS: A total of 42 patients were retrospectively reviewed, pathology slides
      were re-examined and reclassified where necessary. Outcome was assessed and
      compared with results obtained from a literature review. RESULTS: A trend towards
      less radical surgery has emerged. Overall 5-year survival was 50%, but, due to
      the late age at presentation, more than half the deaths were non-breast cancer
      related. One quarter of the patients presented with locally advanced or
      metastatic disease. CONCLUSIONS: The presentation, diagnosis pathology and
      outcome of breast cancer are similar in men and women, although the disease
      occurs at a later age in men. Radical surgery is not required in order to gain
      local control, but knowledge of axillary node status is important in determining
      prognosis and the need for adjuvant therapy.

PMID- 9768608
TI  - One hundred liver resections including comparison to non-resected liver-mobilized
      patients.
AB  - BACKGROUND: Factors of liver resection associated with postoperative recovery and
      survival, the modalities that affect survival with resected colorectal carcinoma
      liver metastases, the comparison of liver function of liver-resected to liver
      mobilized but not resected patients, and observation of early liver regeneration
      volume over time have not been studied prospectively. This study aimed to
      prospectively analyse these factors. METHODS: Data were collected prospectively
      on 100 consecutive liver resections, and 10 liver-mobilized but not resected
      patients by the Hepatobiliary Unit, University of Melbourne, Austin Campus.
      Follow-up of patients was 100%. RESULTS: The factors associated with blood loss
      were the type of liver resection (P = 0.0001), the length of the operation (P =
      0.0001) and a central venous pressure greater than 5 cm of water (P = 0.0008). An
      inverse correlation existed between blood loss and long-term survival (P =
      0.003). The only predictor for a postoperative complication was the length of the
      operation (P = 0.03): a correlation of moderate significance existed between
      blood loss and a complication (P = 0.052; confidence interval 0.19-1.17). The 5
      year cumulative survival for hepatic resection for colorectal carcinoma Dukes A +
      B was 55%; there was a significantly better survival of Dukes A + B compared to
      Dukes C (P = 0.03) and also for those 50 years or older, but this did not depend
      on whether there were one or more lesions present. Resected patients had a
      significantly higher alanine transaminase (ALT), total bilirubin and
      international normalized ratio than non-resected patients, but not albumin, total
      protein, alkaline phosphatase or aspartate aminotransferase. The serum albumin
      fall was similar in both groups, which indicated that loss of liver tissue was
      not the cause. The re-resection rate was 8% without mortality and with low
      morbidity. Liver volume was restored by 64% (510 +/- 170 cc) by 7 days
      postoperatively. CONCLUSIONS: Major hepatic resection can be performed with low
      mortality, morbidity and short hospital stay, with a 5-year survival for
      colorectal carcinoma better than 50%. Resection needs to be considered more
      frequently for curative management. Serum albumin fall is not caused by loss of
      liver tissue and blood loss can be controlled by central venous pressure
      manipulation and vascular isolation. Re-resection is a safe and rewarding
      treatment and needs to be planned at the first resection.

PMID- 9768609
TI  - Patterns of serum CEA fall after hepatic arterial chemotherapy as sole therapy
      and combined with cryotherapy for colorectal metastases.
AB  - BACKGROUND: Hepatic artery chemotherapy (HAC) and cryoablation are treatments for
      unresectable liver metastases from colorectal carcinomas. Our centre has
      previously published data that describe survival statistics of patients after
      each of these treatments. It has also been established that serial serum
      carcinoembryonic antigen (CEA) concentrations may be used to monitor disease
      progress, and that the magnitude of fall is prognostic for both treatments. The
      pattern of fall of CEA following cryotherapy and regional chemotherapy has not
      previously been compared. METHODS: In this study, we examined 26 HAC patients and
      24 cryotherapy patients. RESULTS: The mean percentage of the pre-treatment CEA
      concentration for the HAC group was 60.5% at 50 days and 29.4% at 150 days, and
      for the cryotherapy group 24.9% at 50 days and 24.3% at 150 days. Calculating the
      difference between means revealed a significantly different mean fall in the
      cryotherapy group at 50 days (P < 0.001) and a difference in mean fall at 150
      days (P > 0.1) which was not significant. In patients who responded to hepatic
      artery chemotherapy, the eventual CEA fall was very similar in magnitude.
      CONCLUSIONS: The pattern of fall of CEA differs in these two treatments.

PMID- 9768610
TI  - Cryotherapy of the resection edge after liver resection for colorectal cancer
      metastases.
AB  - BACKGROUND: An involved or inadequate (< 1 cm) resection margin is associated
      with a high rate of local tumour recurrence and reduced survival rates after
      liver resection for colorectal metastases. This paper assesses whether or not
      hepatic cryotherapy of the resection edge is suitable to improve local disease
      control. METHODS: From April 1990 to May 1997, we performed cryotherapy of the
      resection edge in 44 patients after liver resection for colo rectal liver
      metastases with an involved or inadequate resection margin. The reasons for
      performing edge cryotherapy instead of extension of resection were: proximity of
      hepatic veins or portal sheath (n = 12); avoidance of extended left or right
      hemihepatectomy (n = 15); inadequate liver tissue reserve after resection (n =
      16); and patient unfit to undergo further major resection (n = 1). Histological
      examination showed the resection margin to be involved in 24 patients and close
      (< 1 cm) in 20 patients. RESULTS: Two patients died after surgery. Morbidity
      consisted of intra-abdominal collections (n = 6), postoperative bleeding (n = 1),
      wound infection (n = 1) and transient liver failure (n = 1). At a median follow
      up of 19 months, 16 patients are alive and disease-free, 26 patients developed
      recurrence and 15 of them died. Nineteen patients developed recurrence which
      involved the liver but only five of these were at the resection edge. Median
      overall and liver disease-free survival was 33 and 23 months, respectively.
      CONCLUSIONS: Cryotherapy of the resection edge after resection of colorectal
      liver metastases with involved or inadequate resection margins considerably
      improves local disease control and may allow a greater proportion of patients
      with liver metastases to undergo potentially curative treatment.

PMID- 9768611
TI  - Reoperation for recurrent coronary artery disease: results of 200 consecutive
      cases.
AB  - BACKGROUND: It is well known that reoperation for recurrent coronary artery
      disease is more difficult than primary coronary artery bypass grafting. However,
      it is possible to reduce the morbidity and mortality of reoperation to the same
      level as the initial procedure with careful surgical technique. METHODS: A
      retrospective study of the first 200 patients who underwent redo coronary bypass
      grafting was undertaken. RESULTS: In the first 200 cases of redo coronary bypass
      grafting at St George Hospital, Sydney (August 1986-January 1995), there were
      five in-hospital deaths (2.5%). There was one case of sternal infection (0.5%),
      which required surgical debridement, three cases of stroke (1.5%), one case of
      postoperative bleeding (0.5%), which required a return to theatre and six cases
      (3%) required mechanical ventilation for more than 24 h. The need for major
      postoperative support (such as intra-aortic balloon pumping/adrenaline infusion)
      was significantly affected by the degree of urgency and the degree of pre
      operative ventricular impairment. CONCLUSIONS: The mortality rate of redo
      coronary artery bypass grafting in this series is similar to that of primary
      surgery described in other reports.

PMID- 9768612
TI  - Comparative experience of a simple technique for laparoscopic chronic ambulatory
      peritoneal dialysis catheter placement.
AB  - BACKGROUND: Chronic ambulatory peritoneal dialysis (CAPD) is now an established
      technique for renal dialysis. Patients with renal failure cope poorly with major
      surgery and it is vital that the dialysis catheter tip is sited accurately in the
      pelvis if long-term catheter function is to be achieved. Laparoscopic placement
      of CAPD catheters may have potential advantages for renal patients by avoiding
      the morbidity of a laparotomy. METHODS: A retrospective audit was performed of
      all CAPD catheters inserted at the John Hunter Hospital over a 2-year period.
      Results of laparoscopically inserted catheters and those placed at laparotomy
      were compared. RESULTS: Sixty catheters were inserted, 30 laparoscopically and 30
      at laparotomy. The mean operative time was 41 min in the laparoscopic patients
      and 57 min in the laparotomy patients (P = 0.0001). The mean total dose of
      narcotic administered postoperatively was significantly less in the laparoscopic
      group (5 mg vs 65 mg, P = 0.00002). There were three minor peri-operative
      complications in the laparoscopic group and seven peri-operative complications in
      the laparotomy group, three required reoperation and one resulted in the
      patient's death. There were no significant differences in the incidence of exit
      site infection, catheter blockage, peritonitis, and overall catheter survival,
      although the laparoscopically placed catheters had been followed up for a shorter
      period (10 vs 16 months). CONCLUSIONS: This laparoscopic technique is safe and
      effective. Postoperative pain was less than for open placement. Laparoscopically
      placed catheters had a low incidence of peri-operative complications. Medium-term
      patency is similar to conventionally placed catheters. This procedure requires no
      additional equipment to that available for laparoscopic cholecystectomy and takes
      less time than the open operation.

PMID- 9768613
TI  - Tumour cell movement during heating and humidification of insufflating CO2: an in
      vitro model.
AB  - BACKGROUND: Intra-operative hypothermia and port-site recurrence have been
      associated with laparoscopic surgery. Heating and humidification of insufflating
      CO2 may protect against laparoscopy-associated hypothermia. However, the effect
      of heated, humidified CO2 upon tumour cell movement is unknown. METHODS: Twenty
      four in vitro studies that used 4-L plastic bottles were performed. Thirteen
      million human colorectal cancer cells were placed in each bottle. Twelve studies
      used dry room temperature CO2 for insufflation: the remaining 12 used heated,
      humidified CO2 as the insufflating gas. Both groups were subdivided into bottles
      with leaks around the trocars and with airtight sealing around the trocars. Two
      trocars and a laparoscopic grasper were used. The exiting insufflating gas was
      filtered and examined for the presence of cells. Laparoscopic instruments
      agitated the contents of the bottles. The instruments and trocars were washed.
      These washings were examined for the presence of cells. RESULTS: Heated,
      humidified CO2 insufflation was able to maintain a warmer and more humid
      environment within the bottles when compared with dry room-temperature CO2. No
      cells were detected on the gas filters. Tumour cells were found on 12 out of 12
      instruments and 11 out of 12 trocars with dry CO2 insufflation. Tumour cells were
      found on 8 out of 12 instruments and 7 out of 12 trocars with heated humidified
      CO2 insufflation. The only statistically significant difference in tumour cell
      spread to trocars was found between heating and humidification when no leak was
      present, and heating and humidification with leak present, and dry insufflation
      with no leak present (P = 0.015, Fisher's two-tailed exact test). CONCLUSIONS:
      Heating and humidifying CO2 during in vitro laparoscopy does not increase the
      aerosolization of tumour cells when compared with dry CO2. However, the use of
      heated and humidified gas with airtight seals around the trocars in vitro may
      lessen cell deposition on trocars.

PMID- 9768614
TI  - Treatment of large, persistent lymphocoeles using an argon beam coagulator and
      talc.
AB  - BACKGROUND: Lymphocoele formation can be a troublesome surgical complication
      after lymph node dissection and mobilization of large skin flaps. Occasionally,
      lymphocoeles persist for prolonged periods despite repeated aspiration. Treatment
      by sclerotherapy has been recommended, but this requires a prolonged treatment
      time and often causes intense pain. METHODS: The technique used to treat large,
      persistent lymphocoeles involved 'painting' the lymphocoele wall with an argon
      beam coagulator after evacuating its contents. Sterile talc was then distributed
      liberally through the cavity, a closed suction drain placed and the wound closed.
      RESULTS: The procedure was completely successful in each of the four patients
      treated. After a mean follow-up period of 11 months (range 6-15 months) no
      lymphocoele recurrence has occurred. CONCLUSIONS: Use of an argon beam coagulator
      and talc reliably achieves rapid, definitive obliteration of large, persistent
      lymphocoeles.

PMID- 9768615
TI  - A simple method of wound protection for specimen removal in laparoscopic
      colectomy.

PMID- 9768616
TI  - The Murray Clarke Oration: a brief history of burn treatment and the contribution
      of four New Zealand pioneers of plastic surgery.

PMID- 9768617
TI  - Analysis of a large collection of natural HIV-1 integrase sequences, including
      those from long-term nonprogressors.
AB  - A large collection of natural HIV-1 integrase (IN) sequences has not previously
      been described. We reasoned that analysis of such sequences would address whether
      natural variation of HIV-1 IN contributes to the pathogenesis of AIDS and might
      also identify amino acid residues important for IN function. Sequences encoding
      HIV-1 IN were amplified from cryopreserved lymphocytes or plasma obtained at
      different times from 10 hemophilia patients who had been observed for up to 17
      years. The region of the HIV-1 genome that encodes the 288-amino acid IN protein
      was sequenced from a total of 102 clones; information was obtained for 99.97% of
      29,478 amino acid positions. Phylogenetic analysis indicated that patient samples
      were unique. Interpatient nucleic acid distances ranged from 0.8% to 4.9%,
      highlighting the tight conservation of this genomic region. No major differences
      were found between DNA and RNA or between early and late time points from the
      same patient. Significantly, no amino acid changes that might account for the
      variable rate of disease progression between patients were evident. Only one
      amino acid substitution involved a highly conserved residue known to be important
      for enzymatic activity. However, several interesting amino acid substitutions
      were noted, including residues within the C-terminal region of the protein for
      which sequence comparisons between animal retroviruses have not been very
      informative. These results should encourage the pursuit of anti-integrase
      therapies, especially inasmuch as the apparent biologic constraints on the IN
      sequence may deter the development of drug resistance.

PMID- 9768618
TI  - Effective lysis of HIV-1-infected primary CD4+ T cells by a cytotoxic T
      lymphocyte clone directed against a novel A2-restricted reverse-transcriptase
      epitope.
AB  - Most HIV-specific cytotoxic T-lymphocyte (CTL) epitopes have been identified
      using peptide-pulsed and recombinant vaccinia virus-infected targets. These
      systems may not accurately reflect the ability of epitopes to be presented by HIV
      infected T cells. Recent studies suggest, in fact, that some CTL epitopes are
      poorly presented on HIV-infected cells. In this study, we have identified a novel
      A2.1-restricted HIV reverse-transcriptase (RT) epitope and investigated the
      presentation of this epitope by HIV-infected primary CD4+ T cells and T-cell
      lines. A CD8+ CTL clone, isolated from a seropositive subject that recognized a
      novel A2-restricted epitope KYTAFTIPSI (aa 293-302) in RT, was used for these
      studies. Primary CD4+ T cells and the CD4+ T-cell line T1 were infected with
      virus from T1-nPLAP, a cell line stably transfected with HXB-nPLAP, a molecular
      construct of HIV linked to a placental alkaline phosphatase (PLAP) marker gene. A
      uniformly infected cell population, obtained by immunomagnetic selection for PLAP
      expression, was used as targets in CTL assays. HIV-infected T cells were lysed by
      CTL recognizing this RT epitope as effectively as peptide-pulsed targets. This
      suggests that some RT epitopes are good targets for CTL recognition.

PMID- 9768619
TI  - Altered cell-mediated immunity in asymptomatic Colombian natives with positive or
      indeterminate serology for HTLV-I.
AB  - Although HTLV-I infection has been associated with immunosuppression in
      symptomatic patients, no controlled study has been done in asymptomatic carriers.
      We evaluated delayed-type hypersensitivity (DTH) to seven antigens by multitest
      cell-mediated immunity (CMI) in 40 Colombian Indians, 10 HTLV-I-seropositive
      asymptomatic patients, and 30 matched controls. Multitest CMI was placed in the
      forearm and was read 48 hours later by the same physician. A positive reaction
      was defined as > or =2 mm. Hypoergic response was defined as <2 of 7 positive
      reactions per case or control. We found that HTLV-I-seropositive people had fewer
      positive reactions than matched controls (50% versus 64%, respectively; p < .04)
      but no significant difference was found in these populations in the evaluation of
      hypoergic responses. This study suggests the presence in asymptomatic HTLV-I
      positive Colombian Indians of a marginal alteration of cell-mediated immunity
      that cannot be classified as hypoergic.

PMID- 9768620
TI  - Effect of antiretroviral therapy and viral load on the perceived risk of HIV
      transmission and the need for safer sexual practices.
AB  - BACKGROUND: Dramatic reductions in plasma HIV RNA levels are possible with
      current antiretroviral regimens; the effect of potent therapies and
      "undetectable" viral load on the perceived risk of HIV transmission and need for
      safer practices remains unknown. METHODS: A questionnaire was developed to
      examine perceptions of HIV transmission risk and need for safer practices with
      unprotected anal, vaginal, and oral sex and intravenous drug use with needle
      sharing for HIV-discordant couples in which the HIV-infected partner was
      receiving no therapy, was receiving reverse transcriptase inhibitor therapy, and
      protease inhibitor (PI)-based therapy with viral load "undetectable". This was
      applied anonymously to 147 unselected HIV-infected individuals attending a
      university-based HIV clinic. RESULTS: Almost all respondents believed that all
      sexual activities except oral sex were "very risky" and that safer practices were
      "extremely important" for those not receiving antiretroviral agents.
      Significantly fewer considered that anal or vaginal sex was "very risky" for
      those receiving PI therapy (90.9% and 86.0%, respectively), and fewer thought
      that safer practices for anal or vaginal sex were "very important" for those
      receiving PI therapy (93.0% and 91.6%, respectively). In total, 20.4% thought the
      risk of HIV transmission for at least one activity was reduced for those
      receiving PI therapy, and 19.0% believed that the need for safer practices was
      reduced by PI therapy. CONCLUSION: A small but significant proportion of HIV
      infected people perceive the need for safer practices to be reduced during
      antiretroviral therapy, particularly those containing PIs. Even if the risk is
      truly reduced, the importance of safer practices should be conveyed consistently
      and terms such as "undetectable" to describe HIV RNA responses should be avoided.

PMID- 9768621
TI  - Improved outcome of cytomegalovirus retinitis in AIDS patients after introduction
      of protease inhibitors.
AB  - The objective of this study was to evaluate the influence of protease inhibitor
      therapy on the rate of progression and survival of 17 AIDS patients with stable
      Cytomegalovirus retinitis, who were receiving anti-CMV therapy. CD4+ count, HIV
      load, and CMV antigenemia assay were determined at baseline, at the first month,
      and every 3 months thereafter. Median CD4+ count increased from 11 to 87
      cells/mm3, and median HIV RNA level decreased from 4.96 to 3.28 log10 copies/ml,
      after 6 months on therapy. Although 9 patients (53%) relapsed in a median time of
      97 days (range, 15-152 days), no further episodes were observed during a median
      follow-up of 17 months (range, 5-18 months). Thus, the probability of remaining
      free of relapse was twofold higher than that observed in matched patients who did
      not receive protease inhibitors. Median CD4+ count at the 3rd month was higher in
      those individuals who went on to progress (p = .03), and a positive result to a
      CMV antigenemia test was associated with progression of retinitis (relative
      hazard, 4.45; p = .04). Survival rate was 94% at 17 months (89% increase).
      Therefore, protease inhibitor therapy reduces retinitis progression and improves
      survival. However, the immunologic response may not provide initial sufficient
      protection to avoid, or even may play a role on, early CMV progression.

PMID- 9768622
TI  - Phase I study of atevirdine mesylate (U-87201E) monotherapy in HIV-1-infected
      patients.
AB  - The safety, tolerability, and antiviral activity of atevirdine (ATV), a
      nonnucleoside reverse transcriptase inhibitor, were studied in a phase I/II
      clinical trial (ACTG 187) of patients with CD4 counts < or =500/mm3. In all, 34
      HIV-1-infected patients were randomized to receive ATV for 12 weeks in doses
      chosen to achieve one of three serum trough levels: 5 to 13 microM, 14 to 22
      microM, or 23 to 31 microM. Rash was the most common adverse event, with a grade
      3 or 4 rash occurring in 4 patients. No significant change from baseline in HIV-1
      plasma RNA mean copy number was detected at week 4 (+0.09 log10 copies/ml; p =
      .30). However, some evidence indicated moderate antiviral activity at week 4,
      based on median changes in CD4 count (+23/mm3; p = .05), and viral peripheral
      blood mononuclear cell (PBMC) titer (-0.68 log10) copies/ml; p = .03). In
      addition, 2 of 4 patients with detectable baseline serum p24 antigen showed
      declines of >50%. HIV-1 resistance to ATV was detected in 41% of patients and was
      most commonly associated with RT mutations K103N and Y181C. In contrast, the
      Y181C mutation was not detected in ATV-resistant isolates obtained from patients
      enrolled in ACTG 199, a study of ATV given in combination with zidovudine. Under
      the conditions of this study, ATV failed to demonstrate significant
      antiretroviral activity. However, transient in vivo activity might have been
      obscured by rapid development of resistance coupled with inadequate sampling at
      early time points following initiation of ATV therapy.

PMID- 9768623
TI  - Decreased susceptibility of peripheral blood mononuclear cells from individuals
      heterozygous for a mutant CCR5 allele to HIV infection.
AB  - OBJECTIVE: Individuals homozygous for a deletion in the CCR5 gene
      (CCR5delta32/CCR5delta32) are resistant to HIV infection, indicating that this
      particular chemokine receptor plays a crucial role in the initiation of in vivo
      HIV infection. We investigated the effect of the heterozygote genotype
      (CCR5/CCR5delta32) on susceptibility of peripheral blood mononuclear cells (PBMC)
      to HIV infection. DESIGN: Sensitivity to HIV infection of PBMC from volunteers
      with either the CCR5/CCR5, CCR5/CCR5delta32, or CCR5delta32/CCR5delta32 genotypes
      was examined by challenging their PBMCs with serial titers of HIV isolates with
      different cellular tropisms. The genotype of the PBMCs was correlated with the
      lowest viral inoculum required to initiate productive infection with either three
      M-tropic HIV-1 isolates, (92RW009A, HIV-1ada, and HIV-1(59)), one dual-tropic HIV
      1 isolate (92BR021), or two T-tropic HIV-1 isolates (92UG021 and 92UG029).
      RESULTS: PBMCs from the CCR5/CCR5delta32 group required a significantly higher
      inoculum (p value from .036 to .003) to become infected with these three M-tropic
      HIV-1 isolates than did PBMC from the CCR5/CCR5 group, but became infected after
      exposure to an inoculum of T-tropic HIV-1 isolates that was comparable to that
      which infected PBMCs from the CCR5/CCR5 individuals. CONCLUSIONS: The decreased
      susceptibility of PBMCs from individuals heterozygous for the CCR5 deletion to
      HIV infection by M-tropic HIV-1 isolates may provide a mechanistic explanation
      for the delayed progression of disease in some CCR5/CCR5delta32 individuals.

PMID- 9768624
TI  - Resting energy expenditure and body composition in children with HIV infection.
AB  - The purpose of this study was to determine whether alterations in body
      composition, resting energy expenditure (REE), and dietary energy intake are
      associated with growth retardation in HIV-positive children. Body composition
      (deuterium oxide dilution, skinfold measurements), REE (indirect calorimetry),
      and energy intake (24-hour weighed food intake) were evaluated in three groups:
      HIV-positive with growth retardation (HIV+Gr), HIV-positive with normal growth
      (HIV+); and HIV-uninfected with normal growth (HIV-). Children were between 2 and
      11 years of age, afebrile, and free from acute infection. Forty-two children (13
      HIV+Gr, 19 HIV+, 10 HIV-) were studied. Lean body mass was significantly reduced
      in HIV+Gr compared with HIV- (p < .05), and fat mass was significantly reduced in
      HIV+Gr and HIV+ compared with HIV- (p < .05). The percentages of lean and fat
      mass were not significantly different between groups, suggesting that differences
      in lean and fat mass were proportional to differences in body size. Consistent
      with reduced lean body mass, mean REE was significantly lower in HIV+Gr compared
      with HIV- (p < .05). Differences in mean REE/kg of body weight or lean body mass
      between groups were not statistically significant. A significant negative
      correlation was found between REE (kcal/kg/day) and weight-for-age (p = .04), and
      a trend with height-for-age Z-score (p = .07). Mean energy intake was not
      significantly different between groups. This study suggests that lean and fat
      mass are proportionately reduced in HIV-positive children with growth
      retardation. Further studies are necessary to delineate the relationship between
      energy balance and growth in children with HIV infection.

PMID- 9768625
TI  - Trends in HIV prevalence among childbearing women in the United States, 1989
      1994.
AB  - We used data from a national serosurvey to describe national and regional trends
      in the prevalence of HIV among women giving birth in the United States from 1989
      through 1994, and to estimate the number of women between 15 and 44 years old
      with HIV infection who had not yet developed opportunistic infections defining
      AIDS. We compared these estimates with AIDS prevalence and mortality estimates
      from the national AIDS case surveillance system. HIV seroprevalence among
      childbearing women remained stable nationwide from 1989 through 1994, ranging
      from 1.5 to 1.7/1000 women. In the Northeast, seroprevalence declined
      significantly after 1989. Seroprevalence increased significantly in the South
      through 1991 and then stabilized, although seroprevalence among black women
      continued to increase through 1994 in some southern states. Although AIDS
      prevalence and mortality increased nationwide each year from 1989 through 1994,
      the number of women infected with HIV who had not yet developed AIDS changed
      little and was approximately 86,000 in 1994. Our data suggest that new HIV
      infections among women of reproductive age are occurring at a rate that offsets
      losses from this population due to aging, disease progression, and death.

PMID- 9768626
TI  - Nationwide surveillance of HIV-1 prevalence and subtype in young Thai men.
AB  - As part of routine surveillance, an HIV-1 serosurvey of 366,074 members of
      successive cohorts of young Thai men entering service with the Royal Thai Army
      (RTA) was conducted between November 1989 and November 1995. We analyzed regional
      and temporal trends in HIV-1 seroprevalence in young men in Thailand and
      determined the proportion of infections resulting from subtypes E and B in this
      population in 1992 and 1995. The prevalence in 1992 was compared with that in
      1995 by region and demographic group. The HIV-1 subtype was determined in a
      random sample of HIV-1-positive specimens in 1992 and 1995 using a V3 peptide
      enzyme immunoassay. From a peak of 3.7% in 1993, overall seroprevalence declined
      to 3.0% in 1994 and further in 1995 to 2.5%. Between 1992 and 1995, the absolute
      decrease in seroprevalence was greatest in the upper North (from 12.5% to 5.3%),
      where the prevalence has been the highest. Overall, 96.9% and 95.9% of typable
      specimens were determined to be subtype E in 1992 and 1995, respectively. Decline
      in HIV-1 seroprevalence among young men in Thailand has continued, which suggests
      that HIV control programs in Thailand may have been successful in decreasing
      spread of HIV-1. Almost all HIV-1 infections resulted from subtype E.

PMID- 9768627
TI  - Distribution of the CCR5 gene 32-bp deletion in Europe.
AB  - The chemokine receptor CCR5 constitutes the major coreceptor for the macrophage
      tropic strains of HIV-1. A mutant allele of the CCR5 gene called delta32 was
      shown to provide strong resistance to homozygotes against infection by HIV. The
      frequency of the delta32 allele was investigated in 2522 noninfected unrelated
      individuals from 16 different European populations. The delta32 allele was found
      in all populations studied, with a mean frequency of about 9.1%. A north-to-south
      gradient correlating latitude with delta32 allelic frequencies was found (r =
      0.726), with highest allele frequencies in Denmark and Northern France, and the
      lowest allele frequencies in Corsica.

PMID- 9768628
TI  - Continuing high prevalence of HIV and risk behaviors among young men who have sex
      with men: the young men's survey in the San Francisco Bay Area in 1992 to 1993
      and in 1994 to 1995.
AB  - Several recent studies have shown high rates of HIV infection and risk behavior
      among young men who have sex with men (MSM). To assess the direction of the
      epidemic in this population, we replicated a venue-based study performed in the
      San Francisco Bay Area during 1992 and 1993. From May 1994 to September 1995, we
      surveyed 675 MSM aged between 17 and 22. After statistical adjustment for age,
      ethnicity, residence, and site of recruitment, seroprevalence did not change
      significantly between the 1992 to 1993 (8.4%) and the 1994 to 1995 (6.7%)
      surveys. Similarly, no significant changes were found in the rates during the
      previous 6 months of unprotected receptive anal intercourse (23.4% versus 24.9%),
      injection drug use (8.0% versus 7.8%), or needle sharing among injection drug
      users (56.3% versus 64.5%) between the two surveys. Despite the increased
      attention that the problem of high risk behavior among young MSM has received,
      effective prevention interventions for MSM are needed as profoundly now as they
      had been several years ago.

PMID- 9768629
TI  - Pneumocystis carinii pneumonia incidence and chemoprophylaxis failure in
      ambulatory HIV-infected patients. HIV Outpatient Study (HOPS) Investigators.
AB  - BACKGROUND: Pneumocystis carinii pneumonia (PCP) remains the most frequently
      reported serious opportunistic infection in AIDS patients and the second highest
      cause of mortality among persons with AIDS in the United States, despite the
      availability of effective chemoprophylaxis. METHODS: To evaluate incidence of PCP
      and determinants of PCP chemoprophylaxis failure, we analyzed data from 2842
      patients visits to infectious diseases physicians at 10 HIV clinics (eight
      private and two public) in eight U.S. cities from January 1992 through June 1996
      as part of the HIV Outpatient Study (HOPS). We performed a time-dependent
      regression analysis to examine potential determinants of PCP chemoprophylaxis
      failure. RESULTS: The incidence of chemoprophylaxis failure was 4.6 PCP cases/100
      person-years on chemoprophylaxis; these cases represent 67% of all incident
      episodes of PCP. In a multivariate analysis, the only significant predictors of
      chemoprophylaxis failure were the use of agents other than trimethoprim
      sulfamethoxazole (TMP-SMX), history of prior PCP, and a CD4+ T-lymphocyte cell
      count of <50 cells/microl. Dosing or frequency of TMP-SMX did not seem to
      influence risk of chemoprophylaxis failure. DISCUSSION: Chemoprophylaxis failure,
      especially among those with the most advanced immunosuppression or history of
      prior PCP, was the most significant source of new PCP cases in the HOPS cohort
      and thus represents one of the largest contributors to morbidity and mortality in
      this cohort.

PMID- 9768630
TI  - Infant feeding and risk of mother-to-child transmission of HIV-1 in Sao Paulo
      State, Brazil. Sao Paulo Collaborative Study for Vertical Transmission of HIV-1.
AB  - Although vertical transmission of HIV-1 can occur through breast-feeding, little
      is known about the effect of colostrum, duration of breast-feeding, mixing
      feeding, and nipple pathology. We used retrospective cohort data to examine the
      association between breast-feeding-related factors and transmission of HIV-1 from
      mother to child in Sao Paulo State, Brazil. Information on maternal and postnatal
      factors was collected by medical record review and interview. Infection status
      was determined for 434 children by anti-HIV-1 tests performed beyond 18 months of
      age or diagnosis of AIDS at any age. Among 168 breast-fed children, the risk of
      transmission of HIV-1 was 21%, compared with 13% (p = .01) among 264 children
      artificially fed. Breast-feeding was independently and significantly associated
      with mother-to-child transmission of HIV-1 after controlling for stage of
      maternal HIV-1 disease (odds ratio [OR] = 2.2; 95% confidence interval [CI], 1.3
      3.8). A trend was shown toward an increased risk of transmission with longer
      duration of breast-feeding, a history of bleeding nipples, and introduction of
      other liquid food before weaning, but these associations were not statistically
      significant. History of colostrum intake or cracked nipples without bleeding were
      not associated with transmission. Most of the women who breast-fed were unaware
      of their HIV-1 infection status at the time of delivery. Avoidance of mixed
      feeding and withholding of breast-feeding in the presence of bleeding nipples
      should be considered in further research as strategies to reduce postnatal
      transmission of HIV-1 in settings in which safe and sustainable alternatives for
      breast-feeding are not yet available.

PMID- 9768631
TI  - Selecting the optimum dose for a new soft gelatin capsule formulation of
      saquinavir. NV15107 Study Group.

PMID- 9768632
TI  - Cotton-wool spots in primary HIV infection.

PMID- 9768633
TI  - Rapid progression of HIV infection in HBeAg-positive patients.

PMID- 9768634
TI  - HIV prevalence among injection drug users in three Northern California
      communities.

PMID- 9768635
TI  - Autoimmune thyroid disease genes come in many styles and colors.

PMID- 9768636
TI  - Linkage disequilibrium between the human leukocyte antigen class II region of the
      major histocompatibility complex and Graves' disease: replication using a
      population case control and family-based study.
AB  - Early case control studies found association of the DRB1 allele, DR3, with
      Graves' disease (GD). Recent reports, claim the DQA1 allele, DQA1*0501, to be the
      primary susceptibility determinant within the human leukocyte antigen (HLA) class
      II region. We typed 228 GD patients, 364 controls, and 98 families (parents, GD,
      and unaffected sibling) at the DRB1, DQB1, and DQA1 loci. The case control study
      showed an increased frequency in GD, compared to controls, of DRB1*0304 (47% vs.
      24%; pc < 1.4 x 10(-5)), DQB1*02 (58% vs. 46%; pc < 0.035), DQB1*0301/4 (42% vs.
      28%; pc < 3.5 x 10(-3)) and DQA1*0501 (67%, vs. 39%; pc < 7 x 10(-6)). The
      DRB1*0304-DQB1*02-DQA1*0501 haplotype was increased in GD (47%) vs. controls
      (24%; pc < 1.8 x 10(-5); odds ratio = 2.72). No independent association of these
      alleles was observed. Preferential transmission of DRB1*0304-DQB1*02-DQA1*0501
      from parents heterozygous for the haplotype to GD siblings (72%) was seen in the
      families (chi2 = 11.95; 1 d.f.; P = 0.0005). Lack of preferential transmission to
      unaffected siblings (53%; chi2 = 0.19; 1 d.f.; P = NS) excluded segregation
      distortion. These results show that linkage disequilibrium between GD and the HLA
      class II region is due to the extended haplotype DRB1*0304-DQB1*02-DQA1*0501.

PMID- 9768637
TI  - What's happening to our iodine?

PMID- 9768638
TI  - Iodine nutrition in the United States. Trends and public health implications:
      iodine excretion data from National Health and Nutrition Examination Surveys I
      and III (1971-1974 and 1988-1994)
AB  - Iodine deficiency in a population causes increased prevalence of goiter and, more
      importantly, may increase the risk for intellectual deficiency in that
      population. The National Health and Nutrition Examination Surveys [NHANES I (1971
      1974) and (NHANES III (1988-1994)] measured urinary iodine (UI) concentrations.
      UI concentrations are an indicator of the adequacy of iodine intake for a
      population. The median UI concentrations in iodine-sufficient populations should
      be greater than 10 microg/dL, and no more than 20% of the population should have
      UI concentrations less than 5 microg/dL. Median UI concentrations from both
      NHANES I and NHANES III indicate adequate iodine intake for the overall U.S.
      population, but the median concentration decreased more than 50% between 1971
      1974 (32.0+/-0.6 microg/dL) and 1988-1994 (14.5+/-0.3 microg/dL). Low UI
      concentrations (<5 microg/dL) were found in 11.7% of the 1988-1994 population, a
      4.5-fold increase over the proportion in the 1971-1974 population. The percentage
      of people excreting low concentrations of iodine (UI, <5 microg/dL) increased in
      all age groups. In pregnant women, 6.7%, and in women of child-bearing age, 14.9%
      had UI concentrations below 5 microg/dL. The findings in 1988-1994, although not
      indicative of iodine deficiency in the overall U.S. population, define a trend
      that must be monitored.

PMID- 9768639
TI  - Tight control of growth hormone: an attainable outcome for acromegaly treatment.

PMID- 9768640
TI  - Transsphenoidal microsurgery for growth hormone-secreting pituitary adenomas:
      initial outcome and long-term results.
AB  - Treatment of acromegaly has long been recognized as necessary to relieve
      symptoms, halt progression of deformities, and decompress the sella turcica. More
      recently, treatment strategies have focused on decreasing GH levels to a point at
      which mortality rates normalize, thereby redefining previous concepts of a cure.
      No surgical series to date has investigated the long-term effect of treatment on
      mortality rates. We retrospectively reviewed 254 consecutive patients with
      acromegaly who underwent transsphenoidal microsurgery of GH-secreting adenomas
      between 1974-1992. Seventy-six percent of these patients had basal GH levels <5
      ng/mL within 30 days of surgery, and 24% had persistent disease. Multivariate
      analysis revealed that higher stage, grade, and preoperative GH levels were all
      predictive of persistence (P < 0.01). Long-term follow-up was obtained on 129 of
      the patients in initial remission. Of these, 9 (7%) had disease recurrence and
      120 remained in remission. The incidence of major postoperative complications was
      8% (2% permanent diabetes insipidus, 2% cerebrospinal fluid leaks requiring
      surgery, 2% meningitis, and 2% hypopituitarism), with no mortality. In contrast
      to the 2.4- to 4.8-fold increased mortality among untreated acromegalics, the
      mortality rate among patients with posttherapy GH levels <5 ng/mL was equivalent
      to that of age- and sex-matched controls. Aggressive therapy to normalize GH
      levels should therefore be instituted at diagnosis.

PMID- 9768641
TI  - Long-term mortality after transsphenoidal surgery and adjunctive therapy for
      acromegaly.
AB  - To analyze the long term outcome after multimodality therapy for acromegaly, a
      retrospective review was performed on 162 patients who underwent transsphenoidal
      surgery at Massachusetts General Hospital between 1978 and 1996. The surgical
      cure rate for microadenomas was 91%, that for macroadenomas was 48%, and it was
      57% overall. The surgical cure rate was significantly dependent on tumor size,
      but was not dependent on age or sex. An improvement in the surgical cure rate was
      noted over the course of the review, from 45% before 1987 to 73% since 1991. Long
      term follow-up was obtained in 99% of U.S. residents (149 of 151), with a mean
      follow-up period of 7.8 yr. Adjuvant radiation and/or pharmacological therapy was
      given to 61 patients. Of the entire group, 83% (124 of 149) were in biochemical
      remission as determined by normalization of serum insulin-like growth factor I
      levels or by GH suppression after oral glucose tolerance testing at last contact
      or at death. The recurrence rate was 6% at 10 yr and 10% at 15 yr after surgery
      in those patients who initially met the criteria for surgical cure. The 10-yr
      survival rate was 88%, and there were 12 deaths at postoperative intervals of 2
      12 yr, with the most common cause of death being cardiovascular disease. A Cox
      proportional hazards model showed that patient-years with persistent disease
      carried a 3.5-fold [95% confidence interval (CI), 1.0-12; P = 0.02] relative
      mortality risk compared to those patient-years in remission. A Poisson person
      years regression analysis showed no significant difference in survival between
      those 86 patients cured at operation and an age- and sex-matched sample from the
      U.S. population [standardized mortality ratio (SMR), 0.84; 95% CI, 0.3-2.2; P =
      0.35]. A similar analysis on the entire group of 149 patients showed no
      significant difference in survival from that in a control sample (SMR, 1.16; 95%
      CI, 0.66-2.0; P = 0.3). Mortality risk for patient-years with persistent active
      disease after unsuccessful treatment vs. that in the U.S. population sample
      remained increased (SMR, 1.8; 95% CI, 0.9-3.6; P = .05). This analysis suggests
      that the decreased survival previously reported to be associated with acromegaly
      can be normalized by successful surgical and adjunctive therapy.

PMID- 9768642
TI  - Profiles of the Endocrine Clinic: the Mayo Clinic.
AB  - It is evident that clinical endocrinology, as a discipline, is entering a
      particularly exciting period in its evolution. Knowledge gained from basic and
      clinical research is being translated at the bedside for the benefit of our
      patients. The emergence of new drugs and novel treatment strategies has equipped
      clinical endocrinologists with the tools to more successfully combat many old
      enemies, such as diabetes and osteoporosis. Realization of full benefit from
      these exciting new tools requires a practice model in which the clinical
      endocrinologist's role is preeminent and is coordinated and integrated with those
      of practitioners drawn from other disciplines. The Mayo Division of
      Endocrinology, Metabolism, and Nutrition provides one such model of highly
      integrated care. We believe that as the pace of knowledge regarding basic
      mechanisms of disease and their treatment quickens, such integrated divisions
      will prove well suited to deliver the highest quality care to people with
      endocrine disorders.

PMID- 9768643
TI  - Issues in testosterone replacement in older men.

PMID- 9768644
TI  - A spontaneous and severe hyperstimulation of the ovaries revealing a gonadotroph
      adenoma.
AB  - We report an unusual case of a gonadotroph adenoma in a 34-yr-old woman, revealed
      by a dramatic rise in the plasma estradiol (E2) concentration (26,800 pmol/L;
      normal, <370), with nonsuppressed FSH and LH levels (4.9 and 2.4 mIU/mL,
      respectively). The PRL level was 503 ng/mL. The testosterone and progesterone
      levels were 7 and 17 nmol/L, respectively. The levels of inhibin alpha, inhibin
      A, and inhibin B were increased compared to normal values in both the follicular
      (fp) and luteal (lp) phases of the menstrual cycle [inhibin alpha, 1986 IU/L (fp
      normal, <700; lp normal, <1650); inhibin A, 254 pg/mL (fp normal, <20; lp normal,
      <120); inhibin B, 246 pg/mL (fp normal, <150; lp normal, <30 lp)]. Pituitary
      magnetic resonance imaging revealed a huge pituitary adenoma. After
      transphenoidal surgery, the patient presented with pituitary insufficiency and
      diabetes insipidus. RT-PCR of the tumor tissue was positive for LHbeta, FSHbeta,
      alpha-subunit, and PRL. This case is of particular interest because 1) although
      the E2 level was extremely high, the patient did not present with ascitis,
      suggesting that chronic elevated E2 does not play a crucial role in the
      hyperstimulation symptoms; 2) the extreme rise in E2 was related to the
      cosecretion of FSH and LH, confirming the two-cell two-gonadotropin theory; and
      3) the rise in inhibin B is associated with FSH secretion, whereas the rise in
      inhibin A is probably due to luteinization.

PMID- 9768645
TI  - An unusual pituitary pathology.

PMID- 9768646
TI  - A PHEX gene mutation is responsible for adult-onset vitamin D-resistant
      hypophosphatemic osteomalacia: evidence that the disorder is not a distinct
      entity from X-linked hypophosphatemic rickets.
AB  - Previous investigators described a kindred with an X-linked dominant form of
      phosphate wasting in which affected children did not have radiographic evidence
      of rickets, whereas older individuals were progressively disabled by severe
      bowing. They proposed that this kindred suffered from a distinct disorder that
      they referred to as adult-onset vitamin D-resistant hypophosphatemic osteomalacia
      (AVDRR). We recently identified a gene, PHEX, that is responsible for the
      disorder X-linked hypophosphatemic rickets. To determine whether AVDRR is a
      distinct form of phosphate wasting, we searched for PHEX mutations in affected
      members of the original AVDRR kindred. We found that affected individuals have a
      missense mutation in PHEX exon 16 that results in an amino acid change from
      leucine to proline in residue 555. Clinical evaluation of individuals from this
      family indicates that some of these individuals display classic features of X
      linked hypophosphatemic rickets, and we were unable to verify progressive bowing
      in adults. In light of the variability in the clinical spectrum of X-linked
      hypophosphatemic rickets and the presence of a PHEX mutation in affected members
      of this kindred, we conclude that there is only one form of X-linked dominant
      phosphate wasting.

PMID- 9768647
TI  - Peak bone mass in young healthy men is correlated with the magnitude of
      endogenous growth hormone secretion.
AB  - GH plays a key role during adolescence in longitudinal bone growth and the
      attainment of peak bone mass. We explored the hypothesis that in early adulthood,
      bone mineral accretion and/or maintenance in men with normal GH and bone mineral
      status are related to the magnitude of endogenous GH secretion. Overnight plasma
      GH concentrations (sampled every 10 min from 2100-0500 h) were measured in 15
      healthy, lean, Caucasian men (age, 24+/-1 yr; body mass index, 22.6+/-0.6 kg/m2;
      mean +/- SE). Total body, femur, and lumbar spine bone mineral mass/density were
      measured by dual energy x-ray absorptiometry. Total body and femoral bone mineral
      mass correlated with both total nocturnal GH and maximal GH concentrations even
      when bone mineral mass was adjusted by height (P = 0.005-0.02; r = 0.58-0.74).
      Neither spinal nor total body bone mineral density (BMD) correlated with GH.
      Maximum GH correlated with the BMD of all four femoral sites (P = 0.01-0.04; r =
      0.55-0.66), whereas total nocturnal GH correlated with only one (trochanter; P =
      0.01; r = 0.64) femoral site. Our data support the hypothesis that GH continues
      to play a role in the accretion and/or maintenance of bone mass in young men.
      This relationship is more evident in the bone mineral mass achieved than in the
      BMD.

PMID- 9768648
TI  - Effect of obesity on estradiol level, and its relationship to leptin, bone
      maturation, and bone mineral density in children.
AB  - The purpose of this study was to investigate 24-h estradiol and leptin levels in
      obese and nonobese children to further understand the roles of estradiol and
      leptin in obesity and puberty. We measured serum estradiol, leptin, insulin,
      glucose, and GH levels every hour for 24 h in 18 obese (12 females and 6 males)
      and 30 nonobese (11 females and 19 males) prepubertal and early pubertal (stages
      1-2) children. Bone age and dual energy x-ray absortiometry (DEXA) were obtained
      upon completion of the 24-h study. Obese children were significantly younger than
      nonobese children, with no difference in pubertal stage, height, or bone age
      between the 2 groups. Obese children had greater bone age to chronological age
      ratios than nonobese children, indicating a more advanced rate of bone
      maturation. Mean 24-h estradiol levels correlated significantly with
      chronological age and bone age as well as with insulin-like growth factor I,
      insulin-like growth factor-binding protein-3, dehydroepiandrosterone sulfate,
      mean 24-h GH, and lean body mass. Mean 24-h estradiol levels did not differ
      between obese and nonobese children [1.65+/-1.47 us. 2.75+/-3.30 pmol/L (0.45+/
      0.40 vs. 0.75+/-0.90 pg/mL), respectively]. Similar mean 24-h estradiol levels in
      obese and nonobese children are consistent with the increased bone maturation of
      the obese children. Estradiol did not correlate significantly with DEXA fat mass,
      body mass index, or arm fat measures of adiposity. Obese children had higher 24-h
      mean leptin concentrations than nonobese children (28.6+/-17.4 vs. 6.8+/-7.1
      ng/mL; P < 0.001). Leptin concentrations positively correlated with DEXA fat
      mass, body mass index, and arm fat measurement of adiposity. Girls had higher 24
      h mean leptin levels than boys when controlling for adiposity. Estradiol and
      leptin concentrations fluctuated over a 24-h period in both groups, with all
      children having higher leptin concentrations at night and higher estradiol
      concentrations in the morning. This diurnal rhythm was of a similar pattern, but
      at higher levels for leptin and lower levels for estradiol in the obese children
      compared to nonobese children. There was no significant correlation between
      estradiol and leptin levels. Bone mineral density, as measured by DEXA, did not
      differ between obese and nonobese children. Similar bone mineral density values
      in obese and nonobese children are consistent with the increased bone maturation
      of the obese children. Bone mineral density was not correlated with estradiol or
      leptin level in these children. In conclusion, obese children had similar
      estradiol levels and equivalent bone ages at a younger chronological age than
      nonobese children. Leptin was higher in these obese children, but did not
      correlate with estradiol level or bone age. These findings suggest that the role
      of leptin in both obesity and pubertal development is not directly correlated
      with the estradiol level.

PMID- 9768649
TI  - Effect of growth hormone (GH) on serum concentrations of leptin: study in
      patients with acromegaly and GH deficiency.
AB  - As leptin, an ob gene product, plays a pivotal role in the regulation of
      adiposity and energy homeostasis, the level of its expression is likely to
      fluctuate under various physiological, nutritional, and disease conditions.
      Reports regarding the effect of GH on serum leptin levels are inconsistent. We
      have measured serum leptin levels and correlated them with several variables in
      patients with acromegaly, patients with adult GH deficiency (GHD), and normal
      controls. In 116 normal subjects, the mean serum concentration of leptin was
      5.0+/-2.8 (mean +/- SD) ng/mL in men (n = 42) and 10.7+/-7.3 ng/mL in women (n =
      73), respectively. As reported previously, the leptin levels in women were
      significantly (P < 0.001) higher than in men, and there was a strong positive
      correlation between log-transformed serum leptin levels and percent body fat in
      simple regression analysis (in men: r = 0.606; P < 0.0001; in women: r = 0.707; P
      < 0.0001). In 36 acromegalic patients, the percent body fat mass was
      significantly lower than that in normal subjects, and the mean serum leptin level
      was 2.2+/-1.8 ng/mL in men (n = 18) and 3.6+/-2.5 ng/mL in women (n = 18).
      Analysis of covariance revealed that serum leptin levels in acromegalics were
      significantly lower than those in normal subjects after correcting percent body
      fat (P = 0.016 for men and P < 0001 for women). In male patients with GHD (n =
      20), the mean percent body fat was significantly (P < 0.05) higher than that in
      age-matched controls, whereas the value in female GHD patients (n = 15) did not
      differ from that in age-matched controls. Serum leptin levels in GHD patients
      were 5.1+/-2.5 ng/mL in men and 11.5+/-8.1 ng/mL in women, which were not
      different from those in normal subjects adjusted for percent body fat mass. In
      multiple regression analysis models with log-transformed leptin as the dependent
      variable, gender, percent body fat (or body fat mass), and serum insulin-like
      growth factor I levels entered the equations at a statistically significant
      level. These data suggest that excess GH/insulin-like growth factor I reduces
      serum leptin levels by reducing body fat mass and/or by unknown mechanisms.

PMID- 9768650
TI  - A randomized, cross-over trial of once-daily versus twice-daily parathyroid
      hormone 1-34 in treatment of hypoparathyroidism.
AB  - Once-daily sc injection of PTH 1-34 can normalize mean serum and urine calcium
      levels in patients with hypoparathyroidism; however, once-daily PTH has
      diminishing effects on serum calcium after 12 h, such that serum calcium levels
      fall below the normal range in some patients. Once-daily PTH also causes a marked
      increase in bone turnover, with persistent increases in markers of bone formation
      and resorption. To test the hypothesis that a twice-daily PTH regimen can produce
      more physiological control than a once-daily regimen, we performed a randomized
      cross-over trial, lasting 28 weeks, in 17 adult subjects with hypoparathyroidism.
      Each 14-week study arm was divided into a 2-week inpatient dose-adjustment phase
      and a 12-week outpatient phase. The PTH dose (given sc once daily at 0900 h or
      twice daily with one dose at 0900 h and the other at 2100 h) was adjusted to
      maintain both serum and urine calcium within, or close to, the normal range.
      During the second half of the day (12-24 h), twice-daily PTH increased serum
      calcium and magnesium levels more effectively than once-daily PTH. In patients
      with calcium receptor mutations (CaR), once-daily PTH normalized urine calcium,
      provided that serum calcium was maintained at levels below normal range. However,
      twice-daily PTH treatment produced higher mean serum calcium in patients with CaR
      with no significant rise in urine calcium excretion, and with no significant
      differences in either serum or urine calcium levels between CaR and patients with
      acquired or idiopathic hypoparathyroidism. Thus, treatment with twice-daily PTH
      is the better regimen for patients with CaR to overcome their tendency to
      hypercalciuria while producing near-normal levels of serum calcium. The total
      daily PTH dose was markedly reduced with the twice-daily regimen (twice daily
      46+/-52 vs. once daily 97+/-60 microg/day, P < 0.001). We conclude that a twice
      daily PTH regimen provides effective treatment of hypoparathyroidism and reduces
      the variation in serum calcium levels at a lower total daily PTH dose.

PMID- 9768651
TI  - A prospective study on cortisol, dehydroepiandrosterone sulfate, and cognitive
      function in the elderly.
AB  - The objective of this study was to investigate the relation between the
      peripheral concentrations of the adrenal steroid hormones cortisol and
      dehydroepiandrosterone sulfate (DHEAS) and cognitive impairment and decline. A
      prospective study design was used. The setting was a suburb of Rotterdam, The
      Netherlands. The study population consisted of a sample of 189 healthy
      participants from the population-based Rotterdam Study, aged 55-80 yr, who were
      invited for an additional examination. Follow-up examinations took place 1.9 yr
      after baseline, on the average. We determined fasting blood levels of DHEAS
      before dexamethasone administration and of cortisol and corticosteroid-binding
      globulin before and after the administration of 1 mg dexamethasone overnight. The
      30-point Mini-Mental State Examination (MMSE) was used to assess cognition. The
      associations with cognitive impairment (MMSE score of <26; 6% of the sample) and
      cognitive decline (drop in MMSE score of >1 point/yr; 24%) were estimated using
      logistic regression, with adjustment for age, sex, education, and depressive
      symptoms. An increase of 1 SD in the estimate of free cortisol (SD = 30.3) was
      associated with cognitive impairment, although not significantly [odds ratio (OR)
      = 1.5; 95% confidence interval (CI), 0.9-2.4]. A 1 SD increase in the natural
      logarithm of cortisol after the administration of 1 mg dexamethasone (SD = 0.68)
      was associated with an OR for cognitive decline of 1.5 (95% CI, 1.0-2.3). A 1 SD
      increase in DHEAS (SD = 2.10 micromol/L) was inversely, but nonsignificantly,
      related to cognitive impairment (OR = 0.5; 95% CI, 0.2-1.1) and cognitive decline
      (OR = 0.6; 95% CI, 0.4-1.1). The ratio of free cortisol over DHEAS was
      significantly related to cognitive impairment (OR = 1.8; 95% CI, 1.0-3.2). This
      prospective study among healthy elderly subjects suggested that basal free
      cortisol levels were positively related to cognitive impairment, and cortisol
      levels after dexamethasone treatment were related to cognitive decline. There was
      an inverse, but nonsignificant, association between DHEAS and cognitive
      impairment and decline.

PMID- 9768652
TI  - Changes in thyroid hormone levels during growth hormone therapy in initially
      euthyroid patients: lack of need for thyroxine supplementation.
AB  - The occurrence of central hypothyroidism in previously euthyroid children during
      GH therapy has been reported with widely varying incidence. We monitored the
      acute effects on the hypothalamic-pituitary-thyroid axis in 15 euthyroid children
      with classic GH deficiency during the first year of GH therapy. All were
      initially euthyroid, as assessed by normal baseline TSH, T4, free T4, and T3
      levels and negative antithyroid antibodies. A thyroid profile (T4, free T4 index,
      T3, rT3, and TSH) was performed at baseline and 1, 3, 6, 9, and 12-15 months
      after GH therapy began; a TRH stimulation test was performed at baseline and
      after 1, 3, and 9 months of therapy. By 1 month, there were significant decreases
      in T4, free T4 index, and rT3, and significant increases in T3 and the T3/T4
      ratio. The changes from baseline values were greatest at 1 month, were almost
      universal for all thyroid values, and showed a gradual return to baseline from 3
      12 months. There were no clinical signs of hypothyroidism and no change in
      baseline or TRH-stimulated TSH levels or in cholesterol levels, and all patients
      grew at velocities expected for the treatment schedule. There is little evidence
      for the development of clinically significant hypothyroidism in the great
      majority of initially euthyroid patients after GH therapy is begun. T4
      supplementation is seldom needed in such patients.

PMID- 9768653
TI  - Can weight gain in healthy, nonobese volunteers be predicted by differences in
      baseline plasma insulin concentration?
AB  - In this study, we have evaluated the effect, over approximately 14 yr, of
      differences in baseline degree of hyperinsulinemia on weight gain in 647 healthy,
      nonobese factory workers. The subjects were divided into 4 quartiles, on the
      basis of their plasma insulin response to an oral glucose challenge, in 1981. At
      that time, the mean (+/-SD) plasma insulin concentration, 2 h after the glucose
      challenge, varied from 18+/-5 to 106+/-42 microU/mL. Despite this approximate 6
      fold difference in plasma insulin response at baseline, the weight gain over the
      period of observation was similar in all quartiles, with mean (+/-SD) increments
      (kg) of 1.8+/-5.1, 1.6+/-5.3, 2.3+/-5.2, and 2.3+/-5.7, going from the lowest
      quartile to the highest quartile, in terms of insulin concentration. Furthermore,
      when the population was considered as a whole, there was no correlation between
      baseline degree of hyperinsulinemia and change in either absolute (r = 0.004) or
      percent (r = 0.003) weight gain. Finally, there was no difference in the number
      of individuals who gained more than 4.5 kg, as a function of their baseline
      insulin response. Consequently, we conclude that 6-fold differences in plasma
      insulin responses to glucose do not predict weight gain in a healthy, nonobese
      population.

PMID- 9768654
TI  - In pubertal girls, naloxone fails to reverse the suppression of luteinizing
      hormone secretion by estradiol.
AB  - Estradiol (E2) negative feedback on LH secretion was examined in 10 pubertal
      girls, testing the hypothesis that E2 suppresses LH pulse frequency and amplitude
      through opioid pathways. At 1000 h, a 32-h saline infusion was given, followed 1
      week later by an E2 infusion at 13.8 nmol/m2 x h. During both infusions, four iv
      boluses of saline were given hourly beginning at 1200 h, and four naloxone iv
      boluses (0.1 mg/kg each) were given hourly beginning at 1200 h on the following
      day. Blood was obtained every 15 min for LH determination and every 60 min for E2
      determination from 1200 h to the end of the infusion. E2 infusion increased the
      mean serum E2 concentration from 44+/-17 to 112+/-26 pmol/L (P < 0.01). The mean
      LH concentration between 2200-1200 h decreased from 3.19+/-0.89 to 1.99+/-0.65
      IU/L (P = 0.014), and LH pulse amplitude decreased from 3.4+/-0.6 to 2.6+/-0.5
      IU/L (P = 0.0076). Although there were 1.2 fewer pulses during E2 infusion
      compared to saline infusion, differences did not reach significance (P = 0.1; 95%
      confidence interval for the difference, -3.5, 1.1). Pituitary responsiveness to
      GnRH, assessed at the end of the infusion by administering 250 ng/kg GnRH iv, did
      not change during E2 infusion. The effect of naloxone blockade of opioid activity
      on LH secretion was determined by assessing the area under the curve (AUC) from
      1200-1600 h. During saline infusion, the LH AUC was 1122+/-375 IU/L during saline
      boluses and 1575+/-403 IU/L during naloxone boluses (P = 0.39). When E2 was
      infused, the LH AUCs during saline and naloxone boluses were 865+/-249 and 866+/
      250 IU/L, respectively. Thus, in pubertal girls: 1) E2 decreases the LH
      concentration and LH pulse amplitude; 2) the main site of negative feedback
      effect of E2 appears to be at the level of the hypothalamus; 3) an increase in LH
      secretion after naloxone administration could not be demonstrated in these girls
      and may depend on the maturity of the hypothalamic-pituitary-gonadal axis; and 4)
      opioid receptor blockade does not reverse the E2 inhibition of LH secretion even
      in the most mature girls. Thus, E2 suppression of LH secretion in pubertal girls
      appears to be mediated by a decrease in hypothalamic GnRH secretion that is
      independent of opioid pathways.

PMID- 9768655
TI  - Levels of adrenocortical autoantibodies correlate with the degree of adrenal
      dysfunction in subjects with preclinical Addison's disease.
AB  - To test the hypothesis that levels of adrenal autoantibodies correlate with the
      degree of adrenal dysfunction, we followed up adrenal cortex autoantibody (ACA)
      titers and 21-hydroxylase (21OH) autoantibody (21OHAb) levels in 19 ACA-positive
      subjects with preclinical Addison's disease. On enrollment, all the 19 ACA
      positive subjects were positive for 21OHAb. At follow-up, the concordance rate
      for simultaneous presence/absence of both ACA and 21OHAb was as high as 91% and a
      strong, positive correlation between 21OHAb levels and ACA titers was observed (P
      < 0.0001). The levels of adrenal autoantibodies were positively associated with
      the severity of adrenal dysfunction (ANOVA, P < 0.0001 for both 21OHAb and ACA):
      the 21OH index was significantly lower at stage 0 or 1 than at stage 2+3
      (corrected P < 0.001 andP < 0.05) or stage 4 (corrected P < 0.001 and <0.01).
      Similarly, ACA titer at stage 4 was significantly higher than stage 0 (P <
      0.001), stage 1 (P < 0.001), and stage 2+3 (P < 0.05); and ACA titer at stage 2+3
      was higher than stage 0 (P < 0.001) and stage 1 (P < 0.05). In subjects with
      progression of adrenal dysfunction (n = 14), levels of 21OHAb and ACA increased
      significantly (P = 0.041 and P = 0.002) during the follow-up period. In 5
      subjects, the remission of biochemical signs of adrenal dysfunction was
      associated with the disappearance of both ACA and 21OHAb. Our study shows that
      the levels of adrenal autoantibodies correlate with the degree of adrenal
      dysfunction, and this suggests that production of high-level 21OHAb strongly
      signals the destructive phase of the autoimmune disease process.

PMID- 9768656
TI  - Human growth hormone treatment of short-stature children born small for
      gestational age: effect on muscle and adipose tissue mass during a 3-year
      treatment period and after 1 year's withdrawal.
AB  - In addition to its growth promoting effect, GH has profound metabolic effects
      that have not always been evaluated in longitudinal studies. We have recently
      shown that the effect of GH on body composition can be evaluated by magnetic
      resonance imaging measurement of adipose and muscle tissue cross-sectional (cs)
      areas in the thigh. The aim of this study was to evaluate the long-term effects
      of human GH (hGH) (0.2 IU/kg day) on muscle and adipose tissue mass during a 3-yr
      treatment period and after 1 year's withdrawal in short SGA (small for
      gestational age) children. Measurement of muscle and fat tissue mass by magnetic
      resonance imaging of the thighs was used to study the metabolic effect of hGH in
      14 prepubertal short children born SGA. Results were compared with those of a
      control group of 7 normal children followed longitudinally. An increase of muscle
      tissue cs area was observed during the 3 yr of hGH treatment, an increase which
      was significantly different during the first 2 yr of treatment from that seen in
      controls (+31.2+/-2.6% and +18.1+/-1.8% during the 1st and 2nd year,
      respectively, vs. +9.1+/-2.6% change during 1 yr in controls). After a
      significant decrease in adipose tissue cs area during the first year of therapy (
      16.4+/-3.4% vs. baseline values), an increase in adipose tissue cs area occurred
      during the second and third years. At the end of the third year, the muscle
      tissue cs area change was significantly greater in SGA-treated children, as
      compared with controls (+71.6+/-4.6% vs. 22.1+/-4.6%; P < 0.001), whereas the
      adipose tissue cs area change was similar in the two groups (+12.6+/-9.5% vs.
      +19.9+/-4.2%). After hGH withdrawal, the effects were opposite after 3 months, as
      compared with those observed after the first 3 months of hGH administration,
      whereas no additional significant change was seen after 1 yr off treatment,
      indicating the maintenance of muscle and adipose tissue mass. In conclusion, hGH
      administered to SGA children is effective in improving growth velocity and has
      long-term effects on muscle and adipose tissue mass. These effects may lead to
      speculation about the sensitivity of these tissues to GH. The physiological
      consequences of such effects must be evaluated.

PMID- 9768657
TI  - Rapid cardiovascular action of aldosterone in man.
AB  - Rapid nongenomic in vitro effects of aldosterone have been demonstrated recently
      in cultured vascular smooth muscle and endothelial cells. But there is, as yet,
      little evidence for corresponding in vivo effects. The present study thus
      investigates the rapid nongenomic effects of aldosterone on human cardiovascular
      function. In a double-blind placebo-controlled randomized parallel trial on 17
      patients with suspected coronary heart disease, the effect of 1 mg aldosterone iv
      on cardiovascular function was assessed during cardiac catheterization.
      Hemodynamic parameters (such as heart rate, left ventricular and atrial
      pressures, arterial pressures, vascular resistances, and cardiac output) were
      measured before and 3 and 10 min after administration of aldosterone or placebo.
      Significant changes were found for systemic vascular resistance, cardiac output,
      and cardiac index, compared with the placebo group (Wilcoxon test, P < 0.02
      0.05). The effect of aldosterone dissipated within 10 min. The results are in
      line with the in vitro data cited above and consistent with earlier findings on
      acute cardiovascular effects of aldosterone, which have now been confirmed and
      extended by contemporary techniques. The hypotheses of rapid nongenomic in vivo
      effects of aldosterone are further substantiated by this study.

PMID- 9768658
TI  - A reliable endocrine test with human menopausal gonadotropins for diagnosis of
      true hermaphroditism in early infancy.
AB  - In true hermaphroditism diverse phenotypes and karyotypes are found; there are no
      distinctive laboratory features that can distinguish it from other intersex
      disorders, thus the diagnosis is made by the histological findings. Existence of
      Leydig cells is demonstrated by testosterone levels above the female range;
      however, presence of ovarian tissue cannot be ascertained because of the absence
      of a reliable functional test. Unless appropriate biopsies are performed or the
      whole gonad is removed, there is a risk of not diagnosing true hermaphroditism.
      To find a reliable test that can differentiate patients with true hermaphroditism
      from those with other intersex disorders, we investigated the estradiol (E2)
      response to human menopausal gonadotropins (hMG) in infants with genital
      ambiguity. These results were correlated with the histological findings. Eleven
      infants with genital ambiguity and four with a high scrotal testis were
      stimulated every 12 h with 2 IU/kg hMG. If E2 rose above 80 pg/mL (cut-off
      point), the test was discontinued; if after 7 days E2 remained below 80 pg/mL,
      the hMG dose was doubled and stimulation extended for 7 additional days. In five
      patients in whom true hermaphroditism was later histologically demonstrated, E2
      rose above 80 pg/mL. In two of them, ovarian tissue was removed and hMG
      stimulation repeated; no response above our cut-off point was observed during the
      second test. The maximal E2 response to hMG in the remaining 10 individuals was
      43 pg/mL; after laparotomy or gonadal biopsies no ovarian tissue was found. The
      hMG stimulation test can be considered a reliable and safe dynamic procedure for
      demonstrating the presence or absence of ovarian tissue in infants with genital
      ambiguity.

PMID- 9768659
TI  - Suppression of spermatogenesis in man induced by Nal-Glu gonadotropin releasing
      hormone antagonist and testosterone enanthate (TE) is maintained by TE alone.
AB  - GnRH antagonists plus testosterone (T) suppress LH and FSH levels and inhibit
      spermatogenesis to azoospermia or severe oligozoospermia. High-dose T treatment
      alone has been shown to be an effective male contraceptive (contraceptive
      efficacy rate of 1.4 per 100 person yr). Combined GnRH antagonist and T induces
      azoospermia more rapidly and at a higher incidence than T alone; this combination
      has therefore been proposed as a prototype male contraceptive. However, because
      GnRH antagonists are expensive to synthesize and difficult to deliver, it would
      be desirable to rapidly suppress sperm counts to low levels with GnRH antagonist
      plus T and maintain azoospermia or severe oligozoospermia with T alone. In this
      study, 15 healthy men (age 21-41 yr) with normal semen analyses were treated with
      T enanthate (TE) 100 mg im/week plus 10 mg Nal-Glu GnRH antagonist sc daily for
      12 weeks to induce azoospermia or severe oligozoospermia. At 12-16 weeks, 10 of
      15 subjects had zero sperm counts, and 14 of 15 had sperm counts less than 3 x
      10(6)/mL. The 14 who were suppressed on combined treatment were maintained on TE
      alone (100 mg/week im) for an additional 20 weeks. Thirteen of 14 subjects in the
      TE alone phase had sperm counts maintained at less than 3 x 10(6)/mL for 20
      weeks. Ten remained persistently azoospermic or had sperm concentration of 0.1 x
      10(6)/mL once during maintenance. Mean LH and FSH levels in the subjects were
      suppressed to 0.4+/-0.2 IU/L and 0.5+/-0.2 IU/L in the induction phase, which was
      maintained in the maintenance phase. The 1 subject who failed to suppress sperm
      counts during induction had serum LH and FSH reduced to 0.3 and 0.5 IU/L,
      respectively. The subject who failed to maintenance had LH and FSH suppressed to
      1.0 and 0.2 IU/L, respectively, during the induction phase but these rose to 1.6
      and 2.1 IU/L, respectively, during maintenance. Failure to suppress or maintain
      low sperm counts may be related to incomplete suppression of serum LH and FSH
      levels. We conclude that sperm counts suppressed with GnRH antagonist plus T can
      be maintained with relatively low dose TE treatment alone. This concept should be
      explored further in the development of effective, safe, and affordable hormonal
      male contraceptives.

PMID- 9768660
TI  - Short stature associated with high circulating insulin-like growth factor (IGF)
      binding protein-1 and low circulating IGF-II: effect of growth hormone therapy.
AB  - We report a case of short stature associated with high circulating levels of
      insulin-like growth factor (IGF)-binding protein-1 (IGFBP-10 and low levels of
      IGF-II responsive to pharmacological treatment with GH. Our patient suffered
      severe growth failure from birth (2.06 SD below the mean for normal full-term
      boys, and 5.2 and 7.3 SD below the mean at 5 and 10 months). Studies carried out
      before referral to our pediatric unit included normal 46,XY karyotype and normal
      encephalic imaging. Other endocrine and metabolic alterations and other systemic
      diseases were excluded. At 1.7 yr of age (length, 6.1 SD; weight, 4.6 SD; head
      circumference, 1.4 SD below the mean, respectively) the patient was referred to
      our pediatric unit. The baseline GH concentration was 31 microg/L, and the peak
      after an arginine load was 59.6 microg/L. In the same samples GH bioactivity was
      nearly superimposable (RIA/Nb2 bioactivity ratio = 0.9). Fasting insulin and
      glucose concentrations were 7.4 microU/mL and 65 mg/dL, respectively, both
      normally responsive to an oral glucose load. GH insensitivity was excluded by a
      basal IGF-I concentration (64 ng/mL) in the normal range for 0- to 5-yr-old boys
      and its increase after 2 IU/day hGH administration for 4 days. IGFBP-3 (0.5
      microg/mL) was slightly reduced, whereas IGFBP-1 (2218 and 1515 ng/mL in two
      different basal samples) was well above the normal values for age and was
      suppressible by GH (maximum suppression, -77% at 84 h) and glucose load (maximum
      suppression, -46% at 150 min). The basal IGF-II concentration was below the
      normal range (86 ng/mL), whereas IGFBP-2 was normal (258 ng/mL). Analysis of the
      promoter region of IGFBP-1 and IGF-II failed to find major alterations. Neutral
      gel filtration of serum showed that almost all IGF-I activity was in the 35- to
      45-kDa complex, coincident with IGFBP-1 peak, while the 150-kDa complex was
      absent, although the acid-labile subunit was normally represented. At 2.86 yr
      (height, 65.8 cm; height SD score, -7.3; height velocity SD score, -5) the
      patient underwent treatment with 7 IU/week human GH; after 4 months, the
      patient's height was 68.5 cm (height SD score, -6.9) corresponding to a growth
      velocity of 8.3 cm/yr (0.3 height velocity SD score). IGFBP-1 was reduced (216
      ng/mL), although still in the high range, whereas IGF-I (71 ng/mL), IGFBP-3 (0.62
      microg/mL), and IGF-II (111 ng/mL) were only slightly increased. The IGF-I
      profile showed activity in the 150-kDa region. In conclusion, we speculate that
      the increased IGFBP-1 values found in this patient produce 1) inhibition of IGF-I
      biological activity and, therefore, a resistance to IGF-I not due to a receptor
      defect for this hormone; 2) inhibition of formation of the circulating 150-kDa
      ternary complex and, therefore, an accelerated clearance rate of IGF peptides; 3)
      inhibition of the feedback action on GH, leading to increased GH levels, which
      could suggest the diagnosis of GH insensitivity syndrome; and 4) inhibition of
      body growth.

PMID- 9768661
TI  - Emergency and prolonged use of intravenous etomidate to control hypercortisolemia
      in a patient with Cushing's syndrome and peritonitis.
AB  - We report the emergency and prolonged use of etomidate to control circulating
      cortisol levels in a patient with Cushing's syndrome secondary to ectopic ACTH
      production from a pancreatic islet cell tumor. Duodenal perforation and
      peritonitis complicated an episode of salmonella septicemia, precluding the use
      of conventional oral medical adrenolytic therapy. Endogenous cortisol secretion
      was abolished by parenteral etomidate, allowing serum cortisol levels to be
      controlled with an iv infusion of hydrocortisone over an 8-week period in
      intensive care before definitive pancreatic surgery.

PMID- 9768662
TI  - Circulating iodide concentrations during and after pregnancy.
AB  - Early, indirect studies suggested that an important aspect of thyroid economy
      during pregnancy was a decline in plasma or serum inorganic iodide (PII)
      concentrations, but there is little information concerning circulating iodide
      concentrations as assessed by direct measurement. The present study was
      undertaken to determine the relationship between gestation and serum iodide
      concentrations as assessed by direct measurement of PII. PII concentrations,
      urinary iodide levels, and other parameters of thyroid economy were measured
      during the first, second, and third trimesters and after delivery in 16 women.
      Mean serum T4 concentrations were significantly higher in all 3 trimesters than
      those after delivery. Serum free T4 index concentrations were significantly
      higher in the first trimester than during later periods of gestation or after
      delivery, but serum TSH concentrations were not depressed in the first trimester.
      Serum thyroglobulin concentrations were similar during pregnancy and after
      delivery. There was wide variability in PII and urinary iodide concentrations
      during and after pregnancy, but there was no trend for PII concentrations to be
      depressed during pregnancy. Pregnancy, at least in iodine-sufficient regions,
      does not have an important influence on circulating concentrations of iodide.

PMID- 9768663
TI  - Insulin, insulin-like growth factor I (IGF-I), IGF-binding protein-1, growth
      hormone, and feeding in the newborn.
AB  - The relationship between GH, insulin-like growth factor I (IGF-I), IGF-binding
      protein-1 (IGFBP-1), and insulin may be critical to the understanding of
      variation in early growth, especially in the small for gestational age (SGA)
      baby. To investigate these relationships, we have undertaken 12-h hormone
      profiles in 26 babies (13 SGA) at a median of 4.5 days of age. GH levels were
      measured every 10 min; insulin and IGFBP-1 were measured every 20 min. Mean
      levels of these hormones and IGF-I levels (from a single sample) were related to
      size at birth. The GH data were analyzed by Pulsar and time series analysis to
      characterize hormone pulsatility and relationship with feeds. IGF-I levels
      correlated with birth weight and length (r2 = 0.47; P = 0.004, and r2 = 0.5; P =
      0.0005, respectively, after allowing for gestation), whereas mean GH levels were
      negatively related to birth size (r2 = -0.18; P = 0.04 and r2 = -0.2; P = 0.03
      for weight and length, respectively). No direct relationship between mean GH
      levels and IGF-I was identified. IGF-I levels were higher in appropriate for
      gestational age (AGA; mean +/- SD, 82+/-61 ng/mL) than in SGA (34+/-22 ng/mL; P =
      0.03) babies. Baseline (mean +/- SD, 25.9+/-11.9), mean (33.9+/-14.0), and peak
      (45.0+/-18.1 microg/L) GH levels were higher in SGA than in AGA babies [17.1+/
      8.2 (P = 0.04), 22.5+/-10.4 (P = 0.03), and 30.7+/-15.4 microg/L (P = 0.04),
      respectively]. Mean IGFBP-1 levels were also higher in SGA than AGA babies
      (157.4+/-90.7 vs. 62.7+/-43.8 ng/mL; P = 0.01). A positive correlation was
      identified between changes in insulin and coincident pulses of GH (r = 0.147; P <
      0.01), whereas there was an inverse relationship between insulin and IGFBP-1,
      with a lag time 120 min (r = -0.33; P < 0.0001). In conclusion, these studies
      indicate that the GH-IGF-I axis is closely related to feeding in the newborn. In
      SGA babies, low IGF-I and elevated IGFBP-1 reflect the slow growth, but elevated
      GH and rapid GH pulsatility may be a signal for lipolysis.

PMID- 9768664
TI  - Precocious pubarche, hyperinsulinism, and ovarian hyperandrogenism in girls:
      relation to reduced fetal growth.
AB  - Pronounced adrenarche with precocious pubarche (PP) in girls has been associated
      with hyperinsulinism and subsequent functional ovarian hyperandrogenism (FOH).
      Recently, pronounced adrenarche and insulin resistance have each been related to
      low birth weight. We have now tested the hypothesis that the frequent concurrence
      of PP with pronounced adrenarche, FOH, and hyperinsulinemia in girls may be
      secondary to separate relationships between these conditions and low birth
      weight. A total of 185 girls (aged 5-18 yr) without endocrinopathy or with PP and
      pronounced adrenarche with or without FOH were studied; mean serum insulin (MSI)
      concentrations were determined after a standardized oral glucose tolerance test.
      Birth weight SD scores [mean (SEM)] of control girls (0.38+/-0.08; n = 83) were
      higher (P < 0.0001) than those of PP girls (-0.81+/-0.13; n = 102). Among
      postmenarcheal PP girls, birth weight SD scores of girls without FOH (-0.25+/
      0.19; n = 25) were higher (P < 0.0001) than those in girls with FOH (-1.51+/
      0.28; n = 23). In pubertal girls (n = 145), MSI levels correlated negatively with
      birth weight SD scores (r = -0.48; P < 0.05), independently of PP. MSI levels in
      girls with birth weight below 1 SD (93+/-9 mU/L; n = 33) were higher (P < 0.0001)
      than those in girls with birth weight between -1 and +1 SD (52+/-2 mU/L; n = 94),
      whereas glycemia profiles were comparable. Integration of the aforementioned data
      suggests that there may be a sequence in the associations between reduced fetal
      growth and components of the postnatal endocrine system; minor fetal growth
      reduction appears to be associated with amplified adrenarche, whereas more
      pronounced prenatal growth restriction seem to precede FOH and hyperinsulinemia
      during adolescence. In conclusion, these findings corroborate the hypothesis that
      the frequent concurrence of PP (with pronounced adrenarche), FOH, and
      hyperinsulinemia in girls may result from a common early origin (low birth weight
      serving as a marker), rather than from a direct interrelationship later in life.

PMID- 9768665
TI  - Interactive effect of estradiol and vitamin D receptor gene polymorphisms as a
      possible determinant of growth in male and female infants.
AB  - An association between vitamin D receptor (VDR) gene polymorphism and body size
      has been observed in infants. We hypothesized that the estradiol receptor (ER)
      gene is another determinant of infant growth and that the effects of the VDR and
      ER genotypes may interact with each other. The ER genotype (PvuII and XbaI
      sites), VDR genotype (BsmI site), and body size during the first 2 yr of life
      were analyzed in 161 healthy Caucasian full-term babies homozygous for the BsmI
      polymorphism of the VDR gene (BB or bb). There was no significant association
      between ER polymorphism and 1) body weight in boys and girls, 2) body length in
      girls, or 3) body length in boys with a bb genotype. In contrast, ER polymorphism
      and body length were significantly associated in BB boys. Boys with the BBpp
      genotype were shorter at birth (P < 0.005) and at 10 months of age (P < 0.001)
      than boys with other genotypes. They were even shorter than girls with the same
      genotype. These results indicate some degree of interaction between the effects
      of the VDR and ER genes, leading to significant variations in body growth during
      infancy, especially in boys.

PMID- 9768666
TI  - A progesterone-induced endometrial homolog of a new candidate tumor suppressor,
      DMBT1.
AB  - We have previously prepared and characterized a subtracted library enriched for
      endometrial progesterone (P)-dependent genes in the rhesus monkey. One of the
      fragment clones (H3) that we selected for sequencing from this library was found
      to be homologous to human DMBT1, a recently isolated member of the scavenger
      receptor cysteine-rich superfamily and a new putative tumor suppressor. In this
      report, we provide evidence that H3 is the rhesus monkey homolog of DMBT1.
      Additional sequence data of H3 (1071 bp) showed a striking homology with DMBT1
      (92% identical). Semiquantitative kinetic PCR of estrogen-dominant vs. P-dominant
      endometrial complementary DNA populations showed that the H3 gene was up
      regulated 5-fold by normal secretory P levels. In situ hybridization with unique
      probes to H3 confirmed the up-regulation by P in the endometrium and a restricted
      expression in the stromal compartment. Another recent report suggested the
      presence of an endometrial tumor suppressor in the same chromosomal region as
      DMBT1 (10q23-26); deletions in this region were associated with endometrial
      cancers. Together, these studies potentially provide a molecular link to the
      protective effect of the action of P on unopposed estrogen exposure in
      reproductive tract cancers in women.

PMID- 9768667
TI  - Serum leptin concentrations in Caucasian and African-American girls.
AB  - Because African-American girls are heavier, taller, and mature earlier than
      Caucasian girls, we hypothesized that the serum leptin concentration differs
      between the two groups. Serum leptin concentrations were measured by immunoassay
      in 12-h fasted blood samples collected from 79 Caucasian and 57 African-American
      girls between 8 and 17 yr of age. Body composition was measured by dual-energy x
      ray absorptiometry, sexual maturity by physical examination, and physical fitness
      by treadmill testing. Serum leptin concentrations were positively correlated (P <
      0.01) with maturation, body fatness, and insulin and were higher (6.6 ng/mL, P <
      0.01) in the African-American girls after adjusting for age. The difference
      remained significant (P < 0.01) but was reduced to 3.2 ng/mL after controlling
      for differences in maturation, fat mass, and physical fitness. The higher serum
      leptin levels might play an important role in the accelerated growth and sexual
      maturation of African-American girls.

PMID- 9768668
TI  - Secretory mechanisms of growth hormone (GH)-releasing peptide-, GH-releasing
      hormone-, and thyrotropin-releasing hormone-induced GH release in patients with
      acromegaly.
AB  - The GH secretory mechanism of GH-releasing hexapeptide (GHRP-6), GHRH, and TRH
      were studied in vivo and in vitro in seven patients with acromegaly. In an in
      vivo study, these patients showed clear GH responses to single administration of
      GHRP (four of four patients), GHRH (seven of seven patients), and TRH (seven of
      seven patients) and enhanced responses to GHRP plus GHRH (two of four patients)
      or TRH plus GHRH (six of six patients). In an in vitro dispersed cell study, the
      majority of patients examined also showed clear GH responses to GHRP (four of
      four patients), GHRH (six of six patients), and TRH (four of four patients) and
      an enhanced response to GHRP plus GHRH (three of three patients) or TRH plus GHRH
      (three of four patients). In one patient (no. 3), GHRP plus forskolin (adenylate
      cyclase activator), but not GHRP plus phorbol 12-myristate 13-acetate (protein
      kinase C activator), additively enhanced the GH response. Nordihydroguaiaretic
      acid (NDGA; inhibitor of arachidonic cascade) inhibited GH release induced by
      GHRP, TRH, GHRH, TRH plus GHRH, or GHRP plus GHRH, but did not inhibit basal GH
      secretion. In contrast, NDGA distinctly elevated intracellular cAMP levels in
      another patient (no. 7) when coadministered with GHRP, GHRH, or GHRP plus GHRH,
      whereas cAMP levels were not modified by single administration of GHRP and NDGA.
      The GH response to the combined administration of GHRP and GHRH was synergistic
      in this patient, but was additive in the other two patients. It is concluded that
      GHRP, TRH, and GHRH directly stimulate in vivo and in vitro GH release from human
      somatotropinomas, and GHRP and TRH mainly exert their action through activation
      of the phosphatidylinositol-protein kinase C pathway, whereas GHRH exerts its
      action through the adenylate cyclase-protein kinase A pathway. These three agents
      seem to release GH via the arachidonic cascade.

PMID- 9768669
TI  - Collagen cross-link excretion during space flight and bed rest.
AB  - Extended exposure to weightlessness results in bone loss. However, little
      information exists as to the precise nature or time course of this bone loss.
      Bone resorption results in the release of collagen breakdown products, including
      N-telopeptide and the pyridinium (PYD) cross-links, pyridinoline and
      deoxypyridinoline. Urinary pyridinoline and deoxypyridinoline are known to
      increase during bed rest. We assessed excretion of PYD cross-links and N
      telopeptide before, during, and after long (28-day, 59-day, and 84-day) Skylab
      missions, as well as during short (14-day) and long (119-day) bed-rest studies.
      During space flight, the urinary cross-link excretion level was twice those
      observed before flight. Urinary excretion levels of the collagen breakdown
      products were also 40-50% higher, during short and long bed rest, than before.
      These results clearly show that the changes in bone metabolism associated with
      space flight involve increased resorption. The rate of response (i.e. within days
      to weeks) suggests that alterations in bone metabolism are an early effect of
      weightlessness. These studies are important for a better understanding of bone
      metabolism in space crews and in those who are bedridden.

PMID- 9768670
TI  - Exclusion of the adrenocorticotropin (ACTH) receptor (MC2R) locus in some
      families with ACTH resistance but no mutations of the MC2R coding sequence
      (familial glucocorticoid deficiency type 2).
AB  - Several mutations in the coding exon of the ACTH receptor (MC2R) gene have been
      reported in cases of familial glucocorticoid deficiency or FGD. However, many
      patients with a similar syndrome do not present any mutation in the coding region
      of this gene. This is the case in 11 families we have investigated. Patients in
      these families present the typical clinical features of FGD, but no mutation was
      found in the coding exon of the ACTH receptor. To determine whether mutations on
      MC2R gene, but outside the coding region, may be involved in FGD in these
      families, we have performed a linkage analysis. Using three markers flanking MC2R
      gene on chromosome 18, we were able to exclude linkage in a region of 12
      centimorgans around the gene. This result clearly indicates that FGD is
      genetically heterogeneous. Defects in gene(s) different from MC2R gene are
      implicated in this syndrome.

PMID- 9768671
TI  - Trafficking of androgen receptor mutants fused to green fluorescent protein: a
      new investigation of partial androgen insensitivity syndrome.
AB  - The naturally occurring mutations of the androgen receptor (AR), detected in
      patients with androgen insensitivity syndrome (AIS), are currently analyzed by in
      vitro assays. Unfortunately, these assays do not always permit the demonstration
      of a direct relationship between the in vitro activity of the receptor and the
      severity of the phenotype (in particular, for mutations detected in patients with
      partial AIS). We recently studied the trafficking of wild-type AR, fused to the
      green fluorescent protein (GFP) in living cells. In the present study, we applied
      this method for the analysis of AR mutants to find out whether it could be a
      complementary method of investigation of AIS. After construction of the GFP-AR
      mutant fusion proteins, the androgen-binding characteristics, nuclear transfer
      capacities, and transcriptional activities were evaluated. The nuclear transfer
      was quantified in the presence of various concentrations of dihydrotestosterone
      (DHT). We studied two mutants associated with partial AIS: G743V and R840C. The
      androgen-binding characteristics of both mutants were affected, in comparison
      with normal AR. Although the affinities were similar, the dissociation rate of
      GFP-AR-G743V was twice that of GFP-AR-R840C. In transcriptional assay, both
      mutants were active only at high concentrations of androgen. The nuclear
      trafficking of the mutants was evaluated by two parameters: 1) the rate of
      nuclear transfer; and 2) the maximal amount of receptors imported into the
      nucleus. At 10(-6) mol/L DHT, the GFP-AR mutants entered into the nucleus in a
      fashion similar to that of GFP-AR-wt. At 10(-7) mol/L DHT, the rate and maximal
      degree of nuclear import were both reduced, even more, for GFP-AR-G743V. The
      difference between mutants was more pronounced at 10(-9) mol/L DHT, because GFP
      AR-G743V entered into the nucleus with even slower kinetics. Though the androgen
      binding affinity and transcriptional activity assays did not reveal major
      differences between mutants, the dissociation rate and the trafficking capacity
      measurements permitted the activity of the mutants to be differentiated. We
      observed that the nuclear transfer capacities of these mutants are in correlation
      with the severity of the phenotype. The GFP-AR model provides an opportunity both
      to observe the dynamics of the hormone/receptor complex in living cells and to
      study the impact of the ligand-binding domain mutation, as opposed to certain in
      vitro techniques. Because the nuclear import capacity correlates well with the
      degree of androgen insensitivity, the GFP-AR is a useful complementary tool to
      understanding the phenotype/genotype relationship of AR function in patients with
      AIS.

PMID- 9768672
TI  - Complete thyroxine-binding globulin (TBG) deficiency produced by a mutation in
      acceptor splice site causing frameshift and early termination of translation (TBG
      Kankakee).
AB  - Fourteen T4-binding globulin (TBG) variants have been identified at the gene
      level. They are all located in the coding region of the gene and 6 produce
      complete deficiency of TBG (TBG-CD). We now describe the first mutation in a
      noncoding region producing TBG-CD. The proband was treated for over 20 yr with L
      T4 because of fatigue associated with a low concentration of serum total T4.
      Fifteen family members were studied showing low total T4 inherited as an X
      chromosome-linked trait, and affected males had undetectable TBG in serum.
      Sequencing of the entire coding region and promoter of the TBG gene revealed no
      abnormality. However, an A to G transition was found in the acceptor splice
      junction of intron II that produced a new HaeIII restriction site cosegregating
      with the TBG-CD phenotype. Sequencing exon 1 to exon 3 of TBG complementary DNA
      reverse transcribed from messenger RNA of skin fibroblasts from an affected male,
      confirmed a shift in the ag acceptor splice site. This results in the insertion
      of a G in exon 2 and causes a frameshift and a premature stop at codon 195. This
      early termination of translation predicts a truncated TBG lacking 201 amino
      acids.

PMID- 9768673
TI  - Augmentation of leptin synthesis and secretion through activation of protein
      kinases A and C in cultured human trophoblastic cells.
AB  - Leptin is a fat cell-derived hormone that regulates food intake and energy
      expenditure. We previously demonstrated that leptin is produced by nonadipose
      cells, i.e. by placental trophoblasts. We also reported that a human
      trophoblastic cell line, BeWo cells, expresses leptin gene and secretes leptin
      into culture media. To elucidate the regulatory mechanisms of leptin production
      by human trophoblasts, we investigated synthesis and secretion of leptin in BeWo
      cells and in explant cultures of human placental tissue. Leptin production and
      gene expression in BeWo cells were increased by treatment with forskolin. The
      forskolin-induced increase in leptin production was completely suppressed by H89,
      an inhibitor of protein kinase A. Leptin production and gene expression in BeWo
      cells were increased by treatment with phorbol myristate acetate (PMA). The PMA
      induced increase in leptin production was completely suppressed by H7 and
      staurosporine, both of which are inhibitors of protein kinase C. Leptin secretion
      from first trimester chorionic tissue was approximately 50-fold greater than that
      from term placental tissue. Leptin production and gene expression in explant
      cultures of placental tissue at both stages of pregnancy were augmented markedly
      by treatment with forskolin or PMA. The present study demonstrated augmentation
      of leptin production by protein kinase A and protein kinase C in cultured human
      trophoblasts, thereby leading to a better understanding of the regulatory
      mechanisms of leptin production in human trophoblasts in vivo.

PMID- 9768674
TI  - Mutational analysis of PHEX gene in X-linked hypophosphatemia.
AB  - Hypophosphatemic rickets is commonly an X-linked dominant disorder (XLH or HYP)
      associated with a renal tubular defect in phosphate transport and bone
      deformities. The XLH gene, referred to as PHEX, or formerly as PEX (phosphate
      regulating gene with homologies to endopeptidases on the X-chromosome), encodes a
      749-amino acid protein that putatively consists of an intracellular,
      transmembrane, and extracellular domain. PHEX mutations have been observed in XLH
      patients, and we have undertaken studies to characterize such mutations in 46
      unrelated XLH kindreds and 22 unrelated patients with nonfamilial XLH by single
      stranded conformational polymorphism and DNA sequence analysis. We identified 31
      mutations (7 nonsense, 6 deletions, 2 deletional insertions, 1 duplication, 2
      insertions, 4 splice site, 8 missense, and 1 within the 5' untranslated region),
      of which 30 were scattered throughout the putative extracellular domain, together
      with 6 polymorphisms that had heterozygosity frequencies ranging from less than
      1% to 43%. Single stranded conformational polymorphism was found to detect more
      than 60% of these mutations. Over 20% of the mutations were observed in
      nonfamilial XLH patients, who represented de novo occurrences of PHEX mutations.
      The unique point mutation (a-->g) of the 5'untranslated region together with the
      other mutations indicates that the dominant XLH phenotype is unlikely to be
      explained by haplo-insufficiency or a dominant negative effect.

PMID- 9768675
TI  - Expression of the growth hormone secretagogue receptor in pituitary adenomas and
      other neuroendocrine tumors.
AB  - Synthetic GH secretagogues (GHSs; GH-releasing peptides and their nonpeptide
      mimetics) stimulate GH release, activate the hypothalamo-pituitary-adrenal axis,
      and release PRL in vivo. Patients with acromegaly show an exuberant GH response
      to GHSs, whereas patients with pituitary-dependent ACTH-secreting tumors show an
      exaggerated rise in ACTH and cortisol. We, therefore, studied the presence of GHS
      receptor (GHS-R) messenger ribonucleic acid (RNA) in 38 human pituitary tumors of
      different cell types, 3 ectopic ACTH-secreting tumors, a pancreatic gastrinoma, 3
      insulinomas, and a non-secreting thymic carcinoid as well as in 7 normal
      pituitary glands. Certain pituitary tumors were also studied by in vitro cell
      culture with measurement of secreted GH, ACTH, PRL, FSH, LH, alpha-subunit, and
      TSH. RNA was extracted from tissue samples and, after RT, a duplex PCR reaction
      with primers for the GHS-R gene and for the housekeeping gene glyceraldehyde-3
      phosphate dehydrogenase was performed, allowing semiquantitation of GHS-R
      expression. All the somatotroph adenomas (n = 8) showed a 2-10 times higher
      expression of the GHS-R gene compared to normal pituitaries. Higher than normal
      expression was shown in 5 of 18 tumors from patients with ACTH-secreting
      pituitary adenomas and in 1 of 3 ectopic ACTH-secreting carcinoid tumors. Two of
      the pituitary ACTH-secreting adenoma samples showed completely absent expression
      of the GHS-R, 8 showed expression similar to that of normal pituitary tissue, and
      3 of the corticotroph adenoma tissue samples and 2 ectopic ACTH-secreting tumors
      showed a very low level of expression. One of 4 prolactinoma samples showed a
      high level of expression, 1 showed expression similar to that of normal
      pituitary, and 2 samples showed a very low level of expression. Nonfunctioning
      pituitary adenoma samples showed either absent or very low level expression of
      the GHS-R. The pancreatic gastrinoma sample showed expression similar to that of
      normal pituitary tissue, whereas 3 insulinomas showed low level expression of the
      GHS-R gene; a nonsecreting thymic carcinoid tumor showed no detectable
      expression. In summary, although GHS-R messenger RNA is abundant in human
      somatotroph adenomas, it is also present in other pituitary adenomas,
      particularly ACTH-secreting tumors. These findings may explain the in vivo
      responses to GHSs in patients harboring such tumors. It also appears from our
      study that GHS-R may be expressed in other neuroendocrine tumors.

PMID- 9768676
TI  - RET/PTC and RET tyrosine kinase expression in adult papillary thyroid carcinomas.
AB  - The prevalence of RET/PTC rearrangements in papillary thyroid carcinomas (PTCs)
      varies widely in different studies, and an association of RET/PTC presence with
      tumor behavior remains to be clarified. A prospective study of 50 adult PTCs
      examined, using RT-PCR, the prevalence of the 3 main RET rearrangements and also
      of RET tyrosine kinase (TK) domain sequence expression. The genetic findings were
      correlated with the MACIS clinical prognostic score and with individual clinical
      parameters. Three of the patients had been exposed to radiation in childhood or
      adolescence. Four of the PTCs contained RET/PTC1, confirmed by sequencing, and
      none contained RET/PTC2 or RET/PTC3. The prevalence of RET rearrangements overall
      was 8%, but in the subgroup of 3 radiation-exposed patients it was 66.6%.
      Interestingly, RET tyrosine kinase domain messenger ribonucleic acid was
      detectable in 70% of PTCs using RET exon 12/13 primers and was detectable in 24%
      of PTCs using RET exon 15/17 primers. RT-PCR for calcitonin and RET extracellular
      domain, however, was negative. There was no association between the presence or
      absence of RET/PTC in the patient's tumor and clinical parameters. We conclude
      that RET/PTC1 is the predominant rearrangement in PTCs from adults with a history
      of external irradiation in childhood. RET TK messenger ribonucleic acid
      expression is common in PTCs, using RT-PCR, and cannot be used to infer the
      presence of specific RET rearrangements or of RET activation.

PMID- 9768677
TI  - Expression of 5alpha-reductase in the human temporal lobe of children and adults.
AB  - Androgens exert important biological effects on the brain, and 5alpha-reductase
      plays a crucial role in androgen metabolism. Therefore, we investigated the
      expression of the two isozymes of 5alpha-reductase in the human temporal lobe to
      determine the predominant isoform and to elucidate the existence of possible sex
      differences and differences between children and adults. We studied biopsy
      materials from the temporal lobe of 34 women, 32 men, and 12 children.
      Quantification of 5alpha-reductase 1 and 2 messenger ribonucleic acid (mRNA) was
      achieved by competitive RT-PCR. 5Alpha-reductase activity was determined in
      tissue homogenates using [1,2-3H]androstenedione as the substrate. Only 5alpha
      reductase 1 mRNA was expressed in human temporal lobe tissue; 5alpha-reductase 2
      mRNA was not expressed. 5Alpha-reductase 1 mRNA concentrations did not differ
      significantly in the cerebral cortex of women [25.9+/-7.9 arbitrary units (aU);
      mean +/-SEM] and men (20.4+/-2.8 aU) or in the cerebral cortex (23.3+/-4.4 aU)
      and the subcortical white matter of adults (32.6+/-5.6 aU), but they were
      significantly higher in the cerebral cortex of adults than in that of children
      (6.4+/-2.3 aU; P < 0.005). The apparent Km of 5alpha-reduction did not show
      significant differences between the two sexes. In conclusion, 5alpha-reductase 1
      mRNA is expressed in the temporal lobe of children and adults, but 5alpha
      reductase 2 mRNA is not. 5Alpha-reductase 1 mRNA concentrations did not differ
      significantly in the sexes, but they were significantly higher in specimens of
      adults than in those of children.

PMID- 9768678
TI  - Low growth hormone-binding protein in infants with congenital hypothyroidism.
AB  - We evaluated the circulating levels of GH, insulin-like growth factor I (IGF-I),
      GH-binding protein (GHBP), and IGF-binding protein-3 (IGFBP-3) before L-T4
      therapy in 19 infants with congenital hypothyroidism (CH), aged 12-29 days,
      diagnosed by neonatal screening and in a group of age- and sex-matched control
      infants. The same parameters were reevaluated after several months of treatment.
      Serum GHBP was measured by the high performance liquid chromatography-gel
      filtration method; serum GH, IGF-I, and IGFBP-3 levels were determined by
      commercial kits. The hypothyroid patients, before beginning therapy, presented
      significantly lower GHBP values than controls (P < 0.0001); during treatment,
      these values increased significantly; however, after 6 months they were still
      significantly lower than control values (P < 0.01). The pretreatment levels of GH
      were not significantly different from control values; after 1 month of treatment,
      GH did not show the decrease observed in controls and, therefore, was
      significantly higher (P < 0.01). The pretreatment levels of IGF-I were not
      significantly different from control values, but were lower in patients with
      severe than in those with mild hypothyroidism. They decreased at about 4 months
      of life and became significantly lower than control values at about 7 months of
      age (P < 0.05). In conclusion, it may be hypothesized that the condition of CH
      induces a change in GHBP expression, perhaps beginning in fetal life. The
      intrauterine production of IGF-I seems to be independent of the levels of GHBP
      and partially affected by fetal thyroid function.

PMID- 9768679
TI  - Chronic antagonism of nuclear factor-kappaB activity in cytotrophoblasts by
      dexamethasone: a potential mechanism for antiinflammatory action of
      glucocorticoids in human placenta.
AB  - Circulating glucocorticoids are present in increasing quantities as human
      gestation progresses, peaking during labor whether it occurs before or at term.
      Although the precise role of glucocorticoids in pregnancy is not well defined, it
      is clear that glucocorticoids suppress inflammation in many cell types by
      antagonizing the acute stimulatory actions of members of the Rel/nuclear factor
      kappaB (NF-kappaB) family on cytokine gene expression. In the present study we
      tested the hypothesis that during pregnancy, glucocorticoids chronically suppress
      inflammation in the human placenta. Cytotrophoblasts obtained from human term
      placentas were maintained for 48 h in culture medium supplemented with 10%
      charcoal-stripped calf serum with and without 100 nmol/L dexamethasone (DEX).
      Enzyme-linked immunosorbent assay studies revealed that cytotrophoblasts
      constitutively express interleukin-8 (IL-8), a known mediator of placental
      inflammation, between 24-96 h of culture. A 48-h treatment of cytotrophoblasts
      with 100 nmol/L DEX significantly reduced the production of IL-8 to 24+/-1% of
      control levels (P < 0.01). DEX and cortisol mediated a dose-dependent inhibition
      of IL-8 expression, with ED50 values of 5 and 50 nmol/L, respectively. DEX
      treatment also significantly reduced levels of IL-6 and tumor necrosis factor
      alpha in culture medium, suggesting that glucocorticoids coordinately reduce
      cytokine levels in cytotrophoblasts. As cytokine expression is regulated by NF
      kappaB and activator protein-1 (AP-1) transcription factors, electrophoretic
      mobility shift assays (n = 4) were used to determine whether DEX treatment
      altered the binding of nuclear proteins from cytotrophoblasts to labeled
      oligonucleotides corresponding to the kappaB and AP-1 response elements. We
      observed that a 48-h treatment of cytotrophoblasts with 100 nmol/L DEX markedly
      reduced binding of nuclear extracts from cytotrophoblasts to the kappaB response
      element. DEX treatment promoted a relatively smaller reduction of binding to the
      AP-1 response element. Northern blotting experiments revealed that DEX treatment
      did not alter the level of IkappaB, p50, or p65 messenger ribonucleic acid,
      suggesting that the antiinflammatory action of glucocorticoid in cytotrophoblasts
      did not directly involve alterations in the level of NF-kappaB proteins. Our
      results demonstrate a novel chronic suppressive action of glucocorticoid on
      cytokine production and nuclear binding of NF-kappaB and AP-1 proteins in
      cytotrophoblasts, providing a potential mechanism through which glucocorticoids
      may suppress inflammation at maternal-fetal interfaces across gestation.

PMID- 9768680
TI  - Elevated nocturnal melatonin is a consequence of gonadotropin-releasing hormone
      deficiency in women with hypothalamic amenorrhea.
AB  - Elevated nocturnal melatonin is found in women with idiopathic hypogonadotropic
      hypogonadism (IHH), but it is not known whether this is implicated in the
      etiology of their GnRH deficiency. It is unlikely that nocturnal melatonin can be
      implicated in the etiology of the GnRH deficiency of Kallmann's syndrome (KS),
      because this condition is caused by defective neuronal migration in embryonic
      life. We therefore measured nocturnal melatonin in women with IHH and KS to
      determine whether it was elevated in one or both conditions and thereby to
      determine whether it was implicated as cause or consequence of GnRH deficiency.
      Four women with IHH, 3 women with KS, and 7 individually matched (age and body
      size) controls were recruited. Frequent day- and nighttime samples were taken for
      LH pulsatility studies. All patients showed absent or diminished LH pulsatility,
      compared with their respective controls. Samples were also taken over 24 h for
      melatonin and 6-sulphatoxymelatonin (the principle metabolite of melatonin and an
      independent marker of its secretion). Melatonin and 6-sulphatoxymelatonin levels
      were elevated in 6 of 7 patients (compared with their matched controls) and were
      significantly elevated in the KS group (compared with their controls). The
      finding of elevated nocturnal melatonin (and its metabolite) in GnRH-deficient
      women with KS (as well as IHH) suggests that nocturnal melatonin is elevated as a
      consequence of GnRH deficiency, irrespective of its etiology.

PMID- 9768681
TI  - Growth hormone (GH) response to GH-releasing peptide-6 in type 1 diabetic
      patients with exaggerated GH-releasing hormone-stimulated GH secretion.
AB  - In type 1 diabetes mellitus (DM 1), high GH basal levels and exaggerated GH
      responses to several stimuli, including GHRH, have been described. GH-releasing
      peptide-6 (GHRP-6) is a synthetic hexapeptide that specifically stimulates GH
      release, both in vitro and in vivo. The aim of this study was to evaluate the
      effects of GHRP-6 alone or in combination with GHRH on GH secretion in DM 1. Six
      type 1 diabetic males and six age-, sex-, and body mass index-matched control
      volunteers were studied. Each subject received GHRH (100 microg iv), GHRP-6 (90
      microg iv), and GHRH plus GHRP-6 on three separate days. GH peak values were
      higher in DM 1 patients than in control volunteers, after GHRH (52.2+/-9.8 vs.
      19.3+/-6.0 microg/L; P = 0.016), GHRP-6 (66.2+/-9.6 vs. 39.9+/-6.3 microg/L; P =
      0.05), and GHRH plus GHRP-6 (81.8+/-4.4 vs. 53.7+/-8.2 microg/L; P = 0.01). An
      additive GH response to combined administration of these two peptides was
      observed in diabetic patients. Serum insulin-like growth factor (IGF)-1 levels
      were diminished in DM 1, with respect to normal subjects (145.2+/-21.5 vs.
      269.7+/-42.0 microg/L; P = 0.01), whereas IGF-binding protein-3 levels were not
      significantly different between DM-1 and controls. In summary, GHRP-6 is a potent
      stimulus for GH secretion in DM 1. The combined administration of GHRP-6 plus
      GHRH constitutes the most powerful stimulus for GH secretion in DM 1. These
      patients exhibit a greater GH secretory capacity than normal subjects, probably
      caused by a diminished tone in the IGF-1 sustained negative feedback control
      exerted upon somatotroph responsiveness.

PMID- 9768682
TI  - Therapeutic usefulness of wild-type p53 gene introduction in a p53-null
      anaplastic thyroid carcinoma cell line.
AB  - Anaplastic thyroid carcinomas very often harbor the mutations in the tumor
      suppressor gene p53. We have previously shown that wild-type (wt) p53 gene
      introduction led to cell growth arrest, but not apoptosis, in p53-null anaplastic
      thyroid carcinoma cells. The present studies were designed to evaluate other
      therapeutic effects of wt-p53 gene introduction on p53-null thyroid carcinoma
      cells, as chemo- and radiosensitization and inhibition of angiogenesis have also
      been described recently as additional therapeutic advantages of wt-p53 gene
      introduction in tumor cells with p53 mutations. A p53-null anaplastic thyroid
      carcinoma cell line, FRO, and a FRO subline stably expressing a temperature
      sensitive (ts) mutant of p53 (p53Val138), tsFRO, were used. ts-p53 functions as
      mutant and wt at nonpermissive (37 C) and permissive (32 C) temperatures,
      respectively. tsFRO showed a prolonged cell doubling time compared to parental
      FRO when cultured at 32 C, but the cell growth rate was similar between FRO and
      tsFRO at 37 C. The cytotoxic and clonogenic assays demonstrated that although the
      sensitivity to three different anticancer agents (cisplatin, 5-fluorocytosine,
      and doxorubicin) was unaltered, radiosensitivity was enhanced in tsFRO compared
      to FRO at 32 C. Unexpectedly, in studies on angiogenesis, expression levels of
      vascular endothelial growth factor (an angiogenic factor) messenger ribonucleic
      acid were similar between FRO and tsFRO, and thrombospondin-1 (an antiangiogenic
      factor) messenger ribonucleic acid and protein levels were about 2.5-fold lower
      in tsFRO than FRO at 32 C, although any difference could not be detected in their
      ability to inhibit in vitro angiogenesis with the culture medium conditioned by
      tsFRO and FRO at 32 C. These results suggest that p53-defective thyroid
      carcinomas may benefit from the combination of p53 gene therapy and radiotherapy.
      However, further study will be necessary to clarify the pathological significance
      of thrombospondin-1 in angiogenesis and thyroid tumor growth.

PMID- 9768683
TI  - Fibronectin is required to prevent thyroid cell apoptosis through an integrin
      mediated adhesion mechanism.
AB  - Apoptosis or programmed cell death occurs in a wide variety of cell types when
      adhesion to extracellular matrix (ECM) is denied. Invasion and metastasis by
      tumor cells involve the loss of normal cell-ECM contacts and require independence
      from such control mechanisms. We studied whether the immortalized thyroid cell
      line TAD-2 is a model suitable to investigate thyroid cell-ECM interaction, and
      we analyzed the role of integrin-fibronectin (FN) interaction in apoptosis.
      Adhesion, spreading, and cytoskeleton organization in TAD-2 cultured cells were
      dependent upon integrin-FN interaction. Cell spreading and cytoskeletal
      organization were coupled to deposition of insoluble FN induced by serum.
      Expression of integrin-FN receptors was demonstrated by flow cytofluorometry with
      specific antibodies, and strong integrin-dependent adhesion was demonstrated by
      attachment assays to immobilized FN. Apoptosis, occurring in different culture
      conditions, was determined by cell morphology and DNA electrophoretic analysis
      and quantitated by flow cytometry in propidium iodide-stained cells. Thyroid
      cells underwent apoptosis in the presence of serum when adhesion was prevented by
      specific peptides that inhibit integrin binding to FN (RGD-containing peptides)
      or by coating the culture plates with agar. In serum-free cultures, apoptosis was
      prevented by insoluble FN immobilized on the plates, but not by soluble FN. These
      results suggest that the TAD-2 cell line is a good model to study thyroid cell
      ECM interaction, that FN, assembled into insoluble matrix, is required for
      cytoskeletal organization and to prevent thyroid cell apoptosis, and that
      integrin-mediated adhesion is involved in this process.

PMID- 9768684
TI  - Change of peripheral levels of pituitary hormones and cytokines after injection
      of interferon (IFN)-beta in patients with chronic hepatitis C.
AB  - Interferons (IFNs) are now in use worldwide for the treatment of chronic viral
      hepatitis. Unfortunately, various side effects of IFNs have been reported.
      Because cytokines, which include IFNs, can affect endocrine function,
      endocrinological abnormalities are sometimes observed in patients treated with
      IFNs. We examined the effects of IFN-beta on peripheral levels of pituitary and
      adrenal hormones and cytokines. Six million international units of IFN-beta
      dissolved in glucose solution was injected for 30 min. As a control study,
      glucose solution without IFN-beta was injected. Pituitary hormones (ACTH, GH,
      TSH, prolactin (PRL), LH, FSH, and arginine-vasopressin (AVP)), cortisol, and
      cytokines such as interleukin (IL)-1, IL-6, tumor necrosis factor-alpha (TNF),
      and interleukin-1 receptor antagonist (IL-1ra) were measured before and after IFN
      beta injection. The study was carried out on 14 patients with chronic hepatitis
      type C who were under treatment with IFN-beta. All studies were performed when
      the patients were afebrile. None of the patients had any endocrine or autoimmune
      diseases. Plasma ACTH levels increased significantly at 60-120 min after IFN-beta
      injection compared with the levels before IFN-beta injection and in the control
      study using glucose injection. Plasma cortisol levels increased after IFN-beta
      injection, in parallel with plasma ACTH elevation. Serum GH levels increased
      significantly at 120 min after IFN-beta injection. All the increased hormones
      including ACTH, cortisol, and GH, were decreased at the end of the study-180 min
      after IFN-beta injection. Serum levels of TSH, PRL, LH, FSH, and AVP were not
      changed significantly by IFN-beta injection. Plasma IL-1 and TNF levels did not
      change after IFN-beta injection, while IL-6 and IL-1ra were elevated
      significantly. The increases in IL-6 and IL-1ra were gradual, reaching their peak
      levels at 180 min after IFN-beta injection. However there were no correlations
      between the hormones measured in this study and the levels of IL-6 or IL-1ra. It
      would seem that IFN-beta has direct or indirect stimulatory effects for ACTH and
      GH without mediation of the cytokines. These in vivo results are important for
      investigating the relationship between endocrine and cytokine systems in humans.

PMID- 9768685
TI  - Mutations in the genomic deoxyribonucleic acid for SLC3A1 in patients with
      cystinuria.
AB  - Cystinuria is an inherited transport disorder characterized by defective renal
      resorption of cystine and other dibasic amino acids. We have studied the
      occurrence of mutations in the SLC3A1 gene, which codes for a dibasic amino acid
      transporter-like protein, in 33 unrelated cystinurics. We found mutations in 34
      of the 66 chromosomes studied. There were 14 different mutations in our study
      population, 8 of which had not been previously described. Of these new mutations,
      4 were missense mutations: G1934C, C1259G, T1607G, and G1373A. The other 4
      mutations consisted of a single base insertion mutation (2022 ins T), a single
      base deletion mutation (163 del C), a 23-base deletion mutation (del 782A-804A),
      and a complex mutation that consisted of a 36-base deletion (del C431-3 to T463)
      and a duplication insertion of 468 T to 474 A after nucleotide 474.

PMID- 9768686
TI  - Adrenarche results from development of a 3beta-hydroxysteroid dehydrogenase
      deficient adrenal reticularis.
AB  - Adrenarche is the increased adrenal production of dehydroepiandrosterone (DHEA)
      and dehydroepiandrosterone sulfate (DHEAS) that occurs during the prepubertal
      period. To date, the exact mechanism initiating adrenarche is unknown, although
      many factors have been postulated. In the present study, we examined the
      hypothesis that alterations in intra-adrenal expression of 3beta-hydroxysteroid
      dehydrogenase (3betaHSD) or 21-hydroxylase (CYP21) within the inner reticularis
      zone leads to the increased production of 19-carbon (C19) steroids. After
      conversion of cholesterol to pregnenolone, 17alpha-hydroxylase/17,20-lyase
      (CYP17) can metabolize pregnenolone through to DHEA. The enzyme 3betaHSD competes
      for substrate with CYP17 and effectively removes steroid precursor from the
      pathway leading to DHEA. On the other hand, deficiency in CYP21 expression is
      known to cause excessive production of adrenal C19 steroids, suggesting that
      CYP21 could play a role in adrenarche. Thus, a decrease in 3betaHSD or CYP21
      expression would allow substrate to flow toward the synthesis of DHEA. To
      determine whether adrenarche results from a decreased expression of 3betaHSD or
      CYP21 in the reticularis, immunohistochemical localization of 3betaHSD and CYP21
      was performed, and staining intensities compared using adrenal glands from
      children ages 4 months to 4 yr (n = 12), ages 5-7 yr (n = 9), ages 8-13 yr (n =
      9), and adults ages 25-56 yr (n = 8). There were no differences in the zonal
      expression of CYP21. No difference in 3betaHSD staining was observed between the
      glomerulosa and fasciculata from any age group. However, children age 8 yr and
      older show a significant decrease in 3betaHSD expression in reticularis as
      compared with the fasciculata. No significant difference was noted for 3betaHSD
      levels between the fasciculata and reticularis for children age 7 yr or younger.
      The level of 3betaHSD expression in the reticularis continued to decrease in the
      adult adrenals examined. These findings suggest that as children mature there is
      a decreased level of 3betaHSD in the adrenal reticularis that may contribute to
      the increased production of DHEA and DHEAS seen during adrenarche.

PMID- 9768687
TI  - Potential for estrogen synthesis and action in human normal and neoplastic
      thyroid tissues.
AB  - To investigate the potential of intracrine or paracrine estrogen synthesis and
      action in the human thyroid gland and thyroid tumors, the presence of the
      messenger ribonucleic acids (mRNAs) of both cytochrome P450 aromatase (P450arom)
      and estrogen receptor (ER) was investigated by RT-PCR with primers designed on
      the respective coding regions and Southern hybridization analysis with specific
      probes in neoplastic (n = 42), hyperplastic (n = 7), and adjacent histologically
      normal thyroid tissues (n = 33) obtained from 43 female and 7 male patients. Most
      thyroid tissues were positive for both mRNAs, but 2 normal and 3 neoplastic
      tissues were negative for P450arom mRNA only, 3 normal and 1 hyperplastic tissues
      were negative for ER mRNA only, and 2 normal tissues were double negative. In
      some patients, P450arom mRNA was absent in either the neoplastic tissue or the
      normal one. Single and double negative samples were relatively more frequent in
      men (n = 4) than in women (n = 7). All negative samples were positive for beta
      actin mRNA. RT-PCR amplification and Southern blotting of promoter-specific
      untranslated 5'-termini revealed that the human thyroid gland and tumors mainly
      use the ovarian-type promoter, promoter II, for CYP19 expression. Transcripts
      with either exon I.4 or I.1 were present only in some samples and in very low
      copy number. When 18 neoplastic samples with their surrounding normal tissues
      were analyzed immunohistochemically, 57% of those that were positive for P450arom
      mRNA also had a positive immunoresponse for the corresponding protein. In the
      case of ER, the percentage was 58%. Immunostaining for P450arom was often
      particularly intense in neoplastic samples. When 3 adenomata and 1 papillary
      cancer were incubated with [1,2,6,7-3H]testosterone, 17beta-estradiol could be
      radiochemically identified with a maximal yield of 10.5 fmol/mg x h. In
      conclusion, the human thyroid gland appears to have the potential for both
      estrogen synthesis and intracrine or paracrine estrogen responsiveness, which
      seem to be greater in women than men and may become enhanced with the process of
      tumorigenesis.

PMID- 9768688
TI  - 17Beta-hydroxysteroid dehydrogenase types 1 and 2 in human placenta: an
      immunohistochemical study with correlation to placental development.
AB  - In estrogen metabolism, the enzymatic properties of the 17beta-hydroxysteroid
      dehydrogenase (17betaHSD) isozymes play very important roles in steroid hormone
      metabolism in various tissues, including the placenta. 17betaHSD type 1 catalyzes
      primarily the reduction of estrone (E1) to estradiol (E2), whereas 17betaHSD type
      2 catalyzes primarily the oxidation of E2 to E1. In this study, we examined
      immunohistochemical localization of 17betaHSD types 1 and 2 in human placenta (31
      cases) ranging from 4-40 weeks gestation. The immunoreactivity of 17betaHSD type
      1 was exclusively detected in syncytiotrophoblast from 4 weeks gestation to term
      placenta. Immunoreactivity of 17betaHSD type 2 first appeared in endothelial
      cells of intravillous vessels at 12 weeks gestation, and the number of 17betaHSD
      type 2-positive endothelial cells markedly increased up to 19 weeks, then reached
      a plateau. We quantitatively evaluated the 17betaHSD type 2-positive endothelial
      cells in chorionic villi and determined the ratio of 17betaHSD type 2-positive
      endothelial cells using immunohistochemistry of CD34, an endothelial antigen, in
      serial mirror tissue sections and subsequent image analysis using CAS 200. CD34
      was detected from 4 weeks gestation, and its positive areas continued to increase
      toward term. The 17betaHSD type 2-positive area per CD34-positive area markedly
      increased from 13 weeks gestation and reached a plateau at 19 weeks gestation, in
      which almost all endothelial cells were positive for 17betaHSD type 2. 17BetaHSD
      type 2, therefore, is considered to prevent the passage of excessive estrogens
      into the fetal circulation at endothelial cells of the intravillous fetal
      capillaries by catalyzing the inactivation ofE2 to E1.

PMID- 9768689
TI  - Corticotropin-releasing hormone and proopiomelanocortin-derived peptides are
      present in human myometrium.
AB  - CRH and POMC-derived peptides are produced at a number of intrauterine sites in
      both the nonpregnant and pregnant states. It is hypothesized that CRH and POMC
      derived peptides may be produced locally by the uterus to modulate myometrial
      contractility. This study has examined the distribution of these peptides in
      human uterine tissue during the ovulatory cycle and pregnancy. The
      immunoperoxidase staining method was used to localize CRH and POMC-derived
      peptides: ACTH, beta-endorphin, and alphaMSH. Immunoreactive (IR-) CRH and IR
      POMC-derived peptides, beta-endorphin and alphaMSH, were observed in the
      myometrial smooth muscle, vascular smooth muscle, endometrial glandular
      epithelium, and luminal epithelium of the nonpregnant uterus (n = 17). Staining
      for IR-CRH did not change during the cycle from the proliferative (n = 8) to the
      secretory phases (n = 9). Conversely, staining for IR-beta-endorphin and IR
      alphaMSH was only observed during the secretory phase of the cycle (n = 9). In
      uterine tissue obtained from pregnant women (n = 20) IR-CRH was present in the
      myometrial smooth muscle, vascular smooth muscle, decidua, and glandular
      epithelium. IR-POMC-derived peptides were not detectable at any uterine site
      during pregnancy (n = 20). IR-CRH was measurable in myometrial extracts collected
      from pregnant women undergoing cesarean section (20.9+/-3.8 ng/g wet wt; n = 7)
      and from nonpregnant premenopausal women undergoing hysterectomy (7.7+/-2.1 ng/g
      wet wt; n = 6). IR-CRH concentrations significantly increased with pregnancy.
      Levels of messenger ribonucleic acid encoding for CRH were examined in
      nonpregnant (n = 4) and pregnant (n = 10) myometrial smooth muscle and were also
      significantly increased with pregnancy. This study has demonstrated that levels
      of CRH and POMC peptide in human uterine tissue change with pregnancy and that
      CRH is produced locally by myometrial smooth muscle cells. These studies are
      consistent with the possibility that the CRH peptide has an autocrine/paracrine
      activity during pregnancy and labor that may be related to the modulation of
      myometrial contractility.

PMID- 9768690
TI  - Cyclic adenosine 3',5'-monophosphate-responsive element modulator gene expression
      in germ cells of normo- and oligoazoospermic men.
AB  - In about one third of infertile men the cause of impaired spermatogenesis is not
      known. Spermatogenesis appears to be mediated at least in part by the pituitary
      gonadotropins, which activate the cAMP-dependent signaling pathway. The end point
      of this pathway is the activation of nuclear transcription factors, such as cAMP
      responsive element-binding protein and cAMP-responsive element modulator (CREM).
      These factors, upon binding to gene sequences identified as cAMP response
      elements, modulate the expression of germ cell-specific genes that, in turn,
      promote the completion of spermatogenesis. The expressions of the cAMP-responsive
      element-binding protein and CREM genes create different isoforms, which can be
      divided into two groups: activators or repressors of gene regulation. Only CREM
      repressors are expressed in premeiotic germ cells in mice, whereas a switch to
      the expression of the CREM activator tau is observed from postmeiotic germ cells
      onward. Completion of germ cell maturation appears to be dependent on this
      phenomenon. Recently, mice lacking CREM gene expression have been generated.
      These animals were infertile and presented a developmental arrest of germ cell
      maturation at the stage of early spermatid. In this report we demonstrate that
      CREM gene expression also occurs in human germ cells. In particular, we
      determined by RT-PCR that a switch from the expression of CREM repressors to CREM
      activators is present in postmeiotic germ cells in normospermic men. Conversely,
      in oligoazoospermic patients only the expression of CREM repressors was detected.
      These data were confirmed by in situ hybridization studies in which transcripts
      for CREM activators were detected in postmeiotic germ cells in testis specimens
      showing conserved spermatogenesis, but not in specimens showing maturation arrest
      at the spermatid stage. Thus, our results indicate that the lack of a switch in
      the expression of CREM gene isoforms may be related to impaired spermatogenesis
      in humans.

PMID- 9768691
TI  - Phenotypic variability in familial combined pituitary hormone deficiency caused
      by a PROP1 gene mutation resulting in the substitution of Arg-->Cys at codon 120
      (R120C).
AB  - As pituitary function depends on the integrity of the hypothalamic-pituitary
      axis, any defect in the development and organogenesis of this gland may account
      for a form of combined pituitary hormone deficiency (CPHD). A mutation in a
      novel, tissue-specific, paired-like homeodomain transcription factor, termed
      Prophet of Pit-1 (PROP1), has been identified as causing the Ames dwarf (df)
      mouse phenotype, and thereafter, different PROP1 gene alterations have been found
      in humans with CPHD. We report on the follow-up of two consanguineous families (n
      = 12), with five subjects affected with CPHD (three males and two females) caused
      by the same nucleotide C to T transition, resulting in the substitution of Arg-
      >Cys in PROP1 at codon 120. Importantly, there is a variability of phenotype,
      even among patients with the same mutation. The age at diagnosis was dependent on
      the severity of symptoms, ranging from 9 months to 8 yr. Although in one patient
      TSH deficiency was the first symptom of the disorder, all patients became
      symptomatic by exhibiting severe growth retardation and failure to thrive, which
      was mainly caused by GH deficiency (n = 4). The secretion of the pituitary
      derived hormones (GH, PRL, TSH, LH, and FSH) declined gradually with age,
      following a different pattern in each individual; therefore, the deficiencies
      developed over a variable period of time. All of the subjects entered puberty
      spontaneously, and the two females also experienced menarche and periods before a
      replacement therapy was necessary.

PMID- 9768692
TI  - Unchanged testosterone production rates in growth hormone-treated healthy men.
AB  - The effect of biosynthetic human GH on the production rates of testosterone was
      determined in healthy men (n = 7) using the stable isotope dilution technique and
      mass spectrometry. 1Alpha,2alpha-d-testosterone (20 microg/h) was infused for 10
      h (0800-1800 h). Blood samples obtained at 20-min intervals from 1400-1800 h were
      pooled during two 2-h periods. Subsequently, each volunteer received a daily dose
      of biosynthetic human GH (4 IU/day sc) for 7 days. This resulted in a rise in
      plasma concentrations of somatomedin-C from, basal, 0.67+/-0.13 U/mL to 1.20+/
      0.2 U/mL on day 7 (P < 0.0001). Testosterone production rates (basal: 209.9+/
      31.0 microg/h) were unchanged by treatment with GH (day 7: 192.2+/-30.1
      microg/h). In healthy men, short-term treatment with sc GH does not influence
      endogenous testosterone production rates.

PMID- 9768693
TI  - Systematic mutation screening of the pro-opiomelanocortin gene: identification of
      several genetic variants including three different insertions, one nonsense and
      two missense point mutations in probands of different weight extremes.
AB  - Pro-opiomelanocortin (POMC) is the precursor of melanocortins
      (adrenocorticotropin: ACTH, beta-endorphin, beta-lipotropin: beta-LPH,
      corticotropin like intermediate peptide, alpha-, beta- and gamma-melanocyte
      stimulating hormone: alpha-, beta- and gamma-MSH) some of which act in the brain
      to reduce food intake and are potential mediators of leptin action. Recently,
      three different mutations in the POMC gene (POMC) were identified in two
      unrelated children that lead to early-onset extreme obesity, adrenal
      insufficiency, and red hair pigmentation. In the present study we systematically
      screened the coding region of POMC in 96 extremely obese children and
      adolescents, 60 healthy underweight individuals and 46 patients with anorexia
      nervosa (AN) and identified several variants. a) A 9 and an 18 base pair
      insertion (9bp and 18bp: AGC AGC GGC and AGC AGC GGC AGC AGC GGC, respectively,
      between codon 73 and 74; 1,2). These in-frame variants lead to the insertion of
      three or six amino acids (Ser-Ser-Gly; Ser-Ser-Gly-Ser-Ser-Gly) carboxy-terminal
      to gamma-MSH. Frequencies of the 9bp insertion allele varied between 3 and 5%
      among the different study groups (Pearson's chi2 P>0.5). b) Both an out-of-frame
      6 bp insertion (within codon 176: GGG CCC) leading to the insertion of two amino
      acids (Arg-Ala) and a premature stop-codon (G-7316-T: Glu-180-Stop) within the
      gamma-LPH sequence were maternally inherited in an obese female proband. This
      proband inherited another missense mutation from her father (Glu-188-Gly). c) A
      missense mutation (G-7016-A; Asp-80-Asn) was observed in a single patient with AN
      who also harboured the 9bp insertion on a paternally derived haplotype. d) The
      allelic co-occurence of two silent mutations (C-6982-T and C-7285-T) was detected
      in two obese subjects. e) Two further silent mutations (C-3832-T; C-7111-G) were
      detected in an underweight and an obese subject, respectively. We conclude that
      the POMC gene harbors several different polymorphisms and mutations, none of
      which can readily be associated with the phenotypes under study.

PMID- 9768694
TI  - Synergistic effects of feeding and dexamethasone on serum leptin levels.
AB  - The objectives of this study were to determine the time course of the stimulatory
      effect of dexamethasone on serum leptin and whether it depends on food intake.
      Dexamethasone (4mg) was administered I.V. over 1 minute to healthy human
      volunteers (n=8) under fasting and feeding conditions (2000 kcal given at three
      meals over 7 hours). At 10 hours, serum leptin levels were increased only in the
      fed subjects (delta leptin 10.6+/-1.6 vs -2.4+/-1.9 ng/ml, p=0.01, n=8). To
      assess the interactive effect of food and dexamethasone on serum leptin, a
      subgroup (n=4) was studied under 4 conditions: 1) dexamethasone/fast; 2)
      dexamethasone/food; 3) saline/fast; 4) saline/food. Serum leptin declined from
      baseline under the fasting conditions, with or without dexamethasone. Feeding
      prevented the drop in serum leptin. In the dexamethasone/food condition, leptin
      levels rose from baseline after 7 hours and doubled after 10 hours (p<0.05). The
      rise in serum leptin was significantly greater in the food/dexamethasone
      condition compared to all other conditions (p<0.05). In summary, dexamethasone
      has no independent effect on serum leptin in the absence of food intake. Rather,
      dexamethasone appears to potentiate the food-induced increase in serum leptin.
      This synergism may be mediated by insulin and/or other factors associated with
      food ingestion.

PMID- 9768695
TI  - Immunohistochemical localization of somatostatin receptor sst2A in human
      pancreatic islets.
AB  - Somatostatin and octreotide inhibit endocrine pancreatic functions in man, via
      specific somatostatin receptors. However, the cellular distribution of the
      different somatostatin receptor subtype proteins has not been determined in the
      human pancreas. Here, the immunohistochemical distribution of the sst2A receptor
      was investigated using the sst2A receptor specific anti-peptide antibody R2-88 in
      cryostat as well as in formalin-fixed paraffin-embedded sections of human
      pancreatic tissue, and compared with insulin, glucagon and somatostatin
      immunostaining of adjacent sections. All pancreatic islets were immunostained
      with R2-88. Most islet cells were labeled: the sst2A receptors were present in
      insulin as well as glucagon producing cells, but were not detected in intra-islet
      vessels nor in adjacent acinar tissue. Absorption of the sst2A antibody with 100
      nM of the antigen peptide abolished specific staining in tissue sections.
      Immunohistochemical staining with R2-88 correlated with the labeling observed
      after receptor autoradiography using the sst2-preferring radioligand, 125I-Tyr3
      octreotide. Therefore, the clinical efficacy of octreotide on glucagon and
      insulin release can be explained by the presence of sst2A receptors in human A
      and B pancreatic islet cells. Moreover, absence of sst2A receptors in human
      acinar tissue suggests that the action of somatostatin on pancreatic exocrine
      secretion is mediated either indirectly or through a different somatostatin
      receptor subtype on acinar cells.

PMID- 9768696
TI  - Cortisol, androstenedione (A4), dehydroepiandrosterone sulphate (DHEAS) and 17
      hydroxyprogesterone (17OHP) responses to low doses of (1-24)ACTH.
AB  - The dose of 250 microg used in the standard short synacthen test is
      supraphysiological and lower doses may provide a more sensitive test. We examined
      steroid responses to 125ng/m2, 250ng/m2 and 500 ng/m2 (1-24)ACTH in 6 normal
      males, looking at effects of dose and the within- and between-subject
      coefficients of variation (CV). Subjects were given each dose 3 times, blood
      samples were taken at 10 minute intervals. There was a dose response relationship
      between dose of (1-24)ACTH and peak values for cortisol and 17OHP (p<0.05). There
      was no difference between peaks of A4 at different doses and no clear peaks were
      reached for DHEAS. 86% of the peaks for 17OHP, 63% for A4 and 25% for cortisol
      were at 10 minutes and 14%, 29% and 65% respectively at 20 mins (p=0.001). Within
      subject CV for cortisol was 12.6% and between subject 10.1%. Tests of adrenal
      function using low doses of (1-24)ACTH have acceptable between- and within
      subject CV for peak values with a dose as low as 125 ng/m2 (1-24)ACTH. Protocols
      for low dose synacthen tests, with traditional sampling at zero, 30 and 60
      minutes or even as shown here at 10 minute intervals, fail to fully define the
      changes in steroid levels following adrenal stimulation. More frequent blood
      sampling will be needed to accurately detect peak levels in particular of 17OHP
      and A4.

PMID- 9768697
TI  - Estrogen receptor beta: mine is longer than yours?

PMID- 9768698
TI  - Coming of age in endocrinology.

PMID- 9768699
TI  - A never-ending story of an insufficient iodine status without mandatory
      iodization of foods?--A German experience.

PMID- 9768700
TI  - Increased plasma 17-hydroxyprogesterone response to ACTH in patients with
      nonhyperfunctioning adrenal adenomas is not due to a deficiency in 21-hydroxylase
      activity.

PMID- 9768701
TI  - Ovulation and spinal bone mineral density.

PMID- 9768702
TI  - Comment on marked improvement in bone mass after parathyroidectomy in osteitis
      fibrosa cystica.

PMID- 9768703
TI  - Comment on apoptosis and Fas expression in human fetal membranes.

PMID- 9768704
TI  - New Doppler echocardiographic applications for the study of diastolic function.
AB  - Doppler echocardiography is one of the most useful clinical tools for the
      assessment of left ventricular (LV) diastolic function. Doppler indices of LV
      filling and pulmonary venous (PV) flow are used not only for diagnostic purposes
      but also for establishing prognosis and evaluating the effect of therapeutic
      interventions. The utility of these indices is limited, however, by the
      confounding effects of different physiologic variables such as LV relaxation,
      compliance and filling pressure. Since alterations in these variables result in
      changes in Doppler indices of opposite direction, it is often difficult to
      determine the status of a given variable when a specific Doppler filling pattern
      is observed. Recently, color M-mode and tissue Doppler have provided useful
      insights in the study of diastolic function. These new Doppler applications have
      been shown to provide an accurate estimate of LV relaxation and appear to be
      relatively insensitive to the effects of preload compensation. This review will
      focus on the complementary role of color M-mode and tissue Doppler
      echocardiography and traditional Doppler indices of LV filling and PV flow in the
      assessment of diastolic function.

PMID- 9768705
TI  - Effects of thrombolytic therapy in acute inferior myocardial infarction with or
      without right ventricular involvement. HIT-4 Trial Group. Hirudin for Improvement
      of Thrombolysis.
AB  - OBJECTIVES: This study assessed the prognostic impact of right ventricular
      involvement (RVI) in streptokinase-treated patients with inferior acute
      myocardial infarction (AMI) stratified for small or large AMI. BACKGROUND: Only
      scant data exist from small studies about the impact of reperfusion therapy on
      survival in patients with RVI during inferior AMI. METHODS: Right ventricular
      involvement was assessed by ST-segment elevation > or =0.1 mV in lead V4R and
      infarct size by the extent of ST-segment deviation on the baseline
      electrocardiogram: small AMI=sum ST-segment elevation < or =0.8 mV and no
      precordial ST-segment depression (small ST); large AMI=presence of precordial ST
      segment depression or sum ST-segment elevation >0.8 mV (large ST) in 522 inferior
      AMI patients of the Hirudin for Improvement of Thrombolysis (HIT-4) Trial. In 187
      patients, 90-min coronary angiography was performed. RESULTS: Right ventricular
      involvement was present in 169 patients (32%). Higher 30-day cardiac mortality
      rates with RVI (5.9% vs. 2.5%) were related to larger infarct size rather than to
      RVI. For large ST, a proximal right coronary artery lesion was observed in 52%
      with and in 23% without RVI. Patency rates at 90 min were similar (54% vs. 52%).
      In the 28% of patients who had small ST, cardiac mortality was less than 1%
      irrespective of the presence of RVI. Coronary artery lesions were mostly located
      distally. Patency rates were 27% with and 80% without RVI. CONCLUSIONS: ST
      segment elevation of > or =0.1 mV in V4R in inferior AMI patients is associated
      with larger infarct size and higher 30-day mortality rates. Right ventricular
      involvement is not an independent predictor of survival. In patients with small
      ST, cardiac mortality is low, even if ST V4R is > or =0.1 mV.

PMID- 9768706
TI  - Treatment of right ventricular infarction: thrombolytic therapy, coronary
      angioplasty or neither?

PMID- 9768707
TI  - Patients treated by cardiologists have a lower in-hospital mortality for acute
      myocardial infarction.
AB  - OBJECTIVES: We sought to determine the effect of specialty care on in-hospital
      mortality in patients with acute myocardial infarction. BACKGROUND: There has
      been increasing pressure to limit access to specialists as a method to reduce the
      cost of health care. There is little known about the effect on outcome of this
      shift in the care of acutely ill patients. METHODS: We analyzed the data from
      30,715 direct hospital admissions for the treatment of acute myocardial
      infarction in Pennsylvania in 1993. A risk-adjusted in-hospital mortality model
      was developed in which 12 of 20 clinical variables were significant independent
      predictors of in-hospital mortality. To determine whether there were factors
      other than patient risk that significantly influenced in-hospital mortality,
      multiple logistic regression analysis was performed on physician, hospital and
      payer variables. RESULTS: After adjustment for patient characteristics, a
      multiple logistic regression analysis identified treatment by a cardiologist
      (odds ratio=0.83 [confidence interval ?CI?=0.74 to 0.94] p < 0.003) and
      physicians treating a high volume of acute myocardial infarction patients (odds
      ratio=0.89 [CI=0.80 to 0.99] p < 0.03) as independent predictors of lower in
      hospital mortality. Treatment by a cardiologist as compared to primary care
      physicians was also associated with a significantly lower length of stay for both
      medically treated patients (p < 0.01) and those undergoing revascularization (p <
      0.01). CONCLUSIONS: Treatment by a cardiologist is associated with approximately
      a 17% reduction in hospital mortality in acute myocardial infarction patients. In
      addition, patients of physicians treating a high volume of patients have
      approximately an 11% reduction in mortality. This has important implications for
      the optimal treatment of acute myocardial infarction in the current
      transformation of the health care delivery system.

PMID- 9768708
TI  - Prediction of short- and intermediate-term prognoses of patients with acute
      myocardial infarction using myocardial contrast echocardiography one day after
      recanalization.
AB  - OBJECTIVES: This study sought to determine whether microvascular integrity in the
      risk area (RA) for myocardial infarction (MI) one day after recanalization
      predicts the outcome in patients with first acute MI. BACKGROUND: Immediately
      after recanalization, microcirculation in the RA is modified by both hyperemic
      response and microvascular impairment. METHODS: Fifty consecutive patients who
      underwent serial myocardial contrast echocardiography before and one day after
      recanalization (day 2) were studied. All patients had a completely occluded
      lesion in the left anterior descending coronary artery alone, and underwent
      successful reperfusion therapy. The relative size of the initial RA (RA ratio)
      and peak gray scale ratio (PGSR) within the RA on day 2 were determined. Patients
      were followed for a median of 22 months to evaluate clinical outcome. RESULTS: On
      day 2, PGSR was a median of 0.46. Study patients were subdivided into two groups,
      group A of 24 patients with acceptable opacification (PGSR > 0.46 on day 2) and
      group B of 26 patients without it. Major cardiac events (cardiac death, nonfatal
      MI and repeat admission for congestive heart failure) were more frequently
      observed in group B (28% vs. 4%, Cox hazard ratio=8.5, p=0.05, 95% confidence
      interval [CI] 1.03 to 69.9). The median value of the RA ratio was 0.45. Patients
      (n=15) with RA ratio > 0.45 on day 1 and PGSR on day 2 < or = 0.46 exhibited a
      10.7-fold relative risk for major cardiac events (p=0.005, 95% CI 2.06 to 55.8)
      and a 3.69-fold relative risk for composite cardiac events (major cardiac events
      and target lesion revascularizations) after the initial intervention (p=0.004,
      95% CI 1.51 to 9.04). CONCLUSIONS: The assessment of both the size of the initial
      RA and microvascular integrity on day 2 enables precise determination of the
      efficacy of reperfusion therapy and prediction of the short- and intermediate
      term prognoses of patients with recanalized MI.

PMID- 9768709
TI  - Assessment of "microvascular no-reflow phenomenon" using technetium-99m
      macroaggregated albumin scintigraphy in patients with acute myocardial
      infarction.
AB  - OBJECTIVES: The aim of this study was the scintigraphic evaluation of clinical no
      reflow phenomenon. BACKGROUND: In patients with acute myocardial infarction, the
      relationship of the severity of reduction of microvascular reflow to the ischemia
      time or to the secondary extension of myocardial necrosis is poorly understood,
      and we accordingly conducted a scintigraphic evaluation of clinical no-reflow
      phenomenon. METHODS: The group studied consisted of 25 consecutive patients with
      their first acute myocardial infarction. After recanalization, each patient
      received intracoronary injections of technetium-99m macroaggregated albumin
      (MAA). RESULTS: Eight patients (32%) had absent tracer uptake (scintigraphic no
      reflow phenomenon). Fourteen patients showed absent or moderately reduced MAA
      uptake (group 1) and 11 showed slightly reduced or normal uptake (group 2). The
      time to recanalization was significantly longer in group 1 than in group 2
      (290.4+/-130.6 min vs. 1773+/-93.5 min; p=0.0238). In chronic phase, the thallium
      201 (TI-201) defect score index was significantly larger (p < 0.01) and regional
      ejection fraction was significantly lower (p < 0.01) in group 1 compared with
      corresponding values in group 2. No significant deterioration from acute phase to
      chronic phase in either TI-201 defect score index or regional ejection fraction
      was found in either group (two-way repeated measures analysis of variance).
      CONCLUSIONS: These findings suggest that scintigraphic noreflow phenomenon occurs
      in a subgroup of patients without angiographic no-reflow phenomenon, that the
      myocardial damage depends on the severity of microvascular damage and that
      prolonged ischemia time may increase the likelihood of "microvascular no-reflow
      phenomenon."

PMID- 9768710
TI  - Does acute improvement of endothelial dysfunction in coronary artery disease
      improve myocardial ischemia? A double-blind comparison of parenteral D- and L
      arginine.
AB  - OBJECTIVES: Parenteral L-arginine will improve myocardial ischemia in patients
      with obstructive coronary artery disease. BACKGROUND: Endothelial dysfunction
      causes coronary arterial constriction during stress, and L-arginine improves
      endothelial dysfunction. METHODS: Twenty-two patients with stable coronary artery
      disease and exercise-induced ST-segment depression underwent assessment of
      forearm endothelial function with acetylcholine and symptom-limited treadmill
      exercise testing during dextrose 5% infusion and after double-blind intravenous
      administration of L- and D-arginine (5 mg/kg/min) for 20 min. RESULTS: Forearm
      blood flow increased with both L- and D-arginine (33%+/-6% and 38%+/-7%,
      respectively, p < 0.001). Acetylcholine-mediated forearm vasodilation also
      improved with both L- and D-arginine (p < 0.0001). The magnitude of improvement
      was similar with both enantiomers and was observed in patients throughout the
      range of acetylcholine responses and cholesterol levels. Heart rate and blood
      pressure at rest and during each stage of exercise and exercise duration remained
      unchanged with L- and D-arginine compared to control. Ischemic threshold,
      measured either as the rate-pressure product or the duration of exercise at the
      onset of 1-mm ST-segment depression during exercise, also remained unchanged.
      Serum arginine, insulin and prolactin levels (p < 0.01) increased with both
      enantiomers. CONCLUSIONS: Parenteral arginine produces non-stereo-specific
      peripheral vasodilation and improves endothelium-dependent vasodilation in
      patients with stable coronary artery disease by stimulation of insulin-dependent
      nitric oxide release or by nonenzymatic nitric oxide generation. Despite enhanced
      endothelial function, there was no improvement in myocardial ischemia during
      stress with either enantiomer. Whether parenteral arginine will be of therapeutic
      benefit in acute coronary syndromes and oral arginine in myocardial ischemia
      needs to be studied further.

PMID- 9768711
TI  - Prognostic value of the amount of dysfunctional but viable myocardium in
      revascularized patients with coronary artery disease and left ventricular
      dysfunction. Investigators of this Multicenter Study.
AB  - OBJECTIVES: The purpose of our study was to assess the prognostic importance of
      the amount of dysfunctional but viable myocardium in revascularized patients with
      coronary artery disease (CAD) and left ventricular (LV) dysfunction. BACKGROUND:
      The amount of dysfunctional but viable myocardium predicts the functional
      improvement after revascularization and may offer more precise risk
      stratification of patients referred for bypass surgery or coronary angioplasty.
      METHODS: Two hundred and seventy-four consecutive patients with CAD and LV
      ejection fraction < or =40% underwent low-dose dobutamine echocardiography for
      viability assessment. One hundred and thirty-three of them were revascularized
      using either coronary artery bypass surgery (118 patients) or coronary
      angioplasty (15 patients) and entered this study. To quantify the amount of
      dysfunctional but viable myocardium, wall motion was scored using 16-segment
      model. The dysfunctional segments were defined as viable if they exhibited
      improvement in their thickening by at least 1 grade with dobutamine infusion. The
      patients were followed up for a mean period of 20+/-12 months (range, 2 to 48)
      for cardiac mortality and nonfatal cardiac events including myocardial
      infarction, unstable angina pectoris requiring hospitalization and
      hospitalization for heart failure. Standard follow-up echocardiography was
      performed 3 to 6 months after revascularization. RESULTS: Twenty-nine patients
      exhibited a large amount of dysfunctional but viable myocardium (> or =6
      segments, group A), 60 patients had a small amount of dysfunctional but viable
      myocardium (2 to 5 segments, group B) and 44 patients were found to have
      dysfunctional myocardium irreversibly damaged (group C). Similar
      prerevascularization LV ejection fractions of 35%+/-5%, 34%+/-4%, 36%+/-4% in
      groups A, B and C increased to 47%+/-6% (p < 0.01 vs. baseline, p < 0.01 vs.
      groups B and C), to 40%+/-5% (p < 0.01 vs. baseline) and to 37%+/-6% (p = NS vs
      baseline), respectively, after revascularization. The greatest functional
      improvement after revascularization in group A patients was accompanied by a
      lower rate of cardiac events during follow-up (2 vs. 18 in group B, p < 0.05, and
      vs. 17 in group C, p < 0.01) and better cardiac event-free survival according to
      Kaplan-Meier survival analysis (p < 0.05 vs. groups B and C, respectively).
      CONCLUSION: In revascularized patients with CAD and moderate or severe LV
      dysfunction, the presence of a large amount of dysfunctional but viable
      myocardium identifies patients with the best prognosis.

PMID- 9768712
TI  - Myocardial viability during dobutamine echocardiography predicts survival in
      patients with coronary artery disease and severe left ventricular systolic
      dysfunction.
AB  - OBJECTIVES: The purpose of this study was to assess whether the presence or
      absence of myocardial viability during dobutamine echocardiography (DE) predicts
      survival in patients with coronary artery disease (CAD) and severe left
      ventricular (LV) dysfunction. BACKGROUND: In patients with CAD, the presence of
      myocardial viability during DE identifies viable myocardium and predicts recovery
      of LV systolic function after revascularization. However, there is little data on
      the relation between myocardial viability and clinical outcome in patients with
      CAD and severe LV dysfunction. METHODS: We studied 318 patients with CAD and a LV
      ejection fraction (EF) < or =35% who underwent DE and were followed for 18+/-10
      months. Patients were classified into four groups. Group I (n=85) consisted of
      patients who had evidence of myocardial viability and subsequently underwent
      revascularization. Group II (n=119) consisted of patients with myocardial
      viability who did not undergo revascularization. Group III (n=30) consisted of
      patients who did not have myocardial viability and underwent revascularization.
      Finally, group IV (n=84) patients lacked myocardial viability and did not undergo
      revascularization. RESULTS: The four groups had similar baseline characteristics
      and rest LVEF. During follow-up there were 51 deaths (16%). The mortality rate
      was 6% in group I, 20% in group II, 17% in group III and 20% in group TV (p=0.01,
      group I vs. other groups). CONCLUSIONS: In patients with CAD and severe LV
      dysfunction who demonstrated myocardial viability during DE, revascularization
      improved survival compared with medical therapy.

PMID- 9768713
TI  - Attenuation-corrected 99mTc-tetrofosmin single-photon emission computed
      tomography in the detection of viable myocardium: comparison with positron
      emission tomography using 18F-fluorodeoxyglucose.
AB  - OBJECTIVES: The purpose of this study was to assess the efficacy of attenuation
      corrected (AC) technetium-99m (99mTc)-tetrofosmin single-photon emission computed
      tomography (SPECT) in detecting viable myocardium compared to 18F
      fluorodeoxyglucose (FDG) positron emission tomography (PET). BACKGROUND: The role
      of 99mTc-labeled perfusion tracers in the assessment of myocardial viability
      remains controversial. Attenuation artifacts affect the diagnostic accuracy of
      SPECT images. METHODS: Twenty-four patients with coronary artery disease (mean
      left ventricular ejection fraction 30%) underwent resting 99mTc-tetrofosmin SPECT
      and FDG PET imaging. Both AC and non-attenuation-corrected (NC) SPECT images were
      generated. RESULTS: Using a 50% threshold for viability by FDG PET, the
      percentage of concordant segments of viability between 99mTc-tetrofosmin and FDG
      on the patient basis increased from 79.8%+/-14.0% (mean+/-SD) on the NC images to
      90.8%+/-10.6% on the AC images (p=0.002). The percentage of 99mTc-tetrofosmin
      defect segments within PET-viable segments, an estimate for the degree of
      underestimation of viability, decreased from 19.8%+/-15.2% on the NC images to
      9.7%+/-12.6% on the AC images (p=0.01). Similar results were obtained when a 60%
      threshold was used to define viability by FDG PET. When the anterior-lateral and
      inferior-septal regions were separately analyzed, the effect of attenuation
      correction was significant only in the inferior-septal region. CONCLUSIONS: The
      results indicate that AC 99mTc-tetrofosmin SPECT improves the detection of viable
      myocardium mainly by decreasing the underestimation of viability particularly in
      the inferior-septal region, although some underestimation/overestimation of
      viability may still occur even with attenuation correction.

PMID- 9768714
TI  - Prognostic value of congestive heart failure history in patients undergoing
      percutaneous coronary interventions.
AB  - OBJECTIVES: We sought to determine the prognostic significance of a history of
      congestive heart failure above that provided by baseline ejection fraction in
      patients undergoing percutaneous coronary interventions. BACKGROUND: Left
      ventricular function is a known predictor of survival in patients with coronary
      artery disease, as is a history of congestive heart failure. The contribution of
      heart failure history independent of left ventricular function is unknown.
      METHODS: Data were pooled from four interventional trials and the Duke University
      database. The combined dataset included 5,260 patients undergoing percutaneous
      interventions, 334 with and 4,926 without a history of heart failure. Patients
      were defined by the treating physician as having a clinical history of heart
      failure at the time of enrollment. RESULTS: The 30-day and 6-month mortality were
      higher in patients with a clinical history of congestive heart failure than in
      those without such a history (2% vs. <1%, p=0.002 at 30 days, 5% vs. 1%, p=0.001
      at 6 months). Heart failure history did not influence the incidence of myocardial
      infarction, use of angioplasty or the use of bypass surgery during follow-up.
      Multivariable analysis revealed that heart failure history added significantly to
      ejection fraction in predicting intermediate-term (6-month) mortality (p=0.01).
      Stepwise logistic regression also revealed heart failure history to be an
      independent predictor of 6-month mortality (odds risk 1.9, 95% confidence
      interval 1.1 to 3.5). CONCLUSIONS: A clinical history of congestive heart failure
      is associated with increased early and intermediate-term mortality in patients
      undergoing percutaneous revascularization. Congestive heart failure history
      appears to provide prognostic information independent of that available from a
      patient's left ventricular function. These findings suggest that patients with a
      clinical history of congestive heart failure who undergo a percutaneous
      intervention should be closely monitored, especially those with the lowest
      ejection fractions.

PMID- 9768715
TI  - Prevalence and significance of nonsustained ventricular tachycardia in patients
      with premature ventricular contractions and heart failure treated with
      vasodilator therapy. Department of Veterans Affairs CHF STAT Investigators.
AB  - OBJECTIVES: This study sought to determine the prevalence and significance of
      nonsustained ventricular tachycardia (NSVT) in patients with premature
      ventricular contractions (PVCs) and heart failure treated with vasodilator
      therapy. BACKGROUND: Heart failure patients with ventricular arrhythmia and NSVT
      have a significantly increased risk of premature cardiac death. Recently there
      has been the question of whether these arrhythmias are expressions of a severely
      compromised ventricle or are they independent risk factors. We, therefore,
      determined the prevalence and significance of NSVT in patients with PVCs and
      heart failure and on vasodilator therapy. METHODS: Twenty-four hour ambulatory
      recordings were done at randomization, at 2 weeks, at months 1, 3, 6, 9 and 12
      and then every 6 months in 674 patients with heart failure and on vasodilator
      therapy. The median period of follow-up was 45 months (range 0 to 54). RESULTS:
      Nonsustained ventricular tachycardia was present in 80% of all patients. Patients
      without (group 1) and with (group 2) NSVT were balanced for variables: age,
      etiology of heart disease, New York Heart Association (NYHA) functional class,
      use of amiodarone and diuretics and left ventricular diameter by echocardiogram.
      However, group 1 patients had significantly less beta-adrenergic blocking agent
      use and higher ejection fraction (EF) (p < 0.002 and p < 0.001, respectively).
      Survival analysis for all deaths showed a greater risk of death among group 2
      patients (p=0.01). Similarly, sudden death was increased in group 2 patients
      (p=0.02, risk ratio 1.8). After adjusting for the above variables, only EF
      (p=0.001) and NYHA class (p=0.01) were shown to be independent predictors of
      survival. Nonsustained ventricular tachycardia showed a trend (p=0.07) as an
      independent predictor for all-cause mortality but not for sudden death. Only EF
      was an independent predictor for sudden death. CONCLUSIONS: Nonsustained
      ventricular tachycardia is frequently seen in patients with heart failure and may
      be associated with worsened survival by univariate analysis. However, after
      adjusting other variables, especially for EF, NSVT was not an independent
      predictor of all-cause mortality or sudden death. These results have serious
      implications in that suppression of these arrhythmias may not improve survival.

PMID- 9768716
TI  - Right ventricular ejection fraction is an independent predictor of survival in
      patients with moderate heart failure.
AB  - OBJECTIVES: We sought to study the relationship between survival and right
      ventricular ejection fraction (RVEF) in a subgroup of patients with moderate
      congestive heart failure (CHF). BACKGROUND: It has been demonstrated that RVEF is
      an independent predictor of survival in patients with advanced CHF. METHODS:
      Cardiopulmonary exercise testing and radionuclide angiography (to determine right
      and left ventricular ejection fraction) were prospectively performed in 205
      consecutive patients with moderate CHF (140 patients in New York Heart
      Association [NYHA] class II, 65 in class III). RESULTS: Left ventricular ejection
      fraction was 29.3%+/-10.1%, RVEF was 37.5%+/-14.6% and peak oxygen consumption
      (VO2) was 16.2+/-5.4 ml/min/kg (60.2%+/-19% of maximal predicted VO2). After a
      median follow-up period of 755 days, there were 44 cardiac-related deaths, 3
      deaths from noncardiac causes and 15 transplantations of whom 2 were urgent; 1
      patient was lost to follow-up. Multivariate analysis showed that three variables
      NYHA classification, percent of maximal predicted VO2 and RVEF-were independent
      predictors of both survival and event-free cardiac survival. Left ventricular
      ejection fraction and peak VO2 normalized to body weight had no predictive value.
      The event-free survival rates from cardiovascular mortality and urgent
      transplantation at 1 year were 80%, 90% and 95% in patients with an RVEF <25%,
      with a RVEF > or =25% and <35% and with a RVEF > or =35%, respectively. At 2
      years, survival rates were 59%, 77% and 93% in the same subgroups, respectively.
      CONCLUSIONS: In addition to the NYHA classification and to the percent of maximal
      predicted VO2, RVEF is an independent predictor of survival in patients with
      moderate CHF.

PMID- 9768717
TI  - Expression, activity and functional significance of inducible nitric oxide
      synthase in the failing human heart.
AB  - OBJECTIVES: The study was designed to evaluate the functional impact of nitric
      oxide (NO) generation within the myocardium on cardiac contraction in the failing
      human heart. BACKGROUND: Heart failure is associated with activation of cytokines
      and expression of inducible nitric oxide synthase (NOS II), which generates NO
      from L-arginine. Nitric oxide has been shown to modulate myocardial performance,
      raising the possibility that cardiac generation of NO by NOS II modulates cardiac
      contraction in the failing human heart. METHODS: Left ventricular (LV) tissue of
      24 patients with end-stage heart failure was obtained during cardiac
      transplantation. Gene expression of NOS II and endothelial NO-synthase (NOS III)
      was quantified by competitive reverse transcription-polymerase chain reaction and
      compared to tissues of five nonfailing donor hearts. Nitric oxide synthase II
      activity was determined by citrulline assay and related to changes in force of
      contraction induced by the beta-adrenergic agonist isoproterenol, NO-donors
      and/or N-mono-methyl-L-arginine (L-NMMA), an inhibitor of NOS. RESULTS: While NOS
      III mRNA was reduced in failing hearts, NOS II mRNA was increased in failing LV
      tissue and correlated with NOS II activity. High NOS II activity was associated
      with early relaxation and impaired responsiveness to beta-adrenergic stimulation,
      that is, the inotropic response to isoproterenol in failing hearts was inversely
      related to NOS II activity (r=0.61, p < 0.005). Nitric oxide donors or L-NMMA did
      not affect myocardial performance in failing hearts at baseline. However, L-NMMA
      enhanced the positive inotropic response to beta-adrenergic stimulation in
      failing hearts with high NOS II activity. Nitric oxide donors attenuated the
      isoproterenol-induced increase in force of contraction of failing hearts.
      CONCLUSIONS: Cardiac production of NO by NOS II attenuates the positive inotropic
      effects of beta-adrenergic stimulation and hastens relaxation in failing human
      hearts.

PMID- 9768718
TI  - Inducible nitric oxide synthase in skeletal muscle of patients with chronic heart
      failure.
AB  - OBJECTIVES: The expression and localization of inducible nitric oxide (NO)
      synthase (NOS II) was evaluated as a source of NO which has been shown to affect
      muscle contraction. BACKGROUND: Advanced stages of chronic heart failure are
      associated with systemic activation of cytokines which have been shown to
      stimulate the expression of NOS II in various cell types, including myocytes. We
      hypothesized that systemic cytokine activation could lead to expression of NOS II
      in skeletal muscle of patients with chronic heart failure. METHODS: Skeletal
      muscle specimens were obtained by percutaneous needle biopsy in six normal
      volunteers and eight patients with heart failure (New York Heart Association
      class III). Electron microscopy immunocytochemistry (immunogold labeling) with
      specific anti-NOS antibodies was utilized to elucidate the intracellular
      localization of NOS II and neuronal NO synthase (NOS I) in myocytes of skeletal
      muscle. Reverse transcriptase, competitive polymerase chain reaction (PCR) was
      applied to quantify NOS II mRNA in skeletal muscle. RESULTS: Inducible nitric
      oxide synthase was readily expressed in the cytosol of skeletal muscle myocytes;
      NOS I expression was sparse. Polymerase chain reaction results indicated that NOS
      II gene expression is increased in patients with chronic heart failure.
      CONCLUSIONS: Inducible NO synthase is expressed in human skeletal muscle and its
      gene expression is increased in patients with severe heart failure. Given the
      experimental evidence that NO can attenuate contractile performance of skeletal
      muscle and can mediate muscle wasting, an increased local production of NO in
      skeletal muscle by NOS II may have important implications for patients with
      severe heart failure.

PMID- 9768719
TI  - Operator volume and outcome of patients undergoing coronary stent placement.
AB  - OBJECTIVES: The aim of this study was to assess the relation between operator
      experience in coronary stent placement procedures and the clinical outcome of
      patients. BACKGROUND: The results of coronary balloon angioplasty are closely
      related to the experience of the operator performing the procedure. Data on the
      effect of operator experience on the results after coronary stent placement are
      missing. METHODS: The study included 3,409 consecutive patients undergoing
      coronary stent placement for the management of coronary artery disease. A
      composite end point of cardiac death, myocardial infarction and aortocoronary
      bypass surgery during the first 30 days after the intervention, was the primary
      end point and the procedural failure was the secondary end point of the study.
      RESULTS: Adverse clinical outcome occurred in 2.99% of the 3,409 patients
      undergoing coronary stent placement. Procedural failure was recorded in 2.08% of
      the patients. Operator volumes above 483 procedures were associated with a risk
      adjusted adverse outcome rate of 1.70%+/-1.28%, which is significantly lower than
      the overall rate of 2.99%. Operator yearly volumes of under 90 procedures were
      associated with a risk-adjusted adverse outcome rate of 4.59%+/-1.17%, which is
      significantly higher than the overall rate of 2.99%. The operator experience was
      an independent predictor even after adjusting for the effect of other risk
      factors. The analysis demonstrated that an experience of at least 100 procedures
      is required to obtain better outcome even in patients with simple coronary
      lesions and that operators should perform at least 70 procedures annually to
      expect a better outcome in patients with both simple and complex coronary
      lesions. CONCLUSIONS: Operator experience is a significant and independent
      predictor of the outcome of patients undergoing coronary stent placement. An
      experience of at least 100 procedures and an annual volume of at least 70
      procedures are required to ensure a significantly better outcome after coronary
      stent implantation.

PMID- 9768720
TI  - Stents: expanding the case for volume minimums in interventional cardiology.

PMID- 9768721
TI  - Balloon angioplasty for the treatment of coronary in-stent restenosis: immediate
      results and 6-month angiographic recurrent restenosis rate.
AB  - OBJECTIVES: The purpose of this prospective study was to evaluate the immediate
      results and the 6-month angiographic recurrent restenosis rate after balloon
      angioplasty for in-stent restenosis. BACKGROUND: Despite excellent immediate and
      mid-term results, 20% to 30% of patients with coronary stent implantation will
      present an angiographic restenosis and may require additional treatment. The
      optimal treatment for in-stent restenosis is still unclear. METHODS: Quantitative
      coronary angiography (QCA) analyses were performed before and after stent
      implantation, before and after balloon angioplasty for in-stent restenosis and on
      a 6-month systematic coronary angiogram to assess the recurrent angiographic
      restenosis rate. RESULTS: Balloon angioplasty was performed in 52 patients
      presenting in-stent restenosis. In-stent restenosis was either diffuse (> or =10
      mm) inside the stent (71%) or focal (29%). Mean stent length was 16+/-7 mm.
      Balloon diameter of 2.98+/-0.37 mm and maximal inflation pressure of 10+/-3 atm
      were used for balloon angioplasty. Angiographic success rate was 100% without any
      complication. Acute gain was lower after balloon angioplasty for in-stent
      restenosis than after stent implantation: 1.19+/-0.60 mm vs. 1.75+/-0.68 mm
      (p=0.0002). At 6-month follow-up, 60% of patients were asymptomatic and no
      patient died. Eighteen patients (35%) had repeat target vessel revascularization.
      Angiographic restenosis rate was 54%. Recurrent restenosis rate was higher when
      in-stent restenosis was diffuse: 63% vs. 31% when focal, p=0.046. CONCLUSIONS:
      Although balloon angioplasty for in-stent restenosis can be safely and
      successfully performed, it leads to less immediate stenosis improvement than at
      time of stent implantation and carries a high recurrent angiographic restenosis
      rate at 6 months, in particular in diffuse in-stent restenosis lesions.

PMID- 9768722
TI  - Relations between cardiac and vascular structure in patients with primary and
      secondary hypertension.
AB  - BACKGROUND: Data on cardiac and vascular structure in secondary hypertension are
      generally scarce, and no data on the interrelations between cardiac mass and
      structural characteristics of the vessel wall, both in large and in small
      resistance arteries, are presently available. OBJECTIVES: The aim of this study
      was to investigate the relation between structural changes in subcutaneous small
      arteries, left ventricular mass and wall thickness of the common carotid artery
      in patients with primary and secondary hypertension. METHODS: Seventy-four
      subjects were included in the study: 11 patients with pheochromocytoma, 14 with
      primary aldosteronism (PA), 19 with renovascular hypertension (RVH), 18 with
      essential hypertension (EH) and 12 normotensive (NT) control subjects. All
      subjects were submitted to a biopsy of subcutaneous fat. Morphologic
      characteristics of subcutaneous small resistance arteries (relaxed diameter <300
      microm) were directly evaluated using a micromyographic technique. All subjects
      were submitted to calculation of left ventricular mass index (LVMI) and common
      carotid artery intima-media thickness (CCIMT), using ultrasound technique.
      RESULTS: The correlation coefficients between the media to lumen ratio in
      subcutaneous small arteries (M/L) and LVMI or between M/L and CCIMT were closer
      in RVH than in pheochromocytoma, EH or NT; in PA the correlation coefficients
      were slightly less close than those in RVH. An excess prevalence of carotid
      plaques in RVH was observed. CONCLUSIONS: A close relation between small
      resistance artery morphology and cardiac or carotid artery structure may be
      observed in those hypertensive patients in whom the renin-angiotensin-aldosterone
      system is activated. In constrast, in NT, EH and pheochromocytoma no significant
      correlation between M/L and LVMI or CCIMT was observed.

PMID- 9768723
TI  - The effects of New York's bypass surgery provider profiling on access to care and
      patient outcomes in the elderly.
AB  - OBJECTIVE: The aim of this study was to examine the effects of provider profiling
      on bypass surgery access and outcomes in elderly patients in New York.
      BACKGROUND: Since 1989, New York (NY) has compiled provider-specific bypass
      surgery mortality reports. While some have proposed that "provider profiling" has
      led to lower surgical mortality rates, critics have suggested that such programs
      lower in-state procedural access (increasing out-of-state transfers) without
      improving patient outcomes. METHODS: Using national Medicare data, we examined
      trends in the percentages of NY residents aged 65 years or older receiving out-of
      state bypass surgery between 1987 and 1992 (before and after program initiation).
      We also examined in-state procedure use among elderly myocardial infarction
      patients during this period. Finally, we compared trends in surgical outcomes in
      NY Medicare patients with those for the rest of the nation. RESULTS: Between 1987
      and 1992, the percentage of NY residents receiving bypass out-of-state actually
      declined (from 12.5% to 11.3%, p < 0.01 for trend). An elderly patient's
      likelihood for bypass following myocardial infarction in NY increased
      significantly since the program's initiation. Between 1987 and 1992, unadjusted
      30-day mortality rates following bypass declined by 33% in NY Medicare patients
      compared with a 19% decline nationwide (p < 0.001). As a result of this
      improvement, NY had the lowest risk-adjusted bypass mortality rate of any state
      in 1992. CONCLUSIONS: We found no evidence that NY's provider profiling limited
      procedure access in NY's elderly or increased out-of-state transfers. Despite an
      increasing preoperative risk profile, procedural outcomes in NY improved
      significantly faster than the national average.

PMID- 9768724
TI  - How do we know how well we are doing?

PMID- 9768725
TI  - Hemodynamic performance of cryopreserved aortic homograft valves during midterm
      follow-up.
AB  - OBJECTIVES: The aim of this prospective study of adult patients operated with a
      cryopreserved aortic homograft was to use serial echocardiographic data to
      evaluate the postoperative hemodynamic performance of these valves. BACKGROUND:
      Only limited data on hemodynamic performance of aortic homografts at rest and
      during exercise are available. Controversy also exists regarding incidence and
      progression of aortic regurgitation (AR). METHODS: Fifty-nine patients aged 39-86
      years who received an aortic homograft (median size 21 mm) implanted with
      subcoronary technique were studied with serial Doppler-echocardiography (D-E). In
      31 of these patients, D-E also was performed during supine exercise. RESULTS:
      Overall survival was 100% during a median follow-up of 28 months (range 4-54).
      During follow-up AR grade II or more was detected in 25% of the patients with an
      increasing time-related risk of developing AR. Maximum and mean pressure
      differences at 7 months follow-up calculated with the short form of the Bernoulli
      equation were 11.4 (4.6) and 5.5 (2.1) mm Hg, respectively. During supine
      exercise that increased cardiac output 72%, maximum pressure difference increased
      from 11.9 (5.2) to 18.5 (9.5) mm Hg. CONCLUSIONS: The aortic homograft valve
      shows low pressure differences at rest and during exercise, but AR grade I or II
      is often seen during follow-up. As AR progresses with time we stress the
      importance of echocardiographic follow-up of patients with aortic homografts.

PMID- 9768726
TI  - Retrograde nontransseptal balloon mitral valvuloplasty: immediate results and
      intermediate long-term outcome in 441 cases--a multicenter experience.
AB  - OBJECTIVES: Our aim was to present the immediate and intermediate long-term
      results of the application of retrograde nontransseptal balloon mitral
      valvuloplasty (RNBMV) in four cooperating centers from Greece and India.
      BACKGROUND: RNBMV is a purely transarterial method of balloon valvuloplasty,
      developed with the aim to avoid complications associated with transseptal
      catheterization. Only single-center experience with RNBMV has been previously
      reported. METHODS: The procedure was attempted in 441 patients with symptomatic
      mitral stenosis (320 women, 121 men, mean age [+/-SD] 44+/-11 years, mean
      echocardiographic score [+/-SD] 7.7+/-2.0) from 1988 to 1996. Three hundred
      eighty-five patients with successful immediate outcome were followed clinically
      for a mean [+/-SD] of 3.5+/-1.9 (range, 0.5-9.1) years. RESULTS: A technically
      successful procedure was achieved in 388 (88%) cases. The echocardiographic score
      (p < 0.001), male gender (p=0.005), preprocedural mitral regurgitation (p=0.007)
      and previous surgical commissurotomy (p=0.029) were unfavorable predictors of
      immediate outcome. Complications included death (0.2%), severe mitral
      regurgitation (3.4%) and injury of the femoral artery (1.1%). Event-free (freedom
      from cardiac death, mitral valve surgery, repeat valvuloplasty and NYHA class >
      II symptoms) survival rates (+/-SEM) were 100%, 96.9+/-0.9%, 89.8+/-1.9% and
      75.5+/-5.5% at 1, 2, 4 and 9 years, respectively. The echocardiographic score (p
      < 0.001), NYHA class (p=0.008) and postprocedural mitral valve area (p=0.009)
      were significant independent predictors of intermediate long-term outcome.
      CONCLUSIONS: Multicenter experience indicates that RNBMV is a safe and effective
      technique for the treatment of symptomatic mitral stenosis. As with the
      transseptal approach, patients with favorable mitral valve anatomy derive the
      greatest immediate and intermediate long-term benefit from this procedure.

PMID- 9768727
TI  - Echocardiographic and biochemical evaluation of the development and progression
      of carcinoid heart disease.
AB  - OBJECTIVES: To study the applicability of a newly developed echocardiographic
      scoring system in the assessment of carcinoid valvular heart disease. BACKGROUND:
      We investigated prospectively the development, progression and regression of
      carcinoid valvular heart disease in patients with carcinoid syndrome by serial
      echocardiography, correlating these features with urinary 5-HIAA levels and
      clinical data collected during therapy with somatostatin analog. METHODS: Twenty
      three patients with carcinoid syndrome underwent serial echocardiographic
      examinations. An echocardiographic carcinoid valvular heart disease (CVHD) %
      score was determined from points assigned for tricuspid and pulmonary valve
      structure and function. RESULTS: Fifteen patients had no CVHD at study entry
      (group 1), while 8 patients had findings of CVHD (group 2). Five patients in
      group q developed new CVHD (1B), while one demonstrated progression of CVHD (2B).
      The remaining patients did not develop (1A) or had no progression of CVHD (2B).
      Despite major declines in 5-HIAA levels during therapy in most patients, CVHD did
      not regress. There were significantly lower levels of median baseline 5-HIAA
      (98.8 vs. 256 mg/24 h), posttreatment 5-HIAA (50.3 vs. 324 mg/24 h) and
      posttreatment 5-HIAA time integral (37.3 vs. 192 g/24 h* days) in group A vs. B
      (p < 0.05). However, only posttreatment 5-HIAA levels independently predicted the
      development or progression of CVHD by multiple step-wise regression analysis (p <
      0.005), with a threshold observed in the 100 mg/24 h range. CONCLUSIONS: We
      designed a new echocardiographic scoring system to evaluate CVHD. Correlating
      echocardiographic scores with biochemical and clinical markers showed that only
      posttreatment 5-HIAA levels independently predicted the development or
      progression of CVHD. This study strengthens the association between serotonin
      secretion and CVHD, as well as introducing a new technique for serial follow-up
      of these patients.

PMID- 9768728
TI  - Tricuspid valve surgery and intraoperative echocardiography: factors affecting
      survival, clinical outcome, and echocardiographic success.
AB  - BACKGROUND: The impact of echocardiographic-guided treatment on outcome after
      tricuspid valve (TV) surgery is not well defined. OBJECTIVES: The purpose of this
      study was to determine clinical and echocardiographic factors associated with
      adverse outcomes after TV surgery and determine the role of intraoperative echo
      (IOE) in facilitating successful outcomes after TV surgery. METHODS: Four hundred
      and one patients (279 females, mean age 60 years) underwent TV surgery and other
      concomitant cardiac surgery at a single institution and were followed clinically
      and by echocardiography during a 10-year period. RESULTS: Decreased survival
      after TV surgery was associated with: preoperative increased New York Heart
      Association (NYHA) functional classification (relative risk [RR]=2.02), increased
      left ventricular dysfunction by echocardiography (RR=1.28), and use of a TV
      replacement strategy (RR=2.92). Decreased event-free survival after TV surgery
      was associated with concomitant coronary artery bypass grafting (RR=2.97). Late
      echocardiographic failure (3 to 4+ tricuspid valve regurgitation [TR]) after TV
      surgery was associated with increased severity of TR on preoperative
      echocardiogram (odds ratio [OR]=1.91). Decreased late echocardiographic failure
      after TV surgery was associated with the use of a TV annuloplasty ring with a
      repair strategy (OR=0.40). The surgical plan was altered at the time of surgery
      to insure a successful outcome in 32 (10%) of 335 patients based on IOE findings.
      CONCLUSIONS: Adverse outcomes after TV surgery can be predicted by several
      preoperative clinical and echocardiographic variables. IOE is useful in improving
      immediate, but not late, outcomes after TV surgery.

PMID- 9768729
TI  - Application of the proximal flow convergence method to calculate the effective
      regurgitant orifice area in aortic regurgitation.
AB  - OBJECTIVES: We sought to determine the reliability of the proximal isovelocity
      surface area (PISA) method for calculation of effective regurgitant orifice (ERO)
      of aortic regurgitation (AR). BACKGROUND: The ERO area can be calculated by the
      PISA method, but this method has not been validated in AR. METHODS: ERO
      calculation by the PISA method was undertaken prospectively in 71 consecutive
      patients with isolated AR and achieved in 64 and compared with two simultaneous
      reference methods (quantitative Doppler and quantitative two-dimensional
      echocardiography). In addition, this method was compared with angiography in 12
      patients, with surgical assessment in 18 patients and with ventricular volumes in
      all patients. RESULTS: Good correlations between PISA and reference methods were
      obtained (both r=0.90, both p < 0.0001), but a trend toward underestimation of
      the ERO by the PISA method was noted (24+/-19 vs. 26+/-22 mm2 and 27+/-23 mm2,
      respectively, both p=0.04). However, this trend was confined to five patients
      with an obtuse flow convergence angle (>220 degrees), and on multivariate
      analysis this variable was the only independent determinant of underestimation of
      the ERO. In contrast, in 59 patients with a flat flow convergence (< or =220
      degrees ), the PISA method, in comparison with reference methods, showed
      excellent correlations, with a narrow standard error of the estimate (r=0.95, SEE
      5.4 mm2, and r=0.95, SEE 5.8 mm2; all p < 0.0001) and no trend toward
      underestimation (22+/-18 vs. 23+/-16 mm2, p=0.44, and vs. 23+/-18 mm2, p=0.34).
      CONCLUSIONS: In patients with AR, the PISA method can be used to measure the ERO
      with reasonable feasibility. Underestimation of the ERO by PISA may occur in
      patients with an obtuse flow convergence angle. However, in most patients with
      appropriate flow convergence, PISA provides reliable measurement of the ERO of
      AR.

PMID- 9768730
TI  - Transient sinus node dysfunction after the Cox-maze III procedure in patients
      with organic heart disease and chronic fixed atrial fibrillation.
AB  - OBJECTIVES: This prospective study examined types, frequency and time dependency
      of the electrophysiologic manifestation of the sinus node dysfunction after the
      Cox-maze III procedure--the technique of choice for the management of medically
      refractory atrial fibrillation-in patients with organic heart disease, chronic
      fixed atrial fibrillation and no preoperatively overt dysfunction of the sinus
      node. BACKGROUND: The original maze procedure was modified twice in order to
      reduce the high incidence of the sinus node inability to generate an appropriate
      sinus tachycardia in response to maximal exercise, and occasional left atrial
      dysfunction. Despite these modifications, postoperative disturbance of sinus node
      function can be frequently observed. METHODS: In 15 adult patients, standard
      electrocardiogram, 24-h Holter monitoring, power spectral analysis of heart
      variability, exercise testing, Valsalva maneuver and rapid positional changes
      were performed 3, 6 and 12 months after the Cox-maze III procedure and mitral
      valve surgery or closure of atrial septal defect. RESULTS: Electrocardiographic
      manifestations of sinus node dysfunction were identified in 12 patients at 3
      months, in 6 patients at 6 months, and in 0 patients at 12 months after surgery.
      The heart rate response to exercise during the first 6 months was reduced in the
      maze group and became fully normal at 12 months. Power spectral analysis of heart
      rate variability showed very low power values at 1 month with inhibited cardiac
      autonomic activity and no response on sympathetic stress. A potential of recovery
      of cardiac autonomic activity was documented 12 months after surgery.
      CONCLUSIONS: The manifestations of sinus node dysfunction following the Cox-maze
      III procedure were time dependent and their frequency and intensity progressively
      decreased and disappeared within 12 months after surgery.

PMID- 9768731
TI  - Catheter ablation of atrioatrial conduction as a cure for atrial arrhythmia after
      orthotopic heart transplantation.
AB  - OBJECTIVES: We present three patients in whom atrial arrhythmia was treated by
      ablation of electrical conduction across a surgical suture line. BACKGROUND:
      Conduction across the suture line separating the donor and native right atria has
      recently been described after orthotopic heart transplantation. METHODS: Mapping
      and pacing of both grafted and recipient right atrium was performed to assess the
      relation between both atria and its relevance to clinical arrhythmia, prior to
      successful radiofrequency at the site of electrical communication. RESULTS: In
      cases 1 and 3, atrioatrial conduction was bidirectional. In both, two types of P
      waves were observed during sinus rhythm. In case 2, conduction from the recipient
      to the grafted atrium yielded a very particular surface ECG pattern of atrial
      extrasystole. The block being unidirectional, the recipient atrial sinus rhythm
      was not perturbed and behaved like an atrial parasystole. Ablation was performed
      during sinus rhythm in case 1, recipient right atrial pacing in case 2 and
      grafted right atrial pacing in case 3 at the site with the shortest conduction
      time to the other tissue. At the successful ablation site multiple component
      potentials were recorded. Respectively, 1, 4 and 2 radiofrequency pulses were
      followed by total atrioatrial conduction interruption. No tachycardia could be
      induced at the end of the procedure and late follow-up was event free.
      CONCLUSIONS: The existence of arrhythmogenic atrioatrial conduction should be
      taken into account when evaluating atrial arrhythmias in the transplanted heart
      because it is potentially curable by radiofrequency catheter ablation.

PMID- 9768732
TI  - Cardiac death and stored electrograms in patients with third-generation
      implantable cardioverter-defibrillators.
AB  - OBJECTIVES: We sought to utilize terminal stored intracardiac electrograms (EGMs)
      to study the electrophysiologic events that accompany mortality in patients with
      third-generation implantable cardioverter-defibrillators (ICDs). BACKGROUND:
      Despite their ability to effectively terminate ventricular tachyarrhythmias,
      cardiac mortality in patients with ICDs remains high. The mechanisms and modes of
      death in these patients are not well understood. METHODS: We retrospectively
      analyzed clinical data and stored EGMs from patients enrolled in the clinical
      trial of the Ventritex Cadence ICD. Of the 1,729 patients 119 died during 6 years
      of follow-up. The final recorded EGM was reviewed. Postimplant EGMs as well as 50
      control EGMs were used to define normal EGM characteristics. RESULTS: There were
      36 noncardiac deaths (30%) and 83 cardiac deaths (70%). Of the cardiac deaths, 55
      (66%) were nonsudden and 28 (34%) were sudden. When cardiac deaths were analyzed,
      46 (55%) had no stored EGMs within 1 h of death, implying that the deaths were
      not directly related to tachyarrhythmias. In 37 cardiac deaths (18 nonsudden, 19
      sudden), stored EGMs were present within 1 h of death. In these 37 deaths, the
      final EGM recorded was wide (>158 ms) in 33 (89%). Wide EGMs were interpreted as
      ventricular tachycardia in 27 and ventricular fibrillation in 6. In 13 of the 33
      patients (39%) with wide EGMs, therapy was not delivered by the ICD, as it
      incorrectly detected a spontaneous termination of the arrhythmia. EGMs were
      significantly wider if recorded within 1 h, as compared with those recorded from
      1 to 48 h before death (261+/-124 vs. 181+/-93 ms, p=0.04). CONCLUSIONS: Only 37
      patients (31%) who died after placement of an ICD had a stored EGM within 1 h of
      the time of death, suggesting that the majority of deaths (69%) were not the
      immediate result of a tachyarrhythmia. When EGMs were recorded, they were wide in
      89% of patients. These wide EGMs most likely represent intracardiac recordings of
      electromechanical dissociation. Thus, of the 119 deaths, 112 (94%) were not the
      immediate result of a tachyarrhythmia.

PMID- 9768733
TI  - Amiodarone reduces transmural heterogeneity of repolarization in the human heart.
AB  - OBJECTIVES: The present work was designed to test the effects of amiodarone
      therapy on action potential characteristics of the three cell types observed in
      human left ventricular preparations. BACKGROUND: The electrophysiologic basis for
      amiodarone's exceptional antiarrhythmic efficacy and low proarrhythmic profile
      remains unclear. METHODS: We used standard microelectrode techniques to
      investigate the effects of chronic amiodarone therapy on transmembrane activity
      of the three predominant cellular subtypes (epicardial, midmyocardial [M] and
      endocardial cells) spanning the human left ventricle in hearts explanted from
      normal, heart failure and amiodarone-treated heart failure patients. RESULTS:
      Tissues isolated from the ventricles of heart failure patients receiving chronic
      amiodarone therapy displayed M cell action potential duration (404+/-12 ms)
      significantly briefer (p < 0.05) than that recorded in tissues isolated from
      normal hearts (439+/-22 ms) or from heart failure patients not treated with
      amiodarone (449+/-18 ms). Endocardial cells from amiodarone-treated heart failure
      patients displayed longer (p < 0.05) action potential duration (363+/-10 ms) than
      endocardial cells isolated from normal hearts (330+/-6 ms). As a consequence, the
      heterogeneity of ventricular repolarization in tissues from patients treated with
      amiodarone was considerably smaller than in the two other groups, especially at
      long pacing cycle lengths. CONCLUSIONS: These findings may explain, at least in
      part, the reduction of ventricular repolarization dispersion and the lower
      incidence of torsade de pointes observed with chronic amiodarone therapy as
      compared with other class III agents.

PMID- 9768734
TI  - Inhaled nitric oxide in primary pulmonary hypertension: a safe and effective
      agent for predicting response to nifedipine.
AB  - OBJECTIVES: The purpose of this study was to assess the utility of inhaled nitric
      oxide (NO), a selective pulmonary vasodilator, for predicting the safety and
      acute hemodynamic response to high-dose oral nifedipine in primary pulmonary
      hypertension (PPH). BACKGROUND: A significant decrease in pulmonary vascular
      resistance with an oral nifedipine challenge is predictive of an improved
      prognosis, and potential clinical efficacy in PPH. However, the required
      nifedipine trial carries significant first-dose risk of hypotension. While
      inhaled NO has been recommended for assessing pulmonary vasodilator reserve in
      PPH, it is not known whether it predicts the response to nifedipine. METHODS:
      Seventeen patients with PPH undergoing a nifedipine trial were assessed for
      hemodynamic response to inhaled NO at 80 parts per million for 5 minutes. The
      nifedipine trial consisted of 20 mg of nifedipine hourly for 8 hours unless
      limited by hypotension or intolerable side effects. Patients were classified as
      responders and nonresponders with positive response defined as > or =20%
      reduction in mean pulmonary artery pressure (mPA) or pulmonary vascular
      resistance (PVR) with the vasodilator administration. RESULTS: NO was safely
      administered to all participants. Seven of 17 (41.2%) responded to NO, and 8 of
      the 17 to nifedipine (47.1%). Nifedipine was safely administered in 14 of the 17.
      Three suffered either mild or severe hypotension, including one death. All NO
      responders also responded to nifedipine, and 9 of the 10 NO nonresponders were
      nifedipine nonresponders, representing a sensitivity of 87.5%, specificity of
      100%, and overall predictive accuracy of 94%. All NO responders tolerated a full
      nifedipine trial without hypotension. There was a highly significant correlation
      between the effects of NO and nifedipine on PVR (r=0.67, p=0.003). CONCLUSIONS:
      The pulmonary vascular response to inhaled NO accurately predicts the acute
      hemodynamic response to nifedipine in PPH, and a positive response to NO is
      associated with a safe nifedipine trial. In patients comparable with those
      evaluated, a trial of nifedipine in NO nonresponders appears unwarranted and
      potentially dangerous.

PMID- 9768735
TI  - Quantification of mitral regurgitation by automated cardiac output measurement:
      experimental and clinical validation.
AB  - OBJECTIVES: To develop and validate an automated noninvasive method to quantify
      mitral regurgitation. BACKGROUND: Automated cardiac output measurement (ACM),
      which integrates digital color Doppler velocities in space and in time, has been
      validated for the left ventricular (LV) outflow tract but has not been tested for
      the LV inflow tract or to assess mitral regurgitation (MR). METHODS: First, to
      validate ACM against a gold standard (ultrasonic flow meter), 8 dogs were studied
      at 40 different stages of cardiac output (CO). Second, to compare ACM to the LV
      outflow (ACMa) and inflow (ACMm) tracts, 50 normal volunteers without MR or
      aortic regurgitation (44+/-5 years, 31 male) were studied. Third, to compare ACM
      with the standard pulsed Doppler-two-dimensional echocardiographic (PD-2D) method
      for quantification of MR, 51 patients (61+/-14 years, 30 male) with MR were
      studied. RESULTS: In the canine studies, CO by ACM (1.32+/-0.3 liter/min, y) and
      flow meter (1.35+/-0.3 liter/min, x) showed good correlation (r=0.95,
      y=0.89x+0.11) and agreement (deltaCO(y-x)=0.03+/-0.08 [mean+/-SD] liter/min). In
      the normal subjects, CO measured by ACMm agreed with CO by ACMa (r=0.90, p <
      0.0001, deltaCO=-0.09+/-0.42 liter/min), PD (r=0.87, p < 0.0001, deltaCO=0.12+/
      0.49 liter/min) and 2D (r=0.84, p < 0.0001, deltaCO=-0.16+/-0.48 liter/min). In
      the patients, mitral regurgitant volume (MRV) by ACMm-ACMa agreed with PD-2D (r=
      0.88, y=0.88x+6.6, p < 0.0001, deltaMRV=2.68+/-9.7 ml). CONCLUSIONS: We
      determined that ACM is a feasible new method for quantifying LV outflow and
      inflow volume to measure MRV and that ACM automatically performs calculations
      that are equivalent to more time-consuming Doppler and 2D measurements.
      Additionally, ACM should improve MR quantification in routine clinical practice.

PMID- 9768736
TI  - Early age at repair prevents restrictive right ventricular (RV) physiology after
      surgery for tetralogy of Fallot (TOF): diastolic RV function after TOF repair in
      infancy.
AB  - OBJECTIVES: To assess diastolic right ventricular (RV) physiology after tetralogy
      of Fallot repair in infancy. BACKGROUND: Restrictive RV physiology after
      tetralogy of Fallot repair is related to type of repair, pulmonary regurgitation,
      and late arrhythmias. METHODS: Forty-seven patients were investigated, 27 and 20
      patients in Lund and London, respectively. Median age at repair was 0.78 years
      (0.08-0.99) and median follow-up was 3.0 years (0.08-10.4). Restrictive RV
      physiology was assessed by Doppler echocardiography. RESULTS: Thirteen patients
      (28%) had restrictive RV physiology at follow-up, three of 19 patients (16%) with
      transatrial repair and 10 of 28 patients (32%) with transventricular repair,
      respectively (p=0.1). Ten percent of the patients repaired before 6 months of age
      were restrictive at follow-up, increasing to 38% with repair after 9 months.
      Transannular patch (TAP) repair was performed in 55% of the patients, including
      eight of 10 patients (80%) with repair before 6 months of age. Thirty-one percent
      of the patients with TAP repair were restrictive. These restrictive patients had
      more severe preoperative pulmonary stenosis (p < 0.05), were older at repair (p <
      0.05), and had shorter duration of pulmonary regurgitation (p < 0.001) at follow
      up. CONCLUSIONS: Restrictive RV physiology is inversely related to age at repair
      and independent of type of outflow tract repair. Since TAP repair is more common
      in early repair, and restriction seems to be less frequent, long-term follow-up
      to assess adverse effects of pulmonary regurgitation is mandatory.

PMID- 9768737
TI  - Effect of myocardial hypertrophy on systolic and diastolic function in children:
      insights from the force-frequency and relaxation-frequency relationships.
AB  - OBJECTIVE: The objective of this study was to evaluate the effect of myocardial
      hypertrophy on systolic and diastolic properties of the left ventricle in
      children. BACKGROUND: In children with myocardial hypertrophy, ejection phase
      indices are invariably increased. However, indices of force-generation, e.g., end
      systolic elastance and invasive indices of diastolic properties, have been
      studied infrequently in children with myocardial hypertrophy. METHODS: We studied
      10 children with congenital aortic stenosis or coarctation of aorta and nine
      control patients. Systolic properties were assessed from shortening fraction, end
      systolic fiber elastance (Ef(es)) measured at resting heart rates, and force
      frequency relationship measured at heart rates increasing from 110 to 160 beats
      per minute. Diastolic properties were assessed from time constant of relaxation
      (tau) at matched heart rates, chamber stiffness constant, myocardial stiffness
      constant, and relaxation-frequency relationship measured at gradually increasing
      heart rates. RESULTS: Ef(es) remained unchanged by myocardial hypertrophy,
      however, tau was prolonged (tauL: 27.3+/-2.3 vs. 21.8+/-2.2 ms, p < 0.001; and
      tauD: 43.2+/-3.1 vs. 34.3+/-3.3 ms, p < 0.001). Both chamber and myocardial
      stiffness constants remained unchanged. Incremental increases in heart rate
      produced incremental improvement in both contraction and relaxation. Slopes of
      force-frequency and relaxation-frequency relationships remained unchanged in the
      experimental group. However, the relaxation-frequency relationship manifested a
      parallel shift upward. CONCLUSIONS: In conscious, sedated children with
      myocardial hypertrophy, systolic function assessed by an index of force
      generation remains unchanged. However, relaxation is prolonged but passive
      diastolic properties remain unaffected. The combined effect of hypertrophy and
      heart rate does not alter the force-frequency and relaxation-frequency
      relationships.

PMID- 9768738
TI  - Evaluation of dynamic changes in microvascular flow during ischemia-reperfusion
      by myocardial contrast echocardiography.
AB  - BACKGROUND: Dynamic changes of myocardial blood flow have been observed after
      reperfusion of an occluded coronary artery. MCE performed by intracoronary
      contrast injection can provide an estimate of microvascular flow. We hypothesized
      that MCE performed using intravenous infusion of a new generation contrast agent
      and electrocardiogram-gated harmonic imaging would be able to assess serial
      changes of microvascular perfusion. OBJECTIVE: To study the potential of
      myocardial contrast echocardiography (MCE) to assess serial changes of
      microvascular flow during ischemia-reperfusion. METHODS: Sixteen dogs underwent
      90 or 180 min of left anterior descending coronary occlusion, followed by 180 min
      of reperfusion. Regional blood flow (RBF) was measured with fluorescent
      microspheres at baseline, during coronary occlusion, and at 5, 30, 90, and 180
      min during reperfusion. At the same time points, MCE was performed with
      intravenous infusion of AF0150 (4 mg/min). Gated end-systolic images in short
      axis were acquired in harmonic mode and digitized on-line. Background-subtracted
      videointensity measured from MCE and RBF obtained from fluorescent microspheres
      were calculated for the risk area and for a control area, and were expressed as
      the ratio of the two areas. RESULTS: After initial hyperemia, a progressive
      reduction in flow was observed during reperfusion. MCE correctly detected the
      time course of changes in flow during occlusion-reperfusion. Videointensity ratio
      significantly correlated with RBF data (r=0.79; p < 0.0001). CONCLUSIONS: The
      progressive reduction in blood flow occurring within the postischemic
      microcirculation was accurately detected by MCE. This approach has potential
      application in the evaluation and management of postischemic reperfusion in
      humans.

PMID- 9768739
TI  - In vivo effects of contrast media on coronary thrombolysis.
AB  - OBJECTIVES: The aim of the present study was to evaluate the influence of
      radiographic contrast media (CM) on alteplase-induced coronary thrombolysis.
      BACKGROUND: Contrast media inhibit fibrinolysis in vitro and interact with
      endothelial cells, platelets and the coagulation system. The in vivo effects of
      CM on thrombolysis are not known. METHODS: Occlusive coronary artery thrombosis
      was induced in 4 groups of 10 dogs by the copper coil technique. After 70 min of
      occlusion the dogs were randomized to intracoronary injection of 2 ml kg(-1) of
      either saline, a low-osmolar ionic CM (ioxaglate), a low-osmolar nonionic CM
      (iohexol) or a high-osmolar ionic CM (amidotrizoate). Thrombolysis with alteplase
      and co-therapy with aspirin and heparin was initiated after 90 min of occlusion.
      The coronary artery flow was monitored with an electromagnetic flowmeter
      throughout the experiment. RESULTS: Iohexol and amidotrizoate, but not ioxaglate,
      were associated with longer reperfusion delays (time to optimal reperfusion: 67+/
      48 min and 65+/-49 min, respectively, vs. 21+/-11 min after placebo; p < 0.05)
      and shorter periods of coronary perfusion (optimal perfusion time: 21+/-26 min
      and 21+/-28 min, respectively, vs. 58+/-40 min after placebo; p < 0.05). No
      significant differences were observed between groups with regard to activated
      partial thromboplastin times, circulating thrombin-antithrombin III complex
      concentrations and fibrinogen. CONCLUSIONS: In this animal model administration
      of iohexol and amidotrizoate before thrombolysis significantly delayed
      reperfusion. This interaction should be considered in the design of clinical
      trials of thrombolytic therapy that evaluate coronary artery patency and in
      patients receiving local infusions of fibrinolytic agents.

PMID- 9768740
TI  - Long-term endothelial dysfunction is more pronounced after stenting than after
      balloon angioplasty in porcine coronary arteries.
AB  - OBJECTIVE: To compare percutaneous transluminal coronary angioplasty (PTCA) and
      stent implantation with respect to the long-term changes they induce in the newly
      formed endothelium in porcine coronary arteries by studying both morphological
      and functional parameters of the endothelium at 2 weeks and 3 months after
      intervention. BACKGROUND: Problems affecting PTCA or stent implantation have been
      overcome to a large extent by means of better techniques and the availability of
      new drugs. Late problems, however, still exist in that restenosis affects a large
      number of patients. With an increasing number of patients being treated with
      stents, the problem of in-stent restenosis is of even greater concern, as this
      seems difficult to treat. A functional endothelial lining is thought to be
      important in controlling the growth of the underlying vascular tissue. We
      hypothesized that the enhanced neointimal hyperplasia observed after stenting is
      associated with a more pronounced and prolonged endothelial dysfunction. METHODS:
      Arteries were analyzed using a dye-exclusion test and planimetry of permeable
      areas. Thereafter, the arteries were processed for light and scanning electron
      microscopy for assessment of morphology and proliferative response. RESULTS:
      Leakage of the endothelium for molecules such as Evans blue-albumin as well as
      prolonged endothelial proliferation is observed as late as 3 months after the
      intervention, and is more pronounced after stenting. Permeability is associated
      with distinct morphologic characteristics: endothelial retraction, the expression
      of surface folds, and the adhesion of leukocytes. CONCLUSIONS: Stenting
      especially decreases long-term vascular integrity with respect to permeability
      and endothelial proliferation, and is associated with distinct morphologic
      characteristics.

PMID- 9768742
TI  - Aspirin and newer orally active antiplatelet agents in the treatment of the post
      myocardial infarction patient.
AB  - The thienopyridine derivatives, ticlopidine and clopidogrel, provide alternatives
      to aspirin for use in the prevention of recurrent ischemic events in the post
      myocardial infarction patient. These drugs act through a different mechanism than
      aspirin and, as a result, have potentially different profiles of safety and
      efficacy. The following discusses the clinical data collected supporting the use
      of these drugs for secondary prevention and the unanswered questions that remain
      regarding their use in subpopulations of individuals at risk. Based on the
      available data, it may be concluded that aspirin should remain the drug of choice
      for the prevention of recurrent ischemic events in the majority of patients who
      have suffered a recent myocardial infarction.

PMID- 9768741
TI  - Hypertrophic remodeling: gender differences in the early response to left
      ventricular pressure overload.
AB  - OBJECTIVES: To identify gender differences in left ventricular remodeling,
      hypertrophy, and function in response to pressure overload due to ascending
      aortic banding in rats. BACKGROUND: Gender may influence the adaptation to
      pressure overload, as women with aortic stenosis have greater degrees of left
      ventricular hypertrophy and better left ventricular function than men. METHODS:
      Fifty-two weanling rats underwent ascending aortic banding (16 males, 18
      females), or sham surgery (9 males, 9 females). At 6 and 20 weeks, rats underwent
      transthoracic echo Doppler studies, and closed-chest left ventricular pressures
      with direct left ventricular puncture. Perfusion-fixed tissues from eight rats
      were examined morphometrically for myocyte cross-sectional area and percent
      collagen volume. RESULTS: At 6 weeks after aortic banding, left ventricular
      remodeling, extent of hypertrophy, and function appeared similar in male and
      female rats. At 20 weeks, male but not female rats showed an early transition to
      heart failure, with onset of cavity dilatation (left ventricular diameter=155%
      vs. 121% of same-sex sham), loss of concentric remodeling (relative wall
      thickness=102% vs. 139% of sham), elevated wall stress (systolic stress=266% vs.
      154% of sham), and diastolic dysfunction (deceleration of rapid filling=251% vs.
      190% of sham). Left ventricular systolic pressures were higher in female compared
      with male rats (186+/-20 vs. 139+/-13 mm Hg), while diastolic pressures tended to
      be lower (14+/-4 vs. 17+/-4 mm Hg). CONCLUSIONS: Gender significantly influences
      the evolution of the early response to pressure overload, including the
      transition to heart failure in rats with aortic stenosis.

PMID- 9768743
TI  - President's Page: Practice expense: the struggle continues.

PMID- 9768744
TI  - Concerning the Fontan patient's excessive minute ventilation during exercise.

PMID- 9768745
TI  - Lipoprotein (a): an important risk factor in coronary artery disease.

PMID- 9768746
TI  - Functional assessment of coronary stenoses.

PMID- 9768747
TI  - Familial dilated cardiomyopathy.

PMID- 9768748
TI  - Cytotoxic lymphocyte recognition of HLA-E: utilizing a nonclassical window to
      peer into classical MHC.

PMID- 9768749
TI  - The transcription factor NFAT4 is involved in the generation and survival of T
      cells.
AB  - Nuclear factor of activated T cells (NFAT) is a family of four related
      transcription factors implicated in cytokine and early response gene expression
      in activated lymphocytes. Here we report that NFAT4, in contrast to NFATp and
      NFATc, is preferentially expressed in DP thymocytes. Mice lacking NFAT4 have
      impaired development of CD4 and CD8 SP thymocytes and peripheral T cells as well
      as hyperactivation of peripheral T cells. The thymic defect is characterized by
      increased apoptosis of DP thymocytes. The increased apoptosis and hyperactivation
      may reflect heightened sensitivity to TcR-mediated signaling. Further, mice
      lacking NFAT4 have impaired production of Bcl-2 mRNA and protein. NFAT4 thus
      plays an important role in the successful generation and survival of T cells.

PMID- 9768750
TI  - Differential TCR signaling regulates apoptosis and immunopathology during antigen
      responses in vivo.
AB  - Clonal selection theories postulate that lymphocyte fate is regulated by antigen
      receptor specificity. However, lymphocyte apoptosis is induced through nonantigen
      specific receptors such as Fas (CD95/APO-1) or TNFR. We define a selective TCR
      that controls apoptosis by Fas or TNFR stimulation. Variant ligands can deliver
      this "competence to die" signal without the full TCR signals necessary for
      cytokine synthesis. These partial agonists regulate T cell deletion in vivo even
      when Fas or TNF is provided by T cells of unrelated specificity, but they do not
      cause the liver necrosis that is associated with T cell elimination by the full
      agonist. Thus, selective signaling ligands regulate T cell deletion and immune
      damage in vivo and may be important for peripheral T cell tolerance.

PMID- 9768751
TI  - IL-12 acts directly on DC to promote nuclear localization of NF-kappaB and primes
      DC for IL-12 production.
AB  - We analyzed the expression of an IL-12 receptor by fresh dendritic cells (DC) and
      a DC line. Using RT-PCR, RNAse protection, and electrophoretic mobility shift
      assay analysis, we found that DC possess an IL-12 receptor with beta1 subunit
      (downstream box 1)-related differences from that on T cells. IL-12 signaling
      through this receptor involved members of the NF-KB but not STAT family. The
      unique properties of the IL-12 receptor on DC, characterized by a single class of
      binding sites with a Kd of about 325 pM, may underlie rather unique effects, such
      as IFNgamma-independent augmentation of class II antigen expression and priming
      for LPS-induced production of IL-12.

PMID- 9768752
TI  - A novel lysosome-associated membrane glycoprotein, DC-LAMP, induced upon DC
      maturation, is transiently expressed in MHC class II compartment.
AB  - We have identified a novel lysosome-associated membrane glycoprotein localized on
      chromosome 3q26.3-q27, DC-LAMP, which is homologous to CD68. DC-LAMP mRNA is
      present only in lymphoid organs and DC. A specific MAb detects the protein
      exclusively in interdigitating dendritic cells. Expression of DC-LAMP increases
      progressively during in vitro DC differentiation, but sharply upon activation
      with LPS, TNFalpha, or CD40L. Confocal microscopy confirmed the lysosomal
      distribution of the protein. Furthermore, DC-LAMP was found in the MHC class II
      compartment immediately before the translocation of MHC class II molecules to the
      cell surface, after which it concentrates into perinuclear lysosomes. This
      suggests that DC-LAMP might change the lysosome function after the transfer of
      peptide-MHC class II molecules to the surface of DC.

PMID- 9768753
TI  - Kinetics of interaction of HLA-C ligands with natural killer cell inhibitory
      receptors.
AB  - The recognition of HLA-C molecules by specific inhibitory receptors is a crucial
      step in the regulation of natural killer (NK) cell function. Using soluble,
      recombinant HLA-C molecules and NK inhibitory receptors (NKIR, members of the
      immunoglobulin superfamily), we show that HLA-C binds to NKIR molecules with
      extremely fast association and dissociation rates, among the fastest of the
      immune system interactions so far studied. These kinetics may be essential for
      the biological function of NK cells, i.e., to facilitate the rapid
      immunosurveillance of cells for absent or diminished expression of class I MHC
      proteins.

PMID- 9768754
TI  - Rapid death and regeneration of NKT cells in anti-CD3epsilon- or IL-12-treated
      mice: a major role for bone marrow in NKT cell homeostasis.
AB  - Natural killer T (NKT) cells express a T cell receptor (TCR) and markers common
      to NK cells, including NK1.1. In vivo, NKT cells are triggered by anti-CD3epsilon
      MAb to rapidly produce large amounts of IL-4 and by IL-12 to reject tumors. We
      show here that anti-CD3epsilon MAb treatment rapidly depletes the liver (and
      partially the spleen) of NKT cells and that homeostasis is achieved 1 to 2 days
      later via NKT cell proliferation that occurs mainly in bone marrow. Similar
      results were obtained in mice treated with IL-12. Collectively, our data
      demonstrate that peripheral NKT cells are highly sensitive to activation-induced
      cell death and that bone marrow plays a major role in restoring NKT cell
      homeostasis.

PMID- 9768755
TI  - Targeted disruption of the catalytic subunit of the DNA-PK gene in mice confers
      severe combined immunodeficiency and radiosensitivity.
AB  - The DNA-dependent protein kinase is a mammalian protein complex composed of Ku70,
      Ku80, and DNA-PKcs subunits that has been implicated in DNA double-strand break
      repair and V(D)J recombination. Here, by gene targeting, we have constructed a
      mouse with a disruption in the kinase domain of DNA-PKcs, generating an animal
      model completely devoid of DNA-PK activity. Our results demonstrate that DNA-PK
      activity is required for coding but not for signal join formation in mice.
      Although our DNA-PKcs defective mice closely resemble Scid mice, they differ by
      having elevated numbers of CD4+CD8+ thymocytes. This suggests that the Scid mice
      may not represent a null phenotype and may retain some residual DNA-PKcs
      function.

PMID- 9768756
TI  - A targeted DNA-PKcs-null mutation reveals DNA-PK-independent functions for KU in
      V(D)J recombination.
AB  - The DNA-dependent protein kinase (DNA-PK) consists of Ku70, Ku80, and a large
      catalytic subunit, DNA-PKcs. Targeted inactivation of the Ku70 or Ku80 genes
      results in elevated ionizing radiation (IR) sensitivity and inability to perform
      both V(D)J coding-end and signal (RS)-end joining in cells, with severe growth
      retardation plus immunodeficiency in mice. In contrast, we now demonstrate that
      DNA-PKcs-null mice generated by gene-targeted mutation, while also severely
      immunodeficient, exhibit no growth retardation. Furthermore, DNA-PKcs-null cells
      are blocked for V(D)J coding-end joining, but retain normal RS-end joining.
      Finally, while DNA-PK-null fibroblasts exhibited increased IR sensitivity, DNA
      PKcs-deficient ES cells did not. We conclude that Ku70 and Ku80 may have
      functions in V(D)J recombination and DNA repair that are independent of DNA-PKcs.

PMID- 9768757
TI  - The structure of HLA-DM, the peptide exchange catalyst that loads antigen onto
      class II MHC molecules during antigen presentation.
AB  - The three-dimensional structure of the soluble ecto-domain of HLA-DM has been
      determined to 2.5 A resolution by X-ray crystallography. HLA-DM has both peptide
      exchange activity and acts as a chaperone to peptide-free class II MHC molecules.
      As predicted, the structure is similar to that of classical class II MHC
      molecules except that the peptide-binding site is altered to an almost fully
      closed groove. An unusual cavity is found at the center of the region that binds
      peptides in class II MHC molecules, and a tryptophanrich lateral surface is
      identified that is a candidate both for binding to HLA-DR, to effect catalysis,
      and to HLA-DO, an inhibitor.

PMID- 9768758
TI  - Crystal structure of mouse H2-M.
AB  - H2-M (HLA-DM in humans) resides in an acidic endosomal compartment, where it
      facilitates the loading of antigenic peptides into the peptide-binding groove of
      class II MHC. The crystal structure of a soluble form of H2-M has been solved to
      3.1 A resolution, revealing a heterodimer with structural similarities to the MHC
      family of proteins. In contrast to its antigen-presenting cousins, the membrane
      distal alpha helices of H2-M pack closely together, occluding most of the binding
      groove except for a single large pocket near the center. The structure of H2-M
      has several unique features that may play a role in its function as a molecular
      chaperone and peptide exchange factor.

PMID- 9768759
TI  - EBV persistence in memory B cells in vivo.
AB  - Epstein-Barr virus establishes latency in vitro by activating human B cells to
      become proliferating blasts, but in vivo it is benign. In the peripheral blood,
      the virus resides latently in resting B cells that we now show are restricted to
      the sIgD memory subset. However, in tonsils the virus shows no such restriction.
      We propose that EBV indiscriminately infects B cells in mucosal lymphoid tissue
      and that these cells differentiate to become resting memory B cells that then
      enter the circulation. Activation to the blastoid stage of latency is an
      essential intermediate step in this process. Thus, EBV may persist by exploiting
      the mechanisms that produce and maintain long-term B cell memory.

PMID- 9768760
TI  - Epstein-Barr virus LMP2A drives B cell development and survival in the absence of
      normal B cell receptor signals.
AB  - Epstein-Barr virus (EBV) establishes a persistent latent infection in peripheral
      B lymphocytes in humans and is associated with a variety of malignancies and
      proliferative disorders. Latent membrane protein 2A (LMP2A) is one of only two
      viral proteins expressed in latently infected B lymphocytes in vivo. LMP2A blocks
      B cell receptor (BCR) signal transduction in vitro by binding the Syk and Lyn
      protein tyrosine kinases. To analyze the significance of LMP2A expression in
      vivo, transgenic mice with B cell lineage expression of LMP2A were generated.
      LMP2A expression results in the bypass of normal B lymphocyte developmental
      checkpoints allowing immunoglobulin-negative cells to colonize peripheral
      lymphoid organs, indicating that LMP2A possesses a constitutive signaling
      activity in nontransformed cells.

PMID- 9768761
TI  - The pathway for processing leader-derived peptides that regulate the maturation
      and expression of Qa-1b.
AB  - Qa-1b and its human homolog, HLA-E, predominantly bind leader peptides derived
      from other class I molecules. Their presentation is TAP-dependent and proteasome
      independent. We demonstrate that Dd targeted to the cytosol does not generate the
      Qa-1b peptide epitope even in the presence of lactacystin. Cells expressing
      herpes virus ICP-47 block the generation of this epitope, demonstrating that TAP
      functions in the transport of the peptide from cytosol to ER. This reveals a
      pathway for antigen presentation of leader peptides that involves translocation
      of a protein to the ER where its leader is cleaved followed by its release into
      the cytosol and transport back into the ER. Further, it ensures that Qa-1b
      expression mirrors the normal expression of class Ia molecules.

PMID- 9768762
TI  - Impaired development of Th2 cells in IL-13-deficient mice.
AB  - We report that Th2 cell cultures generated using T cells or splenocytes from IL
      13-deficient mice produce significantly reduced levels of IL-4, IL-5, and IL-10
      compared with wild-type. In contrast, IL-4 and IL-5 production by mast cells
      stimulated in vitro with PMA, ionomycin, or IgE cross-linking are unaffected. In
      vitro Th2 cell differentiation cannot be rescued by the addition of exogenous
      factors, but in vivo antigen challenge and administration of IL-13 can increase
      Th2-like cytokine responses as can infection with the parasitic nematode
      Nippostrongylus brasiliensis. IL-13-deficient mice also have lower basal levels
      of serum IgE and biased antigen-specific immunoglobulin responses. Thus, IL-13 is
      an important regulator of Th2 commitment and may therefore play a central role in
      atopy and infectious diseases.

PMID- 9768763
TI  - Should induced hypertension be beneficial after traumatic brain injury?

PMID- 9768764
TI  - Gastric fluid volume: is it really a risk factor for pulmonary aspiration?

PMID- 9768765
TI  - Gastric contents in children presenting for upper endoscopy.
AB  - Previous studies of gastric contents in children presenting for surgery
      specifically excluded those with gastrointestinal disorders. Because these
      children often need sedation or anesthesia for procedures such as upper
      endoscopy, it is important to determine the gastric fluid volume and pH in this
      group to better characterize their risk of aspiration. We therefore analyzed the
      gastric fluid volume and pH of children with a variety of gastrointestinal
      symptoms presenting for upper endoscopy. After obtaining institutional review
      board approval, the stomach contents of 248 children (aged 2 mo to 18 yr)
      presenting for upper endoscopy were prospectively measured under direct
      endoscopic vision. Children were fasted for both solids and liquids for at least
      6 h (<6 mo) or 8 h (>6 mo). Gastric fluid pH was measured using pH paper.
      Children received either deep sedation or general anesthesia and were grouped
      according to their presenting diagnosis. Results were analyzed by using analysis
      of variance, Kruskal-Wallis, and correlation (P value < 0.05). The mean gastric
      fluid volume was 0.35 +/- 0.45 mL/kg (range 0-3.14 mL/kg), and the mean gastric
      fluid pH was 1.37 +/- 1.6 (range 1-7). Of the children, 33% had gastric fluid
      volumes >0.4 mL/kg, 87% had gastric fluid pH <2.5, and 30% had gastric fluid
      volume >0.4 mL/kg and pH <2.5. Children with the presenting complaint of
      abdominal pain had the largest gastric fluid volumes. These data are not
      appreciably different from historical controls (healthy children fasted for an
      equivalent period of time who did not have gastrointestinal symptoms).
      IMPLICATIONS: When fasted for at least 6-8 h, children with a history of
      gastrointestinal symptoms presenting for upper endoscopy did not have gastric
      contents with increased volume and acidity compared with previously published
      groups of children without gastric symptoms who were fasted the same length of
      time. These results do not support the argument that children with
      gastrointestinal symptoms pose an increased anesthetic risk for aspiration.

PMID- 9768766
TI  - A granisetron-droperidol combination prevents postoperative vomiting in children.
AB  - This study was performed to compare the efficacy of a granisetron-droperidol
      combination with each antiemetic alone to prevent postoperative vomiting after
      tonsillectomy with or without adenoidectomy in children. One hundred eighty
      pediatric patients, ASA physical status I, aged 4-10 yr, were enrolled in a
      prospective, randomized, double-blind investigation and assigned to one of three
      treatment regimens: granisetron 40 microg/kg (Group G), droperidol 50 microg/kg
      (Group D), or granisetron 40 microg/kg plus droperidol 50 microg/kg (Group GD) (n
      = 60 in each group). These drugs were administered i.v. after an inhaled
      induction. The same standard general anesthetic technique and postoperative
      analgesia were used throughout. The rate of complete response, defined as no
      emesis and no need for rescue antiemetic, 0-3 h after anesthesia was 83% in Group
      G, 60% in Group D, and 97% in Group GD (P = 0.029 versus Group G, P = 0.001
      versus Group D). The corresponding rates 3-24 h after anesthesia were 83%, 55%,
      and 97% (P = 0.029 versus Group G, P = 0.001 versus Group D). No clinically
      important adverse events were observed in any of the groups. In conclusion, a
      granisetron-droperidol combination is superior to each antiemetic alone in
      complete response in children undergoing general anesthesia for tonsillectomy.
      IMPLICATIONS: We compared the efficacy of granisetron plus droperidol with each
      antiemetic alone for the prevention of postoperative vomiting in children. The
      granisetron-droperidol combination was highly effective against postoperative
      emesis.

PMID- 9768767
TI  - A comparison of three modes of ventilation with the use of an adult circle system
      in an infant lung model.
AB  - We examined the efficiency of an adult circle system with adult bellows to
      deliver minute ventilation (VE) to an infant test lung model. A Narkomed 2B
      system (North American Drager, Telford, PA) using three modes of ventilator setup
      were used: A = time-cycled, volume-controlled using bellows excursion to control
      delivered volume; B = time-cycled, pressure-controlled using inspiratory pressure
      limit adjustment to control delivered volume; C = time-cycled, pressure
      controlled using the inspiratory flow adjustment to control delivered volume. VE
      was measured with two compliances (normal and low) and four endotracheal tube
      (ETT) sizes (2.5-, 3.0-, 3.5-, and 4.0-mm inner diameter). VE was measured at
      peak inspiratory pressures (PIP) of 20, 30, 40 or 50 cm H2O while respiratory
      rate (RR) was held constant at 20 breaths/min. VE was measured as RR was set at
      20, 30, 40, or 50 breaths/min while target PIP was held constant at 20 cm H2O.
      Data were analyzed using the multiple regression technique. With the low
      compliance model, VE was nearly identical regardless of the ventilator setup.
      With the normal compliance model, minor differences in VE were observed,
      especially at the highest RR and PIP. VE was dependent on RR, PIP, and lung
      compliance. Overall, the ventilator setup resulted in minor changes in VE. Very
      high PIPs were required to deliver VE to the low compliance model. ETT size did
      not affect VE when lung compliance was low; however, smaller ETT size was a
      factor when test lung compliance was normal, decreasing delivered VE at higher
      PIP and RR. We conclude that with a Narkomed 2B adult circle system VE is
      dependent on PIP, RR, and lung compliance, but not on mode of ventilator setup.
      IMPLICATIONS: The results of this laboratory investigation indicate that when an
      adult circle system is used during infant anesthesia, the ventilation delivered
      depends primarily on the respiratory rate, peak inspiratory pressure, and the
      compliance of the lung being ventilated, rather than on the specific mode of
      ventilator setup.

PMID- 9768768
TI  - Decreased mivacurium requirements and delayed neuromuscular recovery during
      sevoflurane anesthesia in children and adults.
AB  - The purpose of this study was to compare the mivacurium infusion requirements and
      neuromuscular recovery in adults and children during propofol/opioid and
      sevoflurane anesthesia. Seventy-five adult and 75 pediatric patients were
      randomized to receive propofol/opioid 0.5 or 1.0 minimum alveolar anesthetic
      concentration (MAC) (age-related) sevoflurane anesthesia. Plasma cholinesterase
      (PChE) activity was measured. Neuromuscular blockade was monitored by train-of
      four (TOF) stimulation every 10 s and adductor pollicis electromyography. A bolus
      of 2 x the 95% effective dose of mivacurium (0.25 mg/kg) was followed by an
      infusion titrated to maintain 90%-95% blockade. Mivacurium doses were recorded
      every 5 min. At the end of surgery, the infusion was stopped, and recovery from
      mivacurium was monitored until TOF > or =0.7. PChE concentrations were within the
      normal range (adults 4-12 KU/L, children 6-16 KU/L) and correlated with
      mivacurium dose. Mivacurium infusion rates were higher in children than in
      adults: at 30 min, the rates in children were 13.1 +/- 6.4, 8.1 +/- 4.7, and 5.2
      +/- 2.9 microg x kg(-1) x min(-1) at 0, 0.5, and 1.0 MAC sevoflurane,
      respectively; the corresponding rates in adults were 5.9 +/- 3.1, 4.3 +/- 1.7,
      and 2.9 +/- 0.7 microg x kg(-1) x min(-1) (P < 0.01). Sevoflurane decreased
      mivacurium requirements, maximal decreases at 45 min in children and 10 min in
      adults, and delayed neuromuscular function recovery. Children recovered twice as
      quickly as adults, achieving TOF > or =0.7 at 9.8 +/- 2.5, 11.4 +/- 2.8, and 19.6
      +/- 6.3 min compared with 19.9 +/- 5.4, 26.4 +/- 8.3, and 32.9 +/- 9.8 min in
      adults (P < 0.0001). In conclusion, mivacurium requirements were correlated with
      PChE, were greater in children than in adults, and were reduced by sevoflurane.
      Neuromuscular recovery occurred more rapidly in children and was delayed by
      sevoflurane. IMPLICATIONS: The mivacurium infusion requirement to maintain
      constant 90%-95% neuromuscular block during anesthesia is correlated with plasma
      cholinesterase activity. It is increased in children and reduced by the inhaled
      anesthetic sevoflurane. Despite the larger dose administered to children,
      recovery from block occurred more rapidly in children than in adults and was
      delayed by sevoflurane.

PMID- 9768769
TI  - Anaphylactoid reaction due to the administration of ondansetron in a pediatric
      neurosurgical patient.

PMID- 9768770
TI  - Protamine reversal of heparin affects platelet aggregation and activated clotting
      time after cardiopulmonary bypass.
AB  - Bleeding after cardiopulmonary bypass (CPB) is related to multiple factors.
      Excess protamine weakens clot structure and decreases platelet function;
      therefore, an increased activated clotting time (ACT) after protamine reversal of
      heparin may be misinterpreted as residual heparin anticoagulation. We evaluated
      the effects of protamine, recombinant platelet factor 4 (rPF4), and
      hexadimethrine on ACT in blood obtained after CPB. In addition, we examined the
      effect of protamine on in vitro platelet aggregation. Incremental doses of
      protamine, rPF4, and hexadimethrine were added to heparinized blood from CPB, and
      ACTs were performed. Incremental concentrations of protamine were added to
      heparinized platelet-rich plasma, and aggregometry was induced by adenosine
      diphosphate (ADP) and collagen. The mean heparin concentration at the end of CPB
      was 3.3 U/mL. Protamine to heparin ratios >1.3:1 produced a significant
      prolongation of the ACT that was not seen with rPF4 and was observed only with
      5:1 hexadimethrine to heparin ratios. ADP-induced platelet aggregation was
      reduced with protamine administration > or =1.3:1. Excessive protamine reversal
      of heparin prolongs ACT and alters ADP-induced platelet aggregation in a dose
      dependent manner in vitro. Additional protamine administered to treat a prolonged
      ACT may further increase clotting time, reduce platelet aggregation, and
      potentially contribute to excess bleeding after CPB. IMPLICATIONS: We found that
      excess protamine prolonged the activated clotting time and altered platelet
      function after cardiopulmonary bypass, whereas heparin antagonists, such as
      recombinant platelet factor 4 and hexadimethrine, exhibited a wider therapeutic
      range without adversely affecting the activated clotting time. Approaches to
      avoid excess protamine or use of alternative heparin antagonists after
      cardiopulmonary bypass may be beneficial.

PMID- 9768771
TI  - Uncompensated blood loss is not tolerated during acute normovolemic hemodilution
      in anesthetized pigs.
AB  - Clinically, hemodilution to a hematocrit of 9% has been studied, but the effects
      of hypovolemia during this degree of hemodilution have not been elucidated. We
      studied the response to blood loss during extreme hemodilution and evaluated
      indicators of hypovolemia. Systemic and myocardial hemodynamics, oxygen
      transport, and blood lactate concentrations were measured in 12 anesthetized pigs
      exposed to a graded blood loss of 10, 20, 30, and 40 mL/kg. Six animals were
      hemodiluted (hematocrit 10.8% +/- 1.4%, mean +/- SD), and six animals served as
      controls (hematocrit 34.6% +/- 1.5%). Hemodilution decreased systemic oxygen
      delivery to 9.5 +/- 0.6 mL x kg(-1) x min(-1) (controls 21.7 +/- 3.9 mL x kg(-1)
      x min(-1)) (P < 0.01) despite a 31% increase in cardiac output. Systemic oxygen
      uptake was unchanged. Arterial lactate increased to 3.3 +/- 1.1 mM/L (controls
      1.6 +/- 0.6 mM/L) (P < 0.05), and mixed venous oxygen saturation (SvO2) decreased
      to 38.2% + 4.8% (controls 68.6% +/- 2.9%) (P < 0.01). At a blood loss of 10
      mL/kg, cardiac output continued to be greater in the hemodiluted animals (P <
      0.01). Arterial blood pressure decreased to 61 +/- 8 mmHg (controls 84 +/- 18 mm
      Hg) (P < 0.05), whereas heart rate was unchanged. Systemic oxygen delivery
      decreased to 8.8 +/- 1.2 mL x kg(-1) x min(-1) (controls 14.1 +/- 2.5 mL x kg(-1)
      x min(-1)) (P < 0.01). Systemic oxygen uptake was maintained by a further
      increase in oxygen extraction, and SvO2 decreased to 29.7% +/- 7.3%, compared
      with 55.3% +/- 9.0% in controls (P < 0.01). Arterial lactate increased to 4.9 +/-
      1.4 mM/L (controls 1.8 +/- 0.8 mM/L) (P < 0.01). Myocardial oxygen delivery and
      lactate uptake were unchanged. When the blood loss equaled 30 mL/kg, myocardial
      lactate production occurred, and two hemodiluted animals died of circulatory
      failure. Central venous and capillary wedge pressures changed minimally during
      the blood loss and did not differ between groups. We conclude that a decrease in
      arterial blood pressure and SvO2 were early signs of hypovolemia during
      hemodilution, whereas central venous pressure and pulmonary capillary wedge
      pressure were insensitive indicators. IMPLICATIONS: Anesthetized pigs with
      extremely low hemoglobin levels (one third of normal) showed poor tolerance to
      blood loss >10 mL/kg. A decreasing arterial blood pressure, a decreasing oxygen
      saturation in the venous blood, and an increase in arterial blood lactate
      concentration were useful indicators of blood loss.

PMID- 9768772
TI  - Dexamethasone decreases the incidence of shivering after cardiac surgery: a
      randomized, double-blind, placebo-controlled study.
AB  - Shivering after cardiac surgery is common, and may be a result of intraoperative
      hypothermia. Another possible etiology is fever and chills secondary to
      activation of the inflammatory response and release of cytokines by
      cardiopulmonary bypass. Dexamethasone decreases the gradient between core and
      skin temperature and modifies the inflammatory response. The goal of this study
      was to determine whether dexamethasone can reduce the incidence of shivering. Two
      hundred thirty-six patients scheduled for elective coronary and/or valvular
      surgery were randomly assigned to receive either dexamethasone 0.6 mg/kg or
      placebo after the induction of anesthesia. All patients received standard
      monitoring and anesthetic management. After arrival in the intensive care unit
      (ICU), nurses unaware of the treatment groups recorded visible shivering, as well
      as skin and pulmonary artery temperatures. Analysis of shivering rates was
      performed by using chi2 tests and logistic regression analysis. Compared with
      placebo, dexamethasone decreased the incidence of shivering (33.0% vs 13.1%; P =
      0.001). It was an independent predictor of reduced incidence of shivering and was
      also associated with a higher skin temperature on ICU admission and a lower
      central temperature in the early postoperative period. IMPLICATIONS:
      Dexamethasone is effective in decreasing the incidence of shivering. The
      effectiveness of dexamethasone is independent of temperature and duration of
      cardiopulmonary bypass. Shivering after cardiac surgery may be part of the
      febrile response that occurs after release of cytokines during cardiopulmonary
      bypass.

PMID- 9768773
TI  - Desflurane and isoflurane produce similar alterations in systemic and pulmonary
      hemodynamics and arterial oxygenation in patients undergoing one-lung ventilation
      during thoracotomy.
AB  - We tested the hypothesis that desflurane (DES) and isoflurane (ISO) produce
      similar effects on systemic and pulmonary hemodynamics and arterial oxygenation
      before, during, and after one-lung ventilation (OLV) in patients undergoing
      thoracotomy. After obtaining informed consent, anesthesia was induced with sodium
      thiopental or thiamylal, fentanyl, and vecuronium in 61 ASA physical status II-IV
      patients. Patients were randomly assigned to receive either DES (n = 30) or ISO
      (n = 31) in 100% O2 in separate groups. Hemodynamic data (radial and pulmonary
      artery [PA] catheters) were recorded, and blood gas values were obtained before
      and after induction; at selected intervals before, during, and after OLV; and
      before emergence. DES significantly (P < 0.05) increased heart rate (HR) and
      decreased mean arterial pressure (MAP) and cardiac output (CO). PA pressures and
      pulmonary vascular resistance (PVR) increased; systemic vascular resistance (SVR)
      was unchanged. Increases in HR and CO and decreases in MAP and SVR occurred
      during OLV and DES. Reductions in PaO2 (411 +/- 88 to 271 +/- 131 mm Hg 5 min
      after beginning OLV; mean +/- SD) and content (CaO2) and increases in shunt
      fraction (Qs/Qt; 0.25 +/- 0.12 to 0.40 +/- 0.19 at 5 min after beginning OLV)
      were also observed. ISO increased HR and PA pressures but did not alter MAP, CO,
      and PVR, in contrast to the findings with DES. Reductions in MAP and SVR and
      increases in CO and PA pressures were observed during OLV in the presence of ISO.
      Similar to the findings during DES, decreases in PaO2 and CaO2 and increases in
      Qs/Qt occurred during OLV and ISO. We conclude that DES and ISO produce very
      similar alterations in systemic and pulmonary hemodynamics and arterial
      oxygenation in patients undergoing OLV during thoracotomy. IMPLICATIONS:
      Desflurane and isoflurane produce similar cardiovascular and pulmonary effects
      before, during, and after one-lung ventilation in patients undergoing lung
      surgery.

PMID- 9768774
TI  - The effect of magnesium sulphate on hemodynamics and its efficacy in attenuating
      the response to endotracheal intubation in patients with coronary artery disease.
AB  - Laryngoscopy and endotracheal intubation may produce adverse hemodynamic effects.
      Magnesium has direct vasodilating properties on coronary arteries and inhibits
      catecholamine release, thus attenuating the hemodynamic effects during
      endotracheal intubation. We studied 36 patients with coronary artery disease
      (CAD) scheduled for elective coronary artery bypass grafting to evaluate the
      hemodynamic effects of magnesium and its efficacy in attenuating the response to
      endotracheal intubation. Patients received either 0.1 mL/kg (50%) magnesium
      sulfate (50 mg/kg) (Group A, n = 19) or isotonic sodium chloride solution (Group
      B, n = 17) before the induction of anesthesia and 0.05 mL/kg of isotonic sodium
      chloride solution (Group A) or lidocaine 2% (1 mg/kg) (Group B) before
      intubation. The hemodynamic variables were recorded before induction, after the
      trial drug, after induction, and after endotracheal intubation. Automatic ST
      segment analysis was performed throughout the study period. Magnesium sulfate
      administration was associated with increased cardiac index (P < 0.01), a minimal
      increase in heart rate, and a significant decrease in mean arterial pressure
      (MAP) and systemic vascular resistance (SVR) (P < 0.001). None of the patients in
      the magnesium group had significant ST depression compared with three patients in
      the control group. The magnesium group patients had a significantly lesser
      increase in MAP (P < 0.05) and SVR (P < 0.01) compared with the control group
      patients who received lidocaine before endotracheal intubation. Thus, magnesium
      is an useful adjuvant to attenuate endotracheal intubation response in patients
      with CAD. IMPLICATIONS: Endotracheal intubation produces adverse hemodynamic
      effects, which may be more detrimental in patients with coronary artery disease
      than in healthy patients. The present study shows that magnesium administered
      before endotracheal intubation can attenuate this response better than lidocaine.

PMID- 9768775
TI  - Pulmonary hypertension and major surgery.

PMID- 9768776
TI  - Factors affecting discharge time in adult outpatients.
AB  - Discharge time (total recovery time) is one determinant of the overall cost of
      outpatient surgery. We performed this study to determine what factors affect
      discharge time. Details regarding patients, anesthesia, surgery, and recovery
      were recorded prospectively for 1088 adult patients undergoing ambulatory surgery
      over an 8-mo period. The contribution of factors to variability in the discharge
      time was assessed by using multivariate linear regression analysis. In the last 4
      mo of the study, nurses indicated the causes of discharge delays > or =50 min in
      Phase 1 or > or =70 min in Phase 2 recovery. When all anesthetic techniques were
      included, anesthetic technique was the most important determinant of discharge
      time (R2 = 0.10-0.15; P = 0.001), followed by the Phase 2 nurse. After general
      anesthesia, the Phase 2 nurse was the most important factor (R2 = 0.13; P = 0.01
      0.001). In women, the choice of general anesthetic drugs was significant (R2 =
      0.04; P = 0.002). The three most common medical causes of delay were pain,
      drowsiness, and nausea/vomiting. System factors were the foremost cause of Phase
      2 delays (41%), with lack of immediate availability of an escort accounting for
      53% of system-related delays. We conclude that efforts to shorten discharge time
      would best be directed at improving nursing efficiency; ensuring availability of
      an escort for the patient; and preventing postoperative pain, drowsiness, and
      emetic symptoms. The selection of anesthetic technique and anesthetic drug seems
      to be of selective importance in determining discharge time depending on patient
      gender and type of surgery. IMPLICATIONS: The relative importance of anesthetic
      and nonanesthetic factors were evaluated as determinants of discharge time after
      ambulatory surgery. Postoperative nursing care was the single most important
      factor after general anesthesia; anesthetic drugs, anesthetic technique, and
      prevention of pain and emetic symptoms were of selective importance depending on
      patient gender and type of surgery.

PMID- 9768777
TI  - A total intravenous anesthetic technique for outpatient facial laser resurfacing.

PMID- 9768778
TI  - A survey on the intended purposes and perceived utility of preoperative
      cardiology consultations.
AB  - Cardiology consultations are often requested by surgeons and anesthesiologists
      for patients with cardiovascular disease. There can be confusion, however,
      regarding both the reasons for a consultation and their effect on patient
      management. This study was designed to determine the attitudes of physicians
      toward preoperative cardiology consultations and to assess the effect of such
      consultations on perioperative management. A multiple-choice survey regarding the
      purposes and utility of cardiology consultations was sent to randomly selected
      New York metropolitan area anesthesiologists, surgeons, and cardiologists. In
      addition, the charts of 55 consecutive patients aged >50 yr who received
      preoperative cardiology consultations were examined to determine the stated
      purpose of the consult, recommendations made, and concordance by surgeons and
      anesthesiologists with cardiologists' recommendations. Of the 400 surveys sent to
      each specialty, 192 were returned from anesthesiologists, 113 were returned from
      surgeons, and 129 were returned from cardiologists. There was substantial
      disagreement on the importance and purposes of a cardiology consult:
      intraoperative monitoring, "clearing the patient for surgery," and advising as to
      the safest type of anesthesia were regarded as important by most cardiologists
      and surgeons but as unimportant by anesthesiologists (all P < 0.05). Most
      surgeons (80.2%) felt obligated to follow a cardiologist's recommendations,
      whereas few anesthesiologists (16.6%) felt so obligated (P < 0.05). The most
      commonly stated purpose of the 55 cardiology consultations examined was
      "preoperative evaluation." Only 5 of these (9%) were obtained for patients in
      whom there was a new finding. Of the cardiology consultations, 40% contained no
      recommendations other than "proceed with case," "cleared for surgery," or
      "continue current medications." Recommendations regarding intraoperative
      monitoring or cardiac medications were largely ignored. IMPLICATIONS: We conclude
      that there seems to be considerable disagreement among anesthesiologists,
      cardiologists, and surgeons as to the purposes and utility of cardiology
      consultations. A review of 55 consecutive cardiology consultations suggests that
      most of them give little advice that truly affects management.

PMID- 9768779
TI  - Long-term pharmaceutical cost reduction using a data management system.
AB  - Cost containment is an important issue in medicine today, and the ability to
      control costs and maintain quality patient care presents a challenge to
      practitioners. Educating practitioners about drug costs has been identified as an
      effective method, but the benefits of education are usually short-lived. To
      evaluate the role of education in cost control, pharmaceutical use and
      performance improvement data were analyzed at a tertiary care institution during
      two time periods. A total of 4,530 anesthesia records and associated performance
      improvement data from March to June 1993 were analyzed as a baseline. These data
      were shared with the clinicians of an anesthesia department and used to educate
      practitioners regarding the costs and use of injectable pharmaceuticals and to
      identify areas in which cost savings could be achieved. The same information from
      10,600 cases during January to October 1996 were compared with the early group.
      The expenditures for injectable pharmaceuticals to provide anesthesia were
      decreased by more than $30,000 per month, or $32 per case, without changing the
      performance indicators that were monitored, and has been maintained for >3 yr.
      IMPLICATIONS: By using a data management system, the cost for medications to
      provide anesthesia has been reduced without changing the quality of patient care.

PMID- 9768780
TI  - Reliability of the transient hyperemic response test in detecting changes in
      cerebral autoregulation induced by the graded variations in end-tidal carbon
      dioxide.
AB  - The transient hyperemic response (THR) in the middle cerebral artery (MCA) after
      the release of brief compression of the ipsilateral common carotid artery has
      been used to study cerebral autoregulation. We conducted the present study to
      evaluate the reliability of THR to detect changes in cerebral autoregulation
      induced by graded variations in PETCO2. Seven healthy adult volunteers were
      recruited. Fifteen THR tests were performed on every volunteer: three at baseline
      PETCO2, three each at PETCO2 of 7.5 mm Hg and 15 mm Hg above the baseline, and
      then three each at PETCO2 of 7.5 mm Hg and 15 mm Hg below the baseline. Transient
      hyperemic response ratio (THRR) and strength of autoregulation (SA) were
      calculated using established formulae. Both THRR and SA were highly sensitive
      (96%) in detecting the changes in cerebral autoregulation induced by graded
      changes in PETCO2. The within-individual variability of SA was significantly
      smaller than that of THRR at all levels of PETCO2. IMPLICATIONS: This study
      demonstrates the reliability of the THR test, when used for repetitive
      measurements, in detecting changes in cerebral autoregulation induced by graded
      changes in PETCO2. This test may provide a simple and noninvasive method of
      evaluating changes in cerebral autoregulation within an individual.

PMID- 9768781
TI  - The effect of hyperventilation and hyperoxia on cerebral venous oxygen saturation
      in patients with traumatic brain injury.
AB  - Eighteen head-injured patients undergoing hyperventilation were studied for
      changes in jugular venous oxygen saturation (SjvO2) and arteriovenous oxygen
      content difference (AVDO2) in response to changes in PaO2 and PaCO2. SjvO2
      decreased significantly from 66% +/- 3% to 56% +/- 3% (mean +/- SD) when PaCO2
      decreased from 30 to 25 mm Hg at a PaO2 of 100-150 mm Hg. SjvO2 values returned
      to baseline (66% +/- 2%) when PaCO2 was restored to 30 mm Hg. Repetition of the
      study at a PaO2 of 200-250 mm Hg produced a similar pattern. However, SjvO2
      values were significantly greater with PaO2 within the range of 200-250 mm Hg
      (77% +/- 4% and 64% +/- 3%) than SjvO2 measured at a PaO2 of 100-150 mm Hg at
      PaCO2 values of both 30 and 25 mm Hg. AVDO2 also improved with a PaO2 of 200-250
      mm Hg at each PaCO2 (P < 0.001). In conclusion, decreases in SjvO2 associated
      with decreases in PaCO2 may be offset by increasing PaO2. IMPLICATIONS: The
      adequacy of cerebral oxygenation can be estimated in head-injured patients by
      monitoring jugular bulb oxygen saturation and the arteriovenous oxygenation
      content difference. Increasing the partial pressure of arterial oxygen above
      normal offset deleterious effects of hyperventilation on jugular bulb oxygen
      saturation and arteriovenous oxygenation content difference in head-injured
      patients.

PMID- 9768782
TI  - The effects of sevoflurane on cerebral blood flow autoregulation in rats.
AB  - In this study, we investigated the effect of sevoflurane on cerebral blood flow
      (CBF) autoregulation in rats. Twenty-four male Sprague-Dawley rats were randomly
      assigned to receive one of the following anesthetic treatments. In Group 1 (n =
      8, control) anesthesia was maintained using fentanyl (25 microg x kg(-1) x h(-1))
      and N2O/O2 (fraction of inspired oxygen 0.33). In Group 2 (n = 8) and Group 3 (n
      = 8), anesthesia was maintained using 2% sevoflurane (1 minimum alveolar
      anesthetic concentration [MAC]) and 2 MAC sevoflurane (4 vol%) in O2/air
      (fraction of inspired oxygen 0.33), respectively. Cortical CBF autoregulation was
      measured during graded hemorrhage within the mean arterial pressure (MAP) range
      of 100-30 mm Hg using laser Doppler flowmetry. CBF was constant with fentanyl/
      N2O (Group 1) and 1 MAC sevoflurane (Group 2) within the MAP range of 100-40 mm
      Hg. In Group 3 (2 MAC sevoflurane), CBF decreased as a linear function of
      hemorrhagic hypotension. These results indicate that CBF autoregulation was
      intact during 1 MAC sevoflurane. In contrast, CBF autoregulation was impaired
      with 2 MAC sevoflurane. This is probably related to a reduction of baseline
      cerebrovascular tone with higher concentrations of sevoflurane, which results in
      a decreased capacity of autoregulatory cerebrovascular dilation during
      hemorrhage. IMPLICATIONS: The purpose of the present study was to investigate the
      effect of sevoflurane on cerebral blood flow autoregulation in rats. Cerebral
      blood flow autoregulation was intact with 1 minimum alveolar anesthetic
      concentration sevoflurane but was impaired with 2 minimum alveolar anesthetic
      concentration sevoflurane.

PMID- 9768783
TI  - Increased plasma concentration of adrenomedullin in patients with subarachnoid
      hemorrhage.
AB  - Adrenomedullin (AM) is a potent hypotensive peptide originally identified in
      pheochromocytoma tissues. Impaired cardiovascular conditions, such as
      hypertension, myocardial infarction, and septic shock, stimulate production of
      AM. This study was performed to determine whether subarachnoid hemorrhage (SAH)
      altered plasma AM concentration. Plasma concentrations of AM in 17 patients with
      SAH were measured for 2 wk after the onset of SAH by AM-specific
      radioimmunoassay. Plasma concentrations of AM were increased in patients with SAH
      throughout the study period, compared with those in control subjects. Plasma
      concentrations of AM in patients classified as Hunt and Kosnik grade III or IV
      were significantly higher than those classified as Hunt and Kosnik grade I or II
      on the day of and the day after the onset of SAH. However, plasma concentrations
      of AM were unaffected by angiographic vasospasm. These findings suggest that
      plasma concentrations of AM are increased in patients with SAH and may reflect
      the severity of SAH. IMPLICATIONS: Adrenomedullin has been reported to affect the
      cerebral circulation. This study was performed to determine whether subarachnoid
      hemorrhage, a typical cerebrovascular disorder, altered plasma adrenomedullin
      concentrations. We found that plasma adrenomedullin concentrations increased in
      patients with subarachnoid hemorrhage, although no relationship was found between
      plasma adrenomedullin concentration and angiographic vasospasm. Plasma
      adrenomedullin concentration may reflect the severity of hemorrhage.

PMID- 9768785
TI  - Infraclavicular brachial plexus block: parasagittal anatomy important to the
      coracoid technique.
AB  - Infraclavicular brachial plexus block is a technique well suited to prolonged
      continuous catheter use. We used a coracoid approach to this block to create an
      easily understood technique. We reviewed the magnetic resonance images of the
      brachial plexus from 20 male and 20 female patients. Using scout films, the
      parasagittal section 2 cm medial to the coracoid process was identified. Along
      this oblique section, we located a point approximately 2 cm caudad to the
      coracoid process on the skin of the anterior chest wall. From this point, we
      determined simulated needle direction to contact the neurovascular bundle and
      measured depth. At the skin entry site, the direct posterior insertion of a
      needle will make contact with the cords of the brachial plexus where they
      surround the second part of the axillary artery in all images. The mean (range)
      distance (depth along the needle shaft) from the skin to the anterior wall of the
      axillary artery was 4.24 +/- 1.49 cm (2.25-7.75 cm) in men and 4.01 +/- 1.29 cm
      (2.25-6.5 cm) in women. Hopefully, this study will facilitate the use of this
      block. IMPLICATIONS: We sought a consistent, palpable landmark for facilitation
      of the infraclavicular brachial plexus block. We used magnetic resonance images
      of the brachial plexus to determine the depth and needle orientation needed to
      contact the brachial plexus. Hopefully, this study will facilitate the use of
      this block.

PMID- 9768784
TI  - The tocolytic effect of catecholamines in the gravid rat uterus.
AB  - Maternal catecholamines increase dramatically in labor because of pain and
      emotional stress. Because the uterus is richly endowed with both alpha- and beta
      adrenergic receptors, catecholamines could alter uterine activity. We assessed
      the effect of clinically encountered concentrations of these catecholamines on
      uterine activity and modeled the effect of the abrupt reduction in circulating
      epinephrine that occurs during effective labor analgesia. Term pregnant rat uteri
      were excised, and cross-sectional rings were mounted for isometric force
      recording. Log concentration-response curves for epinephrine, norepinephrine, and
      their combination on uterine activity were constructed from 10(-12) to 10(-6) M.
      Catecholamine responses were repeated in the presence of phentolamine, an alpha
      adrenergic blocker or propranolol, a beta-adrenergic blocker. The abilities of
      oxytocin and of washout of catecholamines to reverse catecholamine-induced
      changes in uterine activity were also assessed. Epinephrine caused dose-dependent
      reductions in uterine activity, blocked by propranolol. Epinephrine
      concentrations in the clinical range(10(-9) to 10(-8) M; 100-1000 pg/mL)
      decreased uterine activity to 49.6% +/- 6.6% (mean +/- SE) of control.
      Norepinephrine caused a dose-dependent increase in uterine activity, which was
      blocked by phentolamine. In the clinical range (10(-8) M), uterine activity was
      139.2% +/- 13.40% of control. The combination of both catecholamines, however,
      was nearly as tocolytic as epinephrine alone. Oxytocin antagonized catecholamine
      induced tocolysis, and washout of epinephrine or both catecholamines increased
      uterine activity. We conclude that mixed catecholamines are significantly
      tocolytic at concentrations encountered in laboring women. In this in vitro
      model, reduction in epinephrine concentration, comparable to that which occurs
      during effective analgesia, significantly increases uterine activity.
      IMPLICATIONS: Maternal catecholamines increase in labor, but epinephrine
      decreases dramatically after regional analgesia. In this study, we found that
      norepinephrine and epinephrine together decrease uterine contractile activity and
      that decreased epinephrine causes significantly increased uterine activity.

PMID- 9768786
TI  - Spinal anesthesia increases pulmonary responsiveness to methacholine in guinea
      pigs.
AB  - It has been postulated that regional anesthesia, when feasible, is the best
      anesthetic approach in asthmatic patients. However, there are reports of severe
      bronchospasm during regional anesthesia. In the present study, we developed an
      experimental model of spinal (subarachnoid) anesthesia in guinea pigs and studied
      respiratory system responsiveness to aerosolized methacholine. The animals
      received sodium pentobarbital (50 mg/kg intraperitoneally), a tracheotomy, and
      mechanical ventilation. Four groups of animals were studied: guinea pigs that
      received spinal anesthesia with lidocaine (500 microL of 2% solution) (n = 7);
      guinea pigs that received spinal administration of isotonic sodium chloride
      solution (500 microL) (n = 7); guinea pigs that received an intraperitoneal
      injection of lidocaine (500 microL of 2% solution) (n = 6); and control guinea
      pigs (n = 7). The concentration of methacholine chloride that resulted in 50% of
      the maximal value of respiratory system elastance was lower in guinea pigs that
      received spinal anesthesia compared with the other three groups (P < 0.005 for
      control group, P < 0.01 for spinal saline group, and P < 0.05 for intraperitoneal
      lidocaine group). Our results suggest that spinal anesthesia results in an
      increase in pulmonary responsiveness to bronchoconstrictive stimuli.
      IMPLICATIONS: Regional anesthesia has been considered the best anesthetic
      approach in asthmatic patients, although there are reports of severe
      bronchospasm. We developed an experimental model of spinal anesthesia with
      lidocaine in guinea pigs and studied respiratory responsiveness to methacholine,
      a bronchoactive agonist. Spinal anesthesia resulted in an increase in respiratory
      responsiveness.

PMID- 9768788
TI  - Fundamental properties of local anesthetics: half-maximal blocking concentrations
      for tonic block of Na+ and K+ channels in peripheral nerve.
AB  - Local anesthetics suppress excitability by interfering with ion channel function.
      Ensheathment of peripheral nerve fibers, however, impedes diffusion of drugs to
      the ion channels and may influence the evaluation of local anesthetic potencies.
      Investigating ion channels in excised membrane patches avoids these diffusion
      barriers. We investigated the effect of local anesthetics with voltage-dependent
      Na+ and K+ channels in enzymatically dissociated sciatic nerve fibers of Xenopus
      laevis using the patch clamp method. The outside-out configuration was chosen to
      apply drugs to the external face of the membrane. Local anesthetics reversibly
      blocked the transient Na+ inward current, as well as the steady-state K+ outward
      current. Half-maximal tonic inhibiting concentrations (IC50), as obtained from
      concentration-effect curves for Na+ current block were: tetracaine 0.7 microM,
      etidocaine 18 microM, bupivacaine 27 microM, procaine 60 microM, mepivacaine 149
      microM, and lidocaine 204 microM. The values for voltage-dependent K+ current
      block were: bupivacaine 92 microM, etidocaine 176 microM, tetracaine 946 microM,
      lidocaine 1118 microM, mepivacaine 2305 microM, and procaine 6302 microM.
      Correlation of potencies with octanol:buffer partition coefficients (logP0)
      revealed that ester-bound local anesthetics were more potent in blocking Na+
      channels than amide drugs. Within these groups, lipophilicity governed local
      anesthetic potency. We conclude that local anesthetic action on peripheral nerve
      ion channels is mediated via lipophilic drug-channel interactions. IMPLICATIONS:
      Half-maximal blocking concentrations of commonly used local anesthetics for Na+
      and K+ channel block were determined on small membrane patches of peripheral
      nerve fibers. Because drugs can directly diffuse to the ion channel in this
      model, these data result from direct interactions of the drugs with ion channels.

PMID- 9768787
TI  - The advantages of the lateral decubitus position after spinal anesthesia with
      hyperbaric tetracaine.
AB  - We investigated the effects of lateral decubitus positioning after spinal
      anesthesia with hyperbaric tetracaine on the spread of sensory blockade and
      hemodynamic variables. One hundred ASA physical status I or II patients scheduled
      for elective surgery to the lower limb received spinal anesthesia at a rate of
      approximately 0.1 mL/s using 0.5% tetracaine in 7.5% glucose with 0.125%
      phenylephrine in the lateral decubitus position with the operated side dependent.
      They were randomly divided into three groups: patients in Group I were placed
      supine immediately after spinal injection; those in Group II remained in the
      lateral position for 10 min before being turned supine; those in Group III were
      kept in the lateral position for 20 min then turned supine. Neural block was
      assessed by cold, pinprick, and touch sensation, and a modified Bromage scale.
      Hemodynamic variables included blood pressure, heart rate, and the use of
      ephedrine for the treatment of hypotension. The median (10th, 90th percentiles)
      peak dermatomal level to pinprick on the dependent side in Group III was T8 (T11,
      T5), which was significantly lower than that in Groups I and II, which extended
      to T4 (T9, T3) and T5 (T10, T2), respectively (P < 0.05). The difference in the
      maximal cephalad spread of sensory blockade between both sides in Group III was
      only one dermatome but was statistically significant (P < 0.05); in contrast,
      there was no significant difference in the maximal sensory level between both
      sides in Groups I and II. The use of ephedrine for the treatment of hypotension
      was significantly less frequent in Group III than the other groups. We conclude
      that keeping a patient in the lateral decubitus position for 20 min after
      hyperbaric tetracaine spinal anesthesia maintains preferential anesthetic
      distribution to the dependent side. Despite small differences between the two
      sides, the restricted spread of blockade and less hemodynamic variability may be
      clinically advantageous. IMPLICATIONS: The effects of posture on the spread of
      hyperbaric spinal anesthesia have not been adequately investigated. The results
      of the present study suggest an advantage of prolonged lateral decubitus
      positioning after intrathecal hyperbaric tetracaine.

PMID- 9768789
TI  - Postoperative analgesic effects of three demand-dose sizes of fentanyl
      administered by patient-controlled analgesia.
AB  - Many studies have demonstrated the postoperative analgesic efficacy of fentanyl
      delivered i.v. by patient-controlled analgesia (PCA) devices at demand doses
      ranging from 10 to 50 microg, but none has sought to define the optimal fentanyl
      PCA dose. In this randomized, double-blind, multicenter study, we compared the
      safety and efficacy of three administered demand-dose sizes of fentanyl (20, 40,
      and 60 microg) in 150 patients after major surgery. Efficacy was dose-dependent;
      positive response rates (i.e., a global assessment score of "very good" or
      "excellent" and the absence of severe opioid adverse effects) were 42%, 52%, and
      68% for the 20, 40, and 60 microg demand-dose groups, respectively, and were
      significantly higher in the 60 microg demand-dose group. The number of doses
      administered and missed attempts were significantly smaller in the 40 and 60
      microg demand-dose groups compared with the 20 microg demand-dose group. This
      suggests that the 20 microg demand dose provided inadequate pain relief. Adverse
      respiratory events were more frequent and mean respiratory rates were
      significantly slower with the 60 microg demand dose, compared with the 20 or 40
      microg demand doses. These results indicate that, of these three doses, the 40
      microg demand dose was optimal for fentanyl PCA management of moderate to severe
      pain after major surgery. IMPLICATIONS: The postoperative analgesic efficacy of
      fentanyl delivered i.v. by patient-controlled analgesia devices has been
      demonstrated for demand doses ranging from 10 to 50 microg, but the optimal
      fentanyl dose remains unknown. In this randomized, double-blind study, we
      compared three demand dose sizes of fentanyl (20, 40, and 60 microg) and found
      that the 40 microg demand dose was the most appropriate for fentanyl patient
      controlled analgesia management of postoperative pain.

PMID- 9768790
TI  - Cryoanalgesia: effect on postherniorrhaphy pain.
AB  - Cryoanalgesia versus sham treatment was applied to the ilioinguinal and
      iliohypogastric nerves after mesh repair of an inguinal hernia under local
      anesthesia in 48 male patients in a prospective, randomized, and observer- and
      patient-blinded trial. Pain was scored daily during rest, while coughing, and
      during mobilization to the sitting position for 1 wk and weekly for 8 wk on a
      four-point verbal rank scale. Use of supplementary analgesics and sensory
      disturbances were recorded. Assessments were made for allodynia, hyperalgesia,
      and mechanical pain detection thresholds 8 wk postoperatively. Cumulative pain
      scores for the first postoperative week were equal in the two groups, as was the
      use of analgesics. Eight weeks postoperatively, three cases of hyperalgesia to
      pinprick were detected in the cryoanalgesia group, and 10 patients in the
      cryoanalgesia group versus 5 in the sham-treatment group reported disturbed
      sensibility. We conclude that cryoanalgesia of the iliohypogastrical and
      ilioinguinal nerve does not decrease postherniorrhaphy pain. IMPLICATIONS: Does
      freezing of sensory nerves in the groin reduce pain after hernia repair? Extreme
      cold (-60 degrees C) was applied in a double-blind, randomized study. No
      difference in pain scores was found. Sensory disturbances were seen in treatment
      and control patients. Freezing cannot be recommended for pain relief after hernia
      repair.

PMID- 9768791
TI  - Posttreatment with propofol terminates lidocaine-induced epileptiform
      electroencephalogram activity in rabbits: effects on cerebrospinal fluid
      dynamics.
AB  - There are no controlled studies to determine whether propofol given after the
      onset of lidocaine-induced seizures (posttreatment) stops lidocaine-induced
      seizures. In this study, we determined whether posttreatment with propofol
      abolishes lidocaine-induced epileptiform electroencephalogram (EEG) activity as
      effectively as does midazolam, and cerebrospinal fluid (CSF) dynamics during
      lidocaine-induced epileptiform EEG activity and its treatment. EEG activity and
      CSF dynamics were determined in two groups of anesthetized rabbits at each of
      four experimental conditions: baseline, lidocaine-induced epileptiform activity,
      treatment with midazolam (n = 6) or propofol (n = 6), and return to baseline. The
      analog EEG signal was converted into a set of digital parameters using aperiodic
      analysis, and CSF dynamics were determined using ventriculocistemal perfusion.
      Propofol (3.8 +/- 1.3 mg/kg) stopped epileptiform activity, as did midazolam (2.0
      +/- 1.7 mg/kg). The rates of CSF formation or reabsorption and resistances to CSF
      reabsorption or flow at the arachnoid villi did not differ among conditions or
      between groups. Our results indicate that propofol and midazolam both terminate
      epileptiform activity without changing CSF dynamics. IMPLICATIONS: Propofol may
      be an alternative to benzodiazepines for treating lidocaine-induced epileptiform
      electroencephalogram activity in patients.

PMID- 9768792
TI  - Comparison of patient-controlled epidural analgesia with and without background
      infusion after gastrectomy.
AB  - To assess the analgesic efficacy and side effects of concurrent infusion in
      patient-controlled epidural analgesia (PCEA) after upper abdominal surgery, 40
      patients undergoing elective gastrectomy under general anesthesia were allocated
      to two groups in this randomized, double-blind study: one received a 2.5-mL
      incremental bolus in a solution of 0.2% bupivacaine and 10 microg/mL fentanyl,
      and the other received the same bolus dose plus a 2.5-mL/h infusion of the same
      solution. The number of demands was smaller (P < 0.001) in the PCEA plus infusion
      group than in the PCEA alone group during the 48-h postoperative period. The
      average hourly fentanyl and bupivacaine doses were larger (P < 0.0001) in the
      PCEA plus infusion group than in the PCEA alone group. Visual analog scale pain
      scores on coughing in the PCEA plus infusion group were lower than in the PCEA
      alone group (P < 0.05). There was a greater incidence of pruritus in the PCEA
      plus infusion group (P < 0.05), but no serious side effects were observed in
      either group. In conclusion, a background infusion in PCEA with a mixture of
      fentanyl and bupivacaine decreases the incidence of postoperative pain and
      reduces the degree of pain associated with coughing without serious side effects
      after gastrectomy. IMPLICATIONS: A background infusion in patient-controlled
      epidural analgesia with a mixture of fentanyl and bupivacaine decreased the
      incidence of postoperative pain and reduced the degree of the pain associated
      with coughing without serious side effects in this randomized, double-blind study
      after gastrectomy.

PMID- 9768793
TI  - Percutaneous electrical nerve stimulation: an alternative to antiviral drugs for
      acute herpes zoster.

PMID- 9768794
TI  - Jet ventilation in upper airway obstruction: description and model lung testing
      of a new jetting device.
AB  - Patients with critical upper airway stenosis require a tracheotomy for corrective
      surgery. We describe a new transtracheal device that permits safe ventilation of
      these patients without tracheotomy. It is based on a coaxial bicannular design
      that allows "push-pull" ventilation by jetting gas through the inner cannula and
      applying suction through the outer cannula. It further allows monitoring of
      airway pressure, tidal volume, and end-tidal CO2. The device was placed in the
      "trachea" of an artificial lung, and the preparation was made airtight by sealing
      the proximal end of the trachea. Tidal volumes and their associated pressures
      were measured simultaneously at different parts of the airway at several lung
      compliances and airway resistance settings while varying the jet and suction
      pressures. A large range of tidal volumes was achieved at safe airway pressures
      using clinically relevant airway resistance and lung compliance settings. Airway
      pressures measured through the device correlated well with pressures measured
      directly in the airways at the same time. Tidal volumes, measured through a
      Wright respirometer in the suction line, exceeded actual values at high suction
      settings and decreased below actual values at low suction settings. This new form
      of jet ventilation allowed efficient ventilation of the artificial lung with a
      totally occluded upper airway. IMPLICATIONS: Tracheotomy is required for surgery
      to relieve stridor because gas forced into the trachea at high pressures through
      a percutaneously placed needle (jetting) cannot be exhaled quickly enough for
      respiration. We describe a device that allows jetting in the stridorous patient
      by actively assisting expiration, thereby eliminating the tracheotomy
      requirement.

PMID- 9768795
TI  - A comparison of the disposable versus the reusable laryngeal mask airway in
      paralyzed adult patients.
AB  - A disposable (polyvinyl chloride) laryngeal mask airway (LMA) with dimensions
      identical to, but physical properties different from (stiffer tube/thicker cuff),
      the reusable (silicone) LMA has recently become available. We performed a
      randomized, cross-over study of 60 paralyzed, anesthetized patients to test the
      hypothesis that the use of these devices was different in terms of ease of
      insertion, airway sealing pressure, fiberoptic position, and changes in intracuff
      pressure during N2O anesthesia. We also tested the hypothesis that the airway
      sealing pressure of the LMA is suboptimal if the cuff is inflated to a high
      intracuff pressure. Both the devices were inserted into each patient in random
      order, and their performance was assessed at two intracuff pressures (60 and 180
      cm H2O) by a blind observer. Subsequently, intracuff pressures were measured
      during N2O anesthesia for the second device. Ease of insertion was similar: there
      was no difference in first attempt success rates (97% vs 98%) and insertion times
      (15 vs 13 s) for the disposable and reusable LMA, respectively. There were no
      differences in airway sealing pressure or fiberoptic position. Airway sealing
      pressure was significantly higher at 60 cm H2O intracuff pressure compared with
      the airway sealing pressure at 180 cm H2O for both devices (P < 0.02). During N2O
      anesthesia, the intracuff pressure remained stable for the disposable LMA but
      increased significantly for the reusable LMA. We conclude that the disposable and
      reusable LMAs perform similarly in paralyzed adult patients, but that the
      disposable LMA has more stable intracuff pressures during N2O anesthesia.
      Inflation of the LMA to high intracuff pressures produces a suboptimal seal.
      IMPLICATIONS: This randomized, single-blind, within-patient study of 60 adult
      patients shows that the disposable (polyvinyl chloride) and reusable (silicone)
      laryngeal mask airways perform similarly, but that the disposable laryngeal mask
      airway has more stable intracuff pressures during N2O anesthesia. Inflation of
      either device to high intracuff pressures produces a suboptimal seal.

PMID- 9768796
TI  - The effects of the lateral position on cardiopulmonary function during
      laparoscopic urological surgery.
AB  - Laparoscopic urological surgery is usually performed transperitoneally with
      retroperitoneal insufflation of carbon dioxide (CO2) in the lateral position. We
      studied whether a difference in the side of lateral position affected hemodynamic
      and pulmonary functions during pneumoperitoneum. Fifteen patients (eight in the
      right and seven in the left lateral position) undergoing elective laparoscopic
      urological surgery were studied under general anesthesia. Hemodynamic variables
      and blood gas data were recorded. Before insufflation, mean arterial pressure
      (MAP), mean pulmonary arterial pressure (MPAP), central venous pressure (CVP),
      and pulmonary capillary wedge pressure (PCWP) in the right lateral position were
      higher than those in the left lateral position. Pneumoperitoneum increased MAP,
      MPAP, CVP, PCWP, and cardiac index but decreased systemic vascular resistance in
      the right lateral position. Similar changes occurred during pneumoperitoneum in
      the left lateral position, but the changes were less than those in the right
      lateral position. The respiratory index (PaO2/PAO2), intrapulmonary shunt, and
      SpO2 did not change during pneumoperitoneum in either lateral position. Changing
      the side of the lateral position affected hemodynamic function but did not affect
      pulmonary oxygenation during pneumoperitoneum. IMPLICATIONS: The right and left
      lateral positions produced different hemodynamic changes during laparoscopic
      urological surgery. The increases in preload and cardiac index and the decrease
      in systemic vascular resistance were greater in the right than in the left
      lateral position. Respiratory changes were not affected differently between the
      right and left lateral positions.

PMID- 9768797
TI  - Single-dose tropisetron for preventing postoperative nausea and vomiting after
      breast surgery.
AB  - In this randomized, double-blind, placebo-controlled study, we compared the
      efficacy of tropisetron 5 mg with tropisetron 2 mg for the prevention of
      postoperative nausea and vomiting (PONV) after breast surgery. One hundred forty
      eight female patients were randomized to receive either tropisetron 5 mg (n =
      49), tropisetron 2 mg (n = 49), or saline (n = 50) before the induction of
      anesthesia with thiopental and morphine. Anesthesia was maintained with nitrous
      oxide and isoflurane. Postoperative analgesia was provided by patient-controlled
      analgesia with i.v. morphine. The incidence of PONV, the pain score, and the
      analgesic requirement were recorded for 48 h. There was no difference among
      groups in patient characteristics, risk factors for PONV, morphine consumption,
      or side effects. During the first 6 h postoperatively, the incidence of PONV
      after tropisetron 2 mg and 5 mg were similar and were superior to placebo (P <
      0.001). After 6 h, the incidence of PONV increased significantly in patients who
      had received tropisetron 2 mg (P = 0.01) and was greater than that in patients
      who had received tropisetron 5 mg (P = 0.001). We conclude that single-dose
      tropisetron 5 mg is more effective than tropisetron 2 mg in the prevention of
      PONV after breast surgery. IMPLICATIONS: Breast surgery is associated with a high
      incidence of postoperative nausea and vomiting. A single dose of i.v. tropisetron
      5 mg is well tolerated and decreases the number of vomiting and nausea episodes
      after surgery.

PMID- 9768798
TI  - Neuromuscular effects of rocuronium during sevoflurane, isoflurane, and
      intravenous anesthesia.
AB  - The potency and time course of action of rocuronium were studied in patients
      anesthetized with 66% nitrous oxide in oxygen and 1.5 minimum alveolar anesthetic
      concentration of sevoflurane or isoflurane, or a propofol infusion. Potency was
      estimated by using the single-bolus technique. Neuromuscular block was measured
      by stimulation of the ulnar nerve and by recording the force of contraction of
      the adductor pollicis muscle. The mean (95% confidence limits) of the 50% and 95%
      effective doses were estimated tobe 142 (129-157) and 265 (233-301) microg/ kg,
      165 (146-187) and 324 (265-396) microg/kg, and 183 (163-207) and 398 (316-502)
      microg/kg during sevoflurane, isoflurane, and propofol anesthesia, respectively
      (P < 0.05 for sevoflurane versus propofol). The mean +/- SD times to onset of
      maximal block after rocuronium 0.6 mg/kg were 0.96 +/- 0.16, 0.90 +/- 0.16, and
      1.02 +/- 0.15 min during sevoflurane, isoflurane, and propofol anesthesia,
      respectively. The respective times to recovery of the first response in the train
      of-four (TOF) stimulation (T1) to 25% and 90% were 45 +/- 13.1 and 83 +/- 29.3
      min, 35 +/- 6.1 and 56 +/- 15.9 min, and 35 +/- 9.2 and 55 +/- 19.4 min. The
      times to recovery of the TOF ratio to 0.8 were 103 +/- 30.7, 69 +/- 20.4, and 62
      +/- 21.1 min, and the 25%-75% recovery indices were 26 +/- 11.7, 12 +/- 5.0, and
      14 +/- 6.9 min, respectively. There were no differences among groups in the times
      for onset of action or to recovery of T1 to 25%. However, the times for recovery
      of T1 to 90%, TOF ratio to 0.8, and recovery index in the sevoflurane group were
      all significantly longer compared with the other two groups (P < 0.05, < 0.01,
      and < 0.01, respectively). We conclude that the effects of rocuronium, especially
      duration of action, are significantly enhanced during sevoflurane compared with
      isoflurane and propofol anesthesia. IMPLICATIONS: In routine clinical use, the
      effects of rocuronium are enhanced by sevoflurane, in comparison with isoflurane
      and propofol anesthesia, and the recovery is slower. Particular attention should
      be paid to monitoring of neuromuscular block during sevoflurane anesthesia.

PMID- 9768799
TI  - The analgesic potency of dexmedetomidine is enhanced after nerve injury: a
      possible role for peripheral alpha2-adrenoceptors.
AB  - This study investigated the analgesic potency and site of action of systemic
      dexmedetomidine, a selective alpha2-adrenoceptor (alpha2AR) agonist, in normal
      and neuropathic rats. Ligation of the L5-6 spinal nerves produced a chronic
      mechanical and thermal neuropathic hyperalgesia in rats. von Frey fibers and a
      thermoelectric Peltier device were used to measure mechanical and heat withdrawal
      thresholds over the hindpaw. Systemic dexmedetomidine dose-dependently increased
      the mechanical and thermal thresholds in the control animals (50% effective dose
      [ED50] 144 and 180 microg/kg intraperitoneally [i.p.], respectively). Neuropathic
      animals responded to much smaller doses of dexmedetomidine with mechanical and
      thermal ED50 values of 52 and 29 microg/kg i.p., respectively. There was no
      difference between the control and neuropathic animals with respect to
      dexmedetomidine-evoked sedation, as determined by decreased grid crossings in an
      open-field activity chamber (ED50 12 and 9 microg/kg i.p., respectively).
      Atipamezole, a selective alpha2AR antagonist, blocked the analgesic and sedative
      actions of dexmedetomidine inboth the neuropathic and control animals. However, L
      659,066, a peripherally restricted alpha2AR antagonist, could only block the
      analgesic actions of dexmedetomidine in the neuropathic rats, with no effect in
      control animals. In conclusion, nerve injury enhanced the analgesic but not the
      sedative potency of systemic dexmedetomidine and may have shifted the site of
      alpha2 analgesic action to outside the blood-brain barrier. IMPLICATIONS: We
      tested the analgesic efficacy of the alpha2 agonist dexmedetomidine in normal and
      nerve-injured rats. The analgesic potency of dexmedetomidine was enhanced after
      nerve injury with a site of action outside the central nervous system.
      Peripherally restricted alpha2 agonists may be useful in the management of
      neuropathic pain.

PMID- 9768800
TI  - The effect of the interaction of propofol and alfentanil on recall, loss of
      consciousness, and the Bispectral Index.
AB  - The Bispectral Index (BIS) correlates well with the level of consciousness with
      single anesthetic drugs. We studied the effect of the interaction of propofol
      with alfentanil on propofol concentration and BIS associated with 50% probability
      of loss of consciousness and lack of recall (Cp50 and BIS50, respectively). We
      studied 40 consenting volunteers at two institutions who were randomly assigned
      to receive stepped increases of propofol (10 subjects at each site), propofol
      plus alfentanil 50 ng/mL (10 subjects at Emory site), or propofol plus alfentanil
      100 ng/mL (10 subjects at Duke site) by using a target-controlled infusion
      device. Measures of sedation, BIS, deltaBIS (absolute change of BIS after a
      painful stimulus), memory, and drug concentration were obtained at each target
      drug concentration. The relation among BIS, measured drug concentration, sedation
      score, and presence or absence of recall was determined by linear and logistic
      regression for different drug regimens, and the prediction probability (Pk) was
      calculated. The addition of alfentanil in increasing doses did not significantly
      affect the BIS50 and propofol Cp50 values for loss of consciousness and lack of
      recall. DeltaBIS was significantly decreased by both an increase in the
      concentration of propofol and the presence of alfentanil. The Pk for BIS was
      >0.93 with all drug regimens, better than those of the target and measured
      propofol concentrations. We conclude that BIS correlated well with the hypnotic
      component of anesthesia independent of the presence of an opioid. Moreover, the
      level of consciousness, and, therefore, the BIS index, is affected by a painful
      stimulus, and this response is ablated either by opioids or increasing propofol
      concentration. IMPLICATIONS: In volunteers, the sedation and changes in memory
      function produced by propofol correlated well with changes in the Bispectral
      Index. This relationship was not altered by the addition of an analgesic
      (alfentanil). However, in moderately sedated patients who received a painful
      stimulus, the Bispectral Index increased, but this response was blocked by the
      analgesic or increasing propofol concentrations.

PMID- 9768801
TI  - Pulmonary vasodilation by ketamine is mediated in part by L-type calcium
      channels.
AB  - We studied the effects of ketamine in the isolated rat lung under conditions of
      increased pulmonary arterial pressure using the thromboxane A2 mimic, U46619, and
      in response to ventilatory hypoxia. Ketamine caused dose-dependent vasodilation,
      and possible mechanisms were evaluated using verapamil, meclofenamate, N(omega)-L
      nitro-L-arginine benzyl ester (an inhibitor of nitric oxide synthase), and U
      38883A (an ATP-sensitive potassium channel antagonist) in the isolated blood
      perfused rat lung. Under increased tone conditions, N(omega)-L-nitro-L-arginine
      benzyl ester, meclofenamate, and U-38883A had no significant effect in
      attenuating ketamine-induced vasodilator responses. In a final series of
      experiments, verapamil significantly attenuated ketamine-induced vasodilator
      responses. These data suggest that ketamine has significant vasodilator activity
      in the pulmonary vascular bed of the rat, which seems to be mediated by an L-type
      calcium channel-sensitive pathway. These responses are not mediated or modulated
      by the release of nitric oxide, the activation of K+ ATP channels, or the release
      of vasodilator cyclooxygenase products. IMPLICATIONS: In this study, we examined
      the mechanism of the vasodilator effects of ketamine in the blood-perfused rat
      lung. The results of the present study suggest that ketamine-induced vasodilator
      responses are mediated by an L-type calcium channel-sensitive pathway.

PMID- 9768802
TI  - Rat strain minimally influences anesthetic and convulsant requirements of inhaled
      compounds in rats.
AB  - We assessed the effect of rat strain on susceptibility to anesthesia and
      convulsions produced by inhaled compounds. We determined the minimum alveolar
      anesthetic concentration (MAC) of desflurane and nitrous oxide, and the
      convulsive 50% effective dose (ED50) of 1,2-dichlorohexafluorocyclobutane,
      flurothyl, and difluoromethyl-1-chlorotetrafluoroethyl ether in five strains
      (three inbred [Long Evans, Sprague-Dawley, and Wistar] and two outbred [Fischer
      and Brown Norway]). Strain had slight effects on anesthetic potency, the strains
      with the highest MAC values (Long Evans and Brown Norway) having values < or =28%
      greater than the strains with the lowest values (Sprague Dawley and Wistar). MAC
      for nitrous oxide correlated directly with MAC for desflurane as a function of
      strain. MAC for either desflurane or nitrous oxide correlated inversely with the
      convulsive ED50 of 1,2-dichlorohexafluorocyclobutane, but correlated poorly (and
      directly) with the convulsive ED50 of the remaining compounds. Convulsivity
      varied little as a function of strain (greatest difference 21%) and did not vary
      consistently as a function of strain. No consistent difference was seen between
      inbred versus outbred strains. IMPLICATIONS: Rat strain has a minimal effect on
      the potency of inhaled anesthetics or the convulsant activity of inhaled
      compounds. It seems that the sites acted on by inhaled compounds to produce
      anesthesia and convulsions are conserved across common rat strains.

PMID- 9768803
TI  - The interaction of eltanolone and fentanyl with special reference to logistic
      regression analysis.
AB  - We investigated whether fentanyl decreases the serum concentrations of the
      steroid anesthetic eltanolone effective in producing loss of consciousness in 50%
      of patients (EC50induction) and in preventing movement at skin incision in 50% of
      patients (EC50incision). For anesthetic induction, patients received effect-site
      target concentrations of fentanyl 0.0, 1.5, 3.0, or 4.5 ng/mL and eltanolone 500,
      750, 1000, or 1200 ng/mL. Loss of response to verbal command was assessed after
      10 min. For incision, patients received effect-site target concentrations of
      fentanyl 0.5,1.5, 3.0, or 4.5 ng/mL and eltanolone 547-2926 ng/mL. Movement at
      incision was assessed at least 10 min after new targets were entered. Probability
      of loss of consciousness and of movement versus arterial serum concentration
      combinations were analyzed by logistic regression. Dixon up-down analysis was
      used to estimate ET50incision effective target concentration combinations. In the
      absence of fentanyl, anesthesia was induced in only 1 of 12 patients, which
      suggests that the EC50induction is >1500 ng/mL at fentanyl 0.0 ng/mL. With
      fentanyl (38 patients), eltanolone EC50induction was independent of fentanyl
      concentration, calculated as 628 ng/mL. For the incision phase (52 patients),
      logistic regression failed to generate a valid model. Dixon analysis (43
      patients) produced an eltanolone ET50incision of 2288 ng/mL at fentanyl targets
      of 0.5 ng/mL, 754 ng/mL at 1.5 ng/mL, 735 ng/mL at 3.0 ng/mL, and 645 ng/mL at
      4.5 ng/mL. Fentanyl reduced the serum concentration of eltanolone required to
      produce loss of consciousness and the target concentration of eltanolone required
      to prevent movement to skin incision. IMPLICATIONS: Fentanyl reduced the serum
      concentration of eltanolone required to produce loss of consciousness and the
      target concentration of eltanolone required to prevent movement to skin incision.
      Future interaction studies of this nature using logistic regression should model
      responses to hypnotic alone separately from responses to hypnotic-analgesic
      combinations.

PMID- 9768804
TI  - Is Helicobacter pylori infection an occupational hazard for anesthesiologists?

PMID- 9768805
TI  - Reversibility of parkinsonism-induced acute upper airway obstruction by
      benztropine therapy.

PMID- 9768806
TI  - Nonsteroidal antiinflammatory drugs during lactation.

PMID- 9768807
TI  - Use of the laryngeal mask airway as an alternative to the tracheal tube during
      ambulatory anesthesia.

PMID- 9768808
TI  - Complications of CO2 flooding the surgical field in open heart surgery: an old
      technique revisited.

PMID- 9768809
TI  - Use of a lighted stylet for tracheal intubation through the intubating laryngeal
      mask.

PMID- 9768810
TI  - "Damping" of an arterial line: an unlikely cause.

PMID- 9768811
TI  - Relief of chronic refractory hiccups with glossopharyngeal nerve block.

PMID- 9768812
TI  - Transient global amnesia: a cause for postanesthetic memory disorder.

PMID- 9768813
TI  - Torsade de pointes ventricular tachycardia during, but not necessarily caused by,
      sevoflurane anesthesia.

PMID- 9768814
TI  - Sevoflurane and torsade de pointes.

PMID- 9768815
TI  - A simple oxygen delivery system for the transportation of intubated patients.

PMID- 9768816
TI  - Asystole under hypotensive epidural anesthesia.

PMID- 9768817
TI  - Chemistry of dexrazoxane and analogues.
AB  - The bisdioxopiperazine dexrazoxane (DEX; ICRF-187) has proven to be clinically
      effective in reducing the cardiotoxicity of doxorubicin and the toxicity of other
      anthracyclines. Doxorubicin and the other anthracyclines are thought to exert
      their toxicity through iron-based oxygen free radical-induced oxidative stress on
      the relatively unprotected cardiac muscle. On hydrolysis, DEX forms a compound
      (ADR-925) similar in structure to EDTA, which, like EDTA, is a strong chelator of
      iron and other metal ions. Dexrazoxane presumably exerts its cardioprotective
      effects by either binding free or loosely bound iron, or iron complexed to
      doxorubicin, thus preventing or reducing site-specific oxygen radical production
      that damages cellular components. The hydrolysis-activation of DEX to ADR-925 can
      occur through either enzymatic or nonenzymatic routes. Iron(III)-anthracycline
      complexes are directly able to promote ring-opening hydrolysis of DEX. Both
      ferrous and ferric ions (as well as several other divalent metal ions) can
      promote the hydrolysis of the one-ring open intermediates of DEX to ADR-925,
      which suggests that these intermediates may be pharmacologically active.
      Paradoxically, the ferric complex of ADR-925 has been shown to be capable of
      being reductively activated to mediate hydroxyl radical formation. This
      observation suggests that DEX may be acting through its ability to prevent site
      specific oxygen radical damage by iron-anthracycline complexes.

PMID- 9768818
TI  - The role of iron in doxorubicin-induced cardiomyopathy.
AB  - Doxorubicin participates in a wide range of free radical reactions. The drug can
      undergo one electron reduction to the corresponding semiquinone, leading the
      generation of superoxide and hydrogen peroxide. Additionally, the drug causes the
      disappearance of cardiac glutathione peroxidase, leaving the heart with no means
      of disposing of the hydrogen peroxide thus generated. Doxorubicin also is a
      powerful iron chelator and the resultant iron-drug complex is an efficient
      catalyst of the conversion of hydrogen peroxide to the highly reactive hydroxyl
      radical. Without the drug-iron complex, little or no cardiac production of
      hydroxyl radical occurs and heart damage does not occur.

PMID- 9768819
TI  - Preclinical animal models of cardiac protection from anthracycline-induced
      cardiotoxicity.
AB  - The chronic cardiotoxic effects of anthracyclines were initially detected in
      clinical trials with daunorubicin and doxorubicin. The clinical importance of
      anthracycline-induced chronic cardiotoxicity has led to the development of
      several animal models of this syndrome. Animal species examined in detail as
      models of this cardiac toxicity include the rabbit, the normotensive and
      spontaneously hypertensive rat, the mouse, the pig, and the dog. The advantages
      and disadvantages of these animal models differ according to species: small
      animals can be used for comparative investigations of anthracycline analogues
      and/or protectors, which may be available only in limited amounts, while large
      animals can be used for studies in which evaluation of cardiac function are to be
      made. Among the various animals examined, the spontaneously hypertensive rat and
      the beagle dog are considered the most suitable small and large animal models,
      respectively, because of the reproducibility of the lesions induced by
      anthracyclines in the two species. A variety of pharmacologic agents has been
      tested for cardioprotective activity. The most successful of these agents are
      those that function as antioxidants, because they either scavenge reactive oxygen
      species or prevent their formation. The most clinically useful of these agents is
      ICRF-187 (dexrazoxane), which has been found to be cardioprotective in all animal
      models.

PMID- 9768820
TI  - Preclinical models of cardiac protection and testing for effects of dexrazoxane
      on doxorubicin antitumor effects.
AB  - The ability of dexrazoxane (DEX) to protect against doxorubicin (DOX)-induced
      cardiomyopathy has been demonstrated in mice, normotensive and hypertensive rats,
      rabbits, dogs, swine, and humans. These animal models of DOX-induced
      cardiomyopathy were found to be highly predictive of DEX activity clinically. In
      mice administered maximally tolerated doses of DOX over a period of 7 weeks, the
      optimum dose of DEX was from 10:1 to 20:1 (DEX:DOX) given from 30 minutes before
      to 15 minutes after DOX. The dose ratio required to reduce the incidence of
      moderate to severe cardiomyopathy by 90% in the mouse was more than 20:1 for DOX
      and 10:1, 5:1, and 5:1 for epirubicin, daunorubicin, and idarubicin,
      respectively. Dexrazoxane was most effective in rats when treatment commenced
      with the first and third doses of DOX, but also provided cardioprotection when
      started with the sixth of 10 doses of DOX. The cardioprotective activity of DEX
      in rats was evident for more than 6 months after completion of DOX dosing.
      Results of antitumor studies in several experimental tumor models indicate that
      DEX does not interfere with the antineoplastic activity of DOX or other antitumor
      drugs. In some case, especially cyclophosphamide, there was a markedly
      synergistic antitumor effect when combined with DEX.

PMID- 9768821
TI  - Phase I trials of dexrazoxane and other potential applications for the agent.
AB  - The clinical development of dexrazoxane (DEX; ICRF-187; Zinecard, Pharmacia and
      Upjohn, Kalamazoo, MI) was originally begun using it as an antineoplastic agent.
      It had a unique mechanism of action and activity in a variety of in vitro and in
      vivo models. Phase I trials with the agent began in January 1979. The phase I
      trials indicated that DEX could be safely administered, with leukopenia and
      thrombocytopenia being the dose-limiting toxicities, on a number of different
      schedules of administration. Some hints of antitumor activity were also noted. In
      the phase I studies it was also noted, based on the chelating abilities of DEX,
      that the compound caused marked increases in urine clearance of iron and zinc in
      patients receiving the agent. That information, plus the information being
      generated in preclinical studies that DEX could protect against the
      cardiotoxicity induced by anthracyclines (through a decrease in free radical
      formation), led to the use of DEX as a cardioprotective agent (as thoroughly
      discussed in this supplement). However, in addition to working as a
      cardioprotective agent, DEX has other potential applications that are outlined
      below and include (1) treatment of patients with acquired immunodeficiency
      syndrome-related Kaposi's sarcoma, based on its activity as an angiogenesis
      inhibitor; (2) enhancement of the effects of cisplatin, based on its ability to
      increase the antiproliferative effects of cisplatin on human ovarian cancer
      cells; (3) use for treatment of iron overload states in patients who are allergic
      to deferoxamine; (4) treatment of patients with psoriasis; (5) protection from
      hyperoxic effects on the lungs; (6) protection from bleomycin-induced pulmonary
      fibrosis; (7) attenuation of acetaminophen-induced hepatotoxicity; (8) prevention
      of mucositis; and (9) other applications. Clearly, there should be additional
      investigations to maximize the usefulness of the very interesting DEX molecule.

PMID- 9768822
TI  - Clinical pharmacology of dexrazoxane.
AB  - Dexrazoxane is a synthetic bisdiketopiperazine two-ringed compound which
      hydrolyzes to an EDTA analog. These rings undergo intracellular hydrolysis to
      form the single and double (ICRF-198) chelating forms of the compound by both
      enzymatic and non-enzymatic catalysis. These dexrazoxane metabolites are
      efficient at stripping the cations from the iron:anthracycline complex. The
      disruption of the complex prevents the oxidative damage from free radicals
      promoted by this anthracycline complex. Pharmacologic studies of single agent
      dexrazoxane (originally studied as an antineoplastic agent) demonstrates an alpha
      half-life of approximately 30 minutes and a beta half-life of 2 to 4 hours. When
      given in combination with anthracyclines (e.g. doxorubicin or epirubicin) the
      pharmacokinetics of dexrazoxane are unchanged. Additional studies of
      anthracycline metabolism when given in combination with dexrazoxane, both in
      single arm and randomized cross-over studies, have generally shown no change in
      anthracycline metabolism, including pharmacokinetic parameters of alpha, beta,
      and gamma half-lives, area-under-the-curve, or clearance. There is no
      pharmacokinetic interaction of dexrazoxane on anthracycline metabolism and,
      therefore, pharmacokinetics cannot account for the cardioprotective effects
      described for dexrazoxane.

PMID- 9768823
TI  - Adult multicenter trials using dexrazoxane to protect against cardiac toxicity.
AB  - Two large multicenter placebo controlled trials (088001 and 088006) in metastatic
      breast cancer found a significant cardioprotective effect of dexrazoxane when
      administered with doxorubicin. A delayed dose analysis found a protective effect
      even after a cumulative dose of doxorubicin of 300 mg/m2. Exploratory analysis
      combing the arms on the two studies found a cardioprotective effect of
      dexrazoxane either initially or after 300 mg/m2 when administered in patients
      older than 65 years, compared to patients receiving only placebo. Also, patients
      with an ejection fraction within 10% above the lower limit of normal were
      protected with dexrazoxane. Objective response rates were borderline
      significantly lower for patients receiving dexrazoxane. Recommendations are to
      administer dexrazoxane after 300 mg/m2.

PMID- 9768824
TI  - Overview and historical development of dexrazoxane.
AB  - Dexrazoxane prevents the dose-limiting cardiotoxicity of the anthracyclines
      without reducing their antitumor efficacy and without new adverse side effects.
      Dexrazoxane reduces the severity of gastrointestinal symptoms of the
      anthracycline containing combination doxorubicin, 5-fluorouracil,
      cyclophosphamide and most surprisingly and importantly, dexrazoxane increases the
      median survival time of advanced breast cancer responders to the doxorubicin, 5
      fluorouracil, cyclophosphamide regimen. The median survival time is doubled as
      compared to controls to nearly 3 years.

PMID- 9768825
TI  - European trials with dexrazoxane in amelioration of doxorubicin and epirubicin
      induced cardiotoxicity.
AB  - The ability of dexrazoxane (DEX) to protect against anthracycline-induced
      cardiotoxicity has been evaluated in several European studies using either
      standard or high-dose regimens. In addition, one randomized trial investigated
      the value of cardiac radioimmunoscintigraphy with indium-111 antimyosin
      monoclonal antibodies in the early detection of cardiac damage. The results of
      these trials demonstrate that DEX is able to ameliorate doxorubicin- and
      epirubicin-induced cardiotoxicity, even when high single drug doses are used. The
      cardioprotective effect of DEX has been clearly documented by both clinical and
      laboratory cardiac evaluation. The use of DEX did not add to the toxicity of the
      anthracyclines, nor was there clear evidence of an adverse impact of the agent on
      antitumor activity of the chemotherapeutic regimen. Radioimmunoscintigraphy was
      very sensitive in detecting anthracycline cardiac damage, but its specificity is
      low and it cannot be considered a primary test for guiding anthracycline
      treatment.

PMID- 9768826
TI  - Efficacy of dexrazoxane as a cardioprotective agent in patients receiving
      mitoxantrone- and daunorubicin-based chemotherapy.
AB  - Dexrazoxane (DEX) selectively blocks the development of irreversible diffuse
      myocardial toxicity induced by anthracyclines and related antitumor agents, such
      as mitoxantrone (MTX). Therefore, daunorubicin (DNR) should not be administered
      to patients with cumulative DNR doses higher than 550 to 700 mg/m2, which we used
      for remission induction and consolidation therapy in patients with acute myeloid
      leukemia (AML). To administer further doses of anthracyclines without risks in
      seven relapsed AML patients and in one patient with impaired heart functions
      receiving consolidation therapy, we used DEX as a cardioprotective agent.
      Patients received DEX 30 minutes before DNR 45 mg/m2 or MTX 10 mg/m2 in doses
      eight to 13 times higher (DNR) or 30 to 60 times higher (MTX) in the treatment
      cycle with 10 high doses (2,000 mg/m2/12 hr) of cytosine arabinoside plus two
      doses of DNR or MTX on the fourth and fifth day. When this cycle was used as
      reinduction therapy, complete remission was achieved in all five cases. A cycle
      of MTX and etoposide was given three times with DEX as consolidation.
      Myelotoxicity of the treatment cycles with DEX was similar to the cycles without
      it. Two patients received cumulative anthracyclines doses corresponding to more
      than 1,300 and 1,000 mg/m2 of DNR, respectively; the remaining five relapsed
      patients received 550 to 850 mg/m2 of DNR, all without signs of cardiac toxicity.
      Delayed administration of DEX after cumulative doses of DNR 500 mg/m2 in AML
      patients at relapse provides cardioprotection against DNR or MTX in combination
      with high doses of cytosine arabinoside. This type of chemotherapy seems to be
      effective for remission induction in relapsed, heavily pretreated AML patients or
      in patients with impaired heart functions.

PMID- 9768827
TI  - Use of dexrazoxane and other strategies to prevent cardiomyopathy associated with
      doxorubicin-taxane combinations.
AB  - Doxorubicin (DOX) plus paclitaxel is an active combination for patients with
      metastatic breast cancer, producing objective response in approximately 50% to
      90% of patients. The drugs may be combined using different doses and schedules.
      When 60 mg/m2 of DOX is given by intravenous bolus followed 15 to 30 minutes
      later by 200 mg/m2 of paclitaxel (given as a 3-hour infusion), approximately 20%
      of patients will have a substantial decrease in their left ventricular ejection
      fraction below normal after four cycles of therapy (or a cumulative DOX dose of
      240 mg/m2). Approximately 4% will have symptoms of congestive heart failure.
      After eight cycles of therapy, or a cumulative DOX dose of 480 mg/m2,
      approximately 50% of patients will have a decrease in left ventricular ejection
      fraction below normal and 20% of patients will develop clinical evidence of
      congestive heart failure. This is a higher than expected incidence of congestive
      heart failure when compared with retrospectively derived historical data.
      Paclitaxel increases the area under the curve of DOX by approximately 30% when
      given before or after DOX, providing an explanation for this phenomenon. Several
      strategies seem to be associated with a reduced incidence of cardiac toxicity,
      including the use of dexrazoxane with the combination, restricting the cumulative
      DOX dose to < or = 360 mg/m2, increasing the interval between administration of
      the drugs, and use of other taxanes (eg, docetaxel) or other less cardiotoxic
      anthracyclines (eg, epirubicin or liposomal DOX). Most of these strategies were
      evaluated in noncomparative phase I/II trials, and further study will be required
      to determine the role of anthracycline-taxane combinations in the management of
      patients with operable and advanced breast cancer, and to determine a combination
      that has the most favorable therapeutic index.

PMID- 9768828
TI  - Epidemiology of anthracycline cardiotoxicity in children and adults.
AB  - Anthracyclines, potent cytotoxic agents used to treat a broad spectrum of
      malignancies, are limited in their use by an attendant risk of cardiotoxicity.
      Malignancies affect all age ranges, and anthracyclines are used in all age
      ranges, thereby exposing a broad population of patients to the development of
      heart disease. For some treated patients, anthracyclines affect cardiac muscle,
      resulting in cardiomyopathy. The type and degree of cardiomyopathy, as well as
      when during or after treatment the condition occurs, are dependent on what risk
      factors are present. Age is a major risk factor. Children and adults may develop
      restrictive and dilated cardiomyopathy. The length of subsequent survival and
      amount of subsequent somatic growth may influence late anthracycline-associated
      cardiac outcome. Early cardiotoxicity, occurring during or within 1 year of
      completion of treatment, is the largest risk factor for the development of late
      cardiotoxicity, which occurs beyond a year of completion of treatment. Risk
      factors, which appear to be specific for early cardiotoxicity in children,
      include black race, trisomy 21, and the use of amsacrine therapy after
      anthracycline therapy. More cardiotoxic effects are seen in survivors of
      childhood cancer, the longer from completion of treatment a patient is followed.
      Cumulative as well as peak anthracycline doses affect adults and children alike,
      and cardiotoxicity occurs early and late. In adults, left ventricular
      contractility is affected by anthracyclines. Children may manifest impairment of
      left ventricular contractility and increased afterload due to thinning of left
      ventricular walls. Patients with an early presentation of depressed left
      ventricular contractility are likely to show progression of cardiac disease with
      time. In addition, female gender appears to affect early and late cardiotoxicity
      in both adults and children, although this risk factor has been described
      predominantly in the survivors of childhood cancer. Thus, although anthracycline
      chemotherapy has improved overall survivorship of patients with cancer, there is
      a significant risk of cardiotoxicity associated with this class of drugs.

PMID- 9768829
TI  - Ameliorating anthracycline cardiotoxicity in children with cancer: clinical
      trials with dexrazoxane.
AB  - Anthracyclines have major activity against a broad range of childhood cancers.
      Concern over the risk of long-term cardiotoxicity associated with their use has
      called into question the role of these agents in the frontline treatment of many
      patients. Dexrazoxane was developed as a specific cardioprotectant "antidote"
      which can prevent anthracycline cardiotoxicity without inhibiting its antitumor
      effect. To date, four clinical trials of dexrazoxane have been conducted in
      pediatric cancer patients (primarily with sarcomas). The two largest series,
      conducted at the National Cancer Institute Pediatric Branch, demonstrated
      significant short-term cardioprotection with no evidence of interference with
      antitumor activity. Additional clinical trials are ongoing, or planned to open
      shortly, to better evaluate the role of dexrazoxane in the treatment of childhood
      cancer. These studies, being conducted on larger numbers of patients with better
      prospects for cure, are expected to definitviely answer the outstanding questions
      of whether preventing short-term, subclinical cardiotoxicity will translate into
      long-term cardioprotection, and whether the use of dexrazoxane interferes with
      the anti-tumor efficacy of doxorubicin-containing regimens.

PMID- 9768830
TI  - Antineoplastic activity of continuous exposure to dexrazoxane: potential new role
      as a novel topoisomerase II inhibitor.
AB  - Although originally developed as an antitumor agent in the 1970s, dexrazoxane
      (DEX) is currently used as a cardioprotective agent in combination with
      doxorubicin (DOX). Due to concerns about anthracycline-induced cardiotoxicity at
      higher cumulative doses, many investigators have chosen to administer DOX by
      prolonged infusion. Therefore, with the ultimate goal of combining infusional DEX
      and DOX, we performed a phase I study of intravenous DEX alone as a 96-hour
      infusion. Surprisingly, the maximum tolerated dose of DEX identified in this
      study was 10- to 15-fold lower than previously determined using different
      schedules of administration. Results of pharmacokinetic studies in support of the
      trial have found that steady-state DEX plasma concentrations in the range of 4 to
      5 micromol/L can be achieved safely. Because previous experiments have explored
      the ability of DEX to inhibit the catalytic activity topoisomerase II at low
      micromolar concentrations and due to a lack of in vitro cytotoxicity data for
      long-term exposures, we performed further laboratory studies to provide a context
      for our pharmacokinetic findings. As a result of these correlative studies, we
      have found that prolonged exposures to DEX are cytotoxic to human leukemic cells
      at concentrations that are clinically achievable.

PMID- 9768831
TI  - Identifying the missing links: genes that connect neural induction and primary
      neurogenesis in vertebrate embryos.

PMID- 9768832
TI  - Activity and synaptic receptor targeting: the long view.

PMID- 9768833
TI  - Genes for normal behavioral variation: recent clues from flies and worms.

PMID- 9768834
TI  - Neuroscience of addiction.

PMID- 9768835
TI  - Tomosyn binds t-SNARE proteins via a VAMP-like coiled coil.

PMID- 9768836
TI  - A novel signaling pathway from rod photoreceptors to ganglion cells in mammalian
      retina.
AB  - Current understanding suggests that mammalian rod photoreceptors connect only to
      an ON-type bipolar cell. This rod-specific bipolar cell excites the All amacrine
      cell, which makes connections to cone-specific bipolar cells of both ON and OFF
      type; these, in turn, synapse with ganglion cells. Recent work on rabbit retina
      has shown that rod signals can also reach ganglion cells without passing through
      the rod bipolar cell. This route was thought to be provided by electrical gap
      junctions, through which rods signal directly to cones and thence to cone bipolar
      cells. Here, we show that the mouse retina also provides a rod pathway bypassing
      the rod bipolar cell, suggesting that this is a common feature in mammals.
      However, this alternative pathway does not require cone photoreceptors; it is
      perfectly intact in a transgenic mouse whose retina lacks cones. Instead, the
      results can be explained if rods connect directly to OFF bipolar cells.

PMID- 9768837
TI  - Phosphorylation and inhibition of olfactory adenylyl cyclase by CaM kinase II in
      Neurons: a mechanism for attenuation of olfactory signals.
AB  - Acute desensitization of olfactory signaling is a critical property of the
      olfactory system that allows animals to detect and respond to odorants.
      Correspondingly, an important feature of odorant-stimulated cAMP increases is
      their transient nature, a phenomenon that may be attributable to the unique
      regulatory properties of the olfactory adenylyl cyclase (AC3). AC3 is stimulated
      by receptor activation and inhibited by Ca2+ through Ca2+/calmodulin kinase II
      (CaMKII) phosphorylation at Ser-1076. Since odorant-stimulated cAMP increases are
      accompanied by elevated intracellular Ca2+, CaMKII inhibition of AC3 may
      contribute to termination of olfactory signaling. To test this hypothesis, we
      generated a polyclonal antibody specific for AC3 phosphorylated at Ser-1076. A
      brief exposure of mouse olfactory cilia or primary olfactory neurons to odorants
      stimulated phosphorylation of AC3 at Ser-1076. This phosphorylation was blocked
      by inhibitors of CaMKII, which also ablated cAMP decreases associated with
      odorant-stimulated cAMP transients. These data define a novel mechanism for
      termination of olfactory signaling that may be important in olfactory responses.

PMID- 9768838
TI  - Regulation of class I MHC gene expression in the developing and mature CNS by
      neural activity.
AB  - To elucidate molecular mechanisms underlying activity-dependent synaptic
      remodeling in the developing mammalian visual system, we screened for genes whose
      expression in the lateral geniculate nucleus (LGN) is regulated by spontaneously
      generated action potentials present prior to vision. Activity blockade did not
      alter expression in the LGN of 32 known genes. Differential mRNA display,
      however, revealed a decrease in mRNAs encoding class I major histocompatibility
      complex antigens (class I MHC). Postnatally, visually driven activity can
      regulate class I MHC in the LGN during the final remodeling of retinal ganglion
      cell axon terminals. Moreover, in the mature hippocampus, class I MHC mRNA levels
      are increased by kainic acid-induced seizures. Normal expression of class I MHC
      mRNA is correlated with times and regions of synaptic plasticity, and
      immunohistochemistry confirms that class I MHC is present in specific subsets of
      CNS neurons. Finally, beta2-microglobulin, a cosubunit of class I MHC, and
      CD3zeta, a component of a receptor complex for class I MHC, are also expressed by
      CNS neurons. These observations indicate that class I MHC molecules, classically
      thought to mediate cell-cell interactions exclusively in immune function, may
      play a novel role in neuronal signaling and activity-dependent changes in
      synaptic connectivity.

PMID- 9768839
TI  - BDNF has opposite effects on the quantal amplitude of pyramidal neuron and
      interneuron excitatory synapses.
AB  - Recently, we have identified a novel form of synaptic plasticity that acts to
      stabilize neocortical firing rates by scaling the quantal amplitude of AMPA
      mediated synaptic inputs up or down as a function of neuronal activity. Here, we
      show that the effects of activity blockade on quantal amplitude are mediated
      through the neurotrophin brain-derived neurotrophic factor (BDNF). Exogenous BDNF
      prevented, and a TrkB-IgG fusion protein reproduced, the effects of activity
      blockade on pyramidal quantal amplitude. BDNF had opposite effects on pyramidal
      neuron and interneuron quantal amplitudes and modified the ratio of pyramidal
      neuron to interneuron firing rates. These data demonstrate a novel role for BDNF
      in the homeostatic regulation of excitatory synaptic strengths and in the
      maintenance of the balance of cortical excitation and inhibition.

PMID- 9768840
TI  - The cloned capsaicin receptor integrates multiple pain-producing stimuli.
AB  - Capsaicin, the main pungent ingredient in "hot" chili peppers, elicits buming
      pain by activating specific (vanilloid) receptors on sensory nerve endings. The
      cloned vanilloid receptor (VR1) is a cation channel that is also activated by
      noxious heat. Here, analysis of heat-evoked single channel currents in excised
      membrane patches suggests that heat gates VR1 directly. We also show that protons
      decrease the temperature threshold for VR1 activation such that even moderately
      acidic conditions (pH < or = 5.9) activate VR1 at room temperature. VR1 can
      therefore be viewed as a molecular integrator of chemical and physical stimuli
      that elicit pain. Immunocytochemical analysis indicates that the receptor is
      located in a neurochemically heterogeneous population of small diameter primary
      afferent fibers. A role for VR1 in injury-induced hypersensitivity at the level
      of the sensory neuron is presented.

PMID- 9768841
TI  - Cell type and pathway dependence of synaptic AMPA receptor number and variability
      in the hippocampus.
AB  - It has been suggested that some glutamatergic synapses lack functional AMPA
      receptors. We used quantitative immunogold localization to determine the number
      and variability of synaptic AMPA receptors in the rat hippocampus. Three classes
      of synapses show distinct patterns of AMPA receptor content. Mossy fiber synapses
      on CA3 pyramidal spines and synapses on GABAergic interneurons are all
      immunopositive, have less variability, and contain 4 times as many AMPA receptors
      as synapses made by Schaffer collaterals on CA1 pyramidal spines and by
      commissural/ associational (C/A) terminals on CA3 pyramidal spines. Up to 17% of
      synapses in the latter two connections are immunonegative. After calibrating the
      immunosignal (1 gold = 2.3 functional receptors) at mossy synapses of a 17-day
      old rat, we estimate that the AMPA receptor content of C/A synapses on CA3
      pyramidal spines ranges from <3 to 140. A similar range is found in adult
      Schaffer collateral and C/A synapses.

PMID- 9768842
TI  - Activation of AMPA, kainate, and metabotropic receptors at hippocampal mossy
      fiber synapses: role of glutamate diffusion.
AB  - Glutamatergic transmission at mossy fiber (MF) synapses on CA3 pyramidal neurons
      in the hippocampus is mediated by AMPA, kainate, and NMDA receptors and undergoes
      presynaptic modulation by metabotropic glutamate receptors. The recruitment of
      different receptors has thus far been studied by altering presynaptic stimulation
      to modulate glutamate release and interfering pharmacologically with receptors
      and transporters. Here, we introduce two novel experimental manipulations that
      alter the fate of glutamate molecules following release. First, an enzymatic
      glutamate scavenger reduces the postsynaptic response as well as presynaptic
      modulation by metabotropic receptors. At physiological temperature, however, the
      scavenger is effective only when glutamate uptake is blocked, revealing a role of
      active transport in both synaptic and extrasynaptic communication. Second, AMPA
      and kainate receptor-mediated postsynaptic signals are enhanced when
      extracellular diffusion is retarded by adding dextran to the perfusion solution,
      as is feedback modulation by metabotropic receptors, suggesting that the
      receptors are not saturated under baseline conditions. These results show that
      manipulating the spatiotemporal profile of glutamate following exocytosis can
      alter the involvement of different receptors in synaptic transmission.

PMID- 9768843
TI  - Role of the carboxy-terminal region of the GluR epsilon2 subunit in synaptic
      localization of the NMDA receptor channel.
AB  - The synaptic localization of the N-methyl-D-aspartate (NMDA) type glutamate
      receptor (GluR) channel is a prerequisite for synaptic plasticity in the brain.
      We generated mutant mice carrying the carboxy-terminal truncated GluR epsilon2
      subunit of the NMDA receptor channel. The mutant mice died neonatally and failed
      to form barrelette structures in the brainstem. The mutation greatly decreased
      the NMDA receptor-mediated component of hippocampal excitatory postsynaptic
      potentials and punctate immunofluorescent labelings of GluR epsilon2 protein in
      the neuropil regions, while GluR epsilon2 protein expression was comparable.
      Immunostaining of cultured cerebral neurons showed the reduced punctate staining
      of the truncated GluR epsilon2 protein at synapses. These results suggest that
      the carboxy-terminal region of the GluRepsilon2 subunit is important for
      efficient clustering and synaptic localization of the NMDA receptor channel.

PMID- 9768845
TI  - CaMKIIbeta functions as an F-actin targeting module that localizes
      CaMKIIalpha/beta heterooligomers to dendritic spines.
AB  - Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine
      protein kinase that regulates long-term potentiation and other forms of neuronal
      plasticity. Functional differences between the neuronal CaMKIIalpha and
      CaMKIIbeta isoforms are not yet known. Here, we use green fluorescent protein
      tagged (GFP-tagged) CaMKII isoforms and show that CaMKIIbeta is bound to F-actin
      in dendritic spines and cell cortex while CaMKIIalpha is largely a cytosolic
      enzyme. When expressed together, the two isoforms form large heterooligomers, and
      a small fraction of CaMKIIbeta is sufficient to dock the predominant CaMKIIalpha
      to the actin cytoskeleton. Thus, CaMKIIbeta functions as a targeting module that
      localizes a much larger number of CaMKIIalpha isozymes to synaptic and
      cytoskeletal sites of action.

PMID- 9768844
TI  - Novel anchorage of GluR2/3 to the postsynaptic density by the AMPA receptor
      binding protein ABP.
AB  - We report the cloning of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic
      acid (AMPA) receptor-binding protein (ABP), a postsynaptic density (PSD) protein
      related to glutamate receptor-interacting protein (GRIP) with two sets of three
      PDZ domains, which binds the GluR2/3 AMPA receptor subunits. ABP exhibits
      widespread CNS expression and is found at the postsynaptic membrane. We show that
      the protein interactions of the ABP/GRIP family differ from the PSD-95 family,
      which binds N-methyl-D-aspartate (NMDA) receptors. ABP binds to the GluR2/3 C
      terminal VKI-COOH motif via class II hydrophobic PDZ interactions, distinct from
      the class I PSD-95-NMDA receptor interaction. ABP and GRIP also form homo- and
      heteromultimers through PDZ-PDZ interactions but do not bind PSD-95. We suggest
      that the ABP/GRIP and PSD-95 families form distinct scaffolds that anchor,
      respectively, AMPA and NMDA receptors.

PMID- 9768846
TI  - Dissociation between Ca2+-triggered synaptic vesicle exocytosis and clathrin
      mediated endocytosis at a central synapse.
AB  - We have tested whether action potential-evoked Ca2+ influx is required to
      initiate clathrin-mediated synaptic vesicle endocytosis in the lamprey
      reticulospinal synapse. Exo- and endocytosis were temporally separated by a
      procedure involving tonic action potential stimulation and subsequent removal of
      extracellular Ca2+ (Ca2+e). A low concentration of Ca2+ ([Ca2+]e of 11 microM)
      was found to be required for the induction of early stages of endocytosis.
      However, the entire endocytic process, from the formation of clathrin-coated
      membrane invaginations to the generation of synaptic vesicles, proceeded in the
      absence of action potential-mediated Ca2+ entry. Our results indicate that the
      membrane of synaptic vesicles newly incorporated in the plasma membrane is a
      sufficient trigger of clathrin-mediated synaptic vesicle endocytosis.

PMID- 9768847
TI  - The activation gate of a voltage-gated K+ channel can be trapped in the open
      state by an intersubunit metal bridge.
AB  - Voltage-activated K+ channels are integral membrane proteins containing a
      potassium-selective transmembrane pore gated by changes in the membrane
      potential. This activation gating (opening) occurs in milliseconds and involves a
      gate at the cytoplasmic side of the pore. We found that substituting cysteine at
      a particular position in the last transmembrane region (S6) of the homotetrameric
      Shaker K+ channel creates metal binding sites at which Cd2+ ions can bind with
      high affinity. The bound Cd2+ ions form a bridge between the introduced cysteine
      in one channel subunit and a native histidine in another subunit, and the bridge
      traps the gate in the open state. These results suggest that gating involves a
      rearrangement of the intersubunit contacts at the intracellular end of S6. The
      recently solved structure of a bacterial K+ channel shows that the S6 homologs
      cross in a bundle, leaving an aperture at the bundle crossing. In the context of
      this structure, the metal ions form a bridge between a cysteine above the bundle
      crossing and a histidine below the bundle crossing in a neighboring subunit. Our
      results suggest that gating occurs at the bundle crossing, possibly through a
      change in the conformation of the bundle itself.

PMID- 9768848
TI  - Biotinylation of single cysteine mutants of the glutamate transporter GLT-1 from
      rat brain reveals its unusual topology.
AB  - In the central nervous system, (Na+ + K+)-coupled glutamate transporters restrict
      the neurotoxicity of this transmitter and limit the duration of synaptic
      excitation at some synapses. The various isotransporters exhibit a particularly
      high homology in an extended hydrophobic domain of ill-defined topology that
      contains several determinants involved in ion and transmitter binding. Here, we
      describe the determination of the membrane topology of the cloned astroglial
      glutamate transporter GLT-1. A series of functional transporters containing
      single cysteines was engineered. Their topological disposition was determined by
      using a biotinylated sulfhydryl reagent. The glutamate transporter has eight
      transmembrane domains long enough to span the membrane as et heiices. Strikingly,
      between the seventh and eighth domains, a structure reminiscent of a pore loop
      and an outward-facing hydrophobic linker are positioned.

PMID- 9768849
TI  - Polyglutamine-expanded human huntingtin transgenes induce degeneration of
      Drosophila photoreceptor neurons.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder.
      Disease alleles contain a trinucleotide repeat expansion of variable length,
      which encodes polyglutamine tracts near the amino terminus of the HD protein,
      huntingtin. Polyglutamine-expanded huntingtin, but not normal huntingtin, forms
      nuclear inclusions. We describe a Drosophila model for HD. Amino-terminal
      fragments of human huntingtin containing tracts of 2, 75, and 120 glutamine
      residues were expressed in photoreceptor neurons in the compound eye. As in human
      neurons, polyglutamine-expanded huntingtin induced neuronal degeneration. The age
      of onset and severity of neuronal degeneration correlated with repeat length, and
      nuclear localization of huntingtin presaged neuronal degeneration. In contrast to
      other cell death paradigms in Drosophila, coexpression of the viral antiapoptotic
      protein, P35, did not rescue the cell death phenotype induced by polyglutamine
      expanded huntingtin.

PMID- 9768850
TI  - In situ detection of chromosome bridge formation and delayed reproductive death
      in normal human embryonic cells surviving X irradiation.
AB  - We investigated delayed reproductive death and chromosome bridge formation in
      mitotic cells in colonies of normal human embryonic cells which survived exposure
      to 6 Gy of X rays. Eighteen primary clones each derived from control and
      irradiated cultures were isolated and secondary colonies were grown up. Six of
      the primary clones surviving the irradiation showed significantly lower cloning
      efficiencies than the control clones (P < 0.001), while the rest of the surviving
      clones showed a cloning efficiency similar to those of the control clones. The
      average cloning efficiency of control and surviving clones was 16.4 and 7.2%,
      respectively. Reduced cloning efficiencies were also observed in the tertiary
      colony formation, indicating that the persistent decrease in cloning efficiency
      was inherited over 40 generations after X irradiation in normal human cells. Five
      of nine primary clones surviving the irradiation also frequently contained
      multiple giant cells in the colonies, while this was a rare event in the progeny
      of control clones. Furthermore, we analyzed in situ chromosome segregation in
      anaphase cells appearing during the formation of the secondary colonies. A
      significantly higher frequency of chromosome bridge formation was found in four
      of the surviving clones which received 6 Gy (P < 0.001), and the frequency of
      micronuclei was also increased in the surviving clones. These results provide
      evidence that genetic instability is induced in normal human embryonic cells by
      low-LET radiation, and that misrejoining of the broken chromosome ends is
      increased in the progeny of cells surviving X irradiation.

PMID- 9768851
TI  - The nucleus is the target for radiation-induced chromosomal instability.
AB  - We have previously described chromosomal instability in cells of a human-hamster
      hybrid cell line after exposure to X rays. Chromosomal instability in these cells
      is characterized by the appearance of novel chromosomal rearrangements multiple
      generations after exposure to ionizing radiation. To identify the cellular
      target(s) for radiation-induced chromosomal instability, cells were treated with
      125I-labeled compounds and frozen. Radioactive decays from 125I cause damage to
      the cell primarily at the site of their decay, and freezing the cells allows
      damage to accumulate in the absence of other cellular processes. We found that
      the decay of 125I-iododeoxyuridine, which is incorporated into the DNA, caused
      chromosomal instability. While cell killing and first-division chromosomal
      rearrangements increased with increasing numbers of 125I decays, the frequency of
      chromosomal instability was independent of dose. Chromosomal instability could
      also be induced from incorporation of 125I-iododeoxyuridine without freezing the
      cells for accumulation of decays. This indicates that DNA double-strand breaks in
      frozen cells resulting from 125I decays failed to lead to instability.
      Incorporation of an 125I-labeled protein (125I-succinyl-concanavalin A), which
      was internalized into the cell and/or bound to the plasma membrane, neither
      caused chromosomal instability nor potentiated chromosomal instability induced by
      125I-iododeoxyuridine. These results show that the target for radiation-induced
      chromosomal instability in these cells is the nucleus.

PMID- 9768852
TI  - Radioprotection against lethal damage caused by chronic irradiation with
      radionuclides in vitro.
AB  - To examine the capacity of chemical protectors to mitigate damage caused by
      chronic irradiation by incorporated radionuclides in vitro, cells must be
      maintained in the presence of the protector during the course of the irradiation.
      Such long exposures to chemical protectors at concentrations high enough to
      afford protection usually results in extreme chemotoxicity. To overcome this
      problem, experimental conditions were developed to allow Chinese hamster V79
      cells to be maintained in 5% DMSO for prolonged periods (up to 72 h) with no
      observable chemotoxicity. Under these conditions, the capacity of DMSO to protect
      against damage to V79 cells caused by unbound 32P and 3H2O and DNA-incorporated
      (131)IdU, [3H]dThd and 125IdU was examined. The dose modification factors for
      32P, 3H2O, (131)IdU, [3H]dThd and 125IdU were 2.6+/-0.5, 2.3+/-0.3, 1.0+/-0.1,
      1.16+/-0.07 and 1.07+/-0.02, respectively. These results show that 5% DMSO is
      capable of protecting cultured V79 cells against lethal damage caused by beta
      particles emitted by unbound 32P and 3H2O, whereas little or no protection is
      afforded against damage caused by beta particles emitted by DNA-incorporated
      (131)I and 3H or low-energy Auger electrons emitted by DNA-incorporated 125I.

PMID- 9768853
TI  - Biological dosimetry of beta-ray exposure from tritium using chromosome
      translocations in human lymphocytes analyzed by fluorescence in situ
      hybridization.
AB  - Radiation exposures from tritium make up a substantial fraction of the
      occupational and accidental radiation exposures associated with the nuclear power
      industry. Tritiated water, the most abundant form of tritium, is of particular
      interest because it is readily taken up by human cells and its irradiation of the
      cells is spread over a period of days. To approximate the prolonged exposure and
      the conditions that the cells of an individual would experience in vivo, we
      irradiated human lymphocytes with tritiated water for 48 h in a 1:1 blood:medium
      mix. For estimation of the tritium beta-ray dose, a cellular water content of
      0.78, based on measurements of human lymphoblastoid cells in culture medium, was
      used. A modified dose calculation formula was developed for the radiation
      exposure conditions. A total of 48,014 metaphases (14,482 in irradiated samples
      and 33,532 in control, unirradiated samples) in human lymphocytes cultured for 72
      h after exposure were analyzed for chromosome translocations using fluorescence
      in situ hybridization. The linear slope (alpha coefficient) of the dose-response
      curve was measured to be (3.93+/-0.42) x 10(-2) and (5.26+/-0.48) x 10(-2)
      translocations per cell per gray for complete translocations (tc) and complete
      translocations plus incomplete translocations [ti(Ab)], respectively, when the
      data were fitted to a linear model using a weighted least-squares method. The
      alpha coefficient for tc is significantly lower than that for conventionally
      measured dicentrics after tritium beta irradiation, but the alpha coefficient for
      tc + ti(Ab) does not differ significantly from that for dicentrics. This is in
      agreement with theoretical considerations. The importance of scoring criteria is
      stressed. The frequency of tc + ti(Ab) is proposed to be a reliable biodosimeter
      for tritium exposures, and its practical use in a dose reconstruction is
      presented.

PMID- 9768854
TI  - Radiation fields backscattered from material interfaces: I. Biological
      effectiveness.
AB  - Confluent cultures of CHO-K1 and CHO-xrs5 cells were irradiated attached to 6
      microm Mylar with 137Cs gamma rays and 200 kVp X rays adjacent to scattering
      materials consisting of polystyrene, glass, aluminum, copper, tin and lead. The
      absorbed dose in cell nuclei was estimated from measurements of backscattered
      dose made with a parallel-plate ion chamber with a 5-microm Mylar window and a
      gas volume whose thickness was equivalent to approximately 2.6 microm of cells or
      tissue. Cell inactivation after various doses was measured by clonogenic assays
      after trypsinization and enumeration. Survival curves constructed from data
      pooled from at least two independent experiments were best fitted to a linear
      quadratic (LQ) or a linear equation for CHO-K1 and CHO-xrs5 cells, respectively.
      An average distance of 9.3+/-1.9 microm from the scattering surfaces to the
      midline of nuclei for both the cell lines was estimated from electron micrographs
      of fixed cell sections. The major differences in biological effect observed when
      the cells were irradiated adjacent to these materials could be largely explained
      by the differences in the physical dose. Further analyses using the LQ equation
      suggested additional biological effects with implications for the mechanisms
      involved. CHO-K1 cells showed a small but consistent increase in the low-dose
      (alpha-inactivation coefficient) mechanism for both radiations scattered from
      high-Z material. An increased value of the alpha coefficient suggests an increase
      in RBE which could be associated with a higher proportion of low-energy and track
      end electrons in these fields. The radiation fields which produced maximum single
      hit killing in CHO-K1 cells also produced less killing by the quadratic (beta
      inactivation coefficient) mechanism. In contrast, when similarly irradiated, CHO
      xrs5 cells exhibited significantly lower alpha coefficients of inactivation. The
      mechanistic basis for this opposite effect of backscattered radiations in these
      cell lines is as yet unknown.

PMID- 9768855
TI  - Recovery from sublethal damage is reversibly inhibited by hypertonic saline: the
      effects of 0.23 M sodium chloride.
AB  - We previously showed that 0.23 M NaCl was able to fix slowly repairing
      potentially lethal damage (PLD), and that this slowly repairing PLD is distinct
      from rapidly repairing PLD that is sensitive to 0.5 M NaCl (Ikebuchi et al.,
      Radiat. Res. 141, 19-27, 1995). In the present study, the effect of 0.23 M NaCl
      on repair of sublethal damage (SLD) was examined in cells of three rodent cell
      lines with normal radiosensitivity (Chinese hamster V79, BALB/c 3T3, RD13B2) and
      two radiosensitive lines derived from severe combined immunodeficient (scid)
      mice. Repair of SLD was detected as an increase in survival when the radiation
      dose was fractionated with an interval of incubation between the two doses.
      Repair of SLD occurred in V79 and BALB/c 3T3 cells but did not occur in the two
      scid cell lines which were defective in repair of double-strand breaks (DSBs),
      demonstrating that repair of DSBs is involved in repair of SLD. This was
      confirmed by the observation that repair of SLD occurred in RD13B2 cells, the
      scid line which had regained the ability to repair DSBs. When the V79 and BALB/c
      3T3 cells were treated with 0.23 M NaCl during the interval between the split
      doses, repair of SLD was completely inhibited. On the other hand, repair of SLD
      occurred when the cells were incubated in culture medium between the treatment
      with 0.23 M NaCl and the second dose. From these observations, it is concluded
      that the inhibition of repair of SLD by 0.23 M NaCl is reversible, which is in
      contrast to the irreversible inhibition of repair of PLD by 0.23 M NaCl found
      previously. In addition, the fact that scid cells that were shown to have the
      ability to repair PLD that is sensitive to 0.23 M NaCl had little capacity to
      repair SLD suggests that there may be different processes involved in the two
      types of cellular repair.

PMID- 9768856
TI  - Differential sensitivity of three sublines of the rat Dunning prostate tumor
      system R3327 to radiation and/or local tumor hyperthermia.
AB  - To better understand the relationship of the growth characteristics of tumor
      tissues and their response to ionizing radiation alone and in combination with
      local tumor hyperthermia, we compared three different tumor sublines of the
      Dunning rat prostate carcinoma R3327. This report includes results obtained with
      the anaplastic AT1 subline (volume doubling time 5.2 days), the moderately
      differentiated mucin-secreting HI subline (volume doubling time about 9 days) and
      the well-differentiated, hormone-dependent H subline (volume doubling time about
      17 days). The effects of single doses of photons (10 to 40 Gy) with and without
      local tumor hyperthermia (35 min immersion at 43.5 degrees C) were quantified by
      growth delay. The time to reach five times the volume at the time of treatment
      after 30 Gy alone was found to be 56.0, 134.9 and 184.0 days for the R3327-AT1,
      HI and H tumors, respectively. The R3327-H tumor was more radiosensitive than the
      AT1 or HI subline. Five of nine R3327-H tumors were controlled locally with a
      single dose of photons (40 Gy). Local tumor hyperthermia alone induced growth
      delay in both differentiated tumors, while the anaplastic tumor subline did not
      respond. Combined treatment modalities with heat applied directly after
      irradiation revealed isoeffective thermal enhancement ratios for 30 Gy which
      decreased from 1.59 for the AT1 tumor and 1.42 for the HI tumor to 1.23 in the
      well-differentiated subline R3327-H.

PMID- 9768857
TI  - Moderate doses of intraoperative radiation severely suppress early strength of
      anastomoses in the rat colon.
AB  - Intraoperative irradiation appears to be a valuable addition to the modalities
      available to treat patients with large bowel cancer. However, its potential
      effect on healing of anastomoses has not been investigated extensively. For this
      purpose, male Wistar rats underwent colonic resection. Subsequently, 1 cm of each
      bowel end was irradiated with doses of 10, 15, 20 or 25 Gy and intestinal
      continuity was restored. After 3 or 7 days, animals were killed and the
      anastomoses were analyzed for bursting pressure (intraluminal force), breaking
      strength (longitudinal force) and hydroxyproline content. Intraoperative
      irradiation led to a massive (40-70%) and significant (P < 0.025) reduction in
      bursting pressure 3 days after operation compared to the control group for every
      dose used. After 7 days, the bursting site was outside the area of the
      anastomosis in all groups. The breaking strength at day 3 was also reduced, even
      after 10 Gy. At day 7, when tearing still occurred in the wound area, the
      breaking strength was still significantly lower in the 15- and 25-Gy groups than
      in the control group. The hydroxyproline content of the anastomoses was
      significantly reduced only after irradiation with the higher doses. Thus
      intraoperative irradiation constitutes a threat to early strength of anastomoses
      in the rat colon, and even at moderate doses it may threaten the integrity of the
      anastomosis.

PMID- 9768858
TI  - Effects of volume irradiated on the function of the canine ureter.
AB  - This study was designed to investigate the influence of the volume irradiated on
      the probability of ureteral complications and to provide data for volume
      modeling. One hundred thirty-four purpose-bred beagle dogs received single
      intraoperative doses of 6 MeV electrons ranging from 12 to 54 Gy to three lengths
      of ureter: 2, 4 or 8 cm. The response was evaluated by excretory urography. The
      ED50 was 21.9 Gy (95% CI 13.3-30 Gy) for 8 cm 3 years after treatment. The
      estimated ED50's were greater than 43 Gy for 4 cm and 85 Gy for 2 cm. Reducing
      the length of ureter irradiated from 8 cm to 4 cm increased the ED50 for ureteral
      dilation by at least a factor of 2, while reduction from 8 cm to 2 cm increased
      the ED50 by at least a factor of 4. The ED50 for renal injury secondary to
      stenosis was 30.5 Gy (95% CI 17.2-232 Gy) when an 8-cm field was irradiated.
      There was a significant effect of volume irradiated on the frequency of ureteral
      stenosis. Reducing the length of ureter included in the treatment field should
      allow delivery of higher doses to tumors without increased complications.

PMID- 9768859
TI  - Induction of mammary tumors in rats by single-dose gamma irradiation at different
      ages.
AB  - The effect of age at exposure on induction of mammary tumors was studied in
      female rats of the inbred WAG/Rij strain. Groups of 40 animals were exposed to a
      single total-body dose of 1 or 2 Gy of 137Cs gamma radiation at ages of 8, 12,
      16, 22, 36 or 64 weeks and were observed for life. Mammary tumors, identified as
      nodules persisting and growing for 6 weeks, were resected and classified
      histologically as carcinoma or fibroadenoma. The age-specific incidence of
      mammary carcinoma was compared with that in a group of 120 unirradiated control
      rats, using lifetime statistical analysis with both parametric and nonparametric
      methods. The excess normalized risk of carcinoma was 0.9 for 1 Gy and 2.2 for 2
      Gy in age groups 8-36 weeks, with no significant differences between the age
      groups. However, irradiation at 64 weeks yielded fewer carcinomas than in the
      controls, the excess normalized risk being -0.7 and -0.3 for 1 and 2 Gy,
      respectively. The occurrence of one or more fibroadenomas did not influence the
      incidence of carcinoma. The present data agree closely with the results reported
      previously for rats irradiated at age 8 or 17 weeks with a dose of 1.2 Gy. The
      reduced risk of radiation exposure at midlife is consistent with the available
      epidemiological data for exposed women. Although our findings have been obtained
      with a single total-body dose that is several orders of magnitude higher than the
      multiple doses delivered to the mammary gland during mammography, it is suggested
      that radiological screening for mammary cancer after the age of menopause will
      not increase the normal incidence of breast cancer.

PMID- 9768860
TI  - The influence of estrogen treatment on induction of mammary carcinoma in rats by
      single-dose gamma irradiation at different ages.
AB  - The effect of age at exposure on induction of mammary carcinoma was studied in
      female rats of the inbred WAG/Rij strain that were treated with estrogen. Groups
      of 40 animals were exposed to a single total-body dose of 1 or 2 Gy of 137Cs
      gamma radiation at age 8, 10, 12, 15, 22, 36 or 64 weeks. Hormone levels in the
      animals were increased by implantation of a pellet containing Estradiol-17beta 2
      weeks prior to irradiation. Animals were killed when moribund. All mammary tumors
      were resected and classified histologically as carcinoma or fibroadenoma. The age
      specific incidence of mammary carcinoma was compared with that in control groups
      of unirradiated estrogen-treated rats using lifetime statistical analysis with
      both parametric and nonparametric methods. The excess normalized risk of
      carcinoma was 7.7 for both 1 and 2 Gy in the age groups 8-15 weeks, with no
      significant differences between the age groups. However, in the age groups 22-64
      weeks, the excess normalized risk decreased with increasing age at exposure.
      Irradiation at 64 weeks yielded fewer carcinomas than in the controls, with an
      excess normalized risk of -0.6 for both 1 and 2 Gy. The excess normalized risk
      was 10-80 in estrogen-treated controls compared to untreated rats. The present
      data agree with the results reported previously for estrogen-treated rats
      irradiated at ages 8 or 17 weeks with doses of 0.3 or 1.2 Gy. The reduced risk of
      radiation exposure at midlife observed in this study in hormone-treated rats has
      also been reported for animals not treated with estrogens. The present findings
      support the earlier conclusion that radiological screening for mammary cancer
      after the age of menopause will not increase the normal incidence of breast
      cancer. Estrogen treatment at midlife may increase the risk of breast cancer in
      women using replacement estrogens during and after menopause.

PMID- 9768861
TI  - Chromosome aberrations in radiation workers with internal deposits of plutonium.
AB  - Chromosome analysis of G-banded peripheral blood lymphocytes was performed on two
      groups of plutonium workers with 20-50% and >50% maximum permissible body burdens
      (MPBB) of plutonium from the British Nuclear Fuels plc (BNFL) facility at
      Sellafield, UK, 10 years after an earlier study had reported increases in both
      symmetrical and asymmetrical aberrations. For each plutonium exposure group there
      was a significant difference in frequencies of symmetrical aberrations between
      plutonium workers, workers with similar histories of exposure to mainly external
      gamma radiation but with little or no intakes of plutonium, and controls with
      negligible exposure (<50 mSv). In contrast, no significant differences for
      asymmetrical aberrations were found, and since these are short-lived, this
      suggests that recent exposure of mature lymphocytes was minimal. Frequencies of
      symmetrical aberrations had increased significantly since the earlier sampling
      time. Additional external radiation exposure was negligible in the plutonium
      worker groups over this period. These results are consistent with the hypothesis
      that hemopoietic precursor cells are being irradiated by internally deposited
      plutonium with subsequent selection resulting in only cells with symmetrical
      aberrations reaching the peripheral lymphocyte pool. After removal of aberrations
      involving only chromosomes 7 and/or 14, which are thought to arise in vivo during
      immunological development, the breakpoints involved in the aberrations were
      distributed randomly among the chromosomes according to length in all three
      groups of workers. Within the chromosomes the distribution between terminal,
      interstitial and centromeric regions for the plutonium workers did not conform to
      that expected, there being an excess in the terminal regions and a deficit in the
      interstitial regions.

PMID- 9768862
TI  - The effect of high-linear energy transfer ions on the electron paramagnetic
      resonance signal induced in alanine.
AB  - Microcrystalline samples of L-alanine irradiated with energetic high-LET cobalt
      and iron ions had different EPR spectra compared to alanine samples irradiated
      with low-LET photons. The differences in the shapes of the EPR spectra and their
      dependence on the microwave power are related to the differences in the microwave
      power saturation of the radicals induced by the various types of ionizing
      radiation. The changes in the shape of the EPR spectra, which were caused by
      increasing microwave power, were more pronounced in samples irradiated with low
      LET radiation than with high-LET particles. This effect showed a long-term
      stability and can be used to monitor radiation quality.

PMID- 9768863
TI  - Autoxidation of ferrous ion complexes: a method for the generation of hydroxyl
      radicals.
AB  - The kinetics of the production of hydroxyl radicals during the autoxidation of
      ferrous ion complexes at pH 7.4 was investigated using the fluorescent probe
      coumarin-3-carboxylic acid. Polyphosphates (tri- and tetrapolyphosphate and their
      adenosine derivatives), citrate, and acetic derivatives of ethyleneamine
      ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid
      (DTPA), triethylenetetraminehexaacetic acid (TTHA), ethylenediamine-(N,N')
      diacetic acid (EDDA) and nitrilotriacetic acid (NTA) were used as iron chelators.
      Production of hydroxyl radical in these chemical systems was compared with that
      by radiation to determine the equivalent doses of radiation that produced equal
      amounts of .OH. The amount of .OH formed during ferrous ion autoxidation is
      determined by the concentration of the complex, its structure and the radical
      scavenging by the chelator molecule. Production of .OH for homologous
      ethylenamine acetates increases with increased complex stability: NTA < EDDA <
      TTHA < EDTA < DTPA. The radiation dose equivalence for 0.1 mM complexes increased
      from 5 Gy for NTA to 25 Gy for DTPA. The radiation dose equivalence for
      polyphosphates was 15 Gy for tripolyphosphate and 32 Gy for tetrapolyphosphate.
      The dose equivalences for adenosine phosphates are lower, 5 Gy for ATP and 10 Gy
      for adenosine tetraphosphate, due to intramolecular .OH scavenging. The rate of
      generation of .OH shows an inverse correlation with the charge of the ferrous ion
      complex, varying from 2 cGy/s for DTPA to 1.2 Gy/s for EDTA. The data presented
      indicate the usefulness of autoxidation of ferrous ion complexes for generation
      of .OH in chemical systems. The ability to control the amount and the rate of
      production of .OH may prove useful for examining the cytotoxic effects of .OH
      generated in biological systems.

PMID- 9768864
TI  - Effectiveness of protons and argon ions in initiating lipid peroxidation in low
      density lipoproteins.
AB  - In this study, human low-density lipoprotein (LDL) vesicles were irradiated with
      73 MeV protons (LET of 1 keV/microm) and 11.4 MeV/nucleon argon ions (LET of 1.52
      MeV/pm) and the effectiveness of charged particles in initiating peroxidation of
      LDLs was investigated. The LDL suspension (6 g/l) was exposed to protons and to
      argon ions in a dose range of 24 Gy to 2.4 kGy. Irradiations were carried out at
      the synchrocyclotron at the CPO and at the UNILAC of the GSI. After irradiation
      three chemical assays were used to study the progression of peroxidation of LDLs:
      the formation of conjugated dienes, the formation of thiobarbituric acid-reactive
      substances (TBARS) and the increase in the relative electrophoretic mobility of
      the LDLs. The results were compared with those obtained after gamma irradiation.
      For protons the yields of the peroxidation products were 10 times lower than
      after gamma irradiation. However, for doses below 200 Gy, protons appeared to be
      more effective than gamma rays in damaging the protein moiety, as deduced from
      the observed increase in the relative electrophoretic mobility of the LDLs. The
      irradiation with argon ions led to a negligible formation of peroxidation
      products, but an increase in the relative electrophoretic mobility of the LDLs
      was observed. The results are indicative of a lower yield of lipid peroxidation
      after irradiation with high-LET particles. In contrast, protons and argon ions
      appear to be more effective in inducing bulk protein and phospholipid damage than
      gamma rays.

PMID- 9768865
TI  - Effects of gamma rays on the stability and size of DNA.
AB  - The effects of gamma radiation on the stability and size of mammalian DNA were
      studied by using thermal transition spectrophotometry and pulsed-field and
      standard agarose gel electrophoresis. The experiments were performed using
      deproteinized calf thymus DNA in buffered deaerated aqueous solutions. A dual
      dose response was observed: a tendency for increased helix stability at "low"
      doses (0-4 Gy) accompanied by a high tendency of the DNA molecules to interact,
      forming larger molecules, followed by a gradual increase of degradation and helix
      instability at higher doses. The results reported here for the low-dose region
      are consistent with the hypothesis of inter- and intramolecular interactions of
      covalent character (crosslinking) in irradiated DNA molecules.

PMID- 9768866
TI  - F values as cytogenetic fingerprints of prior exposure to different radiation
      qualities: prediction, reality and future.

PMID- 9768867
TI  - GABA function in mood disorders: an update and critical review.
AB  - Over the past twenty years, several lines of evidence from preclinical and
      clinical studies has accumulated suggesting that a GABA deficit may be involved
      in mood disorders, particularly in depression, and that increasing GABAergic
      neurotransmission may exert an antidepressant effect and perhaps a mood
      stabilizing effect. Given that GABA has an inhibitory effect on biogenic amine
      neurotransmitters such as norepinephrine and serotonin and this inhibition may be
      involved in local circuits and interneurons, it has been suggested that the
      hypothesis of a GABA deficit in mood disorders does not compete with but
      complements the well-established hypotheses of alterations in noradrenergic and
      serotonergic function in mood disorders. In this paper, we systematically
      reviewed the results from preclinical and clinical studies of GABA function in
      the pathophysiology of mood disorders and in the mechanism of action of mood
      stabilizers, antidepressants and electroconvulsive therapy. We also discussed the
      unifying theory of the neurochemistry of mood disorders, which integrates the
      GABA hypothesis into the biogenic amine hypotheses, and indicated future
      directions for research.

PMID- 9768868
TI  - Variations and interrelation between vasopressin and plasma osmolality in
      diabetic rats with insulin treatment.
AB  - Although it is well known that plasma osmolality and plasma vasopressin (VP)
      levels in diabetes mellitus are higher than in non-diabetic conditions (and that
      these levels return to normality with insulin therapy), there are no existing
      studies which examine for insulin-dependent diabetes, either the persistence of
      daily rhythmic variations of VP or the relationship between this variation and
      daily osmotic oscillations. We have therefore examined nycthaemeral variations in
      both plasma osmolality and plasma VP in normal (C), uncontrolled (D) and
      controlled insulin-dependent streptozotocin diabetic rats (DI). The uncontrolled
      streptozotocin treated rats presented, a loss of VP rhythmicity, together with
      higher values of VP than in both normal and controlled diabetic rats. The VP
      rhythm, however, could be restored with insulin treatment. Furthermore, the
      temporal VP/osmolality ratio in uncontrolled diabetic rats is higher than in
      normal rats, although this ratio does not show the daily rhythmic pattern that is
      present in both normal and diabetic rats treated with insulin. This may indicate
      that the lack of rhythmicity in osmotic regulation is responsible for the absence
      of a circadian rhythm in VP. As a result, we conclude that in uncontrolled
      diabetic rats, the higher VP levels and the loss of VP circadian rhythmicity
      could be due to a higher sensitivity in the osmoregulatory system, together with
      an absence of circadian variation of this system. This circadian variation could
      be responsible for the plasma VP rhythmicity in both normal and controlled
      diabetic rats.

PMID- 9768869
TI  - Mechanisms of action of endothelin-1 in rat adrenal.
AB  - Displacement curves of 125I-Endothelim-1 (ET-1) binding to rat adrenal cells with
      unlabeled ET-1, and the ET-1 receptor-related peptides sarafotoxin and BQ-123,
      show that rat adrenal cortex possess, as its bovine counterpart, two different
      receptors to ET-1 named ET-A and ET-B. Binding of ET-1 to its rat adrenal
      receptors stimulates i) aldosterone production, in vivo and in vitro ii) calcium
      influx, which is mediated through voltage dependent- and receptor operated-
      calcium channels, iii) cholesterol uptake, iv) stimulation of Na+/K+-ATPase and
      iv) diacylglycerol production. While the last effect is mediated through ET-A
      receptors the others involve binding of ET-1 to ET-B receptors. Finally, ouabain
      potentiates the ET-1-mediated stimulation of aldosterone production, suggesting
      that the effect of the peptidic hormone on Na+/K+-ATPase could act as a negative
      feedback mechanism.

PMID- 9768870
TI  - Isotonic ethanol inhibits the generation of superoxide anion in neutrophils by
      inducing cell expansion.
AB  - The effects of ethanol on the production of oxygen-derived free radicals by
      neutrophils are controversial. Osmolarity-mediated alteration of cell volume
      appears to be an important mechanism for regulating neutrophil activity. We
      investigated in neutrophils from healthy volunteers the effect of
      isotonic/hypertonic ethanol on both chemiluminescence amplified by a Cypridina
      luciferin analog in response to N-formyl-Met-Lue-Phe and cell volume measured
      with a Coulter counter. Both isotonic and hypertonic ethanol significantly
      decreased chemiluminescence in a dose-dependent manner. Isotonic ethanol produced
      a greater magnitude of inhibition than hypertonic ethanol (P<0.01). Another
      permeable molecule, urea, and hypotonic solution had the same effects on
      chemiluminescence. Isotonic and hypertonic ethanol caused a prompt cell expansion
      and shrinking, respectively. On the other hand, isotonic sucrose, an impermeable
      molecule, was ineffective in both chemiluminescence and cell volume changes.
      These data suggest that isotonic ethanol inhibits the superoxide anion production
      by inducing cell expansion probably due to increased intracellular osmotic
      pressure caused by rapid ethanol permeation through the plasmalemma. This
      impaired neutrophil function may, in some part, contribute to the susceptibility
      to infection in alcoholics.

PMID- 9768871
TI  - Characterization of nuclear protein binding (AP-1, GR, and STAT) in the
      genetically obese (fa/fa) Zucker rat.
AB  - There is evidence to suggest that obese populations have an increased
      susceptibility to various pathologic disorders. Both AP-1 and STAT nuclear
      binding proteins have been suggested to play a role in certain obesity-related
      diseases. The objective of our studies reported herein was to compare
      constitutive binding activity of nuclear proteins (AP-1, GR, and STAT), that may
      be relevant to obesity-related diseases in the obese (fa/fa) Zucker rat to lean
      (Fa/?) littermates. AP-1, GR, and STAT liver nuclear protein binding activity was
      analyzed using the electrophoretic mobility shift assay (EMSA). EMSA analysis of
      liver nuclear protein from obese and lean Zucker rats revealed high constitutive
      AP-1 binding activity in the obese animals. AP-1 binding activity in the obese
      rats was not further elevated by treatment with phenobarbital, a known inducer of
      AP-1 binding activity. No differences were observed in GR binding to a consensus
      GRE between obese and lean animals; however, STAT binding activity to a consensus
      GAS element was lower in liver tissue from obese Zucker rats. Our findings
      presented herein suggest that the fa/fa Zucker rat may be a suitable obese rodent
      model for studying the roles AP-1 and STAT may play in the pathologies of these
      diseases.

PMID- 9768872
TI  - Acute leptin action on insulin blood level and liver insulin receptor in the rat.
AB  - Aim of the study was to investigate acute leptin effect on insulin blood level
      and liver insulin binding in the rat. The administration of leptin induced time
      and dose dependent decrease in the insulin level, which was statistically
      significant in comparison to the control animals 120 min after administration of
      higher dose of peptide (0.30 +/- 0.05 vs 0.14 +/- 0.01 nmol/l, respectively).
      Simultaneously, we have shown the attenuation of liver sensitivity to insulin 2
      hours after higher leptin dose injection. This phenomenon was caused by the
      decrease of binding capacity of high affinity insulin receptor sites (HAIR),
      which was statistically significant after higher leptin dose administration at
      both time points (0.54 +/- 0.13 vs 0.26 +/- 0.03 and 0.71 +/- 0.12 vs 0.40 +/-
      0.05 pmol/mg protein for 1 and 2 h, respectively). The present study provides
      evidence that leptin, in addition to its inhibitory effect on insulin secretion,
      acts as a modulator of insulin receptor, through the decrease of binding
      capacity. It seems legitimate to suggest that leptin-induced decrease of insulin
      receptor binding capacity may be one of several causes of insulin resistance.

PMID- 9768873
TI  - HLA DR and AB surface antigens correlate with cell shape (surface area).
AB  - In order to help explain some of the various phenomena associated with both
      benign and malignant cells, this study was undertaken to determine if changes in
      the shape of the cell could alter the recognition of the cell. Non-transformed
      Human cells, HEL 299, were evaluated for their shape and surface antigens. A
      direct statistical correlation was found between the two surface antigens HLA AB
      and DR and the cell shape (surface area). The possible significance of this
      phenomena in non transformed human cells to neoplastic proliferation is
      suggested.

PMID- 9768874
TI  - Depression of the hepatic cytochrome P450 by an acute inflammatory reaction:
      characterization of the nature of mediators in human and rabbit serum, and in the
      liver.
AB  - There is increasing evidence suggesting that several mediators are involved in
      the cascade of events leading to the depression of the cytochrome P450 (P450) by
      an inflammatory reaction. The present study aimed to confirm the presence of
      mediators in the serum (RS(INFLA)) and hepatocytes (H(INFLA)) of rabbits with an
      acute inflammatory reaction, and in the serum of humans with an acute upper
      respiratory tract viral infection (HS(URTVI)). The inflammatory reaction was
      induced by the s.c. injection of 5 ml of turpentine. Incubation of RS(INFLA) or
      HS(URTVI) with H(INFLA) depressed the P450, diminished the formation of
      theophylline metabolites (3-methylxanthine, 1-methyluric acid, and 1,3
      dimethyluric acid), and increased lipid peroxidation. The addition of preheated
      RS(INFLA) or HS(URTVI) to H(INFLA) did not diminish the amount of P450 or
      theophylline metabolites, and prevented the increase in lipid peroxidation.
      Incubating the filtrate of RS(INFLA) or HS(URTVI) dialyzed through membranes with
      cut-off of 10, 30, 50 and 100 kd, with H(INFLA) showed that rabbit and human
      mediators have molecular weights ranging from 10 to 30 kd. Incubation of H(INFLA)
      with hepatocytes from control rabbits (H(CONT)) did not decrease further the
      P450. However, when RS(INFLA) was added to co-cultured H(CONT) + H(INFLA), the
      depression of P450 was 37% greater (p<0.05), and the amount of theophylline
      metabolites generated was around 30% (p<0.05) smaller than that observed when
      H(CONT) or H(INFLA) were incubated with RS(INFLA). Based on the present results
      we may speculate that human and rabbit serum mediators are proteins of molecular
      weights ranging from 10 to 30 kd, and in addition, primed hepatocytes once
      exposed to the serum mediators release mediators able to depress the P450 in
      H(CONT).

PMID- 9768875
TI  - Evidence of H3 receptor inhibition by iodoaminopotentidine in the guinea pig
      ileum.
AB  - Activation of histamine H3 receptors by histamine (0.1 to 10 microM), (R)alpha
      methylhistamine and N(alpha)-methylhistamine (0.01 to 0.3 microM) was shown to
      inhibit cholinergic nerve transmission in the guinea-pig ileum.
      Iodoaminopotentidine (IAP 300 nM), a potent H2 receptor antagonist, was found to
      decrease this effect but had no significant effect (P>0.05) on contractile
      responses produced by exogenous acetylcholine (0.2 microM). Dimaprit (0.1 to 10
      microM) an H2 receptor agonist/H3 receptor antagonist, produced no significant
      effect (P>0.05) on the response to cholinergic nerve stimulation but reduced the
      effect of N(alpha)-methylhistamine. Furthermore, ranitidine (10 microM) an H2
      receptor antagonist did not modify the inhibitory effect of histamine. These
      results suggest that IAP may inhibit H3 receptors in the ileum at similar
      concentrations reported to inhibit H2 receptors in functional studies.

PMID- 9768876
TI  - Slide-binding characterization and autoradiographic localization of delta opioid
      receptors in rat and mouse brains with the tetrapeptide antagonist [3H]TIPP.
AB  - Slide-binding and autoradiographic studies were performed on cryostat sections
      from brains of adult Sprague-Dawley rats and BALB C mice to describe the binding
      characteristics of the tetrapeptide [3H]TIPP, an antagonist with high specificity
      and affinity for the delta opioid receptors. Steady-state binding of [3H]TIPP to
      cryostat sections of brain paste was reached in 120-180 min of incubation.
      Specific [3H]TIPP binding resulted in maximal numbers of binding sites (Bmax) of
      15.59 and 23.91 fmol/mg protein, and dissociation constants (Kd) of 0.46 and 0.85
      nM for rat and mouse brain paste sections, respectively. TIPP displayed the
      highest affinity for delta opioid receptors in inhibiting specific [3H]TIPP
      binding, with IC50 values of 0.82 nM and 0.14 nM in rat and mouse brain sections,
      respectively. While DPDPE was also effective in displacing the specific binding
      of [3H]TIPP (IC50 = 3.18 +/- 0.53 nM and 0.63 +/- 0.42 nM in rat and mouse brain
      paste sections, respectively), other subclass-selective or nonopioid ligands were
      much less effective, or ineffective. Autoradiographic localization of [3H]TIPP
      binding revealed the characteristic distribution of delta opioid receptors in
      both species. In consequence of its antagonistic nature, and of its unnatural
      amino acid residue, which makes this ligand more resistant to biodegradation,
      [3H]TIPP is a superior ligand for evaluation of the binding characteristics and
      autoradiogaphic distribution of the delta opioid receptors.

PMID- 9768877
TI  - An ex vivo evaluation of regulatory role of biogenic amines in rat seminal
      vesicle after pharmacological manipulation.
AB  - We studied the neural regulation of seminal vesicles (SV) by determining the
      changes of intraluminal pressure of rat SV in response to an electric stimulation
      of the lesser splanchnic nerve (LSN). After pharmacological manipulation with
      neurotoxin, the contents of monoamines and their metabolites in SV were
      estimated. In rats receiving electric stimulation of the LSN, an increase of
      intraluminal pressure was obtained with a reduction of the serotonergic turnover
      rate in SV. An intraperitoneal injection of DSP-4 (100 mg/kg), the noradrenergic
      neurotoxin, into rats decreased the level of norepinephrine (NE) in SV
      significantly but did not influence this functional response. Also, the
      intraluminal pressure was lowered by an intrathecal injection of 6-OHDA (20
      microg/rat) to denervate spinal monoaminergic nerves in rats although the
      contents of monoamines in SV were not changed. This indicates that noradrenergic
      neurotransmission appears unimportant in this regulation. The lowering of
      intraluminal pressure in rats by 6-OHDA is mainly related to an attenuation of
      dopaminergic neuroregulation from the decrease of turnover rate of DA. Otherwise,
      an intrathecal injection of 5,7-DHT (60 microg/rat) to abolish spinal
      serotonergic nerves did not influence the level of monoamines in SV but increased
      the intraluminal pressure indicating an involvement of inhibitory regulation from
      spinal serotonergic pathway. These results suggest that contraction by electric
      stimulation of the LSN in Wistar rat SV is mainly regulated by the dopaminergic
      nervous pathway and an inhibitory regulation of the serotonergic nervous pathway
      from spinal cord while the noradrenergic nervous system seems unimportant for
      this regulation.

PMID- 9768878
TI  - Antagonism of kynurenic acid to anxiogens in mice.
AB  - In a dark-light chamber in mice, kynurenic acid (KYNA, 200 mg/kg, i.p.), an
      endogenous neuroactive metabolite of tryptophan, attenuated the most stable
      effect of anxiogens in this model of anxiety--a decrease in the rate of leanings
      out of the dark compartment --induced by caffeine, pentylenetetrazole and
      yohimbine, but not by beta-phenylethylamine (PEA). KYNA by itself did not alter
      behavior of mice in the chamber, in contrast to what has been observed in an
      elevated plus-maze, another model of anxiety, where KYNA had an anxiolytic
      pharmacological profile.

PMID- 9768879
TI  - Femoral stem fixation. An engineering interpretation of the long-term outcome of
      Charnley and Exeter stems.
AB  - The excellent long-term results for the first-generation Charnley stem may not
      apply to later versions with flanges. It seems possible that the early design
      functioned as a taper-slip system, as accepted in the Exeter prosthesis.
      Comparison with the requirements for the alternative composite-beam system for
      the femoral component shows considerable differences that have important
      implications. These include design, surface finish, cementing technique and the
      interpretation of radiological signs of loosening. A distinction should be made
      between the requirements for the successful use of the two different engineering
      systems.

PMID- 9768880
TI  - The treatment of subluxation of the hip in children over the age of four years.
AB  - Subluxation of the hip presenting for the first time in a child over the age of
      four years is rare. We report ten cases treated over nearly 11 years by the
      senior author (JAF). We describe the surgical procedures and the results, at
      maturity, of nine of the ten patients. At a mean follow-up of nearly nine years,
      the clinical outcome was good in all ten children by the criteria of Ponseti.
      Radiological assessment showed that three hips remained subluxed, and that four
      had avascular necrosis of the physis. We advise a one-stage procedure, correcting
      both the femur and acetabulum.

PMID- 9768881
TI  - Residual deformity in congenital radial club hands after previous centralisation
      of the wrist. Ulnar lengthening and correction by the Ilizarov method.
AB  - We used the Ilizarov method in seven patients with severe congenital radial club
      hands who had had previous wrist surgery, to correct residual shortening and
      bowing of the ulna together with recurrent wrist deformity. The mean age at
      operation was 6.5 years. The mean ulnar shortening was 5.3 cm and the mean
      angular deformity 42 degrees. The mean length gained was 51% of the original
      ulna. The mean healing index was 46.9 days (29.8 to 64.0). The ratio of the
      length of the lengthened ulna to the normal side improved on average from 64% to
      95%. The angular deformity was initially completely corrected in six out of seven
      patients. The length ratio, however, decreased to 83% at the final follow-up. In
      four patients, the angular deformity partially recurred. We recommend correction
      of congenital radial club hand by staged procedures. The first is centralisation
      and stabilisation of the wrist and the second lengthening of the ulna and
      correction of the angular deformity using the Ilizarov method.

PMID- 9768882
TI  - Cat-scratch disease osteomyelitis from a dog scratch.
AB  - Osteomyelitis is a rare manifestation of cat-scratch disease in patients who do
      not have AIDS. The clinical presentation and non-specific subacute course of the
      disease make diagnosis difficult. We present a child with osteomyelitis of a
      metacarpal following a dog scratch. Bartonella henselae was found to be the
      aetiological agent. The bone healed after treatment with antibiotics. Increased
      awareness and a comprehensive medical history are needed to identify patients
      with suspected Bartonella henselae osteomyelitis.

PMID- 9768883
TI  - Progressive osseous heteroplasia. Report of a family.
AB  - We report a case of progressive osseous heteroplasia in a female infant who had
      progressive ossification of the skin and deep connective tissues. Isolated dermal
      ossification is present in her father and younger sister suggesting an autosomal
      dominant mode of inheritance with variable expressivity or possible somatic
      mosaicism. This report of a family with progressive osseous heteroplasia
      contributes to the understanding of this uncommon genetic disorder, which must be
      distinguished from fibrodysplasia ossificans progressiva and Albright's
      hereditary osteodystrophy. The paucity of familial cases of progressive osseous
      heteroplasia currently limits the use of a genome-wide linkage analysis, but
      linkage exclusion analysis with promising candidate genes is a possibility.

PMID- 9768884
TI  - Severe progressive deformities after limb lengthening in type-II fibular
      hemimelia.
AB  - Until recently the accepted treatment of choice for severe type-II fibular
      hemimelia has been Syme's or Boyd's amputation. The alternative of distraction
      lengthening using the Ilizarov technique is now available. We report three
      patients (four limbs) with type-II fibular hemimelia who were treated by the
      Ilizarov technique and followed up for two to six years. Severe progressive
      procurvatum and valgus deformity of the tibia and valgus deformity and lateral
      subluxation of the ankle were found in all four limbs. Multiple additional soft
      tissue and bony surgery was necessary. In view of these problems we feel that
      reappraisal of the indications for lengthening in type-II fibular hemimelia is
      necessary.

PMID- 9768885
TI  - Coregistration imaging of the foot. A new localisation technique.
AB  - We describe a new technique, known as coregistration imaging, which superimposes
      99mTc isotope bone scans on to plain radiographs. We used the technique
      selectively in cases in which the nuclear medicine physician, who reported the
      isotope scan, had difficulty in localising the anatomical site of the
      abnormality. In the forefoot, coregistration of isotope scans did not help to
      localise pathology; the scan alone gave sufficient detail. In 17 patients with
      pain in the hind- and midfoot, isotope scanning identified eight sites of
      abnormality in those with normal radiographs. In those with more than one
      abnormality on plain radiographs the isotope scan eliminated 12 sites of
      suspicion. Coregistration of the images significantly increased the certainty of
      localisation of disease (p < 0.001). We recommend the selective use of
      coregistration scanning as a useful technique for investigating patients with
      pain in the foot and ankle.

PMID- 9768886
TI  - Operative reconstruction after transverse rupture of the tendons of both peroneus
      longus and brevis. Surgical reconstruction by transfer of the flexor digitorum
      longus tendon.
AB  - Rupture of the tendons of both peroneus longus and peroneus brevis results in
      considerable disability. We have performed transfer of flexor digitorum longus
      (FDL) to peroneus brevis in two patients with lateral instability of the hindfoot
      due to chronic transverse tears of both tendons for which end-to-end repair was
      not possible. Both patients had excellent function when reviewed after eight and
      six years, respectively, with no symptoms. CT showed a normal appearance of the
      FDL in both patients, but the peroneal muscles looked abnormal. Transfer of the
      FDL provides a reliable solution to lateral instability of the hindfoot resulting
      from loss of function of both peronei.

PMID- 9768887
TI  - Subtalar arthrography in acute injuries of the calcaneofibular ligament.
AB  - We treated 43 acute tears of the calcaneofibular ligament by operation in 43
      patients after subtalar arthrography. There were 22 men and 21 women with a mean
      age of 22.3 years (14 to 61). Anteroposterior (AP), lateral and oblique views
      were obtained with the foot in 45 degrees of internal rotation and the ankle in
      the neutral position. Any communication or leakage to the ankle, tendon sheaths,
      subcutaneous tissue and sinus tarsi was recorded. We examined an oblique view of
      the microrecess along the interosseous ligament and an AP view of the lateral
      recess just under the distal end of the fibula. We also studied a control group
      of 27 patients with isolated injuries of the anterior talofibular ligament
      without rupture of the calcaneofibular ligament. The findings in the two groups
      were significantly different when examined for leakage to the ankle (p=0.0002),
      to the peroneal tendon sheaths (p=0.0347) and to the subcutaneous tissue
      (p=0.0222), absence of the microrecess (p=0.0055) and presence of the lateral
      recess (p=0.0012). Many ankle sprains which involve tearing of the
      calcaneofibular ligament are accompanied by injuries of the subtalar joint.
      Combined injuries of the anterior talofibular ligament and calcaneofibular
      ligament, and isolated injury of the anterior talofibular ligament should be
      differentiated.

PMID- 9768888
TI  - Second fracture of the distal humerus after varus malunion of a supracondylar
      fracture in children.
AB  - Nine children sustained a second fracture of the distal humerus after union of an
      ipsilateral supracondylar fracture which had healed with cubitus varus. There
      were eight boys and one girl with a mean age of five years (1 to 8) at the time
      of the second fracture which occurred at a mean of 1.5 years after the first. In
      all patients, the second fracture was an epiphyseal injury of the distal humerus,
      either associated with a fracture of the lateral metaphysis below the site of the
      previous supracondylar fracture, or a fracture-separation of the entire distal
      humeral epiphysis. This suggests that the physis and epiphysis tend to be more
      subject to injury than the metaphysis of the distal humerus in children who have
      had a previous supracondylar fracture with varus malunion.

PMID- 9768889
TI  - Open reduction, internal fixation and fibular autografting for neglected fracture
      of the femoral neck.
AB  - Neglected fractures of the femoral neck, common in young adults in underdeveloped
      countries, may be complicated by nonunion or avascular necrosis (AVN). We treated
      52 cases by open reduction, fixation by compression screw and a free fibular
      graft. The mean delay between injury and operation was 5.1 months. Of 40
      fractures assessed at a mean of 58.8 months (24 to 153), 38 were found to be
      united and two, owing to surgical errors, were not. Seven of eight heads which
      were avascular before operation revascularised without collapse, while seven
      others developed AVN after the procedure. At the last follow-up considerable
      collapse was apparent in five femoral heads, and 11 hips had developed coxa vara.
      The fibular graft had fractured in four cases. The hip had been penetrated by the
      screw in six cases and by the graft in three. Hip function was excellent in seven
      patients, good in 21 and fair in seven. Five patients had poor results.
      Incorporation of the fibular graft was seen after four years: in many cases the
      graft had been almost completely resorbed. We recommend this procedure for the
      treatment of neglected fractures of the neck of the femur in young adults to
      reduce resorption of the neck, AVN and nonunion.

PMID- 9768890
TI  - Post-traumatic contracture of the elbow. Operative release using a lateral
      collateral ligament sparing approach.
AB  - We performed a lateral approach for the release of post-traumatic stiffness of
      the elbow in 22 patients using a modified technique designed to spare the lateral
      ligaments. They were reviewed after a mean interval of 26 months. The total
      humeroulnar joint movement had increased from a mean of 74 degrees to 129 degrees
      and forearm rotation from a mean of 135 degrees to 159 degrees. Both pain and
      function in the elbow had improved significantly. This modified lateral approach
      allows release of post-traumatic contracture without disruption of the lateral
      collateral ligament or the origins of the extensor tendon at the lateral
      epicondyle of the humerus. The advantages include a simplified surgical
      procedure, less operative morbidity, and unrestricted rehabilitation.

PMID- 9768891
TI  - Open acromioplasty does not prevent the progression of an impingement syndrome to
      a tear. Nine-year follow-up of 96 cases.
AB  - We performed open acromioplasty for intractable impingement syndrome on 96
      shoulders (93 patients) with an intact rotator cuff. All the shoulders were
      examined by ultrasound after a mean interval of nine years. Those showing
      pathological findings, a poor or fair subjective result, or deterioration of the
      primary excellent outcome had MRI and/or arthrography. The mean Constant score
      for the affected shoulders was 70 points and that for 48 non-involved, symptom
      free shoulders, 84 points. The subjective outcome was excellent in 45, good in
      24, fair in 18 and poor in 9 shoulders. Complete tears were found in 12 shoulders
      and partial tears in seven. A total of 14 shoulders was symptom-free after
      acromioplasty, but after an average of five years became painful again and showed
      deterioration. Of these, six had complete tears and four partial tears of the
      cuff. The tear rate was 4% in shoulders initially judged to be excellent, 25% in
      good, 33% in fair and 55% in poor shoulders. The tear rate was 71% in shoulders
      which subsequently deteriorated. The incidence was higher in men (25%) than in
      women (11%). We conclude that a tear of the rotator cuff may appear after
      acromioplasty, although there was no evidence of a tear at the time of operation.
      This is usually the reason for deterioration in a shoulder with an initially good
      operative outcome.

PMID- 9768892
TI  - Osteotomy of the radius and ulna for the Madelung deformity.
AB  - The Madelung deformity can result in pain and decreased function of the wrist and
      hand. None of the surgical techniques available has been shown consistently to
      improve grip strength, range of movement or relieve pain. In this prospective
      study we have treated 18 patients with the Madelung deformity (25 wrists) by
      wedge subtraction osteotomy of the radius and shortening of the ulna. Our results
      show statistically significant improvement in grip strength and range of movement
      of the wrist and forearm. Pain improved in 80% of the patients and 88% were
      satisfied with the appearance. One patient had a wound infection and another
      developed reflex sympathetic dystrophy. Two had some recurrence due to continued
      growth of the ulna and it is recommended that the procedure be delayed until
      skeletal maturity, or else combined with epiphysiodesis of the ulna.

PMID- 9768893
TI  - Ipsilateral recurrent lumbar disc herniation. A prospective, controlled study.
AB  - We analysed prospectively 26 patients who had revision operations for ipsilateral
      recurrent radicular pain after a period of pain relief of more than six months
      following primary discectomy. They were assessed before the initial operation,
      between the two procedures and at a minimum of two years after reoperation. MRI
      was performed before primary discectomy and reoperation. Fifty consecutive
      patients who had a disc excision during the study period but did not have
      recurrent radicular pain, were analysed as a control group. Of the study group
      42% related the onset of recurrent radicular pain to an isolated injury or a
      precipitating event, but none of the control group did so (p < 0.001). T2
      weighted MRI performed before primary discectomy showed that patients in the
      study group had significantly more severe disc degeneration compared with the
      control group (p=0.02). Intraoperative findings revealed recurrent disc
      herniation in 24 patients and bulging of the disc in two, one of whom also had
      lateral stenosis. Epidural scarring was found to be abundant, intraoperatively
      and on MRI, in eight and in nine patients, respectively. At the last follow-up,
      the clinical outcome was satisfactory in 85% of patients in the study group and
      in 88% of the control group (p > 0.05). Work or daily activities had been resumed
      at the same level as before the onset of symptoms by 81% of the patients in the
      study group and 84% of the control group. No correlation was found between the
      amount of epidural fibrosis, as seen intraoperatively and on MRI, and the result
      of surgery. The recurrence of radicular pain caused no significant changes in the
      psychological profile compared with the assessment before the primary discectomy.

PMID- 9768894
TI  - Changes in the disc space after fractures of the thoracolumbar spine.
AB  - We have studied the intervertebral discs adjacent to fractured vertebral bodies
      using MRI in 63 patients at a minimum of 18 months after injury. There were 75
      thoracolumbar fractures of which 26 were treated conservatively and 37 by
      posterior reduction and fusion with an AO internal fixator. We identified six
      different types of disc using criteria based on the morphology and the intensity
      of the MRI signal. The inter- and intraobserver variability of this system was
      good. Most of the discs showed predominantly morphological changes with no
      variation in signal intensity. Some disc types were associated with progressive
      kyphosis in patients treated conservatively. In those managed by operation,
      recurrent kyphosis appeared to result from creeping of the disc in the central
      depression of the bony endplate rather than from disc degeneration. Changes in
      the disc space after posterior fixation should not be seen as a form of chronic
      instability but as a redistribution of the disc tissue in the changed morphology
      of the space after fractures of the endplate.

PMID- 9768895
TI  - Fracture-dislocation of the fifth lumbar vertebra. A new classification.
AB  - We have studied fracture-dislocation of the fifth lumbar vertebra in seven
      patients and reviewed 50 previously reported cases. Based on this information, we
      have classified the injury into five types: type 1, unilateral lumbosacral facet
      dislocation with or without facet fracture; type 2, bilateral lumbosacral facet
      dislocation with or without facet fracture; type 3, unilateral lumbosacral facet
      dislocation and contralateral lumbosacral facet fracture; type 4, dislocation of
      the body of L5 with bilateral fracture of the pars interarticularis; and type 5,
      dislocation of the body of L5 with fracture of the body and/or pedicle, with or
      without injury of the lamina and/or facet. Conservative treatment of fracture
      dislocation of L5 is generally not effective because the lesion is fundamentally
      unstable. Planning of the operation should be made on the basis of the various
      types of injury.

PMID- 9768896
TI  - Radiculopathy after laminectomy for cervical compression myelopathy.
AB  - Postoperative radiculopathy is a complication of posterior cervical decompression
      associated with tethering of the nerve root. We reviewed retrospectively 287
      consecutive patients with cervical compression myelopathy who had been treated by
      multilevel cervical laminectomy and identified 37 (12.9%) with postoperative
      radiculopathy. There were 27 men and ten women with a mean age of 56 years at the
      time of operation. The diagnosis was either cervical spondylosis (25 patients) or
      ossification of the posterior longitudinal ligament (12 patients). Radiculopathy
      was observed from four hours to six days after surgery. The most frequent pattern
      of paralysis was involvement of the C5 and C6 roots of the motor-dominant type.
      The mean time for recovery was 5.4 months (two weeks to three years). The results
      at follow-up showed that the rate of motor recovery was negatively related to the
      duration of complete recovery of postoperative radiculopathy (gamma=-0.832, p <
      0.01) and that patients with spondylotic myelopathy had a significantly better
      rate of clinical recovery than those with ossification of the posterior
      longitudinal ligament (t=2.960, p < 0.01). Postoperative radiculopathy may be
      prevented by carrying out an anterior decompression in conjunction with spinal
      fusion, which will achieve stabilisation and directly remove compression of the
      cord at multiple levels.

PMID- 9768897
TI  - Total knee arthroplasty with the PFC system. Results at a minimum of ten years
      and survivorship analysis.
AB  - A consecutive series of 235 total knee arthroplasties using the PFC system was
      followed prospectively for at least ten years in 186 patients. The operation was
      for osteoarthritis in 150 knees, for rheumatoid arthritis in 83, and for Paget's
      disease and femoral osteonecrosis in one knee each. At the latest review 56
      patients had died, five were too ill to assess and three could not be traced. The
      PFC knee replacement utilised was a non-conforming posterior-cruciate-retaining
      prosthesis with a polyethylene insert which is flat in the sagittal plane. The
      patella was resurfaced using a metal-backed component in 170 cases, but later in
      the series we used an all-polyethylene component in 22 knees; 43 patellae were
      not resurfaced. The survival without need for reoperation for any reason was 90%
      at ten years. Nineteen revisions were component-related due to failure of nine
      metal-backed patellae, nine polyethylene inserts, and one unresurfaced patella;
      two reoperations were for synovectomy (one for recurrent haemarthrosis and one
      for recurrent rheumatoid synovitis) and three were for metastatic joint
      infection. There were no revisions for aseptic loosening of femoral or tibial
      components, or the all-polyethylene patellar replacement. The PFC system provides
      good and predictable results in tricompartmental arthritis of the knee. Loosening
      appeared to be negligible, but there were wear-related problems in 8%. The change
      from a metal-backed patella and an increase in the contact area of the tibial
      insert should provide further improvement by minimising wear.

PMID- 9768898
TI  - Replacement arthroplasty of the valgus knee. A modified lateral capsular approach
      with repositioning of vastus lateralis.
AB  - Total knee arthroplasty (TKR) using a medial capsular approach gives worse
      results in arthritic knees with valgus deformity than in those in varus, usually
      because of swelling, poor wound healing and stiffness, instability, recurrent
      valgus deformity and poor patellar tracking. A technique for replacement TKR of
      valgus knees using a lateral capsular approach was described several years ago,
      but was not routinely adopted because of the difficulties with and complexity of
      the procedure which included deliberate elevation of the tibial tubercle. In
      order to avoid this we have modified and simplified the procedure. Our
      preliminary results suggest that this lateral approach is safe and may give a
      better outcome than that through the medial capsule for the replacement of valgus
      knees.

PMID- 9768899
TI  - Unicompartmental or total knee replacement? Five-year results of a prospective,
      randomised trial of 102 osteoarthritic knees with unicompartmental arthritis.
AB  - We randomised 102 knees suitable for a unicompartmental replacement to receive
      either a unicompartmental (UKR) or total knee replacement (TKR) after arthrotomy.
      Both groups were well matched with a predominance of females and a mean age of 69
      years. Patients in the UKR group showed less perioperative morbidity, but
      regained knee movement more rapidly and were discharged from hospital sooner. At
      five years, two UKRs and one TKR had been revised; another TKR was radiologically
      loose. All other knees appeared to be clinically and radiologically sound. Pain
      relief was good in both groups but the number of knees able to flex > or =120
      degrees was significantly higher in the UKR group (p < 0.001) and there were more
      excellent results in this group. Our findings have shown that UKR gives better
      results than TKR and that this superiority is maintained for at least five years.

PMID- 9768900
TI  - Acute compartment syndrome of the thigh after joint replacement with
      anticoagulation.
AB  - We describe three patients with a compartment syndrome of the thigh, two after
      total hip replacement and one after total knee replacement. Two of the patients
      were fully anticoagulated. A compartment syndrome of the thigh is a rare, but
      important complication of joint replacement surgery if patients are receiving
      anticoagulants. Close observation is needed and when indicated monitoring of the
      intracompartmental pressure should be done. Early recognition of the signs and
      symptoms of an acute compartment syndrome and knowledge of the anatomy of the
      compartments of the thigh will help in the diagnosis and treatment of this
      potentially devastating complication.

PMID- 9768901
TI  - A ported, proximally-cemented femoral stem for total hip arthroplasty.
      Development and clinical application.
AB  - We describe the development and early clinical application of a ported,
      proximally-cemented titanium stem for cemented total hip arthroplasty. PMMA bone
      cement is delivered to the proximal femur under pressure after the stem has been
      positioned within the femoral canal. A mid-stem cement occluder contains the
      cement to the proximal stem only. A tapered body is incorporated in the design of
      the stem to reduce the structural stiffness and hence the degree of stress
      shielding within the reconstructed joint. We performed preclinical studies to
      measure the reduction in porosity and the pressurisation achieved. The porosity,
      as measured by the void percentage within the cured cement mantle, was reduced by
      more than 50% and there was an almost threefold increase in the mean pressure.
      Mechanical testing of the stem, using a three-point bend test, showed that the
      addition of cement injection ports on the anterior and posterior sides of the
      body of the proximal stem did not reduce its strength. Finite-element analysis
      indicated that, compared with a fully-cemented conventional stem, there was no
      change in the stresses within the cement mantle. In a series of 40 proximally
      cemented stems followed for up to six years (mean 51 months) the mean Harris hip
      score was 91, and 85% of patients had good or excellent results. There was
      excellent pain relief, an increased level of activity and good patient
      satisfaction. One mechanical failure of the stem required revision at three years
      after implantation. The early results indicate that the clinical performance was
      equal to that achieved with other modern cemented stems. Radiological evaluation
      showed excellent results with no evidence of stress shielding. Further follow-up
      will determine if long-term stress shielding is reduced and if revision is made
      easier by the absence of a distal cement mantle.

PMID- 9768902
TI  - Incisional cellulitis after total hip replacement.
AB  - We report 16 cases of erythematous eruption on the skin within the flaps of the
      surgical incision after primary total hip replacement over an eight-year period.
      The symptoms began within nine months of operation in 13 hips, and two to three
      years after in three. Four patients had recurrent episodes. All were treated with
      antibiotics (15 intravenous, one oral) with complete resolution of the eruption
      within one to six days. The mean follow-up after the last episode of cellulitis
      was 27 months (14 to 76). There were no cases of periprosthetic sepsis or other
      sequelae.

PMID- 9768903
TI  - Changes in the expression of Fas, osteonectin and osteocalcin with age in the
      rabbit growth plate.
AB  - Chondrocytes of the growth plate are generally assumed to undergo apoptosis, but
      the mechanisms which induce this cell death are not known. The Fas receptor is a
      mediator of the apoptotic signal in some systems. We studied its expression in
      situ in growth plates of rabbits aged from five to 20 weeks. In addition, we
      investigated the immunolocalisation in the growth plates of the bone proteins,
      osteonectin and osteocalcin, and the changes in their expression with age. The
      Fas-positive chondrocytes were found mostly in the hypertrophic zone, as were the
      osteonectin-positive and osteocalcin-positive cells. The percentage of Fas
      positive cells increased with age whereas little change was found in the number
      of osteonectin-positive and osteocalcin-positive chondrocytes. Many of the Fas
      positive chondrocytes were also TUNEL-positive. This strongly suggests that
      apoptosis in the growth plate is mediated through the Fas system. Double
      immunostaining for osteocalcin and Fas showed that not all hypertrophic
      chondrocytes were of the same cell type. Some chondrocytes stained for
      osteocalcin only, others for Fas only, while some were positive for both.

PMID- 9768904
TI  - Anti-inflammatory properties of titanium in the joint environment. An
      experimental study in rats.
AB  - Little is known about the tissue reactions to various implant materials which
      coincide with an inflammatory reaction. We used the avridine arthritis rat model
      to evaluate the tissue response in the synovial, interstitial and subcutaneous
      tissues after implant insertion. Quantitative immunohistochemistry showed that
      normal joint synovial tissue is dominated by ED2-positive resident macrophages.
      Polyethylene implants induced a much stronger foreign-body reaction than titanium
      implants, as measured by the number of interfacial ED1-positive macrophages. The
      tissue response to titanium and polyethylene was also vastly different in
      arthritic synovial tissue compared with control tissue. It is likely that these
      biomaterials interact differently with inflammatory cells or intermediary
      compounds. It may be that arthritic synovial tissue produces reactive oxygen
      intermediates (free radicals) with which titanium has a unique anti-inflammatory
      interaction in vitro.

PMID- 9768905
TI  - Quantification of third-body damage and its effect on UHMWPE wear with different
      types of femoral head.
AB  - We examined stainless-steel, cobalt-chrome, titanium and alumina and zirconia
      ceramic femoral heads retrieved at revision surgery. All the heads had
      articulated against ultra-high-molecular-weight-polyethylene (UHMWPE) acetabular
      cups. We studied the simulation of third-body damage and the wear of UHMWPE
      against the various materials used for the heads. The surfaces of the retrieved
      heads were analysed using a two-dimensional contacting profilometer. Third-body
      damage was characterised by the mean height of the scratches above the mean line
      (Rpm). The alumina ceramic and zirconia ceramic retrieved heads were found to
      have significantly less damage. In laboratory studies the ceramics were also more
      resistant to simulated third-body damage than the metal alloys. We studied the
      wear of UHMWPE against the damaged counterfaces in simple configuration tests.
      The damaged ceramics produced less polyethylene wear than the damaged metal
      counterfaces. The wear factor of UHMWPE against the damaged materials was
      dependent on the amount of damage to the counterface (Rp). Our study has shown
      the benefit of using the harder and more damage-resistant ceramic materials for
      femoral heads.

PMID- 9768906
TI  - In vitro measurement of patellofemoral force after three types of knee
      replacement.
AB  - Using a new, non-invasive method, we measured the patellofemoral force (PFF) in
      cadaver knees mounted in a rig to simulate weight-bearing. The PFF was measured
      from 20 degrees to 120 degrees of flexion before and after implanting three
      designs of knee prosthesis. Medial unicompartmental arthroplasty with a meniscal
      bearing prosthesis and with retention of both cruciate ligaments caused no
      significant change in the PFF. After arthroplasty with a posterior-cruciate
      retaining prosthesis and division of the anterior cruciate ligament, the PFF
      decreased in extension and increased by 20% in flexion. Implantation of a
      posterior stabilised prosthesis and division of both cruciate ligaments produced
      a decrease in the PFF in extension but maintained normal load in flexion. There
      was a direct relationship between the PFF and the angle made with the patellar
      tendon and the long axis of the tibia. The abnormalities of the patellar tendon
      angle which resulted from implantation of the two total prostheses explain the
      observed changes in the PFF and show how the mechanics of the patellofemoral
      joint depend upon the kinematics of the tibiofemoral articulation.

PMID- 9768907
TI  - Dupuytren's disease and frozen shoulder induced by treatment with a matrix
      metalloproteinase inhibitor.
AB  - In a series of 12 patients with inoperable gastric carcinoma who had treatment
      with a synthetic matrix metalloproteinase inhibitor (Marimastat) for more than
      one month, six developed a frozen shoulder or a condition resembling Dupuytren's
      disease. This suggests that the matrix metalloproteinases, a family of naturally
      occurring proteinases, may be involved in the pathogenesis of these two
      conditions. Our observation opens avenues for further research which could lead
      to local or systemic therapeutic interventions for frozen shoulder and
      Dupuytren's disease.

PMID- 9768908
TI  - C-reactive protein level after total hip and total knee replacement.
AB  - Our study has determined the response of C-reactive protein (CRP) after total
      knee replacement (TKR). The peak level occurs on the second postoperative day and
      is significantly greater than that after total hip replacement (THR). The level
      returns to normal at similar times after both procedures. The physiological
      response to TKR as measured by the area under the CRP/time curve is significantly
      greater than that after THR. Rising CRP levels after the third postoperative day
      may indicate a complication of surgery such as infection.

PMID- 9768909
TI  - Bone-resorbing cytokines in serum of patients with aseptic loosening of hip
      prostheses.
AB  - Our aim was to determine if the serum levels of bone-resorbing cytokines (IL
      1beta, TNF-alpha, IL-6, GM-CSF) are altered in patients with aseptic loosening of
      a total hip prosthesis, and if such levels are influenced by the type of implant.
      We determined cytokine levels in sera from 35 patients before revision for failed
      total hip arthroplasty and compared them with those in 25 healthy donors. We also
      assessed the soluble receptor of interleukin-2 (sIL-2r) in serum as an indication
      of a specific immune reaction against the implant. Our findings showed that the
      sIL-2r and TNF-alpha serum level did not change. The IL-6 level was not
      significantly altered, but was higher in patients with TiAIV prostheses than in
      those with a CrCoMo implant and in patients with cemented prostheses. The IL
      1beta level was found to be higher in those with a TiAIV cemented prosthesis than
      in the control group (p=0.0001) and other groups of patients (p=0.003 v
      uncemented TiAIV, p=0.01 v cemented CrCoMo, p=0.001 v uncemented CrCoMo). The GM
      CSF level significantly increased in patients compared with healthy subjects
      (p=0.008), and it was higher in those with cemented than with uncemented implants
      (p=0.01). Only patients with cementless CrCoMo prostheses had levels of GM-CSF
      similar to those of the control group. The highest GM-CSF concentrations were
      observed in patients treated with non-steroidal anti-inflammatory drugs (NSAIDs)
      in the last months before revision (p=0.04). In addition, when massive osteolysis
      was observed, the level of GM-CSF tended to decrease to that of the control
      group.

PMID- 9768910
TI  - Autologous perichondral tissue for meniscal replacement.
AB  - Our aim was to examine the potential of autologous perichondral tissue to form a
      meniscal replacement. In 18 mature sheep we performed a complete medial
      meniscectomy. The animals were then divided into two groups: 12 had a meniscal
      replacement using strips of autologous perichondral tissue explanted from the
      lower rib (group G) and six (group C) served as a control group without a
      meniscal replacement. In all animals restriction from weight-bearing was achieved
      by means of transection and partial resection of tendo Achillis. Six animals
      (four from group G and two from group C) were each killed at 3, 6 and 12 months.
      The grafts and the underlying articular cartilage were removed and studied by
      gross macroscopic examination, light microscopy, SEM, polarised light
      examination, and by biomechanical tests. In all the transplanted animals a new
      perichondral meniscus developed. After three months the transplants resembled
      normal menisci in size and thickness, while in the control animals only small
      rims of spontaneously grown tissue were seen. Microscopically, the perichondral
      menisci showed a normal orientation of collagen fibres and normal cellular
      characteristics, but in the central region, areas of calcification disturbed the
      regular tissue differentiation. Healing tissue in control animals lacked the
      normal fibre orientation and cellularity. SEM of perichondral menisci showed
      surface characteristics similar to those of normal sheep menisci without fissures
      and lacerations; the control specimens had these defects. The femoral and tibial
      cartilage in contact with the new menisci had normal surface characteristics
      apart from one animal with slight surface irregularities. Control animals showed
      superficial lesions after three months which increased at six to 12 months
      postoperatively. Microangiography of the newly grown tissue demonstrated a less
      intense vascularisation after three months when compared with normal menisci. The
      failure stress and tensile modulus of perichondral menisci were significantly
      lower than those of normal contralateral menisci, and spontaneously regenerated
      tissue in meniscectomised animals had even lower values. There were no
      significant differences in values between newly grown perichondral menisci and
      spontaneously grown tissue.

PMID- 9768911
TI  - Effects of particulate debris on macrophage-dependent fibroblast stimulation in
      coculture.
AB  - The interactions between the different cell types in periprosthetic tissue are
      still unclear. We used a non-contact coculture model to investigate the effects
      of polymethylmethacrylate (PMMA) particles and human macrophage-derived soluble
      mediators on fibroblast activation. Macrophages were either exposed or not
      exposed to phagocytosable PMMA particles, but fibroblasts were not. Increasing
      numbers of macrophages were tested in cocultures in which the fibroblast cell
      number was held constant and cultures of macrophages alone were used for
      comparison of cytokine release. We used the release of interleukin-1 beta (IL
      1beta), interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-alpha), lysosomal
      enzyme and metalloproteinase activity to assess the cultivation of macrophages
      and fibroblasts. In cocultures, IL-6 release was increased 100-fold for both
      unchallenged and particle-challenged cultures when compared with macrophage
      cultures alone. Furthermore, particle-challenged cocultures had threefold higher
      IL-6 levels than unchallenged cocultures. Release of TNF-alpha was similar in
      cocultures and in macrophage cultures. IL-1beta release in cocultures was
      independent of the macrophage-fibroblast ratio. Lysosomal enzyme activity and
      metalloproteinase activity were increased in cocultures. Our data show that
      macrophages and fibroblasts in coculture significantly increase the release of IL
      6 and to a less degree other inflammatory mediators; particle exposure
      accentuates this effect. This suggests that macrophage accumulation in fibrous
      tissue may lead to elevated IL-6 levels that are much higher than those caused by
      particle activation of macrophages alone. This macrophage-fibroblast interaction
      represents a novel concept for the initiation and maintenance of the inflammatory
      process in periprosthetic membranes.

PMID- 9768912
TI  - Superolateral wear of the acetabulum.

PMID- 9768913
TI  - The anatomy of acute scaphoid fractures.

PMID- 9768914
TI  - Effect of particulate cobalt, chromium and cobalt-chromium alloy on human
      osteoblast-like cells in vitro.

PMID- 9768915
TI  - Diagnostic value of intra-articular anaesthetic in primary osteoarthritis of the
      hip.

PMID- 9768916
TI  - Thoracic surgeons and tobacco: past failures and present opportunity.
AB  - Thoracic surgeons play a major role in the treatment of tobacco-caused disease.
      Historically, thoracic surgeons have been committed investigators of tobacco
      caused disease and activists for tobacco control reform. This editorial reviews
      and comments on the current activity of American thoracic surgeons, thoracic
      surgical societies, and journals in these areas. Thoracic surgeons have been
      remiss in their individual and collective public health responsibility to inform
      the public and advocate tobacco control reforms. We must commit to a more
      energetic effort.

PMID- 9768917
TI  - Complementary use of antegrade and retrograde cardioplegia.

PMID- 9768918
TI  - Aortic valve replacement for octogenarians: are small valves bad?
AB  - BACKGROUND: As the population ages, more octogenarians become candidates for
      aortic valve replacement. Many octogenarians, particularly women, have a small
      aortic annulus and there is uncertainty as to the optimal management of this
      situation in that age group. METHOD: To examine this issue, we reviewed 248
      octogenarians (mean age, 82.6 +/- 2.3 years; 58% men) who underwent primary
      isolated aortic valve replacement (n = 99), or aortic valve replacement and
      coronary revascularization (n = 149), between 1980 and 1995. Nineteen-millimeter
      valves were used in 26% of the patients. RESULTS: In-hospital mortality was 8.9%,
      5% for aortic valve replacement alone and 11.4% for aortic valve replacement and
      coronary revascularization. It was 12.5% for the 19-mm size valves compared with
      7.7% for the bigger size valves (p = 0.24). Follow-up (mean interval, 4.4 years)
      demonstrated survival for all patients of 85%, 60%, and 30% and survival free
      from cardiovascular events of 80%, 45%, and 21% at 1, 5, and 10 postoperative
      years, respectively. Multivariate analysis identified triple-vessel disease and
      preoperative congestive heart failure as associated with increased risk for both
      in-hospital and late mortality (p < 0.05). Valve size did not influence late
      survival or event-free survival regardless of body surface area. CONCLUSIONS: The
      use of small aortic valve prostheses in octogenarians does not adversely affect
      the incidence of early or late mortality or cardiac events.

PMID- 9768919
TI  - Mitral valve replacement: randomized trial of St. Jude and Medtronic Hall
      prostheses.
AB  - BACKGROUND: This study was designed to better define the merits of the bileaflet
      and tilting-disc valves. METHODS: We prospectively randomized 156 patients (mean
      age, 59 years) to receive either the St. Jude (n = 80) or the Medtronic Hall (n =
      76) mitral valve prosthesis between September 1986 and December 1997. The two
      groups were not significantly different with respect to preoperative New York
      Heart Association class, left ventricular ejection fraction, incidence of mitral
      stenosis or insufficiency, extent of coronary artery disease, completeness of
      revascularization, or cross-clamp or bypass time. RESULTS: The operative
      mortality (11.2% versus 13.1%, St. Jude versus Medtronic Hall, respectively) and
      late mortality (27% versus 22%, St. Jude versus Medtronic Hall, respectively)
      were not significantly different. Follow-up was complete in all hospital
      survivors with a mean of 60.7 months (range, 1 to 133 months). The analysis of 10
      year actuarial survival and freedom from valve-related events demonstrated no
      significant differences between the cohorts. Freedom from reoperation was higher
      in the St. Jude group (p < 0.01). Comparisons of patient functional status and
      echocardiographic hemodynamic parameters obtained at the time of follow-up
      demonstrated no significant differences between the two prostheses. CONCLUSIONS:
      This study suggests that there is no difference between the St. Jude and
      Medtronic Hall prostheses with respect to late clinical performance or
      hemodynamic results and therefore does not support the preferential selection of
      either prosthesis.

PMID- 9768920
TI  - Bilateral radial artery grafts in coronary reconstruction: technique and early
      results in 261 patients.
AB  - BACKGROUND: To achieve arterial myocardial revascularization we have
      progressively used more single and bilateral internal thoracic artery and radial
      artery (RA) grafts. We evaluated our early experience with bilateral radial
      artery to coronary grafts. METHODS: As part of their coronary reconstruction, 261
      patients had 522 bilateral RA grafts from March 1995 to June 1997. Mean age was
      61.1 years. There were 70 (27%) patients with non-insulin-dependent diabetes and
      13 (5%) with insulin-dependent diabetes. Unstable angina was seen in 54 (21%)
      patients. Left ventricular ejection fraction less than 50% was noted in 74
      (28.4%) patients. Coronary revascularization was completed with additional single
      internal thoracic artery in 229 patients (88%), bilateral internal thoracic
      artery in 25 patients (9.6%), and vein grafts in 13 patients (5%). Intraluminal
      1% papaverine in blood was used. There were 3.6 +/- 0.7 distal anastomoses per
      patient, with a total of 939, 921 (98%) with arterial conduits and 18 with vein
      grafts. Five hundred ninety-four (63%) of the anastomoses were with RAs. Of the
      522 RA grafts 72 (13.8%) were used sequentially. The RA was most frequently
      placed to the circumflex marginals (261 patients, 100%) and posterior descending
      (169 patients, 65%). Proximal RA anastomosis was directly to the aorta in 472
      patients, the internal thoracic artery in 42, or another RA in 8. All anastomoses
      were constructed during a single cross-clamp period (mean, 74.2 +/- 26.6
      minutes). RESULTS: Operative mortality was 2 patients (0.8%). Complications
      included stroke in 2 patients (0.8%), deep internal infection in 2 (0.8%),
      reoperation for hemorrhage in 1 (0.4%), and myocardial infarction in 2 (0.8%).
      Mean peak creatine kinase-MB was 13.2 +/- 11.6 IU/L. There were no forearm
      infections or hand ischemia, but there were 4 (1.6%) hematomas, 1 requiring
      drainage. Angiography was done on 16 patients with RA grafts, a mean of 4.2
      months postoperatively. Twenty of 22 distal anastomoses were patent (91%), and
      there was 1 occlusion and 1 string sign. CONCLUSIONS: Bilateral RA to coronary
      grafting extends the scope of arterial myocardial revascularization, and is safe.
      Late angiographic results are required.

PMID- 9768921
TI  - Left ventricular functional improvement after transmyocardial laser
      revascularization.
AB  - BACKGROUND: Transmyocardial laser revascularization has been used to treat
      patients with end-stage coronary artery disease that is not amenable to standard
      revascularization. Although there is evidence of angina relief and quality of
      life enhancement, there is little information concerning improvement in
      myocardial contractility. The purpose of this study was to determine whether
      transmyocardial laser revascularization improves myocardial function in
      chronically ischemic myocardium. METHODS: In a model of chronic ischemia by
      Ameroid occlusion of the circumflex artery, domestic pigs (n = 8) were treated
      with transmyocardial laser revascularization. Before laser treatment, segmental
      contraction was assessed at rest and with dobutamine stress echocardiography.
      Myocardium subtended by the occlusion was compared with that remote from the
      occlusion. Six weeks after transmyocardial laser revascularization, the animals
      were restudied at rest and with stress, and then sacrificed. Sham-treated control
      animals (n = 4) underwent the same procedures but were not treated with
      transmyocardial laser revascularization. Control animals did not demonstrate
      significant recovery of function. RESULTS: Transmyocardial laser
      revascularization improved resting function in chronically ischemic myocardium by
      100%. CONCLUSIONS: Transmyocardial laser revascularization significantly improves
      the function of chronically ischemic myocardium. These data may help explain the
      mechanisms by which transmyocardial laser revascularization is clinically
      effective.

PMID- 9768922
TI  - Preconditioning during simulated MIDCABG attenuates blood flow defects and
      neutrophil accumulation.
AB  - BACKGROUND: Ischemic preconditioning (IP) may be cardioprotective in minimally
      invasive direct coronary artery bypass where cardioplegia is not used. This study
      tested the hypothesis that IP of the area at risk (AAR) would attenuate
      postischemic injury from transient coronary artery occlusion. METHODS: In 19
      anesthetized dogs, the left anterior descending coronary artery was occluded for
      30 minutes (simulating coronary occlusion during anastomosis) followed by 3 hours
      of reperfusion. In 10 dogs, occlusion was preceded by 5 minutes of occlusion and
      5 minutes of reperfusion (IP), whereas 9 other dogs had no IP (control, C).
      RESULTS: Thirty minutes of left anterior descending occlusion caused comparable
      dyskinesis (systolic shortening, sonomicrometry) in the AAR in C (baseline, 29%
      +/- 3% to 3% +/- 2%) and in IP (baseline, 29% +/- 2% to -0.3% +/- 2%). After 3
      hours of reperfusion, systolic shortening was significantly depressed in C (20%
      +/- 4%), and was not significantly improved by IP (24% +/- 3%, p = 0.8 versus C).
      Postischemic diastolic stiffness in the AAR was not altered by IP versus C (0.60
      +/- 0.12 versus 0.41 +/- 0.13). Plasma creatine kinase activity was similar
      between C and IP at the end of reperfusion (20 +/- 11 versus 16 +/- 5 U/g).
      Postischemic AAR blood flow (in milliliters per minute per gram of tissue) at 180
      minutes of reperfusion decreased by 56% versus baseline in C (from 1.04 +/- 0.4
      to 0.46 +/- 0.12; p < 0.05) compared with no change in IP (from 0.74 +/- 0.23 to
      0.60 +/- 0.10), but there was no significant group difference at this time.
      Myeloperoxidase activity as an index of neutrophil accumulation in AAR was
      decreased in IP versus C (0.4 +/- 0.09 versus 0.7 +/- 0.04 U/microg tissue).
      CONCLUSIONS: Ischemic preconditioning does not decrease postischemic wall motion
      and only modestly increases postischemic blood flow abnormalities in the AAR, but
      does significantly inhibit neutrophil accumulation.

PMID- 9768923
TI  - Inhibition of inducible nitric oxide synthase after myocardial ischemia increases
      coronary flow.
AB  - BACKGROUND: The role of nitric oxide synthase in myocardial ischemia-reperfusion
      injury is complex. Our hypothesis was that inducible nitric oxide synthase has a
      role in the regulation of coronary flow after ischemia. METHODS: Four groups of
      isolated blood-perfused rabbit hearts underwent sequential periods of perfusion,
      ischemia, and reperfusion (20, 30, and 20 minutes). Two groups underwent 40
      minutes of perfusion. Ischemic groups received saline vehicle, N omega-nitro-L
      arginine methyl ester (L-NAME) or the highly specific inducible nitric oxide
      synthase inhibitor 1400W in low or high doses during reperfusion. Two nonischemic
      groups were treated with saline vehicle or 1400W during the last 20 minutes of
      perfusion. Left ventricular developed pressure and coronary flow were measured
      after each perfusion period. Ventricular levels of myeloperoxidase and cyclic
      guanosine monophosphate were measured at the end of the second perfusion period.
      RESULTS: Coronary flow was significantly increased in both 1400W groups versus L
      NAME (p < 0.001) and in high-dose 1400W versus control (p < 0.001). Coronary flow
      was not significantly different between the nonischemic groups. Left ventricular
      developed pressure was not significantly different among the ischemic groups or
      between the two nonischemic groups. There were no differences in cyclic guanosine
      monophosphate levels in any of the ischemic hearts. Myeloperoxidase levels were
      significantly elevated in L-NAME versus high-dose 1400W, nonischemic 1400W, and
      nonischemic saline groups (p < 0.02). CONCLUSIONS: Highly selective inhibition of
      inducible nitric oxide synthase results in increased coronary flow after ischemia
      but not after continuous perfusion. This occurs with decreased neutrophil
      accumulation and a trend toward increased contractility without elevation of
      cyclic guanosine monophosphate levels.

PMID- 9768924
TI  - Preoperative predictors of cost in Medicare-age patients undergoing coronary
      artery bypass grafting.
AB  - BACKGROUND: Identification of preoperative factors that contribute to the cost of
      coronary artery bypass grafting could aid in predicting the procedure's expense.
      In this study, 30 sociodemographic and clinical preoperative factors were
      examined with "survival analysis" techniques to determine characteristics related
      to total hospital cost. METHODS: Characteristics of all patients age 65 or older
      undergoing isolated coronary artery bypass grafting from July 1993 to April 1995
      (n = 757) were recorded. Software was developed within the hospital's Transitions
      Systems, Inc, database to calculate the outcome variable of total cost.
      Nonparametric methods were used for the univariate analysis of the data, and the
      Cox proportional hazards model was used for the multivariable analysis, censoring
      25 patients who died in the hospital. RESULTS: Median hospital cost from the day
      of the operation until discharge was $15,198. Median length of stay after the
      operation was 6 days. Multivariable analysis revealed that age, preoperative
      renal failure, history of cerebrovascular accident, low ejection fraction, and
      surgical urgency were independent predictors of total cost. CONCLUSIONS: This
      study, using an accurate representation of true hospital cost and a modeling
      technique that accounts for the confounding effect of in-hospital death on cost,
      provides a template for analysis of cost in other patient groups.

PMID- 9768925
TI  - Modifying risk for extracorporeal circulation: trial of four antiinflammatory
      strategies.
AB  - BACKGROUND: Despite recent rediscovery of beating heart cardiac surgical
      techniques, extracorporeal circulation remains appropriate for most heart
      operations. To minimize deleterious effects of cardiopulmonary bypass,
      antiinflammatory strategies have evolved. METHODS: Four state-of-the-art
      strategies were studied in a prospective, randomized, preoperatively risk
      stratified, 400-patient study comprising primary (n = 358), reoperative (n = 42),
      coronary (n = 307), valve (n = 27), ascending aortic (n = 9), and combined
      operations (n = 23). Groups were as follows: standard, roller pump, membrane
      oxygenator, methylprednisolone (n = 112); aprotinin, standard plus aprotinin (n =
      109); leukocyte depletion, standard plus a leukocyte filtration strategy (n =
      112); and heparin-bonded circuitry, centrifugal pumping with surface modification
      (n = 67). RESULTS: Analysis of variance, linear and logistic regression, and
      Pearson correlation were applied. Actual mortality (2.3%) was less than half the
      risk stratification predicted mortality (5.7%). The treatment strategies
      effectively attenuated markers of the inflammatory response to extracorporeal
      circulation. Compared with the other groups the heparin-bonded circuit had highly
      significantly decreased complement activation (p = 0.00001), leukocyte filtration
      blunted postpump leukocytosis (p = 0.043), and the aprotinin group had less
      fibrinolysis (p = 0.011). Primary end points, length of stay, and hospital
      charges, were positively correlated with operation type, age, pump time, body
      surface area, stroke, pulmonary sequelae, predicted risk for stroke, predicted
      risk for mortality, and risk strata/treatment group interaction (p = 0.0001). In
      low-risk patients, leukocyte filtration reduced length of stay by 1 day (p =
      0.02) and mean charges by $2,000 to $6,000 (p = 0.05). For high-risk patients,
      aprotinin reduced mean length of stay up to 10 fewer days (p = 0.02) and mean
      charges by $6,000 to $48,000 (p = 0.0007). CONCLUSIONS: These pharmacologic and
      mechanical strategies significantly attenuated the inflammatory response to
      extracorporeal circulation. This translated variably into improved patient
      outcomes. The increased cost of treatment was offset for selected strategies
      through the added value of significantly reduced risk.

PMID- 9768926
TI  - Myocardial protection during antegrade versus retrograde cardioplegia.
AB  - BACKGROUND: It has been suggested that the right ventricular myocardium is
      suboptimally protected during retrograde blood cardioplegia. METHODS: Twenty
      patients undergoing an elective coronary bypass procedure were randomized to
      receive antegrade or retrograde mild hypothermic blood cardioplegia.
      Transventricular differences in oxygen extraction, lactate production, and pH
      were monitored during aortic cross-clamping, and myocardial biopsy specimens were
      taken from both ventricles before cannulation and 15 minutes after aortic
      declamping for analysis of adenine nucleotides and their breakdown products. The
      extent of myocardial injury was estimated by monitoring postoperative leakage of
      troponin T and the MB isoenzyme of creatine kinase. Hemodynamic recovery and
      postoperative complications were noted. RESULTS: The preoperative characteristics
      of the two groups were similar. Oxygen extraction and lactate production in the
      right ventricular myocardium were higher in the retrograde group. In this group,
      the right ventricle also extracted more oxygen and produced more lactate and acid
      than did the left ventricle. Tissue levels of adenine nucleotides tended to
      decrease in both ventricles during operation, with no differences between them.
      The level of adenosine catabolites did increase somewhat in the right ventricular
      myocardium of the retrograde cardioplegia group after aortic declamping. There
      was a tendency for more prominent efflux of troponin T and the MB isoenzyme of
      creatine kinase in the retrograde group. Nevertheless, the postoperative course
      was uneventful in both groups. CONCLUSIONS: Retrograde mild hypothermic blood
      cardioplegia leads to metabolic changes compatible with right ventricular
      ischemia. Nevertheless, tissue levels of high-energy phosphates are well
      preserved, and the postoperative course seems to be unproblematic. Care should be
      taken when retrograde normothermic blood cardioplegia is provided for patients
      with right ventricular hypertrophy, poor right ventricular function, or severe
      preoperative myocardial ischemia.

PMID- 9768927
TI  - Mitral valve replacement with the St. Jude Medical prosthesis: a 15-year follow
      up.
AB  - BACKGROUND: A retrospective study was conducted to analyze the results of St.
      Jude Medical mitral valve replacement. METHODS: From January 1979 to December
      1989, 870 patients (54% women, 46% men; mean age, 55.8 +/- 6.2 years) underwent
      mitral valve replacement with the St. Jude Medical prosthesis. Of these
      operations 616 were isolated mitral valve replacements and 254 were double valve
      replacements. Coronary artery bypass grafting was performed concomitantly in 55
      patients (6.3%). RESULTS: Overall, early mortality was 5.05%, with 4.2% for the
      isolated mitral valve procedure and 7.08% for the double valve replacement.
      Follow-up at 15 years was complete in 859 patients (98.74%). Mean follow-up time
      was 93.5 months, for a total of 6,436 years. Actuarial survival at 15 years was
      59.5% +/- 5%, 60.5% +/- 6%, and 56.9% +/- 9%, for the entire group, the isolated
      mitral valve and double valve procedures, respectively. Multivariate analysis
      identified age, sex, hospital stay, and preoperative mitral regurgitation as
      independent prognosis factors for overall mortality. Of 606 patients alive at the
      latest follow-up, the New York Heart Association class improved significantly
      (from 67% class III/IV before the operation to 88% class I/II after the
      operation). All patients received warfarin to maintain an international
      normalized ratio between 3.5 and 4. The linearized rates (% per patient-year) of
      thrombosis, thromboembolism, and major hemorrhage were, respectively, 0.21, 0.75,
      and 0.94 for the entire group; 0.18, 0.67, and 0.88 for the isolated mitral valve
      operation; and 0.15, 0.92, and 1.08 for the double valve replacement. For the
      entire group the freedom from thrombosis and thromboembolism at 15 years was
      98.1% +/- 1% and 88% +/- 4%, respectively. No case of structural dysfunction
      occurred. The freedom from paravalvular leak and endocarditis at 15 years was
      95.3% +/- 2% and 97.3% +/- 2.4%, respectively. The probability of remaining free
      from reoperation at 15 years was therefore 95.6% +/- 2.5%. CONCLUSIONS: These
      results confirm that the St. Jude Medical valve is a reliable prosthesis with
      very low thrombosis and thromboembolism rates, allowing the use of a low dose of
      anticoagulation with an international normalized ratio of about 3.

PMID- 9768928
TI  - The adenosine-triphosphate-sensitive potassium-channel opener pinacidil is
      effective in blood cardioplegia.
AB  - BACKGROUND: This study was designed to evaluate the adenosine-triphosphate
      sensitive potassium channel opener pinacidil as a blood cardioplegic agent.
      METHODS: Using a blood-perfused, parabiotic, Langendorff rabbit model, hearts
      underwent 30 minutes of normothermic ischemia protected with blood cardioplegia
      (St. Thomas' solution [n = 8] or Krebs-Henseleit solution with pinacidil [50
      micromol/L, n = 81) and 30 minutes of reperfusion. Percent recovery of developed
      pressure, mechanical arrest, electrical arrest, reperfusion ventricular
      fibrillation, percent tissue water, and myocardial oxygen consumption were
      compared. RESULTS: The percent recovery of developed pressure was not different
      between the groups (52.3 +/- 5.9 and 52.8 +/- 6.9 for hyperkalemic and pinacidil
      cardioplegia, respectively). Pinacidil cardioplegia was associated with prolonged
      electrical and mechanical activity (14.4 +/- 8.7 and 6.1 +/- 3.9 minutes),
      compared with hyperkalemic cardioplegia (1.1 +/- 0.6 and 1.1 +/- 0.6 minutes,
      respectively; p < 0.05). Pinacidil cardioplegia was associated with a higher
      reperfusion myocardial oxygen consumption (0.6 +/- 0.1 versus 0.2 +/- 0.0 mL/100
      g myocardium/beat; p < 0.05) and a higher percent of tissue water (79.6% +/- 0.7%
      versus 78.6% +/- 1.2%; p < 0.05). CONCLUSIONS: Systolic recovery was not
      different between groups, demonstrating comparable effectiveness of pinacidil and
      hyperkalemic warm blood cardioplegia.

PMID- 9768929
TI  - Operation for chronic traumatic aortic aneurysm: when and how?
AB  - BACKGROUND: There are few guidelines for surgical intervention late after
      unoperated traumatic aortic rupture. We reviewed our experience and the
      literature to determine when and how to operate. METHODS: Between 1987 and 1997,
      we treated 9 patients aged 22 to 82 years with chronic traumatic aneurysm. Seven
      patients underwent aneurysm resection. Two patients have not been operated on.
      The injury-to-operation interval ranged from 8 weeks to 18 years (mean, 4.1
      years). One patient underwent median sternotomy and patch repair during
      hypothermic circulatory arrest. Six patients underwent left thoracotomy: 2 were
      operated on with left atrio-femoral bypass, and 4 with hypothermic circulatory
      arrest and ascending aortic cannulation. RESULTS: There was no surgical mortality
      or morbidity. The 2 patients who were not operated on remained asymptomatic
      without radiologic change in the aneurysm after follow-up of 2 and 9 years.
      CONCLUSIONS: From this limited experience and literature review, we make the
      following subjective observations: (1) all patients with new symptoms should be
      operated on promptly, and (2) asymptomatic densely calcified aneurysms detected
      more than 2 years after the accident can be observed by repeated tomography
      unless new symptoms arise.

PMID- 9768930
TI  - Early and late risk factors in surgical treatment of acute type A aortic
      dissection.
AB  - BACKGROUND: Morbidity and mortality of emergency repair of type A dissecting
      aneurysms of the aorta are high. This is an attempt to investigate the risk
      determinants of early and late results. METHODS: A series of preoperative and
      operative variables were retrospectively collected from the clinical records of
      291 patients operated on between January 1, 1979, and December 31, 1995. Risk
      factors for surgical death were investigated with univariate analysis and
      stepwise logistic regression. Follow-up was conducted between December 1995 and
      February 1996. Analysis of late results was conducted by means of actuarial
      survival curves (life method). After removing the surgical deaths, risk factors
      for late deaths were analyzed by a Cox model. RESULTS: The in-hospital mortality
      rate was 36.1%. Significant independent determinants of operative or early death
      were preoperative shock, preoperative neurologic impairment, operation before
      1986, perioperative bleeding, and prolonged clamping time. The 10-year survival
      rate was 36.9% +/- 4.4%. Twenty-six patients required repeat operation. The long
      term prognosis was significantly worse in patients who needed reoperation.
      CONCLUSIONS: Growing awareness of this disease and quicker diagnosis have
      increased the number of patients with acute dissection of the ascending aorta who
      are taken early to operation. This new challenge must be met by better
      preoperative support and intraoperative monitoring, and by surgical techniques
      that focus on lowering the rate of late complications, for which lifelong follow
      up must be provided.

PMID- 9768931
TI  - A dual-vent left heart deairing technique markedly reduces carotid artery
      microemboli.
AB  - BACKGROUND: Cerebral embolization, mainly bubbles, follows aortic declamping in
      left heart valve operations. Embolization is not prevented by conventional left
      heart deairing methods. We have validated a "dual-vent" deairing technique, which
      uses high-flow left ventricular and aortic venting from the working heart into
      the cardiopulmonary bypass venous line before aortic declamping. METHODS: After
      left heart valve replacement, intraoperative color-flow Doppler echocardiography
      was used to monitor the right common carotid embolic activity in 58 consecutive
      patients who underwent conventional deairing (group 1), 14 consecutive patients
      who underwent deairing by the dual-vent technique (group 2), and 4 patients who
      received nonvented coronary artery bypass grafting who did not require deairing
      (group 3). RESULTS: The median emboli count recorded after aortic declamping was
      1,647 (range, 342 to 6,852) and 101 (range, 0 to 865) in the group 1 and 2
      patients, respectively (p < 0.0001). The efficacy of the dual-vent technique
      improved throughout the series: in the last 7 patients, the emboli counts often
      approached the very low levels seen in group 3 patients (median, 8; range, 1 to
      16). CONCLUSIONS: Cerebral embolization after aortic declamping in left heart
      valve operations was significantly reduced by this dual-vent deairing technique.

PMID- 9768932
TI  - Fibrinolysis-adjusted perioperative low-dose aprotinin reduces blood loss in
      bypass operations.
AB  - BACKGROUND: Postoperative bleeding still remains a serious problem in bypass
      surgery. This study evaluated fibrinolysis and perioperative low-dose
      antifibrinolytic regimens adjusted to the time course of fibrinolysis. METHODS:
      In a prospective, randomized study of 42 patients undergoing bypass grafting,
      patients received low-dose aprotinin (group A; n = 14) or low-dose tranexamic
      acid (group TA; n = 14) intraoperatively and postoperatively, respectively, with
      no antifibrinolytics for comparison (group C; n = 14). Parameters of
      procoagulation, fibrinolysis, and activated factor VII were measured
      preoperatively, intraoperatively, and postoperatively. Blood loss was determined
      up to 24 hours. RESULTS: The level of thrombin-antithrombin III complex was
      significantly decreased postoperatively in the treatment groups (group A and TA
      versus C: 25 +/- 14 and 19 +/- 10 microg/L, respectively, versus 40 +/- 21
      microg/L; p < 0.05). Levels of plasmin-antiplasmin complexes were significantly
      decreased postoperatively in group A (607 +/- 231 microg/L) versus group C (825
      +/- 225 microg/L) (p < 0.05) but were increased in group TA (1,145 +/- 394
      microg/L) versus group C (p < 0.05). At all times intraoperatively and
      postoperatively, levels of D-dimers were significantly decreased in group A and
      group TA versus control (p < 0.001), indicating that fibrinolysis persists after
      the operation. Intraoperatively, the factor VIIa level decreased significantly in
      group A (20 +/- 8 mU/mL) versus group C (31 +/- 15 mU/mL) (p < 0.05), but not in
      group TA (32 +/- 15 mU/mL). Blood loss was significantly lower in group A (135 +/
      37 mL) and group TA (155 +/- 71 mL) versus group C (354 +/- 170 mL) (p < 0.001).
      CONCLUSIONS: This low-dose aprotinin regimen adjusted to perioperative
      fibrinolysis reduces blood loss significantly in coronary bypass grafting. For
      further progress in this subject, clinical investigations of individual
      fibrinolysis-adjusted antifibrinolytic treatment seems warranted.

PMID- 9768933
TI  - Operative results after the Cox/maze procedure combined with a mitral valve
      operation.
AB  - BACKGROUND: There have been few reports on postoperative morbidity and mortality
      analyses after concomitant mitral valve operation and the Cox/maze procedure.
      METHODS: Between April 1993 and August 1995, 87 consecutive patients with chronic
      atrial fibrillation underwent a mitral valve operation and concomitant Cox/maze
      procedure at Iwate Medical University. The patients were divided into the
      replacement group (n = 31) and repair group (n = 56) according to the method of
      mitral valve replacement. Our initial experience with the combined operative
      procedures is presented along with the operative mortality and morbidity rates.
      Univariate analysis on preoperative and intraoperative variables affecting early
      mortality and morbidity is carried out retrospectively. RESULTS: Total
      cardiopulmonary bypass time in all patients was 177.2 +/- 70.1 minutes. Total
      aortic cross-clamp time was 121.7 +/- 30.8 minutes. Total intensive care unit
      stay was 5.3 +/- 7.9 days. The average intubation period was 55.5 +/- 187.6
      hours. The intensive care unit stay and the intubation period of the replacement
      group were longer than those of the repair group. There were four operative
      deaths among the 87 patients (4.6%). All repair group patients survived
      operation, whereas 4 replacement group patients died after operation. In all
      patients, the New York Heart Association functional class was higher (p = 0.028)
      in those who died than in those who survived. The overall restoration rate from
      atrial fibrillation was 79.5% (66 of 83 survivors). Seventeen patients (20.5%)
      had persistent atrial fibrillation postoperatively. Sick sinus syndrome occurred
      in 7 patients (8.4%). In the repair group, the restoration rate was 76.8%,
      whereas in the replacement group it was 85.2% for the survivors. CONCLUSIONS: The
      Cox/maze procedure can be combined with a mitral valve operation with acceptably
      low operative risk. Analysis of risk factors of early mortality revealed that the
      type of mitral valve operation (replacement versus repair) and higher
      preoperative New York Heart Association functional class were associated with
      mortality. Long-term results from this combined procedure should be clearly
      demonstrated before its universal acceptance.

PMID- 9768934
TI  - Fifth-year hemodynamic performance of the prima stentless aortic valve.
AB  - BACKGROUND: The medium-term hemodynamic performance of stentless valves has not
      been widely reported, particularly in comparison with in vitro studies.
      Therefore, we have assessed prospectively the hemodynamics of the Edwards Prima
      valve in its fifth year after implantation in the aortic position, and compared
      the results with those at 1 month after implantation and also with in vitro data.
      METHODS: Thirty-five patients (age, 77 +/- 6 years; 19 men) were prospectively
      studied by Doppler echocardiography at 1 month and 52 +/- 8 months after
      implantation of a Prima stentless valve. Valve hemodynamics were assessed by
      measuring the mean pressure gradient, mean valve resistance, and effective
      orifice area. Left ventricular systolic function was quantified by ejection
      fraction, the degree of hypertrophy by ventricular mass index, and the ratio of
      ventricular wall thickness to cavity radius as a measure of ventricular geometry.
      RESULTS: With a mean valve size of 24.6 +/- 2.2 mm in the fifth year after
      implantation, the mean pressure gradient was 6.2 +/- 3.5 mm Hg, the mean valve
      resistance, 29 +/- 16 dyne x s(-1) x cm(-5)), and the effective orifice area was
      2.05 +/- 0.50 cm2. Compared with 1 month after operation, there was a 47%
      decrease in mean valve resistance (p = 0.002) and a 39% increase in effective
      orifice area (p = 0.001). Furthermore, both effective orifice area and mean valve
      resistance in the fifth year did not differ from their in vitro counterparts,
      whereas the left ventricular ejection fraction (0.64 +/- 0.14), the left
      ventricular mass index (119 +/- 49 g/m2), and the ratio of ventricular wall
      thickness to cavity radius (0.44 +/- 0.13) were within the normal range.
      CONCLUSIONS: This study suggests that the Prima valve is a reliable stentless
      aortic bioprosthesis. This is supported by a favorable medium-term clinical
      outcome, durable hemodynamic performance, and normal mean values of left
      ventricular ejection fraction and mass index in the fifth year after
      implantation.

PMID- 9768935
TI  - Surgical experience with intracardiac myxomas: long-term follow-up.
AB  - BACKGROUND: Myxomas are the most common benign intracardiac tumors. This report
      summarizes our 20-year experience with these tumors. METHODS: Sixty-six patients
      (25 male) with a median age of 39 years (range, 6 to 70 years) underwent surgical
      excision of primary or recurrent intracardiac myxomas during the years 1976 to
      1996. Symptom duration ranged from 2 to 8 months. There were 55 left atrial
      myxomas, 10 right atrial myxomas, and 1 biatrial myxoma. Three of the patients
      were in one family. The surgical approach comprised complete wide excision.
      RESULTS: There were two early deaths. Late follow-up is 89% (57/64) complete.
      There was one late death, which was not due to a cardiac cause. Echocardiography
      at a mean follow-up of 66.9 months (range, 7 to 241 months) showed no recurrence
      of sporadic myxomas. However, 2 of the 3 patients with familial myxomas had
      recurrence. CONCLUSIONS: Surgical excision of atrial myxoma gives excellent short
      term and long-term results leading to eventual cure of nonfamilial myxomas.
      However, familial myxomas retain a strong tendency to recur even 20 years after
      excision.

PMID- 9768936
TI  - Gene transfer to vein graft wall by HVJ-liposome method: time course and
      localization of gene expression.
AB  - BACKGROUND: A novel gene transfer method using liposomes with a viral envelope of
      hemagglutinating virus of Japan (HVJ) has been reported to be very effective for
      gene transfection into somatic cells and might be applicable to improve the
      patency of vein grafts. The present study examined the time course and
      localization of gene expression to assess the feasibility of ex vivo gene
      transfer into the vein graft by the HVJ-liposome method. METHODS: The HVJ
      liposome complex containing either beta-galactosidase plasmid DNA
      (deoxyribonucleic acid) or no genes (controls) (experiment 1) or fluorescein
      isothiocyanate-labeled oligonucleotides either with or without HVJ-liposomes
      (experiment 2) was infused into rabbit vein grafts and allowed to incubate before
      autologous transplantation to carotid arteries. RESULTS: In experiment 1, all
      grafts incubated with beta-galactosidase plasmid with HVJ-liposomes showed the
      blue staining of X-gal 7 days after operation, whereas the controls did not. The
      blue granules were present in the medial and adventitial tissue and were still
      present after 14 days. In experiment 2, many fluorescein isothiocyanate-labeled
      nuclei were observed in the graft wall 2 and 4 days after operation and remained
      present mainly in the media of HVJ-liposome-treated grafts after 7 and 14 days,
      when no fluorescein isothiocyanate activity was observed without HVJ-liposome
      treatment. CONCLUSIONS: These results demonstrated the feasibility of ex vivo
      transfection to the medial and adventitial tissue of the vein graft by the HVJ
      liposome method and suggest the possibility of its clinical application to
      prevent vein graft failure.

PMID- 9768937
TI  - Effect of modified ultrafiltration in high-risk patients undergoing operations
      for congenital heart disease.
AB  - BACKGROUND: Modified ultrafiltration (MUF) after cardiopulmonary bypass (CPB) in
      children decreases body water, removes inflammatory mediators, improves
      hemodynamics, and decreases transfusion requirements. The optimal target
      population for MUF needs to be defined. This prospective, randomized study
      attempted to identify the best candidates for MUF during operations for
      congenital heart disease. METHODS: Informed consent was obtained from 100
      consecutive patients with complex congenital heart disease undergoing operations
      with CPB. They were randomized into a control group (n = 50) of conventional
      ultrafiltration during bypass and an experimental group using dilutional
      ultrafiltration during bypass and venovenous modified ultrafiltration after
      bypass (MUF group, n = 50). Postoperative arterial oxygenation, duration of
      ventilatory support, transfusion requirements, hematocrit, chest tube output, and
      time to chest tube removal were compared between the groups stratified by age and
      weight, CPB technique, existence of preoperative pulmonary hypertension, and
      diagnosis. RESULTS: There were no MUF-related complications. In patients with
      preoperative pulmonary hypertension, MUF significantly improved postoperative
      oxygenation (445 +/- 129 mm Hg versus control: 307 +/- 113 mm Hg, p = 0.002),
      shortened ventilatory support (42.9 +/- 29.5 hours versus control: 162.4 +/-
      131.2 hours, p = 0.0005), decreased blood transfusion (red blood cells: 16.2 +/-
      18.2 mL/kg versus control: 41.4 +/- 27.8 mL/kg, p = 0.01; coagulation factors:
      5.3. +/- 6.9 mL/kg versus control: 32.3 +/- 15.5 mL/kg, p = 0.01), and led to
      earlier chest tube removal. In neonates (< or =30 days), MUF significantly
      reduced transfusion of coagulation factors (5.4 +/- 5.0 mL/kg versus control:
      39.9 +/- 25.8 mL/kg, p = 0.007), and duration of ventilatory support (59.3 +/-
      36.2 hours versus 242.1 +/- 143.1 hours, p = 0.0009). In patients with prolonged
      CPB (>120 minutes), MUF significantly reduced the duration of ventilatory support
      (44.7 +/- 37.0 hours versus 128.7 +/- 133.4 hours, p = 0.002). No significant
      differences were observed between MUF and control patients for any parameter in
      the presence of ventricular septal defect without pulmonary hypertension,
      tetralogy of Fallot, or aortic stenosis. CONCLUSIONS: Modified ultrafiltration
      after CPB is safe and decreases the need for homologous blood transfusion, the
      duration of ventilatory support, and chest tube placement in selected patients
      with complex congenital heart disease. The optimal use of MUF includes patients
      with preoperative pulmonary hypertension, neonates, and patients who require
      prolonged CPB.

PMID- 9768939
TI  - Does banding the pulmonary artery affect pulmonary valve function after the Damus
      Kaye-Stansel operation?
AB  - BACKGROUND: The Damus-Kaye-Stansel (DKS) operation can be an effective palliation
      in patients who have single-ventricle physiology and systemic outflow
      obstruction. Pulmonary artery banding (PAB) may be used as a preliminary
      procedure in these patients to limit overperfusion of the pulmonary circulation.
      In some series, the DKS operation has been associated with pulmonary
      insufficiency (PI). We retrospectively analyzed medical records of our patients
      who had PAB and later DKS to determine the incidence of PI in these patients.
      METHODS: Between 1982 and 1996, 15 patients underwent PAB before DKS. Median age
      at PAB placement was 7 days and median duration of PAB was 7 months.
      Echocardiograms obtained before PAB, before DKS, and at the most recent post-DKS
      follow-up were reviewed. RESULTS: Follow-up ranged from 1 to 15 years (mean
      follow-up, 7.5 years). One patient had trivial PI before PAB, which progressed to
      moderate PI at the last follow-up. Only 1 other patient had mild PI, but only at
      the last follow-up after DKS. CONCLUSIONS: These findings suggest that prior PAB
      does not appear to cause significant PI in patients slated for DKS, and the
      incidence of significant PI after the DKS operation is relatively low.

PMID- 9768938
TI  - Primum atrial septal defect in children: early results, risk factors, and freedom
      from reoperation.
AB  - BACKGROUND: Repair of primum atrial septal defect in children usually is
      associated with a low operative mortality, except for a subgroup of children with
      congestive heart failure. To determine the early mortality and incidence of
      reoperation in children with primum atrial septal defect, we analyzed
      retrospectively the results of patients who underwent repair of this defect.
      METHODS: Between July 1982 and December 1996, 180 children underwent repair of
      primum atrial septal defect. The mean age at repair was 4.6 years (median, 3.6
      years; range, 1 month to 16.4 years); of the 180 children, 23 were infants less
      than 1 year of age. Absent or mild symptoms were present in 145 (80%), whereas 34
      (20%) of children presented with severe symptoms or congestive heart failure.
      RESULTS: Early mortality occurred in 3 (1.6%); 2 were less than 1 year of age.
      Follow-up ranged from 2 months to 14.5 years (mean, 6 +/- 4.2 years). Actuarial
      survival is 98% at 10 years with no late deaths. Age less than 1 year is a
      predictor of death. During follow-up, 17 (9%) of the 180 patients underwent
      reoperation, 5 of whom were in the infant group. Five underwent reoperation for
      subaortic obstruction, and 12 for left atrioventricular valve regurgitation of
      whom 11 were repaired; and 1 required valve replacement. Age and preoperative
      moderate-to-severe left atrioventricular valve regurgitation were predictors of
      reoperation. CONCLUSIONS: Results of the repair of primum atrial septal defect
      during childhood are favorable. Infants have a higher risk for death and
      reoperation. Left atrioventricular valve insufficiency and subaortic stenosis are
      important late complications and can be repaired safely at reoperation.

PMID- 9768940
TI  - Arterial switch in hearts with left ventricular outflow and pulmonary valve
      abnormalities.
AB  - BACKGROUND: Pulmonary valve and left ventricular outflow tract abnormalities
      (LVOT) may not be absolute contraindications to arterial switch operation (ASO).
      METHODS: In this study we analyze long-term outcome for 26 such transposition
      patients (6.3% of our ASO cohort). Median age and weight were 69 days (7 to 3,631
      days) and 4.5 kg (2.6 to 34 kg). Pulmonary valve abnormalities included bicuspid
      valve (n = 4) and dysplastic valve (n = 5). The LVOT abnormalities (n = 17)
      included accessory atrioventricular valve/endocardial cushion tissue,
      fibromuscular ring, anomalous muscle bands, and septal malalignment. Patients
      with dynamic LVOT obstruction were excluded. The median preoperative left
      ventricular to pulmonary artery peak systolic pressure gradient was 30 mm (0 to
      93 mm), or 50 mm (16 to 93 mm) if patients with isolated valve abnormalities are
      excluded. The ASO was performed according to our standard technique with or
      without LVOT resection or pulmonary valvotomy as required. RESULTS: There were
      two perioperative deaths (7.7%; 95% confidence interval, 0.9% to 25%), and no
      late deaths during 1,934 patient-months of follow-up time. Actuarial freedom from
      reoperation for neoaortic valve or LVOT problems is 87% (+/- 7) at 130 months,
      representing two reoperations. One was performed for neoaortic insufficiency plus
      LVOT obstruction, and the other for isolated LVOT obstruction. One patient
      currently has significant neoaortic insufficiency, and median gradient at last
      follow-up is 0 mm Hg (range, 0 to 35 mm Hg). CONCLUSIONS: The ASO can be
      performed in selected patients with transposition of the great arteries and with
      LVOT abnormalities with early and late survival and functional status similar to
      that of matched patients with normal pulmonary valves and LVOT (p > 0.05), but
      with a greater hazard for reoperation (p < 0.05). Selection for ASO should be
      based on anatomic criteria rather than left ventricular to pulmonary artery
      gradient alone, to avoid assigning these patients with transposition of the great
      arteries to treatment strategies less satisfactory than ASO.

PMID- 9768941
TI  - Homograft replacement of mitral valve in children.
AB  - BACKGROUND: Recent reports have demonstrated successful early outcomes using
      mitral valve homografts in adults. We report our early results after homograft
      mitral valve replacement in 4 children with previous atrioventricular septal
      defects, previous placement of a prosthetic valve, and rheumatic valvular
      disease. METHODS: Between May 1996 and June 1997, 4 children (ages 5, 11, 13, and
      15 years) underwent mitral valve replacement with cryopreserved mitral valve
      homografts at our institution. Preoperative echocardiography confirmed moderately
      severe to severe mitral regurgitation, stenosis, or both in all 4 patients.
      RESULTS: Successful homograft valve replacement was achieved in all 4 patients.
      Based on symptoms, physical examinations, and echocardiographic follow-up, all
      four homograft mitral valves are functioning well with normal hemodynamics. None
      of these patients are receiving warfarin. Follow-up has been limited to 10
      months. CONCLUSIONS: In children requiring mitral valve replacement, the use of
      mitral valve homografts offers advantages over prosthetic valves, such as the
      avoidance of complications associated with thrombosis and anticoagulation.
      Homograft mitral valve replacement is technically feasible in children with
      congenital and rheumatic heart disease and previous prosthetic valves.

PMID- 9768942
TI  - Video-assisted thoracoscopic ligation of patent ductus arteriosus: safe and
      outpatient.
AB  - BACKGROUND: Minimally invasive techniques for interruption of patent ductus
      arteriosus have been reported, but are in use at only a few centers. We examined
      our series of patients who underwent thoracoscopic patent ductus arteriosus
      ligation. METHODS: We reviewed 59 consecutive patients, age 6 days to 50 years,
      weighing 640 g to 62 kg, who underwent video-assisted placement of a stainless
      steel clip across the patent ductus arteriosus. RESULTS: Thirty-eight nonneonates
      and 21 neonates (18 were < or =1,500 g) underwent video-assisted thoracic surgery
      for patent ductus arteriosus closure with intraoperative echocardiographic
      confirmation in nonneonates. There were no residual shunts, transfusions,
      chylothoraces, or significant pneumothoraces. Four were converted to thoracotomy,
      3 for anatomic variances, and 1 for coagulopathy. Thirty-six of 38 nonneonate
      patients stayed less than 24 hours; 18 were discharged the evening of the
      operation. Two were admitted, one after thoracotomy, and one for a small mucosal
      intubation injury. No others required a chest tube. There were two recurrent
      nerve injuries. All neonates survived, and were extubated. CONCLUSIONS: Video
      assisted thoracoscopic ductus closure is a safe, reliable technique and can be
      performed as an outpatient procedure in nonneonate patients.

PMID- 9768943
TI  - Validation of relative value scale for congenital heart operations.
AB  - BACKGROUND: To determine the validity of the newly assigned work relative value
      unit (RVU) scale for surgical procedures for congenital heart disease, we
      measured its relationship to length of hospital stay, total hospital charges, and
      mortality. METHODS: We identified cases by the presence of ICD-9-CM codes in nine
      statewide, administrative hospital discharge abstract databases for 1992.
      Computer algorithms were generated to assign RVUs to individual cases. Spearman
      correlation coefficients between work and practice expense RVUs and median length
      of hospital stay, total hospital charges, and in-hospital mortality were
      determined, as well as parameter estimates from linear and logistic regression.
      RESULTS: Using data from 5,192 cases involving 34 surgical procedures for
      congenital heart disease, higher work RVUs were associated with longer lengths of
      hospital stay (rs = 0.72, p < 0.0001), higher total hospital charges (rs = 0.81,
      p < 0.0001), and higher in-hospital mortality (rs = 0.45, p = 0.01). A 5-point
      increase in the relative value scale was associated with an increase in the
      length of stay by a multiplicative factor of 1.3 (p < 0.0001); total hospital
      charges by 1.5 (p < 0.0001); and the odds of in-hospital death by 1.9 (p <
      0.0001). Findings were similar for practice expense RVUs, as work and practice
      expense RVUs were highly correlated (rs = 0.93, p < 0.0001). CONCLUSIONS: The
      group of work RVUs for surgical procedures for congenital heart defects are
      reasonable relative measures, on average, of physician work for these procedures,
      thus supporting the use of this scale to determine physician reimbursement.
      Practice expense RVUs may not be an independent measure for these procedures.

PMID- 9768944
TI  - Association between age and blood loss in children undergoing open heart
      operations.
AB  - BACKGROUND: Although recent studies indicated young children are at risk for
      increased perioperative hemorrhage after open heart operations, the associations
      between patient age, blood loss and blood product transfusions have not been
      fully defined in children. METHODS: Perioperative blood loss and blood product
      transfusion data were recorded for 414 consecutive children undergoing open heart
      procedures. The children were in the following age groups: 1 month or younger,
      group 1; older than 1 month to 12 months, group 2; older than 1 year to 5 years,
      group 3; and older than 5 years, group 4. RESULTS: Postoperative blood loss and
      blood product transfusions were inversely related to age and differed
      significantly between the four age groups. Multiple preoperative and
      intraoperative factors that possibly influence hemostasis also differed
      significantly between age groups. Median units transfused within 72 hours
      differed significantly with age (p < 0.0001): group 1, 8 units (range, 1 to 19
      units); group 2, 6 units (range, 0 to 21 units); group 3, 2 units (range, 0 to 23
      units); and group 4, 0 units (range, 0 to 38 units). CONCLUSIONS: Blood loss and
      transfusions vary inversely with age. Per kilogram of body weight, neonates bled
      more and received more donor products than any other age group.

PMID- 9768945
TI  - Controlled reperfusion prevents pulmonary injury after 24 hours of lung
      preservation.
AB  - BACKGROUND: Posttransplantation lung reperfusion injury continues to be a major
      problem. We have shown that controlling the initial period of reperfusion limits
      this injury after 2 hours of warm lung ischemia. The effectiveness of this
      modality, however, is unknown after longer periods of cold ischemia, which more
      closely mimics the clinical situation. METHODS: After baseline measurements, 10
      pigs had the left lung flushed with a modified Euro-Collins solution, explanted,
      stored at 4 degrees C for 24 hours, and transplanted into 10 other pigs. Five
      (group 1) underwent uncontrolled reperfusion created by removal of the vascular
      clamps after implantation of the new left lung, mimicking the clinical situation.
      The other five (group 2) underwent controlled reperfusion, which we performed by
      taking blood from the femoral artery, mixing it with a crystalloid solution
      (using a mixer heater) to make the blood hyperosmolar, alkalotic, and substrate
      enriched, and pumping it through a leukocyte-depleting filter into the
      transplanted lung for 10 minutes at a pressure of 20 to 30 mm Hg before removing
      the pulmonary artery clamp. The right pulmonary artery and bronchus were then
      ligated, and left lung function was assessed each hour for 4 hours and compared
      with baseline. RESULTS: Controlled reperfusion (group 2) minimized the
      reperfusion injury, preserving posttransplant pulmonary compliance (92% +/- 1%
      versus 68% +/- 1%; p < 0.001), reducing the rise in pulmonary vascular resistance
      (27% +/- 2% versus 166% +/- 3%; p < 0.001), improving oxygenation (PO2, 425 +/-
      14 versus 82 +/- 11 mm Hg; p < 0.001), and lowering myeloperoxidase activity
      (0.22 +/- 0.02 versus 0.45 +/- 0.02 deltaOD/mg protein per minute; p < 0.001) and
      tissue edema (83.0% +/- 0.3% versus 84.9% +/- 0.3%; p < 0.001) compared with
      uncontrolled reperfusion, which resulted in an injury so severe that 3 of 5 pigs
      died before the 4-hour measurements. CONCLUSIONS: After 24 hours of cold ischemia
      uncontrolled reperfusion results in a severe pulmonary reperfusion injury. This
      injury is almost completely avoided by controlling the composition (modified
      solution and white blood cell filter) and conditions (pressure) of the
      reperfusion. Because this experiment mimics the clinical situation, it suggests
      surgeons should begin to use this modality to limit reperfusion injury after lung
      transplantation.

PMID- 9768946
TI  - Detection of extrathoracic metastases by positron emission tomography in lung
      cancer.
AB  - BACKGROUND: Accurate staging of non-small cell lung cancer is essential for
      treatment planning. We evaluated in a prospective study the role of whole-body 2
      [18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in
      mediastinal nodal staging with a positive predictive value of 96%. The study was
      continued to further evaluate the value of whole-body FDG PET in detecting
      unexpected extrathoracic metastases (ETMs) in patients qualifying for surgical
      treatment by conventional staging. METHODS: One hundred patients underwent
      clinical evaluation, chest and upper abdominal computed tomography scan,
      mediastinoscopy (lymph nodes greater than 1 cm on computed tomography), and
      routine laboratory tests. In 94 patients with stage IIIa or less and 6 with
      suspected N3 a whole-body FDG PET was performed. If clinical signs of ETMs were
      present additional diagnostic methods were applied. All findings in the FDG PET
      were confirmed histologically or radiologically. RESULTS: Unexpected ETMs were
      detected in 13 (14%) of 94 patients (stage IIIa or less) at 14 sites. In addition
      6 of 94 patients were restaged up to N3 after PET. The suspected N3 disease
      (stage IIIb) on computed tomography was confirmed by PET in all 6 patients. There
      was no false positive finding of ETM. Weight loss was correlated with the
      occurrence of ETM: more than 5 kg, 5 of 13 patients (38%); more than 10 kg, 4 of
      6 patients (67%). Pathologic laboratory findings were not predictive for ETM.
      CONCLUSIONS: Whole-body FDG PET improves detection of ETMs in patients with non
      small cell lung cancer otherwise elegible for operation. In 14% of patients
      (stage IIIa or less), ETMs were detected, and in total, 20% of the patients were
      understaged.

PMID- 9768947
TI  - Leiomyosarcoma of the esophagus: results of surgical treatment.
AB  - BACKGROUND: This study examined the results of surgical treatment of
      leiomyosarcoma of the esophagus. METHODS: Between January 1920 and December 1996,
      17 patients (9 men and 8 women) with leiomyosarcoma of the esophagus were treated
      surgically at the Mayo Clinic. Median age was 58 years and ranged from 26 to 76
      years. Symptoms included dysphagia in 11 patients (64.7%) and odynophagia in 6
      (35.3%). The tumor was located in the middle third of the esophagus in 10
      patients (58.8%) and in the cervical esophagus in 7 (41.2%). Procedures performed
      included esophagogastrectomy in 9 patients (Ivor Lewis in 5, left
      thoracoabdominal in 3, and transhiatal in 1), enucleation in 3, transgastric
      excision in 1, and exploration without resection in 4. RESULTS: The procedure was
      considered curative in 11 patients (64.7%). There was one operative death
      (mortality, 5.9%). Complications occurred in 3 patients (17.6%) and included
      anastomotic leak in 2 and bleeding requiring reoperation in 1. Growth pattern was
      infiltrating in 7, polypoid in 5, and intramural in 5. Histologically, the tumor
      was grade 1 in 6 patients, grade 2 in 2, grade 3 in 7, and grade 4 in 2. The
      tumor was postsurgically classified as stage I in 2 patients, stage IIA in 7,
      stage IIB in 1, stage IIIA in 5, stage IV in 1, and unknown in 1. Six patients
      (35.3%) received adjuvant treatment. Follow-up was complete in 16 patients
      (94.1%) and ranged from 1 to 182 months (median, 48 months). Five- and 10-year
      actuarial survivals were 47.0% and 31.0%, respectively. Seven patients (41.2%)
      are currently alive (median survival, 72 months); all underwent curative
      resection. Factors affecting survival included completeness of resection, growth
      pattern, postsurgical stage, tumor grade, and tumor location (p < 0.05).
      CONCLUSIONS: We conclude that leiomyosarcoma of the esophagus is rare. Complete
      resection provides long-term survival.

PMID- 9768948
TI  - Lobectomy improves ventilatory function in selected patients with severe COPD.
AB  - BACKGROUND: Patients often undergo limited resection instead of lobectomy for non
      small cell lung cancer because of a low preoperative forced expiratory volume in
      1 second (FEV1). Our goal is to define criteria that will preoperatively identify
      a group of patients who will not lose further function after lobectomy. METHODS:
      Patients who underwent lobectomy with a preoperative FEV1 of less than 80% of
      predicted were retrospectively identified. Data collected included preoperative
      and postoperative pulmonary function tests, age, sex, the lobe resected, and
      preoperative ventilation-perfusion scan result. RESULTS: Thirty-two patients were
      included in this study. The median preoperative FEV1 was 60% of predicted (1.65
      L) and the mean change in FEV1 was a loss of 7.8% after lobectomy. The patients
      were divided into two groups. Group 1 (n = 13) had a preoperative FEV1 of less
      than or equal to 60% of predicted (median, 49%; 1.35 L) combined with an FEV1 to
      forced vital capacity ratio of less than or equal to 0.6. Group 2 (n = 19)
      includes all other patients (median preoperative FEV1, 69% of predicted; 1.87 L).
      The mean changes in FEV1 after lobectomy were +3.7% and -15.7% for groups 1 and
      2, respectively (p < 0.005). A chronic obstructive pulmonary disease index was
      defined and then calculated for each patient. The relationship between this index
      and the change in FEV1 after lobectomy for all 32 patients appears linear (r = 
      0.43; p = 0.015). CONCLUSIONS: Patients with a very low preoperative FEV1 and
      FEV1 to forced vital capacity ratio are less likely to lose ventilatory function
      after lobectomy and may actually improve it.

PMID- 9768949
TI  - Isolated lung liposome-mediated gene transfer produces organ-specific transgenic
      expression.
AB  - BACKGROUND: Gene therapy is a promising strategy for the treatment of inoperable
      pulmonary tumors and rejection after lung transplantation. However, unlike ex
      vivo administration, intravenous in vivo transfection lacks organ specificity and
      has a limited duration of expression. The objectives of this study were to limit
      transfection to a single lung and to increase the duration of gene expression in
      vivo. METHODS: Sixteen male Fisher rats were anesthetized and divided into two
      groups. Animals in group I (n = 7) received an intrajugular administration of
      1,320 microg of chloramphenicol acetyl transferase (CAT) complementary DNA
      complexed with cationic liposomes. Animals in group II (n = 9) received 660
      microg of CAT complementary DNA complexed with cationic liposomes into the
      pulmonary artery of an isolated left lung over 10 minutes. After 40 minutes of
      incubation, the lung was flushed with 10 mL of normal saline solution, and the
      perfusate was suctioned through a left pulmonary venotomy. The circulation to the
      left lung was then restored. After 48 hours, the animals were divided into
      subgroups (a and b) and CAT activity was assessed in the lungs, hearts, livers,
      and kidneys of groups Ia (n = 3) and IIa (n = 5). After 21 days, CAT activity was
      assessed in the left lungs of groups Ib (n = 4) and IIb (n = 4). RESULTS: After
      48 hours, animals that had received intravenous administration of CAT cDNA showed
      strong expression in the lungs and hearts and negligible expression in the livers
      and kidneys. In contrast, animals in group IIa, which had received isolated left
      lung perfusion of CAT cDNA showed expression only in the left lung. After 21
      days, the left lungs of animals in group Ib, which had received intravenous
      administration of CAT complementary DNA, showed no CAT expression, but the left
      lungs of animals in group IIb, which had received isolated left lung perfusion of
      CAT complementary DNA, exhibited strong CAT expression. CONCLUSIONS: Compared
      with intravenous administration, isolated lung liposome-mediated gene transfer
      provides prolonged organ-specific gene expression. This provides a useful model
      to study the effects of gene therapy on pulmonary tumors, which may have further
      application when gene therapy is used in clinical practice.

PMID- 9768950
TI  - Reoperative pulmonary metastasectomy for sarcomatous pediatric histologies.
AB  - BACKGROUND: The role for reoperative pulmonary metastasectomy in patients with
      "pediatric sarcomas" (osteosarcoma, nonrhabdomyosarcoma-soft tissue sarcoma, and
      Ewing's sarcoma) is undefined. METHODS: We reviewed our results for patients with
      these histologic presentations (median age, 17.5 years; range, 6 to 32 years)
      having two (70), three (27), or four (10) metastasectomies between January 1965
      and March 1995 to define postresection survival and potential prognostic factors.
      Simple wedges (88 thoracotomies, 84%) were performed more frequently than
      anatomic (17 thoracotomies, 16%) resections. RESULTS: With a median potential
      follow-up of 12.7 years, median survival was 2.25, 3.60, and 0.96 years from the
      second, third, and fourth explorations, respectively. Primary tumor site, sex,
      histology, age, maximal metastasis size, and systemic chemotherapy did not
      influence survival. Resectability was the most important prognostic factor (5.6
      versus 0.7 years, 5.2 versus 2.5 years, 2.2 versus 0.2 years, resectable versus
      unresectable, median survival from second, third, and fourth thoracotomy,
      respectively). Unresectability, disease-free interval less than 6 months between
      initial (ie, first) pulmonary resection and the second thoracotomy, and two or
      more preoperative nodules noted on the right were simultaneously negatively
      associated with survival from the second thoracotomy. Unresectability or finding
      two or more metastases negatively affected survival from the third thoracotomy.
      CONCLUSIONS: These data imply that repeat metastasectomy can salvage a subset of
      patients with sarcomatous pediatric histologic presentations who retain favorable
      prognostic determinants.

PMID- 9768951
TI  - Standardized clinical care pathways for major thoracic cases reduce hospital
      costs.
AB  - BACKGROUND: Standardized clinical care pathways have been developed for
      postoperative management in an attempt to contain costs in an era of rising
      health care costs and limited resources. The purpose of this study was to assess
      the effect of these pathways on length of stay, hospital charges, and outcome for
      major thoracic surgical procedures. METHODS: All anatomic lung (segmentectomy,
      lobectomy, and pneumonectomy) and partial and complete esophageal resections
      performed from July 1991 to July 1997 were retrospectively analyzed for length of
      stay, hospital charges, and outcome. A prospectively developed database was used.
      Clinical care pathways were introduced in March 1994. Comparisons were made
      between the procedures performed before (group I) and after (group II) pathway
      implementation. Common to both pathways are early mobilization and prudent x-ray
      and laboratory analysis. In addition, the pathway for esophagectomies emphasizes
      overnight intubation with 24-hour intensive care unit care, and staged diet
      advancement. The discharge goal was postoperative day 10. For lung resection the
      emphasis is early postoperative extubation with overnight intensive care unit
      management. The discharge goal was postoperative day 7. RESULTS: Group I
      esophagectomies (n = 56) had significantly greater hospital charges compared with
      group II (n = 96) ($21,977 +/- $13,555 versus $17,919 +/- $5,321; p < 0.04, in
      actual dollars) and ($29,097 +/- $18,586 versus $19,260 +/- $6,000; p < 0.001, in
      dollars adjusted for inflation) and greater length of stay (13.6 +/- 6.9 versus
      9.5 +/- 2.8 days; p < 0.001). Group I lung resections (n = 185) had a
      significantly greater length of stay compared with group II (n = 241) (8.0 +/-
      6.2 versus 6.4 +/- 3.8 days; p < 0.002); although charges trended downward
      ($13,113 +/- $10,711 versus $12,404 +/- $7,189; not significant) in actual
      dollars, charges were significantly less in dollars adjusted for inflation
      ($17,103 +/- $13,211 versus $13,432 +/- $8,056; p < 0.01). The most significant
      decreases in charges for esophagectomies were in miscellaneous charges (61% in
      dollars adjusted for inflation), pharmaceuticals (60%), laboratory (42%) and
      radiologic (39%) tests, physical therapy charges (35%), and routine charges
      (34%). For lung resections the greatest savings occurred for pharmaceuticals
      (38%), supplies (34%), miscellaneous charges (25%), and routine charges (22%).
      Mortality was similar (esophagectomies: I, 3.6%; II, 0%; lung resections: I,
      0.5%; II, 0.8%; not significant). CONCLUSIONS: Introduction of standardized
      clinical pathways has resulted in a marked reduction of length of stay for all
      major thoracic surgical procedures. Total charges were reduced for both
      esophagectomies (34%) and lung resections (21%) with continued quality of
      outcome.

PMID- 9768952
TI  - Axillary lymph node metastases from bronchogenic carcinoma.
AB  - BACKGROUND: Axillary lymph node metastases (ALNMs) from bronchogenic carcinoma
      are rare and their significance may be questioned. A surgical approach may allow
      a better understanding of the mechanism of their occurrence. METHODS: A
      retrospective study of 1,486 cases of surgically removed non-small cell lung
      carcinoma was performed. Twenty-two patients (1.5%) had extrathoracic nodal
      metastases. Nine of them were ALNMs (<1%). These cases form the basis of this
      study. RESULTS: In 1 patient ipsilateral ALNM was removed during a lung
      operation. It was a left non-small cell lung carcinoma invading the chest wall
      (T3 N2). In the other patients (n = 8) ALNMs were observed during postoperative
      follow-up; 4 underwent ALNM resection, 2 had radiotherapy, and 2 had symptomatic
      treatment only. For these 8 patients, in the TNM classification performed after
      an initial bronchogenic carcinoma operation, the lymph node status was,
      respectively, N0 in four cases, N1 in three cases, and N2 in one case. Survival
      ranged from 1 to 10 months, except for one patient who is still alive after more
      than 5 years. In this case, the ALNM was discovered 4 months after a right lower
      lobectomy for a T2 N0 adenocarcinoma. CONCLUSIONS: Axillary lymph node metastases
      may be involved through direct chest wall invasion of bronchogenic carcinoma or
      retrograde spread from supraclavicular lymphnode block. However, another
      mechanism seems to be the systemic vascular route.

PMID- 9768953
TI  - Endoscopic treatment of postoperative bronchopleural fistula: experience with 45
      cases.
AB  - BACKGROUND: The value of bronchoscopic sealing of bronchopleural fistulas was
      studied retrospectively. METHODS: The cases of 45 patients seen between 1983 and
      1996 with bronchopleural fistula after pneumonectomy (40 patients) or lobectomy
      (5 patients) were reviewed. Age, underlying disease, side, fistula size
      (millimeters) at initial bronchoscopy, survival (days) after endoscopic
      treatment, mode and number of endoscopic interventions, interval (days) between
      operation and fistula occurrence, and pathologic TNM stage in the case of
      malignancy were recorded. On the basis of the therapeutic outcome (cure, death,
      chronic empyema with closed fistula, or chronic empyema with open fistula) and
      the modality (successful sealing or bronchoscopic failure with subsequent
      surgical intervention), various groups were assessed and compared. RESULTS: Of 29
      patients (64%) treated only endoscopically, 9 were cured. Seven patients had
      fistula closure, but persistent chronic empyema necessitated permanent drainage.
      In another 7 patients, the fistula remained open and also was controlled by
      permanent drainage. Six patients in this group died. The overall rate of fistula
      closure was 35.6% (16 patients), and recurrence occurred in 2 patients. Sixteen
      patients (35.6%) required surgical intervention because of increasing fistula
      size (8 patients), sepsis with refractory empyema (7), and fecal empyema (1
      patient). Two patients in the surgical group died. Small fistulas (<3 mm)
      responded particularly well to primary endoscopic treatment. CONCLUSIONS:
      Bronchoscopic treatment of bronchopleural fistula appears an efficient
      alternative, especially when surgical intervention cannot be done because of the
      physical condition of the patient.

PMID- 9768954
TI  - Tracheal mucoepidermoid carcinoma in a 7-year-old child.
AB  - Mucoepidermoid cancers are rare tumors that arise from the serous and mucous
      glands of the upper airway and salivary glands. Patients, especially children,
      with tumors that arise in the trachea and upper airways are often misdiagnosed as
      asthmatic and are treated with bronchodilators without resolution. A 7-year-old
      girl who had been diagnosed as asthmatic was subsequently found to have a
      mucoepidermoid tumor of the trachea. She underwent a successful tracheal
      resection and remains tumor free on follow-up bronchoscopy at 16 months.

PMID- 9768955
TI  - An unexpected complication after harvesting of the radial artery for coronary
      artery bypass grafting.
AB  - Acute ischemia of the hand developed after coronary artery bypass grafting with a
      radial artery conduit. Perioperative tests established that there was good
      perfusion to the hand via the collateral vessels. Angiographic examination showed
      an absence of the ulnar artery. Circulation was restored with a vein graft. I
      briefly review noninvasive investigations available and suggest that color
      Doppler scanning should be routinely performed before the use of the radial
      artery as a conduit.

PMID- 9768956
TI  - Interleukin-6 and "complex" cardiac myxoma.
AB  - A rare case of "complex" cardiac myxoma is reported. Complex cardiac myxoma
      manifests with more constitutional signs than the sporadic type. These
      constitutional signs are known to be associated with the overproduction of
      interleukin-6 by cardiac myxomas. In our study, immunohistochemical staining of
      the myxoma for interleukin-6 was strongly positive. The serum interleukin-6 level
      decreased after surgical removal of the tumor and has remained undetectable for
      the past 2 years.

PMID- 9768957
TI  - Extracardiac Fontan operation with tube fenestration allowing transcatheter coil
      occlusion.
AB  - A fenestration may improve the immediate postoperative course after a Fontan
      procedure by preserving the cardiac output. We describe a simple and safe
      technique of fenestration amenable to coil occlusion, which can be carried out in
      most cardiac catheterization laboratories.

PMID- 9768958
TI  - Absent aortic valve: successful palliation in the neonate.
AB  - A successful palliation of a neonate with absent aortic valve in hypoplastic left
      heart syndrome is reported.

PMID- 9768959
TI  - Successful repair of aortoesophageal fistula secondary to traumatic
      pseudoaneurysm.
AB  - There have previously been only rare reported survivors of an aortoesophageal
      fistula resulting from a traumatic pseudoaneurysm. We report a case of a young
      man with a dramatic presentation who was successfully managed by immediate
      operative repair. A prosthetic graft was sewn within the sac of the aneurysm,
      with the aneurysm wall being used to protect the graft, and the esophagus was
      resected. Staged reconstruction of the esophagus was subsequently performed
      successfully. The patient is now alive and well 2 1/2 years later.

PMID- 9768960
TI  - Surgical retrieval of an embolized central venous catheter in a premature baby.
AB  - Embolization of central venous catheter fragments is usually treated with
      percutaneous interventional techniques, which are difficult to apply in infants
      with very low birth weight. We surgically removed a catheter fragment in a
      preterm neonate, to avoid the impending thrombosis of the right pulmonary artery.
      The operation was performed with a nerve hook introduced through a tiny incision
      in the vessel's wall. The procedure was well tolerated, and no stricture remains
      at the site of incision.

PMID- 9768961
TI  - Tracheal obstruction in achalasia: a role for airway stenting?
AB  - We describe an 82-year-old woman who presented with acute tracheal obstruction
      secondary to advanced, asymptomatic achalasia. Conventional treatment of her
      achalasia failed to relieve recurrent episodes of airway obstruction requiring
      endotracheal intubation. Because she was not fit for an operation, a Gianturco
      endotracheal stent was placed bronchoscopically. She remains without respiratory
      or upper gastrointestinal symptoms 2 years later. Recent information regarding
      the pathophysiology and surgical treatment of this complication is reviewed.

PMID- 9768962
TI  - A taste of Chinese medicine!
AB  - We report a case of profound anticoagulation caused by interaction between
      warfarin and danshen, a widely used Chinese herbal medicine, in a patient who had
      undergone mitral valve replacement. Patients taking warfarin should be warned not
      to take this herb. In addition, physicians should be alert to the possibility of
      an interaction with herbal medicine when anticoagulation control becomes
      difficult and no other causes are apparent.

PMID- 9768963
TI  - Double-outlet right ventricle with complete atrioventricular canal.
AB  - A case of double-outlet right ventricle, unbalanced complete atrioventricular
      canal, hypoplastic aortic arch, coarctation of the aorta, and atrioventricular
      valve regurgitation was treated with a staged approach. At 4 days of life the
      patient underwent aortic arch repair, atrial septectomy, common atrioventricular
      valve regurgitation repair, and pulmonary artery banding. When she was 14 months
      of age a biventricular repair was accomplished by two-patch complete
      atrioventricular canal repair and arterial switch procedure.

PMID- 9768964
TI  - Surgical resection of lung cancer originating in a tracheal bronchus.
AB  - We experienced a case of lung cancer that developed from a tracheal bronchus in
      an 80-year-old man. The tumor was completely resected by right upper lobectomy
      and resection of the tracheal bronchus as well as dissection of the mediastinal
      lymph nodes. Postsurgical pathologic staging was stage IB (T2 N0 M0)
      adenocarcinoma.

PMID- 9768965
TI  - Surgical management of superior vena caval syndrome in sarcoidosis.
AB  - Sarcoidosis causing the superior vena caval syndrome has been only rarely
      documented in the literature. We report surgical management of this problem with
      a spiral vein graft.

PMID- 9768966
TI  - Inflammatory pseudotumors of the lung.
AB  - Two unusual cases of inflammatory pseudotumors in young female patients are
      described. One presented with massive hemoptysis and a solitary circumscribed
      mass treated with urgent lobectomy. The second presented initially with cough and
      a small right lower lobe mass. She presented again, 8 years later, with a lung
      mass so expanded as to necessitate a pneumonectomy with partial resection of
      surrounding structures. Both cases indicate the need for early and complete
      removal of the inflammatory pseudotumors.

PMID- 9768967
TI  - Purposeful delay in the repair of a traumatic rupture of the aorta with
      coexistent liver injury.
AB  - Purposeful delay in the repair of traumatic aortic injury by appropriate medical
      management is indicated when the risk of immediate thoracotomy is high. A grade V
      liver injury implies parenchymal disruption of greater than 75% of a hepatic
      lobe. We report the successful management of a patient with a class IB proximal
      descending aortic transection and concomitant grade V liver injury that precluded
      aortic repair until its resolution.

PMID- 9768968
TI  - Tophaceous pseudogout of the mitral valve.
AB  - This report describes a 61-year-old patient on chronic hemodialysis with
      multiple, left-sided, intracardiac masses causing intermittent coronary
      obstruction. Mitral valve replacement was performed. Massive deposition of
      calcium pyrophosphate crystals in and around the valve cusps led to the diagnosis
      of tophaceous pseudogout (tumoral calcinosis) of the mitral valve.

PMID- 9768969
TI  - Cardiomyoplasty after implantation of a pacemaker and cardioverter/defibrillator.
AB  - Presently, a combination of two surgical methods improves the survival of
      patients with advanced ventricular dysfunction: implantable
      cardioverter/defibrillator implantation (which prevents sudden cardiac death) and
      cardiomyoplasty (which prevents further dilatation of the heart and provides
      additional cardiac assistance). We report the clinical course of a patient who
      had cardiomyoplasty after cardioverter/defibrillator implantation and pacemaker
      insertion. It is a rare case in which three different devices
      cardioverter/defibrillator, pacemaker, and cardiomyostimulator) are functioning
      together without crosstalk.

PMID- 9768970
TI  - Reversible snaring for proper prosthetic seating during valve replacement.
AB  - A method of reversible suture snaring is described for evaluating the final valve
      seating and positioning before knot tying of valve sutures. This allows for
      alteration of the operative plan before investing substantial ischemic time in a
      nonfunctional result. The procedure has been used in 577 consecutive prosthetic
      valve replacements in the past 5 years. The technique maintains proper seating
      while the valve is permanently anchored in place.

PMID- 9768971
TI  - Advancement flaps to treat superficial wound infections after cardiac operations.
AB  - The management of superficial sternal wound infections is not well-codified. In
      case of large necrosis or tissue defect we use a two-stage approach, consisting
      of a first surgical debridement, followed a few days later by wound closure by
      means of two lateral advancement flaps. We have used this technique with good
      cosmetic results and shorter hospital stays.

PMID- 9768972
TI  - Hybrid-type stabilizer for off-pump direct coronary artery bypass grafting.
AB  - We have developed a mechanical stabilizer for use in off-pump direct coronary
      artery bypass grafting. We consider it an improvement on the sucker-type
      stabilizer, although it uses the mechanisms of the compressor-type. Our hybrid
      stabilizer effectively immobilizes the local heart surface with light compression
      and low evacuation. We believe that its use will eliminate the need for further
      immobilization and thus reduce cardiac invasiveness.

PMID- 9768973
TI  - Improved visualization in minimally invasive coronary bypass grafting.
AB  - A special surgical technique is required for minimally invasive coronary artery
      bypass grafting, particularly under beating-heart conditions. We describe a very
      simple system that provides improved visualization of the surgical site.

PMID- 9768974
TI  - Counteracting paradoxical motion in videoendoscopic operations.
AB  - Paradoxical motion during videoendoscopic operations is generated when the camera
      and instruments are on opposite sides of the targeted pathology. This is
      occasionally difficult to avoid when operating on a wide field. We have found
      that turning the camera 180 degrees restores the normal spatial relationship.
      This simple maneuver allows the operator to use the existing camera and
      instrument ports to his or her best ergonomic advantage.

PMID- 9768975
TI  - Accurate length adjustment of aortocoronary saphenous vein bypass grafts.
AB  - We describe a simple method for tailoring the length of aortocoronary saphenous
      vein grafts. The objective is to prevent any kinking of the these grafts, which
      may compromise blood flow in them and lead to their early occlusion.

PMID- 9768976
TI  - Coronary artery bypass grafting in patients with cerebrovascular disease.
AB  - The incidence of carotid artery disease in patients undergoing coronary artery
      bypass grafting appears to be increasing as our population ages. The optimal
      treatment for these high-risk patients with concomitant carotid and coronary
      artery disease remains controversial. This review focuses on the management of
      patients with coexistent carotid and coronary arteriosclerosis. The significance
      and management of the patient with an asymptomatic carotid stenosis in patients
      undergoing coronary artery bypass grafting and the role of combined coronary
      artery bypass grafting and carotid endarterectomy in these patients will be
      discussed.

PMID- 9768977
TI  - Circulatory support devices for bridge to recovery.

PMID- 9768978
TI  - As originally published in 1992: Skeletal muscle ventricles in the pulmonary
      circulation: up to 16 weeks' experience. Updated in 1998.

PMID- 9768979
TI  - Severe truncal valve dysplasia: association with DiGeorge syndrome?

PMID- 9768980
TI  - What is "minimally invasive"?

PMID- 9768981
TI  - Severe postoperative hemorrhage after neoadjuvant chemotherapy for invasive
      thymoma.

PMID- 9768982
TI  - Angioscopic pulmonary embolectomy and ECMO.

PMID- 9768983
TI  - Omental transplantation for vascular myelopathy caused by an aortic operation.

PMID- 9768984
TI  - Why aren't valve sizers and prostheses labeled accurately?

PMID- 9768985
TI  - How high should mammary artery be harvested for the minimally invasive approach?

PMID- 9768986
TI  - Retrograde autologous priming reduces blood use.

PMID- 9768987
TI  - Surgical procedure for bilateral lung and liver hydatid cysts.

PMID- 9768988
TI  - Repeated pulmonary metastasectomy.

PMID- 9768989
TI  - The LAST operation: techniques and results before and after the stabilization
      era.
AB  - BACKGROUND: Left anterior descending artery stabilization allows performance of
      left internal mammary artery grafting via a left anterior small thoracotomy on a
      beating heart. Our surgical experience was reviewed to assess if surgical results
      have improved as result of specialized instrumentation. METHODS: Of 545 patients
      who had the left anterior small thoracotomy operation, 261 underwent this
      procedure for single left anterior descending artery disease. Two groups were
      considered, before and after the use of specialized instrumentation: group A (n =
      93), operated on from November 21, 1994, to April 20, 1996; and group B (n =
      168), operated on from April 21, 1996, to December 1997. RESULTS: Early mortality
      was similar in the two groups. The further revascularization (operation or
      percutaneous transluminal coronary angioplasty) and the rate of occlusion of the
      conduit were higher in group A, whereas anastomotic or conduit malfunction was
      not. Cumulating angiography and Doppler flow evaluation, 92.5% of the anastomoses
      in group A and 98.8% in group B (p = 0.026) were patent, and 90.3% in group A and
      97.6% in group B (p = 0.031) were patent and not restrictive. At 19 months,
      survival was similar, but the event-free survival was higher in group B.
      CONCLUSIONS: Both left anterior descending artery stabilization and safer left
      internal mammary artery harvesting contributed to improve angiographic and
      clinical results after the left anterior small thoracotomy operation.

PMID- 9768990
TI  - Safety and cost-effectiveness of MIDCABG in high-risk CABG patients.
AB  - BACKGROUND: Myocardial revascularization without cardiopulmonary bypass has been
      proposed as a potential therapeutic alternative in high-risk patients undergoing
      coronary artery bypass grafting. To evaluate this possibility we compared 15 high
      risk (HR) patients in whom minimally invasive direct coronary artery bypass
      grafting was used as the method of revascularization with 41 consecutive patients
      who underwent conventional coronary artery bypass grafting during 1 month.
      METHODS: Patients undergoing myocardial revascularization without cardiopulmonary
      bypass were significantly older than their low-risk (LR) counterparts (72.2 +/-
      11.6 versus 63.3 +/- 9.7 years, p = 0.006). The demographic profile for HR versus
      LR patients was as follows: female patients, 60.0% versus 26.8%, p = 0.02;
      diabetes, 20.0% versus 24.4%, p = 0.7; prior stroke, 33.3% versus 7.4%, p = 0.03;
      chronic obstructive pulmonary disease, 60.0% versus 9.8%, p < 0.0001; peripheral
      vascular disease, 33.3% versus 12.2%, p = 0.03, congestive heart failure, 26.6%
      versus 9.8%, p = 0.09; impaired left ventricular (ejection fraction < 0.40),
      40.0% versus 17.0%, p = 0.07; urgent operation, 86.6% versus 46.3%, p < 0.0001;
      and redo operation, 20.0% versus 0%, p = 0.003. RESULTS: There were no deaths in
      the HR group and one death in the LR group. The average intensive care unit stay
      was 1.1 +/- 0.5 days in HR patients versus 1.6 +/- 1.6 days in LR individuals (p
      = 0.2), and the average hospital stay was 6.1 +/- 1.8 versus 7.3 +/- 4.4 days,
      respectively (p = 0.3). We used an acuity risk score index developed by the Adult
      Cardiac Care Network of Ontario to predict outcome in the HR group. The expected
      intensive care unit stay in HR patients was 4.1 +/- 1.2 days (versus the observed
      stay of 1.1 +/- 0.5 days, p < 0.0001), and the expected hospital stay was 12.5 +/
      1.5 days (versus the observed stay of 6.1 +/- 1.8 days, p < 0.0001). The
      expected mortality in the HR group was 6.1% versus 0%, p = 0.3. A cost regression
      model was used to examine predicted versus actual cost (in Canadian dollars) for
      the HR patient cohort (based on Ontario Ministry of Health funding). The expected
      cost for the HR cohort would have been $11,997 per patient. In contrast, the
      average cost for these 15 patients was $5,997 per patient, an estimated cost
      saving of 50%. CONCLUSIONS: Myocardial revascularization without cardiopulmonary
      bypass appears to be a safe and cost-effective therapeutic modality for HR
      patients requiring myocardial revascularization.

PMID- 9768991
TI  - Left anterior descending coronary artery bypass grafting through minimal
      thoracotomy.
AB  - BACKGROUND: In recent years, minimally invasive direct coronary artery bypass
      grafting has emerged as a valid tool for revascularization in a select group of
      patients with severe lesions of the left anterior descending coronary artery.
      Here we report the clinical results using two devices designed by us to
      facilitate the harvesting of the left internal mammary artery up to its origin
      and to occlude and stabilize the left anterior descending coronary artery while
      placing the anastomosis. METHODS: From January 1996 to January 1998, 122 patients
      underwent minimally invasive direct coronary artery bypass grafting in the
      Department of Cardiac Surgery, Favaloro Foundation. One hundred twelve patients
      received a single left internal mammary artery-left anterior descending coronary
      artery bypass graft, and in 10 patients, an additional bypass graft was
      performed. RESULTS: Most patients were discharged on day 2 or 3 after the
      procedure. Three patients (2.5%) had a perioperative myocardial infarction. The
      overall hospital mortality rate was 3.3% (4 patients). CONCLUSIONS: The
      combination of team experience, more careful dissection of the left internal
      mammary artery up to its origin, and use of the stabilizer-occluder and
      interrupted suture technique for the anastomosis has markedly improved our
      results.

PMID- 9768992
TI  - Thoracoscopic harvest of the internal thoracic artery: a multicenter experience
      in 218 cases.
AB  - BACKGROUND: Off-pump bypass grafting most commonly involves harvest of the left
      internal thoracic artery (ITA) through a minithoracotomy under direct vision.
      Disadvantages to this approach, however, include poor exposure, incomplete
      dissection resulting in inadequate ITA length, and significant postoperative pain
      because of rigorous chest retraction. This study determined the safety and
      efficacy of an alternative to direct ITA harvest using a thoracoscopic approach.
      METHODS: Two hundred eighteen patients at three institutions underwent
      thoracoscopic ITA harvest; 118 (54%) for off-pump coronary bypass grafting.
      RESULTS: The left ITA was harvested in 211 patients (96%); the mean harvest time
      ranged from 42 to 55 minutes. The ITA was injured in 4 patients (1.8%), and
      conversion to open ITA harvest occurred in 18 (8%). Complications included
      intercostal neuropathy (4), reoperation for ITA bleeding (2), phrenic nerve
      injury (1), and wound infection (1). CONCLUSIONS: This large, multicenter
      experience demonstrates that thoracoscopic harvest of the ITA can be accomplished
      safely and within a reasonable time frame in most patients undergoing coronary
      bypass grafting.

PMID- 9768993
TI  - Minimally invasive surgical treatment of coronary artery multivessel disease.
AB  - BACKGROUND: If coronary artery multivessel disease is the target of a minimally
      invasive procedure, either median sternotomy or cardiopulmonary bypass can be
      avoided. METHODS: We used an alternate technique instead of minithoracotomy and
      cardiopulmonary bypass to treat 102 patients (82 men, 20 women; age range, 39 to
      82 years; median, 61.0 +/- 8.9 years) for coronary artery single-vessel, double
      vessel, or multivessel disease between November 1996 and January 1998. Twenty
      nine patients (22 men, 7 women; age range, 46 to 78 years; median, 69.0 +/- 8.4
      years), who were in a high-risk group for the development of perioperative
      complications because of the use of cardiopulmonary bypass, received median
      sternotomy and a beating heart procedure using the Octopus stabilizing technique.
      The left anterior descending coronary artery was the target vessel in all
      patients except for 1, in whom the left internal mammary artery was used.
      RESULTS: There was no intraoperative death in either series. In the beating heart
      group (Octopus) 2 patients died on postoperative day 31 and 35, respectively, of
      postoperative pneumonia. CONCLUSIONS: Both techniques present safe alternative
      procedures to conventional coronary artery bypass grafting in patients with
      coronary artery multivessel disease.

PMID- 9768994
TI  - Minimally invasive coronary artery bypass grafting without cardiopulmonary
      bypass: early experience and follow-up.
AB  - BACKGROUND: There is renewed interest in coronary artery bypass grafting without
      cardiopulmonary bypass using the anterolateral minithoracotomy approach. We
      evaluated 209 patients who underwent minimally invasive direct coronary artery
      bypass grafting using an anterolateral minithoracotomy. The anastomosis was
      performed under direct vision on the beating heart without using cardiopulmonary
      bypass. METHODS: The procedure was performed using a 6- to 9-cm left (or right)
      anterolateral thoracotomy for internal thoracic artery graft harvesting and
      anastomosis. Different devices were used for local immobilization. In 195
      patients a single internal thoracic artery to left anterior descending coronary
      artery bypass was performed, in 3 patients a single right internal thoracic
      artery to right coronary artery bypass, and in 11 patients the radial artery was
      used together with the internal thoracic artery as a T-graft. RESULTS: Conversion
      to sternotomy or cardiopulmonary bypass was necessary in 10 (4.7%) patients.
      Intraoperative myocardial infarction was observed in 4 patients (1.9%). Early
      postoperative redo operation was necessary in 5 patients (2.4%). Mortality was
      0.47%. Postoperatively, 191 patients (91.3%) underwent angiography for graft
      patency control. The overall patency rate was 97.3%. Minor stenosis of the
      internal thoracic artery graft was observed in 18 patients (9.4%); moderate
      stenosis was observed in 5 patients (2.6%). Midterm angiographic follow-up after
      6 months was performed in 58 patients. The patency rate was 98.2%. One patient
      with severe symptomatic stenosis (1.7%) underwent reoperation. CONCLUSIONS: With
      the help of the local immobilization systems off-pump coronary artery bypass
      grafting was safely performed through a minithoracotomy. The incidence of
      intraoperative and postoperative complications was low and follow-up showed good
      results. Thus, minimally invasive direct coronary artery bypass grafting is an
      excellent technique for arterial revascularization in patients having symptomatic
      left anterior descending coronary artery disease.

PMID- 9768995
TI  - Minimally invasive saphenous vein harvesting.
AB  - BACKGROUND: Minimally invasive techniques to harvest the saphenous vein for
      coronary artery bypass grafting continue to improve and evolve. Smaller cutaneous
      incisions have been shown to decrease postoperative discomfort and improve
      healing. We describe a technique involving carbon dioxide insufflation and
      endoscopic dissection to allow easier and atraumatic dissection. METHODS: The
      VasoView endoscope system (Origin Medsystems, Inc) was used to harvest the
      saphenous vein for coronary artery bypass grafting in 27 patients. This group was
      compared with 24 patients having traditional saphenous vein harvesting. Wounds
      were examined for complications daily. Pain and postoperative mobility were
      quantified independently by physical therapists. RESULTS: Comparison of patients
      in the two groups revealed greater edema in the legs with traditional harvesting.
      Patients with endoscopic removal also had less pain and increased mobility
      postoperatively. On average, minimally invasive harvesting allowed patients to
      ambulate to a predischarge goal of 300 ft 2 days earlier. CONCLUSIONS: Minimally
      invasive harvesting of the saphenous vein by insufflation techniques is safe,
      effective, and atraumatic to the conduit. Discomfort is minimized, promoting
      earlier and improved ambulation.

PMID- 9768996
TI  - Feasibility study of a mechanical suturing device for less invasive mitral
      operations.
AB  - BACKGROUND: Because of smaller incisions and limited exposure, less invasive
      operations on the mitral valve can be arduous and time-consuming. This study
      examined the feasibility of a mechanical suturing device to facilitate less
      invasive mitral replacement. METHODS: Five mongrel dogs underwent limited left
      thoracotomy. After conventional cardiopulmonary bypass and cardioplegia, the
      mitral valve was exposed through a left atriotomy. After excision of the anterior
      leaflet, subannular sutures were placed using a mechanical suturing device. This
      device simultaneously passes two ends of a pledgeted 2-0 braided suture through
      the valvular annulus, then mechanically grasps both needles on the atrial aspect.
      Hence, a mattress suture is accomplished one-handed in a single continuous
      motion. This procedure was repeated around the entire annulus. A mechanical valve
      was seated and the sutures were tied and cut. RESULTS: All mechanical valves were
      implanted successfully. In the 4 animals in which it was attempted,
      cardiopulmonary bypass was successfully weaned. No evidence of perivalvular leak
      was observed by echocardiography. CONCLUSIONS: These data establish the
      feasibility of a mechanical suturing device for operations on the mitral valve.
      The device is easily mastered, maintains precise spacing between sutures, and
      permits rapid placement of mattress sutures. We predict widespread application
      for both less invasive and conventional valve operations.

PMID- 9768997
TI  - Coronary artery bypass on the beating heart with the Octopus: a North American
      experience.
AB  - BACKGROUND: The practice of minimally invasive coronary artery bypass grafting
      remains controversial. This study outlines the results of single and multiple
      vessel bypass performed using the Medtronic Octopus Tissue Stabilization System
      and beating heart techniques. Results are compared with those of a standard
      cardiopulmonary bypass group. METHODS: The group included 89 patients having
      operations performed during a 10-month period with average follow-up of 162.3
      days. Complications, length of stay, and functional status were recorded.
      Postoperative stress testing and angiograms were performed selectively. RESULTS:
      The average age was 62.3 years and the average ejection fraction was 0.65. Twenty
      five percent of the patients underwent operations urgently or emergently,
      averaging 1.8 grafts/patient. In 83 of 89 patients operations were completed
      without cardiopulmonary bypass using the Octopus without mortality. Morbidities
      were statistically similar to a group of 369 cardiopulmonary bypass patients.
      Postoperative length of stay was shorter in the Octopus group (p = 0.005).
      CONCLUSIONS: The Octopus provided predictable, reproducible immobilization with
      short-term results comparable with those obtained with standard cardiopulmonary
      bypass.

PMID- 9768999
TI  - Facilitated vascular anastomoses: the one-shot device.
AB  - BACKGROUND: A mechanical system for facilitating vascular anastomosis (end-to
      side, end-to-end) is described that enables the rapid construction of
      nonpenetrated, compliant junctions. The instrument (United States Surgical One
      Shot system) simultaneously applies either 10 or 12 nonpenetrating, arcuate
      legged titanium clips to everted vessel or prosthetic conduit edges. METHODS AND
      RESULTS: The instrument has been tested in animals (jugular and femoral vein jump
      grafts in carotid and femoral arteries, interpositional grafts, 20 pigs) and
      human cadaveric constructs (saphenous veins to left anterior descending coronary
      arteries, 20 cases, 5 brachiocephalic access fistulas) as end-to-side constructs.
      Clipped constructs have equivalent or superior physical properties to control
      sutured constructs (6-0 polypropylene) as gauged by burst and tensile strength.
      All studies were performed under Food and Drug Administration Good Laboratory
      Practice standards, and the device has been approved for marketing by the Food
      and Drug Administration. CONCLUSIONS: The device enables rapid and reproducible
      vascular anastomotic constructs with vessels as small as 1.8 mm outer diameter.
      The constructs are flanged, interrupted, and nonpenetrated.

PMID- 9768998
TI  - Minimally invasive coronary artery bypass grafting: port-access approach versus
      off-pump techniques.
AB  - BACKGROUND: Within the past 5 years several surgical techniques have been
      developed for less invasive surgical treatment of coronary artery disease. The
      aim of this study was to define specific indications for the various minimally
      invasive coronary artery surgical procedures. METHODS: Minimally invasive direct
      coronary artery bypass grafting through a minithoracotomy was performed in 67
      patients. The left internal mammary artery was anastomosed on the beating heart
      with the use of a pressure or suction stabilizer without the use of
      extracorporeal circulation. In 58 other patients with multivessel disease, the
      off-pump coronary artery bypass grafting technique through a sternotomy was
      applied with a left internal mammary artery to left anterior descending artery
      and additional vein grafts without extracorporeal circulation. In a third group,
      Port-Access (Heartport Inc, Redwood City, CA) coronary artery bypass grafting was
      performed through a left minithoracotomy with the use of an endovascular
      extracorporeal circulation system and cardioplegic arrest. Angiographic follow-up
      was complete in 64% of the patients. RESULTS: There was minimal perioperative or
      postoperative mortality (0.5%). The medium surgical procedure time for all
      minimally invasive and off-pump procedures was 2.5 hours; it was 4.5 hours for
      Port-Access procedures. The median postoperative intensive care unit stay was 1.0
      days, and the median hospitalization was 5.0 days. Overall graft patency was
      97.3%; in 8 patients (4.1%) a stenosis either at or distal to the graft
      anastomosis was dilated with coronary angioplasty. CONCLUSIONS: For single-vessel
      disease of the left anterior descending artery, the minimally invasive coronary
      artery bypass grafting procedure can be performed safely without the use of
      extracorporeal circulation. In case of hemodynamic instability or anatomic
      variation, the Port-Access procedure can be applied without additional necessity
      for sternotomy. For multivessel disease, the off-pump bypass grafting procedure
      with sternotomy can be recommended depending on the coronary arteries involved.
      In case of necessary grafts to the lateral marginal or circumflex branches, Port
      Access grafting can be recommended and may play an important role in the future
      for the development of fully endoscopic robot-assisted coronary artery bypass
      grafting.

PMID- 9769000
TI  - Beyond stents: third-generation coronary devices.
AB  - Despite extraordinary growth in percutaneous transluminal coronary angioplasty
      (>400,000 cases in United States in 1997) patients are still routinely referred
      for bypass grafting in large numbers. Why? Second-generation devices (directional
      coronary atherectomy, high-speed rotational atherectomy [Rotablator], and stents)
      have expanded the application of percutaneous catheter treatment of coronary
      disease. Specifically, highly eccentric lesions in large vessels, heavily
      calcified lesions, and coronary dissections can be effectively treated with these
      devices. Stents have substantially reduced the incidence of restenosis, but this
      benefit is largely confined to vessels more than 3 mm in diameter and stenoses
      less than 20 mm in length. A third generation of coronary devices has evolved in
      the late 1990s in response to continuing failures of conventional balloon
      angioplasty, atherectomy, and stenting. The failures of the 1990s were (1)
      restenosis, including in-stent restenosis, (2) chronic total occlusions, (3)
      diffuse small-vessel disease, and (4) aged vein graft disease. In response to
      these challenges novel devices are being developed: (1) for restenosis,
      intracoronary radiation therapy (brachytherapy); (2) for chronic total
      occlusions, Prima Laser wire; (3) for diffuse small-vessel disease, percutaneous
      myocardial laser revascularization; and (4) for aged vein grafts,
      antiembolization devices. Each of these new catheter technologies will need to be
      economically and clinically reconciled with the multitude of minimally invasive
      surgical revascularization techniques that are rapidly evolving.

PMID- 9769001
TI  - Less invasive cardiac operations through a median sternotomy: 100 consecutive
      cases.
AB  - BACKGROUND: In the beginning of 1997, we developed a routine approach to
      intracardiac operations through a less invasive median sternotomy. A limited (6
      to 9 cm) median skin incision followed by a subcomplete (manubrium and body)
      median sternotomy makes opening and closing of the chest easier; conventional
      central cardiopulmonary bypass is instituted, and no modifications to the
      surgical techniques are necessary. METHODS: In 100 consecutive patients (mean
      age, 62.04 years; range, 9 to 92 years), 70 aortic, 13 mitral, and 17 other
      cardiac procedures were performed. Surgical technique required many self-made
      instruments; anesthetic "fast-tracking" management was performed. RESULTS: Four
      patients died. One conversion to a standard sternotomy and five reoperations for
      bleeding were necessary. Cross-clamp time ranged from 33 to 140 minutes (mean +/-
      standard deviation, 69.23 +/- 20.99 minutes) and total drainage loss ranged from
      120 to 1,800 mL x m(-2) x 24 h(-1) (mean, 288 mL x m(-2) x 24 h(-1)). The
      postoperative course was shorter than usual, and one complication in the healing
      wound was observed. The scar was shorter than 9 cm in all patients. CONCLUSIONS:
      Our work shows that a less invasive approach to many cardiac operations is
      possible through a modified median sternotomy. This technique provides many
      potential and practical advantages: there is less trauma and pain reported by
      patients, and the small wound reduces the risk of infection and blood loss.
      Patients are extubated and discharged from the hospital earlier.

PMID- 9769002
TI  - Arterial graft patency in coronary artery bypass grafting: what do we really
      know?
AB  - BACKGROUND: With increasing use of beating heart techniques for bypass of the
      left anterior descending coronary artery with the left internal mammary artery
      (LIMA), appropriate concerns have been raised of whether graft patency by these
      techniques compares favorably with conventional, arrested heart techniques.
      METHODS: All published articles that examine outcome efficacy of the LIMA graft
      to the left anterior descending coronary artery were reviewed. Because
      angiography has been considered the "gold standard," only those studies that
      included angiographic follow-up were analyzed. RESULTS: From 1972 through 1998,
      there have been 37 peer-reviewed publications that examined outcomes of LIMA
      grafting in conventional coronary bypass grafting, of which 27 contained
      angiographic follow-up data. The completeness of angiographic follow-up was
      variable, but early graft patency (< or =1 month) in studied patients ranged
      between 94% and 99%. Late graft patency (up to 15 years) ranged from 51% to 98%.
      Five recent series of minimally invasive direct coronary artery bypass grafting
      that contained LIMA graft patency data show early graft patency rates between 91%
      and 99%. CONCLUSIONS: Meaningful comparison of LIMA graft patency between
      arrested heart, conventional coronary artery bypass grafting, and minimally
      invasive direct coronary artery bypass grafting is difficult; however, early
      graft patency by both techniques can confidently be stated as being 90% or
      greater.

PMID- 9769003
TI  - Computer-assisted telemanipulation: an enabling technology for endoscopic
      coronary artery bypass.
AB  - BACKGROUND: The ultimate objective of minimally invasive coronary artery bypass
      grafting is to perform the anastomosis totally endoscopically. In this
      feasibility study, we examined the potential of performing coronary artery bypass
      grafting with the use of computer-assisted telemanipulation technology. METHODS:
      Intuitive Telemanipulation Technology (Intuitive Surgical, Mountain View, CA) was
      used to perform an arterial graft to left anterior descending coronary artery
      anastomosis in an ex vivo on-bench swine heart model. The degree of difficulty in
      performing the anastomosis, intraoperative events, duration of the anastomosis,
      and its quality were determined. RESULTS: Anastomosis was performed with relative
      facility, in a range of 10.7 to 17.4 minutes (mean +/- standard deviation, 14.6
      +/- 2.6 minutes). All anastomoses were patent and of good quality except one,
      which had 30% narrowing of its heel. CONCLUSIONS: We conclude that Intuitive
      Telemanipulation Technology may in the future permit the performance of quality
      totally endoscopic coronary artery anastomosis with facility and acceptable time.

PMID- 9769004
TI  - Robotically assisted microsurgery for endoscopic coronary artery bypass grafting.
AB  - BACKGROUND: As minimally invasive approaches to cardiac surgery have expanded, a
      significant number of limitations have become apparent, particularly the lack of
      adequate precision with standard endoscopic instruments. We hypothesized that the
      use of robotics would eliminate some of these limitations. METHODS: Twenty-five
      coronary anastomoses on an isolated porcine heart, using an arterial conduit to
      the left anterior descending artery, were performed endoscopically with a
      microsurgical robotic system. Sophisticated robotic engineering was used to
      control modified endoscopic instruments under direct surgeon control. Computer
      tremor elimination and motion scaling allowed for precise maneuvering. An
      arteriotomy was placed in the left anterior descending artery, and an arterial
      conduit was positioned for anastomosis. The camera and port sites were placed 90
      degrees from the long axis of the arteriotomy. A 7-0 Prolene (Ethicon,
      Somerville, NJ) suture was used to perform the anastomosis in a continuous
      fashion, begun at the 12 o'clock position and continued counterclockwise. After
      completion of half of the anastomosis, the conduits were pulled down and the
      final sutures were placed. The sutures were tied intracorporeally and the
      procedure was completed. RESULTS: The 25 conduits were successfully completed and
      showed good probe patency. Average time for completion of the anastomosis was
      31.7 +/- 2.0 minutes. Appropriate port placement and orientation, and
      stabilization of the conduits were critical. The lack of tremor and motion
      scaling allowed for the precise movements needed to complete an endoscopic
      microvascular anastomosis. CONCLUSIONS: Coronary artery anastomoses are
      technically feasible with use of robotic instrumentation. This technology may
      enable the development of a truly endoscopic approach to bypass surgery.

PMID- 9769006
TI  - Minimally invasive coronary revascularization in elderly patients.
AB  - BACKGROUND: Internal mammary artery to left anterior descending coronary artery
      anastomosis can be done without extracorporeal circulation on the beating heart.
      This method seems to have particular advantages for elderly patients, those 70
      years old or older. METHODS: From January 1, 1997, to October 31, 1997, 27
      patients have been operated on with a minimally invasive approach through a left
      sided minithoracotomy. Twelve patients had up to four previous percutaneous
      interventions with percutaneous transluminal coronary angioplasty (3) or
      percutaneous transluminal coronary angioplasty and stent implantation (9). The
      remainder showed stenosis not suitable for percutaneous transluminal coronary
      angioplasty or an occluded vessel. In all patients the internal mammary artery
      was anastomosed with the left anterior descending coronary artery, and in 2
      patients additionally with the first diagonal. In 1 patient the operation had to
      be converted to a sternotomy because it was impossible to identify the left
      anterior descending coronary artery. RESULTS: All patients survived the
      operation. There was no perioperative infarction. All patients were extubated
      within 4 hours. Mean stay in the intensive care unit was 20.3 hours;
      postoperative stay was 7.4 days. Nine patients had elective repeat angiography
      within 10 days postoperatively and all showed a patent graft. CONCLUSIONS: We
      believe that minimally invasive coronary revascularization of the anterior wall
      can be done in elderly patients with low risk and good results.

PMID- 9769005
TI  - Off-pump multivessel coronary bypass via sternotomy is safe and effective.
AB  - BACKGROUND: In an attempt to avoid the deleterious effects of cardiopulmonary
      bypass, off-pump coronary artery bypass grafting has been rediscovered and
      refined. The purpose of this study was to compare clinical outcomes, length of
      stay, and hospital costs with coronary artery bypass grafting on cardiopulmonary
      bypass. METHODS: Coronary artery bypass was performed on 51 patients without
      cardiopulmonary bypass. Patients were selected on the basis of coronary anatomy,
      with significant stenoses in the left anterior descending, ramus intermedius,
      diagonal, right coronary, acute marginal, or posterior descending territories.
      Outcomes were compared with those of a computer-generated matched control group
      having coronary artery bypass grafting on cardiopulmonary bypass (n = 248) during
      the same time period. RESULTS: No preoperative differences were noted between
      groups. There were no deaths in the off-pump group and a mortality rate of 1.6%
      (4/248) in the control group. There was no incidence of stroke, myocardial
      infarction, or reentry for bleeding among patients in the off-pump group. There
      was a reduction in length of stay by 3 days (p = 0.01), blood transfusions by 50%
      (p = 0.0001), and hospital charges by one third (p = 0.05) in the off-pump group.
      Twenty-six patients had repeat coronary angiography before discharge; 41/43
      grafts were widely patent, 1/43 was totally occluded, and 1/43 was narrowed by
      more than 50%. All internal mammary artery grafts were widely patent.
      CONCLUSIONS: Off-pump multivessel cardiopulmonary bypass grafting is a safe and
      effective means of revascularization for patients with coronary stenoses in the
      anterior or inferior regions, with excellent short-term patency rates and minimal
      morbidity.

PMID- 9769007
TI  - Beating heart operations including hybrid revascularization: initial experiences.
AB  - BACKGROUND: The outcome of patients (n = 45) with coronary one- to three-vessel
      disease undergoing beating heart operations using a recently developed
      stabilizing device was investigated. METHODS: Left internal mammary artery-to
      left anterior descending coronary artery (LIMA-to-LAD) revascularization was
      carried out alone (n = 31) or as hybrid procedure in combination with a balloon
      angioplasty (n = 14). RESULTS: All 45 patients underwent a successful LIMA-to-LAD
      procedure without intraoperative complication during a 21 +/- 8-minute (range, 10
      to 53 minutes) LAD occlusion time. In 14 hybrid procedures a total of 19 stenoses
      including 3 left main stenoses were treated successfully by percutaneous
      transluminal coronary angioplasty and stenting. The postoperative courses were
      uneventful with the exception of two surgical reexplorations necessitated by
      bleeding. No worsening of renal, neurologic, or respiratory functions occurred in
      any patient. In the group having a single LIMA-to-LAD procedure, early
      postoperative coronary angiograms (22 of 31) showed a patent LIMA graft and
      excellent anastomosis; this was also true in 4 patients 12 months after operation
      as shown in angiograms. All patients undergoing hybrid revascularization
      demonstrated a patent LIMA-to-LAD anastomosis; in 1 patient there was a
      dissection in the midlevel of the LIMA, which was stented successfully. The 6
      month follow-up angiograms in 7 of 14 patients revealed open LIMA bypass grafts
      in all patients except 1, who was stented because of dissection. CONCLUSIONS:
      These data indicate that a beating heart operation including hybrid
      revascularization is safe and effective in selected patients with coronary one-
      to three-vessel disease including left main stenosis. This approach may be
      especially advantageous in comparison with conventional coronary artery bypass
      grafting in patients with severe concomitant disease.

PMID- 9769008
TI  - Left ventricular geometry and cardiac function during minimally invasive coronary
      artery bypass grafting.
AB  - BACKGROUND: This investigation was designed to study the changes in function and
      geometry of the left ventricle during two critical steps of minimally invasive
      direct coronary artery bypass procedures: placement of an epicardial stabilizer
      and occlusion of the left anterior descending coronary artery. METHODS: Between
      February 1997 and January 1998, 28 patients underwent bypass grafting with the
      left internal thoracic artery to the left anterior descending coronary artery
      (minimally invasive direct coronary artery bypass technique). Transesophageal
      echocardiography was used for determination of fractional area change and to
      assess left ventricular (LV) diameters in two dimensions and at the apex.
      RESULTS: Placement of the epicardial stabilizer resulted in a small decrease in
      LV end-systolic and end-diastolic dimensions; cardiac function remained
      unchanged. Subsequent occlusion of the left anterior descending coronary artery
      caused a moderate decline in cardiac index and fractional area change, an
      increase in LV diameters, and the development of hypokinetic segments within the
      LV myocardium. CONCLUSIONS: The use of an epicardial stabilizer provides a safe
      and effective means to stabilize the operative field during minimally invasive
      direct coronary artery bypass procedures. Monitoring of LV function by
      transesophageal echocardiography enhances the safety of such procedures and is
      highly recommended.

PMID- 9769009
TI  - Role of graft flow measurement technique in anastomotic quality assessment in
      minimally invasive CABG.
AB  - BACKGROUND: Anastomotic quality is currently the critical issue in minimally
      invasive coronary surgery. Although little is known about its effectiveness,
      surgeons routinely assess grafts intraoperatively using flow probes. This study
      was designed to determine whether mean flow and the pattern of flow tracing in
      internal mammary artery grafts obtained with a transit-time flow probe are
      reliable indicators of anastomotic quality. METHODS: Mongrel dogs (n = 14, 30 to
      35 kg) underwent off-pump left, right, or left and right internal mammary artery
      to left anterior descending artery anastomosis (23 grafts). Moderate to severe
      degrees of stenosis were created at the anastomosis by an additional suture.
      Internal mammary artery graft flow was measured before and after the stenosis was
      created with the left anterior descending artery occluded. Angiography was
      performed at random postoperatively to validate the degree of stenosis. Mean flow
      and flow tracing morphology were compared under various degrees of stenosis.
      RESULTS: There were no significant differences in mean graft flow or the
      morphology of the flow tracing between patent (<15%), mild (<25%), moderate
      (<50%), and moderately severe (<75%) stenosis. However, mean graft flow decreased
      (p < 0.05) with severe stenosis (>75%). CONCLUSIONS: Although differences in mean
      graft flow and graft flow morphology were detectable in anastomoses with severe
      stenosis (>75%), they were indistinguishable in anastomoses with mild (<25%) to
      moderately severe (<75%) stenosis. Flow measurement techniques are valuable tools
      intraoperatively, but surgeons should exercise caution in their interpretation.

PMID- 9769010
TI  - Myocardial damage after minimally invasive coronary artery bypass grafting on the
      beating heart.
AB  - BACKGROUND: In conventional coronary artery bypass grafting, the rate of
      perioperative myocardial infarction is reported in the 2% to 6% range; however,
      significantly higher rates are observed if sensitive myocardial marker proteins
      are used to detect perioperative myocardial damage. For minimally invasive direct
      coronary artery bypass grafting, few data are available concerning myocardial
      marker protein release. METHODS: Fifteen consecutive patients (11 male, 4 female;
      mean age, 59.6 +/- 8.5 years) received minimally invasive direct coronary artery
      bypass grafting procedures via minithoracotomy on the beating heart.
      Electrocardiography and transesophageal and transthoracic echocardiography as
      well as determination of creatine kinase-MB mass concentration and cardiac
      troponin I level were used for ischemic monitoring. RESULTS: One patient had a
      perioperative myocardial infarction according to standard criteria and died
      despite mechanical circulatory support. Determination of cardiac troponin I level
      showed small but definitive ischemic damage in 4 of 9 patients (44%) who
      presented transient ischemic signs intraoperatively or postoperatively. In 2 of
      these 4 patients pathologic findings could be detected on angiographic restudies.
      CONCLUSIONS: Subclinical myocardial injury is a common event in minimally
      invasive coronary artery bypass grafting on the beating heart. Cardiac troponin I
      could serve as an adequate diagnostic tool for diagnosis of perioperative
      myocardial infarction in minimally invasive direct coronary artery bypass
      grafting.

PMID- 9769012
TI  - Minimally invasive valve surgery versus the conventional approach.
AB  - As a result of reports touting the effectiveness of minimally invasive valve
      operations, many cardiovascular surgeons and their patients are beginning to
      believe that smaller incisions are always better. According to its proponents,
      the minimally invasive approach results in less pain, a faster recovery, and a
      more satisfactory cosmetic result. Proponents also believe that the operation can
      be done safely and effectively at a lower cost than traditional surgical
      approaches. This may not be the case, however, and additional prospective studies
      must be done before firm conclusions can be drawn. For example, cardiopulmonary
      bypass, myocardial ischemia, and overall operative times are significantly longer
      (40% or more) for minimally invasive surgical procedures. Morbidity and mortality
      rates do not appear to be decreased, the length of hospital stay varies by only 1
      or 2 days, and patients do not necessarily report less postoperative pain. When
      the conventional technique is used, the operation can be performed precisely and
      expeditiously. Should complications occur, the surgeon will have direct access to
      the heart. The cost of a conventional procedure should not be much more than that
      of a minimally invasive procedure, and in some instances it may even be less
      particularly when the less invasive procedure significantly extends the operating
      room time or requires additional monitors or costly disposables.

PMID- 9769011
TI  - Transit-time flow measurement for detection of early graft failure during
      myocardial revascularization.
AB  - BACKGROUND: A low-flow situation in arterial and venous grafts has been
      associated with high rates of perioperative infarction and mortality. This study
      was designed to look at intraoperative graft flow and resistance in patients with
      coronary artery disease. METHODS: Coronary artery bypass graft flow was measured
      in 46 patients. Transit-time flow was used for coronary flow measurements at rest
      as well as after maximal vasodilation with adenosine infusion. RESULTS: Forty
      three of the 46 patients showed normal internal mammary artery graft flow (>20
      mL/min); 3 patients had no or minimal graft flow. Redoing the graft anastomosis
      in these 3 patients resulted in normalization of graft flow. The mean flow
      increased significantly after correction from 0.5 +/- 0.7 mL/min to 15.7 +/- 9.6
      mL/min (p < 0.02). Conversely, vascular resistance decreased significantly from
      138 +/- 10 to 4.8 +/- 1.8 Ohmv (p < 0.0001), as did the pulsatility index (from
      146.9 +/- 95.7 to 3.4 +/- 1.8; p < 0.001). After correction, coronary flow
      reserve was 2.5 +/- 1.1. CONCLUSIONS: Measurements of intraoperative flow and
      resistance as well as derived variables allow assessment of early graft function
      and thus help prevent graft failure and reduce perioperative infarction. Transit
      time volume flow might be a simple tool for quality control in coronary bypass
      procedures.

PMID- 9769013
TI  - Valve operations through a minimally invasive approach.
AB  - BACKGROUND: We analyzed in-hospital results of 87 patients undergoing minimally
      invasive valvular operations (right parasternal incision through third and fourth
      cartilages). METHODS: Age was 21 to 84 years (mean, 56.2 +/- 16); 45 patients
      (51.7%) were female. Five (5.7%) had a previous valvular operation and 8 (9.2%)
      had severe left ventricular dysfunction. Valve diseases were as follows: aortic
      in 35 patients (40.2%), mitral in 44 (50.5%), double in 5 (5.7%), tricuspid
      regurgitation in 2 (2.2%), and mitral periprosthetic leak in 1 (1.1%). RESULTS:
      Nineteen mitral repairs (21.9%), 22 replacements (25.3%), 1 leak closure (1.1%),
      1 tricuspid repair (1.1%), and 1 replacement (1.1%) were performed. Thirty-one
      patients (35.7%) underwent aortic replacement, 2 (2.3%) aortic decalcification, 1
      (1.1%) subaortic membrane resection, 4 (4.6%) a double-valve procedure, and 5
      (5.7%) a single-valve operation combined with myocardial revascularization. In
      hospital mortality was 5.7% (5 patients). Univariate analysis was significant for
      previous operation, New York Heart Association class IV and severe ventricular
      dysfunction. Multivariate analysis was significant for previous operation and
      severe ventricular dysfunction. Atrial fibrillation (12.6%) was the most frequent
      complication. Postoperative stay was 6.5 +/- 6 days. CONCLUSIONS: The minimally
      invasive approach is a useful technique in valvular surgery. Patients with a
      previous valvular operation, severe ventricular dysfunction, and New York Heart
      Association class IV dyspnea have higher in-hospital mortality.

PMID- 9769014
TI  - "J" incision minimal-access valve operations.
AB  - BACKGROUND: Having used various minimal access incisions in 45 patients and our
      approach of "J" incisions, we wished to evaluate results with the latter
      incision. METHODS: Between January 1997 and September 1997, 33 consecutive
      unselected patients underwent minimal access aortic valve operations (n = 25,
      including 4 composite grafts [1 hemiarch, 1 transaortic MVR], 2 root and valve
      repairs, and 1 double valve replacement), mitral valve operations (n = 6, 4
      repairs, 2 replacements, including 1 maze procedure), or atrial septal defect
      repairs through "J" incisions (n = 2). RESULTS: One patient with preoperative
      severe pulmonary disease died of adult respiratory distress syndrome (3%, 1/33).
      The mean cross-clamp and bypass times were 85.9 minutes and 113.5 minutes,
      although for recent isolated aortic valve replacement operations the mean was 44
      minutes (range, 39 to 51 minutes). Mean operative blood use was 0.33 units, and
      no patient required reoperation for bleeding. The mean time before extubation,
      intensive care unit stay, and postoperative stay were 0.44 days, 0.58 days, and
      4.8 days. No strokes occurred. Mean postoperative pain medication requirements
      were 22.9 mg of morphine and 7.1 oral narcotic doses. CONCLUSIONS: "J" incisions
      are safe alternatives to other incisions, result in good exposure, do not require
      division of the mammary arteries, minimize postoperative pain medication
      requirements, and, with experience, can be performed with acceptable aortic cross
      clamp times.

PMID- 9769015
TI  - Transmyocardial laser as an adjunct to minimally invasive CABG for complete
      myocardial revascularization.
AB  - BACKGROUND: To achieve complete myocardial revascularization in patients with
      diffuse coronary artery disease and patients at high risk if they undergo
      cardiopulmonary bypass such as severe systemic disease or diffuse
      arteriosclerosis of the aorta, we have adopted the technique of combining direct
      coronary artery bypass grafting without cardiopulmonary bypass with
      transmyocardial laser revascularization. METHODS: From April 1995 to September
      1997 this technique was used in 77 patients. Ages ranged from 37 to 85 years with
      a mean of 56 +/- 17 years. Diffuse coronary artery lesions were present in 46
      patients, 10 had severely deranged renal function, 7 had diffuse carotid artery
      lesions, and 7 had aortic arch atheromas. Liver dysfunction was present in 4
      patients and severe obstructive airway disease in 3. The mean left ventricular
      ejection fraction was 0.45 +/- 0.05. Midsternotomy approach was used in 65
      patients and anterior minithoracotomy in 12. Direct coronary artery bypass
      grafting without cardiopulmonary bypass was done to the left anterior descending
      coronary artery or right coronary artery or both. Transmyocardial laser
      revascularization using a 1,000-W CO2 laser machine was performed on the areas
      supplied by ungraftable coronary arteries or even in graftable distal targets in
      the posterolateral or inferior wall in patients who were at high risk if they
      underwent cardiopulmonary bypass. RESULTS: The mean number of vessels bypassed
      was 1.12. One patient died of intractable ventricular arrhythmia in the early
      postoperative phase. Mean follow-up was 16.6 months. At 12 months 89% of the
      patients were angina free. Metabolic stress test demonstrated an average increase
      in exercise tolerance from 5.2 at baseline to 9.7 minutes at 12 months.
      Myocardial thallium scanning done at 3-, 6-, and 12-month intervals
      postoperatively revealed that myocardial perfusion in grafted segments had an
      exponential trend of improvement, and perfusion in transmyocardial laser
      revascularization segments showed a linear trend in the same period with a total
      gain of 28.4%. CONCLUSIONS: Transmyocardial laser revascularization is an
      excellent adjunct to minimally invasive coronary artery bypass grafting to
      achieve complete myocardial revascularization in patients with graftable vessels
      in the anterior wall and ungraftable vessels in the posterior and inferior wall.
      This achieves complete myocardial revascularization without compromising safety
      in patients who are at high risk if they undergo cardiopulmonary bypass. Minimal
      morbidity and mortality in the present series revealed that this procedure is
      safe, and postoperative follow-up of these patients showed significant functional
      improvement as well as an improvement in myocardial perfusion scan.

PMID- 9769016
TI  - Should smart operators mix business and surgery?

PMID- 9769017
TI  - Liposomes as drug delivery system: a strategic approach for the treatment of HIV
      infection.
AB  - As the number of individuals infected with human immunodeficiency virus (HIV) is
      growing dramatically throughout the world, it is important to develop strategies
      to improve the treatment of this deadly disease. It is now well established that
      macrophages play a central role in HIV pathogenesis, acting as reservoirs for
      dissemination of virus throughout the immune system. As liposomes are naturally
      taken up by cells of the mononuclear phagocytic system, liposome-based therapy
      represents a convenient approach to improve the delivery of anti-HIV agents into
      infected cells improving thereby the efficacy of drugs and reducing their adverse
      side-effects. A more specific targeting of HIV-infected cells could also be
      obtained by using liposomes bearing surface attached-antibodies. This review
      details the applications of liposomes as drug carriers for the treatment of AIDS.
      It also gives an overlook of the different strategies that could be explored to
      control the progression of the disease in infected individuals.

PMID- 9769018
TI  - Efficacy, safety and mechanism of cyclodextrins as absorption enhancers in nasal
      delivery of peptide and protein drugs.
AB  - Cyclodextrins are used in nasal drug delivery as absorption enhancing compounds
      to increase the intranasal bioavailability of peptide and protein drugs. The most
      effective cyclodextrins in animal experiments are the methylated derivatives,
      dimethyl-beta-cyclodextrin and randomly methylated beta-cyclodextrin, which are
      active at low concentrations ranging between 2% and 5%. However, large species
      differences between rats, rabbits and humans exist for the nasal absorption
      enhancement by cyclodextrins. Based on toxicological studies of the local effects
      of cyclodextrins on the nasal mucosa dimethyl-beta-cyclodextrin and randomly
      methylated beta-cyclodextrin are considered safe nasal absorption enhancers.
      Their effects were quite similar to controls (physiological saline), but smaller
      than those of the preservative benzalkonium chloride in histological and ciliary
      beat frequency studies. In these studies, and in a study of the release of marker
      compounds after nasal administration, methylated beta-cyclodextrins were less
      toxic than sodium glycocholate, sodium taurodihydrofusidate, laureth-9 and L
      alpha-phosphatidylcholine. Systemic toxicity after nasal cyclodextrin
      administration is not expected, because very low doses of cyclodextrins are
      administered and only very small amounts are absorbed. The mechanism of action of
      cyclodextrins may be explained by their interaction with the nasal epithelial
      membranes and their ability to transiently open tight junctions.

PMID- 9769019
TI  - Molecular weight-dependent paracellular transport of fluorescent model compounds
      induced by palmitoylcarnitine chloride across the human intestinal epithelial
      cell line Caco-2.
AB  - Long-chain acylcarnitines, such as palmitoylcarnitine chloride (PCC), are
      endogenous compounds which have been shown to increase intestinal transport of
      small hydrophilic compounds (including some pharmaceutical agents) through the
      paracellular pathway. However, the size range of the compounds whose absorption
      can be improved by PCC has not been fully investigated. In the present study, we
      systematically examined the effect of PCC on the transport rate of a series of
      hydrophilic fluorescent model compounds of varying molecular weights (0.3-71.2
      kD) across cultured monolayers of the human intestinal epithelial cells Caco-2.
      Mucosal addition of 100 or 200 microM PCC resulted in comparable time-dependent
      decreases in the transepithelial electric resistance (T1/2, approximately 15
      min). PCC addition induced a striking increase in the transport of sodium
      fluorescein (Flu-Na; 0.3 kD) and a slight or moderate increase in transports of
      fluorescent compounds of 0.6-11 kD. The effect of PCC on transport of compounds
      with molecular weights of > or = 17 kD appeared to be negligible. Examination by
      confocal laser scanning microscopy clearly revealed dilated paracellular spaces
      in Caco-2 monolayers which had been mucosally pretreated with PCC, confirming
      that PCC increases intestinal permeability by opening a paracellular transport
      pathway. Our results suggest that PCC is particularly effective in enhancing
      intestinal absorption of small hydrophilic compound like Flu-Na and may also have
      limited use in promoting the transport of compounds of < or = 10 kD.

PMID- 9769020
TI  - Disulfide cross-linked Fab-aggregates: preparation and biodistribution.
AB  - The high-molecular-weight soluble aggregates of Fab fragments of murine
      antibodies against cardiac myosin were prepared as a potential long-circulating
      and low immunogenic pharmaceutical carriers by conjugation of thiolated Fab and
      Fab modified with succinimidyl 3-(2-pyridyldithio)propionate. The clearance time
      and biodistribution of 111In-radiolabeled aggregates were studied in normal and
      nude-mice bearing human breast tumor implant and in rabbits with experimental
      myocardial infarction. The aggregates had a prolonged circulation time (half
      clearance time ca. 3-5 h) and ability to concentrate in the tumor and in the
      necrotic area of infarcted myocardium. Similar tumor-to-normal and infarct-to
      normal accumulation ratios (ca. 3 h in both cases) suggest that combination of
      long circulation with impaired filtration in necrotic tissues is responsible for
      this accumulation rather than a specific interaction. The aggregates prepared may
      serve as long-circulating drug carriers able to deliver pharmaceuticals into
      areas with affected and leaky vasculature.

PMID- 9769021
TI  - Production and characterization of fusion proteins containing transferrin and
      nerve growth factor.
AB  - To explore the ability to use genetic fusions of transferrin as a carrier for
      brain targeting and delivery, a series of fusion proteins containing both human
      nerve growth factor (NGF) and human transferrin was produced in mammalian cells.
      A protein in which the hinge region from human IgG3 joined the carboxyl terminus
      of NGF and the amino terminus of transferrin formed a covalent homodimer, bound
      human transferrin receptor, and retained full NGF in PC12 cells. In contrast,
      proteins in which polypeptide dimerization was not induced or in which NGF was
      fused through its amino terminus had greatly reduced NGF activity. The ability to
      maintain both biologically active NGF and transferrin as part of a fusion protein
      may offer a novel way to deliver NGF and other neurotrophic factors to the
      central nervous system.

PMID- 9769022
TI  - QSAR analysis of polyamine transport inhibitors in L1210 cells.
AB  - PURPOSE: In this paper, the authors attempt to construct a mathematical model to
      correlate the biological activities of 63 polyamine transport inhibitors in L1210
      cells with their physicochemical parameters. METHOD: The inhibitory constants
      (Ki) were obtained from the published work of Bergeron et al. Non-weighted least
      square method was used in deriving the regression equations with a BMDP program.
      An AM1 subroutine of the HyperChem program was used to optimize the geometry and
      calculate the molecular dipole moments and the distance between two terminal
      amino groups. A CQSAR program was used to calculate Clog P (oct./w.). RESULTS: A
      good correlation (r2 = 0.81) was obtained by using a five-parameter equation
      including the distance between two terminal amino groups (d), the number of
      cationic charge (Charge), molecular weight (MW), dipole moment (mu), and hydrogen
      bond forming ability (Hb). CONCLUSION: This model accounts for 81% of the
      variance in the data and can be used to estimate transport-inhibitory activity of
      many other polyamine analogues. It gives some quantitative information about the
      relationship between the polyamine analogues' function as transport inhibitors
      and their molecular structures.

PMID- 9769023
TI  - Glial cell reactions in neurodegenerative diseases: pathophysiology and
      therapeutic interventions.
AB  - A variety of proteins known to be involved in inflammatory processes are
      associated with lesions in chronic neurodegenerative disorders such as Alzheimer
      disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS).
      This is particularly true of AD, in which inflammatory reactions are believed to
      be important contributors to the neuronal loss. Inflammatory proteins associated
      with AD include complement proteins, complement inhibitors, acute-phase
      reactants, inflammatory cytokines, proteases, and protease inhibitors. Studies of
      cultured human astrocytes and microglia obtained from postmortem brain have
      established that almost all of these proteins are produced by one or the other of
      these two cell types. Human neurons also produce many inflammatory proteins and
      their inhibitors, creating complex interactions. Accumulations of amyloid,
      extracellular tangles, or Lewy bodies apparently act as irritants, causing the
      activation of complement, the initiation of reactive changes in microglia, and
      the release of potentially neurotoxic products such as the membrane attack
      complex, oxygen free radicals, and excess glutamate. A number of epidemiologic
      studies indicate that populations taking anti-inflammatory drugs have a sharply
      reduced prevalence of AD. One small clinical trial with indomethacin showed
      arrest of the disease over a 6-month period. Therapeutic intervention in key
      inflammatory processes holds great promise for the amelioration of AD and
      possibly other neurodegenerative disorders.

PMID- 9769024
TI  - A strategy for identifying immunosuppressive therapies for Alzheimer disease.
AB  - There is increasing evidence that the immune system plays an important role in
      the pathology of Alzheimer disease (AD). The fundamental steps in this process
      involve induction of neurotoxic microglia by senile plaques. Recent studies have
      shown that microglia in contact with isolated plaque fragments secrete
      neurotoxins that can cause neuronal injury and brain damage typical of AD. In
      vitro models help to delineate individual steps of this activation cascade by
      which quiescent microglia become neuron-killing cells. Moreover, such model
      systems provide rapid screening assays to identify immunosuppressive drugs that
      might slow brain damage brought on by neurotoxic microglia.

PMID- 9769025
TI  - Properties of activated microglia and pharmacologic interference by
      propentofylline.
AB  - Ameboid microglia are activated macrophages in the developing brain. With age,
      these cells undergo gradual transformation into the adult form, known as ramified
      or resting microglia. In response to neuronal insults, microglia change their
      morphology and immunophenotype and proliferate to become full-blown brain
      macrophages. Microglia release a battery of neurotoxic substances. Responses to
      neuronal damage occur at various intervals after the insult, suggesting that
      microglia may be an attractive target for pharmacologic intervention. The
      cerebrospinal fluid (CSF) of Alzheimer disease (AD) patients contains antibodies
      that recognize activated microglia in the developing rat and in the ischemic
      gerbil brain. These results suggest that AD shares common mechanisms related to
      the activation of microglia with both these experimental models. In vitro, the
      xanthine derivative propentofylline (PPF) depresses the production of reactive
      oxygen intermediates produced by macrophages. To appreciate in vivo interactions
      of PPF, two models were employed: developing rats and adult gerbils exposed to
      ischemia. Newborn rats were administered PPF (10 mg/kg) for 7 days. Gerbils were
      exposed to 5 min of transient forebrain ischemia and received PPF (10 mg/kg) 24 h
      later until the day before sacrifice. Animals were sacrificed at 7 or 14 days
      after reperfusion. Brains were processed for immunocytochemistry. Reactive
      microglia were visualized with monoclonal antibodies OX18 and OX42 or AD-CSF
      microglia antibodies. In the case of ischemia, an antibody against the amyloid
      precursor protein (APP) (residues 676-695) was included. Newborn rats receiving
      PPF for 7 days displayed a dramatic reduction in the number of activated
      microglia compared with untreated littermates. Ischemic control in gerbils showed
      complete nerve death, accumulations of APP, and enhanced microglial reactivity.
      In gerbils receiving PPF, APP accumulation was absent or very slight, and
      activated microglia were downregulated. The ability of PPF to interfere with
      activated microglia suggests that this agent may be useful for slowing
      progressive nerve cell death associated with AD, which is considered to be
      largely influenced by pathologic glial reactions.

PMID- 9769026
TI  - Interfering with the pathologic activation of microglial cells and astrocytes in
      dementia.
AB  - Cascading glial cell activation is believed to play an essential pathogenic role
      in the development of dementia. Reactive microglia may contribute to neuronal
      damage by the generation of free oxygen radicals and nitric oxide (NO), which
      forms the particularly aggressive peroxynitrites, and by the release of
      potentially neurotoxic cytokines such as tumor necrosis factor-alpha (TNF-alpha).
      The pathologically stimulated release of interleukin-1beta (IL-1beta) from
      microglial cells triggers secondary activation of astrocytes, which are forced to
      proliferate and to give up their differentiated state. As a consequence,
      physiologically required astrocyte functions may be impaired, such as uptake of
      glutamate and K+ from the extracellular space and release of neurotrophic
      factors. At the same time, production of inflammatory proteins which, for
      example, promote the formation of toxic beta-amyloids, is reported to be
      stimulated in reactive astrocytes. Because the complex molecular signaling that
      controls glial cell activation is only beginning to be elaborated, we attempted
      to elucidate the role that has been adopted during evolution by the endogenous
      cell modulator adenosine. This nucleoside exerts a homeostatic effect on reactive
      glial cell functions by a sophisticated control of the second messenger
      interplay, counteracting a pathologically induced dysbalance of the Ca2+- and
      cAMP-dependent signaling. A strengthening of the cAMP-dependent signaling chains
      was found to counteract the proliferation rate, the formation of free oxygen
      radicals, and the stimulated release of TNF-alpha and IL-1beta in cultivated
      microglia. It also helped proliferative astrocytes to regain their differentiated
      state and a mature ion channel pattern. The cAMP-linked homeostatic adenosine
      effects could be reinforced or mimicked by propentofylline, a pharmacon that
      raises the effective extracellular concentration of adenosine by inhibiting its
      cellular reuptake and increases the cellular cyclic nucleotide content by
      selective phosphodiesterase inhibition. We conclude that a pharmacologically
      reinforced homeostatic control of the pathologically altered Ca2+/cAMP crosstalk
      may prevent glia-related neuronal damage, providing a potential option for the
      treatment of dementia.

PMID- 9769027
TI  - Propentofylline in the treatment of vascular dementia and Alzheimer-type
      dementia: overview of phase I and phase II clinical trials.
AB  - Pathophysiologic processes common to both vascular (multi-infarct) dementia and
      dementia of the Alzheimer type may include microglial activation with resultant
      generation of inflammatory cytokines and neurotoxic free radicals, decreased
      secretion of nerve growth factor by astrocytes, excess release of glutamate with
      associated neurotoxicity, and loss of cholinergic neurons. The functional
      benefits and neuroprotective effects of propentofylline (PPF) stem from its
      interference with these overlapping pathways of neurodegeneration. The clinical
      pharmacology and safety of PPF were studied in a number of phase I studies in
      healthy young and elderly adults and in patients with renal or hepatic
      impairment. These studies have shown that PPF 300 mg t.i.d. is safe and well
      tolerated when taken on an empty stomach 1 h before meals. In a randomized,
      double-blind phase II study involving 190 elderly subjects with clinically and
      psychometrically documented mild to moderate dementia, 12 weeks of PPF therapy
      produced significantly greater improvements than placebo in Gottfries-Brane-Steen
      (GBS) scores, Mini-Mental State Examination (MMSE) scores, and Clinical Global
      Impression (CGI) ratings. A subsequent phase II study using positron emission
      tomography (PET) revealed that cortical glucose metabolism improved significantly
      in patients with vascular dementia after 12 weeks of PPF treatment but
      deteriorated significantly with placebo. A third phase II study, which enrolled
      patients with Alzheimer-type dementia, demonstrated that PPF significantly
      enhanced functional reserve, as reflected by increases in regional cerebral
      glucose metabolism after stimulation with a verbal memory task. In contrast,
      patients randomized to placebo exhibited a significant decline in functional
      activation and significant worsening in their MMSE scores over the course of this
      12-week study. Propentofylline proved to be safe, well tolerated, and free of
      severe side effects in all three of these phase II trials. Phase I trial results
      suggest that significant food interactions occur with PPF, indicating that the
      drug should be taken on an empty stomach 1 h before meals. Phase II trial results
      indicate that PPF yields clinically measurable improvements in the symptoms of
      dementia and prevents loss of stimulation-related increases in glucose metabolism
      over a treatment period of 3 months. Whether these results indicate that PPF can
      slow the progression of dementia can be determined only by long-term trials
      specifically designed to determine the drug's effect on disease progression.

PMID- 9769028
TI  - The trophic effects of purines and purinergic signaling in pathologic reactions
      of astrocytes.
AB  - This article reviews the effects of extracellular purine bases, nucleosides, and
      nucleotides as intracellular signaling molecules with trophic effects on cells
      after insults to the brain and spinal cord. Astrocytes are the principal source
      of extracellular purines in brain after injury, ischemia, or trauma. In vitro and
      in vivo extracellular purines have both immediate and long-term trophic effects,
      including stimulation of astrocyte and neuronal differentiation, mitosis,
      morphogenesis, apoptosis, and stimulation of growth and trophic factor synthesis.
      The effects of the nucleoside adenosine and the nucleotide adenosine triphosphate
      (ATP) are mediated principally via specific receptors on the cell surface coupled
      to a series of signaling cascades. Unlike adenosine and ATP, guanosine and
      guanosine triphosphate (GTP) do not act at classical purine receptors. However,
      they exert similar effects on astrocytes, apparently by causing the astrocytes to
      release large amounts of adenosine and ATP over prolonged periods. The release of
      adenosine and ATP may be related to the effects of guanosine on the purine
      nucleoside transporters in the cell membrane, whereas the release of ATP may be
      due to the effects of GTP on the ATP-binding cassette (ABC) proteins.
      Physiologically, the effects of guanosine are important because this nucleoside,
      unlike adenosine, remains elevated for prolonged periods after brain injury.

PMID- 9769029
TI  - Current concepts in joint replacement.

PMID- 9769030
TI  - Millennium arthroplasty: materials, methods, & mechanisms.

PMID- 9769031
TI  - Factors influencing polyethylene wear in total joint arthroplasty.

PMID- 9769032
TI  - The clinical picture of debris generation: map reading.

PMID- 9769033
TI  - Osteolysis: dealing with the consequences.

PMID- 9769034
TI  - Porous-coated total hip arthroplasty in the young.

PMID- 9769035
TI  - Hydroxyapatite: catalyst or conjurer?

PMID- 9769036
TI  - Femoral fixation algorithm for what works.

PMID- 9769037
TI  - The cemented all-polyethylene acetabular total hip arthroplasty.

PMID- 9769038
TI  - The acetabular component: an elliptical monoblock alternative.

PMID- 9769039
TI  - Hip arthroscopy for acetabular dysplasia: a pipe dream?

PMID- 9769040
TI  - Nerve injury in the prosthetic management of the dysplastic hip.

PMID- 9769041
TI  - Periprosthetic fractures associated with total hip arthroplasty.

PMID- 9769042
TI  - Blood conservation in total joint arthroplasty.

PMID- 9769043
TI  - Reconstruction at a high hip center in acetabular revision surgery using a
      cementless acetabular component.

PMID- 9769044
TI  - Distal fixation with fully coated stems in femoral revision: a 16-year follow-up.

PMID- 9769045
TI  - Proximal femoral allografts for reconstruction of bone stock in revision hip
      arthroplasty.

PMID- 9769046
TI  - Acetabular revision options.

PMID- 9769047
TI  - Back to the future: evolution in hip design.

PMID- 9769048
TI  - A femoral component for hip replacement.

PMID- 9769049
TI  - Calcium sulfate bone-void filler.

PMID- 9769050
TI  - Adventures in mobile-bearing knee design: a mid-life crisis.

PMID- 9769051
TI  - DVT prophylaxis options: facts & fictions.

PMID- 9769052
TI  - Mobile-bearing joint replacement options in post-traumatic arthritis of the knee.

PMID- 9769053
TI  - Putting it all together: the importance of the trial reduction in total knee
      replacements.

PMID- 9769054
TI  - Alternative surveillance after total knee arthroplasty: a viable option?

PMID- 9769055
TI  - Repairing minor bone defects: augmentation & autograft.
AB  - Numerous options exist for management of minor bone defects associated with TKA.
      Biomechanical data demonstrate that filling defects with methylmethacrylate, with
      or without screw augmentation, results in inferior load transfer. Rectangular
      augmentations may be superior to angular wedges due to reduction in shear
      stresses. Controversy persists regarding superiority of use of bone graft versus
      augmentation. The author favors bone graft for cavitary defects, massive bone
      loss, and in younger patients in whom additional revision surgery is likely.
      Prosthetic augmentation is favored in peripheral defects of moderate size in more
      elderly patients.

PMID- 9769056
TI  - Morselized allografting in revision total knee arthroplasty.

PMID- 9769057
TI  - Structural bone grafting about the knee.

PMID- 9769058
TI  - Management of extensor mechanism complications.

PMID- 9769059
TI  - Periprosthetic fractures following total knee arthroplasty: the good, bad, &
      ugly.

PMID- 9769060
TI  - Common litigation problems: dueling with the devil.

PMID- 9769061
TI  - Cost reduction in total joint arthroplasty.

PMID- 9769062
TI  - Hip challenges: what would you do?

PMID- 9769063
TI  - Knee challenges: what would you do?

PMID- 9769064
TI  - Normal plasma lactose concentrations and kinetics of intravenously infused
      lactose in cattle.
AB  - Plasma lactose concentration and its kinetics were determined in apparently
      normal cattle, as a prelude to investigating its chemotherapeutic significance in
      bovine trypanosomiasis. It is hoped that intravenously administered lactose may
      be able to reduce the rate of sequestration of desialylated erythrocytes during
      Trypanosoma vivax infection of cattle; thus decreasing the rate of development of
      trypanosomal anaemia in infected animals. A range of 0.061 to 0.55 mM with a mean
      of 0.208 +/- 0.128 mM standard deviation (SD), observed in adult cattle was
      significantly lower (P<0.001) than corresponding values in recently weaned
      calves; 0.429 to 1.496 mM (0.972 +/- 0.318 mM). Semi-logarithmic plots from
      calves given a single dose (0.5 g lactose per kg bodyweight as a solution in
      normal saline, infused at the rate of 18 ml min(-1)) showed a biexponential
      pattern of regression lines. Decrease in plasma concentrations was biphasic and
      lactose was rapidly distributed into the extravascular space after
      administration. The biological half-life (t1/2) of the infused lactose ranged
      from 4.10 to 6.00 hours (5.01 +/- 0.81 hours); its mean elimination rate constant
      was 0.14 +/- 0.02 hour(-1), mean apparent volume of distribution was 168.09 +/-
      56.65 ml kg(-1) while its mean total clearance was 23.54 +/- 8.31 ml kg(-1) hour(
      1). A single dose rapidly reached a peak and gradually fell below the pre
      infusion level while repeated doses did not cause accumulation of the lactose in
      the plasma as each infusion fell back to normal relatively rapidly.

PMID- 9769065
TI  - Ricobendazole kinetics and availability following subcutaneous administration of
      a novel injectable formulation to calves.
AB  - The plasma and abomasal fluid disposition kinetics of ricobendazole (RBZ) after
      subcutaneous (s.c.) administration of a novel injectable formulation to calves,
      and the comparative plasma availability after s.c. injection of RBZ and that
      obtained after oral treatment with albendazole (ABZ), were characterised. Six
      parasite-free Holstein calves received RBZ (solution 150 mg ml(-1)) by s.c.
      injection at 3.75 mg kg(-1) (Experiment 1). Experiment 2 was conducted in two
      experimental phases; in phase I, five calves (Group A) received RBZ by s.c.
      injection and five animals (Group B) were orally treated with ABZ (suspension 100
      mg ml(-1)), at 5 mg kg(-1). Drug treatments were reversed for each group in phase
      II and given at 7.5 mg kg(-1). Samples of abomasal fluid (via cannula) and
      jugular blood were collected over 72 hours post-treatment and analysed by HPLC.
      RBZ and its sulphone metabolite were detected in plasma following its s.c.
      administration. RBZ was rapidly absorbed, reaching the plasma Cmax at 4.5 hours
      post-dosing. The sulphone metabolite followed a similar kinetic pattern. Both
      molecules were rapidly and extensively distributed into the abomasum, being
      detected in abomasal fluid between 30 minutes and 36 hours post-administration.
      An extensive plasma/abomasum exchange process, with ionic-trapping in the
      abomasum, accounted for the higher AUC value (>200 per cent) obtained for RBZ in
      abomasum compared with plasma. The s.c. treatment with RBZ formulated as a
      solution resulted in a significantly greater plasma availability (measured as ABZ
      sulphoxide) than the oral treatment with ABZ (suspension) given at the same dose
      rates.

PMID- 9769066
TI  - Detection of avian reovirus RNA and comparison of a portion of genome segment S3
      by polymerase chain reaction and restriction enzyme fragment length polymorphism.
AB  - A reverse transcription-polymerase chain reaction (RT-PCR) was established to
      amplify a 672-base pairs fragment on the segment S3 of avian reovirus (ARV). The
      amplified fragments were detected in nine strains of ARV as well as three tendon
      tissue specimens, indicating that the primer regions were well conserved. The RT
      PCR was able to detect as low as 0.2 pg using an ethidium bromide stained gel.
      The detection limit could be enhanced further to 0.04 pg by hybridisation after
      southern transfer. The amplified DNA fragments from nine ARV strains and two
      tissue specimens showed different restriction enzyme cleavage patterns. Analysis
      of the data revealed that these 11 strains were classified into four groups. The
      results suggest that PCR followed by restriction enzyme analysis may provide a
      simple and rapid method for the characterisation of ARV isolates.

PMID- 9769067
TI  - CT-assisted versus silicone rubber cast morphometry of the lower respiratory
      tract in healthy amazons (genus Amazona) and grey parrots (genus Psittacus).
AB  - The objective of this study was to examine the normal respiratory tract of grey
      parrots and amazons by using two different methods. The lower respiratory tract
      of five amazons and four grey parrots, all healthy, were investigated applying
      computerised tomography (CT). Volumes and densities of the body, the body
      cavities, the normal lungs, and the airsacs in the living animals were defined as
      reference values of healthy birds to give a basis for future CT-diagnosis of
      respiratory diseases and their precise locations in parrots. In a parallel study,
      the lung and air sac volumes of six amazons and two grey parrots were measured
      using silicone rubber casts produced after the method described by H.-R. Duncker.
      Values for identical respiratory structures gained by these different methods
      were compared.

PMID- 9769069
TI  - Comparative development of antitrochanteric disease in male and female turkeys of
      a traditional line and a contemporary sire-line fed ad libitum or with restricted
      quantities of food.
AB  - The prevalence of musculoskeletal disease at eight, 16, 24, 34, 44 and 54 weeks
      of age in male and female turkeys was determined by dissecting 688 limbs from
      traditional lines and sire-line turkeys fed to achieve different bodyweights.
      Traditional turkeys were fed ad libitum and sire-line turkeys were fed ad libitum
      or restricted to 0.5 during rearing and subsequently to 0.8 of ad libitum-fed
      bodyweight of birds of the same strain and sex. A group of male sire-line turkeys
      was also fed ad libitum to 18 weeks and 0.8 of ad libitum thereafter. Lameness
      during the rearing period was usually associated with joint infection. Ruptured
      ligaments were an occasional finding in sire-line turkeys before sexual maturity.
      The major finding at 34, 44 and 54 weeks of age was degeneration of the
      antitrochanter in both sexes of the sire-line. The prevalence and severity of
      disease increased with age but was not generally associated with lameness.
      Antitrochanteric degeneration in the sire-line was diminished by decreasing
      bodyweight through food restriction. Antitrochanteric degeneration did not occur
      in traditional turkeys.

PMID- 9769068
TI  - Intestinal permeability of Irish setter puppies challenged with a controlled oral
      dose of gluten.
AB  - A combined test of intestinal permeability using lactulose (L) and rhamnose (R),
      and absorptive function using xylose (X) and 3-O-methylglucose (G), was carried
      out at four, six, eight and 16 weeks of age in 22 healthy control and six gluten
      sensitive Irish setter (IS) dogs fed a diet containing a controlled dose of
      gluten from weaning. Comparisons were made with two groups of 12 healthy control
      dogs of breeds other than IS, one fed the same diet as the setters and the other
      fed a gluten-free diet. Gluten-sensitive IS showed a rise in permeability (mean
      [SEM] urinary L/R) from 0.23 (0.07) at four weeks to 0.39 (0.05) at eight weeks,
      remaining at 0.36 (0.04) at 16 weeks. These results were significantly higher in
      gluten-sensitive than control IS at six, eight and 16 weeks, compatible with
      jejunal biopsy lesions characteristic of gluten-sensitive enteropathy
      demonstrated in affected dogs at 16 weeks. Urinary L/R ratios of control dogs of
      breeds other than IS peaked at six weeks 0.27 (0.02), and were significantly
      higher than those of control IS at six and eight weeks, demonstrating differences
      in permeability between Irish setter dogs and other breeds at this age. There
      were no significant differences in urinary X/G ratios at six, eight and 16 weeks
      of age between any of the groups of dogs challenged with gluten. Urinary L/R and
      X/G ratios were similar in the control dogs of breeds other than IS fed gluten
      containing and gluten-free diets. These findings indicate that intestinal
      permeability testing of puppies during controlled oral gluten challenge provides
      a practical screening test for gluten sensitivity in Irish setter dogs at an
      early age.

PMID- 9769070
TI  - Investigation of the cellular tropism of bovine immunodeficiency-like virus.
AB  - Bovine immunodeficiency-like virus (BIV) was first isolated from an animal
      showing transient leucocytosis, lymphadenopathy, lesions in the central nervous
      system and progressive weakness and emaciation. Similar signs are observed in
      other immunosuppressive lentiviral infections. BIV, like other lentiviruses, has
      been isolated from peripheral blood mononuclear cells and lymphoid tissue of
      infected animals. However, the in vivo cellular tropism of BIV remains unclear
      although initial studies indicate that BIV may be pantropic, infecting T cells, B
      cells and monocytes similar to some of the immunodeficiency-causing lentiviruses.
      PCR, Southern blot hybridisation, cell culture and reverse transcriptase assays
      were used to demonstrate the presence of BIV proviral DNA and the production of
      infectious virus in CD2+, WC1+, B cells and monocytes during the acute stages of
      infection. Western immunoblot assays were used to assess the development of
      antibody responses towards the virus.

PMID- 9769071
TI  - Effects of hypercapnia on endocrine and metabolic responses to anaesthesia in
      ponies.
AB  - Some metabolic and endocrine effects of hypercapnia were studied in six ponies
      during halothane anaesthesia with neuromuscular blockade and controlled
      ventilation. Each was anaesthetised twice, once with a 40-minute-period of
      hypercapnia (10 kPa) and once when normocapnia (5.3 kPa) was maintained
      throughout two hour's anaesthesia. Routine cardiovascular monitoring was
      performed and blood samples were taken for assay of cortisol, insulin, glucose,
      lactate, muscle and liver enzymes and total protein. Anaesthesia induced
      hypotension and lacticacidaemia which were slightly ameliorated during
      hypercapnia. Hyperglycaemia was more marked during hypercapnia. Plasma cortisol
      increased in a similar manner in both groups and insulin tended to decrease.
      There were no major changes in the other variables measured. It was concluded
      that 40 minutes of hypercapnia during halothane anaesthesia in ponies may have
      improved perfusion and did not markedly alter the stress response.

PMID- 9769072
TI  - Breath hydrogen measurement in ponies: a preliminary study.
AB  - The aim of this study was to establish the normal patterns of breath hydrogen
      excretion in adult ponies following either voluntary consumption or
      administration per stomach tube of a test meal/carbohydrate substrate. After an
      overnight fast, the ponies (n = 7) received either no test meal (ie fasted),
      glucose, xylose, lactose, lactulose, wheat flour or oats. Exhaled breath samples
      were collected in duplicate at 0 minutes and at 30-minute intervals thereafter
      for eight hours. Analysis of duplicate breath hydrogen measurements (n = 714)
      indicated that the breath hydrogen collection/storage method was reliable.
      Fasting resulted in negligible levels of breath hydrogen excretion. Increases in
      breath hydrogen concentration greater than 10 ppm, sustained for at least 30
      minutes, were regarded as being biologically significantly different than fasting
      data and were observed for all ponies following the ingestion of oats or the
      administration of wheat flour, for three ponies following the administration of
      glucose and xylose and for two ponies following the administration of lactulose
      and lactose. The pattern of breath hydrogen excretion was subject to variation
      between animals following the ingestion of identical test meals. This study
      provides evidence of incomplete glucose absorption in healthy ponies and
      indicates that ingestion of non-absorbable carbohydrates do not always result in
      hydrogen excretion.

PMID- 9769073
TI  - The accuracy and reliability of linear measurements of the ulna for
      anthropometrical studies in dogs.
AB  - This study investigated the accuracy and reliability of measuring the distance
      between two surface landmarks (the point of the tuber olecrani and the proximal
      aspect of the stopper pad) as an indication of ulna length in the live dog. It
      was found that the chosen skin landmarks did correlate well with the length of
      the ulna bone. The reliability of such measurements was high when performed by a
      single person, however this fell to unacceptable levels when multiple people were
      used to make the measurements. It was concluded that if this technique was to be
      used in studies to serially record the bone length in live growing dogs, then the
      measurements should be taken by a single person.

PMID- 9769074
TI  - Evaluation of B and T lymphocytes and plasma cells in colonic mucosa from healthy
      dogs and from dogs with inflammatory bowel disease.
AB  - The aim of this study was to investigate the subpopulations of lymphocytes in the
      colonic mucosa of healthy dogs and dogs with inflammatory bowel disease (IBD).
      Fourteen normal dogs and 13 dogs with IBD were examined. Endoscopic biopsy
      specimens of colonic mucosa from each dog were stained specifically for pan T
      lymphocytes (CD3) and pan B lymphocytes (CD79a), and for plasma cells with methyl
      green pyronin (MGP) stain. Cells were counted by means of a grid and statistical
      analysis was performed on the data collected. B and T lymphocytes were also
      counted in the glandular epithelium of normal dogs and dogs with IBD and the
      normal and abnormal groups compared statistically. Healthy dogs had significantly
      lower numbers of T cells in the lamina propria and glandular epithelium and
      significantly lower numbers of B cells in the lamina propria. Significant group
      differences for plasma cells were not evident. Our results indicate that in IBD a
      chronic cellular immune reaction is present in the diseased gut involving
      increased numbers of B and T lymphocytes.

PMID- 9769075
TI  - Effects of Trypanosoma congolense and nutritional supplements in Djallonke ewes
      on live weight during pregnancy, post partum weight, haematology parameters and
      lamb performance.
AB  - The effects of Trypanosoma congolense infection and nutritional supplements on
      live weight changes during pregnancy, haematology traits and offspring
      performance were studied in 42 Djallonke ewes. A randomised block design was used
      to allocate ewes to four treatment combinations, of which two were on a
      restricted diet (L) and the remainder on an unrestricted diet (H). Half of each
      nutritional group were infected with T congolense (LI, HI), the remainder serving
      as controls (LC, HC). The degree of anaemia following infection was similar in
      both infection groups (P<0.0001), but the erythropoietic activity, as judged by
      the increase in mean corpuscular volume, was significantly greater in the HI
      group (P<0.01). Live weight gains during pregnancy attributable to higher
      supplements were significantly depressed by infection (P<0.01). Post partum
      weight was lower in the LI group as compared with the LC control. Diet interacted
      significantly (P<0.01) with infection and resulted in the lowest lamb growth
      rates in the LI group. It was concluded that dietary supplementation of
      trypanosome-infected Djallonke ewes during pregnancy and lactation improves
      productivity in terms of ewe live weight and improved lamb growth rates to
      weaning.

PMID- 9769076
TI  - Impairment of gas exchange due to alveolar oedema during xylazine sedation in
      sheep; absence of a free radical mediated inflammatory mechanism.
AB  - We studied the mechanism of impairment of gas exchange following sedation with
      the alpha2 adrenoreceptor agonist, xylazine, in Suffolk cross-bred sheep
      spontaneously breathing room air. Xylazine caused a significant fall in PaO2 from
      a mean (pre-xylazine) of 97.9 mm Hg (6.7 mm Hg SEM) to a mean of 38.1 mm Hg (3.2
      mm Hg SEM) one minute after injection with a transient increase in PaCO2 from a
      mean (pre-xylazine) of 32.6 mm Hg (1.9 mm Hg SEM) to a mean of 40.2 mm Hg (3.0 mm
      Hg SEM). There was no significant fall in mean arterial pressure or in white cell
      count. There was no significant change in a number of indices of free radical
      release which included ascorbyl radical, plasma antioxidant potential and alpha
      tert-butyl phenyl nitrone (PBN) spin adduct measured simultaneously in both
      arterial and venous blood. In all sheep given xylazine there was no histological
      evidence of platelet emboli but lung histopathology showed evidence of pulmonary
      oedema and intense microvascular congestion with red cells extravasated into
      alveoli. No such histological changes were seen in the lungs of normal sheep. The
      impaired gas exchange during sedation with xylazine in sheep is caused, not by an
      oxidant mediated inflammatory mechanism or by platelet emboli, but by intense
      alveolar oedema which is probably due to pulmonary venospasm.

PMID- 9769077
TI  - Pharmacokinetics of amoxicillin/clavulanic acid combination after intravenous and
      intramuscular administration to pigeons.
AB  - The pharmacokinetics of amoxicillin/clavulanic acid (4:1) combination were
      studied after intravenous and intramuscular administration of single doses (25 mg
      kg(-1) bodyweight) to 50 pigeons. The plasma concentrations-time data were
      analysed by compartmental pharmacokinetics and non-compartmental methods. The
      disposition curves for both drugs after intravenous administration were best
      described by a two-compartment open model. The apparent volumes of distribution
      of amoxicillin and clavulanic acid were 1.77 litres kg(-1) and 1.30 litres kg(-1)
      respectively. The body clearances of amoxicillin and clavulanic acid were not
      significantly different. The elimination half-lives of amoxicillin after
      intravenous and intramuscular administration were 1.22 (0.09) hour and 1.52
      (0.09) hour respectively, and those of clavulanic acid were 1.15 (0.08) hour and
      1.49 (0.08) hour. After intramuscular administration both drugs had a
      significantly longer half-life (P<0.05) than that after the intravenous
      treatment. The bioavailability after the intramuscular injection was high and
      similar for both drugs (75.98 per cent for amoxicillin and 74.61 per cent for
      clavulanic acid). The mean peak plasma concentration of clavulanic acid (0.29
      hour) was reached earlier than amoxicillin (0.38 hour) and peak concentrations
      were proportional to the dose of both products administered (5.81 mg litre(-1) of
      amoxicillin and 1.89 mg litre(-1) of clavulanic acid). From a single
      administration it is proposed that an intramuscular dosage regimen of 105 mg kg(
      1) of the combination (84 mg kg(-1) of amoxicillin and 21 mg kg(-1) of clavulanic
      acid) every 12 hours will achieve minimum concentrations > or =0.5 mg litre(-1)
      (minimum inhibitory concentration of most susceptible pathogens).

PMID- 9769078
TI  - Biochemical analysis of serum and cerebrospinal fluid in clinically normal adult
      camels (Camelus dromedarius).
AB  - The concentrations of total protein, glucose, cholesterol, triglyceride, urea
      nitrogen, creatinine, sodium, potassium, chloride, calcium, inorganic phosphorus,
      copper, magnesium, and iron and the activities of aspartate aminotransferase
      (AST), alanine aminotransferase, (ALT), alkaline phosphatase (ALP), lactate
      dehydrogenase (LD), creatine kinase (CK) and amylase were determined in
      cerebrospinal fluid (CSF) and serum from 21 clinically healthy adult camels. The
      concentrations of sodium, potassium and chloride in CSF were similar to those of
      serum; whereas the values for all other constituents were significantly higher
      (P<0.05) in serum than in CSF.

PMID- 9769079
TI  - Species identification of Streptococcus porcinus by restriction fragment length
      polymorphism analysis of 16S ribosomal DNA.
AB  - Streptococcus porcinus reference strains and routine isolates belonging to
      Lancefield's serogroup E, P, U and V and to various serotypes of serogroup E were
      examined for their 16S ribosomal DNA fingerprint pattern. Oligonucleotide primers
      complementary to 16S rRNA genes were used to amplify gene fragments by polymerase
      chain reaction from genomic DNA. The amplified 1450 bp fragment was subsequently
      digested with the restriction enzyme BpiI resulting in two fragments with a size
      of approximately 1250 bp and 200 bp. All 45 S porcinus investigated in the
      present study could be identified on the basis of this characteristic 16S rDNA
      fingerprint pattern and clearly differentiated from 16 control strains of various
      species and serogroups of genus Streptococcus. The present results demonstrate
      the potential application of 16S rDNA analysis for identification of S porcinus,
      a species which might express various group- and type-specific antigens.

PMID- 9769080
TI  - Neopterin values in selected groups of normal animals.
AB  - To establish baseline information on neopterin concentrations in livestock,
      companion and laboratory animals and identify the factors that may influence
      these concentrations, blood samples were taken from normal dairy cattle, horses,
      llamas, dogs, cats and rats of varying ages and sexes. In addition, neopterin
      concentrations in normal, adult equines were compared with those found in racing
      Thoroughbreds. There were no differences due to sex, sexual maturity, pregnancy,
      castration, or age. For all ages and sexes combined, mean neopterin
      concentrations were significantly lower in llamas (2.27+/-0.33 nmol litre(-1))
      and rats (2.13+/-0.21 nmol litre(-1)) when compared with the other species
      tested. Racing Thoroughbreds demonstrated higher neopterin values than adult
      equines not in training (3.54+/-0.64 vs 3.13+/-1.02 nmol litre(-1)).

PMID- 9769081
TI  - Application of genetic methods to study the relationship between classical swine
      fever outbreaks.
AB  - Eleven viruses isolated between 1993 and 1997 from outbreaks of classical swine
      fever in the neighbouring countries of Slovakia, The Czech Republic and Austria
      were compared after partial sequencing of the NS5B and E2 genes. Viruses
      collected from South-Central and West Slovakia were indistinguishable during a
      period of four years, even when associated with outbreaks of variable severity.
      Outbreaks that occurred in the Czech Republic in 1996 involved two types of
      virus, one of which was related to the Slovakian outbreaks, and the other to
      Austrian outbreaks. The results show that the molecular-genetic approach can
      reveal epizootiological relationships between outbreaks that would not otherwise
      be apparent. Furthermore, the relative genetic stability of the classical swine
      fever virus in the field, means that quite small sequence differences can have
      epizootiological significance.

PMID- 9769083
TI  - Designing for consumers.

PMID- 9769082
TI  - Equine peripheral blood mononuclear cells proliferate in response to tetanus
      toxoid antigen.
AB  - It has been reported that equine peripheral blood mononuclear cells (PBMNs) do
      not proliferate in response to tetanus toxoid (TT) (Frayne and Stokes 1995,
      Research in Veterinary Science 59, 79-81). Here we demonstrate that lymphocyte
      proliferation responses to TT, which are characteristic of a recall antigen, may
      be achieved under certain culture conditions. Given that TT vaccination is
      routinely applied to many horses, TT is a suitable antigen for the investigation
      of cellular immune responses by peripheral blood mononuclear cells in the horse.

PMID- 9769084
TI  - Applying the BeSafe method to product safety evaluation.
AB  - The BeSafe (Behavioural Safety) Method, has been developed by International
      Mining Consultants Ltd for assessing and reducing risk in industrial contexts.
      BeSafe is an ergonomic method of risk analysis and reduction, targeted at
      prevention of accidents due to human errors and violations, and emphasising
      management strategies for action. In a consumer product environment, accidents
      are often due to similar human errors and violations. However, the product usage
      environment tends to be diffuse and variable, and its management difficult. Many
      controlling measures used to prevent accidents in industry do not apply in this
      environment. Using the BeSafe Method, it may be possible to structure safety
      assessments of the use of products and target improvement measures. The authors
      tested the relevant parts of the method on children's play equipment in
      playgrounds, and useful results were obtained. BeSafe could be adapted for other
      consumer products in a similar way.

PMID- 9769085
TI  - Safety pictograms: are they getting the message across?
AB  - This study set out to investigate the role of pictograms in conveying consumer
      safety information. The experimental work was carried out in two parts. The first
      part investigated UK comprehension levels of 13 product related pictograms. A new
      method of judging levels of comprehension of the pictograms was developed. In
      general the pictograms surveyed were found to be poorly understood, particularly
      those which were abstract in nature. The second part of the research investigated
      the effect of different warning styles on noticeability and intended compliance.
      This was tested using the new European Standard pictogram developed to convey the
      small parts warning on toys. The effect on parents' intended purchase decisions
      of different pictograms and or text messages was investigated. Results indicated
      that parents' decisions on toy suitability were influenced by the perceived
      hazardousness of the product rather than warnings, regardless of their design.
      The paper discusses the advantages and limitations of pictograms as a method for
      conveying consumer information and makes recommendations for their effective use.

PMID- 9769086
TI  - Human factors for pleasure in product use.
AB  - Traditionally, human factors have tended to concentrate on making products
      'usable'--focusing on utilitarian, functional product benefits. This paper
      reports an interview-based study looking at the issue of 'pleasure' in product
      use. The study was a 'first pass' at addressing the hedonic and experiential
      benefits and penalties associated with product use, and at identifying the
      properties of a product that influence how pleasurable or displeasurable it is to
      use. Feelings associated with using pleasurable products included security,
      confidence, pride, excitement and satisfaction. Displeasurable products,
      meanwhile, were associated with feelings that included annoyance, anxiety,
      contempt and frustration. The properties of products that were salient in terms
      of influencing the level of pleasure/displeasure with a product included
      features, usability, aesthetics, performance and reliability. Responses to
      questions investigating behavioural correlates to pleasure in product use
      suggested that pleasurable products were used more regularly and that future
      purchase choices would be affected by the level of pleasure in product use. It is
      concluded that the issue of pleasure in product use involves more than usability
      alone. As the user's representative in the product creation process, the human
      factors specialist should consider many other factors in order to ensure that the
      user's experience of product use is maximised.

PMID- 9769087
TI  - Mattress evaluation--assessment of contact pressure, comfort and discomfort.
AB  - The ergonomic evaluation of mattresses is largely ignored in the current
      literature. This is somewhat surprising given their importance and the length of
      time spent using them. This study considers some ergonomic aspects of their
      design, including body contact pressure and subjective ratings of comfort.
      Subjects (12 females) found all of the mattresses tested to be significantly more
      comfortable than an incompressible wooden reference surface. However, no
      significant differences were found between mattress types, which included
      orthopaedic and normal designs. Analysis of body contact pressures (measured at
      the shoulder, elbow, hip, knee and ankle) found few significant differences
      between experimental conditions. It is argued that limitations in the methodology
      may not take account of the change in surface area and anatomical sites of
      contact under different conditions of mattress compressibility. No significant
      associations were found between comfort ratings and peak body contact pressures.
      It seems likely that subjective ratings of mattress comfort are dependent on a
      wider set of factors than contact pressure alone, a finding reported elsewhere in
      studies of seating.

PMID- 9769088
TI  - Is utility in the mind of the beholder? A study of ergonomics methods.
AB  - This paper reviews the use of ergonomics methods in the context of usability of
      consumer products. A review of the literature indicated that there is upward of
      60 methods available to the ergonomist. The results of the survey indicated that
      questionnaires, interviews and observation are the most frequently reported
      methods used. Ease of use of the methods was dependent upon type of method used,
      presence of software support and type of training received. Strong links were
      found between questionnaires and interviews as a combined approach, as well as
      with HTA and observation. However, a questionnaire survey of professional
      ergonomists found that none of the respondents had any documented evidence of the
      reliability and validity of the methods they were using. A study of training
      people to use ergonomics' methods indicated the different requirements of the
      approaches, in terms of training time, application time and subjective
      preferences. An important goal for future research is to establish the
      reliability and validity of ergonomics methods.

PMID- 9769089
TI  - Ergonomics in consumer product evaluation: an evolving process.
AB  - As part of its commitment to empowering people to make informed consumer
      decisions, the Consumers' Association investigates the convenience aspects of a
      vast range of products, from cars to garden spades. Evaluation approaches include
      user trials, convenience checklists and expert appraisals. Our methodology is
      subject to constant review and refinement to ensure the highest levels of
      reliability, validity and auditability. We have a distinctive approach: our tests
      are designed to reflect consumer usage and to provide comparative data which is
      absolutely fair to all products. This paper discusses the evolving nature of that
      methodology within the "lifetime" of a product. Reasons for choosing each method
      are given as practical guidance for those involved in comparative testing.

PMID- 9769090
TI  - Legibility of video-blended TV menus.
AB  - This article describes three experiments relating to the legibility of TV menus.
      Special emphasis is placed on the influence of a relatively new feature in TVs:
      the possibility to blend graphics and video. Three experiments are presented: one
      concentrating on the influences of blending level and video content; one
      concentrating on the influences of content and of colour combinations; and one
      concentrating on the influences of various font characteristics. The results are
      interpreted in terms of guidelines for blended TV menus.

PMID- 9769091
TI  - Testing usability with 3D paper prototypes--Case Halton system.
AB  - In our study, we set out to see how low-fidelity three-dimensional paper
      prototypes could be used to test the usability of two alternative concepts for a
      drink can refund machine. The tests were carried out in the real environment with
      the actual users of the product. The tests took place before any software or
      hardware had been implemented. Using paper prototypes is a quantitative
      evaluation method which is easy to apply and suitable for product development
      processes with a tight schedule. We found the 3DPP modeling and testing method
      turned out to be useful and the results obtained had an influence on the product.

PMID- 9769092
TI  - Usage centred research for everyday product design.
AB  - Prospective users of a new design in the area of everyday products offer
      innumerable opportunities for measurement and observation, in view of both the
      diversity in user populations and the freedom of where and how to use a product.
      In this paper, the relevance of human data is assessed for their impact in
      meeting functional imperatives in a design. On the basis of empirical studies,
      the significance of the observation/registration of user activities, including
      perceptual and cognitive activities, and the use of actions actually carried out
      is demonstrated. For everyday products, these activities are found to be only
      loosely related to human characteristics such as sensory capacities, body
      dimensions and exertable forces. Such characteristics seem to combine a limited
      relevance for usage centred design with relatively easy measurability. In
      contrast, observation of user activities may be evasive and is often laborious.
      User trialling is seen as an obvious way to enable designers to accommodate
      prospective user activities in everyday product design.

PMID- 9769093
TI  - A quantitative study of the flexibility contributed to RNA structures by nicks
      and single-stranded gaps.
AB  - Disulfide crosslinking via thiol-disulfide interchange was applied to quantitate
      the relative flexibility contributed by nicks and single-stranded gaps in an RNA
      structure. An RNA duplex comprised of three strands was constructed containing
      the disulfide crosslink precursors 1 and 2 at opposite ends of the duplex on
      opposite strands. The third strand was of varying length to yield a nick or
      single-stranded gaps of 1, 2, or 3 nt. Crosslinking rates Indicated relative
      flexibilities of the resulting two-helix junctions. Crosslinking in the nicked
      duplex occurred two orders of magnitude slower than in a duplex containing a 3-nt
      gap. Rates of crosslinking in duplexes with 3-and 2-nt gaps showed only modest
      dependence on the gap sequence. Many natural RNAs, including ribozymes, contain
      two-helix junctions related to the model system described here. The data suggest
      that two-helix junctions containing a nick in one strand will retain substantial
      rigidity, whereas one or more single-stranded nucleotides at a two-helix junction
      allow significant flexibility.

PMID- 9769094
TI  - More than one way to splice an RNA: branching without a bulge and splicing
      without branching in group II introns.
AB  - Domain 6 (D6) of group II introns contains a bulged adenosine that serves as the
      branch-site during self-splicing. In addition to this adenosine, other structural
      features in D6 are likely to contribute to the efficiency of branching. To
      understand their role in promoting self-splicing, the branch-site and surrounding
      nucleotides were mutagenized. Detailed kinetic analysis on the self-splicing
      efficiency of the mutants revealed several interesting features. First,
      elimination of the branch-site does not preclude efficient splicing, which takes
      place instead through a hydrolytic first step. Second, pairing of the branch-site
      does not eliminate branching, particularly if the adenosine is involved in a
      mispair. Third, the G-U pairs that often surround group II intron branch-points
      contribute to the efficiency of branching. These results suggest that there is a
      strong driving force for promoting self-splicing by group II introns, which
      employ a versatile set of different mechanisms for ensuring that splicing is
      successful. In addition, the behavior of these mutants indicates that a bulged
      adenosine per se is not the important determinant for branch-site recognition in
      group II introns. Rather, the data suggest that the branch-site adenosine is
      recognized as a flipped base, a conformation that can be promoted by a variety of
      different substructures in RNA and DNA.

PMID- 9769095
TI  - Structure and stability of variants of the sarcin-ricin loop of 28S rRNA: NMR
      studies of the prokaryotic SRL and a functional mutant.
AB  - NMR has been used to examine the conformational properties of two variants of the
      sarcin-ricin loop (SRL) from eukaryotic 28S rRNA, which is essential for
      elongation factor interactions with the ribosome: (1) its bacterial homologue,
      which lacks two of the bases that flank the conserved 12-nt sequence in the
      middle of the SRL, but which is functionally equivalent, and (2) a functionally
      active variant of the eukaryotic SRL in which the bulged G within the conserved
      sequence is replaced by an A. The data indicate that, although the bacterial SRL
      is less stable than the eukaryotic SRL, its conformation is closely similar.
      Furthermore, even though replacement of the bulged G in the SRL with an A
      seriously destabilizes the center of the loop, its effect on the overall
      conformation of the SRL appears to be modest. In the course of this work, it was
      serendipitously discovered that at neutral pH, the C8 proton of the bulged G, in
      both PRO-SRL and E73, exchanges about 10 times faster than it does in GMP.

PMID- 9769096
TI  - PRP16, a DEAH-box RNA helicase, is recruited to the spliceosome primarily via its
      nonconserved N-terminal domain.
AB  - Dynamic rearrangement of RNA structure is crucial for intron recognition and
      formation of the catalytic core during pre-mRNA splicing. Three of the splicing
      factors that contain sequence motifs characteristic of the DExD/DExH-box family
      of RNA-dependent ATPases (Prp16, Prp22, and the human homologue of Brr2) recently
      have been shown to unwind RNA duplexes in vitro, providing biochemical evidence
      that they may direct structural rearrangements on the spliceosome. Notably,
      however, the unwinding activity of these proteins is sequence nonspecific,
      raising the question of how their functional specificity is determined. Because
      the highly conserved DExD/DExH-box domain in these proteins is typically flanked
      by one or more nonconserved domains, we have tested the hypothesis that the
      nonconserved regions of Prp16 determine the functional specificity of the
      protein. We found that the nonconserved N-terminal domain of Prp16 is (1)
      essential for viability, (2) required for the nuclear localization of Prp16, and
      (3) capable of binding to the spliceosome specifically at the step of Prp16
      function. Moreover, this domain can interact with the rest of the protein to
      allow trans-complementation. Based on these results, we propose that the
      spliceosomal target of the unwinding activity of Prp16, and possibly other
      DExD/DExH-box splicing factors as well, is defined by factors that specifically
      interact with the nonconserved domains of the protein.

PMID- 9769097
TI  - Programmed frameshifting in the synthesis of mammalian antizyme is +1 in mammals,
      predominantly +1 in fission yeast, but -2 in budding yeast.
AB  - The coding sequence for mammalian ornithine decarboxylase antizyme is in two
      different partially overlapping reading frames with no independent ribosome entry
      to the second ORF. Immediately before the stop codon of the first ORF, a
      proportion of ribosomes undergo a quadruplet translocation event to shift to the
      +1 reading frame of the second and main ORF. The proportion that frameshifts is
      dependent on the polyamine level and, because the product antizyme is a negative
      regulator of intracellular polyamine levels, the frameshifting acts to complete
      an autoregulatory circuit by sensing polyamine levels. An mRNA element just 5' of
      the shift site and a 3' pseudoknot are important for efficient frameshifting.
      Previous work has shown that a cassette with the mammalian shift site and
      associated signals directs efficient shifting in the budding yeast Saccharomyces
      cerevisiae at the same codon to the correct frame, but that the shift is -2
      instead of +1. The product contains an extra amino acid corresponding to the
      shift site. The present work shows efficient frameshifting also occurs in the
      fission yeast, Schizosaccharomyces pombe. This frameshifting is 80% +1 and 20% 
      2. The response of S. pombe translation apparatus to the mammalian antizyme
      recoding signals is more similar to that of the mammalian system than to that of
      S. cerevisiae. S. pombe provides a good model system for genetic studies on the
      mechanism of at least this type of programmed mammalian frameshifting.

PMID- 9769098
TI  - Protein-RNA interactions in the U5 snRNP of Saccharomyces cerevisiae.
AB  - We present here the first insights into the organization of proteins on the RNA
      in the U5 snRNP of Saccharomyces cerevisiae. Photo-crosslinking with uniformly
      labeled U5 RNA in snRNPs reconstituted in vitro revealed five contacting
      proteins, Prp8p, Snu114p, p30, p16, and p10, contact by the three smaller
      proteins requiring an intact Sm site. Site-specific crosslinking showed that
      Snu114p contacts the 5' side of internal loop 1, whereas Prp8p interacts with
      five different regions of the 5' stem-loop, but not with the Sm site or 3' stem
      loop. Both internal loops in the 5' domain are essential for Prp8p to associate
      with the snRNP, but the conserved loop 1 is not, although this is the region to
      which Prp8p crosslinks most strongly. The extensive contacts between Prp8p and
      the 5' stem-loop of U5 RNA support the hypothesis that, in spliceosomes, Prp8p
      stabilizes loop 1-exon interactions. Moreover, data showing that Prp8p contacts
      the exons even in the absence of loop 1 indicate that Prp8p may be the principal
      anchoring factor for exons in the spliceosome. This and the close proximity of
      the spliceosomal translocase, Snu114p, to U5 loop 1 and Prp8p support and extend
      the proposal that Snu114p mimics U5 loop 1 during a translocation event in the
      spliceosome.

PMID- 9769099
TI  - Cryoenzymology of the hammerhead ribozyme.
AB  - The technique of cryoenzymology has been applied to the hammerhead ribozyme in an
      attempt to uncover a structural rearrangement step prior to cleavage. Several
      cryosolvents were tested and 40% (v/v) methanol in water was found to perturb the
      system only minimally. This solvent allowed the measurement of ribozyme activity
      between 30 and -33 degrees C. Eyring plots are linear down to -27 degrees C, but
      a drastic reduction in activity occurs below this temperature. However, even at
      extremely low temperatures, the rate is still quite pH dependent, suggesting that
      the chemical step rather than a structural rearrangement is still rate-limiting.
      The nonlinearity of the Eyring plot may be the result of a transition to a cold
      denatured state or a glassed state.

PMID- 9769100
TI  - The RNA recognition motif of yeast translation initiation factor Tif3/eIF4B is
      required but not sufficient for RNA strand-exchange and translational activity.
AB  - The Saccharomyces cerevisiae TIF3 gene encodes a 436-amino acid (aa) protein that
      is the yeast homologue of mammalian translation Initiation factor eIF4B. Tif3p
      can be divided into three parts, the N-terminal region with an RNA recognition
      motif (RRM) (aa 1-182), followed in the middle part by a sevenfold repeat of 26
      amino acids rich in basic and acidic residues (as 183-350), and a C-terminal
      region without homology to any known sequence (aa 351-436). We have analyzed
      several Tif3 proteins with deletions at their N and C termini for their ability
      (1) to complement a tif3delta strain in vivo, (2) to stimulate Tif3-dependent
      translation extracts, (3) to bind to single-stranded RNA, and (4) to catalyze RNA
      strand-exchange in vitro. Here we report that yeast Tif3/eIF4B contains at least
      two RNA binding domains able to bind to single-stranded RNA. One is located in
      the N-terminal region of the protein carrying the RRM, the other in the C
      terminal two-thirds region of Tif3p. The RRM-containing domain and three of the
      seven repeat motifs are essential for RNA strand-exchange activity of Tif3p and
      translation in vitro and for complementation of a tif3delta strain, suggesting an
      important role for RNA strand-exchange activity in translation.

PMID- 9769101
TI  - Spb4p, an essential putative RNA helicase, is required for a late step in the
      assembly of 60S ribosomal subunits in Saccharomyces cerevisiae.
AB  - Spb4p is a putative ATP-dependent RNA helicase that is required for synthesis of
      60S ribosomal subunits. Polysome analyses of strains genetically depleted of
      Spb4p or carrying the cold-sensitive spb4-1 mutation revealed an
      underaccumulation of 60S ribosomal subunits. Analysis of pre-rRNA processing by
      pulse-chase labeling, northern hybridization, and primer extension indicated that
      these strains exhibited a reduced synthesis of the 25S/5.8S rRNAs, due to
      inhibition of processing of the 27SB pre-rRNAs. At later times of depletion of
      Spb4p or following transfer of the spb4-1 strain to more restrictive
      temperatures, the early pre-rRNA processing steps at sites A0, Al, and A2 were
      also inhibited. Sucrose gradient fractionation showed that the accumulated 27SB
      pre-rRNAs are associated with a high-molecular-weight complex, most likely the
      66S pre-ribosomal particle. An HA epitope-tagged Spb4p is localized to the
      nucleolus and the adjacent nucleoplasmic area. On sucrose gradients, HA-Spb4p was
      found almost exclusively in rapidly sedimenting complexes and showed a peak in
      the fractions containing the 66S pre-ribosomes. We propose that Spb4p is involved
      directly in a late and essential step during assembly of 60S ribosomal subunits,
      presumably by acting as an rRNA helicase.

PMID- 9769102
TI  - Metal ion probing of rRNAs: evidence for evolutionarily conserved divalent cation
      binding pockets.
AB  - Ribosomes are multifunctional RNP complexes whose catalytic activities absolutely
      depend on divalent metal ions. It is assumed that structurally and functionally
      important metal ions are coordinated to highly ordered RNA structures that form
      metal ion binding pockets. One potent tool to identify the structural
      surroundings of high-affinity metal ion binding pockets is metal ion-induced
      cleavage of RNA. Exposure of ribosomes to divalent metal ions, such as Pb2+,
      Mg2+, Mn2+, and Ca2+, resulted in site-specific cleavage of rRNAs. Sites of
      strand scission catalyzed by different cations accumulate at distinct positions,
      indicating the existence of general metal ion binding centers in the highly
      folded rRNAs in close proximity to the cleavage sites. Two of the most efficient
      cleavage sites are located in the 5' domain of both 23S and 16S rRNA, regions
      that are known to self-fold even in the absence of ribosomal proteins. Some of
      the efficient cleavage sites were mapped to the peptidyl transferase center
      located in the large ribosomal subunit. Furthermore, one of these cleavages was
      clearly diminished upon AcPhe-tRNA binding to the P site, but was not affected by
      uncharged tRNA. This provides evidence for a close physical proximity of a metal
      ion to the amino acid moiety of charged tRNAs. Interestingly, comparison of the
      metal ion cleavage pattern of eubacterial 70S with that of human 80S ribosomes
      showed that certain cleavage sites are evolutionarily highly conserved, thus
      demonstrating an identical location of a nearby metal ion. This suggests that
      cations, bound to evolutionarily constrained binding sites, are reasonable
      candidates for being of structural or functional importance.

PMID- 9769103
TI  - Correlation between bending of the VM region and pathogenicity of different
      Potato Spindle Tuber Viroid strains.
AB  - Only 40 of the 359 nucleotides of Potato Spindle Tuber Viroid (PSTVd) represent
      the virulence-modulating (VM) region. Minor sequence variations in this domain
      distinguish mild from severe and even necrotic strains. Our recent hypothesis
      (Owens RA et al., 1996, Virology 222:144-158) that these differences result in
      varying degrees of bending of this part of the molecule could be tested
      experimentally. By in vitro transcription and partial double-strand formation,
      three types of model RNAs were prepared and subjected to electrophoresis in
      polyacrylamide gels: (1) Fragments representing the VM regions of six different
      PSTVd strains; (2) control fragments containing a bulge-loop as a rigid bend or
      an internal loop as a point of increased flexibility; and (3) dsRNAs of 36, 39,
      and 43 bp as length standards. Migration anomalies in gels of increasing
      percentage were evaluated and resulted in the following conclusions. In the
      absence of Mg2+, the VM regions differ only in terms of flexibility. Addition of
      Mg2+ induces conformational changes in these RNAs. All strains but Mild exhibit a
      rigid bend, and the angle of bending increases monotonically with the
      pathogenicity of the strain. The data are discussed in terms of a mechanism of
      pathogenicity, that protein-binding to the VM region is the primary pathogenic
      event.

PMID- 9769104
TI  - Identification and functional analysis of hPRP17, the human homologue of the
      PRP17/CDC40 yeast gene involved in splicing and cell cycle control.
AB  - The PRP17 gene of the yeast Saccharomyces cerevisiae encodes a protein that
      participates in the second step of the splicing reaction. It was found recently
      that the yeast PRP17 gene is identical to the cell division cycle CDC40 gene. The
      PRP17/CDC40 gene codes for a protein with several copies of the WD repeat, a
      motif found in a large family of proteins that play important roles in signal
      transduction, cell cycle progression, splicing, transcription, and development.
      In this report, we describe the identification of human, nematode, and fission
      yeast homologues of the PRP17/CDC40 gene of S. cerevisiae. The newly identified
      proteins share homology with the budding yeast protein throughout their entire
      sequence, with the similarity being greatest in the C-terminal two thirds that
      includes the conserved WD repeats. We show that a yeast-human chimera, carrying
      the C-terminal two thirds of the hPRP17 protein, is able to complement the cell
      cycle and splicing defects of a yeast prp17 mutant. Moreover, the yeast and yeast
      human chimeric proteins co-precipitate the intron-exon 2 lariat intermediate and
      the intron lariat product, providing evidence that these proteins are spliceosome
      associated. These results show the functional conservation of the Prp17 proteins
      in evolution and suggest that the second step of splicing takes place by a
      similar mechanism throughout eukaryotes.

PMID- 9769105
TI  - T7 RNA polymerase produces 5' end heterogeneity during in vitro transcription
      from certain templates.
AB  - The use of T7 RNA polymerase to prepare large quantities of RNA of a particular
      sequence has greatly facilitated the study of both the structure and function of
      RNA. Generally, it has been believed that the products of this technique are
      highly homogeneous in sequence, with only a few noted exceptions. We have
      carefully examined the transcriptional products of several tRNAs that vary in
      their 5' end sequence and found that, for those molecules that begin with
      multiple, consecutive guanosines, the transcriptional products are far from
      homogenous. Although a template beginning with GCG showed no detectable 5' end
      heterogeneity, two tRNA templates designed to have either four or five
      consecutive guanosines at their 5' ends had more than 30% of their total
      transcriptional products extended by at least one untemplated nucleotide at their
      5' end. By simply reducing the number of consecutive guanosines, the
      heterogeneity was reduced significantly. The presence of this 5' end
      heterogeneity in combination with the 3' end heterogeneity common to T7
      transcriptions results in a mixture of RNA molecules even after rigorous size
      purification.

PMID- 9769106
TI  - Biomarkers in toxicology.
AB  - The use of biomarkers in toxicology is becoming increasingly important. This
      article briefly reviews some of the aspects in an attempt to give an overall view
      of the field. Some of the new developments, particularly in relation to
      biomarkers of exposure and response, are mentioned. Specific DNA and protein
      adducts can now be used as biomarkers of the effective exposure so incorporating
      variations in environmental levels and individual disposition. Analysis of
      urinary metabolite profiles by NMR can highlight novel markers and allow
      recognition of patterns of metabolite changes as biomarkers of a toxic response.
      Novel urinary markers for liver and testicular dysfunction are discussed.
      Finally, the acetylator phenotype as a biomarker of susceptibility is described.

PMID- 9769107
TI  - Experimental studies on immunosuppression: how do they predict for man?
AB  - The ultimate goal of any animal model in immunotoxicity testing is that it be a
      sensitive predictor of xenobiotic-induced immune dysfunction in humans. Such
      models should be capable of identifying the target(s) within the immune system
      affected by the xenobiotic. In particular the tier testing models have been
      successfully used to identify and characterize a variety of different
      immunotoxicants in animals as it pertains to immunosuppression and reduced
      resistance to infectious diseases. These tier models in mice and rats have been
      validated in interlaboratory studies. Although these protocols were designed for
      studies of rats and mice, some have been applied successfully for studying
      immunotoxicity in other animal species, including non-human primates. A great
      amount of data has been generated by the application of these models, which
      demonstrate that xenobiotics alter the immune system of animals. In man, the
      database on chemical-induced immunosuppression is limited, as the use of markers
      of immunotoxicity has received little attention in clinical and epidemiological
      studies. Such studies have not been performed frequently, and their
      interpretation often does not permit unequivocal conclusions to be drawn, due for
      instance to the presence of confounding factors and the uncontrolled nature of
      exposure. Also, testing possibilities in humans are limited and immune function
      changes by chemical exposure are often subtle. In humans, a number of agents have
      been shown to have immunosuppressive properties (including PCBs, PCDDs, PCDFs,
      oxidant gases, and ultraviolet radiation), but the strongest evidence stems from
      the clinical use of immunosuppressant drugs in transplant patients. These human
      data do in general terms confirm the data gained with experimental animals.
      Immunotoxicity assessment in rodents therefore adequately forms the basis for
      human risk assessment. Knowledge on the predictability of these animal models and
      immune assays can be further improved by comparison of the human and animal data
      obtained in the development of drugs.

PMID- 9769108
TI  - Value of animal models for predicting hypersensitivity reactions to medicinal
      products.
AB  - Although hypersensitivity reactions induced by medicinal products and chemicals
      are relatively common, few predictive models are available. A major difficulty is
      our currently limited understanding of the mechanisms involved, and efforts
      should be paid to better defining drug immunogenicity, hapten formation and
      immune effector mechanisms. A second difficulty is the multiplicity of clinical
      manifestations presumably due to varying mechanisms. Available models can only
      predict a few of these reactions. Anaphylaxis models in guinea-pigs can be only
      used for the safety assessment of macromolecules which are neither humanized or
      of human origin, whereas guinea-pig or mouse models can detect the majority of
      human contact sensitizers. In addition to the extensive validation of existing
      models, promising avenues of research are expected to be found in the use of
      novel animal models, particularly those using genetically modified animals, such
      as transgenic and knock-out mice.

PMID- 9769109
TI  - Epidemiology studies in immunotoxicity evaluations.
AB  - Studies in humans designed to detect immunomodulation from exposure to
      xenobiotics present challenging problems to epidemiologists and
      immunotoxicologists. Exposed and control groups must be carefully selected,
      exposure to the xenobiotic must be sufficiently high and well-documented, and the
      referent group should be as similar as possible to the exposed. Immune
      markers/functional tests in an individual may be influenced by sunlight exposure,
      medication, illness and use of recreational drugs; all of these potential
      confounding factors must be addressed. Sample acquisition is usually performed at
      sites geographically distant from the controlled environment of an investigator's
      laboratory, yielding an assortment of new problems that would not occur in
      clinical or hospital situations. Regulations and guidelines concerning the
      transport of biological samples and potential hazards of HIV and HBV exposures to
      personnel must be adapted to field conditions. Since the application of
      immunotoxicological techniques to populations exposed to xenobiotics is
      relatively new, and the ability to measure an increasing number of immune
      biomarkers of activation, suppression, autoimmunity or hypersensitivity is
      rapidly expanding, there are difficulties in the interpretation of statistically
      positive results (sometimes within the normal range) and their potential health
      significance. Finally, both biological and methodological factors complicate the
      assessment of dose-response/concentration effect relationships in human
      immunotoxicity studies, and traditional dose-response relationships may not
      always be present.

PMID- 9769110
TI  - Cytokine assays in human sera and tissues.
AB  - The use of accurate and sensitive methods for the measurement of cytokines in
      body fluids is an absolute prerequisite for the proper use of these mediators in
      clinical practice. Many factors contribute to the complexity of cytokines
      quantitation: these molecules circulate at very low levels (e.g. pg/ml) under
      various molecular forms, the existence of circadian rhythms has been described,
      and the presence of inhibitors (binding proteins, soluble receptors,
      autoantibodies) can potentially interfere in the assays. Blood collection for
      cytokines needs particular attention to prevent possible contamination by
      endotoxins, which can trigger cytokines cellular production after sampling.
      Bioassays historically preceded immunoassays; the latter techniques are now very
      popular, but there is an urgent need for standardisation between the different
      kits commercially available. Nevertheless, due to the essentially local effects
      of cytokines, the study of their circulating levels only represents the 'tip of
      the iceberg' and is of limited value for a global understanding of the
      pathophysiology of these mediators. This explains the development of other
      approaches to assess the ability of cells to produce cytokines. These include the
      ELISPOT assay, the measurement of cell-associated cytokines by flow cytometry,
      and the study of cytokine secretion by isolated peripheral blood mononuclear
      cells or by whole blood test. All these techniques, associated with a local
      detection of cytokines by immunohistochemistry or in situ hybridization and
      reverse transcriptase polymerase chain reaction (RT-PCR), appear to be
      complementary tools for a better understanding of the multiple aspects of the
      biology of cytokines.

PMID- 9769111
TI  - Biomarkers of immunotoxicity in fish and other non-mammalian sentinel species:
      predictive value for mammals?
AB  - Through the efforts of different laboratories, a battery of immunological assays
      is available to predict the immunotoxicity of xenobiotics. These assays,
      originally developed in rodents, have been adapted for use in a variety of animal
      species and are now used routinely in these models to assess the immunotoxicity
      of different chemical classes. For example, our laboratory has employed assays
      that measure antibody-forming cell response to T-dependent antigens, T- and B
      cell lymphoproliferation, macrophage function, and host resistance against
      infectious bacteria to assess metal-induced immunotoxicity in laboratory-reared
      Japanese medaka (Oryzias latipes); immunologically-related assays measuring
      antioxidant activity have also been used in this capacity. Results of the
      aforementioned investigations have shown the usefulness of these endpoints to
      reliably demonstrate chemical-mediated immunotoxicity in teleost systems. Many of
      these same endpoints have also proved successful for predicting the immunotoxic
      effects of contaminated aquatic environments in feral fish populations. For
      example, smallmouth bass collected from a chlorinated hydrocarbon-contaminated
      site demonstrated significant changes in blood cell profiles and kidney phagocyte
      function compared to fish collected from a 'clean water' reference site. Some of
      these same immune parameters have also been used successfully to predict the
      immunotoxicity of polluted aquatic environments in feral populations of fish
      eating birds and harbor seals. While interspecies extrapolation is difficult and
      should be approached with caution due to variables such as metabolism and
      pharmacokinetics, results from these studies demonstrate the usefulness of these
      immune assays to predict the immunomodulating effects of xenobiotics in fish and
      other wildlife species, as well as the applicability of fish to serve as
      additional/alternate animal models for mammalian species in immunotoxicological
      studies.

PMID- 9769112
TI  - Application of immunologic methods in clinical trials.
AB  - Immunologic effects of a new pharmaceutical molecule are often studied by in
      vitro immune assays and in laboratory animal models. However, immunologic
      activity can also be evaluated in man during the early clinical stage of drug
      development. Measures of immunologic response have recently served as surrogate
      clinical endpoints for drug approval. A variety of non-invasive measures can
      determine if a test molecule enhances or suppresses immunity. Both antibody and
      cellular immune responses to a new molecule itself can be detected and quantified
      in man. Assuring the successful outcome of a clinical trial incorporating
      immunologic parameters however, requires a realistic approach to protocol
      development, care in site selection, and a critical evaluation of participating
      laboratories.

PMID- 9769113
TI  - Results of a cyclosporin A ringstudy.
AB  - The aim of the study was to find out whether an extended subacute toxicity study
      (additional organ weights, histopathology and immune functional tests), routinely
      employed in testing of chemicals, would shown indications of (adverse) effects on
      the immune system below general toxicity. Therefore, a five laboratory ring study
      on the basis of an oral 28-day repeated dose study in rats (OECD guideline 407)
      was carried out with 1, 5 and 25 mg/kg of cyclosporin A (CsA) per day by gavage.
      Besides some toxic effects such as reduced body weight gain and increased kidney
      calcification in the high-dose group, the results of the additional pathologic
      examinations revealed that CsA caused a pattern of specific morphological
      alterations of the lymphoid tissues in mid- and high-dose groups. Selected immune
      parameters such as immunoglobulin determination, plaque-forming assay, flow
      cytometry, activation status of macrophages and natural killer cells (NK), and
      proliferative response of spleenocytes and cells from mesenteric lymph nodes
      (concanvalin A (ConA) and pokeweed mitogen (PWM) stimulation) were also
      investigated. Some results compared to the controls revealed alterations down to
      the low-dose group. The extended methodology consistently indicated the potential
      detection of effects on the immune system below general systemic toxicity. The
      study will be continued by investigating a second compound with primarily
      immunostimulating effects. Results from those studies should further contribute
      to the current discussion of up-dating of repeated dose toxicity guidelines with
      respect to immunotoxicity.

PMID- 9769114
TI  - T cell-tumor cell: a fatal interaction?
AB  - Fas (Apo-1/CD95) is a cell-surface protein that is responsible for initiating a
      cascade of proteases (caspases) culminating in apoptotic cell death in a variety
      of cell types. The function of the Fas/FasL system in the dampening of immune
      responses to infectious agents through the autocrine deletion of activated T
      cells has been well documented. More recently, it has been proposed that tumor
      cells express FasL, presumably to avoid immune detection. In this review, we
      focus on the role of the interaction of Fas and FasL in the modulation of
      antitumor responses. We critically examine the evidence that FasL is expressed by
      tumor cells and explore alternative explanations for the observed phenomena in
      vitro and in vivo. By reviewing data that we have generated in our laboratory as
      well as reports from the literature, we will argue that the Fas/FasL system is a
      generalized mechanism used in an autocrine fashion to regulate cell survival and
      expansion in response to environmental and cellular cues. We propose that FasL
      expression by tumor cells, when present, is indicative of a perturbed balance in
      the control of proliferation while "immune privilege" is established by "suicide"
      of activated antitumor T cells, a form of activation-induced cell death.

PMID- 9769115
TI  - Irradiated tumor cells adenovirally engineered to secrete granulocyte/macrophage
      colony-stimulating factor establish antitumor immunity and eliminate pre-existing
      tumors in syngeneic mice.
AB  - The specific aim of this study was to examine the prophylactic as well as the
      therapeutic efficacies of irradiated mouse CT26 colon cancer cells, infected with
      recombinant adenoviruses harboring cDNAs specific for granulocyte macrophage
      colony-stimulating factor (GM-CSF), interferon (IFN-gamma) and monocyte
      chemotactic protein1 (MCP-1). Results showed that tumor cells secrete the
      respective cytokines for several days after infection and subsequent irradiation.
      Vaccination with irradiated GM-CSF-secreting CT26 cells protected 90% of
      syngeneic mice challenged with live parental cells. On the other hand,
      vaccination with irradiated IFNgamma or MCP-1-secreting CT26 cells totally failed
      to protect mice from tumor development after challenge with parental cells. None
      of the tumor-free mice initially vaccinated with irradiated GM-CSF-producing CT26
      cells developed tumor upon repeated challenge with parental cells during the
      entire observation period. The establishment of specific and long-lasting
      antitumor immunity following vaccination with GM-CSF-producing tumor cells
      requires the simultaneous presence of GM-CSF and tumor antigen at the vaccine
      site. Depletion of CD8+ cells, but not CD4+ cells, blocked the vaccine efficacy
      of GM-CSF-producing tumor cells. Subcutaneous injection of irradiated GM-CSF
      producing CT26 cells also effectively prevented the growth of a small load of
      parental tumor that was implanted 3 days earlier or the development of metastatic
      foci in the lung from intravenously injected parental cells either 7 days before
      or 3 days after vaccination. Our data thus show that, in these experimental tumor
      models, subcutaneous injection of irradiated tumor cells adenovirally, transduced
      with the GM-CSF gene leads not only to prevention of growth of subsequently
      implanted tumor but also to elimination of pre-existing and metastatic tumors.

PMID- 9769116
TI  - In vitro propagated dendritic cells from patients with human-papilloma virus
      associated preneoplastic lesions of the uterine cervix: use of Flt3 ligand.
AB  - Dendritic cells (DC) are the most efficient antigen presenting cells. The
      clinical use of DC as vectors for antitumor and anti-infectious disease
      immunotherapy has been limited by their low level and accessibility in normal
      tissue. Substantial numbers of DC can be generated from peripheral blood cultured
      in the presence of interleukin-4 (IL-4) and granulocyte/macrophage-colony
      stimulating factor (GM-CSF). We showed in this study that substantial numbers of
      DC can be obtained from the peripheral blood of patients with (pre)neoplastic
      lesions of the uterine cervix. The procedure required relatively small blood
      samples (10 ml) and the presence of 100 U/ml IL-4 and 800 U/ml GM-CSF in the
      culture medium. There was no significant difference in the morphology, yield,
      phenotype and function of generated DC between patients with cervical
      (pre)neoplastic lesions and healthy individuals. When the hematopoietic factor
      Flt3 ligand (Flt3L, 40 ng;ml) was added, there was an average increase in the DC
      population of 26% compared to cultures with GM-CSF and IL-4 alone. Approximately
      1.2 x 10(6) cells with the characteristics of dendritic cells could be obtained
      when Flt3L was included in the medium. The addition of Flt3L did not modify the
      phenotypic profile of DC (HLA-DR+, CD1a+, CD4+, CD54+, CD80+, CD86+. CD40+, CD3-
      and CD14-). In addition, Flt3L generated functional DC capable of stimulating the
      proliferation of alloreactive T cells. These results suggest that Flt3L, in
      association with GM-CSF and IL-4, provides an advantageous tool for the large
      scale generation of DC and that an immunotherapy based on the use of DC generated
      in vitro is possible in patients with (pre)neoplastic lesions of the uterine
      cervix.

PMID- 9769117
TI  - In vitro induction of HLA-A2402-restricted and carcinoembryonic-antigen-specific
      cytotoxic T lymphocytes on fixed autologous peripheral blood cells.
AB  - HLA-A2402-restricted and carcinoembryonic-antigen(CEA)-specific cytotoxic T
      lymphocytes (CTL) were induced by culturing human peripheral blood mononuclear
      cells (PBMC) on formalin-fixed autologous adhesive PBMC that had been loaded with
      CEA-bound latex beads. The CTL killed the CEA-producing HLA-type matched cancer
      cells, but not the non-producers of CEA, at an effector/target ratio of 10 within
      24 h. On the basis of available HLA-A24-binding peptides, we have also attempted
      to identify the epitope peptide recognized by the CTL. The peptide CEA652(9),
      TYACFVSNL, stimulated the CTL most strongly when pulsed on HLA-A2402-expressing
      target cells. The other nine peptides so far tested were also active, but less
      efficient in their effect on CTL. The CTL failed to kill target cells pulsed with
      the HLA-A2-binding CEA peptide, CAP-1. The CTL were also generated on the fixed
      adherent cells previously pulsed with the peptide CEA652(9). Cytotoxic activity
      of the CTL was inhibited by monoclonal antibodies against CD3, CD8, and MHC class
      I molecules. These results suggest that human autologous CTL will be inducible on
      the autologous fixed PBMC without use of the cultured target cancer cells if
      tumor antigenic protein is available.

PMID- 9769118
TI  - Interleukin-15 effectively potentiates the in vitro tumor-specific activity and
      proliferation of peripheral blood gammadeltaT cells isolated from glioblastoma
      patients.
AB  - GammadeltaT cells play a regulatory role in both primary and metastatic tumor
      growth in humans. The mechanisms responsible for the activation and proliferation
      of circulating gammadeltaT cells should be fully understood prior to their
      adoptive transfer to cancer patients. We have examined in vitro functional
      effects of interleukin-15 (IL-15) on highly purified gammadeltaT cells isolated
      from glioblastoma patients. GammadeltaT cells constitutively express the
      heterotrimeric IL-2 receptor (IL-2R) alpha betagamma, but the levels of IL-2Rbeta
      or gamma expression were not increased by incubation with saturating amounts of
      IL-15. IL-15 was shown to induce a maximal gammadeltaT cell proliferation,
      although at much higher concentrations (at least 2000 U/ml) than IL-2 (100 U/ml).
      Submaximal concentrations of IL-15 plus low concentrations of IL-2 produced an
      additive proliferative response. In contrast to the IL-2-induced response, this
      activity was completely or partially abrogated by anti-IL-2Rbeta, or anti-IL
      2Rgamma antibodies, but not by anti-IL-2R alpha antibodies. Incubation of
      gammadeltaT cells in the presence of IL-15 resulted not only in the appearance of
      NK and LAK activity, but also in specific autologous tumor cell killing activity,
      an additive effect being seen with IL-15 and IL-2. This IL-15-induced tumor
      specific activity could be significantly blocked by anti-IL-2Rgamma and anti-IL
      2R-beta mAb, but not by anti-IL-2R alpha mAb. Thus, in contrast to IL-2, IL-15
      activates tumor-specific gammadeltaT cells through the components of IL-2Rbeta
      and IL-2Rgamma, but not IL-2R alpha. These enhanced in vitro tumor-specific and
      proliferative responses of gammadeltaT cells seen with IL-15 suggest a rational
      adjuvant imunotherapeutic use of gammadeltaT cells in cancer patients.

PMID- 9769119
TI  - CD40-ligation-mediated protection from apoptosis of a Fas-sensitive Hodgkin's
      disease-derived cell line.
AB  - Modulation of Fas expression and function by CD40 ligation was investigated in
      the Fas-sensitive human Hodgkin's disease cell line HDLM2. The recombinant human
      trimeric soluble CD40L (sCD40L) protected this cell line from apoptosis induced
      by an agonistic Fas antibody at all concentrations tested. sCD40L also protected
      HDLM2 when added up to 2 h after Fas ligation. Apoptosis induced by a cell
      permeable synthetic ceramide could not be prevented by sCD40L. Thus, CD40
      ligation is likely to intervene in the early phases of the Fas signal
      transduction pathway. When CD40 ligation preceded Fas ligation, it rendered the
      cells refractory to Fas-induced apoptosis. sCD40L-mediated protection could not
      be attributed to reduction in surface Fas expression, increase in Bcl-2 levels or
      to increase in the levels of soluble Fas isoforms.

PMID- 9769120
TI  - Unresponsiveness to interferon associated with STAT1 protein deficiency in a
      gastric adenocarcinoma cell line.
AB  - HC class I expression can be up-regulated by interferons (IFN) and other
      cytokines. Both IFNalpha and IFNgamma have been shown to exert their effects via
      a recently discovered signalling pathway by inducing tyrosine phosphorylation of
      their receptors. Receptors for interferons and other cytokines signal through the
      action of associated protein tyrosine kinases of the JAK family (Janus kinase)
      and latent cytoplasmic transcriptional activators from the STAT family (signal
      transducers and activators of transcription). Here we report a gastric
      adenocarcinoma cell line, AGS, that is defective in its response to either
      IFNalpha or IFNgamma. AGS cells display selective alterations only in MHC class I
      inducibility and not in constitutive MHC class I expression. In nuclear extracts
      of AGS cells, no binding activity to interferon-responsive elements (GAS/ISRE)
      was observed. We found that AGS cells showed an extremely low level of STAT1
      expression, which may be responsible for the absence of biological response to
      IFN. Because STAT1-deficient cells are highly sensitive to infection by virus,
      the absence of these proteins may also contribute to the tumor phenotype, giving
      the tumor a selective advantage, by inhibiting cell growth suppression mediated
      by IFN and abetting escape from the T cell antitumor response.

PMID- 9769121
TI  - Morphogenetic concepts of normal and abnormal growth in the human prostate.
AB  - Benign prostatic hyperplasia (BPH) and prostate cancer are multifactorial disease
      processes, involving a growing number of biochemical, genetic and epigenetic
      factors. Their pathogenesis, however, remains poorly understood. The present
      review examines current morphogenetic concepts of normal and abnormal growth in
      the human prostate. This includes the role of basal cells in organogenesis and
      cancerogenesis, the impact of cell-matrix interactions, and the importance of
      cellular heterogeneity in tumour progression and hormone-insensitive growth.
      Knowledge of morphogenesis and morphology is required in any scientific approach
      to BPH and prostate cancer.

PMID- 9769122
TI  - Primary hereditary medullary thyroid carcinoma--C-cell morphology and correlation
      with preoperative calcitonin levels.
AB  - Early thyroidectomy offers an opportunity of preventing the development of
      medullary thyroid carcinoma (MTC) in patients at risk for hereditary MTC. We
      investigated the thyroid glands of 32 patients with hereditary MTC to identify
      the changes in C-cell morphology and to correlate these with plasma calcitonin
      (CT) levels and with clinical data. The entire thyroid gland was processed for
      histological examination including immunostaining for CT. All glands revealed C
      cell hyperplasia (CCH), and MTC was found in 21 patients (66% of 32, youngest
      patient 6 years, youngest with lymph node metastases [LNM] 17 years). The
      transition from CCH to MTC was characterized by destruction of the follicular
      basement membrane and by diminished intensity of CT immunostaining. Normal plasma
      CT levels after provocation with pentagastrin were found only in patients with
      CCH. Basally elevated plasma CT levels were restricted to MTC. LNM were only
      found in multifocal tumours at least 4 mm in diameter. It is not yet clear
      whether or not CCH in patients at risk for hereditary MTC is a neoplastic change,
      but in these patients the term 'C-cell hyperplasia' is of doubtful value. All MEN
      gene carriers reveal CCH, and almost all of them will develop multifocal MTC, so
      that CCH is probably a precursor lesion of an indubitably malignant tumour.
      Prophylactic thyroidectomy is justified at the age of 6 to anticipate development
      of a MTC. Lymphadenectomy is necessary in children if they are older than 10
      years or have elevated plasma CT levels.

PMID- 9769123
TI  - "Atypical" medullary thyroid carcinoma with little or no calcitonin expression.
AB  - In a retrospective analysis of 142 medullary thyroid carcinomas, four sporadic
      cases with an unusual histological and immunohistochemical appearance were found.
      Three cases (two males, one female) had very few calcitonin-positive tumour
      cells, while the fourth case (male) completely lacked calcitonin immunoreactivity
      at both mRNA and protein levels, whereas a variety of neuroendocrine markers were
      positive in at least 50% of tumour cells. The four tumours were completely devoid
      of carcinoembryonic antigen expression and of amyloid. Differential diagnosis and
      histogenetic considerations are discussed.

PMID- 9769124
TI  - Diagnostic cytological features of neuroendocrine differentiated carcinoma of the
      breast.
AB  - Neuroendocrine (NE) features characterize a minority of carcinomas of the breast
      corresponding to definite subtypes, which cover a wide spectrum of
      differentiation. Breast metastases from NE tumours of gastrointestinal origin are
      not rare, and to determine whether NE carcinomas in the breast could be
      differentiated from other tumours on fine needle aspiration (FNA) we analysed the
      cytological features of 13 primary NE breast carcinomas of different types (7
      carcinoid-like, 5 mucinous and 1 solid spindle cell). Smears of carcinoid-like
      carcinomas showed specific features that made it possible to differentiate them
      from other primary tumours, but not from breast metastases of NE carcinomas.
      These features were: cell clusters with rigid borders, single cells with a
      plasmacytoid appearance and peripheral cytoplasmic granules evident on Giemsa
      staining and immunoreactive for chromogranin A. In mucinous NE carcinomas such
      granules were less apparent, and the cytological features could have been
      mistaken for those of fibroadenomas, as in the case of non-NE mucinous
      carcinomas. The solid spindle cell type showed noncohesive fusiform cells and
      moderate nuclear pleomorphism, a pattern similar to that of atypical carcinoids
      of the lung.

PMID- 9769125
TI  - Expression of cyclin Ds in relation to p53 status in human breast carcinomas.
AB  - Cyclin D1 has been reported to be overexpressed in many tumours, including breast
      carcinomas. Cyclin D1 was first identified as a protooncogene (BCL1/PRAD1), and
      its overexpression was related to tumour proliferation. The product has also
      recently been identified as important in mediating cell cycle growth arrest via
      the p53 pathway in murin fibroblast cell lines. Ninety breast carcinomas
      previously analysed for p53 status were analysed for amplification of cyclin D1,
      D2 and D3 genes by Southern blot analysis and for protein expression by
      immunhistochemistry. In 10 samples gene amplification was detected at the cyclin
      D1 locus. No gene amplification was detected at the cyclin D2 and D3 loci.
      Immunoreactivity for cyclin D1 was detected in 38 (42.2%) tumour tissue samples.
      Fifty samples were immunostained for cyclin D2 and D3. Only 2 samples (4%) showed
      immunoreactivty for cyclin D2, and 9 samples (18%) for cyclin D3. Cyclin D1
      protein overexpression was significantly more often found in tumours with wild
      type p53 and in tumours with higher grades of differentiation expressing ER. No
      association was seen between gene amplification of the cyclin D1 gene and p53
      status. We conclude there is a relationship between wild type p53 and cyclin D1
      protein overexpression in clinical material, indicating that cyclin D1 may be
      another downstream effector of p53.

PMID- 9769126
TI  - Bcl-2 expression in male breast carcinoma.
AB  - We have analysed the expression of bcl-2 protein retrospectively in 34 primary
      male breast carcinomas (MBC), using the monoclonal antibody bcl-2 in formalin
      fixed, paraffin-embedded tissues. Bcl-2 expression was compared with tumour
      clinicopathological features, sex steroid hormone receptors, DNA content, p53
      immunoreactivity and cell proliferative activity assessed by counts of the
      argyrophilic nucleolar organizer regions (AgNORs), the monoclonal antibody PC10
      against proliferating cell nuclear antigen and the monoclonal antibody MIB-1.
      Most (28, or 82.3%) of the 34 cases of MBC were bcl-2 positive. No association
      was found with clinicopathological features of the tumours, although bcl-2 tended
      to be more frequently expressed in small tumours (P=0.09) and in cases without
      necrotic areas (P=0.1). Nor was any association found with hormone receptor
      status, p53 immunoreactivity, DNA content, cell proliferative activity or patient
      survival. In multivariate analysis, only proliferative activity (expressed by
      AgNOR counts) and p53 immunoreactivity had independent prognostic significance.
      Our results indicate that MBC differs from FBC in that in MBC bcl-2 protein is
      not related to an oestrogen-dependent transcription pathway and bcl-2 alone is
      not sufficient to induce increased proliferation. These characteristics, together
      with the high prognostic value of cell proliferation and the lack of prognostic
      significance for hormone receptor status, support the hypothesis that MBC is
      biologically different from FBC.

PMID- 9769127
TI  - The retroperitoneal resection margin and vessel involvement are important factors
      determining survival after pancreaticoduodenectomy for ductal adenocarcinoma of
      the head of the pancreas.
AB  - The prognosis of ductal adenocarcinoma of the pancreas is still poor. We analysed
      the factors that have a major influence on the survival of patients. Surgical
      specimens from 51 patients with ductal adenocarcinoma of the head of the pancreas
      were examined for tumour size, histological type, grade and local extension. In 7
      patients the retroperitoneal resection margin was involved either macroscopically
      or histologically. Their mean survival was 10.6 months (1-17 months), compared
      with 22.7 months for the 44 patients with curative R0 resection. In 10 patients
      large vessels (portal and/or mesenteric vein) had to be resected; they survived
      for only 2-11 months, with a mean of 5 months (P<0.05). Non-R0-resected patients
      and patients in whom tumour-invaded vessels had to be resected constitute a high
      risk group with a significantly shorter mean survival of 8.8 months, compared
      with 24.3 months for R0 resected patients without vessel invasion (P<0.05). Lymph
      node metastases were seen in 35 of 51 patients. Survival analysis based on nodal
      status revealed a mean survival of 33 months for patients staged as N0, 21.4 for
      N1a patients and 14 month for N1b patients. The differences were not
      statistically significant, however. Our data suggest that tumour invasion of the
      retroperitoneal resection margin and large vessel involvement are the major
      factors determining survival in patients with pancreatic cancer.

PMID- 9769128
TI  - TPA-induced cohort migration of well-differentiated human rectal adenocarcinoma
      cells: cells move in a RGD-dependent manner on fibronectin produced by cells, and
      phosphorylation of E-cadherin/catenin complex is induced independently of cell
      extracellular matrix interactions.
AB  - We have already presented a two-dimensional cell motility assay using a highly
      metastatic variant (L-10) of human rectal adenocarcinoma cell line RCM-1 as a
      motility model of tumour cells of epithelial origin. In this model, L-10 cells
      showed locomotion as a coherent sheet when stimulated with 12-O
      tetradecanoylphorbol-13-acetate (TPA), and we called this type of movement
      "cohort migration". Electron and immunoelectron microscopic study of the
      migrating cell sheets demonstrated localized release from cell-cell adhesion only
      at the lower portion of the cells with loss of E-cadherin immunoreactivity, and
      this change was associated with increased tyrosine phosphorylation of the E
      cadherin-catenin complex, including beta-catenin. Cell-extracellular matrix (ECM)
      interactions involved in this TPA-induced cohort migration and their effect on
      tyrosine phosphorylation of the E-cadherin-catenin complex have now been
      investigated. L-10 cell cohort migration was almost completely inhibited by
      addition of Arg-Gly-Asp (RGD) peptide into the medium, and thus RGD dependent.
      Cohort migration was stimulated on type I and IV collagens, fibronectin (FN)- and
      laminin-coated substratum, but was inhibited by RGD only on FN-coated surface. By
      using immunofluorescent techniques, FN was demonstrated preferentially around
      migrating cells, and a protein synthesis inhibitor, cycloheximide, inhibited the
      migration by about 75%. FN produced by L-10 cells were found to be mostly EDA+ FN
      when analysed by RT-PCR. Moreover, anti-FN antibody, but not anti-vitronectin
      antibody, inhibited the TPA-induced cohort migration almost completely. Thus, it
      was likely that L-10 cells produced FN themselves and moved on the FN substrate
      in an RGD-dependent manner. However, stimulation of migration by type I collagen
      coating and inhibition by RGD treatment did not affect the tyrosine
      phosphorylation of the E-cadherin-catenin complex induced by TPA, indicating that
      cell-cell interactions were adjusted to suit cell migration, irrespective of the
      condition of cell-ECM adhesion, during TPA-induced cohort migration.

PMID- 9769129
TI  - Cell-type- and tumour-type-related patterns of bcl-2 reactivity in mesenchymal
      cells and soft tissue tumours.
AB  - Bcl-2 is one of the many proteins that regulate programmed cell death and is
      overexpressed in B-cell lymphomas. The expression of bcl-2 in mesenchymal cells
      and soft tissue tumours was the subject of this study. Normal mesenchymal tissue
      and representative cases of soft tissue tumours of different types (n>200) were
      investigated immunohistochemically for bcl-2 expression. Although bcl-2
      expression was normally relatively restricted to some smooth muscle cells and
      neural cells, bcl-2 immunoreactivity was widespread in different types of soft
      tissue neoplasms, both benign and malignant. Consistently positive tumours
      included solitary fibrous tumour, haemangiopericytoma, schwannoma and synovial
      sarcoma. The few soft tissue tumours that were consistently negative for bcl-2
      included nodular fasciitis and desmoid tumour. Leiomyomas and leiomyosarcomas
      were heterogeneous; all uterine leiomyomas were bcl-2 positive, but all
      oesophageal leiomyomas were negative, paralleling the reactivity observed in the
      smooth muscle at those sites. Gastrointestinal stromal tumours showed bcl-2
      reactivity; this was less consistent in malignant tumours. Along the malignancy
      gradient, there was no consistent trend in the bcl-2 reactivity.
      Dermatofibrosarcomas showed increase of bcl-2 expression with fibrosarcomatous
      transformation, whereas smooth muscle sarcomas and malignant peripheral nerve
      sheath sarcomas were less consistently positive than the corresponding benign
      neoplasms. We conclude that bcl-2 expression is widespread in soft tissue
      tumours, but shows constitutional expression patterns that are often parallel to
      the normal tissue counterparts. Compared with benign soft tissue tumours, bcl-2
      expression is often reduced in sarcomas, but it cannot be used as a prognostic
      marker without correlation of the data to its phenotypic expression patterns.

PMID- 9769130
TI  - Prognostic significance of standardized AgNOR analysis in early and advanced
      gastric carcinomas.
AB  - To assess the prognostic significance of silver-stained nucleolar organizer
      region (AgNOR) proteins, a standardized AgNOR analysis was performed on 78
      patients affected by early (EGC, n=24) or advanced (AGC, n=54) gastric
      carcinomas. The histopathological diagnosis, grading and staging were done
      according to WHO and UICC recommendations; the mean follow-up time was 56.9
      months. Visualization and quantification of AgNORs were made in formalin-fixed,
      paraffin-embedded sections as specified in the guidelines of the Committee on
      AgNOR Quantification (1995). Statistical analysis was performed on the mean AgNOR
      area values (NORA). Highly significant differences (P<0.001) were found in NORA
      values between EGC and AGC, between low- and high-grade gastric carcinomas and
      between patients dead from gastric cancer and living patients. In addition,
      significant P values were found on comparison of NORA values relating to pT
      status, pN status and stage. Comparison of Kaplan-Meier survival curves revealed
      that patients affected by gastric carcinomas with higher NORA values (>5.213
      microm2) had a worse prognosis. Finally, using Cox multiple regression analysis,
      the AgNOR quantity emerged as a useful independent prognostic variable to predict
      the final outcome of patients affected by EGC or AGC.

PMID- 9769131
TI  - Identification of mitochondria in liver biopsies. A study by
      immunohistochemistry, immunogold and Western blot analysis.
AB  - Hepatocytes are rich in mitochondria, which play an important role in hepatic
      metabolism. In certain pathologic conditions (most often alcoholic liver disease)
      mitochondria became enlarged; nevertheless, even in these conditions they are
      hardly detectable on light microscopy. Recently an antimitochondrial antibody
      (mAM), which recognizes a 60-kDa protein, has been characterized. The purpose of
      the present study was to study immunoreactivity of this antibody in a series of
      liver biopsies. We studied 146 liver biopsies using an mAM. In 8 cases an
      ultrastructural study was also done, and in 2 cases Western blot analysis was
      performed. Cases were divided as follows: alcoholic liver disease (ALD, 31);
      steatosis (8); nonalcoholic steatohepatitis (NASH, 1); hepatitis C virus (HCV)
      related hepatitis (83); hepatitis B virus (HBV)-related hepatitis (6); primary
      biliary cirrhosis (1); sclerosing cholangitis (1); haemosiderosis (1);
      sarcoidosis (1); alpha-1-antitrypsin deficiency (1); nonspecific findings (12).
      All the patients were investigated for alcohol or drug abuse, pharmacological
      treatment, hyperlipidaemia, hypercholesterolaemia and diabetes. Immunoreactivity
      was diffuse in cases of ALD, NASH and steatosis, and in patients with drug abuse.
      Electron microscopic immunogold and Western blot analysis confirmed that in the
      conditions examined the protein recognized by the mAM showed greater expression.
      Immunohistochemical staining was helpful in demonstrating a toxic or a metabolic
      insult even in cases in which the histological picture was blurred by viral
      infection.

PMID- 9769132
TI  - Regulation of apoptotic cell death in the pyloric glands of the canine stomach.
AB  - In gastrointestinal epithelia, apoptosis has been thought to play a part in the
      shedding of postmitotic cells into the lumen. However, we have found that
      apoptosis more frequently in the generative cell (G) zone (the lower one third of
      the pit) than in the luminal zone (the upper one third of the pit) and the gland
      zone in the canine pyloric gland. To analyse the regulation of apoptotic cell
      death in each zone, we labelled S-phase cells by single and repeated injections
      of bromodeoxyuridine (BrdU) i.v. at intervals of 8 h. We found that 30% of
      apoptoses in the G zone were flash-labelled by BrdU and might derive from cells
      in or just after the S phase. The incidence of apoptosis and mitotic index did
      not change significantly after repeated injections of BrdU until the 49-h point,
      when the incidence of apoptosis increased and the mitotic index decreased
      significantly in the G zone, while the incidence of apoptosis decreased in the
      luminal zone. The BrdU-induced increase of apoptosis and cell-cycle arrest at the
      49-h point may be caused by enhanced DNA mispairs that are elicited by
      incorporation of BrdU, in particular using the template of BrdU incorporated DNA.
      Apoptosis in the luminal zone may be down-regulated by reduced cell production in
      the G-zone.

PMID- 9769133
TI  - Adenocarcinoma in an ileal pouch after prior proctocolectomy for carcinoma in a
      patient with ulcerative pancolitis.
AB  - We report the first known case of pouch carcinoma in a 35-year-old female patient
      following proctocolectomy for adenocarcinoma in ulcerative pancolitis with
      backwash ileitis. Pouch cancer was diagnosed 2 years after the pelvic pouch
      procedure, illustrating that there might be a risk of pouch cancer in such
      patients. Adenocarcinoma arising in an ileoanal reservoir is rare. Two other
      cases have been reported: both patients concerned were believed to have developed
      cancer in small areas of residual remaining rectal mucosa.

PMID- 9769134
TI  - Are adenomyoepithelioma of the breast and epithelial-myoepithelial carcinoma of
      the salivary glands identical tumours?

PMID- 9769135
TI  - Trends in infant mortality attributable to birth defects--United States, 1980
      1995.
AB  - Infant mortality has declined in the United States because of advances in public
      health and clinical medicine. Birth defects are the leading cause of infant
      mortality, but infant mortality attributable to birth defects (IMBD) has not
      declined as rapidly as overall infant mortality. From 1968 to 1995, the
      proportion of IMBD increased from 14.5% to 22.2%. To help focus efforts to reduce
      IMBD, CDC examined trends in IMBD, highlighting demographic, geographic, and
      defect-specific mortality rates. This report summarizes the results of this
      analysis, which indicate variation in rates for IMBD by sex, race/ethnicity, and
      state of residence.

PMID- 9769136
TI  - Progress toward poliomyelitis eradication--India, 1998.
AB  - In 1988, the World Health Assembly resolved to eradicate poliomyelitis globally
      by 2000. In 1995, India began to accelerate implementation of polio eradication
      strategies by conducting annual National Immunization Days (NIDs). In 1997, an
      active surveillance system for polio using acute flaccid paralysis (AFP) as a
      screening case definition was established. This report summarizes progress toward
      polio eradication, focusing on the implementation of supplemental vaccination
      activities and the establishment of sensitive surveillance. The findings suggest
      that NIDs in India have decreased previously widespread poliovirus circulation.

PMID- 9769137
TI  - Incidence of foodborne illnesses--FoodNet, 1997.
AB  - Each year, millions of persons become ill from foodborne diseases, though many
      cases are not reported. The Foodborne Diseases Active Surveillance Network (Food
      Net), the primary foodborne diseases component of CDC's Emerging Infections
      Program, was developed to better characterize, understand, and respond to
      foodborne illnesses in the United States. This report describes FoodNet
      surveillance data from 1997, the second year of surveillance, and compares
      findings with data from 1996. The findings demonstrate regional and seasonal
      differences in the reported incidence of certain bacterial and parasitic diseases
      and that substantial changes occurred in the incidence of illnesses caused by
      some pathogens (e.g., Vibrio and Escherichia coli O157:H7) but the overall
      incidence of illness caused by the seven diseases under surveillance in both
      years changed little.

PMID- 9769138
TI  - Lymphoid cell-growth hormone interactions: a serum-free model.

PMID- 9769139
TI  - Crystallization of neutral red vital stain from minimum essential medium due to
      pH instability.

PMID- 9769140
TI  - Strain-induced dual alignment of L6 rat skeletal muscle cells.

PMID- 9769141
TI  - Characterization of NR10(2) macrophages.

PMID- 9769142
TI  - Matrix mRNA levels in ligament tissue versus cells.

PMID- 9769143
TI  - Polyamine as a growth promoter for cultured insect cells.

PMID- 9769144
TI  - Primary culture of colonocytes in rotating bioreactor.

PMID- 9769145
TI  - The motile behavior of human breast cancer cells characterized by time-lapse
      videomicroscopy.

PMID- 9769146
TI  - Culture of mosquito cells in Eagle's medium.

PMID- 9769147
TI  - Acute cytotoxicity testing with cultured human lung and dermal cells.
AB  - An extensive in vitro study with cultured cells was conducted to test the basal
      cytotoxicity theory. This theory suggests that most chemical injury, at least in
      vitro, is a manifestation of one or more insults to the basic cellular structures
      and functions common to mammalian cells. This accounts for the similarity of
      results in multilaboratory studies. Human fetal lung fibroblasts (HFL1), and
      human skin fibroblasts (WS1, Detroit551) were studied in culture to evaluate
      their potential to screen for cytotoxicity. Confluent monolayers were incubated
      in the absence or presence of increasing concentrations of test chemicals for 24
      h, and the MTT assay was used to assess toxicity. Inhibitory concentrations were
      extrapolated from concentration-effect curves after linear regression analysis.
      Twenty-nine chemicals were tested with each cell line and the cytotoxicity data
      compared to rodent and human lethal concentrations. The data suggest that the
      experimental IC50 values are as accurate predictors of human toxicity as
      equivalent toxic blood concentrations derived from rodent LD50s. In addition,
      lung and skin fibroblasts revealed no significant differences among the three
      cell lines. The results support the conclusion that finite cell lines of human
      origin have the potential for screening chemicals for human toxicity. In
      combination with previously published reports, the data suggest that a basal
      cytotoxic phenomenon may explain the similarity of results among different human
      cell lines.

PMID- 9769148
TI  - Organotypic culture of human ovarian surface epithelial cells: a potential model
      for ovarian carcinogenesis.
AB  - The objective of this work was to establish an in vitro multidimensional culture
      system for human ovarian surface epithelial (HOSE) cells as a model for ovarian
      carcinogenesis. The epithelial origin of cell outgrowth from cells obtained from
      the ovarian surface was confirmed by keratin staining. Two cultures from two
      different patients were established, HOSE-A and HOSE-B. Cultures were infected
      with a retrovirus expressing human papillomavirus genes E6 and E7 to extend their
      life span. HOSE cells were seeded onto collagen gels containing NIH3T3-J2
      fibroblasts as feeder cells and grown to confluence submerged in growth medium.
      The collagen bed was then raised to the air-medium interface for 7 d (organotypic
      culture). Microscopically, fixed cultures revealed a single layer of flat cells
      growing on the collagen surface, reminiscent of HOSE cells in vivo. Infected HOSE
      A and HOSE-B cells exhibited aberrant growth because they stratified. In
      addition, established ovarian cancer lines grown in this fashion stratified and
      showed malignant phenotypes. Thus, cells grown in organotypic culture resemble
      their in vivo counterparts, providing a basis for establishing a system to study
      growth, proliferation, differential gene expression, and perhaps malignant
      transformation of HOSE cells.

PMID- 9769149
TI  - Fibroblast movements during contraction of collagen lattices--a quantitative
      study using a new three-dimensional time-lapse technique with phase-contrast
      laser scanning microscopy.
AB  - In this study we assessed the behavior of fibroblasts during contraction of
      collagen lattices. We applied a new technique for three-dimensional time-lapse
      studies of movements of living cells using phase-contrast laser scanning
      microscopy. Five anchored and five floating collagen lattices were studied
      regarding the activity of cells during a 7-h period of active contraction. Three
      dimensional reconstructions of the fibroblasts and their extensions were made
      from datasets of 16-26 "optical sections" 5 microm apart recorded hourly during
      the period of measurements. The distance between fibroblast nuclei in the
      floating lattices decreased by a mean of 6.8 microm, but remained constant in the
      anchored group. Only minor variations were found in the angle between a line
      connecting any two nuclei and the tangent of the lattice margin. The lengths of
      the cellular extensions continuously changed by shortening and extending, and an
      increasing number of intercellular contacts were established with time. The angle
      between the extensions and the periphery of the lattice varied continually, and
      no distinct pattern of arrangement of the extensions was seen. In conclusion, we
      have shown in living cells in vitro that fibroblasts do not appear to move around
      within lattices during contraction but rather send out and withdraw cellular
      extensions continuously. This speaks against cellular locomotion or movement as a
      main feature of contraction. Time-lapse scanning laser microscopy has also been
      shown to be a suitable method to study cellular behavior quantitatively in three
      dimensions during lattice contraction.

PMID- 9769150
TI  - In vitro biosynthesis of juvenile hormone in larval honey bees: comparison of six
      media.
AB  - We have formulated a tissue culture medium based on the components of larval
      honey bee hemolymph. Using an in vitro radiochemical assay to measure juvenile
      hormone biosynthesis, we compared our larval-based medium to four commercially
      available media (Grace's, Medium-199; Shields and Sang M3, and Minimum Essential
      Medium), and a medium based on adult honey bee hemolymph. All media were
      formulated without methionine. There was no significant difference in the amounts
      of juvenile hormone produced by the larval medium and Grace's; both of these
      media, however, were more suitable than the remaining four. Our larval-based
      tissue culture medium should prove useful in studies aimed at elucidating the
      underlying hormonal mechanism(s) of caste development in honey bees.

PMID- 9769151
TI  - BG-1 ovarian cell line: an alternative model for examining estrogen-dependent
      growth in vitro.
AB  - Examination of estrogen-responsive processes in cell culture is used to
      investigate hormonal influence on cancer cell growth and gene expression. Most
      experimental studies have used breast cancer cell lines, in particular MCF7
      cells, to investigate estrogen responsiveness. In this study we examined an
      ovarian cancer cell line, BG-1, which is highly estrogen-responsive in vitro.
      This observation, plus the fact that the cells are of ovarian rather than mammary
      gland origin, makes it an attractive alternative model. 17Beta-estradiol,
      epidermal growth factor, and insulin-like growth factorinduced proliferation of
      BG-1 and MCF7 cells. Viability was dependent on these growth factors in BG-1
      cells, but not in MCF7 cells. Therefore, we examined the differences between
      these two cell lines with respect to estrogen and growth factor receptors. BG-1
      cells have twice as many estrogen receptors as MCF7 cells, and BG-1 cells have
      higher insulin-like growth factor-1 and epidermal growth factor receptor levels
      than MCF7 cells. This may also explain why BG-1 cells proliferate 56% more
      robustly in serum and show more serum dependence in culture. In both BG-1 and
      MCF7 cells, epidermal growth factor receptor number is low (<20000/cell), while
      insulin-like growth factor-1 receptor level was highest in estrogen receptor
      positive cell lines. For example, insulin-like growth factor-1 receptor was
      higher in BG-1 and MCF7 cells than in estrogen receptor negative cells (HeLa >
      MDA-MB-435 > HBL100). In conclusion, BG-1 cells are an excellent model for
      understanding hormone responsiveness in ovarian tissue and an alternative for
      examining estrogen receptor-mediated and insulin-like growth factor-1/epidermal
      growth factor/estrogen cross-talk processes because of their sensitivity to these
      factors.

PMID- 9769152
TI  - Response of preimplantation murine embryos to heat shock as modified by
      developmental stage and glutathione status.
AB  - Objectives were to characterize developmental changes in response to heat shock
      in the preimplantation mouse embryo and to evaluate whether ability to synthesize
      glutathione is important for thermal resistance in mouse embryos. Heat shock (41
      degrees C for 1 or 2 h) was most effective at disrupting development to the
      blastocyst stage when applied to embryos at the 2-cell stage that were delayed in
      development. Effects of heat shock on ability of embryos to undergo hatching were
      similar for 2-cell, 4-cell, and morula stage embryos. The phenomenon of induced
      thermotolerance, for which exposure to a mild heat shock increases resistance to
      a more severe heat shock, depended upon stage of development and whether embryos
      developed in vitro or in vivo. In particular, induced thermotolerance was
      observed for morulae derived from development in vivo but not for 2-cell embryos
      or morulae that developed in culture. Administration of buthionine sulfoximine to
      inhibit glutathione synthesis did not increase thermal sensitivity of 2-cell
      embryos or morulae but did reduce subsequent development of 2-cell embryos at
      both 37 degrees and 41 degrees C. In summary, changes in the ability of 2-cell
      through morula stages to continue to develop following a single heat shock were
      generally minimal. However, 2-cell embryos delayed in development had reduced
      thermal resistance, and therefore, maternal heat stress may be more likely to
      cause mortality of embryos that are already compromised in development. There
      were also developmental changes in the capacity of embryos to undergo induced
      thermotolerance. Glutathione synthesis was important for development of embryos
      but inhibition of glutathione synthesis did not make embryos more susceptible to
      heat shock.

PMID- 9769153
TI  - Factors affecting Caco-2 intestinal epithelial cell interleukin-6 secretion.
AB  - Intestinal epithelial cells (IEC) have previously been shown to produce several
      cytokines including interleukin-6 (IL-6). However, many factors which may
      regulate IL-6 secretion by human IEC still remain a mystery due in part to the
      lack of appropriate model cell lines and the difficulty of culturing human IEC
      over long periods of time. We have determined that the human colonic carcinoma
      cell line Caco-2 is capable of secreting IL-6 when stimulated by the inflammatory
      cytokines IL-1beta or tumor necrosis factor-alpha (TNF-alpha), and stimulation of
      these cells with IL-1beta plus TNF-alpha induced a synergistic enhancement of IL
      6 secretion. The inflammatory cytokine-induced enhancement in IL-6 secretion was
      greatest when the cells were cultured in a 10% CO2 atmosphere as compared to
      cells grown in 5% CO2, suggesting that environmental CO2 levels may affect IEC
      cytokine secretion. Finally, long-term culture of the Caco-2 cells to induce
      cellular differentiation had no effect on the capacity of these cells to produce
      IL-6, indicating that the regulation of IL-6 secretion was not affected by
      differentiation. Taken together, these studies provide important information on
      the factors which regulate IL-6 secretion by human IEC as they may contribute to
      the cytokine network during a mucosal inflammation. The results also suggest that
      the Caco-2 cell line is an appropriate model for further studies on the
      regulation of cytokine secretion by human IEC.

PMID- 9769154
TI  - Immunoreactivity of neural crest-derived cells in thymic tissue developing under
      the rat kidney capsule.
AB  - In order to study the functional development of a thymus in an experimental
      model, small pieces of adult rat thymic tissue were cultured for 9 days and
      implanted under the kidney capsule of littermates. The tissues were examined with
      a panel of antibodies raised against thymic and neural factors and neural crest
      cells at intervals from 5 to 13 days. At 5 days post-implantation, there were
      groups of L1+ cells within the implants that reacted with antibodies raised
      against neural and neural crest cell markers. L1+ cells were highly mitotic,
      rounded cells measuring 8.7 +/- 0.6 micrometer in diameter. Double immunostaining
      with different combinations of antibodies showed that 94% of the L1+ cells were
      also TH+, and many were HNK-1/NCAM+, PGP 9.5+, NGF+, chromogranin A+, VIP+,
      S100+, CGRP+, GAD+, and A2B5+. A few were also pan-cytokeratin+. These results
      indicate that these cells are derived from neural crest derived cells and belong
      to the neuroepithelial line of development. The L1+ cells were most numerous
      before nerves appeared (about Day 9) and reduced in number and extent as the
      thymus differentiated. The neural crest cells occasionally had long cytoplasmic
      extensions, but it was not possible to decide if they formed the nerves that
      appeared in the implants. Adult thymuses also contained a population of L1+ and
      HNK-1/NCAM+ cells, mainly in the subcapsular cortex, the septa, and the medulla.
      These cells could be a source of neural crest cells able to repopulate the
      implant. The adult thymus may always contain a reservoir of cells potentially
      capable of producing neuropeptides and transmitter factors required for thymic
      growth and regeneration.

PMID- 9769155
TI  - Sympathectomy-induced immune changes are not abrogated by the glucocorticoid
      receptor blocker RU-486.
AB  - Removal of sympathetic noradrenergic input to the immune system by injection of 6
      hydroxydopamine (6-OHDA) triggers increases in antigen-specific in vitro
      splenocyte proliferation and cytokine production in BALB/cJ and C57B1/6J mice.
      This examines the possible role of glucocorticoids in these previously reported
      changes. In both strains, chemical sympathectomy triggers an elevation of
      glucocorticoid levels immediately following injection of 6-OHDA, returning to
      normal within one to two days. In the BALB/cJ strain, glucocorticoid elevation is
      seen only after the initial 6-OHDA injection; levels in chronically denervated
      animals are not different from controls. In the C57B1/6J strain, the increase is
      seen even with chronically denervated animals. Prior implantation of mice with
      pellets containing the glucocorticoid receptor antagonist RU-486 does not
      abrogate denervation-induced increases in cytokine production or proliferation in
      either strain. In addition to the previously reported increased interleukin (IL)
      2 and IL-4 production, there is an increase in IFN-gamma production in the
      C57B1/6J strain following either acute or chronic denervation. The persistence of
      denervation-induced changes even when the effect of corticosterone is blocked
      with RU-486 or diminished with chronic denervation indicates that the changes are
      driven mainly by a glucocorticoid-independent mechanism.

PMID- 9769156
TI  - IL-6 knock-out mice show modified basal immune functions, but normal immune
      responses to stress.
AB  - To better determine the role of interleukin-6 in the mechanisms that regulate
      stress-induced immunosuppression, we used in this study an interleukin-6
      deficient mice model recently generated by gene targeting. We report here that,
      in basal conditions, mutant mice are characterized by altered immune functions.
      Natural killer activity and interleukin-2 production are lower in splenocytes of
      interleukin-6 deficient mice compared to those of controls, whereas Concanavalin
      A-induced splenocyte proliferation is comparable with that observed in wild-type
      mice. Moreover, splenocyte concentrations of the immunosuppressive opioid peptide
      beta-endorphin are higher in interleukin-6 deficient mice while serum
      corticosterone concentrations are unchanged. After exposure to 16 h of restraint
      stress, a significant suppression of the immune parameters is exhibited and a
      significant increase of splenocyte beta-endorphin concentrations are present in
      knock-out and normal animals. Finally, corticosterone is normally induced in
      stressed interleukin-6-deficient mice, thus demonstrating that interleukin-6 is
      not crucial for the activation of the hypothalamic-pituitary-adrenal axis. In
      conclusion, our results indicate that interleukin-6 is not a key factor in the
      immunosuppression observed after restraint stress.

PMID- 9769157
TI  - Selective effects of peripheral lipopolysaccharide administration on contextual
      and auditory-cue fear conditioning.
AB  - The reported experiments explore the effects of peripheral LPS administration on
      learning and memory processes. As measured by the conditioned freezing response,
      intraperitoneal LPS administration given after conditioning impaired contextual
      but not auditory-cue fear conditioning in both juvenile (hooded Long Evans) and
      adult rats (albino Sprague Dawley) of two different strains. This impairment in
      contextual fear conditioning was not dependent on the presence of the tone.
      Preexposure to the context eliminated the effect of LPS on contextual fear
      conditioning, and in addition, LPS given after context preexposure negated the
      beneficial effects of preexposure on contextual fear. These results suggest that
      LPS disrupts posttrial memory consolidation processes. In support of the
      hypothesis that LPS-induced proinflammatory cytokine release is involved in
      producing the impairment in contextual fear caused by LPS, peripheral interleukin
      1 receptor antagonist (IL-1ra) administered subcutaneously at a dose of 100 mg/kg
      prevented the impairment in contextual fear caused by LPS. These experiments
      provide evidence for a role of immune activation and cytokine activity in
      learning and memory processes.

PMID- 9769158
TI  - Central nervous system activation following peripheral chemical sympathectomy:
      implications for neural-immune interactions.
AB  - Many studies have demonstrated that ablation of the sympathetic nervous system
      (SNS) alters subsequent immune responses. Researchers have presumed that the
      altered immune responses are predominantly the result of the peripheral
      phenomenon of denervation. We, however, hypothesized that chemical sympathectomy
      will signal and activate the central nervous system (CNS). Activation of the CNS
      was determined by immunocytochemical visualization of Fos protein in brains from
      male C57BL/6 mice at 8, 24, and 48 h following denervation. A dramatic induction
      of Fos protein was found in the paraventricular nucleus (PVN) of the hypothalamus
      and other specific brain regions at 8 and 24 h compared to vehicle control mice.
      Dual-antigen labeling demonstrates that corticotrophin releasing factor (CRF)
      containing neurons in the PVN are activated by chemical sympathectomy; however,
      neurons containing neurotransmitters which may modulate CRF neurons, such as
      vasopressin, tyrosine hydroxylase, and adrenocorticotropin, do not coexpress Fos.
      Our findings suggest an involvement of the CNS in sympathectomy-induced
      alterations of immunity.

PMID- 9769159
TI  - Human brain-immune relationships: a PET study.
AB  - To study brain-immune relations, we correlated positron emission tomographic
      (PET) measures of regional cerebral blood flow (rCBF) with immune measures in 10
      female volunteers. The natural killer (NK) activity correlated negatively with
      activity bilaterally in the secondary sensory cortex, whereas the Concanavalin A
      (Con A) response correlated positively with rCBF bilaterally in secondary visual,
      motor, and sensory cortices, the thalamus, the putamen, and the left hippocampus.
      Although representing preliminary data from a small number of subjects, these
      observations provide further support for the presence of interactions between the
      brain and the immune system.

PMID- 9769160
TI  - Effects of cell concentration on viability and metabolic activity during
      cryopreservation.
AB  - Increasing the cell concentration during the cryopreservation of red blood cells
      (RBC) increased hemolysis. Similarly, increasing the cell concentration during
      the cryopreservation of hepatocytes reduced both the viability of the cells as
      assessed by trypan blue exclusion and the metabolic activity of the trypan blue
      excluding cells. In both cell types, significant damage appeared at cell
      concentration levels exceeding 60%. With tightly packed RBC, hemolysis reached
      63%, while for hepatocytes after thawing and dilution, trypan blue viability was
      reduced to 41% of that of the cells initially isolated. The viability of
      cryopreserved hepatocytes, estimated by trypan blue exclusion, was considerably
      reduced following incubation for 1 h at 37 degrees C and the extent of this
      reduction was also a function of cell concentration during freezing and thawing.
      The trypan blue viability of hepatocytes that were tightly packed during
      cryopreservation and then incubated at a concentration of 5 x 10(6) viable
      cells/ml fell dramatically to only 12.5%. The protein-synthesizing activity and
      the membrane transport activity of these cells, expressed in terms of cells that
      excluded trypan blue immediately following thawing and removal of the
      cryoprotectant, were reduced to 38.7 and 33.5%, respectively, of the activity in
      cells that were packed at 10% cell concentration. The fall in metabolic activity
      may have been due to complete loss of activity in some of the cells or reduced
      activity in most or all of the cells or any combination of these factors. It is
      concluded that there may be many mechanisms involved, but the most important
      factor is probably stresses produced by unphysiological cell-cell contacts
      occurring during the freeze-thaw cycle.

PMID- 9769161
TI  - Cryopreservation of pancreatic islets prior to transplantation: a comparison
      between UW solution and RPMI culture medium.
AB  - Effective cryopreservation of pancreatic islets would be valuable in several
      contexts: for the assessment of islet cell viability, the measurement of beta
      cell function, and the maintenance of viability and sterility prior to islet
      transplantation. In this study, isolated rat islets were cryopreserved or not
      following overnight culture and the most suitable preservation solution for
      transportation between centers was sought. Unfrozen and frozen-and-thawed islets
      were allocated to each of four different groups: untreated controls; cultured
      overnight in RPMI at 37 degrees C; cold stored at 4 degrees C in RPMI for 18-24
      h; and stored at 4 degrees C in University of Wisconsin (UW) solution for 18-24
      h. The greatest cell viability, as assessed by ethidium bromide/acridine orange
      staining and image analysis, was observed when postthawed islets were cultured in
      RPMI, whereas the least viable samples were those that were stored in UW
      solution. Measurement of insulin content and secretion in static incubation
      assays using 2.8 and 16.7 mM glucose showed that all treated groups exhibited a
      significant insulin secretory response to glucose stimulation whereas the
      untreated frozen-thawed islets failed to show any response. The cryopreserved
      islets in each group were equally successful in reversing hyperglycemia in
      streptozotocin-treated allogeneic rats when grafted intraportally in sufficient
      numbers (2000-2500). The groups also showed a similar mean graft survival time of
      6-7 days before rejection. However, the best experimental group (the postthaw
      cultured islets) failed to cure diabetic rats when grafted in a smaller numbers
      (<2000). These data demonstrate prompt and sustained function in cryopreserved
      islets when they were maintained by any of the methods studied if they were
      grafted in sufficient numbers. We conclude that cold storage of thawed
      cryopreserved islets using either RPMI or UW solution is an effective method for
      their transportation and/or storage, but does not reduce their immunogenicity
      before transplantation.

PMID- 9769162
TI  - Crystallization of ice in aqueous solutions of glycerol and dimethyl sulfoxide 2:
      ice crystal growth kinetics.
AB  - The crystallization of ice in aqueous solutions of glycerol and dimethyl
      sulfoxide (Me2SO) has been studied using a combined DSC-video microscope
      technique. The solutions investigated were 50w/w% glycerol and 45w/w% Me2SO; both
      of these solutions have a solute concentration of approximately 16 mol%. The
      rates of growth of the external surfaces of ice crystals from both of these
      solutions were determined over broad temperature ranges. The growth rates were
      found to be generally independent of time, particularly at lower temperatures.
      The ice crystal growth rate in the glycerol solution became negligible at a
      significantly higher temperature than in the Me2SO solution. Addition of anti
      freeze protein from the winter flounder at concentrations of 1.7 and 9.9 mg g-1
      was found to have no significant effect on the ice crystal growth rates in 50w/w%
      glycerol solutions.

PMID- 9769163
TI  - Trehalose-mediated protection of the plasma membrane H+-ATPase from Kluyveromyces
      lactis during freeze-drying and rehydration.
AB  - During freeze-drying and rehydration, the activity of the H+-ATPase from the
      plasma membrane of Kluyveromyces lactis was preserved by increasing
      concentrations of carbohydrates. When the H+-ATPase was freeze-dried in the
      absence of carbohydrates the activity was lost. The protective efficiency of
      carbohydrates was as follows: trehalose > maltose > sucrose > glucose >
      galactose. Each carbohydrate exhibited the maximal protection at a concentration
      of 20 mg carbohydrate per milligram of protein or above. No structural changes of
      the rehydrated H+-ATPase were detected by intrinsic fluorescence measurements.
      Trehalose, at 20 mg/mg protein, protected the enzyme activity completely during
      freeze-drying and rehydration. Rehydration temperature was critical; at 20
      degrees C or below, activity was fully retained, while at 30, 40, or 50 degrees C
      activity decreased in proportion with temperature. The trehalose-protected freeze
      dried H+-ATPase was stored at different temperatures for up to 60 days. Storage
      at 4 degrees C resulted in retention of most of the enzymatic activity, while
      storage at 20 or 30 degrees C resulted in loss of activity. The protection of the
      H+-ATPase by trehalose suggests that this carbohydrate might protect other
      membrane enzymes from inactivation during handling.

PMID- 9769164
TI  - Production of monozygotic twins after freezing and thawing of bisected mouse
      embryos.
AB  - We examined the viability of mouse bisected embryos after freezing and thawing
      and produced monozygotic twin mice from these embryos. Two-cell embryos were
      collected from superovulated mature agouti, F1 hybrid (C57BL/6 x CBA) female
      mice. For bisection, one blastomere of the embryo was aspirated with a
      micropipette and injected into an empty zona pellucida. After culture for 24 to
      28 h to the compacted 4- to 8-cell stage or 48 to 52 h to the late morula to
      blastocyst stage, the embryos were slowly frozen (-0.5 to -1.0 degrees C/min),
      thawed (30 degrees C/min), cultured for 24 h, and then transferred to recipient
      females. The bisected embryos without zonae pellucidae had developmental ability
      in vitro similar to those with zonae pellucidae (88% vs 89%). However, after
      freezing and thawing at the compacted 4- to 8-cell stage, bisected embryos with
      zonae pellucidae had higher viability than those without (60% vs 15%). Zona
      enclosed, bisected embryos frozen at the compacted 4- to 8-cell stage were more
      resistnat to freezing and thawing than those at the late morula to blastocyte
      stage (60% vs 23%). After transfer to recipients 26% of the zona enclosed
      bisected embryos frozen-thawed at the 4- to 8-cell stage developed to living
      fetuses a day 17.5 to 18.0 of pregnancy, which was slightly but not significantly
      lower than that of fresh bisected embryos (48%). On the other hand, only 5% of
      bisected embryos frozen-thawed at the late morula to blastocyst stage developed
      to young. The transfer of 15 sets of twin blastocysts as pairs that had been
      frozen and thawed at the compacted 4- to 8-cell stage yielded 2 (13%) sets of
      monozygotic twins.

PMID- 9769165
TI  - Hibernation induces expression of moesin in intestinal epithelial cells.
AB  - Identification of proteins that are differentially expressed in mammals that
      hibernate can provide insight into mechanisms that preserve cellular function at
      low temperatures. A candidate protein was identified in intestinal brush border
      membranes of 13-lined ground squirrels. Intestinal brush border membrane proteins
      were separated using SDS-PAGE and gels were stained with Coomassie blue. We
      observed a approximately 75-kDa band that was specifically increased in brush
      border membranes isolated from torpid squirrels compared with summer active
      squirrels. The 75-kDa band was cut from one-dimensional gels and sequenced. A 17
      amino acid sequence was identified of which amino acids 2-17 matched exactly a
      portion of moesin, a membrane-cytoskeletal linking protein and member of the ERM
      (ezrin/radixin/moesin) family. The sequence results were confirmed using anti
      moesin antibodies that detected strong bands at approximately 75 kDa on Western
      blots of brush border membranes in torpid squirrels (Tb approximately 7 degreesC)
      and only faint signals in summer squirrels (Tb approximately 37 degrees C) or
      aroused hibernators (Tb approximately 37 degrees C). In contrast, signals
      obtained using anti-ezrin antibodies were uniformly strong in all squirrels,
      regardless of activity state. Intestinal brush borders of mice and rats expressed
      ezrin but not moesin. These results provide evidence for the physiological
      induction of an ERM protein in intestinal epithelial cells of torpid hibernators
      and support the idea that hibernation involves differential expression of gene
      products that may facilitate viability of cells at low temperatures.

PMID- 9769166
TI  - Cryopreservation of spermatozoa from freeze-tolerant and -intolerant anurans.
AB  - Spermatozoa of the freeze-tolerant wood frog (Rana sylvatica) were used to
      develop a general protocol for the frozen storage of amphibian spermatozoa.
      Tolerance of spermatozoa to cryoprotective agents and freezing in suspension (-80
      degrees C) was determined from rates of sperm lysis and dual-fluorochrome vital
      dye assays. We tested the efficacy of four cryoprotectants (Me2SO, methanol,
      glycerol, and ethylene glycol), two supplements (fetal bovine serum or
      glutathione), and combinations of these cryoprotectants and supplements. Me2SO
      and fetal bovine serum were the most effective cryoprotectant and supplement,
      respectively, in reducing sperm lysis. Vital dye assays showed that viability was
      greatest for spermatozoa treated with both Me2SO and fetal bovine serum. Thus,
      this combination was used to cryopreserve spermatozoa from the freeze-intolerant
      anurans, Rana pipiens and Bufo americanus. Recovery of viable spermatozoa was
      significantly greater for R. sylvatica (mean +/- SE = 81.2 +/- 9.6%) than for R.
      pipiens (59.0 +/- 2.8%) and B. americanus (47.8 +/- 4.1%), perhaps owing to
      inherent factors promoting its freeze tolerance. Nonetheless, our results support
      the feasibility of using gamete cryopreservation techniques in programs aimed at
      the captive propagation of amphibians.

PMID- 9769167
TI  - Respiratory responses to chilling and freezing in two sub-antarctic insects.
AB  - The effects of chilling (to temperatures above the supercooling point, SCP) and
      freezing on respiration of adults and larvae of two coleopterans living on sub
      Antarctic South Georgia (54 degrees S, 37 degrees W), Hydromedion sparsutum and
      Perimylops antarcticus (Coleoptera, Perimylopidae), were quantified. Respiration
      rates of individual insects (live weights, 11-21 mg) were measured at 10 degrees
      C prior to chilling (-4 degrees C) or freezing (SCP range -3.8 to -5.3 degrees C)
      and posttreatment. The species possess a small amount of freeze tolerance in both
      adults and larvae. Chilling had no significant effects on respiration rates of P.
      antarcticus and H. sparsutum, although mean levels were depressed by 6-15%.
      Freezing produced considerable enhancement of respiratory activity. Mean values
      increased postfreezing in larvae (+34%) of H. sparsutum and in both larvae (+44%)
      (P < 0.01) and adults (77%) (P < 0.05) of P. antarcticus. Chilling and freezing
      had different effects on respiration rates and P. antarcticus showed the greatest
      metabolic response to freezing.

PMID- 9769168
TI  - Muscle minus myoD.

PMID- 9769169
TI  - A role for nautilus in the differentiation of muscle precursors.
AB  - In the Drosophila embryo, nautilus is expressed in a subset of muscle precursors
      and differentiated fibers and is capable of inducing muscle-specific
      transcription, as well as myogenic transformation. In this study, we examine the
      consequences of nautilus loss-of-function on the development of the somatic
      musculature. Genetic and molecular characterization of two overlapping
      deficiencies, Df(3R)nau-9 and Df(3R)nau-11a4, revealed that both of these
      deficiencies remove the nautilus gene without affecting a common lethal
      complementation group. Individuals transheterozygous for these deficiencies
      survive to adulthood, indicating that nautilus is not an essential gene. These
      embryos are, however, missing a subset of muscle fibers, providing evidence that
      (1) some muscle loss can be tolerated throughout larval development and (2)
      nautilus does play a role in muscle development. Examination of muscle precursors
      in these embryos revealed that nautilus is not required for the formation of
      muscle precursors, but rather plays a role in their differentiation into mature
      muscle fibers. Thus, we suggest that nautilus functions in a subset of muscle
      precursors to implement their specific differentiation programs.

PMID- 9769170
TI  - Somitogenesis controlled by Noggin.
AB  - In vertebrates, the segmented somites, which are the medial-most component in the
      paraxial mesoderm, are the entity giving rise to the axial bones and skeletal
      muscles. We previously demonstrated that the mechanism that distinguishes the
      somite from the more lateral mesoderm (lateral plate) involves different levels
      of BMP-4 activity which is highest in the lateral plate. We report that Noggin,
      an antagonist of BMP-4, is expressed in the presumptive somite and appears to
      control effective levels of BMP-4 to differentiate somitic mesoderm from the
      lateral plate. When Noggin-producing cells were implanted into the presumptive
      lateral plate, they produced ectopic somites that were respecified from the
      lateral plate precursors. These somites exhibited no mediolateral (M-L) polarity,
      but acquired it when implanted Noggin was eliminated. Thus, in normal
      embryogenesis no or low BMP-4 activity realized by Noggin specifies the somites
      in the medial-most portion of the paraxial mesoderm, and then BMP-4 emanating
      from the lateral plate subsequently establishes the M-L polarity in the somites.

PMID- 9769171
TI  - FREAC-1 contains a cell-type-specific transcriptional activation domain and is
      expressed in epithelial-mesenchymal interfaces.
AB  - The forkhead transcription factor FREAC-1 is a potent transcriptional activator.
      We have localized a transcriptional activation domain in the C-terminus of FREAC
      1 and another one to a stretch of approximately 60 amino acids in the central
      part of the protein. While the C-terminal activation domain activates in all cell
      lines tested, the activation domain in the central part of the protein is
      functional only in cell lines derived from lung. This cell-type-specific activity
      is retained when the activation domain is fused to the heterologous DNA binding
      domain of Gal4. The human FREAC-1 gene was found to consist of two exons
      separated by an intron of 1.2 kb. Exon 1 encodes the forkhead DNA binding domain
      and the cell-type-specific activation domain. Exon 2 encodes the general
      activation domain. The distribution of FREAC-1 expression during embryogenesis
      was investigated by in situ hybridization. FREAC-1 mRNA was found in mesenchyme
      in immediate proximity to endodermal epithelia throughout the digestive, urinary,
      and respiratory tracts. Mesenchyme surrounding the notochord and adjacent to the
      ectodermal epithelia of the oral cavity and developing teeth also expresses FREAC
      1. The pattern of FREAC-1 expression, with highest levels in the mesenchyme next
      to the epithelium and gradually diminishing as the distance from the epithelium
      increases, suggests that FREAC-1 expression is a response to epithelial paracrine
      signaling and that FREAC-1 may play a role in epitheliomesenchymal interactions.

PMID- 9769172
TI  - Normal reproductive and macrophage function in Pem homeobox gene-deficient mice.
AB  - Interaction between germ cells and the supporting somatic cells guides many of
      the differentiative processes of gametogenesis. The expression pattern of the Pem
      homeobox gene suggests that it may mediate specific inductive events in murine
      reproductive tissues. During gestation, Pem is expressed in migrating and early
      postmigratory primordial germ cells, as well as in all embryo-derived
      extraembryonic membranes. Pem expression ceases in the germline after Embryonic
      Day 14 in both sexes and then reappears postnatally in the supporting cells of
      the gonad. In mature mice, Pem is produced by testicular Sertoli cells during
      stages VI-VIII of spermatogenesis and transiently by ovarian granulosa cells
      lining periovulatory follicles. Despite this tightly regulated reproductive
      expression pattern, mice with a targeted mutation in Pem have normal fecundity,
      with no detectable alteration in extraembryonic testicular or ovarian development
      or function. We also show that Pem is expressed throughout embryonic and adult
      development in a subset of a tissue-specific class of macrophages, Kupffer cells,
      as well as in a localized fraction of cells in macrophage cell lines. Although
      the number of Pem-positive Kupffer cells increases in mice treated with
      lipopolysaccharide, loss of Pem does not detectably interfere with the cells'
      ability to induce iNOS expression, demonstrating this Kupffer cell function does
      not require Pem. No differences were observed between Pem-knockout mice in 129,
      C57BL6/J, or mixed genetic backgrounds. Together, these data show that Pem is
      dispensable for embryonic and postnatal development, gonadal function, and
      Kupffer cell activation, perhaps due to compensatory expression of a similar
      homeobox gene.

PMID- 9769173
TI  - Analysis of epithelial-mesenchymal interactions in the initial morphogenesis of
      the mammalian tooth.
AB  - Epithelial-mesenchymal interactions govern the development of epidermal organs
      such as teeth. During the early stages of tooth development, a local ectodermal
      thickening which expresses several signaling molecules appears. It is believed
      that these in turn signal to the underlying mesenchyme triggering mesenchymal
      condensation and tooth development. For example, epithelially expressed Bmp4
      induces Msx1 and Lef1 as well as itself in the underlying mesenchyme. In this
      paper we have investigated the role of four epithelial signaling molecules, Bmp2,
      Shh, Wnt10a, and Wnt10b, in the early inductive cascades that govern tooth
      development. We show that all four genes are specifically expressed in the
      epithelium between E11.0 and E12.0 when tooth morphogenesis is first apparent.
      Although Shh, Bmp2, and Wnt10b have similar, if not identical, expression
      patterns, each signal has a distinct molecular action on the jaw mesenchyme.
      Whereas Shh and Wnt10b can induce general Hedgehog and Wnt targets, Ptc and Gli
      for Shh and Lef1 for Wnt10b, only Bmp2 is able to induce tooth-specific
      expression of Msx1. Thus, there are distinct targets for all three pathways.
      Interestingly, both Bmp and Wnt signaling activate Lef1, making it a candidate
      for integrating the two distinct signaling pathways.

PMID- 9769174
TI  - The classical mouse mutant postaxial hemimelia results from a mutation in the Wnt
      7a gene.
AB  - The study of spontaneous mutations has aided the understanding of developmental
      processes. A large collection of spontaneous or "classical" mouse mutations has
      been accumulated over many decades. One of the mutations causes the postaxial
      hemimelia (px) phenotype, which consists of limb patterning defects accompanied
      by Mullerian duct-associated sterility in both sexes. We were intrigued that both
      the limb and the Mullerian duct px phenotypes are similar to those caused by
      mutations in the gene encoding the Wnt 7a signaling molecule. In this paper, we
      investigate the nature of the px mutation. Morphological analysis and breeding
      experiments demonstrate that the px phenotype indeed results from a mutation in
      the Wnt 7a gene. Molecular analysis demonstrates that px results from a 515-bp
      deletion in the Wnt 7a gene. This generates an abnormal splicing event, which
      ultimately produces a truncated Wnt 7a protein of half the normal size. Thus, the
      px mutation is predicted to be a likely null allele of the Wnt 7a gene. Our
      results provide another interesting example of a classical mutation that disrupts
      an important patterning gene in development.

PMID- 9769175
TI  - Chondroitin sulfates modulate axon guidance in embryonic Xenopus brain.
AB  - Chondroitin sulfate proteoglycans display both inhibitory and stimulatory effects
      on cell adhesion and neurite outgrowth in vitro. The functional activity of these
      proteoglycans appears to be context specific and dependent on the presence of
      different chondroitin sulfate-binding molecules. Little is known about the role
      of chondroitin sulfate proteoglycans in the growth and guidance of axons in vivo.
      To address this question, we examined the effects of exogenous soluble
      chondroitin sulfates on the growth and guidance of axons arising from a
      subpopulation of neurons in the vertebrate brain which express NOC-2, a novel
      glycoform of the neural cell adhesion molecule N-CAM. Intact brains of stage 28
      Xenopus embryos were unilaterally exposed to medium containing soluble exogenous
      chondroitin sulfates. When exposed to chondroitin sulfate, NOC-2(+) axons within
      the tract of the postoptic commissure failed to follow their normal trajectory
      across the ventral midline via the ventral commissure in the midbrain. Instead,
      these axons either stalled or grew into the dorsal midbrain or continued growing
      longitudinally within the ventral longitudinal tract. These findings suggest that
      chondroitin sulfate proteoglycans indirectly modulate the growth and guidance of
      a subpopulation of forebrain axons by regulating either matrix-bound or cell
      surface cues at specific choice points within the developing vertebrate brain.

PMID- 9769176
TI  - Glycosylphosphatidylinositol-anchored cell surface proteins regulate position
      specific cell affinity in the limb bud.
AB  - Although regional differences in mesenchymal cell affinity in the limb bud
      represent positional identity, the molecular basis for cell affinity is poorly
      understood. We found that treatment of the cell surface with bacterial
      phosphatidylinositol-specific phospholipase C (PI-PLC) could change cell affinity
      in culture. When PI-PLC was added to the culture medium, segregation of the
      progress zone (PZ) cells from different stage limb buds was inhibited. Similarly,
      sorting out of the cells from different positions along the proximodistal (PD)
      axis of the same stage limb buds was disturbed. Since PI-PLC can remove
      glycosylphosphatidylinositol (GPI)-anchored membrane bound proteins from the cell
      surface, the GPI-anchored cell surface proteins may be involved in sorting out.
      To define the GPI-anchored molecules that determine the segregation of limb
      mesenchymal cells, we examined the effect of neutralizing antibody on the EphA4
      receptor that binds to GPI-anchored cell surface ligands, called ephrin-A.
      Sorting out of the PZ cells at different stages could be inhibited by the
      neutralizing antibody to EphA4. These results suggest that EphA4 and its GPI
      anchored ligands are, at least in part, involved in sorting out of limb
      mesenchymal cells with different proximal-distal positional values, and that GPI
      anchored cell surface proteins play important roles in determining cell affinity
      in the limb bud.

PMID- 9769177
TI  - Experimental induction of BMP-4 expression leads to apoptosis in the paraxial and
      lateral plate mesoderm.
AB  - In the avian embryo, epithelialization of the segmental plate and formation of an
      epithelial dermomyotome depend on signals from the neural tube and the ectoderm
      overlying the paraxial mesoderm. In this study, we report that ectoderm removal
      in combination with barrier insertion between the axial organs and the segmental
      plate leads to an induction of BMP-4 expression in the paraxial mesoderm. In the
      lateral plate, ectoderm removal alone leads to an increase of BMP-4 expression.
      Application of BMP-4 protein results in a lack of epithelialization of the
      paraxial mesoderm. In order to investigate whether the loss of epithelial
      structures after these manipulations can be attributed to a change in cell fate,
      a change in cell proliferation, or the induction of apoptosis, the paraxial
      mesoderm was tested for expression of Msx-2, BMP-2, BMP-4, and BMP-7. Moreover,
      BrdU and TUNEL staining were carried out. The inhibition of epithelialization
      after ectoderm removal alone and after segregation of the axial organs is
      accompanied neither by an increase in apoptosis nor by a reduction of the
      proliferation rate in the paraxial mesoderm. On the other hand, an ectopic BMP-4
      expression in the paraxial mesoderm after ectoderm removal in combination with
      barrier insertion coincides with the occurrence of apoptotic cells and reduction
      of proliferation rate in this tissue. Increase of apoptosis and decrease in cell
      proliferation are observed in the paraxial and lateral plate mesoderm also after
      application of BMP-4 protein.

PMID- 9769178
TI  - Regulation of the trunk-tail patterning in the ascidian embryo: a possible
      interaction of cascades between lithium/beta-catenin and localized maternal
      factor pem.
AB  - Embryonic cell specification and pattern formation in the ascidian embryo are
      controlled by prelocalized egg cytoplasmic determinants. In previous studies, we
      showed that overexpression of a maternal gene, posterior end mark (pem), whose
      transcript localizes to posterior-vegetal cytoplasm of the fertilized egg, causes
      a loss of the anterior and dorsal structures of the larva (Yoshida et al.,
      Development 122, 2005-2012, 1996). In the present study, first we observed that
      lithium treatment resulted in reduction of the larval tail. Lineage tracing
      analyses revealed that descendants of the A4.1 blastomere of the 8-cell-stage
      embryo (which forms the greater part of notochord and nerve cord) were missing
      from the tail region, that they were translocated anteriorly into the trunk
      region, and that the fate of the A4.1-line notochord cells had changed to
      endoderm. These results suggest that lithium treatment affects the trunk-tail
      patterning during embryogenesis by changing the cell fate of specific cell
      lineages. Second, we showed that lithium treatment could rescue the anterior and
      dorsal structures in pem-overexpressed larvae. This result suggests that pem
      plays a role in the patterning of the ascidian embryo via a signaling cascade
      that is affected by lithium. Third, we isolated an ascidian beta-catenin gene and
      found that overexpression of beta-catenin in the A4.1 blastomere had effects very
      similar to lithium treatment, such as reduction of the tail and anterior
      translocation of A4.1 descendants. These results suggest that the target of
      lithium is, at least in part, the Wnt-signaling cascade and that pem may also
      function via this cascade.

PMID- 9769179
TI  - Temporal restriction of MyoD induction and autocatalysis during Xenopus mesoderm
      formation.
AB  - In Xenopus, the activation of the myogenic determination factors MyoD and Myf-5
      in the muscle-forming region of the embryo occurs in response to mesoderm
      inducing factors (MIFs). Different members of the FGF, TGF-beta, and Wnt protein
      families have been implicated in this process, but how MIFs induce the myogenic
      regulators is not known. For MyoD, the induction process may serve to locally
      stabilize a transient burst of ubiquitous transcription at the midblastula
      transition, possibly by triggering MyoD's autocatalytic loop. Here we have sought
      to distinguish separate activating functions during MyoD induction by analyzing
      when MyoD responds to different MIF signaling or to MyoD autoactivation. We show
      that MyoD induction depends on the developmental age of the induced cells, rather
      than on the type or time point of inducer application. At the permissive time, de
      novo MyoD induction by Activin requires less than 90 min, arguing for an
      immediate response, rather than a series of inductive events. MyoD autoactivation
      is direct, but subject to the same temporal restriction as MyoD induction by MIF
      signaling. Further evidence implicating MyoD autocatalysis as an essential
      component of the induction process comes from the observation that both
      autocatalysis and induction of MyoD are selectively repressed by a dominant
      negative MyoD mutant. In summary, our observations let us conclude that MyoD's
      expression domain in the embryo results from an interplay of timed changes in
      cellular competence, pleiotropic signaling pathways, and autocatalysis.

PMID- 9769180
TI  - Activin A and follistatin influence expression of somatostatin in the ciliary
      ganglion in vivo.
AB  - An important developmental question concerns whether neurotransmitter phenotype
      is an inherent property of neurons or is influenced by target tissues. This issue
      can be addressed in the avian ciliary ganglion (CG) which contains two
      cholinergic populations, ciliary and choroid neurons, that differentially express
      the peptide cotransmitter, somatostatin. The present study tests the hypothesis
      that differences in the level of expression of activin A and its endogenous
      inhibitor follistatin in CG neuron target tissues are responsible for selective
      expression of somatostatin in choroid neurons. Intraocular injection of activin A
      or follistatin (300 ng injected at E10/E11) in cultured embryos resulted in a 39%
      increase or a 23% decrease, respectively, in somatostatin-positive neurons
      relative to controls. Chorioallantoic membrane application of follistatin (1
      microgram daily from E7 to E13) reduced somatostatin positive neurons by 54%.
      Neuron number, size, and target tissue morphology were unaffected by these
      treatments. Together with our previous studies, these data suggest that activin A
      and follistatin are target-derived molecules that regulate neuropeptide phenotype
      in the ciliary ganglion.

PMID- 9769181
TI  - Tissues exhibiting inhibitory [correction of inhibiory] and repulsive activities
      during the initial stages of neurite outgrowth from the dorsal root ganglion in
      the chick embryo.
AB  - To elucidate the mechanisms underlying the projection of dorsal root ganglion
      (DRG) axons into the dorsal root entry zone in the dorsolateral region of the
      spinal cord, we examined tissue interactions which affect neurite outgrowth from
      DRG. We cultured explants or dissociated cells of DRG from embryonic day 4 (E4)
      chick embryos in combination with E3 spinal cord, notochord, and dermomyotome in
      three-dimensional collagen gels. The ventral spinal cord, notochord, and
      dermomyotome, which are located close to the initial projection pathway of DRG
      but do not receive direct innervation, strongly inhibited DRG neurite outgrowth
      and repelled DRG neurites. These inhibitory/repulsive cues appear diffusible in
      nature, because this activity was observed in the absence of direct contacts
      between tissue explants and DRG neurites. Furthermore, in heterochronic cultures,
      E9 DRG lost its responsiveness to inhibitory/repulsive factors from E3 ventral
      spinal cord, while retaining responsiveness to E3 notochord and dermomyotome,
      suggesting that the E3 ventral spinal cord may secrete a different
      inhibitory/repulsive signal than notochord and dermomyotome. Putative
      inhibitory/repulsive signals secreted from tissues along the axonal pathway may
      serve to guide growing DRG axons to the dorsal root entry zone.

PMID- 9769182
TI  - Volume 199, number 1 (1998), in article no. DB988905, "A constitutive mutation of
      ALK5 disrupts cardiac looping and morphogenesis in Mice," by min-Ji charng, peter
      A. Frenkel, qing lin, miho yamada, robert J. Schwartz, eric N. Olson, paul
      overbeek, and michael D. Schneider, pages 72-79: 

PMID- 9769183
TI  - Calibration of Comprehension: Research and Implications for Education and
      Instruction.
AB  - The ability to accurately evaluate one's understanding of text information is
      critical for optimum learning to take place. One widely used paradigm for
      examining the accuracy of individuals' self-assessed comprehension has been
      termed calibration of comprehension. In this paradigm, students read a passage
      and are asked to make predictions about their future performance on a
      comprehension test. Calibration of comprehension is the relation between
      students' confidence and performance or between predicted and actual performance.
      In the present paper we review research on calibration of comprehension,
      examining a number of variables that have been found to influence calibration
      ability. In the first three sections of our paper we focus on the effects of
      individual, task, and text variables on students' calibration of comprehension.
      In the final section, we discuss implications of research on calibration for
      education and instruction. Copyright 1998 Academic Press.

PMID- 9769184
TI  - Modeling the Mediating Role of Volition in the Learning Process.
AB  - According to action-control theory, volition plays a mediating role between the
      intention to learn (motivation) and goal-directed behavior (the use of learning
      strategies). Although extensive theoretical work has been done to document this
      flow of events, more empirical studies have been needed to identify the specific
      means by which volitional control protects the intention to learn and maintains
      the attempts to learn; our intention here was to address this gap in the
      literature. Using data from a sample of 487 college students in two different
      domains, we found that the positive effects of intrinsic goal orientation and
      self-efficacy on cognitive engagement were augmented by volitional control. We
      also found that the effects of volition differed by domain as well as by the type
      of learning strategy being considered. These results suggest that volitional
      control merits greater attention from those doing research in self-regulated
      learning. Copyright 1998 Academic Press.

PMID- 9769185
TI  - Very Long-Term Memory for Information Taught in School.
AB  - Students who completed a Child Development course (N = 1168) from 3 to 16 years
      prior to retention testing were tested for recognition and recall of facts and
      application of mental skills. Students who subsequently served as course tutors
      were also tested for retention. Fact retention was superior to application
      retention and retention for both question types declined rapidly from year 3 to
      year 7 after which it stabilized. Recognition items were superior to recall items
      for high achieving students only. Tutors retained more than non-tutors for eight
      years after which there were no differences. Copyright 1998 Academic Press.

PMID- 9769186
TI  - A Comparison of Self-Explanation and Elaborative Interrogation.
AB  - The purpose of the present study was to examine the effectiveness of two learning
      strategies, self-explanation and elaborative interrogation, for the retention of
      scientific facts. University students (N = 55) were asked to learn facts about
      the cardiovascular system using one of three approaches. Self-explanation
      participants were required to explain what the facts meant to them and how they
      related to their prior knowledge. Elaborative interrogation participants answered
      "why" the facts made sense. Finally, the control group simply repeated the facts
      aloud. Self-explanation participants significantly outperformed elaborative
      interrogation and repetition control participants on measures of cued recall and
      recognition. Elaborative interrogation was no more effective than repetition.
      Results were discussed in terms of the practicality and flexibility of each
      approach. Copyright 1998 Academic Press.

PMID- 9769208
TI  - Conformational flexibility in a highly mobile protein loop of foot-and-mouth
      disease virus: distinct structural requirements for integrin and antibody
      binding.
AB  - The G-H loop of foot-and-mouth disease virus VP1 protein is a highly mobile
      peptide, that extends from the capsid surface and that in native virions is
      invisible by X-ray crystallography. In serotype C, this segment contains a
      hypervariable region with several continuous, overlapping, B-cell epitopes that
      embrace the conserved Arg-Gly-Asp (RGD) cell attachment motif. The solvent
      exposed positioning of this peptide by selective insertion into different
      structural frameworks of E. coli beta-galactosidase, generates a spectrum of
      antigenic variants which react distinctively with a panel of anti-VP1 monoclonal
      antibodies and exhibit different efficiencies as cell ligands. The cell
      attachment efficiency is much less restricted by the different positioning of the
      viral segment at the insertion sites. A molecular model of an inserted stretch
      reveals a highest flexibility of the RGD tripeptide segment compared with the
      flanking sequences, that could allow a proper accommodation to integrin receptors
      even in poorly antigenic conformations. The non-converging structural
      requirements for RGD-mediated integrin binding and antibody recognition, explains
      the dynamism of the generation of neutralisation-resistant antigenic variants in
      the viral quasi-species, arising from a conformational space of integrin-binding
      competent peptides. This might be of special relevance for foot-and-moth disease
      virus evolution, since unlike in other picornaviruses, the cell binding motif and
      the major neutralising B-cell epitopes overlap in a solvent-exposed peptide
      accessible to the host immune system, in a virion lacking canyons and similar
      hiding structures.

PMID- 9769209
TI  - NasR, a novel RNA-binding protein, mediates nitrate-responsive transcription
      antitermination of the Klebsiella oxytoca M5al nasF operon leader in vitro.
AB  - In Klebsiella oxytoca (pneumoniae), enzymes required for nitrate assimilation are
      encoded by the nasFEDCBA operon. Previous genetic studies led to the conclusion
      that nitrate and nitrite induction of nasF operon expression is determined by a
      transcriptional antitermination mechanism. In the presence of nitrate or nitrite,
      the nasR gene product is hypothesized to inhibit transcription termination at the
      factor-independent terminator site located in the nasF operon leader region. To
      test this model in vitro, we first purified NasR as both a maltose binding
      protein fusion form (MBP-NasR) and a His6-tagged form (His6-NasR). Templates for
      in vitro transcription contained the nasF operon leader region, with a
      substitution of the sigma70-dependent tac promoter for the native sigmaN
      dependent promoter. We found that in vitro transcription of the leader template
      terminated at the terminator site, and that MBP-NasR and His6-NasR proteins both
      caused transcription readthrough of this site in response to nitrate or nitrite.
      Half-maximal antitermination required nitrate or nitrite at moderate (1 to 10
      microM) concentrations, and several other anions tested, including chlorate, were
      without effect. Previous in vivo analysis of leader deletions identified regions
      required for both negative regulation (the terminator) and for positive
      regulation. Results from in vitro transcription of these deletion templates
      correlated fully with the in vivo analysis. Finally, electrophoresis mobility
      shift analysis revealed that His6-NasR bound specifically to nasF leader RNA.
      This binding was independent of nitrate in vitro. These results strongly support
      the conclusions drawn from previous in vivo analysis, and establish that NasR
      mediates ligand-responsive transcription antitermination through interaction with
      nasF leader RNA.

PMID- 9769210
TI  - Stopped-flow kinetic analysis of the interaction of Escherichia coli RNA
      polymerase with the bacteriophage T7 A1 promoter.
AB  - We have conducted a detailed kinetic and thermodynamic analysis of open complex
      formation between Escherichia coli RNA polymerase and the A1 promoter from
      bacteriophage T7 by monitoring alterations in the intrinsic protein fluorescence
      of RNA polymerase in stopped-flow kinetic studies. The stopped-flow kinetic data
      are consistent with a minimal model involving four steps for the formation of the
      open complex. Arrhenius plots for both the association and dissociation reactions
      for the equilibrium binding step leading to the formation of the closed complex
      were linear. With a positive van't Hoff enthalpy (DeltaHobs=18(+/-3) kcal mol-1)
      and a positive entropy (DeltaSobs=94(+/-15) e.u.) change for the equilibrium
      binding process, formation of the closed complex is entropy driven. The value of
      the apparent association rate constant for this binding step was approximately
      three orders of magnitude less than that expected for facilitated binding. Thus,
      a minimum of two steps is required to describe the formation of the closed
      complex. A fast facilitated binding step appears to be followed by a
      conformational change in RNA polymerase which leads to the formation of the
      closed complex. A non-linear Arrhenius plot obtained for the isomerization step
      in the conversion of the closed complex to an open one indicates that there are
      at least two steps in the conversion of the closed complex to an open one. We
      have assigned the apparent activation energy of 9.1(+/-1.9) kcal mol-1 to the
      step involving a conformational change in the protein and nucleation of strand
      separation and the apparent activation energy of 46(+/-12) kcal mol-1 to the step
      involving strand separation. At 37 degreesC, the value of the macroscopic
      isomerization rate constant (0.26(+/-0.02) s-1) in the conversion of the closed
      complex to an open one was an order of magnitude greater than the value reported
      in abortive initiation assays. This suggests that open complex formation is not
      the rate-determining step in the initiation of transcription in the case of the
      A1 promoter. To gain greater insight into the mechanism of initiation at the A1
      promoter, we investigated the process of abortive product formation (pppApU)
      under conditions of non-saturating concentrations of the initiating nucleotide. A
      comparison of the lag times in the approach to the steady-state rate of abortive
      product formation when the reaction was initiated by the addition of UTP, ATP,
      the enzyme and the A1 promoter, respectively, indicates that the initiating
      nucleotide plays a key regulatory role in the initiation of transcription in the
      case of the A1 promoter.

PMID- 9769211
TI  - Structure and expression of elongation factor Tu from Bacillus
      stearothermophilus.
AB  - The tuf gene coding for elongation factor Tu (EF-Tu) of Bacillus
      stearothermophilus was cloned and sequenced. This gene maps in the same context
      as the tufA gene of Escherichia coli str operon. Northern-blot analysis and
      primer extension experiments revealed that the transcription of the tuf gene is
      driven from two promoter regions. One of these is responsible for producing a 4.9
      kb transcript containing all the genes of B. stearothermophilus str operon and
      the other, identified adjacent to the stop codon of the fus gene and designated
      tufp, for producing a 1.3-kb transcript of the tuf gene only. In contrast to the
      situation in E. coli, the ratio between the transcription products was found to
      be about 10:1 in favour of the tuf gene transcript. This high transcription
      activity from the tufp promoter might be accounted for by the presence of an
      extremely A+T-rich block consisting of 29 nucleotides which immediately precedes
      the consensus -35 region of the promoter. A very similar tuf gene transcription
      strategy and the same tufp promoter organization with the identical A/T block
      were found in Bacillus subtilis. The tuf gene specifies a protein of 395 amino
      acid residues with a molecular mass of 43,290 Da, including the N-terminal
      methionine. A computer-generated three-dimensional homology model shows that all
      the structural elements essential for binding guanine nucleotides and aminoacyl
      tRNA are conserved. The presence of serine at position 376 and a low affinity for
      kirromycin determined by zone-interference gel electrophoresis (Kd approximately
      8 microM) and by polyacrylamide gel electrophoresis under non-denaturing
      conditions are in agreement with the reported resistance of this EF-Tu to the
      antibiotic. The replacement of the highly conserved Leu211 by Met was identified
      as a possible cause of pulvomycin resistance.

PMID- 9769212
TI  - A supraspliceosome model for large nuclear ribonucleoprotein particles based on
      mass determinations by scanning transmission electron microscopy.
AB  - Pre-mRNA splicing is an important regulatory step in the expression of most
      eukaryotic genes. In vitro studies have shown splicing to occur within 50-60 S
      multi-component ribonucleoprotein (RNP) complexes termed spliceosomes. Studies of
      mammalian cell nuclei have revealed larger complexes that sediment at 200 S in
      sucrose gradients, termed large nuclear RNP (lnRNP) particles. These particles
      contain all factors required for pre-mRNA splicing, including the spliceosomal U
      snRNPs and protein splicing factors. Electron microscopy has shown them to
      consist of four apparently similar substructures. In this study, mass
      measurements by scanning transmission electron microscopy of freeze-dried
      mammalian lnRNP preparations, both confirm the similarity between the lnRNP
      particles and reveal the mass uniformity of their subunits. Thus, the tetrameric
      lnRNP particle has a mass of 21.1(+/-1.6) MDa, while each repeating subunit has a
      mass of 4.8(+/-0.5) MDa, which is close to the estimated mass of the fully
      assembled 60 S spliceosome. The 1.9 MDa discrepancy between the lnRNP particle's
      mass and the cumulative masses of its four subunits may be attributed to an
      additional domain frequently observed in the micrographs. Notably, strands and
      loops of RNA were often seen emanating from lnRNP particles positively stained
      with uranyl formate. Our results support the idea that the nuclear splicing
      machine is a supraspliceosome complex. For clarity, we define spliceosomes devoid
      of pre-mRNA as spliceosome cores, and propose that the supraspliceosome is
      constructed from one pre-mRNA, four spliceosome cores, each composed mainly of U
      snRNPs, and additional proteins. In this way a frame is provided to juxtapose
      exons about to be spliced.

PMID- 9769213
TI  - Reproducing the natural evolution of protein structural features with the
      selectively infective phage (SIP) technology. The kink in the first strand of
      antibody kappa domains.
AB  - The beta-sandwich structure of immunoglobulin variable domains is characterized
      by a typical kink in the first strand, which allows the first part of the strand
      to hydrogen bond to the outer beta-sheet (away from the VH-VL interface) and the
      second part to the inner beta-sheet. This kink differs in length and sequence
      between the Vkappa, Vlambda and VH domains and yet is involved in several almost
      perfectly conserved interactions with framework residues. We have used the
      selectively infective phage (SIP) system to select the optimal kink region from
      several defined libraries, using an anti-hemagglutinin single-chain Fv (scFv)
      fragment as a model system. Both for the kink with the Vkappa domain length and
      that with the Vlambda length, a sequence distribution was selected that coincides
      remarkably well with the sequence distribution of natural antibodies. The
      selected scFv fragments were purified and characterized, and thermodynamic
      stability was found to be the prime factor responsible for selection. These data
      show that the SIP technology can be used for optimizing protein structural
      features by evolutionary approaches.

PMID- 9769214
TI  - Involvement of two novel chaperones in the assembly of mitochondrial
      NADH:Ubiquinone oxidoreductase (complex I).
AB  - The respiratory complex I of mitochondria consists of some 40 different subunits
      which form an L-shaped structure. Perpendicular to a hydrophobic arm embedded in
      the inner mitochondrial membrane a peripheral arm protrudes into the matrix.
      Assembly of the complex as studied in the fungus Neurospora crassa involves the
      formation of discrete intermediates. The matrix arm and the membrane arm are
      formed independently of each other and are joined in the course of assembly. The
      membrane arm itself is formed by association of two assembly intermediates, a
      smaller of 200 kDa and a larger of 350 kDa. The latter is associated with two
      extra proteins of 84 and 30 kDa which are not constituent parts of mature complex
      I. Their primary structures show no similarity to known proteins. Mutants
      generated by disrupting the genes of either of the two proteins accumulate the
      matrix arm of complex I and the small membrane arm assembly intermediate, but are
      incapable of forming the large intermediate. In the wild-type, the extra proteins
      exclusively associate with the large membrane arm assembly intermediate. Pulse
      chase labelling experiments showed that the two proteins are repeatedly involved
      in many assembly cycles of the intermediate. These results indicate that the two
      proteins are novel chaperones specific for complex I membrane arm assembly.

PMID- 9769215
TI  - Structure of the complex between the HIV-1 nucleocapsid protein NCp7 and the
      single-stranded pentanucleotide d(ACGCC).
AB  - The nucleocapsid protein NCp7 of HIV-1 Mal contains two successive Zn knuckles of
      the CX2CX4HX4C type and plays a major role in virion morphogenesis, genomic RNA
      packaging and viral infectivity, mainly through single-stranded nucleic acid
      binding. We report here the study by 1H 2D NMR of the complex formed between the
      (12-53)NCp7, encompassing the two Zn knuckles, and d(ACGCC), a deoxynucleotide
      sequence analog corresponding to the shortest NCp7 binding site. Ten structures
      of the (12-53)NCp7/d(ACGCC) complex have been obtained from 607 NOE-derived
      distance constraints, 28 of which are intermolecular, and from molecular dynamics
      studies. The oligonucleotide is almost perpendicular to the sequence linking the
      two Zn knuckles. The Trp37 indole ring is inserted between the C2 and G3 bases
      and stacked on the latter. The complex is stabilized by hydrophobic interactions
      and hydrogen bonds, and accounts for the observed loss of virus infectivity
      induced by mutations in the Zn knuckle domain. Thus, the interaction between
      d(ACGCC) and the inactive mutant Cys23 (12-53)NCp7 was found by NMR to be
      completely different from that observed with the wild-type peptide. A mechanism
      of action for NCp7 in virus morphogenesis and replication is proposed from these
      results, which could facilitate the design of possible antiviral agents acting by
      a new mechanism.

PMID- 9769216
TI  - X-ray structures and analysis of 11 cyclosporin derivatives complexed with
      cyclophilin A.
AB  - Eight new X-ray structures of different cyclophilin A/cyclosporin-derivative
      complexes are presented. These structures, combined with the existing three
      published cyclosporin complexes, provide a useful structural database for the
      analysis of protein-ligand interactions. The effect of small chemical differences
      on protein-ligand hydrogen-bonding, van der Waals interactions and water
      structure is presented.

PMID- 9769217
TI  - Conformational differences of an immunosuppressant peptolide in a single crystal
      and in a crystal complex with human cyclophilin A.
AB  - The crystal structure of (Thr2, Leu5, d-Hiv8, Leu10)-cyclosporin (cyclic
      peptolide SDZ 214-103) has been determined as the unbound crystal form and as a
      complex with human cyclophilin A. This pair of structures provides an example of
      a significant difference in conformation between free and bound ligand in
      crystals. The conformation of the unbound form is unlike that of both free and
      bound conformations of cyclosporin A (with the amide bond between residues 3 and
      4 in the cis conformation), while the bound conformation is similar to that of
      CsA bound to cyclophilin. The cyclophilin-bound conformations of both ligands are
      similar, though this involves a significantly different waterellipsisligand
      hydrogen-bonding structure, which compensates for the chemical differences
      between the two ligands.

PMID- 9769218
TI  - A novel three-dimensional crystal of bacteriorhodopsin obtained by successive
      fusion of the vesicular assemblies.
AB  - When the two-dimensional crystal of bacteriorhodopsin (bR), purple membrane, is
      incubated at high temperature (32 degreesC) with a small amount of the neutral
      detergent octylthioglucoside in the presence of the precipitant ammonium sulfate,
      a large fraction of the membrane fragments is converted into spherical vesicles
      with a diameter of 50 nm, which are able to assemble into optically isotropic
      hexagonal crystals when the precipitant concentration is increased. The
      vesicularization of purple membrane takes place under such a condition that the
      miscibility of the detergent to the aqueous phase becomes very low, and we
      suggest that it is initiated by insertion of the detergent molecules into the
      membrane. At low temperature, the transformation into the vesicular structure is
      inhibited and no large crystal is produced directly from
      membrane/detergent/precipitant mixtures. When a suspension of the spherical
      vesicles produced at the high temperature is cooled and concentrated below 15
      degreesC, however, a birefringent hexagonal crystal is produced that diffracts X
      rays beyond 2.5 A resolution. This new crystal belongs to the space group P622
      with unit cell dimensions of a=b=104.7 A and c=114.1 A, and it is shown to be
      made up of stacked planar membranes, in each of which the bR trimers are arranged
      on a honeycomb lattice and the space among the proteins is filled with the
      detergent molecules and native lipids. These stacked membranes are suggested to
      be produced by successive fusion of the spherical vesicles. This implies that the
      crystallization is achieved without any step for complete solubilization of the
      protein. The present result offers a unique crystallization method that may be
      applicable to such membrane proteins that are liable to denature in the presence
      of an excess amount of detergent.

PMID- 9769219
TI  - The structural stability of the HIV-1 protease.
AB  - The most common strategy in the development of HIV-1 protease inhibitors has been
      the design of high affinity transition state analogs that effectively compete
      with natural substrates for the active site. A second approach has been the
      development of compounds that inactivate the protease by destabilizing its
      quaternary or tertiary structure. A successful optimization of these strategies
      requires an accurate knowledge of the energetics of structural stabilization and
      binding, and the identification of those regions in the protease molecule that
      are critical to stability and function. Here the energetics of stabilization of
      the HIV-1 protease has been measured for the first time by high sensitivity
      differential scanning calorimetry. These studies have permitted the evaluation of
      the different components of the Gibbs energy of stabilization (the enthalpy,
      entropy and heat capacity changes). The stability of the protease is pH-dependent
      and due to its dimeric nature is also concentration-dependent. At pH 3.4 the
      Gibbs energy of stabilization is close to 10 kcal/mol at 25 degreesC, consistent
      with a dissociation constant of 5x10(-8) M. The stability of the protease
      increases at higher pH values. At pH 5, the Gibbs energy of stabilization is 14.5
      kcal/mol at 25 degreesC, consistent with a dissociation constant of 2.3x10(-11)
      M. The pH dependence of the Gibbs energy of stabilization indicates that between
      pH 3.4 and pH 5 an average of 3-4 ionizable groups per dimer become protonated
      upon unfolding. A structure-based thermodynamic analysis of the protease molecule
      indicates that most of the Gibbs energy of stabilization is provided by the
      dimerization interface and that the isolated subunits are intrinsically unstable.
      The Gibbs energy, however, is not uniformly distributed along the dimerization
      interface. The dimer interface is characterized by the presence of clusters of
      residues (hot spots) that contribute significantly and other regions that
      contribute very little to subunit association. At the dimerization interface,
      residues located at the carboxy and amino termini contribute close to 75% of the
      total Gibbs energy (Cys95, Thr96, Leu97, Asn98 and Phe99 and Pro1, Ile3, Leu5).
      Residues Thr26, Gly27 and Asp29 located at the base of the active site are also
      important, and to a lesser extent Gly49, Ile50, Gly51 located at the tip of the
      flap region. The structure-based thermodynamic analysis also predicts the
      existence of regions of the protease with only marginal stability and a high
      propensity to undergo independent local unfolding. In particular, the flap region
      occupies a very shallow energy minimum and its conformation can easily be
      affected by relatively small perturbations. This property of the protease can be
      related to the ability of some mutations to elicit resistance towards certain
      inhibitors.

PMID- 9769220
TI  - Principles governing amino acid composition of integral membrane proteins:
      application to topology prediction.
AB  - A new method is suggested here for topology prediction of helical transmembrane
      proteins. The method is based on the hypothesis that the localizations of the
      transmembrane segments and the topology are determined by the difference in the
      amino acid distributions in various structural parts of these proteins rather
      than by specific amino acid compositions of these parts. A hidden Markov model
      with special architecture was developed to search transmembrane topology
      corresponding to the maximum likelihood among all the possible topologies of a
      given protein. The prediction accuracy was tested on 158 proteins and was found
      to be higher than that found using prediction methods already available. The
      method successfully predicted all the transmembrane segments in 143 proteins out
      of the 158, and for 135 of these proteins both the membrane spanning regions and
      the topologies were predicted correctly. The observed level of accuracy is a
      strong argument in favor of our hypothesis.

PMID- 9769221
TI  - Protein structure prediction by threading. Why it works and why it does not.
AB  - We developed a novel Monte Carlo threading algorithm which allows gaps and
      insertions both in the template structure and threaded sequence. The algorithm is
      able to find the optimal sequence-structure alignment and sample suboptimal
      alignments. Using our algorithm we performed sequence-structure alignments for a
      number of examples for three protein folds (ubiquitin, immunoglobulin and globin)
      using both "ideal" set of potentials (optimized to provide the best Z-score for a
      given protein) and more realistic knowledge-based potentials. Two physically
      different scenarios emerged. If a template structure is similar to the native one
      (within 2 A RMS), then (i) the optimal threading alignment is correct and robust
      with respect to deviations of the potential from the "ideal" one; (ii) suboptimal
      alignments are very similar to the optimal one; (iii) as Monte Carlo temperature
      decreases a sharp cooperative transition to the optimal alignment is observed. In
      contrast, if the template structure is only moderately close to the native
      structure (RMS greater than 3.5 A), then (i) the optimal alignment changes
      dramatically when an "ideal" potential is substituted by the real one; (ii) the
      structures of suboptimal alignments are very different from the optimal one,
      reducing the reliability of the alignment; (iii) the transition to the apparently
      optimal alignment is non-cooperative. In the intermediate cases when the RMS
      between the template and the native conformations is in the range between 2 A and
      3.5 A, the success of threading alignment may depend on the quality of potentials
      used. These results are rationalized in terms of a threading free energy
      landscape. Possible ways to overcome the fundamental limitations of threading are
      discussed briefly.

PMID- 9769222
TI  - In this issue 

PMID- 9769223
TI  - Chromatin structure and cardiac gene expression.
AB  - Gene activation is often preceded by or accompanied by a perturbation of the
      chromatin structure. Recently, several co-factors of transcription factors have
      been identified as histone acetyltransferases. In addition, retinoblastoma
      protein and some co-factors can form a complex with histone deacetylases. These
      discoveries provide direct evidence that modification of chromatin structure is
      crucial for gene activation. However, the role of chromatin structure in cardiac
      specific expression has not yet been elucidated. The potential significance of
      chromatin structure in cardiac-specific gene expression is indicated by: (1)
      heterogeneous human SWI/SNF chromatin remodelling factors among various tissues;
      (2) several chromatin remodelling factors shown to be expressed preferentially in
      the heart; (3) the demonstration of chromatin remodelling of the cardiac beta
      myosin heavy chain gene (MyHC) during cardiac development. We therefore propose
      to study cardiac-specific chromatin remodelling activity in order to elucidate
      mechanisms controlling the reactivation of the fetal heart genetic program in the
      hypertrophic heart.

PMID- 9769224
TI  - Human myocardial tissue TNFalpha expression following acute global ischemia in
      vivo.
AB  - Although human myocardial TNFalpha levels are increased during the ischemia
      associated with chonic heart failure, it remains unknown whether an acute global
      ischemic insult further increases TNFalpha expression in human cardiac myocytes.
      To study this, biopsies of human myocardium were obtained before and after
      cardiopulmonary bypass (in vivo acute global ischemia), and myocardial TNFalpha
      levels were determined by ELISA and cytotoxicity assay (WEHI-164 clone 13 cell
      line). TNFalpha was immunolocalized by immunohistochemistry. Results indicate
      that cardiopulmonary bypass induces an increase in human myocardial TNFalpha by
      both ELISA and cytotoxicity assays. Immunolocalization revealed that prior to
      cardiopulmonary bypass TNFalpha was located predominantly in the myocardial
      interstitial cells; however, following bypass, increased TNFalpha was observed in
      the cardiocytes themselves. Locally-produced myocardial TNFalpha may be an
      important contributor to myocardial functional depression and injury following
      acute ischemia. Targeted anti-TNFalpha therapy in the treatment of cardiac
      ischemic injury may further elucidate its clinical relevance.

PMID- 9769225
TI  - A high affinity binding site for [3H]-Dofetilide on human leukocytes.
AB  - Certain Class III anti-arrhythmic agents have been shown to interact with human
      leukocytes and after antigenic and mitogenic activation. We hypothesized that a
      binding site for the Class III anti-arrhythmic agent, dofetilide, would exist on
      human leukocytes. Analysis of binding isotherms defined the presence of a single
      high affinity binding site on mononuclear cells and neutrophils: Kd 26+/-4 nm,
      Bmax 61+/-14 fmol/10( 6) cells and Kd 33+/-14 nm, Bmax 163+/-45 fmol/10(6) cells,
      respectively. Other Class III drugs inhibited [3H]-dofetilide binding at
      physiologically relevant concentrations, but the IC50 values of E4031 and
      quinidine were significantly higher for leukocytes than for cardiac myocytes.
      Interestingly, verapamil inhibited [3H]-dofetilide binding to leukocytes, but not
      to cardiac myocytes at physiologic concentrations (10 microM). Charybdotoxin and
      tetraethlyammonium inhibited [3H]-dofetilide binding to leukocytes at microM mm
      concentrations, respectively, however, apamin did not inhibit binding even at 1
      microM concentrations. These data suggest that a Ca2+-activated K+ channel, like
      K(Ca) mini (apamin-insensitive isoform), is a candidate for the leukocyte [3H]
      dofetilide binding site. To assess the functional significance of defetilide
      binding to leukocyte biology, we evaluated fMLP-stimulated superoxide production
      in the presence or absence of dofetilide. Dofetilide, at 30 nm suppressed of
      superoxide production. In conclusion, dofetilide binds to human leukocytes at
      physiologic concentrations and this binding alters leukocyte function possibly
      through interaction with a Ca2+-activated K+ channel.

PMID- 9769226
TI  - The role of glycolysis in myocardial calcium control.
AB  - Because glycolysis is thought to be important for maintenance of cellular ion
      homeostasis, the aim of the present study was to examine the role of glycolysis
      in the control of cytosolic calcium ([Ca2+]i) and cell shortening during
      conditions of increased calcium influx. Thus, [Ca2+]i and unloaded cell
      shortening were measured in fura-2/AM loaded rat ventricular myocytes. All cells
      were superfused with Tyrode's solution containing glucose and pyruvate (to
      preserve oxidative metabolism), and glycolysis was inhibited by iodoacetate (IAA,
      100 microM). Calcium influx was increased, secondary to an increase in
      intracellular sodium, by addition of veratrine (1 microgram/ml), or directly by
      either elevating [Ca2+]o from 2 to 5 mM or by exposing the cells to isoproterenol
      (1 to 100 nm). Veratrine exposure caused a time-dependent increase in both
      diastolic and systolic [Ca2+]i that resulted in cellular calcium overload and
      hypercontraction. The rate of increase in [Ca2+]i was more rapid in IAA-treated
      than in untreated myocytes, leading to a 13+/-3 v 5+/-2% increase (P<0.05) in
      diastolic [Ca2+]i after 5 min of exposure. The corresponding increases in
      systolic [Ca2+]i were 43+/-6 and 24+/-5% (P<0.05). Elevated [Ca2+]o resulted in
      increased [Ca2+]i transient amplitudes and cell shortening. These responses were
      each attenuated by inhibiting glycolysis, so that the increase was 38+/-5 v 68+/
      9% ([Ca2+]i transient amplitude, P<0.05) and 41+/-11 v 91+/-18% (cell shortening,
      P<0.05). Inhibition of glycolysis did not, however, affect the increase in
      calcium transient or cell shortening during addition of isoproterenol. We
      conclude that glycolysis plays an essential role in the maintenance of
      intracellular calcium homeostasis during severe calcium overload. Glycolysis was
      also essential for signalling the inotropic effect that accompanied elevation in
      extracellular calcium, while the changes in intracellular calcium following
      administration of isoproterenol were not influenced by glycolysis in the present
      model.

PMID- 9769227
TI  - Microtubules are needed for dispersal of alpha-myosin heavy chain mRNA in rat
      neonatal cardiac myocytes.
AB  - In some cell types, microtubules are used for transport of mRNA through the
      cytoplasm to the translation site. The number of microtubules increases during
      growth of cardiac myocytes, suggesting a functional role exists. Here, we test
      the need for microtubules to transport alpha-myosin heavy chain (alpha-MyHC) mRNA
      through the cytoplasm of neonatal cardiac myocytes. The alpha-MyHC mRNA
      concentration was assessed by non-radioactive in situ hybridization. The relative
      mRNA distributions were expressed as slopes (m=OD/micrometer), since optical
      density declined linearly from the nucleus to the cell periphery. Spontaneously
      contracting myocytes displayed a gradual decrease in alpha-MyHC mRNA away from
      the nucleus (m=-1.27+/-0.12 OD/micrometer). To test whether microtubules were
      necessary for alpha-MyHC mRNA dispersal, contraction was first arrested with the
      Ca2+-channel blocker verapamil (10 micrometer) for 18 h, which aggregated the
      mRNA perinuclearly. Contractile activity was then resumed by washing out
      verapamil and using isoproterenol (10 micrometer) in the presence or absence of a
      microtubule depolymerizing drug, colchicine (3 micrometer). Within 6 h, the alpha
      MyHC mRNA distribution in myocytes with microtubules returned to normal values
      (m=-1.11+/-0.14 OD/micrometer), while cells lacking microtubules maintained a
      perinuclear mRNA distribution (m-1.50+/-0.16 OD/micrometer; P<0.05 from control).
      Despite this perinuclear pattern of mRNA distribution, the myocytes still
      produced new myofibrils. These data indicate that microtubules are necessary for
      dispersal of alpha-MyHC mRNA outward from the nucleus. Furthermore,
      myofibrillogenesis may occur independently of mRNA localization and microtubule
      organization.

PMID- 9769228
TI  - Ischemic preconditioning and arrhythmogenesis in the rabbit heart: effects on
      epicardium versus endocardium.
AB  - The goals of this study were: (1) to determine if preconditioning protects
      against arrhythmias and contractile dysfunction, and if protection for these two
      endpoints occurs in parallel; and (2) to investigate the anti-arrhythmic action
      of preconditioning by examining its effect on electrical activity in epicardium v
      endocardium. We monitored ECGs, epicardial and endocardial monophasic action
      potentials (MAP), left-ventricular developed presssure (LVDP) and end-diastolic
      pressure (EDP) in isolated rabbit hearts. Hearts were subjected to a 30-min test
      ischemia and 45 min of reperfusion. Preconditioning cycles (PC) consisted of 1-4
      ischemic episodes (5 min each separated by 10 min of reperfusion) administered 30
      min before the test protocol. The test ischemia caused ventricular fibrillation
      (VF) in 42% of non-PC hearts. One PC totally suppressed VF (0%). The incidence of
      VF was 30% in 2 PC, 72% in 3 PC and 47% in 4 PC hearts. A large rise in EDP
      occurred in non-PC and 1 PC hearts, and this rise was prevented by 2, 3 or 4 PC.
      None of the protocols improved post-ischemic recovery of LVDP or EDP. The test
      ischemia generated a large dispersion in MAP duration between epicardium and
      endocardium (39ms), but this dispersion was markedly reduced after 1 PC (14ms).
      In conclusion, our results demonstrate that 1 PC completely protects against
      ischemia-induced VF in rabbit hearts, whereas 2 or more PC are required to
      prevent the ischemia-induced rise in EDP. Thus, preconditioning against
      arrhythmias and contractile dysfunction does not occur in parallel. Our data also
      suggest that 1 PC may exert its anti-arrhythmic effect through reduction of the
      substrate for reentrant arrhythmias during ischemia (dispersion of
      repolarization) via effects on MAP changes in endocardium.

PMID- 9769229
TI  - The role of adenosine and ATP-sensitive potassium channels in the protection
      afforded by ischemic preconditioning against the post-ischemic endothelial
      dysfunction in guinea-pig hearts.
AB  - The role of adenosine and ATP-sensitive potassium channels (KATP) in the
      mechanism of ischemic preconditioning (IPC)-induced protection against the post
      ischemic endothelial dysfunction was studied. Langendorff-perfused guinea-pig
      hearts were subjected either to 40 min of global ischemia and 40 min reperfusion
      or were preconditioned prior to the ischemia/reperfusion with three cycles of
      either 5 min ischemia/5 min reperfusion (IPC) or 5 min infusion/5 min wash-out of
      adenosine, adenosine A1 receptor agonist, N6-cyclohexyladenosine (CHA) or KATP
      opener, pinacidil. The magnitude of coronary flow reduction caused by NO-synthase
      inhibitor, Nomega-nitro-l-arginine methyl ester (l-NAME), served as an index of a
      basal endothelium-dependent vasodilator tone. Coronary overflows produced by a
      bolus of acetylcholine (ACh) and sodium nitroprusside (SNP) were used as measures
      of agonist-induced endothelium-dependent and endothelium-independent vascular
      function, respectively. The coronary flow, LVDP, ACh response and l-NAME response
      were reduced by 8, 32, 41 and 54%, respectively, while SNP response was not
      changed in the hearts subjected to ischemia/reperfusion. ACh response was fully
      restored, l-NAME response was partially restored, and SNP response was not
      affected in the hearts subjected to IPC. The post-ischemic recoveries of coronary
      flow and LVDP were not improved by IPC. The protective effect of IPC on the ACh
      response was mimicked by adenosine, CHA, and pinacidil. The protective effect of
      IPC, CHA and pinacidil was abolished by KATP antagonist, glibenclamide. The IPC
      protection was affected neither by a non-specific adenosine antagonist, 8-p
      sulfophenyltheophylline, nor by a specific adenosine A1 receptor antagonist, 8
      cyclopentyl-1, 3-dipropylxanthine (DPCPX). Our data indicate that: (1) IPC
      affords endothelial protection in the mechanism that involves activation of KATP,
      but not adenosine A1 receptors; (2) exogenous adenosine and A1 receptor agonist
      afford the protection, which might be of a potential clinical significance; (3)
      the endothelial dysfunction is not involved in the mechanism of myocardial
      stunning in guinea-pig hearts.

PMID- 9769230
TI  - Increase in the expression of biglycan mRNA expression Co-localized closely with
      that of type I collagen mRNA in the infarct zone after experimentally-induced
      myocardial infarction in rats.
AB  - Biglycan, a small dermatan sulphate proteoglycan, has been postulated to interact
      with other components of the extracellular matrix (ECM), specifically collagens.
      We hypothesized that biglycan messenger ribonucleic acid (mRNA) is increased in
      the myocardial infarct zone. Biglycan mRNA expression after acute myocardial
      infarction (AMI) in rats was determined with the use of Northern blotting and in
      situ hybridization, and its expression pattern was compared to that of type I
      collagen mRNA [alpha1(I) collagen]. The left coronary artery was ligated in male
      Sprague-Dawley rats, and the hearts were excised on days 2 and 7. The Northern
      blot analysis demonstrated that expression of biglycan mRNA in the infarct on
      days 2 and 7 were 4.0- and 6.8-fold higher, respectively, compared to the sham
      operated hearts. The in situ hybridization revealed intense signals for both
      biglycan and alpha1(I) collagen mRNA on day 2 in the spindle-shaped mesenchymal
      cells located between the surviving myocytes in the infarct peripheral zone. On
      day 7, biglycan mRNA signals were observed in the interior of the infarct around
      the infarct granulation tissue, a distribution that was essentially the same as
      that of alpha1(I) collagen. These results demonstrated that the increases in the
      infarct biglycan mRNA expression produced by mesenchymal cells (presumably
      myofibroblasts and fibroblasts) was closely co-localized with that of type I
      collagen mRNA, indicating that biglycan contributes to the infarct healing
      processes.

PMID- 9769231
TI  - Abnormal mitochondrial function in myocardium of dogs with chronic heart failure.
AB  - Chronic heart failure (HF) is associated with morphologic abnormalities of
      cardiac mitochondria that include hyperplasia, reduced organelle size and
      compromised structural integrity. In the present study, we examined mitochondrial
      respiration in myocardium of 10 normal dogs and 10 dogs with chronic HF (LV
      ejection fraction 24+/-2%) produced by intracoronary micro-embolizations.
      Mitochondrial respiratory rates were determined using a Clark electrode in an
      oxygraph cell containing saponin-skinned muscle bundles. Basal respiratory rate
      (VO), respiratory rate after addition of substrates, glutamate and malate (VSUB)
      and state 3 respiratory rate (VADP, after addition of ADP), were measured in
      tissue samples from the subendocardial and subepicardial LV free wall,
      interventricular septum and right-ventricular free wall. No differences were
      observed in basal respiratory rates between normal and HF tissue, while VSUB was
      significantly lower in HF compared to normal. VADP was 50-60% lower in HF
      compared to normal tissue (P<0.001). The results indicate abnormal mitochondrial
      respiratory activity in myocardium of dogs with chronic HF. These findings
      support the concept of low myocardial energy production in HF that can contribute
      to the global cardiac dysfunction.

PMID- 9769232
TI  - The cardiac content of sarcoplasmic reticulum in the rat determined by calcium
      uptake rate, calcium oxalate capacity, ryanodine binding and thapsigargin
      titration.
AB  - The amount of cardiac sarcoplasmic reticulum in rat hearts was estimated by
      comparing marker activities in the isolated SR fraction with their activities in
      the homogenate. Four distinguishable markers were measured: the oxalate-supported
      rate of calcium uptake, the calcium oxalate capacity, 3H-ryanodine binding and
      the thapsigargin equivalents. The calcium uptake rate and capacity and
      thapsigargin equivalents were determined in the presence and absence of SR Ca2+
      channel blockade with high concentrations of ryanodine. All of these activities
      are believed to be located only in the SR. However, the calculation of the heart
      content of SR was somewhat different for the four markers. The calcium uptake
      rate gave 8.4 mg SR protein per g tissue in the absence of ryanodine, and 9.6 mg
      per g in its presence; calcium oxalate capacity gave similar numbers, 9.9 mg per
      g in the absence of ryanodine and 8.0 mg per g in its presence. The thapsigargin
      titration gave similar equivalent with or without ryanodine, indicating that the
      homogenate contained about 8.0 mg of SR per g tissue. Using 3H-ranodine binding
      as a marker, the cardiac content of SR was calculated to be 16.7 mg per g. These
      differences are attributed to the non-ideal behavior of these markers. Some of
      the Ca2+ uptake activity is not thapsigargin sensitive, and some of the 3H
      ryanodine binding does not fractionate with the SR Ca2+ uptake activity.

PMID- 9769233
TI  - Regional myocyte hypertrophy parallels regional myocardial dysfunction during
      post-infarct remodeling.
AB  - After large myocardial infarction (MI), left-ventricular (LV) remodeling is
      characterized by cavity dilatation, eccentric hypertrophy, and regional
      mechanical dysfunction. We wished to correlate cellular hypertrophy chronically
      after MI with in vivo function on a regional basis within non-infarcted
      myocardium. Twelve sheep were studied. Seven underwent coronary ligation to
      create an anteroapical MI. Magnetic resonance imaging (MRI) was performed once in
      controls, and prior to and 8 weeks after infarction, for measurement of LV mass,
      volumes, ejection fraction, and regional intramyocardial circumferential
      shortening (%S). Myocyte morphometric indices (cell volume, length, cross
      sectional area, width, and length/width ratios) were measured from myocytes
      isolated from regions adjacent to (within 2 cm of the infarct border) and remote
      from the infarct and at corresponding loci in the control animals. From baseline
      to 8 weeks after infarction in the infarcted animals, end-diastolic volume
      increased from (mean+/-s.d.) 1.9+/-0.4 ml/kg to 2.6+/-0.4 ml/kg (P<0.02) and EF
      fell from 49+/-6 to 35+/-6% (P<0.02). LV mass trended upwards from 2.2+/-0.4 to
      2.6+/-0.4 g/kg (P=n.s.). Regionally, %S in the region adjacent to the infarct
      fell (from 19+/-3 to 13+/-3%, P<0.003) while remote %S did not change. Cell
      volume in adjacent non-infarcted regions was greater than that in remote non
      infarcted regions (3.8+/-0.9x10(4) micrometer3 v 2.6+/-0. 8x10(4) micrometer3,
      P<0.006) and this difference (+1.2+/-0.7x10(4) micrometer3) was greater than the
      corresponding regional difference in controls (+0.4+/-0.2x10(4) micrometer3,
      P<0.05). Similarly, myocytes in adjacent non-infarcted regions were longer
      (138.0+/-10.1 micrometer) than in remote regions (123.7+/-10.1 micrometer,
      P<0.002), and this difference (+14.3+/-7.2 micrometer) was greater than that in
      controls (-1.4+/-5.6 micrometer, P<0.003). Adjacent %S correlated inversely with
      adjacent myocyte cell volume (r=-0.72, P<0.009) and cell length (r=-0.70,
      P<0.02). In mechanically dysfunctional non-infarcted regions adjacent to chronic
      transmural myocardial infarction in the remodeled LV, disproportionate cellular
      hypertrophy occurs, predominantly due to an increase in cell length. Mechanical
      dysfunction in these regions correlates with cell lengthening and hypertrophy.

PMID- 9769234
TI  - Depressed myofilament co-operativity associated with post-cardioplegic myocardial
      depression.
AB  - The mechanism underlying myocardial depression after procedures involving
      cardioplegia are unknown. We tested the hypothesis that such depression was
      associated with altered myofilament interactions, using isolated hearts perfused
      with warm (37 degreesC), oxygenated (95% O2/5% CO2) Krebs-Ringer's bicarbonate
      (KRB) buffer. A latex balloon was inserted into the left ventricle (LV) to
      monitor LV function. All hearts underwent a 30-min equilibration period. One
      group of hearts (CPL+RPR) were arrested with St Thomas #2 cardioplegic solution
      (4 degreesC; 3 ml followed by 1 ml every 15 min) for 120 min, followed by
      reperfusion with warm, oxygenated KRB. A second group underwent cardioplegic
      arrest with no reperfusion (CPL). A third group underwent 60 min of warm,
      oxygenated perfusion with KRB beyond the equilibration period (60 MIN). The last
      group only underwent the equilibration period (EQUIL). LV function was assessed
      at the end of equilibration, and at 30 and 60 min of reperfusion (or 30 and 60
      min additional perfusion in the 60 MIN group). All hearts were frozen at the end
      of the temporal protocol for each group, and stored at -70 degreesC for later
      measurement of Ca2+-stimulated Mg2+ ATPase activity after isolation of
      myofibrils. CPL+RPR hearts demonstrated significant depression of systolic
      pressure and elevation diastolic pressure at fixed volumes, compared to baseline
      and 60 MIN group values. There were no significant changes in the amount of
      constituent myofilament proteins, as assessed by densinometric analyses of
      Western blots. There were also no changes in the minimal or maximal ATPase
      activities, nor in the pCa50, indicating no effect of cardioplegic arrest on
      myofilament sensitivity to calcium. However, all hearts that underwent
      cardioplegic arrest were found to have significantly lower Hill coefficients
      (1.85+/-0.09 and 1.85+/-0.13 v 2.31+/-0.13 and 2.34+/-0. 14 in CPL+RPR and CPL v
      60 MIN and EQUIL hearts, respectively), suggesting decreased co-operativity of
      the actomyosin interaction. Such a decrease in co-operativity would contribute to
      both the systolic and diastolic alterations associated with myocardial depression
      after cardioplegic arrest. These changes were associated with the cardioplegic
      event, and appeared to be independent of reperfusion.

PMID- 9769235
TI  - Oxidative stress induces DNA fragmentation and caspase activation via the c-Jun
      NH2-terminal kinase pathway in H9c2 cardiac muscle cells.
AB  - The aim of this study was to test the hypothesis that oxidative stress induces
      apoptosis in the H9c2 cardiac muscle cell line, and that signaling via mitogen
      activated protein kinase (MAPK) pathways is involved. Three forms of oxidative
      stress were utilized: the superoxide generator menadione; hydrogen peroxide; or
      simulated ischemia followed by reperfusion. Relatively low concentrations of
      menadione (10 micrometer) or H2O2 (250 micrometer) caused maximal DNA
      fragmentation and caspase activation, both markers for apoptotic cell death, and
      preferential activation of the c-Jun NH 2-terminal kinase (JNK) and p38 MAPK
      pathways. In contrast, higher concentrations of menadione or H 2O2 caused less
      DNA fragmentation, more necrotic cell death and preferential activation of the
      extracellular signal-regulated kinase (ERK) pathway. Simulated ischemia alone did
      not induce DNA fragmentation or caspase activation and activated only the p38
      MAPK pathway. However, ischemia plus reperfusion resulted in DNA fragmentation,
      caspase activation, necrotic cell death and activation of all three MAPK
      pathways. Selective inhibition of the ERK or p38 MAPK pathways (by PD98059 or SB
      203580, respectively) had no effect on the extent of oxidative stress-induced DNA
      fragmentation or caspase activation. In contrast, inhibition of the JNK pathway
      by transfection of a dominant negative mutant of JNK markedly reduced the extent
      of DNA fragmentation and caspase activation induced by oxidative stress. In
      conclusion, these data suggest that the JNK pathway plays an important role in
      signaling oxidative stress-induced apoptosis of H9c2 cardiac muscle cells.

PMID- 9769236
TI  - Modulation of adenosine effects in attenuation of ischemia and reperfusion injury
      in rat heart.
AB  - We investigated whether xanthine oxidase-derived superoxide radical generation
      could be modified by interfering with adenosine transport and metabolism in
      reducing myocardial injury during post-ischemic reperfusion. Isolated rat hearts
      perfused at constant pressure were subjected to 20 min of pretreatment with test
      agents, followed by 40 min global ischemia and 30 min reperfusion with or without
      test agents. In hearts treated with adenosine deaminase inhibitor, erythro 9-(2
      hydroxy-3-nonyl) adenine (EHNA), alone or together with a selective nucleoside
      transport blocker, p-nitrobenzylthioinosine (NBMPR), the accumulated amount of O
      2. was significantly reduced [10.2+/-0.97, 11.6+/-2.4, 8.1+/-0.51, respectively,
      v 31.6+/-2.1 (s. e.) nmol/wet g/30 min in ischemic control, P<0.01]. A positive
      correlation between O-2. and inosine release was observed in the initial 5 min of
      reperfusion in hearts treated with either EHNA or NBMPR ( r=0.475, P<0.05).
      Furthermore, the accumulated amount of LDH release showed positive correlation
      with that of O-2. among the same groups (r=0.474, P<0.05). Both EHNA and NBMPR
      had the cardioprotective effect on the recovery of left ventricular end-diastolic
      pressure (LVEDP), ATP repletion, and build up of endogenous adenosine. This study
      suggests that : (1) adenosine metabolism can be manipulated towards the formation
      of O-2. during reperfusion, and it has an important bearing on the cardiac
      recovery of ischemic myocardium, (2) the generation of O-2. is related to only
      inosine release during initial reperfusion.

PMID- 9769237
TI  - Terikalant, an inward-rectifier potassium channel blocker, does not abolish the
      cardioprotection induced by ischemic preconditioning in the rat.
AB  - Recent results have shown that the sulfonylurea receptor couples to several types
      of inward-rectifier potassium (KIR) channels, which suggests that sensitivity to
      blockade of a pathophysiological phenomenon such as ischemic preconditioning (PC)
      by glibenclamide may not be the result of this compound selectively blocking the
      ATP-sensitive potassium (KATP) channel. Therefore, to address this possibility, a
      role for myocardial KIR v KATP channels in ischemic PC was evaluated in the rat.
      To test this hypothesis, anesthetized, open-chest, male Wistar rats were assigned
      to one of seven experimental protocols. Animals assigned to group I (control)
      received 30 min of occlusion and 2 h of reperfusion. Ischemic PC was produced by
      3x5-min occlusion and 2-h reperfusion periods (group II). Terikalant (TK), an
      inward-rectifier potassium channel blocker, was used to test the role of other K+
      channels, most notably the KIR, in the cardioprotective effect of ischemic PC in
      the rat. TK was given at a dose of 3 mg/kg, i.v., 15 min before the prolonged
      occlusion and reperfusion periods (group III). In groups IV, V, and VI terikalant
      (1, 3 and 6 mg/kg, i.v.) was given 15 min before ischemic PC (lowTK+PC, medTK+PC
      and hiTK+PC, respectively). Group VII consisted of glibenclamide (0.3 mg/kg,
      i.v.) given 30 min prior to ischemic PC (GLY+PC). Infarct size (IS) as a percent
      of the area at risk (AAR) was measured using the histochemical stain, 2,3, 5
      triphenyltetrazolium chloride. The average IS/AAR for the control was 49.9+/
      2.1%. Ischemic PC markedly reduced infarct size (8.6+/-1. 8%; * P<0.05 v
      control). Terikalant (TK; 1, 3 and 6 mg/kg, i.v.) did not abolish the
      cardioprotective effect of ischemic PC at any dose (15.5+/-6.4, 16.4+/-5.2 and
      8.8+/-1.6%, respectively; * P<0.05 v control). TK itself had no effect on infarct
      size. GLY completely abolished the cardioprotective effect of ischemic PC (48.2+/
      6.4%). In addition, the high dose of TK significantly (P<0.05) increased the
      action potential duration at 50% repolarization from 48+/-3 to 64+/-4 ms and 30
      microM of TK, a concentration which produced a 39% decrease in the inward
      rectifier potassium channel current in isolated guinea-pig ventricular myocytes
      in the whole-cell patch-clamp mode did not block the increase in K ATP current
      produced by the KATP opener bimakalim (3 microM). These results demonstrate that
      although the myocardial KATP channel belongs to the K IR superfamily, the
      endogenous myocardial KIR channel does not mediate ischemic PC in the rat heart;
      however, the K ATP channel does mediate its cardioprotective effect.

PMID- 9769238
TI  - Cardiac-specific overexpression of alpha1BAR regulates betaAR activity via
      molecular crosstalk.
AB  - alpha1AR play an important role in regulating cardiac contractility under many
      physiological and pathological conditions. We are thus interested in determining
      the molecular events coupled to alpha1AR signalling pathways in the heart and in
      the possibility of molecular crosstalk between different receptor systems. We
      have analysed transgenic mouse lines which overexpress the wild-type (WT)
      alpha1BAR (3.0+/-0.26 pmol/mg, TgA and 2.1+/-0.26 pmol/mg, TgB) compared to non
      transgenic animals (0.02+/-0.002 pmol/mg). Ligand binding studies showed that
      overexpression of alpha1BAR did not affect the betaAR density or their affinity
      for a specific antagonist. Basal adenylyl cyclase activity, but not basal cAMP
      levels, was increased in the transgenic animals, while isoproterenol-mediated
      fold stimulation of adenylyl cyclase activity of both transgenic mouse lines was
      decreased significantly. In addition, high-affinity betaAR agonist binding was
      severely impaired in the transgenic animals. We found increases in the amount of
      two Ca2+-independent (delta and epsilon) and one Ca2+-dependent (betaII) protein
      kinase (PKC) isoforms associated with the particulate fraction, suggesting that
      PKC may be involved in the heterologous desensitization of betaAR by alpha1BAR.
      These results indicate that following alpha1BAR overexpression, the betaAR system
      may be uncoupled via molecular crosstalk.

PMID- 9769239
TI  - Role of microtubules in the viscoelastic properties of isolated cardiac muscle.
AB  - Myocardial viscoelastic properties are determined by both interstitial collagens
      and intramocyte structures, including sarcolemma, contractile proteins and the
      cytoskeleton. It is not known whether myocyte microtubules are significant
      constituents that contribute to the viscoelastic properties of cardiac muscle. We
      examined the passive properties of isolated right-ventricular papillary muscles
      before and after altering the polymerization states of microtubules. The muscles
      were subjected to sinusoidal changes in length (strain) and the resultant changes
      in resting tension (stress) were measured. The elastic constant was determined by
      the slope of the stress-strain relation during the slow increase in muscle length
      (duration 60 s). The viscous constant was determined by the loop area between the
      stress-strain relation obtained during the rapid increase and decrease in muscle
      length (duration 1 s). Colchicine (1 micromol/l, 1 h), which depolymerized
      microtubules, had little effect on either the elastic constant or viscous
      constant. In contrast, taxol (10 micromol/l), which hyperpolymerized and
      stabilized microtubules, exerted a time-dependent increase in the viscous
      constant (133+/-9% of control; n=9, P<0.05), but did not affect the elastic
      constant (18. 9+/-2.2 to 17.7+/-2.1; n=7, P=n.s.). The increase of viscosity by
      taxol closely paralleled the increase in the strain rate. The specificity of each
      pharmacological intervention for the microtubule polymerization state was
      confirmed by both a Western blot analysis and the immunofluorescence micrographs
      of myocyte tubulin. Like other cytoskeleton and extracellular collagens, the
      increase in the myocyte microtubule density was able to modify the viscous
      component of the passive properties of the isolated cardiac muscle.

PMID- 9769240
TI  - The effect of the oxidant hypochlorous acid on the L-type calcium current in
      isolated ventricular cardiomyocytes.
AB  - Disturbances of cellular calcium homeostasis due to oxidative stress are involved
      in reperfusion associated phenomena like myocardial stunning and reperfusion
      induced arrhythmias. This study investigates the effect of the major neutrophil
      derived oxidant hypochlorous acid (HOCl) on the l-type calcium current (ICa,L) of
      hamster ventricular cardiomyocytes. Using the whole-cell recording configuration
      of the patch-clamp technique, I Ca,L was recorded over 12.5 min (0.1 Hz).
      Application of HOCl or buffer (for control) via a second micropipette in close
      proximity to the cell was started at t=1 min. To study the influence of increased
      intracellular calcium buffer concentration and of ATP on HOCl-induced effects,
      internal solutions were composed as follows (EGTA/ATP in mmol/l): group I
      (standard) 0.5/0.0, group II 5.0/0.0, group III 0.5/1.0, and group IV 5.0/1.0.
      Application of 10, 20 and 40 micromol/l HOCl (under group I-conditions) caused a
      dose-dependent decrease in peak ICa,L to 82+/-3.2, 66+/-4.2 and 36+/-4.3% of
      baseline value (v 94+/-4.8% in controls, mean+/-s.e.m., P<0.05), and integrated
      ICa,L without affecting apparent reversal potential, activation and inactivation
      kinetics. HOCl-induced (40 micromol/l) decrease in ICa,L was partially inhibited
      in group II and III. Peak currents of these groups averaged 51+/-4.7 and 52+/
      4.2% of baseline after 11.5 min administration of HOCl. Peak current in group IV
      cells decreased to 65+/-3.8% of baseline value (P<0.05 between group I-IV and v
      controls). Oxidative stress-induced decrease in ICa,L may be explained by energy
      depletion or calcium overload rather than by direct oxidative inactivation of
      channel proteins. A decrease in ICa, L may contribute to the shortening of action
      potential during reperfusion.

PMID- 9769241
TI  - Improved myocardial tolerance to ischaemia in the diabetic rabbit.
AB  - Because cardiac complications after myocardial infarction are more frequent in
      diabetics, we tested whether experimentally-induced diabetes may increase
      ischaemic myocardial injury in 23 rabbits. Diabetes was induced in randomized
      rabbits with the alloxan method. After 2 months, diabetic rabbits underwent a 30
      min coronary occlusion followed by 3-h reperfusion and were compared with
      controls. Collateral flow was measured by the radioactive microsphere technique
      and infarct size by tetrazolium staining. Infarct size represented 28.6+/-4% of
      area-at-risk in controls and 16.5+/-3% in diabetics (P<0.05). Collateral flow
      (0.06+/-0.03 ml/min/g in controls and 0.014+/-0.004 ml/min/g in diabetics) and
      area-at-risk (50.2+/-4.2% of left ventricle in controls and 53.9+/-5. 4% in
      diabetics) were similar in both groups. There was a significant positive
      correlation between area-at-risk and infarct size in both groups (r=0.60 and
      0.70, respectively) and for a given area-at-risk, diabetic rabbits developed
      smaller myocardial infarction than controls (covariance analysis, P<0.01). In
      additional experiments, hyperglycemia induced by intravenous glucose infusion in
      non-diabetic rabbits did not protect the ischaemic myocardium (infarct size:
      37.9+/-12.5%). In conclusion, diabetes in the rabbit induces a chronic and
      metabolic form of preconditioning. Further studies are needed to explore the
      mechanism and time course of this protection.

PMID- 9769242
TI  - Changing patterns of gene expression in the pulmonary trunk-banded rat heart.
AB  - A pressure-overload model in the rat by banding the pulmonary trunk (PT) was
      developed to investigate alterations in gene expression in left- and right
      ventricular compartments during the transition from compensated right-ventricular
      (RV) hypertrophy to right heart failure. Right heart failure in rat is
      characterized by liver cirrhosis, hydrothorax and ascites. The diameter of
      constriction was found to determine the time course of heart failure development.
      Only the RV free wall and the right atrium increased in weight, without a
      difference between compensated and failing RV. An increase in circulating ANP
      revealed a hypertrophic response of the myocardium, while increased circulating
      ammonia levels discriminated between compensated hypertrophy and failure. As
      parameters for stress, fibrosis and Ca2+-handling, changes in the pattern and
      level of the mRNAs encoding atrial natriuretic peptide (ANP), collagenIIIalpha1,
      and sarcoplasmic endoplasmic reticular calcium ATPase 2 (SERCA2), phospholamban
      (PLB) and calsequestrin (CSQ) were studied by Northern blot and in situ
      hybridization analyses. Pulmonary trunk banding resulted in an induction of ANP
      mRNA, a moderate increase in collagenIII alpha1 mRNA and a decrease in SERCA2 and
      PLB mRNA levels in both the left and right ventricles, but changes were most
      pronounced in the myocardium surrounding the RV cavity. Increased ammonia blood
      levels are a promising prognostic marker to detect the development of right heart
      failure.

PMID- 9769243
TI  - Effect of chronic severe diabetes on myocardial stunning in the dog.
AB  - In this study, we examined whether chronic severe diabetes may affect ischaemic
      and post-ischaemic regional myocardial dysfunction in vivo in the dog. Diabetes
      was chemically induced in randomized animals and major metabolic alterations were
      observed confirming the severity and chronicity of the diabetes. After 70 days,
      halothane-anaesthetized dogs underwent a 20-min coronary occlusion, followed by
      reperfusion. During ischaemia, global left ventricle function (dP/dtmax) was more
      altered (P<0.005) in diabetics ( n=10) than in controls (n=10), whereas area-at
      risk (29+/-2.5% of the left ventricle in diabetics v 32.4+/-1.9% in controls) and
      ischaemic subendocardial myocardial blood flow (radioactive microsphere
      technique, 0.11+/-0.02 v 0.10+/-0.03 ml/min/g) were similar. During reperfusion,
      both groups developed significant (P<0.05) regional myocardial dysfunction
      (somomicrometry, 41+/-14% of baseline in controls and 66+/-8% in diabetics),
      whereas the difference between groups was not significant. No dog of either group
      developed myocardial cell necrosis on tissue histology. Multivariate analyses,
      including the severity of prior ischaemia and the occurrence of ventricular
      fibrillation as covariables, confirmed that myocardial stunning was not increased
      in diabetics, although ischaemia was clearly less-well-tolerated in diabetic dogs
      as global (dP/dtmax) as well as regional myocardial function were significantly
      (P<0.05) more altered in diabetics during ischaemia. Whilst alteration of
      arachidonate and cholesterol metabolism may partly explain this apparent paradox,
      further studies are required to resolve this issue.

PMID- 9769244
TI  - Trypanosoma cruzi: detection of a surface antigen cross-reactive to human C
      reactive protein.
AB  - C-reactive protein (CRP) is an acute phase protein secreted by liver hepatocytes,
      and is also found on the surface of lymphocytes and as a membrane-associated
      protein expressed on rat liver macrophages and human monocytes. C-reactive
      protein levels increase in the sera of children infected with Trypanosoma cruzi,
      during the acute phase of Chagas' disease, but its role in the course of this
      infection is unknown. Experiments designed to detect the binding of CRP to
      circulating forms of T. cruzi failed to observe it because anti-human CRP
      antibodies bind to the parasite. The present work intended to further clarify
      this novel question related to the anti-CRP cross-reactivity with the parasite.
      Indirect immunofluorescence, immunoenzymatic, flow cytometry, and Western blot
      assays showed that three different polyclonal anti-human CRP antibody
      preparations bind to T. cruzi surface. This binding is dose-dependent, saturable,
      and is inhibited when anti-CRP antibodies from different species were allowed to
      compete, indicating the specificity of the reactivity. The antibodies recognized
      a protein band below 23 kDa in Western blot analysis of parasite extracts. The
      divalent cation chelators EDTA and EGTA impaired the antigen recognition by the
      antibodies. The binding to parasite surface was also observed with some available
      monoclonal antibodies raised against human CRP. A polyclonal anti-human CRP
      presented an inhibitory effect on invasion of heart muscle cells by T. cruzi. Our
      results indicate that a molecule antigenically related to CRP, a possible CRP
      like molecule, is expressed on the surface of T. cruzi.

PMID- 9769245
TI  - The host-protein-independent iron uptake by Tritrichomonas foetus.
AB  - Iron uptake from a low-molecular-weight chelate Fe(III)-nitriloacetate (Fe-NTA)
      by anaerobic protozoan parasite Tritrichomonas foetus was investigated and
      compared with that from iron-saturated lactoferrin and transferrin. The results
      showed that the iron uptake from Fe-NTA was saturable (Km = 2.7 microM, Vmax =
      21.7 fmol. microg-1.min-1) and time, and temperature dependent, thus suggesting
      involvement of a membrane transport carrier. The accumulation of iron from 59Fe
      NTA was inhibited by NaF and iron chelators. Amilorid and inhibitors of endosome
      acidification did not influence the process. Ascorbate stimulated the uptake
      while a membrane impermeable chelator of bivalent iron (bathophenanthroline
      disulfonic acid) was inhibitory, suggesting that prior to transport iron is
      reduced extracellularly. In accord with this assumption, the reduction of ferric
      to ferrous iron in the presence of intact T. foetus cells was demonstrated.
      Dynamics and properties of uptake of iron released from transferrin were similar
      to those from Fe-NTA, indicating involvement of common mechanisms. Iron uptake
      from lactoferrin displayed profoundly different characteristics consistent with
      receptor-mediated endocytosis. Metronidazole-resistant derivative of the
      investigated T. foetus strain showed marked deficiency in iron acquisition from
      Fe-NTA and transferrin while its iron uptake from lactoferrin was higher than
      that of the parent strain. The results presented show that T. foetus possesses at
      least two independent mechanisms that mediate acquisition of iron.

PMID- 9769246
TI  - Plasmodium falciparum: heterologous synthesis of the transmission-blocking
      vaccine candidate Pfs48/45 in recombinant vaccinia virus-infected cells.
AB  - With the aim of developing transmission-blocking vaccines based on the sexual
      stage-specific surface antigen Pfs48/45 of the human malaria parasite Plasmodium
      falciparum, the gene encoding Pfs48/45 was incorporated into the genome of a
      recombinant vaccinia virus. In virus-infected mammalian tissue culture cells,
      recombinant Pfs48/45 antigen (rPfs48/45) is posttranslational modified to produce
      a highly N-glycosylated polypeptide. The rPfs48/45 protein was radiolabeled with
      ethanolamine, consisting of a further posttranslational modification in the form
      of a glycosylphosphatidylinositol anchor at its carboxy-terminal end. The
      rPfs48/45 was not detected on the surface of the infected cells; instead, it
      remained within the secretion pathway of mammalian cells irrespective of the
      duration of infection or culture temperature. Studies with monoclonal antibodies
      specific for disulfide band-dependent epitopes of Pfs48/45 revealed that
      recombinant Pfs48/45 is not folded in its authentic conformation even if N
      glycosylation was chemically inhibited. Infection of mice and rabbits with
      recombinant virus elicited Pfs48/45-specific antibodies; however, the antisera
      failed to block parasite transmission in a standard mosquito membrane-feeding
      assay.

PMID- 9769247
TI  - Trichomonas vaginalis: expression and characterisation of recombinant S
      adenosylhomocysteinase.
AB  - The gene encoding S-adenosylhomocysteinase activity (S-adenosylhomocysteine
      hydrolase, SAHH; EC 3.3.1.1) in Trichomonas vaginalis has been expressed in
      Escherichia coli to facilitate the characterisation of the enzyme. Expression of
      this gene using the pQE-30 (6xHis N-terminal tag) expression system (QIAGEN) has
      enabled the one-step purification of 6 mg of active recombinant enzyme from a 100
      ml bacterial culture by affinity chromatography using a nickel-NTA matrix. The
      recombinant enzyme has a molecular weight of approximately 56,000 and
      identification of tryptic peptides by matrix-assisted laser desorption ionisation
      (MALDI) mass spectrometry has shown that the purified recombinant protein is
      identical in primary structure to the predicted sequence. The presence of the N
      terminal 6xHis tag in the recombinant enzyme did not appear to affect its kinetic
      and other properties, which are similar to those exhibited by the "native" enzyme
      present in cell-free extracts of T. vaginalis. These properties include a similar
      apparent Km for adenosine (20-25 microM for the recombinant and 5-10 microM for
      the native enzymes, respectively) and similar inhibition/inactivation patterns
      exhibited by adenosine analogues such as arabinosyl adenine (ara-A).

PMID- 9769248
TI  - Crithidia luciliae: functional expression of nucleoside and nucleobase
      transporters in Xenopus laevis oocytes.
AB  - The expression of purine-specific nucleoside and base transporters of Crithidia
      luciliae has been demonstrated in Xenopus laevis oocytes. Poly(A)+-mRNA from C.
      luciliae, cultured in either purine-replete or purine-starved conditions, was
      microinjected into X. laevis oocytes. For "purine-replete" mRNA, expression of
      adenosine and hypoxanthine uptake in microinjected X. laevis oocytes was
      increased on average 9- and 3-fold above water-injected controls, respectively.
      Expression of adenosine and hypoxanthine uptake in oocytes microinjected with
      "purine-starved" mRNA was 8 and 3-fold above water-injected controls,
      respectively. Substrate competition indicated an adenosine/deoxyadenosine
      transporter and a separate base transporter specific for hypoxanthine. In
      contrast to C. luciliae in vivo, where the level of activity of adenosine and
      hypoxanthine transport was regulated by the level of purines in the medium, the
      heterologous expression of these transporters (from both purine replete and
      deplete cultures) in X. laevis oocytes was independent of the extracellular
      purine concentration. These results may suggest that the presence of specific
      transporter message is independent of the extracellular purine content,
      indicating that the regulation of activation and expression of these transporters
      in C. luciliae may not be under transcriptional control.

PMID- 9769249
TI  - Sequence and functional analysis of the intergenic regions separating babesial
      rhoptry-associated protein-1 (rap-1) genes.
AB  - The rhoptry-associated protein 1 (RAP-1) expressed by all babesial parasites is
      encoded by tandemly arranged genes separated by discrete intergenic (IG) regions.
      We hypothesize that these IG regions regulate rap-1 gene expression. In Babesia
      bovis two identical rap-1 gene copies are separated by a 1.0-kb noncoding region
      which is also exactly conserved 5' to the rap-1 gene 1. In contrast, the complex
      B. bigemina rap-1 locus contains at least 5 polymorphic rap-1a genes separated by
      uncharacterized 3.38-kb regions. A genomic clone encoding the 3' sequence of rap
      1 gene copy 1, the 1 kb IG region, and the 5' sequence of gene copy 2 was
      obtained by PCR amplification of DNA from the Mo7 biological clone of B. bovis
      and sequenced. This was follow by amplification and sequence analysis of the 3.38
      kb region separating two B. bigemina rap-1a genes, revealing the presence of two
      different IG regions denominated IG-1 (0.7 kb) and IG-2 (1.3 kb), flanking a
      newly identified rap-1b orf. Sequence analysis and comparison among babesial rap
      1 IG regions from B. bovis, B. bigemina, B. canis, and B. ovis revealed
      conservation of at least three putative regulatory boxes consistently positioned
      5' of the start of the rap-1 orfs. To determine whether rap-1 IG regions
      contained a functional promoter, the entire 1-kb IG region from B. bovis was
      cloned into pCAT, a promoterless plasmid containing the cat gene. The IG region
      in the 5' --> 3' orientation strongly promoted transcription in vitro by
      homologous B. bovis RNA polymerases. The presence of conserved regions 5' to each
      rap-1 gene copy and among other babesial rap-1 IG regions and the in vitro
      promoter function in the 5' --> 3' orientation support a role for the IG region
      in rap-1 gene regulation.

PMID- 9769250
TI  - Cryptosporidium parvum: PCR-RFLP analysis of the TRAP-C1 (thrombospondin-related
      adhesive protein of Cryptosporidium-1) gene discriminates between two alleles
      differentially associated with parasite isolates of animal and human origin.

PMID- 9769251
TI  - Plasmodium gallinaceum: use of antisera to degenerate synthetic peptides derived
      from the active site of protozoal chitinases to characterize an ookinete-specific
      chitinase.

PMID- 9769253
TI  - Functional consequences of lung volume reduction surgery for COPD.

PMID- 9769254
TI  - Effect of lung volume reduction surgery on gas exchange and pulmonary
      hemodynamics at rest and during exercise.
AB  - Lung volume reduction surgery (LVRS) has become an extended surgery for emphysema
      in order to improve the dyspnea of severely affected patients. Because resection
      of lung areas may reduce the vascular bed, which is an important factor of
      pulmonary hypertension in emphysematous patients, especially during exercise, the
      aim of our study was to assess the outcome of pulmonary hemodynamics and gas
      exchange at rest and during exercise after LVRS. Nine patients had right heart
      catheterization before and 3 to 12 mo (mean, 4.5 mo) after LVRS. FEV1 increased
      from 705 to 1,005 ml (p < 0.05) after LVRS. PaO2, PaCO2 and mean pulmonary artery
      pressure (Ppa) did not change after LVRS, either at rest or during exercise.
      However, a significant overall decrease of the respiratory swings of the
      pulmonary artery diastolic pressure (DeltaPd) at rest (median value, from 12 to 8
      mm Hg, p < 0.01) and during exercise (from 20 to 15 mm Hg, p < 0.05) was
      observed. There was a significant correlation between the change in resting Ppa
      (Ppa before minus Ppa after LVRS) and the change in resting DeltaPd (r = 0.73, p
      < 0.03), and also between the change in exercising Ppa and the change in resting
      DeltaPd (r = 0.80, p < 0.02). Significant correlations were also found between
      the change in exercising Ppa and the change in exercising PaO2 (r = -0.70, p <
      0.05), and between the change in exercising Ppa and the change in exercising
      PaCO2 (r = 0.76, p < 0. 03). We conclude that pulmonary hemodynamics in most
      cases are not impaired by LVRS either at rest or during exercise. The possible
      mechanisms influencing hemodynamics after a lung volume reduction procedure are
      discussed.

PMID- 9769255
TI  - Prediction of clinical severity and outcome of ventilator-associated pneumonia.
      Comparison of simplified acute physiology score with systemic inflammatory
      mediators.
AB  - Systemic kinetics of three inflammatory mediators (bactericidal/permeability
      increasing protein [BPI], soluble intercellular adhesion molecule [sICAM], and
      soluble E-selectin [sE-selectin]) were studied during the development of
      ventilator-associated pneumonia (VAP) (n = 42), diagnosed on quantitative
      cultures of bronchoscopic samples. From a pool of collected samples, nested
      samples were used to measure mediators on Days -4, -2, 0, and +2, relative to
      diagnosis. Correlations between systemic levels of mediators and clinical
      severity of infection (VAP with or without severe sepsis or septic shock) and
      patient outcome (mortality at Day 10 after diagnosis) were studied. Predictive
      values of inflammatory mediators were compared with daily Simplified Acute
      Physiology Score II (SAPS II) values and the logarithmic number of bacteria in
      bronchoscopic samples. During the development of VAP, increasing SAPS II scores
      and rising systemic mediator levels were only found in patients in whom VAP was
      accompanied with severe sepsis or septic shock. Values of SAPS II and plasma
      levels of BPI and sE-selectin, but not sICAM, increased from the day of diagnosis
      on in patients who died within 10 d of diagnosis. Systemic levels of inflammatory
      mediators did not better predict clinical severity or patient outcome than daily
      SAPS II scores. The logarithmic number of bacteria in bronchoscopic samples
      poorly correlated with circulating levels of inflammatory mediators, severity of
      infection, and patient outcome. Our findings show that a clinical scoring system
      (SAPS II score) is at least as good as a predictor for the clinical severity of
      infection and patient outcome, and provide new information on the kinetics of
      inflammatory mediators during the development of VAP.

PMID- 9769256
TI  - Relationship between exhaled nitric oxide and childhood asthma.
AB  - The purpose of the study was to determine if exhaled nitric oxide levels in
      children varied according to their asthmatic and atopic status. Exhaled nitric
      oxide was measured in a sample of 93 children attending the North West Lung
      Centre, Manchester, United Kingdom, for the clinical evaluation of a respiratory
      questionnaire being developed as a screening tool in general practice. The
      clinical assessment included full lung function, skin prick testing, and exercise
      challenge. Children were said to be asthmatic either by consensus decision of
      three independent consultant pediatricians, who reviewed all the clinical results
      except the nitric oxide measurements, or by positive exercise test. Atopic
      asthmatic children had higher geometric mean exhaled nitric oxide levels
      (consensus decision, 12.5 ppb [parts per billion] 95% CI, 8.3 to 18. 8; positive
      exercise test, 12.2 ppb 95% CI, 7.6 to 19.7) than did nonatopic asthmatic
      children (3.2 ppb 95% CI, 2.3 to 4.6; 3.2 ppb 95% CI, 2.0 to 5.0), atopic
      nonasthmatic children (3.8 ppb 95% CI, 2. 7 to 5.5; 5.7 ppb 95% CI, 4.1 to 8.0),
      or nonatopic nonasthmatic children (3.4 ppb 95% CI, 2.8 to 4.1; 3.5 ppb 95% CI,
      3.0 to 4.1). Thus, exhaled nitric oxide was raised in atopic asthmatics but not
      in nonatopic asthmatics, and these nonatopic asthmatics had levels of exhaled
      nitric oxide similar to those of the nonasthmatics whether atopic or not.

PMID- 9769257
TI  - Public health interventions to encourage TB class A/B1/B2 immigrants to present
      for TB screening.
AB  - From 1985 to 1995 the proportion of all Santa Clara County, California (SCC),
      tuberculosis (TB) cases among recent immigrants climbed 73% (137 to 237). In SCC
      the efficient and cost-effective means encouraging TB Class A/B1/B2 immigrants
      (TBIMs) to present for TB screening and the prevalence of active TB among them
      were never investigated. We studied all TBIMs entering SCC from October 1, 1995
      to June 30, 1996, notified to SCC by the CDC's Division of Quarantine (DQ).
      Encouraging TBIMs to seek TB screening, we sent letters to them promptly on the
      DQ notification, followed sequentially by phone calls and home visits. We
      determined the outcome of screening and its cost. We screened 314 of 323 (97.2%)
      TBIMs including 79 of 323 TBIMs who presented prior to interventions, 213 of 314
      (87.3%) who responded to letters, 17 (7%) to phone calls, and 5 (2%) to home
      visits. Of 283 TBIMs screened 16 (5.7%) had active TB. To locate one TBIM cost
      $9.90 by letter, $43.25 by phone, and $129.88 by home visit. Locating one TB case
      cost $175.88 by letter, $696.26 by phone call. The prevalence of active TB in
      TBIMs is high. Our interventions resulted in low-cost TB screening and high-yield
      identification of active TB cases. We recommended that health departments develop
      a system for encouraging TBIMs to present for prompt TB screening.

PMID- 9769258
TI  - Combined use of exhaled hydrogen peroxide and nitric oxide in monitoring asthma.
AB  - Oxidative stress contributes to airway inflammation and exhaled hydrogen peroxide
      (H2O2) and nitric oxide (NO) are elevated in asthmatic patients. We determined
      the concentrations of expired H2O2 and NO in 116 asthmatic (72 stable steroid
      naive, 30 stable steroid-treated, and 14 severe steroid-treated unstable
      patients) and in 35 healthy subjects, and studied the relation between exhaled
      H2O2, NO, FEV1, airway responsiveness, and eosinophils in induced sputum. Both
      exhaled H2O2 and NO levels were elevated in steroid-naive asthmatic patients
      compared with normal subjects (0.72 +/- 0.06 versus 0.27 +/- 0.04 microM and 29
      +/- 1.9 versus 6.5 +/- 0. 32 ppb, respectively; p < 0.001) and were reduced in
      stable steroid-treated patients (0.43 +/- 0.08 microM, p < 0.05, and 9.9 +/- 0.97
      ppb, p < 0.001). In unstable steroid-treated asthmatics, however, H2O2 levels
      were increased, but exhaled NO levels were low (0.78 +/- 0.16 microM and 6.7 +/-
      1.0 ppb, respectively). There was a correlation between expired H2O2, sputum
      eosinophils and airway hyperresponsiveness (methacholine PC20). Exhaled NO also
      correlated with sputum eosinophils, but not with airway hyperresponsiveness. Our
      findings indicate that measurement of expired H2O2 and NO in asthmatic patients
      provides complementary data for monitoring of disease activity.

PMID- 9769259
TI  - High seroprevalence of Helicobacter pylori in active bronchiectasis.
AB  - Helicobacter pylori causes chronic inflammation of the gastric mucosa and has
      been identified in tracheobronchial secretions. Serum IgG against H. pylori was
      therefore measured prospectively in consecutive subjects with bronchiectasis (n =
      100; mean age +/- SD 55.1 +/- 16.7 yr), active pulmonary tuberculosis (n = 87;
      age, 57.3 +/- 19.1 yr), and healthy volunteers (n = 94; age, 54.6 +/- 7.6 yr).
      Seropositivity was found in 76.0% of bronchiectatic subjects, which was
      significantly higher than that of the control (54.3%, p = 0.001) and tuberculous
      (52.9%, p = 0.0001) groups. Multiple logistic regression, adjusted for age, sex,
      occupational social class, and number of persons living in the household, showed
      that H. pylori IgG levels of the bronchiectatic group were still significantly
      higher than that of the control (p = 0.0014) and tuberculous (p = 0.0154) groups.
      Multiple regression analysis revealed associations between H. pylori serology and
      sputum volume (p = 0.03) and age (p = 0.001) in the bronchiectatic patients, but
      not lung function indices or causes of bronchiectasis. The H. pylori
      seroprevalence in bronchiectasis was significantly (p = 0.0002) higher in
      patients who produced more (83.1%) than those who produced less than 5 ml
      sputum/24 h (58.6%). This is the first report of a high H. pylori seroprevalence
      in bronchiectasis which appears to be specific. Further studies are indicated to
      evaluate the possible pathogenic role of H. pylori in bronchiectasis.

PMID- 9769260
TI  - A new method to analyze lung compliance when pressure-volume relationship is
      nonlinear.
AB  - Changes in dynamic lung compliance during inspiration and expiration cannot be
      modeled accurately with conventional algorithms. We developed a simple method to
      analyze pressure-volume (P/V) relationships under condition of nonlinearity
      (APVNL) and tested it in a lung model with known resistance and nonlinear P/V
      relationship. In addition, pulmonary mechanics in 22 infants, 11 of them with
      nonlinear P/V relationships, were analyzed with the new method. The findings were
      compared with those obtained by a recently introduced algorithm, multiple linear
      regression analysis (MLR) of the equation of motion. The APVNL method described
      the changing compliance (C) of the lung model accurately, whereas the MLR method
      underestimated C especially in the first half of the breath. In infants the MLR
      method gave highly variable, often nonphysiological C values in the beginning of
      a breath. In contrast, the coefficient of variability of measurements obtained by
      the APVNL method was significantly smaller (p < 0.02), and the indices of model
      fit showed better agreement between calculated and observed pressure than for the
      MLR method (p < 0.02). We conclude that the APVNL method accurately describes
      nonlinear P/V relationships present during spontaneous breathing or mechanical
      ventilation. The method may be helpful in identifying and preventing pulmonary
      overdistention.

PMID- 9769261
TI  - Nitric oxide deficiency in fenfluramine- and dexfenfluramine-induced pulmonary
      hypertension.
AB  - Dexfenfluramine and fenfluramine greatly increase the risk of developing
      pulmonary hypertension (PHT). The mechanism of anorexigen-associated PHT (AA-PHT)
      and the reason PHT occurs in a minority of people exposed are unknown.
      Anorexigens are weak pulmonary vasoconstrictors, but they become potent when
      synthesis of the endogenous vasodilator nitric oxide (NO) is suppressed. We
      hypothesized NO deficiency predisposes affected individuals to develop AA-PHT. A
      prospective, case-control, study was performed on consecutive patients with AA
      PHT (n = 9). Two sex-matched control groups were selected: patients with primary
      PHT (P-PHT, n = 8) and normal volunteers (n = 12). Lung NO production (VNO) and
      systemic plasma oxidation products of NO (NOx) were measured at rest and during
      exercise. AA-PHT developed 17 +/- 6 mo after a short course of anorexigen (6 +/-
      2 mo) and was irreversible. VNO was lower in AA-PHT than in P-PHT and correlated
      inversely with PVR (p < 0.05). The apparent VNO deficiency may have resulted from
      increased oxidative inactivation of NO in patients with AA-PHT, as their NOx
      levels were elevated (p < 0.05) in inverse proportion to VNO (r2 = 0. 55; p <
      0.02). In susceptible persons, anorexigens can cause an irreversible syndrome of
      PHT, hypoxemia, and systemic vascular complications after brief exposures. These
      patients have a relative NO deficiency years after discontinuing the anorexigen,
      perhaps explaining their original susceptibility.

PMID- 9769262
TI  - Randomized controlled trial of physician-directed versus respiratory therapy
      consult service-directed respiratory care to adult non-ICU inpatients.
AB  - Although current evidence suggests that respiratory care protocols can enhance
      allocation of respiratory care services while conserving costs, a randomized
      trial is needed to address shortcomings of available studies. We therefore
      conducted a randomized controlled trial comparing respiratory care for adult non
      ICU inpatients directed by a Respiratory Therapy Consult Service (RTCS) versus
      respiratory care by managing physicians. Eligible subjects were adult non-ICU
      inpatients whose physicians had prescribed specific respiratory care services.
      Consecutive eligible patients were approached for consent, after which a blocked
      randomization strategy was used to assign patients to (1) Physician-directed
      respiratory care, in which the prescribed physician respiratory care orders were
      maintained (n = 74), or (2) RTCS-directed respiratory care, in which the
      physician's respiratory care orders were preempted by a respiratory care plan
      generated by the RTCS (n = 71). Specifically, these patients were evaluated by an
      RTCS therapist evaluator whose respiratory care plan was based on sign/symptom
      based algorithms drafted to comply with the American Association for Respiratory
      Care (AARC) Clinical Practice Guidelines. Appropriateness of respiratory care
      orders was assessed as agreement between the prescribed respiratory care plan and
      an algorithm-based "standard care plan" generated by an expert therapist who was
      blind to the patient's actual orders. The compared groups were similar at
      baseline regarding demographic features, admission diagnostic category, smoking
      status, and Triage Score (mean, 3.8 +/- 0.9 SD [RTCS] versus 3.7 +/- 1.0).
      Similarly, no differences were observed between RTCS-directed and physician
      directed respiratory care regarding hospital mortality rate (5.7 versus 5.6%),
      hospital length of stay (7.9 +/- 9.0 versus 7.7 +/- 7.3 d), total number of
      respiratory care treatments delivered (30.3 +/- 30 versus 31.6 +/- 30.5), or days
      requiring respiratory care (4.2 +/- 5.2 versus 4.1 +/- 3.6). Notably, using both
      a stringent (S) and a liberal (L) criterion for agreement, RTCS-directed
      respiratory care demonstrated better agreement with the "standard care plan" (82
      +/- 17% [S] and 86 +/- 16% [L]) than did physician-directed respiratory care (64
      +/- 21% [S] and 72 +/- 23% [L]) (p < 0.001). Finally, the true cost of
      respiratory care treatments was slightly lower with RTCS-directed respiratory
      care (mean, $235.70 versus $255.70/pt, p = 0.61). We conclude that (1) compared
      with physician-directed respiratory care, the RTCS prescribed a similar number
      and duration of respiratory care services at a slight savings (that did not
      achieve statistical significance) and without any increased adverse events; and
      (2) compared with physician-directed respiratory care, RTCS-directed respiratory
      care showed greater agreement with Clinical Practice Guideline-based algorithms.

PMID- 9769263
TI  - Early predictive factors of survival in the acute respiratory distress syndrome.
      A multivariate analysis.
AB  - To identify the potential impact of novel therapeutic approaches, we studied the
      early predictive factors of survival at the onset of acute respiratory distress
      syndrome (ARDS) in a 24-bed medical ICU of an academic tertiary care hospital.
      Over a 48-mo period, a total of 3,511 adult patients were admitted and 259
      mechanically ventilated patients met ARDS criteria, as defined by American
      European consensus conference, i.e., bilateral pulmonary infiltrates and
      PaO2/FIO2 lower than 200 without left atrial hypertension. These patients were
      randomly included in a developmental sample (177 patients) and a validation
      sample (82 patients). Demographic variables, hemodynamic and respiratory
      parameters, underlying diseases, as well as several severity scores (SAPS, SAPS
      II, OSF) and Lung Injury Score (LIS) were collected. These variables were
      compared between survivors and nonsurvivors and entered into a stepwise logistic
      regression model to evaluate their independent prognostic roles. The overall
      mortality rate was 65%. SAPS-II, the severity of the underlying medical
      conditions, the oxygenation index (mean airway pressure x FIO2 x 100/PaO2), the
      length of mechanical ventilation prior to ARDS, the mechanism of lung injury,
      cirrhosis, and occurrence of right ventricular dysfunction were independently
      associated with an elevated risk of death. Model calibration was very good in the
      developmental and validation samples (p = 0.84 and p = 0.72, respectively), as
      was model discrimination (area under the ROC curves of 0.95 and 0.92,
      respectively). Thus, the prognosis of ARDS seems to be related to the triggering
      risk factor, the severity of the respiratory illness, and the occurrence of a
      right ventricle dysfunction, after adjustment for a general severity score.

PMID- 9769264
TI  - Is the asthma quality of life questionnaire a useful measure for low-income
      asthmatics?
AB  - The purpose of this study was to evaluate the reliability and validity of the
      Asthma Quality of Life Questionnaire (AQLQ) in a population-based sample of low
      income adults with asthma. A total of 112 subjects (46 African American, 66
      Caucasian; mean age = 33 +/- 9 yr; 26% male) were recruited from the Baltimore
      County, Maryland and Atlanta, Georgia metropolitan areas. Internal consistency
      reliability (Cronbach's alpha) was high for the overall scale (0. 96); 2-wk
      reproducibility (intraclass correlation, ICC) was 0.82 (n = 38). Overall score
      was significantly correlated with FEV1 percentage of predicted (r = 0.20), and
      the Asthma Disease Severity Scale (r = -0.38). Correlations between overall score
      and the SF-36 Physical Component Summary (r = 0.49), SF-36 Mental Component
      Summary (r = 0.37), Cantril's Ladder (r = 0.23), and the Health Utilities Index
      (r = 0.22) supported the validity of the AQLQ in this sample. Comparison of
      reliability and validity estimates across racial groups found few substantive
      differences. Internal consistency, reproducibility, and validity estimates found
      in this sample were consistent with those of a reliable and valid measure and
      were comparable to those found in other populations. These results suggest the
      AQLQ is a useful indicator of health- related quality of life in low-income
      asthmatics.

PMID- 9769265
TI  - Infant and maternal outcomes in the pregnancies of asthmatic women.
AB  - We examined the relationship between infant and maternal outcomes and asthma
      complicating pregnancy, using historical cohort analysis of singleton live
      deliveries in New Jersey hospitals between 1989 and 1992 (n = 447,963). Subject
      mother-infant dyads were identified from linked birth certificate and maternal
      and newborn hospital claims data. Women with an International Classification of
      Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis code (493)
      for asthma (n = 2,289) were compared with a fourfold larger randomly selected
      control sample (n = 9,156) from the remaining pool of women. After controlling
      for the effects of important confounding variables, maternal asthma was
      associated with the following adverse infant outcomes: preterm infant (odds ratio
      [OR] = 1.36; 95% confidence interval [CI], 1.18 to 1.55), low birth weight (OR =
      1. 32; 95% CI, 1.10 to 1.58), small-for-gestational age (OR = 1.26; 95% CI, 1.10
      to 1.45), congenital anomalies (OR = 1.37; 95% CI, 1.12 to 1.68), and increased
      infant hospital length of stay (OR = 1.44; 95% CI, 1.25 to 1.65). The adverse
      maternal outcomes associated with maternal asthma were: pre-eclampsia (OR = 2.18;
      95% CI, 1.68 to 2. 83), placenta previa (OR = 1.71; 95% CI, 1.05 to 2.79),
      cesarean delivery (OR = 1.62; 95% CI, 1.46 to 1.80), and increased maternal
      hospital length of stay (OR = 1.86; 95% CI, 1.60 to 2.15). The results emphasize
      the need for maternal asthma to be added to the list of conditions that increase
      the risk of adverse pregnancy outcomes.

PMID- 9769266
TI  - Clinical utility of an amplification test based on ligase chain reaction in
      pulmonary tuberculosis.
AB  - We evaluated the sensitivity and specificity of a new semiautomated direct
      amplification test (DAT), the LCx-MTB, for the diagnosis of pulmonary
      tuberculosis (TB) and assessed its positive predictive value by focusing on
      patients with high clinical and radiologic suspicion of pulmonary TB. Respiratory
      tract specimens from 32 consecutive patients with high suspicion of active
      pulmonary TB (case patients) and from 204 control patients were cultured for
      Mycobacterium tuberculosis and tested by LCx-MTB. Sensitivity and specificity of
      LCx-MTB when compared with culture was, respectively, 80 and 98%. Pulmonary TB
      was confirmed in the 32 case patients without knowledge of the LCx results: 18
      patients were smear- and culture-positive for M. tuberculosis, and all gave at
      least one specimen that was LCx-positive. Eight patients were smear-negative
      culture-positive, and seven gave at least one LCx-positive specimen. LCx-MTB was
      negative in all the specimens obtained from six patients with smear- and culture
      negative TB. A positive LCx-MTB result in a smear negative specimen was 100%
      predictive that at least one of the case patients' specimens would yield M.
      tuberculosis. As a consequence, knowledge of the LCx-MTB results at the time of
      specimen collection could have hastened the start of the antituberculosis therapy
      in three (21%) smear-negative case patients and could have avoided unnecessary
      invasive diagnostic procedures in four (29%). We conclude that the sensitivity of
      LCx-MTB in detecting M. tuberculosis DNA in respiratory tract specimens is
      similar to other DATs, that LCx-MTB is a reliable test for confirmation of TB in
      smear-positive patients and that LCx-MTB could be beneficial as a diagnostic step
      in smear-negative patients with a high suspicion of pulmonary TB.

PMID- 9769267
TI  - Severe community-acquired pneumonia. Assessment of severity criteria.
AB  - The purpose of the study was to validate the criteria used in the guidelines of
      the American Thoracic Society (ATS) for severe community-acquired pneumonia
      (CAP). Severe pneumonia was defined as admission to the intensive care unit
      (ICU). Overall 331 nonsevere (84%) and 64 severe cases (16%) of CAP were
      prospectively studied. Mortality was 19 of 395 (5%) and 19 of 64 (30%),
      respectively. Single severity criteria as well as the ATS definition of severe
      pneumonia were assessed calculating the operative indices. A modified prediction
      rule including minor (baseline) and major (baseline or evolutionary) criteria was
      derived. Single minor criteria at admission had a low sensitivity and positive
      predictive value. Defining severe pneumonia according to the ATS guidelines had a
      high sensitivity (98%). However, specificity and positive predictive value were
      low (32% and 24%, respectively). A modified prediction rule (presence of two or
      three minor criteria [systolic blood pressure < 90 mm Hg, multilobar involvement,
      PaO2/FIO2 < 250] or one of two major criteria [requirement of mechanical
      ventilation, presence of septic shock]) had a sensitivity of 78%, a specificity
      of 94%, a positive predictive value of 75%, and a negative predictive value of
      95%. The ATS definition of severe pneumonia was highly sensitive but
      insufficiently specific and had a low positive predictive value. Our suggested
      modified rule had a more balanced performance and, if validated in an independent
      population, may represent a more accurate definition of severe CAP.

PMID- 9769268
TI  - L-2-Oxothiazolidine-4-carboxylic acid prevents endotoxin-induced cardiac
      dysfunction.
AB  - We tested the hypothesis that treatment with the glutathione repleting agent, L-2
      oxothiazolidine-4-carboxylic acid (OTZ), could prevent endotoxin-induced
      ventricular dysfunction. Rabbits were treated with OTZ 2.4 g/kg (10% solution
      subcutaneously), or an equal volume and osmolality of saline, 24 h prior to, and
      again (intravenously) just prior to, infusion of 1 mg/kg E. coli endotoxin (or
      vehicle control). Ventricular contractility was measured in isolated hearts
      perfused by support rabbits. Contractility did not change in control groups
      (Saline/Control [n = 7] or OTZ/Control [n = 7]) over 6 h. However, Emax decreased
      in the Saline/Endotoxin group (-16.1 +/- 4.5% from baseline, n = 7, p < 0.05) and
      this was prevented by pretreatment with OTZ in the OTZ/ Endotoxin group (+6.3 +/-
      4.1%, n = 7, p < 0.05 by analysis of variance). To better understand the
      mechanism of this effect we measured myocardial glutathione concentration and
      found it to be greater in OTZ/Endotoxin animals (104 +/- 4 ng/g) than in the
      Saline/Endotoxin animals (80 +/- 3 ng/g, p < 0.05). OTZ did not appreciably alter
      the endotoxin-induced increase in serum concentration of tumor necrosis factor
      (TNF) or the endotoxin-induced increase in myocardial leukocyte content. We
      conclude that oxygen radicals contribute to the early decrease in left
      ventricular contractility after endotoxin infusion and this decrease may be
      prevented by OTZ.

PMID- 9769269
TI  - Ventilation above closing volume reduces pulmonary vascular resistance
      hysteresis.
AB  - The aim of this study was to determine the relationship of pulmonary vascular
      resistance (PVR) hysteresis and lung volume, with special attention to the
      effects of ventilation around closing volume (CV). Isolated, blood-perfused
      canine left lower lung lobes (LLL) were incrementally inflated and deflated.
      Airway and pulmonary artery pressures (PAP) were recorded after each stepwise
      volume change. Constant blood flow was provided (600 ml/min) and the pulmonary
      vein pressure (PVP) was held constant at 5 cm H2O. PAP changes, therefore, were a
      direct index of PVR changes. Group 1 lobes underwent a full inflation from
      complete collapse to total lobe capacity (TLC) followed by a full deflation.
      Group 2 lobes underwent two deflation/inflation cycles, after an initial full
      inflation. These cycles, both beginning at TLC, had deflation end above and below
      CV, respectively. Significant PVR hysteresis was noted when the first inflation
      and deflation were compared. The maximum difference in PAP on deflation was 3.3
      cm H2O or 11%. The mean decrease was 2.7 cm H2O for 18 lobes (p < 0.0001). The
      PAPs on all subsequent inflations or deflations that began above CV remained 9%
      lower than the initial inflation (n = 9, p < 0.0001), but were not different from
      each other. However, the final inflation which began from below CV resulted in a
      30% return of PVR hysteresis (mean increase in PAP of 0.8 cm H2O, n = 7, p <
      0.004). We conclude that there is hysteresis in the PVR response during
      ventilation, with decreased PVR during deflation relative to the initial
      inflation, that this hysteresis is absent when lung volume is maintained greater
      than CV, and that hysteresis returns when inflation occurs after deflation below
      CV.

PMID- 9769270
TI  - Responsiveness to mannitol in asthmatic subjects with exercise- and
      hyperventilation-induced asthma.
AB  - We investigated airway responsiveness to mannitol, a new hyperosmolar challenge,
      in persons hyperresponsive to airway drying. We studied 36 asthmatic subjects, 18
      to 40 yr of age, responsive to exercise (n = 23) and eucapnic hyperventilation (n
      = 28) defined by a 10% fall in FEV1. Fifteen subjects performed both challenges.
      All subjects performed a challenge with dry powder mannitol, encapsulated and
      delivered via a Dinkihaler until a 15% decrease in FEV1 was documented or a
      cumulative dose of 635 mg was delivered. All subjects responsive to eucapnic
      hyperventilation and all but one subject responsive to exercise were responsive
      to mannitol. Sixty-nine percent of subjects had a positive response to mannitol
      after less than 155 mg (6 capsules) and 94% less than 320 mg (10 capsules). The
      provoking dose of mannitol required to cause a 15% fall in FEV1 (PD15) was
      related to the severity of the response to exercise (Pearson's correlation
      coefficient [rp] = 0.68, p < 0.01) and eucapnic hyperventilation (rp = 0.68, p <
      0.01) in subjects who were not taking inhaled corticosteroids. The mean (+/- SD)
      maximum percent fall in FEV1 after mannitol was 24.4 +/- 6.2% and recovery to
      bronchodilator occurred within 10 min in most subjects. The mannitol test is
      simple, inexpensive, faster to perform than hyperpnea with dry air and could
      become an office-based test. Further studies are now required to determine the
      sensitivity of mannitol to identify exercise-induced asthma in a random
      population.

PMID- 9769271
TI  - Involvement of alpha-4 integrins in allergic airway responses and mast cell
      degranulation in vivo.
AB  - Antibodies against integrins have been shown to inhibit allergic airway
      responses. The purpose of this study was to test the hypothesis that the beta1
      integrin, very late antigen-4 (VLA-4), is involved in mast cell activation
      triggered by allergen exposure in sensitized animals. To do this we studied Brown
      Norway rats that were sensitized to ovalbumin (OA; 1 mg subcutaneously) using
      Bordetella pertussis as an adjuvant. Two weeks later rats were challenged with
      OA, pulmonary resistance (RL) was determined, and the concentrations of histamine
      and tryptase in bronchoalveolar lavage fluid and N-acetyl-leukotriene (LT)E4 in
      bile were measured. Pretreatment with a monoclonal antibody against VLA-4 (TA-2)
      attenuated the early response after OA challenge (342.9 +/- 24.4% baseline RL
      versus 153.3 +/- 19.4%; p < 0.01). There were significantly lower concentrations
      of histamine (67.11 +/- 11.90 microgram/ml versus 26.69 +/- 1.84; p < 0.01) and
      tryptase (0.143 +/- 0. 035 microgram/ml versus 0.053 +/- 0.022 microgram/ml; p <
      0.01) in TA-2-treated animals. The increases in the concentrations of biliary N
      acetyl-LTE4 after OA challenge were also significantly lower in TA-2-treated
      animals. These data suggest that a selective anti-VLA-4 monoclonal antibody
      prevents early responses through inhibition of mast cell activation.

PMID- 9769272
TI  - Impaired perception of dyspnea in patients with severe asthma. Relation to sputum
      eosinophils.
AB  - Poor dyspnea perception might be a risk factor for developing asthma
      exacerbations. We investigated whether severe asthmatics with recurrent
      exacerbations (brittle asthma) have different dyspnea perception and sputum cells
      compared with equally severe, but stable asthmatics, or patients with mild
      steroid-naive asthma. Fifteen brittle asthmatics (13 female, median age 28 yr
      [range, 20 to 47 yr]), 15 matched severe-stable asthmatics (14 female, median age
      26 yr [range, 17 to 52 yr]), and 11 mild asthmatics (8 female, median age 25 yr
      [range, 19 to 43 yr]) underwent inhalation tests with methacholine (MCh), and
      hypertonic saline combined with sputum induction. Dyspnea was assessed by Borg
      and Visual Analogue Scale (VAS), plotted against the percent fall in FEV1, and
      expressed as the slope of the regression line (Slope-Borg and Slope-VAS). The
      brittle and stable asthmatics had poorer perception than patients with mild
      asthma (Slope-Borg [p = 0.036], Slope-VAS [p < 0.001] for MCh). In patients with
      brittle asthma the perception was less as compared with severe-stable asthma
      (Slope-Borg for MCh: p = 0.05). In the severe asthmatics there was an inverse
      correlation between sputum eosinophilia and Slope-Borg and Slope-VAS (R = -0.55,
      p = 0. 002 and R = -0.37, p = 0.049), whereas this correlation was a positive one
      in the mild asthmatics (R = 0.79, p = 0.012 and R = 0. 67, p = 0.05). In
      conclusion, patients with severe asthma, particularly those with recurrent
      exacerbations, have blunted perception of dyspnea, which is related to the degree
      of sputum eosinophilia. This suggests that increased sputum eosinophilia is an
      indicator of clinical instabililty, and that eosinophilic airways inflammation
      might affect dyspnea perception in severe asthma.

PMID- 9769273
TI  - Instability of ventilatory control in patients with obstructive sleep apnea.
AB  - Because of the oscillatory pattern of upper airway resistance and breathing
      during sleep in patients with obstructive sleep apnea (OSA), we hypothesized that
      OSA patients have an underlying instability of ventilatory drive to inspiratory
      muscles. To assess the stability of ventilatory drive in OSA patients and
      controls, we used the pseudorandom binary stimulation (PRBS) test and examined
      the closed- and open-loop responses to hyperoxic hypercapnia. The closed-loop
      response is produced by interactions of dynamic gain in controller, plant, and
      ventilatory feedback. The open-loop response reflects controller dynamic gain or
      frequency-dependent chemosensitivity. As compared with 16 nonapneic, nonobese
      control subjects, a group of nine obese OSA patients had a higher peak response
      and a more rapid and irregular recovery phase of the closed-loop CO2 response in
      the PRBS test. The two groups had similar open-loop responses in the PRBS test,
      suggesting that central dynamic CO2 chemosensitivity was not abnormal in OSA. We
      conclude that the differences between OSA patients and controls in the closed
      loop response in the PRBS test are not due to differences in dynamic controller
      gain, but are related to differences in dynamic plant gain and/or negative
      ventilatory feedback. In addition to OSA, obesity may affect these variables and
      may have been responsible for our findings.

PMID- 9769274
TI  - Polymerase chain reaction to detect Mycobacterium tuberculosis in histologic
      specimens.
AB  - There is a need for rapid and sensitive detection of Mycobacterium tuberculosis
      in tissue specimens. A polymerase chain reaction (PCR)-based assay for the
      diagnosis of tuberculosis was evaluated in 60 formalin-fixed tissue specimens,
      the target for the amplification being a segment of IS6110 in the M. tuberculosis
      chromosome. Of the 60 formalin-fixed, paraffin-embedded tissue specimens studied,
      57 showed granulomatous inflammation and 53 had been cultured for mycobacteria;
      10 were positive for M. tuberculosis and three were positive for other
      mycobacteria. Of 60 samples, 15 showed acid-fast bacilli on special staining.
      When done comparatively on a positive culture for M. tuberculosis, PCR for M.
      tuberculosis DNA in 60 tissue samples was 100% sensitive and 93% specific, having
      a positive predictive value of 76.9% and negative predictive value of 100%. PCR
      for M. tuberculosis DNA done on tissue samples was positive for 14 of 19 patients
      who had a clinical diagnosis of tuberculosis, negative for all six patients with
      nontuberculous mycobacterial infections, and negative for all 33 patients who had
      a diagnosis of a disease other than mycobacterial infection. When compared with
      the clinical diagnosis of tuberculosis, PCR for M. tuberculosis DNA in these
      patients' tissues was 73.6% sensitive and 100% specific, having a positive
      predictive value of 100% and negative predictive value of 88.6%. These data
      indicate that PCR amplification is useful for detecting M. tuberculosis DNA in
      formalin-fixed tissue specimens, and that it can be used to increase diagnostic
      accuracy in patients who have perplexing diagnostic problems associated with a
      granulomatous tissue response.

PMID- 9769275
TI  - Effects of aerosolized interferon-alpha in patients with pulmonary tuberculosis.
AB  - Interferon-alpha (IFN-alpha) is a cytokine exerting pleiotropic activities,
      including antimicrobial effects, especially directed against intracellular
      infectious bacteria. It may be administered by aerosol to reach the lower
      respiratory tract without systemic side effects. The aim of the study reported
      here was the evaluation of aerosolized IFN-alpha treatment (3 MU/dose, given
      three times a week; total study dose: 72 MU/2 mo) in combination with
      conventional antimycobacterial therapy in patients with pulmonary tuberculosis.
      Two groups of 10 patients each were compared before and after 2 mo of
      conventional antituberculous chemotherapy with or without inhaled IFN-alpha.
      Several biologic (bronchoalveolar lavage fluid [BALF] cellularity, Mycobacterium
      tuberculosis [MT] number in sputum), biochemical (BALF concentrations of 10
      cytokines, BALF IFN-alpha receptor levels), and clinical (fever, vital signs,
      high-resolution computed tomography [HRCT] images) measures were made in these
      patients at the time of their enrollment and at the end of the observation period
      of the study. Fever, MT number in sputum, and abnormalities in HRCT images showed
      significantly earlier resolution in the IFN-alpha-treated group, together with a
      more significant decrease in BALF interleukin-1beta (IL-1beta), IL-6, and tumor
      necrosis factor-alpha (TNF-alpha) concentrations and significantly greater pre-
      versus posttreatment variations in IL-2 and IFN-gamma. These data, taken
      together, suggest that IFN-alpha administration may favorably affect the
      evolution of pulmonary tuberculosis when combined with antimycobacterial therapy.

PMID- 9769276
TI  - A national survey of end-of-life care for critically ill patients.
AB  - In some intensive care units (ICUs), fewer patients who die now undergo attempts
      at cardiopulmonary resuscitation (CPR), and many more have life support actively
      withdrawn prior to death than did a decade ago. To determine the frequency of
      withdrawal of life support, we contacted every American postgraduate training
      program with significant clinical exposure to critical care medicine, asking them
      prospectively to classify patients who died into one of five mutually exclusive
      categories. We received data from 131 ICUs at 110 institutions in 38 states.
      There were 6,303 deaths, of which 393 patients were brain dead. Of the remaining
      5,910 patients who died, 1,544 (23%) received full ICU care including failed
      cardiopulmonary resuscitation (CPR); 1,430 (22%) received full ICU care without
      CPR; 797 (10%) had life support withheld; and 2,139 (38%) had life support
      withdrawn. There was wide variation in practice among ICUs, with ranges of 4 to
      79%, 0 to 83%, 0 to 67%, and 0 to 79% in these four categories, respectively.
      Variation was not related to ICU type, hospital type, number of admissions, or
      ICU mortality. We conclude that limitation of life support prior to death is the
      predominant practice in American ICUs associated with critical care training
      programs. There is wide variation in end-of-life care, and efforts are needed to
      understand practice patterns and to establish standards of care for patients
      dying in ICUs.

PMID- 9769278
TI  - Risk factors for pulmonary tuberculosis in bone marrow transplant recipients.
AB  - Little is known about the profile of infection with Mycobacterium tuberculosis in
      bone marrow transplant (BMT) recipients. Of five BMT series with a total of more
      than 5,000 patients, only 10 cases of M. tuberculosis infection were described,
      with an overall incidence of 0.19%. We have conducted a prospective evaluation of
      183 consecutive BMT recipients, and 10 patients were found to develop pulmonary
      tuberculosis post-BMT, yielding an incidence of 5.5%. We described the clinical
      features of these 10 patients, and analyzed the risk factors for development of
      tuberculosis using age- and sex-matched case control subjects who did not develop
      the disease. The median age of the 10 patients who developed tuberculosis was 29
      yr (range, 17 to 40 yr). The median time for onset of symptoms was 150 d (range,
      23 to 550 d), mainly presenting with fever and cough, with infiltrates on chest
      radiograph. Respiratory tract specimens, mostly sputum, yielded positive smears
      for acid-fast bacilli in three and positive M. tuberculosis culture in eight,
      whereas lung tissue histology was the first diagnostic test in two patients.
      Treatment with standard antituberculosis drugs for a longer duration was highly
      effective, with no excessive side effects. Risk factors identified for
      development of tuberculosis included allogeneic BMT (p < 0.05, relative risk [RR]
      = 23.7), total body irradiation (p < 0. 05, RR = 4.9), and chronic graft-versus
      host disease (GVHD) (p < 0. 05, RR = 3.6). It is postulated that chronic GVHD
      predisposed to development of tuberculosis mainly via disruption of host
      reconstitution of immune defenses against M. tuberculosis.

PMID- 9769277
TI  - Salmeterol prevents aspirin-induced attacks of asthma and interferes with
      eicosanoid metabolism.
AB  - We determined the effect of a long acting beta2-agonist, salmeterol, on aspirin
      induced asthma (AIA) attacks and urinary release of eicosanoids in a double
      blind, placebo-controlled, crossover study in 10 asthmatics sensitive to aspirin.
      The patients inhaled 50 microgram of salmeterol or placebo 15 min prior to a
      cumulative challenge with increasing doses of lysine-aspirin (L-ASA) (Part I),
      and before a single, predetermined dose of L-ASA that caused a 20% fall in FEV1
      (PD20) (Part II). Salmeterol significantly attenuated aspirin-precipitated
      bronchoconstriction and the increase in urinary LTE4. Salmeterol also prevented
      the decrease in blood eosinophils, and abolished the correlation between the
      urinary levels of LTE4 and provocative doses of aspirin. In addition, PGD-M, the
      major urinary metabolite of PGD2, increased after L-ASA inhalation in six of nine
      subjects; this increase was blocked in all six by salmeterol. The protective
      effect of salmeterol on aspirin-induced attacks and mediator release suggests
      that it may be efficacious in aspirin-sensitive asthma.

PMID- 9769279
TI  - Asthma and natural colds. Inflammatory indices in induced sputum: a feasibility
      study.
AB  - We examined the feasibility of using induced sputum to evaluate the airway
      inflammatory response to natural acute respiratory virus infections. We recruited
      eight asthmatics and nine healthy subjects on Day 4 of a cold. Viral infection
      was confirmed in six of the asthmatics (influenza A or B) and six of the healthy
      subjects (influenza A, rhinovirus, adenovirus, respiratory syncytial virus, and
      coronavirus). In the subjects with confirmed virus infection, five of the
      asthmatics had an objective exacerbation of asthma during the cold. Their sputum
      on Day 4 showed a high median total cell count of 19.7 x 10(6) cells/ml with a
      modest neutrophilia (58. 5%) and high levels of interleukin-8 (IL-8) (16,000
      pg/ml), eosinophilic cationic protein (ECP) (1,880 microgram/L) and very high
      levels of fibrinogen (250 mg/L). In contrast, the proportion (1.3%) and absolute
      number of eosinophils was low. IL-2 levels were within the normal range, whereas
      IL-5 and interferon gamma were under the limit of detection of the assays. In the
      healthy subjects with a confirmed virus infection the sputum findings were
      qualitatively similar but significantly less prominent. Sputum IL-8 on Day 4 was
      strongly correlated with neutrophils (rs = 0.8, p < 0.001). This correlation was
      also significant when each group was analyzed separately. On Day 21 there was a
      fall in the absolute number of neutrophils and in ECP and fibrinogen levels in
      both groups. Similar results were found in the two asthmatic and three healthy
      subjects with a cold of comparable severity but in whom viral infection was not
      confirmed. We conclude that induced sputum examination can be used to study the
      effects of natural colds and influenza on the airways of the lungs. The results
      also suggest that natural colds, on Day 4, cause neutrophilic lower airway
      inflammation that is greater in asthmatics than in healthy subjects. The greater
      inflammatory response in asthmatics may be due to the changes associated with
      trivial eosinophilia or to the different viruses involved.

PMID- 9769280
TI  - Analysis of clinical methods used to evaluate dyspnea in patients with chronic
      obstructive pulmonary disease.
AB  - When dyspnea must be assessed clinically, there are three methods of assessment:
      the measurement of dyspnea with activities of daily living using clinical dyspnea
      ratings such as the modified Medical Research Council (MRC), the Baseline Dyspnea
      Index (BDI), and the Oxygen Cost Diagram (OCD); the measurement of dyspnea during
      exercise using the Borg scale; to assess the influence of dyspnea on health
      related quality of life (HRQoL) using disease-specific questionnaires such as the
      St. George's Respiratory Questionnaire (SGRQ) and the Chronic Respiratory Disease
      Questionnaire (CRQ). The purpose of the present cross-sectional study was to
      clarify relationships between dyspnea ratings and HRQoL questionnaires by
      applying factor analysis. One hundred sixty-one patients with mild to severe COPD
      completed pulmonary function tests, progressive cycle ergometer testing for
      exercise capacity, assessment of dyspnea, HRQoL, anxiety, and depression. Factor
      analysis demonstrated that the MRC, BDI, OCD, and Activity of the SGRQ, and
      Dyspnea of the CRQ, were grouped into the same factor, and the frequency
      distribution histograms of these five measures showed virtually the same
      distribution. The Borg scale at the end of maximum exercise was found to be a
      different factor. The MRC, BDI, OCD, and Activity in the SGRQ, and Dyspnea in the
      CRQ demonstrated the same pattern of correlation with physiologic data, and they
      had significant relationships with FEV1 (correlation coefficients [Rs] = 0.31 to
      0. 48) and maximal oxygen uptake (Rs = 0.46 to 0.60). Disease-specific HRQoL
      questionnaires, the SGRQ and the CRQ, which contain a specific dimension for
      evaluating dyspnea, may be substituted for clinical dyspnea ratings in a cross
      sectional assessment. Dyspnea rating at the end of exercise may provide further
      information regarding dyspnea.

PMID- 9769281
TI  - The effects of learning on the ventilatory responses to inspiratory threshold
      loading.
AB  - Progressive threshold loading (PTL) is frequently used to assess inspiratory
      muscle endurance in health and disease. We and others have noted a systematic
      increase in endurance with the first few exposures to the task in subjects
      previously naive to PTL, which may not be related to conditioning of the muscles
      themselves. The purpose of this study was to investigate the mechanisms
      responsible for this increased endurance by examining the ventilatory responses
      to 3 PTL tests, each > 24 h apart, in 18 healthy subjects. During PTL, threshold
      pressure (Pth) was increased by approximately 10% every 2 min until task failure.
      Subjects were allowed to adopt any breathing pattern. Respiratory muscle strength
      (maximal inspiratory pressure [PImax]) was unchanged over successive tests while
      maximal Pth (Pthmax) during PTL increased (69 +/- 17, 77 +/- 16, and 86 +/- 11%
      of PImax, respectively, p < 0.05) (mean +/- SD), indicating that the increased
      Pthmax could not be attributed to improved respiratory muscle strength. Breathing
      pattern changed with successive tests, so that for comparative loads inspiratory
      time (TI), respiratory frequency (f ), and duty cycle (TI/Ttot) decreased. This
      change in breathing pattern did not alter respiratory muscle efficiency
      (respiratory muscle V O2/work), which was similar in each test (2.4 +/- 2.2%),
      but perceived effort (Borg Score), which was maximal at task failure in each
      test, decreased at comparative loads with successive tests. Thus, Pthmax during
      initial tests appeared to be limited by discomfort rather than respiratory muscle
      function. These findings suggest that the increased Pthmax with successive tests
      is a consequence of differences in the breathing pattern adopted, reflecting
      neuropsychological rather than respiratory muscle conditioning. Measurements from
      PTL should only be used to assess respiratory muscle performance after allowing
      time for learning.

PMID- 9769282
TI  - Association between diet and lung cancer location.
AB  - Lung cancers occur more commonly in the upper lobes than in the lower lobes, but
      its pathophysiologic basis is not well understood. Because numerous studies have
      reported a consistent inverse relationship between lung cancer risk and intake of
      certain vegetables and fruits, we hypothesized that the balance between diet
      derived protective substances delivered via the circulation and cigarette-derived
      carcinogenic substances delivered via the airways would be less favorable in the
      upper lobes compared with the lower lobes, hence accounting for the upper lobe
      predominance of tumors among smokers. Thus, we examined the association between
      diet and tumor location in 328 patients with lung cancer. The ratio of upper to
      lower lobe tumors was 2.5:1.0. In univariate analysis, age, height, weight, sex,
      race, family history of cancer, education level, tumor histology, calories
      consumed per day, and intake of animal fat did not differ significantly between
      patients with upper versus lower lobe tumors. Predictors of tumor location in
      univariate analysis were family history of lung cancer; smoking history; history
      of asbestos exposure; and intakes of yellow-orange vegetables, alpha-carotene,
      beta-carotene, and vitamins A, C, and E. In multivariable logistic regression
      analysis, the independent predictors of upper lobe tumor location were family
      history of lung cancer (p = 0.03), history of asbestos exposure (p = 0.02), less
      intake of yellow-orange vegetables (p < 0.04), and less intake of vitamin E (p =
      0.05). Our results show a strong inverse association between upper lobe location
      of lung cancer and intake of yellow-orange vegetables and vitamin E.

PMID- 9769283
TI  - Filtration of diaspirin crosslinked hemoglobin into lung and soft tissue lymph.
AB  - Diaspirin crosslinked hemoglobin (DCHb) is a new blood substitute manufactured
      from human blood. To evaluate its microvascular filtration properties, we infused
      DCLHb into unanesthetized sheep (10%, 20 ml/kg) and measured the flow and
      composition of lung and soft tissue lymph. For comparison, we also infused human
      serum albumin (HSA; 10%, 20 ml/kg). DCLHb raised systemic and pulmonary arterial
      pressures from baseline values of 83 +/- 7 and 13 +/- 2 mm Hg, respectively, to
      peak values of 113 +/- 9 and 26 +/- 3 mm Hg (p < 0.05 versus baseline). These
      increases were significantly greater than those associated with HSA, which raised
      systemic and pulmonary arterial pressures from baseline values of 86 +/- 4 and 13
      +/- 2 mm Hg, respectively, to peak values of 97 +/- 3 and 21 +/- 7 mm Hg (p <=
      0.05 versus baseline and versus DCLHb). These differences reflect the known
      pressor properties of DCLHb. Accordingly, DCLHb raised lung and soft tissue lymph
      flows to peak values of 12.2 +/- 3.8 and 1.6 +/- 0.7 ml/30 min, respectively,
      while HSA raised lung and soft tissue lymph flows to peak values of 7.5 +/- 4.8
      and 4.6 +/- 1.9 ml/30 min, respectively (p <= 0.05 versus DCLHb). The half-times
      of DCLHb equilibration from plasma into lung and soft tissue lymph of 1. 0 +/-
      0.3 and 2.1 +/- 1.1 h, respectively, were significantly faster than HSA
      equilibration half-times of 3.1 +/- 0.2 and 3.8 +/- 0.9 h. Filtration differences
      between DCLHb and HSA appear to be due to the pressor properties DCLHb.

PMID- 9769284
TI  - Relation between alpha, beta, and gamma human amiloride- sensitive epithelial Na+
      channel mRNA levels and nasal epithelial potential difference in healthy men.
AB  - To analyze messenger RNA (mRNA) levels for the alpha, beta, and gamma subunits of
      the human amiloride-sensitive epithelial Na+ channel (hENaC) in respiratory
      epithelia, we developed a competitive quantitative reverse transcriptase
      polymerase chain reaction (QRT-PCR) assay specific for each subunit, using two
      human respiratory epithelial-cell lines. We next determined the relation between
      hENaC mRNA levels and the biologic activity of the hENaC in the respiratory
      epithelium of eight normal men. The electrical potential difference (PD) between
      the epithelium of the inferior nasal turbinate and the subcutaneous space was
      measured, using control and amiloride (100 microM) solutions. QRT-PCR measurement
      of hENaC-subunit mRNAs and epithelial-specific cytokeratin 18 mRNA allowed us to
      normalize hENaC expression to epithelial-cell RNA. Respective values for alpha,
      beta, and gamma hENaC mRNA levels in epithelium obtained at the site of maximal
      PD were 39 +/- 4.0, 7.5 +/- 0.92, and 1.8 +/- 0.25 attomol/fmol cytokeratin mRNA,
      respectively. Respiratory epithelial PD exhibited a significant negative
      correlation with gamma hENaC (r2 = 0.72, p < 0.01), tended to increase with
      increasing alpha hENaC, and was unaffected by beta hENaC mRNA levels. Our results
      suggest that hENaC activity in vivo is influenced by expression of the gene for
      gamma hENaC. The assay used in the study provides a useful tool for evaluating
      Na+-channel expression in clinically relevant patient populations.

PMID- 9769285
TI  - AIDS-related primary pulmonary lymphoma.
AB  - We describe 12 cases of AIDS-related primary pulmonary lymphoma occurring between
      1986 and 1996 in a large French cohort of HIV-infected patients. Diagnostic
      criteria were: (1) histologically proven lymphomatous pulmonary involvement; (2)
      absence of mediastinal and/or hilar adenopathy on chest radiography; (3) absence
      of extrathoracic lymphoma extension. All patients were severely immunodeficient
      at the time of diagnosis. All but one patient presented with B and/or nonspecific
      respiratory symptoms. Chest radiography showed one or more marginated nodule(s)
      or large mass. CT scan showed a cavitary lesion in five patients. No lymph node
      enlargement or specific pleural effusion was detected. Transthoracic needle
      biopsies were performed in 10 patients and avoided open-lung biopsy for the
      diagnosis of lymphoma in five patients. All but one of the primary pulmonary
      lymphoma were high-grade B-cell non-Hodgkin's lymphomas. Using antilatent
      membrane protein-1 antibodies and an Epstein-Barr-Virus-encoded RNA transcript
      specific probe, latent EBV infection of tumor cells was demonstrated in every
      case. All but one of the patients received chemotherapy. The median survival time
      was 4 mo, and no patient was still alive at the cut-off date for this analysis.
      Progessive pulmonary lymphoma was the main cause of death, but infections were
      also frequent.

PMID- 9769286
TI  - Airspace configuration at different transpulmonary pressures in normal and
      paraquat-induced lung injury in rats.
AB  - The aim of this study is to evaluate histoarchitecture of airspaces at different
      positive transpulmonary pressures, both during inflation and deflation of excised
      normal and paraquat-damaged rat lungs. Freshly excised lungs were placed in a
      plethysmograph connected to a graded pipette. Immediately after the achievement
      of the desired pressure level (5, 15, 25 cm H2O during inflation, and 15 and 5 cm
      H2O during deflation), the tracheal cannula was occluded and lungs were quick
      frozen by immersion in liquid nitrogen, and fixed using Carnoy's solution.
      Sections representing the central and peripheral areas of the lungs were sampled
      and processed for paraffin embedding and stained with hematoxylin-eosin. By means
      of stereological techniques, surface-to-volume ratio (S/V) and the fraction of
      large-volume gas-exchanging airspaces (LVGEAS) were determined. We observed in
      paraquat-treated animals evidence of alveolar instability close to the resting
      volume. Structural unevenness was minimized by massive recruitment followed by
      alveolar pressurization. In conclusion, this work demonstrates that morphological
      evidence of uneven distribution of inspired air may be partially reversed by
      applying larger alveolar pressures. These larger pressures applied at the end
      expiration in vivo (positive end-expiratory pressure, PEEP) can minimize the
      distortion of lung microarchitecture during ventilation.

PMID- 9769287
TI  - Polyclonal Mycobacterium avium complex infections in patients with nodular
      bronchiectasis.
AB  - Mycobacterium avium complex (MAC) isolates among patients with chronic lung
      disease were studied for their heterogeneity using genetic identification
      methods, pulsed field gel electrophoresis (PFGE) and seroagglutination. A mean of
      7.3 cultures per patient were collected from 17 patients with nodular
      bronchiectasis who were elderly (mean age 66 yr), predominantly female (76%), had
      smoked a mean of only 5 pack-years, and had multifocal bronchiectasis. A mean of
      7.7 cultures per patient were collected from nine patients with upper lobe
      cavitary disease who were younger (mean age 52 yr), predominantly male (78%), and
      heavy smokers (mean 56 pack-yr). A mean of 2.9 PFGE types (genotypes) per patient
      (range, 1 to 9) were identified in the nodular bronchiectasis group, with 15 of
      17 patients (88%) having two or more genotypes and 9 of 17 (53%) having three or
      more genotypes. In contrast a mean of 1.2 genotypes were identified in the
      patients with cavitary disease, with only 1 of 9 (11%) having two or more
      genotypes. Mycobacterium intracellulare was the most frequently recovered
      genotype in both groups and most isolates were rough or nontypable by
      seroagglutination. Some genotypes from the same patient considered different by
      current PFGE criteria had the same serotype and shared 11 to 20 common PFGE
      bands, suggesting they were related. These data demonstrate that patients with
      nodular bronchiectasis have multiple and/or repeated infections due to MAC
      whereas patients with upper lobe cavitary disease are usually infected with only
      a single strain.

PMID- 9769288
TI  - Airway structure and function in Eisenmenger's syndrome.
AB  - The responsiveness of airways from patients with Eisenmenger's syndrome (n = 5)
      was compared with that in airways from organ donors (n = 10). Enhanced
      contractile responses to cholinergic stimulation were found in airways from
      patients with Eisenmenger's syndrome. The maximal responses to acetylcholine,
      carbachol, and parasympathetic nerve stimulation in airway tissue from these
      patients were 221%, 139%, and 152%, respectively, of the maximal responses
      obtained in donor tissue. Further, relaxation responses to isoproterenol and
      levocromakalim were absent (n = 2) or markedly impaired (n = 3) in airways from
      patients with Eisenmenger's syndrome. This attenuated relaxation response was
      nonspecific in that it was also absent after vasoactive intestinal peptide,
      sodium nitroprusside, papaverine, and electrical field application. These
      observations can most likely be explained by a decrease in intrinsic smooth
      muscle tone, as precontraction of airways revealed relaxation responses that were
      equivalent to those obtained in donor tissues. Morphometric analysis of tissues
      used for the functional studies revealed no differences in the airway dimensions
      (internal perimeter) or airway wall components (e.g., smooth muscle, cartilage)
      or total area to explain these observations. Although the mechanism for this
      observed decrease in intrinsic airway smooth muscle tone is not certain, it may
      be due to alteration in the substructure of the airway wall or, alternatively,
      may result from the continued release of depressant factors in the vicinity of
      the smooth muscle which permanently alters smooth muscle responsiveness.

PMID- 9769290
TI  - State-related changes in upper airway caliber and surrounding soft-tissue
      structures in normal subjects.
AB  - State-dependent changes in upper airway caliber were studied with magnetic
      resonance imaging (MRI) techniques. We hypothesized that changes in airway
      caliber during sleep in normal subjects would result from positional and
      dimensional changes in upper airway soft-tissue structures, including the lateral
      pharyngeal walls, tongue, and soft palate. We used MRI to study 15 normal
      subjects during wakefulness and sleep. Sleep was facilitated by one night of
      sleep deprivation prior to MRI. During sleep, the volume of the retropalatal (RP)
      airway was reduced by 19% (p = 0.03). The volume of the retroglossal (RG) airway
      was not significantly reduced during sleep, suggesting that the RP region may be
      more likely to collapse. The mean minimal cross-sectional airway area was reduced
      by 228% (p = 0.004) in the RP and by 22% (p = 0.02) in the RG region during sleep
      as compared with values in anatomically matched axial images during wakefulness.
      Airway anteroposterior (AP) and lateral dimensions were also significantly
      reduced in the RP region. Airway narrowing in the RP region was associated with a
      7% increase in thickness of the lateral pharyngeal walls (p = 0.04). In nine
      subjects, sagittal data showed significant posterior displacement of the soft
      palate during sleep as compared with wakefulness. Multiple linear regression
      analyses indicated that reduction in the RP airway area during sleep resulted
      from posterior movement of the soft palate, thickening of the lateral pharyngeal
      walls, and an increase in tongue oblique distance. We conclude that the lateral
      pharyngeal walls play an important role in upper airway narrowing during sleep in
      normal subjects.

PMID- 9769289
TI  - Goblet cell degranulation after antigen challenge in sensitized guinea pigs. Role
      of neutrophils.
AB  - Mucus hypersecretion is a common characteristic of asthma. Acute severe asthma is
      often associated with neutrophilic infiltration into airways. Neutrophils contain
      elastase, a potent secretagogue in airways. Therefore, we hypothesized that
      instillation of ovalbumin in sensitized guinea pigs causes goblet cell secretion
      by releasing elastase from recruited neutrophils. When we instilled ovalbumin
      into the trachea of ovalbumin-sensitized guinea pigs, early recruitment of
      neutrophils identified by 3,3'- diaminobenzidine staining, and goblet cell
      degranulation measured with a semiautomatic computer-based imaging system
      occurred. The Leumedin NPC 15669 (a drug that inhibits leukocyte recruitment) and
      an antibody to intercellular adhesion molecule-1 (ICAM-1) both prevented
      neutrophil recruitment and goblet cell degranulation, implicating leukocytes in
      the response. Using immunofluorescence we showed that the leukocytes recruited
      early after antigen challenge were CD-16-positive, implicating neutrophils.
      Pretreatment with the selective neutrophil elastase inhibitor ICI 200,355 also
      prevented ovalbumin-induced goblet cell degranulation, implicating elastase. We
      conclude that ovalbumin-induced goblet cell degranulation is due to neutrophil
      recruitment and elastase release.

PMID- 9769291
TI  - Inspiratory muscle function and body composition in cystic fibrosis.
AB  - Loss of body mass, which occurs in the later stages of cystic fibrosis (CF),
      probably affects all body compartments. We hypothesized that loss of skeletal
      muscle mass would include inspiratory muscles and impair their function. To test
      this, we determined the effect of body mass index (BMI) and lean body mass (LBM)
      depletion on handgrip (HG) force and inspiratory muscle function (IMF). The
      maximum inspiratory pressure (MIP) and the sustained maximum inspiratory pressure
      (SMIP) were measured with a computerized system. The relationship of IMF and
      reduced BMI to survival was studied in 49 patients, and a further 25 patients
      were studied to define the link between IMF and LBM. LBM was assessed by
      anthropometry. In the survival study a BMI < 20 kg/m2 was associated with a low
      SMIP (p < 0.001) and reduced survival, whereas MIP was relatively preserved. In
      the cross-sectional study SMIP (p < 0.001), MIP (p < 0.01), and HG (p < 0.01)
      were all reduced in the low LBM group, but not when related to total LBM. C
      reactive protein and LBM were inversely related (r = -0.71, p < 0.01). Impaired
      IMF was chiefly a loss of sustained muscle contraction secondary to a reduced
      skeletal muscle mass, which may be related to pulmonary inflammation.

PMID- 9769292
TI  - Severity of airflow limitation is associated with severity of airway inflammation
      in smokers.
AB  - To investigate the relationship between airflow limitation and airway
      inflammation in smokers, we examined paraffin-embedded bronchial biopsies
      obtained from 30 smokers: 10 with severe airflow limitation, eight with
      mild/moderate airflow limitation, and 12 control smokers with normal lung
      function. Histochemical and immunohistochemical methods were performed to assess
      the number of inflammatory cells in the subepithelium and the expression of CC
      chemokines macrophage inflammatory protein (MIP)-1alpha and -1beta in the
      bronchial mucosa. Compared with control smokers, smokers with severe airflow
      limitation had an increased number of neutrophils (p < 0.02), macrophages (p <
      0.03), and NK lymphocytes (p < 0.03) in the subepithelium, and an increased
      number of MIP-1alpha+ epithelial cells (p < 0.02). When all smokers were
      considered together, the value of FEV1 was inversely correlated with the number
      of neutrophils (r = -0.59, p < 0.002), macrophages (r = -047, p < 0. 012), NK
      lymphocytes (r = -0.51, p < 0.006) in the subepithelium, and with the number of
      MIP-1alpha+ epithelial cells (r = -0.61, p < 0.003). We conclude that in smokers
      the severity of airflow limitation is correlated with the severity of airway
      inflammation and that severe airflow limitation is associated with an increased
      number of neutrophils, macrophages, NK lymphocytes, and MIP-1alpha+ cells in the
      bronchial mucosa.

PMID- 9769294
TI  - Serum and bronchoalveolar fluid KL-6 levels in patients with pulmonary alveolar
      proteinosis.
AB  - Pulmonary alveolar proteinosis (PAP) is a disease characterized by the filling of
      alveolar spaces with periodic acid-Schiff-positive proteinaceous material and by
      the hypertrophy of type II pneumocytes in the alveolar interstitium. To examine
      if KL-6, a mucinlike glycoprotein, is useful for the diagnosis of PAP and the
      estimation of its activity, serum KL-6 levels in patients with PAP were measured
      by an enzyme-linked immunosorbent assay and compared with those of patients with
      other lung diseases. Furthermore, to estimate the origin of KL-6 in some
      patients, measurements of KL-6 levels in bronchoalveolar lavage (BAL) fluid and
      immunohistochemical staining of the lung tissues with a monoclonal antibody to KL
      6 antigen were performed. Serum KL-6 levels in patients with PAP were extremely
      high and were significantly higher than those in patients with interstitial lung
      diseases in which elevation of serum KL-6 has been recognized. BAL-fluid KL-6
      levels in patients with PAP were higher than serum levels. Both serum and BAL
      fluid KL-6 levels in patients with PAP correlated well with the disease activity.
      Immunohistochemically, positive staining was observed in proliferating type II
      pneumocytes. These results suggest the usefulness of KL-6 measurement in the
      diagnosis and estimation of disease activity of PAP.

PMID- 9769293
TI  - Nonspecific interstitial pneumonia. Individualization of a clinicopathologic
      entity in a series of 12 patients.
AB  - Nonspecific interstitial pneumonia/fibrosis (NSIP) has recently been
      individualized within the group of idiopathic interstitial pneumonias mainly
      based on a pathologic pattern of temporally uniform lesions distinct from usual,
      desquamative, and acute interstitial pneumonia. We studied 12 consecutive
      patients with NSIP at lung biopsy done as a diagnostic procedure for idiopathic
      interstitial lung disease. The patients were six males and six females, aged 52.5
      +/- 11.8 yr. In 8 of 12 cases the pathologic lesions consisted of both cellular
      interstitial inflammation and fibrosis, whereas only cellular inflammation was
      present in three cases, and fibrosis in one. Dyspnea, cough, inspiratory
      crackles, and squeaks were the most common symptoms and signs. Six cases were
      cryptogenic. An associated disorder or a presumed cause was present in the other
      six patients, including underlying connective tissue disease (n = 3), organic
      dust exposure (n = 2), and prior acute lung injury (n = 1). Lung function tests
      found a restrictive ventilatory defect (11/12), impairment of TLCO (11/11), and
      hypoxemia at rest (7/12). Chest X-ray showed infiltrative opacities in all cases.
      Computed tomography of the chest in 11 cases mainly showed ground glass opacities
      (9/11), patchy areas of alveolar consolidation (6/ 11), and thickening of
      interlobular septas (5/11). All patients were treated with corticosteroids, and
      seven with immunosuppressive agents. All patients were alive at last follow-up,
      50 +/- 40 mo after diagnosis. Ten patients (83%) were clinically improved or
      stabilized. Thus, despite its heterogeneity, NSIP deserves to be individualized
      as an original clinicopathologic entity and should be clearly distinguished from
      usual interstitial pneumonia, especially because of a better prognosis.

PMID- 9769295
TI  - Influence of environmental concentrations of NO on the exhaled NO test.
AB  - Measurement of levels of exhaled nitric oxide (NO) has been proposed as a
      noninvasive method for evaluating the degree of airway inflammation in asthmatic
      patients. Some concern in the interpretation of results of such measurement may
      arise from possible interference by high environmental concentrations of NO
      inhaled by these patients. The aim of this study was to verify whether
      environmental concentrations of NO in the range from 0 to 150 ppb can influence
      levels of exhaled NO. We tested two groups of subjects. The first group,
      consisting of 16 subjects, was tested when environmental levels of NO were from 0
      to 3 ppb and from 20 to 60 ppb, and exhaled NO mean ppb (+/- SEM) levels were
      9.81 +/- 1.43 and 9.78 +/- 1.47 (p = ns) (mean +/- SEM), respectively. The second
      group, consisting of 30 subjects, was tested at ambient NO concentrations of 0 to
      3 ppm, 80 to 100 ppm, and 120 to 150 ppb, and for 18 of these subjects who
      underwent testing under all three conditions investigated, the mean levels of
      exhaled NO were 9.23 +/- 1.51, 7.78 +/- 1.19, and 9.33 +/- 1.55 ppb (p = ns),
      respectively. The results of this study suggest that significantly different
      ambient levels of NO have no effect on levels of exhaled NO.

PMID- 9769296
TI  - Diffuse alveolar hemorrhage with underlying pulmonary capillaritis in the
      retinoic acid syndrome.
AB  - All-trans-retinoic acid (ATRA) can induce a clinical remission in patients with
      acute promyelocytic leukemia. An adverse condition called "retinoic acid
      syndrome" limits this therapy. It is characterized by fever and respiratory
      distress, along with weight gain, pleural or pericardial effusions, peripheral
      edema, thromboembolic events, and intermittent hypotension. The lung disease has
      been previously ascribed to an infiltration of leukemic or maturing myeloid cells
      into lung parenchyma, which is sometimes associated with pleural effusions and
      diffuse alveolar hemorrhage. We report a case of retinoic acid syndrome in an 18
      yr-old woman who developed diffuse alveolar hemorrhage while being treated with
      ATRA for acute promyelocytic leukemia. An open lung biopsy revealed pulmonary
      capillaritis.

PMID- 9769297
TI  - Acute delirium as a manifestation of obstructive sleep apnea syndrome.
AB  - Cognitive deficits and psychiatric manifestations such as depression and
      psychosis have been associated with obstructive sleep apnea (OSA) syndrome. We
      report a patient with OSA admitted to our center because of acute delirium of
      sudden onset at night, during sleep, and which impelled the patient to jump out
      of the window of his home. After exhaustive study, no other causes were found for
      the delirium, which resolved when nasal continuous positive airway pressure
      (nCPAP) was initiated. We believe that it is clinically important to be aware of
      this association, since it identifies a new, treatable cause of delirium.

PMID- 9769298
TI  - From the microscope to the clinic: MR assessment of atherosclerotic plaque.

PMID- 9769299
TI  - Recombinant cardiac ATP-sensitive potassium channels and cardioprotection.

PMID- 9769300
TI  - Impaired platelet production of nitric oxide predicts presence of acute coronary
      syndromes.
AB  - BACKGROUND: Thrombus formation within a coronary vessel is the acute
      precipitating event in most acute coronary syndromes. Recently, constitutive
      nitric oxide synthase (cNOS) has been identified in human platelets, and platelet
      derived nitric oxide has been shown to inhibit platelet recruitment after
      aggregation. However, its role in regulating platelet responses under normal or
      pathologic conditions has not yet been elucidated. METHODS AND RESULTS: We
      examined nitric oxide (NO) production by platelets isolated from 87 patients
      undergoing coronary angiography, 37 with stable angina and 50 with unstable
      angina or a myocardial infarction within 2 weeks. After stimulation with 5
      micromol/L ADP, platelet aggregation and NO production were simultaneously
      measured with an NO-selective microelectrode adapted for use in a standard
      platelet aggregometer. Mean (+/-SEM) platelet-derived NO production was 1.78+/
      0.36 pmol/10(8) and 0.26+/-0.05 pmol/10(8) platelets in coronary patients with
      stable angina and acute coronary syndromes, respectively (P=0. 0001). By logistic
      regression analysis, heparin treatment (odds ratio 6.6, CI 1.9 to 22.8, P=0.003),
      lower platelet-NO production (odds ratio 4.0, CI 1.3 to 11.5, P=0.01), and extent
      of atherosclerosis (odds ratio 1.5, CI 1.1 to 2.0, P=0.02) were independent
      predictors of an acute coronary syndrome. In the subset of patients with
      angiographic evidence of atherosclerosis (n=83), logistic regression demonstrated
      that platelet NO production (odds ratio 3.9, CI 1.3 to 11.1, P=0.01) and heparin
      treatment (odds ratio 6.4, CI 1.9 to 22.0, P=0.004) were independent predictors
      of an acute coronary syndrome, whereas extent of atherosclerosis was not.
      CONCLUSIONS: In summary, aggregating platelets from patients with acute coronary
      syndromes produce less NO. Since platelet aggregation and thrombus formation are
      implicated in unstable angina and myocardial infarction, impaired platelet
      derived NO production may contribute to the development of acute coronary
      syndromes.

PMID- 9769301
TI  - Oxidized LDL and malondialdehyde-modified LDL in patients with acute coronary
      syndromes and stable coronary artery disease.
AB  - BACKGROUND: The association between oxidative modifications of LDL and coronary
      artery disease (CAD) is suspected but not established. Therefore, the association
      between plasma levels of oxidized LDL and malondialdehyde (MDA)-modified LDL and
      acute coronary syndromes and stable CAD was investigated. METHODS AND RESULTS:
      The study population contained 63 patients with acute coronary syndromes (45 with
      acute myocardial infarction and 18 with unstable angina pectoris), 35
      nontransplanted patients with angiographically confirmed stable angina, 28 heart
      transplant patients with posttransplant CAD, 79 heart transplant patients without
      CAD, and 65 control subjects. After correction for age, sex, and LDL and HDL
      cholesterol, plasma levels of oxidized LDL and MDA-modified LDL were
      significantly higher in patients with CAD than in individuals without CAD
      (r2=0.57 and r2=0.26, respectively; both P=0.0001). Plasma levels of MDA-modified
      LDL were significantly higher in patients with acute coronary syndromes than in
      individuals with stable CAD (r2=0.65; P=0.0001) and were associated with
      increased levels of troponin I and C-reactive protein (r2=0.39 and r2=0.34,
      respectively; both P=0.0001). Plasma levels of oxidized LDL were not associated
      with increased levels of troponin I and C-reactive protein (r2=0.089 and
      r2=0.063, respectively). CONCLUSIONS: Elevated plasma levels of oxidized LDL are
      associated with CAD. Elevated plasma levels of MDA-modified LDL suggest plaque
      instability and may be useful for the identification of patients with acute
      coronary syndromes.

PMID- 9769302
TI  - Coronary stents: In vitro aspects of an angiographic and ultrasound
      quantification with in vivo correlation.
AB  - BACKGROUND: The validity of quantitative coronary angiography (QCA) after stent
      placement has been questioned because the optical density of a metallic stent,
      added to the density of a contrast-filled lumen, could affect border definition.
      METHODS AND RESULTS: We deployed 3.0- and 4.0-mm Palmaz-Schatz, Wiktor,
      Multilink, NIR, and InStent stents in precision-cast phantoms. Central lumens of
      2.0 mm were created. There was no difference between the "true" diameters of any
      stented lumen by both QCA and quantitative ultrasonic (QCU) measurement
      poststenting. QCA systematic error (SE) varied from 0.01 for the Wiktor stents to
      0.14 mm for the Palmaz-Schatz stents; the random error (RE) was 0.03 to 0.14 mm.
      QCU SE varied from 0.05 to 0.11 mm, and RE ranged from 0.01 to 0.07 mm. At the
      next stage, 4.0-mm Wiktor and Palmaz-Schatz stents were deployed into the phantom
      lumens; 1.5-, 2.0-, 2.5- and 3.0-mm lumens were created inside the stents. QCA
      and QCU measurements of 1.5- to 2.5-mm residual lumens were overestimated by 0.1
      to 0.3 mm. In the 3. 0-mm residual lumen within the Wiktor stent, QCA
      underestimated the luminal size by -0.1 mm. There was no QCA inaccuracy for a 3.0
      mm lumen within the Palmaz-Schatz stent. In patients, in 25 stented segments in
      both the Palmaz-Schatz and Wiktor groups, there was no difference between QCA and
      QCU diameters. CONCLUSIONS: QCU is sufficiently precise for the assessment of the
      coronary lumen after stenting. QCA can be used as an accurate method of poststent
      assessment, except when a very mild recurrence within a highly opaque stent is
      measured. In that instance, QCA may underestimate the luminal diameter.

PMID- 9769303
TI  - Increased carotid artery intimal-medial thickness in asymptomatic older subjects
      with exercise-induced myocardial ischemia.
AB  - BACKGROUND: Previous studies have shown an association between symptomatic
      coronary artery disease (CAD) and increased intimal-medial thickness of the
      common carotid artery (CCA IMT), a purported index of atherosclerosis. This study
      determines whether CCA IMT is increased in asymptomatic older subjects with an
      ischemic ST-segment response to treadmill exercise. METHODS AND RESULTS: CCA IMT
      was measured by B-mode ultrasound in community-dwelling volunteers from the
      Baltimore Longitudinal Study of Aging, including 397 healthy subjects (age,
      58.5+/-15.8 years) with normal ECG responses to maximum treadmill exercise, 72
      asymptomatic subjects (age, 66.1+/-13.4 years) with exercise-induced horizontal
      or downsloping ST-segment depression >/=1 mm, and 38 subjects (age, 77. 4+/-7.8
      years) with clinically manifest CAD as diagnosed by medical history and resting
      ECG. Forty-three subjects with abnormal exercise ECGs also underwent exercise
      thallium scintigraphy. Exercise-induced ST-segment depression was associated with
      increased IMT (P<0.0001) independent of age and manifest CAD. After adjustment
      for age, IMT values progressively increased from healthy subjects to asymptomatic
      subjects with positive exercise ECG alone to those with concordant positive ECG
      and thallium scintigraphic findings who had virtually identical IMT to subjects
      with manifest CAD. Each 0.1-mm increase in IMT was associated with a 1.91-fold
      (95% CI, 1.46 to 2.50; P<0.0001) increased risk for concordant positive exercise
      tests or manifest CAD, independent of other significant predictors of CAD.
      CONCLUSIONS: CCA IMT is increased in older subjects with asymptomatic myocardial
      ischemia as evidenced by exercise ECG alone or in combination with thallium scan.
      Carotid ultrasound may help to identify asymptomatic individuals with CAD.

PMID- 9769304
TI  - Prospective study of heart rate variability and mortality in chronic heart
      failure: results of the United Kingdom heart failure evaluation and assessment of
      risk trial (UK-heart).
AB  - BACKGROUND: Patients with chronic heart failure (CHF) have a continuing high
      mortality. Autonomic dysfunction may play an important role in the
      pathophysiology of cardiac death in CHF. UK-HEART examined the value of heart
      rate variability (HRV) measures as independent predictors of death in CHF.
      METHODS AND RESULTS: In a prospective study powered for mortality, we recruited
      433 outpatients 62+/-9.6 years old with CHF (NYHA functional class I to III; mean
      ejection fraction, 0.41+/-0.17). Time-domain HRV indices and conventional
      prognostic indicators were related to death by multivariate analysis. During
      482+/-161 days of follow-up, cardiothoracic ratio, SDNN, left ventricular end
      systolic diameter, and serum sodium were significant predictors of all-cause
      mortality. The risk ratio for a 41.2-ms decrease in SDNN was 1.62 (95% CI, 1.16
      to 2.44). The annual mortality rate for the study population in SDNN subgroups
      was 5.5% for >100 ms, 12.7% for 50 to 100 ms, and 51.4% for <50 ms. SDNN,
      creatinine, and serum sodium were related to progressive heart failure death.
      Cardiothoracic ratio, left ventricular end-diastolic diameter, the presence of
      nonsustained ventricular tachycardia, and serum potassium were related to sudden
      cardiac death. A reduction in SDNN was the most powerful predictor of the risk of
      death due to progressive heart failure. CONCLUSIONS: CHF is associated with
      autonomic dysfunction, which can be quantified by measuring HRV. A reduction in
      SDNN identifies patients at high risk of death and is a better predictor of death
      due to progressive heart failure than other conventional clinical measurements.
      High-risk subgroups identified by this measurement are candidates for additional
      therapy after prescription of an ACE inhibitor.

PMID- 9769305
TI  - Gross and microscopic pathological changes associated with nonthoracotomy
      implantable defibrillator leads.
AB  - BACKGROUND: Although the effects of epicardial implantable cardioverter
      defibrillator (ICD) leads on underlying cardiac tissue have been reported, the
      gross and microscopic changes associated with endocardial ICD leads are less well
      described. This study describes the gross and microscopic changes associated with
      endocardial ICD leads in humans. METHODS AND RESULTS: The hearts from 8 patients
      were examined. At the time of ICD implantation, the patients' mean age was 47+/
      11 years, and the left ventricular ejection fraction was 0.24+/-0.10. Four
      patients had ischemic heart disease, and 4 had dilated cardiomyopathy. Five
      hearts were examined after transplantation; 3, after death. The electrode
      myocardial interfaces were characterized by intense endocardial fibrosis and were
      remarkably consistent. Each lead was encased by a ring of fibroelastic tissue,
      and there was fibrosis of the right ventricular myocardium adjacent to the leads.
      Fibrosis involved the tricuspid valve in 5 patients, and 1 had perforation of the
      valve by the lead. Microscopically, interstitial fibrosis was adjacent to each
      lead in the current path of ICD shocks. Acute cell injury was present only in the
      hearts that had received recent shocks. CONCLUSIONS: The ICD electrode-myocardial
      interface is characterized by intense fibrosis. The fibrosis associated with
      endocardial ICD leads and the cumulative acute damage produced by defibrillation
      discharges may explain changes in the defibrillation and pacing thresholds and
      the difficulty of lead extraction that can be encountered with transvenous ICD
      systems.

PMID- 9769306
TI  - Localization of optimal ablation site of idiopathic ventricular tachycardia from
      right and left ventricular outflow tract by body surface ECG.
AB  - BACKGROUND: Idiopathic ventricular tachycardia (VT) is known to arise from the
      right ventricular (RV) and left ventricular outflow tracts (LVOT). However,
      reliable noninvasive methods to localize the optimum ablation site for VT have
      not been reported. METHODS AND RESULTS: Body surface maps (BSM) and 12-lead ECGs
      were investigated in 35 VTs from the RVOT and 5 VTs from the LVOT in which the
      origin was confirmed during the ablation procedure. The RVOT was classified into
      8 subdivisions with the use of a 3-dimensional anatomic relation: anterior (A)
      posterior (P), right (R) left (L), and superior (S) inferior (I). On the BSM, the
      following 3 indexes differentiated each location of the origin, with a diagnostic
      accuracy of 88% (A-P), 92% (R-L), and 77% (S-I): (1) the location of the minimum
      at the early-to-mid QRS (right, A; left, P), (2) the isopotential distribution in
      the left shoulder area after 30 ms of QRS (positive, R; negative, L), and (3) the
      downward moving time of the minimum at the early-to-mid QRS (>/=50 ms, S; <50 ms,
      I). On the 12-lead ECG, (1) the QRS duration (>140 ms, A; </=140 ms, P) and the R
      wave pattern in leads II and III (RR' or Rr', A, R, P), (2) the QS wave amplitude
      in aVR and aVL (aVR>/=aVL, R; aVR<aVL, L), and (3) the r-wave amplitude in V1 and
      V2 (high, S; low, I) localized the origin with 80%, 86% (A-P), 80% (R-L), and 66%
      (S-I) accuracy. R/S>/=1 in lead V3 was an index suggesting the LVOT origin.
      CONCLUSIONS: The origin or the optimum ablation site of idiopathic VT from RVOT
      and LVOT can be localized with the use of indexes obtained with a BSM or 12-lead
      ECG.

PMID- 9769307
TI  - Risk to patients from radiation associated with radiofrequency ablation for
      supraventricular tachycardia.
AB  - BACKGROUND: Radiofrequency ablation may be associated with prolonged fluoroscopy
      times. Previous studies have calculated radiation risks by measuring the
      radiation dose at a limited number (6) of body sites. This is an inherently
      inaccurate measure. Our study aimed to quantify more precisely patient-related
      radiation risks associated with radiofrequency ablation for supraventricular
      tachycardia. METHODS AND RESULTS: Nine female patients having radiofrequency
      ablation for supraventricular tachycardia were studied. The radiation dose was
      determined at 41 body sites in each patient with the use of thermoluminescent
      dosimeters and was correlated with that measured simultaneously with a Diamentor
      dose-area product meter. The estimated mean organ doses (mGy) per 60 minutes of
      fluoroscopy were: lungs 30.8; bone marrow 4.3; left breast 5.1; right breast 3.
      5; and thyroid 2.4. From the average organ doses, the estimated mean total
      lifetime excess risk of a fatal malignancy was 294 per million cases (0.03%) per
      60 minutes of fluoroscopy. The risk calculation from the Diamentor dose-area
      product and thermoluminescent dosimeters were similar, suggesting that radiation
      dose was measured accurately. The estimated risk of radiation-induced malignancy
      increased with increasing body mass index (P=0.03). CONCLUSIONS: Prolonged
      fluoroscopy during radiofrequency ablation may potentially cause a small increase
      in the lifetime risk of fatal malignancy, with lung malignancy being most likely.
      This risk is small only with the use of techniques and x-ray equipment optimized
      to keep radiation as low as possible. The risk is increased in obese patients.

PMID- 9769308
TI  - Noninvasive In vivo high-resolution magnetic resonance imaging of atherosclerotic
      lesions in genetically engineered mice.
AB  - BACKGROUND: The pathogenesis of atherosclerosis is currently being investigated
      in genetically engineered small animals. Methods to follow the time course of the
      developing pathology and/or the responses to therapy in vivo are limited. METHODS
      AND RESULTS: To address this problem, we developed a noninvasive MR microscopy
      technique to study in vivo atherosclerotic lesions (without a priori knowledge of
      the lesion location or lesion type) in live apolipoprotein E knockout (apoE-KO)
      mice. The spatial resolution was 0.0012 to 0.005 mm3. The lumen and wall of the
      abdominal aorta and iliac arteries were identified on all images in apoE-KO (n=8)
      and wild-type (n=5) mice on chow diet. Images obtained with MR were compared with
      corresponding cross-sectional histopathology (n=58). MR accurately determined
      wall area in comparison to histopathology (slope=1.0, r=0.86). In addition,
      atherosclerotic lesions were characterized in terms of lesion shape and type.
      Lesion type was graded by MR according to morphological appearance/severity and
      by histopathology according to the AHA classification. There was excellent
      agreement between MR and histopathology in grading of lesion shape and type
      (slope=0.97, r=0.91 for lesion shape; slope=0. 64, r=0.90 for lesion type).
      CONCLUSIONS: The combination of high-resolution MR microscopy and genetically
      engineered animals is a powerful tool to investigate serially and noninvasively
      the progression and regression of atherosclerotic lesions in an intact animal
      model and should greatly enhance basic studies of atherosclerotic disease.

PMID- 9769309
TI  - Recombinant cardiac ATP-sensitive K+ channel subunits confer resistance to
      chemical hypoxia-reoxygenation injury.
AB  - BACKGROUND: Opening of cardiac ATP-sensitive K+ (KATP) channels has emerged as a
      promising but still controversial cardioprotective mechanism. Defining KATP
      channel function at the level of recombinant channel proteins is a necessary step
      toward further evaluation of the cardioprotective significance of this ion
      conductance. METHODS AND RESULTS: KATP channel deficient COS-7 cells were found
      to be vulnerable to chemical hypoxia-reoxygenation injury that induced
      significant cytosolic Ca2+ loading (from 97+/-3 to 236+/-11 nmol/L). In these
      cells, the potassium channel opener pinacidil (10 micromol/L) did not prevent
      Ca2+ loading (from 96+/-3 nmol/L before to 233+/-12 nmol/L after reoxygenation)
      or evoked membrane current. Cotransfection with Kir6.2/SUR2A genes, which encode
      cardiac KATP channel subunits, resulted in a cellular phenotype that, in the
      presence of pinacidil (10 micromol/L), expressed K+ current and gained resistance
      to hypoxia-reoxygenation (Ca2+ concentration from 99+/-7 to 127+/-11 nmol/L;
      P>0.05). Both properties were abolished by the KATP channel blocker glyburide (1
      micromol/L). In COS-7 cells transfected with individual channel subunits Kir6.2
      or SUR2A, which alone do not form functional cardiac KATP channels, pinacidil did
      not protect against hypoxia-reoxygenation. CONCLUSIONS: The fact that transfer of
      cardiac KATP channel subunits protected natively KATP channel deficient cells
      provides direct evidence that the cardiac KATP channel protein complex harbors
      intrinsic cytoprotective properties. These findings validate the concept that
      targeting cardiac KATP channels should be considered a valuable approach to
      protect the myocardium against injury.

PMID- 9769310
TI  - Transmembrane potential properties at the core of functional reentrant wave
      fronts in isolated canine right atria.
AB  - BACKGROUND: The characteristics of transmembrane potential (TMP) at the core of
      functional reentry in the atrium are not well understood. METHODS AND RESULTS: In
      protocol 1 (11 dogs), isolated perfused canine right atria were mapped from the
      endocardial surface while simultaneous TMPs were recorded from the epicardial
      surface. Episodes of reentry (n=64) were induced in the presence of 1 to 5
      micromol/L acetylcholine. Successful simultaneous TMP recordings and activation
      maps were made in 8 episodes. The TMP was "near the core" if it was within 3.2 mm
      of the core; otherwise, it was considered to be "in the periphery." The mean
      cycle length of reentry was 110+/-35 ms. The TMP amplitude, duration (90%
      repolarization), and (dV/dt)max near the core (n=106) were 58+/-22 mV, 46+/-14
      ms, and 33+/-20 V/s, respectively, significantly less than those in the periphery
      (n=241): 70+/-8 mV, 94+/-32 ms, and 55+/-10 V/s (P<0.001 for all). In 2 episodes
      of reentry, the cell at the core remained unexcited at its resting membrane
      potential. In protocol 2 (2 dogs), we performed simultaneous high-density mapping
      in 4 episodes of reentry and showed synchronous activation patterns on both
      surfaces with similar locations of the core. CONCLUSIONS: During meandering
      functional reentry in isolated canine right atria, (1) TMPs of cells near the
      core have a reduced amplitude, duration, and (dV/dt)max, and (2) cells at the
      core may remain unexcited at their resting membrane potential. These findings are
      compatible with the spiral wave concept of functional reentry in the atrium.

PMID- 9769312
TI  - Low-molecular-weight heparin : A review of the results of recent studies of the
      treatment of venous thromboembolism and unstable angina.

PMID- 9769311
TI  - Jarvik 2000 heart: potential for bridge to myocyte recovery.
AB  - BACKGROUND: Mechanical bridge to left ventricular recovery is an emerging
      strategy for the treatment of heart failure. We sought to validate the use of a
      new intracardiac axial flow impeller pump for this purpose. METHODS AND RESULTS:
      The Jarvik 2000 Heart was implanted into 30 sheep to ascertain mechanical
      reliability, biocompatibility, and hemodynamic function. We attempted but failed
      to anticoagulate with warfarin. Elective explants with survival were performed in
      3 animals to simulate bridge to recovery. Extensive autopsy studies were
      performed in all other animals. At speeds between 8000 and 12 000 rpm the device
      pumped up to 8 L/min, captured all mitral flow, and augmented cardiac output with
      elevation of mean arterial pressure. The pump was silent and hemolysis
      negligible. Nonpulsatile flow did not adversely affect neurological or renal
      function. Device removal proved straightforward and safe. A fractured inflow
      bearing occurred in 1 early model. There were no other pump failures, but power
      interruption occurred when the sheep chewed the cables or head-butted the
      percutaneous pedestal. At autopsy, there was no thromboembolism or primary
      thrombus formation in any device. Pump occlusion occurred in 2 sheep with
      bacterial endocarditis. One electively explanted pump, previously switched off
      for 5 months, had no thrombus in the device or vascular graft. CONCLUSIONS: The
      Jarvik 2000 Heart is a major advance in blood-pump technology and increases the
      scope of mechanical circulatory support. Reliability and ease of removal favor
      its use for bridge to myocyte recovery, as well as for bridge to transplantation
      or long-term support.

PMID- 9769313
TI  - Images in Cardiovascular Medicine. Scimitar syndrome.

PMID- 9769314
TI  - Images in Cardiovascular Medicine. Ultrasonographic images of Takayasu's
      arteritis.

PMID- 9769315
TI  - Percutaneous treatment of left main coronary stenosis.

PMID- 9769316
TI  - Acetylcholine and endothelial function 

PMID- 9769317
TI  - Heart rate variability standards.

PMID- 9769318
TI  - Role of lymphocytes in heart disease.

PMID- 9769319
TI  - Interaction between neuronal nitric oxide synthase and inhibitory G protein
      activity in heart rate regulation in conscious mice.
AB  - Nitric oxide (NO) synthesized within mammalian sinoatrial cells has been shown to
      participate in cholinergic control of heart rate (HR). However, it is not known
      whether NO synthesized within neurons plays a role in HR regulation. HR dynamics
      were measured in 24 wild-type (WT) mice and 24 mice in which the gene for
      neuronal NO synthase (nNOS) was absent (nNOS-/- mice). Mean HR and HR variability
      were compared in subsets of these animals at baseline, after parasympathetic
      blockade with atropine (0.5 mg/kg i.p.), after beta-adrenergic blockade with
      propranolol (1 mg/kg i.p.), and after combined autonomic blockade. Other animals
      underwent pressor challenge with phenylephrine (3 mg/kg i.p.) after beta
      adrenergic blockade to test for a baroreflex-mediated cardioinhibitory response.
      The latter experiments were then repeated after inactivation of inhibitory G
      proteins with pertussis toxin (PTX) (30 microgram/kg i.p.). At baseline, nNOS-/-
      mice had higher mean HR (711+/-8 vs. 650+/-8 bpm, P = 0.0004) and lower HR
      variance (424+/-70 vs. 1,112+/-174 bpm2, P = 0.001) compared with WT mice. In
      nNOS-/- mice, atropine administration led to a much smaller change in mean HR (
      2+/-9 vs. 49+/-5 bpm, P = 0.0008) and in HR variance (64+/-24 vs. -903+/-295
      bpm2, P = 0.02) than in WT mice. In contrast, propranolol administration and
      combined autonomic blockade led to similar changes in mean HR between the two
      groups. After beta-adrenergic blockade, phenylephrine injection elicited a fall
      in mean HR and rise in HR variance in WT mice that was partially attenuated after
      treatment with PTX. The response to pressor challenge in nNOS-/- mice before PTX
      administration was similar to that in WT mice. However, PTX-treated nNOS-/- mice
      had a dramatically attenuated response to phenylephrine. These findings suggest
      that the absence of nNOS activity leads to reduced baseline parasympathetic tone,
      but does not prevent baroreflex-mediated cardioinhibition unless inhibitory G
      proteins are also inactivated. Thus, neuronally derived NO and cardiac inhibitory
      G protein activity serve as parallel pathways to mediate autonomic slowing of
      heart rate in the mouse.

PMID- 9769320
TI  - Paternal mutation of the sulfonylurea receptor (SUR1) gene and maternal loss of
      11p15 imprinted genes lead to persistent hyperinsulinism in focal adenomatous
      hyperplasia.
AB  - Congenital hyperinsulinism, or persistent hyperinsulinemic hypoglycemia of
      infancy (PHHI), is a glucose metabolism disorder characterized by unregulated
      secretion of insulin and profound hypoglycemia. From a morphological standpoint,
      there are two types of histopathological lesions, a focal adenomatous hyperplasia
      of islet cells of the pancreas in approximately 30% of operated sporadic cases,
      and a diffuse form. In sporadic focal forms, specific losses of maternal alleles
      (LOH) of the imprinted chromosomal region 11p15, restricted to the hyperplastic
      area of the pancreas, were observed. Similar mechanisms are observed in embryonal
      tumors and in the Beckwith-Wiedemann syndrome (BWS), also associated with
      neonatal but transient hyperinsulinism. However, this region also contains the
      sulfonylurea receptor (SUR1) gene and the inward rectifying potassium channel
      subunit (KIR6.2) gene, involved in recessive familial forms of PHHI, but not
      known to be imprinted. Although the parental bias in loss of maternal alleles did
      not argue in favor of their direct involvement, the LOH may also unmask a
      recessive mutation leading to persistent hyperinsulinism. We now report somatic
      reduction to hemizygosity or homozygosity of a paternal SUR1 constitutional
      heterozygous mutation in four patients with a focal form of PHHI. Thus, this
      somatic event which leads both to beta cell proliferation and to hyperinsulinism
      can be considered as the somatic equivalent, restricted to a microscopic focal
      lesion, of constitutional uniparental disomy associated with unmasking of a
      heterozygous parental mutation leading to a somatic recessive disorder.

PMID- 9769321
TI  - A mouse model of myosin binding protein C human familial hypertrophic
      cardiomyopathy.
AB  - Familial hypertrophic cardiomyopathy can be caused by mutations in genes encoding
      sarcomeric proteins, including the cardiac isoform of myosin binding protein C
      (MyBP-C), and multiple mutations which cause truncated forms of the protein to be
      made are linked to the disease. We have created transgenic mice in which varying
      amounts of a mutated MyBP-C, lacking the myosin and titin binding domains, are
      expressed in the heart. The transgenically encoded, truncated protein is stable
      but is not incorporated efficiently into the sarcomere. The transgenic muscle
      fibers showed a leftward shift in the pCa2+-force curve and, importantly, their
      power output was reduced. Additionally, expression of the mutant protein leads to
      decreased levels of endogenous MyBP-C, resulting in a striking pattern of
      sarcomere disorganization and dysgenesis.

PMID- 9769322
TI  - Reduced microvascular thrombosis and improved outcome in acute murine stroke by
      inhibiting GP IIb/IIIa receptor-mediated platelet aggregation.
AB  - Treatment options in acute stroke are limited by a dearth of safe and effective
      regimens for recanalization of an occluded cerebrovascular tributary, as well as
      by the fact that patients present only after the occlusive event is established.
      We hypothesized that even if the site of major arterial occlusion is recanalized
      after stroke, microvascular thrombosis continues to occur at distal sites,
      reducing postischemic flow and contributing to ongoing neuronal death. To test
      this hypothesis, and to show that microvascular thrombosis occurs as an ongoing,
      dynamic process after the onset of stroke, we tested the effects of a potent
      antiplatelet agent given both before and after the onset of middle cerebral
      arterial (MCA) occlusion in a murine model of stroke. After 45 min of MCA
      occlusion and 23 h of reperfusion, fibrin accumulates in the ipsilateral cerebral
      hemisphere, based upon immunoblotting, and localizes to microvascular lumena,
      based upon immunostaining. In concordance with these data, there is a nearly
      threefold increase in the ipsilateral accumulation of 111In-labeled platelets in
      mice subjected to stroke compared with mice not subjected to stroke. When a novel
      inhibitor of the glycoprotein IIb/IIIa receptor (SDZ GPI 562) was administered
      immediately before MCA occlusion, platelet accumulation was reduced 48%, and
      fibrin accumulation was reduced by 47% by immunoblot densitometry. GPI 562
      exhibited a dose-dependent reduction of cerebral infarct volumes measured by
      triphenyltetrazolium chloride staining, as well as improvement in postischemic
      cerebral blood flow, measured by laser doppler. GPI 562 caused a dose-dependent
      increase in tail vein bleeding time, but intracerebral hemorrhage (ICH) was not
      significantly increased at therapeutic doses; however, there was an increase in
      ICH at the highest doses tested. When given immediately after withdrawal of the
      MCA occluding suture, GPI 562 was shown to reduce cerebral infarct volumes by
      70%. These data support the hypothesis that in ischemic regions of brain,
      microvascular thrombi continue to accumulate even after recanalization of the
      MCA, contributing to postischemic hypoperfusion and ongoing neuronal damage.

PMID- 9769323
TI  - Role of the stress-activated protein kinases in endothelin-induced cardiomyocyte
      hypertrophy.
AB  - The signal transduction pathways governing the hypertrophic response of
      cardiomyocytes are not well defined. Constitutive activation of the stress
      activated protein kinase (SAPK) family of mitogen-activated protein (MAP) kinases
      or another stress-response MAP kinase, p38, by overexpression of activated
      mutants of various components of the pathways is sufficient to induce a
      hypertrophic response in cardiomyocytes, but it is not clear what role these
      pathways play in the response to physiologically relevant hypertrophic stimuli.
      To determine the role of the SAPKs in the hypertrophic response, we used
      adenovirus-mediated gene transfer of SAPK/ERK kinase-1 (KR) [SEK-1(KR)], a
      dominant inhibitory mutant of SEK-1, the immediate upstream activator of the
      SAPKs, to block signal transmission down the SAPK pathway in response to the
      potent hypertrophic agent, endothelin-1 (ET-1). SEK-1(KR) completely inhibited ET
      1-induced SAPK activation without affecting activation of the other MAP kinases
      implicated in the hypertrophic response, p38 and extracellular signal-regulated
      protein kinases (ERK)-1/ERK-2. Expression of SEK-1(KR) markedly inhibited the ET
      1-induced increase in protein synthesis. In contrast, the MAPK/ERK kinase
      inhibitor, PD98059, which blocks ERK activation, and the p38 inhibitor, SB203580,
      had no effect on ET-1-induced protein synthesis. ET-1 also induced a significant
      increase in atrial natriuretic factor mRNA expression as well as in the
      percentage of cells with highly organized sarcomeres, responses which were also
      blocked by expression of SEK-1(KR). In summary, inhibiting activation of the SAPK
      pathway abrogated the hypertrophic response to ET-1. These data are the first
      demonstration that the SAPKs are necessary for the development of agonist-induced
      cardiomyocyte hypertrophy, and suggest that in response to ET-1, they transduce
      critical signals governing the hypertrophic response.

PMID- 9769324
TI  - Matrilysin expression and function in airway epithelium.
AB  - We report that matrilysin, a matrix metalloproteinase, is constitutively
      expressed in the epithelium of peribronchial glands and conducting airways in
      normal lung. Matrilysin expression was increased in airway epithelial cells and
      was induced in alveolar type II cells in cystic fibrosis. Other
      metalloproteinases (collagenase-1, stromelysin-1, and 92-kD gelatinase) were not
      produced by normal or injured lung epithelium. These observations suggest that
      matrilysin functions in injury-mediated responses of the lung. Indeed, matrilysin
      expression was increased in migrating airway epithelial cells in wounded human
      and mouse trachea. In human tissue, epithelial migration was reduced by > 80% by
      a hydroxamate inhibitor, and in mouse tissue, reepithelialization in trachea from
      matrilysin-null mice was essentially blocked. In vivo observations and cell
      culture studies demonstrated that matrilysin was secreted lumenally by lung
      epithelium, but upon activation or while migrating over wounds, some matrilysin
      was released basally. The constitutive production of matrilysin in conducting
      airways, its upregulation after injury, its induction by alveolar epithelium, and
      its release into both lumenal and matrix compartments suggest that this
      metalloproteinase serves multiple functions in intact and injured lung, one of
      which is to facilitate reepithelialization.

PMID- 9769325
TI  - Reduced binding and phagocytosis of Pneumocystis carinii by alveolar macrophages
      from persons infected with HIV-1 correlates with mannose receptor downregulation.
AB  - The macrophage mannose receptor, a pattern recognition molecule and component of
      innate immunity, mediates binding and phagocytosis of Pneumocystis carinii and
      likely represents an important clearance mechanism in the lungs of
      immunocompetent hosts. The purpose of this study was to examine the ability of
      alveolar macrophages from HIV-infected individuals to bind and phagocytose P.
      carinii, and to investigate the role of the macrophage mannose receptor in
      mediating this interaction. Compared with healthy individuals, alveolar
      macrophage phagocytosis of P. carinii from HIV+ persons was reduced up to 74% (P
      = 0.02), primarily reflecting a reduction in the number of organisms associated
      with each macrophage (P = 0.019). Furthermore, macrophages from HIV+ individuals
      demonstrated up to an 80% (P < 0.05) reduction in mannose receptor surface
      expression and endocytosis. Mannose receptor affinity was unaltered, and mRNA
      levels were modestly reduced (P < 0.05). Cells from HIV+ individuals with CD4(+)
      counts < 200 cells/mm3 (representing individuals at high clinical risk for P.
      carinii pneumonia) demonstrated the lowest levels of P. carinii phagocytosis and
      mannose receptor endocytosis. In vitro HIV infection of alveolar macrophages from
      healthy individuals reduced mannose receptor endocytosis to 53.2% (P < 0.05) and
      P. carinii binding and phagocytosis to 67.4% (P < 0.05) of control. Our studies
      suggest that HIV infection may alter innate immunity in the lungs, and that
      impaired alveolar macrophage mannose receptor-mediated binding and phagocytosis
      of P. carinii may contribute to the susceptibility of HIV-infected individuals to
      this opportunistic pulmonary pathogen.

PMID- 9769326
TI  - Effects of mutations in the human uncoupling protein 3 gene on the respiratory
      quotient and fat oxidation in severe obesity and type 2 diabetes.
AB  - Human uncoupling protein 3 (UCP3) is a mitochondrial transmembrane carrier that
      uncouples oxidative ATP phosphorylation. With the capacity to participate in
      thermogenesis and energy balance, UCP3 is an important obesity candidate gene. A
      missense polymorphism in exon 3 (V102I) was identified in an obese and diabetic
      proband. A mutation introducing a stop codon in exon 4 (R143X) and a terminal
      polymorphism in the splice donor junction of exon 6 were also identified in a
      compound heterozygote that was morbidly obese and diabetic. Allele frequencies of
      the exon 3 and exon 6 splice junction polymorphisms were determined and found to
      be similar in Gullah-speaking African Americans and the Mende tribe of Sierra
      Leone, but absent in Caucasians. Moreover, in exon 6-splice donor heterozygotes,
      basal fat oxidation rates were reduced by 50%, and the respiratory quotient was
      markedly increased compared with wild-type individuals, implicating a role for
      UCP3 in metabolic fuel partitioning.

PMID- 9769327
TI  - A novel phenotype related to partial loss of function mutations of the follicle
      stimulating hormone receptor.
AB  - A single natural loss of function mutation of the follicle stimulating hormone
      receptor (FSHR) has been described to date. Present in the Finnish population it
      markedly impairs receptor function, blocking follicle development at the primary
      stage and presenting as primary amenorrhea with atrophic ovaries. When Western
      European women with this phenotype were examined for FSHR mutations the result
      was negative, suggesting that other etiologies corresponding to this clinical
      pattern are markedly more frequent. We now describe a novel phenotype related to
      mutations provoking a partial loss of function of the FSHR. A woman with
      secondary amenorrhea had very high plasma gonadotropin concentrations (especially
      FSH), contrasting with normal sized ovaries and antral follicles up to 5 mm at
      ultrasonography. Histological and immunohistochemical examination of the ovaries
      showed normal follicular development up to the small antral stage and a
      disruption at further stages. The patient was found to carry compound
      heterozygotic mutations of the FSHR gene: Ile160Thr and Arg573Cys substitutions
      located, respectively, in the extracellular domain and in the third intracellular
      loop of the receptor. The mutated receptors, when expressed in COS-7 cells,
      showed partial functional impairment, consistent with the clinical and
      histological observations: the first mutation impaired cell surface expression
      and the second altered signal transduction of the receptor. This observation
      suggests that a limited FSH effect is sufficient to promote follicular growth up
      to the small antral stage. Further development necessitates strong FSH
      stimulation. The contrast between very high FSH levels and normal sized ovaries
      with antral follicles may thus be characteristic of such patients.

PMID- 9769328
TI  - Cloning and identification of human Sca as a novel inhibitor of osteoclast
      formation and bone resorption.
AB  - Increased osteoclast activity is responsible for the enhanced bone destruction in
      postmenopausal osteoporosis, Paget's disease, bone metastasis, and hypercalcemia
      of malignancy. However, the number of known inhibitory factors that block
      osteoclast formation and bone resorption are limited. Therefore, we used an
      expression-cloning approach to identify novel factors produced by osteoclasts
      that inhibit osteoclast activity. A candidate clone was identified and isolated
      from a human osteoclast-like multinucleated cell (MNC) cDNA library, named
      osteoclast inhibitory peptide-1 (OIP-1), and the cDNA sequence was determined.
      This sequence matched that of the recently identified human stem cell antigen,
      was structurally similar to the mouse Ly-6 gene family, and the sequence
      predicted it was a glycosyl phosphatidyl inositol (GPI)-anchored protein that had
      a cleavable COOH-terminal peptide. Western blot analysis of conditioned media
      from 293 cells transfected with the OIP-1 cDNA clone confirmed that OIP-1 was
      released into the media as a membrane-bound GPI-linked protein. Interestingly,
      both recombinant OIP-1 expressed in Escherichia coli (which does not have GPI
      linker) and OIP-1 expressed by mammalian cells significantly reduced osteoclast
      like MNC formation induced by 1,25-dihydroxyvitamin D3 or PTH-related protein in
      mouse and human bone marrow cultures, and inhibited 45Ca release from prelabeled
      bone in fetal rat organ cultures. In contrast, recombinant OIP-1 did not inhibit
      the growth of a variety of other cell types. These data indicate that OIP-1 is a
      novel, specific inhibitor of osteoclast formation and bone resorption.

PMID- 9769329
TI  - The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6
      transcription and plasma IL-6 levels, and an association with systemic-onset
      juvenile chronic arthritis.
AB  - During active disease, patients with systemic-onset juvenile chronic arthritis (S
      JCA) demonstrate a rise and fall in serum interleukin-6 (IL-6) that parallels the
      classic quotidian fever. To investigate the possibility that this cytokine
      profile results from a difference in the control of IL-6 expression, we examined
      the 5' flanking region of the IL-6 gene for polymorphisms. A G/C polymorphism was
      detected at position -174. In a group of 383 healthy men and women from a general
      practice in North London, the frequency of the C allele was 0.403 (95% confidence
      interval 0.37-0.44). In comparison, 92 patients with S-JCA had a different
      overall genotype frequency, especially those with onset of disease at < 5 yr of
      age. This was mainly due to the statistically significant lower frequency of the
      CC genotype in this subgroup. When comparing constructs of the 5' flanking region
      (-550-+61 bp) in a luciferase reporter vector transiently transfected into HeLa
      cells, the -174C construct showed 0.624+/-0.15-fold lower expression than the 
      174G construct. After stimulation with LPS or IL-1, expression from the -174C
      construct did not significantly change after 24 h, whereas expression from the 
      174G construct increased by 2.35+/-0.10- and 3.60+/-0.26-fold, respectively,
      compared with the unstimulated level. Plasma levels of IL-6 were also measured in
      102 of the healthy subjects, and the C allele was found to be associated with
      significantly lower levels of plasma IL-6. These results suggest that there is a
      genetically determined difference in the degree of the IL-6 response to stressful
      stimuli between individuals. The reduced frequency of the potentially protective
      CC genotype in young S-JCA patients may contribute to its pathogenesis. Similarly
      the individual's IL-6 genotype may be highly relevant in other conditions where
      IL-6 has been implicated, such as atherosclerosis.

PMID- 9769331
TI  - Requirement of Stat3 but not Stat1 activation for epidermal growth factor
      receptor- mediated cell growth In vitro.
AB  - Stimulation of epidermal growth factor receptor (EGFR) by ligand(s) leads to
      activation of signaling molecules including Stat1 and Stat3, two members of the
      signal transducers and activators of transcription (STAT) protein family.
      Activation of Stat1 and Stat3 was constitutive in transformed squamous epithelial
      cells, which produce elevated levels of TGF-alpha, and was enhanced by the
      addition of exogenous TGF-alpha. Targeting of Stat3 using antisense
      oligonucleotides directed against the translation initiation site, resulted in
      significant growth inhibition. In addition, cells stably transfected with
      dominant negative mutant Stat3 constructs failed to proliferate in vitro. In
      contrast, targeting of Stat1 using either antisense or dominant-negative
      strategies had no effect on cell growth. Thus, TGF-alpha/EGFR-mediated autocrine
      growth of transformed epithelial cells is dependent on activation of Stat3 but
      not Stat1.

PMID- 9769330
TI  - The negative inotropic effect of beta3-adrenoceptor stimulation is mediated by
      activation of a nitric oxide synthase pathway in human ventricle.
AB  - Beta1- and beta2-adrenoceptors in heart muscle cells mediate the catecholamine
      induced increase in the force and frequency of cardiac contraction. Recently, in
      addition, we demonstrated the functional expression of beta3-adrenoceptors in the
      human heart. Their stimulation, in marked contrast with that of beta1- and beta2
      adrenoceptors, induces a decrease in contractility through presently unknown
      mechanisms. In the present study, we examined the role of a nitric oxide (NO)
      synthase pathway in mediating the beta3-adrenoceptor effect on the contractility
      of human endomyocardial biopsies. The negative inotropic effects of a beta3
      adrenoceptor agonist, BRL 37344, and also of norepinephrine in the presence of
      alpha- and beta1-2-blockade were inhibited both by a nonspecific blocker of NO,
      methylene blue, and two NO synthase (NOS) inhibitors, L-N-monomethyl-arginine and
      L-nitroarginine-methyl ester. The effect of the NOS inhibitors was reversed by an
      excess of L-arginine, the natural substrate of NOS, but not by D-arginine.
      Moreover, the effects of the beta3-adrenoceptor agonist on contractility were
      associated with parallel increases in the production of NO and intracellular
      cGMP, which were also inhibited by NOS inhibitors. Immunohistochemical staining
      of human ventricular biopsies showed the expression of the endothelial
      constitutive (eNOS), but not the inducible (iNOS) isoform of NOS in both
      ventricular myocytes and endothelial cells. These results demonstrate that beta3
      adrenoceptor stimulation decreases cardiac contractility through activation of an
      NOS pathway. Changes in the expression of this pathway may alter the balance
      between positive and negative inotropic effects of catecholamines on the heart
      potentially leading to myocardial dysfunction.

PMID- 9769332
TI  - Autoreactive T cells to platelet GPIIb-IIIa in immune thrombocytopenic purpura.
      Role in production of anti-platelet autoantibody.
AB  - T cell proliferative responses to platelet membrane GPIIb-IIIa were examined in
      14 patients with chronic immune thrombocytopenic purpura (ITP), 7 systemic lupus
      erythematosus (SLE) patients with or without thrombocytopenia, and 10 healthy
      donors. Although peripheral blood T cells from all subjects failed to respond to
      the protein complex in its native state, reduced GPIIb-IIIa stimulated T cells
      from three ITP patients and one SLE patient with thrombocytopenia, and tryptic
      peptides of GPIIb-IIIa stimulated T cells from nearly all subjects. The
      specificity of the responses for GPIIb-IIIa was confirmed by activation of GPIIb
      IIIa-primed T cells by a recombinant GPIIbalpha fragment in secondary cultures.
      Characterization of T cell response induced by modified GPIIb-IIIa showed that
      the response was restricted by HLA-DR, the responding T cells had a CD4(+)
      phenotype, and the proliferation was accelerated only in ITP patients, suggesting
      in vivo activation of these T cells. In vitro IgG anti-GPIIb-IIIa synthesis in
      PBMC cultures was induced by modified GPIIb-IIIa specifically in ITP patients
      with platelet-associated anti-GPIIb-IIIa antibody. Anti-GPIIb-IIIa antibody
      produced in supernatants was absorbed by incubation with normal platelets. In
      summary, CD4(+) and HLA-DR-restricted T cells to GPIIb-IIIa are involved in
      production of anti-platelet autoantibody in ITP patients and are related to the
      pathogenic process in chronic ITP.

PMID- 9769333
TI  - Central nervous system nitric oxide synthase activity regulates insulin secretion
      and insulin action.
AB  - Systemic inhibition of nitric oxide synthase (NOS) with NG-monomethyl-L-arginine
      (L-NMMA) causes acute insulin resistance (IR), but the mechanism is unknown. We
      tested whether L-NMMA-induced IR occurs via NOS blockade in the central nervous
      system (CNS). Six groups of Sprague-Dawley rats were studied after chronic
      implantation of an intracerebroventricular (ICV) catheter into the lateral
      ventricle and catheters into the carotid artery and jugular vein. Animals were
      studied after overnight food deprivation, awake, unrestrained, and unstressed;
      all ICV infusion of L-NMMA or D-NMMA (control) were performed with artificial
      cerebrospinal fluid. ICV administration of L-NMMA resulted in a 30% rise in the
      basal glucose level after 2 h, while ICV D-NMMA had no effect on glucose levels.
      Insulin, epinephrine, and norepinephrine levels were unchanged from baseline in
      both groups. Tracer (3H-3-glucose)-determined glucose disposal rates during 2 h
      euglycemic hyperinsulinemic (300 microU/ml) clamps performed after ICV
      administration of L-NMMA were reduced by 22% compared with D-NMMA. Insulin
      secretory responses to a hyperglycemic clamp and to a superimposed arginine bolus
      were reduced by 28% in L-NMMA-infused rats compared with D-NMMA. In conclusion,
      ICV administration of L-NMMA causes hyperglycemia via the induction of defects in
      insulin secretion and insulin action, thus recapitulating abnormalities observed
      in type 2 diabetes. The data suggest the novel concept that central NOS-dependent
      pathways may control peripheral insulin action and secretion. This control is not
      likely to be mediated via adrenergic mechanisms and could occur via
      nonadrenergic, noncholinergic nitrergic neural and/or endocrine pathways. These
      data support previously published data suggesting that CNS mechanisms may be
      involved in the pathogenesis of some forms of insulin resistance and type 2
      diabetes independent of adiposity.

PMID- 9769334
TI  - Local overexpression of TIMP-1 prevents aortic aneurysm degeneration and rupture
      in a rat model.
AB  - Although matrix metalloproteinases (MMPs) are expressed in abundance in arterial
      aneurysms, their contribution to arterial wall degeneration, dilation, and
      rupture has not been determined. We investigated MMP function in a rat model of
      aneurysm associated with arterial dilation, elastin loss, medial invasion by
      mononuclear inflammatory cells, and MMP upregulation. Rupture was correlated with
      increased gelatinase B (MMP-9) and activated gelatinase A (MMP-2). Syngeneic rat
      smooth muscle cells retrovirally transfected with tissue inhibitor of matrix
      metalloproteinases (TIMP)-1 cDNA (LTSN) or with the vector alone as a control
      (LXSN) were seeded onto the luminal surface of the vessels. The seeding of LTSN
      cells resulted in TIMP-1 local overexpression. The seeding with LTSN cells, but
      not LXSN cells, decreased MMP-9, activated MMP-2 and 28-kD caseinase and elastase
      activity, preserved elastin in the media, and prevented aneurysmal degeneration
      and rupture. We conclude that MMP overexpression is responsible for aneurysmal
      degeneration and rupture in this rat model and that local pharmacological
      blockade might be a reasonable strategy for controlling the formation of
      aneurysms in humans.

PMID- 9769335
TI  - Augmentation of lung liquid clearance via adenovirus-mediated transfer of a Na,K
      ATPase beta1 subunit gene.
AB  - Previous studies have suggested that alveolar Na,K-ATPases play an important role
      in active Na+ transport and lung edema clearance. We reasoned that overexpression
      of Na,K-ATPase subunit genes could increase Na,K-ATPase function in lung
      epithelial cells and edema clearance in rat lungs. To test this hypothesis we
      produced replication deficient human type 5 adenoviruses containing cDNAs for the
      rat alpha1 and beta1 Na,K-ATPase subunits (adMRCMValpha1 and adMRCMVbeta1,
      respectively). As compared to controls, adMRCMVbeta1 increased beta1 subunit
      expression and Na,K-ATPase function by 2. 5-fold in alveolar type 2 epithelial
      cells and rat airway epithelial cell monolayers. No change in Na,K-ATPase
      function was noted after infection with adMRCMValpha1. Rat lungs infected with
      adMRCMVbeta1, but not adMRCMValpha1, had increased beta1 protein levels and lung
      liquid clearance 7 d after tracheal instillation. Alveolar epithelial
      permeability to Na+ and mannitol was mildly increased in animals infected with
      adMRCMVbeta1 and a similar Escherichia coli lacZ-expressing virus. Our data
      shows, for the first time, that transfer of the beta1 Na,K-ATPase subunit gene
      augments Na,K-ATPase function in epithelial cells and liquid clearance in rat
      lungs. Conceivably, overexpression of Na,K-ATPases could be used as a strategy to
      augment lung liquid clearance in patients with pulmonary edema.

PMID- 9769337
TI  - Transgenic expression of replication-restricted enteroviral genomes in heart
      muscle induces defective excitation-contraction coupling and dilated
      cardiomyopathy.
AB  - Numerous studies have implicated Coxsackievirus in acute and chronic heart
      failure. Although enteroviral nucleic acids have been detected in selected
      patients with dilated cardiomyopathy, the significance of such persistent nucleic
      acids is unknown. To investigate the mechanisms by which restricted viral
      replication with low level expression of Coxsackieviral proteins may be able to
      induce cardiomyopathy, we generated transgenic mice which express a replication
      restricted full-length Coxsackievirus B3 (CVB3) cDNA mutant (CVB3DeltaVP0) in the
      heart driven by the cardiac myocyte-specific myosin light chain-2v (MLC-2v)
      promoter. CVB3DeltaVP0 was generated by mutating infectious CVB3 cDNA at the
      VP4/VP2 autocatalytic cleavage site from Asn-Ser to Lys-Ala. Cardiac-specific
      expression of this cDNA leads to synthesis of positive- and negative-strand viral
      RNA in the heart without formation of infectious viral progeny. Histopathologic
      analysis of transgenic hearts revealed typical morphologic features of myocardial
      interstitial fibrosis and in some cases degeneration of myocytes, thus resembling
      dilated cardiomyopathy in humans. There was also an increase in ventricular
      atrial natriuretic factor mRNA levels, demonstrating activation of the embryonic
      program of gene expression typical of ventricular hypertrophy and failure.
      Echocardiographic analysis demonstrated the presence of left ventricular dilation
      and decreased systolic function in the transgenic mice compared with wild-type
      littermates, evidenced by increased ventricular end-diastolic and end-systolic
      dimensions and decreased fractional shortening. Analysis of isolated myocytes
      from transgenic mice demonstrate that there is defective excitation-contraction
      coupling and a decrease in the magnitude of isolated cell shortening. These data
      demonstrate that restricted replication of enteroviral genomes in the heart can
      induce dilated cardiomyopathy with excitation-contraction coupling abnormalities
      similar to pressure overload models of dilated cardiomyopathy.

PMID- 9769339
TI  - Localized MR spectroscopy: basic principles.
AB  - Radiologic techniques such as positron-emission tomography and single-photon
      emission tomography have been used for many years to determine metabolic changes
      in disease processes. Because of increased radiation exposure, these techniques
      are normally not used to perform extended serial studies to monitor disease
      processes. This article discusses the basics of MR spectroscopy, various
      techniques, and terminology used in clinical MR spectroscopy.

PMID- 9769336
TI  - Apoptosis mediated by Fas but not tumor necrosis factor receptor 1 prevents
      chronic disease in mice infected with murine cytomegalovirus.
AB  - The role of Fas- and TNF-receptor 1 (TNF-R1)-mediated apoptosis in the clearance
      of virally infected cells and in the regulation of the immune response was
      analyzed after murine cytomegalovirus (MCMV) infection of C57BL/6 (B6)-+/+ mice,
      Fas-mutant B6-lpr/lpr mice, TNF-R1 knockout B6-tnfr0/0 mice, and double-deficient
      B6-tnfr0/0 lpr/lpr mice. There was approximately equivalent clearance of MCMV in
      B6-+/+, B6-tnfr0/0, and B6-lpr/lpr mice, and by day 28 no infectious virus could
      be detected in the liver, kidney, lung, or peritoneal exudate. However, delayed
      virus clearance was observed in B6-tnfr0/0 lpr/lpr mice. An acute inflammatory
      response occurred in the liver, lung, and kidney of all mice, which was most
      severe 7 d after MCMV infection, but resolved by day 28 in B6-+/+ and B6-tnfr0/0
      mice, but not in B6-lpr/lpr or B6-tnfr0/0 lpr/lpr mice. These results indicate
      that apoptosis mediated by either Fas or TNF-R1 is sufficient for rapid clearance
      of the virus. However, apoptosis induced by Fas, but not TNF-R1, is required for
      the downmodulation of the immune response to the virus and prevention of a
      chronic inflammatory reaction.

PMID- 9769340
TI  - Proton MR spectroscopy of common brain tumors.
AB  - Proton MR spectroscopy allows differentiation of normal tissues from pathologic
      ones. There is now evidence that this technique may be able to distinguish
      different histological grades of tumors. The proton MR spectroscopic changes due
      to treatment of brain tumors is discussed in this article.

PMID- 9769338
TI  - Serum from patients with type 2 diabetes with neuropathy induces complement
      independent, calcium-dependent apoptosis in cultured neuronal cells.
AB  - We hypothesized that sera from type 2 diabetic patients with neuropathy contains
      an autoimmune immunoglobulin that promotes complement-independent, calcium
      dependent apoptosis in neuronal cell lines. Neuronal cells were cultured in the
      presence of complement-inactivated sera obtained from patients with type 2
      diabetes with and without neuropathy and healthy adult control patients. Serum
      from diabetic patients with neuropathy was associated with a significantly
      greater induction of apoptosis, compared to serum from diabetic patients without
      neuropathy and controls. In the presence of calcium channel antagonists,
      induction of apoptosis was reduced by approximately 50%. Pretreatment of neuronal
      cells with serum from diabetic patients with neuropathy was associated with a
      significant increase in elevated K+-evoked cytosolic calcium concentration. Serum
      induced enhancement in cytosolic calcium and calcium current density was blocked
      by treatment with trypsin and filtration of the serum using a 100,000-kd
      molecular weight filter. Treatment with an anti-human IgG antibody was associated
      with intense fluorescence on the surface of neuronal cells exposed to sera from
      patients with type 2 diabetes mellitus with neuropathy. We conclude that sera
      from type 2 diabetic patients with neuropathy contains an autoimmune
      immunoglobulin that induces complement-independent, calcium-dependent apoptosis
      in neuronal cells.

PMID- 9769341
TI  - Proton MR spectroscopy of pediatric brain tumors.
AB  - Primary central nervous system tumors are the most common solid tumors in
      children. Their overall frequency is second only to that of leukemia. Many brain
      tumors in children are relatively benign and can be successfully treated with
      surgery or radiation therapy, but progress in treating the malignant forms of
      these neoplasms lags behind that for leukemias and other solid tumors. This
      article discusses how MR spectroscopy is used to manage the individualized
      treatment of children with brain tumors.

PMID- 9769342
TI  - Proton MR spectroscopy of pediatric brain metabolic disorders.
AB  - Brain metabolic disorders are a major cause of mortality and morbidity in
      children. Proton MR spectroscopy is a sensitive diagnostic modality for these
      diseases. The abnormalities in metabolite levels revealed by MR spectroscopy
      provide specific information in a wide range of metabolic disturbances.
      Continuing MR imaging and MR spectroscopy yields maximum diagnostic information
      in an MR examination.

PMID- 9769343
TI  - In vivo MR spectroscopy of human dementia.
AB  - Nuclear MR spectroscopy in low and medium magnetic fields yields well-resolved
      natural abundance proton and decoupled phosphorus spectra from small (1-10 mL)
      volumes of brain in vivo in minutes. With this tool, neurochemical research has
      advanced through identification and noninvasve assay of a specific neuronal
      cf2Ncf1-acetylaspartate, glial (cf2myocf1-inositol)-markers, energetics and
      osmolutes, and neurotransmitters (glutamate, GABA). From these simple
      measurements, several dozen disease states are recognized, including birth
      injury, and white matter and Alzheimer disease. Together, these tools are having
      a major impact on neuroscience and clinical medicine.

PMID- 9769344
TI  - Functional MR spectroscopy of the brain.
AB  - Functional MR spectroscopy is a technique for measuring brain activation that is
      based on metabolic changes in MR spectroscopy-detectable metabolites. This
      article covers functional MR spectroscopy applications in visual stimulation,
      auditory stimulation, language activation, cerebral metabolic rate, water MR
      spectroscopy, and in psychiatric disorders. Functional MR spectroscopy offers the
      ability to measure changes in the brain during neuronal activation that may be a
      more direct measure of cellular activation than functional magnetic resonance
      imaging. MR spectroscopy-detectable chemicals that are currently of greatest
      interest for measuring brain activation are also discussed.

PMID- 9769345
TI  - In vitro 1H MR spectroscopy of squamous cell carcinoma of the extracranial head
      and neck.
AB  - Squamous cell carcinoma (SCC) is the most common malignancy of the upper
      aerodigestive tract. Investigations have been focused on the use of proton (1H)
      MR spectroscopy for evaluating diseases of the extracranial head and neck. This
      article summarizes in vitro investigations that have been performed to evaluate
      1H MR spectroscopy of SCC of the upper aerodigestive tract.

PMID- 9769346
TI  - Aspects of proton MR spectroscopy in the seizure patient.
AB  - Seizures, especially epileptic seizures, are among the most common neurologic
      symptoms. They may occur as a result of fever, hypoglycemia, or acute central
      nervous system infections. This article discusses how MR imaging and MR
      spectroscopy contribute to the management of the epileptic patient.

PMID- 9769347
TI  - Proton MR spectroscopy in inflammatory and infectious brain disorders.
AB  - This article reviews the proton MR spectroscopy literature regarding brain
      infarction and inflammatory diseases. We examine the salient findings reported
      for bacterial abscesses, intracranial tuberculomas, Creutzfeldt-Jakob disease,
      herpes simplex encephalitis and HIV. These processes demonstrate specific
      metabolic profiles which may be useful in differential diagnosis. The results
      reported in the literature support the view that MR spectroscopy can be employed
      in longitudinal studies to monitor the response to therapy and therefore may lead
      to individual optimized treatment effectiveness.

PMID- 9769348
TI  - Proton MR spectroscopy in ischemic stroke and other vascular disorders.
AB  - Proton MR spectroscopy has greatly enhanced our understanding of the in vivo
      pathophysiology of ischemic cerebrovascular disease. This article focuses on 1H
      MR spectrum changes in the setting of cerebral ischemia and infarction and shows
      how proton spectroscopy has improved our understanding of these disease
      processes. The role of 1H MR spectroscopy in cerebral ischemia without
      infarction, hypoxia-ischemic encephalopathy, and vascular dementia are also
      reviewed.

PMID- 9769349
TI  - Proton MR spectroscopy in psychiatric and neurodevelopmental childhood disorders:
      early experience.
AB  - Variations in brain morphology are increasingly being found in patients with
      psychiatric disorders. There is early evidence that some metabolic abnormalities
      may also be present in these patients. In many patients with psychiatric
      disorders, the diagnosis is not straight forward and may be confounded by co
      morbid processes. Establishing the correct diagnosis is important as it leads to
      institution of appropriate therapies. Descriptions of the authors early
      experience using proton MR spectroscopy in the evaluation of children with
      bipolar affective disorder, attention deficit hyperactivity disorder,
      neurodevelopmental abnormalities in patients with neurofibromatosis type 1, and
      the effects of certain types of treatment used for these disorders are discussed.

PMID- 9769350
TI  - Osteoporosis in women.
AB  - Osteoporosis affects over 40 million women each year. This insidious disease is
      most common to women, especially over the age of 50. Osteoporosis leads to an
      increased risk of fracture, subsequently impacting morbidity and mortality and
      the quality of life in affected women. The nurse is an integral partner by
      helping women confront this condition through risk identification, preventive
      techniques, new treatment modalities, education, and follow-up.

PMID- 9769351
TI  - Common orthopedic problems of the newborn.
AB  - Newborn orthopedic problems are cause for major concern, both economically and
      emotionally, for the family. Dysplasia of the hip and abnormal feet can be
      successfully diagnosed and treated with proper assessment and early recognition.
      This article reviews the orthopedic examination for the newborn infant, discusses
      the major orthopedic problems encountered in the neonate, and provides guidelines
      that will impact the course of the condition for both the patient and family for
      those professionals working in orthopedics.

PMID- 9769352
TI  - Rheumatoid arthritis: a case study.
AB  - Rheumatoid arthritis (RA) is a chronic, systemic, progressively deteriorating,
      connective tissue disease characterized by inflammation of the synovial membrane
      of the joints, pain, immobility, and fatigue. Exacerbations of RA are frequently
      associated with periods of physical and/or emotional stress. It is estimated that
      1 in every 100 persons throughout the world suffers from RA. In the United
      States, women have 2 to 3 times the incidence rate of men, with no significant
      radical differences noted between Caucasians and African-Americans. In this
      article a case study format is used to provide information pertaining to the
      diagnosis and treatment of the adult RA patient.

PMID- 9769353
TI  - Pregnancy in women with spinal cord injuries.
AB  - Most women with spinal cord injuries (SCI) resume normal reproductive function,
      can have sexual relationships, and become pregnant. Pregnancy is not
      contraindicated in women with SCI, but pregnant women with acute or chronic SCI
      pose unique challenges for perinatal health care providers. The normal
      physiologic changes of pregnancy may predispose women with SCI to potentially
      life-threatening complications, including autonomic hyperreflexia,
      pyelonephritis, respiratory insufficiency, thrombophlebitis, and unattended
      delivery of the infant. This article reviews the effect of SCI on female
      reproduction, pregnancy, and labor, and summarizes the treatment of the pregnant
      woman with a spinal cord injury.

PMID- 9769354
TI  - Considerations for the orthopedic nurse in diagnosis and treatment of adolescent
      sports injuries.
AB  - Injured adolescent athletes are challenging clients for the primary practitioner.
      Their unique physiological and psychological attributes dictate changes in
      traditional orthopedic practice and call for a holistic patient focus to address
      their varied needs. Understanding of common athletic injuries will effectively
      guide the practitioner's clinical evaluation and assist in recognizing those
      patients requiring more complex orthopedic diagnosis and care.

PMID- 9769355
TI  - Preventing amputations in the diabetic population.
AB  - More than 50% of all lower extremity amputations occur in patients with diabetes.
      This phenomenon is largely preventable through risk factor reduction and proper
      foot care education. In cases where lower extremity injury or infection are
      present prompt and aggressive care can preserve the limb. New techniques for
      revascularization to ulcerated areas of the foot are promoting wound healing and
      improving long term outcomes.

PMID- 9769356
TI  - Physical assessment of the musculoskeletal system.
AB  - The musculoskeletal examination may vary widely in its objectives and content. It
      may be part of a comprehensive physical examination, or may be directed toward
      evaluation of problems localized to a specific area. The basic screening
      examination, medical interview and history will be considered in this article, as
      well as some resources for reviewing the more focused evaluation of particular
      problem areas.

PMID- 9769357
TI  - Fibromyalgia syndrome.
AB  - Fibromyalgia syndrome (FMS) is a more common a condition than previously
      estimated. The most recent estimates are that 3 to 6 million patients have been
      diagnosed with FMS. The ACR criteria, established in 1990, provide the primary
      care provider with definitive subjective and objective findings that have shown
      to be 88% accurate in their ability to diagnose patients with the syndrome. There
      is no cure for FMS. It is a chronic condition, but patients quality of life can
      be improved when fatigue and pain are reduced. The institution of a plan that is
      developed collaboratively by the patient and the provider is the essence of
      successful symptom management. The hallmarks of the management plan include:
      improving the quality of sleep through the judicious use of medications that
      boost the body's level of serotonin (therefore reducing fatigue), and reducing
      pain through complimentary modalities such as exercise, physical therapy,
      relaxation techniques, massage, and biofeedback.

PMID- 9769358
TI  - Prevention of infection in the orthopedic surgery patient.
AB  - A surgical site infection in an orthopedic surgery is a dreaded and often
      catastrophic complication. This article provides an overview of the incidence,
      pathogenesis, financial impact, as well as a discussion of patient and operation
      related risk factors for orthopedic surgical site infections. The reader is
      provided insight into infection control interventions intended to minimize
      surgical site infections in orthopedic patients. Some of these practices are
      evidence-based and others exist only because of theoretical benefit.

PMID- 9769359
TI  - Laboratory tests and diagnostic procedures in orthopedic nursing practice.
AB  - Orthopedic nurses need to know the clinical significance of their clients'
      laboratory test because critical analysis of the results is essential for
      clinical decision making. Nurses are expected to use the results in their own
      plan of care. Client education about diagnostic tests is also an important role
      of the orthopedic nurse.

PMID- 9769360
TI  - Companion animals: social support for orthopedic clients.
AB  - Various definitions, conceptualizations, and measurements of social support exist
      in literature. Consistently among these variations, the focus is on people.
      Companion animals are not included; however, reviews of both social support
      literature and human-animal bond literature shows that the two share a number of
      common functions. Using two case studies, the author demonstrates that the social
      support of companion animals is a legitimate and relevant source of support for
      persons with orthopedic disorders.

PMID- 9769361
TI  - Biomedical and feminist perspectives on low back pain during pregnancy.
AB  - Low back pain (LBP) is a common symptom seen by nurses who provide care for
      people with orthopedic problems. Many women experience their first episodes of
      LBP during pregnancy. Two perspectives for exploring LBP, biomedical and
      feminist, are described in this article. A combination of these perspectives
      might best serve women. Also, examples from a research project that used both
      perspectives is provided.

PMID- 9769362
TI  - Chromium-induced genotoxicity and apoptosis: relationship to chromium
      carcinogenesis (review).
AB  - The adverse health effects linked with chromium (Cr) exposure, the role of
      solubility and chemical speciation of Cr compounds, and the diverse cellular and
      molecular effects of Cr make the study of Cr carcinogenesis and toxicology very
      interesting and complex. Certain Cr compounds are prominent metal carcinogens in
      both occupational and environmental settings. Inhaled particulate forms of
      hexavalent Cr [Cr(VI)] cause lung cancer as well as lung toxicity. Some of the
      important factors in determining the biological outcome of Cr exposure include
      the bioavailability, chemical speciation and solubility of Cr compounds,
      intracellular reduction, and interaction of Cr with DNA. The stable oxidation
      states of Cr found in nature are Cr(III) and Cr(VI). Cr(III) is unable to enter
      cells but Cr(VI) enters into cells through membrane anionic transporters.
      Intracellular Cr(VI) is metabolically reduced to the ultimate Cr(III). Cr(VI)
      does not react with macromolecules such as DNA, RNA, proteins and lipids.
      However, both Cr(III) and the reductional intermediate Cr(V) are capable of co
      ordinate covalent interactions with macromolecules. At the genomic level, Cr
      genotoxicity manifests as gene mutations, several types of DNA lesions and
      inhibition of macromolecular synthesis. At the cellular level, Cr exposure may
      lead to cell cycle arrest, apoptosis, premature terminal growth arrest, or
      neoplastic transformation. Cr-induced DNA-DNA interstrand crosslinks (DDC), the
      tumor suppressor gene p53 and oxidative processes are some of the major factors
      that may play a significant role in determining the cellular outcome in response
      to Cr exposure. We have utilized cellular, molecular, pharmacological, and
      genetic approaches to understand the interrelationship between Cr-induced
      genotoxicity, apoptosis and carcinogenesis. This review is based on the results
      and inferences of this research. We hope this review will clarify existing
      concepts and also introduce novel perspectives in chromium carcinogenesis
      research.

PMID- 9769363
TI  - Perturbation of rodent hepatocyte growth control by nongenotoxic
      hepatocarcinogens: mechanisms and lack of relevance for human health (review).
AB  - During the development of new industrial and pharmaceutical chemicals, it is
      necessary to determine whether they are potential carcinogens. However, there are
      no short-term tests available for nongenotoxic carcinogens that do not damage DNA
      yet cause tumours in rodent bioassays. The peroxisome proliferators (PPs)
      constitute a diverse class of nongenotoxic carcinogens that include chemicals of
      therapeutic, industrial and environmental importance such as hypolipidaemic
      fibrate drugs, clingwrap/medical tubing plasticizers and certain pesticides and
      solvents. PPs induce DNA synthesis and suppress apoptosis in rat and mouse
      hepatocytes, leading to tumour formation. In addition to altering hepatocyte
      growth and survival, PPs cause peroxisome proliferation and the induction of
      enzymes of the beta-oxidation pathway. PPs mediate their biological responses in
      rodents via activation of the nuclear hormone receptor PPARalpha (peroxisome
      proliferator activated receptor alpha) which regulates expression of the genes
      associated with response to PPs. The mechanisms through which normally quiescent
      hepatocytes are recruited into the cell cycle currently remain obscure. However,
      it is probable that expression of hepatic cytokines by hepatic macrophages
      (Kupffer cells) may be involved. In common with other classes of nongenotoxic
      carcinogen, there are remarkable species differences in response to PPs; humans
      respond to the fibrate hypolipidaemic PPs via a reduction in serum cholesterol
      but appear refractory to the adverse effects of PPs such as hepatic peroxisome
      proliferation, DNA synthesis and tumour formation. The molecular basis of the
      observed species differences in response to PPs is unclear at present, but recent
      data support a quantitative hypothesis wherein PPARalpha expression levels are
      sufficient in humans to mediate hypolipidaemia, but too low for transcriptional
      regulation of the full battery of genes associated with the adverse effects seen
      in rodents such as peroxisome proliferation, liver enlargement and tumours. A
      more detailed understanding of the mechanisms through which these chemicals cause
      tumours in rodents and how humans may differ will assist in extrapolation of
      rodent data to human risk assessment.

PMID- 9769364
TI  - Chromosome 10 alterations in prostate adenocarcinoma (review).
AB  - Inactivations of tumor suppressor genes are the most common genetic alterations
      in prostate adenocarcinoma. Such inactivations are frequently accompanied by loss
      of portions of the chromosome on which the tumor suppressor gene resides. Loss of
      portions of both 10p and 10q have been identified in a significant percentage of
      prostate carcinomas, as well as other malignant neoplasms, and such losses are
      associated with advanced clinical stage and aggressive behavior in these
      neoplasms. The PTEN tumor suppressor gene has recently been identified as an
      important tumor suppressor gene at 10q23. This gene encodes a dual specificity
      protein phosphatase which interacts with and controls the tyrosine
      phosphorylation of focal adhesion kinase (FAK), a key regulator of signal
      transduction via focal adhesions. Such focal adhesions are the site at which
      integrins cluster following interactions with extracellular matrix ligands and
      interact with both cytoskeletal proteins and signal transduction molecules to
      effect key processes such as cell migration, spreading and proliferation. The
      PTEN gene is inactivated in a significant proportion of prostate carcinomas,
      particularly metastatic prostate cancers. There is also evidence from studies of
      loss of heterozygosity that at least one additional tumor suppressor gene for
      prostate cancer is present on the distal portion of 10q. Similarly, both
      functional studies and direct analysis of human tumors strongly support the idea
      that at least one, and possibly two, tumor suppressor genes for prostate cancer
      are present on 10p. Given that inactivations of tumor suppressor genes on
      chromosome 10 are associated with advanced clinical stage in prostate cancer
      these genes are attractive candidates both as prognostic markers and as potential
      targets for therapeutic intervention.

PMID- 9769365
TI  - Conservation treatment intensified with tamoxifen and CAF chemotherapy for
      subareolar breast cancers.
AB  - Formerly, patients with subareolar breast cancers have not been good candidates
      for breast-conservation treatment (BCT) in Japan. However, recently it was
      reported that patients with subareolar cancers were good candidates for this
      treatment. In order to improve both cosmetic results and survival rates, we
      performed BCT for 27 patients with subareolar breast cancers following pre
      operative CAF chemotherapy and tamoxifen administration. From August 1989 to June
      1998, we performed BCT for 200 out of 206 patients who visited our hospital with
      the desire of breast-conservation. Of these patients, 27 presented with tumors
      within 2 cm of the nipple areolar complex. For 26 of these 27 patients, breast
      conserving surgery was performed following two to four times of CAF chemotherapy,
      and another one patient did not undertake any surgical resection. Following the
      surgery, patients were treated with radiation therapy to the intact breast and
      ipsilateral axilla to a total dose of 4,400 cGy with electron conedown to a total
      dose of 5,300 cGy. Their primary tumors were at T4bN0 in 1 case, T2N1b in 5
      cases, T2N0 in 18 cases, and T1cN0 in 3 cases. Tamoxifen was administered to all
      the patients. CAF chemotherapy was performed six times for stage I patients, and
      eight times for stage II patients in total. For one patient with direct tumor
      invasion to the nipple, intraarterial infusion chemotherapy was performed
      following radiation therapy and CAF chemotherapy, without any surgical resection.
      For another 26 patients, breast-conserving surgery was performed, and 5 of them
      underwent lumpectomy under local anesthesia on an outpatient basis. For these 26
      patients, the microscopic surgical margin was positive for 8 patients, close for
      6 patients, negative for 10 patients, and unknown for 2 patients. All patients
      are alive with no evidence of disease after a follow-up of approximately 47
      months on average, and all of their cosmetic results are estimated as excellent
      or good. It is concluded that BCT intensified with preoperative CAF chemotherapy
      and tamoxifen for subareolar breast cancers is a satisfying treatment modality in
      terms of both cosmetic results and survival rates.

PMID- 9769366
TI  - Tumor angiogenesis as an independent prognostic indicator in human papillary
      thyroid carcinoma.
AB  - Angiogenesis has been determined to play a very important role in either the
      growth of solid tumors or their recurrence in distant organs. Microvessels
      stained immunohistochemically for the factor VIII-related antigen were counted in
      one hundred patients with papillary thyroid carcinoma in order to clarify the
      association of tumor angiogenesis with the prognosis of the disease. The mean
      microvessel count (MVC) was significantly higher in tumors with distant
      recurrence than those without recurrence. Disease-free survival of patients with
      a high MVC (>/= 23) was significantly worse than that of patients with a low MVC
      (</= 22), as well as the overall survival. In multivariate analysis, the MVC was
      most strongly correlated with disease-free survival, and was independent of other
      prognostic factors. In conclusion, the MVC is a potent prognostic indicator in
      papillary thyroid carcinoma.

PMID- 9769367
TI  - Cysteine proteinases and their endogenous inhibitors: target proteins for
      prognosis, diagnosis and therapy in cancer (review).
AB  - Lysosomal cysteine proteinases, the cathepsins (Cats) belong to the papain family
      of proteinases, sharing a similar protein structure and mechanism of action.
      Subtle structural differences between these enzymes give rise to important
      variations in substrate specificity and specificity of inhibition by their
      endogenous inhibitors, the cystatins, stefins and kininogens under physiological
      and pathological conditions. Alterations in their expression, processing and
      localization have been observed at various levels in malignant human tumor tissue
      compared to normal and benign tissue counterparts. We have proposed that an
      imbalance between cathepsins and cystatins, associated with metastatic tumor cell
      phenotype, may facilitate tumor cell invasion and metastasis. The results of
      clinical investigations on cysteine cathepsins and their endogenous inhibitors in
      human breast, lung, brain and head and neck tumors, as well as in body fluids of
      ovarian, uterine, melanoma and colorectal carcinoma bearing patients, have shown
      that these molecules are highly predictive for the length of survival and may be
      used for assessment of risk of relapse and death for cancer patients. Their
      application for diagnosis, follow-up and the anticancer therapy has also been
      proposed.

PMID- 9769368
TI  - Antineoplaston treatment for advanced hepatocellular carcinoma.
AB  - Antineoplaston A10 injection (antineoplaston A10 I) exhibited cystostatic growth
      inhibition of human hepatocellular carcinoma (HCC) cells in vitro and showed
      minimum adverse effects in a phase I clinical trial. Advanced HCC is hard to
      control because the potent anticancer drugs or embolizations easily induce
      hepatic failure. We review herein 2 cases of advanced HCC treated with
      antineoplaston A10 I. Both cases showed interesting responses to antineoplaston
      A10 I. One showed massive coagulation necrosis of tumors after intra-arterial
      infusion of antineoplaston A10 I and the other showed resolution of portal vein
      tumor thrombosis with systemic infusion of antineoplaston A10 I. The usefulness
      of anti-neoplaston A10 I in terminal staged HCC is discussed.

PMID- 9769369
TI  - Local resection after breast-conserving therapy.
AB  - We analyzed the results of local re-excision after radiation therapy on seven
      patients with positive surgical margins at the initial breast-conserving surgery.
      The age of the patients ranged from 30 to 55 years, and the tumor sizes from 1.1
      to 4.7 cm. Both estrogen receptor and progesterone receptor status were positive
      in two patients, negative in four, and unknown in one. Pathological examination
      revealed residual carcinoma in one (14.3%) of seven patients. The
      immunohistochemical results of the initial specimen were estrogen receptor
      positive, c-erbB-2-positive, and Bax-negative. We performed local re-excision
      after radiation therapy and found only one incidence of residual carcinoma in the
      conserved breast.

PMID- 9769370
TI  - No susceptibility of colon tissue implanted into the glandular stomach of rats to
      N-nitroso-N-methylurea carcinogenesis.
AB  - The present study was undertaken to determine the response of colonic mucosa
      implanted into the stomach fundus in 6-week-old male F344 rats to oral
      administration of N-nitroso-N-methylurea (MNU). In graft + MNU, 15% animals had
      tumors in the implanted colon tissue whereas a 26% incidence of gastric tumors
      was observed for the pyloric mucosa. In MNU alone, 30% of rats demonstrated
      gastric tumors. In graft alone 10% of tumors were observed in the grafted site
      but none in the pylorus. Thus while graft tissue may intrinsically have an
      elevated risk of tumor development, no susceptibility to MNU was observed in the
      present study.

PMID- 9769371
TI  - Induction of ovarian tumors by heavy ion irradiation in B6C3F1 mice.
AB  - Six-week-old B6C3F1 mice were exposed to 0.439 Gy heavy ion irradiation as a 290
      MeV/u carbon-ion beam (LET 10 keV/micron) at 2 cm from the upper proximal point
      of a spread Bragg beam and autopsied 13.5 months after the irradiation. In males
      total tumor incidences, mainly liver tumors, were 37.0% in irradiated group and
      25.0% in control (P>0.05). In females the total tumor incidences were 32.3%,
      mainly ovarian tumors, in the irradiated group and 0% in the controls. These
      results indicate that heavy ion irradiation induces ovarian tumors in females but
      does not target any organ in males.

PMID- 9769372
TI  - In vitro cytotoxicity of paclitaxel-transferrin conjugate on H69 cells.
AB  - Transferrin is a serum glycoprotein involved in iron transport. Transferrin acts
      also in cell growth regulation through membrane receptors. The number of
      transferrin receptors is increased in tumor and other rapidly dividing cells.
      This renders transferrin suitable for use in cytotoxic drugs targetting tumor
      cells. Paclitaxel was derivatized on 2' carbon and coupled with trasferrin using
      glutaraldehyde. The cytotoxicity of the conjugate was evaluated on small cell
      carcinoma of the lung cell line (H69). As compared to paclitaxel, the conjugate
      exhibited a slight decrease in cytotoxicity.

PMID- 9769373
TI  - Relationship of polyamine metabolism to degree of malignancy of human
      hepatocellular carcinoma.
AB  - We investigated polyamine metabolism in hepatocellular carcinoma (HCC) with
      respect to tumor volume doubling time, degree of differentiation, and prevalence
      of portal invasion and intrahepatic metastasis. Ornithine decarboxylase (ODC)
      activity and the spermidine/spermine ratio were correlated with tumor volume
      doubling time. ODC activity was higher in moderately and poorly differentiated
      HCC than in well-differentiated HCC. The prevalence of portal invasion and
      intrehapatic metastasis was higher in patients with high ODC activities. We
      conclude that polyamine metabolism in HCC estimates the degree of malignancy.

PMID- 9769374
TI  - Expression of cytokines enhancing the osteoclast activity, and parathyroid
      hormone-related protein in prostatic cancers before and after endocrine therapy:
      an immunohistochemical study.
AB  - Cytokines, interleukin (IL)-1alpha, IL-1beta, IL-3, IL-6, macrophage colony
      stimulating factor (M-CSF) and tumor necrosis factor-alpha (TNF-alpha) as well as
      parathyroid hormone-related protein (PTHrP) have been shown to enhance the
      osteoclast activity. To investigate mechanisms of the development of bone
      metastasis of prostatic cancers, expression of these cytokines and PTHrP was
      examined immunohistochemically in prostatic cancers of patients administered no
      prior therapy or endocrine therapy. All cytokines and PTHrP were stained in the
      cytoplasm of the epithelium of non-cancerous prostatic glands, and IL-3 and IL-6
      were stained in the cytoplasm of smooth muscle cells besides epithelial cells of
      non-cancerous prostatic glands. Incidences of positivity of staining in prostate
      cancers of patients administered no prior therapy were 100% for IL-1alpha, IL
      1beta, IL-6, M-CSF and TNF-alpha, 20% for IL-3, and 80% for PTHrP. Incidence of
      prostatic cancers stained positively for IL-1alpha and IL-1beta decreased
      significantly in patients administered endocrine therapy, but those for IL-3, IL
      6, M-CSF, TNF-alpha and PTHrP did not change significantly. The present results
      suggest that prostatic cancers produce various cytokines, IL-1alpha, IL-1beta, IL
      3, IL-6, M-CSF and TNF-alpha, as well as PTHrP, and that expression of these
      cytokines and PTHrP except IL-1alpha and IL-1beta is not under androgen control.
      Cytokines and PTHrP produced by prostatic cancers may play a role in the
      development of bone metastasis of prostatic cancers.

PMID- 9769375
TI  - Potentiation by 2-deoxy-D-glucose tetraacetate of the cytostatic action of alpha
      difluoromethylornithine in tumoral insulin-producing cells.
AB  - Insulin-producing tumoral cells of the RINm5F line were cultured for 8 to 96 h in
      the absence or presence of 2-deoxy-D-glucose tetraacetate (0.01 mM to 1.0 mM)
      and/or a-difluoromethylornithine (also 0.01 mM to 1.0 mM). The ester of the
      glucose analog potentiated the inhibitory action of the ornithine decarboxylase
      inhibitor. For instance, when both agents were tested in combination at a
      concentration of 0.01 mM each, the generation of formazan from 3-[4,5
      dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium was decreased, within 2 days, to
      23.2+/- 6.1% of its paired control value, whilst neither the ester of 2-deoxy-D
      glucose nor the ornithine analog exerted any significant effect upon cell growth
      when used separately at the same low concentration and over the same length of
      culture. These findings suggest that 2-deoxy-D-glucose tetraacetate could be used
      to sensitize tumoral cells to the cytostatic action of established
      chemotherapeutic agents in the treatment of neoplastic diseases.

PMID- 9769376
TI  - Mass screening for neuroblastoma by HPLC and by non-HPLC: a review.
AB  - There have been a number of contradictory views concerning the efficacy of mass
      screening for neuroblastoma. Three Japanese and one cohort study from Quebec, and
      three Japanese cross-sectional studies were reviewed. The four cohort studies
      revealed that mass screening using high performance liquid chromatography (HPLC)
      reduced the incidence of this disease by about half in children aged from 1 to 4
      years while little reduction was noted in screening utilizing non-HPLC methods.
      There is a large difference in the efficacy of mass screening depending on the
      method used. In the three cross-sectional studies, there was no discrimination
      between screened and unscreened cases, or between subjects screened by HPLC and
      non-HPLC methods. The percentage of children in the cross-sectional studies
      screened by HPLC was low. Cross-sectional studies seem inappropriate in assessing
      the effectiveness of current HPLC mass screening.

PMID- 9769377
TI  - Thin section computed tomography in the prone position for detection of axillary
      lymph node metastases in breast cancer.
AB  - Presence or absence of lymph node metastases is the most accurate prognostic
      indicator in breast cancer. Clinical examination is unreliable in detecting
      involved nodes. Formerly, CT (computed tomography) was concluded to be an
      unreliable predictor of axillary lymph node involvement, primarily because of its
      low negative predictive value. In our institute, thin section CT (TS-CT) in the
      prone position was performed in patients with breast cancer to improve the
      predictability of axillary lymph node involvement. Pre-operative TS-CT
      examination of the axilla and breast was performed in 71 women with breast
      cancer. The sensitivity for involved nodes was 93.8%, the specificity 82.1%, and
      the accuracy 87. 3%. Based on these results, we concluded that TS-CT is an
      accurate predictor of axillary lymph node involvement. However, the upper limit
      of accuracy was approximately 85% for the imaging diagnoses, mainly because of
      the existance of micrometastases.

PMID- 9769378
TI  - Genetic diagnostic test of hepatocellular carcinoma by telomerase catalytic
      subunit mRNA.
AB  - This study investigated the relationship between telomerase activity and telomere
      length and between telomerase reverse transcriptase (hTERT) mRNA and telomere
      length. Both cancerous and non-cancerous tissues were studied in individuals with
      hepatic carcinoma. In this study, the telomere length in HCC livers had a wide
      range, no clear significant correlation was found between hTERT mRNA and telomere
      length. Telomerase activity was more strongly correlated with hTERT mRNA than
      with telomere length. The correlation between hTERT mRNA and telomerase activity
      shown here indicates that hTERT mRNA has potential for cancer diagnosis.

PMID- 9769379
TI  - Increased cancer incidence in physicians, dentists, and health care workers.
AB  - Some earlier reports have indicated increased incidence or mortality of specific
      tumor types in various health care professions. In this study we have evaluated
      cancer incidence in physicians, dentists, and other health care workers using the
      Swedish Cancer Environment Register (CER), which was formed by record-linkage
      between the 1970 census on current occupation and Cancer Register incidence data
      in 1971-84. In all three profession categories studied an increased risk was
      found, as well for all malignant tumors combined, as for specific tumor types
      regarding the different occupations. Possible etiological factors responsible for
      these risks are discussed.

PMID- 9769380
TI  - Concentrations of vascular endothelial growth factor in the sera of gastric
      cancer patients.
AB  - VEGF (vascular endothelial growth factor) is known to play crucial roles in tumor
      angiogenesis. In 281 gastric cancer patients, aberrant increase of VEGF level was
      observed in 36 patients (12.8%). In 14 recurrent patients, 8 showed an increase
      of VEGF. The serum VEGF levels of stage IV cancer were significantly higher than
      those of stage I. The serum levels of recurrent patients were significantly
      higher than those of stage I, II and III. VEGF levels of patients with serosal
      invasion were significantly higher than those of patients without serosal
      invasion. In depth of invasion (t-factor), VEGF levels of t4 cancer were
      significantly higher than those of t1-t3. In venous infiltration of tumors, VEGF
      levels of v3 were significantly higher than v0 and v1. There was no significant
      difference with respect to H-factor and P-factor status. In eleven recurrent or
      advanced gastric cancer patients, serum VEGF was sequentially examined between
      pre- and post-chemotherapy. All of them showed a decrease of serum VEGF
      concentration after partial response by chemotherapy. The patients who had
      progressive disease after chemotherapy showed an increase of VEGF levels. Serum
      VEGF levels were closely related to the extent of gastric cancer and the response
      of chemotherapy.

PMID- 9769381
TI  - Histologically pure seminoma with elevated alpha-fetoprotein: a clinicopathologic
      study of ten cases.
AB  - Seminomas account for 50% of testicular germ-cell tumors, and more than 90% of
      these are classic seminomas. When patients with a histologically pure testicular
      seminoma show an elevated level of serum a-fetoprotein (AFP), it is generally
      assumed that an undetected focus of yolk sac tumor (YST) is present and the
      patient is managed with a treatment regimen for non-seminomatous tumor. We
      studied 10 cases of histologically pure seminoma with elevated levels of serum
      AFP in an attempt to identify any distinctive clinical, histopathologic, or
      immunohistochemical features. The patients ranged in age from 27 to 48 years
      (mean, 31 years). Eight patients had primary tumors of the testis, and two
      presented with supraclavicular and ileal tumors. The clinical stage at
      presentation varied: four tumors were stage I, four were stage II, and two were
      stage III. Serum levels of AFP were elevated in all patients at ranges of 10.4 to
      16 ng/ml (mean, 12.0 ng/ml). In all patients, the primary tumors and metastases
      when present exhibited classic seminoma histology without other germ-cell
      components. The tumor cells expressed keratin in seven cases. The pattern of
      keratin immunoreactivity ranged from focal staining in five cases to moderate
      staining in two cases. All cases were negative for AFP, and the nine cases in
      which staining for CD30 (Ki-1) was performed were also negative. All four
      patients with stage I tumors underwent the conventional therapy for pure
      seminoma, i.e., orchiectomy and subsequent radiation therapy. Five patients
      received treatment for non-seminomatous tumors, i.e., chemotherapy after
      orchiectomy. Extensive work-up failed to detect the primary tumor in one patient,
      and he was treated for a non-seminomatous tumor, undergoing chemotherapy and
      irradiation. All patients are alive and well, and none has developed evidence of
      YST at a mean follow-up of 6 years (range, 6 months to 10 years). However, one
      patient who presented with an ileal metastasis recently developed a second
      primary extragonadal mediastinal mixed germ-cell tumor with YST and embryonal
      carcinoma components and an elevated serum level of AFP (27,000 ng/ml) after a 10
      year disease-free follow-up. This study strongly suggests that minor elevations
      (</= 16 ng/ml) of AFP in patients with an otherwise pure seminoma may not
      indicate that there is a hidden focus of YST and that such patients should be
      treated with standard therapy for seminoma. Because this study includes very few
      patients, further studies are required to better understand the significance of
      borderline elevations of AFP in cases of histologically pure seminoma.

PMID- 9769382
TI  - Inhibition of breast cancer in nude mouse model by anti-angiogenesis.
AB  - The mechanism by which DL-alpha-difluoromethylornithine (DFMO) inhibits
      angiogenesis is generally thought to involve the inhibition of the rate-limiting
      enzyme, ornithine decarboxylase (ODC), leading to polyamine depletion in cells
      and the ultimate cytostatic effect on proliferating endothelial cells. Another
      mechanism for inhibiting tumor growth involves pentosan polysulfate (PPS) which
      binds heparin-binding growth factors, known to be crucial for tumor angiogenesis.
      To quantitate the combined anti-angiogenic effect of DFMO and PPS on tumors,
      blood vessels were stained using monoclonal antibodies against the platelet
      endothelial cell adhesion molecule (PECAM). When compared to untreated mice,
      DFMO/PPS-treated mice exhibited significantly lower (6-fold) blood vessel counts.
      Furthermore, mice receiving the combination drug treatment had prolonged life
      compared to untreated tumor-bearing mice, but less than normal tumor-free mice.
      The prolonged life span of drug treated tumor-bearing mice also correlated with
      reduced tumor burden in these mice. The use of single drug treatment results in
      rapid tumor growth and eventual death of tumor-bearing mice. We have demonstrated
      that there was significant difference in survival time which correlated to less
      tumor burden in treated groups of mice as compared to the controls. Inhibition of
      tumor angiogenesis by the drug combinations suggest that these compounds are anti
      angiogenic agents for potential use in clinical trial.

PMID- 9769383
TI  - Long-term cure of a malignant lymphoma of the pleural cavity treated by
      irradiation.
AB  - Malignant lymphomas arise in the pleura in association with a long-standing
      chronic tuberculous pyothorax. We report a case of a non-Hodgkin's lymphoma of
      the pleural cavity, inoperable because of local invasion into thoracic wall, who
      has survived more than 6 years without recurrence. This patient represents the
      longest reported survival after radiation therapy alone. Radiotherapy holds an
      important role in the treatment of locally advanced lymphoma of the pleural
      cavity.

PMID- 9769384
TI  - Changes in natural killer cell activity and prostaglandin E2 levels during the
      progression of diethylnitrosamine-induced hepatocarcinogenesis in Fischer 344
      rats.
AB  - The sequential changes of natural killer cell (NK) activity and prostaglandin E2
      (PGE2) during hepatocarcinogenesis induced by diethylnitrosamine (DEN) in male
      Fischer 344 rats were investigated. DEN at a concentration of 40 ppm was
      administered in drinking water for 10 weeks. At weeks 5, 10, 20 and 30, rats were
      autopsied and the development of glutathione S-transferase placental form
      positive foci (GST-P+ foci) at weeks 5 and 10 and hepatocellular tumors at weeks
      20 and 30 were examined. The labeling index of bromodeoxyuridine (BrdU) an
      indicator of DNA synthesis, was also sequentially checked. GST-P+ foci were found
      to increase with age. Hepatocellular nodules increased until week 20, but by week
      30 when the incidence of hepatocellular carcinoma was 100%, the incidence of
      nodules had decreased. BrdU positive cells also increased with age, and by week
      30 when the incidence of hepatocellular carcinoma was 100%, the number of BrdU
      positive cells had decreased. NK cell activity increased until week 10, but at
      week 20, was less than in the untreated control group. The level of PGE2
      increased until week 5, but at week 10, levels were not significantly different
      from those seen in the untreated control group. On the basis of these results, we
      concluded that NK activity is closely related to the progression of
      hepatocarcinogenesis, but PGE2 levels show no significant change.

PMID- 9769385
TI  - Telomerase activity in thyroid tumors.
AB  - We quantified telomerase activities in thyroid tumors by a telomeric-repeat
      amplification-protocol-based assay in an attempt to determine its clinical
      significance. Telomerase activity was detected in 10 of 18 (55.6%) malignant
      tumors, but in none of the four benign lesions, and the level of telomerase
      activity correlated significantly with the progression of the clinical stages.
      High activity was determined in 4 (80%) of 5 metastatic lesions in the lymph
      nodes. Five (45.5%) of 11 non-tumoral specimens from malignant cases showed
      telomerase activity, while none of the four from benign cases did. In conclusion,
      the determination of telomerase activity might be useful in determining the
      existence and progression of thyroid cancer.

PMID- 9769386
TI  - Activation of the ras genes in malignant and premalignant colorectal tumors.
AB  - The activation of ras genes has been established as one of the steps in the
      process of colon tumorigenesis. These genes are converted into active oncogenes
      by point mutations in codons 12, 13, and 61, although a more complex way has also
      been shown, through alteration of gene expression. In order to investigate the
      spectrum of ras gene mutations, we examined 78 colorectal polypoid adenomas and
      76 primary colorectal adenocarcinomas for codon 12 point mutations in K-, H- and
      N-ras, using a PCR-RFLP assay. K-ras mutations were found in 42.3% (33/78) of
      adenomas and in 36.8% (28/76) of carcinomas. Statistically significant
      association (p=0.043) was found between the frequency of K-ras mutations in mixed
      adenomas larger than 2 cm, compared to smaller mixed adenomas. On the other hand,
      adenocarcinomas harbored more frequently mutations, when indicating development
      from adenoma (p=0.016), in higher grade of differentiation (p=0.001) and in
      females with tumor located proximal to the rectosigmoid (p=0.013). No mutations
      were found in H-ras. The incidence of N-ras mutations was 1.3% in adenomas and
      adenocarcinomas (1/78 and 1/76 respectively). Based on our results, we propose
      the possibility that K-ras-dependent tumor development results in the formation
      of less aggressive neoplasms, than the process of K-ras-independent
      carcinogenesis. Our findings and other previous reports indicate that K-ras
      mutations might be a secondary stress-effect from extrinsic or intrinsic
      stimulatory factors and that these mutations are not necessarily involved in the
      malignant transformation of the cell.

PMID- 9769387
TI  - The prevalence of p53 immunoreactivity in anal canal carcinoma.
AB  - We examined the relationship between p53 expression and clinicopathologic
      parameters in anal carcinoma. p53 immunoreactivity was detected in 14/18 (77.7%)
      tumors. Significant association was found between p53 expression and depth of
      invasion. There was no significant association between p53 expression and
      histologic type, lymph node metastasis, age and prognosis. Possibly the genetic
      pathway to anal carcinoma involving p53 gene overexpression confer aggressive
      growth pattern, but it does not result in worse prognosis. The absence of
      correlation between p53 overexpression and prognosis could be explained by tumors
      negative for mutations having an excess of wild-type p53 protein.

PMID- 9769388
TI  - Interleukin 3 in the treatment of chemotherapy induced thrombocytopenia.
AB  - We enrolled 19 cancer patients (11 females, 8 males) with thrombocytopenia after
      standard dose of chemotherapy to receive IL3 10 mg/kg/day s.c. until hematologic
      recovery. Therapeutic success was obtained in 69.6% of cycles; a major response
      in 39.3% and a minor response in 30.3% of cycles. We obtained the best results in
      case of platelet count <49,000/mm3. The main toxicity was a flu-like syndrome. In
      two cycles (6%) we registered allergic episodes with flushing and lipothymia. In
      the 47% of cycles evaluable for toxicity no side effect was registered.

PMID- 9769389
TI  - Use of 5-fluorouracil, epirubicin and mitomycin C (FEM) as adjuvant therapy in
      node-positive, radically-resected gastric cancer patients: survey of a general
      hospital experience.
AB  - Between 1/1986 and 6/1996, 37 consecutive patients affected by node-positive
      gastric cancer (GC) were treated with radical surgery and received 5
      fluorouracil, epirubicin and mitomycin C (FEM) as adjuvant treatment. Only 57% of
      the patients received all six cycles and the reasons for treatment withdrawal
      were mainly related to concomitant pathologies and prolonged leukopenia. After a
      median follow-up of 39 months, the 3-year disease-free survival, disease-related
      survival and overall survival were 75.8%, 83.7% and 78.6% respectively. A
      statistically significant difference in survival was found in the subgroup of
      patients receiving more than three courses of treatment.

PMID- 9769390
TI  - Control of human vascular smooth muscle cell proliferation by sera derived from
      'experimentally stressed' individuals.
AB  - Recently we reported that individuals with high scores in standardized hostility
      evaluation tests, when placed in a environment, may have an association with
      increases in a blood-borne mitogenic substance(s) for arterial smooth muscle
      cells. To further investigate the molecular basis for such an association, PDS
      [plasma derived serum with platelet derived growth factor (PDGF) removed] from
      individuals showing the greatest differential pre/post-stress mitogenic activity,
      were tested for ability to modulate changes in the steady state of the c-myc mRNA
      in cultured VSMC (vascular smooth muscle cells) by Northern blot analysis. Post
      stress PDS resulted in a significant increase in c-myc mRNA, when compared with
      pre-stress PDS of the same individual. These results give further experimental
      support for the notion that stress (even in the form of transient, episodic
      psychological challenges) may affect the cardiovascular system via rapid elicited
      rises in serum mitogenic activity for VSMC.

PMID- 9769391
TI  - Treatments for newly diagnosed multiple myeloma: analysis of survival data and
      cost-effectiveness evaluation.
AB  - The main therapeutic options currently available to induce remission in newly
      diagnosed cases of multiple myeloma include: i) melphalan at conventional doses
      without concurrent administration of interferon; ii) melphalan at conventional
      dose combined with interferon; iii) autologous bone marrow transplantation
      (ABMT). We conducted an analysis of the survival data reported in five large
      scale published clinical trials and we evaluated the cost-effectiveness ratio. We
      determined the mean lifetime survival (MLS) for each treatment group using the
      Gompertz model. The cost data of patients given ABMT or standard chemotherapy
      were estimated from published information. The values of MLS were 3.47 years per
      patient for melphalan at conventional doses without interferon, 3.74 years for
      melphalan at conventional doses combined with interferon, and 7.28 years for
      ABMT. As compared with conventional melphalan treatment, ABMT yielded a
      significantly better survival. Survival after melphalan combined with interferon
      was not significantly different from that following melphalan alone. Using
      melphalan at conventional doses without interferon as reference term, the
      marginal cost-effectiveness ratio of ABMT was of about $26,000 per life year
      gained. For the induction treatment in patients with newly diagnosed myeloma,
      ABMT seems to be more effective and more cost-effective than the standard
      treatment with melphalan at conventional doses.

PMID- 9769392
TI  - Immunohistochemical study of MT-MMP tissue status in gastric carcinoma and
      correlation with survival analyzed by univariate and multivariate analysis.
AB  - Matrix metalloproteinase (MMP) expression is associated with advanced-stage
      cancer and contributes to tumor progression, invasion, and metastasis. Membrane
      type matrix metalloproteinase (MT-MMP) has a potential transmembrane domain at
      the C terminus and activates pro-MMP-2, which is mainly produced from
      interstitial fibroblasts. Its expression on the membrane of invasive tumor cells
      results in the pericellular space degradation at cell-matrix contact sites and
      renders cancer cells more invasive at the migration front. To elucidate the
      relationship between MT-MMP expression and metastasis and prognosis in gastric
      cancer patients, MT-MMP expression was analyzed immunohistochemically in 127
      primary tumors and results were correlated with several prognostic parameters and
      patient's survival. MT-MMP immunoreactivity was stained on the cell membrane of
      cancer cells and fibroblasts in the invasion front. MT-MMP was detected in 72
      tumors (57%) (MT-MMP-positive). MT-MMP expression was closely associated with
      macroscopically invasive type, nodal involvement, lymphatic invasion, vessel
      invasion, and peritoneal dissemination. Patients with MT-MMP-positive tumor had a
      significantly worse prognosis than those with MT-MMP-negative tumor (p<0.001).
      Multivariate analysis showed MT-MMP overexpression as an independent prognostic
      factor in gastric cancer patients. Immunohistochemical analysis for MT-MMP may be
      an indicator of metastatic potential or the prognosis of gastric cancer patients.

PMID- 9769393
TI  - Evidence of multi-step oncogenesis of oral squamous cell carcinoma.
AB  - We examined biopsy samples from one oral cancer and three precancerous lesions of
      the tongue of an 81-year old woman by polymerase chain reaction single-strand
      conformation polymorphism (PCR-SSCP) and sequence analyses using 18
      oligonucleotide primer pairs of adenomatous polyposis coli (APC) gene and 5
      primers of p53 gene. Normal tongue epithelium adjacent to lesions was used as a
      control. The four lesions harbored the common mutation of APC gene that was not
      detected in the control. At codon 1621 in exon 15 of the APC gene there was a C
      to G substitution resulting in serine (TCA) to stop codon (TGA). No mutation of
      p53 gene was detected in any samples of the control and three precancerous
      lesions of the tongue. On the other hand, an A to G substitution at codon 170 in
      exon 5 of p53 gene resulting in glutamic acid (ACG) to glycine (GCG) was detected
      in the DNA of her tongue cancer. These results may suggest that the four lesions
      have the same origin, and that multi-step oncogenesis had occurred, the APC gene
      alteration being one of the early events in the process of tumorigenesis and p53
      gene alteration involved in the late events.

PMID- 9769394
TI  - In vitro carboplatin-mesna interaction in aqueous solution, human plasma and
      urine.
AB  - The chemotherapeutic benefit of synergistic drug combinations and higher drug
      dosages has generated interest in the application of these regimens to cancer
      patients. A major obstacle in the application of these strategies to the
      treatment of cancer is the dose-limiting toxicities of drug combinations. Sodium
      2-mercaptoethane-sulfonate (mesna), a chemoprotective drug, may reduce the
      nephrotoxicity of carboplatin [CBDCA, paraplatin, JM-8, cis-diammine (1,1
      cyclobutane dicarboxylato) platinum II] when administered in combination
      chemotherapy. The purpose of this study was to evaluate, compare and contrast in
      vitro the interaction of mesna with carboplatin in aqueous solution, human plasma
      and urine. Carboplatin and mesna were incubated separately and together at
      clinically relevant concentrations in plasma and urine. The concentration of
      carboplatin was assayed by HPLC, and the decay of carboplatin alone and in
      combination with mesna was compared. The incubation of carboplatin with mesna in
      human plasma up to 8 days did not result in a statistically significant
      interaction: the half-life of carboplatin in plasma when it was combined with
      mesna was 1.62 +/- 0.08 (SE) days compared to 1.85+/- 0.04 (SE) days for
      carboplatin by itself. The incubation of drugs in fresh human urine up to 15 days
      gave a half-life of 3.43+/- 0.8 (SE) days for carboplatin alone and 2.78 +/- 0.7
      (SE) days for carboplatin when it was combined with mesna. Our results show that
      carboplatin and mesna do not significantly interact in plasma. Although a
      statistically significant difference between the half-life of carboplatin and the
      half-life of the carboplatin/mesna combination is detected in urine, it is not
      likely to be clinically significant, as there is no significant interaction
      detected in the first 48 h). It is thus unlikely that mesna would substantially
      affect the pharmacokinetics of carboplatin when both are given together to
      patients as part of combination chemotherapy regimens.

PMID- 9769395
TI  - Clinical evaluation of two dosages and schedules of ifosfamide in combination
      with cisplatin in neo-adjuvant chemotherapy of patients with advanced (stage III
      IV) head and neck squamous cell carcinoma: a phase II randomized study.
AB  - The aims of the present open, randomized, single-blind (patient), single
      institution, phase II study were: i) to compare the therapeutic effectiveness and
      toxicity of two dosages and schedules of ifosfamide (IFO) in combination with
      cisplatin (CDDP) mainly in the neo-adjuvant setting of patients (pts) with
      locally advanced (stage III-IV) head and neck squamous cell cancer (HNSCC)
      (primary endpoint); ii) to assess the quality of life (QL) of pts included in the
      study before and after treatment (secondary endpoint). From July 1996 to June
      1997, 28 pts, all males (mean age 56.79 years, range 37-72), hospitalized in the
      Department of Medical Oncology, University of Cagliari, were enrolled in the
      study. Twenty pts (M/F 20/0, mean age 53.6, range 37-71 years; stage III 1 pt,
      stage IV 19 pts) were evaluable for response and all 28 pts enrolled were
      evaluable for toxicity. Arm A: IFO 2.2 g/m2 i.v. as a 4 h infusion on days 1-5,
      Mesna 600 mg i.v. as push injection at 0 h, 4 h, 8 h on days 1-5, CDDP 20 mg i.v.
      as a 60 min infusion on days 1-5. The regimen was repeated every 28 days for 2
      cycles. Fifteen pts (11 of whom were evaluable) were enrolled in this Arm. Arm B:
      IFO 1.5 g/m2 i.v. as a 4 h infusion on days 1-5, Mesna 600 mg i.v. as push
      injection at 0 h, 4 h, 8 h on days 1-5, CDDP 20 mg i.v. as a 60 min infusion on
      days 1-5. The regimen was repeated every 28 days for 3 cycles. Thirteen pts (9 of
      whom were evaluable) were enrolled in this Arm. The two Arms were well-balanced
      for sex, age, site of primary, ECOG PS and clinical stage. After completion of 2
      (Arm A) or 3 (Arm B) cycles of chemotherapy, the pts were assessed for response.
      All evaluable pts received treatment as planned. Six pts (54.5%) of Arm A and 4
      pts (44.5%) of Arm B had partial response (PR) with an overall response rate
      (ORR) of 54.5% and 44.5%, respectively: it is worth noting that all (100%) pts
      who had PR in Arm B achieved a high-grade PR, i.e. >/=70%, whereas only one pt
      (16.7%) who had PR in Arm A achieved a high-grade PR. Three pts (27.3%) in Arm A
      and 2 pts (22.2%) in Arm B had stable disease (SD); 2 pts (18.2%) in Arm A and 3
      pts (33.3%) in Arm B had progressive disease (PD). The actual dose intensity was
      over 80% of the projected dose intensity for both drugs and for both Arms. Over a
      total of 59 cycles administered, the total number of episodes of toxicity was 24
      for Arm A and 17 for Arm B. Three pts out of 28 evaluable for toxicity (10.8%)
      died for Grade 5 hematological toxicity: all pts were included in Arm A. In Arm
      A, 2 pts (13.3%) experienced hematological Grade 3 toxicity and 2 pts (13.3%)
      hematological Grade 4 toxicity. In Arm B no pt experienced Grade 3-4
      hematological toxicity. No Grade 3-4 toxicity of any other type was found in
      either Arm. The QL evaluation, using the Cella's FACT-G scale supplemented with
      disease-specific scale (FACT-H&N scale), did not show significant beneficial
      effect of neo-adjuvant chemotherapy treatment.

PMID- 9769396
TI  - Expression of transmembrane 4 superfamily member, CD9, is related to improved
      progression-free survival in patients with diffuse non-Hodgkin's lymphoma.
AB  - Decreased expression of the transmembrane 4 superfamily member, CD9, is
      associated with poor prognosis in patients with breast or non-small cell lung
      cancer. The expression of CD9 in lymphoma was examined in this study. Fifty-one
      sections with diffuse lymphomas were examined. Thirty-seven had low expression
      and 14 high expression of CD9. At 5 years the progression-free survival rates
      were 83.3+/-10.8% and 32.8+/-9.2% (p=0.018), and the actual survival were 83.3+/
      10.8% and 56.8+/-8.9% (p=0.256) for those with high and low CD9 expression
      respectively. Decreased expression of CD9 appears to be a prognostic factor for
      poor survival in patients with diffuse lymphomas.

PMID- 9769398
TI  - Tumor-reactive immunoglobulins in ovarian cancer: diagnostic and therapeutic
      significance? (review).
AB  - Inhibition of the immune system has been observed in association with most stages
      of ovarian cancer; however, the mechanisms involved in the induction and
      maintenance of this chronic immune unresponsiveness associated with cancer
      progression are poorly understood. This immunosuppressed state is primarily
      defined as the failure to eradicate the tumor. This immunosuppressed state is
      generally associated with decreased numbers and reactivity of lymphoid cells in
      women with ovarian cancer. The degree of immune dysfunction in ovarian cancer
      patients has been demonstrated to correlate with patient survival. While ovarian
      cancer patients generally fail to exhibit effective immunosurveillance, as
      manifested by continued tumor growth and progression, the presence of tumor
      reactive immunoglobulins can be demonstrated in these women, indicating the
      continued presence of immune recognition. We have not only demonstrated the
      presence of tumor-reactive antibodies in ovarian cancer patients, but have also
      shown that the levels of these antibodies increase as the disease progresses. The
      antigens recognized by the patients' humoral response have been identified as
      either membrane-associated or intra-cellular. In general, the localization of
      these antigens tend to be linked to the patient's prognosis. The presence of a
      humoral response against intracellular proteins are correlated with poor
      prognosis, while autoantibodies reactive with surface components appear to have a
      better prognosis. In addition to general antigen recognition, these reactive
      antibodies have been utilized to define specific epitopes on tumor-associated
      proteins. Certain specific antigenic epitopes exhibit common recognition among
      patients with the same tumor type. The specific recognition of certain epitopes
      can provide early evidence of aberrant protein expression and this aberrant
      expression of certain proteins, such as procathepsin D, appear to be linked to
      the tumor's acquisition of specific malignant characteristics, including
      metastasis formation and chemoresistance. Despite the existence of circulating
      tumor-reactive immunoglobulins, their presence correlates, in general, with poor
      prognosis and poor host survival. Since tumor-reactive immunoglobulins are
      elicited and can be detected early in the development of tumors and their
      enhanced synthesis is induced prior to the clinical manifestation of recurrence,
      the assessment of the tumor-reactive immune response against specific antigenic
      epitopes should represent an early significant diagnostic and prognostic marker
      in ovarian cancer.

PMID- 9769397
TI  - Treatment of subdiaphragmatic Hodgkin's disease: long-term results and side
      effects.
AB  - To evaluate the results, prognostic factors and especially side-effects of the
      treatment for subdiaphragmatic Hodgkin's disease (SHD) a retrospective study was
      conducted in the Haematology Departments and in the Cancer Centres of Nancy and
      Strasbourg between 1976 and 1990; 55 patients corresponding to the IA to IIB SHD
      stages were analysed. The median age was 45 years. In accordance with Ann Arbor
      classification, we observed 12 CS IA (21.3%), 2 CS IB (3.5%), 14 CS IIA (25.4%)
      and 27 CS IIB (49.7%). Twenty-five patients (45.4%) underwent laparotomy with
      spleen involvement in 10 cases. Fifteen patients (27.3%) had exclusive
      radiotherapy, 10 by inverted-Y field with or without splenic field, 5 by limited
      field to inguinal and homolateral iliac nodes. Forty patients had prior
      chemotherapy, 18 by MOPP protocol, 18 by hybrid MOPP/ABVD protocol and 4 by other
      schemes. The total dose delivered ranged from 26 to 45 Gy. With a median follow
      up of 8 years, the overall and disease specific survival rates are respectively
      61% and 83% at 10 years. Nine patients relapsed (16.4%), 4 among the 15 (26.6%)
      treated by exclusive irradiation and 5 among the 40 (12.5%) treated by combined
      therapy. We observed 8.3%, 21.4% and 18.5% of relapses respectively among the
      clinical stages IA, IIA and IIB. Eleven patients (20%) developed a second cancer.
      Twenty-six long-term complications were noted, nine of which concerned the
      digestive system. The only significant prognostic factor is age, with 10-year
      specific survival rates of 96% and 66% respectively for patients younger and
      older than 50 years (p=0.0003). Our data confirm that the most appropriate
      treatment for stage IA is exclusive radiotherapy and combined therapy for all
      other cases. With the use of CT-scan and eventually lymphography, the laparotomy
      is reserved only for cases with an uncertain diagnosis. Tobacco use is also
      clearly a risk factor in our series for late vascular complications and second
      cancers.

PMID- 9769399
TI  - Cancer of the anus (review).
AB  - Cancers of the anus differ in their histology, anatomical location, response to
      therapy and prognosis. Epidermoid cancers have turned out to be one of the tumors
      most responsive to multimodality treatment, for which radical surgery is no
      longer the primary modality of choice.

PMID- 9769400
TI  - Lobular carcinoma in situ of the breast: results of a radiosurgical conservative
      treatment.
AB  - From 1980 to 1992, 17 women underwent lumpectomy (13) or quadrantectomy (4) and
      whole breast irradiation (median dose: 52 Gy) for pure lobular carcinoma in situ
      (LCIS). Three cases correspond to palpable lesions and 14 were discovered only by
      mammography. Twelve women also received tamoxifen at 20 mg/day for two years.
      With a median follow-up of 88 months, no local or regional recurrences have been
      recorded. The global rate of bilateral carcinoma was 17.6% (2 synchronous and one
      metachronous). In the literature, only eight other cases of LCIS were treated by
      lumpectomy and radiation therapy, but without details and data on long-term
      results. After biopsy alone for LCIS subsequent infiltrating carcinoma occurred
      in about 15% of the cases. Thus, the classical radiosurgical association should
      represent an interesting alternative both for biopsy alone and radical surgery
      until now only proposed to treat LCIS.

PMID- 9769401
TI  - Manipulation of the immune response of mice against neu/HER2-expressing tumours.
AB  - The rat oncogene neu, and its human homologue HER2, can both cause cell
      transformation in vitro and tumour formation in vivo, albeit by different
      mechanisms. 3T3 cells (B104.1.1) transfected with mutated neu (neu) grow as solid
      tumours in Swiss mice. The purpose of this study was to determine whether
      immunization with extracts of different 3T3 lines expressing these oncoproteins
      would lead to a cross-reactive response, and whether this response could alter
      B104. 1.1 tumour growth. Both humoral and cellular cross-reactive responses were
      observed, which were capable of inhibiting tumour growth in vivo. This cross
      reactive response may be relevant to the immunotherapy of HER2-expressing tumours
      in humans.

PMID- 9769402
TI  - Effect of dietary soy protein isolate, genistein, and 1,4
      phenylenebis(methylene)selenocyanate on DNA binding of 7,12
      dimethylbenz[a]anthracene in mammary glands of CD rats.
AB  - We examined whether a soy protein isolate or one of its major components
      (genistein) influences the initiation stage of carcinogenesis via DNA binding
      studies of 7,12-dimethylbenz[a]anthracene (DMBA) in liver and mammary tissue of
      female CD rats. A semipurified high-fat diet (23.5% corn oil) containing the soy
      protein isolate (10%), genistein (111 ppm), or 1,4
      phenylenebis(methylene)selenocyanate (p-XSC) (5 ppm as selenium) as a positive
      control was fed to 6-week-old virgin female CD rats for 1 week before carcinogen
      treatment. Neither soy nor genistein affected the extent of DMBA-DNA binding in
      liver. In mammary tissue, 111 ppm genistein in the diet was more effective than
      the soy protein isolate, although the latter contains the same amount of
      genistein, mainly present as a glucoside conjugate. As shown before, p-XSC
      inhibited DMBA-DNA binding in mammary tissue. Total binding was inhibited because
      of reduced formation of three major adducts: anti-diol epoxide deoxyguanosine,
      syn-diol epoxide deoxyadenosine, and anti-diolepoxide deoxyadenosine. Thus, an
      additional experiment with 111 and 222 ppm of genistein was performed; 222 ppm
      genistein had a weaker effect than that observed for 111 ppm. Nevertheless, 111
      ppm of genistein in the diet appears to inhibit the initiation phase of DMBA
      induced rat mammary tumors and may partially account for the reported inhibitory
      effect of soy against DMBA-induced rat mammary tumors.

PMID- 9769403
TI  - Analysis of long-term survival in patients with locally advanced non-small cell
      lung cancer.
AB  - Neoadjuvant combined radiochemotherapy followed by definitive tumor resection
      improved survival in patients with locally advanced non-small cell lung cancer
      (NSCLC). Fifty-four patients (NSCLC IIIa + IIIb) were treated with combined
      radiochemotherapy within a phase I/II study. Twenty-six patients had been
      resected after combined neoadjuvant treatment and this group was evaluated
      concerning long-term survival. The median survival for patients with stage IIIa
      tumor was calculated to be 26 months and 13 months for patients with IIIb status.
      Patients with no viable tumor cells in the mediastinal lymph nodes had a
      significantly better survival probability than patients with residual microscopic
      lymph node disease (p=0.038). Patients with no viable tumor cells had a 1-year (2
      year) survival rate of 100% (60%) versus 58% (42%) for patients with residual
      microscopic tumor in the mediastinal nodes. No significant difference between the
      N1- and the N2-status was seen. Hence, response to neo-adjuvant radiochemotherapy
      seems to be an additional important prognostic factor in patients with advanced
      NSCLC.

PMID- 9769404
TI  - Unique presentation of a granular cell tumor as a paratracheal mass.
AB  - An unusual presentation of a granular cell tumor is reported with a review of the
      natural history and pathologic characteristics of this tumor. Our patient was
      asymptomatic and presented with a mass in the inferior right neck on routine
      physical examination. Preoperative radiologic evaluation suggested a parathyroid
      adenoma but the normal parathormone level was inconsistent with this diagnosis.
      At surgery, a firm mass was identified inferior to the right lobe of the thyroid
      gland and was found to represent a granular cell tumor densely adherent to the
      trachea. This case demonstrates a unique presentation for this relatively rare
      neoplasm which was treated with complete surgical resection.

PMID- 9769405
TI  - Treatment of renal cancer patients with gemcitabine (2',2'-difluorodeoxycytidine)
      and interferons: antitumor activity and toxicity.
AB  - Combined therapy of gemcitabine with interferons on patients with histologically
      confirmed metastatic renal cell carcinoma is reported. Patients had an
      unfavourable disease due to documented tumor progression after various interferon
      alpha-based immunotherapy (26 weeks on average). The median number of metastatic
      sites was 6.1 per patient and 78% of the patients exhibited >/= 4 lesions. Nine
      evaluable patients received at least 6 doses of gemcitabine and 8 doses of
      interferon-gamma. Overall, therapy resulted in a remission rate of 15% (4 x
      partial response; 4 x minor response) for single measurable lesions (n=53).
      Remissions were more often found for lesions, that did not progress at baseline
      evaluation (n=30; OR: 20%), compared to 8.7% for sites in progression (n=23).
      However, as a result of therapy, 43.5% of the progressive lesions did not
      continue to progress. Although only one of nine patients finally overall achieved
      a minor remission and one patient a stable disease, the median time to tumor
      progression (6.1 months) and the median survival (13.5 months) was favourable. In
      conclusion, the combination of gemcitabine and interferon demonstrated cytotoxic
      and cytostatic effects on metastases of renal cell carcinoma at a tolerable
      toxicity, thus controlled clinical studies for first line therapy with
      gemcitabine and interferon are in progress.

PMID- 9769406
TI  - Comparison of Cyfra 21-1, TPA and SCC tumor markers in esophageal squamous cell
      carcinoma.
AB  - The tumor markers Cyfra 21-1, TPA and SCC were assayed in a series of 96 patients
      with squamous cell carcinoma of the esophagus. Sensitivity was 42% for Cyfra 21
      1, 40% for TPA and 37% for SCC. Combining Cyfra 21-1 and SCC gave a 56%
      sensitivity and combining TPA and SCC a 58% sensitivity. Sensitivity varied with
      disease stage and was particularly good in stage IV disease. Tumor markers did
      not vary with tumor differentiation. SCC levels were higher in tumors in the
      upper third of the esophagus. Pre-treatment levels of Cyfra 21-1 correlated with
      histological response. Cyfra 21-1 was also the only marker which distinguished
      significantly different survival curves. In multivariate analysis, however,
      treatment was the only independent factor predictive of survival.

PMID- 9769407
TI  - E-cadherin and associated molecules in the invasion and progression of prostate
      cancer.
AB  - Prostatic carcinoma is the most common type of male cancer found in the Western
      world and its distant metastasis becomes a life threatening event in tumour
      bearing patients. However, the biology of prostate cancer and metastasis is
      poorly understood. We review the progress made in the last decade on the
      molecular and cellular biology of cell-cell adhesion molecules in the invasion
      and progression of prostate cancer, with emphasis being placed on E-cadherin and
      its associated molecules.

PMID- 9769408
TI  - The immune response of rat spleen to dietary fibers and to low doses of
      carcinogen: morphometric and immunohistochemical studies.
AB  - The effects of high-fiber diets on anticancer immune response are often masked by
      the effects of high-dose carcinogens. Using low levels of carcinogen the splenic
      immune response can be evaluated. Colon tumors were induced in rats with low
      doses of 1, 2-dimethylhydrazine, in the following experimental groups: rats fed
      with low fiber diet without exposure to carcinogen; rats exposed to the
      carcinogen and fed with low-fiber diet; rats exposed to carcinogen, and
      maintained on high-fiber diets, and did not develop tumors; and rats that
      developed tumors after exposure to carcinogen and maintenance on either low-fiber
      or high-fiber diets. After 24 weeks their spleens were studied
      immunohistochemically and morphometrically. In tumor-free rats, low doses of
      carcinogen caused significant response of the lymphoid system. This was
      manifested in the intensive blast transformation and in an increase in the number
      of dendritic cells and macrophages in different structures of the spleen. Dietary
      fibers activated these processes: the number of Ki-67 positive cells, macrophages
      and plasma cells increased significantly in the red pulp. A positive correlation
      was found between the effects of the carcinogen and proliferation of lymphocytes
      in the white pulp, and to lesser degree between high-fiber diets and lymphocytic
      abundance in the red pulp. The number of splenic apoptotic lymphocytes decreased
      in rats exposed to carcinogen. In tumor-bearing rats, immune insufficiency of the
      splenic responses was seen in the significant decrease of the areas of the mantle
      layer and the periarterial sheaths, as result of the decreased number of
      lymphocytes. Dietary fibers reduced the degree of this insufficiency. Even low
      doses of carcinogen cause a significant splenic immune response. This reaction
      has a compensatory character with macrophages, B and T cells participating.
      Addition of any high-fiber diet after the exposure to carcinogen activated the
      lymphocyte proliferation in the spleen.

PMID- 9769409
TI  - Enhancement of spontaneous transmitter release at neonatal mouse neuromuscular
      junctions by the glial cell line-derived neurotrophic factor (GDNF).
AB  - 1. The acute effects of neurotrophic factors on the frequency of spontaneous
      transmitter release (miniature endplate potentials (MEPPs)) from motor nerve
      terminals has been examined in skeletal muscles of neonatal mice aged between 9
      and 20 days. The following factors were tested at a concentration of 50 ng ml-1:
      brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4
      (NT-4), ciliary neuronotrophic factor (CNTF), leukaemia inhibitory factor (LIF),
      insulin-like growth factors 1 and 2 (IGF-1 and IGF-2), and glial cell line
      derived neurotrophic factor (GDNF). In some experiments, the responses to 2
      microM LaCl3 and 10 mM K+, or to 2-5 nM purified alpha-latrotoxin (alpha-LTX)
      were also measured. 2. Neither BDNF, NT-3, NT-4, LIF, IGF-1 or IGF-2 - singly or
      in combination - caused any significant change in MEPP frequency. GDNF, however,
      produced a highly significant, 2-fold increase in neurotransmitter release that
      was reproduced in fourteen muscles. 3. Potentiation of MEPP frequency in GDNF was
      of the same order as that induced by tetanic stimulation or substitution of the
      bathing medium with hypertonic saline; but substantially less than that induced
      either by lanthanum ions or alpha-latrotoxin. 4. The data suggest that
      concentrations of GDNF that produce maximal enhancement of motoneurone survival
      in vitro and in vivo also produce acute, non-saturating enhancement in
      transmitter release at immature mammalian neuromuscular synapses. Taken together
      with other reports, these findings suggest that GDNF may mediate both functional
      and structural plasticity of neonatal neuromuscular junctions.

PMID- 9769410
TI  - Laminar difference in GABA uptake and GAT-1 expression in rat CA1.
AB  - 1. The axonal plexus of most hippocampal interneurons is restricted to certain
      strata within the target region. This lamination suggests a possible functional
      heterogeneity of inhibitory synapses between different interneurons and CA1
      pyramidal cells. 2. We therefore compared inhibitory postsynaptic potentials
      (IPSPs) and currents (IPSCs) in CA1 pyramidal cells, which were evoked from two
      stimulation sites (stratum oriens and stratum radiatum). Stimulation in stratum
      oriens yielded faster decaying IPSPs and IPSCs than stimulation in stratum
      radiatum. 3. IPSP and IPSC kinetics were regulated by GABA uptake in both layers
      as indicated by the prolongation of the signals under tiagabine, a GAT-1
      (neuronal GABA plasma membrane transporter)-specific GABA-uptake blocker.
      However, the effect of tiagabine was significantly more pronounced following
      stimulation in stratum radiatum than in stratum oriens (prolongation of IPSC half
      decay time by 167 vs. 115 %, respectively). 4. In situ hybridization with
      antisense mRNA for the GABA-synthesizing enzyme glutamate decarboxylase
      (GAD65/67) and the GABA transporter GAT-1 showed that the proportion of
      interneurons expressing GAT-1 was lower in stratum oriens than in stratum
      radiatum/lacunosum-moleculare. 5. From these functional and molecular data we
      conclude that the regulation of IPSP and IPSC kinetics in CA1 pyramidal cells by
      neuronal GABA uptake differs between layers. Our findings suggest that this
      laminar difference is caused by a lower expression of GAT-1 in interneurons in
      stratum oriens than in stratum radiatum/lacunosum-moleculare.

PMID- 9769411
TI  - Na+-Ca2+ exchange and sarcoplasmic reticular Ca2+ regulation in ventricular
      myocytes from transgenic mice overexpressing the Na+-Ca2+ exchanger.
AB  - 1. The contribution of the sarcoplasmic reticulum (SR) and Na+-Ca2+ exchanger to
      intracellular Ca2+ regulation in mouse cardiac myocytes was investigated by
      measuring contraction after variable rest intervals, rapid cooling contractures
      (RCCs) and fast application of caffeine. The results obtained showed differences
      from other species in the roles played by the SR and the Na+-Ca2+ exchanger. They
      suggest that in mouse ventricular myocytes there is significant Ca2+ entry via
      the exchanger during rest and during the latter part of the Ca2+ transient. 2. In
      cardiac myocytes isolated from transgenic mice overexpressing the cardiac Na+
      Ca2+ exchanger the time to peak and relaxation of twitches and RCCs were faster
      than in control littermates. The decline of Ca2+, assessed by indo-1
      fluorescence, was faster in transgenic myocytes even in the absence of Na+ and
      Ca2+ in the superfusing solution. This suggests that SR Ca2+ uptake is faster in
      these myocytes. However, no difference in the expression of SERCA2a,
      phospholamban or calsequestrin measured with Western blotting could be found in
      the two groups. 3. We measured SR Ca2+ content by integrating the caffeine
      induced transient inward current. The amount of Ca2+ stored in the SR of
      transgenic mouse myocytes was 69 % greater than in non-transgenic littermates.
      The increased SR Ca2+ content may be responsible for the faster rate of SR Ca2+
      release and uptake in cells from transgenic mice. 4. We performed experiments to
      assess whether the reversal potential of the Na+-Ca2+ exchanger (ENa-Ca) was
      different in transgenic cardiac cells. We measured a Ni2+-sensitive current
      elicited by voltage ramps in non-dialysed myocytes. The current-voltage
      relationship showed no difference in the reversal potential of the Na+-Ca2+
      exchanger in transgenic and control myocytes. This suggests that the effects on
      the SR Ca2+ content in transgenic cardiac myocytes can be ascribed to the
      overexpression of the exchanger and are not secondary to changes in intracellular
      diastolic Ca2+ and Na+.

PMID- 9769412
TI  - Intercellular Ca2+ waves in rat heart muscle.
AB  - 1. Confocal laser scanning microscopy was used to visualize intercellular
      transmission of Ca2+ waves in intact rat ventricular trabeculae micro-injected
      with the calcium indicator fluo-3. 2. Ca2+ waves usually failed to be transmitted
      from cell to cell. At identified individual end-to-end cell contacts, successful
      transmission interspersed with failure, which sometimes occurred despite an
      apparent small spritz of Ca2+ between cells. The probability of cell to cell
      transmission (Ptran) was 0.13. 3. Ca2+ waves arose preferentially near junctions
      of connected cells, where connexin-43 was found, but randomly in enzymatically
      disconnected heart cells. 4. beta-Adrenergic stimulation significantly increased
      Ptran (to 0.22) and heptanol, an uncoupler of gap junction channels,
      significantly decreased it (to 0.045). 5. In regions of high [Ca2+]i due to
      damage, wave frequency decreased markedly with each cell-cell junction passed. 6.
      The Ca2+ permeability of cardiac gap junctions may be regulated, and the low
      ability of cardiac gap junctions to transmit Ca2+ may help control the spread of
      Ca2+ from damaged regions.

PMID- 9769413
TI  - Direct measurement of SR release flux by tracking 'Ca2+ spikes' in rat cardiac
      myocytes.
AB  - 1. Ca2+ release flux across the sarcoplasmic reticulum (SR) during cardiac
      excitation-contraction coupling was investigated using a novel fluorescence
      method. Under whole-cell voltage-clamp conditions, rat ventricular myocytes were
      dialysed with a high concentration of EGTA (4.0 mM, 150 nM free Ca2+), to
      minimize the residence time of released Ca2+ in the cytoplasm, and a low
      affinity, fast Ca2+ indicator, Oregon Green 488 BAPTA-5N (OG-5N; 1.0 mM, Kd
      approximately 31 microM), to optimize the detection of localized high [Ca2+] in
      release site microdomains. Confocal microscopy was employed to resolve
      intracellular [Ca2+] at high spatial and temporal resolution. 2. Analytical and
      numerical analyses indicated that, under conditions of high EGTA concentration,
      the free [Ca2+] change is the sum of two terms: one major term proportional to
      the SR release flux/Ca2+ influx, and the other reflecting the running integral of
      the released Ca2+. 3. Indeed, the OG-5N transients in EGTA-containing cells
      consisted of a prominent spike followed by a small pedestal. The OG-5N spike
      closely resembled the first derivative (d[Ca2+]/dt) of the conventional Ca2+
      transient (with no EGTA), and mimicked the model-derived SR Ca2+ release function
      reported previously. In SR Ca2+-depleted cells, the OG-5N transient also closely
      followed the waveform of L-type Ca2+ current (ICa). Using ICa as a known source
      of Ca2+ influx, SR flux can be calibrated in vivo by a linear extrapolation of
      the ICa-elicited OG-5N signal. 4. The OG-5N image signal was localized to
      discrete release sites at the Z-line level of sarcomeres, indicating that the
      local OG-5N spike arises from 'Ca2+ spikes' at transverse (T) tubule-SR junctions
      (due to the imbalance between calcium ions entering the cytosol and the buffer
      molecules). 5. Both peak SR release flux and total amount of released Ca2+
      exhibited a bell-shaped voltage dependence. The temporal pattern of SR release
      also varied with membrane voltage: Ca2+ release was most synchronized and
      produced maximal peak release flux (4.2 mM s-1) at 0 mV; in contrast, maximal
      total release occurred at -20 mV (71 versus 61 microM at 0 mV), but the localized
      release signals were partially asynchronous. Since the maximal conventional
      [Ca2+] transient and contraction were elicited at 0 mV, it appears that not only
      the amount of Ca2+ released, but also the synchronization among release sites
      affects the whole-cell Ca2+ transient and the Ca2+-myofilament interaction.

PMID- 9769414
TI  - Mechanistic link between lidocaine block and inactivation probed by outer pore
      mutations in the rat micro1 skeletal muscle sodium channel.
AB  - 1. Mutations that disrupt Na+ channel fast inactivation attenuate lidocaine
      (lignocaine)-induced use dependence; however, the pharmacological role of slower
      inactivation processes remains unclear. In Xenopus oocytes, tryptophan
      substitution in the outer pore of the rat skeletal muscle channel (micro1-W402)
      alters partitioning among fast- and slow-inactivated states. We therefore
      examined the effects of W402 mutations on lidocaine block. 2. Recovery from
      inactivation exhibited three kinetic components (IF, fast; IM, intermediate; IS,
      slow). The effects of W402A and W402S on IF and IS differed, but both mutants
      (with or without beta1 subunit coexpression) decreased the amplitude of IM. In
      wild-type channels, lidocaine imposed a delayed recovery component with
      intermediate kinetics, and use-dependent block was attenuated in both W402A and
      W402S. 3. To examine the pharmacological role of IS relative to IM, drug-exposed
      beta1-coexpressed channels were subjected to 2 min depolarizations. Lidocaine had
      no effect on sodium current (INa) after a 1 s hyperpolarization interval that
      allowed recovery from IM but not IS, suggesting that lidocaine affinity for IS is
      low. 4. Both W402 mutations reduced occupancy of IM in drug-free conditions, and
      also induced resistance to use-dependent block. We propose that lidocaine-induced
      use dependence may involve an allosteric conformational change in the outer pore.

PMID- 9769415
TI  - The influence of caffeine on intramembrane charge movements in intact frog
      striated muscle.
AB  - 1. The influence of caffeine, applied over a 25-fold range of concentrations, on
      intramembrane charge movements was examined in intact voltage-clamped amphibian
      muscle fibres studied in the hypertonic gluconate-containing solutions that were
      hitherto reported to emphasize the features of qgamma at the expense of those of
      qbeta charge. 2. The total charge, Qmax, the transition voltage, V*, and the
      steepness factor, k, of the steady-state charge-voltage relationships, Q(V), were
      all conserved to values expected with significant contributions from the steeply
      voltage-dependent qgamma species (Qmax approximately 20 nC microF-1, V*
      approximately -50 mV, k approximately 8 mV) through all the applications of
      caffeine concentrations between 0.2 and 5.0 mM. This differs from recent reports
      from studies in cut as opposed to intact fibres. 3. The delayed transients that
      have been attributed to transitions within the qgamma charge persisted at low
      (0.2 mM) and intermediate (1.0 mM) caffeine concentrations. 4. In contrast, the
      time courses of such qgamma currents became more rapid and their waveforms
      consequently merged with the earlier qbeta decays at higher (5.0 mM) reagent
      concentrations. The charging records became single monotonic decays from which
      individual contributions could not be distinguished. This suggests that caffeine
      modified the kinetic properties of the qgamma system but preserved its steady
      state properties. These findings thus differ from earlier reports that high
      caffeine concentrations enhanced the prominence of delayed transient components
      in cut fibres. 5. Caffeine (5.0 mM) and ryanodine (0.1 mM) exerted antagonistic
      actions upon qgamma charge movements. The addition of caffeine restored the
      delayed time courses that were lost in ryanodine-containing solutions, reversed
      the shift these produced in the steady-state charge-voltage relationship but
      preserved both the maximum charge, Qmax, and the steepness, k, of the steady
      state Q(V) relationships. 6. Caffeine also antagonized the actions of tetracaine
      on the total available qgamma charge, but did so only at the low and not at the
      high applied concentrations. Thus, 0.2 mM caffeine restored the steady-state
      qgamma charge, the steepness of the overall Q(V) function and the appearance of
      delayed qgamma charge movements that had been previously abolished by the
      addition of 2.0 mM tetracaine. 7. In contrast, the higher applied (1.0 and 5.0
      mM) caffeine concentrations paradoxically did not modify these actions of
      tetracaine. The total charge and voltage dependence of the Q(V) curves, and the
      amplitude and time course of charge movements remained at the reduced values
      expected for the tetracaine-resistant qbeta charge. 8. These results permit a
      scheme in which caffeine acts directly upon ryanodine receptor (RyR)-Ca2+ release
      channels whose consequent activation then dissociates them from the tubular
      dihydropyridine receptor (DHPR) voltage sensors that produce qgamma charge
      movement, with which they normally are coupled in reciprocal allosteric contact.

PMID- 9769417
TI  - Facilitatory effect of Ca2+ on the noradrenaline-evoked cation current in rabbit
      portal vein smooth muscle cells.
AB  - 1. The facilitatory effect of external calcium ions (Ca2+o) on the alpha1
      adrenoceptor-activated non-selective cation current (Icat) was investigated in
      rabbit portal vein cells using noise and voltage-jump relaxation analysis of the
      whole-cell macroscopic current. 2. Micromolar concentrations of Ca2+o potentiated
      the peak amplitude of Icat at a holding potential (Vh) of -50 mV. The effective
      [Ca2+]o which produced a 50% potentiation (EC50) was 3 microM. 3. From noise
      analysis the estimated single channel conductance (gamma) was approximately 23 pS
      with [Ca2+]o between 3 and 100 microM, whereas in < 10 nM or 1 microM Ca2+o gamma
      was approximately 10 pS. 4. The spectral density function of Icat at negative
      potentials could be described by the sum of two Lorentzians in every [Ca2+]o
      examined. The time constant of the lower frequency Lorentzian component (tau1)
      was about 11 ms in < 10 nM Ca2+o and was about 45 ms in micromolar concentrations
      of Ca2+o (1-100 microM). In contrast, the time constant of the higher frequency
      component (tau2) was similar in < 10 nM Ca2+o and 100 microM Ca2+o (between 1 and
      2 ms). 5. The lower frequency Lorentzian component was responsible for about half
      the total current variance in < 10 nM Ca2+o whereas in micromolar concentrations
      of Ca2+o it was responsible for most of the measured current variance. 6. In
      voltage-jump experiments, on stepping the voltage from -50 to +50 mV the
      instantaneous current was followed by an exponential decline of Icat. Stepping
      back to -30 mV produced an exponential inward relaxation (Irelax,-30 mV) leading
      to an increase in the steady-state amplitude of Icat in micromolar concentrations
      of Ca2+o, but this relaxation was not observed in < 10 nM Ca2+o. The relative
      amplitude of Irelax,-30 mV increased in an [Ca2+]o-dependent manner (EC50 was 2
      microM) although the time constant of this relaxation (taurelax,-30 mV) remained
      unchanged (about 60 ms between 2 and 100 microM Ca2+o). 7. The data suggest that
      Ca2+o produces marked changes in the kinetics and single channel conductance of
      cation channels, which may account for the facilitatory effect of micromolar
      concentrations of Ca2+o on the peak amplitude of Icat.

PMID- 9769416
TI  - Facilitation of the presynaptic calcium current at an auditory synapse in rat
      brainstem.
AB  - 1. The presynaptic calcium current (IpCa) was recorded from the calyx of Held in
      rat brainstem slices using the whole-cell patch clamp technique. 2. Tetanic
      activation of IpCa by 1 ms depolarizing voltage steps markedly enhanced the
      amplitude of IpCa. Using a paired pulse protocol, the second (test) response was
      facilitated with inter-pulse intervals of less than 100 ms. The facilitation was
      greater at shorter intervals and was maximal (about 20%) at intervals of 5-10 ms.
      3. When the test pulse duration was extended, the facilitation was revealed as an
      increased rate of IpCa activation. From the current-voltage relationship measured
      at 1 ms from onset, facilitation could be described by a shift in the half
      activation voltage of about -4 mV. 4. IpCa facilitation was not attenuated when
      guanosine-5'-O-(3-thiotriphosphate) (GTPgammaS) or guanosine-5'-O-(2
      thiodiphosphate) (GDPbetaS) was included in the patch pipette, suggesting that G
      proteins are not involved in this phenomenon. 5. On reducing [Ca2+]o, the
      magnitude of facilitation diminished proportionally to the amplitude of IpCa.
      Replacement of [Ca2+]o by Ba2+ or Na+, or buffering of [Ca2+]i with EGTA or BAPTA
      attenuated IpCa facilitation. 6. We conclude that repetitive presynaptic activity
      can facilitate the presynaptic Ca2+ current through a Ca2+-dependent mechanism.
      This mechanism would be complementary to the action of residual Ca2+ on the
      exocytotic machinery in producing activity-dependent facilitation of synaptic
      responses.

PMID- 9769418
TI  - Inhibition of Ca2+-dependent K+ channels in rat carotid body type I cells by
      protein kinase C.
AB  - 1. Whole-cell patch clamp recordings were used to investigate the effects of
      protein kinase C (PKC) activation on K+ and Ca2+ currents in type I cells
      isolated from the rat carotid body. 2. Pretreatment of cells for 10 min at 37 C
      with 4alpha-phorbol 12,13-didecanoate (4alpha-PDD, 200 nM), a phorbol ester which
      does not activate PKC, did not affect K+ current density as compared with cells
      pretreated with vehicle alone. By contrast, identical pretreatment with 200 nM 12
      O-teradecanoylphorbol-13-acetate (TPA, a PKC activator) dramatically reduced K+
      current density in type I cells. This effect was prevented by co-incubation of
      cells with the PKC inhibitor bisindolylmaleimide (BIM, 3 microM). 3. The
      sensitivity of K+ currents to inhibition by 200 microM Cd2+ (indicative of the
      presence of Ca2+-dependent K+ channels) was markedly reduced in TPA-treated cells
      as compared with sham-treated cells, cells treated with 4alpha-PDD, and cells
      treated with both TPA and BIM. Cd2+-resistant K+ current densities were of
      similar magnitude in all four groups of cells, as were the input resistances
      determined over the voltage range -100 mV to -50 mV. 4. Ca2+ channel current
      density was not significantly different in type I cells pretreated with 200 nM
      4alpha-PDD as compared with cells treated with the same concentration of TPA. 5.
      The degree of inhibition of K+ currents caused by hypoxia (Po2 15-20 mmHg) was
      unaltered by pretreatment of cells with 3 microM BIM. 6. The resting membrane
      potential of cells pretreated with TPA was depolarized as compared with controls,
      and the Ca2+-dependent K+ channel inhibitor iberiotoxin (20 nM) failed to
      depolarize these cells further. 7. Our results suggest that activation of PKC
      causes a marked, selective inhibition of Ca2+-dependent K+ currents in type I
      carotid body cells, but that PKC activation is unlikely to account for inhibition
      of these channels by acute hypoxia.

PMID- 9769419
TI  - Regulation of murine cystic fibrosis transmembrane conductance regulator Cl-
      channels expressed in Chinese hamster ovary cells.
AB  - 1. We investigated the effect of protein kinases and phosphatases on murine
      cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels,
      expressed in Chinese hamster ovary (CHO) cells, using iodide efflux and the
      excised inside-out configuration of the patch-clamp technique. 2. The protein
      kinase C (PKC) activator, phorbol dibutyrate, enhanced cAMP-stimulated iodide
      efflux. However, PKC did not augment the single-channel activity of either human
      or murine CFTR Cl- channels that had previously been activated by protein kinase
      A. 3. Fluoride, a non-specific inhibitor of protein phosphatases, stimulated both
      human and murine CFTR Cl- channels. However, calyculin A, a potent inhibitor of
      protein phosphatases 1 and 2A, did not enhance cAMP-stimulated iodide efflux. 4.
      The alkaline phosphatase inhibitor, (-)-bromotetramisole augmented cAMP
      stimulated iodide efflux and, by itself, stimulated a larger efflux than that
      evoked by cAMP agonists. However, (+)-bromotetramisole, the inactive enantiomer,
      had the same effect. For murine CFTR, neither enantiomer enhanced single-channel
      activity. In contrast, both enantiomers increased the open probability (Po) of
      human CFTR, suggesting that bromotetramisole may promote the opening of human
      CFTR. 5. As murine CFTR had a low Po and was refractory to stimulation by
      activators of human CFTR, we investigated whether murine CFTR may open to a
      subconductance state. When single-channel records were filtered at 50 Hz, a very
      small subconductance state of murine CFTR was observed that had a Po greater than
      that of human CFTR. The occupancy of this subconductance state may explain the
      differences in channel regulation observed between human and murine CFTR.

PMID- 9769420
TI  - Activation of cAMP-dependent C1- currents in guinea-pig paneth cells without
      relevant evidence for CFTR expression.
AB  - 1. To determine whether Paneth cells exhibit functional expression of cAMP
      activated Cl- currents and molecular expression of the cystic fibrosis
      transmembrane conductance regulator (CFTR), we applied whole-cell patch clamp and
      single-cell mRNA analysis by reverse transcription (RT) followed by polymerase
      chain reaction (PCR) amplification to single Paneth cells in crypts isolated from
      the guinea-pig small intestine. 2. Prominent activation of Cl- currents was
      consistently observed after stimulation with dibutyryl cAMP and forskolin or with
      vasoactive intestinal polypeptide (VIP). The cAMP-activated Cl- current was
      inhibited by removal of intracellular ATP or administration of an inhibitor of
      protein kinase A. 3. Many of the biophysical and pharmacological properties of
      the currents were phenotypically similar to those of the CFTR Cl- channel, such
      as the ohmic current-voltage relationship, the anion selectivity with a Type III
      sequence (Br- > Cl- > I- >> F- >= gluconate-), I--induced blockage, insensitivity
      to a stilbene-derivative Cl- channel blocker, and sensitivity to a carboxylate
      analogue Cl- channel blocker. The sensitivity of the current to glibenclamide
      was, however, much weaker than that reported for the CFTR Cl- channel current. In
      contrast to the time independence of CFTR currents, the inward component of the
      Paneth cell Cl- currents exhibited inactivation kinetics. 4. Expression of CFTR
      mRNA could not be detected by RT-PCR analysis in almost all single Paneth cells,
      although its expression was consistently detected at the whole-crypt level. The
      presence of a small number of CFTR-expressing epithelial cells, which were
      scattered both in villi and crypts but not at the crypt base where Paneth cells
      were located, was demonstrated by immunocytochemistry. 5. Taken together, it
      appears that guinea-pig Paneth cells functionally express cAMP-activated Cl-
      conductance without relevant evidence for molecular expression of CFTR.
      Functional expression of VIP receptors in the Paneth cells was also demonstrated.

PMID- 9769421
TI  - Overexpression of nerve growth factor in the heart alters ion channel activity
      and beta-adrenergic signalling in an adult transgenic mouse.
AB  - 1. The electrophysiological and pharmacological properties of cardiac myocytes
      from the hearts of adult transgenic mice engineered to overexpress nerve growth
      factor (NGF) in the heart were studied. 2. There was a 12% increase in the
      ventricular myocyte capacitance in NGF myocytes consistent with cardiac
      hypertrophy, and action potential duration at 90% repolarization (APD90) was
      prolonged by 142 % compared with wild-type (WT) myocytes. This was due, at least
      in part, to a decrease in the density of two K+ currents, Ito and IK(ur), which
      were significantly reduced in NGF mice with no change in their
      electrophysiological characteristics. We found no change in the current density
      or electrophysiological properties of the L-type Ca2+ current. 3. The effect on
      Ito and IK(ur) of TEA and 4-aminopyridine (4-AP) was not different in cells
      isolated from WT and NGF mice. The prolongation of APD observed in NGF cells was
      mimicked in WT cells by exposure to 1 mM 4-AP, which partially blocked Ito,
      completely blocked IK(ur) and increased APD90 by 157%. 4. The isoprenaline
      induced increase in ICa was significantly smaller in NGF myocytes than in WT
      myocytes. This was not due to a decrease in beta-adrenergic receptor (beta-AR)
      density, as this was increased in NGF tissue by 55%. Analysis of beta-AR subtypes
      showed that this increase was entirely due to an increase in beta2-AR density
      with no change in beta1-ARs. 5. The response of the beta-AR-coupled adenylyl
      cyclase system to isoprenaline, Gpp(NH)p and forskolin was studied by measuring
      cAMP production. In NGF tissue, isoprenaline elicited a significantly smaller
      response than in WT myoyctes and this was not due to reduced adenylyl cyclase
      activity as the responses of NGF tissue to guanylylimidodiphosphate (Gpp(NH)p)
      and forskolin were unaffected. 6. In conclusion, the overexpression of NGF in the
      mouse heart resulted in a decrease in the current density of two K+ channels,
      which contributed to the prolongation of the cardiac action potential. Despite an
      increase in beta2-AR density in the hearts of the NGF mice, the response to
      isoprenaline was diminished, and this was due to an uncoupling of the beta-ARs
      from the intracellular signalling cascade. These potentially pathological changes
      may be involved in the occurrence of ventricular arrhythmias in cardiac
      hypertrophy and failure, and this mouse provides a novel model in which to study
      such changes.

PMID- 9769422
TI  - Synaptic inhibition: its role in suprachiasmatic nucleus neuronal
      thermosensitivity and temperature compensation in the rat.
AB  - 1. Whole-cell patch clamp recordings of neurones in the suprachiasmatic nucleus
      (SCN) from rat brain slices were analysed for changes in spontaneous synaptic
      activity during changes in temperature. While recent studies have identified
      temperature-sensitive responses in some SCN neurones, it is not known whether or
      how thermal information can be communicated through SCN neural networks,
      particularly since biological clocks such as the SCN are assumed to be
      temperature compensated. 2. Synaptic activity was predominantly inhibitory and
      mediated through GABAA receptor activation. Spontaneous inhibitory postsynaptic
      potentials (IPSPs) and currents (IPSCs) were usually blocked with perifusion of
      10-50 microM bicuculline methiodide (BMI). BMI was used to test hypotheses that
      inhibitory synapses are capable of either enhancing or suppressing the
      thermosensitivity of SCN neurones. 3. Temperature had opposite effects on the
      amplitude of IPSPs and IPSCs. Warming decreased IPSP amplitude but increased IPSC
      amplitude. This suggests that thermally induced changes in IPSP amplitude are
      primarily influenced by resistance changes in the postsynaptic membrane. The
      thermal effect on IPSP amplitude contributed to an enhancement of
      thermosensitivity in some neurones. 4. In many SCN neurones, temperature affected
      the frequency of IPSPs and IPSCs. An increase in IPSP frequency with warming and
      a decrease in frequency during cooling made several SCN neurones temperature
      insensitive, allowing these neurones to maintain a relatively constant firing
      rate during changes in temperature. This temperature-adjusted change in synaptic
      frequency provides a mechanism of temperature compensation in the rat SCN.

PMID- 9769423
TI  - Persistent depolarizing action of GABA in rat Cajal-Retzius cells.
AB  - 1. To characterize membrane properties that might be relevant to the function and
      fate of Cajal-Retzius (CR) cells, the pharmacological and physiological effects
      of GABA acting at GABAA receptors were studied in CR cells from embryonic (E18)
      and postnatal (P11-13) slices of rat neocortex. 2. From the embryonic to the
      postnatal stage, GABA-induced maximum current almost tripled, the EC50 increased
      from 38 to 74 microM, and the Hill number increased from 1.4 to 1.9. Muscimol
      elicited currents were qualitatively and quantitatively similar to those produced
      by GABA. 3. GABA-induced changes in the amplitude of large-conductance Ca2+
      activated K+ channel current recorded on-cell from E18 CR cells were consistent
      with depolarization. 4. GABA-mediated depolarization of embryonic and postnatal
      CR cells was studied directly with perforated-patch recording techniques. Ten
      micromolar and 1 mM GABA, respectively, depolarized E18 CR cells to -27 +/- 1 and
      -25 +/- 3 mV. These same concentrations of GABA depolarized P11 CR cells to -36
      +/- 3 and -23 +/- 3 mV. 5. In postnatal cortex, GABA (100 microM) increased the
      firing rate of CR cells 7.3-fold. By contrast, the firing of hippocampal
      pyramidal cells from slices of the same age (P12) was totally and reversibly
      blocked by GABA. 6. These experiments suggest that contrary to its postnatal
      inhibitory shift observed in other cells, the depolarizing effect of GABA remains
      in CR cells from E18 until their virtual disappearance.

PMID- 9769424
TI  - Excitation-induced force recovery in potassium-inhibited rat soleus muscle.
AB  - 1. Excitation markedly stimulates the Na+-K+ pump in skeletal muscle. The effect
      of this stimulation on contractility was examined in rat soleus muscles exposed
      to high extracellular K+ concentration ([K+]o). 2. At a [K+]o of 10 mM, tetanic
      force declined to 58 % of the force in standard buffer with 5.9 mM K+. Subsequent
      direct stimulation of the muscle at 1 min intervals with 30 Hz pulse trains of 2
      s duration induced a 97 % recovery of force within 14 min. Force recovery could
      also be elicited by stimulation via the nerve. In muscles exposed to 12.5 mM K+,
      30 Hz pulse trains of 2 s duration at 1 min intervals induced a recovery of force
      from 16 +/- 2 to 62 +/- 4% of the initial control force at a [K+]o of 5.9 mM. 3.
      The recovery of force was associated with a decrease in intracellular Na+ and was
      blocked by ouabain. This indicates that the force recovery was secondary to
      activation of the Na+-K+ pump. 4. Excitation stimulates the release of calcitonin
      gene-related peptide (CGRP) from nerves in the muscle. Since CGRP stimulates the
      Na+-K+ pump, this may contribute to the excitation-induced force recovery.
      Indeed, reducing CGRP content by capsaicin pre-treatment or prior denervation
      prevented both the excitation-induced force recovery and the drop in
      intracellular Na+. 5. The data suggest that activation of the Na+-K+ pump in
      contracting muscles counterbalances the depressing effect of reductions in the
      chemical gradients for Na+ and K+ on excitability.

PMID- 9769425
TI  - The contribution of pH-dependent mechanisms to fatigue at different intensities
      in mammalian single muscle fibres.
AB  - 1. The contribution of intracellular pH (pHi) to the failure of Ca2+ release and
      inhibition of contractile proteins observed during fatigue was assessed in single
      intact mouse muscle fibres at 22 C. Fatigue was induced by repeated tetani at
      intensities designed to induce different levels of intracellular acidosis. Force
      and either intracellular free Ca2+ concentration ([Ca2+]i; measured using indo-1)
      or pHi (measured using SNARF-1) were recorded in fibres fatigued at two different
      intensities. 2. Intensity was varied by the repetition rate of tetani and
      quantified by the duty cycle (the fraction of time when the muscle was
      tetanized). Stimulation at the low intensity (duty cycle approximately 0.1)
      reduced force to 30 % of initial values in 206 +/- 21 s (60 +/- 7 tetani); at the
      high intensity (duty cycle approximately 0.3) force was reduced to 30% in 42 +/-
      7 s (43 +/- 7 tetani) (P < 0.05; n = 14). 3. When force was reduced to 30 % of
      initial values, tetanic [Ca2+]i had fallen from 648 +/- 87 to 336 +/- 64 nM (48%
      decrease) at the low intensity but had only fallen from 722 +/- 84 to 468 +/- 60
      nM (35% decrease) at the higher intensity (P < 0.05 low vs. high intensity; n =
      7). 4. Fatigue resulted in reductions in Ca2+ sensitivity of the contractile
      proteins which were greater at the high intensity (pre-fatigue [Ca2+]i required
      for 50 % of maximum force (Ca50) = 354 +/- 23 nM; post-fatigue Ca50 = 421 +/- 48
      nM and 524 +/- 43 nM for low and high intensities, respectively). Reductions in
      maximum Ca2+-activated force (Fmax) were similar at the two intensities (pre
      fatigue Fmax = 328 +/- 22 microN; post-fatigue Fmax = 271 +/- 20 and 265 +/- 19
      microN for low and high intensities, respectively). 5. Resting pHi was 7.15 +/-
      0.05. During fatigue at the low intensity, pHi was reduced by 0.12 +/- 0.02 pH
      units and at the high intensity pHi was reduced by 0.34 +/- 0.07 pH units (P <
      0.05; n = 5). 6. Our results indicate that the more rapid fall in force at a high
      intensity is due to a reduction in Ca2+ sensitivity of the contractile proteins,
      probably related to the greater acidosis. Our data also indicate that the failure
      of Ca2+ release and reduced maximum Ca2+-activated force observed during fatigue
      are not due to reductions in intracellular pH.

PMID- 9769426
TI  - Presynaptic adrenergic facilitation of parasympathetic neurotransmission in
      sympathectomized rat smooth muscle.
AB  - 1. Parasympathetic innervation of rat eyelid tarsal smooth muscle normally
      inhibits sympathetic neurotransmission prejunctionally without significant direct
      postjunctional effects. Following surgical sympathectomy, parasympathetic
      stimulation elicits smooth muscle contraction. This study examined the relative
      contributions of cholinergic and adrenergic mechanisms mediating these
      contractions. 2. Electrical stimulation of the superior salivatory nucleus, which
      activates tarsal muscle parasympathetic nerves, elicited large contractions at 2
      days postsympathectomy, which were abolished by atropine and were decreased by 65
      % by alpha1-adrenoceptor blockade or spinal cord transection. 3. Contractions in
      response to direct cholinergic stimulation by bethanechol at 2 days
      postsympathectomy were increased following spinal cord transection (C2) and
      suppressed by the alpha1-adrenoceptor agonist phenylephrine, indicating that
      adrenoceptors on smooth muscle attenuate cholinergic contractions. However,
      phenylephrine infusion enhanced contractile responses to parasympathetic
      stimulation. 4. Reverse transcription-polymerase chain reaction revealed alpha1D
      adrenoceptor mRNA within pterygopalatine ganglia. 5. At 5 weeks and 14 months
      postsympathectomy, adrenergic facilitation was significantly less than at 2 days,
      whereas prazosin-insensitive muscarinic contraction was increased. 6. We conclude
      that degeneration of sympathetic innervation is followed rapidly by adrenoceptor
      mediated prejunctional enhancement of parasympathetic nerve-smooth muscle
      neurotransmission, which occurs prior to neuroeffector junction formation as
      determined previously by electron microscopy. Subsequently, noradrenergic
      enhancement is diminished as cholinergic neurotransmission becomes established.

PMID- 9769428
TI  - Medullary raphe neurones and baroreceptor modulation of the respiratory motor
      pattern in the cat.
AB  - 1. Perturbations of arterial blood pressure change medullary raphe neurone
      activity and the respiratory motor pattern. This study sought evidence for
      actions of baroresponsive raphe neurones on the medullary respiratory network. 2.
      Blood pressure was perturbed by intravenous injection of an alpha1-adrenergic
      receptor agonist, unilateral pressure changes in the carotid sinus, or occlusion
      of the descending aorta in thirty-six Dial-urethane-anaesthetized, vagotomized,
      paralysed, artificially ventilated cats. Neurones were monitored with
      microelectrode arrays in two or three of the following domains: nucleus raphe
      obscurus-nucleus raphe pallidus, nucleus raphe magnus, and rostral and caudal
      ventrolateral medulla. Data were analysed with cycle-triggered histograms,
      peristimulus time and cumulative sum histograms, cross-correlograms and spike
      triggered averages of efferent phrenic nerve activity. 3. Prolongation of the
      expiratory phase and decreased peak integrated phrenic amplitude were most
      frequently observed. Of 707 neurones studied, 310 had altered firing rates during
      stimulation; changes in opposite directions were monitored simultaneously in
      fifty-six of eighty-seven data sets with at least two baroresponsive neurones. 4.
      Short time scale correlations were detected between neurones in 347 of 3388
      pairs. Seventeen pairs of baroresponsive raphe neurones exhibited significant
      offset correlogram features indicative of paucisynaptic interactions. In
      correlated raphe-ventrolateral medullary neurone pairs with at least one
      baroresponsive neurone, six of seven ventrolateral medullary decrementing
      expiratory (E-Decr) neurones increased their firing rate during baroreceptor
      stimulation. Thirteen of fifteen ventrolateral medullary inspiratory neurones
      correlated with raphe cells decreased their firing rate during baroreceptor
      stimulation. 5. The results support the hypothesis that raphe neuronal assemblies
      transform and transmit information from baroreceptors to neurones in the ventral
      respiratory group. The inferred actions both limit and promote responses to
      sensory perturbations and match predictions from simulations of the respiratory
      network.

PMID- 9769427
TI  - Multiple ionic mechanisms mediate inhibition of rat motoneurones by inhalation
      anaesthetics.
AB  - 1. We studied the effects of inhalation anaesthetics on the membrane properties
      of hypoglossal motoneurones in a neonatal rat brainstem slice preparation. 2. In
      current clamp, halothane caused a membrane hyperpolarization that was invariably
      associated with decreased input resistance; in voltage clamp, halothane induced
      an outward current and increased input conductance. Qualitatively similar results
      were obtained with isoflurane and sevoflurane. 3. The halothane current reversed
      near the predicted K+ equilibrium potential (EK) and was reduced in elevated
      extracellular K+ and in the presence of Ba2+ (2 mM). Moreover, the Ba2+-sensitive
      component of halothane current was linear and reversed near EK. The halothane
      current was not sensitive to glibenclamide or thyrotropin-releasing hormone
      (TRH). Therefore, the halothane current was mediated, in part, by activation of a
      Ba2+-sensitive K+ current distinct from the ATP- and neurotransmitter-sensitive
      K+ currents in hypoglossal motoneurones. 4. Halothane also inhibited Ih, a
      hyperpolarization-activated cationic current; this was primarily due to a
      decrease in the absolute amount of current, although halothane also caused a
      small, but statistically significant, shift in the voltage dependence of Ih
      activation. Extracellular Cs+ (3 mM) blocked Ih and a component of halothane
      sensitive current with properties reminiscent of Ih. 5. A small component of
      halothane current, resistant to Ba2+ and Cs+, was observed in TTX-containing
      solutions at potentials depolarized to approximately -70 mV. Partial Na+
      substitution by N-methyl-D-glucamine completely abolished this residual current,
      indicating that halothane also inhibited a TTX-resistant Na+ current active near
      rest potentials. 6. Thus, halothane activates a Ba2+-sensitive, relatively
      voltage-independent K+ current and inhibits both Ih and a TTX-insensitive
      persistent Na+ current in hypoglossal motoneurones. These effects of halothane
      decrease motoneuronal excitability and may contribute to the immobilization that
      accompanies inhalation anaesthesia.

PMID- 9769429
TI  - Efferent projection from the preoptic area for the control of non-shivering
      thermogenesis in rats.
AB  - 1. To investigate the characteristics of efferent projections from the preoptic
      area for the control of non-shivering thermogenesis, we tested the effects of
      thermal or chemical stimulation, and transections of the preoptic area on the
      activity of interscapular brown adipose tissue in cold-acclimated and non
      acclimated anaesthetized rats. 2. Electrical stimulation of the ventromedial
      hypothalamic nucleus (VMH) elicited non-shivering thermogenesis in the brown
      adipose tissue (BAT); warming the preoptic area to 41.5 C completely suppressed
      the thermogenic response. 3. Injections of d, l-homocysteic acid (DLH; 0.5 mM,
      0.3 microliter) into the preoptic area also significantly attenuated BAT
      thermogenesis, whereas injections of control vehicle had no effect. 4.
      Transections of the whole hypothalamus in the coronal plane at the level of the
      paraventricular nucleus induced rapid and large rises in BAT and rectal
      temperatures. This response was not blocked by pretreatment with indomethacin.
      The high rectal and BAT temperatures were sustained more than 1 h, till the end
      of the experiment. Bilateral knife cuts that included the medial forebrain bundle
      but not the paraventricular nuclei elicited similar rises in BAT and rectal
      temperatures. Medial knife cuts had no effect. 5. These results suggest that warm
      sensitive neurones in the preoptic area contribute a larger efferent signal for
      non-shivering thermogenesis than do cold-sensitive neurones, and that the
      preoptic area contributes a tonic inhibitory input to loci involved with non
      shivering thermogenesis. This efferent inhibitory signal passes via lateral, but
      not medial, hypothalamic pathways.

PMID- 9769430
TI  - Nitric oxide modulates cholinergic reflex pathways to the longitudinal and
      circular muscle in the isolated guinea-pig distal colon.
AB  - 1. The involvement of nitric oxide (NO) in enteric neural pathways underlying
      reflex responses of the longitudinal muscle (LM) and circular muscle (CM) layers
      activated by mucosal stimulation was examined in the isolated guinea-pig distal
      colon. 2. A segment of colon spanned two partitions (10 mm apart), which divided
      the organ bath into three chambers: a recording chamber where LM and CM tension
      was measured; a stimulation chamber where mucosal stimulation was applied; and a
      middle chamber separating them. 3. Brushing the mucosa anal and oral to the
      recording site evoked simultaneous oral contraction and anal relaxation of both
      the LM and CM. 4. N omega-nitro-L-argininel-NA; 100 microM) or N omega-nitro-L
      arginine methyl ester (L-NAME; 100 microM) applied to the middle chamber or
      stimulation chamber decreased the oral contractile response of the LM and CM (by
      about 30-40 %), but increased the anal relaxation (> 600 %) and exposed an anal
      contraction (> 1000 % increase) of both muscles. The addition of L-NA to the
      recording chamber reduced the anal relaxation of the LM and CM and the anal
      contraction of the LM, but slightly increased the anal contraction of the CM. 5.
      S-Nitroso-N-acetylpenicillamine (SNAP; 10 microM), an NO donor, reversed the
      effects of L-NA in the middle or stimulation chambers. 6. 1H-[1,2,4]oxadiazolo[4,
      3-a]quinoxalin-1-one (ODQ; 10 microM), a soluble guanylate cyclase inhibitor,
      mimicked the effects of L-NAin the middle chamber or stimulation chamber, but
      these effects were not reversed by SNAP. 7. The oral contractile responses, and
      the anal relaxation and contractile responses of the LM and CM produced by L-NA
      in the stimulation or middle chambers, were blocked by hexamethonium (300 microM)
      in any chamber. Atropine (1 microM) in the recording chamber reduced the
      contractile responses of the LM and CM. 8. In conclusion, endogenous NO
      facilitates and depresses release of acetylcholine from interneurons in ascending
      and descending nervous pathways, respectively. These NO effects are mediated
      through soluble guanylate cyclase in cholinergic interneurons

PMID- 9769431
TI  - An in vitro study of the properties of vagal afferent fibres innervating the
      ferret oesophagus and stomach.
AB  - 1. A novel preparation of the oesophagus with attached vagus nerve from the
      ferret maintained in vitro was used to study the properties of single vagal
      afferent nerve fibres with identified receptive fields. 2. Recordings were made
      from three types of gastro-oesophageal vagal afferent fibres that were classified
      on the basis of their sensitivity to mechanical stimulation. There were those
      responding to mucosal stroking (mucosal receptors), to circular tension (tension
      receptors) and those responding to mucosal stroking and circular tension, which
      we have termed tension/mucosal (TM) receptors. 3. The conduction velocities for
      mucosal, TM and tension receptor fibres were 6.38 +/- 1.22 m s-1 (n = 22), 6.20
      +/- 1.49 m s-1 (n = 13) and 5.33 +/- 0.86 m s-1 (n = 22), respectively. 4.
      Receptive fields of afferents showed random topographical distribution by fibre
      type and conduction velocity. They were found mainly distal but also occasionally
      proximal to the point of vagal dissection. 5. Twenty-eight per cent of mucosal,
      63% of TM and 43% of tension receptors responded to one or more drugs or chemical
      stimuli applied to the receptive field. 6. In conclusion, this experimental
      preparation provides evidence for the existence of three types of oesophageal
      vagal afferent fibre, namely mucosal, tension and the newly identified
      tension/mucosal receptors.

PMID- 9769432
TI  - The compliance of the porcine pulmonary artery depends on pressure and heart
      rate.
AB  - 1. The influence of mean pulmonary arterial pressure (mean Ppa) on dynamic (Cd)
      and pseudo-static compliance (Cps) of the pulmonary artery was studied at a
      constant and a changing heart rate. Cd is the change in cross-sectional area
      (CSA) relative to the change in Ppa throughout a heart cycle. Cps is the change
      in mean CSA relative to the change in mean Ppa. If Cd is known, pulmonary blood
      flow can be computed from the Ppa using a windkessel model. We investigated
      whether Cps can be interchanged with Cd. 2. In nine anaesthetized pigs, we
      determined the mean CSA and Cd of the pulmonary artery at various Ppa levels,
      ranging from approximately 30 to 10 mmHg, established by bleeding. Two series of
      measurements were carried out, one series at a spontaneously changing heart rate
      (n = 9) and one series at a constant heart rate (n = 6). To determine CSA a
      conductance method was used. 3. Cps depended on pressure. The mean CSA versus
      mean Ppa curves were sigmoid and steepest in the series with the increasing heart
      rate (established by bleeding). The CSA versus Ppa loop during a heart cycle,
      giving Cd, was approximately linear and almost closed. The Cd versus mean Ppa
      relationship was bell shaped. Its width was smaller if the heart rate increased
      during the series of measurements. The pressure, where Cd was maximum, was higher
      at higher heart rates. Furthermore, the maximum Cd was not affected by the heart
      rate. 4. Because the pulmonary artery constricts with increasing heart rate, Cps
      will be overestimated during procedures where heart rate increases. Cd should be
      determined on a beat-to-beat basis to calculate flow because it changes with mean
      pulmonary arterial pressure and heart rate.

PMID- 9769442
TI  - The stages of Alzheimer's disease: a reappraisal.
AB  - 'Stages', as used in clinical practice and research, are defined, their value
      described, and criteria are proposed for their evaluation. The specific interest
      is in staging Alzheimer's disease (AD). Two staging systems, one based on the
      Global Deterioration Scale (GDS) and one based on the Mini-Mental State Exam
      (MMSE), are compared in terms of these criteria, as an illustration of the
      process involved. We propose that there is not one unique staging system, that
      different staging criteria might be appropriate to different research or clinical
      needs, depending on which part of the temporal course of the disease is of
      primary interest, and on whether the focus is on cognitive, functional,
      neurological, behavioral, economic, or other issues. GDS staging seems a better
      choice for the later stages of AD when the focus is on functional change. MMSE
      staging seems a better choice for tracking the earlier stages of AD when the
      focus is on cognitive change.

PMID- 9769433
TI  - Enhanced vasoconstrictor responses in renal and femoral arteries of the golden
      hamster during hibernation.
AB  - 1. The present study assessed local regulation of vascular tone of euthermic
      (control), cold control and hibernating golden hamsters. Sympathetic
      neurotransmission in the renal artery, the long term effects of hibernation on
      perivascular nerve activity, and the responsiveness of femoral artery to a number
      of neurotransmitters and hormones with both constrictor and dilator actions
      during hibernation are described. 2. The contractile responses of the renal
      arterial rings to transmural nerve stimulation (80 V, 0.1 ms, 4-64 Hz, for 1 s)
      were negligible in controls, significantly increased at higher frequencies of
      stimulation in cold controls and markedly enhanced in the hibernating group at
      all frequencies tested. The contractile responses to exogenous noradrenaline (NA;
      0.1-100 microM) were significantly increased in the renal arteries of hibernating
      hamsters compared with controls, but not compared with cold controls. Responses
      to exogenous ATP (1-3000 microM) and KCl (120 mM) were similar among all
      experimental groups. 3. The maximal contractile responses of femoral arterial
      rings to the sympathetic co-transmitter ATP and 5-hydroxytryptamine were
      increased by approximately 124% and 99%, respectively, in hibernating compared
      with cold control preparations without a change in the concentration of agonist
      that produces half-maximal response. However, the responses to NA were not
      altered during hibernation. 4. Vasoconstriction of femoral arterial rings in
      response to arginine vasopressin was significantly enhanced in both cold controls
      and hibernating groups, while vasoconstriction in response to endothelin-1 and
      KCl was unaltered. 5. The dilator responses of femoral arterial rings to
      acetylcholine, sodium nitroprusside and adenosine were not different among the
      groups. 6. It is suggested that the marked augmentation of sympathetic
      neurotransmission, selective supersensitivity of the vascular smooth muscle to
      sympathetic contractile agents and unaltered vasodilatory mechanisms may provide
      a means for maintenance of vascular tone and peripheral resistance during
      hibernation.

PMID- 9769443
TI  - In vivo quantification of brain volumes in subcortical vascular dementia and
      Alzheimer's disease. An MRI-based study.
AB  - Quantitative magnetic resonance imaging (MRI) was used to assess global and
      regional cerebral volumes in patients with a clinical diagnosis of subcortical
      vascular dementia (VD) and Alzheimer's disease (AD). Whole brain volume,
      cerebrospinal fluid volume, volumes of the temporal, frontal and parietal lobes,
      the cerebellum and the amygdala-hippocampus complex were determined using a
      personal computer-based software. Seventeen patients with VD, 22 patients with AD
      and 13 healthy controls were included. Analysis of covariance using age as
      covariate demonstrated significant mean differences between controls and dementia
      groups with respect to all morphological parameters. However, apart from the
      volume of the cerebellum no significant volumetric differences were found between
      VD and AD. These results indicate that MRI-based volumetry allows differentiation
      between AD or VD from normal controls and that measurement of cerebellar volume
      may be of use to separate vascular and degenerative dementia. However, since the
      distribution of cerebral atrophy in both dementia groups is very similar, it is
      suggested that the atrophic changes are not specific to the underlying cause but
      rather reflect the selective vulnerability of neuronal structures.

PMID- 9769445
TI  - Prevalence of Alzheimer's disease and other dementing disorders: Assiut-Upper
      Egypt study.
AB  - The aim of this study was to determine the prevalence rate of Alzheimer's disease
      (AD) and other types of dementias among the population over the age of 60 years
      in Assiut governorate. A 3-phase cross-sectional population-based study was
      carried out to screen 2, 000 subjects residing in 11 different locations
      representing the sociocultural status of the area. We subjected each proband to a
      modified form of the Mini Mental State Examination test. Subjects scored 21 or
      less were investigated according to a standardized protocol. We found 90 demented
      subjects yielding a crude prevalence ratio (case per 100 population over the age
      of 60) of 4.5. A diagnosis of subtypes of dementia was reached in 83 cases.
      Prevalence ratios for dementia subtypes were 2.2 for AD, 0.95 for multi-infarct
      dementia. 0.55 for mixed dementias and 0.45 for secondary dementias. Age-specific
      prevalence tends to be doubled every 5 years. Occupation, level of education and
      residence did not affect the prevalence or severity of dementia. Comparison with
      other studies suggests that dementia of all types is as frequent in Assiut
      governorate as elsewhere.

PMID- 9769444
TI  - Relatively preserved hippocampal glucose metabolism in mild Alzheimer's disease.
AB  - The purpose of this study was to clarify the changes in hippocampal glucose
      metabolism in mild Alzheimer's disease (AD) using positron emission tomography
      (PET) and 2-(18F)fluoro-2-deoxy-D-glucose (FDG). Forty-one patients with probable
      mild AD (age: 69.0 +/- 8.0 years; MMSE: 22.6 +/- 2.1) and 22 normal volunteers
      (age: 67.7 +/- 7.1 years) were studied. The regional cerebral metabolic rate for
      glucose (CMRglc) was measured using FDG and PET. Although the mean CMRglc in the
      parietal region was significantly lower in the AD group (right: 6.35 +/- 1.26
      mg/100 g/min; left: 6.37 +/- 1.21 mg/100 g/min) than in the control group (right:
      7.73 +/- 1.02 mg/100 g/min; left: 7.63 +/- 0.95 mg/100 g/min), the mean CMRglc in
      the hippocampus did not show a significant difference between the AD group
      (right: 4.58 +/- 0.70 mg/100 g/min; left: 4.63 +/- 0.67 mg/100 g/min) and the
      control group (right: 5.22 +/- 0.65 mg/100 g/min; left: 5.22 +/- 0.67 mg/100
      g/min) by analysis of variance and post-hoc Tukey's test. The magnitude of the
      hippocampal CMRglc reduction was not as large as that of parietal CMRglc
      reduction. Statistical parametric maps (SPM) analysis also did not significantly
      demonstrate reduced hippocampal CMRglc in AD patients, although it did show a
      significant reduction in parietal CMRglc in AD patients. Hippocampal CMRglc was
      not significantly decreased in mild AD. This was unexpected in view of previous
      studies that have shown atrophy and clinical dysfunction concerning hippocampus
      in AD, and suggests that the pathophysiology of the hippocampus in AD may be more
      complex than was previously thought.

PMID- 9769446
TI  - Epidemiological dementia index: a screening instrument for Alzheimer's disease
      and other types of dementia suitable for use in populations with low education
      level.
AB  - INTRODUCTION: MMSE and CAMCOG are neuropsychological scales developed for use in
      everyday clinical practice and epidemiological surveys. MATERIAL AND METHODS:
      These two instruments were used as part of the assessment during an
      epidemiological survey in the municipality of Pylaia, Greece. The project was
      based on the World Health Organization Program for Research on Aging and Age
      Associated Dementias (1992). It had two phases. During phase I, nursing students
      collected demographic data, risk factors, personal and family history data and
      they applied MMSE, CAMCOG and scales of everyday life functioning. During phase
      II, 4 physicians examined all subjects that manifested possible cognitive
      deterioration (MMSE<27), in order to reach a final diagnosis. The final diagnosis
      was made according to DSM-IV and NINCDS-ADRDA criteria. MMSE and CAMCOG were not
      taken into consideration in the diagnostic process. Three hundred and eighty
      subjects were initially screened. All were aged over 70 years. After the
      exclusion of subjects who were illiterate, blind, etc., the results of 277
      subjects were finally analyzed. Subjects with 6 years of education or less
      accounted for 92.42% of the total study sample. Twelve of them (5.33%) suffered
      from Alzheimer's disease, 7 from vascular dementia (2.52%) and 1 suffered from
      secondary dementia (0.36%). RESULTS: MMSE exceeded 90% sensitivity at the level
      22/23 and specificity at 14/15. The levels for CAMCOG were 56/57 and 43/44,
      respectively. This low performance of both tests is to a large extent due to the
      functional illiteracy of elderly individuals in Greece, to possible coexistence
      of mood disorders or simply to lack of cooperation. The analysis of data led to
      the development of an Epidemiological Dementia Index (EDI), with a scale ranging
      from 0 to 7. Nondemented subjects had a mean EDI of 5.12 (SD = 1.67) and demented
      patients had a mean EDI of 1.6 (SD = 1. 92). At the level 4/5 sensitivity was
      93.33. Specificity was 93.56 at the level 2/3.

PMID- 9769447
TI  - Validation of the full and short forms of the CAMDEX interview for diagnosing
      dementia: evidence from a one-year follow-up study.
AB  - The sensitivity and specificity of the two forms of the CAMDEX interview for
      dementia diagnosis were assessed in a 1-year follow-up study. At the beginning of
      the study, 60 patients (22 males and 38 females) who met DSM-IV criteria for
      dementia and 60 matched controls (15 males and 45 females), were administered the
      short form of the CAMDEX (short CAMDEX) 3 months after the full one (full
      CAMDEX). At the follow-up, all patients were administered both the full and short
      CAMDEX (again with a 3-month interval), whereas controls were administered either
      CAMDEX form (in any case, at a 12-month interval from initial testing). Upon
      initial testing, the sensitivity of the full CAMCOG proved to be significantly
      higher than that of the short CAMCOG, while the opposite trend was observed for
      specificity, that is the sensitivity of the full Organicity was lower than that
      of the short Organicity, with specificity remaining equal in the two forms. Upon
      follow-up, the specificity and sensitivity levels of the two forms did not
      significantly differ for the CAMCOG and Organicity indices. Moreover, in
      detecting mildly demented patients, the full CAMCOG proved to be more accurate
      than the short one, while the opposite trend was observed for Organicity. Among
      the dementia subjects, significant correlations were found between the homologous
      indices of the two forms for both test sessions. On the whole, the short CAMDEX
      appears to maintain most of the psychometric properties of the full version and
      therefore the two CAMDEX forms can be considered to be interchangeable.

PMID- 9769448
TI  - Comorbidity and drug use in cognitively impaired elderly living in long-term
      care.
AB  - Cognitive impairment is associated with an increased mortality in older people.
      The prevalence and impact of comorbidity on functional status and mortality of
      demented patients has not been fully elucidated. Using a population-based data
      set, we describe the prevalence of cognitive impairment, functional status,
      principal comorbid conditions and 1-year survival for over 300,000 patients
      admitted to the nursing homes in five US states. Sixty-one percent of patients
      have some level of cognitive impairment, and this correlates with the degree of
      physical frailty. Severer cognitive impairment is associated with a higher
      mortality rate. Yet, patients with cognitive impairment appear to have fewer
      comorbid conditions and are less likely to receive medications and special
      treatments than residents with normal cognitive status. Additional studies are
      needed to understand whether demented patients may paradoxically be considered
      healthier or, instead, are only neglected.

PMID- 9769472
TI  - Expression of the MCP-1 gene and the HPV 16 E6/E7 oncogenes in squamous cell
      carcinomas of the cervix uteri and metastases.
AB  - Monocyte chemoattractant protein 1 (MCP-1) plays an important role in the
      recruitment of monocytes in solid tumors. Previously, for cervical carcinoma cell
      lines an inverse correlation between the expression of the MCP-1 gene and the
      human papillomavirus (HPV) oncogenes E6/E7 was described. In this study paraffin
      embedded biopsy specimens from 25 squamous cell carcinomas of the cervix uteri
      were analyzed for the expression of the MCP-1 gene and the HPV 16 E6/E7 oncogenes
      by RNA/RNA in situ hybridization. Similar to in vitro analyses, in our material a
      negative correlation between the transcription of these genes in tumor cells
      could be demonstrated in 19/25 cases, whereas in 6 cases both MCP-1 gene and HPV
      oncogene transcription could be detected. Interestingly, the same results
      regarding MCP-1 gene and HPV oncogene expression were observed in the majority of
      corresponding metastases. On the other hand, in stromal cells MCP-1-specific
      transcripts could be detected in all cases. In most of them intra- and/or
      peritumoral macrophages were observed. Our findings support the hypothesis that
      HPV oncoproteins are negative regulators of MCP-1 transcription.

PMID- 9769471
TI  - Human psoriatic skin in organ culture: comparison with normal skin exposed to
      exogenous growth factors and effects of an antibody to the EGF receptor.
AB  - Organ cultures were established from psoriatic lesional skin of 24 different
      individuals and maintained for 8 days under serum-free, growth-factor-free
      conditions. Nonlesional skin from 14 of the same individuals and normal skin from
      another 12 individuals were also maintained in organ culture. At the end of the
      incubation period, the tissues were fixed in formalin and examined
      histologically. Lesional skin continued to express features of psoriatic plaque,
      which included irregularly shaped epithelial cells arranged in a disorganized
      fashion, and elongation of the rete ridges with a thickening in their lower
      portion. Abnormal epidermal differentiation and separation of the upper epidermal
      layers from the lower layers was also a consistent feature. In contrast,
      nonlesional skin from psoriatic patients exhibited a histological appearance
      which resembled that of site-matched normal skin. When normal skin was exposed to
      a growth-factor-enriched culture medium during the 8-day incubation period, it
      exhibited a histological appearance similar to that of psoriatic skin. In
      addition to abnormal histological features, the psoriatic skin in organ culture
      released higher amounts of matrix metalloproteinase-9 (MMP-9; 92-kD gelatinase
      B/type IV collagenase) into the culture fluid than either nonlesional skin or
      normal skin. Organ cultures of psoriatic lesional skin from 6 individuals were
      maintained for 8 days in the presence of an antibody to the human epidermal
      growth-factor (EGF) receptor. The abnormal histological features of the psoriatic
      tissue were partially ameliorated in the presence of the antibody. These data
      suggest that growth factors which act through the EGF receptor help to maintain
      the psoriatic phenotype in organ culture. They also suggest that organ culture
      may provide a useful tool with which to elucidate the pathophysiological
      mechanisms of altered keratinocyte proliferation and differentiation in
      psoriasis.

PMID- 9769473
TI  - Detection of alterations in chromosomes 16 and 1 by fluorescence in situ
      hybridization in breast tumors cytologically or histologically equivocal for
      malignancy.
AB  - Structural and numerical alterations, and fusion of chromosomes 16 and 1 have
      been shown to occur frequently in low-grade breast carcinoma, but not in benign
      papilloma by fluorescence in situ hybridization (FISH). We carried out FISH
      analysis of 11 benign tumors and 3 breast tumors for which the preoperative
      diagnosis was equivocal for cancer. In 11 benign lesions and 1 benign phyllode
      tumor which was cytologically equivocal for malignancy, alteration of the
      chromosome 16 or 1 signal was not detected as a predominant cell clone. On the
      other hand, in 1 grade 1 invasive ductal carcinoma which was judged as equivocal
      for malignancy and 1 marked adenosis with atypia which was judged as malignant by
      fine-needle aspiration cytology, the majority of constituent tumor cells showed
      fusion of chromosomes 16 and 1. Detection of alterations in chromosomes 16 and 1
      as a predominant clone was suggested to be an indicator of lesion malignancy even
      though the grade of malignancy may not be high. As a supportive diagnostic
      procedure, FISH analysis may give information about the nature of lesions, when
      the lesions are clinically or pathologically equivocal for cancer.

PMID- 9769474
TI  - Expression of VCAM-1 in lymphocytes during the process of apoptosis.
AB  - The administration of corticosteroids induced apoptosis of thymocytes in vivo.
      Among various adhesion molecules examined, vascular cell adhesion molecule-1
      (VCAM-1, CD106) was shown to be strongly expressed in these apoptotic cells. Flow
      cytometric analysis also showed the expression of VCAM-1 in apoptotic thymocytes.
      An RT-PCR study demonstrated the expression of VCAM-1 mRNA in thymocytes. Splenic
      lymphocytes and other lymphoid cell lines also expressed VCAM-1 during the
      process of apoptosis. VCAM-1 mRNA expression was also observed in RT-PCR
      performed on these cell lines.

PMID- 9769475
TI  - Cytoskeletal reorganization induced by retinoic acid treatment of human
      endometrial adenocarcinoma (RL95-2) cells is correlated with alterations in
      protein kinase C-alpha.
AB  - We have shown previously that treatment of human endometrial adenocarcinoma (RL95
      2) cells with either 13-cis or all-trans retinoic acid results in reorganization
      of actin filaments, indicating reversion to a stationary phenotype. In the
      present study, we investigated the role of protein kinase C (PKC) in this
      process. Treatment of cells with PKC inhibitors (staurosporine,
      bisindolylmaleimide, or G?6976) resulted in morphological alterations and
      reorganization of actin filaments similar to retinoic-acid-treated cells. For
      example, RL95-2 cells treated with staurosporine flattened, exhibited cell
      surface extensions and some actin filaments. Bisindolylmaleimide-treated cells
      flattened, and actin filaments reorganized similar to retinoic-acid-treated
      cells. RL95-2 cells treated with G?6976, which inhibits only PKC, alpha, beta and
      gamma, exhibited many cell surface extensions and some actin filament
      reorganization. We then investigated whether retinoic acid affected the
      subcellular localization of PKC-alpha. In control cells, PKC-alpha was mainly
      evident as diffuse cytoplasmic immunostaining, with a small percentage of total
      PKC-alpha also evident in the plasma membrane. Retinoic acid treatment
      dramatically altered PKC-alpha localization, since a more distinct cytoplasmic
      and perinuclear staining pattern was apparent. Western blot analysis confirmed
      these results, since the amount of cytosolic PKC-alpha increased following
      retinoic acid treatment. Thus, retinoic-acid-induced endometrial differentiation
      may be associated with alterations in PKC-alpha localization and signaling.

PMID- 9769476
TI  - Regulation of cytokine-induced neutrophil chemoattractant in rat bone marrow
      derived macrophages by inflammatory mediators.
AB  - During the course of inflammation, macrophages are highly influenced by their
      local environment and changes in the cytokine milieu. Exposure of macrophages to
      various factors during different phases of the inflammatory response may have a
      strong influence on the pattern of gene expression, which a macrophage exhibits.
      We examined how these mediators affect the regulation of the expression and
      production of cytokine-induced neutrophil chemoattractant (CINC). Our study
      demonstrates that CINC can be induced in bone marrow-derived macrophages by
      lipopolysaccharide, interleukin-1 beta, tumor necrosis factor-alpha (TNFalpha),
      and interferon-gamma/TNF alpha. These mediators are factors which a macrophage
      would be expected to encounter early in an inflammatory process. In contrast,
      transforming growth factor-beta (TGFbeta), which is expressed late in the
      inflammatory process during mesenchymal cell proliferation and tissue repair, did
      not induce detectable amounts of CINC and functioned to suppress CINC production
      stimulated by early inflammatory mediators. Suppression of CINC production
      occurred whether TGF beta was added simultaneously, 12 or 24 h prior to the
      stimulus.

PMID- 9769477
TI  - Monocyte-dependent stimulation of human T cells by silicon dioxide.
AB  - Mononuclear cells were isolated by Ficoll-Hypaque density gradient centrifugation
      from randomly selected silicone breast implant recipients for testing. Restricted
      antibody to HLA-DR (28-33 kD) depleted the concanavalin A mitogenic response
      which was expected but failed to inhibit the proliferative response to silicon
      dioxide. Further testing with monoclonal antibodies to HLA-DP, -DQ, and a second 
      DR with specificity for the NS1 region of the MHC class II genome, all markedly
      inhibited proliferation of T cells despite otherwise adequate stimulation by
      concanavalin A or silicon dioxide. Monoclonal antibodies directed against B7-1
      also inhibited proliferation of T cells following stimulation with concanavalin A
      or silicon dioxide. These results confirm the T-cell response to silicon dioxide
      is monocyte-dependent and not a superantigen as has been speculated.

PMID- 9769478
TI  - Loss of heterozygosity on the short arm of chromosome 3 in cervical intra
      epithelial neoplasia without concomitant cervical carcinoma.
AB  - Losses of heterozygosity on the short arm of chromosome 3p are common in cervical
      carcinomas in the 3p13-3p21 region, and can be observed in intra-epithelial
      lesions accompanying cervical cancers. As a preliminary attempt to determine
      whether these losses can be observed in intra-epithelial cervical lesions without
      concomitant invasive carcinoma, we have used two microsatellite markers located
      at the two most frequently deleted segments of the 3p13-3p21 region. We have
      studied 36 cases of grade II and grade III cervical intra-epithelial neoplasias
      obtained by conisation biopsies and 30 cases of cervical carcinoma including 3
      micro-invasive squamous cell carcinomas. We found loss of heterozygosity or
      microsatellite instability in 6 of 16 (38%) and 9 of 23 (39%) informative cases
      of cervical carcinoma at 3p13 and 3p21, respectively. Four of 27 (15%) cases of
      cervical intra-epithelial neoplasia showed loss of heterozygosity at 3p13,
      whereas loss of heterozygosity or microsatellite instability at 3p21 was found in
      5 of 19 cases (26%). No relationship was found between 3p loss of heterozygosity
      and human papillomavirus infection. In conclusion, losses of heterozygosity at
      3p13 and 3p21 occur in premalignant lesions without concomitant invasive lesions.
      The prevalence and precise extent of these losses should be established by a more
      extensive analysis.

PMID- 9769479
TI  - The NF-kappaB and IkappaB system in injured arteries.
AB  - Activation of endothelial cells and dedifferentiation of smooth muscle cells
      (SMC) are events in the development of vascular disease. The NF-kappaB
      transcription factor family and its inhibitory proteins (IkappaB) have been
      implicated in regulating the expression of genes associated with the concomitant
      inflammatory response. To determine the role of the NF-kappaB/IkappaB system in
      vivo, the present study used the balloon catheter injury model in the rat carotid
      artery. Immunoblotting revealed that higher levels of the NF-kappaB family
      members p50, p52, p65, c-Rel, and RelB were expressed in injured arteries during
      lesion formation compared to normal vessels. Using electromobility shift assays,
      low levels of constitutively activated NF-kappaB were seen in normal carotid
      arteries and an induction occurred during times of rapid SMC proliferation.
      Furthermore, immediately after injury, the levels of the inhibitor proteins
      IkappaB alpha, IkappaB beta, and p105 were dramatically reduced. Consistent with
      the activation of NF-kappaB, vascular cell adhesion molecule-1 (VCAM-1) and
      monocyte chemotactic protein-1 (MCP-1) were induced in SMC and endothelial cells
      as early as 4 h after injury and this was accompanied by adhesion of
      monocytes/macrophages. SMC forming a pseudoendothelium in chronically denuded
      vessels continued to express high levels of VCAM-1 and MCP-1, thus perpetuating
      the inflammatory response. These findings link the activation of NF-kappaB to the
      inflammatory response and to intimal lesion formation following vascular injury.

PMID- 9769480
TI  - [HTLV-I and HTLV-II virus].
AB  - HTLV genomic and antigenic features, replication way as well as associated
      pathology are recalled herein. The epidemiologic angle and the different
      transmission ways are also related. HTLV infection diagnostic implements are
      detailed: screening and specially confirmatory tests are brought to light with
      the help of concrete examples interpreted according to the criteria defined by
      the Retrovirus Study Group of the French Blood Transfusion Society.

PMID- 9769481
TI  - [Papillomavirus infection in a woman with cervix dysplasia].

PMID- 9769483
TI  - [Procalcitonin in severe trauma].
AB  - The diagnosis of infection in systemic inflammatory syndrome response is
      difficult but essential for correct patient management. Procalcitonin is a new
      biochemical marker of infection especially for bacterial infection. Procalcitonin
      and C-reactive protein (CRP) were prospectively studied in 21 severe trauma
      patients and correlated with the trauma severity and the occurrence of infection.
      At the early post-traumatic period (admission to day 3) procalcitonin and CRP are
      correlated with the severity of trauma (early volume loading and markers of
      tissue injury) as did typically acute inflammatory proteins. At the late post
      traumatic period (day 7) while CRP concentrations remain elevated in all
      patients, procalcitonin concentrations are only raised in septic patients even if
      inflammation's clinical signs persist.

PMID- 9769484
TI  - [Apolipoprotein B and LDL cholesterol: which parameter(s) should be included in
      the assessment of cardiovascular risk?].
AB  - High level of plasma apo B lipoproteins is a risk factor for coronary artery
      disease. However, which lipid parameters should be routinely assayed is a
      question still in debate. For this purpose, the authors have studied issues since
      1992 comparing predictive and discriminative values of LDL-cholesterol and apo B
      in order to assess coronary artery disease. Indeed the respective advantages of
      these markers were still being discussed after an exhaustive review had been
      completed in 1992. Despite the number of the debates, none of the few studies
      about this topic rise any decisive arguments. In conclusion it is proposed that a
      true comparison of the predictive values of LDL-cholesterol and apo B should be
      carried out before making definitive recommendations concerning their clinical
      utility.

PMID- 9769485
TI  - [Technical test of the AlaSat system].

PMID- 9769488
TI  - [Property of antibody avidity in the detection of toxoplasmosis seroconversion].

PMID- 9769492
TI  - [Waste disposal risk in a biochemistry laboratory].

PMID- 9769494
TI  - [1972-1997: an anniversary...for children in good health].

PMID- 9769493
TI  - [A case of congenital nephrotic syndrome].

PMID- 9769495
TI  - [Nosocomial outbreaks: advantages and limitations of environmental cultures].

PMID- 9769499
TI  - [Accreditation of French medical laboratories].

PMID- 9769496
TI  - [Analytic evaluation of Immage for ten proteins].

PMID- 9769500
TI  - [Metastatic cancer in an 82 year old woman: bone marrow infiltration and
      disseminated intravascular coagulation].

PMID- 9769503
TI  - [Glutamine and the liver cell: metabolism, properties and the concept of
      metabolic regulation by cell swelling].
AB  - Glutamine is transported into the hepatocyte in a sodium-dependent manner. A
      consequence of the sodium-dependent entry of glutamine is an osmotic swelling of
      the cell. In the past, glutamine has been given a number of anabolic properties
      such as the stimulation of both glycogen and lipid synthesis from glucose. The
      mechanism through which glutamine activates key enzymes in these metabolic
      pathways involves the glutamine-induced cell swelling. Moreover, glutamine
      regulates gene expression of the beta-actin gene at a transcriptional level as
      well as that of the phosphoenolpyruvate carboxykinase gene by stabilizing its
      mRNA. Regulation of gene expression by glutamine also involves the cell swelling
      phenomena. Cell swelling is now regarded as a novel regulatory element of hepatic
      metabolism.

PMID- 9769507
TI  - [Erythrocyte, plasma and substitute hemoglobins facing physiological oxidizing
      and reducing agents].
AB  - Oxidation of hemoglobin is constant and normal in red blood cells and in all
      biological media. The knowledge of the mechanisms which manage oxidation state is
      perhaps sufficient to treat acquired and some hereditary methemoglobinemia. But
      in case of transfusional treatment with hemoglobin based oxygen carrier (HBOC),
      some preclinical investigations on the oxidation of these products in vivo in
      plasma showed that our knowledge was not sufficient to understand and control all
      oxidations which could occur. This review analyses the literature on the
      different mechanisms in red blood cells and plasma by which hemoglobin
      autooxidizes and by which endogenous oxidizing agents or their precursors (nitric
      oxide, peroxynitrite, superoxide, hydrogen peroxide) could oxidize it. It shows
      the production of different radical or non-radical oxygen species during
      hemoglobin autooxidation and oxidation processes and the different physiological
      or accessory mechanisms that could prevent or reduce the various oxidizing states
      of hemoglobin (HbFe3+, HbFe4+) in blood. Plasma contains a few anti-oxidizing or
      reducing systems but it profits by antioxidizing and reducing activity from red
      blood cells. In blood, oxidation state of hemoglobin results from very complex
      phenomena and if the body struggles against methemoglobin formation to maintain
      oxygen transport, the oxidation of hemoglobin is sometimes useful to protect
      tissues against various and numerous endogenous radical or non-radical oxidizing
      agents. In blood, a balance between all these oxidizing and reducing mechanisms
      makes it possible to regulate circulating methemoglobin rate.

PMID- 9769506
TI  - [Determination of procalcitonin in the diagnosis of maternal-fetal infections].

PMID- 9769509
TI  - [Definitions of accreditation].

PMID- 9769510
TI  - [Confirmation of collective histamine poisoning origin by rapid high pressure
      liquid chromatography].

PMID- 9769514
TI  - [Setting up a quality assurance system for the management of blood glucose
      monitoring in hospital units].

PMID- 9769516
TI  - [Role of biology in the follow up of viral hepatitis].
AB  - Biological tests are important for the diagnosis and the follow-up of viral
      chronic hepatitis. The viral hepatitis C is by far the most frequent. The
      etiologic diagnosis is based on serological or immunological tests which have
      good sensitivity and specificity, and may be completed by molecular biological
      methods. In contrast, the tests for the evaluation of the activity (necrosis and
      inflammation) and of the fibrosis are less informative than the histological
      study. The diagnosis and prognosis interpretation of the aminotransferases are
      well known, but other tests as alpha glutathione S-transferase or orosomucoid are
      also proposed for evaluation of the activity. Some parameters as PIIINP or
      hyaluronic acid may be useful in the diagnosis and follow-up of fibrogenesis,
      fibrosis and cirrhosis but some new molecules, as the metalloproteinases and
      their inhibitors, are presenting interesting future prospects. Biological tests
      also contribute to the diagnosis of an associated extra-hepatic pathology and of
      a possible hepatocellular carcinoma occurring on the cirrhotic liver.

PMID- 9769518
TI  - The challenge of hepatitis management in Australian general practice.

PMID- 9769517
TI  - [Semiologic value of LDL cholesterol and apolipoprotein B in risk of
      atherosclerosis].

PMID- 9769519
TI  - Caring for the Chinese patient in general practice.

PMID- 9769520
TI  - Should consumers be involved with CME?

PMID- 9769521
TI  - Atlas rotation following a blow to the neck.

PMID- 9769523
TI  - Reform or doctor bashing?

PMID- 9769522
TI  - A health union.

PMID- 9769524
TI  - Update on the management of hepatitis C.
AB  - BACKGROUND: Hepatitis C is common and most patients with hepatitis C will develop
      chronic hepatitis. A significant proportion of patients develop cirrhosis and
      there is a definite but unquantified risk of hepatocellular carcinoma. OBJECTIVE:
      This article examines the latest treatments available for hepatitis C.
      DISCUSSION: Interferon alfa is the only currently proven treatment but recent
      trials suggest that combination therapy with Ribavirin improves sustained long
      term response rate. Patients should be counselled regarding the mode of
      transmission of the virus. Patients with cirrhosis should be screened for
      hepatocellular carcinoma and liver transplantation should be considered for
      patients with decompensated disease.

PMID- 9769525
TI  - Aspects of care for the hepatitis C positive patient.
AB  - BACKGROUND: With almost 200,000 infected Australians, hepatitis C is Australia's
      commonest life threatening chronic infection. OBJECTIVE: Over 90% of the 11,000
      new infections in Australia each year are associated with injecting drug use.
      Australia does not have a national plan for achieving control of hepatitis C.
      Treatment at present is expensive, less effective than many other conditions and
      associated with considerable side effects. DISCUSSION: Most people with chronic
      hepatitis C infection have a normal life expectancy with good quality of life.
      The role of general practitioners in prevention and treatment is increasing.

PMID- 9769526
TI  - Chronic hepatitis C infection. A disease ideally suited to management in the
      primary care setting.
AB  - BACKGROUND: The currently sub-optional efficacy of therapy for chronic hepatitis
      C infection makes other management modalities a priority. OBJECTIVE: To address
      issues in overall management of hepatitis C infection through case studies.
      DISCUSSION: Management of hepatitis C infection should cover discussion of
      hepatitis C transmission, natural history (prognosis) and therapy. A polymerase
      chain reaction (PCR) for detection of hepatitis C RNA should be ordered in those
      patients with persistently normal liver function tests to determine the presence
      or absence of chronic infection. Other measures include assessment and
      counselling in relation to alcohol intake, and vaccination against both hepatitis
      A and hepatitis B. In patients with abnormal liver function tests a liver biopsy
      should be considered in order to determine the stage of disease, thus enabling
      targeting of therapy to those at highest risk of progression to advanced liver
      disease.

PMID- 9769527
TI  - Hepatitis C. Issues for women and their partners.
AB  - BACKGROUND: A large proportion of injecting drug users in Australia have been
      found to have hepatitis C virus (HCV). Many of these are women who as a result of
      the disease have specific concerns related to risk of transmission to spouses and
      children and questions regarding what contraception they can use. OBJECTIVE: This
      paper reviews the literature to examine the relationship between hepatitis C and:
      limitations on contraceptive use; whether sexual transmission can occur between
      couples; whether transmission occurs within households; rates of vertical
      transmission; whether transmission can occur through breastfeeding. DISCUSSION:
      While the prevalence of hepatitis C is low in women (except where a known history
      of injecting drug use exists) a small risk of sexual and vertical transmission
      exists when viral loads are high (such as in acute phases of the disease) or when
      the infected person is immunocompromised. New technologies such as polymerase
      chain reaction (PCR) testing may allow better advice to be given about the
      transmissibility of disease. Hormonal contraception may worsen liver function and
      general practitioners need to take this into account when discussing
      contraceptive options with their patient.

PMID- 9769528
TI  - Caring for the hepatitis C patient. A step by step guide. National Hepatitis C
      Education Program for GPs, Gastroenterology Society of Australia (GESA)
      Hepatology Section.

PMID- 9769529
TI  - How to obtain funding for your project.
AB  - Project development is an exacting and time consuming task. Grant applicants may
      expend inordinate amounts of time searching the literature on their topic area,
      consulting with experts in the field and others who have run similar research or
      projects, eliciting and incorporating the views of major stakeholders and
      developing a method to answer the research question. While those who are
      successful in attracting funding experience the elation that accompanies
      achievement, those whose applications are rejected may experience profound
      disappointment. The aim of this paper is to maximise the potential for
      researchers to celebrate their success by suggesting a number of strategies for
      avoiding the pitfalls of application development. Potential sources of funding
      are also discussed.

PMID- 9769530
TI  - General practitioner involvement in hospital in the home. The hospital's view.
AB  - INTRODUCTION: Programs involving hospitals and general practitioners (GPs) have
      become more commonplace, with a greater emphasis on integration of health
      services emerging over the last generation. Hospital in the home (HIH) refers to
      the delivery of acute hospital services such as intravenous therapy,
      anticoagulation and wound care to patients in their own homes. This study sought
      to determine the extent to which HIH units had involved urban GPs, issues related
      to GP involvement, and the likely future of such involvement. METHOD: Telephone
      administered structured survey to all urban HIH coordinators/directors in
      Melbourne, Australia. RESULTS: All 14 identified HIH coordinators were
      interviewed. Five units reported a direct role for GPs, six reported no role and
      three reported a limited role in managing intercurrent illnesses. Coordinators
      felt that variability of GP response and skills, GP availability and patient
      control were significant issues. An increase in future GP involvement was
      uncertain and conditional. DISCUSSION: One-third of urban hospitals surveyed have
      involved GPs in their programs. However, issues such as variability in skills,
      enthusiasm and availability threaten expansion of such involvement. This calls
      for a review in the way GPs are involved in hospital programs, and for better
      relationships with hospital nursing staff. Limiting the number of involved GPs in
      any hospital-GP program may offer advantages to both groups. Despite the movement
      of hospital work into the community, GP involvement in such work is not
      guaranteed.

PMID- 9769531
TI  - 'I just want some Valium, Doc'.
AB  - BACKGROUND: Consultations with drug seeking patients are common and often
      stressful. Conscientious general practitioners who prefer not to prescribe
      addictive drugs can experience awkward or unpleasant confrontations with
      patients. OBJECTIVE: This article describes a way of dealing with such
      consultations in order to minimise the difficulties, while maximising the
      opportunity for good patient care. Some of the common concerns about not
      prescribing for drug seekers are discussed. DISCUSSION: As with all situations in
      general practice, there is no single 'right' approach, but what follows may add
      to our armoury of available responses.

PMID- 9769532
TI  - Musculoskeletal chest pain.

PMID- 9769533
TI  - Radiology quiz. Ultrasound investigation of pelvic pain.

PMID- 9769534
TI  - Golfer's heel. Part 2.

PMID- 9769535
TI  - The worm that turned.

PMID- 9769536
TI  - Patient education. Hepatitis C. What is it and how did I get it?

PMID- 9769537
TI  - Practice tip. Hepatitis C counselling. An overview.

PMID- 9769538
TI  - Pregnancy in the workplace.

PMID- 9769539
TI  - Bad representation in the media.

PMID- 9769540
TI  - Handling of a sensitive issue.

PMID- 9769541
TI  - The erosive potential of alcopops.

PMID- 9769542
TI  - Banning of powdered latex gloves.

PMID- 9769543
TI  - Harmony between primary care providers.

PMID- 9769544
TI  - Sensationalism or tolerance?

PMID- 9769545
TI  - Nothing but the truth.

PMID- 9769546
TI  - The hidden dangers of refrigerated confectionary.

PMID- 9769547
TI  - Manpower in general practice.

PMID- 9769548
TI  - Assistance in Georgia.

PMID- 9769549
TI  - E-mail: what is e-mail?
AB  - This third part of the series explains what e-mail is and why it is the most
      widely used service on the internet. The principles behind sending and receiving
      e-mail messages are described. Also the various uses of e-mail are discussed.

PMID- 9769550
TI  - An update on dental imaging.
AB  - This paper reviews recent advances and current trends in dental radiology.
      Developments in the design of dental x-ray equipment which improve both radiation
      hygiene and image quality are described. Also discussed are new features which
      broaden the scope of intra-oral and panoramic radiological diagnosis in the
      general dental practice setting. The article concludes with the main
      recommendations from the latest guidelines on quality standards for radiography,
      selection criteria and quality assurance in general practice.

PMID- 9769551
TI  - The EU manual of dental practice--a guide for dentists planning to practice
      abroad.
AB  - How does a dentist go about moving practice to another EU country? This article
      describes a new publication which aims to explain the dental practice
      arrangements in a number of European countries and clear up the EU red tape.

PMID- 9769555
TI  - Orthodontic auxiliaries--a pilot project.
AB  - AIM: To undertake a pilot study to determine a possible training programme for
      orthodontic auxiliaries. DESIGN AND SETTING: Trainee hygienists who had been
      accepted onto a 2-year programme were asked to attend the Bristol Dental School
      well before their course was due to begin in order to participate in a pilot
      orthodontic assistant auxiliary training programme. METHODS: A modular course of
      one month's duration was constructed based on the programme at the University of
      British Columbia. This aimed to teach skills such as impression taking, bond
      placement, debracketing, band cementation as well as core knowledge relevant to
      these procedures. RESULTS: At the end of the course all participants were judged
      to be performing the tasks they had been taught competently and safely.
      CONCLUSION: UK dental nurses can be trained to fill the role of an orthodontic
      auxiliary. It would appear that an introductory clinical skills course of one
      week followed by an orthodontic skills training of three weeks is sufficient for
      a qualified dental nurse of above average abilities such as typifies those who
      are currently applying for places on UK dental hygiene courses. It is estimated
      that a further period of nine months supervised training will be necessary for
      those who have successfully completed such a training to develop clinically
      useful speeds when delivering these skills.

PMID- 9769556
TI  - Attitudes of Chinese people toward obtaining dental care in the UK.
AB  - OBJECTIVE: To explore the attitudes of Chinese people regarding dentists and
      toward obtaining dental care in the UK. INTRODUCTION: Injudicious use of general
      health services has been reported among Chinese people in the UK. In relation to
      oral healthcare, the extent to which cultural beliefs and values affect use
      remains uncertain. SETTING: Chinese communities in the north east of England.
      SUBJECTS AND METHODS: A quota sample of 156 Chinese people was recruited in 1996.
      50 elderly people, 56 adults, 50 teenagers were interviewed by 5 trained and
      standardised multilingual Chinese interviewers using a validated structured
      questionnaire. RESULTS: Access varied substantially according to age, with the
      younger generations more likely to obtain dental care without difficulty.
      Overall, the sample perceived that dentists possessed adequate technical
      competence, but their patient management skills lacked sensitivity. Older Chinese
      people placed less trust in dentists. Many elderly people reported problems in
      finding a UK dentist and would have preferred one of Chinese origin. Potential
      problems in follow-up prosthetic dental care were also apparent among this age
      group. Cost, communication problems, anxiety and cultural beliefs were identified
      as major barriers to dental care. CONCLUSIONS: There is a clear need to raise
      cultural awareness among dental professionals as well as to help Chinese people's
      positive attitudes toward dentists and dental care.

PMID- 9769557
TI  - Clinical quality assurance indicators for oral status and treatment of a group of
      older adults.
AB  - OBJECTIVE: To record and comment on the oral status and treatment provision over
      a 3-year period for a group of 150 patients aged between 50 and 64 with special
      reference to the WHO (ORATEL) quality assurance indicators. DESIGN: 150 patients
      in the defined age group who were attending a general dental practitioner for a
      routine examination were sampled over a 3-month period. The oral status was
      recorded by the GDP at the time of attendance and a retrospective analysis of
      treatment provided over three years was carried out by reference to the patient
      case notes. RESULTS: An analysis of the data relating to oral health status and
      previous treatment provision suggested that some indicators were easy to
      accurately record while others lacked clear diagnostic criteria. There were also
      some inconsistencies in format. There was a lack of coverage in a few important
      areas and some additional indicators were suggested. CONCLUSIONS: The ORATEL
      indicators form a useful core dataset for GDPs to use to measure oral health
      change within the patient base of their practices. The recording and analysis of
      quality assurance indicators by the GDP could make a significant contribution to
      the monitoring of the oral health change of patients in general dental practice.

PMID- 9769558
TI  - No change at the top.

PMID- 9769559
TI  - Ultrasound and alendronate: new tools for osteoporosis screening and treatment.
AB  - Office-based physicians can now use ultrasonography of the heel to screen for
      osteoporosis and estimate the risk of fractures. In treating osteoporosis,
      alendronate has been shown to increase bone mineral density and to decrease the
      incidence of fractures.

PMID- 9769561
TI  - Upper gastrointestinal bleeding in a 41-year-old woman.

PMID- 9769560
TI  - Enthusiasm for ultrasound for osteoporosis screening is premature.

PMID- 9769562
TI  - Hepatitis C update: implications of the blood transfusion "lookback".
AB  - Over the next several years, physicians will be called upon to notify past blood
      transfusion recipients of blood that may have been contaminated with hepatitis C
      virus (HCV). This article reviews the screening, care, and follow-up of persons
      at risk for hepatitis C virus infection from all sources.

PMID- 9769564
TI  - Our new understanding of heart failure: the role of beta-blockers in treatment.
AB  - Beta-blockers, long considered contraindicated in heart failure, improve left
      ventricular function in this disease by improving the biology of cardiac
      myocytes. Whether they improve survival remains to be determined.

PMID- 9769563
TI  - Lipid formulations of amphotericin B.
AB  - Amphotericin B has long been the mainstay in the treatment of systemic fungal
      infections, but its nephrotoxicity limits the dosage that can be used. New lipid
      based forms may allow higher dosing with less nephrotoxicity. Unfortunately,
      these new forms are substantially more expensive, and data from randomized
      clinical trials of their relative efficacy are as yet limited.

PMID- 9769565
TI  - Rheumatologic manifestations of HIV-1 and HTLV-1 infections.
AB  - HIV infection is the new "great mimic." Although its more common signs and
      symptoms are well known, HIV infection sometimes presents with rheumatologic
      manifestations, as does human T-cell lymphotrophic virus type I (HTLV-I), the
      causative agent of adult T-cell leukemia. This review briefly describes these
      manifestations and presents a logical clinical approach to their diagnosis and
      treatment.

PMID- 9769566
TI  - Agitated dementia.

PMID- 9769567
TI  - Agitated dementia.

PMID- 9769568
TI  - Politics & patients' rights.

PMID- 9769569
TI  - Should government intervene to protect nonprofits?
AB  - The emergence of investor-owned firms as major actors in U.S. health care
      financing and delivery has led to calls for federal and state intervention to
      protect nonprofits and to stem the for-profit sector's growth. High-profile
      scandals involving some of these firms have lent urgency to such proposals. This
      paper considers the case for government intervention to protect the nonprofit
      health sector. The controversy over the comparative merits of nonprofits and for
      profits is reformed as a debate over the potential and limits of government
      action, and the case for a general presumption favoring protection for nonprofits
      is found to be unpersuasive.

PMID- 9769570
TI  - A broader vision for managed care, Part 2: A typology of community benefits.
AB  - Applying a "community benefit" standard to managed care is difficult because
      prevailing definitions of community benefit have been drawn largely from the
      hospital industry, which has different operating practices and capabilities than
      managed care plans do. To formulate a more comprehensive and appropriate typology
      for managed care, we describe four different conceptual perspectives on community
      benefit and identify actual plan practices that match each perspective. We
      propose a "balanced model" for encouraging community benefit through public and
      private policies.

PMID- 9769571
TI  - The ethics of accountability in managed care reform.
AB  - Two notions of accountability embodied in proposals to reform managed care have
      different ethical implications. Market accountability requires plans to inform
      purchasers and consumers about performance and options, in theory legitimizing
      limits to care through consumer choice. Recognizing the limits of consumer
      choice, accountability for reasonableness requires that the rationales for limits
      to services be public and be based on reasons or rules that "fair-minded" people
      can agree are relevant to pursuing appropriate patient care under necessary
      resource constraints. Accountability for reasonableness educates clinicians and
      patients about the need for limits and empowers a more focused public
      deliberation in which ultimate authority for limiting care rests with democratic
      processes.

PMID- 9769572
TI  - The Federal Trade Commission in action: the FTC's Robert F. Leibenluft. Interview
      by John K. Inglehart.

PMID- 9769574
TI  - How are health care organizations using clinical guidelines?
AB  - Although policymakers are increasingly interested in how integrated delivery
      systems and managed care plans implement clinical guidelines and improve
      performance and quality of care, few data have been compiled about how these
      organizations are undertaking change. Interviews with officials in organizations
      that are engaged in improving practice across the country documented that there
      is a profound transformation under way with substantial similarity in the
      approaches being used by otherwise very different plans. Better evaluation of the
      effectiveness and cost-effectiveness of these approaches could provide a more
      solid foundation for policies to improve quality of care.

PMID- 9769573
TI  - Outcomes and effectiveness research in the private sector.
AB  - Private-sector health care organizations increasingly tout the use of outcomes
      and effectiveness research in activities ranging from pharmaceutical research to
      insurance coverage determinations. The rapid development of this research raises
      important questions about the role of the Agency for Health Care Policy and
      Research (AHCPR) as the producer, funder, and champion of outcomes and
      effectiveness research. To address this issue, we reviewed the activities of
      pharmaceutical companies, insurers, managed care organizations, health
      information technology companies, and other private-sector actors in outcomes and
      effectiveness research. We found that it is being used in a focused way to
      promote business goals and other organizational objectives, particularly in the
      pharmaceutical, insurance, and managed care industries. We also found significant
      gaps in its application to important public health issues and virtually no
      overlap with prior federal activities in this area.

PMID- 9769575
TI  - 'More a link than a division': how Canada has learned from U.S. mental health
      policy.
AB  - The Canadian health care system has been frequently discussed but firmly rejected
      as a model for guiding the transformation of American medicine. In mental health
      care, however, one can find a growing convergence between the two systems. This
      convergence is largely coming about as a result of Canadian borrowing from
      American programs and strategies. In this paper we provide examples of planning
      service, and policy elements in U.S. mental health care that Canadians have drawn
      upon. We analyze this phenomenon in terms of cross-national policy learning,
      identifying the factors and forces that facilitate this trend for Canada while
      impeding it for the United States.

PMID- 9769576
TI  - The next ten years of health spending: what does the future hold? The Health
      Expenditures Projection Team.

PMID- 9769577
TI  - Tracking health care costs: what's new in 1998?

PMID- 9769578
TI  - Spending for mental health and substance abuse treatment, 1996.

PMID- 9769579
TI  - The new generation of nurse practitioners: is more enough?

PMID- 9769580
TI  - Promoting choice: lessons from managed Medicaid.
AB  - Drawing on the education, enrollment, and assignment experiences of seven states
      with mandatory Medicaid managed care programs, this paper finds that the vast
      majority of enrollees will choose their own health plan if the system is
      explicitly designed with this in mind (as in Minnesota and Oregon). These
      experiences provide lessons on ways to 1) align program design with state
      priorities; (2) increase the level of choice (by coordinating enrollment and
      eligibility processes, broad-based educational strategies, and personalized
      attention); (3) improve the quality of choice; and (4) design state contracting
      processes to support choice and continuity of care.

PMID- 9769581
TI  - When warnings are not enough: primary prevention through drug use review.

PMID- 9769582
TI  - Does dissatisfaction with health plans stem from having no choices?
AB  - Data from a 1997 nationwide telephone survey are used to assess the relationship
      between choice and public opinion about managed care. We found that only a
      minority of the working-age population effectively control what health plan they
      get. Persons without choice were markedly more dissatisfied with their health
      plan, especially when enrolled in managed care. In multivariate analysis, how
      respondents rated their health plan depended as much on whether they lacked
      choice as on whether they were enrolled in managed care. Persons without choice
      also had more negative opinions about managed care in general. The results
      suggest that the managed care "backlash" may persist so long as consumers have
      little control over health insurance decisions.

PMID- 9769583
TI  - Managed care and technology diffusion: the case of MRI.
AB  - A growing body of evidence suggests that managed care can reduce overall health
      care costs but provides little insight into how this could happen. One
      possibility is that managed care influences the adoption of new medical
      technologies. In examining the relationship between health maintenance
      organization (HMO) activity and market-level availability and use of magnetic
      resonance imaging (MRI), we find that high HMO market share is associated with
      low levels of MRI availability and use. This suggests that managed care may be
      able to reduce health care costs by influencing the adoption and use of new
      medical equipment and technologies.

PMID- 9769584
TI  - Effects of maternity-stay legislation on 'drive-through deliveries'.
AB  - We evaluate the change in length-of-stay and charges for vaginal and cesarean
      deliveries before and after the implementation of a law establishing a minimum
      maternity stay in Maryland. Using discharge abstract data collected by the
      Maryland Health Services Cost Review Commission, we find that after the law was
      enacted, Maryland's average length-of-stay and average charges for both types of
      deliveries increased, but the increase in charges was less than the cost of an
      average hospital day. Multivariate analysis shows that the implementation of the
      law reduced the sources of variation among mothers' length-of-stay and hospital
      charges. Overall, we estimate that the law cost payers an additional $5.5 million
      for maternity stays.

PMID- 9769585
TI  - Health policy grant making by foundations in the 1990s.

PMID- 9769586
TI  - Health grantmakers and public policy.

PMID- 9769587
TI  - Good news about difficult decisions: the Canadian approach to hospital cost
      control.

PMID- 9769588
TI  - Community benefit via social coercion?

PMID- 9769589
TI  - Dangers of inpatient rehabilitation industry consolidation.

PMID- 9769590
TI  - Health services research and state policy in action.

PMID- 9769591
TI  - Certified nurse-midwife supply.

PMID- 9769592
TI  - Evaluating hospital mergers.

PMID- 9769593
TI  - Immunobead and density gradient purification of Paget cells: in vitro studies of
      proliferation.
AB  - Previous studies using primary monolayer cultures of epithelial cells from the
      involved epidermis of patients with mammary and extramamary Paget's disease
      investigated whether Paget cells proliferate as other malignant cells do.
      Although epithelial monolayers from the involved skin were maintained for
      approximately 45 days, no permanent cell lines were established. The proportion
      of carcinoembryonic antigen (CEA)-positive cells did not increase in the long
      term cultures. Herein, we report studies of whether there is a real reduction of
      Paget cell numbers or if this is merely a decrease in the expression of CEA by
      the cells. Furthermore, we investigated whether Paget cells survive longer when
      cultured free from any potential inhibitory keratinocytes or other epidermal
      cells. Skin samples were obtained from one patient with mammary Paget's disease
      and three with extramammary Paget's disease; epidermal cells were cultured in
      vitro. An enrichment of Paget cells was carried out from the cultured epidermal
      cells by combining an antiepithelial membrane antigen monoclonal antibody,
      binding to immunobeads, and density gradient centrifugation in Nycodenz. The
      separated cells were re-cultured in Keratinocyte-SFM serum-free media. The
      proportion of CEA-positive cells did not increase in the culture, and the
      purified cells did not show any increase in survival times compared to the non
      purified cultured cells. These results suggest that the decrease of CEA-positive
      cells noted during culture results from a decline in expression of CEA in the
      Paget cells. Paget cells in the involved epidermis do not proliferate
      significantly and thus differ from many other malignant cells.

PMID- 9769594
TI  - Linear IgA bullous dermatosis with circulating IgG autoantibodies to the 230 kD
      epidermal antigen.
AB  - The patient was a 54-year-old woman with wide-spread bullous lesions on her trunk
      and oral mucosa. Histologic examination revealed a subepidermal blister with
      infiltration of neutrophils and eosinophils. Direct immunofluorescence showed an
      exclusively IgA deposition at the basement membrane zone (BMZ). Indirect
      immunofluorescence showed that the blister fluid, but not the serum, contained
      IgG antibodies against the BMZ antigen on the epidermal side of salt-split skin.
      Using immunoblot analysis with normal human epidermal extracts, both serum and
      blister fluid reacted with the 230 kD epidermal antigen. Using colloidal gold and
      direct immunoelectron microscopy, IgA deposition was detected in the lamina
      lucida. Clinically, the skin lesions responded well to dapsone. We diagnosed this
      case as linear IgA bullous dermatosis (LABD) with IgG class circulating
      autoantibodies against the epidermal 230 kD antigen. These antibodies were
      considered to be secondary to the damage to the epidermal basal keratinocyte in
      this case.

PMID- 9769595
TI  - Hormonal milieu in the maintenance of melasma in fertile women.
AB  - Melasma is a specific type of facial hyperpigmentation seen in women taking oral
      contraceptives, in non-pregnant women who have not used oral contraceptives, and
      in some pregnant women during the progression of gestation, but rarely in men.
      Circulating LH, FSH, PRL, and E2-17 beta on day 5, 7, 9, and 11 of the menstrual
      cycle and progesterone (P) on day 17, 19, and 21 were measured in thirty-six
      ovulating women with melasma (study group) age 25-35 years and twelve healthy
      controls (control group). Twenty-seven subjects in the study group had normal
      pregnancies; 9 others were married or single and had no history of contraceptive
      pill use. Higher levels of FSH on day 7 (p < 0.05); E2-17 beta on 5, 7, 9 (p <
      0.05) and LH on day 9 (p < 0.002) were observed in the study group than in the
      control group. There were no significant differences between the LH/FSH ratio in
      the two groups. Serum PRL was lower on day 9 in the study group (p < 0.05) than
      in the control group. Serum P was similar in the patients and the controls. These
      findings indicate a possible role of high E2-17 beta in the maintenance of
      melasma.

PMID- 9769596
TI  - The levels of plasma interleukin-2 and soluble interleukin-2R in Behcet's
      disease: a marker of disease activity.
AB  - It is well known that patients with Behcet's disease (BD) have an activated
      immune system, probably mediated by soluble factors in the circulation. The
      purpose of our study was to examine the roles of plasma interleukin-2 (IL-2) and
      soluble interleukin-2 receptor (sIL-2R) in the pathogenesis of BD. Thirty-two
      patients with BD diagnosed according to the Criteria of the International Study
      Group for Behcet's Disease and 20 age-matched healthy persons were included in
      the study. The plasma levels of cytokines were measured by ELISA. Plasma levels
      of IL-2 and sIL-2R were increased in BD over controls, but the differences were
      not statistically significant. sIL-2R levels in patients with active disease were
      significantly higher than in either patients with inactive disease (p < 0.001) or
      the control group (p < 0.05). Our results suggest that the level of sIL-2R in BD
      seems to be related to disease activity.

PMID- 9769597
TI  - Clinical phenotype of Bart's syndrome seen in a family with dominant dystrophic
      epidermolysis bullosa.
AB  - BACKGROUND: Bart's syndrome is one type of dominant dystrophic epidermolysis
      bullosa (EB). It is known that, in some familial cases of dominant dystrophic EB,
      the symptoms differ depending on the individual. We observed the way Bart's
      syndrome affected four generations in the same family. The proband was a newborn
      boy who showed congenital localized absence of skin (CLAS) and bullae on the
      anterior aspects of both legs. Histologically, the bullae were located
      subepidermally. The CLAS and bullae disappeared within 4 months after birth,
      leaving scars. His father retained scarring and scaling from the knees down along
      the anterior aspect of the legs, and the nails of the toes were either lacking or
      deformed. His paternal grandmother and great-grandmother also presented deformed
      nails of the toes, although they had not had CLAS or bullae on the legs at birth.
      The individuals in this family thus showed some heterogeneity depending on the
      sex: blistering and CLAS were seen on the legs soon after birth in the male
      family members, but the female members did not share this pattern of symptoms,
      suggesting that the expression of symptoms may differ depending on the sex of the
      affected individual.

PMID- 9769598
TI  - A case of infantile digital fibromatosis with spontaneous regression.
AB  - We reported a fourteen-month-old boy with infantile digital fibromatosis. At the
      age of seven months, a nodule appeared on the back of the left third toe, and
      developed into a slight red tumor divided into five hemispherical nodules.
      Histopathologically, spindle-shaped tumor cells with an eosinophilic inclusion
      body in the cytoplasm were seen in the dermis. Electron microscopy showed a dense
      body in the cytoplasm of the tumor cells. One year and two months after the first
      visit, the tumor regressed without any aggressive treatment. Japanese cases of
      infantile digital fibromatosis were reviewed. The literature review and our case
      suggest that the tumor should be observed without any aggressive treatment unless
      it causes mobile dysfunction of the affected finger or toe.

PMID- 9769599
TI  - Disseminated cutaneous rhinosporidiosis.
AB  - Two cases of longstanding rhinosporidiosis developed widespread asymptomatic
      nodular skin lesions. Cutaneous examination showed multiple, discrete, sessile
      and pedunculated, smooth and warty, friable nodular lesions of variable sizes and
      shapes. Histopathology of representative skin lesions showed hyperplastic
      epidermis with sporangia containing spores in the upper dermis diagnostic of
      rhinosporidiosis. Epidemiological data about rhinosporidiosis at Jawaharlal
      Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry,
      India, is presented. Possible modes of dissemination to the skin and differential
      diagnosis are discussed in relation to this rare manifestation of
      rhinosporidiosis.

PMID- 9769600
TI  - Toxic epidermal necrolysis with severe gastrointestinal mucosal cell death: a
      patient who excreted long tubes of dead intestinal epithelium.
AB  - TEN is a severe inflammatory disease which is characterized by generalized
      epithelial destruction. The epidermis is the most common target of TEN, however,
      any epithelium can be involved. We report a toxic epidermal necrolysis (TEN)
      patient who excreted long tubes of dead intestinal epithelium. Epidermal
      keratinocytes and intestinal epithelium were found to undergo extensive apoptosis
      by TUNEL method. Drugs were speculated as the causative agents for this case, the
      causative drug has not been identified. In contrast to marked improvement of
      cutaneous manifestation and hepatic function by methyl prednisolone pulse
      therapy, the gastrointestinal symptoms did not respond to therapies, and the
      patient died by heart failure. Present case suggested a pathogenetic mechanism
      targeting antigens commonly expressed on the gastrointestinal epithelium and
      epidermis.

PMID- 9769601
TI  - Dermatomyositis and nasopharyngeal carcinoma.
AB  - A nasopharyngeal carcinoma was diagnosed in a 37-year-old man with a two year
      history of dermatomyositis. The physical and laboratory examinations excluded
      further medical problems. To our knowledge, this is the first case of
      dermatomyositis associated with nasopharyngeal carcinoma in a white Israeli
      Jewish patient.

PMID- 9769602
TI  - The discrepancy in hardness between clinical and histopathological findings in
      localized scleroderma treated with PUVA.
AB  - Topical PUVA therapy was applied to a patient with localized scleroderma. Her
      localized scleroderma responded very well to the topical PUVA therapy, i.e., her
      sclerotic skin softened to normal skin texture. However, despite this dramatic
      clinical change the histopathological findings did not change at all and were
      still "hard".

PMID- 9769603
TI  - Malignant chondroid syringoma.
AB  - Malignant chondroid syringoma (MCS) is a rare tumor, of the sweat gland; only a
      few hundred such cases are reported in literature. A female presented with a
      subcutaneous swelling on the scalp with repeated recurrence and positive regional
      lymph nodes. Adequate planning for the treatment of this case was possible as
      preoperative diagnosis of MCS was documented by fine needle aspiration cytology
      (FNAC). The case was successfully managed with a multimodal approach, which
      included radical surgery and subsequent radiotherapy. The patient is symptom free
      after 25 months. The possibility of this type tumor should be entertained when
      multiple recurrences occur following adequate excision. FNAC has a definitive
      role in planning rational therapy.

PMID- 9769604
TI  - Pemphigus vulgaris associated with transient acanthosis nigricans like lesion.
AB  - A patient with pemphigus vulgaris was treated with predonisolone and cyclosporin.
      At the sites of healing erosions, hyperkeratotic, hyperpigmented plaques
      developed; they were clinically and histologically similar to acanthosis
      nigricans. These lesions regressed after a few months. This case and others
      described in the literature suggest that such dermatoses might be caused by
      immunologically as well as mechanically mediated epidermal injury.

PMID- 9769605
TI  - Subcutaneous tissue involvement of CD30-positive large cell lymphoma.
AB  - There are several types of T-cell lymphoma presenting with subcutaneous tissue
      involvement showing different clinical features and prognoses. The entity of
      subcutaneous involvement of T-cell lymphoma should be differentiated. We report a
      case of CD30-positive large cell lymphoma which initially presented with
      subcutaneous tissue involvement only, but progressed to systemic dissemination.

PMID- 9769606
TI  - Are atopy and palm-sole hyperlinearity clinical tools in the differential
      diagnosis between ichthyosis vulgaris and X-linked ichthyosis?

PMID- 9769607
TI  - Environmental estrogens increase expression of SS-A/Ro autoantigen in normal
      human epidermal keratinocytes.

PMID- 9769608
TI  - The index of self-regulation: development and psychometric analysis.
AB  - This paper describes the development and initial psychometric evaluation of a
      measure of individual self-regulation in the maintenance of health behavior
      change. Items were developed from inductively generated data to index dimensions
      of self-regulation in behavioral change (Fleury, 1991). Quantification of Index
      of Self-Regulation (ISR) content validity was supported through the ratings of 10
      experts, following criteria established by Imle and Atwood (1988). The instrument
      was tested in successive steps with 146 individuals who were participating in an
      outpatient cardiac rehabilitation program for reliability and validity, including
      internal consistency reliability and three forms of validity assessment (content
      validity, criterion-related validity, and construct validity). The three
      subscales of Stimulus Control, Reconditioning, and Behavioral Monitoring
      demonstrated internal consistency ranging from .73-.76. Total scale alpha was
      .87. Initial estimates of criterion-related and construct validity were
      documented with correlations between ISR subscales and theoretically related
      criterion measures (.20-.47). With refinement the ISR will provide a basis for
      tailoring and evaluating clinical interventions designed to enhance motivation in
      the maintenance of health behavior change.

PMID- 9769609
TI  - Measurement characteristics of the levels of institutionalization scales:
      examining reliability and validity.
AB  - The Level of Institutionalization (LoIn) scales were developed to assess the
      extent to which a health promotion program has become integrated into a health
      care organization. The instrument was designed specifically to measure the amount
      of routinization and niche saturation of four subsystems (production,
      maintenance, supportive, and managerial) believed to make up an organization. In
      this study, the LoIn scales were completed for diabetes programs in 102 general
      hospitals and 30 home health agencies in Maryland and Pennsylvania. Reliability
      estimates across the four subsystems for routines (alpha = .61) and for niche
      saturation (alpha = .44) were substandard. Average correlation among the four
      subsystems for routines was .67, and among the four subsystems for niche
      saturation was .38, indicating moderate to large amounts of shared variance among
      subsystems and challenging claims of discriminant validity. Given these large
      correlations and a poor fit when testing the eight-factor model, higher-order
      confirmatory factor analyses were carried out. Results supported the existence of
      two second-order factors. When collapsed into two factors, the reliabilities were
      adequate (routines alpha = .90; niche saturation alpha = .80). Criterion-related
      validity also was found between length of program existence and the routine
      factor.

PMID- 9769610
TI  - An abilities assessment instrument for elderly persons with cognitive impairment:
      psychometric properties and clinical utility.
AB  - In this article the psychometric properties of an Abilities Assessment Instrument
      (AAI), developed to assess the self-care, social, interactional and interpretive
      abilities of older people with cognitive impairment (CI) related to dementia, are
      described. The sample consisted of 112 institutionalized older men with CI and 60
      institutionalized older men without CI. The psychometric evaluation of the AAI
      indicated that: (a) it is reliable in terms of test-retest (Pearson's r range .93
      .99), interrater (Pearson's r range .95- .99), and internal consistency
      evaluations (Cronbach's alpha .90-.98), as well as through confirmatory factor
      analysis; and (b) that it is valid with respect to content validity (CVI 87.3%),
      concurrent validity (Pearson's r correlations ranging from -.67-.80 on the London
      Psychogeriatric Rating Scale [LPRS], and from -.76-.85 on the Functional
      Assessment Stages Scale [FAST]), and construct validity with significant
      differences between subjects with and without CI (t values ranging from 5.13
      9.30). The AAI is a reliable and valid instrument that can be used to provide
      assessment data.

PMID- 9769611
TI  - Reliability and validity of the functional performance inventory in patients with
      moderate to severe chronic obstructive pulmonary disease.
AB  - The Functional Performance inventory (FPI) is a new instrument designed to
      measure functional status in terms of activities that people perform on a daily
      basis. Psychometric characteristics were examined by a survey of 45 men and 27
      women with chronic obstructive pulmonary disease (COPD). Internal consistency
      reliability was high and no ceiling and floor effects were observed for the Total
      FPI. Concurrent validity was demonstrated by correlations with the Total Sickness
      Impact Profile (r = -.59). Construct validity was supported by correlations with
      the Medical Outcomes Study Short Form-36, Physical Functioning (r = .69), the
      Physical Activity Scale for the Elderly (r = .62) and American Thoracic Society
      Division of Lung Disease Breathlessness scale (r = -.62). The Total FPI is a
      reliable and valid measure of functional performance in persons with COPD.

PMID- 9769612
TI  - Development and validation of the avoidance of environmental tobacco smoke scale.
AB  - The Avoidance of Environmental Tobacco Smoke (ETS) scale is a self-report measure
      of the avoidance of ETS by young adults. Initial use of the scale with 30
      undergraduate students showed an internal consistency of .84 across 40 items and
      .90 in a refined 28-item instrument. In a sample of 241 students, a 20-item scale
      had an internal consistency reliability of .94 and a refined 10-item scale had an
      internal consistency of .86. In a sample of 95 mothers with a mean age of 36, the
      10-item scale had an internal consistency of .81. In three distinct samples,
      significant known groups' discrimination was found between smokers and
      nonsmokers. Psychometric analysis indicates that the scale merits further testing
      using a more heterogeneous sample from community and clinical populations to
      ensure its usefulness by clinicians and researchers interested in explaining,
      predicting, and preventing exposure to ETS.

PMID- 9769613
TI  - The development of a measure of public health nurses' practice responses to women
      who are abused.
AB  - The Public Health Nurses' Responses to Women Who Are Abused (PHNR) scale was
      designed to measure the degree of nurses' helpfulness to women who are abused by
      their partners. The measure utilizes two vignettes of nursing practice
      situations. A factor analysis of the original 30-item scale found that 20 items
      loaded on one factor (n = 125). This revised 20-item PHNR demonstrated a strong
      internal consistency (alpha = .85). The two scenarios were compared over a 2-week
      time period, resulting in a moderately strong correlation of r = .74. High scores
      on the PHNR were associated with increased age, personal experience, greater
      number of years of nursing experience, and attendance at workshops on wife abuse.
      While the initial psychometric properties of the scale are supportive, further
      investigation is warranted. With this caution, the PHNR may prove useful in
      identifying nurses' skill and knowledge levels in helping abused women, and for
      pre/posttest evaluations of educational programs for nurses regarding wife
      assault.

PMID- 9769614
TI  - Audit of syringe driver use in the University Hospital of Wales.

PMID- 9769615
TI  - Re: Fentanyl, morphine, and constipation.

PMID- 9769616
TI  - Sedation for uncontrolled symptoms in a South African hospice.
AB  - The need to sedate terminally ill patients for uncontrolled symptoms has been
      previously documented in a few reports. A retrospective consecutive chart review
      was undertaken at a hospice in Cape Town, South Africa, to develop an
      understanding of the local experience and assess the potential for improved
      patient management. Twenty-three of seventy-six (30%) patients received sedating
      therapies: twenty patients for delirium, two patients for delirium and dyspnea,
      and one patient for dyspnea alone. Fourteen patients were sedated with a
      continuous subcutaneous infusion of midazolam, seven patients with intermittent
      doses of benzodiazepines, and two patients with chlorpromazine and lorazepam. The
      mean midazolam dose was 29 mg per day (median 30 mg; range 15-60 mg per day).
      Patients were sedated on average 2.5 days before death (median 1 day; range 4
      hours-12 days). The mean equivalent daily dose of parenteral morphine in the last
      week of life showed a significantly higher mean for the sedated group, as
      compared to the nonsedated group. There was minimal investigation of reversible
      causes for delirium, none of the patients underwent an opioid rotation, and the
      opioid dose was seldom decreased. None of the patients received parenteral
      hydration. The prevalence for the use of sedating treatment is consistent with
      the range of other literature reports. Nevertheless, the wide disparity in the
      reported prevalence of these problems, and the ethical concerns raised by the
      relative frequency of this sedative approach, cannot be ignored.

PMID- 9769617
TI  - End-of-life decisions and advance directives in palliative care: a cross-cultural
      survey of patients and health-care professionals.
AB  - In order to explore possible differences in the scope of end-of-life decisions
      and attitudes toward advance directives (AD) in palliative care, we conducted a
      survey of 159 patients in palliative care institutions and 93 health-care
      professionals experienced in palliative care in the United States, Germany, and
      Japan. Giving an AD in this clinical setting was considered important by patients
      and professionals. The prevalence of a formal written AD was 79% in the United
      States, 18% in Germany, and 9% in Japan. In Japan, there was a high prevalence of
      entrusting all decisions to the family (known as omakase). More than 80% of the
      patients had negative feelings toward their future decisions in the United States
      and Germany, in contrast to only 45% in Japan. Although favored by the
      professionals, there were no specific instruments for obtaining ADs. In Germany
      and Japan, some patients had given an informal AD. As a pilot content validity
      step, survey results were used to derive a checklist for content and procedural
      aspects in end-of-life decision-making. This checklist may provide the basis for
      developing an instrument to guide physicians, especially non-palliative care
      specialists, in communication with their patients and their families in this
      difficult clinical situation.

PMID- 9769618
TI  - Initial demographic, symptom, and medication profiles in patients admitted to
      continuing palliative care units.
AB  - We retrospectively reviewed 110 consecutive admissions to continuing palliative
      care units, which were designed as part of a regionalized, comprehensive
      palliative care program in Edmonton, Canada. Ninety-six patient charts met the
      criteria for evaluation. Demographic characteristics, and, when available,
      symptom profiles, cognitive status, and risk for a history of substance abuse
      were described. The medications on admission were tabulated, and in those 93
      patients who had consults done by a palliative care consultant, these are
      compared to recommended medications. This study showed an older cohort of patient
      (mean +/- SD = 75 +/- 11 years) than had previously been described in a tertiary
      unit in the same community. Median length of stay was 21 days (range, 0-> 200
      days). Cognitive impairment was higher than would be anticipated on the basis of
      age alone, with 32/47 [64% (confidence interval (CI) 55%-81%)] of patients who
      had had cognitive testing done on the day of consult being found to be
      cognitively impaired. Symptoms, as measured by the Edmonton Symptom Assessment
      Scale, were similar to those found for patients admitted to the tertiary
      palliative care unit. In the 93 patients who had palliative care consults done on
      admission, there were a total of 179 recommendations for medication or hydration
      changes. Overall compliance with these recommendations was 84% (CI, 79%-89%). The
      highest compliance was observed for recommendations to start hydration clysis
      [27/27, 100% (CI, 100%)], and the lowest rate was observed for altering or
      decreasing hypnotic medications [11/22, 50% (CI, 29%-71%)]. We conclude that the
      patients were of higher acuity than anticipated.

PMID- 9769619
TI  - Presenting symptoms in patients referred to a multidisciplinary clinic for bone
      metastases.
AB  - Symptom control is the goal of palliative irradiation. Approximately 1 month is
      required before symptomatic relief is accomplished with radiotherapy. However,
      many patients with cancer-related pain do not receive adequate analgesics, and
      opioids are often not prescribed until patients fail to respond to palliative
      irradiation. The presenting symptoms of 108 patients who were referred to a
      multidisciplinary clinic for bone metastases were evaluated with the Wisconsin
      Brief Pain Inventory (BPI). This validated instrument evaluates the severity of
      pain using a 0-10 scale; 10 represents the worst pain imaginable. The population
      comprised 65 men (60%) and 43 women whose ages ranged from 33 years to 81 years;
      median age was 55 years, and 69% of patients were less than 65 years of age.
      Despite the presence of metastatic disease, 21% of patients were working full
      time outside the home, and 6% were employed part-time outside the home; 13% were
      homemakers. Only 17 patients (16%) were unemployed. The time since diagnosis
      ranged from 2 weeks to 23 years; the median time since diagnosis was 22 months,
      and 30% of patients had been diagnosed with the past 6 months. Pain was a
      presenting symptom in 74% (N = 80) of patients at diagnosis. At its worst, the
      pain was rated as severe (levels 7-10) by 78% and intolerable (level 10) in 22%
      of the patients in the 24 hr prior to the clinic appointment. On average, the
      pain was rated moderate to severe (levels 4-10) in 79% and severe in 23% of
      patients. Only 45% of patients experienced good relief from the prescribed
      analgesics, and 23% of patients indicated that the prescribed analgesics were
      ineffective. This survey demonstrates that bone metastases incur significant pain
      that is often undertreated with analgesics before antineoplastic therapy is
      administered.

PMID- 9769620
TI  - Characterization of breakthrough pain by hospice patients and their caregivers.
AB  - This study sought to characterize the nature of breakthrough pain experienced by
      22 hospice patients and to assess the perceptions of their respective caregivers.
      Questionnaires were administered by trained hospice nurses to determine key
      elements of episodic pains in this home-based terminally ill population. Eighty
      six percent of the patients surveyed experienced breakthrough pain, with an
      average of 2.9 episodes per 24-hr period and a mean pain intensity of 7 on a ten
      point scale, compared with average baseline pain scores of 3.6 (daytime) and 2.6
      (nighttime). Breakthrough pain episodes lasted 52 min on average, with a range of
      1-240 min. The range of time to relief of breakthrough pains was 5-60 min, with a
      mean of 30 min. Caregivers' perceptions of the pain intensities, duration, amount
      of relief, and time to relief were much more likely to be inaccurate, and were
      usually underestimates. This study suggests that breakthrough pain is common in
      the hospice setting and that there is poor concordance between patients' self
      reports and their caregivers' perceptions of these pains. It is concluded that
      the pharmacodynamics of currently available oral analgesics are not well-suited
      for breakthrough pain and that better communication between patients and
      caregivers may lead to more optimal pain management.

PMID- 9769621
TI  - Sublingual morphine: efficacy reviewed.
AB  - Current guidelines on the treatment of moderate to severe cancer pain recommend
      the use of scheduled doses of opioids for persistent pain combined with "as
      needed" doses of similar agents for breakthrough pain. Oral drugs given on an "as
      needed" basis can be problematic for patients with difficulty in swallowing or
      for those who suffer from nausea and vomiting. Further, breakthrough pain can
      become excruciating in a relatively short time, a drawback for analgesics that
      require gastrointestinal (GI) absorption before pain relief can begin. Hence,
      there is considerable interest in the development of novel drug administration
      routes to provide rapid relief of breakthrough pain, particularly through a route
      that bypasses the GI system. Sublingually administered morphine has sometimes
      been used in the treatment of breakthrough pain because some believe it provides
      effective analgesia via an appropriate alternate route. Available pharmacological
      data, however, do not consistently support the rapid absorption of morphine
      through the sublingual mucosa, and clinical data concerning the efficacy of
      sublingual morphine for the treatment of cancer pain are limited, not well
      controlled, and inconclusive. While there seems to be a need for provision of
      rapid, effective analgesia to cancer patients by an alternative route, sublingual
      morphine may not satisfy this requirement. Newer formulations of analgesics
      should be tested in the treatment of breakthrough pain due to cancer.

PMID- 9769622
TI  - Methylphenidate in terminal depression.
AB  - Major depressive disorder in 26 hospice inpatients was managed with a trial of
      methylphenidate (mean daily dosage, 17.7 mg). A therapeutic response was achieved
      in 46% of the sample. However, a significant response was obtained in only 7% of
      those patients who subsequently died of their terminal illness within 6 weeks.
      Higher dosage psychostimulants may be indicated in the last weeks of life of the
      terminally ill. Alternatively "vital exhaustion" may account for the poor
      response rate in the treatment of depression in patients with advanced
      malignancy.

PMID- 9769623
TI  - Pain in Tolosa-Hunt syndrome.
AB  - Tolosa-Hunt syndrome (THS) is a condition that includes recurrent attacks of
      retro-orbital, steady, and severe pain usually as the presenting symptom.
      Symptoms may include spontaneous recurrence of pain, chronic pain, and cranial
      nerve dysfunction that are responsive to steroid treatment. A patients with THS
      is described, with findings on craniotomy and biopsy, and the typical
      presentation of acute pain and recurrence of pain associated with response to
      steroid treatment. An overview of pain in this condition is presented.

PMID- 9769624
TI  - Kentucky physicians and politics.
AB  - Approximately 19% of Kentucky Physicians are KEMPAC members or contribute to
      state legislative and Gubernatorial candidates. This limited study of political
      activity indicates that a small percentage of physicians participate in the
      political process. Despite the small number of contributors to state legislative
      candidates, KMA's legislative and lobbying effort is highly effective and members
      receive high quality service and representation in the political arena.

PMID- 9769625
TI  - Symptoms, diagnosis, and management of dysphagia.

PMID- 9769626
TI  - Potentially productive years of life lost (PPYLL) in Kentucky due to occupational
      fatalities, 1994-1996.
AB  - A population-based occupational fatality surveillance system was used to identify
      452 work-related fatalities in Kentucky over a 3-year period. Three hundred
      eighty-six workers less than 65 years old were included in this analysis of
      potentially productive years of life lost (PPYLL). A total of 9,275 years of
      potentially productive life were lost due to these occupational fatalities,
      costing the state economy $148 million in lost wages. Most of this loss (70%) was
      in the industries of transportation/communication/public utilities,
      manufacturing, mining and construction. The transportation/communication/public
      utilities division alone accounted for 21.4% of the total lost earnings. The
      agriculture/forestry/fishing division exceeded all others in potentially
      productive years of life lost. However, because of its lower mean income and
      older ages at death, that division ranked fifth in lost earnings. This article
      demonstrates that prevention resources should be directed at the agriculture,
      transportation, and logging industries, and to the prevention of fatalities
      caused by tractors, motor vehicle crashes, and falling objects, to be most
      effective in reducing the enormous economic burden of occupational fatalities.

PMID- 9769627
TI  - [Analysis of dermatoglyphics of the digito-palmar and plantar complex in
      families].
AB  - This research was made in order to find out if there is an inherited component
      which determines the features of dermatoglyphics by transmitting inherited
      information from parents to children. The article shows the results of a research
      into 22 quantitative features of the digito-palmar complex, and 2 features of the
      plantar area in 400 persons. No significant differences were found in the
      parameters of the observed variables between fathers and sons, nor mothers and
      daughters. The differences were found, however, between fathers and daughters,
      and mothers and sons. The analysis of the correlation coefficients within the
      families showed that only the variables TRC and TPRC have polygenic hereditary
      model. The correlative analyses have shown close links between parents and
      children, the link between parents and sons being stronger than the link between
      parents and daughters. The research has not confirmed the thesis about greater
      overlap between mother and children, than between father and children, set forth
      by Knussmann in 1973.

PMID- 9769628
TI  - [Smoking in secondary school students in Zagreb].
AB  - Prevalence of smoking was studied in two secondary schools in Zagreb. Data were
      collected from 637 pupils by questionnaires. Depending on school, between 31 to
      45% pupils smoke. Different trends were observed in boys and girls. In boys from
      the families of a higher parental education prevalence is 28%; in those from
      lower 42% (p < 0.02). Smoking in girls still increases: in both populations girls
      surpassed boys (p < 0.001): observed frequencies are 47% in lower and 40% in a
      group with higher parental education. Higher frequency of smoking was observed in
      smoking families (p < 0.001). A majority of smokers begin smoking in the last
      grade of primary school, mostly because of peer group pressure and curiosity.
      Approximately 50% of regular smokers smoke more than half a pack daily. They
      comprise 12% of the surveyed population. Smokers do not assign low risk to
      smoking any more, but knowledge about diseases connected with smoking is
      insufficient. To reduce smoking among adolescents it is necessary to create
      negative attitude toward smoking and social-resistance skills during primary
      school education.

PMID- 9769629
TI  - [Nodular lymphoid hyperplasia of the colon and terminal ileum. Case report].
AB  - A patient admitted to our hospital because of diarrhea and hematochesia is
      presented. These complaints appeared eight months before, and were not
      accompanied by other disturbances. All hematological, biochemical and
      microbiological findings were normal, but endoscopic, x-ray and histologic
      examination of the gastrointestinal tract showed nodular lymphoid hyperplasia of
      the colon and terminal ileum. Since an immunological derangement was not
      verified, this seems to be a rare benign disorder as a response to repeated
      antigenic stimuli. In our patient these were recurrent parasitoses. The treatment
      is not needed, but due to the possibility of late onset hypogammaglobulinemia.
      Long-term patient follow up is required.

PMID- 9769630
TI  - [Characteristics of immunoreactivity in neonates and young children. Review of
      the literature].
AB  - Newborns and infants are particularly susceptible to infections, and this appears
      to be due to deficient immuneresponsiveness. The survey of the pertaining
      literature (95 references) reveals the particularities of newborns' and infants'
      immune responses. After the brief survey of basic immunological terms, innate
      (natural) and acquired (specific), systemic and local (regional) immune responses
      are described. Characteristics of cellular [leukocytes, polymorphonuclears,
      neutrophils, eosinophils, mast cells, monocytes, macrophages, natural killer (NK
      ) cells] and humoral (complement system, fibronectin, C-reactive protein)
      components of innate immunity are surveyed. Follows the analysis of cellular and
      humoral participants in specific immune responses: antigen presenting cells
      (macrophages, dendritic cells), B cells (immunoglobulins), T cells (TCR-1 T
      cells, TCR-2 T cells). Finally, the characteristics of local immunity are
      described. The presented overview of the immune responses reveals a partial
      immune system's immaturity (maturational deficiency) in newborns and infants.

PMID- 9769631
TI  - [The intestinal immune system in children and their disorders].
AB  - The specificities of arrangement and normal function of the intestinal
      immunological system are presented, and non-immunological and immunological
      gastrointestinal defense mechanisms are described. Of immunological defense
      mechanisms, cellular and humoral mechanisms are described separately, and their
      characteristics in childhood are highlighted. After a general survey of the
      intestinal immunological system disorders and their role in various diseases,
      three most frequent such diseases are described in detail: food intolerance,
      gluten enteropathy and chronic inflammatory bowel disease.

PMID- 9769632
TI  - [Occupational asthma].
AB  - The definition of occupational asthma is described. Causative agents which may be
      responsible for the development of occupational asthma are listed. Among factors
      responsible for the development of occupational asthma, immunological and
      nonimmunological mechanisms are specially described. The clinical characteristics
      of the disease, diagnostic methods, differential diagnosis, prognosis and
      prevention of occupational asthma are described. Procedures for determining
      exposure, occupations in which most frequently occupational asthma can develop,
      as well as preventive measures are reported.

PMID- 9769633
TI  - [Fumonisins--mycotoxins produced by Fusarium moniliforme].
AB  - Fumonisins are toxic metabolites of the fungus Fusarium moniliforme and several
      other Fusaria that commonly contaminate corn. Only recently discovered in 1988,
      these mycotoxins appear to be causative agents of several toxicoses in animals
      that result from ingestion of moldy corn and corn-based feeds. These include
      equine leukoencephalomalacia, porcine pulmonary oedema, nephrotoxicity,
      hepatotoxicity, hepatocarcinogenicity in laboratory animals. There is also
      evidence that suggests that F. moniliforme and fumonisins may also be responsible
      for oesophageal cancer in humans in certain areas of the world where moldy corn
      is frequently consumed. Fumonisins are structurally similar to sphingosine, and
      may exert their biological activity to block enzymes sphinganine- and sphingosine
      N-acyl transferase involved in sphingolipid biosynthesis.

PMID- 9769634
TI  - [Recognition of tissue oxygen debt in clinical settings].
AB  - Despite intensive treatment, a great proportion of ICU patients is resuscitated
      incompletely. Presence of tissue oxygen debt is the crucial pathophysiologic
      element of multiple organ failure development and death in these patients.
      Parameters of oxygen metabolism, monitored in time, except prognostic value give
      us the possibility of therapeutic intervention, oriented to the prevention of
      multiple organ failure. In addition to parameters of global oxygen transport and
      utilization, gastric tonometry has been used in recent years, as a method for
      organ specific identification of tissue oxygen debt. In the article are
      considered acceptable and available options of solving this problem in everyday
      clinical work.

PMID- 9769636
TI  - [Electrophysiologic study and endocardial ECG mapping in the detection of causes
      of heart rhythm disorders].
AB  - Accessory pathways and ectopic heart focuses tachycardias are often cause of
      tachycardias. AV reentry tachycardias are great diagnostic and therapeutic
      problems. Using the electrophysiological investigation and ECG mapping, there is
      possibility to find out abnormal pathways and ectopic atrial and ventricular
      focuses. In electrophysiological investigations we can use bipolar, threepolar
      and multipolar electrodes and mapping electrodes, as well. The ablation catheter
      is introduced by transveins way in electrophysiological investigation of right
      atrium and ventricle, and via the femoral artery to the left atrium and
      ventricle. We investigated 45 patients, who are hospitalised at the Cardiology
      clinic Ependorf, of the University in Hamburg Accessory pathways were found out
      in 37 (82.22%) patients. Successful RF catheter ablation was done in 34 (91.89%)
      patients and unsuccessful in 3 (8.10%). Ectopic focuses were found out in
      patients with left ventricle aneurysm. It was indication for aneurysmectomia in
      two cases and for implantation of antitachycardia pacemaker in one case.

PMID- 9769637
TI  - [Evaluation of monitoring the efficacy of phenobarbital as an anticonvulsant
      agents using the fluorescence-polarization immunoassay].
AB  - Estimation of the monitoring efficiency of Phenobarbital as anti seizure agent
      was performed by using fluorescence-polarization immunoassay on analyzer ABBOTT
      TDx. Determined values have shown that Phenobarbital monitoring is extremely
      important in the prevention of epileptic seizures, especially considering its
      ability to induce a microsomal drug-metabolizing system.

PMID- 9769638
TI  - [Oral drug therapy options in the treatment of erectile dysfunction].
AB  - The erectile disfunction (ED) represent a disease where diagnostic and therapy
      are maial standardized. However in the pharmacological there exists a lot of
      administer justice and legal-insurent problems because there are to few
      registered medicines. In respect towards the new revolutionary development in the
      therapy of erectile disfunction, the injectionary therapy of the corpus cavernous
      loses it is permanent place. Without questions the modilities of the new oral
      therapy with sildenafil will replace many patients using the "injectionary
      therapy", concerving psychogenic, neurogenic and soft disturbance into bloodvint
      during the erection. Simply, it must be said, that there are no further results
      in the oral therapy, because of the short time research regarding sildenofil.
      Therefore it is not know what kind of side effects would resulting inffens of
      sildenafil. After taking one tablet the effects could be expected after half on
      hour. According to literature recent success with the new therapy in about 90%.

PMID- 9769639
TI  - Blood usage during wartime: the Sarajevo blood bank experience.
AB  - By this retrospective analysis about blood usage in the treatment of civilians
      and soldiers, we want to contribute to better understanding of the duties of
      hospital blood bank during the war. We have analysed medical files of 3055
      wounded and non-wounded patients (1732 civilians and 1323 soldiers) hospitalised
      at State Hospital Sarajevo in the period from May 11th 1992 to May 11th 1993
      while Sarajevo was under siege. The frequency of blood transfusion among wounded
      patients (31.3%) and non-wounded patients (22.1%) was significantly different (p
      < 0.001). The wounded patients received 1.92 blood units (modus) while non
      wounded received 1.66 blood units. The difference in blood quantity per recipient
      between wounded and non-wounded patients was significant (D = 0.267; p < 0.001).
      Out of the total number of wounded patients 48.8% were civilians. There was no
      significant difference in the frequency of blood transfusion among wounded
      civilians and wounded soldiers (30.1%: 32.5%; p > 0.20) and the same can be said
      for transfused blood quantity (D = 0.062; p > 0.05). The difference in frequency
      of transfusions among civilians and soldiers (26.7%: 30.3%; p > 0.05) are due to
      higher rate of wounded patients in the group of soldiers than in the group of
      civilians (79.2%: 57.6%; p < 0.001). In the treatment of 100 hospitalised
      patients, regarding to which group they belonged to (civilians/soldiers and
      wounded/non-wounded) an average of 61-153 blood units were used. The results of
      this analysis may help in the preparation of hospital blood banks for a
      successful functioning during the war which is characterised with massive
      injuries of the civilian population and may serve for a future comparison.

PMID- 9769640
TI  - [Cellular and humoral immunity in atopic dermatitis].
AB  - In vitro tests of cellular and humoral immunity were analysed by: T and B
      lymphocytes, T4 and T8 lymphocyte subsets, lymphocyte blast transformation tests
      with unspecified mitogenom--phytohemaglutinin, C3 and C4 components of the
      complement and circulating immune complexes at patients from 6 to 54 years old
      who suffered from atopic dermatitis without any other clinical symptom of atopy
      (so called "pure" atopic dermatitis). Parameters of cellular and humoral immunity
      were analysed in the active and quiescent phase of illness. The results were
      statistically analyzed by Student's "t" test and compared with results of the
      control group. In the active phase of illness IgE level in serum was
      statistically and significantly increased while other parameters of humoral and
      cellular immunity did not significantly differ in relation to control group. In
      certain percentage in the active phase of illness decreased values of serum's
      IgA, C3 component of the complement, number of T8 lymphocytes and lymphocytes
      transformation test were found as well as the increase of circulating immune
      complexes IgG, IgM and B lymphocyte. All laboratory tests were repeated in the
      quiescent phase of illness, when patients had no changes on the skin in at least
      one month period. It was found that some increased values of serum's IgE were
      normalised in the quiescent phase of illness. Besides increased serum's IgE in
      the active phase of illness, it was not possible to determine cellular and
      humoral immunity defect by tests in vitro at "pure" atopic dermatitis.

PMID- 9769641
TI  - [Comparative analysis of traffic accident injuries and injuries from land mines].
AB  - The observation period was from 1 January 1996 to 31 December 1997. The purpose
      of this research is to determine the frequency of the injuries (traffic's
      accidents and contact mine's) in the Emergency Medical Service at Tesanj, and
      their mutual relation. We made a protocol where we registered the personal data,
      cause, time and type of injuries, treatment and the outcome. We found out that
      0.68% of injuries treated in Emergency Department's were caused by traffic
      accidents and contact mines's) Traffic's injuries were the dominant ones (90%).
      Males were injured more often than females. Children were injured's in 18%.
      Critical month for the traffic's accidents was May, and for the injuries by
      contact mines's was April. The traffic's injuries had tendency of increase, and
      the injuries by contact mines's had tendency of decrease in comparison with cases
      in 1996. In Emergency Medical Service 92% of victims arrived in the first thirty
      minutes after injury. The accidents 's' mostly happened between 08-12 h a.m. and
      08-12 h p.m. Rarely the accidents happened between 04-08 h a.m. A head was the
      most injured body part in traffic accidents (35%) and lower limbs in the contact
      mine injuries (around 30%). At the injuries by contact mines 62.5% of amputations
      were at the level of lower leg. The mortality at contact mine injuries's was
      17.6% and at traffic injuries 2.7%.

PMID- 9769642
TI  - [Effect of coagulation and fibrinolytic changes on fetal growth in pregnant women
      with chronic hypertension].
AB  - Elevated platelet activation, fibrinogen deposition in microcirculation,
      elevation of fibrin/fibrinogen degradation products as well as the increase and
      decrease in factor VIII concentration are described in pregnancies with
      hypertension. We analyzed data from 31 pregnancies with chronic hypertension. The
      aim of this study was to evaluate effects on coagulation factors, pregnancy
      outcome and fetal growth. An evident change in coagulation factors occurred in
      pregnancies with hypertension in comparison with healthy pregnant women.
      Statistically significant coefficient correlation between fetal growth and
      fibrinolysis were obtained (r = 0.3; p < 0.004). With fibrinolysis slowing down a
      higher birthweight occurred. Birthweight showed correlation with coagulation
      factor VIII (r = 0.21; p < 0.03).

PMID- 9769643
TI  - [Significance of active and passive drainage methods on healing after use of
      internal osteosynthesis (animal experiment)].
AB  - The results of healing by osteosynthesis at dogs' bones fractures are presented
      in this paper. The importance of drainages is emphasised in the healing process.
      In Cantonal veterinary station in Sarajevo in the period January 1995-January
      1998, 14 dogs with osteosynthesis were selected. We observed the following
      parameters: wound's healing, functional status, X-ray examination. In respect of
      the incidence of complications in the final results of healing there were no
      evident differences between these two groups with active drainage A and passive
      drainage B.

PMID- 9769644
TI  - [Information on the use of the DRG system in health care in Bosnia-Herzegovina].
AB  - Improvement of the efficiency and effectivity of health care system is a task of
      high priority for social system because it is one of its crucial components.
      Health care system spends significantly great part of social budget. That is why
      its quality--directly or indirectly--influences other segments of social system.
      After five years of either total or partial destruction of health care
      capacities, facilities, resources, lack of human resources, as well due to total
      collapse of the economy in our country, the consequences of the aggression on
      Bosnia and Herzegovina require radical changes in respect of the organisation and
      structure of the health care system in Bosnia and Herzegovina. Concerning the
      fact that hospital system in Bosnia and Herzegovina is one of the most expensive
      segments of health care system, future reforms in health care system should be
      implemented primarily in this field. These reforms should consist of establishing
      of DRG system for control, evaluation, updating, financing and management of
      health care system to desired direction and way of development. In that regard,
      it is necessary to: improve actual computer capacities by application of new
      technologies; develop DRG and CASEMIX classification systems, following
      experiences of highly developed countries, and adapt it to our health care
      system; change financing system by following CASEMIX, and adapt CASEMIX step-by
      step to implementation i.e.: department by department; hospital by hospital; in
      the last phase-to connect CASEMIX with network of integral information system of
      Sarajevo Canton and, later, with network of all other cantons in BiH. to educate
      medical staff about the implementation and use of DRG and CASEMIX in practice.

PMID- 9769645
TI  - [Stomatologic aspects of radiotherapy of head and neck tumors].
AB  - Therapeutic x-irradiation of the oral cavity and the oropharynx is associated
      with tissue reactions and complications. From dentists view the most important
      are radiation-induced tooth decay and periodontal disease, xerostomia and
      osteoradionecrosis from postradiation therapy extractions. In the paper are
      discussed radiobiological basis for oral cavity tissue reactions and
      pathophysiology of secondary complications. Finally, recommendations for
      prevention of oral complications and dental care are given.

PMID- 9769646
TI  - [Indications for supragingival preparation of teeth for placement of fixed
      prostheses].
AB  - Supragingival preparation offers simple controllable preparational procedure
      without contact of boring machine with gingive. That is the way to avoid the
      initial lesion of marginal parodont. The exactivity of leaning of the crown edge
      is visible. The control of generation of a carious initial lesion is in domain of
      patient--the carer and doctor. The esthetic aspect of work is not endangered by
      placing the crown of teeth of molar and premolar regions. The position of the
      edge of a crown makes possible the complete control and carrying out the measures
      of oral hygiene. The usage of monocomponent esthetic resins can solve the
      question of esthetic moment in the area of cement fissure. Supragingival location
      of the crown edge makes possible the inspection control of preparational border,
      the edge closing, esthetics in the tooth area and initial carious lesions.

PMID- 9769647
TI  - Genetics of mood disorders--an overview. Part one.
AB  - Mood disorders are severe and common psychiatric diseases with two main clinical
      forms: Bipolar disorder, type 1 (BP1), and Unipolar disorder (UP). This paper
      provides an overview of the Literature on genetics of BP1 and UP disorders. We
      described the problems of diagnostic definitions, and statistical methods for
      studying the genetic etiology of these disorders. Epidemiological and
      quantitative genetic studies are reviewed. Interactions of susceptibility genes
      and environmental factors in this disorders are also fundamental and has to be
      properly investigated. The understanding of genetic aspects of BP1 and UP
      disorders has benefited from recent findings with DNA markers. Therefore we also
      provide an overview of linkage and association studies that reveal several
      chromosomal regions, candidate genes and dynamic mutations which may play role in
      BP1 and UP disorders.

PMID- 9769648
TI  - [Necrotizing fasciitis and decubitus ulcers in the ischial area].
AB  - We shall present a case of the patient with inferior paraplegia and developed bed
      sore. Complications of necrotic lumbar fascitis in femoral and gluteal region
      have occurred but the fast and radical surgical approach together with
      medicaments support lead to cure.

PMID- 9769649
TI  - Review of rabies in Europe.

PMID- 9769650
TI  - Immunogenicity of BHK-rabies vaccine in human volunteers.
AB  - The production of rabies vaccine on baby hamster kidney (BHK-21) cells for human
      use is discussed. Long term experience in application of this vaccine in animals,
      without any noticeable complications and findings of inactivation of contaminated
      DNA from the cell substrate by beta-propiolactone have justified its
      recommendation for human use. Preliminary results of applying this simple,
      adjuvant vaccine in volunteers, confirmed its good tolerability and
      immunogenicity.

PMID- 9769651
TI  - Tick-borne encephalitis and its prevention in Hungary.
AB  - Tick-borne encephalitis (TBE) has been registered in Hungary since 1977. In the
      last four years a moderate decrease of cases was observed. Most cases belong to
      the age group of 30-39 years, and the number of males is twice as high as that of
      the females among the TBE cases. The efficacy of TBE vaccination was proven also
      in field trials. The use of the specific hyperimmune gamma-globulins for
      postexposure prophylaxis is effective. The need to create an international
      standard for TBE vaccine is discussed.

PMID- 9769652
TI  - [Prevention of human rabies in Yugoslavia].
AB  - Over the last two decades human rabies prophylaxis in Yugoslavia was successful
      and not a single case of the disease was registered. However, every year there
      are registered cases of those injured by animals in which rabies was confirmed by
      laboratory evidence. In FR Yugoslavia every year 800-1000 people are vaccinated
      against rabies, which makes 10% of all the people injured by animals in
      Yugoslavia. During 1997 there were 10.266 patients injured by animals; 816
      (7.95%) were vaccinated whereas 52 were injured by rabid animals or rabies
      suspected animals; 662 were injured by unfamiliar or wild animals, while 102
      patients were injured by familiar or preventively vaccinated animals. In other
      patients vaccination was avoided by a 10-day veterinarian surveillance of the
      dog. New literature estimated application of reduced so-called "Zagreb-2-1-1"
      vaccination protocol in severe injuries as unsuccessful in children because of
      active immune response suppression by simultaneously given immunoglobulin, and
      that is why this protocol must be abandoned.

PMID- 9769653
TI  - [Epizootiologic situation of rabies in 1997. Urbanization of sylvatic rabies in
      Yugoslavia].
AB  - The Federal Republic of Yugoslavia is situated on the border of a great sylvatic
      rabies epizootics occurring in central and eastern Europe. That is the reason why
      a relatively small number of rabid animals have been registered. In 1997, 124
      rabid animals, mainly red foxes, were identified. In recent years red fox rabies
      epizootics in Yugoslavia has annually spread 15-20 km to the south. Rabies in
      domestic animals, especially dogs, was characterized with furious clinical forms
      and dog-to-dog transmission typical of urban rabies. Sylvatic rabies has been
      almost completely eradicated in some countries of western Europe in the last
      years, mostly due to the method of oral vaccination of foxes-the main vector of
      rabies.

PMID- 9769654
TI  - [Spongiform encephalopathies in animals and humans].
AB  - Spongiform encephalopathies include several diseases of animals and humans: sheep
      and goat scrapie, bovine spongiform encephalopathy (BSE). Creutzfeldt-Jakob
      disease (CJD) in humans and its new variant (vCJD). Common characteristics of
      these diseases are long-term incubation, slow and progressive course, spongiform
      changes within nerve tissue, neuron loss and astrocytosis. Causative agent
      responsible for spongiform encephalopathy is prion (PrPsc) and it represents a
      posttranslationally modified host protein (PrPc) which normally exists and is
      produced in the cells. Development of certain diseases can be influenced by
      genetic factors, because of mutations in the PrP gene. Pathogenesis of these
      diseases is still not clear. In experimental peripheral infection the ineffective
      agent is first detected in the spleen and lymph nodes, and then it neurally
      spreads to the CNS. Bearing in mind that etiology, pathogenesis and mutual
      connection of spongiform encephalopathies have not been completely explained yet,
      caution and strict veterinary and sanitary measures are of great importance.

PMID- 9769655
TI  - [Rabies in dogs and efficacy of active immunoprophylaxis in Yugoslavia].
AB  - In this study we analyzed 36 cases of dog rabies diagnosed at the Pasteur
      Institute in Novi Sad during the last 10 years as well as the quality of
      postvaccination immunity. Most dogs had the paralytic form, more common in
      sylvatic rabies than furious clinical picture. 11% of dogs were aggressive,
      whereas 44% had injured humans, including their owners. Postvaccination immunity
      was examined in a group of dogs vaccinated with three domestic and one vaccine
      imported from abroad. Vaccination was successful in more than 70% of dogs and it
      is a sufficient percentage of seroconversion in dog rabies eradication. However,
      in dogs vaccinated only once during lifetime, the immunity was not satisfactory.
      That is why in primary vaccination of dogs compulsory revaccination 30 days after
      the first vaccine dose is suggested.

PMID- 9769656
TI  - [Knowledge of rabies in schoolchildren].
AB  - Rabies is a zoonosis which rarely occurs in our country, mostly due to good
      control of this disease. In order to assess knowledge of final grade elementary
      schoolchildren about rabies, a poll was conducted in Novi Sad (town) and Curug
      (village) in 1997. Gained results show that a great number of children have
      household pets, much more in rural than urban areas. Although most children have
      knowledge about rabies prevention, knowledge of a certain number of children is
      not sufficient and they do not have proper hygiene habits in contact with
      animals. Taking into consideration the fact that dog population increases both in
      urban and rural areas, corresponding education of their owners, including
      children, is necessary. Health education is the method of choice in health
      protection and promotion of health, skills and behavior in regard to health and
      possible health risks engaged in contacts with domestic animals-household pets,
      whereas, apart from the family, the school must play an important role.

PMID- 9769657
TI  - [Clinical picture and treatment of venomous snake bites in Yugoslavia].
AB  - Snakes of the Balkan peninsula represent an important part of the fauna of this
      part of Europe. Due to its biochemical complexity, snake venom cannot be compared
      with venoms of any other venomous animals. The primary effect of venoms of snakes
      of this region (Viperina) is local (myonecrosis and hemorrhage) and hemotoxic.
      Following the bite local signs occur very soon: pain, edema, erythema, signs of
      hemolysis as well as systemic: nausea, vomiting, hemorrhages in vital organs,
      sweating, prostration. Systemic manifestations following viperine bite, edema and
      hemorrhagic complications mostly disappear within a week, while coagulation
      disorders may persist for two or three weeks. The management of snake bites
      starts with application of a specific antitoxin, in our country being produced at
      the Institute of Immunology and Virology TORLAK in Belgrade.

PMID- 9769658
TI  - [Therapeutic approach to neurocysticercosis].
AB  - Neurocysticercosis is a clinical form of parasitic infection caused by Taenia
      solium. Therapy is recommended only for the symptomatic form of illness and
      whether to apply conservative and/or surgical treatment, depends on the
      localization of the infection in the nerve tissue, the number of cysts and
      symptoms of the infection. Conservative therapy (drug therapy and supportive
      therapy) is the therapy of choice for majority of patients, while Albendazole has
      proved better than Praziquantel in many clinical trials. The recommended dose of
      Albendazole is 10-15 mg/kg/24h during 8-28 days, whereas for Praziquantel it is
      50 mg/kg/24h in three divided doses during 15 days. It is considered that
      combined therapy of Albendazole and Dexamethasone has better effects because of
      increased serum concentration of Albendazole metabolites. Implantation of
      intraventricular shunt and/or removal of cysts are surgical procedures in
      management of neurocysticercosis. Combined conservative and surgical treatment is
      most often applied in extraparenchymal forms and those parenchymal forms of
      neurocysticercosis in which symptoms persist despite antihelmintic therapy, while
      cysts are accessible for surgical treatment.

PMID- 9769659
TI  - [Dr. Adolph Hempt's visit to Paris in 1925].

PMID- 9769661
TI  - [Perspectives in internal medicine on the threshold of the 21st century].

PMID- 9769662
TI  - [Shigellae isolated in 1997--plasmid profiles and antibiotic resistance].
AB  - INTRODUCTION: Shigella spp is one of the most frequently isolated bacteria
      causing acute diarrhea with us. Genetics of pathogenicity of Shigella spp.
      includes chromosomal and plasmid genes. Most virulence factors are coded by
      invasion plasmid antigen genes residing on a 180-230 MDa plasmid. There is a big
      problem with multiple resistance of Shigella spp. strains, which is mostly
      plasmid-borne. Genetic analysis of bacterial cells, that is plasmid profile
      analysis, is important for investigation of sources and ways of spreading of the
      infection. All isolates originating from the same clone have identical plasmid
      profiles, i.e. number and size of plasmids. The aim of the investigation was:
      comparing the type of resistance to antimicrobical agents found in epidemic and
      nonepidemic. Shigella strains isolated in 1997, analyzing plasmid profiles of
      these isolates and confirming their epidemic connection. MATERIAL AND METHODS:
      Susceptibility to antibiotics was examined by a standard disc-diffusion method.
      Plasmid profiles of 40 strains (20 from the outbreak and 20 from sporadic cases)
      were tested using a method of alkaline lysis by Birnboim and Doly followed by
      electrophoresis in agarose gel. RESULTS: Shigella strains were resistant to
      antimicrobial agents which are most commonly used. Epidemic isolates shared the
      same resistance type, they were resistant to cephalexin, streptomycin and co
      trimoxazole. The dominant type of resistance of nonepidemic strains was to
      ampicillin, streptomycin and co-trimoxazole. Strains isolated during the outbreak
      had identical plasmid profiles (2 plasmid bands of 55 and 1.5 MDa). Non-epidemic
      isolates had different plasmid profiles as well as type of resistance.
      CONCLUSION: Strains of Shigella spp. isolated during an outbreak had the same
      type of resistance and the same plasmid profiles, which indicated their origin
      from the same clone. The plasmid profile analysis is a reliable and precise
      method for determination of epidemic connection of Shigella isolates.

PMID- 9769663
TI  - The concentration of immunoglobulins A, G, and M in serum of patients with
      periodontal disease.
AB  - The aim of this study was to assess if there are any significant differences of
      immunoglobulin A, G and M concentration in serum of persons with different stages
      of periodontal destruction. The study comprised 30 persons (21 female and 9 male)
      with a mean age of 37.5 years, in whom periodontitis was diagnosed after clinical
      examination and x-ray analysis. After that the selection of patients was made
      according to the following criteria: 1. no systemic disease; 2. no basic
      periodontal therapy undertaken in the last three months; 3. presence of at least
      20 teeth; 4. no antibiotics taken in the last three months. The control group
      consisted of 30 healthy persons with a mean age of 23.0 years in whom healthy
      periodontium was diagnosed after clinical examination and x-ray analysis, and
      only 1, 3 and 4 of above-mentioned criteria had to be fulfilled. The seversity of
      clinical gingival inflammation was determined by gingival index after Loben (5).
      The severity of periodontal destruction was assessed by measuring the pocket
      depth. The immunoglobulin A, G and M concentration in serum was determined by
      method of nephelometry on the day obtaining the sample. The mean values of
      immunoglobulin A, G and M in serum of patients with periodontitis were in normal
      ranges and not significantly different compared to the control group (p > 0.05).
      There is no relationship between the serum immunoglobulins A, G and M and
      severity of gingival inflammation and periodontal destruction.

PMID- 9769664
TI  - [A theoretical approach to health and its measurement].
AB  - INTRODUCTION: For a long period of time analyses of health status have been based
      on mortality data, while in this century indicators of morbidity have been
      introduced as well. However, these two indicators also have limitations because
      health of the total population was estimated on the basis of data referring to
      the diseased or deceased during a certain period of time. The definition of
      health by the World Health Organization was a progress, because the medical model
      of health was extended to the sociological model with emphasis on well-being,
      achievement of goals, functioning in the society and social rules. Subjective
      interpretation of health also has a significant place in assessment of health
      status of an individual or population groups. CONCEPTION OF HEALTH: Health has a
      subjective and an objective dimension. It can be analyzed as a global quality,
      but also as a sum of specific qualities--physical, social and psychological.
      Health analyses include the following parameters: mental well-being (affective
      status, mental functioning), physical health (ability to proceed with activities,
      body integrity, general physical capacity), general well-being and functioning
      (perceiving general health and expectations in regard to health in the future).
      Health is a prerequisite of social and economic status, and that is why emphasis
      is on social adaptation, but social support as well. HEALTH MEASUREMENT: Health
      measurement can be functional with diagnostic, prognostic or evaluation purpose.
      Health indicators can also be descriptive, focused on a certain organ, diagnostic
      methods, but complex as well measuring syndromes, global health and quality of
      life. Development of health promotion and programs of disease prevention, follow
      up of their application, progress and results require various categories of
      measurement. Some of them identify or quantify the problem, others describe the
      determinants. There exists a need to measure the contents and processes of
      intervention and evaluation. Numerous scales of health measurement, that is
      different aspects of health and quality of life, have been developed, but many of
      them have limitations, particularly concerning validity and reliability.
      CONCLUSIONS: Most of existing indicators reflect the model of disease, while
      contemporary approach to health deals primarily with health itself. This model is
      oriented towards everyday life and relationships between individuals or groups of
      people and their physical and social environment as well as towards the way they
      influence health and well-being. The model also emphasizes well-being,
      achievement of goals, functioning in the society and social roles. Subjective
      assessment of health is significant in evaluation of health status, that is
      quality of life in regard to health, which is being done by different scales. The
      development of such scales is slow due to different opinions concerning the
      definition of health and health measurement. Efforts to develop scales which
      would satisfy the basic characteristics of measurement have largely focused on
      validity, reliability, accuracy, sensibility, specificity and feasibility.

PMID- 9769665
TI  - [Gamma aminobutyric acid--its function, disorders and their sequelae].
AB  - Gama-Aminobutyric acid (GABA) is an important neurotransmitter that mediates
      inhibition in the central nervous system. Approximately 30-50% of all synapses
      are defined as GABA-ergic. GABA is a neurotransmitter in cortical and hippocampal
      interneurones. GABA-RECEPTORS: Till today, three receptor subtypes have been
      known: GABAA, GABAB and GABAC, which are pharmacologically different. GABAA
      receptor is postsynaptic and localized in central and peripheral sympathetic
      neurones. Its agonist is muscimol and is antagonized by bicucculline. GABAB is a
      presynaptic receptor of vegetative and central nerve terminals. Its agonist is
      baclofen. The main difference between these two subtypes is that the first one
      acts directly on Cl ionphore, while GABAB activity is mediated by Gi protein.
      GABAC receptors are the integral part of the membrane, which stabilise the
      resting potential of the cell by increasing conductivity for Cl. Their most
      effective agonist is TACA. GABA ACTIVITY ON SYNAPSES: GABA is the most powerful
      inhibitory neurotransmitter in CNS. Synaptic inhibition decreases cell's ability
      to communicate with other cells and it is realised by various inhibitory
      mechanism of GABA, such as preventing of stimuluss generation, dendritic
      inhibition and dendro-dendritic inhibition. GABA AND NEUROENDOCRINE REGULATION:
      Besides physiological significance in maintaining regular excitation and
      inhibition balance. GABA plays an important role in neuroendocrine regulation of
      the following hormones: LH, FSH, PRL, STH, SS, ACTH, TSH, TRH, MSH, VP and OX.
      GABA IN NEUROLOGICAL DISEASES: Increasing or decreasing of GABA-ergic tone, due
      to different reasons, may lead to numerous neurodegenerative disorders (epilepsy,
      hepatic encephalopathy, Huntington's chorea, spinocerebellar degeneration,
      dementia and psychosis).

PMID- 9769666
TI  - [Perinatal infection with the human immunodeficiency virus].
AB  - INTRODUCTION: HIV infection, eventually resulting in AIDS, represents an
      important problem of the present days, whereas statistical parameters
      corresponding with the incidence of its manifestations and lethal outcome deserve
      great attention and cause anxieity of both general population and medical workers
      of all profiles. The problem is particularly complicated in the HIV-infected
      pregnant women. The aim of this paper is to examine epidemiology of HIV and AIDS,
      influence of HIV infection on the course and outcome of pregnancy, ways of
      transmission of HIV infection from mother to child, possible effects of
      progression of HIV infection and medical procedures and approaches in HIV
      infected pregnant women. CLINICAL MANIFESTATIONS AND OPINIONS: Some studies from
      North America and Europe demonstrated an adverse effect of HIV-1 infection on
      pregnancy outcome, others failed to confirm these findings. Most studies from
      Africa describe an untoward effect of HIV-1 infection on pregnancy outcome,
      including fetal wastage, prematurity, low birth weight, stillbirth and neonatal
      death, but not in terms of embryopathy or congenital abnormalities. The incidence
      of perinatal transmission varies from 13% and 48%, 13% to 32% for the developed
      world and 25% to 48% for developing countries. Transmission can take place
      antepartum, during delivery and postpartum by breastfeeding. Transmission during
      the first trimester may take place but current data suggest that a substantial
      proportion of perinatal HIV-1 transmissions take place rather late in pregnancy
      or during delivery. The apparent absence of viral genome from fetal tissue,
      presence of a normal immune system at birth, absence of neonatal morbidity and
      reports of differential viral transmission in twins are arguments in favour of
      late transmission. One of the greatest concerns for both women and their
      physicians is the possibility that pregnancy may accelerate the onset of AIDS in
      mother. Pregnancy itself can be immunosupressive and some investigators have
      hypothesized that the cumulative immunosupressive effect of HIV-1 infection and
      pregnancy may accelerate the course of HIV-1 infection in pregnant women.
      Counselling of HIV-positive women worldwide in regard to their HIV serological
      status has not proved to influence most women's attitudes towards their
      subsequent reproductive behaviour. MANAGEMENT AND PREVENTION: HIV-infected women
      should be offered a possibility of an abortion. Ongoing pregnancies should be
      carefully monitored and CD4 lymphocyte subsets examined at booking. If the CD4
      count is below 200 cells/mm, prophylaxis Pneumocystis carinii and Zidovudine
      therapy should be initiated. Prevention includes changes of behaviour such as
      reduction of the number of partners, condom use and early and appropriate
      treatment of sexually transmitted diseases. Antiviral therapy at birth may
      prevent this type of HIV-transmission. Also vaginal lavage with virus
      inactivating products such as chlorhexidine has to be assessed as a possible
      intervention. Prevention of phase 3 transmission (by breast milk) primarily
      involves recommendation for seropositive mothers not to breats feed their
      children. Contraceptives should be strongly advocated as soon as possible after
      giving birth. CONCLUSION: HIV infection, reproduction and motherhood jeopardize
      millions of women worldwide. The most appropriate approach in preventing
      perinatal transmission involves preventing HIV-1 infection in women of
      childbearing age, including sexual education nd condom promotion at a very young
      age.

PMID- 9769667
TI  - [Clinical characteristics of unipolar and bipolar depression].
AB  - INTRODUCTION: In the last decades affective disorders were divided into unipolar
      and bipolar and this division has been generally accepted. The bipolar type is
      manifested by mania or by both mania and depression. On the other hand, unipolar
      affective disorders are manifested only by depression. In numerous investigations
      authors have noticed that there are very distinctive differences between these
      two types of depressive disorders such as: course of illness, personality
      disorders, sex, family history etc. Nevertheless, in practice it is often very
      difficult to make the right diagnosis. The bipolar type often starts with a few
      pure depressive episodes and sometimes mania occurs a few years later so only at
      that point the psychiatrist can make the right diagnosis and treat the patient
      correctly. MATERIAL AND METHODS: This investigation comprised 50 patients
      hospitalized at the Psychiatric Clinic in Novi Sad during 1992-1995. The
      experimental group consisted of 20 patients with a bipolar affective disorder
      (according to ICD-X), while the control group consisted of 30 patients with
      clinical diagnosis of unipolar depression (intensive, without psychiatric
      features). Both groups of patients were weekly evaluated by Hamilton Depression
      Rating Scale (HDRS), whereas the initial score for all patients had to be higher
      than 16. RESULTS: Patients suffering from unipolar depression were older than
      patients with bipolar depression and there were more females in this group. There
      were no differences in demographic characteristics (level of education,
      migration, etc.), but the experimental group had a greater genetic loading for
      affective disorders. Unipolar depressive patients had more agitation and they
      were more anxious than patients with bipolar depression. DISCUSSION AND
      CONCLUSION: The fact that unipolar depressive patients were older than bipolar is
      similar to most of the results gained in this kind of investigation. On the other
      hand, we did not find statistical differences in the intensity of disorders, and
      in the literature these results are contraindicating. Numerous investigators
      report that bipolar depressives had a stronger genetic loading for affective
      disorders and our study confirms the same. All these results can help us to make
      the right diagnosis of unipolar and bipolar affective disorders.

PMID- 9769668
TI  - Monitoring of serum concentrations of antibiotics by microbiological method: a
      one-year experience.
AB  - By monitoring serum concentrations of antibiotics one may have an opportunity to
      make optimal adjustment of dosing regime for each individual patient, resulting
      in therapeutic concentrations in tissues and avoiding their cumulation and thus
      side effects in the organism. Concentrations of gentamicin, amikacin,
      streptomycin, ceftriaxone, benzylpenicillin, clindamycin and lincomycin were
      measured in serum of 110 patients by microbiological agar cup method. The
      measurements were made only after establishment of steady-state. Current dosing
      regime of gentamicin gave systematically subtherapeutic serum concentrations,
      while usual doses of amikacin and streptomycin achieved serum concentrations
      slightly lower than minimal toxic concentrations. Three patients actually had
      toxic serum concentrations of amikacin. Current dosing regime of penicillin
      produces therapeutic serum concentrations. The results of our study recommend
      monitoring of serum concentrations of antibiotics by a microbiological method in
      patients not responding to antibiotic therapy or having insufficiency of
      excretory organs.

PMID- 9769669
TI  - [Therapy of Helicobacter pylori infection using Lactobacillus acidophilus].
AB  - INTRODUCTION: In vitro experiments with Lactobacillus acidophilus have revealed
      its inhibitory effect on Helicobacter pylori and its application in treatment of
      Helicobacter pylori positive gastritis was examined. MATERIAL AND METHODS: 15
      patients have undergone gastroscopy with biopsy and by histopathological
      examination. Helicobacter pylori positive gastritis was detected. During a two
      month period these patients took acidophilus milk (3 x 250 ml a day) prepared
      according to a special protocol and which contained 4 x 10(9)-1 x 10(10) live
      cells of Lactobacillus acidophilus at the moment of preparation. Lactobacillus
      acidophilus strain NAS, gained from lyophilized preparation Bio-Nate (Natren Inc.
      USA) was used as a test organism. Control gastroscopy was performed 2 months
      later. RESULTS: 14 patients have completed the examination. All of them were
      satisfied with the taste of acidophilus milk and could stand it well, whereas in
      6 out of 14 Helicobacter pylori was eradicated. DISCUSSION: Helicobacter pylori
      eradication therapy is recommended in all cases of Helicobacter pylori positive
      gastritis associated with peptic ulcer, as well as in absence of ulcer when
      subjective difficulties occur. Antibiotic therapy is often unsuccessful and most
      often associated with risks of significant adverse effects, being the consequence
      of intestinal microflora disorders. The aim of using Lactobacillus acidophilus in
      the therapy is to reduce risks of adverse effects. In our study, by using
      acidophilus milk only, without other therapy, eradication of Helicobacter pylori
      was achieved in 6 out of 14 patients. All patients could stand the therapy well
      and were satisfied with the taste of the preparation. The number of examinees was
      small in regard to making conclusions, but the results are encouraging and show
      that apart from established in vitro effect. Lactobacillus acidophilus has a
      potential in vivo effect.

PMID- 9769670
TI  - [Premature rupture of the fetal membranes--an active or expectant approach in
      management of this obstetrical problem].
AB  - INTRODUCTION: A prospective investigation and comparative analysis of clinical
      and microbiological results have been performed as to point to some facts of
      possible significance in solving the dilemmas concerning the problem of pregnant
      women with premature rupture of the membranes. MATERIAL AND METHODS: Intensive
      clinical monitoring of the course, methods and complications of the labor was
      undertaken in 75 pregnant women with premature rupture of the membranes and term
      delivery. Smears from the vagina, cervix, amnion and amniotic fluid were obtained
      from each pregnant woman, as well as nasal and throat smears from newborn infants
      in order to microbiological analysis. According to the method of labor treatment,
      the investigated patients (n = 75) were distributed into 2 groups. Early
      induction of labor was applied in 39 pregnant women (labor induction 6 h
      following rupture of the membranes) and expectatively treated 37 pregnant women
      (the control of pregnant women until initiation of the spontaneous contractions
      associated with antibiotic prophylaxis). RESULTS AND DISCUSSION: Duration of
      labor (period from rupture of the membranes to the delivery and from the
      initiation of regular contractions to the delivery) was significantly shorter (p
      < 0.01) in the induced labor group. Cesarean section was performed in 18.4% od
      labors in the first and in 13.5% of labors in the second group. Chorioamnionitis
      occurred in 7.9% in the first and in 21.6% in the second group during the labor
      (p < 0.05). The incidence of puerperal and neonatal infection was lower in the
      first investigated group (7.9% and 5.2%) than in the second group (18.9% and
      16.2%). Positive microbiological finding was recorded in 13.2% of pregnant women
      from the first group and in 27.0% from the second group (p < 0.05). CONCLUSION:
      From the medical point of view it is reasonable to apply early induction of labor
      in pregnant women at more than 34 weeks' gestation. In pregnant women of less
      than 34 weeks' gestation, the expectant management of labor is recommended only
      in the next 48-72 hours.

PMID- 9769671
TI  - [Fournier's gangrene associated with carcinoma of the colon].
AB  - BACKGROUND: A case of Fournier's gangrene associated with colon carcinoma was
      reported. Fournier's gangrene is a progressive soft tissue infection of the
      perineal and scrotal region. CASE REPORT: A 50-year-old man was transferred to
      our hospital with clinical signs of septic shock and necrotizing soft tissue
      infection, of the scrotal and perianal regions. Local examination revealed a
      communication between rectum and left ishioanal fossa, many openings in the skin
      with purulent discharge and crepitus. After resuscitation the patient underwent
      emergent operation. Surgical debridements were performed. The wounds healed well
      with good granulation tissue. DISCUSSION: The majority of patients with
      Fournier's gangrene are immunocompromised. Malignant disease, obesity, diabetes
      mellitus and peripheral vascular disease have been cited as the main predisposing
      factors. The origin of this synergic infection is in alimentary and urinary
      tract. As a rule, penis, testes, bladder and rectum are spared. Conventional
      treatment includes repeated surgical debridement, special antibiotic regimen to
      cover both, aerobes and anaerobes, and intensive care treatment. Despite optimal
      medical and surgical management the mortality rate in Fournier's gangrene still
      remains high.

PMID- 9769672
TI  - [Agranulocytosis as a complication of acute infectious mononucleosis].
AB  - INTRODUCTION: Acute infections mononucleosis is the most common clinical
      manifestation of primary Epstein-Barr virus (EBV) infection occurring during
      adolescence. It is a benign lymphoproliferative, usually self-limiting disease.
      Complications are relatively rare, but they may occur, especially hematological.
      Most common are autoimmune hematolytic anemia and thrombocytopenia, and they
      respond to corticoid therapy. Deuteration of white blood cells is rather rare,
      whereas mild neutropenia is a normal finding during the course of acute disease.
      On the other hand, agranulocytosis is extremely rate, and almost every case has
      been reported in the literature. Filgrastim--the recombinant human granulocyte
      colony-stimulating factor (G-CSF) stimulates the activation, proliferation and
      maturation of progenitor granulocyte cells. This drug is usually applied in
      treatment of iatrogenic neutropenia, during chemotherapy of malignancies and in
      some idiopathic and cyclic neutopenias. CASE REPORT: A female patient, 18 years
      of age, has been hospitalized at the Clinic of Infectious Diseases in Novi Sad on
      two occasions. First because of severe acute infectious mononucleosis with acute
      hepatitis and jaundice 10 days after onset of symptoms. Physical examination
      revealed severe intoxication, dehydration, icteric skin, mucosis and massive
      hepatosplenomegaly. The diagnosis was confirmed by ELISA IgM, EBV VCA positive
      and ELISA IgG EBV VCA and IgG EBVNA negative results. The patient was discharged
      from hospital after 24 days without complaints and with normal physical and
      laboratory findings. For several days she felt well, but gradually severe fatigue
      and malaise occurred and she became febrile again. That was the reason why she
      was hospitalized again, two weeks later. This time she was febrile, extremely
      intoxicated with general lymphadenopathy, catarrhal gingivostomatitis and massive
      splenomegaly. The first laboratory findings showed severe neutropenia (absolute
      count of granulocytes was 0.156 x 10/l, with only 12% segmented neutrophils).
      Mild anemia--3.05 x 10/l was also registered, while the platelet count was
      normal. Other biochemical analyses were normal, the Coombs' test negative, while
      the serological response was also normal. Bone marrow puncture was performed and
      normocellular bone marrow was registered, somewhere hypercellular due to
      hyperplasia of granulocyte progenitor cells from promyelocytes to normal
      maturated cells. Anemia showed megaloblastoid proliferation, while megakaryocytes
      were normal. High doses of corticosteroids were applied (dexamethasone 160 mg
      daily) and filgrastim 5 micrograms every other day. From the very beginning of
      therapy the patient felt better, whereas granulocytes responded with elevation as
      soon as 48 hours after initiation of therapy. On the sixth day the treatment was
      stopped because the level of granulocytes was normal and the patient has
      completely recovered. She was discharged from hospital 4 weeks later with mild
      meteorism, but normal physical and laboratory findings and mild splenomegaly
      registered only by ultrasonography. DISCUSSION: During the last 10 years only
      several cases of severe leukopenia with acute infectious mononucleosis had been
      reported in literature. In all cases it was associated with some other
      hematological complications and it occurred in young adults without previously
      registered immunodeficiency. We have no knowledge about application of filgrastim
      in treatment of EBV-induced agranulocytosis, but the International Association
      for Studying Agranulocytosis and Aplastic Anemia reported that in 4% of patients
      Epstein-Barr virus can cause agranulocytosis even a year after the occurrence of
      acute disease.

PMID- 9769673
TI  - [100 years since the birth of Academician Petr Kuzmic Anohin].
AB  - This paper provides a brief biography of an outstanding physiologist and
      academician Petr Kuzmich Anokhin. With his functional system theory, academician
      P. K. Anokhin was the first to introduce a systematic approach to discussing
      functioning of an organism. Principles of functional systems have been applied in
      technical systems as well.

PMID- 9769674
TI  - [Remembering the first successful bone marrow transplantation performed in 1977
      in Novi Sad].
AB  - The author describes circumstances under which a young man with a severe
      idiopathic aplastic anemia, pancytopenia and hemorrhagic syndrome had undergone
      the first successful bone marrow transplantation performed at the Department of
      Haematology of the Internal Clinic in Novi Sad in 1977. As the patient did not
      react to the androgenic therapy and he had a healthy twin-brother with the same
      blood group and HLA system and MCL, differing only in Rh genotype, bone marrow
      transplantation was suggested. Attempted transplantation without
      immunosuppression and with a small number of bone marrow cells was performed in
      1976 at the Military Medical Academy (MMA) in Belgrade, but it was unsuccessful.
      The patient suffered from a serious pancytopenia and hemorrhagic syndrome, and
      survived due to blood transfusions. There were 56 blood transfusions with more
      than 20 liters of blood. At that time bone marrow transplantations were not
      performed in Yugoslavia, only MMA started this method. The patient could not be
      transported, so the author with his associates decided to perform a new
      transplantation with immunosuppressive therapy with cyclophosphamide and with
      sufficient number of bone marrow cells, believing that it was the only chance
      their patient had to get better. Without special equipment, improvising a sterile
      room, the author performed a new transplantation. Two weeks later first signs of
      improvement of pancytopenia occurred, whereas after reticulocytic crisis, 45 days
      later, the number of blood cells reached normal values. On the occasion of
      examining Rh genotype of our patient it was established that, instead of previous
      Rh genotype inherited from his father, after retransplantation he had a new Rh
      phenotype acquired from his brother who inherited it from their mother. It was a
      proof that the transplantation was a complete success. On the occasion of 20th
      anniversary of that event in 1977, the whole team, which had performed the
      retransplantation, met their ex-patient. Today he is healthy, employed and a
      successful sportsman.

PMID- 9769675
TI  - [Medicinski Pregled 1926-1941].

PMID- 9769676
TI  - Adult and child abuse reporting requirements.

PMID- 9769677
TI  - Women physicians bring their leadership to new levels.

PMID- 9769678
TI  - Women physicians teach the next generation.

PMID- 9769679
TI  - Maternity and family leave policies in rural family practices.
AB  - To help recruit and retain physicians, especially women, rural family practice
      groups need to establish policies regarding maternity and other family leaves.
      Also important are policies regarding paternity leave, adoptive leave, and leave
      to care for elderly parents. We surveyed members of the American Academy of
      Family Physicians in rural practice in 1995 to assess the prevalence of leave
      policies, the degree to which physicians are taking family leave, and the
      characteristics of ideal policies. Currently, both men and women physicians are
      taking family leaves of absence, which indicates a need for leave policies.
      Furthermore, a lack of family leave policies may deter women from entering rural
      practice.

PMID- 9769680
TI  - Allergy to natural rubber latex.

PMID- 9769681
TI  - Minnesota seniors pay more for Medicare plans.

PMID- 9769682
TI  - United, Humana cancel planned merger.

PMID- 9769683
TI  - Stroke victims need to get to the hospital faster.

PMID- 9769684
TI  - Mayo develops more accurate Lyme disease test.

PMID- 9769685
TI  - Minnesota's new health care directive.

PMID- 9769686
TI  - [Current problems of antibacterial therapy].
AB  - The development of medicine has been accompanied by the increase of the
      proportion of immunocompromised patients and as a consequence of antibiotic use,
      bacterial resistance has reached an unexpected level. Along with these changes,
      we have been witnessing the rapid development of antimicrobial therapy that
      comprises several components besides the development of new molecules. The
      learning of pharmacodynamic effects of particular antibiotic classes can improve
      the efficacy of therapy and a better cure rate can be achieved in empiric therapy
      by the knowledge of risk factors and local resistance patterns. It has become
      clear that an antibiotic policy based exclusively on restriction would result in
      increased bacterial resistance rate after a temporary decrease of antibiotic cost
      and was unable to prevent the emerge and spread of multiresistant strains. The
      solution is the rational and adequate use of antimicrobials, based on the modern
      theory and practice of antibiotic policy and infection control, that cannot be
      carried out without the activities of experts in this field.

PMID- 9769687
TI  - [Current data on familial occurrence of malignant hematologic diseases in the
      County of Szabolcs-Szatmar-Bereg in Hungary].
AB  - So far the authors have observed 27 cases of accumulation of malignant
      haematologic diseases within a family in their county. They published the first
      ten cases in Orvosi Hetilap in 1992. Most often the co-existence of the diseases
      with the highest incidence (non-Hodgkin's lymphoma, chronic lymphocytic
      leukaemia, acute leukaemia) was observed, in terms of relationship mostly the
      parent--child combination was observed. Analyzing the data of parent--child
      combinations (17 cases) they can notice two remarkable trends: 1. The "malignity
      degree" of the disease appearing in the second generation is either the same or
      greater than that of the disease of the first generation (the opposite of this
      was not experienced in any of the cases!). 2. The disease of the second
      generation appears mostly at a much younger age than that of the parent.
      Consequently, they can observe a "double acceleration": the disease tends to be
      more malignant nearly in the half of the second generation patients, and the
      disease appears in the children at a much younger age.

PMID- 9769688
TI  - [The role of hyper-homocysteinemia in the etiology of some vascular diseases].
AB  - About 5% of population have a highly, while other 15% a moderately elevated
      plasma homocysteine level. Hyperhomocysteinemia may be responsible about 10-20%
      of coronary artery, 40% of cerebrovascular and 60% of peripheral vascular
      diseases. There in an inverse relationship between folate, cobalamin and
      pyridoxine intake or blood level and plasma homocysteine level. In addition, the
      intake of these three B vitamins can reduce high plasma homocysteine level.
      Folate-folic acid seems to be the most important in homocysteine reduction due to
      the compensation of thermolabile methylenetetrahydrofolate reductase
      insufficiency, however, a milder impact of cobalamin any pyridoxine (mainly
      following a methionine load test) is also proved. There are possibilities to
      reduce risk associated with elevated homocysteine: e. g. dietary supplementation
      or food fortification. In Hungary bread enriched by folic acid, cobalamin and
      pyriodixine might reduce rate of vascular diseases due to hyperhomocysteinemia.

PMID- 9769689
TI  - [Serum acid alpha-1-glycoprotein (APG) levels in gastrointestinal tumors].
AB  - Using a new microanalytical method authors investigated the AGP level in the sera
      of 41 healthy individuals and 87 patients with and without malignant diseases of
      gastrointestinal tract verified clinically by other diagnostic (image forming)
      techniques. It could be stated that serum AGP levels measured in healthy persons
      were in good agreement with the data of others, and selecting 80 mg/dl
      concentration as upper limit of normal values (cut-off level, mean + 2SD) the
      specificity of the test for a healthy population was 95 per cent. AGP content in
      the sera of patients with various malignancies of the gastrointestinal tract,
      mainly of colon and stomach was significantly higher in comparison to the healthy
      controls. On the other hand, 16 patients from 22 gastrointestinal cases without
      malignant diseases represented serum AGP concentrations within the normal range,
      while 6 patients with acute phase of inflammation had specifically elevated AGP
      levels. According to these data specificity of 72.7 per cent and sensitivity of
      78.5 per cent (for colorectal tumours 82.9 per cent) of the test were obtained in
      average for the gastrointestinal malignancies. The positive predictive value of
      the marker was 89.5 per cent. Our investigations demonstrated that a marked
      elevation of serum AGP level indicates malignant process in the diseases of
      gastrointestinal tract with high probability. Results presented here led to the
      conclusion hat determination of the serum AGP concentration performed and
      evaluated simultaneously with other diagnostic (image forming) procedures can be
      applied successfully in the recognition of gastrointestinal tumours.

PMID- 9769690
TI  - [The role of transesophageal echocardiography in the detection of coronary
      anomalies and anatomical variations].
AB  - OBJECTIVES: The aim of the study is to examine the role of transesophageal
      echocardiography (TEE) in the diagnosis of anomalies and anatomic variations of
      the coronary arteries. BACKGROUND: In the past, coronary angiography was the only
      method for diagnostic confirmation in all cases with coronary anomalies, but even
      during invasive procedures diagnostic difficulties could and can emerge. The
      different, varying origin of aberrant coronary arteries can prolong the
      diagnostic procedure, therefore can increase the irradiation time. So every
      method which seems to be suitable for diagnosis of suspected coronary anomalies
      can be helpful. METHODS: The origin and course of anomalous coronary arteries
      were studied by TEE and coronary angiography during a six-month period. RESULTS:
      We found 16 patients (2.8%) with coronary anomalies or variations by angiography,
      the diagnosis of which was technically difficult. Seven of these had TEE
      examination too. All seven anomalous origins proven angiographically and 2 of the
      2 anomalous courses in the relation to the great vessels were diagnosed by TEE.
      (In two, the left circumflex originated from the right sinus of Valsalva, in two
      we found anomalous separate origin of left circumflex coronary artery from the
      left sinus, in another two a common ostium of the left anterior descending and
      circumflex artery from the left sinus and in one an accessory artery from the non
      coronary sinus.) CONCLUSIONS: TEE in a useful test to diagnose the origin of
      anomalous coronary arteries and confirming their course in relation to the great
      arteries.

PMID- 9769691
TI  - The numerical analysis of fluid-solid interactions for blood flow in arterial
      structures. Part 1: A review of models for arterial wall behaviour.
AB  - The structural response of a large artery is characteristically complex and
      includes the highly non-linear, history-dependent response of a nonhomogeneous
      anisotropic structure undergoing finite deformations. The mechanics of the
      arterial wall has been studied for nearly two centuries. The goals of such
      research range from the desire to have a basic knowledge and understanding of the
      mechanics and physiology of this complex structure to the need for data and
      methods for the design of arterial prostheses. In this paper, the models for
      arterial wall behaviour are critically reviewed. Firstly, the structure and
      general characteristics of the arterial wall are discussed. This is followed by a
      comprehensive review of the constitutive laws. Finally, structural analyses of
      the arterial wall by mathematical and numerical methods are discussed.
      Predictions using the authors' preferred models give focus to important issues,
      and in Part 2 the review and predictions are extended to the fluid solid coupled
      situation.

PMID- 9769692
TI  - The numerical analysis of fluid-solid interactions for blood flow in arterial
      structures. Part 2: Development of coupled fluid-solid algorithms.
AB  - In this paper, the authors extend their study of wall mechanics given in Part 1
      to the overall problem of fluid-solid interactions in arterial flows. Fluid-solid
      coupling has become a specific topic in computational methods and applied
      mechanics. In this review, firstly, the effects of elasticity of blood vessels on
      wave propagation and local flow patterns in large arteries are discussed. Then,
      numerical techniques are reviewed together with the alternative coupled methods
      available in fluid--wall models. Finally, a novel numerical alogorithm combining
      two commercial codes for coupled solid/fluid problems is presented. As a
      consequence of the present studies, wall effects are now able to be included in
      predictions of haemodynamics in a clinical context.

PMID- 9769693
TI  - The post-buckling behaviour of the pressurized abdominal cavity during knees-bent
      lifts.
AB  - When a person bends over to lift an object, the intra-abdominal pressure is
      insufficient to prevent the abdominal cavity from buckling. This paper is
      concerned with estimation of the extent of buckling, its effect on the bending
      moment capability of the abdominal cavity and the stress distributions in the
      abdominal muscles. Buckling decreases the bending moment capability of the
      abdominal cavity, increases the stresses in the oblique muscles and transversus,
      and reduces to zero the stress in the rectus muscles.

PMID- 9769694
TI  - The design of a vibration transducer to monitor the integrity of dental implants.
AB  - Bone-anchored titanium implants are being used increasingly to provide support
      for prostheses replacing missing teeth in edentulous and partially dentate
      patients. A technique is required to monitor bone formation at the implant-tissue
      interface during healing, and also to check whether there has been bone loss from
      around the top of the implant. One possible method is to screw a beam into the
      implanted fixture and to measure the first flexural resonance frequency of the
      resulting system. This resonance frequency is affected by both the exposed length
      of fixture and the stiffness of the interface between the implant and the bone.
      This paper describes the design of a beam-like transducer for clinical trials of
      the technique. The sensitivity of the transducer resonance frequency to the
      changes of interest is dependent on the thickness and length of the beam element.
      However, the choice of these dimensions is constrained by the need to avoid
      closely spaced resonances. The performance of different transducer shapes and the
      influence of the thickness and length of the beam element in the transducer has
      been studied. The results have been used to finalize a transducer design for the
      clinical trials.

PMID- 9769695
TI  - The compressive strength of articular cartilage.
AB  - Articular cartilage provides the smooth bearing surfaces in freely moving
      (synovial) joints. Its mechanical properties are important because structural
      failure of cartilage is closely associated with joint disorders, including
      osteoarthritis. Some mechanical properties of cartilage are well characterized,
      but little is known about its compressive strength. A technique for measuring
      cartilage compressive strength is evaluated, and an overview of experiments which
      relate strength to stiffness and tissue hydration is given. Specimens of bovine
      articular cartilage-on-bone, approximately 15 mm square, were loaded on a
      hydraulic materials testing machine using flat impermeable indentors. Linear-ramp
      loading/unloading cycles of 1 s duration, and of increasing severity, were
      applied until failure was evident on force-displacement graphs. Some specimens
      were tested following a 30 min period of creep loading. Inkstaining and histology
      were used to locate the site of initial damage to each specimen. Specimen failure
      occurred first in the cartilage surface layer at a nominal applied stress of 14
      59 MPa (mean 35.7 MPa). Mechanical properties were little affected by specimen or
      indentor size, provided both remained within defined limits, and compressive
      strength could be measured to an accuracy of approximately +/- 5 per cent.
      Compressive stiffness was a significant predictor of strength, but only if it was
      measured at high levels of stress. Strength increased following creep-induced
      water loss, and initial mechanical damage could propagate under moderate cyclic
      loading. This technique for measuring cartilage compressive strength has
      potential for investigating the causes of cartilage failure in vivo.

PMID- 9769696
TI  - The estimation of acetabular cup wear volume from two-dimensional measurements: a
      comprehensive analysis.
AB  - This paper describes a mathematical investigation of the relationship between
      wear volume, wear depth and wear direction in acetabular components. The analysis
      takes into account the cylindrical and conical portions at the mouth of certain
      types of socket and also incorporates the effect of an initial radial discrepancy
      between the femoral head and socket. Published formulae for converting linear
      wear measurements to wear volumes are shown to be incorrect. Wear volume is shown
      to be highly dependent on the wear direction, increasing by more than 90 per cent
      over a 60 degrees range. Cylindrical and conical portions of a 22.225 mm cup may
      contribute up to about a third as much wear as the hemispherical socket. At low
      wear depths, the neglect of a radial discrepancy between the components can
      result in an overestimation of wear volume in excess of 100 per cent.

PMID- 9769697
TI  - In vitro simulation of contact fatigue damage found in ultra-high molecular
      weight polyethylene components of knee prostheses.
AB  - An in vitro simulation of fatigue loading of ultra-high molecular weight
      polyethylene (UHMWPE) knee components was carried out on a knee simulator and on
      a rolling and sliding wear tester. Tibial components for the knee simulator were
      gamma-sterilized, implantable components taken from manufacturing inventory. The
      rolling/sliding UHMWPE discs were machined from bar stock and either gamma
      sterilized in air and accelerated aged, or left as non-sterilized (controls).
      Cracking and delamination of samples that had been gamma sterilized in air and
      aged were observed in both types of tests. Contact fatigue damage was visible in
      as few as 150,000 cycles using the knee simulator at loads of 122 N (275 1b). The
      rolling/sliding samples showed signs of damage in as few as 130,000 cycles with
      an estimated stress of 15 MPa and 25 per cent sliding. However, cracking and
      delamination were not generated in the never-sterilized or recently sterilized
      controls. UHMWPE that has been gamma sterilized in air and aged is shown to be
      susceptible to contact fatigue damage. These results are important to the
      interpretation of in vitro total knee replacement simulations used to assess the
      performance of tibial bearings.

PMID- 9769698
TI  - Sliding wear studies of selected nitride coatings and their potential for long
      term use in orthopaedic applications.
AB  - In the area of orthopaedic implants, particularly total hip joint replacements, a
      metal-plastic combination is still the most popular choice consisting of a
      femoral head fabricated from 316L stainless steel, Ti alloy or Co-Cr alloy in
      contact with an ultra-high molecular weight polyethylene (UHMWPD) acetabular cup.
      It is recently considered that wear of the UHMWPE cup is of major concern.
      Generation of the wear debris can have adverse effects on the body, both
      localized and systemic. It is envisaged that wear of the prosthetic components,
      particularly those fabricated from UHMWPE can be reduced through the use of
      surface coatings. The aim of this investigation was to deposit a selection of
      refractory element nitride-based coatings (TiN, TiA1N, ZrN) onto 316L stainless
      steel substrates, using physical vapour deposition (PVD) technology and to study
      their sliding wear behaviour in contact with both UHMWPE and 316L stainless steel
      pins, using a pin-on-plate testing rig. Tests were conducted in Ringers solution
      and Ringers solution plus bone cement particles. The volume of material removed
      from the pins served as an indication of their wear behaviour. Wear mechanisms
      were identified using scanning electron microscopy. The results of these findings
      and the potential for these coatings to be used in orthopaedic applications are
      discussed.

PMID- 9769699
TI  - Salt in hypertension: physiological and molecular aspects.
AB  - Salt loading acutely or chronically raises blood pressure in susceptible
      individuals. Sodium-dependent hypertension is characterized by sympathetic
      stimulation, apparently mediated via excitation of alpha 2-adrenergic receptors
      in brainstem nuclei. At this time, it is unclear which one(s) of the three alpha
      2-adrenoceptor subtypes may be involved in this process. Although some studies
      have reported increases in numbers and/or functional responsiveness of alpha 2
      adrenoceptors in hypertensives or normotensive offspring of hypertensive parents,
      others have failed to confirm this. Genetic analysis has suggested presence of
      alpha 2-adrenoceptor gene polymorphisms in some hypertensives but the results so
      far have been inconsistent.

PMID- 9769700
TI  - Regulation of gene expression in the endocrine heart.
AB  - Cardiac growth and contractility is profoundly altered in response to various
      hormones and neurotransmitters as well as by changes in electrolyte balance,
      blood volume, and blood pressure. In turn, the endocrine heart contributes to
      body homeostasis by secreting a number of biologically active peptide hormones
      that act on several target tissues. Atrial natriuretic peptide (ANP) and B-type
      natiuretic peptide (BNP) are the major secretory products of the endocrine
      myocardium. These peptide hormones act on many target organs via guanylate
      cyclase-linked membrane receptors to produce natriuresis, diuresis,
      vasodilatation, and hypotension. ANP and BNP receptors are found on most organs
      involved in cardiovascular homeostasis (e.g., kidney, adrenal, vasculature,
      brain). They are also present in gonads and in pituitary, where they alter
      steroidogenesis and pituitary hormone secretion. Not surprisingly, changes in
      blood pressure, volume, or hormone status influence ANP and BNP expression, which
      is also altered in almost all diseases that affect cardiac function. Thus,
      studies of ANP and BNP gene expression are relevant for many clinical settings.
      Moreover, transcription of the ANP and BNP genes characterizes cardiac cells at
      very early stages of development and is tightly linked to cardiac growth--be it
      proliferation, as in the fetal heart, or trophic growth, as in postnatal
      ventricular hypertrophy. Thus, analysis of the molecular circuitry that controls
      ANP and BNP expression might shed important insight into the complex regulatory
      pathways that underlie normal and pathologic heart development. Indeed, over the
      past few years, we have analysed transcriptional control of the ANP and BNP genes
      in embryonic and postnatal cardiomyocytes and in cardiomyocytes treated with
      hormones and neurotransmitters that cause cardiomyocyte hypertrophy. These
      studies have lead to the identification of distinct cis-acting DNA elements that
      modulate basal and hormone-stimulated transcription. Most importantly, the work
      also resulted in the isolation and characterization of cardiac-specific
      transcription factors that play critical roles for cardiac cell differentiation
      and survival.

PMID- 9769701
TI  - Alpha 2-adrenergic receptor subtypes: subtle mutation of the alpha 2A-adrenergic
      receptor in vivo by gene targeting strategies reveals the role of this subtype in
      multiple physiological settings.
AB  - Alpha 2-adrenergic receptors (alpha 2AARs) are coupled by pertussis-toxin
      sensitive G proteins to various effectors, including adenylyl cyclase and ion
      channels. The alpha 2AARs respond to endogenous norepinephrine and epinephrine to
      elicit a variety of physiological responses, including inhibition of
      neurotransmitter release, suppression of insulin release from pancreatic beta
      cells, activation of platelet aggregation, and contraction of arteriolar smooth
      muscle. Three distinct alpha 2AR subtypes (alpha 2A, alpha 2B, alpha 2C) have
      been characterized by both pharmacological and molecular biological approaches;
      however, the lack of subtype-specific ligands has precluded an understanding of
      the physiological relevance of each subtype. Previous studies demonstrated that
      mutation of a conserved aspartate residue in the alpha 2AAR to asparagine (D79N
      alpha 2AAR) resulted in a receptor that retained its ability to inhibit voltage
      gated Ca2+ channels and cAMP production but was unable to activate K+ currents in
      AtT20 cells (Surprenant et al., 1992). To explore the physiological role of the
      alpha 2AAR subtype and to evaluate the selectivity of alpha 2AAR effects with
      respect to various signal transduction pathways, we used gene targeting in
      embryonic stem cells to create a mouse line that expresses the mutant D79N alpha
      2AAR instead of the wild-type alpha 2AAR. We established a D79N alpha 2AAR mouse
      line and characterized various alpha 2AAR-mediated physiological functions in
      these mutant mice. Because the in vivo D79N alpha 2AAR is expressed at a reduced
      density relative to wild-type alpha 2A and is not selectively uncoupled from a
      single signal transduction pathway, our findings of losses of alpha 2AAR-mediated
      functions in the D79N mice reflect a requirement for the alpha 2AAR subtype but
      do not reveal the importance of a specific signal transduction pathway. The alpha
      2AAR subtype appears to mediate reduction in blood pressure following alpha 2A
      agonist administration as well as sedative, anesthetic-sparing, and analgesic
      responses to alpha 2AAR agonists. Therefore, the alpha 2AAR subtype appears to
      mediate a majority of the clinically relevant responses associated with alpha
      2AAR agonist treatment.

PMID- 9769702
TI  - Nitric oxide signaling: would you believe that a simple free radical could be a
      second messenger, autacoid, paracrine substance, neurotransmitter, and hormone?
AB  - Nitric oxide signaling during the past two decades has been one of the most
      rapidly growing areas in biology. This simple free radical gas with an unshared
      electron can regulate an ever-growing list of biological processes. In most
      instances, nitric oxide mediates its biological effects by activating guanylyl
      cyclase and increasing cyclic GMP synthesis. However, effects of nitric oxide
      that are independent of cyclic GMP are also growing at a rapid rate. Nitric oxide
      can interact with transition metals such as iron, thiol groups, other free
      radicals, oxygen, superoxide anion, unsaturated fatty acids, and other reactive
      species. The effects of nitric oxide can mediate important physiological
      regulatory events in cell regulation, cell-cell communication, and signaling.
      However, as with any messenger molecule, there can be too much or too little of
      the substance and pathological events ensue. Methods to regulate either nitric
      oxide formation, metabolism, or function have been used therapeutically for more
      than a century, as with nitroglycerin therapy. Current and future research should
      permit the development of an expanded therapeutic armamentarium for the physician
      to manage effectively a number of important disorders. These expectations have
      undoubtedly fueled the vast research interests in this simple molecule.

PMID- 9769703
TI  - Signaling via JAK tyrosine kinases: growth hormone receptor as a model system.
AB  - During the past 4 years, significant progress has been made in elucidating the
      earliest events following binding of ligands to members of the cytokine receptor
      superfamily. This is a rapidly growing family of receptors that currently
      includes receptors for growth hormone (GH); prolactin; erythropoeitin;
      granulocyte colony-stimulating factor; granulocyte macrophage colony-stimulating
      factor; interleukin(IL)s 2-7, 9-13, 15; interferon (IFN)-alpha, beta, and gamma;
      thrombopoietin; leptin; oncostatin M; leukemia inhibitory factor (LIF); ciliary
      neurotrophic factor; and cardiotropin-1. Despite their diverse physiological
      effects in the body, ligands that bind to members of this family share multiple
      signaling pathways. An early and most likely initiating event for all of them is
      the activation of one or more members of the Janus (or JAK) family of tyrosine
      kinases. The activated JAK kinases, which form a complex with the cytokine
      receptor subunits, phosphorylate themselves as well as the receptor. These
      phosphorylated tyrosines form binding sites for various signaling molecules that
      are themselves thought to be phosphorylated by JAK kinases, including 1) signal
      transducers and activators of transcription (Stats), which regulate
      transcription; 2) She proteins that recruit Grb2-SOS complexes, thereby
      initiating the Ras-MAP kinase pathway; and 3) insulin receptor substrate (IRS)
      proteins that are thought to regulate metabolic events in the cell. Additional
      other signaling molecules have been implicated in signaling by some cytokines,
      including protein kinase C, SH2-B beta, and intracellular Ca. This review uses
      the GH receptor as a model system for studying cytokine signaling and summarizes
      some of the data used to establish JAK2 as a GH receptor-associated tyrosine
      kinase and to identify signaling molecules that lie downstream of JAK2. Since
      these pathways are shared by multiple cytokines, this review also discusses
      factors that might contribute to specificity of response to different cytokines.

PMID- 9769704
TI  - Signaling in and regulation of ionizing radiation-induced apoptosis in
      endothelial cells.
AB  - Exposure of mammalian cells to ionizing radiation leads primarily to DNA damage
      induced cell death. The induction of apoptosis by ionizing radiation represents
      an alternative mode to cell kill. Breakdown of sphingomyelin to produce ceramide
      by activation of sphingomyelinase is one of the upstream signalling cascades
      activated in apoptotic cells in response to stimuli such as TNF. Using genetic
      models of acid sphingomyelinase deficiency, the ceramide generated by radiation
      induced activation of sphingomyelinase has been shown to serve as a second
      messenger in initiating an apoptotic response. PKC activation represents an
      upstream anti-apoptotic checkpoint at the sphingomyelinase level as well as a
      checkpoint downstream of ceramide generation. The balance between these pro- and
      anti-apoptotic systems may determine the magnitude of the observed apoptotic
      response.

PMID- 9769705
TI  - The MONA LISA hypothesis in the time of leptin.
AB  - The regulation of body fat stores is a problem of energy and nutrient balance
      that can be most readily viewed as a feedback system. Several elements are
      involved in any feedback system, including afferent signals, a controller that
      senses the afferent signals and transduces their information and then activates
      efferent controls that regulate the controlled system. The recent discovery of
      leptin has provided a major missing link in the feedback control system. This
      afferent signal is produced exclusively in fat cells of nonpregnant mammals but
      can be produced in the placenta as well. This circulating peptide has a very
      strong relationship to the level of body fat and its absence experimentally and
      clinically produces massive obesity. In the controller, or brain, several
      anatomic regions play a central role in regulating fat stores. Damage to the
      ventromedial nucleus (VMH) or the paraventricular nucleus (PVN) in the
      hypothalamus produces massive obesity in mammals and birds. Injury to the central
      nucleus of the amygala will also produce obesity. In contrast, damage to the
      lateral hypothalamus reduces body fat. The syndrome of leptin deficiency or
      defects in the leptin receptors produce a massive obesity that is metabolically
      similar to the VMH or PVN lesion syndromes of obesity, suggesting that leptin may
      have its metabolic effects through these medial hypothalamic centers. Support for
      this idea has come from studies showing that damage to the PVN or VMH will block
      the effects of leptin. A number of neuropeptides and monoamines are involved with
      modulating of food intake and fat stores. Both serotonin, acting through 5-HT2C
      receptors, and norepinephrine, acting through beta 2 and/or beta 3 receptors,
      reduce food intake. A variety of peptides also influence food intake and body
      fat. Neuropeptide Y, dynorphin, galanin, and melanocyte-stimulating hormone all
      increase food intake. In contrast, a large number of peptides--including
      cholecystokinin, corticotrophin-releasing hormone/urocortin, enterostatin,
      insulin, leptin, alpha-MSH, and TRH--reduce food intake. Chronic administration
      of neuropeptide Y, acting through Y-5 receptors, can produce chronically
      increased food intake and obesity. This syndrome is similar to the VMH syndrome
      and suggests that NPY must be acting as an inhibitor of a feeding system. The
      melanocortin receptor system may be particularly important because a mouse that
      does not express MC4 receptors is massively overweight. These central systems
      modulate food intake and fat stores by the controlled system. Glucocorticoids
      from the adrenal gland are important in obesity, since adrenalectomy will reverse
      or prevent the development of all forms of obesity. The sympathetic nervous
      system is also important because low sympathetic activity is associated with
      experimental and clinical obesity. The reciprocal relationship between food
      intake and sympathetic activity has been a robust relationship, suggesting that
      beta receptors in the periphery or brain may be involved in feeding control. In
      one model of dietary obesity resulting when animals eat a high-fat diet, the
      syndrome is blocked by inhibitory adrenal steroid activity. These animals show a
      lower level of sympathetic activity and a low level of brain serotonin. Finally,
      they show an enhanced sensitivity to essential fatty acids when these are applied
      to the tongue or given into the gut. In this chapter, the control of energy
      stores as fat is viewed as a feedback system. Leptin is perceived as a key
      afferent signal and glucocorticoids and the sympathetic nervous system through
      beta receptors as essential elements of this control system.

PMID- 9769706
TI  - The IRS-signaling system: a network of docking proteins that mediate insulin and
      cytokine action.

PMID- 9769707
TI  - Cyclic AMP, PKA, and the physiological regulation of adiposity.
AB  - The major regulator of lipolysis in white adipocytes and brown adipocytes is cAMP
      and the actions of cAMP are mediated by protein kinase A (PKA). Multiple subunits
      of PKA, including RII beta, R1 alpha, C alpha, and C beta 1, are expressed in fat
      cells but the major holoenzyme assembled under normal conditions contains RII
      beta and C alpha. Targeted disruption of the RII beta gene in mice revealed that
      both white and brown adipocytes are capable of compensating by increasing the
      level of RI alpha. Nevertheless, the mice display a lean phenotype, have an
      elevated metabolic rate due to activation and induction of uncoupling protein in
      brown fat, and are resistant to diet-induced obesity and insulin resistance.
      Although the metabolic disturbances in white and brown fat tissue may explain
      most of the phenotypic changes, the loss of neuronal expression of RII beta may
      also contribute to the alterations in energy balance. Specific neuronal defects
      have been characterized that prevent the normal changes in gene expression seen
      with drugs that act through the dopaminergic pathway. The RII beta mutant mouse
      provides an interesting model of obesity resistance and demonstrates that chronic
      changes in the PKA signaling system can lead to stable alterations in energy
      storage and utilization.

PMID- 9769708
TI  - Life without neuropeptide Y.
AB  - Neuropeptide Y (NPY), a 36 amino acid neuromodulator that is secreted by neurons
      throughout the peripheral and central nervous system, has been implicated in the
      control of many physiological processes. We have begun to examine its role in
      regulation of appetite, behavior, and excitotoxicity by examining mice that are
      unable to produce NPY as a consequence of gene inactivation. These mutant mice
      are remarkably normal when reared under standard vivarium conditions. Despite
      considerable evidence that NPY plays a central role in stimulating appetite, NPY
      deficient mice eat normally, grow normally, and refeed after a fast normally.
      Furthermore, all of their endocrine responses to fasting are normal. The response
      of NPY-null mice to diet-induced obesity, chemically induced obesity (monosodium
      glutamate and gold thioglucose), and genetic-based obesity (lethal yellow agouti,
      Ay; uncoupling protein-diphtheria toxin transgenics, UCP-DT) were all normal.
      However, NPY deficiency does partially ameliorate the obesity and all of the
      adverse endocrine effects of leptin deficiency in ob/ob mice. NPY-null mice as
      well as mice deficient in both NPY and leptin are more sensitive to leptin,
      suggesting that NPY may normally have a tonic inhibitory action on leptin
      mediated satiety signals. NPY-null mice display the normal voracious feeding
      response to injected NPY. Thus, the only condition where we have observed a role
      for NPY in body-weight regulation is in the context of complete leptin deficiency
      -where absence of NPY is beneficial. The activity and general behavior of NPY
      null mice are normal. They appear to have normal spatial and contextual learning
      ability; however, they manifest more anxiety under some conditions. NPY-null mice
      occasionally display spontaneous, seizure-like events. They also are less able to
      terminate seizures induced by GABA receptor antagonists or glutamate receptor
      agonists. These observations are consistent with previous data suggesting that
      NPY plays an important role in dampening excitotoxicity.

PMID- 9769709
TI  - Genetics of type II diabetes.
AB  - Defining the genetic basis of Type II or non-insulin dependent diabetes mellitus
      (NIDDM) will accelerate our progress toward understanding its etiology and will
      provide new therapeutic targets for treatment of this common disease. Here we
      present a brief overview of the history of the search for diabetes genes and
      report current strategies employed by our laboratory and by others in this
      effort. Isolation and subsequent mapping of candidate genes involved in insulin
      production and action has been a major effort in this field. Our lab has focused
      on pancreatic islet beta-cell genes, since the insulin lack of NIDDM is often the
      result of resistance to the action of insulin that is superimposed on a limited
      ability to produce insulin. A number of islet genes have been evaluated,
      including those involved in glucose metabolism, islet K+ channel genes, and
      transcription factors. For each gene, human cDNAs and genomic clones have been
      isolated and simple sequence repeat polymorphisms (SSRPs) identified. The SSRPs
      were used to map the genes by linkage in CEPH pedigrees, or sequence-tagged sites
      (STSs) were used to map the genes to radiation hybrids (RH) or to YAC clones
      containing SSRPs. The SSRPs have then been used as markers for linkage analyses
      in families with NIDDM. Mutation screening by single-strand conformational
      polymorphism analysis and by sequencing has revealed variants that have been
      tested in association studies. A strategy was devised to generate novel expressed
      sequence tags (ESTs) from human pancreatic islet genes by differential display of
      islet mRNA. In the first phase of this project we identified 42 cDNAs that were
      preferentially expressed in pancreatic islets relative to exocrine tissue. When
      compared to sequences in GenBank, novel genes were represented by 69%. Enhanced
      islet expression was confirmed by Northern analysis of RNA. Sequence-tagged sites
      were synthesized for a number of islet ESTs and used to map these genes to human
      chromosomes. This strategy provides an effective means to selectively identify
      and map genes transcribed in human pancreatic islets and to identify novel islet
      candidate genes for NIDDM. Positional cloning of NIDDM genes in families of
      various racial groups is being conducted by a number of labs. Although regions of
      genetic susceptibility are being identified, finding the genes within these
      regions will be difficult because of the polygenic nature of the disease As an
      alternative strategy, we have begun to map genes responsible for monogenic
      disorders of carbohydrate metabolism. Familial hyperinsulinism (HI, OMIM #256450)
      is a rare recessive disease associated with neonatal hyperinsulinism and life
      threatening hypoglycemia. To determine the molecular basis for HI, we mapped the
      gene in multiplex families to chromosome 11p14-15.1. A candidate gene, the
      sulfonylurea receptor (SUR1), was mapped to the region and shown to harbor
      mutations in HI patients. Analysis of 21 identified mutations has revealed the
      role of SUR1 as a nucleotide regulator of the islet ATP-sensitive K+ channel. The
      challenge for the future will be to utilize the information provided by the Human
      Genome Project (i.e., the complete nucleotide sequence and expression maps of the
      genome) to find diabetes-predisposing genes. Our immediate goals include
      collecting families with NIDDM for phenotyping and for DNA analysis and
      continuing to identify suitable candidate genes to be studied in these families.

PMID- 9769710
TI  - Phenotype and genotype in polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a common disorder in premenopausal women and
      is characterized by hyperandrogenic chronic anovulation. The cause is unknown.
      PCOS is associated with significant insulin resistance as well as with defects in
      insulin secretion. These abnormalities place these women at substantial risk for
      developing type 2 diabetes mellitus. A defect in insulin-mediated receptor
      autophosphorylation has been found in a substantial proportion of PCOS women.
      Both PCOS and the insulin resistance that accompanies it appear to have major
      genetic components. Family studies of PCOS have supported this, although they
      suffer from incomplete phenotyping of probands and first-degree relatives. The
      phenotype in males and nonreproductive age females is uncertain. Despite the
      shortcomings of the family studies of PCOS, they have consistently indicated
      familial clustering and suggested that the mode of inheritance is dominant. Our
      initial studies of 50 families of PCOS probands indicate that 24% of sisters are
      affected with PCOS. There also appears to be an intermediate phenotype of sisters
      with regular menstrual cycles who are hyperandrogenic per se (22% of sisters).
      Additionally, there appears to be a major familial defect, with 50% of first
      degree relatives having glucose intolerance (impaired glucose tolerance by oral
      glucose tolerance test or type 2 diabetes mellitus). These findings suggest that
      hyperandrogenism in females and glucose intolerance may be genetic traits in PCOS
      kindreds. Systematic phenotyping will allow assignment of affected status for
      eventual linkage analysis.

PMID- 9769711
TI  - The calcium-sensing receptor (CaR) permits Ca2+ to function as a versatile
      extracellular first messenger.
AB  - The ability of parathyroid cells to recognize and respond to (i.e., "sense")
      small changes in the extracellular Ca2+ concentration (Ca2+o) plays a crucial
      role in mineral ion homeostasis. Expression cloning in Xenopus laevis oocytes
      enabled isolation of a cDNA coding for the bovine parathyroid CaR. CaRs were
      later isolated from human parathyroid and kidney, rat kidney, brain and C-cell,
      rabbit kidney, and chicken parathyroid. All are tissue and species homologs of
      the same ancestral gene. The predicted CaR protein has a large extracellular
      amino-terminus, which binds polycationic CaR agonists; a central core with seven
      membrane-spanning helices, documenting that it is a G protein-coupled receptor;
      and an approximately 200 amino acid carboxyl-terminal tail. The CaR is highly
      expressed in parathyroid and C-cells, along almost the entire nephron and
      gastrointestinal (GI) tract and within numerous regions of the brain,
      particularly hippocampus, cerebellum, and hypothalamus. The CaR's physiological
      importance has been documented by the identification of hyper- and hypocalcemic
      syndromes due to inactivating or activating CaR mutations, respectively. Familial
      hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT)
      are caused by loss-of-function CaR mutations producing Ca2+o "resistance," while
      autosomal dominant hypocalcemia is the result of activating mutations rendering
      CaRs overly sensitive to Ca2+o. In addition to showing altered parathyroid
      responsiveness to Ca2+o, patients with FHH reabsorb too much urinary Ca2+ and
      Mg2+ at a given Ca2+o, while those with autosomal dominant hypocalcemia excrete
      too much, illustrating the CaR's key role in renal handling of divalent cations.
      Recent in vitro data suggest that the CaR directly regulates renal water handling
      in the collecting duct. Indeed, patients with FHH concentrate their urine
      normally, despite their hypercalcemia, while those with autosomal dominant
      hypocalcemia can exhibit impaired urinary concentration at normal or even low
      Ca2+o, suggesting that the CaR enables coordination of renal calcium and water
      handling. In addition to serving these "homeostatic" roles, the CaR likely also
      enables Ca2+o to serve additional roles as an extracellular messenger. The
      receptor regulates key Ca2+ and K(+)-permeable ion channels in hippocampal and
      other brain cells and likely senses local changes in Ca2+o within the brain
      microenvironment accompanying neuronal activation. It is also present in and
      regulates ion channels in lens epithelial cells, potentially playing some role in
      cataract development in hypoparathyroid patients. In keratinocytes and epithelial
      cells of the gastrointestinal tract, in contrast, the CaR may regulate cellular
      proliferation and differentiation, processes known to be modulated by Ca2+o in
      these cell types. Thus, in addition to sensing and regulating systemic Ca2+o, the
      CaR likely enables Ca2+o to act as a local signal for cells within specific
      microenvironments, such as the brain or eye.

PMID- 9769712
TI  - Functional analysis of the PTH/PTHrP network of ligands and receptors.
AB  - Parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) are two
      related proteins that activate a common PTH/PTHrP receptor, yet have quite
      distinct physiologic missions. PTH is the major peptide regulator of blood
      calcium in higher vertebrates, while PTHrP predominantly acts as a paracrine
      regulator of differentiation and local intercellular signaling. To analyze the
      physiological roles of PTHrP and the PTH/PTHrP receptor, "knockout" mice missing
      either the PTHrP or the PTH/PTHrP receptor gene were developed. Both the PTHrP (
      /-) mice and the PTH/PTHrP receptor (-/-) mice exhibit a growth plate
      chondrodysplasia that reflects accelerated differentiation of proliferating
      chondrocytes. Growth plate chondrocytes regulate the local production of PTHrP by
      secreting the protein, Indian hedgehog (Ihh), as they are leaving the
      proliferative pool. Ihh stimulates the production of PTHrP, which then slows the
      differentiation of chondrocytes, thereby delaying the production of Ihh. PTHrP
      also stimulates transport of calcium across the placenta. PTHrP (-/-) mice lack
      the normal elevation of fetal blood calcium (when compared to maternal levels)
      and have low placental transport of calcium. Fragments of PTHrP that do not bind
      to the PTH/PTHrP receptor can correct the defect of placental calcium transport
      in these mice. Thus, this action of PTHrP is not mediated by the PTH/PTHrP
      receptor. The "knockout" mice thus help delineate the roles of PTH. PTHrP, and
      the PTH/PTHrP receptor in an interacting network of ligands and receptors.

PMID- 9769713
TI  - Parathyroid hormone-related protein in the pancreatic islet and the
      cardiovascular system.
AB  - Parathyroid hormone-related protein was discovered as the causative agent
      responsible for the common paraneoplastic syndrome, humoral hypercalcemia of
      malignancy. It is now clear that the PTHrP gene is expressed in virtually every
      cell and tissue in the body at some point in development or adult life and that
      the peptide is critical for normal life. Two of the tissues that produce PTHrP
      are the insulin-producing beta cells of the pancreatic islet and the vascular
      smooth muscle cells of the arterial wall. In this review, the physiologic roles
      of PTHrP in the islet and in the arterial wall are explored. PTHrP is a classical
      neuroendocrine prohormone that undergoes extensive post-translational processing
      to yield a family of daughter peptides that are the mature secretory forms of the
      peptide. In addition to its ability to act as a traditional endocrine, paracrine,
      or autocrine factor, PTHrP appears to be able to act as an "intracrine" factor as
      well, directly entering the nucleus after translation and stimulating
      proliferation, apoptosis, and perhaps other cellular responses as well. The cell
      biology underlying this phenomenon is also explored herein.

PMID- 9769714
TI  - Molecular cloning of (25-OH D)-1 alpha-hydroxylase: an approach to the
      understanding of vitamin D pseudo-deficiency.
AB  - Pseudovitamin D-deficiency rickets (PDDR) is the first identified inborn error of
      vitamin D metabolism. Its clinical course is similar to that of nutritional
      rickets due to simple vitamin D deficiency. The treatment of choice is
      replacement therapy with calcitriol [1,25(OH)2D3]. PDDR is inherited as a simple
      autosomal recessive trait. The PDDR locus has been mapped to chromosome 12q13
      q14. The molecular defect underlying the 25-hydroxyvitamin D-1 alpha-hydroxylase
      enzyme dysfunction has remained elusive due to the lack of sequence information
      for the gene encoding the cytochrome P450 moiety of the enzyme. We have used a
      probe derived from the rat 25-hydroxyvitamin D-24-hydroxylase sequence to
      identify and clone the 1 alpha-OHase cDNA. The candidate gene was transiently
      expressed in P19 embryonal carcinoma cells. Only those cells that were
      transfected with the candidate cDNA in the sense orientation were able to produce
      a compound that co-eluted with the 1 alpha, 25 vitamin D3 standard. Mass
      spectrometry analysis confirmed the identity of the produced metabolite. A human
      genomic clone was isolated from a chromosome 12 cosmid library and subsequently
      mapped to human chromosome 12q13.1-q13.3. To address the putative biological
      function of 24,25-dihydroxyvitamin I) 24,25(OH)2D, we also engineered a null
      mutation in the 24-OHase gene in embryonic stem cells (ES). Animals heterozygous
      for the engineered mutation are normal and fertile. One half of the homozygous
      animals die before weaning. Breeding of surviving females gives an F2 generation
      in which bone development is abnormal at sites of intramembranous ossification.
      Growthplate maturation and endochondral ossification appeared to proceed
      normally. The results show that a complete absence of vitamin D metabolites
      hydroxylated in position 24 during embryogenesis leads to abnormal bone structure
      and suggests a key role for 24,25(OH)2D in the developmental regulation of
      intramembranous ossification.

PMID- 9769715
TI  - Mechanisms of thyroid hormone action: insights from X-ray crystallographic and
      functional studies.
AB  - This review summarizes the studies conducted in our laboratory on the mechanisms
      of thyroid hormone action over the past two decades. We have attempted to place
      our studies on thyroid hormone receptors (TRs) in perspective with the work
      conducted by other investigators that established their nuclear localization, DNA
      binding properties, DNA response elements, and the role of other proteins
      involved in TR-mediated regulation of gene transcription. Recently, our
      crystallographic studies of the TR ligand binding domain (LBD) revealed that the
      ligand has a structural role in the folding of the receptor's hydrophobic core.
      The analysis of the structure led to biochemical and genetic studies that have
      defined the surfaces on the TR LBD required for dimerization and binding of
      coactivator proteins. Placement of the mutations found in patients with the
      syndrome of generalized resistance to thyroid hormone on the TR LBD revealed that
      they were restricted to amino acids in the vicinity of the binding pocket for
      thyroid hormone. The insights gained from the elucidation of the TR LBD structure
      will provide the basis for the design of compounds with selective agonistic or
      antagonistic activities.

PMID- 9769716
TI  - Structural and molecular studies of human chorionic gonadotropin and its
      receptor.
AB  - Human chorionic gonadotropin (hCG) is a placental hormone that stimulates
      secretion of the pregnancy-sustaining steroid progesterone. It and other
      glycoprotein hormones are disulfide-rich heterodimers that share a common alpha
      chain and distinctive beta chains specific to their particular G protein-linked
      receptors. We determined the structure of partially deglycosylated hCG at 2.6 A
      resolution from multiwavelength anomalous diffraction (MAD) measurements of a
      selenomethionyl hCG crystal. We have also begun three- and four-dimensional
      structural studies on the biologically active hormone and have determined the
      structure of the carbohydrate attached to the alpha-subunit. Despite little
      sequence similarity limited to 10% identity, the alpha and beta subunits of hCG
      maintain strikingly similar tertiary folds, with cystine-knot motifs at cores of
      extended hairpin loops. Structural and sequence comparisons indicate an
      evolutionary homology between the glycoprotein hormone chains and other cystine
      knot proteins, notably PDGF, TGF-beta, and NGF. This structural similarity has
      led us to speculate that early hCG secretion has a broader role than solely the
      stimulation of the corpus luteum; indeed, levels of hCG, which rise rapidly in
      the circulation after implantation, are greater than the levels necessary for
      corpus luteum function. One such role of hCG or its subunits could be as a growth
      factor that facilitates endometrial receptivity. Our studies of hCG have also
      identified structural variants, notably in the carbohydrate moiety, that are
      distinctive for patients with a variety of disorders of pregnancy, including
      hydatidiform mole and choriocarcinoma. We have also focused our efforts on using
      information gleaned from the structure of hCG for the design of drug-like
      molecules that might serve as either agonists or antagonists of hCG. To
      facilitate these experiments, we have designed a rapid screen for the
      identification of molecules that might bind the hCG receptor by identifying
      compounds that disrupt binding of hCG to its receptor. This screen employs a
      filamentous phage that displays the extracellular domain of the hCG receptor on
      its surface. Thus far, we have identified a few compounds that disrupt binding of
      hCG with its receptor at a concentration of approximately 1 micromolar. These
      "lead" molecules are currently being modified in an attempt to identify a
      molecule that can disrupt binding of hCG at nanomolar concentrations.

PMID- 9769717
TI  - [Scintigraphy in the early diagnosis of the secondary hypertrophic
      osteoarthropathy syndrome].
AB  - We treated twenty-three patients with secondary hypertrophic osteoarthropathy
      (SHO). Lung cancer was associated with SHO in 21 cases. The underlying conditions
      for the rest of the patients were pulmonary fibrosis, bronchiastasic, pneumonia
      and mediastinal cancer. The history, physical examination, radiography and bone
      scan were performed. For bone-scan it was used intravenously instilled disfonate
      compound marked with 99 mTc-HMDP-"Osteocis" in the dosage of 740 MBq. Mild
      periostosis on the shaft bones was found in 5 patients with positive radio
      labelling. In other patients bone-scan showed polytopic radiolabelling whilst
      radiography didn't show and periostosis. In conclusion we can say that the bone
      scan is very sensitive method for the detection of the increase bone-tissue
      function.

PMID- 9769718
TI  - [Autoantibodies and autoimmune rheumatologic diseases].
AB  - The paper describes the significance of various autoantibodies in autoimmune
      rheumatologic diseases. A greater number of laboratory tests also means a greater
      possibility of diagnosing these diseases. In some cases the antibodies correlate
      with disease activity, some antibodies serve as prognostic indicators, others
      allow the following of disease activity or success of treatment. In any case, the
      role of numerous autoantibodies in the pathogenesis of rheumatologic inflammatory
      diseases is still unclarified und further investigation will be necessary to
      obtain the answer to this important question.

PMID- 9769719
TI  - [Comparative study of the force of flexors and extensors of the cervical spine in
      patients with vertebral syndrome of the cervical spine and in healthy persons].
AB  - This paper deals with the muscle force of the cervical spine in patients with
      cervical syndrome compared to the muscle activity in non-patients. It has thus
      been observed that both the flexors' and the extensors' force of the cervical
      spine is much greater in non-patients (the flexors' P < 0.01 and the extensors' P
      < 0.01). The precise measurements having been carried out by a dynamometer. The
      groups being tested comprised 50 persons each, 25 men and 25 women. The average
      age of the patients group was 43.1 years, namely between 21 and 57 years, while
      that of the non-patients group was 42.3 years, between 24 and 56 years. As
      regards the professional engagement of both groups and, accordingly, the strain
      on the cervical spine and the corresponding musculature, they were approximately
      the same.

PMID- 9769720
TI  - [Work capacity evaluation in patients with ankylosing spondylitis].
AB  - The aim of the study was to establish the employment and working ability for
      patients with ankylosing spondylitis. The study was performed using a
      questionnaire mailed to 185 patients with verified diagnosis of ankylosing
      spondylitis who were treated at the Department of Rheumatology of the University
      Hospital "Sestre milosrdnice" in Zagreb in the last 5 years. The questionnaire
      included a few categories of questions and here we analysed those referring the
      working abilities. The answers were obtained from 92 patients. We took in account
      the data for 79 patients who fall into the age group of working population (men
      to 65 yrs, women to 60 yrs.). In that group there were 50 men and 29 women.
      Twenty-six patients have a full time job, 7 patients have a part-time job, one
      changed the job and 45 of them are retired. The difference of working abilities
      was observed regarding to the physical requirement for the job (P < 0.05) and the
      duration of the disease (P < 0.05). Among the patients who are retired majority
      stated that ankylosing spondylitis was the cause of their retirement. As for the
      patients who still work (N = 34), 14 of them were not on sick-leave the last year
      at all, 2 of them were absent up to one week, 10 patients were absent from 1 to 4
      weeks, 3 patients were on sick-leave from 1 to 3 months, and 5 of them more than
      3 months. Statistically significant difference was observed in sick-leave rate
      regarding to the physical requirements for the job (P < 0.01), but not regarding
      to the duration of the disease (P > 0.05). The results of our study suggest that
      ankylosing spondylitis reduce the working ability especially for patients who
      have a hard job. There is an imperative to maintain the working abilities of
      patients with ankylosing spondylitis as long as possible.

PMID- 9769721
TI  - [Circadian rhythm in hand grip strength in patients with rheumatoid arthritis].
AB  - In 34 inpatients, 22 with diagnosis of rheumatoid arthritis according to revised
      ACR criteria and 12 with diagnosis of other diseases without affection of the
      hands served like control group we measured grip strength in 4 time period during
      the day (7, 11, 15, 19 hours) with the Martin's vigorimeter. Mean grip strength
      value was statistically lower in patients with rheumatoid arthritis in all four
      time periods (P < 0.005). There is general trend of the rising grip strength
      since morning to evening without statistically relevance. Grip strength firmly
      linear negatively correlated with the grade of morning stiffness.

PMID- 9769722
TI  - [The effect of drugs on hand function in rheumatoid arthritis].
AB  - In 30 inpatients with diagnosis of rheumatoid arthritis according ACR criteria we
      evaluated efficacy of non steroid-antiinflammatory drugs (NSAIDs) and
      corticosteroids (CS) on pain, morning stiffness and grip strength. NSAIDs and
      combination of NSAIDs and CS showed statistically significant analgesic effect (P
      < 0.005). Combination of NSAIDs and CS statistically significant shortened
      morning stiffness comparing NSAIDs or CS as single drug. Grip strength didn't
      rise in any investigated group. This could be explained with long disease
      duration (11.69 years). Morning stiffness is symptom not related only to
      extracellular fluid cumulation in affected areas but also to other progressive
      and longlasting disease signs.

PMID- 9769723
TI  - [Clinical features of ankylosing spondylitis--epidemiologic study].
AB  - The aim of the study was to establish some clinical features of ankylosing
      spondylitis in an epidemiological study using a mailed questionnaire. The
      questionnaire was sent to 185 patients with ankylosing spondylitis who were
      treated at the Department for Physical Medicine, Rehabilitation and Rheumatology.
      The answers were obtained from 92 patients (49.7%). In the studied cohort there
      were 60 men and 32 women. The average age of all patients were 51.6 +/- 11.8 yrs.
      In most of the patients (69 or 75%) the duration of ankylosing spondylitis is
      more than 15 years. The diagnosis of ankylosing spondylitis was established on
      average 6.5 years after the beginning of symptoms. Patients suffering from
      ankylosing spondylitis more than 15 years reported that the worst period of the
      disease was the starting 10 years. The main symptoms of the disease are stiffness
      and pain. The aggravation of pain occurs with enhanced physical activity as well
      as with prolonged rest--Painful swelling of one or more joints of 3 weeks
      duration had 63.7%, and more than 3 weeks duration 40.7% patients. There was no
      difference in occurrence of painful swelling extravertebral joints regarding to
      duration of the disease (P > 0.05). The most often affected joints were hips and
      shoulders. Eyes inflammation was reported by 63 patients, and unspecified
      enterocolitis had 16 patients.

PMID- 9769724
TI  - Who pulls the string to pattern cell division in Drosophila?

PMID- 9769725
TI  - The Drosophila genome project: a progress report.

PMID- 9769726
TI  - Survival with HIV infection: good luck or good breeding?

PMID- 9769727
TI  - Stem-cell gene therapy: problems and solutions. The 2nd Conference on Stem Cell
      Gene Therapy: Biology and Technology, Rosario Resort, Orcas Island, WA, USA, 31
      March-2 June 1998.

PMID- 9769728
TI  - The most complex trait of all. Behavior Genetics Association, Stockholm, Sweden,
      8-10 June 1998.

PMID- 9769729
TI  - Innexins: a family of invertebrate gap-junction proteins.

PMID- 9769730
TI  - Changing styles in C. elegans genetics.
AB  - The past 30 years have taken the nematode Caenorhabditis elegans from obscurity,
      as a nondescript member of a large but unglamorous invertebrate phylum, to a
      position as one of the major model organisms. This year, it will acquire a
      particular celeberity as the owner of the first animal genome to be sequenced in
      its entirety. In this review we consider the ways in which genetical
      investigations of this species have begun to change and what some of the
      consequences of the completion of the sequence are likely to be.

PMID- 9769731
TI  - Chimeras and mosaics in mouse mutant analysis.
AB  - As the number of mouse mutants generated by gene targeting continues to grow
      exponentially, the challenge is not how to generate a mutant but how to analyse
      the phenotype. Genes might play multiple roles in development and act in cell
      autonomous and cell non-autonomous modes, making phenotypic analysis complex.
      Genetic mosaic analysis is a powerful tool for dissecting complex gene functions.
      Classical preimplantation chimeras made between mutant and wild-type embryos can
      answer many questions, and new genetic techniques for generating restricted
      genetic mosaicism promise to enhance the future power of mosaic analysis in
      mammals.

PMID- 9769732
TI  - Traps to catch unwary oncogenes.
AB  - The MYC proto-oncogene has long been implicated in the control of normal cell
      growth and its deregulation is associated with the development of neoplasia. The
      MYC protein has a well-established role as a component of signal-transduction
      pathways promoting both proliferation and apoptosis. Because signalling pathways
      that drive cell death and cell proliferation are so tightly coupled, a synergy
      between genetic lesions leading to suppression of cell death and those promoting
      cell proliferation is observed during carcinogenesis. We discuss such synergy
      with respect to the cooperating oncogenes MYC, RAS and BCL2.

PMID- 9769733
TI  - Selfishness and death: raison d'etre of restriction, recombination and
      mitochondria.
AB  - Type II restriction-modification gene complexes, such as the EcoRI system, are
      not easily lost from their host cell. The descendants of cells that lose a
      restriction-modification gene complex are unable to modify a sufficient number of
      recognition sites in their chromosomes to protect them from lethal attack by the
      remaining molecules of restriction enzyme. This capacity to act as a selfish
      genetic element is likely to have contributed to the spread and maintenance of
      restriction-modification systems. Homologous recombination machineries of cells
      and viruses appear to be well adapted to cope with these elements. By
      extrapolation, the capacity of mitochondria to kill their host eukaryotic cell
      might have stabilized their initial symbiosis.

PMID- 9769734
TI  - Lipid peroxidation intensity and lipid status parameters in the estimation of the
      severity of ischemic heart disease.
AB  - Atherosclerotic changes on the coronary arteries are the basis of the ischemic
      heart disease. It is assumed that the initial changes in this process occur as a
      consequence of the lipid peroxidation in the vessel wall. We estimated this
      process through the level of malondialdehyde (MDA) in the serum of 86 patients in
      whom selective coronary angiography was done for the suspected ischemic heart
      disease. According to the number of the stenotic coronary arteries (stenosis
      greater than 50%), we divided the patients into four groups: the control group
      with normal coronary angiography finding, simple, double or triple vessel
      coronary disease. In all the patients we also estimated the other parameters of
      the lipid status (cholesterol, triglycerides, LDL, HDL, Apo-AI, Apo B) and
      atherogenic indices Apo-AI/Apo B, LDL/HDL and HDL/total cholesterol. No
      significant changes were observed in the lipid parameters between the control and
      experimental group. However, mean MDA level in the whole experimental group was
      3.89 mumol/L, 3.93 mumol/L in triple vessel coronary disease, 3.83 mumol/L in
      double vessel and 3.92 mumol/L in single vessel disease group. The difference
      between all the experimental and the control group was highly significant (p <
      0.001). We concluded that the level of MDA--lipid peroxidation index had the
      better correlation with the disease status than the other parameters of lipid
      status and the sensitive atherogenic indices.

PMID- 9769735
TI  - The correlation of cytologic degree of differentiation of infiltrative ductal
      breast carcinoma and cytochemical activity of glucose-6-phosphate dehydrogenase.
AB  - The semiquantitative cytochemical activity of glucose-6-phosphate dehydrogenase
      in imprints of surgical biopsies of 55 patients with invasive ductal breast
      carcinomas was compared to the cytologic degree of differentiation. All
      carcinomas cytologically designated as well differentiated had a low enzyme
      activity. Approximately half of moderately differentiated carcinomas were
      characterized with low score of enzyme activity and only 2 out of 26 poorly
      differentiated tumors had the low enzyme activity. The estimation of cytochemical
      activity of this enzyme may be valuable as the morphologic parameter for
      cytologic evaluation of malignant cells.

PMID- 9769736
TI  - [Primary neurosurgical treatment of craniocerebral war injuries].
AB  - From September 1991 to December 1992, 41 patients with nonpenetrating and 84
      patients with penetrating craniocerebral injuries were neurosurgically treated at
      the Military Medical Academy. The severity of injuries was estimated according to
      GCS and the outcome according to GOS. In 17 out of 27 patients with moderate
      nonpenetrating CCI, the outcome was favorable, and 5 patients out of 7 with
      severe CCI died (p < 0.01). Out of 33 patients with moderate penetrating CCI,
      favorable outcome or moderate disability were observed in 21 patients, and out of
      26 patients with severe CCI, 19 died (p < 0.01). The majority of unilobar CCI
      resulted in favorable outcome or moderate disability, while 10 out of 26 patients
      with multilobar CCI, as well as 9 out of 16 patients with bichemispheric CCI died
      (p < 0.01). Mortality rate in patients with penetrating CCI was 25%. No
      significant differences were observed in the outcome of penetrating CCI in
      relation to the missile type (p > 0.05). Nonpenetrating CCI had a better outcome
      than the penetrating ones (p < 0.05). The outcome of war nonpenetrating CCI
      depended on the severity of injury and of penetrating CCI on the severity injury,
      of the extent of cerebral lesion and the form of penetration, respectively.

PMID- 9769737
TI  - [Alloarthroplasty of war injuries of the elbow joint].
AB  - War injuries require specific approach in order to be optimally managed. In case
      of penetrating or explosive joint injuries, the management should be done with
      regard of the war surgery doctrine. Besides, it is very hard to prognose the
      disability degree after the completed treatment. If we point out that the average
      age of our patients with implanted elbow endoprosthesis was between 23 to 35
      years, our efforts to reduce the disability are understandable. For all the
      reasons cited above, in the last two years we started with the total elbow
      arthroplasty. In all the patients with implanted elbow endoprosthesis, the
      improvement in the amplitude of elbow movements was observed. In 20% cases the
      pain was significantly decreased, and in 80% cases, the elbow became painless.

PMID- 9769738
TI  - [The role of day care hospitals in psychosocial rehabilitation of patients with
      psychiatric war injuries].
AB  - The integrative therapy with the aim of psychosocial rehabilitation of the
      patients with war psychotraumas, treated in the Day-time hospital in the period
      1992-1996, was described and analysed in this study. There were 209 patients (175
      males and 34 females)--133 (63.6%) war veterans and 76 (36.4%) refugees. All
      patients had posttraumatic mental disorders caused by strong war stressors.
      Diagnostic estimation was carried out in accordance with DSM-III-R classification
      and standardized PTSD interview. The most frequent were adaptation disorders and
      posttraumatic stress disorder. Eclectically oriented therapy which consisted of
      pharmacotherapy, psychotherapy, sociotherapy, occupational and recreational
      therapy was applied. The results of therapy and specially group therapy and
      social support, were positive; 182 (67.1%) patients were pronounced capable and
      27 (12.9%) uncapable for work, but in almost all of them the social functioning
      and adaptation were improved. It could be said that the Day-time hospital was the
      optimal place for psychosocial rehabilitation of patients with war psychotraumas,
      because hospitalization and stigmatisation was omitted, with favourable
      conditions for keeping and renewal of the social network.

PMID- 9769739
TI  - [Hemodynamic significance of fluoroscopic diagnosis of coronary artery
      calcification].
AB  - The onset of coronary arterial calcification is an active, organized,
      metabolically regulated process that occurs only when the initial changes of
      atherosclerosis are present. Coronary arterial calcification may represent an
      attempt to protect the arterial wall mechanically. Determination of hemodynamic
      significance in detecting coronary heart disease was the aim of the study. 110
      patients with suspected angina pectoris were performed fluoroscopy and coronary
      angiography after-wards. In 77 patients (70%) was determined coronary
      arteriosclerosis using coronary angiography, and in 33 (30%), finding was normal.
      Out of 77 (70%) patients with positive funding in 44 patients (57.14%)
      calcifications were detect using fluoroscopy, while in 33 (42.86%) were not. Out
      of 33 (30%) patients without arteriosclerosis calcifications were detected in 5
      (15.15%) patients, and in 28 (84.85%) were not. According to our results and
      literature review, the calcification finding confirms the presence of already
      existing significant stenosis on the coronary artery or a high risk for
      hemodynamic disorder within the next two to five years.

PMID- 9769740
TI  - [Evaluation of the level of depression and dementia in patients with primary
      chronic active epilepsy using the Dementia Mood Assessment Scale].
AB  - The study included 40 patients, aged 18-40 years with primary chronic active
      epilepsy, tested by clinical DMAS scale. We have found that the level of
      intelectual function damage (dementia) and mood (depression) rates depended on
      the long duration of epilepsy and the frequency of seizures, less on the
      frequency of specific EEG findings. Types of epileptic seizures and polytherapy
      influenced the depression and dementia rates the least in previous epilepsu
      treatment.

PMID- 9769741
TI  - [Prevalence of risk factors for cardiovascular diseases in aged persons].
AB  - The prevalence study comprised randomly selected sample of 131 females and 109
      males aged 70 years and over in the urban area of Kragujevac community. The
      purpose of this study was to assess the prevalence of cardiovascular diseases, as
      well as the prevalence of factors important for the onset of cardiovascular
      diseases. Ischaemic heart disease was found in 36.6% of females, and in 25.7% of
      males. Six patients (two males--1.8% and five females--3.1% were with
      cerebrovascular disorders. The majority of the participants in the study (70.6%
      of males and 80.9% of females) were hypertensive. The mean value of systolic
      blood pressure was 166.2 mmHg, and the mean value of diastolic blood pressure was
      93.3 mmHg. The mean values systolic and diastolic blood pressure values, serum
      level of total cholesterol, high density and low density cholesterol and glucose
      were relatively high and higher in women than in men. Serum triglycerides were
      the same for both sexes--1.5 mmol/l. The majority of patients included in the
      study had normal body mass index and frequently were the low-fat diet and
      physically active. Only 13.2% were active smokers. It could be concluded that
      some of main risk factors for cardiovascular diseases were not frequent in this
      population of the elderly.

PMID- 9769742
TI  - [Use of domestically produced corn starch in the manufacture of calcium carbonate
      tablets].
AB  - The results of the testing of calcium carbonate tablets, compounded with starch
      as the binding and decay substance are presented. The content of calcium
      carbonate in the tablets, as well as the mass varying, solidity, prodigality and
      aptness to decay were determined. The best properties were observed in the
      tablets with 15% starch mucilage, added suddenly, in the whole amount, to the
      prepared mixture of calcium carbonate and lactose. This procedure is fast and
      simple, and compound tablets of calcium carbonate are of regulated quality.

PMID- 9769743
TI  - [Importance of animal experimental models in psychiatry].

PMID- 9769744
TI  - [Beta blockers and ischemic cerebral disease].

PMID- 9769745
TI  - [Carotid-cavernous fistula with spontaneous remission].
AB  - Carotid-cavernous fistulas (CCF) represent the complication of traumatic injuries
      mostly of bone structures of skull base and face, and rarely of soft neck tissues
      with the fast development of the shunt and imperiled hemodynamics that in a short
      time endangers the patient for the increase of intracranial mass. The therapy of
      this clinical entity significantly changed in the last few years. In this report,
      we present the case of spontaneous CCF healing with the complete restitution of
      neurological deficit and CCF healing in control angiographies.

PMID- 9769746
TI  - [Antiphospholipid antibodies in a female patient with the Sneddon syndrome].
AB  - Sneddon was the first one to describe the association of cerebrovascular insult
      (CVI) and skin changes by livedo reticularis type. Angiography of this patient
      revealed normal brain blood vessels, occlusive changes or the changes similar to
      those in moya-moya disease. Computed tomography (CT) of the brain most frequently
      revealed ischemic lesions and/or diffuse atrophy of the brain, although the
      normal finding was also possible. Considering the frequent finding of the
      increased titer of anticardiolipin antibodies (ACA) in those patients, those
      antibodies could be the most important in the pathogenesis of Sneddon's syndrome.
      A case of female patient, aged 66 years, with livedo reticularis and recurrent
      CVI was presented in this study. By panangiography were revealed normal blood
      vessels of the brain, by scintigraphy two ischemic lesions and by CT ischemic
      lesions with pronounced cortical and subcortical reductive changes. In laboratory
      findings were observed increased immunocomplexes and the presence of lupus-like
      anticoagulants, increased ACA titer, the increase in fibrinogen value associated
      with increased ESR. The result of bone marrow examination was normal, while the
      borreliosis test was negative. Vasculitis was excluded by skin biopsy. Solid
      improvement was noticed after the immunosuppresive therapy was administered, but
      in the last disease exacerbation with new CVI, the outcome was lethal 3 years
      since the disease onset.

PMID- 9769747
TI  - [Anesthesia in Serbia at the end of the 19th and the beginning of the 20th
      century].

PMID- 9769748
TI  - Whither tuition fees?

PMID- 9769749
TI  - Health status in the Caribbean. Has the faculty of medical sciences made a
      difference?
AB  - The Faculty of Medical Sciences has contributed to improvements in health status
      in the Caribbean through its research, training, and service and outreach
      programmes. Basic and applied research has yielded important scientific data and
      information that has guided health care, resulting in decreases in morbidity and
      mortality. Physicians graduating from its undergraduate programme and
      successfully completing its graduate programmes, and nurses and other
      professionals trained in the Faculty, are widely dispersed throughout the
      Caribbean and, together with Faculty staff members, have collaborated with others
      to formulate and implement health policies, and to provide the facilities for
      health education and promotion, and for the care of ill patients. Outreach
      programmes include organising and/or participating in projects, conferences,
      workshops or consultations for or with countries or organisations. Collaboration
      and partnership for all of these activities have been important. The problems and
      challenges are discussed, with an outline of some of the plans being employed to
      resolve them.

PMID- 9769750
TI  - Development of the Faculty of Medical Sciences. Trinidad & Tobago.

PMID- 9769751
TI  - Salmonellosis in Trinidad: evidence for transovarian transmission of Salmonella
      in farm eggs.
AB  - The aim of this study was to determine whether the contents of farm eggs in
      Trinidad are contaminated with Salmonella and if transovarian transmission
      occurs. 750 fresh eggs from 10 farms supplying 75% of the country's eggs were
      cultured for Salmonella. Salmonella was found on the egg shells' surfaces from
      all farms, and in the egg contents from three farms. Isolates were obtained from
      the cultures of the contents and shells of nine (1.2%) and 35 (4.66%) eggs,
      respectively (p < 0.005). Serotypes found in the contents were S. enteritidis
      (0.8%; deduced to be contaminated by transovarian transmission) and S.
      typhimurium (0.4%); those isolated from the shells (contaminated by faecal
      transmission) were S. typhimurium (3.06%), S. enteritidis (0.67%), S. ohio
      (0.27%), S. cerro (0.27%), S. infantis (0.27%) and S. heidelberg (0.13%). This
      study provides the first evidence for Salmonella and, more importantly, S.
      enteritidis, in eggs in Trinidad. This is of major public health significance
      because S. enteritidis infected eggs appear normal and the organism is difficult
      to detect and control. The consumption of these eggs may increase the risk of
      Salmonella infection. Food safety practices, particularly the thorough cooking (>
      or = 70 degrees C) of all egg dishes and the refrigeration (< 10 degrees C) of
      shell eggs and egg dishes, are recommended.

PMID- 9769752
TI  - Renal replacement by regular haemodialysis therapy and renal transplantation in
      Barbados: 1979 to 1997.
AB  - We have reviewed our delivery of highly sophisticated medical therapy,
      haemodialysis and renal transplantation in a Caribbean setting. The purpose has
      been to reflect local outcomes in relation to mortality and survival, but
      comparisons with a vastly larger database have been attempted. Such comparisons
      are extremely difficult due to methodological differences and the fact that
      facilities contributing to that database vary considerably with regard to patient
      age, gender, ethnicity and comorbidity. Nonetheless, the crude data available
      provide important justification for the existence of regular haemodialysis and
      its adjunctive therapy of renal transplantation in the Caribbean.

PMID- 9769753
TI  - Headaches in persons attending polyclinics in Barbados.
AB  - Headache is a very common problem in the community, but only a small proportion
      of people who have it presents to the health services. In the Caribbean little is
      known of its prevalence, the resulting morbidity or the nature of self care used.
      This paper reports on a survey of 679 adults who attended three polyclinics as
      patients, or accompanying young, elderly or acutely ill relatives. 68.9% reported
      having experienced a headache in the previous month. Headaches were more
      prevalent among respondents aged 25-44 years (78.6%) than among those in other
      age groups; in women (73%) than in men; in those living in households of four or
      more people (72%) than in those living in smaller households; in those whose
      family members were reported as using alcohol, tobacco or marijuana singly or in
      combination (70-72.5%) compared to those whose families did not use any of these
      substances (55%); and in those whose family members were reported as having
      allergy, asthma and migraine (72.5 to 77.1%). No significant association was
      shown in relation to employment. 18.4% of the respondents visited the doctor for
      their headache. In the clinical evaluation of these patient, the number of costly
      investigations may be reduced by attention to the epidemiological variables such
      as age and gender, domestic factors such as stress, and family diseases such as
      migraine, asthma and allergy.

PMID- 9769754
TI  - Knowledge and fears of anaesthesia and surgery. The Jamaican perspective.
AB  - This study was undertaken to assess patients' knowledge and perceptions, fears
      and concerns regarding perioperative management. 300 patients were interviewed
      consecutively and a questionnaire was completed for each patient. 25% admitted to
      having anxiety about their upcoming operation. The prevalence of preoperative
      fear was significantly higher in younger patients (age < 40 years, p < 0.05) and
      in more educated patients (secondary and tertiary levels, p < 0.001). The
      commonest fears were those of a morbid nature (e.g. death on the operating
      table). 34% of the patients did not realize that anaesthetists were qualified
      doctors, and only 10% recognized the central role played by anaesthetists in the
      monitoring of vital signs throughout an operation. There is continuing need for
      public education on the role of the anaesthetists in health care, and
      anaesthetists must ensure that preoperative concerns of their patients are
      adequately addressed.

PMID- 9769755
TI  - Orbital psuedotumour with intracranial extension. A case report.
AB  - Inflammatory pseudotumour of the orbit is an unusual condition of unknown
      aetiology which rarely extends beyond the orbit. To our knowledge 19 cases with
      intracranial extension have been reported, none of which involved the pituitary
      fossa or sphenoid sinus. Most required cytotoxic agents, surgery or radiotherapy
      in addition to corticosteroids. We present a case of orbital pseudotumour with
      extension into the pituitary fossa, sphenoid sinus and cavernous sinuses with
      vascular compression. Marked clinical improvement occurred on steroid therapy
      alone.

PMID- 9769756
TI  - Anteriomesenteric duodenal compression syndrome.
AB  - We report the case of a 48 year old man who presented with a 4 month history of
      vomiting and weight loss. Barium studies and upper gastrointestinal endoscopy
      demonstrated anteriomesenteric duodenal occlusion. We discuss the possible
      aetiology and significance of his investigation findings and subsequent
      management.

PMID- 9769757
TI  - Poison centers' perspective.

PMID- 9769758
TI  - FDA study finds test kits effective in spotting birth defects.

PMID- 9769759
TI  - States must be held accountable for new health plans for children.

PMID- 9769760
TI  - New health options available under Medicare + Choice.

PMID- 9769761
TI  - HCFA establishes official website for Medicare information.

PMID- 9769762
TI  - Better surveillance and more awareness needed to deal with rise in antibiotic
      resistance.

PMID- 9769763
TI  - The brain and child development: time for some critical thinking.
AB  - There is widespread interest in the claim that new breakthroughs in neuroscience
      have radical implications for early child care policy. Yet despite parents',
      educators', and policy makers' enthusiasm, there are good reasons to be
      skeptical. The neuroscience cited in the policy arguments is not new, depending
      primarily on three well-established neurobiological findings: rapid postnatal
      synapse formation, critical periods in development, and the effects of enriched
      rearing on brain connectivity in rats. Furthermore, this neuroscience is often
      oversimplified and misinterpreted. While child care advocates are enthusiastic
      about potential applications of brain science, for the most part neuroscientists
      are more cautious and skeptical. After reviewing the evidence and the arguments,
      the author suggests that in the interest of good science and sound policy, more
      of us might adopt a skeptical stance.

PMID- 9769764
TI  - The indoor air we breathe.
AB  - Increasingly recognized as a potential public health problem since the outbreak
      of Legionnaire's disease in Philadelphia in 1976, polluted indoor air has been
      associated with health problems that include asthma, sick building syndrome,
      multiple chemical sensitivity, and hypersensitivity pneumonitis. Symptoms are
      often nonspecific and include headache, eye and throat irritation, chest
      tightness and shortness of breath, and fatigue. Air-borne contaminants include
      commonly used chemicals, vehicular exhaust, microbial organisms, fibrous glass
      particles, and dust. Identified causes include defective building design and
      construction, aging of buildings and their ventilation systems, poor climate
      control, inattention to building maintenance. A major contributory factor is the
      explosion in the use of chemicals in building construction and furnishing
      materials over the past four decades. Organizational issues and psychological
      variables often contribute to the problem and hinder its resolution. This article
      describes the health problems related to poor indoor air quality and offers
      solutions.

PMID- 9769765
TI  - 1% or less: a community-based nutrition campaign.
AB  - OBJECTIVE: The authors evaluated the effectiveness of a community education
      campaign to encourage a switch from high-fat (whole and 2%) milk to low-fat (1%,
      1/2%, and skim) milk as a way to reduce consumption of saturated fat. METHODS:
      Milk sales data were collected from supermarkets in the intervention and
      comparison communities for three one-month time periods: at baseline, immediately
      following the campaign, and six months after the campaign. In addition, trained
      volunteers conducted pre- and post-intervention telephone surveys. RESULTS:
      Overall milk sales increased by 16% in the intervention cities following the
      campaign and remained high at follow-up. Low-fat milk's market share increased
      from 18% of overall milk sales at baseline to 41% of overall milk sales in the
      month following the end of the campaign, an increase in market share that was
      sustained at the six-month follow-up. In the post-intervention telephone survey,
      38.2% of those respondents who reported drinking high-fat milk at baseline
      reported having switched to low-fat milk. CONCLUSION: A focused message
      communicated through paid advertising, public relations activities, and community
      based education programs increased low-fat and overall milk consumption in one
      community.

PMID- 9769767
TI  - Surveillance of injuries.

PMID- 9769766
TI  - Toward more healthful dietary patterns--a matter of policy.

PMID- 9769768
TI  - Mortality due to unintentional injuries in The Netherlands, 1950-1995.
AB  - OBJECTIVE: To detect and explain changing trends in incidence, case fatality
      rates, and mortality for unintentional injuries in the Netherlands for the years
      1950 through 1995. METHODS: Using national registry data, the authors analyzed
      trends in traffic injuries, occupational injuries, and home and leisure injuries.
      RESULTS: Between 1950 and 1970, mortality from unintentional injuries rose,
      reflecting an increasing incidence of injuries. This was followed by a sharp
      decline in mortality due to a decreasing incidence combined with a rapidly
      falling case fatality rate. Starting in the second half of the 1980s, the decline
      in mortality leveled off as the incidence of several injury subclasses once again
      rose. The observed trends reflect several background factors, including economic
      fluctuations (influencing exposure), preventive measures (reducing injury risk
      and injury severity), and improvements in trauma care (lowering the severity
      adjusted case fatality rate). CONCLUSIONS: Injury mortality can be reduced
      through measures that lower injury risk, injury severity, or severity-adjusted
      case fatality rates. Beginning in the mid-1980s, such compensatory mechanisms
      have fallen short in the Netherlands. New policies are needed despite the
      impressive reductions in mortality already reached.

PMID- 9769769
TI  - Effects of Maine's 0.05% legal blood alcohol level for drivers with DWI
      convictions.
AB  - OBJECTIVE: To determine whether a Maine law lowering the legal blood alcohol
      limit (BAL) from 0.10% to 0.05% for people convicted of driving while intoxicated
      (DWI) reduced the involvement of this group in fatal crashes. METHODS: The
      authors calculated changes in the proportions of fatal crashes involving drivers
      with prior DWI convictions from the six-year period before enactment of the law
      to the six-year period following enactment of the law, comparing Maine with the
      other New England states. RESULTS: In Maine, the proportion of fetal crashes
      involving drivers with recorded prior DWI convictions declined 25% following
      passage of the 0.05% DWI law, while the proportion rose in the rest of New
      England during the same years. The proportion of fatal crashes involving drivers
      with recorded prior DWI convictions and illegal alcohol levels also declined
      significantly in Maine, as did the proportion of fatal crashes involving fatally
      injured drivers with recorded prior DWI convictions and illegal alcohol levels.
      Most of the latter decline was due to a decline in alcohol-related fatalities of
      previously convicted drivers with very high BALs, of 0.15% or higher, at the time
      of the fatal crash. Each of these declines in Maine was significant relative to
      the rest of New England. CONCLUSION: Other states should consider instituting
      0.05% BAL limits for convicted DWI offenders.

PMID- 9769770
TI  - State estimates of total medical expenditures attributable to cigarette smoking,
      1993.
AB  - OBJECTIVE: To estimate state-by-state totals of medical expenditures attributable
      to cigarette smoking for calendar year 1993. METHODS: The smoking-attributable
      fractions (SAFs) of total state medical expenditures, by type of expenditure,
      were estimated using a national model that describes the relationship between
      smoking and medical expenditures, controlling for a variety of sociodemographic,
      economic, and behavioral factors. Employing data from the Behavioral Risk Factor
      Surveillance System, the authors used the national model to estimate SAFs for the
      50 states and the District of Columbia, then applied these SAFs to published
      state medical expenditures, by type of expenditures, to estimate total 1993 state
      medical expenditures attributable to smoking. National estimates are the sums of
      state estimates. RESULTS: In 1993, the estimated proportion of total medical
      expenditures attributable to smoking for the U.S. as a whole was 11.8%, with a
      range across states from 6.6% to 14.1%. By type of expenditure, SAFs ranged from
      a low of 8.0% for home health expenditures to a high of 15.9% for nursing home
      expenditures for the nation as a whole. Total U.S. medical expenditures
      attributable to smoking amounted to an estimated $72.7 billion in 1993 (95%
      interval estimate $48.0-$97.4 billion). Estimates of total smoking-attributable
      state medical expenditures (SAEs) ranged from $79.6 million to $8.72 billion.
      CONCLUSIONS: Cigarette smoking accounted for a substantial portion of state and
      national medical expenditures in 1993, with considerable variation among states.
      The range across states was due to differences in smoking prevalence, health
      status, other socioeconomic variables used in the model, and the magnitude and
      patterns of state medical expenditures.

PMID- 9769772
TI  - Credibility of information from official sources on HIV/AIDS transmission.
AB  - OBJECTIVE: The authors analyzed data from the 1991 National Planning Survey to
      (a) assess respondents' awareness of three official sources of information about
      HIV/AIDS (CDC, the Surgeon General, and state health departments); (b) assess
      respondents' perceptions of the reliability of these sources; and (c) compare
      respondents' personal beliefs about HIV transmission with their beliefs regarding
      the experts' view. METHODS: The authors conducted a secondary analysis of the
      responses of the 1622 survey participants who gave complete information. RESULTS:
      People with more years of formal education were more likely to have heard of the
      CDC and the Surgeon General. The CDC was given the highest overall reliability
      rating, followed by the Surgeon General and then state health departments.
      Transmission of HIV/AIDS by various modes of casual contact was perceived more
      likely among those who gave the CDC lower reliability ratings. However,
      regardless of their perceptions of the reliability of the CDC as a source of
      HIV/AIDS information, many respondents believed the probability of transmission
      by casual contact more likely than they believed experts said it was.
      CONCLUSIONS: The discrepancy found between what people believe about health risks
      and what they think experts believe has important implications for the design of
      effective health information campaigns and for the design of questionnaire items
      that aim to assess people's "knowledge" and "attitudes" regarding sensitive
      health topics.

PMID- 9769771
TI  - Residential smoke alarms and fire escape plans.
AB  - OBJECTIVE: To estimate the proportion of U.S. homes with installed smoke alarms,
      smoke alarms on the same floor as occupants' bedrooms, and fire escape plans.
      METHODS: The authors analyzed data on smoke alarm use and fire escape planning
      from a 1994 stratified random telephone survey of 5238 U.S. households. RESULTS:
      Respondents from 91% of surveyed households reported the presence of at least one
      installed smoke alarm, and 94% of respondents reported having an alarm on the
      same level of the home as their sleeping area. The prevalence of installed smoke
      alarms varied by highest education level in the household and income level. Sixty
      percent of all households had designed or discussed a fire escape plan at least
      once; only 17% of these households had actually practiced one. CONCLUSIONS:
      Although overall use of smoke alarms was high, certain population subgroups were
      less likely to have smoke alarms or to have them installed on the same floor as
      bedrooms. Fire escape planning, another important safety measure, was somewhat
      less common, and very few respondents reported having practiced a fire escape
      plan with the members of their household.

PMID- 9769774
TI  - 2nd International Symposium on Malignant Lymphomas. Munich, Germany, September 26
      30, 1998. Abstracts.

PMID- 9769773
TI  - Alice Evans, an early woman scientist at NIH.

PMID- 9769775
TI  - British Society for Rheumatology Heberden Round. Manchester, 10-11 September
      1998. Abstracts.

PMID- 9769776
TI  - [XVIII Forum on Cancer. Paris, France, 2-3 June 1998. Abstracts].

PMID- 9769777
TI  - Cover illustration: case of the month: imaging of early invasive gastric cancer
      with digital radiography using 4 million pixel CCD.

PMID- 9769778
TI  - Cancer genetic counseling and psycho-oncology.

PMID- 9769779
TI  - Cancer chemotherapy in the elderly.
AB  - As the geriatric population is growing, it is increasingly important to be
      familiar with chemotherapy for the elderly. Age-related changes in
      pharmacokinetics are documented for doxorubicin, etoposide, ifosfamide,
      daunorubicin, mitomycin, cisplatin and methotrexate. The hematological toxicity
      of most standard-dose chemotherapy is not affected by age in patients with normal
      organic functions and good performance status, although increased toxicity with
      aging is suggested in the use of actinomycin-D, etoposide, vinblastin,
      methotrexate, methyl-CCNU, doxorubicin and mitomycin, and in dose-intensive
      chemotherapy. Among non-hematological toxicities, only doxorubicin-induced
      cardiomyopathy and bleomycin-induced pulmonary toxicity are demonstrated to be
      accelerated in the elderly. There is no evidence that advanced age decreases the
      efficacy of chemotherapy for tumors, except for Hodgkin's disease and acute
      leukemia. These results suggest that advanced chronological age alone is not
      always associated with severe toxicity and poor prognosis, and that many elderly
      patients with cancer will benefit from chemotherapy. To answer questions
      regarding the optimal chemotherapy regimen, dose and intensity in this
      population, the influence of age should be analyzed in a multivariate approach in
      future studies.

PMID- 9769780
TI  - Prognostic factors and therapeutic options of radiotherapy in pediatric brain
      stem gliomas.
AB  - BACKGROUND: A retrospective analysis was made to clarify the relationship between
      prognosis, radiation dose and survival of brain stem gliomas. METHODS: From 1983
      to 1995, 22 children with brain stem tumors were treated by radiotherapy in the
      Veterans General Hospital-Taipei. Twelve patients had pathology proof and the
      remainder were diagnosed by computerized tomography and/or magnetic resonance
      imaging. Seven patients had postoperative radiotherapy. Fifteen patients had
      radiotherapy as primary management, five of whom had adjuvant chemotherapy. All
      patients received 4000-7060 cGy, either in conventional daily or
      hyperfractionated twice daily radiotherapy. Survival from date of diagnosis was
      calculated by the Kaplan-Meier method. Univariate analyses and multivariate
      analyses were calculated by the log rank test and the Cox proportional hazard
      model, respectively. RESULTS: Most patients showed improvement following
      treatment. The overall 2-year survival rate was 55.5% with a median survival of
      27.1 months. Two-year survival for patients with primary management of operation
      and radiotherapy (n = 7), radiotherapy alone (n = 10) and radiotherapy with
      adjuvant chemotherapy (n = 5) were 66.7, 50 and 53.3%, respectively. In
      univariate analysis, the study revealed that the growth pattern of tumors and the
      simultaneous presence of cranial neuropathy and long tract sign were significant
      prognostic factors (P = 0.017 and 0.036). A trend of better outcome with
      radiation dose > 6600 cGy and the hyperfractionation scheme was also noted in our
      study (P = 0.0573 and 0.0615). However, only the hyperfractionation scheme was
      also noted in our study (P = 0.0573 and 0.0615). However, only the
      hyperfractionation scheme showed significance in multivariate analyses (P =
      0.0355). Survival was not significantly affected by age, gender or method of
      diagnosis. CONCLUSION: Radiotherapy appears to be an effective treatment modality
      of brain stem tumors. Patients with both cranial neuropathy and long tract signs
      had a poorer outcome. Hyperfractionated radiotherapy may give better local
      control and lead to better survival.

PMID- 9769781
TI  - Immunohistochemical detection of tumor cells in the bone marrow of breast cancer
      patients.
AB  - BACKGROUND: Contamination of bone marrow and peripheral blood stem cells with
      tumor cells is a problem that may be encountered when autologous hematopoietic
      stem cell transplantation is conducted concurrently with high-dose chemotherapy.
      METHODS: Using monoclonal antibodies to a variety of tumors, the detection of
      tumor cells in the bone marrow of breast cancer patients was studied by
      immunohistochemistry. RESULTS: KL-1 and CAM5.2 were strongly reactive with breast
      cancer cells, but not with normal bone marrow cells. The reactivity of the tumor
      cells with EMA was not strong, and DF-3 and 115D8 yielded only slightly positive
      reactions. These latter antibodies also exhibited some reactivity to normal bone
      marrow cells. When tumor cells were admixed with normal cells, the sensitivity of
      CAM5.2 and EMA permitted the detection of one cell in 10(4), but with KL-1, the
      detection of one in 10(5) cells was possible. When immunohistochemical staining
      was used in testing 40 patients with advanced or recurrent breast cancer,
      positive reactions were obtained in four of 27 patients (14.8%) with KL-1, four
      of 26 (15.4%) with CAM5.2, and nine of 37 (23.7%) with KL-1 + CAM5.2, figures
      similar to those reported by others who studied stage IV patients. CONCLUSIONS:
      Immunohistochemical staining with KL-1 and CAM5.2 is therefore considered to be a
      useful technique for detecting contamination by tumor cells.

PMID- 9769782
TI  - Establishment of histological criteria for high-risk node-negative breast
      carcinoma for a multi-institutional randomized clinical trial of adjuvant
      therapy. Japan National Surgical Adjuvant Study of Breast Cancer (NSAS-BC)
      Pathology Section.
AB  - BACKGROUND: A multi-institutional randomized clinical trial of adjuvant therapy
      for patients with high-risk node-negative (n0) breast cancer has been undertaken
      in Japan. The pathology panel was organized in order to establish histological
      criteria to identify patient groups with higher rates of recurrence. METHODS:
      Initially, three pathologists independently judged the nuclear grade, composed of
      nuclear atypia and mitotic counts, of 100 n0 invasive ductal carcinomas, focusing
      on interobserver variation of the nuclear grade and its correlation with patient
      prognosis. These pathologists then gave consensus histological types and nuclear
      grades for 130 other n0 breast carcinomas and examined the prognostic
      significance of the grade. RESULTS: In the first study, nuclear grade 2-3
      significantly identified a patient group with a rate of recurrence of 17-20% by
      any pathologists and the degree of agreement for the grade was fair. In the
      second study, the consensus type and nuclear grade identified a group (n = 66)
      with a 22% recurrence rate and another group (n = 64) with a 3.6% recurrence rate
      at 10 years. In 12 tumors, the resection-fixation interval of the tumor did not
      generate any significant difference in mitotic counts. CONCLUSIONS: The
      histological type and the nuclear grade clearly identified a higher-risk patient
      group with n0 breast carcinoma, and may be applied to the multi-institutional
      protocol study when the criteria have been well standardized by the pathologists.

PMID- 9769783
TI  - Lipoid pneumonia in lung cancer: radiographic and pathological features.
AB  - BACKGROUND: Obstructive pneumonia, a synonym for endogenous lipoid pneumonia, is
      often seen in patients with lung cancer, but details of this condition are still
      uncertain. METHODS: To elucidate the features of obstructive pneumonia, we
      radiopathologically studied 147 patients with lung cancer that had been resected.
      RESULTS: Gross inspection of the resected materials revealed evidence of
      endogenous lipoid pneumonia in 33 of the 147 patients with radiography that
      corresponded to obstructive pneumonia. We classified the 33 cases into three
      types as follows: (1) type I lipoid pneumonia, localized to the lung parenchyma
      distal to an airway obstructed by a tumor (23 cases); (2) type II lipoid
      pneumonia, features of type I lipoid pneumonia and consecutively spreading to the
      adjacent segment whose airway was not affected (five cases); (3) type III lipoid
      pneumonia, features of type II lipoid pneumonia and spreading to the isolated
      segments (five cases). Lipoid pneumonia was found in 16 of 89 (18%)
      adenocarcinoma cases and in 17 of 55 (31%) squamous cell carcinoma cases. In type
      I lipoid pneumonia, squamous cell carcinoma cases were predominant over
      adenocarcinoma cases (14 vs nine cases), but in type III lipoid pneumonia,
      adenocarcinoma cases predominated (four vs one case). Further, in cases of type
      III lipoid pneumonia, radiographs frequently revealed that lung cancers were
      cavitated. CONCLUSION: Lipoid pneumonia in lung cancer may be associated with
      factors that play a larger role than the cancer alone. It can be speculated that
      transbronchial dissemination of breakdown products of adenocarcinoma cells,
      including mucin, may contribute to the spread of the non-obstructive component of
      lipoid pneumonia, because the local physical effect of obstructed bronchus does
      not affect the non-obstructive component.

PMID- 9769784
TI  - Efficacy of dose-intensified MEC (methotrexate, epirubicin and cisplatin)
      chemotherapy for advanced urothelial carcinoma: a prospective randomized trial
      comparing MEC and M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin).
      Japanese Urothelial Cancer Research Group.
AB  - BACKGROUND: To evaluate the antitumor activity in patients with T3b, T4 or
      metastatic urothelial carcinoma treated with MEC or M-VAC chemotherapy, by
      performing a multi-center randomized prospective study. METHODS: From 1991 to
      1995, 89 patients with T3b, T4 or metastatic urothelial carcinoma were randomly
      allocated to a methotrexate, epirubicin and cisplatin chemotherapy group (arm 1:
      S-MEC therapy; n = 29), a dose-intensified MEC therapy combined with G-CSF group
      (arm 2: I-MEC therapy; n = 30) or a methotrexate, vinblastine, doxorubicin and
      cisplatin chemotherapy (arm 3: M-VAC therapy; n = 30). At the registration
      center, the patients were stratified into previously untreated patients and
      patients with recurrence after radical operation and then randomly allocated to
      the treatment groups. In each arm, two or more courses of chemotherapy (4-week
      cycles) were performed. RESULTS: Of the 88 eligible patients, four treated with S
      MEC therapy and two treated with I-MEC therapy showed CR. The response rates (CR
      + PR) were 52% (15/29) with S-MEC therapy, 76% (22/29) with I-MEC therapy and 47%
      (14/30) with M-VAC therapy. The response rate with I-MEC therapy was
      significantly higher than that with M-VAC therapy (P = 0.02). Although the
      incidence of leukopenia was low with I-MEC therapy, the incidence of
      thrombocytopenia was high with this therapy. CONCLUSION: MEC therapy used in this
      study is promising in terms of the antitumor effects.

PMID- 9769785
TI  - Unexpected hepatotoxicities in patients with non-Hodgkin's lymphoma treated with
      irinotecan (CPT-11) and etoposide.
AB  - BACKGROUND: Irinotecan (CPT-11) is a topoisomerase I inhibitor that has been
      confirmed to be active against a broad spectrum of neoplasms including non
      Hodgkin's lymphoma (NHL). Because the combination of topoisomerase I and II
      inhibitors seemed to be an attractive therapeutic strategy owing to their
      complementary functions, we conducted a combination phase I study of CPT-11 and
      etoposide, a topoisomerase II inhibitor, in relapsed or refractory non-Hodgkin's
      lymphoma (NHL). METHODS: The starting doses of CPT-11 and etoposide were 30
      mg/m2/day (days 1-3 and 8-10) and 40 mg/m2 (days 1-3), respectively. RESULTS: All
      three patients who received the starting dose developed dose-limiting toxicities
      including one case of grade 4 neutropenia lasting for > 7 days, one of grade 3
      serum transaminase elevation and one of grade 3 hyperbilirubinemia. All three
      patients presented hepatotoxicity > or = grade 2. The starting dose level was
      judged to be the maximum tolerated dose (MTD) and further dose escalation of this
      combination was halted. The patient who developed grade 3 hyperbilirubinemia
      presented a second peak of plasma SN-38, an active metabolite of CPT-11, on the
      concentration-time curve for day 3, suggesting the possibility of the
      enterohepatic circulation of SN-38 and of a drug-to-drug interaction. No durable
      objective response was observed in the three patients treated at the starting
      dose. CONCLUSIONS: We conclude that etoposide is not recommended for combination
      with CPT-11 in NHL patients because of unexpected frequent hepatotoxicities.

PMID- 9769786
TI  - Difficult tracheal intubation in patients with retinoblastoma caused by 13q
      deficiency.
AB  - Anesthetic management of retinoblastoma patients is unremarkable in most cases.
      Patients are most often babies and laryngoscopic procedures for intubation are
      usually easy. However, we recently experienced two cases with retinoblastoma with
      whom tracheal intubation was accomplished with difficulty. We report the two
      cases with a review of all 5-year records of retinoblastoma (rbl) in our
      institution. The cases we experienced recently were all patients with rbl with
      deletion of the long arm of thirteenth chromosome (13q-). In the 5-year review,
      the incidence of the difficult intubation was significantly higher (P < 0.05) in
      rbl with 13q- (4/11) than in rbl without 13q- (0/147). In our experience
      macroglossia was noted for the difficulty in the intubation. We assume that some
      patients with rbl will be cases of difficult intubation even to cannot ventilate
      cannot intubate level when the results of their chromosomal analysis show a
      deletion on the thirteenth chromosome.

PMID- 9769788
TI  - Intracystic papillary carcinoma of the breast in male: case report and review of
      the Japanese literature.
AB  - We report a case of intracystic papillary carcinoma of the breast in a 62-year
      old Japanese man, who came to our hospital complaining of a right subareolar
      mass. Imaging diagnosis was a cyst with an intracystic component. Since repeated
      aspiration biopsy cytology was interpreted as a borderline lesion, no additional
      treatment had been given. Because he wanted the removal of the mass 14 months
      after his first visit, an excisional biopsy was performed under local anesthesia.
      Pathological examination revealed the intracystic component to be non-invasive
      papillary carcinoma. Although the incidence of male breast cancer is
      approximately 1% of all breast cancer, intracystic papillary carcinoma in the
      male is very rare. From a review of the literature on this disease in Japanese
      men, an intracystic component can often be demonstrated by ultrasound. However,
      it is difficult to confirm malignant cells by aspiration biopsy cytology of cyst
      fluid. Since some cases have a local relapse, excisional biopsy and long-term
      follow-up are indicated.

PMID- 9769787
TI  - Well differentiated adult-type fibrosarcoma arising from the occipital
      subcutaneous tissue in a 17-year-old man: case report with immunohistochemical
      study.
AB  - We report a case of a 17-year-old man with a spindle cell tumor in the occipital
      subcutaneous tissue. The enucleated tumor, measuring 2.5 x 2.0 x 1.0 cm, had a
      broad-bean shape and well circumscribed border and was localized to the subcutis
      without dermal involvement. Microscopically, the tumor was composed of uniform
      spindle cells showing interlacing bundle formation and a herringbone pattern. The
      neoplastic cells were separated by collagen fibers in parallel fashion, the
      amount of which varied with different areas in the tumor. Mitotic figures were
      eight mitoses per 50 high-power fields in number. The neoplastic cells were
      positive for vimentin, Factor-XIIIa, alpha-smooth muscle actin and CD34, but
      negative for desmin, calponin, high molecular weight caldesmon, smooth muscle
      myosin heavy chain, collagen type IV, laminin and S-100 protein. These
      immunohistochemical results indicated that the neoplastic cells showed
      differentiation toward fibroblasts/myofibroblasts/dendritic interstitial cells.
      Although more than 50% of the neoplastic cells were positive for CD34, the
      present tumor should be diagnosed as well differentiated fibrosarcoma, adult
      type, rather than extrapleural solitary fibrous tumor and fibrosarcomatous areas
      of dermatofibrosarcoma protuberans, on the basis of routine microscopic findings
      mentioned above.

PMID- 9769789
TI  - Tentative studies in non-small cell lung cancer in Japan and Spain.

PMID- 9769790
TI  - International Society of Pediatric Oncology (SIOP) XXX meeting. Yokohama, Japan,
      October 4-8, 1998. Abstracts.

PMID- 9769791
TI  - The essentials of the complete skin examination.
AB  - The skin is unique among organs in that it is entirely exposed. Complete
      examination is thus possible and, when done well, incorporates input from a
      variety of the senses. A dermatologist's thoughts regarding the essential aspects
      of the complete skin examination are presented.

PMID- 9769792
TI  - Infectious diseases.
AB  - Approximately 5% of the general population develops a skin infection each year,
      leading to a significant number of outpatient visits to the primary care
      physician. Bacteria, infestations, fungi, yeasts, and viruses are organisms that
      present with a myriad of cutaneous findings that pose a challenge to the
      investigating clinician. This article provides a contemporary review of these
      skin infections, with particular emphasis on clinical features, and a concise,
      updated review on therapies.

PMID- 9769793
TI  - Update on cutaneous manifestations of HIV infection.
AB  - The skin is affected in virtually all patients with HIV infection. Many articles
      and several books have been published that deal with these disorders for a number
      of reasons. First, cutaneous disease may serve as the initial or only problem
      that the patient suffers for much of the course of the HIV infection. Second,
      serious opportunistic infections may present for the first time in the skin, so
      that a skin lesion may be a harbinger of the patient's having a life-threatening
      illness. Third, skin disorders in these patients may appear unusual and hence may
      not be accurately diagnosed by clinical inspection alone. Furthermore, response
      to treatment may be poorer than expected. Thus, skin diseases in the HIV-infected
      patient are important and, in some cases, may be the most debilitating element of
      the patient's condition.

PMID- 9769794
TI  - Cutaneous manifestations of sexually transmitted diseases.
AB  - Sexually transmitted diseases remain a prevalent problem in the United States and
      throughout the world, despite efforts in prevention and education. This review
      highlights the cutaneous manifestations of the following sexually transmitted
      diseases: syphilis, chancroid, lymphogranuloma venereum, granuloma inguinale,
      genital herpes, genital warts, scabies, and pediculosis pubis. Emphasis is placed
      on the clinical findings, diagnostic methodology, and recommended treatment for
      each disease.

PMID- 9769795
TI  - Allergic dermatoses.
AB  - Defining "allergy" and elucidating the immunopathology of what is too often
      described as allergic rashes is the objective of this article. The
      differentiation of inflammatory reactions, which at times is indistinguishable
      from the immunologic dermatoses is outlined. A rationale plan for management,
      with indications warranting referral to "the specialist" are suggested.

PMID- 9769796
TI  - Psoriasis.
AB  - Psoriasis is a common skin condition that can be controlled in nearly every
      patient. The diagnosis of psoriasis is generally made on the basis of
      identification of skin lesions of characteristic morphology in characteristic
      locations. A variety of treatments and resources are available to patients with
      psoriasis and to the physicians who treat them. Development of an appropriate
      treatment regimen is facilitated by categorization of psoriasis into localized
      versus generalized forms.

PMID- 9769797
TI  - Acne and rosacea.
AB  - The diagnosis of acne and rosacea are reviewed in this article, and specific
      therapeutic strategies are discussed for these extremely common diseases.

PMID- 9769798
TI  - Hair diseases.
AB  - A few common causes of hair loss account for the vast majority of cases. A well
      directed history and simple physical examination is often sufficient to make a
      diagnosis. Laboratory testing is often unnecessary. A scalp biopsy can be useful,
      but only if processed and interpreted correctly. Androgenetic alopecia, alopecia
      areata, senescent alopecia, telogen effluvium, traction alopecia,
      trichotillomania, and cosmetic hair damage are common causes of non-scarring
      alopecia. Discoid lupus erythematosus, lichen planopilaris, and central,
      centrifugal scarring alopecia are the most common forms of scarring hair loss.

PMID- 9769799
TI  - Nail disorders. Diagnosis and treatment of infectious, inflammatory, and
      neoplastic nail conditions.
AB  - Nail disorders are very common, and about 50% of all nail conditions are of
      fungal etiology. A proper diagnosis is essential because many nail conditions
      look alike. Diagnosis and treatment of other nail disorders, such as psoriasis,
      lichen planus, and neoplasms, are discussed.

PMID- 9769800
TI  - Pigmentary diseases.
AB  - Abnormalities of pigmentation are common and frequently produce great concern in
      patients presenting to primary care physicians. Although many pigmentary changes
      arise as a consequence of inflammatory skin disorders, it is important to
      differentiate a primary skin disease from postinflammatory changes. Early
      recognition of a pigmentary disease allows the clinician to begin appropriate
      therapy at a stage when medical intervention may be more effective. Although many
      skin disorders are mainly of cosmetic concern, the condition may be devastating
      psychologically, requiring the clinician to be sensitive to the overall impact of
      the disorder and treat it accordingly.

PMID- 9769801
TI  - 27th Scandinavian Congress of Rheumatology. Aarhus, Denmark, 5-8 June 1998.
      Abstracts.

PMID- 9769802
TI  - The American Society of Neuroradiology. Neuroradiology research: the
      opportunities and the challenges.
AB  - The next decade will witness an explosion of research and development in the
      neurosciences. The imaging of physiologic and functional processes--the frontier
      today--will become the norm. There are huge populations of patients with
      neurodegenerative and cerebrovascular diseases that require nonanatomic
      diagnostic evaluation. Radiologists must cease being just readers of morphologic
      images. They must broaden their scope and their areas of expertise. Imaging
      guided therapy of all forms will alter the types of interventions we perform on
      patients. These new techniques will increase the efficacy of neuro-interventions
      while decreasing their morbidity and mortality. Resources, both human and
      financial, will be conserved. Radiologists can participate in this wonderful
      future if they broaden their training. Information management and the use of
      imaging for procedural guidance are the bases of our profession, but we are weak
      in the clinical applications of the technology. We must realize that our clinical
      colleagues are poised to assume the leadership in imaging research and
      development and in its performance. The challenge to the leaders of radiology is
      quite apparent: the recognition of the need to train for the future with the most
      open of minds and the least rigidity. This requires that we all understand the
      depth of the merger between the imaging and the clinical sciences that is
      occurring and that will increase substantially in the future. We must be the
      leaders in such a merger; otherwise, we will not be participants.

PMID- 9769803
TI  - The American Society of Head and Neck Radiology. Head and neck imaging: the next
      10 years.
AB  - In the future, we will see continued advancements in all areas of head and neck
      radiology. Because of the rapid pace of developments in the areas of metabolic
      and functional imaging and gene therapy, it is likely that currently unsuspected
      and unknown future applications will also fall within the purview of
      radiologists. It is imperative that our specialty increase our investment in
      areas of investigation that were once believed to be outside the realm of
      imaging. Only then will be able to maintain our participation in
      multidisciplinary investigations that use imaging-based techniques.

PMID- 9769804
TI  - Training issues in neuroradiology and head and neck radiology.

PMID- 9769805
TI  - The Society of Cardiovascular and Interventional Radiology. Future directions in
      vascular and interventional radiology research.

PMID- 9769806
TI  - Diane S. Babcock, MD, and Carol M. Rumack, MD Armed Forces Institute of Pathology
      1998-1999 distinguished scientists.

PMID- 9769807
TI  - A compendium of managed care: past, present, and hints of the future--Part II.

PMID- 9769808
TI  - Gadolinium-enhanced MR angiography of the carotid arteries: a small step, a giant
      leap?

PMID- 9769809
TI  - The case strengthens for allergy to contrast media.

PMID- 9769810
TI  - Helical CT in children: technical considerations and body applications.

PMID- 9769811
TI  - Central nervous system candidiasis in very low-birth-weight premature neonates
      and infants: US characteristics and histopathologic and MR imaging correlates in
      five patients.
AB  - PURPOSE: To analyze the high-resolution (i.e., 5.0- or 7.5-MHz) ultrasonographic
      (US) imaging characteristics of central nervous system (CNS) candidiasis and
      their histopathologic and magnetic resonance (MR) imaging correlates in very low
      birth-weight (VLBW) premature neonates and infants with systemic candidiasis.
      MATERIALS AND METHODS: The US images obtained in one VLBW neonate (age, 24 days;
      weight, 846 g) and four VLBW infants (age range, 36-161 days; weight range, 800
      1, 360 g) with proved CNS candidiasis complicating systemic candidiasis and the
      clinical (n = 5), histopathologic (n = 3), and MR imaging (n = 2) correlates were
      retrospectively reviewed. RESULTS: The cranial US findings consisted of
      parenchymal abnormalities in four and ventricular lesions in three patients. The
      most common findings were multiple echogenic, rim-like microabscesses (four
      patients) scattered in the subcortical, periventricular, and basal ganglial
      areas. Confluent macroabscess formation, seen as echogenic mass-like lesions with
      hypoechoic centers in the periventricular regions and/or thalami, was noted on
      the US images obtained in two patients. The ventricles showed dilatation in two,
      increased ependymal echogenicity in three, the presence of intraventricular
      echogenic septa in two, and a lumpy choroid plexus or the presence of debris in
      two patients. US findings correlated well with MR imaging and autopsy findings.
      The histopathologic changes in the posterior fossa were well demonstrated on MR
      images but not demonstrated on 5.0- or 7.5-MHz US images. CONCLUSION: CNS
      candidiasis in VLBW neonates and infants has characteristic US features that may
      help in the early diagnosis of CNS involvement in systemic candidiasis.

PMID- 9769812
TI  - Normal brain in human newborns: apparent diffusion coefficient and diffusion
      anisotropy measured by using diffusion tensor MR imaging.
AB  - PURPOSE: To establish quantitative standards for the directionally averaged water
      apparent diffusion coefficient (D) and quantitative diffusion anisotropy (A
      sigma) of normal brains in newborns by using diffusion tensor magnetic resonance
      (MR) imaging. MATERIALS AND METHODS: Diffusion tensor MR imaging was performed
      during the first 36 hours of life in 22 newborns (gestational age range, 31-41
      weeks). Values of D and A sigma were measured in regions of interest chosen in
      the cortical gray matter, centrum semiovale, caudate nuclei, lentiform nuclei,
      thalami, internal capsules, and cerebellar hemispheres. RESULTS: The D values in
      the gray and white matter in newborns are considerably higher than those in
      adults. There is a striking correlation between gestational age and D, with D
      decreasing as gestational age increases. The A sigma values in the white matter
      in newborns are lower than those in adults. Values of A sigma show statistically
      significant correlations with gestational age only in the white matter of the
      centrum semiovale, in which A sigma values increase sharply near term.
      CONCLUSION: The D values primarily reflect overall brain water content. The A
      sigma values are more sensitive to tissue microstructure (e.g., white matter
      packing and myelination). The D and A sigma images reveal information and not
      apparent on T1- and T2-weighted images.

PMID- 9769814
TI  - Diagnosis please. Case 3: Renal tuberculosis.

PMID- 9769815
TI  - Focal brain lesions: effect of single-voxel proton MR spectroscopic findings on
      treatment decisions.
AB  - PURPOSE: To determine the influence of single-voxel proton magnetic resonance
      (MR) spectroscopic findings on the treatment of patients suspected of having a
      brain tumor. MATERIALS AND METHODS: Medical records were reviewed in 78 patients
      who underwent MR spectroscopy for evaluation of a focal brain mass suspected of
      being neoplastic. MR spectroscopic findings were positive for neoplasm in 49
      patients and negative in 29. Treatment with or without performance of biopsy was
      noted. In patients with positive findings who underwent irradiation or
      chemotherapy without biopsy and in patients with negative findings who were
      treated medically or followed up for interval changes, MR spectroscopy was
      classified as having a potential positive influence on treatment. In patients
      with positive findings with subsequently proved nonneoplastic lesions and in
      patients with negative findings with subsequently proved tumors, MR spectroscopy
      was classified as having a potential negative influence. RESULTS: MR spectroscopy
      in eight (16%) patients with positive findings and in 15 (52%) patients with
      negative findings had a potential positive influence on treatment. In two (3%)
      patients, MR spectroscopy had a potential negative influence. CONCLUSION: MR
      spectroscopy may play a beneficial role in the management of suspected brain
      tumors. Prospective studies are needed to test the effect of MR spectroscopy on
      clinical practice and to measure costs and benefits.

PMID- 9769816
TI  - Brain injury and neurometabolic abnormalities in systemic lupus erythematosus.
AB  - PURPOSE: To investigate with statistical analysis the relationship between brain
      injury measured with magnetic resonance (MR) imaging and that measured with
      proton (hydrogen-1) MR spectroscopy. MATERIALS AND METHODS: Forty-two patients
      (34 female, eight male; mean age +/- SD, 38.7 years +/- 13.1; age range, 6-60
      years) with systemic lupus erythematosus (SLE) were examined with H-1 MR
      spectroscopy to measure N-acetylaspartate (NAA), creatine (Cr), and choline (Cho)
      levels in normal-appearing white matter and with MR imaging to detect anatomic
      abnormalities. RESULTS: Results of linear regression analysis revealed an
      association between the NAA/Cr ratio and anatomic abnormalities (P = .03).
      However, only small focal lesions were independently related to NAA/Cr ratio
      changes (P = .04). Results of a similar analysis showed associations between the
      Cho/Cr ratio and anatomic abnormalities (P = .002). An elevated Cho/Cr ratio and
      cerebral infarction were independently associated (P = .02), as were a decreased
      Cho/Cr ratio and severe cortical atrophy (P = .02). CONCLUSION: Cerebrovascular
      abnormalities underlie diffuse cerebral injury in SLE, with small vessel injury
      (i.e., small focal lesions) primarily associated with a decreased NAA/Cr ratio
      and medium vessel injury (i.e., infarct) primarily associated with an increased
      Cho/Cr ratio. Statistical integration of H-1 MR spectroscopic and MR imaging
      findings over large data sets provides insights into the relevance of individual
      MR imaging-visible brain abnormalities in SLE. This statistical approach may be
      applicable to other systemic diseases complicated by brain injury.

PMID- 9769817
TI  - Perfusion CT of the brain: diagnostic approach for early detection of ischemic
      stroke.
AB  - PURPOSE: To determine the value of perfusion computed tomography (CT) in a
      clinical study of patients with stroke and compare the results with single photon
      emission CT (SPECT) findings. MATERIALS AND METHODS: Perfusion CT was performed
      within 6 hours of symptom onset in 32 patients with possible stroke. Cerebral
      blood volume (CBV), cerebral blood flow (CBF), and time to peak contrast material
      enhancement were calculated on the basis of the CT results. Cerebral SPECT was
      also performed in a subgroup of 18 patients. Perfusion CT and SPECT findings were
      compared in a lesion-by-lesion analysis. Perfusion CT results were compared with
      follow-up CT and magnetic resonance imaging findings. RESULTS: Areas of reduced
      CBF were detected with the aid of perfusion CT in 25 of 28 patients with a proved
      infarct (sensitivity, 89%). The results of the CBF maps corresponded well to
      SPECT findings in 13 (81%) of 16 patients, but ischemia was located outside the
      scanning level in the other three patients and was therefore missed. Perfusion CT
      revealed various changes in CBF, CBV, and time to peak enhancement in ischemic
      territories. CONCLUSION: Perfusion CT not only allows early detection of cerebral
      ischemia but also yields valuable information about the extent of perfusion
      disturbances.

PMID- 9769818
TI  - Carotid artery stenosis, occlusion, and pseudo-occlusion: first-pass, gadolinium
      enhanced, three-dimensional MR angiography--preliminary study.
AB  - PURPOSE: To determine the accuracy of gadolinium-enhanced three-dimensional
      magnetic resonance (MR) angiography in the evaluation of carotid artery stenosis.
      MATERIALS AND METHODS: A prospective blinded comparison of first-pass MR
      angiography with conventional digital subtraction angiography (DSA) was performed
      in 21 patients suspected of having carotid artery stenosis. MR angiography was
      performed on a 1.5-T magnet with gradient overdrive equipment, with a coronal
      radio-frequency-spoiled, three-dimensional, fast low-angle shot sequence after
      intravenous injection of contrast material. The guidelines of the North America
      Symptomatic Carotid Endarterectomy Trial for measuring stenosis of the internal
      carotid artery were applied on maximum intensity projection images and
      conventional angiograms. RESULTS: Grading of stenoses at MR angiography agreed
      with that at DSA in 92% of the 44 carotid arteries. In the 18 carotid arteries
      with severe stenosis (70%-99%), agreement was 94%. All internal carotid
      occlusions (n = 7) or pseudo-occlusions (n = 3) were accurately detected with MR
      angiography. CONCLUSION: The accuracy of gadolinium-enhanced MR angiography in
      characterizing the degree of carotid stenosis was high. Findings with MR
      angiography were accurate for differentiating between occlusion and pseudo
      occlusion.

PMID- 9769819
TI  - Takayasu arteritis: evaluation of the thoracic aorta with CT angiography.
AB  - PURPOSE: To determine the diagnostic accuracy of computed tomographic (CT)
      angiography in the evaluation of Takayasu arteritis. MATERIALS AND METHODS:
      Twenty-five patients with clinical symptoms suggestive of Takayasu arteritis
      underwent CT angiography and conventional angiography. Takayasu arteritis was
      diagnosed in 20 patients on the basis of conventional angiography. CT angiography
      was performed with a helical CT scanner after injection of a bolus of contrast
      material, and images were generated for three-dimensional display, multiplanar
      reformation, and maximum intensity projection. For vascular assessment, all
      images from CT angiography were used, and the results were compared with those
      from conventional angiography. RESULTS: CT angiography clearly depicted various
      luminal changes, including stenosis, occlusion, dilatation, and aneurysm, in the
      thoracic aorta and its major branches. CT angiography accurately depicted 190
      (95%) of 200 arteries, although the extent of the steno-occlusive lesions was
      overestimated in five (2%) and underestimated in five (2%). Furthermore, CT
      angiography depicted mural changes, including wall thickening, calcification, and
      mural thrombi, not seen with conventional angiography. The sensitivity and
      specificity of CT angiography in the diagnosis of Takayasu arteritis were 95% and
      100%, respectively. CONCLUSION: CT angiography clearly depicts both luminal and
      mural changes in the thoracic aorta and its major branches and has a high
      accuracy in the diagnosis of Takayasu arteritis.

PMID- 9769820
TI  - Aortoiliac aneurysms: endoluminal repair--clinical evidence for a fully supported
      stent-graft.
AB  - PURPOSE: To evaluate aortoiliac aneurysms repaired with endovascular stent-grafts
      complicated by hemodynamically significant graft stenosis. MATERIALS AND METHODS:
      Fifty-four patients (52 men, two women; age range, 41-90 years; mean age, 75
      years) with aneurysms of the infrarenal aorta (n = 36) or iliac artery (n = 18)
      underwent repair by means of placement of an endovascular stent-graft. Technical
      success was evaluated angiographically during and after placement. At follow-up
      (range, 12-44 months), all patients underwent sequential duplex ultrasonography,
      helical computed tomography, and physical examination. RESULTS: Stent-grafts were
      placed successfully in all cases. Stenosis at the internal iliac arterial origin
      was identified at angiography in 17 patients (31%). Supplemental intragraft
      stents were placed in 11 patients, and stent-graft angioplasty alone was
      performed in one patient. Intragraft stents were placed percutaneously in five
      patients when stenosis was discovered during follow-up. CONCLUSION: Supplemental
      intragraft stents were required in 31% of aortoiliac endovascular stent-grafts to
      correct stent-graft stenosis and preserve long-term function. Placement of a
      fully supported stent-graft is necessary to repair an aortoiliac aneurysm.

PMID- 9769821
TI  - Acute colorectal obstruction: stent placement for palliative treatment--results
      of a multicenter study.
AB  - PURPOSE: To evaluate the usefulness of stent implantation as a palliative
      treatment in patients with acute colonic obstruction who are not surgical
      candidates. MATERIALS AND METHODS: Twenty-four patients (eight women, 16 men; age
      range, 60-98 years) with acute colonic obstruction underwent colonic stent
      placement. In nine patients, the procedure was considered a primary palliative
      treatment; seven patients had a previous diagnosis of disseminated neoplastic
      disease, and two were not surgical candidates because of their poor general
      condition. In the remaining 15 patients, stent placement was considered the
      definitive palliative treatment after tumor staging. The mean time of follow-up
      was 8.4 months (range, 1-24 months) for patients who lived and 6.3 months (range,
      1-12 months) for those who died. RESULTS: Stent placement was successful in all
      patients. Clinical and radiographic findings of bowel obstruction resolved within
      24 hours after stent placement in 23 (96%) patients. None of the patients
      required colostomy for bowel decompression after immediate stent placement.
      Complications developed in 10 (42%) patients: Two (8%) patients had mild rectal
      bleeding; three (12%), abdominal pain; two (8%), malpositioning of the stent; two
      (8%), pseudo-obstructive episodes due to fecal impaction; and one (4%), occlusive
      tumor ingrowth into the stent lumen. One (4%) patient underwent surgery to
      resolve stent malfunction due to poor positioning. Two (8.3%) patients--one with
      malpositioning of the prosthesis and the other with stent occlusion--required a
      new stent. The remaining complications required no further treatment. The
      mortality rate at 6 months was 24%. Eight patients were alive at the time this
      article was written. CONCLUSION: Colorectal stent placement resulted in
      successful palliation of acute colonic obstruction in patients with disseminated
      neoplastic disease.

PMID- 9769822
TI  - Extrahepatic arterial supply to the liver: observation with a unified CT and
      angiography system during temporary balloon occlusion of the proper hepatic
      artery.
AB  - PURPOSE: To evaluate routes of potential extrahepatic arterial supply to the
      liver. MATERIALS AND METHODS: Twenty-three patients with liver tumors underwent
      computed tomographic (CT) arteriography of extrahepatic arteries before and after
      temporary balloon occlusion of the proper hepatic artery. The right inferior
      phrenic artery (RIPA), left inferior phrenic artery (LIPA), superior mesenteric
      artery (SMA), celiac axis, and left gastric artery (LGA) were evaluated. RESULTS:
      During temporary balloon occlusion of the proper hepatic artery, extrahepatic
      arterial supply was immediately evident in 22 of 23 patients (96%). The liver was
      supplied by the RIPA in 17 of 20 patients (85%), by the LIPA in five of six
      (83%), by the SMA in eight of 16 (50%), by the celiac axis in two of 10 (20%),
      and by the LGA in one of six (17%). There was no apparent relationship between
      the enhanced zones supplied by extrahepatic arteries and the presence or absence
      of nearby tumors. CONCLUSION: Extrahepatic arterial supply to the liver was
      readily evident in a large proportion of patients during temporary balloon
      occlusion of the proper hepatic artery. This finding suggests a need for
      consideration of extrahepatic arterial supply when angiographic intervention for
      liver tumors is contemplated.

PMID- 9769823
TI  - Hepatic perfusion after liver transplantation: noninvasive measurement with
      dynamic single-section CT.
AB  - PURPOSE: To compare hepatic perfusion values after orthotopic liver
      transplantation with those in healthy volunteers. MATERIALS AND METHODS: Dynamic
      single-section computed tomography (CT) of the liver was performed in 50
      participants, including 30 study patients who had undergone orthotopic liver
      transplantation and had no clinical evidence of postoperative complications (mean
      age, 53.7 years) and 20 healthy volunteers (control subjects) (mean age, 59.0
      years). CT scans were obtained at a single level to include the liver, spleen,
      aorta, and portal vein. Scans were obtained over 88 seconds (one baseline scan
      followed by 16 scans every 2 seconds and, then, eight scans every 7 seconds)
      beginning with the injection of 40 mL of contrast agent (flow rate, 10 mL/sec).
      On each CT scan, the attenuation of these organs was measured in regions of
      interest to provide time-attenuation curves. From these data, the arterial,
      portal venous, and total perfusion of the liver were calculated, and the hepatic
      perfusion index was assessed. RESULTS: In control subjects and study patients,
      respectively, mean arterial hepatic perfusion was 0.16 and 0.25 mL/min/mL (P =
      .001 [two-tailed paired Student t test]), mean portal venous perfusion was 1.22
      and 1.26 mL/min/mL, mean total liver perfusion was 1.38 and 1.50 mL/min/mL
      (difference not significant), and the mean hepatic perfusion index was 0.12 and
      0.16 (P = .002). CONCLUSION: Arterial hepatic perfusion was significantly
      increased after orthotopic liver transplantation, but differences in portal
      venous and total liver perfusion were not significant. Dynamic single-section CT
      might also help evaluate hepatic vascular complications, chronic transplant
      rejection, and hepatic perfusion in liver cirrhosis.

PMID- 9769824
TI  - Hepatocellular carcinoma: power Doppler US with a contrast agent--preliminary
      results.
AB  - PURPOSE: To investigate the value of contrast material-enhanced power Doppler
      ultrasonography (US) in the demonstration and characterization of tumor
      vascularity in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Twenty
      patients with HCC were prospectively evaluated with power Doppler US before and
      after injection of the contrast agent SH U 508 A. The grade and pattern of tumor
      vascularity at power Doppler US were analyzed, along with the degree of tumor
      staining at angiography. RESULTS: Intra- and peritumoral flow signals were
      detected in 19 HCCs (95%) at unenhanced power Doppler US. After injection of
      contrast agent, flow signals increased in 19 lesions (95%). At contrast-enhanced
      power Doppler US, two tumors demonstrated grade 1 vascularity; four, grade 2;
      three, grade 3; and 11, grade 4. At angiography, two tumors demonstrated grade 1
      staining; four, grade 2; eight, grade 3; and six, grade 4. The correlation
      between vascularity grades at contrast-enhanced power Doppler US and at
      angiography was statistically significant (P < .0001). Seventeen HCCs (85%)
      showed the intratumoral or basket pattern of vascularity at unenhanced power
      Doppler US; after injection of contrast material, 15 HCCs (75%) showed the mixed
      pattern. CONCLUSION: Contrast-enhanced power Doppler US is superior to unenhanced
      power Doppler US in the demonstration and characterization of tumor vascularity
      in HCC.

PMID- 9769825
TI  - Complex postcholecystectomy biliary disorders: preliminary experience with
      evaluation by means of breath-hold MR cholangiography.
AB  - PURPOSE: To assess preliminary experience with breath-hold single-shot fast spin
      echo magnetic resonance (MR) cholangiography in complex postcholecystectomy
      biliary disorders. MATERIALS AND METHODS: MR cholangiography was performed in 17
      consecutive patients referred for specialist surgical evaluation of suspected
      complex postcholecystectomy biliary disorders. Two readers, unaware of surgical,
      histopathologic, or other imaging findings, independently reviewed the MR
      cholangiographic images to assess the presence of biliary occlusion, peribiliary
      lesions, nonspecific biliary dilatation (biliary dilatation without an abrupt
      transition in caliber and without a visible underlying cause), bile duct stones,
      or biliary fistulas. Final diagnoses were established with surgery (n = 9),
      imaging other than MR (n = 6), and histopathologic review of the initial surgical
      specimen (n = 2). RESULTS: Final diagnoses were biliary occlusion (n = 8),
      peribiliary lesions (n = 3), nonspecific biliary dilatation (n = 3), bile duct
      stones (n = 2), and biliary-colonic fistula (n = 1). The two readers correctly
      categorized these diagnoses in 15 (88%) and 13 (76%) of the 17 cases, with
      excellent interobserver agreement (kappa = 0.82). CONCLUSION: Single-shot fast
      spin-echo MR cholangiography is an accurate, noninvasive modality for the
      assessment of complex postcholecystectomy biliary disorders.

PMID- 9769827
TI  - Ureteral obstructions and leaks after renal transplantation: outcome of
      percutaneous antegrade ureteral stent placement in 44 patients.
AB  - PURPOSE: To analyze the outcome of percutaneous antegrade ureteral stent
      placement for treatment of ureteral stenoses and leaks after renal
      transplantation. MATERIALS AND METHODS: Antegrade pyelography and percutaneous
      ureteral stent placement were performed in 45 patients with ureteral obstruction
      (n = 40), leak (n = 3), or both (n = 2). Obstructions were graded as mild,
      moderate, or complete, and as early (< or = 3 months after transplantation) or
      late (> 3 months). RESULTS: The outcome of stent placement was successful in 25
      (57%) patients (average follow-up, 30 months). The ureteroneocystostomy (UNC) was
      the most common site of obstructions (22 of 41), leaks (four of five), and
      successful outcomes (16 of 22). Moderate obstructions were most common (29 of 41)
      and responded best to treatment (17 of 29). Eighteen (69%) of 26 early
      obstructions and five (33%) of 15 late obstructions were successfully managed
      percutaneously. All complications (12 of 45 patients) were minor, with infections
      the most common (n = 7). No mortality or allograft loss was attributable to stent
      placement. CONCLUSION: Ureteral stents are safe and effective for the treatment
      of obstructions and leaks and are particularly effective for early and UNC
      obstructions. These stents may also be useful for temporary drainage.

PMID- 9769826
TI  - Gadolinium-enhanced excretory MR urography after low-dose diuretic injection:
      comparison with conventional excretory urography.
AB  - PURPOSE: To evaluate the clinical utility and morphologic accuracy of gadolinium
      enhanced excretory magnetic resonance (MR) urography after low-dose diuretic
      injection and to correlate the results with those of conventional urography.
      MATERIALS AND METHODS: In 71 patients with urologic symptoms, excretory MR
      urography was performed after intravenous injection of 5-10 mg furosemide and, 30
      60 seconds later, 0.1 mmol of gadopentetate dimeglumine per kilogram of body
      weight. The MR urograms were interpreted by three radiologists, who were blinded
      to the clinical outcome, and subsequently compared with conventional urograms.
      RESULTS: Injection of furosemide before contrast material led to rapid, uniform
      gadolinium distribution inside a sufficiently distended collecting system such
      that there was no excessive concentration of gadolinium in the urine. In patients
      with normal or moderately reduced excretory function, this effect allowed
      complete visualization of the urinary tract within 5-20 minutes of contrast
      material injection while minimizing gadolinium-related endoluminal T2* effects.
      The clinical course helped verify almost all MR urographic results. The MR
      urographic technique was significantly superior to conventional urography in the
      assessment of the ureters and bladder (P < .0001). Delineation of small caliceal
      abnormalities is still problematic. The best depiction of the pelvicaliceal
      system was obtained with fat-suppressed MR imaging, although it was still
      slightly inferior to conventional urography (P < .05). CONCLUSION: Gadolinium
      enhanced excretory MR urography performed after low-dose diuretic injection is a
      promising and accurate alternative to conventional excretory urography for
      imaging the morphology of the urinary tract.

PMID- 9769828
TI  - Locally advanced prostatic cancer: long-term toxicity outcome after three
      dimensional conformal radiation therapy--a dose-escalation study.
AB  - PURPOSE: To determine the long-term effects of 75.6- and 81.0-Gy doses of three
      dimensional conformal radiation therapy in a dose-escalation study in patients
      with stage T2c-T3 prostatic cancer. MATERIALS AND METHODS: Fifty patients
      received an initial 75.6-Gy dose, and the dose in 46 patients was subsequently
      escalated to 81.0-Gy. Median follow-up was 60 and 40 months, respectively.
      RESULTS: The rates of effects of acute toxicity during the course of treatment
      were similar for both dose levels. Among the 96 patients, the rate of grade 2
      morbidities necessitating medication to relieve acute symptoms was 17% (16
      patients) for rectal and 36% (35 patients) for urinary morbidities. All other
      patients had either no or grade 1 morbidities. Fourteen patients (15%) developed
      late grade 2 rectal morbidities. There were no differences in 5-year actuarial
      rates of late grade 2 rectal or urinary morbidities among patients who received
      75.6 Gy versus those who received 81.0 Gy. One patient treated with 81.0 Gy
      developed a grade 3 urethral stricture, which was resolved with dilatation.
      CONCLUSION: Tumor dose escalation beyond conventional radiation doses for
      localized prostatic cancer is feasible when delivered with three-dimensional
      conformal radiation therapy, with no increase in morbidity in normal tissue.

PMID- 9769829
TI  - Chorioamniotic separation after second-trimester genetic amniocentesis:
      importance and frequency.
AB  - PURPOSE: To determine the frequency and importance of chorioamniotic separation
      (CAS) after second-trimester genetic amniocentesis. MATERIALS AND METHODS: In
      part 1 of the study, ultrasonography (US) databases were reviewed for cases of
      CAS. In part 2, a study population of 388 women undergoing amniocentesis
      underwent directed US examination for assessment of CAS 15 minutes and/or 2 weeks
      after amniocentesis. CAS, when present, was graded. A control population
      consisted of 363 women undergoing amniocentesis in whom the membranes were not
      assessed. RESULTS: In part 1, a review of 23,883 records revealed seven cases of
      complete CAS, with three deaths, two preterm deliveries, and one emergency
      cesarean section delivery due to fetal distress. In two of these cases, there
      were extremity deformities at birth. In part 2, CAS was present in 98 (25%) of
      388 women at some point. There was no association between CAS and procedural
      variables. There was no substantial difference in morbidity between patients with
      and those without CAS, between patients with different grades of CAS, or between
      the study and control populations. CONCLUSION: Small degrees of CAS are
      frequently present after amniocentesis but are not detected because the membranes
      are not specifically evaluated. Complete CAS is less frequent.

PMID- 9769831
TI  - Juvenile idiopathic inflammatory myopathy: exercise-induced changes in muscle at
      short inversion time inversion-recovery MR imaging.
AB  - PURPOSE: To study the effect of exercise on short inversion time inversion
      recovery (STIR) magnetic resonance (MR) images of thigh muscles in children with
      juvenile idiopathic inflammatory myopathy. MATERIALS AND METHODS: Thirty-two MR
      studies were performed in 19 patients with juvenile idiopathic inflammatory
      myopathy who performed stair-stepping exercise for up to 10 minutes (mean, 5.7
      minutes). Baseline T1-weighted (n = 32) and STIR (n = 32) images and STIR images
      immediately (n = 32) and at 30 (n = 24) and 60 (n = 29) minutes after exercise
      were obtained at 0.5 T. Four radiologists graded STIR signal intensity changes,
      in observer performance experiments in which they were blinded to the order of
      image acquisition in relation to exercise. RESULTS: Changes in muscle signal
      intensity were observed on STIR images obtained immediately after exercise in 20
      of 32 (63%) studies. The mean signal intensity score immediately after exercise
      (1.7 +/- 1.0 [SD]) increased compared with the mean baseline score (1.4 +/- 1.1)
      (P = .0005) and resolved by 30 minutes after exercise. The magnitude of exercise
      induced changes correlated with the amount of work performed (r = 0.51, P = .003)
      but not with disease activity or baseline signal intensity when the changes were
      corrected for work (r < 0.17, P > .35). Radiologists demonstrated moderate to
      substantial agreement in the grading of signal intensity changes after exercise
      (kappa = 0.60-0.84). CONCLUSION: In patients with juvenile idiopathic
      inflammatory myopathy, stair-stepping exercise induces signal intensity changes
      on STIR MR studies of muscle for approximately 30 minutes after exercise, in a
      distribution that may mimic active muscle inflammation.

PMID- 9769830
TI  - Mechanisms of severe, immediate reactions to iodinated contrast material.
AB  - PURPOSE: To measure and elucidate the mechanisms of presumed mediators of
      unexpected severe, immediate reactions to iodinated contrast materials. MATERIALS
      AND METHODS: In a multicenter study, 20 patients with mild to severe reactions to
      iodinated contrast material and 20 control subjects without reactions were
      evaluated. Ionic contrast material was associated with 18 (90%) of 20 reactions.
      Concentrations of plasma histamine, tryptase, urinary methylhistamine, specific
      immunoglobulin E (IgE) against ioxitalamate or ioxaglate, and the anaphylatoxins
      C3a and C4a were measured with radioimmunoassays; complement C3 and C4 levels
      were measured with nephelometry. RESULTS: Histamine levels were increased in 14
      patients; tryptase levels, in 16; and methylhistamine levels, in six. Histamine
      and tryptase values correlated with the severity of the reaction (P < .02 and P <
      .004, respectively). Significantly higher levels of specific IgE against
      ioxaglate (P < .005) and ioxitalamate (P = .045) were found in patients. No
      differences were found for complement fractions. Skin test results in two
      patients with life-threatening reactions were positive for the administered
      contrast material. CONCLUSION: Histamine release and mast cell triggering are
      related to severe reactions. An IgE-related mechanism is strongly suspected.
      Radiologists should be trained to identify and treat anaphylactic shock in
      patients who react to iodinated contrast material.

PMID- 9769832
TI  - Nonossifying fibroma: characteristics at MR imaging with pathologic correlation.
AB  - PURPOSE: To correlate the findings of nonossifying fibroma at magnetic resonance
      (MR) imaging with those at pathologic examination. MATERIALS AND METHODS: In 19
      patients (age range, 8-25 years; mean age, 14 years) with pathologically proved
      nonossifying fibroma, MR images were analyzed for signal intensity and patterns
      of contrast enhancement. Findings at MR imaging and biopsy were correlated.
      RESULTS: On T1-weighted images, all nonossifying fibromas had low signal
      intensity compared with that of skeletal muscle. On T2-weighted images, 15
      lesions (79%) were hypointense and four (21%) were hyperintense. On gadolinium
      enhanced images, intense contrast enhancement was seen throughout 15 lesions
      (heterogeneous pattern in 12 and homogeneous in three) and in the margins and
      septa in four. Extensive hypercellular fibrous tissue and hemosiderin seen at
      pathologic examination were depicted with low signal intensity on T2-weighted MR
      images. CONCLUSION: The distinguishing features of nonossifying fibroma included
      hypointensity and septation on T2-weighted images. Signal intensity on T1- and T2
      weighted MR images and the patterns of contrast enhancement were dependent on the
      amounts of hypercellular fibrous tissue, hemosiderin, hemorrhage, collagen, foamy
      histiocytes, and bone trabeculae.

PMID- 9769833
TI  - Utility of the radial-deviated, thumb-abducted lateral radiographic view for the
      diagnosis of hamate hook fractures: case report.
AB  - To delineate a hamate hook fracture, a radiograph was obtained with maximal
      radial deviation of the wrist and maximal abduction of the thumb. This view is
      easy and cost-effective to obtain, and it may prove helpful in diagnosing
      suspected hamate hook fractures or locating the cause of unexplained ulnar wrist
      pain.

PMID- 9769834
TI  - Breath-hold coronary MR angiography with volume-targeted imaging.
AB  - PURPOSE: To illustrate a new concept for fast coronary artery screening with
      breath-hold volume targeted magnetic resonance (MR) imaging. MATERIALS AND
      METHODS: Ten volunteers and 25 patients were imaged at a field strength of 1.5 T
      with an MR system with phased-array-coil reception and capable of echo-planar
      imaging. End-expiration breath-hold volume localization of the entire heart was
      performed with three-dimensional (3D) multishot segmented echo-planar imaging in
      16-22 heartbeats. Interaction with a multiplaner reformation platform provided
      the optimal double-oblique volumes necessary to target seven coronary artery
      segments. Each segment was evaluated with 24-mm-thick volumes and breath holds at
      end expiration and magnetization transfer-enhanced 3D turbo fast low-angle shot
      imaging in 21 heartbeats. An intravascular contrast agent was used in eight
      patients to improve blood-myocardium contrast for the heart volume localizer
      acquisitions. RESULTS: The entire coronary tree was consistently covered in fewer
      than 13 breath holds. The scheme was successful in all volunteers and in 22
      patients who could achieve adequate breath hold. With end-expiration
      acquisitions, the prescribed 24-mm-thick volumes were reproducible for all
      coronary segments in all cooperative subjects. CONCLUSION: Despite its status as
      the indisputable standard of reference for the detection of coronary artery
      disease, conventional coronary angiography remains costly and highly invasive,
      with associated risks of major complications, including stroke and death. Breath
      hold volume targeted acquisitions permit rapid localization and coverage of the
      entire coronary tree with adequate resolution for evaluating the coronary
      arteries.

PMID- 9769835
TI  - Castleman disease of the thorax: radiologic features with clinical and
      histopathologic correlation.
AB  - PURPOSE: To correlate the radiologic manifestations of thoracic Castleman disease
      with the clinical and histopathologic features. MATERIALS AND METHODS: The
      clinical, surgical, and histopathologic records; chest radiographs; and computed
      tomographic (CT) and magnetic resonance (MR) images in 30 pathologically proved
      cases of thoracic Castleman disease were reviewed. RESULTS: Patients with
      localized Castleman disease (n = 24) typically had the hyaline-vascular type (n =
      23), were asymptomatic (n = 14), and had solitary, well-circumscribed mediastinal
      masses (n = 24). All lesions at contrast material-enhanced CT (n = 13) enhanced.
      All lesions at MR imaging (n = 5) were heterogeneous and had increased signal
      intensity on T1- and T2-weighted images. Three patterns were observed on CT or MR
      images in 20 patients: a solitary, noninvasive mass (n = 10); a dominant
      infiltrative mass with associated lymphadenopathy (n = 8); or matted
      lymphadenopathy without a dominant mass (n = 2). Patients with disseminated
      Castleman disease (n = 6) typically had the plasma cell type (n = 4), were
      symptomatic at presentation (n = 5), and had bilateral mediastinal masses on
      chest radiographs (n = 4). At CT, all lesions manifested with diffuse mediastinal
      lymphadenopathy. All lesions at contrast-enhanced CT (n = 5) enhanced.
      CONCLUSION: Localized Castleman disease manifests as either a solitary, well
      circumscribed mediastinal mass or an infiltrative mass with associated
      lymphadenopathy on CT or MR images. Disseminated Castleman disease manifests with
      diffuse mediastinal lymphadenopathy.

PMID- 9769836
TI  - Thoracic actinomycosis: CT findings.
AB  - PURPOSE: To characterize computed tomographic (CT) findings of thoracic
      actinomycosis. MATERIALS AND METHODS: Chest CT scans and radiographs obtained in
      22 patients with histopathologically proved thoracic actinomycosis were
      retrospectively reviewed. All patients were immunocompetent; they were aged 12-73
      years (mean, 42.6 years; 14 male, eight female). CT findings were correlated with
      histopathologic findings in nine patients who underwent surgery (lobectomy [n =
      8] or segmental resection [n = 1]). RESULTS: All of the lesions were unilateral,
      with an average diameter of 6.5 cm (range, 2-12 cm). Patchy air-space
      consolidation (n = 20) or a mass (n = 2) was seen on CT scans. Fifteen (75%) of
      the 20 patients with air-space consolidation had central areas of low attenuation
      (5-30 mm in diameter) within the consolidation. Thirteen of the 15 patients
      underwent contrast medium-enhanced CT. Ten (77%) of the 13 patients showed ring
      like rim enhancement. Adjacent pleural thickening was seen in 16 patients (73%).
      At histopathologic examination, central low-attenuation areas at CT were seen as
      microabscesses with sulfur granules or a dilated bronchus that contained
      inflammatory cells and Actinomyces colonies. Peripheral enhancement of the low
      attenuation areas was wall of the microabscess or surrounding parenchyma composed
      of granulation tissue rich in vascularity. CONCLUSION: Findings of chronic
      segmental air-space consolidation that contained low-attenuation areas with
      peripheral enhancement or adjacent pleural thickening at CT were suggestive of
      thoracic actinomycosis.

PMID- 9769837
TI  - Acute pulmonary embolism: assessment of helical CT for diagnosis.
AB  - PURPOSE: To determine the sensitivity and specificity of helical computed
      tomography (CT) for the diagnosis of acute pulmonary embolism. MATERIALS AND
      METHODS: This prospective study included 47 patients who underwent pulmonary
      arteriography for evaluation for possible acute pulmonary embolism. Tailored
      helical CT and pulmonary arteriography were performed within 24 hours of each
      other. Each CT scan was interpreted by two chest radiologists, blinded to
      arteriographic results, at two institutions. CT scan interpretations were
      compared with findings on bilateral selective pulmonary arteriograms interpreted
      by two vascular radiologists at one institution. RESULTS: Fifteen (32%) of 47
      patients had angiographically proved pulmonary embolism. For the readers at the
      first institution, helical CT had 60% sensitivity, 81% specificity, 60% positive
      predictive value, 81% negative predictive value, and 75% overall accuracy. For
      the readers at the second institution, helical CT had 53% sensitivity, 97%
      specificity, 89% positive predictive value, 82% negative predictive value, and
      83% accuracy. CONCLUSION: Detection of pulmonary embolism with helical CT may be
      less accurate than previously reported. Given its high specificity but relatively
      low sensitivity, helical CT may not have the ideal attributes of a first-line
      imaging study for the diagnosis of pulmonary embolism.

PMID- 9769839
TI  - The positive bronchus sign.

PMID- 9769838
TI  - Pulmonary nodule detection: low-dose versus conventional CT.
AB  - PURPOSE: To quantitate the effectiveness of low-dose computed tomography (CT) in
      the identification of pulmonary nodules while controlling for anatomic nodule
      characteristics and to establish what factors lead to reduced diagnostic
      sensitivity at low-dose CT. MATERIALS AND METHODS: Each of six participating
      radiologist independently rated 200 image panels by using a four-point confidence
      scale. Conventional images were obtained at 200 mAs; low-dose images were
      obtained at 20 mAs. To fully control their characteristics, nodules were
      simulated with a given diameter, shape, and section thickness while preserving
      the resolution, noise level, and reconstruction artifacts of the original images.
      Panels were matched so that nodules on low-dose and conventional images had
      equivalent sizes, locations, and relationships to blood vessels. RESULTS: Among
      864 positive panels, 259 (60%) of 432 low-dose panels and 272 (63%) of 432
      conventional panels were correctly interpreted (P = .259). Lowering the x-ray
      dose significantly reduced the detectability of peripheral nodules (P = .019) and
      nodules separated from blood vessels (P = .044). Surprisingly, 3-mm nodules were
      detected with approximately equal sensitivity (P = .181) at conventional and low
      dose CT. The specificity of low-dose images was 88% (148 of 168 panels) versus
      91% (153 of 168 panels) for conventional images (P = .372). CONCLUSION: Low-dose
      CT is acceptable for pulmonary nodule identification, making it suitable for
      primary screening. These results confirm the strong effect of size, location, and
      angiocentricity on the sensitivity of nodule detection with conventional CT.

PMID- 9769840
TI  - Combined FDG and [F-18]fluoride whole-body PET: a feasible two-in-one approach to
      cancer imaging?
AB  - PURPOSE: To evaluate the diagnostic usefulness of the combined application of 2
      [fluorine-18]fluoro-2-deoxy-D-glucose (FDG; for the evaluation of soft tissue)
      and [F-18]fluoride (for the evaluation of the skeleton) in positron emission
      tomography (PET) of cancer. MATERIALS AND METHODS: Sixty consecutive patients (23
      women, 37 men; mean age +/- SD, 51 years +/- 14; age range, 13-76 years) were
      entered into this prospective study. Thirty patients underwent only FDG PET.
      Thirty patients underwent combined FDG and fluoride PET. The PET findings were
      correlated with the findings of other imaging modalities. Interobserver agreement
      for the anatomic lesion localization was calculated with the use of the kappa
      statistic. RESULTS: All 30 combined FDG and fluoride studies yielded high-quality
      whole-body images. PET findings correlated with other imaging findings in 54
      (78%) of 69 lesions in the control group and with 64 (88%) of 73 lesions in the
      combined group. Interobserver agreement in the control group was 0.74; it was
      0.95 in the combined group. CONCLUSION: Combined FDG and fluoride PET is an
      advanced metabolic imaging approach for the evaluation of cancer.

PMID- 9769841
TI  - Intra- and extracellular fluorouracil uptake: assessment with contrast-enhanced
      metabolic F-19 MR imaging.
AB  - PURPOSE: To assess the extra- and intracellular uptake of the anticancer drug
      fluorouracil and its major catabolite alpha-fluoro-beta-alanine (FBAL) at
      gadolinium-enhanced fluorine-19 magnetic resonance (MR) imaging. MATERIALS AND
      METHODS: The relative fluorouracil and FBAL F-19 signal intensity increases due
      to extracellular and hepatobiliary paramagnetic contrast media were evaluated in
      ACI rats with transplanted Morris hepatoma. Control rats (n = 6) did not receive
      contrast medium; study rats received gadopentetate dimeglumine (n = 6) or
      gadoxetic acid (n = 6) before intravenous fluorouracil administration. The
      biodistributions of fluorouracil and FBAL were mapped at metabolic F-19 MR
      imaging at about 6 minutes (early distribution phase) and 64 minutes (metabolic
      phase), respectively, after drug administration. RESULTS: Gadopentetate
      dimeglumine induced a significant (P < .05) increase in the signal intensity of
      fluorouracil (70%) in the hepatoma; gadoxetic acid induced a significant increase
      in the signal intensity of fluorouracil in the hepatoma (85%) and of FBAL in the
      liver (71%). The fluorouracil liver signal intensity did not increase with either
      contrast medium. CONCLUSION: Whereas a marked amount of fluorouracil is in the
      extracellular tumor compartment 6 minutes after fluorouracil administration, the
      dominant fluorouracil signal intensity in the liver at 6 minutes arises from the
      intracellular compartment, which can be explained as retention of fluorouracil in
      hepatocytes. The marked increase in the FBAL signal intensity about 1 hour after
      fluorouracil administration is congruent with our observation of a high
      intracellular uptake of gadoxetic acid in the liver at about 1 hour.

PMID- 9769842
TI  - Human breast lesions: characterization with proton MR spectroscopy.
AB  - PURPOSE: To assess the clinical usefulness of spatially localized hydrogen-1
      magnetic resonance (MR) spectroscopy in distinguishing benign from malignant
      lesions on the basis of total choline levels. MATERIALS AND METHODS: These
      studies were performed at 1.5 T with a four-channel multicoil that compresses the
      breast sagittally. Contrast material-enhanced MR imaging and single-voxel H-1 MR
      spectroscopy were performed in 17 patients (age range, 25-68 years) who had
      nonspecific mammographic findings. Histopathologic correlations were made from
      biopsy or surgical specimens. Ten patients had various malignant breast lesions 1
      4 cm in diameter, and seven patients had benign processes. RESULTS: Most studies
      were performed with nominal voxel sizes (< 2 cm3). Spectra obtained with an echo
      time of 31 msec showed resonances from water and mobile fatty acids and, in some
      cases, the N-trimethyl resonance of choline-containing compounds (Cho) at 3.2
      ppm. The absolute concentration of Cho in each lesion was determined with a
      phantom containing 1 mmol/L Cho as an external reference. On the basis of
      reference measurements, the least detectable level of Cho was 0.2 mmol/L. With
      this threshold, seven of 10 malignant lesions showed detectable levels of Cho. In
      contrast, Cho was seen in only one patient with an extremely rare benign process,
      a tubular adenoma. The remaining six patients with benign processes demonstrated
      no detectable Cho levels. CONCLUSION: Spatially localized H-1 MR spectroscopy can
      provide sufficient sensitivity and spectral resolution at 1.5 T to demonstrate
      Cho in human breast lesions with a spectroscopic protocol that provides up to 1
      cm3 resolution. Determining the presence of Cho may provide a useful test for
      malignancy.

PMID- 9769843
TI  - Medial or lateral mammographic lesions: down and out is down and out ...
      sometimes.
AB  - When there is doubt whether a mammographic lesion is medial or lateral to the
      nipple, the "down and out" rule is commonly employed. This states that a density
      moves inferiorly (down) on the mediolateral compared with the mediolateral
      oblique view if it is lateral (out) to the nipple. The author found areas in each
      breast, however, where the down and out rule does not apply.

PMID- 9769844
TI  - Unilateral absence of ureteral jets in the third trimester of pregnancy: pitfall
      in color Doppler US diagnosis of urinary obstruction.
AB  - Among 23 asymptomatic pregnant women with ureteral jets noted at color Doppler
      ultrasonography, jets were detected at only one ureteral orifice in three (13%)
      during the third trimester. In each such case, normal jets were detected from the
      suspicious ureter after the patient turned to the contralateral decubitus
      position. A unilaterally absent jet noted in the third trimester of pregnancy
      should not be interpreted as a sign of ureteral obstruction unless the finding
      persists in the contralateral decubitus position.

PMID- 9769845
TI  - Bone surface lesions.

PMID- 9769846
TI  - US of pancreas in blunt abdominal trauma.

PMID- 9769847
TI  - Endovascular stent-grafts for traumatic thoracic aortic aneurysm.

PMID- 9769848
TI  - Radiologic versus bedside placement of peripherally inserted central catheters.

PMID- 9769849
TI  - Subservience of excretory urography to unenhanced CT in evaluating renal colic: a
      good idea?--benefits and consequences.

PMID- 9769850
TI  - Radiation risk in CT for acute abdominal pain.

PMID- 9769851
TI  - [The first 25 years of the Center for Sociology and Medical Demography (1972
      1997)].

PMID- 9769852
TI  - Proceedings of the 4th FICOSSER General Conference. Federacion Internacional de
      Cooperacion de los Centros de Investigacion sobre los Sistemas y Servicios de
      Salud. Cuernavaca, Mexico.

PMID- 9769853
TI  - [Use of a G-protein-coupled receptor to communicate. An evolutionary success].
AB  - Among membrane-bound receptors, the seven transmembrane receptors are the most
      abundant (several thousand, 1% of the genome). They were the most successful
      during evolution. They are capable of transducing messages as different as
      photons, organic odorants, nucleotides, nucleosides, peptides, lipids, proteins,
      etc. They are catalysts of the GDP/GTP nucleotide exchange on heterotrimeric G
      proteins. They are therefore also called 'G-protein-coupled receptors' (GPCR). G
      proteins are composed of three subunits, G alpha and two undissociable subunits,
      G beta gamma. There are at least three families of GPCR showing no sequence
      similarity. Among G proteins, some have been crystallized (including under the
      heterotrimeric form) and their structure as well as their activation mechanisms
      are well known. The structures of GPCR are less known owing to the difficulty in
      crystallizing membrane-bound proteins. Indirect studies (mutations, 2D
      crystallization of rhodopsine, molecular modelling, etc.) lead to a useful model
      of the 'central core' composed of the seven transmembrane domains and of its
      structural modifications during activation. The intimate contact zones between
      GPCR and G proteins include, on the GPCR side, domains of intracellular loops and
      C-terminal, which are specific for each family and on the G protein side,
      essentially the N- et C-terminal domains plus the alpha 4-beta 6 loop. GPCR can
      adopt several 'active' conformations some of them being found in mutated
      receptors responsible for pathologies.

PMID- 9769854
TI  - Multiple mutations in a specific gene in a small population.
AB  - Hereditary diseases have been reported with relatively high frequency in some
      small populations. Founder effect and genetic drift, associated or not with
      selective advantage of heterozygotes in case of recessive diseases, are the main
      explanations. Therefore, if we consider one population and one particular
      disease, only one deleterious allele should be observed. Determination of
      mutations has shown that in most cases the situation is more complex; more than
      one mutation is found among the patients. This finding can be explained by a
      multiple founder effect, with genetic drift and new mutations.

PMID- 9769855
TI  - Increase in rat soleus myotendinous interface after a 14-d spaceflight.
AB  - Myotendinous junctions (MTJs) transmit contractile force from skeletal muscles to
      tendons. The effects of a 14-d spaceflight on MTJ were studied in the soleus
      muscle of male adult Sprague Dawley rats by transmission electron microscopy and
      histomorphometric techniques. We showed that the length of the junctional
      membrane relative to the muscle fiber diameter increased by 58% after 14 d of
      spaceflight. This increase accompanies morphological changes at MTJs. The flight
      MTJs appeared more shredded. The ends of the muscle fibers exhibited T tubule
      dilatation, swollen mitochondria, Z-disk streaming, loss of myofilaments, a
      thinning down of subplasmalemmal densitites, multivesicular bodies and signs of
      junctional membrane and basal lamina remodelling. The ultrastructural
      observations suggest that the increase in myotendinous interface could result
      from the extracellular matrix spreading into remodelling muscle fiber, whereas
      the constraints related to unloading were reduced by spaceflight conditions.

PMID- 9769856
TI  - New antiherpetic nucleoside from a Basidiomycete.
AB  - Antiviral activity was characterized from the culture broth of the Basidiomycete
      Macrocystidia cucumis (Pers. ex Fr.) Heim. When the stationary phase was reached
      (21 d), the culture broth was shown through an ELISA assay to contain antiviral
      activity against herpes simplex virus type 1 (HSV-1), as assessed in baby hamster
      kidney cells (BHK-21). Once the presence of the anti-HSV-1 activity in the
      culture broth was demonstrated, we proceeded with the purification and isolation
      of the active principle using a semi-preparative HPLC technique. The activity was
      associated with a purine nucleoside designated McA. This compound displayed no
      cytotoxicity at antivirally effective concentrations and proved to be a novel
      nucleoside analogue.

PMID- 9769857
TI  - Human genome diversity.
AB  - Human genome diversity studies analyse genetic variation among individuals and
      between populations in order to understand the origins and evolution of
      anatomically modern humans (Homo sapiens sapiens). The availability of thousands
      of DNA polymorphisms (genetic markers) brings analytic power to these studies.
      Human genome diversity studies have clearly shown that the large part of genetic
      variability is due to differences among individuals within populations rather
      than to differences between populations, effectively discrediting a genetic basis
      of the concept of 'race'. Evidence from paleontology, archaeology and genetic
      diversity studies is quite consistent with an African origin of modern humans
      more than 100,000 years ago. The evidence favors migrations out of African as the
      source of the original peopling of Asia, Australia, Europe and Oceania. An
      international program for the scientific analysis of human genome diversity and
      of human evolution has been developed. The Human Genome Diversity Project (HGDP)
      aims to collect and preserve biologic samples from hundreds of populations
      throughout the world, make DNA from these samples available to scientists and
      distribute to the scientific community the results of DNA typing with hundreds of
      genetic markers.

PMID- 9769858
TI  - Evidence of chromosomal inversion using fluorescence in situ hybridization to
      stretched DNA.
AB  - The resolution of fluorescence in situ hybridization techniques (FISH) can be
      improved using techniques of DNA stretching. The so-called DIRVISH technique has
      been used to demonstrate the existence of an inversion involving a small
      chromosomal segment of the long arm of chromosome 14. This inversion was
      suspected, but not proven, in patients with familial Alzheimer disease. Two
      colour FISH using YAC and cosmid probes allowed us to limit the rearranged region
      around YAC 964e2, which encompasses the Presenilin 1 (PR1) gene. The existence of
      small-sized inversions within the genome becomes, thus, open to microscope
      analysis.

PMID- 9769859
TI  - First characterization of the gene RGD1 in the yeast Saccharomyces cerevisiae.
AB  - We identified the ORF YBR260c during systematic sequencing of one region of
      chromosome II of Saccharomyces cerevisiae. This ORF encodes a putative protein of
      666 aa, of which the C-terminal part of the deduced amino acid sequence resembles
      human and yeast Rho/Rac GTPase activating proteins (GAP). An initial study is
      reported in the paper. This gene was expressed in haploid and diploid cells and
      was called RGD1 for related GAP domain 1. Inactivation of RGD1 was carried out
      and phenotypic analysis of the mutant strain revealed only a slight viability
      defect when cells grown in minimal medium were close to stationary phase.
      Northern and western analyses showed that the RGD1 transcript and the
      corresponding protein were still abundant in cells cultivated in YNB during the
      stationary phase. No functional link seems to exist with the highly conserved
      GTPase Cdc42 involved in cytoskeletal polarization and cell polarity.

PMID- 9769860
TI  - [Endogenous retroviral sequences analogous to that of the new retrovirus MSRV
      associated with multiple sclerosis (part 1)].
AB  - Multiple sclerosis (MS) is still of unknown origin and may involve autoimmune,
      genetic and viral components in a pathogenic sequence whose relative importance
      is yet to be determined. A peptide, isolated from the cerebrospinal fluid of MS
      patients, is similar to a fragment of the pol protein reverse transcriptase (RT)
      of the newly reported MSRV retrovirus. The 700 amino acid sequence of MSRV-RT is
      closely related to a novel human retroviral-like sequences. We also identified a
      gag-like sequence upstream of this human genomic RT-like sequence, which allowed
      us to identify altogether 4,000 nucleotides, possibly coding for an endogenous
      retroviruses. Homologous sequences found in other locations in the human genome
      seem to characterize a new family of retroviral endogenous sequences, which may
      be of relevance to multiple sclerosis.

PMID- 9769861
TI  - Overexpression of a Hu-bcl-2 transgene in Lurcher mutant mice delays Purkinje
      cell death.
AB  - Cerebellar Purkinje cells in the heterozygous Lurcher mutant undergo cell
      autonomous degeneration beginning in the second week of postnatal development and
      becoming almost total around 30-45 days. The Lurcher mutation was recently
      identified as gain-of-function defect in the delta 2 glutamate receptor causing a
      constitutive current leak, suggesting that +/Lc Purkinje cells die by an
      excitotoxic mechanism. In previous studies we have shown that overexpression of
      bcl-2, a key regulator of cell death, in the heterozygous Lurcher mutant does not
      prevent +/Lc Purkinje cell death. To investigate further the mechanisms of +/Lc
      Purkinje cell death, we have crossed +/Lc mutants with a second line of Hu-bcl-2
      transgenics (NSE73a) that shows an earlier onset of transgene expression and
      higher expression levels. Analysis of eight +/Lc-NSE73a mutants (4 at 2 months
      and 4 at 5-6 months) showed that Hu-bcl-2 overexpression delayed, but ultimately
      could not prevent +/Lc Purkinje cell death.

PMID- 9769862
TI  - Impact of chloroquine resistance on malaria mortality.
AB  - Over 12 years, from 1984 to 1995, we conducted a prospective study of overall and
      malaria specific mortality among three rural populations in the Sahel, savanna
      and forest areas of Senegal. The emergence of chloroquine resistance has been
      associated with a dramatic increase in malaria mortality in each of the studied
      populations. After the emergence of chloroquine resistance, the risk of malaria
      death among children 0-9 years old in the three populations was multiplied by
      2.1, 2.5 and 5.5, respectively. This is the first study to document malaria
      mortality at the community level in Africa before and after the emergence of
      chloroquine resistance. Findings suggest that the spread of chloroquine
      resistance has had a dramatic impact on the level of malaria mortality in most
      epidemiological contexts in tropical Africa.

PMID- 9769863
TI  - [Comparison of the results of the Etest and the method for determining minimum
      inhibitory concentrations in solid media for penicillin G, amoxicillin, and
      cefotaxime for S. pneumoniae. A multicenter study].
AB  - In 1996-1997 a multicentre study was carried out on 450 Streptococcus pneumoniae
      strains to compare the MICs and susceptibility categories obtained with the Etest
      (AB Biodisk) used under routine conditions in 22 hospital laboratories in the
      Rhone-Alpes region, France, with those obtained by the reference technique of
      agar dilution performed in a single coordinating centre. Each laboratory detected
      penicillin resistant pneumococci (PRP) by the oxacillin disk method (1 microgram
      and 5 micrograms) and determined the MICs of penicillin G (PG), amoxycillin (AMX)
      and cefotaxime (CTX) by the Etest. All the PRP strains were collected in the
      coordinating centre where MICs were carried out. The strains were classified as
      susceptible (S), intermediate (I) and resistant (R) according to the CASFM
      criteria (Comite de l'Antibiogramme de la Societe Francaise de Microbiologie).
      The concordance results based on susceptibility categories are as follows: PG =
      67.6%, AMX = 63.6%, CTX = 71.5%. Minor errors are as follows: PG = 31.2%, AMX =
      36%, CTX = 28.5%. Major and very major errors are rare (0% to 0.6%). Agreement
      within 1 log2 dilution was obtained for about 80% of the strains. The minor
      errors results from strains clustering near the breakpoints 1 mg/l (PG) and 0.5
      mg/l (AMX, CTX), and from practical difficulties in routine use of the Etest.
      These discrepancies may result in severe therapeutic problems. This study
      confirms the limits of the Etest. The authors insist on standardization and
      rigorous use of the Etest under routine conditions.

PMID- 9769864
TI  - [Multifocal tuberculosis. Apropos of 49 cases in the midwest region. GERICCO
      (Group for Epidemiology and Research in Clinical Infections of the Central West
      of France), 1991-1993].
AB  - Diffuse or multifocal tuberculosis (TB) accounts for 9% to 10% of cases of
      extrapulmonary TB and carries a poor prognosis with a mortality rate of 16% to
      25%. Forty-nine cases of multifocal TB defined as involvement of two
      extrapulmonary sites with or without pulmonary TB were reviewed. Mean patient age
      (+/- SD) was 50 +/- 18 years. Twenty-three per cent of patients were immigrants.
      A history of TB and contact with a TB patient were found in 23% and 18% of cases,
      respectively. Of the 52% of immunocompromised patients, 38% were HIV-positive.
      The skin tuberculin test was positive in 67% of cases. Mean time from symptom
      onset to admission was 80 +/- 77 days (median, 58 days). The 49 patients had a
      total of 128 TB foci. Six patients had positive blood cultures. The tubercle
      bacillus was recovered from the extrapulmonary sites in 88% of cases. Mean
      treatment duration was nine months. Recovery from the TB was achieved in 64% of
      cases. The overall mortality rate was 47%, and 33% of patients died as the direct
      result of TB. Most deaths occurred in immunocompromised patients. A high index of
      suspicion for multifocal TB should be maintained in immunocompromised patients,
      even those who test negative for the HIV.

PMID- 9769865
TI  - [Bacteria isolated from protected bronchopulmonary samples: variation as a
      function of the previous length of stay in the recovery room].
AB  - We retrospectively reviewed the variation of the organisms recovered from 403
      protected bronchopulmonary specimens in three surgical intensive care units
      according to the time elapsed from admission. The predominant pathogens during
      the four first days were Haemophilus influenzae (33.3%), Staphylococcus aureus
      (18.2%), mostly methicillin susceptible strains, and Streptococcus pneumoniae
      (14.3%). After the fourth day, they were progressively replaced by typical
      nosocomial bacteria such as methicillin resistant Staphylococcus aureus,
      Pseudomonas aeruginosa and Acinetobacter baumannii. For Pseudomonas aeruginosa
      and cephalosporinase-producing Enterobacteriaceae, strains resistant to third
      generation cephalosporins occurred significantly later than the susceptible
      strains. These results indicate that the time elapsed from intensive care unit
      admission has a major influence on the bacteriology of respiratory tract
      infections, but no clear cut-off point between early-onset and late onset
      pneumonia is evident.

PMID- 9769866
TI  - [An Acinetobacter baumanii outbreak at the Versailles Hospital Center].
AB  - A. baumannii is a multiresistant bacteria which is recognised as responsible for
      nosocomial infections and hospital outbreaks. The control of these outbreaks
      depends on the strain's typing and on the fight's policy against nosocomial
      infections. An outbreak of A. baumannii is occurred to patients who were
      hospitalized in Centre Hospitalier de Versailles. To investigate this outbreak,
      we have determined the biotype (Bouvet's method), the succeptibility pattern
      (disk diffusion and agar dilution results were analysed with the hierarchical
      classification and main component analysis) and the total DNA macrorestriction
      pattern (Pulse Field Gel Electrophoresis using SmaI restriction enzyme). A risk
      factors for A. baumannii acquisition were delineated in case-control study.
      During 2 years, 38 patients have been infected or colonized to A. baumannii.
      Thirty two patients were hospitalized in ICU. We studied 38 non repetitive
      clinical isolates and 9 strains of the patient's rooms. Four biotypes were
      defined by the Bouvet's typing method. Fourteen groups were obtained when
      succeptibility results were analysed with the hierarchical classification and 6
      with the main composant analysis. The molecular typing permit us to define 4
      epidemic and 6 sporadic strains. All the epidemic strains were isolated on ICU
      hospitalized patients. Our study has shown wide contamination in patient's rooms
      (Water tap, dry surfaces, patient's mattresses...). Environmental objects have
      been a major risk factor for A. baumannii acquisition. The control of this
      outbreak has been possible by application of hygienic measures (hands washing,
      isolment, meticulous cleaning of the ICU and environmental controls). No new case
      is occurred in the last year. Typing methods and case-control study are necessary
      to investigate cross-infections and take efficient measures against these
      outbreaks.

PMID- 9769867
TI  - [Systematic detection of toxigenic strains of Clostridium difficile--is it
      useful?].
AB  - The incidence of Clostridium difficile (Cd) infection is rising and Cd in fact is
      now endemic in many hospitals. During the past 4 years we analyzed our data
      concerning diarrhea caused by Cd in our 700 beds hospital. A positive case was
      defined as a Cd cytotoxine positive with or without positive culture for Cd. In
      the present study 120 episodes of Cd associated diarrhea occurred in 102
      patients. 1101 stools were cultured from 921 patients. Since 1995 we choose to
      systematically evaluate Cd in diarrheal stools from hospitalized patients. 120
      stool were positives (102 patients), we observed a significant difference between
      the 2 study periods: Cd was recovered from 16.9% of stool specimen during 1993
      1994 and from 9.6% since 1995. This study clearly confirm the common role of Cd
      in our hospitalized patients as in all positive case, Cd was the only
      enteropathogen isolated. We suggest the systematic investigation of Cd in
      hospitalized patients.

PMID- 9769868
TI  - [Impact of hospital infection on medical expenditures in a continuing care and
      rehabilitation service at a geriatric hospital].
AB  - The costs of medical expenditures such as drugs, medical devices (MD), biological
      assays and nurses workload, were measured, before and after the onset of
      nosocomial infection (NI), in rehabilitation care departments of a 1000-beds
      geriatric teaching hospital. Data were collected retrospectively in medical
      records and nursing records. Nurse's workload was measured by the French
      indicator "Soins Infirmiers Personnalise a la Personne Soignee" (SIIPS). A week
      before and a week after the diagnosis of hospital-acquired infection, medical
      consumptions were compared. During the study 38 of the 206 patients admitted in
      rehabilitation care wards presented hospital-acquired infection. Data were
      collected for 31 of these 38 patients. Nosocomial infections are associated with
      an increased pharmaceutical dispensing: medication (mainly antibiotics) and
      medical device's cost; and an increased nurse's workload. This study suggests
      that infection surveillance may be helpful to a better understanding of
      pharmaceutical dispensing variation in geriatric rehabilitation care departments.

PMID- 9769869
TI  - [Epidemiology of hospital bacteremias in eastern France. Eastern CCLIN Network].
AB  - Bacteremia occurs frequently among critically ill patients. The aim of this study
      carried out in Eastern France was to describe the epidemiology of nosocomial
      bacteremia and to assess the methicillin-resistance of Staphylococcus aureus
      (SA). Data were collected during a 4 months prospective survey (09/96-12/96)
      carried out among 44 hospitals. We counted 2633 episodes of bacteremia classified
      as contamination (684), nosocomial bacteremia (970) and community bacteremia
      (979). Incidence rate of nosocomial bacteremia was 30.7 per 100 beds in the
      intensive care units. When documented, the origin of the nosocomial bacteremia
      was the most often catheter blood related infection or urinary tract infection.
      Gram positif cocci were predominant among nosocomial bacteremia (53.8%). Among
      Gram negative bacteria (enterobacteria) (31.6%), Escherichia coli was the most
      frequently isolated. SA was methicillin-resistant in 18.3% of community
      bacteremia and in 26.5% of nosocomial bacteremia. Coagulase negative
      Staphylococcus were methicillin-resistant in 25.4% of community bacteremia and in
      60.1% of nosocomial bacteremia. Measures to prevent catheter blood related
      infections and urinary tract infections may be started.

PMID- 9769870
TI  - [Vancomycin-resistant enterococci in pediatric hematology: don't panic!].
AB  - Do immunocompromised children, carrying vancomycin-resistant enterococci (VRE)
      need to be treated? For 3 years, 230 children with chemotherapy and/or bone
      marrow transplantation (BMT) received amikacin for gut decontamination and rinsed
      their mouth with solutions including vancomycin or not, according to the duration
      and severity of neutropenia. Some patients were isolated, others were at home
      with ambulatory treatment. The first-line antibio-therapy was piperacillin
      amikacin-vancomycin in the chemotherapy unit, imipenem-vancomycin in the BMT
      unit. Once-a-week, the laboratory used to check the efficiency of decontamination
      procedures and look for emerging resistant bacteria. Four patients were
      identified as VRE carriers in their gut flora. The fecal carriage was long
      lasting in a single patient, for whom attempts of eradication failed. No patient
      underwent VRE bacteremia. From our experience, it seems reasonable to neglect
      enterococcal eradication, provided that hygienic measures are strictly applied.

PMID- 9769872
TI  - [Invasive pulmonary aspergillosis in AIDS].
AB  - Risk factor for invasive pulmonary aspergillosis in HIV-negative patients include
      neutropenia, corticosteroid therapy, and chemotherapy. Corresponding risk factors
      in HIV-positive patients have not yet been reported. A case-control study was
      conducted at the Bichat-Claude Bernard Teaching Hospital, Paris, France, between
      1991 and 1996. Eight cases were identified. In three cases, the diagnosis was
      documented histologically. Of the remaining five patients, four had a de novo
      lung cavity with a positive bronchoscopy sample, and one had a pulmonary
      infiltrate with a positive bronchoscopy sample in the absence of any other
      potential pathogen. Each case was matched with three controls who were admitted
      during the same period and had CD4 counts lower than 50/mm3. Median age was 38.1
      years in the cases and 38.4 years in the controls. Median CD4 counts were 12.5 +/
      19.2 in the cases versus 19.3 +/- 16.3 in the controls (P = 0.14). No case
      control differences were found for AIDS duration, neutrophil counts at diagnosis
      or during the previous six months, history of corticosteroid therapy or
      chemotherapy, or number of previous opportunistic infections. Cases were more
      likely than controls to have a preexisting lung cavity (3/8 versus 0/24; P =
      0.01) and had spent more time in the hospital during the previous year (7 +/- 4.5
      versus 2.8 +/- 3.2 weeks; P = 0.02). These data do not support a role for
      neutropenia or immunosuppressive treatments as risk factors for invasive
      aspergillosis in AIDS. They suggest that AIDS patients with a lung cavity or
      frequent hospital stays are at increased risk for invasive aspergillosis.

PMID- 9769871
TI  - [Effects of double and triple antiretroviral agents on the HCV viral load in
      patients coinfected with HIV and HCV].
AB  - HIV infection accelerates natural course of HCV infection, but impact of
      antiretroviral treatment on HCV infection is not well known. The aim of this
      study is to compare the change of HCV viral load in patients on combination of 2
      nucleoside analogues and in patients on combination of 2 nucleoside analogues and
      protease inhibitor. HCV and HIV viral load, lymphocyte CD4 counts, alanine
      aminotransferase (ALT) and aspartate amino transferase (AST) were measured before
      and 3 months after starting treatment in 2 groups: Group 1 (n = 15) treated with
      2 nucleoside analogues and Group 2 (n = 15) treated with 2 nucleoside analogues
      and a protease inhibitor. Results show a significant increase in lymphocyte and a
      significant decrease in HIV viral load in the both group but no significant
      change in HCV viral load and in ALT and AST. In conclusion efficiency of anti-HIV
      therapy (combination of 2 nucleoside analogues with or without a protease
      inhibitor) doesn't seem to have any impact on the course of HCV viremia in HIV
      coinfected patients.

PMID- 9769873
TI  - [Importance of antiproteases in the treatment of microsporidia and/or
      cryptosporidia infections in HIV-seropositive patients].
AB  - Diarrhea due to infection with Microsporidium (M) or Cryptosporidium (C) raises
      significant therapeutic challenges in HIV-infected patients. The usefulness of
      protease inhibitor therapy was evaluated in 20 HIV-positive patients with
      positive tests for M and/or C. There were 17 men and three women with a mean age
      of 42.5 years (range, 26-64 years). Two patients had category B disease and 18
      category C disease according to the 1993 CDC classification scheme (CD4 count
      before therapy, 72/mm3; mean viral burden, 4.6 log). Seventeen patients had
      chronic diarrhea (due to M in 12 cases and to C in five), and the remaining three
      patients were asymptomatic M carriers. Clinical symptoms resolved after addition
      to the antiretroviral regimen of indinavir (n = 17) or saquinavir (n = 3). Mean
      weight gain was 10.5 kg. Karnofsky's index improved. Twelve patients, including
      one of the three who were asymptomatic at baseline, had negative follow-up stool
      cultures. The mean CD4 count increase was 125/mm3, and the mean viral burden
      decrease was 1.285 log. These data suggest that protease inhibitors may be
      capable of eradicating M and/or C infection refractory to other treatments. The
      reason for this effect may involve partial restoration of immune function due to
      inhibition of HIV replication.

PMID- 9769874
TI  - [Comparison of the in vitro sensitivity to cidofovir and ganciclovir of clinical
      cytomegalovirus isolates. Coordinated Action Group 11].
AB  - Cidofovir (CDF) or Vistid is a monophosphate nucleoside analogue that inhibits
      the DNA polymerase of herpes viruses including the cytomegalovirus (CMV). CDF is
      active on GCV-resistant strains with a mutation on the phosphotransferase gene
      (UL97). However, DNA polymerase gene mutations that induce resistance to GCV are
      responsible for cross-resistance to CDF. Resistance phenotypes to GCV and CDF
      were determined for 57 CMV strains isolated from blood and urine samples. Sixteen
      strains were recovered after CDF therapy. Of the remaining 41 CDF-naive strains,
      34 were susceptible and seven resistant to GCV. Fifty percent inhibitory
      concentrations (IC50) for CDF were in the 0.2-2.6 microM range for CDF-naive
      strains susceptible to GCV. For GCV-resistant strains, IC50 values for CDF were <
      or = 3 microM for strains with a low level of resistance to GCV (GCV IC50 < 30
      microM) and > or = 6 microM for three of the five strains with a high level of
      resistance to GCV (GCV IC50 > or = 30 microM).

PMID- 9769875
TI  - [Clinical importance of the quantification of HIV-1 RNA in cerebrospinal fluid
      for the diagnosis of HIV encephalitis].
AB  - We evaluated prospectively the HIV-1 RNA level in CSF as a marker of HIV
      encephalitis diagnosis. 110 HIV-1 infected patients (mean age: 39 years; sex
      ratio M/F: 94/16) were tested for HIV-1 RNA in plasma and CSF. Lumbar punctures
      were performed to explore cognitive deficit, seizure or fever. HIV encephalitis
      was diagnosed in 15 patients (14%), other CNS disease in 34 (31%), and fever
      without CNS disease in 61 (55%). HIV-1 RNA was detectable in 93% of the plasma
      and in 62% of the CSF. No significant difference was observed in CSF HIV-1 RNA
      between patients with or without HIV encephalitis. CSF HIV-1 RNA was correlated
      with plasma HIV-1 RNA (p < 0.01), CSF protein (p < 0.01) and CSF white cell
      counts (p < 0.01). The absence of any significant difference between patients
      with or without HIV encephalitis, suggests that the CSF HIV-1 RNA level is not a
      good marker for its diagnosis.

PMID- 9769876
TI  - [Productive replication of human cytomegalovirus in primary microglial cells].
AB  - Human cytomegalovirus (HCMV) infection can result in neurological symptoms. In
      vitro replication of the HCMV was studied in primary cultures of microglial cells
      from the central nervous systems (CNS) of human embryos. The microglial cells
      were infected with various amounts of either the AD169 laboratory HCMV strain or
      a clinical HCMV isolate. A specific cytopathic effect occurred within 24 h and
      persisted for two months. Immunocytochemical tests for immediate early and late
      viral antigens done one and three days after the infection demonstrated that 60%
      to 80% of the microglial cells were infected and that 3% to 8% were the site of
      viral DNA replication. Kinetic studies showed accumulation of viral particles in
      the supernatant during the first two weeks after the infection. Prestimulation of
      the cells by PMA 24 h before the infection was associated with increased release
      of viral particles and with an increased percentage of cells expressing late
      viral antigens. The microglial cells of the human embryonic CNS are fully
      permissive targets for the HCMV. The in vitro HCMV model used in this study may
      prove useful for investigating the pathophysiology of HCMV encephalitis, in
      particular after mother-to-fetus transmission of the virus.

PMID- 9769877
TI  - [Infectious sequellae of 913 central catheters in oncology].
AB  - Infections associated with central catheters are a significant source of
      morbidity in cancer patients. The first evaluation done as part of a continuous
      catheter surveillance program included the 913 central catheters inserted in
      1995. Three of these catheters are still in place. All were tunneled
      subcutaneously, and most were inserted via the subclavian route. There were 839
      simple silicone catheters and 74 catheters with a cuff. Two groups were defined
      based on whether the central catheter was inserted for administering inpatient or
      outpatient chemotherapy (n = 704) or for another reason (perioperative care,
      symptomatic or palliative therapy; n = 209). Catheter-related infection was
      defined as an infection at the catheter site or as septicemia retrospectively
      shown to be related to the catheter. The risk of catheter-related infection was
      expressed as the number of cases per 1000 days of catheterization. Reasons for
      catheter removal were distributed in table I.

PMID- 9769878
TI  - [Pore-forming leukotoxins from Staphylococcus aureus: variability of the target
      cells and 2 pharmacological processes].
AB  - The staphylococcal bi-component leukotoxins constitute a family included in the
      super-family of the beta-sheet-structured pore-forming toxins. They may be
      produced by Staphylococcus aureus and by Staphylococcus intermedius and their
      target cells vary according to the molecules. The mode of action proceeds by the
      sequential binding of the class S proteins, then by that of the class F proteins
      at the surface of the membranes. Then, the activation of cellular calcium
      channels precedes the pore formation which seems to be sensitive to several
      monovalent cations. The cell response is inflammatory and includes the
      neosynthesis as well as the secretion of leukotriene B4, interleukin -8,
      histamine. The injection of leukotoxins to rabbits generates cell chemotaxis ,
      vasodilatation, and tissue necrosis. The association of the production of
      leukotoxins with clinical syndromes concerns several aspects of the pathology of
      S. aureus, and confers to these leukotoxins an important role of virulence
      factors.

PMID- 9769879
TI  - [Peptostreptococcus magnus osteoarticular infections after orthopedic surgery. 14
      cases and pathogenicity factors].
AB  - We report a retrospective study of 14 Peptostreptococcus magnus bone and joint
      infections, following orthopaedic prostheses or implantation of fixation devices,
      diagnosed in two Paris hospitals between 1992 and 1996. Five patients experienced
      a knee joint infection after anterior cruciate ligament reconstruction with 4
      artificial grafts, and 9 caught joint or wound infections, after limb traumatic
      injuries or bone neoplastic ruptures involving femur, tibia, calcaneum and
      humerus, treated by arthroplasty or osteosynthesis with implantation of
      biomaterials. Septic arthritis was experienced one week to one year after
      reconstructive surgery, and had evolved for several months to years before
      etiologic diagnosis in 5 cases. Specimens of pus, tissues or removed implants
      produced numerous slow growing small colonies of Gram positive cocci arranged in
      clumps on culture media incubated in anaerobic atmosphere only. In 10 patients,
      the same organism was disclosed in several separate specimens. The identification
      of P. magnus was assessed by the enzyme profile (rapid ID 32A API strips), gaz
      liquid chromatography, catalase and coagulase production, resistance to
      novobiocin and Na polyanethol sulphonate. Antibiotic sensitivity testing
      performed by disc method was constant to penicillin G, amoxicillin, cefuroxime,
      cefoxitin, imipenem and pristinamycin with penicillin G MICs < 0.125 mg/l and
      metronidazole MICs < 1 mg/l. Erythromycin, clindamycin, rifampicin, tetracycline
      and fosfomycin were active against more than 70% of P. magnus. All patients were
      cured after a prolonged course of various antibiotics and surgical removal of the
      foreign material whenever possible. We studied in vitro binding of P. magnus with
      extracellular matrix proteins adsorbed onto biomaterials, by particle
      agglutination assays of latex beads coated with proteins. Eighty one% of strains
      bound to collagen, 69% to fibrinogen and 46% to fibronectin. Comparison of
      orthopaedic strains with strains of other infections and from skin showed a
      correlation between P. magnus from bone and joint infections and their fibrinogen
      binding ability (69% against 20%, p < 0.05).

PMID- 9769880
TI  - [Comparison of the pharmacokinetics of tobramycin administered in a single daily
      dose or in 3 doses in cystic fibrosis].
AB  - An aminoglycoside in association with beta-lactam antibiotic are usually the most
      efficient treatment for Pseudomonas aeruginosa infections in cystic fibrosis
      patients. Tobramycin has the lower MICs than the other aminoglycosides to
      Pseudomonas aeruginosa. The aim of the work was to compare pharmacokinetics of
      tobramycin after once daily (15 mg/kg/day; 11 patients) or thrice daily dose (5
      mg/kg/day; 9 patients) in combination ceftazidime (CAZ 200 mg/day in 3 inj. IVD)
      in sputum and sera for two weeks. No statistical difference in the serum
      concentration obtained in each group of patients was observed between the first
      and the 14th day. Serum concentrations were three fold higher when tobramycin was
      administered in once daily dose. Low through concentrations were quickly
      obtained, but they were slightly higher after thrice daily doses. Bronchial
      concentrations were 2 to 2.5 superior and near the critical concentration of
      tobramycin. The clinical efficacy were comparable in the two regimens.

PMID- 9769881
TI  - [Is the quantitative antibiogram a reliable epidemiological marker for
      Pseudomonas aeruginosa infections? Comparison with pulsed field electrophoresis].
AB  - Epidemiologic supervision of P. aeruginosa infections is a daily care for
      microbiologists. The aim of this study is to evaluate quantitative antibiogram,
      which compare strains by calculation of euclidian distances from inhibition zone
      diameters on agar, compared with pulse field gel electrophoresis (PFGE) results.
      53 isolates of P. aeruginosa obtained from bronchial secretions of 26 patients in
      intensive care unit are typed by conventional disk diffusion test on agar with 11
      usual antibiotics. Dendrogram of euclidian distances is performed by Taxotron
      computer program (P.A.D. Grimont, Institute Pasteur, Paris); results are compared
      with 53 PFGE patterns after restriction with Spe I (Genepath system, BIO-RAD).
      Quantitative antibiogram has a high discriminatory power for beta-lactamin
      resistant strains: 27 isolates from 11 patients clustered in 5 types where PFGE
      discerned 5 patterns. The discriminatory power is low for beta-lactamin sensible
      strains: 26 isolates from 15 patients clustered in 8 types where PFGE discerned
      19 patterns, but serotyping method combined with quantitative antibiogram restore
      a high disriminatory power for beta-lactamin sensible strains.

PMID- 9769882
TI  - [Presumptive tests and molecular hybridization for the identification of
      untypable strains of Streptococcus pneumoniae].
AB  - Five different methods for identification of pneumococci (optochine
      susceptibility, bile solubility, Slidex Pneumo-kit, Phadebact Pneumococcus test,
      AccuProbe DNA test) were evaluated with a total of 280 Streptococcus pneumoniae
      non typable strains. 189 strains were identified as pneumococci according to the
      AccuProbe test results. Among these, 180 strains (95.2%) were optochine sensitive
      (d > or = 12 mm). Bile solubility was seen in 125 (66.1%) of the pneumococci.
      Immunological identifications were respectively positive for 67 and 56 among 140
      strains. By comparison with the DNA/RNA reassociation method, the poor
      sensitivities and specificities of the presumptive identification tests are
      actually demonstrated for pneumococcal non typable strains. Thus, the AccuProbe
      DNA test is seen as the only adequate method for identification of such strains.

PMID- 9769883
TI  - [Interest of gene amplification by PCR for the diagnosis of Mycoplasma pneumoniae
      infections in the child].
AB  - Between december 1996 and february 1998, rhinopharyngeal and tracheal aspirates
      from 165 children exhibiting symptoms compatible with M. pneumoniae infection
      were tested by a PCR method using in the same tube primers specific for M.
      pneumoniae P1 adhesin gene and for a human control gene. The positive cases were
      controlled using culture and/or serology. PCR was positive in 22 out of 165
      samples (13.3%); an evaluation of the clinical and biological data was possible
      in 20 of these infected children. From 17 PCR positive respiratory samples tested
      by culture, 13 (76.5%) grew M. pneumoniae. From 14 serum specimens tested by
      ELISA, 12 exhibited specific IgM (3 of them with low titers); cold agglutinins
      were detected in all 7 tested sera. Only one case was not confirmed by any of the
      3 former markers. The mean age of patients was 8.1 years. The main clinical
      symptoms included fever > 38 degrees C, cough, clinical and radiological
      pneumonia in 90, 95, 50 and 85% of cases, respectively. Neurological symptoms
      were the main clinical manifestation in 3 patients; another child exhibited a
      pneumonia associated to an hemophagocytic syndrome and a bone marrow failure
      which needed a graft. These results emphasize the value of PCR for the rapid
      diagnosis of M. pneumoniae infection in children.

PMID- 9769885
TI  - [Therapeutic sera and immunoglobulins available in France as of 1 January 1998].
AB  - The antisera and immunoglobulins of therapeutical use, commercially available in
      France on January 1, 1998, have been listed. For each preparation the
      pharmaceutical form and status, the way of administration and preservation, the
      dosages, the indications, the side effects and the contraindications are
      detailed.

PMID- 9769884
TI  - [Direct cost of antibiotic therapy prescribed for nosocomial bacteremia.
      Prospective study during 6 months at a CHU (University Hospital Center)].
AB  - A six-month prospective study of costs associated with antimicrobial therapy in
      nosocomial bacteremia was conducted from November 1, 1995 to April 30, 1996 in a
      1837-bed teaching hospital, with the help of the hospital pharmacists and
      hospital hygiene unit. Only the costs due to the antimicrobials themselves were
      taken into account. A total of 238 cases of nosocomial bacteremia occurred during
      the study period. The total direct cost of antimicrobial therapy was 444,931
      French francs (FF), i.e., 6.8% of total expenditures for antimicrobials. Mean
      cost per case was 1869 FF, and was 2.6-fold higher in the 21 patients with
      bacteremia due to more than one organism (P = 0.03). CAses with an identifiable
      portal of entry contributed 75% of the total cost. Portals of entry associated
      with the highest cost included central venous lines (103,928 FF) and urinary
      tract infections (50,810 FF). Although 20% of nosocomial bacteremias due to
      coagulase-negative staphylococci did not lead to antimicrobial therapy, the
      remaining 80% contributed 40.8% of the total cost, followed by nosocomial
      bacteremias due to Escherichia coli with 19.7% of the total cost. Thirty-seven
      patients (15.5%) did not receive specific antimicrobial therapy, for the
      following reasons: death before treatment initiation, transfer to another
      hospital, antimicrobial therapy initiated earlier for another infection elsewhere
      in the body due to a different organism, or other form of treatment. The results
      of this study highlight the need for prevention.

PMID- 9769886
TI  - [Staphylococci and enterococci resistant to glycopeptides: the challenge of the
      year 2000?].

PMID- 9769887
TI  - [Bone densitometry and hormone therapy].

PMID- 9769888
TI  - Angiotensin converting enzyme insertion/deletion polymorphism in French Canadian
      subjects with premature coronary artery disease.
AB  - The insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme
      (ACE) gene has been postulated to be associated with CAD in some populations of
      European descent. As part of a study investigating metabolic and genetic factors
      in subjects with premature coronary artery disease (CAD), we examined the I/D
      polymorphism of the ACE gene in 134 subjects with premature CAD (105 men and 29
      women, mean age 49 +/- 6 years) and 116 control subjects selected for health (71
      men, 45 women; mean age 39 +/- 7 years). Both patients and controls were of
      French Canadian descent. As expected, significant differences were found between
      cases and controls with respect to age, plasma lipoprotein cholesterol, presence
      of smoking, diabetes and high blood pressure after correction for age.
      Multivariate analysis confirms the importance of age, HDL-C levels, smoking and
      apo B levels as determinants of CAD. Allele frequencies of the I and D
      polymorphism were 43.1% and 57.9% in controls, and 48.5% and 51.5% in CAD cases
      (chi 2 = 0.622, p = 0.430). No significant association between the I/D
      polymorphism and conventional cardiovascular risk factors, including plasma
      levels of lipids, lipoprotein cholesterol, diabetes or smoking, was found in
      cases or controls. Furthermore, the presence of the I/D polymorphism did not
      correlate with a history of hypertension or a family history of premature CAD in
      CAD patients. We conclude that, in our selected population, the I/D polymorphism
      of the ACE gene is not associated with CAD, conventional risk factors, or a
      family history of CAD. Although our sample size does not allow sufficient power
      to ascertain that the ACE I/D polymorphism is not associated with CAD, we do not
      recommend the routine measurement of the ACE polymorphism in our population to
      determine cardiovascular risk.

PMID- 9769889
TI  - [ParaSight F in the diagnosis of Plasmodium falciparum malaria].
AB  - The ParaSight F is a new diagnostic test for Plasmodium falciparum infections and
      is based on the detection of a trophozoite-derived antigen, the histidine rich
      protein II (HRP-II). To assess the usefulness of this test, we conducted a
      prospective study and analyzed 62 blood specimens from 38 patients, using thin
      blood films, thick blood films and the ParaSight F test. Compared to thick blood
      film, on samples taken before and during treatment, the ParaSight F test had
      86.4% sensitivity and 100% specificity. In 31.5% of P. falciparum infected
      patients, parasitemia was lower than 1 parasite/1000 red blood cells, with all
      specimens being positive by the ParaSight F test. In 15 cases, specimens were
      negative by thin blood film, but were positive by thick blood film and by the
      ParaSight F test. Two patients had, after their treatment was started, positive
      results by ParaSight F and negative results by thick blood film. Cross-reactivity
      occurred neither with other Plasmodium species, nor in cases of severe
      inflammatory syndrome. Persistence of antigenemia was monitored in 14 patients
      receiving quinine. At day five of treatment, antigenemia persisted in seven
      patients. In conclusion, the ParaSight F test does not allow following up the
      efficacy of treatment, identifying other Plasmodium species, or assessing
      parasitemia. However, because this test is easy to perform and has good
      sensitivity and specificity, it is a useful tool in emergent context, in cases of
      parasitemia lower than the thin blood film threshold, and in cases
      morphologically difficult to decipher.

PMID- 9769890
TI  - Oropharyngeal candidiasis in AIDS patients from Abidjan (Ivory Coast): antifungal
      susceptibilities and multilocus enzyme electrophoresis analysis of Candida
      albicans isolates.
AB  - Multilocus enzyme electrophoresis (MEE) and in vitro antifungal susceptibility
      testing were used to investigate the Candida albicans strain diversity in twenty
      nine AIDS patients from Abidjan (Ivory Coast). All patients were monitored for a
      first episode of oropharyngeal candidiasis and were randomly clustered into three
      groups of therapy: ketoconazole, amphotericin B or nystatin. Oral swabs were
      collected before every treatment, 14 and 30 days after the initiation of the
      therapy; a total of 67 isolates were investigated. No resistant or less
      susceptible isolate to any antifungal agent was found despite the emergence of
      clinical relapses, mainly for patients treated with nystatin or amphotericin B.
      The MEE analysis revealed 27 different electrophoretic types (ETs). Genetic
      distances between ETs were statistically analyzed and represented on a
      dendrogram. The 27 ETs clustered into three groups; in each group, ETs
      represented variants of the same strain. A segregation of the C. albicans
      isolates seemed to be as a function of the serotype.

PMID- 9769891
TI  - [Antigenicity of fresh, cryopreserved, or liquid-medium-preserved human
      parathyroid adenomas].
AB  - We have studied the ability of the cryopreservation and culture techniques to
      reduce the antigenicity of human parathyroid tissue by suppressing HLA DR bearing
      cells. Antigenicity was studied with an immunoperoxidase technique applied on
      frozen sections. Antibody against HLA DR, CD1a, CD3, CD22, CD45RA, CD68 and H et
      Y antigens were used. In fresh parathyroid tissue, endothelial cells, histiocytes
      and interstitial dendritic cells expressed HLA DR antigens. Antigenicity of
      cryopreserved tissue were not altered. In cultured tissue, interstitial HLA DR
      bearing cells have disappeared but antigenicity of endothelial cells were not
      modified.

PMID- 9769892
TI  - Pseudomonas aeruginosa from cystic fibrosis patients: study using whole cell RAPD
      and antibiotic susceptibility.
AB  - Pseudomonas aeruginosa is the most important bacterial pathogen in lung disease
      of cystic fibrosis patients. Different morphotypes of the bacterium are
      frequently recovered in sputum samples of these patients. We developed a whole
      cell Randomly Amplified Polymorphic DNA (RAPD) technique in order to establish
      the relatedness between morphotype, genotype and antibiotic susceptibility. Six
      cystic fibrosis patients already colonized by P. aeruginosa were investigated by
      collecting three successive sputum samples (before and after antibiotic
      treatment, and one month later) and selecting 10 isolates per morphotype. 250
      isolates of P. aeruginosa were recovered from 16 of 18 sputum samples. Five
      patients carried a single RAPD type strain four of which showed at least two
      morphotypes; one patient carried two RAPD types strains. No patients carried the
      same strain. These results confirmed other studies previously published in
      showing stability of the chronic colonization with a single strain. Antibiotype
      differences were not associated with differences of RAPD profiles and no relation
      was found between antibiotype and morphotype.

PMID- 9769893
TI  - [Efficacy of an ultraviolet device for the disinfection of radiology cassettes].
AB  - The antimicrobial efficiency of a disinfection box of radiology cassettes, by
      means of a device which emits ultraviolet rays, was studied according to a method
      defined by the laboratory. Germ-carriers contaminated with Staphylococcus aureus,
      Pseudomonas aeruginosa and Candida albicans were irradiated and compared to non
      irradiated reference ones. The bactericidal and fungicidal efficiency was better
      than 99.9% in 5 minutes of irradiation. This procedure represents an interesting
      alternative to the chemical treatment of radiology cassettes.

PMID- 9769894
TI  - [Streptococcus pneumoniae of lesser sensitivity to penicillin in the Sfax region,
      Tunisia (1994-1995)].
AB  - In the last fifteen years, the frequency of Streptococcus pneumoniae resistance
      to penicillin has been regularly increasing with various degrees in different
      geographical zones. In order to determine the epidemiological situation in our
      region, we studied penicillin G susceptibility of S. pneumoniae strains isolated
      in our laboratory for 2 years 1994 and 1995. The S. pneumoniae strains with
      reduced susceptibility to penicillin G (PSDP) were detected by oxacillin screen
      test (using 1 microgram oxacillin disk) and completed with the determination of
      penicillin G MIC. We isolated 107 S. pneumoniae strains (41 in 1994 and 66 in
      1995); 12 of them had reduced susceptibility to penicillin (11.2%). The study
      showed a difference in the percentage of penicillin susceptibility between
      invasive (5.1%) and non invasive strains (28.6%). The rate of strains with
      reduced susceptibility to penicillin increased from 7.3% in 1994 to 13.6% in 1995
      with a higher degree of resistance in 1995. We concluded that our region is not
      spared from the problem of the decreased susceptibility to penicillin G of S.
      pneumoniae. These results should prompt us to survey the evolution of such
      resistance.

PMID- 9769895
TI  - [Fungal and parasitic nosocomial infections: importance and limitations of
      disinfection methods].
AB  - Due to the increase of opportunistic mycosis and parasitosis for several years,
      the management of fungal and parasitic risk in hospital has become a necessity
      and an obligation. The authors remind the main rules and knowledges essential to
      an optimal management of the fungal and parasitic disinfection in hospital. They
      summarize the efficiency of different disinfection processes in relation to
      yeasts, filamentous fungi, Pneumocystis carinii, Cryptosporidia and Microsporidia
      involved in hospital pathology.

PMID- 9769896
TI  - [Radioimmunotherapy of lymphomas and leukemias].
AB  - Radioimmunotherapy offers an exciting new therapeutic modalities for patients
      with recurrent hematologic malignancies or resistant to conventional
      chemotherapy. Clinical trials involving hematologic malignancies have produced
      more impressive results than these involving solid tumors. In recurrent non
      Hodgkin's lymphoma Seattle trials have demonstrated objective responses in 90% of
      patients, complete responses in 85% of patients, a progression free survival of
      62%, and an overall survival of 93% with a median follow-up of 2 years. In
      recurrent acute myelogenous leukemia, or myelodysplasia treated with radiolabeled
      antibodies, total body irradiation, and high dose chemotherapy 67% of patients
      remain disease free with a median follow-up of 33 months.

PMID- 9769897
TI  - [Antisense oligonucleotides: a new therapeutic approach].
AB  - The use of antisense oligonucleotides as therapeutic agents has generated
      considerable enthusiasm in the research and medical community. Oligonucleotides
      inhibit gene expression by binding to their target nucleic acid with high
      specificity and selectivity. The field of antisense technology has progressed
      enormously. Major progress has been accomplished in the synthesis and
      manufacturing of modified oligonucleotides. Numerous studies have demonstrated
      the ability of antisense oligonucleotides to modulate gene expression, in such
      diverse fields as infectious diseases, cancer, and inflammation. More than a
      dozen of clinical trials using antisense oligonucleotides have been initiated
      during the last three years or so. The insights gained through these ongoing
      clinical trials has opened the pathway to the design of more advanced chemistries
      which have improved safety profile and efficacy.

PMID- 9769898
TI  - [Impact of the method and timing of administration on the systemic transport of
      ketoprofen].
AB  - The pharmacokinetics of the non-steroidal antiinflammatory drugs are influenced
      by circadian rhythms and ketoprofen (K) absorption by food, to investigate the
      influence of these two factors, 12 subjects were treated, in random order, orally
      by a fast release tablet (FR 100 mg), by a fast-slow release tablet (FSR 150 mg)
      and by an intramuscular solution (i.m. 100 mg). The 3 treatments were
      administered, with a standardized meal, at 8 h a.m and 8 h p.m, and also at 1 h
      p.m with FR. The daily dosing was 300 mg by oral administration and 200 mg by
      i.m. route. Serum concentration profiles of K were determined by HPLC. The
      pharmacokinetic parameters of K were not modified by the time of intramuscular
      injection. The oral absorption of K (Tmax) was significantly delayed at 1 h p.m
      and more even at 8 h p.m. The maximal serum concentration (Cmax) was
      significantly decreased at 1 h p.m (about 50%, p < 0.001) and also at 8 h p.m.
      The oral bioavailability, evaluated by the area under the K serum concentration
      curve, was not modified, those of FSR was significantly lower than FR (6%, p <
      0.05). This study shows that the time of K administration delayed the Tmax and
      food decreased the Cmax without loss of bioavailability.

PMID- 9769899
TI  - [Bacterial antibiotic resistance: a public health challenge?].

PMID- 9769900
TI  - [Antibiotic resistance in the European countries].
AB  - The overall level of resistance to antimicrobials is high in Europe, most notably
      in intensive care units. Variations exist across countries, with the levels being
      highest in southern Europe. Staphylococcus aureus remains the most hazardous
      pathogen. Glycopeptide-resistant enterococci are relatively infrequent in Europe
      for the time being. Differences in measures used to control antimicrobial use and
      to prevent cross-contamination probably explain country-to-country differences in
      resistance levels. Substantial efforts are needed in both these areas in many
      countries, including France.

PMID- 9769901
TI  - [Surveillance of multiresistant bacteria: justification, role of the laboratory,
      indicators, and recent French data].
AB  - In France, several organizations have given priority status to programs aimed at
      controlling outbreaks of nosocomial infections due to multiresistant bacteria
      (MRB), most notably methicillin-resistant Staphylococcus aureus (MRSA) and
      extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE), thus
      recognizing the widespread distribution and marked pathogenic potential of MRB.
      To evaluate the impact of preventive measures, surveillance systems have been set
      up by bacteriology laboratories. These systems rest on a number of indicators:
      (1) the percentage of strains of a given bacterial species recovered from
      diagnostic specimens that were multiresistant; (2) the number of new patients
      (cases) with recovery of a MRB strain from at least one diagnostic specimen (or
      at least one screening specimen); (3) the incidence, or incidence density, of
      cases per 1000 hospital days or 100 admissions; (4) the distinction between cases
      acquired in and transported to the hospital or department. Studies conducted in
      France between 1990 and 1995 found that the percentage of Klebsiella pneumoniae
      that were multiresistant was around 20% overall and 25 to 35% among nosocomial
      strains, and that the prevalence and incidence of cases were about 0.1 to 0.3 per
      100 admissions. The proportion of S. aureus strains exhibiting resistance to
      methicillin was 35 to 40% overall and 50% among nosocomial strains, and the
      prevalence and incidence of cases ranged from 0.5 to 1 per 100 admissions.

PMID- 9769902
TI  - [Methicillin-resistant Staphylococcus aureus: evolution and epidemiology,
      clinical impact, and prevention].
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) strains have become endemic in
      hospitals in many countries. In most cases, epidemic clones emerge occasionally
      on the endemic background. Early institution of simple measures aimed at
      preventing hand-borne cross-contamination has resulted in low rates of MRSAs in a
      few countries of northern Europe. Although environmental contamination plays a
      role in some cases, colonized or infected patients are the main reservoir. Three
      significant problems have been identified in countries with high levels of
      endemicity, namely identification of the reservoir in the hospital, including
      detection of healthy carriers who are readmitted; notification of departments
      that receive healthy carriers transferred from another department in the same
      hospital or from another hospital; and the increasing and hard-to-control
      reservoir of resistant bacteria in extended-care facilities. These three problems
      are related to the current level of endemicity and to the risk of dissemination
      of resistant strains during hospital-to-hospital patient transfers. The technical
      responses to these problems vary with the environment and available means. They
      include detection of carriers in high-risk units, use of standardized reporting
      forms for patient transfers, and recording of the presence of MRSA in
      computerized medical records. Decontamination of carriers can help to prevent
      cross-contamination in some situations. It is of the utmost importance that all
      the facets of MRSA endemicity be taken into account at the level of the hospital
      as a whole and that all decision makers and health care providers make a
      commitment to reducing MRSA endemicity.

PMID- 9769903
TI  - [Enterobacteria producing extended spectrum beta-lactamases].
AB  - Extended-spectrum beta-lactamases (ESBL) were first observed in 1983. Since then,
      the number and variety of ESBLs have increased rapidly, particularly in France,
      and their distribution is now worldwide. The number of ESBLs has now reached more
      than 30, some of them spreading largely in several countries, such as SHV-4 in
      France. Intensive care units were first involved. Patients from nursing homes may
      recirculate ESBLs into acute care units. ESBL clinical epidemiology does not
      differ from other enterobacteriaceae. Digestive tract is the main reservoir,
      hands are the route of transmission. Infection develops in about 50% of colonized
      patients, more than one-half being urinary tract infections. Risk factors for
      colonization or infection are length of exposure to an epidemic strain and
      frequency of health-care-worker contact. Strategies for containing spreading of
      ESBL-producing strains include use of barrier precautions for carriers. Judicious
      use of antimicrobial agents is also important, by decreasing antibiotic selective
      pressure.

PMID- 9769904
TI  - [Bacteria of the Acinetobacter genus].
AB  - Bacteria of the Acinetobacter genus received little attention for many years
      because of their weak pathogenic potential and changing taxonomy. Since the
      introduction starting in the 1980s of an ever increasing number of
      antimicrobials, these organisms have demonstrated their ability to adapt. They
      are causing an increasing number of nosocomial infections, most notably in
      intensive care units. The selection pressure exerted by antimicrobials and the
      use of increasingly invasive diagnostic and therapeutic procedures are the main
      factors that promote emergence of Acinetobacter in high-risk patients.
      Acinetobacter exhibit a high level of resistance to antimicrobials and are
      capable of persisting in hostile environments (humidity or dryness, presence of
      some antiseptics). As a result, they can cause nosocomial outbreaks.
      Identification of carriers and colonized patients, rigorous isolation, and
      scrupulous cleaning procedures are effective control measures. Despite these
      efforts, however, Acinetobacter baumannii now contributes a significant
      proportion of nosocomial infections.

PMID- 9769905
TI  - [Mechanisms underlying resistance of the bacteria responsible for nosocomial
      infections].
AB  - Resistance of nosocomial bacteria to antimicrobials is due to both natural and
      acquired factors. Production of inactivating enzymes (beta-lactamases,
      aminoglycoside detoxifying enzymes) is the most common mechanism in Gram-negative
      bacteria. The concomitant presence of other mechanisms such as abnormalities in
      the targets (for fluoroquinolones), permeability, or efflux of antimicrobials,
      explains why many nosocomial strains are resistant to multiple drugs. In Gram
      positive bacteria, the main mechanism involves modifications in the bacterial
      targets of antimicrobials; for instance, changes in penicillin-binding proteins
      lead to penicillin resistance in enterococci and to methicillin resistance in
      staphylococci, whereas changes in peptidoglycans result in glycopeptide
      resistance in enterococci. As is the case for Gram-negative bacteria, the
      concomitant presence of other mechanisms is common, and as a result many
      nosocomial strains are multiresistant.

PMID- 9769906
TI  - [Multiresistant bacteria in pediatrics].
AB  - Microorganisms that are resistant to multiple antimicrobial agents are of great
      concern to pediatric clinicians. Children infected with antibiotic-resistant
      bacteria are at risk to not respond to initial therapy. Nosocomial infection of
      pediatric patients with multidrug-resistant organisms are similar to those found
      in adults especially for Staphylococcus aureus, coagulase-negative staphylococci,
      vancomycin resistant Enterococcus and Enterobacteriaceae resistant to third
      generation cephalosporin. However on the contrary to adult patients, multidrug
      resistant bacteria are found in community infections with penicillin-resistant
      Streptococcus pneumoniae and P. aeruginosa in CF patients.

PMID- 9769907
TI  - [Control of nosocomial infections by multiresistant bacteria in geriatric
      services].
AB  - Geriatric wards have a higher prevalence of infection than surgical or acute
      medical wards, and multiresistant organisms contribute a nonnegligeable
      proportion of infections in elderly inpatients. The measures used to prevent
      nosocomial infections in geriatric wards are the same as in other types of wards.
      They include identifying and ensuring the technical and geographic isolation of
      colonized and infected patients. Health care providers should be informed of the
      situation, and antimicrobials used with discernment to avoid the selection of
      multiresistant organisms. Implementation of these measures is made difficult by
      architectural factors, the fact that many geriatric patients require assistance
      in all the activities of daily living, and the long duration of stays in
      geriatric wards. Additional measures are probably essential to achieve long-term
      control of nosocomial infections. Insufficient attention has been given to health
      care providers' perceptions of nosocomial infection and to defining the tasks
      actually performed by these providers.

PMID- 9769908
TI  - [Management of epidemics of nosocomial infections].
AB  - Although nosocomial outbreaks contribute less than 10% of all nosocomial
      infections, they are a significant cause for concern because of their
      unpredictability, frequent association with instrumentation, and potential
      lethality in critically-ill patients. Also, they are commonly due to organisms
      that are atypical or resistant to antimicrobials. As soon as a nosocomial
      outbreak is suspected, a rigorous investigation should be undertaken. After the
      appropriate institutional measures, a case-definition should be developed, and
      the space and time patterns of the cases should be determined. Confirmation
      should be obtained that the number of cases is larger than usual, and working
      hypotheses regarding the source and mode of transmission should be developed.
      Even at this early descriptive stage, recommendations for prevention should be
      made. If needed, the investigation should be carried further by a case-control
      study aimed at identifying risk factors, a molecular analysis of the organisms,
      and examination of samples taken from the environment. A review of hygiene
      procedures is useful in many cases.

PMID- 9769909
TI  - [Comparative study of the bactericidal activity of cefepime and cefpirome in
      association with glycopeptides against Staphylococci sensitive and resistant to
      methicillin].
AB  - The aim of this study was to evaluate by a kinetic time-kill method the synergy
      and bactericidal activity of cefepime and cefpirome in association with
      vancomycin and teicoplanin against 4 coagulase-positive and 7-negative
      staphylococci strains. Among these 2 were susceptible to methicillin and 7
      resistant. Antibiotic concentrations used for time-kill curves were 0.5 and 1 CMI
      for glycopeptides and 32 mg/l for cephalosporins. Bactericidal activity was
      defined as a 3 log10 reduction of the initial inoculum. Cephalosporins at 32 mg/l
      and teicoplanin at 1 CMI were not bactericidal, while vancomycin at 1 CMI was
      bactericidal in 24 to 48 h for 3 strains. Cefepime and cefpirome in association
      with vancomycin were bactericidal against all strains with no secondary regrowth.
      Bactericidal activity was observed for 6 and 9 strains with the combinations of
      cefepime-teicoplanin and cefpirome-teicoplanin respectively. In conclusion,
      despite no significant antistaphylococcal activity of cefepime and cefpirome,
      their association to glycopeptides improved the bactericidal activity of
      vancomycin and teicoplanin.

PMID- 9769910
TI  - Activation and injury of endothelial cells by cytokines.
AB  - Vascular endothelial cells (EC) are primary cellular targets for the actions of
      pro-inflammatory cytokines such as tumor necrosis factor (TNF). We have studied
      the signaling pathways used by TNF that lead to new gene expression (endothelial
      cell activation) or apoptosis (endothelial cell injury). Both responses are
      initiated by ligand binding to TNFR-I (the p55 receptor). TNF initiates
      transcription of the E-selectin gene by activation of the transcription factors
      NF-kappa B and c-Jun/ATF-2. NF-kappa B is activated following degradation of I
      kappa B alpha and I kappa B-beta. Activation of c-Jun/ATF-2 involves new c-Jun
      synthesis, and more importantly, phosphorylation of the amino terminus of c-Jun
      by Jun N-terminal kinase (JNK). Studies in transiently transfected human
      umbilical vein endothelial cells have revealed that NF-kappa B activation is
      initiated through the adaptor protein TRAF-2. The activation of JNK also depends
      upon TRAF-2 and probably involves a kinase cascade initiated by the small G
      proteins Rac-1 and/or cdc-42. Normally, TNF does not injure human EC. However,
      TNF can cause apoptosis of EC when cells are co-treated with either the protein
      synthesis inhibitor cycloheximide (CHX) or the lipid mediator ceramide (cer). The
      pathways leading to apoptosis following treatment with TNF + CHX and TNF + cer
      are different since only TNF + CHX is blocked by the caspase inhibitors crmA
      protein or the peptide zVAD.fmk while only TNF + cer is blocked by the anti
      apoptotic proteins Bcl-2, Bcl-XL or Al. Both pathways may be inhibited by the
      anti-apoptotic protein A-20. TNF does not cause the liberation of cer in EC,
      perhaps because of limited expression of neutral sphingomyelinase-activating
      adaptor protein FAN. These observations suggest that TNF normally acts as an
      activator of EC but may change from an activator to a killer of EC when combined
      with agents that release ceramide, such as u.v. irradiation or cytotoxic drugs,
      or with ceramide mimetics such as lipopolysaccharide. The activation and injury
      of endothelial cells induced by TNF and other proinflammatory cytokines may
      underlie the local effects of these mediators in vivo.

PMID- 9769911
TI  - Endothelial adhesion molecules in health and disease.
AB  - One of the most important events in the reaction to all forms of injury is
      adhesion of leukocytes to endothelium, a prelude to their emigration into
      tissues. This process is central to inflammation, atherosclerosis, and immune
      reactions. Endothelial-leukocyte adhesion is governed largely by the interaction
      of complementary adhesion molecules on endothelia and leukocytes. The synthesis,
      surface expression, and avidity of these molecules, are regulated by chemical
      mediators, particularly chemokines. The most important adhesion molecule pairs
      are the selectins (E, L and P), the immunoglobulins ICAM-1 and VCAM-1, and the
      beta 2 and beta 1 integrins (e.g., LFA-1 and VLA-4). In vivo studies in
      experimental animals and humans have confirmed a role for these molecules in a
      number of pathological processes, including transplant rejection, septic shock,
      atherosclerosis, late phase hypersensitivity reactions, immunologically-mediated
      lung and kidney disease, and reperfusion injury. Besides their importance in
      understanding pathogenesis, work on adhesion molecules has direct clinical
      implications in diagnosis and therapy. Current studies suggest that the
      expression of these adhesion molecules may be a useful marker for active
      inflammation under certain conditions, and that abrogation of endothelial
      adhesion by interfering with such molecules may inhibit tissue injury. Mice
      genetically deficient in adhesion molecules (knock out) have been particularly
      useful in the study of the role of these molecules in vivo. This lecture will
      first summarize the state-of the-art on the structure, localization, and
      distribution of the major adhesion molecules, examine their roles in vivo, in
      humans and knock-out mice, and point to possible use of the information derived
      from these studies in diagnosis and therapy.

PMID- 9769912
TI  - Differentiation of blood-brain barrier endothelial cells.
AB  - The vascular system of the central nervous system is derived from capillary
      endothelial cells, which have invaded the early embryonic neuroectoderm from the
      perineural vascular plexus. This process is called angiogenesis and is probably
      regulated by brain-derived factors. Vascular endothelial cell growth factor
      (VEGF) is an angiogenic growth factor whose expression correlated with embryonic
      brain angiogenesis, i.e. expression is high in the embryonic brain when
      angiogenesis occurs and low in the adult brain when angiogenesis is shut off
      under normal physiological conditions. VEGF receptors 1 and 2 (flt-1 and flk-1)
      as well as the recently identified angiopoietin receptors (tie-1 and tie-2) are
      receptor tyrosine kinases specifically expressed in endothelial cells. Expression
      of these receptors is high during brain angiogenesis but low in adult blood-brain
      barrier endothelium. They are required for the proper development of a vascular
      system, and particularly tie-2 is necessary for brain angiogenesis. Signal
      transduction by these receptors regulates endothelial cell growth, permeability
      and differentiation. Blood-brain barrier endothelial cell characteristics
      (complex tight junctions, low number of vesicles, specialized transport systems)
      are induced by the local brain environment, e.g. neurons and astrocytes. Tight
      junctions between brain endothelial cells are the structural basis for the
      paracellular impermeability and high electrical resistance of blood-brain barrier
      endothelium. Association of tight junction particles with the P-face rather than
      the number or branching frequency of tight junction stands correlated with blood
      brain barrier development and function suggesting that the cytoplasmic anchoring
      of the tight junctions plays an important role. During inflammation, leukocytes
      migrate through blood-brain barrier endothelium. ICAM-1 and VCAM-1 on blood-brain
      barrier endothelial cells appear to be the major mediators of these processes
      while the selectins are absent from brain endothelium in vivo.

PMID- 9769913
TI  - Infiltration of inflammatory cells through brain endothelium.
AB  - The blood-brain barrier (BBB) restricts exchanges of soluble factors and cells
      between the blood and the brain, thus playing a crucial role in maintenance of
      cerebral homeostasis. It is composed of the endothelial cells that line the
      cerebral capillaries. Cerebral capillaries have a number of distinctive
      morphological characteristics, including the presence of tight intercellular
      junctions. Also, the cerebral capillaries are surrounded by astrocytic
      projections that exert a positive regulatory effect on BBB tightness. One effect
      of the BBB is that the number of leukocytes that patrol the central nervous
      system is far lower than in peripheral organs. Nevertheless, massive leukocyte
      infiltration occurs in some disease states: for instance, numerous activated
      leukocytes are found in the cerebral parenchyma in patients with multiple
      sclerosis, and HIV encephalitis is probably due to passage of HIV-infected
      monocytes through the BBB. Compelling evidence has been obtained that the
      perivascular astrocytes and microglial cells, as well as the cerebral endothelial
      cells, locally produce inflammatory cytokines that increase BBB permeability.
      Advances have also been made in the identification of leukocyte adhesion
      molecules expressed at the surface of cerebral endothelial cells. Expression of
      these molecules is induced by inflammatory cytokines. Interactions between these
      adhesion molecules and their leukocyte ligands may induce modifications within
      endothelial cells, including cytoskeleton reorganization and opening of
      intercellular junctions, which may allow leukocytes to cross the BBB. It is to be
      hoped that the new insights gained into the mechanisms of leukocyte penetration
      through the BBB may help to develop novel treatment strategies for
      neuroinflammatory disorders.

PMID- 9769914
TI  - [Role of endothelial nitric oxide in the regulation of the vasomotor system].
AB  - The arterial wall is structurally and functionally compartmentalized. Each
      compartment is characterized by a specific cell type and by specific
      interactions. The endothelial compartment interacts with circulating blood, and
      the adventitial compartment with the surrounding tissue. The media, which
      contains the effector smooth muscle cells, perceives centrifugal messages from
      the endothelium and centripetal messages from metabolically active tissues, from
      adventitial nerve endings, and from peptides produced in the interstitium. The
      degree of contraction or relaxation of the vascular smooth muscle cells
      characterizes the general vasomotor tone, which governs the local blood pressure
      level and distributes the flow according to metabolic needs. The main physiologic
      vasoactive agent is nitric oxide (NO) and is produced by the endothelium. In
      disease states, other agents can become predominant in centrifugal parietal
      messages. NO is produced by type 3 NO synthase, an enzyme that is constitutively
      expressed by endothelial cells. The activity of this enzyme on its substrate,
      arginine, is regulated by the concentration of free calcium and by intracellular
      phosphorylations. Several peptides, including receptors, are coupled to the
      phospholipase C pathway in the endothelial cell; endothelial growth factors such
      as FGF and VEGF, enhance the activity of endothelial NO synthase. However, the
      main physiologic factor responsible for endothelial NO synthase activation is the
      shearing stress produced by friction of the flowing blood against the immobile
      vessel wall. This shearing stress constantly adjusts the diameter of conductance
      vessels to peripheral metabolic needs. Expression of endothelial NO synthase is
      modulated by the chronic effects of the same agents. NO has a vasodilating effect
      that is mediated by the generation of cyclic GMP. Cyclic GMP and cyclic AMP are
      the main second messengers in smooth muscle cell relaxation. NO binds to a heme
      protein, soluble guanylate cyclase, that converts GMP to cyclic GMP. Kinase-G is
      the main target for cyclic GMP in the smooth muscle cell. Kinase-G phosphorylates
      phospholambans and releases the repumping activity of calcium ATPase. More
      importantly, kinase-G phosphorylates the protein G that links seven-domain
      membrane-spanning receptors to phospholipases, thus inhibiting coupling between
      the ligand-receptors interaction and the intracellular signaling process that
      leads to contraction. NO can relax the smooth muscle cell only in the presence of
      a preexisting contractile tone. Conversely, absence of NO enhances the
      preexisting contractile tone. All these notions can be analyzed via the
      experimental model of L-NAME-induced chronic NO synthase blockade in rats. The
      decrease in parietal cyclic GMP seen in this model is associated with an increase
      in contractile tone that translates into systemic arterial hypertension. The
      increase in contractile tone can be blocked by renin-angiotensin system
      inhibitors. Chronic blockade of NO production rapidly induces vascular wall
      phenotype changes that lead to renal failure, ischemic stroke, and fibrosis of
      target organs. These phenotype changes may be related to the increase in the
      oxidative potential of the various types of parietal cells, as suggested by the
      abnormal presence of inflammatory cells and by the increased expression of
      inflammation mediators including cyclooxygenase II, inducible NO synthase, and
      adhesion molecules such as ICAM and VCAM. This model therefore holds promise for
      elucidating interactions between NO and arteriosclerosis. NO system dysfunction
      is also seen in other cardiovascular disorders, including congestive heart
      failure.

PMID- 9769915
TI  - Cell surface metallopeptidases involved in blood pressure regulation: structure,
      inhibition and clinical perspectives.
AB  - Arterial tone and water-electrolyte homeostasis are regulated by several
      peptides, including angiotensin II (AII), bradykinin (BK), atrial natriuretic
      peptide (ANP) and endothelins (ETs). Changing the concentrations of these
      peptides in the plasma, tissue, or urine by decreasing the levels of angiotensin
      II and endothelins and increasing BK and ANP concentrations, is one way of
      modulating the hemodynamic load. The metabolism of these peptides in essentially
      controlled by three enzymes, angiotensin-converting enzyme (ACE), neutral
      endopeptidase (NEP), and endothelin converting enzyme (ECE), which all belong to
      the group of zinc metallopeptidases. Inhibition of these peptidases by a single
      compound (a dual inhibitor) that inhibits at once angiotensin II formation and BK
      and ANP inactivation, causes vasodilatation with reduction in blood pressure with
      reduction in blood pressure and increases natriuresis. The design of these
      inhibitors has often be relied on structure-activity studies, based on active
      site models derived from structural data on thermolysin (TLN). The results of a
      large number of pharmacological experiments and those issued from some clinical
      studies using selective or mixed inhibitors show that in spontaneously
      hypertensive rats, dual ACE/NEP inhibitors such as S21,402 produce dose-related
      decreases (-15 to -40 mmHg) in mean arterial pressure and reductions in left
      ventricular hypertrophy and cardiac size. These compounds produce also an
      increase in urinary levels of BK, ANP and cGMP associated with enhanced urine
      output and sodium excretion. Moreover inhibition of NEP appears to improve the
      cardio- and reno-protective effects resulting from ACE inhibition and could also
      reduce hypertrophy of vascular walls. Inhibition of ECE seems to result in a weak
      reduction in blood pressure, an effect which could be emphasized by using dual
      ECE/ACE or ECE/NEP inhibitors. According to these results mixed dual inhibitors
      could be of great interest for the treatment of severe hypertension and chronic
      heart failure. Potent triple inhibitors blocking ACE, NEP and ECE could also be
      developed.

PMID- 9769916
TI  - [Gene therapy of restenosis].
AB  - Although angioplasty has undergone considerable development, restenosis remains
      an unsolved problem. No drugs have been proved effective in the prevention of
      restenosis. Prophylactic stenting is the only treatment with some efficacy. The
      pathophysiology of restenosis involves both intimal hyperplasia with a major
      proliferative component at the dilated site and geometric constrictive remodeling
      of the artery. Stenting seems to prevent the remodeling but does not prevent and
      may even worsen the intimal hyperplasia. Gene therapy may be effective in
      preventing the proliferative component of the intimal hyperplasia: therapeutic
      genes can be delivered locally to the arterial wall cells at the dilated site
      during or immediately after angioplasty, using viral (e.g., adenoviruses) or
      nonviral vectors. The main candidate genes stimulate a variety of endogenous
      mechanisms whose effects consist in inhibition of smooth muscle cell
      proliferation (Rb gene); sensitization of proliferating cells to the effects of
      cytotoxic substances, thus allowing selective chemotherapy (HSV-tk gene); or
      stimulation of reendothelization (VEGF gene). Other genes have also yielded
      promising results (ecNOs, p21, Coxl, etc.). Clinical application of these
      techniques cannot be envisioned until studies are available proving that the
      delivery methods (transfer vectors or local delivery systems) are completely
      safe, and that the candidate genes are effective in "realistic" models. If these
      hurdles are cleared successfully, preventive gene therapy for gene restenosis may
      well become a clinical reality.

PMID- 9769917
TI  - [Compact genomes].
AB  - The number of procaryotic genomes (both Archaea and Bacteria) completely
      sequenced is rapidly increasing since the publication in 1995 of the first ever
      finished one, Haemophilis influenzae. The small size and "simplicity" of these
      genomes make them ideal models for training in genomic before attacking more
      complex genomes, but they have also great intrinsic interest. Preliminary
      analyses of these compact genomes have detected many orphan genes, even in
      organisms previously extensively studied, as well as many families of duplicated
      genes. A major task now is to identify the function of these orphans by a
      combination of in silico, biochemical and genetic analyses (examples will be
      presented). Several genomes of hyperthermophiles have been or will be completely
      sequenced soon. Many of their genes have commercial (stable proteins), as well as
      medical interest (crystallization of proteins with eucaryotic homologs involved
      in pathogenesis). However, further work with these genomes will require the
      development of genetic tools for these hyperthermophiles. The complete
      understanding of genome evolution, structure and function will require the
      sequencing of many genomes at the different levels of the evolutionary scale.
      Sequencing of genomes from closely related organisms can be relevant to study
      genome plasticity, whilst sequencing of genome from different domains (Archaea,
      Bacteria, Eucarya) can help to reconstruct the Last Universal Common Ancestor
      (LUCA). The latter is a difficult task and will require not only classical
      molecular phylogenetic studies (which can be sometimes greatly misleading) but
      also in depth comparative analyses of all central genetic mechanisms in the three
      domains to infer their respective evolution. The fundamental problem is to
      determine if the compact genome of procaryotes is indeed a primitive one (as
      suggested by the term procaryote itself) or if it has been compacted from a more
      complex one by evolutionary forces related to the procaryotic way of life.
      Finally, taking into account the extreme diversity of procaryotes and their
      metabolism, it should be kept in mind that beside a core of genes essential for
      cellular life, the myriad of procaryotic genomes contain a mine of non essential
      genes with potential commercial or medical application. The total number of these
      genes probably outnumber the total number of eucaryotic genes.

PMID- 9769918
TI  - [The yeast genome].
AB  - The yeast genome has been completed and the almost 6000 proteins from the yeast
      proteome are under analysis. This analysis will contribute to elucidate the basic
      mechanisms of unicellular eucaryotic life. Several aspects of such studies are
      relevant to human health problems. In particular, it should allow the development
      of new fungicides which would be more efficient and specific and would escape the
      complex multidrug cell export systems developed by pathogenic fungi. Also several
      human genes determining hereditary diseases have yeast homologues. The function
      of these homologues can be determined using a series of genetic tools which are
      unique to yeast. These human genes can also be expressed in yeast and be
      submitted to the same tools. Several examples of these approaches will be chosen
      concerning yeast homologues of human membrane proteins belonging to ion channels,
      permeases, cation transport-ATPases or ABC transporters superfamilies.

PMID- 9769919
TI  - [Man and the diversity of his genome. An extraordinary phase in the history of
      population genetics].
AB  - Population genetics is almost eighty years old, but benefited only very recently
      from the advantages of direct DNA analysis. Nevertheless, much knowledge had
      already accumulated and was completely confirmed by the study of DNA markers.
      Major benefits of the latter came with microsatellites. It allowed to discover an
      error made with classical markers but even more seriously with RFLPs, because of
      the practically involuntary sampling of individuals almost exclusively of
      European origin for the detection of polymorphisms. Among other evolutionary
      application of microsatellites, the most attractive is their very recent use for
      dating population separations during the recent migration out of Africa of modern
      humans. They confirm the theory that this expansion was quite recent. Single
      nucleotide substitutions are the major material of evolution, and so far markers
      of this kind were rare. A new method, DHPLC, is excellent for their detection and
      testing. In humans it has been applied almost exclusively to the Y chromosome,
      and in a year it has given a completely new picture of Y chromosome genetics.
      Some applications of statistical methods to genetic geography of classical
      markers and ADN markers will show the power of the geographical approach, and
      therefore the need of a wide collection of population samples, as will be made
      possible by the HGDP (Human Genome Diversity Project).

PMID- 9769920
TI  - [Structural, dynamic and interaction studies of proteins: the example of
      immunology].
AB  - The three-dimensional structure of a protein or of one of its functional domains
      cannot be predicted simply from the amino-acid sequence. It has to be determined
      either in the crystal, generally by X-ray diffraction, or in solution by high
      resolution NMR, or it can be modelled by comparison with a highly homologous
      protein. It cannot be represented simply by an average set of atomic coordinates.
      The dynamics of the molecule is part of its definition. The relative role of the
      structure and of the local and segmental mobility will be illustrated for
      recognition processes, mainly in immunological reactions. A unique conformational
      domain, member of the immunoglobulin superfamily, recognises differently its
      partners for an antigen-antibody reaction or for a cell adhesion process
      involving immunological determinants such as CD2 or CD4. Similar structural
      domains can be observed for completely different amino acid sequences, with the
      same type of dynamical properties, e.g. in neocarzinostatin. Restrained mobility
      of CDR loops and water molecules participation at the interface can explain the
      rapid binding of the ligands in AG/AB reactions, but cellular adhesion involves
      more hydrophobic and rigid interactions. This difference can be related to
      evolutionary aspects. Recognition mechanisms in cellular immunology, e.g. that of
      an intracellular foreign viral protein by a T lymphocyte cell, involve rather
      different biochemical processes in the so-called "peptidic self" model including
      proteolysis and cell surface presentation of the resulting peptides by MHC Class
      I proteins. These complexes are then recognised by the T cell receptors. The
      binding site of the TCR alpha and beta chains are structurally related to the
      antigen binding site of immunoglobulins. The peptide is anchored at both C- and N
      terminals and should possess a restrained mobility. Recognition is thus a similar
      structural and dynamical process as in AG/AB reactions but is more secure due to
      the larger number of epitopes for a single protein.

PMID- 9769921
TI  - Gene expression micro-arrays: a new tool for genomic research.
AB  - Gene Expression Micro-arrays, GEMs, measure the expression levels of thousands of
      genes simultaneously. GEMs utilize microscopic cDNA elements on a glass surface,
      low-volume hybridizations of total cDNA, and two-color fluorescence detection.
      This seminar will present data from GEMs containing thousands of human genes and
      discuss the use of this technology in genomic research.

PMID- 9769922
TI  - [Systematic screening of protein interactions].

PMID- 9769923
TI  - [Systematic research on the function of yeast genes].

PMID- 9769924
TI  - [Programmed mouse genome modifications].
AB  - The availability, in the mouse, of embryonic stem cells (ES cells) which have the
      ability to colonize the germ line of a developing embryo, has opened entirely new
      avenues to the genetic approach of embryonic development, physiology and
      pathology of this animal. Indeed, it is now possible, using homologous
      recombination in ES cells, to introduce mutations in any gene as long as it has
      been cloned. Thus, null as well as more subtle mutations can be created.
      Furthermore, scenarios are currently being derived which will allow one to
      generate conditional mutations. Taken together, these methods offer a tremendous
      tool to study gene function in vivo; they also open the way to creating murine
      models of human genetic diseases.

PMID- 9769925
TI  - [Murine models of hemoglobinopathies].

PMID- 9769926
TI  - [Spatio-temporal control of oncogenesis].
AB  - Experimental carcinogenesis has, until recently, relied on the use of animal
      models in which the tumorigenic process is distantly related to that observed in
      humans. More recently the use of transgenic mice has open new opportunities but
      has also revealed two limitations: firstly, some of the most prominent tumors
      observed in genetically predisposed humans are not observed in the corresponding
      mice; secondly, in most instances mice carrying a totally inactivated tumor
      suppressor gene die early during development. To overcome these difficulties we
      have developed a modular transgenic mouse model for the tissue-specific
      inactivation of the neurofibromatosis type 2 (NF2) tumor suppressor gene.
      Mutations are induced by breeding mice carrying different combinations of null
      and targeted but functional alleles. The regulated induction of tissue-specific
      somatic lesions is achieved by in vivo activation of site-specific recombination
      with Cre recombinase that mediate excision of sequences at specific recognition
      sites (loxP). In this conditional knock-out model, an additional degree of
      sophistication enables to trigger the creation of defined somatic mutations not
      only in a tissue-specific manner but also at a time that is decided by the
      investigator. This approach is made possible by the development of inducible
      regulatory systems. This further development should provide excellent flexibility
      to analyse in detail the consequences of the occurrence in time of the different
      mutations that contribute to tumor initiation and progression.

PMID- 9769927
TI  - [Evaluation of in vitro activity of ofloxacin against 73 strains of Chlamydia
      trachomatis isolated from gynecologic infections].
AB  - The in vitro activity of ofloxacin, levofloxacin, ciprofloxacin, doxycyclin,
      erythromycin and roxithromycin was determined against 73 recent clinical strains
      of Chlamydia trachomatis isolated from genital infections. The MICs 90% were:
      0.4; 0.1; 1.6; 0.2; 1.6 and 0.1 mg/l respectively. 100% of strains were
      susceptible to ofloxacin, roxithromycin and doxycyclin. Erythromycin and
      ciprofloxacin had a lower in vitro activity against C. trachomatis.

PMID- 9769929
TI  - [Islets of langerhans transplantation: what is the future?].

PMID- 9769928
TI  - [In vitro activity of 10 antibiotics including pristinamycin and its two
      components (RP 12536 and 27404) against strict anaerobes].
AB  - The activities of the pristinamycin and its two components (RP 12536 and RP
      27404) were investigated using the reference agar dilution method M11A3, on 175
      anaerobic strains in comparison with that of erythromycin, clindamycin,
      metronidazole, amoxycillin either alone or combined with clavulanic acid,
      piperacillin, cefoxitin, cefotetan and cefotaxime. beta-lactamase production was
      detected for all the 55 B. fragilis group strains and 8/12 Prevotella and 2/18
      Fusobacterium strains, respectively. On the whole anaerobes, resistance rates (%)
      were respectively: RP 27404 (69), RP 12536 (64), pristinamycin (5) erythromycin
      (31), clindamycin (17), metronidazole (7) amoxycillin (24), amoxycillin
      clavulanic acid (2), piperacillin (7), cefoxitin (14), cefotetan (21) and
      cefotaxime (27). RP 27404 and 12536 had low activities on anaerobes but acted
      synergistically as pristinamycin. The greatest anti-anaerobic potencies were
      obtained with amoxycillin-clavulanic acid combination, pristinamycin,
      metronidazole and piperacillin. As resistance was not found for pristinamycin
      among Prevotella, Fusobacterium, Gram+ rods and Peptostreptococcus, this
      streptogramin may be an appropriate agent for the treatment of periodontitis,
      pulmonary, ENT, gynecologic and soft tissue infections where these anaerobes are
      frequently involved.

PMID- 9769930
TI  - Effect of inorganic ions on the oxyhemoglobin dissociation curve of severely ill
      patients.
AB  - We have shown that administration of inorganic potassium phosphates (Pi) to
      patients with severe diabetic ketoacidosis was able to increase the P50 (the PO2
      necessary to achieve a hemoglobin saturation of 50%) by a non diphosphoglycerate
      (DPG) mediated effect. This suggests that the oxyhemoglobin dissociation curve
      (ODC) may be determined not only by pH, temperature, CO2 content and DPG but also
      by plasmatic ions. In order to test this hypothesis we have determined the ODC on
      whole blood in two groups of subjects, 49 control subjects with matching age and
      sex and 49 patients suffering from liver cirrhosis, acute pancreatitis, septic
      shock and acute respiratory distress syndrome. The patients had many ionic
      disorders induced either by their diseases or by the applied treatment. The mean
      ODC of the patients did not differ from the normal values. In contrast, the
      dispersion of PO2 around the saturations values was increased from 5 to 80%
      saturation. A forward regression analysis showed that the DPG level and the
      levels of inorganic phosphates and natrium (Na+) played a significant role in
      determining the position of the ODC according to the following equation: P50
      (mmHg) = 34.5 + 0.225 DPG + 0.62 Pi-0.09 Na+, where DPG is in micromol.gHb-1 and
      Pi and Na+ in mEq.l-1. In separate experiments we showed that the Bohr effect as
      expressed in d (log PO2)/dpH amounted to -0.53, -0.46 and -0.42 for SO2 equal to
      5%, 50% and 95%, respectively. The corresponding values for the temperature
      effect was expressed in d (log PO2)/dT amounted to 0.028, 0.024, and 0.020
      respectively. The fact that ions play an role in regulating the position of the
      ODC of patients with ionic disorders may have therapeutical implications,
      preventive or curative.

PMID- 9769931
TI  - [Determination of alpha 1 antitrypsin phenotypes in plasma using isoelectric
      focusing on this agarose gel].
AB  - Plasma alpha 1 antitrypsin (alpha 1 AT) is the major serine protease inhibitor
      (Pi) in plasma. It is a glycoprotein, which presents many molecular variants.
      Allelic phenotypes are classified alphabetically according to their
      electrophoretic mobility in the Pi (Proteases inhibitor) system. More than 75
      distinct protease inhibitor subtypes have been identified using isoelectric
      focusing (IEF). The major interest for detecting its microheterogeneity is the
      rare possibility of deficient alleles, which are responsible of low amounts in
      the alpha IAT production. The clinical use of the alpha 1AT phenotyping is the
      diagnosis of hereditary alpha 1AT deficiencies. The most common normal phenotype
      is MM; the major deficient phenotypes are MS, MZ, SS, SZ and ZZ. Hereditary
      deficiencies of the Pi, the most common inborn error in European people, lead to
      pulmonary emphysema in young adults or liver cirrhosis in children. IEF on
      polyacrylamide gels is the reference method for alpha 1AT phenotyping, but is
      very difficult to standardize. In the present study, we have developed IEF on
      agarose gels for Pi subtyping within a number of technical improvements. A 0.5 mm
      thin agarose gel (1.6%) is cast on polyester film; focusing is performed using
      carrier ampholines (pH = 4.2-4.9), using a very high voltage. Staining is done
      with a simplified silver nitrate method. The patterns of the different Pi
      phenotypes obtained with our technique are very attractive. The common subtypes
      corresponding to the alleles M1, M2, M3, S, Z are univocally demonstrated.
      Agarose gel allows the advantage of using a non toxic substance. Further the gels
      are easy to produce and the method is accessible to all clinical laboratories.

PMID- 9769932
TI  - [Immunohistochemical characterization of the inflammatory infiltrate in the human
      endometrium prior to in vitro fertilization and embryo transfer].
AB  - Infiltrating leukocyte population appears at the time of implantation in the
      endometrium of human and other mammals with hemochorial placentation. This
      leukocyte population is mainly composed of macrophages and typical granular
      lymphocytes CD56+ CD16-. 63 endometrial samples were studied using
      immunocytochemistry, before IVF and embryo transfer. We evaluated the sensibility
      for the assessment of immunological relevant infiltrating cells, of classical
      histopathologic examination compared with quantitation of leukocyte-common
      antigen antibody immunostaining. 21 samples were thoroughly studied during
      proliferative phase. RESULTS: The sensibility of classical histologic analysis
      for the semi-quantitative assessment of leukocyte population, even when performed
      by an experienced histopathologist, is only 62%. When leukocyte population during
      proliferative phase is dense, it is mainly composed of macrophages and CD56+ CD16
      lymphocytes. CONCLUSION: Immunological reaction already reported around the time
      of implantation may occur at other period of the menstrual cycle. Close
      mechanisms of the control and functions of this characteristic reaction remain to
      clarify.

PMID- 9769933
TI  - Anticoagulant profile of iopamidol and meglumine amidotrizoate and their lack of
      thrombin generation: an in vitro study.
AB  - The aim of this in vitro study was to sketch the subtle anticoagulant profile of
      iopamidol 300 mg l/ml (low osmolality non ionic contrast medium) and meglumine
      amidotrizoate 370 mg l/ml (high osmolality ionic contrast medium) in situations
      where variable amounts of clotting factors are observed and to check whether
      thrombin-generation significantly occurred in non anticoagulated blood-contrast
      materials mixtures. In the first experiment, mixtures of deficient plasmas with a
      routine plasma pool provided different ranges with variable amounts of clotting
      factors II, V, VIII, X, XI and XII. For each clotting factor level studied within
      these ranges, an activated partial thromboplastin time was determined with either
      contrast material loaded thromboplastin (5% v/v) or glucose loaded thromboplastin
      (5% v/v) used as a control. In the second experiment fibrino-peptide A (FpA) or
      modified antithrombin III (ATM) assays were performed in either (9:1) non anti
      coagulated blood contrast materials mixtures or blood-glucose mixtures (control).
      Differing aPTT prolongation profiles were observed when clotting factors V, VIII,
      XI and XII were lowered in the plasma. However, neither iopamidol nor
      amidotrizoate induced an aPTT prolongation with decreasing clotting factor II. In
      the second experiment no significant thrombin generation was observed as both
      blood-contrast materials mixtures showed significantly lower FpA and ATM levels
      (p < 0.001) than glucose control after 5 minutes and 10 minutes incubation at
      room temperature. These findings provide evidence that the use of iopamidol in
      angiographic procedures does not increase risk of clotting or hemorrhage.

PMID- 9769934
TI  - [Validation of a sampling method for the channels of a flexible endoscope which
      is experimentally contaminated].
AB  - The increase of endoscopic actions and infectious risks explains of interest in
      endoscopic material maintenance processing. This purpose study was to set to the
      point and validate a microbiological flexibles endoscopes channels (suction,
      biopsy, air/water) sample method. An inoculum made of faeces contents material
      and microorganisms suspension (Pseudomonas aeruginosa or Candida albicans), at
      low or high concentration, was injected into digestive endoscope's channels. For
      each microorganism, five trials were carried out at both of the two
      concentrations. After incubation, a global channels sample was performed with a
      recovering solution, then a counting was made. A variance analysis (ANOVA)
      concerning restated measures was performed for the whole results. The mean
      difference between the number of microorganisms injected and those recovered's is
      0.114 log (IC95% [+0.088; +0.140]). It does not vary significantly according to
      the micro-organisms (p = 0.69) and the inoculum (p = 0.70). The coefficient of
      variation which is 0.525 (min: 0.010; max: 0.260) shows this method can be
      reproduced. This technique are allowed to be recommended to evaluate and to
      validate manuals and automatics endoscopes maintenance processing.

PMID- 9769935
TI  - Regulation of the expression of the human vimentin gene: application to cellular
      immortalization.
AB  - Vimentin is an intermediate filament protein mainly specific of the mesoderm in
      vivo. In vitro vimentin synthesis is characteristic of proliferating cells,
      regardless of their embryonal origin, and is switched off upon differentiation of
      certain precursor cells. Vimentin gene expression is upregulated in some
      metastatic tumour cells, appearing as a marker of oncogenic progression. The
      vimentin network has been suggested to participate in several steps of viral
      infections. The promoter of the vimentin gene is comprised of multiple elements
      responsible for its complex transcriptional regulation. Among them, an NF-kappa B
      and two AP1-binding sites mediate growth factor responsiveness. Two negative
      elements are present, one of which is deregulated by the HTLV-1 activator protein
      Tax. Transcription factor PEA3, encoded by a member of the ets oncogene family,
      activates the vimentin promoter in mammary tumour cells. In vitro, 878 base pairs
      of the vimentin 5'-regulatory region are sufficient to give high levels of
      transcription. These sequences were coupled to the SV40 large T antigen-encoding
      gene to achieve immortalization of new cell lines, either by transfection of
      primary cultures, or by derivation of cell explants from transgenic mice
      expressing the vimentin-SV40 construct. This allowed us, for instance, to
      immortalize endothelial, myogenic or renal epithelial cells, otherwise difficult
      to maintain in culture without loss of their differentiated phenotypes.

PMID- 9769936
TI  - [Influence of the sickle cell trait heterozygote on energy abilities].
AB  - The sickle cell trait (SCT) is a genetic abnormality of the red blood cell which
      mainly affects people of African descent. It is due to the mutation of only one
      parental gene (one glutamic acid of the chain beta of the globin is substituted
      by one valin). The prevalence of SCT in the black US population is within the
      range of 8-9%. It is increasing in Europe and in Africa where it may reach up to
      40% in some regions. The rate of prevalence of SCT in athletic populations was
      found to be similar to that of the general sedentary population in west African
      countries. SCT is usually asymptomatic. However, SCT has been associated with a
      higher risk of sudden death during exercise. In fact, the substitution of one
      amino-acid modifies the properties of haemoglobin and produces physiological
      disorders such as sickling, less solubility of the deoxidized form and the
      reduction of affinity for oxygen. The sickling phenomenon (formation of sickle
      cells) mainly occurs in some conditions related to the practise of sport (intense
      and/or prolonged exercise, exercise in hypoxic conditions, exercise in heat
      conditions). These sickled red blood cells reduce the speed of capillary flow or
      obstruct the blood vessels which, because of the lack of oxygen, become altered.
      The physical ability of sickle cell trait carriers (HbAS) who practise sport
      should be different from the physical ability of subjects with normal haemoglobin
      (HbAA) because of: 1) potential risks due to their haemoglobinopathy and 2) the
      eventual modification of their performance ability. These two aspects have caused
      controversies among many researchers particularly in line with their
      investigation methods. Nevertheless, the following results seem to be
      established: 1) the ability to perform sprint exercises is not altered in the
      HbAS subjects. Their performances in these events are similar to those of HbAA
      subjects; 2) The ability of HbAS subjects to perform intense and prolonged
      exercise is decreased. Our former results have shown that prolonged aerobic
      efforts in hypobaric hypoxic conditions may be associated with a deleterious
      effect on the performance of HbAS subjects. The damaging consequences on their
      performance in these conditions could be due to tissue oxygen delivery
      limitations.

PMID- 9769937
TI  - T cell-mediated terminal maturation of dendritic cells, a critical transition
      into fully potent antigen presenting cells.
AB  - Dendritic cells (DC) are a special subset of leukocytes characterized by their
      potent ability to activate immunologically naive T cells. We established a series
      of long-term DC lines, termed "XS lines", from the epidermis of newborn mouse
      skin. These lines retain many important features of resident DC in epidermis,
      i.e., Langerhans cells (LC), including surface phenotype, antigen (Ag) presenting
      capacity, and cytokine and cytokine receptor profiles. Working with XS lines, we
      have observed recently that DC undergo rapid and profound changes during Ag
      presentation. Specifically, upon Ag-specific interaction with T cell clones, XS52
      cells: a) begin to secrete several cytokines (IL-1 beta, IL-6, and TNF alpha), b)
      lose the expression of CSF-1 receptor and proliferative responsiveness to CSF-1,
      c) elevate the expression of B7-2 (CD86), and d) lose the phagocytotic and
      adhesive capacities. We propose that these changes represent "T cell-mediated
      terminal maturation" of DC, a critical transition into a fully professional Ag
      presenting cell.

PMID- 9769938
TI  - [Topicality of serologic screening of human immunodeficiency virus infections in
      adults].
AB  - Enzyme immunoassay is the basic method for the detection of antibodies to the
      Human Immunodeficiency Virus (HIV). In spite of the apparent facility of the
      serological screening, the difficulties are real at all stages of the analysis.
      Specimen treatment needs defined rules to avoid contamination. The products
      authorized are listed by the "French Drug Agency". The specificity cannot be less
      than 99.5%, and the sensitivity must be of 100%. Each biologist have to acquire
      its own experience of the tests utilised. To the very recent seroconversions, he
      must define decision criteria for the pursuit or not of the investigations. False
      positive have been observed for patients with autoimmune pathology, but was
      usually related to a disparity between kit lots.

PMID- 9769939
TI  - [A three-dimensional model for in vitro study of the association of three
      antibiotics. Application to the activity of piperacillin, tazobactam and amikacin
      against five strains of enterobacteria as a function of their phenotype of beta
      lactam resistance].
AB  - We described an in vitro 3-dimensional model to study the bactericidal activity
      of piperacillin (P), tazobactam (T) and amikacin (A) in combination against 5
      strains of enterobacteria with different resistance patterns of beta-lactam
      antibiotics. A synergy was defined by calculation of sigma FBCP,T,A = BCp/MBCp +
      BCT/MBCT + BCA/MBCA and classic sigma FBCs for each double combination. The
      therapeutic value of each antibiotic was estimated by comparison of its
      bactericidal concentrations alone and in double or triple combination.

PMID- 9769940
TI  - [Importance of the association ticarcillin-clavulanic acid-amikacin in the
      treatment of severe urinary infections after major urodigestive surgery. Report
      of 59 cases].
AB  - Ticarcillin-clavulanic acid (Claventin) and amikacin were administered in an open
      study to prevent and treat nosocomial urinary tract infections, to 59 patients
      after major urological surgery. Postoperative course was event-free in 44 cases.
      10 patients presented asymptomatic urinary tract infections due to gram negative
      bacilli, that did not require any change in antimicrobial therapy. 5 patients
      experienced symptomatic nosocomial infections, whose one was associated with a
      methicillin-Resistant Staphylococcus aureus septicemia that was treated by
      vancomycin. The urinary tract infections were polymicrobial in only 3 cases. The
      tolerance was quite satisfactory, and the protocol was effective in about 92% of
      cases. The combination of ticarcillin-clavulanic acid-amikacin is valuable and
      can be used as first step therapy to preserve the ecology of the patients.

PMID- 9769941
TI  - The role of p53 in normal cells and in cancer development.

PMID- 9769942
TI  - The DNA binding regulatory domain of p53: see the C.
AB  - The p53 tumor suppressor gene is a critical regulator of normal development
      involved in cell cycle control pathways, such as growth arrest, differentiation
      and apoptosis. The DNA binding activity of p53 is central to its function. In
      addition to the specific DNA binding activity that is confined to the "core"
      domain of the molecule, the C-terminus seems to play an important role in both
      controlling the specific as well as exhibiting a non-specific DNA binding
      activity, which is directly associated with sensing damaged DNA. The C-terminal
      DNA binding activity appears to be regulated by phosphorylation, glycosylation,
      splicing and binding of several factors. The C-terminus seems to recognize single
      and double stranded DNA breaks that occur during DNA replication and
      recombination, as well as following external DNA stress signals. Unless the cell
      manages to correct the DNA damage it has the tempting option to progress towards
      apoptosis. Imagine the C-terminus as a traffic light ensuring the safe "on going"
      through the cell cycle; in case damaged DNA could not be corrected, p53 dependent
      apoptosis or terminal differentiation "signs" are turned on!

PMID- 9769943
TI  - Structures and functions of the tumor suppressor p53.
AB  - The tumour suppressor p53 plays a crucial role in the cellular response to DNA
      damage. The p53 protein is able both to detect sites of DNA damage and to
      interact with DNA in a sequence-specific manner and function in the regulation of
      target gene expression. These two properties map to discrete functional domains
      of the protein, the C-terminus and the central core domain respectively. They are
      essential for integration of a normal cellular response to DNA damage, with
      initiation of either G1 cell cycle arrest or apoptosis. This review considers the
      domain structure of p53 in relation to the protein's various functions, together
      with the importance of tertiary structure and conformational flexibility. The
      precise regulation of p53 function remains to be established, although the
      protein is known to be phosphorylated/de-phosphorylated by a number of specific
      protein kinases/phosphatases. A recent discovery indicates that p53 may be
      activated by autoproteolysis and that proteolytic cleavage is induced by direct
      interaction with sites of DNA damage. This process is reminiscent of the
      bacterial Lex A system and would provide one mechanism for activation of p53 in
      response to cellular DNA damage.

PMID- 9769944
TI  - Post-translational modification of p53 and the integration of stress signals.
AB  - The p53 tumour suppressor protein is a potent transcription factor. p53 is latent
      in cells and can be activated in response to signals arising from a range of
      stresses including DNA damage, hypoxia, nucleotide depletion, viral infection and
      cytokines. Activation of p53 leads either to cellular growth arrest at the G1/S
      or G2/M transitions of the cell cycle or to programmed cell death (apoptosis).
      The mechanism of activation of p53 is poorly understood, as are the factors which
      govern the decision between growth arrest or apoptosis. However, accumulating
      evidence points to a role for multi-site phosphorylation of p53 in mediating
      these events. p53 is phosphorylated at different sites within its N-terminal
      domain by protein kinases which are responsive to UV radiation, cytokines, DNA
      damage and growth factors. At the C-terminus p53 is phosphorylated by protein
      kinases involved in growth stimulation, cell cycle control and apoptosis. While
      little is yet understood about the role of phosphorylation at the N-terminal
      sites, the C-terminal phosphorylation events are each involved in controlling the
      specific DNA binding function of p53, perhaps in a coordinate manner, and may
      also play a role in regulating other functions of p53 such as DNA strand
      annealing and transcriptional repression. Understanding the control of p53 by
      multisite phosphorylation may therefore provide essential information concerning
      the mechanisms of activation of p53, the biological consequences of this
      activation, and the role of p53 as an integrator of stress signals.

PMID- 9769945
TI  - A question of life or death: the p53 tumor suppressor gene.
AB  - The tumor suppressor gene p53 plays a major role in the protection of cell from
      DNA damage. Activation of the protein in response to irradiation or genotoxic
      agents, and possibly by other signals, results in growth arrest at the G1 phase
      of the cell cycle or in apoptosis. While it has been shown that the ability of
      p53 to function as a sequence-specific transcriptional activator is necessary for
      the induction of growth arrest, the mechanism of p53-mediated apoptosis is not
      clear yet. It appears that under some conditions activation of the G1 checkpoint
      will prevent apoptosis, but cellular environment may alter the result of p53
      activation towards cell death. p53 may also directly induce apoptosis through
      several pathways, which may be transcriptionally dependent or independent. The
      outcome--a G1 arrest or apoptosis--will depend on a complex network of regulatory
      signals.

PMID- 9769946
TI  - [Mdm2, p53 and the cell cycle: when well enough is best left alone].
AB  - The mdm2 cellular protooncogene is involved in many human tumors where it has
      been shown to be overexpressed, including sarcomas, osteosarcomas, gliomas and
      others. The Mdm2 protein is believed to be oncogenic by binding and inactivating
      the p53 and Rb tumor suppressor gene products and by activating the E2F-1/DP-1
      transcription factors, thus promoting the G1 to S phase transition. The mdm2 gene
      is activated transcriptionally by p53, thus forming an autoregulatory negative
      feedback loop. This feedback loop is important in normal cells and when cells are
      exposed to various genotoxic agents. By activating its own negative regulator,
      p53 would signal the cells to resume proliferation after a p53-mediated G1 arrest
      in response to DNA damage. The review aims to detail the functions of Mdm2 in
      normal and tumor cells. We also discuss several recent data suggesting that Mdm2
      may exhibit activities unrelated to its well known function as a negative
      regulator of p53 activities.

PMID- 9769947
TI  - p53 as a sensor of carcinogenic exposures: mechanisms of p53 protein induction
      and lessons from p53 gene mutations.
AB  - The p53 tumor suppressor gene encodes a nuclear phosphoprotein with growth
      inhibiting properties, which is activated in cell exposed to various forms of DNA
      damaging stress. The development of human cancer often involves inactivation of
      this suppressor through various mechanisms, including gene deletions and point
      mutations. Most mutations impair the specific DNA-binding capacity of p53,
      therefore allowing cells to proliferate in conditions where cells with intact p53
      function are suppressed or eliminated. Thus, mutation of p53 may provide a
      selective advantage for the clonal expansion of preneoplastic or neoplastic
      cells. The diversity of p53 mutations provides a valuable tool to identify
      important sources of cancer-causing mutation in the human setting. Mutagens and
      carcinogens damage the genome in characteristics ways, leaving "mutagen
      fingerprints" in DNA. Well-characterised examples of such "fingerprints" include
      G: C to T: A transversions in lung cancers in association with cigarette smoke,
      G: C to T: A transversions at codon 249 in liver cancers in association with
      dietary exposure to Aflatoxin B1 (AFB1) and CC: GG to TT: AA tandem dipyrimidine
      transitions in skin cancers in association with UVB exposure. In addition,
      mutations at different codons are not functionally equivalent. The availability
      of crystal structures of p53 protein represents an essential development in the
      understanding of the functional properties of p53 mutants. In the future, it is
      expected that analysis of p53 mutations may provide useful information for the
      diagnosis, prognosis and therapy of cancer.

PMID- 9769948
TI  - [Germline mutations of the p53 gene].
AB  - Germline mutations of the p53 gene are associated to the Li-Fraumeni, a rare
      autosomal dominant syndrome characterized by a wide spectrum of tumours including
      sarcomas, breast carcinomas, brain tumors and adrenocortical carcinomas. In most
      of the cases, tumours will develop in children and young adults. Germline p53
      mutations have been identified in approximately 50% of the families with the Li
      Fraumeni syndrome, and in families which only partially fulfilled the definition
      of the syndrome. Germline p53 mutations are mostly missense mutations, located
      between exon 5 and exon 8, within the DNA-binding domain of p53 and these
      mutations inactivate the transcriptional activity of the protein. In tumours, the
      wild-type allele is usually lost, which indicates, that p53 inactivation fits the
      Knudson model. Identification of a germline p53 mutation in an affected subject
      allows to establish the diagnosis of the Li-Fraumeni syndrome on a molecular
      basis and screening for germline p53 mutations may be performed in 1) families
      including two first degree relatives with cancers belonging to the Li-Fraumeni
      spectrum, one relative being affected before age 45, 2) children or young adults
      with a rare tumour of in the general population, belonging to the Li-Fraumeni
      spectrum, such as adrenocortical carcinoma, and 3) children or young adults under
      age 45 with multiple primary tumours of the Li-Fraumeni spectrum. In contrast,
      the clinical benefit of identifying germline p53 mutations carriers in affected
      families, considering the wide spectrum of tumours associated to this syndrome,
      remains to be established.

PMID- 9769949
TI  - p53 and lung cancer.
AB  - The malignant transformation of pulmonary epithelial cells is the result of
      multistep accumulation of genetic and molecular alterations highly related to
      tobacco carcinogens, involving key mechanisms of proliferation and apoptosis.
      Clonal expansion is the net result of acceleration of cell division and
      inhibition of active cell death (apoptosis). Oncogene activation in lung cancer
      (ras, myc, autocrine growth factor loops) results in acceleration of cell
      division. More importantly, tumor suppressor genes inactivation (p53, Rb, cyclin
      dependent-kinase-Inhibitor p16) at genetic, epigenetic, or post-translational
      level removes important constraints on cell division at G1-check-point increasing
      cell proliferation. p 53 inactivation, through loss of transcription function may
      abrogate both G1-arrest control and apoptosis, thus accelerating clonal
      expansion. It is the most frequent alteration in lung cancer (70% of genetic
      alterations) with some differentiation dependent differences. p53 missense
      mutation is highly concordant with p53 stabilization and immunoreactivity.
      However, 20% of mutations with null phenotype (no p53 protein) provides 20% of
      false negative using immunohistochemistry for evaluation of p53 mutations in lung
      cancer. Rare situations are described with wild type p53 stabilization. p53
      mutational spectrum in lung cancer reveals some specificities: 3 hot spot codons
      (codon 157, 248, 273) are the main target of selective adduct formation from a
      defined chemical carcinogen of cigarette smoke (BP). p53 stabilized mutants
      proteins are the targets for immune recognition in patients, leading to secretion
      of p53 auto-antibodies, and can also elicit T-cell specific cytotoxicity in
      vitro. p53 was not proven to be of prognostical importance once the tumor has
      developed. However, p53 stabilization is one of the best predictor of progression
      and irreversitiblity of preneoplastic bronchial lesion overwhelming morphological
      changes such as severe dysplasia. Restoration of wild type p53 function through
      p53 gene therapy, immunotherapy or modification of carboxy terminal end enable
      new therapeutic intervention. Finally, target genes and proteins situated on the
      downstream pathway of p53 transcription appears to be the most important factors
      of growth acceleration or even cell dissemination in lung cancer (Rb and its
      phosphorylation pathway, Bax-Bc12 balance and matrix degrading enzymes UPA and
      inhibitor PAI). Their constitutive deregulation could by-pass wild type p53
      functions. p53 pathway offers several targets for future gene therapy or
      modulation in the future in lung cancer.

PMID- 9769950
TI  - TP53 and hepatocellular carcinoma.
AB  - TP53 gene mutations occur in 30 to 55% hepatocellular carcinomas. Both the
      frequency and the type of p53 mutations in HCC vary according to geographical
      location of tumors. A specific mutation at codon 249 (AGG-->AGT) was found at
      high frequency in tumors from high aflatoxin-areas. TP53 mutations in other
      geographic locations are less frequent and scattered on the exons encoding the
      central region of the protein. TP53 mutations observed in hepatocellular
      carcinoma are accompanied by a loss of wild-type p53 function. Moreover, the p53
      249ser mutant appears to display a gain of function at some degree. In addition
      to p53 inactivation by gene mutation, there is growing evidence that the wild
      type p53 functions can be inactivated by the HBx protein of Hepatitis B Virus.
      The hepatocellular functions of wild-type p53 protein are not entirely known. The
      present data suggest that the DNA damaging agents induce p53-dependent cell cycle
      arrest or apoptosis in cell lines derived from normal liver or hepatocellular
      carcinoma. In contrast, the exposure of mice to genotoxic agents does not induce
      p53-dependent changes in normal adult liver. This could be due to the fact that
      the hepatocytes of the adult liver are quiescent cells.

PMID- 9769951
TI  - TP53 and oesophageal cancer.
AB  - Mutations of the tumor suppressor gene TP53 have been detected in tumor tissues
      of a large variety of human malignancies and contribute to the development,
      progression and probably the prognosis of the disease. The pattern of somatic
      mutations in the TP53 gene in human tumors most often consists of a point
      mutation in one allele accompanied by loss or rearrangement of the second allele.
      Esophageal cancer is one of the most commonly mutated cancer, p53 mutations
      having an incidence greater than 80% in squamous cell carcinoma. The profile of
      distribution of these mutations in the TP53 gene is of interest to establish
      correlation between the exposure to carcinogens responsible for DNA mutations.
      The other form of esophageal cancer, Barrett's esophageal is a good model to
      study the role of TP53 in mammalian tumorigenesis.

PMID- 9769952
TI  - [p53 and colorectal cancer].
AB  - Mutations of the p53 gene have been found in 380 of the 768 tumors (49.5%)
      included in the eight largest published series of colorectal cancer. Most point
      mutations of p53 change the conformation of the gene, and by stabilizing it make
      it detectable by immunohistochemistry. However, studies using both tests for p53
      mutations and immunohistochemical methods found that the results of these two
      approaches were concordant in only 68% of cases. Conflicting data have been
      reported regarding the prognostic significance of positive p53 staining. Presence
      of a mutation is generally believed to indicate a poor prognosis.

PMID- 9769953
TI  - p53 mutations in breast cancer: incidence and relations to tumor aggressiveness
      and evolution of the disease.
AB  - Breast cancer is a polymorphic disease and, until now, nodal invasion and steroid
      receptor levels remain the most powerful and widely used prognostic indicators.
      Molecular oncology has proven the importance of somatic genetic events in cancer
      genesis and evolution. In breast cancer a number of genetic aberrations have been
      proposed to bear impact on disease outcome. Greatest significance has been
      associated to ERBB2 amplification and overexpression. More recently p53 mutations
      have been suggested to bear meaning in terms of cancer evolution. We discuss here
      the molecular epidemiology of p53 mutations in human breast tumors and the
      clinico-pathological significance that can be associated to them.

PMID- 9769954
TI  - [p53 and prognosis of urothelial bladder tumors].
AB  - Transitional cell carcinoma of the bladder is heterogeneous and unpredictable.
      Tumor with similar clinicopathological parameters display different progression
      patterns. There is a need for a better management of these lesions, adapting the
      therapeutic load to tumor aggressiveness. Among various molecular abnormalities
      associated with tumor progression, analysis of p53 gene and/or p53 gene product,
      appears as a critical event. p53 mutation is observed in 34% of cases. Nuclear
      overexpression of p53 protein by mean of immunohistochemistry on tissue specimens
      and p53 gene mutations detectable on bladder washings may in the future implement
      histopathological and cytological analysis on routine preparations. Methods of
      standardisation and comparison between markers, are necessary in order to plan
      prospectives studies. These data strongly suggest that p53 gene and gene product
      alterations may be used as a clinically relevant tumor marker for bladder cancer.

PMID- 9769956
TI  - [Rationale for the use of corticoids in lung diseases].

PMID- 9769955
TI  - [p53 and hematologic malignancies].
AB  - Alterations in the p53 gene are less common in hematological malignancies (10 to
      15%) than in solid tumors, and usually consist in point mutations, which can be
      readily detected using SSCP or ICC. In most cases (except in non-Hodgkin's
      lymphoma) there is a close correlation between point mutations and a positive
      ICC. In myelodysplastic syndromes, acute myeloid leukemia, chronic myeloid
      leukemia, and chronic lymphoid leukemia, point mutations affecting one allele are
      accompanied with deletion of the other allele. The complete absence of the p53
      gene in these conditions probably explains the poor prognosis and resistance to
      chemotherapy in these patients. In contrast, in the L3 form of acute lymphoid
      leukemia and Burkitt's non-Hodgkin's lymphoma, punctual mutations are common
      (30%) and rarely accompanied with deletion of 17p. These data confirm the key
      role of p53 in the induction of apoptosis after chemotherapy and support the need
      for developing tools for transferring the p53 gene into malignant cells with the
      goal of restoring chemosensitivity.

PMID- 9769957
TI  - [Use of corticoids in acute lung diseases and long-lasting lung diseases].

PMID- 9769958
TI  - [Corticoids and lung diseases: conclusions, synthesis and perspectives].

PMID- 9769959
TI  - [Rationale for the use of corticoids in bronchial diseases].

PMID- 9769960
TI  - [Use of corticoids in acute bronchitis in the healthy subject and in COPD
      exacerbation].

PMID- 9769962
TI  - [Corticoids and bronchial diseases: conclusions, synthesis and perspectives].

PMID- 9769961
TI  - [Use of corticoids in chronic bronchial suppuration].

PMID- 9769963
TI  - [Rationale of infective risk of corticoids].

PMID- 9769964
TI  - [Corticoids and infective risk: point of view of the internist].

PMID- 9769965
TI  - [Corticoids and infectious risk: point of view of the pneumologist].

PMID- 9769966
TI  - [Corticoids and infection risk: conclusions, synthesis and perspectives].

PMID- 9769967
TI  - [Natural history of bronchial disease: asthma].

PMID- 9769968
TI  - [Natural history of bronchial disease: COPD].

PMID- 9769969
TI  - [Role of NO in asthma].

PMID- 9769970
TI  - [Genetic polymorphism of adrenergic beta 2 receptors].

PMID- 9769971
TI  - [Pharmacology of inhaled corticosteroids: new data and therapeutic implications].

PMID- 9769972
TI  - [Inhalation systems].

PMID- 9769973
TI  - [Evaluation of a clinical case of childhood asthma].

PMID- 9769975
TI  - [Role of nebulizers in asthma].

PMID- 9769974
TI  - [Mild asthma: new therapeutic approaches].

PMID- 9769976
TI  - [Role of nebulization in chronic obstructive lung diseases].

PMID- 9769977
TI  - [Bronchial inflammation in mucoviscidosis].

PMID- 9769978
TI  - [The Revue de Pneumologie Clinique and continuing medical education].

PMID- 9769979
TI  - [Strategies for the use of anti-retroviral agents in HIV infection (1997).
      Extracts from the 4th Dormont Report].

PMID- 9769980
TI  - [Respiratory variant of constrictive pericarditis. Report of 4 cases].
AB  - Constrictive pericarditis was diagnosed in four patients who presented
      respiratory impairment and pleural effusion, associated with right ventricular
      failure in two. The cause was probable tuberculosis in two cases, post
      irradiation lesions in one and unknown in one. The diagnosis was suspected due to
      the normal heart volume and pathological electrocardiogram as well as the
      computed tomographic findings demonstrating pericardial morphology. Right
      catheterism confirmed the diagnosis: increased right ventricular telediastolic
      pressure with a dip plateau and equivalent pressures in the right atrium and
      ventricle. Early diagnosis allowed pericardectomy in two cases. In one case, the
      subacute epicardopericarditis regressed with corticosteroids and antituberculosis
      therapy.

PMID- 9769981
TI  - [Broncho-pulmonary cancer associated with pulmonary tuberculosis. Report of 4
      cases].
AB  - The association between bronchopulmonary carcinoma and pulmonary tuberculosis
      would not be fortuitous but related to increased susceptibility to opportunistic
      infections and tuberculosis in cancer patients. We present four cases
      demonstrating the gravity of the situation and the difficulties encountered in
      diagnosis and treatment. Diagnosis of tuberculosis in patients with
      bronchopulmonary carcinoma requires pathological evidence from histology biopsies
      or bacteriology samples. The diagnosis is further complicated in early stage
      neoplasms. In case of tuberculosis, surgical treatment of bronchopulmonary
      carcinoma may have to be postponed or even contraindicated. Inversely,
      chemotherapy and radiotherapy may favor extension of the tuberculosis.

PMID- 9769982
TI  - [Late relapse of sarcoidosis. Report of 3 cases].
AB  - We report patients who were treated with corticosteroids for sarcoidosis and
      developed recurrent disease after 9 and 28 years of remission. The clinical
      latency, the type III radiographic aspect different from the initial presentation
      and the spontaneous course with periods of partial or total remission are
      characteristic of these late relapses. Clinicians should be aware of this
      uncommon clinical course and monitor cured cases for prolonged periods.

PMID- 9769983
TI  - [Cystic opacity of the posterior mediastinum].
AB  - A patient with atypical clinical signs had a thoracic schwannoma in the left
      paravertebral gutter. Rigorous analysis of the standard x-rays, computed
      tomography examination and magnetic resonance imaging gave the diagnosis and
      guided surgical resection. The pathology report confirmed the imaging findings.

PMID- 9769984
TI  - [Two new cases of autonomous ectopic goiter].
AB  - We observed two cases of autonomous intrathoracic goiter in patients with no past
      history of thyroidectomy. After resection, the surgical specimens confirmed the
      non-malignant nature of the goiter. We discuss the literature on management of
      autonomous intrathoracic goiter.

PMID- 9769985
TI  - [Pulmonary cavitated opacity in immunocompromised patient].
AB  - Lung abscesses are uncommon in legionellosis and usually are observed in
      immunocompromised patients. The radiographic presentation may lead to
      misdiagnosis and subsequently to increased mortality.

PMID- 9769986
TI  - [Restrictive myocardiopathy and pulmonary Raynaud's syndrome].
AB  - Idiopathic restrictive myocardiopathy is an uncommon condition. The differential
      diagnosis with constrictive pericarditis may require endomyocardial biopsy or
      surgical exploration. The prognosis of idiopathic restrictive myocardiopathy
      reported in the literature is to the order of several years. In this case the
      association with pulmonary Raynaud syndrome appears to be fortuitous and has not
      been previously reported.

PMID- 9769987
TI  - [Surgical volume reduction in emphysema: arguments in favor of restrictive
      indications].

PMID- 9769988
TI  - [Surgical lung volume reduction: are we moving towards extended indications?].

PMID- 9769990
TI  - [Liability of the pneumonologist. Recent medical civil legislation].
AB  - The clinician engages his penal, private and administrative responsibilities
      whenever he performs a medical act. Common law applies for private practice, as
      is the case of most pneumologists. Actually, there is little common law
      jurisprudence directly concerning pneumological situations. We present here the
      current trends and recent decisions made by judges faced with cases engaging
      physician's responsibilities.

PMID- 9769989
TI  - [Treatment of the paraneoplastic Lambert-Eaton syndrome].
AB  - The Lambert-Eaton syndrome is an autoimmune disease affecting the presynapse of
      the neuromuscular junction. Proximal muscle fatigue of the limbs is improved by
      repeated maximal voluntary contractions. Generally, patients present hypo or
      areflexia and frequently a dry mouth syndrome. In 50% of the cases, the Lambert
      Eaton syndrome is associated with small-cell bronchogenic carcinoma. The
      different treatments proposed in the literature for Lambert-Eaton paraneoplastic
      syndrome focus on treatment of the primary tumor. Symptomatic treatment of the
      junctional disorder are based on cholinergic drugs, immunosuppression and
      immunomodulation, useful in case of unsuccessful antineoplastic therapy.

PMID- 9769991
TI  - [Significance of systematic endoscopic decannulation. Retrospective study on
      intensive care patients].
AB  - We performed a retrospective study in 42 consecutive tracheotomy patients
      hospitalized in an intensive care unit. Endoscopy was used systematically to
      assess all patients at decanulation and whenever symptoms suggested possible
      tracheal granuloma. Nine tracheal granulomas were evidenced. There was no
      significant association between presence of a granuloma and patient status: age,
      underlying chronic respiratory failure, or tracheobronchial infection. In initial
      stages, tracheal granulomas usually have little clinical expression. Difficulty
      in weaning from ventilatory assistance is generally the main sign. The long-term
      course after decanulation can progress to major respiratory disorders due to
      tracheal stenosis. We emphasize the importance of systematic endoscopy at
      decanulation to recognize existing granulomas early when local treatment remains
      simple (usually laser vaporization).

PMID- 9769992
TI  - [Unusual lung mycosis: Penicillium++ marneffei infection].
AB  - We report an uncommon radiographic finding which led to the diagnosis of
      Penicillium marneffei pulmonary mycosis in an HIV positive woman. The patient who
      lived in France had travelled several times to her native country. Thailand,
      prior to the development of fever, weight loss, skin lesions with a macular
      aspect around the umbilicus. The chest x-ray demonstrated non-excavated round
      opacities. Penicillium marneffei was isolated from alveolar lavage fluid and
      blood samples. This rare fungus is usually found in immunodepressed subjects,
      especially HIV+ patients (CD4 < 50) should be suspected in subjects who have
      travelled to endemic zones (Southeast Asia). Penicillium marneffei is considered
      as a criteria for AIDS. P. marneffei is the only dimorphic member of the
      Penicillium genus and has a particular affinity for the reticuloendothelial
      system. Clinical manifestations vary, usually with skin lesions. Mycology
      diagnosis is usually made on blood samples as well as alveolar lavage or pleural
      fluids. Antifungals (amphotericin B. itraconazole, ketoconazole) are generally
      effective but the risk of relapse underlines the importance of secondary
      prophylaxis in immunodepressed subjects.

PMID- 9769993
TI  - [Phrenic nerve malignant schwannoma: an exceptional diagnosis].
AB  - We report a case of malignant schwannoma of left phrenic nerve in a 65-year-old
      man. This uncommon diagnosis was suggested by radiological features and confirmed
      by histological findings on a needle biopsy and surgery specimens. We discuss
      management, follow-up and prognosis of malignant schwannomas.

PMID- 9769994
TI  - [Unusual bronchial tumor...].
AB  - We report a case of atelectasis of the upper right lobe which did not respond to
      antibiotics. A third bronchial endoscopy with bronchoalveolar lavage was required
      to make the diagnosis of endobronchial nocardiasis. Search for extension revealed
      a brain localization. Search for immune deficiency only revealed calcification of
      the bronchial mucosa in the area of the nocardiasis.

PMID- 9769995
TI  - [Difficult catheterization].
AB  - We report a case of a spontaneously ruptured implantable-chamber catheter which
      migrated to the right atrium. Removal by interventional radiology techniques is
      the treatment of choice for this type of complication.

PMID- 9769996
TI  - [Maintenance chemotherapy in small cell lung cancer: reasons for not using it].
AB  - There is no consensus as the optimal duration for treatment in patients with
      small-cell lung cancer. In routine practice, 6 cycles of chemotherapy are usually
      delivered, but the rate of recurrence after achieving objective response has
      incited interest in several trials aimed at evaluating the effect of prolonged
      "maintenance" chemotherapy. Such prolonged regimens may use the same drugs as
      used in the induction protocol or call upon new drugs. No conclusion can be drawn
      from the 14 randomized studies conducted to date because of differences in the
      randomized populations as well as the nature of the treatments tested. Among 9
      trials using a maintenance regimen with the same drugs as the induction protocol,
      there has been no significant difference in long-term survival. One study even
      found a lower 2-year survival with maintenance therapy. Among 5 trials where the
      maintenance protocol used drugs different from the induction protocol, survival
      rate favored maintenance chemotherapy in only 1. Most authors have observed a
      significant deterioration in quality of life in patients given maintenance
      chemotherapy, in addition to a number of deaths due to drug toxicity. Patient
      recruitment had to be interrupted in one study. The percentage of patients who
      received the entire maintenance protocol was also very low in many trials (20%).
      There may exit a theoretical advantage to giving maintenance chemotherapy, but
      does it counterbalance the risk of late complications? An increased risk of a
      second cancer has been demonstrated in patients given more than 6 cycles in the
      National Registry of long-term survival. Given the current state of our
      knowledge, it would not appear reasonable to propose maintenance chemotherapy for
      patients with small-cell lung cancer outside controlled clinical trial protocols.

PMID- 9769997
TI  - [Maintenance chemotherapy in the treatment of small cell lung cancer: the
      advocate's view].
AB  - The role of maintenance chemotherapy in the treatment of small cell lung cancer
      remains controversial. We have collected the arguments in favor of that approach
      by performing a quantitative and qualitative overview of the studies published on
      this topic in the French and English literatures since 1980. On the thirteen
      prospective randomized trials reported, six demonstrated a significant survival
      advantage in favor of maintenance, no difference was observed in 6 and 1 study
      had a significant survival advantage for no maintenance. Due to the heterogeneity
      of the study designs and to the lack of published data, no meta-analysis could be
      performed. A qualitative overview of the different trials showed that the quality
      scores of the positive trials was similar to the negative ones, allowing us to
      conclude that they could be considered at the same level. No negative trial with
      a similar design can be opposed to each particular positive trial that is thus
      not conterbalanced. Moreover the trials not in favor of maintenance could be
      falsely negative by a lack of power, the publications mentioning no statistical
      consideration. There are thus a series of arguments in favor of maintenance
      chemotherapy for small-cell lung cancer, which require to be confirmed by
      randomised trials of adequate quality.

PMID- 9769998
TI  - [Aerosols: a re-emerging treatment].
AB  - Aerosol drug delivery is widely used by patients with asthma and chronic
      bronchial obstruction for beta-2 agonists and anticholinergic drugs. More
      recently, inhaled steroid sprays have also been introduced. The efficacy of easy
      to use aerosol sprays is well proven and has become an important administration
      route. Different models of metered dose inhalers with gas propellants or dry
      powder devices help improve patients compliance. Nebulizers can be used in
      particular situations. Aerosol administration is proposed for anti-infectious
      agents and for rhDNase in cystic fibrosis. Aerosol delivery of nucleotides and
      antiproteases are currently under evaluation. Gene therapy can also benefit from
      the aerosol route which may be proposed in the near future for many different
      types of systemic treatments. Possible drugs include cyclosporin for lung grafts,
      prostacyclin for primary pulmonary hypertension, insulin for diabetes or morphine
      in certain types of dyspnea.

PMID- 9770000
TI  - [Does D-dimer determination allow the exclusion of pulmonary embolism?].
AB  - The presence of D-dimers in the serum reflects fibrin formation and lysis. If the
      serum D-dimer level is lower than a threshold level which depends on the assay
      technique (usually 500 micrograms/l), pulmonary embolism can be excluded with a
      predictive value of 95%. This makes D-dimer assay an ideal screening tool for
      ambulatory patients with suspected pulmonary embolism. Screening costs can be
      reduced in about one-third of the cases as other tests are not required. For
      routine practice, only ELISA tests have been validated for this indication, the
      sensitivity of latex tests being too low. D-dimer assay would be of little
      benefit for patients hospitalized for more than 24 for reasons other than
      suspected pulmonary embolism as specificity is very low in this population.

PMID- 9769999
TI  - [Bronchiolitis obliterans with organizing pneumonia. Retrospective study of 19
      cases].
AB  - We report a series of 19 cases of bronchiolitis obliterans with organized
      pneumonitis (BOOP) observed in two pneumology units at the Strasbourg University
      Hospital between July 1987 and June 1997. Mean patient age was 60 years. Clinical
      features included dry cough, exercise-induced dyspnea, and a flu-like syndrome in
      three-quarters of the cases. Standard chest x-ray showed a diffuse non-systemized
      alveolar syndrome with a air bronchogram in 18 cases and an interstitial syndrome
      in one-third of the cases. computed tomography of the thorax visualized bronchial
      dilatations by traction of the alveolar syndrome in one-third of the cases.
      Pulmonary function tests showed moderate restriction. Lymphocytes predominated in
      bronchio-alveolar lavage fluid. Pathology examination of surgical lung specimens
      (5 cases), transbronchial biopsies (5 cases) and scan-guided transparietal
      punctures (4 cases) provided the diagnosis. In 5 cases the diagnosis was based on
      the radiological and clinical presentation and favorable course on corticosteroid
      therapy. Recurrence was observed at corticosteroid withdrawal or dose reduction
      in 7 cases. In this series, bronchiolitis obliterans with organized pneumonitis
      was probably secondary to rheumatoid arthritis (1 case), breast radiotherapy (3
      cases), and drugs (amiodarone: 1 case: sotalol: 2 cases: betaxolol: 1 case). An
      association with betaxolol has not been previously reported in the literature.

PMID- 9770001
TI  - [Diffuse panbronchiolitis in an elderly patient. A case report].
AB  - Diffuse panbronchiolitis is a chronic obstructive bronchopulmonary disease
      generally observed in adults. We report a case of diffuse panbronchiolitis in a
      86-year-old woman. Respiratory failure led to death after a 6-year clinical
      course. Pathology examination of autopsy specimens confirmed the diagnosis.

PMID- 9770002
TI  - [Acute pericarditis of unusual etiology].
AB  - Extrapulmonary manifestations of Legionella pneumophilia infection are
      infrequent. Cardiac involvement can occur. We observed an unusual case which led
      to acute pericarditis and reviewed the literature on cardiac involvement,
      particularly pericarditis, in patients which legionellosis.

PMID- 9770003
TI  - [Hypoxemic acute diffuse pneumopathy in therapeutic aplasia for acute myeloid
      leukemia].

PMID- 9770004
TI  - [Unusual cause of necrotized subacute pneumopathy].
AB  - We report a case of Streptococcus milleri (S. intermedius) pulmonary infection in
      a 66-year-old woman. The patient was a heavy smoker and had diabetes. The
      diagnosis was proven by transparietal pulmonary aspiration.

PMID- 9770005
TI  - [5HT-moduline an new peptide specifically interactive with the serotonergic
      system: physiopathologic implications].
AB  - 5-HT1B receptors play a specific role as one of the many receptors regulating
      serotonergic activity. This endogenous peptide was recently isolated and
      characterized. Specific interaction has been demonstrated. 5-HT-moduline appears
      to be implicated in central nervous system response to various stimuli,
      particularly stress. It might play an important role in adaptation/inadaptation
      mechanisms (stress, anxiety, depression).

PMID- 9770006
TI  - [Nitric oxide: a different kind of gas].
AB  - Nitric oxide (NO), the first gas to obtain temporary approval for use in
      medicine, is regulated in private and public health care facilities by the
      supply, prescription and dispensing rules applied for drugs with special
      modalities controlling its administration. This apparently simple gas which
      diffuses easily from one cell to another is actually very complex in its form and
      reactivity, making it an unconventional messenger. The life time of a molecule is
      very short. NO is synthesized and released continuously. Its direct or mediated
      vasodilator effect has led to four temporary approval rulings validated again in
      1997 by the national health authorities.

PMID- 9770007
TI  - [Stereoselective synthesis of biologically active macrolides. Total synthesis of
      tylosine].

PMID- 9770008
TI  - [SCA 40 and derivatives: new bronchodilators in an imidazo(1,2-a)pyrazine
      series].
AB  - Asthma is a complex disease characterised by bronchoconstriction and airways
      inflammation. Recent advances in medicinal chemistry will surely lead to a better
      reappraisal of therapeutic strategies. 8-(Methylamino)imidazo(1,2-a)pyrazines
      with substitution either on position 2 or 3 powerful relaxing agents in vitro as
      well as in vivo in animals. 6-Bromo-8-(methylamino)imidazo[1,2-a]pyrazine- 2
      carbonitrile, SCA40, is a new and potent bronchodilator. Chemical synthesis of
      such a series of derivatives involves a condensation reaction with formation of
      the imidazole ring and/or diverse electrophilic substitutions. Chemical
      reactivity of the heterocycle can be modulated by introduction on position 8 of
      electrodonating groups that highly favor electrophilic substitution on position
      3. Interestingly, lithiation studies on the heterocycle exhibit regioselectivity,
      leading either to an halogen exchange when position 3 is occupied by a bromine
      atom or an ortho-directed metalation in accord with the presence of an halogen on
      position 6.

PMID- 9770009
TI  - [Synthesis and pharmacologic evaluation of 3-(2- and 4-pyridinyl)indane-1,3
      diones and structural analogues with potential anti-inflammatory and
      antineoplastic activity].
AB  - Our on going work in the series of enamido-diketones issued from 2-azaarylindane
      1,3-diones led us to synthesize and experiment N and C2-substituted derivatives
      of 2-(2 and 4-pyridinyl)indane-1,3-diones as well as of structurally related
      compounds resulting from the replacement of pyridine by quinoline and
      benzimidazole. Pharmacological evaluation of their anti-inflammatory activity (by
      inhibition of carrageenan foot edema) and their anticoagulant activity (by
      prothombin assay) led to the conclusion of the possibility of achieving a
      selective anti-inflammatory effect. It has been previously established that
      anticoagulants are liable to exert a protective effect in the development of
      cancer metastasis. Nevertheless none of the six experimented 2-(pyridin-2
      yl)indane-1,3-diones extended survival time of mice treated by P388 lymphocytic
      leukemia.

PMID- 9770010
TI  - [Synthesis and pharmacologic study of 1,5-benzodiazepine-2,4-diones and their
      alkyl derivatives].
AB  - From the pharmacodynamic studies of 1,5-benzodiazepin-2,4-diones and alkyl
      derivatives prepared in our laboratories, we can conclude that these products are
      not toxic at therapeutic dosage. They have sedative, myorelaxant and anxiolytic
      actions. The two products alkylated by allyl bromide have also hypnotic, sedative
      and anticonvulsant properties.

PMID- 9770011
TI  - [Synthesis and pharmacologic study of 1,5-benzodiazepine-2,4-dithiones and their
      alkyl derivatives].
AB  - From the pharmacodynamic studies of 1,5-benzodiazepine-2,4-dithiones and alkyl
      derivatives, we can conclude that these products are not toxic at therapeutic
      dosage. They have sedative, myorelaxant and anxiolytic actions.

PMID- 9770012
TI  - [Antimicrobial activity of some derivatives of pyrimidine].
AB  - In this paper the authors present the antimicrobial and antifungical tests of
      some new 3-methylpyrimidine compounds. The test was performed using the
      diffusimetric method with rustlessteel cylinders based on the diffusion of the
      tested substances on the gelose surface. The comparative analysis of the obtained
      data leads to the following conclusions concerning the relation between structure
      and biological activity in the pyrimidine series: 1. The pyrimidinium ylides are
      less active comparatively with the corresponding salts. That means that the
      zwitter ionic structure did not favour the activity. 2. Comparative with the
      corresponding pyridazine(1,2-diazine) derivatives, the pyrimidine(1,3-diazine)
      compounds are more active. The increase of activity of the pyrimidine compounds
      could be attributed of the influence of the pyrimidine ring. 3. The most active
      pyrimidine compound which is tested is that one in which radical R is an amide
      group. 4. In the case when the radical R is a phenyl ring, the substitute from
      para position of benzoylic radical does not appear decisive towards activity,
      these affecting especially the selectivity.

PMID- 9770013
TI  - [The antimicrobial properties of some chewing sticks from Togo].
AB  - Eight togolese species for chewing sticks are tested on germs. Most of them have
      antimicrobial properties.

PMID- 9770014
TI  - [Multiple demands for assistance from pharmacists. Analysis and evaluation].
AB  - The pharmacist is a member of the health care community readily accessible to the
      public. Beyond his/her normal attributes, the pharmacist is called upon to offer
      assistance, sometimes in an emergency setting, or, more generally, in situations
      requiring compassion and support. We conducted a study of 349 observations of
      requests for assistance and analyzed this free often discrete but highly
      important service offered daily by pharmacists. For each experience presented,
      the intervention was conducted by the pharmacist and required a considerable
      amount of effort and time. As for all professional activities, the pharmacist
      engaged his/her own responsibility. Four main categories of interventions were
      observed. Several "colorful" examples are presented, demonstrating that
      assistance provided by the pharmacist is an important asset of the profession
      which is widely appreciated and used by the public.

PMID- 9770015
TI  - [Eosinophils: protection or pathology: a cell with two personalities].
AB  - Expression of various membrane receptors on human eosinophils for immunoglobulin,
      complement, certain cytokines and chemotaxis factors, and adherence molecules as
      well as CD4 and class II major histocompatibility complex antigens has led to a
      reconsideration of the role of the eosinophil in the immune response. Eosinophils
      are able to present antigen and become infected by HIV. Eosinophils are not to
      only source of cytotoxic and proinflammatory mediators but can also release
      different cytokines and growth factors including their own differentiation
      factors. The recent demonstration that eosinophils can express IgE-binding
      molecules belonging to different multigenic families as well as two different IgA
      receptors which participate equally to the protective and to the pathological
      inflammatory responses reinforces the concept of a dual functionality for the
      eosinophil.

PMID- 9770016
TI  - [Gaucher's disease and enzyme replacement therapy].
AB  - Gaucher disease is an autosomal recessive genetic disorder characterized by a
      deficiency in the glucocerebrosidase enzyme. Glucocerebroside then accumulates in
      macrophages (Gaucher cells), causing anemia, thrombocytopenia, organomegaly and
      major bone problems. Discovery of the enzyme deficiency by Brady in 1964, and
      subsequent extraction and partial deglycosylation of the native enzyme led to a
      treatment. 1,600 people out of 5,000 possible worldwide patients benefit from
      this drug. The 70 French treated patients (out of an estimated 200) show
      remarkable improvement.

PMID- 9770017
TI  - Acute phase proteins: clinical and laboratory diagnosis. A review.
AB  - Acute phase proteins play an important role in clinical laboratory diagnosis,
      especially after recent development of quantitation methods. Turbidimetry and
      nephelometry, spectrophotometric procedures based on the quantitation of
      scattered and reflected light, permit laboratory analyses of higher precision,
      sensitivity and specificity compared to previously employed methods.

PMID- 9770018
TI  - [Thorium a radioactive element in current use: physical-chemical properties and
      biological processing].
AB  - The radioactive properties and physicochemistry of thorium were studied and
      correlations drawn between thorium and element sof the titanium group,
      lanthanides and plutonium. It appears that the behavior of Th4+ and Pu4+ are
      similar, particularly their distribution pattern on bone surfaces. Chelating
      agents are reviewed and the structure of metal chelates indicated.

PMID- 9770019
TI  - [Thorium: analysis and dosimetry of thorium welding electrodes].
AB  - The use of thoriated tungsten electrodes may be at the origin of a potential
      hazard for the personnel involved in the use of electrodes, as well as the
      general population. To assess this hazard, the electrode radioactivity
      measurements by alpha and beta counting has been conducted. The radioelements
      were identified by alpha and gamma spectromety. It appeared that there was a
      radioactive disequilibrium between thorium-232 (Th-232) and it daughters atoms.
      Additionally, some thorium 230 (Th-230) belonging to the uranium chain, was
      present. The chemical separation and the milling processing had affected the
      radioactive composition and the thorium in the electrodes, doesn't exactly
      corresponds to natural thorium. Radiation doses were also assessed: film and
      photoluminescence dosimetry were undertaken. Finally smears method showed a alpha
      removable area contamination. Even if the hazard is weak. As a matter of fact, it
      must not be neglected because it was complex, for the thorium was always
      accompanied by Th-232 progeny, alpha emitters but also beta and gamma emitters.

PMID- 9770021
TI  - [The pharmacist-nutritionist: myth or necessity?].
AB  - Nutrition has taken on great importance in the health considerations of the
      general population. To meet expectations many fields have been called to
      contribute. With his multi-disciplined training the Pharmacist can and should
      have an important role to play. Upstream, the agro-food industry has many
      opportunities to offer. Our knowledge of Genetics, Molecular Biology and Botany
      can be a great advantage. Nutriceuticals are at the interface of nutrition and
      medicine. They concerns foods which have preventative or curative properties for
      certain illnesses. Are we going to be able to integrate into this new concept?
      Administered in pharmacological doses certain nutriments are indeed drugs. The
      Pharmacist should have a better training in Nutrition in order to be able to do
      his job properly. In hospitals the Pharmacist dispenses and sometimes prepares
      solutions for parenteral nutrition, while the biologist participates in
      denutrition diagnosis.

PMID- 9770020
TI  - [Vascular contrast agents. Definition and potential applications].
AB  - Blood pool agents are characterized by a biodistribution limited to the vascular
      space after intravenous injection. This is different from uroangiographic agents
      in CT Scanner or Gd chelates in MRI which are markers for the intra and
      extravascular space. This unique property is potentially useful for diagnostic
      applications such as ischemic diseases (myocardial or cerebral perfusion
      defects), vascular diseases and diagnostic or follow-up of endothelial
      permeability disorders (diabetic patients, tumors...).

PMID- 9770022
TI  - [Management of medico-surgical instruments in the dental office].

PMID- 9770023
TI  - [Society before and after the introduction of psychotropic drugs in therapeutic
      use].
AB  - Despite unavoidable subjectivity, it would appear that the use of antidepressive,
      anxiolytic and hypnotic agents has increased over the past years, although
      consumption of benzodiazepines appears to have stabilized recently. It is
      generally accepted that there has been a trend to medicalization of mainly social
      problems. The following factors have been considered: type of the person's
      request, with an often dominant role related to assisted behavior; medical
      responses, frequently marked by a preferential if not exclusive reliance on the
      chemical compound; financial limitations on national medical expenses, quite
      probably an indirect cause of changing status and role of medicine distorting the
      therapeutic relationships; marketing phenomena involving major economic
      challenges. Faced with this conflictual situation, we must try to maintain the
      physician's freedom to practice for patient benefit.

PMID- 9770024
TI  - [Behavioral and neurochemical methods in research on new psychotropics].
AB  - Since the discovery of the antipsychotic effects of chlorpromazine by the French
      psychiatrists DELAY and DENIKER in 1952, preclinical pharmacologists have
      proposed several laboratory tests, that have been used to demonstrate the
      potential activity of drugs in the treatment of mental disorders including
      schizophrenia, depressive illness and anxiety. Tests are divided into behavioural
      tests and neurochemical tests. Electrophysiology tests are not considered in this
      paper. Concerning schizophrenia, although there is no valid model, behavioural
      tests presently used are: antagonism against various responses induced by
      dopamine receptor agonists, inhibition of conditioned behaviours, latent
      inhibition, startle reaction, models related to the neurodevelopmental
      hypothesis. For antidepressant activity, models are based on antagonism of
      various effects of reserpine. More anthropomorphic models involve helplessness
      behaviours, social isolation, changes induced by limbic system lesions.
      Biochemical investigations mainly involve in vitro and in vivo tests: study of
      changes in the metabolism of neurotransmitters using microdialysis and other
      procedures, interaction with receptor subtypes. As a result of advances in
      molecular biology, other tools are now emerging, but classical tests remain
      useful.

PMID- 9770026
TI  - [The consumption of psychotropics in France and some european countries].
AB  - The consumption in France of psychotropic drugs, of all classes, except for
      neuroleptics, is great, even very great, and largely superior to that observed in
      neighbouring European countries such as Germany, Spain, Italy and the United
      Kingdom. With regard to hypnotics and anxiolytics, 5 to 7 per cent of the French
      adult population consumes them regularly. The percentages rise with age, among
      females, and with the presence of unfavourable medical-social conditions. The
      consumption of this class of therapeutic drugs has remained stable for about ten
      years. The consumption of antidepressants regularly grows at a rate of about 5
      per cent per year, essentially linked to the consumption of serotonin-recapture
      inhibitors and especially fluoxetine, currently prescribed by general
      practitioners in about 60 per cent of cases. The factors responsible for the
      strong French consumption of psychotropic drugs and the divergences with our
      European neighbours are complex, numerous, and poorly analysed for lack of valid
      comparative studies. Better prescribing practices require specific initial and
      continuous training to take into account the realities of everyday medical
      practice.

PMID- 9770025
TI  - [From gene to behavior, a new method for elaboration of new psychotropic agents].
AB  - Traditionally, the screening of new neuropsychotropic agents started from the
      observation of behavioural effects resulting from the administration of a new
      chemical. Then, one tried to determine its mechanism of action. Since about a
      decade the way for discovering psychotropic agents tends to be inverse. It starts
      from the characterization of genes and investigates on their expression products
      which are new biological targets. Ligands for these targets are developed and
      then the effects resulting from their administration are considered. In this new
      strategy, we will consider the cloning of genes and their expression in cultured
      cells; the knock out of these genes by homologous recombinaison; the extinction
      of gene expression by antisense oligodeoxynucleotides; the concentration of
      behavioural phenotypes by selective breeding.

PMID- 9770028
TI  - [Psychotropic drugs and primary care].
AB  - Nowadays psychiatrists and general practitioners are confronted with two
      realities which seem to be conflicting: psychotropic drugs are too largely
      prescribed while many depressed patients are not treated adequately. Any approach
      based upon clinical and/or pharmacological criteria is likely to oversimplify the
      medical practice in as much it generates too many clinical entities and shrinks
      drugs-induced effects to responses of isolated target. The specificity of any
      symptoms has to be evaluated within the limits of other associated symptoms and
      patient's personality. The treatment has to be carried out on a joint basis; the
      patient who has to be informed and the doctor who is also the patient's adviser.
      Patients' demand is changing, looking for permanent improvement of their well
      being as well as improvement of their performances. The answer is clearly
      complicated and needs more knowledges and also deep concern on mankind.

PMID- 9770027
TI  - [Psychotropic drugs and behavior].
AB  - Behavioral modifications induced by psychotropic drugs result primarily from
      their pharmacological properties. According to classification of psychotropic
      drugs, sedative compounds contrast with psychostimulating medications.
      Behavioural effects of psychotropic drugs depend on dosing, subject's status
      (patient or healthy volunteer), acute or chronic administration, and environment.
      Some psychotropic compounds, particularly sedative drugs, decrease the level of
      mental alertness and cognitive functioning. But those deleterious effects tend to
      disappear during the course of a repeated administration. Some psychotropic
      drugs, especially benzodiazepines, induce a tolerance effect, eventually a
      psychic or a physiological dependence state evidenced by withdrawal reactions.
      Such similar dependence processes have been reported with other psychotropic
      drugs. Forensic problems have been attributed to some psychotropic compounds,
      like benzodiazepines: paradoxical aggressive reactions, psychomotor automatism.
      Psychotropic drugs usually can confer a positive effect on behaviour owing to
      their therapeutic action by the way of improving the illness and consequently the
      life of patients in the cases of depression, anxiety or schizophrenia.

PMID- 9770029
TI  - [Differentiating the activity of anticancer drugs: the role of transcription
      factors].
AB  - The understanding of the mechanisms responsible for the emergence and evolution
      of cancers has been in constant progress due to advances in molecular biology.
      Today it allows to conceive therapeutic alternatives to conventional cytotoxic
      chemotherapy. Among these, differentiation strategy, which aims at reinducing
      tumour cells towards a normal phenotype, has known a first clinical application
      with the use of retinoic acid in acute promyelocytic leukemias. Anthracyclines,
      traditionally employed in cytotoxic chemotherapy, present also a high potential
      of differentiation. Their mode of action takes place via the activation of
      transcription factors, which are proteins that are able to modulate the
      expression of genes by fixing to regulatory sequences of DNA. These observations
      therefore allow us to foresee a new pharmacology based on transcription factors
      for the treatment of cancers.

PMID- 9770030
TI  - [Evaluation and interest in new molecular markers in colon cancer].
AB  - The presence of colonic tumor cells in the circulation may predict colorectal
      carcinoma recurrence and metastases. We have developed a highly sensitive nested
      RT-PCR assay, with primers derived from the cytokeratin 20 (CK20) and the
      carcinoembryonic gene CGM2, to detect occult microdisseminated enterocytes in
      blood of colorectal cancer patients. Among 82 healthy controls analyzed, 40.2%
      (33/82) have a positive expression of CK20 mRNA which is not statistically
      different from the 45.5% (15/33) of positive results found in colon cancer
      patients. This sensitive method may detect non-tissue specific constitutive low
      level (illegitimate) expression of CK20 mRNA in peripheral nucleated blood cells
      (PNBC) of a significant number of healthy control as well as in a number of
      normal bone marrow. The low specificity of this assay therefore hampers its value
      to detect blood colon cancer dissemination. In 47 patients with colorectal
      carcinoma, CGM2 primers detected circulating enterocytes in 25 of them (53%). In
      disseminated Dukes' stage C disease patients, 17 out of 29 (59%) were found
      positive whereas in localized adenocarcinoma (Dukes's stage A and B), CGM2
      primers detected enterocytes in 44% suggesting that an hematogenous spillage of
      colonic cells may be a relatively early event in colon cancer. None of the
      patients suffering from benign colonic pathologies or from diverticulitis were
      found positive for this assay. The analysis of 56 healthy individuals without
      known colorectal cancer, of 20 non-colorectal cancer patients and of 6 normal
      bone marrows provide evidence that this assay is highly specific and may predict
      an hematogenous spread of colonic cells in patients with organ-confined disease.
      Nevertheless, the clinical significance of enterocyte detection and the potential
      applications of this molecular tool merit longer term follow-up.

PMID- 9770031
TI  - [The plasma antioxidant status and trace elements in patients with familial
      hypercholesterolemia treated with LDL-apheresis].
AB  - Oxidation of low density lipoprotein is involved in the pathogenesis of
      atherosclerosis. Epidemiological studies suggest a negative correlation between
      the occurrence of cardiovascular diseases and blood concentrations of lipophilic
      antioxidants such as vitamin A and E and beta-carotene. Trace elements such as
      selenium, zinc and copper are involved in the activity of antioxidant enzymes:
      glutathione peroxidase and superoxide dismutase. The aim of this work was to
      determine the antioxidant and trace elements status of patients with very severe
      hypercholesterolemia and who were treated by dextran sulphate low density
      lipoprotein apheresis, in comparison with two control populations: one
      constituted by normocholesterolemic subjects and the other by
      hypercholesterolemic patients before treatment. Our results showed that, as
      compared with normocholesterolemic subjects, patients treated by LDL-apheresis
      were not deficient in vitamin E, beta-carotene and copper but had low plasma
      levels of selenium, zinc and vitamin A. The low selenium and vitamin A levels
      were due to the treatment by LDL-apheresis by itself, while the
      hypercholesterolemia of these patients might have provoked the low plasma levels
      of zinc. This study pointed out the interest of a supplement of selenium, zinc
      and vitamin A in patients treated by LDL-apheresis.

PMID- 9770032
TI  - [Spongiform encephalopathies: a second chance for GABAergic agonists].
AB  - The risk of transmission of bovine spongiform encephalopathy (BSE) to humans and
      of a possible emergence, in the future, of an epidemic being seriously envisaged,
      a detection of the infection by the BSE prions is at present going well. On the
      other hand, recent neurochemical studies could suggest the triggering of an
      overstimulation of the brain GABAergic and glutamatergic systems after infection
      by the BSE prions. This overstimulation could, in the long-term (latency between
      the infection and the emergence of the clinical signs of the disease), lead to
      the destruction of the major inhibiting system (GABAergic) of the brain and the
      generalization of the neurotoxic processes. According to the above mentioned
      working hypothesis, it could be envisaged to use, immediately after the detection
      of the infection by the BSE prions, mixed GABAergic (A, B) agonists, selectively
      acting on the GABAergic autoreceptors and on the heteroreceptors situated on the
      glutamatergic terminals. Moreover these agonists could exhibit molecular
      characteristics (in terms of lipophilicity), which could operate in order to
      prevent the fixation of prions on the neuronal and astroglial membranes allowing
      their multiplication. According to the above mentioned criteria, mixed agonists
      Progabide and Gabalid or some GABA (B) agonists, with a relatively low affinity,
      could, actually, be the most interesting.

PMID- 9770033
TI  - [Diterpene and phenylpropanoid heteroside esters from Ballota nigra L].
AB  - A preliminary survey of the botanical characters of the species Ballota nigra and
      of its subspecies is reported. Phytochemical investigation of the flowered aerial
      parts led us to isolation and structural elucidation of one diterpene (13
      hydroxyballonigrinolide) and four phenylpropanoid glycosides reported for the
      first time from the genus Ballota: verbascoside, forsythoside B, arenarioside and
      ballotetroside. These compounds appear to be characteristic of this species and
      could be used for the standardization of the drug. Moreover, the four
      phenylpropanoid glycosides isolated could justify the use of Ballota nigra as a
      neurosedative drug.

PMID- 9770035
TI  - [Guidelines to good execution of analysis: some applications and developments.
      Laboratoire d'Analyses de Biologie Me'dicale Lecoeur].
AB  - The decree concerning the Guidelines for Good Execution of Analyses (GGEA)
      promulgated on December 4, 1994 entered into application on January 1, 1995. The
      definition and necessity for the GGEA is discussed in the first part of this
      article. Actually, the GGEA is a revolutionary change for biology laboratories
      which must now work within the framework of precise guidelines. This may raise
      certain problems for private laboratories. The goal of the GGEA is to assure good
      quality analyses and thus patient care. It is designed as a positive aid for the
      biologist. Thus after two years of application, it is time to improve the initial
      text taking into account experience in the field. In the future, the official
      authorities and leaders in the profession will have to choose between the GGEA
      and official approval.

PMID- 9770034
TI  - [Normalization of hedge mustard, Sisymbrium officinale L].
AB  - Dried flowering aerial parts of 11 harvested batches and 14 batches of commercial
      origin from Sisymbrium officinale L. were examined. The levels of principal
      constituents averaged respectively: total glucosinolates 0.63 and 0.94%,
      mucilages 13.5 and 10.9%, total itols 8.9 and 10.2%, total flavonoids 0.50 and
      0.56%. Specifications were discussed for a French Pharmacopoeial monography.

PMID- 9770036
TI  - [Development of normalization: antiseptics and disinfectants].

PMID- 9770037
TI  - [The otolaryngologist and Creutzfeldt-Jakob disease].
AB  - Is the ENT surgeon guilty of being a vector in Creutzfeldt-Jakob disease (CJD) in
      the past, present and future, with possible medico-legal implications, by virtue
      of his use of biomaterials and of his failure to sterilise surgical instruments
      adequately? Once the disease has been diagnosed, are there any implications for
      ENT? CJD is the most frequent clinical manifestation of the infectious subacute
      spongiform encephalopathies. It is invariably fatal within a few months, and at
      present there is no known treatment. Currently the diagnosis can be confirmed
      only by brain biopsy, but diagnostic tests are being developed. The causative
      agent belongs to the group of non-conventional transmissible agents, or prions,
      which are resistant to all conventional sterilisation methods. The illness has a
      long incubation period extending to several years, during which the abnormal
      prion protein (PPr), derived from a protein which is normally present,
      accumulates in the central nervous system. CJD is a rare condition, affecting
      less than one in a million of the population, and manifests itself in one of
      three distinct ways: sporadic, in 90% of cases, possibly due to a natural
      mutation of the gene responsible for formation of the protein, hereditary
      familial (5 to 10% of cases); and iatrogenic, transmitted by the implantation of
      biomaterials of human origin, which are the cases for which the ENT surgeon could
      be responsible, and which may affect any age group. The possible modes of ENT
      transmission have been identified. These could be the use of surgical material
      contaminated by a patient suffering from CJD, the use of human biomaterials
      whether dural homografts, ossicular homografts taken together with the donor
      dura, the use of blood products, or the use of biomaterials of bovine origin.
      Such materials have been used widely in the past without any observed increase in
      new CJD cases, but the incubation period of this disease is not well understood.
      A knowledge of the possible alternatives and of the new relations on the subject
      should allow us to improve the epidemiology of the condition, help the surgeon in
      his choice of materials, help in the diagnosis of the condition, and in avoiding
      its transmission by heeding new advice on sterilisation.

PMID- 9770038
TI  - [Maxillary actinomycosis and maxillary candidiasis in the immunocompetent
      patient].
AB  - Two distinct cases of maxillary actinomycosis and maxillary candidosis in
      immunocompetent hosts are reported; These infections are rare and similar to
      mycotic extramucosal non allergic sinusitis. Microbiology and microscopic
      examination are mandatory to prompt and successful management. Endoscopic
      endonasal surgery by middle meatotomy seems to be an adequate treatment for these
      particular entities.

PMID- 9770039
TI  - [Otolaryngological manifestations of sarcoidosis. Report of 10 cases and review
      of the literature].
AB  - Sarcoidosis is a systemic chronic granulomatous condition of unknown aetiology.
      Although the mediastino-pulmonary type is the commonest, the condition may affect
      the head and neck in a significant number of cases, obliging the practising ENT
      surgeon to be familiar with the condition. The diagnosis is made by a combination
      of clinical, biochemical, radiological and histopathological features. We present
      10 cases of sarcoidosis with exclusively cervico-facial features which have
      passed through the department between 1985 and 1996, including a typical nasal
      case with combined features, and a very rare pharyngeal case. The definitive
      diagnosis, always with histological confirmation, was sometimes made only after
      some delay, demonstrating the polymorphic nature of the clinical features, which
      are rarely pathognomonic. Special investigations, carried out virtually routinely
      once the diagnosis of ENT sarcoidosis was made, demonstrated only one case of
      associated pulmonary disease. Treatment was reserved for the symptomatic cases (4
      out of 10), and consisted of systemic steroids whose dose and duration was
      determined by the clinical response.

PMID- 9770040
TI  - [Neuropeptides: their role in nasal physiology].
AB  - In a review of the literature, the authors have studied the biochemical aspects
      of the sensory physiology of the nasal mucosa. In a previous publication, the
      abundant presence of neuropeptides in the afferent sensory nerves of the
      pituitary gland was studied. In this work, the authors have sought to determine
      the physiological role of these molecules in transmitting messages of aggression,
      and their implication in the defense mechanisms.

PMID- 9770041
TI  - [Anatomy of nasal obstruction. The recognition of the role of septum. Its
      application to the surgical treatment of nasal obstruction].
AB  - A retrospective study of the records of 392 consecutive patients prospectively
      operated for non-vasomotor nasal obstruction, has allowed us to identify a
      syndrome that we would call morphological syndrome. This is caused by anatomical
      deformities of the nasal septum, inferior turbinate hypertrophy frequently found
      being the most often only a compensation for the septal deviation. This endonasal
      abnormality, which can be congenital or post-traumatic, is most frequently of
      developmental origin and therefore most often found in Caucasian men, whose
      facial and septal growth is considerable. This morphological syndrome comprises
      unilateral or bilateral nasal obstruction, noisy nocturnal breathing (20% of
      patients), a posterior nasal drip (38% of patients), frontal headaches (49% of
      patients) and recurrent viral or bacterial rhinosinusitis (36% of patients).
      Other associated symptoms include epistaxis, olfactory dysfunction (hyposmia) and
      the manifestations of eustachian tube dysfunction. That this syndrome exists is
      confirmed by the effectiveness of septoplastic operation, performed in our
      hospital according to the method of Cottle, but without any surgical associated
      intervention on the inferior turbinates. This operation is an effective treatment
      both in a global fashion (95% of good results) and in relation to each of the
      symptoms (except postnasal drip) and is stable in the longterm and well tolerated
      (minor associated morbidity). This study allow us to re-establish the almost
      exclusive role of the nasal septum in the genesis of morphological nasal
      obstruction.

PMID- 9770042
TI  - [Labyrinthine fistulae and cholesteatoma].
AB  - The case notes of 33 patients with labyrinthine fistulae have been studied; they
      have been found in 10% of cholesteatomas. The usual site is the lateral
      semicircular canal. Only 17 patients experienced vertigo, 2 had total deafness,
      and 14 others had a mixed deafness. Scanning with fine cuts in both the axial and
      coronal planes demonstrates the lesion definitively in 70% of cases, but the
      fistula may be discovered only at operation, either in the lateral semicircular
      canal, or especially at the level of the oval window (5 cases). The authors
      usually use the closed technique (26 cases), and always seek to remove the matrix
      in its entirety, followed by the use of bone powder to close the fistula. In 2
      patients there was a loss of hearing on bone conduction at 4 and 8 KHz, and only
      one had total loss of hearing. No patients had vertigo persisting after 6 months.
      The indications and results are compared with those found in the literature. It
      now seems unusual to experience postoperative sensory-neural hearing loss
      provided that the presence of a fistula is recognised early on, and that the
      covering of squamous epithelium is removed completely atraumatically at the last
      part of the operation.

PMID- 9770043
TI  - [Results of vestibular neurotomy from a socio-professional point of view].
AB  - Vestibular neurotomy, in addition to the fact that it preserves the hearing, is
      considered to be the most effective form of treatment for incapacitating
      unilateral Menieres disease which is resistant to medical treatment. The authors
      have carried out a retrospective study of 20 cases of vestibular neurotomy
      operated on between 1986 and 1996. They have evaluated the results of the
      suppression of vertigo and the improvement of quality of life. Each patient was
      given a questionnaire. The parameters studied were the quality of daily life,
      professional life and driving ability. The mean follow-up period was 3 years.
      This study confirms the good results obtained with vestibular neurotomy for
      vertigo: complete control of attacks of vertigo was obtained in 90% of cases
      according to the criteria laid down by the American Committee on Hearing and
      Balance, as modified in 1985 (AAO, 1985). This study has also confirmed that the
      quality of patients lives is greatly enhanced both for everyday activities,
      professional activities and driving.

PMID- 9770044
TI  - [Schwannoma of the cervical esophagus: case report and clinical and pathological
      analysis].
AB  - Neurogenic tumors fo the head and neck are relatively rare and often mistaken for
      other disease processes. Schwannoma (neurinoma, neurilemoma, neurolemoma) is a
      tumour histologically characterized by the proliferation of schwann cells from
      the neural sheath of autonomic, cranial or peripheral nerves. We describe a case
      of schwannoma located in the muscular layer of the cervical esophagus. The
      clinical and radiological findings are highlighted allowing a retrospective
      preoperative presumption of schwannoma. Esophageal schwannoma is a very rare
      entity as only nine cases have been reported so far.

PMID- 9770045
TI  - [Lasers used by a young surgeon for stapes surgery].
AB  - We report the results of the first 38 stapes operations performed by a young
      surgeon. He achieved a perfect closure of the air-one gap (within 10 dB) in 89%
      of the patients operated on with the laser, compared with 65% of the patients
      operated on without laser. We discuss the significance of this difference, taking
      into account the multiple factors influencing the results. In our opinion, the
      laser helps a young surgeon to accelerate his learning curve in stapes surgery.

PMID- 9770046
TI  - [Fixation of nasogastric tubes in agitated and uncooperative patients].
AB  - To prevent extubation, nasogastric tubes (NGT) were attached to a fine bore
      polyurethane tube, which loops loosely around the nasal septum. In a prospective
      study 180 cases were evaluated concerning the efficacy and possible complications
      related to this techniques. On average, a nasal septal loop (NSL) remained 20.1
      +/- 1.3 days and a NGT 14 +/- 0.9 days. Complications were rare. In 45 of the
      cases NGT had to be replaced after self extubation and in 2.2% extubation
      presented more than twice. We think NSL is an easy and useful technique to secure
      NGT in non-cooperative and/or agitated patients for a relatively short term
      enteral nutrition or gastric decompression.

PMID- 9770047
TI  - [Selection of electrophysiological investigations for diagnosis in idiopathic
      facial palsy. Twenty years experience in an ENT department].
AB  - Electrophysiological exploration of the facial nerve requires different tests to
      differetciate the importance of the block, denervation and canal conduction. We
      must answer five questions: 1) Assessing the degree and the phase of the nerve
      lesion, 2) Deciding on the advisability of a facial decompression in the early
      stage of the palsy, 3) Evaluating the prognosis, 4) Choosing the best therapeutic
      approach, 5) Detecting facial hyperkinesis in an infraclinic period. In order to
      answer these questions, we select the following methods: 1) Quantified
      Electroneuronography should be applied as early as the 2nd day after onset,
      repeated on the 7th and 10th days. Unfortunately this is not always possible for
      practical reasons. In any case a minimum of two investigations should be
      performed during the 12 first days. 2) We add Computer EMG in order to control
      the evolution of the blocked fibers with regard to denervated fibers. 3) Blink
      reflex and Stapedius reflex are investigated from the 3rd day. After the acute
      phase of the palsy, recovery is detected by the reappearance of the blink and
      stapedius reflexes and the evolution of the computed EMG. These tests are
      sufficient for answering the five questions mentioned above without discomfort
      for the patient.

PMID- 9770048
TI  - ABR and HIV-induced impairment of the central nervous system.
AB  - This in vivo study used Auditory Brainstem Responses (ABR) to evaluate nerve
      transmission integrity in the course of HIV infection. 48 normoacoustic HIV+
      patients (40 men, 8 women) and 10 healthy age, sex and risk-factor matched
      controls underwent Brainstem Evoked Auditory potentials using a standard
      technique. Potentials were tested at cadences of 11 and 51 stimuli per second.
      ANOVA and Student's T test were used for inter Center for disease Control (CDC)
      classes and CDC classes vs control analysis of the values of the principal wave
      latencies (I, III, V) and interpeak intervals (I-III, III-V, I-V). Significant
      impairments in nerve transmission, shown best at the 51 pps cadence, were present
      from the earliest stages of HIV infection and worsened as the disease progressed.
      These results suggest that the upper part of the brainstem may be the main target
      of involvement in the tract being tested. Since electrophysiological tests allow
      detection of nervous dysfunction in subjects while still asymptomatic, these
      procedures could be usefully employed in order to better define the real onset of
      brain damage in HIV-1 seropositive patients and monitor the speed with which
      these lesions evolve.

PMID- 9770049
TI  - Value of computed tomography of the temporal bone in acute otomastoiditis.
AB  - In this study we report our experience with 24 patients with acute mastoiditis
      treated at the University Hospital in Ghent, Belgium. The most common presenting
      signs and symptoms of acute mastoiditis were an abnormal tympanic membrane
      (21/24), otorrhea (17/24) and earache (13/24). Postauricular edema and erythema
      with protrusion of the ear, often used as a diagnostic criterion, was present in
      only 3 patients. Demineralisation of the trabeculae was the most frequent
      radiological finding (13/24). Based on CT findings a distinction was made between
      two groups: acute incipient mastoiditis (13/24) and acute coalescent mastoiditis
      (5/24). Thirteen patients recovered with conservative therapy consisting of IV
      antibiotics and early myringotomy with or without placement of a ventilation
      tube. Mastoidectomy was required in 11 patients. Nine patients presented with a
      complication of infection extending beyond the mastoid compartment. The results
      are discussed and the value of CT scanning as a diagnostic tool and decisive
      element in the choice of therapy is analysed.

PMID- 9770051
TI  - Cancer of the larynx: correlation of clinical characteristics, site of origin,
      stage, histology and diagnostic delay.
AB  - The authors studied the records of 108 cases of cancer of the larynx registered
      at the Department of Otolaryngology--Clinics Hospital--Faculty of Medicine of
      University of Sao Paulo, from 1985 to 1995. Dysphonia was the most common symptom
      observed (85.2%), independently of the site of the tumor. Dysphagia, dyspnea and
      weight loss had a similar incidence (32.4%; 34.3%; and 29.6%, respectively), with
      dysphagia more frequent in tumors which affected the supraglottis and dyspnea in
      glottic and subglottic tumors. As to staging, 45.8% presented at stage IV at the
      first consultation, and only 13.5% at stage I. No association was observed
      between tumor size (according to the TNM classification), presence of lymph node
      involvement, and delay, in diagnosis, taking the period between the beginning of
      symptoms and the first consultation at the hospital. In relation to the
      presenting symptom those with dysphonia sought medical help later. There was no
      correlation between histological invasion and tumor stage. It was concluded that
      the stage at presentation of tumors of the larynx is possibly more related to
      intrinsic differences in the tumor's aggressiveness and in host characteristics
      than to the diagnostic delay, and that it is necessary to warn the population
      about symptoms which may suggest the presence of cancer of the larynx.

PMID- 9770050
TI  - [A prospective study of ENT complication following surgery of the cervical spine
      by the anterior approach (preliminary results)].
AB  - In order to evaluate complications due to cervical spine surgery using the
      anterior cervical approach a prospective study was conducted on 125 patients. ENT
      examination with the fibroscope was employed for all the patients before the
      procedure. The patients were operated on under general anesthesia and were
      intubated with an armoured tube, and then were placed in an intensive care unit
      for 24 hours. Assessment of deglutition and an ENT examination were performed the
      day after surgery. Before surgery, two cases of vocal cord paralysis were noted.
      111 patients (88.8%) presented with subjective disorders: problems such as sore
      throat, odynophagia, dysphagia, dysphagia with overspill and hoarseness were
      respectively noted in 55 (44%), 34 (27.2%), 32 (25.6%), 11 (8.8%) and 13 (10.4%)
      cases. Dyspnoea was found in 2 cases (1.6%). 117 patients (93.6%) presented
      postoperative anomalies which were found on the posterolateral pharyngeal wall,
      on the arytenoids and on posterior third of the vocal cords. Inflammatory and/or
      swollen lesions were slight, moderate, significant or very significant in
      respectively 22.4%, 22.4%, 15.2% and 1.6% of cases. Very significant
      circumferential swelling of the pharyngeal wall and of the arytenoids was
      responsible for two cases of respiratory distress, and the patients required
      reintubation and return to theatre. Severe pharyngeal lesion correlated with
      duration of surgery (r = 0.20; p < 0.05), with the number levels of fusion (r =
      0.02; p < 0.02) and with the age of the patient (p < 0.02). Six patients
      presented problems of mobility of the vocal cords: 3 had a right vocal cord
      paresis which was temporary and 3 had paralysis, also on the right but which
      persisted. There were no other complications. It is concluded that (i) ENT
      complications are frequently found in postoperative cervical spine surgery using
      the anterior cervical approach, some of them being severe. An ENT examination
      must be performed before the procedure for legal reasons. It is also recommended
      in the postoperative period in the case of discomfort; (ii) patients need to be
      placed in an intensive care unit during for the first 24 hours (iii). This study
      needs to be attended over more patients (iv) comparison with a control group of
      patients having non cervical surgery and intubated in the same way is needed to
      differentiate lesions related to surgery or intubation.

PMID- 9770052
TI  - [Adenoid cystic carcinoma of the larynx. A case report and review of the
      literature].
AB  - Laryngeal adenoid cystic carcinoma (ACC) is a rare disease due to the poor
      distribution of the accessory salivary glands in this area. The authors describe
      a case of ACC arising from the sus glottic area and underline the difficulty of
      such a diagnosis, which is in fact an histologic finding. The signs of discovery
      of a laryngeal ACC are not different from other tumors of the area, except pain
      frequently evoked in these tumors. Laryngeal ACC arises exceptionally before the
      age of 20 years and no risk factor is known. The most frequent localization is in
      the sub-glottic area, but sus glottic and glottic localizations have been
      reported. Evolution is marked by the onset of cervical lymph adenopathies and
      systemic metastasis most often located in the lung. The treatment comprises wide
      surgical exerisis followed by radiotherapy. Other reports seem to indicate that
      the pronostic of the laryngeal location of this disease is worse than in other
      areas of the head and neck.

PMID- 9770053
TI  - [Melkersson-Rosenthal syndrome: clinical features and a suggested diagnostic
      grading system].
AB  - The case history of a patient with orofacial oedema is presented, together with
      the findings on extensive investigation. A diagnosis of Melkersson-Rosenthal
      syndrome (MRS) was made. This case demonstrated the difficulties in diagnosis in
      monosymptomatic cases, and the importance of further investigation (EMG). MRS is
      a rare condition with a triad of symptoms: orofacial oedema, facial palsy, and
      plicated or "scrotal" tongue. The pathogenesis is unknown. The vital prognosis is
      good. Treatment has not been specific. It relies on local (intra-lesional) and
      systemic steroids, and elective eyelid surgery. Clofamizine has proved an
      effective alternative treatment.

PMID- 9770054
TI  - [A difficult diagnosis of a congenital minor ear anomalie].
AB  - We report an unusual congenital middle ear anomalie with an inflammatory tympanic
      membrane, a total opacity of the middle ear on the CT scan and a tumor in the
      mesotympanum.

PMID- 9770055
TI  - [Treatments of idiopathic sudden sensorineural hearing loss: retrospective study
      of 144 cases].
AB  - In this report of a retrospective study of 144 cases of idiopathic sudden hearing
      loss, two important prognostic indicators appear: the elapsed time since the
      onset of symptoms and the degree of hearing loss. According to these indicators,
      the authors define three group of patients with a recovery rate of 65%: patients
      with a threshold hearing level of less than 40 dB, treated within two months of
      the onset of their hearing loss, patients with a threshold hearing level between
      40 and 70 dB treated within one month and patients with a threshold hearing level
      of more than 70 dB treated within 7 days. Patients with a threshold hearing level
      of more than 70 dB, treated between 7 and 30 days, have only a partial recovery
      in 40%. The evaluation of efficacy of various treatment demonstrates a slight
      improvement of the hearing loss using steroids associated to vasodilatators, even
      if no significant difference is found between the different therapies. The
      normovolemic hemodilution and the treatment included mannitol seem to be
      ineffectual.

PMID- 9770056
TI  - [Comparison of different treatments of acute acoustic trauma].
AB  - Comparison between different treatments of acute acoustic trauma. The acute
      acoustic trauma, induced tinnitus, hearing loss and an fickle otalgia, is a
      Permanent or a Temporary Threshold Shift. In a retrospect study of 184 patients,
      or 313 cases, the target of this research was to determinate a possible level of
      blood dilution resulted during normovolemic hemodilution, and an optimal
      therapeutic group. In fact, just the dilay of a starting treatment between 0 and
      3 days permitted to obtain this group on qualitatives and quantitative criteria;
      efficiency of the treatment is better than the damages are important. We observed
      an important post normovolemic hemodilution effect on audition recovery and
      tinnitus evolution. In return, an optimal hematocrite value hadn't been found
      between 29 and 35%.

PMID- 9770057
TI  - [Acoustic neurinoma and facial nerve].

PMID- 9770058
TI  - [Functional surgery on the acoustic-facial pedicle].
AB  - The authors present their expertise and their results concerning the functional
      surgery on the acoustic facial nerve bundle in various disorders such as
      incapacitating vertigo, hemifacial spasm and tinnitus.

PMID- 9770059
TI  - [The facial nerve and the retrosigmoid approach].
AB  - The author gives an account of his experience with the retrosigmoid approach, and
      emphasizes the preservation of the facial nerve and hearing. A detailed
      description of the operative technique is given. This approach is used when it is
      intended to conserve the hearing. The series consists of 2 stage III cases and 26
      stage I and II cases. The two stage III cases had total deafness. For the other
      stages, 25 patients had normal facial function postoperatively. The hearing was
      preserved in 9 cases in the frequency range 500-1000-2000 Hz, with thresholds of
      less than 30 dB, and in 7 of cases these criteria were also true for the 4000 Hz
      frequency. The author feels that the retrosigmoid approach with facial nerve
      monitoring provides the same degree of safety for the facial nerve as the
      translabyrinthine approach for surgery of stage I and II tumours.

PMID- 9770060
TI  - [Enlarged middle fossa approach to the cerebello-pontine angle. Technique and
      indications].
AB  - Our enlarged middle fossa approach, first published in 1982, aims to expose the
      internal auditory meatus and cerebello-pontine angle from above, with
      preservation of the cochlea and labyrinth. The steps of the operation are
      described, especially certain technical details: the skin incision, resection of
      the squamous temporal bone, extradural exposure of the petrous temporal bone,
      subsequent resection of the middle meningeal artery and superior petrosal sinus,
      extensive bone removal behind and in front of the internal auditory meatus,
      opening of the dura mater to expose the brain stem, and plastic closure of the
      defects. Believing in the advantages of this approach, we have modified the
      technique for various indications, including decompression of the facial and
      cochleovestibular nerves for cases of vascular compression and Meniere's disease;
      management of temporal bone fractures with CSF leak of facial nerve damage;
      extensive cholesteatoma of the petrous bone; meningiomas or other tumours of the
      petrous bone; neuromas of the facial or vestibular nerve. It should be emphasised
      that the middle fossa approach may be combined with other approaches in the
      resection of lateral skull base tumours with preservation of the inner and middle
      ear.

PMID- 9770061
TI  - [Significance of lasers in surgery of cerebellopontine angle tumors].
AB  - The use of the laser in otology has demonstrated its effectiveness and safety.
      The aim of this paper is to show its application in otoneurosurgery. After
      comparing the advantages and disadvantages of various lasers (Yag, CO2, KTP), we
      soon opted for the KTP laser, which we have since used exclusively in otology and
      otoneurosurgery. 25 patients with cerebello-pontine angletumours were operated
      using the KTP laser (22 neuromas and 3 meningiomas). Although in the absence of
      rigourous methodology it is difficult to assert the superiority of the laser over
      the classical techniques of resection, the results seem better since we have been
      using the laser for otoneurosurgery, especially for facial function. In any case,
      the laser is merely an instrument, which it is necessary to learn to manipulate;
      it does allow lesions to be vaporized without traction, and has a haemostatic
      action. It should never be used directly in contact with nervous structures,
      especially nerves. It seems to us to be most helpful in dealing with large and
      very vascular tumours.

PMID- 9770062
TI  - [Taste and lacrimation after acoustic neuroma surgery].
AB  - AIM OF THE STUDY: Postoperative sensory component of the facial nerve after
      acoustic tumor surgery has received little attention in the literature. The
      object of the present investigation was to review this specific topic analyzing
      the postoperative frequency of taste and lacrimation (crocodile tears or dry eye)
      abnormalities. MATERIAL AND METHODS: 54 patients who underwent acoustic tumor
      removal were selected for this study. Each of these patients was recalled and pre
      and postoperative evolution of the sensory dysfunction were assessed. The latters
      were correlated with the facial function evaluated according to the House
      Brackmann classification. RESULTS: Postoperative taste dysfunction (reduced or
      changed sensation) was complained by 38.5% of the patients. After surgery, 42.3%
      of the cases had crocodile tears, while in 59.6% altered tearing occurred.
      DISCUSSION: The present study, according to the Irving et al's experience
      confirmed a significant incidence of postoperative abnormal function of the
      sensory facial nerve. The influence of the motor component on these outcomes was
      variable. Lacrimation worsened when facial function was poor. On the other hand,
      grades V or VI did rarely manifest crocodile tears. Clinically, these findings
      implies the importance of a preoperative counseling of such particular aspect in
      the candidates to surgery of acoustic neuroma in order to adequately motivate
      them and, at the same time, to reduce their psychological discomfort.

PMID- 9770063
TI  - [Oto-neuro-surgical approach and accessibility to the cochlear nuclei.
      Significance in auditory brain stem implant].
AB  - The auditory brainstem implant (ABI) is now used to stimulate the cochlear
      nucleus to obtain auditory perception in patients with type 2 neurofibromatosis.
      Only electrical stimulation of the cochlear nucleus complex, in the lateral
      recess of the fourth ventricle, can achieve auditory rehabilitation of these
      profound bilateral retrocochlear deafness. With 20 standard translabyrinthine
      approaches, our personal anatomical study propose to describe surgical landmarks
      of the cochlear nuclear complex and surgical accessibility of the lateral recess
      of the fourth ventricle. The root of vestibulocochlear nerve, the
      glossopharyngeal nerve and the choroid plexus of the fourth ventricle might have
      surgical significance because of their reliability.

PMID- 9770064
TI  - [Parotid tumors: a report of 120 cases].
AB  - The treatment of the parotid tumors was clarified for a majority of the tumors,
      in spite of her histology diversity. The authors report in a retrospective study
      120 cases of a parotid gland tumors during ten years over. They insist on the
      difficult of therapeutics, the histological diversity and the complications and
      sequelles of the surgery. The diagnosis was especially clinical and completed by
      scan and or a sialography. The superficial or total parotidectomy with
      preservation of facial nerve was realized in eighty-nine percent. The functional
      courage and the radiotherapy were associated respectively in eleven and seventeen
      patients. The histology was dominated by the benign tumors. The complications and
      sequelles were a facial paralysis definitive and a Frey's syndrome respectively
      in three percent cases. The ninety-seven percent patients were controlled with a
      mean follow up of three years. After results we must know every histologic type
      for to adapt his treatment. And the same complications and the sequelles were
      noted in all surgery type.

PMID- 9770065
TI  - [Pyolaryngocele: a rare cause of respiratory distress].
AB  - Pyolaryngocele is an unusual diagnosis, occurring as a complication of a
      laryngocele, witch may be discovered because of an episode of acute respiratory
      distress needing urgent medical care. This is a case report with confirmation of
      the diagnosis by CT scan, which needed surgical treatment.

PMID- 9770066
TI  - [Fistula of the 4th endobranchial pouch: a case report].
AB  - The congenital fistula of the 4th branchial pouch is rare. Clinical and
      therapeutic difficulties are often found. The authors describe a new case of
      fistula of the fourth endobronchial pouch and precise the embryogenesis, the
      clinical diagnosis and the surgical treatment.

PMID- 9770067
TI  - [Fistula of the 4th endobranchial pouch: a case report].
AB  - Fourth branchial arch fistula are rare. Their diagnosis is difficult and anknow.
      It is confirmed by fistulography and endoscopy. It's an surgical treatment.

PMID- 9770068
TI  - [A voluminous exteriorized odontogenic keratocyst].
AB  - The authors report the case of a 63 years old man who presented a voluminous
      exteriorized keratocyst of the jaw. We have first made a punction of the cyst in
      order to facilitate the operation. Anatomopathological examination of the liquid
      found epithelial cells. We collected the keratocyst by a non interrupting
      mandibulotomy via cervical incision.

PMID- 9770069
TI  - Unusual extracranial complications of otitis media in a young HIV patient:
      retropharyngeal and Mouret's abscess.
AB  - Since the introduction of antibiotic therapy, the incidence of intra- and
      extracranial suppurative complication of acute and chronic purulent otitis media
      has sharply decreased. In particular, reports of laterocervical abscesses
      secondary to this disorder are quite rare, not more than twenty cases of Bezold's
      or Mouret's abscesses having been reported in the literature during the last ten
      years. The authors present a case of retropharyngeal and Mouret's abscess
      developed as a consequence of acute purulent otitis media in a young Aids
      patient. True otologic manifestations of Aids are rare while the incidental
      association of otologic disease with Aids is more common. The development of
      complication in the present case is favoured by the patients severe
      immunodepression.

PMID- 9770070
TI  - [Pharyngeal tuberculosis: an analytical study and report of 10 cases].
AB  - Pharyngeal tuberculosis is an uncommon condition. We report here an analysis of
      10 cases collected from 1990 to 1996. The patients were aged between 16 and 75
      years, with an equal sex distribution. Topographically there were 7
      nasopharyngeal cases and 3 tonsillar cases, the presenting features being those
      of a chronic pharyngeal disorder, sometimes with cervical adenopathy.
      Macroscopically, the main features were those of misleading pseudo-tumours. The
      diagnosis rests on the histology. Anti-tuberculous medical treatment is usually
      effective.

PMID- 9770071
TI  - Analysis of defective genomes of bombyx mori nucleopolyhedrovirus generated by
      serial undiluted passage in cell culture.
AB  - Viral DNA was extracted from cells infected with bombyx mori nucleopolyhedrovirus
      (BmNPV) D1 strain after 34 serial undiluted passages (P34). P34 DNA was subjected
      to restriction analysis and Southern blot hybridisation using standard D1 DNA and
      P34 DNA of BmNPV as probes. Based on hybridisation profiles, the BmNPV DNA
      regions retained in the P34 DNA were localised on HindIII and PstI restriction
      maps. Two regions of BmNPV DNA located at 0-12.8 and 40.2-65.0 map unit (m.u.)
      were highly conserved in P34 DNA. These regions contained two of three
      interspersed homologous sequences (ihss), but only one of five homologous regions
      (hrs). This suggests that ihss may have an essential role in BmNPV replication.

PMID- 9770072
TI  - Strain variability of plum pox virus isolates from western Slovakia.
AB  - Leaf tissues of stone fruit trees (plum, apricot, peach and myrobalan) carrying
      symptoms of plum pox virus (PPV) infection and of peach GF 305 seedlings and
      Nicotiana benthamiana infected experimentally with PPV were assayed for PPV by
      polymerase chain reaction (PCR). The expected 243 bp PCR products were subjected
      to restriction fragment length polymorphism (RFLP) analysis with restriction
      endonucleases AluI and RsaI. All of the PCR products contained the AluI site. The
      RsaI restriction profiles of the PCR products demonstrated the prevalence of PPV
      M subgroup in the tested samples from western Slovakia.

PMID- 9770073
TI  - Antiviral effect of proline-rich polypeptide in murine resident peritoneal cells.
AB  - It is known that resident peritoneal (RP) cells from BALB/c female mice express a
      constitutive non-specific antiviral immunity which is progressively reduced
      during several days of cultivation in vitro. In this report, we have studied the
      effect of a proline-rich polypeptide (PRP) isolated from ovine colostrum on the
      kinetics of vesicular stomatitis virus (VSV) replication in freshly isolated and
      one-day cultured RP cells. The polypeptide was added to the cells immediately
      after virus adsorption or one day before or after viral infection. Independently
      on time of PRP addition, an inhibition of VSV replication (virus titres reduced
      by up to 4 log units) was observed. Occasionally, however, a weak stimulation of
      VSV replication by PRP (virus titres increased by 1-2 log units) was noticed in
      RP cells constitutively resistant to the infection.

PMID- 9770074
TI  - Detection of abnormal lymphocytes in the blood of Balb/c mice infected with
      murine gammaherpesvirus strain 72: the analogy with Epstein-Barr virus infection.
AB  - We have followed the effect of murine gammaherpesvirus strain 72 (MHV-72)
      infection and immunosuppression on the differential white blood cell count of
      Balb/c mice. In both the acute and chronic phase of infection, abnormal
      lymphocytes resembling human B lymphocytes infected with Epstein-Barr virus (EBV)
      were detected. Immunosuppression had no significant effect on the haematological
      changes during the infection. Some of mice, which had developed tumours as a
      consequence of infection, showed splenomegaly, lymphadenopathy, leukocytosis and
      high percentage of immature blastic forms of leukocytes.

PMID- 9770075
TI  - Potato virus A detection by reverse transcription-polymerase chain reaction.
AB  - Simple and reliable procedure for sample preparation and reverse transcription
      polymerase chain reaction (RT-PCR) detection of potato virus A (PVA) is
      described. PVA-specific primers used in the RT-PCR defined a target sequence of
      321 bp and did not produce amplification product(s) with potato virus Y.

PMID- 9770076
TI  - Quarantine strawberry vein banding virus firstly detected in Slovakia and Serbia.
AB  - Strawberry vein banding virus (SVBV) was detected by polymerase chain reaction
      (PCR) and dot-blot hybridisation in samples of cultivated strawberry plants
      originating from central Slovakia and in samples of wild strawberry plants from
      south-eastern Serbia in Federal Republic of Yugoslavia (FRY). This is the first
      finding of SVBV in these countries as well as of SVBV in wild strawberry plants
      in Europe.

PMID- 9770077
TI  - Sequence analysis of a fragment of rOmpA gene of several isolates of spotted
      fever group rickettsiae from China.
AB  - The nucleotide sequence of rOmpA gene fragment of three Chinese isolates of
      spotted fever group rickettsiae (SFGR) (BJ-90, Ha-91 and HLJ-054) was determined.
      The obtained nucleotide and putative amino acid sequences were compared with
      those of another Chinese SFGR isolate (HL-93) and several prototype SFGR strains.
      This comparison showed that the isolates BJ-90 and Ha-91 are closely related to
      each other and R. sibirica but different from the isolates HLJ-054 and HL-93. We
      assume that with exception of the isolates HLJ-054 and HL-93 that represent new,
      unique members of SFGR, the isolates BJ-90 and Ha-91 are closely related to R.
      sibirica, one of the prototype SFGR strains.

PMID- 9770078
TI  - Isolation and characterization of the dnaA gene of Rickettsia prowazekii.
AB  - The dnaA gene encoding the initiator protein of DNA replication was isolated from
      the obligate intracellular bacterium, Rickettsia prowazekii. Comparison of the
      deduced amino acid sequence of R. prowazekii DnaA with other bacterial DnaA
      proteins revealed extensive similarity. However, the rickettsial sequence is
      unique in the number of basic lysine residues found within a highly conserved
      portion of the putative DNA binding region, suggesting that the rickettsial
      protein may recognize a DNA sequence that differs from the consensus DnaA box
      sequence identified in other bacteria. Consensus DnaA box sequences, found
      upstream of many bacterial dnaA genes, were not identified upstream of
      rickettsial dnaA gene. In addition, gene organization within this region differed
      from that of other bacteria. The putative start of transcription of the
      rickettsial dnaA gene was localized to a site 522 nucleotides (nt) upstream of
      the DnaA start codon.

PMID- 9770080
TI  - First isolation of mosquito-borne West Nile virus in the Czech Republic.

PMID- 9770079
TI  - The role of herpes simplex virus glycoproteins in the virus replication cycle.
AB  - At least nine of the eleven herpes simplex virus (HSV) glycoproteins so far known
      have been widely characterised as regards their role in the virus replication
      cycle. During early virus-to-cell adsorption ("adsorption"), glycoprotein C (gC)
      interacts with the glycosoaminoglycan (GAG) heparan sulphate (HS), located on the
      cell membrane surface. This interaction is labile until other glycoproteins such
      as B and D (gB and gD) begin to participate in the entry process. gB also
      harbours a site for interaction with GAGs, while gD provides a stabile attachment
      to cellular receptors ("receptors") such as the herpesvirus entry mediator
      (HVEM). Late adsorption is associated with a conformation change of gD occurring
      after the receptor binding, a step followed by interaction of gD with the gH/gL
      heterodimer (complex). Fusion domains of the gH/gL complex and gB enable the pH
      independent virus-into-cell penetration ("penetration"). The gE/gI complex and gM
      interact with the receptors at cell junctions in order to facilitate cell-to-cell
      spread of the virus along the basolateral surface of polarised cells and/or a
      similar intercellular spread in nonpolarised cells by avoiding virion release,
      gK, the only so far known HSV-coded glycoprotein which is not incorporated into
      virions, plays an essential role in the virus capsid envelopment at the nuclear
      membrane and in the virion transport to the cell surface. Unusually large
      polykaryocytes arise due to mutations in syn (syncytium) loci of the viral
      genome, which were mapped to UL53 (syn1) and UL27 (syn3) genes coding for gK and
      gB, respectively, while the genes UL20 and UL24 (both syn5) code for
      nonglycosylated cell membrane-associated proteins ("membrane proteins"). The
      products of nonmutated syn genes either downregulate the fusion of plasma
      membranes of infected cells ("membrane fusion") or protect them from undesirable
      fusion events.

PMID- 9770081
TI  - 32 bp deletion in CCR-5 gene and human immunodeficiency virus epidemic in the
      Czech Republic.

PMID- 9770082
TI  - Prevalence of human herpesvirus 8 antibodies in human immunodeficiency virus type
      1-infected homosexual men in Slovakia.

PMID- 9770083
TI  - Proceedings of the 1st Asian Research Symposium in Rhinology (ARSR). Suzuka, Mie,
      Japan. November 28-30, 1996. Abstracts.

PMID- 9770085
TI  - [Neuromuscular monitoring. Standard procedures].
AB  - In this article current indications and limitations of neuromuscular monitoring
      are reviewed. Attention is mainly focused on detection of residual curarisation.
      New insights in the pathophysiological consequences of residual neuromuscular
      blockade and the actual criteria of complete recovery are discussed. Surprisingly
      in this context, despite the benefit of neuromuscular monitoring, its utilisation
      in clinical practice is rather an exception than the routine. A lack of
      standardisation of neuromuscular monitoring is probably the major problem on the
      way to a widespread utilisation of the monitoring.

PMID- 9770086
TI  - [Ondansetron. Prophylaxis and therapy of nausea and vomiting following major
      gynecologic procedures. Results of a national multicenter study].
AB  - This investigation was conducted as a national multicenter study to evaluate
      effectiveness and safety of prophylactic and therapeutic ondansetron for
      postoperative nausea and vomiting (PONV) in major gynaecological surgery.
      METHODS: 387 patients were randomised to receive either ondansetron 8 mg or
      placebo i.v. prior to anaesthesia induction. Anaesthesia was performed with a
      volatile anaesthetic, nitrous oxide and opioids. Established PONV was treated
      with ondansetron 4 mg i.v. Postoperative evaluation included time, duration and
      severeness of nausea and vomiting in the first 24 h after the operation. RESULTS:
      In the study period the incidence of emesis was 35% after prophylactic
      ondansetron and 58% after placebo (p < 0.01). Nausea occurred in 49% and 64%
      respectively (p < 0.01). 28% after prophylactic ondansetron and 48% after placebo
      required ondansetron therapy (p < 0.01). The number of adverse events was small
      in total and comparable for both groups. CONCLUSION: Our investigation proves the
      efficiency of ondansetron 8 mg prior to induction of anaesthesia in preventing
      PONV. Furthermore, our results demonstrate the safety of the drug for prophylaxis
      and therapy.

PMID- 9770087
TI  - [Risk factors and frequency of adverse effects after autologous blood donation].
AB  - OBJECTIVE: Autologous blood donation before elective surgery decreases the
      perioperative risk although donation itself can cause adverse effects. Are there
      specific donor characteristics, which influence the frequency and severity of
      adverse effects? METHODS: We investigated in a prospective study 3603 autologous
      blood donations including registration of patient's age, gender, height, weight,
      medical record and risk-score by Bocker. The adverse effects were divided into
      severity groups (SG). The investigation took place in a Department of
      Anaesthesiology and Intensive Care Medicine in an university hospital. 1041
      patients with preoperative autologous blood donation were investigated between
      January 1995 and April 1997. RESULTS: 7.4% of patients had adverse effects.
      Hypotension and bradycardia were the most frequent adverse effects. 4.3% of the
      adverse effects were graded as minimal (SG 1), 2.4% as mild (SG 2) and 0.7% as
      moderate (SG 3). The rate was higher in young donors (< 25 years). For all other
      donor characteristics including older age, cardiac or pulmonary diseases and high
      risk-score no higher donation risk was observed. CONCLUSIONS: Adverse effects
      during and after autologous blood donation are rare. Predictor for reaction seems
      to be young age (< 25 years). Referring to donor's characteristics and
      predonation risk factors it is hardly possible to predict adverse effects. Thus,
      all autologous blood donors require adequate monitoring by a physician. Under
      these circumstances the autologous blood donation is a safe procedure even in
      patients with severe risk factors.

PMID- 9770088
TI  - [The effect of gamma-hydroxybutyrate (GHB) on proinflammatory cytokine gene
      expression in coronary surgical procedures].
AB  - OBJECTIVE: To determine the influence of gamma-hydroxy-butyrate (GHB) on
      spontaneous and lipopolysaccharide (LPS)-stimulated release of tumour necrosis
      factor-alpha (TNF), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and
      interleukin-10 (IL-10) in whole blood from patients undergoing coronary artery
      bypass grafting (CABG) with extracorporeal circulation (ECC). In addition, the
      pharmacological modulation on lipopolysaccharide (LPS)-stimulated cytokine
      release by GHB (GHB-Na and GHB-ethanolamide) was characterized in a separate in
      vitro-assay. METHODS: In a prospective, randomized, double-blinded study, 12
      patients undergoing elective CABG were assigned to receive either saline
      (control) or GHB-Na (25 mg/kg as loading dose followed by 25 mg/kg/h)
      intraoperatively. Blood samples were obtained (A) preoperatively, (B) 20 min
      after ECC and (C) 24 h after ECC. Plasma levels (spontaneous release) as well as
      LPS-stimulated cytokine secretion were measured in a whole blood culture system
      ex vivo and correlated with mRNA-expression in peripheral blood mononuclear cells
      (PBMC). In addition, the dose-response characteristics of modulation of the
      cytokine response by GHB was studied in vitro in the same assay. RESULTS: Plasma
      IL-6 and IL-10 levels were significantly elevated after CABG, while TNF and IL-1
      beta were detectable only occasionally in both groups. Expression of all
      cytokines studied was significantly reduced upon ex vivo LPS-stimulation at time
      point B. Despite maintained expression of TNF and IL-1 beta mRNA-transcripts upon
      ex vivo LPS-stimulation in patients treated with GHB, release of the cytokines in
      the supernatant was decreased to a similar degree as in the control group.
      Cytokine response upon LPS-stimulation was restored 24 h after CABG for the group
      mean, however, with substantial individual heterogeneity. In vitro,
      pharmacological doses of GHB-Na (2 mg/ml) attenuated LPS-induced IL-1 beta
      release. However, application of the GHB-receptor antagonist NCS-382 caused a
      nearly complete cessation of IL-1 beta release in vitro (to 2.5% of control). GHB
      ethanolamide (LK 544) did not influence the LPS-stimulated release of the
      cytokines studied. CONCLUSION: The results suggest a biphasic response of
      stimulated PBMC cytokine gene expression during CABG with an initial tolerance to
      LPS-stimulation shortly after termination of ECC. However, whether or not PBMC
      express functional GHB receptors remains unclear in light of contradictory
      effects of the different ligands. In spite of the ex vivo and in vitro results,
      application of GHB-Na in doses which are primarily based on its use as an
      anesthetic agent do not seem to modulate the release of the cytokines studied.

PMID- 9770089
TI  - [Predictability and precision of "target-controlled infusion" (TCI) of propofol
      with the "Disoprifusor TCI" system].
AB  - In Germany a TCI-system for propofol (Disoprifusor-TCI) has been commercially
      available since spring 1997. We investigated the prediction error and precision
      of this TCI system as part of a multicentre study. Bias, precision, blood
      concentrations and dosage of propofol were compared with patients receiving
      propofol via a manually controlled infusion device. METHODS: After approval by
      the local Ethics Committee and written informed consent, 21 patients of ASA
      classification I to III scheduled for major abdominal surgery received either a
      target controlled infusion (group T, Disoprifusor-TCI) or a manually controlled
      infusion (group M) of propofol. The propofol plasma concentrations were measured
      by HPLC. The prediction error for each measurement, the median prediction error
      (MDPE) or bias, the median absolute prediction error (MDAPE) or precision and the
      divergence (change of the prediction error over infusion time) were calculated
      for both groups. RESULTS: For all patients in group T (n = 12) the bias of the
      TCI system was 6.7% and the precision 27.5%. For 70% of all measured plasma
      concentrations the absolute prediction error was < or = 37%. The divergence was 
      5.4% per hour. For all patients in group M (n = 9) the bias was 44.2% and the
      precision 50%. The mean amount of propofol infused per kilogram body weight and
      hour was significant higher in T (9.0 +/- 1.2 mg/kg/h) than in M (6.6 +/- 1.2
      mg/kg/h, p < 0.005). CONCLUSIONS: With a precision of 27.5% the investigated TCI
      system (Diprifusor-TCI) showed an acceptable inaccuracy, as for TCI-systems a
      median prediction error of +/- 30% has to be expected due to the inherent
      variability of pharmacokinetic parameters. Further studies will be necessary to
      find out whether the investigated TCI system for propofol may offer substantial
      advantages.

PMID- 9770090
TI  - [Cisatracurium in patients with compromised kidney function. Pharmacodynamic and
      intubation conditions under isoflurane-nitrous oxide anesthesia].
AB  - OBJECTIVES: The choice of cisatracurium, especially for patients with organ
      dysfunction, seems to be beneficial, because of organ-independent Hofmann
      elimination and less histamine release propensity. This study was designed to
      investigate pharmacodynamics and intubating conditions after bolus administration
      of 0.15 mg/kg cisatracurium (3 x ED95) in patients with renal failure and
      maintained with isoflurane/N2O in oxygen. METHODS: 20 patients with renal failure
      and 19 patients with normal renal function were studied. Anaesthesia was induced
      with fentanyl (2-3 micrograms/kg) and thiophentone (4-7 mg/kg). After rapid bolus
      administration of 0.15 mg/kg cisatracurium (3 x ED95), onset time and intubating
      conditions were assessed. Clinical duration (DUR 25%), recovery index and
      duration 90% were investigated by acceleromyography. Changes of mean arterial
      blood pressure and/or heart rate > or = 20% were defined as clinically
      significant. RESULTS: The onset time (3.1 +/- 0.8 min) was shorter in patients
      without renal failure (Cis-1) than in patients with normal renal function (3.6 +/
      0.8 min), but without statistical significance. Intubating conditions, scored
      according to a 3-step scale, were slightly better in patients with normal renal
      function. Other pharmacodynamic parameters did not differ significantly. However,
      a small tendency to a prolonged recovery with a wide inter-individual variety was
      characteristic for patients with renal failure. Regarding the hemodynamic
      actions, only minor individual cardiovascular changes occured. No clinical
      evidence of histamine release was observed in any patient. CONCLUSIONS: The
      result of this clinical study suggest, that cisatracurium is a suitable choice
      for patients with renal failure. The necessity for an intraoperative
      neuromuscular monitoring is given by the marked heterogeneity in the recovery
      parameters in patients with renal failure.

PMID- 9770091
TI  - [Prognosis of the apallic syndrome. A literature review].
AB  - This study evaluates the available literature about the prognosis of patients
      with apallic syndrome and similar illnesses. Different therapeutic strategies are
      not relevant in this review. The variation of the reported material did not
      permit a statistical metaanalysis. However, many interesting points of view could
      be elaborated leading to positive assistance in everyday situations. The chance
      of survival and the long-term outcome of comatose patients decrease with an
      increase in the age of the patient, the length and the degree of the coma.
      Cerebral predamage worses the long-term prognosis. Traumatic head injuries have a
      better prognosis than nontraumatic. Children (under 18 years of age) have a
      better prognosis than adults. The course of the oculomotoric symptoms can be used
      as a prognostic criterion. The somatosensory evoked potentials in the early phase
      correlate with the survival-chance and the long-term prognosis. The initial speed
      of recovery correlates with the long term outcome. Children and adults with
      traumatic apallic syndrome may recover over a period of 12 months. For apallic
      patients with other etiologies this time limit is 3 months. Few cases of recovery
      have been described outside these time limits. The average survival limit of
      permanent apallic patients is between 3 and 5 years. Particular patients have
      survived decades.

PMID- 9770092
TI  - [Postanoxia coma and prognosis. Position paper version 1.0 of the Working Group
      for Neurologic Intensive Care].

PMID- 9770094
TI  - [Tongue piercing. A fad phenomenon with anesthesiologic consequences].

PMID- 9770093
TI  - [Cesarean section with continuous spinal anesthesia in a cardiopulmonary high
      risk patient].
AB  - As a consequence of the progress in (perinatal) medicine the number of pregnant
      women with severe cardiopulmonal risk, who need caesarean delivery, is rising.
      The anaesthetic care of these patients requires optimal preparation and--as a
      prerequisite--constant intraoperative vital functions (heart rate, blood
      pressure, oxygen saturation). Typical risks like airway-problems, hypoxia, hyper-
      and hypotension and tachycardia must be strictly avoided. We report a case of
      successful caesarean delivery in a patient with severe coronary heart disease,
      using spinal catheter technique. CASE REPORT: The patient was a 36-year-old woman
      with a symptomatic coronary heart disease. Risk factors were
      hypercholesterinaemia, obesity (105 kg/168 cm), COPD consecutive to excessive
      nicotine abuse and hypertonia. Emergency admissions in the 12th and 14th
      gestation week led to the necessity of PTCA in the 15th and 19th gestation week
      in spite of pregnancy: coronary stenoses of 90% and 70% were dilated. Caesarean
      section was scheduled for 38 weeks' gestation, however due to the high risk
      involved we decided to use a continuous spinal technique. There were no problems
      with introducing the catheter (28 gauge, L3-4 interspace). Under careful
      titration a total of 2.2 ml plain bupivacaine 0.5% (spinal catheter) and 0.5 mg
      alfentanil (intravenously) were administered. This produced anaesthesia up to T8
      without any respiratory or cardiovascular embarrassment. A healthy male infant
      (Apgar score 9/10/10) was delivered. Postoperative analgesia was provided by
      intrathecal injections of bupivacaine and intravenous injections of piritramide.
      There were no intraoperative or postoperative problems. DISCUSSION: By means of
      continuous spinal anaesthesia for caesarean section it is possible to avoid
      typical complications of general anaesthesia (hypoxia, airway management,
      aspiration, tachycardia), of single-shot spinal anaesthesia (hypotension, low or
      high block) and of epidural anaesthesia (high dose of local anaesthetics, danger
      of accidental intrathecal or intravenous injection). The possibility of
      postoperative analgesia is advantageous. Technical difficulties, postspinal
      headache and the high costs of the sets may be disadvantageous. CONCLUSION: This
      case demonstrates, that the use of a continuous spinal catheter technique for
      caesarean section anaesthesia is an alternative method, which should be
      considered especially in high risk patients, when meticulous care for constant
      vital functions is requested urgently.

PMID- 9770095
TI  - [Weaning from artificial respiration. 2].

PMID- 9770096
TI  - The role of computerized video imaging in predicting adult extraction treatment
      outcomes.
AB  - The purpose of this study was to evaluate the accuracy of computerized video
      imaging in predicting the soft tissue outcome of extracting four premolars in
      adults. The pretreatment and posttreatment cephalometric and facial photographic
      records of 31 previously treated, nongrowing patients were digitized and computer
      generated cephalometric VTOs and video images were compared with the known
      outcomes. The results showed that both the VTOs and video images were accurate
      enough to be used for patient education and communication, as well as for
      diagnosis and treatment planning. While lay people found that the predicted video
      images adequately resembled the actual outcomes, orthodontists were more
      critical, particularly of the lower lip area where variable soft tissue responses
      to treatment were noted.

PMID- 9770097
TI  - An evaluation of two VTO methods.
AB  - A sample of 34 growing Class II patients was used to assess the reliability of
      manual and computer-generated visual treatment objectives (VTOs) when compared
      with the actual treatment results. Skeletal, dental, and soft tissue measurements
      were performed on the VTO and on the posttreatment tracings. Using paired t-tests
      and Pearson correlation coefficients, comparisons were made between the VTO and
      posttreatment tracings. Both the manual and computer VTO methods were accurate
      when predicting skeletal changes that occurred during treatment. However, both
      methods were only moderately successful in forecasting dental and soft tissue
      alterations during treatment. Only slight differences were seen between the
      manual and computer VTO methods, with the computer being slightly more accurate
      with the soft tissue prediction. However, the differences between the two methods
      were not judged to be clinically significant. Overall, the prediction tracings
      were accurate to only a moderate degree, with marked individual variation evident
      throughout the sample.

PMID- 9770098
TI  - Mandibular morphology in subjects with Class III malocclusions: Finite-element
      morphometry.
AB  - The absence of physical restraint may be associated with a mandibular allometry
      that contributes to mandibular prognathism. Cephalographs of 73 prepubertal
      children of European American descent with untreated Class III malocclusions were
      traced and eight mandibular landmarks digitized. The resulting eight-noded
      geometries were normalized, and the mean Class III geometry compared with the
      equivalent Class I average. Procrustes analysis established statistical
      difference (p < 0.05) between these mean configurations. A color-coded finite
      element (FEM) analysis was used to localize differences in morphology. Comparing
      Class III and normal mandibular configuration for changes in size, FEM revealed
      positive allometry of the mandibular corpus and around supramentale (15% increase
      in size), with reductions (30%) between the incisor alveolus and menton. For
      changes in shape, mandibular configurations were predominantly isotropic, with
      the exception of the anisotropic anterior region in the Class III subjects.
      Incremental growth differences are consistent with the view that the absence of
      physical restraint is associated with mandibular prognathism.

PMID- 9770099
TI  - Electromyographic investigation of chin cup therapy in Class III malocclusion.
AB  - Electromyographic activity was evaluated in 20 patients (10 girls and 10 boys,
      mean age 10 years) with Class III malocclusion who were treated with a chin cup
      appliance. The posttreatment data were obtained at the end of phase 1 chin cup
      treatment when the anterior crossbite had been corrected. EMG activity of the
      masseter and temporal muscles for each subject were studied during unilateral
      chewing using the following parameters: mean cumulative voltage (MCV), mean
      maximum peak voltage (MMPV), and rotational direction of the differential
      lissajous EMG (DL-EMG). The ANB angle improved from -1.0 degree (mean) to 0
      degree. The electromyographic study revealed a decrease in masseter muscle
      activity on both the working (chewing) and balancing sides, with no improvement
      in the coordination of bilateral masseter and anterior temporal muscles.

PMID- 9770100
TI  - Case report KY: functional analysis of a follow-up chin cup patient with TMJ
      pain.
AB  - At 19 years 1 month, the patient returned to the clinic for a follow-up screening
      of chin-cup patients. She was the only TMJ dysfunction patient who agreed to
      undergo further treatment. Mandibular kinesiograph, computer-aided axiograph, and
      electromyograph records were gathered to aid in evaluating function. Splint
      therapy and orthodontic retreatment relieved the TMJ pain associated with
      balanced muscular activity and helped to achieve more normal movement of the
      mandible.

PMID- 9770101
TI  - Longitudinal changes in Class I subjects with moderate mandibular skeletal
      protrusion.
AB  - Two groups of Class I females were followed from 6 to 18 years of age. At the
      initial evaluation, subjects in one group had normal sagittal jaw-base
      relationships, while those in the other group had moderate mesial relationships
      between the jaw bases. The purpose of this study was to compare craniofacial
      morphology and growth in these two groups. Subjects with mesial jaw-base
      relationships had mandibular skeletal protrusion due to a more forward
      positioning of the mandible relative to anterior cranial base. Other
      morphological group differences involved jaw-base relationships (but not jaw
      size). All the observed group differences were present at age 6; no new
      differences were observed later. Some differences stayed significant up to age
      18, while others became less distinct with time. Incremental growth in the groups
      was comparable. Similar growth of the jaws apparently helped to maintain initial
      group differences in jaw-base relationships.

PMID- 9770102
TI  - Occlusal outcome of orthodontic treatment.
AB  - The aim of this study was to evaluate the overall quality of orthodontic
      treatment in a university clinic. Dental casts of 1870 patients (799 males and
      1071 females) were evaluated at the pretreatment and posttreatment stages using
      the PAR index. The mean age was 13 +/- 4.1 years at the pretreatment stage and 16
      +/- 3.9 years at the posttreatment stage. At both stages, mean and standard
      deviations of the (weighted) PAR scores were calculated, along with the
      percentage reductions in the weighted PAR scores. The percentage of perfect
      scores (score = 0) of the different components of the PAR index was calculated.
      The analysis of variance and t-test were used to compare quality of treatment for
      the variables of treatment period and gender, respectively. The mean weighted PAR
      scores were 27.6 +/- 10 and 7.7 +/- 6.1 for the pretreatment and posttreatment
      models, respectively. The mean percentage improvement was 68.9%. The mean
      treatment duration was 3.0 +/- 1.4 years. Great improvement was noted in 42.8% of
      the sample, while 49.1% of the sample showed moderate improvement, and 8.3%
      either did not improve or became worse. The improvement of the PAR score at the
      posttreatment stage could, to some extent, be explained by the treatment period:
      The more recent the period the better the quality.

PMID- 9770103
TI  - Genetic influence on dental arch form in orthodontic patients.
AB  - Human arch form varies considerably. This study analyzed the size and shape of
      the maxillary and mandibular dental arches of 320 adolescents from 155 sibships.
      A broad battery of measurements (k = 48) was computer-generated from Cartesian
      coordinates of cusp tips and line angles of the permanent teeth, and heritability
      estimates were generated from intraclass correlations, controlling for sex and
      age where indicated. Arch size has a modest genetic component, on the order of
      50%, although this estimate may contain shared environmental influences. Tooth
      rotations have low h2 estimates, most of them indistinguishable from zero. Arch
      shape, assessed as length-width ratios, also has a modest transmissible
      component, suggesting that arch length and width growth factors are largely
      independent. Highest heritability estimates, as a group, were for transverse arch
      widths, which averaged about 60%. Several measures of left-right asymmetry also
      were analyzed (k = 31), and, while the arches are systematically asymmetric
      (generally with left > right), there is only weak evidence of a transmissible
      component for directional asymmetry and essentially none for fluctuating
      asymmetry. In all, arch size and shape are seen to be more subject to
      environmental influences than to heredity. These findings direct attention toward
      the need to better understand what extrinsic factors modulate arch size and shape
      during development.

PMID- 9770104
TI  - Mandibular lateral incisor-canine transposition, concomitant dental anomalies,
      and genetic control.
AB  - Mandibular lateral incisor-canine (Mn.I2.C) transposition is a rare developmental
      disturbance of tooth order characterized by positional interchange of the two
      teeth. In children with Mn.I2.C anomaly, the mandibular lateral incisor shows
      distal ectopic eruption and the adjacent canine subsequently erupts mesial to it.
      A sample of 60 orthodontic patients with Mn.I2.C transposition was studied using
      roentgenograms taken at the time of diagnosis. Two age-related phenotypes of the
      anomaly were identified: early-stage (median age, 9 years) and mature-stage
      (median age, 12 years). Mn.I2.C transposition occurred bilaterally in 10 subjects
      (17%) and favored female expression (sex ratio, M1:F3) and right-side occurrence
      (68% of unilateral cases). Statistically significant associations were found
      between Mn.I2.C transposition and increased frequency of tooth agenesis (M3, p <
      0.01; MnP2, p < 0.01) and peg-shaped maxillary lateral incisors (p < 0.0001). The
      results from this study and the analysis of 50 previously published cases provide
      evidence that Mn.I2.C transposition is a disturbance of tooth order and eruptive
      position probably caused by genetic influences. The Mn.I2.C anomaly likely
      results from genetic mechanisms similar to those responsible for occurrences of
      its associated dental anomalies, such as tooth agenesis and peg-shaped maxillary
      lateral incisors. In an appendix, clinical orthodontic management of Mn.I2.C
      transposition is discussed, based on treatment data derived from the study
      sample.

PMID- 9770105
TI  - A genetic study of anteroposterior and vertical facial proportions using model
      fitting.
AB  - Genetic model-fitting was used to determine the heritability of anteroposterior
      and vertical facial proportions in twins. Lateral headplates of 33 monozygotic
      and 46 dizygotic twins, none of whom had undergone orthodontic treatment, were
      used. Five proportions, based on four vertical and five horizontal measurements,
      were assessed: lower facial height, anterior- to posterior-facial height, total
      facial height to face depth, sella-A-point to sella-B-point, and sella-upper
      incisal edge to sella-lower incisal edge. Reproducibility was high for all
      variables. Model-fitting indicated that all the facial proportions were
      controlled by additive genes and the specific environment. The genetic component
      was 71% for upper-to lower-facial height, 66% for anterior- to posterior-facial
      height, 62% for total facial height, and 66% for sella-A-point to sella-B-point
      and sella-upper incisal edge to sella-lower incisal edge.

PMID- 9770106
TI  - Tooth rotation associated with aplasia of nonadjacent teeth.
AB  - The prevalence of tooth rotation concomitant with aplasia of nonadjacent teeth in
      uncrowded, nonsyndromic subjects was assessed. The sample consisted of 1620
      subjects (mean age 14 years 9 months). The findings were compared with the
      prevalence calculated for a matched control group of 1000 subjects. Rotation of
      maxillary lateral incisors in subjects with premolar aplasia and rotation of
      premolars in subjects presenting with maxillary lateral incisor aplasia were
      studied. Associations between both tooth position anomalies and tooth aplasia
      were significant (p < 0.01). In addition, the presence of rotated maxillary
      lateral incisors was also associated with aplasia of the homologous tooth on the
      opposite side of the dental arch; the same result was found for premolars. These
      data suggest a genetic component in the etiology of tooth malpositions, such as
      tooth rotation, which may be considered a covariable in a complex of genetically
      controlled dental disturbances, including tooth aplasia.

PMID- 9770108
TI  - [39th National Congress of Anesthesia and Resuscitation. Paris, France, 25-28
      September 1997. Abstracts].

PMID- 9770107
TI  - Canine transposition in prehistoric Pakistan: Bronze Age and Iron Age case
      reports.
AB  - This report documents two prehistoric cases of canine-first premolar
      transposition (Mx.C.P1) from the Indo-Pakistan subcontinent. Recent discussion of
      the etiology of canine transposition and reports of high prevalence for the
      condition in modern India accentuate the significance of the ancient cases
      reported there. Case 1 is from the Iron Age site of Sarai Khola in northern
      Pakistan (1000 BC). The specimen, an adult female, 25 to 30 years of age at
      death, exhibits unilateral Mx.C.P1 transposition on the left side. The condition
      is associated with a barrel-shaped maxillary left third molar in an otherwise
      normal and healthy maxillary dental arch. Case 2 is from the Bronze Age urban
      site of Harappa (2500 BC), an important center of the Indus Valley Civilization.
      In this specimen, an adult female, transposition is bilateral, resulting in
      displacement of premolars and large diastemata between the maxillary lateral
      incisors and first premolars. Bilateral agenesis of maxillary third molars and
      rotation of maxillary and mandibular teeth occur with transposition in this
      specimen. In neither case are the lateral incisors reduced in size, peg-shaped,
      or congenitally absent. This report of Mx.C.P1 transposition in prehistoric times
      is significant because it provides historical documentation for the female
      predilection of the trait and establishes its co-occurrence with specific dental
      variants, such as agenesis, reduction, and rotation of teeth.

PMID- 9770109
TI  - New targets, drugs, and approaches for the treatment of cancer: an overview.

PMID- 9770110
TI  - An old paradigm for treating cancer and other diseases in the 21st century.

PMID- 9770111
TI  - Monoclonal antibodies targeting the VEGF receptor-2 (Flk1/KDR) as an anti
      angiogenic therapeutic strategy.
AB  - Biological evidence suggests that interference with the function of the
      angiogenic growth factor receptor VEGFR2 (flk1/KDR) is a particularly promising
      strategy to inhibit tumor-induced angiogenesis. Proof of concept was established
      by developing a monoclonal rat anti-mouse VEGFR2 antibody (DC101) and showing
      that it potently blocked the binding of VEGF to its receptor, inhibited VEGF
      induced signaling, and strongly blocked tumor growth in mice through an anti
      angiogenic mechanism. Since DC101 does not cross-react with the human VEGFR2 KDR,
      anti-KDR monoclonal antibodies were generated by standard hybridoma technology
      and by using phage display library. High affinity antibodies (Kd = 4.9 x 10(-10)
      1.1 x 10(-9) M) were found with both approaches. The anti-KDR antibodies compete
      on an equimolar basis with VEGF for binding to KDR and inhibit with similar
      potency the VEGF-induced signaling and mitogenesis in human endothelial cells.
      Although these antibodies cannot be tested for in vivo efficacy in standard
      murine tumor models because of lack of species cross-reactivity, the similarity
      of their in vitro properties with those of DC101 suggests that they may be
      effective in blocking KDR function in vivo.

PMID- 9770112
TI  - PSC-833, a frontier in modulation of P-glycoprotein mediated multidrug
      resistance.
AB  - The expression of drug efflux mechanisms by cancer cells during chemotherapy
      leads to multidrug resistance (MDR) and constitutes a major obstacle in the
      effective treatment of cancer. The most widely characterized drug effluxes pump
      is P-glycoprotein (P-gp) and efforts are being directed towards identifying
      agents that reverse P-gp mediated drug resistance. PSC-833 is a non
      immunosuppressive cyclosporin derivative that potently and specifically inhibits
      P-gp. The current review focuses on the elucidation of the mechanism of action of
      PSC-833 as a potential MDR reversing agent, using syngeneic multidrug resistant
      sublines of MDA435 human breast adenocarcinoma cell line that express increasing
      levels of P-gp. In vitro experiments indicate that PSC-833 interacts directly
      with P-gp with high affinity and probably interferes with the ATPase activity of
      P-gp. Studies in multidrug resistant tumor models confirm P-gp as the in vivo
      target of PSC-833 and demonstrate the ability of PSC-833 to reverse MDR leukemias
      and solid tumors in mice. Presently, PSC-833 is being evaluated in the clinic.

PMID- 9770113
TI  - Antisense comes of age.
AB  - During the last ten years, antisense technology has experienced growing pains not
      unlike those of adolescence. In 1992, antisense was trumpeted as one of the top
      10 emerging research areas. However, 3 years later, researchers were confronted
      with significant problems associated with antisense oligonucleotides ranging from
      sequence-dependent, non-antisense effects in vitro to dose-limiting toxicities in
      preclinical models [1-3]. Many researchers had doubts whether sequence-specific
      antisense even existed or whether it would ever exist as a therapeutic strategy
      [4]. Despite these gloomy predictions, many of the challenges facing the
      development of antisense-based drugs as therapeutics have been overcome as
      evidenced by the progress of several antisense oligonucleotides in the clinic for
      the treatment of cancer.

PMID- 9770114
TI  - Anti-adhesion cancer therapy.

PMID- 9770115
TI  - The molecular basis of the hypoxia response pathway: tumour hypoxia as a therapy
      target.
AB  - Hypoxia induces a cascade of physiological responses that includes glycolysis,
      erythropoiesis, angiogenesis, changes in adrenergic signal transduction and
      vascular cellular proliferation. Hypoxia-inducible genes are relevant to growth
      and behaviour of cancer as well as the adaptation and survival of normal tissues.
      Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric DNA binding complex
      composed of two basic-helix-loop-helix PAS-proteins: HIF-1 beta/ARNT (aryl
      hydrocarbon receptor nuclear translocator), which is constitutively expressed,
      and HIF-1 alpha, which is not present in normoxic cells but induced under hypoxic
      conditions. Recently another member of the bHLH-PAS family, EPAS-1 has been
      reported and shares similar properties with HIF-1 alpha, although it is
      considered endothelial specific. In addition, the presence of other DNA-binding
      motifs in the promoter of hypoxia-inducible genes highlight the occurrence of
      cross-talk between transcription factors in the modulation of hypoxic gene
      expression. In this review, we present a survey of the hypoxia response pathway
      and we discuss attempts to use gene therapy activated by the low oxygen
      environment or by necrotic regions of tumours.

PMID- 9770116
TI  - The erbB2 gene as a cancer therapeutic target and the tumor- and metastasis
      suppressing function of E1A.

PMID- 9770117
TI  - Pre-clinical development of farnesyltransferase inhibitors.
AB  - ras is the oncogene most frequently found in human cancers, being detected in 30%
      of most human cancers and at significantly higher rates in certain cancers
      including pancreatic (90%) and colon (50%) [1]. Almost 10 years ago it was shown
      that a C-terminal lipid modification of Ras, catalyzed by a specific farnesyl
      protein transferase (FPTase), was required for the function of both normal and
      oncogenic Ras proteins. This finding spurred the development of FPTase inhibitors
      (FTIs) as a potential cancer therapy directed at the ras oncogene. FTIs have
      exhibited potent antiproliferative activity in cell culture and animal tumor
      models with a surprising lack of toxicity to normal tissues. However, while FTIs
      were originally conceptualized as Ras-specific agents, their mechanism of action
      is significantly more complicated than originally envisioned.

PMID- 9770118
TI  - Future developments in the selectivity of anticancer agents: drug delivery and
      molecular target strategies.
AB  - In the past, our limited understanding of the processes involved in the
      initiation and growth of cancer hindered our ability to effectively treat most
      human malignancies and therapies were often associated with significant toxic
      side effects as well as re-emergence of disease. The development of drug delivery
      systems such as liposomes has improved the specificity of various conventional
      anticancer agents by enhancing drug accumulation in tumors while often decreasing
      exposure to susceptible healthy tissues. More recently, the identification of a
      wide range of genes and corresponding protein products that are altered in
      various human cancers has revealed new molecular targets for cancer therapy that
      may provide improved selectivity for tumor cells over traditional cytotoxic
      agents. This review discusses how advances in the sophistication of liposomal
      delivery systems may open new opportunities for combining novel molecular
      targeting strategies with pharmacological targeting via liposomes to optimize the
      therapy of many human malignancies.

PMID- 9770119
TI  - Targeting DNA methyltransferase in cancer.
AB  - DNA methyltransferase is an enzyme responsible for generating and maintaining DNA
      methylation patterns. DNA methylation patterns control different genome
      functions, thus they are an important component of the epigenetic information. It
      has been recently postulated that DNA methyltransferase plays an important role
      in oncogenesis and that it is a candidate target for anticancer therapy. This
      commentary discusses the possible mechanisms through which DNA methyltransferase
      participates in oncogenesis and the rationale for targeting it in cancer.

PMID- 9770120
TI  - Inhibition of apoptotic signaling pathways in cancer cells as a mechanism of
      chemotherapy resistance.
AB  - The extracellular microenvironment of tumors differs from most normal tissues.
      Many tumors have relatively acidic extracellular pH (pHe), although the
      intracellular pH (pHi) of tumor cells remains normal due to efficient maintenance
      of a large proton gradient across the membrane. This difference between tumors
      and normal tissues might be exploited therapeutically by disruption of the
      mechanisms which regulate pHi, so that tumor cells are killed by intracellular
      acid-induced injury. To investigate the mechanisms by which intracellular
      acidification leads to cell death, we have studied the roles of the anti
      apoptotic gene bcl-2 and its pro-apoptotic binding partner bax, the Stress
      Activated Protein Kinases (SAPK/JNK), and the caspase proteases in mediating acid
      induced cell death. While expression of bcl-2 in human bladder cancer MGH-U1
      cells had no effect on acid-induced death, overexpression of bax enhanced cell
      death, consistent with its pro-apoptotic function. Inhibition of SAPK, through
      expression of a dominant negative mutant of its activator, SEK1 protected cells
      from acid-induced cell death. Caspase activation, as measured by poly (ADP
      ribose) polymerase cleavage, was absent after lethal intracellular acidification.
      Consistent with this observation, inhibition of ICE proteases by the peptide z
      VAD.fmk did not protect against acid-induced cell killing. We conclude that acid
      induced cell death depends on bax and on SAPK signaling pathways but not on the
      caspase proteases. Therapeutic manipulation of bax and SAPK may enhance acid
      induced tumor cell killing.

PMID- 9770121
TI  - The pivotal role of VEGF in tumor angiogenesis: molecular facts and therapeutic
      opportunities.

PMID- 9770123
TI  - The safety of pramoxine hydrochloride when used as a topical (surface)
      anesthetic.

PMID- 9770122
TI  - Geographical considerations regarding donor leukocyte infusions for the treatment
      of relapsed hematological malignancies.
AB  - Infusion of donor leukocytes, to provoke graft-versus-host disease and a graft
      versus leukemia effect, is remarkably effective in the treatment of some forms of
      relapsed hematological malignancies after transplantation of allogeneic stem
      cells. In this commentary I argue that the variable susceptibility of tumor cells
      to donor leukocyte infusions can be predicted on the basis of their localization
      to the T cell areas of secondary lymphoid organs and the amount of donor
      chimerism in the patient. This conclusion leads to the hypothesis that it may be
      possible to modulate graft-versus-leukemia reactions in a controlled and
      predictable fashion.

PMID- 9770124
TI  - Aquatic adversaries: human injuries induced by octopi.

PMID- 9770125
TI  - "Intradermal testing and sublingual desensitization for nickel".

PMID- 9770126
TI  - Childhood onychomycosis: alternariosis of all ten fingernails.

PMID- 9770127
TI  - Apoptosis with positive direct immunofluorescence findings in a patient with
      necrolytic migratory erythema.
AB  - A 45-year-old man with a glucagonoma and necrolytic migratory erythema is
      described. Clinical, radiographic, and histologic features were typical for this
      syndrome. However, a skin biopsy specimen for direct immunofluorescence
      examination revealed apoptotic keratinocytes that stained positive with
      immunoglobulins, fibrinogen, and C3. These immunofluorescence findings were
      initially interpreted erroneously as showing erythema multiforme or a related
      disorder. We present a unique case of necrolytic migratory erythema with positive
      direct immunofluorescence findings reflecting immunoglobulin and complement
      deposition within dyskeratotic epithelial cells.

PMID- 9770128
TI  - Keratoderma with pseudo-Quincke's pulse.
AB  - The physical examination sign known as Quincke's capillary pulse is elicited by
      pressing lightly on the distal edge of a fingernail. When the vasculature of the
      nailbed is partly blanched, Quincke's pulse appears as alternating flashes of red
      and white that reveal arterial pulsations. This sign is seen in many normal
      persons, but it is most prominent in individuals with widened pulse pressures,
      such as aortic insufficiency. This case report describes a patient with
      keratoderma and sclerodactyly whose fingernails exhibited rapid color changes,
      mimicking Quincke's pulse. The visible pulsations were due to sclerodactylous
      compression of the nailbeds, and not to any primary hemodynamic process.

PMID- 9770129
TI  - Erythema multiforme associated with contact dermatitis to poison ivy: three cases
      and a review of the literature.
AB  - Erythema multiforme (EM) is a hypersensitivity reaction that occurs mainly after
      exposure to certain medications or in the setting of infection, most commonly
      that due to herpes simplex virus. Rare cases of EM have been reported after
      allergic contact dermatitis due to various substances. There has been one case in
      the literature of EM following Rhus contact dermatitis. We report three patients
      who developed EM after allergic contact dermatitis due to poison ivy. In all
      three patients, targetoid lesions developed primarily on the palms and soles,
      either after a brief course of prednisone or during its taper. Two of the
      patients have had more than one episode of EM after poison ivy dermatitis.
      Although EM has been described after allergic contact dermatitis due to a variety
      of antigens (nickel being the most common), there is only one report in the
      literature of EM following Rhus contact dermatitis. Given the prevalence of
      allergic contact dermatitis due to poison ivy, this may be an under-reported
      complication.

PMID- 9770130
TI  - Recurrent malignant melanoma presenting with zosteriform metastases.
AB  - A 63-year-old man with recurrent metastatic malignant melanoma presented with a
      painful right twelfth thoracic dermatomal eruption initially thought to be herpes
      zoster. However, 3 weeks later, the patient clearly had melanoma skin metastases
      confined exclusively to this dermatome. Radiotherapy and opiate analgesics
      provided effective pain relief. We propose that in this patient, no herpes zoster
      infection occurred, but rather that skin metastases presented in a zosteriform
      pattern due to lymphatic spread from a previously excised paravertebral skin
      metastasis. This is the second reported case of malignant melanoma presenting as
      zosteriform metastases, and we suggest physicians consider this possibility in
      patients with melanoma presenting with dermatomal skin changes.

PMID- 9770131
TI  - Granular cell tumor of the toe.
AB  - A 33-year-old black woman with an unusual case of a solitary granular cell tumor
      (GCT) involving the toe is presented, as is a review of the literature. The
      clinical presentation, histopathologic appearance, differential diagnosis, and
      treatment of solitary granular cell tumors are discussed. GCTs are uncommon
      tumors and are thought to be of Schwann cell origin. These tumors usually present
      as reddish-brown to flesh-colored papules that are occasionally tender or
      pruritic. The surface is usually smooth, but may be ulcerated or verrucous.
      Although they are usually solitary, they may be multiple. These tumors are almost
      always benign, but malignant variants have been reported. Predilection is
      greatest in females, and blacks are affected several times more often than
      whites. The skin overlying the face, trunk, fingers, and mucous membranes account
      for the vast majority of reported cases.

PMID- 9770132
TI  - Acquired secondary syphilis in a 6-year-old girl with no history of sexual abuse.
AB  - A case of secondary syphilis acquired by nonsexual household contact in a
      prepubertal girl is presented.

PMID- 9770133
TI  - Small colony variants in staphylococcal infections: diagnostic and therapeutic
      implications.
AB  - The discovery of S. aureus small colony variants as persistent and intracellular
      has provided new insight into the understanding of pathogenesis associated with
      staphylococcal diseases. Survival advantages are afforded to SCVs on the basis of
      their ability to hide within host cells, which provide protection from the immune
      system and some antibiotics. In addition, because most clinical SCVs are
      defective in electron transport, their uptake of positively charged antimicrobial
      substances is reduced. The atypical clinical microbiologic characteristics make
      identification and susceptibility testing difficult. SCVs have been recovered
      from patients with unusually persistent infections, particularly those patients
      with long disease-free intervals, and from patients who are chronically exposed
      to aminoglycosides and TMP-SMZ, suggesting that these clinical situations are
      those in which SCVs should be suspected and the clinical laboratory should
      carefully search for them.

PMID- 9770134
TI  - Human granulocytic ehrlichiosis in Europe: clinical and laboratory findings for
      four patients from Slovenia.
AB  - Febrile illnesses following a tick bite in patients from Slovenia were evaluated
      for an ehrlichial etiology. A case of acute human granulocytic ehrlichiosis (HGE)
      was confirmed by seroconversion to the HGE agent or molecular identification of
      ehrlichial organisms. Acute infection with the HGE agent was confirmed in four
      patients. None of the patients had detectable antibodies to the HGE agent at
      their first visit, but polymerase chain reaction analysis was positive for three
      patients. All four patients subsequently seroconverted to the HGE agent as shown
      by high titers of antibody. Clinical features and laboratory findings were
      similar to those in reports from the United States, although the disease course
      was relatively mild in the Slovenian cases. All patients recovered rapidly and
      without sequelae, although only two received antibiotic therapy (of whom only one
      was treated with doxycycline). HGE is an emerging tick-borne disease in the
      United States and should now be included in the differential diagnosis of febrile
      illnesses occurring after a tick bite in Europe.

PMID- 9770135
TI  - Photo quiz. Loiasis.

PMID- 9770136
TI  - Numerous eruptive lesions of panniculitis associated with group A streptococcus
      bacteremia in an immunocompetent child.
AB  - A previously healthy 13-month-old boy developed group A beta-hemolytic
      streptococcus bacteremia coinciding with numerous eruptive subcutaneous lesions
      primarily on his extremities. Skin biopsy revealed infectious panniculitis; gram
      positive cocci were present within both fat lobules and septa. Molecular genetic
      analysis of an isolate from the patient's blood revealed an emm type 4 organism
      displaying the emm chromosomal pattern E that is characteristic of opacity factor
      producing strains; the organism also harbored the gene encoding for streptococcal
      pyrogenic exotoxin C (speC). To our knowledge, this clinical presentation has not
      yet been described in the spectrum of infections directly caused by group A beta
      hemolytic streptococci.

PMID- 9770137
TI  - Infections due to sandfly fever virus serotype Toscana in Spain.
AB  - Of the sandfly fever viruses known to be human pathogens (serotypes Toscana
      [TOS], Sicilian [SFS], and Naples [SFN]), only TOS has demonstrated neurotropic
      activity. Infections by TOS have been reported in Mediterranean countries, but
      the virus was previously isolated only in Italy and Portugal. We isolated 15
      strains of TOS between 1988 and 1996 from the cerebrospinal fluid of patients
      with acute aseptic meningitis in Granada, Spain. This finding led us to study the
      presence of antibodies to TOS, SFS, and SFN in 1,181 adults and 87 children from
      different regions of Spain. We found that the prevalence of antibodies to these
      viruses was 26.2%, 2.2, and 11.9%, respectively; these rates imply that TOS
      infections are common in Spain.

PMID- 9770139
TI  - Primary cutaneous aspergillosis--an emerging infection among immunocompromised
      patients.

PMID- 9770138
TI  - Invasive pulmonary aspergillosis in a critically ill neonate: case report and
      review of invasive aspergillosis during the first 3 months of life.
AB  - We report a fatal case of invasive pulmonary aspergillosis in a severely ill
      neonate and review 43 additional cases of invasive aspergillosis reported from
      1955 through 1996 that occurred during the first 3 months of life. Eleven of the
      44 patients had primary cutaneous aspergillosis, 10 had invasive pulmonary
      aspergillosis, and 14 had disseminated disease. Most infections were nosocomial
      in origin. Prematurity (43%); proven chronic granulomatous disease (14%); and a
      complex of diarrhea, dehydration, malnutrition, and invasive bacterial infections
      (23%) accounted for the majority of underlying conditions. At least 41% of the
      patients had received corticosteroid therapy before diagnosis, but only one
      patient had been neutropenic. Among patients who received medical and/or surgical
      treatment, outcome was relatively favorable, with an overall survival rate of
      73%. Invasive aspergillosis may occur in neonates and young infants and warrants
      consideration under certain circumstances. Current therapeutic approaches consist
      of high-dose amphotericin B and appropriate surgical interventions.

PMID- 9770140
TI  - Is bacterial tracheitis changing? A 14-month experience in a pediatric intensive
      care unit.
AB  - Bacterial tracheitis is characterized by acute upper-airway obstruction and
      purulent secretions within the trachea. Historically, affected children were
      young, stridorous, and toxic-appearing and required tracheal intubation, and
      morbidity and mortality were significant. Staphylococcus aureus was the most
      common organism involved. During the 14 months of this retrospective study, 46
      children were admitted to the pediatric intensive care unit because of this
      diagnosis, and their medical records were reviewed. Compared with those in
      previous reports, children in this study were older (mean +/- standard error of
      the mean [SEM], 69.3 +/- 6.8 months) and less toxic. Only 26 (57%) of 46 patients
      required tracheal intubation. Intubated patients were significantly younger than
      nonintubated patients (mean +/- SEM, 46.9 +/- 6.5 vs. 98.9 +/- 9.9 months).
      Moraxella catarrhalis was identified in 12 (27%) of 45 bacterial respiratory
      cultures, while influenza A virus was recovered from 18 (72%) of 25 viral
      respiratory cultures. There were no major complications. This series represents
      the largest reported cohort of patients with this condition and suggests an
      epidemiological change toward a less morbid condition.

PMID- 9770141
TI  - Nosocomial sinusitis in patients in the medical intensive care unit: a
      prospective epidemiological study.
AB  - A prospective observational cohort study of nosocomial sinusitis was carried out
      in two medical intensive care units. Sinusitis was diagnosed by computed
      tomographic scanning and the culture of sinus fluid obtained by puncture of a
      maxillary sinus. Clinical and epidemiological data were collected at the time of
      admission to the unit and daily thereafter. Specimens from the nares, oropharynx,
      trachea, and stomach were cultured on admission and daily thereafter. The
      cumulative incidence of nosocomial sinusitis was 7.7%, and the incidence rates
      were 12 cases per 1,000 patient-days and 19.8 cases per 1,000 nasoenteric tube
      days. Risk factors for nosocomial sinusitis, as determined by multiple logistic
      regression analysis, included nasal colonization with enteric gram-negative
      bacilli (odds ratio [OR], 6.4; 95% confidence interval [95% CI], 2.2-18.8; P =
      .007), feeding via nasoenteric tube (OR, 14.1; 95% CI, 1.7-117.6; P = .015),
      sedation (OR, 15.9; 95% CI, 1.9-133.5; P = .011), and a Glasgow coma score of <
      or = 7 (OR, 9.1; 95% CI, 3.0-27.3; P = .0001).

PMID- 9770142
TI  - Entamoeba gingivalis in human immunodeficiency virus type 1-infected patients
      with periodontal disease.
AB  - Necrotic periodontal disease is a progressive painful oral lesion in human
      immunodeficiency virus type 1 (HIV-1)-infected patients, and the etiology is
      unknown. Earlier studies of HIV-1-infected patients have shown significant
      changes in the viral and fungal oral microflora. The aim of this study was to
      relate the occurrence of protozoa to clinical symptoms and immunosuppression.
      Oral symptoms were registered in 45 patients at different stages of the HIV-1
      infection and in 15 HIV-seronegative healthy controls. Saliva and dental plaque
      were analyzed for the presence of protozoa. Entamoeba gingivalis was the only
      protozoa found in the oral cavities of HIV-1-infected patients with periodontal
      disease. Its presence was not related to the degree of immunodeficiency but to
      the HIV diagnosis. This study describes for the first time the findings of E.
      gingivalis in the oral cavities of HIV-1 infected patients.

PMID- 9770143
TI  - Congenital tuberculosis in a neonatal intensive care unit: case report,
      epidemiological investigation, and management of exposures.
AB  - Disseminated tuberculosis was diagnosed at the autopsy of a 65-day-old premature
      infant who died in a 52-bed neonatal intensive care unit (NICU). Both parents and
      one sibling had previously had positive tuberculin skin tests (TSTs); none had
      active pulmonary tuberculosis, but a second sibling had hilar adenopathy.
      Congenital transmission was confirmed by isolation of Mycobacterium tuberculosis
      from the mother's endometrium and the infant's lung tissue. Both strains were
      identical by DNA restriction fragment analysis. TSTs were performed on 14
      neonates, 27 NICU visitors, 11 contacts of the family, and 260 health care
      workers. TST conversion occurred in two nurses (0.8%); both had normal chest
      radiographs and received isoniazid therapy. Exposed neonates had negative chest
      radiographs, had negative gastric aspirates for acid-fast bacilli, and received
      isoniazid preventive therapy. Diagnosis of congenital tuberculosis requires a
      high index of suspicion. Transmission of tuberculosis in the NICU setting is
      unusual but can occur.

PMID- 9770144
TI  - Outcome of Staphylococcus aureus bacteremia according to compliance with
      recommendations of infectious diseases specialists: experience with 244 patients.
AB  - To determine whether recommendations of infectious diseases specialists affect
      outcome for patients, we evaluated 244 hospitalized patients with Staphylococcus
      aureus bacteremia. We offered our management recommendations to each patient's
      physicians and then assessed the clinical outcome for both patients for whom our
      consultative advice was followed and those for whom our advice was not heeded.
      All patients were followed up for 12 weeks after their first positive blood
      culture. Our management advice was followed for 112 patients (45.9%) and
      partially or completely ignored for 132 patients (54.1%). Patients for whom our
      recommendations were followed were more likely to be cured of their S. aureus
      infection and less likely to relapse (P < .01), despite having significantly more
      metastatic infections (P < .01) at the outset of therapy, than were those for
      whom our recommendations were not followed. Failure to follow recommendations to
      remove an infected intravascular device was the most important risk for treatment
      failure. After controlling for other factors, logistic regression analysis
      revealed that patients whose intravascular device was not removed were 6.5 times
      more likely to relapse or die of their infection than were those whose device was
      removed. Our findings suggest that patient-specific management advice by
      infectious diseases consultants can improve the clinical outcome for patients
      with S. aureus bacteremia.

PMID- 9770145
TI  - Diarrhea and Clostridium difficile infection in Latin American patients with
      AIDS. Working Group on AIDS in Peru.
AB  - Diarrhea and wasting are among the most debilitating and deadly manifestations of
      AIDS, yet only limited information is available regarding the etiology, clinical
      consequences, and immunologic effects of infection with diarrheal agents.
      Peruvian AIDS patients presenting with and without diarrhea were followed
      prospectively to examine the relations among diarrheal pathogens, clinical
      presentations, CD4 lymphocyte count, weight loss, and survival. Patients with
      chronic diarrhea had lower CD4 lymphocyte counts (P = .001) and lost more weight
      (P < .001). Weight loss and a decreased CD4 lymphocyte count were associated with
      increased mortality (P = .011 and P = .003, respectively). Mean CD4 lymphocyte
      count varied significantly by diarrheal agent. Clostridium difficile was the most
      prevalent pathogen and was associated with significantly increased mortality
      before and after adjustment for coinfection, length of follow-up, CD4 lymphocyte
      count, and weight loss (P = .006). C. difficile may be a more important and more
      prevalent etiologic agent in AIDS than previously recognized and may represent a
      preventable cause of death in patients with immunosuppression.

PMID- 9770147
TI  - Total parenteral nutrition via multilumen catheters does not increase the risk of
      catheter-related sepsis: a randomized, prospective study.
AB  - The purpose of this study was to determine in a randomized, prospective manner
      whether administration of total parenteral nutrition (TPN) via multilumen
      catheters increases the risk of catheter-related sepsis (CRS). All patients
      receiving hyperalimentation during a 24-month period were randomized to receive
      either a double-lumen catheter (DLC) or a triple-lumen catheter (TLC). A total of
      101 catheters were placed in 79 patients, of which 49 were DLCs and 52 were TLCs.
      The patients with DLCs received a total of 784 days of TPN, whereas patients with
      TLCs received a total of 754 days of TPN. CRS was associated with one (2.0%) of
      the 49 DLCs vs. one (1.9%) of the 52 TLCs. In comparison, the rate of CRS
      associated with single-lumen catheters (historical control) at our institution
      was 1.4% (P > .90). We conclude that the use of multilumen catheters in TPN
      therapy does not result in an increased risk of CRS.

PMID- 9770146
TI  - Efficacy and safety of atovaquone/proguanil as suppressive prophylaxis for
      Plasmodium falciparum malaria.
AB  - Currently recommended prophylactic regimens for Plasmodium falciparum malaria are
      associated with a high incidence of adverse events and/or suboptimal efficacy. In
      a double-blind, placebo-controlled, randomized clinical trial in western Kenya,
      adult volunteers received a treatment course of atovaquone/proguanil
      hydrochloride (250 mg/100 mg per tablet) to eliminate preexisting infection.
      Immediately thereafter, subjects were randomized to one of the three prophylactic
      regimens to receive one atovaquone/proguanil tablet daily (n = 68), two
      atovaquone/proguanil tablets daily (n = 65), or placebo (n = 65) for 10 weeks.
      The study endpoint for any subject was the development of parasitemia, evident on
      blood smear, during prophylaxis. Of the evaluable subjects, all in the low-dose
      (54 of 54) and high-dose (54 of 54) atovaquone/proguanil groups remained malaria
      free during the 10-week prophylaxis period, in contrast to only 48% (26 of 54) in
      the placebo group (P < .001). Both atovaquone/proguanil prophylactic regimens
      were as well tolerated as placebo. Thus, atovaquone/proguanil appears to be
      highly efficacious and safe as prophylaxis for P. falciparum malaria.

PMID- 9770148
TI  - Microglial nodular encephalitis and ventriculoencephalitis due to cytomegalovirus
      infection in patients with AIDS: two distinct clinical patterns.
AB  - In patients with AIDS, cerebral infection due to cytomegalovirus (CMV) results in
      two distinct neuropathological patterns: microglial nodular encephalitis (MGNE)
      and ventriculoencephalitis (VE). In order to identify clinical features to
      facilitate the differential diagnosis of these two forms of CMV encephalopathy in
      living patients, we retrospectively reviewed the clinical records of 18 patients
      with MGNE or VE diagnosed at autopsy. We identified the following clinical
      features as distinguishing the two encephalopathies: (1) MGNE manifests earlier
      than VE; (2) the onset of MGNE is acute, whereas the onset of VE is insidious;
      (3) the onset of MGNE is marked by confusion and delirium, which do not occur in
      VE; (4) VE is frequently associated with radiculopathy, which is absent in MGNE;
      and (5) VE is associated with more marked alterations in cerebrospinal fluid
      (high protein levels and pleocytosis). The early neurological manifestations of
      MGNE should prompt a search for systemic CMV infection, which may lead to earlier
      treatment.

PMID- 9770149
TI  - Herpes zoster and lymphopenia associated with sodium stibogluconate therapy for
      cutaneous leishmaniasis.
AB  - A review of 84 patients with cutaneous leishmaniasis treated with sodium
      stibogluconate (Pentostam) at our institution revealed that three had developed
      herpes zoster during or shortly after receiving therapy. Because zoster has been
      associated with depressed cellular immunity, we prospectively followed serial
      lymphocyte subpopulations in eight patients with cutaneous leishmaniasis who
      received Pentostam. By day 7 of therapy, the white blood cell count had fallen by
      a median of 1.15/mm3, the total lymphocyte count by a median of 804/mm3, and the
      CD4+ lymphocyte count by a median of 306/mm3 (67% of baseline; confidence
      interval, 52%-78%). An in vitro cell-viability assay demonstrated that Pentostam
      is not toxic to human mononuclear cells. The administration of Pentostam for the
      treatment of cutaneous leishmaniasis results in lymphopenia that may be related
      to the subsequent occurrence of herpes zoster.

PMID- 9770150
TI  - Amniotic fluid defensins: potential markers of subclinical intrauterine
      infection.
AB  - Human neutrophil peptides 1-3 (defensins) are granule constituents released from
      activated neutrophils. We hypothesized that amniotic fluid (AF) defensin levels
      are elevated in preterm labor (PTL) patients with subclinical intrauterine
      infection (IUI). AF samples were obtained from 203 pregnant patients with varying
      clinical characteristics. Defensin levels were measured by enzyme-linked
      immunosorbent assay. Median AF defensin levels were fourfold to 24-fold higher in
      patients with IUI than in preterm and term controls. Among patients with
      subclinical IUI, the degree of AF defensin elevation was greater in those with a
      positive AF culture. AF defensin levels increased exponentially with increasing
      severity of histologic chorioamnionitis. An AF defensin level of > 2,500 ng/mL
      identified 88% of patients with a positive AF culture, whereas a level of > 400
      ng/mL identified 85% of all infected patients. AF defensin levels accurately
      identify patients with subclinical IUI, as defined by a positive AF culture or
      placental histology.

PMID- 9770151
TI  - Human coenurosis in North America: case reports and review.
AB  - Coenurosis is a zoonotic disease of humans caused by the larval stage of Taenia
      (Multiceps) species. In North America, the adult tapeworm of Taenia (Multiceps)
      serialis is found in canids. The cystic larval forms (coenuri) are found in
      hares, rabbits, squirrels, and, rarely, in humans. We review in clinical detail
      the fifth case reported from North America, involving a child with extensive
      central nervous system involvement. We also report a sixth case, involving an
      adult with an intramuscular coenurus. The latter case was diagnosed by needle
      aspiration of the cyst. Although praziquantel administration may have been
      effective in killing the parasite in both patients, we are concerned about the
      production of marked inflammation as a result of treatment. The four other North
      American cases are reviewed, and the epidemiology of the infection in animals is
      discussed.

PMID- 9770152
TI  - Clindamycin with primaquine vs. Trimethoprim-sulfamethoxazole therapy for mild
      and moderately severe Pneumocystis carinii pneumonia in patients with AIDS: a
      multicenter, double-blind, randomized trial (CTN 004). CTN-PCP Study Group.
AB  - This double-blind, randomized, multicenter trial compared clindamycin/primaquine
      (Cm/Prq) with trimethoprim-sulfamethoxazole (TMP-SMZ) as therapy for AIDS-related
      Pneumocystis carinii pneumonia (PCP). Forty-five patients received clindamycin
      (450 mg four times daily [q.i.d.]) and primaquine (15 mg of base/d); 42 received
      TMP-SMZ (320 mg/1,600 mg q.i.d. if weight of > or = 60 kg or 240 mg/1,200 mg
      q.i.d. if weight of < 60 kg) plus placebo primaquine. Overall, the efficacy of
      Cm/Prq was similar to that of TMP-SMZ (success rate, 76% vs. 79%, respectively);
      Cm/Prq was associated with fewer adverse events (P = .04), less steroid use (P =
      .18), and more rashes (P = .07). These differences were even greater for patients
      with PaO2 of > 70 mm Hg (P = .02, P = .04, and P = .02, respectively). For
      patients with PaO2 of < or = 70 mm Hg (23 Cm/Prq recipients and 21 TMP-SMZ
      recipients), the efficacy of Cm/Prq was similar to that of TMP-SMZ (success rate,
      74% vs. 76%, respectively); Cm/Prq was associated with similar adverse events (P
      = .57), steroid use (P = .74), and rashes (P = .78). This trial confirms that
      Cm/Prq is a reasonable alternative therapy for mild and moderately severe PCP.

PMID- 9770153
TI  - Use of hepatitis A vaccine in a community-wide outbreak of hepatitis A.
AB  - Hepatitis A outbreaks in communities are often difficult to control. From July
      1994 through June 1995, 676 cases of hepatitis A were reported in Shelby County,
      Tennessee. With the licensure of a hepatitis A vaccine in February 1995, a new
      tool for outbreak control became available. During August-October 1995, a mass
      vaccination campaign was conducted. A total of 34,054 children received the first
      dose of hepatitis A vaccine. From December 1995 through December 1996, the number
      of hepatitis A cases reported inside the intervention area declined by 64%;
      outside the intervention area, the number of cases declined by 40%. The precise
      contribution of the vaccine campaign to the decline in the number of outbreak
      cases is difficult to quantify because community outbreaks often wane over time.
      The vaccine campaign may have hastened the decline of the number of outbreak
      cases. Future interventions should consider an earlier campaign with greater
      vaccine coverage.

PMID- 9770154
TI  - Cryptosporidiosis in patients with AIDS: correlates of disease and survival.
AB  - Although 10%-15% of patients with AIDS in the United States may acquire
      cryptosporidium infection, little data exist on clinical or histological
      characteristics that differentiate clinical outcomes. A case-control study of 83
      HIV-positive adult patients with cryptosporidiosis was conducted, as was a
      histopathologic review of data on gastrointestinal biopsy specimens from 30
      patients. Four clinical syndromes were identified: chronic diarrhea (36% of
      patients), choleralike disease (33%), transient diarrhea (15%), and relapsing
      illness (15%). A multivariate analysis of data for cases and controls revealed
      that acquiring cryptosporidiosis was associated with the presence of candidal
      esophagitis (odds ratio [OR], 2.53; P < .002) and Caucasian race (OR, 6.71; P =
      .0001) but not with sexual orientation. Cases had a significantly shorter
      duration of survival from the time of diagnosis than did controls (240 vs. 666
      days, respectively; P = .0004), which was independent of sex, race, or or
      injection drug use. Antiretroviral use was protective against disease (OR, 0.072;
      P = .0001). All four clinical syndromes were represented among the histological
      data. There was no statistically significant correlation between histological
      intensity of infection and clinical severity of illness.

PMID- 9770155
TI  - Selective screening of carriers for control of methicillin-resistant
      Staphylococcus aureus (MRSA) in high-risk hospital areas with a high level of
      endemic MRSA.
AB  - Screening for methicillin-resistant Staphylococcus aureus (MRSA) carriage in
      patients at risk was evaluated as part of a control program in a 26-bed medical
      intensive care unit (ICU) of a university hospital with a high level of endemic
      MRSA. Control measures included isolation and barrier precautions, skin
      decolonization with chlorhexidine of patients from whom MRSA was recovered, and
      mupirocin treatment of nasal carriers of MRSA. Of 3,686 patients admitted during
      a 4-year period, 44% were screened, which occurred during admission for 38%; MRSA
      was recovered from 293 patients (8%). There were 150 imported cases and 143 ICU
      acquired cases, of which 51% and 45%, respectively, were first identified through
      screening. Nasal swab cultures identified 84% of MRSA carriers. The incidence of
      all ICU-acquired cases and of acquired colonization or infection decreased from
      5.8% and 5.6% to 2.6% and 1.4% (P = .002 and P < .001), respectively, whereas
      that of imported cases remained unchanged (range, 3.8% to 4.3%; P = .8).
      Selective screening for nasal carriage during admission to high-risk areas may
      contribute to identification of a substantial proportion of cases of MRSA and to
      early implementation of effective control measures.

PMID- 9770156
TI  - Mycobacterium malmoense infections in the United States, January 1993 through
      June 1995.
AB  - Mycobacterium malmoense is a nontuberculous mycobacterium rarely encountered in
      the United States. However, isolations of M. malmoense from 73 patients (11 in
      1992, 35 in 1993, and 27 in 1994) were reported to the Centers for Disease
      Control and Prevention. We contacted state mycobacteriology laboratories and
      health care providers of patients whose M. malmoense isolations were reported
      from January 1993 through June 1995. To assign disease status for these patients,
      we used the criteria of the American Thoracic Society. Of 60 evaluable patients
      with disease status, only six (10%) had disease due to M. malmoense (five adults
      with pulmonary disease and one child with cervical lymphadenitis). We conclude
      that the number of patients with disease due to M. malmoense remains low.
      Increased isolation of this species may be due to the increased use of more
      sensitive and specific laboratory methods. For surveillance purposes, multiple M.
      malmoense isolates and age of younger than 10 years appear to be the best
      predictors for M. malmoense disease.

PMID- 9770157
TI  - Comparative study of mortality and morbidity in premature infants (birth weight,
      < 1,250 g) with candidemia or candidal meningitis.
AB  - Little information is available on long-term neurodevelopment of premature
      neonates with invasive candidal infections. We retrospectively studied the
      outcomes for 25 premature neonates (birth weight, < 1,250 g) with candidemia or
      candidal meningitis (cases) and compared them with 25 neonates matched for birth
      weight (+/- 100 g) and gestational age (+/- 1 week) (controls). Durations of
      antibiotic therapy, artificial ventilation, invasive catheterizations, and
      hyperalimentation were longer for cases than for controls. Cases had a higher
      final grade of intraventricular hemorrhage than did controls (median: 3.0 vs.
      2.5, respectively; P < .05). Forty-four percent (11 of 25) of cases and 16% (4 of
      25) of controls died (P > .05), and 29% (4 of 14) of surviving cases and 14% (3
      of 21) of controls were disabled (P > .05). More cases had combined mortality and
      neurodevelopmental disabilities than did controls (60% vs. 28%, respectively; P <
      .05). Use of invasive therapies should be minimized for premature neonates at
      risk for invasive candidal infection that is associated with adverse outcomes.

PMID- 9770158
TI  - Etiology of pneumonia and other common childhood infections requiring
      hospitalization and parenteral antimicrobial therapy. SE-TU Study Group.
AB  - The etiology of acute lower respiratory tract infections (mostly pneumonia) in
      children is well characterized, but these are only some of the community-acquired
      infections warranting parenteral antimicrobial therapy. We prospectively
      evaluated all such infections among children aged 3 months to 15 years by use of
      blood cultures, examination of nasopharyngeal aspirates, and serologies for 15
      viral, 7 bacterial, and 1 protozoal agent. Immunocompromised patients and those
      with urinary tract infection, meningitis, or osteoarticular infection were
      excluded. In all, 170 children were included. The pathogenic agent was identified
      in 62% of the cases. Bacteria were detected in 54%, and a pneumococcus was found
      in 59% of the cases identified. Viruses were found in 15% overall. Sole bacterial
      or viral infections were detected in 47.1% and 8.1%, respectively. Since thorough
      screening established the etiology in less than two-thirds of patients ill enough
      to be hospitalized and treated parenterally, better diagnostics are needed,
      especially to identify those who would truly benefit from antimicrobial therapy.

PMID- 9770159
TI  - Predictive value of cytomegalovirus (CMV) antigenemia and digene hybrid capture
      DNA assays for CMV disease in human immunodeficiency virus-infected patients.
AB  - Oral ganciclovir prophylaxis decreases the incidence of cytomegalovirus (CMV)
      disease among persons infected with the human immunodeficiency virus (HIV), but
      universal prophylaxis is not cost-effective. We evaluated urine and peripheral
      blood mononuclear cell cultures, a qualitative and quantitative antigenemia
      assay, and a commercially available CMV DNA hybridization assay for their ability
      to predict CMV disease in 138 HIV-infected patients. During a median follow-up of
      10 months, 23 patients (17%) developed CMV disease. The sensitivity, specificity,
      positive predictive value, negative predictive value, and mean lead times for the
      antigenemia assay (with use of a threshold of 8 positive cells per 10(5)
      peripheral blood mononuclear cells as a positive) were 74%, 91%, 63%, 95%, and 95
      days, respectively. Corresponding figures for the DNA hybridization assay were
      91%, 64%, 34%, 97%, and 152 days. These assays can identify patients at increased
      risk of CMV disease and should allow a strategy of preemptive therapy to be
      tested.

PMID- 9770160
TI  - Limulus amebocyte lysate assay for detection of endotoxin in patients with sepsis
      syndrome. AMCC Sepsis Project Working Group.
AB  - Clinical predictions alone are insufficiently accurate to identify patients with
      specific types of bloodstream infection; laboratory assays might improve such
      predictions. Therefore, we performed a prospective cohort study of 356 episodes
      of sepsis syndrome and did Limulus amebocyte lysate (LAL) assays for endotoxin.
      The main outcome measures were bacteremia and infection due to gram-negative
      organisms; other types of infection were secondary outcomes. Assays were defined
      as positive if the result was > or = 0.4 enzyme-linked immunosorbent assay units
      per milliliter. There were positive assays in 119 (33%) of 356 episodes. Assay
      positivity correlated with the presence of fungal bloodstream infection (P <
      .003) but correlated negatively with the presence of gram-negative organisms in
      the bloodstream (P = .04). A trend toward higher rates of mortality in the LAL
      assay-positive episodes was no longer present after adjusting for severity. Thus,
      results of LAL assay did not correlate with the presence of bacteremia due to
      gram-negative organisms or with mortality after adjusting for severity but did
      correlate with the presence of fungal bloodstream infection.

PMID- 9770161
TI  - Q fever during pregnancy: a public health problem in southern France.
AB  - We describe five cases of Q fever in pregnant women that were diagnosed during
      the last 3 years in the town of Martigues in Southern France. Analysis of our
      cases and the 18 other published cases shows that Q fever is a significant cause
      of morbidity and mortality in pregnancy. The disease may present as an acute or
      chronic infection and can be reactivated during subsequent pregnancies, as is
      seen with other mammals. In Martigues, Q fever is present in at least one per 540
      pregnancies and constitutes the most significant public health problem related to
      intrauterine infections.

PMID- 9770162
TI  - Predictors and outcome of admission for invasive Streptococcus pneumoniae
      infections at a Canadian children's hospital.
AB  - Rates of admission for invasive Streptococcus pneumoniae infection in children
      vary considerably between institutions. We performed a retrospective study to
      investigate factors used in the decision to admit patients with invasive S.
      pneumoniae infection to Alberta Children's Hospital. Of 254 patients who were
      initially assessed in the emergency department, 38.2% were admitted to the
      hospital. Significant risk factors for admission as determined by a logistic
      regression model included murmur (odds ratio [OR], 18.98; 95% confidence interval
      [CI], 4.08-88.23), focal infection (OR, 11.41; 95% CI, 5.07-25.67), and older age
      (OR, 2.72; 95% CI, 1.03-7.17). Higher hemoglobin level (OR, 0.96; 95% CI, 0.93
      0.99) and temperature of > 38.5 degrees C (OR, 0.39; 95% CI, 0.18-0.85) were
      associated with a lower risk of admission. Two patients died (case-fatality rate,
      0.7%). Despite the low rate of admission for invasive S. pneumoniae infections at
      our hospital, the mortality rate was comparable with those at institutions with
      higher rates of admission, thus suggesting that the factors we identified may be
      useful in deciding whether to admit patients with (or who are at high risk for)
      invasive S. pneumoniae infections.

PMID- 9770163
TI  - Lipid formulations of amphotericin B: clinical efficacy and toxicities.
AB  - Commercially available lipid formulations of amphotericin B (Abelcet, Amphotec,
      and AmBisome) represent a significant advance in drug delivery technology.
      Differences in biochemical, pharmacokinetic, and pharmacodynamic properties among
      the lipid products have been shown in in vitro and in vivo models. Clinical
      experience with these products has been primarily in patients either refractory
      to or intolerant of conventional amphotericin B deoxycholate (AmBd). None of the
      lipid-based products demonstrates superior efficacy when prospectively compared
      with AmBd in the treatment of documented infections. When used for the empirical
      treatment of febrile neutropenia, AmBisome significantly reduced the incidence of
      proven emergent fungal infections but did not improve short-term survival rates,
      in comparison with AmBd. Acute infusion-related adverse events vary, whereas
      nephrotoxicity is reduced with all three lipid formulations. Until superior
      efficacy is clearly shown (for documented infections) or pharmacoeconomic
      analyses document the value of these drugs, use of such expensive agents should
      be highly restricted to those who are intolerant of or refractory to AmBd.

PMID- 9770165
TI  - Germs, Dr. Billings, and the theory of focal infection.
AB  - Our understanding of infectious diseases continues to expand rapidly, and has led
      to the realization that microorganisms are responsible for, or at least
      contribute to, numerous diseases that were never before associated with
      infectious etiologies. However, a review of medical history reminds us that this
      is not so novel an idea. Not long after the widespread acceptance of bacteriology
      and the germ theory and with an increased awareness of public hygiene, there was
      a period during which it seemed that nearly all diseases would prove to be the
      result of infections. One popular proposal that championed such an idea was the
      theory of focal infection. This article reviews this theory by considering the
      key concepts and developments that likely inspired it, and examines the work of
      the theory's most visible proponent, Dr. Frank Billings.

PMID- 9770164
TI  - Intramedullary abscess of the spinal cord in the antibiotic era: clinical
      features, microbial etiologies, trends in pathogenesis, and outcomes.
AB  - We review the clinical features, microbial etiologies, mechanisms of infection,
      and outcomes of 25 cases of intramedullary abscess of the spinal cord (IASC)
      reported between 1977 and 1997, the modern era. All patients presented with motor
      and/or sensory neurological deficits. Back pain and/or radicular pain was common
      (60%); fever was present in a minority (40%) of patients. Preexisting
      abnormalities of the spinal cord and/or vertebral column were present in 44% of
      cases. Contiguous spread of infection through a congenital dermal sinus was the
      mechanism of infection in 24% of cases. The infection was fatal in 8% of cases;
      persistent neurological deficits were documented in 70% of patients who survived.
      To assess the impact of antimicrobial therapy on the pathogenesis and outcomes of
      IASC, cases reported in the modern era are compared with 42 cases of IASC
      reported between 1830 and 1944, the preantibiotic era.

PMID- 9770166
TI  - Comparison of peripheral and central biopsy sites for the isolation of Borrelia
      burgdorferi sensu lato from erythema migrans skin lesions.
AB  - To compare peripheral and central biopsy sites for the isolation of Borrelia
      burgdorferi sensu lato from typical erythema migrans lesions, two biopsy
      specimens (one from the margin and the other from the center of the lesion) were
      taken from each of 53 adult patients. Thirty-four (32.1%) of the 106 biopsy
      specimens and 23 (43.4%) of the 53 patients were culture-positive. Spirochetes
      were isolated in 19 (35.9%) of the 53 central and 15 (28.3%) of the 53 peripheral
      biopsies (nonsignificant difference). In 8 cases only the central specimen, in 4
      cases only the peripheral specimen, and in 11 cases both specimens were positive.
      In a comparison of 36 annular and 17 homogeneous lesions, borreliae were isolated
      from 15 (41.7%) of the former and 8 (47.1%) of the latter. In the annular-lesion
      biopsies, 11 central and 12 peripheral specimens were culture-positive. In the
      homogeneous-lesion biopsies, eight central and three peripheral specimens were
      culture-positive (nonsignificant difference); there were no culture-positive
      results solely for the margin of homogeneous lesions. This study demonstrates
      that B. burgdorferi sensu lato may be isolated from the central aspect of
      erythema migrans lesions as efficiently as from the peripheral aspect.

PMID- 9770167
TI  - Mycobacterium bovis osteomyelitis involving a hip arthroplasty after
      intravesicular bacille Calmette-Guerin for bladder cancer.
AB  - Bacille Calmette-Guerin (BCG), an attenuated strain of Mycobacterium bovis, is
      one of the most effective agents in the treatment of superficial bladder cancer.
      BCG osteomyelitis is an infrequent complication of intravesicular BCG therapy;
      only five cases of BCG vertebral osteomyelitis have been reported in the
      literature. Similarly, the infection of an indwelling extravascular device by BCG
      is rare; there is only one previous report documenting infection associated with
      an automated implantable cardiac defibrillator. We report a case of BCG
      osteomyelitis involving a hip arthroplasty that occurred after intravesicular
      administration of BCG for bladder cancer, and we review the risk factors
      predisposing to such infections and their treatment.

PMID- 9770168
TI  - Primary cutaneous aspergillosis in human immunodeficiency virus-infected
      patients: two cases and review.

PMID- 9770169
TI  - Itraconazole therapy for primary cutaneous aspergillosis in patients with AIDS.

PMID- 9770170
TI  - Norwegian scabies and a toxic shock syndrome toxin 1-producing strain of
      Staphylococcus aureus endocarditis in a patient with trisomy 21.

PMID- 9770171
TI  - Of mites and men--lessons in scabies for the infectious diseases clinician.

PMID- 9770172
TI  - Bloody diarrhea caused by Klebsiella pneumoniae: a new mechanism of bacterial
      virulence?

PMID- 9770173
TI  - Mycobacterium heidelbergense species nov. infection mimicking a lung tumor.

PMID- 9770175
TI  - Hepatitis A in human immunodeficiency virus-infected patients.

PMID- 9770174
TI  - Immune thrombocytopenia caused by piperacillin/tazobactam.

PMID- 9770176
TI  - Successful treatment of human herpesvirus 6 encephalitis in a bone marrow
      transplant recipient.

PMID- 9770177
TI  - Isolation of type B influenza virus from the blood of children.

PMID- 9770178
TI  - Declining prevalence of cryptosporidiosis in San Francisco.

PMID- 9770179
TI  - Bloody diarrhea caused by Plesiomonas shigelloides proctitis in a human
      immunodeficiency virus-infected patient.

PMID- 9770180
TI  - Clarithromycin therapy for bacillary peliosis did not prevent bacillary
      angiomatosis.

PMID- 9770181
TI  - Fatal cytomegalovirus infection in a patient without evidence of prior
      immunodeficiency.

PMID- 9770182
TI  - Isolated thrombocytopenic purpura associated with infection due to verocytotoxin
      (Shiga toxin)-producing Escherichia coli serotype O26:H11.

PMID- 9770185
TI  - Neuropeptides, the hypothalamus and obesity: insights into the central control of
      body weight.
AB  - Body weight tends to remain relatively stable for long periods over an adult's
      lifespan. Dieting can reduce weight by 5-10%, but in most individuals attempts to
      lose larger amounts of weight are counteracted by a reduction in energy
      expenditure and an increase in hunger. The fact that body weight appears to be
      actively defended in this manner suggests that it is homeostatically regulated at
      a certain "set-point". Such a mechanism is likely to be centrally controlled by
      the brain since the hypothalamus can sense the amount of adipose tissue stored in
      the body and can alter both energy intake and expenditure. Over the past four
      years a number of major advances have reinforced the critical role the brain may
      play in controlling body weight, and these have greatly enhanced our
      understanding of this area. Advances have included the identification of several
      genetic mutations that cause obesity in animal models, examination of the
      metabolic consequences of such mutations and the development of mice with
      genetically engineered altered neuropeptide levels. This review summarises what
      has been recently discovered about the regulation of body weight by the brain and
      how this may be disrupted in obesity.

PMID- 9770183
TI  - Multiple painful indurated erythematous nodular skin lesions associated with
      Pseudomonas aeruginosa septicemia.

PMID- 9770184
TI  - Gastrointestinal basidiobolomycosis.

PMID- 9770186
TI  - Primary intraosseous malignant peripheral nerve sheath tumor: a case report and
      review of the literature.
AB  - Primary intraosseous malignant peripheral nerve sheath tumors (MPNST) are
      exceptionally rare; the case reported here represents the first documented
      example occurring in the spinal column. The tumor arose in the second cervical
      vertebra of a forty year old woman of Asian origin. She had no stigmata of von
      Recklinghausen's disease (VRD). Plain radiographs and magnetic resonance imaging
      showed an osteolytic lesion within the expanded body of the vertebra. Histology
      revealed spindle-shaped tumor cells with nuclei showing pleomorphism, pallisading
      and mitotic activity. The cells stained positively for S-100 protein. The patient
      underwent stabilisation of the cervical spine and tumor excision as a two-stage
      procedure. She died of pulmonary metastases one year later. We have reviewed the
      literature on the pathology of these tumors.

PMID- 9770188
TI  - Broadsheet number 45: thin core biopsy of prostate. The Royal College of
      Pathologists of Australia.

PMID- 9770187
TI  - Multifocal micronodular pneumocyte hyperplasia, lymphangiomyomatosis and clear
      cell micronodules of the lung in a Chinese female patient with tuberous
      sclerosis.
AB  - Tuberous sclerosis is a rare genetic disease with protean clinical
      manifestations. The lesion most commonly described in the lung is
      lymphangiomyomatosis. There have been recent reports of multifocal micronodular
      pneumocyte hyperplasia, as well as a single case documentation of a clear cell
      tumor of the lung, in patients affected by the disease. We detail a case of a
      female Chinese patient with tuberous sclerosis who was incidentally discovered to
      have bilateral pneumothoraces. The open lung biopsy revealed combined
      histological features of multifocal micronodular pneumocyte hyperplasia,
      lymphangiomyomatosis and clear cell micronodules.

PMID- 9770189
TI  - Test and Teach. Number Ninety: Part 1. Plexiform fibrohistiocytic tumor.

PMID- 9770190
TI  - Beta-carotene reduces the ductular (oval) cell reaction in the liver of Wistar
      rats submitted to the resistant hepatocyte model of carcinogenesis.
AB  - The morphology of livers of Wistar rats treated with beta-carotene (BC), vitamin
      A (VA, retinol acetate) or corn oil (CO, controls) and submitted to the resistant
      hepatocyte model of carcinogenesis was studied. Preneoplastic lesions (PNL) were
      smaller and less numerous in the BC group. The latter group also presented fewer
      placental glutathione-S-transferase (GST-P) positive and hematoxylin and eosin
      (H&E) distinguishable PNL, with smaller mean areas and smaller mean areas of the
      liver occupied by PNL. Clear cell foci predominated in BC livers. In picrosirius
      stained liver sections, fibrosis, whether or not accompanying the bile ductular
      cells, surrounded only 16.67% of PNL in the BC group, as compared to 35.71% in
      the VA group and 87.72% in the CO group. Moreover, the ductular cell reaction was
      smaller in the BC group. Smooth muscle actin-positive cells surrounded some PNL,
      mostly in CO rats, and less frequently in the VA and BC groups. Examination by
      transmission electron microscopy (TEM) showed that cells with nuclei similar to
      those of perisinusoidal cells, devoid of cytoplasmic fat globules, probably
      represented myofibroblasts derived from Ito cells and accompanied the ductular
      cell reaction. On the basis of these results, we suggest that BC reduced not only
      the PNL but also the ductular (oval) cell reaction in this experimental model.

PMID- 9770191
TI  - Cautionary note on the use of end-labelling DNA fragments for detection of
      apoptosis.
AB  - The gastrointestinal epithelum undergoes a continual process of cell renewal
      which is partly regulated by apoptosis. The process of growth and differentiation
      is greatly enhanced in the terminal ileum after massive small bowel resection, a
      well-established model of intestinal adaptation. We have applied the terminal
      deoxynucleotidyl transferase (TdT)-mediated UTP nick end-labelling (TUNEL) method
      to establish the role of apoptosis in intestinal adaption in terminal ileum of
      control animals after small bowel resection. Healing skin wound and lymph node
      were used as positive control tissue for apoptotic cells. We report that
      considerable inter-animal variation was observed in the intestinal tissue. We
      believe that caution is required in the interpretation of TUNEL staining in
      intestinal tissue and in its use as a specific marker for apoptosis in this
      setting.

PMID- 9770192
TI  - p53 protein immunoreactivity in fibrohistiocytic tumors of the skin.
AB  - Abnormal expression of the 53 kDa nuclear phosphoprotein produced by the p53 gene
      is observed in many human cancers. p53 nuclear immunoreactivity is found commonly
      in tumor cells. Immunohistochemistry was performed using a monoclonal antibody,
      DO-7 (DAKO, Denmark; cat. no. M7001; 1:100 dilution), to investigate p53 protein
      immunoreactivity in a group of cutaneous fibrohistiocytic tumors that are known
      to be locally aggressive. The study group consisted of dermatofibrosarcoma
      protuberans (DFSP) (n = 14) and atypical fibroxanthoma (AFX) (n = 7). Cases of
      dermatofibroma (DF) (n = 16) formed the benign control group. Intense nuclear
      immunostaining for p53 protein was observed in 71% of DFSP and 86% of AFX. None
      of the dermatofibromas showed strong p53 nuclear immunostaining. Statistical
      analyses revealed significant differences in p53 immunoreactivity between DFSP
      and DF (P = 0.0001, chi 2 test) and between AFX and DF (P = 0.0001, chi 2 test).
      In conclusion, increased p53 protein immunoreactivity is found in DFSP and AFX
      but not in DF. These differences in p53 immunoreactivity suggest that increased
      expression of the protein may be important in the pathogenesis of the more
      aggressive group of fibrohistiocytic tumors.

PMID- 9770193
TI  - Guidelines for the collection, processing, storage and of administration of
      hemopoietic stem and progenitor cells for transplantation. Report of the Working
      Party on Hemopoietic Stem Cell Processing, Hematology Discipline Advisory
      Committee, the Royal College of Pathologists of Australasia.

PMID- 9770194
TI  - Identification of Australian arboviruses in inoculated cell cultures using
      monoclonal antibodies in ELISA.
AB  - An ELISA using a panel of specific monoclonal antibodies was developed to
      identify all alpha and flaviviruses isolated from mosquitoes caught throughout
      Australia. This technique is sensitive and rapid and is more specific than the
      traditional methods used to identify flaviviruses. The ability to identify
      unknown virus isolates from field-caught mosquitoes quickly and accurately
      improves the efficiency of arbovirus surveillance programs and allows health
      authorities to give an early warning of an increased health risk from a mosquito
      borne virus in a particular region.

PMID- 9770195
TI  - Monitoring of serum aminoglycoside levels with once-daily dosing.
AB  - There is considerable confusion as to how to monitor serum aminoglycoside levels
      when using once-daily dosing. At least five methods are in use in Australia. We
      prospectively assessed 100 consecutive once-daily courses of gentamicin or
      tobramycin, during which 120 pre-dose and 213 sets of immediate post-dose and six
      hour post-dose levels were taken. By using the six hour post-dose level we were
      able to compare dosage recommendations made using methods known as ALADDIN,
      DOSECALC and the Australian Antibiotic Guidelines nomogram (AAGN). There were
      statistically significant differences in the doses recommended by each method.
      When comparing each of the three methods, at least 25% of dosage recommendations
      differed by more than 80 mg per dose. Although we have not been able to determine
      the clinical significance of these differences, we are concerned that methods
      used in dosage adjustment of aminoglycosides differ so widely in their
      recommendations. Presumably the ALADDIN method, which utilises two post-dose
      levels to determine an area under aminoglycoside concentration-time curve, gives
      more accurate pharmacokinetic information than methods which rely on a single
      level. Comparative cost-effectiveness studies of different methods, although in
      practice difficult to perform, should be undertaken to resolve the optimal
      management of patients receiving aminoglycosides once-daily.

PMID- 9770196
TI  - Chlamydia pneumoniae DNA is not detectable within sarcoidosis tissue.
AB  - Sarcoidosis is a granulomatous disease of unknown etiology. Recent studies have
      suggested the possibility of a bacterial origin with Chlamydia pneumoniae being
      one of the many bacteria considered. The aim of this study was to use the
      polymerase chain reaction (PCR) in an attempt to identify C. pneumoniae within
      fresh/frozen sarcoidosis tissue. Tissue from 20 sarcoidosis patients and 17
      controls was evaluated. DNA was extracted from all tissue specimens and PCR
      amplified with primers specific for C. pneumoniae. All study tissues were
      negative for the presence of DNA sequences from C. pneumoniae. These findings
      could not be attributed to PCR inhibition or to lack of sensitivity of the PCR
      assay. The negative finding suggests either that there is no involvement between
      C. pneumoniae and sarcoidosis or that, having incited granulomata formation, it
      is no longer present in detectable amounts.

PMID- 9770197
TI  - Heterogeneous expression of fusidic acid resistance in Staphylococcus aureus with
      plasmid or chromosomally encoded fusidic acid resistance genes.
AB  - Fusidic acid resistance expression in a methicillin susceptible Staphylococcus
      aureus strain (WBG1576), which carries fusidic acid resistance on plasmid pUB101,
      and a prevalent Western Australian methicillin-fusidic acid resistant strain
      (WBG8287) were compared. WBG8287 carries fusidic acid resistance on the
      chromosome and its plasmid content has no effect on the levels of this
      resistance. WBG1576 and WBG8287 exhibited similar heterogeneous populations in
      respect to fusidic acid resistance levels in population analyses. A high-level
      fusidic acid resistant mutant of WBG1576 (BE8) had alterations in Smal
      chromosomal profiles, but not in plasmid size or resistance expression. Mutations
      causing increased fusidic acid resistance in WBG1576 are chromosomally located. A
      high-level fusidic acid resistant mutant of WBG8287 (BE3) had no alterations in
      Smal chromosomal profiles, or plasmid content and resistances. Comparison of
      resistance levels to kanamycin and spectinomycin, between high-level resistant
      colonies of WBG8287 and WBG8287, indicate that mutations in the chromosomal gene
      fusA, which encodes elongation factor-G, are probably the cause of the increased
      resistance levels observed in these mutant strains.

PMID- 9770198
TI  - Capillary electrophoresis: new technology for DNA diagnostics.
AB  - New innovations in the diagnostic laboratory achieve their full potential when
      they can be automated. Increasingly molecular biology (DNA) techniques are being
      utilised in traditional pathology disciplines, as well as the more recent ones of
      cytogenetics and molecular genetics. Molecular biology was first exploited for
      diagnostic purposes when Southern blotting became established. However the time
      consuming nature of the methodology, as well as the skills required, made it
      difficult for Southern blotting to be used routinely in the service laboratory.
      Subsequently the invention of PCR facilitated the approach to DNA diagnostics.
      Today PCR in commercial or home-made kits is used for a range of procedures. The
      steps required to amplify DNA with PCR can also be fully automated. However the
      analysis of PCR products, which frequently requires slab gel electrophoresis and
      toxic chemicals or radioisotopes for visualisation, remains difficult to
      automate. An alternative way for analysing PCR products is now available through
      capillary electrophoresis. With this technique, automation can be extended to
      sample loading, electrophoresis and data analysis. The use of toxic chemicals or
      radioisotopes can be avoided.

PMID- 9770201
TI  - Cryptococcal myositis: a case report and review of the literature.
AB  - Only rare cases of cryptococcal myositis have been previously reported in the
      literature. All of these cases have occurred in the setting of human
      immunodeficiency virus (HIV) infection. We report a case of cryptococcal myositis
      diagnosed premortem on a needle biopsy in a heart transplant patient undergoing
      immunosuppressive therapy.

PMID- 9770199
TI  - The role of peer review in internal quality assurance in cytopathology.
AB  - In 1992 we set up a peer review system to address all the steps involved in the
      production of a cytopathology report. The aim of the study was to generate
      accurate, timely and clinically relevant cytopathology reports. During a four
      year period we monitored and recorded activities such as turnaround time and
      adequacy of sampling as well as errors including typographical, SNOMED, coding,
      technical, labelling of slides, clerical, macroscopic and microscopic errors. The
      findings were discussed at weekly laboratory meetings attended by technical,
      scientific, clerical and medical staff. Minor errors not needing immediate action
      were discussed and incorporated as future improvements into the workings of the
      laboratory. For major discrepancies with potential implications for patient
      management, supplementary reports were issued and the relevant clinician was
      informed of the outcome. Detailed peer review of 1.3% of the total workload,
      during the period of the study, led to comments on some aspects of the original
      report in 24.9% of the reviewed cases. The majority of comments (57%) were minor,
      concerning issues related to the pre-analytical (clinical history, demographics,
      clerical and technical) aspects of the cases. The post analytical (microscopic
      description, diagnosis, recommendation and coding) phase of cases attracted 43%
      of the comments. In 1.1% of cases, the reviewer made suggestions regarding the
      diagnosis, and in 0.4% of cases a different recommendation was made. Cost-benefit
      analysis revealed that our internal quality assurance (IQA) activities added
      $1.20 to the total cost of each cytopathology case received and processed in the
      laboratory. On the benefit side, analysis of the data showed a continuous fall in
      the number of errors in both the pre-analytical and post-analytical phases of
      report generation. Furthermore, the turnaround time fell from 3.0 days at the
      beginning of the study to 1.7 days at present. These IQA activities have
      highlighted the importance of such a review system in detecting errors in
      cytopathology reporting. Recognition of the fact that cytopathology suffers from
      observer variability has led to the adoption of a uniform approach to cytological
      reporting among cytotechnologists and pathologists.

PMID- 9770202
TI  - Non-malignant bone marrow necrosis: a report of two cases.
AB  - We present two cases of bone marrow necrosis not associated with malignancy,
      infection or sickle cell disease. The first case, a 28 year old woman with the
      antiphospholipid syndrome and a factor V Leiden abnormality, suffered an illness
      characterised by multiple organ thromboses, anemia and refractory
      thrombocytopenia. She had documented bone marrow necrosis of the posterior iliac
      spine and numerous hot spots on bone scanning suggestive of widespread marrow
      necrosis. This patient also suffered hepatic infarcts and a miscarriage and may
      represent an explanation for the previously described "catastrophic
      antiphospholipid syndrome". The second patient developed widespread bone pain
      over a three week period, underwent a cholecystectomy and suffered major post
      operative complications including a delayed transfusion reaction and disseminated
      intravascular coagulation. Pancytopenia developed and bone marrow trephines from
      numerous foci revealed widespread bone marrow necrosis. The only predisposing
      factor to account for this presentation was that the patient had been sniffing
      glue for two months prior to the illness, as the foci of necrosis had healed on
      repeat marrow examination eight weeks later when the patient had abstained from
      glue sniffing. This case may represent a reversible, toxic cause of bone marrow
      necrosis.

PMID- 9770204
TI  - Primary hepatic osteosarcoma: case report and literature review.
AB  - We describe a primary osteosarcoma of the liver in a 72 year old man. The man was
      symptomatic and had suffered abdominal pain and distension for four months before
      he died. At autopsy a large tumor of the liver with direct extension into
      adjacent structures was found. There was no evidence of primary tumor or primary
      bone lesion at any other site. Histologically, the tumor comprised malignant
      cells producing abundant osteoid arranged in a lace-like pattern. Smaller
      chondroblastic and fibroblastic components were also present. These findings were
      in keeping with a diagnosis of primary hepatic osteosarcoma.

PMID- 9770203
TI  - Localised primary amyloidosis of inguinal lymph node with superimposed bone
      metaplasia.
AB  - We present here a case of localised primary amyloidosis of the right inguinal
      lymph node in a 42 year old female. On gross examination the specimen was 4.0 x
      4.0 x 3.2 cm in size with a tan-pink color and two whitish-yellow areas of hard
      consistency. Histologically the lymph node was replaced by an eosinophilic
      amorphous material, alkaline Congo red, crystal violet, thioflavine T and sodium
      sulphate-alcian blue (SAB). We observed areas of mature bone metaplasia
      alternating with sheets of plasma cells and clusters of foreign body giant cell
      reaction. Immunohistochemical study showed anti-lambda chain staining within the
      amorphous material. The negative clinical history, physical examination, normal
      serum electrophoresis and bone marrow and rectal biopsy allowed us to make the
      diagnosis of localised primary amyloidosis of lymph node. The patient is alive
      and without evidence of disease progression to systemic amyloidosis or plasma
      cell dyscrasia, after clinical follow-up of seven years.

PMID- 9770205
TI  - Pathology, pathologists and problem-based learning.

PMID- 9770206
TI  - Neuropathological biopsy diagnoses in clinical practice: how thorough and
      reproducible are they?

PMID- 9770207
TI  - Pharmacophore and pseudoreceptor modelling of class Ib antiarrhythmic and local
      anaesthetic lidocaine analogues.
AB  - A molecular modelling study was carried out in order to investigate the molecular
      binding behaviour of antiarrhythmically and local anaesthetically active
      aminoacylanilide derivatives from the lidocaine type at their specific sodium
      channel binding site. An examination of relevant X-ray structures and of results
      derived from systematic and random search conformational analyses yielded
      information about the spatial requirements of these sodium channel blocking
      compounds. Common structural elements in combination with their non-covalent
      interaction potentials were used to generate a rational pharmacophore model. To
      further support and refine this model an atomistic pseudoreceptor of the Na+
      channel binding site was constructed using a training set of eight well-defined
      lidocaine homologues. With the final pseudoreceptor, composed of tyrosine,
      phenylalanine, serine, valine and three isoleucine residues, it was possible to
      correlate experimental versus calculated dissociation constants of the training
      set with a correlation coefficient of 0.98. To test the accuracy of this model,
      the affinities of three additional compounds, not used for pseudoreceptor
      modelling, were predicted. After free relaxation within the binding cavity using
      a Monte-Carlo minimization the test set yielded a RMS error in the prediction of
      0.039 kcal/mol corresponding to an uncertainty factor of 1.06. In addition, this
      hypothetical receptor model provides evidence for an exceptional binding mode of
      the lidocaine metabolite glycinexylidide (GX) which could explain its low binding
      affinity and thereby possibly the minor physiological effects with respect to
      lidocaine.

PMID- 9770208
TI  - Synthesis and anticonvulsant activity of some 2-N-(phthalimido)-1-alkyl esters.
AB  - Synthesis and physicochemical properties of new 2-N-(phthalimido)-1-alkyl esters
      are described. Esters were synthesized from aromatic and heterocyclic acids with
      appropriate bromoalkyl phthalimides in the presence of 1,8-diazabicyclo[5,4,0]
      undec-7-ene or triethylamine. The obtained compounds were evaluated for
      anticonvulsant activity. The display protection against MES and ScMet-induced
      seizures.

PMID- 9770209
TI  - Antitumor activity of new derivatives of 1,3-diazaheterocycles.
AB  - 2-Naphthylidene derivatives of 1,3-diazaheterocycles were prepared in order to
      investigate the relationship between their structure and anticancer activity.
      Preliminary screening in the standard in vitro assay using 60-tumor cell lines
      showed that some of these derivatives exhibited a moderate growth inhibition
      activity on various tumor subpanel cell lines between 10(-6)-10(-4) molar
      concentration. The results obtained show that the structural features are
      important in inhibiting tumor cell lines.

PMID- 9770210
TI  - [Cleavage and biotransformation of the central muscle relaxant chlormezanone].
AB  - Chlormezanone, a chiral centrally acting muscle relaxant, will be cleaved at its
      S-C-1 bond by an autoprotolytic process. The optimum of chemical stability exists
      between pH 2 up to pH 9 with a maximum at pH 7.4. The plasma half life at 37
      degrees C is 76 h. Enzymes do attack the products of cleavage namely 4
      chlorobenzaldehyde and 2-carboxyethane-sulfinic-acid-N-methyl-amide. The main
      metabolite in urine is 4-chlorohippuric acid in the range of up to 70% of the
      oral administered dose to humans. No cytochrome P-450 is engaged in the cleavage
      of the S-C-bond.

PMID- 9770211
TI  - Stimulation of endothelial angiotensin-converting enzyme by morphine via non
      opioid receptor mediated processes.
AB  - In this study, we examined the influence of morphine and naloxone on the
      enzymatic activity of different ecto-peptidases located on the surface of
      endothelial cells. Morphine increased in a concentration dependent manner the
      degradation of Leu-enkephalin in cultivated bovine aortic endothelial cells.
      Naloxone, a morphine antagonist, did not prevent this effect, but caused it as
      well. The enhanced Leu-enkephalin degradation was due to an increase in the
      activity of angiotensin-converting enzyme (ACE), whereas the activity of other
      ecto-peptidases (aminopeptidase N and neutral endopeptidase) was not influenced.
      Despite a high non-specific binding of [3H]-morphine, no specific opioid receptor
      binding on the endothelial cells could be detected. Autoradiographic
      investigations with native, cryostat-sectioned cells demonstrated that [3H]
      morphine was nearly exclusively located within the nuclei. The present results
      suggests that the morphine effect concerning ACE activity is not mediated via
      opioid receptors but presumably by interactions within the cell nucleus.

PMID- 9770212
TI  - The effect of chard (Beta vulgaris L. var. cicla) on the skin of streptozotocin
      induced diabetic rats.
AB  - Chard (Beta vulgaris L. var. cicla) is one of the plants used as hypoglycaemic
      agent by diabetics in Turkey and it has been reported to reduce blood glucose.
      The purpose of this study was to investigate the effect of feeding chard on
      diabetes induced impairments in rat skins. Uncontrolled induced diabetes caused
      significant increases in nonenzymatic glycosylation of skin proteins, lipid
      peroxidation and blood glucose. Administration of chard extract inhibited these
      effects except the increase in lipid peroxidation. SDS-polyacrylamide gel
      electrophoresis revealed no significant differences in any protein bands between
      any of the groups. The data indicate that the use of chard may be effective in
      preventing or at least retarding the development of some diabetic complications.

PMID- 9770213
TI  - A pyranocoumarin and two alkaloids (one with antispasmodic effect) from Citrus
      deliciosa.
AB  - One pyranocoumarin (xanthyletin, 1) and two acridone alkaloids (2',2'-dimethyl
      (pyrano5',6':3:4)-1,5-dihydroxy, 6-methoxy, 10-methylacridone, 3, and citpressine
      I, 4), were isolated from the roots of Citrus deliciosa Ten (Rutacea). Their
      structures were elucidated by spectroscopic methods. Reported 13C NMR assignments
      of alkaloid 3 have been corrected and those of alkaloid 4 are reported for the
      first time Alkaloid 3 was found to have antispasmodic effect on isolated ileum
      segments excised from male rabbits.

PMID- 9770214
TI  - Synthesis and chemotherapeutic activity of a carbocyclic analogue of tegafur.

PMID- 9770215
TI  - Study of bacampicillin hydrochloride durability in tablets.

PMID- 9770217
TI  - Euglena gracilis: inhibition of chloroplast mutagenesis by some commercial
      salicylates.

PMID- 9770216
TI  - Plasma protein binding of the local anaesthetic drug articaine and its metabolite
      articainic acid.

PMID- 9770218
TI  - Insulin from Rapana venosa (Valenciennes 1846).

PMID- 9770219
TI  - Visual attention mediated by biased competition in extrastriate visual cortex.
AB  - According to conventional neurobiological accounts of visual attention, attention
      serves to enhance extrastriate neuronal responses to a stimulus at one spatial
      location in the visual field. However, recent results from recordings in
      extrastriate cortex of monkeys suggest that any enhancing effect of attention is
      best understood in the context of competitive interactions among neurons
      representing all of the stimuli present in the visual field. These interactions
      can be biased in favour of behaviourally relevant stimuli as a result of many
      different processes, both spatial and non-spatial, and both bottom-up and top
      down. The resolution of this competition results in the suppression of the
      neuronal representations of behaviourally irrelevant stimuli in extrastriate
      cortex. A main source of top-down influence may derive from neuronal systems
      underlying working memory.

PMID- 9770221
TI  - A computational theory of visual attention.
AB  - A computational theory of visual attention is presented. The basic theory (TVA)
      combines the biased-choice model for single-stimulus recognition with the fixed
      capacity independent race model (FIRM) for selection from multi-element displays.
      TVA organizes a large body of experimental findings on performance in visual
      recognition and attention tasks. A recent development (CTVA) combines TVA with a
      theory of perceptual grouping by proximity. CTVA explains effects of perceptual
      grouping and spatial distance between items in multi-element displays. A new
      account of spatial focusing is proposed in this paper. The account provides a
      framework for understanding visual search as an interplay between serial and
      parallel processes.

PMID- 9770220
TI  - Sensory gain control (amplification) as a mechanism of selective attention:
      electrophysiological and neuroimaging evidence.
AB  - Both physiological and behavioral studies have suggested that stimulus-driven
      neural activity in the sensory pathways can be modulated in amplitude during
      selective attention. Recordings of event-related brain potentials indicate that
      such sensory gain control or amplification processes play an important role in
      visual-spatial attention. Combined event-related brain potential and neuroimaging
      experiments provide strong evidence that attentional gain control operates at an
      early stage of visual processing in extrastriate cortical areas. These data
      support early selection theories of attention and provide a basis for
      distinguishing between separate mechanisms of attentional suppression (of
      unattended inputs) and attentional facilitation (of attended inputs).

PMID- 9770222
TI  - How do we select perceptions and actions? Human brain imaging studies.
AB  - The selective nature of human perception and action implies a modulatory
      interaction between sensorimotor processes and attentional processes. This paper
      explores the use of functional imaging in humans to explore the mechanisms of
      perceptual selection and the fate of irrelevant stimuli that are not selected.
      Experiments with positron emission tomography show that two qualitatively
      different patterns of modulation of cerebral blood flow can be observed in
      experiments where non-spatial visual attention and auditory attention are
      manipulated. These patterns of modulation of cerebral blood flow modulation can
      be described as gain control and bias signal mechanisms. In visual and auditory
      cortex, the dominant change in cerebral blood flow associated with attention to
      either modality is related to a bias signal. The relation of these patterns of
      modulation to attentional effects that have been observed in single neurons is
      discussed. The existence of mechanisms for selective perception raises the more
      general question of whether irrelevant ignored stimuli are nevertheless
      perceived. Lavie's theory of attention proposes that the degree to which ignored
      stimuli are processed varies depending on the perceptual load of the current
      task. Evidence from behavioural and functional magnetic resonance imaging studies
      of ignored visual motion processing is presented in support of this proposal.

PMID- 9770223
TI  - Feature binding, attention and object perception.
AB  - The seemingly effortless ability to perceive meaningful objects in an integrated
      scene actually depends on complex visual processes. The 'binding problem'
      concerns the way in which we select and integrate the separate features of
      objects in the correct combinations. Experiments suggest that attention plays a
      central role in solving this problem. Some neurological patients show a dramatic
      breakdown in the ability to see several objects; their deficits suggest a role
      for the parietal cortex in the binding process. However, indirect measures of
      priming and interference suggest that more information may be implicitly
      available than we can consciously access.

PMID- 9770224
TI  - Converging levels of analysis in the cognitive neuroscience of visual attention.
AB  - Experiments using behavioural, lesion, functional imaging and single neuron
      methods are considered in the context of a neuropsychological model of visual
      attention. According to this model, inputs compete for representation in multiple
      visually responsive brain systems, sensory and motor, cortical and subcortical.
      Competition is biased by advance priming of neurons responsive to current
      behavioural targets. Across systems competition is integrated such that the same,
      selected object tends to become dominant throughout. The behavioural studies
      reviewed concern divided attention within and between modalities. They implicate
      within-modality competition as one main restriction on concurrent stimulus
      identification. In contrast to the conventional association of lateral
      attentional focus with parietal lobe function, the lesion studies show
      attentional bias to be a widespread consequence of unilateral cortical damage.
      Although the clinical syndrome of unilateral neglect may indeed be associated
      with parietal lesions, this probably reflects an assortment of further deficits
      accompanying a simple attentional imbalance. The functional imaging studies show
      joint involvement of lateral prefrontal and occipital cortex in lateral
      attentional focus and competition. The single unit studies suggest how
      competition in several regions of extrastriate cortex is biased by advance
      priming of neurons responsive to current behavioural targets. Together, the
      concepts of competition, priming and integration allow a unified theoretical
      approach to findings from behavioural to single neuron levels.

PMID- 9770225
TI  - Cross-modal links in spatial attention.
AB  - A great deal is now known about the effects of spatial attention within
      individual sensory modalities, especially for vision and audition. However, there
      has been little previous study of possible cross-modal links in attention. Here,
      we review recent findings from our own experiments on this topic, which reveal
      extensive spatial links between the modalities. An irrelevant but salient event
      presented within touch, audition, or vision, can attract covert spatial attention
      in the other modalities (with the one exception that visual events do not attract
      auditory attention when saccades are prevented). By shifting receptors in one
      modality relative to another, the spatial coordinates of these cross-modal
      interactions can be examined. For instance, when a hand is placed in a new
      position, stimulation of it now draws visual attention to a correspondingly
      different location, although some aspects of attention do not spatially remap in
      this way. Cross-modal links are also evident in voluntary shifts of attention.
      When a person strongly expects a target in one modality (e.g. audition) to appear
      in a particular location, their judgements improve at that location not only for
      the expected modality but also for other modalities (e.g. vision), even if events
      in the latter modality are somewhat more likely elsewhere. Finally, some of our
      experiments suggest that information from different sensory modalities may be
      integrated preattentively, to produce the multimodal internal spatial
      representations in which attention can be directed. Such preattentive cross-modal
      integration can, in some cases, produce helpful illusions that increase the
      efficiency of selective attention in complex scenes.

PMID- 9770226
TI  - Place cells, navigational accuracy, and the human hippocampus.
AB  - The hippocampal formation in both rats and humans is involved in spatial
      navigation. In the rat, cells coding for places, directions, and speed of
      movement have been recorded from the hippocampus proper and/or the neighbouring
      subicular complex. Place fields of a group of the hippocampal pyramidal cells
      cover the surface of an environment but do not appear to do so in any systematic
      fashion. That is, there is no topographical relation between the anatomical
      location of the cells within the hippocampus and the place fields of these cells
      in an environment. Recent work shows that place cells are responding to the
      summation of two or more Gaussian curves, each of which is fixed at a given
      distance to two or more walls in the environment. The walls themselves are
      probably identified by their allocentric direction relative to the rat and this
      information may be provided by the head direction cells. The right human
      hippocampus retains its role in spatial mapping as demonstrated by its activation
      during accurate navigation in imagined and virtual reality environments. In
      addition, it may have taken on wider memory functions, perhaps by the
      incorporation of a linear time tag which allows for the storage of the times of
      visits to particular locations. This extended system would serve as the basis for
      a spatio-temporal event or episodic memory system.

PMID- 9770227
TI  - Neural representation of objects in space: a dual coding account.
AB  - I present evidence on the nature of object coding in the brain and discuss the
      implications of this coding for models of visual selective attention.
      Neuropsychological studies of task-based constraints on: (i) visual neglect; and
      (ii) reading and counting, reveal the existence of parallel forms of spatial
      representation for objects: within-object representations, where elements are
      coded as parts of objects, and between-object representations, where elements are
      coded as independent objects. Aside from these spatial codes for objects,
      however, the coding of visual space is limited. We are extremely poor at
      remembering small spatial displacements across eye movements, indicating (at
      best) impoverished coding of spatial position per se. Also, effects of element
      separation on spatial extinction can be eliminated by filling the space with an
      occluding object, indicating that spatial effects on visual selection are
      moderated by object coding. Overall, there are separate limits on visual
      processing reflecting: (i) the competition to code parts within objects; (ii) the
      small number of independent objects that can be coded in parallel; and (iii) task
      based selection of whether within- or between-object codes determine behaviour.
      Between-object coding may be linked to the dorsal visual system while parallel
      coding of parts within objects takes place in the ventral system, although there
      may additionally be some dorsal involvement either when attention must be shifted
      within objects or when explicit spatial coding of parts is necessary for object
      identification.

PMID- 9770229
TI  - Neural coding of 3D features of objects for hand action in the parietal cortex of
      the monkey.
AB  - In our previous studies of hand manipulation task-related neurons, we found many
      neurons of the parietal association cortex which responded to the sight of three
      dimensional (3D) objects. Most of the task-related neurons in the AIP area (the
      lateral bank of the anterior intraparietal sulcus) were visually responsive and
      half of them responded to objects for manipulation. Most of these neurons were
      selective for the 3D features of the objects. More recently, we have found
      binocular visual neurons in the lateral bank of the caudal intraparietal sulcus
      (c-IPS area) that preferentially respond to a luminous bar or place at a
      particular orientation in space. We studied the responses of axis-orientation
      selective (AOS) neurons and surface-orientation selective (SOS) neurons in this
      area with stimuli presented on a 3D computer graphics display. The AOS neurons
      showed a stronger response to elongated stimuli and showed tuning to the
      orientation of the longitudinal axis. Many of them preferred a tilted stimulus in
      depth and appeared to be sensitive to orientation disparity and/or width
      disparity. The SOS neurons showed a stronger response to a flat than to an
      elongated stimulus and showed tuning to the 3D orientation of the surface. Their
      responses increased with the width or length of the stimulus. A considerable
      number of SOS neurons responded to a square in a random dot stereogram and were
      tuned to orientation in depth, suggesting their sensitivity to the gradient of
      disparity. We also found several SOS neurons that responded to a square with
      tilted or slanted contours, suggesting their sensitivity to orientation disparity
      and/or width disparity. Area c-IPS is likely to send visual signals of the 3D
      features of an object to area AIP for the visual guidance of hand actions.

PMID- 9770228
TI  - Human cortical mechanisms of visual attention during orienting and search.
AB  - Functional anatomical studies indicate that a set of neural signals in parietal
      and frontal cortex mediates the covert allocation of attention to visual
      locations across a wide variety of visual tasks. This frontoparietal network
      includes areas, such as the frontal eye field and supplementary eye field. This
      anatomical overlap suggests that shifts of attention to visual locations of
      objects recruit areas involved in oculomotor programming and execution. Finally,
      the fronto-parietal network may be the source of spatial attentional modulations
      in the ventral visual system during object recognition or discrimination.

PMID- 9770231
TI  - Action-based mechanisms of attention.
AB  - Actions, which have effects in the external world, must be spatiotopically
      represented in the brain. The brain is capable of representing space in many
      different forms (e.g. retinotopic-, environment-, head- or shoulder-centred), but
      we maintain that actions are represented in action-centred space, meaning that,
      at the cellular level, the direction of movement is defined by the activity of
      cells. In reaching, for example, object location is defined as the direction and
      distance between the origin of the hand and the target. Most importantly, we
      argue that more than one task-relevant action can be evoked at any moment in
      time. Therefore, highly efficient selection processes that accurately link vision
      and action have had to evolve. Research is reviewed which supports the notion of
      action-based inhibitory mechanisms that select the target from competing
      distractors.

PMID- 9770230
TI  - Neuropsychological studies of perception and visuomotor control.
AB  - According to recent conceptualizations, there are two separate cortical visual
      systems--each with its own distinctive cortical and subcortical links--and these
      two systems respectively serve the functions of perception and of motor control.
      These ideas have been arrived at through a confluence of neuroanatomical,
      electrophysiological, behavioural, and neuropsychological research. It is
      proposed that this distinction between two broad purposes of vision and their
      neural bases can provide useful working procedures for analysing both: (i) the
      nature of visuomotor processing in the normal brain; and also (ii) the abnormal
      patterns of visual processing that are seen in certain neurological conditions.

PMID- 9770232
TI  - [Mechanisms of nuclear mRNA editing].

PMID- 9770233
TI  - [Small nucleolar RNA].

PMID- 9770235
TI  - [DNA vaccines].

PMID- 9770234
TI  - [Phytochrome-like photoreceptor systems in cyanobacteria].

PMID- 9770236
TI  - [Antisense strategy--new trends].

PMID- 9770238
TI  - [Vaults: forgotten organelles rediscovered].

PMID- 9770237
TI  - [ABC transporters in human cells].

PMID- 9770239
TI  - [G proteins--the most important cellular messengers?].

PMID- 9770240
TI  - [Signalling function of G proteins insensitive to PTX in the cell].

PMID- 9770241
TI  - Functional imaging of the brain by infrared radiation (thermoencephaloscopy).
AB  - A technique for thermal imaging of the animal and human brain cortex using an
      infrared optical system is described. Thermoencephaloscopy (TES) is based on
      improved thermovision and image processing techniques and allows two-dimensional,
      contact-free, dynamic and non-invasive recording of background and evoked
      cortical activity through an unopened skull. Activated (heated) and deactivated
      (cooled) zones of the cerebral cortex are revealed. The instrumental temporal
      resolution of TES is 40 msec (25 maps sec-1), the spatial resolution is up to 70
      x 70 microns pixel-1. The diameter of the smallest recordable active region of
      the cortex is 200-300 microns. TES allows to detect the position, size and
      sequence of activation of precisely located specific cortical zones, and to
      measure their dynamics before, during and after sensory and direct cortical
      stimulation, motor acts and conditioning (associative learning). TES effects were
      recorded in rats, rabbits, cats, monkeys and humans. Waves were found spreading
      over the cortex with a speed up to 33 mm sec-1 along trajectories specific for
      the sensory modality and the site of stimulation. Some pathological processes in
      the brain are detectable by TES: spreading depression; stress; catalepsy;
      experimental tumors; and epileptic focuses. The main mechanisms of thermal
      responses recorded by TES are discussed: neural activity; local metabolism of
      units; local cerebral blood flow; and thermoconductivity in the activated zones
      of the cortex. Thermoencephaloscopy is a dynamic, non-invasive, contact-free,
      comparatively cheap, simple and inexpensive method of neuroimaging with a
      relatively high temporal and spatial resolution and sensitivity. It can be a
      useful tool in basic neuroscience and medicine.

PMID- 9770242
TI  - The role of tumour necrosis factor, interleukin 6, interferon-gamma and inducible
      nitric oxide synthase in the development and pathology of the nervous system.
AB  - Proinflammatory cytokines, tumour necrosis factor (TNF)-alpha, interferon (IFN)
      gamma and interleukin (IL)-6, have multiple effects in the central nervous system
      (CNS) not strictly cytotoxic being involved in controlling neuronal and glial
      activation, proliferation, differentiation and survival, thus influencing
      neuronal and glial plasticity, degeneration as well as development and
      regeneration of the nervous system. Moreover, they can contribute to CNS
      disorders, including multiple sclerosis. Alzheimer's disease and human
      immunodeficiency virus-associated dementia complex. Recent results with deficient
      mice in the expression of those cytokines indicate that they are in general more
      sensible to insults resulting in neural damage. Some of the actions induced by
      TNF-alpha, and IFN-gamma, including both beneficial and detrimental, are mediated
      by inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO) production.
      NO produced by iNOS may be beneficial by promoting the differentiation and
      survival of neurons. IL-6 does not induce iNOS, explaining why this cytokine is
      less often involved in this dual role protection pathology. Some of the
      proinflammatory as well as the neurotrophic effects of those cytokines also
      involve upregulation of cell adhesion molecules (CAM). Those apparently
      conflicting results may be reconciled considering that proinflammatory cytokines
      are involved in promoting the disease, mostly by inducing expression of CAM
      leading to alteration of the blood-brain barrier integrity, whereas they have a
      protective role once disease is established due to its immunosuppressive or
      neurotrophic role. Understanding the dichotomy pathogenesis/neuroprotection of
      those cytokines may provide a rationale for better therapeutic strategies.

PMID- 9770243
TI  - Spinal cord injury in the rat.
AB  - Only limited therapeutic measures are currently available for the treatment of
      spinal cord injury. This review describes the pathologic mechanisms of trauma
      induced spinal cord injury in rats, which will contribute to new understanding of
      the pathologic process leading to spinal cord injury and to further development
      of new therapeutic strategies. Spinal cord injury induced by trauma is a
      consequence of an initial physical insult and a subsequent progressive injury
      process that involves various pathochemical events leading to tissue destruction;
      the latter process should therefore be a target of pharmacological treatment.
      Recently, activated neutrophils have been shown to be implicated in the latter
      process of the spinal cord injury in rats. Activated neutrophils damage the
      endothelial cells by releasing inflammatory mediators such as neutrophil elastase
      and oxygen free radicals. Adhesion of activated neutrophils to the endothelial
      cell could also play a role in endothelial cell injury. This endothelial cell
      injury could in turn induce microcirculatory disturbances leading to spinal cord
      ischemia. We have found that some therapeutic agents that inhibit neutrophil
      activation alleviate the motor disturbances observed in the rat model of spinal
      cord injury. Methylprednisolone (MPS) and GM1 ganglioside, which are the only two
      pharmacological agents currently clinically available for treatment of acute
      spinal cord injury, do not inhibit neutrophil activation in this rat model. Taken
      together, these observations raise a possibility that other pharmacological
      agents that inhibit neutrophil activation used in conjunction with MPS or GM1
      ganglioside may have a synergistic effect in the treatment of traumatic spinal
      cord injury in humans.

PMID- 9770244
TI  - Oxidative damage in the central nervous system: protection by melatonin.
AB  - Melatonin was recently reported to be an effective free radical scavenger and
      antioxidant. Melatonin is believed to scavenge the highly toxic hydroxyl radical,
      the peroxynitrite anion, and possibly the peroxyl radical. Also, secondarily, it
      reportedly scavenges the superoxide anion radical and it quenches singlet oxygen.
      Additionally, it stimulates mRNA levels for superoxide dismutase and the
      activities of glutathione peroxidase, glutathione reductase and glucose-6
      phosphate dehydrogenase (all of which are antioxidative enzymes), thereby
      increasing its antioxidative capacity. Also, melatonin, at least at some sites,
      inhibits nitric oxide synthase, a pro-oxidative enzyme. In both in vivo and in
      vitro experiments melatonin has been shown to reduce lipid peroxidation and
      oxidative damage to nuclear DNA. While these effects have been observed primarily
      using pharmacological doses of melatonin, in a small number of experiments
      melatonin has been found to be physiologically relevant as an antioxidant as
      well. The efficacy of melatonin in inhibiting oxidative damage has been tested in
      a variety of neurological disease models where free radicals have been implicated
      as being in part causative of the condition. Thus, melatonin has been shown
      prophylactically to reduce amyloid beta protein toxicity of Alzheimer's disease,
      to reduce oxidative damage in several models of Parkinson's disease (dopamine
      auto-oxidation, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6
      hydroxydopamine), to protect against glutamate excitotoxicity, to reduce ischemia
      reperfusion injury, to lower neural damage due to gamma-aminolevulinic acid
      (phorphyria), hyperbaric hyperoxia and a variety of neural toxins. Since
      endogenous melatonin levels fal 1 markedly in advanced age, the implication of
      these findings is that the loss of this antioxidant may contribute to the
      incidence or severity of some age-associated neurodegenerative diseases.

PMID- 9770245
TI  - The bezoaric effect: working with traumatic process.

PMID- 9770246
TI  - Lesbian sexuality/female sexuality: searching for sexual subjectivity.

PMID- 9770247
TI  - Freud's treatment of the "Rat Man": a polemic with his critics.

PMID- 9770248
TI  - Freud, Yvette Guilbert, and the psychology of performance: a biographical note.

PMID- 9770249
TI  - Meaning and metaphor in psychoanalytic education.

PMID- 9770250
TI  - Ego autonomy and the healthy personality: psychodynamics, cognitive style, and
      clinical applications.

PMID- 9770251
TI  - The Environmental Rating Scale (ERS): a measure of the quality of the residential
      environment for adults with autism.
AB  - This study used classical test theory to assess the psychometric properties of
      the Environmental Rating Scale (ERS), a measure specifically designed to assess
      the treatment programs in residential settings that serve individuals with
      autism. Results of the confirmatory factor analysis support the presence of a
      single factor represented by the total score. The reliability of the measure was
      demonstrated by assessments of the internal consistency, stability, and
      interrater reliability. Preliminary analysis of the validity of the ERS indicates
      that this measure discriminates between treatment settings designed specifically
      for individuals with autism and those designed for other populations of
      developmentally handicapped clients and family homes. The ERS was also
      significantly positively correlated with a measure of the caregiver's knowledge
      about autism and a visitor's global impression of the desirability of the setting
      as a place to live.

PMID- 9770252
TI  - On the establishing and reinforcing effects of termination of demands for
      destructive behavior maintained by positive and negative reinforcement.
AB  - The results of functional analyses suggested that the destructive behavior of two
      individuals was sensitive to escape and attention as reinforcement. In an
      instructional context, we evaluated the effects of reinforcing compliance with
      functional reinforcers when destructive behavior produced a break. For one
      participant we also evaluated the effects of reinforcing compliance with
      functional reinforcers when destructive behavior produced no differential
      consequence (escape extinction). We hypothesized that destructive behavior failed
      to decrease in an instructional context when compliance resulted in a break
      because presentation of a break evoked attention-maintained destructive behavior.
      The results of a reinforcer assessment supported this hypothesis by demonstrating
      that demands functioned as positive reinforcement when no alternative activities
      were available. These results are discussed in terms of the importance of
      establishing operations in determining the appetitive or aversive properties of
      stimuli when destructive behavior is multiply controlled.

PMID- 9770253
TI  - Simultaneous and delayed matching to sample in gesture users and speakers with
      mental retardation.
AB  - Sixty-eight participants with severe mental retardation participated in a study
      of representational matching to sample. Participants were asked to match objects
      to identical objects, line drawings, miniature objects (icons), pantomimes, and
      spoken names. Participants who were successful in these matching tasks also
      experienced delayed matching tasks. Participants differed in their expressive
      communication and comparisons were made between symbolic (speaking) individuals,
      distal gesture users, and contact gesture users. Contact gesture users were
      significantly worse on identical matching to sample tasks than other
      participants. Mean scores on matching objects to line drawings were significantly
      better than mean scores on other matching tasks. In delayed matching, however,
      scores for matching objects to spoken names were significantly better than other
      tasks. The implications of these results for learning to use an augmentative
      communication device are discussed.

PMID- 9770254
TI  - Aggression and psychopathology in persons with severe or profound mental
      retardation.
AB  - We examined aggression and psychopathology in persons with severe or profound
      mental retardation. Most aggressive episodes were directed toward other clients,
      and ratings of aggression were positively correlated with self-injury,
      stereotypic behavior, and being ambulatory. In a linear regression analysis of
      psychopathological correlates, aggression was most consistently predicted by
      dependent personality and psychosis. To better describe the construct of
      aggression, we also developed an Aggression-psychopathology scale. Persons with
      mental retardation and aggression were more likely to be impulsive, attention
      seeking, dependent, socially inadequate, and anxious. Intensive efforts to modify
      the psychopathological correlates of aggression may improve treatment planning
      and outcome.

PMID- 9770256
TI  - Definitions, causes, course, and prognosis of chronic obstructive pulmonary
      disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a common disorder that is related
      to smoking in susceptible individuals. The epidemiology is complex and includes
      both environmental and host factors. Early identification and intervention via
      smoking cessation and possibly the augmentation of antioxidant defenses in the
      lung offer hope to prevent and forestall premature morbidity and mortality for
      this fourth most common cause of death in the United States.

PMID- 9770255
TI  - An analysis of maladaptive behaviors in persons with autism, PDD-NOS, and mental
      retardation.
AB  - In this study, we examined three maladaptive behaviors, self-injurious behavior
      (SIB), stereotypies, and aggression in adults with autism, pervasive
      developmental disorder, not otherwise specified (PDD-NOS), and mental
      retardation. We used a brief functional analysis rating scale. The Questions
      About Behavioral Functions (QABF), to examine the function of each behavior.
      Across the three groups, our results indicated that aggression was primarily
      maintained for attentional reasons and stereotypies for nonsocial reasons. No
      specific function(s) were found to maintain SIB. These results suggest that the
      function of a maladaptive behavior may be associated more with the particular
      maladaptive behavior displayed rather than inclusion in a certain diagnostic
      group. Implications of findings for assessment and treatment issues are
      discussed.

PMID- 9770257
TI  - Pathophysiology of chronic obstructive pulmonary disease.
AB  - The prevalence of COPD has increased as mortality from the two organ systems
      affected by the same risk factors of smoking, heart attacks and strokes, has
      decreased. Once diagnosed, COPD is progressive and may lead to disability,
      usually due to dyspnea, at a relatively early age (60 to 80 years of age). COPD
      is usually caused by destruction of the lung parenchyma or by disease affecting
      the airways. In most patients both processes exist simultaneously. Less often
      recognized is the fact that the disease does not affect all portions of the lung
      alike, which causes different physiologic behaviors in different parts of the
      lung. This article integrates the pathologic changes of COPD with the known
      adaptive and maladaptive consequences of those changes. An understanding of these
      changes should result in an increased capacity to comprehend the different
      therapeutic strategies that have been developed to decrease the symptoms and
      improve the well-being of patients with COPD.

PMID- 9770258
TI  - Diagnosing and monitoring the clinical course of chronic obstructive pulmonary
      disease.
AB  - COPD is an extremely common, chronic disorder characterized by a reduction in
      airflow after the administration of an inhaled bronchodilator as measured by the
      FEV1. The diagnosis is suspected in patients with a history of several decades of
      cigarette smoking who present with nonspecific respiratory symptoms. The
      diagnosis is established by simple forced expiratory spirometry. Baseline
      evaluation usually includes a chest radiograph and some assessment of functional
      capacity, either by history or with some form of exercise testing. In patients
      whose initial FEV1 is more severely reduced or who have significant dyspnea, an
      arterial blood gas is indicated at baseline. Dyspnea, hypoxemia, or hypercarbia
      that is out of proportion to the measured FEV1, at either presentation or follow
      up, should prompt a thorough evaluation for complicating conditions. There are
      important roles in health care delivery and chronic disease management strategies
      for RCPs, primary care providers, and specialty trained pulmonary physicians. The
      need for repeated, extensive, or expensive testing will be largely driven by
      patients symptoms but disease monitoring with periodic assessments of dyspnea,
      functional capacity, and spirometry can be performed without great expense.

PMID- 9770260
TI  - Inpatient management of chronic obstructive pulmonary disease.
AB  - Initial steps in treating an acute exacerbation of COPD include identifying the
      underlying cause and addressing whether ICU admission is warranted. For
      nonintubated hospitalized patients, current recommendations include supplemental
      oxygen to achieve PaO2 of 60 to 65 mm Hg, inhaled bronchodilators, perhaps using
      both beta-adrenergic and anticholinergic agents, and intravenous corticosteroids.
      For patients with purulent exacerbations, antibiotics may confer benefit.
      Directed coughing to encourage secretion clearance is advised if the patient's
      spontaneous cough is inadequate. Finally, as discussed elsewhere in this issue,
      noninvasive positive pressure ventilation may lessen mortality and help avert the
      need for intubation in selected patients. Ancillary treatments include
      prophylaxis against venous thromboembolism and, as discharge nears, attention to
      updating vaccinations (e.g., pneumococcal and influenza) and to homegoing needs
      (e.g., instruction in bronchodilator administration techniques, adequacy of home
      care, and rehabilitation).

PMID- 9770259
TI  - Outpatient management.
AB  - The successful management of outpatients with COPD requires a multifaceted
      approach that includes prophylactic, palliative, and life-extending therapies.
      All patients should undergo smoking cessation, avoid potentially harmful
      environments, and receive influenza and pneumococcal vaccines at recommended
      intervals. Although medical therapy may yield only marginal benefits in patients
      with minimal airway responsiveness, even small improvements may translate into
      significant functional benefits and will be greatly appreciated. Therefore, every
      effort should be expended to optimize the patient's medical regimen and to
      ascertain that methods of delivery (such as use of spacers) are as recommended.
      Physical therapy measures may be useful in patients with copious sputum
      production, and pursed-lip and diaphragmatic breathing exercises may reduce
      dyspnea and lend a sense of control to patients with severe flow limitation.
      Oxygen therapy is the only modality demonstrated to improve survival in patients
      with severe COPD and may give symptomatic relief to some patients. Its use,
      however, is restricted to patients meeting guidelines for hypoxemia, and although
      dyspneic patients not meeting these guidelines may desire oxygen, insurers will
      decline coverage for them. Newer modalities, such as noninvasive ventilation, may
      improve gas exchange and quality of life in some patients with hypercapnia and
      nocturnal oxygen desaturations, but subgroups of COPD patients who benefit have
      not been well-defined, and pending further investigation, guidelines for use
      should be considered tentative. Patients should be encouraged to enter a
      comprehensive rehabilitation program, but if one is unavailable or the patient
      declines, a rehabilitation approach should be applied. Practitioners should
      attempt to educate patients at each visit, offering advice not only on
      medications, but also on regular exercise, good nutrition, and ways of coping
      psychologically with chronic illness. By taking such a comprehensive and caring
      approach, and being available to assist with problems and crises, the
      practitioner can help to enhance the quality and length of the COPD patient's
      life.

PMID- 9770261
TI  - Mechanical ventilation of the patient with chronic obstructive pulmonary disease.
AB  - Mechanical ventilation of the patient with COPD is a balance between avoiding
      overdistension, auto-PEEP, providing adequate gas exchange, and allowing patient
      ventilator synchrony. Figure 13 shows an approach that the authors have found
      helpful to achieve these goals.

PMID- 9770262
TI  - Maximizing functional capacity. Pulmonary rehabilitation and adjunctive measures.
AB  - Pulmonary rehabilitation has become an important adjunct to standard medical
      therapy, with the primary goal of restoring patients to the highest possible
      functional state using a combination of exercise training, education, respiratory
      and chest physiotherapy techniques, and psychosocial support. Evidence supports
      the use of this combined modality therapy for motivated patients with disability
      from chronic lung disease. Although pulmonary function generally does not change,
      exercise tolerance can improve, together with decreased symptoms of
      breathlessness, improved quality of life, and less need for health care services.
      Patients are empowered with a better understanding of their disease and the
      proper usage of medications, oxygen therapy, and chest physiotherapy techniques.
      Thus, pulmonary rehabilitation enables patients to make the most of their lungs
      and their life.

PMID- 9770263
TI  - Sleep-related disorders and chronic obstructive pulmonary disease.
AB  - Sleep-disordered breathing is ubiquitous in COPD. Sleep-related hypoxemia results
      from hypoventilation attributable to reduced respiratory drive and abnormal
      mechanics, and from probable changes in V/Q matching. An overlap syndrome
      combining COPD and OSA also has been described. Disturbances in cardiac,
      hematologic, and pulmonary function, as well as sleep complaints, are common when
      COPD is complicated by nocturnal hypoxemia, and these sequelae are even more
      common when COPD and OSA coexist. Treatment with oxygen is the mainstay for COPD
      and sleep desaturation alone, whereas combined nasal CPAP and oxygen are most
      frequently used for the overlap syndrome.

PMID- 9770265
TI  - End-of-life ethical issues.
AB  - COPD is a progressive disorder characterized by intermittent episodes of acute
      exacerbations, each of which has the potential for producing respiratory failure
      and a need for mechanical ventilation. The decision to intubate a patient with
      severe underlying COPD requires a blending of the physician's estimation of
      prognosis with the patient's life goals, values, and self-perceived quality of
      life. Decisions regarding intubation and life support are aided by initiating a
      patient-caregiver dialogue during periods of good or stable health before a
      medical crisis occurs. These discussions can inform patients about the likely
      outcome of life support and promote meaningful and valid advance directives.

PMID- 9770264
TI  - Surgical approaches to advanced emphysema.
AB  - The care of patients with advanced emphysema requires an understanding of both
      medical and surgical therapy for this disease. Current surgical approaches to
      advanced emphysema include bullectomy, lung volume reduction surgery, and lung
      transplantation. Each procedure is applicable to a specific subset of patients.
      This article reviews the evaluation and selection of patients for each procedure,
      as well as operative and postoperative management, mechanisms by which surgery
      improves function, and overall outcomes after each procedure.

PMID- 9770266
TI  - Cloning and genetic mapping of zebrafish BMP-2.
AB  - The BMP family of polypeptide growth factors has been shown to play diverse roles
      in establishing embryonic patterning and tissue fates. We report the cloning of
      the zebrafish homologue of BMP-2, examine its expression during embryogenesis,
      and find that it is localized to the distal end of the long arm of zebrafish
      chromosome 20. A missense mutation of the bmp2 gene has recently been shown to be
      responsible for the early dorsalized phenotype of the zebrafish swirl mutant
      [Kishimoto et al., 1997]. Given the dynamic expression of bmp2 in the developing
      embryo and the complex interactions of BMP signaling response in vertebrates, it
      is possible that other mutant phenotypes, due to altered bmp2 gene expression,
      will eventually map to or interact with this genetic locus.

PMID- 9770267
TI  - A homologue of the calcium-binding disulfide isomerase CaBP1 is expressed in the
      developing CNS of Drosophila melanogaster.
AB  - Previous studies identified a group of proteins localized to the endoplasmic
      reticulum (ER) that bind calcium and direct protein folding. Three of these
      proteins, CaBP1, CaBP2, and protein disulfide isomerase, have been purified from
      rat microsomes and analyzed biochemically. However, their function in vivo has
      not been determined. Here, we report the isolation of a homologue of the CaBP1
      gene from the fruitfly Drosophila melanogaster (DmCaBP1). The predicted sequence
      of the Drosophila protein is very similar to that of rat CaBP1 and retains motifs
      thought to be functionally important in the mammalian protein. We show that
      DmCaBP1 is expressed in a specific spatiotemporal pattern during embryogenesis.
      In particular, it is expressed in midline precursor cells in the developing CNS.
      This is the first demonstration of tissue-specific expression for a member of
      this group of ER proteins and suggests a possible role for DmCABP1 as a molecular
      chaperone involved in nervous system development. The identification of the
      DmCaBP1 gene provides a basis for future genetic studies of its function.

PMID- 9770268
TI  - Imprinted expression and methylation of the mouse H19 gene are conserved in
      extraembryonic lineages.
AB  - The imprinted H19 gene is hypomethylated on the active maternal allele and
      hypermethylated on the repressed paternal allele in the somatic tissues of mice
      and humans. We previously demonstrated that the paternal-specific methylation of
      a 2 kb region located between -2 and -4 kb relative to the start of transcription
      is maintained throughout murine development, and we thus propose that this region
      is crucial to determining the imprinted expression of H19. Here, we test the
      correlation between differential methylation and imprinted expression by
      analyzing the mouse H19 gene in the undermethylated extraembryonic tissues.
      During early and midpostimplantation stages, > 95% of the H19 RNA is derived from
      the maternal allele. Dissection of yolk sac revealed that the paternal allele is
      expressed at a low level in the viseral endoderm but is completely repressed in
      visceral mesoderm. Bisulfite methylation analysis of yolk sac DNA showed that the
      maternal allele was hypomethylated and that 95% of the paternally derived clones
      were hypermethylated. Thus in extraembryonic lineages, the majority of H19 DNA is
      differentially methylated. These results lend further support to the hypothesis
      that DNA methylation confers the imprint on H19.

PMID- 9770269
TI  - cis-Acting sequences controlling the adult-specific transcription pattern of the
      Drosophila affinidisjuncta Adh gene.
AB  - The cis-acting sequences required for the adult-specific expression pattern of
      the alcohol dehydrogenase (Adh) gene of the Hawaiian picture-winged fruit fly,
      Drosophila affinidisjuncta were analyzed by germline transformation. Normally
      this gene produces two developmentally regulated transcripts. The upstream
      (distal) promoter produces a distal transcript, which makes up about 80% of the
      total in adults, while the downstream (proximal) promoter produces a
      corresponding proximal transcript, which accounts for the remainder. Previously
      constructed genes lacking regions corresponding to regulatory elements within the
      Drosophila melanogaster Adh gene or regions known to be required for full
      expression of the D. affinidisjuncta Adh gene in larvae were analyzed by
      introduction into the germline of D. melanogaster followed by RNase-protection
      analysis of RNA levels. In addition, to test a model of preferential promoter
      utilization by which transcription at the proximal promoter is inhibited by
      transcription initiated at the upstream distal promoter, a construction lacking
      the distal promoter was analyzed. Sequences homologous to the adult enhancer of
      the Adh gene of D. melanogaster appear to play a similar role in the D.
      affinidisjuncta gene. In contrast to what has been reported for other Drosophila
      Adh genes, this and some other regulatory elements are shared by the two
      promoters of the D. affinidisjuncta gene. Taken together, the results favor a
      model of stage-specific switching between the two promoters of the D.
      affinidisjuncta gene that involves competition for limiting components
      stimulating transcription, rather than interference by read-through from the
      upstream promoter.

PMID- 9770270
TI  - Cloning of zebrafish vsx1: expression of a paired-like homeobox gene during CNS
      development.
AB  - vsx1 is a homeobox gene encoding a paired-type homeodomain and a CVC domain that
      was originally cloned from an adult goldfish retinal library. We previously
      reported the spatiotemporal expression pattern of vsx1 in the adult and
      developing retina of zebrafish and goldfish, and we suggested that vsx1 plays a
      role in determining the cell fate and maintenance of retinal interneurons. Other
      related genes encoding a CVC domain, such as vsx2 (alx) and chx10, are expressed
      both within and outside the retina during development. In this study, we report
      the cloning of zebrafish vsx1 and its developmental expression in both retinal
      and nonretinal regions of the CNS in zebrafish embryos. vsx1 expression was
      detected in a subset of hindbrain and spinal cord neurons before it was expressed
      in the retina. At about the same time that retinal expression began, the level of
      vsx1 was decreased in the spinal cord. The expression of vsx1 was progressively
      restricted, and eventually it was detected only in the inner nuclear layer (INL)
      of the developing retina. The combined expression patterns of teleost vsx1 and
      vsx2 (alx) during early zebrafish development encompasses the expression pattern
      observed for murine Chx10, and indicates a partitioning of function for CVC genes
      in lower vertebrates.

PMID- 9770271
TI  - Abortive conjugation induced by UV-B irradiation at meiotic prophase in
      Tetrahymena thermophila.
AB  - Conjugating Tetrahymena were irradiated by ultraviolet-B (UV-B) at various stages
      of conjugation. When the conjugants were exposed to the UV-B at late meiotic
      prophase (the stage from pachytene to diplotene), abortive conjugation was
      induced a high frequencies. After completing meiosis, a significant number of the
      conjugants showed marked anomalies, i.e., failure of nuclear selection after
      meiosis, and abortion of the subsequent conjugation process such as a postmeiotic
      division to form gametic nuclei, nuclear exchange, synkaryon formation, and
      postzygotic development. The conjugating pairs retained the parental macronucleus
      and separated earlier as compared with a control. The resultant exconjugants
      degenerated meiotic products and became amicronucleates. These observations
      strongly suggest the presence of a UV-sensitive molecule that is expressed
      specifically at the meiotic prophase and that directs the subsequent development
      after meiosis.

PMID- 9770272
TI  - Reverse transcription-PCR analysis of the regulation of ethylbenzene dioxygenase
      gene expression in Pseudomonas fluorescens CA-4.
AB  - Pseudomonas fluorescens strain CA-4 is a bioreactor isolate previously
      characterised by the presence of a side chain oxidation pathway for ethylbenzene
      breakdown. In this report a second pathway involving ethylbenzene ring
      dioxygenation has been identified in this strain. We examine here second
      substrate inhibition of the genes encoding the initial enzymes of this pathway,
      using reverse transcription (RT)-PCR. The genes of the ring-dioxygenation have
      been cloned and sequenced. They exhibit near identity to the gene clusters
      encoding the aromatic ring dioxygenase enzymes of two previously described
      isopropyl degrading strains, Pseudomonas sp. strain JR1 and P. fluorescens IP01.
      This dioxygenase pathway appears to be the major pathway for ethylbenzene
      degradation in this strain. The expression of these genes appears to be affected
      by the presence of second carbon substrates. Using RT-PCR we demonstrate that the
      negative effect of glutamate present in the growth medium together with
      ethylbenzene on the rate of ethylbenzene metabolism is mediated at the
      transcriptional level on the ethylbenzene dioxygenase genes.

PMID- 9770273
TI  - Characterisation of the bacteriophage T4 comC alpha 55.6 and comCJ mutants. A
      possible role in an antitermination process.
AB  - We have performed a new screen for T4 mutants (comC) that overcome the phage
      growth restriction caused by the Escherichia coli rho/tabC mutants. We show that
      one such mutant (comCJ) identifies a different gene from that identified by
      canonical comC mutants. We compare the regulation of T4 prereplicative
      transcription in a rho/tabC mutant infected by T4 wild-type, by a canonical comC
      mutant (comC alpha 55.6) and by comCJ. The transcription rates of the two
      prereplicative genes 39 and 43 is depressed in a T4 wild-type infected tabC host
      mutant. When comC alpha 55.6 and/or comCJ single and double mutants are the
      infecting phages, transcription of genes 39 and 43 is resumed to different
      extents; in particular, in the double mutant infections there appears to be a
      synergistic effect on transcription. Furthermore, we find that the comC alpha
      55.6 phage mutant affects the transcription rate of the gene rIIA in a wild-type
      host.

PMID- 9770274
TI  - Purification and characterization of cystathionine gamma-lyase from Lactobacillus
      fermentum DT41.
AB  - A homo-tetrameric ca. 140-kDa cystathionine gamma-lyase was purified to
      homogeneity from Lactobacillus fermentum DT41 by four chromatographic steps. This
      was the first enzyme responsible for amino acid catabolism purified from
      lactobacilli. The activity is pyridoxal-5'-phosphate dependent and the enzyme
      catalyzes the alpha,gamma-elimination reaction of L-cystathionine producing L
      cysteine, ammonia and alpha-ketobutyrate. The cystathionine gamma-lyase produced
      a free thiol group, a keto acid component and ammonia from several amino acids,
      including L-cysteine and methionine, and amino acid derivatives. L-Cystine was
      the best substrate. The enzyme was stable in the conditions of cheese ripening
      and may contribute to the biosynthesis of sulfur-containing compounds.

PMID- 9770275
TI  - Producer self-protection against the lantibiotic epidermin by the ABC transporter
      EpiFEG of Staphylococcus epidermidis Tu3298.
AB  - Self-protection of the epidermin-producing strain Staphylococcus epidermidis
      Tu3298 against the pore-forming lantibiotic epidermin is mediated by an ABC
      transporter composed of the EpiF, EpiE, and EpiG proteins. We developed a
      sensitive assay based on HPLC analysis to investigate the capacity of the EpiFEG
      transporter to release epidermin and analogues from the cell surface to the
      external fluid. Our results indicate that the EpiFEG transporter works by
      expelling the lantibiotic from the cytoplasmic membrane into the surrounding
      medium. Analysis of transporter efficacy using nisin and gallidermin derivatives
      as substrates revealed a high substrate specificity. Furthermore, we showed that
      the activity of the gallidermin derivative L6G is enhanced by the presence of
      EpiE.

PMID- 9770276
TI  - Activation of a consensus FNR-dependent promoter by DNR of Pseudomonas aeruginosa
      in response to nitrite.
AB  - Expression of the enzymes for anaerobic nitrate respiration of Pseudomonas
      aeruginosa requires two CRP/FNR-related transcriptional regulators, ANR and DNR.
      Activity of the consensus CRP- or FNR-dependent promoter in the anr and dnr
      deficient mutants was investigated. The CRP-dependent promoter was active in the
      mutant strains. Both regulators could activate the promoter with a consensus FNR
      binding motif. DNR-dependent activation was nitrite-dependent, whereas activation
      by ANR was not, suggesting that only DNR is involved in sensing nitrogen oxides.

PMID- 9770277
TI  - Response of the NAD(P)H-oxidising flavohaemoglobin (Hmp) to prolonged oxidative
      stress and implications for its physiological role in Escherichia coli.
AB  - The Escherichia coli flavohaemoglobin (Hmp) has a globin-like N-terminal domain
      and a ferredoxin-NADP-reductase-like C-terminal domain. We show here that
      purified Hmp oxidises both NADH and NADPH with Km values of 1.8 and 19.6 microM,
      respectively. Prolonged incubation of a hmp-lacZ fusion strain with the redox
      cycling agent paraquat resulted in a 28-fold induction of hmp gene expression,
      nearly 3-fold higher than after short periods of exposure. A strain overproducing
      Hmp was significantly more sensitive to paraquat than was the wild-type strain
      but, in vitro, purified Hmp was not an effective NADPH-paraquat diaphorase.
      Prolonged incubation of a wild-type strain with paraquat increased intracellular
      Hmp to spectrally detectable levels.

PMID- 9770278
TI  - A human transferrin-binding protein of Staphylococcus aureus is immunogenic in
      vivo and has an epitope in common with human transferrin receptor.
AB  - To understand human immune responses against the human transferrin-binding
      protein of Staphylococcus aureus (SA-tbp), we examined cell wall proteins from S.
      aureus ATCC 6538 using human convalescent sera, and a monoclonal antibody
      specific for human transferrin receptor (McAb-HTR). The SA-tbp, detected by
      immunoblot assay, was iron-repressible, reacted with the convalescent sera, and
      cross-reacted with McAb-HTR. Immunoelectron microscopy probed with McAb-HTR
      showed a reaction zone around the test strain from the deferrated BHI. After
      being preincubated with an S. aureus-bacteremic serum, the electroblot of the SA
      tbp still reacted with McAb-HTR, but not with human transferrin-horseradish
      peroxidase conjugate. We conclude, there are at least two kinds of epitopes in
      the SA-tbp; one able to bind to human transferrin is immunogenic in humans, but
      the other sharing epitopes common with human transferrin receptor is not
      immunogenic in humans.

PMID- 9770279
TI  - Enhancement of in vitro cytopathogenicity by Acanthamoeba spp. following
      acquisition of bacterial endosymbionts.
AB  - Approximately one in five isolates of Acanthamoeba spp. recovered from clinical
      and environmental sources are found to harbor obligate, uncultured bacterial
      endosymbionts of unknown clinical significance. To investigate their possible
      role in amoebic pathogenesis, four uninfected amoebic strains were exposed to
      four different endosymbionts, from which 12 stably-infected host-symbiont pairs
      resulted. Standardized inocula of amoebae with and without endosymbionts were
      placed on fibroblast monolayers to examine for cytopathic effects (CPEs). Eight
      to 10 days were required for monolayer effacement by endosymbiont-free amoebae; 5
      8 days for amoebae containing Gram-negative rod endosymbionts; and 3 days for two
      amoebic isolates infected with a Chlamydia-like endosymbiont. All endosymbiont
      infected amoebae produced a statistically significant enhancement in CPEs in
      comparison to uninfected amoebae; endosymbionts alone on monolayers produced no
      CPEs. This report provides evidence that obligate bacterial endosymbionts are
      able to enhance amoebic pathogenic potential in vitro by some as-yet unknown
      mechanism.

PMID- 9770280
TI  - Protein expression by Streptococcus uberis in co-culture with bovine mammary
      epithelial cells.
AB  - Three strains of Streptococcus uberis isolated from dairy cows with mastitis were
      co-cultured with a bovine mammary epithelial cell line (MAC-T) in Dulbecco's
      modified Eagle's medium without fetal bovine serum. Protein profiles from culture
      supernatants and bacterial pellets among different treatments were compared by
      electrophoresis. There were proteins induced or having increased expression in
      both supernatant and surface-associated samples from S. uberis co-cultured with
      MAC-T cells. Some of these proteins were recognized by antibodies in serum
      obtained from a cow infected by S. uberis. In supernatant samples, there were two
      distinct protein bands at 35 and 36.8 kDa for all three strains of S. uberis co
      cultured with MAC-T cells. These two bands were absent when bacterial protein
      synthesis was inhibited by chloramphenicol. This study clearly indicates that
      bacterial protein expression was regulated in response to co-culture with mammary
      epithelial cells.

PMID- 9770281
TI  - Identification of iron-regulated outer membrane proteins in uropathogenic Proteus
      mirabilis and its relationship with heme uptake.
AB  - The effect of iron deprivation on the expression of outer membrane proteins and
      the ability to use heme as an iron source by uropathogenic Proteus mirabilis, Pr
      6515, was studied. Examination of iron-restricted bacteria showed three outer
      membrane proteins ranging from 66 to 75 kDa to be affected by iron restriction,
      as well as a newly expressed 64-kDa protein. These proteins were induced within
      15 minutes of iron-deprivation. The strain grew in the presence of ferric
      citrate, hemin and hemoglobin as iron sources, but could not use transferrin,
      lactoferrin or siderophores from exogenous sources. The 64- and 66-kDa proteins
      showed hemin-binding activity by affinity chromatography, and both reacted in
      Western blots with sera from mice transurethrally infected with the same strain.
      We suggest that P. mirabilis expresses iron-regulated outer membrane proteins
      that could be involved in heme uptake and may have a role in pathogenesis.

PMID- 9770282
TI  - The ability to bind albumin is correlated with nitric oxide sensitivity in
      Moraxella catarrhalis.
AB  - Moraxella catarrhalis is sensitive to NO generators, e.g. S-nitroso-N
      acetylpenicillamine (SNAP) and sodium nitroprusside (SNP), but can spontaneously
      develop higher SNP tolerance. Using SDS-PAGE of outer membrane proteins and
      immunoblotting for serum albumin, we found that the wild strain bound more blood
      medium-derived albumin than the SNP-resistant variant did. There was a negative
      correlation between NO tolerance and the presence of serum albumin in the medium.
      We suggest that M. catarrhalis can change its surface properties to avoid binding
      albumin and thereby increase its resistance to NO. Growth of Moraxella is
      affected by iron, and that may have influenced our results. Using chrome azurol S
      plates as an indicator, we noted that both albumin and SNP have a strong affinity
      for iron(III).

PMID- 9770283
TI  - Salicylate inhibits fimbriae mediated HEp-2 cell adherence of and
      haemagglutination by enteroaggregative Escherichia coli.
AB  - Enteroaggregative Escherichia coli (EAggEC) are associated with both acute and
      persistent diarrhoea in children. Bowel colonisation due to fimbrial adherence
      factors appears to play a major role in the disease process. In this study, we
      investigated the effect of sodium salicylate and 5-aminosalicylic acid on
      adherence of a type strain and 40 clinical isolates of EAggEC to HEp-2 cells and
      erythrocytes from different species. Growth in the presence of 10 mM salicylate
      resulted in markedly decreased adherence to tissue culture cells with 33/40
      (82.5%) isolates, and was also associated with inhibition of haemagglutination in
      20/33 (60.6%) isolates. Complete or partial inhibition of adherence was also seen
      in two of five isolates showing localised adherence and three of five isolates
      with diffuse adherence. Decrease in adherence was associated with decreased or
      absent expression of fimbriae in 28/40 (70%) of the EAggEC isolates, although
      production of outer membrane proteins was not affected. Salicylates appear to
      inhibit adherence mediated by fimbrial adhesins.

PMID- 9770284
TI  - Glucose transport in a methylotrophic yeast Hansenula polymorpha.
AB  - Glucose transport was studied in a methylotrophic yeast Hansenula polymorpha. Two
      kinetically different glucose transport systems were revealed in cells grown
      under different growth conditions. Glucose-repressed cells exhibited a low
      affinity transport system (Km for glucose 1.75 mM) while glucose-derepressed and
      ethanol-grown cells had a high-affinity transport system (Km for glucose 0.05
      0.06 mM). The high- and low-affinity transport systems differed in substrate
      specificity, sensitivity to pH, dinitrophenol and protonophore carbonyl cyanide-m
      chlorophenyl-hydrazone. The kinetic rearrangement of the glucose transport system
      in response to altered growth conditions was dependent on de novo protein
      synthesis.

PMID- 9770285
TI  - The S-layer protein from Campylobacter rectus: sequence determination and
      function of the recombinant protein.
AB  - The gene encoding the crystalline surface layer (S-layer) protein from
      Campylobacter rectus, designated slp, was sequenced and the recombinant gene
      product was expressed in Escherichia coli. The gene consisted of 4086 nucleotides
      encoding a protein with 1361 amino acids. The N-terminal amino acid sequence
      revealed that Slp did not contain a signal sequence, but that the initial
      methionine residue was processed. The deduced amino acid sequence displayed some
      common characteristic features of S-layer proteins previously reported. A
      homology search showed a high similarity to the Campylobacter fetus S-layer
      proteins, especially in their N-terminus. The C-terminal third of Slp exhibited
      homology with the RTX toxins from Gram-negative bacteria via the region including
      the glycine-rich repeats. The Slp protein had the same N-terminal sequence as a
      104-kDa cytotoxin isolated from the culture supernatants of C. rectus. However,
      neither native nor recombinant Slp showed cytotoxicity against HL-60 cells or
      human peripheral white blood cells. These data support the idea that the N
      terminus acts as an anchor to the cell surface components and that the C-terminus
      is involved in the assembly and/or transport of the protein.

PMID- 9770286
TI  - Extracellular proteins and other components as obligate intermediates in the
      induction of a range of acid tolerance and sensitisation responses in Escherichia
      coli.
AB  - Several acid tolerance responses of Escherichia coli were associated with
      secretion into the growth media of components (frequently proteins) which altered
      acid tolerance of other cultures. First, medium filtrates from cultures induced
      to acid tolerance by several conditions converted pH 7.0-grown organism to
      tolerance and, for most such responses, filtrate proteins were needed for full
      induction. Secondly, filtrates from cultures induced to acid sensitivity at
      alkaline pH produced sensitisation of resistant cultures. Thirdly, filtrates from
      inherently tolerant or sensitive strains altered tolerance or sensitivity of
      normal strains. In many cases, filtrate components were essential for the
      original response, e.g. acid habituation at pH 5.0. Extracellular components may
      function as intermediates only in stress tolerance responses, but other adaptive
      responses must be tested as such components may function in other inducible
      processes.

PMID- 9770287
TI  - The capsule biosynthetic locus of Pasteurella multocida A:1.
AB  - Pasteurella multocida is the aetiological agent of fowl cholera, bovine
      haemorrhagic septicaemia and atrophic rhinitis in pigs. Many strains of P.
      multocida express a capsule on their surface. However, nothing is known about the
      capsule biosynthetic locus in P. multocida although the capsule has been
      implicated as a virulence factor. The entire capsule locus of P. multocida A:1
      was cloned and sequenced. The locus is divided into three regions. Region 1
      comprises four ORFs which are involved in the transport of the capsule
      polysaccharide to the surface. Region 2 comprises five ORFs whose postulated
      protein products are involved in the biosynthesis of the polysaccharide capsule.
      Region 3 comprises two ORFs whose postulated products show similarity to proteins
      that are involved in the phospholipid substitution of the polysaccharide capsule.

PMID- 9770288
TI  - Overexpression of marA, soxS, or acrAB produces resistance to triclosan in
      laboratory and clinical strains of Escherichia coli.
AB  - Triclosan (Irgasan) is a broad spectrum antimicrobial agent used in handsoaps,
      toothpastes, fabrics, and plastics. It inhibits lipid biosynthesis in Escherichia
      coli, probably by action upon enoyl reductase (FabI) (McMurry, L.M., Oethinger,
      M. and Levy, S.B. (1988) Nature 394, 531-532). We report here that overexpression
      of the multidrug efflux pump locus acrAB, or of marA or soxS, both encoding
      positive regulators of acrAB, decreased susceptibility to triclosan 2-fold.
      Deletion of the acrAB locus increased the susceptibility to triclosan
      approximately 10-fold. Four of five clinical E. coli strains which overexpressed
      marA or soxS also showed enhanced triclosan resistance. The acrAB locus was
      involved in the effects of triclosan upon both cell growth rate and cell lysis.

PMID- 9770289
TI  - Catabolite inactivation of the maltose transporter in nitrogen-starved yeast
      could be due to the stimulation of general protein turnover.
AB  - Addition of glucose to Saccharomyces cerevisiae inactivates the maltose
      transporter. The general consensus is that this inactivation, called catabolite
      inactivation, is one of the control mechanisms developed by this organism to use
      glucose preferentially whenever it is available. Using nitrogen-starved cells
      (resting cells), it has been shown that glucose triggers endocytosis and
      degradation of the transporter in the vacuole. We now show that maltose itself
      triggers inactivation and degradation of its own transporter as efficiently as
      glucose. This fact, and the observation that glucose inactivates a variety of
      plasma membrane proteins including glucose transporters themselves, suggests that
      catabolite inactivation of the maltose transporter in nitrogen-starved cells is
      not a control mechanism specifically directed to ensure a preferential use of
      glucose. It is proposed that, in this metabolic condition, inactivation of the
      maltose transporter might be due to the stimulation of the general protein
      turnover that follows nitrogen starvation.

PMID- 9770290
TI  - Control of metabolic interconversion of isocitrate dehydrogenase between the
      catalytically active and inactive forms in Escherichia coli.
AB  - The enzymic interconversion of Escherichia coli isocitrate dehydrogenase (ICDH)
      between the catalytically active and inactive forms is mediated through the
      activities of ICDH-kinase/phosphatase in response to changes in the metabolic
      environment. In this study, the use of mutant strains devoid of isocitrate lyase
      (aceA:: Tn10) and pyruvate dehydrogenase activities revealed that the signal
      which triggers the reversible inactivation of ICDH in vivo is not directly
      related to acetate itself, but rather to the need to maintain high intracellular
      levels of isocitrate and free co-enzyme A. The use of these mutants also
      revealed, rather unexpectedly, that acetate grown cells contain more ICDH protein
      than those grown with other carbon sources and that the catalytic activity of
      ICDH kinase/phosphatase is in excess of cellular demands. Furthermore, this study
      also revealed the presence of a 50-kDa (+/- 2 kDa) acetate-specific polypeptide,
      the identity of which has yet to be established.

PMID- 9770291
TI  - Quorum-sensing and siderophore biosynthesis in Pseudomonas aeruginosa: lasR/lasI
      mutants exhibit reduced pyoverdine biosynthesis.
AB  - Cell density-dependent gene expression in Pseudomonas aeruginosa is controlled,
      in part, by the quorum-sensing regulator LasR. lasR null mutants exhibited a
      reproducible 2-fold decrease in production of the catecholate-hydroxamate
      siderophore pyoverdine during grown under iron-limiting conditions. Similarly,
      lasI mutants defective in the biosynthesis of the autoinducer PAI-1 also
      exhibited a 2-fold decrease in pyoverdine production which could be largely
      restored upon addition of exogenous PAI-1. lasR mutants were not altered with
      respect to expression of the pvdD gene involved in the synthesis of the peptide
      portion of pyoverdine, indicating that some other pyoverdine biosynthetic gene(s)
      were affected by the LasRI status of the cell. This represents the first report
      of quorum-sensing regulation of siderophore production in bacteria and highlights
      the fact that cell density, while not an essential signal for pyoverdine
      expression, does enhance production of this siderophore.

PMID- 9770292
TI  - Isolation and characterization of a porin-like protein of 45 kilodaltons from
      Bacteroides fragilis.
AB  - Resistance to the combination of amoxicillin and clavulanic acid in some
      Bacteroides fragilis strains may be associated with a lack of porin proteins.
      Comparison of outer membrane protein profiles from one resistant strain (B.
      fragilis CFPL 358) and two susceptible strains of B. fragilis (ATCC 25285 and
      CFPL 92125) showed that a few proteins were missing in the resistant strain,
      especially a 45-kDa protein. To determine whether this protein was a porin-like
      protein, we attempted to isolate it from the two susceptible strains by using gel
      filtration (Sephacryl S-200, Superose 6) and ion exchange chromatographies (DEAE
      Trisacryl, DEAE Sepharose Fast Flow). Elution from DEAE resins was poor compared
      to the 60-67-kDa region, which suggested that the 45-kDa protein exhibited
      stronger cationic forms. The use of sodium dodecyl sulfate during elution
      improved the recovery of the 45-kDa protein, showing that detergent modified its
      conformation and its ionic bounds with the chromatographic matrices but it was
      not sufficient for good purification. Superose 6 gel filtration also failed to
      separate this protein from the 60-67-kDa region. The only method resulting in the
      positive recovery of a purified 45-kDa band from both susceptible B. fragilis
      strains was electroelution from SDS-PAGE. The swelling assay showed that the 45
      kDa protein was a porin-like protein. From this study, we concluded that the 45
      kDa protein from B. fragilis was a porin-like protein which might be involved in
      the antibiotic resistance of a strain in which this protein was missing.

PMID- 9770293
TI  - The PBP 5 synthesis repressor (psr) gene of Enterococcus hirae ATCC 9790 is
      substantially longer than previously reported.
AB  - A reexamination of the nucleotide sequence of the psr gene of Enterococcus hirae
      revealed the presence of two additional nucleotides at residues 1190 and 1191. As
      a result, instead of a stop codon after 148 aa, the psr gene product would
      contain 293 aa residues. The revised size of the gene product was confirmed by
      subsequently cloning and expressing the psr gene in Escherichia coli. The derived
      amino acid sequence of the revised psr gene product was found to be similar to
      several other proteins in the combined GenBank/EMBL database. The protein
      products of some of these genes are thought to play regulatory role(s) in exo or
      capsular polysaccharide synthesis and/or in cell wall metabolism. All the
      putative homologs of the revised Psr appear to have a putative membrane-anchoring
      domain at their N-termini. Amino acid blocks with high degrees of similarity have
      been identified in the aligned sequences, and it is suggested that these common
      motifs could be of structural or functional importance.

PMID- 9770294
TI  - Cloning of a novel gene yrbB, encoding a protein located in the spore integument
      of Bacillus subtilis.
AB  - A DNA fragment (2.7 kbp) containing three deduced open reading frames, orf1, orf2
      and orf3 (partial sequence), was isolated from the genomic library of Bacillus
      subtilis using an antiserum raised against spore integument, and was sequenced.
      orf2 was 519 nucleotides long and encoded a protein of 172 amino acids with a
      predicted molecular size of 19,552, corresponding to the protein which reacted
      with the antiserum. Immunoelectron microscopic observation indicated that YrbB,
      the product of orf2, was located within the spore integument, mainly in the
      cortex layer with a part in the inner region of the coat layer.

PMID- 9770295
TI  - The CcmE protein from Escherichia coli is a haem-binding protein.
AB  - We previously reported that a 17.5-kDa haem-binding polypeptide accumulates in
      Escherichia coli K-12 mutants defective in an essential gene for cytochrome c
      assembly, ccmF, and speculated that this polypeptide is either CcmE or CcmG. The
      haem-containing polypeptide, which is associated with the cytoplasmic membrane,
      has now been identified by N-terminal sequencing to be CcmE. The haem-dependent
      peroxidase activity of CcmE is clearly visible not only in a ccmF mutant, but
      also in ccmG and ccmH mutants, implying that CcmE functions either before or in
      the same step as CcmF, CcmG and CcmH in cytochrome c maturation. A trxA mutant,
      like the dipZ mutant, was unable to assemble c-type cytochromes or catalyse
      formate-dependent nitrite reduction: both activities were restored in the trxA
      and dipZ, but not ccmG, mutants by the reducing agent, 2-mercaptoethanesulphonic
      acid. Our data suggest that haem transferred across the cytoplasmic membrane by
      the CcmABCD complex becomes associated with CcmE, possibly by a labile covalent
      bond, before it is transferred to the cytochrome c apoproteins by the periplasmic
      haem lyase encoded by ccmF and ccmH. We further propose that CcmG is essential to
      reduce the disulphide bonds formed in cytochrome c apoproteins by DsbA, before
      haem is attached by the haem lyase. Electrons for disulphide bond reduction are
      supplied from thioredoxin in the cytoplasm via DipZ in the membrane, but can be
      replaced by the chemical reductant, 2-mercaptoethanesulphonic acid. According to
      this model, CcmG is the last protein in the reducing pathway which interacts
      stereospecifically with the apoprotein.

PMID- 9770296
TI  - Control of genes by mammalian retroposons.
AB  - Available data on possible genetic impacts of mammalian retroposons are reviewed.
      Most important is the growing number of established examples showing the
      involvement of retroposons in modulation of expression of protein-coding genes
      transcribed by RNA polymerase II (Pol II). Retroposons contain conserved blocks
      of nucleotide sequence for binding of some important Pol II transcription factors
      as well as sequences involved in regulation of stability of mRNA. Moreover, these
      mobile genes provide short regions of sequence homology for illegitimate
      recombinations, leading to diverse genome rearrangements during evolution.
      Therefore, mammalian retroposons representing a significant fraction of noncoding
      DNA cannot be considered at present as junk DNA but as important genetic
      symbionts driving the evolution of regulatory networks controlling gene
      expression.

PMID- 9770297
TI  - Human mitochondrial diseases: answering questions and questioning answers.
AB  - Since the first identification in 1988 of pathogenic mitochondrial DNA (mtDNA)
      mutations, the mitochondrial diseases have emerged as a major clinical entity.
      The most striking feature of these disorders is their marked heterogeneity, which
      extends to their clinical, biochemical, and genetic characteristics. The major
      mitochondrial encephalomyopathies include MELAS (mitochondrial encephalopathy
      with lactic acidosis and stroke-like episodes), MERRF (myoclonic epilepsy with
      ragged red fibers), KSS/CPEO (Kearns-Sayre syndrome/chronic progressive external
      ophthalmoplegia), and NARP/MILS (neuropathy, ataxia, and retinitis
      pigmentosum/maternally inherited Leigh syndrome) and they typically present
      highly variable multisystem defects that usually involve abnormalities of
      skeletal muscle and/or the CNS. The primary emphasis here is to review recent
      investigations of these mitochondrial diseases from the standpoint of how the
      complexities of mitochondrial genetics and biogenesis might determine their
      varied features. In addition, the mitochondrial encephalomyopathies are compared
      and contrasted to Leber hereditary optic neuropathy, a mitochondrial disease in
      which the pathogenic mtDNA mutations produce a more uniform and focal
      neuropathology. All of these disorders involve, at some level, a mitochondrial
      respiratory chain dysfunction. Because mitochondrial genetics differs so
      strikingly from the Mendelian inheritance of chromosomes, recent research on the
      origin and subsequent segregation and transmission of mtDNA mutations is
      reviewed.

PMID- 9770298
TI  - Occludin and the functions of tight junctions.
AB  - The tight junction or zonula occludens is the most apical structure of the
      epithelial junctional complex. Tight junctions from semipermeable intercellular
      diffusion barriers that control paracellular diffusion in a regulated manner.
      This intercellular junction also acts as an intramembrane fence that prevents the
      intermixing of apical and basolateral lipids in the exocytoplasmic leaflet of the
      plasma membrane. Moreover, evidence suggests that tight junction components
      participate in the regulation of cell growth and differentiation. Occludin was
      the first identified transmembrane protein of this intercellular junction and
      received much attention since its molecular characterization. This review
      discusses experiments that were done with occludin and how they influenced our
      current thinking of the molecular functioning of tight junctions.

PMID- 9770299
TI  - Pattern formation and cell differentiation: trichomes in Arabidopsis as a genetic
      model system.
AB  - Arabidopsis trichomes are single-celled hairs that originate from epidermal cells
      and are distributed regularly on most aerial body parts. During the last decade,
      trichome formation in Arabidopsis has been established as a genetic and molecular
      model system to study various general developmental and cellular mechanisms. This
      review summarizes progress in the investigation of several aspects of trichome
      development: the spatial regulation of cell fate determination, the regulation of
      cell differentiation in response to exogenous signals and plant hormones, and the
      regulation of endoreplication, cell growth, and cell morphogenesis.

PMID- 9770300
TI  - The armadillo family of structural proteins.
AB  - The armadillo gene is a segment polarity gene of Drosophila involved in signal
      transduction through wingless. Since the mid-1980s, a growing number of related
      proteins have been identified based on sequence homologies. These proteins share
      a central domain that is composed of a series of imperfect 45 amino acid repeats.
      Armadillo family members reveal diverse cellular locations reflecting their
      diverse functions. A single protein exerts several functions through interactions
      of its armadillo repeat domain with diverse binding partners. The proteins
      combine structural roles as cell-contact and cytoskeleton-associated proteins and
      signaling functions by generating and transducing signals affecting gene
      expression. The study of armadillo family members has made it increasingly clear
      that a distinction between structural proteins on the one hand and signaling
      molecules on the other is rather artificial. Instead armadillo family members
      exert both functions by interacting with a number of distinct cellular-binding
      partners.

PMID- 9770302
TI  - Nature and role of proteasomes in maturation of fish oocytes.
AB  - The proteasome is an essential component of the proteolytic pathway in eukaryotic
      cells and is responsible for the degradation of most cellular proteins.
      Proteasomes are sorted into two types, 20S and 26S. The 20S proteasome forms the
      catalytic core of the 26S proteasome. The 26S proteasome is involved in the
      ubiquitin-dependent protein degradation pathway. Cyclins and cdk inhibitors or c
      mos products, proteins critical to the regulation of the cell cycle, are known to
      be degraded by the ubiquitin pathway. Thus the 26S proteasome is thought to be
      involved in the regulation of cell cycle events. This review focuses on advances
      in the study of the biochemical properties and functions of the 20S and 26S
      proteasomes in the fish meiotic cell cycle.

PMID- 9770301
TI  - Hepatocyte growth factor and the kidney: it is not just for the liver.
AB  - Mesenchymal-epithelial interactions are important for many biological processes
      in epithelial organs such as the kidney. Hepatocyte growth factor (HGF) is a
      mesenchymally derived polypeptide cytokine that acts through its tyrosine kinase
      c-met receptor and is an important mediator of these interactions. This article
      reviews data showing the in vitro actions of HGF on renal epithelial cells that
      result in such diverse responses as mitogenesis, motogenesis, and morphogenesis.
      It also examines the in vivo evidence linking HGF and the c-met receptor to
      kidney development, regeneration following injury, and renal disease. Elucidating
      cellular mechanisms underlying the coordinated control of diverse HGF-induced
      phenotypic changes in renal epithelia in vitro should contribute to a clearer
      understanding of complex biological processes such as organogenesis,
      regeneration, and carcinogenesis in epithelial organs such as the kidney.

PMID- 9770303
TI  - Computational chemistry on commodity-type computers.
AB  - A number of inexpensive computers were benchmarked with the ab initio program
      Gaussian 94, using both small standard test jobs and larger density functional
      (DFT) calculations. Several varieties of Pentium (x86) and Alpha CPU based
      systems were tested. Most of them were running under the open source code
      operating system Linux. They were compared with several workstations and
      supercomputers. The most powerful of today's commodity-type processors surpassed
      current supercomputers in speed. The choice of compilers and compilation options
      was often found to have a larger influence on job CPU times than details of the
      hardware. Especially on the x86 type machines, the jobs always ran faster the
      less memory (RAM) they were given. The fastest machine on a per-CPU basis was an
      Alpha/Linux system. For the DFT calculation, it was close to twice as fast as a
      Cray J90 supercomputer.

PMID- 9770304
TI  - Four-dimensional quantitative structure-activity relationship analysis of a
      series of interphenylene 7-oxabicycloheptane oxazole thromboxane A2 receptor
      antagonists.
AB  - A series of 39 (a training set of 29 and a test set of 10) interphenylene 7
      oxabicyclo [2.2.1]heptane oxazole thromboxane A2 (TXA2) receptor antagonists were
      studied using four-dimensional quantitative structure-activity relationship (4D
      QSAR) analysis. Two thousand conformations of each analogue were sampled to
      generate a conformational energy profile (CEP) from a molecular dynamic
      simulation (MDS) of 100,000 trajectory states. Each conformation was placed in a
      grid cell lattice for each of six trial alignments. Cubic grid cell sizes of 1
      and 2 A were considered. The frequency of occupation of each grid cell was
      computed for each of seven types of pharmacophoric group classes of atoms of each
      compound. These grid cell occupancy descriptors (GCODs) were then used as
      independent variables in constructing three-dimensional (3D)-QSAR models after
      data reduction. The types of data reduction included doing no reducing, reduction
      based on individual GCOD correlation with activity, and reduction from minimum
      variance constraints over the GCOD population. The 3D-QSAR models were generated
      and evaluated by a scheme that combines a genetic algorithm (GA) optimization
      with partial least squares (PLS) regression. The 3D-QSAR models were evaluated by
      cross-validation using the leave-one-out technique. The cross-validated
      correlation coefficient, Q2, ranged from 0.27 to 0.86. The models are not from
      chance correlation because a scrambled data set was generated and evaluated (Q2 =
      0.25-0.37). A composite 3D-QSAR model was constructed using the best models
      derived from GCODs of both 1 and 2 A grid cell size lattices. The 3D-QSAR models
      provide detailed 3D pharmacophore requirements in terms of atom types and
      corresponding locations needed for high TXA2 inhibition activity. Specific sites
      in space that should not be occupied by an active inhibitor are also specified.
      The GCOD measures for the compounds in the training set permit reference points
      regarding which pharmacophore sites can provide the largest boosts in inhibition
      activity relative to the existing analogues.

PMID- 9770305
TI  - Optimization of post-column photolysis and electrochemical detection for the
      liquid chromatographic determination of 3-nitro-L-tyrosine.
AB  - A new post-column photolysis technology has been developed based on the use of a
      low pressure, low temperature UV lamp and TiO2 coated knitted reaction coil. As a
      test case the developed technique was used for the determination of 3-nitro-L
      tyrosine by liquid chromatography with electrochemical detection. Different
      photolysis lamps and reactor tubing lengths were evaluated in terms of their
      effect on the separation efficiency and/or photolysis efficiency. A detection
      limit of 0.5 nM (10 fmol) for 3-nitro-L-tyrosine was achieved under optimized
      conditions, with a linear correlation coefficient of R2 = 0.9898 over a
      concentration range of 2-100 microM. Pre-injection photolysis of 3-nitro-L
      tyrosine indicated that dihydroxyphenylalanine is the main photolysis product. In
      general, use of the photoreactor prior to liquid chromatography is an excellent
      method for exploring photodegradation products of an analyte in conjunction with
      the full range of available liquid chromatography detectors.

PMID- 9770306
TI  - On-line coupling of solid-phase extraction to gas chromatography with mass
      spectrometric detection to determine pesticides in water.
AB  - A group of pesticides with different chemical structures was determined in water
      by on-line coupling of solid-phase extraction to gas chromatography with mass
      spectrometric detection through an on-column interface. A 10 mm x 2 mm I.D.
      precolumn packed with PLRP-S was selected for the solid-phase extraction process.
      The parameters affecting the transfer of the analytes from the precolumn to the
      GC system (e.g. flow-rate, temperature and solvent vapor exit time) were
      optimized. An organic modifier was added to the sample before the extraction
      process to avoid adsorption problems. The use of the MS detector under selected
      ion monitoring acquisition enabled the analytes to be quantified at sub microgram
      per-litre levels preconcentrating only 10 ml of sample, and the limits of
      detection (S/N = 3) were between 2 and 20 ng l-1. The method was applied to the
      determination of the pesticides in tap and river water, and molinate was
      determined in Ebro river water.

PMID- 9770307
TI  - Development of a gas chromatography-mass spectrometry method for the analysis of
      aminoglycoside antibiotics using experimental design for the optimisation of the
      derivatisation reactions.
AB  - A packed column GC-electron-capture detection method for the analysis of the
      aminoglycoside antibiotics kanamycin and gentamicin was adapted to capillary GC
      MS. The analytes were derivatised using a two-step procedure involving
      trimethylsilylation of the hydroxyl groups with trimethylsilylimidazole and
      acylation of the amino groups with heptafluorobutyrylimidazole. Electron impact
      mass spectra of the resulting derivatives of kanamycin A and gentamicins C1, C1a
      and C2 are given and interpreted. The derivatisation procedure was optimised
      using experimental design. This chemometrical approach considers main effects as
      well as interactions of the influential parameters, thus conducting a more
      thorough investigation of the method than the common step-by-step approach.
      Optimisation using fractional factorial and Box Behnken Designs produced a
      derivatisation method featuring better yield than previously published methods
      while in many cases requiring less reagents and shorter reaction times.

PMID- 9770308
TI  - Procedure for the determination of retinol and alpha-tocopherol in poultry
      tissues using capillary gas chromatography with solvent venting injection.
AB  - A procedure designed for the determination of retinol (vitamin A) and alpha
      tocopherol (vitamin E) in poultry tissues has been developed. The procedure
      involves lipid extraction, saponification, solid-phase clean-up and capillary gas
      chromatography (cGC). Retinol and alpha-tocopherol were determined separately by
      cGC-flame ionisation detection using a fused-silica open tubular capillary
      column, 30 m x 0.25 mm I.D. coated with 5% phenylmethylsilicone and with a film
      thickness of 0.25 micron. Solvent extraction followed by saponification were
      sufficient to provide a purified extract which was directly analyzed for retinol
      by cGC in the solvent venting mode. However, in order to accurately determine
      alpha-tocopherol by cGC, further purification of the extract by solid-phase
      extraction was necessary. A silica SPE column was used to remove interfering
      cholesterol from the extract. alpha-Tocopherol was analyzed in its derivatized
      form. Absolute and relative recoveries for both vitamins from spiked samples were
      evaluated. Absolute and relative recoveries ranging from 80 to 95% were obtained
      for both compounds. 5 alpha-Cholestane and alpha-tocopheryl acetate were used as
      internal standards. Poultry muscle meat and liver tissue were analyzed for their
      retinol and alpha-tocopherol content and the peaks detected by cGC were confirmed
      by cGC-mass spectrometry.

PMID- 9770309
TI  - Supercritical fluid extraction and off-line clean-up for the analysis of
      organochlorine pesticide residues in garlic.
AB  - An approach using supercritical fluid extraction (SFE) followed by clean-up with
      a AgNO3-loaded Florisil column was utilized for the analysis of four
      organochlorine pesticides (OCPs) in garlic. The organic sulfur extracted by SFE
      from garlic was removed by AgNO3 allowing OCPs to be determined by GC-electron
      capture detection without interferences. All OCPs recoveries ranged from 85.0% to
      110.0% and relative standard deviations were in the range of 3.9-7.2% for spiked
      samples. The described method may be used to analyze OCPs in garlic on a routine
      basis.

PMID- 9770310
TI  - Determination of organonitrogen pesticides in large volumes of surface water by
      liquid-liquid and solid-phase extraction using gas chromatography with nitrogen
      phosphorus detection and liquid chromatography with atmospheric pressure chemical
      ionization mass spectrometry.
AB  - During a recent study to determine the fluxes and fates of contaminants in the
      St. Lawrence River, the majority of organonitrogen pesticides analysed in samples
      of surface water were found in the dissolved phase. This paper compares two
      extraction techniques and two analytical techniques for 10 chemicals
      (metolachlor, seven triazines and two degradation products of atrazine-cyanazine
      propazine and simazine) in the dissolved phase in large volumes of surface water,
      using a fibre glass filter with 0.7 micron porosity. Samples of filtered surface
      water (1-20 l) were extracted by means of a liquid-liquid technique using the
      Goulden large-sample extractor, and by means of a solid-phase extraction
      technique, using cartridges filled with 500 mg of a large particle-size
      graphitized carbon black as adsorbent: Carbopack B (500-666 microns). The
      pesticides were analysed by gas chromatography on two DB-5 and DB-210 capillary
      columns with nitrogen-phosphorus detection (GC-NPD) and by liquid chromatography
      coupled with mass spectrometry equipped with an atmospheric pressure chemical
      ionization interface (LC-APCI-MS). The recoveries were high (67-100%) for the
      majority of the target pesticides in a volume of 17.85 l of Milli-Q water,
      compared to recoveries in the same volume of filtered surface water (51-102%).
      The detection limits ranged from 0.4 to 4 ng/l and from 0.6 to 3 ng/l for GC-NPD
      and LC-ACPI-MS techniques, respectively.

PMID- 9770311
TI  - Determination of linear alkylbenzenesulfonates and their degradation products in
      water samples by gas chromatography with ion-trap mass spectrometry.
AB  - A method was developed for the analysis of linear alkylbenzenesulfonates (LAS)
      and their degradation products, sulfophenylcarboxylic acids (SPC), in samples of
      sewage effluent and river water. This method involved extraction of the samples
      by graphitized carbon black cartridge, esterification by a two-step thionyl
      chloride-trifluoroethanol derivatization procedure, and separation,
      identification and quantitation by ion-trap GC-MS with EI and low pressure CI
      modes. High selectivity with few signals was observed in the low pressure CI mass
      spectra of LAS and SPC. Enhanced sensitivity with protonated molecular ion
      chromatograms of homologous C10-C13 LAS by CI-MS permit the determination of LAS
      and SPC at trace concentrations in environmental samples. Recovery rates of LAS
      and SPC in spiked water samples ranged from 75 to 112% with R.S.D. values from 3
      to 26%. The limit of quantitation for both LAS and SPC was estimated to be 0.01
      microgram/l in 100 ml of water sample.

PMID- 9770312
TI  - Attachment behavior in dogs (Canis familiaris): a new application of Ainsworth's
      (1969) Strange Situation Test.
AB  - Fifty-one owner-dog pairs were observed in a modified version of M. D. S.
      Ainsworth's (1969) Strange Situation Test. The results demonstrate that adult
      dogs (Canis familiaris) show patterns of attachment behavior toward the owner.
      Although there was considerable variability in dogs' attachment behavior to
      humans, the authors did not find any effect of gender, age, living conditions, or
      breed on most of the behavioral variables. The human-dog relationship was
      described by means of a factor analysis in a 3-dimensional factor space: Anxiety,
      Acceptance, and Attachment. A cluster analysis revealed 5 substantially different
      classes of dogs, and dogs could be categorized along the secure-insecure attached
      dimensions of Ainsworth's original test. A dog's relationship to humans is
      analogous to child-parent and chimpanzee-human attachment behavior because the
      observed behavioral phenomena and the classification are similar to those
      described in mother-infant interactions.

PMID- 9770313
TI  - Perception of scent over-marks by golden hamsters (Mesocricetus auratus): novel
      mechanisms for determining which individual's mark is on top.
AB  - Hamsters preferentially remember or value the top scent of a scent over-mark.
      What cues do they use to do this? Using habituation-discrimination techniques, we
      exposed male golden hamsters (Mesocricetus auratus) on 3 to 4 trials to genital
      over-marks from 2 females and then tested subjects for their familiarity with
      these 2 scents compared with that of a novel female's secretion. Preferential
      memory for 1 of the 2 individuals' scents did not occur if the 2 marks did not
      overlap or did not overlap but differed in age, but it did occur if a region of
      overlap existed or 1 mark apparently occluded another (but did not overlap it).
      Thus, hamsters use regions of overlap and the spatial configuration of scents to
      evaluate over-marks. These phenomena constitute evidence for previously
      unsuspected perceptual abilities, including olfactory scene analysis, which is
      analogous to visual and auditory scene analysis.

PMID- 9770314
TI  - Frequency-range discriminations: special and general abilities in zebra finches
      (Taeniopygia guttata) and humans (Homo sapiens).
AB  - The acoustic frequency ranges in birdsongs and human speech can provide important
      pitch cues for recognition. Zebra finches and humans were trained to sort
      contiguous frequencies into 3 or 8 ranges, based on associations between the
      ranges and reward. The 3-range task was conducted separately in 3 spectral
      regions. Zebra finches discriminated 3 ranges in the medium and high spectral
      regions faster than in the low region and discriminated 8 ranges with precision.
      Humans discriminated 3 ranges in all 3 spectral regions to the same modest
      standard and acquired only a crude discrimination of the lowest and highest of 8
      ranges. The results indicate that songbirds have a special sensitivity to the
      pitches in conspecific songs and, relative to humans, have a remarkable general
      ability to sort pitches into ranges.

PMID- 9770315
TI  - Imitation of the sequential structure of actions by chimpanzees (Pan
      troglodytes).
AB  - Imitation was studied experimentally by allowing chimpanzees (Pan troglodytes) to
      observe alternative patterns of actions for opening a specially designed
      "artificial fruit." Like problematic foods primates deal with naturally, with the
      test fruit several defenses had to be removed to gain access to an edible core,
      but the sequential order and method of defense removal could be systematically
      varied. Each subject repeatedly observed 1 of 2 alternative techniques for
      removing each defense and 1 of 2 alternative sequential patterns of defense
      removal. Imitation of sequential organization emerged after repeated cycles of
      demonstration and attempts at opening the fruit. Imitation in chimpanzees may
      thus have some power to produce cultural convergence, counter to the supposition
      that individual learning processes corrupt copied actions. Imitation of
      sequential organization was accompanied by imitation of some aspects of the
      techniques that made up the sequence.

PMID- 9770316
TI  - Seeing through sound: dolphins (Tursiops truncatus) perceive the spatial
      structure of objects through echolocation.
AB  - Experiment 1 tested a dolphin (Tursiops truncatus) for cross-modal recognition of
      25 unique pairings of 8 familiar, complexly shaped objects, using the senses of
      echolocation and vision. Cross-modal recognition was errorless or nearly so for
      24 of the 25 pairings under both visual to echoic matching (V-E) and echoic to
      visual matching (E-V). First-trial recognition occurred for 20 pairings under V-E
      and for 24 under E-V. Echoic decision time under V-E averaged only 1.88 s.
      Experiment 2 tested 4 new pairs of objects for 24 trials of V-E and 24 trials of
      E-V without any prior exposure of these objects. Two pairs yielded performance
      significantly above chance in both V-E and E-V. Also, the dolphin matched
      correctly on 7 of 8 1st trials with these pairs. The results support a capacity
      for direct echoic perception of object shape by this species and demonstrate that
      prior object exposure is not required for spontaneous cross-modal recognition.

PMID- 9770317
TI  - How do octopuses use their arms?
AB  - A taxonomy of the movement patterns of the 8 flexible arms of octopuses is
      constructed. Components consist of movements of the arm itself, the ventral
      suckers and their stalks, as well as the relative position of arms and the skin
      web between them. Within 1 arm, combinations of components result in a variety of
      behaviors. At the level of all arms, 1 group of behaviors is described as
      postures, on the basis of the spread of all arms and the web to make a 2
      dimensional surface whose position differs in the 3rd dimension. Another group of
      arm behaviors is actions, more or less coordinated and involving several to all
      arms. Arm control appears to be based on radial symmetry, relative
      equipotentiality of all arms, relative independence of each arm, and separability
      of components within the arm. The types and coordination of arm behaviors are
      discussed with relationship to biomechanical limits, muscle structures, and
      neuronal programming.

PMID- 9770318
TI  - The assessment of menstrual synchrony: comment on Weller and Weller (1997)
AB  - A. Weller and L. Weller (1997) claimed to report "the definitive study of
      menstrual synchrony" (p. 148). To allow for cycle variability, they used the
      following criterion for synchrony: It occurred in 2 out of 3 months. The
      underlying assumption of the state of menstrual synchrony is that cycle length
      variability is minimal. The present article uses a random selection of cycle
      lengths from a distribution described by R. F. Vollman (1977) to illustrate how
      variable cycle lengths cause a fluctuation from synchrony to a synchrony. A.
      Weller and L. Weller's (1997) study is not, therefore, conclusive, and future
      studies of menstrual synchrony should include an assessment of cycle variability
      as well as onset difference.

PMID- 9770320
TI  - Lead in the ambient air and blood of children in Helsinki.
AB  - Lead concentrations have been measured in the ambient air of Helsinki since 1978.
      The mean air concentrations at various stations reached maximum values in 1980 of
      333-1150 ng/m3. From 1980 to 1996 the concentrations decreased to one-hundredth,
      from 745 to 7 ng/m3, at the two centrally situated stations where measurements
      were made continuously. Concomitantly, the estimated annual emissions of lead in
      Helsinki decreased from 78 tons to < 1 ton, mainly owing to the cessation of lead
      emissions in exhaust gases from road traffic. The reduction in lead levels in the
      ambient air has been reflected by the lead levels in the blood of children in a
      centrally situated day-care centre. The mean concentration of lead in the blood
      of children in the day-care centre was 46 micrograms/l in 1983, 30 micrograms/l
      in 1988 and 26 micrograms/l in 1996.

PMID- 9770321
TI  - Use of home test kits for detection of lead and cadmium in ceramic dinnerware.
AB  - Commercial home test kits are advertised as a convenient means for assessing
      heavy metal hazards in old ceramic dinnerware. This paper reports investigations
      carried out with four commercial kits for detection of lead (Pb) and one for
      detection of cadmium (Cd) on pre-1970s ceramic dishes subsequently subjected to
      24-h leaching tests with 4% acetic acid to determine heavy metal release. With
      the lead kits, fewer than 10% of dishes leaching greater than 3.0 micrograms
      Pb/ml yielded negative results (i.e. false negatives). When the cadmium kit was
      used according to manufacturer's instructions, 29% of dishes leaching greater
      than 0.5 microgram Cd/ml yielded false negatives. Home lead test kits appear to
      be useful for screening of old dinnerware, but the cadmium kit may not be
      suitable for this purpose.

PMID- 9770322
TI  - Adhesion of water-borne particulates on freshwater biota.
AB  - The retention of suspended particles transported by river flow on surfaces of
      freshwater plants is a potentially important process in the contamination of
      aquatic biota. Field experiments have been performed to test the role of benthic
      algae (periphyton) in trapping inorganic suspended solids transported by the
      river water and to discriminate between the caesium content of periphyton caused
      by the adherence of inorganic solids and by the active uptake inside the
      organisms. The contribution of caesium of suspended solids adhering to biotic
      surfaces was estimated by determining the scandium content (scandium method). The
      scandium method was used because this element is geologically ubiquitous in soils
      and it is not taken up actively by plants and other organisms. The mass of
      suspended particles retained on the surfaces of microorganisms growing on
      submerged substrates were determined by comparing the scandium content of
      suspended material with that in algal communities. Neutron activation analysis
      was used as the analytical method for determination for both scandium, and
      caesium. The results indicate that the suspended particle fraction can contribute
      up to 80% of the caesium contamination of periphyton samples. Active caesium
      uptake and accumulation by aquatic biota represents the remaining 20% of the
      total caesium contamination.

PMID- 9770323
TI  - A simple modelling approach for water quality: the example of an estuarine
      impoundment.
AB  - With the increasing development of water quality standards for all forms of water
      bodies and all forms of their uses, there is a greater need for models that can
      predict water quality in relation to these standards. This paper proposes an
      empirical method based on logistic regression techniques that deliver
      probabilities that given quality standards are met (i.e. water above or below the
      given standard). This technique is applied to data from a saline intrusion
      barrage (River Wansbeck, Northumberland, England) to predict low water quality
      events on the basis of UK water standards. The approach accurately classifies the
      overwhelming majority of pollution events that are caused by processes internal
      to the system. Misclassification can be ascribed to external processes, such as
      combined sewer outfalls. The general applicability of this method is compared to
      physically-based models.

PMID- 9770324
TI  - Dioxins and furans in air and deposition: a review of levels, behaviour and
      processes.
AB  - This paper is a comprehensive, critical review of the levels, behaviour and
      processes affecting polychlorinated dibenzo-p-dioxins and -furans (PCDD/Fs) in
      air and deposition. Aspects of sampling, analysis and quality assurance/control
      are discussed initially, before a review of the PCDD/F concentrations in ambient
      air is presented. The general trend in sigma P4-8 CDD/F (and sigma TEQ) is:
      remote sites < 0.5 pg/m3 (sigma TEQ < 10 fg/m3); rural sites approximately 0.5-4
      pg/m3 (sigma TEQ approximately 20-50 fg/m3); and urban/industrial sites
      approximately 10-100 pg/m3 (sigma TEQ approximately 100-400 fg/m3). The commonly
      held view that a consistent mixture of PCDD/Fs in air exists is evaluated and
      questioned. Issues of seasonality and short-term changes in air concentrations
      are also critically discussed, with respect to the possibility of seasonal
      emission sources to air and seasonally dependent loss processes. Data on the gas
      particle partitioning of PCDD/Fs in air are reviewed; the limited database to
      date is believed to provide evidence for an exchangeable transfer of PCDD/Fs
      between these two phases. The potential importance of photolytic and radical
      reaction degradation processes and wet/dry deposition processes in modifying the
      mixture of PCDD/Fs in air is discussed. Some homologue/congener specific
      'weathering' of the mixture of PCDD/Fs emitted to the atmosphere clearly occurs,
      but in general PCDD/Fs have 'long' atmospheric residence times, rendering them
      subject to long-range atmospheric transport. Data are reviewed which relate the
      mixture of PCDD/Fs in air to that in deposition; this leads to the conclusion
      that different homologue groups (which are partitioned differently between the
      gas and particulate phase) are transferred to the earth's surface with broadly
      similar efficiencies.

PMID- 9770325
TI  - Activation of interleukin-1beta-converting enzyme by nigericin is independent of
      apoptosis.
AB  - Interleukin-1beta-converting enzyme (ICE) is believed to be one of the key
      proteases involved in apoptosis. Since the precursor form of interleukin-1beta
      (pre-IL-1beta) is one of the well known substrates for ICE, and a
      potassium/proton ionophore, nigericin, enhances IL-1beta processing, the authors
      hypothesized that nigericin induces apoptosis through the activation of ICE. In a
      lipopolysaccharide (LPS)-stimulated and nigericin-treated human monocytic cell
      line, THP-1, apoptosis was induced, as assessed as to a decrease in cell size,
      chromatin condensation, exposure of phosphatidylserine and DNA fragmentation.
      Under exactly the same conditions, nigericin also induced IL-1beta processing in
      these cells, which was significantly inhibited by an ICE inhibitor, acetyl-Tyr
      Val-Ala-Asp-CHO. On the contrary, treatment with this inhibitor at the same
      concentration did not inhibit nigericin-induced apoptosis, assessed as to the
      decrease in cell size, chromatin condensation and DNA fragmentation. Although
      apoptosis induced by nigericin was also observed for LPS-stimulated human
      peripheral blood mononuclear cells and a mouse T lymphoma cell line, EL-4, the
      ICE inhibitor did not inhibit the apoptosis in the cells. These results suggest
      that activated ICE is not involved in the apoptosis induced by nigericin. Since
      apopain activity was not augmented under the same conditions, neither ICE nor
      apopain may play any role in the nigericin-induced apoptosis.

PMID- 9770326
TI  - Acid sphingomyelinase-derived ceramide is not required for inflammatory cytokine
      signalling in murine macrophages.
AB  - Sphingomyelin hydrolysis is induced in myeloid cell-lines by tumour necrosis
      factor alpha (TNF-alpha), interleukin 1 beta (IL-1beta), and interferon gamma
      (IFN-gamma). Ceramide, a product of sphingomyelin hydrolysis, recapitulates many
      of the cellular responses elicited by these cytokines, and this has lead to the
      hypothesis that ceramide is a second messenger of cytokine signalling.
      Sphingomyelin hydrolysis is catalysed by an acid spingomyelinase (ASMase) and one
      or more neutral sphingomyelinases (NSMase); both ASMase and NSMase are activated
      during cytokine signalling. In the present study, the contribution of ASMase to
      TNF-alpha, IL-1beta, and IFN-gamma signalling in murine macrophages was
      addressed. Cytokine-induced responses were compared in macrophages derived from
      the bone marrow of AMSase null and wild-type mice. Specifically, TNF-alpha-and
      IFN-gamma-induced nitric oxide production and TNF-alpha- and IL-1beta-induced
      expression of the alpha-chemokine, KC, were intact in ASMase null macrophages.
      Furthermore, TNF-alpha induction of p42/p44 ERK and p38-MAPK phosphorylation, c
      jun kinase activation, and IkappaBalpha degradation were normal. Also normal in
      ASMase null macrophages was TNF-alpha-, IL-1beta- and IFN-gamma-induced
      expression of a panel of early response genes. It is concluded that ASMase is non
      essential for the inflammatory signals activated in murine macrophages by TNF
      alpha, IL-1beta and IFN-gamma.

PMID- 9770327
TI  - The role of caspase 3 and BclxL in the action of interleukin 7 (IL-7): a survival
      factor in activated human T cells.
AB  - The effects of interleukin 7 (IL-7) on apoptosis in interleukin 2 (IL-2)
      dependent, activated, primary, human T lymphocytes (hT cells) was examined. IL-7
      (like IL-2) rescued cells from apoptosis, as measured by their cellular DNA
      profile and fragmentation. IL-2 also acted as a mitogen in these T cells. Both
      cytokines abrogated the dexamethasone-induced stimulation of Caspase 3 and
      prevented the cleavage of poly (ADP-ribose) polymerase (PARP), a substrate for
      the Caspase 3. IL-7 upregulated the expression of Bc1xL and counteracted the
      downregulation of this anti-apoptotic protein by the synthetic glucocorticoid,
      dexamethasone. Bcl-2 protein expression was uupregulated by IL-7 with or without
      dexamethasone, but Bc1-2 was expressed at a much lower level than BclxL in these
      cells. Levels of Bax did not markedly change on either cytokine stimulation or
      dexamethasone treatment. An unidentified 23-kDa band, which was recognized by the
      anti-Bc1-2 antibody, was induced by dexamthasone and suppressed by IL-7 and IL-2.
      This protein was subject to independent regulation as compared to the p26 Bc1-2
      protein, suggesting that it may be a novel factor, possibly involved in the
      regulation of apoptosis. A clear role for IL-7 as a survival factor for cytokine
      withdrawal and glucocorticoid induced apoptosis in activated primary hT cells is
      implicated. In addition, regulation of BclxL and downstream inhibition of Caspase
      3 activity may mediate this rescue signal.

PMID- 9770328
TI  - Endothelin 1 receptors, signal transduction and effects on DNA and proteoglycan
      synthesis in rat articular chondrocytes.
AB  - This study showed that endothelins (ETs) stimulate DNA and proteoglycan synthesis
      in monolayer culture of rat articular chondrocytes (AC) by interacting with
      specific cell surface receptors. The high affinity receptors bound [125I]ET-1
      with a Kd of 0.54 nM and Bmax of 81.4 pM/microgram DNA (approximately 40 000
      binding sites per cell) was demonstrated. [125I]ET-1 binding was completely
      inhibited by unlabelled ET-1 or ET-2, and by BQ123 (ETA receptor antagonist),
      whereas ET-3 and IRL1038 (ETB receptor antagonist) did so only weakly. SDS-PAGE
      of cell extracts containing [125I]ET-1 cross-linked to the receptors, followed by
      autoradiography of the gels revealed a single 50-kDa band. These findings
      indicate that most of the receptors are subtype ETA. Although mRNA transcripts
      specific for both ETA and ETB receptors were found by RT-PCR, the ETA mRNA was
      more abundant. ET-1 increased the production of cAMP, cGMP and prostaglandin E2
      (PGE2) and protein kinase C (PKC) activity in a concentration- and time-dependent
      manner. ET-1, and to a lesser degree ET-2, stimulated DNA synthesis, whereas ET-3
      was inactive. Stimulation of DNA synthesis by ET-1 was strongly inhibited in a
      concentration-dependent manner by BQ123 and, to a much lesser degree, by IRL1038,
      which is consistent with an ETA receptor. ET-1 also stimulated proteoglycan
      synthesis and increased the amount of mRNA specific for the aggrecan gene. These
      findings strongly suggest that ET-1 is involved in regulating chondrocyte
      proliferation and metabolism in health, and presumably in disease.

PMID- 9770329
TI  - Regulation by endogenous INTERLEUKIN-10 of the expression of nitric oxide
      synthase induced after ligation of CD23 in human macrophages.
AB  - The possible role of interleukin 10 (IL-10) as an endogenous inhibitor of CD23
      driven inducible nitric oxide synthase (iNOS) expression in human macrophages was
      investigated. Cross-linking of CD23 by a monoclonal antibody induced iNOS mRNA,
      as detected by RT-PCR, and the production of NO measured as the stable
      derivative, nitrite. A linear correlation was observed between CD23 expression
      and iNOS activity or NO2- production. The iNOS activity reached a maximum 48 h
      after ligation of CD23, then declined rapidly until 72 h. In parallel, nitrite
      production was detected after 24 h and reached a maximum after 48 h. In addition,
      ligation of the CD23 molecule induced, in a time-dependent manner, the production
      of IL-10. As this cytokine is known to regulate iNOS induction and activity, we
      evaluated the effect of a neutralizing mAb to IL-10 on CD23-induced iNOS activity
      and nitrite production by CD23-bearing macrophages and found that both were
      significantly enhanced. Furthermore, the addition of exogenous IL-10 suppressed
      CD23-driven iNOS mRNA expression, iNOS activity and production of nitrite. These
      data suggest that, after CD23-ligation at the cell surface of human phagocytes,
      the secretion of IL-10 downregulates the CD23-induced NO production at the
      transcriptional level, thus providing an efficient feed-back mechanism.

PMID- 9770331
TI  - Spontaneous secretion of interleukin 1 receptor antagonist (IL-1ra) by cells
      isolated from herniated lumbar discal tissue after discectomy.
AB  - In the study presented, cells of a herniated lumbar disc were cultivated in vitro
      and analysed for interleukin 1beta (IL-1beta) and interleukin 1 receptor
      antagonist (IL-1Ra) production. The objective of this study was the detection of
      IL-1beta and IL-1Ra secreted by herniated lumbar discal cells after discectomy.
      The involvement of cytokines in the degeneration of intervertebral discs and in
      the pathophysiology of radiculopathy is established. Antagonizing proteins, e.g.
      IL-1Ra are thought to have considerable therapeutic potential. In the present
      study, a 51-year-old male with massive sequestrated lumbar disc herniation at
      L5/S1 was treated by microsurgical discectomy. Discal cells were isolated,
      cultures and culture supernatants immunochemically analysed for IL-1beta and IL
      1Ra secretion. Spontaneous secretion of IL-1Ra was found. IL-1beta was not
      detected. Our findings might contradict recent studies on the role of IL-1beta
      and IL-1Ra. A possible therapeutic role of exogenous IL-1Ra in disc degeneration
      needs further research.

PMID- 9770330
TI  - Different roles of tumour necrosis factor alpha and interleukin 1 in murine
      streptococcal cell wall arthritis.
AB  - In this study two different aspects of tumour necrosis factor alpha (TNF-alpha)
      and interleukin 1 (IL-1) in locally induced murine streptococcal cell wall
      arthritis (SCW) were investigated. First, the kinetics and interdependence of TNF
      alpha and IL-1 release; and second; their involvement in inflammation and
      cartilage destruction. Kinetic studies showed that the TNF-alpha peak level
      preceded the IL-1 peak level. However, in vivo neutralization of TNF-alpha did
      not result in decreased IL-1 bioactivity or immunoreactivity, suggesting that
      there is no dominant TNF-alpha-dependent IL-1 release in this model. Inflammation
      was studied by measuring knee joint swelling and inflammatory cell influx. Impact
      on cartilage was studied by measuring chondrocyte proteoglycan synthesis and
      cartilage proteoglycan depletion. The role of TNF-alpha in these phenomena was
      investigated using anti-TNF-alpha antibodies and tumour necrosis factor binding
      protein (TNFbp). Similarly, the role of IL-1 was studied using anti-IL-1
      antibodies or IL-1 receptor antagonist (IL-1Ra). Anti-TNF-alpha treatment
      significantly reduced joint swelling, whereas this effect was not found by using
      anti-IL-1 or IL-1Ra. In contrast, neutralization of IL-1, but not TNF-alpha,
      resulted in a significant decrease of chondrocyte proteoglycan synthesis
      inhibition. Moreover, histology revealed that anti-IL-1 treatment reduced
      cartilage proteoglycan depletion and inflammatory cell influx. Combined anti-TNF
      alpha/anti-IL-1 treatment significantly suppressed both inflammation and
      cartilage damage. However, the impact on these separate parameters did not exceed
      the effects of either anti-TNF-alpha or anti-TNF-1. It can be concluded that both
      TNF-alpha and IL-1 exert specific activities in SCW arthritis. The involvement of
      TNF-alpha in this model is limited to joint swelling, whereas IL-1 plays a
      dominant role in cartilage destruction and inflammatory cell influx.

PMID- 9770332
TI  - Early modifications of chemokine production and mRNA expression during rush venom
      immunotherapy.
AB  - The mechanism by which specific immunotherapy exerts its beneficial effect
      remains unclear. Chemokines are implicated in inflammatory and allergic diseases,
      in particular via their ability to induce histamine release from basophils, a
      potential early target of rush venom immunotherapy (RVIT), In this study, the
      authors evaluated ex vivo regulated upon activation normal T-cell expressed and
      secreted (RANTES), interleukin 8 (IL-8) and monocyte chemoattractant protein 1
      (MCP-1) production and mRNA expression by mononuclear cells (MNC) from nine
      patients undergoing a 3.5-h ultra rush treatment, before treatment at Day 0 (D0),
      at the end of the 3.5-h of the rush at Day 4h (D4h), at Day 15 (D15) and Day 45
      (D45) after treatment. Increased RANTES release and mRNA expression were observed
      in 24-h culture of peripheral blood MNC collected at D4h. This was followed by a
      decrease in the production of RANTES, IL-8 and MCP-1, 45 days after initiation of
      RVIT. The same pattern was observed after in vitro venom stimulation of MNC. At
      the mRNA level, similar profiles were observed except for IL-8 mRNA which
      inversely increased during RVIT. These results suggest that RVIT is associated
      with a general decrease in chemokines which may explain, in part, the clinical
      efficacy of specific immunotherapy.

PMID- 9770333
TI  - Immunolocalization of cytokines and growth factors in oral submucous fibrosis.
AB  - Oral submucous fibrosis (OSF) is a chronic fibrotic disease of the oral cavity
      and oropharynx characterized by fibroelastic change in the mucosa which leads to
      progressive inability to open the mouth. The inflammatory cells in the lesional
      tissue consist mainly of T lymphocytes, with a high CD4:CD8 ratio, and major
      histocompatibility complex (MHC) class II expressing antigen-presenting cells.
      Cytokines and growth factors produced by inflammatory cells within the lesion may
      promote fibrosis by inducing proliferation of fibroblasts, upregulating collagen
      synthesis and downregulating collagenase production. The authors used a three
      stage immunoperoxidase technique to investigate the expression of interleukin
      alpha (IL-1alpha) and beta, IL-6 interferon (IFN)-alpha, beta and gamma,
      transforming growth factor beta (TGF-beta), platelet-derived growth factor (PDGF)
      and basic fibroblast growth factor (bFGF) in frozen sections of OSF and compared
      it with that in normal buccal mucosa. The expression of cytokines and growth
      factors in normal tissues was consistent with their well known distribution and
      cell of origin, but the intensity and distribution in OSF were all, with the
      exception of IFN-alpha and gamma, upregulated with strong expression in both the
      epithelium and underlying connective tissue. IFN-alpha showed a similar pattern
      of staining in both normal mucosa and OSF. IFN-gamma showed little or no
      expression in most lesional tissues, suggesting an innate deficiency or
      downregulation of this cytokine. The general increase in pro-inflammatory
      cytokines and growth factors, and reduced production of IFN-gamma, may play an
      important role in the pathogenesis of OSF.

PMID- 9770334
TI  - The effects of IL-6 on cell adhesion and e-cadherin expression in breast cancer.
AB  - Interleukin 6 (IL-6) is a pleiotropic inflammatory cytokine and its role in
      cancer is not yet clear. The effects of IL-6 on four breast cancer cell lines and
      normal mammary epithelium, cultured from milk were tested. Four different
      patterns of response to IL-6 were found depending on the differentiation status
      of the cells. In normal mammary epithelial cultures, the effects of IL-6 were
      mainly growth inhibitory, whereas in MCF-7, IL-6 had growth inhibitory and anti
      adhesive effects. In T-47D and ZR-75-1 the anti-adhesive effects were prominent
      although the growth inhibitory effects were not. These anti-adhesive effects were
      associated with epithelioid to fibroblastoid morphological changes and a local
      decrease in E-cadherin expression. In the highly invasive cell line MDA-MB-231,
      which does not express E-cadherin, no effects of IL-6 were seen. IL-6 levels in
      the serum of 60 breast cancer patients were found to be increased in 27% (16/60)
      compared to 2% (1/50) in a control group. Furthermore, it was found that altered
      E-cadherin expression was seen in 69% of the primary tumours, although no
      significant association was found between raised serum IL-6 levels and altered E
      cadherin expression. Finally IL-6 serum levels did not effect the survival of
      breast cancer patients. The authors therefore implicate IL-6 as a possible factor
      important in breast cancer progression and metastasis formation, although the
      clinical significance of this cytokine in breast cancer patients could not be
      established.

PMID- 9770335
TI  - A possible role for soluble IL-6 receptor in the pathogenesis of systemic onset
      juvenile chronic arthritis.
AB  - Investigation of the agonist and two antagonists to interleukin 6 (IL-6) and
      their possible role in the pathogenesis of different sub-groups of juvenile
      chronic arthritis (JCA). Sera of 54 patients and 10 age-matched controls were
      tested: 20 with pauci-articular JCA, 12 with polyarticular JCA, and 22 systemic
      JCA. Interleukin 6, soluble interleukin 6 receptor (agonist), soluble gp130 and
      autoantibodies to IL-6 (antagonist to IL-6) were measured, as well as C-reactive
      protein as an indicator of disease activity. In addition, during fever two
      systemic JCA patients were analysed longitudinally for these parameters. There
      was a significant increase in soluble IL-6 receptor (sIL-6R) concentrations. No
      difference in the levels of soluble gp130 and autoantibodies to IL-6 in the
      systemic JCA group was found. In two patients the fever curves corresponded to
      the IL-6 levels measured. sIL-6R serum concentrations also showed a tendency to
      follow the fever. The authors have shown that in systemic JCA, the levels of sIL
      6R, agonist of IL-6, were increased significantly compared to the other groups,
      while levels of antagonists to IL-6 were not changed in the face of increased
      levels of IL-6 in systemic JCA. These results suggest an imbalance of IL-6
      homeostasis.

PMID- 9770336
TI  - Neuregulins and erbB receptors at neuromuscular junctions and at agrin-induced
      postsynaptic-like apparatus in skeletal muscle.
AB  - We demonstrate by immunohistochemistry that at least two isoforms of neuregulin
      (NRG) are concentrated at neuromuscular junctions in adult rat muscles. One is
      NRGbeta3, a secreted protein which is bound to basal lamina that occupies the
      synaptic cleft. The other(s), NRG-a, is in the muscle fibers' plasma membrane. We
      show further that muscle NRG, including NRG-a, is concentrated at postsynaptic
      like apparatus induced to form in the extrajunctional region of the soleus muscle
      by exposure to neural agrin. The agrin-induced postsynaptic-like apparatus also
      includes aggregates of the NRG receptors erbB2 and erbB3 as does postsynaptic
      apparatus at neuromuscular junctions. These findings together with those of
      others suggest a mechanism by which neural agrin induces the expression of
      epsilon-AChR subunits in postsynaptic-like apparatus, and they support the
      hypothesis that agrin has a similar function at neuromuscular junctions.

PMID- 9770337
TI  - The transcription factor E2F-1 in SV40 T antigen-induced cerebellar Purkinje cell
      degeneration.
AB  - Transgenic targeting of SV40 large T antigen (Tag) expression to murine
      cerebellar Purkinje cells induces these normally postmitotic neurons to undergo
      DNA synthesis and apoptosis. It has been proposed that these effects of Tag are
      due to the binding of Tag to pRb, which leads to the release and activation of
      the transcription factor E2F. Here it is reported that E2F and CDC2, the protein
      product of a gene regulated by E2F, were detectable in the Purkinje cell nuclei
      of Tag expressing transgenic animals. To directly test whether E2F-1 is part of
      the mechanism of Tag-induced Purkinje cell degeneration, transgenic mice that
      overexpress E2F-1 specifically in cerebellar Purkinje cells were generated.
      Although E2F-1 itself did not affect Purkinje cells, it did accelerate Tag
      induced ataxia and Purkinje cell loss, suggesting that E2F-1 can contribute to
      the mechanism of Tag-induced Purkinje cell degeneration.

PMID- 9770338
TI  - A novel phosphatase regulating neurite extension on CNS inhibitors.
AB  - The inability of injured axons to regenerate in the adult mammalian central
      nervous system is thought to be in part due to inhibitory molecules synthesized
      by oligodendrocytes and present in myelin. We describe the cloning of a cDNA
      encoding a novel neuronal protein, named NERPP-2C, which is distantly related to
      protein phosphatase 2C and plays a role in the inhibitory response pathway to
      myelin inhibitors. NERPP-2C is expressed in neuronal cell lines and in rat brain.
      Expression in rat is detectable at E15, increases with age, and is highest in
      adulthood. Exposure of NG108-15 cells to antisense oligonucleotides reduces NERPP
      2C expression and overcomes the inhibition of neurite extension on CNS myelin
      substrates in vitro. Antibodies to NERPP-2C detect two proteins, approximately 55
      and 80 kDa in size, the smaller of which is found in the cytoplasm, and the
      larger is associated with the membrane fraction. The antibodies specifically
      immunoprecipitate a protein which exhibits serine/threonine and tyrosine
      phosphatase activity. NERPP-2C is localized in neurites and in growth cones, as
      well as in the cell nucleus. We hypothesize that NERPP-2C is a component in the
      signal transduction pathway for neuronal growth inhibitory factors in CNS myelin.

PMID- 9770339
TI  - Role of L1 in neural development: what the knockouts tell us.
AB  - Mutations in the cell adhesion molecule L1 cause severe developmental anomalies
      in the human nervous system. Recent descriptions of L1 gene knock-out mice from
      three research groups demonstrate that these mice are strikingly similar to
      humans with mutations in the L1 gene. In both humans and mice there are defects
      in the development of the corticospinal tract and cerebellar vermis,
      hydrocephalus, and impaired learning. The production of a viable animal model for
      X-linked hydrocephalus suggests that unanswerable questions posed by the human
      disease will finally be approachable using modern experimental methods.

PMID- 9770340
TI  - Developmental changes of agonist affinity at GABABR1 receptor variants in rat
      brain.
AB  - Recently, two N-terminal splice variants of the metabotropic receptor for GABA
      (gamma-amino-butyric acid) were cloned. Here, we describe an antiserum that
      recognizes the two receptor variants. We demonstrate that these proteins are
      identical with GABAB receptors that are photoaffinity labeled with [125I]CGP71872
      in rat brain. The C-terminal epitopes recognized by the antiserum are conserved
      in several vertebrate species but not in chicken. No hints for the existence of
      additional closely related receptor subtypes or variants are found in double
      labeling experiments with antibody and photoaffinity ligand. Western blot
      analysis reveals widespread expression of the GABABR1 receptor proteins in rat
      brain with the highest level of expression at early postnatal stages. The binding
      affinity of the GABAB receptor agonist L-baclofen at native R1a and R1b variants
      is similar. In early postnatal development the affinity at R1a and R1b is 10-fold
      lower than in adult brain and gradually increases with aging.

PMID- 9770341
TI  - A novel strategy for introducing exogenous bcl-2 into neuronal cells: the
      Cre/loxP system-mediated activation of bcl-2 for preventing programmed cell death
      using recombinant adenoviruses.
AB  - We have established a novel strategy for introducing exogenous Bcl-2 into
      neuronal cells that is mediated by Cre/loxP recombination using recombinant
      adenoviral vectors. An on/off-switching cassette for Bcl-2 (CALNLbcl-2) was
      designed to express Bcl-2 by recombinase Cre-mediated excisional deletion of a
      spacer DNA flanked by a pair of loxP sites. Exogenous Bcl-2 was clearly induced
      in PC12 cell lines carrying CALNLbcl-2 after infection with recombinant
      adenovirus producing recombinase Cre (AxCANCre). Dual infection with both
      AxCANCre and a recombinant adenovirus bearing CALNLbcl-2 showed efficient
      delivery of exogenous Bcl-2 into a hybrid motoneuronal cell line and primary
      chicken spinal motoneurons. The delivery of foreign Bcl-2 promoted survival of
      motoneurons in medium either containing or lacking trophic support. Thus, this
      strategy for delivery of exogenous Bcl-2 will be useful for studying neuronal
      death as well as for introducing foreign genes into postmitotic neurons under the
      control of recombinase Cre.

PMID- 9770342
TI  - Myelin-associated glycoprotein in myelin and expressed by Schwann cells inhibits
      axonal regeneration and branching.
AB  - The mammalian CNS does not regenerate after injury due largely to myelin-specific
      inhibitors of axonal growth. The PNS, however, does regenerate once myelin is
      cleared and myelin proteins are down-regulated by Schwann cells. Myelin
      associated glycoprotein (MAG), a sialic acid binding protein, is a potent
      inhibitor of neurite outgrowth when presented to neurons in culture. Here, we
      present additional evidence that strongly supports the suggestion that MAG
      contributes to the overall inhibitory properties of myelin. When myelin from MAG
      /- mice is used as a substrate, axonal length is 100 and 60% longer for neonatal
      cerebellar and older DRG neurons, respectively, compared to MAG+/+ myelin. The
      converse is true for neurites from neonatal DRG neurons, which are twice as long
      on MAG+/+ relative to MAG-/- myelin, consistent with MAG's dual role of promoting
      axonal growth from neonatal DRG neurons but inhibiting growth in older DRG and
      all other postnatal neurons examined. Furthermore, desialylating neurons reverses
      inhibition by CNS myelin by 45%. Contrary to previous reports, under these
      conditions PNS myelin is also inhibitory for axonal regeneration. Importantly,
      results using PNS MAG-/- myelin as a substrate suggest that MAG contributes to
      this inhibition. Finally, when Schwann cells not expressing MAG and permissive
      for axonal growth are induced to express MAG by retroviral infection, not only is
      axonal outgrowth greatly inhibited by these cells but so also is neurite
      branching. This suggests for the first time that MAG not only affects axonal
      regeneration but may also play a role in the control of axonal sprouting.

PMID- 9770343
TI  - Apoptosis may be either suppressed or enhanced with strategic combinations of
      antineoplastic drugs or anti-IgM.
AB  - A variety of drugs have been used to treat B-lymphocyte neoplasms, including both
      cell cycle-specific (CCS) and non-cell-cycle-specific drugs. Although the therapy
      for such cancers is complex and can include both types of drugs, the efficacy of
      these drugs in inducing cell death remains unclear. In this paper we have
      concentrated on specific CCS drugs and have examined their ability to induce
      programmed cell death (apoptosis) in Burkitt's lymphoma cell lines derived from
      patients. The CCS drugs chosen were hydroxyurea and aphidicolin (active in late
      G1, early S phase), the topoisomerase poisons camptothecin and etoposide (S,
      early G2 phase) and vincristine and Taxol (late G2, M phase). These choices allow
      comparison of two drugs with differing modes of action for each of the various
      phases of the cell cycle. Our results indicate that the variation in apoptosis
      between drugs that act at the same phase of the cell cycle is negligible. Both
      S/G2 and G2/M blockers are very potent at inducing apoptosis whereas G1/S
      blockers are ineffective in the induction of apoptosis. In addition, marked
      kinetic variations in the rate of apoptosis induction were observed, etoposide
      and camptothecin being more rapid in their action than the other agents. The
      order of effectiveness in inducing apoptosis on a kinetic basis was S/G2 agents
      >> G2/M agents >> G1/S agents. In this study we have also found that growth
      inhibition was induced by all the CCS agents chosen and by anti-IgM in various
      Burkitt's lymphoma lines. Furthermore c-myc was down-regulated under similar
      conditions. Since apoptosis was only selectively induced by some of the CCS
      agents, it implies c-myc expression is associated with growth regulation and c
      myc down-regulation is an insufficient condition for the induction of apoptosis.
      In addition, cotreatments using the CCS and other agents revealed the following:
      Cotreatment using two CCS drugs which act at the same stage in the cell cycle
      showed either no change or only additivity to the effects seen with either agent
      alone. However, cotreatment with CCS drugs showed that an inhibitory effect is
      found between G1/S and G2/M drugs or S/G2 and G2/M drugs. No effect was found
      between G1/S and S/G2 drugs. Anti-IgM, which by itself was capable of inducing
      apoptosis, was observed to augment apoptosis induced by very low concentrations
      of G2/M-acting drugs but it has little effect on G1/S or the S/G2 drugs. The
      inhibitory effect of anti-CD40 or TNF-alpha on anti-IgM-induced apoptosis did not
      carry over to an effect on apoptosis induction by the CCS agents. Thus specific
      combinations of agents may lead to either enhancement, inhibition, or no
      interactive effect on apoptosis.

PMID- 9770344
TI  - Human cervical cancer-associated nuclear matrix proteins.
AB  - The nuclear matrix is the nonchromatin protein structural component of the
      nucleus that governs nuclear shape and also exerts regulatory control over higher
      order gene organization. Recent studies have documented the presence of tumor
      associated nuclear matrix proteins in several human cancers. We used high
      resolution two-dimensional gel electrophoresis to compare nuclear matrix protein
      patterns in cervical carcinomas with those from normal cervical tissue. Tumors
      obtained from 20 patients undergoing hysterectomy for clinically localized
      cervical cancer were compared with normal cervical tissue. We have identified
      five polypeptides (CvC-1: Mr = 69,408 Da, pI = 5. 78; CvC-2: Mr = 53,752 Da, pI =
      5.54; CvC-3: Mr = 47,887 Da, pI = 5. 60; CvC-4: Mr = 46,006 Da, pI = 5.07; and
      CvC-5: Mr = 44,864 Da, pI = 6.61) in the nuclear matrix from cervical carcinomas
      that were present in 20 of 20 cervical tumors but 0 of 10 normal tissues. These
      data extend similar findings of cancer-associated nuclear matrix proteins in
      other human cancers and suggest that nuclear matrix proteins may represent a new
      class of cancer markers that could aid the diagnosis or management of some types
      of cancer.

PMID- 9770346
TI  - Cellular senescence in telomerase-expressing Syrian hamster embryo cells.
AB  - We have observed that normal, diploid Syrian hamster embryo cells (SHE) express
      the enzyme telomerase but undergo senescence at the end of their replicative
      lifespan. After 20-30 population doublings (pd) these cells cease proliferating,
      enlarge in size, exhibit a pH 6.0 senescence-associated beta-galactosidase
      activity, and fail to phosphorylate the RB protein or enter into S-phase after
      serum stimulation. We have observed that SHE cells express telomerase throughout
      their replicative lifespan and that the average telomere length does not appear
      to decrease, remaining at about 23 kb in senescent cells. In addition, individual
      clones of SHE cells also have telomerase activity and telomeres that do not
      decrease in length, ruling out the possibility that there is a rare, immortal
      subpopulation of telomerase-expressing cells that is lost during passaging.
      Together, these data suggest that SHE cells are likely to senesce by a mechanism
      that does not involve telomere loss.

PMID- 9770345
TI  - Characterization of PKCI and comparative studies with FHIT, related members of
      the HIT protein family.
AB  - We previously described the isolation of a human cDNA that encodes a protein
      termed protein kinase C inhibitor (hPKCI). We elucidated the three-dimensional
      structure of this protein and demonstrated that in vitro, it enzymatically
      hydrolyzes adenosine polyphosphates. To identify other proteins that interact
      with hPKCI, in the present study, we used the hPKCI as a bait in the yeast two
      hybrid system, together with a mouse embryo cDNA library. This led to the
      isolation of a murine PKCI homologue (mPKCI). This finding is consistent with our
      previous structural studies indicating that hPKCI exists as a homodimer and
      indicates the strong conservation of the PKCI sequence during evolution. Northern
      blot analysis indicated that a 0.7-kb PKCI mRNA was expressed in several tissues
      obtained from adult mice and also in a variety of rodent and human cell lines.
      Western blot analyses, using a polyclonal antibody prepared against hPKCI,
      indicated that this protein is expressed at relatively high levels in several
      murine tissues and in a variety of human cell lines prepared from normal tissues
      or tumors. In contrast to these findings, parallel studies with a polyclonal
      antibody to FHIT, a related histidine triad (HIT) protein and putative tumor
      suppressor, indicated that FHIT was expressed at low or undetectable levels in
      some of the same cell lines. Microscopy of immunostained cells indicated that the
      PKCI protein was present mainly in the nucleus of both normal and tumor-derived
      epithelial cell lines. Evidence presented in this and previous studies suggest
      that in vivo the ubiquitously expressed PKCI protein does not function as an
      inhibitor of PKC but rather acts as an enzyme in a yet to be identified pathway.

PMID- 9770347
TI  - Evasion of UVC-induced apoptosis by photorepair of cyclobutane pyrimidine dimers.
AB  - Cyclobutyl pyrimidine dimer (CPD) photolyase is known to reverse pyrimidine
      dimers specifically under illumination with visible light. OCP13, a Medaka cell
      line showing a high level expression of the gene for CPD photolyase, completely
      reversed pyrimidine dimers induced by 20 J/m2 UVC by 1 h of photorepair. When
      OCP13 cells were irradiated with 20 J/m2 UVC, morphological changes such as
      shrinkage of cells, distorted nuclear shape, and decrease in the number of
      nucleoli appeared 2 to 4 h after UVC irradiation. Thereafter, the irradiated
      cells began to detach from the substratum, and DNA ladders were observed in the
      DNA extracted from detached cells. Thus, these changes in cells after UVC
      exposure were used to characterize the progression of UV-induced apoptosis in
      OCP13 cells. Although formation of DNA ladders and cell detachment were blocked
      by cycloheximide treatment prior to UVC exposure, the morphological changes were
      not. With photorepair treatment, even after the morphological changes appeared
      cells were still able to restore their normal morphological features and remained
      attached. On the other hand, the cell-cycle progression in UVC-irradiated cells
      was arrested even after photorepair of pyrimidine dimers. Thus, photorepair can
      rescue cells from UV-induced apoptosis, although DNA damage other than that of
      pyrimidine dimers, as well as additional non-DNA damage, possibly remained, and
      DNA replication was left inhibited. Among the various kinds of damage induced by
      UVC irradiation, the presence of pyrimidine dimers is proposed to be the major
      trigger for UVC-induced apoptosis.

PMID- 9770348
TI  - Inhibitors of transcription, proteasome inhibitors, and DNA-damaging drugs
      differentially affect feedback of p53 degradation.
AB  - Mutations of the p53 gene are the most common abnormalities in human cancer. In
      contrast to mutant p53, wild-type (wt) p53 protein is present at low levels due
      to rapid degradation by proteasome. We demonstrated that wt p53 protein
      stabilization following DNA damage or proteasome inhibition did not abolish the
      wild-type conformation. DNA damage did not cause accumulation of ubiquitinated
      forms of wt p53, suggesting abrogation of ubiquitination. Consistent with this,
      the E6 oncoprotein which targets p53 for ubiquitination abolished stabilization
      of p53 protein by DNA-damaging drugs but not by proteasome inhibitors. In
      contrast to the effects on wt p53, inhibitors of proteolysis downregulated mutant
      p53. Regulation of p53 levels can be explained by a feedback mechanism where wt
      p53 transcriptionally induces "sensor" proteins (Mdm-2, as an example) and these,
      in turn, target p53 for degradation. Like p53, Mdm-2 is degraded by proteasome.
      Therefore, inhibition of proteasome caused accumulation of Mdm-2, leading to
      degradation of mutant p53 by the remaining proteolytic activity of the cell. We
      propose that inhibition of transcription should increase wt p53 protein due to
      inhibition of Mdm-2 synthesis. An inhibitor of transcription, alpha-amanitin,
      dramatically induced wt p53 protein, whereas Mdm-2 protein was downregulated.
      Moreover, alpha-amanitin increased p53 protein levels in E6-transfected cells.
      Although inhibitors of transcription, such as actinomycin D, also damage DNA,
      reduction of Mdm-2 or other putative "sensor" proteins may contribute to their
      p53-stabilizing activity. Similarly, antimetabolites augment accumulation of wt
      p53 due to interference with RNA synthesis.

PMID- 9770349
TI  - Modulation by interleukin-2 of cellular response to fibroblast growth factor-1 in
      F69-3 fibrosarcoma cells.
AB  - FGF-1 stimulated DNA synthesis and induced expression of IL-2 receptors in the
      murine fibrosarcoma cell line, F69-3. Concomitant treatment with IL-2 abolished
      the stimulation of DNA synthesis, but not binding of FGF-1 to the FGF-receptors
      or subsequent endocytosis of the bound growth factor. Also, it did not inhibit
      activation of the FGF-receptor tyrosine kinase or stimulation of the downstream
      effector, MAP kinase. Treatment with IL-2 prevented transport of FGF-1 to the
      nuclear fraction in a time- and dose-dependent manner that parallelled the
      inhibition of FGF-1 stimulated DNA synthesis. The data support our earlier
      finding that transport of FGF-1 to the nucleus is an important event in the
      mechanism of stimulation of DNA synthesis induced by the growth factor, and they
      demonstrate that treatment with a cytokine can modulate the cellular response to
      FGF-1.

PMID- 9770350
TI  - 24R,25-dihydroxyvitamin D3 increases cyclic GMP contents, leading to an
      enhancement of osteocalcin synthesis by 1,25-dihydroxyvitamin D3 in cultured
      human osteoblastic cells.
AB  - The effect of the physiological vitamin D metabolite 24R, 25-dihydroxyvitamin D3
      [24R,25(OH)2D3] on human osteoblastic cells was assessed. Physiological
      concentrations (10(-9)-10(-8) M) of 24R, 25(OH)2D3 significantly increased the
      cyclic guanosine 5'-monophosphate (cGMP) content in the human osteoblastic cells
      by approximately 200% in 5 to 15 min. In contrast, 24S, 25-dihydroxyvitamin D3
      had only a weak effect on the cGMP content, and 1,25-dihydroxyvitamin D3
      [1,25(OH)2D3] did not affect the content. The production of osteocalcin was not
      induced by 10(-9)-10(-8) M of 24R,25(OH)2D3 in the absence of 1,25(OH)2D3.
      However, the same concentration of 24R,25(OH)2D3 showed stimulatory effects on
      osteocalcin synthesis in the presence of 10(-9) M 1, 25(OH)2D3. Rp-8Br-cyclic
      GMP, a specific inhibitor of cyclic GMP-dependent protein kinase, significantly
      inhibited the cooperative effect of 24R,25(OH)2D3 with 1,25(OH)2D3 on the
      osteocalcin synthesis, although Rp-8Br-cyclic AMP, a specific inhibitor of cyclic
      AMP-dependent protein kinase, did not affect the cooperative effect. In addition,
      okadaic acid enhanced the osteocalcin synthesis induced by 1,25(OH)2D3. These
      observations suggest that 24R,25(OH)2D3 has a unique activity of increasing cGMP
      contents in osteoblastic cells, and that the increase in cGMP contents may lead
      to the cooperative effect of 24R,25(OH)2D3 with 1, 25(OH)2D3 on osteocalcin
      synthesis. These data support the hypothesis that 24R,25(OH)2D3 has a
      physiological role in human bone and mineral metabolism.

PMID- 9770351
TI  - DNA content and chromatin texture of benzo[a]pyrene-transformed human breast
      epithelial cells as assessed by image analysis.
AB  - DNA content and chromatin supraorganization defined in terms of patterns of
      chromatin texture were studied by image analysis in Feulgen-stained human breast
      MCF-10F epithelial cells expressing different stages of tumorigenic progression
      after treatment with benzo[a]pyrene (BP). Nontransformed MCF-10F, nontumorigenic
      transformed BP1, and tumorigenic BP1-E1 cell lines were analyzed. A relationship
      between changes in DNA content and chromatin texture and the expression of
      different stages of tumorigenesis were researched in interphase nuclei. A
      significant decrease in Feulgen-DNA amounts and absorbing areas suggesting
      aneuploidy, and first detected in nontumorigenic transformed BP1 cells, became
      more relevant in the tumorigenic cell line BP1-E1. Simultaneously, an increase in
      optical densities and a change in related parameters, demonstrating increased
      chromatin higher order packing states, occurred in transformed BP1 cells and
      extended over larger chromatin areas in tumorigenic BP1-E1 cells. The results
      indicate loss of DNA and a change in chromatin higher order packing states
      accompanying the expression of different stages of the in vitro tumorigenesis
      process in BP-transformed human breast epithelial cells. It is suspected that the
      gradually acquired chromatin "condensation" supraorganization pattern is
      associated with activated transcription activities previously suggested for these
      cells.

PMID- 9770352
TI  - Phosphorylation of retinoblastoma protein assayed in individual HL-60 cells
      during their proliferation and differentiation.
AB  - Expression of pRb and its state of phosphorylation were immunocytochemically
      assayed in individual HL-60 cells during their proliferation and after induction
      of differentiation, using mAb which detects hypophosphorylated pRb (pRbP-)
      combined with mAb which reacts with pRb regardless of its phosphorylation (total
      pRb; pRbT). Correlated measurements of pRbP-, pRbT, a ratio of pRbP-/pRbT, and
      cellular DNA content by flow cytometry revealed expression of total pRb and its
      phosphorylation state vis-a-vis the cell cycle position. Following mitosis
      (during the exponential phase of cell growth) a mixture of hypo- and
      hyperphosphorylated pRb was present within the cell for less than 2 h, i.e.,
      early in G1; no hypophosphorylated pRb was detected throughout remainder of the
      cycle. Cellular pRb content was increasing primarily during G1 and the cell
      entrance to S was correlated with attainment of a distinct threshold level of
      pRb. No correlation was seen between the content of pRb per cell and its state of
      phosphorylation during G1. Cell differentiation whether induced by 1,25
      dihydroxyvitamin D3, retinoic acid, or phorbol myristate acetate led to cell
      arrest primarily in G0/1. The G0/1 cells in these cultures, compared to G1 cells
      from the untreated cultures, had increased level of both pRbT and pRbP-. However,
      because the relative increase of pRbP- was disproportionally greater than of
      pRbT, the pRbP-/pRbT ratio of the differentiating cells was markedly elevated.
      The cells that still were in S and G2/M in the differentiating cultures also
      showed the presence of hypophosphorylated pRb. Our data suggest that the
      mechanism of irreversible cell cycle arrest during terminal differentiation
      involves both the increase in content of pRb and dephosphorylation of pRb already
      present within the cell. This provides a large pool of hypophosphorylated pRb
      that can effectively remove all free E2F, thereby precluding activation of the
      genes whose transcription is needed to pass the G1 restriction point. In contrast
      to terminal differentiation the transient quiescence (G0 state) manifests only by
      dephosphorylation of pRb, without a change in its cellular level.

PMID- 9770353
TI  - Differential expression and distribution of focal adhesion and cell adhesion
      molecules in rat hepatocyte differentiation.
AB  - Hepatocytes in primary culture enter into clonal proliferation in the chemically
      defined hepatocyte growth medium in the presence of hepatocyte growth factor and
      epidermal growth factor. Hepatocyte proliferation is associated with loss of
      differentiated gene expression. Overlay of matrix derived from Engelbreth-Holm
      Swarm mouse sarcoma (Matrigel) on proliferating hepatocytes induces reexpression
      of the hepatic differentiation marker genes. To explore the role of matrix in the
      differentiation process of hepatocytes, we examined the mRNAs of fibronectin,
      vitronectin, and entactin in proliferating hepatocytes and Matrigel-treated
      hepatocytes. Fibronectin mRNA increased in proliferating hepatocytes at days 2-10
      and then decreased; however, vitronectin mRNA disappeared in proliferating
      hepatocytes and was reexpressed in Matrigel-treated hepatocytes. We also found
      that focal adhesion kinase and paxillin were strongly increased in Matrigel
      treated hepatocytes, and E-cadherin and beta-catenin slightly increased in
      Matrigel-treated hepatocytes, suggesting that both cell-to-extracellular matrix
      and cell-to-cell interactions may be an essential part of hepatocyte
      differentiation. To evaluate the distribution of focal adhesion associated
      molecules and cell-to-cell adhesion molecules, Triton X-100 soluble and insoluble
      fractions were examined at days 8, 9, 10, and 11 in proliferating hepatocytes and
      Matrigel-treated cells. We found that E-cadherin in Triton X-100 insoluble
      fractions dramatically decreased in Matrigel-treated hepatocytes; however, beta
      catenin strongly increased in Triton X-100 soluble fractions of Matrigel-treated
      hepatocytes. These results suggest that the distribution of both focal adhesion
      associated molecules and cell adhesion molecules are reorganized during the
      process of differentiation induced by overlay of Matrigel.

PMID- 9770354
TI  - Evidence of a functional role for the cyclin-dependent kinase inhibitor
      p21(WAF1/CIP1/MDA6) in the reciprocal regulation of PKC activator-induced
      apoptosis and differentation in human myelomonocytic leukemia cells.
AB  - The functional role of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) in
      leukemic cell G1 arrest, differentiation, and apoptosis induced by two PKC
      activators (PMA and bryostatin 1) was examined using antisense-expressing lines
      [U937/p21AS(F4) and U937/p21AS(B8)]. Following incubation with 10 nM PMA (24 h),
      antisense-expressing cells displayed induction of p27(KIP1) but not of p21,
      whereas empty vector-containing cells (U937/pREP4) exhibited induction of both
      p21 and p27. Antisense-expressing cells were impaired in G1 arrest,
      dephosphorylation of the retinoblastoma protein, dephosphorylation and reduction
      in activity of cyclin-dependent kinase 2, and acquisition of differentiated
      features (e.g., plastic adherence). Bryostatin 1 induced p27 but not p21 in
      control cells and was less effective than PMA in initiating G1 arrest and related
      events. Nevertheless, disruption of p21 expression abrogated the effects of
      bryostatin 1 on cell cycle arrest and cellular maturation. Dysregulation of p21
      did not, however, modify PMA- or bryostatin 1-mediated down-regulation of c-Myc
      protein. Unexpectedly, disruption of p21 failed to attenuate the net reduction in
      viable cell number following PMA or bryostatin 1 treatment inasmuch as impaired
      differentiation was accompanied by a lowered threshold for PMA- and bryostatin 1
      induced apoptosis. Inhibition of p21 expression also promoted PMA- and bryostatin
      1-mediated loss of mitochondrial transmembrane potential (DeltaPsim ) and release
      of cytochrome c into the cytosol. Together, these findings demonstrate a critical
      functional role for p21 in regulating myelomonocytic leukemic cell G1 arrest and
      differentiation following exposure to two PKC activators exhibiting disparate
      patterns of activity. They also suggest that following treatment with these
      agents, dysregulation of p21 prevents leukemic cells from engaging a normal
      differentiation program through a c-Myc-independent mechanism, and instead
      directs cells along an apoptotic pathway.

PMID- 9770355
TI  - Activation of cAMP-dependent protein kinase is required for optimal alpha
      melanocyte-stimulating hormone-induced pigmentation.
AB  - The cAMP-dependent pathway has been long presumed to play a critical role in
      mediating alpha-melanocyte-stimulating hormone (alpha-MSH)-induced pigmentation,
      but it has never been demonstrated that this pathway is obligatory. In order to
      determine whether the cAMP-dependent pathway is required for a alpha-MSH-induced
      pigmentation, we inhibited the activity of cAMP-dependent protein kinase (PKA),
      the main kinase mediating in this pathway, by introducing a physiologic cAMP
      dependent protein kinase inhibitor (PKI) into S91 murine melanoma cells and then
      measuring pigment response after alpha-MSH stimulation. Cells were stably
      transfected either with the pMXX-PKI expression vector that encodes the active
      part of PKI (the amino terminal 1-31 amino acids) under a metallothionein
      inducible promoter and the pSV2-Neo expression vector alone. As expected,
      treatment of transfected cells with 1 microM CdCl2 for 24 h induced the
      expression of PKI mRNA in cells transfected with both vectors, but not in cells
      transfected with the pSV2-Neo expression vector alone. Subsequent treatment of
      these transfected cells with alpha-MSH for 5-6 days in the continual presence of
      1 microM CdCl2 resulted in inhibition of PKA activity by 30-40% in cells
      expressing PKI. Parallel measurements revealed that alpha-MSH-increased melanin
      content five- to six-fold in control cells transfected with pSV2-Neo alone, while
      there was only a two-fold increase in PKI-expressing cells, a 40-50% inhibition
      in alpha-MSH-induced total melanin content. alpha-MSH-induced tyrosinase activity
      and tyrosinase mRNA and protein levels measured in parallel were also inhibited
      by 40-50% in PKI-expressing cells compared to control cells transfected with pSV2
      Neo alone. Together, these results demonstrate for the first time that activation
      of PKA through the cAMP-dependent pathway is required for optimal alpha-MSH
      induced pigmentation.

PMID- 9770356
TI  - Efficient gene trap screening for novel developmental genes using IRES beta geo
      vector and in vitro preselection.
AB  - We have used different gene trap vectors and in vitro preselection of embryonic
      stem (ES) cells for a large scale screening of insertional mutations in
      developmentally regulated genes. A gene trap vector was constructed, which
      contains an internal ribosome entry site (IRES) upstream from a betageo
      selectable-reporter fusion gene. Analysis of 801 independent integrations
      revealed that the IRESbetageo vector allows for a global enrichment of about 15
      folds in the number of detectable gene trap events when compared with a
      conventional betageo vector. Characterization of in vitro and in vivo lacZ
      expression suggested that this IRES-based vector is able to capture a wide range
      of genes expressed in a variety of tissues and developmental stages, and it can
      also allow trapping of genes expressed at very low levels in ES cells. A
      preselection protocol was devised, where gene-trapped ES cells were grown in the
      presence of specific growth/differentiation factors such as follistatin, nerve
      growth factor, and retinoic acid. Several gene trap integrations were found to be
      either activated or repressed by one of these factors. Characterization of lacZ
      expression during embryogenesis showed a strong enrichment of restricted patterns
      in vivo after ES cell preselection. These results suggest that a combination of
      IRESbetageo vector and in vitro preselection is more effective for the capture
      and mutation of a large number of developmental genes.

PMID- 9770357
TI  - Binding of human IgG and F(ab')2 and Fc fragments to cultured trophoblast cells
      from human term placenta.
AB  - Trophoblast cells, dispersed by trypsin digestion of human term placental villi
      and purified on Percoll gradient, were maintained in serum-containing medium as
      monolayer cultures up to 7 days. The initially mononucleated cells, probably
      cytotrophoblasts, differentiated in culture within 90 h to multinucleated
      syncytiotrophoblast-like cells. The enigmatic binding of human immunoglobulin G
      (hIgG) to these cells was studied and compared to the well-known binding of hIgG
      to cultured human monocytes. Binding of hIgG to cultured trophoblasts at 4
      degreesC reached steady state by 0.5-1 h, increased about two- to threefold after
      90 h in culture and was linear throughout all concentrations tested (0.00067-132
      microM). Fc fragments and even F(ab')2 fragments were found to bind to a similar
      extent to trophoblasts as the complete hIgG molecules. In contrast, in
      experiments with cultured monocytes, saturation of hIgG binding could be
      demonstrated. The binding of complete hIgG molecules and of Fc fragments to
      monocytes was similar whereas binding of F(ab')2 fragments to monocytes was
      significantly lower. Our results suggest that, despite morphological and at least
      partially functional differentiation of trophoblast cells in primary culture, no
      measurable amounts of functional Fc receptor for monomeric hIgG was expressed.

PMID- 9770358
TI  - Autocrine-paracrine regulation of human trophoblast invasiveness by insulin-like
      growth factor (IGF)-II and IGF-binding protein (IGFBP)-1.
AB  - Trophoblast growth and invasion of the uterus are tightly regulated by locally
      produced factors. Since insulin-like growth factor (IGF)-II is produced by the
      invasive human extravillous trophoblast (EVT) cells and IGF-binding protein
      (IGFBP)-1 by the decidual cells in situ that are in proximity to each other, we
      examined the possible influence of these molecules on proliferation, migration,
      and invasiveness of first-trimester EVT cells in culture. These EVT cell
      functions were respectively measured by 3H-TdR uptake, in vitro migration, and
      invasion assays. Secretion of invasion-associated enzymes was assessed by
      zymography, and IGF-binding moieties on the EVT cell were examined by affinity
      cross-linking. Proliferation of serum-starved EVT cells was stimulated by
      addition of serum but unaffected by a wide range of IGF-I, IGF-II, and IGFBP-1
      concentrations. IGF-II and IGFBP-1 or their combination stimulated EVT cell
      invasiveness and migration, when assays were conducted in serum-reduced media.
      Affinity cross-linking studies failed to detect the type 1 IGF receptor, although
      several IGF-II-specific and IGF-II-preferring binding molecules including type 2
      IGF receptor were identified on the EVT cell surface. IGF-II enhancement of
      invasion was unaffected in the presence of IGF-1 receptor-blocking antibody and
      IGF-1 failed to influence EVT cell invasion, indicating that type 1 IGF receptor
      was not responsible for the IGF-II effects. Secretion of gelatinases or
      plasminogen activators was unaltered by IGF-II or IGFBP-1. We conclude that
      trophoblast-derived IGF-II and decidua-derived IGFBP-1 provide
      autocrine/paracrine enhancement of trophoblast invasiveness largely by
      stimulating migration, an essential step in invasion.

PMID- 9770359
TI  - Regulation of expression and activity of distinct pRB, E2F, D-type cyclin, and
      CKI family members during terminal differentiation of P19 cells.
AB  - The cell cycle regulatory proteins, which include cyclin-dependent kinases
      (cdks), cdk inhibitors (CKIs), cyclins, and the pRB, and E2F families of
      proteins, constitute a network of interacting factors which govern exit from or
      passage through the mammalian cell cycle. While the proteins within these
      families have similar structural characteristics, each family member exhibits
      distinct expression patterns during embryogenesis and distinct biological
      activities. In order to begin to understand the tissue-specific roles of these
      interacting factors, we determined the expression pattern and activity of the
      pRB, E2F, cyclin, cdk, and CKI families of cell cycle regulatory proteins during
      retinoic acid-induced (neuronal pathway) and DMSO-induced (cardiac muscle
      pathway) differentiation of the pluripotent murine embryonal carcinoma cell line,
      P19. We demonstrate here that P19 terminal differentiation causes lineage
      specific changes in the expression and activity of distinct members of the E2F,
      pRB, cyclin, and CKI families. Furthermore, dynamic changes in the activities of
      these cell cycle regulatory proteins occur through several overlapping
      mechanisms, culminating in repression of DNA-binding activity by all of the E2F
      family members as cells terminally differentiate.

PMID- 9770360
TI  - A RanBP1 mutation which does not visibly affect nuclear import may reveal
      additional functions of the ran GTPase system.
AB  - Ran, a nuclear GTPase, and a number of interacting proteins, including regulators
      RanGEF1 and RanGAP1, are involved in nucleocytoplasmic transport. We have
      identified a new temperature-sensitive mutation in budding yeast YRB1 gene, which
      encodes Ran-binding protein-1 (RanBP1). In contrast to other yrb1 alleles, the
      new mutation (yrb1-21) does not cause visible defects in import of nuclear
      proteins Npl3p, histone H2B, or beta-galactosidase fused to a nuclear
      localization signal. We hypothesize that the inviability of mutant cells at the
      restrictive temperature is caused by an additional essential function of RanBP1
      other than nuclear import. This function may be revealed by the terminal
      phenotypes of yrb1-21, which include failure of the mitotic spindles to properly
      align along the mother-bud axis and accumulation of cells in late mitosis or G1
      phase of the cell cycle. These features are shared, in part, by a mutation in
      RanGEF1, but not in RanGAP1. The yrb1-21 allele suppresses a RanGEF1 mutation,
      indicating that RanGEF1 and RanBP1 may be involved in the same essential
      function.

PMID- 9770361
TI  - Selection and extended growth of murine epidermal stem cells in culture.
AB  - Continuously renewing epithelia contain small undifferentiated stem cells capable
      of self-renewal and maintenance of the differentiating cell population. In murine
      epidermis stem cells have been identified as label-retaining cells (LRCs) by long
      term retention of tritiated thymidine or BrdU. It has been suggested that
      epidermal stem cells adhere to basement membranes through differential expression
      of specific integrins. To determine whether we could use a specific integrin to
      enrich for murine epidermal stem cells, we tested adherence of LRCs to several
      substrates. Regardless of the substrate used, approximately 10% of total basal
      cells and 100% of LRCs adhered in 10 min. In our medium specifically formulated
      for murine keratinocytes, rapidly adherent stem cells formed large colonies and
      could be used to form a structurally complete epidermis in organotypic culture.
      They showed a fivefold greater transient transfection efficiency than total basal
      cells, and when individual adherent cells were transduced with a retroviral
      vector, they formed large clones. Although these stem cells grew more slowly than
      the total basal cell population, they could be subcultured more times. Our
      results indicate that murine epidermal stem cells can be selected by rapid
      attachment to a substrate, but not by one specific integrin, and that they can be
      expanded in culture if the appropriate conditions are maintained.

PMID- 9770362
TI  - Arterial nerve growth factor (NGF) mRNA, protein, and vascular smooth muscle cell
      NGF secretion in hypertensive and hyperactive rats.
AB  - Elevated levels of nerve growth factor (NGF) protein and NGF mRNA have been
      reported in the vessels of spontaneously hypertensive rats (SHR: hypertensive,
      hyperactive) compared to Wistar-Kyoto (WKY) rats. Elevated NGF may be involved in
      the development of hypertension in SHRs. We examined vascular NGF mRNA and
      protein content and the regulation of NGF secretion by vascular smooth muscle
      cells (VSMCs) from two inbred strains (WKHT: hypertensive; WKHA: hyperactive)
      derived from SHRs and WKYs. Our goal was to determine if receptor-mediated
      defects in NGF regulation play a role in increased secretion of VSMC NGF from
      hypertensive animals. Tissue NGF mRNA content was determined by competitive,
      quantitative RT-PCR. Tissue NGF and NGF content in cultured VSMC-conditioned
      medium was quantified using a two-site ELISA. Tail artery NGF mRNA was elevated
      in WKHTs compared to WKHAs. Tissue NGF protein was elevated in WKHT aorta,
      mesenteric, and tail artery compared to WKHAs. Pharmacologically induced
      increases in NGF output were blocked with inhibition of transcription or protein
      synthesis. Basal NGF secretion by WKHT VSMCs was significantly higher than WKHAs.
      The observed increases in VSMC NGF output in SHRs over WKYs in response to beta
      adrenergic agents are not preserved in the WKHT:WKHA comparison. Protein kinase C
      dependent increases in SHR VSMC NGF appear in both WKHTs and WKHAs. In contrast,
      elevated NGF levels due to disturbances in alpha-adrenergic, peptidergic, and
      purinergic control of NGF output are features common to both genetic models of
      hypertension (SHR and WKHT). These results suggest that the defect in smooth
      muscle NGF metabolism observed in SHRs cosegregates with a hypertensive rather
      than a hyperactive phenotype. Moreover, altered receptor-mediated regulation
      (alpha-adrenergic, peptidergic, and purinergic) of VSMC NGF production may
      contribute to elevated vascular tissue NGF, suggesting a mechanism leading to the
      high levels of NGF associated with hypertension in SHRs and WKHTs.

PMID- 9770363
TI  - The histone H1(0) contains multiple sequence elements for nuclear targeting.
AB  - We have investigated the nuclear transport of the replacement histone H1(0) and
      have searched for its nuclear localization sequence (NLS). The lysine-rich H1(0)
      histone differs from the other H1 histones with respect to its mode of expression
      and to the processing of the respective mRNA. Using the digitonin-permeabilized
      cell import assay we demonstrate that H1(0) is transported into the nucleus in an
      energy- and temperature-dependent manner. In competition experiments we show that
      the transport of H1(0) from the cytoplasm into the nucleus is competed by the
      SV40 T-antigen-NLS-peptide coupled to HSA, an established substrate of the
      importin pathway. In transfection studies we have expressed in HeLa cells a
      series of plasmid constructs containing different fragments of the coding region
      of the H1(0) histone gene that were fused to the beta-galactosidase gene, and we
      have determined the subcellular localization of each fusion protein. The results
      show that H1(0) contains multiple transport-competent sequence elements that can
      function as NLS and that H1(0) meets the requirements for a transport into the
      nucleus by an importin-dependent pathway.

PMID- 9770364
TI  - Mode of cell injury and death after hydrogen peroxide exposure in cultured
      oligodendroglia cells.
AB  - Oxidative stress has been implicated as a causal factor in a wide variety of
      neurodegenerative diseases. To investigate the direct consequences of oxidative
      damage on myelin-forming cells, we have exposed oligodendrocytes to hydrogen
      peroxide. Cytotoxicity was assessed in glial cultures by neutral red (NR) and MTT
      assay, and half-maximal cytotoxicity was reached after a 30-min application with
      100-200 microM H2O2 during a 16-24-h recovery period. The cytotoxic effect could
      be partly abolished by the simultaneous incubation with N-acetyl-l-cysteine, an
      antioxidant and precursor of glutathione. In purified mature oligodendroglia
      cultures (7 div), metabolic activity as determined by the MTT assay, was impaired
      directly after the treatment with H2O2, and only slightly further enhanced during
      the 24-h recovery period. Morphological inspection revealed that oligodendrocytes
      in either the presence or the absence of astrocytes were specifically susceptible
      to free radical damage, the membranous sheets were disrupted, membranous blebs
      appeared, and fragmented nuclei were seen. Similar changes were induced by
      treatment with menadione or staurosporine. The data show that brief exposure to
      H2O2 induced cell death via apoptosis. This death occurred over a period of 24 h
      and was accompanied by the appearance of fragmented and condensed DAPI-stained
      nuclei and internucleosomal DNA cleavage. Concomitantly, as investigated by RT
      PCR analysis, the transcriptional activity of c-fos and c-jun was stimulated,
      without altering mRNA expression of the myelin-specific genes MBP, MAG, and PLP.
      Thus, oxidative stress in oligodendrocytes leads to the onset of programmed cell
      death, involving the transcriptional activation of the immediate-early genes c
      fos and c-jun.

PMID- 9770365
TI  - Mesonephric stromal cells differentiate into Leydig cells in the mouse fetal
      testis.
AB  - Circumstantial evidence has suggested that Sry expression probably occurs in pre
      Sertoli cells, implying that they produce signals required for testis
      differentiation. From experiments involving gonad/mesonephros grafts it has been
      shown that, at 11.5 days postcoitum stromal cells from the mesonephros invade the
      male gonad. Although in the grafted testes, Leydig cells appeared among the
      stromal cells, in these studies their origin remained elusive. In the current
      study, we reconstructed urogenital ridges in organ culture by grafting
      morphologically undifferentiated male genital ridges from CD-1 embryos, to
      mesonephroi from ROSA26 transgenic embryos whose cells express the bacterial beta
      galactosidase. With an improved technique for the detection of beta-gal enzyme
      activity in electronmicrographs, we studied cell migration and differentiation of
      mesonephric cells into the testis in reconstructed urogenital ridges with XY or
      XX mesonephroi. It was found that, in addition to differentiation of myoid and
      connective cells, some migratory mesonephric cells acquired ultrastructural
      features of steroidogenic Leydig cells. Several beta-gal positive cells
      differentiated as Leydig cells in gonads grafted with either male or female
      mesonephros. The results suggest that mesonephric cells responded to putative
      signal(s) produced in the male gonad and participate in morphogenesis and cell
      differentiation of the fetal testis.

PMID- 9770366
TI  - Antisense modulation of the ICAM-1 phenotype of a model human bone marrow stromal
      cell line.
AB  - Efficient stable gene transfer was achieved in a model human bone marrow stromal
      cell line, KM-102, using both Epstein-Barr virus and BK virus episomal expression
      vectors. Using this episomal expression system, effective overexpression and
      inhibition of ICAM-1 expression was achieved in stably transfected KM-102 cells
      by sense and antisense RNA gene transfer, respectively. Loss of surface ICAM-1 on
      antisense KM-102 transfectants did not significantly affect adhesion to LFA-1
      bearing JY hematopoietic cells. However, KM-102 ICAM-1 overexpressors
      demonstrated enhanced binding (2.5-fold) to phorbol ester-treated, but not
      untreated, LFA-1-bearing JY cells. The increased binding could be blocked with
      anti-ICAM-1 antibodies. These findings suggest that while ICAM-1 is not required
      for basal adhesion between stromal and hematopoietic cells, stromal ICAM-1 may
      contribute to stromal:leukemic cellular interaction when bound to the phorbol
      ester-dependent high-avidity state of hematopoietic LFA-1.

PMID- 9770367
TI  - Differentiation markers and invasiveness: discordant regulation in normal
      trophoblast and choriocarcinoma cells.
AB  - In tumor cells, malignant (invasive) behavior and differentiation tend to be
      correlated inversely, although it is not clear to what extent this can be
      generalized and whether it may also apply to normal invasive cell types. We have
      modulated differentiation of normal trophoblast cells from first trimester or
      term placenta as well as choriocarcinoma cells (BeWo, Jeg-3, and JAr) with
      retinoic acid (RA), methotrexate (MTX), dibutyryl-cAMP (dbcAMP), or phorbol-[12
      myristoyl-13-acetyl]-diester (PMA). The secretion of the differentiation marker
      chorionic gonadotrophin was stimulated by nearly all substances in all cell
      types. The activity of cellular sterylsulfatase showed a tendency to be increased
      (decreased by RA and dbcAMP in normal trophoblast; not detected in JAr).
      Invasiveness was decreased by all effectors in normal trophoblast (both types)
      and in BeWo. In Jeg-3 and JAr, however, PMA treatment (in JAr also RA treatment)
      increased invasion rates. These results suggest that only in normal trophoblast
      and in BeWo (but not in other choriocarcinoma cells, i.e., Jeg-3 and JAr)
      invasiveness and differentiation tend to be correlated inversely. When
      extrapolating to the various subpopulations of cells within a tumor, induction of
      differentiation-as intended in certain strategies for tumor therapy
      ("differentiation therapy")-may have the unwanted effect of stimulating
      invasiveness in certain subpopulations of tumor cells.

PMID- 9770368
TI  - K562 erythroid and HL60 macrophage differentiation downregulates polycystin, a
      large membrane-associated protein.
AB  - Polycystin, the PKD1 gene product mutated in autosomal dominant polycystic kidney
      disease, is a large membrane protein which is important in the differentiation of
      epithelial tubular structure. Furthermore, PKD1 mRNA is expressed in various
      tissues and in neoplastic cell lines particularly, suggesting that polycystin
      might be involved in differentiation and/or proliferation of other cell types.
      Therefore, in order to investigate such a possible role, polyclonal antibodies
      against a recombinant polycystin peptide were raised and used to study polycystin
      expression in human leukemia cell lines committed to differentiation. Using
      Western blot and laser scanning confocal microscopy analyses, we demonstrated
      expression of polycystin in erythroleukemia K562 cells as a membrane-associated
      polypeptide of approximately 450 kDa, mainly localized in cell-cell contacts.
      Protein size and subcellular distribution were similar to those found in the
      kidney epithelial KJ29 cell line. In addition, K562 cell erythroid
      differentiation induced by hemin was characterized by a reduction in polycystin
      expression, as measured by Western blot and Northern blot analyses.
      Cytofluorimetric analysis indicated that upon hemin treatment there was a
      progressive reduction in the number of polycystin-expressing cells as well as in
      proliferation rate. Furthermore, reduction in proliferating and polycystin
      expressing cells was also observed in K562 cells after serum starvation. When
      serum was added to the serum-deprived cells an increase in cell number as well as
      in number of polycystin-positive cells was observed. In addition, polycystin,
      also expressed in promyelocytic leukemia HL60 cells, was downregulated when
      macrophage differentiation in HL60 was induced by TPA. Therefore, in these
      leukemic cells downregulation of polycystin appeared to be closely related to
      reduction in cell proliferation and to induction of differentiation. This
      suggests that polycystin may play a relevant role in these cell processes.

PMID- 9770370
TI  - Cellular and cytoskeleton morphology and strength of adhesion of cells on self
      assembled monolayers of organosilanes.
AB  - The objective of this study was to explore the potential use of self-assembled
      monolayers (SAMs) of alkylamine and arylalkyamine as well-defined, homogeneous,
      tailored in vitro model surfaces for exploring the effect of hydrodynamic flow on
      morphology and strength of adhesion of human umbilical vein endothelial cells.
      The cell surface area, shape, f-actin distribution, and adhesion strength of
      human umbilical vein endothelial cells cultured on self-assembled monolayers of
      organosilanes were found to be dependent on the chemical composition of the
      organosilane film and the magnitude of wall shear stress. The direct effects of
      the differences in chemistry between the two silanes, in modulating cellular
      response, are probably only secondary to the modulation of cellular functions
      mediated by differential protein adsorption and conformation on the two silanes.
      For short seeding times (30 min), prior to application of flow, both substrate
      chemistry and shear stress modulated the cellular morphology and cytoskeletal
      organization. For longer seeding times (24 h), prior to application of flow, the
      chemistry of the underlying surface was the dominant variable in modulating
      cellular morphology, while the hydrodynamic shear stress modulated the
      cytoskeleton organization. Cells on N-(2-aminoethyl)-3-aminopropyl
      trimethoxysilane (EDA) were pleomorphic, while cells on
      ((((aminoethyl)amino)methyl)phenylethyl)trimethoxysilane (PEDA) expressed a
      rounded morphology. Application of an incrementally loaded flow regime (0.07-1.25
      ml/s) resulted in a time- and shear stress-dependent (10-180 dyn/cm2) detachment
      of cells, with the cells on EDA depicting higher resistance to wall shear stress.
      Cellular morphology correlated with the strength of adhesion; cells with rounded
      morphology on a hydrophobic silane, PEDA, were less tightly bound to the silane,
      while spread cells on a hydrophilic silane, EDA, were more tightly bound. The
      higher surface free energy of EDA is speculated to influence the increased cell
      spreading and strength of adhesion observed in these studies. The presence of the
      phenyl group in PEDA reduces the surface free energy and may account for the
      reduced spreading and lower strength of adhesion. The use of well-defined
      systems, such as monolayer organosilanes, with tunable surface physicochemical
      properties may serve to deconstruct the complex interaction of cells with
      extracellular matrix components: surface charge, surface hydrophobicity, and
      other short- and long-range forces can be individually controlled and correlated
      with cellular functions. The organosilane monolayers could serve as the building
      blocks for sequential addition of proteins or cell adhesive/cell repulsive cues
      to stepwise engineering and construction of more complex systems resembling ECM
      matrices.

PMID- 9770369
TI  - Telomere length regulation--a view from the individual chromosome perspective.
AB  - Telomeres are specialized structures at chromosome termini implicated in
      oncogenesis and cellular aging. Since both phenomena are related to variations in
      telomere length it is of interest to understand mechanisms responsible for
      telomere length regulation. Recent studies in mammalian cells indicate that
      specific chromosomes may have specific telomere lengths, suggesting the existence
      of chromosome-specific factors involved in telomere length regulation. Although
      these chromosome-specific factors are largely unknown at present, in the mouse
      evidence suggests a possible role of centromere position in telomere length
      regulation-telomeres closer to centromeres (i.e., p-arm telomeres) are
      significantly shorter than their counterparts more distant from centromeres
      (i.e., q-arm telomeres). The mouse may be a special case because its karyotype
      consists almost exclusively of acrocentric chromosomes in which p-arm telomeres
      and centromeres are located immediately adjacent to each other. However, a weak
      correlation between telomere length and centromere position is observed in the
      case of nonacrocentric human and Chinese hamster chromosomes, suggesting that the
      putative centromere position effect might be evolutionarily conserved.
      Alternatively, telomere length in individual nonacrocentric chromosomes may be
      affected by the sequence organization of subtelomeric chromosome regions or by
      some other, currently unknown, factors.

PMID- 9770372
TI  - Inhibition of cyclin D-cdk activity in cell cycle arrest of Swiss 3T3 cells by
      CeReS-18, a novel cell regulatory sialoglycopeptide.
AB  - CeReS-18 is a unique negative regulator of cell proliferation with a wide array
      of target cells. To elucidate the mechanism by which CeReS-18 mediates cell
      growth inhibition, the possibility that CeReS-18 alters the function of G1
      cyclins and their respective cyclin-dependent kinases (cdks) has been examined in
      mouse fibroblasts (Swiss 3T3) synchronized by CeReS-18. We show here that cyclin
      D-associated cdk activity is significantly inhibited in the CeReS-18-treated
      cells. Corresponding to the inhibited cdk function, we demonstrate a low
      expression of cyclin D in mid G1 determined by Western blot analysis, and cyclin
      D was greatly reduced in the immunocomplex recovered with antibody to cdk4 and
      cdk6. Previously, we have shown that the retinoblastoma susceptibility gene
      product (pRb), a key substrate of cyclin D-cdk complex, was maintained in the
      hypophosphorylated state in the CeReS-18-inhibited cells. We conclude here that
      cyclin D/cdk4,6/pRb is the major pathway by which CeReS-18 mediates cell cycle
      arrest.

PMID- 9770371
TI  - Ionic control of chromosome architecture in living and permeabilized cells.
AB  - Studies with isolated chromatin show that higher order chromosome architecture
      can be regulated by ionic conditions; however, the physiological relevance of
      these findings remains unknown. In the present study, chromosome architecture was
      analyzed in situ in living and detergent-extracted cells exposed to different
      ionic conditions. In intact mitotic endothelial cells, chromosomes instantly
      unfolded as detected by phase contrast microscopy when the salt concentration in
      the culture medium was increased from 110 to 410 mM NaCl or from 0 to 65 mM
      MgCl2. When the ions were removed and the preexisting culture conditions were
      restored, chromosomes refolded into their original shapes and subsequently
      underwent mitotic division. Similar reversible effects were observed on nucleolar
      structure in living interphase cells as well as on mitotic chromosomes exposed to
      high salt after cell membranes were removed by treatment with Triton X-100. This
      permeabilized mitotic cell model was then used to identify proteins that remained
      tightly associated with chromatin during the ion-driven chromosome unfolding
      refolding cycle and which therefore could be important for maintenance of
      chromosome structure. Under these conditions in which disassembled chromosomes
      retained their ability to fully recondense, more than 95% of Topoisomerase I was
      extracted whereas approximately 25% of Topoisomerase IIalpha and 50% of Histone
      H1 remained tightly associated with chromatin. These data demonstrate the
      sensitivity of chromosome structure to variations in ionic concentration in situ
      and suggest that there are at least two distinct pools of Histone H1 and
      Topoisomerase IIalpha associated with chromatin during mitosis, one of which may
      be required for chromosome compaction.

PMID- 9770374
TI  - PLA2 activity regulates Ca2+ storage-dependent cellular proliferation.
AB  - The objective of this study is to determine the role of arachidonic acid (AA) in
      cell proliferation by inhibiting AA synthetic enzyme phospholipase A2 (PLA2) and
      to determine its involvement in the role of the second messenger intracellular
      calcium (Ca2+). Methods used to determine the effects on proliferation of cell
      cultures of primary meningioma and astrocytoma U373-MG included treatment with
      micromolar concentrations of PLA2 inhibitors 4-bromophenacylbromide and
      quinacrine. Effects of these drugs on proliferation were further investigated by
      the application of concentrations that inhibit growth by 50% while antagonizing
      these agents with AA replacement. Free cytosolic Ca2+ was measured with the use
      of fluorescent dye Fura-2 during PLA2 agonist/antagonist studies. These Ca2+
      measurements were performed in the absence of extracellular Ca2+ to identify the
      contribution of intracellular Ca2+ sources. PLA2 inhibition resulted in decreased
      growth of cultured astrocytoma and meningioma cells in a dose-dependent manner in
      the micromolar range. This inhibitory effect was antagonized by the addition of
      AA. PLA2 inhibition caused an elevation of basal-cytosolic-free [Ca2+] while
      depleting internal Ca2+ stores. These Ca2+ changes were also antagonized by the
      addition of AA. In conclusion, these results demonstrate that AA, a PLA2 enzyme
      product, is involved in regulating the growth rate of these cell types. The PLA2
      pathway also regulates the maintenance of the internal Ca2+ stores. Ca2+ is known
      to be a growth-related intracellular second messenger. These results suggest that
      the growth regulatory functions of AA are mediated by Ca2+-dependent mechanisms.

PMID- 9770373
TI  - Caspase-3-like activity is necessary for IL-2 release in activated Jurkat T
      cells.
AB  - The caspase family of proteases has previously been implicated in the biochemical
      cascade leading to apoptotic cell death. Recently caspase-3 was reported to be
      cleaved into its catalytically active subunits (17 and 13 kDa) following
      phytohemagglutinin (PHA) activation of peripheral blood mononuclear cells (C.
      Miossec et al., J. Biol. Chem. 272, 13459-13462). More recently, J. M. Zapata and
      colleagues (J. Biol. Chem. 273, 6916-6920, 1998), however, proposed that caspase
      3 activity detected during T-cell activation was due to a methodological artifact
      related to the composition of the cell lysis buffer. Here we show that in PHA
      activated Jurkat T-cells using the recommended lysis buffer detailed by Zapata et
      al., a caspase-3-like protease is activated and is accompanied by cleavage of
      PARP and alpha-spectrin into cleavage products suggestive of caspase-3
      proteolytic activation. LDH release did not increase following PHA stimulation in
      this paradigm. Two caspase inhibitors, carbobenzoxy-Asp-CH2OC(O)-2,6
      dichlorobenzene (Z-D-DCB) and acetyl-Asp-Glu-Val-Asp-CHO, blocked IL-2 release in
      a dose-dependent manner. Caspase-3-like protease-generated PARP and alpha
      spectrin breakdown product formation was also reduced by Z-D-DCB. In addition,
      Jurkat T-cells costimulated with anti-CD3 plus anti-CD28 produced significant
      levels of IL-2 that were also blocked by these caspase inhibitors. Importantly,
      IL-2 was determined in cell culture supernatants, thus avoiding a cell lysis step
      that might have enabled activation of caspase-3 by granzyme B. Collectively,
      these data support the role of caspase-3-like protease activity in Jurkat T-cell
      activation and demonstrate that caspase-3 like activity is necessary for IL-2
      release in PHA-activated and anti-CD3/anti-CD28 costimulated Jurkat T-cells.

PMID- 9770375
TI  - Normal tyrosine transport and abnormal tyrosinase routing in pink-eyed dilution
      melanocytes.
AB  - The pink-eyed dilution phenotype in mice arises from mutations in the p gene; in
      humans, analogous mutations in the P gene result in oculocutaneous albinism type
      2. Although the molecular mechanisms which underlie this phenotype remain
      obscure, it has been postulated that mutations in p result in defective tyrosine
      transport into murine melanosomes, resulting in hypopigmentation and diminished
      coat color. However, we previously reported no difference in melanosomal tyrosine
      transport in unpigmented, melanoblast-like pink-eyed dilution (pcp/pcp), and in
      pigmented (melan-a) murine melanocytes. In this study, we utilized melan-p1
      cells, more differentiated pink-eyed dilution (pcp/p25H) melanocytes which can be
      induced to produce melanin, to characterize the melanogenic lesion(s) more
      definitively. Uptake of [3H]tyrosine into melan-a melanosomes did not differ
      significantly from uptake into melanosomes derived from melan-p1 melanocytes,
      further arguing against its critical role as a tyrosine transporter. Pink-eyed
      dilution melanocytes incubated in high tyrosine concentrations became extremely
      pigmented as they became confluent and secreted large amounts of black material
      into the medium. Total cellular tyrosinase activity in melan-p1 melanocytes was
      significantly higher than that in melan-a melanocytes (which are wild-type at the
      p locus), but the localization of tyrosinase to melanosomes was impaired in melan
      p1 melanocytes compared to melan-a melanocytes. These results indicate that
      mechanisms other than deficient tyrosine transport are involved in the pink-eyed
      dilution phenotype and that this protein may serve a chaperone-like or
      stabilizing function in melanocytes.

PMID- 9770377
TI  - Cytoskeletal association of an esterase in Dictyostelium discoideum.
AB  - A 70-kDa glycoprotein, gp70, was found enriched in the detergent-insoluble
      cytoskeletal fraction of axenically grown Dictyostelium discoideum cells. Its N
      terminal amino acid sequence identified it as 'crystal protein' (L. Bomblies et
      al., 1990, J. Cell Biol. 110, 669-679). This finding was corroborated when
      antibody to crystal protein cross-reacted with gp70 and its deglycosylated form.
      The postulated esterase activity of gp70/crystal protein was verified through
      comparative enzyme assays of extracts derived from cells that either
      overexpressed or lacked gp70. Gp70 cosedimented with cytoskeletons on sucrose
      gradients, suggesting an interaction with the cytoskeleton. Coisolation of gp70
      with detergent-extracted cells, observed by immunofluorescence microscopy, also
      implied a gp70-cytoskeletal association. These data supported the idea that the
      localization or secretion of gp70, or both, was cytoskeletally mediated. Although
      axenically grown cells contained high levels of gp70, the same cell lines had
      reduced levels of gp70 when grown in bacterial suspension or in nutrient media
      containing bacteria. Bacterially grown cells, compared to axenically grown cells,
      had lower fluid-phase uptake rates even when nutrient media was present,
      indicating that phagocytosis was a preferred mode of feeding. Thus, bacteria
      inhibited gp70 expression, which suggested a role for prestarvation factor, in
      regulating its synthesis.

PMID- 9770376
TI  - Agonist and antagonist-dependent internalization of the human vasopressin V2
      receptor.
AB  - In this report we demonstrate that in HEK293 cells stably expressing the human V2
      vasopressin receptor, ligand-induced internalization of the hormone receptor
      occurs via the clathrin-dependent pathway. Studies of receptor trafficking either
      by direct visualization of the V2 receptor by confocal microscopy or binding
      experiments show a rapid internalization (half-time 6-7 min). Blocking of the
      clathrin-dependent pathway by hypertonic sucrose increased vasopressin-induced
      cellular cAMP production and decreased the desensitization of the V2 receptor
      adenylyl cyclase system. Thus, internalization appears to be a major regulatory
      mechanism terminating vasopressin action in HEK293 cells. Two antagonists of the
      vasopressin V2 receptor exerted different effects on receptor internalization, as
      determined by confocal fluorescence microscopy. The nonpeptidic antagonist
      OPC31260 did not induce any visible receptor internalization, whereas the
      peptidic antagonist d(CH2)5[D-Tyr(Et)2,Val4,Lys8,Tyr-NH29]VP induced a slow but
      substantial receptor internalization. These results suggest that long-term
      treatment with peptidic V2 receptor antagonists might lead to desensitization.

PMID- 9770378
TI  - Transcriptional regulation of the EGF receptor promoter by HPV16 and retinoic
      acid in human ectocervical epithelial cells.
AB  - We have previously demonstrated that human papillomavirus 16 (HPV16)-immortalized
      human ectocervical epithelial cells and cells derived from tumors which express
      HPV16 oncogenes express high levels of epidermal growth factor receptor (EGFR)
      compared to normal cervical cells. We have also shown that proliferation of these
      cells is inhibited by retinoid treatment. We have hypothesized that the retinoid
      inhibition of cell proliferation may be due to the retinoid-dependent reduction
      in EGFR level. In this study we examine the regulation of EGFR expression in
      cervical cells with emphasis on two aspects: (1) the mechanism of retinoid
      dependent suppression of EGFR levels in HPV16-positive cells and (2) the
      mechanism of EGFR upregulation by HPV16. EGFR levels were found to be elevated 5
      , 3. 7-, and 1.25-fold in the HPV16-immortalized ECE16-1, ECE16-D1, and ECE16-D2
      cells, respectively, compared to normal cervical cells. Treatment of ECE16-1 and
      ECE16-D1 cells with retinoic acid suppresses proliferation, EGFR level, EGFR mRNA
      level, and EGFR promoter activity. The reduction in EGFR promoter activity
      appears to account for the reduction in EGFR protein and mRNA levels. In
      contrast, retinoic acid does not affect cell growth or EGFR level in ECE16-D2
      cells or normal cervical cells. To study the mechanisms regulating EGFR
      expression in HPV16-positive cells, normal ECE cells were cotransfected with an
      EGFR promoter reporter plasmid and an expression plasmid encoding the HPV16 E6/E7
      open reading frames. In the presence of E6/E7, EGFR promoter activity was
      increased by 2- to 3-fold, suggesting that the E6/E7 proteins are directly or
      indirectly responsible for the increased EGFR level and that the EGFR promoter
      contains the DNA elements necessary to mediate this response. Nevertheless
      expression of E6/E7 proteins did not confer retinoic acid regulation, as EGFR
      promoter activity remained elevated in normal cells cotransfected with pHPVE6/E7
      and treated with retinoic acid. These results suggest that human papillomavirus
      and retinoic acid regulate EGFR levels by independent effects on the EGFR
      promoter.

PMID- 9770379
TI  - Nuclear translocation and increased expression of Bax and disturbance in cell
      cycle progression without prominent apoptosis induced by hyperthermia.
AB  - Effects of hyperthermia at 42.5 degreesC for 6 h on cell survival, cell cycle
      progression, and the localization and expression levels of Bcl-2 and Bax, as well
      as the association between Bcl-2 and Bax in human lung cancer cells were
      investigated. Untreated human lung cancer cells, though immortalized, expressed
      Bax unlike peripheral lymphocytes with low Bax expression. Bcl-2 was localized
      only in the cytoplasm in all the cell lines tested, whereas Bax was localized in
      the cytoplasm and/or nucleus; (1) only in the nucleus in three cell lines, (2)
      either in the nucleus or the cytoplasm in three cell lines, (3) in both the
      nucleus and the cytoplasm in one cell line, and (4) only in the cytoplasm in
      three cell lines. Of 10 cell lines examined, 6 had a low sensitivity to
      hyperthermia with a viability of 50% or more, and four cell lines had a high
      sensitivity to hyperthermia with a viability of less than 50% regardless of cell
      type. In cell lines highly sensitive to hyperthermia, Bax was localized in the
      nucleus. Hyperthermia increased the cellular level of Bax, but not Bcl-2, and
      reduced the association between Bcl-2 and Bax expression in PC-10 cells. Although
      the Bax level increased, hyperthermia induced only mild apoptosis and caused
      prominent cell cycle disturbance, especially in the S and G2M phases. Thus,
      hyperthermia at 42.5 degreesC for 6 h had cytostatic effect as well as caused
      mild apoptosis. Interestingly, during 3 h of hyperthermia, Bax translocated from
      the cytoplasm to the nucleus, whereas Bcl-2 remained in the cytoplasm. These
      results raise the possibility that Bax may lose its function as the inducer of
      apoptosis by translocating into the nucleus or have an unknown role in the
      nucleus.

PMID- 9770381
TI  - Microwave Spectra of the Methylcyanopolyynes CH3(C&tbond;C)nCN, n = 2, 3, 4, 5.
AB  - The ground state rotational spectra of four methylcyanopolyynes
      CH3(C&tbond;C)2CN, CH3(C&tbond;C)3CN, CH3(C&tbond;C)4CN, and CH3(C&tbond;C)5CN
      were measured between 6 and 22 GHz by Fourier transform microwave spectroscopy.
      For CH3(C&tbond;C)2CN, previously observed by Alexander et al. [J. Mol.
      Spectrosc. 70, 84-94 (1978)] eight transitions were observed, each with
      sufficient resolution to determine the nitrogen quadrupole hyperfine constant for
      the first time: eqQ = -4.25(3) MHz. The longer three methylcyanopolyynes are new;
      for these, from 10 to 21 rotational transitions were detected and precise values
      for the rotational and the leading centrifugal distortion constants, and eqQ for
      CH3(C&tbond;C)3CN, were determined. Copyright 1998 Academic Press.

PMID- 9770380
TI  - A composite CMV-IE enhancer/beta-actin promoter is ubiquitously expressed in
      mouse cutaneous epithelium.
AB  - In most existing transgenic mouse models developed for the study of specific
      genes in the skin, the goal has been to target transgene expression to defined
      populations of cells in the cutaneous epithelium. Keratin promoters have been
      especially useful for this purpose. In some instances, however, it may be
      desirable to express a transgene in all the cells of the cutaneous epithelium.
      Since no ubiquitously expressed promoter sequences had previously been
      identified, we used lacZ reporter transgenes to test two enhancer/promoter
      sequences for ubiquitous expression in the skin of adult transgenic mice. We find
      that a CMV enhancer/CMV promoter is not active in most cell types in the skin,
      whereas a CMV enhancer/modified beta-actin promoter sequence is active in the
      suprabasal and basal cells of the epidermis as well as in the epithelial cells of
      the hair follicles, sebaceous glands, and the dermal papillae.

PMID- 9770382
TI  - Microwave Spectra of the Methylpolyynes CH3(C identical withC)4H and CH3(C
      identical withC)5H.
AB  - Following the laboratory detection by Fourier transform microwave spectroscopy of
      the four new methylcyanopolyynes described in the accompanying paper by W. Chen
      et al. (J. Mol. Spectrosc. 1998), we detected two new methylpolyynes, CH3(C
      identical withC)4H and CH3(C identical withC)5H. The strongest lines of both
      molecules, obtained in a discharge with a dilute mixture of methylacetylene and
      diacetylene in neon, were quite intense: after 4 min of integration, a signal to
      noise of about 300 for the strongest lines of CH3(C identical withC)4H and 30 for
      those of CH3(C identical withC)5H. Enough rotational transitions from the K = 0
      and 1 ladders were detected in either molecule to be confident of the
      identification and to determine the rotational and leading centrifugal distortion
      constants to high accuracy. Like other carbon chains, the two here may be
      important in combustion processes and may be detectable in the interstellar gas,
      where the two shortest methylpolyynes have already been observed. Copyright 1998
      Academic Press.

PMID- 9770383
TI  - Analysis of O2-Broadening of 12CH3F Lines in the 6.8-um Spectral Region.
AB  - Using a tunable diode-laser spectrometer, we have measured the O2-broadening
      coefficients for 45 lines of methyl fluoride in the QP and QR branches of the nu2
      parallel band, and in the PP, PQ, PR, RP, RQ, and RR branches of the nu5
      perpendicular band. These lines with J values ranging from 1 to 23 and K from 0
      to 9 (K </= J) are located in the spectral range 1416-1573 cm-1. The collisional
      halfwidths are obtained by modeling each spectral line with a Voigt and a Rautian
      profile. The noncorrelated Rautian model leads to larger values of broadening
      coefficients than the Voigt model. These coefficients have also been calculated
      from a semiclassical model in which the intermolecular potential includes
      electrostatic, induction, and dispersion energy contributions. The results in the
      P, Q, and R branches of the nu2 and nu5 bands are in overall agreement with the
      experimental data. Copyright 1998 Academic Press.

PMID- 9770384
TI  - Millimeter and Submillimeter-Wave Spectrum of Hydrogen Peroxide in the Ground and
      v3 = 1 Vibrational States.
AB  - The first measurements of the millimeter- and submillimeter (mm/submm)-wave
      rotational-torsional transitions in the v3 = 1 ground torsional state (n = 0) of
      hydrogen peroxide are reported. The 149 newly measured transitions extend from 72
      to 623 GHz in frequency and up to J = 32 and Ka = 3 in rotational quantum number.
      Additional measurements in the ground vibrational and torsional state around 1
      THz are also reported. These data, along with all previously published microwave,
      mm/submm-wave, and far infrared data in the ground and v3 = 1 vibrational state,
      along with recent infrared measurements, have been fitted simultaneously to their
      respective experimental uncertainties using a multi-state Hamiltonian that
      includes Fermi- and Coriolis-type interactions. Copyright 1998 Academic Press.

PMID- 9770385
TI  - The 4(3)Pig and 6(3)Pig States of Na2: Observation and Assignment.
AB  - Two 3Pig states of Na2 have been observed in the 35 000-38 000 cm-1 energy region
      by pulsed perturbation facilitated optical-optical double resonance (PFOODR)
      fluorescence excitation spectroscopy and assigned to the 5dpi and 6dpi (the
      fourth and sixth according to the energy rank at Re) 3Pig Rydberg states,
      respectively. Molecular constants and RKR potential curves are reported.
      Copyright 1998 Academic Press.

PMID- 9770386
TI  - Transition Dipole Moments for the Vibrational Fundamentals of HNC Determined from
      the Herman-Wallis Effect.
AB  - The nu1 and nu3 fundamental bands of HNC are recorded with a Fourier transform
      infrared spectrometer with a resolution of 0.008 cm-1. Hydrogen isocyanide is
      generated in situ by dc discharge in a mixture of CH3CN ( approximately 40
      mTorr), H2 ( approximately 160 mTorr), and Ar ( approximately 160 mTorr). The
      transition dipole moments for these fundamental bands are determined from the
      analysis of the Herman-Wallis effect, and they are compared with ab initio
      calculated values. It is found that the ab initio values for the nu1 and nu3
      bands are about 50 and 30% larger, respectively. The transition dipole moments
      determined are to be of use for determination of the abundance of HNC in reaction
      systems such as the dissociative recombination reaction of HCNH+ with electrons.
      Copyright 1998 Academic Press.

PMID- 9770387
TI  - High-Resolution Study of the First Stretching Overtones of H3Si79Br.
AB  - The Fourier transform infrared spectrum of monoisotopic H3Si79Br (resolution 7.7
      x 10(-3) cm-1) was studied from 4200 to 4520 cm-1, in the region of the first
      overtones of the Si-H stretching vibration. The investigation of the spectrum
      revealed the presence of two band systems, the first consisting of one parallel
      (nu0 = 4340.2002 cm-1) and one perpendicular (nu0 = 4342.1432 cm-1) strong
      component, and the second of one parallel (nu0 = 4405.789 cm-1) and one
      perpendicular (nu0 = 4416.233 cm-1) weak component. The rovibrational analysis
      shows strong local perturbations for both strong and weak systems. Seven hundred
      eighty-one nonzero-weighted transitions belonging to the strong system [the (200)
      manifold in the local mode picture] were fitted to a simple model involving a
      perpendicular component interacting by a weak Coriolis resonance with a parallel
      component. The most severely perturbed transitions (whose ||obs-calc || values
      exceeded 3 x 10(-3) cm-1) were given zero weights. The standard deviations of the
      fit were 1.0 x 10(-3) and 0.69 x 10(-3) cm-1 for the parallel and the
      perpendicular components, respectively. The weak band system, severely perturbed
      by many "dark" perturbers, was fitted to a model involving one parallel and one
      perpendicular band, connected by a Coriolis-type resonance. The K" . DeltaK = +10
      to +18 subbands of the perpendicular component, which showed very high observed -
      calculated values ( approximately 0.5 cm-1), were excluded from this calculation.
      The standard deviations of the fit were 11 x 10(-3) and 13 x 10(-3) cm-1 for the
      parallel and the perpendicular components, respectively. Copyright 1998 Academic
      Press.

PMID- 9770389
TI  - REMPI Spectroscopy of SO Singlet States.
AB  - Three newly found vibrational levels at energies Te(v) = 45127.88(3),
      51900.40(4), and 52604.95(3) cm-1 allow the first application of resonance
      enhanced multiphoton ionization for detecting the SO radical in its low-energy
      singlet states, a1Delta and b1Sigma+. The analysis of the spectra is based on the
      observation of 10 rotationally resolved bands starting from a1Delta v = 0, 6
      ellipsis 11 and b1Sigma+ v = 8, covering a typical range of J = 5 ellipsis 40 or
      50. Population of these SO singlet states has been achieved by two-photon
      dissociation of SO2 in a molecular beam environment, applying wavelengths in the
      248 to 291 nm range. This paper presents an analysis of the rotational,
      vibrational, and electronic properties of the new levels. Reviewing earlier works
      on the singlet states of SO, a revised term energy scheme is provided which
      connects the singlet and triplet systems of the molecule. Copyright 1998 Academic
      Press.

PMID- 9770388
TI  - Circular Dichroism at Microwave Frequencies: Calculated Rotational Strengths for
      Transitions Up to J = 10 for Some Oxirane Derivatives.
AB  - Calculated dipole strengths and rotational strengths for microwave transitions in
      the range of 3-26 GHz are presented for six chiral small molecules. The molecules
      are the three chiral deuterated oxiranes, methyloxirane, trans-dimethyloxirane,
      and methylthiirane. Transitions which appear to be the best candidates for
      observation of circular dichroism in the microwave are identified. Copyright 1998
      Academic Press.

PMID- 9770390
TI  - High-Resolution Microwave and Infrared Molecular-Beam Studies of the Conformers
      of 1,1,2,2-Tetrafluoroethane.
AB  - High-resolution microwave and infrared molecular-beam spectra have been measured
      for 1,1,2,2-tetrafluoroethane (HFC134). For the higher energy, polar, C2
      symmetry, gauche conformer, microwave spectra have been recorded for the normal
      and mono-13C isotopomers and analyzed to determine a C-C bond length of 1.512(4)
      A, in good agreement with a recent ab initio value (MP2/6-31G**) of 1.515 A [S.
      Papasavva, K. H. Illinger, and J. E. Kenny, J. Phys. Chem. 100, 10100-10110
      (1996)]. A tunable microwave-sideband CO2 laser and electric-resonance
      optothermal spectrometer have been used to measure the infrared spectrum of the
      nu6, C-C stretch of the gauche conformer near 906 cm-1. Microwave-infrared double
      resonance and precise ground state combination differences provided by the
      microwave measurements guide the assignment of the spectrum. The observation of a
      c-type spectrum definitively establishes that the upper state vibration is of A
      symmetry in the C2 point group. The spectrum is fit to a Watson asymmetric-top
      Hamiltonian to a standard deviation of 0.24 MHz. A weak perturbation shifts the
      line positions for transitions near J = Kc = 20 by as much as 12 MHz. The
      identity of the perturber is unknown. Pulsed slit-jet diode-laser spectra have
      been recorded for the nu16 vibration of the anti conformer near 1127 cm-1. An a-
      and c-type hybrid band is observed, consistent with a Bu symmetry mode. Previous
      low-resolution studies have attributed the 1127-cm-1 mode to either a Bu or an Au
      symmetry vibration. A total of 522 nonblended transitions were assigned and fit
      to determine ground and excited state constants. The ground state constants of A
      = 5134.952(65) MHz, B = 3148.277(27) MHz, and C = 2067.106(43) MHz are the first
      experimental determinations of the rotational constants for this conformer. Here,
      type A standard uncertainties are given in the parentheses. Copyright 1998
      Academic Press.

PMID- 9770391
TI  - Ab Initio MRCI Calculation and Modeling of the A1Pi Potential Energy Curve of CO.
AB  - We report a MRCI study of the A1Pi potential energy curve of CO. The calculated
      ab initio energies are analytically modeled using the EHFACE2 and RKHS methods. A
      barrier of approximately 730 cm-1 is predicted at an internuclear distance of
      approximately 4.2a0 in agreement with previous calculations and spectroscopic
      measurements. The origin of such a barrier is briefly discussed. Copyright 1998
      Academic Press.

PMID- 9770393
TI  - The 2nu1 + nu2 + 3nu3 Band of 16O3: Line Positions and Intensities.
AB  - The 2nu1 + nu2 + 3nu3 band of ozone, which occurs in the 5700-cm-1 region, has
      been observed for the first time using a Fourier Transform Spectrometer,
      operating at 0.008 cm-1 resolution and with a large pathlength x pressure product
      (3216 cm x 28.3 Torr). The assignment of rotation-vibration transitions has been
      done for J up to 38 and Ka up to 11, respectively, after many difficulties due to
      a Coriolis coupling between (213) and (420) states. In this work we show how this
      one, which occurs between closed band centers (4 cm-1) but corresponds to
      summation operatoriDelta vi = 6, strongly perturbs energy levels and leads to a
      difficulty in assignments. In particular we show the deviations for various types
      of J and Ka as large as 1 cm-1, with respect to the calculations performed
      without account of this resonance. The final calculation for the 212
      rovibrational states is very satisfactory, as the r.m.s. is 2.5 x 10(-3) cm-1,
      near the experimental accuracy, with meaningful spectroscopic Hamiltonian
      parameters. Rovibrational lines intensities of the 2nu1 + nu2 + 3nu3 band were
      measured, and the value of the transition moment has been recovered. Finally a
      complete list of line positions and intensities was calculated (with a cut-off of
      3 x 10(-26) cm-1/molecule cm-1) leading to a total band intensity of Sv = 3.118
      10(-23) cm-1/molecule cm-2 at 296 K. Copyright 1998 Academic Press.

PMID- 9770392
TI  - Fourier Transform Spectroscopy of Carbonyl Sulfide from 3700 to 4800 cm-1 and
      Selection of a Line-Pointing Program.
AB  - We have measured the Fourier transform spectrum of natural OCS from 3700 to 4800
      cm-1 with a near Doppler resolution and a line-position accuracy between 4 and 8
      x 10(-5) cm-1. For the normal isotopic species, 37 vibrational transitions have
      been analyzed for both frequencies and intensities. We also report 15 bands of
      OC34S, eight bands of O13CS, nine bands of OC33S, and two bands of 18OCS.
      Important effective Herman-Wallis terms are explained on the basis of
      eigenvectors. A comparison of different line-pointing programs is also presented.
      Copyright 1998 Academic Press.

PMID- 9770394
TI  - LIF Studies of the A1A' States of BiOH and BiOD.
AB  - Electronic spectra of the recently discovered BiOH and BiOD radicals have been
      studied by means of laser-induced fluorescence measurements in the 400-1000 nm
      range. Laser excitation spectra observed in the range 430-450 nm are attributed
      to transitions from the &Xtilde;1A' ground state to the theoretically predicted
      A1A' state. Fluorescence spectra from the A1A',nu'3 = 0, 1 levels consist of
      short nu"3 progressions to the lower states &Xtilde;1A', &Xtilde;3A', and a1A'.
      Laser excitation spectra in the range 580-620 nm contain bands with both DeltaKa
      = 0 and DeltaKa = +/-1 subbands. They are attributed to hybrid bands of the A1A'
      <-- &Xtilde;3A' transition. Analyses of the spectra have yielded vibronic energy
      levels of the &Xtilde;1A', &Xtilde;3A', a1A', and A1A' states of both isotopes
      and effective rotational constants A - 1/2(B + C) and DK for some levels. The
      radiative lifetime of the A1A',000 state was found to be 0.92 +/- 0.03 us.
      Copyright 1998 Academic Press.

PMID- 9770395
TI  - Torsional Splittings in the Band nu9 + nu4 - nu4 of Ethane.
AB  - Torsional splittings of the C2H6 hot band nu9 + nu4 - nu4 have been determined
      based on measurements taken with the Kitt Peak National Observatory Fourier
      transform spectrometer with .0025 cm-1 resolution. The measured splittings range
      from -.2347 cm-1 (the sign is relative to that of the observed splitting in the
      nu9 band of C2H6) to .0682 cm-1, with a standard deviation of the observed
      splittings of .0251 cm-1. The splittings can be explained as a result of xy
      Coriolis interaction of nu9 + nu4 with the excited torsional states taunu4, with
      the major effect arising from the "forbidden" interaction with the nearly
      degenerate state 5nu4final sigma = 2. The rms error of the predicted splittings
      is .00422 cm-1, if parameters determined from theory and previous work are used,
      and is .00217 cm-1, if small refinements to the parameters are made based on the
      measured splittings themselves. Copyright 1998 Academic Press.

PMID- 9770396
TI  - Gas Phase LIF Study of the b1Sigma+(b0(+)) left and right arrow X3Sigma-(X10(+),
      X21) Transition of NI.
AB  - First gas phase spectra of the nitrogen monoiodide radical NI are reported. The
      b1Sigma+(b0(+)) left and right arrow X3Sigma-(X10(+), X21) transition of NI has
      been studied by laser-induced fluorescence measurements. Ground state NI radicals
      were generated in a fast-flow system by reaction of microwave-discharged nitrogen
      with iodine vapor. Vibrational levels v = 0, 1, and 2 of the b1Sigma+ state were
      excited with a pulsed dye laser. Rotational and vibrational constants of the
      X3Sigma- and b1Sigma+ states were deduced from analysis of high-resolution
      excitation spectra. Time-resolved measurements of the fluorescence decay and
      measurements of relative line and band intensities allowed determination of the
      radiative lifetime of the b state, of band transition probabilities, and of the
      ratio of transition moments u0/u1 for the b0(+) --> X10(+) and b0(+) --> X21
      subtransitions. Comparison of calculated and experimental line intensities and FC
      factors shows that treatment of the X3Sigma- state in terms of a Hund's case (a)
      formalism is preferable to use of a case (c) formalism. Copyright 1998 Academic
      Press.

PMID- 9770397
TI  - Microwave Spectrum and Barrier to Internal Rotation in ortho-Tolunitrile.
AB  - The microwave rotational spectra of ortho-tolunitrile (C6H4CH3CN) have been
      investigated in the ground torsional state in the frequency ranges of 22.0-26.0
      GHz and 32.0-37.0 GHz. The true rotational constants were determined to be Ar =
      2890.98 MHz, Br = 1499.75 MHz, and Cr = 993.58 MHz. A least-squares analysis of
      the A - E splittings of 16 transitions resulted in the values of V3 = 533.53
      cal/mol and thetaa = 54.22 degrees, assuming V6 = 0 and Ialpha = 3.2 a.m.u. A2.
      Copyright 1998 Academic Press.

PMID- 9770398
TI  - Infrared and Microwave Spectra and Force Field of DBO: The Coriolis Interaction
      between the nu1 and nu2 + nu3 States.
AB  - The nu1 and nu3 bands of D11BO and the nu1 band of D10BO were observed by using
      an infrared diode laser spectrometer. The DBO molecule was generated by an ac
      discharge in a mixture of BCl3, D2, O2, and He. As inferred previously, a strong
      Coriolis interaction was in fact found to take place between the nu1 and nu2 +
      nu3 states, and an analysis of the observed nu1 spectra, which explicitly took
      into account this Coriolis interaction, predicted the pure rotational transition
      frequencies of DBO in the nu1 state. Pure rotational lines were then detected by
      microwave spectroscopy, confirming the validity of the infrared assignment. In
      the microwave experiment DBO molecules were generated by a discharge in a mixture
      of B2D6 and O2. The three fundamental bands and a hot band of D11BO, as well as
      the nu1 and nu3 bands of D10BO, were subsequently recorded in emission with a
      Fourier transform infrared spectrometer. DBO molecules were generated by the
      reaction of D2 with HBO at temperatures above 800 degreesC in a ceramic tube
      furnace. All of the observed spectra were simultaneously subjected to a least
      squares analysis to obtain molecular parameters in the ground, nu1, nu2, nu3, and
      nu2 + nu3 states. The results thus obtained improved the force field and
      molecular structure of the HBO/DBO molecules reported in a previous study (Y.
      Kawashima, Y. Endo, and E. Hirota, 1989, J. Mol. Spectrosc. 133, 116-127).
      Copyright 1998 Academic Press.

PMID- 9770399
TI  - Cavity-Ring-Down Spectroscopy on the b1Sigma+g-X3Sigma-g (1,0) Band of Oxygen
      Isotopomers.
AB  - The b1Sigma+g-X3Sigma-g (1,0) band of 16O17O, 16O18O, 18O2, 17O18O, and 17O2
      isotopomers was investigated employing the technique of cavity-ring-down
      spectroscopy. More than 400 transition frequencies of magnetic dipole lines were
      determined with a typical uncertainty of 0.01 cm-1. This work results in new or
      improved accurate molecular constants for the excited b1Sigma+g, v = 1 state of
      all isotopomers and for the X3Sigma-g, v = 0 ground state of 17O2. Copyright 1998
      Academic Press.

PMID- 9770401
TI  - Vibrational Structure of the (2)1Sigma+u-X(1)1Sigma+g Transition of the Ba2
      Molecule.
AB  - Resonant two photon ionization (R2PI) technique was used to obtain the excitation
      spectrum of the Ba2 molecule. A group of 12 vibrational bands was found in the
      740-764 nm region. As a result of mass selective detection, they were attributed
      unambiguously to the Ba2 molecule. By comparison to recent theoretical
      calculations, those bands were assigned to the (2)1Sigma+u-X(1)1Sigma+g
      transition; they may be fitted to give the following vibrational constants (in cm
      1): omega"e = 33.2 +/- 0.2, omega"ex"e = 0.5 +/- 0.2, omegae = 65.2 +/- 0.2, and
      omega'ex'e = 0.4 +/- 0.2. Copyright 1998 Academic Press.

PMID- 9770400
TI  - Double Resonance Sub-Doppler Study of the Allowed and DeltaK = -3 Forbidden Q(3,
      3) Transitions to the nu2 Vibrational State of 14NH3.
AB  - The IR-IR sub-Doppler double resonance and standard saturation sideband
      spectroscopy have been used to measure the allowed and Deltak = -3 forbidden
      transitions to the nu2 vibrational level of 14NH3. The IR-IR double resonance
      technique has made it possible to observe quadrupole hyperfine structures which
      correspond to the sums as well as differences of the -3Q(3, 3) and Q(3, 3)
      hyperfine components. The "sum" and "difference" double resonance frequencies
      have been measured with accuracy better than 30 and 5 kHz, respectively. In
      addition to this, the hyperfine structure of the allowed Q(3, 3) transition has
      been independently measured using the "standard" saturation sideband spectroscopy
      with accuracy better than 15 kHz. A simultaneous analysis of all measured data
      provides an improved set of effective nuclear quadrupole and spin-rotation
      parameters for the excited nu2 vibrational state and frequencies of the "pure"
      rotation-vibration transitions deperturbed from the hyperfine effects at the
      experimental sample pressure of about 3 mTorr, including a very precise zero
      pressure value of the "forbidden" spacing between energies of the nu2 ||s, J = 3,
      K = 3> and ||s, J = 3, K = 0> pure rotational levels of 2883.6795(19) MHz
      [0.096189194(63) cm-1]. Copyright 1998 Academic Press.

PMID- 9770402
TI  - Far-Infrared Laser Sideband Spectroscopy of the NH2 Radical.
AB  - We have constructed a far-infrared (FIR) laser sideband spectrometer for carrying
      out pure rotational spectroscopy of fundamental radicals and ions in the FIR or
      "terahertz" frequency region. The tunable FIR source is obtained by sideband
      generation of a carbon dioxide laser-pumped FIR laser with a GaAs Schottky
      barrier diode. The minimum detectable absorption coefficient of the spectrometer
      achieved so far is 1 x 10(-6) cm-1 at 1600 GHz. Observation of the pure
      rotational spectrum of the NH2 radical in the 2B1 ground electronic state was
      demonstrated as the first example. Spectra were measured by utilizing the double
      modulation technique; i.e., the Zeeman effect was used in addition to the normal
      frequency modulation technique in order to flatten the baseline and to appreciate
      full system sensitivity. The radical was generated by a DC glow discharge of a
      mixture of ammonia and helium. Nine Q- and R-branch rotational transitions were
      measured in the frequency range between 1300 and 2600 GHz. Zero-field transition
      frequencies were obtained with an accuracy of around 1 MHz. The line frequencies
      were analyzed with previous microwave spectroscopic results, and the rotational
      and spin-rotation constants with their centrifugal correction terms were revised.
      With the aid of the revised rotational constants, it becomes possible to predict
      the line frequency of certain low N transitions of the radical to within about 1
      MHz for the first time. Copyright 1998 Academic Press.

PMID- 9770404
TI  - On the Singlet Spectrum of ZrS.
AB  - Three electronic transitions in the singlet manifold of the zirconium sulphide
      (ZrS) molecule have been rotationally analyzed. They are the B1Pi-X1Sigma+,
      C1Sigma+-X1Sigma+, and E1Sigma+-X1Sigma+ systems with (0,0) band heads at 924.60,
      731.51, and 494.47 nm, respectively. The ground state X1Sigma+ has an equilibrium
      bond distance of 2.15661(4) A. Perturbations in the B1Pi and C1Sigma+ states are
      discussed. Copyright 1998 Academic Press.

PMID- 9770403
TI  - New Assignments in the Green and Red Band Systems of the FeH Radical.
AB  - The electronic spectrum of FeH in the regions of the 532 nm (green) and 630 nm
      (red) systems has been investigated using the techniques of dispersed and
      undispersed laser induced fluorescence. Sixteen lines have been assigned in the
      Omega = 1/2 <-- Omega = -1/2 subband of the e6Pi-c6Sigma+ transition and term
      values determined for the previously uncharacterized e6Pi1/2 spin-orbit
      component. A further fourteen lines were assigned to the connected Omega = 1/2 <-
      Omega = 3/2 subband of the e6Pi-a6Delta transition and term values for the
      hitherto uncharacterized a6Delta3/2 component were determined. A study of the
      high-temperature spectrum of FeH, recorded previously by McCormack and O'Connor
      (1), enabled the branches of the Omega = 7/2 <-- Omega = 9/2 subband of the e6Pi
      a6Delta transition to be extended to higher J values. These predictions were
      confirmed by laser induced fluorescence (LIF) experiments and led to the
      assignment of 13 additional lines in this subband. The term values for the
      e6Pi7/2 and a6Delta9/2 spin-orbit components were thus extended to higher J
      values. Copyright 1998 Academic Press.

PMID- 9770406
TI  - Simultaneous Rovibrational Analysis of the nu2, nu3, nu5, and nu6 Bands of
      H313CF.
AB  - A total of 6071 transition wavenumbers of the nu2, nu3, nu5, and nu6 fundamental
      bands of H313CF and 1689 frequencies of the rotational transitions in the v2 = 1,
      v3 = 1, v5 = 1, and v6 = 1 vibrational states have been fitted simultaneously by
      taking into account various Coriolis interactions, l-type interactions, and alpha
      resonance terms between and within the vibrational states. The standard deviation
      of the fit using 75 parameters was final sigma = 7.63 x 10(-5) cm-1 for the
      infrared data and 0.150 MHz for the rotational data. The possibility of obtaining
      a quantitative fit of the very precise data of high-resolution Fourier transform
      and submillimeter-wave spectroscopy for a semirigid symmetric top molecule is
      discussed. Copyright 1998 Academic Press.

PMID- 9770405
TI  - The NO Vibrational Fundamental Band: O2-Broadening Coefficients.
AB  - The first measurements of O2 broadening of NO lines is reported. For the NO
      fundamental vibration-rotation band, polynomial representations for this
      broadening at 299 K are given for Omega = 32 and Omega = (1/2) e and f
      transitions, respectively: gamma3/2(|m|) = 0.06463 - 0.00262|m| + 0.000147|m|2 -
      0.00000327|m|3, gammaf1/2 (|m|) = 0.06515 - 0.00381|m| + 0.000271|m|2 -
      0.00000665|m|3, and gammae1/2(|m|) = 0.06433 - 0.00343|m| + 0.000214|m|2 -
      0.00000497|m|3. These broadening coefficients are on the order of 17% smaller
      than the comparable coefficients found for N2 broadening of NO. Copyright 1998
      Academic Press.

PMID- 9770407
TI  - Microwave Spectrum of the SD+3 Ion: Molecular Structure.
AB  - The J = 1-0 to 4-3 spectral lines of SD+3 were measured in the 152-610 GHz region
      using a source-modulated microwave spectrometer. The SD+3 ion was generated in a
      free space absorption cell by a hollow-cathode discharge in a gas mixture of D2S
      and D2. The rotational constant B0 and the centrifugal distortion constants DJ
      and DJK were determined from the measured frequencies. A vibration-rotation
      analysis was carried out and the rz structures of SH+3 and SD+3 were derived from
      their zero point averaged rotational constants, expressed as SH+3: rz =
      1.36512(22) A and thetaz = 94.098(26) degrees, and SD+3: rz = 1.36086(16) A and
      thetaz = 94.1211(195) degrees, where the difference between thetaz(HSH) and
      thetaz(DSD) was assumed to be the same as that between thetaz(HPH) of PH3 and
      thetaz(DPD) of PD3. From the shift between the rz structures of SH+3 and SD+3,
      the re structure of SH+3 was estimated to be re = 1.35001(113) A, thetae =
      94.181(135) degrees. Copyright 1998 Academic Press.

PMID- 9770408
TI  - Collisional-Broadening Coefficients in the nu6 Band of 12CH3F Perturbed by Ar.
AB  - Ar-broadening coefficients are measured for 29 lines of CH3F in the RQ0 and RQ6
      branches of the nu6 band, using a tunable diode-laser spectrometer. The
      collisional widths obtained by fitting Rautian profiles to the measured shapes of
      the lines are significantly larger, especially for the overlapping lines at low-J
      values, than those obtained from Voigt profiles. The broadening coefficients for
      the lines belonging to the same low-J transitions (J = 7-10) appear to be greater
      in the RQ0 branch than in the RQ6 branch. Comparisons have been made with
      calculated results based on a semiclassical model including adjustable potential
      parameters. Copyright 1998 Academic Press.

PMID- 9770409
TI  - Color Center Laser Infrared Absorption Spectroscopy of the nu12 Band of Benzene
      Cooled in a Pulsed Jet.

PMID- 9770410
TI  - Where Is the Intensity Maximum in a Pure Rotational Spectrum?

PMID- 9770412
TI  - Novel Intracavity Jet Millimeter Wave Spectrometer: Detection of b-Type
      Rotational Transitions of Ne-CO.

PMID- 9770411
TI  - An Analytical Formula for the Energy of the Bound Long-Range 0(-)g((1)3Pig) State
      of Cs2.

PMID- 9770414
TI  - Hepatitis C virus E1 protein induces modification of membrane permeability in E.
      coli cells.
AB  - The E1 gene of hepatitis C virus (HCV) has been cloned and expressed in
      BL21(DE3)pLys Escherichia coli strain by pET3a vector to analyze changes in
      membrane permeability produced by this protein. We showed that the expression of
      E1 (aa 192-383), as well as of two C-terminal fragments (aa 331-383 and aa 341
      383) corresponding to the transmembrane (TM) region of this protein, induced a
      rapid lysis of cells. On the contrary, the expression of a mutant of E1 (aa 192
      340), lacking the last 40 amino acids, did not cause cell lysis. The analysis of
      permeability changes revealed that modification of membrane permeability to
      several compounds were observed only in clones expressing E1 and C-terminal
      fragments, while the synthesis of the C-terminal-deleted mutant had little or no
      effect on permeability. These findings demonstrate that the TM domain of E1
      protein has membrane-active properties that may be involved in some aspects of
      virus-cell interaction.

PMID- 9770415
TI  - A classical bipartite nuclear localization signal on Thogoto and influenza A
      virus nucleoproteins.
AB  - We have previously shown that the nucleoprotein (NP) of Thogoto virus (THOV), a
      tick-borne member of the Orthomyxoviridae family, accumulates in the cell
      nucleus. Here we demonstrate that THOV NP contains a motif (KRxxxxxxxxxKTKK) at
      amino acid positions 179-193 that represents a classical bipartite nuclear
      localization signal (NLS). This sequence motif (named cNLS) was able to
      translocate a cytoplasmic 80-kDa reporter protein into the nucleus. Targeted
      mutations substituting lysines for alanines in the downstream cluster of the
      bipartite motif abolished the capacity of cNLS to mediate nuclear import. In
      contrast, identical mutations had no effect on nuclear localization when
      introduced into THOV NP, indicating that additional transport signals are present
      in NP. Amino-acid sequence comparisons revealed that THOV NP lacks the N-terminal
      nonconvential NLS (named here nNLS), which has been implicated in nuclear import
      of influenza A virus NP. Accordingly, THOV NP failed to interact in
      coprecipitation assays with the cellular NPI-1/3 transport factors of the
      karyopherin alpha family. A highly conserved motif identified in THOV NP was the
      so-called nuclear accumulation sequence (NAS). Mutating NAS alone, or in
      combination with cNLS, had no gross effect on the intracellular distribution of
      the protein, indicating that a functional NAS is not required for nuclear
      accumulation of THOV NP in mammalian cells. We also studied nuclear transport of
      influenza A/PR/8/34 virus NP. Interestingly, we found a cNLS motif at amino acid
      positions 198-216 in addition to the previously described nonconventional nNLS.
      To further assess the functional role of cNLS, nNLS, and NAS, we analyzed single,
      double, and triple mutants of influenza A virus NP. When nNLS was destroyed, the
      protein stayed in the cytoplasm as expected. When NAS was disrupted in addition
      to nNLS, the double mutant accumulated in the nucleus, suggesting that cNLS was
      active. Indeed, when cNLS was also inactivated, the triple mutant protein
      localized again predominantly to the cytoplasm. These findings suggest that NP of
      orthomyxoviruses have two independent NLSs, namely cNLS and nNLS. They further
      suggest that NAS and NLSs may assume opposing roles in nucleocytoplasmic
      transport of NP.

PMID- 9770416
TI  - Human papillomavirus oncoproteins alter differentiation-dependent cell cycle exit
      on suspension in semisolid medium.
AB  - The suspension of keratinocytes containing episomal forms of the human
      papillomavirus (HPV)-31 genome in semisolid medium results in the induction of
      viral late functions. In this study, the suspension in semisolid medium was used
      to analyze how HPV deregulates the process of cell cycle exit during
      differentiation. In cells that contain the entire HPV-31 genome, induction of
      late protein synthesis was found to be linked with the expression of cyclin A.
      Consistent with analyses in organotypic rafts, the expression of the high-risk E7
      oncoprotein alone was sufficient to retain cyclin A expression during suspension
      induced differentiation. The cyclin-dependent kinase inhibitors (CKIs) p27 and
      p57 were found to be up-regulated in normal keratinocytes, as well as in the
      lines that express the HPV oncoproteins. The up-regulation of these CKIs is
      coincident with the inhibition of cyclin/cdk activity in normal keratinocytes.
      Cells expressing E7 were found to retain significant cdk2-associated kinase
      activity, although it was partially inhibited, coincident with CKI induction.
      When the phosphorylation state of Rb was examined during differentiation, cells
      expressing E7 retained phosphorylated forms of Rb, whereas Rb in normal
      keratinocytes was hypophosphorylated. As previously reported, E7-expressing cells
      were found to contain less Rb protein than normal keratinocytes. Interestingly,
      the Rb levels decreased during normal keratinocyte differentiation, and this
      differentiation-dependent reduction in Rb levels was enhanced by EG and E7
      expression. This study identified proteins that may be critical for cell cycle
      regulation during normal epithelial differentiation and demonstrated that HPV
      oncoproteins alter their activities.

PMID- 9770418
TI  - Coronavirus MHV-3-induced apoptosis in macrophages.
AB  - Infection with mouse hepatitis virus strain 3 (MHV-3) results in lethal fulminant
      hepatic necrosis in fully susceptible BALB/c mice compared to the minimal disease
      observed in resistant strain A/J mice. Macrophages play a central role in the
      pathogenesis of MHV-3-induced hepatitis. In the present study we have shown that
      MHV-3 infection of macrophages induces these cells to undergo apoptosis. Three
      methods to detect apoptosis were applied: flow cytometry analysis of nuclear DNA
      content, fluorescence microscopic visualization of apoptotic cells labeled by the
      TUNEL assay, and gel electrophoresis to detect DNA laddering. Apoptosis in A/J
      and BALB/c macrophages was first detected at 8 h postinfection (p.i.) and reached
      a maximum by 12 h p.i. The degree of MHV-3-induced apoptosis was much greater in
      A/J-derived macrophages than in BALB/c-derived cells. Apoptosis was inversely
      correlated with the development of typical MHV cytopathology, namely syncytia
      formation. Infected macrophages from A/J mice did not form synctia in contrast to
      the extensive synctia formation observed in BALB/c-derived macrophages. In MHV-3
      infected BALB/c macrophage cultures, apoptotic cells were not incorporated into
      syncytia. Apoptosis was also inversely correlated with the expression of MHV-3
      induced fgl2 prothrombinase in macrophages. These results add the murine
      coronavirus MHV-3 to the list of RNA-containing viruses capable of inducing
      apoptosis.

PMID- 9770417
TI  - The paramyxovirus SV5 small hydrophobic (SH) protein is not essential for virus
      growth in tissue culture cells.
AB  - The SH gene of the paramyxovirus SV5 is located between the genes for the
      glycoproteins, fusion protein (F) and hemagglutinin-neuraminidase (HN), and the
      SH gene encodes a small 44-residue hydrophobic integral membrane protein (SH).
      The SH protein is expressed in SV5-infected cells and is oriented in membranes
      with its N terminus in the cytoplasm. To study the function of the SH protein in
      the SV5 virus life cycle, the SH gene was deleted from the infectious cDNA clone
      of the SV5 genome. By using the recently developed reverse genetics system for
      SV5, it was found that an SH-deleted SV5 (rSV5DeltaSH) could be recovered,
      indicating the SH protein was not essential for virus viability in tissue
      culture. Analysis of properties of rSV5DeltaSH indicated that lack of expression
      of SH protein did not alter the expression level of the other virus proteins, the
      subcellular localization of F and HN, or fusion competency as measured by lipid
      mixing assays and a new content mixing assay that did not require the use of
      vaccinia virus. The growth rate, infectivity, and plaque size of rSV5 and
      rSV5DeltaSH were found to be very similar. Although SH is shown to be a component
      of purified virions by immunoblotting, examination of purified rSV5DeltaSH by
      electron microscopy did not show an altered morphology from SV5. Thus in tissue
      culture cells the lack of the SV5 SH protein does not confer a recognizable
      phenotype.

PMID- 9770419
TI  - Sequence element required for efficient -1 ribosomal frameshifting in red clover
      necrotic mosaic dianthovirus.
AB  - The RNA-1 of the bipartite red clover necrotic mosaic dianthovirus (RCNMV) genome
      encodes the 88-kDa polymerase. The polymerase is translated from both 5' proximal
      and internal open reading frames by a -1 ribosomal frameshifting event. A shifty
      heptanucleotide conforming to the simultaneous slippage model is identified, and
      a downstream stem-loop structure and atypical pseudoknot are predicted. A beta
      glucuronidase reporter assay identified a 118-nucleotide element containing both
      the shifty heptanucleotide and the predicted secondary structures that were
      required for efficient -1 ribosomal frameshift expression in vivo. A series of
      site-directed and compensatory mutations affecting the base-paired regions of the
      predicted secondary structure were introduced into a RCNMV RNA-1 cDNA clone from
      which infectious transcripts were derived. Mutations that destroyed the predicted
      pseudoknot had no effect on frameshifting efficiency in vitro or infectivity of
      the virus, whereas mutations destabilizing the stem-loop structure abolished both
      ribosomal frameshifting in vitro and biological activity. These results
      demonstrate the essential role of a predicted secondary structure that does not
      involve a pseudoknot in the expression of the RCNMV polymerase by ribosomal
      frameshifting.

PMID- 9770420
TI  - Relationship between anti-Tax antibody responses and cocultivatable virus in HTLV
      I-infected rabbits.
AB  - The presence of anti-Tax antibody responses in human T cell leukemia virus type I
      (HTLV-I)-infected individuals has been correlated with increased proviral load,
      increased risk of transmitting infection, and increased risk of developing
      tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). In this
      study, a rabbit model of HTLV-I infection was used to determine whether anti-Tax
      antibody responses could predict the presence of virus with the potential to
      replicate. Seven of 14 HTLV-I-infected rabbits developed anti-Tax antibody
      responses. The onset of Tax reactivity was variable, but once detected remained
      constant throughout the remainder of the 60-week course of the study. All anti
      Tax antibody positive rabbits produced virus as measured by p19 expression upon
      coculture, while p19 was detected in only one of the Tax antibody negative
      animals. Thus the presence of an anti-Tax antibody response correlates with p19
      expression following cocultivation, and may be a useful predictor of virus
      replication in HTLV-I infected individuals.

PMID- 9770422
TI  - Apoptosis precedes necrosis of fish cell line with infectious pancreatic necrosis
      virus infection.
AB  - The current view of infectious pancreatic necrosis virus (IPNV) infection
      includes a necrotic process that relies primarily on the histological appearance
      of tissue after the degenerative process. We tested this view by examining the
      possibility that apoptosis is a component of double-stranded RNA virus (IPNV)
      that induces fish embryonic cell death. Four kinds of assays for apoptosis were
      used in analyzing IPNV-infected CHSE-214 cells: (1) assay with terminal
      deoxynucleotidyl transferase (TdT)-mediated end-labeling of DNA in nuclei of
      intact cells during virus infection, (2) assay for procoagulant activity, (3)
      assay for DNA ladders, and (4) electron microscopic assays for the
      ultrastructural changes in characteristic apoptotic cells. In all p.i. samples,
      both low and high m.o.i. groups contained apoptotic nuclei, according to TdT
      mediated dUTP labeling of intact cells, but in control CHSE-214 cells, apoptotic
      nuclei were rare at all levels of incubation sampled by TdT-mediated dUTP
      labeling. Prenecrotic or postnecrotic cells were found to express
      phosphatidylserine on the surface by annexin V-FITC labeling, but normal cells
      did not. DNAs from both 4 h p.i. of high m.o.i. and 8 h p.i. of low m.o.i. were
      found to be cleaved into fragments indicative of preferential cleavage at
      internucleosomal sites. The IPNV-infected CHSE-214 cells were analyzed with an
      electron microscope and showed a pattern of ultrastructural change, indicating
      that apoptosis appears before pathological changes of necrosis, including
      condensed chromatin, fragmented nuclei, nuclei with chromatin marginations, and
      secondary necrosis from prenecrotic cells in IPNV-infected CHSE-214 cells.
      Together, these findings show that apoptosis precedes any detectable necrotic
      change in CHSE-214 cells that is currently viewed as necrosis. Thus, apoptosis
      characterizes the onset of pathology in host cells and is followed by necrotic
      processes.

PMID- 9770421
TI  - Retrograde transport of intact poliovirus through the axon via the fast transport
      system.
AB  - Intramuscularly inoculated poliovirus is thought to spread to the central nervous
      system through neural pathways in humans, monkeys, and the transgenic (Tg) mice
      carrying the human poliovirus receptor (PVR) gene. To gain insight into molecular
      mechanisms for the retrograde axonal transport of poliovirus, resulting in the
      expression of neurovirulence, a poliovirus-sensitive ICR-PVRTg21 mouse line
      (Tg21) was used as an animal model for poliomyelitis. We detected poliovirus
      antigens in axons of the sciatic nerve. All of the Tg21 mice, which had been
      inoculated into the calves with 1 x 10(6) pfu of the Mahoney strain of type 1
      poliovirus, showed symptoms of paralysis in the inoculated limbs (initial
      paralysis) within 48 h after the inoculation. The appearance of this initial
      paralysis was observed in mice whose sciatic nerves were transected at various
      times after virus inoculation. The results were indicators of the velocity of
      poliovirus transportation through the sciatic nerves under analysis. Poliovirus
      related materials recovered from the sciatic nerve were mainly composed of intact
      160S virion particles. The amount of 160S particle recovered was greatly reduced
      by coinjection with anti-PVR monoclonal antibody. These results suggest that one
      of the fast retrograde axonal transport systems is involved in poliovirus
      dissemination through the sciatic nerve and that IM-inoculated poliovirus is
      incorporated into the sciatic nerve as intact particles in a PVR-dependent
      manner, as it is in humans.

PMID- 9770423
TI  - Echovirus 1 infection induces both stress- and growth-activated mitogen-activated
      protein kinase pathways and regulates the transcription of cellular immediate
      early genes.
AB  - We have previously shown that echovirus 1 (EV1) infection increases the mRNA
      levels of cellular immediate-early (IE) genes in host cells. Here we provide
      further evidence that the induction of junB, c-jun, and c-fos genes is due to
      active viral macromolecular synthesis rather than to the interaction of EV1 with
      its receptor, alpha2beta1 integrin. Nuclear run-on transcription assays indicated
      that differences in mRNA levels in infected and uninfected cells are brought
      about by regulation at the transcriptional level. EV1 infection induced the
      phosphorylation of both the stress-related p38 mitogen-activated protein kinase
      (MAPK) and the growth signal-related ERK1/2 MAPKs. Studies with selective MAPK
      inhibitors revealed that p38 was the main inducer of junB expression, whereas
      both MAPK pathways were involved in the induction of c-fos. Activation of AP-1
      genes was also observed to occur during infections with other enteroviruses and
      with Semliki Forest A7(74) virus, suggesting that the phosphorylation of MAPKs
      and induction of AP-1 gene expression may be important regulators of host cell
      behavior during viral infections.

PMID- 9770424
TI  - Characterization of mRNA for hepatitis delta antigen: exclusion of the full
      length antigenomic RNA as an mRNA.
AB  - Hepatitis delta virus (HDV) encodes a single protein, the hepatitis delta antigen
      (HDAg), which is thought to be translated from a 0. 8-kb RNA of antigenomic
      sense. This subgenomic RNA species is present in very small amounts in HDV
      infected liver tissues and in cultured cells infected or transfected with HDV,
      and in some cases it cannot be detected at all. In contrast, HDAg protein is
      present in large amounts in all natural and experimental models of HDV infection.
      This study addresses whether other HDV RNA species, such as the antigenomic
      sense, genome-size HDV RNA can also serve as the mRNA for HDAg synthesis. Taking
      advantage of the ability of herpes simplex virus (HSV) to degrade only
      polyadenylated mRNAs, we examined the effect of HSV coinfection on HDAg
      synthesis. It was shown that HSV infection did degrade the subgenomic 0.8-kb HDV
      mRNA but not HDV genome-length RNA. Under such conditions, HDAg synthesis was
      completely inhibited. Furthermore, the genome-length HDV RNA was found not to be
      associated with polysomes. Finally, in vitro translation studies demonstrated
      that HDAg could not be translated directly from the genome-length antigenomic
      sense HDV RNA. These results suggest that only the subgenomic RNA species of HDV
      possesses properties characteristic of the mRNA for HDAg and that the genome
      length RNA cannot be used for translating HDAg. In addition, we found that HDV
      RNA replication did not depend on de novo HDAg synthesis.

PMID- 9770426
TI  - AcMNPV late expression factor-5 interacts with itself and contains a zinc ribbon
      domain that is required for maximal late transcription activity and is homologous
      to elongation factor TFIIS.
AB  - The late expression factor-5 gene (lef-5) of Autographa californica
      multinucleocapsid polyhedrovirus (AcMNPV) is required for late gene expression.
      In this paper, we demonstrate that LEF-5 interacts with itself in the yeast two
      hybrid system and in glutathione-S-transferase affinity assays. Deletion analysis
      suggested that the C-terminal 71 amino acids (aa) were not required for
      interaction. However, all deletions tested involving the N-terminal 194 aa
      significantly reduced LEF-5:LEF-5 interaction. LEF-5 or LEF-5 deletion mutants
      were transfected into Sf-9 cells with the full complement of genes required for
      baculovirus late transcription. All deletion clones tested reduced expression of
      a beta-glucuronidase (GUS) reporter gene under control of the late vp39 capsid
      promoter. Amino-acid sequence analysis of LEF-5 identified a previously
      unreported domain within the C-terminal 32 aa that is homologous to the zinc
      ribbon domain of RNA polymerase II elongation factor IIS (TFIIS) from a variety
      of taxa. Molecular modeling of the putative LEF-5 Zn ribbon using the NMR data
      available for the Zn ribbon of TFIIS suggested that this domain could fold into a
      Zn ribbon structure similar to TFIIS. Alanine scanning mutagenesis of amino acids
      predicted to be important for functioning of the LEF-5 ribbon structure
      significantly reduced LEF-5 activity in transient expression assays. Mutations
      changing the amino acids predicted to coordinate Zn2+ caused a reduction in
      activity similar to that when the domain was eliminated completely.

PMID- 9770425
TI  - Assaying for structural variation in the parvovirus capsid and its role in
      infection.
AB  - The capsid of canine parvovirus (CPV) was assayed for susceptibility to proteases
      and for structural variation. The natural cleavage of VP2 to VP3 in CPV full (DNA
      containing) particles recovered from tissue culture occurred within the sequence
      Arg-Asn-Glu-Arg Ala-Thr. Trypsin, chymotrypsin, bromelain, and cathepsin B all
      cleaved >90% of the VP2 to VP3 in full but not in empty capsids and did not
      digest the capsid further. Digestion with proteinase K, Pronase, papain, or
      subtilisin cleaved the VP2 to VP3 and also cleaved at additional internal sites,
      causing particle disintegration and protein degradation. Several partial
      digestion products produced by proteinase K or subtilisin were approximately 31
      32.5 kDa, indicating cleavage within loop 3 of the capsid protein as well as
      other sites. Protease treatment of capsids at pH 5.5 or 7.5 did not significantly
      alter their susceptibility to digestion. The isoelectric point of CPV empty
      capsids was pH 5.3, and full capsids were 0.3 pH more acidic, but after
      proteolysis of VP2 to VP3, the pI of the full capsids became the same as that of
      the empty capsids. Antibodies against various capsid protein sequences showed the
      amino termini of most VP2 molecules were on the outside of full but not empty
      particles, that the VP1-unique sequence was internal, and that the capsid could
      be disintegrated by heat or urea treatment to expose the internal sequences.
      Capsids added to cells were localized within the cell cytoplasm in vesicles that
      appeared to be lysosomes. Microinjected capsids remained primarily in the
      cytoplasm, although a small proportion was observed to be in the nucleus after 2
      h. After CPV capsids labeled with [35S]methionine were bound to cells at 0
      degrees C and the cells warmed, little cleavage of VP1 or VP2 was observed even
      after prolonged incubation. Inoculation of cells with virus in the presence of
      proteinase inhibitors did not significantly reduce the infection.

PMID- 9770427
TI  - Constitutive production of a murine retrovirus in the human B-lymphoblastoid cell
      line, DG-75.
AB  - During the screening of human lymphoblastoid cells as suitable hosts for
      retrovirus transmission studies, the Epstein-Barr virus (EBV)-negative, B
      lymphoblastoid cell line DG-75 was found to be chronically infected with a
      heretofore unrecognized retrovirus. Two DG-75 sublines obtained from different
      sources (designated UW and KAR) were found to produce constitutively particles
      identified as retroviral by electron microscopy and reverse transcriptase
      activity. The ultrastructure, morphogenesis, and density in sucrose of the
      particles were typical of C-type retroviruses. Immunoblot analysis of the DG
      75(UW) retrovirus proteins showed antigenic similarity to Moloney murine leukemia
      virus. A third DG-75 subline in early passage, designated HAD, was free of
      retrovirus. The DG-75(UW) retrovirus was infectious and produced progeny virions
      that could be passaged to uninfected cells. We have thus demonstrated that DG-75
      cells, which have been used extensively in studies of the biological effects of
      EBV-encoded genes and their promoters, may be chronically infected with a murine
      retrovirus and that an early passage subline is retrovirus free and available for
      such studies.

PMID- 9770428
TI  - A human liver cell line exhibits efficient translation of HCV RNAs produced by a
      recombinant adenovirus expressing T7 RNA polymerase.
AB  - An in vitro system that supports the efficient growth of hepatitis C virus (HCV)
      and reflects its complete in vitro replication cycle has not yet been
      established. The establishment of a minigene RNA of HCV in mammalian cells could
      facilitate the study of virus-cell interactions and the molecular pathogenesis of
      this virus. We constructed a replication-deficient recombinant adenovirus
      expressing bacteriophage T7 RNA polymerase under the control of CAG promoter
      (AdexCAT7). A high level of T7 RNA polymerase was detectable for at least 11 days
      after inoculation. Cells infected with AdexCAT7 were then transfected with
      plasmids carrying the authentic T7 promoter, the 5' untranslated region (UTR) of
      encephalomyocarditis virus, a luciferase gene, and a T7 terminator (pT7EMCVLuc)
      or carrying the modified T7 promoter, the 5'UTR of HCV, a luciferase gene, the
      coding region of C-terminal of NS5B and the 3'UTR of HCV, a ribozyme of hepatitis
      D virus and a T7 terminator (pT7HCVLuc). Most of the cell lines examined
      supported a higher expression of luciferase by transfection with pT7EMCVLuc than
      with pT7HCVLuc. However, one cell line, FLC4, derived from a human hepatocellular
      carcinoma, exhibited very high reporter gene expression with pT7HCVLuc. In this
      cell line, transfection with RNA synthesized in vitro from pT7HCVLuc induced a
      higher level of reporter gene expression than RNA from pT7EMCVLuc. The T7
      adenovirus system for the synthesis of HCV minigenes in vivo provides useful
      information on the molecular mechanisms of HCV translation in human liver cells.

PMID- 9770429
TI  - DNA-based and alphavirus-vectored immunisation with prM and E proteins elicits
      long-lived and protective immunity against the flavivirus, Murray Valley
      encephalitis virus.
AB  - The immunogenicity and protective efficacy of DNA-based vaccination with plasmids
      encoding the membrane proteins prM and E of the flavivirus Murray Valley
      encephalitis virus (MVE) were investigated. Gene gun-mediated intradermal
      delivery of DNA encoding the prM and E proteins elicited long-lived, virus
      neutralising antibody responses in three inbred strains of mice and provided
      protection from challenge with a high titer inoculum of MVE. Intramuscular DNA
      vaccination by needle injection also induced MVE-specific antibodies that
      conferred resistance to challenge with live virus but failed to reduce virus
      infectivity in vitro. The two routes of DNA-based vaccination with prM and E
      encoding plasmids resulted in humoral immunty with distinct IgG subtypes. MVE
      specific IgG1 antibodies were always prevalent after intradermal DNA vaccination
      via a gene gun but not detected when mice were immunised with DNA by the
      intramuscular route or infected with live virus. We also tested a Semliki Forest
      virus replicon as vector for a flavivirus prM and E protein-based subunit
      vaccine. Single-cycle infections in mice vaccinated with packaged recombinant
      replicon particles elicited durable, MVE-specific, and virus-neutralising
      antibody responses.

PMID- 9770430
TI  - Virulence markers in the 5' untranslated region of genotype 2 bovine viral
      diarrhea virus isolates.
AB  - Virulence markers to distinguish high from low virulence bovine viral diarrhea
      virus genotype 2 isolates have not been previously reported. The objective of
      this study was to identify virulence markers by evaluating the primary and
      secondary structures of the 5'-untranslated region of low and high virulence
      bovine viral diarrhea virus genotype 2 isolates. The nucleotide sequences of the
      entire 5'-untranslated region mRNA of eight bovine viral diarrhea virus genotype
      2 isolates, four of high virulence and four of low virulence, and two genotype 1
      reference isolates were determined using a polymerase chain reaction and a 5'
      Rapid Amplification of cDNA Ends System. Two nucleotide substitutions were
      identified in the internal ribosomal entry site that distinguished the high
      virulence from the low virulence genotype 2 isolates. The low virulence isolates
      had a cytosine at position 219, whereas the high virulence isolates had a uracil.
      At position 278, a uracil or cytosine was found in the low and high virulence
      groups, respectively. The substituted bases are virulence markers that were used
      to identify bovine viral diarrhea virus genotype 2 isolates of high virulence.

PMID- 9770431
TI  - Functional comparisons among members of the poxvirus T1/35kDa family of soluble
      CC-chemokine inhibitor glycoproteins.
AB  - Many poxviruses express a 35-40-kDa secreted protein, termed "T1" (for
      leporipoxviruses) or "35kDa" (for orthopoxviruses), that binds CC-chemokines with
      high affinity but is unrelated to any known cellular proteins. Many previously
      identified poxvirus cytokine-binding proteins display strict species ligand
      binding specificity. Because the T1 and 35kDa proteins share only 40% amino acid
      identity, we compared the abilities of purified myxoma virus-T1 (M-T1) and
      vaccinia virus (strain Lister)- and rabbitpox virus-35kDa proteins to inhibit
      human CC-chemokines in vitro. All three proteins were equally effective in
      preventing several human CC-chemokines from binding to target chemokine receptors
      and blocking subsequent intracellular calcium release. The inhibitory affinities
      were comparable (Ki = 0.07-1.02 nM). These proteins also displayed similar
      abilities to inhibit (IC50 = 6.3-10.5 nM) human macrophage inflammatory protein
      1alpha-mediated chemotaxis of human monocytes. None of the viral proteins blocked
      interleukin-8-mediated calcium flux or chemotaxis of human neutrophils,
      confirming that the biological specificity of the T1/35kDa family is targeted
      inhibition of CC-chemokines. Despite the significant sequence divergence between
      the leporipoxvirus T1 and orthopoxvirus 35kDa proteins, our data suggest that
      their CC-chemokine binding and inhibitory properties appear to be species
      nonspecific and that the critical motifs most likely reside within the limited
      regions of conservation.

PMID- 9770432
TI  - The site-specific recombination system of the Lactobacillus species bacteriophage
      A2 integrates in gram-positive and gram-negative bacteria.
AB  - The region of the bacteriophage A2 genome involved in site-specific recombination
      with the DNA of Lactobacillus spp. has been identified. Two orfs, transcribed
      from the same strand, have been found immediately upstream of the phage
      attachment site (attP). The orf adjacent to attP predicts a 385-amino-acid
      protein that presents significant similarity with site-specific recombinases of
      the integrase family. The other orf encodes a basic polypeptide of 76 amino acid
      residues. The junctions of the prophage with the genomes of its hosts have been
      determined, allowing the identification of the host attachment site (attB), which
      has a common 19-nucleotide core region with attP. The attB site is located at the
      3' end of the transfer RNALeu gene (anticodon CAA). Nonreplicative plasmids
      containing the A2-specific recombination cassette integrate into different
      lactobacilli but also into unrelated Gram-positive bacteria such as Lactococcus
      lactis and even into Escherichia coli. In Lc. lactis, integration occurs in a
      previously unknown intergenic region, whereas in E. coli, it maps within the rrnD
      operon, 5' of rrsD gene. Comparison of the integration sites in the different
      hosts indicates that some flexibility is permitted in the attB sequence, since
      Lc. lactis and E. coli only share 13 and 11 nucleotides, respectively, with the
      19-nucleotide core sequence of the lactobacilli.

PMID- 9770435
TI  - The 41-kDa protein of human herpesvirus 6 specifically binds to viral DNA
      polymerase and greatly increases DNA synthesis.
AB  - We previously isolated a 41-kDa early antigen of human herpesvirus 6 (HHV-6),
      which exhibited nuclear localization and DNA-binding activity (Agulnick et al.,
      1993). In this study, we observed that a 110-kDa protein was coimmunoprecipitated
      with p41 from HHV-6-infected cells by an anti-p41 antibody. This 110-kDa protein
      was identified as the HHV-6 DNA polymerase (Pol-6) by an antibody raised against
      the N terminus of Pol-6. Reciprocal immunoprecipitation and Western blot analyses
      confirmed that p41 complexes with Pol-6 in HHV-6-infected cells. In addition,
      both p41 and Pol-6 were expressed in vitro and shown to form a specific complex.
      An in vitro DNA synthesis assay using primed M13 single-stranded DNA template
      demonstrated that p41 not only increased the DNA synthesis activity of Pol-6 but
      also allowed Pol-6 to synthesize DNA products corresponding to full-length M13
      template (7249 nucleotides). By contrast, Pol-6 alone could only synthesize DNA
      of <100 nucleotides. The functional interaction between Pol-6 and p41 appears to
      be specific because they could not be physically or functionally substituted in
      vitro by their herpes simplex virus 1 homologues. Moreover, as revealed by
      mutational analysis, both the N and C termini of Pol-6 contribute to its binding
      to p41. In the case of p41, the N terminus is required for increasing DNA
      synthesis but not binding to Pol-6, whereas the C terminus is totally
      dispensable.

PMID- 9770433
TI  - Cells expressing the human foamy virus (HFV) accessory Bet protein are resistant
      to productive HFV superinfection.
AB  - Bet is a foamy virus (FV) accessory protein not required for virus replication.
      The function of Bet is not understood. We report on the generation of cell lines
      stably expressing the HFV Bet protein. In Bet+ cells, HFV replication was reduced
      by approximately 3-4 orders of magnitude compared with control cells. The HFV Bet
      expressing cells only partially resisted infection by the distantly related
      feline FV (FFV). Pseudotyping experiments, using murine retroviral vectors with
      an HFV envelope, revealed that the resistance was not due to downregulation of
      the unknown HFV receptor. In transfection experiments, using proviral reporter
      gene constructs and infectious proviruses, no significant differences were
      detected between Bet+ and control cells. In infection experiments, HFV vectors
      expressing an indicator gene under control of the HFV promoters showed no
      activity in Bet+ cells. The results are best compatible with the hypothesis that
      the main block to productive superinfection of Bet+ cells occurs at an early
      stage of replication between virus entry and provirus establishment. We suggest
      that inhibition of provirus integration by Bet protein may serve a distinct
      function in the unique foamy virus replication cycle.

PMID- 9770434
TI  - Varicella-zoster virus ORF57, unlike its pseudorabies virus UL3.5 homolog, is
      dispensable for viral replication in cell culture.
AB  - Varicella zoster virus (VZV) encodes five genes that do not have homologs in
      herpes simplex virus. One of these genes, VZV ORF57, is predicted to encode a
      protein containing 71 amino acids. Antibody to ORF57 protein immunoprecipitated a
      6-kDa protein in the cytosol of VZV-infected cells. Although the homolog of VZV
      ORF57 in pseudorabies virus, UL3.5, is critical for viral egress and growth in
      cell culture, VZV unable to express ORF57 replicated to titers similar to those
      seen with parental virus. Thus VZV ORF57 has a different role in viral
      replication than its pseudorabies virus homolog.

PMID- 9770436
TI  - Construction and characterization of E3-deleted bovine adenovirus type 3
      expressing full-length and truncated form of bovine herpesvirus type 1
      glycoprotein gD.
AB  - Using the homologous recombination machinery of E. coli, a 1.245-kb deletion was
      introduced in the E3 region of bovine adenovirus 3 (BAV3) genomic DNA cloned in a
      plasmid. Transfection of the restriction enzyme-excised, linear E3-deleted BAV3
      genomic DNA into primary fetal bovine retina cells produced infectious virus
      (BAV3. E3d), suggesting that all the E3-specific open reading frames are
      nonessential for virus replication in vitro. Using a similar approach, we
      constructed replication-competent (BAV3.E3gD and BAV3. E3gDt) BAV3 recombinant
      expressing full-length (gD) or truncated (gDt) glycoprotein of bovine herpes
      virus 1. Recombinant gD and gDt proteins expressed by BAV3.E3gD and BAV3.E3gDt,
      respectively, were recognized by gD-specific monoclonal antibodies directed
      against conformational epitopes, suggesting that antigenicity of recombinant gD
      and gDt was similar to that of the native gD expressed in bovine herpes virus 1
      infected cells. Intranasal immunization of cotton rats induced strong gD- and
      BAV3-specific IgA and IgG immune responses. These results suggest that
      replication-competent bovine adenovirus 3-based vectors have potential for the
      delivery of vaccine antigens to the mucosal surfaces of animals.

PMID- 9770437
TI  - Particle-bombardment-mediated DNA vaccination with rotavirus VP4 or VP7 induces
      high levels of serum rotavirus IgG but fails to protect mice against challenge.
AB  - We recently reported that epidermal immunization using the PowderJet particle
      delivery device with plasmid vector pcDNA1/EDIM6 encoding rotavirus VP6 of murine
      strain EDIM induced high levels of serum rotavirus IgG but failed to protect mice
      against EDIM infection (Choi, A. H., Knowlton, D. R., McNeal, M. M., and Ward, R.
      L. (1997) Virology 232, 129-138.). This was extended to determine whether
      pcDNA1/EDIM4 or pcDNA1/EDIM7, which encode either rotavirus VP4 or VP7, the
      rotavirus neutralization proteins, could also induce rotavirus-specific antibody
      responses and if these responses resulted in protection. Titers of rotavirus
      serum IgG increased with the first dose in mice immunized with pcDNA1/EDIM7, but
      little or no serum rotavirus IgG was detected in mice immunized with
      pcDNA1/EDIM4. In vitro assays with these plasmids in rabbit reticulocyte lysates
      showed that VP4 was expressed but the amount was considerably lower than VP6 or
      VP7. To improve expression of VP4 and induction of rotavirus-specific humoral
      responses, the coding region of VP4 was cloned into the high-expression plasmid
      WRG7054 as a fusion protein containing the 22-amino-acid secretory signal peptide
      of tissue plasminogen activator (tPA) at its N terminus. In vitro expression of
      tPA::VP4 was significantly higher than unmodified VP4, and mice inoculated with
      WRG7054/EDIM4 generated high titers of rotavirus IgG. The coding sequence of VP7
      without the first 162 nucleotides was also cloned into WRG7054, but no difference
      was observed between titers of serum rotavirus IgG in mice immunized with this
      plasmid (WRG7054/EDIM7Delta1-162) and pcDNA1/EDIM7. The rotavirus-specific IgG
      titers in all immune sera were predominantly IgG1 indicating induction of Th 2
      type responses. None of the mice immunized with any of the VP4 or VP7 plasmids
      developed serum or fecal rotavirus IgA or neutralizing antibody to EDIM. When
      immunized mice were challenged with EDIM virus, there was no significant
      reduction in viral shedding relative to unimmunized controls. Therefore epidermal
      immunization with VP4 or VP7 alone elicited rotavirus IgG responses but did not
      protect against homologous rotavirus challenge.

PMID- 9770440
TI  - A role for the beta-amyloid precursor protein in memory?

PMID- 9770438
TI  - Internal ribosomal entry site scanning of the poliovirus polyprotein:
      implications for proteolytic processing.
AB  - Based on previous studies of dicistronic polioviruses carrying two internal
      ribosomal entry sites (IRESes), we performed a novel experiment of IRES scanning
      through a polypeptide by inserting sequentially the IRES of encephalomyocarditis
      virus into the open reading frame (ORF) of the poliovirus polyprotein at selected
      3Cpro-specific Q*G cleavage sites. No cytopathic effects were observed after
      transfection of HeLa cells with any of the dicistronic constructs, and no virus
      was recovered. In vitro translation of the dicistronic RNA transcripts in HeLa
      cell-free extracts revealed that multiple defects in the processing of the P2-P3
      domain of the polyprotein is the primary reason for the lethal phenotypes.
      Surprisingly, the interruption of 3Cpro-catalyzed cleavages downstream of 2C
      interfered with the 2Apro-catalyzed, primary cleavage between P1 and P2. In
      contrast, insertion of a foreign coding sequence (V3 loop of human
      immunodeficiency virus type 1 gp120) into the ORF of the polyprotein at the 2C-3A
      junction yielded a viable virus that appeared to be genetically stable over
      several passages. The results of these experiments, which are generally
      applicable to analyses of viral polyproteins or multidomain polypeptides, suggest
      that processing of the P2-P3 domain by 3C-3CDpro is rapid and accurate only in
      the context of the unperturbed P2-P3 precursor; this is consistent with cleavages
      occurring in cis. Moreover, an intact 2C-3A precursor is not required for viral
      proliferation.

PMID- 9770442
TI  - Identifying the genes of hearing, deafness, and dysequilibrium.

PMID- 9770441
TI  - Cell death throes.

PMID- 9770443
TI  - A peptide that inhibits hydroxyapatite growth is in an extended conformation on
      the crystal surface.
AB  - Proteins play an important role in the biological mechanisms controlling hard
      tissue development, but the details of molecular recognition at inorganic crystal
      interfaces remain poorly characterized. We have applied a recently developed
      homonuclear dipolar recoupling solid-state NMR technique, dipolar recoupling with
      a windowless sequence (DRAWS), to directly probe the conformation of an acidic
      peptide adsorbed to hydroxyapatite (HAP) crystals. The phosphorylated
      hexapeptide, DpSpSEEK (N6, where pS denotes phosphorylated serine), was derived
      from the N terminus of the salivary protein statherin. Constant-composition
      kinetic characterization demonstrated that, like the native statherin, this
      peptide inhibits the growth of HAP seed crystals when preadsorbed to the crystal
      surface. The DRAWS technique was used to measure the internuclear distance
      between two 13C labels at the carbonyl positions of the adjacent phosphoserine
      residues. Dipolar dephasing measured at short mixing times yielded a mean
      separation distance of 3.2 +/- 0.1 A. Data obtained by using longer mixing times
      suggest a broad distribution of conformations about this average distance. Using
      a more complex model with discrete alpha-helical and extended conformations did
      not yield a better fit to the data and was not consistent with chemical shift
      analysis. These results suggest that the peptide is predominantly in an extended
      conformation rather than an alpha-helical state on the HAP surface. Solid-state
      NMR approaches can thus be used to determine directly the conformation of
      biologically relevant peptides on HAP surfaces. A better understanding of peptide
      and protein conformation on biomineral surfaces may provide design principles
      useful for the modification of orthopedic and dental implants with coatings and
      biological growth factors that are designed to enhance biocompatibility with
      surrounding tissue.

PMID- 9770444
TI  - From ab initio quantum mechanics to molecular neurobiology: a cation-pi binding
      site in the nicotinic receptor.
AB  - The nicotinic acetylcholine receptor is the prototype ligand-gated ion channel. A
      number of aromatic amino acids have been identified as contributing to the
      agonist binding site, suggesting that cation-pi interactions may be involved in
      binding the quaternary ammonium group of the agonist, acetylcholine. Here we show
      a compelling correlation between: (i) ab initio quantum mechanical predictions of
      cation-pi binding abilities and (ii) EC50 values for acetylcholine at the
      receptor for a series of tryptophan derivatives that were incorporated into the
      receptor by using the in vivo nonsense-suppression method for unnatural amino
      acid incorporation. Such a correlation is seen at one, and only one, of the
      aromatic residues-tryptophan-149 of the alpha subunit. This finding indicates
      that, on binding, the cationic, quaternary ammonium group of acetylcholine makes
      van der Waals contact with the indole side chain of alpha tryptophan-149,
      providing the most precise structural information to date on this receptor.
      Consistent with this model, a tethered quaternary ammonium group emanating from
      position alpha149 produces a constitutively active receptor.

PMID- 9770445
TI  - Ionophores and receptors using cation-pi interactions: collarenes.
AB  - Cation-pi interactions are important forces in molecular recognition by
      biological receptors, enzyme catalysis, and crystal engineering. We have
      harnessed these interactions in designing molecular systems with circular
      arrangement of benzene units that are capable of acting as ionophores and models
      for biological receptors. [n]Collarenes are promising candidates with high
      selectivity for a specific cation, depending on n, because of their structural
      rigidity and well-defined cavity size. The interaction energies of [n]collarenes
      with cations have been evaluated by using ab initio calculations. The selectivity
      of these [n]collarenes in aqueous solution was revealed by using statistical
      perturbation theory in conjunction with Monte Carlo and molecular dynamics
      simulations. It has been observed that in [n]collarenes the ratio of the
      interaction energies of a cation with it and the cation with the basic building
      unit (benzene) can be correlated to its ion selectivity. We find that collarenes
      are excellent and efficient ionophores that bind cations through cation-pi
      interactions. [6]Collarene is found to be a selective host for Li+ and Mg2+,
      [8]collarene for K+ and Sr2+, and [10]collarene for Cs+ and Ba2+. This finding
      indicates that [10]collarene and [8]collarene could be used for effective
      separation of highly radioactive isotopes, 137Cs and 90Sr, which are major
      constituents of nuclear wastes. More interestingly, collarenes of larger cavity
      size can be useful in capturing organic cations. [12]Collarene exhibits a
      pronounced affinity for tetramethylammonium cation and acetylcholine, which
      implies that it could serve as a model for acetylcholinestrase. Thus, collarenes
      can prove to be novel and effective ionophores/model-receptors capable of
      heralding a new direction in molecular recognition and host-guest chemistry.

PMID- 9770446
TI  - Role of calpain in skeletal-muscle protein degradation.
AB  - Although protein degradation is enhanced in muscle-wasting conditions and limits
      the rate of muscle growth in domestic animals, the proteolytic system responsible
      for degrading myofibrillar proteins in skeletal muscle is not well defined. The
      goals of this study were to evaluate the roles of the calpains (calcium-activated
      cysteine proteases) in mediating muscle protein degradation and the extent to
      which these proteases participate in protein turnover in muscle. Two strategies
      to regulate intracellular calpain activities were developed: overexpression of
      dominant-negative m-calpain and overexpression of calpastatin inhibitory domain.
      To express these constructs, L8 myoblast cell lines were transfected with
      LacSwitch plasmids, which allowed for isopropyl beta-D-thiogalactoside-dependent
      expression of the gene of interest. Inhibition of calpain stabilized fodrin, a
      well characterized calpain substrate. Under conditions of accelerated degradation
      (serum withdrawal), inhibition of m-calpain reduced protein degradation by 30%,
      whereas calpastatin inhibitory domain expression reduced degradation by 63%.
      Inhibition of calpain also stabilized nebulin. These observations indicate that
      calpains play key roles in the disassembly of sarcomeric proteins. Inhibition of
      calpain activity may have therapeutic value in treatment of muscle-wasting
      conditions and may enhance muscle growth in domestic animals.

PMID- 9770447
TI  - Transgenic DNA integrated into the oat genome is frequently interspersed by host
      DNA.
AB  - Integration of transgenic DNA into the plant genome was investigated in 13
      transgenic oat (Avena sativa L.) lines produced using microprojectile bombardment
      with one or two cotransformed plasmids. In all transformation events, the
      transgenic DNA integrated into the plant genome consisted of intact transgene
      copies that were accompanied by multiple, rearranged, and/or truncated transgene
      fragments. All fragments of transgenic DNA cosegregated, indicating that they
      were integrated at single gene loci. Analysis of the structure of the transgenic
      loci indicated that the transgenic DNA was interspersed by the host genomic DNA.
      The number of insertions of transgenic DNA within the transgene loci varied from
      2 to 12 among the 13 lines. Restriction endonucleases that do not cleave the
      introduced plasmids produced restriction fragments ranging from 3.6 to about 60
      kb in length hybridizing to a probe comprising the introduced plasmids. Although
      the size of the interspersing host DNA within the transgene locus is unknown, the
      sizes of the transgene-hybridizing restriction fragments indicated that the
      entire transgene locus must be at least from 35-280 kb. The observation that all
      transgenic lines analyzed exhibited genomic interspersion of multiple clustered
      transgenes suggests a predominating integration mechanism. We propose that
      transgene integration at multiple clustered DNA replication forks could account
      for the observed interspersion of transgenic DNA with host genomic DNA within
      transgenic loci.

PMID- 9770448
TI  - A gene cluster for macrolide antibiotic biosynthesis in Streptomyces venezuelae:
      architecture of metabolic diversity.
AB  - In a survey of microbial systems capable of generating unusual metabolite
      structural variability, Streptomyces venezuelae ATCC 15439 is notable in its
      ability to produce two distinct groups of macrolide antibiotics. Methymycin and
      neomethymycin are derived from the 12-membered ring macrolactone 10
      deoxymethynolide, whereas narbomycin and pikromycin are derived from the 14
      membered ring macrolactone, narbonolide. This report describes the cloning and
      characterization of the biosynthetic gene cluster for these antibiotics. Central
      to the cluster is a polyketide synthase locus (pikA) that encodes a six-module
      system comprised of four multifunctional proteins, in addition to a type II
      thioesterase (TEII). Immediately downstream is a set of genes for desosamine
      biosynthesis (des) and macrolide ring hydroxylation. The study suggests that Pik
      TEII plays a role in forming a metabolic branch through which polyketides of
      different chain length are generated, and the glycosyl transferase (encoded by
      desVII) has the ability to catalyze glycosylation of both the 12- and 14-membered
      ring macrolactones. Moreover, the pikC-encoded P450 hydroxylase provides yet
      another layer of structural variability by introducing regiochemical diversity
      into the macrolide ring systems. The data support the notion that the
      architecture of the pik gene cluster as well as the unusual substrate specificity
      of particular enzymes contributes to its ability to generate four macrolide
      antibiotics.

PMID- 9770449
TI  - Inhibition of protease-resistant prion protein formation by porphyrins and
      phthalocyanines.
AB  - A central aspect of pathogenesis in the transmissible spongiform encephalopathies
      or prion diseases is the conversion of normal protease-sensitive prion protein
      (PrP-sen) to the abnormal protease-resistant form, PrP-res. Here we identify
      porphyrins and phthalocyanines as inhibitors of PrP-res accumulation. The most
      potent of these tetrapyrroles had IC50 values of 0.5-1 microM in scrapie-infected
      mouse neuroblastoma (ScNB) cell cultures. Inhibition was observed without effects
      on protein biosynthesis in general or PrP-sen biosynthesis in particular.
      Tetrapyrroles also inhibited PrP-res formation in a cell-free reaction composed
      predominantly of hamster PrP-res and PrP-sen. Inhibitors were found among
      phthalocyanines, deuteroporphyrins IX, and meso-substituted porphines; examples
      included compounds containing anionic, neutral protic, and cationic peripheral
      substituents and various metals. We conclude that certain tetrapyrroles
      specifically inhibit the conversion of PrP-sen to PrP-res without apparent
      cytotoxic effects. The inhibition observed in the cell-free conversion reaction
      suggests that the mechanism involved direct interactions of the tetrapyrrole with
      PrP-res and/or PrP-sen. These findings introduce a new class of inhibitors of PrP
      res formation that represents a potential source of therapeutic agents for
      transmissible spongiform encephalopathies.

PMID- 9770450
TI  - Crystal structure of the BTB domain from PLZF.
AB  - The BTB domain (also known as the POZ domain) is an evolutionarily conserved
      protein-protein interaction motif found at the N terminus of 5-10% of C2H2-type
      zinc-finger transcription factors, as well as in some actin-associated proteins
      bearing the kelch motif. Many BTB proteins are transcriptional regulators that
      mediate gene expression through the control of chromatin conformation. In the
      human promyelocytic leukemia zinc finger (PLZF) protein, the BTB domain has
      transcriptional repression activity, directs the protein to a nuclear punctate
      pattern, and interacts with components of the histone deacetylase complex. The
      association of the PLZF BTB domain with the histone deacetylase complex provides
      a mechanism of linking the transcription factor with enzymatic activities that
      regulate chromatin conformation. The crystal structure of the BTB domain of PLZF
      was determined at 1.9 A resolution and reveals a tightly intertwined dimer with
      an extensive hydrophobic interface. Approximately one-quarter of the monomer
      surface area is involved in the dimer intermolecular contact. These features are
      typical of obligate homodimers, and we expect the full-length PLZF protein to
      exist as a branched transcription factor with two C-terminal DNA-binding regions.
      A surface-exposed groove lined with conserved amino acids is formed at the dimer
      interface, suggestive of a peptide-binding site. This groove may represent the
      site of interaction of the PLZF BTB domain with nuclear corepressors or other
      nuclear proteins.

PMID- 9770451
TI  - Structure of the Ets-1 pointed domain and mitogen-activated protein kinase
      phosphorylation site.
AB  - The Pointed (PNT) domain and an adjacent mitogen-activated protein (MAP) kinase
      phosphorylation site are defined by sequence conservation among a subset of ets
      transcription factors and are implicated in two regulatory strategies, protein
      interactions and posttranslational modifications, respectively. By using NMR, we
      have determined the structure of a 110-residue fragment of murine Ets-1 that
      includes the PNT domain and MAP kinase site. The Ets-1 PNT domain forms a
      monomeric five-helix bundle. The architecture is distinct from that of any known
      DNA- or protein-binding module, including the helix-loop-helix fold proposed for
      the PNT domain of the ets protein TEL. The MAP kinase site is in a highly
      flexible region of both the unphosphorylated and phosphorylated forms of the Ets
      1 fragment. Phosphorylation alters neither the structure nor monomeric state of
      the PNT domain. These results suggest that the Ets-1 PNT domain functions in
      heterotypic protein interactions and support the possibility that target
      recognition is coupled to structuring of the MAP kinase site.

PMID- 9770452
TI  - The role of the ClpA chaperone in proteolysis by ClpAP.
AB  - ClpA, a member of the Clp/Hsp100 family of ATPases, is a molecular chaperone and,
      in combination with a proteolytic component ClpP, participates in ATP-dependent
      proteolysis. We investigated the role of ClpA in protein degradation by ClpAP by
      dissociating the reaction into several discrete steps. In the assembly step, ClpA
      ClpP-substrate complexes assemble either by ClpA-substrate complexes interacting
      with ClpP or by ClpA-ClpP complexes interacting with substrate; ClpP in the
      absence of ClpA is unable to bind substrates. Assembly requires ATP binding but
      not hydrolysis. We discovered that ClpA translocates substrates from their
      binding sites on ClpA to ClpP. The translocation step specifically requires ATP;
      nonhydrolyzable ATP analogs are ineffective. Only proteins that are degraded by
      ClpAP are translocated. Characterization of the degradation step showed that
      substrates can be degraded in a single round of ClpA-ClpP-substrate binding
      followed by ATP hydrolysis. The products generated are indistinguishable from
      steady-state products. Taken together, our results suggest that ClpA, through its
      interaction with both the substrate and ClpP, acts as a gatekeeper, actively
      translocating specific substrates into the proteolytic chamber of ClpP where
      degradation occurs. As multicomponent ATP-dependent proteases are widespread in
      nature and share structural similarities, these findings may provide a general
      mechanism for regulation of substrate import into the proteolytic chamber.

PMID- 9770453
TI  - Oligomerization domain-directed reassembly of active dihydrofolate reductase from
      rationally designed fragments.
AB  - Reassembly of enzymes from peptide fragments has been used as a strategy for
      understanding the evolution, folding, and role of individual subdomains in
      catalysis and regulation of activity. We demonstrate an oligomerization-assisted
      enzyme reassembly strategy whereby fragments are covalently linked to
      independently folding and interacting domains whose interactions serve to promote
      efficient refolding and complementation of fragments, forming active enzyme. We
      show that active murine dihydrofolate reductase (E.C. 1.5.1.3) can be reassembled
      from complementary N- and C-terminal fragments when fused to homodimerizing GCN4
      leucine zipper-forming sequences as well as heterodimerizing protein partners.
      Reassembly is detected by an in vivo selection assay in Escherichia coli and in
      vitro. The effects of mutations that disrupt fragment affinity or enzyme activity
      were assessed. The steady-state kinetic parameters for the reassembled mutant
      (Phe-31 --> Ser) were determined; they are not significantly different from the
      full-length mutant. The strategy described here provides a general approach for
      protein dissection and domain swapping studies, with the capacity both for rapid
      in vivo screening as well as in vitro characterization. Further, the strategy
      suggests a simple in vivo enzyme-based detection system for protein-protein
      interactions, which we illustrate with two examples: ras-GTPase and raf-ras
      binding domain and FK506-binding protein-rapamycin complexed with the target of
      rapamycin TOR2.

PMID- 9770454
TI  - Complex gangliosides are essential in spermatogenesis of mice: possible roles in
      the transport of testosterone.
AB  - Mice, homozygous for disrupted ganglioside GM2/GD2 synthase (EC 2.4. 1.94) gene
      and lacking all complex gangliosides, do not display any major neurologic
      abnormalities. Further examination of these mutant mice, however, revealed that
      the males were sterile and aspermatogenic. In the seminiferous tubules of the
      mutant mice, a number of multinuclear giant cells and vacuolated Sertoli cells
      were observed. The levels of testosterone in the serum of these mice were very
      low, although testosterone production equaled that produced in wild-type mice.
      Testosterone was found to be accumulated in interstitial Leydig cells, and
      intratesticularly injected testosterone was poorly drained in seminiferous fluid
      in the mutant mice. These results suggested that complex gangliosides are
      essential in the transport of testosterone to the seminiferous tubules and
      bloodstream from Leydig cells. Our results provide insights into roles of
      gangliosides in vivo.

PMID- 9770455
TI  - The anti-angiogenic agent fumagillin covalently modifies a conserved active-site
      histidine in the Escherichia coli methionine aminopeptidase.
AB  - Methionine aminopeptidase (MetAP) exists in two forms (type I and type II), both
      of which remove the N-terminal methionine from proteins. It previously has been
      shown that the type II enzyme is the molecular target of fumagillin and ovalicin,
      two epoxide-containing natural products that inhibit angiogenesis and suppress
      tumor growth. By using mass spectrometry, N-terminal sequence analysis, and
      electronic absorption spectroscopy we show that fumagillin and ovalicin
      covalently modify a conserved histidine residue in the active site of the MetAP
      from Escherichia coli, a type I enzyme. Because all of the key active site
      residues are conserved, it is likely that a similar modification occurs in the
      type II enzymes. This modification, by occluding the active site, may prevent the
      action of MetAP on proteins or peptides involved in angiogenesis. In addition,
      the results suggest that these compounds may be effective pharmacological agents
      against pathogenic and resistant forms of E. coli and other microorganisms.

PMID- 9770456
TI  - Polyadenylation of stable RNA precursors in vivo.
AB  - Polyadenylation at the 3' terminus has long been considered a specific feature of
      mRNA and a few other unstable RNA species. Here we show that stable RNAs in
      Escherichia coli can be polyadenylated as well. RNA molecules with poly(A) tails
      are the major products that accumulate for essentially all stable RNA precursors
      when RNA maturation is slowed because of the absence of processing
      exoribonucleases; poly(A) tails vary from one to seven residues in length. The
      polyadenylation process depends on the presence of poly(A) polymerase I. A
      stochastic competition between the exoribonucleases and poly(A) polymerase is
      proposed to explain the accumulation of polyadenylated RNAs. These data indicate
      that polyadenylation is not unique to mRNA, and its widespread occurrence
      suggests that it serves a more general function in RNA metabolism.

PMID- 9770458
TI  - Enhanced transcription factor access to arrays of histone H3/H4 tetramer.DNA
      complexes in vitro: implications for replication and transcription.
AB  - Defined model systems consisting of physiologically spaced arrays of H3/H4
      tetramer.5S rDNA complexes have been assembled in vitro from pure components.
      Analytical hydrodynamic and electrophoretic studies have revealed that the
      structural features of H3/H4 tetramer arrays closely resemble those of naked DNA.
      The reptation in agarose gels of H3/H4 tetramer arrays is essentially
      indistinguishable from naked DNA, the gel-free mobility of H3/H4 tetramer arrays
      relative to naked DNA is reduced by only 6% compared with 20% for nucleosomal
      arrays, and H3/H4 tetramer arrays are incapable of folding under ionic conditions
      where nucleosomal arrays are extensively folded. We further show that the cognate
      binding sites for transcription factor TFIIIA are significantly more accessible
      when the rDNA is complexed with H3/H4 tetramers than with histone octamers. These
      results suggest that the processes of DNA replication and transcription have
      evolved to exploit the unique structural properties of H3/H4 tetramer arrays.

PMID- 9770457
TI  - GroEL-GroES-mediated protein folding requires an intact central cavity.
AB  - The chaperonin GroEL is an oligomeric double ring structure that, together with
      the cochaperonin GroES, assists protein folding. Biochemical analyses indicate
      that folding occurs in a cis ternary complex in which substrate is sequestered
      within the GroEL central cavity underneath GroES. Recently, however, studies of
      GroEL "minichaperones" containing only the apical substrate binding subdomain
      have questioned the functional importance of substrate encapsulation within GroEL
      GroES complexes. Minichaperones were reported to assist folding despite the fact
      that they are monomeric and therefore cannot form a central cavity. Here we
      compare directly the folding activity of minichaperones with that of the full
      GroEL-GroES system. In agreement with earlier studies, minichaperones assist
      folding of some proteins. However, this effect is observed only under conditions
      where substantial spontaneous folding is also observed and is indistinguishable
      from that resulting from addition of the nonchaperone protein alpha-casein. By
      contrast, the full GroE system efficiently promotes folding of several substrates
      under conditions where essentially no spontaneous folding is observed. These data
      argue that the full GroEL folding activity requires the intact GroEL-GroES
      complex, and in light of previous studies, underscore the importance of substrate
      encapsulation for providing a folding environment distinct from the bulk
      solution.

PMID- 9770459
TI  - The helical domain of intestinal fatty acid binding protein is critical for
      collisional transfer of fatty acids to phospholipid membranes.
AB  - Fatty acid binding proteins (FABPs) exhibit a beta-barrel topology, comprising 10
      antiparallel beta-sheets capped by two short alpha-helical segments. Previous
      studies suggested that fatty acid transfer from several FABPs occurs during
      interaction between the protein and the acceptor membrane, and that the helical
      domain of the FABPs plays an important role in this process. In this study, we
      employed a helix-less variant of intestinal FABP (IFABP-HL) and examined the rate
      and mechanism of transfer of fluorescent anthroyloxy fatty acids (AOFA) from this
      protein to model membranes in comparison to the wild type (wIFABP). In marked
      contrast to wIFABP, IFABP-HL does not show significant modification of the AOFA
      transfer rate as a function of either the concentration or the composition of the
      acceptor membranes. These results suggest that the transfer of fatty acids from
      IFABP-HL occurs by an aqueous diffusion-mediated process, i.e., in the absence of
      the helical domain, effective collisional transfer of fatty acids to membranes
      does not occur. Binding of wIFABP and IFABP-HL to membranes was directly analyzed
      by using a cytochrome c competition assay, and it was shown that IFABP-HL was 80%
      less efficient in preventing cytochrome c from binding to membranes than the
      native IFABP. Collectively, these results indicate that the alpha-helical region
      of IFABP is involved in membrane interactions and thus plays a critical role in
      the collisional mechanism of fatty acid transfer from IFABP to phospholipid
      membranes.

PMID- 9770460
TI  - Peptide design by artificial neural networks and computer-based evolutionary
      search.
AB  - A technique for systematic peptide variation by a combination of rational and
      evolutionary approaches is presented. The design scheme consists of five
      consecutive steps: (i) identification of a "seed peptide" with a desired
      activity, (ii) generation of variants selected from a physicochemical space
      around the seed peptide, (iii) synthesis and testing of this biased library, (iv)
      modeling of a quantitative sequence-activity relationship by an artificial neural
      network, and (v) de novo design by a computer-based evolutionary search in
      sequence space using the trained neural network as the fitness function. This
      strategy was successfully applied to the identification of novel peptides that
      fully prevent the positive chronotropic effect of anti-beta1-adrenoreceptor
      autoantibodies from the serum of patients with dilated cardiomyopathy. The seed
      peptide, comprising 10 residues, was derived by epitope mapping from an
      extracellular loop of human beta1-adrenoreceptor. A set of 90 peptides was
      synthesized and tested to provide training data for neural network development.
      De novo design revealed peptides with desired activities that do not match the
      seed peptide sequence. These results demonstrate that computer-based evolutionary
      searches can generate novel peptides with substantial biological activity.

PMID- 9770461
TI  - Natural trans-splicing in carnitine octanoyltransferase pre-mRNAs in rat liver.
AB  - Carnitine octanoyltransferase (COT) transports medium-chain fatty acids through
      the peroxisome. During isolation of a COT clone from a rat liver library, a cDNA
      in which exon 2 was repeated, was characterized. Reverse transcription-PCR
      amplifications of total RNAs from rat liver showed a three-band pattern.
      Sequencing of the fragments revealed that, in addition to the canonical exon
      organization, previously reported [Choi, S. J. et al. (1995) Biochim. Biophys.
      Acta 1264, 215-222], there were two other forms in which exon 2 or exons 2 and 3
      were repeated. The possibility of this exonic repetition in the COT gene was
      ruled out by genomic Southern blot. To study the gene expression, we analyzed RNA
      transcripts by Northern blot after RNase H digestion of total RNA. Three
      different transcripts were observed. Splicing experiments also were carried out
      in vitro with different constructs that contain exon 2 plus the 5' or the 3'
      adjacent intron sequences. Our results indicate that accurate joining of two
      exons 2 occurs by a trans-splicing mechanism, confirming the potential of these
      structures for this process in nature. The trans-splicing can be explained by the
      presence of three exon-enhancer sequences in exon 2. Analysis by Western blot of
      the COT proteins by using specific antibodies showed that two proteins
      corresponding to the expected Mr are present in rat peroxisomes. This is the
      first time that a natural trans-splicing reaction has been demonstrated in
      mammalian cells.

PMID- 9770462
TI  - Efficient recruitment of TFIIB and CBP-RNA polymerase II holoenzyme by an
      interferon-beta enhanceosome in vitro.
AB  - The transcriptional activity of an in vitro assembled human interferon-beta gene
      enhanceosome is highly synergistic. This synergy requires five distinct
      transcriptional activator proteins (ATF2/c-JUN, interferon regulatory factor 1,
      and p50/p65 of NF-kappaB), the high mobility group protein HMG I(Y), and the
      correct alignment of protein-binding sites on the face of the DNA double helix.
      Here, we investigate the mechanisms of enhanceosome-dependent transcriptional
      synergy during preinitiation complex assembly in vitro. We show that the
      stereospecific assembly of the enhanceosome is critical for the efficient
      recruitment of TFIIB into a template-committed TFIID-TFIIA-USA (upstream
      stimulatory activity complex) and for the subsequent recruitment of the RNA
      polymerase II holoenzyme complex. In addition, we provide evidence that
      recruitment of the holoenzyme by the enhanceosome is due, at least in part, to
      interactions between the enhanceosome and the transcriptional coactivator CREB,
      cAMP responsive element binding protein (CBP). These studies reveal a unique role
      of enhanceosomes in the cooperative assembly of the transcription machinery on
      the human interferon-beta promoter.

PMID- 9770463
TI  - Identification of the binding site for Gqalpha on its effector Bruton's tyrosine
      kinase.
AB  - Heterotrimeric G proteins and tyrosine kinases are two major cellular signal
      transducers. Although G proteins are known to activate tyrosine kinases, the
      activation mechanism is not clear. Here, we demonstrate that G protein Gqalpha
      binds directly to the nonreceptor Bruton's tyrosine kinase (Btk) to a region
      composed of a Tec-homology (TH) domain and a sarcoma virus tyrosine kinase (Src)
      homology 3 (SH3) domain both in vitro and in vivo. Only active GTP-bound Gqalpha,
      not inactive GDP-bound Gqalpha, can bind to Btk. Mutations of Btk that disrupt
      its ability to bind Gqalpha also eliminate Btk stimulation by Gqalpha, suggesting
      that this interaction is important for Btk activation. Remarkably, the structure
      of this TH (including a proline-rich sequence) -SH3 fragment of the Btk family of
      tyrosine kinases shows an intramolecular interaction. Furthermore, the crystal
      structure of the Src family of tyrosine kinases reveals that the intramolecular
      interaction of SH3 and its ligand is the major determining factor keeping the
      kinase inactive. Thus, we propose an activation model that entails binding of
      Gqalpha to the TH-SH3 region, thereby disrupting the TH-SH3 intramolecular
      interaction and activating Btk.

PMID- 9770464
TI  - Rsk-2 activity is necessary for epidermal growth factor-induced phosphorylation
      of CREB protein and transcription of c-fos gene.
AB  - Activation by growth factors of the Ras-dependent signaling cascade results in
      the induction of p90 ribosomal S6 kinases (p90(rsk)). These are translocated into
      the nucleus upon phosphorylation by mitogen-activated protein kinases, with which
      p90(rsk) are physically associated in the cytoplasm. In humans there are three
      isoforms of the p90(rsk) family, Rsk-1, Rsk-2, and Rsk-3, which are products of
      distinct genes. Although these isoforms are structurally very similar, little is
      known about their functional specificity. Recently, mutations in the Rsk-2 gene
      have been associated with the Coffin-Lowry syndrome (CLS). We have studied a
      fibroblast cell line established from a CLS patient that bears a nonfunctional
      Rsk-2. Here we document that in CLS fibroblasts there is a drastic attenuation in
      the induced Ser-133 phosphorylation of transcription factor CREB (cAMP response
      element-binding protein) in response to epidermal growth factor stimulation. The
      effect is specific, since response to serum, cAMP, and UV light is unaltered.
      Furthermore, epidermal growth factor-induced expression of c-fos is severely
      impaired in CLS fibroblasts despite normal phosphorylation of serum response
      factor and Elk-1. Finally, coexpression of Rsk-2 in transfected cells results in
      the activation of the c-fos promoter via the cAMP-responsive element. Thus, we
      establish a link in the transduction of a specific growth factor signal to
      changes in gene expression via the phosphorylation of CREB by Rsk-2.

PMID- 9770465
TI  - Identification of a human nuclear receptor defines a new signaling pathway for
      CYP3A induction.
AB  - Nuclear receptors regulate metabolic pathways in response to changes in the
      environment by appropriate alterations in gene expression of key metabolic
      enzymes. Here, a computational search approach based on iteratively built hidden
      Markov models of nuclear receptors was used to identify a human nuclear receptor,
      termed hPAR, that is expressed in liver and intestines. hPAR was found to be
      efficiently activated by pregnanes and by clinically used drugs including
      rifampicin, an antibiotic known to selectively induce human but not murine CYP3A
      expression. The CYP3A drug-metabolizing enzymes are expressed in gut and liver in
      response to environmental chemicals and clinically used drugs. Interestingly,
      hPAR is not activated by pregnenolone 16alpha-carbonitrile, which is a potent
      inducer of murine CYP3A genes and an activator of the mouse receptor PXR.1.
      Furthermore, hPAR was found to bind to and trans-activate through a conserved
      regulatory sequence present in human but not murine CYP3A genes. These results
      provide evidence that hPAR and PXR.1 may represent orthologous genes from
      different species that have evolved to regulate overlapping target genes in
      response to pharmacologically distinct CYP3A activators, and have potential
      implications for the in vitro identification of drug interactions important to
      humans.

PMID- 9770466
TI  - Activation of microhelix charging by localized helix destabilization.
AB  - We report that aminoacylation of minimal RNA helical substrates is enhanced by
      mismatched or unpaired nucleotides at the first position in the helix.
      Previously, we demonstrated that the class I methionyl-tRNA synthetase
      aminoacylates RNA microhelices based on the acceptor stem of initiator and
      elongator tRNAs with greatly reduced efficiency relative to full-length tRNA
      substrates. The cocrystal structure of the class I glutaminyl-tRNA synthetase
      with tRNAGln revealed an uncoupling of the first (1.72) base pair of tRNAGln, and
      tRNAMet was proposed by others to have a similar base-pair uncoupling when bound
      to methionyl-tRNA synthetase. Because the anticodon is important for efficient
      charging of methionine tRNA, we thought that 1.72 distortion is probably effected
      by the synthetase-anticodon interaction. Small RNA substrates (minihelices,
      microhelices, and duplexes) are devoid of the anticodon triplet and may,
      therefore, be inefficiently aminoacylated because of a lack of anticodon
      triggered acceptor stem distortion. To test this hypothesis, we constructed
      microhelices that vary in their ability to form a 1.72 base pair. The results of
      kinetic assays show that microhelix aminoacylation is activated by
      destabilization of this terminal base pair. The largest effect is seen when one
      of the two nucleotides of the pair is completely deleted. Activation of
      aminoacylation is also seen with the analogous deletion in a minihelix substrate
      for the closely related isoleucine enzyme. Thus, for at least the methionine and
      isoleucine systems, a built-in helix destabilization compensates in part for the
      lack of presumptive anticodon-induced acceptor stem distortion.

PMID- 9770467
TI  - Pro-phenol oxidase activating proteinase from an insect, Manduca sexta: a
      bacteria-inducible protein similar to Drosophila easter.
AB  - Activation of pro-phenol oxidase (proPO) in insects and crustaceans is important
      in defense against wounding and infection. The proPO zymogen is activated by a
      specific proteolytic cleavage. PO oxidizes phenolic compounds to produce
      quinones, which may help to kill pathogens and can also be used for synthesis of
      melanin to seal wounds and encapsulate parasites. We have isolated from the
      tobacco hornworm, Manduca sexta, a serine proteinase that activates proPO, and
      have cloned its cDNA. The isolated proPO activating proteinase (PAP) hydrolyzed
      artificial substrates but required other protein factors for proPO activation,
      suggesting that proPO-activating enzyme may exist as a protein complex, one
      component of which is PAP. PAP (44 kDa) is composed of two disulfide-linked
      polypeptide chains (31 kDa and 13 kDa). A cDNA for PAP was isolated from a
      hemocyte library, by using a PCR-generated probe based on the amino-terminal
      amino acid sequence of the 31-kDa catalytic domain. PAP belongs to a family of
      arthropod serine proteinases containing a carboxyl-terminal proteinase domain and
      an amino-terminal "clip" domain. The member of this family most similar in
      sequence to PAP is the product of the easter gene from Drosophila melanogaster.
      PAP mRNA was present at a low level in larval hemocytes and fat body, but became
      much more abundant in fat body after insects were injected with Escherichia coli.
      Sequence data and 3H-diisopropyl fluorphosphate labeling results suggest that the
      same PAP exists in hemolymph and cuticle.

PMID- 9770468
TI  - Mammalian capping enzyme binds RNA and uses protein tyrosine phosphatase
      mechanism.
AB  - Mammalian capping enzymes are bifunctional proteins with both RNA 5'
      triphosphatase and guanylyltransferase activities. The N-terminal 237-aa
      triphosphatase domain contains (I/V)HCXXGXXR(S/T)G, a sequence corresponding to
      the conserved active-site motif in protein tyrosine phosphatases (PTPs). Analysis
      of point mutants of mouse RNA 5'-triphosphatase identified the motif Cys and Arg
      residues and an upstream Asp as required for activity. Like PTPs, this enzyme was
      inhibited by iodoacetate and VO43- and independent of Mg2+, providing additional
      evidence for phosphate removal from RNA 5' ends by a PTP-like mechanism. The full
      length, 597-aa mouse capping enzyme and the C-terminal guanylyltransferase
      fragment (residues 211-597), unlike the triphosphatase domain, bound poly (U) and
      were nuclear in transfected cells. RNA binding was increased by GTP, and a
      guanylylation-defective, active-site mutant was not affected. Ala substitution at
      positions required for the formation of the enzyme-GMP capping intermediate
      (R315, R530, K533, or N537) also eliminated poly (U) binding, while proteins with
      conservative substitutions at these sites retained binding but not
      guanylyltransferase activity. These results demonstrate that the
      guanylyltransferase domain of mammalian capping enzyme specifies nuclear
      localization and RNA binding. Association of capping enzyme with nascent
      transcripts may act in synergy with RNA polymerase II binding to ensure 5' cap
      formation.

PMID- 9770469
TI  - Mass spectrometric evidence for the enzymatic mechanism of the depolymerization
      of heparin-like glycosaminoglycans by heparinase II.
AB  - Heparin-like glycosaminoglycans, acidic complex polysaccharides present on cell
      surfaces and in the extracellular matrix, regulate important physiological
      processes such as anticoagulation and angiogenesis. Heparin-like
      glycosaminoglycan degrading enzymes or heparinases are powerful tools that have
      enabled the elucidation of important biological properties of heparin-like
      glycosaminoglycans in vitro and in vivo. With an overall goal of developing an
      approach to sequence heparin-like glycosaminoglycans using the heparinases, we
      recently have elaborated a mass spectrometry methodology to elucidate the
      mechanism of depolymerization of heparin-like glycosaminoglycans by heparinase I.
      In this study, we investigate the mechanism of depolymerization of heparin-like
      glycosaminoglycans by heparinase II, which possesses the broadest known substrate
      specificity of the heparinases. We show here that heparinase II cleaves heparin
      like glycosaminoglycans endolytically in a nonrandom manner. In addition, we show
      that heparinase II has two distinct active sites and provide evidence that one of
      the active sites is heparinase I-like, cleaving at hexosamine-sulfated iduronate
      linkages, whereas the other is presumably heparinase III-like, cleaving at
      hexosamine-glucuronate linkages. Elucidation of the mechanism of depolymerization
      of heparin-like glycosaminoglycans by the heparinases and mutant heparinases
      could pave the way to the development of much needed methods to sequence heparin
      like glycosaminoglycans.

PMID- 9770470
TI  - rRNA complementarity within mRNAs: a possible basis for mRNA-ribosome
      interactions and translational control.
AB  - Our recent demonstration that many eukaryotic mRNAs contain sequences
      complementary to rRNA led to the hypothesis that these sequences might mediate
      specific interactions between mRNAs and ribosomes and thereby affect translation.
      In the present experiments, the ability of complementary sequences to bind to
      rRNA was investigated by using photochemical cross-linking. RNA probes with
      perfect complementarity to 18S or 28S rRNA were shown to cross-link specifically
      to the corresponding rRNA within intact ribosomal subunits. Similar results were
      obtained by using probes based on natural mRNA sequences with varying degrees of
      complementarity to the 18S rRNA. RNase H cleavage localized four such probes to
      complementary regions of the 18S rRNA. The effects of complementarity on
      translation were assessed by using the mRNA encoding ribosomal protein S15. This
      mRNA contains a sequence within its coding region that is complementary to the
      18S rRNA at 20 of 22 nucleotides. RNA from an S15-luciferase fusion construct was
      translated in a cell-free lysate and compared with the translation of four
      related constructs that were mutated to decrease complementarity to the 18S rRNA.
      These mutations did not alter the amino acid sequence or the codon bias. A
      correlation between complementarity and translation was observed; constructs with
      less complementarity increased the amount of translation up to 54%. These
      findings raised the possibility that direct base-pairing of particular mRNAs to
      rRNAs within ribosomes may function as a mechanism of translational control.

PMID- 9770471
TI  - Identification of 5'-deoxyribose phosphate lyase activity in human DNA polymerase
      gamma and its role in mitochondrial base excision repair in vitro.
AB  - Mitochondria have been proposed to possess base excision repair processes to
      correct oxidative damage to the mitochondrial genome. As the only DNA polymerase
      (pol) present in mitochondria, pol gamma is necessarily implicated in such
      processes. Therefore, we tested the ability of the catalytic subunit of human pol
      gamma to participate in uracil-provoked base excision repair reconstituted in
      vitro with purified components. Subsequent to actions of uracil-DNA glycosylase
      and apurinic/apyrimidinic endonuclease, human pol gamma was able to fill a single
      nucleotide gap in the presence of a 5' terminal deoxyribose phosphate (dRP) flap.
      We report here that the catalytic subunit of human pol gamma catalyzes release of
      the dRP residue from incised apurinic/apyrimidinic sites to produce a substrate
      for DNA ligase. The heat sensitivity of this activity suggests the dRP lyase
      function requires a three-dimensional protein structure. The dRP lyase activity
      does not require divalent metal ions, and the ability to trap covalent enzyme-DNA
      complexes with NaBH4 strongly implicates a Schiff base intermediate in a beta
      elimination reaction mechanism.

PMID- 9770472
TI  - Requirement of GM2 ganglioside activator for phospholipase D activation.
AB  - Sequence analysis of a heat-stable protein necessary for the activation of ADP
      ribosylation factor-dependent phospholipase D (PLD) reveals that this protein has
      a structure highly homologous to the previously known GM2 ganglioside activator
      whose deficiency results in the AB-variant of GM2 gangliosidosis. The heat-stable
      activator protein indeed has the capacity to enhance enzymatic conversion of GM2
      to GM3 ganglioside that is catalyzed by beta-hexosaminidase A. Inversely, GM2
      ganglioside activator purified separately from tissues as described earlier
      [Conzelmann, E. & Sandhoff, K. (1987) Methods Enzymol. 138, 792-815] stimulates
      ADP ribosylation factor-dependent PLD in a dose-dependent manner. At higher
      concentrations of ammonium sulfate, the PLD activator protein apparently
      substitutes for protein kinase C and phosphatidylinositol 4,5-bisphosphate, both
      of which are known as effective stimulators of the PLD reaction. The mechanism of
      action of the heat-stable PLD activator protein remains unknown.

PMID- 9770473
TI  - Activity and nature of p21(WAF1) complexes during the cell cycle.
AB  - Elevated levels of the p21(WAF1) (p21) cyclin-dependent kinase inhibitor induce
      growth arrest. We have characterized a panel of monoclonal antibodies against
      human p21 in an effort to understand the dynamic regulatory interactions between
      this and other cellular proteins during the cell cycle. The use of these reagents
      has allowed us to address several important, yet unresolved, issues concerning
      the biological activity of p21, including the potential kinase activity of
      complexes that associate with this cyclin-dependent kinase inhibitor. We have
      found that the kinase activity of cyclin A/Cdk2 associated with p21 is
      significantly lower than that of cyclin A/Cdk2 free of p21, suggesting that p21
      abolishes its activity in vivo, and the use of multiple antibodies has enabled us
      to begin the study of the molecular architecture of p21 complexes in vivo. In
      addition, we found that human fibroblasts released from a quiescent state display
      abundant amounts of p21 devoid of associated proteins ("free" p21), the levels of
      which decrease as cells approach S phase. Cyclin A levels increase as the amount
      of monomeric p21 decreases, resulting in an excess of cyclin A/Cdk2 complexes
      that are not bound to, or inactivated by, p21. Our data strengthen the notion
      that the G1-to-S phase transition in human fibroblasts occurs when the
      concentration of cyclin A/Cdk2 surpasses that of p21.

PMID- 9770475
TI  - Single prenyl-binding site on protein prenyl transferases.
AB  - Three distinct protein prenyl transferases, one protein farnesyl transferase
      (FTase) and two protein geranylgeranyl transferases (GGTase), catalyze
      prenylation of many cellular proteins. One group of protein substrates contains a
      C-terminal CAAX motif (C is Cys, A is aliphatic, and X is a variety of amino
      acids) in which the single cysteine residue is modified with either farnesyl or
      geranylgeranyl (GG) by FTase or GGTase type-I (GGTase-I), respectively. Rab
      proteins constitute a second group of substrates that contain a C-terminal double
      cysteine motif (such as XXCC in Rab1a) in which both cysteines are
      geranylgeranylated by Rab GG transferase (RabGGTase). Previous characterization
      of CAAX prenyl transferases showed that the enzymes form stable complexes with
      their prenyl pyrophosphate substrates, acting as prenyl carriers. We developed a
      prenyl-binding assay and show that RabGGTase has a prenyl carrier function
      similar to the CAAX prenyl transferases. Stable RabGGTase:GG pyrophosphate
      (GGPP), FTase:GGPP, and GGTase-I:GGPP complexes show 1:1 (enzyme:GGPP)
      stoichiometry. Chromatographic analysis of prenylated products after single
      turnover reactions by using isolated RabGGTase:GGPP complex revealed that Rab is
      mono-geranylgeranylated. This study establishes that all three protein prenyl
      transferases contain a single prenyl-binding site and suggests that RabGGTase
      transfers two GG groups to Rabs in independent and consecutive reactions.

PMID- 9770474
TI  - Identification of thyroid hormone response elements in the human fatty acid
      synthase promoter.
AB  - To investigate the regulation of the human fatty acid synthase gene by the
      thyroid hormone triiodothyronine, various constructs of the human fatty acid
      synthase promoter and the luciferase reporter gene were transfected in
      combination with plasmids expressing the thyroid hormone and the retinoid X
      receptors in HepG2 cells. The reporter gene was activated 25-fold by the thyroid
      hormone in the presence of the thyroid hormone receptor. When both the thyroid
      hormone and the retinoid X receptors were expressed in HepG2 cells, there was
      about a 100-fold increase in reporter gene expression. 5'-Deletion analysis
      disclosed two thyroid hormone response elements, TRE1 (nucleotides -870 to -650)
      and TRE2 (nucleotides -272 to -40), in the human fatty acid synthase promoter.
      The presence of thyroid hormone response elements in these two regions of the
      promoter was confirmed by cloning various fragments of these two regions in the
      minimal thymidine kinase promoter-luciferase reporter gene plasmid construct and
      determining reporter gene expression. The results of this cloning procedure and
      those of electrophoretic mobility shift assays indicated that the sequence
      GGGTTAcgtcCGGTCA (nucleotides -716 to -731) represents TRE1 and that the sequence
      GGGTCC (nucleotides -117 to -112) represents TRE2. The sequence of TRE1 is very
      similar to the consensus sequence of the thyroid hormone response element,
      whereas the sequence of TRE2 contains only a half-site of the thyroid hormone
      response element consensus motif because it lacks the direct repeat. The
      sequences on either side of TRE2 seem to influence its response to the thyroid
      hormone and retinoid X receptors.

PMID- 9770476
TI  - Structural changes in hemoglobin during adsorption to solid surfaces: effects of
      pH, ionic strength, and ligand binding.
AB  - We have studied the adsorption of two structurally similar forms of hemoglobin
      (met-Hb and HbCO) to a hydrophobic self-assembled methyl-terminated thiol
      monolayer on a gold surface, by using a Quartz Crystal Microbalance (QCM)
      technique. This technique allows time-resolved simultaneous measurements of
      changes in frequency (f) (c.f. mass) and energy dissipation (D) (c.f.
      rigidity/viscoelastic properties) of the QCM during the adsorption process, which
      makes it possible to investigate the viscoelastic properties of the different
      protein layers during the adsorption process. Below the isoelectric points of
      both met-Hb and HbCO, the DeltaD vs. Deltaf graphs displayed two phases with
      significantly different slopes, which indicates two states of the adsorbed
      proteins with different visco-elastic properties. The slope of the first phase
      was smaller than that of the second phase, which indicates that the first phase
      was associated with binding of a more rigidly attached, presumably denatured
      protein layer, whereas the second phase was associated with formation of a second
      layer of more loosely bound proteins. This second layer desorbed, e.g., upon
      reduction of Fe3+ of adsorbed met-Hb and subsequent binding of carbon monoxide
      (CO) forming HbCO. Thus, the results suggest that the adsorbed proteins in the
      second layer were in a native-like state. This information could only be obtained
      from simultaneous, time-resolved measurements of changes in both D and f,
      demonstrating that the QCM technique provides unique information about the
      mechanisms of protein adsorption to solid surfaces.

PMID- 9770477
TI  - Temperature dependence of amyloid beta-protein fibrillization.
AB  - Fibrillogenesis of the amyloid beta-protein (Abeta) is believed to play a central
      role in the pathogenesis of Alzheimer's disease. Previous studies of the kinetics
      of Abeta fibrillogenesis showed that the rate of fibril elongation is
      proportional to the concentration of monomers. We report here the study of the
      temperature dependence of the Abeta fibril elongation rate constant, ke, in 0.1 M
      HCl. The rate of fibril elongation was measured at Abeta monomer concentrations
      ranging from 50 to 400 microM and at temperatures from 4 degreesC to 40 degreesC.
      Over this temperature range, ke increases by two orders of magnitude. The
      temperature dependence of ke follows the Arrhenius law, ke = A exp (-EA/kT). The
      preexponential factor A and the activation energy EA are approximately 6 x 10(18)
      liter/(mol.sec) and 23 kcal/mol, respectively. Such a high value of EA suggests
      that significant conformational changes are associated with the binding of Abeta
      monomers to fibril ends.

PMID- 9770478
TI  - Force-mediated kinetics of single P-selectin/ligand complexes observed by atomic
      force microscopy.
AB  - Leukocytes roll along the endothelium of postcapillary venules in response to
      inflammatory signals. Rolling under the hydrodynamic drag forces of blood flow is
      mediated by the interaction between selectins and their ligands across the
      leukocyte and endothelial cell surfaces. Here we present force-spectroscopy
      experiments on single complexes of P-selectin and P-selectin glycoprotein ligand
      1 by atomic force microscopy to determine the intrinsic molecular properties of
      this dynamic adhesion process. By modeling intermolecular and intramolecular
      forces as well as the adhesion probability in atomic force microscopy experiments
      we gain information on rupture forces, elasticity, and kinetics of the P
      selectin/P-selectin glycoprotein ligand-1 interaction. The complexes are able to
      withstand forces up to 165 pN and show a chain-like elasticity with a molecular
      spring constant of 5.3 pN nm-1 and a persistence length of 0.35 nm. The
      dissociation constant (off-rate) varies over three orders of magnitude from 0.02
      s-1 under zero force up to 15 s-1 under external applied forces. Rupture force
      and lifetime of the complexes are not constant, but directly depend on the
      applied force per unit time, which is a product of the intrinsic molecular
      elasticity and the external pulling velocity. The high strength of binding
      combined with force-dependent rate constants and high molecular elasticity are
      tailored to support physiological leukocyte rolling.

PMID- 9770480
TI  - RecA binding to a single double-stranded DNA molecule: a possible role of DNA
      conformational fluctuations.
AB  - Most genetic regulatory mechanisms involve protein-DNA interactions. In these
      processes, the classical Watson-Crick DNA structure sometimes is distorted
      severely, which in turn enables the precise recognition of the specific sites by
      the protein. Despite its key importance, very little is known about such
      deformation processes. To address this general question, we have studied a model
      system, namely, RecA binding to double-stranded DNA. Results from
      micromanipulation experiments indicate that RecA binds strongly to stretched DNA;
      based on this observation, we propose that spontaneous thermal stretching
      fluctuations may play a role in the binding of RecA to DNA. This has fundamental
      implications for the protein-DNA binding mechanism, which must therefore rely in
      part on a combination of flexibility and thermal fluctuations of the DNA
      structure. We also show that this mechanism is sequence sensitive. Theoretical
      simulations support this interpretation of our experimental results, and it is
      argued that this is of broad relevance to DNA-protein interactions.

PMID- 9770479
TI  - The structure and organization within the membrane of the helices composing the
      pore-forming domain of Bacillus thuringiensis delta-endotoxin are consistent with
      an "umbrella-like" structure of the pore.
AB  - The aim of this study was to elucidate the mechanism of membrane insertion and
      the structural organization of pores formed by Bacillus thuringiensis delta
      endotoxin. We determined the relative affinities for membranes of peptides
      corresponding to the seven helices that compose the toxin pore-forming domain,
      their modes of membrane interaction, their structures within membranes, and their
      orientations relative to the membrane normal. In addition, we used resonance
      energy transfer measurements of all possible combinatorial pairs of membrane
      bound helices to map the network of interactions between helices in their
      membrane-bound state. The interaction of the helices with the bilayer membrane
      was also probed by a Monte Carlo simulation protocol to determine lowest-energy
      orientations. Our results are consistent with a situation in which helices alpha4
      and alpha5 insert into the membrane as a helical hairpin in an antiparallel
      manner, while the other helices lie on the membrane surface like the ribs of an
      umbrella (the "umbrella model"). Our results also support the suggestion that
      alpha7 may serve as a binding sensor to initiate the structural rearrangement of
      the pore-forming domain.

PMID- 9770481
TI  - Protein thermostability above 100 degreesC: a key role for ionic interactions.
AB  - The discovery of hyperthermophilic microorganisms and the analysis of
      hyperthermostable enzymes has established the fact that multisubunit enzymes can
      survive for prolonged periods at temperatures above 100 degreesC. We have carried
      out homology-based modeling and direct structure comparison on the hexameric
      glutamate dehydrogenases from the hyperthermophiles Pyrococcus furiosus and
      Thermococcus litoralis whose optimal growth temperatures are 100 degreesC and 88
      degreesC, respectively, to determine key stabilizing features. These enzymes,
      which are 87% homologous, differ 16-fold in thermal stability at 104 degreesC. We
      observed that an intersubunit ion-pair network was substantially reduced in the
      less stable enzyme from T. litoralis, and two residues were then altered to
      restore these interactions. The single mutations both had adverse effects on the
      thermostability of the protein. However, with both mutations in place, we
      observed a fourfold improvement of stability at 104 degreesC over the wild-type
      enzyme. The catalytic properties of the enzymes were unaffected by the mutations.
      These results suggest that extensive ion-pair networks may provide a general
      strategy for manipulating enzyme thermostability of multisubunit enzymes.
      However, this study emphasizes the importance of the exact local environment of a
      residue in determining its effects on stability.

PMID- 9770482
TI  - Low frequency vibrational modes in proteins: changes induced by point-mutations
      in the protein-cofactor matrix of bacterial reaction centers.
AB  - As a step toward understanding their functional role, the low frequency
      vibrational motions (<300 cm-1) that are coupled to optical excitation of the
      primary donor bacteriochlorophyll cofactors in the reaction center from
      Rhodobacter sphaeroides were investigated. The pattern of hydrogen-bonding
      interaction between these bacteriochlorophylls and the surrounding protein was
      altered in several ways by mutation of single amino acids. The spectrum of low
      frequency vibrational modes identified by femtosecond coherence spectroscopy
      varied strongly between the different reaction center complexes, including
      between different mutants where the pattern of hydrogen bonds was the same. It is
      argued that these variations are primarily due to changes in the nature of the
      individual modes, rather than to changes in the charge distribution in the
      electronic states involved in the optical excitation. Pronounced effects of point
      mutations on the low frequency vibrational modes active in a protein-cofactor
      system have not been reported previously. The changes in frequency observed
      indicate a strong involvement of the protein in these nuclear motions and
      demonstrate that the protein matrix can increase or decrease the fluctuations of
      the cofactor along specific directions.

PMID- 9770483
TI  - PRIM: proximity imaging of green fluorescent protein-tagged polypeptides.
AB  - We report a serendipitous discovery that extends the impressive catalog of
      reporter functions performed by green fluorescent protein (GFP) or its
      derivatives. When two GFP molecules are brought into proximity, changes in the
      relative intensities of green fluorescence emitted upon excitation at 395 vs. 475
      nm result. These spectral changes provide a sensitive ratiometric index of the
      extent of self-association that can be exploited to quantitatively image homo
      oligomerization or clustering processes of GFP-tagged proteins in vivo. The
      method, which we term proximity imaging (PRIM), complements fluorescence
      resonance energy transfer between a blue fluorescent protein donor and a GFP
      acceptor, a powerful method for imaging proximity relationships between different
      proteins. However, unlike fluorescence resonance energy transfer (which is a
      spectral interaction), PRIM depends on direct contact between two GFP modules,
      which can lead to structural perturbations and concomitant spectral changes
      within a module. Moreover, the precise spatial arrangement of the GFP molecules
      within a given dimer determines the magnitude and direction of the spectral
      change. We have used PRIM to detect FK1012-induced dimerization of GFP fused to
      FK506-binding protein and clustering of glycosylphosphatidylinositol-anchored GFP
      at cell surfaces.

PMID- 9770484
TI  - Normal hepatic glucose production in the absence of GLUT2 reveals an alternative
      pathway for glucose release from hepatocytes.
AB  - Glucose production by liver is a major physiological function, which is required
      to prevent development of hypoglycemia in the postprandial and fasted states. The
      mechanism of glucose release from hepatocytes has not been studied in detail but
      was assumed instead to depend on facilitated diffusion through the glucose
      transporter GLUT2. Here, we demonstrate that in the absence of GLUT2 no other
      transporter isoforms were overexpressed in liver and only marginally significant
      facilitated diffusion across the hepatocyte plasma membrane was detectable.
      However, the rate of hepatic glucose output was normal. This was evidenced by (i)
      the hyperglycemic response to i.p. glucagon injection; (ii) the in vivo
      measurement of glucose turnover rate; and (iii) the rate of release of
      neosynthesized glucose from isolated hepatocytes. These observations therefore
      indicated the existence of an alternative pathway for hepatic glucose output.
      Using a [14C]-pyruvate pulse-labeling protocol to quantitate neosynthesis and
      release of [14C]glucose, we demonstrated that this pathway was sensitive to low
      temperature (12 degreesC). It was not inhibited by cytochalasin B nor by the
      intracellular traffic inhibitors brefeldin A and monensin but was blocked by
      progesterone, an inhibitor of cholesterol and caveolae traffic from the
      endoplasmic reticulum to the plasma membrane. Our observations thus demonstrate
      that hepatic glucose release does not require the presence of GLUT2 nor of any
      plasma membrane glucose facilitative diffusion mechanism. This implies the
      existence of an as yet unsuspected pathway for glucose release that may be based
      on a membrane traffic mechanism.

PMID- 9770485
TI  - Regulation of endothelial monocyte-activating polypeptide II release by
      apoptosis.
AB  - Endothelial monocyte-activating polypeptide II (EMAP II) is a proinflammatory
      cytokine and a chemoattractant for monocytes. We show here that, in the mouse
      embryo, EMAP II mRNA was most abundant at sites of tissue remodeling where many
      apoptotic cells could be detected by terminal deoxynucleotidyltransferase
      mediated dUTP end labeling. Removal of dead cells is known to require
      macrophages, and these were found to colocalize with areas of EMAP II mRNA
      expression and programmed cell death. In cultured cells, post-translational
      processing of pro-EMAP II protein to the mature released EMAP II form (23 kDa)
      occurred coincidentally with apoptosis. Cleavage of pro-EMAP II could be
      abrogated in cultured cells by using a peptide-based inhibitor, which competes
      with the ASTD cleavage site of pro-EMAP II. Our results suggest that the
      coordinate program of cell death includes activation of a caspase-like activity
      that initiates the processing of a cytokine responsible for macrophage attraction
      to the sites of apoptosis.

PMID- 9770486
TI  - Subnuclear localization of the active variant surface glycoprotein gene
      expression site in Trypanosoma brucei.
AB  - In Trypanosoma brucei, transcription by RNA polymerase II and 5' capping of
      messenger RNA are uncoupled: a capped spliced leader is trans spliced to every
      RNA. This decoupling makes it possible to have protein-coding gene transcription
      driven by RNA polymerase I. Indeed, indirect evidence suggests that the genes for
      the major surface glycoproteins, variant surface glycoproteins (VSGs) in
      bloodstream-form trypanosomes, are transcribed by RNA polymerase I. In a single
      trypanosome, only one VSG expression site is maximally transcribed at any one
      time, and it has been speculated that transcription takes place at a unique site
      within the nucleus, perhaps in the nucleolus. We tested this by using
      fluorescence in situ hybridization. With probes that cover about 50 kb of the
      active 221 expression site, we detected nuclear transcripts of this site in a
      single fluorescent spot, which did not colocalize with the nucleolus. Analysis of
      marker gene-tagged active expression site DNA by fluorescent DNA in situ
      hybridization confirmed the absence of association with the nucleolus. Even an
      active expression site in which the promoter had been replaced by an rDNA
      promoter did not colocalize with the nulceolus. As expected, marker genes
      inserted in the rDNA array predominantly colocalize with the nucleolus, whereas
      the tubulin gene arrays do not. We conclude that transcription of the active VSG
      expression site does not take place in the nucleolus.

PMID- 9770487
TI  - A DNA damage and stress inducible G protein-coupled receptor blocks cells in
      G2/M.
AB  - Cell cycle progression is monitored by highly coordinated checkpoint machinery,
      which is activated to induce cell cycle arrest until defects like DNA damage are
      corrected. We have isolated an anti-proliferative cell cycle regulator named G2A
      (for G2 accumulation), which is predominantly expressed in immature T and B
      lymphocyte progenitors and is a member of the seven membrane-spanning G protein
      coupled receptor family. G2A overexpression attenuates the transformation
      potential of BCR-ABL and other oncogenes, and leads to accumulation of cells at
      G2/M independently of p53 and c-Abl. G2A can be induced in lymphocytes and to a
      lesser extent in nonlymphocyte cell lines or tissues by multiple stimuli
      including different classes of DNA-damaging agents and serves as a response to
      damage and cellular stimulation which functions to slow cell cycle progression.

PMID- 9770488
TI  - GIPC, a PDZ domain containing protein, interacts specifically with the C terminus
      of RGS-GAIP.
AB  - We have identified a mammalian protein called GIPC (for GAIP interacting protein,
      C terminus), which has a central PDZ domain and a C-terminal acyl carrier protein
      (ACP) domain. The PDZ domain of GIPC specifically interacts with RGS-GAIP, a
      GTPase-activating protein (GAP) for Galphai subunits recently localized on
      clathrin-coated vesicles. Analysis of deletion mutants indicated that the PDZ
      domain of GIPC specifically interacts with the C terminus of GAIP (11 amino
      acids) in the yeast two-hybrid system and glutathione S-transferase (GST)-GIPC
      pull-down assays, but GIPC does not interact with other members of the RGS
      (regulators of G protein signaling) family tested. This finding is in keeping
      with the fact that the C terminus of GAIP is unique and possesses a modified C
      terminal PDZ-binding motif (SEA). By immunoblotting of membrane fractions
      prepared from HeLa cells, we found that there are two pools of GIPC-a soluble or
      cytosolic pool (70%) and a membrane-associated pool (30%). By immunofluorescence,
      endogenous and GFP-tagged GIPC show both a diffuse and punctate cytoplasmic
      distribution in HeLa cells reflecting, respectively, the existence of soluble and
      membrane-associated pools. By immunoelectron microscopy the membrane pool of GIPC
      is associated with clusters of vesicles located near the plasma membrane. These
      data provide direct evidence that the C terminus of a RGS protein is involved in
      interactions specific for a given RGS protein and implicates GAIP in regulation
      of additional functions besides its GAP activity. The location of GIPC together
      with its binding to GAIP suggest that GAIP and GIPC may be components of a G
      protein-coupled signaling complex involved in the regulation of vesicular
      trafficking. The presence of an ACP domain suggests a putative function for GIPC
      in the acylation of vesicle-bound proteins.

PMID- 9770489
TI  - Phospholipase D activity is required for suppression of yeast
      phosphatidylinositol transfer protein defects.
AB  - Yeast phosphatidylinositol transfer protein (Sec14p) function is essential for
      production of Golgi-derived secretory vesicles, and this requirement is bypassed
      by mutations in at least seven genes. Analyses of such 'bypass Sec14p' mutants
      suggest that Sec14p acts to maintain an essential Golgi membrane diacylglycerol
      (DAG) pool that somehow acts to promote Golgi secretory function. SPO14 encodes
      the sole yeast phosphatidylinositol-4,5-bisphosphate-activated phospholipase D
      (PLD). PLD function, while essential for meiosis, is dispensable for vegetative
      growth. Herein, we report specific physiological circumstances under which an
      unanticipated requirement for PLD activity in yeast vegetative Golgi secretory
      function is revealed. This PLD involvement is essential in 'bypass Sec14p'
      mutants where normally Sec14p-dependent Golgi secretory reactions are occurring
      in a Sec14p-independent manner. PLD catalytic activity is necessary but not
      sufficient for 'bypass Sec14p', and yeast operating under 'bypass Sec14p'
      conditions are ethanol-sensitive. These data suggest that PLD supports 'bypass
      Sec14p' by generating a phosphatidic acid pool that is somehow utilized in
      supporting yeast Golgi secretory function.

PMID- 9770491
TI  - Inhibition of myogenesis by transforming growth factor beta is density-dependent
      and related to the translocation of transcription factor MEF2 to the cytoplasm.
AB  - Transforming growth factor beta (TGF-beta) was found to inhibit differentiation
      of myogenic cells only when they were grown to high density. Inhibition also
      occurred when myogenic cells were cocultured with other types of mesenchymal
      cells but not when they were cocultured with epithelial cells. It is therefore
      possible that some density-dependent signaling mediates the intracellular
      response to TGF-beta. Within 30 min of treatment, TGF-beta induced translocation
      of MEF2, but not MyoD, myogenin, or p21, to the cytoplasm of myogenic cells grown
      to high density. Translocation was reversible on withdrawal of TGF-beta. By using
      immune electron microscopy and Western blot analysis on subcellular fractions,
      MEF2 was shown to be tightly associated with cytoskeleton membrane components. To
      test whether MEF2 export from the nucleus was causally related to the inhibitory
      action of TGF-beta, we transfected C2C12 myoblasts with MEF2C containing the
      nuclear localization signal of simian virus 40 large T antigen (nlsSV40).
      Myogenic cells expressing the chimerical MEF2C/nlsSV40, but not wild-type MEF2C,
      retained this transcription factor in the nucleus and were resistant to the
      inhibitory action of TGF-beta. We propose a mechanism in which the inhibition of
      myogenesis by TGF-beta is mediated through MEF2 localization to the cytoplasm,
      thus preventing it from participating in an active transcriptional complex.

PMID- 9770490
TI  - Nuclear-encoded proteins target to the plastid in Toxoplasma gondii and
      Plasmodium falciparum.
AB  - A vestigial, nonphotosynthetic plastid has been identified recently in protozoan
      parasites of the phylum Apicomplexa. The apicomplexan plastid, or "apicoplast,"
      is indispensable, but the complete sequence of both the Plasmodium falciparum and
      Toxoplasma gondii apicoplast genomes has offered no clue as to what essential
      metabolic function(s) this organelle might perform in parasites. To investigate
      possible functions of the apicoplast, we sought to identify nuclear-encoded genes
      whose products are targeted to the apicoplast in Plasmodium and Toxoplasma. We
      describe here nuclear genes encoding ribosomal proteins S9 and L28 and the fatty
      acid biosynthetic enzymes acyl carrier protein (ACP), beta-ketoacyl-ACP synthase
      III (FabH), and beta-hydroxyacyl-ACP dehydratase (FabZ). These genes show high
      similarity to plastid homologues, and immunolocalization of S9 and ACP verifies
      that the proteins accumulate in the plastid. All the putatively apicoplast
      targeted proteins bear N-terminal presequences consistent with plastid targeting,
      and the ACP presequence is shown to be sufficient to target a recombinant green
      fluorescent protein reporter to the apicoplast in transgenic T. gondii.
      Localization of ACP, and very probably FabH and FabZ, in the apicoplast
      implicates fatty acid biosynthesis as a likely function of the apicoplast.
      Moreover, inhibition of P. falciparum growth by thiolactomycin, an inhibitor of
      FabH, indicates a vital role for apicoplast fatty acid biosynthesis. Because the
      fatty acid biosynthesis genes identified here are of a plastid/bacterial type,
      and distinct from those of the equivalent pathway in animals, fatty acid
      biosynthesis is potentially an excellent target for therapeutics directed against
      malaria, toxoplasmosis, and other apicomplexan-mediated diseases.

PMID- 9770492
TI  - Isolation and characterization of mammalian homologs of the Drosophila gene glial
      cells missing.
AB  - The glial cells missing (gcm) gene in Drosophila encodes a transcription factor
      that determines the choice between glial and neuronal fates. We report here the
      isolation of two mammalian gcm homologs, Gcm1 and Gcm2, and the characterization
      of their expression patterns during embryonic development. Although Gcm2 is
      expressed in neural tissues at a low level, the major sites of expression for
      both of the mammalian genes are nonneural, suggesting that the functions of the
      mammalian homologs have diverged and diversified. However, when expressed
      ectopically, Gcm1 can substitute functionally for Drosophila gcm by transforming
      presumptive neurons into glia. Thus, certain biochemical properties, although not
      the specificity of the tissue in which the gene is expressed, have been conserved
      through the evolution of the Gcm gene family.

PMID- 9770493
TI  - Delayed embryonic lethality in mice lacking protein phosphatase 2A catalytic
      subunit Calpha.
AB  - Protein phosphatase 2A (PP2A) is a multimeric enzyme, containing a catalytic
      subunit complexed with two regulatory subunits. The catalytic subunit PP2A C is
      encoded by two distinct and unlinked genes, termed Calpha and Cbeta. The specific
      function of these two catalytic subunits is unknown. To address the possible
      redundancy between PP2A and related phosphatases as well as between Calpha and
      Cbeta, the Calpha subunit gene was deleted by homologous recombination.
      Homozygous null mutant mice are embryonically lethal, demonstrating that the
      Calpha subunit gene is an essential gene. As PP2A exerts a range of cellular
      functions including cell cycle regulation and cell fate determination, we were
      surprised to find that these embryos develop normally until postimplantation,
      around embryonic day 5.5/6.0. While no Calpha protein is expressed, we find
      comparable expression levels of PP2A C at a time when the embryo is degenerating.
      Despite a 97% amino acid identity, Cbeta cannot completely compensate for the
      absence of Calpha. Degenerated embryos can be recovered even at embryonic day
      13.5, indicating that although embryonic tissue is still capable of
      proliferating, normal differentiation is significantly impaired. While the
      primary germ layers ectoderm and endoderm are formed, mesoderm is not formed in
      degenerating embryos.

PMID- 9770494
TI  - Loss of social behaviors by myxococcus xanthus during evolution in an
      unstructured habitat.
AB  - Social behaviors are often targets of natural selection among higher organisms,
      but quantifying the effects of such selection is difficult. We have used the
      bacterium Myxococcus xanthus as a model system for studying the evolution of
      social interactions. Changes in the social behaviors of 12 M. xanthus populations
      were quantified after 1,000 generations of evolution in a liquid habitat, in
      which interactions among individuals were continually hindered by shaking and low
      cell densities. Derived lineages were compared with their ancestors with respect
      to maximum growth rate, motility rates on hard and soft agar, fruiting body
      formation ability, and sporulation frequency during starvation. Improved
      performance in the liquid selective regime among evolved lines was usually
      associated with significant reductions in all of the major social behaviors of M.
      xanthus. Maintenance of functional social behaviors is apparently detrimental to
      fitness under asocial growth conditions.

PMID- 9770495
TI  - Natural genetic exchange between Haemophilus and Neisseria: intergeneric transfer
      of chromosomal genes between major human pathogens.
AB  - Members of the bacterial families Haemophilus and Neisseria, important human
      pathogens that commonly colonize the nasopharynx, are naturally competent for DNA
      uptake from their environment. In each genus this process is discriminant in
      favor of its own and against foreign DNA through sequence specificity of DNA
      receptors. The Haemophilus DNA uptake apparatus binds a 29-bp oligonucleotide
      domain containing a highly conserved 9-bp core sequence, whereas the neisserial
      apparatus binds a 10-bp motif. Each motif ("uptake sequence", US) is highly over
      represented in the chromosome of the corresponding genus, particularly
      concentrated with core sequences in inverted pairs forming gene terminators. Two
      Haemophilus core USs were unexpectedly found forming the terminator of sodC in
      Neisseria meningitidis (meningococcus), and sequence analysis strongly suggests
      that this virulence gene, located next to IS1106, arose through horizontal
      transfer from Haemophilus. By using USs as search strings in a computer-based
      analysis of genome sequence, it was established that while USs of the "wrong"
      genus do not occur commonly in Neisseria or Haemophilus, where they do they are
      highly likely to flag domains of chromosomal DNA that have been transferred from
      Haemophilus. Three independent domains of Haemophilus-like DNA were found in the
      meningococcal chromosome, associated respectively with the virulence gene sodC,
      the bio gene cluster, and an unidentified orf. This report identifies
      intergenerically transferred DNA and its source in bacteria, and further
      identifies transformation with heterologous chromosomal DNA as a way of
      establishing potentially important chromosomal mosaicism in these pathogenic
      bacteria.

PMID- 9770496
TI  - Testing the Cambrian explosion hypothesis by using a molecular dating technique.
AB  - Molecular studies have the potential to shed light on the origin of the animal
      phyla by providing independent estimates of the divergence times, but have been
      criticized for failing to account adequately for variation in rate of evolution.
      A method of dating divergence times from molecular data addresses the criticisms
      of earlier studies and provides more realistic, but wider, confidence intervals.
      The data are not compatible with the Cambrian explosion hypothesis as an
      explanation for the origin of metazoan phyla, and provide additional support for
      an extended period of Precambrian metazoan diversification.

PMID- 9770497
TI  - The optimization principle in phylogenetic analysis tends to give incorrect
      topologies when the number of nucleotides or amino acids used is small.
AB  - In the maximum parsimony (MP) and minimum evolution (ME) methods of phylogenetic
      inference, evolutionary trees are constructed by searching for the topology that
      shows the minimum number of mutational changes required (M) and the smallest sum
      of branch lengths (S), respectively, whereas in the maximum likelihood (ML)
      method the topology showing the highest maximum likelihood (A) of observing a
      given data set is chosen. However, the theoretical basis of the optimization
      principle remains unclear. We therefore examined the relationships of M, S, and A
      for the MP, ME, and ML trees with those for the true tree by using computer
      simulation. The results show that M and S are generally greater for the true tree
      than for the MP and ME trees when the number of nucleotides examined (n) is
      relatively small, whereas A is generally lower for the true tree than for the ML
      tree. This finding indicates that the optimization principle tends to give
      incorrect topologies when n is small. To deal with this disturbing property of
      the optimization principle, we suggest that more attention should be given to
      testing the statistical reliability of an estimated tree rather than to finding
      the optimal tree with excessive efforts. When a reliability test is conducted,
      simplified MP, ME, and ML algorithms such as the neighbor-joining method
      generally give conclusions about phylogenetic inference very similar to those
      obtained by the more extensive tree search algorithms.

PMID- 9770499
TI  - The Saccharomyces cerevisiae MLH3 gene functions in MSH3-dependent suppression of
      frameshift mutations.
AB  - The Saccharomyces cerevisiae genome encodes four MutL homologs. Of these, MLH1
      and PMS1 are known to act in the MSH2-dependent pathway that repairs DNA
      mismatches. We have investigated the role of MLH3 in mismatch repair. Mutations
      in MLH3 increased the rate of reversion of the hom3-10 allele by increasing the
      rate of deletion of a single T in a run of 7 Ts. Combination of mutations in MLH3
      and MSH6 caused a synergistic increase in the hom3-10 reversion rate, whereas the
      hom3-10 reversion rate in an mlh3 msh3 double mutant was the same as in the
      respective single mutants. Similar results were observed when the accumulation of
      mutations at frameshift hot spots in the LYS2 gene was analyzed, although
      mutation of MLH3 did not cause the same extent of affect at every LYS2 frameshift
      hot spot. MLH3 interacted with MLH1 in a two-hybrid system. These data are
      consistent with the idea that a proportion of the repair of specific
      insertion/deletion mispairs by the MSH3-dependent mismatch repair pathway uses a
      heterodimeric MLH1-MLH3 complex in place of the MLH1-PMS1 complex.

PMID- 9770498
TI  - Evidence for balancing selection operating at the het-c heterokaryon
      incompatibility locus in a group of filamentous fungi.
AB  - In filamentous fungi, het loci (for heterokaryon incompatibility) are believed to
      regulate self/nonself-recognition during vegetative growth. As filamentous fungi
      grow, hyphal fusion occurs within an individual colony to form a network. Hyphal
      fusion can occur also between different individuals to form a heterokaryon, in
      which genetically distinct nuclei occupy a common cytoplasm. However,
      heterokaryotic cells are viable only if the individuals involved have identical
      alleles at all het loci. One het locus, het-c, has been characterized at the
      molecular level in Neurospora crassa and encodes a glycine-rich protein. In an
      effort to understand the role of this locus in filamentous fungi, we chose to
      study its evolution by analyzing het-c sequence variability in species within
      Neurospora and related genera. We determined that the het-c locus was polymorphic
      in a field population of N. crassa with close to equal frequency of each of the
      three allelic types. Different species and even genera within the Sordariaceae
      shared het-c polymorphisms, indicating that these polymorphisms originated in an
      ancestral species. Finally, an analysis of the het-c specificity region shows a
      high occurrence of nonsynonymous substitution. The persistence of allelic
      lineages, the nearly equal allelic distribution within populations, and the high
      frequency of nonsynonymous substitutions in the het-c specificity region suggest
      that balancing selection has operated to maintain allelic diversity at het-c. Het
      c shares this particular evolutionary characteristic of departing from neutrality
      with other self/nonself-recognition systems such as major histocompatibility
      complex loci in mammals and the S (self-incompatibility) locus in angiosperms.

PMID- 9770500
TI  - A novel amplicon at 8p22-23 results in overexpression of cathepsin B in
      esophageal adenocarcinoma.
AB  - Cathepsin B (CTSB) is overexpressed in tumors of the lung, prostate, colon,
      breast, and stomach. However, evidence of primary genomic alterations in the CTSB
      gene during tumor initiation or progression has been lacking. We have found a
      novel amplicon at 8p22-23 that results in CTSB overexpression in esophageal
      adenocarcinoma. Amplified genomic NotI-HinfI fragments were identified by two
      dimensional DNA electrophoresis. Two amplified fragments (D4 and D5) were cloned
      and yielded unique sequences. Using bacterial artificial chromosome clones
      containing either D4 or D5, fluorescent in situ hybridization defined a single
      region of amplification involving chromosome bands 8p22-23. We investigated the
      candidate cancer-related gene CTSB, and potential coamplified genes from this
      region including farnesyl-diphosphate farnesyltransferase (FDFT1), arylamine N
      acetyltransferase (NAT-1), lipoprotein lipase (LPL), and an uncharacterized
      expressed sequence tag (D8S503). Southern blot analysis of 66 esophageal
      adenocarcinomas demonstrated only CTSB and FDFT1 were consistently amplified in
      eight (12.1%) of the tumors. Neither NAT-1 nor LPL were amplified. Northern blot
      analysis showed overexpression of CTSB and FDFT1 mRNA in all six of the amplified
      esophageal adenocarcinomas analyzed. CTSB mRNA overexpression also was present in
      two of six nonamplified tumors analyzed. However, FDFT1 mRNA overexpression
      without amplification was not observed. Western blot analysis confirmed CTSB
      protein overexpression in tumor specimens with CTSB mRNA overexpression compared
      with either normal controls or tumors without mRNA overexpression. Abundant
      extracellular expression of CTSB protein was found in 29 of 40 (72. 5%) of
      esophageal adenocarcinoma specimens by using immunohistochemical analysis. The
      finding of an amplicon at 8p22-23 resulting in CTSB gene amplification and
      overexpression supports an important role for CTSB in esophageal adenocarcinoma
      and possibly in other tumors.

PMID- 9770501
TI  - Linkage disequilibrium mapping in isolated populations: the example of Finland
      revisited.
AB  - Linkage disequilibrium analysis can provide high resolution in the mapping of
      disease genes because it incorporates information on recombinations that have
      occurred during the entire period from the mutational event to the present. A
      circumstance particularly favorable for high-resolution mapping is when a single
      founding mutation segregates in an isolated population. We review here the
      population structure of Finland in which a small founder population some 100
      generations ago has expanded into 5.1 million people today. Among the 30-odd
      autosomal recessive disorders that are more prevalent in Finland than elsewhere,
      several appear to have segregated for this entire period in the "panmictic"
      southern Finnish population. Linkage disequilibrium analysis has allowed precise
      mapping and determination of genetic distances at the 0.1-cM level in several of
      these disorders. Estimates of genetic distance have proven accurate, but previous
      calculations of the confidence intervals were too small because sampling
      variation was ignored. In the north and east of Finland the population can be
      viewed as having been "founded" only after 1500. Disease mutations that have
      undergone such a founding bottleneck only 20 or so generations ago exhibit
      linkage disequilibrium and haplotype sharing over long genetic distances (5-15
      cM). These features have been successfully exploited in the mapping and cloning
      of many genes. We review the statistical issues of fine mapping by linkage
      disequilibrium and suggest that improved methodologies may be necessary to map
      diseases of complex etiology that may have arisen from multiple founding
      mutations.

PMID- 9770503
TI  - Knock-out mutants from an En-1 mutagenized Arabidopsis thaliana population
      generate phenylpropanoid biosynthesis phenotypes.
AB  - A collection of 8,000 Arabidopsis thaliana plants carrying 48,000 insertions of
      the maize transposable element En-1 has been generated. This population was used
      for reverse genetic analyses to identify insertions in individual gene loci. By
      using a PCR-based screening protocol, insertions were found in 55 genes. En-1
      showed no preference for transcribed or untranscribed regions nor for a
      particular orientation relative to the gene of interest. In several cases, En-1
      was inserted within a few kilobases upstream or downstream of the gene. En-1 was
      mobilized from such positions into the respective gene to cause gene disruption.
      Knock-out alleles of genes involved in flavonoid biosynthesis were generated. One
      mutant line contained an En-1 insertion in the flavonol synthase gene (FLS) and
      showed drastically reduced levels of kaempferol. Allelism tests with other lines
      containing En-1 insertions in the flavanone 3-hydroxylase gene (F3H) demonstrated
      that TRANSPARENT TESTA 6 (TT6) encodes flavanone 3-hydroxylase. The f3h and fls
      null mutants complete the set of A. thaliana lines defective in early steps of
      the flavonoid pathway. These experiments demonstrate the efficiency of the
      screening method and gene disruption strategy used for assigning functions to
      genes defined only by sequence.

PMID- 9770504
TI  - Orientation-dependent and sequence-specific expansions of CTG/CAG trinucleotide
      repeats in Saccharomyces cerevisiae.
AB  - A quantitative and selective genetic assay was developed to monitor expansions of
      trinucleotide repeats (TNRs) in yeast. A promoter containing 25 repeats allows
      expression of a URA3 reporter gene and yields sensitivity to the drug 5
      fluoroorotic acid. Expansion of the TNR to 30 or more repeats turns off URA3 and
      provides drug resistance. When integrated at either of two chromosomal loci,
      expansion rates were 1 x 10(-5) to 4 x 10(-5) per generation if CTG repeats were
      replicated on the lagging daughter strand. PCR analysis indicated that 5-28
      additional repeats were present in 95% of the expanded alleles. No significant
      changes in CTG expansion rates occurred in strains deficient in the mismatch
      repair gene MSH2 or the recombination gene RAD52. The frequent nature of CTG
      expansions suggests that the threshold number for this repeat is below 25 in this
      system. In contrast, expansions of the complementary repeat CAG occurred at 500-
      to 1,000-fold lower rates, similar to a randomized (C,A,G) control sequence. When
      the reporter plasmid was inverted within the chromosome, switching the leading
      and lagging strands of replication, frequent expansions were observed only when
      CTG repeats resided on the lagging daughter strand. Among the rare CAG
      expansions, the largest gain in tract size was 38 repeats. The control repeats
      CTA and TAG showed no detectable rate of expansions. The orientation-dependence
      and sequence-specificity data support the model that expansions of CTG and CAG
      tracts result from aberrant DNA replication via hairpin-containing Okazaki
      fragments.

PMID- 9770502
TI  - Apoptosis regulator bcl-w is essential for spermatogenesis but appears otherwise
      redundant.
AB  - Proteins of the Bcl-2 family are important regulators of apoptosis in many
      tissues of the embryo and adult. The recently isolated bcl-w gene encodes a pro
      survival member of the Bcl-2 family, which is widely expressed. To explore its
      physiological role, we have inactivated the bcl-w gene in the mouse by homologous
      recombination. Mice that lack Bcl-w were viable, healthy, and normal in
      appearance. Most tissues exhibited typical histology, and hematopoiesis was
      unaffected, presumably due to redundant function with other pro-survival family
      members. Although female reproductive function was normal, the males were
      infertile. The testes developed normally, and the initial, prepubertal wave of
      spermatogenesis was largely unaffected. The seminiferous tubules of adult males,
      however, were disorganized, contained numerous apoptotic cells, and produced no
      mature sperm. Both Sertoli cells and germ cells of all types were reduced in
      number, the most mature germ cells being the most severely depleted. The bcl-w-/-
      mouse provides a unique model of failed spermatogenesis in the adult that may be
      relevant to some cases of human male sterility.

PMID- 9770505
TI  - Cloning of inversion breakpoints in the Anopheles gambiae complex traces a
      transposable element at the inversion junction.
AB  - Anopheles arabiensis, one of the two most potent malaria vectors of the gambiae
      complex, is characterized by the presence of chromosomal paracentric inversions.
      Elucidation of the nature and the dynamics of these inversions is of paramount
      importance for the understanding of the population genetics and evolutionary
      biology of this mosquito and of the impact on malaria epidemiology. We report
      here the cloning of the breakpoints of the naturally occurring polymorphic
      inversion 2Rd' of A. arabiensis. A cDNA clone that cytologically mapped on the
      proximal breakpoint was the starting material for the isolation of a cosmid clone
      that spanned the breakpoint. Analysis of the surrounding sequences demonstrated
      that adjacent to the distal breakpoint lies a repetitive element that exhibits
      distinct distribution in different A. arabiensis strains. Sequencing analysis of
      that area revealed elements characteristic of transposable element terminal
      repeats. We called this presumed transposable element Odysseus. The presence of
      Odysseus at the junction of the naturally occuring inversion 2Rd' suggests that
      the inversion may be the result of the transposable element's activity.
      Characteristics of Odysseus' terminal region as well as its cytological
      distribution in different strains may indicate a relatively recent activity of
      Odysseus.

PMID- 9770506
TI  - Discrimination of the closely related A and D genomes of the hexaploid oat Avena
      sativa L.
AB  - A satellite DNA sequence, As120a, specific to the A-genome chromosomes in the
      hexaploid oat, Avena sativa L., was isolated by subcloning a fragment with
      internal tandem repeats from a plasmid, pAs120, that had been obtained from an
      Avena strigosa (As genome) genomic library. Southern and in situ hybridization
      showed that sequences with homology to sequences within pAs120 were dispersed
      throughout the genome of diploid (A and C genomes), tetraploid (AC genomes), and
      hexaploid (ACD genomes) Avena species. In contrast, sequences homologous to
      As120a were found in two A-genome species (A. strigosa and Avena longiglumis) and
      in the hexaploid A. sativa whereas this sequence was little amplified in the
      tetraploid Avena murphyi and was absent in the remaining A- and C-genome diploid
      species. In situ hybridization of pAs120a to hexaploid oat species revealed the
      distribution of elements of the As120a repeated family over both arms of 14 of 42
      chromosomes of this species. By using double in situ hybridization with pAs120a
      and a C genome-specific probe, three sets of 14 chromosomes were revealed
      corresponding to the A, C, and D genomes of the hexaploid species. Simultaneous
      in situ hybridizations with pAs120a and ribosomal probes were used to assign the
      SAT chromosomes of hexaploid species to their correct genomes. This work reports
      a sequence able to distinguish between the closely related A and D genomes of
      hexaploid oats. This sequence offers new opportunities to analyze the
      relationships of Avena species and to explore the possible evolution of various
      polyploid oat species.

PMID- 9770507
TI  - Riboregulation in Escherichia coli: DsrA RNA acts by RNA:RNA interactions at
      multiple loci.
AB  - DsrA is an 87-nt untranslated RNA that regulates both the global transcriptional
      silencer and nucleoid protein H-NS and the stationary phase and stress response
      sigma factor RpoS (sigmas). We demonstrate that DsrA acts via specific RNA:RNA
      base pairing interactions at the hns locus to antagonize H-NS translation. We
      also give evidence that supports a role for RNA:RNA interactions at the rpoS
      locus to enhance RpoS translation. Negative regulation of hns by DsrA is achieved
      by the RNA:RNA interaction blocking translation of hns RNA. In contrast, results
      suggest that positive regulation of rpoS by DsrA occurs by formation of an RNA
      structure that activates a cis-acting translational operator. Sequences within
      DsrA complementary to three additional genes, argR, ilvIH, and rbsD, suggest that
      DsrA is a riboregulator of gene expression that acts coordinately via RNA:RNA
      interactions at multiple loci.

PMID- 9770508
TI  - DsrA RNA regulates translation of RpoS message by an anti-antisense mechanism,
      independent of its action as an antisilencer of transcription.
AB  - DsrA RNA regulates both transcription, by overcoming transcriptional silencing by
      the nucleoid-associated H-NS protein, and translation, by promoting efficient
      translation of the stress sigma factor, RpoS. These two activities of DsrA can be
      separated by mutation: the first of three stem-loops of the 85 nucleotide RNA is
      necessary for RpoS translation but not for anti-H-NS action, while the second
      stem-loop is essential for antisilencing and less critical for RpoS translation.
      The third stem-loop, which behaves as a transcription terminator, can be
      substituted by the trp transcription terminator without loss of either DsrA
      function. The sequence of the first stem-loop of DsrA is complementary with the
      upstream leader portion of rpoS messenger RNA, suggesting that pairing of DsrA
      with the rpoS message might be important for translational regulation. Mutations
      in the Rpos leader and compensating mutations in DsrA confirm that this predicted
      pairing is necessary for DsrA stimulation of RpoS translation. We propose that
      DsrA pairing stimulates RpoS translation by acting as an anti-antisense RNA,
      freeing the translation initiation region from the cis-acting antisense RNA and
      allowing increased translation.

PMID- 9770509
TI  - Induction of microsatellite instability by oxidative DNA damage.
AB  - Instability of repetitive sequences, both in intronic sequences and within coding
      regions, has been demonstrated to be a hallmark of genomic instability in human
      cancer. Understanding how these mutational events arise may provide an
      opportunity for prevention or early intervention in cancer development. To study
      the source of this instability, we have identified a region of the beta-lactamase
      gene that is tolerant to the insertion of fragments of exogenous DNA as large as
      1,614 bp with minimal loss of enzyme activity, as determined by antibiotic
      resistance. Fragments inserted out-of-frame render Escherichia coli sensitive to
      antibiotic, and compensatory frameshift mutations that restore the reading frame
      of beta-lactamase can be selected on the basis of antibiotic resistance. We have
      utilized this site to insert a synthetic microsatellite sequence within the beta
      lactamase gene and selected for mutations yielding frameshifts. This assay
      provides for detection of one frameshift mutation in a background of 10(6) wild
      type sequences. Mismatch repair deficiency increased the observed frameshift
      frequency approximately 300-fold. Exposure of plasmid containing microsatellite
      sequences to hydrogen peroxide resulted in frameshift mutations that were
      localized exclusively to the microsatellite sequences, whereas DNA damage by UV
      or N-methyl-N'-nitro-N-nitrosoguanidine did not result in enhanced mutagenesis.
      We postulate that in tumor cells, endogenous production of oxygen free radicals
      may be a major factor in promoting instability of microsatellite sequences. This
      beta-lactamase assay may provide a sensitive methodology for the detection and
      quantitation of mutations associated with the development of cancer.

PMID- 9770510
TI  - A novel multicomponent regulatory system mediates H2 sensing in Alcaligenes
      eutrophus.
AB  - Oxidation of molecular hydrogen catalyzed by [NiFe] hydrogenases is a widespread
      mechanism of energy generation among prokaryotes. Biosynthesis of the H2
      oxidizing enzymes is a complex process subject to positive control by H2 and
      negative control by organic energy sources. In this report we describe a novel
      signal transduction system regulating hydrogenase gene (hox) expression in the
      proteobacterium Alcaligenes eutrophus. This multicomponent system consists of the
      proteins HoxB, HoxC, HoxJ*, and HoxA. HoxB and HoxC share characteristic features
      of dimeric [NiFe] hydrogenases and form the putative H2 receptor that interacts
      directly or indirectly with the histidine protein kinase HoxJ*. A single amino
      acid substitution (HoxJ*G422S) in a conserved C-terminal glycine-rich motif of
      HoxJ* resulted in a loss of H2-dependent signal transduction and a concomitant
      block in autophosphorylating activity, suggesting that autokinase activity is
      essential for the response to H2. Whereas deletions in hoxB or hoxC abolished
      hydrogenase synthesis almost completely, the autokinase-deficient strain
      maintained high-level hox gene expression, indicating that the active sensor
      kinase exerts a negative effect on hox gene expression in the absence of H2.
      Substitutions of the conserved phosphoryl acceptor residue Asp55 in the response
      regulator HoxA (HoxAD55E and HoxAD55N) disrupted the H2 signal-transduction
      chain. Unlike other NtrC-like regulators, the altered HoxA proteins still allowed
      high-level transcriptional activation. The data presented here suggest a model in
      which the nonphosphorylated form of HoxA stimulates transcription in concert with
      a yet unknown global energy-responsive factor.

PMID- 9770511
TI  - Resistance to DNA fragmentation and chromatin condensation in mice lacking the
      DNA fragmentation factor 45.
AB  - The DNA fragmentation factor 45 (DFF45) is a subunit of a heterodimeric nuclease
      complex critical for the induction of DNA fragmentation in vitro. To understand
      the in vivo role of DFF45 in programmed cell death, we generated DFF45 mutant
      mice. DNA fragmentation activity is completely abolished in cell extracts from
      DFF45 mutant tissues. In response to apoptotic stimuli, splenocytes, thymocytes,
      and granulocytes from DFF45 mutant mice are resistant to DNA fragmentation, and
      splenocytes and thymocytes are also resistant to chromatin condensation.
      Nevertheless, development of the immune system in the DFF45 mutant mice is
      normal. These results demonstrate that DFF45 is critical for the induction of DNA
      fragmentation and chromatin condensation in vivo, but is not required for normal
      immune system development.

PMID- 9770512
TI  - Rap1 protein regulates telomere turnover in yeast.
AB  - Telomere length is maintained through a dynamic balance between addition and loss
      of the terminal telomeric DNA. Normal telomere length regulation requires
      telomerase as well as a telomeric protein-DNA complex. Previous work has provided
      evidence that in the budding yeasts Kluyveromyces lactis and Saccharomyces
      cerevisiae, the telomeric double-stranded DNA binding protein Rap1p negatively
      regulates telomere length, in part by nucleating, by its C-terminal tail, a
      higher-order DNA binding protein complex that presumably limits access of
      telomerase to the chromosome end. Here we show that in K. lactis, truncating the
      Rap1p C-terminal tail (Rap1p-DeltaC mutant) accelerates telomeric repeat turnover
      in the distal region of the telomere. In addition, combining the rap1-DeltaC
      mutation with a telomerase template mutation (ter1-kpn), which directs the
      addition of mutated telomeric DNA repeats to telomeres, synergistically caused an
      immediate loss of telomere length regulation. Capping of the unregulated
      telomeres of these double mutants with functionally wild-type repeats restored
      telomere length control. We propose that the rate of terminal telomere turnover
      is controlled by Rap1p specifically through its interactions with the most distal
      telomeric repeats.

PMID- 9770513
TI  - Major histocompatibility complex (MHC) class I KbDb -/- deficient mice possess
      functional CD8+ T cells and natural killer cells.
AB  - We obtained mice deficient for major histocompatibility complex (MHC) molecules
      encoded by the H-2K and H-2D genes. H-2 KbDb -/- mice express no detectable
      classical MHC class I-region associated (Ia) heavy chains, although beta2
      microglobulin and the nonclassical class Ib proteins examined are expressed
      normally. KbDb -/- mice have greatly reduced numbers of mature CD8+ T cells,
      indicating that selection of the vast majority (>90%) of CD8+ T cells cannot be
      compensated for by beta2-microglobulin-associated molecules other than classical
      H-2K and D locus products. In accord with the greatly reduced number of CD8+ T
      cells, spleen cells from KbDb -/- mice do not generate cytotoxic responses in
      primary mixed-lymphocyte cultures against MHC-disparate (allogeneic) cells.
      However, in vivo priming of KbDb -/- mice with allogeneic cells resulted in
      strong CD8+ MHC class Ia-specific allogeneic responses. Thus, a minor population
      of functionally competent peripheral CD8+ T cells capable of strong cytotoxic
      activity arises in the complete absence of classical MHC class Ia molecules. KbDb
      -/- animals also have natural killer cells that retain their cytotoxic potential.

PMID- 9770514
TI  - Cell-cycle arrest and apoptosis hypersusceptibility as a consequence of Lck
      deficiency in nontransformed T lymphocytes.
AB  - By using antisense RNA, Lck-deficient transfectants of a T helper 2 (Th2) clone
      have been derived and shown to have a qualitative defect in the T cell receptor
      signaling pathway. A striking feature observed only in Lck-deficient T cells was
      the presence of a constitutively tyrosine-phosphorylated 32-kDa protein. In the
      present study, we provide evidence that this aberrantly hyperphosphorylated
      protein is p34(cdc2) (cdc2) a key regulator of cell-cycle progression. Lck
      deficient transfectants expressed high levels of cdc2 protein and its regulatory
      units, cyclins A and B. The majority of cdc2, however, was tyrosine
      phosphorylated and therefore enzymatically inactive. The transfectants were
      significantly larger than the parental cells and contained 4N DNA. These results
      establish that a deficiency in Lck leads to a cell-cycle arrest in G2. Moreover,
      transfected cells were hypersusceptible to apoptosis when activated through the T
      cell receptor. Importantly, however, this hypersusceptibility was largely
      reversed in the presence of T cell growth factors. These findings provide
      evidence that, in mature T lymphocytes, cell-cycle progression through the G2-M
      check point requires expression of the Src-family protein tyrosine kinase, Lck.
      This requirement is Lck-specific; it is observed under conditions in which the
      closely related Fyn kinase is expressed normally, evincing against a redundancy
      of function between these two kinases.

PMID- 9770515
TI  - Cleavage motifs of the yeast 20S proteasome beta subunits deduced from digests of
      enolase 1.
AB  - The 436-amino acid protein enolase 1 from yeast was degraded in vitro by purified
      wild-type and mutant yeast 20S proteasome particles. Analysis of the cleavage
      products at different times revealed a processive degradation mechanism and a
      length distribution of fragments ranging from 3 to 25 amino acids with an average
      length of 7 to 8 amino acids. Surprisingly, the average fragment length was very
      similar between wild-type and mutant 20S proteasomes with reduced numbers of
      active sites. This implies that the fragment length is not influenced by the
      distance between the active sites, as previously postulated. A detailed analysis
      of the cleavages also allowed the identification of certain amino acid
      characteristics in positions flanking the cleavage site that guide the selection
      of the P1 residues by the three active beta subunits. Because yeast and mammalian
      proteasomes are highly homologous, similar cleavage motifs might be used by
      mammalian proteasomes. Therefore, our data provide a basis for predicting
      proteasomal degradation products from which peptides are sampled by major
      histocompatibility complex class I molecules for presentation to cytotoxic T
      cells.

PMID- 9770516
TI  - Diversification, expression, and gamma delta T cell recognition of evolutionarily
      distant members of the MIC family of major histocompatibility complex class I
      related molecules.
AB  - Distant relatives of major histocompatibility complex (MHC) class I molecules,
      human MICA and MICB, function as stress-induced antigens that are broadly
      recognized by intestinal epithelial gamma delta T cells. They may thus play a
      central role in the immune surveillance of damaged, infected, or otherwise
      stressed intestinal epithelial cells. However, the generality of this system in
      evolution and the mode of recognition of MICA and MICB are undefined. Analysis of
      cDNA sequences from various primate species defined translation products that are
      homologous to MICA and MICB. All of the MIC polypeptides have common
      characteristics, although they are extraordinarily diverse. The most notable
      alterations are several deletions and frequent amino acid substitutions in the
      putative alpha-helical regions of the alpha1 alpha2 domains. However, the primate
      MIC molecules were expressed on the surfaces of normal and transfected cells.
      Moreover, despite their sharing of relatively few identical amino acids in
      potentially accessible regions of their alpha1 alpha2 domains, they were
      recognized by diverse human intestinal epithelial gamma delta T cells that are
      restricted by MICA and MICB. Thus, MIC molecules represent a family of MHC
      proteins that are structurally diverse yet appear to be functionally conserved.
      The promiscuous mode of gamma delta T cell recognition of these antigens may be
      explained by their sharing of a single conserved interaction site.

PMID- 9770517
TI  - Gene therapy in allergic encephalomyelitis using myelin basic protein-specific T
      cells engineered to express latent transforming growth factor-beta1.
AB  - A myelin basic protein (MBP)-specific BALB/c T helper 1 (Th1) clone was
      transduced with cDNA for murine latent transforming growth factor-beta1 (TGF
      beta1) by coculture with fibroblasts producing a genetically engineered
      retrovirus. When SJL x BALB/c F1 mice, immunized 12-15 days earlier with
      proteolipid protein in complete Freund's adjuvant, were injected with 3 x 10(6)
      cells from MBP-activated untransduced cloned Th1 cells, the severity of
      experimental allergic encephalomyelitis (EAE) was slightly increased. In
      contrast, MBP-activated (but not resting) latent TGF-beta1-transduced T cells
      significantly delayed and ameliorated EAE development. This protective effect was
      negated by simultaneously injected anti-TGF-beta1. The transduced cells secreted
      2-4 ng/ml of latent TGF-beta1 into their culture medium, whereas control cells
      secreted barely detectable amounts. mRNA profiles for tumor necrosis factor,
      lymphotoxin, and interferon-gamma were similar before and after transduction;
      interleukin-4 and -10 were absent. TGF-beta1-transduced and antigen-activated
      BALB/c Th1 clones, specific for hemocyanin or ovalbumin, did not ameliorate EAE.
      Spinal cords from mice, taken 12 days after receiving TGF-beta1-transduced,
      antigen-activated cells, contained detectable amounts of TGF-beta1 cDNA. We
      conclude that latent TGF-beta1-transduced, self-reactive T cell clones may be
      useful in the therapy of autoimmune diseases.

PMID- 9770518
TI  - Kinetics of T cell receptor beta, gamma, and delta rearrangements during adult
      thymic development: T cell receptor rearrangements are present in CD44(+)CD25(+)
      Pro-T thymocytes.
AB  - We performed a comprehensive analysis of T cell receptor (TCR) gamma
      rearrangements in T cell precursors of the mouse adult thymus. Using a sensitive
      quantitative PCR method, we show that TCRgamma rearrangements are present in
      CD44(+)CD25(+) Pro-T thymocytes much earlier than expected. TCRgamma
      rearrangements increase significantly from the Pro-T to the CD44(-)CD25(+) Pre-T
      cell transition, and follow different patterns depending on each Vgamma gene
      segment, suggesting that ordered waves of TCRgamma rearrangement exist in the
      adult mouse thymus as has been described in the fetal mouse thymus.
      Recombinations of TCRgamma genes occur concurrently with TCRdelta and D-Jbeta
      rearrangements, but before Vbeta gene assembly. Productive TCRgamma
      rearrangements do not increase significantly before the Pre-T cell stage and are
      depleted in CD4(+)CD8(+) double-positive cells from normal mice. In contrast,
      double-positive thymocytes from TCRdelta-/- mice display random proportions of
      TCRgamma rearranged alleles, supporting a role for functional TCRgamma/delta
      rearrangements in the gammadelta divergence process.

PMID- 9770519
TI  - Synthetic amino acid copolymers that bind to HLA-DR proteins and inhibit type II
      collagen-reactive T cell clones.
AB  - Copolymer 1 [poly(Y,E,A,K)] is a random synthetic amino acid copolymer of L
      tyrosine, L-glutamic acid, L-alanine, and L-lysine that is effective both in
      suppression of experimental allergic encephalomyelitis and in the treatment of
      relapsing forms of multiple sclerosis. Copolymer 1 binds promiscuously and very
      efficiently to purified HLA-DR molecules within the peptide-binding groove. In
      the present study, YEAK and YEAK-related copolymers and type II collagen (CII)
      peptide 261-273, a candidate autoantigen in rheumatoid arthritis (RA), competed
      for binding to RA-associated HLA-DR molecules encoded by DRB1*0101 and DRB1*0401.
      Moreover, these copolymers (particularly YEAK, YAK, and YEK) inhibited the
      response of DR1- and DR4-restricted T cell clones to the CII epitope 261-273 by
      >50%. This direct evidence both for competitive interactions of these copolymers
      and CII peptide with RA-associated HLA-DR molecules and for inhibition of CII
      specific T cell responses suggests that these compounds should be evaluated in
      animal models for rheumatoid arthritis.

PMID- 9770520
TI  - Charge-dependent translocation of Bordetella pertussis adenylate cyclase toxin
      into eukaryotic cells: implication for the in vivo delivery of CD8(+) T cell
      epitopes into antigen-presenting cells.
AB  - Bordetella pertussis secretes a calmodulin-activated adenylate cyclase toxin,
      CyaA, that is able to deliver its N-terminal catalytic domain (400-aa residues)
      into the cytosol of eukaryotic target cells, directly through the cytoplasmic
      membrane. We have previously shown that CyaA can be used as a vehicle to deliver
      T cell epitopes, inserted within the catalytic domain of the toxin, into antigen
      presenting cells and can trigger specific class I-restricted CD8(+) cytotoxic T
      cell responses in vivo. Here, we constructed a series of recombinant toxins
      harboring at the same insertion site various peptide sequences of 11-25 amino
      acids, corresponding to defined CD8(+) T cell epitopes and differing in the
      charge of the inserted sequence. We show that inserted peptide sequences
      containing net negative charges (-1 or -2) decreased or completely blocked
      (charge of -4) the internalization of the toxin into target cells in vitro and
      abolished the induction of cytotoxic T cell responses in vivo. The blocking of
      translocation due to the inserted acidic sequences can be relieved by appropriate
      mutations in the flanking region of CyaA that counterbalance the inserted
      charges. Our data indicate that (i) the electrostatic charge of the peptides
      inserted within the catalytic domain of CyaA is critical for its translocation
      into eukaryotic cells and (ii) the delivery of T cell epitopes into the cytosol
      of antigen-presenting cells by recombinant CyaA toxins is essential for the in
      vivo stimulation of specific cytotoxic T cells. These findings will help to
      engineer improved recombinant CyaA vectors able to stimulate more efficiently
      cellular immunity.

PMID- 9770521
TI  - Major histocompatibility complex class I-restricted T cells are required for all
      but the end stages of diabetes development in nonobese diabetic mice and use a
      prevalent T cell receptor alpha chain gene rearrangement.
AB  - Nonobese diabetic (NOD) mice develop insulin-dependent diabetes mellitus due to
      autoimmune T lymphocyte-mediated destruction of pancreatic beta cells. Although
      both major histocompatibility complex class I-restricted CD8(+) and class II
      restricted CD4(+) T cell subsets are required, the specific role each subset
      plays in the pathogenic process is still unclear. Here we show that class I
      dependent T cells are required for all but the terminal stages of autoimmune
      diabetes development. To characterize the diabetogenic CD8(+) T cells
      responsible, we isolated and propagated in vitro CD8(+) T cells from the earliest
      insulitic lesions of NOD mice. They were cytotoxic to NOD islet cells, restricted
      to H-2Kd, and showed a diverse T cell receptor beta chain repertoire. In
      contrast, their alpha chain repertoire was more restricted, with a recurrent
      amino acid sequence motif in the complementarity-determining region 3 loop and a
      prevalence of Valpha17 family members frequently joined to the Jalpha42 gene
      segment. These results suggest that a number of the CD8(+) T cells participating
      in the initial phase of autoimmune beta cell destruction recognize a common
      structural component of Kd/peptide complexes on pancreatic beta cells, possibly a
      single peptide.

PMID- 9770522
TI  - Neuropeptides, by direct interaction with T cells, induce cytokine secretion and
      break the commitment to a distinct T helper phenotype.
AB  - Searching for nervous system candidates that could directly induce T cell
      cytokine secretion, I tested four neuropeptides (NPs): somatostatin, calcitonin
      gene-related peptide, neuropeptide Y, and substance P. Comparing neuropeptide
      driven versus classical antigen-driven cytokine secretion from T helper cells
      Th0, Th1, and Th2 autoimmune-related T cell populations, I show that the tested
      NPs, in the absence of any additional factors, directly induce a marked secretion
      of cytokines [interleukin 2 (IL-2), interferon-gamma, IL-4, and IL-10) from T
      cells. Furthermore, NPs drive distinct Th1 and Th2 populations to a "forbidden"
      cytokine secretion: secretion of Th2 cytokines from a Th1 T cell line and vice
      versa. Such a phenomenon cannot be induced by classical antigenic stimulation. My
      study suggests that the nervous system, through NPs interacting with their
      specific T cell-expressed receptors, can lead to the secretion of both typical
      and atypical cytokines, to the breakdown of the commitment to a distinct Th
      phenotype, and a potentially altered function and destiny of T cells in vivo.

PMID- 9770523
TI  - Interleukin 18 stimulates HIV type 1 in monocytic cells.
AB  - The cytokine interleukin (IL) 18 (formerly interferon gamma-inducing factor)
      induces the T helper type 1 response. In the present studies, IL-18 increased HIV
      type 1 (HIV-1) production from 5- to 30-fold in the chronically infected U1
      monocytic cell line. Inhibition of tumor necrosis factor (TNF) activity by the
      addition of TNF-binding protein reduced IL-18-stimulated HIV-1 production by 48%.
      In the same cultures, IL-18-induced IL-8 was inhibited by 96%. Also, a
      neutralizing anti-IL-6 mAb reduced IL-18-induced HIV-1 by 63%. Stimulation of U1
      cells with IL-18 resulted in increased production of IL-6, and exogenous IL-6
      added to U1 cells increased HIV-1 production 4-fold over control. A specific
      inhibitor of the p38 mitogen-activated protein kinase reduced IL-18-induced HIV-1
      by 73%, and a 50% inhibition was observed at 0.05 microM. In the same cultures,
      IL-8 was inhibited by 87%. By gel-shift and supershift analyses, increased
      binding activity of the transcription factor NF-kappaB was measured in nuclear
      extracts from U1 cells 1 h after exposure to IL-18. These results demonstrate
      induction of HIV-1 by IL-18 in a monocyte target associated with an intermediate
      role for TNF and IL-6, activation of p38 mitogen-activated protein kinase, and
      nuclear translocation of NF-kappaB.

PMID- 9770525
TI  - Crystal structure of Taq DNA polymerase in complex with an inhibitory Fab: the
      Fab is directed against an intermediate in the helix-coil dynamics of the enzyme.
AB  - We report the crystal structure of Thermus aquaticus DNA polymerase I in complex
      with an inhibitory Fab, TP7, directed against the native enzyme. Some of the
      residues present in a helical conformation in the native enzyme have adopted a
      gamma turn conformation in the complex. Taken together, structural information
      that describes alteration of helical structure and solution studies that
      demonstrate the ability of TP7 to inhibit 100% of the polymerase activity of the
      enzyme suggest that the change in conformation is probably caused by trapping of
      an intermediate in the helix-coil dynamics of this helix by the Fab. Antibodies
      directed against modified helices in proteins have long been anticipated. The
      present structure provides direct crystallographic evidence. The Fab binds within
      the DNA binding cleft of the polymerase domain, interacting with several residues
      that are used by the enzyme in binding the primer:template complex. This result
      unequivocally corroborates inferences drawn from binding experiments and modeling
      calculations that the inhibitory activity of this Fab is directly attributable to
      its interference with DNA binding by the polymerase domain of the enzyme. The
      combination of interactions made by the Fab residues in both the polymerase and
      the vestigial editing nuclease domain of the enzyme reveal the structural basis
      of its preference for binding to DNA polymerases of the Thermus species. The
      orientation of the structure-specific nuclease domain with respect to the
      polymerase domain is significantly different from that seen in other structures
      of this polymerase. This reorientation does not appear to be antibody-induced and
      implies remarkably high relative mobility between these two domains.

PMID- 9770524
TI  - CXCR4 and CD4 mediate a rapid CD95-independent cell death in CD4(+) T cells.
AB  - AIDS is characterized by a progressive decrease of CD4(+) helper T lymphocytes.
      Destruction of these cells may involve programmed cell death, apoptosis. It has
      previously been reported that apoptosis can be induced even in noninfected cells
      by HIV-1 gp120 and anti-gp120 antibodies. HIV-1 gp120 binds to T cells via CD4
      and the chemokine coreceptor CXCR4 (fusin/LESTR). Therefore, we investigated
      whether CD4 and CXCR4 mediate gp120-induced apoptosis. We used human peripheral
      blood lymphocytes, malignant T cells, and CD4/CXCR4 transfectants, and found cell
      death induced by both cell surface receptors, CD4 and CXCR4. The induced cell
      death was rapid, independent of known caspases, and lacking oligonucleosomal DNA
      fragmentation. In addition, the death signals were not propagated via p56(lck)
      and Gialpha. However, the cells showed chromatin condensation, morphological
      shrinkage, membrane inversion, and reduced mitochondrial transmembrane potential
      indicative of apoptosis. Significantly, apoptosis was exclusively observed in
      CD4(+) but not in CD8(+) T cells, and apoptosis triggered via CXCR4 was inhibited
      by stromal cell-derived factor-1, the natural CXCR4 ligand. Thus, this mechanism
      of apoptosis might contribute to T cell depletion in AIDS and might have major
      implications for therapeutic intervention.

PMID- 9770526
TI  - Patterns of HIV-1 evolution in individuals with differing rates of CD4 T cell
      decline.
AB  - Evolution of HIV-1 env sequences was studied in 15 seroconverting injection drug
      users selected for differences in the extent of CD4 T cell decline. The rates of
      increase of either sequence diversity at a given visit or divergence from the
      first seropositive visit were both higher in progressors than in nonprogressors.
      Viral evolution in individuals with rapid or moderate disease progression showed
      selection favoring nonsynonymous mutations, while nonprogressors with low viral
      loads selected against the nonsynonymous mutations that might have resulted in
      viruses with higher levels of replication. For 10 of the 15 subjects no single
      variant predominated over time. Evolution away from a dominant variant was
      followed frequently at a later time point by return to dominance of strains
      closely related to that variant. The observed evolutionary pattern is consistent
      with either selection against only the predominant virus or independent evolution
      occurring in different environments within the host. Differences in the level to
      which CD4 T cells fall in a given time period reflect not only quantitative
      differences in accumulation of mutations, but differences in the types of
      mutations that provide the best adaptation to the host environment.

PMID- 9770527
TI  - Mycobacterium avium complex augments macrophage HIV-1 production and increases
      CCR5 expression.
AB  - Infection with HIV-1 results in pronounced immune suppression and susceptibility
      to opportunistic infections (OI). Reciprocally, OI augment HIV-1 replication. As
      we have shown for Mycobacterium avium complex (MAC) and Pneumocystis carinii,
      macrophages infected with opportunistic pathogens and within lymphoid tissues
      containing OI, exhibit striking levels of viral replication. To explore potential
      underlying mechanisms for increased HIV-1 replication associated with
      coinfection, blood monocytes were exposed to MAC antigens (MAg) or viable MAC and
      their levels of tumor necrosis factor alpha (TNFalpha) and HIV-1 coreceptors
      monitored. MAC enhanced TNFalpha production in vitro, consistent with its
      expression in coinfected lymph nodes. Using a polyclonal antibody to the CCR5
      coreceptor that mediates viral entry of macrophage tropic HIV-1, a subset of
      unstimulated monocytes was shown to be CCR5-positive by fluorescence-activated
      cell sorter analysis. After stimulation with MAg or infection with MAC, CCR5
      expression was increased at both the mRNA level and on the cell surface. Up
      regulation of CCR5 by MAC was not paralleled by an increase in the T cell tropic
      coreceptor, CXCR4. Increases in NF-kappaB, TNFalpha, and CCR5 were consistent
      with the enhanced production of HIV-1 in MAg-treated adherent macrophage cultures
      as measured by HIV-1 p24 levels. Increased CCR5 was also detected in coinfected
      lymph nodes as compared with tissues with only HIV-1. The increased production of
      TNFalpha, together with elevated expression of CCR5, provide potential mechanisms
      for enhanced infection and replication of HIV-1 by macrophages in OI-infected
      cells and tissues. Consequently, treating OI may inhibit not only the OI-induced
      pathology, but also limit the viral burden.

PMID- 9770528
TI  - Doxycycline control of prion protein transgene expression modulates prion disease
      in mice.
AB  - Conversion of the cellular prion protein (PrPC) into the pathogenic isoform
      (PrPSc) is the fundamental event underlying transmission and pathogenesis of
      prion diseases. To control the expression of PrPC in transgenic (Tg) mice, we
      used a tetracycline controlled transactivator (tTA) driven by the PrP gene
      control elements and a tTA-responsive promoter linked to a PrP gene [Gossen, M.
      and Bujard, H. (1992) Proc. Natl. Acad. Sci. USA 89, 5547-5551]. Adult Tg mice
      showed no deleterious effects upon repression of PrPC expression (>90%) by oral
      doxycycline, but the mice developed progressive ataxia at approximately 50 days
      after inoculation with prions unless maintained on doxycycline. Although Tg mice
      on doxycycline accumulated low levels of PrPSc, they showed no neurologic
      dysfunction, indicating that low levels of PrPSc can be tolerated. Use of the tTA
      system to control PrP expression allowed production of Tg mice with high levels
      of PrP that otherwise cause many embryonic and neonatal deaths. Measurement of
      PrPSc clearance in Tg mice should be possible, facilitating the development of
      pharmacotherapeutics.

PMID- 9770529
TI  - Overexpression of DNA polymerase beta in cell results in a mutator phenotype and
      a decreased sensitivity to anticancer drugs.
AB  - DNA polymerase beta (pol beta) is the most error prone of all known eukaryotic
      DNA polymerases tested in vitro. Here, we show that cells overexpressing pol beta
      cDNA have acquired a spontaneous mutator phenotype. By measuring the appearance
      of mutational events using three independent assays, we found that genetic
      instability increased in the cell lines that overexpressed pol beta. In addition,
      these cells displayed a decreased sensitivity to cancer chemotherapeutic,
      bifunctional, DNA-damaging agents such as cisplatin, melphalan, and
      mechlorethamine, resulting in enhanced mutagenesis compared with control cells.
      By using cell-free extracts and modified DNA substrates, we present data in
      support of error-prone translesion replication as one of the key determinants of
      tolerance phenotype. These results have implications for the potential role of
      pol beta overexpression in cancer predisposition and tumor progression during
      chemotherapy.

PMID- 9770530
TI  - Fibrinogen deficiency reduces vascular accumulation of apolipoprotein(a) and
      development of atherosclerosis in apolipoprotein(a) transgenic mice.
AB  - To test directly whether fibrin(ogen) is a key binding site for apolipoprotein(a)
      [apo(a)] in vessel walls, apo(a) transgenic mice and fibrinogen knockout mice
      were crossed to generate fibrin(ogen)-deficient apo(a) transgenic mice and
      control mice. In the vessel wall of apo(a) transgenic mice, fibrin(ogen)
      deposition was found to be essentially colocalized with focal apo(a) deposition
      and fatty-streak type atherosclerotic lesions. Fibrinogen deficiency in apo(a)
      transgenic mice decreased the average accumulation of apo(a) in vessel walls by
      78% and the average lesion (fatty streak type) development by 81%. Fibrinogen
      deficiency in wild-type mice did not significantly reduce lesion development. Our
      results suggest that fibrin(ogen) provides one of the major sites to which apo(a)
      binds to the vessel wall and participates in the generation of atherosclerosis.

PMID- 9770531
TI  - Down-regulation of transmembrane carbonic anhydrases in renal cell carcinoma cell
      lines by wild-type von Hippel-Lindau transgenes.
AB  - To discover genes involved in von Hippel-Lindau (VHL)-mediated carcinogenesis, we
      used renal cell carcinoma cell lines stably transfected with wild-type VHL
      expressing transgenes. Large-scale RNA differential display technology applied to
      these cell lines identified several differentially expressed genes, including an
      alpha carbonic anhydrase gene, termed CA12. The deduced protein sequence was
      classified as a one-pass transmembrane CA possessing an apparently intact
      catalytic domain in the extracellular CA module. Reintroduced wild-type VHL
      strongly inhibited the overexpression of the CA12 gene in the parental renal cell
      carcinoma cell lines. Similar results were obtained with CA9, encoding another
      transmembrane CA with an intact catalytic domain. Although both domains of the
      VHL protein contribute to regulation of CA12 expression, the elongin binding
      domain alone could effectively regulate CA9 expression. We mapped CA12 and CA9
      loci to chromosome bands 15q22 and 17q21.2 respectively, regions prone to
      amplification in some human cancers. Additional experiments are needed to define
      the role of CA IX and CA XII enzymes in the regulation of pH in the extracellular
      microenvironment and its potential impact on cancer cell growth.

PMID- 9770532
TI  - Rates of ubiquitin conjugation increase when muscles atrophy, largely through
      activation of the N-end rule pathway.
AB  - The rapid loss of muscle mass that accompanies many disease states, such as
      cancer or sepsis, is primarily a result of increased protein breakdown in muscle,
      and several observations have suggested an activation of the ubiquitin-proteasome
      system. Accordingly, in extracts of atrophying muscles from tumor-bearing or
      septic rats, rates of 125I-ubiquitin conjugation to endogenous proteins were
      found to be higher than in control extracts. On the other hand, in extracts of
      muscles from hypothyroid rats, where overall proteolysis is reduced below normal,
      the conjugation of 125I-ubiquitin to soluble proteins decreased by 50%, and
      treatment with triiodothyronine (T3) restored ubiquitination to control levels.
      Surprisingly, the N-end rule pathway, which selectively degrades proteins with
      basic or large hydrophobic N-terminal residues, was found to be responsible for
      most of these changes in ubiquitin conjugation. Competitive inhibitors of this
      pathway that specifically block the ubiquitin ligase, E3alpha, suppressed most of
      the increased ubiquitin conjugation in the muscle extracts from tumor-bearing and
      septic rats. These inhibitors also suppressed ubiquitination in normal extracts
      toward levels in hypothyroid extracts, which showed little E3alpha-dependent
      ubiquitination. Thus, the inhibitors eliminated most of the differences in
      ubiquitination under these different pathological conditions. Moreover, 125I
      lysozyme, a model N-end rule substrate, was ubiquitinated more rapidly in
      extracts from tumor-bearing and septic rats, and more slowly in those from
      hypothyroid rats, than in controls. Thus, the rate of ubiquitin conjugation
      increases in atrophying muscles, and these hormone- and cytokine-dependent
      responses are in large part due to activation of the N-end rule pathway.

PMID- 9770533
TI  - Abrogation of the G2 cell cycle checkpoint associated with overexpression of
      HSIX1: a possible mechanism of breast carcinogenesis.
AB  - While conducting a search for cell cycle-regulated genes in human mammary
      carcinoma cells, we identified HSIX1, a recently discovered member of a new
      homeobox gene subfamily. HSIX1 expression was absent at the onset of and
      increased toward the end of S phase. Since its expression pattern is suggestive
      of a role after S phase, we investigated the effect of HSIX1 in the G2 cell cycle
      checkpoint. Overexpression of HSIX1 in MCF7 cells abrogated the G2 cell cycle
      checkpoint in response to x-ray irradiation. HSIX1 expression was absent or very
      low in normal mammary tissue, but was high in 44% of primary breast cancers and
      90% of metastatic lesions. In addition, HSIX1 was expressed in a variety of
      cancer cell lines, suggesting an important function in multiple tumor types.
      These data support the role for homeobox genes in tumorigenesis/tumor
      progression, possibly through a cell cycle function.

PMID- 9770534
TI  - Deficient DNA-ligase activity in the metabolic disease tyrosinemia type I.
AB  - Hereditary tyrosinemia type I (HT1) is an autosomal recessive inborn error of
      metabolism caused by the deficiency of fumarylacetoacetate hydrolase, the last
      enzyme in the tyrosine catabolism pathway. This defect results in accumulation of
      succinylacetone (SA) that reacts with amino acids and proteins to form stable
      adducts via Schiff base formation, lysine being the most reactive amino acid. HT1
      patients surviving beyond infancy are at considerable risk for the development of
      hepatocellular carcinoma, and a high level of chromosomal breakage is observed in
      HT1 cells, suggesting a defect in the processing of DNA. In this paper we show
      that the overall DNA-ligase activity is low in HT1 cells (about 20% of the normal
      value) and that Okazaki fragments are rejoined at a reduced rate compared with
      normal fibroblasts. No mutation was found by sequencing the ligase I cDNA from
      HT1 cells, and the level of expression of the ligase I mRNA was similar in normal
      and HT1 fibroblasts, suggesting the presence of a ligase inhibitor. SA was shown
      to inhibit in vitro the overall DNA-ligase activity present in normal cell
      extracts. The activity of purified T4 DNA-ligase, whose active site is also a
      lysine residue, was inhibited by SA in a dose-dependent manner. These results
      suggest that accumulation of SA reduces the overall ligase activity in HT1 cells
      and indicate that metabolism errors may play a role in regulating enzymatic
      activities involved in DNA replication and repair.

PMID- 9770535
TI  - Free recombination within Helicobacter pylori.
AB  - Sequences of three gene fragments (flaA, flaB, and vacA) from Helicobacter pylori
      strains isolated from patients in Germany, Canada, and South Africa were analyzed
      for diversity and for linkage equilibrium by using the Homoplasy Test and
      compatibility matrices. Horizontal genetic exchange in H. pylori is so frequent
      that different loci and polymorphisms within each locus are all at linkage
      equilibrium. These results indicate that H. pylori is panmictic. Comparisons with
      sequences from Escherichia coli, Neisseria meningitidis, and Drosophila
      melanogaster showed that recombination in H. pylori was much more frequent than
      in other species. In contrast, when multiple family members infected with H.
      pylori were investigated, some strains were indistinguishable at all three loci.
      Thus, H. pylori is clonal over short time periods after natural transmission.

PMID- 9770536
TI  - Molecular characterization of the mycobacterial heparin-binding hemagglutinin, a
      mycobacterial adhesin.
AB  - Although it generally is accepted that the interaction of Mycobacterium
      tuberculosis with alveolar macrophages is a key step in the pathogenesis of
      tuberculosis, interactions with other cell types, especially epithelial cells,
      also may be important. In this study we describe the molecular characterization
      of a mycobacterial heparin-binding hemagglutinin (HBHA), a protein that functions
      as an adhesin for epithelial cells. The structural gene was cloned from M.
      tuberculosis and bacillus Calmette-Guerin, and the sequence was found to be
      identical between the two species. The calculated Mr was smaller than the
      observed Mr when analyzed by SDS/PAGE. This difference can be attributed to the
      Lys/Pro-rich repeats that occur at the C-terminal end of the protein and to a
      putative carbohydrate moiety. Glycosylation of HBHA appears to protect the
      protein from proteolytic degradation, which results in the removal of the C
      terminal Lys/Pro-rich region responsible for binding of HBHA to sulfated
      carbohydrates. Evidence suggests that glycosylation is also important for HBHA
      mediated hemagglutination and for certain immunologic properties of the protein.
      Finally, the absence of a signal peptide in the coding region of HBHA raises the
      possibility that this protein is not secreted via the general secretion pathway.

PMID- 9770537
TI  - Sequence motifs in adenoviral DNA block immune activation by stimulatory CpG
      motifs.
AB  - Unmethylated CpG dinucleotides in particular base contexts (CpG-S motifs) are
      relatively common in bacterial DNA but are rare in vertebrate DNA. B cells and
      monocytes have the ability to detect such CpG-S motifs that trigger innate immune
      defenses with production of Th1-like cytokines. Despite comparable levels of
      unmethylated CpG dinucleotides, DNA from serotype 12 adenovirus is immune
      stimulatory, but serotype 2 is nonstimulatory and can even inhibit activation by
      bacterial DNA. In type 12 genomes, the distribution of CpG-flanking bases is
      similar to that predicted by chance. However, in type 2 adenoviral DNA the immune
      stimulatory CpG-S motifs are outnumbered by a 15- to 30-fold excess of CpG
      dinucleotides in clusters of direct repeats or with a C on the 5' side or a G on
      the 3' side. Synthetic oligodeoxynucleotides containing these putative
      neutralizing (CpG-N) motifs block immune activation by CpG-S motifs in vitro and
      in vivo. Eliminating 52 of the 134 CpG-N motifs present in a DNA vaccine markedly
      enhanced its Th1-like function in vivo, which was increased further by the
      addition of CpG-S motifs. Thus, depending on the CpG motif, prokaryotic DNA can
      be either immune-stimulatory or neutralizing. These results have important
      implications for understanding microbial pathogenesis and molecular evolution and
      for the clinical development of DNA vaccines and gene therapy vectors.

PMID- 9770538
TI  - Detection of 400-year-old Yersinia pestis DNA in human dental pulp: an approach
      to the diagnosis of ancient septicemia.
AB  - Ancient septicemic plague epidemics were reported to have killed millions of
      people for 2 millenniums. However, confident diagnosis of ancient septicemia
      solely on the basis of historical clinical observations is not possible. The lack
      of suitable infected material has prevented direct demonstration of ancient
      septicemia; thus, the history of most infections such as plague remains
      hypothetical. The durability of dental pulp, together with its natural sterility,
      makes it a suitable material on which to base such research. We hypothesized that
      it would be a lasting refuge for Yersinia pestis, the plague agent. DNA extracts
      were made from the dental pulp of 12 unerupted teeth extracted from skeletons
      excavated from 16th and 18th century French graves of persons thought to have
      died of plague ("plague teeth") and from 7 ancient negative control teeth. PCRs
      incorporating ancient DNA extracts and primers specific for the human beta-globin
      gene demonstrated the absence of inhibitors in these preparations. The
      incorporation of primers specific for Y. pestis rpoB (the RNA polymerase beta
      subunit-encoding gene) and the recognized virulence-associated pla (the
      plasminogen activator-encoding gene) repeatedly yielded products that had a
      nucleotide sequence indistinguishable from that of modern day isolates of the
      bacterium. The specific pla sequence was obtained from 6 of 12 plague skeleton
      teeth but 0 of 7 negative controls (P < 0.034, Fisher exact test). A nucleic acid
      based confirmation of ancient plague was achieved for historically identified
      victims, and we have confirmed the presence of the disease at the end of 16th
      century in France. Dental pulp is an attractive target in the quest to determine
      the etiology of septicemic illnesses detected in ancient corpses. Molecular
      techniques could be applied to this material to resolve historical outbreaks.

PMID- 9770539
TI  - Human milk lactoferrin inactivates two putative colonization factors expressed by
      Haemophilus influenzae.
AB  - Haemophilus influenzae is a major cause of otitis media and other respiratory
      tract disease in children. The pathogenesis of disease begins with colonization
      of the upper respiratory mucosa, a process that involves evasion of local immune
      mechanisms and adherence to epithelial cells. Several studies have demonstrated
      that human milk is protective against H. influenzae colonization and disease. In
      the present study, we examined the effect of human milk on the H. influenzae IgA1
      protease and Hap adhesin, two autotransported proteins that are presumed to
      facilitate colonization. Our results demonstrated that human milk lactoferrin
      efficiently extracted the IgA1 protease preprotein from the bacterial outer
      membrane. In addition, lactoferrin specifically degraded the Hap adhesin and
      abolished Hap-mediated adherence. Extraction of IgA1 protease and degradation of
      Hap were localized to the N-lobe of the bilobed lactoferrin molecule and were
      inhibited by serine protease inhibitors, suggesting that the lactoferrin N-lobe
      may contain serine protease activity. Additional experiments revealed no effect
      of lactoferrin on the H. influenzae P2, P5, and P6 outer-membrane proteins, which
      are distinguished from IgA1 protease and Hap by the lack of an N-terminal
      passenger domain or an extracellular linker region. These results suggest that
      human milk lactoferrin may attenuate the pathogenic potential of H. influenzae by
      selectively inactivating IgA1 protease and Hap, thereby interfering with
      colonization. Future studies should examine the therapeutic potential of
      lactoferrin, perhaps as a supplement in infant formulas.

PMID- 9770540
TI  - Echo-delay resolution in sonar images of the big brown bat, Eptesicus fuscus.
AB  - Echolocating big brown bats (Eptesicus fuscus) broadcast ultrasonic frequency
      modulated (FM) biosonar sounds (20-100 kHz frequencies; 10-50 microseconds
      periods) and perceive target range from echo delay. Knowing the acuity for delay
      resolution is essential to understand how bats process echoes because they
      perceive target shape and texture from the delay separation of multiple
      reflections. Bats can separately perceive the delays of two concurrent
      electronically generated echoes arriving as little as 2 microseconds apart, thus
      resolving reflecting points as close together as 0.3 mm in range (two-point
      threshold). This two-point resolution is roughly five times smaller than the
      shortest periods in the bat's sounds. Because the bat's broadcasts are 2,000
      4,500 microseconds long, the echoes themselves overlap and interfere with each
      other, to merge together into a single sound whose spectrum is shaped by their
      mutual interference depending on the size of the time separation. To separately
      perceive the delays of overlapping echoes, the bat has to recover information
      about their very small delay separation that was transferred into the spectrum
      when the two echoes interfered with each other, thus explicitly reconstructing
      the range profile of targets from the echo spectrum. However, the bat's 2
      microseconds resolution limit is so short that the available spectral cues are
      extremely limited. Resolution of delay seems overly sharp just for interception
      of flying insects, which suggests that the bat's biosonar images are of higher
      quality to suit a wider variety of orientation tasks, and that biosonar echo
      processing is correspondingly more sophisticated than has been suspected.

PMID- 9770541
TI  - Selective loss of dopaminergic nigro-striatal neurons in brains of Atm-deficient
      mice.
AB  - Ataxia-telangiectasia (AT) is a human disease caused by mutations in the ATM
      gene. The neural phenotype of AT includes progressive cerebellar
      neurodegeneration, which results in ataxia and eventual motor dysfunction.
      Surprisingly, mice in which the Atm gene has been inactivated lack distinct
      behavioral ataxia or pronounced cerebellar degeneration, the hallmarks of the
      human disease. To determine whether lack of the Atm protein can nonetheless lead
      to structural abnormalities in the brain, we compared brains from male Atm
      deficient mice with male, age-matched controls. Atm-deficient mice exhibited
      severe degeneration of tyrosine hydroxylase-positive, dopaminergic nigro-striatal
      neurons, and their terminals in the striatum. This cell loss was accompanied by a
      large reduction in immunoreactivity for the dopamine transporter in the striatum.
      A reduction in dopaminergic neurons also was evident in the ventral tegmental
      area. This effect was selective in that the noradrenergic nucleus locus coeruleus
      was normal in these mice. Behaviorally, Atm-deficient mice expressed locomotor
      abnormalities manifested as stride-length asymmetry, which could be corrected by
      peripheral application of the dopaminergic precursor L-dopa. In addition, these
      mice were hypersensitive to the dopamine releasing drug D-amphetamine. These
      results indicate that ATM deficiency can severely affect dopaminergic neurons in
      the central nervous system and suggest possible strategies for treating this
      aspect of the disease.

PMID- 9770542
TI  - Neural systems underlying learning and representation of global motion.
AB  - We demonstrate performance-related changes in cortical and cerebellar activity.
      The largest learning-dependent changes were observed in the anterior lateral
      cerebellum, where the extent and intensity of activation correlated inversely
      with psychophysical performance. After learning had occurred (a few minutes), the
      cerebellar activation almost disappeared; however, it was restored when the
      subjects were presented with a novel, untrained direction of motion for which
      psychophysical performance also reverted to chance level. Similar reductions in
      the extent and intensity of brain activations in relation to learning occurred in
      the superior colliculus, anterior cingulate, and parts of the extrastriate
      cortex. The motion direction-sensitive middle temporal visual complex was a
      notable exception, where there was an expansion of the cortical territory
      activated by the trained stimulus. Together, these results indicate that the
      learning and representation of visual motion discrimination are mediated by
      different, but probably interacting, neuronal subsystems.

PMID- 9770543
TI  - Experience-dependent corticofugal adjustment of midbrain frequency map in bat
      auditory system.
AB  - Recent studies of corticofugal modulation of auditory information processing
      indicate that cortical neurons mediate both a highly focused positive feedback to
      subcortical neurons "matched" in tuning to a particular acoustic parameter and a
      widespread lateral inhibition to "unmatched" subcortical neurons. This cortical
      function for the adjustment and improvement of subcortical information processing
      is called egocentric selection. Egocentric selection enhances the neural
      representation of frequently occurring signals in the central auditory system.
      For our present studies performed with the big brown bat (Eptesicus fuscus), we
      hypothesized that egocentric selection adjusts the frequency map of the inferior
      colliculus (IC) according to auditory experience based on associative learning.
      To test this hypothesis, we delivered acoustic stimuli paired with electric leg
      stimulation to the bat, because such paired stimuli allowed the animal to learn
      that the acoustic stimulus was behaviorally important and to make behavioral and
      neural adjustments based on the acquired importance of the acoustic stimulus. We
      found that acoustic stimulation alone evokes a change in the frequency map of the
      IC; that this change in the IC becomes greater when the acoustic stimulation is
      made behaviorally relevant by pairing it with electrical stimulation; that the
      collicular change is mediated by the corticofugal system; and that the IC itself
      can sustain the change evoked by the corticofugal system for some time. Our data
      support the hypothesis.

PMID- 9770544
TI  - Galanin regulates prolactin release and lactotroph proliferation.
AB  - The neuropeptide galanin is predominantly expressed by the lactotrophs (the
      prolactin secreting cell type) in the rodent anterior pituitary and in the median
      eminence and paraventricular nucleus of the hypothalamus. Prolactin and galanin
      colocalize in the same secretory granule, the expression of both proteins is
      extremely sensitive to the estrogen status of the animal. The administration of
      estradiol-17beta induces pituitary hyperplasia followed by adenoma formation and
      causes a 3,000-fold increase in the galanin mRNA content of the lactotroph. To
      further study the role of galanin in prolactin release and lactotroph growth we
      now report the generation of mice carrying a loss-of-function mutation of the
      endogenous galanin gene. There is no evidence of embryonic lethality and the
      mutant mice grow normally. The specific endocrine abnormalities identified to
      date, relate to the expression of prolactin. Pituitary prolactin message levels
      and protein content of adult female mutant mice are reduced by 30-40% compared
      with wild-type controls. Mutant females fail to lactate and pups die of
      starvation/dehydration unless fostered onto wild-type mothers. Prolactin
      secretion in mutant females is markedly reduced at 7 days postpartum compared
      with wild-type controls with an associated failure in mammary gland maturation.
      There is an almost complete abrogation of the proliferative response of the
      lactotroph to high doses of estrogen, with a failure to up-regulate prolactin
      release, STAT5 expression or to increase pituitary cell number. These data
      further support the hypothesis that galanin acts as a paracrine regulator of
      prolactin expression and as a growth factor to the lactotroph.

PMID- 9770545
TI  - Omega images at the active zone may be endocytotic rather than exocytotic:
      implications for the vesicle hypothesis of transmitter release.
AB  - A Ca2+-dependent synaptic vesicle-recycling pathway emanating from the plasma
      membrane adjacent to the dense body at the active zone has been demonstrated by
      blocking pinch-off of recycling membrane by using the Drosophila mutant, shibire.
      Exposure of wild-type Drosophila synapses to low Ca2+/high Mg2+ saline is shown
      here to block this active zone recycling pathway at the stage in which
      invaginations of the plasma membrane develop adjacent to the dense body. These
      observations, in combination with our previous demonstration that exposure to
      high Ca2+ causes "docked" vesicles to accumulate in the identical location where
      active zone endocytosis occurs, suggest the possibility that a vesicle-recycling
      pathway emanating from the active zone may exist that is stimulated by exposure
      to elevated Ca2+, thereby causing an increase in vesicle recycling, and is
      suppressed by exposure to low Ca2+ saline, thereby blocking newly forming
      vesicles at the invagination stage. The presence of a Ca2+-dependent endocytotic
      pathway at the active zone opens up the following possibilities: (i) electron
      microscopic omega-shaped images (and their equivalent, freeze fracture dimples)
      observed at the active zone adjacent to the dense body could represent
      endocytotic images (newly forming vesicles) rather than exocytotic images; (ii)
      vesicles observed attached to the plasma membrane adjacent to the dense body
      could represent newly formed vesicles rather than vesicles "docked" for release
      of transmitter.

PMID- 9770546
TI  - Memory-enhancing effects of secreted forms of the beta-amyloid precursor protein
      in normal and amnestic mice.
AB  - When administered intracerebroventricularly to mice performing various learning
      tasks involving either short-term or long-term memory, secreted forms of the beta
      amyloid precursor protein (APPs751 and APPs695) have potent memory-enhancing
      effects and block learning deficits induced by scopolamine. The memory-enhancing
      effects of APPs were observed over a wide range of extremely low doses (0.05
      5,000 pg intracerebroventricularly), blocked by anti-APPs antisera, and observed
      when APPs was administered either after the first training session in a visual
      discrimination or a lever-press learning task or before the acquisition trial in
      an object recognition task. APPs had no effect on motor performance or
      exploratory activity. APPs695 and APPs751 were equally effective in the object
      recognition task, suggesting that the memory-enhancing effect of APPs does not
      require the Kunitz protease inhibitor domain. These data suggest an important
      role for APPss on memory processes.

PMID- 9770547
TI  - Activation of nicotinic receptor-induced postsynaptic responses to luteinizing
      hormone-releasing hormone in bullfrog sympathetic ganglia via a Na+-dependent
      mechanism.
AB  - Nicotine at very low doses (5-30 nM) induced large amounts of luteinizing hormone
      releasing hormone (LHRH) release, which was monitored as slow membrane
      depolarizations in the ganglionic neurons of bullfrog sympathetic ganglia. A
      nicotinic antagonist, d-tubocurarine chloride, completely and reversibly blocked
      the nicotine-induced LHRH release, but it did not block the nerve-firing-evoked
      LHRH release. Thus, nicotine activated nicotinic acetylcholine receptors and
      produced LHRH release via a mechanism that is different from the mechanism for
      evoked release. Moreover, this release was not caused by Ca2+ influx through
      either the nicotinic receptors or the voltage-gated Ca2+ channels because the
      release was increased moderately when the extracellular solution was changed into
      a Ca2+-free solution that also contained Mg2+ (4 mM) and Cd2+ (200 microM). The
      release did not depend on Ca2+ release from the intraterminal Ca2+ stores either
      because fura-2 fluorimetry showed extremely low Ca2+ elevation (approximately 30
      nM) in response to nicotine (30 nM). Moreover, nicotine evoked LHRH release when
      [Ca2+] elevation in the terminals was prevented by loading the terminals with 1,2
      bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid and fura-2. Instead, the
      nicotine-induced release required extracellular Na+ because substitution of
      extracellular NaCl with N-methyl-D-glucamine chloride completely blocked the
      release. The Na+-dependent mechanism was not via Na+ influx through the voltage
      gated Na+ channels because the release was not affected by tetrodotoxin (1-50
      microM) plus Cd2+ (200 microM). Thus, nicotine at very low concentrations induced
      LHRH release via a Na+-dependent, Ca2+-independent mechanism.

PMID- 9770548
TI  - Neural basis of an inherited speech and language disorder.
AB  - Investigation of the three-generation KE family, half of whose members are
      affected by a pronounced verbal dyspraxia, has led to identification of their
      core deficit as one involving sequential articulation and orofacial praxis. A
      positron emission tomography activation study revealed functional abnormalities
      in both cortical and subcortical motor-related areas of the frontal lobe, while
      quantitative analyses of magnetic resonance imaging scans revealed structural
      abnormalities in several of these same areas, particularly the caudate nucleus,
      which was found to be abnormally small bilaterally. A recent linkage study
      [Fisher, S., Vargha-Khadem, F., Watkins, K. E., Monaco, A. P. & Pembry, M. E.
      (1998) Nat. Genet. 18, 168-170] localized the abnormal gene (SPCH1) to a 5. 6
      centiMorgan interval in the chromosomal band 7q31. The genetic mutation or
      deletion in this region has resulted in the abnormal development of several brain
      areas that appear to be critical for both orofacial movements and sequential
      articulation, leading to marked disruption of speech and expressive language.

PMID- 9770550
TI  - Mahogany (mg) stimulates feeding and increases basal metabolic rate independent
      of its suppression of agouti.
AB  - The mahogany (mg) locus originally was identified as a recessive suppressor of
      agouti, a locus encoding a skin peptide that modifies coat color by antagonizing
      the melanocyte-stimulating hormone receptor or MC1-R. Certain dominant alleles of
      agouti cause an obesity syndrome when ectopic expression of the peptide
      aberrantly antagonizes the MC4-R, a related melanocyte-stimulating hormone
      receptor expressed in hypothalamic circuitry and involved in the regulation of
      feeding behavior and metabolism. Recent work has demonstrated that mg, when
      homozygous, blocks not only the ability of agouti to induce a yellow coat color
      when expressed in the skin of the lethal yellow mouse (AY), but also the obesity
      resulting from ectopic expression of agouti in the brain. Detailed analysis of
      mg/mg AY/a animals, presented here, demonstrates that mg/mg blocks the obesity,
      hyperinsulinemia, and increased linear growth induced by ectopic expression of
      the agouti peptide. Remarkably, however, mg/mg did not reduce hyperphagia in the
      AY/a mouse. Furthermore, mg/mg induced hyperphagia and an increase in basal
      metabolic rate in the C57BL/6J mouse in the absence of AY. Consequently, although
      mahogany is broadly required for agouti peptide action, it also appears to be
      involved in the control of metabolic rate and feeding behavior independent of its
      suppression of agouti.

PMID- 9770549
TI  - 20-Hydroxyeicosatetraenoic acid mediates calcium/calmodulin-dependent protein
      kinase II-induced mitogen-activated protein kinase activation in vascular smooth
      muscle cells.
AB  - Norepinephrine (NE) and angiotensin II (Ang II), by promoting extracellular Ca2+
      influx, increase Ca2+/calmodulin-dependent kinase II (CaMKII) activity, leading
      to activation of mitogen-activated protein kinase (MAPK) and cytosolic
      phospholipase A2 (cPLA2), resulting in release of arachidonic acid (AA) for
      prostacyclin synthesis in rabbit vascular smooth muscle cells. However, the
      mechanism by which CaMKII activates MAPK is unclear. The present study was
      conducted to determine the contribution of AA and its metabolites as possible
      mediators of CaMKII-induced MAPK activation by NE, Ang II, and epidermal growth
      factor (EGF) in vascular smooth muscle cells. NE-, Ang II-, and EGF-stimulated
      MAPK and cPLA2 were reduced by inhibitors of cytochrome P450 (CYP450) and
      lipoxygenase but not by cyclooxygenase. NE-, Ang II-, and EGF-induced increases
      in Ras activity, measured by its translocation to plasma membrane, were abolished
      by CYP450, lipoxygenase, and farnesyltransferase inhibitors. An AA metabolite of
      CYP450, 20-hydroxyeicosatetraenoic acid (20-HETE), increased the activities of
      MAPK and cPLA2 and caused translocation of Ras. These data suggest that
      activation of MAPK by NE, Ang II, and EGF is mediated by a signaling mechanism
      involving 20-HETE, which is generated by stimulation of cPLA2 by CaMKII.
      Activation of Ras/MAPK by 20-HETE amplifies cPLA2 activity and releases
      additional AA by a positive feedback mechanism. This mechanism of Ras/MAPK
      activation by 20-HETE may play a central role in the regulation of other cellular
      signaling molecules involved in cell proliferation and growth.

PMID- 9770551
TI  - Inactivation of the mitogen-activated protein kinase Mps1 from the rice blast
      fungus prevents penetration of host cells but allows activation of plant defense
      responses.
AB  - The rice blast fungus, Magnaporthe grisea, generates enormous turgor pressure
      within a specialized cell called the appressorium to breach the surface of host
      plant cells. Here, we show that a mitogen-activated protein kinase, Mps1, is
      essential for appressorium penetration. Mps1 is 85% similar to yeast Slt2 mitogen
      activated protein kinase and can rescue the thermosensitive growth of slt2 null
      mutants. The mps1-1Delta mutants of M. grisea have some phenotypes in common with
      slt2 mutants of yeast, including sensitivity to cell-wall-digesting enzymes, but
      display additional phenotypes, including reduced sporulation and fertility.
      Interestingly, mps1-1Delta mutants are completely nonpathogenic because of the
      inability of appressoria to penetrate plant cell surfaces, suggesting that
      penetration requires remodeling of the appressorium wall through an Mps1
      dependent signaling pathway. Although mps1-1Delta mutants are unable to cause
      disease, they are able to trigger early plant-cell defense responses, including
      the accumulation of autofluorescent compounds and the rearrangement of the actin
      cytoskeleton. We conclude that MPS1 is essential for pathogen penetration;
      however, penetration is not required for induction of some plant defense
      responses.

PMID- 9770553
TI  - Ethylene-mediated phenotypic plasticity in root nodule development on Sesbania
      rostrata.
AB  - Leguminous plants in symbiosis with rhizobia form either indeterminate nodules
      with a persistent meristem or determinate nodules with a transient meristematic
      region. Sesbania rostrata was thought to possess determinate stem and root
      nodules. However, the nature of nodule development is hybrid, and the early
      stages resemble those of indeterminate nodules. Here we show that, depending on
      the environmental conditions, mature root nodules can be of the indeterminate
      type. In situ hybridizations with molecular markers for plant cell division, as
      well as the patterns of bacterial nod and nif gene expression, confirmed the
      indeterminate nature of 30-day-old functional root nodules. Experimental data
      provide evidence that the switch in nodule type is mediated by the plant hormone
      ethylene.

PMID- 9770552
TI  - Chlorophyll a oxygenase (CAO) is involved in chlorophyll b formation from
      chlorophyll a.
AB  - Chlorophyll b is an ubiquitous accessory pigment in land plants, green algae, and
      prochlorophytes. Its biosynthesis plays a key role in the adaptation to various
      light environments. We isolated six chlorophyll b-less mutants by insertional
      mutagenesis by using the nitrate reductase or argininosuccinate lyase genes as
      tags and examined the rearrangement of mutant genomes. We found that an
      overlapping region of a nuclear genome was deleted in all mutants and that this
      encodes a protein whose sequence is similar to those of methyl monooxygenases.
      This coding sequence also contains putative binding domains for a [2Fe-2S] Rieske
      center and for a mononuclear iron. The results demonstrate that a chlorophyll a
      oxygenase is involved in chlorophyll b formation. The reaction mechanism of
      chlorophyll b formation is discussed.

PMID- 9770554
TI  - A perceptual memory for low-contrast visual signals.
AB  - Detection of a visual signal can be facilitated by simultaneous presentation of a
      similar subthreshold signal. Here we show that the facilitatory effect of a
      subthreshold signal can persist for more than 16 s. Presenting a near-threshold
      Gabor signal (prime) produced a phase-independent increase in contrast
      sensitivity (40%) to similar successive signals (target) for a period of up to 16
      s. This effect was obtained only when both prime and target were presented to the
      same eye. We further show that the memory trace is inactivated by presenting high
      contrast signals before the target. These results suggest that activated neurons
      in the primary visual cortex retain a near-threshold memory trace that persists
      until reactivated.

PMID- 9770555
TI  - Incidence of dilated cardiomyopathy and detection of HIV in myocardial cells of
      HIV-positive patients. Gruppo Italiano per lo Studio Cardiologico dei Pazienti
      Affetti da AIDS.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) infection is increasingly
      recognized as an important cause of dilated cardiomyopathy. However, the
      pathogenesis of the heart-muscle disease in the acquired immunodeficiency
      syndrome is unclear. METHODS: We performed a prospective, long-term clinical and
      echocardiographic follow-up study of 952 asymptomatic HIV-positive patients to
      assess the incidence of dilated cardiomyopathy and to analyze the clinical
      variables associated with the development of cardiomyopathy. All patients with an
      echocardiographic diagnosis of dilated cardiomyopathy underwent endomyocardial
      biopsy for histologic, immunohistologic, and virologic assessment. RESULTS:
      During a mean (+/-SD) follow-up period of 60+/-5.3 months, an echocardiographic
      diagnosis of dilated cardiomyopathy was made in 76 patients (8 percent), with a
      mean annual incidence rate of 15.9 cases per 1000 patients. The incidence of
      dilated cardiomyopathy was higher in patients with a CD4 count of less than 400
      cells per cubic millimeter (as compared with a CD4 count of > or =400 cells per
      cubic millimeter) and in those who received therapy with zidovudine. A histologic
      diagnosis of myocarditis was made in 63 of the patients with dilated
      cardiomyopathy (83 percent). Inflammatory infiltrates were predominantly composed
      of CD3 and CD8 lymphocytes, with staining for major histocompatibility complex
      class I antigens in 71 percent of the patients. In the myocytes of 58 patients,
      HIV nucleic acid sequences were detected by in situ hybridization, and active
      myocarditis was documented in 36 of the 58. Among these 36 patients, 6 were also
      infected with coxsackievirus group B (17 percent), 2 with cytomegalovirus (6
      percent), and 1 with Epstein-Barr virus (3 percent). CONCLUSIONS: Dilated
      cardiomyopathy may be related either to a direct action of HIV on the myocardial
      tissue or to an autoimmune process induced by HIV, possibly in association with
      other cardiotropic viruses.

PMID- 9770556
TI  - Intolerance of cow's milk and chronic constipation in children.
AB  - BACKGROUND: Chronic diarrhea is the most common gastrointestinal symptom of
      intolerance of cow's milk among children. On the basis of a prior open study, we
      hypothesized that intolerance of cow's milk can also cause severe perianal
      lesions with pain on defecation and consequent constipation in young children.
      METHODS: We performed a double-blind, crossover study comparing cow's milk with
      soy milk in 65 children (age range, 11 to 72 months) with chronic constipation
      (defined as having one bowel movement every 3 to 15 days). All had been referred
      to a pediatric gastroenterology clinic and had previously been treated with
      laxatives without success; 49 had anal fissures and perianal erythema or edema.
      After 15 days of observation, the patients received cow's milk or soy milk for
      two weeks. After a one-week washout period, the feedings were reversed. A
      response was defined as eight or more bowel movements during a treatment period.
      RESULTS: Forty-four of the 65 children (68 percent) had a response while
      receiving soy milk. Anal fissures and pain with defecation resolved. None of the
      children who received cow's milk had a response. In all 44 children with a
      response, the response was confirmed with a double-blind challenge with cow's
      milk. Children with a response had a higher frequency of coexistent rhinitis,
      dermatitis, or bronchospasm than those with no response (11 of 44 children vs. 1
      of 21, P=0.05); they were also more likely to have anal fissures and erythema or
      edema at base line (40 of 44 vs. 9 of 21, P<0.001), evidence of inflammation of
      the rectal mucosa on biopsy (26 of 44 vs. 5 of 21, P=0.008), and signs of
      hypersensitivity, such as specific IgE antibodies to cow's-milk antigens (31 of
      44 vs. 4 of 21, P<0.001). CONCLUSIONS: In young children, chronic constipation
      can be a manifestation of intolerance of cow's milk.

PMID- 9770557
TI  - Electrical stimulation of the subthalamic nucleus in advanced Parkinson's
      disease.
AB  - BACKGROUND: In many patients with idiopathic Parkinson's disease, treatment with
      levodopa is complicated by fluctuations between an "off" period, when the
      medication is not working and the motor symptoms of parkinsonism are present, and
      an "on" period, when the medication is causing improved mobility, often
      accompanied by debilitating dyskinesias. In animal models of Parkinson's disease,
      there is overactivity in the subthalamic nucleus, and electrical stimulation of
      the subthalamic nucleus improves parkinsonism. We therefore sought to determine
      the efficacy and safety of electrical stimulation of the subthalamic nucleus in
      patients with Parkinson's disease. METHODS: We studied 24 patients with
      idiopathic Parkinson's disease in whom electrodes were implanted bilaterally in
      the subthalamic nucleus under stereotactic guidance with imaging and
      electrophysiologic testing of the location. Twenty were followed for at least 12
      months. Clinical evaluations included the Unified Parkinson's Disease Rating
      Scale, a dyskinesia scale, and timed tests conducted before and after surgery,
      when patients were off and on medications. RESULTS: After one year of electrical
      stimulation of the subthalamic nucleus, the patients' scores for activities of
      daily living and motor examination scores (Unified Parkinson's Disease Rating
      Scale parts II and III, respectively) off medication improved by 60 percent
      (P<0.001). The subscores improved for limb akinesia, rigidity, tremor, and gait.
      In the testing done on medication, the scores on part III improved by 10 percent
      (P<0.005). The mean dose of dopaminergic drugs was reduced by half. The cognitive
      performance scores remained unchanged, but one patient had paralysis and aphasia
      after an intracerebral hematoma during the implantation procedure. CONCLUSIONS:
      Electrical stimulation of the subthalamic nucleus is an effective treatment for
      advanced Parkinson's disease. The severity of symptoms off medication decreases,
      and the dose of levodopa can be reduced with consequent reduction in dyskinesias.

PMID- 9770558
TI  - Kashin-Beck osteoarthropathy in rural Tibet in relation to selenium and iodine
      status.
AB  - BACKGROUND AND METHODS: Kashin-Beck disease is a degenerative osteoarticular
      disorder that is endemic to certain areas of Tibet, where selenium deficiency is
      also endemic. Because selenium is involved in thyroid hormone metabolism, we
      studied the relation among the serum selenium concentration, thyroid function,
      and Kashin-Beck disease in 575 subjects 5 to 15 years of age in 12 villages
      around Lhasa, Tibet, including 1 control village in which no subject had Kashin
      Beck disease. Clinical, radiologic, and biochemical data were collected. RESULTS:
      Among the 575 subjects, 280 (49 percent) had Kashin-Beck disease, 267 (46
      percent) had goiter, and 7 (1 percent) had cretinism. Of the 557 subjects in whom
      urinary iodine was measured, 66 percent had a urinary iodine concentration of
      less than 2 microg per deciliter (157 nmol per liter; normal, 5 to 25 microg per
      deciliter [394 to 1968 nmol per liter]). The mean urinary iodine concentration
      was lower in subjects with Kashin-Beck disease than in control subjects (1.2 vs.
      1.8 microg per deciliter [94 vs. 142 nmol per liter], P<0.001) and hypothyroidism
      was more frequent (23 percent vs. 4 percent, P=0.01). Severe selenium deficiency
      was documented in all villages; 38 percent of subjects had serum concentrations
      of less than 5 ng per milliliter (64 nmol per liter; normal, 60 to 105 ng per
      milliliter [762 to 1334 nmol per liter]). When age and sex were controlled for in
      a multivariate analysis, low urinary iodine, high serum thyrotropin, and low
      serum thyroxine-binding globulin values were associated with an increased risk of
      Kashin-Beck disease, but a low serum selenium concentration was not. CONCLUSIONS:
      In areas where severe selenium deficiency is endemic, iodine deficiency is a risk
      factor for Kashin-Beck disease.

PMID- 9770559
TI  - Images in clinical medicine. Mediastinal goiter.

PMID- 9770560
TI  - Benefit of a favorable cardiovascular risk-factor profile in middle age with
      respect to Medicare costs.
AB  - BACKGROUND: People without major risk factors for cardiovascular disease in
      middle age live longer than those with unfavorable risk-factor profiles. It is
      not known whether such low-risk status also results in lower expenditures for
      medical care at older ages. We used data from the Chicago Heart Association
      Detection Project in Industry to assess the relation of a low risk of
      cardiovascular disease in middle age to Medicare expenditures later in life.
      METHODS: We studied 7039 men and 6757 women who were 40 to 64 years of age when
      surveyed between 1967 and 1973 and who survived to have at least two years of
      Medicare coverage in 1984 through 1994. Men and women classified as being at low
      risk for cardiovascular disease were those who had the following characteristics
      at the time they were initially surveyed: serum cholesterol level, <200 mg per
      deciliter (5.2 mmol per liter); blood pressure, < or =120/80 mm Hg; no current
      smoking; an absence of electrocardiographic abnormalities; no history of
      diabetes; and no history of myocardial infarction. We compared Medicare costs for
      the 279 men (4.0 percent) and 298 women (4.4 percent) who had this low-risk
      profile with those for the rest of the study group, who were not at low risk.
      Health Care Financing Administration charges for services to Medicare
      beneficiaries were used to estimate average annual health care costs (total
      costs, those for cardiovascular diseases, and those for cancer). RESULTS: Average
      annual health care charges were much lower for persons at low risk - the total
      charges for the men at low risk were less than two thirds of the charges for the
      men not at low risk ($1,615 less); for the women at low risk, the charges were
      less than one half of those for the women not at low risk ($1,885 less). Charges
      related to cardiovascular disease were lower for the low-risk groups of men and
      women than for those not at low risk (by $979 and $556, respectively), and
      charges related to cancer were also lower (by $134 and $189). CONCLUSIONS: People
      with favorable cardiovascular risk profiles in middle age had lower average
      annual Medicare charges in older age. Having optimal status with respect to major
      cardiovascular risk factors may result not only in greater longevity but also in
      lower health care costs.

PMID- 9770561
TI  - Parkinson's disease. Second of two parts.
AB  - At no time in the past have the basic and clinical sciences applied to
      Parkinson's disease been so active. Experimental therapies under study at present
      promise to improve on the limitations of existing treatments. Future progress in
      understanding the causation and pathogenesis of the disorder will permit the
      development of new treatments that will slow, halt, or even reverse the currently
      inexorable progressive course of Parkinson's disease.

PMID- 9770563
TI  - Dilated cardiomyopathy in HIV-infected patients.

PMID- 9770564
TI  - Constipation in children.

PMID- 9770565
TI  - Kashin-Beck disease--expanding the spectrum of iodine-deficiency disorders.

PMID- 9770566
TI  - Prevention and Medicare costs.

PMID- 9770568
TI  - A guide to pediatric cardiovascular physical examination 

PMID- 9770569
TI  - Effects of doxorubicin on diastolic function, contractile reserve, and
      ventricular-vascular coupling in piglets.
AB  - The use of doxorubicin as an anticancer drug is limited by its cardiac toxicity.
      To examine the adverse effects of doxorubicin on cardiac function and ventricular
      vascular coupling in piglets, eight piglets received five doses of intravenous
      doxorubicin, 1.5 mg/kg/dose, every 4-7 days starting at 3 weeks of age. A control
      group consisted of eight normal piglets. Using conductance and manometric
      catheters, indices of cardiac function, including end systolic elastance (Ees),
      preload-recruitable stroke work, dP/dtmax, tau, dP/dtmin, dV/dtmax, and end
      systolic stiffness, were calculated from volume and pressure measurements at rest
      and during infusion of isoproterenol. Ventricular-vascular coupling was examined
      by measuring arterial elastance (Ea) and Ea/Ees. Significant differences in
      relaxation were found between groups. Indices of diastolic stiffness and of
      contractile function were not different between groups. Baseline contractile
      efficiency was increased in the doxorubicin group. Ea and Ea/Ees were lower in
      the doxorubicin group. Ea/Ees was near 1 at baseline in the doxorubicin group,
      indicating that conditions were optimized for performance of external stroke
      work. Therefore, the reserve to increase external cardiac work was diminished.
      The finding of altered diastolic function suggests the importance of screening of
      diastolic indices to detect the earliest disturbances in cardiac function caused
      by doxorubicin.

PMID- 9770570
TI  - Historical vignette: coarctation of the aorta.

PMID- 9770567
TI  - Amiodarone used alone or in combination with propranolol: a very effective
      therapy for tachyarrhythmias in infants and children.
AB  - The aim of the study was to evaluate the efficacy of amiodarone used alone or in
      combination with propranolol in infants and children affected by life-threatening
      or drug-resistant tachyarrhythmias. The study included 27 children (median age 3
      months), affected by life-threatening and/or drug-resistant supraventricular or
      ventricular tachyarrhythmias. The loading dose of amiodarone was 10-20 mg/kg/day
      and the maintenance dose ranged between 3 and 20 mg/kg/day. When amiodarone was
      ineffective, propranolol was added at a dosage of 2-4 mg/kg/day. The study
      population was divided into two groups: group A was composed of patients <1 year
      and group B of patients >1 year. The effectiveness of the therapy was assessed by
      clinical evaluation, Holter monitoring, exercise testing, and, in patients with
      reentry tachycardias, electrophysiological testing. Amiodarone used alone was
      effective or partially effective in 4/14 (28%) patients in group A and in 11/13
      (85%) patients in group B (p < 0.006). Among amiodarone-resistant patients, the
      combined therapy with propranolol was effective in 8/10 patients in group A and
      2/2 patients in group B. Therefore, amiodarone used alone or in combination with
      propranolol was effective in 25/27 (93%) patients. During the follow-up (20.5 +/-
      13 months) there were no arrhythmic effects but side effects were noted in 5/27
      (18.5%) patients. Amiodarone seems to be an effective drug in the control of the
      life-threatening and/or drug-resistant supraventricular and ventricular
      tachyarrhythmias in children. The addition of propranolol can significantly
      enhance the success rate of this class III drug, especially in the treatment of
      reentry tachycardias due to accessory pathways.

PMID- 9770571
TI  - Innominate artery steal syndrome after stage I palliation for hypoplastic left
      heart syndrome.
AB  - Four neonates with hypoplastic left heart syndrome (HLHS) were found to have
      innominate artery steal syndrome (IASS) following stage I palliation with a
      modified Blalock-Taussig (B-T) shunt. All patients presented in the early
      postoperative period with a persistent supplemental oxygen requirement. Two
      dimensional echocardiography with Doppler flow analysis and cardiac
      catheterization with angiography demonstrated obstruction at the origin of the
      innominate artery. This obstruction was associated with intermittent retrograde
      flow through the right vertebral and common carotid arteries into the distal
      innominate artery and modified B-T shunt. An ascending neoaorta to right
      pulmonary artery shunt, with takedown of the B-T shunt, was performed in two of
      the patients. The other two patients were treated with percutaneous balloon
      dilatation of the obstructed area. Both procedures improved arterial blood oxygen
      saturations and eliminated the need for supplemental oxygen. In three of four
      patients, the left common carotid artery was found to be larger than the right.
      All four patients developed microcephaly, and one patient had encephalomalacia in
      the distribution of the right anterior and middle cerebral arteries. The
      development of IASS following stage I palliation for HLHS and the association of
      neurologic sequelae from this complication are discussed.

PMID- 9770572
TI  - Age-related variation in left ventricular myocardial contractile state expressed
      by the stress velocity relation.
AB  - The assessment of ventricular function plays an important role in the pre- and
      postoperative management of many congenital heart abnormalities. Normal ranges in
      left ventricular systolic function indices have been defined during childhood and
      age-related alterations in left ventricular myocardial contractile state have
      recently been reported. This study was carried out to investigate the
      developmental changes in left ventricular contractile state expressed by the
      endsystolic meridional stress (ESS)/rate-corrected velocity of circumferential
      fiber shortening (VCFc) relation, calculated by echo in normal children and young
      adults. We examined 146 healthy subjects (80 males and 66 females), mean age
      70.85 +/- 63.89 months (range 0.5-228) and body surface area (BSA) 0.807 +/- 0.
      47 (range 0.18-2.01) with no clinical and echocardiographic evidence of cardiac
      disease and with normal blood pressure. The subjects were divided into three
      groups according to age: <6 months (group 1, n = 32), 6-36 months (group 2, n =
      34), and >36 months (group 3, n = 80). Enddiastolic volume and mass (M) of the
      left ventricle were measured by M-mode Echo. ESS was considered as an index of
      afterload and the VCFc as an index of systolic ventricular function. The left
      ventricular ejection time used for the calculation of VCFc was measured from
      aortic flow obtained by PW-Doppler. The ESS/VCFc relation was used to assess left
      ventricular contractility. Systolic blood pressure, volume, and mass of the left
      ventricle increase with age. The gradual increase in pressure despite a stable
      mass/volume ratio [M/V = 0.900 + (0.0007 x age); r = 0.27, p < 0.005] resulted in
      a substantial increase of afterload [ESS = 29.78 + (0.116 x age); r = 0.58, p <
      0.0001]. VCFc showed an inverse hyperbolic regression with afterload [VCFc = 1.01
      + (7.598/ESS); r = 0.59, p < 0.0001]. The regression lines (best linear fit)
      between VCFc and ESS are significantly different in the three groups. The Y
      intercept was higher and the slope steeper in group 1 [VCFc = 1.74 - (0.017 x
      ESS); r = 0.65, p < 0.0005] vs group 2 [VCFc = 1.54 - (0.008 x ESS); r = 0.58, p
      < 0.001] and group 3 [VCFc = 1.52 - (0.007 x ESS); r = 0.57, p < 0.0001]. These
      data indicate that, in children, the volume and mass of the left ventricle
      increase, whereas the M/V ratio remains relatively constant; the progressive
      increase in arterial blood pressure explains the increase of afterload. The VCFc
      is higher in the first few years of life compared to that seen in older children
      due to reduced afterload and increased contractile state. Left ventricular
      contractility, expressed as ESS/VCFc relation, is thus inversely proportional to
      age. In the first months of life the left ventricular myocardium exhibits a
      higher basal contractile state and a greater sensitivity to changes in afterload.
      For obtaining an accurate assessment of left ventricular function, the ESS/VCFc
      relation in different age groups should be measured.

PMID- 9770573
TI  - Rapamycin (sirolimus) inhibits heart cell growth in vitro.
AB  - The success of infant and neonatal heart transplantation has increased
      dramatically since the mid-1980s. This success is due both to improved medical
      and surgical techniques and better pharmacological management of rejection
      episodes. We report here the results of in vitro studies designed to investigate
      the effect of rapamycin (a macrolide antibiotic with potent antirejection
      activity) on the proliferation of fetal cardiac myocytes. Our data suggest that
      rapamycin inhibits the proliferation of these cells, which is an effect that
      appears to be irreversible. This inhibition is relevant to the use of rapamycin
      in the treatment of rejection episodes in the infant and neonate, in which
      cardiac myocyte development is incomplete.

PMID- 9770574
TI  - Exercise tolerance and blood pressure response to exercise testing in children
      and adolescents after renal transplantation.
AB  - The aim of the study was to assess exercise tolerance and blood pressure (BP)
      response to treadmill exercise in children after renal transplantation. Forty
      five children were selected (29 males and 16 females) whose mean age was 14.3 +/-
      4.2 years. All children had Hb >/= 10 g/dl and creatinine clearance >/=40
      ml/min/1.73 m2. They were at least 6 months posttransplantation and were on
      triple immunosuppressive therapy. Twenty-seven were also on various
      antihypertensive medications. Each underwent clinical examination and measurement
      of BP, both at rest and during exercise testing on treadmill. The test was
      stopped on muscular fatigue or exhaustion. The patients were divided into two
      groups: those off (A) or on (B) antihypertensive therapy. When compared to a
      population of healthy children the patients had reduced exercise tolerance (10.1
      +/- 2.1 vs 15.1 +/- 1.7 min, p < 0.001) (67 +/- 16%), increased heart rate (174
      +/- 19 vs 161 +/- 19 beats/min, p < 0.001) (109 +/- 15%), and increased maximum
      systolic BP (150 +/- 26 vs 134 +/- 13 mmHg, p < 0. 001) (113 +/- 19%) at
      comparable workloads. Within the two patient groups, significant differences were
      observed during exercise testing for maximum heart rate, which was lower in group
      B (p = 0.03), and maximum systolic BP, which was higher in group A (p = 0.04).
      Our study confirms that children and adolescents on immunosuppressive therapy
      after renal transplantation have a hypertensive response during exercise,
      probably related to medication-induced peripheral vascular tone.

PMID- 9770575
TI  - Anomalous insertion of the superior or the inferior vena cava into the right
      atrium.
AB  - Three cases with anomalous insertion of the superior or inferior vena cava into
      the right atrium are presented. One case was a 25-year-old healthy man with
      anomalous low insertion of the right superior vena cava into the right atrium.
      The remaining two cases were infants with complex cardiac anomalies showing
      anomalous high insertion of the inferior vena cava into the right atrium. The
      congenital anomalies of the connection between the superior and the inferior vena
      cava and the right atrium are rare. Angiographic and computed tomographic
      findings of these anomalies were reported.

PMID- 9770577
TI  - Historical vignette: tetralogy of Fallot.

PMID- 9770576
TI  - Inhaled nitric oxide therapy in a critically ill neonate with Ebstein's anomaly.
AB  - The successful use of nitric oxide (NO) inhalation in a critically ill neonate
      with Ebstein's anomaly of the tricuspid valve is reported for the first time.
      This use of inhaled NO therapy suggests a therapeutic intervention that directly
      addresses the pathophysiologic process of severe neonatal Ebstein's anomaly.

PMID- 9770578
TI  - Coarctation of the aorta associated with neuroblastoma.

PMID- 9770579
TI  - Severe left ventricular dysfunction and arrhythmias as complications of gram
      positive sepsis: rapid recovery in children.
AB  - Severe left ventricular dilatation and dysfunction in children may be associated
      with poor outcome in as many as 45% of cases. The prognosis for children with
      poor left ventricular function or arrhythmias associated with septic shock may be
      better, however, this has been inadequately studied. We report the favorable
      outcome of three children who presented with Gram-positive sepsis and significant
      cardiovascular compromise-two with severely dilated, poorly contractile left
      ventricle, and one with mild left ventricular dysfunction and incessant,
      malignant, and rapid atrial and ventricular arrhythmias. Our experience with
      these patients shows that complete and rapid resolution of these complications
      may be achieved with aggressive therapy.

PMID- 9770580
TI  - Spontaneous resolution of atrioventricular dissociation in utero.
AB  - Fetal atrioventricular dissociation is a dysrhythmia associated with significant
      antenatal and postnatal morbidity and mortality. We present a case of a 19-week
      old fetus with atrioventricular dissociation, which spontaneously resolved. The
      mother had no signs of autoimmune disease. The fetus had an uneventful gestation
      and, after delivery, had a normal cardiac and transesophageal
      electrophysiological evaluation.

PMID- 9770581
TI  - Double outlet right ventricle with intact atrial septum and restrictive
      ventricular septal defect: an analysis of two cases.
AB  - Two cases of double outlet right ventricle with restrictive ventricular septal
      defect are described. This is an uncommon presentation that causes left
      ventricular dysfunction because of left ventricular outflow tract obstruction.
      The presence of an intact atrial septum leads to severe pulmonary hypertension,
      which tends to aggravate the right ventricular output. In the presence of a
      normal left ventricle, the authors suggest the possibility of enlargement of the
      ventricular septal defect in order to perform a biventricular repair. The
      association of a supramitral valve ring in both cases, and the isolation of the
      left subclavian artery and an aortopulmonary fenestration in one of these cases,
      are also discussed. In addition we explore factors that cause restrictive
      ventricular septal defects as well as the mechanisms that may lead to spontaneous
      closure of ventricular septal defect in a double outlet right ventricle.

PMID- 9770582
TI  - Primary intracardiac yolk sac tumor.
AB  - A 2-year-old male child presented with fever, complete heart block, and
      congestive cardiac failure. Echocardiography showed a dumbbell-shaped mass in the
      right ventricle and right atrium. He was operated on with a provisional diagnosis
      of rhabdomyoma. Histopathology and immunohistochemistry of the resected tumor
      revealed a malignant germ cell tumor with predominant yolk sac differentiation.

PMID- 9770584
TI  - Morphology of the atrioventricular valve in patients with right atrial isomerism.

PMID- 9770583
TI  - Ventricular arrhythmia associated with respiratory syncytial viral infection.
AB  - Respiratory syncytial virus (RSV) is a common cause of lower respiratory
      infections in infants. Cardiac arrhythmias are an uncommon complication in
      infants with RSV bronchiolitis. Presumably, the arrhythmias may be secondary to
      RSV pericarditis, myocarditis, or some other infection of the heart. We report on
      a patient with RSV bronchiolitis who had clinical myocarditis complicated by
      ventricular tachycardia.

PMID- 9770586
TI  - From other journals 

PMID- 9770585
TI  - Percutaneous coil occlusion of ductus arteriosus in absent pulmonary valve and
      intact ventricular septum.

PMID- 9770587
TI  - Upcoming events in pediatric cardiology 

PMID- 9770588
TI  - Pediatric cardiology reviewer acknowledgments 

PMID- 9770589
TI  - Molecular mechanisms of apoptosis regulation 

PMID- 9770590
TI  - ATM et nibrine, proteines partenaires, associees ou independantes de la
      reparation de l'ADN 

PMID- 9770592
TI  - Fiche n 7 : MYCN (N-myc) 

PMID- 9770591
TI  - Unsolved questions about conservative treatment of infiltrating breast carcinoma 
AB  - The majority of patients with breast cancer can be treated by partial mastectomy
      and radiation therapy. The choice of the treatment involves the estimation of the
      risk for intramammary recurrence and the ability to achieve satisfactory cosmetic
      result. Patient selection in breast conserving therapy is dependent on clinical
      and histologic characteristics of the tumor, but many times the therapeutic
      decision is not easy. We present a review of the literature in order to try to
      resolve some contreversed questions about breast conservation in relation to
      tumor size, margin status, tumor location, multicentricity, histologic subtype or
      presence of extensive intraductal component, age of patients and genetic factors.

PMID- 9770594
TI  - Le volume de distribution 

PMID- 9770593
TI  - Multicellular resistance: another mechanism for multidrug resistance? 
AB  - Cells cultured as spheroids present an heterogeneity similar to that of tumours
      in vivo. In the spheroid peripheral layers, cells are proliferating, deeper cells
      are non-cycling, when in the aggregate centre, cells form often a necrotic core.
      A multicellular resistance appears in spheroids, it is a result of the cell
      contact to other cells (homogeneous or heterogeneous cells) and/or to the
      extracellular matrix. The mechanism of this resistance is not known,
      nevertheless, it can be hypothesised to be linked to the spheroid centre hypoxia,
      to the quiescence of a large fraction of the cell population and to the apoptose
      inhibition due to the cell contact. The classical or unicellular mechanisms of
      resistance, as mdr1, MRP, can coexist with the multicellular resistance, but are
      not responsible for this resistance. The spheroid model of culture is a good
      opportunity to study a resistance type which looks close to the tumour resistance
      found in vivo in mice and in patients. A new class of therapeutic molecules
      appears that can reverse this multicellular resistance, inhibit tumours growth
      and preclude metastases. The principal mechanism of action of this new
      pharmacological class appears to be the disruption of the intercellular adhesion
      forces. Preliminary results obtained with these compounds in patients are
      promising.

PMID- 9770595
TI  - Fiche n 6 : bcl2 (B cell lymphoma) 

PMID- 9770596
TI  - What do gastroenterologists, surgeons and oncologists tell patients with colon
      cancer ? results of a survey from the northern france area 
AB  - This regional survey was aimed to detect hypothetical variations in attitudes
      among truth telling in colon cancer by an anonymous questionnaire sent to the 290
      gastroenterologists, surgeons and oncologists of the Northern France area. The
      answers were assessed as always (A), often (O), rarely and never. Diagnosis was
      revealed to the patient (whether or not he asked the question) or to his spouse
      in 83%, 40% and 93% of the cases, respectively. The diagnosis of diffuse
      metastasis was revealed (A + O) to the patient or to his spouse in 23% and 95% of
      the cases, respectively. Only 3% of the physicians told (A + O) the patient that
      his condition was incurable while this aspect was A + O revealed to the patient's
      spouse in 34% of the cases. Most of the time, the diagnosis of colon cancer was
      revealed by oncologists rather than by surgeons or gastroenterologists.
      Conversely the full truth was more commonly told to the family by surgeons and
      gastroenterologists than by oncologists. We found variation in attitudes towards
      truth telling in colon cancer which depend on the physician's speciality. It
      seems to us that the magnitude of the full truth told to the patient or his
      family in Northern France area, is somewhat intermediate between the attitude of
      doctors in Northern Europe and in Latin Mediterranean or Eastern Europe
      countries.

PMID- 9770598
TI  - Traitement adjuvant du cancer du sein localise a haut risque de rechute : et
      maintenant. les diphosphonates 

PMID- 9770597
TI  - How many cancers are cured? 
AB  - One can often read in the lay press that 50% of cancers can be cured. Knowing the
      frequency and the relative 5-year survival rate for each cancer site, one can
      estimate the probability of cure. This estimation is presented for cancers
      diagnosed in 1975, using 5-year survival rates for cancers diagnosed in the
      period 1978-1985. The 5-year survival probability after a diagnosis of cancer is
      37%. The statement that 50% of cancers are cured is too optimistic, and is not
      based on reliable data. One can nevertheless hope to achieve a 50% cure rate in
      the beginning of the xxi-st century.

PMID- 9770599
TI  - Fiche n 5 : hdm2 (mdm2 chez la souris) 

PMID- 9770600
TI  - Remaining indications for total mastectomy in breast carcinoma 
AB  - Does radical mastectomy for cancer remain needed? Breast conserving treatment may
      be achieved by surgery, primary chemotherapy followed by radiotherapy and
      surgery. This article attempts at defining (according to clinical and
      pathological parameters of the tumor and patient's characteristics), when
      conservative treatment is not allowed and radical mastectomy must be performed.
      Mastectomy must be performed first when there are multiple tumors or a tumor too
      large with respect to the breast volume or diffuse microcalcifications on
      mammograms.ometimes the stage of pregnancy, a personal history of collagen
      vascular disease or prior radiotherapy or the willing of the patient lead to
      perform radical mastectomy.econdary mastectomy is necessary in case of failure of
      conservative treatment or recurrence after breast conserving treatment.

PMID- 9770601
TI  - Surgery of lung metastases of breast cancer: analysis of 40 cases 
AB  - Between 1987 and 1995, 52 breast cancer patients had a surgical resection of lung
      secondaries. In 40 patients, the diagnosis of metastatic breast cancer could be
      confirmed following pathological examination. Five-year survival rates of these
      40 patients was 54 8 % and 5-year disease free survival was 30 8%. The median
      survival (70 months) of these patients was better than that of 57 patients with
      isolated lung metastases who had been treated conservately (chemo- or/and
      hormonotherapy) during the same time interval. Twenty-six patients benefitted
      from a radical excision and had a longer disease free interval (42 versus 27
      months, p = 0.03) than patients who had had a wedge resection. Overall survival
      was not significantly different (71 versus 41 months, p = 0.07). We feel that
      isolated lung nodules may best be treated by radical (segment or lobe) excision,
      in particular since preoperative differential diagnosis with primary lung cancer
      may be difficult. In the presence of multiple nodules, first line medical
      treatment by chemo- or hormonotherapy should be advocated, allowing to reduce the
      tumor load and to optimize survival in association with surgery.

PMID- 9770602
TI  - Cylin/CDK inhibitors of the 9p21 chromosomal region and hematological
      malignancies 
AB  - 9p21 chromosomal region contains p15INK4b and p16INK4a genes which regulate G1
      phase of the cell cycle by inhibition of cyclin-cyclin dependent kinases. The
      p19ARF protein is translated from an alternative transcript of the p16INK4a gene
      and regulates G1 and G2 phase of the cell cycle by degradation of the MDM2
      protein. p16INK4a and p15INK4b gene homozygous deletions occur mostly in acute
      lymphoblastic leukemia, ATL secondary to HTLV1 infection, and some lymphoma.
      Point mutations of p16INK4a or p15INK4b gene seem to be extremely rare, however
      selective methylations of the p15INK4b or p16INK4a promoters are frequently found
      in myelodysplastic syndromes and acute leukemias, or lymphomas and myelomas
      respectively. These data demonstrate that inactivation of gene of the 9p21 region
      is currently the main molecular event found in hematological malignancies.

PMID- 9770603
TI  - Mitomycin-vinorelbine as second line chemotherapy in metastatic breast cancer 
AB  - Fourty-six patients (41 evaluable) were treated in second line chemotherapy of
      metastatic breast cancer (MBC) by an association of mitomycin (M), vinorelbine
      (V) (M 8 mg/m2 D1, V 25 mg/m2 D1 and DI 8 every 4 weeks). Median age was 58 years
      (36-78), median performance status 1 (0-3). Thirty-seven per cent of the tumors
      were estrogen receptors positive and 17% progesterone receptors positive.eventeen
      patients received an adjuvant chemotherapy and 39 a first line chemotherapy with
      anthracyclin (A). The median number of metastatic sites was 2 (1-4) and 27
      patients (67%) had visceral metastases. Twelve patients were refractory to
      anthracyclins and 5 resistant. No toxic death nor hemolytic uremic syndrom were
      observed.even (3,7%) febrile neutropenias happened responsible for 4
      hospitalizations. A grade 3 or 4 neutropenia was noted in 34% of the cycles but
      no other clinic toxicity nor grade 3 or 4 thrombopenia. The rate of objective
      response (OR) was 37,5% with 2 complete responses (CR) and 13 partial responses
      (PR).even patients had stable disease and 18 progressed. The rate of hepatic OR
      was 31%. Five (40%) A-refractory patients responded but no resistant patient.
      Median OR time was 10 weeks (8-12) and median OR duration was 5 months (3-6).
      Median survival was 11,5 months. MV association is well tolerated and effective
      in second line chemotherapy for MBC even with hepatic metastasis and in patients
      refractory to anthracyclins.

PMID- 9770604
TI  - Squamous cell carcinoma of the penis 
AB  - Squamous cell carcinoma is the most common tumour of the penis. It is a rare
      disease in Western countries, and occurs in patients after the sixth decade. The
      pattern of spread is loco-regional, and prognosis is poor when nodal metastases
      appear. The etiology of penis cancer is discussed, however human papillomavirus
      infection, tobacco, poor hygiene and phimosis are often associated with this
      disease. Radical surgery gives the best control of the primary tumour, but it is
      mutilating. Conservative therapies (laser, radiotherapy, and particularly
      brachytherapy.) are an attracting option. Regional lymph nodes management is
      extremely controversial. Lymph node metastases, invasion of corpus cavernosum,
      and poor differentiation are pejorative prognostic factors. More than half
      patients are responsive to modern polychemotherpy combinations. However responses
      are transient and chemotherapy alone is not curative for metastatic disease.
      Etiologic factors, clinical presentation, staging work-up requirements,
      prognostic factors and therapeutic modalities are detailed.

PMID- 9770605
TI  - Fiche n 8 : TAL1 (SCL) (T cell leukemia 1) 

PMID- 9770606
TI  - Un membre des complexes SWI/SNF remodelant la chromatine participe a l'oncogenese
      des tumeurs rhabdoides 

PMID- 9770607
TI  - La methylation est un mecanisme frequent d'inactivation des deux copies du gene
      hMLH1 dans les cancers coliques sporadiques 

PMID- 9770608
TI  - Bioelectricity of living tissue.

PMID- 9770609
TI  - Electrophysiologic models of heart cells and cell networks.

PMID- 9770610
TI  - The forward and inverse problems of electrocardiography.

PMID- 9770611
TI  - Theory and applications of body-surface Laplacian ECG mapping.

PMID- 9770612
TI  - Neocortical dynamics of macroscopic-scale EEG measurements.

PMID- 9770613
TI  - EEG dipole source localization.

PMID- 9770614
TI  - High-resolution source imaging of brain electrical activity.

PMID- 9770615
TI  - Electric field stimulation of excitable tissue.

PMID- 9770616
TI  - Resistance of filarial nematode parasites to oxidative stress.
AB  - All filariae examined to date express a comprehensive repertoire of both
      cytoplasmic and secreted anti-oxidant enzymes, although significant differences
      exist between species and life-cycle stages. Adult Brugia malayi, Dirofilaria
      immitis and Onchocerca volvulus secrete CuZn superoxide dismutases, and the
      former two species also secrete a selenocysteine-independent glutathione
      peroxidase. This enzyme has been localised to the cuticular matrix of B. malayi,
      and the preferential reduction of fatty acid- and phospholipid hydroperoxides
      suggests that it may protect cuticular membranes from oxidative damage rather
      than directly metabolise hydrogen peroxide. Adult O. volvulus may compensate for
      an apparent deficiency in expression of this enzyme via a secreted variant of
      glutathione S-transferase. Recent studies have identified a highly expressed
      family of enzymes collectively termed peroxiredoxins, which most probably play an
      essential role in reduction of hydroperoxides. Data from cDNA cloning exercises
      indicate that all filarial species examined thus far express at least two
      peroxiredoxin variants which have been localised to diverse tissues. In-vitro
      studies have shown that B. malayi are particularly resistant to oxidative stress,
      and that the parasites do not rely solely on enzymatic mechanisms of defence.
      Cuticular lipids are relatively resistant to lipid peroxidation due to the low
      unsaturation indices of the constituent fatty acyl residues, but complete
      protection is afforded by the presence of alpha-tocopherol, presumably
      assimilated from host extracellular fluids. Brugia malayi are also relatively
      resistant to nitric oxide-mediated toxicity, and this may be due in part to
      incomplete dependence on aerobic metabolism. Little is known of potential
      mechanisms for detoxification of nitric oxide derivatives and adaptive responses
      to oxidative stress in general, and these represent goals for future research.

PMID- 9770618
TI  - Molecular comparison of Giardia lamblia isolates.
AB  - Giardia lamblia (also Giardia duodenalis, Giardia intestinalis) isolates have
      been variably divided into two or three genotypes by different investigators. We
      have compared the triose phosphate isomerase sequences of the three genotypes
      (Groups 1, 2, and 3) described by Nash and shown that Groups 1 and 2 are similar,
      while Group 3 is markedly different from Groups 1 and 2, indicating that Group
      1/2 and Group 3 correspond to the two major genotypes identified by other
      investigators. We have also analysed three Chinese isolates and showed that two
      fit into Group 3, while the third contained a mixture of Groups 1 and 3 isolates.
      These results confirm the relatedness of G. lamblia isolates from throughout the
      world, and established the feasibility of using DNA amplification and sequence
      analysis for detecting mixed isolates.

PMID- 9770617
TI  - Identification and characterisation of early reactions of asparagine-linked
      oligosaccharide assembly in Entamoeba histolytica.
AB  - Sequential incubation of a mixed membrane fraction isolated from Entamoeba
      histolytica trophozoites with the nonionic detergents Brij 35 and Igepal CA-630
      rendered a soluble fraction with the ability to transfer N-acetylglucosamine
      (GlcNAc) from UDP-GlcNAc to dolichol phosphate to form a lipid saccharide that
      was identified as a mixture of dolichol-P-P-GlcNAc and dolichol-P-P-(GlcNAc)2 as
      follows. (a) The reaction occurred only in the presence of exogenously added
      dolichol phosphate and was strongly inhibited by tunicamycin and amphomycin; (b)
      Over 90% of the aminosugar moiety of the lipid saccharide was released by mild
      acid hydrolysis and was identified as a mixture of GlcNAc and diacetylchitobiose
      [(GlcNAc)2]; (c) Time course experiments revealed that dolichol-P-P-(GlcNAc)2
      accumulated at the expense of a parallel decrease in dolichol-P-P-GlcNAc
      revealing the tandem operation of UDPGlcNAc:dolichol-P GlcNAc-1-P transferase and
      UDPGlcNAc:dolichol-P GlcNAc transferase. Mg2+ and to a lower extent Mn2+ were
      required for catalytic activity and were optimal at 2.5 mM and 1.25 mM,
      respectively. Common phospholipids with different head groups failed to increase
      catalytic activity and phosphatidylglycerol was inhibitory. At low concentration,
      nucleotides such as ATP, GMP and GTP brought about stimulations of 24-54% but
      higher concentrations were inhibitory. Others were inhibitory at all
      concentrations the strongest being those containing a uridine base.

PMID- 9770619
TI  - Variation between hosts in the developmental success of the free-living stages of
      trichostrongyle infections of sheep.
AB  - Variation between hosts of different ages and genotypes in the developmental
      success of trichostrongylid parasite eggs from sheep was investigated in two
      trials. The percentage development to infective third-stage larvae of eggs
      collected from lambs and adult ewes infected with Ostertagia circumcincta was
      compared in an indoor trial. In addition, sheep previously bred for either high
      or low faecal egg count and grazed outdoors on parasite contaminated pasture were
      sampled; egg development, faecal egg count, generic profile and faecal dry matter
      were measured. In both trials, development to L3 was significantly lower in eggs
      derived from adult ewes than from lambs and, in the field trial, from animals
      selected for low faecal egg count. The observed differences could not be
      accounted for by variations in faecal egg count, faecal dry matter content nor by
      differences in the generic composition of worm egg output. Although not shown
      conclusively, the results are consistent with an immune mechanism influencing the
      development of free-living stages of gastrointestinal nematodes outside the host.
      These results have significant implications for our understanding of parasite
      epidemiology, particularly as it relates to sources of pasture contamination.

PMID- 9770620
TI  - Effect of anti-immunoglobulin antibodies produced in cattle infected with
      Trypanosoma evansi on antigen detection ELISA.
AB  - The possibility of interference with the antigen-detection ELISA for
      trypanosomosis by anti-rodent IgG antibodies produced in cattle infected with
      Trypanosoma evansi was investigated. Two different ELISA for detection of
      trypanosome antigen and three different systems for anti-rodent IgG antibody
      detection were established. The former two were respectively polyclonal antibody
      based and a combination of monoclonal and polyclonal antibody-based assays. The
      latter three were also adapted for detection of anti-mouse IgG, anti-rabbit IgG
      and anti-IgG antibodies cross-reactive with both rabbit and mouse IgGs. A total
      of 170 samples were collected from a dairy cattle farm where an outbreak of T.
      evansi infection was reported. One hundred and two cattle (59%) were found to be
      positive for trypanosome antigens by the polyclonal antibody-based assay and 86
      (51%) were positive by the combination-based system. On the other hand, 51 (30%)
      and 10 (6%) of cattle had anti-rabbit and anti-mouse IgG antibodies respectively
      but none had antibodies cross-reactive with both IgGs. Of the 102 cattle positive
      for trypanosome antigens in the polyclonal antibody-based ELISA, 48 (47%) were
      also anti-rabbit IgG antibody positive. It is concluded that antigen detection
      ELISA based on a single-species immunoglobulin for capture and detection might
      misdiagnose T. evansi infection. Results indicate that this bias will be avoided
      if reagents for capture and detection are derived from different species.

PMID- 9770621
TI  - Identification of a human isolate of Encephalitozoon cuniculi type I from Italy.
AB  - A microsporidial strain, obtained from a person with AIDS living in Italy was
      isolated and cultivated on RK13 (rabbit kidney) cell monolayers. Identification
      at the species level was performed by immunological and molecular methods.
      Western blot analysis showed that the human isolate and the Encephalitozoon
      cuniculi reference strain had similar banding patterns. The small subunit rRNA
      sequence analysis confirmed the identification of the isolate as E. cuniculi,
      which is a widespread microsporidian species infecting a wide range of natural
      hosts, including humans. Moreover, based on the sequence of the rDNA internal
      transcribed spacer region, this isolate was classified as E. cuniculi type I
      (rabbit strain), previously reported in six persons with AIDS living in
      Switzerland. These results provide further information on the geographical
      distribution of E. cuniculi types.

PMID- 9770622
TI  - Restriction fragment length polymorphism and virulence of Czech Toxoplasma gondii
      strains.
AB  - Restriction fragment length polymorphism analysis of chromosomal DNA from 22
      strains of Toxoplasma gondii were characterised using SalI and PstI restriction
      endonucleases and the TGR1E specific repetitive sequence as a probe. Two virulent
      strains, RH and P-CZ, had previously been isolated from humans, the remaining 20
      strains were isolated from animals in the Czech Republic in 1994 and 1995. Among
      the 20 recently isolated strains, 19 belonged to an avirulent lineage and only
      one strain from the wild cat Felis silvestris belonged to a virulent lineage.

PMID- 9770623
TI  - Developmental expression of a Fasciola hepatica sequence homologous to ABC
      transporters.
AB  - Polymerase chain reaction and cDNA library screening approaches were employed to
      identify a putative member of the highly conserved family of ATP-binding cassette
      transport proteins from Fasciola hepatica. At the predicted protein level, the F.
      hepatica sequence identified in the present study shares 43% and 36% identity
      with the Schistosoma mansoni SMDR2 and human MDR1 ATP-binding cassette transport
      sequences, respectively. Northern blot and reverse transcriptase-PCR analyses
      have demonstrated that expression of the F. hepatica ABC-transporter homologue is
      confined to immature parasites. The biochemical basis for the stage-specific
      expression of the ATP-binding cassette transporter homologue within F. hepatica
      remains to be determined.

PMID- 9770624
TI  - Infection of sheep with adult and larval Ostertagia circumcincta: abomasal
      morphology.
AB  - The infection of parasite-naive sheep with approximately 15,000 adult Ostertagia
      circumcincta via abomasal cannulae resulted in marked changes in the structure
      and function of the abomasum. The functional changes, which have been
      characterised previously, included elevated abomasal pH and increased serum
      concentrations of pepsinogen and gastrin. Eight days after the transplant of
      adult worms, the abomasa of recipient animals were significantly heavier than
      those of controls (P < 0.001), the thickness of the fundic mucosa was greater (P
      < 0.01), there were fewer parietal cells (P < 0.01) and increases in the numbers
      of mitotic figures and mucus-producing cells. Mucous cell hyperplasia was also
      evident in the fundic mucosae of sheep receiving a trickle infection of
      infective, third-stage O. circumcincta larvae and was prominent within nodules
      associated with larval development. In non-nodular mucosa, there was hyperplasia
      of mucous cells and changes in the distribution of parietal cells. Decreases in
      the number of parietal cells at the gland base were offset by increases at a mid
      gland level, probably due to chronic hypergastrinaemia, so that, overall, total
      parietal cell number was unaffected. Mucous cell hyperplasia and the diminution
      of parietal cell number are seen in a diverse range of disease states and may be
      mediated by host growth factors such as Transforming growth factor-alpha.
      Alternatively, the cellular and/or the secretory changes in response to the
      presence of adult worms are mediated by chemicals that are cytotoxic/inhibitory
      for parietal cells, and released by the parasites themselves.

PMID- 9770625
TI  - Infection of sheep with adult and larval Ostertagia circumcincta: gastrin.
AB  - Gastric endocrine cell populations and serum and tissue gastrin have been
      examined in sheep which were infected either intraruminally by tube with 150,000
      Ostertagia circumcincta larvae followed by a trickle infection of 10,000 larvae
      thrice weekly for 8 weeks or by the transfer of 15,000 adult worms directly into
      the abomasum and killed 8 days later. Depletion of both antral gastrin and
      somatostatin was evident in both groups: tissue gastrin concentrations were
      reduced by 85% in the trickle infection and both G cells (gastrin-containing) and
      D cells (somatostatin-containing) were pale and fewer after adult worm transfer.
      The concurrent depletion of antral gastrin and somatostatin supports the
      contention that the hypergastrinaemia in parasitised sheep is largely secondary
      to the increase in abomasal pH. Although there was no change in the proportions
      of G34 and G17 in the tissues, there was an increase in the longer form of
      gastrin in the circulation of the larval-infected sheep, suggesting that there
      may be differential secretion of G17 and G34 which may be exaggerated as the rate
      of secretion increases. Although the fundic mucosa was thicker following trickle
      infection, there was no evidence of enterochromaffin-like cell hyperplasia in
      either infected group. It is suggested that hyper-gastrinaemia may be beneficial
      to the host, as it may allow the abomasum to regain the ability to acidify its
      contents during continued exposure to the parasites.

PMID- 9770626
TI  - Use of the ITS rDNA for elucidation of some life-cycles of Mesometridae
      (Trematoda, Digenea).
AB  - Identification of larval stages is crucial for elucidating the life-cycles of
      various Digenea. However, in many digenean species, the larvae lack distinctive
      morphological features and it is impossible to establish the affiliation between
      the larval and adult stages by using morphological criteria. Molecular methods,
      based on DNA sequencing or PCR-restriction fragment length polymorphism analysis,
      can offer a new tool for larval-stage identification. In this study, the
      sequences of internal transcribed spacer of the ribosomal DNA were used to
      identify the cercariae of three out of five species of the family Mesometridae
      (Centroderma spinosissima, Elstia stossichianum and Wardula capitellata). The
      three species differ from one another by number of repeats in the region of
      internal transcribed spacer 1. The phylogeny of Mesometridae was inferred from
      their internal transcribed spacer ribosomal DNA sequences. The PCR-linked
      restriction fragment length polymorphism approach was developed for future life
      cycle and ecological studies of this family.

PMID- 9770627
TI  - Symbioses in Amphipholis squamata (Echinodermata, Ophiuroidea, Amphiuridae):
      geographical variation of infestation and effect of symbionts on the host's light
      production.
AB  - Populations of the polychromatic and bioluminescent species Amphipholis squamata
      from eight locations were examined for internal and external symbionts. At three
      locations (two in the United Kingdom and one in Papua New Guinea), no symbionts
      were present, while four species were recovered from the remaining locations:
      Cancerilla tubulata and Parachordeumium amphiurae (copepods), Rhopalura
      ophiocomae (orthonectid) and an undescribed species of rhabdocoel turbellarian.
      No ophiuroid individual hosted more than one symbiont species, despite the
      presence of two or more within a population. Symbiont presence and prevalence
      varied with location, and with colour variety, but with no apparent pattern or
      trends. Light-production characteristics of the host were affected by the
      presence of all symbionts except C. tubulata. These effects, however, did not
      vary between colour varieties or between geographical locations, but were
      specific to the symbiont species: the presence of P. amphiurae resulted in
      enhanced intensity of light production, while that of R. ophiocomae and the
      turbellarian species resulted in reduced intensity. The kinetics of light
      production (time until maximum output) were altered only by the presence of the
      turbellarian. Changes in the light-production characteristics are discussed in
      relation to morphological, energetical and physiological effects of the
      symbioses.

PMID- 9770628
TI  - Molecular characteristation of digenetic trematodes associated with Cyathura
      carinata (Crustacea: Isopoda) with a note on the utility of 18S ribosomal DNA for
      phylogenetic analysis in the Digenea (Platyhelminthes: Trematoda).
AB  - Analysis of 18S rDNA sequences isolated from Cyathura carinata (Crustacea:
      Isopoda) indicate that two different species of the Digenea (Platyhelminthes:
      Trematoda) parasitize this isopod species for which parasitic associations have
      previously been unknown. Phylogenetic analysis, based on the largest data set of
      digenetic 18S rDNA sequences published to date, also suggests that 18S rDNA is
      unsuitable for the reconstruction of phylogenetic relationships of the major
      digenetic lineages either due to rapid radiation of these lineages or the
      presence of homoplasy at this level.

PMID- 9770629
TI  - Babesia canis infection in canine-red blood cell-substituted SCID mice.
AB  - We have developed a mouse model for Babesia canis infection using severe combined
      immunodeficiency (SCID) mice whose circulating red blood cells had been
      substituted with canine red blood cells. Substitution of red blood cells in SCID
      mice was achieved by repetitive transfusions of canine red blood cells, together
      with administration of an antimouse red blood cell monoclonal antibody. Following
      inoculation of canine-red blood cell-SCID mice with B. canis, parasites
      proliferated in the canine red blood cells that had been transfused into the SCID
      mice, resulting in much higher parasitaemia than that observed in dogs. In an
      attempt to demonstrate the utility of this mouse model, three antiprotozoal
      drugs, diminazene diaceturate, clindamycin and oxytetracycline, were examined for
      their efficacy to inhibit the growth of B. canis in canine-red blood cell-SCID
      mice. The mouse model clearly showed that diminazene diaceturate and
      oxytetracycline were capable of eliminating B. canis from the canine-red blood
      cell-SCID mice, whereas clindamycin exhibited only a static effect as
      parasitaemia relapsed upon cessation of drug administration.

PMID- 9770630
TI  - Immunolocalisation of the glutathione S-transferases, GST-26 and GST-28, within
      adult Schistosoma japonicum.
AB  - This paper describes the first ultrastructural immunolocalisation study of the 26
      kDa and 28-kDa glutathione S-transferases within adult Schistosoma japonicum (GST
      26 and GST-28). Polyclonal antibodies raised against GST-28 (in mice) and against
      GST-26 (in rabbits) were used to examine the distribution of the proteins within
      adult parasites. Both proteins were localised within the parenchymal region of
      the male parasite. Additionally, both proteins were present within parenchymal
      cells located between the vitelline glands of female parasites. There were no
      detectable levels of GST-26 or GST-28 on the surface or within the tegument
      matrix of either the male or female worms. Possible functions for GST-26 and GST
      28 within S. japonicum and their significance as vaccine target molecules are
      addressed.

PMID- 9770631
TI  - Ultrastructural analysis of the adult Schistosoma japonicum by lectin
      cytochemistry.
AB  - Eight lectin probes were used to detect a range of carbohydrate residues in the
      tegument matrix of Schistosoma japonicum. In addition, other areas of the
      parasite, such as the gut, vitelline glands and flame cells, were examined for
      carbohydrate residues. Some minor differences in the carbohydrate residue
      composition between tegument orientations and between the sexes were identified.
      Differences between the distribution of carbohydrate residues of S. japonicum
      examined in this study and previous reports of Schistosoma mansoni were also
      noted. This study further illustrates the high level of complexity within the
      tegument of the adult S. japonicum and has demonstrated differences between this
      species and the widely studied S. mansoni.

PMID- 9770632
TI  - Ultrastructure of spermiogenesis of Dipylidium caninum (Cestoda, Cyclophyllidea,
      Dipylidiidae), an intestinal parasite of Canis familiaris.
AB  - We describe for the first time the ultrastructure of spermiogenesis of a
      representative of the family Dipylidiidae, Dipylidium caninum. Spermiogenesis
      begins with the formation of a differentiation zone. This conical area presents
      two centrioles with associated striated roots. One of the centrioles develops a
      flagellum and posteriorly a proximodistal fusion is produced between the axoneme
      and a median cytoplasmic process. In a final stage of spermiogenesis a
      condensation of electron-dense material between cortical microtubules is observed
      in the anterior part of the differentiation zone. This is the origin of the crest
      like body that appears at the end of spermiogenesis. The presence of striated
      roots associated with centrioles constitutes the first report of these structures
      in the spermiogenesis of a cyclophyllidean cestode.

PMID- 9770633
TI  - Detection of Toxoplasma gondii in tissues of sheep orally challenged with
      different doses of oocysts.
AB  - The presence of Toxoplasma gondii in blood, brain, cardiac muscle and skeletal
      muscle (gracillis and psoas) of sheep 6 weeks after experimental infection with
      10(5), 10(4) and 10(3) T. gondii oocysts was determined using the PCR technique.
      The study demonstrates that oral infection of sheep with T. gondii oocysts of the
      M3 isolate results in parasites being detectable in tissues 6 weeks p.i. The PCR
      detection was much more sensitive than histological detection. Parasite DNA was
      detected more frequently and consistently in the group of sheep given 10(5)
      oocysts compared with those given 10(3) oocysts. The brain and heart were most
      frequently infected compared with the other tissues.

PMID- 9770634
TI  - Oral Neospora caninum inoculation of neonatal calves.
AB  - Four calves born to cows seronegative for Neospora caninum were dosed orally
      within 6 h after birth with tachyzoites of the bovine N. caninum Nc-SweB1 isolate
      added to colostrum. Two of the calves were dosed via stomach tube and two by
      feeding bottle. The latter two calves showed transient fever and passed blood
      stained diarrhoea 1-2 weeks after inoculation. From 5 weeks after inoculation
      they developed a significant antibody response which remained high until the
      calves were euthanised and necropsied at 15 and 19 weeks after inoculation,
      respectively. The two calves inoculated by stomach tube showed no clinical signs
      and they remained seronegative throughout the study. At necropsy of the
      seropositive calves, no pathological lesions were seen, and parasites were not
      detected by immunohistochemistry. Neospora caninum was not re-isolated in cell
      culture from the brains of the seropositive calves; however, N. caninum DNA was
      detected in brain from both of them by PCR. The data suggest that oral infection
      of N. caninum via colostrum might be a possible route of vertical transmission in
      newborn calves, in addition to transplacental infection.

PMID- 9770635
TI  - Dogs are definitive hosts of Neospora caninum.
AB  - Dogs were investigated to determine if they are definitive hosts of Neospora
      caninum. Four dogs were fed N. caninum tissue cysts in infected mouse tissue, and
      two negative control dogs were fed uninfected mouse tissue. Dog faeces were
      examined daily for 30 days using a sucrose flotation technique. Three challenged
      dogs shed spherical to subspherical unsporulated oocysts, measuring 10 to 11
      microns in diameter. Oocysts sporulated within 3 days and contained two
      sporocysts, each with four sporozoites. Outbred, inbred, and gamma-interferon
      knockout mice were inoculated with canine faecal extracts and monitored for
      evidence of neosporosis using a variety of morphologic, immunohistologic,
      serologic, and genetic analyses. Mice that received faeces from each dog observed
      to shed oocysts were demonstrated to have neosporosis by two or more techniques.
      One mouse was demonstrated to be infected with N. caninum by
      immunohistochemistry, ultrastructural analysis, and a species-specific PCR test.
      No evidence of neosporosis was observed in control animals. Based on this study,
      dogs are a definitive host of Neospora caninum.

PMID- 9770636
TI  - A model for collaboration in quality improvement projects: implementing a weight
      based heparin dosing nomogram across an integrated health care delivery system.
AB  - BACKGROUND: At Aurora Health Care, an integrated delivery system based in
      Milwaukee, a system-level clinical quality improvement department was established
      in 1995 to facilitate collaboration on clinical quality improvement (QI)
      initiatives. THE COLLABORATIVE MODEL: A model was developed to use expertise
      within the system and avoid unnecessary duplication of efforts, while maintaining
      buy-in for the project's interventions at the point of service delivery. It was
      believed that a single team could design the improvement efforts or guidelines,
      and then work at a more local level with a different group of people to implement
      the processes. APPLYING THE MODEL TO THE HEPARIN QI PROJECT: Anticoagulation with
      heparin is considered the mainstay of treatment for pulmonary embolism and deep
      venous thrombosis. However, a large gap was found between present anticoagulation
      practices and published best practice in regards to achieving a key process
      measure. To reduce the overall time to achieving effective anticoagulation, a
      system-level team created an intervention primarily consisting of a preprinted
      order sheet, including the weight-based heparin dosing nomogram, and an education
      plan for physicians and other health care professionals. Significant improvement
      was observed at all pilot sites with overall rates of adequate anticoagulation
      within the first 24 hours improving from 73% to 95%. DISCUSSION: The system was
      able to standardize care at four of its five major hospitals and provide for
      better patient outcomes to a larger segment of the community, and then to
      replicate the heparin project to four additional sites during a six-month period.
      This model has been successfully applied to other quality improvement projects.

PMID- 9770637
TI  - Choosing and evaluating clinical performance measures.
AB  - BACKGROUND: The importance and utility of routine externally reported assessments
      of the quality of health care delivered in managed care organizations and
      hospitals have become widely accepted. Because externally reported measures of
      quality are intended to inform or lead to action, proposers of such measures have
      a responsibility to ensure that the results of the measures are meaningful,
      scientifically sound, and interpretable. CRITERIA FOR SELECTING MEANINGFUL
      ASSESSMENT AREAS: In choosing clinical performance measures to distinguish among
      health plans, the condition should have a significant impact on morbidity and/or
      mortality; the link between the measured processes and outcomes of care should
      have been established empirically; quality in this area should be variable or
      substandard currently; and health plans and/or providers should be able to take
      clinically sensible actions to enhance performance on the measure. CRITERIA FOR
      ASSESSING SCIENTIFIC SOUNDNESS: Scientific soundness--the likelihood that a
      clinical performance measure will produce consistent and credible results when
      implemented--involves precision of specifications, adaptability, and adequacy of
      risk adjustment. INTERPRETABILITY OF RESULTS: Interpretability is affected by the
      content of the measure and the audience. Measures that are clinically detailed
      and specific may be presented more generally to a consumer audience and in full
      detail to a clinical audience, but measures that are general by nature cannot be
      made more clinically detailed. Interpretability entails statistical analysis,
      calibration of measures, modeling, and presentation of information. CONCLUSIONS:
      Increased standardization of both the expectations for public release on measures
      of quality and the criteria by which such measures will be evaluated should
      contribute to improvements in the larger field of quality assessment.

PMID- 9770638
TI  - Improving care for acute myocardial infarction: experience from the Cooperative
      Cardiovascular Project. The Cooperative Cardiovascular Project Best Practices
      Working Group.
AB  - BACKGROUND: The Cooperative Cardiovascular Project (CCP) was initiated by the
      Health Care Financing Administration to improve the quality of care for Medicare
      beneficiaries admitted to the hospital with acute myocardial infarction (AMI).
      Four peer review organizations formed the CCP Best Practices Working Group
      (Working Group) to identify effective intervention strategies that enable a
      hospital staff to improve AMI care. METHODS: The peer review organization in each
      state was asked to identify six hospitals with exemplary quality improvement (QI)
      plans for AMI care; 33 states responded. Data about the hospitals' baseline
      performance on the CCP quality indicators and components of the QI plans were
      collected from each hospital. Thirty-six of 40 randomly selected hospitals from
      this group were interviewed. RESULTS: The Working Group identified 191 hospitals
      in 33 states with exemplary QI plans. Administration of thrombolytic therapy and
      aspirin were the quality indicators most commonly addressed. Staff education,
      development or revision of clinical pathways and standing orders, and ongoing
      data collection were the most common QI plan components. The need to develop
      interdisciplinary teams and to identify a strong physician champion for the QI
      efforts were the most common recommendations for other hospitals considering
      implementation of the CCP. CONCLUSIONS: The CCP stimulated interest in QI
      activities for AMI care in the institutions identified for the Working Group. The
      characteristics of the hospitals' improvement plans were consistent with those
      identified by contemporary leaders of clinical QI as central to improving care.
      These plans focused on changes in clinical processes, deployment of
      interdisciplinary teams, identification of project champions, and ongoing data
      collection to assess and improve quality of care.

PMID- 9770639
TI  - Public disclosure of performance information in Pennsylvania: impact on hospital
      charges and the views of hospital executives.
AB  - BACKGROUND: Forty states have now passed legislation establishing governmental
      agencies charged with the task of gathering hospital-level data. Since 1988 all
      acute care hospitals in Pennsylvania have been submitting data to the
      Pennsylvania Health Care Cost Containment Council (PHC4). Pennsylvania's policy
      was designed to make patients and purchasers more informed and selective buyers
      of medical services, to increase the public accountability of providers of these
      services, and to encourage hospitals and physicians to compete more on clinical
      outcomes and charges. The impact of Pennsylvania's policy of public disclosure of
      performance information on hospital charges over time has not previously been
      evaluated. Nor has the importance that hospital executives assign to the
      publication of comparative charges and clinical outcomes information been
      assessed. METHODS: From 1990 through 1994 the PHC4 published a number of hospital
      level performance reports (including the regional Hospital Effectiveness Reports
      and A Consumer's Guide to Coronary Artery Bypass Graft Surgery) containing
      hospital average charges, average lengths of stay, a rating of severity of
      illness, and two outcome measurements--morbidity and in-hospital mortality--on a
      total of 59 diagnosis-related groups. An 18-item survey designed to assess
      hospital executives' opinions of the usefulness and importance of the PCH4
      information was sent to the chief executive officers at the study hospitals.
      DISCUSSION: There were no significant trends toward a reduction in the dispersion
      of charges in either category of hospitals during the study period. Most hospital
      executives assigned low ratings of importance to published comparative charges
      information; however, executives of high-competition hospitals assigned
      significantly higher importance ratings to the information as a whole in
      enouraging hospital competition based on quality.

PMID- 9770640
TI  - Advances in the molecular characterization of tryptophan hydroxylase.
AB  - The neurotransmitter serotonin has been implicated in numerous physiological
      functions and pathophysiological disorders. The hydroxylation of the aromatic
      amino acid tryptophan is rate-limiting in the synthesis of serotonin. Tryptophan
      hydroxylase (TPH), as the rate-limiting enzyme, determines the concentrations of
      serotonin in vivo. Relative serotonin concentrations are clearly important in
      neural transmission, but serotonin has also been reported to function as a local
      antioxidant. Identification of the mechanisms regulating TPH activity has been
      hindered by its low levels in tissues and the instability of the enzyme. Several
      TPH expression systems have been developed to circumvent these problems. In
      addition, eukaryotic expressions systems are currently being developed and
      represent a new avenue of research for identifying TPH regulatory mechanisms.
      Recombinant DNA technology has enabled the synthesis of TPH deletions, chimeras,
      and point mutations that have served as tools for identifying structural and
      functional domains within TPH. Notably, the experiments have proven long-held
      hypotheses that TPH is organized into N-terminal regulatory and C-terminal
      catalytic domains, that serine-58 is a site for PKA-mediated phosphorylation, and
      that a C-terminal leucine zipper is involved in formation of the tetrameric
      holoenzyme. Several new findings have also emerged regarding regulation of TPH
      activity by posttranslational phosphorylation, kinetic inhibition, and covalent
      modification. Inhibition of TPH by L-DOPA may have implications for depression in
      Parkinson's disease (PD) patients. In addition, TPH inactivation by nitric oxide
      may be involved in amphetamine-induced toxicity. These regulatory concepts, in
      conjunction with new systems for studying TPH activity, are the focus of this
      article.

PMID- 9770642
TI  - Function of the N-acetyl-L-histidine system in the vertebrate eye. Evidence in
      support of a role as a molecular water pump.
AB  - N-acetyl-L-histidine (NAH) is a major constituent of poikilotherm brain, eye,
      heart, and muscle, but for which there is no known function. NAH is characterized
      by high tissue concentrations, a high tissue/extracellular fluid (ECF) gradient,
      and by a continuous selective and regulated efflux into ECF. In the eye, there is
      a complete compartmentalization of the synthetic and hydrolytic enzymes, with
      synthesis of NAH from AcCoA and L-histidine (His) occurring in the lens, and its
      hydrolysis to acetate and His restricted to surrounding ocular fluids. Using 14C
      isotopes, the cycling of NAH between lens and ocular fluids in a simple support
      medium consisting of NaCl (0.9%), Ca2+ (4 mEq/L) and D-glucose (5 mM) at pH 7.4
      has previously been observed. In the present study, using the isolated lens of
      the goldfish eye, each of the components of that support medium has been
      individually varied in order to determine its effect on NAH release down its
      intercompartmental gradient. As a result of these and related studies, it is
      suggested that NAH may function as a metabolically recyclable gradient-driven
      molecular water pump. It is proposed that water influx or generation of metabolic
      water serves as the trigger mechanism to open a Ca-dependent gate for the release
      of NAH down its gradient, along with its associated water. Preliminary analyses
      suggest that in addition to its potential for multiple daily cycles, a strongly
      ionized hydrophilic molecule, such as NAH, may include a large power function as
      a result of its attraction to water, and it has been calculated that an aqua
      complex of each NAH molecule may have 33 dipole-dipole-associated water molecules
      as it passes into ECF. It is this unique combination of a capacity for multiple
      cycles per day, coupled with a large power function, that may allow for such an
      intracellular osmolyte to be present in relatively low concentration in
      comparison to total cellular osmolality, and yet to perform a large and important
      task with little expenditure of energy. With each NAH molecule recycled up to 10
      times/d, and a power factor of 33, there could be 330 mmol of water
      transported/mmol of NAH each day. With typical NAH concentrations in brains of
      poikilothermic vertebrates of 5-10 mmol/kg, there is the potential for up to 3.3
      mol (60 mL) of water to be removed each day/kg of brain, a value that represents
      about 8% of total brain water content. Dewatering of the released osmolyte would
      occur in two additional steps, consisting of its hydrolysis and the subsequent
      active uptake of its metabolites. It is also suggested that NAH is the archetype
      of several metabolically and structurally related cellular osmolytes found in
      both poikilotherms and homeotherms, for which there is similarly no known
      function, and these may form a family of cycling hydrophilic osmolytes that serve
      as molecular water pumps in a variety of tissues. These include the basic His
      containing derivatives: NAH, carnosine, anserine, ophidine, and homocarnosine,
      and the acidic aspartate derivatives: N-acetyl-L-aspartate (NAA) and N-acetyl-L
      aspartylglutamate (NAAG). In each of these cases, the high
      intracellular/extracellular osmolyte gradient appears to be maintained by
      combining a hydrophilic protein amino acid with a nonprotein moiety to block its
      use in other intracellular metabolic pathways, and by blocking catabolism of the
      derivative by maintaining its hydrolytic enzyme in an extracytosolic membrane or
      extracellular compartment. Unlike other known water-regulating mechanisms, the
      proposed cellular system is unique in that as a water pump, it can function as a
      water regulator independently of extracellular solute composition or osmolality.
      Finally, based on the hypothesis developed, the NAH system would represent the
      first cellular water pump to be identified.

PMID- 9770641
TI  - Amyloid beta-peptide (1-40)-mediated oxidative stress in cultured hippocampal
      neurons. Protein carbonyl formation, CK BB expression, and the level of Cu, Zn,
      and Mn SOD mRNA.
AB  - Mechanism of amyloid beta-peptide (A beta) toxicity in cultured neurons involves
      the development of oxidative stress in the affected cells. A significant increase
      in protein carbonyl formation was detected in cultured hippocampal neurons soon
      after the addition of preaggregated A beta(1-40), indicating oxidative damage of
      proteins. We report that neurons, subjected to A beta(1-40), respond to A beta
      oxidative impact by activation of antioxidant defense mechanisms and alternative
      ATP-regenerating pathway. The study demonstrates an increase of Mn SOD gene
      expression and the restoration of Cu, Zn SOD gene expression to a normal level
      after temporary suppression. Partial loss of creatine kinase (CK) BB activity,
      which is the key enzyme for functioning of the creatine/phosphocreatine shuttle,
      was compensated in neurons surviving the A beta oxidative attack by increased
      production of the enzyme. As soon as the oxidative attack triggered by the
      addition of preaggregated A beta (1-40) to rat hippocampal cell cultures has been
      extinguished, CK BB expression and SOD isoenzyme-specific mRNA levels in
      surviving neurons return to normal. We propose that the maintenance of a constant
      level of CK function by increased CK BB production together with the induction of
      antioxidant enzyme gene expression in A beta-treated hippocampal neurons accounts
      for at least part of their adaptation to A beta toxicity.

PMID- 9770643
TI  - Inhibition of antagonist and agonist binding to the human brain muscarinic
      receptor by arachidonic acid.
AB  - Arachidonic acid (AA) inhibits the binding of [3H]quinclidinyl benzilate
      ([3H]QNB) to the human brain muscarinic cholinergic receptor (mAChR). AA inhibits
      at lower concentrations in the absence of glutathione (I50 = 15 microM) than in
      the presence of glutathione (I50 = 42 microM). Inhibition of mAChR binding shows
      specificity for AA and is reduced with loss of one or more double bonds or with
      either a decrease or increase in the length of the fatty acid chain. Metabolism
      of AA by the lipoxygenase, epoxygenase, or fatty acid cyclooxygenase pathways is
      not required for the inhibitory activity of AA on mAChR binding. Inhibition of
      [3H]QNB binding by AA is reversible. While decreasing Bmax, AA increased the
      apparent KD for [3H]QNB and for the more polar antagonist [3H]NMS. In addition,
      AA inhibits binding of the agonist [3H]oxotremorine-M (I50 = 60 microM) and is
      the first mediator of mAChR action to be shown to reversibly inhibit mAChR
      binding. The feedback inhibition of the mAChR by AA may serve a homeostatic
      function similar to the reuptake and hydrolysis of acetylcholine following
      cholinergic nerve transmission.

PMID- 9770644
TI  - Chronic administration of imipramine and citalopram alters the expression of NMDA
      receptor subunit mRNAs in mouse brain. A quantitative in situ hybridization
      study.
AB  - Chronic administration of antidepressants produces region-specific adaptive
      changes in the radioligand binding properties of N-methyl-D-aspartate (NMDA)
      receptors. We hypothesized that this effect of chronic antidepressant
      administration was owing to an alteration in NMDA receptor subunit composition.
      This hypothesis was examined using in situ hybridization with [35S]-labeled
      riboprobes to quantify the impact of chronic (16 d) injection with either
      imipramine (15 mg/kg) or citalopram (20 mg/kg) on the levels of transcripts
      encoding NMDA receptor subunits in mouse brain. These antidepressants altered the
      levels of mRNA encoding the zeta-subunit in a parallel fashion, with both drugs
      either reducing transcript levels (e.g., in the cortex, cerebellum, thalamus, and
      striatum) or producing no substantial effects (e.g., hippocampus). In contrast,
      these antidepressants often produced distinct, region-specific effects on mRNA
      levels encoding the epsilon family of subunits. For example, citalopram treatment
      produced widespread reductions in epsilon 1-subunit mRNA levels (e.g., in frontal
      cortex, CA2 of hippocampus, and amygdala), whereas imipramine reduced levels of
      this transcript only in the amygdala. Conversely, imipramine treatment produced
      widespread reductions in epsilon 2-subunit mRNA levels (e.g., in cortex, CA1-4 of
      hippocampus, and amygdala), whereas the effects of citalopram on levels of this
      transcript were largely restricted to amygdala. These findings indicate that long
      term antidepressant treatment produces region-specific changes in expression of
      transcripts for NMDA receptor subunits, presumably altering NMDA receptor
      composition. Because subunit composition determines the physiological and
      pharmacological properties of NMDA receptors, these changes may play a critical
      role in the therapeutic actions of structurally diverse antidepressants.

PMID- 9770645
TI  - Structure and upstream region characterization of the human gene encoding rod
      photoreceptor cGMP phosphodiesterase alpha-subunit.
AB  - Rod photoreceptor cGMP phosphodiesterase (PDE6) is a three-subunit (a, b, g2)
      enzyme that functions to reduce intracellular cytoplasmic cGMP levels, an
      integral feature of the phototransduction cascade of vision. To allow assessment
      of the potential for defects in the gene encoding the alpha-subunit (PDE6A) to
      cause visual dysfunction, and to begin to dissect the basis for photoreceptor
      specific expression of this gene, we have characterized the structural gene and
      upstream region. The human PDE6A gene consists of 22 exons spanning about 60 kb
      with the intron/exon junctions highly conserved in comparison to the mouse and
      human PDE6B genes. Using ribonuclease protection and primer extension assays, a
      predominant transcription start point (tsp) was identified 120 bp upstream of the
      initiator ATG. To begin functional analysis of the PDE6A promoter, approx 4 kb of
      sequence were determined upstream of the tsp. Comparison of this upstream
      sequence with an approximately 500 bp sequence upstream of the mouse Pde6a gene
      revealed five distinct segments of identity all within 100 bp upstream of the
      human PDE6A tsp. A TATA box adjacent to a photoreceptor-specific RET1-like
      binding site, an SP1 site, and two novel putative cis-element sequences were
      found. A consensus initiator element sequence is present at the tsp.
      Additionally, within a 2.5-kb segment beginning 900 bp upstream of the tsp two
      Alu, a MIR, an L1, and two MER repetitive elements were found. Electrophoretic
      mobility shift assays generate a retina-specific bandshift using a 322-bp
      fragment containing the putative promoter region or a multimer of the RET1-like
      site. DNA footprinting assays revealed footprints over the primary transcription
      startpoint and the RET1-like and TATA box regions. These results indicate that a
      220-bp segment of the PDE6A gene upstream region is important for tissue-specific
      expression.

PMID- 9770646
TI  - 6-hydroxydopamine lesion of rat nigrostriatal dopaminergic neurons differentially
      affects nicotinic acetylcholine receptor subunit mRNA expression.
AB  - Nicotinic acetylcholine receptor (nAChR) subunit mRNA expression in the rat
      substantia nigra (SN) was assayed by semiquantitative RT-PCR following 6
      hydroxydopamine (6-OHDA) lesion of nigrostriatal dopaminergic neurons. Six months
      after unilateral injection of 6-OHDA or saline into the SN, total RNA was
      isolated from ipsilateral and contralateral tissue samples. RT-PCR amplifications
      were performed with template titration using primers specific for sequences
      encoding 1. nAChR alpha 2-alpha 7 and beta 2-beta 4 subunits 2. Glutamic acid
      decarboxylase 3. Glyceraldehyde 3-phosphate dehydrogenase for normalization of
      template mass. PCR products specific for alpha 3, alpha 4, alpha 5, alpha 6,
      alpha 7, beta 2, beta 3, and glutamic acid decarboxylase were detected in the
      reactions containing SN RNA. This is the first evidence that alpha 7 may be
      expressed in the SN. alpha 2 and beta 4 PCR products were not detected in SN
      reactions, although they were observed in hippocampus and thalamus control
      reactions. A comparison of ipsilateral and contralateral SN RT-PCR reaction
      products showed substantial decreases in alpha 5, alpha 6, and beta 3 product
      yields following 6-OHDA, but not sham treatment. Neither the SN of sham-lesioned
      rats nor the thalamus of 6-OHDA-lesioned rats yielded similar results, indicating
      that the effects observed in 6-OHDA-treated SN were not caused by local
      mechanical damage or a nonspecific response, respectively. Effects of 6-OHDA
      treatment on alpha 3, alpha 4, alpha 7, beta 2, or glutamic acid decarboxylase
      product yields from SN samples were small or undetectable. The results suggest
      that alpha 5, alpha 6, and beta 3 subunit-encoding mRNAs are expressed at
      substantially higher levels in dopaminergic than in nondopaminergic cell bodies
      in the SN.

PMID- 9770647
TI  - Identification of L-type calcium channels associated with kappa opioid receptors
      in human placenta.
AB  - Transduction pathways of kappa receptor activation are not fully understood.
      Human placenta at term expresses only this type of opioid receptors and therefore
      offers a unique advantage for such investigations. It has previously been
      postulated that kappa receptors-mediated modulation of acetylcholine and
      placental lactogen release from human placentas require the influx of
      extracellular calcium and into the cells, possibly via voltage-dependent
      channels. We report here that another opioid-regulated placental function, the
      release of human chorionic gonadotropin (hCG), depends on extracellular calcium
      and the modality of its influx via L-type channels. Data presented demonstrated
      that the stimulation of hCG secretion by the kappa-selective agonist U69,593 was
      abolished in presence of either EGTA or the calcium channel blocker nifedipine.
      Results obtained on the combined effect of opioids and dihydropyridines indicated
      that placental kappa opioid receptors could be directly coupled to L-type calcium
      channels. The identification of the latter in villus membrane preparations,
      reported here for the first time, further contributes to the hypothesis that, in
      human placenta, kappa receptors-linked transduction mechanisms involve calcium
      and its conductance across villus membranes.

PMID- 9770648
TI  - DNA binding properties of minor groove binders and their influence on the
      topoisomerase II cleavage reaction.
AB  - We present titrations of the human delta beta-globin gene region with DNA minor
      groove binders netropsin, bisnetropsin, distamycin, chromomycin and four bis
      quaternary ammonium compounds in the presence of calf thymus topoisomerase II and
      DNase I. With increasing ligand concentration, stimulation and inhibition of
      enzyme activity were detected and quantitatively evaluated. Additionally we show
      a second type of stimulation, the appearance of strong new topoisomerase II
      cleavage sites at high ligand concentrations. The specific binding sites of the
      minor groove binders of the DNA sequence and their microscopic binding constants
      were determined from DNase I footprints. A binding mechanism for minor groove
      binders is proposed in order to explain these results especially when ligand
      concentration is increased.

PMID- 9770649
TI  - NMR study and comparison of the antigenic properties of a peptide recognized by
      two HIV-1 neutralizing antibodies.
AB  - Fab-peptide complexes formed between a 15 residue peptide derived from the HIV-1
      gp120 V3 loop and two of its cognate monoclonal antibodies, 5023A and 5025A, were
      studied using isotope-edited solution nuclear magnetic resonance (NMR)
      techniques. Since these antibodies neutralize HIV-1 virus with different strain
      specificities, this study was conducted to better understand the nature of these
      differences. The amide proton and nitrogen NMR resonances of specific residues
      were used to monitor the backbone of this peptide in these complexes. Three
      central residues of this peptide ('RAF') were found to be strongly affected by
      binding to both antibodies. Several other peptide residues were affected by
      binding to antibody 5023A but not 5025A. The antibody epitopes mapped by NMR are
      similar to those obtained previously via PEPSCAN at higher pH. One main
      difference between the PEPSCAN and NMR determined epitopes for 5023A involved two
      glycine residues of the peptide. By NMR, one of these glycines was more
      dramatically affected by antibody binding than predicted by PEPSCAN, while the
      other was much less so.

PMID- 9770650
TI  - Concerning the separation of mammalian cells in immobilized metal ion affinity
      partitioning systems: a matter of selectivity.
AB  - The effect of introducing an immobilized metal ion ligand in the lower phase of
      the PEG/Dextran system was studied on the erythrocytes and lymphocytes partition.
      The ligand in the lower phase was added as an insoluble form [Sepharose-IDA
      M(II)] with or without a ligand in the upper phase. We first checked that the
      addition of the insoluble ligand in the system did not affect the phase volume
      and settling, and also that Sepharose-IDA-M(II) partitioned strictly in the lower
      phase. Then we studied the partition of cells with various concentrations of
      ligand in the lower and upper phases. We clearly demonstrate here that the
      partition in immobilized metal ion affinity partitioning (IMAP) systems is
      correlated with the affinity between the cell surface and the ligand. Cells are
      attracted to the ligand-containing phase. This fact is important not only for the
      greater understanding of IMAP, but could also for the separation of some types of
      cells.

PMID- 9770651
TI  - Molecular recognition of a peptide mimic of the Lewis Y antigen by an anti-Lewis
      Y antibody.
AB  - Peptides as mimics of carbohydrates display a distinct advantage in vaccine
      design because of ease of synthesis and their inherent T cell-dependent nature as
      immunogens. While peptides that mimic carbohydrates have been described, it is
      not clear how they do so. To further our insight into structural relationships
      between peptide-mimics and carbohydrate structures, we have analyzed a potential
      recognition scheme between the murine monoclonal antibody, B3, directed against
      the tumor-associated antigen Lewis Y oligosaccharide and a peptide identified
      from phage display screening with B3. The Lewis Y core antigen is a difucosylated
      structure consisting of four hexose units. The B3 antibody binds to the peptide
      sequence APWLYGPA in which the putative sequence APWLY is critical for binding to
      the antibody. Not having experimental structural information for B3, the crystal
      structure of another anti-Lewis Y antibody, BR96, solved in complex with a
      nonoate methyl ester Lewis Y tetrasaccharide, provides a molecular basis for LeY
      antigen recognition and specificity, and how this binding relates to peptide
      binding. As a guide to place the APWLY motif in the B3 combining site, a fragment
      library was searched for analogous compounds that have the potential to bind to
      B3. Our modeling study shows that the B3-peptide complex shares similar
      recognition features for the difucosylated type 2 lactoseries' structure. This
      analysis provides a molecular perspective for peptide mimicry of a carbohydrate
      epitope.

PMID- 9770652
TI  - Molecular docking of superantigens with class II major histocompatibility complex
      proteins.
AB  - The molecular recognition of two superantigens with class II major
      histocompatibility complex molecules was simulated by using protein-protein
      docking. Superantigens studied were staphylococcal enterotoxin B (SEB) and toxic
      shock syndrome toxin-1 (TSST-1) in their crystallographic assemblies with HLA
      DR1. Rigid-body docking was performed sampling configurational space of the
      interfacial surfaces by employing a strategy of partitioning the contact regions
      on HLA-DR1 into separate molecular recognition units. Scoring of docked
      conformations was based on an electrostatic continuum model evaluated with the
      finite-difference Poisson-Boltzmann method. Estimates of nonpolar contributions
      were derived from the buried molecular surface areas. We found for both
      superantigens that docking the HLA-DR1 surface complementary with the SEB and
      TSST-1 contact regions containing a homologous hydrophobic surface loop provided
      sufficient recognition for the reconstitution of native-like conformers
      exhibiting the highest-scoring free energies. For the SEB complex, the
      calculations were successful in reproducing the total association free energy. A
      comparison of the free-energy determinants of the conserved hydrophobic contact
      residue indicates functional similarity between the two proteins for this
      interface. Though both superantigens share a common global association mode,
      differences in binding topology distinguish the conformational specificities
      underlying recognition.

PMID- 9770654
TI  - Head-only rotational testing in the elderly.
AB  - Head-only rotational testing (HORT) is a noninvasive technique to assess the
      vestibuloocular reflex (VOR) that can be performed in a nonlaboratory environment
      with inexpensive, portable equipment. Little data are available regarding the
      applicability of this technique to the elderly in whom limitations of cervical
      range of motion might reduce the usefulness of the technique. This study was
      designed to apply HORT to a small group of normal elderly subjects to determine
      whether the technique could be used successfully in this population. Also, the
      VOR parameters derived from HORT were compared with the results obtained from a
      group of healthy young control subjects. HORT was performed both with and without
      visual fixation of an earth-fixed target, using both active head movement and
      passive head movement. Results indicated that the responses of the elderly were
      indistinguishable from those of the young except for a slightly higher gain at 1
      Hz in the young subjects. Other findings, consistent across young and elderly,
      were that visual fixation increased gain and decreased phase lead at lower
      frequencies and that VOR parameters were unaffected by volition, that is, active
      and passive head rotation produced similar responses. These findings suggest that
      HORT can be applied to the elderly without difficulty. Future studies will assess
      the usefulness of HORT in elderly patients with VOR disorders.

PMID- 9770653
TI  - The effect of head-to-trunk position on the direction of arm movements before,
      during, and after space flight.
AB  - This contribution deals with the examination of the consequences of different
      head-to-trunk positions on arm movements under normal gravity and during
      prolonged space flight. One of the objectives of this study was to investigate
      the influence of weightlessness on the condition of the spatial analysis system.
      Aimed arm movements in the horizontal plane (pointings towards two visual
      targets) were recorded, first with eyes open, head straight (learning part), then
      with eyes closed, head straight and during yaw or roll position of the head
      (performance part). Measurements related to these different head-to-trunk
      positions were taken in one short-term and nine long-term cosmonauts preflight,
      inflight, and postflight. Terrestrial control experiments were carried out with
      an extended experimental design in 14 healthy volunteers. The analysis of these
      experiments revealed that, with eyes closed and the head in yaw position,
      cosmonauts before flight and control subjects exhibit significant slants of the
      movement plane of the arm. Contrary to terrestrial measurements, in space
      experiments roll tilt of the head to the right is correlated with considerable
      counterclockwise slant of the movement plane. This slant of the movement plane of
      the arm was interpreted as tilt of the internal representation of the horizontal
      coordinate. The effect is larger with greater distortion induced by the changed
      head position and with larger muscular involvement to keep this position. This
      effect is also increased by the reduction of information (for example, in
      microgravity). The amount and the direction of the horizontal offset of the arm
      movements are shown to be dependent on the head-to-trunk position, too.
      Additionally, we have found changes in the amplitude and in the duration of the
      arm movement, in the vertical offset, and in the curvature of the movement paths,
      depending on the experimental conditions.

PMID- 9770655
TI  - A versatile stereoscopic visual display system for vestibular and oculomotor
      research.
AB  - Testing of the vestibular system requires a vestibular stimulus (motion) and/or a
      visual stimulus. We have developed a versatile, low cost, stereoscopic visual
      display system, using "virtual reality" (VR) technology. The display system can
      produce images for each eye that correspond to targets at any virtual distance
      relative to the subject, and so require the appropriate ocular vergence. We
      elicited smooth pursuit, "stare" optokinetic nystagmus (OKN) and after-nystagmus
      (OKAN), vergence for targets at various distances, and short-term adaptation of
      the vestibulo-ocular reflex (VOR), using both conventional methods and the
      stereoscopic display. Pursuit, OKN, and OKAN were comparable with both methods.
      When used with a vestibular stimulus, VR induced appropriate adaptive changes of
      the phase and gain of the angular VOR. In addition, using the VR display system
      and a human linear acceleration sled, we adapted the phase of the linear VOR. The
      VR-based stimulus system not only offers an alternative to more cumbersome means
      of stimulating the visual system in vestibular experiments, it also can produce
      visual stimuli that would otherwise be impractical or impossible. Our techniques
      provide images without the latencies encountered in most VR systems. Its inherent
      versatility allows it to be useful in several different types of experiments, and
      because it is software driven it can be quickly adapted to provide a new
      stimulus. These two factors allow VR to provide considerable savings in time and
      money, as well as flexibility in developing experimental paradigms.

PMID- 9770656
TI  - Effects of varying acceleration of platform translation and toes-up rotations on
      the pattern and magnitude of balance reactions in humans.
AB  - Different movement synergies used to restore balance in response to sudden
      support surface displacements have been described, which include the ankle
      movement synergy and a number of multisegmental movement synergies. The purpose
      of this study was to extend the analysis of the effects of stimulus magnitude on
      the pattern and scaling of balance reactions to larger magnitudes of balance
      disturbances, and to other types of balance disturbances, in particular, forward
      translations (FT), backward translations (BT), and toes-up rotations (RT). In
      addition, we examined whether the timing and magnitude of center of body mass
      (CM) displacement is an invariant feature of corrective responses to varying
      magnitudes of balance disturbances. Thirteen healthy adults were subjected to FT,
      BT, and RT of varying acceleration/velocity. The balance disturbance induced by
      FT and BT was fundamentally different from that induced by RT. The balance
      requirement during FT and BT was to rapidly translate the CM forward/backward to
      the new position within the displaced base of support. For RT, the requirement
      was to minimize the backward displacement of the CM. As evidenced from the
      initial phase of ankle, knee, and hip angular displacements and anterior
      posterior (A-P) center of foot pressure displacement, the magnitude of the
      balance disturbance increased with increasing platform acceleration/velocity. For
      FT and BT, the present findings are consistent with the view that trajectory of
      CM is a control variable, as the timing, peak magnitude, and time to peak CM
      displacement did not vary as a function of platform acceleration/velocity.
      However, for RT, the peak magnitude and time to peak CM displacement did increase
      with increasing platform acceleration/velocity. The results demonstrate that in
      response to FT, BT, and RT, stability was restored by distinct multisegmental
      movement synergies. The corrective response to FT consisted of early knee flexion
      then ankle dorsiflexion and hip extension. The corrective response to BT
      consisted of hip flexion and ankle plantar flexion. For RT early hip flexion and
      knee flexion was observed. All muscles recorded (tibialis anterior, soleus,
      gastrocnemius, hamstrings, and quadriceps) were activated within a range of 60 to
      170 ms from onset of platform displacement. For FT, BT, and RT, the pattern and
      timing of angular displacements and muscle responses did not vary as a function
      of platform acceleration/velocity, while there was a significant effect of
      platform acceleration/velocity on the magnitude of the corrective response, that
      is, peak magnitude of corrective hip, knee, and ankle angular displacements and
      magnitude of muscle responses. The present findings indicate that multiple
      sources of spatial information are necessary for the selection and initiation of
      the appropriate corrective response to meet the requirements of the different
      balance tasks. The present results strongly endorse the concept of a postural
      control network for recovery of standing balance, as opposed to positive feedback
      through local segmental or long loop reflex circuits.

PMID- 9770657
TI  - Analyses of ribosome distribution during in vitro translation.

PMID- 9770658
TI  - Allele-specific priming in the mapping of rRNA.

PMID- 9770659
TI  - Permeabilized mammalian cells as a system for protein synthesis.

PMID- 9770660
TI  - The measurement of processivity errors in protein synthesis.

PMID- 9770662
TI  - The analysis of translational activity using a reporter gene constructed from
      repeats of an antibody-binding domain from protein A.

PMID- 9770661
TI  - A biosynthetic approach for the incorporation of unnatural amino acids into
      proteins.

PMID- 9770663
TI  - In vitro engineering using acyl-derivatized tRNAs.

PMID- 9770664
TI  - In vitro engineering using synthetic tRNAs with altered anticodons including four
      nucleotide anticodons.

PMID- 9770665
TI  - Analysis of rRNA function using specialized ribosomes.

PMID- 9770666
TI  - Determination of the peptide elongation rate in vivo.

PMID- 9770667
TI  - The measurement of missense errors during in vivo protein synthesis.

PMID- 9770668
TI  - Heelprinting analysis of in vivo ribosome pause sites.

PMID- 9770669
TI  - Analysis of eIF-2 alpha kinases in yeast.

PMID- 9770670
TI  - Continuous-flow cell-free translation, transcription-translation, and replication
      translation systems.

PMID- 9770671
TI  - Analysis of translational activity of extracts derived from oocytes and eggs of
      Xenopus laevis.

PMID- 9770672
TI  - A fractionated reticulocyte lysate system for studies on protein synthesis
      initiation factors.

PMID- 9770673
TI  - Measurement of ribosomal accuracy and proofreading in E. coli burst systems.

PMID- 9770674
TI  - Measurement of rate of protein synthesis in vitro. Preparation of Escherichia
      coli burst systems.

PMID- 9770675
TI  - In vivo mutational analysis of ribosomal RNA in Saccharomyces cerevisiae.

PMID- 9770676
TI  - Genetic selection of rRNA mutations.

PMID- 9770677
TI  - Toeprinting assays. Mapping by blocks to reverse transcriptase primer extension.

PMID- 9770678
TI  - Mapping of pseudouridine residues in RNA to nucleotide resolution.

PMID- 9770679
TI  - Chemical and enzymatic probing of antibiotic-ribosome complexes.

PMID- 9770680
TI  - Protein engineering with nonstandard amino acids.

PMID- 9770681
TI  - Internal ribosome entry sites tests with circular mRNAs.

PMID- 9770682
TI  - Gel retardation and UV-crosslinking assays to detect specific RNA-protein
      interactions in the 5' or 3' UTRs of translationally regulated mRNAs.

PMID- 9770683
TI  - Translational control by repressor proteins binding to the 5'UTR of mRNAs.

PMID- 9770684
TI  - Identification and analysis of frameshift sites.

PMID- 9770685
TI  - Synthesis and site-specific binding of thioated tRNAs to probe ribosome-tRNA
      interactions.

PMID- 9770686
TI  - [Analysis of risk factors in age-related cerebral ischemia].
AB  - The assessment is presented of 160 patients with ischaemic stroke from the point
      of view of gender, selected risk factors, incidence of internal carotid
      thrombosis (ICT) and age. The material was divided into three age groups: up to
      49 years, 50-69 years and 70 years and above. A significant prevalence of men was
      noted in both younger age groups. With progressing age atrial fibrillation was
      found significantly more frequently while the number of patients with ICT was
      decreasing. Similarly, the number of smokers and patients with raised hematocrit
      value was decreasing. The most frequent risk factor for ischaemic was
      hypertension. Obesity and diabetes were not significantly changing in relation to
      age in their prevalence in this material.

PMID- 9770687
TI  - [Acute phase proteins: alpha-1-acid glycoprotein (AGP) and alpha-1
      antichymotrypsin (ACT) in serum of patients with cerebral ischemic stroke].
AB  - The purpose of this study was to investigate the dynamics of selected acute phase
      proteins in serum of patients with cerebral ischaemic stroke. The investigation
      was done in 30 patients with cerebral ischaemic stroke. Alpha1-acid glycoprotein
      and alpha-1-antichymotrypsin levels in serum of patients with cerebral ischaemic
      stroke on III and VII day of illness were statistically significantly higher than
      in the control group.

PMID- 9770688
TI  - [The assessment of flow velocity in carotid and intracranial arteries in three
      different age groups].
AB  - In this report we assess the systolic maximal flow velocity in carotid and
      intracranial arteries in 191 subjects with no history of cerebral vascular
      disease in 3 age groups: 20-40 years (1 group), 41-60 years (2 group), and above
      60 years (3 group). The subjects were assessed using Sonomed Transcranial Doppler
      Spectrograph according to generally accepted principles. The purpose of the study
      was to establish the mean value of maximal flow velocity in each particular
      artery in three age groups, and to observe the changes in this parameter with
      age. The results were analyzed using statistical methods and a significant
      decrease in blood flow, Vmax, was found in all investigated arteries. A mean
      decrease of 8.02% in flow velocity Vmax was found, when comparing groups 2 and 1,
      and difference 15.99% comparing 3 and 1.

PMID- 9770689
TI  - [Non-smoking as risk factor for Alzheimer's disease?].
AB  - In several case-control studies an inverse association between smoking and
      Alzheimer's disease (AD) has been observed. The purpose of this study was to
      assess the hypothesis that nonsmoking may be a risk factor for AD. A case-control
      study was conducted on 88 patients with the clinical diagnosis of "probable" AD
      and 54 controls matched for age and sex. Patients and controls were compared for
      number of cigarette smokers versus nonsmokers and for male to female ratio as
      well. In the group of patients onset of AD, duration of illness and decline of
      mental function documented by GDS scale was estimated in smokers in comparison
      with nonsmokers. Among the variables studied statistical significance reached
      predominance female to male in nonsmokers only. As female predominance is also
      observed in patients with AD, the significance of nonsmoking as a risk factor for
      AD has to be treated carefully.

PMID- 9770690
TI  - [Lyme disease in children].
AB  - In the recent years the number of diagnosed cases of Lyme Disease has tended to
      increase. This is due to the possibility of serological examinations. Between
      1992-95 at the Neurological Department of 2nd Chair of Pediatrics Silesian
      Medical Academy in Katowice 7 children with Lyme Disease were hospitalized. The
      authors analysed the clinical course, important laboratory and serological data
      and treatment effects.

PMID- 9770691
TI  - [Diagnostic value of tumor necrosis factor-alpha (TNF-alpha) determination in
      cerebrospinal fluid (CSF) in the course of neural infections].
AB  - In the central nervous system (CNS) infections a substantial role play
      inflammatory cytokines, especially TNF-alpha. They are implicated to initiate the
      local response leading to cerebral damage during meningitis. The purpose of this
      study was estimation of the diagnostic value of determining TNF-alpha
      concentrations in the CSF in the course of neuroinfections. Analyses were
      performed in 15 patients with purulent, bacterial meningitis (group A) and in 15
      patients with lymphocytic meningitis (group B). CSF's concentrations of TNF-alpha
      were measured by the ELISA method (Genzyme Diagnostic, Cambridge, USA), on the
      day of admission and on the fourteenth day of treatment. In group A mean TNF
      alpha concentration in CSF on admission was 285.73 pg/ml and in group B 4.07
      pg/ml. On the fourteenth day of treatment mean TNF-alpha concentrations were 1.14
      pg/ml and 0 pg/ml, respectively. The highest CSF TNF-alpha levels were observed
      in the most severely ill patients (group A). In several cases in this group there
      were positive correlations between TNF-alpha concentration and CSF white blood
      cell counts and protein concentration. Correlation of high levels of TNF-alpha
      with the severity of clinical course was observed in group B as well. Examination
      of CSF for TNF-alpha concentration could be useful in the differential diagnosis
      of CNS inflammations. TNF-alpha concentrations in CSF correlate with the severity
      of clinical course of meningitis and could have a prognostic value.

PMID- 9770692
TI  - [Influence of NMDA receptor stimulation in brain cortex and hippocampus on NO
      dependent cGMP synthase. Effect of ischemia on NO related biochemical processes
      during recirculation].
AB  - Stimulation of NMDA receptor increases NO-dependent cGMP synthesis. A
      significantly higher cGMP level was observed in hippocampus (about 8-fold
      increase) than in cerebral cortex (2.5-fold increase), as compared to basal
      value. The activity of NO synthase (NOS) and the basal level of cGMP in
      unstimulated slices were only slightly higher in hippocampus than in the cortex.
      About 60% of NOS total activity was found in the brain membrane fraction. The
      enzyme activity was not affected by glucocorticoids, even after 20 days of
      hydrocortisone treatment in dose of 40 mg/kg b.w. Brain ischemia induced by
      ligation of the both common carotid arteries in gerbils (Meriones unquiculatus)
      significantly increased NOS activity as well as cGMP and putrescine
      concentrations but decreased mono-ADP-ribosolation of proteins. Changes of NOS
      activity and cGMP concentration evoked by ischemia were decreased by specific
      inhibitor of the neuronal form of NOS (nNOS), 7-nitrodazole and the inhibitor of
      guanylate cyclase, LY 83,583 administered respectively in a dose of 25 mg/kg b.w.
      and 6 mg/kg b.w. 5 min. before ischemia. The inhibitor of nNOS, 7NI, did not
      change the concentration of putrescine during ischemia and reperfusion. Our
      results indicated that these inhibitors could protect the brain against excessive
      production of nitric oxide and biochemical processes dependent on it. In this way
      they may offer a new strategy in the therapy of brain ischemia.

PMID- 9770693
TI  - [The use of pedicle periosteal flap in plastic surgery of anterior skull base].
AB  - In 12 cases of large traumatic defects of the anterior skull base plastic surgery
      was performed using large periostial flap to separate the nasopharynx from the
      extradural area. After a large biauricular scalp flap was formed, precise
      preparation of periostial flap was done. The bifronto-transfrontal sinus or
      transfrontal sinus approach was performed. Next cranialization of the frontal
      sinus was done and then it was filled with muscle. Afterwards the floor of the
      frontal sinus and skull base with defect were covered with periostial flap
      pedicled along supraorbital ridge. Finally irradiated homograft of dura or fascia
      lata was glued intradurally onto the place of the dural defect. In all of the
      patients CSF-rhinorrhea stopped immediately after surgery. Among patients
      observed from 2 to 4 years after surgery neither recurrent rhinorrhea nor
      infection appeared.

PMID- 9770694
TI  - [Conservative treatment of cerebral arteriovenous malformations. Follow-up study
      of 31 cases].
AB  - The clinical course of 31 patients with conservatively treated intracranial
      arteriovenous malformations (AVM's) was followed-up. The average follow-up period
      was 8.2 years, 75% of patients were followed up for more than 5 years. The
      initial symptom was intracranial bleeding in 21 patients (68%), seizure in 5
      (16%), neurological deficit in 2 (6.5%), headache in 2 (6.5%) and intracranial
      hypertension in 1 (3%). The prognosis was more favourable for patients presenting
      with seizures than for patients presenting with haemorrhage. Patients in the
      haemorrhage group had 29% incidence of haemorrhage causing 14% mortality in this
      group. Of the 31 patient's 20 (64.5%) had a good clinical outcome, 4 (13%) had a
      fair outcome and 2 (6.5%) poor, 5 patients died, with one not due to AVM. There
      was no correlation between pregnancy and bleeding.

PMID- 9770695
TI  - [Large intracranial tumors invading skull base].
AB  - Large intracranial tumours (diameter > 4.5 cm) invading skull base are not
      frequent. In Department of Neurosurgery in Poznan 22 patients were operated on
      between 1977-1966. There were 15 males and 7 females. Mean age was 34.78 +/-
      15.31 years. The authors analyse the time between the onset of illness and
      diagnosis, symptoms and neurological condition. Tumour localization was verified
      by X-rays, computed tomography, cerebral angiography and in some cases magnetic
      resonance. There were 11 tumours in both fossae--anterior and middle, in 7 tumour
      site was limited to anterior and in 4--to middle fossa. Extracranial tumour
      penetration was observed as follows: in 10 cases into paranasal sinuses, 10-
      orbit, 8--nasopharyngeal cavity and in 4 cases into subtemporal fossa. The
      authors discuss surgical methods, histological appearances and postoperative
      complications. Mortality rate was 9% (2 patients died).

PMID- 9770696
TI  - [Colloid cysts of the third ventricle].
AB  - Colloid cysts of the 3rd ventricle, diagnosis and treatment. 11 patients with
      colloid cyst of the 3rd ventricle were diagnosed and treated at the Department of
      Neurosurgery the Medical University of Warsaw, between 1987 and 1996. The
      patients comprised 5 females and 6 males, aged 22 to 58 years. Mean time from the
      occurrence of the first symptoms to surgery was 23 months, although this varied
      in individual cases from 8 days to 10 years. In the majority of patients, the
      leading symptoms were: headaches, nausea, vomiting and papilloedema, comprising
      symptoms of high intracranial pressure. Slowly progressing symptoms of organic
      brain damage syndrome were observed in 5 patients. Preoperative diagnosis was
      based on CT of the head in 8 patients, on NMR in 2 and on both CT and NMR in 1
      patient. At the first stage of treatment, a ventriculo- peritoneal Y-shunt was
      used in 3 patients to eliminate symptoms of high intracranial pressure. All
      patients then underwent radical surgery. 9 patients were treated by craniotomy in
      the frontal region with incision of the cortex and then through the lateral
      ventricle and interventricular foramen. 1 patient was operated by craniotomy and
      through the terminal lamina of the 3rd ventricle. In 1 case the cyst was
      evacuated via neuroendoscope. There were no cases of mortality among our
      patients. Full recovery occurred in 8 patients. In 3 patients symptoms of organic
      brain damage syndrome observed prior to surgery remained, but in a lesser degree,
      which may be a result of the correct diagnosis being established too late. In
      over 5 years' follow-up, no cases of recurrence were observed.

PMID- 9770697
TI  - [Post-stroke epilepsy].
AB  - The frequency of cerebrovascular aetiology of epilepsy is estimated at 3-30%, and
      the rate is significantly higher in studies carried out in developed world. Early
      seizures, variously defined by different authors (usually as those occurring
      within first week or first two weeks after stroke) occur in 2.5-6% of patients,
      in most of them within the first 24 hours after stroke. Early seizures constitute
      a major risk factor of poststroke epilepsy, but in many patients seizures do not
      recur after acute phase of stroke. The pathophysiology of poststroke seizures is
      not fully elucidated, probably it is different for early and late seizures.
      Several investigations evaluated the connection between seizures and localization
      of vascular foci, the results are not consistent; most investigators believe that
      seizures occur more frequently in cases of cortical localization of the focus.
      Seizures are more common in haemorrhagic than in ischaemic strokes. The most
      common type of seizures are simple partial seizures, the rarest are complex
      partial seizures. The prognostic value of EEG is of little importance:
      nevertheless, in poststroke patients who had at least one seizure, diffuse
      slowing of background activity or PLED are associated with increased risk of
      seizure recurrence. Early seizures do not require long-term antiepileptic
      treatment; late seizures usually well respond to treatment.

PMID- 9770698
TI  - [Comprehensive rehabilitation of multiple sclerosis patients].
AB  - Rehabilitation of Multiple Sclerosis patients is one of the most specific
      problems because of its variable and unforeseeable course. Rehabilitation
      procedures of those patients must be performed individually and very elastic in
      every case. In this elaboration the most commonly appeared forms and course of MS
      have been presented. According to it the planing of the rehabilitation has been
      adapted. Basic rules of the exercises during the relapse and during the remission
      have been presented. The greatest attention has been paid to the problems of
      managing spasticity and the reeducation of neurogenic bladder.

PMID- 9770699
TI  - [The central nervous system and the lymphatic system. Lymphatic drainage of the
      cerebrospinal fluid].
AB  - The authors have presented the less known CSF alternative pathways. Besides the
      CSF absorption into blood vessels in arachnoidal villi alongside venous sinuses
      there is additional CSF outflow to the lymphatic vessels. For many years the
      neurophysiologists did not take into account and did not appreciate this route
      despite it had been in XIX-th century. In those times Schwalbe noticed that after
      Berlin blue injection into the cranial subarachnoid space of exsanguinated
      rabbits and dogs the markers uptake increased in the local cervical lymphatic
      nodes. The review contains a structural description as well as a physiological
      explanation of the alternative CSF outflow. The paper also shows the development
      of views or: this topic. The prelymphatic cerebral vessels described by Gasley
      Smith and perineural lymphatic pathways around cranial and spinal nerves seem to
      be the most significant ones connecting the central nervous system and the
      lymphatic system. It has been proved during animal experiments, that 20-30% CSF
      flows through the alternative pathways. It is too early, to come to the final
      conclusions. But the present results concerning CSF outflow to the lymphatic
      system can confirm its influence on the CNS immunology, hydrocephalus and
      pseudotumour cerebri aetiology and olfactory sensation (the flow of the fluid
      might help to remove the odor-stimulating molecules).

PMID- 9770700
TI  - [The usefulness of neurological and radiological signs in lumbar discopathy].
AB  - The aim of the work was to show the usefulness of neurological and radiological
      signs in the patients with L4 and L5 discopathy. The axial symptoms with the
      highest occurrence frequency and the differential symptoms closely connected with
      definite disc pathology: the type and/or the level of discopathy were defined.
      The problem of importance of the above-mentioned signs in the diagnostic
      management was discussed on the basis of literature. The significance of
      bilateral and polyradicular symptoms in the diagnosis of central lumbar disc and
      unilateral symptoms in the diagnosis of lateral lumbar disc were emphasized.

PMID- 9770701
TI  - [Head injuries in pediatric age].
AB  - Head trauma is the leading cause of morbidity and death in paediatric population.
      The authors present an outline of contemporary knowledge on the paediatric head
      injury on the ground of literature and own experience. The value of Glasgow Coma
      Scale, its modifications and other prognostic factors in children's population
      after head trauma is discussed. The management of mild head injury is also
      disputed. In conclusion it is stressed that since many differences in
      epidemiology, mechanism, pathophysiology and outcome of head injury in childhood
      and adults exist the separation of "paediatric neurotraumatology" is reasonable.

PMID- 9770702
TI  - [A case of asymptomatic central pontine myelinolysis].
AB  - In 1959 year Adams, Victor and Mancella described central pontine myelinolysis
      (CPM) as a disease of fulminant course and fatal prognosis. In the typical cases
      progressive tetraparesis with bulbar signs results in severe crippledom or death.
      The disease was diagnosed before only by autopsy, as soon as the modern
      radiological technics i.e., CT and MRI were developed it is sometimes
      successfully diagnosed with patients alive. The authors present the case of 62
      year old woman suffering from slight hemiparesis which made use to perform the CT
      examination. It showed central pontine lesion which was confirmed by MRI
      examination. The authors suggest that there are not only typical cases of CPM but
      also the asymptomatic ones as presented above.

PMID- 9770703
TI  - [Migraine and associated epileptic seizures].

PMID- 9770704
TI  - [Difficulties in diagnosis and therapy in a case of brain inflammatory process in
      patient with Hodgkin's disease].
AB  - A rare case of cerebral probable viral inflammatory process in a patient with the
      Hodgkin's disease has been presented. The diagnosis of the neurological disorder
      was based on the clinical course of the disease, the dynamics of the process
      observed in CT and MRI examinations. The pathogen was not identified in
      bacteriological and viral tests. Hodgkin's disease restricted to the spleen was
      diagnosed in postmortem examination. The presented case demonstrates variability
      of the clinical picture and difficulties in diagnosing viral encephalitis.

PMID- 9770705
TI  - [Treatment of iliac vein thrombosis by use of filter placed in the inferior cava
      vein in a female patient after reoperation of meningioma of the smaller section
      of the sphenoid bone].
AB  - Deep phlebothrombosis is a one of the postoperative complications in neurosurgery
      in 90% localized in lower extremities. The brain contains the highest
      concentration of tissue thromboplastin compared with the other organs. That fact
      plays an important roll in pathophysiology of thrombo-embolic process in
      neurosurgery. The most frequent places of thrombogenesis are venous sinus of
      soleus muscle and gastrocnemius muscle, next: deep veins of crus, femoral veins
      and iliac veins. We describe the case of the efficient treatment of femoral vein
      and iliac vein thrombosis using filter placed under control of monitor in the
      inferior caval vein higher than the thrombus.

PMID- 9770706
TI  - [Epidural gas aggregation in the course of gaseous degeneration of lumbar
      intervertebral disk as a cause of foot paresis].
AB  - The finding of gas within the vertebral disc space ("vacuum phenomenon") is
      relatively common. Degenerative spine disease, gaseous degeneration of the
      intervertebral disc, and epidural gas were disclosed on imaging study. The
      epidural gas could be attributed to gaseous disc degeneration. The nerve root in
      presented patient was compressed by epidural gas. Following surgery the clinical
      syndrome including foot drop has thoroughly resolved.

PMID- 9770707
TI  - [The application of intervertebral implant for spine stabilization].
AB  - The purpose of this study is determination of efficacy of the SOCON posterior
      device combined with PROSPACE PLIF interbody fusion system in the treatment of
      lumbar spondylolisthesis. Both devices are fabricated by Aesculap AG. Lumbar
      interbody fusion is a surgical technique used to create local spinal stability.
      Recently there is a wide group of interbody implants made of different
      osteoconductive materials. The authors present brief classification of lumbar
      interbody fusion implants. The 1 case of spondylolisthesis L5/S1 is analyzed
      including operative technique and outcome. CONCLUSION: PROSPACE is effective as
      interbody support and fusion element.

PMID- 9770708
TI  - [Report from the 4th International Symposium on Neurotraumatology, August 22-28,
      1997, Seoul, South Korea].

PMID- 9770709
TI  - [Report from the 14th Annual Meeting of Pediatric Neurosurgery in Poznan, March
      2, 1998 on "The covering of the brain in neurosurgical practice"].

PMID- 9770710
TI  - [Report from the 3rd All-Polish Symposium on the informatics application in
      neurology and related sciences. Warsaw, October 10, 1997].

PMID- 9770711
TI  - [Need for quality circles for PET?].

PMID- 9770712
TI  - [First results of radioiodine therapy of multifocal and disseminated thyroid
      gland autonomy and use of a TcTUs-adapted dose concept].
AB  - AIM: The presented study examines prospectively the efficiency of a dose concept
      for radioiodine therapy (RIT) adapted to the pretherapeutic 99mTc-pertechnetate
      thyroid uptake under suppression (TcTUs) in patients with multifocal (MFA) and
      disseminated (DISA) autonomy. This concept considers the total thyroid as target
      volume and uses target doses from 150 Gy to 300 Gy according to the TcTUs, which
      is as a measure for the "autonomous volume" of the thyroid. METHODS: The data of
      75 patients (54 female, 21 male; age 71 +/- 9 years) with MFA of DISA were
      evaluated. RIT was performed on patients presenting with normal values for free
      triiodothyronine and thyroxine and endogenous suppression of the basal
      thyrotropin (TSH). The following target dose were used for a TcTUs of 1.5-2.5%
      150 Gy, for 2.51-3.5% 200 Gy, for 3.51-4.5% 250 Gy, and for > 4.5% 300 Gy. The
      radiation dose to be administered was calculated using a modified Marinelli
      formula. The therapy was considered as successful. When the basal TSH was above
      0.5 mU/l and autonomous areas had disappeared in thyroid scintigraphy or the TcTU
      was below 1.5%, respectively. The average follow-up period was 8 +/- 4 months.
      RESULTS: The success rates average to 92%. Only in one case a subsequent
      subclinical hypothyroidism and in a further case an immunogenic hyperthyroidism
      occurred. CONCLUSION: The presented data indicate that even patients with a
      marked autonomy (TcTUs > 3.5%) can thus expected to be cured by of a one time
      therapy with success rate of over 90% using the presented dose concept. The rate
      of early hypothyroidism can altogether be estimated as very low.

PMID- 9770713
TI  - [Individual calculation of the minimal effective levothyroxine dose in prolonged
      suppression tests].
AB  - AIM: A formula for calculating the minimum suppressive levothyroxine dose in
      prolonged suppression tests using body weight and TSH level is derived from a
      large number of cases. METHOD: In 1239 euthyroid patients (TSH > 0.30 mU/l) a
      suppression test with levothyroxine substitution for at least 6 weeks was
      performed. The hormone dose was primarily based on the initial TSH level using
      the empirical value TSH x 100, with a range between 50 and 150 micrograms per
      day. RESULTS: In 900 patients (73%), the TSH level was suppressed during the
      medication (TSH < 0.30 mU/l). Among them, we found 211 cases with an intermediate
      TSH suppression (TSH between 0.10 and 0.20 mU/l). Following the formula f =
      levothyroxine dose [microgram]/(body weight [kg] x initial TSH level [mU/l]) an
      average factor of 1.57 was calculated to obtain the suppressive dose in this
      group. As usually a complete TSH suppression (< 0.10 mU/l) is required, we
      recommend factor 2 for practical use. A consideration of the body weight revealed
      that 313 patients actually received a hormone dose equivalent to 2 x weight x
      TSH. In this group, a TSH suppression was found in 262 patients (84%), a
      factitial hyperthyreosis was not observed. When contemplating the three subgroups
      of this collective, who received daily doses of 50, 75 and 100 micrograms
      levothyroxine, respectively, we neither found a significant difference in the
      average body weight, nor in the value of the suppressed TSH. However, the
      correlation between the average initial TSH levels in these groups and the
      respective suppressive hormone doses clearly demonstrates their dependence on the
      thyroid regulation. CONCLUSION: The minimum suppressive levothyroxine dose does
      not only depend on the body weight, but also on the initial TSH level. It can be
      estimated using the formula 2 x body weight x initial TSH (range between 50 and
      150 micrograms per day).

PMID- 9770714
TI  - [Change of 99m technetium-pertechnetate uptake by the thyroid under suppression
      (TcTus) induced by optimization of iodine supply in Germany].
AB  - AIM: The present study deals with the change of the 99mTechnetium-pertechnetate
      thyroid uptake under suppression (TcTUs) in dependence on the urinary iodine
      excretion. METHODS: The study collective comprises 510 patients with euthyroid
      goiter (N = 91), with functional thyroid autonomy (N = 361) and with Graves,
      disease (N = 58), who were examined in the own thyroid ambulance between January
      1995 and February 1997 and who presented with endogeneous or exogeneous TSH
      suppression. All patients received a quantitative thyroid scintigraphy with
      99mTechnetium-pertechnetate and a measurement of the urinary iodine excretion.
      RESULTS: The TcTUs from the whole collective shows an inverse correlation to the
      urinary iodine excretion for the range of 0 to 500 micrograms iodine/g
      creatinine. The TcTUs remains constant on a low basal level for iodine excretion
      values over 500 micrograms iodine/g creatinine. Significant differences occur in
      dependence on the underlying disease. TcTUs is constantly low in patients with
      euthyroid goiter, independent of the iodine excretion value. The TcTUs is
      significantly increased in patients with functional thyroid autonomy or Graves'
      disease when iodine excretion is below 100 or 50 micrograms iodine/g creatinine
      respectively, but shows only minor changes when iodine excretion rises up to 500
      micrograms iodine/g creatinine. When iodine excretion exceeds 500 micrograms
      iodine/g creatinine, the TcTUs of patients with thyroid autonomy drops down to a
      low basal level. CONCLUSION: The reference range of TcTUs for assessing
      functional thyroid autonomy will not change significantly when the iodine supply
      in Germany improves. The TcTUs of patients with functional thyroid autonomy might
      be up to one third higher under conditions of iodine deficiency than in iodine
      sufficiency. This should be taken into account, when therapeutical consequences
      were derived from the TcTUs. The TcTUs cannot be interpreted for iodine excretion
      values over 500 micrograms iodine/g creatinine.

PMID- 9770716
TI  - [Simultaneous occurrence of Graves' ophthalmopathy and autonomous thyroid
      nodules].
AB  - Estimations regarding the simultaneous occurrence of Graves' ophthalmopathy and
      autonomously functioning thyroid nodules expect frequencies of 0.05-0.2%.
      Contrary to these estimated numbers, only 3 patients with these simultaneous
      manifestations were identified in an out patient thyroid clinic within a period
      of 10 years. The possible protection by the autonomous thyroid nodules against
      the manifestations of Graves' disease is discussed.

PMID- 9770715
TI  - [Chest X ray: routine indication in the follow-up of differentiated thyroid
      cancer?].
AB  - AIM: This retrospective study sought to elucidate whether routine chest x-ray is
      still useful for detection of pulmonary metastases in low risk patients despite
      the high sensitivity of the tumor marker thyroglobulin. METHOD: The hospital
      files of 609 patients with well-differentiated thyroid cancer were analysed.
      Pulmonary formation of metastases was diagnosed in 50 patients. The thyroglobulin
      value at the time of diagnosis was compared with the chest x-ray findings and, if
      present, additional diagnostic information such as Iodine-131 whole body
      scintigraphy (WBS) and thorax CT. RESULTS: The sensitivity of the chest x-ray to
      detect pulmonary metastases was at 52% lower than that of WBS (64%), thorax CT
      (82%) and thyroglobulin during suppression therapy (86%). Among the patients with
      papillary carcinoma stage I and II (UICC 1987), only 1 patient developed
      pulmonary metastases during follow up. In this low risk group of patients,
      detection of lung metastases exclusively by chest x-ray, without elevation of
      thyroglobulin level is extremely rare (calculated probability 1/4000) and
      associated with considerable costs. CONCLUSION: Routine, life long chest x-ray in
      low risk patients without a suspected recurrence (e.g. positive thyroglobulin)
      needs to be reconsidered.

PMID- 9770717
TI  - Discordance of sialography and scintigraphy in unilateral chronic sialadenitis.
AB  - A Tc-99m pertechnetate salivary gland scintigraphy, digital subtraction
      sialography (DSS) and cytological findings of a 48-year-old female who received I
      131 therapy for the treatment of follicular carcinoma of thyroid are presented.
      Post radioiodine therapy sialoscintigraphy showed increased blood flow and uptake
      with decreased secretion in the left parotid gland suggesting acute inflammation.
      In contrast, DSS and fine needle aspiration biopsy (FNAB) findings were
      consistent with chronic sialoadenitis. Follow-up scintigraphy one month later
      showed normal blood flow and decreased uptake and confirmed the diagnosis of
      chronic sialoadenitis. In right of this case, we conclude that since management
      of sialoadenitis depends on the stage of inflammation scintigraphic findings
      should be interpreted together with radiology and FNAB findings if necessary.
      When chronic sialoadenitis is followed by acute exacerbations, diagnosis based
      exclusively on sialoscintigraphic findings may result in inadequate patient
      management.

PMID- 9770718
TI  - Comparative effects of secondary bile acids, deoxycholic and lithocholic acids,
      on aberrant crypt foci growth in the postinitiation phases of colon
      carcinogenesis.
AB  - The objective of this study was to investigate the effect of deoxycholic (DCA)
      and lithocholic (LCA) acids on the postinitiation phases of colon cancer. Male
      Sprague-Dawley rats (n = 170) were injected with azoxymethane (2 injections at 15
      mg/kg body wt sc given 1 wk apart) and fed a control (CON) AIN-93 diet. Two weeks
      after the second azoxymethane injection, 10 animals were killed and aberrant
      crypt foci (ACF) were enumerated. The remaining animals were randomly assigned to
      four diet groups: 1) CON, 2) DCA, 3) LCA, and 4) high fat (HF, a positive control
      group). Bile acid diets consisted of 0.2% by weight DCA or LCA; HF diets
      consisted of 20% fat (5% soybean oil + 15% beef tallow by weight). Animals were
      killed at Weeks 3, 12, and 20 (from 1st carcinogen injection), and number and
      growth features of ACF and adenomatous lesions were enumerated in the colon. At
      Week 12, ACF number and small, medium, and large (1-3, 4-6, and > or = 7
      crypts/focus, respectively) ACF were higher in the HF group than in the DCA, LCA,
      and CON groups (p < or = 0.05). By Week 20, ACF number and small, medium, and
      large ACF were similar in the LCA and HF groups, whereas the response was similar
      in the DCA and CON groups. Average crypt multiplicity was higher in the HF and
      LCA groups than in the DCA and CON groups (p < or = 0.05). Microadenoma (MA)
      incidence was higher in the HF group than in the CON and LCA groups (p < or =
      0.05). Regional distribution patterns for ACF number were similar to MA and tumor
      distribution patterns within the CON, DCA, and HF groups. In the LCA group, ACF
      number and MA showed a proximal predominance in regional distribution, whereas
      tumors showed a distal predominance. HF diets provided the most stimulatory
      environment, immediately enhancing the number and growth of ACF and MA incidence.
      In conclusion, HF and LCA diets exerted distinct effects on postinitiation phases
      of colon cancer, whereas the DCA diet did not.

PMID- 9770719
TI  - Effects of phytoestrogens on DNA synthesis in MCF-7 cells in the presence of
      estradiol or growth factors.
AB  - Phytoestrogen effects on estrogen action and tyrosine kinase activity have been
      proposed to contribute to cancer prevention. To study these mechanisms, a number
      of phytoestrogens and related compounds were evaluated for their effects on DNA
      synthesis (estimated by thymidine incorporation analysis) in estrogen-dependent
      MCF-7 cells in the presence of estradiol (E2), tamoxifen, insulin, or epidermal
      growth factor. We observed that 1) at 0.01-10 microM, genistein and coumestrol
      enhanced E2-induced DNA synthesis, as did 10 microM enterolactone. Chrysin at 1.0
      10 microM and 10 microM luteolin or apigenin inhibited E2-induced DNA synthesis,
      as did all compounds at > 10 microM, 2) tamoxifen enhanced genistein-induced DNA
      synthesis but inhibited DNA synthesis induced by all other compounds, and 3)
      genistein enhanced insulin- and epidermal growth factor-induced DNA synthesis at
      0.1-1.0 and 0.1-10 microM, respectively. At higher concentrations, inhibition was
      observed. Similar effects were seen with coumestrol. In conclusion, the effects
      of phytoestrogens in the presence of E2 or growth factors are concentration
      dependent and variable. At low concentrations, genistein and coumestrol
      significantly enhanced E2-induced and tyrosine kinase-mediated DNA synthesis; at
      high concentrations, inhibition was observed. Differing effects were observed
      with the other compounds. The variable effects of phytoestrogens on DNA synthesis
      must be considered when their roles in cancer prevention or treatment are
      evaluated.

PMID- 9770720
TI  - Longitudinal study of body cell mass depletion and the inflammatory response in
      cancer patients.
AB  - There is recent evidence that the inflammatory response may be important in the
      disproportionate loss of body cell mass in cancer patients. To examine this
      further, 18 male patients with lung or gastrointestinal cancer were studied over
      a 12-week period. In addition to weight, anthropometry, C-reactive protein
      (marker of the inflammatory response), albumin, and total body potassium were
      measured at baseline and 12 weeks. When those patients who lost total body
      potassium were compared with those who had not, there was a significant increase
      in the baseline and 12-week C-reactive protein concentrations (p < 0.05). The
      reduction in total body potassium was also associated with a reduction in triceps
      skinfold thickness (p < 0.05). There were significant correlations between the
      mean C-reactive protein concentration and the relative (r = -0.846, p < 0.001)
      and absolute (r = -0.806, p < 0.001) change in total body potassium over the
      follow-up period. This study demonstrates the association of a chronic
      inflammatory response with the rate of loss of body cell mass observed in cancer
      patients.

PMID- 9770722
TI  - Different bile acids exhibit distinct biological effects: the tumor promoter
      deoxycholic acid induces apoptosis and the chemopreventive agent ursodeoxycholic
      acid inhibits cell proliferation.
AB  - Epidemiological studies have suggested that the concentration and composition of
      fecal bile acids are important determining factors in the etiology of colon
      cancer. However, the mechanism by which these compounds influence tumor
      development is not understood. To begin to elucidate their mechanism of action,
      four bile acids, cholic acid, chenodeoxycholic acid, deoxycholic acid (DCA), and
      ursodeoxycholic acid, were examined for their effects on the growth of several
      different tumor cell lines. We found that incubating cells with chenodeoxycholic
      acid or DCA caused morphological changes, seen by electron and light microscopy,
      that were characteristic of apoptosis, whereas incubating cells with
      ursodeoxycholic acid inhibited cell proliferation but did not induce apoptosis.
      Cholic acid had no discernible effect on cells. Notably, the apoptosis induced by
      DCA could be suppressed by inhibiting protein kinase C activity with calphostin
      C. These results indicate that different bile acids exhibit distinct biological
      activities and suggest that the cytotoxicity reported for DCA may be due to its
      capacity to induce apoptosis via a protein kinase C-dependent signaling pathway.

PMID- 9770721
TI  - Effect of ascorbic acid dose taken with a meal on nitrosoproline excretion in
      subjects ingesting nitrate and proline.
AB  - We determined the dose of ascorbic acid (ASC) given to subjects with a standard
      400-calorie meal that inhibited N-nitrosoproline (NPRO) formation when we gave
      400 mg of nitrate one hour before and 500 mg of L-proline with the standard meal.
      Volunteers consumed their normal US diets but restricted their intakes of
      nitrate, proline, NPRO, and ASC. NPRO and N-nitrososarcosine (NSAR) were
      determined in the 18-hour urines by methylation followed by gas chromatography
      thermal energy analysis. Mean NPRO yields were 10.7, 41.9, 33.2, 22.3, and 23.1
      nmol for groups of 9-25 subjects taking proline alone, proline + nitrate, and
      proline + nitrate + 120, 240, and 480 mg of ASC, respectively. There was a
      significant trend to lower NPRO yields as the ASC dose was raised. These results
      correspond to inhibitions by ASC of 28%, 62%, and 60%, respectively. Pairwise
      comparison showed that each group taking ASC formed significantly less NPRO than
      the group given only proline + nitrate. Mean NSAR yields were 9.0 nmol when
      proline alone was taken and 16.9-24.0 nmol when proline + nitrate + ASC was
      taken, with no trend to increase as the ASC dose was raised. However, NPRO and
      NSAR yields in individual urines were correlated with each other. We concluded
      that 120 mg of ASC taken with each meal (360 mg/day) would significantly reduce
      in vivo nitrosamine formation, similar to tests by Leaf and co-workers
      (Carcinogenesis 8, 791-795, 1987) in which the reactants were taken between
      meals. The inhibitory dose of ASC may be < 120 mg/meal when doses of nitrate and
      proline are not taken.

PMID- 9770723
TI  - Inhibition of skin carcinomas but not papillomas by sphingosine, N
      methylsphingosine, and N-acetylsphingosine.
AB  - The sphingoid base backbones of sphingolipids are highly bioactive compounds that
      affect cell growth, differentiation, diverse cell behaviors, and programmed cell
      death. Therefore, the efficacy of sphingosine (SPH) and the analogs N
      acetylsphingosine (NAS), N-methylsphingosine (NMS), octylamine (OCT), and
      sterylamine (STR) in the prevention of skin cancer was assessed in female Sencar
      mice by measuring effects on the induction of epidermal ornithine decarboxylase
      (ODC) activity and hyperplasia by 12-O-tetradecanoylphorbol-13-acetate (TPA) and
      effects on the induction of skin tumors by 7, 12-dimethylbenz[a]anthracene (DMBA)
      and TPA. ODC was measured in the shaved dorsal skin of mice treated topically
      with 0.05-20 mumol of these compounds 30 minutes before application of 8.5 nmol
      of TPA in 0.2 ml of acetone. ODC activity was inhibited by > or = 5 mumol of SPH
      and STR, > or = 10 mumol of NAS and NMS, and 20 mumol of OCT. In contrast, the
      induction of hyperplasia was not inhibited by application of these compounds 30
      minutes before TPA. Two carcinogenesis studies were conducted with 10 nmol of
      DMBA as the initiator and 3.2 nmol of TPA (2x/wk for 15 wk) as the promoter. In
      the first study, NAS, NMS, OCT, and STR (0.05 and 0.5 mumol) were applied before
      each TPA application. Papilloma incidence and multiplicity were not inhibited,
      but NAS (0.05 mumol) and NMS (0.05 and 0.50 mumol) increased cancer-free
      survival. In the second experiment, SPH, NAS, and NMS (0.05 and 0.5 mumol) were
      applied 30 minutes before each TPA treatment and twice weekly for 10 weeks after
      the final TPA treatment. Papilloma incidence and multiplicity were not inhibited;
      however, the proportion of mice without carcinoma was increased by both doses of
      SPH and by 0.5 mumol of NAS. Thus low doses of sphingolipids that were not
      effective in inhibiting ODC activity, reducing hyperplasia, or preventing
      epidermal papilloma development were, nonetheless, effective in inhibiting
      carcinoma development.

PMID- 9770724
TI  - Effects of diet and exercise on insulin, sex hormone-binding globulin, and
      prostate-specific antigen.
AB  - A diet high in fat has been linked to prostate cancer, possibly through an
      influence on hormones. Sex hormone-binding globulin (SHBG) binds androgens and is
      regulated in part by insulin. Diet and exercise can modify insulin levels,
      potentially affecting SHBG and the biologically available levels of androgens. To
      determine the effects of a low-fat (< 10% of calories), high-fiber diet plus
      daily exercise on insulin, SHBG, prostate-specific antigen (PSA), and serum
      lipids, we measured the levels of these factors in the serum of 27 obese men
      undergoing a three-week diet-and-exercise program. Insulin decreased from 222 +/-
      30 to 126 +/- 21 pmol/l (p < 0.01), and SHBG increased from 18 +/- 2 to 25 +/- 3
      nmol/l (p < 0.01). Body mass index decreased from 35 +/- 1.9 to 33.4 +/- 1.8
      kg/m2 (p < 0.01). PSA levels were normal and did not change significantly,
      although in a small subset of men (n = 3) with slightly elevated PSA levels (>
      2.5 ng/ml) all showed a decrease. The three-week diet-and-exercise intervention
      decreased insulin and lipid levels while increasing SHBG. The increase in SHBG
      would result in more testosterone being bound and, therefore, less of the
      androgen available to act on the prostate. The decrease in insulin might also
      decrease mitogenic activity in the prostate. The diet-and-exercise regimen did
      not have a significant impact on normal PSA levels. Although modest, these
      changes may be protective against the development of prostate cancer.

PMID- 9770725
TI  - Dietary sugar and lung cancer: a case-control study in Uruguay.
AB  - To examine whether dietary sugar modifies lung cancer risk, a case-control study
      involving 463 cases with lung cancer and 465 hospitalized controls was conducted
      in Uruguay in the period 1993-1996. Dietary patterns were assessed in detail
      using a 64-item food-frequency questionnaire, which allowed the calculation of
      total energy intake. After adjustment for potential confounders through a model
      that included tobacco smoking and total energy, total fat, vitamin C, and alpha
      carotene intakes, an increased risk for sugar-rich foods, total sucrose intake,
      sucrose to dietary fiber ratio, and glycemic index for lung cancer was observed
      (odds ratio for highest category of total sucrose intake = 1.55, 95% confidence
      interval = 0.99-2.44). When lung cancer was analyzed separately by cell type,
      odds ratios for small cell and large cell undifferentiated carcinoma were higher
      than those observed for squamous cell and adenocarcinoma of the lung. The joint
      effect of pack-years, total fat intake, and sucrose intake was associated with an
      increased risk of 28.3 (95% confidence interval = 13.4-59.7) for high values of
      the three variables. The study suggests that high sucrose intake could be an
      important risk factor in lung carcinogenesis. Further studies, both
      epidemiological and experimental, are needed to replicate the present findings
      and to clarify the mechanism(s) of sucrose intake in lung carcinogenesis.

PMID- 9770727
TI  - Effects of fatty acids on liver metastasis of ACL-15 rat colon cancer cells.
AB  - The effects of eicosapentaenoic acid [EPA; n-3 polyunsaturated fatty acid
      (PUFA)], linoleic acid (LA; n-6 PUFA), and palmitic acid (PA; saturated fatty
      acid) on 1,2-dimethylhydrazine-induced F344 rat colon carcinoma cells (ACL-15)
      were investigated in vivo and in vitro. The number and size of liver metastatic
      foci via a superior mesenteric vein injection of ACL-15 cells in F344 rats were
      significantly inhibited in the EPA-treated group compared with the LA-treated
      group (p < 0.01); the PA-treated animals and those fed commercial rodent chow
      (standard diet) demonstrated intermediate values. In a dot immunoblotting assay,
      vascular cell adhesion molecule 1 expression on ACL-15 cells was downregulated by
      EPA-ethyl ester treatment and upregulated by LA-ethyl ester treatment compared
      with the untreated control cells, whereas the expression of matrix
      metalloproteinase 1 and 2 was not influenced by the fatty acid ethyl esters. In a
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, EPA-ethyl
      ester suppressed ACL-15 cell growth in a schedule-dependent manner, and LA-ethyl
      ester showed schedule-dependent stimulation. In contrast, PA demonstrated no
      regulatory effect on cell growth at lower concentrations (< or = 5 mg/ml) but
      concentration-dependent inhibition at higher concentrations. According to our in
      vivo cell kinetic study, the difference in tumor growth at the metastatic site
      was due to different tumor cell proliferation rates; the cell loss rate was not
      altered. Therefore, the inhibitory effect of liver metastasis on ACL-15 cells by
      EPA can be explained by a decreased ability of tumor cell adhesion to the
      capillary bed (low expression of vascular cell adhesion molecule 1) and a lower
      potential of tumor cell proliferation (low mitotic rate) at the secondary site.

PMID- 9770728
TI  - 85th Annual meeting of the Swiss Society of Medical Radiology. Solothurn, 14-16
      May 1998. Abstracts.

PMID- 9770726
TI  - Estrogen profiles in postmenopausal African-American women in a wheat bran fiber
      intervention study.
AB  - High dietary fiber intake has been hypothesized to lower blood estrogen
      concentrations, an effect thought to be beneficial for decreasing breast cancer
      risk. This study investigated the association between dietary supplementation of
      wheat bran and circulating estrogen levels in postmenopausal African-American
      women participating in a community intervention trial. Seventeen postmenopausal
      women (aged 63 +/- 1.6 yr) participated in the study. Nutritional status was
      assessed and blood and 24-hour urine samples were collected before and after five
      to six weeks of daily supplementation of the diet with 35 g of wheat bran cereal
      (11.6 g insoluble dietary fiber) marked with 28 mg of riboflavin. Riboflavin
      confirmed that all postmenopausal participants adhered to the intervention
      protocol. Nine of the 17 postmenopausal women were taking some form of estrogen
      replacement therapy (PM-ERT). Baseline hormone levels in the PM-ERT group did not
      significantly change after the dietary intervention. Estradiol (96.8 +/- 20.3 vs.
      113.8 +/- 23.3 pg/ml), androstenedione (0.47 +/- 0.06 vs. 0.45 +/- 0.06 ng/ml),
      and sex hormone-binding globulin (SHBG, 107 +/- 13.5 vs. 106.6 +/- 13.3 nmol/l)
      levels remained constant. In the eight postmenopausal women who were not
      receiving exogenous hormones (PM), wheat bran consumption was not associated with
      predicted decreased levels of estradiol (25.7 +/- 2.7 vs. 31.0 +/- 1.9 pg/ml),
      estrone (38.3 +/- 10.1 vs. 39.3 +/- 10.6 pg/ml), and androstenedione (0.78 +/-
      0.08 vs. 0.68 +/- 0.11 ng/ml) or with increased concentrations of SHBG (35.2 +/-
      6.4 vs. 34.8 +/- 6.5 nmol/l). Participants receiving ERT had baseline and
      postintervention levels of estradiol and SHBG significantly higher and
      androstenedione significantly lower than those not receiving ERT. No association
      between wheat bran supplementation and hormone levels was found in PM or PM-ERT
      African-American participants. These results in postmenopausal women are in
      contrast to findings of earlier studies in premenopausal women indicating that
      wheat bran fiber decreases serum sex hormones. Estrogen levels in postmenopausal
      women are only 5-10% of those in premenopausal women; therefore, a high wheat
      bran fiber diet alone may not be sufficient to depress these low levels even
      further.

PMID- 9770729
TI  - [91st Annual meeting of the Swiss Society of Pediatrics. St. Gall, 11-13 June
      1998. Abstracts].

PMID- 9770730
TI  - Annual meeting of the Swiss Society of Infectology. Davos, 20-21 June 1998.
      Abstracts.

PMID- 9770731
TI  - Return of disabled-worker beneficiaries to the DI program: some insights from the
      new beneficiary followup.
AB  - Beneficiaries in the DI program may experience a recovery termination. What
      factors affect their reentitlement to DI benefits? Data from the New Beneficiary
      Followup was used to model return to the DI program. Those former beneficiaries
      who had vocational or job training and paid work after the recovery termination
      showed a lesser tendency to return to the DI program. Younger individuals and
      those in the highest primary insurance amount quartile also showed a lesser
      tendency to return.

PMID- 9770732
TI  - Recent changes in earnings distributions in the United States.
AB  - In this article, the author uses large, Social Security administrative data sets
      to examine changes in earnings distributions in the United States over the 1980s
      and early 1990s. Because the earnings information contained in these data sets
      comes directly from the W-2 forms filed by employers, self-reporting errors and
      top-coding problems, common in other data used for this type of analysis, are
      minimized. Previous research has documented an increase in overall earnings
      inequality during the 1970s and the 1980s. While the author also observes that
      overall earnings inequality generally increased during the early to mid-1980s,
      his analysis finds that this upward trend in earnings inequality might have
      slowed, or reversed, during the late 1980s and early 1990s. The data suggest that
      within-group inequality for various race and/or gender subgroups of the
      population generally increased over the period examined, confirming the results
      of others and extending those findings into the early 1990s. Finally, the author
      finds that female earnings increased relative to male earnings over the entire
      period, while the earnings of Black males declined relative to the earnings of
      the other groups examined.

PMID- 9770733
TI  - [Is it possible to use the term "functional heart diseases"?].

PMID- 9770734
TI  - [An epidemiological assessment of ischemic heart disease and mortality in men
      over 70 in the population of Saint Petersburg].
AB  - AIM: To analyze prevalence of ischemic heart disease (IHD), main IHD risk factors
      and mortality in the population of males aged 70-79 and over 80 years. MATERIALS
      AND METHODS: The study included 209 males aged 70-79 years and 96 males over 80.
      All the males were examined for IHD and 3 main risk factors: blood hypertension,
      hyperlipidemia and smoking. RESULTS: Incidence of IHD was about similar in both
      age groups. For 3.5 years of follow-up in the group of 80-year-olds mortality was
      2 times that of the group of 70-79-year-olds. The presence of IHD in the groups
      was directly related to the presence of 2 or 3 risk factors, especially in the
      group aged 70-79 years. In the group of 80-year-olds and older combination of IHD
      with affection of cerebral vessels was a poor prognosis sign. CONCLUSION: Factors
      deteriorating prognosis in males over 70 were: macrofocal myocardial infarction
      in anamnesis, atherosclerosis of the coronary and cerebral arteries.

PMID- 9770735
TI  - [The effect of the blood serum cholesterol level on the late prognosis of
      stenocardia in men 40-59 years old without arterial hypertension].
AB  - AIM: To investigate effects of total cholesterol levels in the serum (TC) on
      angina pectoris (AP) lethality in males. MATERIALS AND METHODS: The study of 112
      males aged 40-59 years with AP without myocardial infarction and blood
      hypertension lasted for 30-35 years. The examination included determination of
      lipid-protein blood spectrum, ECG at rest and exercise, other tests. By initial
      TC levels 98 patients were divided into 2 equal subgroups. Causes of death were
      ascertained at autopsy (72.0%) or records or regional death and birth
      registration offices were used. Reliable information was obtained for 98 of 112
      patients (87.5%). RESULTS: At the end of the study 8 of 98 patients were alive
      (8.2%). In the subgroup with low TC, 2 patients were alive, 47 decreased patients
      lived, on the average, 69.4 +/- 1.4 years. In the subgroup with high TC, 6
      patients were alive, 43 died at the age 71.2 +/- 1.4 years. CONCLUSION:
      Individual approach rather than populational is needed for correction of total
      cholesterol in middle-age and elderly patients with angina pectoris.

PMID- 9770736
TI  - [The reserve potentials of patients with ischemic heart disease who live under
      the conditions of an arid zone].
AB  - AIM: The study of physical performance of ischemic heart disease (IHD) patients
      in comfortable and uncomfortable (summer) weather conditions. MATERIALS AND
      METHODS: Systemic reserves were assessed by physical performance tests in
      comfortable weather (equivalent-effective temperature--EET 18-24 degrees C) and
      in heat discomfort (EET 25-30 degrees C), i.e. in summer when atmospheric oxygen
      is low (hyperthermic hypoxia). RESULTS: In uncomfortable weather, compared to
      comfortable one, general performance was significantly reduced evidencing
      uneffective function of the cardiovascular system. Comparison of the main
      ergometric parameters under the same load provides more accurate definition of
      the same trends in dynamics. CONCLUSION: General reserve in IHD patients is
      reduced under conditions of heart discomfort.

PMID- 9770737
TI  - [A comparison of the hypolipidemic action of probucol at doses of 500 and 1000
      mg/day in moderate hyperlipoproteinemia].
AB  - AIM: Evaluation of effectiveness of hypolipidemic action of probucol in doses 500
      and 1000 mg/day and comparison of probucol blood concentrations on the treatment
      month 3 and 6. MATERIALS AND METHODS: Probucol (Akrikhin, Russia) was given to 41
      patients with primary hypercholesterolemia in a dose 500 mg/day. 3 months later
      the patients were divided into two groups. Group 1 patients exhibited a > 10%
      decrease in cholesterol levels and continued to take probucol in the dose 500
      mg/day. Group 2 patients were crossed over to higher cholesterol dose--up to 1000
      mg/day. Lipids levels were measured by enzyme tests, apoproteins--by
      immunoturbidimetry and immunodiffusion, probucol concentrations--by high
      performance liquid chromatography. RESULTS: After 3 months of treatment,
      cholesterol lowered by 14.3 and 9.2% in groups 1 and 2, respectively. After 6
      months, by 19.7 and 12.9%, respectively. Probucol concentrations in blood were
      higher after 6 months of treatment than after 3 months in both groups. No
      significant differences existed between the groups by probucol concentrations in
      3 and 6 months. CONCLUSION: Hypolipidemic effect of probucol depended on the
      individual features of lipoproteins metabolic disorders rather than the drug
      blood concentration. Larger probucol doses fail to reduce cholesterol further.

PMID- 9770738
TI  - [The calcium antagonists diltiazem and nifedipine: a comparison of their efficacy
      in single and long-term use in patients with stable stenocardia of effort].
AB  - AIM: To compare efficacy of diltiazem and nifedipine in single dose and long-term
      treatment. MATERIALS AND METHODS: A randomised double-blind cross-over study
      enrolled 17 patients suffering from coronary heart disease (CHD) with stable
      angina of effort (SAE). For 1 month, each patient received diltiazem and
      nifedipine (60-90 mg 4 times a day and 20-30 mg 4 times a day, respectively). The
      effect was assessed by the pharmacodynamic test after the initial dose and in the
      end of each treatment course. RESULTS: In 14 eligible patients both drugs reduced
      the number of SAE attacks and nitroglycerin tablets, diltiazem efficiency being
      somewhat higher. Single doses of diltiazem and nifedipine produced the same
      action. In long-term treatment nifedipine effect became shorter, diltiazem effect
      did not change. Before the morning dose of nifedipine (11.5 hours after the
      previous dose) exercise tolerance of this drug worsened. This may be due to
      withdrawal syndrome. As to diltiazem, its exercise tolerance improved.
      CONCLUSION: In long-term treatment of CHD with SAE diltiasem is more effective
      and safe than nifedipine.

PMID- 9770739
TI  - [The differentiated therapy of paroxysms of atrial fibrillation and flutter in
      patients with ischemic heart disease in relation to the duration of the
      arrhythmia before the start of treatment].
AB  - AIM: To ascertain optimal antiarrhythmic therapy (AAT) in paroxysms of atrial
      fibrillation (AF) and atrial flutter (AFl) basing on their pretreatment duration.
      MATERIALS AND METHODS: A total of 2851 coronary heart disease (CHD) patients with
      AF and AFl paroxysms aged 40-75 years were treated from 1982 to 1996. The
      patients received sublingual or oral drugs (anaprilin, ethacizine, quinidine,
      etc.) or intravenous antiarrhythmic drugs (ritmilen, isoptin, novocainamide,
      etc). RESULTS: In pretreatment duration of AF and AFl up to 3 hours more
      pronounced effect was observed with sublingual and intravenous antiarrhythmic
      drugs. In the paroxysm duration up to 6 days, maximal antiarrhythmic
      effectiveness occurred in the use of intravenous antiarrhythmic drugs or
      quinidine, quinidine + verapamil. In the paroxysm duration from 7 days to several
      months, positive effect was achieved only in administration of quinidine or
      quinidine + verapamil. CONCLUSION: The principle of differentiated therapy of AF
      and AFl in CHD patients depending on the paroxysm duration before treatment
      allows choice of adequate therapy by enhancing its antiarrhythmic and weakening
      arrhythmogenic effects.

PMID- 9770740
TI  - [Gopten (trandolapril) in the treatment of chronic heart failure in patients with
      ischemic heart disease].
AB  - AIM: To investigate clinical efficacy of angiotensin-converting enzyme inhibitor
      trandolapril and its effects on myocardial function. MATERIALS AND METHOD: 20
      patients with ischemic heart disease (IHD) aged 33-74 years with chronic cardiac
      failure NYHA class II-IV. 4 of them survived myocardial infarction. In addition
      to the routine tests, the patients underwent echocardiography, radionuclide
      ventriculography. Trandolapril was given once a day for 28 days in a dose 2 mg,
      then a repeat examination was performed. RESULTS: Trandolapril produced a
      subjective effect in 80% of patients. There was also improvement of hemodynamic
      parameters, an increase in the ejection fraction, sensitivity to nitroglycerin,
      decline of asynchrony. The drug was well tolerated. CONCLUSION: Trandolapril
      (Gopten) is effective in IHD patients with chronic cardiac failure.

PMID- 9770742
TI  - [Central hemodynamics as dependent on the method of bicycle exercise in
      sanatorium patients who have had a myocardial infarct].
AB  - AIM: To study central hemodynamics response to bicycle exercise with optimal
      pedalling rate (OPR) and in free-choice regimen of pedalling as regards the
      initial pedalling rate in postmyocardial infarction (PMI) patients on sanatorium
      treatment. MATERIALS AND METHODS: Bicycle ergometry and tetrapolar rheography
      examinations were performed in 124 PMI male patients. Bicycle exercise was
      carried out in three regimens: a) optimal pedalling rate (1), b) muscular load
      chosen by the patient at the first training kept further for daily training (2),
      c) free-choice daily load (3). RESULTS: In OPR 30 and 45 rpm, patients on regimen
      3 improved their myocardial contractility both at rest and exercise. In OPR 60
      rpm, exercise in regimen 1 was more effective. Regimen 2 was not effective.
      CONCLUSION: Hemodynamic effects were most pronounced (improved myocardial
      contractility in more effective cardiac performance) in the regimen of OPR 60
      rpm.

PMID- 9770741
TI  - [HLA haplotypes in young myocardial infarct patients (a family study)].
AB  - AIM: Summarization of the results of family studies of inherited predisposition
      to myocardial infarction (MI) in young subjects from families with antigen Cw4 in
      phenotype. MATERIALS AND METHODS: Young probands (32, 37 and 46 years of age)
      with MI and the family members were examined. RESULTS: Antigen Cw4 predicts MI in
      young males living in the city of Kazan with MI hereditary load. CONCLUSION: The
      findings enable localization of at least one gene involved in development of
      hereditary predisposition to MI in the group of HLA link on the short arm of
      human chromosome 6.

PMID- 9770743
TI  - [Experience in using acupuncture reflexotherapy combined with weight-reducing
      diet therapy in hypertension].
AB  - AIM: To study the effectiveness of acupuncture in combination with unload diet
      against hypertension. MATERIALS AND METHODS: 137 patients with mild hypertension
      have undergone unload diet therapy or therapeutic fasting in combination with
      acupuncture. Acupuncture therapy was carried out according to the physiological
      model. The unload diet therapy was performed according to the method of Iu. S.
      Nikolaev and consisted of voluntary fasting. RESULTS: The treatment resulted in a
      decrease of cholesterol levels and blood pressure, positive trend in ECG. For 3
      years 20 patients with mild hypertension had normal blood pressure. They kept on
      diet, had short-term courses of fasting, exercised in free-choice regimen.
      CONCLUSION: Acupuncture in combination with diet therapy are recommended for
      treatment of blood hypertension. They can be used alone or in combination with
      drug therapy.

PMID- 9770744
TI  - [The use of aspirin in patients with primary pulmonary hypertension].
AB  - AIM: To investigate aspirin efficacy in patients with primary pulmonary
      hypertension (PPH) after a course of prostaglandin E-1 (PE) treatment. MATERIALS
      AND METHODS: 12 PPH patients (mean age 35.7 +/- 2.5 years) having the disease for
      6.7 +/- 1.1 years were assigned to a 6-month course of aspirin treatment in a
      dose 100 mg/day in combination with calcium antagonist isradipin. All the
      patients have previously undergone 21-day PE treatment (vasaprostan). Before and
      after the treatment, the patients were examined clinically and biochemically.
      RESULTS: As shown by ECG, chest x-ray, bicycle exercise, aspirin used in
      combination with isradipin led to stabilization of the disease. Platelet
      aggregation also remained stable, thromboxan B2 and endothelin-1 levels went
      down. Low doses of aspirin allowed to avoid side effects typical for this drug.
      CONCLUSION: Use of aspirin in a dose 100 mg/day in combination with calcium
      antagonists to treat primary pulmonary hypertension is justified.

PMID- 9770745
TI  - [The connection between late ventricular potentials and ventricular arrhythmias
      in hypertension patients with different forms of myocardial hypertrophy].
AB  - AIM: To estimate the incidence of late ventricular potentials (LVP) and their
      implication in cardiac arrhythmia. MATERIALS AND METHODS: 53 patients with blood
      hypertension stage II (mean age 50 +/- 1 years) having symmetric (n = 23) and
      asymmetric (n = 15) left ventricular hypertrophy as well as 15 patients free of
      hypertrophy underwent conventional 12-lead ECG, Holter monitoring,
      echocardiography and late potentials (LP) recording using signal-averaged high
      resolution ECG. RESULTS: LP occurred more often in asymmetric myocardial
      hypertrophy than in symmetric one. There was no strong correlation between LP and
      ventricular arrhythmias except patients with symmetric myocardial hypertrophy.
      CONCLUSION: In patients with hypertension stage II late potentials seem to arise
      due to increased hypertrophic myocardium depolarization time, myocardial fibrosis
      and local intramural blockades.

PMID- 9770746
TI  - [Difficulties in the diagnosis of recurrent rheumocarditis after a history of
      subacute infectious endocarditis].

PMID- 9770747
TI  - [The clinical significance of disorders in the hemostatic system in infectious
      endocarditis].
AB  - AIM: Study of blood clotting to evaluate hemostatic disorders in infectious
      endocarditis (IE). MATERIALS AND METHODS: The trial included 124 patients with IE
      (61 males and 63 females aged 15-70 years). Primary and secondary IE was in 38
      and 62% of patients, respectively. RESULTS: Clinically evident hemostatic
      disorders were observed in 93(74.2%) cases. They manifested as intravascular
      platelet activation with development of hypercoagulatory status and chronic DIC
      syndrome. CONCLUSION: A differentiated approach is advisable to correction of
      thrombotic disorders in IE basing on the severity of blood coagulation
      impairment.

PMID- 9770748
TI  - [Hospital infectious endocarditis and endocarditis in drug addicts].
AB  - AIM: To specify etiology and clinical course of nosocomial infectious
      endocarditis (IE) and IE of drug addicts (AIE). MATERIALS AND METHODS: 8 cases of
      AIE and 27 IE cases after various invasive interventions (nosocomial
      endocarditis). RESULTS: Among causing agents of IE and AIE were Staphylococcus
      aureus, Proteus, Escherichia coli, Pseudomonas aeruginosa, anaerobic microflora,
      pathogenic fungi. AIE is characterized by affection of the tricuspid valve,
      pulmonary artery thromboembolism. Among nosocomial endocarditides are frequent IE
      of the replaced valve, caused by infection of venous catheters, dental
      manipulations, chronic hemodialysis. IE and AIE are most frequently treated with
      the following antibiotics: ampicilin, gentamycin, augmentin, unasin,
      cephalosporins, rifadin, ciprofloxin, tienam. CONCLUSION: Nosocomial IE and AIE
      have drawn much attention in the last decade because of development of new
      complex invasive treatments and expansion of narcomania.

PMID- 9770749
TI  - [The surgical treatment of heart defects in active infectious endocarditis].
AB  - AIM: To elucidate significance of early diagnosis and results of surgical
      treatment of valvular defects in active infectious endocarditis (AIE). MATERIALS
      AND METHODS: Surgical outcomes were analyzed for 437 AIE patients with active
      AIE. The operation was made 10 months, on the average, after AIE onset. RESULTS:
      Total hospital lethality made up 11.2%. Total 5-year survival with account for
      hospital death was 77-80% in replacement of one valve and 61.6% in replacement of
      two valves (mitral and aortic). In natural course of the disease it was 16%.
      CONCLUSION: There was a direct relationship between hospital lethality and
      admission condition of the patients, advance of the inflammation. This urges
      early AIE detection and performance of operation before development of
      irreversible changes in the myocardium and other organs.

PMID- 9770750
TI  - [The medical rehabilitation of patients with an artificial pacemaker].
AB  - AIM: To study prognostic significance of individual rehabilitation of patients
      with pace-maker with account for leading cardiac syndromes. MATERIALS AND
      METHODS: 375 patients with artificial pace-maker were treated in a cardiological
      hospital for cardiac failure, blood hypertension, angina pectoris, cardiac
      arrhythmias. RESULTS: Congestive heart failure, blood hypertension, secondary
      cardiac arrhythmia, angina of effort were diagnosed in 57.4, 44.4, 33.0. 30.6% of
      the studied patients with artificial pace-maker. The patients died primarily of
      cardiac diseases, cancer and complications of cardiac pacing (71.3, 14.9 and 6.7%
      of cases, respectively). CONCLUSION: Aftercare of patients with pace-maker should
      be performed in groups of follow-up (5 groups) according to specially designed
      programs of diagnostic, therapeutic and prophylactic measures.

PMID- 9770751
TI  - [The late results of dispensary observation in systemic lupus erythematosus].
AB  - AIM: Analysis of a 12-year follow-up SLE patients. MATERIALS AND METHODS: In the
      course of a 12-year follow-up of 104 SLE patients the following tests were made:
      biochemical (acute-phase blood proteins), immunological (circulating immune
      complexes, IgA, IgM, IgG, complement system, rheumatoid factor), functional (ECG,
      echoCG) and others. The authors also made correction of the maintenance therapy,
      determined indications for pulse-therapy with glucocorticosteroids and
      cytostatics, extracorporeal and hospital regimens. RESULTS: 10-year survival
      reached 63.4%. 21.5% of patients died. Main causes of death were acute
      disturbance of cerebral circulation, chronic renal failure, sepsis, acute
      myocardial infarction, autoimmune hemolytic anemia. Age under 26 years, male sex,
      renal lesion with nephrotic syndrome, skin lesions combined with
      cerebrovasculitis, polyserositis, absence of chemotherapy with
      glucocorticosteroids in doses up to 15 mg/day, cytostatics, of plasmapheresis or
      pulse-therapy indicated poor prognosis. SLE ran favourably more frequently in
      females, at age over 37, duration of the disease at least 10 years,
      glucocorticosteroids intake in doses 20 mg/day and higher. CONCLUSION: Follow-up
      is an important element in the complex of rehabilitation measures in SLE
      patients.

PMID- 9770752
TI  - [The diagnosis and treatment of a secondary antiphospholipid syndrome in systemic
      lupus erythematosus].
AB  - AIM: The study of incidence of clinico-laboratory signs of antiphospholipid
      syndrome (APLS) and the results of its treatment in SLE. MATERIALS AND METHODS:
      Out of 120 patients with verified SLE, 13 (10.8%) had the signs of APLS. They
      underwent additional tests (platelet and lupus blood anticoagulant assays,
      assessment of immunity). RESULTS: APLS treatment consisted of suppression of
      antiphospholipid antibodies production by glucocorticosteroids and cytostatics,
      removal of antibodies by means of plasmapheresis, HBO therapy of thromboses and
      vascular defects. APLS in SLE frequently manifested with arterial thromboses,
      cerebrovasculitis, livedo, thrombocytopenia, lupus anticoagulant. CONCLUSION:
      Combined treatment of APLS in SLE improves the disease prognosis and prolongs
      life span.

PMID- 9770753
TI  - [Osteogenesis imperfecta in the rheumatologist's practice].

PMID- 9770754
TI  - [Clonorchiasis in the therapist's practice].

PMID- 9770755
TI  - [Hypertensive crises].

PMID- 9770756
TI  - [New prospects for the treatment of atherosclerosis: garlic preparations].

PMID- 9770757
TI  - [The complex quantitative assessment of right ventricular function: the
      potentials of echocardiography].

PMID- 9770758
TI  - [The therapeutic potentials of antileukotriene preparations in bronchial asthma
      patients].

PMID- 9770759
TI  - [Drug-induced stomach ulcers--the views of recent years].

PMID- 9770760
TI  - Government announces strategy for the control of TB in cattle.

PMID- 9770761
TI  - Welfare aspects of broiler breeder production.

PMID- 9770762
TI  - Newcastle disease outbreaks in domestic fowl and turkeys in Great Britain during
      1997.
AB  - Between January 6 and April 23, 1997, 11 outbreaks of Newcastle disease were
      confirmed in Great Britain, four in broiler chickens and seven in turkeys.
      Although the viruses isolated gave intracerebral pathogenicity indices in day-old
      chicks between 1.65 and 1.95, the clinical signs of disease in field infections
      were variable and not always associated with high mortality, especially in
      turkeys. Epidemiological investigations indicated that the majority of the
      outbreaks occurred as a result of secondary spread by human agency from two or
      more primary infected flocks. The presence of similar outbreaks in Scandinavian
      countries in 1996 and the unusual patterns of movement of migratory birds at the
      end of 1996 and beginning of 1997 suggest they may have been responsible for the
      primary introduction of the causative virus into Great Britain.

PMID- 9770763
TI  - A review of the road transport of slaughter sheep.
AB  - The transport of farm animals has been the subject of much research in recent
      years. This paper reviews the past and recent scientific literature pertinent to
      the road transport of slaughter sheep. The state of knowledge is summarised and
      recommendations for best practice based upon this are given. Areas which require
      further work are also identified.

PMID- 9770765
TI  - Cerebellar abiotrophy in a pedigree Charollais sheep flock.

PMID- 9770764
TI  - Matrix metalloproteinases 2 and 9 in canine rheumatoid arthritis.
AB  - Matrix metalloproteinases (MMPs) are considered important mediators of tissue
      damage in joint diseases. The levels of MMPs 2 and 9 were measured in samples of
      synovial fluid from 20 joints in seven dogs with rheumatoid arthritis by gelatin
      zymography. The results were compared with the actual gelatinolytic activity of
      the fluid measured in a gelatin-degradation ELISA. The gelatinolytic activity in
      synovial fluid from arthritic joints was markedly greater than that in fluid from
      disease-free joints. The zymographic activity attributable to MMP-9 (identified
      by Western blotting) was absent from synovial fluid from control joints but
      prominent in fluid from arthritic joints, and in these joints the presence of a
      75 kDa form of MMP-9 was correlated with the gelatinolytic activity of the fluid
      measured by the ELISA (r = 0.81, P < 0.05). Synovial fluid from one dog with
      rheumatoid arthritis was examined before and after treatment with
      corticosteroids. After treatment its zymographic pattern had returned to normal.

PMID- 9770766
TI  - Use of a PCR assay for Taylorella equigenitalis applied to samples from the
      United Kingdom.

PMID- 9770767
TI  - Reduced fertility after artificial insemination in a ram with a high incidence of
      knobbed acrosomes.

PMID- 9770768
TI  - Neospora caninum-associated abortion in a dairy herd in Argentina.

PMID- 9770769
TI  - Feeding wild birds.

PMID- 9770770
TI  - Calf processing aid scheme.

PMID- 9770771
TI  - Bluetongue research in China.

PMID- 9770772
TI  - Vets, stress and CPD.

PMID- 9770773
TI  - What is your diagnosis?

PMID- 9770774
TI  - Seasonal influences on the functional expression of the endogenous L-type Ca2+
      channels in Pleurodeles oocytes: role of cAMP?
AB  - We have investigated the seasonal regulation of the Ba current (IBa) through the
      L-type Ca2+ channels in Pleurodeles oocytes and its relation with the
      intracellular cAMP level. IBa-density remained relatively constant from January
      to February, increased from March to April (with a maximum increase in March) and
      decreased from May to July. While the permeable cAMP analogue 8Br-cAMP reduced
      IBa during the breeding season, it was without effect during the resting season.
      However, IBa recorded during the two seasons was increased by a dihydropyridine
      agonist Bay K 8644 and blocked by cadmium. The main conclusion is that the
      seasonal reduction in the L-type Ca2+ current amplitude may be correlated with a
      high intracellular cAMP level and may account for the inability of oocytes to
      mature during the resting season.

PMID- 9770775
TI  - Hyaluronic acid enhances induction of the acrosome reaction of human sperm
      through interaction with the PH-20 protein.
AB  - When capacitated human sperm were treated with hyaluronic acid (HA) for 30 min
      prior to the addition of progesterone or solubilised human zonae pellucidae,
      there was a significant increase in the percentage of acrosome reactions.
      Progesterone treatment alone increased acrosome reactions from 10.5% to 21.8% and
      pretreatment with 100 micrograms/ml HA resulted in 33.0% acrosome reactions. With
      zonae pellucidae treatment alone the increase was from 9.0% to 23.5% and with HA
      pretreatment it was 48.8%. HA treatment alone had no direct effect on acrosome
      reactions, and the enhancing effect of HA was not removed when sperm were washed
      prior to the addition of either acrosome reaction agonist. Experiments with sperm
      5 min after HA treatment demonstrated that enhancement of acrosome reactions was
      apparent as early as 1 min after addition of zonae and within 5 min after
      addition of progesterone. When sperm were pretreated with Fab fragments of anti
      PH-20 IgG, then with HA and then with progesterone or zonae pellucidae, there was
      no enhancement of the acrosome reaction. Fab treatment did not induce acrosome
      reactions and did not interfere with the action of either agonist in the absence
      of HA. Sperm that were treated with HA had significantly higher intracellular
      calcium levels, and pretreatment with Fab reduced this increase to 42.7%.
      Addition of progesterone to HA-treated sperm was followed by another large
      increase in intracellular calcium, which was lower when sperm were pretreated
      with Fab. These results suggest that HA interacts with the PH-20 protein to
      increase basal levels of intracellular calcium and thereby potentiates the
      acrosome reaction. The data support the hypothesis that HA in the cumulus matrix
      may act to prime the fertilising sperm for induction of the acrosome reaction by
      constituents of the cumulus and/or zona pellucida.

PMID- 9770776
TI  - Fluorophore toxicity in mouse eggs and zygotes.
AB  - Ion-sensitive fluorophores are commonly used for quantitative measurements of
      intracellular ion concentrations. However, both the method of intracellular
      loading--which for many fluorophores involves endogenous esterase-mediated
      removal of hydrophobic groups such as acetoxymethyl esters (AM)--and fluorescence
      excitation of fluorophores in the cell, can produce toxic metabolites and
      reactive species. Techniques used to measure intracellular ion concentrations in
      mammalian eggs and embryos are being increasingly employed, yet little
      information is available about any detrimental effects of the use of
      fluorophores. We have therefore used in vitro fertilisation (IVF) to assess
      potential fluorophore toxicity in mouse eggs, and whole cell patch-clamp
      recordings to detect fluorophore-associated membrane damage in zygotes. Four
      fluorophores were examined: SNARF-1 and BCECF (pH indicators), Fura-2 (Ca2+) and
      MQAE (Cl-). Cleavage of AM groups alone had no effect either on the success of
      IVF or on membrane electrical properties of mouse zygotes. Intracellularly loaded
      BCECF, SNARF-1 and Fura-2 followed by fluorescence excitation were not cell-toxic
      under the conditions examined. In contrast, MQAE demonstrated significant
      toxicity both alone and in combination with fluorescence excitation.

PMID- 9770777
TI  - The site of fertilisation determines dorsoventral polarity but not chirality in
      the zebra mussel embryo.
AB  - The dorsoventral polarity of unequally cleaving spiralian embryos becomes
      established at an early stage. The factors determining the position of the
      dorsoventral axis are still unknown. We present data showing that the sperm entry
      point (SEP) in both normal development and under experimental conditions
      determines the position of the first cleavage furrow in Dreissena embryos. The
      position of the spindles at second cleavage is directed by the site of
      fertilisation also, and the large, dorsal D quadrant of the 4-cell stage always
      forms opposite the SEP. The spiral chirality at third cleavage seems to be
      independent of both the fertilisation point and the arrangement of the quadrants.
      Dextral and sinistral third cleavages are found in a single egg batch, but
      sinistral cleavages prevail. We postulate that two factors coordinate the proper
      positioning of the dorsoventral axis. The sperm entry point as an epigenetic
      factor determines the dorsal side of the embryo. But since the dorsoventral axis
      forms oblique to the first cleavage furrow, this first decision is still
      ambiguous, and a second decision is required that, due to the alternative
      chirality of spiral cleavage, finally sets up the dorsoventral axis.

PMID- 9770778
TI  - Impaired development of zygotes with uneven pronuclear size.
AB  - The correlation between human zygote morphology and chromosomal anomalies after
      cleavage has not been well characterised. Commonly observed morphological
      qualities at the zygote stage have provided little insight into further
      development, and therefore selection for cryopreservation or transfer appears to
      be less specific than that at later stages of preimplantation development. The
      purpose of this work was to evaluate the relationship between aberrant pronuclear
      morphology and chromosomal anomalies after cleavage. Monospermic zygotes
      exhibiting two pronuclei where diameters differed by at least 4 microns were
      found to arrest at a significantly higher rate than zygotes with pronuclear
      diameters differing by less than 4 microns. In addition, a higher incidence of
      day 2 multinucleation was observed. Embryos deriving from zygotes with dysmorphic
      pronuclei that were not replaced or cryopreserved by day 3 of development were
      separated and fixed for fluorescence in situ hybridisation analysis of
      chromosomes X, Y, 13, 18 and 21. A significantly higher incidence of mosaicism
      was found in this group compared with others that had developed from zygotes with
      normal pronuclear morphology. Although the mechanism leading to this form of
      divergent pronuclear morphology is unclear, results suggest a correlation with
      oocyte cytoplasmic immaturity.

PMID- 9770779
TI  - Intracytoplasmic sperm injection in the rat.
AB  - We applied intracytoplasmic sperm injection (ICSI) to the rat comparing three
      different sperm injection techniques: conventional setup with a sharp needle
      bearing a spike (method 1), combination of partial zona dissection (PZD) needle
      and blunt pipette (method 2) and piezo-injection using a blunt pipette (method
      3). We also investigated the timing of sperm pronuclear formation after
      injection. Survival rates after injection were 8%, 24% and 71% for the methods 1,
      2 and 3, respectively. All surviving oocytes formed pronuclei by about 6 h after
      injection. Although the survival and activation rates following sperm injection
      using piezo-injection were high, the incidence of normal fertilisation, as
      evidenced by second polar body extrusion and formation of two pronuclei, was only
      10%. The vast majority of the zygotes were multinucleated, although most of them
      subsequently underwent cleavage. Fixation and staining of injected oocytes at
      different times after injection revealed that replacement of sperm nuclear
      protamines by histones takes place by 15 min after injection, sperm head swelling
      occurs within 0.5-1 h after injection and pronuclei become fully developed by 7 h
      after injection. Although the rate of normal fertilisation in the rat following
      ICSI was low under the present experimental conditions, the results indicated
      that direct ICSI using a piezo-driven pipette would be a potentially valuable
      method of producing rat offspring.

PMID- 9770780
TI  - Soluble extracts from ascidian spermatozoa trigger intracellular calcium release
      independently of the activation of the ADP ribose channel.
AB  - We have injected soluble extracts of sperm from the ascidian Ciona intestinalis
      into oocytes of the same species to test whether these extracts can mimic the
      events of fertilisation. Injection of ascidian sperm extracts leads, after a
      delay of approximately 60 s, to a large calcium transient and repetitive pattern
      of calcium oscillations, mimicking the normal fertilisation response. The
      response was concentration-independent, suggesting a stimulatory mechanism in
      triggering the fertilisation response. We tested the pathway of calcium release
      in ascidian oocytes after injection of sperm extracts by preinjection of calcium
      release inhibitors. The data demonstrate that dual pathways to calcium release
      act at fertilisation in ascidians, as in other species. C. intestinalis oocytes
      are characterised by a ion channel in the plasma membrane that is gated uniquely
      by ADP ribose. We show that this channel is not gated by the injection of
      ascidian sperm extracts. Our data suggest that one metabolic pathway triggered by
      sperm, the release of nitric oxide, is not stimulated by sperm extracts and that
      several metabolic pathways are stimulated at fertilisation by more than one
      factor within sperm.

PMID- 9770781
TI  - Sperm plasma membrane receptors for the porcine oocyte plasma membrane.
AB  - In vitro fertilisation (IVF) was used to assess the ability of solubilised sperm
      plasma membrane (PM) proteins to inhibit the interaction of intact gametes. This
      is a first step before evaluating the ability of individual isolated proteins to
      competitively inhibit sperm-oocyte interaction as part of the process of studying
      the molecular events of fertilisation. Porcine oocytes were aspirated from
      ovaries, matured for 48 h in Medium 199, and the zona pellucida (ZP) was removed
      by exposure to acid Tyrode's solution. ZP-free matured oocytes were exposed to
      200-800 micrograms/ml sperm PM protein for 1 h prior to insemination and during
      gamete co-incubation. Twenty-four hours after insemination with 5 x 10(5)
      capacitated sperm/ml, the oocytes were fixed, stained and examined. Sperm PM
      protein clearly inhibited IVF in a concentration-dependent manner (r = -0.87).
      The inhibition index (I50%), representing the sperm PM protein concentration
      necessary to inhibit IVF to 50% of the control value, was 310 micrograms/ml.
      These results demonstrate that solubilised sperm PM protein inhibits the
      interaction of intact gametes as one might expect for receptor-ligand
      interactions. Furthermore, the complement of sperm PM proteins appeared maximally
      effective at a calculated concentration of 690 microns/ml, providing a foundation
      for further studies with individual proteins.

PMID- 9770782
TI  - Localisation of inositol trisphosphate and ryanodine receptors during mouse
      spermatogenesis: possible functional implications.
AB  - During spermatogenesis the activity of intracellular Ca(2+)-release channels is
      likely to play an important role in different specific cellular functions.
      Accordingly, messenger RNAs for the three inositol 1,4,5-trisphosphate receptor
      (IP3R) subtypes were found to be present throughout spermatogenesis.
      Immunocytochemical analysis revealed distinct distribution patterns of the mature
      IP3Rs during sperm differentiation. At early stages, IP3Rs are distributed
      throughout the cytoplasm, and as differentiation proceeds they become selectively
      localised to the Golgi complex. Consistently, spermatogonia underwent large
      intracellular Ca2+ release in response to thapsigargin (TG), while smaller
      responses were detected in late spermatocytes and spermatids. The distribution of
      IP3Rs and the larger Ca(2+)-release responses found in spermatogonia, suggest
      that IP3Rs may be involved in cell proliferation at this stage. This notion is
      supported by our observations in a spermatogenic cell line that depletion of
      intracellular Ca2+ pools using TG inhibits cell division, and that incubation
      with an IP3R-I antisense oligonucleotide completely inhibited proliferation.
      Furthermore, the three genes encoding ryanodine receptor proteins (RyRs) are
      expressed at all stages of spermatogenesis. However, immunocytochemical studies
      with specific antibodies against each of the RyR subtypes detected types 1 and 3
      in spermatogenic cells and only type 3 in mature sperm. In contrast to IP3Rs,
      RyRs remain scattered in the cytoplasm throughout differentiation. Functional
      responses to caffeine and ryanodine were absent in spermatogenic cells and in
      mature sperm. These findings suggest that IP3Rs have significantly more important
      roles in spermatogenesis than RyRs, and that one of these roles is crucial for
      cell proliferation.

PMID- 9770783
TI  - Xenopus laevis fertilisation: analysis of sperm motility in egg jelly using video
      light microscopy.
AB  - Xenopus laevis eggs are surrounded by an extracellular matrix consisting of a
      vitelline envelope, and three jelly layers, J1, J2, and J3 (from egg surface
      outward). The jelly layers vary in thickness (about 150, 15 and 200 microns for
      J1, J2 and J3 respectively) but all are translucent allowing observation of sperm
      penetration. Video microscopy demonstrated that sperm are able to penetrate and
      traverse J3 at velocities approaching 30 microns/s. Sperm swim through jelly in a
      corkscrew-like manner with their rotational and forward velocities being tightly
      coupled at about 30 degrees/micron forward travel. They are propelled by whip
      like power strokes involving hairpin bends in the flagellum that are generated
      every 180 degrees of rotation and which are propagated from base to tip. The
      overall trajectories of individual sperm are quite variable. Many sperm head
      directly for J2 but some do not, these swimming circumferentially, or even away
      from the egg surface. Most sperm (over 97%) that enter the jelly do not get to
      the egg surface but are stopped at a variety of positions within J3 or at the
      outer surface of J2. Efficient sperm penetration and passage through the jelly
      layers requires a low electrolyte concentration in the surrounding medium, and is
      inhibited by the lectin wheat germ agglutin (WGA) in a dose-dependent manner. WGA
      does not block sperm penetration of J3 but does block further progression towards
      the egg surface. This observation suggests that sperm motility within the jelly
      is dependent on the carbohydrate moieties of the large glycoconjugates present,
      and that their alteration by WGA binding accounts for the inability of sperm to
      reach the egg surface and fertilise the egg.

PMID- 9770784
TI  - The nature of the 'nucleolus precursor body' in early preimplantation embryos: a
      review of fine-structure cytochemical, immunocytochemical and autoradiographic
      data related to nucleolar function.
AB  - In mammals, the restoration of rRNA transcription after fertilisation is
      accompanied by a gradual differentiation of the nucleolar structure by a process
      called embryonic nucleogenesis. During cleavage, the nucleolar components appear
      sterically related to a class of nuclear bodies already detectable in pronuclei.
      These structures, due to their apparent function as centres of nucleolus
      formation, have been designated nucleolus precursor bodies (NPBs). It was found
      recently not only that the size and morphology of the NPBs differ among mammalian
      species, but that the pattern of embryonic nucleologenesis and even the molecular
      composition of different NPB compartments vary from one species to another.
      Accordingly we assumed that at least two definitely different types of NPBs
      exist, namely the mouse-type NPB and cow-type NPB. In the mouse-type NPB, the
      original compact material of the NPB remains detectable in the early functional
      nucleolus. This NPB core does not contain DNA or typical Ag-NOR nucleolar
      proteins. At the onset of rRNA transcription, the nucleolonema is formed at the
      periphery of the NPB. The cow-type NPB shows a homogeneous distribution of
      typical nucleolar proteins throughout its body from the pronucleolar to the early
      8-cell stage. At the beginning of rRNA transcription, the cow-type NPB is
      penetrated by perinucleolar DNA and rRNA synthesis is detectable deep inside the
      nucleolus. In this case, the entire NPB is readily transformed into a typical
      nucleolus. These processes are recognisable using fine-structure analysis of
      preimplantation mammalian embryos. For this reason this approach is often used as
      a method of evaluating the state of experimental embryos; in such studies, the
      species differences must be taken into account.

PMID- 9770785
TI  - [The welcoming address on the occasion of the 50th anniversary of the Scientific
      Society of Obstetrics and Gynecology].

PMID- 9770786
TI  - [The effect of surfactant therapy on the oxygen treatment of premature infants
      with HMD].
AB  - A retrospective study is carried out, including 61 premature newborns, admitted
      to the Intensive Care Unit of State Maternity Hospital from 1994 to 1996. The aim
      of the study is to establish the influence of surfactant therapy on the duration
      of oxygen therapy and on the incidence of BPD. Criteria for entry: birth weight
      below 1500 grams, gestational age up o 32 weeks, clinical signs and x-ray proof
      of RDS. EXCLUSION CRITERIA: major inborn malformations and IVH--grams i.v..
      Newborns are divided in 3 groups: 27 babies treated with Curosurf, 10 babies
      treated with Exosurf and 24 babies who received no surfactant. Results show that
      surfactant treated babies spent shorter time on ventilator support and oxygen
      therapy as a whole, the difference having high statistic level of significance in
      the Curosurf group. Surfactant therapy leads to lowering the incidence of oxygen
      dependency at 36 weeks post conception, especially in Curosurf treated babies.

PMID- 9770787
TI  - [Ultrasonic methods for determining the volume of amniotic fluid in a complicated
      pregnancy: improved methods for the prognosis of the perinatal outcome].
AB  - Semiquantitative measurement of amniotic fluid volume (AFV) was used to predict
      the pregnancy outcome. In 229 high risk pregnancies, the AFV was assessed by 4
      ultrasonographic methods, including our suggested one--the modified amniotic
      fluid index (MAFI). Abnormal perinatal outcome was defined as operative delivery
      sue to fetal distress (OD/FD), meconium passage, low 5 min. Apgar score,
      umbilical artery pH (< 7.2) and intrauterine growth retardation (IUGR). About
      26.2%, 32.8%, 37.6%, 30.6% and 16.6% cases of OD/FD, meconium stained fluid, low
      5 min. Apgar score, low pH and IUGR were identified with oligohydramnios compared
      with the normal fluid group, using MAFI (p < 0.000001). The MAFI showed higher
      significance than the other ultrasonographic (US) methods. With the relative
      screening performance the sensitivity of MAFI, amniotic fluid index (AFI),
      maximum vertical pocket (MVP) and tho-diameter pocket (TDP) depths were 91.9%,
      70.2%, 58.9% and 32.8% respectively with OD/FD. Our results suggest that the AFV
      assessment by MAFI may be superior to the other US techniques and it may used in
      the testing protocols of antepartum fetal surveillance.

PMID- 9770788
TI  - [The significance of the problem of umbilical cord prolapse during delivery].
AB  - The authors aimed at studying the significance of cord prolapse in modern
      obstetrics. 18836 deliveries were studied. These deliveries occurred during a 7
      year period (1990-1996) and a rate of cord prolapse of 0.106% was found (1 case
      in 941.8 deliveries). Cord prolapse was found in 20 deliveries of which 16 were
      singleton pregnancies and 4 multiple. 7 of the women were nulliparous and 13
      multiparous. The majority of patients were of gestational age 38-41 weeks--13
      (65.0%) 4 (20.0%) were between 30-37 gestational weeks and 3 (15.0%) were 42
      gestational weeks. Of the singleton pregnancies only one fetus was in a
      transverse lie, 8 were breech presentations and 7 vertex presentations. Delivery
      was accomplished by cesarean section in 2 (45.0%) cases. Of the 8 breeches 3 were
      delivered by CS, 4 vaginal manual delivery and one (1) by manual extraction. All
      multiple pregnancies were delivered vaginally normally. Of the singleton
      pregnancies only 2 were under 2000 g weight, Perinatal infant mortality rate in
      this group was 291.67% (7 of 24). Still births were 2 and they occurred
      intrapartially: one was a vertex presentation after refusal of CS, and the second
      -after breech extraction (1500 g birth weight). The authors conclude that in
      order to reduce the rate of cord prolapse indications for CS should be precisely
      revised for multiple pregnancies breech presentation.

PMID- 9770789
TI  - [The incidence and structure of perinatal mortality in Bulgaria].
AB  - An analysis of the rate, structure and the principle causes of the perinatal
      infant mortality during the last 7 years in Bulgaria is presented. The values of
      the analysed indices are compared with those of the period 1985-1990 year. The
      main causes in the structure of the perinatal infant mortality during the
      transitional period in Bulgaria are discussed.

PMID- 9770790
TI  - [The concentration of selenium in the maternal serum in cases of missed
      abortion].
AB  - The changes in the serum level of selenium in cases with pathologic pregnancies
      are still not clear. The aim of the present study was to determine whether serum
      selenium in cases with missed abortion differed from selenium concentration in
      serum during first trimester of normal pregnancy. Twenty-three women with missed
      abortion and 61 with normal pregnancy were included in the study. We found a
      statistically significant (p < 0.001) elevation of serum selenium level in cases
      with missed abortion (928 +/- 335 nmol/l) comparing with those with normal
      pregnancy (568 +/- 77 nmol/l). We discuss the possible mechanisms of the observed
      changes.

PMID- 9770792
TI  - [The Multiload--a modern intrauterine device].
AB  - In the first part of publication the authors make a profound review of history of
      development and qualities of Intra Uterine Devices/IUD's/. There are reflected
      the first steps dated from the ancient times to come to modern IUD's (Multiload,
      Copper T. Slimline). In Table 1 and 2 (on W.A.A. van Os) are represented single
      cases (pregnancy, expulsion and extracted IUD's) related to the modern
      intrauterine devices: MLCu 250 and MLCu 375 for the periods of 1, 3 and 5 years.
      In the second part the authors represent their scientific and practical results
      which has been obtained at the Bulgarian Family Planning and Sexual Health
      Association and the Ob./Gyn. Department of Medical University-Sofia. A
      retrospective research has been conducted on 406 women who delivered between 18
      and 42 years of age and to which MLCu 375 have been inserted. The so analyzed and
      presented results show very good qualities of MLCu 375 IUD. The cases' frequency
      corresponds to the one announced by the world leading practice of contraception.

PMID- 9770791
TI  - [Pregnancy outcome (perinatal mortality and morbidity) in women with diabetes].
AB  - In our study we have 313 cases--100 cases as a control group and 213 cases as a
      diabetic group. Different types of pregnancy outcome have been studied in these
      cases (perinatal mortality rate and perinatal morbidity). The most frequent
      morbidity is from: fetopathy diabetic, congenital malformation, respiratory
      distress syndrome, preterm delivery, intrapartum traumatic complications
      (shoulder dystocia, brachial plexus injury, intracranial bleeding, fracture of
      clavicle), hypoglycemia, hypocalcemia, hyperbilirubinemia.

PMID- 9770793
TI  - [Strategies in antibiotic prophylaxis in abdominal hysterectomy].
AB  - The following study presents the high effectiveness of the short-term antibiotic
      prophylaxis versus long-term in elective abdominal hysterectomy. The authors
      compare two groups of 68 patients each for a period of 10 months. In the first
      group 67 patients have received one antibiotic and one--a combination of two
      antibiotic per 24 hours. In the second group 66 patients have received one
      antibiotic and two patients--a combination of two antibiotics for a period of 3
      days. The two groups were compared using two clinical characteristics--axillary
      temperature and pulse, and also postoperative complications--vulnerary infections
      (parametrial, subfascial, and subcutaneous) The results demonstrate that in these
      cases the short-term antibiotic prophylaxis has higher effectiveness than the
      long-term one in the prevention of febrile complications and postoperative
      infections.

PMID- 9770794
TI  - [Cervical screening in Bulgaria. An analysis of the basic indices over the period
      1970-1994].
AB  - The aim of the present study was to analyze the results from the cervical
      screening in Bulgaria for the period 1970-1994, by studying the following
      indicators: incidence, mortality, frequency of carcinoma in situ and stage
      distribution of the cases with invasive cervical cancer. The relatively constant
      incidence and mortality until 1987 were evident, after that they shoved
      increasing and for 1994 they are 19.7% and 7.6% respectively. The similar is the
      data for the correlation carcinoma in situ/invasive cancer and for the stage
      distribution of the cervical cancer patients. The obtained results showed, that
      cervical cancer remain medico-social problem for our country, because the
      introduced in 1970 cervical cytological screening at the moment is not effective
      enough.

PMID- 9770795
TI  - [Ultrasonic follow-up of the endometrium in women with sterility after Serpafar
      treatment].
AB  - We investigated 25 women with anovulation or defects in the follicular growth
      after treatment with Serpafar for period of 6 months. During the first cycle
      investigation is without treatment and the patients were analysed for BBT
      follicular maturation endometrial thickness, cervical mucus, FSH, LH. For next 5
      month the patients are treated with Serpafar. We established that endometrial
      thickness is dynamic changes in every cycle. The comparison was done when the
      leading follicular diameter was 18-24 mm. CONCLUSION: There was not difference in
      endometrial thickness in treatment cycles nor a trend for thickness to increase
      or decrease. Probably the mechanism of ovulation and pregnancy rates after
      Serpafar is not connected with thickness of the endometrium.

PMID- 9770796
TI  - [Dilatation and curettage in women with abnormal uterine bleeding--an analysis of
      the histopathological findings].
AB  - The aim of this study is to analyse the histopathologic findings from the uterine
      cavity and the cervical canal among women who attended the gynecologic clinic of
      HMI Pleven for abnormal uterine bleeding. The study is retrospective and for a
      ten month period--from 01.03, 1996 to 31.12, 1996. After dilation and curettage
      under general anaesthesia histologic examination of the material was done in 161
      women aged 19 to 73 years. The patients were divided according to the
      pathomorphologic findings from the uterine cavity into 9 groups and into 5-
      according to the findings from the cervical canal. The analysis of the data shows
      that the peak of abnormal uterine bleeding is 48 years, and that of endometrial
      carcinoma--51 years. The relative ratio of pathologic findings from the uterine
      cavity, including endometrial polyps, simple, adenomatous and atypical
      hyperplasia and carcinoma of the endometrium is 47.2%.

PMID- 9770798
TI  - [Mistakes and errors in the diagnosis and initial treatment of extrauterine
      pregnancy].

PMID- 9770797
TI  - [The basement membrane proteins collagen type IV and laminin and the preinvasive
      reorganization of the stroma in carcinoma in situ of the cervix uteri].
AB  - The migration of tumor cells through the basal membrane (BM) is a key event in
      the cascade of tumor infiltration and metastasizing. The aim of the present study
      is to investigate BM proteins larniriin and collagen IV in cervical carcinoma in
      situ and the preinvasive reorganization of the underlying stroriia. 15 worileri
      with biopsy diagnosis of cancer in situ are studied. The immunohistochemical PAP
      reaction on fresh and parafiri sections is used. Light microscopically there are
      features of characteristic reorganization of the stroma lying under the
      neoplasia: neocapillarization next to BM and lack of vascular proliferation far
      away front it; localized swelling and expressed iriflariiriiatory irifiltrate in
      these regions. The immunolocalization of laminin and collagen type IV is
      important for the assessment of BM under the intraepithelial cancer.

PMID- 9770800
TI  - [The sudden and unexpected death syndrome in nursing infants].

PMID- 9770799
TI  - [Paget's disease of breast--a clinicomorphological analysis].
AB  - The aim of this study is to examine the differences between clinical and
      morphological diagnosis concerning morbus Paget of the breast. For period of 5
      years, 15 cases were clinically diagnosed as morbus Paget. Only 7 of them were
      pathologically confirmed. Clinical data and histological sections prepared from
      these patient's surgical materials were investigated. In 8 cases clinical
      diagnosis was different from pathological and in 3 cases only there have been
      clinical reasons for that. A condition is drawn, that Paget's disease of the
      breast is a rare illness, taking oneself with typical clinical manifestations,
      that sometimes are occurred and with other mammary neoplasms. This fact can lead
      to hyperdiagnosis.

PMID- 9770801
TI  - [HPV infection and its significance in cervical oncogenesis].

PMID- 9770802
TI  - [Sexual violence and the abuse of children and adolescents].

PMID- 9770803
TI  - [The polycystic ovary syndrome--its diagnosis and the therapeutic approach].

PMID- 9770805
TI  - [Myomectomy performed after Zoladex preparation with subsequent repair of the
      uterine wall via a balloon catheter in the uterine cavity].

PMID- 9770804
TI  - [Epilepsy and pregnancy].
AB  - Presented is a case of a 22-year-old pregnant woman in the ninth lunar month of
      pregnancy and with epilepsy from 10 years of age. The patient had been on therapy
      with barbiturates and carbamazepines for over ten years. She was hospitalized in
      the neurology department after having 5 grand mals in one day. After
      hospitalization she was observed to have Jackson-type feats of the left limbs
      that later on became generalized. In-between the feats she had left-sided
      reflector hemiparesis, and EEG data of an epileptic focus in the sensomotor
      region of the right hemisphere. The CT with contrast medium showed no pathologic
      changes. Sonography and cardiotocographic studies revealed no gross anomalies of
      the fetus, and adequate biometric data. Therapy was instituted with carbamazepin
      0.200 t.i.d. valproate 0.200 t.i.d. and mannitol i.v. l/kg body weight. On the
      seventh day of therapy emergency c.s. was performed and a viable fetus weighing
      2020 grams and in length 43 cm. was extracted. For three days after the operation
      the patient was on artificial ventilation. She was discharged on the twentieth
      day in a relatively good state and on maintenance therapy. The authors believe
      that the effect of pregnancy on epilepsy cannot always be foreseen. A precise
      titration of anticonvulsants to necessary for optimal control of epileptic feats
      during pregnancy.

PMID- 9770806
TI  - [The differential diagnostic criteria in metastatic ovarian tumors].
AB  - Ovaries often are a target organ for metastases from another primary locus,
      especially in young women in reproductive age. This review focuses on the
      diagnostic difficulties in distinguishing between primary and metastatic ovarian
      tumors.

PMID- 9770807
TI  - [The possibility for treating certain forms of endometrial and ovarian carcinomas
      with GnRH agonists].

PMID- 9770809
TI  - [The mechanical properties of the lungs in patients with congenital heart defects
      in the immediate postoperative period].
AB  - Static compliance and inspiratory resistance were assessed in 218 patients aged
      over 3 years after open-heart surgery for correction of congenital heart disease
      during the immediate postoperative period without complications. Cst in the
      immediate postoperative period in patients with Fallot's tetralogy,
      intraventricular septum defect, intraatrial septum defect, and incomplete form of
      atrioventricular communication was higher than in patients operated on for
      Fallot's tetralogy with a previous systemic-pulmonary anastomosis and pulmonary
      artery atresia, whereas Rinsp was virtually the same in all groups. Age-specific
      differences were noted. The data are recommended for use as reference values in
      stress.

PMID- 9770808
TI  - [The determination of cardiac output by the dilution of ultrasonic blood
      density].
AB  - The authors propose assessing cardiac output (CO) by diluting the blood
      ultrasonic properties. For measuring CO, the peripheral artery and vein were
      connected with a catheter, and ultrasonic flowmetric pickup was attached to the
      shunt. Indicator (0.9% sodium chloride) was injected into the central vein.
      Changes in the blood ultrasonic characteristics during the indicator flow were
      recorded by ultrasonic flowmeter. Dilution curves were computer processed. The
      method was tried in 7 experimental dogs and clinically in 11 patients and
      compared with the thermodilution method. The coefficient of correlation was 0.98
      in experiment and 0.97 in clinical trials. Dilution of ultrasonic density of the
      blood helps accurately assess the CO and is highly informative, which is
      confirmed by a strong correlation with the results of thermodilution. The method
      is simple, little invasive, realized using available equipment, the indicators
      are cheap and available, and repeated studies can be performed within short
      periods of time.

PMID- 9770810
TI  - [The assessment of microcirculation based on mathematical models of the
      hydrodynamics and oxygen transport in the microvessels (II)].
AB  - Our previous communication No. 1 presents a mathematical definition of dynamic
      hematocrit and rate of erythrocyte movement, based on microvessel hemodynamics
      model. Now we offer a mathematical model of convective diffusion oxygen transfer
      in the erythrocytic cylinder-plasma system. Another definition of erythrocyte
      movement rate is offered and a solution of two equations which permitted its
      definition by measured parameters. A series of practical formulae for estimating
      microhemodynamics is derived, which can be used in clinical practice. The
      proposed model has been used in cardiosurgery department of Research Center of
      Surgery.

PMID- 9770811
TI  - [A strategy and procedure for the antibacterial therapy of abdominal sepsis].
AB  - Offers a protocol of antibacterial therapy of abdominal sepsis in surgical
      patients. Analyzes the principal etiological agents of abdominal septic
      complications. Presents optimal schemes of antibacterial therapy of abdominal
      sepsis. Pays special attention to choice of antibiotics in different clinical
      situations.

PMID- 9770812
TI  - [Carbapenems (thienam and Meronem). Their clinical and economic efficacy].
AB  - The authors describe 229 cases of carbapenem use in intensive care wards. Tienam
      was used in 205 cases since 1993, meronem in 24 cases since 1996. There were 149
      men and 80 women aged 15-76 years (mean age 46.4 +/- 0.7 years). Carbapenemes
      were administered by 5-7-day courses in a daily dose of 2-6 g (2-4 g for tienam
      and 2-6 g for meronem). Carbapenemes were administered as monotherapy; in 196
      cases nisoral was added to antibiotic therapy starting from day 3 as an
      antimycotic agent. Bacteriological studies were carried out in 367 patients (413
      inoculations). Sensitivity of cultured microflora to disks with tienam (329
      tests) and meronem (97 tests) showed their high activity towards gram-positive
      and gram-negative flora. The results were less demonstrative in cerebral
      abscesses, which is explained by specific pharmacokinetics of tienam. Analysis of
      the cost/efficacy ratio confirmed the economic efficacy of this group of drugs.

PMID- 9770813
TI  - [Glycopeptides (vancomycin, teicoplanin)--their place in the antibacterial
      therapy of patients in a high-risk group].
AB  - Today, when the number of high-risk patients is increasing, special attention
      should be paid to polyresistant gram-positive microorganisms staphylococci and
      enterococci, whose role in infective complications and septic states is
      increasing. The author analyzes published reports on the rate of isolation of
      methicillin-resistant staphylococci (MRS) and enterococci in different countries
      and relationship of this parameter with antibiotic policy. Special attention is
      paid to unjustified wide use of third-generation cephalosporines and their role
      in selection of polyresistant bacteria. The rate of MRS isolation vs. all other
      staphylococci at intensive care wards for newborns is as high as 63.9%. The
      incidence of coagulase-negative staphylococci (most often S. epidermidis) in
      clinical material (blood, cerebrospinal fluid, urine) from high-risk patients
      increased 2-3 times during two recent years. Glycopeptides vancomycin and
      teicoplanine are drugs of choice for the treatment of infections caused by such
      microorganisms (sepsis, endocarditis, osteomyelitis, pneumonia, etc.). These
      drugs should be listed among obligatory antibiotics for resuscitation and
      intensive care wards as life-saving drugs.

PMID- 9770814
TI  - [Specific antimicrobial immunity in patients with suppurative soft-tissue
      diseases undergoing conventional and modified ultraviolet irradiation of
      autologous blood].
AB  - Study of titers of specific antibacterial antibodies in the plasma by passive
      hemagglutination test and of the number of antibody-producing cells (APC) by
      local hemolysis test in patients with purulent diseases of soft tissues showed
      that both values increased after UV exposure of autoblood. This increase was more
      expressed after differentiated exposure of erythrocytic and leukocytic mass than
      after common UV exposure, which is explained by more complete exposure of
      leukocytes participating in immunological reactions. Study of APC during a UV
      session showed an increase in the count of these cells 6-8 h after exposure.

PMID- 9770815
TI  - [The rapid diagnosis of the toxicity of biological media in surgical patients].
AB  - A simple and objective rapid method for assessing serum and plasma toxicity is
      proposed, based on registration of the frog cardiac contractions. The method
      permits assessment of disease severity and monitoring the time course of
      pathological process after surgery and plasmapheresis. The level of toxemia and
      disease severity did not correlate in 20% of cases. Causes of this disagreement
      are discussed.

PMID- 9770816
TI  - [The use of a pressure-support ventilation regimen in the recovery of spontaneous
      respiration after heart operations].
AB  - Pressure-support ventilation (PSV) with supporting pressure (SP) levels 20, 15,
      13, 10, and 8 mm H2O was used in 111 patients with congenital heart disease after
      open-heart surgery during transfer to spontaneous respiration. PSV was associated
      with a significant decrease of respiratory rate and increase of respiratory
      volume (RV) at high SP levels. Respiration in the PSV mode permits the patient to
      control the inspiration flow, duration of inspiration phase, and RV, thus
      improving the patient-device synchronization. Cardiac index (CI) was changing
      with decrease of SP from 20-15 to 13 mm H2O in patients with different diseases
      during high SP PSV. This is caused by changed pulmonary circulation (transfer to
      intraacinar type) which increased the negative correlation between CI and chosen
      SP. In addition, CI depends not only on RV, but on the status of lung parenchyma
      as well.

PMID- 9770817
TI  - [A trial of the use of the Russian surfactant Surfactant HL for treating the
      respiratory distress syndrome in newborn infants].
AB  - HL surfactant was used for vital indications in 12 newborns with respiratory
      distress syndrome born at 28-36 weeks weighing 1000-2500 g at birth and
      postgestation age of up to 48 h, without apparent congenital diseases and evident
      signs of intrauterine infection and with intraventricular hemorrhages no more
      severe than of the second degree. Control group consisted of 12 babies with
      similar condition treated similarly but without surfactant. Surfactant HL was
      administered endotracheally in a dose of 50 mg/kg twice at 12-h interval. Good
      effect was attained in 4 newborns, stable deterioration in 2, and no effect in 6
      children. The majority of artificial ventilation values were virtually the same
      in both groups, but 2 days after surfactant, FiO2 was significantly lower in the
      controls than in experimental group (0.37 +/- 0.05 vs. 0.64 +/- 0.4, p < 0.01),
      and VEI was higher in the controls (0.33 +/- 0.05 vs. 0.18 +/- 0.03, p < 0.05).
      VR, MAP, FiO2, and oxygenation index decreased slower in the test group than in
      the controls. The mean duration of treatment with hypoxic gaseous mixtures and
      artificial ventilation of the lungs in the test vs. control group were 143 +/- 60
      and 288 +/- 45 h vs. 45.5 +/- 8.3 and 200.8 +/- 28.5 h, respectively. The
      incidence of air leakage syndrome was 83% (10 cases) in the test group and 17% (2
      cases) in the control group, chronic pulmonary diseases developed in 3 (25%)
      babies in the test and in 1 (8.3%) in the control group. Seven (67%) children in
      the test group developed obstructive changes in the lungs vs. 1 child in the
      control group. One child (test group) died from causes other than pulmonary.
      Hospital stay was longer in the test group than in control (14.8 +/- 1.7 vs. 8.3
      +/- 1.3 days, p < 0.01).

PMID- 9770819
TI  - [Cerebral oximetry in the para-infrared range. The possibilities for its use in a
      neurological resuscitation department].
AB  - The potentialities of cerebral oximetry in the para-infrared band as a means of
      neuromonitoring are assessed. The method is highly informative for selecting the
      treatment strategy during the acute period of craniocerebral injury and
      cerebrovascular diseases. Simultaneous analysis of intracranial pressure, central
      hemodynamics, and cerebral oximetry permits differentiation of mechanisms of
      intracranial hypertension and its compensation. Increase of rSO2 in increased
      intracranial pressure corresponds to brain hyperemia, its decrease to cerebral
      ischemia. A long trend of rSO2 changes is informative for disease prediction.

PMID- 9770818
TI  - [The use of propofol (Diprivan) for inducing anesthesia in neurosurgical
      patients. II. Its effect on intracranial pressure and on cerebral perfusion
      pressure].
AB  - Clinical study of the effect of propofol (diprivan) on intracranial and cerebral
      perfusion pressure (ICP and CPP, respectively) in 30 patients with neurosurgical
      diseases of the brain showed that propofol without narcotic analgesics did not
      block ICP increase in response to tracheal intubation. If it was combined with
      narcotic analgesics, the optimal combination was with pyritramide in a dose of
      0.4 mg/kg, because this combination blocked ICP increase in response to
      laryngoscopy and tracheal intubation and did not appreciably decrease CPP.
      Propofol for decreasing acute intracranial hypertension (like bolus injection of
      thiopental) during surgery is unjustified, because during anesthesia, bolus
      injection of propofol just negligibly decreases ICP.

PMID- 9770820
TI  - [Experience in using plasmapheresis as a component in the intensive therapy of
      critical states].
AB  - Ninety-six plasmapheresis sessions were carried out in 54 patients. The
      indications to the treatment were the DIC syndrome, positional compression
      syndrome, pancreonecrosis, acute poisonings, acute hepatic failure, sepsis, and
      immunocomplex diseases. The volume of plasma removed during a session was 300
      1500 ml. 50-60% of removed volume was replaced by fresh-frozen plasma and albumen
      and 40% with colloids.

PMID- 9770821
TI  - [The use of therapeutic plasmapheresis in the combined therapy of a female
      patient with idiopathic hemochromatosis].
AB  - A patient with idiopathic hemochromatosis has been followed-up for a long time.
      Methods decreasing serum iron content were used in succession. Five courses of
      plasmapheresis were administered. The level of serum iron normalized after each
      course consisting of 3-4 sessions, but the effect was but short-termed. Stable
      remission could be attained by maintenance desferal therapy after a course of
      therapeutic plasmapheresis, which can be regarded as a stage in basic therapy for
      idiopathic hemochromatosis.

PMID- 9770822
TI  - [The evaluation of the efficacy of preventing postoperative pancreatitis in
      stomach cancer patients by using izoptin and a prolonged peridural lidocaine
      block].
AB  - Efficacy of postoperative pancreatitis prevention is assessed in 123 patients
      with gastric cancer. Pancreatic bloodflow and central hemodynamics were assessed
      by rheography, activities of serum amylase and free-radical oxidation by
      biochemiluminescence of blood plasma. After radical surgery on the stomach,
      disorders of hemocirculation develop in the pancreas, leading to ischemia of the
      organ and formation of venous congestion; free-radical oxidation is activated and
      fermenturia increases. Prolonged epidural blocking with lidocaine prevented a
      decrease of arterial inflow to the pancreas, decreased the intensity of free
      radical oxidation, and was more effective than isoptin therapy.

PMID- 9770823
TI  - [Current trends in the development of monitoring observation in a resuscitation
      and intensive therapy department].

PMID- 9770824
TI  - [The endotracheal tube used during artificial pulmonary ventilation].
AB  - Tulepov's endotracheal tube, patent No. 2594, 1995, is described. The tube is
      used in all interventions under endotracheal narcosis and can be used for
      fibrobronchoscopy under narcosis. Bronchological manipulations under total
      narcosis were carried out using the proposed endotracheal tube in 76 patients
      with lung cancer.

PMID- 9770825
TI  - [Sepsis and the systemic inflammatory response syndrome].

PMID- 9770827
TI  - Failure of endoscopy disinfection in St George's Hospital, Tooting.

PMID- 9770826
TI  - [Accidental intraoperative whole-body hypothermia: the mechanisms of its
      occurrence and of self-warming].

PMID- 9770828
TI  - Prophylaxis for holiday contacts of single cases of meningococcal disease.

PMID- 9770829
TI  - AIDS and HIV infection in the United Kingdom: monthly report.

PMID- 9770830
TI  - Notes from a clinical information system project manager requisite survival
      skills.

PMID- 9770831
TI  - Preparation for an online asynchronous university doctoral course. Lessons
      learned.
AB  - This article addresses the development of the initial course in the first
      completely online doctoral program in nursing. Synchronous and asynchronous
      methods of distance education were assessed. Planning focused at the university,
      school, and course levels. University planning involved the technical
      infrastructure, registration, student services, and library services. School
      planning examined administrative commitment and faculty commitment and
      willingness. Course planning focused on marketing, precourse information, time
      frame, modular design, planned interaction, and professor availability and
      support. Implementation issues centered on getting students connected, learning
      the software, changing instructional methods, and managing chats. Traditional
      methods of evaluating student learning and course evaluation were supplemented
      with the development of qualitative and quantitative tools to gather data for
      making administrative decisions. The Dean and faculty agreed that the internet
      was an effective method of delivering content in the initial Health Policy
      course. The Dean and faculty agreed to continue the PhD program online for one
      cohort and continue to evaluate student progress and faculty and student
      satisfaction.

PMID- 9770832
TI  - From computer technology to information technology. Findings from a national
      study of nursing education.
AB  - A research survey was conducted on a stratified random sample of National League
      for Nursing accredited diploma, associate, baccalaureate, and master programs to
      determine the status of computer and information technology in nursing education.
      Fifty-five percent (n = 190) of the 347 selected schools responded. Compared with
      national statistics, all programs (diploma, associate, and higher degree) were
      proportionately represented. Findings indicated that schools have almost
      universal access to computers and educational software. However, further data
      analysis indicated that a majority of schools lacked a coordinated plan for
      technology implementation and were underfinanced for technology and related
      personnel. In addition, less than one third of the schools addressed nursing
      informatics (the information of nursing) in the curriculum and only 19 schools
      indicated that nursing informatics was offered as a separate course. Successful
      strategies for the implementation of computer and information technology are
      presented based on the findings.

PMID- 9770833
TI  - Opening minds. Values clarification via electronic meetings.
AB  - Values clarification for nursing practice is one of the most challenging aspects
      of nursing education. Use of electronic meeting software has been demonstrated to
      be effective in overcoming typical barriers to student growth. Inhibitions
      related to fear of censorship are overcome by anonymity of the system.
      Monopolizing by dominant members is controlled when the ability to speak in
      parallel exists. Overall, this application of electronic meeting software in the
      classroom demonstrated involvement of all students in an innovative approach to
      understand the effect of personal values on health policy development in a
      graduate nursing course.

PMID- 9770834
TI  - Computerized documentation for a rural nursing intervention project.
AB  - The Rural Partnership Linkage for Cancer Care project is a program of advanced
      practice nursing care made available to rural cancer patients to provide
      education, symptom management, referral, and support within their communities.
      The advanced practice nurses used a computerized clinical information system
      (CCIS) to record care. In this article the CCIS is described, the software and
      hardware requirements are discussed, and the outcomes and value of the system are
      discussed. The CCIS is a relational database run on laptop computers that
      includes screens for standard recording of demographics, physical exam, symptoms,
      and treatments. The advanced practice nurses track patient symptoms over time,
      noting which treatments are successful in resolving or reducing the problems.
      Information from patient visits is selected by help menus for inclusion into
      referral forms, reports of patient care, and discharge summaries. Reports can be
      faxed or mailed to distant sites. The research team uses the combined data set to
      examine symptom patterns, nursing diagnosis, and treatments that result in
      improved physical and psychological functioning and symptom resolution. Rural
      cancer patients and their families benefit from care management, participation in
      research, and communication of patient health status in an integrated and timely
      fashion made possible by the CCIS.

PMID- 9770835
TI  - [Obituary to Professor, medical doctor Ireneusz Roszkowki].

PMID- 9770836
TI  - [Factor VIII inhibitor appearing in women during delivery].
AB  - Factor VIII inhibitor is rare, but very serious postpartum complication. Bleeding
      diathesis caused by this inhibitor is called acquired haemophilia. Three women
      with postpartum inhibitor to factor VIII and life threatening bleeding were
      described. In two patients bleeding was controlled by treatment with high doses
      of human and porcine factor VIII concentrates. One patient died presenting
      uncontrolled haemorrhagic diathesis. This work presents the problems of the
      diagnosis, treatment and also the elimination of the factor VIII inhibitor.

PMID- 9770838
TI  - [Risks for atherosclerosis in post-menopausal women and in women with hormonal
      replacement therapy].
AB  - The aim of our study was the evaluation of atherogenesis in postmenopausal women
      and after HRT in correlation with BMI, IGF-I and lipid profile. We have found
      unfavourable changes in lipid profile in positive correlation with BMI, after
      three months treatment we have found decrease in concentration of total
      cholesterol and LDL cholesterol between women with proper BMI.

PMID- 9770837
TI  - [Monitoring oxypurines levels in women with pregnancy induced hypertension and in
      women with physiological pregnancy].
AB  - In this paper the concentration of oxypurines in the plasma taken from women with
      PIH, regular pregnancies and control group was determined. In comparison to the
      other groups very high concentration of HX and low X in the plasma of women with
      PIH was found. Such a result allows for the conclusion proving the exsistance of
      hypoxia in the group of women with PIH. To confirm the claim the clinical
      evaluation of pregnant women, fetuses and newborns was used. The values of most
      parameters proved that fetuses and newborns coming from the pregnancies of women
      with complicated PIH are weak, in the clinical evaluation, than those coming from
      the regular pregnancies.

PMID- 9770839
TI  - [Laparoscopic image of pelvic minor organs in women after ovary surgery].
AB  - An analysis of indications to laparoscopy and an evaluation of the abdominal
      cavity organs in patients who earlier in their history have undergone laparotomy,
      is the object of this report. A group of 86 patients was studied and in all cases
      laparoscopy followed previous laparotomy. Infertility, PPS, and pelvic mass were
      found to be the most frequent indications to laparoscopy. In 74.4% of patients
      who had laparotomy in their history, our laparoscopy revealed pelvic adhesions
      and in 9.3% of patients--endometriosis. Laparoscopy constitutes safe diagnostic
      and therapeutic procedure, complications occurred in 2.3% of patients.

PMID- 9770840
TI  - [Surgical treatment of uterine myoma: need for surgery and long-term results].
AB  - We analysed the indications to myomectomy in females in reproductive age and
      estimated efficasy of this treatment. 112 patients aged 23-45 were analysed. Most
      common indication to this procedure were: menorrhagia--45.54%, myoma found at
      gynecological examination--21.43%, adnexal mass--20.54% and pelvic pain--15.18%.
      54.46% patients were parous, 34.82% nulligravid and 10.72% had a history of
      spontaneous abortion. There was low percentage of intraoperation complications-
      2.67%, as well as postoperation complications--3.57%. More than 5 years follow-up
      revealed recurrent myoma in 14.28% females and in 6.25% hysterectomy was
      performed. Cervical polypus was found in 8.04%, endometrial hyperplasia in 2.68%.
      18.75% patients had menorrhagia and 5.36% abdominal pain. Successful pregnancies
      have occurred in 42.11% infertile women prior to surgery but with patent
      fallopian tubes. Our study shows that myomectomy is safe and well accepted method
      of treatment for uterine myomas however always stands a risk of recurrents.

PMID- 9770841
TI  - [The preliminary evaluation of the value of interstitial brachytherapy combined
      with external irradiation in the treatment of advanced vulvar cancer].
AB  - Results of treatment of 10 patients with local-regionally advanced vulvar cancer
      are described. Loco-regional control of tumor was achieved in 6 patients. These
      patients remain disease-free with follow-up from 18 till 36 months. The procedure
      was well tolerated with low serious toxicity rate.

PMID- 9770842
TI  - [Biochemical and endocrinological analysis of breast cyst fluid].
AB  - The gross cystic disease (breast cyst < 3 mm in diameter) is common benign
      disease of the breast. The relations GCD with breast cancer remain the
      fundamental problem. Although the cysts itself only exceptionaly degenerates into
      cancer, the presents of macrocystic disease multiplies by 3 to 4 the risk of
      cancer. A lot of interesting examinations were performed on cyst fluids aspirated
      from patients to identify women with benign breast disease and particular risk
      for breast cancer. There are two groups of breast cysts: these lined by apocrine
      epithelium and those lined by flattened epithelium. It is generally accepted that
      measurement of intracystic [Na+]/[K+] is a simple way of differentiating between
      these two groups of cysts. Higher intracystic concentrations of same substances
      may provide an explanation for the higher risk of breast cancer, which has been
      observed in low electrolyte group. Breast cyst fluid samples were analyzed for a
      lot of hormones, proteins, specific growth factors, adhesion molecules, bile
      acids, tumor markers and their levels were compared with breast cancer risk. At
      the present time, the biochemical measurements in cyst fluids aren't popular to
      identify women likely to develop breast cancer. We should use other diagnostic
      methods to examine these patients.

PMID- 9770843
TI  - [A case of true hermaphroditism].
AB  - In the paper we present the case of true hermaphroditism in young girl. The
      examinations revealed the presence of an ovary with left corn of the uterus at
      the left side and immature testis with seminal duct the right side.

PMID- 9770844
TI  - [Sarcoidosis in the scar after a perineal surgery].
AB  - An infiltration in the perineal scar occurred in a 34 years old patient six
      months after colpomyoperineoplasty. This infiltration which turned out to be a
      focus of sarcoidosis. The patient was treated pharmacologically. The lung and
      local symptoms regressed.

PMID- 9770845
TI  - [Activity of tissue inhibitors of metal proteinases (TMI) in th fetal membrane
      during term vaginal delivery].
AB  - In the foetal membranes that ruptured spontaneously or by means of amniotomy
      during term vaginal deliveries the activity of tissue inhibitors of
      metalloproteinases was evaluated. Samples were taken from the proximity of the
      rupture line. Almost twofold lower TIMPs activity in the naturally ruptured
      membranes was observed. We conclude that during normally proceeding term vaginal
      delivery the activity of TIMPs in the lowermost pole of the amniotic sac is
      decreased, what may play very important role in the mechanism of the term rupture
      of the foetal membranes.

PMID- 9770846
TI  - [Acid-base balance and activity of CK, ALT, GPT, LDH enzymes in umbilical venous
      flood in full-term infants].
AB  - Examinations of acid-base balance and activity of CK, GOT, GPT, LDH enzymes were
      performed in 32 full-term neonates after delivery. Statistical dependence was
      stated between GOT (p = 0.012) and LDH (p = 0.00012) activities and pH of
      umbilical venous blood. Statistical dependence was also stated between GOT and
      LDH activities and HCO3 and BE (p = 0.0008). Elevated values of GOT and LDH might
      indicate past fetal asphyxia.

PMID- 9770847
TI  - [Elective premature delivery: clinical studies].
AB  - Cases of placental dysfunction complicated additionally by premature delivery
      were assessed. Abnormalities of pregnancy leading to chronic deficit in
      oxygenation were analyzed. Clinical utility of diagnostic procedures was
      evaluated. Neonatal condition in cases of elective premature birth versus
      spontaneous preterm delivery was compared.

PMID- 9770848
TI  - [Spinal analgesia and perioperative low molecular weight heparin (LMWH)
      prophylaxis of thrombosis. Safety aspect].
AB  - For many gynecological surgery patients belonging to deep vein thrombosis (DVT)
      high-risk group the analgesia of choice is regional spinal analgesia.
      Perioperatively LMWH--Fraxiparine was administered to 426 gynecological surgery
      patients and to 113 caesarean section patients. The first dose 7500 ICU s.c. was
      administered 2 hours before operation and consecutive ones every 24 hours for 5
      to 7 days. The drug didn't cause any anaesthesia complications like enhanced
      bleeding after lumbar punction. It was emphasised in the discussion that in
      choosing this kind of prophylaxis certain conditions should be fulfilled in order
      to avoid spinal hematoma.

PMID- 9770849
TI  - [The evaluation of endometrial invasion of cervical Ib grade carcinoma].
AB  - Depth and extension of infiltration into uterine corpus with regard to 5 years
      survival in 33 patients in which Wertheim-Meigs surgery was done due to cervical
      cancer stage Ib is estimated in this paper. Endometrial stromal invasion or depth
      invasion less than 1/2 of myometrium at the site of internal ostium were of
      similar (91.7% > 5 years survival time) as an invasion confined solely to uterine
      cervix (86.9% > 5 years survival). Invasion of more than 1/2 of myometrium was
      associated with poor prognosis (46.7% 5-years survival). Bad prognosis (16.6% 5
      year survival time) in patients with deep and extensive of uterine corpus and
      fundus should be tied to massive infiltration increased hematogenous and
      lymphatic dissemination. None of patients with deep and extensive invasion, lymph
      nodes metastases and uterine vasa embolies did survive 5 years period of time.
      These patients need individual postoperative adjuvant therapy.

PMID- 9770850
TI  - [Vascular invasion and prognostic factors in cervical Ib grade cancer without
      metastases in lymph nodes].
AB  - We were looking for presence, severity and extension of the invasion of vessels,
      with regard to the prognosis in 275 patient with infiltration limited only to
      uterine cervix (Ib), in which Wertheim-Meigs surgery was performed. It was found
      invasion of many vessels- in outside of the cervix is associated with poor
      prognosis, no matter weather the local lymph nodes are metastatic or not and no
      matter what the size of the neoplastic infiltration is. Patient with severe and
      extensive vascular invasion require further postoperative treatment.

PMID- 9770851
TI  - [Nipple dysplasia and androgen syndrome].
AB  - Among 1500 patients in the reproductive age of Clinical Department of
      Endocrinological Gynecology in State Hospital in Warszawa, Poland estimated the
      correlations between the onset of benign breast disease (BBD) and the incidence
      of androgenic syndrome. Symptoms of the androgenic syndrome stated in cases of
      191 women; 51 of them had also benign lesions of the breasts. It makes 26.9
      percent women with the symptoms of androgenicity. Clinical studies have
      correlated mean age patients with acne, hirsutism, menstrual cycle disturbances,
      gain of weight (androgenic syndrome) and mean age women who have suffered both
      androgenicity and BBD.

PMID- 9770852
TI  - [Chromosomal abnormalities in male gametes].
AB  - Most of the human chromosomal abnormalities seems to be of a germ-cell origin.
      Human oocytes are difficult to obtain and to handle, so most of the studies has
      been performed on male gametes. Genetic status of spermatozoa may be critical for
      human reproduction as well as wellbeing of fetus. The ability to identify and to
      characterize chromosomal aberrations in human sperm would lead to understanding
      of the mechanism causing chromosomal abnormalities and to approach possible
      preventive strategies. The aim of this paper was to present current data
      concerning the chromosomal aberations in human spermatozoa. Presented overview
      strongly underlines the importance of genetic investigations of male gametes.

PMID- 9770853
TI  - [Steps in the treatment of ovarian cancer].
AB  - The paclitaxel/cisplatin regimen is superior to standard therapy PC based on
      higher overall response rates, higher negative second-look laparotomy rate and
      overall survival. The regimen paclitaxel/cisplatin/cyclophosphamide seem to give
      the best treatment results. Interval debulking surgery after initial laparotomy
      and intraperitoneal therapy with cisplatin and i.v. cyclophosphamide in patients
      with residual disease improve overall survival rate.

PMID- 9770854
TI  - [Hormonal aspects of nipple cancer].
AB  - A substantial body of experimental, clinical and epidemiological evidence
      indicates that hormones play a major role in the aetiology of breast cancer. The
      role of endogenous and exogenous hormones in the development of breast cancer is
      discussed. The oestrogen's molecular mechanism of influence on breast cancer
      cells and hormonal drugs are presented. Combined analysis of currently available
      studies shows, that breast cancer risk is not increased with the use of oral
      contraceptives (with the exception for the young women using them for more than
      10 years). In healthy postmenopausal women the benefits associated with hormone
      replacement therapy can outweigh the risk of developing of breast cancer. The
      overall risk and benefits of hormone replacement therapy among breast cancer
      survivors remain uncertain and it's prescription should be undertaken cautiously.

PMID- 9770855
TI  - [Fetal bladder ectasia as an obstacle to pre-term labor].
AB  - Paper describes a case of fetal urine bladder ectasia in 27th week of gestational
      age. Large diameter of ectasia was a need for operative delivery.

PMID- 9770856
TI  - [Ligation of iliac internal arteries in advanced endometrial cancer].

PMID- 9770857
TI  - [A rare case of ovarian leiomyoma. A case report with review of literature].
AB  - We report an exceptional case of ovarian leiomyoma in 73 years old patient.
      Leiomyoma of the ovary is a very rare tumor. Most cases are asymptomatic, this
      benign neoplasm is usually found incidentally on routine pelvic examination, at
      surgery or at autopsy. The available literature is reviewed. The possible
      histogenesis of ovarian leiomyoma was discussed.

PMID- 9770858
TI  - Opioid receptor mediated anticonvulsant effect of pentazocine.
AB  - Intraperitoneal (i.p.) administration of (+/-) pentazocine (10, 30 & 50 mg/kg), a
      Sigma opioid agonist, resulted in a dose dependent anticonvulsant action against
      maximal electroshock seizures in mice. This anticonvulsant effect of pentazocine
      was not antagonized by both the doses of naloxone (1 and 10 mg/kg) suggesting
      thereby that its anticonvulsant action is probably mediated by Sigma opiate
      binding sites. Its anticonvulsant effect was potentiated by both the
      anticonvulsant drugs viz. diazepam and diphenylhydantoin. Morphine, mu opioid
      agonist, on the other hand, failed to protect the animals against maximal
      electroshock seizures when it was given in doses of 10-40 mg/kg body wt.

PMID- 9770859
TI  - Research skills acquisition by interns: a case study.
AB  - This study shows the impact of a holistic structured training programme on the
      acquisition of research skills by a batch of 13 interns of Pramukhswami Medical
      College, Gujarat, India, commensurate with their envisaged roles according to the
      concept of "Essential National Health Research" (ENHR). There was a significant
      improvement in the knowledge scores of the participants, subsequent to the
      training programme, as evidenced by an improvement over their mean pretest score
      of 16.4 +/- 11.0 to a posttest score of 87.1 +/- 19.9. The study also discussions
      the suggestions and feedback of the participants about the programme.

PMID- 9770860
TI  - Chemical analysis of urinary calculi in Haryana.
AB  - Quantitative chemical analysis of 225 urinary calculi (128 Renal, 57 bladder and
      40 ureter) collected from hospitals of different districts of Haryana was carried
      out. CaOxM was found to be present as a major component in all the stones
      analysed, while MAP, HA, CA and UA were found in 83.7%, 83.6%, 13% and 78.9%
      cases, respectively. The content of CaOxM was found to be higher in renal stones
      as compared to ureter and bladder stones, while the concentration of MAP was
      higher in bladder stones as compared to kidney and ureter stones. HA content was
      higher in ureter and UA was higher in bladder stones as compared to other urinary
      stones.

PMID- 9770861
TI  - Rapidly progressive polyostotic eosinophilic granuloma involving spine: a case
      report.
AB  - 17 yrs. old boy presented with low back pain and progressive deformity with no
      history of trauma or tuberculosis. Clinically there was tender knuckle formation
      at L2 level. X-rays showed vertebra plana (concentric collapse) at L2 level along
      with skull involvement. While being investigated patient developed partial
      collapse at L3 level and pelvis involvement within a week. On biopsy from L3
      vertebra the lesion was found to be eosinophilic granuloma. This is a case report
      of a rare instance in which acute progression of eosinophilic granuloma occurred
      involving multiple skeletal sites in an adult.

PMID- 9770862
TI  - Dhat syndrome--culture bound sex neurosis.

PMID- 9770863
TI  - Risk factors for coronary heart disease in Asian Indians: clinical implications
      for prevention of coronary heart disease.
AB  - Contrary to popular belief that coronary heart disease (CHD) is uncommon in
      developing countries, Asian Indians have among the highest prevalence of CHD.
      Analysis of numerous studies have now revealed that the usual risk factors i.e.
      hypertension, hypercholesterolemia, obesity, smoking and a family history of CHD,
      are not common among South Asians. Rather, they possess a different risk factor
      profile characterized by high triglycerides, low HDL, glucose intolerance,
      insulin resistance, abdominal obesity and increased lipoprotein(a) levels. On
      account of this difference and the alarming explosion of CHD in India, guidelines
      for prevention of CHD as laid down by the American Heart Association may not be
      applicable in our population. A judicious diet incorporating commonly used Indian
      food items and regular exercise will go a long way in effective primary
      prevention.

PMID- 9770864
TI  - Prevention of gastrointestinal diseases.

PMID- 9770865
TI  - Prevention of respiratory diseases.

PMID- 9770866
TI  - Prevention of genetic disorders.

PMID- 9770867
TI  - Ayurveda's role in preventing disease.
AB  - Modern medical science is currently in the throes of a revolution which is likely
      to have a dramatic impact on both the theory of medicine and the way it is
      practised. The mechanistic model which served biomedicine well for many years is
      gradually collapsing, thanks to the efforts of dedicated researchers who have
      looked beyond that model's flaws. Thus we now know that networks of chemical
      communication exist between the nervous and immune systems, and that prayer at a
      distance can positively affect the conditions of those who are seriously ill,
      even when the prayer and the patient are not known to one another. Another
      participant in this exciting climate of change and ferment is Ayurveda, India's
      ancient medical system. While Ayurveda has already contributed much to modern
      medicine (reserpine, gugulipid, plastic surgery), its real contributions are yet
      to be made. While some of these are likely to come in matters of materia medica
      and technique, most will likely be derived from Ayurveda's way of seeing the
      world, its "darshana." This paper outlines a few of the ways in which Ayurveda's
      "vision" is likely to facilitate medicine's ability to teach people not just how
      to avoid disease but how to proactively develop and maintain a healthy "state."

PMID- 9770868
TI  - Micronutrients in disease prevention.

PMID- 9770869
TI  - A blueprint for cancer cure.

PMID- 9770870
TI  - A new combination contraceptive launched.

PMID- 9770871
TI  - Prevention of ocular diseases.

PMID- 9770872
TI  - Prevention & management of stroke.

PMID- 9770873
TI  - Cancer prevention.

PMID- 9770874
TI  - Meditation for prevention of disease.

PMID- 9770875
TI  - Prevention of diseases an Ayurvedic approach.

PMID- 9770876
TI  - New vaccines for disease prevention.
AB  - New vaccines are needed for the control of some existing as well as other new or
      emerging diseases. In the long run they can be made cost-effective with the
      application of modern methods of biotechnology and would thus save considerable
      expense and hardship suffered at present by mankind.

PMID- 9770877
TI  - Influence of Coccinia indica on certain enzymes in glycolytic and lipolytic
      pathway in human diabetes.
AB  - Dried extract of C Indica in doses of 500 mgm/kg body weight were administered
      orally to 30 diabetic patients for six weeks. Blood samples were collected 15
      minutes after administration of 10 IU heparin for estimation of LPL, before and
      after treatment with C. Indica Non heparinised samples were utilized for
      estimation for G-6-p (ase), LDH and blood sugar. Severity of disease were
      assessed by the findings of blood sugar level. Mild diabetes had no effect on
      LPL, LDH and G-6-P (ase). But, reduced activity of enzyme LPL and raised level of
      G-6-P (ase) and LDH in plasma of severe diabetics were found to be highly
      significant (p < 0.001). The alteration in these parameters in untreated
      diabetics were restored after treatment with C. indica Hence, it can be
      postulated that the ingredients present in the extract of C. indica, act like
      insulin, correcting the elevated enzymes G-6-p (ase), LDH in glycolytic pathway
      and restore the LPL activity in lypolytic pathway with the control of
      hyperglycemia in diabetes.

PMID- 9770878
TI  - Parity as a risk factor for cancer cervix.
AB  - The present hospital based, group matched case control study was carried out at
      Gynecology Clinic, Govt. Medical College hospital, Nagpur, to investigate role of
      parity in the outcome of cancer cervix. The study included 230 cases of cancer
      cervix and equal number of controls, matched for age. The study identified
      significance of multiparity, as a risk factor for cancer cervix. Estimates of
      attributable risk proportion (ARP) and population attributable risk proportion
      (PARP) endorsed etiological and preventable role of multiparity in the outcome of
      cervical cancer, respectively.

PMID- 9770879
TI  - Ethnopharmacology and some traditional medical practices--Part I.

PMID- 9770880
TI  - Disaster management knowledge attitude & practice of urban slum dwellers.
AB  - A KAP study was done in the area of Disaster Management in urban slums of Pune
      City. The Youth Organisations' members and the members of Mahila Mandals were the
      study subjects. It was found that there was marked improvement in the knowledge
      and attitudes of these subjects towards disasters. It is recommended that members
      of Mahila Mandals and members of Youth Organisations can act as 'frontline
      workers' in the situations of disasters after imparting some training in disaster
      management.

PMID- 9770881
TI  - Cerebral dysfunction in vivax malaria: a case report.
AB  - A case of vivax malaria with neurological symptoms is described.

PMID- 9770882
TI  - Response of colony stimulating factor in cancer chemotherapy induced
      myelosuppression--a case report.

PMID- 9770884
TI  - India's polio eradication efforts at cross roads.

PMID- 9770883
TI  - Typhoid fever--an update.

PMID- 9770885
TI  - Sensitivity of poliomyelitis surveillance in India.
AB  - OBJECTIVE: To estimate the sensitivity of poliomyelitis surveillance in India.
      DESIGN: A comparison of two sets of data obtained from lameness surveys and
      routine surveillance system. METHODS: Lameness surveys were undertaken by the
      Ministry of Health and Family Welfare in 1981, 1989 and 1992 using 30-cluster
      sampling technique. These data were compared with the number of polio cases
      reported through routine surveillance system. RESULTS: Based on the 1981 survey
      which was undertaken near the initiation of routine immunization with oral polio
      vaccine (OPV) in India, poliomyelitis incidence was estimated at 25 cases per
      100,000 population. Subsequent studies in 1989 and 1992 estimated a decrease in
      incidence rates to 15.7 and 6.3 cases per 100,000 population, respectively.
      Comparing the number of reported cases with the survey estimates provided a
      measure of the sensitivity of (completeness of reporting) surveillance; the
      sensitivity increased from 8% in 1981, to 20% in 1989, to 32% in 1992.
      CONCLUSION: The results are encouraging when compared with the global estimates
      of 10% reporting in 1993. Nevertheless, there is a need for further improvement
      in the completeness of reporting of poliomyelitis cases to detect all the cases
      of acute flaccid paralysis to allow epidemiological investigations and effective
      follow-up action which is critical to interrupt wild virus transmission.

PMID- 9770886
TI  - Persistent hyperinsulinemic hypoglycemia of infancy.
AB  - OBJECTIVE: To study the nature and clinical course of persistent hyperinsulinemic
      hypoglycemia of infancy (PHHI) due to nesidioblastosis. DESIGN: Clinical,
      laboratory and therapeutic evaluation of infants with this disorder and study the
      outcome. SETTING: Hospital born neonates and infants referred from other
      hospitals. SUBJECTS: Thirteen infants from 9 families inclusive of four pairs of
      siblings referred within few hours of birth to 3 months of age, for seizures.
      Mean birth weight was 3.68 +/- 0.45 kg. Consanguinity documented in one sporadic
      and one familial case. METHODS: Clinical and laboratory evaluation by standard
      biochemical and radioimmunoassay techniques. RESULTS: The mean serum insulin
      level of 24.2 +/- 12.5 mIU/ml was in the normal range but inappropriately high
      for the corresponding hypoglycemic blood sugar (23.1 +/- 9.1 mg/dl) value, with
      an I/G ratio of 1.36 +/- 0.97; as in hyperinsulinemia (normal < 0.4).
      Investigations excluded other causes of persistent hypoglycemia. A trial of
      i.v./oral glucose, frequent carbohydrate rich feeds in all, oral diazoxide (10 to
      20 mg/kg) in 9/13 cases along with subcutaneous octreotide (20 micrograms/kg QID)
      in one helped, but pancreatic resection (85 to 90%) was opted for in two (1
      familial, 1 sporadic). Six infants including one with pancreatic resection
      succumbed to hypoglycemia (n = 1) or fulminating infection (n = 3) or brain
      damage. Of the seven survivors, one familial case with pancreatic resection is
      brain damaged, and of the six on diazoxide therapy, one is slightly subnormal
      while one sporadic and three familial cases have done well. One infant was lost
      to follow up. Diazoxide could be withdrawn in two subjects (1 familial, 1
      sporadic) by 8 years of age signifying maturation of islet cell function.
      CONCLUSION: PHHI appropriately known as 'Islet cell dysmaturation syndrome' is a
      complex disorder posing problems in diagnosis and therapy. The high familial
      incidence (77%), with intrafamilial variation in the severity, insulin levels in
      the normal range but in appropriately high for the blood glucose levels, normal C
      peptide levels, with normal I/G ratio (< 0.4) in 4/13 are some of the notable
      features of this study. Severe recurrent infections in nearly 30%, is an unusual
      feature in this series and needs an indepth study. The mortality (46%) and
      morbidity (43%) in survivors is high and calls for greater awareness, early
      diagnosis and genetic counselling, as this disorder may be familial.

PMID- 9770887
TI  - Helicobacter pylori infection in recurrent abdominal pain.
AB  - OBJECTIVE: To study the relationship between Helicobacter pylori (Hp) infection
      and recurrent abdominal pain (RAP) and to evaluate various modalities to diagnose
      Hp infection. DESIGN: Prospective case control study. SETTING: Teaching hospital.
      METHODS: Children between 3-12 years of age with RAP in whom upper
      gastrointestinal endoscopic examination was indicated were studied. Endoscopic
      biopsy specimen were collected from duodenum, antrum and esophagus. Apart from
      histopathological examination of biopsy material, rapid urease test (RUT) of the
      antral biopsy specimen and blood examination to estimate specific IgG antibodies
      to Hp by Indirect Solid Phase Enzyme Immunoassay was performed. The results of Hp
      IgG antibodies was compared with age matched controls. RESULTS: Thirty one
      children with RAP were subjected to endoscopic examination and their anti Hp IgG
      antibodies status compared with 26 controls. Hp colonization was detected in 7
      children (23%) with RAP; by RUT in 23% and antral biopsy in 16% of cases. Anti Hp
      IgG antibodies were also positive in almost equal proportion (19%) of controls (p
      = 0.757). Endoscopic examination revealed esophagitis in 16% of cases and none
      had evidence of gastric or duodenal erosion, ulcer or cobblestone appearance of
      antrum. A significant correlation of Hp was noticed with chronic antral gastritis
      (p = 0.002), chronic duodenitis (p = 0.02) and age > 10 years (p = 0.02). No
      significant correlation was noticed between Hp colonization and various
      socioeconomic risk factors. CONCLUSION: Hp does not seem to be commonly
      associated with RAP in our patient population as Hp colonization was detected in
      only 23% of cases which was not significantly higher than the seroprevalence of
      anti Hp IgG antibodies in the controls. However, a small sample size of our study
      limits drawing any firm conclusions. Antral gastritis and chronic duodenitis had
      a significant correlation with Hp colonization. RUT was found to be a reliable
      diagnostic test to detect Hp.

PMID- 9770888
TI  - Subacute sclerosing panencephalitis.

PMID- 9770889
TI  - A suggested model for internal assessment as per MCI Guidelines on Graduate
      Medical Education, 1997. Medical Council of India.

PMID- 9770890
TI  - Intermittent positive pressure ventilation in a neonatal intensive care unit:
      Hyderabad experience.

PMID- 9770891
TI  - Clinical and biochemical asphyxia in meconium stained deliveries.

PMID- 9770892
TI  - Assessment of iodine deficiency in Pondicherry.

PMID- 9770893
TI  - Concurrent cryptococcal meningitis and falciparum malaria in a child with
      nephrotic syndrome.

PMID- 9770894
TI  - Intestinal lymphangiectasia.

PMID- 9770895
TI  - Arthritis in hypogammaglobulinemia.

PMID- 9770896
TI  - Ascaris lumbricoides: unusual exit.

PMID- 9770897
TI  - Exomphalos.

PMID- 9770898
TI  - Immunogenic response to hepatitis B vaccine in Indian infants.

PMID- 9770899
TI  - Painful pricks.

PMID- 9770900
TI  - Tobacco use in rural Indian children.

PMID- 9770901
TI  - Acute bacterial meningitis.

PMID- 9770902
TI  - Umbilical cord blood collection with an infant feeding tube.

PMID- 9770903
TI  - Colored and sweetened death trap?

PMID- 9770904
TI  - Needle length and injection technique for efficient intramuscular vaccine
      delivery.

PMID- 9770905
TI  - Furosemide in bronchial asthma.

PMID- 9770906
TI  - Cases of male babies with easy bruising of skin.

PMID- 9770907
TI  - Acquisition of derived nominals in Hebrew: developmental and linguistic
      principles.
AB  - Derived nominals are abstract nouns derived from verbs and adjectives by
      nominalization. This study traces the route taken by Hebrew-speaking children in
      the acquisition of Hebrew derived nominals (HDNs) of two types: action nominals
      which conform in structure to the small set of obligatory verb patterns
      (binyanim) (e.g., ktiva 'writing') and deverbal nouns, which belong to separate
      nominal patterns (e.g. maga 'touch'). One hundred native speakers of Hebrew
      (children aged 5, 8, 11 and 15, and adults) were tested on comprehension and
      production of HDNs. The test items were grouped by binyan patterns and by
      morphological regularity. Results showed that acquisition of HDNs starts at about
      age 8 and is not complete by age 15, and that task type, binyan pattern and
      morphological regularity all affect ease of acquisition. We consider the
      strategies employed in the course of acquisition of HDNs and offer an explanation
      for this late acquisition which requires a vast amount of prior integrated
      knowledge.

PMID- 9770908
TI  - Why is a pomegranate an apple? The role of shape, taxonomic relatedness, and
      prior lexical knowledge in children's overextensions of apple and dog.
AB  - Children's overextensions (e.g. referring to a pomegranate as apple) raise
      intriguing questions regarding early word meanings. Specifically, how do object
      shape, taxonomic relatedness, and prior lexical knowledge influence children's
      overextensions? The present study sheds new light on this issue by presenting
      items that disentangle the three factors of shape, taxonomic category, and prior
      lexical knowledge, and by using a novel comprehension task (the screened
      alternative task) in which children can indicate negative exemplars (e.g. which
      items are NOT apples). 49 subjects in three age groups participated (Ms = 2;0,
      2;6, and 4;5). Findings indicate: (1) Error patterns differed by task. In
      production, errors were overwhelmingly due to selecting items that matched the
      target word in BOTH shape and taxonomic relatedness. In comprehension, more
      errors were based on either shape alone or taxonomic relatedness alone, and the
      nature and frequency of the overextensions interacted with prior lexical
      knowledge. (2) Error patterns also differed markedly based on the word being
      tested (apple vs. dog), in both comprehension and production (3) As predicted,
      errors were more frequent in production than comprehension, though only for
      children in the two younger age groups. Altogether, the study indicates that
      overextensions are not simply production errors, and that both taxonomic
      relatedness and object shape play a powerful role in early naming errors.

PMID- 9770909
TI  - The acquisition of plural marking in English and German revisited: schemata
      versus rules.
AB  - This article contributes to a debate in the linguistic and psychological
      literature that centres around the representation of morphologically complex
      words in the grammar and in the lexicon. The issue is whether inflectional
      morphology is rule-based (i.e. symbolically represented), or whether the
      assumption of pattern association is more adequate to account for the facts. On
      the basis of the analysis of acquisitional data the article strongly argues for
      the latter alternative. In a classic experiment that helped shape the development
      of acquisition theory Berko (1958) reported substantial support for ITEM-AND
      PROCESS rules in the acquisition of plural morphology in English. A large part of
      her results were zero responses (repetition of the stimulus). A reinterpretation
      of these zero responses in light of schema theory and the cue strength hypothesis
      shows a striking departure from randomness. Berko's subjects tended to repeat
      stimuli just to the extent that these already resembled a plural schema. A
      reinterpretation of data reported in Innes (1974) achieved compatible results.
      This data set is far more extensive than Berko's and is used in the present study
      to put the schema model to a more stringent test. A reinterpretation of a
      parallel experiment with German children, using the cue strength analysis of the
      more complex plural morphology of German yielded parallel results. Finally,
      natural acquisitional data obtained from seven German speaking children aged
      between 2;1 and 2;9 are analysed. Again, strong support is found for the schema
      model. It is suggested that a schema-learning mechanism may underlie the
      acquisition of morphology, even when the end product of the learning process
      involves item-and-process rules, as in the case of English plural formation. In a
      schema-learning model, the child builds schematic representations for possible
      singular and plural lexical items as whole gestalts, and attempts to map concrete
      forms onto these schemata in deciding whether the forms have singular or plural
      value.

PMID- 9770910
TI  - Production, conceptualization and change in distinctive featural categories.
AB  - This study extends prior investigations of children's abilities to conceptualize
      distinctive phonological features in development. The purpose was to establish
      the relationship between a child's productive and conceptual knowledge, and to
      examine its potential influence on phonological change. Six children evidencing
      phonological disorders (aged 3;4 to 5;7) participated in evaluations of the
      productive sound system and the metalinguistic ability to classify phonological
      information, with particular emphasis on fricatives. Then, children were enrolled
      in clinical treatment aimed at accurate production of fricatives. Following
      treatment, production and classification abilities were again tested. Results
      indicated that if a child's productive knowledge of distinctive featural
      contrasts changed following treatment, there was also a corresponding change in
      conceptual knowledge. The specific featural dimensions that were used to classify
      phonological information were either in parallel to, or in advance of, those
      features also used in production by the child. Conceptual knowledge was thus
      equal to or better than productive knowledge for these children.

PMID- 9770911
TI  - Children's comprehension of unfamiliar regional accents: a preliminary
      investigation.
AB  - The effect of regional accent on children's processing of speech is a
      theoretically and practically important aspect of phonological development that
      has been little researched. 48 children from London, aged four and seven years
      old, were tested on their ability to repeat and define single words presented in
      their own accent and in a Glaswegian accent. Results showed that word
      comprehension was significantly reduced in the Glaswegian condition and that four
      year-olds performed less successfully than seven-year-olds. Both groups made
      similar numbers of lexical misidentifications, but the younger children were more
      likely to fail to access any word at all. On the repetition task, the younger
      children showed a different pattern of errors to the older children, their
      productions being apparently more influenced by the phonetics of the Glaswegian
      stimuli. It is suggested that such phonetic responses are related to the younger
      children's failure to map the unfamiliar accent onto their own phonological
      representations. It is proposed that the lexical misidentifications, common to
      both age groups, are more likely to be induced by lack of context. The paper
      concludes with discussion of implications of these findings for our understanding
      of how children develop the ability to process unfamiliar regional accents.

PMID- 9770912
TI  - Sources of child vocabulary competence: a multivariate model.
AB  - This study examines sources of individual variation in child vocabulary
      competence in the context of a multivariate developmental ecological model.
      Maternal sociodemographic characteristics, personological characteristics, and
      vocabulary, as well as child gender, social competence, and vocabulary competence
      were evaluated simultaneously in 126 children aged 1;8 and their mothers.
      Measures of child vocabulary competence included two measures each of spontaneous
      speech, experimenter assessments, and maternal reports. Maternal measures, from
      proximal to distal, included vocabulary, verbal intelligence, personality,
      attitudes toward parenting, knowledge of parenting, and SES. Structural equation
      modelling supported several direct unique predictive relations: child gender
      (girls higher) and social competence as well as maternal attitudes toward
      parenting predicted child vocabulary competence, and mothers' vocabulary
      predicted child vocabulary comprehension and two measures of mother-reported
      child vocabulary expression. In addition, children's vocabulary competence was
      influenced indirectly by mothers' vocabulary, social personality, and knowledge
      of child development. Maternal vocabulary itself was positively influenced by
      SES, maternal verbal intelligence, and mothers' knowledge about parenting.
      Individual variation in child vocabulary competence might best be understood as
      arising within a nexus of contextual factors both proximal and distal to the
      child.

PMID- 9770913
TI  - A developmental study of the acquisition of Russian colour terms.
AB  - We report a study of the acquisition of colour terms by Russian children which
      had two main aims: first, to test Berlin & Kay's (1969) theory of colour
      universals using acquisition order as a measure of basicness; and secondly, to
      see if the two BLUE terms of Russian are genuinely basic. Two hundred children
      aged from three to six-years-old were tested on three colour-tasks--colour term
      listing, colour term production and colour term comprehension. To a reasonable
      approximation, the order of colour term acquisition was in accord with Berlin &
      Kay's theory, but the data are also consistent with the weaker claim that primary
      terms tend to be learned before derived terms. On balance the data were
      consistent with Russian exceptionally, having an extra term for the BLUE region.
      But, the two BLUE terms--goluboj 'light blue' and sinij 'dark blue'--were
      confused more often than other pairs of terms even by the five- to six-year-old
      sample.

PMID- 9770914
TI  - Object naming at multiple hierarchical levels: a comparison of preschoolers with
      and without word-finding deficits.
AB  - According to the storage hypothesis (Kail & Leonard, 1986), word-finding deficits
      in young children are not the direct results of deficient retrieval strategies;
      they are a manifestation of a general delay in language development that affects
      lexical storage. In the current study, we explored one aspect of lexical storage,
      the hierarchical organization of the semantic system, in 13 preschoolers with
      word-finding deficits (WF) and 13 preschoolers with normal language abilities
      (ND), ranging in age from 3;3 to 6;7. The children named a series of objects at
      multiple levels of the noun hierarchy in response to contrast questions (e.g. for
      rose they were asked, 'Is this an animal?' to elicit plant [superordinate]; 'Is
      this a tree?' to elicit flower [basic]; 'Is this a dandelion?' to elicit rose
      [subordinate]). Both groups readily named at multiple levels, providing evidence
      of hierarchical organization of the lexicon. However, there were several
      differences between WF and ND groups that suggested that WF children did not have
      enough stored information to discriminate between similar semantic neighbours. We
      conclude (1) that hierarchical organization of the semantic lexicon is a robust
      developmental phenomenon, apparent in both ND and WF preschoolers and (2) that
      the word-finding deficits of preschoolers appear to reflect insufficient depth
      and breadth of storage elaboration rather than deficits in hierarchical semantic
      organization.

PMID- 9770915
TI  - Home care: images and reflections.

PMID- 9770916
TI  - Death at home: challenges for families and directions for the future.

PMID- 9770917
TI  - An assessment of open communication between people with terminal cancer, caring
      relatives, and others during home care.

PMID- 9770918
TI  - Congruence between patients' and family caregivers' perceptions of symptom
      distress in patients with terminal cancer.

PMID- 9770919
TI  - Home care for children with life-threatening illness.

PMID- 9770920
TI  - Nursing interventions for newly diagnosed older cancer patients facing terminal
      illness.

PMID- 9770922
TI  - Psychosocial needs of patients and families.

PMID- 9770921
TI  - The feasibility and advisability of administering home blood transfusions to the
      terminally ill patient.

PMID- 9770923
TI  - The interaction between family physicians and palliative care consultants in the
      delivery of palliative care: clinical and educational issues.

PMID- 9770924
TI  - Integration of pain education in home care.

PMID- 9770925
TI  - Palliative care education for community-based family physicians: the development
      of a program, the evaluation, and its consequences.

PMID- 9770926
TI  - Community education in palliative medicine.

PMID- 9770927
TI  - Educating doctors in palliative medicine: development of a competency-based
      training program.

PMID- 9770928
TI  - Closure of an in-hospital palliative home care service.

PMID- 9770929
TI  - Eighteen years of home care: from assistance by phone to a complete service
      within the health care system.

PMID- 9770930
TI  - The Dorothy Ley Hospice Day Respite Program.

PMID- 9770931
TI  - Pall-Connect: a support network for community physicians.

PMID- 9770932
TI  - Assessment and management of patients who refuse life-prolonging treatments.

PMID- 9770933
TI  - Development and validation of a questionnaire designed to measure foot-health
      status.
AB  - The aim of this study was to apply the principles of content, criterion, and
      construct validation to a new questionnaire specifically designed to measure foot
      health status. One hundred eleven subjects completed two different questionnaires
      designed to measure foot health (the new Foot Health Status Questionnaire and the
      previously validated Foot Function Index) and underwent a clinical examination in
      order to provide data for a second-order confirmatory factor analysis. Presented
      herein is a psychometrically evaluated questionnaire that contains 13 items
      covering foot pain, foot function, footwear, and general foot health. The tool
      demonstrates a high degree of content, criterion, and construct validity and test
      retest reliability.

PMID- 9770934
TI  - The demography of limb dominance, body-mass index, and metatarsus adductus
      deformity.
AB  - To test the null hypothesis that limb dominance (laterality) and side of
      complaint are not associated in a diverse population, nearly 400 patients (40%
      male, 60% female) of varying age and body size from three South Florida podiatric
      medical teaching facilities were surveyed in 1995-1996. Radiographs of feet were
      available for 15% of the patients, and the metatarsus adductus angle was measured
      on each x-ray. The typical patient was a women (median age, 49 years) of average
      body weight and average body-mass index. No statistical association was found
      between laterality and side of complaint in the broader sample, although a
      significant association did appear in the subsample of patients with bilateral x
      rays. The prevalence of metatarsus adductus deformity (metatarsus adductus angle
      > 15 degrees) among patients with x-rays was 62%. No sex-specific, age-specific,
      or body size-specific associations were found between handedness and metatarsus
      adductus deformity.

PMID- 9770935
TI  - Geometric models that classify structural variations of the foot.
AB  - The author presents a description of three geometric models to serve as a
      framework for establishing a numerical classification system of unlimited
      refinement for structural variations of the foot and foot types. Such a
      classification system may identify different forms (foot types) that may be
      closely aligned to complex movements of the foot (dynamic foot function). This
      may help in the diagnosis and treatment of biomechanical disabilities. Clinical
      evaluations are based on radiographic landmark data from weightbearing
      radiographs.

PMID- 9770936
TI  - Characterization of plantar verrucae among individuals with human
      immunodeficiency virus.
AB  - Plantar verrucae, caused by human papillomavirus (HPV), are commonly found in
      patients who have tested positive for the antibodies to human immunodeficiency
      virus (HIV). A better understanding of the characteristics of plantar verrucae in
      HIV+ patients in needed. A pilot study was conducted concentrating on three
      characteristics--the size, the number, and the clinical type--of verrucae present
      in this population. These parameters were studied in HIV+ and HIV- populations,
      and they were evaluated in relation to the CD4 levels of HIV+ individuals. The
      HIV+ individuals presented with plantar verrucae that were larger and more
      numerous than those found in HIV- individuals. The HIV+ population presented with
      all three clinical types of plantar verrucae and had significantly more mosaic
      type warts than did HIV- individuals. The three characteristics did not correlate
      with CD4 cell counts, suggesting that the severity and extent of HPV infection do
      not depend on the level of immunosuppression of the HIV+ patient.

PMID- 9770937
TI  - Perimortem calcaneal and talar fractures sustained in a military air crash in
      Vietnam.
AB  - The authors report on the skeletal elements of a minimum of 37 men who died in
      1965 when their C-123 cargo airplane crashed into a mountainside in South
      Vietnam. Natural environmental processes reduced their bodies to skeletons; these
      osseous remains were recovered from the crash site nearly 10 years later. Among
      the remains were the calcanei and tali of at least 37 people. These bones, devoid
      of soft tissue, provide a rare opportunity to examine and document the pattern of
      perimortem fractures in multiple individuals who died in the same incident. This
      case also provides information on a range of variability of skeletal fractures
      that is unavailable in comparative skeletal collections, and that might be
      overlooked with radiography or during physical examination.

PMID- 9770938
TI  - Improved healing with a collagen-alginate dressing in the chemical matricectomy.
AB  - A prospective clinical trial was conducted to evaluate the efficacy of a collagen
      alginate wound dressing in the postoperative management of chemical
      matricectomies. The study involved 20 patients and 23 separate procedures. The
      collagen-alginate-dressing treatment group had an average healing time of 24.4
      days, compared with 35.8 days for the control group, which received treatment
      consisting of soaks and daily dressing changes (P < .05). The authors suggest
      that using a collagen-alginate wound dressing in the postoperative management of
      chemical matricectomies will shorten healing time, thus reducing infection rates
      and increasing patient compliance and satisfaction.

PMID- 9770939
TI  - Clear cell sarcoma in the first metatarsal. An unusual case.
AB  - Clear cell sarcoma is an uncommon malignant neoplasm that, on rare occasion,
      invades osseous structures. The authors present a case of clear cell sarcoma that
      appears to have an osseous origin and that was discovered on a routine radiograph
      of the foot.

PMID- 9770940
TI  - Podiatric medical resources on the Internet. A second update.

PMID- 9770941
TI  - ECG of the month. U turns. Inverted U waves.

PMID- 9770942
TI  - Vocal cord paralysis.
AB  - Vocal cord paralysis is a multifacted problem that affects patients of all ages
      and presents initially to a wide range of healthcare professionals. It can cause
      laryngeal dysfunction ranging from slight hoarseness to life-threatening airway
      obstruction. When confronted with a patient with new onset vocal cord paralysis,
      the physician should determine the etiology of the paralysis. Only after an
      accurate diagnosis, can restoration of laryngeal function be addressed.
      Peripheral lesions injuring the vagus nerve or its branches are responsible for
      90% of all vocal cord paralysis. Etiologies include neoplasms, surgical
      iatrogenic injury, and blunt and penetrating trauma in the head, neck, and
      thorax. Thyroid surgery has historically been accountable for almost a third of
      reported unilateral vocal cord paralyses. However, recent review has demonstrated
      a dramatic reduction in this incidence to less than 5%. Numerous treatment
      options exist for patients with vocal cord paralysis. These treatments can
      drastically reduce the social and economic disability incurred by these patients.

PMID- 9770943
TI  - Radiology case of the month. Painless microhematuria. Bladder tumor.

PMID- 9770944
TI  - The journal 150 & 100 years ago. August 1848 and 1898.

PMID- 9770945
TI  - A 65-year-old woman with heart failure.
AB  - The differential diagnosis for a 65-year-old woman with heart failure is
      discussed in the setting of a clinicopathological conference at Louisiana State
      University Medical Center in Shreveport. The discussion includes precipitating
      factors, pathophysiology, and etiologies of heart failure.

PMID- 9770946
TI  - Genetics, aging, and the heart.
AB  - Heart disease remains the most frequent cause of death in the general population
      and is intimately related to aging. Either extreme premature aging or marked
      longevity may be monogenic, but in most humans aging is a complex polygenic
      phenomenon. Hypercholesterolemia and hypertension are important factors. Cardiac
      amyloidosis and vascular elastin degradation may be separate factors. Humans with
      the greatest longevity are relatively refractory to atherosclerosis. Frequencies
      of heart deaths among relatives of a heart-death proband without
      dyslipoproteinemia conform to expectations of a polygenic trait. Careful,
      attentive medical management of major environmental factors and of heart
      senescence can result in more successful aging.

PMID- 9770947
TI  - Breast leiomyoma.
AB  - Smooth muscle neoplasms exist as a spectrum of pathologic processes ranging from
      benign leiomyoma to anaplastic leiomyosarcoma. Although these tumors typically
      occur in regions where there is an abundance of smooth muscle, they may also be
      derived from the muscularis of the gastrointestinal tract or the media of blood
      vessels. The majority of breast leiomyomas are contiguous with the muscular
      components of the nipple areolar complex. Strong, in 1913, is credited with the
      early descriptions of leiomyoma of the mammary gland. There have been relatively
      few reports of this entity since Strong's initial description. Smooth muscle
      neoplasms of the breast present unique clinical challenges for which therapeutic
      decisions are based on criteria extrapolated from the management of similar
      tumors at other sites. This report high-lights key clinical and pathologic
      findings in a postmenopausal woman with a discrete breast mass of benign smooth
      muscle histology.

PMID- 9770948
TI  - Report from the front lines: rural Medicaid primary care providers as gatekeepers
      of rural health service networks.
AB  - This study of primary care practitioners in Louisiana's Medicaid managed care
      program, Community Care, focused on the program's implementation and perceived
      impact. PCPs were interviewed to assess their perceived responsibilities as
      gatekeepers and how well they believed the system facilitated or impeded their
      fulfillment of those responsibilities, to examine issues of access and quality,
      and to determine their knowledge and use of local referral networks. Findings
      indicate that although they appreciated the financial stability derived from
      having a larger patient base and understood their roles well, they were concerned
      with several facets of the program, including perceived limitations imposed on
      their medical decision making, an added burden of paperwork, and a lack of both
      downward and upward communication. They also believed the referral network of
      available providers for medical and social services to be more limited for their
      Medicaid patients than for their private patients. Policy implications are
      discussed.

PMID- 9770949
TI  - Creating great leaders in health care, with a vision for the new millennium.

PMID- 9770950
TI  - The eradication of tobacco: a moral imperative.

PMID- 9770951
TI  - Physician contracts with practice management companies.

PMID- 9770952
TI  - Cardiovascular risk factors in economically disadvantaged women: a study of
      prevalence and awareness.
AB  - This study examined the prevalence of cardiovascular risk factors among low
      income women and assessed the level of awareness and attitudes about these risk
      factors in the community. A survey instrument was developed and administered by a
      single researcher to a convenience sample of women in health clinics and
      nonclinical community settings. These settings included: an academic clinic,
      community clinics, women's shelters, free meal sites, community centers, public
      housing units, and private homes in Philadelphia, Pennsylvania. Two hundred two
      women were selected without regard to age or race. The mean number of
      cardiovascular risk factors per subject was 2.6 (SD 1.4). Each of eight
      established cardiovascular risk factors was identified by 4% to 34% of subjects.
      Among those women with a specific risk factor, only 0% to 45% reported that they
      were at increased risk due to the presence of that factor. The prevalence of
      cardiovascular risk factors among low-income women is substantial. Knowledge and
      understanding of these risk factors is suboptimal, particularly among women
      personally affected by risk factors for cardiovascular disease.

PMID- 9770954
TI  - Partner notification and focused intervention as a means of identifying HIV
      positive patients.
AB  - Partner notification as a means of contact tracing human immunodeficiency virus
      (HIV)-infected persons remains controversial. It is argued against by many gay
      activists, while primary public health officials and leaders in ethnic
      communities continue to support this as a means of identifying unknown cases.
      Human immunodeficiency virus-positive patients were interviewed to determine if
      partner notification could be a useful instrument. Based on interviews, patients
      at risk of infection through heterosexual contact were able to identify most of
      their sexual partners; the majority of these patients were women. Twenty-two of
      22 women infected heterosexually were able to identify all of their sexual
      partners. Five of 8 heterosexual men were able to identify all of their sexual
      partners, but these men were infected through intravenous drug use. Six of 44
      homosexual men interviewed were able to make these identifications. Two focus
      groups of homosexual men who were HIV-positive patients were organized; each was
      asked one question. Men in group B were asked if they could identify HIV-positive
      persons whom they suspected were not in a treatment program. Men in group A were
      asked if they they thought they knew HIV-positive persons still practicing unsafe
      sex. Thirteen of the 14 patients in group A were able to identify 30 persons they
      felt were still practicing unsafe sex; 17 of 30 tested HIV-positive and 9 were
      unaware of their status. The 14 patients in group B identified 15 persons they
      felt were HIV-positive; 11 were found to be HIV-positive and 8 were unaware of
      their status. These findings suggest that partner notification definitely has a
      role in heterosexual contact tracing, and focused intervention is a more cost
      effective approach to early intervention.

PMID- 9770953
TI  - Multidrug-resistant enterococci: the dawn of a new era in resistant pathogens.
AB  - Resistant enterococci, especially vancomycin-resistant enterococci, have rapidly
      become an important nosocomial pathogen. They are increasingly prevalent among
      hospitalized patients, patients with serious chronic illnesses, and
      immunosuppressed patients. Risk factors identified include previous antibiotics,
      exposure to contaminated equipment, and close proximity to infected patients.
      Treatment of multidrug-resistant pathogens has become increasingly difficult,
      with increased morbidity and mortality in these patients. Strict infection
      control measures remain the mainstay in the management of these infections.

PMID- 9770956
TI  - Early diagnosis of conjoined twins using two-dimensional color Doppler and three
      dimensional ultrasound.
AB  - Transvaginal three-dimensional (3-D) and color Doppler ultrasound were used to
      establish a first-trimester definitive diagnosis and classification of
      thoracoomphalopagus conjoined twins following two-dimensional (2-D)
      transabdominal and transvaginal scans that indicated twin gestation of uncertain
      classification. Color Doppler in combination with 3-D ultrasound can be a useful
      complement to 2-D ultrasound to confirm early diagnosis and determine the extent
      of organ sharing and definitive classification of conjoined twins.

PMID- 9770955
TI  - Pattern of breast cancer among white-American, African-American, and nonimmigrant
      west-African women.
AB  - This study reviews the current understanding of the pattern of breast cancer
      among whites, African Americans, and West Africans who have never immigrated to
      the US to find better ways of improving the prevention, early detection, and care
      of breast cancer world-wide. In the United States, the behavior pattern of breast
      cancer in African-American women differs from that of white women. Among the
      three populations, breast cancer appears to be least common in nonimmigrant West
      African women. The peak incidence in African Americans and West Africans occurs
      around the premenopausal period while it occurs postmenopausal period in whites.
      Also, unlike white women, West-African and African-American women present late
      for treatment with a greater cancer burden and consequently lower survival rates.
      The predominant histological type is infiltrating ductal carcinoma in the three
      groups but the highest percentage (33%) of infiltrating poorly differentiated
      anaplastic carcinoma occurs in West Africans. Menstrual and obstetric history,
      obesity, and high body mass index status appear to be greater specific risk
      factors among African Americans than among West Africans. African Americans and
      West Africans have three "Ls" in common: late stage in seeking treatment, lower
      age at peak incidence with severe tumor burden, and consequently lower survival
      rates. There is a need for more detailed population-based research at molecular
      levels to elucidate the basis for some of these features.

PMID- 9770957
TI  - [Current views about etiology and pathogenesis of systemic vasculitis: role of
      autoantibodies and disturbances of cellular immunity (part II)].

PMID- 9770958
TI  - [Pathogenesis, diagnosis and therapeutic policy in viral myocarditis and dilated
      cardiomyopathy].

PMID- 9770959
TI  - [Vitamins and trace elements in abnormal hemostasis].

PMID- 9770960
TI  - [Diagnosis of primary fibromyalgia: clinical criteria].

PMID- 9770961
TI  - [Stress echocardiography in localization of coronary atherosclerosis and
      assessment of it severity].
AB  - 193 patients with coronary heart disease were examined to study potentialities of
      noninvasive diagnosis of coronary artery lesions, their location and severity
      using transesophageal echocardiography in combination with transesophageal
      stimulation. This method of stress-test proved highly sensitive (89%) and
      specific (84%) in noninvasive diagnosis of both location of coronary
      atherosclerosis and its severity (stenosis, subtotal stenosis, occlusion) and
      extension.

PMID- 9770962
TI  - [Pulse therapy with prospidin and methotrexate: comparative efficacy in
      rheumatoid arthritis (12-month controlled study)].
AB  - Efficiency of pulse-therapy with prospidin (500 mg for 5 days in hospital, 500
      1000 mg for a month as maintenance) and methotrexate (30 mg a week i.v. in
      hospital, 7-10 mg a week as maintenance) was investigated in 93 patients with
      severe RA. The response to prospidin and methotrexate arose quickly (within 10-14
      and 4-5 weeks, respectively) and occurred in 73 and 70% of patients,
      respectively. Withdrawal of the drug was caused by side effects of methotrexate
      (19.3%) and resistance to prospidin (23.2%).

PMID- 9770963
TI  - [Specific approach to prevention and treatment of acute pneumonia in alcoholics].
AB  - Updated diagnostic and therapeutic approaches to acute pneumonia in chronic
      alcoholics suffering from alcoholic delirium resulted in lowering of acute
      pneumonia lethality in specialized medical clinics for alcoholics and drug
      addicts.

PMID- 9770964
TI  - [Electrogastrography in diagnosis of ulcerative pyloroduodenal stenosis].
AB  - Skin electrogastrogram was made in 40 healthy controls and 32 patients with
      ulcerative pyloroduodenal stenosis in fasting condition and after mixed meal.
      Fasting frequency of gastric bioelectric activity (BA) was similar in the
      patients and the controls (2.65 +/- 0.008; 2.65 +/- 0.008; p < 0.01). BA
      frequency unstability factor (FUF) was not so high in patients compared to
      controls (13.9 +/- 0.07; 15.3 +/- 0.11; p < 0.01). The meal produced a
      significant rise in the frequency, amplitude and a decrease in FUF of gastric BA
      in the patients and controls but in patients a fall in FUF was greater. A rise in
      the amplitude of gastric BA in patients was more pronounced than in controls
      (250.6 +/- 5.17%, 162.0 +/- 2.23%; p < 0.01). In patients the amplitude increased
      greater in compensated stenosis, weaker--in decompensated stenosis. The changes
      in gastric BA amplitude varied with severity of pyloroduodenal stenosis.

PMID- 9770965
TI  - [Therapeutic response to alpha-interferon in chronic alcoholics with viral
      hepatitis C].
AB  - Hepatitis C was treated with interferon alpha in chronic alcoholics and control
      subjects without alcoholism. The results show that ethanol is an independent risk
      factor in natural progression of chronic hepatitis C. Moreover, it dose
      dependently reduces probability of getting a reliable response to interferon
      therapy. This makes using interferon alpha treatment of hepatitis C in chronic
      alcoholics doubtful.

PMID- 9770966
TI  - [Clinicofunctional changes of heart in patients with clinically different
      variants of toxic diphtheria].
AB  - A clinicofunctional examination of 72 patients with toxic diphtheria (mean age
      36.8 +/- 7.1 years) has been made to study the course and outcome of diphtheria
      related damage to the heart. It is shown that clinical symptoms of myocarditis
      became more prominent with growing severity of diphtheric infection and evidenced
      for diffuse affection of the left ventricle. EchoCG detected defective systolic
      function which in patients with unfavorable prognosis was associated with
      thickening of the myocardium and dilatation of the left ventricular chamber. 24-h
      Holter monitoring registered shifts in the end part of the ECG ventricular
      complex and various abnomalities in the heart rhythm. Focal myocardial lesions
      manifested with supraventricular and solitary ventricular extrasystoles. In
      diffuse myocarditis frequent ventricular extrasystoles prevailed. At autopsy,
      structural myocardial changes in toxic diphtheria were confirmed.

PMID- 9770967
TI  - [Antisecretory effects of quamatel and gastrocepin in duodenal ulcer: comparison
      with intragastric pH-metry].
AB  - Antisecretory effect of intravenous quamatel (Q) and gastrocepin (G) was studied
      in 59 patients with duodenal ulcer. Mean maximal pH and delta-pH in antral
      portion of the stomach and its body were similar for Q and G, but pH responded to
      Q administration faster. The antisecretory effect of Q was more pronounced in
      males and young patients and was inversely proportional to initial acidity.

PMID- 9770968
TI  - [Optimization of hypotensive therapy in hypertensive patients with new beta-1
      selective long-acting adrenoblocker].
AB  - 20 hypertensive subjects entered the trial of kerlon (Searle, USA). Central
      hemodynamics was studied by tetrapolar chest rheography according to J. Franz.
      Therapeutic response to beta-1-adrenoblocker kerlon in hypertension was assessed
      by hemodynamic indices and acute pharmacological test. The effect was found to
      depend on the initial hemocirculation type. In hyperkinetic hemodynamics lowering
      of blood pressure was due to diminution of the cardiac index, in eukinetic and
      hypokinetic types- to a decrease in the total peripheral vascular resistance.

PMID- 9770970
TI  - [Bioethics of medical practitioner].

PMID- 9770971
TI  - [Proteinuria].

PMID- 9770972
TI  - [Insomnia].

PMID- 9770973
TI  - [Clinical variants of infectious endocarditis in toxicomania].

PMID- 9770974
TI  - [Homeopathy: principles, place and opportunities in current therapy].

PMID- 9770975
TI  - [Austrian reform of university medical education in the second half of XVIII
      century. Communication 2. Development of curricula for training doctors by I.P.
      Frank].

PMID- 9770976
TI  - [G.A. Zakhar'in: at the critical turning point of clinical medicine (part II].

PMID- 9770977
TI  - [Clinical usefulness of immunocytochemical and genetic-molecular investigations
      in diagnosis of neoplasms of organs of sight].
AB  - AIM: To determine the usefulness of immunocytochemical (icch) and genetic
      molecular (g-m) investigations in diagnosing neoplasm cases of eye, eye socket
      and eyeball, and to determine how far these investigations precise the diagnosis
      made using other methods. MATERIALS AND METHODOLOGY: 38 patients with neoplasm
      cases of eye, eye socket and eyeball were examined, performing routine
      ophthalmological examinations and auxiliary examinations such as USG, TK,
      roentgenography. Material for the cytological examination, icch and g-m, was
      obtained by way of fine needle biopsy (bac) in 18 patients with tumor of eye
      socket, conjunctiva or eyelid and in 1 patient with intraocular tumour. In the
      remaining patients with intraocular tumours print smears after eyeball removal
      were made. RESULTS: 100% conformability of cytological diagnoses, supplemented
      with icch evaluation, with the final diagnosis was found. The g-m examination
      made in 2 cases of lymphoma confirmed the clonal nature of the hyperplasia.
      CONCLUSIONS: Icch examinations make possible the diagnosis in cytological smear
      of histological type of mature and low-differentiated neoplasms. In tumours of
      eye and eye socket cases the diagnosis thus made allows to take a decision on
      conservative or operative therapy. In intraocular examinations these examinations
      find applications in diagnostically especially difficult cases.

PMID- 9770978
TI  - [The use of perfluorocarbon liquid in the surgical removal of lenses luxated to
      the vitreous cavity].
AB  - BACKGROUND: Removal of lenses dislocated to the vitreous cavity can be hazardous.
      The use of perfluorocarbon liquids during pars plana vitrectomy may reduce the
      risk of intraoperative and postoperative complications. We report our experience
      in using this surgical technique. MATERIAL AND METHODS: The authors describe a
      series of 14 patients in whom a posteriorly dislocated crystalline (11 eyes) or
      intraocular (3 eyes) lens was successfully removed with the use of
      perfluorodecalin through the limbal incision. Simultaneously, posterior chamber,
      scleral fixation IOLs were implanted in 10 cases and anterior chamber IOL in one
      case. In one patient AC IOL was implanted secondarily. RESULTS: With a minimum
      follow-up of one month (average, 8 months), the visual acuity improved in 4 eyes,
      remained the same in 10, and worsened in one eye. Very good visual acuity (5/5
      5/10) was achieved in 86% of patients. Complications were not frequent and not
      severe despite one case of retinal detachment. CONCLUSIONS: Application of pars
      plana vitrectomy and the use of liquid perfluorocarbon allow for the safe
      management of eyes with luxated lenses.

PMID- 9770979
TI  - [Survival rate of young patients with malignant choroidal melanoma after
      conservative treatment].
AB  - PURPOSE: The purpose of this study was estimation of the results of treatment and
      probability of survival in patients with malignant choroidal melanoma at the age
      under 40 at the time of diagnosis. MATERIAL AND METHODS: 110 patients were
      treated, including 61 women and 49 men. The follow-up time was 5-25 years, in the
      diagnosis several different methods were used: ophthalmoscopy, ultrasonography,
      transillumination, and in some cases additionally computer tomography, magnetic
      resonance imaging, and fluorescein angiography. All patients were also
      periodically tested for metastases. The following methods of treatment of
      melanoma were applied: xenon-arc photocoagulation (21 eyes), brachytherapy (33
      eyes), combined treatment (45 eyes). In 58 patients enucleation, and in 2
      exenteration were necessary. RESULTS AND CONCLUSIONS: Positive results of
      treatment were obtained in 48 patients (43.7%), 24 patients died because of
      metastases. The chance of survival was smaller in women, in cases of greatest
      dimension of the tumours, when the tumours were located in peripheral areas of
      the eye fundus, when the tumours infiltrated the optic nerve, and in epithelioid
      cell type of tumour.

PMID- 9770980
TI  - [The surgical treatment of strabismus and diplopia in Graves-Basedow
      ophthalmopathy].
AB  - PURPOSE: The aim of the study is to evaluate results of surgical treatment of
      strabismus and diplopia in Graves-Basedow ophthalmopathy. MATERIAL AND METHODS:
      The surgical procedure was performed in 40 patients with horizontal strabismus,
      horizontal strabismus with vertical deviation or isolated vertical strabismus.
      There were performed 86 surgical procedures on the eye muscles (in 20 cases
      adjustable sutures were used). RESULTS: Recovery or recovery without binocular
      single vision was observed in 27 cases (67.5%) and improvement in 11 cases
      (27.5%). CONCLUSIONS: The necessary conditions of surgical treatment are stabile
      euthyreoid state, the stabilization of the angle of strabismus and diplopia. The
      best results of operation are in the prefibrosis period of the muscle directly.
      The surgical procedures of weakening the function of muscles and adjustable
      sutures are recommended. The operations of several stages and atraumatic should
      be performed.

PMID- 9770981
TI  - [Visual evoked potentials and static perimetry in functional visual deficits].
AB  - The author presents application of visual evoked potentials and static perimetry
      in hysterical amblyopia, psychical blindness, malingerers, amblyopia, cortical
      blindness and visual acuity assessment in infants. The author emphasizes the
      influence of multiple factors on the results and interpretation of the
      examination.

PMID- 9770982
TI  - [Results of investigations of visual evoked potentials in the treatment of
      amblyopia].
AB  - PURPOSE: The aim of the study is to demonstrate the changes in visual evoked
      potentials (VEP) in treatment of amblyopia. MATERIAL AND METHODS: Pattern
      reversal VEP of 28 children treated because of amblyopia and 16 healthy persons
      were analysed. Before treatment and after treatment the results of the
      interocular amplitude difference ratio and interocular latency difference ratio
      were compared with standards. RESULTS: After treatment of amblyopia the
      percentage of normal interocular amplitude and latency difference ratios
      increased. CONCLUSION: Study of pattern VEP enables monitoring of amblyopia
      treatment.

PMID- 9770983
TI  - [Changes observed in electrophysiological investigations in amblyopia and
      strabismus].
AB  - PURPOSE: The aim of the investigations was to state whether strabismic amblyopia
      and aniseiconia can be connected with disturbance of visual evoked potentials
      (VEP). MATERIAL AND METHODS: VEP investigations in 28 children with amblyopia,
      aged from 4 to 12 years and in 16 healthy persons were performed. Analysis of
      amplitude and latency of the positive wave P1 and negative wave N2 in the healthy
      eye and in the amblyopic eye was done. RESULTS: Statistical significance of the
      decrease of average amplitude of the fold in the record of the amblyopic eye at
      stimulation with small patterns was found. CONCLUSION: In amblyopia the amplitude
      of the pattern reversal VEP is decreased. Changes in the record of VEP in
      amblyopic eyes testify to the presence of transmission lesion in the retrobulbar
      visual pathway.

PMID- 9770984
TI  - [Solar retinopathy].
AB  - The purpose of this study is the present clinical evaluation of 21 patients
      (number of affected eyes--33), who watched eclipse of the sun on 12 October 1996.
      All patients had general ophthalmic examination with emphasis on visual acuity,
      visual field, Amsler test, fluorescein angiography and fundus appearance. Eleven
      out of 21 patients had at least one follow up examination (number of affected
      eyes--17). None of the patient received any treatment. All patients revealed
      tiny, central scotomata--positive Amsler test and decreased visual acuity on the
      first visit; reading Snellen chart could be improved in all patients by adequate
      head tilt or eye movement (improvement up to 3 Snellen chart lines). No signs of
      retinopathy were observed in two eyes with uncorrected refractive error and one
      amblyopic eye. After 7-8 weeks the visual acuity was decreased to 5/30 in two
      eyes and to 5/10 in ten eyes. In all those eyes persisted a tiny, central
      scotoma. Looking at the eclipse of the sun in spite of using primitive eye
      protection may cause irreversible retinal damage. Return of visual acuity to 5/5
      does not always imply complete recovery because of persistent central scotoma.

PMID- 9770985
TI  - [The different aspects of ophthalmological disability on the own experience].
AB  - PURPOSE: The purpose of the study was to present the most often reasons of
      ophthalmological invalidity. MATERIAL: The analysis was based on 154 court's
      opinions. RESULTS: Monopia, high myopia and different congenital diseases were
      the most frequent reasons of ophthalmological invalidity.

PMID- 9770986
TI  - [Results of radial keratotomy and photorefractive keratectomy in patients'
      assessment].
AB  - PURPOSE: The aim of the study is the presentation of RK and PRK results in
      patients' assessment. MATERIAL AND METHODS: Questionnaire forms were sent to 100
      patients after RK and 120 after PRK between 12 and 24 months after surgery.
      Preoperative refractive error in both groups was similar: -6.76 D sph in RK group
      and(--)-6.25 D sph in PRK group. Questionnaire forms consisted of 12 questions
      about the decision of operation, its course, possible complications and results.
      RESULTS: 76 (76%) patients after RK and 94 (78.25%) after PRK answered the
      questionnaires. 96% of patients after RK and 98.9% after PRK were satisfied with
      achieved results. 56.4% of PRK and 29% of RK patients answered that healing was
      painful and very painful. 57% of patients after RK and 49% after PRK complained
      of complications after surgery (fluctuations of vision, glares). Majority of
      patients in both groups would accept the procedure again. CONCLUSIONS: Both RK
      and PRK were positively assessed by the patients, however slightly higher level
      of satisfaction was in PRK group. There were also fewer complications in this
      group.

PMID- 9770987
TI  - [Reciprocal action].

PMID- 9770988
TI  - [Neurosteroids].

PMID- 9770989
TI  - [Breast cancer: importance of environmental factors in its formation].

PMID- 9770990
TI  - [Cannabinoids as analgesics?].

PMID- 9770991
TI  - [Total parenteral nutrition. History. Present time. Future].
AB  - Total parenteral nutrition (TPN) has been available for only 30 years. However,
      history in this field goes back more than 350 years with the first landmark being
      the description of general blood circulation by William Harvey in 1628. His
      discovery is the anatomical basis for intravenous infusions. Many investigations
      were performed during the following centuries showing that solutions containing
      electrolytes and glucose could be given intravenously in man. The accumulated
      knowledge of protein metabolism formed the basis for studies on intravenous
      nutrition with protein hydrolysates, peptides and amino acids. The observation in
      the late 30-s by Robert Elman that amino acids in the form of protein hydrolysate
      could be safely administered intravenously in man was the first major step toward
      TPN. During the following years, major efforts were made to find methods to
      prepare infusion solutions with a high energy content and low osmotic pressure.
      The most realistic alternative seemed to be fat in the form of an emulsion. Many
      studies of a large number of various fat emulsions were made however, all of
      these emulsions caused severe adverse reactions in man. The first safe fat
      emulsion, intralipid, was made available in the early 60s. This was the second
      major step toward TPN. It was then no problem to include vitamins, electrolytes
      and trace elements in the fat emulsions and the solutions of amino acids and
      glucose. A few years later it was shown that a central venous catheter could be
      used to administer the infusion fluid intravenously. Many clinical investigations
      and reports have shown that the newly developed intravenous nutritional regimens
      are adequate alternatives to the ordinary diet. In this way it has been possible
      to maintain or obtain a good nutritional condition in most situations when oral
      or tube feeding can not be used. TPN has been shown to be of very great clinical
      importance to prevent and treat starvation often related to high morbidity and
      mortality.

PMID- 9770992
TI  - [Parenteral nutrition in postoperative period].
AB  - Results of surgical procedures in malnutrished patients are worse than in well
      nutrished patients. Perioperative nutritional treatment lead to diminished
      percentage of postoperative complications and mortality. Authors presents the
      influence of early postoperative enteral nutrition in 35 malnutrished patients on
      body composition and anthropometrical and biochemical parameters of their
      nutritional status. Results shows that enteral nutrition in postoperative phase
      can decrease catabolic effect of surgical treatment.

PMID- 9770993
TI  - [Gastroscopic criteria and most frequent pain in bile reflux gastritis].
AB  - The aim of the paper was consolidation a gastroscopic cryterious and oftenest
      sufferings in case bile reflux gastritis. In this purpose carry over analysis
      1000 successive gastroscopic study performed in case discomfort in abdominal. In
      38.2% confirmed on basis gastroscopic exploration presence of bile in the
      stomach. In 19.1% recognised presence of bile as results bile reflux because of
      insufficiency duodeno-pyloric instalation. In 6.2% confirmed bile reflux
      gastritis. A gastroscopic features in bile reflux gastritis are: presence of bile
      and incrustation in the stomach mucosae a crystals bile, and co-existence changes
      mucosa: a hyperaemia, fragility and errosiones. Characteristics subjective
      sufferings are: feeling a rancid fat in the throats (100%), intolerance of the
      milk (92%) and bile vomit.

PMID- 9770994
TI  - [Frequency of Helicobacter pylori infection depending on morphological changes in
      gastric mucosa in patients over 65 years of age].
AB  - In older patients involution processes are observed. Frequency of H. pylori
      infection has been related of histopathological changes of gastric mucosa in
      patients over 65 yrs old. In 73% of analyzed patients gastritis atrophica has
      been documented.

PMID- 9770995
TI  - [Duodenogastric reflux in patients with irritable bowel syndrome treated with
      wheat bran].
AB  - The aim of this study was to estimate the influence wheat bran enriched diet on
      incidence of duodenogastric reflux and symptoms in patients suffering from
      irritable bowel syndrome with predominant constipation. Duodenogastric reflux was
      examined in 31 patients by means of the cholangioscintigraphy. The results of
      this investigation were compared with the symptom score before and after 12 weeks
      of treatment with wheat bran. The incidence of duodenogastric reflux was not
      decreased post bran consumption. Bowel dysfunction symptom score was
      significantly lower in both subgroups-with and without duodenogastric reflux.
      However dyspeptic symptom score was not significantly lower in these groups.

PMID- 9770996
TI  - [Acute radiation reaction and its healing time after skin cancer radiotherapy in
      elderly patients].
AB  - In group of 106 patients over 70 with skin cancer radiation-induced reaction and
      its healing time were evaluated. Mean age was 78.3 years. The control group
      consisted of 35 patients under 70 with average age 59 years. All patients were
      treated under conventional roentgenotherapy conditions with dose fractionation.
      Intensification of acute radioreaction was classified according to RTGO and EORTC
      scores. In elderly patients the first grade of reaction was twice lower than in
      control group. Average healing time of radiation-induced reaction in the whole
      elderly group was 3 weeks longer in comparison with controls. Mean healing time
      of the same reaction intensity grade was also longer in elderly. In the first
      grade of changes it was 1 week longer. 3 and 1 week there were in second and
      third degree respectively.

PMID- 9770997
TI  - [The influence of the proper preparation of the female patients with missed labor
      syndrome on the diminishing of the complications after its termination].
AB  - During the period of 6 and half years the cases of 175 patients with missed
      labour were analysed in Gynaecology--Obstetric Ward of the City Hospital in
      Tarnow. Laboratory and clinical being--well of a pregnant woman with missed
      labour syndrome does not exclude the possibility of complications among the
      patients who have not been prepared. The introduced method made it possible to
      eliminate such complications as deaths, hemorrhages, clotting disturbances and
      infections. The period of hospitalization has become evidently shorter.

PMID- 9770998
TI  - [Testosterone response (in blood serum and seminal plasma) to anti-estrogen
      stimulation test in fertile men and patients with disturbances of
      spermatogenesis].
AB  - Testosterone concentrations in blood serum and seminal plasma in basic conditions
      and in antiestrogen test (Clostilbegyt 100 mg daily for 10 days) were evaluated
      for 21 fertile males, 24 males with normogonadotropic oligozoospermia and 25
      azoospermia patients. Average output testosterone concentration in blood serum of
      the analysed groups did not differ statistically significantly, but in
      antiestrogen test it increased statistically significantly. Average output
      testosterone concentration in semen plasma in fertile men was 0.66 +/- 0.26 ng/ml
      (about 10 times lower than in blood serum) and idiopatic oligozoospermic patients
      had a half of this number. Clostilbegyt test caused increase of testosterone
      concentration in semen plasma in all groups (except for normospermic) what proves
      the relation of hormonal reactions observed in blood serum with the ones in semen
      plasma.

PMID- 9770999
TI  - [Seasonal fluctuation in peptic ulcer occurrence: a disappearing phenomenon?].
AB  - Some studies suggest that seasonal fluctation of peptic ulcer occurrence is not
      common these days. The retrospective analysis of 4858 endoscopies performed in
      Srodmiejski Hospital in Warsaw confirmed this conclusion. There is no significant
      differences in frequency of peptic ulcer occurrence in particular seasons.

PMID- 9771000
TI  - [Atypical case of retroperitoneal paraganglioma parasympaticum coexisting with
      recurrent bleeding from upper gastrointestinal tract].
AB  - The authors report a case of 47 years old male who was treated for 1,5 year
      because of recurrent bleedings from upper GIT. Performed examinations showed the
      presence of retroperitoneal paraganglioma parasympaticum with multiple metastases
      in bones. A Zollinger-Ellison syndrome was suspected. The final correct diagnosis
      was established at last microscopically after surgical excision of the specimens.

PMID- 9771001
TI  - [A case of cervical pregnancy diagnosed by laparotomy and photographically
      documented].
AB  - A case deals with 33 years old primipara in the last stage of the first trimenom
      of pregnancy. To dispel the doubts connected with development of pregnancy and
      ultrasound assessments the explorative laparotomy was undertaken. The cervical
      pregnancy was stated. The curettage and tamponing of the cervical canal failed.
      The procedure was completed with hysterectomy without adnexa. The advantage of
      early laparotomy consisted in getting a clear view of the situation and giving
      the maximum of safety to the patient when the attempts to save the uterus were
      being carried out. The early laparotomy made it possible to take some unique
      photographs of the uterus "in situ" with cervical pregnancy.

PMID- 9771002
TI  - [Actively continued twin pregnancy with intrauterine death of one fetus].
AB  - A case of twin pregnancy with intrauterine death of one fetus in the 28 th week
      of pregnancy been described. The pregnancy was actively continued. The following
      procedure was introduced: 1. Tocolysis, 2. Drugs accelerating lung maturation of
      the alive fetus, 3. Antinfectious and anticoagulopathy prophylaxis, 4. Special
      care of the mother and the alive fetus. In the 30 th week of pregnancy spontaneus
      labor occurred "per via naturales". The macerated dead fetus and the alive
      premature newborn were born. The baby was charged home in good condition in the
      45 th day after delivery.

PMID- 9771003
TI  - [Henoch-Schoenlein purpura and toxocarosis].
AB  - Henoch-Schoenlein purpura is a common vasculitic syndrome in childhood. Diagnosis
      is based on the presence of nonthrombocytopenic purpura arthritis or arthralgia,
      abdominal pain and glomerulonephritis. In our case report a causal relationship
      between toxocarosis and Henoch-Schoenlein purpura is suggested.

PMID- 9771004
TI  - [Achalasia of the esophagus].
AB  - In this review achalasia of the esophagus is presented. Attention is drawn to the
      prevalence, pathology, symptomatology, diagnostic procedures and several
      treatment options.

PMID- 9771005
TI  - [Postoperative monitoring of patients with gastric cancer].
AB  - The problem of monitoring of patients after radical treatment because of gastric
      cancer is discussed. The purpose of postoperative follow-up is diagnosis of
      metastases or recurrence by means anamnesis, physical examination, laboratory
      studies, biochemical markers, double contrast x-ray, chest x-ray, CT scan, USG
      and gastroscopy.

PMID- 9771006
TI  - [Myocutaneous flaps: some remarks on genesis of the method].
AB  - A history, actual development and clinical applications of a new plastic
      operation with myocutareous flaps are discussed.

PMID- 9771007
TI  - [Differential diagnosis mistakes in carpal tunnel syndrome and their
      therapeutical consequences].
AB  - Analysis of some diagnostic mistakes in carpal tunnel syndrome has been discussed
      in relation to similar symptoms.

PMID- 9771008
TI  - [Erythropoietin and hypertension].
AB  - Hypertension is one of the adverse effects associated with recombinant human
      erythropoietin (rHuEPO) therapy for anaemia in hemodialysed patients. The
      incidence of hypertension is reported to be 10-15%. The exact mechanism of rHuEPO
      induced hypertension has not been fully elucidated, although in this paper
      several theories have been presented.

PMID- 9771009
TI  - [The evaluation of surgical revascularization of the left ventricular systolic
      function after surgery].
AB  - To determine the effects of coronary artery bypass grafting (CABG) on the left
      ventricular function the 83 patients aged 52 +/- 6 years with ischaemic heart
      disease were examined by a standard two dimensional echocardiography (ECHO) and
      exercise test (EXT) before CABG and 1, 3, 6, 12 month after CABG. The following
      parameters were measured: LV ejection fraction (LVEF) and wall motion score index
      (WMSI) according to 14-segmental model and the duration of exercise test with
      work load. In conclusion, in patients surgical revascularization can
      significantly improve left ventricular function 6 and 12 month after CABG. We
      didn't observe connection between left ventricular function and result of
      exercise-test.

PMID- 9771010
TI  - [Recording of atrial and ventricular signal averaged ECGs in patients with mitral
      valve prolapse syndrome].
AB  - The aim of the study was to assess the time-domain parameters of atrial signal
      averaged ECG (ASAECG) and ventricular signal-averaged ECG (SAECG) in patients
      with mitral valve prolapse (MVP) and healthy ones. Fifty patients with MVP (15
      men, 35 women, mean age--37.1 +/- 8.9 years) and 50 healthy controls (36 men, 14
      women, mean age 38.2 +/- 4.7 years) were studied). The following time-domain
      parameters of ASAECG were analysed: the root mean square voltage of the terminal
      10, 20, 30 ms of filtered P wave (RMS10, 20, 30) and the total duration of
      filtered P wave (PWD). The atrial late potentials (ALP) were defined as the
      presence: RMS10 < 4 microV i PWD > 123 ms. As the time-domain parameters of SAECG
      we analysed: the root mean square voltage of the terminal 40, 50 ms of the
      filtered QRS (RMS 40, 50), the total filtered QRS duration (t-QRS) and the low
      amplitude signal duration < 40 microV in the terminal QRS (LPD). The ventricular
      late potentials (VLP) were defined as the presence of at least two of the
      following criteria: t-QRS > 114 ms, RMS 40 < 20 microV i LPD > 38 ms. There was
      no difference in the time-domain parameters of ASAECG between patients with MVP
      and controls: RMS 10: 4.5 +/- 1.8 microV vs 4.8 +/- 1.9 microV, RMS 20: 6.3 +/-
      2.2 microV vs 6.1 +/- 2.2 microV, RMS 30: 8.3 +/- 2.5 microV vs 7.1 +/- 2.7
      microV and PWD 113 +/- 11.7 ms vs 116 +/- 15.2 ms, respectively. Three patients
      with MVP (6%) and 5 controls (10%) revealed ALP. THE time-domain parameters of
      SAECG did not differ in patients with MVP and controls: RMS 40: 40.2 +/- 29.1,
      microV vs 35.5 +/- 18.2 microV, RMS 50: 68.2 +/- 40.1 microV vs 64.4 +/- 33.6
      microV and t-QRS-101.4 +/- 10.7 ms vs 101.8 +/- 10.9 ms i LPD--28.7 +/- 10.0 ms
      vs 28.3 +/- 10.0 ms, respectively. VLP were found in 7 patients with MVP (14%)
      and 5 controls (10%). Our findings suggest that time-domain parameters of ASAECG
      and SAECG could not differentiate patients with MVP and healthy ones. Moreover,
      the presence of ALP and VLP in MVP group did not correlate with supraventricular
      and ventricular arrhythmias recorded on ambulatory ECG.

PMID- 9771012
TI  - [Time of occurrence of paroxysmal atrial fibrillation in Holter monitoring in
      patients with coronary heart disease and in patients with hypertension].
AB  - Paroxysmal atrial fibrillation (PAF) often accompany coronary heart disease
      (CHD), and primary hypertension (PH). The aim of the study was to evaluate the
      time of occurrence and duration of paroxysmal atrial fibrillation (PAF)
      identified from Holter recordings in 63 patients (27 women and 36 men) with CHD
      (n = 45) and PH (n = 18). No pharmacological treatment was applied before and
      during the examination. All patients were in sinus rhythm at the start and the
      end of the recording which lasted for 24 hours. PAF were defined as the
      occurrence of at least four beats of supraventricular origin, with no visible P
      or flutter waves. The time of onset, duration, ventricular rate and symptoms of
      each PAF were noted. There were 219 paroxysms recorded in 63 patients which
      occurred more often by day than by night, the time of duration was 0.9-240 s. Of
      the total, 16.3% of episodes with CHD and 9.5% episodes in patients with PH
      occurred between the hours 8:00-10:00 and between 16:00 and 18:00; 9.1% and 21%
      respectively. We concluded that in patients with CHD and with H most of the
      episodes (95%) are silent, they occurred more often during the day activity
      (particularly between the hours of 8:00 and 10:00 and 16:00-18:00 in both
      groups). In patients with CHD we observed the third peak of occurrence of PAF
      between the hours 22:00-0:00.

PMID- 9771011
TI  - [The evaluation of carcinoembryonic antigen determination in the pericardial
      fluid in the diagnosis of the cause of pericarditis].
AB  - Pericardial fluid CEA level was measured with radioimmunoassay in 19 patients
      with large pericardial effusion of unknown origin. In 11 patients malignancy was
      diagnosed. In all of these patients pericardial fluid CEA levels were above 7
      ng/ml (mean value 52.6 +/- 42.6 ng/ml). In 8 patients the etiology of
      pericarditis was non-malignant. In all of them pericardial fluid CEA levels were
      below 7 ng/ml (mean value 2.2 +/- 1.6 ng/ml). In 9 patients with malignant
      pericarditis serum CEA levels were also determined: they were found to be lower
      than pericardial fluid CEA values in 6 patients. It was concluded that
      pericardial fluid CEA elevation is a reliable criteria of neoplastic pericardial
      involvement.

PMID- 9771013
TI  - [The values of selected lipid parameters and atrial pressure in persons with
      hyperinsulinemia and normal glucose tolerance].
AB  - In 60 healthy non-obese persons we determined fasting plasma insulin
      concentrations. Afterwards we performed test with oral load with 75 g glucose. We
      determined plasma concentration of insulin one hour and two hours after this
      load; we found that 14 of 60 subjects had hyperinsulinemia with normal glucose
      tolerance. In the group of persons with hyperinsulinaemia we have shown the
      increase of fasting plasma triglyceride levels and elevated diastolic blood
      pressure. We suggested that healthy persons with hyperinsulinemia and normal
      glucose tolerance have an increase risk for cardiovascular diseases.

PMID- 9771014
TI  - [The influence of 3-month treatment with molsidomine on structure, function and
      some neurohormonal parameters in patients with chronic heart failure treated with
      digoxin, diuretic and angiotensin converting enzyme inhibitors].
AB  - The aim of the study was to estimate the influence of long-term treatment with
      molsidomine on structure, systolic function and neurohormonal parameters in
      patients with chronic heart failure (CHF). Investigations were carried out in 30
      patients (mean age 63.0 +/- 10.9) in NYHA class III and IV. The cause of CHF was:
      coronary artery disease in 60% of patients, hypertension in 20% and dilated
      cardiomyopathy in 20% of patients. Molsidomine was administrated in dose of 2 mg
      tid for 3 months. During the study the previous treatment with ACEI, diuretics
      and digitalis was maintained. Using echocardiographic method left atrial
      dimension (LA), left ventricular end diastolic (LVEDD) and end systolic diameter
      (LVESD), interventricular septum (IVSDD) and posterior wall end diastolic
      diameter (LVPWDD), ejection fraction (LVEF) and fraction of shortening (LVFS)
      were measured. Plasma level of atrial natriuretic peptide, endotelin,
      neuropeptide Y and aldosterone and plasma renin activity were estimated
      radioimmunologically. All echocardiographic and neurohormonal measures were
      performed 4 times: before therapy, after 3 days, 2 weeks and 3 months of
      treatment with molsidomine. We observed significant increase in LVEF, which at
      baseline was 33.8% and after 3 months 44.8% (p < 0.05). None of the other
      echocardiographic parameters nor any of neurohormonal factors changed
      significantly during the 3-months treatment with molsidomine.

PMID- 9771015
TI  - [The influence of 5-week relaxation therapy on arterial blood pressure in
      patients with borderline hypertension].
AB  - The present study was performed to evaluate the influence of 5-week relaxation
      therapy on office and ambulatory blood pressure in young borderline
      hypertensives. Thirty patients were studied. The office blood pressure decreased
      significantly after 5 weeks of relaxation therapy (P < 0.001 for both systolic
      and diastolic blood pressure). Ambulatory monitoring revealed only a slight
      decrease of 24-hour blood pressure (P = 0.02). Our results indicate limited
      efficacy of relaxation therapy in treatment of borderline hypertensives.

PMID- 9771016
TI  - [The influence of 5-week relaxation therapy on psychological state of patients
      with borderline hypertension].
AB  - The aim of the present was to evaluate the influence of 5-week relaxation therapy
      on psychic state of patients with borderline hypertension. The study group
      consisted of 30 hypertensives. We observed significant changes in anxiety scale,
      defensiveness, self-confidence, intraception, nurturance, affiliation,
      heterosexuality, change and succorance scales. In conclusion, 5-week relaxation
      changes significantly psychological status of patients with borderline
      hypertension.

PMID- 9771017
TI  - [The natural history study of 208 patients with atherosclerosis of the lower
      extremities and diabetes mellitus].
AB  - Analysis of 208 patients with atherosclerosis of the lower extremities and co
      existing diabetes mellitus was performed to document actual symptoms, to propose
      a classification of extremity ischemic to localisate atherosclerotic changes and
      to evaluate therapeutic methods and their results. Authors suggest that to
      improve therapeutic results in this group of patients necessary is as follows:
      (a) early diagnosis of atherosclerotic ischemia of extremities, (b) proper
      preparing to revascularization, (c) early reconstruction of ischemic vessels, (d)
      good specialist controls in after surgery period.

PMID- 9771018
TI  - [False aneurysms of lower extremity arteries: noninvasive preop diagnosis with
      magnetic resonance angiography and Doppler ultrasonography].
AB  - The purpose of this study was to work out a diagnostic algorithm to be used in
      patients surgically treated because of a false aneurysm of arteries supplying the
      lower limb. The study includes preoperative vessel evaluation as well as
      treatment results assessment with MRA and US methods. Examinations included until
      now 16 patients with clinical false aneurysm suspicion. Most cases presented
      false aneurysms being complications after arterial graft implantation, in two
      patients, who were not previously operated, diagnosed false aneurysms were the
      result of injury. We performed 23 examinations (7 of which were postoperative
      treatment result evaluation examinations). Examinations were performed on MR
      equipment with a 1.5 T field induction. The 2D TOF with traveling presaturation
      method was used. Primary data and reconstructed (MIP) angiograms were analyzed by
      a radiologist having no access to clinical information and previous examination
      results. Ultrasound duplex doppler examinations were performed with 7 MHz linear
      probe. The MRA examinations visualized 7 false aneurysms of the lower Y-graft
      junction. Clinical verification, ultrasonography examinations and surgery
      confirmed the existence of 6 aneurysms of the Y-graft as well as 5 out of 6
      diagnosed in the ileofemoral graft junctions area. The post-traumatic aorta
      aneurysm and the postarteriographic femoral aneurysm were also confirmed. Two
      false positive MRA diagnoses were due to dilatation of the artery below the graft
      junction, in one case it was a dilatation of the vessel below a stenosis.
      Furthermore, the MRA helped diagnosing stenoses and occlusions in femoral
      arteries and common iliac artery.

PMID- 9771019
TI  - [Implantation of bifurcated aorto-femoral vessel prosthesis in patient after
      myocardial infarction].
AB  - A case of 44-year old man admitted to Surgery Dept. Because Leriche syndrome was
      described. Three months earlier patient was treated because of severe myocardial
      infarction complicated with shock and cardiac arrest. During actual
      hospitalisation bifurcated aorto-femoral vessel prosthesis was implanted with
      good clinical result.

PMID- 9771020
TI  - [Pharmacological treatment of restenosis after coronary angioplasty and bypass
      grafting].
AB  - Angioplasty and bypass surgery have become standard methods of treating patients
      with symptomatic coronary atherosclerosis but restenosis remains the major
      limitation of percutaneous coronary revascularization. In pharmacological
      management of restenosis after coronary intervention multiple agents have been
      tried, with mostly discouraging results. Aspirin, dipyridamole, ticlopidine,
      heparin. Hirudin, and warfarin has failed to show beneficial effects on
      restenosis. Of all antithrombotics, only an inhibitor of the platelet IIb/IIIa
      integrin, which may lead to early vessel changes, leading to decrease restenosis.
      Antiproliferative agent (trapidil and angiopeptin) and probucol have also
      resulted in improved restenosis rate. In patients after bypass surgery with some
      degree of hyperlipidemia intensive lipid-lowering therapy is beneficial in
      slowing the late progressions of atherosclerosis as well as graft occlusion.

PMID- 9771021
TI  - [Lansoprazol ++ : a new proton pump inhibitor].
AB  - Lansoprazole is the new proton pump inhibitor, decreasing the volume of gastric
      acid secretions and inhibiting secretion of gastric acid and pepsin. Lansoprazole
      appears to be more effective in therapy of gastric ulcer and duodenal ulcer in
      comparison with H2-receptor antagonists and omeprasole. Reflux oesophagitis and
      Zollinger-Ellison syndrome are also healed by Lansoprazole. The best results in
      the treatment of patients with peptic ulcer, reflux oesophagitis and Zollinger
      Ellison syndrome were occurred after a daily 30 mg dose of Lansoprazole.
      Treatment of patients with duodenal ulcer should be continued for 2 to 4 week and
      the case of gastric ulcer a well as reflux oesophagitis should be prolonged till
      4 to 8 week. Lansoprazole is well tolerated, reported adverse effects are similar
      to the incidence observed in patients treated with other proton pump inhibitors.

PMID- 9771022
TI  - [Participation of glyoxalases and methylglyoxal in diabetic complication
      development].
AB  - The glyoxalase system catalyses the conversion of methylglyoxal to D-lactate via
      intermediate S-D-lactoylgutathione. This system consists of two enzymes,
      glyoxalase I and glyoxalase II. A link between the development of diabetic
      complications and the glyoxalase system has been suggested at the genetic and
      metabolic level. Insulin-dependent diabetic patients without complications
      (retinopathy, neuropathy) had a significantly higher frequency of the glyoxalase
      phenotype GLO 1-1 than patients with complications. Periodic hyperglycaemia may
      contribute to the development of diabetic complication through methylglyoxal
      mediated changes in protein solubility and aggregation characteristics.

PMID- 9771023
TI  - [Personality assessment in differentiation of myocardial infarction pain in R.B.
      Cattella theory].
AB  - Problem of cardiac pain in patients with myocardial infarction is discussed in
      relation to personality determinations according to R.B. Cattella theory.

PMID- 9771024
TI  - [Main sources of the formation of contingents of tuberculosis patients with drug
      resistant or sensitive Mycobacterium tuberculosis isolates].
AB  - To form contingents of pulmonary tuberculosis patients with isolated drug
      resistant Mycobacteria tuberculosis (MBT) strains, chronic patients having the
      disease for more than 3 years (50.3%) head the list, new cases (36.9%) detected
      in the past 3 years (1994-1996) rank second, next are those with relapsing
      tuberculosis (12.8%) identified in 1994-1996. The ratio of the above group of
      patients with isolated drug-sensitive MBT species is 23.3, 68.8, and 7.9%,
      respectively.

PMID- 9771025
TI  - [Characterization of epidemic foci of tuberculosis and improvement of the follow
      up of children and adolescents from the environment of patients with
      tuberculosis].
AB  - Despite unfavorable socioepidemiological conditions, there are potentials of
      reducing tuberculosis morbidity in the epidemic foci of children and adolescents
      (by more than 3.5 times). For this, all the children and adolescents from the
      foci of infection should be thoroughly examined and followed up and educational
      and preventive measures including intensified antituberculosis propaganda should
      be made in these foci.

PMID- 9771026
TI  - [Social and hygienic problems of tuberculosis in the penal executive system].
AB  - Analyzing the main indices of tuberculosis epidemiology among the convicts showed
      that there is 1 steady-state upward trend of its morbidity, mortality, bacillary
      forms. The latters are characterized by the extent of tuberculosis and its
      severity, which is suggestive of a large infection reservoir among the convicts.
      This is due to deteriorating macro- and microsocial factors, so this situation
      should be considered to be extremely explosive both for the convicts and for the
      general population of the country.

PMID- 9771027
TI  - [Impact of tuberculosis in penal labor facilities on the epidemiological
      situation in the Sverdlovsk region].
AB  - The unfavourable tuberculosis situation in the corrective labour facilities
      affects the main rates of tuberculosis in the region. Presently, the total
      registered cases of tuberculosis among prisoners are 36.7 times as high as those
      in the age-matched general population of the Sverdlovsk Region. The rates of
      relapses, incidence, death due to tuberculosis show 72.0-, 36.1-, and 10.4-fold
      increases, respectively. Almost every 10 persons from the labour corrective
      facilities suffer from active tuberculosis. In the past decade, the growth rates
      of main tuberculosis parameters in the corrective labour facilities were much
      higher (total tuberculosis morbidity by 2.1 times, relapses by 2.1 times, general
      morbidity by 1.7 times, and total tuberculosis mortality by 2.8 times) than those
      in the region's general population. Extrapulmonary tuberculosis was not virtually
      detected in the labour corrective facilities) due to the lack of special
      diagnostic methods.

PMID- 9771028
TI  - [Dynamics of morbidity at health care institutions and penal labor facilities in
      the Udmurt Republic].
AB  - Comparative analysis indicated that morbidity in the corrective labour
      institutions, Ministry Internal Affairs of the Udmurt Republic, is much higher
      than that in the therapeutical-and-prophylactic institutions of the republic. In
      the corrective labour institutions, patients who isolate bacteria and who have
      destructive processes are much more common. The clinical course of clinical
      tuberculosis is noted to be aggravated, there is an increase in the incidence of
      caseous pneumonia.

PMID- 9771029
TI  - [Epidemiologic monitoring of tuberculosis in Omsk].
AB  - The paper presents an epidemiological monitoring of tuberculosis infection with
      personal computers. The procedure may standardize different epidemiological
      characteristics, objectively evaluate the level of antituberculosis work in
      various areas, promptly process a great deal of data. The tuberculosis
      epidemiological situation in Omsk is analyzed in comparison with the indices of
      epidemiological well-being.

PMID- 9771030
TI  - [Clinical and epidemiological aspects of controlled short-term chemotherapy].
AB  - The current aspects of controlled short-term chemotherapy are reviewed. The
      efficiency and mechanism of action of various agents are evaluated, with emphasis
      laid on their effects of mycobacterial population, including drug-resistant
      Mycobacteria tuberculosis. Treatment of new cases isolating M. tuberculosis is
      shown to be a priority under the present epidemiological conditions, which
      stopped the spread of infection in the human community and reduces the infection
      and disease rates. The programmes of controlled chemotherapy in different
      patients recommended by the WHO and the International Tuberculosis and Pulmonary
      Diseases Control Union are analyzed. This leads to the conclusion that the
      programmed chemotherapy with clear identification of groups of patients and well
      defined drug combinations, the fixed duration of treatment and the calculated
      required doses for therapy can drastically reduce tuberculosis morbidity and
      mortality rates drastically.

PMID- 9771032
TI  - [Incidence and pattern of recurrent side effects in persons with different
      haptoglobin phenotypes during chemotherapy of pulmonary tuberculosis].
AB  - A total of 197 patients with pulmonary tuberculosis who had different haptoglobin
      phenotypes (Hp) were examined. Antituberculous agents were found to cause side
      effects in 145 patients during chemotherapy. In 82.7% of cases, adverse reactions
      occurred in patients with Hp 2-2 and Hp 1-1. Relapsing adverse reactions occurred
      mainly as allergic skin reaction and mixed syndrome. In 89% of cases, the pattern
      of relapsing adverse reactions did not coincide with the initial manifestations.

PMID- 9771031
TI  - [Treatment of newly diagnosed patients with infiltrative and disseminated
      pulmonary tuberculosis].
AB  - To enhance the efficiency of treatment in new cases of infiltrative and
      disseminated destructive pulmonary tuberculosis, an intermittent (twice daily)
      regimen of intravenous dropwise administration of three drugs (isoniazid,
      rifampicin, PASK) was proposed. The immediate results of clinical observations
      suggest that intermittent 3-drug intravenous chemotherapy supplemented by
      collapse therapy in some indicated cases, provides a high control over the
      therapy, sparing drug load, good tolerance, and rather high efficiency:
      elimination of destructions in 81.4% (mean 4.2 months), cessation of bacterial
      isolation in 88.9% in the early (2.2 months) period.

PMID- 9771033
TI  - [Contingents of young children at a specialized hospital].
AB  - The case histories of 80 children aged 0-3 years with varying primary
      tuberculosis who were treated at the Pediatric Specialized Unit in 1990-1995 are
      analyzed Specific intrathoracic lymph nodal lesions (33.75%) were more common in
      the pattern of clinical tuberculosis, the primary tuberculosis complex being 2
      times less. A third of children had a complicated course of local types of
      tuberculosis. In ill infants, the causes of primary tuberculosis were no BCG
      vaccination, familial tuberculosis contact, and infrequent use of specific
      chemotherapy.

PMID- 9771034
TI  - [A new method of thoracic radiography, an alternative to fluorography].

PMID- 9771035
TI  - [Effects of low-intensity laser irradiation on hormonal responsiveness of
      patients with pulmonary tuberculosis].
AB  - To examine the impact of low-intensive laser radiation (LILR) on endocrine
      function in patients with pulmonary tuberculosis, the time course of blood levels
      of thyroid hormones, cortisol, and insulin was studied in 117 patients of whom 64
      received complex treatment by using LILR. Pulmonary tuberculosis was ascertained
      to be characterized by a marked hormonal imbalance, including impaired metabolism
      of thyroid hormones, hypercorticism, altered pancreatic incretion, which
      negatively affects the efficiency of antituberculosis therapy. Intravenous and
      epicutaneous therapy promotes recovery of endocrine responsiveness and enhances
      the efficiency of treatment in patients with pulmonary tuberculosis.

PMID- 9771036
TI  - [Methods of treatment of postoperative residual cavities (empyemas) and bronchial
      fistulas in patients with pulmonary tuberculosis].
AB  - Two new methods for elimination of bronchial fistulas in postresectional empyemas
      were tested in 40 patients. The most effective procedure was transbronchial
      diathermocoagulation of the draining (fistular) bronchus, with a full clinical
      effect being in 100% of patients), and selective foam rubber obturation in 80%.

PMID- 9771037
TI  - [New approaches to the evaluation of pulmonary circulation in surgical patients
      with tuberculosis].
AB  - Prior to and following surgery, 70 patients were examined for pulmonary
      tuberculosis who were divided into 2 groups: 1) 27 patients with limited
      processes (tuberculomas, infiltrating, cavernous tuberculosis in 1-2 segments)
      and 2) 43 patients with disseminated tuberculosis in 4 lobes or more. A
      comprehensive examination including studies of pulmonary circulation by
      radiotracer techniques (scanning, scintigraphy) and an original contactless study
      of pulmonary circulation (CSPC). There was a correlation between the results
      obtained by the two methods. The findings indicate a high validity of CSPC6 which
      makes it possible to recommend it as a screening technique for detection of
      pulmonary circulatory disorders.

PMID- 9771038
TI  - [Pathomorphosis of tuberculosis in children of early and preschool age (autopsy
      data)].
AB  - A total of 339 protocols of autopsies of babies infants, and pre-school children
      within 50 year (1947-1996) are analyzed. As compared with 1947-1956, in the past
      3 decades the autopsies showed 14.6-, 35.7-, and 79.7-fold reductions in babies,
      infants, and preschool children, respectively. However, the past 5 years is
      marked by a reversal of more severe tuberculosis in children under 3 years, which
      necessitates to intensify social, prophylactic, and therapeutical
      antituberculosis measures among children.

PMID- 9771039
TI  - [Sensitivity and specificity of polymerase chain reaction based test in the
      diagnosis of peripheral lymph node tuberculosis].

PMID- 9771040
TI  - [In vitro study of the modulating effect of antitubercular agents on the rosette
      formation response in patients with pulmonary tuberculosis].
AB  - The wide medical application of new highly active antituberculous agents (ATA)
      having a definite mechanism of action on immunological homeostasis makes
      pharmacological regulation of immunological responses real in patients with
      pulmonary tuberculosis. The purpose of this study was to examine the effect of
      major ATA on the body's immunological responsiveness in vitro, i.e. by the
      changes in E-RFC used as a loading test, their immunoactive properties were
      examined with and without addition of ATA. The study provided a new
      methodological approach which may help in more effectively determining the nature
      of effects of the study ATA on the qualitative and quantitative parameters of the
      T system, in clarifying whether ATA have certain immunoregulating properties, and
      in quantitatively defining the magnitude of their expression. The used parameter
      E-RFC is an adequate test for studying the immunoactive properties of ATA acting
      primarily on cell immunity. Thus, this offers scope in practical medicine for
      goal-oriented regulation of an immune response in different tuberculosis
      infections by using appropriate ATA.

PMID- 9771041
TI  - [Pathogenetic aspect of the diagnosis of tuberculous lymphadenitis].
AB  - Based on their own experimental (55 rabbits) and clinical (114 patients)
      findings, the authors propose a new immunopathogenetic approach to diagnosing
      tuberculous lymphadenitis under the present-day conditions by taking into account
      the environmental situation. They describe an original enzyme immunoassay for
      lymph nodal extracts, which has yielded positive results: 88% sensitivity, 92%
      specificity, and 90% diagnostic efficiency.

PMID- 9771043
TI  - [Differential diagnosis significance of measuring surfactant phospholipid levels
      in lung diseases].
AB  - The levels of surfactant phospholipid from bronchoalveolar lavage were measured
      in 70 patients with pulmonary diseases and in 10 apparently healthy individuals.
      The levels of surfactant phospholipid components were lower in patients with
      peripheral lung cancer, infiltrative tuberculosis, focal pneumonia, most
      significant in cancer; differential diagnostic criteria for these diseases are
      defined.

PMID- 9771042
TI  - [Antibiotic sensitivity of pathogenic microflora: data of the bacteriological
      laboratory at the antituberculosis clinic].
AB  - A total of 426 cultures for nonspecific organisms, made at the Bacteriological
      Laboratory of the Antituberculosis Dispensary, were analyzed. Escherichia coli,
      Streptococcus pyogenes, and Staphylococcus aureus were most common among the
      isolated pathogens. Evaluation of antibiotic sensitivity by using the disks
      showed augmentin, cefuroxime axetil, and ciprofloxacin to be most effective.
      Streptomycin and rifampicin resistance of pathogens was highest. In patients with
      tuberculosis, the non-tuberculosis flora showed resistance to the drugs widely
      used in general practice (ampicillin, carbenicillin, oxacillin, lincomycin,
      erythromycin). Among macrolides, rovamycin was more effective than erythromycin.
      It is concluded that when wide-spectrum antibiotics are prescribed, new and
      potent drugs should be used in a tuberculosis hospital.

PMID- 9771044
TI  - [Inhibitory effects of electric UHF field and magnetic infrared laser irradiation
      on Mycobacterium tuberculosis].
AB  - Microbiological studies indicate that stimulating the multiplication of
      Mycobacteria tuberculosis, electric UHF fields at 40 and 70 W make them available
      for drug exposure despite drug resistance. Unlike the electric UHF fields, MILI
      has a direct inhibitory effect on Mycobacteria tuberculosis that are sensitive
      and resistant to antibiotic drugs, by potentiating their action. In the clinical
      setting, chemotherapy in combination with electric UHF fields and MILI therapy
      reduces the time of disappearance of clinical signs of the disease, infiltration
      resolution, bacterial isolation, and decay cavity closure.

PMID- 9771045
TI  - [Effects of tobacco smoke condensate on the culture and biochemical properties of
      Mycobacterium tuberculosis].

PMID- 9771046
TI  - [Effects of coal tar on hematological parameters in experimental tuberculosis].
AB  - Guinea pigs were injected with coal tar (CT) (intratracheally, 25 mg per animal
      once a week or a month for 2 or 8 months, respectively), then they were infected
      with MBT (H37Rv, 0.1 mg, subcutaneously). There were changes in hematological
      responses to MBT changes (in the context of the cell composition of bone marrow
      and peripheral blood), their pattern was associated with the mode of exposure to
      CT preceding MBT inoculation. The greatest differences were found in the
      responses of bone marrow lymphopoiesis and peripheral lymphocytes upon both
      exposures to CT. On greater exposure to CT (once a week) the changes in the blood
      system indicated that CT had an adverse effect on the course of experimental
      tuberculosis, while on lesser exposure (once a month), the effect of CT was more
      favourable.

PMID- 9771047
TI  - [New methods of the surgical treatment of bronchial asthma].

PMID- 9771048
TI  - [Development of peripheral lung cancer from tuberculoma capsule].

PMID- 9771049
TI  - [A case of tuberculosis associated with pulmonary sequestration].

PMID- 9771050
TI  - [Biocompatibility--the compatibility between a technical and a biological
      system].

PMID- 9771051
TI  - [The effects of tooth loss on the anatomy of the maxilla].

PMID- 9771052
TI  - [Sports medicine].

PMID- 9771053
TI  - [Does psychosocial intervention in cancer patients affect survival and
      psychological well-being?].
AB  - We have critically reviewed the scientific literature examining the effect of
      psychosocial interventions on survival and well-being among adult cancer
      patients. Only studies using randomization and including a control-group not
      receiving psychosocial intervention were reviewed. Six studies examined the
      effect on prognosis. In four of these studies survival increased significantly in
      the intervention group as compared to the control group. All of these studies,
      however, have methodological flaws, leaving a possible prognostic effect to be
      clarified in larger, well-controlled future studies. The effect of psychosocial
      intervention on various psychosocial variables (such as anxiety and depression)
      was evaluated in 20 studies. Differences in patient populations, intervention
      strategies, and outcomes decrease the comparability of the results, and the
      majority of these studies suffer from methodological flaws as well. A positive
      effect on anxiety and depression immediately following the intervention is,
      however, reported in the majority of these studies. It is thus possible that the
      level of anxiety and depression may be decreased by integrating psychosocial
      intervention in the overall treatment of cancer.

PMID- 9771054
TI  - [Chemotherapy and radiotherapy as part of curative management of esophageal
      cancer].
AB  - Chemotherapy and irradiation it combination or alone have been employed in the
      treatment of oesophageal carcinomas for many years. However, their place in
      curative treatment is not definitively clarified. Several non-randomized studies
      indicate an effect from combined chemotherapy and irradiation possibly followed
      by surgery. Randomized studies published during the last few years confirm an
      increased curability in patients who have received combined treatment. New
      multicentre trials show that a more aggressive attitude is indicated in selected
      groups of patients with oesophageal carcinoma. Due to the variable spectrum of
      the disease and complexity of the treatment the treatment should be given in
      centres which master the different modalities.

PMID- 9771055
TI  - [Severely traumatized patients admitted to Aarhus Community Hospital 1994-1995].
AB  - In Denmark, only few studies have addressed the problem of severe trauma. In
      relation to establishing a trauma manual at our hospital we studied trauma
      patients requiring immediate anaesthesiological assistance. Patients from the
      preceeding years, 1994-1995 were identified. The injuries were scored according
      to the Abbreviated Injury Scale (AIS), and Injury Severity Scores (ISS) were
      calculated. Two hundred and fifty-eight trauma patients were identified, 132 of
      these were severely injured, defined as having ISS > or = 15. Of these, 75
      patients were multitraumatised, defined as AIS > or = 3 in at least two regions.
      None of the patients with ISS < or = 15 died. Mortality was 49% among severely
      injured but not multitraumatised patients, while mortality was 56% among the
      multitraumatised patients. Head injuries were the most frequently found severe
      injury (AIS > or = 3), followed by injuries to the thorax and extremities. The
      anaesthesiologist and the orthopaedic surgeon were involved in initial diagnosis
      and treatment in all patients, and beyond these a variety of medical specialties
      were involved. In the light of this study we have revised our procedures and
      registration concerning severe trauma patients.

PMID- 9771056
TI  - [Laparoscopic adrenalectomy. An alternative to open surgery of minor adrenal
      tumors].
AB  - In the period February 1994 to November 1995 11 laparoscopic adrenalectomies were
      performed at our institution (seven women, four men). A transperitoneal approach
      was used in both right- and left-sided operations. Results were collected
      retrospectively. Indications for surgery were: Conn's syndrome (four), Cushing's
      syndrome (two), phaecromocytoma (four), and incidentaloma (one). The operations
      took median 170 minutes (range 105-250 minutes). Median size of the tumour was 4
      cm range 1(1/2)-5 cm). No significant peri- or postoperative complications were
      recorded. The patients were discharged from the surgical unit median two days
      after surgery. Laparoscopic operation emerges as an alternative to open operation
      when dealing with smaller adrenal tumours. Because of the small number of
      patients, these operations have to be restricted to a few centres where both
      internists, anaesthesiologists and surgeons with expertise in this field are
      found.

PMID- 9771057
TI  - [Inflammatory bowel diseases in children].
AB  - From an incidence cohort diagnosed during 1962-1987 we identified all patients
      with onset of IBD before the age of 15 in order to describe the course and to
      compare course and prognosis with adult onset IBD. The mean incidence of IBD
      among children below 15 years was 2.2/10(5), 2.0 for ulcerative colitis (UC), and
      0.2 for Crohns disease (CD). At diagnosis, UC children had more extensive disease
      compared to adults (p < 0.05). Abdominal pains were also more frequent. The
      cumulative colectomy probability was 6% after one year and 29% after 20 years,
      not different from adults. Regarding disease activity, it was found that 60-70%
      of UC patients were in remission in the first 10 years of disease, for CD about
      50% were in remission. One UC patient developed carcinoma of the sigmoid colon.
      Time between onset and development of carcinoma was 12 years. For CD no
      differences in clinical appearance at diagnosis and course between children and
      adults were found. No deaths occurred among CD patients. Three CD patients were
      found to have severe growth retardation already at diagnosis. In conclusion, the
      incidence of IBD is low in childhood. At diagnosis children with UC have more
      widespread disease than adults. Children with CD do not differ in clinical
      presentation, course or prognosis compared to adult onset CD. However, growth
      retardation is a problem among CD patients.

PMID- 9771058
TI  - [Zone therapy of children with nocturnal enuresis].
AB  - The purpose of the study was to clarify whether reflexology is a relevant
      treatment for enuresis nocturna, and to test a research design applicable to
      controlled experiments with reflexology. An unblinded method was used comparing a
      treatment group (1) receiving reflexology to a non-treatment group (2) keeping
      the same record of symptoms. At the start of the study, the volumes of night
      urine in the two groups were comparable. By the end of the study, there was no
      significant decrease in the volume of night urine in either of the groups. Two
      children in the treatment group and one in the non-treatment group became dry
      during the night in the course of the study. In conclusion, reflexology given as
      14 treatment sessions over a period of four months did not result in a
      significant fall in enuresis nocturna in children aged seven to eleven years old.
      It must be concluded that the treatment result can not be distinguished from the
      conditions in the non-treatment group even though the average night diuresis in
      group one showed a slightly decreasing tendency while morning diuresis increased,
      in contrast to group two which exhibited a slight increase in night diuresis. As
      the total diuresis remained constant, this could be interpreted as an increased
      urinary bladder capacity, but in both cases the changes were far from
      significant.

PMID- 9771060
TI  - [Perinatal Campylobacter jejuni infection after Cesarean section].
AB  - A 23 year old woman was admitted for delivery after having experienced a few
      episodes of loose stools. Following an unsuccessful vacuum-extraction, a
      Caesarean section was performed 12 hours after the membranes had ruptured. Thirty
      six hours after the operation, the woman developed fever, and Campylobacter
      jejuni was isolated from her blood. Subsequently, Campylobacter was also
      recovered from the faeces of both mother and child. Though it is likely, that the
      Campylobacter was introduced to the uterus after rupture of the membranes, a
      transplacental infection can not be ruled out.

PMID- 9771059
TI  - [Pretreatment with prednisolone enhances the effect of human lymphoblastoid
      interferon in chronic hepatitis B].
AB  - Patients (n = 213) with chronic hepatitis B were randomised to prednisolone (two
      weeks of 0.6 mg/kg/day, one week of 0.45 mg/kg/day and one week of 0.25
      mg/kg/day) or placebo followed by two weeks rest, and were then given human
      lymphoblastoid interferon 10 MU daily for five days followed by 10 MU thrice
      weekly for 11 weeks. There were statistically significant effects of prednisolone
      pre-treatment on both HBeAg disappearance and HBeAg to anti-HBe seroconversion
      (log rank test statistics 5.43; p = 0.02 and 4.75; p = 0.03). HBeAg disappearance
      and HBeAg to anti-HBe seroconversion rates were 28 vs. 44% and 23 vs. 38%
      (placebo vs. prednisolone). Fifteen patients (7.5%) lost HBsAg. Three out of 22
      cirrhotic patients (14%), one of whom received prednisolone pre-treatment,
      developed hepatic decompensation with a fatal outcome. Prednisolone pre
      treatment, enhances the effect of lymphoblastoid interferon in chronic hepatitis
      B. Interferon treatment (with and without prednisolone) should be used with
      caution in patients with cirrhosis and avoided in patients with evidence of
      hepatic decompensation.

PMID- 9771061
TI  - [A young woman with metabolic acidosis and recently discovered IDDM without
      ketonuria. A rare autoimmune (?) combination of hypothyroidism, diabetes mellitus
      and distal renal tubular acidosis].
AB  - A case of a 29-year-old woman with a multiple autoimmune disorder is reported.
      She had a history of hypothyroidism since the age of 18. She was admitted to
      hospital due to hyperglycaemia. At admission she had hyperglycaemia, metabolic
      acidosis, but no urinary ketone bodies. Further laboratory studies revealed that
      the acidosis was due to distal renal tubular acidosis rather than diabetic
      ketoacidosis (although the patient had type 1 diabetes mellitus). Blood tests
      revealed antibodies to glutamic acid decarboxylase (GAD-65; associated with type
      1 diabetes mellitus), thyroid and adrenal tissue, and gastric parietal cells. The
      patient had not developed pernicious anaemia or Addison's disease. The multiple
      positive antibody titres in this patient indicate that the diabetes,
      hypothyroidism and distal renal tubular acidosis are part of an autoimmune
      syndrome.

PMID- 9771063
TI  - [Vitamin B12 uptake: a new insight into molecular mechanisms].

PMID- 9771062
TI  - [Interaction between paroxetine and clomipramine as a possible reason for
      admission to a department of internal medicine].
AB  - A 79-year-old woman was admitted due to increasing dizziness during the past six
      days. She had been treated with clomipramine 75 mg daily for years, and in
      addition had received paroxetine 20 mg daily for the last eight days. Both drugs
      were terminated and the symptoms disappeared. Thirty-six hours after taking the
      last drugs, the S-clomipramine plus S-desmethylclomipramine were 790 mmol/l. The
      symptoms were probably related to this high serum level caused by interaction
      with paroxetine.

PMID- 9771064
TI  - [Picture of the month. Relapsing polychondritis of the ear].

PMID- 9771065
TI  - ["Prime-MD"--a rapid method for diagnosis of mental disease in general practice].

PMID- 9771066
TI  - [Thrombosis prophylaxis after cerebrovascular attack].

PMID- 9771067
TI  - [Doppler measurement in patients with latent forefoot ischemia].

PMID- 9771068
TI  - [Paradigmatic shift in the treatment of epilepsy?].

PMID- 9771069
TI  - [Guidelines on antiepileptic treatment of children].

PMID- 9771070
TI  - [Alcohol abuse treatment is more than Antabus].

PMID- 9771071
TI  - [Drink milk and become more stupid].

PMID- 9771072
TI  - [A protest and two proposals].

PMID- 9771073
TI  - [Titles are power--the professors do not wish to discuss statins].

PMID- 9771074
TI  - [Crisis intervention/debriefing--flop or fact?].

PMID- 9771075
TI  - [Clinical and histopathological examination of enucleated eyes with contusion
      ruptures of cornea after radial keratotomy].
AB  - Histopathological (histological, histochemical, and morphometric) examinations of
      8 enucleated eyes with contusion ruptures of the cornea 2-13 years after radial
      keratotomy showed two patterns of changes caused by contusion and peculiar
      reparative processes in the keratotomic incisions. A characteristic feature of
      contusion injury after radial keratotomy is combination of changes typical of
      contusion and an extensive perforating corneal wound after its rupture along the
      incisions. Reparative processes in the keratotomic incisions were regarded as
      incomplete cicatrization resultant from inhibition of keratoblastic activity
      after a low-traumatic operation. The structure of cicatrice after keratotomic
      incisions differed from that of corneal cicatrices after cut wounds. The
      cicatrice consisted of an epithelial plug and stromal par with picrinophilic
      amorphous filamentous material and individual keratocytes but no proteoglycanes
      or filamentous matrix. The length of cicatrice was 80-95% of intact cornea
      thickness. The structure of keratotomic cicatrice implies its insecurity and
      sensitivity to blunt injury, and therefore patients should be informed of the
      necessity to avoid injuries.

PMID- 9771076
TI  - [Combination of phacoemulsification and implantation of soft intraocular lens: a
      most important new trend in surgery for cataract (first clinical experience)].
AB  - Sixty-seven patients with cataracts of different degree of maturity were operated
      on using phacoemulsification with implantation of soft IOLs through a dot self
      hermetized incision. The advantages of this method over interventions with a
      large incision are a shorter postoperative rehabilitation (2-3 weeks), no
      postoperative astigmatism, low traumatism, and a lower risk of pre- and
      postoperative complications. Insertion of soft IOLs with injectors permits
      intraocular correction of vision through a dot incision used in
      phacoemulsification; no sutures are needed, and hospital stay is decreased to
      just 1-2 days.

PMID- 9771077
TI  - [Results of solid monolithic intraocular lenses implantation made by
      photopolymerization].
AB  - Results of experimental and clinical trials of a new solid intraocular lens made
      by an original technology from an acrylic polymer oligocarbonate methacrylate are
      analyzed. This IOL is monolithic, the diameter of the optic part is large, and
      the centering openings are made on special influxes beyond the optic zone of the
      lens. Results of experimental trials on rabbits and clinical use of T-70C "J"
      IOLs are discussed. The authors emphasize a high stability of the lens in the eye
      and a low incidence of postoperative complications, which they explain by lack of
      toxicity of the material, design, and simple procedure of implantation of this
      IOL.

PMID- 9771078
TI  - [Restoration of retinal functional activity after surgical treatment of its
      detachment in patients with different eyeball injuries].
AB  - Nineteen case histories are analyzed: 1) 6 patients with postperforative
      detachment of the retina; 2) 8 patients with detachment of the retina after a
      penetrating wound with introduction of a foreign body; and 3) 6 patients with
      postcontusion detachment. The restoration of the alpha and beta ERG waves
      depended on the type of injury: after penetrating wounds, the changes in the
      retinal electrogenesis were the most manifest during the initial and early
      postoperative period; foreign bodies aggravated and decelerated the regeneration
      of visual function, contusion trauma of the eye is the most unfavorable factor
      complicating the restoration of visual functions; involvement of the paired
      (intact) eye is typical, as is changed functional reaction of the retina in
      injuries of all types.

PMID- 9771079
TI  - [Photorefractive keratectomy by excimer laser for correcting myopia and myopic
      astigmatism].
AB  - Photorefraction keratectomy (PRK) was carried out using Nidek EC-5000 eximer
      laser in patients with myopia of different degree and myopic astigmatism. After
      12 months, visual acuity without correction was 0.6-1.0 diopters in all patients
      with slight myopia, 0.7-1.0 in 95% of patients with medium myopia, and 0.8-1.0 in
      86% of patients with high myopia. A lower visual acuity in high myopia was caused
      by retinal complications of myopia. The results of refraction after PRK depended
      on the severity of myopia and patient's age. The degree of myopia regression
      depended on preoperative refraction and was more expressed in high myopia. Young
      patients developed a more expressed tendency to decrease of postoperative
      refraction. The results indicate that eximer laser is an effective and reliable
      tool for correcting myopia of different degree and myopic astigmatism.

PMID- 9771080
TI  - [Prospects of using latanoprost, prostaglandin F2 alpha analog, in hypotensive
      therapy for glaucoma].
AB  - Hypotensive efficacy and tolerance of a new antiglaucoma drug lathanoprost, a
      0.005% xalathane solution, prostaglandin F2 alpha analog, is studied. A single
      instillation of xalathane decreased ophthalmic tone in normal subjects and
      glaucoma patients with increased intraocular pressure. Combination of the drug
      with other hypotensive agents (pilocarpine + timolol) amplified their hypotensive
      effects. Long (3 months) follow-up showed that xalathane efficacy is comparable
      to that of pilocarpine and timolol combination but it is tolerated much better.

PMID- 9771081
TI  - [Xalathane: comparative assessment of efficacy and safety in hypotensive therapy
      of glaucoma].
AB  - Hypotensive efficacy and safety of local monotherapy with 0.005% xalathane (once
      a day) and combined therapy with 0.5% timolol (twice a day) and 2% pilocarpine (3
      times a day) are compared in 24 patients with primary open-angle glaucoma. Mean
      decrease of intraocular pressure was significant in both groups. No side effects
      of xalathane were recorded. In one case there was a slight reddening of the eye
      and a sensation of discomfort Pilocarpine therapy was associated with miosis in
      all patients; half of them complained of obscure vision and headache after
      instillation. Monotherapy with xalathane is safe sufficiently effective, and
      comparable to combined therapy with timolol and pilocarpine.

PMID- 9771082
TI  - [Results of fraxiparin and ticlid therapy of acute retinal vessels occlusion].
AB  - Out of 78 patients with occlusive processes in retinal vessels aged 22-78 years,
      28 were treated by combined therapy including heparin (group 1, controls) and for
      the rest 54 (test group) heparin was replaced by fraxiparin. Fraxiparin is a low
      molecular heparin administered parabulbarly in a dose of 0.07 ml with 0.03 ml
      isotonic sodium chloride. Forty-two out of 54 patients in the test group were
      administered ticlopedin (ticlide), a disaggregant, in a daily dose of 250 mg (1
      tablet) for 1 month; blood aggregation and lacrimal fluid coagulation and
      fibrinolytic activities were monitored over the course of treatment. Fraxiparin
      sooner improved visual acuity and caused a lesser number of side effects: in
      group 1 visual acuity improved in 45.8% and did not change or deteriorated in
      54.2%, whereas in the fraxiparin group these values were 68.58 and 31.42%,
      respectively. Ticlide decreased the risk of repeated occlusions, which occurred
      in 4 patients vs. 11 in the control group, including those presenting as
      myocardial infarctions and brain strokes.

PMID- 9771083
TI  - [Express diagnosis of eye adenovirus infection by fluorescent antibody method].
AB  - Adenoviruses often cause epidemic keratoconjunctivitis. The infection is highly
      contagious, often leads to corneal opacities, and is therefore to be timely
      diagnosed and properly treated. The authors propose a method for rapid diagnosis
      of adenovirus infection based on examination of a scraping off the conjunctiva by
      indirect immunofluorescence with polyvalent fluorescent rabbit serum and offer
      recommendations on the use of this method. Using this technique, adenovirus
      antigen was detected in 14 (61%) out of 23 patients with acute follicular
      conjunctivitis and in 19 (95%) out of 20 patients with keratoconjunctivitis.
      Despite clinical cure after antiviral therapy, the antigen persisted for 1 month
      in 22-30% patients and in some patients for 3 months (as a rule, it was in
      patients treated too late or ineffectively or after corticosteroids). That is why
      maintenance antivirus therapy is recommended for 2-3 months after clinical cure.

PMID- 9771084
TI  - [Prospects of immunotropic therapy of traumatic uveitis].
AB  - Traditional corticosteroid and antiinflammatory therapy should be supplemented
      with new immunocorrective drugs in patients with traumatic uveitis and ocular
      subatrophy. Immunotherapy is a pathogenetically justified and perspective trend
      in multiple-modality treatment of patients with injuries to the organ of vision.
      The authors validate the use of immunocorrectors utilized in general
      transplantology for preventing rejection crisis. Immunostimulants or
      immunosuppresants can be added to treatment protocols for patients with traumatic
      uveitis, depending on the changes in the patient's immune status. New
      immunotropic drugs affecting all components of immunity are needed.

PMID- 9771085
TI  - [Computer treatment of strabismus and amblyopia using random-dot stereograms].
AB  - Application interactive CLASS software for stimulating productive binocular
      cooperation based on random-dot patterns and stereograms was used for treating
      strabismus and amblyopia in 105 children during a standard course of treatment.
      The children were divided into 3 groups treated by the CLASS alone (1), Class +
      two other application programs (2), and CLASS + traditional methods. General
      positive changes (improvement of visual acuity, decrease of eye deviation, etc.)
      were similar in these 3 groups. Positive effect of CLASS exercises on binocular
      visual mechanisms was significant. Due to precise evaluation of binocular
      interaction provided by CLASS, positive changes in binocular cooperation and
      stereovision were attained in 93% of children.

PMID- 9771086
TI  - [Effect of local revascularization of choroid on ocular tissues and lipid
      peroxidation in experimental atherosclerotic chorioretinopathy].
AB  - Lipid composition and lipid peroxidation in ocular tissues were assessed in 42
      rabbits with hypercholesterolemia. The levels of nonesterified cholesterol,
      diacylglycerides, nonesterified fatty acids, and of malonic dialdehyde were
      increased and the content of endogenous antioxidants decreased in animals with
      experimental atherosclerotic chorioretinopathy. Surgery (local revascularization
      of the vascular coating with two flaps) resulted in improvement of ocular
      biochemistry and microcirculation in the posterior segments of the eye and in
      recovery of the functional intactness of the retina and choroid.

PMID- 9771087
TI  - [Angiogenesis in rabbit cornea after disruption of descemet's membrane in the
      presence of heparin].
AB  - Nd:YAG laser was used to disrupt Descemet's membrane in rabbits in order to
      provoke the hypothetical release of angiogenic activity without a significant
      traumatic inflammation. Corneal vascularization was elicited only with
      simultaneous administration of heparin, which alone was unable to initiate the
      growth of new blood vessels. It is probable that basic fibroblast growth factor
      (bFGF) was released from its depot in Descemet's membrane and its critical
      concentration was saved by heparin. The importance of Descemet's membrane is
      highlighted by the fact that a similar lesion of midstroma could not induce
      angiogenesis even if aided by heparin. However, some other mechanisms cannot be
      ruled out, as bFGF acts in paracrine and amacrine mode only.

PMID- 9771088
TI  - [Epidemiology of keratoconus in the Urals].
AB  - Analysis of the prevalence of keratocone in the Urals showed it to be 1:500,000
      population. Young capable men suffer from this condition 3 times more often than
      women, urban residents more often than rural ones (5 times more often). The
      prevalence of keratocone in the Urals is the maximal in the ecologically
      unfavorable Chelyabinsk district: 1:250,000.

PMID- 9771089
TI  - [Impairment of visual pathway function in right hemisphere in patients with
      arteriovenous malformation of the parietooccipital area of left hemisphere].
AB  - Marked arteriovenous malformation in the left parietooccipital area manifested
      only by symptoms of associative migraine involving changes of visual fields
      indicative of impaired functions of symmetrical compartments of the other brain
      hemisphere. Visual evoked potentials were changed in this patient because of
      dysfunction of both hemispheres and largely because of disorders in brain
      structures symmetrical to the site of arteriovenous malformation. This can be
      regarded as a manifestation of the so-called stealing phenomenon, when blood
      supply to one brain compartment is decreased because of excessive blood delivery
      to other regions of the brain. The results permit us to hypothesize regulation of
      blood supply to symmetrical compartments of brain hemispheres.

PMID- 9771090
TI  - [Alomide eyedrops in the treatment of allergic conjunctivitis and
      keratoconjunctivitis].
AB  - New drug lodoxamine (alomide) opens new vistas in the treatment of allergic
      diseases of the eyes highly prevalent both in adults and children. This drug
      prevents release of mast cell mediators and delays eosinophil migration to
      conjunctival and corneal tissue, thus exerting a spectrum of antiallergic
      effects. Clinical studies carried out in 170 patients demonstrated a high
      efficacy of alomide in the treatment of subacute and chronic pollenosis
      conjunctivitis, spring keratoconjunctivitis, multiple and toxic allergic
      keratitis, and other allergic conjunctivities. Alomide can be used as a
      preventive drug in patients with allergies under high-risk conditions and in
      patients wearing contact lenses. It is effective in combined therapy of keratitis
      and keratouveitis. Alomide eye drops are well tolerated.

PMID- 9771091
TI  - [Congenital cystic eye].
AB  - Three patients with congenital cystic eye are described. Clinical manifestations
      of the condition were absence of the eyeball with massive cystic lesions
      occupying the orbit and protrusion of eyelids. Contralateral eye may be involved.
      This abnormality can be associated with systemic developmental abnormalities.
      Histopathologically there was no ocular structure in the orbit. The cyst wall
      consisted of two layers. The outer layer consisted of fibrous connective tissue
      and the inner layer of neuroectodermal tissue with a high level of antibodies to
      neuronspecific enolase. The cyst contained light yellowish fluid similar to
      cerebrospinal fluid. Etiology, differential diagnosis. and treatment of the
      condition are discussed.

PMID- 9771092
TI  - [A rare case: removal of intraocular foreign body].

PMID- 9771093
TI  - [Pathogenesis and treatment of low (normal) pressure glaucoma].

PMID- 9771094
TI  - [Contrast and color sensitivity in the diagnosis of glaucoma: neurophysiological
      aspects].

PMID- 9771095
TI  - [Doppler ultrasonographic examination in glaucoma].

PMID- 9771097
TI  - [Personal identification by X-ray views of the chest cavity].
AB  - The topical and unsolved problems of recognizing somebody's identity of dead and
      alive persons are outlined. An original procedure and algorithm of identity by
      the chest structural features revealed by X-ray study are proposed. Mathematical
      criteria for assessing the found individual signs to prove somebody's identity
      have been developed. An analysis has been made of 29 cases with the proposed
      procedure when the employment of conventional criminological and forensic medical
      methods was impossible due to significant injuries of the head and extremities in
      the corpse.

PMID- 9771096
TI  - [The potentials of spiral computed tomography in the diagnosis of lesions of the
      extracranial carotid arteries].
AB  - The paper summarizes the results of examination of 30 individuals aged 27 to 66
      years who had extracranial carotid lesions by using computed tomographic
      angiography (CTA), computed tomography, Doppler ultrasonography, power Doppler
      imaging, digital subtraction angiography. A procedure for CTA and analysis of
      data and for determination of the degree of stenosis has been developed. The
      potentialities of CTA in visualization of extracranial carotid diseases are
      shown.

PMID- 9771098
TI  - [The X-ray characteristics of the status of the heart and vessels in patients
      with arterial hypertension exacerbated by a myocardial infarct].
AB  - This study assessed the diagnostic value of X-ray characteristics of the heart
      and pulmonary circulation in CHD patients with aggravated arterial hypertension
      in three age groups (22-40, 41-59, and 60 years or older). The study covered 246
      patients with acute myocardial infarction (140 hypertensives and 106
      normotensives) and 182 with postinfarct cardiosclerosis (88 patients with
      arterial hypertension and 94 without this condition). All the patients underwent
      teleradiography, 12-lead EGG, echocardiography, and coronary ventriculography.
      While comparing the two study groups, the X-ray criteria show deteriorated left
      and right cardiac functions and altered aorta due to both its atherosclerotic
      changes and lower left ventricular contractility.

PMID- 9771099
TI  - [The role of dynamic contrast magnetic resonance tomography in the complex
      radiation diagnosis of focal hepatic lesions].
AB  - The results of complex radiation study of 269 patients with various focal hepatic
      diseases were analyzed. Present day methods of radiation study were used. Dynamic
      contrast magnetic resonance imaging (DCMRI) was made in 62 patients. It is
      concluded that DCMRI is higher sensitive in detecting focal hepatic diseases than
      other techniques. The time course of changes in signal intensity in different
      abnormalities greatly differs in quantitative and qualitative parameters, which
      differentiates the nosological nature of the revealed changes to a high accuracy.

PMID- 9771100
TI  - [Interventional radiology in the treatment of primary and metastatic liver
      cancer].
AB  - The data available in the literature and the authors' own treatment outcomes in
      600 patients with primary and metastatic carcinoma of the liver (in 1983-1996)
      were analyzed. Systemic or intravascular therapy as regional drug infusion,
      embolization, chemoembolization of the hepatic artery (CEHA) and portal vein
      (CEPV) was performed in unresectable cases. Whether pre- and postoperative
      chemoembolization was evaluated in resectable tumors. It is concluded that X-ray
      endovascular interventions play an important role in the treatment of malignant
      hepatic tumors. Transcatheter CEHA alone and in combination with CEPV is the most
      effective current treatments of unresectable carcinoma of the liver. In some
      patients, preoperative CEHA makes it possible to remove the tumor previously
      considered to be unresectable. Resection in combination with adjuvant CEHA and
      CEPV reduces the incidence of postoperative recurrences. The combined approach to
      treating malignant hepatic neoplasms expands the possibilities of delivering care
      to patients and improving late outcomes.

PMID- 9771101
TI  - [The internal structure of soft and bony tissues studied by X-ray refraction
      introscopy].
AB  - Whether X-ray refractional introscopy can be used to examine biological objects
      was studied. The characteristic emission of an X-ray tube provided refractional
      radiograms of the rat heart and limb, which allow one to make out the details of
      the structure of soft tissues and bones invisible on absorption radiograms under
      the same conditions. High-contrast refractional images of calcified formations
      were seen in the real-time mode when they were registered with a two-coordinate
      TV detector. The potentialities of the new method and medical diagnostic means
      are discussed.

PMID- 9771102
TI  - [Computed tomography in metastatic lung lesions (a review of the literature and
      the author's own data). I. Pathogenesis and the CT semeiotics].

PMID- 9771103
TI  - [Computed tomography in metastatic lung lesions (a review of the literature and
      the author's own data). II. Detection and differential diagnosis].

PMID- 9771104
TI  - [The University of X-ray Laboratory Assistants. Lesson 4. Megabyte memories].

PMID- 9771105
TI  - [The history of the development of roentgenology in the Republic of Tatarstan].

PMID- 9771106
TI  - [The present-day outstanding surgeon].

PMID- 9771107
TI  - [Surgery Research Center, Russian Academy of Medical Sciences: advanced post of
      Russian reconstructive surgery (on occasion of 35th anniversary)].

PMID- 9771108
TI  - [Role of academic B.V. Petrovskii in the development of extracorporeal
      circulation].
AB  - The paper shows the role of Academician B.V. Petrovsky and his scientific school
      in the development of extracorporeal circulation, as well as his ties with S.S.
      Bryukhonenko (1890-1960), the founder of extracorporeal circulation in Russia.
      Heart-lung apparatuses were designed with the participation of collaborators of
      the Surgery Research Center (SRC), Russian Academy of Medical Sciences. A short
      account is given of the principal aspects of extracorporeal circulation, which
      have been studied at the SRC, such as protective blood flow distribution,
      centralization of circulation, the optimal perfusion rate, criteria for adequate
      extracorporeal circulation, control of blood coagulation and acid-base state,
      blood concentration, extracorporeal circulation with autooxygenation, hyperbaric
      perfusion, normothermal perfusion with continuous warm blood cardioplegia).

PMID- 9771109
TI  - [Intraoperative angioscopy in vascular reconstructive surgery].
AB  - Based on the data available in the literature and their own findings, the authors
      analyzed the value of angioscopy in the reparative surgery of low limb vessels.
      Some cases of clinical application of intraoperative angioscopy are described and
      guidelines for the use of angioscopy as an intraoperative control of the quality
      of reparative surgery on low limb vessels.

PMID- 9771110
TI  - [Use of total myorelaxation for placing a laryngeal mask and further artificial
      lung ventilation].
AB  - The specific features of placing a laryngeal mask (LM) under total myoplegia were
      studied. The first attempt at placing LM was successful in 98.7% of cases. A
      pressor response to LM appeared as increases in heart rate by 5.6% with combined
      intravenous ketamine anesthesia used during laparoscopic cholecystectomies (Group
      1), by 10.2% at saphenectomies (Group 2), and by 6.7% with barbiturates. When
      diprivan was used, changes were absent in Group 1, there were increases in mean
      blood pressure and heart rate by 10 and 6.6%, respectively, in Group 2. The
      response to tracheal intubation was significant under all types of anesthesia.
      Regurgitation and aspiration were absent in all groups. The use of total
      myoplegia to place LM allows different current anesthetics to be used in the
      optimal doses and the procedure for placing LM to be greatly simplified.

PMID- 9771111
TI  - [Variations of cardiac cycle length in patients with coronary heart disease
      before and after aortic coronary bypass surgery].
AB  - It is well known that variations in cardiac cycle length or heart rates may be
      used for noninvasive evaluation of autonomic cardiovascular control. The
      investigation uses an original procedure. The data for analysis of cardiac cycle
      length variations (CCLV) are those obtained regularly at follow-up intervals,
      random 24-hour Holter 2-lead ECG recordings for 5 sec, and simultaneously
      calculated continuous sequence of mean heart rate. With the procedure, the
      correlations of CCLV with the parameters reflecting the early postoperative
      status of patients with CHD, including acute myocardial infarction, acute heart
      failure, rhythm and conduction disturbances, as well as age, operative stress,
      concurrent diseases. The findings are of both diagnostic and predictive value at
      subsequent stages of CHD treatment.

PMID- 9771112
TI  - [Cardiac rhythm and conduction disturbances during surgical correction of the
      patent atrioventricular canal].

PMID- 9771113
TI  - [Treatment of cicatricial esophageal strictures and esophageal anastomoses by
      using flexible endoscopes].
AB  - The paper presents the results of endoscopic treatment of benign esophageal
      strictures of various origin in 294 patients and of scar stenosis of esophageal
      anastomoses in 157 patients. The basic endoscopic techniques of expansion are
      balloon hydrodilatation by using catheters, 10-30 mm in diameter and bouginage of
      Savary's (maximum outside diameter 40 Fr) and Eder-Puestow's (with olives, 15-20
      mm in diameter) bougies. Good and excellent direct results were obtained in 57.1%
      of patients with esophageal strictures and in 87.8% of patients with stenoses of
      digestive anastomoses. Esophageal perforation occurred in 1.03% of patients with
      esophageal strictures. There were no serious complications after endoscopic
      treatment of postoperative stenoses. To prevent restenoses, endoscopic treatment
      should include regular outpatient maintaining dilatations by using dilatators at
      longer intervals during 3-6 months.

PMID- 9771114
TI  - [Treatment and prevention of cicatricial strictures and fistulas of biliary
      ducts].
AB  - The paper summarizes the experience gained by the Department for Surgery of the
      Liver, Biliary Ducts, and Pancreas, Surgery Research Center, in treating patients
      with corrosive strictures and fistulas of the biliary ducts since 1967. It
      considers the causes of this abnormality, the nature of corrective operations on
      the great biliary ducts, complications due to the type of a surgical
      intervention. Analyzing the reasons for poor postoperative outcomes provides the
      optimal time of carcass drainages, the optimal diameter of the biliodigestive
      anastomosis made to have good results. Emphasis is laid on the specific features
      of biliary surgery if there are profound inflammatory and infiltrative or scarry
      and commissural changes in the hepatoduodenal ligament to prevent possible damage
      to the great biliary ducts.

PMID- 9771115
TI  - [Blood supply of wrist and forearm after exclusion of radial vascular fascicle of
      all length from blood stream].
AB  - The arm and forearm are commonly used in plastic and reconstructive surgery as a
      donor site for harvesting free microsurgical revascularized autografts, which
      include not only soft tissues, but when necessary, a fragment of radial bone as
      well. The radial autograft is taken together with radial vascular bundle, the
      radial artery is so being excluded from participation in hand and forearm blood
      flow. Until now there are no common opinion of expedient reconstruction of the
      radial artery because there are no evidence of visible blood flow disturbances in
      the hand. There are no convincing data on the functional status of the hand in
      long-term postoperative period and on the ways and degree of compensation of
      circulation. It is very important that evaluation of the ways and degree of blood
      flow compensation may play a great part in the problem of hand replantation, that
      is to determine the influence of the extent of blood flow restoration not only on
      hand viability, but on the long-term functional outcome as well. This
      investigation has revealed impaired blood supply and metabolism in hand soft
      tissues and bones by using the forearm as a donor site for taking free
      microsurgical revascularized autografts by radionuclide and ultrasound methods.

PMID- 9771116
TI  - [Estimation of vascular blood flow velocity in the breast neoplasms].
AB  - Based on examinations of 133 females having the normal breast, benign and
      malignant tumors, the potentialities of color Doppler mapping of breast vessels
      are shown. Cancers showed an increased vascularity in the peritumor areas and
      high flow velocity (Vmax' Vmean) in the surrounding tumor vessels. These criteria
      are not related to the size of a malignant tumor.

PMID- 9771117
TI  - [Orthotopic liver transplantation].
AB  - Orthotopic liver transplantation is the only method of choice for many severe
      liver diseases with poor prognosis. The development of liver transplantation
      programmes is based on medical science achievements and high technology in
      surgery, anesthesiology and perfusiology. The experience of the Surgery Research
      Center, Russian Academy of Medical Sciences, made it possible to obtain positive
      results of liver transplantation and posttransplantation management. This in turn
      provided longer survival for 80% of recipients. At the same time the mortality of
      potential recipients was 60.4%, which is due to the greater shortage of donor
      organs and which is the main problem in the development of organ grafting in
      Russia. The fact that there is a high proportion of children who are recipients
      for the donor's liver requires that liver transplantation from living related
      donors should be developed.

PMID- 9771118
TI  - [Pyogenic infectious complications in recipients with allogenic kidneys: clinical
      and bacteriological aspects].
AB  - The bacteriological study of wound discharge indicated no changes in the
      structure of the microflora in the allogenic kidneys of recipients throughout the
      follow-up. Among microbes isolated there were prevalent gram-positive microbes
      whose proportion has slightly increased in the past year, with Staphylococcus,
      mainly epidermal Staphylococcus, which contributes to the etiology. At the same
      time, studies of wound discharge in the past years showed that the incidence of
      mixed infections had increased from 4.3 in 1989-1991 to 15.6% in 1994-1997.
      Bacteriological urinalysis found no great differences in the etiological
      structures of the microflora. Gram-negative microbes are prevalent in all
      patients in three periods of follow-up. Noteworthy, there was an increase in the
      amount of yeast fungi (from 5.7 to 21.1%). Urinalysis showed that the rates in
      the isolation of bacterial and bacterial and fungal associations were steady
      state and higher in all patients (20, 4-23, 5%). Examining the etiological
      structure of the pathogens of sepsis ascertained that patients of the early
      observation were found to isolate gram-negative microorganisms more frequently,
      while those of other observation periods have gram-positive ones. The overall
      proportion of microbial and microbe-fungal associations was 10.3% in the past 9
      years. Since the patient's body is occupied by other pathogens due to
      immunosuppression, sepsis or wound infection was accompanied by high bacteriuria,
      cytomegalovirus infection, pneumocystic pneumonia, fungal infection, etc. For
      this reason, the patients had actually much higher quantities of mixed infections
      in sepsis, wound infection, or urinary infection than those taken into account
      while studying the only type of an infectious complication. The above leads to
      the conclusion that the incidence of mixed infection of recipients of allogenic
      kidneys is rather high. This infection substantially makes the choice of drugs
      and therapy difficult, the course of a wound process aggravated. For successful
      control of mixed infections, it is necessary to introduce new drugs having a high
      activity against bacteria, fungi, viruses, and protozoa and to use the latest
      differentially diagnostic culture media, to make diagnosis and treatment of
      pyoseptic diseases better.

PMID- 9771119
TI  - [Organization of postgraduate training of physicians and nurses at the Surgery
      Research Center, Russian Academy of Medical Sciences].

PMID- 9771121
TI  - [The pathologic system].
AB  - The pathological system (PS) is a new pathological integration originating from
      the primary and secondary altered CNS structure, whose activity has a dysadaptive
      or direct pathogenic significance for the body. An important role in the
      formation of PS is played by hyperactive CNS structure which acquires the role of
      a pathological determinant. Disturbances in the inhibitory mechanisms of CNS
      structures involved in the PS and enhanced excitability of their neurons promote
      the formation of PS. Negative feedbacks in PS are ineffective due to the
      competence of inhibitory mechanisms in the determinant and other parts of the
      system. Owing to their permanent activation, positive intrasystemic feedbacks are
      stabilized by plasticity processes. All these changes promote the stabilization
      of PS and the increase of its resistance to endogenous corrective influences. The
      major pathogenetic significance of PS is that it is a pathophysiological basis of
      the respective syndrome. Every neuropathological syndrome has PS of its own. By
      creating a generator in the definite, pathogenetically significant structure of
      CNS, one can convert this structure into the pathological determinant, which
      induces the appropriate PS and thus causes the respective neuropathological
      syndrome. Hyperactive PSs suppress the physiological systems by causing
      disturbances in CNS activity.

PMID- 9771122
TI  - [Mechanisms of resistance to emotional stress: advantages of individual
      approach].
AB  - cal concern for widespread averaged approach to studying various stress indices
      is presented. The author demonstrates that the subjects predisposed and resistant
      to different physiological dysfunctions and survival are revealed in a great
      variety of experimental models and experiments. The animals resistant and
      predisposed to emotional stress are shown to present different behavior,
      autonomic reactions, varying rates of c-fos gene expression in the brain,
      different levels of catecholamines and oligopeptides in the brain structures.
      Specific chemical integration of neurons in the limbic-reticular brain structures
      determines animal resistance to emotional stress.

PMID- 9771123
TI  - [Psychogenic stress: theory, experiment, practice].
AB  - Experiments on animals (rodents, beasts, primates) and observation in man have
      ascertained that psychogenic stress is the most important defensive state of
      living organisms, which is constantly involved in order to maintain their
      interaction with external psychogenic factors. Three types of stress should be
      distinguished, these include normostress, hypostress, and hyperstress.
      Normostress has definite limits within which optimal responses, which are typical
      for an individual are realized. Hyperstress develops as a defensive response to
      extremely strong (extraordinary) stimuli. Hypostress can be observed in the
      retarded development of self-regulation mechanisms. All three types of stress are
      provided by a fundamental property of living organisms--the self-regulation
      mechanism, which realizes the keeping back of normostress constancy, or return of
      hyper- and hypostress to the normostress status. And only if an extreme deficit
      of self-regulation mechanisms takes place, hyper(hypo)stress could become a
      condition for the development of pathology.

PMID- 9771124
TI  - [Changes in the ultrastructure of interneuronal connections in experimental
      chronic morphine poisoning].
AB  - To understand the mechanisms of brain activity and behaviour alterations in
      chronic morphine intoxication, it is especially important to analyze the changes
      occurring in the interneuronal connections. Analyzing cerebral cortical synapses
      during morphine treatment revealed that some new synapses formed. The newly
      formed synapses increased the total number of synapses of the cerebral cortex and
      reorganized synaptic architectonics. The changes in the synaptic architectonics
      accompanied ultrastructural changes of dendrites. The development of new synapses
      and changes of dendrites are the basis for the formation of pathological cerebral
      cortical systems.

PMID- 9771125
TI  - [Functional role and pharmacological regulation of the dopaminergic system of the
      brain].
AB  - The dopaminergic systems of the brain are thought to play a major role in the
      regulation of motor, cognitive, neuroendocrine functions and in the pathogenesis
      of several pathological conditions, including neurodegenerative diseases,
      affective disorders, schizophrenia, drug addiction, etc. Functional, biochemical,
      and pharmacological heterogeneity of dopamine receptors, which were divided into
      D1-like (D1 and D5 subtypes) and D2-like (D2, D3, and D4) families of receptors,
      has been postulated. The paper concerns the recent advances in the study of the
      structure and function of two main dopaminergic brain systems, i.e. nigrostriatal
      and mesolimbic. The problem of autoreceptor regulation of dopaminergic
      neurotransmission, particularly the processes of dopamine synthesis, release, and
      metabolism is discussed. The involvement of D2 and D3 dopamine autoreceptors in
      the control of these processes and differences in the mode of action of typical
      neuroleptics are analyzed. It is hypothesized that dopamine D3 autoreceptor is
      preferentially involved in the regulation of dopamine release while D2 one is
      responsible for the control of dopamine synthesis and metabolism in rat basal
      ganglia in vivo.

PMID- 9771126
TI  - [Plastic remodeling of the synaptic apparatus of skeletal muscles under
      physiological and pathological conditions].
AB  - The synaptic apparatus of skeletal muscles undergoes continuous remodelling, by
      adapting to the functioning level of the peripheral neuromuscular apparatus under
      normal conditions, compensating and restoring its impaired function in pathology.
      This reorganization has specific features depending on the factors that influence
      it, such as increased function, decreased or no function, neuronal and nerve
      damage, synaptic toxin intoxication, autoantibody action, disturbances of trophic
      influences, etc. Damage to any link of the neuromuscular apparatus due to the
      above factors is likely to be an essential condition for remodelling.

PMID- 9771127
TI  - [Induction of long-term depression (with anxiety and fear components) by
      immunization of rats against pargyline].
AB  - The active immunization of albino rats against pargyline (a MAO B inhibitor)
      induced the formation of antibody to pargyline and results in deep depressive
      changes and fear. These changes were observed within 6 weeks after the first
      immunization. Therefore, it opens the possibility to model depression long by
      exerting the minimum influences. There was also a long-term modulation of craving
      for alcohol.

PMID- 9771128
TI  - [A neurophysiological model of the "paroxysmal brain" (cerebral mechanisms in the
      genesis of paroxysmal states)].
AB  - This paper attempts to elucidate whether common (nonspecific) brain mechanisms
      are responsible for seizures of epileptic and nonepileptic origin. A comparative
      study of the following 4 paroxysmal disorders--partial epileptic seizures,
      paroxysmal dystonia, pseudoseizures and panic attacks was performed. Spontaneous
      (EEG-mapping) and evoked (contingent negative variation-CNV) bioelectrical
      activity was measures in all patients several times during interictal periods and
      after 24-hour sleep deprivation. The main common neurophysiological features of
      these types of paroxysmal disorders were the increased total power of spontaneous
      electrical activity, an asymmetric increase of theta-EEC power in the right
      hemisphere, an increase in total amplitude of CNV. Readiness of the brain for the
      development of the paroxysms was characterized by dynamic increases of the above
      parameters of spontaneous and evoked bioelectrical activity.

PMID- 9771129
TI  - [Involvement of urokinase and its receptor in the remodeling of normal and
      pathological tissue].
AB  - Urokinase is the main component of the fibrinolytic system and comprises two
      functions. Namely, the catalytic domain enables to trigger the proteolytic
      cascade in blood and in the vessel wall, stimulating the activation of growth
      factors, matrix remodelling and smooth muscle cell proliferation. On the other
      hand, the amino terminal domain of urokinase that is homologous to epidermal
      growth factor promotes urokinase to bind to the specific receptor. The cell
      surface binding of uPA may initiate the activation of the second messengers,
      protein phosphorylation and cell migration. This dual function of urokinase
      affects vascular growth, as well as the intimal thickening of the vessel wall
      after intravascular injury. Also uPA and its receptor are implicated in many
      physiological and pathological processes, including ovulation, embryogenesis,
      cancer metastasis, inflammation, and wound healing.

PMID- 9771131
TI  - [Principles of biochemical diagnosis of early infection process].
AB  - The paper outlines major achievements of biochemical diagnosis of a wound
      infectious process. Various classifications of its methods are given. The most
      promising approaches to predictive diagnosis of wound suppuration, pyoresorptive
      fever and sepsis are discussed.

PMID- 9771130
TI  - [Mechanisms of neuronal calcium homeostasis destabilization caused by
      hyperstimulation of glutamate receptors].
AB  - The present paper summarizes the data obtained in studying the mechanisms of
      glutamate-induced deterioration of neuronal Ca2+ homeostasis. In the cultured
      mammalian central neurons, a short-term (< 1 min) glutamate (GLU, 100 mu)
      challenge is known to induce a readily reversible (transient) neuronal [Ca2+]i
      increase. In contrast, a long-term (15-30 min) GLU exposure leads to the
      appearance of high [Ca2+]i plateau or to the partial recovery of the increased
      [Ca2+]i. Experiments show that impaired [Ca2+]i recovery in the postglutamate
      period cannot be explained by the increased [Ca2+]i permeability of the neuronal
      membrane, as earlier considered. Moreover, a sustained elevation of [Ca2+]i
      during and after chronic GLU application is associated with a progressive
      decrease in Ca2+ permeability. The major cause of GLU-induced Ca2+ overload is
      the mitochondrial depolarization resulted from excessive Ca2+ influx into the
      mitochondria, the generation of free radicals and the opening of a "giant pore"
      in the inner mitochondrial membrane. This in turn suppresses both ATP synthesis
      and Ca2+ electrophoretic uptake into the mitochondrial matrix. In combination
      with [Ca2+]i-dependent acidification, this leads to the suppression of Ca2+
      release from the cell via Na+/Ca2+ exchanger and Ca2+/H+ pump of the neuronal
      membrane. Therefore, [Ca2+]i recovery following a long-term GLU treatment becomes
      strongly or even irreversibly compromised.

PMID- 9771133
TI  - [Central Institute of Tuberculosis].

PMID- 9771135
TI  - [The rehabilitation of patients with diabetic neuropathy of the oculomotor
      nerve].

PMID- 9771134
TI  - [The use of white and yellow turpentine baths with diabetic patients].
AB  - In patients with insulin-dependent diabetes mellitus while and yellow turpentine
      baths produced a positive effect on carbohydrate metabolism. White baths were
      more effective in respect to lipid metabolism, blood viscosity, produced a good
      effect on plasmic hemocoagulation factors. Both while and yellow turpentine baths
      were beneficial for capillary blood flow: initially high distal blood flow in
      patients with prevailing distal polyneuropathy decreased while in patients with
      macroangiopathy initially subnormal blood flow increased. Both white and yellow
      turpentine baths promoted better pulse blood filling of the lower limbs and
      weaker peripheral resistance of large vessels. In patients with non-insulin
      dependent diabetes mellitus white and yellow turpentine baths contributed to
      normalization of carbohydrate metabolism. Yellow baths were more effective in
      lowering lipids. White baths induced inhibition of platelet aggregation but had
      no effect on coagulation, yellow baths promoted a reduction of fibrinogen but had
      no effect on platelet aggregation. Yellow baths produced more pronounced effect
      than white ones on blood viscosity and microcirculation. Both yellow and white
      baths stimulated pulse blood filling, corrected peripheral resistance of large
      and small vessels of the lower limbs.

PMID- 9771136
TI  - [The potentials for the balneotherapy of obesity using arsenic-containing mineral
      water].
AB  - Arsenic mineral water from the Sinegorsk springs was tried in the treatment of
      experimental alimentary obesity in rat Wistar males and patients with exogenous
      constitutional obesity. Body mass, blood lipids, hepatic neutral lipids, glucose
      6-phosphate-dehydrogenase were measured. Arsenic mineral water proved able to
      reduce excessive body mass, correct blood lipid spectrum, normalize metabolic
      processes in the liver. Thus, arsenic mineral water can be used in balneotherapy
      of obesity.

PMID- 9771137
TI  - [The treatment of autoimmune thyroiditis using low-intensity laser radiation].

PMID- 9771138
TI  - [The staged rehabilitation of patients who have had a stroke].

PMID- 9771139
TI  - [The therapeutic action of kavinton electrophoresis in cerebrovascular diseases].

PMID- 9771140
TI  - [The modulating action of balneotherapy on the peroxidation processes in patients
      with ischemic heart disease].
AB  - The state of the system lipid peroxidation-antioxidant defense (LPO-AOD) was
      studied in 187 patients with ischemic heart disease on combined
      balneorehabilitation. The balneotherapy comprised effervescent magnesium-calcium
      and effervescent arsenic mineral water, artificial baths. Balneorehabilitation
      produced optimal results in high functional capacity of LPO-AOD system. In low
      functional activity of the system LPO-AOD balneological procedures may impair
      adaptive mechanisms and provoke balneoreactions. Combination of balneofactors
      with diet including polyunsaturated fatty acids enhanced antioxidant blood
      activity and modified LPO.

PMID- 9771142
TI  - [Interference currents in the treatment of patients with duodenal peptic ulcer].
AB  - 93 patients with duodenal ulcer were exposed to interference currents
      (transcerebral and epigastric exposure). These currents were found clinically and
      functionally effective. The improvement was also found in the trophic processes
      in the gastroduodenal area. Gastroduodenal mucosa contamination with Helicobacter
      pylori reduced.

PMID- 9771141
TI  - [The effect of contrast baths on the hemostatic function of patients with
      ischemic heart disease].
AB  - Contrast baths effects on hemostasis were studied in 72 patients with
      postinfarction cardiosclerosis and stable angina pectoris. Hemostasis was
      assessed by recalcification time, blood plasma tolerance to heparin, fibrinolytic
      activity, functional activity of antithrombin, soluble fibrin-monomeric complex,
      platelet count and aggregation. The results were compared to those in patients
      exposed to laser irradiation. Hydrotherapy with contrast baths was hemostatically
      effective in 70.9% of patients. Blood coagulation and platelet aggregation
      improved, the risk of intravascular microthrombogenesis diminished. Contrast
      baths had more pronounced beneficial effects on coagulation in ischemic heart
      disease of NYHA functional class II.

PMID- 9771144
TI  - [The effect of low-intensity physical therapeutic factors on the microsomal
      oxidative systems of the liver in an experiment].
AB  - The authors' rat experiments have shown that inhibition of pro-oxidant reactions
      in hepatocyte microsomal fraction in response to hepatic exposure to low
      intensive IR-laser radiation and low-intensity ultrasound combines with
      multidirectional action of these factors on the basic enzymes of the other
      oxidant system of hepatocyte microsomes--cytochrome P-450-dependent monooxigenase
      system.

PMID- 9771143
TI  - [Nonspecific resistance in patients with chronic gastritis undergoing treatment
      by drinking a calcium-sodium chloride low-mineralized mineral water].

PMID- 9771146
TI  - [The potable mineral waters of the Chuvash Republic].

PMID- 9771145
TI  - [Changes in the mineral metabolic indices of osteoarthrosis patients with the use
      of radon therapy and mud therapy].
AB  - As shown by investigations of alkaline phosphatase, plasma levels of calcium, non
      organic phosphorus, coefficient Ca/P in 58 patients with osteoarthrosis deformans
      before and after radon baths, mud applications or their combination, the highest
      biochemical effect was achieved in a group of patients on mud therapy.

PMID- 9771147
TI  - [The outlook for the use of the natural therapeutic resources of northern Tomsk
      Province for the rehabilitation of children and women (the Children of the North
      Federal Targetted Program)].

PMID- 9771148
TI  - [Physical methods of treating poliomyelitis patients].

PMID- 9771149
TI  - [The effect of physical factors on the action of other therapeutic means (the
      problem of therapeutic interference)].

PMID- 9771150
TI  - [The history of the Central Research Institute of Health Resort Medicine and
      Physiotherapy].

PMID- 9771151
TI  - Ischemic heart disease and stroke mortality in African-American, Hispanic, and
      non-Hispanic white men and women, 1985 to 1991.
AB  - We compare recent trends in ischemic heart disease (IHD) and stroke mortality in
      California among the 6 major sex-racial or -ethnic groups. Rates of age-specific
      and -adjusted mortality were calculated for persons aged 35 and older during the
      years 1985 to 1991. Log-linear regression modeling was performed to estimate the
      average annual percentage change in mortality. During 1985 through 1991, the
      mortality for IHD and stroke was generally highest for African Americans,
      intermediate for non-Hispanic whites, and lowest for Hispanics. Age-adjusted
      mortality for IHD declined significantly in all sex-racial or -ethnic groups
      except African-American women, and stroke rates declined significantly in all
      groups except African-American and Hispanic men. African Americans had excess IHD
      mortality relative to non-Hispanic whites until late in life, after which
      mortality of non-Hispanic whites was higher. Similarly, African Americans and
      Hispanics had excess stroke mortality relative to non-Hispanic whites early in
      life, whereas stroke mortality in non-Hispanic whites was higher at older ages.
      The lower IHD and stroke mortality among Hispanics was paradoxical, given the
      generally adverse risk profile and socioeconomic status observed among Hispanics.
      An alarmingly high prevalence of self-reported cardiovascular disease risk
      factors in 1994 to 1996, particularly hypertension, leisure-time sedentary
      lifestyle, and obesity, is a serious public health concern, with implications for
      future trends in cardiovascular disease mortality. Of particular concern was the
      growing disparities in stroke and IHD mortality among younger-aged African
      Americans relative to Hispanics and non-Hispanic whites.

PMID- 9771152
TI  - Failure of physician documentation of sleep complaints in hospitalized patients.
AB  - Sleep disorders are acknowledged to be common but remain underrecognized by the
      medical community, often attributed to the failure to question patients about
      their sleep quality. We examined the prevalence of sleep complaints (insomnia or
      excessive daytime sleepiness) in a group of general medical patients by
      administering a questionnaire to hospitalized patients in a Veterans Affairs
      tertiary care medical center. A total of 222 consecutive adults (215 men, 60 +/-
      14 years; body mass index, 24.8 +/- 5.6) completed the questionnaire. Of these,
      105 patients (47%) had either insomnia, excessive daytime somnolence, or both; 63
      (28%) had excessive daytime somnolence, which was severe in 27 (12%). Of 75
      patients (34%) who had insomnia, a third were taking hypnotic medication. Forty
      patients (18%) had snoring, which was associated with excessive daytime
      somnolence in 36, whereas 46 patients (21%) had either restless legs or a
      combination of leg jerks and leg kicking or twitching during sleep, associated
      with a sleep complaint (insomnia in 32). The medical records were subsequently
      reviewed to assess the admitting physicians' recognition of these symptoms. No
      record included mention of any patient symptom related to sleep. We conclude that
      symptoms related to sleep, some of which may be clinically important, are common,
      and that none of these complaints appear to be recognized by the physicians of
      record.

PMID- 9771153
TI  - Effect of mammography outreach in women veterans.
AB  - We undertook this study to test whether progressive intervention would increase
      the use of mammography. In 1995, we randomly assigned into 2 groups 717
      underserved women veterans in the Veterans Affairs Palo Alto (California) Health
      Care System (VAPAHCS) who earned less than $22,000 a year. The women were sent an
      informational letter and brochure explaining why mammography is needed and how
      often. The letter further requested that if the woman was due for a screening
      mammogram or if a lump or other recent change in her breast had occurred, that
      she call for scheduling of a free mammogram and a visit to the breast clinic.
      Women in group I (n = 351) received no further intervention. Women in group II (n
      = 366) received a follow-up phone call by a breast care nurse if they had not
      responded within 45 days of the informational mailing. The nurse talked to each
      woman about her particular needs, explained to her that the screening mammogram
      would be provided free of charge, and discussed transportation arrangements to
      the mammography facility. A total of 17 women in group I had mammograms versus
      100 in group II during the same time period. We conclude that the additional
      intervention of a phone call by a breast care nurse increased use by more than 5
      fold, which reached significance (P < .01).

PMID- 9771155
TI  - Are critically ill older patients treated differently than similarly ill younger
      patients?
AB  - Our goal was to determine whether critically ill older patients are treated
      differently than middle-aged patients. If so, what factors besides age contribute
      to that difference? Internal medicine residents (n = 46) and practicing
      internists (n = 41) received 8 clinical vignettes of 4 critically ill 85-year-old
      patients and 4 critically ill 50-year-old patients. Each patient had a distinct
      premorbid mental and physical state. Each respondent selected from 4 levels of
      therapeutic aggressiveness for each patient. The main outcome measure was the
      proportion of physicians who intended to treat the older of each matched pair of
      patients less aggressively than the younger one (that is, downgraded for age).
      Eight physicians (9%) treated a previously unimpaired 85-year-old patient less
      aggressively than a comparable 50-year-old patient. When the matched patients
      were either premorbidly mentally or physically impaired (but not both), about 20%
      of physicians downgraded for age. Most downgraded for age in matched patients who
      were premorbidly both mentally and physically impaired. We conclude that age
      alone does not engender much therapeutic bias against older patients as long as
      they are physically and mentally intact before the onset of their acute illness.
      As premorbid disabilities multiply, older patients may be treated less
      aggressively than younger ones with similar impairments and clinical
      presentations.

PMID- 9771156
TI  - Informing patients about the PSA test: a new requirement.

PMID- 9771154
TI  - Use of and interest in alternative therapies among adult primary care clinicians
      and adult members in a large health maintenance organization.
AB  - During spring 1996, random samples of adult primary care physicians, obstetrics
      gynecology physicians and nurse practitioners, and adult members of a large
      northern California group practice model health maintenance organization (HMO)
      were surveyed by mail to assess the use of alternative therapies and the extent
      of interest in having them incorporated into HMO-delivered care. Sixty-one
      percent (n = 624) of adult primary care physicians, 70% (n = 157) of obstetrics
      gynecology clinicians, and 50% (2 surveys, n = 1,507 and n = 17,735) of adult HMO
      members responded. During the previous 12 months, 25% of adults reported using
      and nearly 90% of adult primary care physicians and obstetrics-gynecology
      clinicians reported recommending at least 1 alternative therapy, primarily for
      pain management. Chiropractic, acupuncture, massage, and behavioral medicine
      techniques such as meditation and relaxation training were most often cited.
      Obstetrics-gynecology clinicians used herbal and homeopathic medicines more often
      than adult primary care physicians, primarily for menopause and premenstrual
      syndrome. Two thirds of adult primary care physicians and three fourths of
      obstetrics-gynecology clinicians were at least moderately interested in using
      alternative therapies with patients, and nearly 70% of young and middle-aged
      adult and half of senior adult members were interested in having alternative
      therapies incorporated into their health care. Adult primary care physicians and
      members were more interested in having the HMO cover manipulative and behavioral
      medicine therapies than homeopathic or herbal medicines.

PMID- 9771157
TI  - The urethral sling and stress urinary incontinence.

PMID- 9771158
TI  - Peyronie's disease: a difficult sexual dysfunction problem.

PMID- 9771159
TI  - Unusual vaginal laceration due to a high-pressure water jet.

PMID- 9771160
TI  - Mastoiditis, lymphoma, and AIDS.

PMID- 9771161
TI  - The benefits and challenges of an electronic medical record: much more than a
      "word-processed" patient chart.
AB  - The electronic medical record (EMR) will constitute the core of a computerized
      health care system in the near future. The electronic storage of clinical
      information will create the potential for computer-based tools to help clinicians
      significantly enhance the quality of medical care and increase the efficiency of
      medical practice. These tools may include reminder systems that identify patients
      who are due for preventative care interventions, alerting systems that detect
      contraindications among prescribed medications, and coding systems that
      facilitate the selection of correct billing codes for patient encounters.
      Numerous other "decision-support" tools have been developed and may soon
      facilitate the practice of clinical medicine. The potential of such tools will
      not be realized, however, if the EMR is just a set of textual documents stored in
      a computer, i.e. a "word-processed" patient chart. To support intelligent and
      useful tools, the EMR must have a systematic internal model of the information it
      contains and must support the efficient capture of clinical information in a
      manner consistent with this model. Although commercially available EMR systems
      that have such features are appearing, the builders and the buyers of EMR systems
      must continue to focus on the proper design of these systems if the benefits of
      computerization are to be fully realized.

PMID- 9771162
TI  - Two tests of instance-based and abstract rule-based accounts of invariant
      learning.
AB  - Two manipulations are argued to distinguish between instance-based and abstract
      rule-based accounts of invariant learning. Three experiments examined the effects
      of manipulating the type of invariant feature in the learning set, and the type
      of training schedules prior to test. In line with traditional research, selection
      bias at test was present when the invariant was the consistent inclusion of a
      stimulus item in the learning set. However, the degree of bias was identical when
      the invariant was the consistent exclusion of the stimulus item. In addition,
      negative transfer of training was observed when subjects were trained on one
      learning set and then shifted training to the opposite learning set, but no
      positive transfer of training was observed when subjects were trained on one
      learning set and then continued training using the same learning set. These
      results are argued to be evidence for instance-based accounts of invariant
      learning.

PMID- 9771163
TI  - Perceiving topological structure of 2-D patterns.
AB  - Four experiments investigated observers' sensitivity to the topological structure
      of visual stimuli. Three factors were taken to capture the topological structure
      of 2-D patterns: The number of disconnected components, the number of holes
      (connections), and inclusion relationships. If studied in isolation, any given
      topological property is typically confounded with the presence of particular
      features such as line terminations and contour length, or with Gestalt principles
      of perceptual organization. We went beyond existing studies and attempted to
      systematically remove potential confounds from the stimulus displays. Results
      showed that processing speeds for two-dimensional patterns are a function of
      their topological properties. The more patterns differ in their topological
      structure the easier they can be discriminated. Not only do all three topological
      factors contribute to pattern discriminability, they also can be combined to
      provide an overall measure of structural complexity. Forced choice comparison
      techniques agreed well with similarity judgments. Topological structure thus
      contributed to discriminability above and beyond many confounding variables.
      Claims suggesting a general topological analyzer in visual processing are
      discussed.

PMID- 9771164
TI  - Individual differences in the use of depth cues: implications for computer- and
      video-based tasks.
AB  - This paper reports an experimental study of individual differences in the
      performance of computer-stimulated and 'real world' versions of an interactive
      depth perception task. The availability of depth cues (disparity, accommodation,
      luminance, and texture) was manipulated. Results indicate that ability to
      perceive depth using binocular cues is not associated with ability to perceive
      depth using monocular cues. Further, ability to integrate cues was a strong
      correlate of depth perception when multiple cues were available, and appeared
      more important in this respect than ability to use individual depth cues.
      Correlations between psychometric measures of fluid intelligence/spatial ability
      and depth perception were generally weak, but consistent with the broader pattern
      of results, suggesting that individual differences in depth perception should
      currently be regarded as 'cue specific'. Hypothesized facilitative effects of
      paradoxical monocular stereopsis were not found.

PMID- 9771165
TI  - Exploitation of elasticity in copying geometrical patterns: the role of age,
      movement amplitude, and limb-segment involvement.
AB  - An experiment is reported in which 12 adults and 12 10-year-old children copied
      three-segment geometrical patterns under various size and limb-segment
      involvement instructions. Next to an assessment of movement pauses, analyses of
      pen-tip displacements focused on: (1) the accuracy of size reproduction, (2)
      movement time, and (3) ratio of peak-over-mean velocity. A low value of the
      latter measure was considered to reflect the adoption of a cyclical movement
      regime facilitating the exploitation of elastic properties of muscles and tendons
      during execution. Subjects generally produced size overshoots which, particularly
      for the children, were most pronounced for small patterns. These effects were
      accompanied by prolonged movement times. Peak-over-mean velocity ratios were
      smallest in adults, in large patterns, and when the arm instead of the hand was
      required as effector. Although adults paused more frequently than children, pause
      durations were similar in both groups. It is suggested that fast movements with
      low peak-over-mean velocity ratios reflect successful attempts by subjects to
      exploit the elasticity of muscles and tendons. These attempts are accompanied in
      the present task, however, by an increased risk of having to pause between
      subsequent segments of a movement sequence, possibly for energy-dissipation
      reasons.

PMID- 9771166
TI  - Anaesthesia and electroconvulsive therapy (ECT)

PMID- 9771167
TI  - Continuous microspinal anaesthesia: another perspective on mechanisms inducing
      cauda equina syndrome.
AB  - Continuous spinal anaesthesia through a microspinal catheter technique has been
      criticised on several grounds and is now rarely used. This paper reviews the
      possible causes of the cauda equina syndrome which have been described and, on
      the basis of research in cadaver preparations, a glass 'spine' model and clinical
      experience in over 200 cases, suggests how these problems might be avoided. The
      use of careful insertion techniques, limiting the length of catheter inserted
      into the subarachnoid space and the use of no stronger than 0.5% bupivacaine
      solution are recommended.

PMID- 9771168
TI  - Surgical face masks and downward dispersal of bacteria.
AB  - The ability of face masks to prevent forward dispersal of bacteria is offset by
      the possibility that they may increase vertical shedding of bacteria from the
      face during facial movement. To investigate this, a blood agar plate was placed
      30 cm directly below the lips of 20 volunteers who were encouraged to talk for 20
      min while moving their heads from side to side, without a face mask for the first
      5 min and then with a standard, soft pleated face mask for the subsequent 15 min.
      The agar plates were changed at 5-min intervals. Analysis of the number of
      bacterial colonies grown on each agar plate showed a statistically significant
      reduction in the median number of colonies cultured per plate when the mask was
      worn. Our results suggest that for procedures lasting less than 15 min, the
      operator should wear a face mask, particularly when the face is in close
      proximity to the operative field and the need for speaking is anticipated.

PMID- 9771169
TI  - Anatomical variation of cerebral venous drainage: the theoretical effect on
      jugular bulb blood samples.
AB  - Recent studies have demonstrated significant variation in bilateral jugular
      venous oxygen saturation measurements which may be of clinical significance. We
      have therefore measured variations in normal dural sinus venous drainage to
      assess the possible effects of normal anatomical variations on measured jugular
      venous oxygen saturation. Normal volunteers (n = 25) were imaged using magnetic
      resonance venography to demonstrate variations in venous anatomy. Flow was
      measured in the superior sagittal sinus and bilaterally in the transverse sinus,
      sigmoid sinus proximal to the jugular bulb and proximal jugular vein using phase
      difference magnetic resonance imaging. Examination of magnetic resonance venogram
      images showed considerable variability in the symmetry of transverse sinus flow.
      Complete absence of one transverse sinus was seen in four cases and significant
      asymmetry in the size of the transverse sinuses was present in 13. Quantitative
      flow studies demonstrated that the ratio of superior sagittal sinus to combined
      jugular bulb flow showed remarkably little variation (0.46 +/- 0.06).
      Measurements of transverse sinus flow showed significant asymmetry (< 40% of
      superior sagittal sinus flow in one transverse sinus) in 21 of 25 volunteers. The
      effect of the observed asymmetry on jugular venous oxygen saturation was modelled
      based on the assumption of either a supratentorial or infratentorial lesion. This
      model predicted significant asymmetry in jugular venous oxygen saturation
      measurements (> 10%) in 65% of cases with a supratentorial lesion which is in
      close agreement with clinical observations. This study suggests that normal
      variations in venous drainage may account for observed asymmetry in jugular
      venous oxygen saturation measurements.

PMID- 9771170
TI  - Ambient oxygen concentrations during simulated cardiopulmonary resuscitation.
AB  - Oxygen concentrations were measured at 12 points around a cardiopulmonary
      resuscitation practice mannequin following simulated ventilation with a self
      inflating bag, a 'Waters' bag and a ventilator to determine whether increased
      oxygen concentrations may contribute to the risk of combustion from arcing
      defibrillator paddles. Ventilation was simulated using either a mask or via a
      tracheal tube fitted to the airway. The head of the mannequin rested upon a 10-cm
      high pillow. Gas sampling took place after 5 min of ventilation with subsequent
      removal of the ventilatory device and placement on the pillow to the left of the
      mouth, with the tubing of the device removed to a point 1 m behind the mouth and
      with the device left connected to the tracheal tube. Gas was sampled after using
      all devices at oxygen flows of 10l.min-1 and 15l.min-1. Slightly increased oxygen
      concentrations were noted over the anterior chest after placement of all devices
      on the pillow at the higher flow. Concentrations of greater than 30% were
      measured in the left axilla after placement of all devices on the pillow at both
      flows. No increase in oxygen concentration was seen when the devices were either
      left connected to the tracheal tube or removed to a distance of 1 m. It would
      appear that leaving a patient connected to a ventilator poses no increase in risk
      of fire from ignition of combustible material in an oxygen-enriched atmosphere
      during defibrillation. Disconnecting any device which continues to discharge
      oxygen and leaving it on the pillow before defibrillation is dangerous.

PMID- 9771171
TI  - The effect of potato starch derived and corn starch derived hydroxyethyl starch
      on in vitro blood coagulation.
AB  - We have compared the effects of progressive in vitro haemodilution (30% and 60%)
      with potato starch derived hydroxyethyl starch and corn starch derived
      hydroxyethyl starch on blood coagulation in 80 patients using thrombelastography.
      Both solutions significantly compromised blood coagulation as evidenced by an
      increase in coagulation time and decrease in angle alpha, maximum amplitude and
      coagulation index (p < 0.05). Blood coagulation was more compromised during
      haemodilution with potato starch derived hydroxyethyl starch as compared with
      corn starch derived hydroxyethyl starch (p < 0.05). When taking the effect of
      haemodilution with 0.9% saline into account, haemodilution with both hydroxyethyl
      starch solutions also augmented clot lysis (p < 0.05), with potato starch derived
      hydroxyethyl starch having a greater effect than corn starch derived hydroxyethyl
      starch (p < 0.05). We conclude that potato starch derived hydroxyethyl starch
      compromises in vitro blood coagulation more than corn starch derived hydroxyethyl
      starch.

PMID- 9771172
TI  - Awake intubation of the difficult airway with the intubating laryngeal mask
      airway.
AB  - The intubating laryngeal mask airway is a new device that facilitates intubation
      of the trachea. We assessed its use in 15 awake patients in whom we anticipated
      difficulty with tracheal intubation; we would otherwise have secured the
      patients' airways using a fibreoptic bronchoscope. All patients were sedated and
      had their airways anaesthetised with local anaesthetic. The tracheas of all 15
      patients were successfully intubated. The mean time from start of sedation to
      successful intubation was 10.8 min. The mean time from completion of sedation and
      airway local anaesthesia to tracheal intubation was 2.8 min. Patients remained
      haemodynamically stable throughout, peripheral oxygen saturation was maintained
      and there were no obvious cases of pulmonary aspiration. Most patients complained
      of sore throat and hoarseness. We have demonstrated through this descriptive
      study that the intubating laryngel mask airway may, in certain circumstances, be
      used as an alternative to the fibreoptic bronchoscope.

PMID- 9771173
TI  - Controlled ventilation using isoflurane with an in-circle vaporiser.
AB  - We studied 19 patients anaesthetised for routine surgery using isoflurane
      delivered from a Komesaroff vaporiser mounted within a circle system. Their lungs
      were ventilated using a Penlon Nuffield ventilator attached to the circle system
      by a trunk of tubing. Fresh gas flow rates of 1, 2 or 31.min-1 were used. The
      inspired agent concentration was measured using a Datex Ultima multigas analyser
      and was found to be stable and easily controlled.

PMID- 9771174
TI  - Intermediate care, possibilities, requirements and solutions.
AB  - The inadequate supply of intensive care facilities has focused interest on
      intermediate care as a means of bridging the gulf between the level of support
      available in the intensive care unit and the general ward. However, few hospitals
      have developed intermediate care, in the form of high-dependency care units, and
      little information exists concerning the use or potential of such areas.
      Therefore, this review proposes to cover the definition of intermediate care and
      to discuss some of the possible reasons why intermediate care is now believed
      necessary. The capabilities of intermediate care for selected groups of patients
      and the treatment modalities offered are described. The present provision of high
      dependency care in the United Kingdom is discussed and the methods for estimating
      the required size of a high-dependency unit are outlined. The impact of a high
      dependency unit on the workload of the intensive care unit and the potential cost
      saving of managing such patients in an intermediate care area are illustrated.

PMID- 9771175
TI  - The peri-operative management of atrial fibrillation.
AB  - Atrial fibrillation is a common arrhythmia frequently seen in surgical patients.
      The onset of new atrial fibrillation during the peri-operative period is less
      common. There are many possible precipitating factors, although volatile agents
      themselves may have an antifibrillatory action. The management of atrial
      fibrillation includes removal of any precipitating factors and treatment of the
      arrhythmia itself. Immediate management of acute-onset atrial fibrillation is
      usually direct current cardioversion. Alternatively, anti-arrhythmic drugs can be
      used to achieve cardioversion. In patients with rapid, chronic atrial
      fibrillation or those refractory to cardioversion, priority is given to control
      of the ventricular rate. Thrombo-embolism is a significant risk if atrial
      fibrillation is paroxysmal or persists for more than 48 h.

PMID- 9771176
TI  - Impedance cardiography. The impact of new technology.
AB  - The 1990s have witnessed major advances in impedance cardiography technology.
      Problems existed with the methods used to calculate cardiac output. Excessive
      lung fluid, as often found in critically ill patients, may also invalidate
      measurements. The signal processing and measurement techniques used in older
      systems were deficient. The newer systems, of which there are at least six,
      incorporate novel and improved signal processing techniques. They also offer
      analog visual displays, personal computer interfacing, sophisticated analytical
      software and haemodynamic patient management systems. Evaluation of these systems
      is difficult because no true 'gold standard' method of cardiac output measurement
      exists. When compared with thermodilution techniques, limits of agreement of +/-
      20-30% seem acceptable. These limits can be achieved in normal subjects but not
      in critically ill patients. Validation data are available for only half of the
      new systems. Until recently, the main application for impedance cardiography has
      been research but improved accuracy should lead to increased clinical usage.

PMID- 9771177
TI  - The criminal use of chloroform.

PMID- 9771178
TI  - Epidural haematoma following anticoagulant treatment in a patient with an
      indwelling epidural catheter.
AB  - We report the occurrence of an epidural haematoma after the removal of a lumbar
      epidural catheter, which had been inserted 2 days previously for surgery to
      revise a thrombosed femoral-popliteal graft. Pre-operatively the patient received
      intravenous heparin by infusion, but this was stopped 7 h prior to epidural
      insertion. Coagulation studies were normal. The epidural catheter insertion was
      unremarkable. Postoperatively, the patient received a continuous epidural
      infusion of fentanyl (3 micrograms.ml-1) and bupivacaine (0.0625%), in addition
      to systemic anticoagulant therapy with heparin. On the second postoperative day,
      the patient was noted to have developed bilateral leg weakness (following
      transfer to another department for Doppler studies). The epidural catheter was
      inadvertently removed while the patient was anticoagulated and paraparesis
      developed overnight. After a significant delay, an epidural haematoma was
      diagnosed and treated by decompressive laminectomy. At operation an epidural
      haematoma extending posteriorly from T12 to L3 was removed.

PMID- 9771179
TI  - The use of remifentanil in general anaesthesia for caesarean section in a patient
      with mitral valve disease.
AB  - We report the use of remifentanil as part of a general anaesthetic technique for
      a patient with mixed mitral valve disease, asthma and pre-eclampsia presenting
      for an emergency Caesarean section. The use of remifentanil was associated with
      stable haemodynamic variables during general anaesthesia. No clinically
      significant respiratory depression was noted in the neonate.

PMID- 9771180
TI  - The management of metformin overdose.
AB  - Only two cases of deliberate self-poisoning with metformin have been described in
      the literature. We report the management of three cases, all of which presented
      with severe lactic acidosis. Two cases had a fatal outcome. The options for
      treatment and previous cases reported in the literature are reviewed.
      Recommendations for the management of metformin overdose include early
      recognition, intensive support of the cardiovascular system, the correction of
      metabolic acidosis and the maintenance of body temperature. The use of venovenous
      haemofiltration against a non-lactate containing fluid may improve outcome when
      sodium bicarbonate alone fails to reverse severe systemic acidosis.

PMID- 9771181
TI  - Evaluation of intubating conditions with rocuronium and either propofol or
      etomidate for rapid sequence induction.
AB  - We have assessed the effect of two induction agents on tracheal intubating
      conditions after rocuronium 0.6 mg.kg-1 in unpremedicated patients undergoing
      simulated rapid sequence induction. Following pre-oxygenation, anaesthesia was
      induced with propofol up to 2.5 mg.kg-1 (n = 35) or etomidate 0.3 mg.kg-1 (n =
      36), and further increments as required. After loss of verbal contact, cricoid
      pressure was applied and rocuronium was injected. Laryngoscopy was performed at
      45 s and intubation attempted at 60 s after rocuronium had been given. Ninety
      four per cent of patients in the propofol group had clinically acceptable (good
      or excellent) intubating conditions compared to only 75% in the etomidate group
      (p = 0.025). Owing to coughing, one patient in the etomidate group could not be
      intubated on the first attempt. A greater pressor response also followed
      intubation after induction with etomidate. We conclude that etomidate and
      rocuronium alone cannot be recommended for intubation at 60 s under rapid
      sequence induction conditions.

PMID- 9771182
TI  - The influence of intrathecal fentanyl on the characteristics of subarachnoid
      block for caesarean section.
AB  - Forty healthy parturients scheduled for elective Caesarean section were randomly
      allocated to receive either 0.3 ml 0.9% saline (control group, n = 20), or 15
      micrograms (0.3 ml) fentanyl (treatment group, n = 20) added to 2.5 ml 0.5%
      hyperbaric bupivacaine given intrathecally in the sitting position. A sensory
      block to T4 was achieved after 6.5 min in those who received fentanyl compared to
      8.0 min in the control group; this was not significantly different. The highest
      level of sensory block achieved in both groups was similar. Ephedrine was
      required earlier (p < 0.05) in those who received fentanyl but the total
      requirement of ephedrine intra-operatively was similar. Fentanyl significantly
      improved the quality of intra-operative surgical anaesthesia as none of the
      patients in the treatment group complained of discomfort compared with seven in
      the control group (p < 0.05). Similarly those in the treatment group had better
      comfort scores as evaluated by visual analogue score (p < 0.01). Regression of
      anaesthesia to T12 took longer (184 vs 156 min, p < 0.05) in those who received
      fentanyl but this did not affect the total requirement of morphine in the first
      24 h after operation. There was no difference in the incidence of side effects in
      the mother and no adverse effects were detected in the baby. The results indicate
      that adding 15 micrograms fentanyl to hyperbaric bupivacaine for spinal
      anaesthesia markedly improves intra-operative anaesthesia for Caesarean section.

PMID- 9771183
TI  - Paediatric anaesthesia--who should do it?

PMID- 9771185
TI  - Lingual nerve injury associated with laryngeal mask use.

PMID- 9771184
TI  - Paediatric anaesthesia--who should do it?

PMID- 9771186
TI  - Requirements for target-controlled infusion of propofol to insert the laryngeal
      mask airway.

PMID- 9771187
TI  - A 'his' and 'hers' laryngeal mask?

PMID- 9771188
TI  - Effective use of the cuffed oropharyngeal airway.

PMID- 9771189
TI  - Combitube and percutaneous tracheostomy.

PMID- 9771190
TI  - Multiple trauma and massive blood transfusion.

PMID- 9771191
TI  - Do the risk of combined spinal-epidural analgesia in labour outweigh the
      benefits?

PMID- 9771192
TI  - Intrathecal diamorphine and Caesarean section.

PMID- 9771193
TI  - Checking block height prior to caesarean section.

PMID- 9771194
TI  - Current trends in obstetric epidural practice.

PMID- 9771195
TI  - The demise of nitrous oxide--fine for anaesthesia, but what about sedation?

PMID- 9771196
TI  - ASA scoring revisited to match fitness with competence.

PMID- 9771197
TI  - Use of essential oil to promote induction of anaesthesia in children.

PMID- 9771198
TI  - Chronic spinal cord lesions--don't forget Bier's block.

PMID- 9771199
TI  - Remifentanil in myasthenia gravis.

PMID- 9771200
TI  - Tracheal aerosol administration of salbutamol.

PMID- 9771201
TI  - Application of drugs to the nasal passages.

PMID- 9771202
TI  - Re-inventing the probang?

PMID- 9771203
TI  - A missed opportunity.

PMID- 9771204
TI  - Should we look for osteoporosis in patients with rheumatoid arthritis?

PMID- 9771205
TI  - The Th1-Th2 model--what relevance to inflammatory arthritis?

PMID- 9771206
TI  - Postural changes, dysphagia, and systemic sclerosis.

PMID- 9771207
TI  - A method for estimating macromolecular reflection by human synovium, using
      measurements of intra-articular half lives.
AB  - Recent studies show that very large macromolecules in synovial fluid, such as
      hyaluronan and large proteoglycans, are partially reflected by the synovial
      lining during fluid drainage, and thus selectively retained within the cavity.
      Size selective molecular reflection is a fundamental property of membranes, and a
      method for quantifying the reflective behaviour of human synovium could be of
      value in several pathophysiological areas. The method proposed here is based on
      the intra-articular half lives of the macromolecule of interest and of a smaller,
      easily cleared protein such as albumin. The key relation is derived from the law
      of conservation of mass, using simple algebra. It is found that, when the intra
      articular half lives of albumin and a macromolecular test solute are determined
      simultaneously, the reflected fraction of the test solute is given by the
      complement of the half life ratio. Examples are given. Intra-articular half lives
      can thus be used to consider such questions as whether immune complexes are
      significantly reflected by the synovial surface, how the reflective property
      changes in arthritides or with treatment, and how significantly reflection might
      influence the intra-articular concentration of large "markers" of joint disease
      activity.

PMID- 9771208
TI  - Effects of cyclical etidronate combined with calcitriol versus cyclical
      etidronate alone on spine and femoral neck bone mineral density in postmenopausal
      osteoporotic women.
AB  - OBJECTIVES: Few data are available on the effects of combination therapy for the
      treatment of osteoporosis. The aim of this study was to compare the effects of
      intermittent cyclical etidronate (E) therapy alone with a combination of cyclical
      etidronate and calcitriol (E + C) on spine and femoral neck bone mineral density
      (BMD) at one year. METHODS: Postmenopausal women with at least one non-traumatic
      vertebral fracture or z score < -1.5 were randomly allocated to an E group (each
      cycle = oral etidronate 400 mg daily for 14 days followed by calcium 500 mg daily
      for 76 days) or an E + C group (as for E plus oral calcitriol 0.5 microgram
      daily). Lumbar spine and femoral neck BMDs were measured by dual energy x ray
      absorptiometry at baseline and at one year. The study design did not contain a
      placebo group. RESULTS: The mean % increase in lumbar spine BMD was 5.2% (95% CI
      = 3.4 to 7.0) in the E + C group (n = 24), which was significantly greater than
      the 2.7% (95% CI = 1.3 to 4.1) increase in the E group (n = 23) (p < 0.05). The
      femoral neck BMD in the E + C group increased by 2.0% (95% CI = 0.8 to 3.2),
      which was significantly different from the E group where there was a -0.4% (95%
      CI = -2.4 to 1.6) change (p = 0.046). CONCLUSIONS: These data show that a
      combination of cyclical etidronate and calcitriol is better than cyclical
      etidronate alone in terms of changes in BMD at both spine and femoral neck sites.
      Although further data are needed on fracture efficacy, this study suggests that
      combination therapies have additive therapeutic potential that may exceed that
      expected from their theoretical mode of action.

PMID- 9771209
TI  - Magnetic resonance imaging of the wrist in early rheumatoid arthritis reveals a
      high prevalence of erosions at four months after symptom onset.
AB  - OBJECTIVES: To evaluate the role of magnetic resonance imaging (MRI) of the wrist
      in detecting early joint damage in patients with rheumatoid arthritis (RA).
      METHODS: MRI was performed on 42 patients with early RA (median symptom duration
      of four months). Scans were scored separately by two musculoskeletal radiologists
      using a newly devised scoring system, which was validated. MRI findings were
      compared with plain radiography, clinical measures, and HLA-DRB*01/04 genotyping.
      RESULTS: Interobserver reliability for the overall MRI score was high (r = 0.81)
      as was intraobserver reliability (r = 0.94 for observer 1 and 0.81 for observer
      2). There was more variation in scoring synovitis (interobserver reliability: r =
      0.74). Erosions were detected in 45% of scans (19 of 42), compared with 15% of
      plain radiographs. The most common site for erosions was the capitate (39%), for
      synovitis the ulnar aspect of the radiocarpal joint, and for tendonitis, the
      extensor carpi ulnaris tendon. The total MRI score and MRI synovitis score
      correlated most significantly with C reactive protein (r = 0.40 and 0.42
      respectively, p < 0.01). The MRI erosion score was highly correlated with MRI
      bone marrow oedema (r = 0.83) as well as the Ritchie score and disease activity
      score (r = 0.32, p < 0.05). HLA-DRB1*04 or *01 (shared epitope +ve) was found in
      76% of patients; 84% of those with MRI erosions and 69% of those without (NS, p =
      0.3). CONCLUSIONS: A high proportion of RA patients develop MRI erosions very
      early in their disease, when plain radiography is frequently normal. MRI of the
      dominant wrist may identify those requiring early aggressive treatment.

PMID- 9771210
TI  - Ultrasound and operative evaluation of arthritic shoulder joints.
AB  - OBJECTIVE: To assess the diagnostic value of ultrasonography (US) in the
      evaluation of arthritic shoulder joints. METHODS: Twenty shoulders of 20
      inpatients with arthritis were evaluated by US one day before the shoulder
      operation. Changes in the subacromial-subdeltoid bursa, biceps tendon and tendon
      sheath, rotatof cuff, and glenohumeral joint were recorded and compared with
      findings at operation. RESULTS: In the detection of effusion/hypertrophy in the
      subacromial-subdeltoid bursa, US had a sensitivity of 93% and a specificity of
      83%. For a biceps tendon rupture US had a sensitivity of 70% and a specificity of
      100%. US missed three intraarticular biceps tendon ruptures. For
      effusion/hypertrophy in the biceps tendon sheath US had a sensitivity of 100% and
      a specificity of 83%. For a rotator cuff tear US had a sensitivity of 83% and a
      specificity of 57%. US missed two small longitudinal rotator cuff tears. Three
      thin membranous, but intact, rotator cuff tendons were classified as full
      thickness tears by US. Synovial effusion/hypertrophy was detected by US and at
      operation in all of the 12 glenohumeral joints that were evaluable at surgery.
      CONCLUSION: US is a reliable method in experienced hands for the evaluation of
      inflammatory changes of an arthritic shoulder. In advanced stages of rheumatoid
      shoulder joints, however, US is not useful, because destructive bone changes and
      tendon ruptures change the normal anatomy and restrict shoulder motions, limiting
      the visibility of US.

PMID- 9771211
TI  - Linkage of cytokine genes to rheumatoid arthritis. Evidence of genetic
      heterogeneity.
AB  - OBJECTIVE: To investigate linkage of candidate disease susceptibility genes to
      rheumatoid arthritis (RA) in affected sibling pair families stratified for
      specific clinical features. METHOD: Two hundred RA affected sibling pair families
      were genotyped for informative microsatellite markers mapping within or less than
      3cM from: INF alpha, INF gamma, INF beta, IL1 alpha, IL1 beta, IL1R, IL2, IL6,
      IL5R, IL8R, BCL2, CD40L, NOS3, NRAMP, alpha 1 anti-trypsin, and alpha 1 anti
      chymotrypsin, using fluorescence based automated technology. Linkage was examined
      by defining allele sharing sibling pairs. This was assessed by maximum likelihood
      inheritance by descent methods. RESULTS: An increase in allele sharing was seen
      for IL5R in female sibling pairs (LOD 0.91, p = 0.03), for INF gamma in sibling
      pairs with an affected male (LOD 0.96, p = 0.03) and most significantly for IL2
      in sibling pairs where one or both were persistently seronegative (LOD 1.05, p =
      0.02). CONCLUSION: Weak evidence of linkage of RA to IL5R, IFN gamma, and IL2 has
      been detected in clinical subsets of sibling pairs suggesting that RA is a
      genetically heterogeneous disease.

PMID- 9771212
TI  - Immunoglobulin allotype gene polymorphisms in systemic sclerosis: interactive
      effect of MHC class II and KM genes on anticentromere antibody production.
AB  - OBJECTIVE: To examine potential interactions between immunoglobulin (Ig)-allotype
      gene polymorphisms and susceptibility to systemic sclerosis (SSc) as well as
      serological expression in SSc patients. METHODS: IgG heavy chain allotypes G1M(f,
      z), G2M(n+, n-), G3M(b, g) and Ig light chain allotype KM(1, (1, 2), 3) were
      genotyped in 105 Japanese SSc patients and 47 race matched normal controls using
      polymerase chain reaction (PCR) based methods. Associations of each Ig allotype
      with SSc related antinuclear antibodies were examined in combination with or
      without MHC class II alleles. RESULTS: GM/KM genotypic and allelic frequencies
      were similar in SSc patients and in normal controls. Frequencies of G1M(f) and
      G2M(n+) were significantly decreased in anticentromere antibody (ACA) positive
      SSc patients compared with ACA negative SSc patients (p = 0.04 and 0.02,
      respectively). Conversely, the presence of DQB1*0501 and KM(1, 2) significantly
      increased the risk of ACA positivity. CONCLUSION: Ig allotype gene polymorphisms
      were not associated with susceptibility to SSc. Instead, the results suggested
      that MHC class II and KM genes are associated with autoimmune responses by
      interactively promoting the production of ACA.

PMID- 9771213
TI  - A genetic association study of the IGF-1 gene and radiological osteoarthritis in
      a population-based cohort study (the Rotterdam Study).
AB  - OBJECTIVE: A genetic association study was performed to investigate whether
      radiographical osteoarthritis (ROA) was associated with specific genotypes of the
      insulin-like growth factor I (IGF-1) gene. METHODS: Subjects aged 55-65 years
      were selected from a population-based study of which ROA at the knee, hip, spine,
      and hand was assessed. Genotypes were determined of a polymorphism in the
      promoter region of the IGF-1 gene. RESULTS: The IGF-1 locus was significantly
      associated with the presence of ROA (over-all adjusted OR for heterozygous
      subjects = 1.9, 95% CI 1.2, 3.1 and for homozygous subjects 3.6, 95% CI 0.8,
      16.2). CONCLUSION: These results suggest that variation at the IGF-1 locus is
      associated with ROA development and may play a part in ROA pathogenesis. To
      confirm these findings replication in another population-based sample is needed.

PMID- 9771214
TI  - Low frequency of recent parvovirus infection in a population-based cohort of
      patients with early inflammatory polyarthritis.
AB  - OBJECTIVE: To determine the contribution of human parvovirus B19 infection in
      explaining the incidence of early inflammatory polyarthritis (IP) in a
      population. SETTING: The Norfolk Arthritis Register (NOAR) is a community-based
      programme aiming to ascertain all new cases of IP arising in a population that
      lead to attendance at primary care. SUBJECTS: 147 newly ascertained subjects with
      IP with a disease duration of less than 16 weeks. METHODS: Full clinical
      appraisal of all subjects who were followed up for three years. B19 IgM assayed
      with a third generation antibody capture enzyme immunoassay. RESULTS: Only four
      (2.7%) patients had evidence of recent B19 infection, only one of whom did not
      satisfy criteria for rheumatoid arthritis (RA). CONCLUSION: B19 infection does
      not explain more than a small proportion of either RA or undifferentiated IP
      cases occurring in the population.

PMID- 9771215
TI  - Prescribing by general practitioners after an osteoporotic fracture.
AB  - OBJECTIVES: Osteoporosis is a major cause of morbidity and cost. Patients
      sustaining one osteoporotic fracture are at increased risk of having another
      fracture. The objective of this study was to examine the use of "bone drugs" for
      the prevention of further osteoporotic fractures among patients who have had a
      "typical" osteoporotic fracture. METHODS: This study took a random sample of 300
      women aged 50 and over who had sustained either a vertebral, hip or Colles
      fracture in 1995 from the General Practice Research Database (GPRD) and compared
      their use of bone drugs with 300 age and practice matched controls. RESULTS:
      Compared with age and practice matched control patients only vertebral fracture
      patients showed a statistically significant increase in the use of bone drugs in
      the year after fracture (39% and 2% for cases and controls respectively; 95% CI
      of difference 27% to 47%). Etidronate was the most commonly used compound.
      CONCLUSION: The majority of patients sustaining an osteoporotic fracture are not
      prescribed any pharmaceutical agents for the secondary prevention of fracture one
      year after a primary fracture.

PMID- 9771216
TI  - Relation between HLA DRB1 alleles and corticosteroid resistance in giant cell
      arteritis.
AB  - OBJECTIVE: To evaluate the clinical usefulness of genomic HLA typing during the
      first two years of established giant cell arteritis (GCA). METHODS: HLA typing
      was performed by PCR-SSO in 41 selected white patients with GCA confirmed by
      biopsy. Patient data were compared with those of a control group of 384 bone
      marrow donors (relative risk, p value and chi 2 test for each allele). Clinical
      features at onset and response to treatment over a two year period were evaluated
      in relation to the genetic pattern. RESULTS: DRB1*04 was significantly increased
      in the GCA group (frequency of 48.78% compared with 19.79% in controls, p <
      0.001). The distribution of the DRB1*04 subtypes in the GCA group was similar to
      that in controls. No clinical or biological differences were found in association
      with HLA at the time of diagnosis. Over the two year follow up, nine patients
      presented resistance to corticosteroid treatment and eight of these (88.88%) had
      DRB1*04 (p < 0.001). CONCLUSIONS: GCA seems to be associated with HLA DRB1*04
      (regardless of the subtype) and this association appears to be accompanied by
      corticosteroid resistance, suggesting that genomic typing may be useful to
      identify patients eligible for early alternative treatment to corticosteroid
      drugs.

PMID- 9771217
TI  - Ultrasound guided injection of recalcitrant plantar fasciitis.
AB  - OBJECTIVE: To determine the effect of ultrasound guided injection in recalcitrant
      idiopathic plantar fasciitis. METHODS: Four patients with a clinical diagnosis of
      idiopathic plantar fasciitis, who were unresponsive to palpation guided injection
      with triamcinolone acetonide and local anaesthetic, underwent ultrasonographic
      examination of the heel. RESULTS: The following ultrasonographic features were
      noted:- (a) increased thickness of plantar fascia in symptomatic heels compared
      with asymptomatic heels, (b) loss of distinction of the distal plantar fascia
      borders, (c) reduced echogenicity of the plantar fascia. Ultrasound guided
      injection of the enlarged, hypoechoic plantar fascia resulted in complete relief
      in four of five heels (mean duration of follow up = 24 months) in three cases.
      One patient developed a recurrence of symptoms after six months. CONCLUSION:
      Ultrasound allows for confirmation of the clinical diagnosis and ultrasound
      guided injection produces a good clinical response when unguided injection is
      unsuccessful. The technique is quick, inexpensive, and entails no radiation
      exposure.

PMID- 9771218
TI  - Role of endoscopic ultrasound in the preoperative assessment of patients with
      oesophageal cancer.
AB  - Despite encouraging results from Europe and America, endoscopic ultrasound (EUS)
      has yet to become established in the United Kingdom. The aims of this prospective
      study were to investigate its value in the assessment of patients with benign and
      malignant oesophageal conditions, and in particular to assess its reliability for
      local tumour (T) and lymph node (N) staging in patients with oesophageal cancer.
      EUS was performed in 90 patients: 23 were normal controls, 17 had benign
      oesophageal diseases and 50 had operable oesophageal cancer. Detailed
      measurements of the oesophageal wall and regional nodes were made and the
      accuracy of EUS for locoregional tumour staging was compared with final
      histology. EUS visualised the normal oesophageal wall as a multilayered
      structure, thicker distally than proximally. Distal stenotic conditions caused
      thickening of the proximal wall and loss of this gradient. EUS was highly
      accurate for both local tumour (92% correct) and lymph node staging (86% correct)
      and was better than computed tomography, magnetic resonance imaging and open
      staging performed by the surgeon. Fine needle aspiration biopsy using radial
      scanning EUS guidance was shown to be feasible. EUS is a valuable technique for
      investigation of both benign and malignant oesophageal conditions. It provides
      highly accurate local tumour and regional lymph node staging data in patients
      with oesophageal cancer.

PMID- 9771219
TI  - Gastrostomy complications in infants and children.
AB  - Thirty children have had percutaneous endoscopic gastrostomy (PEG) inserted for
      feeding purposes. During a follow-up period of 5-45 months (mean 24 months),
      complications were recorded in 13 patients. Some patients had more than one
      complication. Complications included colocutaneous fistula, gastro-oesophageal
      reflux, wound infection, granulation tissue formation, tube leakage, tube
      blockage and bleeding. The authors present a retrospective review of the results
      and discuss the management of these complications.

PMID- 9771220
TI  - Use of hepatic imaging techniques in the management of colorectal cancer: a
      survey of current practice among surgeons in the northwest of England.

PMID- 9771221
TI  - Causes of late diagnosis in cases of colorectal cancer seen in a district general
      hospital over a 2-year period.
AB  - Our aim in this prospective study was to identify those patients who were found
      to have a colorectal cancer after a delay we considered unacceptable; this was
      taken as 6 months or more from initial presentation to a physician to diagnosis.
      It was then possible to determine the presenting complaints (always multiple) and
      the reasons for delay, in the hope that recommendations could be made regarding
      appropriate, rapid and thorough investigation of patients suspected of having a
      colorectal cancer. Of the total of 141 patients with colorectal cancer (108
      elective, 33 emergency cases) under the care of one consultant during the period
      studied, 17 patients (12%) (10 men and 7 women), satisfied the criteria for late
      diagnosis. The mean age was 72.4 years (range 43-86 years). Five common
      presenting complaints were identified. They were, symptomatic iron deficiency
      anaemia, rectal bleeding, change in bowel habit, abdominal pain and weight loss.
      Incomplete imaging of the colon in patients with sinister presenting symptoms was
      the most commonly identified factor in delay of diagnosis. Inappropriate iron
      therapy and false-negative reporting of double contrast barium enema
      investigations were both seen in a number of cases. Other causes were,
      inappropriate surgical treatment and both clerical error and delay. The mean time
      for delay was 17.6 months (median 15 months). Late diagnosed cancers were most
      commonly found in the caecum and least commonly in the rectum. Colonic tumours of
      each Dukes' stage were identified, Dukes' B most common and Dukes' A least.

PMID- 9771222
TI  - An ileal enterotomy for colonic lavage and primary anastomosis in left colon
      obstruction also used to defunction the anastomosis.

PMID- 9771223
TI  - Definitive repair of anovaginal fistula in Crohn's disease.
AB  - Anovaginal fistula may be a very distressing complication of Crohn's disease. We
      review the definitive repair of such fistulas in ten patients. The objectives
      were to cure the fistula, maintain continence and avoid proctectomy. The fistula
      was low trans-sphincteric in five patients, high trans-sphincteric in three and
      suprasphincteric in two. Loop ileostomies were formed in nine patients. Overall,
      after 14 repair procedures 8/10 fistulas are healed. Seven remain healed at a
      mean of 38 months (range 10-66 months) after ileostomy closure (six) or repair
      without ileostomy (one). All of the patients are continent. Definitive repair is
      effective and worthwhile in selected patients with Crohn's anovaginal fistula.

PMID- 9771224
TI  - Ultrasound-guided Tru-cut biopsy of the breast.
AB  - Ultrasound-guided automated Tru-cut needle biopsy may be used as an alternative
      to fine needle aspiration cytology for the assessment of discrete mass lesions of
      the breast. This is a retrospective study of 187 biopsies, comparing the results
      with a final diagnosis obtained from subsequent excision or outpatient follow-up.
      Biopsies were performed using a spring-loaded gun under ultrasound guidance.
      Invasive malignancy was demonstrated in 114 biopsies, 98 of which were subjected
      to surgery, with no false-positives. Twelve biopsies contained 'atypical cells',
      pre-invasive malignancy or risk factors for invasive carcinoma, ten of which
      proved to be invasive malignancy on excision. Normal or benign tissue was found
      in 61 biopsies, but of those that proceeded to excision biopsy, 16 were invasive
      or in situ carcinoma. The sensitivity of the procedure for detecting significant
      pathology was 88.7%, and the specificity 100%. When used as part of triple
      assessment, the sensitivity increases to 97.9%. Ultrasound-guided Tru-cut needle
      biopsy is a well-tolerated and reliable procedure for providing a tissue
      diagnosis of malignancy before definitive treatment, and obviating the need for
      formal excision biopsy of lesions for which there is a low index of suspicion.

PMID- 9771225
TI  - The modified B-mammoplasty incision: an alternative skin-conserving technique for
      mastectomy with immediate breast reconstruction.
AB  - A modification of the B-mammoplasty incision (originally described by Regnault
      for reduction mammoplasty) is presented for patients undergoing skin-conserving
      mastectomy and reconstruction. This approach has several advantages; not only
      does it facilitate good exposure for the oncological surgeon to carry out the
      mastectomy, but it can easily be extended into the axilla to allow nodal
      clearance and microvascular access. It creates a suitable pocket into which a
      flap can be tailored or implant/expander inserted, and further adjustment of the
      breast size or shape can be undertaken easily. Most importantly, the scar is
      confined to the infralateral aspect of the breast, leaving the aesthetically
      important upper and medial breast skin scar free.

PMID- 9771226
TI  - Maximum surgical blood ordering schedule in a district general hospital saves
      money and resources.
AB  - A 6-month prospective audit was carried out in three surgical departments of a
      district general hospital. Over that period, 2720 units of red cells were
      electively cross-matched, 957 being transfused. The overall cross-match-to
      transfusion ratio (CTR) was 2.8, but this varied from over 40 for some
      gynaecological procedures to 1.5 for major surgical procedures. The average CTR
      for general surgery was 2.2, orthopaedics 2.3, and obstetrics and gynaecology
      5.7. A maximum surgical blood ordering system (MSBOS) was introduced and a second
      6-month audit carried out. The number of units cross-matched had fallen by 36% to
      1746, with a CTR of 1.8. The change in activity had led to a saving
      conservatively estimated at 11,616.00 Pounds per annum. Local audit and the
      introduction of a MSBOS in a district general hospital is an exercise which can
      demonstrate inefficiencies in blood ordering practices and can lead to large
      financial savings without detracting from standards of patient care.

PMID- 9771228
TI  - Doppler forceps: an instrument to identify vessels during surgical dissection.

PMID- 9771227
TI  - Closed rupture of the posterior tibial artery secondary to a soccer injury.
AB  - Arterial damage following blunt trauma is uncommon and is usually the result of
      high-energy injury. We report a case of posterior tibial artery rupture after a
      closed distal tibial fracture, sustained during a low-energy soccer tackle.

PMID- 9771230
TI  - The Norwich sebaceous cyst in surgical training.

PMID- 9771229
TI  - The motivation to learn: efficacy and relevance of the Oswestry postgraduate
      orthopaedic training programme.
AB  - The efficacy and relevance of medical education has come under increased scrutiny
      in recent years. The shortening of basic surgical training and the introduction
      of 'seamless' higher surgical training has placed greater emphasis on the quality
      of education provided/facilitated by trainers. Additionally, study leave budgets
      are under increasing pressure from trainees wishing to attend courses or
      conferences, and regional postgraduate deans who wish to see a proportionally
      greater amount of training on an 'in-house' basis. Against this background we
      have reviewed the learning opportunities available on the Oswestry postgraduate
      programme to see if these opportunities provide adequate motivation to learn for
      the trainee.

PMID- 9771231
TI  - The Chichester diagnostic peritoneal lavage simulator.

PMID- 9771232
TI  - Persistent drooling: treatment by bilateral submandibular duct transposition and
      simultaneous sublingual gland excision.
AB  - Persistent drooling in a neurologically impaired patient is often multifactorial
      and various treatment modalities have been employed to overcome this distressing
      condition. This study analysed the outcome after bilateral submandibular duct
      transposition and simultaneous sublingual gland excision in 20 patients with
      persistent drooling treated between January 1989 and July 1994. Twelve were male
      and eight were female and were aged 5 years to 40 years. The outcome was
      considered much better/excellent in 11 cases (55%), better/good in eight cases
      (40%), no significant improvement in one case (5%) and none were considered worse
      after the procedure, in the 'early' postoperative period. Long-term results,
      judged by an 18-point questionnaire sent to the carers after an average duration
      of 3.2 years post-operatively, were available for 19 patients. In all, 16 carers
      (84%) felt the drooling had significantly reduced, and three carers (16%) felt
      that there was no improvement. The three patients who were considered not to have
      improved were all found to have made a 'good' improvement in the early post
      operative period. The morbidity associated with the procedure was of a mild and
      transient nature and there was a complete absence of ranula formation in our
      series. The procedure was well accepted by the carers, who were also willing to
      recommend the procedure to others with a similar problem.

PMID- 9771233
TI  - A survey of consultants treating upper aerodigestive tract cancer in the UK.
AB  - A study was undertaken to determine the current service provision for the
      treatment of upper aerodigestive tract (UAT) cancers in the UK. A postal
      questionnaire was sent to all consultant members of relevant specialist
      societies, with 1041 (74%) responding. Treatment of UAT cancer is widely
      dispersed with over 900 consultants from five major disciplines treating, on
      average, less than 10 cases per year. There were few regional or provider
      differences in the facilities and services available and in processes used for
      assessing patients. There is little systematic collection of data for audit or
      research and some consultants do not record stage. The involvement of other
      disciplines in the assessment process, use of joint clinics, counselling,
      specialist nursing and therapy services appears to be low. There is a need for
      rationalisation of head and neck cancer services; for more systematic collection
      of data for audit and research and for improvements in the use of joint clinics
      and support services.

PMID- 9771234
TI  - A randomised trial of the durability of non-allergenic latex-free surgical gloves
      versus latex gloves.
AB  - A prospective randomised trial was performed to compare the robustness of a new
      non-latex surgical glove with a standard latex glove when worn by four general
      surgeons in a district general hospital. Gloves were retrieved after surgery and
      examined using the European Standard Test for punctures. The overall puncture
      rate was 10.1%, and there was no significant difference in the rates between the
      two types of glove, although punctures in the non-latex glove tended to be larger
      and more readily noted by the wearer. The increase in latex allergy among health
      care staff dictates the need for gloves made from other materials, which may also
      be useful for operations on latex-allergic patients.

PMID- 9771235
TI  - A novel method for the assessment of the accuracy of diagnostic codes in general
      surgery.
AB  - The aim of this study was to describe the accuracy of diagnostic coding in
      general surgery in a district general hospital, the North Staffordshire Hospital
      NHS Trust (NSHT), Stoke-on-Trent. An assessment was carried out by comparison
      between codes ascribed by hospital coders and expert external coders. Patients
      who had a finished consultant episode (FCE) in the specialty of general surgery
      at NSHT were included in the study. The sampling frame was general surgery FCEs
      at NSHT purchased by North Staffordshire Health Authority (NSHA) with an episode
      end date between 1 May 1995 and 31 December 1995. Every 15th record was sampled.
      Of 455 records sampled, 157 (35%) were in active use and were excluded but not
      replaced; therefore, 298 (65%) records were studied in detail. Outcome was
      measured by the accuracy of primary diagnostic codes ranked 1, 2, 3, 4, from
      highest to lowest levels of inaccuracy; a description of where errors occurred in
      the data cycle was recorded. Errors were found in 87/298 (29%) records; 25/298
      (8%) records had an error at the highest level (i.e. wrong ICD-10 chapter), and
      44/298 (15%) at the third level. Of the errors, 68/87 (78%) occurred between the
      medical record and the admission form. A substantial percentage (29%) of records
      had inaccurate diagnostic codes. It is concluded that coding should be carried
      out from the medical record rather than from the admission form (KMR1). The
      proportion of records with errors suggests that a routine data coding audit would
      be useful to improve the accuracy of routine diagnostic codes.

PMID- 9771236
TI  - Urinalysis before joint arthroplasty. To dipstick or not? That is the question.

PMID- 9771237
TI  - Complications of laparoscopic surgery.

PMID- 9771238
TI  - Minimum standards for the management of cleft lip and palate: efforts to close
      the audit loop.

PMID- 9771239
TI  - Which primary total knee replacement?

PMID- 9771240
TI  - Hazards of a 'healthy' diet.

PMID- 9771241
TI  - Iatrogenic oesophageal perforations: a clinical review.

PMID- 9771242
TI  - Withdrawing and withholding treatment: comments on new guidelines.

PMID- 9771243
TI  - Toddler diarrhoea: more a nutritional disorder than a disease.

PMID- 9771244
TI  - A randomised, placebo controlled trial of inhaled salbutamol and beclomethasone
      for recurrent cough.
AB  - AIMS: To test the hypothesis that inhaled salbutamol or beclomethasone will
      reduce the frequency of cough in children with recurrent cough. A secondary aim
      was to determine if the presence of airway hyperresponsiveness (AHR) can predict
      the response. DESIGN: Randomised, double blind, placebo controlled trial.
      METHODS: During a coughing phase, 43 children (age 6-17 years) with recurrent
      cough were randomised to receive inhaled salbutamol or placebo (phase I) for 5-7
      days and then beclomethasone or placebo (phase II) for 4-5 weeks, and in a
      subgroup of children for 8-9 weeks. The children used an ambulatory cough meter,
      kept cough diaries, and performed the capsaicin cough sensitivity, hypertonic
      saline bronchoprovocation, and skin prick tests. RESULTS: Salbutamol or
      beclomethasone had no effect on cough frequency or score, irrespective of the
      presence of AHR. CONCLUSIONS: Most children with recurrent cough without other
      evidence of airway obstruction, do not have asthma and neither inhaled salbutamol
      nor beclomethasone is beneficial.

PMID- 9771245
TI  - Treatment of acute asthmatic exacerbations with an increased dose of inhaled
      steroid.
AB  - OBJECTIVE: To investigate the efficacy of an increased dose of inhaled steroid
      used within the context of an asthma self management plan for treating
      exacerbations of asthma. DESIGN: Randomised, double blind, placebo controlled,
      crossover trial. METHODS: Twenty eight children aged 6-14 years with asthma of
      mild to moderate severity were studied for six months. Eighteen pairs of
      exacerbations were available for analysis, during which subjects took an
      increased dose of inhaled steroids or continued on the same dose. RESULTS: There
      was no significant difference between increasing inhaled steroids or placebo on
      morning or evening peak expiratory flow rates (PEFRs), diurnal peak flow
      variability, or symptom scores in the two weeks following an asthma exacerbation.
      Difference (95% confidence intervals) in baseline PEFR on days 1-3 were 3.4% (
      3.5% to 10.4%) and -0.9% (-4.7% to 2.9%) for inhaled steroid and placebo,
      respectively. Spirometric function and the parents' opinion of the effectiveness
      of asthma medications at each exacerbation were also not significantly different
      between inhaled steroid or placebo. CONCLUSION: This study suggests that
      increasing the dose of inhaled steroids at the onset of an exacerbation of asthma
      is ineffective and should not be included in asthma self management plans.

PMID- 9771246
TI  - Prediction of lung function in the inadequately nourished.
AB  - BACKGROUND: In animal models, nutritional deficiency leads to profound
      qualitative changes in the lung beyond an effect on organ size. Although lung
      growth is non-isotropic, predictive values for spirometric lung function in
      children are corrected for height alone. Prediction of lung function should
      consider isotropic growth and nutritional status concurrently. AIM: To establish
      whether nutritional status influences lung function following the exclusion of
      the effect of isotropic growth. METHODS: Nutritional status (weight, body mass
      index, mid-upper arm circumference, and subscapular and triceps skinfold
      thicknesses) was assessed, and lung function (forced vital capacity (FVC), forced
      expiratory volume in one second (FEV1), and peak expiratory flow rate (PEFR) was
      measured in 391 healthy school age children with normal respiratory history and
      examination in a rural setting in West Bengal, India. RESULTS: Lung function
      normalised for sitting height and stature correlated significantly with indices
      of nutrition in both sexes. Adding weight as an independent variable to sitting
      height, new reference prediction equations for FEV1, FVC, and PEFR were
      calculated. CONCLUSIONS: Nutritional differences influence qualitative aspects of
      lung development in childhood beyond simple isotropic lung growth. Prediction of
      lung function must take account of these differences if change as a result of
      disease is to be accurately measured. The identification and correction of
      relevant dietary deficiencies might help to improve lung function in children.

PMID- 9771247
TI  - Clinical and laboratory findings in referrals for mitochondrial DNA analysis.
AB  - BACKGROUND: Increasingly, mutations of mitochondrial DNA (mtDNA) are being
      considered when investigating the aetiology of neurological diseases in
      childhood. However, they are often difficult to predict clinically. METHOD:
      Mitochondrial DNA analysis was carried out on 190 children from 1992 to 1996.
      Most patients were screened for large scale rearrangements and point mutations at
      nucleotide positions 3243, 3271, 8344, and 8993. RESULTS: Mutations were found in
      only 15 patients (7.9%) and were either large scale rearrangements (seven
      patients) or point mutations at nucleotide position 3243 (eight patients). Other
      point mutations were screened for depending on the clinical picture. The age of
      symptom onset was significantly older in children with an mtDNA mutation (mean
      7.0 years) compared with children without a mutation (mean 2.8 years). Neither
      Leigh's syndrome (28 cases) nor severe infantile lactic acidosis (12 cases) was
      associated with mtDNA mutation. Only three clinical features were significantly
      associated with an mtDNA mutation: progressive external ophthalmoplegia,
      myopathy, and pigmentary retinopathy. Family history was valuable: the point
      mutation at nucleotide 3243 (but not the large scale rearrangements) was
      associated with maternal inheritance; and consanguinity was not associated with
      mtDNA mutations. The only investigation that provided specific evidence of an
      underlying mtDNA mutation was histochemical staining of muscle biopsy specimens.
      The large scale mutations associated with Kearns-Sayre syndrome and progressive
      external ophthalmoplegia were found in DNA from muscle only, not leucocyte DNA;
      whereas point mutations were found in leucocyte DNA. CONCLUSIONS: Even among
      children seen at a neurogenetic referral centre, mtDNA mutations were very
      uncommon. Muscle biopsy was the only investigation to provide evidence of mtDNA
      abnormality.

PMID- 9771248
TI  - Infant growth and aorta total lipid fatty acids.
AB  - Abnormal fetal and infant growth have increasingly been correlated with adult
      onset cardiovascular disease. To date, there is little known about the lipid
      fatty acid profiles in infant cardiovascular tissue. Therefore, we analysed total
      lipid fatty acids from thoracic and abdominal aorta intima and media from 24
      normally grown sudden infant death syndrome cases. Aorta from small for
      gestational age (n = 2), failure to thrive from birth (n = 3), and premature (n =
      1) infants were also examined. Dihomo-gamma-linolenic acid (C20:3n-6) and oleic
      acid (C18:1n-9) concentrations were significantly lower in the thoracic than in
      the abdominal aorta. Similar dietary related differences were found in the
      subgroup (n = 15) of infants fed on formula milks. Both abdominal and thoracic
      intimal arachidonic (C20:4n-6) to dihomo-gamma-linolenic acid ratios were greater
      in the infants with retarded growth after birth than in their normally grown
      counterparts. Growth restriction in infancy might disrupt the normal accretion of
      vascular endothelial polyunsaturated fatty acids.

PMID- 9771249
TI  - Bladder dysfunction and neurological disability at presentation in closed spina
      bifida.
AB  - Congenital closed spinal anomalies are associated with distortion of the spinal
      cord, the spinal nerve roots or both, and can result in neurological
      abnormalities of the lower limbs and neuropathic bladder dysfunction. This study
      reports clinical and videourodynamic findings in a group of 51 patients with
      closed spina bifida. The mean age at presentation to a specialist neurological
      clinic was 3.3 years. Twenty five patients presented with urinary tract
      disturbance and 12 presented with neurological problems. Thirty three had normal
      neurological examination or only minor objective signs, 21 had normal renal tract
      ultrasonography but only two patients had normal videourodynamics, with 31 having
      two or more abnormalities during this assessment. Neither clinical neurological
      assessment nor the history of voiding behaviour are reliable indicators of
      bladder dysfunction and subsequent risk of renal damage. Therefore, all patients
      with a known or suspected diagnosis of closed spina bifida should have
      videourodynamic assessment.

PMID- 9771250
TI  - Neuroimaging and spectroscopy in children with epileptic encephalopathies.
AB  - AIMS: To investigate the nature of the unifocal cortical abnormalities on FDG
      positron emission tomography (PET) in children with an epileptic encephalopathy
      but no focal abnormality on electroencephalogram or standard magnetic resonance
      imaging (MRI). METHODS: Repeat FDG PET, surface rendered high resolution MRI, and
      single voxel magnetic resonance proton spectroscopy of the areas of abnormal
      metabolism compared to the contralateral side in 11 children aged 2 to 12 years.
      Imaging was repeated after a median of 13 months. RESULTS: Visual analysis of
      repeat FDG PET revealed similar abnormalities in 10 of 11 children.
      Semiquantitative analysis revealed similar sited abnormalities in eight children.
      One child with ictal hypermetabolism initially had an inconsistent second scan.
      Magnetic resonance spectra in three children showed the N-acetyl
      aspartate/choline ratio was lower in the hypometabolic focus than in the
      reciprocal area on the opposite side, in two children it was higher, and in one
      child it was equal. Surface rendered MRI was normal in seven of eight children,
      and showed temporal lobe asymmetry in one. CONCLUSION: In children with
      established epileptic encephalopathies most hypometabolic areas on FDG PET are
      stable over time. While focal neuronal loss is likely in these areas in some
      children, microdysplasias or other focal cortical dysplasias are probable in
      others.

PMID- 9771251
TI  - Metabolic handling of 13C labelled tripalmitin in healthy controls and patients
      with cystic fibrosis.
AB  - AIM: To examine the gastrointestinal handling and metabolic disposal of
      emulsified [1-13C]palmitic acid esterified into a triglyceride in nine healthy
      children and seven patients with cystic fibrosis on enzyme replacement treatment.
      METHODS: After an overnight fast, each child was given 10 mg/kg body weight
      [1,1,1-13C]tripalmitin with a standardised test meal of low natural 13C
      abundance. The total enrichment of 13C was measured using isotope ratio mass
      spectrometry in stool collected for a period of up to five days and in breath
      samples collected over a 24 hour period. RESULTS: The mean proportion of
      administered 13C label excreted in stool was 6% (range, 1-12.7%) in healthy
      children and 24.6% (range, 0-64%) in patients with cystic fibrosis. Healthy
      children excreted 31.3% of the administered label on their breath (range, 14.2
      42.9%). Correcting the excretion of administered 13C label on the breath for
      differences in digestion and absorption in patients with cystic fibrosis
      increased the difference between individuals from 0-31.3% of administered dose
      (mean, 17.9%) to 0-49.1% of absorbed dose (mean, 23.2%) and was poorly related to
      the amount of 13C label in stool. CONCLUSION: Measurements of breath 13CO2 do not
      consistently reflect the gastrointestinal handling of emulsified 13C labelled
      tripalmitin because of differences in digestion and absorption in cystic
      fibrosis. Further studies need to examine whether "breath tests" alone can
      predict with confidence the gastrointestinal handling of other 13C labelled
      triglycerides and fatty acids.

PMID- 9771252
TI  - Immunoglobulin replacement treatment by rapid subcutaneous infusion.
AB  - Long term intravenous immunoglobulin (IVIG) infusion is an effective treatment
      for children with immunodeficiencies, but can be complicated by poor venous
      access, systemic adverse reactions, and the need for frequent hospital admission.
      Rapid subcutaneous immunoglobulin (SCIG) infusion has been found to be effective
      in adults with primary immunodeficiency. Twenty six children were treated with
      SCIG for a median period of two years (range six months to 3.5 years). Fifteen
      children had previously been treated with IVIG. Retrospective analysis showed
      that trough IgG concentrations while receiving SCIG were comparable with those
      while receiving IVIG during maintenance treatment. In severe
      hypogammaglobulinaemia, however, initial loading with SCIG or IVIG is probably
      indicated. During the treatment period there was no systemic adverse reaction nor
      severe reaction requiring admission to hospital. The subjective impression of all
      families was a significant improvement in the quality of life. This preliminary
      experience with SCIG in children suggests that it is an effective, convenient,
      and well tolerated alternative to intravenous treatment. Larger prospective
      studies are required to determine the place of SCIG in the management of
      immunodeficiencies.

PMID- 9771253
TI  - X linked lymphoproliferative disease in a United Kingdom family.
AB  - X linked lymphoproliferative disease (XLP; Duncan's disease) is a rare disorder
      affecting boys and characterised by a defective immune response to Epstein-Barr
      virus caused by a mutation in a gene located at chromosome Xq25. Three siblings
      with XLP in a single UK family are reported and the variation in phenotypic
      expression of the disease in these siblings described. One of the siblings with
      life threatening fulminant infectious mononucleosis was successfully treated by
      chemotherapy, followed by bone marrow transplantation using an unaffected brother
      as the donor. A healthy baby boy recently born into the family was identified as
      carrying the defective maternal X chromosome using molecular genetic linkage
      analysis. This family illustrates the extent of present understanding of this
      often fatal condition.

PMID- 9771254
TI  - Errors by paediatric residents in calculating drug doses.
AB  - BACKGROUND: Errors in calculating drug doses in infants and small children can
      cause morbidity and mortality, especially with agents exhibiting a narrow
      therapeutic window. A previous study from this institution has detected potential
      life threatening errors in calculations performed by trainees while writing
      prescriptions. OBJECTIVES: To verify whether the true incidence of trainees'
      errors in prescribing can be explained by impaired calculation skills in written
      tests. SETTING: A tertiary paediatric hospital; educational rounds for core
      paediatric residents. METHODS: Two anonymous written tests, which included
      calculations of doses similar to those performed at the paediatric bedside; one
      was conducted in 1993 and one in 1995. RESULTS: Thirty four paediatric residents
      participated in 1993 and 30 in 1995. A substantial number of trainees in both
      years committed at least one error. In general, there was no correlation between
      the length of training (0 to 4 years) and likelihood of making a mistake. Three
      trainees in 1993 and four in 1995 committed 10-fold errors. These seven residents
      committed significantly more errors than the rest of the group in each of the
      tests separately. All seven were in their first two years of training, and six
      were in their first year of residency. CONCLUSIONS: A substantial proportion of
      paediatric trainees make mistakes while calculating drug doses under optimal test
      conditions. Some trainees commit 10-fold errors, which may be life threatening.
      The results of these anonymous tests suggest that testing of calculations skills
      should be mandatory, and appropriate remedial steps should follow to prevent
      paediatric patients receiving wrong drug dosages.

PMID- 9771255
TI  - Accuracy and reproducibility of low dose insulin administration using pen
      injectors and syringes.
AB  - Many children with diabetes require small doses of insulin administered with
      syringes or pen-injector devices (at the Booth Hall Paediatric Diabetic Clinic,
      20% of children aged 0-5 years receive 1-2 U insulin doses). To determine how
      accurately and reproducibly small doses are delivered, 1, 2, 5, and 10 U doses of
      soluble insulin (100 U/ml) were dispensed in random order 15 times from five new
      NovoPens (1.5 ml), five BD-Pens (1.5 ml), and by five nurses using 30 U syringes.
      Each dose was weighed, and intended and actual doses compared. The two pen
      injectors delivered less insulin than syringes, differences being inversely
      proportional to dose. For 1 U (mean (SD)): 0.89 (0.04) U (NovoPen), 0.92 (0.03) U
      (BD-Pen), 1.23 (0.09) U (syringe); and for 10 U: 9.8 (0.1) U (NovoPen), 9.9 (0.1)
      U (BD-Pen), 10.1 (0.1) U (syringe). The accuracy (percentage errors) of the pen
      injectors was similar and more accurate than syringes delivering 1, 2, and 5 U of
      insulin. Errors for 1 U: 11(4)% (NovoPen), 8(3)% (BD-Pen), 23(9)% (syringe). The
      reproducibility (coefficient of variation) of actual doses was similar (< 7%) for
      all three devices, which were equally consistent at underdosing (pen-injectors)
      or overdosing (syringes) insulin. All three devices, especially syringes, are
      unacceptably inaccurate when delivering 1 U doses of insulin. Patients on low
      doses need to be educated that their dose may alter when they transfer from one
      device to another.

PMID- 9771256
TI  - Melatonin treatment in an institutionalised child with psychomotor retardation
      and an irregular sleep-wake pattern.
AB  - An institutionalised 13 year old girl with psychomotor retardation suffered from
      an irregular sleep-wake pattern. Multiple measurements of urinary sulphatoxy
      melatonin (aMT6) concentrations were abnormally low, without any significant day
      night differences. Administration of exogenous melatonin (3 mg) at 18:00 resulted
      in increased nocturnal urinary aMT6 concentrations and improvements in her sleep
      wake pattern. Melatonin may help disabled children suffering from sleep
      disorders.

PMID- 9771257
TI  - Where should paediatric surgery be performed?
AB  - We have tried to review the evidence for the organisation of paediatric surgical
      care. Difficulties arise because of the lack of published data from district
      general hospitals concerning paediatric surgical conditions. Hence much of the
      debate about the surgical management of children is based on anecdotal evidence.
      However, at a time when the provision of health care is being radically
      reorganised to an internal market based on a system of purchasers and providers
      it is more important than ever to understand the issues at stake. Two separate
      issues have been discussed: the role of the specialist paediatric centre and the
      provision of non-specialist paediatric surgery in district general hospitals.
      There are arguments for and against large regional specialist paediatric centres.
      The benefits of centralisation include concentration of expertise, more
      appropriate consultant on call commitment, development of support services, and
      junior doctor training. The disadvantages include children and their families
      having to travel long distances for care, and the loss of expertise at a local
      level. If specialist paediatric emergency transport is available the benefits of
      centralisation far outweigh the adverse effects of having to take children to a
      regional paediatric intensive care centre. Specialist paediatric centres are
      aware of the importance of treating children and their parents as a family unit
      as highlighted by the Platt committee; this is an important challenge and
      enormous improvements have occurred to provide proper accommodation for families
      while their children are treated in hospital. To keep these arguments of large
      distances and separation from the home in context, one paediatric intensive care
      unit in Victoria, Australia, providing a centralised service to a region larger
      in are than England and with a similar admission rate, has a lower mortality rate
      than the decentralised paediatric intensive care provided in the Trent region of
      the UK. There is clear evidence that all neonatal surgery and anaesthesia should
      be conducted only by specialists. The debate now centres around the number of
      complex surgical cases a unit should treat to maintain its specialist status. The
      NHS executive, in its guidelines on contracting for specialist services,
      emphasises that "Sensible contracting needs to take into account the optimum
      population size not only for the stability of contracted referrals but also to
      give sufficient 'critical mass' for clinical effectiveness." Achieving this
      balance has consequences, not just for the maintenance of surgical expertise, but
      for the essential ancilliary services. There is clear evidence in anaesthesia
      that anaesthetists doing small numbers of neonatal procedures had significantly
      worse results. The same seems to be true in the fields of oncology, radiology,
      pathology, and intensive care. The reasons why the results of management of
      certain paediatric conditions are better at specialist centres are open to
      speculation. Presumably greater exposure to rare complex cases, concentration of
      expertise, more peer review, and a trickle down effect of the multidisciplinary
      approach all help to keep health care workers up to date with current world
      practice. In addition, it allows for appropriate specialist on call rotas and
      dedicated junior staff. If insufficient numbers of specialist surgical cases are
      being treated at a centre then the whole multidisciplinary team suffers. The 1989
      NCEPOD report states "that paediatricians and general surgeons must recognise
      that small babies differ from other patients not only in size, and that they pose
      quite separate problems of pathology and management." The need for large centres
      of paediatric surgical expertise is now accepted by the Royal College of Surgeons
      of England, the British Association of Paediatric Surgeons, the Senate of Surgery
      of Great Britain and Ireland, the Royal College of Paediatrics and Child Health,
      the Royal College of Anaesthetists, the Audit

PMID- 9771258
TI  - Status epilepticus: pathophysiology, epidemiology, and outcomes.

PMID- 9771259
TI  - Emergency treatment of acute seizures and status epilepticus.

PMID- 9771261
TI  - Intensive interventions to improve parenting.

PMID- 9771260
TI  - Diabetes insipidus.

PMID- 9771262
TI  - A case of X linked agammaglobulinaemia complicated with systemic amyloidosis.

PMID- 9771263
TI  - Turner's syndrome, anorexia nervosa, and anabolic steroids.

PMID- 9771265
TI  - Recent advances in opioid pharmacology.

PMID- 9771264
TI  - The role of negative pressure ventilation.

PMID- 9771266
TI  - Novel routes of opioid administration.

PMID- 9771267
TI  - Peripheral and central mechanisms of pain.

PMID- 9771268
TI  - Molecular mechanisms of opioid receptor signal transduction.

PMID- 9771269
TI  - Stimulatory effects of opioids.

PMID- 9771271
TI  - Recent advances and developments in the clinical use of i.v. opioids during the
      peroperative period.

PMID- 9771270
TI  - The orphanin FQ system: an emerging target for the management of pain?

PMID- 9771272
TI  - Remifentanil and tramadol.
AB  - The lack of analgesic efficacy limits tramadol as a sole agent to treat severe
      pain after surgery. However, it has a relative lack of respiratory depressant and
      constipating effects compared with morphine and codeine, and does not share the
      propensity of nonsteroidal anti-inflammatory drugs to provoke asthma,
      gastrointestinal mucosal damage and renal impairment. It may well have a place in
      the management of pain after surgery, in combination with another drug, such as
      paracetamol, or after control of the worst of pain after surgery by a regional
      local anaesthetic technique.

PMID- 9771273
TI  - Opioid tolerance: the clinical perspective.

PMID- 9771274
TI  - Epibatidine and pain.

PMID- 9771275
TI  - Pharmacology and potential therapeutic uses of cannabis.

PMID- 9771276
TI  - Adverse effects of extradural and intrathecal opiates: report of a nationwide
      survey in Sweden. 1982.

PMID- 9771277
TI  - Hazards of carbon dioxide insufflation during thoracoscopy.

PMID- 9771278
TI  - Midazolam given as an intranasal spray in children.

PMID- 9771280
TI  - Submandibular duct stone and difficult tracheal intubation.

PMID- 9771279
TI  - The CardioPump: CEPOD guidelines and validation of new techniques.

PMID- 9771281
TI  - Treatment of postoperative nausea and vomiting by acupressure.

PMID- 9771282
TI  - Local analgesia in early and late stages of labour.

PMID- 9771283
TI  - A guide for tube exchange using a fibrescope and the plastic sheath of a
      guidewire in small children.

PMID- 9771284
TI  - Sevoflurane for difficult tracheal intubation.

PMID- 9771285
TI  - Sevoflurane for difficult tracheal intubation.

PMID- 9771286
TI  - Sevoflurane for difficult tracheal intubation.

PMID- 9771287
TI  - Early vs late tracheal extubation after CABG surgery.

PMID- 9771288
TI  - Venous air embolism and PEEP: a clinical research blind-spot.

PMID- 9771289
TI  - Walking extradurals.

PMID- 9771290
TI  - Change of nasogastric tube via Seldinger technique.

PMID- 9771291
TI  - Observation and purpose: are ventilatory periodicities fine tuning or accidents
      of physiology?

PMID- 9771292
TI  - New considerations in pharmacokinetic variability: within-patient variability
      over time.

PMID- 9771293
TI  - Accidental i.v. injection of local anaesthetics: an avoidable event?

PMID- 9771294
TI  - Could do better: statistics in anaesthesia research.

PMID- 9771295
TI  - Do the pharmacokinetics of vecuronium change during prolonged administration in
      critically ill patients?
AB  - Neuromuscular blocking drugs may be administered over several days to patients in
      the intensive care unit (ICU), but their pharmacokinetics have been studied at
      only one point in time, or assumed to be constant throughout the period of
      administration. We sought to determine if, in individual patients, the
      pharmacokinetics of vecuronium changed over the course of its administration in
      the ICU. In six critically ill patients, we measured plasma vecuronium
      concentrations during two periods: first, during initial administration of
      vecuronium and second, after its administration continuously for 3-6 days. A
      pharmacokinetic model was fitted to these plasma concentration data, and its
      parameters permitted to vary between the periods to determine if they had
      altered. Individual clearance values during the study ranged from 1.4 to 4.4 ml
      kg-1 min-1. During prolonged administration, vecuronium clearance increased in
      three and decreased in two patients. This change ranged from a 61% decrease to a
      58% increase, and was not linked to any clinical factor. The steady-state volume
      of distribution (range 368-1765 ml kg-1; median 494 ml kg-1) did not change in
      any patient during the study. The change in clearance of vecuronium during its
      prolonged administration in critically ill patients suggests that future studies
      of neuromuscular blocking drugs in the ICU should take account of their changing
      pharmacokinetics over the course of administration.

PMID- 9771296
TI  - Dose-response curve and time-course of effect of vecuronium in male and female
      patients.
AB  - To determine the differences between men and women in the dose-response curve and
      the time-course of effect of vecuronium, we studied 60 adult patients (30 male
      and 30 female), ASA I, age 18-51 yr, undergoing elective plastic surgery.
      Anaesthesia was maintained with nitrous oxide 60% in oxygen; thiopentone and
      incremental doses of fentanyl were given as required. Neuromuscular function was
      assessed mechanomyographically using the train-of-four (TOF) stimulation at the
      wrist every 12 s. The percentage depression of T1 was used as the study variable.
      The dose-response relationship of vecuronium was determined by a cumulative dose
      response technique. The dose-response curve in men was shifted in a parallel
      fashion to the right, indicating a decrease in the sensitivity to vecuronium
      induced neuromuscular block, compared with women. The ED50, ED90 and ED95 of
      vecuronium were 23.9 (4.7), 45.4 (11.2) and 55.7 (14.3) micrograms kg-1 in men
      and 18.4 (3.7), 33.5 (7.8) and 39.8 (9.6) micrograms kg-1 in women respectively.
      There were statistically significant differences in these values between the two
      groups (P < 0.01 in each instance). After a total dose of vecuronium 80
      micrograms kg-1, neuromuscular block was significantly longer in women than in
      men. The duration of peak effect, clinical duration, and the total duration were
      18.7 (7.1), 26.6 (8.8) and 50.6 (16.0) min respectively in men and 26.0 (7.2),
      37.1 (11.2) and 65.9 (20.7) min in women. They differed significantly between men
      and women (P < 0.005 in each case).

PMID- 9771297
TI  - Quantitative electroencephalographic analysis of the biphasic concentration
      effect relationship of propofol in surgical patients during extradural analgesia.
AB  - We studied effects on the EEG of propofol infused at a rate of 0.5 mg kg-1 min-1
      for 10 min in 10 healthy male surgical patients under extradural analgesia. The
      EEG amplitude in six frequency bands was related to arterial blood propofol
      concentrations and responsiveness to verbal commands. The EEG amplitude showed a
      characteristic biphasic response to increasing blood propofol concentrations in
      all frequency bands. During the infusion, patients lost responsiveness when EEG
      amplitudes in the high frequency bands were decreasing after having reached a
      maximum. EEG changes were different during infusion and emergence.
      Pharmacodynamic modelling, using two effect compartments with dissimilar
      equilibration constants, resulted in satisfactory fits. We conclude that propofol
      exerts a biphasic effect on the EEG amplitude in all frequency bands. The
      dissimilarity of EEG changes during infusion and during emergence suggests that
      two effect compartments with different equilibration constants exert opposing
      effects on the EEG.

PMID- 9771298
TI  - Effects of premedication on dose requirements for propofol: comparison of
      clonidine and hydroxyzine.
AB  - The influence of a single dose of clonidine (5 micrograms kg-1) or hydroxyzine (1
      mg kg-1) on intraoperative propofol requirements was determined in 28 male
      patients (ASA I) undergoing elective orthopaedic surgery. Patients were randomly
      allocated to receive either clonidine or hydroxyzine orally 2 h before induction
      of anaesthesia. After a loading dose of propofol (2.5 mg kg-1), mivacurium (0.2
      mg kg-1) and alfentanil (15 micrograms kg-1), anaesthesia was maintained with a
      standardized propofol infusion supplemented with nitrous oxide (66%) in oxygen.
      During surgery, additional propofol boluses (1 mg kg-1) were administered when
      heart rate or mean arterial pressure increased by more than 10% compared with
      preinduction values. The clonidine group demonstrated a 14.5% decrease in total
      propofol requirements (P < 0.05) and a 52.2% reduction in additional propofol
      boluses (P < 0.02) in comparison with the hydroxyzine group. intraoperative heart
      rate and mean arterial pressure were significantly lower in the clonidine group
      but no patients needed treatment with ephedrine for hypotension or bradycardia.
      Recovery of psychomotor function and discharge from the recovery room were not
      delayed in the clonidine group. This study indicates that 5 micrograms kg-1
      clonidine given as premedication in ASA I patients reduces intraoperative
      propofol requirements in comparison with 1 mg kg-1 hydroxyzine without inducing
      adverse effects on recovery or haemodynamic stability.

PMID- 9771299
TI  - Administration of a crystalloid fluid preload does not prevent the decrease in
      arterial blood pressure after induction of anaesthesia with propofol and
      fentanyl.
AB  - Anaesthesia was induced in 58 women (ASA I or II) undergoing elective
      gynaecological procedures, using propofol 2.5 mg kg-1 and fentanyl 1.5 micrograms
      kg-1. Patients were allocated to receive 20 ml kg-1 of crystalloid fluid preload
      over 20 min or to receive no fluids before induction of anaesthesia. A
      significant decrease in systolic arterial pressure (< 75% of baseline value)
      occurred in both the fluid-loaded and the control groups, and was similar in both
      groups. Administration of a fluid preload did not attenuate the decrease in
      systolic arterial pressure after induction of anaesthesia with propofol and
      fentanyl.

PMID- 9771300
TI  - Postoperative hypoxaemia: continuous extradural infusion of bupivacaine and
      morphine vs patient-controlled analgesia with intravenous morphine.
AB  - We carried out a randomized prospective study in 60 patients who had undergone
      major abdominal surgery for cancer. For postoperative pain control, 30 patients
      received continuous extradural infusion of 0.125% bupivacaine 12.5 mg h-1 and
      morphine 0.25 mg h-1 (EXI group) and 30 received patient-controlled analgesia
      (PCA) with intravenous morphine (1 mg bolus, 5-min lock-out and maximum dose 20
      mg 4h-1). Both groups had general anaesthesia. The two groups were compared for
      postoperative pain scores, satisfaction, sedation and oxygen saturation. Oxygen
      saturation was recorded continuously the night before surgery and for two
      consecutive postoperative nights. Episodes of moderate desaturation (90% > SpO2
      85%) were more frequent in the EXI group than in the PCA group (P < 0.05). Pain
      scores were lower in the EXI group compared with the PCA group at rest and while
      coughing (P < 0.05). No significant difference was found for patient sedation and
      satisfaction.

PMID- 9771301
TI  - Patient-maintained analgesia with target-controlled alfentanil infusion after
      cardiac surgery: a comparison with morphine PCA.
AB  - The performance of a patient-demand, target-controlled alfentanil infusion system
      was compared with that of a traditional morphine patient-controlled analgesia
      (PCA) pump in 120 adult patients after cardiac surgery. Patients were randomized
      to one of the two PCA systems for their postoperative analgesia in the intensive
      care unit and pain, nausea and sedation scores were recorded every 4 h for the
      first 24 h. Episodes of hypoxaemia, myocardial ischaemia and haemodynamic
      instability were also recorded. In patients using the alfentanil system the
      overall median visual analogue pain score was 2.3 (95% Cl 2.3-2.8) compared with
      3.0 (95% Cl 2.7-3.2) in those using morphine PCA (P < 0.05), but both systems
      delivered high-quality analgesia. The two groups did not differ with respect to
      the overall sedation scores, the frequency of postoperative nausea and vomiting,
      haemodynamic instability, myocardial ischaemia or hypoxaemia.

PMID- 9771302
TI  - Comparison of remifentanil in combination with isoflurane or propofol for short
      stay surgical procedures.
AB  - There are few data in the literature that describe the use of remifentanil when
      administered as a component of an inhalation or total i.v. anaesthetic (TIVA)
      technique. We studied 251 male and female patients, aged 18-75 years, ASA I-II,
      undergoing inguinal hernia repair, arthroscopic knee surgery or varicose vein
      surgery of at least 30 min duration without premedication. Patients were
      randomized to receive a remifentanil loading dose of 1.0 microgram kg-1 followed
      by a continuous infusion of 0.5 microgram kg-1 min-1 in combination with
      isoflurane (end-tidal concentration 0.6%), (Group I, n = 115) or propofol
      (initial infusion rate 9 mg kg-1 h-1 reduced to 6 mg kg-1 h-1 after 10 min),
      (Group P, n = 118). The remifentanil infusion rate was reduced by 50%, 5 min
      after tracheal intubation. Intraoperative stresses were treated with a
      remifentanil bolus (1 microgram kg-1) followed by an increase in the remifentanil
      infusion rate. At the insertion of the last suture, the remifentanil infusion and
      concomitant anaesthetic were switched off simultaneously. Times to spontaneous
      respiration, adequate respiration and tracheal extubation were significantly
      shorter in group I compared with group P (6.4 min vs 7.6 min, P < 0.01; 7.6 min
      vs 9.3, P < 0.003; 7.8 min vs 9.5 min, P < 0.015). Overall mean systolic blood
      pressures during surgery were greater in group P compared with group I (P < 0.05)
      but the absolute differences were clinically insignificant (4-5 mm Hg).

PMID- 9771303
TI  - Effect of pre-treatment with intravenous atropine or glycopyrrolate on cardiac
      arrhythmias during halothane anaesthesia for adenoidectomy in children.
AB  - We studied the effect of anticholinergics on the incidence of cardiac arrhythmias
      during paediatric anaesthesia. ASA I-II children (n = 77) undergoing
      adenoidectomy were randomly allocated to three groups. Intravenous atropine 0.02
      mg kg-1 was given in group A (n = 25), glycopyrrolate 0.004 mg kg-1 in group G (n
      = 27) and physiological saline in group P (n = 25) 3 min before the induction of
      anaesthesia. The children breathed spontaneously under halothane anaesthesia with
      66% nitrous oxide in oxygen after induction with thiopentone and succinylcholine.
      Perioperative monitoring of the ECG (Holter recordings) and oxygen saturation was
      carried out. Ventricular tachycardia occurred in 16.0%, 18.5% and 12.0% of the
      children in groups A, G and P respectively (ns). The incidence of ventricular
      arrhythmias (ventricular tachycardia, ventricular bigeminy, ventricular premature
      beats > 10) was 20.0% in group A, 44.4% in group G and 36.0% in group P (ns).
      Bradycardia (< 70 beats min-1) was observed in 0.0%, 14.8% and 24.0% of patients
      in groups A, G and P respectively (A vs P, P < 0.05). The use of anticholinergics
      did not influence the incidence of ventricular arrhythmias during halothane
      anaesthesia in children. Bradycardia was more common in the placebo group than in
      the atropine group.

PMID- 9771304
TI  - Tropisetron reduces vomiting after tonsillectomy in children.
AB  - Nausea and vomiting are common after adenotonsillectomy. Tropisetron is a new,
      long-acting serotonin antagonist that is an effective antiemetic in adults. Its
      effect on postoperative nausea and vomiting in children is unknown. We carried
      out a randomized, double-blind study of the effects of a single i.v. dose of
      tropisetron on vomiting after tonsillectomy with or without adenoidectomy in
      children. Forty-eight children undergoing tonsillectomy or adenotonsillectomy
      received at induction of anaesthesia either tropisetron 0.1 mg kg-1 or placebo.
      The incidence of vomiting was recorded for the first 24 h after surgery by
      nursing staff and then by parents after discharge from hospital. Children
      received metoclopramide 0.15 mg kg-1 as a rescue antiemetic. We found that
      tropisetron reduced the overall incidence of emetic episodes after surgery (29%
      compared with 65% in control group; P = 0.019) and the incidence of severe
      vomiting (0% compared with 52% in control group; P < 0.001). We conclude that
      tropisetron is an effective antiemetic for children undergoing tonsillectomy.

PMID- 9771305
TI  - Granisetron in the prevention of nausea and vomiting after middle-ear surgery: a
      dose-ranging study.
AB  - This study was undertaken to determine the minimum effective dose of granisetron,
      a selective 5-hydroxytryptamine type 3 receptor antagonist, for the prevention of
      postoperative nausea and vomiting (PONV) after middle-ear surgery. In a
      randomized, double-blind, placebo-controlled trial, 120 women (ASA I) received
      placebo (saline) or granisetron at three different doses (20 micrograms kg-1, 40
      micrograms kg-1, 100 micrograms kg-1) i.v. immediately before the induction of
      anaesthesia (n = 30 for each group). A standard general anaesthetic technique was
      used throughout. A complete response, defined as no PONV and no need for another
      rescue antiemetic during 0-3 h after anaesthesia, occurred in 40%, 43%, 83% and
      87% of patients who had received placebo, granisetron 20 micrograms kg-1,
      granisetron 40 micrograms kg-1 or granisetron 100 micrograms kg-1, respectively;
      the corresponding incidence during 3-21 h after anaesthesia was 47%, 47%, 87% and
      87% (P < 0.05; overall Fisher's exact probability test). Granisetron 40
      micrograms kg-1 appears to be the minimum effective dose for preventing PONV in
      women undergoing middle-ear surgery.

PMID- 9771306
TI  - Respiratory complications associated with tracheal intubation and extubation.
AB  - We conducted a prospective survey on the incidence of respiratory complications
      associated with tracheal intubation and extubation in 1005 patients who underwent
      elective general anaesthesia over a 4-month period. During induction of
      anaesthesia, respiratory complications occurred in 46 patients (4.6%; 95%
      confidence limits (CL): 3.3, 5.9%). The common complications were coughing (1.5%)
      and difficult ventilation through a facemask (1.4%). Tracheal intubation was
      difficult in eight patients (0.8%). Complications occurred immediately after
      tracheal extubation in 127 patients (12.6%; 95% CL: 10.6, 14.7) and in the
      recovery room in 95 patients (9.5%; 95% CL: 7.6, 11.3%). The common complications
      immediately after extubation were coughing (6.6%) and oxygen desaturation (SaO2 <
      90%) (2.4%), and in the recovery room, airway obstruction (3.8%) and coughing
      (3.1%). The incidence of complications was significantly higher immediately after
      tracheal extubation than during induction of anaesthesia (P << 0.001). Even when
      all incidents of coughing that occurred after tracheal extubation were
      disregarded as a complication, the overall incidence was still higher immediately
      after extubation (7.4%) than during induction of anaesthesia (P < 0.01). We
      conclude that the incidence of respiratory complications associated with tracheal
      extubation may be higher than that during tracheal intubation.

PMID- 9771307
TI  - Hospital mortality after urgent and emergency laparotomy in patients aged 65 yr
      and over. Risk and prediction of risk using multiple logistic regression
      analysis.
AB  - We studied 107 patients aged over 65 years undergoing urgent or emergency
      laparotomy. Aspects of preoperative assessment, perioperative management and
      postoperative care were analysed by multiple logistic regression to determine the
      factors that predicted hospital survival. We determined which factors influenced
      anaesthetists' prediction that patients would survive. These predictions were
      made both before and immediately after operation. The factors associated with the
      use of invasive cardiovascular monitoring were also studied. We obtained a model
      that accounted for 93% of the variability in the likelihood of survival. Age and
      ASA status were significant predictors of survival (P < 0.05), and of
      anaesthetists' prediction of mortality both before and after operation. Several
      other factors were significant determinants of survival but were not determinants
      of the anaesthetist's opinion regarding survival.

PMID- 9771308
TI  - Hepatic energy metabolism during ketamine and isoflurane anaesthesia in
      haemorrhagic shock.
AB  - The effects of ketamine and isoflurane on the phosphoenergetic state of the liver
      during haemorrhage were investigated using 31P nuclear magnetic resonance (NMR)
      spectroscopy. Male Wistar rats were anaesthetized with ketamine (1.0 mg kg-1 min
      1 i.v., Ket 1.0 group, or 1.5 mg kg-1 min-1 i.v., Ket 1.5 group), or isoflurane
      1.4% (Iso group). Haemorrhage was induced by withdrawing blood until the mean
      arterial pressure was reduced to 40 mm Hg, and this pressure level was then
      maintained for 45 min. Hepatic energy metabolism was evaluated from the changes
      in adenosine triphosphate (ATP) and inorganic phosphate (Pi). The beta-ATP
      decrease and the Pi increase were more marked in the two Ket groups than in the
      Iso group. At 20 min after haemorrhage, the beta-ATP peak areas were 34%, 32% and
      76%, and the Pi peak areas were 257%, 260% and 160% of their initial values in
      the Ket 1.0, Ket 1.5 and Iso groups, respectively. NMR data were supported by
      chemical assessments. These results demonstrated that, in terms of
      phosphoenergetic levels, a continuous administration of 1.0 or 1.5 mg kg-1 min-1
      ketamine markedly decreased hepatic metabolism during haemorrhagic shock, whereas
      inhalation of 1.4% isoflurane mitigates the metabolic damage.

PMID- 9771309
TI  - Possible involvement of multiple human cytochrome P450 isoforms in the liver
      metabolism of propofol.
AB  - Previous studies of propofol (2,6-diisopropylphenol) pharmacology have shown that
      this widely used anaesthetic drug is extensively cleared from the body by
      conjugation of the parent molecule or its quinol metabolite. On the basis of
      potential influence of propofol on the metabolism of co-administered agents, many
      investigators have evaluated the effects of propofol on cytochrome P450 (CYP)
      activities. CYP isoforms involved in propofol metabolism are not defined. In this
      study, our objective was to elucidate further the CYP isoforms responsible for
      the hydroxylation of propofol. Using microsomes from 12 different human livers,
      we investigated CYP isoforms involved in propofol hydroxylase activity, using
      selective chemical inhibitors of CYP isoforms, correlation with immunoquantified
      specific CYP isoform content, immunoinhibition, and 11 functionally active human
      CYP isoforms expressed in a heterologous system (yeast and human B-lymphoblastoid
      cells). We found a low variability in the production of the hydroxylated
      metabolite of propofol, 2,6-diisopropyl-1,4-quinol. This activity was mediated by
      CYP and followed Michaelis-Menten kinetics with apparent K(M) and Vmax values of
      18 microM (95% Cl 15.1-20.1) and 2.6 nmol min-1 mg-1 (95% Cl 2.45-2.68)
      respectively. Part of the propofol hydroxylase activity was mediated by CYP2C9 in
      human liver, especially at low substrate concentration. Moreover, propofol was
      likely to be metabolized by additional isoforms such as CYP2A6, 2C8, 2C18, 2C19
      and 1A2, especially when substrate concentrations are high. This low specificity
      among CYP isoforms may contribute to the low interindividual variability (two
      fold) and may contribute to the low level of metabolic drug interactions observed
      with propofol.

PMID- 9771310
TI  - Evaluation of a new design of tracheal tube cuff to prevent leakage of fluid to
      the lungs.
AB  - A new design of tracheal tube cuff was compared with two types of high-volume,
      low-pressure (HVLP) cuffed tracheal tube for leakage of fluid from the subglottic
      space into the trachea. Spontaneous and positive-pressure ventilation were
      simulated using a mechanical lung, an intubated model trachea and a ventilator.
      Excised human tracheas were intubated and leakage past the cuff assessed.
      Distention of the tracheal wall was measured. HVLP cuffs leaked rapidly in the
      model during all modes of ventilation, and also in the excised human tracheas.
      This leakage occurred preferentially down longitudinal folds that occur in the
      HVLP cuff wall. The new design completely prevented leakage in the model during
      all modes of ventilation, during tracheal suctioning, and with tube movement. The
      new cuff also prevented leakage in the excised human tracheas. Tracheal wall
      distention and tracheal wall pressures were similar for all cuffs tested.

PMID- 9771311
TI  - Synergistic antinociceptive interaction between sevoflurane and intrathecal
      fentanyl in dogs.
AB  - This study determined the nature of the antinociceptive interaction between
      sevoflurane and intrathecal fentanyl on somatosympathetic reflexes in
      anaesthetized dogs. Afferent A delta- and C-fibre-mediated somatosympathetic
      reflexes, evoked by supramaximal electrical stimulation of tibial nerves, were
      recorded from renal sympathetic nerves. The effect of fentanyl alone,
      administered intrathecally (i.t.) in incremental doses from 2 to 64 micrograms,
      was compared with the effect of the same doses during the administration of 1.5%
      sevoflurane. The mean ED50s for the depressant effect of fentanyl (i.t.) on A
      delta and C reflexes were 35.6 micrograms and 14.2 micrograms while 1.5%
      sevoflurane, when administered alone, depressed them by 15.5% (P < 0.05) and
      27.5% (P < 0.01) respectively. During the administration of 1.5% sevoflurane, the
      mean ED50s of fentanyl (i.t.) for the depression of A delta and C reflexes were
      reduced by 76% and 75%, to 8.5 micrograms and 3.5 micrograms respectively. The
      combined antinociceptive effects of sevoflurane and intrathecal fentanyl were not
      additive but exhibited a high degree of synergistic interaction.

PMID- 9771312
TI  - Inhalation anaesthetics produce asynchronous reversal of ventilation
      inhomogeneity and increased lung resistance in a canine model of bronchial
      asthma.
AB  - Bronchial asthma is characterized by not only an increase in lung resistance but
      also inhomogeneous ventilation. We aimed to investigate how two inhalation
      anaesthetics, isoflurane and sevoflurane, relieve ventilation inhomogeneity and
      reduce lung resistance in the bronchoconstricted lung. We provoked
      bronchoconstriction in dogs by a continuous i.v. infusion of methacholine, then
      administered either isoflurane or sevoflurane. Ventilation inhomogeneity was
      quantified by the difference in respiratory phases between the regional alveolar
      pressures measured at two distinct lobes. We constructed a mathematical model
      that simulated our experimental results. Both anaesthetics decreased lung
      resistance (P < 0.01). Isoflurane significantly reduced the indices of
      inhomogeneity (P < 0.01). Sevoflurane exerted only a tendency to reduce uneven
      ventilation. Our model simulation suggested that the anaesthetics reduced
      ventilation inhomogeneity in preference to lung resistance when the dogs suffered
      from severe bronchoconstriction.

PMID- 9771313
TI  - Effects of nalbuphine, pentazocine and U50488H on gastric emptying and
      gastrointestinal transit in the rat.
AB  - We studied the effect of mixed agonist-antagonist opioids (nalbuphine and
      pentazocine) and a kappa opioid agonist (U50488H) on gastric emptying and
      gastrointestinal transit, and their interactions with morphine in rats. In each
      group, nalbuphine (0.01-30 mg kg-1), pentazocine (1-30 mg kg-1), U50488H (1-100
      mg kg(-1)1) or saline was injected i.p. at 0 min. Another four groups of rats
      received morphine 13.4 mg kg-1 (ED75) and one of the following substances:
      saline, nalbuphine, pentazocine or U50488H. In both groups, at 30 min,
      radiolabelled saline 1 ml was infused into the stomach; at 1 h, gastric emptying
      and gastrointestinal transit were calculated by measuring the radioactivity in
      the gastrointestinal tract. Slopes for dose-response curves were determined.
      Nalbuphine significantly, but only weakly, delayed gastric emptying (P < 0.0005)
      and gastrointestinal transit (P < 0.01). Pentazocine markedly inhibited both,
      whereas U50488H did not significantly inhibit either. The slopes of the dose
      response curves for nalbuphine, but not for pentazocine, on both gastric emptying
      and gastrointestinal transit were significantly less steep than those for
      morphine. Nalbuphine significantly antagonized the inhibitory effect of morphine
      on gastric emptying (P = 0.005) and gastrointestinal transit (P = 0.02), whereas
      pentazocine and U50488H did not. Nalbuphine and pentazocine delay gastric
      emptying and gastrointestinal transit, possibly by different mechanisms.

PMID- 9771314
TI  - The anaesthetist's role in acute sickle cell crisis.

PMID- 9771315
TI  - Changes in arterial-mixed venous oxygen content difference (CaO2 - CvO2) and the
      effect on shunt calculations in critically ill patients.
AB  - Many commonly used indices of pulmonary oxygen transfer assume that CaO2 - CvO2
      is constant. We studied changes in CaO2 - CvO2 in critically ill patients to
      determine the effect on calculated shunt of assuming a fixed CaO2 - CvO2. Two
      hundred pairs of arterial and mixed venous blood gas measurements were obtained
      retrospectively from 43 patients, each providing four or five pairs from a period
      of 48 h. CaO2 - CvO2 range from 13 to 74 ml l-1. The mean within-patient sd was
      6.8 ml l-1 and the overall between-patient sd was 10.9 ml l-1. Our results show
      that assuming a fixed CaO2 - CvO2 leads to errors in quantifying pulmonary oxygen
      transfer.

PMID- 9771316
TI  - Myocardial ischaemia during tracheal extubation in patients after cardiac
      surgery: an observational study.
AB  - This study examines whether there is a temporal relationship between tracheal
      extubation and myocardial ischaemia in haemodynamically stable patients extubated
      within 6 h of cardiac surgery. Fifty-two patients were studied during three time
      periods: 1, from 2 h until 30 min before extubation (90 min); 2, from 30 min
      before until 30 min after extubation (60 min); 3, from 30 min until 2 h after
      extubation (90 min). Significant ST segment changes were defined as a reversible
      ST segment depression of 2 mm or greater or an elevation of 3 mm or greater from
      baseline, lasting for 1 min or more. Fourteen patients (26.9%) had ST segment
      changes. The ischaemic burden in periods 2 and 3 was increased compared with that
      in period 1; the mean (SD) was: period 1, 19.2 (18.8) min; period 2, 35.4 (24.9)
      min; period 3, 39.6 (24.5) min; however, the mean ST deviation (mm) did not
      change. ST segment changes were associated with an increased heart rate; they
      were not related to arterial pressure. We conclude that there is a temporal
      relationship between ST segment changes and tracheal extubation after cardiac
      surgery.

PMID- 9771317
TI  - Haemodynamic responses to extubation after cardiac surgery with and without
      continued sedation.
AB  - We studied the haemodynamic response to cessation of mechanical ventilation and
      removal of the tracheal tube in 84 patients after coronary artery bypass
      grafting. Patients were sedated on the ICU with propofol 1-3 mg kg-1 h-1, and
      randomly allocated to extubation while awake or while still sedated. Systolic and
      diastolic blood pressures and heart rate increased significantly faster in the
      awake group as mechanical ventilation was stopped; systolic blood pressure 6.1
      (3.0) vs 0.7 (1.8) mm Hg min-1, diastolic blood pressure 2.1 (1.6) vs 0.2 (0.9)
      mm Hg min-1, heart rate 2.1 (1.7) vs 0.2 (0.5) beats min-2; P < 0.01 in each
      case. Treatment was required for systolic hypertension during discontinuation of
      mechanical ventilation in 20 patients (53%) in the awake group and in three
      patients (7.5%) in the sedated group (P < 0.001). No patient in the sedated group
      had any new ischaemic ECG changes. Significant new ST segment changes did not
      occur in the sedated group but were present in five patients in the awake group
      (P = 0.013), one of whom suffered a perioperative myocardial infarction. Removal
      of the tracheal tube while patients are still sedated after coronary artery
      bypass grafting is safe, and reduces the incidences of haemodynamic disturbance
      and myocardial ischaemia during extubation.

PMID- 9771318
TI  - Intra-articular injection of ketorolac in the rat knee joint: effect on articular
      cartilage and synovium.
AB  - We have investigated the effects of intra-articular (i.a.) administration of
      ketorolac in the rat knee joint. Thirty Sprague-Dawley rats were given 0.25 ml of
      a standard preparation of ketorolac trometamol (10 mg ml-1) by injection into the
      right knee joint and 0.25 ml of 0.9% physiological saline solution by injection
      into the left knee as a control. Ten rats were killed at 24 h, 10 at 48 h and 10
      at 5 days after injection. The joints were prepared and sectioned for
      histological examination. There was significantly more inflammation in those
      knees that had received i.a. ketorolac at all times of examination, with the most
      severe changes occurring 5 days after injection. A further group of 10 rats were
      given 0.25 ml of 10% w/v ethanol in physiological saline (similar to the vehicle
      for parenteral ketorolac) injected into the knee joint, with a 0.9% saline
      control injected in the other knee. These rats were then killed at 5 days (as
      this was the time interval after which we found the maximum inflammatory response
      in the earlier phase of our study). The joints were prepared and examined
      histologically. We feel that the absence of inflammatory changes in these joints
      make it unlikely that ethanol was responsible for the inflammation produced by
      ketorolac injection.

PMID- 9771319
TI  - Halothane increases the open probability of glycine-activated channel current in
      rat central neurones.
AB  - Glycine-activated single-channel currents in rat central neurones were recorded
      using the outside-out mode of the patch-clamp technique. The unitary conductance
      of the current was 21 pS. The current evoked by 10 microM glycine had a mean
      burst duration of 47.8 (2.6) ms and open probability of 0.09 (0.016). Halothane
      (1 mM) increased the open probability to 0.19 (0.03) without changing either
      unitary conductance or burst duration. These results suggest that halothane
      increased the open probability via an increase in the affinity of the receptor
      for the agonist. Potentiation of the glycine response may reduce excitability of
      postsynaptic neurones and may contribute to general anaesthesia produced by
      volatile agents.

PMID- 9771320
TI  - Ropivacaine-induced seizure after extradural anaesthesia.
AB  - Ropivacaine is considered safer than bupivacaine, on the basis of experimental
      and human data that indicate a lower systemic toxicity. Here we report the
      occurrence of a single seizure after i.v. administration of ropivacaine 120 mg
      intended for extradural block in a patient having postpartum, tubal ligation. The
      only prodromal symptom was nervousness, and the only cardiovascular manifestation
      was sinus tachycardia. Systemic toxicity, although less than that expected with
      bupivacaine, can occur with ropivacaine.

PMID- 9771321
TI  - Co-incidental diagnosis of an extradural abscess while siting an extradural
      catheter for postoperative analgesia.
AB  - Extradural abscess is a rare but serious complication of the extradural route of
      administration of analgesic drugs. We report a case of spontaneous extradural
      abscess diagnosed during placement of an extradural catheter for analgesia after
      a negative diagnostic laparotomy. Magnetic resonance imaging is the usual
      diagnostic tool of choice. This, and subsequent surgery, confirmed the diagnosis
      suspected after drainage of pus through the Tuohy needle.

PMID- 9771322
TI  - Postoperative treatment of myocardial ischaemia by thoracic extradural local
      anaesthetic.
AB  - This case report describes an episode of postoperative myocardial ischaemia after
      total oesophagectomy that was successfully treated by extradural administration
      of local anaesthetic. Extension of sympathetic blockade in this manner resolved
      the myocardial ischaemia and haemodynamic disturbances experienced by the
      patient.

PMID- 9771323
TI  - Cushing's disease treated by trans-sphenoidal selective adenomectomy in mid
      pregnancy.
AB  - The clinical course and diagnosis of a patient with Cushing's disease complicated
      by pregnancy is described, and the anaesthetic management of trans-sphenoidal
      selective adenomectomy performed during the second trimester outlined. Problems
      included obesity, diabetes, hypertension and a suboptimal airway. Fibreoptic
      awake intubation and intravenous anaesthesia were used. Insulin requirements
      decreased substantially after surgery. Early administration of hydrocortisone
      after surgery avoided the risk of an addisonian crisis but delayed biochemical
      confirmation of a metabolic cure.

PMID- 9771324
TI  - Death associated with disseminated intravascular coagulation after hip
      replacement.
AB  - Sudden-onset disseminated intravascular coagulation (DIC) occurred 3 h after
      uneventful polymethacrylate bone cement insertion for a revision left Charnley
      hip replacement. Profuse bleeding caused a hypovolaemic state aggravating
      existing myocardial ischaemia; as a result death occurred secondary to myocardial
      infarction 6 h after operation.

PMID- 9771325
TI  - Holt-Oram syndrome.
AB  - Holt-Oram syndrome (HOS) is a rare disorder characterized by congenital anomalies
      of the upper limbs and heart. Cardiac arrhythmias are common in patients with
      HOS. We successfully managed a 24-yr-old woman with HOS who underwent
      laparoscopic ovarian cystectomy. Potential problems in the anaesthetic management
      of patients with HOS are discussed.

PMID- 9771326
TI  - Factors influencing the arterial oxygen tension during anaesthesia with
      artificial ventilation. 1965.

PMID- 9771327
TI  - Death in the dental chair--an avoidable catastrophe?

PMID- 9771328
TI  - Death in the dental chair--an avoidable catastrophe?

PMID- 9771329
TI  - Optimum technique for delivery of extradural analgesia during labour.

PMID- 9771330
TI  - Inhalation anaesthetics and the Medtronic Maxima Plus membrane oxygenator.

PMID- 9771331
TI  - A leak of concern.

PMID- 9771332
TI  - Malnutrition in hospital: the case of the stroke patient.

PMID- 9771333
TI  - Information and communication technology in nutrition and dietetic education.

PMID- 9771334
TI  - Nutritional status of hospitalized acute stroke patients.
AB  - The nutritional status of 201 hospitalized stroke patients was assessed from
      anthropometric, haematological and biochemical data in an observational
      prospective study. On admission, sixty-two (31%) stroke patients had BMI < 20,
      ninety-nine (49%) had a triceps skinfolds thickness below the 25th centile,
      twenty-five (12%) had a mid-arm circumference below the 25th centile and thirty
      eight (19%) had a serum albumin concentration below 35 g/l. Baseline nutritional
      status was worse among those who later died or remained in hospital compared with
      those discharged and most patients who remained in hospital showed marked and
      significant deterioration in all measures of nutritional status within 4 weeks of
      hospitalization. After adjusting for age, stroke severity and co-morbidity, low
      serum albumin concentrations of these patients in hospital were a strong and
      independent predictor of death following acute stroke (odds ratio 1.13 (95% CI
      1.01-1.27) for 1 g/l lower serum albumin concentration).

PMID- 9771335
TI  - Are overweight women at increased risk of obesity following pregnancy?
AB  - Longitudinal studies suggest that women who already have a high BMI are at
      greater risk of maternal obesity than their lighter counterparts. The aim of the
      present study was to investigate this possibility by examining the relationship
      between reproductive history and maternal BMI in a community of 627 women from
      South Africa with a high prevalence of obesity. Standardized questionnaires were
      used to obtain detailed sociodemographic and behavioural information, while
      maternal weight and height were both measured at the time of the interview.
      Analysis of covariance (ANCOVA) showed that maternal age (r2 0.015, P = 0.001),
      smoking status (r2 0.012, P = 0.036), and social support (r2 0.011, P = 0.006)
      were all independently associated with maternal BMI. If overweight women were at
      increased risk of maternal obesity, then the positive relationship between
      reproductive history and maternal BMI should be enhanced in this relatively obese
      community, yet the ANCOVA models showed no independent association between
      gravidity and maternal BMI after controlling for the effects of confounding
      factors. Although previous longitudinal studies have found a positive association
      between prepregnant weight and long-term weight gain, this relationship might
      arise because overweight women gain more weight over a fixed period of time than
      normal weight women, and therefore they may appear to be at greater risk of
      pregnancy-related weight gains. Overweight women are at greater risk of weight
      gain generally, but there is little unequivocal evidence to suggest that they are
      at any increased risk of maternal obesity, when compared with women of lower BMI.

PMID- 9771336
TI  - Faecal pH, bile acid and sterol concentrations in premenopausal Indian and white
      vegetarians compared with white omnivores.
AB  - Faecal bulk, pH, water content, the concentrations of neutral sterols and bile
      acids and dietary intakes were measured in twenty-two Indian vegetarian, twenty
      two white omnivorous and eighteen white vegetarian premenopausal women. Faecal
      bulk and water content were greater and pH lower in the Indian vegetarians. Total
      faecal animal sterol and coprostanol concentrations expressed on a dry-weight
      basis were lower in the vegetarians compared with the omnivores. The faecal
      sterol concentrations were correlated with dietary cholesterol intake. Primary
      bile acids were detected in six Indian vegetarians, two white vegetarians and two
      white omnivores; secondary bile acids were detected in all the white omnivores
      and vegetarian subjects but not in two of the Indian vegetarians. Total faecal
      free bile acid and conjugated bile acid concentrations were lower in the white
      vegetarians compared with the omnivores. Faecal lithocholic acid concentrations
      were lower in both Indian and white vegetarians. The lithocholic: deoxycholic
      acid ratio and coprostanol: total animal sterols ratio were significantly lower
      in the Indian vegetarians compared with the omnivores. Both ratios were
      positively correlated with faecal pH. Stepwise multiple regression analyses were
      undertaken in order to identify which nutrients influenced faecal pH, lithocholic
      and deoxycholic acid concentrations. The intakes of starch and dietary fibre were
      negatively associated with faecal concentrations of lithocholic and deoxycholic
      acid. Starch intake alone was negatively associated with faecal pH. The results
      of this study confirm that diets high in dietary fibre decrease faecal bile acid
      concentrations and suggest that the complex carbohydrates present in Indian
      vegetarian diets influence faecal pH and inhibit the degradation of faecal
      steroids.

PMID- 9771337
TI  - Calcium levels in maternal milk: relationships with calcium intake during the
      third trimester of pregnancy.
AB  - The aim of the present study was to investigate the relationship of Ca intake and
      serum Ca levels during the third trimester of pregnancy with levels of the same
      mineral in transition milk (days 13-14 of lactation) and mature milk (day 40 of
      lactation). The study subjects were a group of fifty-seven healthy, lactating
      mothers aged between 18 and 35 years (mean 27 (SD 3.7) years) whose pregnancies
      and labour were attended by the Department of Obstetrics and Gynaecology of
      Cuenca INSALUD Hospital, Spain. Ca intake during the third trimester was
      determined by recording the consumption of foods over a 5 d period and by
      registering Ca provided by dietary supplements. The same method was used to
      investigate the intake of protein, vitamin D, fibre and Fe, nutrients that could
      affect the use of dietary Ca. Ca levels in maternal serum during this stage of
      pregnancy, during lactation and in transition and mature milk samples, were
      determined using 2-cresolphthalein complexone. During pregnancy 70.2% of subjects
      showed Ca intakes below 1100 mg/d (75th percentile). The consumption of Ca
      supplements was very small and hardly modified the mean quantity supplied by the
      diet. Subjects with an intake < 1100 mg/d showed no fall in Ca levels in serum,
      either during pregnancy or lactation, nor were decreased levels found in
      transition milk. However, these subjects showed lower Ca levels in mature milk
      (5.95 (SD 1.56) mmol/l) than did subjects with greater Ca intakes (6.82 (SD 1.31)
      mmol/l). This may suggest that breast-fed babies of mothers with lower Ca intakes
      during pregnancy also receive less Ca.

PMID- 9771338
TI  - Major determinants of fasting heat production and energetic cost of activity in
      growing pigs of different body weight and breed/castration combination.
AB  - A total of sixty-five observations on heat production during fasting and physical
      activity were obtained in four groups of pigs differing in breed and/or
      castration (Meishan (MC) and Large White (LWC) castrates and Large White (LWM)
      and Pietrain (PM) males) with body weight (BW) ranging between 25 and 60 kg. Pigs
      were fed ad libitum before fasting. Heat production was measured using indirect
      calorimetry. Fasting heat production (FHP) was proportional to the body weight
      raised to the power 0.55, but with group-specific proportionality parameters
      (810, 1200, 1220 and 1120 kJ/kg BW0.55 per d for MC, LWC, LWM and PM
      respectively). Group effects could be removed by expressing FHP as a function of
      muscle, viscera and fat: FHP (kJ/d) = 457(muscle)0.81 + 1969(viscera)0.81 -
      644(fat)0.81. It is hypothesized that different breeds with equal muscle and
      visceral mass, can have different FHP. The negative coefficient for fat would
      then be the result of a low FHP rather than a cause of it. Because a large part
      of the variation in tissue composition between groups was due to MC group, a
      separate equation for the lean groups was established. For lean pigs, FHP could
      be expressed as a function of muscle and viscera alone: FHP (kJ/d) =
      508(muscle)0.66 + 2011(viscera)0.66. Both type of pig and BW affected the number
      of bouts of physical activities (i.e. standing or sitting) per day, the duration
      of activity and the total cost of activity. Energetic cost of activity was
      proportional to the muscle mass raised to the power 0.91 (FHPactivity (kJ/h
      activity) = 21.0(muscle)0.91). Physical activity represented less than 10% of the
      total heat production in fasting growing pigs housed alone in metabolic cages and
      kept in a quiet environment.

PMID- 9771339
TI  - The use of cumulative gas and volatile fatty acid production to predict in vitro
      fermentation kinetics of Italian ryegrass leaf cell walls and contents at various
      time intervals.
AB  - Differences between the fermentation characteristics of cell contents (CC) and
      protease-treated cell walls (CW) of young leaves of Italian ryegrass (Lolium
      multiflorum Lam.) cultivar Multimo (tetraploid), were studied in vitro. Gas and
      volatile fatty acid (VFA) production rates were measured at regular intervals, as
      was the degradability of organic matter (OM) of CW. The measured VFA were used to
      predict the gas production and fermentable OM using stoichiometric calculations.
      For CW the volume and kinetics of measured gas production were the same as those
      predicted from the VFA formed. In contrast, the measured gas production for CC
      was consistently less than predicted, indicating that the stoichiometric
      equations were not valid for rapidly fermenting substrates. For both CC and CW,
      the relative rate of acetic acid production levelled off more slowly than for
      other VFA, resulting in an increasing gas yield (in ml/g fermentable OM) after 12
      (CW)-24 (CC) h incubation. Consequently, the fermentation of OM was not linearly
      related to gas production kinetics. For CW, the kinetics of decline of degradable
      OM and fermentable OM were the same, after correction for a constant 'lost
      fraction' of degradable OM of 205 g/kg OM. This work indicates the value of
      detailed studies of fermentation processes to evaluate herbage quality. In
      particular, the role of CC and the difference between degradation and
      fermentation require further attention.

PMID- 9771340
TI  - Rat adipose tissue rapidly accumulates and slowly releases an orally-administered
      high vitamin D dose.
AB  - We investigated the effect of oral high-dose cholecalciferol on plasma and
      adipose tissue cholecalciferol and its subsequent release, and on plasma 25
      hydroxyvitamin D (25(OH)D). Female Wistar rats (n 126) received 37.5 micrograms
      cholecalciferol/d for 14 d and were subsequently studied for a further 88 d. Two
      subgroups of eighteen rats each were fasted for 3 d immediately after treatment
      (days 14-17) and at the end of the study (days 98-101). During treatment, plasma
      cholecalciferol increased rapidly to reach a steady-state. Plasma 25(OH)D and
      adipose tissue cholecalciferol increased linearly for 1-2 d after treatment.
      Serum Ca and inorganic phosphate also increased. Subsequently half-lives of
      plasma cholecalciferol and 25(OH)D, and perirenal and subcutaneous adipose tissue
      were: 1.4, 22.5, 97.5 and 80.9 d respectively. Fasting, as compared with ad
      libitum feeding, caused increased plasma free fatty acids, weight loss up to 14%
      and increased adipose tissue cholecalciferol (nmol/g wet weight). It did not
      affect plasma cholecalciferol immediately after cholecalciferol treatment, but
      raised plasma 25(OH)D. Fasting at the end of the study decreased plasma
      cholecalciferol and increased plasma 25(OH)D. We conclude that orally
      administered cholecalciferol rapidly accumulates in adipose tissue and that it is
      very slowly released while there is energy balance. Fasting causes preferential
      loss of triacylglycerols from adipose tissue, as opposed to cholecalciferol, but
      nevertheless augments plasma 25(OH)D. Adipose tissue may act as a 'buffer to
      functional vitamin D status' by preventing, to a certain extent, unregulated
      production of 25(OH)D from dietary vitamin D, and by slowly releasing vitamin D
      under fasting conditions.

PMID- 9771341
TI  - Comparison of oral and intraperitoneal iron supplementation in anaemic rats: a re
      evaluation of the mucosal block theory of iron absorption.
AB  - To evaluate the extent to which daily oral Fe supplements may block Fe absorption
      from a subsequent dose, we compared effects of oral and intraperitoneal (i.p.) Fe
      supplementation on Fe status in anaemic rats (haemoglobin (Hb) 90 g/l). A ligated
      duodenal loop technique was used to assess the effects of the Fe supplements
      administered either orally or i.p. at different frequencies on Fe absorption from
      a subsequent test dose. Anaemic Sprague-Dawley rats were assigned to seven groups
      of eight rats each and received either oral or i.p. Fe supplements for 3 d as
      follows: (1) 4 mg oral supplement daily (three doses in 3 d); (2) 4 mg oral
      supplement once (one dose on day 1, low-Fe dose on days 2 and 3); (3) 12 mg oral
      supplement once (one dose on day 1, low-Fe dose on days 2 and 3); (4) 3.2 mg i.p.
      supplement daily (three doses in 3 d); (5) 3.2 mg i.p. supplement once (one dose
      on day 1); (6) 9.6 mg i.p. supplement once (one dose on day 1); (7) low-Fe diet
      (control). The effectiveness of the supplements in treating Fe deficiency on each
      of the two test-factors, i.e. route of administration and frequency of dose, was
      assessed by determining Hb-Fe gain and liver-Fe stores after the 3 d test period.
      Oral supplementation was as effective as i.p. in improving the Fe status of the
      anaemic animals. However, a 15 min absorption of a radio-Fe test dose from a
      ligated loop in i.p.-supplemented groups was significantly higher (11.68 (SD
      1.70)%, 17.49 (SD 4.59)%, 16.71 (SD 3.39)%) than in orally supplemented groups
      (3.24 (SD 1.35)%, 2.45 (SD 1.05)%, 1.80 (SD 0.35)%) despite equal body Fe stores.
      No significant difference in intestinal Fe absorption efficiency was detected
      within the oral groups but those supplemented only once were more effective than
      or as effective as the group receiving daily supplements for 3 d in improving Fe
      status as indicated by Hb-regeneration efficiency. We conclude that there is a
      mucosal block with the administration of oral Fe supplements but the extent of
      this blocking effect during oral Fe supplementation is not as dramatic as
      currently thought in the context of the poor efficacy of daily Fe supplementation
      programmes.

PMID- 9771342
TI  - Importance of measuring CO2-production rate when using 13C-breath tests to
      measure fat digestion.
AB  - Stable isotope breath tests offer a safe, repeatable non-invasive method of
      measuring fat digestion. They involve the ingestion of a substrate labelled with
      13C followed by serial measurements of the 13C:12C ratio in expired CO2, from
      which the percentage of the 13C dose recovered (PDR) can be calculated. However
      PDR depends on the CO2-production rate. Our aim was to compare results obtained
      using directly measured CO2-production rates with those calculated from two
      predicted values. Twelve normal healthy children and twenty-four children with
      cystic fibrosis (CF) (without or with the normal dose of enzyme supplementation)
      were studied with 1,3-distearyl, 2[carboxyl-13C] octanoyl glycerol. The volume of
      CO2 produced (litres/min) was measured at rest for 30 min approximately 3 h after
      substrate ingestion, and the results were converted to mmol/min. For each subject
      the expected BMR was calculated from the equation of Schofield (1985), based on
      sex, age, weight and height, and from these values, CO2-production rate was
      derived. Surface area was calculated and an estimated value of 5 mmol/m2 per min
      (Shreeve et al. 1970) was used. Using these three CO2-production rates, three
      different PDR were calculated and compared. In healthy children there was a close
      concordance between measured and predicted CO2-production rates, but children
      with CF had a mean measured CO2-production rate 39% higher than normal children.
      This use of normal data for predicted CO2-production rates in children with CF
      underestimates cumulative PDR. If direct measurements of CO2-production rate are
      not available or impossible to perform the VCO2 obtained from the BMR calculated
      using the equations of Schofield (1985) or Shreeve et al. (1970) can be used in
      normal children. However, if accurate results for PDR are to be obtained, CO2
      production rates should be measured when performing breath tests in conditions
      where energy expenditure and/or CO2-production rate are not expected to be
      normal.

PMID- 9771343
TI  - Information technology in nutrition and dietetic education.

PMID- 9771345
TI  - Modified diagram of Friedman's symbolic representation of cleft lip and palate
      anomalies.
AB  - This paper describes the modification of the symbolic representation of Cleft Lip
      and Palate anomalies described by Friedman et al. These modifications were made
      in order to facilitate the computerisation of clinical records and database
      integration, and to improve the compliance and accuracy of cleft data collection.

PMID- 9771344
TI  - Prefabricated muscle flap including bone induced by recombinant human bone
      morphogenetic protein-2: an experimental study of ectopic osteoinduction in a rat
      latissimus dorsi muscle flap.
AB  - For skeletal reconstruction, a vascularised bone graft is both reliable and
      useful, but some sacrifice usually occurs at the skeletal donor site. In the
      search for our alternative, we investigated ectopic osteoinduction by bone
      morphogenetic protein in a rat muscle flap, to prefabricate a muscle flap that
      included bone. Right latissimus dorsi muscle flaps were prepared in 16 rats.
      Recombinant human bone morphogenetic protein-2 (rhBMP-2; 2, 10 and 50 micrograms)
      mixed with atelopeptide type I collagen (3 mg) as the carrier was wrapped with
      the tip of the latissimus dorsi muscle flap. Three weeks later, ectopic
      osteoinduction in the latissimus dorsi muscle flap was investigated
      radiologically, histologically and biochemically. A radiological oval shadow was
      observed in each animal in each rhBMP-2-implanted group. The volume of the oval
      shadow area in the muscle flap was dependent upon the dosage of rhBMP-2. It
      indicated that on ectopic osteoinduction by rhBMP-2 in the muscle flap, induced
      trabeculae were circularly constructed at the margins of the lump. The radio
      opacity of the oval shadows was almost equal in all rhBMP-2-implanted groups, and
      the shadow areas depended on the dosage of rhBMP-2. The biochemical indices of
      osteogenesis, ALP activity and Ca content in the lump were dependent upon the
      dosage of rhBMP-2. This study showed that ectopic osteoinduction occurred in the
      rat latissimus dorsi muscle flap and depended upon the dose of rhBMP-2. Wrapping
      rhBMP-2 mixed with atelopeptide type I collagen with the tip of a latissimus
      dorsi muscle flap could create a prefabricated muscle flap that included bone.

PMID- 9771346
TI  - Clinical evaluation of C7 spinal nerve transection: 21 patients with at least 2
      years' follow-up.
AB  - We have performed C7 spinal nerve transfer to treat root injury of the brachial
      plexus since 1989. Out of a total of 43 patients, 21 have been followed up for at
      least 2 years. Evaluation of the effect of C7 transection included clinical
      examination, intraoperative C7 stimulation, LIDO Workset machine and
      electrophysiological studies to test C7 innervated muscles, and histochemical
      analysis of the anterior and posterior division of the upper trunk using
      acetylcholinesterase stain. Nearly half of the study group (48%) reported no
      significant sensory changes and most patients (81%) did not notice any weakness
      of the limb following C7 transection. Some patients did experience sensory and
      motor abnormalities which were most frequent during the first postoperative
      month, improved during the 2nd month and in most cases resolved in the 3rd
      postoperative month. The only longer persistent abnormality was the triceps
      reflex, which becomes weak or absent. We also found that intraoperative C7
      stimulation was a useful predictor of possible post-transection morbidity.
      Subclinical deficits, detected by the LIDO workset machine and by electro
      physiological studies, were quite common. Histochemical analysis revealed that
      the posterior division of C7 had more motor fibres than the anterior division.

PMID- 9771347
TI  - Long-term studies of cold-stored rabbit femoral artery and vein autografts.
AB  - In previous studies we have shown that 80-100% of rabbit femoral vascular
      autografts cold-stored at 4 degrees C for 3 weeks remain patent 3 weeks after
      reinsertion in the femoral artery. The present study reports the effect on graft
      patency of increasing either the period of cold storage prior to reinsertion or
      the duration of reperfusion to 6 months. Rabbit femoral blood vessels were cold
      stored (CS) at 4 degrees C for varying periods. CS autografts were reinserted
      into the contralateral leg for 3 weeks or 6 months. Graft patency was determined
      and grafts examined by histological, immunohistochemical and electron
      microscopical techniques. Six months after reinsertion patency of 4-week CS
      arterial and 1-week CS venous grafts was 40% and 27% respectively, very much
      lower than the 80-100% seen after 3 weeks reperfusion. Arterial grafts CS for 6
      months had a patency rate of 70% after 3 weeks reperfusion but 0% after 6 months.
      Morphological examination suggests that the delayed failure of cold-stored
      vascular grafts is caused by thrombus superimposed on intimal hyperplasia within
      the graft. CONCLUSIONS: Cold-stored vascular grafts are useful prostheses when
      only 3-4 weeks graft patency is required. They are not suitable for use when long
      term graft patency is needed.

PMID- 9771348
TI  - An electrophysiological and morphological comparison of the microwave muscle
      graft and the freeze-thawed muscle graft.
AB  - The purpose of this study was to assess the feasibility of using a microwave oven
      to produce denatured muscle grafts for the repair of 1 cm deficits in the rabbit
      peroneal nerve. Recovery of function was assessed after 6 months by
      electrophysiological and histological examination of the peroneal nerve and
      target muscles. The results were compared to normal rabbits and to a group whose
      nerves were repaired with freeze-thawed muscle grafts (FTMG). The results of this
      study showed that heating muscle in a microwave oven does produce a graft which
      may be used as an alternative to the FTMG. However, the technical difficulties in
      preparing a microwave muscle graft make the use of this technique in the clinical
      setting unlikely.

PMID- 9771349
TI  - Closure of the skin defect overlying infected non-union by skin traction.
AB  - Skin traction based on an Ilizarov frame has been used to achieve skin closure in
      five cases of infected non-union of the tibia including one case of infected knee
      arthrodesis. Five patients presented with infected non-union of the tibia (all
      Staph. aureus, two of them MRSA) with overlying sinuses discharging pus at an
      average 16 months from injury (range 3-36 months). The infections were treated by
      excision of the sinus and infected skin, excision of the infected non-union,
      stabilisation of bone with an Ilizarov circular frame and either acute shortening
      with compression followed by distraction (3 patients), or bone transport (2
      patients). After excision of the sinus, the skin defect was gradually closed
      using a skin traction device placed on an Ilizarov circular frame. The size of
      the wounds ranged from 5 x 14 cm to 3 x 5 cm and skin traction was completed at 4
      weeks (range 2-8 weeks). When the wound edges were approximated, the wires were
      left in place until healthy granulation tissue built up to seal the remaining gap
      (sutures were used in two patients). At follow-up assessment at 18 months (range
      7-24 months), all non-union were solidly united with no signs of infection of
      either the bone or underlying skin. The quality of skin at the stretching site
      was found to be of normal sensation, colour, mobility but thinner than normal.
      The quality of the skin at the docking site (left to granulate) was found to be
      adherent to the underlying bone, red or pink in colour, hypersensitive in 2
      patients and numb in 3 patients.

PMID- 9771350
TI  - Breast implants: a survey of cosmetic clinics.
AB  - The quality of information available to prospective cosmetic breast implant
      recipients in the private sector was assessed. Sixteen women telephoned 14
      clinics requesting written information about breast implants and their safety.
      The information received varied enormously in quality. Of the purely cosmetic
      clinics offering information, it was generally of better quality and more
      consistent than private hospitals where accredited plastic surgeons operate. In
      the current climate of consumer choice and negative attention given to silicone
      breast implants by the media, more comprehensive information should be readily
      available to guide potential patients.

PMID- 9771351
TI  - Functional reconstruction of forehead with microneurovascular transfer of
      attenuated and broadened gracilis muscle.
AB  - Reconstruction of the frontalis muscle is difficult because it is very thin and
      broad. A technique is described to reconstruct the frontalis muscle with
      microneurovascular transfer of the gracilis muscle broadened and thinned. This
      technique is applicable to cases with a large, full-thickness skin defect of the
      forehead after tumour excision or trauma.

PMID- 9771352
TI  - Ceruminous gland neoplasia.
AB  - Ceruminous glands are modified sweat glands, confined to the skin lining of the
      cartilaginous part of the external auditory meatus. Tumours arising from these
      glands are extremely rare. Confusion exists regarding the nomenclature
      'ceruminoma' and controversies prevail on the standard way of management.
      Treatment often involves a multidisciplinary approach, requiring reconstruction
      after extensive surgical resection. A case report of adenoid cystic carcinoma of
      ceruminous glands is presented along with discussion of the various pathological
      types and a review of management.

PMID- 9771353
TI  - Congenital ectopic nail with bone deformity.
AB  - This report describes two cases of congenital ectopic nail with bone deformity.
      Histologically, the squamous epithelium of the nail matrix lacked a definite
      granular layer. Resected nail tissue was connected with the periosteum of the tip
      of the ungual phalanx, which suggested that the contact of the ectopic nail
      matrix with the periosteum could impede intramembranous ossification and deform
      the bone shape.

PMID- 9771354
TI  - Training of overseas doctors in plastic surgery.

PMID- 9771355
TI  - Suppurative tenosynovitis revisited.

PMID- 9771356
TI  - The further uses of the surgical glove.

PMID- 9771357
TI  - History of the West of Scotland Plastic Surgery Unit: 1940-1986.

PMID- 9771358
TI  - Maxillary distraction osteogenesis in Pfeiffer's syndrome: urgent ocular
      protection by gradual midfacial skeletal advancement.
AB  - Distraction osteogenesis is increasingly recognised as a potentially useful
      technique to achieve the co-ordinated augmentation of craniofacial skeletal and
      soft tissue. A case is presented where bilateral maxillary distraction was
      successfully used to advance the midface in the treatment of recurrent ocular
      dislocation, in a 10-month-old boy with Pfeiffer's syndrome.

PMID- 9771359
TI  - Combined anterior thigh flaps and vascularised fibular graft for reconstruction
      of massive composite oromandibular defects.
AB  - Six massive, composite oromandibular defects were reconstructed using combined
      anterior (anterolateral and anteromedial) thigh flaps and vascularised fibular
      graft in bridge or chimeric fashion. Except for minor dehiscence in one case and
      infection in another, all flaps survived without complication. Anterior thigh
      flaps provide large-calibre, long vascular pedicles while derivative branches
      from the lateral circumflex femoral system facilitate simultaneous
      transplantation of multiple components. Because the pedicle of the vascularised
      fibular graft is of insufficient length, the lateral circumflex femoral vessels
      provide a remote vascular source as a flow-through vascular conduit. A combined
      flap using the lateral circumflex femoral system is considered to be most
      suitable for reconstruction of through-and-through defects of the head and neck.
      The authors describe the advantages of this method and the detailed anatomy of
      the cutaneous perforators of the anterior thigh flaps.

PMID- 9771360
TI  - Secondary lengthening of the reconstructed mandible using a gradual distraction
      technique--two case reports.
AB  - We have performed mandibular lengthening to restore oral function in 2 cases
      after tumour resection. Both cases had already undergone a vascularised fibular
      graft for mandibular reconstruction and had severe contracture and absence of an
      alveolar ridge for dentures. Gradual distraction was applied after corticotomy of
      the fibular bone at 0.9 mm per day. After completion of bone lengthening of 20-30
      mm, both patients underwent a split thickness skin graft to obtain a good
      alveolar ridge for dentures and implants. Osteointegrated implants have since
      been applied in one of these cases, and the other patient has been able to eat a
      normal diet using dentures. Gradual distraction is applicable for vascularised
      bone grafts and useful for restoration of the alveolar ridge to accommodate
      dentures in cases with severe contracture of the oral space after tumour
      ablation.

PMID- 9771361
TI  - Surgical correction of the cauliflower ear.
AB  - The cauliflower ear presents a challenge to the surgeon. Patients complain of
      discomfort and appearance. Three patients were treated surgically via a posterior
      approach to remove the hardened segment and re-sculpture a leaf of cartilage left
      in place. An acceptable cosmetic result was achieved and all patients are
      currently pain free.

PMID- 9771362
TI  - Versatility of modified planimetric Z-plasties in the treatment of scar with
      contracture.
AB  - The planimetric Z-plasty proposed by Roggendorf provides elongation by excision
      of a pair of triangular pieces of tissue. The application of planimetric Z
      plasties has been modified by making the vertical angle flexible, and making them
      continuous in the same or in opposite directions. Continuous planimetric Z
      plasties in the same direction elongate an oblique contracture in the
      longitudinal direction. Continuous planimetric Z-plasties in an alternative
      direction elongate a disproportioned scar contracture in the longitudinal
      direction. Both techniques partially reduce unsightly scarring. Furthermore, they
      can be used in combination with V-Y-plasties. These modifications permit rational
      planing of the treatment of complicated scars with contracture.

PMID- 9771363
TI  - A 5-year audit of trainees experience and outcomes with two-stage hypospadias
      surgery.
AB  - The results of a 5-year audit of trainee plastic surgeons' experience and
      outcomes with two-stage hypospadias surgery are presented. Between June 1991 and
      October 1996, 87 patients had at least one of their operations performed by
      trainees; 79 patients had completed their surgery and were available for study.
      All patients underwent two-stage hypospadias correction; median duration of
      follow-up was 707 days. 69.5% of patients required correction of glans tilt
      and/or chordee correction; a small meatus was present in 62%. Trainees performed
      73.2% of the first stage surgery (23.2% supervised by the consultant and 50% as
      most senior surgeon). The total complication rate for the first stage was 6.1%;
      the complications were: residual chordee and/or insufficient skin graft take (4
      cases) and haematoma (1 case). Trainees performed 58.2% of the second stage
      surgery (24.1% supervised by the consultant and 34.2% as most senior surgeon).
      The fistula rate for the trainee stage 2 cases was 15.2% and the stricture rate
      4.3%. All fistulae and strictures were successfully treated by one additional
      procedure. Complications rates for the first stage were similar between grades;
      consultant 4.5%; supervised trainee 5.3% and unsupervised trainee 7.3%. However,
      unsupervised trainees had a much higher complication rate for the second stage:
      29.6%, versus consultant 3.0% and supervised trainee 5.3%. These complication
      rates represent the cumulative learning curve of 17 trainee surgeons. Outcomes
      for two individual trainees after the same number of cases (47) were studied
      further. These trainees had the highest and lowest complication rates for the
      procedure; 24% versus 9%. These figures might better reflect the range of the
      learning curve of this procedure. A major difference between these two trainees
      was the time taken to accrue 47 cases; 15 months versus 25. In the former case
      this concentration of training was felt to be beneficial. Further analysis of one
      trainee's results suggested that complications occur early in the learning curve
      and with appropriate supervision acceptable complication rates can be achieved.

PMID- 9771364
TI  - Glans sculpting in phalloplasty--experiences in female-to-male transsexuals.
AB  - An aesthetically appealing neophallus with an urethral meatus at its tip is one
      of the goals of phalloplasty in female-to-male transsexuals. From July 1993 to
      December 1996, 20 cases of female-to-male transsexuals who had received sculpting
      of glans in four different ways were enrolled. Their photographs were collected
      and were scored by independent surgical and non-surgical assessors. The Norfolk
      procedure creates a more normal neoglans assessed by patients themselves and by
      the assessors. Split-thickness skin graft (SSG) produces a more normal-looking
      coronal sulcus than full-thickness skin graft (FTSG) in the Norfolk procedure.

PMID- 9771365
TI  - Measuring quality of life in cosmetic surgery patients with a condition-specific
      instrument: the Derriford Scale.
AB  - OBJECTIVE: To assess the reliability, validity and sensitivity to change of the
      Derriford Scale, a quality of life instrument designed to assess the distress and
      dysfunction experienced by people who are self-conscious about their physical
      appearance. SUBJECTS AND DESIGN: Postal questionnaire survey of 656 cosmetic
      surgery patients recruited from new referral letters and plastic surgery waiting
      list reports. A total of 443 subjects completed and returned the questionnaire.
      Of these respondents, 203 were sent a second questionnaire to assess
      reproducibility, of whom 155 subjects responded. MAIN OUTCOME MEASURES:
      Reliability was assessed in terms of internal consistency and reproducibility.
      Face, content and construct validity were also investigated. RESULTS: The
      analyses led to mixed results. There was some evidence of internal consistency,
      but a number of items had low endorsement levels and there may be scope for
      reducing the overall size of the instrument. When assessed for reproducibility,
      the level of agreement between scores of individuals completing the questionnaire
      on two occasions was high, but an important systematic shift in responses was
      also detected. Correlations between the other health status measures and the
      Derriford Scale provided some evidence of construct validity. CONCLUSION: In its
      present form the Derriford Scale has good descriptive value, but there are some
      measurement problems identified in this report that need to be addressed before
      the scale is taken up into general use.

PMID- 9771366
TI  - Randomised control trial of pH buffered lignocaine with adrenaline in outpatient
      operations.
AB  - Bicarbonate buffering of local anaesthetics is known to significantly decrease
      the pain of their administration and yet few practising surgeons do so. A double
      blind randomised cross-over clinical trial was conducted to confirm the
      practicality and efficacy of bicarbonate buffering of lignocaine with adrenaline
      in the setting of a busy local anaesthetic operating theatre. 40 patients
      received either buffered or control local anaesthetic solutions in equivalent
      sites on opposite sides of the body. The pain of each injection was rated from 0
      (no pain) to 10 (extreme pain). The mean pain score for the buffered solution was
      significantly lower than the control solution (3.06 vs 4.34, P = 0.002).
      Bicarbonate buffering of lignocaine with adrenaline is effective, inexpensive and
      simple; its widespread use should be encouraged.

PMID- 9771367
TI  - Hormone responses to stress in patients with major burns.
AB  - The responses of the plasma stress hormones corticotrophin (ACTH), vasopressin
      (AVP), cortisol and corticotrophin releasing hormone (CRH) have been studied in
      seven consecutive patients aged between 15 and 65 years who suffered from burns
      of 15-95% total body surface area. There was a distinct peak in AVP (up to 100
      pmol/l) and ACTH levels well above the upper limit of normal in all except one
      patient within 24 h of burn injury. Following the initial rise, AVP and ACTH
      tended to fall. Plasma CRH with one exception remained within the normal range.
      Concurrent measurement of plasma renin activity (PRA), haemoglobin (Hb),
      haematocrit (Hct) and plasma sodium (Na), to assess hydration, showed that PRA
      was increased in all except one patient during the first 4 days of hospital
      admission. The correlation between ACTH and cortisol was highly significant (P <
      0.001), as was the correlation between ACTH and AVP, AVP and Na, PRA and Hb, and
      Hct and Na. Other significant correlations were ACTH and Hct (P = 0.023), ACTH
      and Na (P = 0.017), AVP and Hct (P = 0.029), CRH (P = 0.018), CRH and Hb (P =
      0.001). No significant correlation could be demonstrated between CRH and ACTH or
      AVP. Our findings suggest that AVP plays a role in the hypercortisolaemia which
      accompanies major burns. The possible detrimental effect of very high levels of
      AVP leading to progression of burn depth and reduction of skin graft take by its
      potent vasoconstrictive action and water retention effect (resulting in oedema)
      deserves further study. As AVP has the potential to reduce tissue perfusion, the
      possible use of antagonists in major burns merits further consideration.
      Persistently raised PRA levels, despite normal biochemical and haematological
      parameters, may indicate that volume expansion therapy may not be adequate, and
      that both hypovolaemia and stress may contribute to the AVP response. Stress
      hormone monitoring may lead to better treatment and a reduction in burn stress.

PMID- 9771368
TI  - Expansion of venous flaps: an experimental study in rats.
AB  - In this study, the effects of controlled tissue expansion on the survival of
      unipedicled venous flaps were investigated in rats. In three groups of Lewis
      rats, a 3 x 6 cm unipedicled Lateral thoracic venous flap was studied with group
      1 as control group (n = 30) without any manipulation, group 2 (n = 30) where an
      expander was introduced under the flap area but was not expanded and group 3 (n =
      30) in which a 40 ml expander was introduced under the flap area and was expanded
      over a period of 10 days. Observations included gross and histological
      examination, reverse microangiography, reverse flow resistance and percentage of
      survival of flaps. Group 3 (expanded) showed more angiogenesis, a better
      delineation on microangiography, lower reverse flow resistance and higher
      survival rates as compared to group 2 (non-expanded). In the control group the
      survival rate of flaps was the poorest and the flaps showed higher rates of
      reverse flow resistance. Microangiography was not successful in the control
      group. In a pilot project prior to this experiment microscopic examination of the
      Lateral thoracic vein in 10 Lewis rats had confirmed the presence of two or three
      valves in this vein.

PMID- 9771369
TI  - Cutaneous meningioma of the scalp: a case report and review of literature.
AB  - Ectopic meningioma outside the skull and spinal column is uncommon. We report a
      cutaneous meningioma of the scalp in a 77-year-old man. A review of types and
      their management options are discussed. We also highlight that in certain
      carefully selected cases, these lesions can be treated conservatively.

PMID- 9771370
TI  - Compartment syndrome in a free fibula osteocutaneous flap donor site.
AB  - Donor site morbidity for free fibula microvascular flaps is generally reported to
      be low and considered to be minor. We describe a case where the major
      complication of compartment syndrome occurred in a 15-year-old boy when the donor
      site defect was closed primarily after taking a skin paddle with a width of 4 cm.
      We recommend that when harvesting free fibula flaps in children, skin grafting of
      donor site should be considered irrespective of the width of the flap, if there
      is any doubt about the tightness of the closure.

PMID- 9771371
TI  - Saphenous nerve neuralgia after gracilis muscle flap harvest.

PMID- 9771372
TI  - Giant congenital cellular blue naevus of the scalp and cranium.

PMID- 9771373
TI  - Immunosuppression following thermal injury.

PMID- 9771374
TI  - Closed method of dilute adrenaline infiltration in reduction mammoplasty.

PMID- 9771376
TI  - The impact of outpatient department wall charts on physician compliance with skin
      cancer follow-up protocols.

PMID- 9771375
TI  - Silicone breast implants: complications.

PMID- 9771377
TI  - Pubis osteomyelitis treated with a turn-over rectus abdominis flap.

PMID- 9771378
TI  - Helium-3 imaging of pulmonary ventilation.

PMID- 9771379
TI  - Signal-to-noise ratio in MRI.

PMID- 9771380
TI  - Image processing and spiral CT of the thorax.
AB  - The data set of the thorax acquired by spiral CT is volumetric. Such data can be
      processed so that conventional axial sections are supplemented by reconstructed
      images, in an attempt to answer specific clinical questions. This review
      considers three reconstruction techniques: multiplanar reformation, three
      dimensional rendering and sliding-thin slab reconstruction. Their relative
      benefits and limitations are considered, as are the implications of image
      processing in general.

PMID- 9771381
TI  - Radiology of adjustable silicone gastric banding for morbid obesity.
AB  - We reviewed the radiological findings in 45 morbidly obese patients (weight range
      80-129 kg; mean 95.7 kg) after gastric restriction surgery with adjustable
      silicone gastric banding (ASBG) according to the Kuzmak technique. Radiographic
      studies of the stomach were performed before, and at 4 and 12 months after
      surgery; symptomatic patients underwent additional studies when needed. Patients
      were evaluated using both liquid barium and a solid opaque meal to assess post
      operative gastric morphology as well as emptying time of the proximal gastric
      pouch. 27 patients had a normal clinical course. Variation of the calibre of the
      silicone band under radiographic guidance was required in 12 of these patients,
      based on dilatation of the proximal pouch, variation of the stomal calibre from
      operative values, or an emptying time longer than 30 min. All these problems
      disappeared after the adjustment manoeuvres. 18 patients had complications, of
      which five had stomal stenosis which could not be managed through simple
      deflation of the band; two had posterior bending and dilatation of the proximal
      pouch; four had gastritis and oesophagitis; six had infection of the inflatable
      reservoir; one had cranial displacement of the band, and two had migration of the
      band into the stomach. Removal of the gastric band was necessary in 11 cases, and
      removal of the reservoir alone had to be performed in three additional patients.
      Radiology plays an important role in evaluating complications after gastric
      restriction surgery. Knowing the variety of findings enables accurate treatment
      planning and follow-up of these patients.

PMID- 9771382
TI  - Ultrasound guided fine needle aspiration cytology in abdominal tuberculosis.
AB  - Although barium studies and CT are useful in assessing abdominal pathology in
      tuberculosis, imaging findings are not always specific and a histopathological or
      bacteriological confirmation is often required. The aim of the present study was
      to evaluate the role of ultrasound (US) guided fine needle aspiration cytology
      (FNAC) in the diagnosis of abdominal tuberculosis in patients with non-palpable
      lesions detected on US/CT. FNAC was performed on 31 sites in 30 patients. The
      sites included enlarged lymph nodes (n = 14), focal lesions in liver (n = 2) and
      spleen (n = 8), and thickened bowel in the ileocaecal region (n = 7). The results
      were classified cytomorphologically into four groups: (1) definite evidence of
      tuberculosis; (2) presumptive evidence of tuberculosis; (3) suggestive of
      tuberculosis; and (4) negative for tuberculosis. 18 of the 31 FNACs (58%)
      revealed a positive diagnosis of tuberculosis (definite evidence in nine patients
      and presumptive evidence in nine patients). 13 of the 31 FNACs (42%) showed
      either necrosis alone (n = 4) or negative results (n = 9). Zeihl-Neelson staining
      for acid-fast bacilli on direct smear was positive in only nine patients (29%).
      Splenic and lymph nodal FNAC had a high sensitivity (87.5% and 78.6%,
      respectively) in the diagnosis of tuberculosis. None of the bowel and liver FNACs
      was diagnostic. No complications were encountered. US guided FNAC offers a safe
      and accurate method of achieving a diagnosis in patients with suspected abdominal
      tuberculosis who present with radiologically demonstrable but non-palpable
      lesions, especially those involving lymph nodes and spleen.

PMID- 9771383
TI  - Lens injuries induced by occupational exposure in non-optimized interventional
      radiology laboratories.
AB  - Several cases of ophthalmologically confirmed lens injuries, caused by
      occupational radiation exposure, have occurred in two X-ray rooms devoted to
      vascular and visceral interventional radiology procedures. Both laboratories were
      equipped with overcouch X-ray systems not designed for interventional radiology
      and without specific tools for radiation protection of the eyes. Typical
      workloads ranged from between two and five procedures per day. For the two
      radiologists affected, estimates for the dose to eye lens ranged from 450 to 900
      mSv per year, over several years. Once the incidents had been detected, the X-ray
      systems in both rooms were removed and new equipment specifically designed for
      interventional radiology was installed, including suspended shielding screens.
      Since these lens injuries were only detected accidentally, measures to avoid
      similar occurrences in the future are discussed.

PMID- 9771384
TI  - Radiation dose and image quality in spiral computed tomography: multicentre
      evaluation at six institutions.
AB  - The purpose of this study was to evaluate the correlation of radiation dose with
      image quality in spiral CT. Seven clinical protocols were measured in six
      different radiological departments provided with four different types of high
      specification spiral CT scanners. Central and surface absorbed doses were
      measured in acrylic. The practical CT dose index (PCTDI) was calculated for seven
      clinical examination protocols and one standardized protocol using identical
      parameters on four different spiral CT scanners with a dedicated ionization
      chamber inserted into PMMA phantoms. For low contrast measurements, a cylindrical
      three-dimensional (3D) phantom (different sized spheres of defined contrast) was
      used. Image noise was measured with a cylindrical water phantom and high contrast
      resolution with a Perspex hole phantom. Image quality phantoms were scanned using
      the parameters of the clinical protocols. Images were randomized, blinded and
      read by six radiologists (one from each institution). PCTDI values for four
      different scanners varied up to a factor between 1.5 (centre) and 2.2 (surface)
      for the standardized protocol. A greater degree of variation was observed for
      seven clinical examination protocols of the six radiological departments. For
      example, PCTDI varied up to a factor between 1.7 (cerebrum protocol) and 8.3
      (abdomen paediatric protocol). Low contrast resolution correlates closely with
      dose. An improvement in detection from 8 mm to 4 mm sized spheres needs
      approximately a ten-fold increase in dose. Noise shows a moderate correlation
      with PCTDI. High contrast resolution of clinical protocols is independent of
      PCTDI within a certain range. Differences in modern CT scanner technology seem to
      be of less importance for radiation exposure than selection of protocol
      parameters in different radiological institutes. Future discussion on guidelines
      regarding optimal (patient adapted) tube current for clinical protocols is
      desirable.

PMID- 9771385
TI  - A comparison of patient dose for examinations of the upper gastrointestinal tract
      at 11 conventional and digital X-ray units in The Netherlands.
AB  - The objective of this study was to derive the effective dose to patients from
      examinations of the upper gastrointestinal (GI) tract at 11 X-ray units in 10
      Dutch hospitals. Entrance dose and entrance dose rate were measured at the
      surface of a homogeneous PMMA phantom and at the entrance surface of the image
      intensifier. Dose-area products (DAPs) were assessed during examinations of
      patients. The patients (334 females and 256 males) ages were 18-95 years (average
      52 years). Effective dose was assessed from DAP using Monte Carlo computer
      calculations for male and female mathematical anthropomorphic phantoms. The DAPs
      measured during the survey showed substantial variations, i.e. an overall average
      value of 21 Gy cm2 and a range of average DAP per X-ray unit varying from 7 to 56
      Gy cm2. Variations in the number of images (8-28) and the fluoroscopy time (1.7
      min-7.0 min) were also large. A DAP to effective dose conversion factor of 0.32
      mSv Gy cm-2 was derived for upper GI studies. The dose survey yielded an overall
      average effective dose of 6.7 mSv. At one location an examination involving as
      many as 28 projections was performed, whilst maintaining a DAP well below 15 Gy
      cm2 and an effective dose below 6 mSv. This was achieved using modern equipment
      (i.e. high frequency generator, digital spot films) with 0.2 mm additional copper
      filtration and a relatively high tube voltage. For examinations of the upper GI
      tract, the application of a reference value of 30 Gy cm2 for the DAP will ensure
      that, in general, the effective dose to individual patients will not exceed 15
      mSv.

PMID- 9771387
TI  - Contribution of the cortical shell of vertebrae to mechanical behaviour of the
      lumbar vertebrae with implications for predicting fracture risk.
AB  - In the diagnosis of osteoporosis using single energy quantitative CT (SE-QCT) on
      the axial skeleton, only spongy bone mineral density (BMD) is used at present.
      Although the density of cortical bone is also determined by most QCT methods, it
      is not used for evaluation. The objective of this study was to determine the
      extent to which the cortical bone of the lumbar vertebral bodies accounts for
      their load-bearing capacity and failure behaviour, and to use this information to
      suggest improvements in the differential diagnosis of osteoporosis.
      Investigations were conducted in a clinical, theoretical-numerical and
      biomechanical-experimental context. Cortical (BMDC) and spongy (BMDS) bone
      mineral density was measured by SE-QCT/85 kV on 179 patients (68 males, 111
      females). These bone densities were matched with the vertebral body fractures
      previously determined from conventional X-rays. A finite element model was used
      to study the variation in structural and material parameters of the vertebral
      body. 19 vertebral bodies that had been removed post-mortem were available for
      the biomechanical-experimental investigations. Spongy and cortical bone densities
      were also determined by SE-QCT on these vertebral bodies. Their failure load was
      then measured in the axial compression test. These investigations show that, in
      addition to the spongiosa, the cortical shell plays an important role in the load
      bearing capacity of the vertebral body. If the spongiosa is weakened due to a
      loss of BMD, the residual load-bearing capacity of the vertebral bodies is
      increasingly shouldered by the cortical bone. The lower susceptibility to
      fracture in men compared with women when spongy bone mineral density is reduced
      can thus be attributed to the lack of a reduction in cortical bone mineral
      density. It is recommended that the BMDC also be evaluated in future, especially
      in the diagnosis of bone mass losses in women, to improve the estimation of the
      individual fracture risk.

PMID- 9771386
TI  - Bone mass assessment in rats by dual energy X-ray absorptiometry.
AB  - At present there are many techniques available for determining bone mass,
      measurement of which is essential for monitoring osteopenia. Rats are preferred
      to other laboratory species when designing animal studies on osteoporosis. The
      precision and accuracy of dual energy X-ray absorptiometry (DXA) for the
      assessment of bone mineral density (BMD) and bone mineral content (BMC) in
      laboratory animals were assessed. Precision, expressed as a coefficient of
      variation (CV), was measured, making five determinations (Hologic QDR-1000) on
      lumbar spine (in vivo) and femur (in vitro), both with and without repositioning.
      The correlation (r) between densitometric parameters and mineral content of bone
      ashes was calculated both in lumbar spine (in vivo) and in femur (in vitro). In
      our study, DXA had good precision, better in femur (CV 0.53%) than in lumbar
      spine (L2-L4) (CV 1.0%). Repositioning did not increase significantly the
      coefficients of variation (CV 0.61% and 1.2%, respectively). The linear
      regression between BMD and ash weight, calcium and phosphorous content showed
      high correlation coefficients (r = 0.64-0.85, p < 0.05). Although we found an
      overestimate of values of BMC with respect to ash weight (21% in lumbar spine and
      31% in femur), the correlation between BMC and mineral content was high (r = 0.96
      0.99, p < 0.05). The results suggest that the DXA technique has the precision
      necessary when used to assess BMD and BMC in small laboratory animals.

PMID- 9771388
TI  - An experimental method to determine the effective luminescence efficiency of
      scintillator-photodetector combinations used in X-ray medical imaging systems.
AB  - The scintillator effective luminescence efficiency, which may be defined in terms
      of the scintillator's X-ray luminescence efficiency and the scintillator
      photodetector spectral matching and geometrical configuration, was studied for
      various X-ray imaging applications. Four scintillator materials Gd2O2S:Tb,
      Y2O2S:Tb, ZnSCdS:Ag and CsI:Na were used to prepare test screens. They were
      evaluated in relation to various photodetectors used in X-ray imaging, such as
      radiographic films, photocathodes, and photodiodes. Effective luminescence
      efficiency was determined for a range of X-ray tube voltages (50-140 kVp) by
      measuring the light flux emitted per unit of incident exposure rate and the
      spectra of the light emitted by the four scintillators. Scintillator
      photodetector combinations resulting in higher image brightness level were
      determined for different X-ray imaging systems. Findings indicate that CsI:Na is
      very efficient with orthochromatic radiographic films, Gd2O2S:Tb could be useful
      in conventional or digital fluoroscopy and in CT and ZnSCdS:Ag could be employed
      in some medium to low voltage digital radiography applications.

PMID- 9771389
TI  - Evaluation of carborane-containing porphyrins as tumour targeting agents for
      boron neutron capture therapy.
AB  - A number of carborane-containing porphyrins were administered to mice bearing
      subcutaneously transplanted mammary carcinomas. Administration was via serial
      intraperitoneal (i.p.) injections to assess their relative toxicities and tumour
      affinities. Three analogues of the natural porphyrin heme and four
      tetraphenylporphyrins (TPPs) were given at total doses of 78-245 micrograms g-1
      body weight. The water-insoluble TPPs were less toxic to mice, and delivered
      greater amounts of boron to tumour than did the water-soluble TPPS and the heme
      analogues. One such compound, NiTCP-H, delivered more than 100 micrograms B g-1
      to tumour tissue with a tumour:blood boron concentration ratio greater than 500:1
      and a tumour: brain boron concentration ratio greater than 50:1, 4 days after the
      last of six i.p. injections given over 2 days. Another TPP analogue, NiTCP,
      delivered approximately 50 micrograms B g-1 to tumour with similar boron
      concentrations in normal tissues. Neither compound was toxic to mice at total
      doses of approximately 200 micrograms g-1 body weight. In contrast, the heme
      analogues were toxic and, with the exception of VCDP, delivered less boron to
      tumour than NiTCP and NiTCP-H. The two porphyrins with the greatest potential for
      application to boron neutron capture therapy (BNCT), NiTCP and NiTCP-H, yielded
      higher tumour:blood and tumour:brain boron concentration ratios in mice than
      could be achieved with p-boronophenylalanine (BPA) and sodium
      mercaptoundecahydrododecaborate (BSH), the compounds which are currently being
      used in clinical trials of BNCT in the treatment of glioblastoma. The boron
      delivered by each of the porphyrins tested remained in tumour tissue longer than
      did boron delivered by either BPA or BSH. The copper and nickel chelates of these
      porphyrins behave identically in vivo. The former offer the potential for imaging
      by 67Cu-mediated single photon emission computed tomography (SPECT) to aid BNCT
      treatment planning.

PMID- 9771390
TI  - A comparative study of radioprotection by Ocimum flavonoids and synthetic
      aminothiol protectors in the mouse.
AB  - The radioprotective effects of two flavonoids, orientin (Ot) and vicenin (Vc),
      obtained from the leaves of Ocimum sanctum, and the synthetic compounds WR-2721
      and MPG (2-mercaptopropionyl glycine) have been compared by examining chromosome
      aberration in cells of bone marrow in irradiated mice. Healthy adult Swiss mice
      were injected intraperitoneally (i.p.) with 50 micrograms kg-1 body weight of Ot
      or Vc; 20 mg kg-1 of MPG; 150 mg kg-1 of WR-2721 or double distilled water (DDW).
      They were exposed to whole body irradiation of 2.0 Gy gamma radiation 30 min
      later. After 24 h, chromosomal aberrations were studied in the bone marrow of the
      femur by routine metaphase preparation after colchicine treatment. Radiation (2
      Gy) increased the number of aberrant cells from less than 1% in controls to
      almost 20%. Pre-treatment with all the protective compounds resulted in a
      significant reduction in the percentage of aberrant metaphases as well as in the
      different types of aberration scored. Vc produced the maximum reduction in
      percent aberrant cells while MPG was the least effective; Ot and WR-2721 showed
      an almost similar effect. However, WR-2721 was the most effective against
      reduction of complex an almost similar effect. However, WR-2721 was the most
      effective against reduction of complex aberrations, followed by Vc. Neither
      flavonoids had any systemic toxicity, even at 200 mg kg-1 body weight.
      Considering the low dose needed for protection and the high margin between the
      effective and toxic doses, the ocimum flavonoids may be promising for human
      radiation protection.

PMID- 9771391
TI  - Percutaneous placement of a self-expandable stent for treatment of a malignant
      pulmonary artery stenosis.
AB  - Venous stent placement is widely accepted as the treatment of stenoses caused by
      external tumour compression to reduced clinical sequelae. We report percutaneous
      stent placement into a severely obstructed right pulmonary artery in a 73-year
      old female patient. The underlying disease was a medistinal tumour mass of
      unknown aetiology. Pulmonary perfusion was successfully but temporarily restored
      by the intervention.

PMID- 9771392
TI  - The value of colour Doppler ultrasonography for small bowel involvement of adult
      Henoch-Schonlein purpura.
AB  - Three patients presented with a non-thrombocytopenic purpuric rash on their upper
      and lower limbs, abdominal pain, diarrhoea, and arthralgia. Grey scale ultrasound
      showed abnormally thickened walls of the small bowel. Colour Doppler showed blood
      flow signals in the diseased bowel wall in all patients. Subsequent barium and
      endoscopic studies showed oedematous bowel loops with petechial lesions. Biopsy
      from the purpuric rash of the skin demonstrated vasculitis of subdermal small
      vessels. The clinical diagnosis of Henoch-Schonlein purpura was made in each
      case. This paper describes the efficacy of grey scale and colour Doppler
      ultrasonography in the assessment of the small bowel involvement of Henoch
      Schonlein purpura.

PMID- 9771393
TI  - Mediastinal venous anomalies: potential pitfalls in cancer diagnosis.
AB  - Mediastinal venous anomalies encountered during CT assessments of cancer patients
      are often unsuspected and may be misinterpreted, particularly in the presence of
      intrathoracic disease. Errors in diagnosis result from a lack of intravenous
      contrast, concomitant mediastinal lymphadenopathy and primary intrathoracic
      tumour. The small calibre of vessels, previous mediastinal surgery and poor
      mediastinal planes are other confounding factors. An awareness of the anatomical
      features and optimal scanning technique are required to avoid misinterpretation.

PMID- 9771394
TI  - Case of the month. What a blow! Laryngocele.

PMID- 9771395
TI  - A perspective on the use of tubeless pancreatic function tests in diagnosis.

PMID- 9771396
TI  - Colonic embolisation: useful but caution required.

PMID- 9771397
TI  - Life (and death) in the Fas lane.

PMID- 9771398
TI  - Eradication of chronic Helicobacter pylori infection by therapeutic vaccination.
AB  - Chronic infection of the gastroduodenal mucosae by the gram-negative spiral
      bacterium Helicobacter pylori is responsible for chronic active gastritis, peptic
      ulcers, and gastric cancers such as adenocarcinoma and low-grade B-cell lymphoma.
      The success of eradication by antibiotic therapy is being rapidly hampered by the
      increasing occurrence of antibiotic-resistant strains. An attractive alternative
      approach to combat this infection is represented by the therapeutic use of
      vaccines. In the present work, we have exploited the mouse model of persistent
      infection by mouse-adapted H. pylori strains that we have developed to assess the
      feasibility of the therapeutic use of vaccines against infection. We report that
      an otherwise chronic H. pylori infection in mice can be successfully eradicated
      by intragastric vaccination with H. pylori antigens such as recombinant VacA and
      CagA, which were administered together with a genetically detoxified mutant of
      the heat-labile exterotoxin of Escherichia coli (referred to as LTK63), in which
      the serine in position 63 was replaced by a lysine. Moreover, we show that
      therapeutic vaccination confers efficacious protection against reinfection. These
      results represent strong evidence of the feasibility of therapeutic use of VacA-
      or CagA-based vaccine formulations against H. pylori infection in an animal model
      and give substantial preclinical support to the application of this kind of
      approach in human clinical trials.

PMID- 9771399
TI  - Effect of atropine on gastro-oesophageal reflux and transient lower oesophageal
      sphincter relaxations in patients with gastro-oesophageal reflux disease.
AB  - BACKGROUND: Atropine reduces the rate of reflux episodes in normal subjects by
      inhibition of transient lower oesophageal sphincter (LOS) relaxations. The aim of
      this study was to investigate the effect of atropine on the rate and mechanisms
      of reflux in patients with reflux disease. METHODS: Oesophageal motility and pH
      were recorded for one hour after a meal in 15 patients with reflux disease. On
      separate days, atropine (15 micrograms/kg bolus intravenously, 4 micrograms/kg/h
      infusion) or saline were given and maintained for the recording period. RESULTS:
      Atropine significantly reduced basal LOS pressure from 7.1 (2.2) to 2.9 (1.3) mm
      Hg (mean (SEM)). Atropine also reduced the rate of reflux episodes from 5.0 (2.0
      8.75) to 1.0 (0-6.25) per hour (median (interquartile range)) largely because of
      a decrease in the rate of transient LOS relaxations from 2.0 (0-4.75) to 0 (0-0)
      per hour and abolition of reflux during swallow induced LOS relaxation. There was
      no change in the rate of reflux episodes because of absent basal LOS pressure.
      CONCLUSIONS: Atropine inhibits reflux in patients with reflux disease largely by
      inhibition of transient LOS relaxations and swallow induced LOS relaxation. These
      findings suggest that pharmacological control of reflux through control of
      transient LOS relaxations is possible in patients with reflux disease.

PMID- 9771400
TI  - Intestinal metaplasia at the gastro-oesophageal junction: Helicobacter pylori
      gastritis or gastro-oesophageal reflux disease?
AB  - BACKGROUND: Intestinal metaplasia, whether in the cardia or the distal
      oesophagus, has been uniformly defined as specialised columnar epithelium,
      suggesting a relation with Barrett's oesophagus. It is, however, not clear
      whether the risk factors associated with intestinal metaplasia are identical at
      both sites. AIMS: To investigate biopsy specimens obtained below the
      squamocolumnar junction (SCJ) in relation to endoscopic aspect, gastric
      histology, and clinical presentation. PATIENTS AND METHODS: In 423 patients
      investigated the endoscopic aspect of the SCJ was classified as unremarkable
      (group I, n = 315) or suggestive of Barrett's oesophagus (group II, n = 108).
      Standardised biopsy specimens from the antrum, corpus, and directly below the SCJ
      were investigated. RESULTS: Intestinal metaplasia was detected at the SCJ in
      13.4% of group I patients, where it was significantly associated with gastric
      intestinal metaplasia (odds ratio (OR) 6.96; confidence interval (CI) 2.48 to
      19.54) and H pylori (OR 7.85; CI 2.82 to 21.85), and in 34.3% of group II
      patients where it was significantly associated with reflux symptoms (OR 19.98; CI
      6.12 to 65.19), erosive oesophagitis (OR 12.16; CI 3.86 to 38.24), and male sex
      (OR 6.25, CI 2.16 to 18.14), but not with H pylori or gastric intestinal
      metaplasia. CONCLUSION: This study suggests that the pathogenesis of intestinal
      metaplasia at the SCJ is not uniform: at an endoscopically unremarkable SCJ it is
      a sequela of H pylori gastritis, but coexisting with endoscopic features of
      Barrett's oesophagus it is associated with male sex and gastro-oesophageal reflux
      disease.

PMID- 9771401
TI  - Effect of sodium ion coupled nutrient transport on intestinal permeability in
      chronically catheterised rats.
AB  - BACKGROUND: The significance of Nanutrient cotransport induced alterations in
      paracellular permeability is controversial. Most previous studies have measured
      intestinal permeability using in vitro methods or in vivo methods immediately
      after surgical bowel manipulation, and therefore may not be applicable to normal
      physiological conditions. AIMS: To determine whether activation of Na coupled
      nutrient transport increases intestinal permeability under normal physiological
      conditions. METHODS: The effect of Na-nutrient cotransport on intestinal
      permeability was measured in unrestrained, unanaesthetised, chronically
      catheterised male Sprague-Dawley rats using two different methods: measurement of
      the rate of absorption of passively absorbed hexoses, mannitol and L-glucose; and
      measurement of the mannitol:urea diffusion ratio. RESULTS: L-Glucose and mannitol
      absorption were not increased in the presence of D-glucose, alanine, maltose, or
      peptides. The mannitol:urea diffusion ratio was not increased by the presence of
      D-glucose. The presence of D-glucose in the intestinal lumen for 20 minutes did
      not alter intestinal permeability. CONCLUSIONS: Under normal physiological
      conditions, Na coupled nutrient transport does not increase intestinal
      permeability.

PMID- 9771402
TI  - A simple clinical colitis activity index.
AB  - BACKGROUND: The appropriate medical treatment of patients with ulcerative colitis
      is determined largely by the severity of symptoms. Hospital assessment of the
      severity of disease activity includes investigation of laboratory indices and
      sigmoidoscopic assessment of mucosal inflammation. AIMS: To develop a simplified
      clinical colitis activity index to aid in the initial evaluation of exacerbations
      of colitis. METHODS: The information for development of the simple index was
      initially evaluated in 63 assessments of disease activity in patients with
      ulcerative colitis where disease activity was evaluated using the Powell-Tuck
      Index (which includes symptoms, physical signs, and sigmoidoscopic appearance).
      The new index was then further evaluated in 113 assessments in a different group
      of patients, by comparison with a complex index utilising clinical and laboratory
      data, as well as five haematological and biochemical markers of disease severity.
      RESULTS: The newly devised Simple Clinical Colitis Activity Index, consisting of
      scores for five clinical criteria, showed a highly significant correlation with
      the Powell-Tuck Index (r = 0.959, p < 0.0001) as well as the complex index (r =
      0.924, p < 0.0001) and all laboratory markers (p = 0.0003 to p < 0.0001).
      CONCLUSIONS: This new Simple Colitis Activity Index shows good correlation with
      existing more complex scoring systems and therefore could be useful in the
      initial assessment of patients with ulcerative colitis.

PMID- 9771403
TI  - Five genetic markers in the interleukin 1 family in relation to inflammatory
      bowel disease.
AB  - BACKGROUND: An imbalance between the proinflammatory cytokine interleukin 1 beta
      (IL-1 beta) and the anti-inflammatory cytokine IL-1 receptor antagonist (IL-1ra)
      has been postulated as a pathogenic factor in inflammatory bowel disease (IBD).
      AIMS: To study allelic frequencies of novel polymorphisms in the genes for IL-1
      beta and IL-1ra in patients with IBD and to assess the relation between ex vivo
      cytokine production and allelic variants of the IL-1 beta and IL-1ra genes.
      SUBJECTS: Two hundred and seventy healthy controls, 74 patients with ulcerative
      colitis (UC), 72 with Crohn's disease (CD), 40 with primary sclerosing
      cholangitis for the allelic frequencies, and 60 healthy individuals for the ex
      vivo stimulation test. METHODS: Genotyping was performed by polymerase chain
      reaction and subsequent cleavage with specific endonucleases (Mwo1, MspAI1, Alu1,
      Taq1, BsoF1) for five novel restriction fragment length polymorphisms (RFLPs) in
      the genes for IL-1ra and IL-1 beta. RESULTS: No significant differences were
      found in the allelic frequencies or allele carriage rates of the markers in the
      IL-1 beta and IL-1ra genes between CD, UC, and healthy controls. No association
      between the genetic markers and cytokine production levels was observed. Patients
      with UC carried the combination of both the infrequent allele of the Taq1 RFLP
      and the Mwo1 RFLP significantly more frequently (35.2% in UC versus 71.1% in
      controls). CONCLUSIONS: UC is associated with carriage of both infrequent alleles
      of the Taq1 and Mwo1 RFLPs. However, it could not be confirmed whether the
      association reflects a pathogenic mechanism underlying UC.

PMID- 9771404
TI  - Visualising E-selectin in the detection and evaluation of inflammatory bowel
      disease.
AB  - BACKGROUND: Vascular endothelial E-selectin expression is induced by
      proinflammatory cytokines and contributes to accumulation of leucocytes in
      tissues. AIMS: To investigate the role of E-selectin in inflammatory bowel
      disease (IBD). METHODS: E-selectin expression was assessed in patients with
      ulcerative colitis and Crohn's disease by measuring the concentration of
      circulating soluble E-selectin (sE-selectin) using ELISA, by immunohistochemistry
      of colonic biopsy specimens, and by abdominal immunoscintigraphy after injecting
      radiolabelled F(ab')2 fragment of a monoclonal anti-E-selectin antibody. The
      value of scintigraphy using anti-E-selectin was judged by a prospective
      comparative study of autologous leucocyte scanning and E-selectin antibody
      scanning in 17 patients with IBD. RESULTS: Circulating sE-selectin was elevated
      in patients with clinically active disease. Tissue expression of E-selectin was
      enhanced in patients with active inflammation, with weak or absent expression in
      inactive disease and healthy controls. In-111 labelled anti-E-selectin
      scintiscans were compared with Tc-99m labelled leucocyte scans performed 24 hours
      earlier. Twelve patients had areas of active inflammation on leucocyte scan while
      11 patients had positive E-selectin scans. The results of the two scans were
      concordant in 14 patients, with those positive for both (10/17) showing similar
      disease localisation and extent. CONCLUSIONS: Tissue E-selectin and circulating
      sE-selectin are increased during active inflammatory bowel disease. Anti-E
      selectin imaging with radiolabelled monoclonal antibody identified areas of
      inflammation in Crohn's disease and ulcerative colitis. The technique should
      prove useful clinically for identifying the site and extent of disease.

PMID- 9771405
TI  - High Fas ligand expression on lymphocytes in lesions of ulcerative colitis.
AB  - BACKGROUND: The pathogenesis of ulcerative colitis is unclear, but cytotoxic T
      lymphocytes infiltrating the mucosa have been implicated in mucosal damage. The
      Fas ligand (FasL), expressed on cytotoxic T lymphocytes, induces apoptosis in
      cells expressing Fas. AIM: To analyse FasL expression in affected colonic mucosa
      to ascertain Fas-FasL interaction in ulcerative colitis. METHODS: FasL mRNA was
      quantified in colonic mucosal specimens from healthy subjects and patients with
      ulcerative colitis or Crohn's disease, using the competitive reverse
      transcription polymerase chain reaction. FasL mRNA localisation was determined by
      in situ hybridisation. Expression of Fas in colonic mucosa was analysed
      immunohistochemically. Phenotypes of lamina propria lymphocytes that expressed
      FasL were analysed by flow cytometry. RESULTS: FasL mRNA was strongly expressed
      in active ulcerative colitis lesions, but not in those associated with active
      Crohn's disease or active proctitis-type ulcerative colitis. In situ
      hybridisation showed that FasL mRNA expression occurred in mononuclear cells
      infiltrating lesions. Fas was expressed in epithelial cells in ulcerative colitis
      and Crohn's disease, and in normal subjects. Cytometry showed that FasL was
      expressed in CD3 lymphocytes infiltrating the lamina propria in active lesions.
      CONCLUSIONS: FasL is expressed in CD3 lymphocytes infiltrating into ulcerative
      colitis but not Crohn's disease lesions, suggesting that Fas-FasL induced
      apoptosis participates in the mucosal damage of ulcerative colitis.

PMID- 9771406
TI  - Expression of inducible nitric oxide synthase activity in human colon epithelial
      cells: modulation by T lymphocyte derived cytokines.
AB  - BACKGROUND: Nitric oxide (NO) synthesis and inducible nitric oxide synthase
      (iNOS) expression are increased in colonic biopsy specimens from patients with
      ulcerative colitis, but the cellular source of NO production is not known. AIMS:
      To examine the distribution of iNOS in human colonic mucosa and to explore the
      ability of T lymphocyte derived cytokines to regulate iNOS expression and
      activity in human colonic epithelial cells. METHODS: iNOS expression was examined
      using immunohistochemistry in colonic biopsy samples from 12 patients with
      ulcerative colitis and three with infectious colitis and compared with 10 normal
      controls. In vitro iNOS expression and activity were determined in HT-29 cell
      cultures; nitrite levels were measured using a fluorescent substrate, iNOS mRNA
      expression by northern blot analysis, and iNOS protein expression by western blot
      analysis. RESULTS: No iNOS expression was detected (10 of 10) in non-inflamed
      mucosa derived from normal controls. In 11 of 12 cases of newly diagnosed
      ulcerative colitis, iNOS protein was expressed in the epithelial cells, while no
      other positive cells were found in the lamina propria. Similar iNOS labelling was
      found in colonic biopsy samples from patients with infectious colitis in the
      acute phase, but when re-examined in samples from patients in total remission, no
      iNOS staining was observed. Both interleukin (IL)-13 and IL-4, but not IL-10, are
      potent inhibitors of iNOS expression and activity induced by an optimal
      combination of cytokines, namely IL-1 alpha, tumour necrosis factor alpha and
      interferon gamma. CONCLUSIONS: The data suggest that the epithelium is the major
      source of iNOS activity in ulcerative colitis and that IL-13 and IL-4 may act as
      intrinsic regulators of NO generation in intestinal inflammation.

PMID- 9771407
TI  - Reduced susceptibility of mice overexpressing transforming growth factor alpha to
      dextran sodium sulphate induced colitis.
AB  - BACKGROUND: Transforming growth factor alpha (TGF-alpha) knockout mice have
      increased susceptibility to dextran sodium sulphate (DSS) induced colitis. AIM:
      To substantiate the findings that TGF-alpha is a key mediator of colonic mucosal
      protection and/or repair mechanisms by evaluating the susceptibility of mice
      overexpressing TGF-alpha to DSS induced colitis. METHODS: TGF-alpha
      overexpression was induced in transgenic mice by ZnSO4 administration in drinking
      water (TG+). Three groups were used as controls: one transgenic group without
      ZnSO4 administration (TG-), and two non-transgenic littermate groups receiving
      ZnSO4 (Non-TG+) or only water (Non-TG-). Acute colitis was induced in all groups
      by administration of DSS (5%, w/v) in drinking water for six days and libitum.
      RESULTS: About 35-39% of the entire colonic mucosa was destroyed in Non-TG-, Non
      TG+, and TG- animals compared with 9% in TG+ mice. the crypt damage score was
      18.7 (0.9), 18.2 (1.0), 18.9 (0.8), and 6.8 (1.5) (means (SEM)) in Non-TG-, Non
      TG+, TG-, and TG+ mice respectively. Mucin and bromodeoxyuridine staining were
      markedly enhanced in colons of TG+ mice compared with controls, indicating
      increased mucosal protection and regeneration. CONCLUSIONS: The significantly
      reduced susceptibility of mice overexpressing TGF-alpha to DSS further
      substantiates that endogenous TGF-alpha is a pivotal mediator of protection
      and/or healing mechanisms in the colon.

PMID- 9771409
TI  - Transcatheter coil embolotherapy: a safe and effective option for major colonic
      haemorrhage.
AB  - BACKGROUND: The management of major colonic bleeding is problematic. A proportion
      of patients require emergency surgery which is associated with high morbidity and
      mortality. Percutaneous embolotherapy, previously considered a high risk
      procedure in the colon, may provide an alternative treatment in this group of
      patients. AIMS: To assess the safety and efficacy of embolotherapy in the
      treatment of life threatening colonic haemorrhage. PATIENTS AND METHODS: Thirty
      eight patients with fresh haemorrhage per rectum were referred for surgery
      because of failed conservative treatment. All underwent angiography; in 14 a
      bleeding site or vascular abnormality was detected. A coaxial catheter was
      directed to the most distal bleeding artery and this was embolised with platinum
      coils. RESULTS: Detection of a bleeding site correlated with haemodynamic
      stability at the time of angiography (r = 1 for a systolic blood pressure less
      than 100 mm Hg). Bleeding sites or vascular abnormalities were detected and
      embolised in 14 patients (37%). In 12/14 there was immediate and sustained
      haemodynamic improvement; two continued to bleed and required emergency
      hemicolectomy (14%). Three developed ischaemic complications (21.4%); these were
      managed conservatively and required no intervention. The 30 day mortality was
      7.1% in the embolotherapy group and 10.5% in the overall group of 38 patients.
      CONCLUSION: Colonic embolotherapy for life threatening haemorrhage is an
      effective, relatively safe procedure with a low incidence of major complications.
      Its use depends on the identification of a focal bleeding point or vascular
      abnormality, which in turn depends on the haemodynamic stability of the patient
      at the time of angiography.

PMID- 9771408
TI  - Inflammatory bowel disease-like enteritis and caecitis in a senescence
      accelerated mouse P1/Yit strain.
AB  - BACKGROUND: A new subline of the senescence accelerated mouse (SAM) P1/Yit strain
      has been established which shows spontaneous enteric inflammation under specific
      pathogen free (SPF) conditions. AIMS: To elucidate the pathogenesis of enteric
      inflammation in this new subline. METHODS: The SPF and germ free (GF) SAMP1/Yit
      strains were used. Histological, immunological, and microbiological
      characterisation of the mice with enteric inflammation was performed. RESULTS:
      Histologically, enteritic inflammation developed as a discontinuous lesion in the
      terminal ileum and caecum with the infiltration of many inflammatory cells after
      10 weeks of age. the activity of myeloperoxidase, and both immunolocalisation and
      mRNA expression of inducible nitric oxide synthase increased in the lesion. CD3
      epsilon positive T cells, neutrophils, and macrophages were more numerous in the
      inflamed mucosa of the SAMP1/Yit strain. The GF SAMP1/Yit strain did not show any
      inflammation in the intestinal wall, by the age of 30 weeks, and the enteritis
      and caecitis developed 10 weeks after the conventionalisation of the GF SAMP1/Yit
      strain. CONCLUSION: Enteric inflammation in the ileum and caecum developed in the
      SAMP1/Yit strain. The pathophysiological characteristics of the disease in this
      mouse have some similarities to those of human inflammatory bowel disease (IBD).
      This mouse strain should be a useful model system for elucidating the interaction
      between the pathogenesis of IBD and the gut microflora.

PMID- 9771410
TI  - Colonic epithelial cell proliferation in hereditary non-polyposis colorectal
      cancer.
AB  - BACKGROUND: Despite the recent discovery of four genes responsible for up to 90%
      of all cases of hereditary non-polyposis colorectal cancer (HNPCC), there will
      still be families in whom predictive testing is not possible. A phenotypic
      biomarker would therefore be useful. An upwards shift of the proliferative
      compartment in colonic crypts is reported to be one of the earliest changes in
      premalignant mucosa. AIMS: To assess the role of crypt cell proliferation as a
      phenotypic biomarker in HNPCC. PATIENTS: Thirty five patients at 50% risk of
      carrying the HNPCC gene (21 of whom subsequently underwent predictive testing and
      hence gene carrier status was known) and 18 controls. METHODS: Crypt cell
      proliferation was measured at five sites in the colon using two different
      techniques. Labelling index was determined using the monoclonal antibody MIB1 and
      whole crypt mitotic index was measured using the microdissection and crypt squash
      technique. The distribution of proliferating cells within the crypts was also
      assessed. RESULTS: There were no significant differences in the total labelling
      index or mean number of mitoses per crypt, nor in the distribution of
      proliferating cells within the crypt, between the study and control groups at any
      site. When the 21 patients in whom gene carrier status was known were analysed
      separately there were no significant differences in the measured indices of
      proliferation between the HNPCC gene carriers and non-gene carriers. CONCLUSION:
      Crypt cell proliferation is not a discriminative marker of gene carriage in
      HNPCC.

PMID- 9771411
TI  - Folate depletion impairs DNA excision repair in the colon of the rat.
AB  - BACKGROUND/AIMS: Diminished folate status appears to promote colonic
      carcinogenesis by, as of yet, undefined mechanisms. Impaired DNA repair plays a
      significant role in the evolution of many colon cancers. Since folate is
      essential for the de novo synthesis of nucleotides and since folate depletion has
      previously been associated with excessive DNA strand breaks, it was hypothesised
      that folate depletion may impair DNA repair. Studies were therefore performed to
      examine whether folate depletion affects the two major categories of DNA repair.
      METHODS: Study 1: eight weanling male Sprague-Dawley rats were fed on diets
      containing either 0 or 8 mg folate/kg diet with 1% succinylsulphathiazole for
      four weeks. After viable colonocytes had been harvested, DNA excision repair was
      evaluated by a single cell gel electrophoresis assay. Study 2: eighteen animals
      were fed on similar diets for five weeks. Also in study 2, 18 additional rats
      were fed on the same defined diet without succinylsulphathiazole for 15 weeks.
      Weekly injections with the procarcinogen, 1,2-dimethylhydrazine (20 mg base/kg),
      were administered to the latter group of animals. Five microsatellite loci from
      different chromosomes were investigated for instability in hepatic and colonic
      DNA. RESULTS: In study 1, a significantly retarded rate of DNA excision repair
      was observed in the folate deficient colonocytes compared with controls (p <
      0.05). In study 2, there was no evidence of instability at the five
      microsatellite loci associated with either short or long term folate depletion.
      CONCLUSIONS: Folate deficiency impairs DNA excision repair in rat colonic mucosa;
      a similar degree of deficiency, even when administered in conjunction with a
      colonic carcinogen, did not produce evidence of a widespread defect in mismatch
      repair.

PMID- 9771412
TI  - Identification of gases responsible for the odour of human flatus and evaluation
      of a device purported to reduce this odour.
AB  - BACKGROUND/AIMS: While the social significance of flatus derives mainly from its
      odour, previous studies have focused on the non-odoriferous components of rectal
      gas. The aims of the present study were to determine the role of sulphur
      containing gases in flatus odour and test the efficacy of a device purported to
      reduce this odour. METHODS: Flatus was quantitatively collected via rectal tube
      from 16 healthy subjects who ingested pinto beans and lactulose to enhance flatus
      output. The concentrations of sulphur-containing gases in each passage were
      correlated with odour intensity assessed by two judges. Odour intensity was also
      determined after treatment of flatus samples with zinc acetate, which binds
      sulphydryl compounds (hydrogen sulphide and methanethiol), or activated charcoal.
      Utilising gastight Mylar pantaloons, the ability of a charcoal lined cushion to
      adsorb sulphur-containing gases instilled at the anus of eight subjects was
      assessed. RESULTS: The main sulphur-containing flatus component was hydrogen
      sulphide (1.06 (0.2) mumol/l), followed by methanethiol (0.21 (0.04) mumol/l) and
      dimethyl sulphide (0.08 (0.01) mumol/l) (means (SEM)). Malodour significantly
      correlated with hydrogen sulphide concentration (p < or = 0.001). Zinc acetate
      reduced sulphur gas content but did not totally eliminate odour, while activated
      charcoal removed virtually all odour. The cushion absorbed more than 90% of the
      sulphur gases. CONCLUSION: Sulphur-containing gases are the major, but not the
      only, malodorous components of human flatus. The charcoal lined cushion
      effectively limits the escape of these sulphur-containing gases into the
      environment.

PMID- 9771413
TI  - Non-cardiac, non-oesophageal chest pain: the relevance of psychological factors.
AB  - BACKGROUND: No cause has been determined for chest pain that is neither cardiac
      nor oesophageal in origin. AIMS: To compare the prevalence of life-time
      psychiatric disorders and current psychological distress in three consecutive
      series of patients with chronic chest or abdominal pain. PATIENTS: Thirty nine
      patients with non-cardiac chest pain and no abnormality on
      oesophagogastroduodenoscopy, oesophageal manometry, and 24 hour pH monitoring; 22
      patients with non-cardiac chest pain having endoscopic abnormality, oesophageal
      dysmotility, and/or pathological reflux; and 36 patients with biliary colic.
      METHODS: The Diagnostic Interview Schedule and the 28 item General Health
      Questionnaire were administered to all patients. RESULTS: Patients with non
      cardiac chest pain and no upper gastrointestinal disease had a higher proportion
      of panic disorder (15%), obsessive-compulsive disorder (21%), and major
      depressive episodes (28%) than patients with gallstone disease (0%, p < 0.02; 3%,
      p < 0.02; and 8%, p < 0.05, respectively). In contrast, there were no differences
      between patients with non-cardiac chest pain and upper gastrointestinal disease
      and patients with gallstone disease in any of the DSM-111 defined lifetime
      psychiatric diagnoses. Using the General Health Questionnaire, 49% of patients
      with non-cardiac chest pain without upper gastrointestinal disease scored above
      the cut off point (that is, more than 4), which was considered indicative of non
      psychotic psychiatric disturbance, whereas only 14% of patients with gallstones
      did so (p < 0.005). The proportions of such cases were however similar between
      patients with non-cardiac chest pain and upper gastrointestinal disease (27%) and
      patients with gallstones. CONCLUSIONS: Psychological factors may play a role in
      the pathogenesis of chest pain that is neither cardiac nor oesophagogastric in
      origin.

PMID- 9771414
TI  - Lipids infused into the jejunum accelerate small intestinal transit but delay
      ileocolonic transit of solids and liquids.
AB  - BACKGROUND: Various nutrients are known to alter small intestinal motility
      patterns although their effect on transit of fluids and solids in man is not
      clear. AIMS: To determine small intestinal transit of solids and liquids during
      perfusion with lipids, protein, and non-energy solutions. METHODS: Twenty eight
      healthy volunteers received a jejunal infusion (1 ml/minute for 30 minutes) of
      one of four solutions: a lipid or a protein solution (4.18 J/ml), a non
      absorbable electrolyte solution containing polyethylene glycol, or 0.9% sodium
      chloride. As solid phase marker 1 g of amberlite resin pellets labelled with
      111InCl3 was added; 99mTc DTPA was used as a fluid phase marker. Images were
      obtained on a gamma camera at 10 minute intervals for four hours or until all
      radiolabel was detected in the colon. RESULTS: Intestinal transit of solids and
      liquids from the duodenojejunal junction to the caecum was simultaneous, and
      independent of the energy content of the solution infused. Lipid infusion
      accelerated transit through the small intestine but delayed transport of chyme
      along the ileocolonic junction. After protein small intestinal transit was
      slowest; ileocolonic transit on the other hand was fastest with protein. Transit
      of the non-energy solutions was in between that of the nutrient solutions.
      CONCLUSIONS: Transit times through the small intestine and the ileocolonic
      junction were influenced by the luminal contents. In the small intestine fat
      induced significantly faster transit compared with proteins, but delayed
      ileocolonic transit. Once in the small intestine, solids and liquids transit the
      small bowel together, independent of the luminal content.

PMID- 9771415
TI  - Chronic intestinal pseudo-obstruction in systemic lupus erythematosus.
AB  - BACKGROUND/AIMS: Chronic intestinal pseudo-obstruction (CIPO) reflects a
      dysfunction of the visceral smooth muscle or the enteric nervous system.
      Gastrointestinal manifestations are common in systemic lupus erythematosus (SLE)
      but CIPO has not been reported. Features of CIPO are reported in five patients
      with SLE. METHODS: From 1988 to 1993, five patients with SLE or SLE-like syndrome
      were hospitalised for gastrointestinal manometric studies. CIPO was the onset
      feature in two cases. Antroduodenal manometry (three hours fasting, two hours
      fed) was performed in all patients, and oesophageal manometry in four. RESULTS:
      Intestinal hypomotility associated with reduced bladder capacity and bilateral
      ureteral distension was found in four patients and aperistalsis of the oesophagus
      in three. Treatment, which consisted of high dose corticosteroids, parenteral
      nutrition, promotility agents, and antibiotics, led to remission of both CIPO and
      urinary abnormalities in all cases. Antroduodenal manometry performed in two
      patients after remission showed increased intestinal motility. One patient died,
      and postmortem examination showed intestinal vasculitis. CONCLUSIONS: CIPO in SLE
      is a life threatening situation that can be reversed by treatment. It may be: (a)
      a complication or onset feature of the disease; (b) secondary to smooth muscle
      involvement; (c) associated with ureteral and vesical involvement; (d) the result
      of intestinal vasculitis.

PMID- 9771416
TI  - Acute effects of therapeutic irradiation for prostatic carcinoma on anorectal
      function.
AB  - AIM: The incidence of anorectal symptoms after radiotherapy (RTH) for localised
      pelvic malignant disease is unclear. In addition, the effects of pelvic
      irradiation on both anorectal motility and sensory function are poorly defined. A
      prospective study was therefore performed on 35 patients (55-82 years of age)
      with localised prostatic carcinoma before and four to six weeks after RTH to
      assess its effects on anorectal function. METHODS: Anorectal symptoms were
      assessed by questionnaire. Anorectal pressures at rest and in response to
      voluntary squeeze, rectal distension, and increases in intra-abdominal pressure
      were evaluated with perfused sleeve side hole manometry. Rectal sensation was
      tested during graded balloon distension. Rectal compliance was calculated by the
      pressure-volume relation obtained during the testing of rectal sensation.
      Ultrasound was used to determine anal sphincter structure and integrity. RESULTS:
      RTH had no effect on anal sphincter morphology. The frequency of defecation
      increased after RTH (7 (3-21) v 10 (3-56) bowel actions a week; p < 0.01). After
      RTH, 16 patients had faecal urgency and eight faecal incontinence, compared with
      five and one respectively before RTH (p < 0.01 for each). Basal and squeeze
      sleeve recorded pressures were reduced after RTH (54 (3) v 49 (3) mm Hg (p <
      0.05) and 111 (8) v 102 (8) mm Hg (p < 0.01), before and after RTH respectively;
      means (SEM)). Rectal compliance was reduced after RTH (1.2 v 1.4 mm Hg/ml, p <
      0.05). After RTH, threshold volumes for perception of rectal distension were
      lower in the 16 patients who either experienced faecal urgency for the first time
      (13 patients) or reported worsening of this symptom (three patients) compared
      with the remaining patients (34 (4) v 48 (5) ml respectively, p < 0.05).
      CONCLUSION: Faecal incontinence (23%) is a common problem four to six weeks after
      RTH for prostatic carcinoma and is associated with minor reductions in anal
      sphincter pressures. The high prevalence of faecal urgency in patients after RTH
      may be related to alterations in rectal perception of stool.

PMID- 9771417
TI  - Periacinar stellate shaped cells in rat pancreas: identification, isolation, and
      culture.
AB  - BACKGROUND: The pathogenesis of pancreatic fibrosis is unknown. In the liver,
      stellate cells (vitamin A storing cells) play a significant role in the
      development of fibrosis. AIMS: To determine whether cells resembling hepatic
      stellate cells are present in rat pancreas, and if so, to compare their number
      with the number of stellate cells in the liver, and isolate and culture these
      cells from rat pancreas. METHODS: Liver and pancreatic sections from chow fed
      rats were immunostained for desmin, glial fibrillary acidic protein (GFAP), and
      alpha smooth muscle actin (alpha-SMA). Pancreatic stellate shaped cells were
      isolated using a Nycodenz gradient, cultured on plastic, and examined by phase
      contrast and fluorescence microscopy, and by immunostaining for desmin, GFAP, and
      alpha-SMA. RESULTS: In both liver and pancreatic sections, stellate shaped cells
      were observed; these were positive for desmin and GFAP and negative for alpha
      SMA. Pancreatic stellate shaped cells had a periacinar distribution. They
      comprised 3.99% of all pancreatic cells; hepatic stellate cells comprised 7.94%
      of all hepatic cells. The stellate shaped cells from rat pancreas grew readily in
      culture. Cells cultured for 24 hours had an angular appearance, contained lipid
      droplets manifesting positive vitamin A autofluorescence, and stained positively
      for desmin but negatively for alpha-SMA. At 48 hours, cells were positive for
      alpha-SMA. CONCLUSIONS: Cells resembling hepatic stellate cells are present in
      rat pancreas in a number comparable with that of stellate cells in the liver.
      These stellate shaped pancreatic cells can be isolated and cultured in vitro.

PMID- 9771418
TI  - Enhanced fibroblast growth factor 5 expression in stromal and exocrine elements
      of the pancreas in chronic pancreatitis.
AB  - BACKGROUND: Fibroblast growth factor 5 (FGF-5) belongs to a group of mitogenic
      and angiogenic heparin binding growth factors but its potential role in chronic
      inflammatory conditions is not known. AIMS: To compare FGF-5 expression in the
      normal pancreas and in the pancreas of patients with chronic pancreatitis (CP)
      and to characterise FGF-5 expression and secretion in TAKA-1 cells, an
      immortalised Syrian hamster pancreatic duct cell line. METHODS AND RESULTS:
      Northern blotting revealed the presence of a 4.0 kb FGF-5 mRNA transcript in both
      normal and CP tissue samples. Densitometric analysis indicated that the
      transcript levels were increased by a factor of 1.44 in CP tissue samples
      compared with normal tissue samples (p = 0.039). By immunohistochemisty and in
      situ hybridisation, FGF-5 was faintly expressed in ductal and islet cells in the
      normal pancreas. In contrast, in CP tissue samples, there was abundant expression
      of FGF-5 in ductal, acinar, and islet cells, as well as in periductal
      fibroblasts. FGF-5 was also expressed in TAKA-1 cells as determined by Northern
      blotting. By immunoblotting of heparinsepharose precipitates, TAKA-1 cells were
      shown to secrete FGF-5 into the medium. CONCLUSION: Exocrine and stromal derived
      FGF-5 has the potential to participate in autocrine and paracrine pathways that
      may contribute to the pathobiology of chronic pancreatitis.

PMID- 9771419
TI  - Patterns of alcohol consumption after liver transplantation.
AB  - BACKGROUND: Uncertainty exists about the extent and consequences of a return to
      alcohol consumption after liver transplantation for alcoholic liver disease
      (ALD). AIMS: To determine the prevalence and consequences of alcohol consumption
      in patients transplanted for ALD. METHODS: A retrospective case controlled study
      of all patients transplanted for ALD at the Queen Elizabeth Hospital, Birmingham,
      between 1987 and 1996. RESULTS: Seventy patients with ALD were transplanted, of
      which 59 survived more than three months; 56 were interviewed. Twenty eight had
      consumed some alcohol after transplantation; for the nine "heavy drinkers" (HD),
      the median time to resumption of alcohol intake was six months and for the 19
      "moderate drinkers" (MD) it was eight months. There was no significant difference
      in episodes of acute rejection or compliance with medication between those who
      were abstinent, MD, or HD. Histological evidence of liver injury was common in
      ALD patients who had returned to drink. Mild fatty change was found in 1/11
      biopsy specimens from abstinent patients but moderate to severe fatty change and
      ballooned hepatocytes were seen in 3/5 MD and 2/5 HD specimens. Two HD patients
      had early fibrosis. One HD patient had died of alcohol related complications.
      CONCLUSIONS: Moderate to heavy alcohol consumption occurs in patients
      transplanted for ALD. Patient recall of abstinence advice is unreliable, and
      patients return to alcohol mainly within the first year after liver
      transplantation. Return to alcohol consumption after liver transplantation is
      associated with rapid development of histological liver injury including
      fibrosis.

PMID- 9771420
TI  - Gall bladder motility after endoscopic sphincterotomy.

PMID- 9771421
TI  - Specificity of small bowel biopsy findings in coeliac disease.

PMID- 9771422
TI  - Prevalence of the factor V Leiden mutation in portal and hepatic vein thrombosis.

PMID- 9771423
TI  - Steatorrhoea and pancreatic disease in HIV infected patients.

PMID- 9771424
TI  - Treatment of Helicobacter pylori infection.

PMID- 9771425
TI  - One week triple therapy for Helicobacter pylori.

PMID- 9771426
TI  - Finance. Sluggish stocks.

PMID- 9771427
TI  - Medicaid. Providers make plans.

PMID- 9771428
TI  - Checkup 2020.
AB  - Step into tomorrow's consumer society, where tracking your health status goes
      hand in hand with brushing your teeth. In fact, 20 years from now, a visit to the
      doctor may be no further than your bathroom.

PMID- 9771429
TI  - Rural route delivery.
AB  - When it comes to health insurance, Midwesterners are generally covered. What many
      rural communities lack is access to care. An Iowa hospital makes sure that
      patients in its region get where they need to go.

PMID- 9771430
TI  - Banking on bonuses.
AB  - Performance incentives cover a wider--and deeper--swath of health care than ever,
      according to the latest Hay Group surveys. Yet it's clear that most organizations
      are homegrowing compensation strategies that blend base and incentive pay into a
      cohesive package.

PMID- 9771431
TI  - Wall Street smart, Main Street savvy.

PMID- 9771432
TI  - Medicare+Choice. A windfall without the risks.

PMID- 9771433
TI  - Premium hikes. An open--and shut--contract.

PMID- 9771434
TI  - Hospital construction. Easy-does-it design.

PMID- 9771436
TI  - Is the practice of haematology evidence based? II. Evidence based morphological
      diagnosis.

PMID- 9771435
TI  - Effects of nerve growth factor (NGF) and other fibroblast-derived growth factors
      on immature human mast cells (HMC-1).
AB  - We have previously shown that fibroblast and keratinocyte supernatants up
      regulate expression of mast cell characteristics in the human immature mast cell
      line HMC-1. This effect could not be induced in HMC-1 cells by the well-known
      mast cell growth factor stem cell factor (SCF), probably due to mutations of the
      SCF receptor c-Kit in these cells. Here we report the effects of several known
      fibroblast- and keratinocyte-derived growth factors, namely nerve growth factor
      (NGF), basic fibroblast growth factor, platelet-derived growth factor and
      transforming growth factor-beta, on mast cell differentiation, using HMC-1 cells
      as a model. NGF, at 0.1-50 ng/ml concentrations, caused a marked, dose-dependent
      up-regulation of tryptase, Fc epsilon RI and histamine within 10 days of culture,
      associated with an enhanced expression of mRNA for Fc epsilon RI and mast cell
      tryptase. On restriction analysis, only mast cell beta-tryptase, but not alpha
      tryptase, could be demonstrated. Furthermore, the high-affinity NGF receptor
      (TrkA) was found at both the transcriptional and protein levels, while expression
      of the low-affinity NGF receptor was detectable at the mRNA level only. None of
      the other growth factors caused a significant alteration of the mast cell markers
      studied when added to HMC-1 cells at concentrations known to be biologically
      active in other culture systems. Immature human mast cells are thus induced to
      assume a more mature phenotype in vitro in response to NGF, most probably via
      stimulation of the high-affinity NGF receptor expressed on these cells. Besides
      SCF, NGF should therefore be considered as an additional mast cell growth factor
      that contributes to human mast cell maturation at tissue sites.

PMID- 9771437
TI  - Sudden infant death syndrome (SIDS): the search for the cause.

PMID- 9771438
TI  - Classification of acute leukaemia: the need to incorporate cytogenetic and
      molecular genetic information.

PMID- 9771440
TI  - Endothelial nitric oxide synthase immunoreactivity in early gestation and in
      trophoblastic disease.
AB  - AIMS: To study the localisation of the endothelial nitric oxide synthase (eNOS)
      in the normal placenta, with special emphasis on the implantation site in the
      first trimester of pregnancy, and in the different subtypes of trophoblastic
      cells in gestational trophoblastic disease. METHODS: The immunoperoxidase
      technique with an antibody directed against eNOS was applied to paraffin sections
      from first and second trimester placentas, placenta accreta, partial and complete
      hydatidiform moles, and choriocarcinoma. Immunoperoxidase staining for human
      placental lactogen (hPL) was performed on parallel sections. RESULTS: Prominent
      immunoreactivity for eNOS was found to be present in the intermediate
      trophoblastic cells of the cell columns of the anchoring villi and in
      trophoblastic cells at the implantation site. Staining was also present in the
      syncytiotrophoblast, most conspicuous at the apical cell border. In trophoblastic
      disease, proliferating large mononuclear cells, which were strongly positive for
      hPL, were found to be immunoreactive for eNOS. CONCLUSIONS: eNOS immunoreactivity
      is strongly positive in the extravillous trophoblastic cells and to a lesser
      extent in the syncytiotrophoblast. In the former it may play a role in
      implantation and vascular invasion. Cells with differentiation to intermediate
      trophoblast in complete hydatidiform mole and choriocarcinoma also show high
      levels of eNOS, which may be associated with the haematogenous mode of spread of
      trophoblastic disease.

PMID- 9771439
TI  - Vitamin K and metabolic bone disease.

PMID- 9771442
TI  - Interphase cytogenetic and AgNOR analyses of hydatidiform moles.
AB  - AIM: To determine the potential value of interphase cytogenetic and argyrophilic
      nucleolar organiser region (AgNOR) analyses in the diagnosis and classification
      of hydatidiform moles. METHODS: Serial tissue sections from 37 hydatidiform
      moles, histologically classified as 11 complete and 15 partial, and from 11
      hydropic abortuses were examined by in situ hybridisation using digoxigenin
      labelled probes specific for chromosomes 1, X, and Y, and a one step silver
      staining method. The percentages of diploid and triploid nuclei, and the mean
      number of AgNORs for each tissue were determined. RESULTS: Interphase
      cytogenetics showed that eight of the 11 cases (73%) each of complete mole and
      hydropic abortus had diploid pattern and the three remaining cases (27%) of each
      group were triploid. Two of the triploid complete moles and one of the triploid
      hydropic abortuses were revised to partial moles and one remaining triploid
      complete mole was revised to hydropic abortus. Of the 15 partial moles, nine
      (60%) were triploid, and six (40%) were diploid. These diploid cases were revised
      to three complete moles and three hydropic abortuses. There was a significant
      difference (p < 0.0001) between the mean (SD) AgNOR count in partial mole (5.11
      (0.91)) versus hydropic abortus (3.79 (0.90)) and complete mole (3.39 (0.97)).
      The total of 15 triploid cases showed a high mean AgNOR count of 5.24 (0.73).
      Also, after reclassification, eight of the nine partial moles (89%) had a mean
      AgNOR count of > or = 5. The results of analyses by the two methods were closely
      correlated. CONCLUSIONS: Interphasecytogeneticanalysis using chromosome specific
      probes and AgNOR count provides a valuable approach for ploidy analysis in
      histological sections of hydatidiform moles and helps to resolve difficult cases.

PMID- 9771441
TI  - Immunophenotypic and genotypic characterisation of multiple myelomas with adverse
      prognosis characterised by immunohistological expression of the T cell related
      antigen CD45RO (UCHL-1).
AB  - AIMS: To investigate whether plasma cell expression of early B cell, late B
      cell/preplasma cell, T cell, and myelomonocytic antigens or myeloma associated
      lymphocytic infiltrates correlated with prognosis in bone marrow biopsy specimens
      of patients with multiple myeloma. METHODS: Bone marrow biopsy specimens of 23
      patients with multiple myeloma were investigated for plasma cell expression and
      interstitial lymphocyte expression of T cell related antigen CD45RO (UCHL-1).
      RESULTS: Eight patients showed plasma cell expression of CD45RO and 16 showed
      increased tumour infiltrating CD45RO positive lymphocytes, which were correlated
      with poor survival by multivariate analyses (p = 0.005 and p = 0.04,
      respectively). B cell antigens (MB2, CD20) but no T cell specific antigens (CD3)
      or T cell receptor gene rearrangements were expressed by plasma cells in CD45RO
      positive myelomas. Of 16 patients with myeloma who had increased tumour
      infiltrating CD45RO positive lymphocytes, four had interstitial lymphocyte
      expression of B cell antigens and two had interstitial lymphocyte expression of
      the T cell specific antigen CD3. CONCLUSIONS: The recognition of plasma cell
      expression of CD45RO and increased interstitial CD45RO lymphocytes in bone marrow
      biopsy specimens of patients with multiple myeloma is an adverse prognostic
      finding not indicative of an aberrant T cell phenotype or genotype; it is
      consistent with B cell/pre-plasma cell antigen expression by myeloma cells and
      their lymphocytic precursors.

PMID- 9771443
TI  - In situ localisation of Yersinia enterocolitica by catalysed reported deposition
      signal amplification.
AB  - AIM: The sensitive detection of pathogenic Yersinia enterocolitica in paraffin
      embedded tissue sections by in situ hybridisation (ISH). METHODS: Y
      enterocolitica infected cell lines, rat spleens, and patient biopsy specimens
      were used to compare conventional ISH, immune fluorescence assay (IFA) detection,
      and catalysed reporter deposition (CARD) signal amplification ISH. RESULTS: CARD
      ISH was shown to be more sensitive then conventional ISH and had a comparable
      sensitivity to IFA. In contrast to IFA, CARD-ISH preserved good tissue
      morphology. CONCLUSIONS: CARD-ISH appeared to be a fast and sensitive ISH method
      for detecting Y enterocolitica in routinely processed tissue sections.
      Application of this method allows the combination of routine detection and
      cellular localisation of the pathogen within the infected tissue.

PMID- 9771444
TI  - Reproducibility of new classification schemes for the pathology of ductal
      carcinoma in situ of the breast.
AB  - AIM: To compare the interobserver variation in the pathological classification of
      ductal carcinoma in situ of the breast using two recently proposed classification
      schemes. METHODS: 11 pathologists classified a set of 25 cases of ductal
      carcinoma in situ chosen to reflect a range of lesions, using the traditional
      architectural classification together with the modified cytonuclear grading
      scheme of Holland et al and the Van Nuys classification scheme. Participating
      pathologists received a standard tutorial, written information, and illustrative
      photomicrographs before their assessment of the cases. RESULTS: Interobserver
      agreement was poorest when using the architectural scheme (kappa = 0.44), largely
      owing to variations in classifying lesions with a mixed component of patterns
      (kappa = 0.13). Agreement was better using the modified cytonuclear grading
      scheme (kappa = 0.57), with most consistency achieved using the Van Nuys scheme
      (kappa = 0.66). Most discordant results using the later scheme were due to
      inconsistency in assessing the presence or absence of luminal necrosis.
      CONCLUSIONS: Both the new classification schemes assessed in this study were an
      improvement over the traditional architectural classification system for ductal
      carcinoma in situ, and resulted in more reproducible pathological assignment of
      cases. The Van Nuys classification scheme is easy to apply, even to small areas
      of carcinoma, resulting in acceptable interobserver agreement between reporting
      pathologists. Additional work will be required to arrive at a consensus
      definition of necrosis for cases in the non-high-grade group.

PMID- 9771446
TI  - Prothrombin time derived fibrinogen determination on Sysmex CA-6000.
AB  - AIM: To evaluate PT derived fibrinogen determinations with reference to the
      Clauss fibrinogen assay using a Sysmex CA-6000 random access coagulation
      analyser. METHODS: Samples were analysed from normal subjects (n = 20), patients
      with renal or liver dysfunction (n = 25), critically ill patients (n = 25),
      patients receiving oral anticoagulant treatment (n = 50), and patients with a
      haemoglobinopathy (n = 127). Prothrombin times were performed using two
      thromboplastins: one derived from rabbit brain (Dade: Thromboplastin IS) and the
      other from recombinant human tissue factor (Dade: Innovin). Fibrinogen was
      assayed by the Clauss method using a commercial kit (Dade: Fibrinogen). RESULTS:
      The relation between Clauss fibrinogen and PT derived fibrinogen was found to be
      dependent on the patient's clinical group and source of the thromboplastin used.
      When the data from the above sample groups were pooled there was still a
      significant difference (p < 0.001) between Clauss fibrinogen and PT derived
      fibrinogen, irrespective of thromboplastin used. CONCLUSIONS: It is unsafe to use
      the PT derived fibrinogen for patient monitoring owing to non-uniform variability
      in response to clinical status and reagent employed; however, it may prove to be
      a useful screening test in a research environment for estimating fibrinogen
      levels among defined patient groups.

PMID- 9771445
TI  - Multivariate analyses of DNA index, p62c-myc, and clinicopathological status of
      patients with ovarian cancer.
AB  - AIM: To determine if either DNA index or p62c-myc is an independent prognostic
      variable in ovarian cancer. METHODS: Multivariate and univariate analyses of the
      relation between DNA index, p62c-myc, FIGO stage, histological type, tumour
      grade, completeness of surgery, and patient survival in ovarian cancer were
      examined. RESULTS: Multivariate analysis showed significant association of
      survival only with stage and grade. There was no relation between survival and
      DNA index. CONCLUSIONS: DNA index is not an independent prognostic variable in
      ovarian cancer.

PMID- 9771447
TI  - Haemoglobin Le Lamentin (alpha 20 (B1) His-->Gln) in a British family:
      identification by electrospray mass spectrometry.
AB  - The first identification of haemoglobin Le Lamentin (alpha 20 (B1) His-->Gln) in
      a British patient is described. The patient was a 69 year old asymptomatic white
      male being screened for diabetes, whose blood was undergoing its first ever
      analysis for glycated haemoglobin using a Glycomat II analyser. Identification of
      the haemoglobin variant was by electrospray mass spectrometry.

PMID- 9771448
TI  - Disappointing dipstick screening for urinary tract infection in hospital
      inpatients.
AB  - AIM: To compare the performance of leucocyte esterase and nitrite dipstick tests
      with microscopic examination and culture of first morning urines (n = 420) of
      hospital inpatients. RESULTS: The sensitivity, specificity, and negative
      predictive value of the leucocyte esterase test for the cutoff of > 10
      WBC/microliter were 57%, 94%, and 68%, respectively. For > 5 WBC per high power
      field (HPF) these variables were 84%, 90%, and 93%. For > 10(5) colony counts/ml,
      the sensitivity of the nitrite test was 27%, specificity 94%, and negative
      predictive value 87%. When either leucocyte esterase or nitrite positivity was
      accepted as a marker of urinary tract infection, the sensitivity was 78%,
      specificity 75%, and negative predictive value 94%, and there were 22% false
      negative results. Semiquantitative microscopic estimation of bacteria per HPF
      yielded 40% false positives. CONCLUSIONS: Leucocyte esterase and nitrite dipstick
      tests are not suitable for screening for urinary tract infections.

PMID- 9771450
TI  - Cytomegalovirus colitis in immunocompetent individual.
AB  - A woman with peripheral vascular disease developed cytomegalovirus colitis
      following repair of abdominal aortic aneurysm. Cytomegalovirus colitis developing
      in an immunocompetent individual may be caused by a breach in the integrity of
      the mucosal lining of the colon from various causes and should alert the
      clinician to explore these causes in order to provide effective care.

PMID- 9771449
TI  - A prospective controlled study of the association of Streptococcus bovis with
      colorectal carcinoma.
AB  - AIM: To investigate the ability of Streptococcus bovis to colonise colorectal
      cancers. PATIENTS: 19 patients with colorectal cancer and 23 controls without
      malignancy. SETTING: University teaching hospital. METHODS: Prospective study
      comparing unselected patients with known colorectal cancer with age and sex
      matched controls. Carcinoma tissue from patients with colorectal cancer and
      normal colonic mucosa, stool, and blood from both patients and control subjects
      were cultured. RESULTS: In contrast to published data, the faecal carriage rate
      was similar in cancer (11%) and control groups (13%). CONCLUSIONS: Faecal
      colonisation by Str bovis in colorectal cancer patients is lower than previously
      reported and does not differ significantly from controls.

PMID- 9771451
TI  - Cytokeratin expression in adrenal phaeochromocytomas and extra-adrenal
      paragangliomas.
AB  - AIM: To examine whether adrenal phaeochromocytomas and extra-adrenal
      paragangliomas are immunoreactive for commercially available and routinely used
      cytokeratin antibodies. METHODS: 18 extra-adrenal paragangliomas and seven
      adrenal phaeochromocytomas were stained with CAM 5.2, AE1/3, and 34 beta E12
      following microwave antigen retrieval of formalin fixed tissue. RESULTS: A single
      case from the cauda equina was positive for both CAM 5.2 and AE1/3. In addition,
      two other cases--an intravagal and an orbital paraganglioma--also showed strong
      immunopositivity with CAM 5.2 and AE1/3. All phaeochromocytomas were negative
      with all epithelial markers. CONCLUSIONS: Cauda equina paragangliomas are known
      to stain with cytokeratins; however, occasional paragangliomas from other sites
      may also be immunoreactive with cytokeratins. If the results of
      immunohistochemistry are not interpreted in the clinical and morphological
      context, the failure to recognise that extra-adrenal paragangliomas may on
      occasion react with anticytokeratin antibodies may lead to their being confused
      with metastatic carcinomas.

PMID- 9771452
TI  - Adult hypertrophic pyloric stenosis: case report and review.
AB  - A case of adult hypertrophic pyloric stenosis presented in an older female with
      no apparent predisposing factors which might be likely to precipitate the
      condition. There was a history of chronic dyspepsia and occasional episodes of
      vomiting. No contributory medical history was identified. Barium swallow and
      follow through showed a markedly reduced emptying time of the stomach. A partial
      gastrectomy was eventually done and on histopathological examination a diagnosis
      of adult hypertrophic pyloric stenosis was made.

PMID- 9771453
TI  - The effect of four interventions on the informational content of histopathology
      reports of resected colorectal carcinomas.
AB  - AIM: To investigate the effect of different interventions on the inclusion of
      data items in the histopathology reports of resected colorectal carcinomas. STUDY
      POPULATION: 272 routine histopathology reports on colorectal carcinomas from the
      department of histopathology, Royal Hallamshire Hospital, Sheffield. METHODS: The
      presence or absence of 10 specific data items was recorded for each report. The
      reports were divided into five audit periods. In the initial period reports were
      generated using free text with no agreed guidelines. In period 2, text guidelines
      had been issued; in period 3, flow diagram guidelines had been issued; and in
      periods 4 and 5, template proformas were attached to each specimen request form.
      RESULTS: All interventions produced some increase in inclusion rate for some
      features, but only with the introduction of template proformas did these rates
      approach 100% for all data items. Inclusion rates were 100% for all items in all
      cases reported using a proforma. In the final audit period 96% of specimens were
      reported using proformas. CONCLUSIONS: Template proformas produce a high rate of
      inclusion of data items in reports of colorectal carcinoma resection specimens.

PMID- 9771454
TI  - Stage 0 mucinous adenocarcinoma in situ of the urachus.
AB  - Adenocarcinomas of the urinary bladder are rare (1-5% of bladder tumours) and of
      notoriously poor prognosis. About one third of such tumours arise in urachal
      remnants related to the bladder. This is believed to be the first report of in
      situ change in the urachal remnant. The patient presented with mucusuria and
      computed tomography showed a typical urachal cyst. After excision the cyst was
      found to contain mucinous adenomatous epithelium but without invasion of the
      basal lamina. Pathological stage is the best prognostic indicator in urachal
      tumours. Prompt investigation and management of mucusuria may allow the diagnosis
      of urachal tumours in this preinvasive stage.

PMID- 9771455
TI  - Villous adenoma arising in Meckel's diverticulum.
AB  - The first well documented case of villous adenoma arising in a Meckel's
      diverticulum not associated with a carcinoma is reported. A 21 year old man with
      long history of medically treated ulcerative colitis was admitted to hospital
      with severe pain and bleeding. Total abdominal colectomy and ileo-anal
      anastomosis was performed and during this procedure Meckel's diverticulum
      containing a villous adenoma showing minimal dysplasia was found and resected.
      The diverticulum was lined partly by ileal and partly by gastric epithelium, and
      the villous adenoma originated from the gastric mucosa.

PMID- 9771456
TI  - Ciprofloxacin resistant campylobacter.

PMID- 9771457
TI  - Granulins: the structure and function of an emerging family of growth factors.
AB  - The granulin/epithelin motif defines a family of structurally unique proteins, of
      great evolutionary antiquity, which have been implicated as regulators of cell
      growth. Recurrent in granulin research are the surprising parallels between the
      granulin and EGF systems. Both are cysteinerich peptides of approximately 6 kDa
      that can modify cell growth. They show similar, but not identical, biological
      activities, although granulin/epithelin peptides do not bind EGF receptors; the
      three-dimensional folds of granulin and EGF are partially superimposible; and the
      precursors for mammalian granulin/epithelins and EGF are both organized as
      multiple repeats of conserved cysteine modules. Given the dissimilarity between
      amino acid sequences of members of the granulin/epithelin family and EGF-related
      peptides, the parallelism between the two systems probably represents convergent
      evolution towards related solutions to common biological problems. The
      granulin/epithelin precursor gene is expressed throughout the body, but its
      expression is predominantly in epithelial and haematopoietic cells. There is a
      great deal of versatility in the means by which cells process and handle the
      granulin/epithelin precursor. In some instances, the precursor is secreted intact
      (Zhou et al. 1993), and in others it is stored in a vesicular organelle, such as
      the sperm acrosome (Baba et al. 1993a). It may be processed into small 6-kDa
      peptides, which, in the neutrophil, can also be stored in vesicles (Bateman et
      al. 1990, Couto et al. 1992). The 6-kDa peptide forms, the intact precursor, and
      related proteins such as TGFe, regulate the growth of epithelial and mesenchymal
      cells. Epithelial cells express putative receptors for granulin/epithelin
      peptides and TGFe (Culouscou et al. 1993, Parnell et al. 1995). Thus, although
      much remains to be clarified, granulin/epithelin polypeptides and related
      proteins are emerging as widely distributed potential autocrine and paracrine
      growth modulating factors for epithelial and mesenchymal cells.

PMID- 9771458
TI  - The role of the tissue renin-angiotensin system in the response of the rat
      adrenal to exogenous angiotensin II.
AB  - The tissue renin-angiotensin systems (RAS) may have specific roles that
      complement those of the systemic RAS. In the adrenal, the tissue RAS has been
      implicated in the regulation of glomerulosa tissue growth and function, and in
      mediating the response of the tissue to stimulation by ACTH and potassium ions.
      To examine the role of the rat adrenal tissue RAS in its response to angiotensin
      II stimulation, adrenals were incubated either as bisected glands or as separated
      capsular glands (largely glomerulosa) under control conditions, or in the
      presence of the angiotensin-converting enzyme inhibitor captopril, or of
      angiotensin II, or both. Captopril inhibited the two different tissue
      preparations in different ways. In the capsular gland it inhibited basal
      aldosterone output, but facilitated its response to angiotensin II. In the
      bisected gland, captopril inhibited the response of aldosterone to angiotensin
      II. Other data suggest that one way in which captopril functions is by preventing
      the conversion of fasciculata-generated 18-hydroxydeoxycorticosterone (18-OH-DOC)
      to aldosterone in the glomerulosa. Immunolocalisation of 18-OH-DOC in perfused
      rat adrenal confirms that one function of angiotensin II is to mobilise tissue
      sequestered 18-OH-DOC. The results illustrate the importance of tissue RAS in the
      synthesis of aldosterone and the response to angiotensin II.

PMID- 9771459
TI  - Studies on the role of ACTH in the regulation of adrenal responsiveness and the
      timing of parturition in the ovine fetus.
AB  - A dramatic late-gestation increase in fetal plasma cortisol concentrations is
      critical for the timing of parturition in the sheep. This increase appears to
      depend upon an intact hypothalamo-pituitary unit and is characterised by
      increasing responsiveness of the fetal adrenal gland to ACTH. ACTH has been
      postulated as the critical determinant of the late-gestation cortisol increase;
      however, recent evidence has suggested that other factors, including the ACTH
      precursor, pro-opiomelanocortin, may also be involved. To further define the role
      of ACTH in determining the timing of parturition and the responsiveness of the
      fetal adrenal gland, intact (INT/ACTH) and hypophysectomised (HX/ACTH) fetuses
      received a continuous infusion of ACTH(1-24) from the time of surgery
      (approximately 115 days gestational age (GA)) at a rate we have previously shown
      to generate normal fetal cortisol concentrations and term parturition in HX
      fetuses. A third group of saline-infused intact fetuses (INT/SAL) served as the
      control group. Adrenal responsiveness was assessed by cortisol responses to
      ACTH(1-24) challenges at 120, 130 and 140 days GA. There were no differences
      between the three groups of fetuses in the timing of parturition, the late
      gestation increase in cortisol concentrations or the size of the adrenal cortex.
      In both INT/SAL and INT/ACTH fetuses, there were significant increases in basal
      immunoreactive-ACTH concentrations with advancing GA, although no such increase
      was observed in HX/ACTH fetuses. The proportion of total ACTH immunoreactivity
      present in low molecular weight (LMW) forms in INT/ACTH fetuses was greater than
      that in INT/SAL fetuses, while the level of LMW ACTH in HX/ACTH fetuses was
      intermediate. Both ACTH(1-24)-infused groups of fetuses had dramatically enhanced
      adrenal responsiveness to ACTH(1-24) at all GAs tested when compared with INT/SAL
      fetuses and there was a correlation (in rank order) between the proportion of LMW
      ACTH immunoreactivity and adrenal responsiveness. From these observations it
      appears that there is a separate regulation of adrenal responsiveness from basal
      cortisol concentrations and that an increase in basal cortisol concentrations can
      occur in the absence of an increase in basal ACTH concentrations. Furthermore, an
      increase in adrenal responsiveness does not appear to predict the timing of
      parturition nor basal cortisol concentrations. Taken together with previous
      studies it appears that ACTH plays an essential role in maintaining the growth of
      the fetal adrenal and enhancing its responsiveness, but a late-gestation increase
      in ACTH concentrations is not required to regulate basal cortisol concentrations
      or the timing of parturition.

PMID- 9771460
TI  - Regulation of oxytocin receptor in the placentome capsule throughout pregnancy in
      the ewe: the possible role of oestradiol receptor, progesterone receptor and
      aromatase.
AB  - The hormonal regulation of uterine oxytocin receptors (OTR) during the
      establishment of pregnancy and at parturition has been studied extensively, but
      little information is available during mid-pregnancy. This study investigated the
      localisation of OTR mRNA in the ovine placentome throughout gestation and related
      this to expression patterns for the putative regulatory agents aromatase,
      oestradiol receptor, progesterone receptor and oxytocin. Placentomes were
      collected at regular intervals throughout pregnancy for in situ hybridisation
      analysis and immunocytochemistry (oestradiol receptor only). Results were
      quantified by optical density measurements of autoradiographs. Progesterone
      receptor mRNA was localised to the caruncular tissues on day 30 but became
      undetectable by day 34. Aromatase mRNA appeared in the fetal villi at days 34-40,
      with concentrations peaking at days 52-55 and again at days 132-137. Oestradiol
      receptor mRNA was localised to the caruncular tissues from days 13 to 30 and
      found in the maternal villi and placentome capsule from days 45 to 70. Oestradiol
      receptor protein was barely detectable in either tissue. OTR mRNA was localised
      to the placentome capsule at days 34-40, remaining high at day 45 and declining
      to basal levels by days 132-137. Oxytocin mRNA was not detected in the
      placentome. IN CONCLUSION: (1) progesterone acting via its receptor may suppress
      the expression of aromatase and OTR in early pregnancy; (2) the up-regulation of
      OTR expression in the capsule may not involve the oestradiol receptor; (3) there
      is a differential regulation between different regions of the uterus as the
      increase in the placentome capsule occurs at a time when concentrations in the
      rest of the endometrium and myometrium remain low; (4) oestradiol receptor
      expression in the placentome may be regulated at the translational level; and (5)
      there is no local production of oxytocin in the sheep placenta. The role of ORTs
      in the capsule during mid-pregnancy remains to be determined.

PMID- 9771461
TI  - The co-localization of stanniocalcin protein, mRNA and kidney cell markers in the
      rat kidney.
AB  - Stanniocalcin (STC) is a glycoprotein hormone that was first discovered in fish
      and recently identified in mammals. STC immunoreactive (STCir) cells have been
      identified in rat kidney and there is also evidence that the hormone functions as
      a regulator of renal phosphate homeostasis. In the present study we have
      identified STCir cells and tubules in the rat kidney by correlative
      immunocytochemistry using antibodies to STC and specific antigenic markers (Tamm
      Horsfall protein and anion exchanger-1). The cellular sites of STC gene
      expression were also identified by in situ hybridization. Correlative
      immunocytochemistry revealed that STCir was present in all proximal straight
      tubule cells, all cortical thick ascending limb cells, all distal convoluted
      tubule cells, and both principal and alpha-intercalated cells of the collecting
      duct system. On the other hand, in situ hybridization revealed that the STC gene
      was expressed only in cortical and medullary collecting duct cells. This suggests
      either that STC is being sequestered by segments that do not express the gene
      (making them putative targets of the hormone), or that STC mRNA levels were
      simply too low in these other segments to be detected by in situ hybridization.

PMID- 9771462
TI  - Glucose utilization rate and pancreatic hormone response to oral glucose loads
      are influenced by the migratory condition and fasting in the garden warbler
      (Sylvia borin).
AB  - Substrate utilization and regulatory mechanisms of metabolism were studied in
      migratory garden warblers by measuring plasma levels of glucose, free fatty acids
      (FFAs), beta-hydroxybutyrate, insulin and glucagon in response to oral glucose
      loads. Three different physiological states were examined: (a) the autumnal
      migratory period on a high and (b) on a fasted low body mass level, and (c) the
      postmigratory period with low body mass. Glucose tolerance was better in the
      postmigratory lean than fat condition. However, total food deprivation of 5-7
      days with fat birds reaching their lean body mass further reduced the glucose
      utilization rate. Initial levels of FFAs were highest in the starved,
      intermediate in the fat and lowest in the lean condition. Changes in plasma FFAs
      during glucose tolerance tests were opposite to those of the glucose levels. Ten
      minutes after the glucose load plasma glucagon levels decreased and insulin
      increased. These effects were larger in the fat than in the postmigratory lean
      condition. There were no differences between sexes. It appears that during
      premigratory and migratory periods glucose utilization may be inhibited by a more
      favorable oxidation of fatty acids as would be predicted by the glucose fatty
      acid cycle. However, the inhibition of glucose utilization seems to be
      counterregulated by stronger responses of insulin and glucagon. These results may
      be important also in the consideration of food selection during premigratory
      periods and refueling abilities of birds crossing ecological barriers.

PMID- 9771463
TI  - Effect of nitric oxide on rat adrenal zona fasciculata steroidogenesis.
AB  - The present study was designed to investigate the role of nitric oxide (NO) in
      the regulation of adrenocortical function. Different NO donors, such as sodium
      nitroprusside (SNP), S-nitroso-L-acetyl penicillamine, diethylamine/NO complex
      sodium salt and diethylenetriamine NO adduct, significantly decreased
      corticosterone production both in unstimulated and in corticotropin-stimulated
      zone fasciculata adrenal cells, in a dose-dependent manner. The effect of SNP was
      reversed by ferrous hemoglobin. A selective inhibitor of NO synthase, L-NG-nitro
      arginine significantly increased corticosterone secretion. The effect of SNP was
      not mediated by cGMP as permeable cGMP analogs did not reproduce its inhibitory
      effect. SNP significantly inhibited the steroidogenesis stimulated by 8Br-cAMP
      and 22(R)-OH-cholesterol, but was ineffective when corticosterone was produced in
      the presence of exogenously added pregnenolone. Moreover, the conversion of
      [3H]cholesterol to [3H]pregnenolone and the production of pregnenolone or
      progesterone (assessed by RIA) were significantly decreased by SNP. Taken
      together, these results suggest that NO may be a negative modulator of adrenal
      zona fasciculata steroidogenesis.

PMID- 9771464
TI  - Long-term in vitro exposure to high glucose increases proinsulin-like-molecules
      release by isolated human islets.
AB  - The aim of this study was to determine the effect of long-term in vitro exposure
      to high glucose on the release and content of proinsulin and insulin in human
      islets. After 48 h culture in CMRL medium at 5.5 mM (control islets) and 16.7 mM
      glucose (experimental islets), islets were perifused and acutely stimulated with
      16.7 mM glucose, followed by 3.3 mM glucose. Compared with control islets,
      experimental islets showed a higher basal release of true insulin and proinsulin
      like-molecules (PLM), with no increase of true insulin and PLM release in
      response to 16.7 mM glucose, and a paradoxical true insulin release in response
      to 3.3 mM glucose; the PLM/total insulin ratio increased significantly after 16.7
      mM glucose. Moreover these islets showed a decreased true insulin content and an
      increased PLM/total insulin ratio. Quantitative ultrastructural analysis of
      granules, supported by double gold immunostaining with monoclonal antibodies
      against proinsulin and insulin, showed an increased proinsulin to insulin ratio
      in beta-cells from experimental islets. These data support in vitro what was
      recently shown in vivo, and further confirm that culture in high glucose is a
      useful tool to mimic the effect of in vivo chronic hyperglycemia on human beta
      cell function.

PMID- 9771465
TI  - Effects of unilateral or bilateral superior ovarian nerve section in prepubertal
      rats on the ovulatory response to gonadotrophin administration.
AB  - The modulating effects of ovarian innervation reaching the ovary through the
      suspensory ovarian nerve on the reactivity of the ovaries to gonadotrophins were
      analysed. Juvenile rats (32 days old), with or without unilateral or bilateral
      section of the superior ovarian nerve, were injected with 8 iu of pregnant mare
      serum gonadotrophin (PMSG), 10 iu of human chorionic gonadotrophin (hCG) or with
      8 iu of PMSG followed 56 h later with 10 iu of hCG. Treatments were given
      immediately after surgery or 4 days later, and the rats were killed on the day of
      first vaginal oestrus. In rats with unilateral section, treatment with PMSG did
      not induce full ovulatory response by the denervated ovary whether the treatment
      was applied immediately or 4 days after surgery (0/11 rats treated immediately
      ovulated vs 5/5 (sham) and 11/12 (control, P < 0.05 Fisher's exact probability
      test), and 4/19 did when treatment was done 4 days after surgery vs 8/10 (sham)
      and 11/12 (control, P < 0.05). The rats with bilateral section receiving the same
      hormonal treatment, PMSG administration, ovulated. The number of ova shed by the
      left ovary was similar to those of the control, while the right ovary released
      fewer ova. Stimulation with hCG immediately after unilateral section did not
      induce ovulation in normal or denervated ovary. When the treatment was applied 4
      days after surgery, ovulation was observed only in the innervated ovary. In the
      rats with bilateral section, hCG injection induced ovulation in both ovaries. In
      those rats with unilateral section of the superior ovarian nerve, the treatment
      with PMSG + hCG given immediately after surgery resulted in a compensatory
      ovulation by the innervated ovary (the number of ova shed/ovulating animal was
      significantly higher than those released by control or sham-operated animals:
      left section, number of ova shed by the right ovary 7.6 +/- 0.3 vs 5.5 +/- 0.8
      and 4.9 +/- 1 respectively, P < 0.05; right section, number of ova shed by the
      left ovary 10.2 +/- 0.6 vs 4.4 +/- 1.1 and 7.0 +/- 0.9, P < 0.05), while the
      denervated one showed a lower ovulation rate as well as a smaller number of ova
      shed than those by the control animals. When the hormonal replacement was given 4
      days after surgery, such compensatory ovulation was observed in the left ovary of
      those rats with a section of the right nerve (14.3 +/- 2.6 vs 4.4 +/- 1.1 and 6.5
      +/- 1.1, P < 0.05). When the PMSG + hCG treatment was applied to animals with
      bilateral section of the superior ovarian nerve, the ovulation rate by the right
      ovary was significantly lower than in control and sham-operated treated animals
      (2/10 vs 11/11 and 6/7, P < 0.05). Because the ovaries receive innervation
      through the superior ovarian nerve, the ovarian plexus and the vagus nerve, the
      results obtained in unilateral denervated animals suggest that the innervation of
      the ovary via the superior ovarian nerve regulates in a stimulatory way the
      effects of gonadotrophin resulting in ovulation. The ovulation induced by
      hormonal treatment of rats with bilateral section of the superior ovarian nerve
      suggests that the effects of bilateral section on ovulation are not the addition
      of the effects of left and right denervation, implying the existence of a
      modulatory effect in gonadotrophin action on ovulation via other neural pathways.

PMID- 9771466
TI  - Differential distribution of gelatinases and tissue inhibitor of
      metalloproteinase-1 in the rat ovary.
AB  - The distribution of gelatinases/matrix metalloproteinases-2 and -9 (MMP-2 and MMP
      9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in neonatal and
      gonadotropin-primed immature rat ovaries was studied by immunofluorescent
      microscopy. Immature female Long-Evans rats were primed with 15 IU pregnant
      mare's serum gonadotropin (PMSG) in 100 microliters PBS. Two days later, to
      induce ovulation, the rats were injected with human chorionic gonadotropin (hCG,
      5 IU/100 microliters PBS). The animals were killed at appropriate times and the
      ovaries removed and processed for cryostat or paraffin sectioning. Ovaries were
      also obtained from 7-day-old neonatal rats and processed as above. In the
      neonatal rat ovary, MMP-2 was present in the follicle and in the ovarian surface
      epithelium. MMP-9 was not detectable in the neonatal ovary. TIMP-1 was present in
      the oocyte and in the surface epithelium. In the PMSG-primed ovary, MMP-2 was
      present in the granulosa and thecal cells of the ovary. MMP-9 distribution,
      however, was restricted to the interstitial and thecal cells. TIMP-1 was mainly
      present in the blood vessels and thecal cells, with minor staining in the
      granulosa cells. In the developing corpus luteum, luteal and endothelial cells
      were positive for MMP-2. MMP-9 localization was restricted to the plasma membrane
      of the luteal and interstitial cells. TIMP-1 was clearly observed in the luteal
      capillaries and, to a lesser extent, in the luteal cell plasma membrane. This
      distribution of MMP-2, MMP-9, and TIMP-1 in the corpus luteum persisted
      throughout the life span of the corpus luteum. The spatial and temporal
      distribution of the gelatinases and TIMP-1 suggests unique roles for these
      proteins in the rat ovary.

PMID- 9771467
TI  - The role of gonadectomy and testosterone replacement on thymic luteinizing
      hormone-releasing hormone production.
AB  - We and others have identified luteinizing hormone-releasing hormone (LHRH) in
      cells of the immune system in both animals and humans. LHRH is an
      immunostimulant, and testosterone is an immunosuppressant. Because testosterone
      is known to modulate the concentrations of hypothalamic LHRH, we wondered whether
      testosterone might also alter the concentrations of rat thymic LHRH. Two weeks
      after castration or sham castration, adult male rats were implanted with either
      vehicle or testosterone capsules. All animals were killed 4 days after capsule
      implantation. Thymic LHRH concentration increased significantly in castrated
      animals. Testosterone replacement prevented this increase. The concentration of
      the LHRH precursor, proLHRH, decreased significantly, but testosterone
      replacement prevented this decrease. Steady-state concentrations of LHRH mRNA
      were not changed by castration or by hormonal replacement. In contrast to the
      post-castration increase in thymic LHRH, LHRH content of the hypothalamus
      decreased significantly. Whereas concentrations of LHRH were lower in the thymus
      than in the hypothalamus, proLHRH concentrations were much greater in the thymus.
      These data suggest that gonadal manipulation modulates LHRH molecular processing
      and its tissue concentration in the thymus in addition to those in the
      hypothalamus, and that the regulation of LHRH molecular processing by
      testosterone in the hypothalamus is different from that in the thymus.

PMID- 9771468
TI  - Tissue-specific induction of 17 beta-hydroxysteroid dehydrogenase type IV by
      peroxisome proliferator chemicals is dependent on the peroxisome proliferator
      activated receptor alpha.
AB  - The 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) family of proteins
      regulates the levels of the active 17 beta-hydroxy forms of sex steroids. The
      expression of 17 beta-HSD type IV is induced by peroxisome proliferator chemicals
      (PPC) in rat liver. In order to characterize more generally the impact of PPC on
      17 beta-HSD expression, we determined (1) if expression of other members of the
      17 beta-HSD family was coordinately induced by PPC exposure, (2) the tissues in
      which 17 beta-HSD was induced by PPC, and (3) whether the induction of 17 beta
      HSD by PPC was dependent on the peroxisome proliferator-activated receptor alpha
      (PPAR alpha), the central mediator of PPC effects in the mouse liver. The mRNA
      levels of 17 beta-HSD I, II, and III were not altered in the liver, kidney, and
      testis or uterus of rats treated with PPC. The mRNA or 80 kDa a full-length
      protein levels of 17 beta-HSD IV were strongly induced in liver and kidney, but
      not induced in adrenals, brown fat, heart, testis, and uterus of rats treated
      with diverse PPC. In liver and kidneys from treated rats, additional proteins of
      66 kDa, 56 kDa, and 32 kDa were also induced which reacted with the anti-17 beta
      HSD IV antibodies and were most likely proteolytic fragments of 17 bega-HSD IV.
      Treatment of mice which lack a functional form of PPAR alpha with PPC,
      demonstrated that PPC-inducibility of 17 beta-HSD IV mRNA or the 80 kDa protein
      was dependent on PPAR alpha expression in liver and kidney. Our results
      demonstrate that 17 beta-HSD IV is induced by PPC through a PPAR alpha-dependent
      mechanism and support the hypothesis that exposure to PPC leads to alterations in
      sex steroid metabolism.

PMID- 9771469
TI  - Premature elevation in serum insulin-like growth factor-I advances first
      ovulation in rhesus monkeys.
AB  - Previous data suggest that developmental increases in peripheral concentrations
      of insulin-like growth factor-I (IGF-I) may be one of several neuroendocrine
      signals that regulate the timing of puberty. In order to test this hypothesis
      further, normal juvenile female rhesus monkeys (Con; n = 6) were compared with
      age-matched animals (Igf; n = 4) which received a constant subcutaneous infusion
      of recombinant human IGF-I (110 micrograms/kg/day) from 18 through 36 months of
      age. Menstrual bleeding was monitored and ovulation was inferred from a sustained
      rise in serum progesterone. In order to assess the sensitivity of luteinizing
      hormone-releasing hormone (LHRH) neurons to excitation, the response of serum LH
      to the acute administration of the glutamate receptor agonist N-methyl-D, L
      aspartic acid (NMDA) was assessed prior to menarche, 2 months following menarche,
      and during the follicular phase of a female's third ovulation or 50 days after a
      female's first ovulation. In addition, the pituitary response of LH secretion to
      an LHRH agonist was assessed during the follicular phase of a female's fourth
      ovulation or 75 days following her first ovulation. IGF-I treatment effectively
      elevated serum concentrations by more than 86% of the values observed in Con
      animals. Although the treatment also enhanced the developmental increase in IGF
      binding protein-3 (IGFBP-3), IGF-I was increased proportionately more, resulting
      in a significantly higher molar ratio of IGF-I:IGFBP-3 in treated females
      throughout the course of the study. Treatment with IGF-I did not affect age at
      menarche but did significantly advance the age of first ovulation. Consequently,
      the interval between menarche and first ovulation was significantly shorter in
      Igf compared with Con females. Although the total number of ovulations exhibited
      by Igf (3.8 +/- 0.3) and Con females (3.0 +/- 0.5) in the 12 months following
      menarche was similar, significantly more of these were characterized by normal
      luteal phase progesterone secretion in Igf (100% +/- 0) compared with Con females
      (64% +/- 17). An analysis of cycles with a normal luteal phase revealed that
      serum estradiol during the luteal phase was significantly higher in Igf compared
      with Con females. Finally, IGF-treated females responded to NMDA treatment with a
      significantly greater increase in serum LH following menarche but not prior to
      menarche. In contrast, the response of serum LH to an LHRH agonist did not differ
      between Igf and Con females. These data suggest that the premature elevation in
      IGF-I levels, and consequently the ratio of IGF-I:IGFBP-3, accelerates the tempo
      of the final stages of puberty in rhesus monkeys. This action of IGF-I is
      probably the result of an increase in LHRH neuronal activity and is not due to a
      change in pituitary sensitivity to LHRH stimulation. In addition, ovarian
      sensitivity to LH stimulation during the luteal phase is also increased by IGF-I.
      Taken together, these data suggest that developmental increases in peripheral IGF
      I secretion participate in the neuroendocrine regulation of puberty in female
      primates.

PMID- 9771470
TI  - Oogenesis in Atlantic salmon (Salmo salar L.) occurs by zonagenesis preceding
      vitellogenesis in vivo and in vitro.
AB  - Fish oogenesis represents pleiotropic cytodifferentiative programs including
      hepatic synthesis of the molecular components for both the eggshell and the
      oocytic energy deposits. Both hepatic processes are directly controlled by plasma
      levels of estradiol (E2), and injected E2 induces both biogenetic processes in
      prepubertal fish of both sexes. This work compares the temporal pattern of E2
      induced biosynthesis of zona radiata proteins (zr-proteins) and vitellogenin in
      Atlantic salmon (Salmo salar L.) in vivo and in vitro. We monitored the presence
      of plasma zr-proteins and vitellogenin, using homologous polyclonal antiserum to
      zr-proteins and a monoclonal antibody to vitellogenin. Zr-proteins were induced
      by all E2 concentrations (0.001-1.1 mg/kg body weight (bw)) within one week of
      exposure while vitellogenin was not induced until two weeks post-injection and
      then only in plasma from fish injected with high E2 concentrations (0.4 mg or 1.1
      mg/kg bw). After E2 treatment, hepatocytes isolated from male fish synthesized zr
      proteins and vitellogenin in vitro. However, zr-proteins were secreted into the
      medium two days before vitellogenin, as measured by ELISA. The data indicate a
      preferential induction of zr-proteins compared with vitellogenin, both with
      regard to E2 sensitivity and response time to E2 treatment. These findings
      suggest an obligate sequence in salmon oogenesis. During sexual maturation low E2
      levels at first induce only zonagenesis, while increasing levels of E2
      subsequently induce both zonagenesis and vitellogenesis. In nature, the interval
      between zonagenesis and vitellogenesis may, therefore, be considerable. The data
      suggest new control mechanisms in fish oogenesis.

PMID- 9771471
TI  - Regulation of Leydig cells through a steroidogenic acute regulatory protein
      independent pathway by a lipophilic factor from macrophages.
AB  - The purpose of this investigation was to study the mechanism of action of a
      macrophage-derived factor that stimulates steroid production by Leydig cells.
      This factor increased testosterone production within 30 min, and reached a half
      maximal response by 6-8 h. At a maximal dose, it stimulated testosterone
      production 20-fold at 24 h. Its efficacy was consistently higher than that
      achieved with a maximal dose of human chorionic gonadotropin (hCG). However,
      Leydig cells treated with a maximal dose of both the macrophage-derived factor
      and hCG secreted the same amount of testosterone as when given a maximal dose of
      only the macrophage-derived factor. The macrophage-derived factor did not require
      new protein synthesis to stimulate testosterone production, nor did it alter the
      amount of steroidogenic acute regulatory protein (StAR). While the macrophage
      derived factor required an active cholesterol side-chain cleavage complex system,
      it did not alter the capacity of this enzyme complex. Finally, the macrophage
      derived factor was unable to stimulate the production of progesterone by isolated
      mitochondria. In summary, the macrophage-derived factor is a highly active, acute
      regulator of steroidogenesis that acts through a high capacity StAR-independent
      pathway.

PMID- 9771472
TI  - The effect of season and melatonin on GnRH-induced LH secretion in oestradiol
      treated orchidectomized sheep.
AB  - The biphasic effect of oestradiol (E2) on gonadotrope responsiveness is clearly
      evident in orchidectomized sheep (wethers) receiving E2 and hourly pulses of
      GnRH. We hypothesized that the duration of E2-induced reduction in gonadotrope
      responsiveness differed between the breeding (November) and anoestrous (May)
      seasons in sheep. To test this hypothesis wethers (n = 6/group) were infused
      (i.v.) with E2 (2 micrograms/50 kg per h) and received hourly pulses of GnRH (200
      ng/50 kg per pulse) or saline in May or November. The pattern of LH secretion
      during the 72 h infusion period was determined. Serum concentrations of LH did
      not differ with season in control wethers receiving vehicle alone. Similarly,
      continuous infusion of E2 resulted in a 3-fold reduction in serum LH,
      irrespective of season. This E2-induced suppression of serum LH was reversed by
      concurrent episodic delivery of GnRH. The interval between initiation of infusion
      and return of pretreatment concentrations of LH was taken as a measure of the
      duration of E2-induced suppression of gonadotrope responsiveness. The duration of
      this E2-dependent response varied with season, with suppression of gonadotrope
      responsiveness more prolonged (P < 0.05) in May (36.7 +/- 2.9 h) than in November
      (14.3 +/- 1.1 h). In a companion study we examined the effect of melatonin on the
      duration of E2-induced suppression of gonadotrope responsiveness. Wethers
      received blank or melatonin-containing implants in March. Sixty days after
      implant insertion (mid-May) wethers received E2 (2 micrograms/50 kg per h) and
      hourly pulses of GnRH (200 ng/50 kg per pulse) or saline for 72 h. Continuous
      delivery of E2 alone resulted in a 3-fold decrease in serum concentrations of LH
      in both control and melatonin-treated wethers. The duration of E2-induced
      suppression of gonadotrope responsiveness in animals receiving E2 and GnRH was
      extended (P < 0.05) in wethers with blank implants (48.0 +/- 0.7 h), relative to
      the duration of suppression in melatonin-treated wethers (14.5 +/- 1.0 h). Taken
      together these data indicate that E2-induced suppression of gonadotrope
      responsiveness is more extended during the anoestrous season. However, this
      seasonal effect can be reversed by continuous administration of melatonin.

PMID- 9771473
TI  - The role of endogenous opioids in neurohypophysial and hypothalamo-pituitary
      adrenal axis hormone secretory responses to stress in pregnant rats.
AB  - Endogenous opioid regulation of neurohypophysial and hypothalamo-pituitary
      adrenal (HPA) axis hormone secretion in response to forced swimming (90 s in deep
      water at 19 degrees C) was investigated in virgin and 21-day-pregnant rats. There
      was no difference in basal plasma oxytocin concentrations between pregnant and
      virgin rats, but the opioid antagonist, naloxone, increased basal oxytocin
      secretion in the pregnant rats. Forced swimming increased oxytocin secretion
      similarly in pregnant and virgin rats, and this response was enhanced by
      naloxone. In pregnant rats naloxone had a greater effect (by 3.1-fold) than in
      virgins, showing stronger endogenous opioid restraint of an enhanced oxytocin
      secretory response to stress in pregnancy. Vasopressin secretion was not
      increased with forced swimming in virgin or pregnant rats, and naloxone had no
      effect. ACTH and corticosterone secretion in response to forced swimming was
      attenuated in pregnant rats compared to virgin rats, measured at 5 min. Naloxone
      had no effect on basal plasma ACTH or corticosterone concentration, but it
      reduced ACTH secretion in virgin rats 5 min after forced swimming; in pregnant
      rats naloxone had no such effect. Naloxone removed the pregnancy-related
      attenuation in corticosterone secretion measured at 5 min after forced swimming.
      Fifteen minutes after forced swimming, plasma corticosterone concentrations were
      not different between groups. In the late-pregnant rats, the increases in plasma
      ACTH and corticosterone induced by forced swimming were significantly prolonged
      compared to virgins. The results show that endogenous opioid inhibition emerges
      in pregnancy to restrict the responses of oxytocin neurones to a stressor. In
      contrast, the endogenous opioid enhancement of mechanisms regulating HPA axis
      secretory responses in virgin rats is not evident during pregnancy.

PMID- 9771474
TI  - Germinal centre cell kinetics.
AB  - The germinal centre is a fundamental component of the humoral immune response,
      representing a unique microenvironment where antigen-activated B lymphocytes
      undergo clonal expansion, mutate their immunoglobulin, and are subject to a
      stringent selection process based on their antigen affinity. This review
      highlights recent advances in the understanding of the cell kinetic process of
      activation, proliferation, differentiation, and death of germinal centre cells,
      which are beginning to provide important insights into the regulation of this
      highly complex reaction. Their definition may have considerable pathological
      import given the involvement of the germinal centre in non-Hodgkin's lymphomas
      and recent evidence suggesting that abnormal germinal centre reactions may be
      involved in the pathogenesis of Hodgkin's disease and some autoimmune diseases.

PMID- 9771475
TI  - The erbB/HER type 1 tyrosine kinase receptor family.
AB  - The erb type 1 tyrosine kinase receptors are important for mediating
      proliferation and differentiation, and aberrant activation may contribute to
      tumour development and progression. They comprise epidermal growth factor
      receptor (EGFR), c-erbB-2, c-erbB-3, and c-erbB-4. There are overlaps and
      differences in the cellular distribution of the four receptors, which is of
      significance since they can form heterodimers that give differing responses to
      different ligands. The different distributions could be of particular importance
      in cancer if therapeutic modalities are identified to inhibit or stimulate the
      different ligands.

PMID- 9771476
TI  - Expression of the c-erbB-4/HER4 protein and mRNA in normal human fetal and adult
      tissues and in a survey of nine solid tumour types.
AB  - The c-erbB-4/HER4 receptor belongs to the family of the type I growth factor
      receptors. Mouse monoclonal antibodies have been raised to the cytoplasmic domain
      of the c-erbB-4 receptor and characterized; the antibody HFR-1 has been used to
      determine the pattern of expression of the c-erbB-4 protein immunohistochemically
      in formalin-fixed, paraffin-embedded adult and fetal tissues. The expression of c
      erbB-4 mRNA was determined by using 35S-labelled riboprobes and tissue in situ
      hybridization. c-erbB-4 is widely expressed in many adult and fetal tissues,
      including the lining epithelia of the gastrointestinal, urinary, reproductive,
      and respiratory tracts, as well as the skin, skeletal muscle, circulatory,
      endocrine, and nervous systems. The developing brain and heart notably express
      high levels of this receptor. The pattern of c-erbB-4 protein expression is also
      reported in a survey of common solid human cancers. Loss of expression was noted
      in 40-80 per cent of adenocarcinomas and up to 100 per cent of squamous cell
      carcinomas, whereas overexpression was observed in about 10-20 per cent of
      adenocarcinomas and astrocytomas. In general, the pattern of c-erbB-4 expression
      in normal tissues and cancers suggests that it tends to be associated with the
      differentiated compartment.

PMID- 9771477
TI  - APC in the regulation of intestinal crypt fission.
AB  - The functional effects of APC (adenomatous polyposis coli gene) germ-line
      mutations on crypt fission and cell proliferation were investigated in the normal
      intestine of human familial adenomatous polyposis (FAP) and multiple intestinal
      neoplasia (MIN) mice. Compared with controls, there was a 19-fold increase in the
      proportion of crypts in fission in FAP colon [95 per cent confidence interval
      (CI): 11-32, P < 0.0001], and a 75 and 61 per cent increase in MIN colon (95 per
      cent CI: 1.08-2.82, P < 0.02) and small bowel, respectively (95 per cent CI: 1.31
      1.99, P < 0.001). In marked contrast, no significant differences in intra-cryptal
      epithelial cell proliferation or mitotic distribution were seen. Furthermore,
      10.9 per cent of crypts in FAP were in asymmetrical fission as opposed to only 1
      per cent in controls (P = 0.001). The largest relative increases in MIN crypt
      fission were in the colon (proximal and distal colon:190 per cent, P = 0.02 and
      83 per cent, P = 0.01), suggesting that Apc mutations exert their maximal
      influence site-specifically. However, sites with the highest relative increases
      were also those with the largest eventual tumour sizes, but not the highest polyp
      counts. Three-dimensional serial section reconstruction analysis corroborated
      that FAP adenomas enlarge by crypt fission, which was frequently both
      asymmetrical and atypical. It is proposed that the absence of an increase in
      intestinal cell division infers that APC regulates intestinal crypt
      differentiation, specifically through the crypt cycle. This role appears
      analogous to the control of axis re-duplication in embryonic development, when
      downstream targets of APC are over-expressed. It is concluded that in vivo, the
      major defect in pre-neoplastic intestine harbouring APC mutations is elevated
      rates of crypt fission, and that this is also the mode by which micro-adenomas
      enlarge.

PMID- 9771478
TI  - Matrix metalloproteinase-1 is associated with poor prognosis in oesophageal
      cancer.
AB  - The matrix metalloproteinases (MMPs) are a family of closely related proteolytic
      enzymes which are involved in the degradation of different components of the
      extracellular matrix. There is increasing evidence to indicate that individual
      MMPs have an important role in tumour invasion and tumour spread. Monoclonal
      antibodies specific for MMP-1, MMP-2, or MMP-9 have been produced, using as
      immunogens peptides selected from the amino acid sequences of individual MMPs.
      The presence of MMP-1, MMP-2, and MMP-9 in oesophageal cancer was investigated by
      immunohistochemistry on formalin-fixed, wax-embedded sections of oesophageal
      cancers. The relationship of individual MMPs to prognosis and survival was
      determined. MMP-1 was present in 24 per cent of oesophageal cancers, while MMP-2
      and MMP-9 were present in 78 and 70 per cent of tumours, respectively. The
      presence of MMP-1 was associated with a particularly poor prognosis (log rank
      test 8.46, P < 0.004) and was an independent prognostic factor (P = 0.02). The
      identification of individual MMPs in oesophageal cancer provides a rational basis
      for use in the treatment of oesophageal cancer of MMP inhibitors which are
      currently undergoing clinical trial.

PMID- 9771479
TI  - E-cadherin and alpha-, beta-, and gamma-catenin protein expression in relation to
      metastasis in human breast carcinoma.
AB  - In the metastatic process, various cell-cell adhesion molecules seem to play an
      important role. E-cadherin, a transmembrane protein with an extracellular and an
      intracellular domain, is one of the key players involved in cell-cell adhesion.
      The function of E-cadherin in preventing metastasis in tumour development is
      believed to be dependent on intracellular catenins. In a previous study, the
      expression of E-cadherin was examined in a series of human breast carcinomas. In
      that study, down-regulation of E-cadherin failed to correlate with lymph node
      and/or distant metastasis. In the present study, the expression of alpha-, beta-,
      and gamma-catenins has been examined in a subset of the same tumours in order to
      evaluate their possible role in breast cancer metastasis. Tumour tissues from 90
      primary breast carcinomas were immunostained for alpha-, beta-, and gamma
      catenins. Reduced or absent immunoreactivity in the tumour tissue was seen in 63
      (70.0 per cent) for alpha-catenin, in 50 (55.6 per cent) for beta-catenin, and in
      50 (55.6 per cent) for gamma-catenin. Reduced expression of each of the catenins
      alone failed to correlate to metastasis. However, when all of the four proteins
      (E-cadherin, alpha-catenin, beta-catenin, and gamma-catenin) were analysed as one
      group, a significant association was seen between reduction in immunoreactivity
      of at least one of these four proteins and the presence of metastases. These
      results indicate that if one of these proteins is down-regulated, the function of
      the others in suppressing metastasis is altered. A significant association was
      seen between lobular invasive tumours and beta-catenin expression.

PMID- 9771480
TI  - Beta- and gamma-catenin expression in thyroid carcinomas.
AB  - Cadherins are calcium-dependent cell-cell adhesion molecules whose intracellular
      domain forms a complex with proteins required for their function, called
      catenins. Down-regulation of cadherins has frequently been detected in many types
      of human carcinomas, being associated with tumour progression. The present study
      investigates the immunohistochemical expression of E-cadherin and beta- and gamma
      catenin in 27 human thyroid carcinomas. E-cadherin immunoreactivity was found to
      be decreased at cell-cell contacts in 8/15 (53 per cent) papillary, 5/7 (71 per
      cent) follicular, and 5/5 (100 per cent) anaplastic carcinomas. Beta-catenin
      membrane localization was found to be decreased in 6/15 (40 per cent) papillary,
      2/7 (28 per cent) follicular, and 5/5 (100 per cent) anaplastic carcinomas. Gamma
      catenin expression was partially or totally lost in 13/15 (86 per cent)
      papillary, 6/7 (85 per cent) follicular, and 5/5 (100 per cent) anaplastic
      carcinomas. A normal pattern of expression for these three molecules was observed
      in areas of normal tissue in each sample. These data indicate that in addition to
      E-cadherin, catenins are also down-regulated at cell-cell junctions in thyroid
      tumours and could represent potentially useful differentiation and/or
      transformation markers. The high frequency of alterations of gamma-catenin
      expression found in thyroid carcinomas suggests an important role for this gene
      product in thyroid carcinogenesis.

PMID- 9771481
TI  - Longitudinal evaluation of cytogenetic aberrations in prostatic cancer: tumours
      that recur in time display an intermediate genetic status between non-persistent
      and metastatic tumours.
AB  - Only limited data are available on chromosomes specifically involved in prostatic
      tumour progression. This study has evaluated the cytogenetic status of primary
      prostatic carcinomas, local tumour recurrences, and distant metastases,
      representing different time points in prostatic tumour progression. Interphase in
      situ hybridization (ISH) was applied with a set of (peri) centromeric DNA probes,
      specific for chromosomes 1, 7, 8 and Y, to routinely processed tissue sections of
      73 tumour specimens from 32 patients. Longitudinal evaluation was possible in 11
      cases with local recurrence and nine cases with distant metastases. The remaining
      12 patients showed no evidence of local recurrence or distant metastasis after
      radical prostatectomy on follow-up (mean 60.5 months) and served as a reference.
      Numerical aberrations of at least one chromosome were found in 27 per cent of the
      local recurrences and 56 per cent of the distant metastases. In decreasing order
      of frequency, +8, +7, and -Y were observed in the recurrences and +8, +7, -Y, and
      +1 in the distant metastases. Evaluation of the corresponding primary tumour
      tissue of the recurrence group showed numerical aberrations in 45 per cent of
      cases. The aberrations found were, in decreasing order of frequency, -Y, +7, and
      +8. In the concomitant primary tumour tissue of the distant metastasis group,
      numerical aberrations were detected in 67 per cent of cases. The aberrations most
      frequently encountered were +8, -Y, followed by +7. In four cases, a concordance
      was found between the primary tumour and its recurrence or distant metastasis.
      Discrepancies might have been caused by cytogenetic heterogeneity. Comparison of
      the primary tumour tissue of the reference, the recurrence, and the distant
      metastasis groups showed a significant increase for the percentage of cases with
      numerical aberrations (Ptrend = 0.02). Likewise, a trend was seen for gain of
      chromosome 7 and/or 8 (Ptrend < 0.05). The number of DNA aneuploid tumours also
      increased in these different groups (Ptrend = 0.03). These data suggest that
      cancers which recur in time display an intermediate position between tumours of
      disease-free patients and metastatic cancers.

PMID- 9771482
TI  - Expression of transforming growth factor beta isoforms in osteosarcoma variants:
      association of TGF beta 1 with high-grade osteosarcomas.
AB  - Studies on osteosarcoma cell lines point to the potential importance of
      transforming growth factor beta (TGF beta) as an autocrine factor which controls
      the growth of human osteosarcomas. To define further the role of TGF beta
      isoforms in these neoplasms, a series of 27 osteosarcomas was studied using
      immunohistochemical, mRNA in situ hybridization, and reverse transcriptase
      polymerase chain reaction (RT-PCR) techniques. All 14 central high-grade
      osteosarcomas, two telangiectatic osteosarcomas, and one high-grade surface
      osteosarcoma showed cytoplasmic immunoreactivity for TGF beta 1, -2, and -3. The
      expression of TGF beta 1 was moderate or diffuse in 14 cases (82.3 per cent),
      while low expression was detected in only three cases (17.7 per cent). For TGF
      beta 2 and -3, only moderate or diffuse staining was observed. Low-grade
      parosteal and periosteal osteosarcomas showed low or undetectable levels of TGF
      beta 1, while TGF beta 2 and -3 were moderately or diffusely expressed. Finally,
      three dedifferentiated parosteal osteosarcomas were diffusely positive for TGF
      beta 1, -2, and -3 in the high-grade component, while in the low-grade component,
      available for analysis in two of these cases, TGF beta 1 was demonstrated in a
      few neoplastic cells, and TGF beta 2 and -3 maintained a diffuse distribution.
      Statistical analysis of these data showed that high-grade osteosarcomas had a
      significantly higher expression of TGF beta 1 than low-grade osteosarcomas, while
      levels of TGF beta 2 and -3 were comparable in the two groups (p < 0.001; p =
      0.3; p = 0.3, respectively; Fisher's exact test). Similarly, mRNA levels of TGF
      beta 1 detected by in situ hybridization were significantly higher (p = 0.04,
      Fisher's exact test) in high-grade osteosarcoma variants, while no differences
      were found for TGF beta 2 and -3 mRNA (p = 1.0; p = 0.2, respectively; Fisher's
      exact test). In addition, mRNA analysis performed by RT-PCR in seven cases (five
      high-grade and two low-grade osteosarcomas) confirmed the presence of high levels
      of TGF beta 1 in high-grade osteosarcomas, while low-grade tumours had low or
      absent mRNA expression. In conclusion, this positive association suggests that
      TGF beta 1 may be involved in determining the aggressive clinical behaviour of
      high-grade osteosarcomas.

PMID- 9771483
TI  - Heparan sulphate proteoglycan expression in human primary liver tumours.
AB  - Heparan sulphate proteoglycans (HSPGs) play important biological roles in cell
      matrix adhesion processes and are essential regulators of growth factor actions
      (e.g., as co-receptor for hepatocyte growth factor). Since in liver
      carcinogenesis, interactions between cells, the matrix, and growth factors play a
      major role, the aim of this study was to investigate whether the distribution
      pattern of HSPGs is altered in human primary liver tumours. Twenty-two primary
      liver tumours and five normal liver biopsies were studied, using specific
      monoclonal antibodies against syndecans-1, -2, -3, and -4; glypican; perlecan;
      and heparan sulphate chains. Cholangiocarcinomas as well as hepatocellular
      carcinomas showed an altered immunoreactivity pattern of the different HSPGs in
      comparison with normal liver parenchyma, probably reflecting the growth
      regulatory roles of HSPGs. Intracellular positivity for integral membrane HSPGs
      syndecan-1 and especially syndecan-4 was a constant finding in most tumours,
      suggesting increased synthesis or internalization of these HSPGs. Syndecan-3 and
      perlecan expression in tumours was found in an expected distribution pattern. The
      strong reactivity for syndecan-3 and perlecan in tumoral stromal vessels might
      suggest a role for these HSPGs in tumoral angiogenesis. In addition, perlecan
      probably exerts its known growth factor reservoir function also in the stroma of
      primary liver tumours.

PMID- 9771484
TI  - Anti-hepatocyte growth factor antibody inhibits hepatocyte proliferation during
      liver regeneration.
AB  - In vitro studies have shown hepatocyte growth factor (HGF) to be a potent mitogen
      for hepatocytes. Direct evidence of a mitogenic role in vivo was sought by
      inhibiting HGF activity, using continuous administration of neutralizing antibody
      to rats which had a stimulus for liver regeneration. Alzet osmotic mini-pumps,
      administering a constant supply of anti-HGF monoclonal antibody (clone D9), were
      inserted intraperitoneally into male Wistar rats; an irrelevant isotypical
      antibody was administered to controls. Forty-five animals received an
      intragastric bolus of 40 per cent carbon tetrachloride (CCl4) and groups of three
      test and control animals were killed at 24 h intervals for 7 days. Treatment with
      anti-HGF monoclonal antibody significantly inhibited the levels of
      immunodetectable HGF in the sera of rats following CCl4 administration. In
      comparison with controls, hepatocyte proliferation as assessed by
      bromodeoxyuridine labelling in anti-HGF-treated animals was significantly
      inhibited at 24 h (P < 0.001), 48 h (P < 0.001), and 96 h (P < 0.05) post-CCl4
      administration. In contrast, sinusoidal cell proliferation was not significantly
      different from controls at any time point. Inhibition of the parenchymal
      proliferative response to acute CCl4-induced liver injury by the in vivo
      neutralization of HGF provides direct evidence that this growth factor plays an
      important role in liver regeneration following necrosis.

PMID- 9771485
TI  - Co-expression of p53 and MDM2 in human atherosclerosis: implications for the
      regulation of cellularity of atherosclerotic lesions.
AB  - Atherosclerosis is a fibroproliferative disease of the arterial intima. It was
      recently found that wild-type p53 (wt p53) accumulates in human atherosclerotic
      tissue. Wt p53 is a cell cycle regulator involved in DNA repair, DNA synthesis,
      cell differentiation, and apoptosis and might therefore make an important
      contribution to the cellularity of atherosclerotic plaques. The product of the
      MDM2 gene is a nuclear protein which forms a complex with p53, thereby inhibiting
      the negative regulatory effects of wt p53 on cell cycle progression. In order to
      address a potential role of the interaction of p53 with MDM2 for the regulation
      of cellularity in atherosclerotic tissue, 22 carotid atheromatous plaques from
      patients undergoing endarterectomy were studied to determine the presence of p53
      immunoreactivity (IR), MDM2 IR, cell proliferation as evidenced by MIB1/Ki-67 IR
      and DNA fragmentation by in situ terminal transferase-mediated dUTP 3' end
      labelling (TUNEL), as a marker for apoptosis. p53 IR localized to areas with
      evidence of chronic inflammation (22/22) and was observed in virtually all cell
      types in 68.79 +/- 7.51 per cent of the nuclei. p53 staining in the control
      tissue from human internal mammary arteries was present in 0.2 +/- 0.29 per cent
      of the cells (P < or = 0.002). MDM2 IR was present in all cases (22/22) in
      macrophages and smooth muscle cells (SMCs) in 60.53 +/- 8.32 per cent of the
      nuclei (controls: 0.8 +/- 0.65 per cent, P < or = 0.002) and co-localized with
      p53 IR as shown by examination of adjacent sections and by double
      immunofluorescence labelling. Importantly, co-immunoprecipitation and western
      blot analysis revealed that p53 and MDM2 were physically associated, indicating
      that MDM2-p53 complex formation takes place in vivo in human atherosclerotic
      tissue. Positive TUNEL staining and MIB1/Ki-67 IR present in 3.01 +/- 1.27 per
      cent of the nuclei (controls: 0 per cent, P < or = 0.002) localized to the same
      plaque compartments as p53 IR and MDM2 IR. Thus, the fate of cells with p53
      accumulation may depend on the interaction and the stoichiometry of the p53 and
      MDM2 proteins. Cells were indeed found with strong p53 accumulation and nuclear
      morphology typical for apoptosis and there were a few MIB1/Ki-67-positive cells
      with co-expression of MDM2, indicating a possible role for MDM2 in reversing the
      negative regulatory effects of p53 for cell cycle progression. The nuclear co
      localization of p53 IR with MDM2 IR and the co-immunoprecipitation assay indicate
      the presence of p53-MDM2 complex formation in vivo in human atherosclerotic
      tissue. The destiny of individual p53 and MDM2-co-expressing cells either to
      undergo p53-dependent apoptosis or to re-enter the cycle of cell proliferation
      may depend on the relative ratios of the two proteins. p53 and MDM2 may therefore
      play an important role in regulating cellularity and inflammatory activity in
      human atherosclerotic plaques.

PMID- 9771486
TI  - High expression of endothelial nitric oxide synthase in plexiform lesions of
      pulmonary hypertension.
AB  - The pathogenesis of pulmonary hypertension (PH) remains poorly understood.
      Vasoconstriction, although likely to be a major factor in the disease, varies
      between patients and studies of a variety of vasoactive substances have sometimes
      yielded conflicting results. Amongst these substances, alteration of the nitric
      oxide (NO) system has been cited as a possible pathogenic factor but both
      reduction and elevation of the expression of endothelial NO-synthase (eNOS) have
      been reported in pulmonary vessels. The present study has used
      immunocytochemistry with well-characterized antibodies to eNOS to investigate its
      expression in lung tissue taken at transplantation from 44 patients with PH (22
      primary, 22 secondary) and 12 non-hypertensive controls. Semi-quantitative
      assessment showed that although the levels of eNOS expression in pulmonary
      vessels were variable within both hypertensives and controls, a statistically
      significant (P < 0.01) reduction of immunoreactivity was found in small
      arterioles from hypertensives compared with controls. In contrast, consistently
      strong expression of eNOS was seen in the endothelium of plexiform lesions in
      both the primary and the secondary PH patients. Although a decrease in the NO
      system of patients with PH has been reported, these findings show a distinct
      regional distribution of the enzyme with particularly high levels in plexiform
      lesions, a previously unreported observation, and offer a new perspective on the
      disease and on the evaluation of possible novel therapeutic approaches.

PMID- 9771487
TI  - Collagenase and gelatinase activities in bronchoalveolar lavage fluids during
      bleomycin-induced lung injury.
AB  - Basement membrane degradation can be indicative of tissue injury, but the process
      may also release matrix-bound cytokines to stimulate cell regeneration. To
      investigate this process, acute lung injury was induced in rats by intratracheal
      bleomycin and animals were killed from 3 days to 8 weeks later. The lungs were
      lavaged with saline to collect bronchoalveolar lavage (BAL) fluid and cell
      proliferation was assessed by pulse incorporation of tritiated thymidine.
      Bleomycin induced rapid inflammation with increased cell numbers and protein
      levels in BAL. Collagen degradation products were also increased in BAL fluid
      from 3 days to 4 weeks. Incubating samples of BAL fluid with radiolabelled
      collagens I and IV showed that high levels of activity, particularly for the
      degradation of type IV collagen, were present as early as 3 days post-bleomycin
      and persisted over the 8-week period. Zymograms demonstrated the highest level of
      gelatinase A (MMP-2) activity in BAL fluid in the first 2 weeks after bleomycin.
      Coincident with peak basement membrane degradative activity was the onset of a
      phase of epithelial cell proliferation, as measured by labelled nuclei in
      autoradiographs. The results show that enzymes capable of degrading the alveolar
      basement membrane are secreted early in the lung injury phase and that their
      presence in BAL fluid can be used as a measure of alveolar wall damage. It is
      possible that this enzyme action may release bound cytokines from the basement
      membrane, since maximal gelatinase activity correlates with alveolar epithelial
      cell proliferation.

PMID- 9771488
TI  - Bafilomycin A1 induces apoptosis in the human pancreatic cancer cell line Capan
      1.
AB  - Bafilomycin A1, a specific inhibitor of vacuolar type H(+)-ATPase, can inhibit
      the growth of a variety of cultured cells in a dose-dependent manner, but its
      mechanism is unclear. The aim of this study was to examine whether bafilomycin A1
      inhibits the growth of Capan-1 human pancreatic cancer cells through apoptosis.
      The effect of bafilomycin A1 on tumour growth in vitro and in vivo was examined
      using an MTT assay and an in vivo tumour model. The presence or absence of
      apoptosis was determined by morphology and DNA analysis of tumour cells. The
      concentration of bafilomycin A1 for 50 per cent inhibition of cell viability
      during 72 h by the MTT assay was 5 nm. In DNA analysis, a ladder of fragmented
      DNA was detected in Capan-1 cells treated with bafilomycin A1 at concentrations
      greater than 10 nm for 24 h. Nude mice bearing a xenografted Capan-1 cell line
      tumour received 4 weeks of bafilomycin A1 (1.0 mg/kg per day). This treatment
      significantly inhibited tumour growth compared with controls after 21 days (P <
      0.05). Histopathological examination of tumour cells in the treated group
      demonstrated signs of apoptosis with chromatin condensation and cell shrinkage.
      These observations suggest that bafilomycin A1 inhibits the growth of Capan-1
      human pancreatic cancer cells through apoptosis.

PMID- 9771489
TI  - Microwave irradiation lowers immunohistological detection thresholds for p53
      protein in squamous epithelium from non-neoplastic oesophagus.

PMID- 9771490
TI  - Time for evidence-based screening?

PMID- 9771491
TI  - The Bournewood case and its implications for health and social services.

PMID- 9771492
TI  - Dying in the dark: sunshine, gender and outcomes in myocardial infarction.
AB  - We report a natural experiment that took place in a cardiac intensive care unit
      (CICU). We had been alerted to the possibility that sunny rooms would be
      conducive to better outcomes by our findings in the psychiatric unit, and by
      reports that depressed cardiac patients did less well than those in normal mood.
      The 628 subjects were patients admitted directly to the CICU with a first attack
      of myocardial infarction (MI). Outcomes of those treated in sunny rooms and those
      treated in dull rooms were retrospectively compared for fatal outcomes and for
      length of stay in the CICU. Patients stayed a shorter time in the sunny rooms,
      but the significant difference was confined to women (2.3 days in sunny rooms,
      3.3 days in dull rooms). Mortality in both sexes was consistently higher in dull
      rooms (39/335 dull, 21/293 sunny). We conclude that illumination may be relevant
      to outcome in MI, and that this natural experiment merits replication.

PMID- 9771493
TI  - Neck and other muscle pains in autonomic failure: their association with
      orthostatic hypotension.
AB  - Neck pain in the suboccipital and paracervical region ('coathanger'
      configuration) is often reported by patients with autonomic failure and
      orthostatic hypotension. The frequency of this pain, along with pains in the
      buttock and calf regions, was determined by questionnaire in two major groups
      with primary chronic autonomic failure--pure autonomic failure (PAF) and multiple
      system atrophy (MSA). Comparisons were made with Parkinson's disease, cerebellar
      degeneration and other disorders in which neurological symptoms overlap but in
      which there was neither autonomic failure nor orthostatic hypotension. Neck pain
      was present in 93% of patients with PAF, 51% of patients with MSA and 38-47% of
      the non-autonomic groups. Buttock pain was present in smaller but similar
      proportions (8-19%) of each group, like calf pain (23-37%). Neck pain in PAF and
      MSA differed from that in the other groups in being relieved by sitting or lying
      flat and in being associated with factors that lower blood pressure in these
      patients. Buttock pain was posturally related in PAF and MSA; for calf pain there
      was no difference between groups. Neck pain was related to the degree of
      orthostatic hypotension; in PAF patients, whose postural blood-pressure fall was
      greater than that in MSA, there was a greater frequency of neck pain.

PMID- 9771494
TI  - Targeting of dornase alpha therapy in adult cystic fibrosis.
AB  - Although dornase alpha (recombinant human DNase) can thin the viscid pulmonary
      secretions of cystic fibrosis (CF), clinical trials in groups of unselected
      patients have shown only modest average improvements in pulmonary function. The
      product is very expensive, so in conjunction with purchasers we designed
      selection criteria and a protocol for a 2-week trial to target CF individuals who
      might gain most benefit. Treatment was to be continued in those showing > or =
      10% improvement in pulmonary function. Those who had a trial of dornase alpha
      were followed up for 2 years. Of 25 patients who had a 2-week trial of dornase
      alpha, 17 met the criteria for continuation (average gain in forced expiratory
      volume 37%). The 11 of these who were still alive at 2 years had a greater
      initial average FEV1 improvement than those who had died (45% versus 22%), and
      still had an average improvement of 31% at 2 years. The 8 patients who did not
      meet the criteria for continuation were older and had required fewer intravenous
      antibiotic courses. All these were alive at 2 years with unchanged clinical
      indices. This method of selection for dornase alpha treatment allows targeting to
      those who gain most benefit without disadvantaging the remaining patients.
      Furthermore, production of such guidelines in conjunction with purchasers
      obviates funding difficulties and allows rational prescribing.

PMID- 9771495
TI  - Screening instruments for psychiatric morbidity in chronic fatigue syndrome.
AB  - Physicians require a screening instrument to detect psychiatric disorders in
      patients with chronic fatigue syndrome (CFS). Different threshold scores on the
      Hospital Anxiety and Depression scale (HAD) and the mental health scale of the
      Medical Outcome Survey (MOS) were compared with two gold standards for the
      presence or absence of psychiatric disorder, standard diagnostic criteria (DSM
      III-R) and a threshold score for the number of psychiatric symptoms at a
      standardized psychiatric interview (Revised Clinical Interview Schedule total cut
      off score of 11/12). They were compared by use of validating coefficients and
      receiver operating characteristics in 136 consecutive CFS medical outpatients.
      The HAD scale at cut-off of 9/10 was a valid and efficient screening instrument
      for anxiety and depression by comparison with both gold standards. The MOS mental
      health scale at its recommended cut-off score of 67/68 yielded too many false
      positives to be recommended as a psychiatric screening instrument in CFS
      patients.

PMID- 9771496
TI  - Quality of medical information on the Internet.

PMID- 9771497
TI  - Do doctors read forms? A one-year audit of medical certificates submitted to a
      crematorium.
AB  - To determine the thoroughness and accuracy with which medical certificates for
      cremation are completed, a record was made, during normal processing of the
      documents, of the number of questions that were not answered or answered wrongly,
      or in which clarification was required. Of 835 sets of forms only 346 (41%) were
      completed sufficiently accurately for the cremation to proceed without further
      enquiry. Junior doctors contributed the most errors but general practitioners and
      consultants also contributed large numbers of errors. Doctors ought to be far
      more accurate and thorough in completing cremation certificates than were those
      audited here. The results cast doubt on the reliability of information supplied
      on other forms. In view of the high frequency of poorly completed forms, review
      by a medical referee remains essential.

PMID- 9771498
TI  - Triage of back pain by physiotherapists in orthopaedic clinics.
AB  - In 1994 we described a system whereby certain patients with back pain, on
      referral to an orthopaedic clinic, were seen first by a physiotherapist who
      referred on only the problem cases and those in need of surgery ('triage'). This
      practice has grown rapidly but there have been difficulties. To clarify these we
      have carried out a postal questionnaire. The results reveal similar practices in
      most centres but some discrepancies that are cause for concern. These relate to
      the workload of the physiotherapist, informed consent, supervision and
      accountability, the type of cases seen and not least the stresses on the
      physiotherapist. We believe the triage system has many benefits, but if it is not
      to be derailed the issues of concern must be addressed and the posts properly
      structured.

PMID- 9771499
TI  - Liaison psychiatrists in the accident and emergency department.

PMID- 9771500
TI  - Psammoma bodies on routine cervical smear.

PMID- 9771501
TI  - Survival of the Judet hip prosthesis.

PMID- 9771502
TI  - Median nerve palsy after high brachial angiography.

PMID- 9771503
TI  - Frey's syndrome without hyperhidrosis.

PMID- 9771504
TI  - Dorothy Wordsworth's mental illness.

PMID- 9771505
TI  - The 'boom' in complementary medicine.

PMID- 9771506
TI  - Health statistics on the Internet.

PMID- 9771507
TI  - Haemophilia: does the future lie in replacement therapy or auto-supply?

PMID- 9771509
TI  - Healing and expectation.

PMID- 9771508
TI  - The bittersweet demise of Herod the Great.

PMID- 9771510
TI  - Dementia care: nearly a seamless service or merely an unseemly squabble between
      physicians and psychiatrists.

PMID- 9771511
TI  - Risks or remedies? Safety aspects of herbal remedies in the UK.

PMID- 9771512
TI  - Contraceptive use in a rural general practice.
AB  - All women aged 20-49 in a general practice were sent a questionnaire about their
      reproductive health, and 72% responded. 78% of respondents were using a method of
      fertility control. More than a quarter of women were obtaining their
      contraceptive supplies (condoms especially) from non-medical outlets. Knowledge
      of the existence of emergency contraception was high (83%). The general
      practitioner (GP) was the most popular source of contraceptive supplies for those
      aged under 40 years and more than four-fifths of women said that they would
      rather turn to their GP than to other sources for future contraceptive advice.

PMID- 9771513
TI  - Ambulatory blood pressure monitoring for hypertension in general practice.
AB  - Ambulatory blood pressure monitoring (ABPM) is being increasingly used in general
      practice. There is at present little published evidence regarding the clinical
      utility of ABPM in the care of patients with established hypertension in this
      setting. We examined this issue by undertaking ABPM in a group of patients with
      established hypertension. 40 patients (aged 33-60 years) currently being treated
      for hypertension were randomly selected from a general practice list and
      underwent a single 24-hour ABPM study. ABPM values were compared with clinic
      blood pressure (CBP) values obtained on the day of monitoring together with
      previous readings taken by the general practitioner (GP). In the case of mean
      arterial pressure, 24-hour, awake and asleep ABPM values were found to
      underestimate CBP values by 14 mmHg (95% confidence interval 11-16 mmHg), 9 mmHg
      (95% C16-12 mmHg) and 24 mmHg (95% CI 21-27 mmHg), respectively. When used to
      classify blood pressure control, ABPM values produced equivalent results to CBP
      except by the criterion of BP load, for which 24-hour ABPM showed a higher rate
      of unsatisfactory control. 5 patients classified by CBP to have satisfactory BP
      control according to current international guidelines were found to have
      unsatisfactory BP control by ABPM. This study demonstrates the potential value of
      ABPM in patients with essential hypertension in a general practice setting. ABPM
      provided information over and above that obtained by CBP in a substantial
      proportion of patients.

PMID- 9771515
TI  - Medical education on the World Wide Web.

PMID- 9771514
TI  - Better drug history taking: an assessment of the DRUGS mnemonic.
AB  - To improve drug history taking before anaesthesia, we have previously suggested a
      checklist with the mnemonic DRUGS (Doctor, Recreational, User, Gynaecological,
      Sensitivities). We have now tested this mnemonic in 1053 patients admitted for
      surgery, comparing the results with the information obtained in the original
      clerking. Use of the mnemonic yielded additional information in 621 patients
      (59%). Drugs which had gone unrecorded in routine clerking were detected in 24%
      of patients on medication. Of 199 patients with high alcohol intake, this feature
      had been recorded in only 38 (19%). Unprescribed medicines, being taken by 158,
      had been noted in only 31 (20%). Of women taking oral contraceptives or hormone
      replacement therapy, more than two-thirds had not given this information.
      Sensitivities had been recorded accurately in 100 patients but the mnemonic
      yielded relevant information in a further 85. On this evidence, use of the simple
      DRUGS mnemonic improves drug history taking in anaesthetic practice.

PMID- 9771516
TI  - 'What should I do if the baby stops breathing'?

PMID- 9771517
TI  - Diarrhoea in two worlds: the messages of Ballard and Newman.

PMID- 9771518
TI  - Interdisciplinary relationships.

PMID- 9771519
TI  - Calmanization of general surgery.

PMID- 9771520
TI  - Pulmonary hypertension resulting from upper airways obstruction in Down's
      syndrome.

PMID- 9771521
TI  - Facial paralysis after a road traffic accident.

PMID- 9771522
TI  - Acute arterial thrombosis after a long-haul flight.

PMID- 9771523
TI  - Epileptic seizures due to cerebral artery aneurysm.

PMID- 9771524
TI  - A lateral view: the news reporter and conflict recovery.

PMID- 9771525
TI  - Phthiriasis: the riddle of the lousy disease.

PMID- 9771526
TI  - Caleb Hillier Parry 1755-1822: a notable provincial physician.

PMID- 9771527
TI  - Back pain in pregnancy.

PMID- 9771528
TI  - Confusion of roles.

PMID- 9771529
TI  - Gleb von Anrep.

PMID- 9771530
TI  - Technological medicine and the elderly.

PMID- 9771531
TI  - Popularity of alternative medicine.

PMID- 9771532
TI  - Palpitation: brain, heart and 'spirits' in the seventeenth century.

PMID- 9771533
TI  - Osteoarthritis.

PMID- 9771534
TI  - Rheumatoid arthritis. A paradigm of inflammatory disease of the musculoskeletal
      system.

PMID- 9771535
TI  - Joint infection.

PMID- 9771536
TI  - Surgery and joint replacement for joint disease.

PMID- 9771537
TI  - Osteoporosis 2000-2010.

PMID- 9771538
TI  - Epidemiology of low back pain.

PMID- 9771539
TI  - Spinal disorders. Basic science.

PMID- 9771540
TI  - Degenerative conditions of the spine. Current diagnostic procedures and treatment
      modalities.

PMID- 9771541
TI  - Severe limb injuries.

PMID- 9771542
TI  - Victims of war. Surgical principles must not be forgotten (again)!
AB  - Severe injuries to the limbs are common in wars and natural disasters, and most
      of them occur in developing countries with weak health-care systems. The
      International Committee of the Red Cross (ICRC) has gained a vast amount of
      experience in treating the war-wounded in this context. Basic principles for
      wound management, safe and simple methods for fracture-holding and amputation
      techniques adapted to missile and explosive injuries have proven successful. More
      than 81,000 amputees have been fitted with artificial limbs in ICRC workshops
      since 1979, but the needs are far greater. In an attempt to limit the effects of
      war, the ICRC promotes compliance with international humanitarian law, supports
      preventive activities such as the campaign to ban anti-personnel landmines, and
      strives to raise awareness of the implications of fast-developing weapon
      technologies.

PMID- 9771543
TI  - The economic impact of musculoskeletal disorders.

PMID- 9771544
TI  - Musculo-skeletal diseases.

PMID- 9771545
TI  - The Bone and Joint Decade 2000-2010. Inaugural meeting 17 and 18 April 1998,
      Lund, Sweden.
AB  - The increasing impact of bone and joint disorders on patients and healthcare
      systems, and an awareness that resources need to be more efficiently used, led to
      arrangements for a Consensus Meeting. This was held in Sweden in April 1998 and
      ended in an agreement to launch a Decade of Bone and Joint from 2000 to 2010. The
      aims of the Decade will be to raise awareness of the suffering and cost to
      society of musculoskeletal disorders such as joint diseases, osteoporosis, spinal
      disorders and severe trauma, and encourage research and development throughout
      the world.

PMID- 9771550
TI  - Effects of beta-carotene, retinal, riboflavin, alpha-tocopherol and vitamins C
      and K1 on sister-chromatid exchanges induced by 3-amino-1-methyl-5H-pyrido[4,3
      b]indole (Trp-P-2) and cyclophosphamide in human lymphocyte cultures.
AB  - The vitamins and related compounds cited in the title were investigated for their
      abilities to modulate sister-chromatid exchanges (SCEs) induced by Trp-P-2 or
      cyclophosphamide (CP) in human peripheral lymphocyte cultures in the presence of
      an exogenous metabolizing system from rat liver. When inducer and test substances
      were given simultaneously, beta-carotene, retinal and alpha-tocopherol caused a
      dose-dependent decrease of SCE frequencies induced by Trp-P-2 and CP. Vitamin K1,
      however, brought about an identical effect with Trp-P-2 only, while with CP an
      initial decrease of SCEs was followed by a statistically significant re-increase
      at higher concentrations. Vitamin C was ineffective against Trp-P-2, but caused
      an overall increase of SCEs induced by CP. When blood cultures were preincubated
      with vitamins before the addition of CP or Trp-P-2, basically identical effects
      were observed with beta-carotene, retinal, alpha-tocopherol, vitamin K1 and
      vitamin C. Riboflavin decreased SCEs induced by Trp-P-2 in all treatment
      schedules, although statistically confirmed minima were observed in the dose
      response curves, except in post-treatment experiments. On the other hand,
      riboflavin only reduced SCEs induced by CP when it was preincubated with
      lymphocytes. When vitamins were applied in a post-treatment schedule after
      removal of Trp-P-2 or CP, again, basically identical results against both
      genotoxins were observed with beta-carotene, retinal and alpha-tocopherol with
      vitamin K1, however, only with respect to Trp-P-2, and with vitamin C only with
      respect to CP. In the post-treatment schedule, vitamin K1 caused a decrease of
      SCE frequencies induced by CP, and vitamin C a decrease of SCEs induced by Trp-P
      2.

PMID- 9771551
TI  - Distribution and excretion of radiolabelled tert-butylhydroquinone in Fischer 344
      rats.
AB  - Uniformly 14C-ring-labelled tert-butylhydroquinone (TBHQ) was diluted with non
      radioactive TBHQ and administered orally (for excretion studies) to Fischer 344
      rats. An average of 72.9% and 10.6% of the administered radioactivity was
      recovered in the urine and faeces, respectively, of male rats, and 77.3% and 8.2%
      in the urine and faeces, respectively, of female rats in 4 days. No significant
      sex-related differences were found in either excretion, tissue distribution or
      urinary metabolites of TBHQ-derived radiolabel. For distribution studies,
      intraperitoneal doses were administered to female rats, and tissue levels of
      radiolabel were determined at various times after dosing. The parent compound
      quickly disappeared from tissue in vivo. The highest concentrations of radiolabel
      were found in the liver and kidneys. The urinary metabolites consisted of
      conjugated TBHQ and unidentified polar substance(s).

PMID- 9771552
TI  - Subchronic toxicity study of tetrahydroisohumulone and hexahydroisohumulone in
      the beagle dog.
AB  - Hops and hop extracts are approved and widely used bittering agents in the
      brewing of beer. During recent years, preisomerized alpha hop acids and reduced
      preisomerized alpha hop acids have been introduced as effective and economical
      bittering agents that may be added late in the brewing process. Although hops
      have been used for centuries, there are few studies in the literature on the
      safety of this ingredient. The study herein was conducted to determine the
      effects associated with subchronic oral administration of the reduced
      preisomerized hop acids, hexahydroisohumulone and tetrahydroisohumulone, in the
      dog. The results show that these materials are generally well tolerated in the
      dog. At high dose levels they induce vomiting, and much of the material
      administered was excreted in the faeces. The no-observed-adverse-effect level
      (NOAEL) of the compounds were 50 and 100 mg/kg body weight, respectively.
      Consumption of these ingredients by adult humans drinking 1 litre of beer daily
      is less than 0.25 mg/kg body weight; their use is thus associated with wide
      safety margins.

PMID- 9771553
TI  - Dimethylamine formation in the rat from various related amine precursors.
AB  - Dimethylamine is the immediate precursor of dimethylnitrosamine, a known potent
      carcinogen in a wide variety of animal species. Although small amounts of
      dimethylamine are ingested directly, the major dietary source is believed to be
      via choline and related materials. Owing to quantitative recoveries following
      oral administration, urinary dimethylamine levels provide good overall measures
      of body exposure. The oral administration of equimolar amounts (1 mmol/kg body
      weight) of potential amine precursors to male Wistar rats produced only small
      increases in urinary dimethylamine after choline (+ 11%; 0.60 +/- 0.36% dose),
      dimethylaminopropanol (+ 32%; 1.49 +/- 0.30% dose), dimethylaminoethyl chloride
      (+ 110% 5.38 +/- 1.72% dose) and trimethylamine (+ 51%; 1.6 +/- 0.80% dose)
      input, whereas significantly larger increases were found following trimethylamine
      N-oxide ingestion (+ 355%; 12.93 +/- 1.13% dose; t-test, P < 0.001). These data
      suggest that trimethylamine N-oxide is a major dietary source of dimethylamine,
      by direct conversion and not by sequential reduction (to trimethylamine) and
      demethylation, and that in this respect it is of greater importance, on a molar
      basis, than choline.

PMID- 9771554
TI  - Effect of a necrogenic dose of diethylnitrosamine on vitamin E-deficient and
      vitamin E-supplemented rats.
AB  - In order to evaluate the effects of a necrogenic dose of diethylnitrosamine (DEN)
      on vitamin E-deficient and vitamin E-supplemented rats, a single dose of the drug
      (200 mg/kg body weight) was injected intraperitoneally at the end of 10 weeks of
      treatment with the diets. The hepatic necrosis and lipoperoxidation provoked by
      DEN were evaluated 24, 48, 72 and 120 hours after the injection and were found to
      be more intense in the deficient group (thiobarbituric acid reactive substances
      (TBARS): 5.20 +/- 1.48 nmol/mg protein; necrosis volume: 68.99 +/- 8.36%; P <
      0.05) during the second period. Also, in the same group and during the same
      period, mean plasma and hepatic vitamin E concentrations and mean liver
      glutathione concentration were the lowest detected, suggesting the occurrence of
      antioxidant consumption due to the toxic action of DEN. In contrast to vitamin E
      deficiency, which permitted the drug to exert stronger toxic effects, 20-fold
      supplementation with vitamin E did not provide additional protection against the
      lipoperoxidation and necrosis provoked by DEN (P < 0.05). The results suggest
      that other mechanisms in addition to lipoperoxidation provoked by free radicals
      originating from the metabolism of nitrosamines by the cytochrome P-450-dependent
      enzymatic system may be involved in the hepatotoxic action of these substances.

PMID- 9771555
TI  - Genotoxicity of sennosides on the bone marrow cells of mice.
AB  - Preparations of a number of plants which contain hydroxyanthraquinones as active
      constituents are used worldwide for their laxative effect. Anthraquinone
      glycosides of Cassia angustifolia and C. fistula were investigated for their
      ability to induce a clastogenic effect on the bone marrow cells of Swiss albino
      mice. The endpoints screened were chromosomal aberrations and frequency of
      aberrant cells. Oral exposure to doses of these anthraquinones and their
      equivalent amount in leaf and pod extracts did not induce significant numbers of
      chromosomal aberrations or aberrant cells. The results indicate that
      anthraquinone sennoside B and rhein are weakly genotoxic.

PMID- 9771556
TI  - Chronic alcoholization in rats by free-choice ingestion of a hydroalcoholic
      solution.
AB  - The present work addresses a schedule designed to render rats alcoholic by
      offering them free access to a 20% (v/v) ethanol solution over 6 weeks. A solid
      diet and water (for controls) were fully available ad lib. in the animals' cages.
      The treatment was observed to achieve some effects suitable for the chronic
      alcoholization of rats: (1) Ethanol furnished the 36% of the calories of the diet
      of ethanol-treated rats; (2) The daily ethanol intake achieved was 12.05 +/- 1.18
      g ethanol/kg weight; (3) The morning blood ethanol level was 0.45 g/litre; (4)
      Ethanol-treated rats deprived of ethanol showed several withdrawal symptoms.
      These results agree with those obtained by standard liquid diets, suggesting that
      the current protocol can be used to achieve a status of chronic alcoholization in
      rats.

PMID- 9771557
TI  - Effects of the trichothecene mycotoxin T-2 toxin on neurotransmitters and
      metabolites in discrete areas of the rat brain.
AB  - T-2 toxin has been shown to affect the central nervous system. Only recently have
      attempts been made to characterize the neurochemical perturbations associated
      with T-2 intoxication. To examine the effect of T-2 on regional brain biogenic
      monoamines and selected metabolites, male rats were dosed orally with T-2 toxin
      in corn oil at 0.1, 1.0 or 2.5 mg/kg body weight. At 2, 6 and 10 hr post-dosing,
      rats were killed, brains were collected and stored at -80 degrees until analysed.
      Brain nuclei, including nucleus raphe magnus, paraventricular nucleus, locus
      coeruleus, substantia nigra, medial forebrain bundle, nucleus accumbens and
      olfactory tubercle, were analysed. T-2 treatment increased 5-hydroxy-3
      indoleacetic acid and serotonin throughout the brain, and produced a transient
      increase in norepinephrine in the nucleus raphe magnus and a temporary decrease
      in the substantia nigra. Regional dihydroxyphenylacetic acid concentration was
      affected, with increased DOPAC observed in the locus coeruleus, medial forebrain
      bundle and paraventricular nucleus of the hypothalamus, and decreased DOPAC in
      the olfactory tubercles. No regional changes in epinephrine or dopamine were
      observed. Few treatment differences were observed, with the 0.1 mg/kg body weight
      T-2, 2% of the LD50, significantly affecting brain monoamines. It had been
      suggested that neurological manifestations of T-2 toxin are the result of brain
      hypoxia; however, the altered brain monoamine profile observed at doses that do
      not alter heart function, suggests the brain is a primary site of trichothecene
      action.

PMID- 9771558
TI  - Effect of T-2 toxin on blood-brain barrier permeability monoamine oxidase
      activity and protein synthesis in rats.
AB  - Systemic exposure to T-2 toxin disrupts brain biogenic monoamine metabolism.
      Although the mechanisms underlying these neurochemical perturbations are unclear,
      we have suggested that they are a reflection of increased blood-brain barrier
      (BBB) permeability, or altered protein synthesis that affects brain enzyme
      activities. Accordingly, BBB permeability, in vitro protein synthesis and in
      vitro monoamine oxidase (MAO) activity were examined in rats after either acute,
      or 7-day exposure to T-2. Membrane permeability was assessed from the recovery of
      systemically administered [14C]mannitol and [14C]dextran with [3H]water as the
      diffusible reference, either 2 hr post-intraperitoneal (i.p.) injections of 0,
      0.2 and 1 mg T-2/kg body weight or following a 7-day exposure to diets containing
      0 and 10 ppm T-2. Protein synthesis, determined by [14C]leucine incorporation,
      and MAO activity, determined by H2O2 production, were observed either 2 hr post
      ip injection of 0 and 1 mg T-2/kg body weight or following a 7-day exposure to
      diets containing 0, 2.5 and 10 ppm T-2. Permeability increases were observed in
      all brain regions examined for mannitol, but not for dextran following T-2 i.p.
      The effect of dietary T-2 was more modest, affecting mannitol uptake in two brain
      regions, the cerebellum and pons plus medulla regions. Protein synthesis was
      significantly decreased by i.p. administration of T-2, while dietary treatment
      significantly reduced MAO enzyme activity. Collectively, the effect of T-2 toxin
      on BBB permeability, protein synthesis and MAO enzyme activity may account for
      the neurochemical imbalance observed in T-2 intoxication.

PMID- 9771559
TI  - Oral toxicity of bis(2-ethylhexyl) phthalate during pregnancy and suckling in the
      Long-Evans rat.
AB  - Bis(2-ethylhexyl) phthalate (DEHP) is a compound widely used in plastics
      technology to impart flexibility to rigid polymers. We sought to determine
      whether the oral exposure of female rats to DEHP during gestation and suckling
      produces alterations in the litter. Female rats were exposed to different
      concentrations of DEHP suspended in drinking water (32.5 and 325 microl/litre)
      from day 1 of pregnancy to day 21 after delivery. Pup body weight gain and
      kidney, liver and testes weight was measured at different times (21, 28, 35, 42
      and 56 days) after birth. Plasma concentrations of DEHP and histopathological
      alterations in kidneys, liver and testes were also studied. In addition, the
      ability of female pups (1 month of age) to perform a learned avoidance test, the
      'beam walking' test, was evaluated. Perinatal exposure to DEHP produced no
      statistically significant changes in the body weight gain of offspring.
      Conversely, it produced a significant decrease in kidney and testes relative
      weight (organ/body weight) with a significant increase in relative liver weight.
      Signs of histological damage in kidneys, liver, and particularly testes, were
      observed. Pups exposed perinatally to the highest concentration of DEHP elicited
      a significant increase in the time necessary to perform the beam walking test.

PMID- 9771560
TI  - Covalent binding of agaritine to DNA in vivo.
AB  - 14C-Ring-labelled agaritine was administered orally to eight C57BL/6 mice at a
      chemical dose of 7.5 mg and radioactive dose of 1.2 x 10(9) dpm/kg body weight.
      After 24 hr, the animals were killed and DNA from stomach, liver and kidneys was
      purified by a phenol-free method involving proteinase K digestion of chromatin
      and coprecipitated proteins, followed by hydroxylapatite chromatography, dialysis
      and precipitation with ethanol. An increase in radioactivity was found in DNA of
      all three organs examined. Stomach DNA had the highest levels: 160 and 30 dpm/mg
      DNA in males and females, respectively. Liver and kidney DNA both showed levels
      of approximately 1 dpm/mg, with no measurable gender differences. Expressed in
      the units of the covalent binding index (CBI), agaritine has a potency of 42 in
      mouse stomach in males and 8 in females. The CBI of agaritine in liver and kidney
      was 0.2-0.3 in both sexes. The genotoxic activity of agaritine is thus very weak.
      The cumulative lifetime cancer risk of agaritine consumption in mushrooms is
      estimated to lie at approximately 10(-5).

PMID- 9771561
TI  - Prevention of cyclophosphamide-induced micronucleus formation in mouse bone
      marrow by indole-3-carbinol.
AB  - Indole-3-carbinol (I3C) is a glucobrassicin derivative isolated from cruciferous
      vegetables. In this study, the protective effect of 13C is reported against
      cyclophosphamide (CP)-induced micronuclei formation in mouse bone marrow cells.
      The three test doses, namely 500, 250 and 125 mg/kg body weight of 13C provided
      protection when given 48 hr prior to the single ip administration of
      cyclophosphamide (50 mg/kg). The efficacy of the test doses of 13C was also
      evaluated using a lower dose of CP (25 mg/kg body weight). A significant
      inhibition in micronuclei formation was noticed with 13C at 250 and 125 mg/kg
      body weight dose. 13C could not induce micronuclei formation at the test doses
      500 and 250 mg/kg body weight. 13C, therefore seems to have a preventive
      potential against CP-induced micronuclei formation in Swiss mouse bone marrow
      cells.

PMID- 9771562
TI  - Short- and intermediate-term carcinogenicity testing--a review. Part 1: the
      prototypes mouse skin tumour assay and rat liver focus assay.
AB  - Carcinogenicity testing is by far the most expensive and time-consuming study
      type of toxicology. For many years, the lifetime exposure with the maximum
      tolerated dose in two rodent species has been the gold standard of
      carcinogenicity testing of pharmaceuticals. Major change was introduced by the
      Fourth International Conference on Harmonization in July 1997; a chronic rodent
      bioassay in one species and a short-term carcinogenicity assay are regarded as
      sufficient for registration. Such requirements provide the opportunity to
      redirect the vast resources previously spent on the lifetime study in the second
      species. Numerous experimental protocols for short- and intermediate-term
      carcinogenicity testing in many target tissues have been available for years. The
      first part of this review describes the basic principles of short- and
      intermediate-term carcinogenicity testing using the examples of the widely used
      mouse skin tumour assay and the rat liver foci assay. In the context of these
      experimental models, the discrimination and quantification of initiating and
      promoting activity and the use of preneoplastic lesions as endpoints in
      carcinogenicity testing are described. The review includes the limitations of the
      models with regard to the extrapolation from effects observed in animal
      experiments to a potential exposure of humans.

PMID- 9771563
TI  - Short- and intermediate-term carcinogenicity testing--a review. Part 2: available
      experimental models.
AB  - Numerous experimental protocols for short- and intermediate-term carcinogenicity
      assays have been available for many years. This paper surveys various of these
      test systems in rodents, fish species, non-vertebrates and avian embryos in ovo.
      The mouse skin tumour assay and the rat liver foci assay were used to introduce
      the basic concepts of short- and intermediate-term carcinogenicity testing in the
      previous part of the review. The focus of this second part of the review is on
      rodent assays for carcinogenicity testing in the lung, kidney, urinary bladder,
      pancreas, stomach, oral cavity, small intestine, colon, and on the possibility to
      combine several target organs in multi-organ models. The potential use of various
      fish species, non-vertebrates and hatching eggs for carcinogenicity testing is
      outlined and the advantages and limitations are discussed. This review also
      presents the problem of validation of any carcinogenicity test system and
      proposes a strategy for contemporary safety assessment of chemicals with regard
      to the detection and evaluation of carcinogenicity.

PMID- 9771564
TI  - Smokeless tobacco and oral cancer: an assessment of evidence derived from
      laboratory animals.
AB  - No carcinogenic activity was observed when snuff was inserted into the cheek
      pouch of the hamster or spread over the oral mucosa. This negative result was
      obtained in a number of experiments whether snuff was applied once only and left
      in place for several months or inserted repeatedly for up to 2 years. In the rat,
      a few tumours were observed when snuff was inserted into the artificial lip
      canal. The insertion appeared to cause a considerable reaction in the surrounding
      tissue so it is plausible to assume that trauma plays an important role in the
      development of these tumours. An extract of snuff applied to the oral mucosa of
      the rat did not produce any tumours, but an extract enriched by the addition of
      10 times the naturally-occurring amounts of NNN and NNK produced a few benign
      tumours at the site of application. A higher incidence of tumours was produced
      when an equivalent amount of an aqueous solution of these two nitrosamines was
      applied directly to the oral mucosa, suggesting, according to the authors, that
      snuff inhibits the carcinogenic activity of TSNAs. Initiation/promotion studies
      were carried out on snuff in the rat in order to explore further its carcinogenic
      potential. The results were consistent with the conclusion that snuff does not
      possess any promotional activity. No increase in tumour incidence was observed in
      mice when snuff was given in the diet at concentrations of 25% gradually
      decreasing to 5% in a 14 month study. A negative result was also obtained in the
      rat given snuff at a concentration of 5% for 18 months. In hamsters given snuff
      at a concentration of 20% for 2 years, forestomach tumours occurred. A comparable
      incidence of this type of tumour occurred in animals given 20% cellulose. The
      result of this study does not provide valid evidence of carcinogenicity. HSV and
      snuff applied orally in the hamster produced a high incidence of squamous cell
      carcinomas. The sustained high level of squamous cell hyperplasia generated by
      the experimental design could account for the development of these tumours.
      Despite the defects in some of the earlier studies, the sum total of this
      experimental work suggests that snuff is not carcinogenic to the oral mucosa of
      the hamster or the rat. It is also unlikely to cause tumours in other tissues in
      these species. These results give some degree of reassurance that snuff is not
      likely to be carcinogenic to the human oral mucosa. The interaction of snuff and
      HSV viruses is, at the moment, questionable and requires further investigation.

PMID- 9771566
TI  - Optimization of chemical shift selective suppression of fat.
AB  - Strategies to optimize flip angles for chemical shift selective fat suppression
      are discussed. Mathematical models for fat suppression in spoiled gradient
      recalled acquisition, spin echo, and RARE, which incorporate steady state
      conditions and multiple spectral components of fat, are developed. The optimal
      suppression flip angle is found to be larger than that determined with a single
      fat component model by more than 10 degrees due to contributions from unflipped
      components such as olefinic and glycerol protons that lie outside the suppression
      band.

PMID- 9771565
TI  - Effects of an enteral nutritional formula (ENF) administration containing or not
      containing supplemental fructooligosaccharides (FOS) in healthy human adults.

PMID- 9771567
TI  - A motion correction scheme by twin-echo navigation for diffusion-weighted
      magnetic resonance imaging with multiple RF echo acquisition.
AB  - In this paper, a series of diffusion-weighted fast spin-echo (FSE) sequences with
      a new motion correction scheme are introduced. This correction scheme is based on
      the navigator echo technique. Unlike conventional spin-echo imaging, motion
      correction for FSE is complicated by the phase oscillation between odd-numbered
      and even-numbered echoes and the complex phase relationship between spin echo and
      stimulated echo components. In our approach, incoherent phase shifting due to
      motion is monitored by consecutive acquisition of two navigator echoes, which
      provide information on both inter-echo and intra-echo train phase shifts.
      Applications to both phantom and in vivo studies are presented.

PMID- 9771568
TI  - Quantitative regional blood volume studies in rat myocardium in vivo.
AB  - Many pathophysiological processes in the myocardium are in close relation to
      changes of the regional blood volume and regional myocardial blood flow or
      perfusion. Only few methods exist to obtain quantitative values for these
      parameters. Quantitative regional blood volume (RBV) studies in rat myocardium
      are presented using snapshot fast low angle shot (FLASH) inversion recovery T1
      measurements with two different blood pool contrast agents, gadolinium
      diethylenetriaminopentaacetic acid (Gd-DTPA) albumin and Gd-DTPA polylysine. In
      contrast to previous attempts, each snapshot FLASH image acquisition was ECG
      triggered under breathhold conditions. To measure relaxation times shorter than a
      heart cycle, each T1 sequence was repeated two times with different delays
      between inversion pulse and first image acquisition. The experiments were
      performed on a Bruker Biospec 70/21 using a homogeneous transmitter coil and a
      circularly polarized surface receiver coil, a special ECG trigger unit, and a
      respirator that is controlled by the pulse program. Based on a fast exchange
      model RBVm maps were calculated from the relaxation time maps for different
      concentrations of the two blood pool contrast agents. A significant dependence of
      the RBVm values on blood T1 was found. This is in accordance with a model that
      has been developed recently relating the dependence of RBVm on T1 of blood to
      perfusion. For Gd-DTPA albumin, the application of the model to the experimental
      data yields realistic values for RBV and perfusion. The values, which are in
      accordance with literature data, were obtained at highest contrast agent
      concentrations i.e., lowest relaxation times of blood (ca. 200 ms).

PMID- 9771569
TI  - Quantification of intravascular and extravascular contributions to BOLD effects
      induced by alteration in oxygenation or intravascular contrast agents.
AB  - A simple model is presented that allows quantitative separation of the
      contributions of signals from water in blood and extravascular parenchyma due to
      changes in blood oxygenation, induced either by brain activation or by alteration
      of inspired oxygen. The separation is based on the progressive attenuation of the
      signals in the vasculature of different levels when bipolar field gradient pulses
      are applied. Diffusion-weighted spin-echo echo-planar imaging sequences were used
      to measure signal changes under various conditions in both animals and human
      volunteers. Normoxic-hyperoxic episodes were induced in rats before and after
      injection of a superparamagnetic iron oxide contrast agent. Signal changes
      produced by visual stimulation were measured in human volunteers, and in
      volunteers subject to alternating normoxic-hyperoxic episodes, and with
      administration of Gd-DTPA. Analysis of the results with our simple model suggests
      that the apparent diffusion coefficient increases and R2 (= 1/T2) decreases upon
      brain activation, with a large component from extravascular water related to the
      decrease in the blood deoxyhemoglobin concentration. Furthermore, this study
      suggests that apparent diffusion coefficient of the extravascular component alone
      may provide localization of neuronal activation.

PMID- 9771570
TI  - Quantification of the extraction fraction for gadopentetate across breast cancer
      capillaries.
AB  - To quantify the extraction fraction, E, for gadopentetate across tumor
      capillaries, R3230 adenocarcinomas were implanted in the mammary fat pads of
      seven rats. The value of E was determined by using a two-compartment tissue model
      in which the endothelial transfer coefficient, K(PS) (ml x min(-1) x cc(-1) of
      tissue), was estimated from the model fitted to changes in R1 relaxation time
      (deltaR1; s(-1)) measured by dynamic three-dimensional spoiled gradient recalled
      magnetic resonance imaging after injection of 0.1 mmol x kg(-1) of gadopentetate
      dimeglumine. The plasma flow rate through the tumor capillaries, Fp, (ml x min(
      1) x g(-1) of tissue), was independently measured with fluorescent microspheres.
      E could be calculated by the relationship, E = K(PS)/Fp. The mean E for
      gadopentetate in the R3230 tumor was 0.197 +/- 0.118 with a range of 0.123-0.454.
      The relatively small mean value of E for gadopentetate allows a fair
      approximation of the permeability surface area product by K(PS) in this R3230
      tumor model.

PMID- 9771571
TI  - 39K NMR measurement of intracellular potassium during ischemia in the perfused
      guinea pig heart.
AB  - The hyperfine shift reagent, TmDOTP5-, was used to resolve the 39K NMR resonances
      of intra- (Ki+) and extracellular (Ke+) potassium in isolated, perfused guinea
      pig hearts. [Ki+] as measured by 39K NMR was 25.9 +/- 10.3 mM, compared with
      114.4 +/- 10.8 mM as measured by atomic absorption spectroscopy (AAS) using
      TmDOTP5- as a marker of extracellular space. Thus, only approximately 23% of
      intracellular potassium was detected by 39K NMR using our experimental
      conditions. The area of the Ki+ signal increased during early ischemia then
      returned to baseline levels during reperfusion. In an effort to learn more about
      the Ki+ not detected by 39K NMR, hearts were perfused with a Rb+-enriched, K+
      depleted buffer for an extended period. This resulted in loss of the entire 39K
      NMR signal, and Ki+, as measured by AAS, decreased from approximately 60 to
      approximately 6 to 7 micromol/g wet weight. When K+-depleted hearts were
      subjected to global ischemia, a small 39K NMR signal reappeared, suggesting that
      at least a portion of the nonexchangeable Ki+ becomes detectable by NMR during
      ischemia. This newly visible K+ signal subsequently dissipated during reperfusion
      of ischemic hearts. We conclude that ischemia induces changes in the NMR
      visibility of 39K in perfused guinea pig hearts.

PMID- 9771572
TI  - Evidence of muscle BOLD effect revealed by simultaneous interleaved gradient-echo
      NMRI and myoglobin NMRS during leg ischemia.
AB  - The purpose of this work was to investigate the temporal relationship between
      intensity changes in T2*-weighted NMR images and tissue oxygen content, measured
      by myoglobin proton NMR spectroscopy, in the skeletal muscle. During an ischemic
      stress test, the calf muscles of five healthy volunteers were studied at 3 Tesla.
      An interleaved NMRI-NMRS sequence was used, which made it possible to record T2*
      weighted images and myoglobin spectra simultaneously. During ischemia, rapid
      changes in muscle signal intensity were observed on T2*-weighted images, which
      immediately preceded myoglobin desaturation. Bearing in mind the respective P50
      of hemoglobin and myoglobin, this observation clearly favored the hypothesis that
      hemoglobin desaturation was responsible for the changes in T2*. This
      interpretation was further supported by the temporal coincidence between the
      experimental NMR data and a model of hemoglobin desaturation solely derived from
      physiological considerations.

PMID- 9771573
TI  - Characterization of flow emerging from a stenosis using MRI.
AB  - MRI ultra-fast imaging techniques are used to characterize flow emerging from
      streamlined and abrupt stenoses inside cylindrical channels. Reattachment lengths
      of the shear boundary to the channel wall are measured using rotating ultra-fast
      imaging sequence (RUFIS) in-flow imaging. Velocity profiles of flow are created
      using velocity (sine and cosine)-encoded RUFIS sequences. The sine-encoded images
      permit one to identify reverse flow (i.e., eddies) that arise within the region
      of flow reattachment. The ratios of peak velocities (downstream/upstream of the
      stenosis) derived from the cosine-encoded images are used to identify the
      transition from the laminar to the turbulent regimen. Based on these experiments,
      the transition from the laminar to turbulent regimen occurs at a stenotic
      Reynolds Number of 350, whereas fully developed turbulence occurs at a stenotic
      Reynolds Number of 2600. These results are compared with the results from
      invasive studies.

PMID- 9771574
TI  - 3D time-resolved contrast-enhanced MR DSA: advantages and tradeoffs.
AB  - The 3D TRICKS method for contrast-enhanced, time-resolved MR DSA has been
      recently described. In this paper, computer simulations are used to investigate
      the relative frame rate, temporal window, artery-vein temporal separation,
      contrast-to-noise ratio, and spatial resolution of TRICKS and conventional scans
      for breath-hold and non-breath-hold applications. For non-breath-hold
      applications, TRICKS can be configured to provide increased CNR or spatial
      resolution at an increased frame rate, but with a longer temporal window when
      compared with a series of conventional scans in which the central portion of k
      space is sampled at the same rate as for the TRICKS scans. For breath-hold
      applications, TRICKS typically provides three images with 75% of the conventional
      single acquisition spatial resolution and is more tolerant of variations in
      contrast curve shape within the field of view.

PMID- 9771575
TI  - Artifacts induced by concomitant magnetic field in fast spin-echo imaging.
AB  - It has been observed that fast spin-echo (FSE) images with a large field of view
      (>40 cm) in certain directions exhibit unusual ghosting artifacts that cannot be
      eliminated with existing ghost removal methods. These artifacts have been related
      to a higher-order magnetic field perturbation (known as the concomitant field, or
      Maxwell field) concomitant to the linear imaging gradient, in accordance with the
      Maxwell equations V z B = 0 and V x B approximately 0. Several methods have been
      developed to eliminate or minimize the effects of the concomitant magnetic field
      by redesigning the FSE pulse sequences. In the slice-selection direction, the
      gradient waveforms are made symmetrical about the refocusing RF pulses wherever
      possible. Surrounding the first refocusing pulse, such symmetry cannot be
      achieved due to the slice-refocusing gradient, which is often combined with the
      left crusher. In this case, it is shown how crusher gradients can be reshaped to
      nullify the phase due to the concomitant field. In the phase-encoding direction,
      the gradient amplitude is reduced and its duration is prolonged. Artifacts due to
      the readout gradient are eliminated by reshaping the prephasing lobe, while
      keeping its area fixed. In all the three directions, the gradient waveforms are
      adjusted so that they have minimal overlap. Selected methods have been
      implemented on a clinical scanner, and typically reduce the ghost intensities in
      phantom and human images by a factor of 3.

PMID- 9771576
TI  - Accurate determination of spin-density and T1 in the presence of RF-field
      inhomogeneities and flip-angle miscalibration.
AB  - A method is presented for the accurate extraction of relative spin-density (rho0)
      and spin-lattice relaxation time (T1) in the presence of RF-field inhomogeneities
      and flip-angle miscalibration. The method requires collecting images at several
      flip-angles with a three-dimensional, spoiled steady-state, gradient-echo imaging
      sequence. Results show that the predominant effect of an overestimated flip-angle
      is to shift the T1 estimate to a higher value, whereas reductions in the
      normalized RF-field from unity cause rho0 and T1 distributions to be skewed
      toward lower values. Phantom and in vivo results demonstrate that the proposed
      method overcomes both of these systematic errors. The method was shown to be
      valid for up to a 50% reduction in RF sensitivity. A self-consistency argument
      was used to validate the absence of systematic errors in the extracted rho0 and
      T1 values over a large number of voxels. This made it possible to obtain a very
      precise estimate of muscle T1 at 1.5 T, yielding a 95% confidence interval of
      (1077.7 +/- 3.5) ms.

PMID- 9771577
TI  - One-shot spatially resolved velocity imaging.
AB  - For quantitative velocity measurement, we have developed a technique that
      acquires full velocity spectra without cardiac gating. After a cylindrical
      excitation restricts imaging to one spatial dimension, data are acquired while an
      oscillating gradient is played out. After each excitation, an image of velocity
      versus spatial location is obtained. For a given spatial location, a series of
      these images can be used to form an image of velocity versus time. Acquisition
      times are much shorter than for phase-contrast imaging or Fourier-encoded
      velocity imaging, obviating the need for cardiac gating. Although a two-shot
      version of this technique has been presented previously, we have developed a one
      shot version that offers higher temporal resolution for a given velocity
      resolution and superior off-resonance properties.

PMID- 9771578
TI  - Functional burst imaging.
AB  - A quiet magnetic resonance (MR) imaging technique for detecting changes in
      cerebral activity functions is presented. This single-shot method, functional
      Burst imaging (FBI), combines elements of Burst imaging with an offset technique
      known as asymmetric spin echo (ASE). The FBI sequence has the unique feature of
      being nearly silent, because of the low number of gradient switching steps
      involved. Furthermore, this approach has the key advantage that it can be
      implemented on conventional MR systems. Established auditory and visual paradigms
      were used to evaluate whether FBI can detect changes in cerebral activity using a
      1.5 Tesla MR system. In a second set of experiments, the FBI technique was used
      to evaluate cerebral activity changes during different sleep stages in humans.
      The results obtained demonstrate that the FBI sequence provides an alternative
      approach for functional imaging of brain activity in primary and secondary
      sensory areas of the human brain. Furthermore, in using this quiet MR technique,
      it was possible to scan continuously during different stages of human sleep
      without acoustic noise perturbation.

PMID- 9771579
TI  - Single-shot diffusion-weighted trace imaging on a clinical scanner.
AB  - The single-shot trace-weighted acquisition scheme for isotropic diffusion imaging
      suggested by Mori and van Zijl (Magn. Reson. Med. 33, 41-52 (1995)) was
      implemented on a clinical scanner in combination with echo-planar imaging. The
      results on phantoms and seven volunteers show that good-quality multiplanar
      isotropic diffusion-weighted images can be obtained within seconds and absolute
      Dav images within 10-40 s, depending on the number of gradient strengths used.
      However, care has to be taken in using this type of multi-bipolar-gradient
      sequence to avoid measurement of artifactual diffusion constants due to
      background gradient interference. It is outlined how to test for this
      interference and how to optimize for the correct experiment.

PMID- 9771580
TI  - Strategy for lipid suppression in lactate imaging using STIR-DQCT: a study of
      hypoxic-ischemic brain injury.
AB  - In vivo lactate detection using gradient enhanced double quantum coherence
      transfer (DQCT) was significantly improved by addition of short-time-inversion
      recovery (STIR). Phantom studies demonstrated lipid suppression down to the
      background noise level with 33% loss of lactate signal. In vivo studies using a
      rabbit model of hypoxic and unilateral-ischemic brain injury showed reduction
      down to 29 +/- 11% in lipids with inversion times between 140 and 170 ms. Lactate
      signals on the ischemic side were 51 +/- 53% higher than the nonischemic side at
      the peak of hypoxia. STIR-DQCT can be a useful robust method of obtaining
      metabolic maps of lactate in vivo.

PMID- 9771581
TI  - Evaluation of respiratory artifact correction techniques in multishot spiral
      functional MRI using receiver operator characteristic analyses.
AB  - Navigator corrections and low-spatial frequency (LSF) oversampling are
      investigated as methods for reducing respiration-related effects in multishot
      functional MRI. Both techniques take advantage of the smoothly varying or nearly
      constant phase variations linked to the respiration cycle. These techniques were
      tested in functional MRI studies with spiral k-space acquisitions. Receiver
      operator characteristic (ROC) analyses and the temporal variance averaged across
      the brain were used to evaluate their effectiveness. Both methods were found to
      increase the area under the ROC curve and to reduce the standard deviation, with
      the LSF oversampling method being more effective.

PMID- 9771582
TI  - A technique for determining the spatial relationship between the rotator cuff and
      the subacromial space in arm abduction using MRI and 3D image processing.
AB  - An MR imaging-based technique for three-dimensional determination of subacromial
      space width in relation to the rotator cuff in arm abduction is presented. Five
      volunteers were examined in an open MRI in seven arm positions, and coronal
      images were obtained with a gradient-echo sequence. 3D reconstruction of the
      bones and the supraspinatus was performed, and the minimal spatial distances
      between acromion, clavicle, and humerus were calculated. The closest contact
      between the supraspinatus and the anterior inferior part of the acromion occurred
      at 90 degrees abduction in internal rotation. The technique presented allows
      investigation of the morphological basis of the impingement syndrome.

PMID- 9771584
TI  - Microwave irradiation influences on the state of human cell nuclei.
AB  - Changes of electrokinetic properties of cell nuclei and the quantity of granules
      of heterochromatin located near the nuclear envelope in nuclei of human buccal
      epithelium cells were studied under the influence of electromagnetic fields in
      vitro. Irradiation of cells was realized by means of a semiconductor generator of
      millimeter radiation (wavelength 7.1 mm, frequency 42.2 GHz), the Yav-1 apparatus
      for extremely high frequency therapy. It was shown that irradiation of cells
      induced a decrease in electric charge of native human buccal epithelium cell
      nuclei and an increase in chromatin condensation in nuclei. The observed effects
      depend on irradiation dose and individual peculiarities of donors.

PMID- 9771583
TI  - Current state and implications of research on biological effects of millimeter
      waves: a review of the literature.
AB  - In recent years, research into biological and medical effects of millimeter waves
      (MMW) has expanded greatly. This paper analyzes general trends in the area and
      briefly reviews the most significant publications, proceeding from cell-free
      systems, dosimetry, and spectroscopy issues through cultured cells and isolated
      organs to animals and humans. The studies reviewed demonstrate effects of low
      intensity MMW (10 mW/cm2 and less) on cell growth and proliferation, activity of
      enzymes, state of cell genetic apparatus, function of excitable membranes,
      peripheral receptors, and other biological systems. In animals and humans, local
      MMW exposure stimulated tissue repair and regeneration, alleviated stress
      reactions, and facilitated recovery in a wide range of diseases (MMW therapy).
      Many reported MMW effects could not be readily explained by temperature changes
      during irradiation. The paper outlines some problems and uncertainties in the MMW
      research area, identifies tasks for future studies, and discusses possible
      implications for development of exposure safety criteria and guidelines.

PMID- 9771585
TI  - Heating of tissues by microwaves: a model analysis.
AB  - We consider the thermal response times for heating of tissue subject to
      nonionizing (microwave or infrared) radiation. The analysis is based on a
      dimensionless form of the bioheat equation. The thermal response is governed by
      two time constants: one (tau1) pertains to heat convection by blood flow, and is
      of the order of 20-30 min for physiologically normal perfusion rates; the second
      (tau2) characterizes heat conduction and varies as the square of a distance that
      characterizes the spatial extent of the heating. Two idealized cases are
      examined. The first is a tissue block with an insulated surface, subject to
      irradiation with an exponentially decreasing specific absorption rate, which
      models a large surface area of tissue exposed to microwaves. The second is a
      hemispherical region of tissue exposed at a spatially uniform specific absorption
      rate, which models localized exposure. In both cases, the steady-state
      temperature increase can be written as the product of the incident power density
      and an effective time constant tau(eff), which is defined for each geometry as an
      appropriate function of tau1 and tau2. In appropriate limits of the ratio of
      these time constants, the local temperature rise is dominated by conductive or
      convective heat transport. Predictions of the block model agree well with recent
      data for the thresholds for perception of warmth or pain from exposure to
      microwave energy. Using these concepts, we developed a thermal averaging time
      that might be used in standards for human exposure to microwave radiation, to
      limit the temperature rise in tissue from radiation by pulsed sources. We compare
      the ANSI exposure standards for microwaves and infrared laser radiation with
      respect to the maximal increase in tissue temperature that would be allowed at
      the maximal permissible exposures. A historical appendix presents the origin of
      the 6-min averaging time used in the microwave standard.

PMID- 9771586
TI  - Effect of sinusoidal 50 Hz magnetic field on the testosterone production of mouse
      primary Leydig cell culture.
AB  - This study evaluated the effect of sinusoidal 50 Hz magnetic field on the basal
      and human chorionic gonadotropin (hCG)-stimulated testosterone (T) production of
      48-h mouse Leydig cell culture. The luteinizing hormone (LH) analog hCG was used
      to check the T response of the controls and to evaluate the possible effect of
      the applied magnetic field on the steroidogenic capacity of the exposed cells.
      Leydig cells were obtained from the testes of 35- to 45-g CFLP mice and isolated
      by mechanical dissociation without enzyme treatment. The cell cultures were
      exposed to sinusoidal 50 Hz 100 microT (root mean square) AC magnetic field
      during the entire time of a 48-h incubation. Testosterone content of the culture
      media was measured by radioimmunoassay. In cultures exposed to the magnetic
      field, a marked increase of basal T production was found (P < .05), compared with
      the unexposed controls, whereas no significant difference was seen between the
      exposed or unexposed cultures in the presence of maximally stimulating
      concentration of hCG. These findings demonstrate that sinusoidal 50 Hz 100 microT
      magnetic fields are able to stimulate the basal T production of primary mouse
      Leydig cell culture, leaving the steroidogenic responsiveness to hCG unaltered.

PMID- 9771587
TI  - Intracerebroventricular injection of mu- and delta-opiate receptor antagonists
      block 60 Hz magnetic field-induced decreases in cholinergic activity in the
      frontal cortex and hippocampus of the rat.
AB  - In previous research, we have found that acute exposure to a 60 Hz magnetic field
      decreased cholinergic activity in the frontal cortex and hippocampus of the rat
      as measured by sodium-dependent high-affinity choline uptake activity. We
      concluded that the effect was mediated by endogenous opioids inside the brain
      because it could be blocked by pretreatment of rats before magnetic field
      exposure with the opiate antagonist naltrexone, but not by the peripheral
      antagonist naloxone methiodide. In the present study, the involvement of opiate
      receptor subtypes was investigated. Rats were pretreated by
      intracerebroventricular injection of the mu-opiate receptor antagonist, beta
      funaltrexamine, or the delta-opiate receptor antagonist, naltrindole, before
      exposure to a 60 Hz magnetic field (2 mT, 1 hour). It was found that the effects
      of magnetic field on high-affinity choline uptake in the frontal cortex and
      hippocampus were blocked by the drug treatments. These data indicate that both mu
      and delta-opiate receptors in the brain are involved in the magnetic field
      induced decreases in cholinergic activity in the frontal cortex and hippocampus
      of the rat.

PMID- 9771588
TI  - Progesterone concentrations during estrous cycle of dairy cows exposed to
      electric and magnetic fields.
AB  - Sixteen multiparous nonpregnant lactating Holstein cows (each weighing 662 +/- 65
      kg in 150.4 +/- 40 day of lactation) were confined to wooden metabolic cages with
      12:12 h light:dark cycle during the experiment. The cows were divided into two
      sequences of eight cows each and exposed to electric and magnetic fields (EMF) in
      an exposure chamber. This chamber produced a vertical electric field of 10 kV/m
      and a uniform horizontal magnetic field of 30 microT at 60 Hz. One sequence was
      exposed for three estrous cycles of 24 to 27 days. During the first estrous
      cycle, the electric and magnetic fields were off; during the second estrous
      cycle, they were on; and during the third estrous cycle, they were off. The
      second sequence was also exposed for three 24 to 26 days estrous cycles, but the
      exposure to the fields was reversed (first estrous cycle, on; second estrous
      cycle, off; third estrous cycle, on). The length of each exposure period (21 to
      27 days) varied according to the estrous cycle length. No differences were
      detected in plasma progesterone concentrations and area under the progesterone
      curve during estrous cycles between EMF nonexposed and exposed periods (2.28 +/-
      0.17 and 2.25 +/- 0.17; and 24.5 +/- 1.9 vs. 26.4 +/- 1.9 ng/ml, respectively).
      However, estrous cycle length, determined by the presence of a functional corpus
      luteum detected by concentrations of progesterone equal to or more than 1 ng/ml
      plasma, was shorter in nonexposed cows than when they were exposed to EMF (22.0
      +/- 0.9 vs. 25.3 +/- 1.4 days).

PMID- 9771589
TI  - Imaging basilar skull fractures in the horse: a review.
AB  - Due to the complex nature of the anatomy of the equine head, superimposition of
      numerous structures, and poor soft tissue differentiation, radiography may be of
      limited value in the diagnosis of basilar skull fractures. However, in many
      horses radiographic changes such as soft tissue opacification of the guttural
      pouch region, irregular bone margination at the sphenooccipital line, attenuation
      of the nasopharynx, ventral displacement of the dorsal pharyngeal wall and the
      presence of irregularly shaped bone fragments in the region of the guttural
      pouches are suggestive of a fracture of the skull base. These findings in
      conjunction with physical examination findings and historical information may
      lead to a presumptive diagnosis of a fracture. When available and when the
      patient will accommodate the equipment, computed tomography may give a definitive
      diagnosis owing to its superior resolution and differentiation of soft tissue
      structures.

PMID- 9771590
TI  - In vitro evaluation of contrast medium concentration and depth effects on the
      radiographic appearance of specific canine urolith mineral types.
AB  - Nine pure mineral types of canine uroliths (bladder or urethral origin only)
      identified in a chronologic sample from the Minnesota Urolith Center were
      compared to sequential dilutions of iodinated radiographic contrast medium in
      vitro. The uroliths studied were those composed of 100% magnesium ammonium
      phosphate, calcium oxalate monohydrate, calcium oxalate dihydrate, calcium
      phosphate appatite, calcium hydrogen phosphate dihydrate (brushite), ammonium
      acid urate, sodium acid urate, cystine, and silica. The radiopacity of the
      uroliths was classified as radiolucent, isopaque, or radiopaque, as compared to
      the radiopacity of the contrast medium solutions in which they were placed, using
      2.0 mm and 5.0 mm depths in petri dishes radiographed using a table-top
      technique. A statistically significant relationship was found between the
      effective atomic number of the uroliths and the effective atomic number of the
      contrast medium solutions to which they were compared for the endpoints of
      isopacity, first lucency (in increasing iodine concentration sequence), and
      optimal visualization of internal architecture. In general, uroliths isopaque or
      radiolucent in contrast medium solutions weaker than 23.5 mgI2/ml are most likely
      ammonium acid urate or sodium acid urate. Uroliths isopaque or radiolucent in
      contrast medium solutions between 23.5 mgI2/ml and 44.4 mgI2/ml are probably
      magnesium ammonium phosphate, cystine, or silica. Uroliths that remained
      radiopaque in solutions stronger than 44.4 mgI2/ml, and particularly those
      radiopaque in contrast medium solutions stronger than 80 mgI2/ml, almost always
      contained calcium. This relative opacity assessment is proposed for use in double
      contrast cystography as an aid in differentiating urolith mineral types
      clinically to facilitate appropriate use of medical protocols to dissolve
      uroliths or to prevent their growth or recurrence.

PMID- 9771591
TI  - The accuracy of the dorsoproximal-dorsodistal projection in assessing third
      carpal bone sclerosis in standardbred trotters.
AB  - Thirty-five carpal joints from 20 standardbred trotters, age 1 to 7 years, all
      euthanized for nonorthopedic reasons, were examined to investigate the
      correlation between assessments of subchondral bone sclerosis in the third carpal
      bone from radiographs in the dorsoproximal-dorsodistal (DPr-DDi) projection and
      histomorphometric bone volume density measurements. The agreement between
      assessments of sclerosis from antemortem versus postmortem radiographs was also
      evaluated. Bones graded as sclerotic in the DPr-DDi projection had significantly
      higher bone volume density values for all areas of measurement than nonsclerotic
      bones. For sclerotic bones, grading of sclerosis was significantly associated
      with volume density measurements in the central cancellous bone only. There was a
      good agreement (Kw = 0.71) between assessments of radiographic bone sclerosis
      from antemortem versus postmortem radiographs.

PMID- 9771592
TI  - Radiographic diagnosis--lung lobe torsion.

PMID- 9771593
TI  - Radiographic diagnosis-tracheal eosinophilic granuloma/polyp.

PMID- 9771594
TI  - Ureteral diverticula in two dogs.
AB  - We describe ureteral diverticula in two dogs and briefly review the related
      literature. The diagnosis of this condition is radiographic and based on the
      excretory urographic observation of multiple ureteral outpouchings.
      Pathologically, ureteral transitional cell hyperplasia and mucinous metaplasia
      result in submucosal proliferation of the urothelium and the formation of crypts
      and small cysts. Ureteral diverticulosis in humans is associated with an
      increased risk of urothelial malignancies, such as transitional cell carcinoma of
      the urinary bladder. Clinically, both dogs were older, small breed neutered
      females. Both had a history of chronic urinary obstruction. One dog died during
      surgery to remove an adrenal mass, and the other was euthanized at the owner's
      request because of an inoperable bladder neoplasm. Histopathologic diagnosis of
      ureteral lesions confirmed the radiographic diagnosis of ureteral diverticula in
      both dogs.

PMID- 9771595
TI  - Ultrasonography of laryngeal masses in six cats and one dog.
AB  - Ultrasonography of laryngeal abnormalities in small animals allows the
      identification of laryngeal masses because of the resulting distortion of normal
      structural/anatomical relationships. It also allows fine-needle aspirates to be
      taken with minimal risk of causing hemorrhage or edema affecting the already
      narrowed laryngeal lumen. Findings in six cats and one dog with laryngeal
      abnormalities are described.

PMID- 9771596
TI  - Echocardiographic appearance of flail aortic valve in a dog with infective
      endocarditis.
AB  - A 4-year-old female Boxer was suffering from aortic valve endocarditis with
      perforation of the right coronary cusp resulting in a flail aortic cusp and
      subsequent acute aortic insufficiency. This flail aortic cusp was observed on M
      mode and two-dimensional endocardiograms as a free linear echostructure in the
      left ventricular outflow tract. Although rarely observed, a free linear
      echostructure seems more specific of a flail aortic valve than a shaggy
      echostructure, which can represent a free moving vegetation and thus be
      confusing. Severe acute aortic insufficiency resulted in an uncommon abnormal
      mitral valve motion in the absence of early mitral diastolic opening. The absence
      of early mitral valve opening was thought to be a consequence of coupled aortic
      regurgitation, reduced left ventricular compliance, and presumably delayed mitral
      valve opening secondary to coronary artery occlusion. An exaggerated septal
      diastolic dip accounted for the decreased transmitral inflow. All the usual
      contractility parameters were within normal range; subsequently, mitral valve
      motion alterations seem to be more reliable indicators of left ventricular
      dysfunction during acute aortic insufficiency.

PMID- 9771598
TI  - Estimation of bladder volume using ultrasonographic determination of cross
      sectional areas and linear measurements.
AB  - The purpose of this study was to determine if ultrasonographic measurement of
      multiple cross-sectional areas combined with linear dimensions of the bladder
      could be used as a method of estimating bladder volume in the dog, and, if so, to
      compare the accuracy of this estimation with that described previously using
      linear measurements alone. Fifty-two live dogs undergoing investigation for
      urological disease and 37 fresh canine cadavers were used for bladder volume
      determination. Maximal length, depth, width, and area were measured from the
      maximal longitudinal and transverse sonograms in each living animal. In cadavers,
      the cross-sectional area of the longitudinal section of the bladder was measured
      at one centimeter intervals, and the measurements were summed. Based on
      sequential partial regression analysis, the cross-sectional area of the
      longitudinal section of the bladder and length were the best predictors of actual
      bladder volume in living animals. However, based on the cadaver experiment, the
      best predictor of actual bladder volume was summed parasagittal area alone, and,
      in cadavers, this was a much better predictor of actual bladder volume than the
      combination of the cross-sectional area of the longitudinal section of the
      bladder and length. The formula derived in living dogs using the cross-sectional
      area of the longitudinal section of the bladder and length gave a less accurate
      estimation of bladder volume than a previously published formula where only
      linear measurements were used.

PMID- 9771597
TI  - Ultrasonographic diagnosis of persistent hyperplastic tunica vasculosa
      lentis/persistent hyperplastic primary vitreous in two dogs.
AB  - Ultrasonography was performed on a Basset hound and a Doberman clinically
      suspected of persistent hyperplastic tunica vasculosa lentis/persistent
      hyperplastic primary vitreous. In both dogs, hyperechoic lenses with a triangular
      shaped echodense structure retrolentally were visible, and a very thin
      hyperechoic strand was seen penetrating the anechoic vitreous from this
      retrolental tissue to the area of the optic nerve. Using color Doppler imaging,
      blood flow was evident in parts of the retina in both dogs. With power Doppler
      imaging there was blood flow in the lens and hyperechoic strand of the Basset
      hound on the first examination; whereas, on re-examination 5 months later, this
      was not found. Other abnormalities, such as retinal detachment, endophthalmitis,
      vitreous hemorrhage, microphthalmia, and posterior neoplasia could be excluded.

PMID- 9771599
TI  - Evaluation of renal hemodynamics in awake and isoflurane-anesthetized cats with
      pulsed-wave Doppler and quantitative renal scintigraphy.
AB  - The feasibility and reproducibility of obtaining the pulsed-wave Doppler
      measurements of resistive index (RI) and pulsatility index (PI) were investigated
      in intrarenal arteries of normal, nonsedated cats, and cats anesthetized with
      isoflurane. In addition, relative renal function and relative renal blood flow
      were evaluated using quantitative renal scintigraphy. The percentage of injected
      dose uptake, time to peak activity, and two indices of renal blood flow (K/A
      ratio and flow index) obtained during the first pass of 99mTc-MAG3, were
      determined for both awake and anesthetized cats. Results indicate that measuring
      RI and PI in nonsedated cats is readily accomplished and that the results are
      reproducible within an animal. Mean RI and PI values in the awake cats were 0.55
      and 0.8, respectively. Significant differences between the awake and anesthetized
      cats were found for all pulsed-wave Doppler and quantitative renal scintigraphic
      measurements evaluated.

PMID- 9771600
TI  - Quantitative assessment of surgically induced mitral regurgitation using
      radionuclide ventriculography and first pass radionuclide angiography.
AB  - Radionuclide ventriculography has been used in humans to evaluate valvular
      incompetency. The stroke volume ratio, derived from the radionuclide
      ventriculogram, is used to quantify the severity of mitral regurgitation (MR).
      Previous studies conducted in humans have shown that left to right stroke volume
      ratio increases as the severity of MR increases. In this study, we evaluated
      radionuclide ventriculography as a noninvasive method to detect MR in dogs with
      surgically created mitral insufficiency. Six male and three female adult,
      conditioned mongrel dogs were used. Scintigraphic studies were performed prior to
      and 4 weeks after surgically created MR. Because of the overlap of the left and
      right ventricles when viewed from a left lateral position, we combined data from
      a first-pass radionuclide angiocardiogram with the radionuclide ventriculogram to
      obtain a corrected stroke volume ratio. Blood flow transit parameters were also
      derived from the first-pass radionuclide angiocardiogram. Standard left
      ventricular functional indices were also measured from the radionuclide
      ventriculogram. On the left lateral view of the heart, 25 to 30% of the right
      ventricular volume overlaps the left ventricle. After correcting for the overlap,
      the stroke volume ratio of normal dogs was 1.17+/-0.178 (mean+/-SD), which
      increased to 2.06+/-0.41 (mean+/-SD) (p < .001) 4 weeks after creation of MR. The
      was no significant change in left ventricular ejection fraction or peak rate of
      ejection following MR. The transit times of blood through the left ventricle were
      measured from the first-pass radionuclide angiocardiogram and were expressed as
      half-time clearance, peak clearance rate, and time to peak clearance rate. The
      baseline half-time clearance was 2.07+/-0.71 s (mean+/-SD), which increased to
      6.70+/-4.89 s (mean+/-SD) (p = .02) after creation of MR. The baseline peak
      clearance rate was 49.75+/-8.96 cts/s (mean+/-SD), which decreased to 23.12+/
      6.84 cts/s (mean+/-SD) (p < .001) after creation of MR. Stroke volume ratios
      significantly increased following creation of MR. Blood flow transit through the
      left ventricle slowed following creation of MR. The variability of these
      parameters were small in the baseline studies, suggesting these techniques may be
      clinically useful to gauge the severity of MR in dogs.

PMID- 9771601
TI  - Comparison between the scintigraphic uptake and plasma clearance of 99mTc
      diethylenetriaminepentacetic acid (DTPA) for the evaluation of the glomerular
      filtration rate in dogs.
AB  - The scintigraphically measured percentage dose uptake of 99mTc-DTPA by the
      kidneys and the plasma clearance of 99mTc-DTPA have been reported to correlate
      well with inulin clearance. These two parameters were evaluated in seven dogs
      with known or suspected naturally occurring renal disease and compared to
      simultaneously measured renal inulin clearance. Correlation between inulin
      clearance and the 99mTc-DTPA plasma clearance was better (p = .0016) than the
      correlation between the percentage DTPA uptake by the kidney. It was concluded
      that measurement of 99mTc-DTPA plasma clearance is a more accurate method to
      estimate global glomerular filtration rate (GFR) than the percentage kidney
      uptake.

PMID- 9771602
TI  - An accelerated technique for irradiation of malignant canine nasal and paranasal
      sinus tumors.
AB  - Tumor and normal tissue response was assessed in 21 dogs with malignant nasal
      tumors given 42 Gy cobalt radiation in 9 or 10 fractions over 11 to 13 days.
      Local tumor/clinical relapse recurred in 68% of dogs, with a median relapse free
      interval (RFI) of 270 days. Median survival was 428 days. One year survival for
      all dogs was 60%. RFI and survival times are better than, or similar to, previous
      reports of dogs treated with radiotherapy only. Acute radiation effects were
      severe in one dog. Late effects were severe in six of 15 dogs (40%) with durable
      tumor control. Late effects included bilateral blindness (3), osteoradionecrosis
      (3), and seizures (1). These six dogs had a median survival of 705 days. Loss of
      vision occurred in at least one eye in nine dogs (47%). Tumor staging based on CT
      findings was predictive for survival duration. Tumor histology was not predictive
      of outcome. Labrador Retrievers were significantly over-represented. Despite
      comparable or improved tumor control and survival times provided by this
      accelerated protocol, relative to other radiotherapy reports, local failure
      remains the major cause of death, and late radiation effects can be severe in
      dogs with durable tumor control.

PMID- 9771603
TI  - A survey of radiology reporting practices in veterinary teaching hospitals.
AB  - Radiologists from 28 veterinary schools and one private teaching hospital
      responded to a survey questionnaire focused on diagnostic image reporting.
      Radiologists at 26 hospitals generated a hard copy report on essentially all
      imaging studies performed. At 25 hospitals, radiologists dictated and
      transcriptionists typed all or most reports; radiologists at two institutions
      typed all or some of their reports. At five hospitals, preliminary and/or final
      handwritten reports were generated. The range of reports generated per day was
      <10 to 40 per radiologist on duty. Seven respondents generated reports as films
      came from the processor and another 12 routinely generated reports the day the
      studies were completed. Clinician access to a processed report averaged 2 to 4
      days after study was completed (reported range: several hours to 7 or more days).
      Fifteen responding radiologists personally mounted films from storage jackets for
      a majority of their reporting. Fourteen respondents generated reports from films
      mounted on motorized or stationary viewers. Nineteen respondents generated
      reports in a busy viewing area where they were frequently interrupted.
      Radiologists' impression of clinician and resident satisfaction regarding
      availability of radiology reports was that they were satisfied or very satisfied
      at 15 of the 29 hospitals. Five respondents reported that clinicians and
      residents were not concerned about availability of processed radiology reports.
      Thirteen radiologists were planning to change their reporting method within the
      next 2 years. The change most frequently sought (12 respondents) was to decrease
      turn-around time of reports. Ten radiologists indicated an interest in trying a
      voice recognition dictation system. The most common reasons given for not
      planning any changes in radiology reporting in the next 2 years were: limited
      number of radiologists (8) and "satisfied as is" (7). Turn-around of radiology
      reports at these veterinary institutions averaged 2 to 3 times longer than for
      radiology departments in human health-care facilities.

PMID- 9771604
TI  - Evaluation of bleeding sites with a tissue-specific sonographic contrast agent:
      preliminary experiences in an animal model.
AB  - The purpose of this study was to determine the feasibility and usefulness of
      using an ultrasonographic contrast agent to enhance the sonographic detection of
      bleeding sites in a canine model. SH U 563, an ultrasound contrast agent that
      elicits acoustic emission (i.e., random transient Doppler shifts produced by
      contrast particle rupture) even when stationary, was used. Acoustic emission is
      identified as a mosaic pattern on color Doppler imaging. A total of 13 active
      bleeding sites were created within intraabdominal organs (kidney and spleen, n =
      3), the urinary tract (n = 3), and the gastrointestinal tract (n = 7) in three
      canine models. Gray scale and color Doppler imaging studies were performed prior
      to and after each of 13 individual intravenous contrast agent administrations.
      Imaging results were compared to gross pathologic findings. After contrast agent
      administration, pooling of contrast medium-containing blood in the regions
      adjacent to bleeding sites could be detected with color Doppler imaging as
      regions with the characteristic acoustic emission color display. After injection
      gray scale imaging failed to demonstrate the location or extent of hemorrhaging
      adequately. A linear relationship existed between the blood loss due to
      gastrointestinal tract bleeding and the amount of acoustic emission detected (r2
      = 0.81). SH U 563 combined with color Doppler imaging improves the detection of
      bleeding sites in a variety of locations throughout the body.

PMID- 9771605
TI  - Three-dimensional power Doppler sonography of tumor vascularity.
AB  - The purpose of this study was to assess the value of routine clinical examination
      using three-dimensional power Doppler sonography of intratumoral blood flow.
      Twenty-two hepatocellular carcinomas, seven cases of hepatic metastasis, four
      hepatic hemangiomas, six renal cell carcinomas, two cases of hepatic focal
      nodular hyperplasia, and one case of splenic metastasis were included in the
      study. Three-dimensional images were reconstructed by maximum intensity
      projection method using cine-loop data on a built-in computer in a LOGIQ 500 and
      a LOGIQ 700 from GE Yokogawa Medical Systems. The three-dimensional images
      obtained were viewed multidirectionally on a monitor screen. Three-dimensional
      representations of intratumoral blood flow became available for all tumors
      approximately 5 s to 30 s after scanning. In every case, the entire vasculature
      of the tumor was appreciated more easily from three-dimensional images than from
      cross-sectional two-dimensional images. These three-dimensional images of
      intratumoral blood flows corresponded to the tumor vessels that could be
      visualized by angiography at the early arterial phase. Differential diagnosis of
      hepatic tumors based on distinct difference in their intratumoral vascular
      structures was performed. Our results suggest that three-dimensional power
      Doppler sonography can be used for routine clinical examination of tumor
      vascularity and may provide improved diagnostic information.

PMID- 9771607
TI  - Septate uterus: detection and prediction of obstetrical complications by
      different forms of ultrasonography.
AB  - The aims of the study were to compare the accuracy of transvaginal
      ultrasonography, transvaginal color Doppler sonography, hysterosonography, and
      three-dimensional ultrasonography in detection of septate uterus and to evaluate
      the occurrence of obstetrical complications in relation to septal dimension and
      vascularity. Each patient underwent transvaginal ultrasonography and color
      Doppler examination, whereas hysterosonography and three-dimensional
      ultrasonography were carried out in 76 and 86 patients, respectively. The
      sensitivity of different sonographic imaging modalities ranges between 95.21% and
      99.29%. Color and pulsed Doppler sonographic studies of the septal area revealed
      vascularity in 71.22%. Patients with vascularized septa had a higher prevalence
      of obstetrical complications than those with avascularized septa (P < 0.05).
      Three-dimensional ultrasonography and hysterosonography are highly accurate
      diagnostic tools for detection of uterine septa. We found no correlation between
      septal dimension and rate of obstetrical complications, although pregnancy loss
      was most likely to occur in patients with vascularized septa.

PMID- 9771606
TI  - Carotid steal: report of ten cases.
AB  - The blood flow may be diverted from the external to the internal carotid artery
      via the carotid bulb in the absence of flow in the common carotid artery. We
      aimed to investigate the prevalence, hemodynamics, and clinical features of this
      condition. Reviewing the records of color duplex ultrasonographic examinations,
      we found carotid steal in 12 carotid arteries of 10 patients. In three patients
      flow in the ipsilateral external carotid artery was bidirectional. The steal had
      been demonstrated angiographically in six patients. The cause of the phenomenon
      was atherosclerosis, Takayasu arteritis, or trauma. Awareness of this pathway of
      collateral circulation may contribute to diagnostic work-up and expand management
      alternatives.

PMID- 9771608
TI  - Receiver operating characteristic curves of transvaginal Doppler blood flow
      measurements in benign and malignant adnexal tumors.
AB  - The role of receiver operating characteristic curves of transvaginal Doppler
      velocimetry in predicting malignancy was evaluated in 80 patients with benign and
      40 patients with malignant adnexal tumors. The mean values of peak systolic
      velocity did not differ significantly. Malignant tumors had a significantly
      higher end diastolic velocity and mean flow velocity than benign tumors. Benign
      tumors had a significantly higher ratio of peak systolic to end diastolic
      velocity, pulsatility index, and resistive index than malignant tumors. The
      diagnostic accuracies in predicting malignancy were as follows: peak systolic
      velocity, 62%; end diastolic velocity, 79%; ratio of peak systolic to end
      diastolic velocity, 63%; mean flow velocity, 73%; pulsatility index, 91%;
      resistive index, RI 92%. Doppler velocimetry analysis allows us to predict the
      presence of malignancy with limited reliability.

PMID- 9771609
TI  - Cubital tunnel syndrome: diagnosis by high-resolution ultrasonography.
AB  - The purpose of this study was to evaluate the morphologic changes in the ulnar
      nerve in cubital tunnel syndrome with high-resolution ultrasonography. The mean
      values of the short axis (cm) x long axis (cm) at the arm, epicondyle, and
      forearm levels were 0.057 +/- 0.01, 0.068 +/- 0.019, and 0.062 +/- 0.01 in
      control group; 0.069 +/- 0.04, 0.139 +/- 0.06, and 0.066 +/- 0.023 in the
      symptomatic side in patients with cubital tunnel syndrome; and 0.063 +/- 0.029,
      0.068 +/- 0.029, and 0.057 +/- 0.012 in the normal side in patients with cubital
      tunnel syndrome. No significant difference was found in the area (short axis x
      long axis) of the ulnar nerve at the arm, epicondyle and forearm levels between
      the left and right ulnar nerve in the control group and between the control group
      and the normal side in symptomatic patients. However, the mean value of the area
      of the ulnar nerve at the epicondyle level in symptomatic patients was
      significantly larger than that of the control group and that of the contralateral
      side in patients, and the P value was less than 0.001. High resolution
      ultrasonography can detect morphologic changes in the ulnar nerve accurately, and
      it could therefore be useful as a screening and even follow-up modality in
      patients with cubital tunnel syndrome.

PMID- 9771610
TI  - Three-dimensional ultrasonography of the fetal distal lower extremity: normal and
      abnormal.
AB  - The objective of this study was to compare two-dimensional and three-dimensional
      ultrasonographic evaluation of fetal distal lower extremities. Data from two
      dimensional and three-dimensional ultrasonographic examinations from 40 distal
      lower extremities in 33 fetuses from a predominantly high-risk patient population
      were compared. Three-dimensional ultrasonography routinely provided three
      orthogonal planes (coronal, sagittal, and axial) for distal lower extremity
      evaluation. Specific features of distal lower extremity evaluation were not
      different using two-dimensional and three-dimensional ultrasonography. Rotation
      of the rendered volume provided assistance in assessing all but one of 40 distal
      lower extremities. Time from image acquisition to assessment for two views
      (coronal and sagittal) was longer with three-dimensional ultrasonography (8.2
      min) than with two-dimensional ultrasonography (3.2 min). Confidence in the
      diagnosis of abnormal distal lower extremities was slightly improved using three
      dimensional ultrasonography compared to two-dimensional ultrasonography.
      Pregnancy management was assisted in three of the four cases with isolated limb
      anomalies. In conclusion, three-dimensional ultrasonography improves the ability
      to evaluate the fetal distal lower extremity because of the multiplanar nature of
      volume assessment and the ability to rotate volume data sets. In addition, it
      provides assistance in counseling families, particularly for cases involving
      isolated limb anomalies.

PMID- 9771611
TI  - Myometrial thickness in pregnancy: longitudinal sonographic study.
AB  - The purpose of this study was to evaluate in vivo the changes in myometrial
      thickness throughout pregnancy. Myometrial thickness was measured in 25 singleton
      uncomplicated pregnancies. Ultrasonographic sagittal and transverse sections were
      used to measure uterine wall thickness from the low anterior wall (lower segment)
      and the anterior, posterior, right, and left walls of the upper segment and from
      the fundus. In each case four measurements were made in the second and third
      trimesters. Myometrial thickness of the upper uterine segment remains fairly
      constant in the first and second trimesters of pregnancy, whereas a significant
      linear trend was found between a decreasing thickness of the lower uterine
      segment and advancing gestational age. Myometrial thickness is significantly
      increased behind the placental insertion site as compared to other portions of
      the uterine wall. These data may serve as baseline reference values for further
      studies in the antepartum fetal surveillance of high-risk pregnancies.

PMID- 9771612
TI  - Fetal gallstones in a contracted gallbladder: potential to simulate hepatic or
      peritoneal calcification.

PMID- 9771613
TI  - Isolated internal iliac vein thrombosis.

PMID- 9771614
TI  - Structure-affinity relationships of Val-Val and Val-Val-Val stereoisomers with
      the apical oligopeptide transporter in human intestinal Caco-2 cells.
AB  - The objective of this study was to elucidate the structural features of the
      stereoisomers of Val-Val and Val-Val-Val that afford optimal binding affinity for
      the apical oligopeptide transporter in human intestinal Caco-2 cells. Three
      dimensional conformations of cephalexin and Val stereoisomers were optimized
      using Chem-X molecular modeling software. Molecular features associated with the
      optimized conformations of the Val stereoisomers were analyzed to identify
      potential relationships with their binding affinities for the apical oligopeptide
      transporter. For Val-Val stereoisomers, the distance between the N-terminal amino
      group and the C-terminal carboxyl group, d(N1-C7), was found to have a linear
      relationship with their binding affinities at the 95% confidence level. For Val
      Val-Val stereoisomers, three molecular features were found to have linear
      relationships with their binding affinities at the 95% confidence level. These
      features included: a) the distance between the N-terminal amino group and the C
      terminal carboxyl group, d(N1-C11); b) the distance between the N-terminal amino
      group and the second peptide bond, d(N1-N9); and c) the molecular dipole moment.
      Principal component analysis on all molecular features of Val-Val-Val
      stereoisomers identified three components that accounted for 90% of the variance.
      A linear model built with these three components by multiple linear regression
      adequately described the binding affinities (r2 = 0.90). Results from the current
      study suggest that the distance between the N-terminal amino group and the C
      terminal carboxyl group is important for interaction with the apical oligopeptide
      transporter in Caco-2 cells. In addition, the binding affinities of the Val-Val
      Val stereoisomers appear to be influenced by additional factors, including the
      position of the second peptide bond and the molecular dipole moment.

PMID- 9771615
TI  - Targeting of naproxen covalently linked to HSA to sinusoidal cell types of the
      liver.
AB  - The kinetic behaviour of a naproxen human serum albumin conjugate (Nap23-HSA) was
      investigated in rats and in isolated perfused rat livers (IPRL), as compared to
      its active metabolite naproxen-lysine (Nap-lysine) and free naproxen. Through
      covalently linking the anti-inflammatory drug naproxen to HSA, this drug can be
      selectively delivered to non parenchymal cells of the liver. Liver endothelial
      and Kupffer cells play an important role in the pathogenesis of inflammatory
      liver diseases. Targeting naproxen to these cells might increase its efficacy and
      reduce the side effects. The altered kinetic properties of Nap23-HSA, after i.v.
      injection of 22 mg x kg(-1), as compared to an equimolar amount of the uncoupled
      drug, were demonstrated in vivo by a decrease in the steady state volume of
      distribution (41 +/- 5 vs. 134 +/- 19 ml x kg(-1)), a decrease in its clearance
      (0.48 +/- 0.05 vs. 0.63 +/- 0.1 ml x min(-1) x kg(-1)), a shorter plasma half
      life (60 +/- 11 vs. 152 +/- 44 min) and a sustained biliary excretion. Liver
      targeting of Nap23-HSA was clearly demonstrated: drug content of the liver 180
      min after injection was about 30 times higher for Nap23-HSA as compared to
      naproxen itself. The IPRL experiments showed that the Vmax of hepatic removal of
      the conjugate was 40 microg x min(-1) x g liver(-1). With doses below receptor
      saturation a rapid removal of the conjugate (t1/2 = 6 min) from the perfusion
      medium was found. In conclusion, this study demonstrates the saturable uptake of
      Nap23-HSA and its lysosomal degradation in both in vivo and IPRL experiments.
      Covalently linked naproxen is released as Nap-lysine. This active metabolite
      accumulates in Kupffer and endothelial cells in which it reaches therapeutic
      concentrations. Release from these cells leads to rapid uptake by hepatocytes and
      carrier mediated excretion into bile. Levels of Nap-lysine in bile and plasma
      reflect the slowest step in its generation: the proteolytic release in
      endothelial and Kupffer cells.

PMID- 9771616
TI  - Interaction of salicylic acid with verrucae assessed by FT-Raman spectroscopy.
AB  - FT-Raman spectroscopy has been used to investigate treated verrucae (warts from
      the sole of the foot) with a local application of a salicylic acid paint.
      Differences in the molecular structure of the stratum corneum across the verruca
      sample were observed, and by comparison with normal and hyperkeratotic skin it
      was concluded that the tissue around the edges of the verrucae was typically
      hyperkeratotic skin. In the centre of the verruca, the molecular structure of the
      skin was altered showing evidence of the interaction with salicylic acid.
      Salicylic acid was not observed in its characteristic dimerised acid structure,
      but spectroscopic evidence suggested that fission of the intermolecular H-bonding
      essentially cleaved the dimer. Observed changes in the v(CCO) stretching mode of
      the carboxyl and hydroxyl groups indicate the inter H-bonds have broken. These
      spectral changes are believed to be more consistent with salicylic acid bonding
      within the human papillomavirus-containing verruca tissue rather than simple acid
      dissociation upon dissolution in water within the tissue. No evidence for the
      presence of the other paint components, lactic acid and flexible collodion, was
      found in the verrucae spectra. This Raman approach may help to elucidate the
      molecular basis for therapeutic agents interacting with diseased skin.

PMID- 9771617
TI  - Distribution of free and liposomal cefoxitin in plasma and peritoneal fluid in a
      porcine intra-abdominal sepsis model.
AB  - The plasma and peritoneal fluid pharmacokinetic parameters obtained after the
      intravenous administration of free and liposomal cefoxitin were studied in a
      porcine model of intraabdominal sepsis. No prior assumptions were made to predict
      the number of compartments pertaining to drug clearance from the administration
      of either cefoxitin formulation. The experimental data obtained were applied to
      fit mathematical models of multiexponential drug clearance and the
      pharmacokinetic data were found to best fit a two-compartment open model.
      Liposomal encapsulation significantly altered the plasma drug distribution
      pattern resulting in changes in the magnitude of a number of pharmacokinetic
      parameters examined. The mean post-distributive half-life of liposomal cefoxitin
      was substantially longer than that of free cefoxitin by at least 3 times. The
      peritoneal cavity appeared to provide a reservoir for the initial distributive
      phase of rapid drug clearance from the plasma compartment followed by a less
      rapid post-distributive phase. The cumulative drug level, as determined by the
      area under the concentration curve (AUC) as a function of time, in the plasma of
      animals treated with liposomal cefoxitin was about 3-4 fold as high as that of
      animals treated with free cefoxitin. The differences in pharmacokinetic
      parameters appeared to account for the improved therapeutic efficacy of liposomal
      cefoxitin in this animal model.

PMID- 9771618
TI  - Liposomal formulations for oral immunotherapy: in-vitro stability in synthetic
      intestinal media and in-vivo efficacy in the mouse.
AB  - The aim of this work was to develop a liposomal formulation which could act as a
      carrier for allergens during oral desensitization therapy. A model protein,
      ovalbumin, was associated with negatively charged, multilamellar vesicles of
      various compositions and their stability in the presence of synthetic intestinal
      media (bile salt, pancreatic enzymes and their combination) was investigated.
      Liposomes containing soya phosphatidylcholine as the main lipid, regardless of
      their cholesterol content (20-40%), were unable to protect ovalbumin against the
      combined action of pancreatic enzymes and bile salt. In contrast, liposomes
      prepared from distearoylphosphatidylcholine and cholesterol (6:3.5 molar ratio)
      were more stable: about 50% of the lipid remained as liposomes after a 4-h
      incubation at 37 degrees C and intact ovalbumin could be demonstrated therein by
      immunoblotting. The immunomodulating properties of liposomes were tested by
      following changes in serum IgE levels (by passive cutaneous anaphylaxis) in
      Balb/C mice sensitized to ovalbumin, after feeding various preparations. In this
      model, free ovalbumin was able to provoke a premature fall in IgE levels, and
      liposomes, whatever their composition, contributed no further effect.

PMID- 9771619
TI  - Microdialysis assessment of 5-fluorouracil release from thermosensitive
      magnetoliposomes induced by an electromagnetic field in tumor-bearing mice.
AB  - The current study was designed to evaluate the properties of thermosensitive
      magnetoliposomes (TMs), a new drug carrier proposed by the authors, in an
      electromagnetic field pertaining to their selective heating and drug release
      under an in vivo condition. TMs containing 5-fluorouracil (5-FU) were prepared by
      reverse-phase evaporation, injected into the tumor mass of B 16-BL6 melanoma in
      mice, and selectively heated by a 500-kHz electromagnetic field. The release
      profile of 5-FU from TMs was examined by using a microdialysis technique. The
      temperature of TMs in the tumor was effectively elevated to 42 degrees C and
      maintained at this temperature, overcoming the "cooling effect" of blood flow and
      surrounding tissues. The release kinetics of 5-FU from TMs was successfully
      analyzed by physiological modeling, which allows the prediction of intratumor
      drug concentrations during electromagnetic field exposure under various
      conditions. In conclusion, this study first demonstrated an in vivo evidence for
      the electromagnetic field-induced thermosensitive release of a drug from TMs in a
      tumor with the use of microdialysis.

PMID- 9771620
TI  - Apparent interaction of dimethyl sulfoxide with cisplatin released from polymer
      delivery devices injected subcutaneously in dogs.
AB  - Local tissue toxicity, systemic toxicity and platinum pharmacokinetics were
      evaluated in 6 normal healthy beagle dogs injected subcutaneously with two
      formulations of a polylactide biodegradable polymer (Atrigel) system containing
      cisplatin. Dogs were injected 4 times at 30 day intervals at platinum dosages of
      70, 105 and 157.5 mg/m2 (dose escalation). Once pharmacokinetics were
      established, 29 dogs with spontaneous stage IIb appendicular osteosarcoma were
      treated with 4 injections of the same polymer system containing cisplatin at 70
      mg/m2 (20 dogs) and 100 mg/m2 (9 dogs) to establish efficacy against
      micrometastatic disease. Local tissue toxicity was variable. Systemic toxicity,
      as judged by clinicopathologic evaluation was not noted at any dose level or
      injection number. Interim (6 month) survival analysis revealed a median disease
      free interval of 180 days. Consistent platinum release characteristics were
      found, however, the lack of toxicity and decreased disease-free-interval raised
      concerns over the biologic activity of the cisplatin. Prior to completion of the
      study, it was discovered that dimethyl sulfoxide, the solvent used in the co
      polymer system, may be responsible for biologic inactivation of cisplatin. This
      was subsequently demonstrated in tissue culture assays. The clinical trial was
      suspended and dogs were treated with traditional chemotherapy.

PMID- 9771621
TI  - Reliability of clinicians' judgments about prolonged-speech targets.
AB  - Treatments for stuttering based on variants of Goldiamond's prolonged-speech
      procedure involve teaching clients to speak with novel speech patterns. Those
      speech patterns consist of specific skills, described with such terms as soft
      contacts, gentle onsets, and continuous vocalization. It might be expected that
      effective client learning of such speech skills would be dependent on clinicians'
      ability to reliably identify any departures from the correct production of such
      speech targets. The present study investigated clinicians' reliability in
      detecting such errors during a prolonged-speech treatment program. Results showed
      questionable intraclinician agreement and poor interclinician agreement.
      Nonetheless, the prolonged-speech program in question is known to be effective in
      controlling stuttered speech. The clinical and theoretical implications of these
      findings are discussed.

PMID- 9771622
TI  - Speaking-rate-induced variability in F2 trajectories.
AB  - This study examined speaking-rate-induced spectral and temporal variability of F2
      formant trajectories for target words produced in a carrier phrase at speaking
      rates ranging from fast to slow. F2 onset frequency measured at the first glottal
      pulse following the stop consonant release in target words was used to quantify
      the extent to which adjacent consonantal and vocalic gestures overlapped; F2
      target frequency was operationally defined as the first occurrence of a frequency
      minimum or maximum following F2 onset frequency. Regression analyses indicated
      70% of functions relating F2 onset and vowel duration were statistically
      significant. The strength of the effect was variable, however, and the direction
      of significant functions often differed from that predicted by a simple model of
      overlapping, sliding gestures. Results of a partial correlation analysis
      examining interrelationships among F2 onset, F2 target frequency, and vowel
      duration across the speaking rate range indicated that covariation of F2 target
      with vowel duration may obscure the relationship between F2 onset and vowel
      duration across rate. The results further suggested that a sliding based model of
      acoustic variability associated with speaking rate change only partially accounts
      for the present data, and that such a view accounts for some speakers' data
      better than others.

PMID- 9771623
TI  - Parameterization of the voice source by combining spectral decay and amplitude
      features of the glottal flow.
AB  - A new method is presented for the parameterization of glottal volume velocity
      waveforms that have been estimated by inverse filtering acoustic speech pressure
      signals. The new technique, Parameter for Spectral and Amplitude Features of the
      Glottal Flow (PSA), combines two features of voice production, the AC value and
      the spectral decay of the glottal flow, both of which contribute to changes in
      vocal loudness. PSA yields a single parameter that characterizes the glottal flow
      in different loudness conditions. By analyzing voices of 8 speakers it was shown
      that the new parameter correlates strongly with the sound pressure level of
      speech.

PMID- 9771624
TI  - Intentional changes in sound pressure level and rate: their impact on measures of
      respiration, phonation, and articulation.
AB  - The purpose of the study was to compare the effects of changing sound pressure
      level (SPL) and rate on respiratory, phonatory, and articulatory behavior during
      sentence production. Ten subjects, 5 men and 5 women, repeated the sentence, "I
      sell a sapapple again," under 5 SPL and 5 rate conditions. From a multi-channel
      recording, measures were made of lung volume (LV), SPL, fundamental frequency
      (F0), semitone standard deviation (STSD), and upper and lower lip displacements
      and peak velocities. Loud speech led to increases in LV initiation, LV
      termination, F0, STSD, and articulatory displacements and peak velocities for
      both lips. Token-to-token variability in these articulatory measures generally
      decreased as SPL increased, whereas rate increases were associated with increased
      lip movement variability. LV excursion decreased as rate increased. F0 for the
      men and STSD for both genders increased with rate. Lower lip displacements became
      smaller for faster speech. The interspeaker differences in velocity change as a
      function of rate contrasted with the more consistent velocity performance across
      speakers for changes in SPL. Because SPL and rate change are targeted in therapy
      for dysarthria, the present data suggest directions for future research with
      disordered speakers.

PMID- 9771625
TI  - Phonological words and stuttering on function words.
AB  - Stuttering on function words was examined in 51 people who stutter. The people
      who stutter were subdivided into young (2 to 6 years), middle (6 to 9 years), and
      older (9 to 12 years) child groups; teenagers (13 to 18 years); and adults (20 to
      40 years). As reported by previous researchers, children up to about age 9
      stuttered more on function words (pronouns, articles, prepositions, conjunctions,
      auxiliary verbs), whereas older people tended to stutter more on content words
      (nouns, main verbs, adverbs, adjectives). Function words in early positions in
      utterances, again as reported elsewhere, were more likely to be stuttered than
      function words at later positions in an utterance. This was most apparent for the
      younger groups of speakers. For the remaining analyses, utterances were segmented
      into phonological words on the basis of Selkirk's work (1984). Stuttering rate
      was higher when function words occurred in early phonological word positions than
      other phonological word positions whether the phonological word appeared in
      initial position in an utterance or not. Stuttering rate was highly dependent on
      whether the function word occurred before or after the single content word
      allowed in Selkirk's (1984) phonological words. This applied, once again, whether
      the phonological word was utterance-initial or not. It is argued that stuttering
      of function words before their content word in phonological words in young
      speakers is used as a delaying tactic when the forthcoming content word is not
      prepared for articulation.

PMID- 9771626
TI  - Effect of tape recording on perturbation measures.
AB  - Tape recorders have been shown to affect measures of voice perturbation. Few
      studies, however, have been conducted to quantitatively justify the use or
      exclusion of certain types of recorders in voice perturbation studies. This study
      used sinusoidal and triangular waves and synthesized vowels to compare
      perturbation measures extracted from directly digitized signals with those
      recorded and played back through various tape recorders, including 3 models of
      digital audio tape recorders, 2 models of analog audio cassette tape recorders,
      and 2 models of video tape recorders. Signal contamination for frequency
      perturbation values was found to be consistently minimal with digital recorders
      (percent jitter = 0.01%-0.02%), mildly increased with video recorders (0.05%
      0.10%), moderately increased with a high-quality analog audio cassette tape
      recorder (0.15%), and most prominent with a low-quality analog audio cassette
      tape recorder (0.24%). Recorder effect on amplitude perturbation measures was
      lowest in digital recorders (percent shimmer = 0.09%-0.20%), mildly to moderately
      increased in video recorders and a high-quality analog audio cassette tape
      recorder (0.25%-0.45%), and most prominent in a low-quality analog audio cassette
      tape recorder (0.98%). The effect of cassette tape material, length of spooled
      tape, and duration of analysis were also tested and are discussed.

PMID- 9771627
TI  - A note on vowel centralization in stuttering and nonstuttering individuals.
AB  - Inferences were made regarding vocal tract vowel space during fluently produced
      utterances through examination of the first two formant frequencies. Fifteen
      adult males served as subjects, representing separate groups of untreated and
      treated individuals who stutter and nonstuttering controls. The steady-state
      portion of formant one (F1) and formant two (F2) was examined in the production
      of various CVC tokens containing the vowels /i/, /u/, and /a/. Vocal tract vowel
      space was estimated three ways. The first analysis scheme involved measurement of
      formant frequency spacing. The second measure involved calculating the area of
      the vowel space triangle. The third measure was based on calculating the average
      Euclidean distance from each subject's midpoint "centroid" vocal tract position
      to the corresponding /i/, /u/, and /a/ points on the vowel triangle. The formant
      frequency spacing measures proved to be most revealing of group differences, with
      the untreated stutterers showing significantly greater vowel centralization than
      the treated group and control group. Discussion focuses on the vocal tract
      articulation characterizing fluent speech productions and possible treatment
      implications for persons who stutter.

PMID- 9771628
TI  - Auditory temporal order perception in younger and older adults.
AB  - This investigation examined the abilities of younger and older listeners to
      discriminate and identify temporal order of sounds presented in tonal sequences.
      It was hypothesized that older listeners would exhibit greater difficulty than
      younger listeners on both temporal processing tasks, particularly for complex
      stimulus patterns. It was also anticipated that tone order discrimination would
      be easier than tone order identification for all listeners. Listeners were
      younger and older adults with either normal hearing or mild-to-moderate
      sensorineural hearing losses. Stimuli were temporally contiguous three-tone
      sequences within a 1/3 octave frequency range centered at 4000 Hz. For the
      discrimination task, listeners discerned differences between standard and
      comparison stimulus sequences that varied in tonal temporal order. For the
      identification task, listeners identified tone order of a single sequence using
      labels of relative pitch. Older listeners performed more poorly than younger
      listeners on the discrimination task for the more complex pitch patterns and on
      the identification task for faster stimulus presentation rates. The results also
      showed that order discrimination is easier than order identification for all
      listeners. The effects of hearing loss on the ordering tasks were minimal.

PMID- 9771629
TI  - Aging and high-frequency hearing sensitivity.
AB  - As part of a large population-based study of hearing and aging, ultra high
      frequency (9-20 kHz) threshold measures are reported for 3396 participants
      grouped by age (48-59 years, n = 1233; 60-69 years, n = 1031; 70-79 years, n =
      851; 80-92 years, n = 281). Ultra high-frequency (UHF) thresholds were higher for
      older age groups. The percentage of unmeasurable responses also was significantly
      higher for older age groups and for higher frequencies in the UHF range. The
      observed age effects remained significant after adjusting for gender. In general,
      UHF thresholds were significantly higher for men compared to those for women at
      lower UHF frequencies (9-14 kHz), but were not significantly different by gender
      for the highest UHF frequencies (16, 18, and 20 kHz). After accounting for
      hearing loss at traditional audiometric frequencies (250-8000 Hz), the age effect
      still remained; even for comparable degrees of sensorineural hearing loss,
      participants in older age groups evidenced higher UHF thresholds.

PMID- 9771630
TI  - Speech perception performance in experienced cochlear-implant patients receiving
      the SPEAK processing strategy in the Nucleus Spectra-22 cochlear implant.
AB  - Sixteen experienced cochlear implant patients with a wide range of speech
      perception abilities received the SPEAK processing strategy in the Nucleus
      Spectra-22 cochlear implant. Speech perception was assessed in quiet and in noise
      with SPEAK and with the patients' previous strategies (for most, Multipeak) at
      the study onset, as well as after using SPEAK for 6 months. Comparisons were made
      within and across the two test sessions to elucidate possible learning effects.
      Patients were also asked to rate the strategies on seven speech recognition and
      sound quality scales. After 6 months' experience with SPEAK, patients showed
      significantly improved mean performance on a range of speech recognition measures
      in quiet and noise. When mean subjective ratings were compared over time there
      were no significant differences noted between strategies. However, many
      individuals rated the SPEAK strategy better for two or more of the seven
      subjective measures. Ratings for "appreciation of music" and "quality of my own
      voice" in particular were generally higher for SPEAK. Improvements were realized
      by patients with a wide range of speech perception abilities, including those
      with little or no open-set speech recognition.

PMID- 9771631
TI  - Optimizing the reliability of speech recognition scores.
AB  - Speech recognition assessment involves a dilemma because clinicians want a test
      that is short and reliable, but statistical principles dictate that a short test
      is unreliable. Curves representing the variability of test scores based on the
      binomial model reveal that approximately 450 scorable items are needed in order
      to optimize the reliability of a speech recognition test. A testing approach was
      developed to achieve this sample size while retaining the principal features of
      the most commonly accepted speech recognition tests (i.e., monosyllabic words
      presented in an open-set format, verbal responses, and right/wrong scoring). It
      involves the use of an interactive computer program to present CNC words in 50
      three-word groups, which are scored phonemically, resulting in 450 scorable
      items. Normal performance is described as a function of both presentation level
      and signal-to-noise ratio. Comparisons of test and retest scores for 100
      individuals with normal hearing and 100 persons with sensorineural losses
      revealed that the approach achieves the degree of reliability predicted by the
      binomial model for both groups. Phoneme scores accounted for 99% of the variance
      of word scores for most of the performance range encountered in clinical
      practice, making it possible for test outcomes based on phonemic scoring to be
      expressed in terms of equivalent word recognition scores.

PMID- 9771632
TI  - Causative alternations of children with specific language impairment.
AB  - Alternating verbs to indicate or to relinquish cause requires an understanding of
      semantic and syntactic knowledge. This study evaluated the ability of children
      with specific language impairment (SLI) to produce the causative alternation in
      comparison to age peers and to language peers. The children with SLI were
      proficient in lexically alternating verbs, yet provided fewer passive and
      periphrastic constructions and more different verbs and adjectival responses.
      Overgeneralization error data suggest that the semantic systems of some children
      with SLI were similar to their age comparisons. Individual differences within the
      SLI group suggested that some children were adept at providing syntactic
      responses and overgeneralizations, whereas some of the SLI group provided less
      mature responses of no alternations and no responses. These findings demonstrate
      a syntactic deficit in the causative alternation for some children with SLI.

PMID- 9771633
TI  - Variable use of African American English across two language sampling context.
AB  - This investigation compares the impact of two language sampling elicitation
      contexts, free play and picture description, on variability in the use of African
      American English (AAE). Subjects were 65 normally-developing African American 4;4
      to 6;3-year-old boys and girls from lower socioeconomic status homes.
      Comparisons of AAE production in the first 50 C units revealed significant
      differences by context. Picture descriptions elicited more AAE usage overall, a
      larger set of AAE types, and took less time. Gender differences in the use of AAE
      tokens were also apparent, with the boys using significantly more tokens than
      girls in the free play context. The use of AAE types and tokens was comparable
      for boys and girls in the picture description context. The advantages of language
      sampling with pictures to determine dialect usage is discussed.

PMID- 9771634
TI  - Gestures and words in early development of children with Down syndrome.
AB  - This study investigated the development of language and communication in children
      with Down syndrome (DS). More specifically, the aim was to examine the relations
      among verbal comprehension, verbal production, and gesture production in the very
      early stages of development. Forty children (age range: 10-49 months) with DS and
      40 children with normal development (age range: 8-17 months) participated in this
      study. Children with DS came from two Italian health centers. The communicative
      and linguistic development of children with DS was measured by administering the
      Italian version of the MacArthur Communicative Development Inventory. The
      children with DS were severely delayed when compared with normally developing
      children in reaching the developmental stages. In such children a dissociation
      emerged between verbal comprehension and production, in favor of comprehension,
      whereas a synchronous development was found between vocal lexical comprehension
      and gestural production. The individual differences previously reported in these
      children are also evident in all domains examined. There were no significant
      differences between children with DS and typically developing controls matched
      for lexical comprehension on verbal production. However the two groups differed
      significantly in gestural development, suggesting a "gesture advantage" in
      children with DS compared with controls matched for word comprehension. Some
      possible reasons for this dissociative profile are discussed.

PMID- 9771635
TI  - Nonword repetition and child language impairment.
AB  - A brief, processing-dependent, nonword repetition task, designed to minimize
      biases associated with traditional language tests, was investigated. In Study 1,
      no overlap in nonword repetition performance was found between a group of 20
      school-age children enrolled in language intervention (LI) and a group of 20 age
      matched peers developing language normally (LN). In Study 2, a comparison of
      likelihood ratios for the nonword repetition task and for a traditional language
      test revealed that nonword repetition distinguished between children
      independently identified as LI and LN with a high degree of accuracy, by contrast
      with the traditional language test. Nonword repetition may have considerable
      clinical utility as a screening measure for language impairment in children.
      Information on the likelihood ratios associated with all diagnostic tests of
      language is badly needed.

PMID- 9771636
TI  - Sensitivity to grammatical morphemes in children with specific language
      impairment.
AB  - Grammatical morphemes, such as articles and auxiliary verbs, provide potentially
      useful information to language learners. However, children with specific language
      impairment (SLI) frequently fail to produce grammatical morphemes, raising
      questions about their sensitivity to them. To address this issue, two experiments
      were conducted in which 3- to 5-year-old children with SLI and with normally
      developing language (NL) heard sentences asking them to identify a picture
      corresponding to a named target word. The target occurred in either a grammatical
      sentence or one with an incorrectly used grammatical morpheme. In Experiment 1,
      the picture representing the target occurred with three unrelated distractor
      pictures. In Experiment 2, distractor sets included pictures that were
      semantically related to the target. In both studies, the SLI group chose fewer
      correct pictures when the target followed an incorrectly used morpheme. In
      Experiment 2, the SLI group chose more semantically related than unrelated
      distractors. These results suggest that children with SLI are sensitive to
      grammatical morphemes and that their incorrect picture choices may reflect a
      failure to maintain the target in memory.

PMID- 9771637
TI  - Prosodic markers of syntactic boundaries in the speech of 4-year-old children
      with normal and disordered language development.
AB  - This study focuses on the potential role of prosodic "boundary features" in
      developmental disorders of morphosyntax. As exemplified melodically by the final
      portion of the falling tone and rhythmically by final syllable lengthening,
      boundary features mark the right edge of major constituent units in speech and
      thus phonetically reflect syntactic structure on the level of clauses and
      sentences. To resolve conflicting findings about the development of boundary
      features in children with specific language impairment (SLI), this study
      describes the falling tone and final syllable lengthening in the spontaneous
      speech of 10 four-year-old children with the phonologic-syntactic type of SLI and
      10 four-year-old children with normal language development. The results-
      indicating that some prosodic boundary features are normal in preschoolers with
      SLI--show that impairments of morphology and syntax on the segmental level of the
      grammar do not implicate systematic deficits in syntax-sensitive features on the
      suprasegmental level. The potential dissociation between prosodic and
      morphosyntactic development is shown most clearly by the remarkable robustness of
      the falling tone, which was observed in 9 of the 10 children with SLI, in spite
      of the moderate to severe deficits they demonstrated in segmental phonology,
      morphosyntax, and mean length of utterance.

PMID- 9771638
TI  - A prominence account of syllable reduction in early speech development: the
      child's prosodic phonology of tiger and giraffe.
AB  - When young children produce multiword utterances and words that are polysyllabic
      in adult speech, they are most likely to omit unstressed syllables. Because
      unstressed syllables are omitted more often in weak-strong (iambic) than in
      strong-weak (trochaic) environments, a trochaic metrical theory has been proposed
      to account for the asymmetrical omission pattern. This paper presents an
      alternative explanation based on the notion of relative prosodic prominence. I
      propose that syllable prominence is a product of two orthogonal suprasegmental
      systems: one that marks stress/accent peaks and one that marks phrase boundaries.
      A two-component scale of prominence values reflecting the contributions of both
      systems was used to analyze single- and multi-word speech samples of 11 children
      19 to 26 months of age. The results show that the prominence scale parsimoniously
      accounts not only for the bias toward syllable omissions in nontrochaic
      environments but also explains other types of syllable reduction not captured by
      metrical theories. Implications of the dual-system prosodic model are discussed
      in terms of possible contributions to a perceptually based theory of early
      polysyllabic and multiword patterns in child speech.

PMID- 9771639
TI  - Specific language impairment and grammatical morphology: a discriminant function
      analysis.
AB  - Discriminant function analysis was employed to determine if grammatical morpheme
      production could be used to classify preschool-age children with specific
      language impairment (SLI) and children with typically developing language skills.
      Three variables were included in the discriminant analysis: a finite verb
      morpheme composite, a noun morpheme composite, and mean length of utterance in
      morphemes. The children with SLI and age-matched controls were discriminated with
      high levels of accuracy, though the three variables did not yield identical
      classifications. Across two samples of typically developing children and children
      with SLI, the verb morpheme composite showed sensitivity exceeding 85% and
      specificity of 100%. In light of these results and growing evidence that problems
      with finite verb morphology continue into the school years in children with SLI,
      the verb morpheme composite was considered to hold promise as a clinical marker
      for SLI.

PMID- 9771640
TI  - Participation in cooperative learning activities by children with specific
      language impairment.
AB  - This study examined the involvement of children with specific language impairment
      (SLI) in a cooperative group task. Subjects consisted of 6 target children with
      SLI (ages 8;10 to 12;5), 6 target children matched for chronological age (CA),
      and 6 target children with similar language skills (LS). Each target subject
      interacted with 2 peers of the same age and gender. This resulted in 54 subjects
      participating in 18 triadic interactions (each involving 1 target subject and 2
      partners). Each triad of children worked together to build a cardboard periscope.
      Verbal and nonverbal collaborative activity were analyzed during the
      interactions. All members of the CA and LS triads were highly collaborative and
      worked and talked together while assembling the periscope. Four of the children
      with SLI played very minor roles in the cooperative work within their triads.
      Their verbal contributions were limited, and their nonverbal activity was
      minimal. When children with SLI did collaborate in building the periscope, they
      performed less specialized tasks than did their partners.

PMID- 9771641
TI  - Maternal responsivity predicts the prelinguistic communication intervention that
      facilitates generalized intentional communication.
AB  - Family systems theory posits that the relative effectiveness of early
      interventions will vary depending on various aspects of the family. This study
      tested whether maternal responsivity would predict the extent to which
      Prelinguistic Milieu Teaching (PMT) facilitated generalized intentional
      communication better than a contrast treatment that was conducted in a small
      group by a responsive adult (i.e., Responsive Small Group, RSG). Fifty-eight
      children with developmental disabilities in the prelinguistic communication
      period of development were randomly assigned to one of the two staff-implemented
      treatment groups. Thirty were assigned to RSG; 28 were assigned to PMT. Mothers
      were kept naive to the intervention methods, hypotheses, and measures. In
      families with mothers who responded to a high percentage of the children's
      communication acts at the pre-treatment period, the children in the PMT group
      used more frequent intentional communication in post-treatment generalization
      sessions with a trainer and mothers than did children in the RSG group. In the
      families with mothers who responded to fewer than 39% of their children's
      communication acts, children in the RSG intervention used more frequent
      intentional communication in post-treatment generalization sessions with the
      mothers than did children in the PMT intervention. Other family variables and no
      child variables that we measured could account for these findings.

PMID- 9771642
TI  - Cloning of the porcine interferon-gamma receptor and its foeto-endometrial
      expression in early pregnancy.
AB  - In early gestation, trophoblastic cells of porcine preimplanting conceptuses
      transiently and massively secrete two distinct interferons (IFNs), one of which
      is IFN-gamma. In order to localize possible cellular target(s) for this IFN
      gamma, the expression of the porcine IFN-gamma receptor and its developmental
      regulation have been investigated on the maternal endometrium and on the
      embryonic tissues. A cDNA encoding the porcine IFN-gamma binding-chain (pIFNGR1)
      was isolated. When expressed in COS-7 cells, it displayed a specific binding to
      radiolabelled pIFN-gamma and was shown to be a glycosylated membrane protein with
      an apparent molecular mass of 92 kDa. Porcine IFNGR1 mRNA was detected by RT-PCR
      not only in uterine epithelial cells but also in embryonic tissues from at least
      as early as day 10 of gestation. Moreover, membrane expression of the pIFN-gamma
      receptor quantified by binding and crosslinking of 32P-pIFN-gamma was
      demonstrated in uterine epithelium and in the trophoblast. In the trophoblast,
      expression of the receptor was found to be developmentally regulated: although
      expression was weak on days 12 and 15 of gestation, it reached a level similar to
      that found on some IFN-gamma-sensitive cells on day 16. This study shows that
      maternal endometrium is not the only possible target for trophoblastic IFN-gamma:
      the induction of pIFN-gamma receptor expression in the trophoblast around day 16
      of gestation could suggest the appearance of responsiveness to pIFN-gamma in this
      implanted tissue and therefore a possible delayed autocrine effect of
      trophoblastic pIFN-gamma.

PMID- 9771643
TI  - Two testicular cDNA clones suppressed by gonadotropin stimulation exhibit ZP2-
      and ZP3-like structures in Japanese eel.
AB  - A single injection of human chorionic gonadotropin (HCG) can induce complete
      spermatogenesis in immature eel testes consisting of premitotic spermatogonia. To
      understand the regulatory mechanisms of spermatogenesis, we have applied a
      subtractive hybridization method to identify genes in which changes in expression
      occur after HCG treatment in vivo. The subtraction was carried out 24 hours after
      HCG injection. Two up-regulated and six down-regulated cDNA clones by HCG
      stimulation were isolated, and named eel spermatogenesis-related substance (eSRS)
      1 to 8. In this paper, down-regulated cDNA clones of eSRS3 and eSRS4 were
      sequenced. A homology search showed that eSRS3 and eSRS4 have amino acid
      sequences similar to those of the ZP-domains of zona pellucida sperm-binding
      protein (ZP)-2 and 3, respectively. Transcripts of eSRS3 and eSRS4 have been
      detected only in immature testes and ovaries. Both transcripts disappeared
      immediately after HCG injection and were not detected in testes throughout the
      experimental period. To determine whether HCG action on down-regulation of eSRS3
      and eSRS4 transcription is direct or mediated through 11-ketotestosterone (11
      KT), a spermatogenesis-inducing steroid in eel, we investigated the effect of HCG
      and 11-KT on testicular eSRS3 and eSRS4 mRNA transcription in vitro. Northern
      blot analysis using poly(A)+ RNA extracted from cultured testis showed that both
      HCG and 11-KT suppressed the mRNA transcription of both eSRS3 and eSRS4. We
      speculate that eSRS3 and eSRS4 may play important roles in the prevention of
      spermatogenesis in the eel.

PMID- 9771644
TI  - Expression and regulation of genes associated with cell death during murine
      preimplantation embryo development.
AB  - The newly fertilized preimplantation embryo depends entirely on maternal mRNAs
      and proteins deposited and stored in the oocyte prior to its ovulation. If the
      oocyte is not sufficiently equipped with maternally stored products, or if
      zygotic gene expression does not commence at the correct time, the embryo will
      die. One of the major abnormalities observed during early development is cellular
      fragmentation. We showed previously that cellular fragmentation in human embryos
      can be attributed to programmed cell death (PCD). Here, we demonstrate that the
      PCD that occurs during the 1-cell stage of mouse embryogenesis is likely to be
      regulated by many cell death genes either maternally inherited or transcribed
      from the embryonic genome. We have demonstrated for the first time the temporal
      expression patterns of nine cell death regulatory genes, and our preliminary
      experiments show that the expression of these genes is altered in embryos
      undergoing fragmentation. The expression of genes involved in cell death (MA-3,
      p53, Bad, and Bcl-xS) seems to be elevated, whereas the expression of genes
      involved in cell survival (Bcl-2) is reduced. We propose that PCD may occur by
      default in embryos that fail to execute essential developmental events during the
      first cell cycle.

PMID- 9771645
TI  - Expression of fibroblast growth factor receptors in peri-implantation mouse
      embryos.
AB  - FGF receptor (FGFR) function is essential during peri-implantation mouse
      development. To understand which receptors are functioning, we tested for the
      expression of all four FGF receptors in peri-implantation blastocysts. By RT-PCR,
      FGFR-3 and FGFR-4 were detected at high levels, FGFR-2 at lower levels, and FGFR
      1 was detected at background levels compared to control tissues. Because FGFR-3
      and FGFR-4 were detected at the highest levels, we studied these in detail.
      Between 3.5 days after fertilization (E3.5) and E6.0, FGFR-4 mRNA was detected
      ubiquitously in the peri-implantation embryo, restricted to the inner cell mass
      (ICM) and its derivatives and primitive endoderm by E6.0, and was not detected at
      E6.5. FGFR-3 mRNA was detected ubiquitously in the peri-implantation embryo with
      a tendency towards extraembryonic cells. We tested blastocyst outgrowths, a model
      for implantation, for FGFR-3 and FGFR-4 protein. FGFR-3 protein was detected in
      all cells early during the outgrowth. Later, FGFR-3 was detected in the
      extraembryonic endoderm and trophoblast giant cells (TGC), but not in the ICM.
      FGFR-4 protein was detected in all cells of the implanting embryo, but was
      restricted to the ICM/primitive endoderm in later stage outgrowths. The
      distribution of the receptor proteins in the blastocyst outgrowths is similar to
      the distribution of the mRNA detected by in situ hybridization of sections of
      embryos. The data suggest roles for FGFR-3 and FGFR-4 in peri-implantation
      development.

PMID- 9771646
TI  - cDNA sequence and deduced amino acid sequence of bovine oviductal fluid catalase.
AB  - A bovine oviductal fluid catalase (OFC) which preferentially binds to the
      acrosome surface of some mammalian spermatozoa has recently been purified. The
      objectives of this study were to clone the OFC, obtain the full-length cDNA and
      protein sequence and determine which characteristics of the proteins are
      associated with the binding of the enzyme to sperm surface. Northern blot
      analysis revealed low levels of catalase mRNA in bovine oviducts and uterus
      compared to the liver and kidney. Screening of a cDNA library from the cow
      oviduct permit to obtain a full-length cDNA of 2282 bp, with an open reading
      frame of 1581 bp coding for a deduced protein of 526 amino acids (59,789 Da). The
      deduced protein contained four potential N-glycosylation sites and many potential
      O-glycosylation sites. The OFC protein exhibited high identity with catalase from
      other bovine tissues, likewise with catalases from human fibroblast and kidney,
      and with rat liver catalase. The homology of amino acid sequence of OFC with
      bovine liver catalase was about 99%. However the OFC possess an extended carboxyl
      terminus of 20 amino acids not present on the liver catalase. This result is
      supported by a lower mobility of the OFC compared to the liver catalase when both
      proteins are submitted on SDS-PAGE.

PMID- 9771647
TI  - Cre expression in primary spermatocytes: a tool for genetic engineering of the
      germ line.
AB  - Transgenic mice were generated expressing a testicular Cre recombinase driven by
      promoter sequences derived from the gene encoding Synaptonemal Complex Protein 1
      (Sycp1), expressed at an early stage of the male meiosis (leptotene to zygotene).
      Recombination at target LoxP sites was examined during germinal differentiation
      in mice harboring Sycp1-Cre and a second transgene where LoxP sites flank either
      the beta geo coding region, the Pgk1 promoter, or a tk-neo cassette inserted into
      the Rxr alpha locus. The LoxP-flanked transgenes were stably maintained in the
      somatic tissues of the double transgenic animals, as well as in the progeny of
      the females. Mice born after mating the double-transgenic males with normal
      females showed extensive deletions of the LoxP-flanked sequences. When the males
      were hemizygous for the Sycp1-Cre transgene, the deletions were observed even in
      the fraction of the offspring which had not inherited the Cre gene, thus
      demonstrating that expression occurred in the male parent during spermatogenesis.
      The high efficiency of excision at the LoxP sites makes the Sycp1-Cre transgenic
      males suitable for evaluating the role of defined gene functions in the germinal
      differentiation process.

PMID- 9771648
TI  - In vitro and in vivo survival of frozen-thawed bovine oocytes after IVF, nuclear
      transfer, and parthenogenetic activation.
AB  - Cryopreservation of bovine oocytes would be beneficial both for nuclear transfer
      and for preservation efforts. The overall objective of this study was to evaluate
      the viability as well as the cryodamage to the nucleus vs. cytoplasm of bovine
      oocytes following freezing-thawing of oocytes at immature (GV) and matured (MII)
      stages using in vitro fertilization (IVF), parthenogenetic activation, or nuclear
      transfer assays. Oocytes were collected from slaughterhouse ovaries. Oocytes at
      the GV, MII, or MII but enucleated (MIIe) stages were cryopreserved in 5% (v/v)
      ethylene glycol; 6% (v/v) 1,2-propanediol; and 0.1-M sucrose in PBS supplemented
      with 20% (v/v) fetal bovine serum. Frozen-thawed oocytes were subjected to IVF,
      parthenogenetic activation, or nuclear transfer assays. Significantly fewer GV
      oocytes survived (i.e., remained morphologically intact during freezing-thawing)
      than did MII oocytes (47% vs. 84%). Subsequent development of the surviving
      frozen-thawed GV and MII oocytes was not different (58% and 60% cleavage
      development; 7% and 12% blastocyst development at Day 9, respectively, P > 0.05).
      Parthenogenetic activation of frozen-thawed oocytes resulted in significantly
      lower rates of blastocyst development for the GV than the MII oocyte groups (1%
      vs. 14%). Nuclear transfer with cytoplasts derived from frozen-thawed GV, MII,
      MIIe, and fresh-MII control oocytes resulted in 5%, 16%, 14%, and 17% blastocyst
      development, respectively. However, results of preliminary embryo transfer trials
      showed that fewer pregnancies were produced from cloned embryos derived from
      frozen oocytes or cytoplasts (9%, n = 11 embryos) than from fresh ones (19%, n =
      21 embryos). Transfer of embryos derived by IVF from cryopreserved GV and MII
      oocytes also resulted in term development of calves. Our results showed that both
      GV and MII oocytes could survive freezing and were capable of developing into
      offspring following IVF or nuclear transfer. However, blastocyst development of
      frozen-thawed oocytes remains poorer than that of fresh oocytes, and our nuclear
      transfer assay suggests that this poorer development was likely caused by
      cryodamage to the oocyte cytoplasm as well as to the nucleus.

PMID- 9771649
TI  - Regulation of follicular luteinization by a gonadotropin-releasing hormone
      agonist: relationship between steroidogenesis and apoptosis.
AB  - The purpose of this study was to evaluate the effects of GnRH-analog (Leuprolide
      acetate, LA) administration on follicular luteinization in equine chorionic
      gonadotropin plus human chorionic gonadotropin (eCG + hCG)-superovulated
      prepubertal treated rats. Results indicate that LA treatment decreases
      circulating levels of progesterone (P) and P accumulation in collagenase
      dispersed ovarian cell cultures, though estradiol (E2) production is increased.
      These data suggest that cells from the LA group may be less luteinized following
      gonadotropin treatment. Studies performed on histological ovarian sections after
      different times of eCG administration showed that LA injections produce lower
      amounts of corpora lutea and antral follicles, and a greater number of atretic
      and preantral follicles. The basal and LH-stimulated P and progestagen
      accumulations are decreased in incubations of corpora lutea isolated from the LA
      group. In addition, the mitochondrial cholesterol side-chain cleavage (P450SCC)
      levels in corpora lutea from LA-treated rats are reduced, indicating that the
      decrease in P production observed is due in part to an alteration in the
      steroidogenic luteal capability. Immunocytochemical localization of nuclei
      exhibiting DNA fragmentation by the technique of terminal deoxynucleotidyl
      transferase end-labeling showed that LA treatment causes an increase in the
      number of apoptotic cells in preantral and antral follicles at all times studied
      (1, 2, 4, or 7 days of LA administration). A similar effect, though less
      pronounced, was observed in corpora lutea. It is concluded that LA treatment
      produces a failure in the steroidogenic luteal capability and an increase of
      apoptotic mechanisms in the ovary, producing as a consequence an interference in
      the follicular recruitment, growth, and luteinization induced by gonadotropins.

PMID- 9771650
TI  - Mechanisms leading to cortical reaction in the mammalian egg.
AB  - Activation of the mammalian egg results in cortical reaction (CR), which is
      correlated with an increase in intracellular Ca2+ concentration and PKC
      activation. The CR is a gradual rather then an "all or none" response, and can be
      regulated by different concentrations of parthenogenetic activators. To evaluate
      the biological significance of parthenogenetic induced CR, rat eggs were
      fertilized or activated by different concentrations of ionomycin and TPA.
      Cortical granules (CG) were monitored by electron microscopy, while the CG
      exudate was visualized by Lens culinaris lectin and Texas Red, using light and
      confocal microscopy. The ability of the CR to trigger a full block to polyspermy
      was examined in an IVF system. Our study demonstrates the existence of light and
      dark CG, which differ by number, distribution in the egg cortex, and sensitivity
      to parthenogenetic activators. Sperm penetration or high concentration of
      activators, trigger depletion of both light and dark CG, leading to a full CR.
      Low concentration of activators altered the CG density, the ratio of dark/light
      CG, and induced partial CR that was sufficient to cause a block to polyspermy.
      The results imply that Ca2+ rise or PKC activation have different effects on
      light and dark CG. In recently fertilized or parthenogenetically activated eggs,
      CG exudate appeared as evenly distributed spots, whereas in more advanced stages
      of fertilization the exudate was scattered as patchy aggregates. This observation
      suggests a difference in the dispersion of CG exudate after fertilization as
      compared to parthenogenetic activation.

PMID- 9771651
TI  - Regulation of protein tyrosine phosphorylation in boar sperm through a cAMP
      dependent pathway.
AB  - Changes of protein tyrosine phosphorylation in ejaculated boar sperm incubated in
      vitro were examined with the use of antiphosphotyrosine antibodies and
      immunoblotting. The intracellular levels of cAMP were modulated by treatment with
      various combinations of caffeine, 3-isobutyl-1-methylxanthine (IBMX), and
      dibutyryl cyclic AMP (dbcAMP), and acrosome reactions (ARs) were induced via
      treatment with divalent cation ionophore A23187. Proteins of Mr 34, 38, 40, and
      44 (p34 ... p44) were strongly phosphorylated on tyrosine residues in freshly
      prepared sperm samples and at the same level during all subsequent treatments.
      Incubation of sperm in vitro for various periods of time induced an increase of
      tyrosine phosphorylation of p20, p93, and p175. The tyrosine phosphorylation of
      p93, p175, and several other sperm proteins was up-regulated in a concentration
      dependent manner following treatment of the sperm with dbcAMP, caffeine, or IBMX
      alone, or with combinations of caffeine and IBMX, respectively, with dbcAMP; the
      tyrosine phosphorylation of p20 was not correlated with treatment of sperm with
      cAMP-elevating reagents. The percentage of sperm cells undergoing spontaneous ARs
      was not affected by the manipulation of cAMP levels and was not correlated with
      protein tyrosine phosphorylation. In contrast, the addition of calcium to the
      incubation media decreased protein tyrosine phosphorylation and elevated
      percentage of spontaneous ARs. The induction of ARs with A23187 caused a
      significant decrease of tyrosine phosphorylation of p93, p175, and p220/230,
      indicating that dephosphorylation on protein tyrosine residues might be
      associated with calcium influx during physiological ARs as well. Proteins p93 and
      p175 were effectively solubilized in greater than 9M urea/1% triton and in SDS
      sample buffer, but to only a small extent in triton, while p20 was virtually
      completely extractable with triton. In conjunction with the previously reported
      isolation of active tyrosine kinase sp42 from triton extracts of noncapacitated
      boar sperm cells (Berruti and Porzio, 1992: Biochim Biophys Acta 1118: 149-154),
      our results suggest that a cAMP-dependent event is required for tyrosine
      phosphorylation of triton-insoluble proteins such as p93 and p175. On the other
      hand, the tyrosine phosphorylation of p20 (and potentially other triton-soluble
      substrates) might not strictly require such cAMP up-regulation. We discuss the
      differences in the regulation of cAMP-dependent tyrosine phosphorylation in
      mouse, human, and boar sperm, and suggest that sensitivity to calcium and
      distinct basal levels of cyclic nucleotide PDE might correspond to species
      specific reproduction strategies in mammals.

PMID- 9771652
TI  - Theca cells and theca-cell conditioned medium inhibit the progression of FSH
      induced meiosis of bovine oocytes surrounded by cumulus cells connected to
      membrana granulosa.
AB  - The effect of follicular cells and their conditioned media on the FSH-induced
      oocyte maturation of oocytes surrounded by cumulus cells connected to the
      membrana granulosa (COCGs) was investigated. COCGs and cumulus oocyte complexes
      (COCs) were cultured for 22 hr in M199 supplemented with 0.05 IU FSH/ml in either
      the presence of pieces of theca cell layer or in the presence of pieces of
      membrana granulosa. COCGs and COCs were also cultured for 22 hr in either theca
      cell conditioned medium (CMt) or in granulosa cell conditioned medium (CMg), both
      supplemented with 0.05 IU FSH/ml. To investigate the importance of cell-cell
      contacts between granulosa cells and cumulus cells, oocytes were cultured as COCs
      in CMt, as COCs in CMt supplemented with pieces of membrana granulosa, or as
      COCGs in CMt. In all groups the medium was supplemented with 0.05 IU FSH/ml.
      After culture the nuclear status of the oocytes was assessed using orcein
      staining. Culture of COCGs in the presence of theca cells as well as in CMt
      resulted in a significantly decreased proportion of oocytes that had undergone
      germinal vesicle breakdown (GVBD) at the end of the culture period as compared to
      the control. Of the oocytes that resumed meiosis in the presence of theca cells
      or in CMt, the proportion of oocytes that progressed up to the MII stage was
      significantly reduced. This indicates the production of a meiosis-inhibiting
      factor by theca cells. Culture with COCs instead of COCGs resulted in comparable
      results although the effect was less pronounced. The significant effect on the
      progression of meiosis of oocytes cultured as COCGs or as COCs, obtained in the
      presence of granulosa cells or in CMg, was much weaker than the effect of theca
      cells or culture in CMt. Culture of COCs in CMt supplemented with layers of
      membrana granulosa and 0.05 IU FSH/ml, resulted in significantly less oocytes
      that resumed meiosis as compared to culture of COCs in CMt. Of the oocytes that
      showed GVBD, the proportion that progressed up to the MII stage was significantly
      reduced. Attachment of the COCs to the membrana granulosa enhanced this
      inhibiting action of CMt on the progression of meiosis. It is concluded that
      theca cells secrete a stable factor that inhibits the progression of FSH-mediated
      meiosis in oocytes of COCGs.

PMID- 9771653
TI  - Sequence and analysis of zona pellucida 2 cDNA (ZP2) from a marsupial, the
      brushtail possum, Trichosurus vulpecula.
AB  - All mammalian eggs are surrounded by the zona pellucida, an extracellular coat
      involved in vital functions during fertilization and early development. The zona
      pellucida glycoproteins are promising antigenic targets for development of
      contraceptive vaccines to control pest populations of marsupials in Australia and
      New Zealand. Our current understanding of the function of the zona pellucida
      glycoproteins is based almost entirely on the mouse and may not be representative
      of gamete interactions in all eutherian or marsupial mammals. This study reports
      the isolation and characterization of the ZP2 gene from the brushtail possum
      (Trichosurus vulpecula). The brushtail possum ZP2 mRNA is 2,182 nucleotides long
      with an open reading frame coding for a polypeptide chain of 712 amino acids with
      a molecular mass of 79,542 d. The deduced amino acid sequence of possum ZP2 is 48
      to 55% identical to that of eutherian mammals. It shares several structural
      characteristics including N-linked glycosylation sites, location and number of
      cysteine residues, and hydropathy profile. The brushtail possum ZP2 gene is
      expressed exclusively in the ovary. Further studies are planned to elucidate the
      specific site of ZP2 expression within the ovary and its function during
      fertilization in marsupials.

PMID- 9771654
TI  - Changes in the bovine zona pellucida induced by plasmin or embryonic plasminogen
      activator.
AB  - Effects of bovine plasmin and plasminogen activator recovered from bovine embryo
      conditioned medium (bePA) on the polypeptide profile and solubility of bovine
      zonae pellucidae (ZP) were evaluated. ZP were isolated from bovine ovarian
      oocytes and incubated at 39 degrees C with 0, 100, or 200 microg/ml plasmin for
      0, 24, or 48 hr or bePA with 0 or 100 microg/ml human plasminogen for 0 or 48 hr.
      ZP were evaluated either by SDS-PAGE or for changes in solubility using a zona
      pellucida dissolution time (ZPDT) assay. Two prominent polypeptides, molecular
      weight (MW) 76,000 and 65,000, and two minor polypeptides, MW 23,000 and 22,000,
      were resolved by SDS-PAGE. No changes occurred in the polypeptide profile for ZP
      incubated with 0 microg/ml plasmin for 0, 24, or 48 hr, and ZPDT did not differ
      (P > 0.10). Treatment with 100 or 200 microg/ml plasmin induced reductions in the
      MW 76,000, 23,000, and 22,000 polypeptides and the appearance of MW 45,000 and
      <10,000 polypeptides. ZPDT were less (P < 0.05) in 100 and 200 microg/ml compared
      with 0 microg/ml plasmin. Polypeptide profiles and ZPDT for ZP incubated with
      bePA were similar (P > 0.10) to ZP incubated with unconditioned medium. Addition
      of human plasminogen to ZP incubated with bePA reduced the MW 76,000, 23,000, and
      22,000 polypeptides, caused the appearance of MW 45,000 and 20,000 polypeptides,
      and decreased ZPDT (P < 0.05). These results demonstrate that bovine plasmin is
      capable of proteolytically degrading the bovine ZP and that bePA can indirectly
      affect the ZP by converting plasminogen to plasmin.

PMID- 9771655
TI  - Follicle-stimulating hormone and growth hormone act differently on nuclear
      maturation while both enhance developmental competence of in vitro matured bovine
      oocytes.
AB  - This study was designed to investigate the effect of follicle-stimulating hormone
      (FSH) on nuclear maturation, fertilization, and early embryonic development of in
      vitro-matured bovine oocytes and to find out whether this effect is exerted
      through a cyclic adenosine monophosphate (cAMP) signal transduction pathway. In
      addition the effect of the combination of FSH and growth hormone (GH) on
      subsequent cleavage and embryo development was studied. Therefore cumulus oocyte
      complexes were cultured in the presence of FSH (0.05 IU/ml) and the nuclear stage
      of the oocytes was assessed using 4,6-diamino-2-phenyl-indole (DAPI) staining
      either after 16, 20, or 24 hr of in vitro maturation or 18 hr after the onset of
      fertilization. To assess the effect of FSH and the combination of FSH and GH
      added during in vitro maturation on the developmental capacity of the oocytes,
      cumulus oocyte complexes were incubated in the presence of either FSH (0.05
      IU/ml) or FSH (0.05 IU/ml) plus GH (100 ng/ml) for 22 hr, followed by in vitro
      fertilization and in vitro embryo culture. To investigate whether FSH-induced
      oocyte maturation is exerted through the cAMP pathway, cumulus oocyte complexes
      were cultured in M199 supplemented with FSH (0.05 IU/ml) and H-89 (10 microM), a
      specific inhibitor of cAMP-dependent protein kinase A. After 16 hr of culture,
      the proportion of oocytes in metaphase II (MII) stage was determined. Cultures
      with GH and without FSH and H-89 served as controls. The percentage of MII
      oocytes at 16 hr of incubation was significantly lower (P < 0.001) in the
      presence of FSH than in the control group, while the number of MII oocytes beyond
      20 hr did not differ from the control group. That points to a transient
      inhibition of nuclear maturation by FSH. Opposite to FSH, addition of GH during
      in vitro maturation significantly enhanced the number of MII oocytes after 16 hr
      of culture (P < 0.001), which points to the acceleration of nuclear maturation by
      GH. Addition of FSH during in vitro maturation significantly enhanced the
      proportion of normal fertilized oocytes, cleaved embryos and blastocysts (P <
      0.001). Similarly, addition of GH during in vitro maturation significantly
      enhanced the number of cleaved embryos and blastocysts (P < 0.001); however, in
      vitro maturation in the presence of GH and FSH did not result in an extra
      enhancement of the embryo development. Both the inhibition of nuclear maturation
      by FSH and its acceleration by GH was completely abolished by H-89. In
      conclusion, in vitro maturation of bovine oocytes in the presence of FSH retards
      nuclear maturation via a cAMP-mediated pathway, while it enhances fertilizability
      and developmental ability of the oocytes. Supplementation of GH and FSH during in
      vitro maturation did not result in an extra increase in the number of blastocysts
      following in vitro fertilization and in vitro embryo culture.

PMID- 9771656
TI  - Functional analysis of activation of porcine oocytes by spermatozoa, calcium
      ionophore, and electrical pulse.
AB  - The present study was conducted to examine differences in the activation of pig
      oocytes induced by sperm penetration or the artificial stimulators calcium
      ionophore A23187 and electrical pulse. Cumulus-oocyte complexes were cultured in
      NCSU 23 medium supplemented with 10% pig follicular fluid and 0.57 mM cysteine
      for 44 hr and then freed from cumulus and corona cells prior to activation with
      A23187 or an electrical pulse or inseminated with frozen-thawed ejaculated semen.
      Cortical granule (CG) exocytosis, zona reaction, nuclear activation, and
      developmental ability were examined after treatment. A23187 and electrical pulse
      induced 75.7% and 76.9% of CGs to be released from oocytes. Sperm penetration
      induced 86.3% of CGs to be released from the oocytes, which was significantly
      higher (P < 0.05) than those induced by artificial stimulators. Activation
      induced by A23187 and sperm penetration resulted in a zona reaction, which
      prevented sperm penetration after insemination or reinsemination, respectively.
      Activation induced by electrical pulse, however, did not cause a zona block since
      the penetration rate (80%) of oocytes was not different (P > 0.05) from that in
      control oocytes (87%). Electrical pulse induced 87% of the oocytes to form a
      pronucleus(ei), with 53% failing to release the second polar body. A23187 induced
      62% of oocytes to form a pronucleus(ei), and 81% of these oocytes released the
      second polar body. Sperm penetration induced 98-100% of the oocytes to release
      the second polar body and form a female pronucleus, and 88-89% of sperm
      penetrated oocytes formed a male pronucleus(ei). Blastocyst formation of oocytes
      exposed to spermatozoa, electrical pulse, and A23187 was 27%, 10%, and 4% at Day
      6 and 28%, 11%, and 5% at Day 7, respectively (P < 0.05). More nuclei were
      observed in the blastocysts derived from in vitro fertilization (32.3 +/- 12.9)
      than artificial stimulators. These results indicate that different and possibly
      overlapping mechanisms may be involved in the activation of pig oocytes by
      spermatozoa, electrical pulse, and A23187.

PMID- 9771657
TI  - Neurophysiologic evaluation and clinical trials for neuromuscular diseases.

PMID- 9771658
TI  - Electrophysiological monitoring in clinical trials. Roche Neuropathy Study Group.
AB  - Electrophysiological testing remains an important efficacy parameter in clinical
      neuropathy trials. The quality of nerve conduction studies in reported trials
      varies greatly, and may be responsible for negative results. We report the
      utilization of an expert core lab for electrophysiological testing. With the core
      lab, the variability of repeat testing is comparable to that of a single,
      excellent laboratory. Motor conduction velocities demonstrated a coefficient of
      variation of 3% and sensory conduction velocities 4% across 60 study sites. The
      distal motor evoked potential amplitudes varied by 13% at the ankle, and 10% at
      the wrist. The sensory potential amplitudes varied by 16% at the ankle, and 11%
      at the wrist in 60 sites. The overall monitoring rate in all submitted nerve
      conduction tracings was 36.6%. Our results show that an expert core lab can
      improve the electrophysiological quality of clinical trial data with the
      potential to show small changes in nerve conduction velocities and in both motor
      and sensory potential amplitudes.

PMID- 9771659
TI  - Study of mitochondrial DNA depletion in muscle by single-fiber polymerase chain
      reaction.
AB  - We studied muscle biopsies from 3 children with a mitochondrial myopathy
      characterized histochemically by the presence of ragged-red fibers (RRF) and
      various numbers of cytochrome c oxidase (COX)-negative fibers. We quantitated the
      absolute amounts of total mitochondrial DNA (mtDNA) in isolated normal COX
      positive muscle fibers and in COX-negative RRF. There was severe mtDNA depletion
      in all fibers from the two most severe cases. In the third case mtDNA depletion
      could not be established with conventional diagnostic tools, but it was
      documented in single COX-negative fibers; COX-positive fibers showed the same
      amounts of mtDNA as fibers from aged-matched controls. Our observations indicate
      that mtDNA single-fiber PCR quantitation is a highly sensitive and specific
      method for diagnosing cases with focal mtDNA depletion. This method also allows
      one to correlate amounts of mtDNA with histochemical phenotypes in individual
      fibers from patients and age-matched controls, thereby providing important
      information about the functional role of residual mtDNA.

PMID- 9771660
TI  - Experimental muscle pain does not cause long-lasting increases in resting
      electromyographic activity.
AB  - The mutual links between muscle pain and resting electromyographic (EMG) activity
      are still controversial. This study described effects of experimental muscle pain
      on resting EMG activity in a jaw-closing muscle and a leg muscle. Pain was
      induced by injections of hypertonic saline into the muscles in 10 subjects.
      Injections of isotonic saline served as a control. The pain intensity was scored
      on visual analog scales (VAS) and surface and intramuscular wire EMGs were
      obtained from the resting muscles before, during, and after saline injections.
      EMG activity was analyzed in 30-s intervals and demonstrated, in both muscles,
      significant increases 30-60 s after injection of hypertonic saline, but not after
      injection of isotonic saline. In contrast to the transient increase in EMG
      activity, the pain sensation lasted up to 600 s after injection of hypertonic
      saline. It was concluded that acute muscle pain is unable to maintain longer
      lasting resting muscle hyperactivity.

PMID- 9771661
TI  - Overproduction of vascular endothelial growth factor/vascular permeability factor
      is causative in Crow-Fukase (POEMS) syndrome.
AB  - Crow-Fukase or POEMS syndrome of polyneuropathy, organomegaly, endocrinopathy, M
      protein, and skin changes is a rare multisystem disorder of obscure pathogenesis
      that is associated with microangiopathy, neovascularization, and accelerated
      vasopermeability. We examined the levels of the vascular endothelial growth
      factor/vascular permeability factor (VEGF) in the serum and cerebrospinal fluid
      (CSF) from 10 patients with this syndrome. Serum VEGF levels were about 15-30
      times those in control subjects or patients with Guillain-Barre syndrome (GBS),
      chronic inflammatory demyelinating polyneuropathy (CIDP), and other neurological
      disorders. The CSF VEGF levels, however, were similar to those found in GBS and
      CIDP. Elevated VEGF levels in the serum decreased in 7 patients with Crow-Fukase
      syndrome after conventional therapy. The principal isoform of VEGF in Crow-Fukase
      syndrome was VEGF165. Elevated VEGF was independent of M-protein. Our results
      suggest that the overproduction of VEGF is important in the pathogenesis of this
      disorder.

PMID- 9771662
TI  - Body mass index effect on common nerve conduction study measurements.
AB  - This study was performed to determine whether there is a difference in nerve
      conduction study (NCS) measures based on body fat (body mass index; BMI). Two
      hundred fifty-three subjects had the following NCS tests performed on them:
      median, ulnar, peroneal, and tibial motor studies; median, ulnar, radial, and
      sural sensory studies; median and ulnar mixed nerve studies; and H-reflex
      studies. BMI was calculated as weight (kg) divided by height (m) squared. A
      repeated measures analysis of variance was run adjusting for age, sex, and height
      and using BMI as both a continuous variable and by dividing BMI into upper,
      middle, and lower thirds. The sensory and mixed nerve amplitudes correlated
      significantly (P < or = 0.01) with BMI for all nerves tested, with means being
      approximately 20-40% lower in the obese than in the thin subjects. No correlation
      was noted between BMI and nerve conduction velocity, H-reflex latency, or most of
      the other motor/sensory/mixed measures. The correlation between increased BMI and
      lower sensory/mixed nerve amplitudes should be taken into account in clinical
      practice.

PMID- 9771663
TI  - Consistent repeated M- and H-Wave recording in the hind limb of rats.
AB  - Sensory and motor conduction velocities calculated from latencies of H reflexes
      and M waves in rat hind limbs have been used to assess experimental peripheral
      neuropathy. Amplitudes and latencies vary with recording location, and are seldom
      assessed directly. Using subcutaneous electrodes on the foot, we recorded
      consistent M waves and H reflexes while stimulating the sciatic or tibial nerve.
      The late wave disappeared when dorsal roots were cut, verifying that it was an H
      reflex. However, stimulus-response characteristics differed from those in humans:
      (a) the threshold was often higher than for M waves; (b) stimulus intensity
      eliciting a maximum H-reflex amplitude (Hmax) was often higher than adequate for
      a maximum M-wave amplitude; and (c) the amplitudes of H reflexes stimulated with
      intensities supramaximal for the M wave were over 90% of Hmax. H reflexes and M
      waves recorded repeatedly in rats can be useful in assessing sensory and motor
      function in models of neuropathy, using amplitudes as well as conduction
      velocities.

PMID- 9771664
TI  - High-temperature repetitive nerve stimulation in myasthenia gravis.
AB  - High temperature enhances the decrement on repetitive nerve stimulation (RNS) in
      patients with myasthenia gravis (MG). However, the limit of this phenomenon at
      high temperature is unknown. Three-hertz ulnar RNS was performed in 7 patients
      with MG at a skin temperature of 32 degrees C and then with the hand in a 44
      degrees C water bath. At 32 degrees C, the mean decrement preactivation was 5%
      (range, 0-24%); after 1 min of exercise, the mean decrement reached a maximum of
      11% (range, 1-34%) 2 min postactivation. At a hand temperature of 42 degrees C,
      the mean decrement preactivation was 17% (range, 0-65%); after exercise, the mean
      decrement reached a maximum of 29% (range, 5-74%) 1 min postactivation. In 3
      subjects, RNS was normal at 32 degrees C, but a definite decrement developed with
      heating. These findings demonstrate that very high temperature can improve the
      sensitivity of ulnar RNS for postsynaptic neuromuscular transmission defects.

PMID- 9771665
TI  - Major histocompatibility complex class II expression and macrophage responses in
      genetically proven Charcot-Marie-Tooth type 1 and hereditary neuropathy with
      liability to pressure palsies.
AB  - This study examined major histocompatibility complex (MHC) class II expression
      and macrophage infiltration in sural nerve biopsies from patients with
      genetically proven Charcot-Marie-Tooth (CMT) 1A and 1B and hereditary neuropathy
      with liability to pressure palsies (HNPP) by immunocytochemistry. In both young
      and older patients with duplication of the PMP22 gene, MHC class II expression
      was consistently up-regulated and not closely related to the extent of macrophage
      infiltration. On the other hand, MHC class II expression was more variable in
      CMT1A and CMT1B caused by point mutations and in HNPP. The extent of nerve
      pathology as assessed by teased fiber preparations or electron microscopy was not
      predictive for the degree of MHC class II expression in CMT1/HNPP. We conclude
      that MHC class II up-regulation is a common feature in hereditary neuropathies.
      As shown for the animal model of globoid cell dystrophy, it is conceivable that
      increased expression of MHC class II molecules in CMT1 and HNPP accelerates nerve
      pathology.

PMID- 9771666
TI  - An 8-year longitudinal study of muscle strength, muscle fiber size, and dynamic
      electromyogram in individuals with late polio.
AB  - Twenty-one subjects with polio 24 to 51 years prior to the first examination were
      studied on three occasions, each 4 years apart with measurements of muscle
      strength and endurance for knee extension, macro EMG, and muscle biopsy from
      vastus lateralis. On average the muscle strength decreased during the 8-year
      follow-up by 9-15%. Endurance decreased during the observation period. The muscle
      fiber area was markedly increased in most subjects. There was a decrease in the
      capillarization during the follow-up. Macro EMG was increased in all subjects
      (range 3-42 times control) and increased in 20 legs during the 8-year follow-up,
      but showed a decrease in 8 of 9 legs with an approximative breakpoint when macro
      MUPs were around 20 times the normal size. Thus, evidence of on-going
      denervation/reinnervation as well as of failing capacity to maintain large motor
      units was demonstrated. SFEMG showed a moderate degree of disturbed neuromuscular
      transmission.

PMID- 9771667
TI  - Mechanomyographic and electromyographic responses to eccentric and concentric
      isokinetic muscle actions of the biceps brachii.
AB  - The purpose of the present investigation was to examine the effects of forearm
      angular velocity on the mechanomyographic (MMG) and electromyographic (EMG)
      responses to eccentric and concentric isokinetic muscle actions. Ten adult male
      volunteers (mean+/-SD age=23+/-2 years) performed maximal eccentric and
      concentric muscle actions of the forearm flexors at 30 degrees, 90 degrees, and
      150 degrees s(-1). There was no significant (P> 0.05) velocity-related change in
      peak torque (PT) for the eccentric muscle actions, but there was a significant (P
      < 0.05) decrease in PT for the concentric muscle actions. For the eccentric and
      concentric muscle actions, there was a significant (P< 0.05) velocity-related
      increase in MMG amplitude. There was no significant (P < 0.05) change in EMG
      amplitude across velocity for the eccentric or concentric muscle actions. The
      results indicated velocity-related dissociations among the PT, MMG, and EMG
      responses to maximal eccentric and concentric isokinetic muscle actions.

PMID- 9771668
TI  - Central motor conduction time: reproducibility and discomfort of different
      methods.
AB  - Central motor conduction time, a useful measure for studying central motor
      pathways, is calculated by determining the difference between the latency of
      motor-evoked potentials and peripheral conduction time. The intraindividual trial
      to-trial variability of central motor conduction time and the discomfort
      associated with three methods of measuring peripheral motor conduction time (F
      wave latency, cervical magnetic stimulation, and cervical needle stimulation)
      were studied in 5 healthy subjects with the use of transcranial magnetic
      stimulation to elicit motor-evoked potentials. Central motor conduction time was
      calculated by using measurements, made on 3 separate days, from the same three
      muscles on each hand. A visual analog pain scale was used to determine the level
      of discomfort for each method. Intraindividual trial-to-trial variability of
      central motor conduction time was similar for all methods, with coefficients of
      variation of 13% for the F-wave latency, 15% for cervical magnetic stimulation,
      and 11% for cervical needle stimulation. The last method was significantly more
      painful than the other two methods; there was no significant difference in
      discomfort between the F-wave method and cervical magnetic stimulation. To assess
      peripheral motor conduction time, when determining central motor conduction time,
      either the F-wave method or cervical magnetic stimulation is preferable to
      cervical needle stimulation.

PMID- 9771669
TI  - Quantification of early damage in latissimus dorsi muscle grafts.
AB  - Acute damage in the latissimus dorsi muscle may account for variable clinical
      results following dynamic cardiomyoplasty and an ischemic cause has been
      suggested. Using established techniques, we set out to demonstrate and to
      quantify the acute muscle damage in a rodent model. The left latissimus dorsi
      muscle of 5 Sprague-Dawley rats was mobilized on its thoracodorsal vascular
      pedicle, thus interrupting the regional blood supply to its distal part. The
      undisturbed contralateral muscle served as a matched control. After 24 hours, the
      muscle was excised and divided into proximal, middle, and distal thirds. Damage
      was graded histologically and quantified by nitroblue tetrazolium
      macrohistochemistry. Both methods of assessment correlated well (r=-0.936; P <
      0.001) and demonstrated significant damage, principally in the middle and the
      distal regions of the ischemic muscles. Therefore, the rodent model appears to be
      useful for investigating the pathogenesis and prevention of acute ischemic damage
      in the latissimus dorsi graft under conditions resembling the clinical scenario.

PMID- 9771670
TI  - Doxorubicin chemomyectomy as a treatment for cervical dystonia: histological
      assessment after direct injection into the sternocleidomastoid muscle.
AB  - The sternocleidomastoid muscle (SCM) is one of the major muscles involved in
      producing abnormal head position in cervical dystonia patients. This study tested
      whether doxorubicin chemomyectomy, direct injection of doxorubicin into the SCM
      to permanently remove muscle fibers, has the potential to be a nonsurgical,
      permanent treatment for cervical dystonia. The right SCM of rabbits was injected
      with either 1 or 2 mg doxorubicin. Animals were sacrificed 1-2 months
      postinjection. The SCM was prepared for histological examination of muscle fiber
      loss and fiber type composition. In all cases, direct injection of doxorubicin
      resulted in significant decreases in total muscle cross-sectional areas ranging
      from 75% up to 98%. Individual myofiber cross-sectional areas were smaller than
      normal after 2 mg doxorubicin treatment, but similar to normal fiber size after 1
      mg doxorubicin. There were increased numbers of myofibers that expressed slow and
      neonatal myosin heavy chain isoforms in these remaining muscle fibers compared to
      the untreated SCM on the contralateral side. Developmental myosin heavy chain
      (MHC) was also present in 53% of the remaining myofibers of the treated muscles.
      The fiber type composition of muscles contralateral to the doxorubicin injections
      was compared to the fiber type composition of SCM from normal, untreated
      controls; no difference was seen in the proportions of fast, slow, and neonatal
      MHC fiber types in these SCM muscles. In summary, the direct injection of
      doxorubicin into the SCM resulted in significant muscle loss. This supports the
      use of doxorubicin chemomyectomy as a potential permanent, nonsurgical treatment
      for cervical dystonia.

PMID- 9771671
TI  - Properties of Ca2+-activated K+ channels in erythrocytes from patients with
      myotonic muscular dystrophy.
AB  - Using the single-channel patch-clamp technique, Ca2+-activated K+ channels of
      erythrocytes from patients with myotonic muscular dystrophy (MyD) were studied.
      Elementary single-channel properties--conductance, rectification, kinetics,
      voltage- and calcium-dependence--measured in inside-out patches of MyD
      erythrocytes, did not differ significantly from those of control cells. The
      activity of the channels, studied in patches attached to red cells from MyD
      patients, exhibited mean patch currents which were significantly higher than the
      controls. The increased mean patch current was due to a higher opening frequency,
      associated with a reduced mean channel closed time. These results indicate that
      Ca2+-activated K+ channels of erythrocytes from patients either detect a higher
      intracellular calcium concentration and/or express an augmented calcium
      sensitivity. Since these channels are targets for phosphorylation, our findings
      make it possible to identify defective kinase mechanisms, in minimally disturbed
      cells of the patient, at a molecular level of resolution.

PMID- 9771672
TI  - Lethal neonatal autosomal recessive axonal sensorimotor polyneuropathy.
AB  - Peripheral neuropathy is an uncommon cause of generalized hypotonia and weakness
      in infancy. It occurs as a part of the clinical syndrome in some
      neurodegenerative disorders of infancy, but seldom causes respiratory failure or
      swallowing difficulties. We report a lethal autosomal recessive axonal
      polyneuropathy with neonatal onset in a large kindred from Northern Mississippi.
      One patient was studied in detail at our medical center and the information on 12
      other affected infants in this large family were gathered from medical records
      and by interviewing the family members. Patients were symptomatic for the
      polyneuropathy before birth and died in the first year of life from respiratory
      complications. Thirteen babies were affected by this clinical phenotype in four
      generations of this family with a high frequency of consanguinity. Affected
      babies were of both sexes and were born to healthy consanguineous parents. The
      clinical phenotype of polyneuropathy in our index patient and other affected
      babies in this family was similar, and represents a unique form of hereditary
      neonatal polyneuropathy.

PMID- 9771673
TI  - Transthyretin Tyr77 familial amyloid polyneuropathy: a clinicopathological study
      of a large kindred.
AB  - More than 40 point mutations (producing different clinical manifestations) have
      been described in diverse points of the plasma protein transthyretin (TTR). The
      Met30 is considered the most common mutation, the Tyr77 mutation being the second
      most prevalent. However, data from patients with this late mutation are scarce,
      and usually come from isolated case reports or tables. The Tyr77 mutation is not
      as well characterized as the Met30 mutation, especially with respect to such
      aspects as prognosis or possible treatment by liver transplantation. We therefore
      present the clinical and pathological features of an extensive family with the
      Tyr77 TTR mutation, comprising 12 affected individuals over four generations. Six
      living individuals were followed over a 10-year period. Retrospective data were
      obtained with regard to the deceased family members. We found that an initial and
      sometimes prolonged carpal tunnel syndrome, beginning between the 6th and 7th
      decades, characterizes the Tyr77 mutation. In most cases this evolved to
      generalized peripheral nerve involvement, restrictive cardiomyopathy, and
      intestinal malabsortion. Although survival is usually high, there are progressive
      cases that should be candidates for liver transplant, before severe impairment
      has developed.

PMID- 9771674
TI  - Vasomotor and sudomotor function in the hand after thoracoscopic transection of
      the sympathetic chain: implications for choice of therapeutic strategy.
AB  - The degree of sympatholysis achieved by thoracoscopic transection of the
      sympathetic chain (sympathicotomy) was evaluated by measuring sudo- and vasomotor
      function in the hands before and after surgery in 12 patients with palmar
      hyperhidrosis. Our results show a marked reduction in sweat production and a
      cutaneous vasodilatation which remained unchanged during the 6 months follow-up,
      whereas sudo- and vasomotor reflexes normalized within this time. Skin
      temperature variations did not correlate to skin perfusion changes. Since all
      subjects reported dry and warm hands throughout the follow-up period, our results
      indicate that recording reflex responses to sympathoexcitatory stimuli does not
      adequately reflect clinical outcome of subtotal sympatholytic procedures
      performed for hyperhidrosis. Monitoring of clinical outcome should therefore
      include measurement of baseline sweat production and skin perfusion. However, the
      normalized reflex responses highlight the incomplete sympatholysis achieved by
      thoracoscopic sympathicotomy, which may be beneficial in some pathological
      conditions (such as hyperhidrosis) but detrimental in others.

PMID- 9771675
TI  - Clinical, pathological, and genetic features of limb-girdle muscular dystrophy
      type 2A with new calpain 3 gene mutations in seven patients from three Japanese
      families.
AB  - We report on the clinical, pathological, and genetic features of 7 patients with
      limb-girdle muscular dystrophy type 2A (LGMD2A) from three Japanese families. The
      mean age of onset was 9.7+/-3.1 years (mean+/-SD), and loss of ambulance occurred
      at 38.5+/-2.1 years. Muscle atrophy was predominant in the pelvic and shoulder
      girdles, and proximal limb muscles. Muscle pathology revealed dystrophic changes.
      In two families, an identical G to C mutation at position 1080 the in calpain 3
      gene was identified, and a frameshift mutation (1796insA) was found in the third
      family. The former mutation results in a W360R substitution in the proteolytic
      site of calpain 3, and the latter in a deletion of the Ca2+-binding domain.

PMID- 9771676
TI  - Motor unit discharge behaviors in stroke patients.
AB  - We studied 60 motor units from abductor pollicis brevis, first dorsal
      interosseous, and abductor digiti minimus muscles in 18 patients with upper motor
      neuron lesions. Both fractional process parameters and serial correlation
      coefficients were estimated. The results suggest that both serial correlation
      coefficients and fractional process parameters can be used to objectively
      document upper motor neuron disorders in stroke patients. However, each of them
      may be more sensitive to distinct central motor regulatory mechanisms.

PMID- 9771677
TI  - Cold preserved nerve allografts: changes in basement membrane, viability,
      immunogenicity, and regeneration.
AB  - Rat sciatic nerve graft segments were harvested and pretreated by either
      placement in the University of Wisconsin Cold Storage Solution at 5 degrees C and
      storage from 1 to 26 weeks, or repeatedly freezing (-40 degrees C) and thawing
      (20 degrees C). Following pretreatment, grafts were transplanted as either
      syngeneic or allogeneic nerve grafts. Storage and freeze-thawing did not affect
      the Schwann cell basal lamina or laminin distribution of the peripheral nerve.
      Graft cell viability decreased with increasing time of storage, with some viable
      cells detectable even after 3 weeks of storage. Freeze-thawed grafts were not
      viable. Increasing time of storage led to decreasing immune response and graft
      rejection, but improved regeneration. Freeze-thawed and 26-week stored allografts
      were nonimmunogenic and rejection was not seen, but regeneration was delayed
      compared to autografts. Graft storage may become a useful adjunct to clinical
      nerve allografting to permit elective scheduling of surgery, provide greater time
      for preoperative tissue testing, and possibly blunt the immune response.

PMID- 9771678
TI  - Intracellular phosphates in inclusion body myositis--a 31P magnetic resonance
      spectroscopy study.
AB  - Muscle phosphorus magnetic resonance spectroscopy was used to study oxidative
      metabolism at rest and during recovery from exercise in 7 patients with sporadic
      inclusion body myositis (s-IBM), compared with normal controls (n=8) and
      mitochondrial myopathies (n=20). At rest, 6/7 patients had elevated inorganic
      phosphates. Recovery parameters were not different from controls, in contrast
      with mitochondrial myopathies, who showed abnormal rest and recovery. The normal
      recovery suggests that mitochondrial oxidative capacity is not impaired in s-IBM.

PMID- 9771679
TI  - Treatment of mononeuropathy multiplex in hepatitis C virus and cryoglobulinemia.
AB  - Recent reports advocate alpha-interferon (alpha-Ifn) treatment for mononeuropathy
      multiplex in hepatitis C virus-associated cryoglobulinemia. We report 2 patients
      with this disorder to describe two underrecognized treatment outcomes--worsening
      of polyneuropathy with initiation of alpha-Ifn, in the absence of
      immunosuppression, and deterioration of liver function with prednisone, despite
      improvement of polyneuropathy.

PMID- 9771680
TI  - Sodium withdrawal contractures in developing and regenerating rat extensor
      digitorum longus muscles.
AB  - During postnatal development of extensor digitorum longus (EDL) muscle, sodium
      withdrawal contractures were observed during the first 6 days after birth, and
      not after this time. In regenerating EDL muscles, zero-Na contractures were
      demonstrated: (1) 7 days after bupivacaine injection, but not 14 or 90 days after
      this injection; (2) 7, 14, and 90 days after autotransplantation; and (3) 7, 14,
      and 90 days after the intervention in sliced muscles. The present findings
      emphasize the role of the denervation in the development of zero-Na contractures
      in the regenerating muscles and suggest that a calcium-sodium exchange across the
      sarcolemma may appear in these muscles.

PMID- 9771681
TI  - Is there a familial carpal tunnel syndrome? An evaluation and literature review.
AB  - We review the reports of families proposed to have the familial carpal tunnel
      syndrome (FCTS). The demographic features of sporadic carpal tunnel syndrome
      (CTS) differ from FCTS, where an earlier onset and increased bilateral
      involvement is seen. We also identify seven new potential FCTS pedigrees on the
      basis of their having four or more members with symptoms suggesting CTS. In all
      but two pedigrees an explanation other than FCTS was found. We conclude that the
      FCTS is a rare, but genetically distinct disorder.

PMID- 9771682
TI  - Repetitive axonal stimulation of the same single motor unit: a longitudinal
      tracking study.
AB  - We elicited three single motor unit action potentials (S-MUAPs) via multiple
      point stimulation and subjected them to repetitive stimulation (RS) in 3 healthy
      subjects. We tracked each S-MUAP and its RS trains over two separate sessions as
      well as the compound motor action potential (CMAP) RS trains obtained from the
      same muscle following whole nerve stimulation. Repetitive axonal stimulation
      yields consistent results when carefully performed with minimal variation in each
      S-MUAP RS train from session to session, providing previously unobtainable data
      regarding neuromuscular junction function in the same single motor unit over
      time. In this small, normative sample, no significant correlation between S-MUAP
      and CMAP RS responses was observed.

PMID- 9771683
TI  - Intrasphincteric injection of botulinum toxin is effective in long-term treatment
      of esophageal achalasia.
AB  - We investigated the long-term efficacy and safety of intrasphincteric injections
      of botulinum toxin (100 U) in 57 patients with esophageal achalasia. One month
      after treatment, 50 patients had improved (88%); both symptom score and LES
      pressure were significantly reduced (P < 0.001). After a mean follow-up of 24+/
      15 months (range 6-48), 43 patients (75%) are still in remission, although repeat
      injections of toxin were needed to achieve a stable effect on symptoms.

PMID- 9771684
TI  - Early diagnosis of carpal tunnel syndrome: comparison of sensory conduction
      studies of four fingers.
AB  - Sensory studies of four fingers were performed on 72 patients with early (distal
      motor latency <4.2 ms) carpal tunnel syndrome (CTS) and on 43 control subjects.
      Results demonstrate that sensory studies of digit 4 yields the highest
      sensitivity (88%) for diagnosis of early CTS. The sensitivity of digit 1, digit
      2, and digit 3 was 61%, 22%, and 50%, respectively.

PMID- 9771685
TI  - Significance of passively induced stretch reflexes on achilles tendon force
      enhancement.
AB  - An in vivo buckle transducer technique was applied to study the reflex
      contribution to ATF enhancement during passive dorsiflexion stretches. Single
      stretches led to a linear ATF increase in the absence of an EMG reflex response,
      whereas clear ATF enhancement over the passive component occurred 13-15 ms after
      the onset of EMG responses. To quantify the reflexly induced increase in ATF, the
      stretched position was maintained. The mean reflex effect was two to four times
      greater than the passive stretch effect.

PMID- 9771687
TI  - The value of inching techniques in the diagnosis of focal nerve lesions. Inching
      is a useful technique.

PMID- 9771686
TI  - Primary alpha-sarcoglycan deficiency responsive to immunosuppression over three
      years.
AB  - An 8-year-old girl developed weakness over 2 years and an elevated creatine
      kinase. The biopsy was most consistent with an active dystrophy with many
      inflammatory cells present. A trial of immunosuppression was started. In the
      first 2 months of treatment with prednisone, she had functionally and
      quantitatively significant improvement in her proximal strength. Over 3 years of
      treatment she maintained stable strength. Subsequent genetic studies showed that
      she had primary alpha-sarcoglycan deficiency. The timing and the degree of
      benefit in strength were similar to that seen in boys with Duchenne muscular
      dystrophy who are treated with prednisone.

PMID- 9771688
TI  - The value of inching techniques in the diagnosis of focal nerve lesions. Inching
      techniques are of limited use.

PMID- 9771689
TI  - Needle muscle biopsy.

PMID- 9771690
TI  - Jitter measurement by axonal microstimulation in cervical radiculopathy.

PMID- 9771691
TI  - The calcium channel blocker verapamil in hypokalemic periodic paralysis.

PMID- 9771692
TI  - Genome vikings.

PMID- 9771693
TI  - Why commonplace encounters turn to fatal attraction.

PMID- 9771694
TI  - The centrosome--a tiny organelle with big potential.

PMID- 9771695
TI  - From a DNA helicase to brittle hair.

PMID- 9771696
TI  - The genetics of motherhood.

PMID- 9771697
TI  - Should the master regulator Rest in peace?

PMID- 9771698
TI  - A frameshift mutation in MC4R associated with dominantly inherited human obesity.

PMID- 9771699
TI  - A frameshift mutation in human MC4R is associated with a dominant form of
      obesity.

PMID- 9771700
TI  - The premature ageing syndrome protein, WRN, is a 3'-->5' exonuclease.

PMID- 9771701
TI  - Transcription of IAP endogenous retroviruses is constrained by cytosine
      methylation.

PMID- 9771702
TI  - Genetics and insurance in Britain: why more than just the Atlantic divides the
      English-speaking nations.
AB  - The British Government's official advisory committee on genetics has recommended
      a moratorium on the disclosure of genetic test results for life insurance until
      predictions based on such tests can be validated as actuarially important. In
      contrast, the trade association of the British insurance industry believes that
      genetic tests relating to eight conditions can yield information useful for life
      insurance. Although the Government has yet to respond, the debate is already
      moving on to genetic testing and the funding of health care for the elderly.

PMID- 9771703
TI  - A new logic for DNA engineering using recombination in Escherichia coli.
AB  - A straightforward way to engineer DNA in E. coli using homologous recombination
      is described. The homologous recombination reaction uses RecE and RecT and is
      transferable between E. coli strains. Several target molecules were manipulated,
      including high copy plasmids, a large episome and the E. coli chromosome.
      Sequential steps of homologous or site-specific recombination were used to
      demonstrate a new logic for engineering DNA, unlimited by the disposition of
      restriction endonuclease cleavage sites or the size of the target DNA.

PMID- 9771704
TI  - Host response to EBV infection in X-linked lymphoproliferative disease results
      from mutations in an SH2-domain encoding gene.
AB  - X-linked lymphoproliferative syndrome (XLP or Duncan disease) is characterized by
      extreme sensitivity to Epstein-Barr virus (EBV), resulting in a complex phenotype
      manifested by severe or fatal infectious mononucleosis, acquired
      hypogammaglobulinemia and malignant lymphoma. We have identified a gene, SH2D1A,
      that is mutated in XLP patients and encodes a novel protein composed of a single
      SH2 domain. SH2D1A is expressed in many tissues involved in the immune system.
      The identification of SH2D1A will allow the determination of its mechanism of
      action as a possible regulator of the EBV-induced immune response.

PMID- 9771705
TI  - NRSF/REST is required in vivo for repression of multiple neuronal target genes
      during embryogenesis.
AB  - The neuron-restrictive silencer factor NRSF (also known as REST and XBR) can
      silence transcription from neuronal promoters in non-neuronal cell lines, but its
      function during normal development is unknown. In mice, a targeted mutation of
      Rest, the gene encoding NRSF, caused derepression of neuron-specific tubulin in a
      subset of non-neural tissues and embryonic lethality. Mosaic inhibition of NRSF
      in chicken embryos, using a dominant-negative form of NRSF, also caused
      derepression of neuronal tubulin, as well as of several other neuronal target
      genes, in both non-neural tissues and central nervous system neuronal
      progenitors. These results indicate that NRSF is required to repress neuronal
      gene expression in vivo, in both extra-neural and undifferentiated neural tissue.

PMID- 9771706
TI  - A gene encoding a transmembrane protein is mutated in patients with diabetes
      mellitus and optic atrophy (Wolfram syndrome).
AB  - Wolfram syndrome (WFS; OMIM 222300) is an autosomal recessive neurodegenerative
      disorder defined by young-onset non-immune insulin-dependent diabetes mellitus
      and progressive optic atrophy. Linkage to markers on chromosome 4p was confirmed
      in five families. On the basis of meiotic recombinants and disease-associated
      haplotypes, the WFS gene was localized to a BAC/P1 contig of less than 250 kb.
      Mutations in a novel gene (WFS1) encoding a putative transmembrane protein were
      found in all affected individuals in six WFS families, and these mutations were
      associated with the disease phenotype. WFS1 appears to function in survival of
      islet beta-cells and neurons.

PMID- 9771707
TI  - Inversin, a novel gene in the vertebrate left-right axis pathway, is partially
      deleted in the inv mouse.
AB  - Visceral left-right asymmetry occurs in all vertebrates, but the inversion of
      embryo turning (inv) mouse, which resulted following a random transgene
      insertion, is the only model in which these asymmetries are consistently
      reversed. We report positional cloning of the gene underlying this recessive
      phenotype. Although transgene insertion was accompanied by neighbouring deletion
      and duplication events, our YAC phenotype rescue studies indicate that the mutant
      phenotype results from the deletion. After extensively characterizing the 47-kb
      deleted region and flanking sequences from the wild-type mouse genome, we found
      evidence for only one gene sequence in the deleted region. We determined the full
      length 5.5-kb cDNA sequence and identified 16 exons, of which exons 3-11 were
      eliminated by the deletion, causing a frameshift. The novel gene specifies a 1062
      aa product with tandem ankyrin-like repeat sequences. Characterization of
      complementing and non-complementing YAC transgenic families revealed that
      correction of the inv mutant phenotype was concordant with integration and intact
      expression of this novel gene, which we have named inversin (Invs).

PMID- 9771708
TI  - Mutations in orthologous genes in human spondyloepimetaphyseal dysplasia and the
      brachymorphic mouse.
AB  - The osteochondrodysplasias are a genetically heterogeneous group of disorders
      affecting skeletal development, linear growth and the maintenance of cartilage
      and bone. We have studied a large inbred Pakistani family with a distinct form of
      recessively inherited spondyloepimetaphyseal dysplasia (SEMD) and mapped a gene
      associated with this dwarfing condition to chromosome 10q23-24, a region syntenic
      with the locus for the brachymorphic mutation on mouse chromosome 19. We
      identified two orthologous genes, ATPSK2 and Atpsk2, encoding novel ATP
      sulfurylase/APS kinase orthologues in the respective regions of the human and
      mouse genomes. We characterized a nonsense mutation in ATPSK2 in the SEMD family
      and a missense mutation in the region of Atpsk2 encoding the APS kinase activity
      in the brachymorphic mouse. ATP sulfurylase/APS kinase catalyses the metabolic
      activation of inorganic sulfate to PAPS, the universal donor for post
      translational protein sulfation in all cell types. The cartilage-specificity of
      the human and mouse phenotypes provides further evidence of the critical role of
      sulfate activation in the maturation of cartilage extracellular matrix molecules
      and the effect of defects in this process on the architecture of cartilage and
      skeletogenesis.

PMID- 9771709
TI  - Abnormal maternal behaviour and growth retardation associated with loss of the
      imprinted gene Mest.
AB  - Mest (also known as Peg1), an imprinted gene expressed only from the paternal
      allele during development, was disrupted by gene targeting in embryonic stem (ES)
      cells. The targeted mutation is imprinted and reversibly silenced by passage
      through the female germ line. Paternal transmission activates the targeted allele
      and causes embryonic growth retardation associated with reduced postnatal
      survival rates in mutant progeny. More significantly, Mest-deficient females show
      abnormal maternal behaviour and impaired placentophagia, a distinctive mammalian
      behaviour. Our results provide evidence for the involvement of an imprinted gene
      in the control of adult behaviour.

PMID- 9771710
TI  - Mutations in a gene encoding a novel protein tyrosine phosphatase cause
      progressive myoclonus epilepsy.
AB  - Lafora's disease (LD; OMIM 254780) is an autosomal recessive form of progressive
      myoclonus epilepsy characterized by seizures and cumulative neurological
      deterioration. Onset occurs during late childhood and usually results in death
      within ten years of the first symptoms. With few exceptions, patients follow a
      homogeneous clinical course despite the existence of genetic heterogeneity.
      Biopsy of various tissues, including brain, revealed characteristic polyglucosan
      inclusions called Lafora bodies, which suggested LD might be a generalized
      storage disease. Using a positional cloning approach, we have identified at
      chromosome 6q24 a novel gene, EPM2A, that encodes a protein with consensus amino
      acid sequence indicative of a protein tyrosine phosphatase (PTP). mRNA
      transcripts representing alternatively spliced forms of EPM2A were found in every
      tissue examined, including brain. Six distinct DNA sequence variations in EPM2A
      in nine families, and one homozygous microdeletion in another family, have been
      found to cosegregate with LD. These mutations are predicted to cause deleterious
      effects in the putative protein product, named laforin, resulting in LD.

PMID- 9771711
TI  - Evidence for a prostate cancer susceptibility locus on the X chromosome.
AB  - Over 200,000 new prostate cancer cases are diagnosed in the United States each
      year, accounting for more than 35% of all cancer cases affecting men, and
      resulting in 40,000 deaths annually. Attempts to characterize genes predisposing
      to prostate cancer have been hampered by a high phenocopy rate, the late age of
      onset of the disease and, in the absence of distinguishing clinical features, the
      inability to stratify patients into subgroups relative to suspected genetic locus
      heterogeneity. We previously performed a genome-wide search for hereditary
      prostate cancer (HPC) genes, finding evidence of a prostate cancer susceptibility
      locus on chromosome 1 (termed HPC1; ref. 2). Here we present evidence for the
      location of a second prostate cancer susceptibility gene, which by heterogeneity
      estimates accounts for approximately 16% of HPC cases. This HPC locus resides on
      the X chromosome (Xq27-28), a finding consistent with results of previous
      population-based studies suggesting an X-linked mode of HPC inheritance. Linkage
      to Xq27-28 was observed in a combined study population of 360 prostate cancer
      families collected at four independent sites in North America, Finland and
      Sweden. A maximum two-point lod score of 4.60 was observed at DXS1113,
      theta=0.26, in the combined data set. Parametric multipoint and non-parametric
      analyses provided results consistent with the two-point analysis. Significant
      evidence for genetic locus heterogeneity was observed, with similar estimates of
      the proportion of linked families in each separate family collection. Genetic
      mapping of the locus represents an important initial step in the identification
      of an X-linked gene implicated in the aetiology of HPC.

PMID- 9771712
TI  - Holoprosencephaly due to mutations in ZIC2, a homologue of Drosophila odd-paired.
AB  - Holoprosencephaly (HPE) is the most common structural anomaly of the human brain
      and is one of the anomalies seen in patients with deletions and duplications of
      chromosome 13. On the basis of molecular analysis of a series of patients with
      hemizygous deletions of the long arm of chromosome 13, we have defined a discrete
      region in band 13q32 where deletion leads to major developmental anomalies (the
      13q32 deletion syndrome). This approximately 1-Mb region lies between markers
      D135136 and D13S147. Patients in which this region is deleted usually have major
      congenital malformations, including brain anomalies such as HPE or exencephaly,
      and digital anomalies such as absent thumbs. We now report that human ZIC2 maps
      to this critical deletion region and that heterozygous mutations in ZIC2 are
      associated with HPE. Haploinsufficiency for ZIC2 is likely to cause the brain
      malformations seen in 13q deletion patients.

PMID- 9771713
TI  - Mutations in the XPD helicase gene result in XP and TTD phenotypes, preventing
      interaction between XPD and the p44 subunit of TFIIH.
AB  - In most cases, xeroderma pigmentosum group D (XP-D) and trichothiodystrophy (TTD)
      patients carry mutations in the carboxy-terminal domain of the evolutionarily
      conserved helicase XPD, which is one of the subunits of the transcription/repair
      factor TFIIH (refs 1,2). In this study, we demonstrate that XPD interacts
      specifically with p44, another subunit of TFIIH, and that this interaction
      results in the stimulation of 5'-->3' helicase activity. Mutations in the XPD C
      terminal domain, as found in most patients, prevent the interaction with p44,
      thus explaining the decrease in XPD helicase activity and the nucleotide excision
      repair (NER) defect.

PMID- 9771714
TI  - Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy
      and transformation.
AB  - The centrosomes are thought to maintain genomic stability through the
      establishment of bipolar spindles during cell division, ensuring equal
      segregation of replicated chromosomes to two daughter cells. Deregulated
      duplication and distribution of centrosomes have been implicated in chromosome
      segregation abnormalities, leading to aneuploidy seen in many cancer cell types.
      Here, we report that STK15 (also known as BTAK and aurora2), encoding a
      centrosome-associated kinase, is amplified and overexpressed in multiple human
      tumour cell types, and is involved in the induction of centrosome duplication
      distribution abnormalities and aneuploidy in mammalian cells. STK15 amplification
      has been previously detected in breast tumour cell lines and in colon tumours;
      here, we report its amplification in approximately 12% of primary breast tumours,
      as well as in breast, ovarian, colon, prostate, neuroblastoma and cervical cancer
      cell lines. Additionally, high expression of STK15 mRNA was detected in tumour
      cell lines without evidence of gene amplification. Ectopic expression of STK15 in
      mouse NIH 3T3 cells led to the appearance of abnormal centrosome number
      (amplification) and transformation in vitro. Finally, overexpression of STK15 in
      near diploid human breast epithelial cells revealed similar centrosome
      abnormality, as well as induction of aneuploidy. These findings suggest that
      STK15 is a critical kinase-encoding gene, whose overexpression leads to
      centrosome amplification, chromosomal instability and transformation in mammalian
      cells.

PMID- 9771715
TI  - Nonsyndromic hearing impairment is associated with a mutation in DFNA5.
AB  - Nonsyndromic hearing impairment is one of the most heterogeneous hereditary
      conditions, with more than 40 loci mapped on the human genome, however, only a
      limited number of genes implicated in hearing loss have been identified. We
      previously reported linkage to chromosome 7p15 for autosomal dominant hearing
      impairment segregating in an extended Dutch family (DFNA5). Here, we report a
      further refinement of the DFNA5 candidate region and the isolation of a gene from
      this region that is expressed in the cochlea. In intron 7 of this gene, we
      identified an insertion/deletion mutation that does not affect intron-exon
      boundaries, but deletes five G-triplets at the 3' end of the intron. The mutation
      co-segregated with deafness in the family and causes skipping of exon 8,
      resulting in premature termination of the open reading frame. As no physiological
      function could be assigned, the gene was designated DFNA5.

PMID- 9771716
TI  - Behavioural abnormalities and selective neuronal loss in HD transgenic mice
      expressing mutated full-length HD cDNA.
AB  - Huntington disease (HD) is an adult-onset, autosomal dominant inherited human
      neurodegenerative disorder characterized by hyperkinetic involuntary movements,
      including motor restlessness and chorea, slowing of voluntary movements and
      cognitive impairment. Selective regional neuron loss and gliosis in striatum,
      cerebral cortex, thalamus, subthalamus and hippocampus are well recognized as
      neuropathological correlates for the clinical manifestations of HD. The
      underlying genetic mutation is the expansion of CAG trinucleotide repeats (coding
      for polyglutamines) to 36-121 copies in exon 1 of the HD gene. The HD mRNA and
      protein product (huntingtin) show widespread distribution, and thus much remains
      to be understood about the selective and progressive neurodegeneration in HD. To
      create an experimental animal model for HD, transgenic mice were generated
      showing widespread expression of full-length human HD cDNA with either 16, 48 or
      89 CAG repeats. Only mice with 48 or 89 CAG repeats manifested progressive
      behavioural and motor dysfunction with neuron loss and gliosis in striatum,
      cerebral cortex, thalamus and hippocampus. These animals represent clinically
      relevant models for HD pathogenesis, and may provide insights into the underlying
      pathophysiological mechanisms of other triplet repeat disorders.

PMID- 9771717
TI  - Circular chromosome formation in a fission yeast mutant defective in two ATM
      homologues.
AB  - Telomeres, found at chromosomal ends, are essential for stable maintenance of
      linear chromosomes in eukaryotes. The ATM family of genes, including budding
      yeast TEL1 (refs 1,2), fission yeast rad3+ (ref. 3) and human ATM (ref. 4), have
      been reported to be involved in telomere length regulation, although the
      significance of the telomere phenotypes observed with the mutated genes remains
      elusive. We have cloned tel1+, another fission yeast ATM homologue, and found
      that a tel1rad3 double mutant lost all telomeric DNA sequences. Thus, the ATM
      homologues are essential in telomere maintenance. The mutant grew poorly and
      formed irregular-shaped colonies, probably due to chromosome instability,
      however, during prolonged culture of the double mutant, cells forming normal
      round-shaped colonies arose at a relatively high frequency. All three chromosomes
      in these derivative cells were circular and lacked telomeric sequences. To our
      knowledge, this is the first report of eukaryotic cells whose chromosomes are all
      circular. Upon meiosis, these derivative cells produced few viable spores.
      Therefore, the exclusively circular genome lacking telomeric sequences is
      proficient for mitotic growth, but does not permit meiosis.

PMID- 9771718
TI  - High resolution analysis of DNA copy number variation using comparative genomic
      hybridization to microarrays.
AB  - Gene dosage variations occur in many diseases. In cancer, deletions and copy
      number increases contribute to alterations in the expression of tumour-suppressor
      genes and oncogenes, respectively. Developmental abnormalities, such as Down,
      Prader Willi, Angelman and Cri du Chat syndromes, result from gain or loss of one
      copy of a chromosome or chromosomal region. Thus, detection and mapping of copy
      number abnormalities provide an approach for associating aberrations with disease
      phenotype and for localizing critical genes. Comparative genomic hybridization
      (CGH) was developed for genome-wide analysis of DNA sequence copy number in a
      single experiment. In CGH, differentially labelled total genomic DNA from a
      'test' and a 'reference' cell population are cohybridized to normal metaphase
      chromosomes, using blocking DNA to suppress signals from repetitive sequences.
      The resulting ratio of the fluorescence intensities at a location on the
      'cytogenetic map', provided by the chromosomes, is approximately proportional to
      the ratio of the copy numbers of the corresponding DNA sequences in the test and
      reference genomes. CGH has been broadly applied to human and mouse malignancies.
      The use of metaphase chromosomes, however, limits detection of events involving
      small regions (of less than 20 Mb) of the genome, resolution of closely spaced
      aberrations and linking ratio changes to genomic/genetic markers. Therefore, more
      laborious locus-by-locus techniques have been required for higher resolution
      studies. Hybridization to an array of mapped sequences instead of metaphase
      chromosomes could overcome the limitations of conventional CGH (ref. 6) if
      adequate performance could be achieved. Copy number would be related to the
      test/reference fluorescence ratio on the array targets, and genomic resolution
      could be determined by the map distance between the targets, or by the length of
      the cloned DNA segments. We describe here our implementation of array CGH. We
      demonstrate its ability to measure copy number with high precision in the human
      genome, and to analyse clinical specimens by obtaining new information on
      chromosome 20 aberrations in breast cancer.

PMID- 9771720
TI  - A duty to publish.

PMID- 9771719
TI  - Targeted gene knockout mediated by triple helix forming oligonucleotides.
AB  - Triple helix forming oligonucleotides (TFOs) recognize and bind sequences in
      duplex DNA and have received considerable attention because of their potential
      for targeting specific genomic sites. TFOs can deliver DNA reactive reagents to
      specific sequences in purified chromosomal DNA (ref. 4) and nuclei. However,
      chromosome targeting in viable cells has not been demonstrated, and in vitro
      experiments indicate that chromatin structure is incompatible with triplex
      formation. We have prepared modified TFOs, linked to the DNA-crosslinking reagent
      psoralen, directed at a site in the Hprt gene. We show that stable Hprt-deficient
      clones can be recovered following introduction of the TFOs into viable cells and
      photoactivation of the psoralen. Analysis of 282 clones indicated that 85%
      contained mutations in the triplex target region. We observed mainly deletions
      and some insertions. These data indicate that appropriately constructed TFOs can
      find chromosomal targets, and suggest that the chromatin structure in the target
      region is more dynamic than predicted by the in vitro experiments.

PMID- 9771721
TI  - Rifampicin: a glucocorticoid receptor ligand?

PMID- 9771722
TI  - Clarifying AIDS vaccine trial guidelines.

PMID- 9771723
TI  - Calcineurin inhibitors and cardiac hypertrophy.

PMID- 9771724
TI  - No evidence for MUC 1-induced apoptosis.

PMID- 9771725
TI  - Inquiry into clinical trial scandal at Canadian research hospital.

PMID- 9771726
TI  - CRC alone in efforts to teach British doctors about cancer genetics.

PMID- 9771728
TI  - New research centers created worldwide.

PMID- 9771727
TI  - US panel recommends major tuberculosis vaccine effort.

PMID- 9771730
TI  - German professor resigns in protest at research obstruction.

PMID- 9771729
TI  - Skepticism surrounds Australia's biomedical research revolution.

PMID- 9771731
TI  - New funds for cancer research.

PMID- 9771732
TI  - Understanding the cell cycle.

PMID- 9771733
TI  - Cancer genetics, cytogenetics--defining the enemy within.

PMID- 9771734
TI  - Conformational changes: how small is big enough?

PMID- 9771735
TI  - GABA synapses enter the molecular big time.

PMID- 9771736
TI  - Forecasting brain storms.

PMID- 9771737
TI  - The fascinating life of hematopoietic stem cells.

PMID- 9771738
TI  - When smoke gets in your genes.

PMID- 9771739
TI  - Milking gene therapy.

PMID- 9771740
TI  - New clues to the emergence of flu pandemics.

PMID- 9771741
TI  - Lowered leptin slims immune response.

PMID- 9771742
TI  - Protein conformation dictates prion strain.

PMID- 9771743
TI  - Of calcium, caspases, and cognitive decline.

PMID- 9771744
TI  - Much IDO about pregnancy.

PMID- 9771745
TI  - Peroral gene therapy of lactose intolerance using an adeno-associated virus
      vector.
AB  - Gene therapy is usually reserved for severe and medically refractory disorders
      because of the toxicity, potential long-term risks and invasiveness of most gene
      transfer protocols. Here we show that an orally administered adeno-associated
      viral vector leads to persistent expression of a beta-galactosidase transgene in
      both gut epithelial and lamina propria cells, and that this approach results in
      long-term phenotypic recovery in an animal model of lactose intolerance. A gene
      'pill' associated with highly efficient and stable gene expression might be a
      practical and cost-effective strategy for even relatively mild disorders, such as
      lactase deficiency.

PMID- 9771746
TI  - In vivo selection of retrovirally transduced hematopoietic stem cells.
AB  - One of the main impediments to effective gene therapy of blood disorders is the
      resistance of human hematopoietic stem cells to stable genetic modification. We
      show here that a small minority of retrovirally transduced stem cells can be
      selectively enriched in vivo, which might be a way to circumvent this obstacle.
      We constructed two retroviral vectors containing an antifolate-resistant
      dihydrofolate reductase cDNA transcriptionally linked to a reporter gene. Mice
      were transplanted with transduced bone marrow cells and then treated with an
      antifolate-based regimen that kills unmodified stem cells. Drug treatment
      significantly increased the percentage of vector-expressing peripheral blood
      erythrocytes, platelets, granulocytes, and T and B lymphocytes. Secondary
      transplant experiments demonstrated that selection occurred at the level of
      hematopoietic stem cells. This system for in vivo stem-cell selection provides a
      means to increase the number of genetically modified cells after transplant, and
      may circumvent an substantial obstacle to successful gene therapy for human blood
      diseases.

PMID- 9771747
TI  - Gene mutations with characteristic deletions in cord blood T lymphocytes
      associated with passive maternal exposure to tobacco smoke.
AB  - We have investigated the molecular effects of passive maternal cigarette exposure
      in a newborn population and consider the possible implications of the observed
      genetic changes in the development of neoplastic diseases in children. We present
      a distribution analysis of somatic mutational events in a reporter gene, HPRT, in
      cord blood T lymphocytes from newborns after transplacental exposure to cigarette
      smoke. Analysis of 30 HPRT mutant isolates from 12 newborn infants born to
      mothers with no evidence of environmental exposure to cigarette smoke and 37 HPRT
      mutant isolates from 12 infants born to mothers exposed to passive cigarette
      smoke showed a significant difference in the HPRT mutational spectrum in those
      exposed in utero to cigarette smoke. The most notable change was an increase in
      'illegitimate' genomic deletions mediated by V(D)J recombinase, a recombination
      event associated with hematopoietic malignancies in early childhood. Recent
      epidemiological studies of maternal and paternal cigarette smoke exposure and
      childhood cancers may need to be re-interpreted, given these results.

PMID- 9771748
TI  - Leptin-independent hyperphagia and type 2 diabetes in mice with a mutated
      serotonin 5-HT2C receptor gene.
AB  - Brain serotonin and leptin signaling contribute substantially to the regulation
      of feeding and energy expenditure. Here we show that young adult mice with a
      targeted mutation of the serotonin 5-HT2C receptor gene consume more food despite
      normal responses to exogenous leptin administration. Chronic hyperphagia leads to
      a 'middle-aged'-onset obesity associated with a partial leptin resistance of late
      onset. In addition, older mice develop insulin resistance and impaired glucose
      tolerance. Mutant mice also responded more to high-fat feeding, leading to
      hyperglycemia without hyperlipidemia. These findings demonstrate a dissociation
      of serotonin and leptin signaling in the regulation of feeding and indicate that
      a perturbation of brain serotonin systems can predispose to type 2 diabetes.

PMID- 9771749
TI  - Eight prion strains have PrP(Sc) molecules with different conformations.
AB  - Variations in prions, which cause different incubation times and deposition
      patterns of the prion protein isoform called PrP(Sc), are often referred to as
      'strains'. We report here a highly sensitive, conformation-dependent immunoassay
      that discriminates PrP(Sc) molecules among eight different prion strains
      propagated in Syrian hamsters. This immunoassay quantifies PrP isoforms by
      simultaneously following antibody binding to the denatured and native forms of a
      protein. In a plot of the ratio of antibody binding to denatured/native PrP
      graphed as a function of the concentration of PrP(Sc), each strain occupies a
      unique position, indicative of a particular PrP(Sc) conformation. This conclusion
      is supported by a unique pattern of equilibrium unfolding of PrP(Sc) found with
      each strain. Our findings indicate that each of the eight prion strains has a
      PrP(Sc) molecule with a unique conformation and, in accordance with earlier
      results, indicate the biological properties of prion strains are 'enciphered' in
      the conformation of PrP(Sc) and that the variation in incubation times is related
      to the relative protease sensitivity of PrP(Sc) in each strain.

PMID- 9771750
TI  - Selective changes in single cell GABA(A) receptor subunit expression and function
      in temporal lobe epilepsy.
AB  - Temporal lobe epilepsy is the most prevalent seizure disorder in adults.
      Compromised inhibitory neurotransmitter function in the hippocampus contributes
      to the hyperexcitability generating this condition, but the underlying molecular
      mechanisms are unknown. Combining patch-clamp recording and single-cell mRNA
      amplification (aRNA) techniques in single dentate granule cells, we demonstrate
      that expression of GABA(A) receptor subunit mRNAs is substantially altered in
      neurons from epileptic rats. These changes in gene expression precede epilepsy
      onset by weeks and correlate with profound alterations in receptor function,
      indicating that aberrant GABA(A) receptor expression and function has an
      essential role in the process of epileptogenesis.

PMID- 9771751
TI  - Epileptic seizures can be anticipated by non-linear analysis.
AB  - Epileptic seizures are a principal brain dysfunction with important public health
      implications, as they affect 0.8% of humans. Many of these patients (20%) are
      resistant to treatment with drugs. The ability to anticipate the onset of
      seizures in such cases would permit clinical interventions. The view of chronic
      focal epilepsy now is that abnormally discharging neurons act as pacemakers to
      recruit and entrain other normal neurons by loss of inhibition and
      synchronization into a critical mass. Thus, preictal changes should be detectable
      during the stages of recruitment. Traditional signal analyses, such as the count
      of focal spike density, the frequency coherence or spectral analyses are not
      reliable predictors. Non-linear indicators may undergo consistent changes around
      seizure onset. Our objective was to follow the transition into seizure by
      reconstructing intracranial recordings in implanted patients as trajectories in a
      phase space and then introduce non-linear indicators to characterize them. These
      indicators take into account the extended spatio-temporal nature of the epileptic
      recruitment processes and the corresponding physiological events governed by
      short-term causalities in the time series. We demonstrate that in most cases (17
      of 19), seizure onset could be anticipated well in advance (between 2-6 minutes
      beforehand), and that all subjects seemed to share a similar 'route' towards
      seizure.

PMID- 9771752
TI  - Calsenilin: a calcium-binding protein that interacts with the presenilins and
      regulates the levels of a presenilin fragment.
AB  - Most early-onset familial Alzheimer disease (AD) cases are caused by mutations in
      the highly related genes presenilin 1 (PS1) and presenilin 2 (PS2). Presenilin
      mutations produce increases in beta-amyloid (Abeta) formation and apoptosis in
      many experimental systems. A cDNA (ALG-3) encoding the last 103 amino acids of
      PS2 has been identified as a potent inhibitor of apoptosis. Using this PS2 domain
      in the yeast two-hybrid system, we have identified a neuronal protein that binds
      calcium and presenilin, which we call calsenilin. Calsenilin interacts with both
      PS1 and PS2 in cultured cells, and can regulate the levels of a proteolytic
      product of PS2. Thus, calsenilin may mediate the effects of wild-type and mutant
      presenilins on apoptosis and on Abeta formation. Further characterization of
      calsenilin may lead to an understanding of the normal role of the presenilins and
      of the role of the presenilins in Alzheimer disease.

PMID- 9771754
TI  - Selective repopulation of normal mouse liver by Fas/CD95-resistant hepatocytes.
AB  - Hepatocyte transplantation might represent a potential therapeutic alternative to
      liver transplantation in the future; however, transplanted cells have a limited
      capacity to repopulate the liver, as they do not proliferate under normal
      conditions. Recently, studies in urokinase (uPA) transgenic mice and in
      fumarylacetoacetate hydrolase (FAH)-deficient mice have shown that the liver can
      be repopulated by genetically engineered hepatocytes harboring a selective
      advantage over resident hepatocytes. We have reported that transgenic mice
      expressing human Bcl-2 in their hepatocytes are protected from Fas/CD95-mediated
      liver apoptosis. We now show that Bcl-2 transplanted hepatocytes selectively
      repopulate the liver of mice treated with nonlethal doses of the anti-Fas
      antibody Jo2. FK 506 immunosuppressed mice were transplanted by splenic injection
      with Bcl-2 hepatocytes. The livers of female recipients were repopulated by male
      Bcl-2 transgenic hepatocytes, as much as 16%, after 8 to 12 administrations of
      Jo2. This only occurred after anti-Fas treatment, confirming that resistance to
      Fas-induced apoptosis constituted the selective advantage of these transplanted
      hepatocytes. Thus, we have demonstrated a method for increasing genetic
      reconstitution of the liver through selective repopulation with modified
      transgenic hepatocytes, which will allow optimization of cell and gene therapy in
      the liver.

PMID- 9771753
TI  - HIV-infected subjects with the E4 allele for APOE have excess dementia and
      peripheral neuropathy.
AB  - HIV produces a chronic viral infection of the central nervous system that elicits
      chronic glial activation and overexpression of glial cytokines that are also
      implicated in Alzheimer disease (AD) pathogenesis. A genetic risk factor for AD
      is the E4 isoform for apolipoprotein E (APOE). Here we compare the frequency of
      neurologic symptoms for subjects with and without the E4 isoform (E4(+)and E4(-),
      respectively) in an HIV cohort. Compared with E4(-) subjects, twice as many E4(+)
      subjects were demented (30% compared with 15%) or had peripheral neuropathy (70%
      compared with 39%) at least once, and they had threefold more symptomatic
      examinations (13% compared with 3% and 42% compared with 14%, respectively)(P <
      0.0001). Thus, neurologic symptoms for HIV-infection and AD are linked through an
      etiologic risk factor. Long-term survivors of HIV infection with E4 may be at
      high risk for AD; conversely, gene-viral interactions may speed AD pathogenesis.

PMID- 9771755
TI  - Vitamin E suppresses isoprostane generation in vivo and reduces atherosclerosis
      in ApoE-deficient mice.
AB  - Oxidative modification of low density lipoprotein (LDL) has been implicated in
      atherogenesis. Evidence consistent with this hypothesis includes the presence of
      oxidized lipids in atherosclerotic lesions, the newly discovered biological
      properties conferred on LDL by oxidation and the acceleration of atherogenesis by
      in vivo delivery of the gene for 15-lipoxygenase, an oxidizing enzyme present in
      atherosclerotic lesions. However, it is still unknown whether oxidative stress
      actually coincides with the evolution of the disease or whether it is of
      functional relevance to atherogenesis in vivo. Isoprostanes are products of
      arachidonic acid catalyzed by free radicals, which reflect oxidative stress and
      lipid peroxidation in vivo. Elevation of tissue and urinary isoprostanes is
      characteristic of human atherosclerosis. Here, deficiency in apolipoprotein E in
      the mouse (apoE-/-) resulted in atherogenesis and an increase in iPF2alpha-VI, an
      F2-isoprostane, in urine, plasma and vascular tissue. Supplementation with
      vitamin E significantly reduced isoprostane generation, but had no effect on
      plasma cholesterol levels in apoE-/- mice. Aortic lesion areas and iPF2alpha-VI
      levels in the arterial wall were also reduced significantly by vitamin E. Our
      results indicate that oxidative stress is increased in the apoE-/- mouse, is of
      functional importance in the evolution of atherosclerosis and can be suppressed
      by oral administration of vitamin E.

PMID- 9771756
TI  - Vaccine-induced cytotoxic T lymphocytes protect against retroviral challenge.
AB  - The development of prophylactic vaccines against retroviral diseases has been
      impeded by the lack of obvious immune correlates for protection. Cytotoxic T
      lymphocyte (CTL), CD4-lymphocyteS, chemokine and/or antibody responses have all
      been associated with protection against HIV and AIDS; however, effective and safe
      vaccination strategies remain elusive. Here we show that vaccination with a
      minimal ovine CTL peptide epitope identified within gp51 of the retrovirus bovine
      leukemia virus (BLV), consistently induced peptide-specific CTLs. Only sheep
      whose CTLs were also capable of recognizing retrovirus-infected cells were fully
      protected when challenged with BLV. This retrovirus displays limited sequence
      variation; thus, in the relative absence of confounding CTL escape variants,
      virus-specific CTLs targeting a single epitope were able to prevent the
      establishment of a latent retroviral infection.

PMID- 9771758
TI  - Ion channels and neurological disease: DNA based diagnosis is now possible, and
      ion channels may be important in common paroxysmal disorders.

PMID- 9771757
TI  - Use of the green fluorescent protein as a marker to identify and track
      genetically modified hematopoietic cells.

PMID- 9771759
TI  - Schizophrenia neuropathology: tortoises and hares.

PMID- 9771760
TI  - Quality of life in multiple sclerosis.

PMID- 9771761
TI  - Re-emergence of surgery for dystonia.

PMID- 9771762
TI  - Crime in Huntington's disease.

PMID- 9771764
TI  - Reduced dendritic spine density on cerebral cortical pyramidal neurons in
      schizophrenia.
AB  - OBJECTIVE: A pilot study of the density of dendritic spines on pyramidal neurons
      in layer III of human temporal and frontal cerebral neocortex in schizophrenia.
      METHODS: Postmortem material from a group of eight prospectively diagnosed
      schizophrenic patients, five archive schizophrenic patients, 11 non-schizophrenic
      controls, and one patient with schizophrenia-like psychosis, thought to be due to
      substance misuse, was impregnated with a rapid Golgi method. Spines were counted
      on the dendrites of pyramidal neurons in temporal and frontal association areas,
      of which the soma was in layer III (which take part in corticocortical
      connectivity) and which met strict criteria for impregnation quality. Altogether
      25 blocks were studied in the schizophrenic group and 21 in the controls. If more
      than one block was examined from a single area, the counts for that area were
      averaged. All measurements were made blind: diagnoses were only disclosed by a
      third party after measurements were completed. Possible confounding affects of
      coexisting Alzheimer's disease were taken into account, as were the effects of
      age at death and postmortem interval. RESULTS: There was a significant (p<0.001)
      reduction in the numerical density of spines in schizophrenia (276/mm in control
      temporal cortex and 112/mm in schizophrenic patients, and 299 and 101
      respectively in the frontal cortex). An analysis of variance, taking out effects
      of age at death and postmortem interval, which might have explained the low spine
      density for some of the schizophrenic patients, did not affect the significance
      of the results. CONCLUSION: The results support the concept of there being a
      defect in the fine structure of dendrites of pyramidal neurons, involving loss of
      spines, in schizophrenia and may help to explain the loss of cortical volume
      without loss of neurons in this condition, although the effect of neuroleptic
      drugs cannot be ruled out.

PMID- 9771765
TI  - Cue dependent right hemineglect in schizophrenia: a kinematic analysis.
AB  - OBJECTIVES: Schizophrenia may result from disturbed attentional processes and/or
      defective internal cueing. Attention for subsequent action within a cued movement
      task was therefore studied, testing specific hypotheses of hemispheric
      dysfunction and of impaired interhemispheric communication. METHOD: Fifteen
      patients with schizophrenia and 15 matched controls were either cued or uncued
      when moving a pen to a target on their right or left side with their right or
      left hand. Pen tip position was sampled at 200 Hz on a WACOM SD420 graphics
      tablet for subsequent kinematic analysis. RESULTS: Patients with schizophrenia
      were slower initiating rightwards movements without a cue. Patients also
      exhibited reduced abductive/adductive differences in the shape of their movement
      trajectories, implying differences in interhemispheric communication.
      CONCLUSIONS: It is speculated that schizophrenia is a form of cue dependent right
      hemineglect.

PMID- 9771763
TI  - Dystonia and chorea in acquired systemic disorders.
AB  - Dystonia and chorea are uncommon accompaniments, but sometimes the presenting
      features of certain acquired systemic disorders that presumably alter basal
      ganglia function. Hypoxia-ischaemia may injure the basal ganglia through
      hypoperfusion of subcortical vascular watershed regions and by altering striatal
      neurotransmitter systems. Toxins interfere with striatal mitochondrial function,
      resulting in cellular hypoxia. Infections may affect the basal ganglia by causing
      vasculitic ischaemia, through the development of antibodies to basal ganglia
      epitopes, by direct invasion of the basal ganglia by the organism, or through
      cytotoxins causing neuronal injury. Autoimmune disorders alter striatal function
      by causing a vasculopathy, by direct reaction of antibodies with basal ganglia
      epitopes, or by stimulating the generation of a cytotoxic or inflammatory
      reaction. Endocrine and electrolyte abnormalities influence neurotransmitter
      balance or affect ion channel function and signalling in the basal ganglia. In
      general, the production of chorea involves dysfunction of the indirect pathway
      from the caudate and putamen to the internal globus pallidus, whereas dystonia is
      generated by dysfunction of the direct pathway. The time of the onset of the
      movement disorder relative to the primary disease process, and course vary with
      the age of the patient and the underlying pathology. Treatment of dystonia or
      chorea associated with a systemic medical disorder must initially consider the
      systemic disorder.

PMID- 9771766
TI  - Quality of life in multiple sclerosis in France, Germany, and the United Kingdom.
      Cost of Multiple Sclerosis Study Group.
AB  - OBJECTIVE: To assess the quality of life (QoL) of patients with multiple
      sclerosis in France, Germany, and the United Kingdom with a cross sectional
      study. METHODS: Patients were classified into three severity groups according to
      the expanded disability severity scale (EDSS); stage I, II, and III,
      corresponding to mild (EDSS 1.0-3.5), moderate (EDSS 4.0-6.0), or severe (EDSS
      6.5-8.0) multiple sclerosis respectively. Ninety patients with multiple sclerosis
      and 30 control patients without multiple sclerosis were recruited in each
      country. Control patients were matched to the patients with multiple sclerosis
      according to age and sex. Quality of life was assessed using the functional
      status questionnaire (FSQ). RESULTS: The aspects of QoL that were mostly affected
      in the three countries under study were physical function and general wellbeing.
      Social role function decreased with increased severity of disease in France and
      in particular in Germany. Multiple sclerosis did not seem to have an impact on
      psychological function. The QoL of control patients was systematically higher
      than that of patients with multiple sclerosis. CONCLUSIONS: Use of such a generic
      scale showed that progression of multiple sclerosis is accompanied by a decrease
      in QoL and suggested that this could be a relevant measurement in assessing the
      effect of treatment and progression of disease. Variation between countries,
      however, may be important.

PMID- 9771767
TI  - Crime in Huntington's disease: a study of registered offences among patients,
      relatives, and controls.
AB  - OBJECTIVES: Criminal behaviour has been described as a problem in Huntington's
      disease, but systematic studies including control groups have been missing. Based
      on information from Danish registries, rates and types of crime committed by
      patients with Huntington's disease, non-affected relatives, and controls were
      studied. METHODS: 99 males and 151 females with Huntington's disease were
      compared with 334 non-affected first degree relatives (134 men and 200 women) and
      to matched control groups as to frequencies and types of registered criminal
      convictions. Due to specific age criteria, the group of relatives comprised only
      about 9% carriers of the gene coding for Huntington's disease. RESULTS: In male
      patients, crime rates were significantly increased compared with first degree
      relatives (RR=2.8) and controls (RR=2.3). All types of crime occurred more often
      in male patients; more severe crimes (murder, rape, arson) were not reported.
      Rates of drunken driving were significantly increased compared with relatives
      (RR=3.8) and controls (RR=7.1). Crime rates were neither increased in female
      patients nor in male and female first degree relatives. CONCLUSION: The results
      indicate increased prevalence of criminal behaviour in males carrying the gene
      for Huntington's disease. The crimes committed seem to be of relatively minor
      severity and are probably closely linked to the personality changes often seen as
      a result of the disease process, although depressive reactions to the disease,
      with secondary alcohol misuse, may also play a part. Environmental and familial
      factors shared by patients and non-affected at risk persons seem to be of less
      aetiological importance.

PMID- 9771768
TI  - Outcome of selective ramisectomy for botulinum toxin resistant torticollis.
AB  - OBJECTIVE: To investigate the long term outcome of selective ramisectomy
      denervation in patients with botulinum toxin resistant spasmodic torticollis.
      BACKGROUND: The published surgical series of ramisectomy treatment for
      torticollis do not provide systematic information on patients who develop
      resistance to the current standard of treatment-botulium toxin injections.
      Moreover, there is little information on surgical outcome using rating scale
      measurements of torticollis, or assessments of functional and occupational
      capacity. METHODS: Using a structured interview format and videotape assessments
      of severity of dystonia in a retrospective fashion, detailed follow up
      information was obtained on 16 patients who underwent open label selective
      denervation for severe, disabling torticollis, refractory to injections of
      botulinum toxin. RESULTS: Of 16 patients with disabling torticollis followed up
      postoperatively for a mean of 5 years, six (37.5%) had a moderate or complete
      return of normal neck function, as determined using functional capacity scales,
      whereas 10 had only minimal relief of dystonia or gain in function. Six of the 16
      patients (37.5%) underwent a second peripheral denervation operation, and one
      required a third. Of 11 patients working outside the home before surgery, nine
      were disabled by dystonia, and only one continued to work after surgery. Dystonia
      rating scale scores of videotaped examinations using a modification of the
      Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) improved in 12 of 14
      patients (85.7%) who underwent selective ramisectomy. When patients with primary
      botulinum toxin resistance were excluded, the magnitude of benefit for this
      subgroup was 31.9% of the baseline dystonia score (p<0.0002), comparable with the
      degree of improvement in a group of control patients receiving botulinum toxin
      treatment for torticollis. CONCLUSION: About one third of patients with
      torticollis resistant to injections of botulinum toxin may derive modest long
      term functional improvement from selective denervation, with a reduction in
      dystonia by about 30%, but remain unable to work.

PMID- 9771769
TI  - The effect of unilateral posteroventral pallidotomy on the kinematics of the
      reach to grasp movement.
AB  - OBJECTIVE: To assess postoperative effects of unilateral posteroventral
      pallidotomy on the organisation of upper limb movement. METHODS: A three
      dimensional kinematic system (ELITE, B/T/S/ Italy) was used to record reach to
      grasp movements to objects of either small (0.7 cm) or large (8 cm) diameter
      placed at a reaching distance of either 20 or 30 cm. Four patients with
      Parkinson's disease were assessed in "off" (12 hours without medication) and "on"
      (1 hour after administration of medication) preoperatively and postoperatively.
      RESULTS: Duration of the movement and the time spent in arm deceleration were
      significantly reduced after surgery. However, movement patterning according to
      object size was adversely affected. Postoperatively, all four patients showed an
      abnormal pattern of a longer movement duration, and three showed a longer time of
      reaching arm deceleration, for reach to grasp movements to the large object than
      for those to the small object. CONCLUSION: Posteroventral pallidotomy seems to be
      beneficial in reducing bradykinesia of upper limb movements but may have "costs"
      to movement patterning, particularly for reach to grasp movements to objects of
      differing sizes. This study raises interesting questions about the role of the
      globus pallidus interna in coordinating stimulus bound visual information with
      appropriate motor patterning.

PMID- 9771771
TI  - Myasthenia gravis: a population based epidemiological study in Cambridgeshire,
      England.
AB  - OBJECTIVES: To perform a comprehensive survey of myasthenia gravis in the county
      of Cambridgeshire, England, establishing contemporary epidemiological data.
      METHODS: Cases were ascertained from multiple sources. Prevalent patients were
      visited and assessed by means of a standardised questionnaire and examination
      complemented by review of medical case notes. RESULTS: One hundred cases were
      identified in a population of 684000 (prevalence 15 per 100000 population, 95%
      confidence intervals (95% CIs) 12-18). Thirty eight new diagnoses were made over
      a five year period providing an incidence of 1.1/100000 population/year. The sex
      ratio was 2:1 F:M. After a mean follow up of 11.7 years, symptomatic disease was
      still restricted to ocular muscles in 25 patients. Thirty four of 100 patients
      underwent thymectomy a mean of 0.8 years after presentation, and a thymoma was
      present in 12. Highest remission rates were seen in patients presenting with
      generalised disease who underwent thymectomy but did not have a thymoma (27%).
      Cosegregation of an additional autoimmune disease occurred in 27 patients and in
      24/49 (49%) women with onset<50 years of age. CONCLUSIONS: This, the second
      highest reported prevalence for myasthenia, is likely to be the result of optimum
      case ascertainment, increased disease duration, application of complex diagnostic
      tests, and the impact of an aging population leading to a relative increase in
      the prevalence of ocular myasthenia.

PMID- 9771770
TI  - Spinal corpora amylacea and motor neuron disease: a quantitative study.
AB  - OBJECTIVE: To test the hypothesis that as there is growing evidence that corpora
      amylacea, or amyloid bodies, in the CNS are derived primarily from neurons, it
      might be expected that their numbers in the spinal cord would decline with loss
      of neurons in motor neuron degeneration as they do in the retina on destruction
      of ganglion cells by glaucoma. METHODS: The numbers of corpora amylacea were
      counted in PAS stained transverse sections of the lumbar cord from 27 patients
      with motor neuron disease and 21 control subjects of similar age and sex mix. The
      numbers and sizes of corpora amylacea were determined both in the anterior horn
      grey matter and in the submeningeal white matter regions in each case. RESULTS:
      In both groups the total numbers in the white matter and submeningeal regions
      ranged from 160 to more than 5000/section and there was minimal significant
      difference between the two groups. No relation with age was found in this narrow
      age range. The mean diameters of the corpora amylacea were significantly less in
      the grey matter of both groups than in the submeningeal regions. However, their
      densities in the grey matter of the anterior horn were significantly reduced in
      the spinal cord sections in the motor neuron disease group, but only where few
      motor neurons remained. CONCLUSIONS: These findings support the view that corpora
      amylacea may arise from neurons, and suggest that that there may be two
      compartments, one mobile and one static, the second most likely remaining in the
      periphery of the spinal cord for prolonged periods.

PMID- 9771772
TI  - Effects of transient and persistent cerebrospinal fluid drainage on sleep
      disordered breathing in patients with idiopathic adult hydrocephalus syndrome.
AB  - OBJECTIVES: To examine sleep disordered breathing including obstructive sleep
      apnoea in patients with idiopathic adult hydrocephalus syndrome (IAHS) and to
      study the effects of CSF drainage and shunting procedure on sleep disordered
      breathing. METHODS: In 17 patients with IAHS polysomnographic investigations were
      performed before and after lumbar CSF drainage and after shunt operation.
      RESULTS: Baseline investigations documented a high prevalence of sleep related
      obstructive respiratory events (respiratory disturbance index >10 in 65% of the
      patients) and impaired sleep structure. There was no correlation between
      respiratory disturbance index and CSF pressure. Minimum oxygen saturation was
      highly correlated with cognitive function. Neither lumbar CSF drainage nor
      shunting alleviated the respiratory disturbance index. REM and delta sleep
      increased initially after shunting but there was no sustained effect on sleep
      quality. CONCLUSIONS: Sleep disordered breathing is a prevalent finding in
      patients with IAHS. The shortcoming of CSF drainage to improve sleep disordered
      breathing either transiently or permanently implies that sleep disordered
      breathing is a coexistent condition, or an irreversible consequence of the
      hydrocephalus, with a potential of causing additional dysfunction in IAHS.

PMID- 9771775
TI  - Pneumatic drill through the foramen magnum.

PMID- 9771773
TI  - The hormonal response to stress is not modified by the dramatic decrease in
      prolactin plasma concentration during surgery for microprolactinoma.
AB  - OBJECTIVES: To determine the endocrine response to surgical stress in a
      homogeneous population of 36 women with microprolactinomas, particularly to
      evaluate the effect of the sharp decrease in plasma prolactin on stress induced
      hormonal secretion. In addition, the effects of exogenous opiates on prolactin
      secretion were studied. METHODS: The plasma kinetics of cortisol, prolactin,
      ACTH, GH, and beta-endorphin like immunoreactivity (beta-ELI) were analysed by
      including patients operated on with strict anaesthetic and surgical protocols,
      and by sampling blood every 10 minutes, starting at premedication up to 3 hours
      after induction. RESULTS AND CONCLUSIONS: (a) Surgical stress or opiate
      administration did not induce prolactin release in patients with
      microprolactinoma. (b) The dramatic decrease in prolactin concentrations have
      apparently no effect on the release of other hormones involved in stress. (c) The
      existence of an early GH peak, independently of any surgical procedure, strongly
      suggests that GH is released by surgical stress whereas beta-endorphin is
      secreted in response to pain. Thus GH may be a useful marker of surgical stress.

PMID- 9771774
TI  - Inherited prothrombotic states and ischaemic stroke in childhood.
AB  - OBJECTIVE: To investigate the prevalence of currently recognised inherited
      prothrombotic states in a population of children with arterial stroke. METHODS:
      Children with arterial stroke presenting to a tertiary level paediatric neurology
      centre between 1990 and 1996 were investigated for inherited prothrombotic
      states. RESULTS: Sixty seven children with arterial stroke were investigated.
      Abnormalities were initially identified in 16 patients; however, only eight
      children (12%) had an inherited prothrombotic state. This was type 1 protein S
      deficiency in one patient, the factor V Leiden mutation in six, and activated
      protein C resistance (without the factor V Leiden mutation) in one. The
      prevalence of the factor V Leiden mutation was not significantly higher in
      children with arterial stroke (12%) than in a control population of children
      without thrombosis attending the same institution (5.2%; Fisher's exact test,
      p=0.19; difference in prevalence between patients and controls (95% confidence
      interval)=6.8% (-2.78% to 16.8%)). CONCLUSIONS: Currently recognised inherited
      prothrombotic tendencies were rarely associated with stroke in this group of
      children, although larger numbers of patients would be needed to confirm this.
      Age appropriate normal values should be used when interpreting the results of a
      prothrombotic screen. Prothrombotic abnormalities seen acutely are as often
      transient as inherited. Longitudinal assessment and family studies are required
      before low concentrations of an anticoagulant protein found acutely can be
      attributed to an inherited abnormality.

PMID- 9771777
TI  - Reduction in temporal N-acetylaspartate and creatine (or choline) ratio in
      temporal lobe epilepsy: does this 1H-magnetic resonance spectroscopy finding mean
      poor seizure control?
AB  - BACKGROUND: Proton magnetic resonance spectroscopy (1H-MRS) is a potentially
      useful tool in the in vivo investigation of brain metabolites in intractable
      temporal lobe epilepsy (TLE). Focal N-acetylaspartate (NAA) reductions have been
      correlated with mesial temporal sclerosis (MTS) in surgically resected
      epileptogenic foci. OBJECTIVE: To evaluate the abnormalities in the metabolites
      NAA, creatine+ phosphocreatine (Cr), and choline containing compounds (Cho) in
      the temporal lobe of medically refractory patients with temporal lobe epilepsy,
      seizure free patients with temporal lobe epilepsy, and normal controls. PATIENTS
      AND METHODS: Ten refractory patients, 12 seizure free patients with temporal lobe
      epilepsy, and 10 age matched normal controls were studied by 1H-magnetic
      resonance spectroscopy. All patients had consistently unilateral temporal EEG
      abnormalities and a normal brain MRI. Proton MR spectra were obtained from an 8
      ml volume in the medial temporal lobes in patients with temporal lobe epilepsy
      (ipsilateral to EEG foci) and the normal controls. The signals measured were
      expressed in terms of NAA/Cr, NAA/Cho, and Cho/Cr. RESULTS: When compared with
      seizure free patients with temporal lobe epilepsy and normal controls, the 10
      refractory patients with temporal lobe epilepsy had a lower mean (SEM) NAA/Cr
      ratio (1.65 (0.53) v 2.62 (0.60), and 2.66 (0.73); p<0.002 and p<0.006) and a
      lower mean NAA/Cho ratio (1.59 (0.79) v 2.83 (1.33) and 2.58 (0.67); p<0.02 and
      p<0.007). Furthermore, the two patients showing the lowest NAA/Cr ratios (1.47
      and 1.73) in the seizure free group had had a past period of poor seizure
      control. CONCLUSIONS: There were reduced temporal NAA/Cr and NAA/Cho ratios,
      suggesting neuronal loss or damage, associated with past or present poor seizure
      control in the patients with temporal lobe epilepsy, but it does not exclude the
      possibility of a future complete seizure control (seizure free patients with
      temporal lobe epilepsy at the time of 1H-MRS). This study warrants further 1H-MRS
      investigation with a larger series of patients with temporal lobe epilepsy.

PMID- 9771776
TI  - MELAS: a new disease associated mitochondrial DNA mutation and evidence for
      further genetic heterogeneity.
AB  - OBJECTIVES: To define the molecular genetic basis of the MELAS phenotype in five
      patients without any known mutation of mitochondrial DNA. METHODS: Systematic
      automated mitochondrial DNA sequencing of all mitochondrial transfer RNA and
      cytochrome c oxidase genes was undertaken in five patients who had the MELAS
      phenotype. RESULTS: A novel heteroplasmic mitochondrial DNA mutation was
      identified in the transfer RNA gene for phenylalanine in one case (patient 3).
      This mutation was not detected in the patient's blood or in her mother's blood.
      No pathogenic mutations were identified in the other four patients. CONCLUSIONS:
      This is the first point mutation in the transfer RNA gene for phenylalanine to be
      associated with MELAS. The absence of mutations in the remaining four patients
      suggests that there is further genetic heterogeneity associated with this
      mitochondrial phenotype.

PMID- 9771778
TI  - Tinnitus after head injury: evidence from otoacoustic emissions.
AB  - OBJECTIVE: Tinnitus may be caused by a lesion or dysfunction at any level of the
      auditory system. This study explores cochlear mechanics using otoacoustic
      emissions in patients with tinnitus after head injury, in whom there seems to be
      evidence to support dysfunction within the CNS. METHODS: The study included 20
      patients with tinnitus and other auditory symptoms, such as hyperacusis and
      difficulty in listening in background noise, after head injury, in the presence
      of an "intact" auditory periphery (normal or near normal audiometric thresholds).
      They were compared with 20 normal subjects and 12 subjects with head injury, but
      without tinnitus, who had similar audiometric thresholds. In all subjects
      otoacoustic emissions, including transient click-evoked (TEOAEs) and spontaneous
      otoacoustic emissions (SOAEs), were recorded, and a test of efferent medial
      olivocochlear suppression, consisting of recording of TEOAEs under contralateral
      stimulation, was performed. RESULTS: A significantly higher prevalence of SOAEs
      (100%), higher TEOAE response amplitudes, and reduced medial olivocochlear
      suppression in patients with tinnitus in comparison with subjects without
      tinnitus have been found. CONCLUSION: These findings have been interpreted to be
      an extracochlear phenomenon, in which the reduction in central efferent
      suppression of cochlear mechanics, leading to an increase in cochlear amplifier
      gain, was subsequent to head injury. Auditory symptoms in these patients seemed
      to constitute the "disinhibition syndrome".

PMID- 9771779
TI  - Electrophysiological features of central motor conduction in spinocerebellar
      atrophy type 1, type 2, and Machado-Joseph disease.
AB  - OBJECTIVES: To characterise electrophysiologically the central motor conduction
      of spinocerebellar atrophy type 1 (SCA1), type 2 (SCA2), and Machado-Joseph
      disease (MJD). METHODS: Motor evoked potentials (MEPs) triggered by transcranial
      magnetic stimulation (TMS) was used to investigate the functions of corticospinal
      tracts of 10 patients with SCA1, 10 with MJD, and eight with SCA2 in addition to
      pathological study of the spinal cord in a patient with SCA1. RESULTS: Central
      motor conduction time (CMCT) was extremely prolonged and the MEP threshold
      increased in all patients with SCA1, whereas both were normal in patients with
      SCA2 or MJD. The MEP size in MJD was larger than normal, but was normal in SCA1
      and SCA2. A pathological investigation of the corticospinal tract of the spinal
      cord of a patient with SCA1 showed selective loss of large diameter fibres.
      CONCLUSIONS: SCA1, SCA2, and MJD differ in their pathophysiological features of
      the central motor tract and can be differentiated from each other by MEP values
      for the lower limb muscles, even though their neurological symptoms are sometimes
      similar.

PMID- 9771780
TI  - The diagnostic sensitivity of different F wave parameters.
AB  - OBJECTIVE: To examine the relative diagnostic sensitivity of various F wave
      parameters. METHODS: Normal values for minimum, mean, and maximum F wave latency,
      chronodispersion, and persistence in the four major motor nerves were established
      and systematically applied to at least four separate categories of patients
      (radiculopathies, polyneuropathies, mononeuropathies, and others). F Waves were
      studied both isolated and in comparison with other motor nerve conduction
      parameters. RESULTS: F Chronodispersion was the most often abnormal parameter,
      particularly in lumbosacral radiculopathies. Minimum F wave latency was more
      useful in polyneuropathies. Compared with minimum F wave latency, F
      chronodispersion was able to identify most additional cases. CONCLUSIONS: F Wave
      studies should include minimum F wave latency and chronodispersion.

PMID- 9771781
TI  - Effects of exercise on cognitive and motor function in chronic fatigue syndrome
      and depression.
AB  - OBJECTIVES: Patients with chronic fatigue syndrome complain of physical and
      mental fatigue that is worsened by exertion. It was predicted that the cognitive
      and motor responses to vigorous exercise in patients with chronic fatigue
      syndrome would differ from those in depressed and healthy controls. METHODS: Ten
      patients with chronic fatigue syndrome, 10 with depressive illness, and 10
      healthy controls completed cognitive and muscle strength testing before and after
      a treadmill exercise test. Measures of cardiovascular functioning and perceived
      effort, fatigue, and mood were taken during each stage of testing. RESULTS:
      Depressed patients performed worst on cognitive tests at baseline. During the
      treadmill test, patients with chronic fatigue syndrome had higher ratings of
      perceived effort and fatigue than both control groups, whereas patients with
      depression reported lower mood. After exertion, patients with chronic fatigue
      syndrome showed a greater decrease than healthy controls on everyday tests of
      focused (p=0.02) and sustained (p=0.001) attention, as well as greater
      deterioration than depressed patients on the focused attention task (p=0.03). No
      between group differences were found in cardiovascular or symptom measures taken
      during the cognitive testing. CONCLUSIONS: Patients with chronic fatigue syndrome
      show a specific sensitivity to the effects of exertion on effortful cognitive
      functioning. This occurs despite subjective and objective evidence of effort
      allocation in chronic fatigue syndrome, suggesting that patients have reduced
      working memory capacity, or a greater demand to monitor cognitive processes, or
      both. Further insight into the pathophysiology of the core complaints in chronic
      fatigue syndrome is likely to be realised by studying the effects of exercise on
      other aspects of everyday functioning.

PMID- 9771783
TI  - Ivan Mikhailovich Sechenov (1829-1905).

PMID- 9771782
TI  - Significance of factors contributing to surgical complications and to late
      outcome after elective surgery of cerebral arteriovenous malformations.
AB  - OBJECTIVES: This study focuses on the relevance of size, eloquence, type of
      venous drainage, the Spetzler-Martin scale as a whole, and other factors, such as
      rupture of cerebral arteriovenous malformations (AVMs) for the prediction of
      neurological deficits in the context of microsurgical AVM removal. METHODS: One
      hundred and fifty patients with AVMs, whose data were retrieved from a
      prospectively employed computerised data bank were included. Seventeen patients
      (11.3%) underwent preoperative embolisation. According to the Spetzler-Martin
      scale they were graded as follows: 22.0% grade I, 32.0% grade II, 29.3% grade
      III, 14.0% grade IV, and 2.7% grade V. Intracerebral haemorrhage was present in
      39.0%. The AVMs were <3 cm in 52.00/0, 3-6 cm in 43.3% and >6 cm in 4.7%; 59.3%
      of the AVMs were eloquently located and 29.3% had deep venous drainage (DVD).
      Follow up information was assessed 6 months after surgery in all but one patient,
      who died. The applied statistical test was chi2. RESULTS: Surgical morbidity was
      15.3%. Early new deficits were noted in 39.3%, permanent new deficits in 10.6%,
      being significant (major) in 7.3%. The occurrence of permanent deficits
      correlated significantly with size, deep venous drainage, and the Spetzler-Martin
      scale. There was statistical evidence for a trend in risk of poor surgical
      outcome across the three categories non-eloquent, "less eloquent" (for example,
      visual cortex) and "highly eloquent" (brainstem, basal ganglia, or precentral
      cortex) with the last being associated with the highest risk for permanent
      neurological compromise. CONCLUSION: "Eloquence" of the Spetzler-Martin scale
      should be divided into "highly eloquent" and "less eloquent", which is important
      for risk analysis of the treatment of asymptomatic and deep seated AVMs and for
      future trials comparing various treatment modalities. In addition, resection of
      eloquent AVMs v non-eloquent ones is significantly associated with higher
      surgical morbidity.

PMID- 9771785
TI  - Vasomotor reactivity is exhausted in transient ischaemic attacks with limb
      shaking.
AB  - OBJECTIVES: To investigate cerebral vasomotor reactivity in five patients with
      limb shaking transient ischaemic attacks by using transcranial Doppler
      sonography. METHOD: Attacks with transient limb shaking were unilateral in four
      patients and bilateral in one. Internal carotid arteries on the side opposite the
      abnormal limb movements showed three 90-95% stenoses and three occlusions as
      assessed by cerebral angiography in three and magnetic resonance angiography and
      ultrasound in one case each. Reactivity of cerebral resistance vessels was
      studied by measuring peak mean velocities in the middle cerebral artery (MCA)
      before and after the application of CO2 enriched air. Reference values were
      obtained from 25 normal subjects. RESULTS: During hypercapnia peak mean
      velocities slightly decreased in five MCAs (steal phenomenon) and remained
      unchanged in one MCA opposite the abnormal movements, whereas the other MCAs
      showed normal reactivities. CONCLUSION: The delineation of an exhausted cerebral
      vasoreactivity in all hemispheres opposite the involuntary limb movements
      suggests that haemodynamic failure is the cause of transient ischaemic attacks
      with limb shaking.

PMID- 9771784
TI  - Autism and visual agnosia in a child with right occipital lobectomy.
AB  - OBJECTIVES: Autistic disorder is a developmental handicap with an unknown
      neurological basis. Current neuropsychological models for autism suggest an
      abnormal construction of visual perceptual representation or a deficit in
      executive functions. These models predict cerebral lesions in the temporo
      occipital or frontal regions of autistic patients. The present study aimed at
      studying the presence of symptoms of autism and visual agnosia in a 13 year old
      girl who had a right temporo-occipital cortical dysplasia that was surgically
      removed at the age of 7. METHODS: Neuropsychological evaluation included Wechsler
      and Kaufman intelligence scales, a test of word fluency, digit span, Corsi block,
      California verbal learning, Trail making, Benton facial recognition, Snoodgrass
      object recognition tests, Rivermead face learning subtest, and developmental test
      of visual perception. The ADI-R was used to show current and retrospective
      diagnosis of autistic disorder. Neuroimagery included brain MRI, single photon
      emission computed tomography (SPECT), and PET. RESULTS: Brain MRI showed a right
      occipital defect and an abnormal hyperintensity of the right temporal cortex. PET
      and SPECT disclosed a left frontal hypometabolism together with the right
      occipital defect. Neuropsychological testing showed a visual apperceptive agnosia
      and executive function deficits. Psychiatric study confirmed the diagnosis of
      autistic disorder. CONCLUSIONS: Although the possibility that autism and visual
      agnosia were dissociable factors in this patient cannot be excluded, the finding
      of both deficits supports the possibility that occipito-temporal lesions can
      predispose to the development of autism.

PMID- 9771786
TI  - Post-arteriography cholesterol embolism.

PMID- 9771788
TI  - A "scar" and epilepsy: coup de sabre.

PMID- 9771787
TI  - Spinocerebellar ataxia type 6 with positional vertigo and acetazolamide
      responsive episodic ataxia.
AB  - The SCA6 mutation, a small expansion of a CAG repeat in a calcium channel gene
      CACNA1A, was identified in three pedigrees. Point mutations in other parts of the
      gene CACNA1A were excluded and new clinical features of SCA6 reported--namely,
      central positional nystagmus and episodic ataxia responsive to acetazolamide. The
      three allelic disorders, episodic ataxia type 2, familial hemiplegic migraine,
      and SCA6, have overlapping clinical features.

PMID- 9771789
TI  - Familial cramp due to potassium-aggravated myotonia.
AB  - Clinical, electrophysiological, and molecular genetic features were investigated
      in two patients from a family a with dominantly inherited myotonic disease,
      characterised by painful cramps, stiffness without weakness, fluctuation of
      symptoms, and cold sensitivity. A reduction in amplitude of the compound muscle
      action potential was demonstrated on cooling and administration of potassium,
      although no clinical exacerbation was seen. A heterozygote mutation Val1589Met
      was identified in the alpha-subunit of the skeletal muscle sodium channel gene in
      both patients, consistent with the diagnosis of potassium-aggravated myotonia.
      The phenotype in this family is much milder than that previously described in
      another family with a mutation at this site.

PMID- 9771790
TI  - Association between intraoperative cerebral microembolic signals and
      postoperative neuropsychological deficit: comparison between patients with
      cardiac valve replacement and patients with coronary artery bypass grafting.
AB  - OBJECTIVES: To examine the association between intraoperative cerebral
      microembolic signals (MES) and postoperative neuropsychological deficit in
      patients with valve replacement (VR) and patients with coronary artery bypass
      grafting (CABG). METHODS: Neuropsychological examination (10 tests) was performed
      1-2 days before and 2 months after surgery (VR (n=26) and CABG (n=14)). The
      intraoperative number of cerebral MES were monitored from the right middle
      cerebral artery using transcranial Doppler. RESULTS: A higher number of cerebral
      MES were detected in VR patients with neurological deficit (6/26) compared with
      those without deficit (20/26) (MES median number 2083 v 645, p=0.04). No such
      difference was found in patients with CABG (2/14 v 12/14) (MES median number 50 v
      112, p=0.2). CONCLUSION: A high number of MES were detected in patients with VR
      with neuropsychological deficit. In patients with CABG with such a deficit, a low
      number of MES were detected. This difference in number may be explained by
      relatively more gaseous emboli in the first and more solid in the second.
      However, the results in the patients with CABG should be interpreted with caution
      due to the few patients in this subgroup.

PMID- 9771792
TI  - Verbal instructional sets to normalise the temporal and spatial gait variables in
      Parkinson's disease.
AB  - Gait in Parkinson's disease is characterised by slowed velocity; shuffling, small
      steps; and absent arm swing. Drug therapy intervention is beneficial in improving
      mobility, though with prolonged use its effects may diminish. The purpose of this
      study was to examine whether Parkinsonian patients could improve their gait
      patterns in response to five instructional sets: natural walking; walking while
      deliberately swinging the arms; walking with large steps; fast walking; and
      walking while counting aloud. Eight subjects with idiopathic Parkinson's disease
      and eight age matched control subjects were tested using motion analysis. The
      findings indicated that parkinsonian patients followed the instructions which
      immediately altered a series of single walking variables. Simultaneously,
      automatically activated changes occurred in other gait variables producing more
      normal gait. The instructional set is a strategy which can aid normalisation of
      Parkinsonian gait although its benefits may depend on the stage of disease
      progression and the degree of attention to the instructions.

PMID- 9771791
TI  - Levodopa responsive parkinsonism in an adult with Huntington's disease.
AB  - A patient is reported on with Huntington's disease who, as an adult, first
      developed severe parkinsonism with bradykinesia, rigidity, postural instability
      and festinating gait. His clinical signs were similar to those of the Westphal
      variant of Huntington's disease except that he also had resting tremor and a
      supranuclear gaze palsy. Magnetic resonance imaging showed caudate and putamen
      atrophy. Genetic analysis disclosed 49 triple CAG repeats in allele 1 and 17 in
      allele 2 confirming the diagnosis of Huntington's disease. Treatment with
      levodopa produced substantial functional motor improvement with a 17 point
      reduction in the unified Parkinson's disease rating scale (UPDRS) motor subscale
      including reduction of tremor, bradykinesia, and postural instability. This is
      the first report of a patient with adult onset Huntington's disease with
      parkinsonism responsive to levodopa.

PMID- 9771793
TI  - Chronic cough in the Holmes-Adie syndrome: association in five cases with
      autonomic dysfunction.
AB  - The Holmes-Adie syndrome consists of unilateral or bilateral tonic pupils with
      near light dissociation and tendon areflexia. It is associated with autonomic
      disturbances affecting sudomotor and vasomotor function. Five such patients are
      reported on who also had a troublesome chronic dry cough, which was of unknown
      aetiology and was resistant to a range of treatments. The cough may be related to
      involvement of afferent or efferent pathways in the vagus. Chronic cough may be
      an accompaniment in the Holmes-Adie syndrome, like other forms of autonomic
      dysfunction.

PMID- 9771794
TI  - Postictal psychosis as a risk factor for mood disorders after temporal lobe
      surgery.
AB  - This study investigated the psychiatric consequences of 38 consecutive patients
      who had surgery for intractable temporal lobe epilepsy with special attention to
      postoperative mood disorders. A close interrelation between preoperative
      postictal psychosis and postoperative manic or depressive episodes was suggested.
      Left sided lobectomy augmented this correlation. Because the first sign of
      postoperative manic and depressive episodes appeared within 1 month and 2 months
      respectively, cautious psychiatric follow up for several months after surgery
      proved to be crucial to prevent postoperative suicides. Postoperative manic
      depressive episodes disappeared within the first 2 years after operation without
      exception, if treated suitably. This suggests that we do not have to preclude
      patients with postictal psychosis as surgical candidates, but measures must be
      taken to prevent postoperative depressions.

PMID- 9771795
TI  - Transient amnesia after perimesencephalic haemorrhage: the role of enlarged
      temporal horns.
AB  - OBJECTIVES: Although long term outcome of patients with perimesencephalic
      haemorrhage, a benign subset of subarachnoid haemorrhage, is excellent, some
      patients report an episode of amnesia for the first hours to days after the
      ictus. The relation between the occurrence of amnesia and the size of the
      ventricles on CT, including the temporal horns, were studied in patients with
      perimesencephalic haemorrhage. METHODS: Twenty seven consecutive patients with
      perimesencephalic haemorrhage were asked about the occurrence of amnesia. Age
      adjusted bicaudate indices and third ventricle sizes were calculated. Linear
      measurements of the temporal horn were taken in three directions: anterior
      posterior, medial-lateral, and oblique. Additionally, enlargement of the temporal
      horns was assessed with the "naked eye". RESULTS: Ten of the 27 patients reported
      an episode of transient amnesia; in these patients the mean sizes of the temporal
      horns were larger than in patients without amnesia, ranging from a factor of 1.7
      for the medial-lateral measurement to a factor of 2.3 for the anterior-posterior
      measurement. Most of the patients with amnesia had relative bicaudate indices and
      relative third ventricle sizes> 1, and all had enlarged temporal horns at "naked
      eye" assessment. CONCLUSION: About one third of patients with perimesencephalic
      haemorrhage have an episode of amnesia shortly after the bleed. The occurrence of
      amnesia is associated with enlargement of the temporal horns, and might be
      explained by temporary hippocampal dysfunction.

PMID- 9771796
TI  - The EAAT2 (GLT-1) gene in motor neuron disease: absence of mutations in
      amyotrophic lateral sclerosis and a point mutation in patients with hereditary
      spastic paraplegia.
AB  - OBJECTIVES: To investigate if sequence alterations of the excitatory amino acid
      transporter gene EAAT2 (GLT-1) may be a contributory factor to the pathogenesis
      of motor system degeneration. EAAT2 serves as a candidate gene as its reduced
      expression was reported in patients with amyotrophic lateral sclerosis (ALS).
      Furthermore, neurolathyrism, a motor neuron disease clinically related to
      hereditary spastic paraplegia (HSP), has been associated with an exogenous
      excitotoxin. METHODS: Sequence alterations were screened for in the coding region
      of EAAT2 in 55 patients with ALS and one family with autosomal dominant HSP (AD
      HSP). RESULTS: In ALS, no sequence alteration in the EAAT2 gene have been found.
      Interestingly, a heterozygous A79G mutation of the EAAT2 gene was detected in two
      of seven affected patients with AD-HSP in the same kindred. The absence of
      cosegregation with the familial disease showed that the detected variant was not
      the cause of disease. The A79G sequence variant was not found in 55 patients with
      ALS or in 50 non-neurological controls. CONCLUSION: The allelic variant of the
      EAAT2 gene in conjunction with the primary gene defect may be a modifying factor
      for the highly variable AD-HSP phenotype.

PMID- 9771797
TI  - Cerebral Erdheim-Chester disease: report of two cases with progressive cerebellar
      syndrome with dentate abnormalities on magnetic resonance imaging.
AB  - Two patients with Erdheim-Chester disease with progressive cerebellar dysfunction
      and pyramidal signs are reported on. Cerebral MRI showed bilateral increased
      signal intensity in peridentatal regions on T2 weighted sequences. Both patients
      had kidney and bone involvement, established on bone biopsy for one. One patient
      improved with steroid therapy. This contrasts with previous reports, which
      describe rare neurological manifestations and the failure of different
      therapeutic approaches.

PMID- 9771798
TI  - Familial dementia lacking specific pathological features presenting with clinical
      features of corticobasal degeneration.
AB  - A family is described in which one member presented with symptoms and signs
      suggestive of corticobasal degeneration and a sibling presented with features of
      a frontal lobe dementia. Their mother developed a presenile dementia and movement
      disorder. At postmortem examination the member with clinical corticobasal
      degeneration had non-specific pathological features. Therefore, the clinical
      features of corticobasal degeneration can occur with non-specific pathological
      changes. Within a pedigree, different members can present with different clinical
      syndromes, which may reflect variation in the distribution and severity of the
      pathological process.

PMID- 9771799
TI  - Chronic inflammatory demyelinating polyneuropathy during treatment with
      interferon-alpha.

PMID- 9771800
TI  - Posteroventral pallidotomy can ameliorate attacks of paroxysmal dystonia induced
      by exercise.

PMID- 9771801
TI  - Sudden appearance of invalidating dyskinesia-dystonia and off fluctuations after
      the introduction of levodopa in two dopaminomimetic drug naive patients with
      stage IV Parkinson's disease.

PMID- 9771802
TI  - Reversible hydromyelia in a synchronised swimmer with recurrent thoracic girdle
      pains.

PMID- 9771803
TI  - Barium carbonate intoxication: an electrophysiological study.

PMID- 9771804
TI  - Central pontine myelinolysis causes bilateral loss of deep sensitivity and
      pseudochoreoathetosis.

PMID- 9771805
TI  - Successful treatment of peripheral paraneoplastic neurological syndromes in small
      cell cancer.

PMID- 9771806
TI  - A preliminary investigation of laterality in Parkinson's disease and
      susceptibility to psychosis.

PMID- 9771807
TI  - Cerebral venous sinus thrombosis associated with 20210A mutation of the
      prothrombin gene.

PMID- 9771808
TI  - Pseudo-Argyll Robertson pupil of patients with spinocerebellar ataxia type 1
      (SCA1)

PMID- 9771809
TI  - "Non-neuroleptic malignant" syndrome.

PMID- 9771810
TI  - Corpora amylacea in hippocampal sclerosis.

PMID- 9771811
TI  - Secondary hyperkalaemic paralysis.

PMID- 9771812
TI  - Traumatic distal femoral neuropathy.

PMID- 9771813
TI  - Neuropharmacology of obesity: my receptors made me eat it.

PMID- 9771814
TI  - Manual-based group psychotherapy for bipolar disorder: a feasibility study.
AB  - BACKGROUND: The Life Goals Program is a structured, manual-based group
      psychotherapy program for bipolar disorder that seeks to improve patient
      participation in medical model treatment (phase 1) and assist patients in meeting
      functional status goals (phase 2). The goals of this initial study were (a) to
      determine whether the procedures could be exported from the authors to other
      therapists and (b) to quantify tolerability and impact of procedures on patients.
      METHOD: Four therapists across 2 sites and 29 patients from the Veterans Affairs
      (VA) Medical Center were studied in an open feasibility study. Therapists were
      trained, and subsequent compliance with manual procedures was quantified. Several
      process indices measuring tolerability and impact on patients were analyzed.
      RESULTS: Therapists covered 90% to 96% of phase 1 psychoeducational content,
      indicating excellent fidelity to manual procedures. Sixty-nine percent of
      patients completed phase 1, and participation scores were in the good to
      excellent range for 56%. Completion of phase 1 was associated with significant
      increase in knowledge about bipolar disorder. Fourteen (70%) of 20 patients
      enrolled in phase 2 reached their self-identified, behaviorally based goal (48%
      of the total sample who began phase 1 of the program). Mean +/- SD time to goal
      completion was 8.7 +/- 5.3 months (median [95% confidence interval] = 7 [5.1-12.3
      months]; range, 2-17 months). CONCLUSION: The manual-based intervention can be
      exported with fidelity to other therapists and sites (for phase 1). Data indicate
      reasonable tolerability and good achievement of process (for phases 1 and 2) for
      those who accept this group modality. Comparison with other manual-based
      psychotherapies indicates remarkable consistency regarding content for
      psychotherapy for bipolar disorder; major differences among the psychotherapies
      include mode of delivery and relative emphasis of specific components.

PMID- 9771815
TI  - Clinical features distinguishing patients with Tourette's syndrome and obsessive
      compulsive disorder from patients with obsessive-compulsive disorder without
      tics.
AB  - OBJECTIVE: It is not clear whether obsessive-compulsive disorder (OCD) in the
      context of Tourette's syndrome (TS) is the same as that disorder found in
      patients with OCD alone. This study evaluated the severity and characteristics of
      the obsessive-compulsive symptoms in adult patients with OCD and TS compared to
      adult patients with OCD alone. METHOD: Thirteen subjects with both DSM-III-R TS
      and OCD and 13 subjects with OCD alone were recruited. Obsessive-compulsive
      severity was determined by using the Yale-Brown Obsessive Compulsive Scale. The
      Tourette Syndrome Association Unified Tic Rating Scale was administered to
      determine tic severity, and the adult version of the Attention Deficit and
      Hyperactivity Checklist was used to detect a history of childhood attention
      deficit hyperactivity disorder (ADHD). RESULTS: Subjects with OCD alone had very
      few obsessions and compulsions that were not also experienced by subjects with
      both TS and OCD. In contrast, subjects with TS and OCD were significantly more
      likely to report obsessions involving nonviolent images, excessive concern with
      appearance, and need for symmetry. Touching, blinking or staring, and counting
      compulsions were also significantly more common in this group. Eight subjects
      with OCD and TS had a childhood history of ADHD, compared to none of the pure OCD
      subjects. CONCLUSION: There are subtle but definite differences in symptomatology
      of subjects with pure OCD compared to those with OCD and TS consistent with
      putative differences in pathophysiology between the 2 groups, i.e., abnormalities
      in the serotonergic system in OCD patients and serotonergic and dopaminergic
      abnormalities in those with OCD and TS. These observations may be consistent with
      genetic heterogeneity within both OCD and TS.

PMID- 9771816
TI  - Open trial of nefazodone for combat-related posttraumatic stress disorder.
AB  - BACKGROUND: Because of its ability to block 5-HT2 receptors postsynaptically and
      inhibit 5-HT reuptake presynaptically and/or its enhancement of sleep quality,
      nefazodone may be useful for symptom management in posttraumatic stress disorder
      (PTSD) patients. METHOD: Ten patients with combat-related DSM-IV posttraumatic
      stress disorder (PTSD) entered an open-label 12-week trial of nefazodone with a 4
      week follow-up, beginning with 100 mg/day and increasing as necessary to achieve
      a maximal response or until reaching a maximum dosage of 600 mg/day. RESULTS:
      Nefazodone was well tolerated, and no significant changes in sexual function were
      reported. Based on Clinical Global Impressions-Improvement scores, all 10
      patients were rated as much improved. All PTSD symptoms (except self-reported
      PTSD reexperiencing symptoms), sleep, and clinician-rated depression
      significantly improved at week 12. At follow-up, significant changes were
      maintained, and self-reported PTSD reexperiencing symptoms had also significantly
      improved. Effect sizes for all changed symptoms were moderate to large at week 12
      and at follow-up. Self-reported and clinician-rated anger significantly improved.
      Self-reported depression failed to improve. Improvement in social and
      occupational functioning was minimal. CONCLUSION: These preliminary data suggest
      that nefazodone may be effective in reducing the 3 primary PTSD symptom clusters
      and may be particularly helpful in improving sleep and decreasing anger.

PMID- 9771817
TI  - Course of psychiatric and substance abuse syndromes co-occurring with bipolar
      disorder after a first psychiatric hospitalization.
AB  - BACKGROUND: Patients with bipolar disorder frequently meet criteria for other
      psychiatric and substance abuse diagnoses. To clarify relationships among these
      disorders, the authors examined the course of syndromes co-occurring with bipolar
      disorder for 12 months after a first hospitalization. METHOD: Seventy-seven
      patients were recruited from consecutive inpatient admissions who met DSM-III-R
      criteria for bipolar disorder, manic or mixed with psychosis. The 12-month
      syndromal course of co-occurring DSM-III-R alcohol and drug abuse disorders,
      posttraumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), and
      other anxiety disorders were longitudinally recorded. RESULTS: The rates of all
      syndromes, except other anxiety disorders, were elevated. OCD demonstrated an
      interval course that frequently mirrored the course of the bipolar disorder. The
      courses of PTSD and substance abuse syndromes were separate from that of the
      bipolar disorder in many of those with both syndromes. Alcohol and drug abuse
      syndromes were strongly correlated. CONCLUSION: The obsessive-compulsive syndrome
      may represent an alternative expression of bipolar disorder in some patients. In
      contrast, PTSD appears to represent a truly separate disorder, which is possibly
      more prevalent in bipolar patients due to a shared risk factor. Substance abuse
      does not appear to simply result from attempts at self-medication or from the
      impulsivity of mania. These results suggest that future studies examining the
      course of syndromes co-occurring with bipolar disorder are warranted.

PMID- 9771819
TI  - Suicide after bright light treatment in seasonal affective disorder: a case
      report.

PMID- 9771818
TI  - Clozapine withdrawal-emergent dystonias and dyskinesias: a case series.
AB  - BACKGROUND: Severe psychotic decompensation during clozapine withdrawal has been
      reported previously. Less attention has been paid to movement disorders following
      abrupt clozapine withdrawal. This report describes 4 subjects who experienced
      severe dystonias and dyskinesias upon abrupt clozapine withdrawal. METHOD:
      Current and past medical records of 4 subjects with DSM-IV schizophrenia or
      schizo-affective disorder were reviewed. RESULTS: All subjects had a history of
      neuroleptic-induced extrapyramidal symptoms, 1 had a history of severe dystonias,
      and 1 had neuroleptic malignant syndrome. All had mild orolingual tardive
      dyskinesia prior to clozapine treatment. All subjects had received clozapine for
      several months, and 3 of the 4 subjects stopped clozapine abruptly. Two subjects
      experienced cholinergic rebound symptoms within hours, which resolved quickly.
      These subjects had severe limb-axial and neck dystonias and dyskinesias 5 to 14
      days after clozapine withdrawal. Two subjects were unable to ambulate, and 1 had
      a lurching gait. Two gagged while eating or drinking. Two subjects were returned
      to clozapine, 1 was started on low-dose risperidone treatment, and 1 was started
      on olanzapine treatment. All experienced significant improvements in their mental
      state and movement disorders. CONCLUSION: Severe movement disorders, which may be
      worse than the movements prior to clozapine treatment, and cholinergic rebound
      symptoms may occur upon abrupt clozapine withdrawal and must be recognized in
      addition to the severe psychotic decompensation noted in some patients. Patients,
      families, and caregivers must be alerted to this possibility. Where possible, a
      slow clozapine taper, the use of anticholinergic agents, and symptomatic
      treatment may help minimize these withdrawal symptoms, and reintroduction of
      clozapine or treatment with the newer atypical agents can help in the clinical
      management of these symptoms.

PMID- 9771820
TI  - Progression of abnormal involuntary movements during risperidone treatment.

PMID- 9771821
TI  - Recurrent mood shifts of premenstrual dysphoric disorder can be mistaken for
      rapid-cycling bipolar II disorder.

PMID- 9771822
TI  - Gabapentin augmentation for fluoxetine-treated patients with obsessive-compulsive
      disorder.

PMID- 9771823
TI  - Update on the management of bipolar illness.

PMID- 9771825
TI  - Early recognition of Alzheimer's disease: what is consensual? What is
      controversial? What is practical?
AB  - Alzheimer's disease is often unrecognized or misdiagnosed in its early stages.
      Despite the lack of curative treatments, there are compelling reasons why early
      recognition of Alzheimer's disease may offer substantial benefits. Early
      evaluation and diagnosis may offer opportunities to enhance patient safety, allow
      families to plan for the future, provide family education and support, and
      initiate the best treatment before more substantial neuronal loss occurs.
      Barriers to early diagnosis include failure of family or physicians to recognize
      the existence or importance of cognitive/functional changes and/or misperceptions
      regarding diagnostic requirements and treatment capabilities. There is consensus
      that high diagnostic accuracy can be achieved clinically, even by nonspecialists,
      using established criteria and practice parameters. Population-based screening
      programs for the elderly, genetic testing, yield of routine neuroimaging studies,
      and the diagnostic value of certain molecular markers remain controversial. This
      review highlights practical issues related to the initial clinical evaluation and
      differential diagnosis of Alzheimer's disease.

PMID- 9771824
TI  - Alzheimer's disease management.

PMID- 9771826
TI  - The cholinergic deficit in Alzheimer's disease.
AB  - The history of the discovery of cholinergic deficit in Alzheimer's disease is
      briefly reviewed, focusing on the cholinergic basal forebrain. The anatomy of the
      structure is discussed, and the clinical implications of pathology in this
      population of nerve cells are presented.

PMID- 9771827
TI  - Assessment of treatment-associated changes in behavior and cholinergic therapy of
      neuropsychiatric symptoms in Alzheimer's disease.
AB  - Alzheimer's disease affects multiple domains of human brain function and has
      neuropsychological, neuropsychiatric, and neurologic manifestations. Behavioral
      changes should be assessed as part of a comprehensive evaluation of the effects
      of cholinergic treatment of Alzheimer's disease. The psychometric properties,
      origin, source of behavioral information, content, and administration
      requirements of tools used to assess behavior in Alzheimer's disease affect the
      type of information garnered and the conclusions that can be derived. Assessment
      of drug-related behavioral changes can be affected by spontaneous remission of
      neuropsychiatric symptoms, differing baseline severity of behavioral
      abnormalities, uncertain magnitude of expected treatment effects, and by the
      influence of disease stages, concurrent medications, and comorbid conditions.
      Cholinergic therapies ameliorate behavioral alteration in Alzheimer's disease,
      and changes in behavior should be monitored when such therapy is initiated.

PMID- 9771829
TI  - Alzheimer's disease management.
AB  - The psychiatrist can play several important roles in the care of persons with
      Alzheimer's disease and other dementing illnesses. Diagnostic issues for which
      psychiatrists have specific skills include identifying early cases, performing a
      differential diagnosis, and distinguishing reversible depression from depression
      associated with irreversible dementia and irreversible dementia without
      depression. Treatment should include management of behavioral, noncognitive, and
      cognitive symptoms. Environmental and pharmacologic therapies have proven
      efficacious in treating noncognitive behavioral symptoms. Neuroleptic
      antipsychotic drugs are effective in treating aggressive behaviors and delusions.
      The treatment of cognitive symptoms currently rests on cholinergic enhancement.
      Finally, the psychiatrist can play important roles in educating the public and
      supporting the distressed caregiver.

PMID- 9771828
TI  - New cholinergic therapies: treatment tools for the psychiatrist.
AB  - This article reviews the current status of therapy with acetylcholine-enhancing
      compounds in the management of patients with Alzheimer's disease. The focus is on
      pivotal articles investigating the role of cholinergic augmentation strategies,
      including precursor loading and acetylcholinesterase (AChE) inhibitors, in the
      management of cognitive and noncognitive symptoms of Alzheimer's disease.
      Precursor loading strategies have been for the most part unimpressive. By
      contrast, studies with AChE inhibitors--tacrine and donepezil--have been
      promising. For patients in whom hepatotoxicity and gastrointestinal side effects
      were not problematic, tacrine improves cognitive performance and selected
      secondary psychiatric symptoms and significantly delays nursing home placement.
      Donepezil, recently approved for use in mild to moderate Alzheimer's disease,
      appears to be less toxic and better tolerated than tacrine. It improves
      performance on cognitive testing and, in one preliminary investigation,
      demonstrated a sustained drug effect over several years. Therapy with AChE
      inhibitors provides modest significant symptomatic improvement in patients with
      mild to moderate Alzheimer's disease.

PMID- 9771830
TI  - Programmed cell death.
AB  - Programmed cell death (PCD) is currently one of the most intensively studied
      areas in cell biology. Substantial evidence now exists demonstrating the integral
      role of PCD in many fundamental immunologic processes; therefore, understanding
      the mechanisms of PCD may provide advances with broad implications in
      immunobiology. This Overview provides a definition of PCD, a description of known
      PCD biochemical pathways, and finally a discussion of the implications of PCD in
      transplantation.

PMID- 9771831
TI  - Histological characterization and pharmacological control of chronic rejection in
      xenogeneic and allogeneic heart transplantation.
AB  - BACKGROUND: Chronic allograft rejection remains a major barrier to successful
      long-term allograft transplantation in humans. Chronic allograft rejection is
      characterized by the appearance of arterial lesions with concentric intimal
      thickening. This study investigates the development and control of chronic
      rejection in hamster cardiac xenografts transplanted into Lewis rats. METHODS:
      Chronic rejection in the xenograft model involves transplantation of hamster
      hearts into Lewis rats treated with leflunomide (Lef) continuously at 15
      mg/kg/day. The allograft model involves transplantation of Lewis hearts into
      Fisher-334 rats treated with cyclosporine (CsA) at 2.5 mg/kg for 5 days. RESULTS:
      The average scores of arterial intimal thickening on day 45 after transplantation
      were 1.89+/-0.43 in the xenograft and 2.50+/-0.72 in the allograft. The basic
      pathology of both xenografts and allografts undergoing chronic rejection was
      arterial intimal thickening comprising smooth muscle cell proliferation,
      mononuclear cell infiltration, and fibrosis. The majority of cells infiltrating
      the arterial intima and myocardium were T cells and macrophages. Compared with
      the allograft, intimal edema, matrix deposition and fibrinoid necrosis were
      specifically presented in the xenografts and generally involved the larger
      arteries. The predominant isotype of antibody deposited was IgM in xenografts and
      IgG in allografts. When combined Lef and CsA therapy was initiated on day 45
      after transplantation, the changes of chronic rejection were reversed in both
      xenografts and allografts by day 90. The scores of intimal thickening were
      significantly reduced to 0.97+/-0.45 and 1.48+/-0.56, respectively. CONCLUSIONS:
      We conclude that chronic rejection can be induced in xenografts under conditions
      of inadequate immunosuppression. Chronic rejection in xenografts involves
      arterial lesions that bear some histological similarities to, as well as
      differences from, those observed in chronically rejected allografts. Finally,
      combination therapy with CsA and Lef reduced the incidence and severity of the
      intimal lesions in both chronically rejecting xenografts and allografts.

PMID- 9771832
TI  - Protection against allograft rejection with intercellular adhesion molecule-1
      antisense oligodeoxynucleotides.
AB  - BACKGROUND: We designed an antisense phosphorothioate oligodeoxynucleotide
      (oligo) to specifically inhibit the expression of rat intercellular adhesion
      molecule-1 (ICAM-1) mRNA (IP-9125). METHODS: IP-9125 oligo was delivered
      intravenously by osmotic pump alone or in combination with cyclosporine (CsA) to
      recipients in order to prevent the rejection of kidney or heart allografts. In
      additional experiments, kidney allografts were perfused with IP-9125 before
      grafting. RESULTS: IP-9125 inhibited ICAM-1 mRNA and ICAM-1 protein expression in
      rat aortic endothelial cells; scrambled controls IP-12140 and IP-13944 were
      ineffective. Untreated ACI (RT1a) recipients rejected Lewis (RT1l) kidney
      allografts at a mean survival time of 8.5+/-1.1 days. A 14-day intravenous
      administration of 2.5 mg/kg/day IP-9125 prolonged the survival of kidney
      allografts to 39.2+/-16.4 days; 5.0 mg/kg/day, to 43.0+/-17.5 days; and 10.0
      mg/kg/day, to 50.4+/-21.6 days. In contrast, a scrambled control IP-12140 was not
      effective. A combination of 10 mg/kg/day IP-9125 and 1.0 mg/kg/day CsA delivered
      for 14 days synergistically extended kidney allograft survival times 88.5+/-7.5
      days. In contrast, the combination of 10.0 mg/kg/day control IP-12140 with CsA
      was ineffective (20.7+/-3.2 days) when compared with CsA alone (20.2+/-4.0 days).
      Similar results were obtained for heart transplants in recipients treated with IP
      9125 alone or in combination with CsA. Furthermore, in situ immunostaining showed
      that IP-9125 significantly reduced the expression of ICAM-1 protein in kidney
      allografts. Finally, perfusion of kidney grafts alone with 20.0 mg per 2 ml of IP
      9125 protected kidney allografts from rejection (37.5+/-7.5 days; P < 0.001),
      whereas perfusion with 20 mg per 2 ml of control IP-12140 was ineffective (12.6+/
      5.0 days). CONCLUSIONS: Rat ICAM-1 IP-9125 oligo inhibits ICAM-1 protein
      expression in vitro and in vivo as well as blocks allograft rejection when used
      for pretreatment of donors, graft perfusion, or postoperative treatment of
      recipients.

PMID- 9771833
TI  - Expression of tissue factor in hepatic ischemic-reperfusion injury of the rat.
AB  - BACKGROUND: Tissue factor (TF) is a membranous protein normally present on the
      surface of the fibroblasts and smooth muscle cells of vessels. TF is an
      initiation factor for blood coagulation, and its expression is induced on
      macrophages and endothelial cells during the inflammatory or immune response. We
      studied the significance of TF expression in warm ischemic-reperfusion injury of
      the liver using a rat model. METHODS: Following laparotomy of Lewis rats, the
      branches of the hepatic artery and portal vein leading to the median, left, and
      caudate lobes of the liver were clamped for 2 hr. The liver was reperfused after
      120 min of ischemia. Rats were killed at 0, 1, 3, 5, 8, and 12 hr after
      reperfusion, and liver tissues were harvested. TF activity was measured by the
      chromophilic substrate S-2222. TF expression was studied by immunohistochemical
      staining with the monoclonal antibody HTF-K108. RESULTS: TF activity in the blood
      showed a peak at 3 hr after reperfusion (8.9+/-0.5 U/L), then decreased and
      returned to the normal level by 12 hr (0.9+/-0.3 U/L). TF activity in ischemic
      liver tissue increased gradually over 12 hr after reperfusion (1223+/-275 U/g dry
      weight before ischemia and 2545+/-284 U/g weight at 12 hr after reperfusion).
      Histologically spotty necroses were observed in the liver tissue 5 hr after
      reperfusion. The necrotic area extended and encompassed almost all of the
      ischemic liver by 12 hr after reperfusion. Histochemically, TF staining was
      negative on the hepatocytes and slightly positive on sinusoid cells of the normal
      liver. On the other hand, TF was strongly stained, especially on the hypertrophic
      monocytic cells accumulating at the site of the necrosis, but staining was not
      evident on the necrotic hepatocytes. A slight degree of TF staining was observed
      on the alveolar epithelium of the lung, irrespective of liver ischemia and
      reperfusion. CONCLUSION: These results demonstrate that TF plays an important
      role in the development of the hepatic ischemic-reperfusion injury, and the
      subsequent microcirculatory incompetence might cause the formation of
      microthrombus and the development of necrosis.

PMID- 9771834
TI  - Complement inhibition by soluble complement receptor type 1 improves
      microcirculation after rat liver transplantation.
AB  - BACKGROUND: Recent observations provide evidence that complement is involved in
      the pathophysiology of ischemia/reperfusion injury. In this study, we assessed
      the impact of complement inhibition on hepatic microcirculation and graft
      function using a rat model of liver transplantation. METHODS: Arterialized
      orthotopic liver transplantation was performed in Lewis rats after cold
      preservation (University of Wisconsin solution, 4 degrees C, 24 h). Eight animals
      received the physiological complement regulator soluble complement receptor type
      1 (sCR1) intravenously 1 min before reperfusion. Controls received Ringer's
      solution (n=8). Microvascular perfusion, leukocyte adhesion, and Kupffer cell
      phagocytic activity were studied 30-100 min after reperfusion by in vivo
      microscopy. RESULTS: Microvascular perfusion in hepatic sinusoids was improved in
      the sCR1 group (87+/-0.7% vs. 50+/-1%; P < 0.001). The number of adherent
      leukocytes was reduced in sinusoids (68.3+/-4.7 vs. 334.1+/-15.8 [adherent
      leukocytes per mm < or = liver surface]; P < 0.001) and in postsinusoidal venules
      after sCR1 treatment (306.6+/-21.8 vs. 931.6+/-55.9 [adherent leukocytes per mm <
      or = endothelial surface]; P < 0.001). Kupffer cell phagocytic activity was
      decreased in the sCR1 group compared to controls. Postischemic bile production
      reflecting hepatocellular function was increased by almost 200% (P = 0.004) after
      complement inhibition. Plasmatic liver enzyme activity was decreased
      significantly upon sCR1 treatment, indicating reduced parenchymal cell injury.
      CONCLUSIONS: Our results provide further evidence that the complement system
      plays a decisive role in hepatic ischemia/reperfusion injury. We conclude that
      complement inhibition by sCR1 represents an effective treatment to prevent
      reperfusion injury in liver transplantation.

PMID- 9771835
TI  - Effect of complement inhibition with soluble complement receptor 1 on pig
      allotransplant lung function.
AB  - BACKGROUND: Lung dysfunction after transplantation continues to be a significant
      clinical problem. Soluble complement receptor 1 (sCR1) is a potent inhibitor of
      complement activation. We evaluated the inhibitory effect of sCR1 on complement
      activation and reperfusion injury in pig lung allografts. METHODS: In a
      randomized and blinded study, left lung transplantation was performed in 13 pigs.
      Donor lungs were flushed and then stored for 30 hr at 4 degrees C. Control pigs
      (n=7) received saline, and the treatment group (n=6) received 15 mg/kg sCR1 1 hr
      before reperfusion. One hour after reperfusion, the right pulmonary artery was
      clamped for 10 min to assess the function of the transplanted lung. Pulmonary
      function was assessed again on day 3. RESULTS: Complement inhibition was 93% in
      the sCR1 group and returned to baseline (8% inhibition) after 3 days. There was a
      trend toward a higher partial pressure of oxygen at 1 hr in the sCR1 group
      compared with the control group (mean +/- SE: 408+/-42 mmHg vs. 288+/-69 mmHg, P
      = 0.19). Alveolar ventilation was better in the sCR1 group than in the control
      group (P = 0.01) at 1 hr. Mixed venous saturation was significantly lower in the
      control group at both 1 hr (P = 0.02) and 3 days (P = 0.001). The wet/dry weight
      of the lung tissue was lower in the sCR1 group compared with the control group on
      day 3 (P < 0.05). Chemiluminescence, an index of phagocyte priming, was lower in
      the sCR1 group when cells were stimulated with complement opsonized zymosan but
      not when stimulated with zymosan or phorbol myristate acetate. CONCLUSION: sCR1
      improves ventilation, reduces pulmonary edema, and may be beneficial in improving
      posttransplant lung oxygenation.

PMID- 9771836
TI  - Treatment of chronic hepatitis B with lamivudine in renal transplant recipients.
AB  - BACKGROUND: Lamivudine is a potent inhibitor of hepatitis B virus replication.
      Little has been reported about the efficacy and safety of lamivudine in the
      treatment of chronic hepatitis B in the setting of renal transplantation.
      METHODS: Two patients were treated for chronic hepatitis B with lamivudine and
      subsequently underwent renal transplantation. Four other patients were treated
      with lamivudine for reactivation of hepatitis B after renal transplantation.
      Chronic hepatitis B was proven histologically in all the patients. The doses of
      lamivudine ranged from 100 to 150 mg/day. Hepatic enzyme and viral markers were
      monitored. RESULTS: Lamivudine was well tolerated for a median duration of 8
      months (range, 4-14 months) without significant side effects. Viral replication
      was suppressed, as evidenced by negative conversion of serum hepatitis B virus
      DNA in all the patients. Hepatic enzyme was also normalized. Modification of
      doses of immunosuppressant regimen was not required in using lamivudine in all
      patients. One patient experienced acute rejection and responded to solumedrol
      pulse therapy with normalization of graft function. Normal graft function was
      maintained in other patients while they were treated with lamivudine. CONCLUSION:
      Lamivudine was a safe and effective therapy for activated hepatitis B in renal
      transplant recipients in the short term.

PMID- 9771837
TI  - Background and prognostic implications of perireperfusion tissue injuries in
      human liver transplants: a panel histochemical study.
AB  - BACKGROUND: Hepatic graft reperfusion is associated with inflammatory processes
      of unknown relevance to the fate of graft. This study aimed to clarify this
      relevance by histochemical analyses of human hepatic grafts. METHODS: Paired
      tissue samples were taken at the end of cold preservation and 2 hr after
      reperfusion (n=39). From six additional grafts, biopsies were performed at the
      end of cold preservation only. Injury or inflammatory markers of sinusoidal
      endothelium (von Willebrand factor-related antigen [vWF]), Kupffer cells (25F9),
      platelets (CD62), neutrophil leukocytes (CD11b), interleukin (IL)-1beta,
      intercellular adhesion molecule (ICAM)-1, and HLA-DR were evaluated
      semiquantitatively by indirect immunoperoxidase staining. Steatosis was also
      evaluated by hematoxylin and eosin staining. RESULTS: vWF, CD62+ platelet
      aggregation, CD11b+ leukocytes, and IL-1beta levels increased after reperfusion,
      and these levels correlated with prereperfusion levels. Not only vWF, CD62+
      platelets, CD11b+ leukocytes, IL-1beta, ICAM-1, and steatosis after reperfusion,
      but also IL-1beta, ICAM-1, and steatosis before reperfusion correlated with
      postoperative peak transaminase. Furthermore, vWF, CD11b+ leukocytes, 25F9+
      macrophages, and ICAM-1 after reperfusion were associated with primary graft
      nonfunction and strong expressions of ICAM-1 or HLA-DR with early acute
      rejection. Although some markers (IL-1beta, CD62+ platelets, and CD11b+
      leukocytes) correlated with preharvesting parameters (donor age or length of
      intensive care unit stay), none showed any significant correlation with cold
      preservation. CONCLUSION: Synergistic inflammatory events in the hepatic graft at
      reperfusion, which have a significant impact on the later clinical course, are
      largely defined and precipitated by injury or activation of nonparenchymal cells
      preceding reperfusion or even graft harvesting.

PMID- 9771838
TI  - Anti-Gal antibody-mediated allograft rejection in alpha1,3-galactosyltransferase
      gene knockout mice: a model of delayed xenograft rejection.
AB  - BACKGROUND: The key role of anti-galactose alpha1,3-galactose (anti-alphaGal)
      xenoantibodies in initiating hyperacute xenograft rejection has been clearly
      demonstrated using a variety of in vitro and in vivo approaches. However, the
      role of anti-alphaGal antibodies in mediating post-hyperacute rejection
      mechanisms, such as antibody-dependent cellular cytoxicity, remains to be
      determined, primarily because of the lack of a small animal model with which to
      study this phenomena. METHODS: Hearts from wild-type mice were transplanted
      heterotopically into alpha1,3-galactosyltransferase knockout (Gal KO) mice, which
      like humans develop antibodies to the disaccharide galactose alpha1,3-galactose
      (Gal). At the time of rejection, hearts were examined histologically to determine
      the mechanism of rejection. RESULTS: Hearts from wild-type mice transplanted into
      high-titer anti-alphaGal recipients were rejected in 8-13 days. Histological
      examination demonstrated a cellular infiltrate consisting of macrophages (80
      90%), natural killer cells (5-10%), and T cells (1-5%). In contrast, wild-type
      hearts transplanted into low anti-Gal titer recipients demonstrated prolonged
      (>90 day) survival. However, a significant proportion (30-40%) of these underwent
      a minor rejection episode between 10 and 13 days, but then recovered
      ("accommodated"). CONCLUSIONS: The results of this study suggest that the Gal KO
      mouse is a useful small animal vascularized allograft model, in which the role of
      anti-alphaGal antibody in graft rejection can be studied in isolation from other
      rejection mechanisms. The titer of anti-alphaGal antibody was found to be the
      critical determinant of rejection. The histopathological features of rejection in
      this model are very similar to other models of delayed xenograft rejection, in
      both the timing and composition of the cellular infiltrate. The Gal KO mouse
      therefore provides a new rodent model, which will aid in the identification of
      the distinct components involved in the pathogenesis of delayed xenograft
      rejection.

PMID- 9771839
TI  - A murine model of antibody-mediated hyperacute rejection by galactose
      alpha(1,3)galactose antibodies in Gal o/o mice.
AB  - BACKGROUND: In pig-to-primate/human xenografts, hyperacute rejection of primarily
      vascularized organs usually occurs in 10-60 min and is due to the reaction of the
      recipients' natural antibodies with antigens expressed on the donor endothelium,
      the fixation of complement, and ultimately vascular stasis and hemorrhage.
      Surprisingly, the major target of the natural antibodies is the disaccharide
      galactose-alpha(1,3)galactose (Gal alpha(1,3)Gal), which is found on many
      different molecules in pig tissues and reacts with naturally occurring human anti
      pig IgM and IgG antibodies. There are a number of strategies to
      remove/block/alter Gal alpha(1,3)Gal expression in pig tissues, all of which
      involve the expression of transgenes in pigs. To overcome the difficulty of
      preclinical studies using primates, we describe a model of hyperacute rejection
      of heart transplants to Gal o/o mice, which are similar to humans in that they
      have anti-Gal alpha(1,3)Gal antibodies. METHODS: Gal o/o mice received skin or
      heart grafts from Gal+ mice or rats, and additional antibody and complement were
      provided; hyperacute rejection was monitored by observation and histology.
      RESULTS: Gal alpha(1,3)Gal+ mouse tissues (skin or heart) are not rejected by Gal
      o/o mice. This was not unexpected, as mice do not utilize alloantibody/complement
      systems satisfactorily in experimental transplantation studies. However, with the
      addition of anti-Gal alpha(1,3)Gal antibody and complement, hyperacute rejection
      of hearts can occur in 10-20 min; it is mediated by IgM, not IgG, antibodies and
      leads predominantly to tissue hemorrhage. CONCLUSION: Gal alpha(1,3)Gal antigen
      modification by expression of the H transferase cDNA leads to "indefinite"
      survival (>120 min) and no hyperacute rejection, which shows that this model is
      suitable for the study of antibody-mediated rejection of relevance to pig-to
      human xenografts.

PMID- 9771840
TI  - T-cell and major histocompatibility complex requirements for obliterative airway
      disease in heterotopically transplanted murine tracheas.
AB  - BACKGROUND: One third of human lung allografts develop chronic rejection
      manifested as obliterative bronchiolitis. Heterotopically transplanted allogeneic
      murine tracheas develop obliterative airway disease (OAD) leading to a lesion
      resembling human obliterative bronchiolitis. The purpose of this study was to
      determine the T-cell and major histocompatibility complex (MHC) molecule
      requirements of murine OAD. METHODS: BALB/c allografts and C57BL/6 (B6) isografts
      were transplanted into B6 severe combined immunodeficient (SCID) and B6 wild-type
      (WT) recipients. MHC class I-discrepant bm1 grafts, class II-discrepant bm12
      grafts, and F1(bm1 x bm12) (F1) grafts also were transplanted into B6 WT
      recipients. Grafts were harvested between days 5 and 56 following transplantation
      and evaluated histologically. RESULTS: Complete MHC-disparate allografts placed
      in WT recipients had significantly more disease than similar allografts in SCID
      recipients, and the latter were indistinguishable from isografts in either WT or
      SCID recipients, indicating a lymphocyte dependence on the disease development.
      Pathology was significantly more severe in bm1 and F1 allografts than in
      isografts recovered from B6 recipients, but bm12 allografts appeared no different
      than isografts. T-cell infiltrates in these bm12 allografts contained only CD4+
      cells, whereas infiltrates in the BALB/c, bm1, and F1 allografts manifesting OAD
      contained both CD4+ and CD8+ cells. No grafts had significant B-cell
      infiltration. CONCLUSIONS: These findings suggest that OAD relies on a host T
      cell response that includes CD8+ cells, directed against allo-class I-bearing
      donor cells within the graft.

PMID- 9771841
TI  - Successful nerve regeneration and persistence of donor cells after a limited
      course of immunosuppression in rat peripheral nerve allografts.
AB  - BACKGROUND: The origin of Schwann cells and effect of a limited course of
      immunosuppression using cyclosporine (CsA) were examined in rat peripheral nerve
      allotransplants. METHODS: Phenotypes of Schwann cells in groups without, with
      continuing, and with limited (12 weeks) CsA treatment were examined
      immunohistochemically in allogeneically and syngeneically transplanted animals
      from 4 to 36 weeks after transplantation. RESULTS: In the group receiving no CsA,
      little nerve regeneration was obtained; donor Schwann cells were rejected and
      replaced by recipient cells. In continuing and limited-course CsA groups,
      successful nerve regeneration was achieved at postoperative week 36, as was also
      observed in the syngeneic group. Schwann cells in the continuing CsA group
      remained donor-derived. In the limited-course CsA group, graft rejection and loss
      of function occurred after the withdrawal of CsA, and donor Schwann cells were
      replaced by recipient cells in the part of the graft where rejection had been
      complete. However, many donor Schwann cells remained at week 36, when the
      rejection response subsided. CONCLUSION: Possible clinical use of a limited
      course of immunosuppression was supported by this demonstration of long term
      persistence of donor Schwann cells.

PMID- 9771842
TI  - Down-modulation of host reactivity by anti-CD44 in skin transplantation.
AB  - BACKGROUND: A major goal in transplantation medicine is to achieve donor-specific
      tolerance while sustaining unaltered immunoreactivity toward donor-independent
      stimuli. Pretransplant immunization and concomitant blockade of costimulatory
      molecules may be one way to achieve this goal. We investigated whether transplant
      acceptance could be achieved by sensitization with semiallogeneic blood and
      blockade of CD44s (standard isoform) or CD44v6 (variant exon 6), since the
      adhesion molecule CD44 is known to function as a costimulatory molecule in T-cell
      activation. METHODS: Immunoregulatory regimens were examined in BDX rats that had
      received full-thickness (DA x BDX)F1 skin grafts by controlling graft acceptance
      and immunoreactivity. RESULTS: When BDX rats received full-thickness (DA x BDX)F1
      skin grafts together with either anti-CD44s or anti-CD44v6, graft rejection was
      delayed, but none of the animals accepted the graft. An analysis of
      immunoreactivity revealed reduced numbers of infiltrating lymphocytes in anti
      CD44s- as well as anti-CD44v6-treated rats. Expansion of donor-specific helper
      and cytotoxic T cells was particularly impaired in anti-CD44v6-treated rats. The
      effect of anti-CD44s could not be intensified by presensitization with donor
      derived blood. However, when rats received anti-CD44v6 concomitantly with
      presensitization, 75% permanently accepted the graft and 50% accepted a second
      graft provided they were continuously treated with anti-CD44v6 and received a low
      dose of cyclosporine (CsA) during the first weeks after grafting. The frequency
      of graft-reactive helper T cells was reduced to less than 10% of the level in
      controls, and cytotoxic T cells could hardly be detected. CONCLUSION: According
      to the in vivo and the vitro analyses of the graft and the draining lymph nodes,
      anti-CD44s blocked homing of activated lymphocytes into the graft, while anti
      CD44v6 inhibited clonal expansion of donor-specific T cells. Suppression by anti
      CD44v6 apparently functioned distinctly to cyclosporine and was most effective in
      combination with presensitization. Since expression of CD44v6 on lymphocytes is
      restricted to a short period during lymphocyte activation, anti-CD44v6 treatment
      could lead to a quite specific immunosuppression during a limited time period.

PMID- 9771843
TI  - Accessory right hepatic artery arising from the left: implications for split
      liver transplantation.
AB  - BACKGROUND: Variant arterial anatomy must be recognized and appropriately managed
      during split liver transplantation to ensure complete vascular supply to both
      grafts. We describe an accessory posterior right hepatic artery, arising from the
      left and passing behind the portal vein bifurcation. METHODS: Thirty-seven
      consecutive livers were examined during ex vivo liver-splitting procedures. An
      abnormal right accessory artery arising from the left hepatic artery was
      identified high in the porta hepatis. The anatomical variant is described and
      illustrated by methylene blue injection and arteriography. RESULTS: The anomaly
      was encountered in 2 of 37 split liver procedures. The two right lobes with the
      abnormal artery were discarded. CONCLUSION: Care should be taken during
      dissection behind the portal vein bifurcation to exclude an accessory segmental
      right hepatic artery. If present, the liver may not be suitable for splitting
      without compromising the right lobe, unless the left hepatic artery can be
      divided distal to the origin of the accessory vessel.

PMID- 9771844
TI  - Hemophagocytosis: a potential complication in small bowel transplantation.
AB  - BACKGROUND: Acquired hemophagocytosis is a histiocytic proliferation associated
      with phagocytosis of the hemopoietic elements resulting in fever, profound
      pancytopenia, hepatosplenomegaly, lymphadenopathy, and coagulopathy. Acquired
      hemophagocytic syndrome is a specific entity that can be differentiated from
      malignant histiocytosis and familial hemophagocytosis. It has been associated
      with a variety of disorders, including immunodeficiency, infection, hemopathies,
      cancer, and autoimmune diseases, as well as with the period following solid organ
      and bone marrow transplantation. METHODS: We describe a case of a fatal outcome,
      due to hemophagocytosis, after small bowel transplantation in a patient with
      systemic lupus erythematosus. RESULTS: Hemophagocytosis secondary to systemic
      lupus erythematosus has been reported to have a better response to steroid
      therapy than that associated with infection. In this case, the association of an
      autoimmune disease, high levels of immunosuppression, and posttransplant sepsis
      may have triggered the onset of hemophagocytosis. CONCLUSION: It is suggested
      that patients with systemic lupus erythematosus may represent a high-risk group
      for developing hemophagocytosis after small bowel transplantation.

PMID- 9771845
TI  - Tubular antithrombin at transplantation determines subsequent renal allograft
      function.
AB  - BACKGROUND: Antithrombin is found in the microvasculature and tubules of normal
      and transplanted human kidneys. Although depletion of vascular antithrombin is
      associated with renal allograft dysfunction, neither the distribution nor
      clinical significance of tubular antithrombin is known. METHODS: Changes in
      tubular antithrombin in biopsy specimens (n=41) obtained from donor kidneys at
      transplantation were studied immunohistochemically. The relationship between
      these changes and subsequent graft function was analyzed. RESULTS: Granular
      intracellular antithrombin was found only within the proximal tubular epithelium.
      Allografts with depleted tubular antithrombin at transplantation (n=20) had
      significantly greater plasma creatinine concentrations at posttransplant days 3
      (P < 0.001) and 5 (P < 0.03) than allografts with normal tubular antithrombin
      (n=21). Indeed, depletion of tubular antithrombin at transplantation correlated
      with the degree of graft dysfunction at 3 days after transplantation.
      CONCLUSIONS: Depleted tubular antithrombin at transplantation is associated with
      reduced early graft function, and this may identify patients at risk of a
      complicated follow-up.

PMID- 9771847
TI  - Distribution of endothelin-1 in transplanted human lungs.
AB  - BACKGROUND: This study was designed to assess which cells in transplanted lungs
      express endothelin-1 (ET-1) and if expression of the peptide can be used to
      discriminate between rejection and infection in transplanted lungs. METHODS:
      Transbronchial biopsies (n=104) from 29 human lung transplant recipients were
      stained immunohistochemically for ET-1. Cells expressing ET-1 (pneumocytes,
      endothelial cells, airway epithelial cells, lymphocytes, and macrophages) were
      quantified and correlated with clinical histopathology findings. RESULTS: ET-1
      was expressed in airway epithelial cells (93% of the biopsies), infiltrating
      macrophages (86%), and lymphocytes (19%) but not in endothelial cells or
      pneumocytes. ET-1 expression did not vary with rejection, obliterative
      bronchiolitis, or infection. ET-1 expression did not correlate with age, grade of
      rejection, pulmonary function, or time after transplantation. CONCLUSION: In
      transplanted human lungs, ET-1 is expressed in airway epithelial cells and
      infiltrating macrophages, and expression does not vary with pathological
      processes. Therefore, immunostaining for ET-1 probably cannot be used to
      discriminate between rejection and infection in transplanted lungs.

PMID- 9771846
TI  - Posttransplant therapy using high-dose human immunoglobulin (intravenous
      gammaglobulin) to control acute humoral rejection in renal and cardiac allograft
      recipients and potential mechanism of action.
AB  - BACKGROUND: Intravenous gammaglobulin (i.v.IG) contains anti-idiotypic antibodies
      that are potent inhibitors of HLA-specific alloantibodies in vitro and in vivo.
      In addition, highly HLA-allosensitized patients awaiting transplantation can have
      HLA alloantibody levels reduced dramatically by i.v.IG infusions, and subsequent
      transplantation can be accomplished successfully with a crossmatch-negative,
      histoincompatible organ. METHODS: In this study, we investigated the possible use
      of i.v.IG to reduce donor-specific anti-HLA alloantibodies arising after
      transplantation and its efficacy in treating antibody-mediated allograft
      rejection (AR) episodes. We present data on 10 patients with severe allograft
      rejection, four of whom developed AR episodes associated with high levels of
      donor-specific anti-HLA alloantibodies. RESULTS: Most patients showed rapid
      improvements in AR episodes, with resolution noted within 2-5 days after i.v.IG
      infusions in all patients. i.v.IG treatment also rapidly reduced donor-specific
      anti-HLA alloantibody levels after i.v.IG infusion. All AR episodes were
      reversed. Freedom from recurrent rejection episodes was seen in 9 of 10 patients,
      some with up to 5 years of follow-up. Results of protein G column fractionation
      studies from two patients suggest that the potential mechanism by which i.v.IG
      induces in vivo suppression is a sequence of events leading from initial
      inhibition due to passive transfer of IgG to eventual active induction of an IgM
      or IgG blocking antibody in the recipient. CONCLUSION: I.v.IG appears to be an
      effective therapy to control posttransplant AR episodes in heart and kidney
      transplant recipients, including patients who have had no success with
      conventional therapies. Vascular rejection episodes associated with development
      of donor-specific cytotoxic antibodies appears to be particularly responsive to
      i.v.IG therapy.

PMID- 9771848
TI  - Creation of the "thymoheart" allograft: implantation of autologous thymus into
      the heart prior to procurement.
AB  - BACKGROUND: A state of tolerance may be more easily achieved if fully
      vascularized and functional donor thymus is transferred to the recipient at the
      time of whole organ transplantation. METHODS: A composite "thymoheart" allograft
      was created by implanting autologous thymus into a donor heart 60-90 days before
      organ procurement. Successful intracardiac engraftment of autologous thymus was
      documented by histology and by flow cytometric analysis. RESULTS: Histology of
      the thymic autografts at explantation revealed viable thymus with preservation of
      normal thymic architecture. Cells retrieved from thymic autografts 60 days after
      implantation exhibited the same MHC class I and class II staining profiles by
      flow cytometry as cells taken from the residual native thymus. CONCLUSION: We
      have created a novel composite organ that confers vascularized and functional
      donor thymus to heart allograft recipients at the time of transplantation without
      affecting cardiac function.

PMID- 9771849
TI  - Diet, LDL oxidation, and coronary artery disease.

PMID- 9771850
TI  - Do circulating leptin concentrations reflect body adiposity or energy flux?

PMID- 9771851
TI  - Colonic mucosal folate concentrations and their association with colorectal
      cancer.

PMID- 9771852
TI  - Nutrition support and antioxidant defenses: a cause for concern?

PMID- 9771853
TI  - Effects of margarine compared with those of butter on blood lipid profiles
      related to cardiovascular disease risk factors in normolipemic adults fed
      controlled diets.
AB  - Effects of butter and 2 types of margarine on blood lipid and lipoprotein
      concentrations were compared in a controlled diet study with 23 men and 23 women.
      Table spreads, added to a common basal diet, provided 8.3% of energy as fat.
      Diets averaged 34.6% of energy as fat and 15.5% as protein. Each diet was fed for
      5 wk in a 3 x 3 Latin-square design. One margarine (TFA-M) approximated the
      average trans monoene content of trans fatty acid-containing margarines in the
      United States (17% trans fatty acids by dry wt). The other margarine (PUFA-M) was
      free of trans unsaturated fatty acids; it contained approximately twice the
      polyunsaturated fatty acid content of TFA-M (49% compared with 27%
      polyunsaturated fatty acids). The tub-type margarines had similar physical
      properties at ambient temperature. Fasting blood lipids and lipoproteins were
      determined in 2 samples taken from the subjects during the fifth week of each
      dietary treatment. Compared with butter, total cholesterol was 3.5% lower
      (P=0.009) after consumption of TFA-M and 5.4% lower (P< 0.001) after consumption
      of PUFA-M. Similarly, LDL cholesterol was 4.9% lower (P=0.005) and 6.7% lower (P<
      0.001) after consumption of TFA-M and PUFA-M, respectively. Neither margarine
      differed from butter in its effect on HDL cholesterol or triacylglycerols. Thus,
      consumption of TFA-M or PUFA-M improved blood lipid profiles for the major
      lipoproteins associated with cardiovascular risk when compared with butter, with
      a greater improvement with PUFA-M than with TFA-M.

PMID- 9771854
TI  - Reduced oxidative susceptibility of LDL from patients participating in an
      intensive atherosclerosis treatment program.
AB  - The goal of this investigation was to determine whether participation in an
      atherosclerosis treatment program would reduce the oxidative susceptibility of
      LDL from patients with coronary artery disease. The treatment program included
      intensive exercise therapy, stress management, and consumption of a diet
      containing 10% fat. The size and antioxidant and lipid contents of LDL particles
      from 25 patients were analyzed at baseline and after 3 mo of therapy. The
      susceptibility of LDL to copper-mediated oxidation was measured by a conjugated
      diene assay and headspace gas chromatography (HSGC). Atherosclerosis treatment
      significantly reduced plasma total cholesterol and apolipoprotein B
      concentrations and the molar ratio of LDL cholesterol ester to apolipoprotein B
      (P < 0.01). The LDL content of alpha-tocopherol and beta-carotene was increased
      (27% and 17%, respectively, P < 0.04) and the molar ratio of LDL cholesterol
      ester the sum of LDL alpha-tocopherol and LDL beta-carotene decreased from 159 at
      baseline to 122 at 3 mo (P < 0.01). The lag phase of LDL conjugated diene
      formation increased 24%, whereas the maximum rate of oxidation slowed 29% (P <
      0.01). As assessed by HSGC, copper-catalyzed formation of volatile lipid
      oxidation products was reduced 15% (P < 0.007); the reduction in volatiles was
      correlated with an increase in the alpha-tocopherol content of LDL (r=-0.48, P <
      0.01). The principal determinants of reduced LDL oxidative susceptibility were
      the particle contents of alpha-tocopherol and beta-carotene. To our knowledge,
      this is the first report to document a reduction in LDL oxidation in coronary
      artery disease patients undergoing atherosclerosis-reversal therapy.

PMID- 9771855
TI  - Comparison of air displacement plethysmography with dual-energy X-ray
      absorptiometry and 3 field methods for estimating body composition in middle-aged
      men.
AB  - This study was designed to compare air displacement plethysmography with dual
      energy X-ray absorptiometry (DXA) and 3 other field methods for estimation of
      body composition. Subjects were 62 healthy, white men aged 37.6+/-2.9 y (weight:
      81.8+/-11.3 kg; height: 171.5+/-4.9 cm). Body composition was also assessed by
      using body mass index, single-frequency bioelectrical impedance analysis, multi
      frequency bioelectrical impedance spectroscopy, and the skinfold-thickness
      equations of Jackson and Pollock and Durnin and Womersley. Percentage body fat
      (%BF) with the plethysmograph was 23.4+/-7.0 and with DXA was 26.0+/-7.4. The
      2.6% mean difference was significant (P< 0.05). Total error was 3.7%BF. As
      assessed by multiple regression analysis, %BF with the plethysmograph, age,
      weight, and height yielded a DXA-adjusted R2 value of 89.5% fat and an SEE of
      2.4% fat. All other models had higher SEEs and lower adjusted R2 values: 4.3% and
      66.5% for body mass index, 3.3% and 79.8% for bioelectrical impedance analysis,
      3.6% and 76.2% for bioelectrical impedance spectroscopy, 3.7% and 74.55% for the
      equations of Jackson and Pollock, and 3.9% and 71.6% for the equations of Durnin
      and Womersley, respectively. The plethysmograph also predicted fat mass and fat
      free mass more accurately than all other models, with a lower SEE and higher
      adjusted R2 value. In conclusion, although %BF was systematically underestimated,
      body composition was closely estimated with air displacement plethysmography in
      middle-aged men.

PMID- 9771857
TI  - Energy balance and thermogenesis in rats consuming nonstarch polysaccharides of
      various fermentabilities.
AB  - BACKGROUND: The equivalents of dietary protein, fat, and available carbohydrate
      as fuels for maintenance (kJ apparent metabolizable energy/kJ maintenance
      requirement) are known from classical experiments and are similar across species;
      that for nonstarch polysaccharide (NSP) is undetermined. OBJECTIVES: Our
      objectives were to determine the energy equivalent of NSP and the thermic
      responses to NSP. DESIGN: In a randomized block design, 120 rats were treated in
      groups of 10 for 28 d with a basal diet (control) supplemented with starch and 10
      different NSP treatments in amounts between 38 and 92 g/kg basal diet. Cellulose
      and starch were references. Thermic responses, deduced from body-composition
      changes and modeling of energy disposition, and energy and substrate excretion
      were determined. RESULTS: NSP had fermentabilities between 0.01 and 0.93 g/g
      intake. Fermentability, partial digestible energy, and net metabolizable energy
      values of NSP were closely related. Generally, 51% of apparent metabolizable
      energy from NSP (fermentable gross energy) met maintenance requirements. Diet
      (energy)-induced thermogenesis (DIT) was evident from whole diets. Fermentable
      NSP supplied net metabolizable energy and caused DIT. After DIT and fermentation
      were accounted for, NSP-induced thermogenesis was generally -2+/-4% (x+/-SEM) of
      gross NSP energy, except for an outlying pectic preparation, which was 33% (P<
      0.1). CONCLUSIONS: The energy equivalent of NSP was 196 (100/51) kJ/kJ, compared
      with 128, 105, and 100 for protein, fat, and glucose, respectively, from the
      classical experiments. With the exception of pectic NSP, NSP does not induce
      thermogenesis in excess of that associated with DIT and fermentation.

PMID- 9771856
TI  - Relation between circulating leptin concentrations and appetite during a
      prolonged, moderate energy deficit in women.
AB  - BACKGROUND: On the basis of observations in rodents, leptin is thought to play a
      key role in the regulation of energy expenditure and food intake, but less is
      known of its influence on ingestive behavior and energy balance in humans.
      OBJECTIVE: We examined the effect in women of a chronic energy deficit on plasma
      leptin concentrations and self-reported appetite and explored possible relations
      between leptin and appetite sensations. DESIGN: Twelve healthy women (body mass
      index, in kg/m2: 23-37) participated in a metabolic ward study in which 3 wk of
      neutral energy balance was followed by 12 wk of energy deficit (energy intake
      reduced by 2 MJ/d and energy expenditure increased by 0.8 MJ/d). Body weight and
      composition were monitored, fasting leptin concentrations were measured 4 times,
      and feelings of hunger, fullness, desire to eat, and prospective consumption were
      monitored hourly throughout the day on 7 selected days. RESULTS: Adiposity
      adjusted leptin decreased by 54% after 1 wk of a moderate energy deficit and
      remained low after 6 and 12 wk. Leptin was associated with self-reported hunger,
      desire to eat, and prospective consumption (range of r: -0.6 to -0.7, P < 0.01).
      The greatest hunger increase coincided with the largest percentage drop in
      circulating leptin and the lowest final leptin concentration. The relation
      between leptin and hunger was not influenced by amount of weight or body fat
      loss. CONCLUSIONS: These findings support the idea that leptin is a physiologic
      regulator of hunger during energy deficits in humans; the role of leptin in the
      long-term regulation of food intake warrants further study.

PMID- 9771858
TI  - Energy expenditure and net substrate utilization in men ingesting usual and high
      amounts of nonstarch polysaccharide.
AB  - BACKGROUND: Diets intrinsically high in nonstarch polysaccharides (NSPs) are
      frequently advised for body weight regulation and health, but the consequences
      for energy expenditure and fuel selection are undetermined. OBJECTIVE: We
      determined whether energy expenditure and fuel selection differ when men consume
      a diet intrinsically higher in NSP than a usual mixed diet. DESIGN: A randomized
      crossover design was used in which 12 healthy men were fed a maintenance diet for
      approximately 3 wk in a metabolic suite. By judicial choice of food exchanges,
      the usual- and high-NSP diets were similar in protein, fat, and carbohydrate
      contents. Twenty-four-hour, indirect, open-circuit calorimetry was performed,
      including measurements of total hydrogen gas and methane. Participants were
      weight stable (within 2 kg for 3 wk), entered an 11-m3 calorimetry chamber for 36
      h with measurements taken in the last 24 h, and underwent a strictly controlled
      program of moderate physical activity (1.3 x basal metabolic rate). RESULTS: The
      mean total 24-h energy expenditure and percentages from protein, fat, and
      carbohydrate metabolism were 10 MJ/d and 16%, 35%, and 48%, respectively.
      Differences (mean+/-SEM) between the 2 diets were only -0.005+/-0.130 MJ/d, 
      0.3+/-1.3%, -0.2+/-2.0%, and 0.6+/-2.2%, respectively, and were nonsignificant
      (P> 0.2). CONCLUSIONS: There was no thermogenic response to the high-NSP diet,
      which would be advantageous for body weight control, and no short-term influence
      on body composition, as may be judged from a lack of change in protein, fat, or
      carbohydrate metabolism.

PMID- 9771859
TI  - Twenty-four-hour intravenous and oral tracer studies with L-[1-13C]-2-aminoadipic
      acid and L-[1-13C]lysine as tracers at generous nitrogen and lysine intakes in
      healthy adults.
AB  - BACKGROUND: This is a continuation of investigations of the relations between
      amino acid kinetics and amino acid dietary requirements in healthy adults.
      OBJECTIVE: The aim was to investigate the 24-h pattern and rate of the metabolism
      of an L-[1-13C]-2-aminoadipic acid ([13C]AAA) tracer and of whole-body L-[1
      13C]lysine ([13C]lysine) oxidation and balance in healthy, young adults receiving
      a generous intake of lysine. DESIGN: Thirteen healthy adults were given an
      adequate, L-amino acid-based diet supplying 77 mg lysine x kg(-1) x d(-1) for 6 d
      before the tracer studies. Two subjects received [13C]AAA intravenously and 2
      received it orally; 3 subjects received [13C]lysine intravenously and 6 received
      it orally. We measured 13CO2 output, plasma [13C]AAA and [13C]lysine enrichment,
      and urinary [13C]AAA. RESULTS: [13C]AAA oxidation was estimated to be higher
      after the orally administered than after the intravenously administer tracer;
      plasma [13C]AAA was similar to urinary [13C]AAA. Whole-body lysine oxidation
      showed a rhythm that was induced by meal feeding. The intravenous [13C]lysine
      tracer gave mean estimates of lysine balances (lysine intake minus oxidation)
      that apparently were too low (-15.7 mg x kg(-1) x d(-1)) or too high (16.6 mg x
      kg(-1) x d(-1), P < 0.05 from zero balance) on the basis of urinary [13C]AAA or
      plasma [13C]lysine estimates of oxidation, respectively. For the orally
      administered tracer and plasma [13C]lysine enrichment, the mean balance was
      slightly positive (8.7 mg x kg(-1) x d(-1), P < 0.05 from zero). CONCLUSIONS: Use
      of urinary [13C]AAA as an index of the enrichment of the precursor pool did not
      appear to significantly improve the estimate of the fasting and feeding
      components of daily lysine balance. For estimates of daily, whole-body lysine
      oxidation, we propose use of plasma [13C]lysine with a 24-h, orally administered
      tracer protocol.

PMID- 9771860
TI  - Perioperative growth hormone treatment increases nitrogen and fluid balance and
      results in short-term and long-term conservation of lean tissue mass.
AB  - The surgical procedure for forming an ileoanal anastomosis with a J pouch (IAA)
      usually involves a temporary ileostomy; patients undergoing IAA surgery thus need
      to recover quickly because they return for ileostomy closure 3 mo later. We
      evaluated the effects of perioperative biosynthetic growth hormone (GH) treatment
      on short- and long-term changes in body composition and on nutritional intake.
      Patients with ulcerative colitis undergoing IAA surgery were randomly assigned to
      double-blind treatment with placebo (n=12) or 6 IU GH twice daily (n=12) from 2 d
      before to 7 d after the operation. Examinations were from 2 d before to 9 d after
      the operation and on days 30 and 90. Body composition was assessed with a dual
      energy X-ray absorptiometry scanner. The 2 groups had similar nutritional
      intakes. On postoperative day 7, placebo-treated patients had lost 4.2 kg (95%
      CI: 3.0, 5.4) total tissue mass, 3.6 kg (2.1, 5.1) lean tissue mass, and 0.5 kg (
      0.1, 1.2) fat mass. These reductions persisted 3 mo later. Compared with placebo,
      GH improved nitrogen balance, changes in lean tissue mass [gain of 4.0 kg (1.9,
      6.0), P=0.001], and changes in total tissue mass [gain of 3.2 kg (1.6, 4.9),
      P=0.001], but increased the loss of fat mass [loss of 0.7 kg (0.0, 1.5), P=0.049]
      on postoperative day 7. Three months later, the placebo-treated patients had lost
      2.4 kg (0.7, 4.2) more lean tissue mass than GH-treated patients (P=0.009),
      whereas changes in total tissue and fat mass were not significantly different.
      Hence, GH treatment enhanced the long-term regain of lean tissue mass.

PMID- 9771861
TI  - Vitamin E dose-response studies in humans with use of deuterated RRR-alpha
      tocopherol.
AB  - BACKGROUND: Supplemental vitamin E does not raise plasma alpha-tocopherol
      concentrations more than approximately 3-fold. OBJECTIVE: To elucidate the
      mechanism for the limitation in plasma alpha-tocopherol, we undertook human
      supplementation trials using incrementally increased doses of deuterated vitamin
      E. DESIGN: Plasma was obtained from 6 healthy, young adults (4 men and 2 women)
      during 3 sequential supplementation trials with doses of 15, 75, and 150 mg RRR
      alpha-tocopheryl acetate labeled with deuterium (d3-RRR-alpha-tocopheryl
      acetate). A defined diet was provided on the day of deuterated vitamin E
      administration, but otherwise subjects ate ad libitum. RESULTS: The areas under
      the curves calculated from the plasma d3-RRR-alpha-tocopherol concentrations
      increased linearly with dose--a 10-fold increase in dose resulted in a 10-fold
      increase in area under the curve. d3-RRR-alpha-Tocopherol absorption and
      incorporation into plasma did not decrease with increasing dose. At 11 h, the 15
      , 75-, and 150-mg doses resulted in 8+/-4%, 21+/-10%, and 37+/-20% labeling,
      respectively, of plasma vitamin E. Plasma total (labeled plus unlabeled) alpha
      tocopherol concentrations before supplementation were 12+/-3 micromol/L and over
      the 96 h after the dose averaged 13.3+/-2.6, 15.4+/-3.0, and 16.7+/-4.9
      micromol/L for the 15-, 75-, and 150-mg doses, respectively. CONCLUSIONS: d3-RRR
      alpha-Tocopherol was incorporated into the plasma in preference to circulating
      plasma RRR-alpha-tocopherol. This could occur if the newly absorbed d3-RRR-alpha
      tocopherol was preferentially used to replenish circulating vitamin E.

PMID- 9771862
TI  - Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently
      than does vitamin D2.
AB  - In all species tested, except humans, biological differences between vitamins D2
      and D3 are accepted as fact. To test the presumption of equivalence in humans, we
      compared the ability of equal molar quantities of vitamin D2 or D3 to increase
      serum 25-hydroxyvitamin D [25(OH)D], the measure of vitamin D nutrition. Subjects
      took 260 nmol (approximately 4000 IU) vitamin D2 (n=17) or vitamin D3 (n=55)
      daily for 14 d. 25(OH)D was assayed with a method that detects both the vitamin
      D2 and D3 forms. With vitamin D3, mean (+/-SD) serum 25(OH)D increased from
      41.3+/-17.7 nmol/L before to 64.6+/-17.2 nmol/L after treatment. With vitamin D2,
      the 25(OH)D concentration went from 43.7+/-17.7 nmol/L before to 57.4+/-13.0
      nmol/L after. The increase in 25(OH)D with vitamin D3 was 23.3+/-15.7 nmol/L, or
      1.7 times the increase obtained with vitamin D2 (13.7+/-11.4 nmol/L; P=0.03).
      There was an inverse relation between the increase in 25(OH)D and the initial
      25(OH)D concentration. The lowest 2 tertiles for basal 25(OH)D showed larger
      increases in 25(OH)D: 30.6 and 25.5 nmol/L, respectively, for the first and
      second tertiles. In the highest tertile [25(OH)D >49 nmol/L] the mean increase in
      25(OH)D was 13.3 nmol/L (P < 0.03 for comparison with each lower tertile).
      Although the 1.7-times greater efficacy for vitamin D3 shown here may seem small,
      it is more than what others have shown for 25(OH)D increases when comparing 2
      fold differences in vitamin D3 dose. The assumption that vitamins D2 and D3 have
      equal nutritional value is probably wrong and should be reconsidered.

PMID- 9771863
TI  - Dietary protein affects intestinal calcium absorption.
AB  - BACKGROUND: Changes in dietary protein in adults are associated with changes in
      urinary calcium excretion. The mechanisms underlying this effect are not
      completely understood, but alterations in intestinal absorption of calcium are
      not thought to be involved. OBJECTIVE: We reexamined this mechanism by evaluating
      the effect of 2 amounts of dietary protein (low: 0.7 g/kg; and high: 2.1 g/kg) on
      fractional calcium absorption in 7 healthy, young women. DESIGN: The experiment
      consisted of 2 wk of a well-balanced diet containing moderate amounts of calcium,
      sodium, and protein followed by 5 d of an experimental diet that contained 1 of 2
      amounts of protein and constant amounts of other nutrients known to influence
      calcium metabolism. Seven subjects received both amounts of dietary protein in
      random order. Blood and urine were sampled at baseline and on day 4. Fractional
      calcium absorption was measured by dual-stable calcium isotopes on day 5. In a
      second study of 5 additional women, we evaluated the effects of dietary fiber on
      calcitropic hormones. RESULTS: Subjects developed hypocalciuria and secondary
      hyperparathyroidism on day 4 of the low-protein diet. Urinary calcium excretion
      and the glomerular filtration rate were elevated significantly by day 4 of the
      high-protein compared with the low-protein diet. Fractional calcium absorption
      after the low-protein diet was 0.19+/-0.03, which was significantly lower than
      that after the high-protein diet (0.26+/-0.03, P=0.05). CONCLUSION: These data
      provide evidence that depressed intestinal calcium absorption explains, in part,
      low-protein-induced secondary hyperparathyroidism.

PMID- 9771864
TI  - Colonic mucosal concentrations of folate correlate well with blood measurements
      of folate status in persons with colorectal polyps.
AB  - BACKGROUND: Estimates of habitual dietary folate intake are known to be
      imprecisely correlated with systemic measures of folate status. Furthermore,
      measurements of blood folate concentrations may not accurately reflect the
      concentration of folate in tissues of interest. This issue is important for
      assessing folate status in the colorectal mucosa because low dietary intake or
      blood concentrations of folate are associated with an increased risk of
      colorectal neoplasia. OBJECTIVE: We examined whether conventional measures of
      folate in blood and a more sensitive, inverse indicator of systemic folate
      status, serum homocysteine, accurately reflected folate concentrations in human
      colonic mucosa obtained by endoscopic biopsy. DESIGN: In 30 persons with
      colorectal polyps, blood samples were taken and biopsies of normal rectosigmoid
      mucosa performed at the time of colonoscopic polypectomy. Serum, red blood cell,
      and colonic mucosal folate and serum homocysteine concentrations were measured.
      RESULTS: Serum and red blood cell folate and serum homocysteine concentrations
      accurately reflected colonic mucosal folate concentrations; among these, serum
      homocysteine correlated best with mucosal concentrations. Folate concentrations
      in the normal rectosigmoid mucosa were significantly lower in persons with
      adenomatous polyps than in those with hyperplastic polyps (P=0.04). Conventional
      measures of systemic folate status were not significantly lower in those with
      adenomas, although serum homocysteine was mildly elevated (P=0.04). CONCLUSIONS:
      Our data underscore the ability of systemic measures of folate status,
      particularly serum homocysteine, to reflect folate concentrations in the colonic
      mucosa. Nevertheless, future studies that examine the ability of folate to
      modulate colorectal carcinogenesis may benefit from direct measurement of folate
      in the colon.

PMID- 9771865
TI  - Nutrition and education: a randomized trial of the effects of breakfast in rural
      primary school children.
AB  - Hunger during school may prevent children in developing countries from benefiting
      from education. Although many countries have implemented school feeding programs,
      few programs have been rigorously evaluated. We conducted a randomized,
      controlled trial of giving breakfast to undernourished and adequately nourished
      children. The undernourished group comprised 407 children in grades 2-5 in 16
      rural Jamaican schools (weights-for-age < or = -1 SD of the National Center for
      Health Statistics references) and the adequately nourished group comprised 407
      children matched for school and class (weights-for-age >-1 SD). Both groups were
      stratified by class and school, then randomly assigned to breakfast or control
      groups. After the initial measurements, breakfast was provided every school day
      for 1 school year. Children in the control group were given one-quarter of an
      orange and the same amount of attention as children in the breakfast group. All
      children had their heights and weights measured and were given the Wide Range
      Achievement Test before and after the intervention. School attendance was taken
      from the schools' registers. Compared with the control group, height, weight, and
      attendance improved significantly in the breakfast group. Both groups made poor
      progress in Wide Range Achievement Test scores. Younger children in the breakfast
      group improved in arithmetic. There was no effect of nutritional group on the
      response to breakfast. In conclusion, the provision of a school breakfast
      produced small benefits in children's nutritional status, school attendance, and
      achievement. Greater improvements may occur in more undernourished populations;
      however, the massive problem of poor achievement levels requires integrated
      programs including health and educational inputs as well as school meals.

PMID- 9771866
TI  - Iron status, menarche, and calcium supplementation in adolescent girls.
AB  - The effects of growth, menstrual status, and calcium supplementation on iron
      status were studied over 4 y in 354 girls in pubertal stage 2 who were
      premenarcheal at baseline (x+/-SD age: 10.8+/-0.8 y). Girls were randomly
      assigned to placebo or treatment with 1000 mg Ca/d as calcium citrate malate.
      Anthropometric characteristics, bone mass, and nutritional status were measured
      biannually; ferritin was measured annually; and red blood cell indexes were
      determined at 4 y. The simultaneous effects of iron intake and menstrual status
      on serum ferritin, after change in lean body mass (LBM) was controlled for, were
      evaluated in subjects in the upper and lower quartiles of cumulative iron intake.
      The average maximal accumulation of LBM (386 g/mo; 95% CI: 372, 399) occurred 0.5
      y before the onset of menarche. Change in LBM was a significant predictor of
      serum ferritin (P < 0.0001), with a negative influence on iron status (t ratio=
      4.12). The 2 fitted mathematical models representing ferritin concentrations of
      subjects in the upper and lower quartiles of cumulative iron intake were
      significantly different (P < 0.018). The regression line of the ferritin
      concentration in menstruating girls with high iron intakes had a less negative
      slope than the line fit to serum ferritin concentrations in girls with low iron
      intakes (NS). Serum ferritin concentrations at 0, 1, 2, 3, and 4 y were not
      significantly different between groups. In addition, there was no significant
      difference between groups in any of the red blood cell indexes. In summary,
      growth spurt and menstrual status had adverse effects on iron stores in
      adolescent girls with low iron intakes (<9 mg/d), whereas long-term
      supplementation with calcium (total intake: approximately 1500 mg/d) did not
      affect iron status.

PMID- 9771867
TI  - Lipid peroxidation and antioxidant status in adults receiving lipid-based home
      parenteral nutrition.
AB  - BACKGROUND: Infusion of lipid emulsions rich in polyunsaturated fatty acids
      (PUFAs) may increase lipid peroxidation, which is counteracted mainly by
      superoxide dismutase (SOD) (a zinc-, copper-, and manganese-dependent enzyme),
      selenium-dependent glutathione peroxidase (Se-GSHPx), and alpha-tocopherol.
      OBJECTIVE: We investigated lipid peroxidation and antioxidant status in patients
      receiving home parenteral nutrition (HPN) providing variable amounts of a lipid
      emulsion rich in PUFAs, and alpha-tocopherol, zinc, copper, and manganese as
      recommended by the American Medical Association, and no selenium. DESIGN: Serum
      malondialdehyde, plasma alpha-tocopherol, selenium, Se-GSHPx, PUFAs, and red
      blood cell Se-GSHPx and SOD were evaluated in 12 patients and in 25 healthy
      control subjects. Malondialdehyde was also assessed in a group of 40 healthy
      control subjects. RESULTS: Patients had significantly higher concentrations of
      malondialdehyde and SOD and lower alpha-tocopherol concentrations and selenium
      nutritional status. Linear regression analysis showed that malondialdehyde was
      associated with the daily PUFA load (r=0.69, P< 0.03) and with plasma alpha
      tocopherol (r=-0.59, P< 0.05), but stepwise multiple regression analysis
      confirmed only the association between malondialdehyde and alpha-tocopherol;
      plasma alpha-tocopherol was associated with the daily PUFA load (r=-0.65, P<
      0.04) and with the duration of HPN (r=-0.74, P< 0.02). CONCLUSIONS: In HPN
      patients, the peroxidative stress due to lipid emulsions rich in PUFAs is
      counteracted primarily by alpha-tocopherol. The dosages of alpha-tocopherol,
      zinc, copper, and manganese recommended by the American Medical Association
      appear sufficient to sustain SOD activity but inadequate to maintain alpha
      tocopherol nutritional status. HPN formulations should be supplemented with
      selenium.

PMID- 9771868
TI  - Bringing physician nutrition specialists into the mainstream: rationale for the
      Intersociety Professional Nutrition Education Consortium.
AB  - Given the prevalence of nutritionally related chronic diseases in American
      society, the training of physicians should include a focus on the relations of
      diet to disease. Yet, despite scientific data, public interest, US government
      reports, society studies, and congressional mandates, the teaching of nutrition
      in medical schools and residency programs remains inadequate. The authority whom
      patients most wish to consult for information on health-their physician-thus
      remains insufficiently informed about the role of diet in the prevention and
      treatment of disease. New efforts must be initiated to train nutrition-literate
      physicians. The principal obstacle to nutrition literacy among physicians is the
      paucity of physician nutrition specialists (PNSs) on medical school faculties who
      can effectively advocate for change in medical school and residency curricula and
      who can serve as role models for incorporating nutrition into patient care. To
      encourage nutrition societies to unite in addressing these issues, the
      Intersociety Professional Nutrition Education Consortium was founded in 1997. The
      Consortium aims to establish educational standards for fellowship training and a
      unified mechanism for posttraining certification of PNSs, and to develop a long
      term plan to increase the pool of PNSs and surmount obstacles that currently
      impede the incorporation of nutrition education into the curricula of medical
      schools and primary-care residency programs.

PMID- 9771869
TI  - Clinical guidelines on the identification, evaluation, and treatment of
      overweight and obesity in adults: executive summary. Expert Panel on the
      Identification, Evaluation, and Treatment of Overweight in Adults.

PMID- 9771870
TI  - Calcium supplementation and estrogen.

PMID- 9771871
TI  - Difference between animal and vegetable trans fatty acids.

PMID- 9771872
TI  - Determinants of plasma homocysteine.

PMID- 9771873
TI  - Do oligosaccharides affect the intestinal absorption of calcium in humans?

PMID- 9771874
TI  - Effects of psyllium on serum lipids.

PMID- 9771875
TI  - The history and theory of the doubly labeled water technique.
AB  - Scientists have been measuring energy expenditure by using gas exchange for the
      past 200 y. This technique is based on earlier work in the 1660s. Gas exchange in
      respirometers provides accurate and repeatable measures of resting metabolic
      rate. However, it is impossible to duplicate in a respirometry chamber the
      diversity of human behaviors that influence energy expenditure. The doubly
      labeled water technique is an isotope-based method that measures the energy
      expenditure of unencumbered subjects from the divergence in enrichments of 2
      isotopic labels in body water--1 of hydrogen and 1 of oxygen. The method was
      invented in the 1950s and applied to small animals only until the early 1980s,
      mostly because of the expense. Since 1982, when the first study in humans was
      published, its use has expanded enormously. Although there is some debate over
      the precise calculation protocols that should be used, the differences between
      alternative calculations result in relatively minor effects on total energy
      expenditure estimates (approximately 6%). Validation studies show that for groups
      of subjects the method works well, but that precision is still relatively poor (8
      9%) and consequently the method is not yet sufficiently refined to provide
      estimates of individual energy expenditures.

PMID- 9771876
TI  - Energy requirements for growth and development in infancy.
AB  - Current international recommendations for energy requirements are based on >9000
      measurements of energy intake in both breast- and formula-fed infants. The
      measurement of energy intake in babies is far from straightforward and the
      possibility of significant error is great. The opportunity now exists, however,
      to compare current recommendations with measurements of total energy expenditure
      (TEE) obtained via the doubly labeled water technique. Approximately 300
      measurements of TEE in the first year of life have been made in normal, healthy
      babies. These data show that estimates of energy intake derived from the
      measurements of TEE are considerably below the current international
      recommendations. The same technique has also allowed the energy requirements of
      sick infants to be evaluated. Two examples are highlighted of infants born small
      for gestational age and infants born with cystic fibrosis. First, data collected
      from babies born small for gestational age suggest that such infants have a TEE
      and hence requirement approximately 20% above that found in infants born with a
      weight appropriate for their gestational age. This information will be relevant
      to those professionals attempting to supply optimum nutrition to babies born
      small for gestational age. Second, in cystic fibrosis it has been suggested that,
      concurrent with the basic features of the disease, there is an energy-wasting
      lesion that will increase TEE and hence energy requirement. Recent data collected
      from babies with cystic fibrosis strongly suggest that this is not the case, and
      previous data were confounded by subclinical disease status.

PMID- 9771877
TI  - Total energy expenditure and physical activity in prepubertal children: recent
      advances based on the application of the doubly labeled water method.
AB  - The prevalence of obesity in children has continued to increase despite a general
      increased awareness of health and fitness. Epidemiologic data show that the
      prevalence of obesity in children is approximately 25%, with a higher prevalence
      in some subgroups of the population. In addition, the incidence of obesity
      related diseases is dramatically increasing in children. For example, the
      incidence of type 2 diabetes in children and adolescents has increased 10-fold
      over the past decade, and this increase is more pronounced in obese persons. The
      etiology of the development of childhood obesity and subsequent disease is poorly
      understood, but is likely to be explained by alterations in the regulation of
      energy balance between energy expenditure and energy intake. It is not known
      whether obesity is caused by an increase in energy intake relative to energy
      needs, a decrease in energy expenditure relative to energy needs, or the effect
      of both. This review will focus on recent studies that have attempted to
      elucidate the etiology of childhood obesity and have increased our understanding
      of the regulation of energy balance in prepubertal children by using the doubly
      labeled water method for estimating total energy expenditure and physical
      activity-related energy expenditure. This review serves as a brief summary and
      general update of recent reviews of this topic.

PMID- 9771878
TI  - Role of energy expenditure in the development of pediatric obesity.
AB  - The role that energy expenditure plays in pediatric obesity was somewhat confused
      by early research purporting to show that, as a group, obese children have lower
      energy intakes than do lean children. On the basis of this intake data, the
      conclusion was drawn that obese persons are somehow energy efficient, leading to
      weight gain. More recent research examining energy expenditure has shown clearly
      that, as a group, obese children have higher energy expenditures than do their
      lean counterparts. With the advent of the doubly labeled water method for
      determining free-living energy expenditure, it has been shown that obese children
      underreport intake significantly more than do lean children. When measurements
      are properly adjusted for differences in body size, there are generally no major
      differences in energy expenditure between lean and obese groups. However, in some
      cross-sectional studies, a low level of physical activity has been shown to be
      related to current body fatness. In addition, longitudinal studies have shown
      that a low level of energy expenditure, particularly energy expended in physical
      activity, is associated with both body fatness and weight gain.

PMID- 9771879
TI  - Balancing energy expenditure and body weight.
AB  - It has been nearly 50 y since Mayer and coworkers hypothesized that the
      mechanisms controlling energy balance are accurate in persons with high levels of
      physical activity, but that in sedentary persons there is a threshold of physical
      activity below which these mechanisms become imprecise and that this leads to
      obesity. This hypothesis, however, was relatively untested in humans because of
      the difficulty of measuring total energy expenditure (TEE). The development of
      the doubly labeled water method has obviated this problem and we have now begun
      to test the Mayer hypothesis in humans. A review of cross-sectional data from
      doubly labeled water studies in adults provided support for the Mayer hypothesis
      in men but not in women. Men with TEE > approximately 1.75 times the resting
      metabolic rate (RMR) had lower body mass indexes than did those with lower
      expenditures. Further support for the hypothesis was obtained from a longitudinal
      study of previously obese women. Women with ratios of TEE to RMR > approximately
      1.75 gained less weight than did those with lower energy expenditures. When a
      subset of the less active women was placed in an exercise program that increased
      TEE:RMR to 1.75, weight gain was arrested. Weight gain resumed when the exercise
      program ended. The doubly labeled water method now makes it possible to
      quantitatively and objectively test a hypothesis proposed almost 50 y ago.
      Results generally support the Mayer hypothesis of a threshold of physical
      activity that protects against weight gain.

PMID- 9771880
TI  - Contributions of the doubly labeled water method to studies of energy balance in
      the Third World.
AB  - Of >250 studies on energy metabolism using the doubly labeled water (DLW)
      technique, approximately 12 full papers describe work performed in the Third
      World. Unfortunately, the term "Third World" is imprecise and the focuses of
      individual studies were too varied to allow much comparison among the data. There
      is a need to develop a more uniform approach. Useful investigations will allow
      comparisons of energy metabolism to be made in a consistent way across a variety
      of socioeconomic groups within the same country, and between the Third World and
      the developed world, with a commitment to the long term. In this way, the DLW
      method, if combined with other measurements of activity, energy intake, and body
      composition, will provide useful information on energy requirements and the
      consequences of inadequate or excessive energy intakes for the individual. Such
      investigations should be done, with standard protocols where possible, not just
      for the DLW method but also for those methods with which DLW should be
      integrated. Only if these suggestions are followed will real "value for money" be
      obtained from DLW studies in the Third World or elsewhere. In the context of
      these criteria, studies in the Third World using the DLW method have been only
      partly successful.

PMID- 9771881
TI  - Alterations in energy balance with exercise.
AB  - The doubly labeled water method for measuring average daily metabolic rate (ADMR)
      in combination with resting metabolic rate (RMR) allows one to assess the
      relation between exercise and energy balance. Three topics were included in an
      analysis of available data: 1) the limits of energy turnover in relation to
      physical performance for the achievement of energy balance, 2) the effect of an
      exercise intervention on daily energy turnover and its components, and 3) the
      effect of exercise on body composition. In the general population, physical
      activity level (PAL: ADMR/RMR) ranges between 1.2 and 2.2-2.5. There is no sex
      difference in the level of physical activity. Higher PAL values can be maintained
      by training and supplementation of the diet with energy-dense, carbohydrate-rich
      formulas. Exercise training does not influence spontaneous activity except in the
      elderly. In sedentary subjects, exercise training does not influence RMR when
      body weight is maintained. An exercise-induced increase in ADMR is about twice
      the training load. Exercise induces an increase in fat-free mass, especially in
      women, and a decrease in fat mass. Women tend to preserve energy balance and
      consequently loss of fat mass is significantly less.

PMID- 9771882
TI  - Effects of age on energy balance.
AB  - The effects of aging on energy requirements and energy balance have been studied
      by several research groups using the doubly labeled water method. The weight of
      evidence from these investigations suggests that current recommended dietary
      allowances underestimate the usual energy needs of adults of all ages, including
      older adults. In addition, doubly labeled water studies have found a significant
      negative association between body fatness and energy expenditure for physical
      activity, and a significant positive association between energy expenditure for
      physical activity and fat-free mass. Further studies are needed to refine
      estimates of energy requirements for different population groups and to address
      the role of physical activity in the prevention and treatment of obesity.

PMID- 9771883
TI  - Stimulation of NSF ATPase activity during t-SNARE priming.
AB  - N-Ethylmaleimide-sensitive factor (NSF) plays a key role in vesicular traffic by
      disassembling and priming SNARE proteins for their function in docking and
      fusion. We demonstrate that the ATPase activity of NSF is activated by alpha
      soluble NSF attachment protein (alpha-SNAP) in a complex with syntaxin 1A. In
      addition, we show that a construct consisting of the H3 domain of syntaxin IA
      (GST-synt(195-263), which does not support NSF disassembly in the presence of
      MgATP gave a larger stimulation. NSF ATPase activation was specific and did not
      occur using mutant alpha-SNAPs unable to bind GST-synt or with mutated C-termini.
      We suggest that activation of NSF ATPase activity in the SNARE complex may be
      essential to allow SNARE priming.

PMID- 9771884
TI  - Delta9-tetrahydrocannabinol induces apoptosis in C6 glioma cells.
AB  - delta9-Tetrahydrocannabinol (THC), the major active component of marijuana,
      induced apoptosis in C6.9 glioma cells, as determined by DNA fragmentation and
      loss of plasma membrane asymmetry. THC stimulated sphingomyelin hydrolysis in
      C6.9 glioma cells. THC and N-acetylsphingosine, a cell-permeable ceramide analog,
      induced apoptosis in several transformed neural cells but not in primary
      astrocytes or neurons. Although glioma C6.9 cells expressed the CBI cannabinoid
      receptor, neither THC-induced apoptosis nor THC-induced sphingomyelin breakdown
      were prevented by SR141716, a specific antagonist of that receptor. Results thus
      show that THC-induced apoptosis in glioma C6.9 cells may rely on a CBI receptor
      independent stimulation of sphingomyelin breakdown.

PMID- 9771885
TI  - Expression of bovine leukemia virus ENV glycoprotein in insect cells by
      recombinant baculovirus.
AB  - The gp51-p30 glycoprotein constituting BLV envelope was expressed in Sf-21 insect
      cells by means of recombinant baculoviruses. Post-infection cell lysates were
      analyzed, in order to define the immunologic reactivity of recombinant products.
      Oligosaccharide chains, containing N-acetylglucosamine, mannose, galactose and
      sialic acid were found on recombinant gp51-p30. In order to investigate the
      timing of transcription and translation of the glycoprotein, kinetic assays were
      carried out on cell lysates and directly in situ on Sf-21 cells during the course
      of baculovirus infection. The use of different solubilizing reagents was also
      evaluated in order to rescue recombinant glycoprotein from its subcellular
      location.

PMID- 9771886
TI  - Overexpression of the FGF-2 24-kDa isoform up-regulates IL-6 transcription in NIH
      3T3 cells.
AB  - We have isolated NIH-3T3 cell lines overexpressing the nuclear 24-kDa isoform of
      fibroblast growth factor (FGF)-2 and characterized its regulatory effect on the
      expression of interleukin-6 (IL-6) in these cells. The clone pRF5 expressing the
      highest level was able to grow in 1% serum medium to a high saturation density
      and acquired a radioresistance advantage. In pRF5 and another clone pRF1, IL-6
      RNA levels were markedly increased. Studies with IL-6 promoter constructs
      revealed that IL-6 gene up-regulation occurred at the transcriptional level and
      did not involve the AP-1 binding site. Exogenously added 18-kDa isoform of FGF-2
      (100 ng/ml) produced down-regulation of IL-6 involving an AP-1 binding site, thus
      suggesting a receptor-independent pathway for the intracellular 24-kDa isoform.

PMID- 9771887
TI  - Secretion of D-aspartic acid by the rat testis and its role in endocrinology of
      the testis and spermatogenesis.
AB  - The D-isomer of aspartic acid (D-Asp) has been found in rat testes. In the
      present study, samples of testicular venous blood plasma, rete testis fluid,
      interstitial extracellular fluid, luminal fluid from the seminiferous tubules,
      testicular parenchymal cells, epididymal spermatozoa and peripheral blood plasma
      were collected and analyzed for D-Asp by two methods, an enzymatic and a
      chromatographic HPLC method. The two methods gave very similar results for all
      samples. The highest concentrations of D-Asp (about 120 nmol/ml) were found in
      testicular venous blood plasma, with slightly lower concentrations in rete testis
      fluid (95 nmol/ml) and epididymal spermatozoa (80 nmol/g wet weight). Lower
      levels were found in testicular parenchymal cells (which would comprise mostly
      spermatids and spermatocytes), luminal fluid from the seminiferous tubules and
      interstitial extracellular fluid (26, 23 and 11 nmol/ml respectively). However,
      these values were all higher than those for peripheral blood plasma (6 nmol/ml).
      It would appear that D-Asp is being secreted by the testis mostly into the venous
      blood, passing thence into the rete testis fluid and being incorporated into the
      spermatozoa at the time or after they leave the testis. The distribution of D-Asp
      is thus quite different from that of testosterone, and its role and the reason
      for its high concentration in the male reproductive tract remain to be
      elucidated.

PMID- 9771888
TI  - Tau is phosphorylated by GSK-3 at several sites found in Alzheimer disease and
      its biological activity markedly inhibited only after it is prephosphorylated by
      A-kinase.
AB  - Alzheimer disease is characterized by a specific type of neuronal degeneration in
      which the microtubule associated protein tau is abnormally hyperphosphorylated
      causing the disruption of the microtubule network. We have found that the
      phosphorylation of human tau (tau3L) by A-kinase, GSK-3 or CK-1 inhibits its
      microtubule assembly-promoting and microtubule-binding activities. However, the
      inhibition of these activities of tau by GSK-3 is significantly increased if tau
      is prephosphorylated by A-kinase or CK-1. The most potent inhibition is observed
      by combination phosphorylation of tau with A-kinase and GSK-3. Under these
      conditions, only very few microtubules are seen by electron microscopy.
      Sequencing of 32P-labeled trypsin phosphopeptides from tau prephosphorylated by A
      kinase (using unlabeled ATP) and further phosphorylated by GSK-3 in the presence
      of [gamma-32P]ATP revealed that Ser-195, Ser-198, Ser-199, Ser-202, Thr-205, Thr
      231, Ser-235, Ser-262, Ser-356 and Ser-404 are phosphorylated, whereas if tau is
      not prephosphorylated by A-kinase, GSK-3 phosphorylates it at Thr-181, Ser-184,
      Ser-262, Ser-356 and Ser-400. These data suggest that (i) prephosphorylation of
      tau by A-kinase makes additional and different sites accessible for
      phosphorylation by GSK-3; (ii) phosphorylation of tau at these additional sites
      further inhibits the biological activity of tau in its ability to bind to
      microtubules and promote microtubule assembly. Thus a combined role of A-kinase
      and GSK-3 should be considered in Alzheimer neurofibrillary degeneration.

PMID- 9771889
TI  - Telomerase from Saccharomyces cerevisiae contains several protein subunits and
      may have different activities depending on the protein content.
AB  - Telomerase is a ribonucleoprotein responsible for maintaining telomeres during
      the cell cycle [1,2]. Here we describe a two-step purification procedure for the
      Saccharomyces cerevisiae telomerase complex. We have found that the properties
      (processivity, nuclease activity) of telomerase depend on the isolation
      procedure. Using a cross-linking approach, we have revealed several proteins that
      could be components of the telomerase complex. Furthermore, spectra of cross
      linked proteins differ in processive and non-processive telomerase complexes.

PMID- 9771890
TI  - Expression of a p16INK4a-specific ribozyme downmodulates p16INK4a abundance and
      accelerates cell proliferation.
AB  - The pl6INK4a tumor suppressor negatively regulates progression through the G1
      phase of the mammalian cell cycle. To mimic the downmodulation of p16INK4a
      commonly seen in cancer, we designed and characterized a hammerhead ribozyme
      against exon E1alpha of the murine pl6INK4a transcript. Stable expression of the
      ribozyme in murine erythroleukemia (MEL) cells reduced the endogenous pl6INK4a
      protein by more than 70% and significantly accelerated cell cycle progression.
      The specificity and efficiency of our new ribozyme suggest its possible
      application in elucidating the role of p16INK4a in fundamental biological
      processes including homeostatic tissue renewal, protection against oncogenic
      transformation, and cellular senescence.

PMID- 9771891
TI  - Loss of activation of Gs but not Gi following expression of an alpha2A
      adrenoceptor-Gi1alpha fusion protein.
AB  - Both the porcine alpha2A-adrenoceptor and a fusion protein between this receptor
      and a pertussis toxin-resistant form of Gila were stably expressed in Rat-1
      fibroblasts. The agonist UK14304 mediated a biphasic regulation of adenylyl
      cyclase activity via the isolated receptor with inhibition of the enzyme activity
      at low concentrations of the compound which was subsequently reversed at higher
      concentrations. By contrast, stimulation of the fusion protein with this agonist
      could only produce inhibition of enzyme activity. This inhibition was produced by
      activation of endogenous Gi rather than the fused alpha subunit of Gi1, as
      pertussis toxin treatment obliterated inhibitory regulation of adenylyl cyclase
      via the fusion construct. Pertussis toxin treatment potentiated stimulation of
      adenylyl cyclase via the isolated receptor but such treatment was unable to
      uncover capacity of the fusion protein to produce such an effect.

PMID- 9771892
TI  - Caspase 7-induced cleavage of kinectin in apoptotic cells.
AB  - Kinectin has been characterized as the first known receptor for the molecular
      motor kinesin, which is critically involved in microtubule-based vesicle
      transport and membrane trafficking. Here we identify kinectin as a target for
      caspase-mediated proteolysis during apoptosis. Treatment of cells with diverse
      apoptotic stimuli including TNF, anti-Fas, anticancer drugs, gamma-radiation or
      ceramide leads to rapid proteolytic cleavage of the 160-kDa form of kinectin to a
      120-kDa fragment. Evidence is provided that kinectin cleavage is mediated by
      caspase 7.

PMID- 9771893
TI  - Up-regulation of the expression of major histocompatibility complex class I
      antigens by plasmid DNA transfection in non-hematopoietic cells.
AB  - The effect of DNA on the surface expression of major histocompatibility (MHC)
      class I antigens was examined in non-hematopoietic tumor cell lines. Transfection
      with plasmid DNA via liposome or electroporation significantly increased the
      surface expression of MHC class I molecules in a transient manner. Northern blot
      analysis showed that levels of MHC class I mRNA were increased by DNA
      transfection, probably via transcriptional activation. In contrast, the
      expression of the MHC class II and beta-actin genes was not affected, suggesting
      that the up-regulation of MHC class I expression by plasmid DNA works in a gene
      specific manner.

PMID- 9771894
TI  - Altered processing of procholecystokinin in carboxypeptidase E-deficient fat
      mice: differential synthesis in neurons and endocrine cells.
AB  - The fat mouse strain exhibits a late-onset obesity syndrome associated with a
      mutation in the gene encoding carboxypeptidase E (CPE). CPE plays a central role
      in the biosynthesis of many regulatory peptides. Therefore, we examined the
      processing of procholecystokinin (proCCK) in the brain (neurons) and small
      intestine (endocrine cells) of fat/fat mice. In the brain, bioactive CCK was
      markedly reduced (7.9+/-1.0 pmol/g in fat/fat mice vs. 82.5+/-11.2 pmol/g in
      controls), but the concentration of the CPE substrate, glycylarginine-extended
      CCK, was elevated 105-fold. In contrast, the concentration of bioactive CCK in
      intestinal endocrine cells was unaffected. Endocrine cell processing was,
      nevertheless, altered with a 33-fold increase in glycyl-arginine-extended CCK.
      Interestingly, although total proCCK products were normal in the brain they were
      elevated 3-fold in the intestine, indicating that biosynthesis is upregulated in
      endocrine cells but not neurons to compensate for the processing defect. These
      results demonstrate that the CPE mutation differentially affects CCK processing
      in these two cell types. Intestinal CCK synthesis more closely resembles
      progastrin processing, suggesting the presence of an endocrine-specific
      biosynthetic regulatory mechanism not present in neurons.

PMID- 9771895
TI  - An attempt to transform class characteristics within the alcohol dehydrogenase
      family.
AB  - Human class I alcohol dehydrogenase was mutated at positions 57 and 115,
      exchanging for Asp and Arg respectively, in an attempt to introduce glutathione
      dependent formaldehyde dehydrogenase characteristics. In addition, class III
      alcohol dehydrogenase, identical to glutathione-dependent formaldehyde
      dehydrogenase, was mutated at position 115, introducing Ser or Lys. The attempted
      class transformation was partly successful considering a higher affinity for 12
      hydroxydodecanoate and a lower affinity for ethanol that was monitored for the
      class I mutant. However, the class I mutant displayed neither glutathione
      dependent formaldehyde dehydrogenase activity nor fatty acid activation of
      alcohol oxidation. Interestingly, both class III mutants showed reduced
      activities for S-hydroxymethylglutathione and 12-hydroxydodecanoate through
      increased Km, values. Overall results show that it is not possible, by single
      point mutations, to completely transform enzyme characteristics between these two
      classes of alcohol dehydrogenase.

PMID- 9771896
TI  - Deglycosylation of flavonoid and isoflavonoid glycosides by human small intestine
      and liver beta-glucosidase activity.
AB  - Flavonoid and isoflavonoid glycosides are common dietary phenolics which may be
      absorbed from the small intestine of humans. The ability of cell-free extracts
      from human small intestine and liver to deglycosylate various (iso)flavonoid
      glycosides was investigated. Quercetin 4'-glucoside, naringenin 7-glucoside,
      apigenin 7-glucoside, genistein 7-glucoside and daidzein 7-glucoside were rapidly
      deglycosylated by both tissue extracts, whereas quercetin 3,4'-diglucoside,
      quercetin 3-glucoside, kaempferol 3-glucoside, quercetin 3-rhamnoglucoside and
      naringenin 7-rhamnoglucoside remained unchanged. The Km for hydrolysis of
      quercetin 4'-glucoside and genistein 7-glucoside was approximately 32+/-12 and
      approximately 14+/-3 microM in both tissues respectively. The enzymatic activity
      of the cell-free extracts exhibits similar properties to the cytosolic broad
      specificity -glucosidase previously described in mammals.

PMID- 9771897
TI  - An Arabidopsis protein that interacts with the cytokinin-inducible response
      regulator, ARR4, implicated in the His-Asp phosphorylay signal transduction.
AB  - Previously, Arabidopsis thaliana was shown to possess a set of response
      regulators (ARR-series), which are implicated in the prokaryotic type of signal
      transduction mechanism, generally referred to as the His-Asp phosphorylay. Among
      them, ARR4 is a typical phospho-accepting response regulator, whose expression
      was recently demonstrated to be rapidly induced by a cytokinin-treatment of the
      plant. To gain insight into the presumed His-Asp phosphotransfer signaling
      mechanism as well as the role of ARR4 in this higher plant, in this study we
      adopt the widely used yeast two-hybrid system, and report the identification of
      an Arabidopsis protein that has an ability to interact physically with the
      cytokinin-inducible ARR4 response regulator.

PMID- 9771898
TI  - Thermoregulatory uncoupling in heart muscle mitochondria: involvement of the
      ATP/ADP antiporter and uncoupling protein.
AB  - Possible involvement of the ATP/ADP antiporter and uncoupling protein (UCP) in
      thermoregulatory uncoupling of oxidative phosphorylation in heart muscle has been
      studied. To this end, effects of carboxyatractylate (cAtr) and GDP, specific
      inhibitors of the antiporter and UCP, on the membrane potential of the oligomycin
      treated mitochondria from cold-exposed (6 degrees C, 48 h) and control rats have
      been measured. It is found that cAtr increases the membrane potential level in
      both cold-exposed and non-exposed groups, the effect being strongly enhanced by
      cooling. As for GDP, it is effective only in mitochondria from the cold-exposed
      rats. In these mitochondria, the coupling effect of GDP is smaller than that of
      cAtr. CDP, which does not interact with UCP, is without any influence on membrane
      potential. The cold exposure is found to increase the uncoupling efficiency of
      added natural (palmitate) or artificial (SF6847) uncouplers, the increase being
      cAtr- and GDP-sensitive in the case of palmitate. The fatty acid-free bovine
      serum albumin enhances delta psi in both cold-exposed and control groups, the
      effect being much larger in the former case. It is concluded that in heart muscle
      mitochondria the ATP/ADP antiporter is responsible for the 'mild uncoupling'
      under normal conditions and for major portion of the thermoregulatory uncoupling
      in the cold whereas the rest of thermoregulatory uncoupling is served by UCP
      (presumably by UCP2 since the UCP2 mRNA level is shown to strongly increase in
      rat heart muscle under the cold exposure conditions used).

PMID- 9771899
TI  - Intrinsic membrane association of Drosophila cysteine string proteins.
AB  - Cysteine string proteins (csps) are highly conserved constituents of vertebrate
      and invertebrate secretory organelles. Biochemical and immunoprecipitation
      experiments implied that vertebrate csps were integral membrane proteins that
      were tethered to the outer leaflet of secretory vesicles via the fatty acyl
      residues of their extensively acylated cysteine string. Independently, work of
      others suggested that Drosophila csps were peripheral membrane proteins that were
      anchored to membranes by a mechanism that was independent of the cysteine string
      and its fatty acyl residues. We extended these investigation and found first that
      sodium carbonate treatment partially stripped both csps and the integral membrane
      protein, synaptotagmin, from Drosophila membranes. Concomitantly, carbonate
      released fatty acids into the medium, arguing that it has a mild, solubilizing
      effect on these membranes. Second, we observed that Drosophila csps behaved like
      integral membrane proteins in Triton X-114 partitioning experiments. Third, we
      found that when membrane-bound csps were deacylated, they remained membrane
      bound. Moreover, it appeared that hydrophobic interactions were necessary for
      this persistent membrane association of csps. Thus, neither reducing conditions,
      urea, nor chaotropic agents displaced deacylated csps from membranes. Only
      detergents were effective in solubilizing deacylated csps. Finally, by virtue of
      the inaccessibility of deacylated csps to thiol alkylation by the membrane
      impermeant alkylating reagent, iodoacetic acid, we inferred that it was the
      cysteine string domain that mediated the membrane association of deacylated csps.
      Thus, we conclude that under physiological conditions csps are integral membrane
      proteins of secretory organelles, and that the cysteine string domain plays a
      vital role in the membrane association of these proteins.

PMID- 9771900
TI  - Expression of type VI adenylyl cyclase in the central nervous system: implication
      for a potential regulator of multiple signals in different neurotransmitter
      systems.
AB  - The aim of this study was to investigate the distribution of a calcium
      inhibitable adenylyl cyclase type VI (type VI AC) in the central nervous system
      using an antiserum directed against the N-terminus of type VI AC. Our results
      indicate that type VI AC immunoreactivity is generally expressed in many brain
      regions with different levels of intensity. Most interestingly, the majority of
      the detected type VI AC immunoreactivity is present in cells of neuronal
      phenotype. Double immunostaining of type VI AC and markers of various
      neurotransmitter systems suggest that type VI AC might participate in regulation
      of the classical neurotransmitter systems and therefore appeared to play a very
      important role in the central nervous system.

PMID- 9771901
TI  - Ribozyme processed tRNA transcripts with unfriendly internal promoter for T7 RNA
      polymerase: production and activity.
AB  - A limitation for a universal use of T7 RNA polymerase for in vitro tRNA
      transcription lies in the nature of the often unfavorable 5'-terminal sequence of
      the gene to be transcribed. To overcome this drawback, a hammerhead ribozyme
      sequence was introduced between a strong T7 RNA polymerase promoter and the tDNA
      sequence. Transcription of this construct gives rise to a 'transzyme' molecule,
      the autocatalytic activity of which liberates a 5'-OH tRNA transcript starting
      with the proper nucleotide. The method was optimized for transcription of yeast
      tRNA(Tgammar), starting with 5'-C1, and operates as well for yeast tRNA(Asp) with
      5'-U1. Although the tRNAs produced by the transzyme method are not
      phosphorylated, they are fully active in aminoacylation with k(cat) and Km
      parameters quasi identical to those of their phosphorylated counterparts.

PMID- 9771902
TI  - P2Y receptor subtypes differentially couple to inwardly-rectifying potassium
      channels.
AB  - Subtypes of P2Y receptors are well characterized with respect to their agonist
      profile but little is known about differences in their intracellular signalling
      properties. When expressed in Xenopus oocytes, both P2Y2 and P2Y6 receptors
      effectively couple to endogenous Ca2+-dependent Cl--channels. However, only P2Y2
      receptors increased currents mediated by inward-rectifier K+ channels of the
      Kir3.0 subfamily. This increase in Kir-current was sensitive to pertussis toxin,
      while activation of Ca2+-dependent Cl--channels was not. In contrast, suramin, a
      P2 receptor antagonist, inhibited activation of both channels. These observations
      suggest that, in contrast to P2Y6, P2Y2 receptors couple to two different classes
      of G proteins.

PMID- 9771903
TI  - Functional characterization of Kunitz domains in hepatocyte growth factor
      activator inhibitor type 2.
AB  - Hepatocyte growth factor activator inhibitor type 2 (HAI-2) was identified as a
      potent inhibitor of hepatocyte growth factor activator (HGF activator). The
      primary translation product of HAI-2 contains two Kunitz domains. To characterize
      their function, we introduced a point mutation into the reactive site of each
      Kunitz domain, and assayed the mutants for their HGF activator inhibitory
      activity. A point mutation in the COOH-terminal Kunitz domain did not affect the
      activity of HAI-2, whereas a point mutation in the NH2-terminal Kunitz domain
      markedly reduced the activity. These results suggest that the NH2-terminal Kunitz
      domain is mainly responsible for the HGF activator inhibitory activity of HAI-2.

PMID- 9771904
TI  - Simulated microgravity inhibits the genetic expression of interleukin-2 and its
      receptor in mitogen-activated T lymphocytes.
AB  - Experiments conducted in space in the last two decades have shown that T
      lymphocyte activation in vitro is remarkably reduced in microgravity. The data
      indicate that a failure of the expression of the interleukin-2 receptor (measured
      as protein secreted in the supernatant) is responsible of the loss of activity.
      To test such hypothesis we have studied the genetic expression of interleukin-2
      and of its receptor in concanavalin A-activated lymphocytes with the RT-PCR
      technology. Microgravity conditions were simulated in the fast rotating clinostat
      and in the random positioning machine. The latter is an instrument introduced
      recently to study gravitational effects on single cells. Our data clearly show
      that the expression of both IL-2 and IL-2Ralpha genes is significantly inhibited
      in simulated O X g. Thus full activation is prevented.

PMID- 9771905
TI  - A conserved aspartate is essential for FAD binding and catalysis in the D-amino
      acid oxidase from Trigonopsis variabilis.
AB  - To evaluate the possible contribution of Asp206 of Trigonopsis variabilis D-amino
      acid oxidase (DAO) to its flavin adenine dinucleotide (FAD) binding and catalytic
      function, six mutant enzymes were constructed by site-directed mutagenesis.
      Western immunoblot analysis revealed that a protein with an apparent molecular
      mass of about 39.2 kDa was present in the cell-free extracts of wild-type and
      mutant strains. Replacement of Asp206 with Leu, Gly, and Asn resulted in the loss
      of DAO activity and characteristic absorption spectrum for flavoenzyme, while the
      other mutant DAOs, Asp206Glu, Asp206Ser, and Asp206Ala, exhibited a similar
      spectral profile to that of wild-type enzyme and retained about 6-90% of the
      enzyme activity. These results suggested that Asp206 of T. variahilis DAO might
      play an important role in the binding of FAD.

PMID- 9771907
TI  - Residual dipolar couplings as new conformational restraints in isotropically 13C
      enriched oligosaccharides.
AB  - We report the measurement of residual dipolar couplings for l3C-enriched
      NeuNAcalpha2-3Galbeta1-4Glc in a dilute liquid-crystalline medium. These
      couplings provide long-range conformational restraints that hitherto have not
      been available for oligosaccharides. We utilise these restraints in dynamical
      simulated annealing calculations, which support current models of the solution
      behaviour of the trisaccharide.

PMID- 9771906
TI  - Matrilin-4, a new member of the matrilin family of extracellular matrix proteins.
AB  - Mouse cDNA encoding for matrilin-4 was cloned and the primary structure of this
      fourth member of the matrilin family was deduced from the nucleotide sequence.
      The protein precursor of 624 amino acids consists of a putative signal peptide,
      two vWFA-like domains linked by four epidermal growth factor-like modules and a
      potential coiled-coil alpha-helical oligomerization domain at the C-terminus. The
      predicted Mr of the mature protein is 66 442. Expression in lung, brain, sternum,
      kidney and heart was detected by Northern blot analysis of mouse mRNA.
      Additionally an alternatively spliced mRNA lacking the sequence coding for the
      first vWFA domain was found in 7 weeks old mice leading to a protein precursor of
      434 amino acids and a predicted Mr of the mature protein of 45468.

PMID- 9771908
TI  - Alpha-adrenergic inhibition of proliferation in HepG2 cells stably transfected
      with the alpha1B-adrenergic receptor through a p42MAPkinase/p21Cip1/WAF1
      dependent pathway.
AB  - Activation of alpha1B adrenergic receptors (alpha(1B)AR) promotes DNA synthesis
      in primary cultures of hepatocytes, yet expression of alpha(1B)AR in hepatocytes
      rapidly declines during proliferative events. HepG2 human hepatoma cells, which
      do not express alpha(1B)AR, were stably transfected with a rat alpha1B(AR) cDNA
      (TFG2 cells), in order to study the effects of maintained alpha(1B)AR expression
      on hepatoma cell proliferation. TFG2 cells had a decreased rate of growth
      compared to mock transfected HepG2 cells as revealed by a decrease in
      [3H]thymidine incorporation into DNA. Stimulation of alpha(1B)AR with
      phenylephrine caused a further large reduction in TFG2 cell growth, whereas no
      effect on growth was observed in mock transfected cells. Reduced cell growth
      correlated with increased percentages of cells found in G0/G1 and G2/M phases of
      the cell cycle. In TFG2 cells, phenylephrine increased p42MAPkinase activity by
      1.5- to 2.0-fold for up to 24 h and increased expression of the cyclin dependent
      kinase inhibitor protein p21Cip1/WAF1. Treatment of TFG2 cells with the specific
      MEKI inhibitor PD98059, or infection with a -/- MEK1 recombinant adenovirus
      permitted phenylephrine to increase rather than decrease [3H]thymidine
      incorporation. In addition, inhibition of MAP kinase signaling by PD98059 or MEK1
      -/- blunted the ability of phenylephrine to increase p21Cip1/WAF1 expression. In
      agreement with a role for increased p21Cip1/WAF1 expression in causing growth
      arrest, infection of TFG2 cells with a recombinant adenovirus to express
      antisense p21Cip1/WAF1 mRNA blocked the ability of phenylephrine to increase
      p21Cip1/WAF1 expression and to inhibit DNA synthesis. Antisense p21Cip1/WAF1
      permitted phenylephrine to stimulate DNA synthesis in TFG2 cells, and abrogated
      growth arrest. These results suggest that transformed hepatocytes may turn off
      the expression of alpha1B(ARs) in order to prevent the activation of a growth
      inhibitory pathway. Activation of this inhibitory pathway via alpha1B(AR) appears
      to be p42MAPkinase and p21Cip1/WAF1 dependent.

PMID- 9771909
TI  - c-myc is not involved in cadmium-elicited apoptotic pathway in porcine kidney LLC
      PK1 cells.
AB  - Cadmium chloride can induce DNA fragmentation, a biochemical characteristics of
      apoptosis in renal epithelial LLC-PK1 cells. Studies of cadmium cytotoxicity
      demonstrated that cadmium activates c-myc transcription. In this study, we
      investigated whether c-myc is a necessary component of cadmium-induced apoptosis.
      By kinetic analysis, transient activation of c-myc transcript by cadmium occurred
      before DNA fragmentation was induced by the metal, indicating an apparent
      correlation between induction of c-myc mRNA and promotion of apoptosis. However,
      even when using actinomycin D to block transcriptional activation of c-myc, or
      antisense oligodeoxynucleotide complementary to c-myc to block translation of c
      myc, cadmium could still induce apoptosis. Thus, our data show that cadmium
      elicits apoptosis by a mechanism other than regulation of c-myc expression:
      transcriptional activation of c-myc during apoptosis is not always involved in
      the cell-death events.

PMID- 9771910
TI  - Electrophysiological mechanisms for the antiarrhythmic activities of naloxone on
      cardiac tissues.
AB  - It has been reported that naloxone, an opioid antagonist, has antiarrhythmic
      activity in vivo. In Langendorff perfused rat hearts, we found that ischemia
      reperfusion-induced ventricular tachyarrhythmia reverted to normal sinus rhythm
      after the treatment with naloxone (3 approximately 10 microM). The method of
      voltage and current clamp were used to study the underlying mechanism of its
      antiarrhythmic activity on isolated cardiac myocytes. In isolated rat ventricular
      and in guinea-pig and human atrial myocytes, naloxone prolonged the action
      potential duration reversibly. In rat ventricular myocytes, naloxone (1
      approximately 30 microM) inhibited sodium current (I(Na)), transient outward
      potassium current (I(to)), and calcium current (I(Ca)). On the contrary, the
      addition of naloxone significantly increased inward rectifier potassium current
      (I(K1)). For the effect on I(Na), naloxone did not shift the inactivation curve
      of I(Na) but retarded the I(Na) recovery rate from inactivation state. Naloxone
      suppressed I(to) with a significant left-shift of the inactivation curve,
      however, the time course of I(to) recovery from inactivation was not affected. In
      guinea pig atrial myocytes, naloxone (10 microM) decreased the delayed rectifier
      K+ current (IK). These results show that naloxone exert various extent of
      inhibition on I(Na), I(to), IK and I(Ca). The prolongation of cardiac action
      potential is related to the inhibition of I(to) and IK. The antiarrhythmic
      activity of naloxone is more closely related to the inhibition of Na+ and K+
      currents rather than the blockade of myocardial opioid receptors.

PMID- 9771911
TI  - Effects of anxiolytics, diazepam and tandospirone, on immobilization stress
      induced hyperglycemia in mice.
AB  - The benzodiazepine anxiolytic diazepam did not affect immobilization-elicited
      hyperglycemia, although a high dose increased blood glucose levels in normal
      mice. The serotonergic anxiolytic tandospirone reduced immobilization-induced
      hyperglycemia dose-dependently. Hyperglycemia elicited by immobilization stress
      was completely prevented by adrenalectomy but not by pretreatment with the
      corticosterone synthesis inhibitor dexamethasone. These results suggest that the
      effects of two anxiolytics, diazepam and tandospirone, on immobilization stress
      induced hyperglycemia are quite different, although both drugs reduce anxiety.
      Furthermore, our results indicate that immobilization stress-elevated
      hyperglycemia is closely related to adrenaline release from the adrenal gland and
      that tandospirone may inhibit stress-induced hyperglycemia by modifying this
      mechanism.

PMID- 9771912
TI  - Inhibition of Na+/K+ ATPase under hypertonic conditions in rat mast cells.
AB  - Ionic fluxes that contribute to changes in membrane potential and variations of
      pHi (intracellular pH) are not well known in mast cells, although they can be
      important in the stimulus-secretion coupling. Cellular volume regulation implies
      changes in the concentration of intracellular ions, such as sodium and potassium
      and volume changes can be imposed varying the tonicity of the medium. We studied
      the physiology of sodium and examined the effect of ouabain on [22Na] entry in
      mast cells in isotonic and hypertonic media. We also recorded changes in membrane
      potential and pHi using the fluorescent dyes bis-oxonol (Bis-(1,3
      diethylthiobarbituric acid) trimethineoxonol) a n d BCECF (2',7'
      bis(carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester) in hypertonic
      conditions. The results show that [22Na] influx increases four fold in hypertonic
      solutions and it is mediated mainly by an amiloride-sensitive Na+/H+ exchanger.
      This transporter is involved in the shrinkage-activated cellular alkalinization
      and the pHi recovery is accelerated by inhibition of the Na+/K+ ATPase with
      ouabain in the absence of extracellular calcium. Under hypertonic conditions 22Na
      influx is apparently not increased by ouabain, while the Na+/K+ ATPase inhibitor
      clearly increases [22Na] uptake and also induces membrane depolarization in
      isotonic conditions. All together, these findings suggest that Na+/K+ ATPase is
      partially inhibited in hypertonic conditions.

PMID- 9771913
TI  - Endothelin ET(B) receptors counteract venoconstrictor effects of endothelin-1 in
      anesthetized rats.
AB  - The inhibitory effects of BQ 788 (3 mg/kg, i.v., ET(B)-receptor antagonist) on
      endothelin-1 (ET-1)- or IRL 1620 (ET(B)-receptor agonist)-induced changes in mean
      arterial pressure (MAP), mean circulatory filling pressure (MCFP, driving force
      of venous return), arterial resistance (RA), venous resistance (RV) and cardiac
      output (CO) were characterized in 6 groups of pentobarbital-anesthetized rats. ET
      1 or IRL 1620 (0.5, 1 and 2 nmol/kg, i.v.) dose-dependently increased MAP, RA, RV
      and MCFP and decreased CO. Maximum changes in RA, RV and CO elicited by ET-1 were
      greater than those by IRL 1620. Equimolar doses of ET-1 and IRL 1620 also caused
      similar initial transient decreases in MAP. BQ 788 alone slightly elevated MCFP,
      but did not alter other variables. The ET(B)-blocker abolished all changes
      elicited by IRL 1620, but only partially inhibited its responses on MCFP, showing
      the presence of BQ 788-insensitive receptors. BQ 788 also abolished ET-1's
      depressor response, partially inhibited its effect on MCFP, and markedly
      augmented its effects on RA, RV and CO. Thus, ET(B)-receptors counteract the
      sustained constrictor effects of ET-1 on arterial and venous resistance vessels
      Our results indicate a substantial arterial and venous dilator role for ET(B)
      receptors.

PMID- 9771914
TI  - Some chemical properties and biological role of thiazolidine compounds.
AB  - In this study we have investigated some chemical properties and the biological
      role of thiazolidine compounds, obtained by condensation of aminothiols (L- or D
      cysteine, cysteamine) with pyridoxal-5'-phosphate. These products have been
      tested in presence of rat liver extracts (supernatant and mitochondria);
      bacterial suspensions and enzymes (L- or D-aminoacid oxidase, xanthine oxidase)
      with interesting results which gives evidence to a biological role. Their
      formation in vivo may represent the regulation of intracellular levels of
      pyridoxal-5'-phosphate and aminothiols. Moreover, we have analysed the two
      diastereoisomers of the thiazolidine compounds derived from L-cysteine and D
      cysteine: we have succeeded to distinguish by NMR analysis the cis and the trans
      forms, concluding that the interconversion of the free forms is extremely rapid
      at pH 7: thus, it may be relevant for the protein bound forms.

PMID- 9771915
TI  - Up-regulation of peripheral benzodiazepine receptor system in hepatocellular
      carcinoma.
AB  - Increased number of peripheral benzodiazepine receptors (PBRs) have been found in
      some tumors outside the liver. The present study was to verify whether the PBR
      system is altered in hepatocellular carcinoma (HCC). The levels of endogenous
      benzodiazepine-like compounds (BZDs), measured by radioreceptor binding technique
      after HPLC purification and the endogenous ligand for PBRs, termed diazepam
      binding inhibitor (DBI), measured by radioimmunoassay utilizing a specific
      antibody for human DBI, were studied in the blood of 15 normal subjects, 12 liver
      cirrhosis and 10 patients with HCC. The levels of BZDs in serum were increased
      hundred fold in liver cirrhosis patients and slightly elevated in HCC patients.
      DBI was found to be increased in HCC patients. The binding recognition sites for
      PBRs (Bmax) were increased 4 to 7 fold in HCC tissue in comparison with that
      found in non-tumoral liver tissue (NTLT). On the contrary the concentrations of
      DBI were found to be significantly decreased in HCC tissue in comparison with the
      respective NTLT. These results seem to suggest an implication of PBRs and of
      their putative endogenous ligands in the metabolism of these neoplastic cells and
      possibly in their proliferation. The up-regulation of PBRs found in HCC tissue
      seems to indicate an increased functional activity of these receptors and opens
      up the possibility of new pharmacological and diagnostic approaches while the
      changes in the circulating endogenous ligands for the above receptors might be
      envisaged as early markers of tumorigenesis in liver cirrhosis.

PMID- 9771916
TI  - Phosphorylation of bovine prolactin eliminates luteotropic activity in the rat.
AB  - Phosphorylated and nonphosphorylated prolactins were isolated from bovine
      pituitaries and their luteotropic activity determined in female rats. Three
      groups of rats in day 1 of diestrus were treated i.p. twice daily for three days
      with 0.25 mg of either prolactin preparation or vehicle. Rats were sacrificed
      each day of treatment. Serum progesterone concentrations of the groups receiving
      vehicle or phosphorylated prolactin were similar and the vaginal cytology of
      these animals indicated that phosphorylated bovine prolactin (bPRL) treatment had
      not prolonged diestrus. Treatment with nonphosphorylated bPRL significantly
      increased serum progesterone concentration and the vaginal cytology indicated a
      diestrus prolonged for up to 4 days. Nonphosphorylated and phosphorylated bPRLs
      were cleared from the blood at similar rates after i.p. injection. In vitro
      receptor binding studies demonstrated that phosphorylated bPRL did not bind the
      ovarian prolactin receptor. Nonphosphorylated, but not phosphorylated, bPRL
      competed with radiolabeled bovine hormone for occupancy of rat ovarian prolactin
      receptors. These data are the first to test the activities of phosphorylated bPRL
      in vivo and indicate; 1) nonphosphorylated bPRL is luteotropic, 2) phosphorylated
      bPRL is neither luteotropic nor a prolactin receptor agonist or antagonist and 3)
      phosphorylated bPRL is not dephosphorylated in vivo rapidly enough to provide
      sufficient biologically-active bPRL to maintain luteal function.

PMID- 9771917
TI  - Regulation of delta opioid receptors by delta9-tetrahydrocannabinol in NG108-15
      hybrid cells.
AB  - In this study we employed the neuroblastoma x glioma NG 108-15 cell line as a
      model for investigating the effects of long-term activation of cannabinoid
      receptors on delta opioid receptor desensitization, down-regulation and gene
      expression. Exposure of NG 108-15 cells to (-)-delta9-tetrahydrocannabinol
      (delta9-THC) reduced opioid receptor binding, evaluated in intact cells, by
      approximately 40-45% in cells exposed for 24 h to 50 and 100 nM delta9-THC and by
      approximately 25% in cells exposed to 10 nM delta9-THC. Lower doses of delta9-THC
      (0.1 and 1 nM) or a shorter exposure time to the cannabinoid (6 h) were not
      effective. Down-regulation of 6 opioid receptors was not observed in cells
      exposed for 24 h to pertussis toxin (PTX) and then treated for 24 h with 100 nM
      delta9-THC. In cells that were exposed for 24 h to the cannabinoid, the ability
      of delta9-THC and of the delta opioid receptor agonist [D-Ser2, Leu5,
      Thr6]enkephalin to inhibit forskolin-stimulated cAMP accumulation was
      significantly attenuated. Prolonged exposure of NG 108-15 cells to 100 nM delta9
      THC produced a significant elevation of steady-state levels of delta opioid
      receptor mRNA. This effect was not observed in cells pretreated with PTX. The
      selective cannabinoid receptor antagonist SR 141716A blocked the effects elicited
      by delta9-THC on delta opioid receptor desensitization, down-regulation and gene
      expression; thus indicating that these are mediated via activation of cannabinoid
      receptors. These data demonstrate the existence, in NG 108-15 cells, of a complex
      cross-talk between the cannabinoid and opioid receptors on prolonged exposure to
      delta9-THC triggered by changes in signaling through Gi and/or G0-coupled
      receptors.

PMID- 9771918
TI  - Inhibition of restraint-induced anorexia by injected tryptophan.
AB  - Tryptophan injected at doses of 50mg/kg did not alter 24 h cumulative food intake
      and growth rate in rats. A single episode of 2 h restraint stress decreased food
      intake and growth rate of saline and tryptophan injected rats. The decreases of
      both food intake and growth rate were smaller in tryptophan injected (food intake
      23.9% p<0.05; growth rate 2.9% p<0.05) than saline injected (food intake 78.5%
      p<0.01; growth rate 6.1% p<0.01) rats suggesting that tryptophan administration
      inhibits restraint-induced anorexia. Following an acute challenge with 2h
      restraint increases of 5-hydroxytryptamine (5-HT; serotonin) and 5
      hydroxyindoleacetic acid (5-HIAA) but not tryptophan were greater in tryptophan
      injected than saline injected rats. The findings imply that tryptophan-induced
      increases of brain 5-HT and 5-HIAA have little effect on functional
      serotoninergic activity under basal conditions but a facilitatory effect on
      functional response occurs in conditions of increased serotoninergic neuronal
      activity such as during stress.

PMID- 9771919
TI  - Diacerhein blocks iron regulatory protein activation in inflamed human monocytes.
AB  - Iron Regulatory Proteins (IRPs), by modulating expression of ferritin, which
      stores excess iron in a non toxic form, and transferrin receptor, which controls
      iron uptake, are the main controller of cellular iron metabolism. During
      inflammation, modification of IRP activity may affect iron availability, free
      radical generation and cytokine gene response in inflammatory cells. In the
      present study we tested the effect of inflammatory stimuli on IRP function in a
      human monocytic-macrophagic cell line and the possibility of interfering with
      these pathways by using an antiinflammatory compound, diacerhein (DAR). IRP
      activity was enhanced by interferon gamma/lipopolysaccarhide (IFN/LPS), and this
      effect was consistently counteracted by increasing concentrations of DAR. No
      direct effect of DAR on IRP activity was found in vitro. However, in vivo,
      similar IRP activation was achieved by exposing cells to nitric oxide (NO) donors
      and the LPS/IFN-induced activation of IRP was reversed by NO inhibitors.
      Interestingly, NO-induced IRP activation was efficiently blocked by DAR. These
      data show for the first time that a clinically useful antiinflammatory compound,
      DAR, interferes with IRP activation by NO in inflammed human cells.

PMID- 9771920
TI  - The coordinate regulation of DNA synthesis and suppression of apoptosis is
      differentially regulated by the liver growth agents, phenobarbital and
      methylclofenapate.
AB  - The coordinate regulation of DNA synthesis and suppression of apoptosis was
      investigated in a rat hepatocyte cell culture system which supports high level
      induction of DNA synthesis by the peroxisome proliferator, methylclofenapate
      (MCP) (Plant, N.J. et al., 1998, Carcinogenesis, 19, 925-931). The peroxisome
      proliferators are hepatocyte mitogens in chemically defined media: glucocorticoid
      induced PPARalpha is linked to peroxisome proliferator mitogenesis (Plant, N.J.
      et al., 1998, Carcinogenesis, 19, 925-932). Phenobarbital (PB) induced moderate
      induction of DNA synthesis (200-300% of control), but the peak of induction was
      40 h after treatment. In hepatocytes that had undergone DNA synthesis, PB
      increased the proportion of binucleates by 200-300%. Both PB and MCP were able to
      suppress apoptosis in a dose-dependent manner, while the endogenous mitogen
      epidermal growth factor failed to suppress apoptosis. The suppression of
      apoptosis by MCP was reversible; withdrawal of MCP led to rapid induction of
      apoptosis. The presence of hydrocortisone is required for suppression of
      apoptosis by peroxisome proliferators, but not for PB. MCP failed to suppress
      apoptosis in primary cultures of guinea-pig hepatocytes. Comparison of the
      stability of hepatocytes labelled with bromodeoxyuridine (BrdUrd) and
      [3H]thymidine revealed that approximately 40% of cells labelled with BrdUrd were
      lost over a period of 14 days, whereas cells labelled with thymidine remained
      stable over this period. Hepatocytes were therefore treated with MCP, labelled
      with [3H]thymidine, maintained for 14 days, and peroxisome proliferator
      withdrawn. While the apoptotic index in unlabelled cells was 1.7%, no apoptosis
      was detected in labelled cells. In order to compare the mechanism of suppression
      of apoptosis, hepatocytes were cultured in the presence of either PB or MCP for
      14 days. When MCP was substituted for PB in cells cultured in the presence of PB,
      the monolayer was maintained, but when PB was used to replace MCP in cells
      cultured in the presence of MCP, the monolayer of hepatocytes degenerated
      rapidly. The results demonstrate mechanistic differences in the coordinate
      regulation of cell growth and apoptosis in hepatocytes by PB and MCP.

PMID- 9771921
TI  - Oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells transformed with c-myc
      and H-ras form high-grade glioma after stereotactic injection into the rat brain.
AB  - The oligodendrocyte-type-2 astrocyte lineage (O-2A) comprises a progenitor cell
      that is able to differentiate into an oligodendrocyte or astrocyte in vitro. The
      lineage was originally identified in the neonatal rat central nervous system but
      evidence suggests that the equivalent O-2A lineage also exists in humans. Apart
      from its putative and widely studied role in glial repair, this cell type could
      potentially be involved in malignant glioma formation. In this study we
      demonstrate that a rat O-2A progenitor cell line carrying the bacterial beta
      galactosidase reporter gene and transformed with the c-myc and H-ras oncogenes
      which has lost its differentiation capacity in vitro generates glioma-like growth
      after stereotactic injection into the adult rat brain. Tumour pathology was
      similar to human glioblastoma, suggesting that one of the pathways in the
      generation of human glioblastomas may be the transformation of adult O-2A
      progenitor cells. Parallel studies demonstrated the presence of a DNA-binding
      protein complex, termed APprog, in a panel of human glioma cell lines. This
      protein was initially identified in O-2A progenitor cells and not their
      differentiated progeny. These data lead us to propose that APprog could be used
      as an indicator of the lineage origin of gliomas.

PMID- 9771922
TI  - Analyses of mutation and loss of heterozygosity of coding sequences of the entire
      transforming growth factor beta type II receptor gene in sporadic human gastric
      cancer.
AB  - Mutations in the transforming growth factor beta type II receptor (TGFbetaRII)
      gene have been detected in several human cancer types exhibiting microsatellite
      instability. Using intron primers previously reported for examination of the
      entire coding region of the TGFbetaRII gene, 29 sporadic gastric cancers were
      screened with non-radioactive single strand conformation polymorphism and
      subsequent DNA sequencing analysis. Mutations of the TGFbetaRII gene were
      detected in three out of 29 tumors (10%). Two cases showed deletions in a
      polyadenine tract in both alleles and was positively associated with replication
      error. One case had an insertion of GA dinucleotide sequence in one allele.
      Mutations of the TGFbetaRII gene were restricted to exon 3 and other coding
      regions were not affected. Loss of heterozygosity was detected by analyzing a
      polymorphic site in intron 2. Three out of nine (33%) informative cases, which
      were all of intestinal type and advanced cases, showed loss of heterozygosity but
      neither TGFbetaRII mutation nor replication error was found in these cases.
      Immunoreactivity of TGFbetaRII in tumor tissues was reduced to a different extent
      in the gastric cancer with genetically abnormal transforming growth factor.
      Although the numbers studied are small, homozygous (A)10 deletion or loss of
      heterozygosity of TGFbetaRII is involved in tumorigenesis and progression of at
      least some part of sporadic gastric cancer.

PMID- 9771923
TI  - Induction by estrogens of methotrexate resistance in MCF-7 breast cancer cells.
AB  - Development of drug resistance is a major factor that limits the effectiveness of
      chemotherapy treatments. In this study, we determined whether estradiol or its
      metabolites 2-, 4- and 16alpha-hydroxyestrone could enhance the development of
      methotrexate resistance in the breast carcinoma cell line, MCF-7. Cells were
      incubated with the estrogens at a concentration of 10(-8) M for 12 cell doublings
      and enhancement of methotrexate resistance was measured with the Luria-Delbruck
      assay. The most efficient estrogens were the 4-hydroxyestrone and 16alpha
      hydroxyestrone, which both stimulated methotrexate resistance by 88-fold as
      compared with the control without estrogen. 2-Hydroxyestrone had an enhancement
      factor of 33-fold, whereas estradiol showed a slight effect with an enhancement
      factor of 3.2-fold. To determine whether the estrogen receptor was involved in
      the development of resistance, expression of the pS2 gene, which contains an
      estrogen-responsive element, was measured. Both estradiol and 16alpha
      hydroxyestrone stimulated expression of the pS2 gene. In contrast, 2- and 4
      hydroxyestrone did not increase the level of pS2 mRNA. This suggests that tumors
      classified as estrogen receptor negative could also develop methotrexate
      resistance as the result of exposure to estrogens. The status of the tumor
      suppressor gene p53 was analyzed in methotrexate sensitive and resistant clones.
      In all the methotrexate resistant clones analyzed, the western blots indicated
      that the p53 protein was still present and transcriptionally competent, as
      measured by its capacity to stimulate transcription of the p21waf1/cip1 gene
      following UVB irradiation. However, the basal level of p53 was higher in
      resistant clones and addition of 2- or 4-hydroxyestrone increased p53 to levels
      equivalent to those observed following UVB irradiation. However, this induction
      of p53 accumulation by estrogens failed to stimulate the transcription of
      p21waf1/cip1, which indicates that a transcriptionally inactive form of p53
      accumulated in methotrexate resistant cells.

PMID- 9771924
TI  - Effect of pre-conceptional external or internal irradiation of N5 male mice and
      the risk of leukemia in their offspring.
AB  - Male mice of the N5 strain were exposed to a unique external X-ray dose of 500
      cGy, or to i.p. injections of tritiated water (HTO) over a 30 day period, which
      resulted in an estimated total internal exposure of 150 cGy. The paternal X-ray
      irradiation resulted in a marginally significant (P = 0.07) doubling of the
      leukemia/lymphoma rate in the offspring, over a 1 year observation period. The
      constitutive gene expression of granulocyte-macrophage colony stimulating factor
      (GM-CSF) and tumour necrosis factor (TNF) (two cytokines associated with
      hematopoiesis and immune response) spontaneously diminished between the ages of 6
      months and 12 months in the bone marrows and in the spleens of these mice, and
      paternal X-ray exposure influenced the statistical significance of this
      diminution. Male exposure to HTO resulted in a statistically significant several
      fold increase of leukemia incidence among the young offspring. However this
      increase tended to diminish as older mice were observed, and was no longer
      significant at 1 year of age. The overall leukemia incidence in the offspring of
      the HTO-exposed fathers was significantly dependent on the maturation stage of
      the sperm-forming cells during the HTO exposure, which suggests an influence of
      such an exposure.

PMID- 9771925
TI  - Stress protein expression in rat liver during tumour promotion: induction of heat
      shock protein 27 in hepatocytes exposed to 2-acetylaminofluorene.
AB  - Exposure of cells to a variety of stresses such as heat, radiation and
      xenobiotics leads to increased expression of heat-shock proteins (HSPs). HSPs
      protect cells against irreversible protein damage and are involved in adaptive
      responses to stress stimuli. Some HSPs are overexpressed in neoplasias, possibly
      contributing to the increased drug tolerance often observed in such lesions. We
      have studied HSP expression in two experimental rat hepatocarcinogenesis models.
      Our aim was to clarify whether they are involved in stress adaptation in
      hepatocytes during carcinogen exposure, and whether HSPs may contribute to
      xenobiotic resistance in preneoplastic lesions. The complete carcinogen 2
      acetylaminofluorene (AAF) was used in a continuous feeding protocol, and in the
      resistant hepatocyte model where the growth of diethylnitrosamine initiated
      lesions is efficiently promoted. Of the HSPs tested, only heat-shock protein 27
      (hsp27) was induced during continuous AAF exposure. After 4 weeks of feeding AAF,
      increased hsp27 expression was noted in hepatocytes in perivenous areas of the
      liver lobule, possibly mediating an adaptive response to stress caused by
      reactive AAF metabolites. Enzyme altered preneoplastic foci were not found to
      overexpress HSPs. Thus, HSP induction does not seem to be a general mechanism
      underlying the increased stress tolerance observed in such lesions.

PMID- 9771926
TI  - Hemoglobin and albumin adducts of benzene oxide among workers exposed to high
      levels of benzene.
AB  - Benzene oxide (BO) reacts with cysteinyl residues in hemoglobin (Hb) and albumin
      (Alb) to form protein adducts (BO-Hb and BO-Alb), which are presumed to be
      specific biomarkers of exposure to benzene. We analyzed BO-Hb in 43 exposed
      workers and 42 unexposed controls, and BO-Alb in a subsample consisting of 19
      workers and 19 controls from Shanghai, China, as part of a larger cross-sectional
      study of benzene biomarkers. The adducts were analyzed by gas chromatography-mass
      spectrometry following reaction of the protein with trifluoroacetic anhydride and
      methanesulfonic acid. When subjects were divided into controls (n = 42) and
      workers exposed to < or =31 (n = 21) and >31 p.p.m. (n = 22) benzene, median BO
      Hb levels were 32.0, 46.7 and 129 pmol/g globin, respectively (correlation with
      exposure: Spearman r = 0.67, P < 0.0001). To our knowledge, these results
      represent the first observation in humans that BO-Hb levels are significantly
      correlated with benzene exposure. Median BO-Alb levels in these 3 groups were 103
      (n = 19), 351 (n = 7) and 2010 (n = 12) pmol/g Alb, respectively, also reflecting
      a significant correlation with exposure (Spearman r = 0.90, P < 0.0001). The
      blood dose of BO predicted from both Hb and Alb adducts was very similar. These
      results clearly affirm the use of both Hb and Alb adducts of BO as biomarkers of
      exposure to high levels of benzene. As part of our investigation of the
      background levels of BO-Hb and BO-Alb found in unexposed persons, we analyzed
      recombinant human Hb and Alb for BO adducts. Significant levels of both BO-Hb
      (19.7 pmol/g) and BO-Alb (41.9 pmol/g) were detected, suggesting that portions of
      the observed background adducts reflect an artifact of the assay, while other
      portions are indicative of either unknown exposures or endogenous production of
      adducts.

PMID- 9771927
TI  - Hormone-induced refractoriness to mammary carcinogenesis in Wistar-Furth rats.
AB  - One of the most consistent results in the epidemiology of human breast cancer is
      the inverse relationship of risk and early full-term parity. The goal of this
      study was to investigate the molecular mechanisms through which early full-term
      pregnancy protects the breast from cancer development. We used Wistar-Furth (WF)
      rats as our experimental system and mimicked pregnancy using estrogen and
      progesterone (E/P). Sexually mature female rats were treated with steroid
      hormones for 21 days and after 28 days of gland involution, the rats were
      administered MNU. Rats that received a high dose of 20 microg E and 20 mg P
      exhibited an 82% reduction in the incidence of mammary adenocarcinomas as
      compared to the rats receiving only blank pellets. Decreasing doses of E/P were
      partially protective suggesting that complete differentiation of the gland was
      not required for refractoriness. We measured the RNA expression levels of several
      target genes involved in the regulation of mammary cell proliferation and/or
      differentiation including estrogen receptor (ER) and progesterone receptor (PR),
      cyclins D1 and D2, the cell cycle inhibitors p16, p21 and p27, and the tumor
      suppressor p53. At the time of MNU treatment we found no significant differences
      in the expression of these genes, with the possible exception of p21, indicating
      that hormone treatment did not result in constitutive changes in expression
      levels. The numbers of apoptotic cells were low and comparable in the hormone
      exposed and age-matched virgin gland (AMV) at the time of carcinogen challenge
      and remained low for 8 days after MNU treatment. The number of BrdU-labeled cells
      at the time of carcinogen challenge were also low in both the AMV (1.8%) and
      hormone exposed (0.8%) animals. In contrast, cell proliferation in the AMV (5.7%)
      was significantly different from both the parous involuted (1.2%) and the E/P
      treated involuted (1.5%) animals 8 days after MNU treatment. We interpret these
      data to indicate that hormone treatment results in mammary epithelial cells that
      have persistent alterations in intracellular pathways governing proliferation
      responses to carcinogens.

PMID- 9771928
TI  - Quercetin inhibits hydrogen peroxide (H2O2)-induced NF-kappaB DNA binding
      activity and DNA damage in HepG2 cells.
AB  - We have investigated the effect of the plant-derived flavonoid quercetin in
      relation to potential oxidant and antioxidant activity on nuclear factor kappaB
      (NF-kappaB) binding activity and DNA integrity in HepG2 cells. Gel mobility shift
      assays using a gamma-32P-labelled NF-kappaB oligonucleotide probe showed that
      treatment of HepG2 cells with quercetin (up to 10 microM, sub-cytotoxic) did not
      elevate NF-kappaB binding activity of nuclear extract protein but did inhibit
      binding activity of an extract from cells treated with the oxidant H2O2. A
      similar inhibition by quercetin of H2O2-induced NF-kappaB transcriptional
      activation was demonstrated using a cat reporter gene assay. Considering
      oxidative DNA damage, using single cell gel electrophoresis (comet) assay we have
      demonstrated that quercetin (10 microM and below) did not induce DNA strand
      breaks. However, a marked and statistically significant (P < 0.01 at 10 microM)
      inhibition of strand breakage produced by H2O2 was detected. The specific
      formation of 8-oxo-2'-deoxyguanosine (8-oxodG) in calf thymus DNA exposed to
      either gamma-irradiation or the Fenton reaction system was also inhibited (P <
      0.01 at 10 microM) by quercetin in a dose-dependent manner. This was not
      accompanied by formation of 8-oxodG by quercetin itself. The inhibition of 8
      oxodG formation by gamma-irradiation was more potent (IC50 = 0.05 microM) than
      that by the Fenton reaction (IC50 = 0.5 microM), implying that the mechanism of
      protection may be different between the two systems. The inhibition of both NF
      kappaB binding activity and oxidative DNA damage suggests that its antioxidant
      potential outweighs its oxidative potential in a cellular environment, which may
      contribute to anticarcinogenic and anti-inflammatory effects.

PMID- 9771929
TI  - Zinc replenishment reduces esophageal cell proliferation and N
      nitrosomethylbenzylamine (NMBA)-induced esophageal tumor incidence in zinc
      deficient rats.
AB  - Previous work has shown that sustained increased and decreased cell
      proliferation, induced by dietary zinc deficiency and caloric restriction
      respectively, influence the course of N-nitrosomethylbenzylamine (NMBA)-induced
      esophageal carcinogenesis in rats. The present study considered whether the
      increased cell proliferation and esophageal tumor incidence induced by zinc
      deficiency are reversed upon zinc replenishment. Weanling rats were maintained
      initially on a deficient diet containing 4 p.p.m. zinc. After 5 weeks, carcinogen
      treated animals were given six intragastric doses of NMBA (2 mg/kg twice weekly).
      Controls were untreated. After the second NMBA dose, the rats were divided into
      three dietary groups. One group was continued on the deficient diet, while the
      other two groups were switched to diets containing either 75 or 200 p.p.m. zinc,
      with half of the members in each group fed ad libitum and half pair-fed with
      deficient rats. NMBA-untreated controls were similarly replenished. At various
      time points, esophageal cell proliferation was assessed in five animals from each
      group by immunohistochemical detection of cells in S phase, with in vivo 5-bromo
      2'deoxyuridine labeling. At 11 weeks after the first dose, esophageal tumor
      incidence was greatly reduced, from 100% in the deficient group to 26 and 14%
      respectively in the replenished groups fed ad libitum 75 and 200 p.p.m. zinc and
      to 14 and 11% respectively in the replenished groups pair-fed 75 and 200 p.p.m.
      zinc. In addition, the number of tumors per esophagus was reduced from 9.93 +/-
      4.25 in deficient rats, to a range of 0.11 +/- 0.31-0.30 +/- 0.54 in replenished
      animals. Following zinc replenishment, esophageal cell proliferation, as measured
      by labeling index (LI), the number of labeled cells and the total number of
      cells, was markedly decreased in NMBA-untreated and -treated esophagi as compared
      with those in corresponding deficient esophagi. Thus, the esophageal cell
      proliferation induced by zinc deficiency is reversed by zinc replenishment and
      replenished animals have a markedly lower incidence of esophageal tumors.

PMID- 9771930
TI  - Effects of dietary fat and a vegetable-fruit mixture on the development of
      intestinal neoplasia in the ApcMin mouse.
AB  - The variation in colorectal cancer (CRC) incidence worldwide strongly suggests a
      role for dietary influences. Based on epidemiological data, protective effects of
      vegetables and fruit intake on CRC are widely claimed, while other data indicate
      a possible increased CRC risk from (higher) dietary fat intake. Therefore, we
      have investigated single and interactive effects of dietary fat and a vegetable
      fruit mixture (VFM) in the ApcMin mouse, a mouse model for multiple intestinal
      neoplasia. In this study, four different diets (A-D) were compared, which were
      either low in fat (20% energy diets A/B) or high in fat (40% energy diets C/D).
      In addition, 19.5% (wt/wt) of the carbohydrates in diets B and D were replaced by
      a freeze-dried VFM. The diets were balanced so that they only differed among each
      other in fat/carbohydrate content and the presence of specific plant
      constituents. Because the initiation of intestinal tumors in ApcMin mice occurs
      relatively early in life, exposure to the diets was started in utero. Without the
      addition of VFM, mice maintained at a high-fat diet did not develop significantly
      higher numbers of small or large intestinal adenomas than mice maintained at a
      low-fat diet. VFM added to a low-fat diet significantly lowered multiplicity of
      small intestinal polyps (from 16.2 to 10.2/mouse, 15 animals/group), but not of
      colon tumors in male ApcMin mice only. Strikingly, addition of VFM to female mice
      maintained on a low-fat diet and to both sexes maintained on a high-fat diet
      significantly enhanced intestinal polyp multiplicity (from 16.5 to 26.7
      polyps/mouse). In conclusion, our results indicate that neither a lower fat
      intake nor consumption of VFM included in a high-fat diet decreases the
      development of polyps in mice genetically predisposed to intestinal tumor
      development.

PMID- 9771931
TI  - Synthesis and excretion profile of 1,4-[14C]phenylenebis(methylene)selenocyanate
      in the rat.
AB  - 1,4-Phenylenebis(methylene)selenocyanate (p-XSC) inhibits chemically induced
      tumors in several laboratory animal models. To understand its mode of action, we
      synthesized p-[14C]XSC, examined its excretion pattern in female CD rats and also
      the nature of its metabolites. p-[14C]XSC was synthesized from alpha,alpha
      dibromo-p-[ring-14C]xylene in 80% yield. The excretion profile of p-[14C]XSC
      (15.8 mg/kg body wt, 200 microCi/rat, oral administration, in 1 ml corn oil) in
      vivo was monitored by measuring radioactivity and selenium content. On the basis
      of radioactivity, approximately 20% of the dose was excreted in the urine and 68%
      in the feces over 3 days. The cumulative percentages of the dose excreted over 7
      days were 24% in urine and 75% in feces, similar to excretion rates of selenium.
      According to selenium measurement, <1% of the dose was detected in exhaled air;
      radioactivity was not detected. Only 15% of the dose was extractable from the
      feces with EtOAc and was identified as tetraselenocyclophane (TSC). Most of the
      radioactivity remained tightly bound to the feces. Approximately 10% of this
      bound material converted to TSC on reduction with NaBH4. Organic soluble
      metabolites in urine did not exceed 2% of the dose; sulfate (9 % of urinary
      metabolites) and glucuronic acid (19.5% of urinary metabolites) conjugates were
      observed but their structural identification is still underway. Co-chromatography
      with a synthetic standard led to the detection of terephthalic acid (1,4
      benzenedicarboxylic acid) as a minor metabolite. The major urinary conjugates
      contained selenium. Despite the low levels of selenium in the exhaled air, the
      reductive metabolism of p-XSC to H2Se cannot be ruled out. Identification of TSC
      in vivo indicates that a selenol may be a key intermediate responsible for the
      chemopreventive action of p-XSC.

PMID- 9771932
TI  - Identification of dithiolethiones with better chemopreventive properties than
      oltipraz.
AB  - Oltipraz and related dithiolethiones are an important class of chemopreventive
      agents. Studies were undertaken to identify cancer chemopreventive
      dithiolethiones more active than oltipraz. Largely based upon enzyme induction
      activities in vitro, 17 dithiolethiones, including oltipraz, were analyzed for
      their ability to induce hepatic phase II enzyme activities in vivo. Of these
      compounds, 15 produced greater induction of NAD(P)H:quinone reductase and 11
      yielded greater induction of glutathione S-transferase than oltipraz. All 17
      dithiolethiones were then tested for their ability to inhibit acute
      hepatotoxicity by aflatoxin B1 (AFB1), which previously has been shown to be an
      intermediate predictor of chemopreventive activity. Rats were pretreated with
      dithiolethiones (0.3 mmol/kg body wt, three times a week per os) and challenged
      with two acutely toxic doses of AFB1 (0.5 mg/kg body wt, once daily for two
      successive days per os). Inhibition of hepatotoxicity was measured by changes in
      body weight gain during AFB1 challenge, reduction in levels of hepatic enzymes in
      serum and diminution of bile duct cell proliferation. Nine dithiolethiones
      spanning a range of responses in this toxicity screen were further tested for
      their ability to prevent AFB1-induced tumorigenicity, as assessed by a reduction
      in hepatic burden of putative preneoplastic foci. Six dithiolethiones were found
      to be considerably more effective than oltipraz in preventing AFB1-induced
      tumorigenesis. In general, dithiolethiones that were very effective in inhibition
      of acute hepatotoxicity were also found to be effective in prevention of hepatic
      tumorigenesis.

PMID- 9771933
TI  - Lack of a co-promoting effect of a 60 Hz magnetic field on skin tumorigenesis in
      SENCAR mice.
AB  - It has been proposed that extremely low frequency (ELF) magnetic fields may
      enhance tumorigenesis through a co-promotional mechanism. This hypothesis has
      been further tested using the two-stage model of mouse skin carcinogenesis, i.e.
      12-O-tetradecanoylphorbol-13-acetate (TPA)-induced promotion of skin tumors in
      mice initiated by a single subcarcinogenic dose of 7,12
      dimethylbenz[a]anthracene. Experimentation described herein utilized the SENCAR
      mouse and examined the effect of a magnetic field on skin tumor promotion induced
      by three different doses of TPA within its dose-response range, i.e. 0.85, 1.70
      or 3.40 nmol, administered twice per week. SENCAR mice (56/treatment group) were
      exposed to a 60 Hz magnetic field having a flux density of 2 mT for 6 h/day for 5
      days/week and compared with mice exposed to the ambient magnetic field. Tumor
      incidence and multiplicity were monitored weekly for 23 weeks of TPA promotion.
      Statistical evaluation of the effects of the magnetic field on tumor incidence
      and multiplicity did not reveal any statistically significant effects; thus,
      within the sensitivity limits imposed by the animal model and the exposure
      parameters employed, no promotional or co-promotional effect of a 2 mT magnetic
      field on skin tumor development in SENCAR mice could be demonstrated.

PMID- 9771934
TI  - Prenatal TCDD and predisposition to mammary cancer in the rat.
AB  - Prenatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was investigated
      for its potential to predispose to breast cancer. Analysis of mammary gland
      differentiation and cell proliferation were used as biomarkers. Timed pregnant
      Sprague-Dawley CD rats were gavaged with 1 microg TCDD/kg on day 15 post
      conception. Control animals were treated with the same volume of vehicle (sesame
      oil) on the same schedule. Mammary gland differentiation studies revealed that
      prenatal TCDD treatment, as compared with sesame oil treatment, resulted in
      significantly more terminal end buds and fewer lobules II in 50-day-old
      offspring, but no significant alterations to mammary gland differentiation in 21
      day-old offspring. Terminal end buds are the most susceptible terminal ductal
      structures and lobules the least susceptible to carcinogenesis. Prenatal TCDD
      treatment did not alter labeling index in the mammary terminal ductal structures
      of 21- and 50-day-old rats, but the total proliferative compartment in terminal
      end buds of 50-day-old rats was larger. Prenatal TCDD treatment resulted in an
      increased number of chemically induced mammary adenocarcinomas in rats. TCDD
      delayed time of vaginal opening and caused disruption to the estrous cycle.
      Alteration to mammary gland differentiation (increased number of terminal end
      buds) is correlated with increased susceptibility to mammary cancer from prenatal
      exposure to TCDD.

PMID- 9771935
TI  - Aryl hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of
      diindolylmethane.
AB  - Phytochemicals such as indole-3-carbinol (I3C) and sulforaphane are components of
      cruciferous vegetables which exhibit antitumorigenic activity associated with
      altered carcinogen metabolism and detoxification. Diindolylmethane (DIM) is a
      major acid-catalyzed metabolite of I3C formed in the gut that binds to the aryl
      hydrocarbon receptor (AhR) and treatment of MCF-7 human breast cancer cells with
      10-50 microM DIM resulted in rapid formation of the nuclear AhR complex and
      induction of CYP1A1 gene expression was observed at concentrations >50 microM.
      Previous studies have demonstrated that 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD), a high affinity AhR ligand, inhibits 17beta-estradiol (E2)-induced
      responses in MCF-7 cells and growth of E2-dependent 7,12-dimethylbenzanthracene
      (DMBA)-induced mammary tumors in female Sprague-Dawley rats. Results of this
      study show that like TCDD, DIM inhibits E2-induced proliferation of MCF-7 cells,
      reporter gene activity in cells transiently transfected with an E2-responsive
      plasmid (containing a frog vitellogenin A2 gene promoter insert) and down
      regulates the nuclear estrogen receptor. Moreover, DIM (5 mg/kg every other day)
      also inhibits DMBA-induced mammary tumor growth in Sprague-Dawley rats and this
      was not accompanied by induction of hepatic CYP1A1-dependent activity. Thus, DIM
      represents a new class of relatively non-toxic AhR-based antiestrogens that
      inhibit E2-dependent tumor growth in rodents and current studies are focused on
      development of analogs for clinical treatment of breast cancer.

PMID- 9771936
TI  - Dibenzo[a,l]pyrene (dibenzo[def,p]chrysene): fjord-region distortions.
AB  - The molecular dimensions of the potent chemical carcinogen
      dibenzo[def,p]chrysene, also known as dibenzo[a,l]pyrene, have been determined by
      X-ray diffraction methods. This analysis shows that the molecule is considerably
      distorted so that it is non-planar with an angle of 27.6 degrees between the
      outermost rings and a widening of C-C-C bond angles in the fjord region. The
      dimensions of the molecular distortion due to atomic overcrowding in the fjord
      region are presented. This polycyclic aromatic hydrocarbon is a more potent
      carcinogen than is benzo[a]pyrene or its 11-methyl derivative. Comparisons of the
      distortions in dibenzo[a,l]pyrene with the geometries of various other polycyclic
      aromatic hydrocarbons containing fjord- or bay-region methyl groups provide
      structural data on the ratio of angular to torsional distortion in such
      overcrowded molecules.

PMID- 9771937
TI  - Exposure to 60 Hz magnetic fields and risk of lymphoma in PIM transgenic and TSG
      p53 (p53 knockout) mice.
AB  - The results of a number of epidemiology studies suggest that exposure to power
      frequency (50 and 60 Hz) magnetic fields may be a risk factor for hematopoietic
      neoplasia. To generate experimental data to test this hypothesis, the influence
      of magnetic field exposure on lymphoma induction was determined in two strains of
      mice that are genetically predisposed to the disease. PIM mice, which carry the
      pim-1 oncogene, are highly sensitive to lymphoma induction by N-ethyl-N
      nitrosourea (ENU); ENU-treated PIM mice were studied as a 'high incidence'
      lymphoma model. TSG-p53 (p53 knockout) mice, in which the p53 tumor suppressor
      gene has been deleted from the germ line, develop lymphoma as an age-related
      change; hemizygous TSG-p53 mice were studied as a 'low incidence' lymphoma model.
      Beginning 1 day after a single i.p. injection of 25 mg ENU/kg body wt, groups of
      30 PIM mice/sex were exposed for 18.5 h/day to pure, linearly polarized,
      transient-free 60 Hz magnetic fields at field strengths of 0 (sham control),
      0.02, 2.0 or 10.0 Gauss (G). An additional group of 30 PIM mice/sex was exposed
      intermittently (1 h on, 1 h off) to 10.0 G fields. Groups of 30 TSG-p53 mice/sex
      were exposed continuously to magnetic field strengths of 0 (sham control) or 10.0
      G; TSG-p53 mice received no ENU. Studies were terminated after 23 weeks of
      magnetic field exposure. Lymphoma incidence in male PIM mice exposed continuously
      to 10.0 G magnetic fields was significantly reduced from that seen in sex-matched
      sham controls; survival, lymphoma incidence and lymphoma latency in other groups
      of PIM mice did not differ from sham controls. Survival and lymphoma incidence in
      all groups of TSG-p53 mice was 7% or less, regardless of magnetic field exposure
      regimen. These data do not support the hypothesis that exposure to magnetic
      fields is a significant risk factor for lymphoid neoplasia in mice with a genetic
      predisposition to the disease.

PMID- 9771938
TI  - Increased tumors but uncompromised fertility in the female descendants of mice
      exposed developmentally to diethylstilbestrol.
AB  - Prenatal exposure to diethylstilbestrol (DES) has been associated with the
      subsequent development of reproductive tract abnormalities, including poor
      reproductive outcome and neoplasia, in experimental animals and humans.
      Experimental animal studies with chemical carcinogens have raised the possibility
      that adverse effects of DES may be transmitted to succeeding generations. To
      evaluate this possibility and to determine if there is a sensitive window of
      developmental exposure, outbred CD-1 mice were treated with DES during three
      stages of development: group 1 was treated on days 9-16 of gestation (2.5, 5 or
      10 microg/kg maternal body wt), the time of major organogenesis; group II was
      treated once on day 18 of gestation (1000 microg/kg maternal body wt) just prior
      to birth; group III was treated on days 1-5 of neonatal life (0.002
      microg/pup/day). Female mice (F1) in each group were raised to sexual maturity
      and bred to control males. As previously reported, fertility of the F1 DES
      exposed females was decreased in all groups. Female offspring (DES lineage or F2)
      from these matings were raised to maturity and housed with control males for 20
      weeks. The fertility of these DES lineage female mice was not affected by DES
      exposure of their 'grandmothers'. DES lineage mice were killed at 17-19 and 22-24
      months of age. An increased incidence of malignant reproductive tract tumors,
      including uterine adenocarcinoma, was seen in DES lineage mice but not in
      corresponding controls; the range and prevalence of tumors increased with age.
      Because uterine adenocarcinomas were seen in all three DES groups, all
      developmental exposure periods were considered susceptible to the adverse effects
      of DES. These data suggest that the reduced fertility observed in the DES F1
      female mice was not transmitted to their descendants; however, increased
      susceptibility to tumor formation is apparently transmitted to subsequent
      generations.

PMID- 9771939
TI  - Weak electrophile selective characteristics of the rat preneoplastic marker
      enzyme glutathione S-transferase P-form, GST-P (7-7): a theory of linear free
      energy relationships for evaluation of the active site hydrophobicity of
      isoenzymes.
AB  - Subsite (the H-site) hydrophobicity of the rat glutathione S-transferase P-form
      (GST-P, 7-7, pi class species) and six other GST species of the alpha and mu
      classes was examined theoretically and experimentally by application of linear
      free energy relationships (LFERs) with a series of S-alkylated glutathiones,
      GS(CH2)n-1CH3 (n = 1-12). Plots of log Ki (inhibition constant) versus n were
      used to generate LFERs for microscopic hydrophobic interactions. The free
      enthalpic change per methylene group (-deltadeltaG degrees, absolute value)
      evaluated for GST-P (1.8 kJ/mol) was lower than those for the other six forms
      (2.4-3.5 kJ/mol). In addition, the enthalpic change (deltadeltaH degrees)
      determined from van't Hoff plots was much smaller for GST-P (0.5 kJ/mol) than the
      GST1-1 value (5.9 kJ/mol). As these thermodynamic parameters, deltadeltaG degrees
      and deltadeltaH degrees, may be considered as indirect and direct measures of GST
      hydrophobicity respectively, the H-site hydrophobicity of GST-P is thus very low
      as compared with those of other forms, clearly indicating that the pi class GST-P
      selectively targets for weak electrophiles, i.e. water-soluble carcinogens such
      as acrolein and hydroxyalkenals. The finding also defines a host-defensive role
      of the preneoplastic cells against the carcinogenic insult, although paradoxical.

PMID- 9771940
TI  - Rearrangements in minisatellite sequences induced by aflatoxin B1 in a
      metabolically competent strain of Saccharomyces cerevisiae.
AB  - The role of aflatoxin B1 (AFB1) in the induction of rearrangements affecting
      minisatellite sequences was studied in an in vitro yeast model. The Saccharomyces
      cerevisiae strain used expresses human cytochrome P450 1A2 and NADPH-cytochrome
      P450 oxidoreductase and has previously been used to study genetic recombination
      events induced by AFB1. DNA multilocus fingerprinting was performed using probe
      M13 core hybridizing to a set of hypervariable minisatellite sequences in S.
      cerevisiae. Frequent spontaneous genomic alterations that affect the
      minisatellite fingerprint pattern were observed. Control cultures showed 15.8%
      rearrangements in minisatellites, and this frequency increased to 40.0% in
      cultures exposed to AFB1 (80 microg/ml). A total of approximately 29
      minisatellite loci were visualized for each culture. Given the number of cultures
      examined (40 AFB1-treated and 38 controls) the rearrangement frequency per
      detectable minisatellite was 2.59% in the AFB1-treated group and 0.73% in the
      control group, which represents a statistically significant (P = 0.001)
      difference. Thus, our data strongly suggest that AFB1 can promote the genetic
      events responsible for minisatellite rearrangements in the yeast genome. Such
      genetic rearrangements may be important events during the etiology of liver
      carcinogenesis in people chronically exposed to dietary aflatoxins.

PMID- 9771941
TI  - Aberrant crypt focus promotion and glucose intolerance: correlation in the rat
      across diets differing in fat, n-3 fatty acids and energy.
AB  - McKeown-Eyssen (Cancer Epidemiol. Biomarkers Prevent., 3, 687-695, 1994) and
      Giovannucci (Cancer Causes Control, 6, 164-179, 1995), noting the striking
      similarity in lifestyle risk factors for colorectal cancer and insulin
      resistance, proposed that the hyperinsulinemia, glycemia and hypertriglyceridemia
      associated with insulin resistance promotes colon cancer. To compare the effect
      of diet on colon cancer promotion and insulin resistance in the F344 rat, we
      assessed the effect of fat, n-3 fatty acids and energy in pairwise comparisons on
      average size of aberrant crypt foci (ACF) and on glucose intolerance in the same
      animals in a single experiment. Diets high in fat and energy increased and diets
      with increased n-3 fatty acids and calorie restriction decreased both ACF growth
      and glucose intolerance compared with control diets. The measures of promotion of
      colon cancer and insulin resistance were strongly correlated (n = 98, r = 0.67, P
      < 0.001). In addition, both were highly correlated with daily energy intake (r =
      0.62 and 0.66) and were also correlated with basal (post-prandial) insulin,
      glucose and triglycerides (r = 0.31-0.53, P < 0.01). We concluded that ACF growth
      and glucose intolerance are correlated for a wide range of diets and that
      increased circulating energy (glucose and triglycerides) may lead to both colon
      cancer promotion and insulin resistance.

PMID- 9771942
TI  - Specificities of human glutathione S-transferase isozymes toward anti-diol
      epoxides of methylchrysenes.
AB  - The specificities of human glutathione (GSH) S-transferase (GST) isozymes of
      class alpha (hGSTA1-1), mu (hGSTM1-1) and pi (hGSTP1-1), including the three
      allelic forms of hGSTP1-1 [hGSTP1-1(I104,A113), hGSTP1-1(V104,A113) and hGSTP1
      1(V104,V113)], in catalyzing the GSH conjugation of anti-diol epoxide
      stereoisomers of 5-methylchrysene (anti-5-MeCDE) have been examined. The specific
      activities of human GSTs were significantly higher toward (+)-anti-5-MeCDE than
      toward the (-)-enantiomer of anti-5-MeCDE. All three variants of hGSTP1-1 were
      significantly more efficient than either hGSTA1-1 or hGSTM1-1 in GSH conjugation
      of (+)-anti-5-MeCDE. The catalytic efficiencies of hGSTP1-1 variants toward (+)
      anti-5-MeCDE were in the order hGSTP1-1(I104,A113) > hGSTP1-1(V104,V113) > hGSTP1
      1(V104,A113). The present study suggests that the I104,A113 allele, which is most
      frequent in human populations, may play a major role in the detoxification of (+)
      anti-5-MeCDE. This may point to specificity, because previous studies from our
      laboratory have shown that the hGSTP1-1(V104,V113) isoform is significantly more
      efficient than the other two variants of hGSTP1-1 in catalyzing GSH conjugation
      of (+)-anti-7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)
      anti-BPDE], the ultimate carcinogen of benzo[a]pyrene. Even though the mechanism
      of the differences in the activities of hGSTP1-1 variants toward anti-5-MeCDE
      versus anti-BPDE remains to be elucidated, it seems that the molecular
      configuration of the diol epoxide is an important determinant of the activity of
      hGSTP1-1 isoforms toward polycyclic aromatic hydrocarbon diol epoxides.

PMID- 9771943
TI  - Decreased levels of p26-Bcl-2, but not p30 phosphorylated Bcl-2, precede TGFbeta1
      induced apoptosis in colorectal adenoma cells.
AB  - Bcl-2 expression is confined to the base of the colonic crypt, whereas
      transforming growth factor beta (TGFbeta) is expressed in the upper crypt, as are
      the apoptotic death promoters, Bak and Bax. In colonic adenoma cells, TGFbeta
      induces a growth arrest. In some adenoma cell lines, this is accompanied by
      apoptosis and in others it is not. In this study, we used two human colonic
      adenoma cell lines: RG/C2, in which TGFbeta induces a G1 arrest without
      apoptosis, and BH/C1, in which TGFbeta induces both a G1 arrest and apoptosis.
      TGFbeta does not induce apoptosis in RG/C2 cells even if hydrocortisone and
      insulin are removed from the culture medium. In BH/C1 cells, TGFbeta induces
      apoptosis in the presence of insulin and hydrocortisone. Apoptosis induced by
      TGFbeta is preceded by a reduction in p26-Bcl-2 protein levels. There was no
      change in the levels of the p30 phosphorylated form of Bcl-2 or in levels of the
      proapoptotic proteins Bax or Bak. RG/C2 cells did not show decreased Bcl-2 levels
      in response to TGFbeta-induced growth inhibition. Therefore, TGFbeta regulates
      Bcl-2 expression in colonic adenoma cells which undergo apoptosis in response to
      TGFbeta, but not in those which are growth inhibited, but resistant to TGFbeta
      induced apoptosis. TGFbeta may play an important role in the colonic epithelium,
      not only in the inhibition of cell proliferation, but also in the regulation of
      apoptosis.

PMID- 9771944
TI  - Effect of dietary curcumin and dibenzoylmethane on formation of 7,12
      dimethylbenz[a]anthracene-induced mammary tumors and lymphomas/leukemias in
      Sencar mice.
AB  - Female Sencar mice (6 weeks old) were administered 1 mg of 7,12
      dimethylbenz[a]anthracene (DMBA) by oral gavage once a week for 5 weeks. At 20
      weeks after the first dose of DMBA, 68% of mice developed mammary tumors (the
      average 1.08 tumors per mouse) and 45% had lymphomas/leukemias. Feeding 1%
      dibenzoylmethane (DBM) in AIN 76A diet, starting at 2 weeks before the first dose
      of DMBA and continuing until the end of the experiment, inhibited both the
      multiplicity and incidence of DMBA-induced mammary tumor by 97%. The incidence of
      lymphomas/leukemias was completely inhibited by 1% DBM diet. In contrast, feeding
      2% curcumin diet had little or no effect on the incidence of mammary tumors, and
      the incidence of lymphomas/leukemias was reduced by 53%.

PMID- 9771945
TI  - Recovery of the normal p53 response after UV treatment in DNA repair-deficient
      fibroblasts by retroviral-mediated correction with the XPD gene.
AB  - Among the major responses of human cells to DNA damage is accumulation of the p53
      tumor suppressor protein, which plays a crucial role as a cell-cycle checkpoint.
      We have already shown that this response is different in cells from the UV
      hypersensitive human syndromes xeroderma pigmentosum (XP) and trichothiodystrophy
      (TTD), which overlap with each other and arise from mutations in genes involved
      in nucleotide excision repair. In this paper we report that correction of the
      repair defect by retroviral-mediated transduction of the wild-type XPD gene in XP
      D and TTD/XP-D untransformed primary fibroblasts leads to a normal p53 response
      in these cells. Thus, the complemented cells, like normal human fibroblasts,
      require higher UV doses (10 J/m2) for p53 induction than the parental repair
      deficient XP-D or TTD/XP-D cells (both mapping at the XPD locus), which
      accumulate p53 protein at very low UV doses (2.5 and 5 J/m2). The p53 protein
      levels return to normal 24 h after irradiation when UV-induced lesions have been
      efficiently repaired by the restored NER activity. These data confirm our earlier
      results that p53 accumulation following UV treatment is directly related to the
      presence of unrepaired cyclobutane dimers on the transcribed strand of active
      genes.

PMID- 9771946
TI  - Re: Hunter, D.J., Hankinson, S.E., Hough, H. et al. (1997), A prospective study
      of NAT2 acetylation genotype, cigarette smoking and risk of breast cancer.
      Carcinogenesis, 18, 2127-2132.

PMID- 9771947
TI  - Yeast cells expressing differential levels of human or yeast DNA topoisomerase
      II: a potent tool for identification and characterization of topoisomerase II
      targeting antitumour agents.
AB  - PURPOSE: To identify and characterize the specificity and potency of
      topoisomerase II-interacting antitumour drugs in an in vivo model utilizing the
      yeast Saccharomyces cerevisiae. METHODS: Four yeast transformants were selected
      for the expression of either human or yeast DNA topoisomerase II at different,
      biologically relevant, levels under the tight control of promoters of various
      strengths. RESULTS: Analyses of 24 drugs permitted their classification into
      three distinct groups, depending on whether they induced topoisomerase II-related
      cytotoxicity (etoposide), showed nonspecific cytotoxicity (camptothecin), or
      exerted no cytotoxicity at all (vinorelbine). Within the first group different
      patterns of action were distinguishable: (1) classical topoisomerase II
      expression-dependent cytotoxicity for both species of enzyme (e.g. etoposide,
      amsacrine, doxorubicin, actinomycin D), although amsacrine and TOP 53 were more
      active, respectively, on human and yeast topoisomerase II; and (2) compounds that
      appeared to poison only one species of topoisomerase II with, for example,
      genistein and the bisdioxopiperazine ICRF-193 lethally targeting only the human
      type, and mitoxantrone only the yeast isozyme. Three of the 16 known
      topoisomerase II inhibitors tested were not correctly identified with this assay,
      possibly owing to restricted cell wall permeability or to the absence of correct
      processing pathways such as, for example, in the case of the prodrug etopophos.
      CONCLUSION: This methodology, in vivo in yeast, selected for a large range of
      potent topoisomerase II-targeting anticancer agents. Of particular interest in
      this yeast model, and in contrast to yeast topoisomerase II, human topoisomerase
      II was shown to confer dominant sensitivity in the presence of the series of
      bisdioxopiperazine derivatives tested. This assay therefore has the potential
      easily to identify and characterize the potency and specificity of synthesized
      anticancer drugs with modified original chemical structures or those present, for
      example, in natural plant extracts or marine organisms.

PMID- 9771948
TI  - Mechanism and pharmacological specificity of dUTPase-mediated protection from DNA
      damage and cytotoxicity in human tumor cells.
AB  - PURPOSE: We have reported previously that the expression of E. coli dUTPase
      (dutE) can protect HT29 cells from 5-fluorodeoxyuridine (FdUrd)-induced DNA
      fragmentation and cytotoxicity. In the study reported here, we further
      characterized the ability of dutE expression in one HT29 clone, dutE7, to alter
      the effects of treatment with FdUrd and other thymidylate synthase (TS)
      inhibitors. In addition, we developed two HuTu80 dutE-expressing clones using a
      pLNCX-dutE retroviral construct and tested their sensitivity to FdUrd-induced DNA
      fragmentation and cytotoxicity. METHODS: Both a dutE retroviral expression system
      and a dutE antibody were developed to facilitate the generation and screening of
      dutE-expressing clones. HT29 and HuTu80 clones expressing dutE were tested for
      drug-induced DNA damage with either alkaline elution or pulsed field gel
      electrophoresis and drug-induced loss of clonogenicity. RESULTS: Following a 24-h
      treatment with 100 microM CB3717 or 500 nM methotrexate (MTX), dutE7 cells were
      significantly less sensitive to drug-induced loss of clonogenicity than con3
      cells. DutE7 cells were also resistant to CB3717-induced DNA fragmentation at 24
      h. However, following a 48-h treatment with CB3717 or MTX there was no difference
      in survival between con3 and dutE7 cells, even though DNA damage was still
      greatly attenuated in the dutE7 cell line. In addition, expression of dutE in two
      HuTu80 clones, 80 C and 80 K, did not protect these cells from FdUrd-induced DNA
      damage or cytotoxicity. CONCLUSIONS: We conclude that the role of uracil
      misincorporation and subsequent DNA damage in cytotoxicity induced by TS
      inhibitors, in HT29 cells, is time dependent, and that cytotoxicity caused by
      long-term exposure to these drugs is largely independent of resultant DNA damage,
      in this cell line. The inability of dutE to protect HuTu80 cells from FdUrd
      further suggests that the significance of uracil misincorporation resulting from
      TS inhibition varies among cell lines.

PMID- 9771949
TI  - Pharmacokinetic analysis of high-dose toremifene in combination with doxorubicin.
AB  - PURPOSE: Toremifene (Fareston) is an orally administered triphenylethylene
      derivative with chemosensitizing activity in vitro in estrogen receptor-negative
      multidrug-resistant human breast cancer cells. The purpose of this study was to
      evaluate the effects of high-dose toremifene (600 mg/day for 5 days) on the
      plasma pharmacokinetics of doxorubicin in humans. The 600-mg dose had been
      previously established as the maximum tolerated dose in a phase I study of 35
      patients. METHODS: Doxorubicin was administered as an intravenous (i.v.) bolus
      over 15 min at a dose of 60 mg/m2 to 11 patients in the absence of toremifene
      pretreatment to establish baseline doxorubicin pharmacokinetics. Six of these
      patients received 600 mg/day toremifene for 5 days 4 weeks later, followed by an
      i.v. bolus dose of doxorubicin (60 mg/m2) on day 5. During toremifene pre
      treatment, blood specimens (5 ml) were drawn at 0, 2, 4, and 24 h after dosing to
      assess peak levels. Following doxorubicin administration in each cycle, blood
      specimens were collected over a 72-h period for determination of the terminal
      half-life of elimination. Plasma concentrations of doxorubicin and toremifene
      were assessed by high-performance liquid chromatography (HPLC). Cumulative linear
      areas under the time-concentration curve (AUC) for doxorubicin were calculated
      using a noncompartmental model. RESULTS: Prior to toremifene dosing, baseline
      doxorubicin pharmacokinetic studies showed an average terminal half-life of
      elimination of 40.04+/-7.86 h in 4 patients, and an average AUC of 135 600+/-67
      600 microg/ml.h in 11 patients. In 4 of the patients receiving 600 mg/day
      toremifene for 5 days, the average terminal half-life of elimination was 38.12+/
      7.81 h, and the average AUC was 141 900+/-62 900 microg/ml.h in 6 patients, i.e.
      a slight increase of 4.6%. No statistically significant change in the doxorubicin
      elimination kinetics with or without toremifene therapy was observed.
      CONCLUSIONS: Toremifene does not appear to interfere with the elimination
      kinetics of doxorubicin.

PMID- 9771950
TI  - Prophylactic intravesical instillation chemotherapy against recurrence after a
      transurethral resection of superficial bladder cancer: a randomized controlled
      trial of doxorubicin plus verapamil versus doxorubicin alone. The Kyushu
      University Urological Oncology Group.
AB  - PURPOSE: We investigated whether verapamil (VR), a known chemosensitizing agent
      of P-glycoprotein-mediated multidrug resistance, could enhance the preventative
      effect of doxorubicin (Adriamycin, ADM) on both intravesical recurrence and
      disease progression after transurethral resection (TUR) of superficial bladder
      cancer. METHODS: The patients were randomized into two groups: one group received
      an intravesical instillation of ADM (30 mg) plus VR (15 mg) after TUR of
      superficial bladder cancer (19 times over 1 year), and the other group received
      ADM alone on the same treatment schedule. The nonrecurrence rate, the incidence
      of disease progression at the first recurrence and the side effects were compared
      over a median follow-up of 38.5 months. RESULTS: Of the 226 patients registered,
      157 were evaluable. No significant differences were observed in the patients'
      characteristics between the two groups. Although the incidence of disease
      progression at the first recurrence was not significantly different between the
      two groups, the ADM plus VR instillation group did show a significantly higher
      nonrecurrence rate than the ADM-only instillation group, and such significance
      persisted even when any possible bias was allowed for in a multivariate analysis.
      In terms of side effects, the incidence and severity of bladder irritation
      symptoms were not significantly different between the two groups. CONCLUSIONS:
      Intravesical instillation chemotherapy with ADM plus VR was found to have a
      significantly greater beneficial effect than with ADM alone for preventing
      recurrence after TUR of superficial bladder cancer.

PMID- 9771952
TI  - Pharmacokinetics and tissue distribution of the imidazoacridinone C1311 in tumour
      bearing mice.
AB  - C1311 is the most active member of a new series of rationally designed anti
      cancer agents, the imidazoacridinones, which has shown promising pre-clinical
      anti-tumour activity in vitro and in vivo against a variety of human colon
      cancers and is a strong candidate for clinical trials. Data are not available on
      the pharmacokinetic properties of this compound; therefore, the main aim of this
      project was to study the plasma pharmacokinetics and tissue and tumour
      distribution of C1311 in mice and to assess, prior to potential clinical
      application, whether these pharmacokinetics were linear with respect to the dose.
      The distribution of C1311 in whole blood was also studied. NMRI or NCR-Nu mice
      were used throughout the study. C1311 was given i.p. at doses of 15, 50, 100 and
      (the maximum tolerated dose, (MTD) 150 mg kg(-l) i.p. Plasma, tissue and tumour
      levels were monitored over a 24-h period using high-performance liquid
      chromatography (HPLC) with fluorescence detection. The distribution of C1311 in
      murine and human whole blood was studied using both HPLC and fluorescence
      microscopy. C1311 was quickly cleared from the plasma (47410 ml min kg(-1)) and
      rapidly distributed into the tissues at all doses. Tissue-to-plasma ratios were
      large, ranging from 8 in the liver (15 mg kg(-l)) to 600 (50 mg kg(-1)) in the
      spleen. Overall concentrations were ranked in the order of plasma << liver <
      kidney < fat < small intestine < spleen. Tumour concentrations were similar to
      those measured in the liver and kidney, with AUCs being 186 (MAC15A) and 94.4
      microg h ml(-l)(HT-29). Plasma pharmacokinetics were linear at doses of 15-100 mg
      kg(-1), but disproportionate increases were seen in plasma and tissue
      concentrations at doses above 100 mg kg(-l). C1311 distributed unevenly in both
      mouse and human blood, with higher concentrations occurring in the cellular
      fraction than in plasma. Nucleated cells accounted for a large proportion of this
      localised drug. In conclusion, C1311 is quickly cleared from the plasma and
      rapidly distributed into the tissues, with tissue concentrations being far higher
      than plasma levels. The plasma pharmacokinetics are linear up to but not above
      doses of 100 mg kg(-1). Concentrations of C1311 are greater in the cellular
      fraction of the blood than in the plasma, with disproportionately high
      concentrations occurring in the nucleated fraction.

PMID- 9771951
TI  - Drug resistance to 5-aza-2'-deoxycytidine, 2',2'-difluorodeoxycytidine, and
      cytosine arabinoside conferred by retroviral-mediated transfer of human cytidine
      deaminase cDNA into murine cells.
AB  - PURPOSE: The hematopoietic toxicity produced by the cytosine nucleoside analogs
      is a critical problem that limits their effectiveness in cancer therapy. One
      strategy to prevent this dose-limiting toxicity would be to insert a gene for
      drug resistance to these analogs into normal bone marrow cells. Cytidine (CR)
      deaminase can deaminate and thus inactivate 5-aza-2'-deoxycytidine (5-AZA-CdR),
      2',2'-difluorodeoxycytidine (dFdC) and cytosine arabinoside (ARA-C). The aim of
      this study was to determine if gene transfer of CR deaminase into murine
      fibroblast cells confers drug resistance to these cytosine nucleoside analogs and
      if this resistance can be prevented by the CR deaminase inhibitor, 3,4,5,6
      tetrahydrouridine (THU). METHODS: NIH 3T3 murine fibroblast cells were transduced
      with retroviral particles containing the human CR deaminase cDNA. Assays
      measuring CR deaminase activity as well as the inhibitory action of 5-AZA-CdR,
      dFdC and ARA-C on colony formation, were performed in the presence of different
      concentrations of THU. RESULTS: Retroviral-mediated transfer of the CR deaminase
      gene into 3T3 fibroblasts produced a considerable increase in CR deaminase
      activity. The transduced cells also showed significant drug resistance to 5-AZA
      CdR, dFdC and ARA-C, as demonstrated by a clonogenic assay. This drug resistance
      phenotype and elevated CR deaminase activity were reversed by THU. CONCLUSIONS:
      These findings indicate that the CR deaminase gene can potentially be used in
      cancer gene therapy for protecting normal cells against the cytotoxic actions of
      different cytosine nucleoside analogs. In addition, the CR deaminase-transduced
      cells can be used as a model for screening different CR deaminase inhibitors in
      an intact cellular system.

PMID- 9771953
TI  - The influence of relative body weight on toxicity of combination chemotherapy
      with cisplatin and etoposide.
AB  - PURPOSE: This study was conducted to determine whether there was any relationship
      between the adverse toxicity of combination chemotherapy and clinical values
      including age, sex, creatinine clearance (Ccr), body surface area and relative
      body weight. METHODS: Cisplatin at a dose of 80 mg/m2 on day 1 and etoposide at a
      dose of 100 mg/m2 on days 1, 2 and 3 were given to 42 consecutive patients with
      solid tumors. All patients had normal major organ function and received uniform
      hydration therapy. RESULTS: Body Mass Index as a measure of relative body weight
      was inversely correlated with the percentage decrease in white blood cells (P =
      0.0681) and platelet count (P = 0.0115). Body surface area was also inversely
      correlated with leukopenia (P = 0.0171) and thrombocytopenia (P = 0.0058). In
      contrast, age, sex and Ccr had no significant relationship with adverse toxicity.
      CONCLUSIONS: It is concluded that dose adjustment of combination chemotherapy
      with cisplatin and etoposide according to age or ideal body weight is not
      appropriate and that a conventional dose modification method based solely on body
      surface area is probably not sufficient to reduce interpatient variability of
      cancer chemotherapy. A pharmacokinetic and pharmacodynamic study of combination
      chemotherapy is warranted to establish the ideal dose modification method.

PMID- 9771954
TI  - Effect of adding the topoisomerase I poison 7-ethyl-10-hydroxycamptothecin (SN
      38) to 5-fluorouracil and folinic acid in HCT-8 cells: elevated dTTP pools and
      enhanced cytotoxicity.
AB  - PURPOSE: To determine the effect of combined treatment with 7-ethyl-10
      hydroxycamptothecin (SN-38, the active metabolite of irinotecan) and 5
      fluorouracil/ folinic acid (5FU/FA) in vitro using HCT-8 human intestinal
      adenocarcinoma cells. METHODS: Cell survival was examined using colony forming
      assays. Cell cycle distribution before and after treatment was assessed by flow
      microfluorimetry. Levels of thymidylate synthase (TS) and topoisomerase I (topo
      I) in untreated and treated cells were determined by immunoblotting. Changes in
      deoxynucleotide pools were examined by high-performance liquid chromatography.
      RESULTS: Clonogenic assays revealed that colony formation was decreased by 50%
      after a 24-h exposure to 8+/-2 nM SN-38 or 12+/-3 microM 5FU, the latter being
      assayed in the presence of 2 microM FA. When treatment with 5FU/FA was followed
      by SN-38, the cytotoxicity was similar to that observed with 5FU/FA alone. In
      contrast, when HCT-8 cells were exposed to both agents simultaneously or to SN-38
      followed by 5FU/FA, the cytotoxicity was greater than that of SN-38 or 5FU/FA
      treatment alone. Investigation of the mechanistic basis for this sequence
      dependence revealed that SN-38 treatment was associated with a dose- and time
      dependent decrease in conversion of [5-3H]-2'-deoxyuridine to [3H]-H2O and
      thymidylate in intact cells. Immunoblotting failed to reveal any decrease in TS
      protein that could account for the decreased activity. High-performance liquid
      chromatography revealed that SN-38 treatment was associated with increased levels
      of the deoxynucleotide dTTP and decreased levels of dUTP. Flow microfluorimetry
      revealed that a 24-h treatment wit 10 nM SN-38 resulted in accumulation of HCT-8
      cells in late S and G2 phases of the cell cycle, with a further increase in the
      G2 fraction during the 24 h after SN-38 removal. CONCLUSIONS: These observations
      are consistent with a model in which SN-38 sequentially induces diminished DNA
      synthesis, elevated dTTP pools, inhibition of dUMP synthesis and enhanced
      toxicity of 5FU/FA. Accordingly, sequencing of irinotecan and 5FU/FA might be
      important in combining these agents into an effective treatment for colorectal
      cancer.

PMID- 9771955
TI  - Determination of the cytoprotective agent WR-2721 (Amifostine, Ethyol) and its
      metabolites in human blood using monobromobimane fluorescent labeling and high
      performance liquid chromatography.
AB  - PURPOSE: WR-2721 [S-2-(3-aminopropylamino)ethylphosphorothioic acid] is a
      chemoprotective agent that is currently in pediatric clinical trials. It is a
      prodrug that is dephosphorylated by alkaline phosphatase to the active free thiol
      form, WR-1065 [S-2-(3-aminopropylamino)ethanethiol]. It is likely that adequate
      and sustained cellular levels of the drug are necessary for optimum
      cytoprotection. To date, a method to measure both plasma and cellular levels of
      WR-2721 and its metabolites in clinical samples has not been available. METHODS:
      In the study reported here the monobromobimane (mBBr) fluorescent labeling method
      was used to measure these levels when drug was added in vitro to blood samples
      from normal volunteers. In addition, we present pharmacokinetic data from a
      pediatric patient receiving WR-2721 (825 mg/m2 x 2). RESULTS: The results can be
      summarized as follows: (1) WR-2721 was detected in the patient's plasma with a
      half-life of about 10 min; (2) the WR-1065 concentration in the blood cellular
      fraction was similar to that of plasma; (3) both WR-1065 and WR-SS-low molecular
      weight (WR-SS-LMW) metabolites disappeared from plasma and the cellular fraction
      by 3.6 h after WR-2721 infusion; (4) a large proportion of WR-1065 was oxidized
      in plasma to WR-SS protein and WR-SS-LMW; (5) a large proportion of WR-1065 in
      the cellular fraction was oxidized to WR-SS-protein; (6) the WR-SS-LMW
      concentration in the cellular fraction was low; and (7) saturation of plasma and
      cellular protein binding sites was possible. CONCLUSIONS: The pharmacokinetic
      data that were generated with this technique could guide clinical trials using WR
      2721.

PMID- 9771956
TI  - Camptothecin delivery systems: enhanced efficacy and tumor accumulation of
      camptothecin following its conjugation to polyethylene glycol via a glycine
      linker.
AB  - PURPOSE: This study was designed to assess the circulatory retention, antitumor
      activity and tissue biodistribution of polyethylene glycol (PEG)-conjugated
      camptothecin-20-O-glycinate, PEG-beta-camptothecin (PEG-beta-CPT). PEG-beta-CPT
      is a novel water-soluble transport form (macromolecular prodrug) of the naturally
      derived antitumor drug, 20-(S)-camptothecin (CPT). METHODS: Circulatory retention
      studies were performed in nontumor-bearing mice injected intravenously (i.v.)
      with 875 mg/kg of PEG-beta-CPT. Antitumor activity was evaluated both
      intraperitoneally (i.p.) and i.v. in nude mouse xenograft models. Biodistribution
      studies were performed in nude mice bearing colorectal carcinoma xenografts with
      tritium-labelled PEG-beta-CPT and CPT injected i.v. RESULTS: PEG-beta-CPT had a
      blood t1/2alpha of approximately 6 min and a t1/2beta of 10.2 h. Significant
      antitumor activity was seen in all treated xenograft models. Biodistribution
      studies demonstrated that PEG-beta-CPT in saline provided more available labelled
      CPT in the circulation than unconjugated CPT dissolved in intralipid. In
      addition, it appeared that more labelled CPT accumulated in solid tumors when
      delivered in the PEG-beta-CPT form, with greater preference for tumor tissue than
      normal tissue. CONCLUSION: This soluble transport form of CPT and its underlying
      technology may have clinical application especially for the treatment of solid
      tumors.

PMID- 9771957
TI  - Phase II trial of titanocene dichloride in advanced renal-cell carcinoma.
AB  - Titanocene dichloride was capable of inhibiting the growth of different types of
      human tumors in vitro. A total of 14 patients with metastatic renal-cell
      carcinoma (RCC) received 270 mg/m2 titanocene dichloride every 3 weeks for 6
      weeks. Although the toxicities and side effects encountered were mild to
      moderate, no partial or complete response was detectable. In conclusion,
      titanocene dichloride has no advantage in the therapy of RCC.

PMID- 9771958
TI  - Serum protein binding of lerisetron, a novel specific 5HT3 antagonist, in
      patients with cancer.
AB  - The aim of this study was, (1) to characterize the serum protein binding of
      lerisetron, a new 5-hydroxytryptamine (5-HT3) receptor antagonist under
      investigation as an antiemetic agent, and (2) to measure the percentage of
      unbound lerisetron in cancer patients. The binding parameters were determined in
      human serum albumin (HSA), alpha1-acid glycoprotein (AAG) and in pooled serum
      from six healthy volunteers. Concentrations of lerisetron ranging from 50 ng/ml
      to 2 microg/ml were used. The serum protein binding of 14C-lerisetron (2
      microg/ml) was determined by ultrafiltration in three groups of individuals.
      Group I comprised healthy subjects (n = 11), group II comprised cancer patients
      undergoing radiotherapy (n = 9), and group III comprised cancer patients
      receiving chemotherapy (n = 18). The unbound concentration of lerisetron was
      measured in all samples by liquid scintillation counting. Concentrations of both
      AAG and HSA were also measured in all serum samples. The drug was extensively
      bound in pooled serum, involving a nonsaturated process. In HSA, lerisetron was
      also highly bound (4.04+/-0.8% unbound) and the protein binding was essentially
      unchanged within the studied concentration range of lerisetron. The extent of
      binding to AAG was high but significantly lower than in serum and in HSA and was
      also independent of lerisetron concentration. The unbound lerisetron was
      significantly decreased in group II cancer patients when compared with group I
      subjects (2.38+/-0.64% vs 3.70+/-0.70%; P < 0.001). No significant changes in
      lerisetron binding were observed in group III patients. HSA was diminished in
      both groups of patients and AAG was only significantly increased in group II.
      Unbound lerisetron was correlated with AAG in group II and with HSA in group III.

PMID- 9771959
TI  - Influence of piperacillin on the pharmacokinetics of methotrexate and 7
      hydroxymethotrexate.
AB  - The influence of concomitant administration of piperacillin (PIP) on the
      pharmacokinetic parameters of methotrexate (MTX) and 7-hydroxymethotrexate (7-OH
      MTX) was studied in rabbits. Six rabbits received an initial i.v. bolus (0.21 mg
      kg(-1)) followed by a constant-rate i.v. infusion of the drug (5 microg min(-1)
      kg(-1)) for 240 min. The PIP dose (30 mg kg(-1)) was repeated every 30 min until
      the end of the infusion period. The control group consisted of four rabbits
      treated the same way except for the addition of PIP. There were significant
      increases in the mean residence times found for MTX (MRTinf) and 7-OH-MTX
      (MRTm,inf) following PIP administration. Concomitant administration of PIP with
      MTX also produced significant 1.5- and 2.8-fold increases in the area under the
      curve of MTX and 7-OH-MTX, respectively. The total body clearance of MTX and the
      operative total body clearance of 7-OH-MTX significantly decreased, but in a less
      than proportional manner. The study demonstrates that the interaction between MTX
      and PIP is mainly due to the reduced clearance of both MTX and 7-OH-MTX combined
      with a slight increase in the formation clearance of the metabolite.

PMID- 9771960
TI  - Growth-inhibitory effects of the synthetic retinoid CD437 against ovarian
      carcinoma models in vitro and in vivo.
AB  - The activity of CD437?6-[3-(1-adamantyl)-4 hydroxyphenyl]-2-naphthalene
      carboxylic acid?, a relatively selective activator of RAR-gamma, was evaluated
      against four human ovarian-carcinoma cell lines : PE01, PE04 (a Pt-resistant in
      vivo-derived counterpart of PE01), PE01CDDP (a Pt-resistant in vitro-derived
      model of PE01) and PE014. Growth inhibition was observed after 3 and 6 days of
      exposure to sub-micromolar concentrations as assessed by a reduction in cell
      number. IC50 values against PE01, PE04, PE01CDDP and PE014 were 0.09, 0.21, 0.12
      and 0.28 microM (day 3) and 0.1, 0.14, 0.07 and 0.17 microM (day 6),
      respectively. Cisplatin-resistant cell lines were as responsive as cisplatin
      sensitive lines, indicating potential activity in resistant disease. CD437 was
      also evaluated against the PE04 xenograft grown in nude mice using daily doses of
      20 (days 0-4) and 10 mg/kg (days 0-4 and 7-11) given either by i.p. delivery or
      oral administration. Significant growth inhibition (P < 0.05) was obtained for
      both doses and by both routes. These data provide further support for the view
      that retinoids have value for the treatment of ovarian cancer.

PMID- 9771961
TI  - Normal development, oncogenesis and programmed cell death.
AB  - Meeting's Report -- June 2, 1998, Sugarload Estate Conference Center,
      Philadelphia, Pennsylvania, USA. A symposium on Normal Development, Oncogenesis
      and Programmed Cell Death, was held at the Sugarload Estate Conference Center,
      Philadelphia, Pennsylvania, USA sponsored by the Fels Cancer Institute, Temple
      University School of Medicine, with the support of the Alliance Pharmaceutical
      Corporation. The symposium was organized by Drs Dan A Liebermann and Barbara
      Hoffman at the Fels. Invited speakers included: Dr Andrei V Gudkov (University of
      Illinois) who started the symposium talking about 'New cellular factors
      modulating the tumor suppressor function of p53'; Dr Yuri Lazebnik (Cold Spring
      Harbor Laboratories) spoke about 'Caspases considered as enemies within'; Dr E
      Premkumar Reddy (Fels Institute, Temple University) talked about recent exciting
      findings in his laboratory regarding 'JAK-STATs dedicated signaling pathways'; Dr
      Michael Greenberg (Harvard University) spoke about 'Signal transduction pathways
      that regulate differentiation and survival in the developing nervous system'; Dr
      Richard Kolesnick's (Memorial Sloan-Kettering Cancer Center) talk has been
      focused at 'Stress signals for apoptosis, including Ceramide and c-Jun
      Kinase/Stress-activated Protein Kinase'; Dr Barbara Hoffman (Fels Institute,
      Temple University) described research, conducted in collaboration with Dr Dan A
      Liebermann, aimed at deciphering the roles of 'myc, myb, and E2F as negative
      regulators of terminal differentiation', using hematopoietic cells as model
      system. Dr Daniel G Tenen (Harvard Medical School), described studies aimed at
      understanding the 'Regulation of hematopoietic cell development by lineage
      specific transcription regulators'. Dr George C Prendergast (The Wistar
      Institute) talked about the 'Myc-Bin1 signaling pathway in cell death and
      differentiation. Dr Ruth J Muschel (University of Pennsylvania) spoke about work,
      conducted in collaboration with Dr WG McKenna, aimed at gaining a better
      understanding of 'Radioresistance and the cell cycle'. Finally Dr Donald Kufe
      concluded the symposium (Dana Farber Cancer Institute, Harvard Medical School)
      describing studies that were performed in his laboratory addressing the 'Role for
      the c-Abl tyrosine kinase in genetic recombination'.

PMID- 9771962
TI  - Human papillomavirus type 16 E7 protein sensitizes cervical keratinocytes to
      apoptosis and release of interleukin-1alpha.
AB  - Interleukin-1alpha (IL-1alpha) is a multifunctional cytokine that promotes
      inflammation, tissue remodeling and epithelial hyperplasia. Keratinocytes produce
      and sequester large amounts of biologically active IL-1alpha which can be
      released after injury or infection. We show that high level expression of human
      papillomavirus (HPV) type 16 E6 and E7 oncoproteins enhanced release of IL-1alpha
      from cultures of normal cervical keratinocytes (relative effectiveness E7 > E6/E7
      >> E6 > control). The amount of IL-1alpha released was directly related to the
      ability of E7 or E6/E7 to stimulate apoptosis. E7 proteins that bound the
      retinoblastoma protein (Rb) strongly (HPV-16 and -18) induced more IL-1alpha
      release than those that bound poorly (HPV-6 and an HPV-16 E7 24gly mutant).
      Furthermore, overexpression of the E2F-1 transcription factor, a downstream
      target of Rb, induced extensive apoptosis and IL-1alpha release. Apoptosis and IL
      1alpha release in response to growth factor removal occurred in part through a
      p53-independent pathway as coexpression of E6 and downregulation of p53 did not
      prevent either response. Immunohistochemical analyses showed that IL-1alpha was
      expressed by keratinocytes in normal cervical epithelia, low and high grade
      dysplasias, and cervical carcinomas. However, HPV-16 E6/E7 RNA expression and
      apoptosis increased in parallel in proliferating keratinocytes in severe
      dysplasias and carcinomas suggesting that IL-1alpha release is associated with
      progression to high grade disease. Thus, high level expression of the HPV-16 E7
      protein sensitizes keratinocytes to apoptosis which results in release of IL
      1alpha.

PMID- 9771963
TI  - The E7 protein of human papillomavirus type 16 sensitizes primary human
      keratinocytes to apoptosis.
AB  - The 'high risk' human papillomaviruses are associated with the development of
      anogenital carcinomas and their E6 and E7 genes possess immortalizing and
      transforming functions in several in vitro culture systems. Recently the E6 gene
      has also been shown to enhance the apoptosis of human mammary epithelial cells.
      To determine the apoptotic activity of these oncogenes in the natural host cell,
      we infected genital keratinocytes with retroviruses expressing either HPV-16 E6,
      E7, or both the E6 and E7 (E6/7) genes. Apoptosis was quantitated under normal
      growth conditions or when induced by tumor necrosis factor alpha/cycloheximide or
      sulfur mustard. In contrast to previous findings with mammary epithelial cells,
      the E6 gene did not significantly augment either spontaneous or induced
      apoptosis. E6 also did not suppress apoptosis in normal keratinocytes (despite
      dramatically reducing their p53 levels), suggesting that p53-independent events
      mediated this effect. In contrast, E7 increased both spontaneous and induced
      apoptosis as well as the cellular levels of p53 and p21 protein. Interestingly,
      co-expression of E6 abrogated E7-facilitated apoptosis by tumor necrosis factor
      alpha nearly completely, but had only a minor protective effect on sulfur mustard
      induced apoptosis in these cells, demonstrating at least in part the p53
      dependence and -independence of these two apoptotic pathways. Finally, our
      results indicate that the apoptosis of normal and E7-expressing keratinocytes is
      differentially affected by E6 expression and that E7, when unaccompanied by E6,
      sensitizes keratinocytes to apoptosis.

PMID- 9771964
TI  - Inactivation of protein kinase A is not required for c-mos translation during
      meiotic maturation of Xenopus oocytes.
AB  - It has been shown previously that protein kinase A (PKA) maintains Xenopus
      oocytes arrested at G2, at least in part by preventing c-mos translation, but how
      PKA controls c-mos translation is not known. Using microinjection of recombinant
      c-mos, which still activates MAP kinase in the presence of active PKA, we have
      found that PKA does not exert any effect on translation of endogenous c-mos if
      MAP kinase is first activated. Even though they accumulate c-mos and contain MAP
      kinase activity as high as control oocytes, oocytes do not exit G2 in the
      presence of active PKA. These results are discussed in connection with recent
      findings on regulation of c-raf activity.

PMID- 9771965
TI  - Expression of the antiapoptotic MCL1 gene product is regulated by a mitogen
      activated protein kinase-mediated pathway triggered through microtubule
      disruption and protein kinase C.
AB  - Members of both the mitogen activated protein (MAP) kinase and BCL2 gene
      families, acting in concert with other gene products, are involved in the
      regulation of cell viability. However, the relationship between these families,
      and the signal transduction networks that control viability-regulating genes, are
      only beginning to be elucidated. MCL1 is a viability-promoting member of the BCL2
      family that exhibits a rapid increase in expression in response to specific
      differentiation- and apoptosis-inducing stimuli. The signal transduction pathway
      involved in eliciting this increase has now been investigated. In the ML-1 human
      myeloblastic leukemia cell line, a rapid and sustained increase in
      phosphorylation of the extracellular signal-regulated kinase (ERK) members of the
      MAP kinase family was found to precede the increase in MCL1 expression produced
      by 12-O-tetradecanoylphorbol 13-acetate (TPA) or the microtubule-disrupting
      agents colchicine and vinblastine. ERK activation was necessary for the increase
      in MCL1, as inhibition of the increase in ERK phosphorylation (with the inhibitor
      PD 98059) prevented the increase in MCL1 expression and caused rapid cell death
      by apoptosis. In addition, other agents that markedly increased ERK
      phosphorylation (lipopolysaccharide, okadaic acid) also increased MCL1
      expression. In contrast, agents that did not have this marked effect did not
      increase MCL1. Upstream components in this ERK-mediated pathway were also
      identified, where the pathway was found to be stimulated by microtubule
      disruption acting through protein kinase C (PKC). These results indicate that
      expression of the MCL1 viability-enhancing gene is regulated through a
      cytoskeletal disruption-induced ERK-mediated signal transduction pathway. They
      therefore suggest a mechanism through which the cytoskeleton and MAP kinases can
      exert effects on cell viability.

PMID- 9771966
TI  - The Bcl-2 gene is differentially regulated by IL-2 and IL-4: role of the
      transcription factor NF-AT.
AB  - The murine TS1alphabeta T cell line expresses the anti-apoptotic protein Bcl-2
      upon IL-2 stimulation, whereas IL-4-mediated growth of this cell line proceeds in
      the absence of Bcl-2 expression. In addition, IL-4 stimulation inhibits Bcl-2
      expression and modulates its mRNA level. IL-2-induced DNA binding activity for
      these transcription factors is sensitive to phosphatidylinositol 3 kinase
      inhibitor wortmannin and to Rho inhibitor Clostridium difficile toxin B, which
      inhibit IL-2-induced Bcl-2 expression. NF-AT transcription factor appears to be
      the most important in the control Bcl-2 expression, since inhibition of the
      calcium-calmodulin-dependent phosphatase calcineurin, which regulates NF-AT
      activity, downregulates Bcl-2 expression in IL-2-stimulated cells. Constitutive
      expression of this phosphatase also upregulates Bcl-2 expression in IL-4
      stimulated cells. In addition, a dominant negative NF-AT expression vector
      downregulates Bcl-2 expression in IL-2-stimulated cells. These results suggest
      that IL-2 induction of Bcl-2 expression may be directly or indirectly mediated by
      NF-AT.

PMID- 9771968
TI  - The amino-terminal region of SV40 large T antigen is sufficient to induce hepatic
      tumours in mice.
AB  - The transforming activity of SV40 large T-antigen (Tag) depends on its binding to
      cellular proteins involved in the control of the cell cycle (p53, pRb, p300..)
      and on the J-domain region in the amino-terminus. We established transgenic lines
      expressing wild-type or Tag mutant proteins lacking one of the three transforming
      domains, to determine the respective contributions of these domains to hepatic
      tumour formation. Tag mutants with no pRb-binding domain or N-terminal fragment
      did not cause neoplastic liver abnormalities. The d11137 Tag mutant protein,
      which inhibits pRb function without affecting p53, induced hepatic tumours. These
      tumours grew significantly faster than those induced by wild-type Tag. Our
      results demonstrate different requirements for each of the inactivating functions
      of SV40 Tag in hepatocyte transformation and show that the loss of p53 function
      has only a moderate effect on hepatic tumour formation.

PMID- 9771967
TI  - Identification of a novel cDNA, encoding a cytoskeletal associated protein,
      differentially expressed in diffuse large B cell lymphomas.
AB  - Diffuse large B-cell lymphomas (DLBL) constitute an heterogeneous clinico
      pathological entity. To characterize molecular events related to histological
      subtypes, clinical presentation or outcome, we compared the mRNAs expressed in a
      limited series of DLBL by Differential display-reverse transcription (DDRT) and
      cloned a differential cDNA, that we called LB1. LB1 open reading frame encodes a
      683 amino-acid polypeptide that does not show significant homology upon
      comparison to protein databases, nor any structural domain relating LB1 to an
      already known protein family. Immunofluorescence analysis of transfected COS
      cells showed a cytoplasmic filamentous staining, indicating that LB1 protein is
      tightly associated with cytoskeletal fibers. Two LB1 transcripts, a major 3.6-3.9
      Kb and a minor 2.2 Kb transcripts, were detected among human haematopoietic and
      non-haematopoietic lines and tissues. LB1 transcripts were abundant in testis,
      thymus and in tumour derived cell lines, while barely detectable in liver,
      prostate and kidney. Concerning DLBL, LB1 expression was high in two cases of
      DLBL, and low or undetectable in four others, confirming the differential
      expression previously observed in the DDRT experiment. Furthermore, LB1 gene
      mapped to chromosome 13q14, a region that has been involved as a chromosomal
      breakpoint in DLBL. The cellular function of LB1 and its relationship with B cell
      maturation and/or oncogenesis remain to be established.

PMID- 9771970
TI  - An anchorage-dependent signal distinct from p42/44 MAP kinase activation is
      required for cell cycle progression.
AB  - Most normal cells require both mitogens and integrin-mediated attachment for
      growth. It is generally accepted that the p42/p44 MAP kinase module, which can be
      activated by both growth factors and adhesion, plays a critical role in G0 to S
      phase progression of quiescent cells. Studies on various cultured fibroblasts
      have shown that removal of anchorage leads to cell cycle arrest in G1 and it has
      been proposed that adhesion-dependent G1 progression requires the joint
      regulation of p42/p44 MAP kinase by integrins and growth factors. In quiescent
      CCL39 lung fibroblasts, MAP kinase activation in response to serum becomes
      compromised when cells are placed in suspension. Under these conditions, serum
      stimulated cells arrest their growth in mid-G1 with reduced cyclin D1 expression
      and increased p21Cip/Waf1 expression, as compared to their attached counterparts.
      To determine whether a casual link exists between suboptimal activation of MAP
      kinase in non-adherent cells and the observed G1 block, we used a variant of
      CCL39 stably expressing an estrogen-inducible activated-Raf-1 construct (deltaRaf
      1:ER). We found that even strong and sustained activation of MAP kinase with
      estradiol, in addition to serum, is not able to boost cyclin D1 expression levels
      or stimulate hyperphosphorylation of pRb in suspended CCL39-deltaRaf-1:ER cells.
      These results indicate that p42/p44 MAP kinase activation is not a limiting
      factor for G1 to S phase transit in absence of anchorage. Thus, at least one
      adhesion-mediated signalling event, distinct from MAP kinase activation is
      required for maximal cyclin D1 induction and hyperphosphorylation of pRb.

PMID- 9771969
TI  - AP-2 may contribute to IGF-II overexpression in rhabdomyosarcoma.
AB  - The human insulin-like growth factor II gene is regulated in a development
      dependent manner and is not expressed in most adult tissues. However, high levels
      of insulin-like growth factor II mRNA are detected in many human tumors including
      rhabdomyosarcoma, an embryonal tumor of skeletal muscle origin. In this study, we
      demonstrate that the developmentally regulated transcription factor AP-2 is
      expressed at higher levels in human fetal skeletal muscle and rhabdomyosarcoma
      cells compared to human adult skeletal muscle. Endogenous insulin-like growth
      factor II mRNA derived from the P3 as well as transfected P3 promoter activity
      were modestly and consistently increased to the same extent following treatment
      of the rhabdomyosarcoma cell line RD with forskolin, a compound implicated in AP
      2 transactivation. This effect of AP-2 on increased transcriptional activity was
      confirmed by nuclear run-on assays. Expression of AP-2B, a dominant-negative
      inhibitor of AP-2, suppressed the P3 promoter activity in AP-2 expressing RD
      cells. Furthermore, five AP-2 protected regions corresponding to six AP-2
      specific binding sites were detected in the insulin-like growth factor II P3
      promoter. These data together suggest that AP-2 may contribute to the high
      expression of IGF-II in rhabdomyosarcoma cells.

PMID- 9771971
TI  - The activation and composition of FiRE (an FGF-inducible response element) differ
      in a cell type- and growth factor-specific manner.
AB  - The expression of the heparan sulfate proteoglycan, syndecan-1, is induced both
      in keratinocytes and in fibroblasts during development and tissue regeneration.
      Here we report that in keratinocytes the syndecan-1 gene was stimulated by EGF
      but not by FGF-2. In fibroblasts it was stimulated by FGF-2 but not by EGF.
      Likewise, the recently discovered FGF-inducible response element (FiRE) on the
      gene of syndecan-1 was stimulated by FGF-2 in fibroblasts and by EGF in
      keratinocytes, but not vice versa. The FiRE has two binding sites for an
      activator protein-1 (AP-1), one for an FGF-inducible nuclear factor (FIN-1) and
      one for an upstream stimulatory factor-1 (USF-1). The growth factor-stimulated
      binding of these transcription factors, as well as their requirement for FiRE
      activation, varied between the two cell types. First, although AP-1s were
      required for activation of FiRE in both cell types, the binding of AP-1 to FiRE
      was increased by growth factor-stimulation only in fibroblasts and not in
      keratinocytes. Secondly, FiRE did not bind FIN-1 nor needed the FIN-1 binding
      site for EGF-stimulated activation in keratinocytes, in contrast to the FGF
      stimulated activation of FiRE in fibroblasts. Thirdly, EGF, which did not
      activate FiRE in fibroblasts, failed to activate FIN-1 in these cells. Finally,
      an USF-1 binding site that was necessary for activation of FiRE in keratinocytes
      was not needed in fibroblasts. These data suggest mechanisms by which members of
      the EGF- and FGF-families can differentially stimulate transcription through AP-1
      regulated elements in a cell type-specific manner.

PMID- 9771972
TI  - Analysis of WT1 target gene expression in stably transfected cell lines.
AB  - The Wilms' tumour suppressor gene WT1 encodes a zinc finger protein that is
      mutated in a subset of Wilms' tumours. Mutation screening and animal studies
      revealed essential roles during development and later function of the kidneys and
      the entire genitourinary system. Sequence similarity suggested a possible role
      for WT1 as a transcription factor. Indeed, sequence specific DNA binding and
      transcriptional activation or repression potential could be demonstrated in
      transient transfection assays with various reporter constructs. To identify
      endogenous WT1 target genes we established HEK293 cell lines expressing the
      different WT1 isoforms in a tetracycline dependent manner. Differential display
      PCR (ddPCR) was performed on RNA from stable WT1 transfected HEK293 cell lines
      and two other WT1 transfected lines (G401 and Saos-2). In an extended survey of
      several thousand ddPCR bands only few differences in intensity were seen and none
      of these could unambiguously be verified as being WT1 regulated by subsequent
      Northern blot analysis. In addition, almost none of the WT1 target genes
      identified to date in transient co-transfection assays could be confirmed by
      either ddPCR or Northern hybridization in the three stable transfected cell
      lines. Among the nine genes expressed, the only exceptions were CSF1 and to a
      lesser extent IGF1R being induced in Saos-2/G401 and HEK293 cells, respectively.
      At least two of the cell lines tested had previously shown clear biological
      effects though -- either WT1 dependent apoptosis (Saos-2) or greatly reduced
      tumorigenicity (G401). This suggests that WT1 may regulate only a very small set
      of genes that escape the detection methods used or it may not act as a
      transcription factor that influences steady state levels of mRNA.

PMID- 9771973
TI  - Acceleration of apoptotic cell death after the cleavage of Bcl-XL protein by
      caspase-3-like proteases.
AB  - Interleukin-2 (IL-2)-dependent T cell clone CTLL-2 underwent apoptosis by
      deprivation of IL-2 from culture medium. The decrease in the anti-apoptotic Bcl
      XL protein level was observed during apoptosis after IL-2 withdrawal. We found
      that Bcl-XL protein was cleaved to produce two 18 kDa fragments during CTLL-2
      cell apoptosis. When the activation of caspases was suppressed by overexpressing
      human Bcl-2 protein or by the addition of caspase inhibitors, cleavage of Bcl-XL
      protein was suppressed in vivo. Bcl-XL protein cleavage by incubation with
      apoptosed CTLL-2 cell lysate was suppressed by the caspase-3/CPP32-specific
      tetrapeptide inhibitor in vitro. Therefore, caspase-3/CPP32-like proteases were
      activated and involved in the cleavage of Bcl-XL protein during CTLL-2 cell
      apoptosis. We found that Bcl-XL protein was cleaved by caspase-3/CPP32 at two
      sites in the loop domain (i.e., HLAD61/S and SSLD76/A). The transfection of the
      carboxy-terminal 18 kDa Bcl-XL fragment increased the sensitivity to apoptosis.
      These results indicate that caspase-3/CPP32-like proteases cleaved anti-apoptotic
      Bcl-XL protein and resulted in accelerated apoptotic cell death.

PMID- 9771974
TI  - Transcriptional and translational downregulation of H-REV107, a class II tumour
      suppressor gene located on human chromosome 11q11-12.
AB  - The H-rev107 tumour suppressor was isolated as a gene specifically expressed in
      rat fibroblasts resistant toward malignant transformation by the activated HRAS
      gene (Sers et al., 1997; Hajnal et al., 1994). Here we describe the human
      homologue of the rat H-rev107 gene. The predicted rat and human proteins are
      highly conserved exhibiting an overall amino acid identity of 83%. The H-REV107-1
      gene is ubiquitously expressed with the exception of haematopoetic cells and
      tissues. In contrast, H-REV107-1 mRNA was found only in eight of 27 cell lines
      derived from mammary carcinoma, lung carcinoma, gastric carcinoma, kidney
      carcinoma, melanoma, neuroblastoma and other tumours. The H-REV107-1 protein was
      not detectable in any of these tumour cells. Loss of H-REV107-1 expression was
      not restricted to cultured human tumour cell lines, but also found in primary
      squamous cell carcinomas. Gross structural aberrations of the H-REV107-1 gene
      were absent in tumorigenic cell lines. Thus, the block to H-REV107-1 expression
      is achieved both at the level of transcription and translation. By fluorescence
      in situ hybridisation the human H-REV107-1 gene was localised to chromosome 11q11
      12.

PMID- 9771975
TI  - Transforming activity of the chimeric sequence formed by the fusion of collagen
      gene COL1A1 and the platelet derived growth factor b-chain gene in
      dermatofibrosarcoma protuberans.
AB  - As a consequence of a reciprocal translocation t(17;22)(q22;q13) and of
      supernumerary ring chromosomes derived from the t(17;22), a fusion between the
      platelet-derived growth factor b-chain (PDGF, c-sis proto-oncogene) and the
      collagen type 1A1 (COL1A1) genes has been recently described in
      dermatofibrosarcoma protuberans (DP), an infiltrating skin tumor (Simon et al.,
      1997). Although PDGFB has been implicated in transforming processes via autocrine
      and paracrine pathways, by the activation of the cognate receptor, no direct
      evidence of its involvement in neoplastic transformation of human tumours has
      been so far provided. In this report, we have tested the DNA from four DPs in the
      classical DNA transfection assay onto NIH3T3 fibroblast cell line. All the DNAs
      induced the formation of transformed foci in the transfected cultures whose
      derived cell lines were shown to contain a fused sequence comprising the human
      COL1A1 and PDGF genes. The relative breakpoint regions have been sequenced
      revealing that this gene fusion deleted exon 1 of PDGF and released the growth
      factor from its normal regulation. All the biochemical and biological assays were
      consistent with the model of an autocrine mechanism for NIH3T3 transformation by
      the human rearranged PDGFB gene involving the activation of the endogenous PDGF
      receptor.

PMID- 9771976
TI  - Up-regulation of CIR1/CROC1 expression upon cell immortalization and in tumor
      derived human cell lines.
AB  - Acquisition of the immortal phenotype by tumor cells represents an essential and
      potentially rate-limiting step in tumorigenesis. To identify changes in gene
      expression that are associated with the early stages of cell immortalization, we
      compared genetically matched pairs of pre-immortal and immortal human cell clones
      by mRNA differential display. Two transcripts, denoted CIR1 and CIR2, were
      identified which were up-regulated in immortal cells. Sequence analysis revealed
      CIR1 to be identical to the recently cloned CROC1/UEV-1 gene, whereas CIR2
      corresponds to an as yet uncharacterized 1.2 kb mRNA. A 5-6-fold elevation in
      CIR1/CROC1 expression and a 2-3-fold elevation in CIR2 expression were observed
      in SV40-transformed human embryonic kidney cells immediately following
      proliferative crisis, suggesting a potential role for these genes in
      immortalization. Expression of CIR1/CROC1 was found to be elevated also in a
      variety of immortal human tumor-derived cell lines, as compared to their normal
      tissue counterparts. These results are compatible with induction of CIR1/CROC1
      being an early event in the acquisition of immortality and with a role for this
      gene in the immortal phenotype of tumor cells.

PMID- 9771977
TI  - A monoclonal antibody-based characterization of autoantibodies against glutamic
      acid decarboxylase in adults with latent autoimmune diabetes.
AB  - Autoantibodies to glutamic acid decarboxylase (GAD) are an important marker of
      the autoimmune-mediated beta-cell destruction in insulin-dependent (Type I)
      diabetes. However, these autoantibodies are also found in patients with Stiff-man
      syndrome (SMS) without onset of diabetes and some diabetic patients who initially
      present as non-insulin dependent (Type II) diabetes later becoming insulin
      dependent, called as latent autoimmune diabetes in adults (LADA). To study the
      immune response to GAD in these LADA patients a competitive radiobinding assay
      based on murine monoclonal antibodies recognizing three different GAD regions was
      performed. The monoclonal antibodies against GAD recognize two different linear
      epitopes localized at the N- (amino acids 4-17) and C-terminus (amino acids 572
      585) and one conformation-dependent epitope region (amino acids 221-442 IDDM-E1)
      known to be immunodominant for diabetes-associated autoantibodies. All LADA sera
      (20/20) reduced substantially the 125I-GAD binding of the monoclonal antibodies
      reactive with the conformation-dependent epitope region IDDM-E1 and only 20% of
      these sera additionally diminished the 125I-GAD65 binding by those monoclonals
      reactive with the both linear epitopes. The SMS sera completely abolished the GAD
      binding of all three monoclonals, reflecting a broader repertoire including an
      immune response against the IDDM-E1, a conformation-dependent GAD65 epitope
      region, also revealed if the SMS sera are diluted to equivalent antibody
      concentrations. In summary, our results show that diabetes-associated GAD
      autoantibodies even in adult patients with a late autoimmune process
      preferentially recognize a conformation-dependent middle GAD65 region. An immune
      response to all three GAD epitope regions is seldom in these LADA patients and
      only detectable in association with high antibody titres.

PMID- 9771978
TI  - Cytokine mRNA profile of myelin basic protein reactive T-cell clones in patients
      with multiple sclerosis.
AB  - Autoimmune mechanisms involving T-cell responses to (a) myelin autoantigen(s),
      such as myelin basic protein (MBP), are thought to contribute to the pathogenesis
      of multiple sclerosis (MS). Cytokines may play a central role in the regulation
      of the pathogenic autoimmune responses in MS and the mediation of tissue damage
      in the disease. To study the cytokine expression of myelin reactive T-cells in
      MS, we determined the cytokine mRNA levels in a panel of blood derived MBP
      specific T-cell clones derived from MS patients (33 clones) and normal controls
      (21 clones), using a novel quantitative RT-PCR method. Our results demonstrate
      that MBP-specific T-cells, both from MS patients and control subjects,
      predominantly display a Th1- or Th0-like cytokine pattern. Although MS clones
      express higher levels of TNFalpha and IL-10 mRNA, these differences do not reach
      statistical significance. Interestingly, significantly increased TNFalpha and
      IFNgamma mRNA levels were observed among clones derived from HLA-DR2 positive
      versus HLA-DR2 negative MS patients. This HLA halpotype is known to be associated
      with MS. The high levels of TNFalpha and IFNgamma mRNA observed in MBP-reactive T
      cell clones from MS patients indicate an important role of these cytokines in the
      disease process. Our data lend further support to the pathogenic role of MBP
      reactive T-cells in MS.

PMID- 9771979
TI  - Syngeneic islet transplantation in prediabetic BB-DP rats--a synchronized model
      for studying beta-cell destruction during the development of IDDM.
AB  - During development of IDDM mononuclear cell infiltration is seen in the islets of
      Langerhans in both man and rodent models. This process is not synchronized in
      time and space. To create a synchronized model for investigation of the cellular
      and molecular events during IDDM development, we isolated and transplanted 200
      neonatal BB-DP rat islets under the kidney capsule of 30 day old BB-DP rats.
      Islet transplantations were also carried out from Wistar Furth (WF) to WF rats,
      from WF to Wistar Kyoto (WK) rats and from WK to BB-DP rats to compare disease
      occurrence in an islet syngraft with changes in islet syngrafts or allografts in
      non-diabetes prone recipients and with changes in islet allografts in diabetes
      prone recipients, respectively. Pancreata and grafts were harvested at pre
      scheduled time points before onset of diabetes and at onset of diabetes, and
      stained for insulin, MHC class I, MHC class II, alphabeta-TCR, CD4, CD8 or ED1.
      Diabetes incidence in the syngrafted BB-DP rats was 75% at 78 +/- 5 days of age.
      The incidence and time of onset of IDDM was unaffected by islet syngrafting.
      Positive correlations were found between the percentage of infiltrated islets in
      situ and the number of infiltrating cells in the islet syngraft from the same BB
      DP rats (p = 0.003-p < 0.0001, r = 0.5-0.7). The number of infiltrating cells
      regardless of cell type in the graft was inversely correlated to the graft
      insulin content (p = 0.0003-p < 0.0000, r = -0.6 to -0.8). The graft insulin
      content was 70% and 90% in BB-DP rats before onset of diabetes and BB-DP rats not
      developing diabetes respectively, and 30% in the diabetic rats (p < 0.01).
      Interestingly only 5% of the allografted BB-DP rats developed diabetes. No
      correlation was found between the number of infiltrating cells in the graft and
      islets in situ in the BB-DP rats not developing diabetes. Only baseline
      infiltration was seen in grafts from syngrafted WF rats. In allografted WF islet
      to WK rats graft rejection was seen 12 days after transplantation. No correlation
      was found between the number of infiltrating cells in the graft and islets in
      situ. In conclusion the cellular infiltration in syngeneic but not allogeneic
      islets grafted to 30 day old BB-rats mirrors that seen in islets in situ.
      Syngeneic islet grafting in BB-DP rats may be useful for studying the cellular
      and molecular events during the development of IDDM.

PMID- 9771981
TI  - The myth of lanolin allergy.
AB  - Lanolin has the reputation of being an important contact sensitizer. The market
      place abounds with products that are labeled "lanolin free". In fact, lanolin is
      at most a weak contact allergen. The supposed hazards of sensitization to lanolin
      products are a resultant of faulty science and failure to appreciate the
      limitations of patch testing. Lanolin allergy is a myth created mainly by
      overzealous professional patch testers. No one has succeeded in sensitizing
      animals or humans to lanolin or wool wax alcohols. Most of the case reports are
      false positives, in association with the angry back syndrome.

PMID- 9771980
TI  - Induction of a multiple sclerosis-like disease in mice with an immunodominant
      epitope of myelin oligodendrocyte glycoprotein.
AB  - Myelin oligodendrocyte glycoprotein (MOG) is postulated to be a target
      autoantigen in multiple sclerosis (MS). Here we investigated the
      encephalitogenicity of an immunodominant epitope of MOG, peptide 35-55, in
      various strains of mice. An MS-like disease was induced in NOD/Lt mice (H-2g7)
      and C57BL/6 mice (H-2b) by a single injection of MOG35-55 in CFA. The disease
      followed a relapsing-remitting course in NOD/Lt mice, whereas C57BL/6 mice
      developed a chronic paralytic disease. Histologically, the disease in both
      strains was characterized by cellular infiltration and multifocal demyelination
      in the CNS. Significant DTH type reactions to MOG35-55 were only seen in MOG
      susceptible animals, with the NOD/Lt mice showing the strongest responses.
      Susceptible mice also showed specific antibody responses to MOG35-55 but not to a
      panel of other MOG peptides. These results provide further evidence for the role
      of MOG as a highly autoantigenic molecule capable of inducing severe
      demyelinating disease.

PMID- 9771982
TI  - Contact sensitivities in palmar plantar pustulosis (acropustulosis).
AB  - Acropustulosis, or chronic palmar plantar pustulosis (PPP), is a phenomenon of
      recurrent sterile pustules, erythema, and scaling affecting the palms and soles.
      Its pathogenesis is unclear, and it is difficult to treat. The purpose of this
      study was to elucidate further the factors involved in causing PPP, thereby
      enhancing the ability to manage this disease. All cases of PPP seen at Mayo
      Clinic Scottsdale from 1987 to 1993 were reviewed. 21 patients with PPP were
      identified, 15 of whom had been patch tested. 9 of the 15 patients (60%) showed
      positive patch test results. Fragrance was the most common sensitivity, but
      nickel, formaldehyde, para-phenylenediamine, thiuram, neomycin, mercury, balsam
      of Peru, and cinnamic aldehyde sensitivities were demonstrated. Less important
      factors included atopy, fungal and bacterial infections, and irritation. Although
      the mechanism of this sterile pustulosis response does not depend solely on
      delayed hypersensitivity mechanisms, we believe that we have demonstrated such a
      large number of positive patch tests in this chronic pustular dermatosis that
      patch testing should be considered in the routine work-up of these patients.

PMID- 9771983
TI  - Objective assessment of nickel sulfate patch test reactions with laser Doppler
      perfusion imaging.
AB  - The laser Doppler perfusion scanning technique was used to assess the superficial
      blood flow of nickel sulfate hexahydrate patch test reactions. There was good
      agreement between laser Doppler and visual assessments when the highest
      assessment values of reactions were studied. Earlier detection of reactions was
      possible with the laser technique. There was great inter-individual variance in
      perfusion between identically tested patients. 4 patients were visually negative
      when a TRUE Test patch test dose of 0.20 mg/cm2 was applied for 48 h and the test
      area read 4x up to 168 h. These 4 showed a dose-related increase in perfusion and
      visually positive reactions using longer application times. The instrument
      allowed a dose reduction not possible for visual assessments. Reading transparent
      patches in contact with the skin through transparent semi-occlusive plastic foil
      or through windows in the tape strip over the patches, allowed us to detect
      perfusion at 48 h, where a longer application would have been needed using tape
      and visual assessments.

PMID- 9771984
TI  - Sesquiterpene lactone mix contact sensitivity and its relationship to chronic
      actinic dermatitis: a follow-up study.
AB  - In a retrospective case note analysis over a 4-year period, 0.9% of all patients
      tested with a standard patch test series (65 of 7600) were demonstrated to have
      clinically relevant responses to a sesquiterpene lactone (SQL) mix. Of these
      patients, 11 (17%) also had a diagnosis of chronic actinic dermatitis. This group
      made up 25% of all patients diagnosed as suffering from CAD in this 4-year
      period. These figures differ somewhat from those reported by our group in an
      initial 4-year period immediately following the introduction of the mix into our
      standard patch test series, when 1.5% of all patients tested had a clinically
      relevant response to the SQL mix, including 36% of all patients with a diagnosis
      of CAD. It is not uncommon for the prevalence of sensitivity to an allergen to be
      overestimated immediately following its introduction into routine testing.
      Possible reasons for our findings are discussed.

PMID- 9771986
TI  - Nickel release from tools on the Swedish market.
AB  - Nickel allergy in women has been thoroughly studied: its prevalence, the most
      important sources of sensitization, and risk factors for elicitation of
      dermatitis. Preventive measures have also been introduced. Nickel allergy in men
      has not, however, been equally focused on. Based on clinical experience, some
      publications indicating that tools may be a risk factor for nickel allergy and
      hand eczema in men, and the fact that large occupational groups regularly use
      tools, we decided to carry out a study, of the prevalence on the market of tools
      that release nickel. 27% of 565 hand-held tools with metal parts that come into
      contact with the skin were found to be dimethylglyoxime (DMG) test positive.
      Release of nickel and other metals into artificial sweat and composition of
      metals on the surface and in the base alloy were also studied. It is suggested
      that tool producers should consider nickel allergy and avoid nickel-releasing
      materials, and that analytical methods, relevant for nickel release from tools,
      should be further developed.

PMID- 9771985
TI  - Thimerosal positivities: the role of SH groups and divalent ions.
AB  - For a better understanding of the mechanistic details of the interactions of
      organomercury compounds inside the skin, 32 subjects who previously had given
      positive patch-test reactions to thimerosal (TH) and negative reactions to
      thiosalicylic acid, were divided into 2 groups. 16 subjects were repatch tested
      to ethylmercury chloride (EtHgCl) and to solutions containing EtHgCl mixed with L
      cysteine and glutathione, respectively. The remaining 16 were repatch tested to
      EtHgCl and to solutions containing EtHgCl mixed with chlorides of Zn, Mg, and Mn,
      respectively. The results showed that whilst L-cysteine, glutathione and ZnCl2
      were able to abolish or to reduce the positive reactions to EtHgCl, chlorides of
      Mg and Mn were unable to do so. Patch tests revealed that in causing positive
      reactions to TH, EtHg probably interacted with thiol groups and with Zn ions, as
      in biological systems when causing toxic effects. The limited number of TH
      reactions in the general population, the constant presence of concomitant
      positive reactions to EtHgCl and MeHgCl, and the lack of cross-reactivity with
      other organic or inorganic mercury compounds, lead us to speculate that reactions
      to TH are due to organomercury alkyl compounds, and that positive subjects have a
      constitutively reduced capability to metabolize organomercury compounds, rather
      than to reveal previous exposure.

PMID- 9771987
TI  - Allergic contact dermatitis due to Hygrophila salicifolia.

PMID- 9771988
TI  - Contact hypersensitivity to monobenzyl ether of hydroquinone used to treat
      vitiligo.

PMID- 9771989
TI  - Antimicrobials: preservatives, antiseptics and disinfectants.

PMID- 9771990
TI  - Persistent nodules at sites of hepatitis B vaccination due to aluminium
      sensitization.

PMID- 9771991
TI  - Allergy to 4-amino-3-nitrophenol in a hair dye.

PMID- 9771992
TI  - Allergic contact dermatitis from myrrh, a topical herbal medicine used to promote
      healing.

PMID- 9771993
TI  - The concordance of TRUE test applied in reverse directions on either side of the
      back.

PMID- 9771994
TI  - Human studies fail to detect the allergenic potential of cystamine bis-lactamide.

PMID- 9771995
TI  - Photocontact dermatitis from cinchocaine (dibucaine).

PMID- 9771996
TI  - Allergic contact dermatitis from parabens in a tar shampoo.

PMID- 9771997
TI  - Airborne contact dermatitis caused by microscopy immersion fluid containing epoxy
      resin.

PMID- 9771998
TI  - Comparison of the eliciting properties of 3 different propolis samples.

PMID- 9771999
TI  - Allergic contact blepharoconjunctivitis caused by phenylephrine, associated with
      persistent patch test reaction.

PMID- 9772001
TI  - Cutaneous drug reactions to piroxicam.

PMID- 9772000
TI  - Nickel contact dermatitis due to the needle of an infusion pump, confirmed by
      microanalysis.

PMID- 9772002
TI  - Patch test reactions and occupational dermatoses caused by hydrogen peroxide.

PMID- 9772003
TI  - Palmoplantar dermatitis may be due to phenol-formaldehyde resin contact
      dermatitis.

PMID- 9772004
TI  - Contact sensitivity induced by neomycin with cross-sensitivity to other
      aminoglycoside antibiotics.

PMID- 9772005
TI  - Propylene glycol in an isopropanol vehicle enhances immediate irritant reactions
      to benzoic acid.

PMID- 9772006
TI  - Carrier and inhibitory effects of surfactants on allergic contact reactions to 3
      dimethylaminopropylamine.

PMID- 9772007
TI  - Active sensitization to budesonide and para-phenylenediamine from patch testing.

PMID- 9772008
TI  - Identification of new allergens and non-irritant patch test preparations.

PMID- 9772009
TI  - Development and disease in proteinase-deficient mice: role of the plasminogen,
      matrix metalloproteinase and coagulation system.

PMID- 9772010
TI  - Impaired platelet binding of fibrinogen due to a lower number of GPIIB/IIIA
      receptors in polycythemia vera.
AB  - We have previously described a stimulus-specific defect in platelet aggregation
      in polycythaemia vera (PV) after stimulation with surface receptor dependent
      agonists such as platelet activating factor (PAF). In contrast, responses to
      phorbol myristate acetate (PMA) were normal. We now report that after PAF
      stimulation, using flow cytometry, the amount of fibrinogen bound to its receptor
      was significantly lower in PV platelets with a median MFI of 6.0 (range 4.1-17.3)
      compared to controls, 12.8 (range 8-21.3; n=11; p<0.01). We found no evidence of
      preactivation of PV platelets. Quantitative analysis of GPIIIa gave a
      significantly lower number of GPIIIa on resting PV platelets, 14300 subunits of
      GPIIIa (range 8500-15500) vs. 19800 for controls (range 13400-26800; n=12;
      p<0.01). Both patients and controls increased their number of receptors on the
      cell surface after stimulation with PAF and PMA, but the significant difference
      in the number of receptors per cell remained. Indirect evaluation of PAF receptor
      function showed that activation of CD 62 did not differ in PV and controls after
      PAF stimulation. Additionally, although the basal level of serotonin in platelet
      rich plasma was significantly lower in PV, there was a threefold increase of the
      basal level after stimulation with PAF for both PV and control platelets, also
      indicating a normal interaction of PAF with its receptor. Although our results
      indicate both an impaired PAF induced aggregation in PV and a lower number of
      GPIIb/IIIa complexes on single platelets, whether these phenomena are related
      remains uncertain.

PMID- 9772011
TI  - Expression of functional tissue factor on small vesicles of lipopolysaccharide
      stimulated human vascular endothelial cells.
AB  - We examined tissue factor expression on lipopolysaccharide-stimulated endothelial
      cells and their small vesicles by using specific antibodies and flow cytometry.
      Tissue factor functional activity was also assessed by activation of factor X.
      Endothelial cells were stimulated with 10 microg/ml of lipopolysaccharide in M
      199/bovine serum albumin. Flow cytometry showed that expression of tissue factor
      on endothelial cells reached a maximum at 6 hours after stimulation, whereas that
      on small vesicles reached a maximum after 12 hours. Factor X activation mediated
      by factor VIIa and tissue factor was observed over a similar time course and was
      inhibited by the addition of antitissue factor antibody. Immunoelectron
      microscopy suggested that small vesicles with expression of some tissue factor
      were produced from the surface of endothelial cells. Our findings thus showed
      that tissue factor on endothelial cells produced by lipopolysaccharide
      stimulation was partly released to small vesicles. This may cause disseminated
      intravascular coagulation and related coagulation disorders.

PMID- 9772012
TI  - Vitamin E and vitamin C supplement use and risk of incident Alzheimer disease.
AB  - Oxidative stress may play a role in neurologic disease. The present study
      examined the relation between use of vitamin E and vitamin C and incident
      Alzheimer disease in a prospective study of 633 persons 65 years and older. A
      stratified random sample was selected from a disease-free population. At
      baseline, all vitamin supplements taken in the previous 2 weeks were identified
      by direct inspection. After an average follow-up period of 4.3 years, 91 of the
      sample participants with vitamin information met accepted criteria for the
      clinical diagnosis of Alzheimer disease. None of the 27 vitamin E supplement
      users had Alzheimer disease compared with 3.9 predicted based on the crude
      observed incidence among nonusers (p = 0.04) and 2.5 predicted based on age, sex,
      years of education, and length of follow-up interval (p = 0.23). None of the 23
      vitamin C supplement users had Alzheimer disease compared with 3.3 predicted
      based on the crude observed incidence among nonusers (p = 0.10) and 3.2 predicted
      adjusted for age, sex, education, and follow-up interval (p = 0.04). There was no
      relation between Alzheimer disease and use of multivitamins. These data suggest
      that use of the higher-dose vitamin E and vitamin C supplements may lower the
      risk of Alzheimer disease.

PMID- 9772013
TI  - Prevalence and subtypes of dementia in a rural Chinese population.
AB  - We conducted a single-stage community-based study of dementia on all registered
      residents > or =65 years in age in a rural Chinese community. Neurologists
      conducted semistructured interviews and examined all participants; they also
      interviewed family members in cases where dementia was suspected. The diagnosis
      was made by consensus according to the criteria of the Diagnostic and Statistical
      Manual of Mental Disorders, 3rd ed, revised (DSM-III-R). Among the 2,055
      contacted individuals, 1,736 (84.5%) participated in the study and 44 ( 13 men
      and 31 women) were diagnosed as having dementia, including 35 (80%) with probable
      Alzheimer disease (AD) and 3 (7%) with vascular dementia (VsD). The rates of
      dementia were 0.5% for ages 65-74 years, 2.9% for ages 75-84 years, and 12.0% for
      ages 85-101 years. The overall rate was 2.5% for age > or =65 years. After
      controlling for age, neither a lack of formal education nor being a woman was a
      risk factor for dementia. At 2-year follow-up, 30 of the 44 demented participants
      had died, yielding a 2-year survival rate of 32%. The present results
      corroborated our previous findings of lower prevalence rates of dementia among
      the Chinese than among Western populations, and both genetic and sociocultural
      factors may have contributed to the low rates. The lack of neuroradiological
      imaging studies in the present study may have contributed to the finding of an
      unusually low rate of VsD.

PMID- 9772014
TI  - Factors associated with motor vehicle crashes in cognitively impaired older
      adults.
AB  - Because cognitive impairment might pose a safety risk for these drivers and the
      public, we examined what patient characteristics might be associated with motor
      vehicle crashes, in a retrospective study of all new referrals to a geriatric
      clinic specializing in memory and behavior problems between July 1, 1990 and June
      30, 1995. During this time, 989 new patients were evaluated by the clinic staff.
      Driving data were available from 634 patients. The only factor significantly
      associated with crashes was driving alone (odds ratio = 2.23, 95% confidence
      interval = 1.20-4.15). Twenty-five percent of patients who drove alone had
      caregiver-reported crashes in the previous 5 years, compared with 13% of those
      who drove only with a passenger. Patients who drove alone were more likely to
      have spousal caregivers than patients who drove only with a passenger (72% vs.
      58%, p = 0.028). Thus, cognitively impaired patients allowed to drive alone were
      more likely to have been involved in crashes than patients not driving alone.
      However, the causal nature of this association cannot be established with the
      present design. Prospective studies are required to determine if the presence of
      a co-pilot represents a safe strategy to extend driving privileges in cognitively
      impaired older drivers.

PMID- 9772015
TI  - Mortality associated with an influenza outbreak on a dementia care unit.
AB  - The purpose of this study was to describe an episode of increased mortality,
      whose cause was initially unknown. This retrospective cohort investigation was
      conducted on a dementia special care unit of a Department of Veterans Affairs
      facility, with more than 75% of residents clinically diagnosed with dementia of
      the Alzheimer type. One hundred five residents residing in the facility during
      February 1995 were included as subjects. A cluster of deaths occurred, triggering
      the investigation. Ultimately, 21 deaths (three times greater than any previous
      month in the past 5 years) occurred during the 1-month period. Measures included
      the presence of clinical influenza-like illness based on signs, serology, and
      autopsy results. Of the 105 residents, 45 (42.8%) met the clinical definition for
      influenza-like illness. Eight autopsies were performed, and the causes of death
      consisting of bronchopneumonia in seven and aspiration pneumonia in one were
      compatible with influenza. There were no differences among those who died from
      those who lived with regards to age, race, gender, clinical influenza-like
      illness, vaccination status, diagnosis of Alzheimer disease, or duration of
      dementia (all p > or = 0.2). However, those who died were at a higher risk of
      dying due to a greater number of coexisting conditions (p < 0.01). Also, overall
      the groups differed in Mini-Mental State Examination and Bedford Alzheimer
      Nursing Scale scores with those who died being more impaired (p < 0.01). Thus,
      the presentation of influenza-like illness can be subtle in onset,
      underappreciated in this population, and not recognized until excess mortality,
      which affects the most frail, is noted. Care providers need to be vigilant during
      the winter months for the presence of influenza.

PMID- 9772016
TI  - Relationship of disease severity to decline on specific cognitive and functional
      measures in Alzheimer disease.
AB  - Previous studies have shown that the sensitivity of global cognitive and
      functional measures to change in Alzheimer disease is related to overall disease
      severity. The present study assessed the sensitivity to decline, over a 12-month
      interval, for individual items of the cognitive portion of the Alzheimer Disease
      Assessment Scale (ADAS-Cog), the Instrumental Activities of Daily Living Scale
      (IADLS), and the Physical Self-Maintenance Scale (PSMS). This study was conducted
      in an effort to identify individual items likely to be sensitive at different
      stages of the disease. A total of 151 patients with Alzheimer disease were
      classified into four dementia categories by baseline scores on the Blessed Test
      of Information, Memory, and Concentration. The patients were retested after 12
      months. For the individual items and for total scores on both the ADAS-Cog and
      the IADLS, rate of change was greater for patients in the moderate and severe
      categories than for mild or very severe patients. For individual items and for
      the total score on the PSMS, rate of change was greater for severe and very
      severe patients than for patients with mild or moderate disease.

PMID- 9772017
TI  - Sensitivity and specificity of some neuropsychological markers of Alzheimer
      dementia.
AB  - A standardized neuropsychological test battery was administered to 167 patients
      with different forms of mild-to-moderate dementia: probable Alzheimer dementia
      (AD: n = 49), multi-infarct dementia (n = 43), idiopathic Parkinson disease with
      dementia (n = 35), depressive pseudodementia (n = 26), and progressive
      supranuclear palsy (n = 14). Results obtained were used (a) to analyze the
      profiles of cognitive impairment shown by the different dementia groups; (b) to
      assess the incidence of some neuropsychological patterns that we hypothesized to
      be more characteristic of AD, in the various groups; and hence (c) to evaluate
      the reliability of these patterns as diagnostic markers of AD. Four of the
      patterns investigated were derived from a verbal learning task (Rey's Auditory
      Verbal Learning test): (1) absence of the primacy effect; (2) tendency to produce
      intrusion errors during free recall of a word list; (3) absolute decay of memory
      trace; and (4) tendency to produce false alarms during delayed recognition of the
      same word list. Two additional patterns were derived from visual-spatial tasks
      (copying drawings and Raven's Coloured Progressive Matrices): (5) occurrence of
      the closing-in phenomenon in copying drawings; and (6) tendency to choose
      globalistic or odd responses in Raven's matrices. Though all the six patterns
      were somewhat useful for identifying AD patients, no pattern met the criteria of
      being both highly sensitive and highly specific, which should characterize an
      ideal marker. In fact, intrusions and false alarms were observed in many AD
      patients, but also in patients affected by other forms of dementia. The absence
      of the primacy effect, the closing-in phenomenon, and the absolute decay of
      memory trace were more specific, but could be observed in only one-third of AD
      patients. We also computed the number of positive patterns shown by each patient
      and assumed the presence of two or more patterns as a global index suggestive of
      a dementia of the Alzheimer type. With this cumulative method, a higher level of
      sensitivity and specificity was achieved in the identification of AD patients.

PMID- 9772018
TI  - Age at onset and visuocognitive disturbances in Alzheimer disease.
AB  - We examined the relation of age at onset and visuocognitive disturbances in
      Alzheimer disease (AD) using a large sample of patients, quantitative
      neuropsychological measures, and multivariate statistics controlling for gender,
      education, stage of dementia, and disease duration. Significant positive
      coefficients were obtained with forward and backward digit and visual spans,
      visual counting, copying Rey complex figure, and block design task. The results
      indicated that patients with early-onset AD performed worse than late-onset AD
      patients on these tasks. There was no significant effect of age at onset on
      identification of overlapping figures, visual form discrimination, or Raven's
      colored progressive matrices. These findings confirm the greater attentional and
      visuospatial impairments in early onset patients when these confounding factors
      were controlled for, although no significant effect of age at onset in
      visuoperceptual function was observed.

PMID- 9772019
TI  - Slowing on quantitative spectral EEG is a marker for rate of subsequent cognitive
      and functional decline in early Alzheimer disease.
AB  - The relation between quantitative spectral electroencephalogram (qEEG) parameters
      and subsequent rate of cognitive, functional, and behavioral decline in 82
      consecutive patients with early probable Alzheimer disease (NINCDS-ADRDA
      criteria) was examined in a prospective study. The qEEG was performed at initial
      examination and global cognitive function, activities of daily living, and
      behavior were assessed at initial evaluation and after a period of 6 months.
      Using multiple linear regression analysis, higher frontocentral and parieto
      occipital theta values, lower parieto-occipital beta values, and lower peak
      frequency were significantly associated with more decline in global cognitive
      function over the follow-up period. In addition, lower parieto-occipital beta
      values were significantly related to more decline in activities of daily living.
      These associations were independent of demographic (age, sex, and education) and
      disease characteristics [initial Cambridge Examination for Mental Disorders of
      the Elderly Cognitive test (CAMCOG) or Mini-Mental State Examination scores,
      estimated duration of symptoms, estimated prior rate of decline, and dementia
      severity]. In a separate multiple logistic regression analysis, prediction of
      rapidly progressive decline, defined as 8 or more points decline in CAMCOG scores
      (n = 21), could be made with parieto-occipital and frontocentral beta values. The
      results suggest that slowing on qEEG is a marker for subsequent rate of cognitive
      and functional decline in mildly demented AD patients, independent of demographic
      or disease characteristics.

PMID- 9772020
TI  - Reduced interhemispheric EEG coherence in Alzheimer disease: analysis during rest
      and photic stimulation.
AB  - The present study was conducted to examine interhemispheric electroencephalogram
      (EEG) coherence at rest and during photic stimulation (5, 10, and 15 Hz) in 10
      patients with presenile dementia of the Alzheimer type (AD; mean age at onset, 56
      years) and 10 sex- and age-matched control subjects. Compared with the control
      subjects, the AD patients had significantly lower interhemispheric coherence in
      the resting EEG for the delta, theta-2, alpha, and beta-1 frequency bands. EEG
      analysis during photic stimulation also showed that the patients had
      significantly lower coherence, irrespective of the stimulus frequency. In
      addition, when we examined the changes in coherence from the resting state to the
      stimulus condition (i.e., coherence reactivity), significant group differences
      were found at the brain region primarily involved in visual functioning; the
      patients had significantly smaller coherence reactivity to photic stimulation at
      5 and 15 Hz over the posterior regions. These findings suggest that AD patients
      have an impairment of interhemispheric functional connectivity in both
      nonstimulus and stimulus conditions. The findings also suggest a failure of
      normal stimulation-related brain activation in AD.

PMID- 9772021
TI  - Comparison of pathological diagnostic criteria for Alzheimer disease.
AB  - Because the clinical picture of Alzheimer disease (AD) is often difficult to
      discriminate from other dementing illnesses, the diagnosis of AD requires
      neuropathological confirmation. However, for the pathological diagnosis of AD,
      there are no unanimously accepted criteria. The three currently used sets of
      pathological criteria (Khachaturian: Khachaturian, Arch Neurol 1985;42:1097-105;
      Tiemy: Tierney et al., Can J Neurol Sci 1986; 13:424-6; CERAD: Mirra et al.,
      Neurology 1991;41:479-86) for the disease differ from each other considerably. We
      applied these criteria to the first 43 consecutive subjects (37 demented) with no
      neuropathology other than AD-type pathology from autopsies after longitudinal
      prospective clinical study in the Oxford Project to Investigate Memory and Ageing
      (OPTIMA). The results show that the CERAD category of definite AD corresponds
      closely with the cases that fulfill Tierney A3 inclusion criteria for AD. The
      combined CERAD categories of possible, probable, and definite AD correspond
      closely to cases fulfilling Khachaturian criteria forAD. The influence of a
      clinical diagnosis of dementia when Khachaturian and CERAD criteria were applied
      was considerable because between 9.3% and 90.7% of patients would have been
      categorized differently depending on whether clinical dementia was present or
      absent.

PMID- 9772022
TI  - Role of familial factors in late-onset Alzheimer disease as a function of age.
AB  - Whereas early-onset Alzheimer disease (AD; usually onset at age < 50 years) has
      been defined with genetic mutation on chromosomes 1, 14, and 21, the degree of
      familial contribution to late-onset AD is unclear. Further, it is uncertain if
      subgroups of late-onset AD exist. To examine the influence of familial factors as
      a function of age in late-onset AD we investigated lifetime risks and age
      specific hazard rates of AD-like illness among late-onset AD probands' and
      controls' first-degree relatives, using questionnaires and medical records. As
      part of a longitudinal study on aging and AD, we studied 78 AD probands with age
      of onset > or =50 years (28 "definite" and 50 "probable" AD according to
      NINCDS/ADRDA criteria) and 101 healthy old controls seen since 1981. Both
      probands and controls were screened rigorously with medical tests and brain
      imaging and seen regularly until autopsy. Multiple informants and medical records
      were used for first-degree relatives. Among first-degree relatives, 49 secondary
      cases of AD-like illness were found for the AD probands' relatives (391 relatives
      40 years old or older) compared with 20 cases among controls' relatives (456
      relatives 40 years old or older). Relatives of AD probands had a significantly
      increased lifetime risk of AD-like illness of 52.8+/-11.4% by age 94 years
      compared with a lifetime risk in relatives of controls of 22.1+/-5.8% by age 90
      years. Age-specific hazard rates in relatives of AD probands increased until the
      75-79-year age interval and then decreased; in contrast the age-specific hazard
      rates increased in relatives of controls after the 80-84-year age interval. To
      determine if a dividing line exist among late-onset AD, several cutoff ages were
      used in our study to compare cumulative risk curves of AD-like illness between
      relatives of late-onset probands and relatives of late-late-onset probands.
      Differences in the pattern of cumulative incidence of AD in relatives showed that
      67-71 years is the range for a dividing line between late- and late-late-onset
      AD. Age-specific hazard rates of AD in relatives supported a difference between
      late- and late-late-onset. Whereas these rates increased until the 75-79-year age
      interval and then decreased in late-onset AD, the rates began increasing after
      the 65-69-year age interval and through the oldest age interval in both late-late
      onset AD and control groups. Our results support the concept that familial
      factors exist in late-onset AD and that different familial factors may exist in
      late-onset AD subgroups.

PMID- 9772023
TI  - Reduced levels of cholesterol, phospholipids, and fatty acids in cerebrospinal
      fluid of Alzheimer disease patients are not related to apolipoprotein E4.
AB  - Apolipoprotein E4 (apoE4) has been identified as a major risk factor for
      Alzheimer disease (AD). Previously it has been reported that levels of apoE are
      reduced in cerebrospinal fluid (CSF) of AD patients. Because it is known that
      apoE4 affects plasma lipid metabolism, we examined whether the presence of apoE4
      might correlate with an altered lipid metabolism in the CSF of control subjects
      and AD patients. ApoE and lipid concentrations were determined in postmortem
      ventricular CSF of 30 neuropathologically confirmed AD cases and 31 age-matched
      control patients. ApoE genotyping was performed on frozen brain tissue of the
      same patients. In line with other reports, we found an increased APOE*4 allele
      frequency in the AD group (0.461) when compared with the control group (0.225).
      ApoE levels in CSF of AD patients were not significantly reduced when compared
      with the controls (mean +/-SD: 63+/-55 and 82+/-62 microg/dL for AD and controls,
      respectively). However, in the CSF of AD patients levels of free and esterified
      cholesterol (0.13+/-0.09 and 0.25+/-0.19 mg/dL, and 0.25+/-0.19 and 0.42+/-0.34,
      respectively), phospholipids (0.2+/-0.1 and 3.5+/-5.0 mg/dL) and, suprisingly,
      also fatty acids (4.5+/-3.2 and 28.0+/-18.5 micromol/L) were found to be
      significantly reduced. After correction for age, sex, postmortem delay, and pH
      the levels of phospholipids, fatty acids, and free cholesterol were still
      significantly reduced (p = 0.021, p = 0.026, andp = 0.012, respectively). The
      apoE and lipid levels in CSF of AD-and control patients appeared not to be
      affected by the number of APOE*4 alleles. In conclusion, our results suggest an
      altered lipid homeostasis in the brain of AD patients that is not related to the
      presence of apoE4. It is, therefore, unlikely that an effect of apoE4 on brain
      lipid metabolism is the underlying mechanism behind the role of apoE4 in the
      development of AD.

PMID- 9772024
TI  - No association between familial Alzheimer disease and cytochrome P450
      polymorphisms.
AB  - Four different loci have been found to be involved in the development of familial
      Alzheimer disease (AD). The epsilon4 allele of the apolipoprotein E gene on
      chromosome 19 is a susceptibility factor for AD, and in a small number of AD
      families, dominant mutations with high penetrance are operating in genes on
      chromosomes 1, 14 and 21. However, the disease in many familial AD cases cannot
      be explained by these genes; thus, other genetic factors involved in the etiology
      of AD should exist. Recently, an association between the cytochrome P450 2D6B
      (CYP2D6B) allele and the Lewy body variant of AD was reported. In the present
      study, 54 unrelated Swedish familial AD patients and 56 age- and sex-matched
      healthy controls were studied with respect to the two genetic polymorphisms of
      oxidative drug metabolism, CYP2D6 and CYP2C19. No significant association was
      found between the defect CYP2D6A and -B or CYP2C19ml and -m2 alleles and familial
      AD patients, with the exception of a lower frequency of CYP2D6B in the male AD
      cases.

PMID- 9772025
TI  - Scintigraphy with 123I-serum amyloid P component in Alzheimer disease.
AB  - The neuropathology of Alzheimer disease (AD) includes cerebral and
      cerebrovascular amyloid deposits composed of A(beta) protein. Extracerebral
      deposits of A(beta), identified immunohistochemically, have also been reported
      but without evidence for the presence of amyloid fibrils. Serum amyloid P
      component (SAP) is a normal plasma glycoprotein that binds to the fibrils in all
      types of amyloid deposit, and radiolabeled SAP is a specific, sensitive,
      quantitative diagnostic tracer for systemic amyloid deposits in vivo. However, we
      report that in 11 patients with probable or definite AD, conventional whole body
      planar scintigraphy after injection of 123-SAP revealed no detectable
      localization of tracer within the brain or elsewhere. Significant amounts of
      systemic extracerebral A(beta) amyloid are thus probably not a feature of AD.
      Also, although plasma-derived SAP is always present in the cerebral and
      cerebrovascular amyloid lesions of AD, there was insufficient accumulation of
      injected labeled SAP to be detected by the present routine methodology.

PMID- 9772026
TI  - Tau protein in cerebrospinal fluid: a new diagnostic and prognostic marker in
      Alzheimer disease?
AB  - Tau is the main protein of paired helical filaments. It can be detected and
      measured in cerebrospinal fluid (CSF) and for this reason it has been proposed as
      a possible in vivo marker of Alzheimer disease (AD). To evaluate the usefulness
      of CSF tau in the diagnosis of AD we measured it in patients with AD, frontal
      lobe dementia (FLD), vascular dementia (VD), and in healthy controls by means of
      a specific enzyme-linked immunosorbent assay test. Individuals with AD had
      significantly higher tau levels than FLD, VD, and controls. Individuals with late
      onset AD had significantly higher levels than those with early onset disease. In
      AD, CSF tau level did not correlate with age, duration, or severity of the
      disease, whereas a correlation with age was found in FLD and controls. In the
      nine AD patients in whom CSF tau measurement was repeated after 2 years, mean
      levels did not differ from baseline, although a worsening of cognitive
      performances occurred. The overlap among the different groups and the absence of
      any modification over time suggest that CSF tau measurement, more than in
      confirming or staging overt AD, might be useful in revealing the disease at its
      preclinical phase.

PMID- 9772027
TI  - Longitudinal study of inflammatory factors in serum, cerebrospinal fluid, and
      brain tissue in Alzheimer disease: interleukin-1beta, interleukin-6, interleukin
      1 receptor antagonist, tumor necrosis factor-alpha, the soluble tumor necrosis
      factor receptors I and II, and alpha1-antichymotrypsin.
AB  - There is evidence consistent with the hypothesis that inflammatory and immune
      mechanisms are involved in the pathogenesis of Alzheimer disease (AD). We have
      investigated whether the levels of inflammatory associated proteins in serum or
      lumbar cerebrospinal fluid (CSF) reflect the progressive cognitive decline and
      brain atrophy of AD-patients. Levels of interleukin-1beta(IL-1beta), IL-1
      receptor antagonist (IL-1ra), interleukin-6 (IL-6), tumor necrosis factor-alpha
      (TNF-alpha), the soluble TNF receptors type I and II (sTNFR I and II), and the
      acute phase protein alpha1-antichymotrypsin (x1-ACT) were determined in paired
      serum and CSF samples taken yearly over a period of 2-5 years from pathologically
      confirmed AD patients (n = 8) and normal controls or non-AD subjects with other
      CNS pathology (n = 9). No significant differences were found between AD subjects
      and controls in the mean levels of the above mediators. There was also no
      correlation in either subject group between the levels of these inflammatory
      mediators in serum or CSF, and the change in cognitive status or the progression
      of the atrophy of the medial temporal lobe measured by X-ray computed tomography
      (CT). The concentrations of IL-1beta, IL-6, and TNF-alpha were determined in
      brain tissue specimens of five to nine different brain regions in six of the AD
      patients and four of the non-AD subjects. The levels of IL-1beta and IL-6 in the
      various brain regions were not significantly different in the AD and the non-AD
      group. However, in AD patients the level of TNF-alpha was significantly lower in
      the frontal cortex (32%, p = 0.024), the superior temporal gyrus (57%, p =
      0.021), and the entorhinal cortex (49%, p = 0.009) compared with non-AD subjects.
      Low levels of TNF-alpha in the brain areas that showed neuropathology in AD may
      indicate a dysregulation of the inflammatory process in AD. Despite this finding,
      this study does not support the use of measurements of any of the inflammatory
      mediators investigated here as a diagnostic parameter for AD, due the large
      overlap in the levels of these factors between AD patients and other subjects,
      and the poor relation to clinical signs of AD.

PMID- 9772028
TI  - Long-term tacrine treatment in three mild Alzheimer patients: effects on
      nicotinic receptors, cerebral blood flow, glucose metabolism, EEG, and cognitive
      abilities.
AB  - The effect of long-term treatment with tacrine (tetrahydroaminoacridine) was
      studied in three Alzheimer patients (aged 57, 64, and 68 years) with mild
      dementia. All three patients had a Mini-Mental State Examination score of 24/30
      and carried at least one apolipoprotein E (ApoE) epsilon4 allele. Tacrine was
      given in doses between 80 and to 160 mg daily for 13-31 months. A lower tacrine
      concentration was observed generally in cerebrospinal fluid (CSF) compared with
      plasma. The acetylcholinesterase activity in CSF tended to be increased following
      longer periods of tacrine treatment, whereas the butyrylcholinesterase activity
      was decreased. The three patients repeatedly underwent positron emission
      tomography investigation of cerebral blood flow, nicotinic receptors, cerebral
      glucose metabolism, and electroencephalogram (EEG) and cognitive tests. Positive
      influences on these parameters were observed following both short-term and long
      term treatment with tacrine. Improvement of nicotinic receptors (measured as 11C
      nicotine binding), cerebral blood flow, EEG, and some cognitive tests (trail
      making test, block design test) occurred earlier after initiation of tacrine
      treatment compared with the glucose metabolism, which was increased after several
      months of tacrine treatment. An improvement in attention (trail making test) was
      observed following tacrine as sign for frontal lobe activation (EEG). The
      functional effects of tacrine in Alzheimer patients appeared to be related to
      both dose and length of cholinesterase inhibitor treatment.

PMID- 9772029
TI  - (S)-(-)-[11C]nicotine binding assessed by PET: a dual tracer model evaluated in
      the rhesus monkey brain.
AB  - A dual tracer model, consisting of the administration of 15O-water and (S)-(-)
      [11C]nicotine in close succession, is suggested to assess nicotine binding in the
      brain. Regional cerebral blood flow (rCBF) determined by 15O-water was used to
      flow compensate two nicotine model parameters, k1 and k2, obtained in a two
      compartment kinetic model. In the present study, this dual tracer approach was
      evaluated in the rhesus monkey by altering the rCBF or by administering (S)-(-)
      [11C]nicotine at either high or low specific radioactivity. The model parameter,
      k2' = k2/rCBF, was found to be independent of rCBF in different regions of
      interest in the monkey brain. The parameter, k2', increased significantly when
      (S)-(-)-[11C]nicotine was given at low specific radioactivity, indicating lower
      nicotine binding in the brain. Thus, this observation implies an influence on
      specific receptor binding on the corrected efflux rate constant. This dual tracer
      model may be useful in evaluating nicotine binding changes in the human brain and
      the effect of drug treatment in neurodegenerative disorders such as Alzheimer
      disease.

PMID- 9772030
TI  - Effectiveness of traditional Chinese medicine in Alzheimer disease.
AB  - Effects of traditional Chinese medicine on dementia, P300, cerebral blood flow,
      and cerebrospinal fluid (CSF) examination were investigated. Ten patients with
      Alzheimer disease (AD) who agreed to take traditional Chinese medicine were
      studied. The traditional Chinese medicine was given for 3 months and the Mini
      Mental State Examination (MMSE), P300 examination, cerebral blood flow
      examination, and CSF examination were performed before and after taking the
      traditional Chinese medicine. The scores of the MMSE, the P300 latency, and blood
      flow in the cerebral cortex in AD improved with treatment with the traditional
      Chinese medicine. The concentration of alpha-aminobutyric acid in the CSF
      decreased with treatment with the traditional Chinese medicine. The improvement
      is considered to be not a placebo effect. Key Words: T

PMID- 9772031
TI  - From slowly progressive amnesic syndrome to rapidly progressive Alzheimer
      disease.
AB  - A 57-year-old woman had a neuropsychologically documented 5-year history of a
      slowly progressive amnesic syndrome followed by a 1-year history of rapidly
      progressive dementia. There was no family history of dementia. Magnetic resonance
      imaging failed to show a structural basis, electroencephalography failed to show
      changes of Creutzfeldt-Jakob disease, and cerebrospinal fluid examination was
      normal. A diagnosis of Alzheimer disease was confirmed by brain biopsy. The
      abrupt change in disease course was unique but suggested probable overlap between
      posited subtypes of Alzheimer disease.

PMID- 9772032
TI  - Electrogastrography: a seductive promise, only partially kept.

PMID- 9772033
TI  - Ablation therapy of Barrett's esophagus: measures of success and failure.

PMID- 9772034
TI  - Helicobacter pylori and gastroesophageal reflux disease: the bug may not be all
      bad.
AB  - Peptic ulcer disease and gastric cancer of the antrum and body have been
      declining in the 20th century. In contrast, a new group of diseases are
      increasingly rapidly in Western countries: gastroesophageal reflux disease,
      Barrett's esophagus, and adenocarcinoma of the distal esophagus. Recent studies
      suggest this phenomenon may be related to the simultaneous fall in the prevalence
      of Helicobacter pylori (H. pylori) colonization, especially by the virulent cagA
      + strains. H. pylori infection with the cagA+ strain is potentially protective
      against the spectrum of gastroesophageal reflux disease because it lowers
      intragastric acidity as the result of a pangastritis, frequently with multifocal
      gastric atrophy and possibly increased intragastric ammonia production. Assuming
      that some types of H. pylori strains are protective, our entire approach to the
      worldwide elimination of this organism, sometimes indiscriminately, will need
      critical reevaluation.

PMID- 9772035
TI  - Gastric myoelectrical activity in patients with gastric outlet obstruction and
      idiopathic gastroparesis.
AB  - OBJECTIVE: The cause of gastroparesis may be uncertain in some patients.
      Mechanical obstruction of the stomach or duodenum should be excluded in patients
      with idiopathic gastroparesis. The objective of this study was to compare gastric
      myoelectrical activity in patients with idiopathic gastroparesis with that of
      patients with gastroparesis due to mechanical obstruction of the stomach or
      duodenum. METHODS: Electrogastrography techniques were used to record gastric
      myoelectrical activity in 20 patients with idiopathic gastroparesis and in nine
      patients with gastroparesis secondary to gastric outlet obstruction. Four of
      these nine patients initially were thought to have idiopathic gastroparesis.
      Electrogastrograms (EGGs) were recorded from 29 healthy subjects who served as
      controls. EGGs were recorded for 20-30 min 2 h after a standard 200-Kcal meal and
      were analyzed visually and by computer. RESULTS: Patients with gastroparesis due
      to outlet obstruction had high-amplitude and excessively regular 3-cycles-per
      minute (cpm) EGG patterns, whereas patients with idiopathic gastroparesis had
      primarily 1- to 2-cpm patterns and little 3-cpm EGG activity. The percentage of
      total EGG power in the 3-cpm range was approximately 50% in patients with gastric
      outlet obstruction compared with 20% in patients with idiopathic gastroparesis (p
      < 0.001). The percentage of EGG power in the normal 3-cpm range was greater in
      the obstructed patients (50%) than in the healthy controls (35%; p < 0.052).
      CONCLUSIONS: Gastric myoelectrical patterns recorded in the EGG distinguish
      mechanical and idiopathic causes of gastroparesis and may be useful in evaluating
      patients with nausea, vomiting, and gastroparesis of unknown cause.

PMID- 9772036
TI  - Restoration of the normal squamous lining in Barrett's esophagus by argon beam
      plasma coagulation.
AB  - OBJECTIVE: Barrett's esophagus is associated with significantly increased risk of
      development of esophageal adenocarcinoma. Replacing columnar epithelium with the
      normal squamous lining in this condition offers the possibility of decreasing the
      risk of degeneration to invasive adenocarcinoma. This study aimed to establish
      the feasibility of argon beam plasma coagulation (ABPC), in conjunction with
      control of gastroesophageal reflux, to restore the squamous lining. METHODS:
      Thirty patients with Barrett's esophagus (four low-grade dysplasia, three high
      grade) were recruited from our surveillance program, and underwent endoscopic
      ABPC. RESULTS: Twenty-seven patients completed treatment, with macroscopic
      replacement of their columnar lining by squamous epithelium, histologically
      confirmed in all 27, and followed up for a median of 9 months (range, 6-18
      months). Two patterns of squamous replacement were identified: 70% of patients
      showed squamous epithelium with no persistent intestinal metaplasia, and in 30%
      the new squamous epithelium covered areas of underlying intestinal metaplasia.
      One patient has withdrawn from the study. Two esophageal perforations, with one
      death, occurred early in the study. CONCLUSION: ABPC, in conjunction with control
      of gastroesophageal reflux, allows squamous regrowth in both benign and
      dysplastic Barrett's esophagus. Despite the theoretical safety advantages of ABPC
      over techniques such as laser, esophageal perforation may occur with this
      technique. It is too soon to recommend ABPC for dysplastic or nondysplastic
      Barrett's because follow-up is too short to show a decreased incidence of and
      mortality from adenocarcinoma.

PMID- 9772037
TI  - Prevalence of gastrointestinal symptoms in a multiracial Asian population, with
      particular reference to reflux-type symptoms.
AB  - OBJECTIVE: Data on the epidemiology of chronic gastrointestinal symptoms in the
      East are limited. The aims of this study were to estimate the prevalence of
      chronic gastrointestinal symptoms in Singapore and to determine whether ethnic
      differences in the prevalence of these symptoms exist. METHODS: A cross-sectional
      survey, using a reliable and valid questionnaire, was carried out in a race
      stratified random sample of residents aged 21-95 yr (mean+/-SD, 40+/-1 yr) in a
      Singaporean town; 93% responded (n=696). RESULTS: The ethnic-adjusted prevalence
      of chronic abdominal pain, frequent dyspepsia, irritable bowel syndrome, chronic
      constipation, chronic diarrhea, and frequent reflux were 5.7% (95% confidence
      interval [CI], 3.3-8.1), 7.9% (95% CI, 5.0-10.8), 2.3% (95% CI, 0.8-3.9), 3.9%
      (95% CI, 1.9-5.9), 4.5% (95% CI, 2.3-6.7), and 1.6% (95% CI, 0.6-2.6),
      respectively. There were no ethnic differences in the prevalence of any of these
      symptom categories except for reflux-type symptoms, which were more common among
      Indians (7.5%; 95% CI, 4.4-11.7) than Chinese (0.8%; 95% CI, 0.1-3.0) or Malays
      (3.0%; 95% CI, 1.26.1). CONCLUSION: The prevalence of all types of chronic
      gastrointestinal symptoms in the general population of Singapore was low compared
      with those in the West. Chronic gastrointestinal symptoms were equally prevalent
      in the three major ethnic groups except for reflux-type symptoms, which were more
      common among Indians than Chinese or Malays.

PMID- 9772038
TI  - Involvement of cholecystokininA receptors in transient lower esophageal sphincter
      relaxations triggered by gastric distension.
AB  - OBJECTIVE: Transient lower esophageal sphincter relaxations (TLESRs) are the main
      mechanism underlying gastroesophageal reflux. In the present study we evaluated
      the effect of loxiglumide, a specific cholecystokininA (CCKA)-receptor
      antagonist, on the occurrence of TLESRs evoked by gastric distension. METHODS:
      Eight healthy subjects underwent esophageal manometry using a 10-lumen sleeve
      assembly during placebo or loxiglumide (10 mg/kg/h) in a randomized double-blind
      order. Gastric distension was induced by inflation of 400 ml of air. RESULTS:
      Basal lower esophageal pressure (LESP) and swallow-induced relaxation were not
      affected by loxiglumide. Loxiglumide significantly reduced the number of TLESRs,
      from 11.5 (5.8-18.3) to 6.0 (3.3-14.3) during the total recording period of 1 h,
      and from 5.5 (4.25-7.5) to 2.0 (0.5-6.8) during the first 15 min. The number of
      common cavities was significantly decreased by loxiglumide, from 8.0 (4.0-20.0)
      to 5.0 (2.0-7.8). TLESRs represented the main mechanism (60% during placebo, 74%
      during loxiglumide) underlying common cavities, followed by swallow-induced
      relaxation. CONCLUSIONS: Loxiglumide significantly reduces the number of TLESRs
      triggered by gastric distension without interfering with swallow-related
      relaxation of the lower esophageal sphincter, suggesting the involvement of CCKA
      receptors in the reflex pathway mediating TLESRs.

PMID- 9772039
TI  - Palliation of malignant esophageal obstruction due to intrinsic and extrinsic
      lesions with expandable metal stents.
AB  - OBJECTIVE: Metal stents have become the standard of care for esophageal stenting.
      The aim of this study was to determine the safety and efficacy of metal stents
      for the palliation of dysphagia caused by extraesophageal malignancies
      compressing the esophagus, compared with that caused by intrinsic lesions
      involving the esophagus. METHODS: Expandable metal stents were placed in 46
      consecutive patients with dysphagia caused by malignant extrinsic compression of
      the esophagus (n=24) and intrinsic esophageal strictures (n=22). Quality of life
      was determined by a dysphagia score and the Karnofsky performance scale. Patients
      were followed until death. RESULTS: Stents were successfully deployed in all 24
      patients. Dysphagia scores improved from a median of 3 (range, 3-4; mean, 3.5+/
      0.2) to a median of 2 (range, 1-4; mean, 1.6+/-0.4; p < 0.0001) in the extrinsic
      group, and from a median of 3 (range, 2-4) to a median of 1 (range, 1-3) in the
      intrinsic group (p < 0.0001). The improvement was significantly greater (p=0.01)
      in the intrinsic group. There was no significant difference in the Karnofsky
      score between the two groups. CONCLUSIONS: Patients with intrinsic lesions have
      better palliation of dysphagia than those with extrinsic lesions. Future studies
      with other study designs will need to consider this.

PMID- 9772040
TI  - The utility of liver function test abnormalities concomitant with biliary
      symptoms in predicting a favorable response to endoscopic sphincterotomy in
      patients with presumed sphincter of Oddi dysfunction.
AB  - OBJECTIVES: We sought to study the utility of liver function test abnormalities
      concomitant with biliary symptoms in predicting a favorable response to
      endoscopic sphincterotomy in patients with Geenen class II sphincter of Oddi
      dysfunction. METHODS: We reviewed the clinical course and liver function test
      results of 24 Geenen-Hogan class II postcholecystectomy patients with biliary
      colic secondary to sphincter of Oddi dysfunction who did not undergo sphincter of
      Oddi manometry before treatment with endoscopic sphincterotomy. RESULTS: Twenty
      of the 24 patients had an average of 1.4 episodes of abnormal liver function
      tests associated with biliary colic; eight patients had dilated common bile duct
      on cholangiogram. Eighteen of the 20 patients with abnormal liver function tests
      (90%) were pain-free after sphincterotomy; in contrast, only one of four patients
      (25%) without liver function test changes responded to sphincterotomy. Fisher
      exact analysis showed that abnormal liver function tests was a significant
      predictor for favorable response to sphincterotomy with a two-tail p value of
      0.018. Of the eight patients with bile duct dilatation, six (75%) responded
      favorably to sphincterotomy, whereas 13 of 16 patients (81%) without dilatation
      also responded to sphincterotomy. Analysis of common bile duct dilatation as a
      predictive factor showed no significance (p=1.00). CONCLUSIONS: We conclude that
      the occurrence of abnormal liver function tests during biliary colic may be used
      to select patients for endoscopic sphincterotomy. Sphincter of Oddi manometry may
      not be needed in these cases.

PMID- 9772041
TI  - Comparison of duodenal with jejunal biopsy and aspirate in chronic human
      immunodeficiency virus-related diarrhea.
AB  - OBJECTIVES: In human immunodeficiency virus (HIV)-infected patients with chronic
      unexplained diarrhea, upper endoscopy with small bowel biopsy and aspirate is
      often performed to identify treatable pathogens. The purpose of this study was to
      compare the diagnostic yield of duodenal with jejunal biopsy and aspirate.
      METHODS: All HIV-infected patients with chronic unexplained diarrhea who were
      evaluated by upper endoscopy at Bellevue Hospital Center between January 1992 and
      January 1997 were identified. Data were collected by reviewing patient charts,
      endoscopy reports, and pathology records. RESULTS: During the 5-yr study period,
      442 patients underwent upper endoscopy with sampling of the duodenum (N=173) or
      jejunum (N=269). A pathogen was identified in 123 patients (27.8%). Microsporidia
      was the most common organism detected (12.2%). The diagnostic yield of jejunal
      biopsy and aspirate was significantly higher than that obtained from the duodenum
      (32.3% vs 20.8%, p=0.009). Small bowel aspirates detected a pathogen in only 1.8%
      of patients evaluated, and there was no difference in the yield of duodenal and
      jejunal aspirates (1.3% vs 2.1%, p=0.7). Patients with a CD4 count of < 100
      cells/mm3 were significantly more likely to have a pathogen identified than those
      with higher CD4 counts (38.8% vs 7.1%,p < 0.0001). CONCLUSIONS: Upper endoscopy
      with small bowel biopsy and aspirate identifies a pathogen in 27.8% of
      individuals with HIV-related chronic unexplained diarrhea. In this patient
      population, jejunal biopsies acquired by enteroscopy are superior to those
      obtained from the duodenum. Small bowel aspirates are of little value in the
      workup of chronic HIV-related diarrhea.

PMID- 9772042
TI  - The interrelationship between Helicobacter pylori vacuolating cytotoxin and
      gastric carcinoma.
AB  - OBJECTIVE: We aimed to determine whether cytotoxin-positive Helicobacter pylori
      strains are associated with gastric carcinoma. METHODS: We studied 130 patients:
      57 H. pylori-positive patients with gastric carcinoma, 53 H. pylori-positive
      patients without gastric carcinoma, and 20 H. pylori-negative subjects. The
      ability of H. pylori strains to produce vacuolating cytotoxin was tested in INT
      407 and HeLa cells. The presence of antibodies to cytotoxin was investigated in
      blood serum from all subjects by immunoblotting. Fragments of the gastric mucosa
      from patients without gastric carcinoma and H. pylori-negative subjects were
      obtained for histopathological study. RESULTS: Considering the results as a
      whole, 40 (70.2%) patients with and 22 (41.5%) without gastric carcinoma were
      colonized by cytotoxin-positive strains. Antibodies against cytotoxin were not
      observed in the serum from 17 (29.8%) gastric carcinoma patients and from 31
      (58.5%) patients without gastric carcinoma. H. pylori strains isolated from these
      patients did not produce cytotoxin in vitro. In regard to cytotoxin positivity, a
      significant difference was observed between patients with and without gastric
      carcinoma (p=0.004; odds ratio [OR]: 3.3; 95% confidence interval [CI]: 1.4-7.9).
      Higher scores of mononuclear (p=0.0001) and polymorphonuclear (p=0.000003) cells
      were observed in the antral mucosa from H. pylori-positive patients without
      gastric carcinoma infected by cytotoxin-positive strains than in those harboring
      cytotoxin-negative strains. CONCLUSION: Cytotoxin-producing H. pylori strains
      were more frequently observed in patients with gastric carcinoma and this aspect
      emphasizes the role of cytotoxin in the genesis of the tumor.

PMID- 9772043
TI  - Influence of topically and systemically active steroids on circulating leukocytes
      in Crohn's disease.
AB  - OBJECTIVE: Budesonide, although only topically active, is effective in the
      treatment of Crohn's disease. This study was performed to compare the clinical
      efficacies of budesonide and prednisolone in relation to the activation status of
      circulating leukocytes. METHODS: Twenty-four patients with active Crohn's disease
      were randomized to treatment with either budesonide or 6-methylprednisolone.
      Clinical response was monitored by the Crohn's disease activity index, C-reactive
      protein, and orosomucoid. Expression of CD25 and CD71 on T cells and CD64 on
      neutrophils was determined by flow cytometry. The release of TNF-alpha and IL
      1beta by peripheral blood mononuclear cells was measured by ELISA. RESULTS: After
      2 wk of treatment a clinical response was observed in both groups, but it was
      more accentuated in patients treated with prednisolone. At baseline an
      upregulation of CD71 and CD64, but not CD25, was found in active patients.
      Prednisolone significantly decreased the expression of CD64 and the release of
      TNF-alpha and IL-1beta, but did not alter the expression of CD25 and CD71.
      Budesonide treatment failed to exert any effect on circulating leukocytes.
      CONCLUSIONS: The inability of budesonide to downregulate activated circulating
      leukocytes may contribute to the somewhat lower clinical efficacy of this topical
      steroid in the treatment of active Crohn's disease.

PMID- 9772044
TI  - Circulating L-selectin levels and endothelial CD34 expression in inflammatory
      bowel disease.
AB  - OBJECTIVE: Soluble L-selectin (sL-selectin) concentrations are positively
      correlated with disease activity in ulcerative colitis (UC) but not in Crohn's
      disease (CD). This difference in sL-selectin regulation could be due to a disease
      specific regulation of L-selectin ligands. The aim of this study was to compare
      levels of circulating sL-selectin, expression of the L-selectin ligand CD34 in
      the affected colon, and inflammatory bowel disease activity. METHODS: Twenty
      three patients with UC, 16 patients with CD, and 18 control subjects were
      included in the study. In blood samples concentrations of serum sL-selectin were
      determined by an ELISA technique. In colonoscopically obtained biopsies, CD34
      expression was evaluated by immunohistochemical methods using monoclonal CD34
      antibodies. Disease activity was determined by a clinical semiquantitative scale.
      RESULTS: sL-selectin levels were found to be significantly increased along with
      increasing disease activity in UC (p < 0.001) but not in CD (p > 0.05) patients.
      UC patients with quiescent and severe disease activity had significantly lower (p
      < 0.005) and higher (p < 0.002) sL-selectin concentrations than controls,
      respectively. CD34 expression was found to be increased in both disease groups as
      compared with controls (p < 0.05). CONCLUSION: A disease-specific regulation of
      CD34 was not found as an explanation for the distinction in sL-selectin
      regulation. In the light of recent reports on low sL-selectin in other diseases,
      it is suggested instead that ongoing neutrophil activation may be the reason for
      low sL-selectin concentrations during quiescent disease stages, whereas chemokine
      secretion could explain the increased levels of sL-selectin associated with
      severe disease activity.

PMID- 9772045
TI  - Steroid-unresponsive acute attacks of inflammatory bowel disease:
      immunomodulation by tacrolimus (FK506).
AB  - OBJECTIVE: Steroid treatment failure in acute Crohn's disease and ulcerative
      colitis frequently necessitates surgical intervention. Several alternative
      therapeutic strategies have been raised. The most promising so far has been
      intravenous cyclosporine, but the results in the long term have been
      discouraging. We assessed the efficacy and safety of the new macrolide
      immunomodulator tacrolimus as an alternative to cyclosporine A. METHODS: Eleven
      patients with steroid-refractory disease (six ulcerative colitis, two
      indeterminate colitis, two Crohn's disease, one pouchitis) and severe activity
      according to the Truelove and Witts criteria or Crohn's disease activity index >
      150, respectively, were eligible for the study. All patients were treated with
      intravenous tacrolimus for 7-10 days followed by oral treatment over a median
      period of 7 months (range 0.25-16). Azathioprine and mesalamine were given
      concomitantly. Steroids were tapered according to clinical activity. RESULTS:
      Seven of 11 patients achieved remission rapidly, whereas a modest improvement was
      noted in two. Only two patients required an early and one a delayed colectomy.
      Moreover, a rectovaginal fistula closure in a case of Crohn's disease and an
      improvement of pouchitis was observed. A tapering to low dose steroids was
      possible during oral tacrolimus therapy in all nine responders and remission was
      maintained in five of them (mean follow-up 9.2 months). The drug was well
      tolerated and side effects were managed conservatively. CONCLUSION: Tacrolimus
      induced rapid remission in steroid resistant inflammatory bowel disease in the
      majority of cases. It appears to be an effective treatment modality that may be
      superior to cyclosporine with respect to maintenance of remission.

PMID- 9772046
TI  - The menstrual cycle and its effect on inflammatory bowel disease and irritable
      bowel syndrome: a prevalence study.
AB  - OBJECTIVE: Female patients with bowel disease commonly report worsening symptoms
      in relation to the menstrual cycle. Our aim was to determine the nature of
      gastrointestinal symptoms correlating with the menstrual cycle in women with
      inflammatory and irritable bowel disease. METHODS: This was a retrospective study
      involving 49 women with ulcerative colitis (UC), 49 women with Crohn's disease
      (CD), 46 women with irritable bowel syndrome (IBS), and 90 healthy community
      controls. Participants were interviewed using a questionnaire including
      information regarding general health, medication history, pregnancy, as well as
      premenstrual and menstrual symptoms. Chi2 testing and logistic regression
      modeling were used to test for differences in frequencies between groups and for
      risk analysis. RESULTS: Premenstrual symptoms were reported by 93% of all women
      but statistically more often by patients with CD (p < 0.01). CD patients were
      also more likely to report increased gastrointestinal symptoms during
      menstruation ( < 0.01), diarrhea being the symptom reported most often. All
      disease groups had a cyclical pattern to their bowel habits significantly more
      than controls (p=0.01). Cyclical symptoms included diarrhea, abdominal pain, and
      constipation. Logistic regression revealed an odds ratio (OR) of 1.1 (95% CI 0.9
      1.2) for experiencing bowel symptoms during the premenstrual and menstrual phases
      and an OR of 2.0 (95% CI 1.2-3.2) for experiencing a cyclical pattern in bowel
      habit changes in women with bowel disease. CONCLUSION: The prevalence of
      menstrually related symptoms is high, and appears to affect bowel patterns. The
      physiological and clinical effects of the menstrual cycle should be taken into
      consideration when assessing for disease activity.

PMID- 9772047
TI  - Clostridium difficile colitis: factors influencing treatment failure and relapse-
      a prospective evaluation.
AB  - OBJECTIVE: The aim of this study was to identify patient related factors that may
      influence the treatment response and relapse following Clostridium difficile (C.
      difficile) colitis. METHODS: A total of 36 patients with C. difficile colitis
      were followed for 3 months. Age, sex, place of residence, severity of infection,
      treatment, underlying medical condition, and treatment were compared in patients
      who failed to respond to treatment in 14 days and in patients who relapsed after
      a successful treatment. Student's t test and Fisher's exact test were used to
      compare the groups. A p value of <0.05 was considered significant. RESULTS: A low
      serum albumin (p=0.016) and continuation of systemic antibiotic treatment were
      found to be associated with refractoriness to treatment. Continuation or
      restarting of antibiotics after successful treatment increases the risk of
      relapse (p=0.003). The age, sex place of residence, underlying medical condition,
      and type of precipitating antibiotics had no effect on the treatment response and
      relapse. The severity of colitis and the type of therapy (metronidazole vs
      vancomycin) did not influence the treatment response or relapse. CONCLUSION: Low
      serum albumin serves as a useful marker for patients who require prolonged
      treatment for C. difficile colitis. It is prudent to review the need for the
      continuation of systemic antibiotic treatment, as it adversely affects the
      treatment response and increases the risk of relapse.

PMID- 9772048
TI  - Noninvasive estimate of bile flux through the gallbladder in humans.
AB  - OBJECTIVE: The aim of this study was to assess whether a single noninvasive
      technique, ultrasonography, is able in vivo: 1) to evaluate the time-related
      patterns of gallbladder bile storage and emptying, and 2) to quantitate the
      amount of bile flux through the gallbladder (GB). METHODS: Healthy volunteers
      were submitted to the simultaneous assessment of gallbladder volume variations by
      frequent serial ultrasonographic (US) measurements and of hepatic bile flow
      through the GB by quantitative cholescintigraphy (QC) during continuous i.v.
      infusion of 99 mTc-HIDA. An ad hoc mathematical analysis of US GB volume
      measurements was used to estimate the amount of bile flux through the GB. The QC
      derived measurements of the flux of hepatic bile through the GB was used to
      substantiate the US-derived estimates. RESULTS: The curves expressing the time
      related GB handling of hepatic bile obtained independently from US and QC
      measurements were statistically equivalent, and both techniques showed that the
      patterns and the amount of hepatic bile handled by the gallbladder after meal
      ingestion is remarkably different during three successive phases. After meals,
      hepatic bile was mainly 1) stored in the GB in the first phase; 2) emptied from
      the GB in a second phase; and 3) stored in the GB in the third phase. The
      ultrasonographic analysis estimated that 1) 23.8+/-12.5 ml (0.44+/-0.11 ml/min),
      5.1+/-3.9 ml (0.15+/-0.10 ml/min), and 33.2+/-10.5 ml (0.53+/-0.16 ml/min) of
      hepatic bile entered into the GB during the three successive postprandial phases,
      and 2) the entire amount of bile flowing bidirectionally through the cystic duct,
      during the observation period (132.6+/-23.3 ml) was about five-fold greater than
      that estimated by the usually employed variables. CONCLUSION: The proposed
      mathematical analysis of frequent ultrasonographic measurements of the GB volumes
      enables one to estimate noninvasively the flux of bile through the gallbladder in
      humans.

PMID- 9772049
TI  - Magnetic resonance cholangiography using half-Fourier acquisition for diagnosing
      choledocholithiasis.
AB  - OBJECTIVE: Magnetic resonance cholangiography (MRC), using a half-Fourier
      acquisition single-shot turbo spin-echo (HASTE) sequence, noninvasively provides
      very rapid (1-2 s) and high-quality images of the biliary tract. We assessed the
      diagnostic usefulness of HASTE-MRC for choledocholithiasis. METHODS: A total of
      101 patients with suspected choledocholithiasis underwent MRC, ultrasonography,
      and endoscopic retrograde cholangiopancreatography (ERCP). In 97 patients in whom
      ERCP fully depicted the common bile duct, we retrospectively analyzed the
      capability of MRC to image the common bile duct and to diagnose
      choledocholithiasis, in comparison with that of ultrasonography. RESULTS: In 34
      patients, ERCP demonstrated bile duct stones, which were confirmed at endoscopic
      or surgical treatment. The common bile duct was fully delineated in 98% by MRC
      and in 70% by ultrasonography. MRC (91%) was more sensitive than ultrasonography
      (71%) for detecting choledocholithiasis (p < 0.05). MRC demonstrated bile duct
      stones in all patients with stones > or =11 mm but missed calculi in the 29% of
      patients with small (3-5 mm) stones. MRC was capable of detecting
      choledocholithiasis regardless of bile duct caliber. The specificity of MRC
      (100%) was higher than that of ultrasonography (95%). CONCLUSION: HASTE-MRC, a
      fast and noninvasive procedure, can accurately diagnose choledocholithiasis
      although the detectability for small stones is limited.

PMID- 9772050
TI  - Transjugular intrahepatic portosystemic shunt (TIPS) in patients with refractory
      ascites: effect on body weight and Child-Pugh score.
AB  - OBJECTIVE: This study suggests that patients with medically refractory ascites
      treated with transjugular intrahepatic portosystemic shunt (TIPS) may have
      improved in overall clinical status. METHODS: We performed a retrospective study
      of 35 patients with medically refractory ascites treated with TIPS. Body weight,
      ascites, and Child-Pugh score were assessed at baseline, at 2 months, and after a
      mean 8.8-month follow-up interval. RESULTS: After TIPS, there was significant
      improvement in Child-Pugh score from 9.7+/-1.5 to 8.2+/-2.3. Ascites completely
      resolved or improved in 23 of 24 patients (96%) who had long term follow-up. Two
      months after TIPS, there was a significant decrease in weight of 6.1 kg
      corresponding to a loss of ascites. Between 2 and 8.8 months, there was a
      significant mean weight gain of 5.5 kg. CONCLUSION: This study suggests that
      patients treated with medically refractory ascites with TIPS may have improvement
      in overall clinical status, as measured by increase in lean body mass and
      improvement in Child-Pugh score.

PMID- 9772051
TI  - A cost analysis of long term antibiotic prophylaxis for spontaneous bacterial
      peritonitis in cirrhosis.
AB  - OBJECTIVE: The aim of this study was to perform a cost analysis of different
      strategies of long term antibiotic prophylaxis for spontaneous bacterial
      peritonitis (SBP) in patients with cirrhosis and ascites. The study involved a
      cost analysis using a decision analysis model and patients with cirrhosis and
      ascites who are at risk for developing SBP. METHODS: Two different strategies of
      antibiotic prophylaxis were compared with a "no prophylaxis" strategy in patients
      with cirrhosis and ascites using a decision analysis model. In strategy I,
      antibiotic prophylaxis was administered in all patients with cirrhosis and
      ascites and in strategy II, patients were stratified into a low risk and a high
      risk group on the basis of serum bilirubin and ascitic fluid protein levels; only
      patients in the high risk group received antibiotic prophylaxis. The cost per
      patient treated for 1 yr was the outcome measure compared in the different
      strategies. Clinical input probabilities and ranges used were obtained by
      searching the MEDLINE database for English language articles. Cost estimates were
      obtained from a university hospital setting. Cost analysis was done with a
      societal perspective, and only direct costs were taken into account. Sensitivity
      analyses were performed to evaluate the effect of variations in the key clinical
      probabilities and cost estimates ranging from a best case to a worst case
      scenario on the outcome measure. RESULTS: The estimated cost per patient treated
      in strategy I, strategy II, and strategy III (the strategy of "no prophylaxis")
      were $1311, $1123, and $3509, respectively. Over a broad range of clinical and
      cost variables, the strategy of risk stratification and restriction of antibiotic
      prophylaxis to the subgroup of patients with cirrhosis and ascites who were at
      high risk for SBP (as identified by serum bilirubin >2.5 mg/dl and ascitic fluid
      protein <1 g/dl) was the most favored strategy. However, when the cost of
      prophylaxis was low or the probability of a primary episode of SBP was at the
      lower end of the range reported in the literature, administering antibiotic
      prophylaxis to all patients with cirrhosis and ascites was the least costly
      strategy. CONCLUSION: This cost analysis indicates that antibiotic prophylaxis
      particularly when restricted to a subgroup of patients who, by simple laboratory
      parameters, are identified to be at high risk for SBP, is very cost-effective in
      the prevention of SBP in patients with cirrhosis and ascites.

PMID- 9772052
TI  - Lipoprotein changes in patients with chronic hepatitis C treated with interferon
      alpha.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of interferon-alpha
      therapy on the lipid profile of patients with chronic hepatitis C. METHODS: In 36
      consecutive patients with chronic hepatitis C, fasting lipoproteins were
      evaluated prospectively at baseline, 1, 3 and 6 months during interferon-alpha
      therapy and 3 months after the end of treatment. RESULTS: During interferon-alpha
      therapy, there was a progressive increase in total and very low density
      lipoprotein (VLDL)-triglycerides, VLDL-cholesterol and a sustained raise in
      apolipoprotein (apo) B. In parallel, there was a reduction in high density
      lipoprotein (HDL)-cholesterol and apo A1 levels. In contrast, total and low
      density lipoprotein (LDL)-cholesterol and lipoprotein (a) levels remained
      essentially unchanged during interferon-alpha therapy. Three patients developed
      chylomicronemia, two of them with severe hypertriglyceridemia, although none of
      them presented with pancreatitis. Chylomicronemia and severe hypertriglyceridemia
      were more common in patients with basal triglycerides above 200 mg/dl. Nineteen
      patients responded to interferon-alpha therapy, but their lipid profile did nor
      differ from that of nonresponders. Three months after the end of interferon-alpha
      therapy lipid changes subsided, although VLDL and HDL-cholesterol and apo B did
      not reach basal levels. CONCLUSION: In patients with chronic hepatitis C,
      interferon-alpha therapy is associated with an increase of total and VLDL
      triglycerides, VLDL-cholesterol and apo B, and a decline of HDL-cholesterol and
      apo A1. The development of chylomicronemia and severe hypertriglyceridemia in
      some cases makes mandatory a close monitoring of triglycerides during interferon
      alpha therapy, particularly among patients with increased triglycerides at
      baseline.

PMID- 9772053
TI  - Evaluation of hepatocyte function after extracorporeal shock wave lithotripsy
      with hepatobiliary scintigraphy.
AB  - OBJECTIVE: Extra corporeal shock wave lithotripsy is a promising and effective
      therapy mode in the nonsurgical therapy of gallstones. This prospective study was
      conducted to investigate the effects of ESWL on hepatocellular function, using
      quantitative hepatobiliary scintigraphy, serum aminotransferase, alkaline
      phosphatase (ALP), amylase (AML), and direct and indirect bilirubin levels.
      METHODS: The study consisted of 22 patients with ultrasonographically documented
      gallstones. Hepatobiliary scintigraphy was applied to all patients before ESWL
      and biochemical tests were performed. Scintigraphy and biochemical tests were
      repeated in 16 patients 24 h, in seven patients 72 h, and in six patients 1 wk
      after ESWL. The hepatic extraction fraction (HEF) was calculated using
      deconvolution analysis of scintigraphic data. RESULTS: All patients' pre-ESWL
      biochemical tests and HEF values were within the normal range. The 24- and 72-h
      post-ESWL aminotransferase, ALP, and AML levels and HEF values were significantly
      different from pre-ESWL values (p < 0.05). After 1 wk this difference
      disappeared. Decreased HEF values were observed in 50% of patients 24 h, in 71.7%
      of patients 72 h, and in 16.6% of patients 1 wk after ESWL. A direct relationship
      was also observed between the number of shocks applied and the degree of
      impairment in HEF values. CONCLUSION: Transient hepatocellular dysfunction, which
      usually occurs after ESWL, can be demonstrated and monitored using quantitative
      hepatobiliary scintigraphy.

PMID- 9772054
TI  - Safety and efficacy of rabeprazole in combination with four antibiotic regimens
      for the eradication of Helicobacter pylori in patients with chronic gastritis
      with or without peptic ulceration.
AB  - OBJECTIVES: Rabeprazole is a new fast acting proton pump inhibitor that has
      recently been proven to be effective in the treatment of peptic ulceration and
      reflux esophagitis. The aim of this study was to evaluate rabeprazole in
      combination with antibiotics for the eradication of Helicobacter pylori (H.
      pylori) in patients with chronic active gastritis with or without peptic ulcer
      disease. METHODS: Seventy-five H. pylori-infected patients were randomized in a
      double-blind fashion to receive a 7-day treatment regimen consisting of: RAC,
      RAM, RCM, or RC (R=rabeprazole 20 mg b.d., A=amoxycillin 1 g b.d.,
      C=clarithromycin 500 mg b.d., M=metronidazole 400 mg b.d.). Randomized patients
      were H. pylori-positive by gastric biopsy urease test, histology and 13C urea
      breath test (13C-UBT). H. pylori eradication was assessed by 13C-UBT, 4 and 8 wk
      after finishing treatment. Endoscopy with histology and culture for antibiotic
      sensitivity testing was performed pretreatment and if treatment failed. RESULTS:
      On an intention-to-treat analysis, treatment success was: RCM 100%, RAC 95%, RAM
      90%, and RC 63%. The most common side effects were loose stools, headache, and
      taste disturbance, but there were no serious adverse events related to the study
      medication. The two patients failing RAM treatment had metronidazole-resistant
      strains before and after treatment. None of the pretreatment H. pylori isolates
      from six patients failing RC were clarithromycin resistant, but three of five
      successfully cultured posttreatment had developed clarithromycin resistance.
      CONCLUSION: Rabeprazole-based triple therapy with two antibiotics for 1 wk is
      safe and effective in eradicating H. pylori. Dual therapy with clarithromycin is
      less successful, and the majority of treatment failures develop clarithromycin
      resistance.

PMID- 9772055
TI  - False-negative biopsy urease test in bleeding ulcers caused by the buffering
      effects of blood.
AB  - OBJECTIVES: A false-negative biopsy urease test (BUT) is common in Helicobacter
      pylori-associated bleeding peptic ulcers. Although blood in the stomach is
      thought to interfere with the biopsy urease test, the underlying mechanism
      remains unknown. This in vitro experiment sought to identify the blood
      component(s) that interfere with the biopsy urease test, and delineate the
      mechanism of inhibition. METHODS: The modified Hazell's microtiter test was used
      to detect the urease activity of H. pylori. A positive result was indicated by a
      color change of the pH indicator, bromothymol blue, at 630 nm. Human whole blood,
      sera with and without anti-H. pylori antibody, electrolytes, and enzymes were
      incubated with H. pylori to identify the blood component(s) causing the
      inhibition of urease activity. In addition, any interference of the pH color
      indicator was tested by adding different concentrations of serum albumin to the
      urease reagent that contained a fixed quantity of ammonia in the absence of H.
      pylori. RESULTS: The color change of the microtiter urease test was significantly
      reduced by blood (p < 0.0001), regardless of the presence of anti-H. pylori
      antibody. Electrolytes and serum enzymes did not interfere with the urease test.
      The color change of the pH indicator was progressively suppressed by higher
      concentrations of serum albumin. CONCLUSIONS: Blood adversely affects the
      performance of the BUT. This is mediated by the buffering effect of serum albumin
      on the pH indicator, rather than by a direct inhibition on the urease activity.

PMID- 9772056
TI  - Cure of Helicobacter pylori infection and healing of duodenal ulcer: comparison
      of pantoprazole-based one-week modified triple therapy versus two-week dual
      therapy. The International Pantoprazole HP Study Group.
AB  - OBJECTIVE: Eradication of Helicobacter pylori (H. pylori) is recommended as the
      first-line therapeutic concept for reliable long-term prevention of duodenal
      ulcer (DU) relapse. Current treatment regimens vary in efficacy, complexity, and
      compliance. To assess the efficacy of pantoprazole in H. pylori eradication in
      parallel groups of patients using two eradication regimens. METHODS: Patients,
      (18-85 yr old; intention-to-treat, n=286) with proven DU, positive rapid urease
      test (biopsy), and 13C-urea breath test (UBT) were included in a prospective,
      randomized, multicenter study. Modified triple therapy consisted of 40 mg
      pantoprazole b.i.d., 500 mg clarithromycin t.i.d., and 500 mg metronidazole
      t.i.d. for 7 days (PCM therapy); dual therapy consisted of 40 mg pantoprazole
      b.i.d. and 500 mg clarithromycin t.id. for 14 days (PC therapy). In both groups
      40 mg pantoprazole o.d. was given until day 28 when healing of DU was evaluated
      endoscopically; H. pylori status was assessed by UBT on day 56. RESULTS: H.
      pylori eradication rate was 95% in PCM versus 60% in PC therapy groups
      (perprotocol population, p < 0.001), and 82% in PCM versus 50% in PC therapy in
      the intention-to-treat patient population (p < 0.001). The DU healing rate was
      98% in the PCM and 95% in the PC therapy groups (per-protocol population). Both
      regimens were similarly well tolerated. Adverse events in both regimens included
      taste disturbance, diarrhea, and increased serum concentration of liver enzymes,
      at an incidence of < 10%. CONCLUSIONS: Compared to 2-wk PC therapy (pantoprazole
      and clarithromycin), the 1-wk PCM therapy (pantoprazole, clarithromycin, and
      metronidazole) is a significantly superior and highly promising strategy for
      eradication of H. pylori.

PMID- 9772057
TI  - Superior mesenteric artery impedance in chronic liver diseases: relationship with
      disease severity and portal circulation.
AB  - OBJECTIVE: The increase of splanchnic blood flow volume in liver cirrhosis is
      attributed to decreased arterial resistance. The aim of this study was to
      noninvasively investigate superior mesenteric artery impedance in patients with
      chronic liver diseases and to assess its relationship with portal hemodynamics
      and with clinical parameters. METHODS: Superior mesenteric artery (SMA)
      pulsatility (SMA-PI) and resistance (SMA-RI) indices and portal vein flow
      parameters (velocity, volume, and congestion index) were measured by duplex
      Doppler ultrasound in 14 patients with chronic hepatitis, in 73 cirrhotics, in 30
      liver transplant recipients, and in 31 control subjects. RESULTS: SMA-PI
      significantly differed among the five groups (p < 0.0001), being lower in
      cirrhotics (2.55+/-0.70) and transplanted patients (2.77+/-0.69) than in chronic
      hepatitis (3.28+/-0.57) and control subjects (3.42+/-0.92). SMA-PI was lower in
      ascitic cirrhosis (2.40+/-0.71) than in compensated cirrhosis (2.71+/-0.70) (p <
      0.01) and in cirrhotics with large varices (2.30+/-0.67) than in those without
      varices (2.75+/-0.65) (p < 0.05). Moreover SMA-PI correlated with numeric Child
      Pugh score (r=-0.28) and portal vein congestion index (r=-0.36). CONCLUSION:
      Hyperdynamic splanchnic circulation, noninvasively assessed by a decrease of
      mesenteric artery impedance, occurs in cirrhosis since the early stage of the
      disease and tends to worsen in relation to liver failure and the severity of
      portal hypertension. Furthermore, the persistent SMA-PI decrease in transplant
      recipients suggests a consistent contribution to this circulatory alteration from
      a patent portosystemic collateral circulation.

PMID- 9772059
TI  - Percutaneous endoscopic gastrostomy to treat upside-down stomach before stent
      insertion in a patient with distal esophageal carcinoma.
AB  - A 89-yr-old woman presenting with dysphagia due to an obstructing adenocarcinoma
      of the distal esophagus was additionally diagnosed to have an upside-down stomach
      creating a sharp angulation at the esophagogastric junction. Gastric anatomy had
      to be restored before palliative stent insertion. As the patient was judged unfit
      for surgery, the stomach was repositioned endoscopically and fixed to the
      abdominal wall by percutaneous endoscopic gastrostomy. In the same sitting, a
      metal stent was placed. Effective palliation of dysphagia was achieved until the
      patient died of an unrelated cause 5 months later.

PMID- 9772058
TI  - A case of syncytial giant cell hepatitis with features of a paramyxoviral
      infection.
AB  - Adult syncytial giant cell hepatitis (GCH) is an uncommon and often fulminant
      form of hepatitis that may be caused by infection with a novel paramyxo-like
      virus. We present the case of a 69-yr-old man who presented with acute, community
      acquired hepatitis and chronic lymphocytic leukemia. A liver biopsy showed the
      typical findings of panlobular syncytial giant cell hepatitis. Electron
      microscopic examination demonstrated abundant nucleocapsid-like protein material
      in the cytoplasm and nuclei of affected hepatocytes. These structures were
      similar to, but distinct from, those of known paramyxoviridae, suggesting
      infection with a novel, related virus. In situ hybridization studies with a probe
      directed against the measles fusion protein gene gave a positive signal with a
      hepatocyte distribution. No signal was obtained with the measles nucleocapsid
      protein probe, suggesting that the disease agent was genetically distinct from,
      but related to, the measles virus. Subsequent liver biopsies were characterized
      by the gradual disappearance of the giant cell changes and by the concomitant
      development of cirrhosis. This is a case of adult GCH that resolved spontaneously
      and led to cirrhosis, thus implicating GCH as a potential cause of "cryptogenic"
      liver disease. Our findings provide further support for the existence of a
      distinct, as yet unidentified viral species as a cause of this disease.

PMID- 9772061
TI  - Multimodality treatment for gastric carcinoid tumor with liver metastases.
AB  - Carcinoid tumors are the most common neuroendocrine tumors in the
      gastrointestinal tract, and between 10% and 30% of these tumors are gastric in
      origin. Three types of gastric carcinoid tumors are recognized: type I,
      associated with chronic atrophic gastritis type A; type II, associated with
      multiple endocrine neoplasia; and type III, sporadic and the most malignant. We
      present a patient with an aggressive, sporadic-type gastric carcinoid that
      metastasized to the liver. Her symptomatic treatment included the somatostatin
      analog octreotide. Octreotide scintigraphy demonstrated that this tumor avidly
      bound the peptide. The patient's gastric carcinoid (assessed by endoscopy and
      endoscopic ultrasound) regressed and she underwent hepatic artery embolization
      for her liver metastases. After initial partial CT resolution the tumor grew,
      compressing the inferior vena cava. The patient underwent orthotopic liver
      transplant with excellent recovery, although she was subsequently found to have
      two small lung metastases. She has responded well to adjuvant Indium-111
      octreotide receptor targeted therapy. This case highlights the therapeutic
      options for metastatic neuroendocrine tumors, including liver transplantation and
      adjuvant receptor targeted therapy.

PMID- 9772060
TI  - Listeria infection after liver transplantation: report of a case and review of
      the literature.
AB  - Listeria monocytogenes is a well-recognized cause of bacteremia and meningitis in
      immunocompromised individuals, including recipients of solid organ transplants,
      but has only rarely been reported following orthotopic liver transplantation
      (OLT). Most previously reported cases of listeriosis occurred months to years
      following liver transplantation; we describe a case of listeriosis that occurred
      within 1 wk of liver transplantation, shortly after discontinuation of
      trimethoprim-sulfamethoxazole prophylaxis, and review the English literature on
      Listeria infection after OLT. The patient developed abdominal pain and fever that
      suggested a bile leak, but was definitively diagnosed with Listeria infection by
      blood culture. The infection was successfully treated with 3 wk of intravenous
      ampicillin. We conclude that serious systemic infection with Listeria
      monocytogenes is uncommon following OLT, may occur early in the postoperative
      period, and responds well to treatment with high dose ampicillin.

PMID- 9772062
TI  - Sarcoidosis presenting as granulomatous colitis.
AB  - Sarcoidosis presenting solely as a granulomatous colitis is rare and appears
      identical to Crohn's disease. A 56-yr-old woman developed a Crohn's-like illness,
      which remitted after 5-ASA therapy. Two months later, she developed fever,
      adenopathy, muscle weakness, and peripheral neuropathy. A diagnosis of
      sarcoidosis was made after an extensive search for an infectious or
      rheumatological cause. This case illustrates the utility of serum angiotensin
      converting enzyme level in differentiating sarcoidosis from Crohn's disease.

PMID- 9772063
TI  - A fistula from the portal vein to the bile duct: an unusual complication of
      transjugular intrahepatic portosystemic shunt.
AB  - We describe a case of a portal vein bile duct fistula as a complication of
      transjugular intrahepatic portosystemic shunt (TIPS) placement. The patient's
      course was complicated by endocarditis, hemobilia, recurrent episodes of fever,
      and bacteremia, followed by liver transplant. The findings of fever, bacteremia
      (especially with Gram-negative organisms), and a decreased hematocrit after shunt
      placement should raise the suspicion of an infected shunt with a possible
      fistula.

PMID- 9772064
TI  - Hemophagocytic syndrome associated with fulminant ulcerative colitis and presumed
      acute pancreatitis.
AB  - We herein report a case of hemophagocytic syndrome that developed in a 25-yr-old
      man with fulminant ulcerative colitis and presumed acute pancreatitis. Physical
      examination on admission showed a chronically ill, delirious patient with an
      upper abdominal mass. Peripheral blood showed progressive pancytopenia and bone
      marrow aspirate smears revealed hypocellular bone marrow with an increase of
      histiocytes showing prominent hemophagocytosis. Plain abdominal radiography
      revealed toxic megacolon. Both ultrasound and computed tomography showed the
      enlargement of the pancreas, thus indicating presumed acute pancreatitis. No
      apparent neoplasms or viral or bacterial infections, which are normally reported
      to be the cause of hemophagocytic syndrome, were detected. The patient was
      successfully treated with high doses of prednisolone and gamma-globulin.

PMID- 9772065
TI  - Ischemic colitis and acquired resistance to activated protein C in a woman using
      oral contraceptives.
AB  - We present the case history of a 22-yr-old woman diagnosed with ischemic colitis
      associated with the use of oral contraceptives (OC). At the time of her
      presenting symptoms activated protein C (APC) resistance, a risk factor for
      thrombosis, was demonstrated. There was no laboratory evidence of inherited
      thrombophilia; that is, antithrombin III, protein C and protein S levels were
      normal and the factor V Leiden mutation was not present. The OC were discontinued
      and the patient's symptoms improved. Subsequent evaluation revealed that the
      activated protein C resistance had resolved. This case illustrates APC resistance
      as a potential link between OC use and its known association with ischemic
      colitis.

PMID- 9772066
TI  - Serous cystadenoma of the pancreas with invasive growth: benign or malignant?
AB  - We describe a case of serous cystadenoma, that invaded a lymph node and adipose
      tissue. Preoperatively, the cystic lesion of the pancreas was diagnosed as a
      serous cystadenoma and subsequently the patient, a 71-yr-old woman, underwent
      distal pancreatectomy with splenectomy. Macroscopically, a greyish white,
      externally lobulated and partly ovoid tumor, measuring 12 x 8.5 x 5 cm, occupied
      the pancreatic body and tail extensively. In cross-section, multiple nodules were
      observed, which measured from 0.5 to 3 cm in diameter, were separated by
      hyalinized fibrous septa and were filled with numerous microcysts. Light
      microscopic findings were consistent with those for serous cystadenoma. At the
      splenic hilus, the tumor was found to have invaded the lymph node and adipose
      tissue. Based on the clinicopathological features of the six reported cases,
      including the present case (which behaved in a malignant fashion in terms of
      pathological findings of invasion or metastasis), serous cystadenoma should be
      regarded as having the potential for malignant growth.

PMID- 9772067
TI  - Telomerase activity detected in pancreatic juice 19 months before a tumor is
      detected in a patient with pancreatic cancer.
AB  - We report a patient with pancreatic cancer in whom telomerase activity had been
      detected in the pancreatic juice 19 months before he was diagnosed as having
      pancreatic cancer. A 61-yr-old alcoholic man complaining of epigastric and back
      pain was diagnosed as having groove pancreatitis based on the presence of
      inflammation in the pancreatic head and its extension to the duodenal mucosa with
      an associated elevated serum amylase level. All imaging modalities showed no sign
      of a tumor. However, high telomerase activity was detected in the pancreatic
      juice collected during endoscopic retrograde pancreatography. His symptoms
      subsided due to abstinence from alcohol. A tumor, however, was recognized on
      computed tomography 19 months later, at which time the patient immediately
      underwent a pylorus-preserving pancreaticoduodenectomy. The carcinoma was located
      mainly in the Santorini duct region. High telomerase activity in the pancreatic
      juice may precede clinical detection of pancreatic cancer and thus could be a
      useful early diagnostic marker for pancreatic cancer.

PMID- 9772068
TI  - Solitary true cyst of the pancreas in two adults: analysis of cyst fluid and
      review of the literature.
AB  - Solitary true cyst of the pancreas in adults is extremely rare. We report two
      adult cases of solitary true cyst of the pancreas. In a 53-yr-old woman there was
      discovered, incidentally, a unilocular cyst of 7.0 x 6.5 cm in size in the tail
      of the pancreas that was noted on abdominal US and CT scan. A 16-yr-old boy
      presented with abdominal pain, and an abdominal US and CT scan revealed a 6.5 cm
      cystic mass located in the tail of the pancreas. Both patients underwent distal
      pancreatectomy. Histologically, the cyst was lined with flattened cuboidal and
      squamous epithelium without morphological alterations. Analysis of the cyst fluid
      revealed high CA 19-9 (>100,000 U/L) and Span-1 levels (>60,000 U/L) in both
      cases. Immunohistochemically, the lining epithelial cells of true cyst were
      positive for CA 19-9 staining. The clinicopathological features of solitary true
      cyst of the pancreas in adults are briefly reviewed.

PMID- 9772069
TI  - Helicobacter pylori as a pathogenic factor in Menetrier's disease.
AB  - The cause of Menetrier's disease is unknown, although various autoimmune,
      allergic, and infective causes have been postulated. This case report describes a
      37-yr-old man with Menetrier's disease associated with protein-losing enteropathy
      and Helicobacter pylori infection. Clinical, endoscopic, histological, and
      biochemical resolution occurred after treatment of Helicobacter pylori infection.
      The improvement observed in this case supports an etiological role for H. pylori
      infection in Menetrier's disease.

PMID- 9772070
TI  - Fibrotic entrapment of the small bowel in congenital intestinal lymphangiectasia.
AB  - Congenital intestinal lymphangiectasia is a rare protein-losing enteropathy that
      is characterized by diarrhea and peripheral edema. This report presents a 37-yr
      old woman who had suffered from recurrent diarrhea and peripheral edema since her
      early childhood and who was admitted for severe attacks of abdominal pain. A
      diagnosis of intestinal lymphangiectasia was made endoscopically, histologically,
      and radiographically. Laparotomy revealed complete fibrotic entrapment of the
      small bowel, which caused partial mechanical bowel obstruction. Surgical
      decortication led to recovery. To the best of our knowledge, this is the first
      report on fibrotic entrapment of the small bowel in a patient with long lasting
      intestinal lymphangiectasia.

PMID- 9772071
TI  - Intrapancreatic ciliated enteric duplication cyst presenting with biliary
      obstruction.
AB  - A 46-yr-old man presenting with biliary obstruction from an intrapancreatic tumor
      underwent pancreaticoduodenectomy. The pathology report showed the tumor to be an
      enteric duplication cyst. Diagnostic imaging features and operative management
      are discussed.

PMID- 9772072
TI  - Successful steroid treatment of idiopathic thrombocytopenic purpura after
      orthotopic liver transplantation for primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver frequently
      associated with extrahepatic autoimmune phenomena. Specific antibodies against
      platelet glycoproteins may play an important role in the pathogenesis of
      thrombocytopenia associated with PBC. This is the first report of life
      threatening idiopathic thrombocytopenic purpura successfully treated with
      steroids in a 62-yr-old woman 2 yr after liver transplantation for PBC.

PMID- 9772073
TI  - Metastatic lung cancer presenting as cholecystitis.
AB  - We report the case of a 69-yr-old patient with inoperable cancer of the lung who
      later developed acute cholecystitis-related to metastasis to the gallbladder
      wall. Secondary malignancies of the gallbladder are discussed.

PMID- 9772074
TI  - Duodenal tuberculosis presenting as acute ulcer perforation.
AB  - Gastrointestinal tuberculosis (TB) is rare, but its incidence is increasing in
      industrialized countries because of the growing numbers of individuals at risk
      for TB. Herein, we report the exceptional case of a young, HIV-negative, African
      refugee who presented with acute perforation of an isolated duodenal tuberculous
      ulcer. Clinical patterns of duodenal TB are discussed. The difficulty of
      obtaining a diagnosis on the basis of clinical features, endoscopy, and imaging
      is emphasized, as well as the importance of obtaining a biopsy specimen and its
      limitations.

PMID- 9772075
TI  - Colonic cancer in a 34-yr-old woman: should it prompt microsatellite instability
      studies and mismatch repair gene testing?
AB  - It remains debatable whether young patients with colorectal tumors should undergo
      genetic testing with the aim of identifying new hereditary nonpolyposis
      colorectal cancer families. We describe a case of a young woman with colon cancer
      with no clinical criteria of hereditary nonpolyposis colorectal cancer, whose
      genetic analysis showed that the tumor displayed microsatellite instability, and
      in whom a truncated protein in hMSH2 gene was found, which was also present in
      two at-risk relatives.

PMID- 9772076
TI  - Granular cell tumor of the duodenum: a case report.
AB  - Granular cell tumor (GCT) in the duodenum is an extremely rare disease: only one
      case has been listed in a review, to date. We reported a 47-yr-old Japanese male
      case with GCT of the duodenum. Clinically, melena caused by bleeding from the
      tumor was the only symptom. The tumor cells showed abundant, granular
      eosinophilic cytoplasm. Although this tumor was clinically and histologically
      benign, highly developed tumor microvessels were demonstrated both
      angiographically and histologically, suggesting malignant potential of the tumor.

PMID- 9772077
TI  - Identification of patients with resectable pancreatic cancer: at what stage are
      we?
AB  - In a prospective evaluation of 58 consecutive patients referred for operation of
      a suspected pancreatic or peri-ampullary cancer, the accuracy of ultrafast
      magnetic resonance imaging (UMRI) in predicting the resectability of pancreatic
      tumors compared with alternative staging interventions was assessed. The staging
      methods included: 1) transcutaneous ultrasound (US) with color Doppler, 2) UMRI,
      including echoplanar sequences and breath-hold gadolinium-enhanced dual-phase
      three-dimensional magnetic resonance angiography (MRA), 3) rapid bolus dual-phase
      helical computed tomography (CT), 4) angiography of celiac and mesenteric
      arterial systems, including portal venous phase, and 5) endoscopic
      cholangiopancreatography (performed in jaundiced patients). Patients were
      evaluated for extrapancreatic tumor spread, presence of hepatic metastases, lymph
      node involvement, and vascular involvement--each a sign of unresectability. After
      an investigator blinded to the results of the other imaging studies assessed
      resectability, patients were then divided into three categories: 1) probably
      resectable, 2) probably unresectable, and 3) certainly inoperable. Final
      diagnosis was obtained by laparotomy (47 of 58 pts), or by histopathological
      examination of fine needle aspiration specimens in patients deemed inoperable.
      The 58 suspected tumors were localized to the pancreatic head in 35 (60%), body
      in 11 (19%), and tail in one (2%). Nine (16%) ampullary tumors and two (3%)
      distal common bile duct tumors made up the remainder. For those 52 patients for
      whom histology was obtained, 44 were malignant and eight benign. Accuracy for
      assessing extrapancreatic tumor extension was highest with UMRI (95.7%) followed
      by US (85.1%), and CT (74.4%). UMRI provided the best means for detecting liver
      metastases with an accuracy of 93.5% compared with 87.2% for each of US and CT.
      UMRI, US, and CT had a reduced capacity for detecting lymph node involvement
      (80.4%, 76.6%, and 69.2%, respectively). In assessing vascular invasion, UMRI had
      an accuracy of 89.1%, US 83.0%, CT 79.5%, and angiography 68.8%. The findings
      suggest that UMRI is equal to or superior to other staging methods with regards
      to sensitivity, specificity, and overall accuracy. Since UMRI has the potential
      to reduce patient time, money, and discomfort, this study concludes that this
      staging technique should replace alternative methods as it provides an "all-in
      one" diagnostic modality.

PMID- 9772078
TI  - Helicobacter colonization of the biliary tree: commensal, pathogen, or spurious
      finding?
AB  - The authors hypothesized that Helicobacter species may be present in the bile and
      gallbladder wall of patients with chronic cholecystitis who live in a region with
      a high prevalence of gallbladder cancer. They attempted to identify such species
      by obtaining both bile and resected gallbladder tissue from 46 patients who
      underwent cholecystectomy. Tissue specimens were stained with hematoxylin and
      eosin as well as other stains used specifically for the identification of
      Helicobacter species, and culture was attempted using specialized media on
      samples from tissue and bile. Unfortunately, the authors were unable to culture
      any Helicobacter species, and the yield from histopathology was also poor with
      silver stains identifying curved bacteria suggestive, but not diagnostic, of
      Helicobacter species in only two cases. Molecular techniques were more
      successful. DNA was extracted from both tissue and bile and amplified by
      polymerase chain reaction (PCR) using a specific primer. The amplicons they
      identified were then compared with known Helicobacter proteins using a Southern
      blot approach. PCR amplification was relatively successful with 9 of 23
      gallbladder samples and 13 of the 23 bile samples coming up positive for
      Helicobacter species using two specific primers. These specimens were also
      positive by Southern blot hybridization. The cloning and sequencing of the 16S
      ribosomal RNA amplicons in eight cases verified true Helicobacter origin with a
      phylogenetic analysis showing greater than 99.3% similarity. Five of the
      amplicons clustered with H. bilis, two with Flexispira rappini, and one with H.
      pullorum. The authors concluded that despite their being unable to identify
      organisms directly, the stringent PCR technique with amplicon sequencing
      confirmed that Helicobacter species could be identified within the bile and
      gallbladder tissue of patients with chronic cholecystitis in a region with high
      incidence of gallbladder cancer. They indicated that further studies are needed
      to ascertain whether similar species have a causative role in the development of
      gallbladder cancer.

PMID- 9772079
TI  - Bleeding ulcer: inject or clip?
AB  - The authors retrospectively compared endoscopic injection therapy with endoscopic
      hemoclipping by examining 113 patients over a 10-yr period between 1985 and 1995
      who had gastrointestinal bleeding and who received one or the other procedure.
      Endoscopic injection using ethanol alone, epinephrine plus ethanol, or
      aethoxysclelol plus ethanol was performed in 87 cases. Endoscopic hemoclipping
      was performed in 26 cases from 1993 to 1995. The permanent hemostasis rate of
      endoscopic injection was 84% and that of endoscopic hemoclipping was 100%.
      Complications associated with endoscopic injection included enlargement of the
      ulcer bed, bleeding caused by exposed vessels within the expanded ulcer and one
      case of perforation. No complications were noted among patients treated with
      endoscopic hemoclipping.

PMID- 9772080
TI  - Barbering, a probable risk factor for HCV transmission.

PMID- 9772081
TI  - Re: Gamagami et al. Fournier's gangrene with obstructing cancer.

PMID- 9772082
TI  - Baclofen therapy for intractable hiccups in pancreatic carcinoma.

PMID- 9772083
TI  - Fatal myocardial infarction in an elderly woman with severe ulcerative colitis:
      what is the role of steroids?

PMID- 9772084
TI  - Management of biliary ascariasis.

PMID- 9772085
TI  - Point prevalence of peptic ulcer and gastric histology in healthy Indians with
      Helicobacter pylori infection.

PMID- 9772086
TI  - Symptomatic eosinophilic esophagitis and esophageal candidiasis.

PMID- 9772087
TI  - Helicobacter pylori and gastric outlet obstruction.

PMID- 9772089
TI  - Marine biomolecules inhibit rat brain nitric oxide synthase activity.
AB  - A large number of substances of medical importance have been isolated from marine
      flora and fauna and their chemical structures were elucidated. Among the many
      compounds isolated in our laboratories only two compounds were identified as
      neurotoxins as they produced depolarizing effects in nerve fibers. The
      Xestospongin D and Araguspongin C, isolated and purified to 100% from sponge,
      Haliclona exigua were tested for their effects on rat brain nitric oxide synthase
      (NOS) activity in vitro. The results showed that NOS activity was significantly
      inhibited in a concentration and time dependent manner with an estimated IC50 of
      31.5 and 46.5 microM for Xestospongin D and Araguspongin C, respectively, and the
      maximum inhibition occurred within 3 min of incubation. To explore the mechanism
      of action of these compounds on NOS, we have conducted kinetic studies with L
      arginine, NADPH and Ca2+ in the presence of IC50 concentrations of these two
      compounds. The maximum velocity (Vmax) and enzyme constant (Km) were calculated
      using the Michaelis Menten equation. The results show that both compounds are
      competitive inhibitors of NOS with the substrate, L-arginine and uncompetitive
      with NADPH and free Ca2+. The NOS inhibition by these two compounds was similar
      to N omega-nitro-L-arginine methylester (L-NAME), a known inhibitor of NOS. These
      results suggest that the marine biomolecules Xestospongin D and Araguspongin C
      are in vitro modulators of neuronal NOS.

PMID- 9772088
TI  - Phencyclidine block of Ca2+ ATPase in rat heart sarcoplasmic reticulum.
AB  - Phencyclidine hydrochloride (PCP) also known as Angel Dust is a very potent
      psychotomimetic drug of abuse. Besides its central nervous system (CNS) effects
      PCP produces a number of adverse effects in a variety of tissues including the
      cardiovascular system. Since PCP is known to alter the cellular calcium
      homeostasis the present studies were initiated to determine the changes in
      cardiac Ca2+ ATPase activity in rats treated with PCP. For in vitro studies the
      cardiac sarcoplasmic reticulum (SR) fractions prepared from normal rats were
      incubated with 25, 50 and 100 microM PCP and the enzyme activities were
      estimated. Whereas, for in vivo studies the cardiac SR fractions prepared from
      rats treated with PCP (10 mg/kg body wt. single dose, intra-peritoneally (i.p.))
      and sacrificed at different time intervals were used. PCP reduced the Ca2+ ATPase
      activity significantly both in vitro and in vivo. A 50% inhibition of the enzyme
      activity was obtained with 100 microM PCP in vitro. A significant reduction of SR
      Ca2+ ATPase was also evident as early as 1 h after treatment of rats with PCP.
      The reduction of Ca2+ ATPase activity in SR was irreversible even at 12 h after
      treatment. The in vitro kinetic studies revealed that PCP was found to be a
      competitive inhibitor of Ca2+ ATPase with respect to the substrate, ATP, and non
      competitive with respect to Ca2+ activation. These results indicate that PCP
      alters the myocardial Ca2+ homeostasis by inhibiting the Ca2+ ATPase in cardiac
      SR in rats. Inhibition of SR Ca2+ ATPase may result in the impairment of
      contraction and relaxation coupling processes in the myocardium.

PMID- 9772090
TI  - Antimony trichloride induces DNA damage and apoptosis in mammalian cells.
AB  - Antimony compounds are widely used in various manufacturing and semiconducting
      industries. Previously, it has been shown that antimony trichloride (SbCl3)
      elevates sister chromatid exchange (SCE) rates in V79 cells after a 28-h
      incubation. However, only limited data on its genotoxic effects are available so
      far. The present results demonstrate that a 4-h exposure to > 50 microM SbCl3
      could induce micronuclei (MN) formation in cultured Chinese hamster ovary (CHO
      K1) cells, human bronchial epithelial (BES-6) cells and human fibroblasts (HF).
      The order of sensitivity to SbCl3 determined by Sulforhodamine B (SRB)-staining
      survival assay is HF > BES-6 cells > CHO-K1 cells, with LD50 values in these
      cells being approximately 40, 80 and 180 microM, respectively. Apoptosis and DNA
      fragmentation was not found in cells immediately following 4-h SbCl3 treatment.
      However, DNA fragmentation was detected in CHO-K1 cells after 4-h SbCl3 treatment
      and a 16 h or more post incubation in fresh medium by 1.5% agarose gel
      electrophoresis. The delayed apoptosis was also observed under microscopic
      examination in HF, BES-6 and CHO-K1 cells after similar treatment protocol. In
      addition, an increase in calcium accumulation appeared in CHO-K1 cells and HF
      immediately after a 4-h SbCl3 treatment, or after a 24-h post incubation in fresh
      medium. The present results provide important genotoxic and cytotoxic information
      characterizing the cellular changes induced by short-term SbCl3 exposure in
      rodent and human cells.

PMID- 9772091
TI  - Ethanol does not increase the hepatotoxicity of cocaine in primary rat hepatocyte
      culture.
AB  - Rat hepatocytes were utilized to investigate the role of cocaine metabolism and
      the contribution of ethylcocaine formation to cocaine-induced liver damage.
      Hepatocytes were prepared from rats pretreated with saline, phenobarbital or
      ethanol and exposed to cocaine, ethanol, or their combination. Hepatotoxicity was
      assessed by lactate dehydrogenase (LDH) leakage and was correlated with cocaine
      metabolism which was assessed quantitatively using HPLC. Only phenobarbital
      pretreatment produced increases in LDH leakage from cultures exposed to cocaine.
      This increase in LDH release occurred simultaneous to a decrease in
      benzoylecognine formation and a marked increase in norcocaine generation.
      Exposing cultures to ethanol alone did not result in LDH leakage from
      hepatocytes. Furthermore, including ethanol in cultures treated with cocaine did
      not enhance the LDH leakage produced by cocaine alone. This study confirms
      quantitatively that cocaine-induced hepatotoxicity is mediated through cocaine
      oxidative events and is enhanced by microsomal induction produced by
      phenobarbital. The finding that ethylcocaine formation was maximal in the ethanol
      pretreatment group where no toxicity was observed suggests that ethylcocaine is
      not the agent responsible for the hepatotoxicity observed in this study.

PMID- 9772092
TI  - Liver nuclear ethanol metabolizing systems (NEMS) producing acetaldehyde and 1
      hydroxyethyl free radicals.
AB  - Biotransformation of ethanol by liver nuclei was studied. The formation of
      acetaldehyde was determined by GC/FID. The 1-hydroxyethyl (1HEt) formation was
      established by spin trapping of the radical with N-t-butyl-alpha-phenylnitrone
      (PBN) followed by GC/MS. Liver nuclei, free of endoplasmic reticulum, cytosol or
      mitochondria, were able to biotransform ethanol to acetaldehyde in the presence
      of NADPH under air. Only 22% activity was observed in the absence of the
      cofactor. Twenty-six percent of the NADPH-dependent activity and 47% of the NADPH
      independent activity were observable under nitrogen. Aerobic biotransformation
      was inhibited by CO, SKF 525A, 4-methylpyrazole and by diethyldithiocarbamate.
      This suggests that CYP2E1 is involved in the process. However, the formation of
      acetaldehyde was able to proceed under a pure CO atmosphere. The lack of
      inhibitory effects of 2-mercapto-1-methylimidazol and thiobenzamide excludes the
      potential participation of the NADPH flavin monooxigenase system. The formation
      of hydroxyl radicals in the process is suggested by the partial inhibitory effect
      of 5 mM mannitol and 5 mM sodium benzoate and by the fact that the 1HEt was
      detected. The NADPH-dependent anaerobic ethanol biotransformation pathway was
      stimulated by FAD and inhibited to some extent by iron chelators. The relevance
      of a liver nuclear ethanol biotransformation, generating reactive metabolites,
      such as acetaldehyde and free radicals, nearby DNA, nuclear proteins and lipids
      is discussed.

PMID- 9772093
TI  - Localization of cytochrome P4501A1 and covalent binding of a mutagenic
      heterocyclic amine in blood vessel endothelia of rodents.
AB  - Immunohistochemistry was used to examine the cellular localization of cytochrome
      P4501A1 (CYP1A1) in various types of endothelial linings in muscle tissues of
      rats and mice treated with the Ah receptor agonist beta-naphthoflavone (BNF). In
      addition, light microscopic autoradiography was used to localize sites of
      metabolic activation of 3H-labeled Trp-P-1 (3-amino-1,4-dimethyl-5H-pyrido[4,3
      b]indole), a heterocyclic amine known to be metabolized by CYP1A1, in rodent
      tissue slices. The results showed a colocalization of CYP1A1 immunoreactivity and
      covalent binding of 3H-Trp-P-1 in endothelial linings of capillaries and veins of
      heart, skeletal muscle, and uterus in BNF-treated rodents, indicating the
      presence of catalytically active CYP1A1 at these sites. The immunohistochemical
      staining and covalent binding of 3H-Trp-P-1 in endothelia of arteries and
      arterioles was generally weak with the exception of uterine arterioles. In lymph
      nodes of BNF-treated rats, there was an intense CYP1A1 staining of high
      endothelial venules. The results suggest that endothelial linings of capillaries
      and veins in muscle tissues but also uterine arterioles and high endothelial
      venules in lymph nodes may be targets for CYP1A1-mediated metabolic products of
      endogenous and exogenous substances following exposure to CYP1A1 inducing agents.

PMID- 9772094
TI  - Plasma cadmium-metallothionein, a biological exposure index for cadmium-induced
      renal dysfunction, based on the mechanism of its action.
AB  - Thirteen rabbits were given subcutaneous cadmium (0.3 mg Cd/kg) daily. The plasma
      cadmium-metallothionein (CdMT) and the Cd-induced hepatic and renal functions
      were determined at 0, 5, 8, 11, 12, 13 and 14 weeks. Hepatic dysfunction, an
      elevated plasma CdMT and renal dysfunction were detected mostly between 12 and 14
      weeks. The hepatic dysfunction parameters were closely related with the plasma
      CdMT, which was then found to correlate with the renal dysfunction parameters.
      All the above findings suggest the following mechanism for the Cd-induced renal
      dysfunction: hepatic CdMT is released into the plasma upon the Cd-induced hepatic
      dysfunction, and then excess plasma CdMT, whose concentration is proportional to
      the CdMT in the renal proximal tubular lumen, induces renal dysfunction. The
      critical concentration of plasma CdMT to induce renal dysfunction was estimated
      as 80 microg Cd/l. The plasma CdMT is proposed therefore as a biological exposure
      index for the Cd-induced renal dysfunction, based on the mechanism of its action.

PMID- 9772095
TI  - Investigations of the pathways of toxicity of methyl iodide in the rat nasal
      cavity.
AB  - The monohalomethane methyl iodide (MeI) is a site specific toxin within the nasal
      cavity of the rat, selectively damaging the olfactory epithelium (OE) whilst
      respiratory epithelium (RE) is spared. The aim of this study was to investigate
      the rates and routes of metabolism of MeI within the nasal cavity, in order to
      understand the reasons for the observed site-selectivity. Cytosolic glutathione S
      transferases (GSTs) of both OE and RE catalysed the conjugation of MeI with
      glutathione (GSH), but rates were 4-fold higher in OE than RE. The product of
      this reaction was confirmed as S-methyl GSH. In both OE and liver the GST
      catalysing the conjugation of MeI was shown to belong to the theta class. No
      cytochrome P450-dependent oxidation of MeI to formaldehyde could be detected in
      incubations containing hepatic or olfactory microsomes. Intact nasal turbinates
      were incubated with [14C]-MeI, and a dose- and time-dependent covalent binding of
      MeI to olfactory protein was demonstrated. The rates of protein methylation were
      found to be similar in OE and RE. Thus the only parameter that correlates with
      the site-selectivity of the observed lesion is the rate of conjugation of MeI
      with GSH. Whether toxicity is due to production of a reactive metabolite or GSH
      depletion per se, remains to be elucidated.

PMID- 9772096
TI  - Adaptation to oxidative stress: effects of vinclozolin and iprodione on the HepG2
      cell line.
AB  - It is well known that the dicarboximide fungicides, vinclozolin and iprodione,
      induce lipid peroxidation by means of oxygen activation in fungi, but their
      action on mammalian cells is not yet clear. We therefore investigated the effect
      of 1- and 24-h treatments with vinclozolin at concentrations of 25, 50, 100
      microg/ml and iprodione at concentration of 62.5, 125, 250 microg/ml on
      malonaldehyde and free radical production and on reduced glutathione levels in
      the human HepG2 hepatoma cell line. The concentrations were chosen on the basis
      of neutral red cytotoxicity assays. One-hour treatment with the different
      concentrations of either vinclozolin or iprodione increased both malonaldehyde
      and free radical content, and decreased reduced glutathione levels, whereas 24-h
      treatment decreased malonaldehyde content and free radical production, and
      increased reduced glutathione concentration. These results suggest that the
      mammalian cells respond to the initial oxidative damage caused by the two
      dicarboximide fungicides by means of a characteristic adaptative phenomenon
      within 24 h. This hypothesis is supported by the antagonized effects caused by
      treatment with the two dicarboximide fungicides and buthionine sulfoximine 0.5
      mM, a specific and irreversible inhibitor of reduced glutathione synthesis. The
      data confirm that the two dicarboximide fungicides maintain their specific action
      in mammalian cells, although this action is masked by adaptation.

PMID- 9772097
TI  - Selective induction of cell-associated interleukin-1alpha in murine keratinocytes
      by chemical allergens.
AB  - Cytokines may be useful tools to discriminate between irritant and allergic
      contact dermatitis. In the mouse only, it has been demonstrated by other, that
      contact sensitizers up-regulated keratinocytes-derived interleukin-1alpha (IL-1),
      macrophage inflammatory protein-2 and interferon induced protein 10 mRNAs. The
      purpose of this study was to investigate the possibility to use in vitro IL-1
      production by a murine keratinocyte cell line for preliminary screening of
      chemicals for their irritant and/or allergic potential. We investigated the
      effects of five relevant skin allergens (dinitrochlorobenzene, oxazolone, nickel
      sulfate, penicillin G and eugenol), two skin irritants (benzalkonium chloride,
      and methylsalicilate) and two compounds with no sensitizing activity (glycerol
      and ethanol) on IL-1 production in HEL30 cells. Twenty four hours following
      treatment, both IL-1 release in conditioned media and cell-associated IL-1 were
      measured by a specific sandwich ELISA. Under our experimental conditions, only
      contact sensitizers were able to increase in a dose dependent fashion cell
      associated IL-1, confirming the in vivo findings. Both skin irritants and
      allergens induced the release of IL-1, because of the irritative properties of
      both chemicals, while ethanol and glycerol failed to induce changes in IL-1
      production, confirming the specificity of the proposed test. Taken together,
      these data indicate that it may be realistic to consider potential skin allergens
      those chemicals which are able to increase cell-associated IL-1, to consider skin
      irritants those chemicals which induce only IL-1 release, and to exclude as
      potential allergens or irritants those chemicals which fail to induce changes in
      IL-1 production.

PMID- 9772098
TI  - Effects of prolonged exposure to morphine and methadone on in vivo parameters of
      immune function in rats.
AB  - In rats, two 6-week repeated dose oral toxicity studies were performed with
      morphine (250 and 500 mg/kg food) and methadone (200 and 400 mg/kg food),
      respectively. Alterations in immune function were studied by assessing primary
      and secondary immune responses to sheep red blood cells. In addition, the ability
      to resist challenge with infectious agents was measured in host resistance models
      employing the parasite Trichinella spiralis and the bacterium Listeria
      monocytogenes. The primary and secondary antibody responses to sheep red blood
      cells were not affected by treatment with either morphine or methadone. The
      clearance of L. monocytogenes bacteria in the spleen was not affected either.
      Prolonged treatment with morphine, however, resulted in a decrease in host
      resistance to T. spiralis infection, as indicated by a 1.5-fold increase in
      numbers of muscle larvae counted in the carcass, but did not affect the T.
      spiralis-specific IgM, IgG and IgE antibody responses. In contrast to morphine,
      the methadone-treated animals did not show a significant change in host
      resistance to T. spiralis. Total serum IgG levels, however, were increased in
      high-dose methadone-treated animals. Apparently, prolonged administration of
      morphine to rats resulted in immune suppression, mediating a slight, though
      biologically relevant, exacerbation of the T. spiralis infection, whereas
      methadone did not.

PMID- 9772099
TI  - Differential induction of apoptosis in activated and resting T cells by 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) and its repercussion on T cell responsiveness.
AB  - TCDD is well known for its immunotoxic effects on T cells, although the exact
      mechanism of toxicity remains unknown. In the current study, we investigated the
      effect of TCDD administration on resting and activated T cells within the same
      animal. To this end, C57BL/6 mice were injected intraperitoneally with either
      TCDD (50 microg/kg body weight) or the vehicle and were injected with anti-CD3
      mAbs into the rear footpads to polyclonally activate T cells in the popliteal
      lymph nodes (LN). Axillary LN cells harvested from the same groups of mice served
      as a source of resting T cells. When the LN cells were tested for their
      proliferative responsiveness to stimulation with anti-CD3 mAbs in vitro, the
      activated popliteal LN, but not the resting axillary LN cells from TCDD-treated
      mice exhibited a significant decrease in responsiveness when compared to the
      vehicle controls. Inasmuch as TCDD has been shown to induce apoptosis in
      thymocytes, we addressed whether TCDD triggered apoptosis in LN cells, using the
      terminal deoxynucleotidyl transferase (TdT)-mediated FITC-dUTP nick end labeling
      (TUNEL) method. The axillary and popliteal LN cells from TCDD-treated mice failed
      to exhibit significant levels of apoptosis when freshly harvested. However, upon
      in vitro culture for 24 h with either tissue culture medium alone or with anti
      CD3 mAbs, activated popliteal LN cells from TCDD-treated mice showed a
      significant increase in apoptosis when compared to similar cells from vehicle
      treated mice. In contrast, resting axillary LN cells from TCDD-treated mice,
      similarly cultured in vitro, exhibited decreased levels of apoptosis when
      compared to the controls. Using a double-staining technique, the activated
      popliteal LN cells undergoing increased apoptosis in TCDD-treated animals were
      confirmed to be CD3+ T cells. Together, these data demonstrate that TCDD exerts
      differential effects on activated and resting T cells, even within the same
      animal, by inhibiting the proliferative responsiveness of activated, but not
      resting, T cells. Furthermore, this effect may be mediated by the ability of TCDD
      to induce increased apoptosis in activated, but not resting, T cells.

PMID- 9772100
TI  - Airborne house dust elicits a local lymph node reaction and has an adjuvant
      effect on specific IgE production in the mouse.
AB  - Indoor suspended particulate matter (SPM) consists of many different types of
      particles, the vast majority of which are less than 2.5 microm in diameter. An
      important question is how these particles, being inhalable, contribute to asthma
      and respiratory symptoms. One possibility is that these particles have an
      adjuvant effect on the immune response and increase the IgE production, or cause
      a non-specific irritation in the airways, contributing to bronchial hyper
      responsiveness. In this study, the adjuvant activity of indoor SPM on the
      response to the model allergen ovalbumin (OA) in BALB/c mice was investigated,
      using the popliteal lymph node (PLN) assay. The adjuvant activity on the local
      lymph node response was determined by measuring the PLN weight, cell numbers and
      cell proliferation, and the adjuvant activity on the IgE production by measuring
      the levels of serum IgE specific to OA. SPM was found to give a significant PLN
      response, both when injected alone and together with OA. SPM was also found to
      enhance the production of specific IgE to OA when injected together with OA,
      after reinjection with OA, compared with immunisation with OA alone.

PMID- 9772101
TI  - Association of spatial distribution of childhood respiratory morbidity with
      environmental dust pollution.
AB  - The objective of this study was to investigate the spatial distribution of
      respiratory morbidity and asthma in children in relation to high levels of
      airborne dust pollution. A cross-sectional survey of 2035 children (aged 5-11 yr)
      by parent-completed questionnaire, with concurrent monitoring of dust deposition
      rates in the vicinity of children's homes, was performed in 15 primary schools (5
      in each of 3 areas of Merseyside). The main outcome measures were (1) doctor
      diagnosed asthma, (2) parent-reported respiratory symptoms of recent excess
      cough, wheeze, and breathlessness, and (3) school absenteeism due to respiratory
      ill health. Proximity to the source of dust pollution was associated with
      increased prevalence of excess cough, breathlessness, school absence due to
      respiratory ill health, and doctor-diagnosed asthma, after adjusting for a range
      of socioeconomic, environmental, and other confounding factors. The adjusted odds
      for excess cough and breathlessness for children living within 2 km of the source
      (dock area) are estimated to be almost twice those for children living more than
      2 km away: excess cough 1.9 (95% CI 1.4-2.6); breathlessness 1.9 (1.3-2.7);
      school absence 1.5 (1.2-1.9); and doctor-diagnosed asthma 1.5 (1.1-2.0). Excess
      cough was significantly associated with the mean annual dust deposition recorded
      in the vicinity of the child's home. The adjusted odds ratio for excess cough
      corresponding to an increase in mean annual dust deposition of 50 mg/m2/d was 3.1
      (95% CI 1.1-8.2). These results suggest that airborne dust was associated with
      respiratory morbidity in these children, which could relate to the high
      prevalence of childhood doctor-diagnosed asthma in this community.

PMID- 9772102
TI  - Cardiovascular disease hospitalization and ambient levels of carbon monoxide.
AB  - Recent research suggests that some cases of cardiovascular mortality may be
      related to carbon monoxide (CO) air pollution. Clinically based studies indicate
      the adverse effects of CO on the cardiopulmonary system. However, little
      attention has been paid to the question of hospital admissions for cardiovascular
      illness caused by ambient CO levels. The present study assesses the association
      between hospital admissions for cardiovascular system illnesses and the ambient
      levels of CO in the Reno-Sparks, NV, area over a 6-yr period (1989-1994). Daily
      admissions to all three hospitals in the region and daily ambient concentrations
      of CO, monitored at five sites, were included. There were 32,705 total
      cardiovascular (CV) admissions, including 13,108 with the diagnosis of ischemic
      heart disease (IHD) during the study period. The average daily 1-h maximum level
      of CO was 3.09 ppm. After adjusting for day-of-the-week and seasonal effects and
      controlling for the effects of autocorrelation errors, both weighted least
      squares (WLS) and autoregressive integrated moving average (ARIMA) methods showed
      consistently positive relationships between the ambient CO level and different
      groups of cardiovascular admissions, although the male gender and age older than
      60 groups tended to be most affected. Data suggest a positive correlation between
      ambient CO levels and hospital admissions for CV diseases.

PMID- 9772103
TI  - Tributyltin modulates 3,3',4,4',5-pentachlorobiphenyl (PCB-126)-induced hepatic
      CYP1A activity in channel catfish, Ictalurus punctatus.
AB  - Many harbor estuaries and their tributaries are contaminated with halogenated
      aromatic hydrocarbons (HAHs) and polycyclic aromatic hydrocarbons (PAHs). Planar
      congeners of these two classes initiate their toxic effects, including
      reproductive, developmental, and immunological dysfunction, primarily through the
      cytosolic arylhydrocabon receptor (Ahr). However, only rarely are aquatic
      environments contaminated with Ahr-binding contaminants alone. Instead, most are
      impacted by a variety of pollutants in mixture. Tributyltin (TBT), a common
      antifouling biocide, is also found in many harbor estuaries and their
      tributaries. Several reports indicate that TBT inhibits the cytochrome P-4501A
      system of fish, at least in vitro, and our recent studies with rodents indicate
      that TBT potentiates PCB-induced CYP1A. However, the effects of TBT on xenobiotic
      induced CYP1A activity in aquatic organisms has been virtually unexplored. To
      this end, channel catfish, Ictalurus punctatus, were exposed to 3,3'4,4',5
      pentachlorobiphenyl (PCB-126, PeCB), TBT, or both in combination, with corn oil
      (CO) serving as the carrier control. Immunoreactive CYP1A protein and
      ethoxyresorufin O-deethylase (EROD) activity were measured after (1) a single
      dose of 0.01, 0. 1, or 1 mg/kg of each or both in combination, and (2) 6
      injections of 0.017, 1.7, or 17 microg/kg of each (or in combination) given every
      3 d over a 16-d period to yield a cumulative dose of 0.01, 0.1, or 1 mg/kg. As
      expected, PeCB alone, but not TBT, greatly induced these two CYP1A parameters.
      Low and middle doses of TBT (0.01 and 0.1 mg/kg), but not the high dose,
      potentiated PeCB-induced activity at these same doses. This effect of TBT was
      even more pronounced in the repeated exposure study. Furthermore, EROD activity
      did not always reflect CYP1A protein induction; enzyme activity was inhibited by
      TBT at doses that potentiated protein induction (0.01 and 0.1 mg/kg). In summary,
      TBT potentiates PeCB-induced CYP1A in channel catfish at doses that may be
      considered environmentally relevant.

PMID- 9772104
TI  - Effect of Ni2+ on the testosterone production of mouse primary Leydig cell
      culture.
AB  - This study evaluated the effects of Ni2 on testosterone (T) production of mouse
      Leydig cells in vitro following an in vivo or in vitro exposure. CFLP mice were
      subjected to repeated exposure (4 treatments, subcutaneously, every 3 d) to 10,
      20 or 40 mg/kg body weight of NiSO4 or 1.0 ml of 0.9% NaCl solution. Depressed
      human chorionic gonadotropin (hCG)-stimulated T response was seen over a 48-h
      culture of testicular interstitial cells obtained from the animals exposed to 20
      mg/kg or higher dose of NiSO4, while the basal T production remained unaltered.
      There were no Ni2+-related changes in the body weights or in the weights of
      testes, epididymides, adrenals, and kidneys. No histopathological alteration was
      found in the examined organs of NiSO4-treated groups except the dose-dependent
      tubular lesions in kidney as a result of a specific rather than a general
      cytotoxic action. To assess the direct effect of Ni2+ on Leydig-cell T
      production, testicular interstitial cells were cultured with Ni2+ (62.5 to 1000
      microM) for 48 h in the presence or absence of maximally stimulating
      concentration of hCG. Dose-dependent depression in hCG-stimulated T production
      was seen at 125 microM or higher dose of Ni2+, while basal T production was
      unaffected. In order to evaluate the time dependency of this effect the cells
      were cultured for various times in the presence or absence of 250 and 1000 microM
      Ni2+. Decreased hCG-stimulated T production was found in the cultures maintained
      at least for 4 h in the presence of 1000 microM Ni2+, whereas at 250 microM at
      least 16 h was required to elicit the depression. Cell viability was assessed by
      a metabolic activity (MTT) assay. The viability of cells was unaltered by 250
      microM Ni2+, and only a slight decrease was found even at the end of the 48-h
      culture period in the presence of 1000 microM Ni2+. Our results show a dose
      related depression in stimulated T production of mouse Leydig cells in culture
      following either in vivo or in vitro Ni2+ treatment at a dose that does not
      induce any general toxic or significant cytotoxic action. The data of the time
      course study indicate that the effect of Ni2+ on Leydig-cell T production is both
      time and concentration dependent, and not due to cytotoxicity.

PMID- 9772105
TI  - 2-Aminophenol and 4-aminophenol toxicity in renal slices from Sprague-Dawley and
      Fischer 344 rats.
AB  - This study examined differences in toxicity between 2- and 4-aminophenol using a
      renal cortical slice model. Renal cortical slice toxicity for 2- and 4
      aminophenol was also monitored in tissue from Sprague-Dawley and Fischer 344
      (F344) rats in order to determine potential strain differences for aminophenol
      toxicity. Renal cortical slices from Sprague-Dawley and F344 rats (age 50-65 d)
      were isolated and incubated for 15-120 min with 0-1 mM 2- or 4-aminophenol at 37
      degrees C under an oxygen atmosphere. Elevations in lactate dehydrogenase (LDH)
      leakage from renal cortical slices occurred at lower concentrations of 4
      aminophenol than of 2-aminophenol from both strains of rats. Total glutathione
      levels were more markedly decreased by 4-aminophenol than by 2-aminophenol in
      renal slices from both strains. LDH release was elevated by 1 mM 2-aminophenol in
      renal slices from F344 rats, but values were comparable between control and
      treated in the renal slices from Sprague-Dawley rats. 4-Aminophenol was slightly
      more toxic to renal slices from F344 than from Sprague-Dawley rats. LDH release
      was increased, relative to controls, by 0.1 mM in the F344 rats group compared to
      0.25 mM in the Sprague-Dawley group. Strain differences were not apparent when
      comparisons were made of total glutathione levels or rate-limiting substrates of
      gluconeogenesis. These results indicated that strain differences in toxicity were
      detected between Sprague-Dawley and F344 rat strains. Based on LDH release, renal
      cortical slices obtained from age-matched F344 rats were slightly more
      susceptible than Sprague-Dawley rats to toxicity by 2- and 4-aminophenol.

PMID- 9772106
TI  - Oculomotor sequence learning: a positron emission tomography study.
AB  - The purpose of this study was to identify the brain regions activated in relation
      to oculomotor sequence learning. Nine healthy subjects participated in the study,
      which consisted of three positron emission tomography scans. In the initial
      learning task, subjects were instructed to track a sequence of seven successive
      positions of visual targets and to memorize the order of the targets as well as
      their spatial locations. In the saccade task, subjects were instructed to track
      visual targets presented at random locations. In the control task, subjects were
      instructed to gaze at a fixation point. Fields showing significant regional
      cerebral blood flow change were determined from task-minus-control subtraction
      images. We determined that fields in the pre-supplementary motor area (pre-SMA),
      the intraparietal cortex, and the prefrontal cortex were activated not only in
      the learning-minus-control images but also in the learning-minus-saccade images.
      Although prefrontal and parietal activations were bilateral, pre-SMA activation
      was confined to the left hemisphere. The results indicate that these fields
      function as a part of the neural network involved in the learning of sequential
      saccadic eye movements.

PMID- 9772107
TI  - Human brain activity related to speed discrimination tasks.
AB  - The regional cerebral blood-flow (rCBF) pattern of the human brain was measured
      using positron emission tomography (PET) while subjects viewed, detected, judged
      the speed of a moving random dot pattern (RDP) or compared speeds of successive
      RDPs. In all four conditions, retinal input was identical. Two additional
      conditions, continuous presentation of a moving and a stationary RDP, were
      included to identify human MT/V5 (hMT/V5). Both speed discrimination tasks
      involved the right cuneus and right lingual gyrus and to a lesser degree the left
      lingual gyrus and a more anterior lingual region in the right hemisphere. There
      was, however, little or no differential activity over hMT/V5 during either speed
      discrimination. Direct comparison of the two speed discrimination tasks revealed
      higher activity in the right middle fusiform gyrus, a result reminiscent of that
      obtained in earlier studies using orientation and direction as the attribute to
      be discriminated. These results confirm that processing in the human visual
      cortex is task dependent and underscore the role of the middle fusiform gyrus in
      temporal comparison of simple attributes.

PMID- 9772108
TI  - Functional modification of agonist-antagonist electromyographic activity for
      rapid movement inhibition.
AB  - Subjects made a fast elbow extension movement to designated target in response to
      a go signal. In 45% of trials a stop signal was presented after the go signal, to
      which subjects were asked to stop the movement as rapidly as possible. The
      interstimulus interval (ISI), or time interval between the go and stop signals,
      was randomly varied between 0 and 200 ms. Electromyographic (EMG) activity was
      recorded from biceps brachii and triceps brachii. Subjects could sometimes
      completely inhibit initiation of the movements when the ISI was 0 ms, but could
      rarely do so when the ISI exceeded 100 ms. For responses that were initiated but
      stopped on the way, the amplitude of the movement decreased linearly as the time
      interval (=modification time) from the stop signal to EMG onset increased. The
      peak velocity increased linearly as the movement amplitude increased. This
      tendency was similar to those previously reported in step-tracking movements with
      various amplitudes. In spite of the similarity in the kinematics of the movement,
      the EMG pattern was different from that of step-tracking movement. While the
      initial agonist burst (AG1) decreased linearly after the modification time
      exceeded 100 ms, the antagonist burst (ANT) increased compared with the go trial
      for the modification time from 0 to 200 ms and decreased after the modification
      time exceeded 300 ms. This change of activation is analogous to functional
      modification of middle-latency reflex EMG response to load, or cutaneous
      perturbation. In conclusion, it is suggested that adaptive mechanisms, which
      would functionally modify the reflex responses, are also continuously working
      during voluntary movements in response to sudden changes in environmental
      information.

PMID- 9772109
TI  - Adaptive changes in responses to repeated locomotor perturbations in cerebellar
      patients.
AB  - This study examined the responses of cerebellar patients and a group of age- and
      sex-matched control subjects to repeated changes in treadmill speed in order to
      test whether cerebellar patients can adapt their gait to this type of
      perturbation and, if so, whether their responses are comparable to those of
      controls. While the subject walked on the treadmill, a perturbation consisting of
      a sudden slowing of the treadmill followed by a sudden increase back to the
      original speed was applied repeatedly at a specific time during the step cycle.
      Both the control subjects and cerebellar patients were able to compensate for the
      perturbations by minimizing their postural sway and changing step length.
      However, the nature of the compensatory changes in step length differed between
      these subject groups. Control subjects compensated for the perturbation by
      consistently using the same leg to initiate the response to the perturbation and
      by adapting a pattern of stepping such that the EMG characterizing the response
      occurred in a manner that was entrained to the timing of the normal locomotor
      cycle. In contrast, the patients, although undergoing modifications in step
      length, employed a much less consistent motor pattern from trial to trial than
      that of the normal subjects. An inconsistent pattern among their responses was
      apparent in both the analysis of stepping and in the EMG activity of the
      gastrocnemius and anterior tibial muscles. These results suggest that, although
      the cerebellar patients can adapt their behavior in response to locomotor
      perturbations, they do not establish a motor pattern comparable to that employed
      by normal subjects.

PMID- 9772110
TI  - Recordings of polymodal single c-fiber nociceptive afferents following mechanical
      and argon-laser heat stimulation of human skin.
AB  - Recordings were made in the peroneal nerve of healthy volunteer subjects from C
      mechano-heat (CMH) nociceptors (n=25) with their receptive fields in the skin on
      the dorsum of the foot. The investigation focused on afferent single C-fiber
      activity induced by short (200 ms) high-intensity argon-laser light pulses
      projected to localized spots of the skin. Cutaneous heat stimulation with the
      argon laser, 2-3 times the activation threshold, induced inter-burst spike
      frequencies in the nerve, reaching 50 Hz, while mechanical stimulation 10-20
      times threshold only evoked frequencies reaching 10 Hz. The decrease in
      conduction velocity of action potentials in the C-fiber afferents following
      mechanical and heat stimulation was closely related to the degree of activation.
      Following a laser pulse of 200 ms, a spike pattern with highly reproducible inter
      spike intervals was evoked with a fast saturation. On the contrary, a high
      variability in the number of action potentials evoked by both heat and mechanical
      stimuli was found, depending on the location of stimuli within the receptive
      field. A relation between the conduction velocity and the peak firing within the
      spike train following laser stimulation was detected. Heat and mechanical
      stimulation activated single C-fibers in matching spots within the same skin
      areas, in line with the assumption that the two modalities in the CMH-fibers
      share matching morphological cutaneous substrates. No correlation was found in
      thresholds or excitability to mechanical and heat stimulation, respectively. This
      suggests that subsets of receptors exist within nerve endings of the cutaneous
      receptive fields, with the ability to generate action potentials independent of
      heat and mechanical stimuli. Unexpectedly, no signs of sensitization or other
      inflammatory responses were observed after repeated laser pulses; on the
      contrary, a rapidly developing fatigue was observed when single spots were
      repeatedly stimulated. However, no fatigue was observed if neighboring spots were
      stimulated, indicating a localized generator of the fatigue. In each subject, a
      good correlation was observed between the reported pain sensation and the
      activity evoked in the afferent C-fibers by the laser. However, the magnitude of
      the reported pain sensation to comparable degrees of C-fiber activation showed a
      high variability between different subjects. A fairly good subjective estimate of
      the afferent-fiber activation was observed when skin spots from 3- down to 1-mm
      diameter were stimulated. In a few individuals, no painful sensation was reported
      when the stimulated spots were reduced to 1-mm diameter, despite the occurrence
      of multiple spikes in single C-fiber afferents, amplifying the importance of
      spatial summation in the perception of pain.

PMID- 9772111
TI  - Recordings of human polymodal single C-fiber afferents following mechanical and
      argon-laser heat stimulation of inflamed skin.
AB  - Activity in single C-fiber afferents, whose cutaneous receptive fields were on
      the dorsal side of the foot (n=10), were recorded in the peroneal nerve of
      healthy voluntary subjects. Characterization of the fibers with respect to
      thresholds and field areas were made before and after cutaneous inflammation,
      which was induced with mustard oil. To test the nociceptive heat modality, a high
      intensity argon laser was used and single 200-ms light pulses were focused onto
      the skin. The mechanical properties were tested with von Frey-type filaments. In
      the uninflamed skin, heat and mechanical stimulation activated single C-fibers in
      matching skin areas. The areas were all within the receptive field borders
      defined by electrical cutaneous stimulation. The mustard-oil-induced cutaneous
      inflammation was subjectively reported by the subjects as being moderately
      painful. In six of the units, a spontaneous activity was induced in the sample of
      ten previously non-active units. Before the inflammation, the 200-ms argon-laser
      pulse evoked a highly reproducible pattern of spike-trains. Following
      inflammation, this pattern was reproducible, but appeared with a significantly
      reduced activation rate despite the same energy being delivered to the skin both
      before and after the inflammation. A reduction in slope of the stimulus-response
      relationship was also observed after inflammation. Following inflammation,
      changes occurred with expansion both of the mechanical- and heat-receptive
      fields. The expansion was delineated by the areas defined by electrical
      stimulation. Following inflammation, the threshold to heat was decreased, but
      that to mechanical stimuli was not. No relation was detected between the
      threshold change and the degree of receptive-field expansion. The subjective pain
      reported changed following inflammation with an increase in the perceived pain in
      relation to the recorded action potentials, which emphasizes the importance of
      either an increase in sensitivity in the central nervous system or an increase in
      peripheral spatial summation after inflammation.

PMID- 9772112
TI  - Scalp distribution components of brain activity evoked by visual motion stimuli.
AB  - We analyzed the scalp distribution of electrical brain activity elicited by
      visual motion stimuli in 14 healthy adults. Stimuli were square-wave gratings of
      high or low contrast moving with a velocity of 4.9 deg/s on a computer monitor.
      Adaptation to motion was varied by changing the so-called duty cycle of stimulus
      presentation (i.e., the relation of motion to total presentation time) in order
      to enhance motion-related activity. Data obtained with motion stimuli were
      compared with checkerboard pattern reversal evoked activity. Spatial principal
      components analysis revealed four latent topographical components that accounted
      for 92.05% of the variance. Two components showed occipital extreme values
      surrounded by steep potential gradients while another two components displayed
      lateralized activity. Analysis of the contribution of these spatial components to
      the observed potential fields revealed significant differences between activity
      evoked by pattern reversal and that evoked by motion. The topographical patterns
      of cortical activation changed rapidly within 240 ms after motion onset. Our
      results confirm the sequential and parallel activation of different neuronal
      generators selectively sensitive to physical stimulus parameters of motion
      stimuli. The converging evidence of specialized quality-specific streams of
      sensory processing stemming from single-unit recordings in monkeys and imaging
      methods is supplemented by our electrophysiological results reflecting the
      activation of different brain areas.

PMID- 9772113
TI  - Motor redundancy during maximal voluntary contraction in four-finger tasks.
AB  - The goal of the study was to investigate force-sharing patterns in multi-finger
      tasks. Maximal normal force (MNF) as well as the force-time curves produced by
      individual fingers were measured in 10 young male subjects in three tasks: (1)
      holding an instrumented handle in a pad opposition with the thumb at seven
      different locations, from opposing the index finger (L0) to opposing the little
      finger (L6); (2) holding the handle in a pad opposition with the thumb at an
      individually selected comfortable location; and (3) pressing with the four
      fingers against the same handle fixed to the external support. We found that: (1)
      The moment due to the normal finger forces changed systematically when the thumb
      position varied from L0 to L5/ L6, and it was equal to zero at a certain middle
      position of the thumb, the neutral position. At this position, the shear force
      produced by the fingers was zero. (2) The total MNF changed in an ascending
      descending manner when the thumb position varied from L0 to L5/L6. The highest
      value of the maximal total normal force was produced at a position of the thumb
      that was preferred as the most comfortable position in the grip task. (3) In the
      press task, the neutral line - the line with respect to which the moment
      generated by the four fingers equals zero - was at the same location as the
      preferred thumb position in the grip tasks. (4) Larger total normal force
      corresponded to smaller total shear forces. (5) In grip tasks, with the thumb in
      a comfortable position, the force-force relationships among fingers were
      approximately linear. Hence, in these thumb positions, the force-sharing pattern
      was established at the beginning of the trial. At the extreme positions of the
      thumb, irregular patterns of the force-force relationships were observed. (6) In
      trials with different thumb locations, a significant correlation was found
      between the maximal force produced by the index and small fingers. (7) Peak force
      exerted by individual fingers in the multi-finger tasks was much smaller than the
      maximal force displayed by the same fingers in the single-finger tasks. The peak
      force depended on the thumb position and varied from 11.3% to 65.2% of the
      maximal force exerted by the same finger in the single-finger task. With the
      thumb in the comfortable position, the relative peak force for all fingers was
      approximately at the same level, 50-55%. The data are in agreement with the
      hypothesis that the total force is shared among individual fingers, minimizing
      the moment with respect to the functional hand axis.

PMID- 9772114
TI  - Facilitation of muscle evoked responses after repetitive cortical stimulation in
      man.
AB  - The technique of repetitive transcranial magnetic stimulation (rTMS) allows
      cortical motor areas to be activated by trains of magnetic stimuli at different
      frequencies and intensities. In this paper, we studied long-term
      neurophysiological effects of rTMS delivered to the motor cortex at 5 Hz with an
      intensity of 120% of motor threshold. Each stimulus of the train produced muscle
      evoked potentials (MEPs) in hand and forearm muscles, which gradually increased
      in size from the first to the last shock. After the end of the train, the
      response to a single-test stimulus remained enhanced for 600-900 ms. In contrast,
      the train had no effect on the size of the MEPs evoked by transcranial electrical
      stimulation, while it suppressed H-reflexes in forearm muscles for 900 ms. We
      conclude that rTMS of these parameters increases the excitability of the motor
      cortex and that this effect outlasts the train for almost 1 s. At the spinal
      level, rTMS may increase presynaptic inhibition of Ia afferent fibers responsible
      for the H-reflex.

PMID- 9772115
TI  - Movement detection at the distal joint of the human thumb and fingers.
AB  - To determine whether proprioceptive acuity is the same at all digits,
      particularly when postured as in a 'grasp', we imposed 10 degrees movements at
      the distal joint of the thumb, index and ring finger, at three velocities; 1.25
      degrees/s, 2.5 degrees/s and 5 degrees/s. The test joint was initially flexed by
      25 degrees and the joints proximal to the test joint were maintained in a
      standard posture for each study. When in a grasp posture that disengaged the
      extensor muscles at the distal joint of the finger, movement detection at the
      thumb was superior to that at the fingers for all velocities. However, when the
      fingers were positioned so that all proprioceptive inputs were able to contribute
      (i.e. cutaneous, joint and both flexor and extensor muscle afferents),
      proprioceptive acuity was similar for the three digits. Loss of local cutaneous
      (and joint) inputs by digital anaesthesia significantly impaired performance at
      all digits, suggesting a critical role for cutaneous input in normal
      proprioceptive sensibility at all distal joints of the digits. Anaesthesia of the
      extensor muscle afferents innervating the thumb did not affect its proprioceptive
      acuity. Thus, for the thumb, the extensor muscle afferents do not provide
      critical information. The greater change in muscle fascicle length for the
      thumb's long flexor muscle (3% per 10 degrees) compared with that in the finger
      flexor muscles (e.g. 0.1% per 10 degrees) could contribute to the thumb's
      performance. There appears to be less redundancy of muscle and non-muscle signals
      for the fingers than for the thumb, because a reduction in either cutaneous or
      muscle input significantly impaired acuity at the fingers. Overall, when the hand
      is in a grasping posture, irrespective of the contribution of local cutaneous
      inputs, the long flexor acting on the thumb may contribute more to its
      proprioceptive acuity than the long finger flexors contribute to acuity at the
      fingers.

PMID- 9772116
TI  - Updating visual space during passive and voluntary head-in-space movements.
AB  - The accuracy of our spatially oriented behaviors largely depends on the precision
      of monitoring the change in body position with respect to space during self
      motion. We investigated observers' capacity to determine, before and after head
      rotations about the yaw axis, the position of a memorized earth-fixed visual
      target positioned 21 degrees laterally. The subjects (n=6) showed small errors
      (mean=-0.6 degrees) and little variability (mean=0.9 degrees) in determining the
      position of an extinguished visual-target position when the head (and gaze)
      remained in a straight-ahead position. This accuracy was preserved when subjects
      voluntary rotated the head by various magnitudes in the direction of the
      memorized visual target (head rotations ranged between 5 degrees and 60 degrees).
      However, when the chair on which the subjects were seated was unexpectedly
      rotated about the yaw axis in the direction of the target (chair rotations ranged
      between 6 degrees and 36 degrees ) during the head-on-trunk rotations, the
      performance was markedly decreased, both in terms of spatial precision (mean
      error=5.6 degrees ) and variability (mean=5.7 degrees). A control experiment
      showed that the prior knowledge of chair rotation occurrence had no effect on the
      perceived target position after head-trunk movements. Updating an earth-fixed
      target position during head-on-trunk rotations could be achieved through both
      cervical and vestibular signals processing, but, in the present experiment, the
      vestibular output was the only signal that had the potentiality to contribute to
      accurate coding of the target position after simultaneous head and trunk
      movements. Our results therefore suggest that the vestibular output is a noisy
      signal for the central nervous signal to update the visual space during head-in
      space motion.

PMID- 9772117
TI  - Encoding target-trunk relative position: cervical versus vestibular contribution.
AB  - The contribution of cervical and vestibular cues in signaling the changes in
      target-trunk relative positions during self-motion was investigated. Normal
      subjects (Ss) were shown a LED flashed in the peripheral visual field in a dark
      room. Ss were then passively rotated about the vertical axis in one of three
      different conditions: (1) head chair-fixed (vestibular condition); (2) head earth
      fixed (relaxed neck condition); and (3) head earth-fixed, but with the Ss
      actively attempting to turn it (activated neck condition). The Ss were then
      required to indicate, with their unseen index finger, the position of the
      previously flashed target. It was found that pointing at the memorized target was
      similarly accurate in the relaxed neck condition and in the activated neck
      condition. In the vestibular condition, pointing accuracy dropped significantly.
      These results suggest that neck proprioceptive signals are more effective than
      vestibular ones in signaling relative changes in the position of stationary
      objects with respect to the body during head-trunk motion. The finding that
      cervically mediated estimates were unchanged during active contraction of the
      neck muscles may suggests that efference copy signals may help interpret the
      change in the afferent signals caused by voluntary neck muscle activation.

PMID- 9772118
TI  - Disorders of visuospatial orientation in the frontal plane in patients with
      visual neglect following right or left parietal lesions.
AB  - Current models of spatial neglect focus on deficits in the patients' horizontal
      or midsagittal plane. However, other evidence suggests that patients with temporo
      parietal lesions centered on the parieto-insular-vestibular cortex show disturbed
      spatial perception of the subjective visual vertical and oblique orientation
      discrimination in another spatial plane, the frontal plane. As the relationship
      between neglect and spatial orientation deficits is unclear, we examined how
      patients with and without visual neglect perform visuospatial tasks in the roll
      plane and how their performance is related to neglect. Thirteen patients with
      predominantly right parietal lesions and left-sided neglect, 14 control patients
      without neglect after right-hemispheric cerebral lesions (RBD-controls), 11
      patients without neglect after left-hemispheric lesions (LBD-controls), 3
      patients with right-sided neglect after left parietal lesions, and 12 normal
      subjects were investigated. Constant errors and difference thresholds were
      measured with a PC-based system when the subjects had to adjust a luminous line
      to their subjective visual vertical, subjective visual horizontal, and in
      relation to an obliquely oriented reference line. Subjects were oriented with
      their head and body earth-vertical while sitting in a chair in total darkness.
      Patients with left-sided as well as those with right-sided neglect showed a
      significant, in most cases contraversive, tilt of the three spatial orientations
      (about 5 degrees counterclockwise in the left neglect group and 5.5 degrees-8.5
      degrees clockwise in the right neglect group). In contrast, the two patient
      groups without neglect as well as the normal subjects showed nearly perfect
      visuospatial judgements with constant errors of less than 0.8 degrees .
      Difference thresholds were significantly elevated in patients with left neglect
      and in two of three patients with right-sided neglect, whereas normal control
      subjects and both control patient groups without neglect performed
      indistinguishably, having thresholds of one-tenth of those of the neglect
      patients. Tilt of all three spatial axes was significantly related to the
      severity of neglect (mean r for unsigned errors, 0.74; for difference thresholds,
      0.40), indicating a significant contribution to the symptomatology of left and
      right spatial neglect. These results indicate a close although not necessarily
      causal link between spatial orientation deficits in the frontal plane and
      hemispatial neglect in patients with left or right parietal lesions, surpassing
      the well-documented impairments of these patients in the horizontal plane.

PMID- 9772119
TI  - Monotherapy with dextromethorphan or tirilazad--but not a combination of both-
      improves outcome after transient focal cerebral ischemia in rats.
AB  - Cell death after cerebral ischemia is mediated by a massive release of excitatory
      amino acids, generation of free radicals, and - a crucial step - calcium influx
      into cells. We examined the hypothesis that concurrent administration of drugs
      ameliorating brain damage via different mechanisms would result in a synergistic
      neuroprotective effect. The neuroprotective efficacy of two clinically available
      drugs - the N-methyl-D-aspartate and calcium-channel antagonist dextromethorphan
      (DM) and the antioxidant tirilazad - were studied in monotherapy and in
      combination in a rat model of transient focal ischemia. Male Sprague-Dawley rats
      were subjected to 90 min of middle-cerebral-artery occlusion by an intraluminal
      filament technique. The animals were randomly assigned to one of four treatments
      (n=10 each): (1) vehicle-treated controls, (2) DM, (3) tirilazad, (4)
      DM+tirilazad. Drugs or vehicles were administered 15 min before ischemia and at
      reperfusion. Local cerebral blood flow (LCBF) was bilaterally recorded by
      continuous laser Doppler flowmetry. Functional deficits were quantified by daily
      neurological examinations. Infarct volume was assessed planimetrically after 7
      days. DM prevented post-ischemic hypoperfusion. Tirilazad did not influence LCBF.
      Monotherapy with DM or tirilazad improved neurological function and reduced
      infarct volume by 45% and 48%, respectively. Combination therapy failed to
      influence neurological recovery and infarct volume. Although, from
      pharmacological point of view, a synergistic neuroprotective effect is expected,
      combination of dextromethorphan and tirilazad may lead to mutual inhibition or
      potentiate adverse effects.

PMID- 9772120
TI  - The marginal nuclei of the spinal cord in turtles: neuron assemblies in which
      gamma-aminobutyric acid and nitric oxide synthase are colocalized.
AB  - Conspicuous nerve-cell assemblies, identified as the marginal nuclei described in
      other sauropsidans, were found all along the spinal cord of turtles. gamma
      aminobutyric acid (GABA) and nitric oxide synthase (NOS) activities were
      colocalized within these neurons, which also reacted positively to reduced
      nicotinamide adenine dinucleotide phosphate-diaphorase stains. The marginal
      nuclei neurons may, thus, play an inhibitory function mediated by their GABA
      terminals and a long-distance modulatory function mediated by NO liberation.

PMID- 9772121
TI  - Soy protein, isoflavones and cardiovascular disease risk.
AB  - Since the early 1940s, scientists have examined the effect of soy protein on
      blood cholesterol concentrations. Although studies in animals have suggested that
      soy protein lowers blood cholesterol concentrations, similar studies in humans
      have yielded less consistent results. The presence or absence of the soybean
      isoflavone fraction may be a confounding factor. This fraction, consisting
      primarily of genistein, daidzein and glycetein, has been shown to have a
      hypocholesterolemic effect in animals and humans. Potential mechanisms by which
      soy protein and/or isoflavones induce lowering of blood cholesterol
      concentrations include thyroid status, bile acid balance and the estrogenic
      effects of genistein and daidzein. Some studies have suggested that isoflavones
      exhibit antioxidant properties and have favorable effects on arterial compliance.
      In addition to the aforementioned potential beneficial effects, the increased
      consumption of products containing soy protein may displace foods relatively high
      in saturated fat and cholesterol from the diet and hence have an indirect blood
      cholesterol-lowering effect.

PMID- 9772123
TI  - Constance V. Kies (1934-1993).

PMID- 9772122
TI  - Vitamin E and atherosclerosis.
AB  - Vitamin E was advocated as an effective treatment for heart disease by Dr. Even
      Shute of London, Ontario more than 50 years ago. His pioneering claims, which
      were unacceptable to the medical community at large, have been confirmed by
      recent findings from epidemiologic studies and clinical trials. This review
      integrates our current knowledge of atherogenesis with the biological functions
      of vitamin E. The response-to-injury hypothesis explains atherosclerosis as a
      chronic inflammatory response to injury of the endothelium, which leads to
      complex cellular and molecular interactions among cells derived from the
      endothelium, smooth muscle and several blood cell components. Inflammatory and
      other stimuli trigger an overproduction of free radicals, which promote
      peroxidation of lipids in LDL trapped in the subendothelial space. Products of
      LDL oxidation are bioactive, and they induce endothelial expression and secretion
      of cytokines, growth factors and several cell surface adhesion molecules. The
      last-mentioned are capable of recruiting circulating monocytes and T lymphocytes
      into the intima where monocytes are differentiated into macrophages, the
      precursor of foam cells. In response to the growth factors and cytokines, smooth
      muscle cells proliferate in the intima, resulting in the narrowing of the lumen.
      Oxidized LDL can also inhibit endothelial production of prostacyclin and nitric
      oxide, two potent autacoids that are vasodilators and inhibitors of platelet
      aggregation. Evidence is presented that vitamin E is protective against the
      development of atherosclerosis. Vitamin E enrichment has been shown to retard LDL
      oxidation, inhibit the proliferation of smooth muscle cells, inhibit platelet
      adhesion and aggregation, inhibit the expression and function of adhesion
      molecules, attenuate the synthesis of leukotrienes and potentiate the release of
      prostacyclin through up-regulating the expression of cytosolic phospholipase A2
      and cyclooxygenase. Collectively, these biological functions of vitamin E may
      account for its protection against the development of atherosclerosis.

PMID- 9772124
TI  - Zinc deprivation of murine 3T3 cells by use of diethylenetrinitrilopentaacetate
      impairs DNA synthesis upon stimulation with insulin-like growth factor-1 (IGF-1).
AB  - Growth failure in zinc-deficient animals is associated with decreased DNA
      synthesis; zinc deprivation of 3T3 cells, by use of
      diethylenetrinitrilopentaacetate (DTPA), impairs thymidine incorporation when the
      cells are stimulated with fetal bovine serum (FBS). The purpose of this study was
      to determine the step of cell cycle progression that is affected by zinc
      deprivation. Swiss murine 3T3 cells were cultured for 3 d in complete media and
      then for 2 d in low serum media. Cells were then placed in serum-free media and
      stimulated in sequence with platelet-derived growth factor (PDGF; 3 h), epidermal
      growth factor (EGF; 0.5 h) and insulin-like growth factor-I (IGF-I; 16 h). The
      combination of growth factors stimulated thymidine incorporation to the same
      extent as 10% FBS, and DTPA or EDTA (0.6 mmol/L) inhibited thymidine
      incorporation. Inhibition was prevented by addition of zinc, but not calcium,
      iron or cadmium (0.4 mmol/L). When DTPA was present during all stages with no
      addition of zinc, or zinc added during the competency-priming (PDGF and EGF)
      step, the IGF-I step, or both steps, the zinc effect occurred at the IGF-I step.
      Zinc addition 4 h before the measurement of thymidine incorporation had no
      ameliorative effect, but the presence of zinc during the prior 12 h increased
      incorporation. Thus zinc exerts its major effect on DNA synthesis during the IGF
      I stimulatory phase of the cell cycle. The total zinc concentration of 3T3 cells
      treated with DTPA for 16 h was not different from that of untreated cells; hence
      only a small compartment of the cell is affected by DTPA.

PMID- 9772125
TI  - The effects of a high fat diet on leptin mRNA, serum leptin and the response to
      leptin are not altered in a rat strain susceptible to high fat diet-induced
      obesity.
AB  - Osborne-Mendel (OM) and S5B/Pl rats differ in their sensitivity to develop
      obesity when fed a high fat (HF) diet; OM rats become obese, whereas S5B/Pl rats
      remain thin. We have investigated the possibilities that either an impaired
      leptin response or resistance to leptin action underlies the sensitivity to this
      form of obesity in OM rats. In Experiment 1, OM and S5B/Pl rats fed a nonpurified
      diet were killed at d 0 or were fed either a HF (56% fat energy) or a low fat
      (LF, 10% fat energy) diet for 2 or 7 d. The HF diet increased serum leptin
      significantly by d 2 to levels that were similar in both rat strains. At 7 d,
      leptin levels were lower than at d 2 but remained higher than levels in the d 0
      control groups. The leptin mRNA:18S RNA ratio in epididymal adipose tissue
      increased to higher levels in HF-fed OM rats than in S5B/Pl rats fed that diet.
      However, although the LF diet had no effect in S5B/Pl rats, it increased leptin
      mRNA levels in epididymal adipose tissue of OM rats compared with the controls
      fed the nonpurified diet. In Experiment 2, OM and S5B/Pl rats were fed HF or LF
      diets for 5 wk. At that time, their feeding response to a range of leptin doses
      (0, 1, 5 or 10 microgram) given intracerebroventricularly was tested after
      overnight food deprivation. There was a similar dose-dependent reduction in
      energy intake in response to leptin in both OM and S5B/Pl rats. These responses
      were independent of the diet. The data suggest that the susceptibility of OM rats
      to HF diet-induced obesity is not related to either a loss of central sensitivity
      to leptin or a failure to enhance leptin production acutely, although the failure
      to maintain chronically increased levels of serum leptin could contribute to the
      obesity.

PMID- 9772126
TI  - beta-carotene 15,15'-dioxygenase activity and cellular retinol-binding protein
      type II level are enhanced by dietary unsaturated triacylglycerols in rat
      intestines.
AB  - The purpose of this study was to examine effects of dietary triacylglycerols on
      beta-carotene 15,15'-dioxygenase (EC 1.13.11.21) activity and cellular retinol
      binding protein [CRBP (II)] in rats. Six groups of eight rats (7-wk old) were fed
      one of the following diets: standard (STD; 2.5% soybean oil), saturated (SFA; 15%
      hydrogenated soybean oil), monounsaturated (MUFA; 15% olive oil), polyunsaturated
      (PUFA; 15% soybean oil) or clofibrate (CLF; 2.5% soybean oil + 0.2% clofibrate)
      for 3 wk. The dioxygenase specific activities of the intestinal homogenates in
      the MUFA and PUFA groups fed the high fat diets were 2.4 times that of the STD
      group fed a low fat diet (P < 0.01), whereas the activities of the SFA and CLF
      groups were not significantly different from that of the STD group. The level of
      CRBP (II) in the intestine of the PUFA group was 1. 3-fold that of the STD group
      (P < 0.05), whereas there were no significant differences among the other groups.
      In a second experiment, the dioxygenase activity of rat intestine was followed
      over 3 wk of feeding the STD and PUFA diets. After the PUFA diet was consumed for
      1 d, the activity was enhanced to 2.7 times the baseline level and remained
      thereafter at that high level, whereas the activity of the STD group remained at
      the low baseline level. Thus, dietary polyunsaturated triacylglycerols enhanced
      both beta-carotene 15,15'-dioxygenase activity and CRBP (II) level in rat
      intestine. These results suggest that the dioxygenase and CRBP (II) are regulated
      by the same mechanism involving long-chain fatty acids and their metabolites.

PMID- 9772127
TI  - Variations in dietary fat and cholesterol intakes modify antioxidant status of
      SHR and WKY rats.
AB  - The effects of varying dietary fat saturation [butter (B), beef tallow (BT)] or
      polyunsaturation [(n-6) soybean oil (SBO), (n-3) menhaden oil (MO)] and
      cholesterol content (0.05 and 0.5 g/100 g) on systolic blood pressure (SBP),
      plasma lipids and tissue antioxidant status were investigated in 14-wk-old
      spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats.
      Varying dietary fat composition for 9 wk had no influence on SBP in either SHR or
      WKY rats. Rats fed MO diets exhibited smaller (P < 0.05) body weight gains, lower
      (P < 0.05) feed efficiency ratios and lower (P < 0.05) plasma cholesterol
      concentrations than those fed the B, BT and SBO diets. Significant (P < 0.05)
      interactions for animal strain x cholesterol intake and animal strain x fat
      source were noted for serum cholesterol concentrations. SHR exhibited higher (P <
      0.05) RBC and liver catalase (CAT), and heart and liver superoxide dismutase
      (SOD) activities similar to those of WKY rats. The lower (P <0.01) RBC, heart and
      liver glutathione peroxidase (GSH-Px) activities observed in SHR coincided with
      higher (P <0.01) glutathione reductase (GSSG-Red), compared with WKY rats.
      Dietary cholesterol intake had no effect on RBC, heart and liver total sulfhydryl
      concentration or GSH-Px activities, but increased (P <0. 001) liver GSSG-Red.
      Feeding MO resulted in lower (P <0.001) RBC and heart GSH-Px activities. In
      contrast, feeding B and BT resulted in lower GSH-Px in liver. The significant (P
      < 0.01) animal strain x fat source interaction obtained for liver GSH-Px activity
      indicated that SHR responded differently to polyunsaturated fatty acid feeding
      than their WKY counterparts. Diet-induced changes in tissue antioxidant status
      were tissue specific and did not affect the development of hypertension in SHR.

PMID- 9772128
TI  - Hepatic histidase gene expression responds to protein rehabilitation in
      undernourished growing rats.
AB  - We studied the effect of nutritional rehabilitation with a 6, 18 or 50% casein
      diet in undernourished rats on histidase (Hal) expression. Undernutrition was
      induced by feeding rats a 0.5% casein diet for 5 wk. Over this period, growth,
      serum total proteins and insulin-like growth factor-I (IGF-I) levels were
      significantly lower than those of rats that freely consumed an 18% casein diet.
      During this period, undernutrition also significantly reduced Hal activity and
      Hal-mRNA concentration. Nutritional rehabilitation for 21 d with a 6% casein diet
      did not change any of these variables. Nutritional rehabilitation with an 18 or
      50% casein diet for 1 d initiated the restoration of Hal activity and mRNA
      concentration. After 10 d of consuming 18 or 50% casein diets, Hal activity was 5
      and 14-fold, and mRNA concentration was 8.5- and 23-fold higher, respectively,
      than in the protein-undernourished group (PU). During this period, body weight,
      total serum proteins and IGF-I levels were also significantly (P < 0.05) higher
      than those of the PU group. At the end of 21 d of rehabilitation with an 18 or
      50% casein diet, Hal activity was 14- and 31-fold higher and Hal mRNA
      concentration was 10- and 24-fold higher, respectively, than in the PU group. In
      conclusion, our data showed that rehabilitation of undernourished rats with a 6%
      casein diet was not sufficient to re-establish growth indicators, Hal activity or
      gene expression, and that nutritional rehabilitation with an 18 or 50% casein
      diet effectively re-established body weight , biochemical variables and the
      capacity of histidase gene expression to eliminate the excess of protein.

PMID- 9772130
TI  - Protein deficiency and nutritional recovery modulate insulin secretion and the
      early steps of insulin action in rats.
AB  - Maternal malnutrition was shown to affect early growth and leads to permanent
      alterations in insulin secretion and sensitivity of offspring. In addition,
      epidemiological studies showed an association between low birth weight and
      glucose intolerance in adult life. To understand these interactions better, we
      investigated the insulin secretion by isolated islets and the early events
      related to insulin action in the hind-limb muscle of adult rats fed a diet of 17%
      protein (control) or 6% protein [low (LP) protein] during fetal life, suckling
      and after weaning, and in rats receiving 6% protein during fetal life and
      suckling followed by a 17% protein diet after weaning (recovered). The basal and
      maximal insulin secretion by islets from rats fed LP diet and the basal release
      by islets from recovered rats were significantly lower than that of control rats.
      The dose-response curves to glucose of islets from LP and recovered groups were
      shifted to the right compared to control islets, with the half-maximal response
      (EC50) occurring at 16.9 +/- 1.3, 12.4 +/- 0.5 and 8.4 +/- 0.1 mmol/L,
      respectively. The levels of insulin receptor, as well as insulin receptor
      substrate-1 and phosphorylation and the association between insulin receptor
      substrate-1 and phosphatidylinositol 3-kinase were greater in rats fed a LP diet
      than in control rats. In recovered rats, these variables were not significantly
      different from those of the other two groups. These results suggest that glucose
      homeostasis is maintained in LP and recovered rats by an increased sensitivity to
      insulin as a result of alterations in the early steps of the insulin signal
      transduction pathway.

PMID- 9772129
TI  - Early weaning induces jejunal ornithine decarboxylase and cell proliferation in
      neonatal rats.
AB  - Increased ornithine decarboxylase (ODC) activity is associated with rapid cell
      proliferation in many cell types. The cellular effects of early weaning on
      intestinal development are not well established. To investigate whether ODC is
      involved in intestinal growth after early weaning, we precociously weaned
      suckling rats on postnatal d 15 and followed through d 21 (6 d after early
      weaning). Age-matched suckling pups served as controls. Rat pups were killed 1,
      2, 3 and 6 d after early weaning and jejunal mucosa was assayed for ODC and
      sucrase activities, and protein and DNA contents. Jejunal cell proliferation was
      monitored by bromodeoxyuridine immunohistochemistry. Elevated jejunal ODC
      activity 1 d after early weaning was the earliest cellular event that was
      detected in the current study. ODC activity peaked at d 3 (about 15-fold greater
      than age-matched unweaned suckling controls). Sucrase activity was elevated at d
      2 after weaning and peaked at d 3 (about 10-fold greater than controls). Greater
      bromodeoxyuridine immunostaining in early weaned rats occurred on d 3. Protein
      and DNA contents were greater in jejunal mucosa of early weaned rats at d 6.
      Serum corticosterone levels were elevated on d 1 and d 2 after early weaning
      compared to controls. To explore whether the intake of nonpurified diet played a
      role, we also compared the induction of jejunal ODC activity in early weaned pups
      and pups that were food-deprived for 1 d. ODC activity was not greater in the
      food-deprived group compared to suckling controls while the early weaned group
      had 6-fold greater activity 1 d after early weaning. Early weaning stimulates
      jejunal cell proliferation and differentiation. The temporal sequence of
      increased ODC activity followed by increases in other growth variables suggests
      that the induction of ODC activity may act as an early marker of intestinal
      growth during early weaning.

PMID- 9772131
TI  - Dietary lutein from marigold extract inhibits mammary tumor development in BALB/c
      mice.
AB  - High levels of dietary lutein can inhibit mammary tumor growth in mice. However,
      the antitumor effect of low levels of dietary lutein on mammary tumors is
      unavailable. Female BALB/c mice and the WAZ-2T (-SA) mammary tumor cell line were
      used in two experiments. A preliminary tumor cell dose titration study
      (Experiment 1) was designed to determine the inoculation dose to produce
      approximately 65% tumor incidence. Mice (n = 10/dose) were inoculated with 0 to 1
      x 10(6) tumor cells in the right inguinal mammary fat pad. A tumor cell load of
      2.5 x 10(3) cells/inoculation produced approximately 65% tumor incidence. This
      dose was used in a subsequent study (Experiment 2) of the efficacy of dietary
      lutein against mammary tumor development. Mice (n = 20/treatment) were fed a
      semisynthetic diet containing 0, 0.002, 0.02, 0.2 or 0.4% lutein from marigold
      extract. After 14 d, all mice were inoculated with 2.5 x 10(3) tumor cells, and
      tumor growth was measured daily for 70 d at which time blood, liver, spleen and
      tumors were obtained. Lutein + zeaxanthin uptake increased dose-dependently (P <
      0.05) with dietary lutein levels from 0 to 0.02% (spleen) or 0.2% (plasma, liver
      and tumor). Low levels (0.002 and 0.02%) of dietary lutein lowered (P < 0.05)
      mammary tumor incidence, tumor growth and lipid peroxidation, and increased tumor
      latency, whereas higher dietary levels (0.2 or 0.4%) were less effective.
      Therefore, very low amounts of dietary lutein (0.002%) can efficiently decrease
      mammary tumor development and growth in mice.

PMID- 9772132
TI  - Pretreatment of young pigs with vitamin E attenuates the elevation in plasma
      interleukin-6 and cortisol caused by a challenge dose of lipopolysaccharide.
AB  - The effect of a short-term, high-dose intramuscular injection of d-alpha
      tocopherol was studied in pigs given a challenge dose of lipopolysaccharide
      (LPS). Twenty-four pigs surgically fitted with jugular catheters were used in a 2
      x 2 factorial design. Pigs received either 0 or 600 mg d-alpha-tocopherol by
      intramuscular injection for 3 d before receiving an intraperitoneal injection of
      saline containing either 0 or 5 microgram/kg body weight Escherichia coli LPS.
      Blood was collected from indwelling jugular catheters at 0, 1, 2, 4, 6, 8, 12 and
      24 h after injection of LPS. Plasma alpha-tocopherol levels were 13-fold greater
      (P < 0.01) at time 0 in pigs pretreated with 600 mg d-alpha-tocopherol (9.9 +/-
      1.3 mg/L) than in those not treated with d-alpha-tocopherol (0.74 +/- 0.09 mg/L).
      Injection of LPS increased (P < 0.05) plasma levels of interleukin-6 (IL-6) and
      cortisol at 2-h postinjection, regardless of vitamin E treatment. However, pigs
      that received alpha-tocopherol before the LPS challenge had substantially lower
      (P < 0.05) peak levels of IL-6 and cortisol than pigs not receiving alpha
      tocopherol. These results suggest that supplementation with a surfeit level of
      vitamin E reduces the response of pigs to endotoxin.

PMID- 9772133
TI  - Vitamin A inhibits radiation-induced pneumonitis in rats.
AB  - Radiation-induced lung injury frequently limits the total dose of thoracic
      radiotherapy that can be delivered, and the determinants of host susceptibility
      are poorly understood. To test the hypothesis that vitamin A status may be an
      important, modifiable host determinant of radiation-induced lung injury, we
      determined the effect of altered vitamin A status on radiation-induced lung
      inflammation in rats. WAG-Rij Y rats were fed a diet deficient in or supplemented
      with vitamin A (0 units/kg or 80,000 units/kg diet). After 5 wk of consuming the
      prescribed diet, rats were irradiated with 15 Gy of 250 kV X-rays to the whole
      thorax. At 4-5 wk post-irradiation, there were significantly fewer neutrophils on
      bronchoalveolar lavage in rats fed the vitamin A-supplemented diet (8.8 +/- 1.2%
      neutrophils) compared with those fed the vitamin A-deficient diet (20.8 +/- 3.4%
      neutrophils, P < 0.01). At the termination of the experiment, 4-5 wk
      postradiation, lung retinol levels of the vitamin A-supplemented group were 19.6
      +/- 1.8 nmol/g, whereas those in the vitamin A-deficient group were significantly
      lower, 1.7 +/- 0.5 nmol/g (P < 0.01). These findings suggest that supplemental
      vitamin A may reduce lung inflammation after thoracic radiation and be an
      important modifiable radioprotective agent in the lung.

PMID- 9772134
TI  - A three-day weighed food record and a semiquantitative food-frequency
      questionnaire are valid measures for assessing the folate and vitamin B-12
      intakes of women aged 16 to 19 years.
AB  - The purpose of this study was to validate a food-frequency questionnaire (FFQ)
      and a 3-d weighed food record (3d-WFR) by comparing nutrient intakes estimated
      using these methods with serum folate, RBC folate and serum vitamin B-12
      concentrations in 105 females aged 16-19 y. During an early morning clinic visit,
      subjects completed a self-administered, 116-item FFQ, blood was collected and
      they were trained to complete a 3d-WFR. Folate intakes as determined by the 3d
      WFR (r = 0.65, P < 0.01) exhibited a stronger association with serum folate than
      did intakes from the FFQ (r = 0.48, P < 0.01) (P = 0.017). The correlations
      between folate intakes and RBC folate as determined by the FFQ (r = 0.42, P <
      0.01) and 3d-WFR (r = 0.50, P < 0.01) methods did not differ. Vitamin B-12
      intakes showed only a modest association with serum vitamin B-12 when supplement
      users were included in the analyses (FFQ, r = 0.25, P < 0.05; 3d-WFR, r = 0.32, P
      < 0.05). After excluding supplement users from the analyses, the relationship
      between vitamin B-12 intakes as determined by FFQ and serum vitamin B-12 was no
      longer significant. Median daily folate intakes (346 vs. 212 microgram) and
      vitamin B-12 (4.9 vs. 1.9 microgram) estimated from the FFQ were higher than
      those obtained from the 3d-WFR. In sum, these data suggest that both the FFQ and
      3d-WFR are valid measures of assessing the folate intake of young women, and both
      appear to be useful in determining vitamin B-12 intake when supplemental users
      are included. The markedly different conclusions about absolute folate and
      vitamin B-12 intakes obtained using these two dietary methodologies should be
      taken into consideration when making recommendations about optimal folate intakes
      in relation to disease prevention.

PMID- 9772135
TI  - Maternal nutritional status is inversely associated with lactational amenorrhea
      in Sub-Saharan Africa: results from demographic and health surveys II and III.
AB  - Breast-feeding is positively associated with the duration of postpartum
      amenorrhea; thus it is a major determinant of fertility in countries where
      effective contraceptive methods are not widely available. The objective of these
      analyses was to examine the association between maternal nutritional status and
      lactational amenorrhea (LA) among breast-feeding women. Women who were not
      pregnant, who were breast-feeding, who were not using hormonal contraceptives and
      who had a child </=2 y old at the time of survey were included in the analyses.
      Multivariate logistic regression was used to examine this association with the
      use of Demographic and Health Surveys data collected in seven Sub-Saharan African
      countries between 1990 and 1994. Analyses were adjusted for nine confounders,
      including breast-feeding behavior, child nutritional status and child age. Within
      country analyses consistently showed the trend of low maternal body mass index
      (BMI) associated with a higher likelihood of being amenorrheic. Pooled analyses
      (n = 9839) were performed using two child age groups (<9 mo and 9-24 mo). The <9
      mo pooled analysis showed that women with BMI < 18.5 kg/m2 (odds ratio; 95%
      confidence interval: 1.6; 1.2-2.3) were more likely to remain amenorrheic at the
      time of the survey than their "better-nourished" counterparts. The 9-24 mo pooled
      analysis showed that the differential probability of being amenorrheic between
      undernourished and "better-nourished" women increased with time postpartum, where
      the adjusted difference in the median duration of amenorrhea associated with
      maternal nutritional status among breast-feeding women was 1.4 mo. These results
      suggest that maternal nutritional status plays an independent role in the return
      of ovulation after delivery.

PMID- 9772136
TI  - A low molar ratio of retinol binding protein to transthyretin indicates vitamin A
      deficiency during inflammation: studies in rats and a posterior analysis of
      vitamin A-supplemented children with measles.
AB  - To assess whether the molar ratio of retinol-binding protein (RBP) to
      transthyretin (TTR) is of utility in detecting vitamin A (VA) deficiency during
      inflammation, we analyzed data from a rat model of endotoxin-induced inflammation
      and from a previously reported randomized, placebo-controlled trial of VA
      supplementation in children with acute measles. In rats, both marginal VA
      deficiency and inflammation were independent causes of low plasma RBP (two-way
      ANOVA, P < 0.001), whereas plasma TTR concentration was reduced only by
      inflammation (P < 0.001). The molar ratio of plasma RBP to TTR was reduced (by
      approximately 50%) only in rats with marginal VA deficiency and inflammation (two
      way ANOVA interaction, P < 0.01). Serum retinol concentration, C-reactive protein
      (CRP, an indicator of inflammation) and the RBP:TTR molar ratio were determined
      in children with acute measles at baseline and 2 wk after subgroups received a
      placebo or a 210 micromol VA supplement. The ratio of RBP:TTR was selectively
      reduced in children in the placebo group with low plasma retinol (<0.35
      micromol/L) and elevated CRP (>40 mg/L). In children with a low RBP:TTR molar
      ratio (<0.30) at baseline, the RBP:TTR ratio increased significantly 2 wk later
      only in the VA-treated subgroup. These analyses provide evidence that, because
      RBP is differentially reduced in comparison to TTR during VA deficiency, the
      combined determination of the concentrations of serum RBP and TTR may provide a
      promising means of detecting VA deficiency during inflammation.

PMID- 9772137
TI  - Increased height gain of children fed a high-protein diet during convalescence
      from shigellosis: a six-month follow-Up study.
AB  - The impact of dietary supplementation on catch-up growth was evaluated in 69
      malnourished children ages 24-60 mo after recovery from shigellosis. They were
      fed either a high-protein (HP) diet with 15% of energy as protein, or a standard
      protein (SP) diet with 7.5% energy as protein, for 3 wk in a metabolic study
      ward. Children were followed up bi-weekly for 6 mo by trained health assistants
      when anthropometric measurements and information of any illness were collected.
      Thirty-one children in the HP group and 28 children in the SP group completed 6
      mo follow-up. The increase in height (mean +/- SD) was 5.3 +/- 1.0 cm vs. 4.1 +/-
      1.1 cm for HP and SP groups, respectively (P < 0.001), whereas increase in body
      weight was 1.39 +/- 0.58 and 1.29 +/- 0.72 kg for children fed HP and SP,
      respectively (P = 0.59). The proportion of children who were severely stunted (< 
      2 SD height-for-age) decreased from 45 to 29% in the HP group compared to 50 to
      46% in the SP group (P < 0.05) at 6-mo follow-up. The number of diarrheal
      episodes per child tended to be lower in the HP vs. SP than in the SP group (1.9
      vs. 2.3, P = 0.41). These results demonstrate that feeding an HP diet to the
      malnourished children during recovery from shigellosis enhanced linear growth
      with a modest reduction in diarrheal morbidity during the 6-mo follow-up period.

PMID- 9772138
TI  - Impact of food supplementation during lactation on infant breast-milk intake and
      on the proportion of infants exclusively breast-fed.
AB  - To evaluate whether milk production can be improved by increasing food intake, a
      randomized, double-blind, supplementation trial was completed among 102 lactating
      Guatemalan women. The subjects were undernourished, as indicated by their low
      values for calf circumference (CC) and the small size of their infants at birth.
      A high-energy (2.14 MJ/d, HES) and a low-energy (0.50 MJ/d, LES) supplement were
      distributed 6 d/wk from wk 5 to 25 of lactation. Data were evaluated using
      repeated-measures analysis of variance on the increments from initial values for
      each outcome variable with one-tailed tests of statistical significance. The
      maternal energy intake increased 1.18 MJ/d (P < 0.01) more among the HES than the
      LES women. Benefit from supplementation was more evident among the more
      undernourished (CC </= median value, 29.5 cm) women. Among these 53 lower-CC
      women, infant milk and milk energy intakes were 10% higher (64 g/d and 14 MJ/d,
      respectively, at wk 25) in the HES than the LES group. After controlling for
      other determinants of infant milk and energy intakes in regression analyses, the
      significance of these differences increased to P < 0.04. However, there was no
      detectable effect on infant growth. Logistic regression analysis was used to show
      that HES women were significantly (P < 0.05) more likely than LES women to be
      exclusively breast-feeding their infants at wk 20, the time when the effect of
      supplementation was most evident. These findings establish that milk production
      and the duration of exclusive breast-feeding of undernourished women can be
      improved with the provision of supplemental food.

PMID- 9772139
TI  - Varying dietary fat type of reduced-fat diets has little effect on the
      susceptibility of LDL to oxidative modification in moderately
      hypercholesterolemic subjects.
AB  - The effect of the fatty acid composition of reduced-fat diets on the in vitro
      oxidation of LDL was examined in 14 moderately hypercholesterolemic [low density
      lipoprotein (LDL) > 3.36 mmol/L] postmenopausal female and male subjects (age 44
      78 y). Each subject consumed each of five reduced-fat diets [30 energy percent
      (E%) fat, 17 E% protein and 53 E% carbohydrate] enriched in beef tallow, canola
      oil, corn oil, olive oil or rice bran oil (20 E%) for 32-d periods. In vitro
      oxidation of LDL was assessed by incubating LDL with hemin and hydrogen peroxide,
      and measuring the time required for the reaction to reach maximum velocity (lag
      time). LDL lag times were 93.2 +/- 25.8, 95.9 +/- 26.4, 104.2 +/- 32.7, 108.0 +/-
      26.6 and 113.1 +/- 24.0 min for corn oil, beef tallow, rice bran oil, canola oil
      and olive oil periods, respectively. When the data from all dietary phases were
      pooled, LDL alpha-tocopherol level (r = 0.30, P = 0.01) and plasma 18:1/18:2
      ratio (r = 0.22, P = 0.08) were positively related to resistance of LDL to
      oxidation. Differences induced by the dietary perturbations in LDL content of
      beta-cryptoxanthin, lutein/zeaxanthin, lycopene, alpha-carotene or beta-carotene,
      and LDL particle size were not related to resistance of LDL to oxidation. In
      conclusion, in middle-aged and elderly moderately hypercholesterolemic subjects,
      the consumption of reduced-fat diets enriched in animal fat or vegetable oils
      with a relatively wide range of fatty acid profiles did not alter the in vitro
      susceptibility of LDL to oxidation. The advantages of reducing the saturated fat
      content of the diet were reflected in lower total and LDL cholesterol levels.

PMID- 9772141
TI  - Digestibility of cooked and raw egg protein in humans as assessed by stable
      isotope techniques.
AB  - Egg proteins contribute substantially to the daily nitrogen allowances in Western
      countries and are generally considered to be highly digestible. However,
      information is lacking on the true ileal digestibility of either raw or cooked
      egg protein. The recent availability of stable isotope-labeled egg protein
      allowed determination of the true ileal digestibility of egg protein by means of
      noninvasive tracer techniques. Five ileostomy patients were studied, once after
      ingestion of a test meal consisting of 25 g of cooked 13C- and 15N-labeled egg
      protein, and once after ingestion of the same test meal in raw form. Ileal
      effluents and breath samples were collected at regular intervals after
      consumption of the test meal and analyzed for 15N- and 13C-content, respectively.
      The true ileal digestibility of cooked and raw egg protein amounted to 90.9 +/-
      0.8 and 51.3 +/- 9.8%, respectively. A significant negative correlation (r = 
      0.92, P < 0.001) was found between the 13C-recovery in breath and the recovery of
      exogenous N in the ileal effluents. In summary, using the 15N-dilution technique
      we demonstrated that the assimilation of cooked egg protein is efficient, albeit
      incomplete, and that the true ileal digestibility of egg protein is significantly
      enhanced by heat-pretreatment. A simple 13C-breath test technique furthermore
      proved to be a suitable alternative for the evaluation of the true ileal
      digestibility of egg protein.

PMID- 9772140
TI  - Pharmacokinetics of soybean isoflavones in plasma, urine and feces of men after
      ingestion of 60 g baked soybean powder (kinako).
AB  - To take advantage of the various pharmacologic activities of soy bean
      isoflavones, more detailed studies of the absorption and excretion rates of these
      compounds in humans and subsequent evaluation of their bioavailabilities are
      required. We conducted a pharmacokinetic study of soybean isoflavones in seven
      healthy male volunteers. After ingestion of 60 g of kinako (baked soybean powder,
      containing 103 micromol daidzein and 112 micromol genistein), changes of the
      isoflavone and metabolite concentrations in plasma, urine and feces were measured
      by gas chromatography-mass spectrometry. The plasma concentration of genistein
      increased after 2 h and reached its highest value of 2.44 +/- 0.65 micromol/L 6 h
      later. The plasma concentration of daidzein peaked at 1.56 +/- 0.34 micromol/L at
      the same time, but it was always lower than that of genistein. Peak plasma
      concentration of O-desmethylangolensin (O-DMA) and equol appeared after the
      daidzein peak in four and two subjects, respectively. In contrast with plasma,
      daidzein was the main component in urine. Urinary daidzein excretion started to
      increase shortly after the rise in its plasma concentration and reached 2.4
      micromol/h 8 h after ingestion of kinako. Genistein excretion in urine paralleled
      that of daidzein, but the value at 6 h was about half (1.1 micromol/h). The
      majority of ingested isoflavones after ingestion of kinako were recovered on d 2
      or 3 in the feces. Total recovery of daidzein, O-DMA and equol from urine and
      feces was 54.7%, calculated from daidzein intake; 20.1% of administered genistein
      was recovered as genistein. The half-lives of plasma genistein and daidzein were
      8.36 and 5.79 h, respectively. The individual plasma and urinary concentrations
      of equol and O-DMA were quite variable; subjects were classified as high and low
      metabolizers. The high plasma concentration of isoflavones for at least several
      hours after a single ingestion of soy protein suggests that these compounds may
      interact with macromolecules and have biological effects.

PMID- 9772142
TI  - Feeding a low energy diet and refeeding a control diet affect glycolysis
      differently in the slow- and fast-twitch muscles of adult male Wistar rats.
AB  - Muscle glycogen concentrations in underfed (HYPO) and refed rats (RE) in an
      earlier study did not correlate with fatigue. We hypothesized that underfeeding
      slowed glycolysis in the slow-twitch soleus, but not in the fast-twitch extensor
      digitorum longus (EDL). Thirty adult male Wistar rats were randomly assigned to
      receive one of two isovolemic and micronutrient-complete liquid diets, a control
      (CN) energy-complete diet for 10 d or a diet 80% lower in energy (HYPO) for 7 d
      producing a 20% loss of initial weight. Rats were refed an energy-complete diet
      for 1 or 4 d (RE1, RE4). Rats were then anesthetized, and the soleus and EDL
      muscles of the hindlimbs were isolated and electrically stimulated in situ. The
      pre- and postfatigued muscles were freeze-clamped, lyophilized and stored at -70
      degreesC until assayed for specific glycolytic and Krebs cycle metabolites. The
      HYPO diet caused significantly slower glycolysis in the stimulated soleus but not
      the EDL compared with the CN diet as supported by the following: 1) a lower
      fructose-1,6-bisphosphate (F-1,6-P2)/fructose-6-phosphate (F-6-P) ratio; 2) a
      greater glucose-6-phosphate (G-6-P)/lactate ratio; 3) a lower lactate/glycogen
      ratio; and 4) lower lactate concentration. Four days of refeeding normalized the
      F-1,6-P2/F-6-P ratio, but did not improve the lactate/glycogen or the G-6
      P/lactate ratios. We conclude that undernutrition compromises glycolysis only in
      slow-twitch muscles and that 4 d of refeeding restores phosphofructokinase
      activity.

PMID- 9772143
TI  - The water-soluble extract of chicory influences serum and liver lipid
      concentrations, cecal short-chain fatty acid concentrations and fecal lipid
      excretion in rats.
AB  - Sprague-Dawley rats (n = 32) were fed diets without fiber (control) or containing
      1 or 5% chicory extract or 5% inulin for 4 wk; 0.2% cholesterol was added to all
      diets. Rats fed chicory extract and inulin diets had significantly higher serum
      high density lipoprotein (HDL) cholesterol and generally lower low density
      lipoprotein (LDL) cholesterol concentrations, thus significantly greater ratios
      of HDL/LDL cholesterol compared with the controls (P < 0.05). The serum
      apolipoprotein B/apolipoprotein A-1 ratio was significantly lower in rats fed
      diets containing chicory extract or inulin than that in rats fed fiber-free
      diets, due to significant reductions in apolipoprotein B concentration (P <
      0.05). Greater liver lipid and triglyceride concentrations were observed in rats
      fed chicory extract or inulin diets compared with the controls (P < 0.05).
      However, liver phospholipid and cholesterol concentrations were not significantly
      different among groups (P > 0.05). Addition of 5% inulin to the diet resulted in
      greater cecal weight, whereas both 5% chicory extract and 5% inulin resulted in
      greater cecal propionic acid concentration compared with the controls (P < 0.05).
      Rats fed chicory extract and inulin had significantly greater fecal lipid,
      cholesterol and bile acid excretions than those fed fiber-free diets (P < 0.05).
      The results of this study suggest that the improved lipid metabolism observed in
      rats fed chicory extract (mainly inulin component) may be caused by an alteration
      in the absorption and/or synthesis of cholesterol, which might result from the
      changes in cecal fermentation, and by an increase in the fecal excretion of
      lipid, cholesterol and bile acid.

PMID- 9772144
TI  - Confirmation of the role of rapidly fermentable carbohydrates in the expression
      of swine dysentery in pigs after experimental infection.
AB  - Two experiments were conducted to test the hypothesis that soluble non-starch
      polysaccharides (NSP) and resistant starch (RS) cause swine dysentery (SD) in
      pigs experimentally infected with the spirochete Serpulina hyodysenteriae. In
      Experiment 1, a source of soluble NSP (guar gum; GG), insoluble NSP (oat chaff;
      OC), resistant starch (retrograde cornstarch; RS) or a combination of GG and RS
      (GG + RS) was added to a diet containing cooked white rice (R), soybean meal
      (SBM) and animal protein (meat and bone meal, bloodmeal, fishmeal). A diet
      containing only cooked white rice, SBM and the sources of animal protein (AP) was
      also fed. In Experiment 2, three rice-based diets containing different levels of
      RS were fed to pigs. In Experiment 1, the pH of digesta in the cecum, proximal
      colon and distal colon of pigs fed diets R-GG, R-RS and R-GG + RS was lower (P <
      0.001), and volatile fatty acid concentration higher (P < 0.001), than in pigs
      fed diets R-OC and R-AP. Pigs fed diets with RS and GG + RS had greater (P <
      0.05) concentrations of ATP in the large intestine than pigs fed other diets.
      There were no significant differences in any fermentation indices measured in
      Experiment 2. In Experiment 1, pigs fed diets R-GG, R-RS and R-GG + RS were
      colonized with S. hyodysenteriae after experimental infection. However, only pigs
      consuming diets R-GG (4 of 5) and R-GG + RS (5 of 5) showed clinical signs of SD.
      Spirochetes were isolated from the feces of all pigs fed diets containing RS in
      Experiment 2. However, and in contrast to Experiment 1, 80-100% of pigs infected
      with S. hyodysenteriae displayed clinical signs of SD. These data confirm the
      role of fermentable carbohydrate in the pathogenesis of SD.

PMID- 9772145
TI  - Oscars, Astronotus ocellatus, have a dietary requirement for vitamin C.
AB  - We found that vitamin C is an essential nutrient for an Amazonian ornamental
      fish, the oscar (Astronotus ocellatus). This was demonstrated by the absence of L
      gulonolactone oxidase activity, the enzyme responsible for the biosynthesis of
      vitamin C, in liver or kidney of oscars and by a feeding trial in which oscars
      without vitamin C dietary supplementation developed clinical deficiency signs.
      Fish weighing 29.2 +/- 1.9 g were divided into four groups, and each group was
      fed a casein-based semipurified diet containing 0, 25, 75 or 200 mg ascorbic acid
      equivalent (AA)/kg diet for 26 wk. Vitamin C was supplemented in the diets as L
      ascorbyl-2-polyphosphate, a mixture of phosphate esters of ascorbate, which is
      more stable to oxidation than AA. At the end of 26 wk, fish fed no AA had
      significantly lower weight gain than fish fed the AA-supplemented diets (P <
      0.05). Oscars without dietary AA supplementation gained only 37% of their initial
      weight, compared with 112, 102 and 91% gained by fish fed 25, 75 and 200 mg AA/kg
      diet, respectively. After 25 wk without dietary supplementation of AA, fish began
      to develop clinical deficiency signs, including deformed opercula and jaws,
      hemorrhage in the eyes and fins, and lordosis. Histology indicated that fish
      without AA supplementation had deformed gill filament support cartilage and
      atrophied muscle fibers. Collagen content of the vertebral column was
      significantly lower in fish devoid of dietary AA (P < 0.05). Liver AA
      concentration varied in proportion to dietary concentration of AA. The minimum
      dietary AA concentration tested in this study, 25 mg AA/kg diet, was sufficient
      to prevent growth reduction and AA deficiency signs in oscars.

PMID- 9772146
TI  - Threonine requirement of neonatal piglets receiving total parenteral nutrition is
      considerably lower than that of piglets receiving an identical diet
      intragastrically.
AB  - Evidence is accumulating that the amino acid requirements for neonates receiving
      total parenteral nutrition (TPN) are significantly different than those for oral
      feeding and need to be determined. The parenteral threonine requirement was
      determined in 3-d-old male Yorkshire piglets (n = 25) by examining the effect of
      varying dietary threonine intakes [0.05-0.6 g/(kg.d)] on phenylalanine oxidation.
      The diet included adequate energy, total amino acids and phenylalanine, with
      excess tyrosine. Phenylalanine kinetics were determined from a primed, continuous
      intravenous infusion of L-[1-14C]phenylalanine. Phenylalanine oxidation,
      estimated from the rate of 14CO2 released in expired air during isotope infusion,
      decreased (P < 0.05) as threonine intake increased from 0.05 to 0.15 g/(kg.d) and
      was low and constant for threonine intakes >0.15 g/(kg.d). Using breakpoint
      analysis with 95% confidence interval (CI), mean requirement and safe level of
      parenteral threonine intake were estimated to be 0.19 and 0.21 g/(kg. d),
      respectively (equivalent to 13 and 14 mg/g amino acids, respectively). To compare
      these data with those of orally fed controls, we then repeated the experiment by
      infusing identical diets intragastrically to piglets (n = 25); the varying
      dietary threonine intakes were 0.1-1.2 g/(kg.d). Employing identical kinetics and
      analyses, the mean requirement and safe level of oral threonine intake were
      estimated to be 0.42 and 0.51 g/(kg.d), respectively (equivalent to 28 and 34
      mg/g amino acids, respectively). These data demonstrate that the threonine
      requirement of neonates during TPN is approximately 45% of the mean oral
      requirement.

PMID- 9772147
TI  - Lipopolysaccharide-induced reductions in food intake do not decrease the
      efficiency of lysine and threonine utilization for protein accretion in chickens.
AB  - Exposure of animals to infectious agents induces immune responses that result in
      reductions in food consumption and weight gain. The effect of these changes on
      amino acid requirements and utilization remains unclear. Three assays were
      conducted with young chicks with Escherichia coli lipopolysaccharide (LPS) used
      to stimulate the immune system. An initial study was conducted to evaluate the
      effects of LPS on animal performance. In a daily or alternate day injection
      regimen for 9 d, chicks were given intraperitoneal injections of sterile saline
      containing 0, 100 or 400 microgram LPS. Administration of 100 or 400 microgram
      LPS daily, or every other day, decreased both weight gain and food consumption.
      In two subsequent growth assays, chicks were fed graded levels of lysine or
      threonine and injected with either 0 or 400 microgram LPS every other day to
      evaluate the effect of LPS administration on the efficiency of amino acid
      utilization. At the three lowest amino acid doses, whole-body protein accretion
      was a linear function of supplemental lysine or threonine intake, and slopes of
      the accretion curves were not altered by LPS administration. The dietary lysine
      concentration required to maximize protein accretion was unaffected by LPS, but
      the absolute lysine intake required to maximize chick performance was lower in
      LPS-injected chicks than in saline-injected chicks. These results show that LPS
      administration reduces weight gain, food intake, efficiency of food utilization
      and the absolute quantity of lysine required to maximize these criteria. However,
      LPS administration does not affect the efficiency of amino acid utilization, nor
      does it affect the concentration of dietary lysine required to maximize
      performance.

PMID- 9772148
TI  - Plasma retinol is a major determinant of vitamin A utilization in rats.
AB  - We studied relationships among vitamin A intake, liver levels of vitamin A,
      plasma retinol concentrations and the irreversible utilization of vitamin A. To
      supplement existing data, we first used model-based compartmental analysis to
      determine vitamin A utilization and other kinetic parameters in male Sprague
      Dawley rats that had adequate liver vitamin A stores ( approximately 9000 nmol)
      and were fed a diet containing low levels of vitamin A. Plasma retinol kinetics
      were monitored for 43 d after administration of [3H]retinol-labeled plasma to
      rats consuming approximately 23 (Group 1, n = 6) or approximately 4.2 (Group 2, n
      = 6) nmol vitamin A/d. Data for plasma tracer vs. time and for tracer lost
      irreversibly by the end of the experiment, were fit to a three-compartment model
      in which plasma retinol exchanges with vitamin A in two kinetically distinct
      extravascular compartments. Irreversible utilization rates ( approximately 41
      nmol/d) were similar to those for rats that are in vitamin A balance, suggesting
      that, when liver vitamin A stores are adequate, utilization rate is not decreased
      to compensate for a low vitamin A intake. Multiple linear regression analysis was
      then used to relate these and previously collected data (total, 62 rats) on
      vitamin A intake (4. 2-49 nmol/d), plasma retinol concentration (1.4-2.5
      micromol/L) and liver vitamin A level (1.2-11,000 nmol) to vitamin A utilization
      (disposal rate, 4.2-68 nmol/d). A significant relationship (R2(adj) = 0.93) was
      found for the equation [disposal rate (nmol/d) = -0.720 (nmol/d) + 0.844 (d
      1).(plasma retinol; nmol) + 0.00139 (d-1).(liver vitamin A; nmol) +
      0.220.(vitamin A intake; nmol/d)]. Plasma retinol accounted for 92% of the
      variability in disposal rate (vs. 5% for liver vitamin A and 3% for vitamin A
      intake). We conclude that plasma retinol is a main determinant of the
      irreversible utilization of vitamin A in rats with low to moderate vitamin A
      intake.

PMID- 9772149
TI  - The marginal efficiency of utilization of all ileal digestible indispensable
      amino acids for protein gain is lower than 30% in preruminant calves between 80
      and 240 kg live weight.
AB  - A previous study showed that the marginal efficiency of utilization of digestible
      nitrogen for deposition in the body in preruminant calves is only approximately
      30%. The study consisted of two similar experiments that were performed in two
      live weight ranges: 80-160 and 160-240 kg. In each experiment, 36 calves were
      allotted to one of twelve dietary treatments, consisting of six protein intake
      levels at each of two protein-free energy intake levels. This paper presents
      amino acid analyses of dietary and body proteins of these experiments with the
      following goals: 1) to identify possible limiting indispensable amino acids, and
      2) to quantify the effect of protein and energy intake on the amino acid
      composition of deposited body proteins. The marginal efficiency of utilization of
      ileal digestible amino acids for deposition in the body did not exceed 30% for
      any of the indispensable amino acids. Increasing protein intake increased the
      ratio of indispensable to dispensable amino acids in deposited body proteins,
      likely caused by an increase in muscle-to-bone ratio in the carcass with a
      concomitant decrease in the proportion of collagen protein. It was concluded that
      the low marginal efficiency of utilization of digestible milk proteins for growth
      in preruminant calves of this weight range was not caused primarily by a severe
      limitation of a single indispensable amino acid in the diet.

PMID- 9772150
TI  - Fermentable dietary fiber increases GLP-1 secretion and improves glucose
      homeostasis despite increased intestinal glucose transport capacity in healthy
      dogs.
AB  - Ileal proglucagon gene expression and postprandial plasma concentrations of
      proglucagon-derived peptides are reported to change with the type and quantity of
      dietary fiber ingested by rats. Within the intestine, proglucagon encodes several
      proglucagon-derived peptides known to modulate intestinal absorption capacity and
      pancreatic insulin secretion. To determine whether the chronic ingestion of
      fermentable dietary fiber regulates the expression and synthesis of proglucagon
      derived peptides in the distal intestine to modulate glucose homeostasis, the
      following study was conducted: 16 adult dogs (23 +/- 2 kg) were fed isoenergetic,
      isonitrogenous diets containing a mixture of high fermentable dietary fibers
      (HFF) or low fermentable (LFF) wood cellulose for 14 d in a randomized cross-over
      design. Food was withheld for 16 h before an oral glucose tolerance test was
      conducted supplying 2 g of glucose/kg body wt, and peripheral blood was collected
      via a hind-leg catheter at 0, 15, 30, 45, 60, 90 and 120 min for plasma glucose,
      insulin and glucagon-like peptide-1(7-36)NH2 (GLP-1) analyses. Intestinal samples
      were collected after the second dietary treatment. Ileal proglucagon mRNA,
      intestinal (GLP-1) concentrations and the integrated area under the curves (AUC)
      for plasma GLP-1 and insulin were greater and plasma glucose AUC was reduced when
      dogs were fed the HFF diet compared to the LFF diet (P < 0.05). Intestinal villi
      heights, brush border and basolateral glucose transporter protein abundance and
      jejunal transport capacities were significantly greater when dogs were fed the
      HFF diet than when fed the LFF diet. In conclusion, improvements in glucose
      homeostasis are observed in healthy dogs when they ingest fermentable fibers.

PMID- 9772151
TI  - Physiologic concentrations of zinc affect the kinetics of copper uptake and
      transport in the human intestinal cell model, Caco-2.
AB  - Copper uptake was enhanced and copper transport was reduced in Caco-2 cells
      cultured in media containing high concentrations of zinc. Here we show that
      physiologic zinc concentrations also affect copper movement into and out of Caco
      2 cells. Cells were seeded onto Falcon membranes with high pore density and
      maintained in Dulbecco's modified Eagle's medium supplemented with 10% fetal
      bovine serum, nonessential amino acids, glucose and glutamine. In one experiment,
      the cells were exposed to media containing either 5 or 25 micromol zinc/L from d
      14 to 21 after seeding. Then, copper uptake and transport, in both apical and
      basolateral directions, were measured by using 64Cu. Cells exposed to 25 micromol
      zinc/L had a 25% higher (P < 0.05) uptake of 64Cu from the apical side than those
      exposed to 5 micromol zinc/L. There was no effect of zinc on 64Cu uptake from the
      basolateral side, even though the amount of label taken up was as much as
      threefold higher (P > 0.05) than from the apical side. Transport of 64Cu across
      the cell layer in both directions was 50% less (P < 0.05) in cells exposed to 25
      micromol zinc/L vs. 5 micromol zinc/L. In another experiment, zinc-exposed cells
      were labeled with 64Cu and efflux of the label to the apical and basolateral
      sides was measured over time. The rate of efflux to the apical side was linear
      and not affected by zinc. However, there was a 37% reduction (P < 0.05) in 64Cu
      efflux to the basolateral side by the higher zinc concentration. Curve-fit
      analysis showed that the basolateral efflux was made up of an exponential and a
      linear component. Cellular zinc concentrations were proportional to the zinc
      concentrations in the media. Although the data suggest that high media zinc
      inhibited the copper efflux transporter and enhanced the influx transporter,
      copper did not accumulate in the cell.

PMID- 9772152
TI  - Dietary lutein absorption from marigold extract is rapid in BALB/c mice.
AB  - Even though lutein can stimulate immunity and decrease cancer growth, no
      systematic studies are available on the uptake of lutein in mice. We studied the
      uptake of lutein in 8-wk-old female BALB/c mice fed a diet containing 0, 0.05,
      0.1, 0.2 or 0.4% lutein. Mice were killed on d 0, 3, 7, 14, 21 and 28 (n =
      6/period), and blood, spleen and liver were collected. Food intake and body,
      liver and spleen weights did not differ among treatment groups. Lutein +
      zeaxanthin were not detectable in the plasma, liver and spleen of unsupplemented
      mice. Mice fed lutein showed very rapid lutein + zeaxanthin absorption. On d 3,
      concentrations of plasma lutein + zeaxanthin had rapidly increased (P < 0.05) in
      lutein-fed mice and no further increases were observed. Plasma lutein +
      zeaxanthin concentrations did not differ among lutein-fed mice by d 7 (2.58 +/-
      0.2 micromol/L). Even though maximal uptake of plasma lutein + zeaxanthin was
      observed by d 3, uptake of lutein + zeaxanthin by the liver and especially by the
      spleen generally continued to increase (P < 0.05) through d 28 to reach
      concentrations of 0.11 +/- 0.001 (spleen) and 0.71 +/- 0. 0002 (liver) nmol/g.
      Therefore, dietary lutein is readily absorbed into the plasma and taken up by
      liver and spleen of mice. Plasma lutein + zeaxanthin concentrations were higher
      than in human studies; however, mice were fed lutein at a level several
      hundredfold greater than in humans. The liver is a major storage organ for lutein
      + zeaxanthin in mice. Uptake of lutein + zeaxanthin by the spleen suggests a role
      for lutein in modulating immunity.

PMID- 9772153
TI  - A high sucrose diet decreases the mechanical strength of bones in growing rats.
AB  - High sucrose diets alter mineral metabolism in humans and animals. We examined
      the effect of a high sucrose diet on bone growth, composition and mechanical
      strength in growing rats. Weanling Wistar rats received a high sucrose (43 g/100
      g) diet (9 males, 11 females). In the control diet (8 males, 8 females), sucrose
      was replaced with potato starch, providing an equal energy value. At the onset of
      the experiment, bones were marked by tetracycline. After 5 wk, the tibias and
      femurs were weighed, and maximum breaking strengths were determined. Tibias were
      cut at the tibia-fibular junction; the widths of the bone at the start of the
      experiment, the periosteal bone formation during the experiment, the widths of
      the medullary cavity and the final bone width were determined from tetracycline
      lines. Bone ash weight, Ca and P contents were determined. The breaking strengths
      of both bones were significantly lower in the sucrose-fed groups of both sexes.
      In females, the weight of both bones and the final width of the tibias were
      significantly lower in the sucrose-fed group. The Ca concentration in both bones
      and the P concentration in tibias were significantly lower in the sucrose-fed
      group. It was concluded that the metabolic interference induced by sucrose was
      the reason for the differences. The alterations were more pronounced in females,
      but independent of body weight.

PMID- 9772154
TI  - Dietary xylitol protects against weakening of bone biomechanical properties in
      ovariectomized rats.
AB  - The effects of dietary xylitol (xyl) on bone biomechanical properties in
      ovariectomized rats (ovx) were studied. Forty-two 3-mo-old female Wistar rats
      were divided into three groups of 14. Rats in two groups were ovariectomized,
      while those in the control group underwent a sham operation. All rats received a
      basal diet, and half of the ovx were given an additional 10 g/100 g dietary xyl
      supplementation. Three months later the rats were killed and their tibias, femurs
      and humeri were prepared. The tibias were used for analyses of bone density and
      trabecular bone volume (BV/TV) and for the three-point bending test. The femurs
      were used for the torsion test and for the loading test of the femoral neck. The
      humeri were used for analyses of bone ash weight and bone concentrations of
      calcium and phosphorus. Dietary xyl gave a significant protection against
      ovariectomy-caused decline of tibial stress in the three-point bending test, of
      femoral shear stress in the torsion test, and of stress of the femoral neck,
      without affecting bone elasticity values. Xyl restricted the ovariectomy-caused
      reduction in bone density, in bone ash weight and in concentrations of bone
      calcium and phosphorus. Furthermore, trabecular bone loss in ovx was
      significantly suppressed by dietary xyl. These results indicate that a 10%
      dietary supplementation of xyl in ovx has a protective effect against the
      weakening of bone biomechanical properties. This is related to greater BV/TV and
      maintained bone mineral content.

PMID- 9772155
TI  - True calcium absorption in the intestine is enhanced by fructooligosaccharide
      feeding in rats.
AB  - Fructooligosaccharides (FOS) have been shown to stimulate apparent calcium
      absorption in the intestine. In this study, we examined the effect of FOS on true
      calcium absorption using the calcium balance in combination with the 45Ca
      kinetics method. Sixteen 45-d-old male Wistar rats were randomly divided into two
      groups, a control group (n = 8) and a FOS group (n = 8). The diet fed to the FOS
      group contained 5% FOS, at the expense of half of the sucrose in the control
      diet. After an adaptation period (3 d) and a free-access period (3 d) that were
      used to estimate the amount of food required for pair-feeding on the basis of
      calcium, all of the rats were pair-fed throughout the experiment from the age of
      51 d. A constant amount of calcium was fed to the rats in each group (95 mg /d).
      At age 60 d, a 3-d metabolic study was started by the intravenous injection of
      45Ca. Several variables were calculated on the bases of measurements of calcium
      intake, calcium in feces and serum, and 45Ca in feces, urine and serum. Both true
      and apparent calcium absorption in the intestine (Vad and Vna) and urinary
      calcium were significantly greater in rats that had been fed FOS. There were no
      differences between the groups in endogenous net calcium excretion into feces
      (Vf; Vad - Vna). The calcium balance was also enhanced by FOS. Calcium balance in
      the FOS group was significantly correlated with the absorbed calcium (r2 = 0.936,
      P < 0.01), as was that in the control group (r2 = 0.994, P < 0.01). These results
      suggest that the increased true calcium absorption and balance produced by FOS
      feeding might improve bone calcification.

PMID- 9772156
TI  - Reduced glucose consumption in the curly tail mouse does not initiate the
      pathogenesis leading to spinal neural tube defects.
AB  - At embryonic stages of neural tube closure, the mouse embryo exhibits a high rate
      of glycolysis with glucose as the main energy source. In the curly tail mouse,
      often used as model system for study of human neural tube defects, a delay in
      closure of the posterior neuropore (PNP) is proposed to be indirectly caused by a
      proliferation defect in the caudal region. Because glucose is important for
      proliferation, we tested glucose uptake in curly tail and control embryos, and in
      a BALB/c-curly tail recombinant strain. The structure and expression of Glut-1, a
      glucose transporter molecule that is abundantly present during those embryonic
      stages and that has been mapped in the region of the major curly tail gene, were
      also studied; however, no strain differences could be demonstrated. Glucose
      uptake was determined by measuring glucose depletion from the medium in long-term
      embryo cultures that encompassed the stages of PNP closure and by measuring
      accumulation of 3H-deoxyglucose in short-term cultures at the stages of early and
      final PNP closure. Both approaches indicated a reduced glucose uptake by curly
      tail and recombinant embryos. Surprisingly, the uptake per cell appeared normal,
      accompanied by a significantly lower DNA content of the mutant embryos.
      Therefore, it is unlikely that reduced cell proliferation is caused by a
      reduction in glucose supply during the pathogenesis of the defects in curly tail
      embryos. The reduced DNA content as well as the reduced glucose uptake per embryo
      are likely downstream effects of the aberrant proliferation pattern.

PMID- 9772158
TI  - Dietary guidelines for children: where are we heading?

PMID- 9772157
TI  - Dietary excess of vitamin B-6 affects the concentrations of amino acids in the
      caudate nucleus and serum and the binding properties of serotonin receptors in
      the brain cortex of rats.
AB  - Vitamin B-6 is a cofactor in many reactions of nitrogen metabolism. Deficiency
      alters tissue amino acid concentrations but effects of excess vitamin B-6 have
      not been well described. We fed female rats (218 g, 7 per group) 1 (control), 10,
      100, 175 or 250x) the National Research Council recommended level of pyridoxine
      HCl (7 mg/kg) for 10 wk and measured serum amino acids, amino acids and
      neurotransmitters in brain regions and the binding properties of serotonin
      receptors in the cerebral cortex using a ketanserin binding assay. Rats were
      decapitated, and unheparinized blood was obtained. In the caudate nucleus,
      concentrations of glutamate, threonine, taurine, methionine, gamma-amino-butyric
      acid and the sum of the essential amino acids in groups 10X and 100X were
      approximately 130 to 180% of control levels (P < 0.05); groups 1X, 175X and 250X
      were not different. A similar pattern was seen in the serum for serine, glycine,
      aspartate and ornithine; the latter two amino acids increased to over 200% of
      control in group 100X. In the ketanserin binding assay, both the antagonist
      binding affinity and the maximal number of binding sites were higher for group
      100X than for 1X, 175X and 250X, and were higher for 10X than for 1X.
      Norepinephrine in the raphe nucleus followed a similar biphasic pattern. Excess
      dietary pyridoxine affected brain and serum concentrations of some amino acids
      and binding properties of cortical serotonin receptors in a biphasic pattern over
      the range of concentrations fed in this study.

PMID- 9772159
TI  - The murine anti-human common gamma chain monoclonal antibody CP.B8 blocks the
      second step in the formation of the intermediate affinity IL-2 receptor.
AB  - A murine monoclonal antibody, CP.B8, specific for the extracellular portion of
      the human common gamma (gammac) chain, and its Fab fragment are shown to block
      the binding of IL-2 to COS-7 cells transfected with the cDNA for the full-length
      IL-2 receptor beta (IL-2Rbeta) and gammac chains, components which together
      comprise the intermediate affinity IL-2 receptor (IL-2R) expressed on the surface
      of resting T cells, NK cells, and on certain intestinal epithelial cells. To
      investigate the mechanism of this inhibition, the extracellular portions of the
      IL-2Rbeta and gammac chains were expressed and purified, and their interactions
      with each other and with IL-2 were studied by gel filtration and by surface
      plasmon resonance (SPR). By gel filtration, a stable ternary complex was formed
      by association of the three proteins, while no stable binary complexes were
      detected between any two of the three proteins. By SPR analysis, IL-2 was shown
      to associate rapidly with IL-2Rbeta, forming a binary complex with an equilibrium
      dissociation constant (Kd) of 800 nM, which permitted subsequent association of
      the gammac chain. Dissociation of the IL-2/IL-2Rbeta/gammac chain complex was
      significantly slower than dissociation of the IL-2/IL-2Rbeta complex. Using these
      model systems, we tested the ability of mAb CP.B8 to inhibit the association of
      the gammac chain with IL-2 and IL-2Rbeta. By gel filtration, mAb CP.B8 formed a
      stable complex with the gammac chain, preventing its association with IL-2 and IL
      2Rbeta. MAb CP.B8 was also capable of dissociating the gammac chain already
      complexed with IL-2 and IL-2Rbeta. SPR analysis confirmed these findings and
      showed, in addition, that the Fab fragment of CP.B8 was also capable of
      inhibiting the association of the gammac chain with the IL-2/IL-2Rbeta complex.
      We conclude that mAb CP.B8 blocks the second step in the formation of the
      intermediate affinity IL-2R on the surface of transfected COS-7 cells by binding
      at or close to a region on the gammac chain that is involved in contact with IL-2
      and/or IL-2Rbeta.

PMID- 9772160
TI  - Evolution of enzymatic activities in the enolase superfamily: partitioning of
      reactive intermediates by (D)-glucarate dehydratase from Pseudomonas putida.
AB  - Glucarate dehydratase (GlucD) from Pseudomonas putida catalyzes the dehydration
      of both (D)-glucarate and (L)-idarate to 3-deoxy-(L)-threo-2-hexulosarate as well
      as their epimerization. (D)-[6-13C]Glucarate and (L)-[6-13C]idarate have been
      synthesized for use in continuous assay of the reactions catalyzed by GlucD by
      both 13C and 1H NMR spectroscopies, thereby allowing the simultaneous measure of
      both the dehydration and epimerization reactions. Substrate and solvent isotope
      effects for the dehydration reactions have been quantitated. The mechanism of the
      GlucD-catalyzed reaction is discussed in the context of that previously
      established for the homologous mandelate racemase from P. putida, also a member
      of the enolase superfamily whose members catalyze reactions initiated by
      abstraction of a proton alpha to a carboxylate group.

PMID- 9772161
TI  - Evolution of enzymatic activities in the enolase superfamily: crystal structure
      of (D)-glucarate dehydratase from Pseudomonas putida.
AB  - The structure of (D)-glucarate dehydratase from Pseudomonas putida (GlucD) has
      been solved at 2.3 A resolution by multiple isomorphous replacement and refined
      to a final R-factor of 19.0%. The protein crystallizes in the space group I222
      with one subunit in the asymmetric unit. The unit cell dimensions are a = 69.6 A,
      b = 108.8 A, and c = 122.6 A. The crystals were grown using the batch method
      where the primary precipitant was poly(ethylene glycol) 1000. The structure
      reveals that GlucD is a tetramer of four identical polypeptides, each containing
      451 residues. The structure was determined without a bound substrate or substrate
      analogue. Three disordered regions are noted: the N-terminus through residue 11,
      a loop containing residues 99 through 110, and the C-terminus from residue 423.
      On the basis of primary sequence alignments, we previously concluded that GlucD
      is a member of the mandelate racemase (MR) subfamily of the enolase superfamily
      [Babbitt, P. C., Hasson, M. S., Wedekind, J. E., Palmer, D. R. J., Barrett, W.
      C., Reed, G. J., Rayment, I., Ringe, D., Kenyon, G. L., and Gerlt, J. A. (1996)
      Biochemistry 35, 16489-16501]. This prediction is now verified, since the overall
      fold of GlucD is strikingly similar to those of MR, muconate lactonizing enzyme
      I, and enolase. Also, many of the active site residues of GlucD can be
      superimposed on those found in the active site of MR. The implications of this
      structure on the evolution of catalysis in the enolase superfamily are discussed.

PMID- 9772162
TI  - Evolution of enzymatic activities in the enolase superfamily: characterization of
      the (D)-glucarate/galactarate catabolic pathway in Escherichia coli.
AB  - The genes encoding the enzymes in the (D)-glucarate/galactarate catabolic pathway
      have been identified in the Escherichia coli genome. These encode, in three
      transcriptional units, (D)-glucarate dehydratase (GlucD), galactarate
      dehydratase, 5-keto-4-deoxy-(D)-glucarate aldolase, tartronate semialdehyde
      reductase, a glycerate kinase that generates 2-phosphoglycerate as product, and
      two hexaric acid transporters. We also have identified a gene proximal to that
      encoding GlucD that encodes a protein that is 72% identical in primary sequence
      to GlucD (GlucD-related protein or GlucDRP). However, whereas GlucD catalyzes the
      efficient dehydration of both (D)-glucarate and (L)-idarate as well as their
      epimerization, GlucDRP is significantly impaired in both reactions. Perhaps
      GlucDRP is an example of gene duplication and evolution in progress in the E.
      coli chromosome.

PMID- 9772163
TI  - Crystal structures of the G protein Gi alpha 1 complexed with GDP and Mg2+: a
      crystallographic titration experiment.
AB  - The effect of Mg2+ binding on the conformation of the inactive GDP-bound complex
      of the heterotrimeric G protein alpha subunit Gi alpha 1 has been investigated by
      X-ray crystallography. Crystal structures of the Gi alpha 1.GDP complex were
      determined after titration with 5, 10, 100, and 200 mM Mg2+. Comparison of these
      structures with that of the Mg2+-free complex revealed Mg2+ bound at the same
      site as observed in the structure of the active, Gi alpha 1. GTP gamma S.Mg2+
      bound complex of Gi alpha 1, with a similar coordination scheme except for the
      substitution of a water molecule for an oxygen ligand of the gamma-phosphate of
      Gi alpha 1.GTP gamma S. Mg2+. In contrast to the GDP.Mg2+ complex of Gt alpha and
      of other G proteins, switch I residues of Gi alpha 1 participate in Mg2+ binding
      and undergo conformational changes as a consequence of Mg2+ binding. Partial
      order is induced in switch II, which is disordered in the Mg2+-free complex, but
      no order is observed in the switch III region. This contrasts with the GDP.Mg2+
      complex of Gt alpha in which both switch II and III switch are ordered. Mg2+
      binding also induces binding of an SO42- molecule to the active site in a manner
      which may mimic a Gi alpha 1.GDP.PO42-.Mg2+ product complex. Implications of
      these findings are discussed.

PMID- 9772164
TI  - Stabilization of radical intermediates by an active-site tyrosine residue in
      methylmalonyl-CoA mutase.
AB  - The adenosylcobalamin-dependent methylmalonyl-CoA mutase catalyzes the reversible
      rearrangement of methylmalonyl-CoA into succinyl-CoA by a free-radical mechanism.
      The recently solved X-ray crystal structure of methylmalonyl-CoA mutase from
      Propionibacterium shermanii has shown that tyrosine 89 is an active-site residue
      involved in substrate binding. The role of tyrosine 89, a conserved residue among
      methylmalonyl-CoA mutases, has been investigated by using site-directed
      mutagenesis to replace this residue with phenylalanine. The crystal structure of
      the Tyr89Phe mutant was determined to 2.2 A resolution and was found to be
      essentially superimposable on that of wild-type. Mutant and wild-type enzyme have
      very similar KM values, but kcat for the Tyr89Phe mutant is 580-fold lower than
      for wild-type. The rate of release of tritium from 5'-[3H]adenosylcobalamin
      during the enzymatic reaction and its rate of appearance in substrate and product
      were measured. The tritium released was found to partition unequally between
      methylmalonyl-CoA and succinyl-CoA, in a ratio of 40:60 when the reaction was
      initiated by addition of methylmalonyl-CoA and in a ratio of 10:90 when the
      reaction was initiated by addition of succinyl-CoA. The overall release of
      tritium was four times faster when succinyl-CoA was used as substrate. The
      tritium isotope effect on the enzyme catalyzed hydrogen transfer, measured with
      methylmalonyl-CoA as a substrate, was kH/kT = 30, which is within the expected
      range for a full primary kinetic tritium isotope effect. The different
      partitioning of tritium, dependent upon which substrate was used, and the normal
      value for the kinetic tritium isotope effect contrast markedly with the behavior
      of wild-type mutase. It appears that the loss of a single interaction involving
      the hydroxyl group of tyrosine 89 both affects the stability of radical
      intermediates and decreases the rate of interconversion of the substrate- and
      product-derived radicals.

PMID- 9772165
TI  - Crystal structures of HIV-1 reverse transcriptase in complex with carboxanilide
      derivatives.
AB  - The carboxanilides are nonnucleoside inhibitors (NNIs) of HIV-1 reverse
      transcriptase (RT), of potential clinical importance. The compounds differ in
      potency and in their retention of potency in the face of drug resistance
      mutations. Whereas UC-84, the prototype compound, only weakly inhibits many RTs
      bearing single point resistance mutations, inhibition by UC-781 is little
      affected. It has been proposed that UC-38 and UC-781 may form quaternary
      complexes with RT at a site other than the known binding pocket of other NNIs. X
      ray crystal structures of four HIV-1 RT-carboxanilide complexes (UC-10, UC-38, UC
      84, and UC-781) reported here reveal that all four inhibitors bind in the usual
      NNI site, forming binary 1:1 complexes with RT in the absence of substrates with
      the amide/thioamide bond in cis conformations. For all four complexes the anilide
      rings of the inhibitors overlap aromatic rings of many other NNIs bound to RT. In
      contrast, the second rings of UC-10, UC-84, and UC-781 do not bind in equivalent
      positions to those of other "two-ring" NNIs such as alpha-APA or HEPT
      derivatives. The binding modes most closely resemble that of the structurally
      dissimilar NNI, Cl-TIBO, with a common hydrogen bond between each carboxanilide
      NH- group and the main-chain carbonyl oxygen of Lys101. The binding modes differ
      slightly between the UC-10/UC-781 and UC-38/UC-84 pairs of compounds, apparently
      related to the shorter isopropylmethanoyl substituents of the anilide rings of UC
      38/UC-84, which draws these rings closer to residues Tyr181 and Tyr188. This in
      turn explains the differences in the effect of mutated residues on the binding of
      these compounds.

PMID- 9772166
TI  - Structural and kinetic evidence for strain in biological catalysis.
AB  - A classic hypothesis for enzyme catalysis is the induction of strain in the
      substrate. This notion was first expressed by Haldane with the lock and key
      analogy-"the key does not fit the lock perfectly but exercises a certain strain
      on it" (1). This mechanism has often been invoked to explain the catalytic
      efficiency of enzymes but has been difficult to establish conclusively (2-7).
      Here we describe X-ray crystallographic and mutational studies of an antibody
      metal chelatase which strongly support the notion that this antibody catalyzes
      metal ion insertion into the porphyrin ring by inducing strain. Analysis of the
      germline precursor suggests that this strain mechanism arose during the process
      of affinity maturation in response to a conformationally distorted N
      alkylmesoporphyrin.

PMID- 9772167
TI  - Functional requirements for specific ligand recognition by a biotin-binding RNA
      pseudoknot.
AB  - Ligand-binding RNAs and DNAs (aptamers) isolated by in vitro selection from
      random sequence pools provide convenient model systems for understanding the
      basic relationships between RNA structure and function. We describe a series of
      experiments that define the functional requirements for an RNA motif that
      specifies high-affinity binding to the carboxylation cofactor biotin. A simple
      pseudoknot containing an adenosine-rich loop accounts for binding in all
      independently derived aptamers selected to bind biotin, suggesting that it alone
      represents a global optimum for recognition of this particular nonaromatic,
      electrostatically neutral ligand. In contrast to virtually all previously
      identified aptamers, unpaired nucleotides make up a small fraction of the binding
      motif. Instead, the identity of 14 nucleotides involved in base pairing is highly
      conserved among functional clones and their substitution by nonidentical base
      pairs significantly reduces or eliminates binding. Chemical probing is consistent
      with the predicted pseudoknot motif and indicates that relatively little change
      in structure accompanies ligand binding, a strong contrast with results for other
      aptamers. Competition experiments suggest that the aptamer recognizes all parts
      of the biotin ligand, including its thiophane ring and fatty acid tail. Two
      alternative modes of binding are suggested by a three-dimensional model of the
      pseudoknot, both of which entail significant interactions with base-paired
      nucleotides.

PMID- 9772168
TI  - Bifunctional peptide boronate inhibitors of thrombin: crystallographic analysis
      of inhibition enhanced by linkage to an exosite 1 binding peptide.
AB  - The affinity of the hirudin49-64 segment for exosite 1 of thrombin has been used
      previously to enhance the potency of simple competitive inhibitors [DiMaio, J.,
      Gibbs, B., Munn, D., Lefebvre, J. , Ni, F., Konishi, Y. (1990) J. Biol. Chem.
      265, 21698-21703., and Maraganore, J. M., Bourdon, P., Jablonski, J.,
      Ramachandran, K. L., and Fenton, J. W., II (1990) Biochemistry 29, 7095-7087.].
      Using a similar approach, we have enhanced the activity of two active site
      directed thrombin inhibitors by attaching this segment via a novel reverse
      oriented linker to each of two tripeptide boronate inhibitors. At P1, compound 1
      contains an arginine-like, isothiouronium, side chain, while compound 2 contains
      an uncharged, bromopropyl residue. Inhibition of human alpha-thrombin by compound
      1 shows slow, tight-binding competitive kinetics (final Ki of 2.2 pM, k1 of 3.51
      x 10(7) M-1 s-1, and k-1 of 1.81 x 10(-)4 s-1). The addition of hirugen peptide
      (20 microM) competes for exosite 1 binding and restores the k1 and k-1 to that of
      the analogous tripeptide, 0.29 x 10(7) M-1 s-1 and 0.13 x 10(-)4 s-1,
      respectively. Compound 1 has enhanced specificity for thrombin over trypsin with
      KiTry/KiThr of approximately 900 compared to the analogous tripeptide, with
      KiTry/KiThr of approximately 4. Compound 2 acts as a competitive inhibitor (KiThr
      of 0.6 nM) and is highly selective with no effect on trypsin. Crystallographic
      analysis of complexes of human alpha-thrombin with compound 1 (1.8 A) and
      compound 2 (1.85 A) shows a covalent bond between the boron of the inhibitor and
      Ser195 (bond lengths B-O of 1.55 and 1.61 A, respectively). The isothiouronium
      group of compound 1 forms bidentate interactions with Asp189. The P2 and P3
      residues of the inhibitors form interactions with the S2 and S3 sites of thrombin
      similar to other D-Phe-Pro based inhibitors [Bode, W., Turk, D., and Karshikov,
      A. (1992) Protein Sci. 1, 426-471.]. The linker exits the active site cleft of
      thrombin forming no interactions, while the binding of Hir49-64 segment to
      exosite 1 is similar to that previously described for hirudin [Rydel, T. J.,
      Tulinsky, A., and Bode, W. (1991) J. Mol. Biol. 221, 583-601.]. Because of the
      similarity of binding at each of these sites to that of the analogous peptides
      added alone, this approach may be used to improve the inhibitory activity of all
      types of active site directed thrombin inhibitors and may also be applicable to
      the design of inhibitors of other proteases.

PMID- 9772169
TI  - Microsecond rotational dynamics of spin-labeled myosin regulatory light chain
      induced by relaxation and contraction of scallop muscle.
AB  - We have used saturation transfer electron paramagnetic resonance (ST-EPR) to
      study the rotational dynamics of spin-labeled regulatory light chain (RLC) in
      scallop (Placopecten magellanicus) muscle fibers. The single cysteine (Cys 51) in
      isolated clam (Mercenaria) RLC was labeled with an indanedione spin label
      (InVSL). RLC was completely and specifically extracted from scallop striated
      muscle fibers, eliminating the Ca sensitivity of ATPase activity and isometric
      force, which were both completely restored by stoichiometric incorporation of
      labeled RLC. The EPR spectrum of the isolated RLC revealed nanosecond rotational
      motions within the RLC, which were completely eliminated when the labeled RLC was
      bound to myosin heads in myofibrils or fibers in rigor. This is the most strongly
      immobilized RLC-bound probe reported to date and thus offers the most reliable
      detection of the overall rotational motion of the LC domain. Conventional EPR
      spectra of oriented fibers indicated essentially complete probe disorder,
      independent of ATP and Ca, eliminating orientational dependence and thus making
      this probe ideal for unambiguous measurement of microsecond rotational motions of
      the LC domain by ST-EPR. ST-EPR spectra of fibers in rigor indicated an effective
      rotational correlation time (taureff) of 140 +/- 5 microseconds, similar to that
      observed for the same spin label bound to the catalytic domain. Relaxation by ATP
      induced microsecond rotational motion (taureff = 70 +/- 4 microseconds), and this
      motion was slightly slower upon Ca activation of isometric contraction (taureff =
      100 +/- 5 microseconds). These motions in relaxation and contraction are similar
      to, but slower than, the motions previously reported for the same spin label
      bound to the catalytic domain. These results support a model for force generation
      involving rotational motion of the LC domain relative to the catalytic domain and
      dynamic disorder-to-order transitions in both domains.

PMID- 9772170
TI  - Specific requirements for cytochrome c-550 and the manganese-stabilizing protein
      in photoautotrophic strains of Synechocystis sp. PCC 6803 with mutations in the
      domain Gly-351 to Thr-436 of the chlorophyll-binding protein CP47.
AB  - The requirement of cytochrome c-550 (PSII-V) in photosystem II (PSII) has been
      assessed in Synechocystis sp. PCC 6803 containing mutations between Gly-351 and
      Thr-436 of the loop E domain of the chlorophyll a-binding protein CP47. Six
      photoautotrophic strains were utilized to compare the effect of removal of either
      the manganese-stabilizing protein (PSII-O) or PSII-V on PSII activity in vivo.
      These were a wild-type control; two strains with amino acid deletions, Delta(R384
      V392) and Delta(G429-T436); and three carrying specific amino acid substitutions,
      G351L/T365Q, G351L/E364Q/T365Q, and G351L/E353Q/E355Q/T365Q. The removal of PSII
      O prevented the assembly of PSII in Delta(G429-T436) but not in Delta(R384-V392).
      Neither Delta(G429-T436) nor Delta(R384-V392) could support photoautotrophic
      growth in the absence of PSII-V. In chloride-limiting conditions, the
      photoautotrophic growth of Delta(R384-V392) was severely impaired and that of
      Delta(G429-T436) totally inhibited, and no strains lacking PSII-V could grow in
      chloride-limiting or calcium-limiting media. Substitutions at Gly-351, Glu-353,
      Glu-355, and Thr-365 produced phenotypes that were similar to those of the
      control in the presence or absence of PSII-O and PSII-V, but removal of PSII-O
      from G351L/E364Q/T365Q produced a significant reduction of assembled PSII centers
      and an enhanced sensitivity to photoinactivation while removal of PSII-V
      prevented photoautotrophic growth. The additional mutants E364Q:DeltaPSII-V and
      E364G:DeltaPSII-V demonstrated that this inhibition was a consequence of the
      mutation at Glu-364. These results also show that the removal of PSII-V, in vivo,
      produces phenotypes in the CP47 mutants examined that are either similar or more
      severe than those resulting from the removal of PSII-O.

PMID- 9772171
TI  - Oxygenic photosystem II: the mutation D1-D61N in Synechocystis sp. PCC 6803
      retards S-state transitions without affecting electron transfer from YZ to P680+.
AB  - Photosynthetic oxygen evolution is powered by photosystem II (PSII), in
      particular by the oxidized chl a-aggregate P680+, and catalyzed by the oxygen
      evolving complex (Mn4X-entity) as well as a tyrosine residue (YZ). The role of
      particular amino acids as cofactors of electron and proton transfer or as
      modulators of the activity is still ill-defined. The effects of single-site
      mutations at the donor side of PSII on the partial reactions of water oxidation
      have been primarily studied in whole cells. Because of better signal-to-noise in
      oxygen-evolving core preparations more detailed information on the electronic,
      protonic, and electrostatic events is expected from studies with such material.
      We investigated cells and oxygen-evolving core preparations from the wildtype of
      Synechocystis sp. PCC 6803 and point-mutants of D1-D61. In cells, oxygen-release
      was slowed drastically in D61A (8-fold) and D61N (10-fold) compared to WT,
      whereas it remained unchanged in D61E within the time resolution of the
      measurements. In core preparations, the S1 --> S2 and S2 --> S3 transitions were
      slowed approximately 2-fold in D61N compared to WT. However, the nanosecond
      components of electron transfer from YZ to P680+ were unchanged in the same
      mutant. We conclude that substitution of a neutral residue for D1-D61 selectively
      affects electron-transfer events on the donor side of YZ.

PMID- 9772172
TI  - Proton uptake by carboxylic acid groups upon photoreduction of the secondary
      quinone (QB) in bacterial reaction centers from Rhodobacter sphaeroides: FTIR
      studies on the effects of replacing Glu H173.
AB  - In the photosynthetic reaction center (RC) from Rhodobacter sphaeroides, Glu
      H173, located approximately 7 A from the center of the secondary quinone acceptor
      QB, is expected to contribute to proton uptake upon QB- formation in response to
      the movement of an electron in its vicinity. Steady-state FTIR difference
      spectroscopy provides a method to monitor proton uptake by carboxylic acids upon
      photochemical changes. The FTIR spectra corresponding to the photoreduction of QB
      were obtained at pH 7 for RCs containing Glu (native), Gln (EQ H173), or Asp (ED
      H173) at the H173 site. No new bands were observed in the carboxylic acid region
      (1770-1700 cm-1) in any of the mutant RCs compared to native RCs. In addition,
      the positive band at 1728 cm-1, previously assigned to Glu L212 [Nabedryk, E.,
      Breton, J., Hienerwadel, R., Fogel, C., Mantele, W., Paddock, M. L., and Okamura,
      M. Y. (1995) Biochemistry 34, 14722-14732], remained present in all of the mutant
      RCs. This result shows that Glu H173 is not a major contributor to proton uptake
      upon QB- formation and further strengthens the assignment of the 1728 cm-1 band
      to Glu L212. An increase in the 1728 cm-1 band was observed in the EQ H173 RCs
      compared to that of either the ED H173 or native RCs. These changes are
      consistent with Glu and Asp at H173 remaining ionized in the QB and QB- states.
      Changes in the absorption regions of the semiquinone and amide or side chain
      groups in the spectra of the mutant RCs suggest slight changes in the protein
      structure compared to those of native RCs, which could contribute to the altered
      kinetics observed in the mutant RCs.

PMID- 9772173
TI  - Importance of specific native lipids in controlling the photocycle of
      bacteriorhodopsin.
AB  - Brief treatment of purple membrane (PM) with dilute detergent can cause major
      disruption of the BR photocycle without disrupting the trimer structure of BR
      [Mukhopadhyay et al. (1996) Biochemistry 35, 9245-9252]. Normal photocyle
      behavior can be recovered by incubating the damaged membranes with a total
      extract of the five types of native lipids present in PM. It is shown here that
      full restoration can also be obtained with combinations of squalene (SQ) and
      phosphatidyl glycerophosphate (PGP) which act synergistically. The addition of SQ
      to suboptimal levels of PGP induces complete reconstitution, principally by
      restoring the characteristics of the fast M intermediate, Mf (as defined in
      Mukhopadhyay et al. (1996) Biochemistry 35, 9245-9252). The addition of small
      amounts of PGP to SQ, which alone is ineffective, also induces full
      reconstituion. At very high levels, full reconstitution can be obtained with PGP
      alone. These results, in combination with earlier studies which implicate an
      acidic amino acid residue [Bose et al. (1997) J. Phys. Chem. B 101, 10584-10587],
      suggest that a crucial interaction between a particular amino acid residue and a
      SQ-PGP lipid complex may be essential for normal BR photocycle activity.

PMID- 9772174
TI  - The post-translational modification in cytochrome c oxidase is required to
      establish a functional environment of the catalytic site.
AB  - Mutation of tyrosine-288 to a phenylalanine in cytochrome c oxidase from
      Rhodobacter sphaeroides drastically alters its properties. Tyr-288 lies in the
      CuB-cytochrome a3 binuclear catalytic site and forms a hydrogen bond with the
      hydroxy group on the farnesyl side chain of the heme. In addition, through a post
      translational modification, Y288 is covalently linked to one of the histidine
      ligands that is coordinated to CuB. In the Y288F mutant enzyme, the "as-isolated"
      preparation is a mixture of reduced cytochrome a and oxidized cytochrome a3. The
      cytochrome a3 heme, which is largely six-coordinate low-spin in both oxidation
      states of the mutant, cannot be reduced by cytochrome c, but only by dithionite,
      possibly due to a large decrease in its reduction potential. It is postulated
      that the Y288F mutation prevents the post-translational modification from
      occurring. As a consequence, the catalytic site becomes disrupted. Thus, one role
      of the post-translational modification is to stabilize the functional catalytic
      site by maintaining the correct ligands on CuB, thereby preventing nonfunctional
      ligands from coordinating to the heme.

PMID- 9772176
TI  - Guanidine-induced denaturation of beta-glycosidase from Sulfolobus solfataricus
      expressed in Escherichia coli.
AB  - Guanidine-induced denaturation of Sulfolobus solfataricus beta-glycosidase
      expressed in Escherichia coli, Sbetagly, was investigated at pH 6.5 and 25
      degreesC by means of circular dichroism and fluorescence measurements. The
      process proved reversible when the protein concentration was lower than 0.01 mg
      mL-1. Moreover, the transition curves determined by fluorescence did not coincide
      with those determined by circular dichroism, and the GuHCl concentration
      corresponding at half-completion of the transition increased on raising the
      protein concentration in the range 0.001-0.1 mg mL-1. Gel filtration
      chromatography experiments showed that, in the range 2-4 M GuHCl, there was an
      equilibrium among tetrameric, dimeric, and monomeric species. These findings,
      unequivocally, indicated that the guanidine-induced denaturation of Sbetagly was
      not a two-state transition with concomitant unfolding and dissociation of the
      four subunits. A mechanism involving a dimeric intermediate species was proposed
      and was able to fit the experimental fluorescence intensity transition profiles,
      allowing the estimation of the total denaturation Gibbs energy change at 25
      degreesC and pH 6.5. This figure, when normalized for the number of residues,
      showed that, at room temperature, Sbetagly has a stability similar to that of
      mesophilic proteins.

PMID- 9772175
TI  - SecB binds only to a late native-like intermediate in the folding pathway of
      barstar and not to the unfolded state.
AB  - SecB is a cytosolic, tetrameric chaperone of Escherichia coli which maintains
      precursor proteins in a translocation competent state. We have investigated the
      effect of SecB on the refolding kinetics of the small protein barstar in 1 M
      guanidine hydrochloride at pH 7.0 and 25 degreesC using fluorescence
      spectroscopy. We show that SecB does not bind either the native or the unfolded
      states of barstar but binds to a late near-native intermediate along the folding
      pathway. For barstar, polypeptide collapse and formation of a hydrophobic surface
      are required for binding to SecB. SecB does not change the apparent rate constant
      of barstar refolding. The kinetic data for SecB binding to barstar are not
      consistent with simple kinetic partitioning models.

PMID- 9772177
TI  - Redox-dependent acetyl transfer partial reaction of the acetyl-CoA
      decarbonylase/synthase complex: kinetics and mechanism.
AB  - Acetyl-CoA decarbonylase/synthase (ACDS) is a multienzyme complex that plays a
      central role in energy metabolism in Methanosarcina barkeri grown on acetate. The
      ACDS complex carries out an unusual reaction involving net cleavage of the acetyl
      C-C and thioester bonds of acetyl-CoA. The overall reaction is composed of
      several partial reactions, one of which involves catalysis of acetyl group
      transfer. To gain insight into the overall reaction, a study was carried out on
      the kinetics and mechanism of the acetyltransferase partial reaction. Analysis by
      HPLC was used to quantify rates of acetyl transfer from acetyl-CoA both to 3'
      dephospho-CoA and, by isotope exchange, to 14C-labeled CoA. Acetyl transfer
      activity was observed only under strongly reducing conditions, and was half
      maximal at -486 mV at pH 6.5. The midpoint activation potential became
      increasingly more negative as the pH was increased, indicating the involvement of
      a protonation step. Cooperative dependence on acetyl-CoA concentration was
      exhibited in reactions that contained incompletely reduced enzyme; however, under
      redox conditions supporting maximum activity, hyperbolic kinetics were found. A
      ping-pong steady state kinetic mechanism was established, consistent with
      formation of an acetyl-enzyme intermediate. Analysis of the inhibitory effects of
      CoA on acetyl transfer to 3'-dephospho-CoA provided values for KiCoA of 6.8
      microM and for Kiacetyl-CoA of 45 microM; isotope exchange analyses yielded
      values of 32 and 120 microM, respectively. Two separate measures of stability
      yielded values for the free energy of hydrolysis of the acetyl-enzyme
      intermediate of -9.6 and -9.3 kcal/mol, an indication of a high-energy bonding
      interaction in the acetyl-enzyme species. Implications for the mechanism of C-C
      bond cleavage are discussed.

PMID- 9772178
TI  - Transient kinetics of formation and reaction of the uridylyl-enzyme form of
      galactose-1-P uridylyltransferase and its Q168R-variant: insight into the
      molecular basis of galactosemia.
AB  - Galactose-1-phosphate uridylyltransferase catalyzes the reaction of UDP-glucose
      with galactose 1-phosphate (Gal-1-P) to form UDP-galactose and glucose 1
      phosphate (Glc-1-P) through a double displacement mechanism, with the
      intermediate formation of a covalent uridylyl-enzyme (UMP enzyme). Gln 168 in E.
      coli uridylyltransferase engages in hydrogen bonding with the phosphoryl oxygens
      of the UMP moiety, which is bonded to His 166 in the intermediate [Wedekind, J.
      E., Frey, P. A., and Rayment, I. (1996) Biochemistry 35, 11560-11569]. In humans,
      the point variant Q188R accounts for 60% of galactosemia cases. The corresponding
      E. coli variant Q168R has been overexpressed and purified. In preparation for
      kinetic correlation of Q168R and wild-type uridylyltransferases, we tested the
      kinetic competence of the wild-type UMP-enzyme. At 4 degreesC, the first-order
      rate constant for uridylylation by UDP-glucose is 281 +/- 18 s-1, and for
      deuridylylation it is 226 +/- 10 s-1 with Glc-1-P and 166 +/- 10 s-1 with Gal-1
      P. Inasmuch as the overall turnover number at 4 degreesC is 62 s-1, the covalent
      intermediate is kinetically competent. The variant Q168R is uridylylated by UDP
      glucose to the extent of about 65% of the potential active sites. Uridylylation
      reactions of Q168R with UDP-glucose proceed with maximum first-order rate
      constants of 2.2 x 10(-)4 s-1 and 4.2 x 10(-)4 s-1 at 4 and 27 degreesC,
      respectively. In experiments with uridylyl-Q168R and glucose-1-P, the mutant
      enzyme undergoes deuridylylation with maximum first-order rate constants of 4.8 x
      10(-)4 s-1 and 1.68 x 10(-)3 s-1 at 4 and 27 degreesC, respectively. The value of
      Km for uridylylation of Q168R is slightly higher than for the wild-type enzyme,
      and for deuridylylation it is similar to the wild-type value. The wild-type
      enzyme undergoes uridylylation and deuridylyation about 10(6) times faster than
      Q168R. The wild-type activity in the overall reaction is 1.8 x 10(6) times that
      of Q168R. The wild-type enzyme contains 1.9 mol of Zn+Fe per mole of subunits,
      whereas the Q168R-variant contains 1.36 mol of Zn+Fe per mole of subunits. The
      mutation stabilizes the uridylyl-enzyme by 1.2 kcal mol-1 in comparison to the
      wild-type enzyme. These results show that the low activity of Q168R is not due to
      overstabilization of the intermediate or to the absence of structural metal ions.
      Instead, the main defect is very slow uridylylation and deuridylation.

PMID- 9772179
TI  - Folding kinetics of villin 14T, a protein domain with a central beta-sheet and
      two hydrophobic cores.
AB  - The thermodynamics and kinetics of folding are characterized for villin 14T, a
      126-residue protein domain. Equilibrium fluorescence measurements reveal that
      villin 14T unfolds and refolds reversibly. The folding kinetics was monitored
      using stopped-flow with fluorescence and quenched-flow with NMR and mass
      spectrometry. Unfolding occurs in a single-exponential phase in the stopped-flow
      experiments, and about 75% of the total amplitude is recovered in the fast phase
      of refolding. The remaining 25% of the amplitude probably represents trapping in
      cis-trans proline isomerization pathways. At 25 degreesC, the stability estimate
      obtained by extrapolation from the transition region of the stopped-flow chevron
      matches the stability value from equilibrium urea titrations (DeltaG = 9.7
      kcal/mol, m value = 2.2 kcal mol-1 M-1). At low final urea concentrations,
      however, the refolding kinetics deviates from the two-state model, indicating the
      formation of an intermediate. Under these conditions, quenched-flow followed by
      NMR and mass spectrometry show no detectable hydrogen-bonded intermediate in the
      fast refolding phase. In contrast, agreement is observed between the equilibrium
      and kinetic estimates of stability at 37 degreesC (DeltaG = 6.0 kcal/mol, m value
      = 1.6 kcal mol-1 M-1), at all observed urea concentrations, demonstrating
      apparent two-state folding at this temperature. This result shows that the two
      state folding model, previously applied to small domains with single, central
      hydrophobic cores, can also describe the folding of a larger domain with multiple
      core structures.

PMID- 9772180
TI  - Conformational modulation of troponin T by configuration of the NH2-terminal
      variable region and functional effects.
AB  - Troponin T (TnT) is an essential element in the thin filament-based regulatory
      system of striated muscle. Alternative mRNA splicing generates multiple TnT
      isoforms with primary structural differences in the NH2-terminal region. The
      functional significance of this hypervariable NH2-terminal domain and the
      developmental or muscle type-specific TnT isoforms is not fully understood. We
      have analyzed chicken breast muscle TnT containing a metal-binding cluster
      [H(E/A)EAH]4-7 (Tx) in the NH2-terminal region to demonstrate potential effects
      of the NH2-terminal structure on the conformation of TnT [Ogut, O., and Jin, J.
      P. (1996) Biochemistry 35, 16581-16590]. Using specific antibody epitope analysis
      on this metal-binding TnT model, this study revealed that the binding of Zn2+ to
      the NH2-terminal region of chicken breast muscle TnT induces extensive
      conformational changes in the whole protein as demonstrated by a significant
      decrease in binding avidity of a polyclonal anti-TnT serum which recognizes
      multiple epitopes on the TnT molecule. This NH2-terminal configuration-based
      effect is not restricted to the metal ion interaction, whereas the binding of
      anti-NH2 terminus monoclonal antibodies to TnT induced similar changes. Protein
      binding assays have shown that the NH2-terminal variability-induced
      conformational changes can alter TnT's binding affinity for tropomyosin and
      troponin I. The results suggest a functional modulation of TnT through the
      configuration of the NH2-terminal domain, and this novel mechanism may mediate
      the physiological significance of the TnT isoform regulation.

PMID- 9772181
TI  - Influence of tightly bound Mg2+ and Ca2+, nucleotides, and phalloidin on the
      microsecond torsional flexibility of F-actin.
AB  - To better understand the relationship between structure and molecular dynamics in
      F-actin, we have monitored the torsional flexibility of actin filaments as a
      function of the type of tightly bound divalent cation (Ca2+ or Mg2+) or
      nucleotide (ATP or ADP), the level of inorganic phosphate and analogues, KCl
      concentration, and the level of phalloidin. Torsional flexibility on the
      microsecond time scale was monitored by measuring the steady-state
      phosphorescence emission anisotropy (rFA) of the triplet probe erythrosin-5
      iodoacetamide covalently bound to Cys-374 of skeletal muscle actin;
      extrapolations to an infinite actin concentration corrected the measured
      anisotropy values for the influence of variable amounts of rotationally mobile G
      actin in solution. The type of tightly bound divalent cation modulated the
      torsional flexibility of F-actin polymerized in the presence of ATP; filaments
      with Mg2+ bound (rFA = 0.066) at the active site cleft were more flexible than
      those with Ca2+ bound (rFA = 0.083). Filaments prepared from G-actin in the
      presence of MgADP were more flexible (rFA = 0.051) than those polymerized with
      MgATP; the addition of exogenous inorganic phosphate or beryllium trifluoride to
      ADP filaments, however, decreased the filament flexibility (increased the
      anisotropy) to that seen in the presence of MgATP. While variations in KCl
      concentration from 0 to 150 mM did not modulate the torsional flexibility of the
      filament, the binding of phalloidin decreased the torsional flexibility of all
      filaments regardless of the type of cation or nucleotide bound at the active
      site. These results emphasize the dynamic malleability of the actin filament, the
      role of the cation-nucleotide complex in modulating the torsional flexibility,
      and suggest that the structural differences that have previously been seen in
      electron micrographs of actin filaments manifest themselves as differences in
      torsional flexibility of the filament.

PMID- 9772182
TI  - Structural determinants of Ca2+ exchange and affinity in the C terminal of
      cardiac troponin C.
AB  - The C terminal of cardiac troponin C (TnC) has two Ca2+-Mg2+ sites which exhibit
      approximately 20-fold higher Ca2+ affinity than the two C-terminal Ca2+ specific
      sites in calmodulin (CaM). Substitution of the third EF-hand of TnC for the
      corresponding EF-hand of CaM produced a mutant (CaM[3TnC]) with a 10-fold higher
      C-terminal Ca2+ and Mg2+ affinity. Substitution of loop 3 of TnC for loop 3 of
      CaM produced a mutant (CaM[loop3TnC]) with a 10-fold faster Ca2+ on rate and a 5
      fold faster Ca2+ off rate than CaM. A mutant CaM (CaM[loop3X, Z]) which contained
      the identical coordinating amino acids and X and Z acid pairs of TnC loop 3 had a
      3-fold higher C-terminal Ca2+ affinity without the increased Ca2+ exchange rates
      exhibited by CaM[loop3TnC]. Thus, loop factors other than the acid pairs must be
      responsible for the rapid Ca2+ exchange rates of CaM[loop3TnC]. Helix 6 and helix
      5 in the third EF-hand of TnC support the rapid Ca2+ on rate of TnC's loop 3 and
      produce an approximately 4-fold reduction in its Ca2+ off rate, explaining the
      high Ca2+ affinity of the third EF-hand of TnC. Exchanging loop 3 or helix 5 of
      TnC into CaM increased the Mg2+ affinity by decreasing the Mg2+ off rate. Our
      results are consistent with the high Ca2+ and Mg2+ affinity of the third EF-hand
      of TnC resulting from the two (X and Z) acid pairs in loop 3, coupled with the
      greater hydrophobicity of helix 6 and helix 5 compared to that of the third EF
      hand of CaM.

PMID- 9772183
TI  - Probing the structure of the nicotinic acetylcholine receptor with the
      hydrophobic photoreactive probes [125I]TID-BE and [125I]TIDPC/16.
AB  - The hydrophobic photoreactive compound 3-trifluoromethyl-3-(m-[125I]iodophenyl)
      diazirine ([125I]TID) has revealed important structural information about the
      pore of the ion channel and lipid-protein interface of the nicotinic
      acetylcholine receptor (AChR). To further characterize the structure of the AChR,
      we have mapped the sites of photoincorporation of a benzoic acid ester analogue
      of TID ([125I]TID-BE) and a phospholipid analogue ([125I]TIDPC/16). For each
      photoreactive probe, labeled sites were identified by amino-terminal sequencing
      of purified tryptic fragments of individual receptor subunits. [125I]TID-BE
      reacted with alphaCys-412, alphaMet-415, and alphaCys-418 in the M4 segment of
      the alpha-subunit and gammaCys-451 and gammaSer-460 in gammaM4. In the M1 segment
      of the alpha- and beta-subunits, [125I]TID-BE labeled alphaPhe-227, alphaLeu-228,
      and betaLeu-234, betaAla-235, respectively. The labeling pattern in the M1 and M4
      segments indicate that TID and TID-BE interact with the AChR lipid-protein
      interface in a similar fashion, revealing the same lipid-exposed face of each
      transmembrane segment. In contrast to TID, there was, however, no detectable
      incorporation of [125I]TID-BE into the channel lining betaM2 segment when the
      AChR was labeled in the resting state conformation. In the presence of agonist
      (desensitized state), [125I]TID-BE reacted with betaLeu-257, betaVal-261, and
      beta-Leu-264 in betaM2; a labeling pattern which indicates that, in comparison to
      TID, the binding loci for TID-BE is located closer to the extracellular end of
      the channel. For [125I]TIDPC/16, receptor labeling was insensitive to the
      presence of agonist and the sites of incorporation mapped to the confines of the
      transmembrane segments alphaM4, alphaM1, and gammaM4, validating previous results
      found with small lipophilic probes.

PMID- 9772184
TI  - Selective ceramide binding to protein kinase C-alpha and -delta isoenzymes in
      renal mesangial cells.
AB  - Ceramide is an important lipid second messenger produced by sphingolipid
      metabolism in cells exposed to a limited number of agonists and in turn triggers
      several cell responses in a protein kinase C (PKC)-dependent manner. Stimulation
      of mesangial cells with a radioiodinated photoaffinity labeling analogue of
      ceramide, (N-[3-[[[2-(125I)iodo-4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benz yl]
      oxy]carbonyl]propanoyl]-D-erythro-sphingosine) ([125I]-TID-ceramide), defines PKC
      alpha and PKC-delta as direct targets of ceramide. No binding of ceramide to PKC
      epsilon and PKC-zeta could be detected. Moreover, TID-ceramide selectively binds
      to recombinant PKC-alpha and -delta but not to PKC-epsilon and -zeta isoenzymes.
      In vitro kinase activity assays reveal that only the binding of ceramide to PKC
      alpha is accompanied by an increase in kinase activity. In contrast, there is no
      change in in vitro kinase activity of the other isoforms tested, i.e., PKC-delta,
      -epsilon, and -zeta, toward any of the conventional substrates tested. However,
      it is noteworthy that PKC-delta shows a decreased autophosphorylation upon
      ceramide binding. In vivo, activation of PKC-alpha by ceramide is monitored by a
      delayed translocation of the isoform from the cytosol to the membrane fraction,
      detectable after 1 h of stimulation. In contrast, neither PKC-delta, nor -epsilon
      nor -zeta is redistributed by ceramide. One functional cell response mediated by
      PKC-alpha in mesangial cells is a negative feedback regulation of ligand
      stimulated phosphoinositide hydrolysis. When cells are pretreated with ceramide,
      ATP-induced inositol trisphosphate formation is time-dependently reduced. A
      maximal inhibition is observed after 2 h of ceramide exposure. In summary, these
      results suggest that ceramide selectively interacts with the alpha- and delta
      isoforms of PKC in mesangial cells. Whereas PKC-alpha is activated with
      pronounced inhibition of hormone-stimulated phosphoinositide signaling, PKC-delta
      displays a decrease in its autophosphorylation, suggesting a negative role of
      ceramide binding on PKC-delta activity.

PMID- 9772185
TI  - Identification of a membrane-spanning domain of the thiol-activated pore-forming
      toxin Clostridium perfringens perfringolysin O: an alpha-helical to beta-sheet
      transition identified by fluorescence spectroscopy.
AB  - Clostridium perfringens perfringolysin O (PFO or theta-toxin) is a cytolytic
      toxin that binds to cholesterol-containing membranes and then self-associates to
      spontaneously form aqueous pores of varying size in the bilayer. In this study, a
      membrane-spanning domain has been identified in PFO by a combination of
      fluorescence spectroscopic methods using the fluorescent dye N, N'-dimethyl-N
      (iodoacetyl)-N'-(7-nitrobenz-2-oxa-1, 3-diazolyl)ethylenediamine (NBD) whose
      emission properties are sensitive to water. PFO was substituted with a single
      cysteine at most of the residues between amino acids K189 and N218, and then each
      cysteine was modified with NBD. Each purified NBD-labeled PFO was then bound to
      membranes, and the probe's environment was ascertained by measuring its
      fluorescence lifetime, emission intensity, and collisional quenching with either
      aqueous (iodide ions) or nonaqueous (nitroxide-labeled phospholipids) quenchers.
      Lifetime and intensity measurements revealed that the amino acid side chains in
      this region of the membrane-bound PFO polypeptide alternated between being in an
      aqueous or a nonaqueous environment. This pattern indicates that this portion of
      the membrane-bound PFO spans the membrane in an antiparallel beta-sheet
      conformation. The alternating exposure of these residues to the hydrophobic
      interior of the bilayer was demonstrated by their susceptibility to quenching by
      nitroxide moieties attached to phospholipid acyl chains. Residues K189-N218
      therefore form a two-stranded, amphipathic beta-sheet in the membrane-bound PFO
      that creates a stable interface between the pore and the membrane. This same
      region packs as three short alpha-helices in the soluble, monomeric form of PFO,
      and therefore, the cholesterol-dependent conversion of PFO to a membrane-bound
      oligomer involves a major structural transition in which three alpha-helices
      unfold to form a membrane-spanning amphipathic beta-sheet.

PMID- 9772186
TI  - Stabilization of the phospho-aspartyl residue in a two-component signal
      transduction system in Thermotoga maritima.
AB  - The central signaling pathway in many bacterial regulatory systems involves
      phosphotransfer between two conserved proteins, a histidine protein kinase, and a
      response regulator. The occurrence of two-component signaling systems in
      thermophilic bacteria raises questions of how both the proteins and the labile
      acyl phosphate of the response regulator are adapted to function at elevated
      temperatures. Thermotoga maritima HpkA is a transmembrane histidine kinase, and
      DrrA is its cognate response regulator. Both DrrA and the cytoplasmic region of
      HpkA (HpkA57) have been expressed in Escherichia coli, purified, and
      characterized. HpkA57 and DrrA have apparent Tm's of 75 and 90 degreesC,
      respectively. HpkA57 exhibits ATP-dependent autophosphorylation activity similar
      to that of histidine kinases from mesophiles, with maximum activity at 70
      degreesC. DrrA catalyzes transfer of phosphoryl groups from HpkA57 and exhibits
      Mg2+-dependent autophosphatase activity, with maximum activity at approximately
      80 degreesC. At this temperature, the half-life for phospho-DrrA is approximately
      3 min. In the absence of Mg2+, the half-life is 26 min, significantly greater
      than the half-life of a typical acyl phosphate at 80 degreesC. In the absence of
      Mg2+, at all temperatures examined, phospho-DrrA exhibits much greater stability
      than acetyl phosphate. This suggests that the active site of this
      hyperthermophilic response regulator is designed to protect the phospho-aspartyl
      residue from hydrolysis.

PMID- 9772187
TI  - Identification and characterization of kinetically competent carbinolamine and
      alpha-iminoglutarate complexes in the glutamate dehydrogenase-catalyzed oxidation
      of L-glutamate using a multiwavelength transient state approach.
AB  - A highly constrained and heavily overdetermined multiwavelength transient state
      kinetic approach has been used to study the oxidative deamination of L-glutamate
      catalyzed by beef liver glutamate dehydrogenase. Spectra generated using the
      known enzyme-reduced coenzyme-substrate spectrum served as models for
      deconvolution of kinetic scan data. Deconvolution of the multiwavelength time
      course array shows formation of three distinguishable intermediates in the
      reaction sequence, an ultrablue-shifted complex, an ultrared-shifted complex, and
      a blue-shifted complex. The ultrablue-shifted entity is identified as the enzyme
      NADPH-alpha-iminoglutarate complex (ERI) and the ultrared as the enzyme-NADPH
      alpha-carbinolamine complex (ERC). The blue-shifted complex is characterized as
      the E-NADPH-ketoglutarate species (ERK). The location of these species along the
      reaction coordinate has been determined and their kinetic competency in the
      reaction sequence has been established by fitting the concentration time courses
      of the components for both the alpha-deuterio- and the alpha-protio-L-glutamate
      reactions to the now highly constrained differential equations derived from a
      kinetic scheme involving the sequential formation of alpha-iminoglutarate, alpha
      carbinolamine, and alpha-ketoglutarate-reduced coenzyme complexes, following the
      formation of two prehydride transfer complexes.

PMID- 9772188
TI  - Tryptophan synthase mutations that alter cofactor chemistry lead to mechanism
      based inactivation.
AB  - Mutations in the pyridoxal phosphate binding site of the tryptophan synthase beta
      subunit (S377D and S377E) alter cofactor chemistry [Jhee, K.-H., et al. (1998) J.
      Biol. Chem. 273, 11417-11422]. We now report that the S377D, S377E, and S377A
      beta2 subunits form alpha2 beta2 complexes with the alpha subunit and activate
      the alpha subunit-catalyzed cleavage of indole 3-glycerol phosphate. The apparent
      Kd for dissociation of the alpha and beta subunits is unaffected by the S377A
      mutation but is increased up to 500-fold by the S377D and S377E mutations.
      Although the three mutant alpha2 beta2 complexes exhibit very low activities in
      beta elimination and beta replacement reactions catalyzed at the beta site in the
      presence of Na+, the activities and spectroscopic properties of the S377A alpha2
      beta2 complex are partially repaired by addition of Cs+. The S377D and S377E
      alpha2 beta2 complexes, unlike the wild-type and S377A alpha2 beta2 complexes and
      the mutant beta2 subunits, undergo irreversible substrate-induced inactivation by
      L-serine or by beta-chloro-L-alanine. The rates of inactivation (kinact) are
      similar to the rates of catalysis (kcat). The partition ratios are very low
      (kcat/kinact = 0.25-3) and are affected by alpha subunit ligands and monovalent
      cations. The inactivation product released by alkali was shown by HPLC and by
      fluorescence, absorption, and mass spectroscopy to be identical to a compound
      previously synthesized from pyridoxal phosphate and pyruvate. We suggest that
      alterations in the cofactor chemistry that result from the engineered Asp377 in
      the active site of the beta subunit may promote the mechanism-based inactivation.

PMID- 9772189
TI  - Redox properties of human medium-chain acyl-CoA dehydrogenase, modulation by
      charged active-site amino acid residues.
AB  - The modulation of the electron-transfer properties of human medium-chain acyl-CoA
      dehydrogenase (hwtMCADH) has been studied using wild-type and site-directed
      mutants by determining their midpoint potentials at various pH values and
      estimating the involved pKs. The mutants used were E376D, in which the negative
      charge is retained; E376Q, in which one negative charge (pKa approximately 6. 0)
      is removed from the active center; E99G, in which a different negative charge
      (pKa approximately 7.3) also is affected; and E376H (pKa approximately 9.3) in
      which a positive charge is present. Em for hwtMCADH at pH 7.6 is -0.114 V.
      Results for the site-directed mutants indicate that loss of a negative charge in
      the active site causes a +0.033 V potential shift. This is consistent with the
      assumption that electrostatic interactions (as in the case of flavodoxins) and
      specific charges are important in the modulation of the electron-transfer
      properties of this class of dehydrogenases. Specifically, these charge
      interactions appear to correlate with the positive Em shift observed upon binding
      of substrate/product couple to MCADH [Lenn, N. D., Stankovich, M. T., and Liu, H.
      (1990) Biochemistry 29, 3709-3715], which coincides with a pK increase of Glu376
      COOH from approximately 6 to 8-9 [Rudik, I., Ghisla, S., and Thorpe, C. (1998)
      Biochemistry 37, 8437-8445]. From the pH dependence of the midpoint potentials of
      hwtMCADH two mechanistically important ionizations are estimated. The pKa value
      of approximately 6.0 is assigned to the catalytic base, Glu376-COOH, in the
      oxidized enzyme based on comparison with the pH behavior of the E376H mutant, it
      thus coincides with the pK value recently estimated [Vock, P., Engst, S., Eder,
      M., and Ghisla, S. (1998) Biochemistry 37, 1848-1860]. The pKa of approximately
      7.1 is assigned to Glu376-COOH in reduced hwtMCADH. Comparable values for these
      pKas for Glu376-COOH in pig kidney MCADH are pKox = 6.5 and pKred = 7.9. The Em
      measured for K304E-MCADH (a major mutant resulting in a deficiency syndrome) is
      essentially identical to that of hwtMCADH, indicating that the disordered enzyme
      has an intact active site.

PMID- 9772190
TI  - Trifluoroethanol promotes helix formation by destabilizing backbone exposure:
      desolvation rather than native hydrogen bonding defines the kinetic pathway of
      dimeric coiled coil folding.
AB  - We measure the effects of low concentrations of helix-stabilizing cosolvents,
      including 2,2,2-trifluoroethanol (TFE), on the thermodynamics and kinetics of
      folding of the dimeric alpha-helical coiled coil derived from the leucine zipper
      region of bZIP transcriptional activator GCN4. The change in kinetic behavior
      upon addition of 5% (v/v) TFE indicates that it stabilizes the transition state
      to the same degree as the fully helical native state. However, folding rates are
      largely insensitive to alanine to glycine mutagenesis, indicating that the
      majority of helical structure is formed after the transition state. Equilibrium
      hydrogen isotope partitioning measurements indicate that intramolecular hydrogen
      bonds are not strengthened by TFE and that amide hydrogen bonds in the transition
      state are nearly the same strength as those in the unfolded state. Thus, the
      mechanism by which TFE exerts its helix-stabilizing effects can be divorced from
      helix formation and does not depend on the strengthening of intrahelical hydrogen
      bonds. Rather, TFE increases the structure of the binary alcohol/water solvent,
      thereby increasing the energetic cost associated with solvation of the
      polypeptide backbone. At low concentrations, TFE destabilizes the unfolded
      species and thereby indirectly enhances the kinetics and thermodynamics of
      folding of the coiled coil. A high degree of polypeptide backbone desolvation,
      and not the formation of regular helical structure and native strength hydrogen
      bonds, is the critical feature of the transition state for folding of this small
      dimeric protein.

PMID- 9772191
TI  - Mechanism of reduced flavin transfer from Vibrio harveyi NADPH-FMN oxidoreductase
      to luciferase.
AB  - The mechanisms of reduced flavin transfer in biological systems are poorly
      understood at the present. The Vibrio harveyi NADPH-FMN oxidoreductase (FRP) and
      the luciferase pair were chosen as a model for the delineation of the reduced
      flavin transfer mechanism. FRP, which uses FMN as a cofactor to mediate the
      reduction of the flavin substrate by NADPH, exhibited a ping-pong kinetic pattern
      with a Km, FMN of 8 microM and a Km,NADPH of 20 microM in a single-enzyme
      spectrophotometric assay monitoring the NADPH oxidation. However, the kinetic
      mechanism of FRP was changed to a sequential pattern with a Km,FMN of 0.3 microM
      and a Km,NADPH of 0.02 microM in a luciferase-coupled assay measuring light
      emission. In contrast, the Photobacterium fischeri NAD(P)H-FMN oxidoreductase FRG
      showed the same ping-pong mechanism in both the single-enzyme spectrophotometric
      and the luciferase-coupled assays. Moreover, for the FRP, FMN at concentrations
      over 2 microM significantly inhibited the coupled reaction in both light
      intensity and quantum yield, and showed apparent noncompetitive and competitive
      inhibition patterns against NADPH and luciferase, respectively. No inhibition of
      the NADPH oxidation was detected under identical conditions. These results are
      consistent with a scheme that the reduced flavin cofactor of FRP is
      preferentially utilized by luciferase for light emission, the reduced flavin
      product generated by the reductase is primarily channeled into a dark oxidation,
      and luciferase competes against flavin substrate in reacting with the FRP reduced
      flavin cofactor. An FRP derivative containing 2-thioFMN as the cofactor was also
      used to further examine the mechanism of flavin transfer. Results again indicate
      a preferential utilization of the reductase reduced flavin cofactor by luciferase
      for the bioluminescence reaction.

PMID- 9772192
TI  - Raman and CD spectroscopy of recombinant 68-kDa DNA human topoisomerase I and its
      complex with suicide DNA-substrate.
AB  - N-terminally truncated recombinant 68-kDa human topoisomerase (topo) I exhibits
      the same DNA-driving activities as the wild-type protein. In the present study,
      Raman and circular dichroism techniques were employed for detailed structural
      characterization of the 68-kDa human topo I and its transformations induced by
      the suicide sequence-specific oligonucleotide (solig) binding and cleavage.
      Spectroscopic data combined with statistical prediction techniques were employed
      to construct a model of the secondary structure distribution along the primary
      protein structure in solution. The 68-kDa topo I was found to consist of ca. 59%
      alpha-helix, 24% beta-strand and/or sheets, and 17% other structures. A secondary
      structure transition of the 68-kDa topo I was found to accompany solig binding
      and cleavage. Nearly 15% of the alpha-helix of 68-kDa topo I is transferred
      within the other structures when in the complex with its DNA substrate. Raman
      spectroscopy analysis also shows redistribution of the structural rotamers of the
      68-kDa topo I disulfide bonds and significant changes in the H-bonding of the Tyr
      residues and in the microenvironment/conformation of the Trp side chains. No
      structural modifications of the DNA substrate were detected by spectroscopic
      techniques. The data presented provide the first direct experimental evidence of
      the human topo I conformational transition after the cleavage step in the
      reaction of binding and cleavage of DNA substrate by the enzyme. This evidence
      supports the model of the enzyme function requiring the protein conformational
      transition. The most probable location of the enzyme transformations was the core
      and the C-terminal conservative 68-kDa topo I structural domains. By contrast,
      the linker domain was found to have an extremely low potential for solig-induced
      structural transformations. The pattern of redistribution of protein secondary
      structures induced by solig binding and covalent suicide complex formation
      supports the model of an intramolecular bipartite mode of topo I/DNA interaction
      in the substrate binding and cleavage reaction.

PMID- 9772193
TI  - CO binding and valency exchange in asymmetric Hb hybrids.
AB  - There remains a major controversy concerning the properties of asymmetric
      hemoglobin hybrids, that is, doubly liganded tetramers consisting of an
      unliganded dimer and a liganded dimer. Different experimental evidence leads to
      opposing conclusions. Based on dimer-tetramer equilibrium studies, special "T
      like" properties were assigned to this hybrid (species 21), while the other
      biliganded tetramers were considered as similar to fully liganded Hb [Ackers et
      al. (1992) Science 255, 54-63]. We report here results for three types of
      experiment. In the first, the asymmetric hybrids are produced by
      photodissociating CO ligands from [dimer-CO/dimer-azido-met] hybrids. Since the
      CO association rates differ by over an order of magnitude for the two allosteric
      states, the CO kinetics are a sensitive probe of the tetramer conformation. The
      results show mainly rapid R-like kinetics for CO rebinding to the asymmetric
      hybrids. The second technique employs a stopped-flow apparatus to obtain a higher
      percentage and a longer equilibration time of the asymmetric hybrid. In this
      case, sodium dithionite is used to remove oxygen from a solution containing
      [dimer-oxy/dimer-azido-met] hybrids. After a fixed delay (but before loss of
      azide ligands), a second mixing with a buffer equilibrated under CO allows
      observation of CO binding to species 21. As for the flash measurements, the
      kinetics show predominantly rapid CO binding, typical of the liganded (R-state)
      tetramer. The rapid CO binding is not in agreement with the predictions of a T
      like conformation for species 21. One possible explanation is that the long
      incubation times used to study the dimer-tetramer equilibrium do not lead to a
      stable asymmetric hybrid, but rather a random distribution of oxidized subunits
      due to electron transfer between the iron atoms of the subunits [Shibayama et al.
      (1997) Biochemistry 36, 4375-4381]. We have repeated these experiments and
      confirm the valency exchange in a mixture of Hb A and S (or C) parent forms, as
      evidenced by compensating amounts of oxidation or reduction of the Hb parents.

PMID- 9772194
TI  - Endotoxin potentiates ozone-induced mucous cell metaplasia in rat nasal
      epithelium.
AB  - People are exposed to a combination of environmental pollutants throughout their
      lives. Repeated exposures of one common pollutant, ozone, have been reported to
      cause the development of mucous cell metaplasia in the nasal transitional
      epithelium (NTE) of rats. The present study was designed to test the hypothesis
      that exposure to bacterial endotoxin, another toxicant ubiquitous to the
      environment, potentiates this metaplastic response in rat NTE. Rats were exposed
      to 0 or 0.5 ppm ozone 8 h/day for 3 days. After ozone exposure, rats were
      intranasally instilled with saline containing 0 or 100 micrograms endotoxin once
      daily for 2 days. Rats were killed 6 h or 3 days after the last intranasal
      instillation. Nasal tissue was processed for light microscopy and image analysis,
      or for isolation of total RNA. Mucous cell metaplasia was not detected in
      air/endotoxin-exposed rats, was observed in ozone/saline-exposed rats, and was
      most severe in ozone/endotoxin-exposed rats. At 6 h after instillation, amounts
      of intraepithelial mucosubstances (IM) were 4-fold greater in NTE of
      ozone/endotoxin-exposed rats as compared to controls. These IM levels were
      similar to those of ozone/saline-exposed rats. Mucin-specific mRNA (rMuc-5AC)
      levels were elevated in all treatment groups at this timepoint. At 3 days after
      instillation, amounts of IM in ozone/endotoxin-exposed rats were 10-fold greater
      than in controls and 5-fold greater than in ozone/saline-exposed rats. rMuc-5AC
      mRNA levels remained elevated in the ozone/endotoxin-exposed rats. Despite the
      fact that bacterial endotoxin alone does not cause a phenotypic change in rat
      NTE, it can augment the mucous cell metaplasia induced by a previous exposure to
      ozone.

PMID- 9772195
TI  - Tamoxifen inhibits induction of the mitochondrial permeability transition by Ca2+
      and inorganic phosphate.
AB  - Tamoxifen (TAM) is a synthetic, nonsteroidal antiestrogenic agent that is widely
      prescribed in the treatment of estrogen-dependent neoplasias, including breast
      cancer. The mechanism of action has yet to be defined, but likely is independent
      of estrogen receptor binding. In light of its high lipophilicity and peroxyl
      radical scavenging activities, we hypothesized that TAM might be an effective
      inhibitor of the mitochondrial permeability transition (MPT), which is widely
      implicated in the mechanisms of chemical-induced tissue injury and apoptosis. The
      MPT was induced in vitro by incubating freshly isolated rat liver mitochondria in
      1 mM Pi with increasing concentrations of calcium. Induction of the MPT was
      characterized by the calcium-dependent depolarization of mitochondrial membrane
      potential, release of matrix calcium, and large amplitude swelling. Membrane
      potential and calcium release were measured with ion-selective electrodes;
      mitochondrial swelling was monitored spectrophotometrically. Preincubation with
      either cyclosporine A or TAM prevented, in a dose-dependent manner, the calcium
      induced MPT. TAM also inhibited the calcium-induced release of matrix
      glutathione. TAM caused a time-dependent reversal of both the calcium-induced
      membrane depolarization and calcium release, suggesting that the effect was on
      the permeability transition pore and not due to inhibition of the mitochondrial
      calcium uniport. The results suggest that TAM mimics cyclosporine A to inhibit
      induction of the MPT and that this activity is not related to the antioxidant
      properties of TAM.

PMID- 9772197
TI  - Immunotoxicologic effects of inhaled chromium: role of particle solubility and co
      exposure to ozone.
AB  - Soluble and insoluble hexavalent chromium (Cr6+) agents are concomitantly
      released with ozone (O3) during welding. Although pulmonary/immunologic
      implications from exposure to each agent individually have been investigated, the
      effects from simultaneous exposure, as occurs under actual working conditions,
      are unclear. To investigate immunomodulatory effects of inhaled Cr6+, F-344 rats
      were exposed for 5 h/day, 5 days/week for 2 or 4 weeks to atmospheres containing
      soluble potassium chromate (K2CrO4) or insoluble barium chromate (BaCrO4), each
      alone at 360 micrograms Cr/m3 or in combination with 0.3 ppm O3. One day after
      the final exposure, rats were euthanized, their lungs were lavaged, and pulmonary
      macrophages (PAM) were recovered for assessment of basal and inducible functions.
      Rats inhaling K2CrO4-containing atmospheres had greater levels of total
      recoverable cells, neutrophils, and monocytes in bronchopulmonary lavage compared
      to rats exposed to insoluble Cr6+ atmospheres, O3 alone, or air; these rats also
      had a reduced percentage of PAM, although total PAM levels remained unaffected.
      Although Cr exposure-related changes in PAM functionality were evident, any
      dependence upon Cr solubility was variable. K2CrO4-containing atmospheres
      modulated PAM-inducible interleukins-1 and -6, and tumor necrosis factor-alpha
      production to a greater degree than those containing BaCrO4. Conversely, BaCrO4
      containing atmospheres affected PAM basal nitric oxide production and interferon
      gamma-primed/zymosan-stimulated reactive oxygen intermediate production to a
      greater extent than did those containing K2CrO4. In none of the PAM assays did co
      inhalation of O3 result in a modulation of the effects obtained with either Cr6+
      compound itself. The results indicate that, while immunomodulatory effects of
      inhaled Cr6+ upon PAM are related to particle solubility, the co-inhalation of O3
      apparently does not cause further modifications of the metal-induced effects.

PMID- 9772196
TI  - Acute inhibition of spontaneous uterine contractions by an estrogenic
      polychlorinated biphenyl is associated with disruption of gap junctional
      communication.
AB  - An estrogenic polychlorinated biphenyl, 4-hydroxy-2',4', 6'-trichlorobiphenyl (4
      OH-TCB), inhibits oscillatory uterine contractions immediately. Because increased
      gap junction formation is associated with the development of synchronized uterine
      contractions at term, we examined whether the inhibitory effect of 4-OH-TCB on
      spontaneous oscillatory contractions was due to the disruption of gap junctional
      communication. The effect of 4-OH-TCB on gap junctional communication was
      determined by intercellular Lucifer yellow dye transfer in primary cultures of
      myometrial myocytes isolated from midgestation rats. Intercellular dye transfer
      was inhibited by 4-OH-TCB or 17beta-estradiol in a concentration-dependent
      manner. The inhibitory effect of 4-OH-TCB on intercellular dye transfer was
      reversed by tetraethylammonium (TEA). To examine effects on uterine contraction,
      longitudinal uterine strips were excised from midgestation rats and placed in
      muscle baths for isometric force measurement. Spontaneous uterine oscillation was
      suppressed by 4-OH-TCB or 17beta-estradiol. The inhibitory effects of 4-OH-TCB
      and 17beta-estradiol on spontaneous oscillations were counteracted by TEA but
      were not affected by a calcium ionophore (A23187) or a calcium-dependent
      potassium channel blocker (apamin). These results suggest that the acute
      inhibition of spontaneous oscillatory contractions by an estrogenic
      polychlorinated biphenyl may result from the disruption of intercellular
      communication.

PMID- 9772198
TI  - Phytoestrogens act as estrogen agonists in an estrogen-responsive pituitary cell
      line.
AB  - There is renewed interest in the medicinal value of natural plant products. One
      group of plant compounds, the phytoestrogens (PE), has been given considerable
      attention due to their ability to decrease the incidence of certain estrogen
      dependent cancers. In this study, we evaluate the effects of PE on estrogen
      dependent pituitary tumor cells by using the immortalized pituitary cell line
      PR1. Several PE were found to be active in PR1 cells, in that they bound to the
      estrogen receptor (ER), stimulated growth of PR1 cells, and induced an estrogenic
      response, prolactin secretion. The PE genistein, coumestrol, and zearalenone
      bound to the ER present in PR1 cells with an affinity 100-times lower than that
      of estradiol. However, resveratrol, a plant antitumor agent found in grapes,
      showed no significant binding to the ER. Zearalenone, coumestrol, and genistein
      were found to induce prolactin secretion and to stimulate growth, whereas
      resveratrol showed prolactin secretion but no growth stimulation. The estrogenic
      effects of PE in PR1 cells were ER dependent, in that addition of the
      antiestrogen ICI-182,780 inhibited prolactin response. Although resveratrol did
      not bind to the ER or stimulate growth, it induced prolactin secretion in both a
      dose- and time-dependent manner. The data presented here demonstrate that PE are
      active in lactotroph cells of the pituitary.

PMID- 9772199
TI  - Scavestrogens protect IMR 32 cells from oxidative stress-induced cell death.
AB  - Oxidative stress is considered an important pathophysiological mechanism
      contributing to promote cell death in a broad variety of diseases including
      cardiovascular and neurodegenerative disorders. The so-called scavestrogens J811
      and J861, structurally derived from 17alpha-estradiol, are potent radical
      scavengers and inhibitors of iron-induced cell damage in vitro. In this study the
      potential cytoprotective effects of the scavestrogens J811 and J861 against
      Fenton reagent-induced cell damage (50 microM FeSO4 plus 200 microM H2O2) were
      compared with those of 17alpha- and 17beta-estradiol. Cell viability studies
      using Trypan blue staining showed that estradiols and scavestrogens at
      concentrations ranging from 0.1 to 10 microM are able to protect IMR 32
      neuroblastoma cells from Fenton-mediated death. In addition, these compounds
      decreased lipid peroxidation measured as thiobarbituric acid reactive substances
      and renormalize oxidative stress-increased intracellular glutathione levels. When
      given 6 h after the toxic stimulus, J811 and J861 rescued 60% of cells, whereas
      17alpha- and 17beta-estradiol were ineffective. These results suggest that the
      scavestrogens J811 and J861 are powerful antioxidants capable of interfering with
      radical-mediated cell death in diseases known to be aggravated by reactive oxygen
      species. Such compounds may be useful in the development of novel treatments for
      stroke or neurodegenerative disorders.

PMID- 9772200
TI  - Gestational exposure to chlorpyrifos: apparent protection of the fetus?
AB  - Previous studies have shown that, in general, young, postnatal animals are more
      sensitive than adults to the toxic effects of anticholinesterase (antiChE)
      pesticides. Paradoxically, often fetal brain cholinesterase (ChE) is less
      inhibited than maternal brain after gestational exposure to an antiChE,
      presumably due to placental and fetal detoxification of the antiChE. The present
      investigation was designed to study selected toxicokinetic and toxicodynamic
      factors surrounding the toxicity of chlorpyrifos (CPF; [O,O'-diethyl O-3,5,6
      trichloro-2-pyridyl] phosphorothionate) in pregnant rats dosed repeatedly or
      singly during late gestation. Dams were dosed daily (po) with CPF in corn oil (0
      or 7 mg/kg) on gestational days (GD) 14 to 18. Animals were euthanized at 2 to
      120 h after the last dose and tissues were collected for enzyme analysis. Using
      this dosing regimen, we found that (1) the time of maximal ChE inhibition was the
      same (i.e., 5-10 h after dosing) for both maternal and fetal brain, (2) the
      degree of fetal brain ChE inhibition was 4.7 times less than maternal brain
      inhibition, and (3) the detoxification potential (i.e., carboxylesterase and
      chlorpyrifos-oxonase) of the fetal tissues was very low compared to the maternal
      tissues. A separate group of experiments showed that if pregnant dams received
      only one oral dose of 7 or 10 mg/kg CPF on GD18, the degree of ChE inhibition in
      the fetal brain was comparable to the maternal brain ChE inhibition. Taking into
      consideration the net increase (more than fourfold) in fetal brain ChE activity
      from GD14 to 18 in control animals, and the fact that maternal brain ChE was
      inhibited more than fetal brain ChE only in a repeated-dosing regimen, we
      conclude that the fetus is not genuinely protected from the toxic effects of a
      given dose of CPF. We propose that fetal brain ChE is simply able to recover more
      fully between each dose as compared to maternal brain ChE, giving the illusion
      that the fetal compartment is less affected than the maternal compartment.

PMID- 9772201
TI  - Airway morphology and function of rats following dermal sensitization and
      respiratory challenge with low molecular weight chemicals.
AB  - Local lymph node activation and increased total serum IgE levels are suggested to
      be predictive parameters of airway hypersensitivity caused by low molecular
      weight (LMW) chemicals. Whether increases of total serum IgE are indicative of
      actual induction of specific airway reactions (morphological and functional)
      after inhalation challenge was examined in the present study. In Brown Norway
      (BN) and Wistar rats, serum IgE concentrations were examined following topical
      exposure of chemicals with known diverse sensitization potential in humans:
      trimellitic anhydride (TMA), a dermal and respiratory sensitizer;
      dinitrochlorobenzene (DNCB), a dermal sensitizer with no known potential to cause
      respiratory allergy; and methyl salicylate, a skin irritant devoid of sensitizing
      properties. Functional and histopathological changes in the respiratory tract
      were examined after subsequent inhalatory challenge with these chemicals. Of the
      three tested chemicals, only topical exposure to TMA resulted in a significant
      increase in total serum IgE concentrations in the high-IgE-responding BN rat.
      Upon subsequent inhalatory challenge of these rats, TMA induced specific airway
      reactions which included a sharp decrease in respiratory rate during challenge,
      followed by an increase in breathing rate with a concomitant decrease in tidal
      volume 24 and 48 h after inhalatory challenge, and histopathological changes in
      the larynx and lungs of animals necropsied 48 h after challenge. Interestingly,
      despite low IgE levels, TMA induced histopathological changes in the larynx and
      lungs of Wistar rats too. Laryngeal changes were also observed in Wistar rats
      upon sensitization and challenge with DNCB. These data suggest that increased
      total serum IgE after topical sensitization is associated with immediate-type
      specific airway reactivity after inhalation challenge in BN rats and thus may be
      a valuable parameter in testing for respiratory sensitization potential of LMW
      compounds. Histopathological examination upon subsequent inhalation challenge of
      sensitized low-IgE-responders may provide information on other allergic
      inflammatory airway reactions.

PMID- 9772202
TI  - Low-level exposure to diquat induces a neurally mediated intestinal
      hypersecretion in rats: involvement of nitric oxide and mast cells.
AB  - Diquat, a nonselective desiccant herbicide, induces a significant secretion of
      fluid into the lumen of the gastrointestinal tract of rats at sublethal doses
      (from 0.5 to 50 mg/kg). This study investigated the effect of an acute low-level
      exposure to diquat (0. 1, 0.5, and 1 mg/kg) on intestinal net water flux and the
      mechanisms involved. In anesthetized rats, an intestinal loop (7 cm) was infused
      with Ringer's buffer containing [14C]-polyethylene glycol 4000. After
      equilibration, diquat (0.1, 0.5, and 1 mg/kg) was added to Ringer's buffer during
      60 min. Net water flux was calculated according to [14C] activity determined in
      the effluent collected at 15-min intervals. Infused in the intestinal loop for 60
      min at doses of 0.5 and 1 mg/kg but not at 0.1 mg/kg, diquat induced an
      intestinal net water secretion during 180 min with a maximal effect at the
      highest dose used and during the first hour following the end of diquat infusion.
      Diquat-induced (1 mg/kg) intestinal net water secretion was blocked by a
      neurotoxin, tetrodotoxin (5 micrograms/kg iv), doxantrazole (5 mg/kg ip), a mast
      cell stabilizer, and two inhibitors of NO synthases: l-NAME (25 mg/kg ip) and
      aminoguanidine (2 mg/kg ip). It is concluded that a single low-level (0.5 and 1
      mg/kg) intrajejunal administration of diquat induces a net water intestinal
      secretion and that this secretory effect is nerve-mediated, implying mast cell
      degranulation and NO release.

PMID- 9772203
TI  - The role of glutathione S-transferases as a defense against reactive
      electrophiles in the blood vessel wall.
AB  - The glutathione transferases (GSTs) are a family of ubiquitous enzymes that
      catalyze the conjugation of reduced glutathione (GSH) with reactive
      electrophiles. Rat vascular tissue contains GST isoforms that represent a major
      cellular defense mechanism against atherogenic alpha,beta-unsaturated aldehydes
      (Misra et al., Toxicol. Appl. Pharmacol. 133, 27-33, 1995). In this study we
      examined the role of GSTs in providing protection to cultured neonatal vascular
      smooth muscle cells (VSMCs) from the alpha,beta-unsaturated carbonyl
      cardiovascular toxins, allylamine and its metabolite, acrolein. Confluent
      cultured cells were exposed to 2 to 10 microM allylamine (a cardiovascular toxin
      that is metabolized in vivo and in vitro by VSMCs to the reactive aldehyde,
      acrolein) or to acrolein (2-10 microM) for 48 h; dose-cytotoxicity curves were
      generated utilizing a tetrazolium-dependent cytotoxicity assay. Concommittant
      treatment with sulfasalazine, an established inhibitor of GST, was found to
      markedly increase allylamine- or acrolein-induced cytotoxicity, decreasing the
      LC50 by two- to threefold at 50 to 100 microM sulfasalazine. A clonogenic
      survival assay in VSMCs exposed to these compounds for 4 h confirmed lethal
      toxicity and enhanced toxicity following cotreatment with sulfasalazine.
      Isobologram analysis (which statistically defines the limits of additivity of two
      independent treatments) showed that the sulfasalazine effect on both allylamine
      and acrolein cytotoxicity was supraadditive, or synergistic. Sulfasalazine was
      not cytotoxic to VSMCs in the range of concentrations that augmented acrolein or
      allylamine cytoxicity; total GST activity was inhibited, however, in a dose
      dependent manner in that range. GST purified by GSH-affinity chromatography from
      pelleted untreated cells gave specific activities and kinetic constants
      consistent with those previously reported for rat aorta total GSTs. The catalytic
      efficiency (Kcat/Vm) was found to be much greater for 4-hydroxy-2-nonenal than
      for 1-chloro-2,4-dinitrobenzene (0.058 vs 0.4 s-1 mM-1). Western blot of purified
      total GSTs using antibodies against rec-mGSTA4-4 revealed a single band at 25
      kDa, confirming the presence of a GST isozyme immunologically similar to rat GST8
      8, which is known to utilize alpha,beta-unsaturated carbonyls as preferred
      substrates. Our data indicate that GSTs are an important defense in the vascular
      media, protecting blood vessels against alpha,beta-unsaturated carbonyl
      cardiovascular toxins that are involved in initiating atherosclerotic lesions.

PMID- 9772204
TI  - Kinetics of trichloroacetic acid and dichloroacetic acid in the isolated perfused
      rat liver.
AB  - Trichloroacetic acid (TCA) and dichloroacetic acid (DCA) are environmental
      contaminants that are suspected human carcinogens. To obtain more detail on the
      role of the liver in the kinetics of TCA and DCA, experimental studies in the
      isolated perfused rat liver (IPRL) system were conducted. The IPRL system was
      dosed with either 5 or 50 micromol of either TCA or DCA (25 or 250 microM initial
      concentration, respectively). TCA and DCA concentrations were followed in
      perfusion medium and bile for 2 h. The chemical concentration in liver was
      determined at the end of exposure. Liver viability was monitored by measuring
      leakage of lactate dehydrogenase (LDH) into perfusion medium and the rate of bile
      production. Studies performed with TCA showed that the total TCA concentration in
      perfusion medium decreased slightly during the first 30 min of exposure and
      remained constant thereafter. Most TCA, greater than 90% of total, was bound to
      albumin in the perfusion medium. A low, linear excretion rate of TCA in bile was
      obtained. The calculated free TCA concentration in the liver intracellular water
      space was higher than the unbound TCA concentration in the perfusion medium.
      Parallel studies with DCA showed that the DCA concentration in perfusion medium
      decreased rapidly. Of the total DCA in the perfusion medium, 60% was bound to
      albumin. The concentration of DCA in bile decreased over time. There was no DCA
      detectable in the liver after 2 h of exposure at both DCA concentrations. Enzyme
      leakage and bile production did not change in the presence of TCA or DCA,
      indicating that these concentrations were not acutely cytotoxic to the liver.

PMID- 9772205
TI  - Myopathy induced by HMG-CoA reductase inhibitors in rabbits: a pathological,
      electrophysiological, and biochemical study.
AB  - A combination of electrophysiological, pathological, and biochemical studies were
      performed in myopathy induced by 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)
      reductase inhibitors. Simvastatin (a lipophilic inhibitor) or pravastatin (a
      hydrophilic inhibitor) were administered by gavage to rabbits. In Group I
      (simvastatin-treated group, 50 mg/kg/day for 4 weeks), four rabbits showed muscle
      necrosis and high serum creatine kinase (CK) levels, and all six rabbits showed
      electrical myotonia. In Group II (pravastatin-treated group, 100 mg/kg/day for 4
      weeks), no rabbit showed either condition. In Group III (pravastatin-treated
      group, 200 mg/kg/day for 3 weeks plus 300 mg/kg/day for 3 weeks), one rabbit
      showed muscle necrosis and high serum CK level and two rabbits showed electrical
      myotonia. The pathological findings were muscle fiber necrosis and degeneration
      with increased acid phosphatase activity by light microscopy, autophagic vacuoles
      and mitochondrial swelling, and disruption and hypercontraction of myofibrils by
      electron microscopy. Ubiquinone content decreased in skeletal muscle by 22 to 36%
      in Group I, by 18 to 52% in Group II, and by 49 to 72% in Group III. However,
      mitochondrial enzyme activities of respiratory chain were normal in all groups.
      These results indicate that myopathy was not induced by a secondary dysfunction
      of mitochondrial respiration due to low ubiquinone levels.

PMID- 9772206
TI  - Identification of a novel peroxisome proliferator responsive cDNA isolated from
      rat hepatocytes as the zinc-finger protein ZFP-37.
AB  - The implementation of a rat hepatocyte model system and differential display
      polymerase chain reaction resulted in the isolation of ZFP-37 as a peroxisome
      proliferator-responsive gene. In addition to being responsive to peroxisome
      proliferators, rat ZFP-37 (rZFP-37) mRNA accumulates rapidly after treating cells
      with several other hepatic tumor promoters, serum, and cycloheximide, indicating
      that this gene belongs to the immediate-early growth responsive gene family.
      Although rZFP-37 and mouse ZFP-37 (mZFP-37) are both members of the Kruppel
      associated box and C2H2 zinc finger superfamily of proteins, there are several
      features that distinguish the two proteins. The primary protein sequences of rat
      and mouse ZFP-37 are highly conserved, especially within the region encoding the
      12 C2H2 zinc finger motifs; however, a region believed to be involved in DNA
      binding in mZFP-37 is divergent in rZFP-37. Mouse ZFP-37 mRNA is expressed almost
      exclusively in testes and brain, whereas rZFP-37 mRNA is expressed in testes,
      brain, kidney, spleen, thymus, lung, and at low levels in liver. A major
      difference between regulation of ZFP-37 in the two species exists as rZFP-37 is
      induced, while mZFP-37 is repressed, in liver by the administration of the potent
      peroxisome proliferator Wy 14,643. Despite the fact that mZFP-37 is believed to
      be important in cell growth and differentiation in testes and brain, the
      pronounced differences in regulation of this gene in two closely related species
      preclude an extrapolation to rZFP-37's biological role. Nonetheless, the effects
      of tumor promoters and mitogens on its expression and the inclusion of rZFP-37
      into the immediate-early growth gene families raise the possibility that this
      gene plays a role in hepatocyte proliferation and/or differentiation.

PMID- 9772208
TI  - Digestive tract absorption of PCDD/Fs, PCBs, and HCB in humans: mass balances and
      mechanistic considerations.
AB  - Gastrointestinal absorption of polychlorinated dibenzo-p-dioxins (PCDDs),
      dibenzofurans (PCDFs), biphenyls (PCBs) and hexachlorobenzene (HCB) from food was
      investigated in seven individuals aged 24 to 81 years with different contaminant
      body burdens using a mass balance approach. The difference between the ingested
      and excreted amounts of the chlorinated compounds was defined as net absorption.
      No analyzed compound was absorbed completely, and some were excreted to a greater
      extent than ingested, resulting in a net excretion. The absorption behavior was
      predominantly controlled by blood lipid levels: good correlations were obtained
      between the net absorption and the lipid-based concentrations in the blood for
      almost all of the persistent compounds studied. Expressed in international
      toxicity equivalents (I-TEq), the maximum absorption of PCDD/Fs among the
      volunteers was 63% and, for the three oldest volunteers, a net excretion of I-TEq
      was found. The high absorption levels of many compounds could not be explained on
      the basis of diffusive gradients estimated from the difference between the lipid
      based food and blood concentrations; the diffusive gradient was consistently
      negative. Adding a factor to account for the reduction in the lipid content of
      the food during passage through the digestive tract did not resolve this problem.
      To explain this discrepancy, a "fat-flush" theory was postulated, which
      hypothesizes that the fat compartment of the absorbing tissue expands due to the
      uptake of dietary fat, resulting in a decrease of this compartment's lipid-based
      concentrations below the food's, hence facilitating absorption. The fat-flush
      hypothesis provides a theoretical basis for a two-step model of organic pollutant
      transfer in the gastrointestinal tract, with absorption and excretion as distinct
      processes occurring at different locations.

PMID- 9772207
TI  - Characterization of furazolidone apical-related effects to human polarized
      intestinal cells.
AB  - In studying the effects of furazolidone (FZ) on the human intestinal Caco-2 cell
      line grown on microporous membrane, we have previously demonstrated a higher
      toxicity when the compound was administered at the apical (AP) side than at the
      basolateral (BL) side. Moreover, we have also shown the production, in the intact
      cells, of a nitroanion radical from FZ by a cytochrome c P450 reductase. The aim
      of the present study was to investigate which specific cell structures and
      functions are involved in the observed domain-related toxicity. The relevance of
      alterations in integrity and selective properties of the intestinal barrier as
      first-pass site for ingested molecules is also discussed. We have confirmed that,
      as expected, the Caco-2 cells are protected from FZ injury by a specific
      inhibitor of the cytochrome c P450 reductase, and we have shown that this
      protection is more active on the apical side of the cells. In sublethal
      conditions, FZ causes increased permeability to 3H-mannitol and, to a different
      extent, to 3H-inulin. Again the effect is higher when the cells are apically
      exposed. We have thus examined the tight junctions morphology: a disruption of
      the apical perijunctional actin-bound cytoskeleton was detected by rhodamine
      phalloidin staining and microtubule disorganization by antitubulin
      fluoresceinated antibodies. Again, the effect was more evident when the cells
      were apically treated with FZ. Preferential transport and accumulation of the
      compound by active transport mechanisms could be excluded, since transport of FZ
      was linear and no intracellular accumulation was detected either from the AP and
      or the BL sides. All together these results may suggest that the AP formation of
      the active metabolite and its possible reactivity with SH groups of
      perijunctional microfilaments could be responsible of the higher FZ apical
      toxicity. This study shows that polarized differentiated cells are very
      interesting in vitro models to investigate specific cellular domains as targets
      of toxic effects and to detect subtle changes that may be induced, in absence of
      cell death, in specialized epithelial layers.

PMID- 9772209
TI  - Monocrotaline pyrrole interacts with actin and increases thrombin-mediated
      permeability in pulmonary artery endothelial cells.
AB  - One of the earliest morphologic changes evident in the monocrotaline (MCT) model
      of pulmonary hypertension in rats is microvascular leak. Whether this represents
      a direct effect of MCT metabolites or is secondary to inflammatory and thrombotic
      changes remains uncertain. To determine whether MCT directly affects endothelial
      cell permeability barrier function, we characterized the interaction of the
      reactive pyrrole intermediate of MCT (MCTP) with endothelial cell actin and
      characterized its effects on thrombin-mediated signal transduction and monolayer
      permeability. Bovine pulmonary endothelial cells (BPAEC) treated with MCTP had
      altered distribution of filamentous actin evident by fluorescence microscopy.
      Correlative Western blots and autoradiography of actin isolated from BPAEC
      treated with 14C-MCTP showed comigration of actin and MCTP-derived 14C. MCTP
      treatment did not alter cellular free Ca2+ concentrations nor did it interfere
      with thrombin-mediated intracellular Ca2+ signal. Pretreatment with MCTP
      significantly augmented the thrombin-mediated transudation of Evan's blue albumin
      in BPAEC monolayers apparently by increasing the size of intercellular gaps. We
      conclude that MCTP directly interacts with actin to alter its polymerization
      state but does not significantly affect endothelial cell response to contractile
      stimulus. Our results suggest that MCTP may affect endothelial cell barrier
      function through alterations in intracellular junctions.

PMID- 9772210
TI  - Location of aluminium and gallium in human neuroblastoma cells treated with metal
      chelating agent complexes.
AB  - The subcellular location of aluminium is unknown, probably because of
      difficulties in investigating aluminium biochemistry and the use of varied
      experimental approaches of uncertain sensitivity. We have studied levels of
      uptake and the localization of gallium and of aluminium in cultured human
      neuroblastoma cells treated with soluble metal complexes (mainly Al- or Ga-EDTA),
      radiolabeled with 26Al or 67Ga, respectively. Crude nuclei and cytoplasm were
      obtained by two separate methods, and DNA, RNA, and proteins were prepared from
      the nuclei by centrifugation in high salt; also, cytosol and noncytosol were
      separated using a nondissociating method. Levels of uptake were of similar order
      for the two metals-on average about 50 pmol/10(6) cells for aluminium and 120
      pmol/10(6) cells for gallium, after 4 to 8 days treatment at 250 microM, and
      approximately 50 to 70% of the metal was found in the cytosol. About 20% of the
      aluminium and 10 to 25% of the gallium was associated with nuclear protein. A
      lower proportion was bound to DNA and to nuclear RNA. In cells treated with
      gallium-citrate/transferrin mixtures, 30 to 35% of the gallium in the cytosol was
      bound to protein, at least 35 being loosely bound; the main gallium-associated
      protein was probably intracellular transferrin. The remaining 65 to 70% of the
      metal in the cytosol was in low-molecular-weight form, and we suggest that the
      latter metal could affect structures such as the cytoskeleton and also metabolic
      processes in the cytoplasm. The similarity in distribution of the two metals
      supports the use of gallium as a "surrogate" for aluminium, at least in cell
      culture studies.

PMID- 9772211
TI  - Interactive effects of three structurally different polychlorinated biphenyls in
      a rat liver tumor promotion bioassay.
AB  - Interactive effects between the non-ortho-substituted 3,3', 4,4', 5
      pentachlorobiphenyl (PCB126), the mono-ortho-substituted 2,3,3',4, 4'
      pentachlorobiphenyl (PCB105), and the di-ortho-substituted 2,2',4, 4',5,5'
      hexachlorobiphenyl (PCB153) were studied in an initiation/promotion bioassay.
      Female Sprague-Dawley rats were injected with 30 mg/kg ip of N
      nitrosodiethylamine 24 h after partial hepatectomy. Five weeks later, weekly sc
      administrations of the three PCBs in 15 systematically selected dose combinations
      started. After 20 weeks of administration, the animals were killed and the livers
      were analyzed for areas expressing placental glutathione-S-transferase as a
      marker of preneoplastic foci. In addition, concentration of liver and kidney
      retinoids and plasma retinol was analyzed, as well as body and organ weights,
      plasma transaminases, and induction of hepatic cytochrome P450 1A1/2 (CYP1A1/2)
      and CYP2B1/2 activities. Data were analyzed with a multivariate method. At the
      doses applied in this study, weak antagonism was observed between PCB126 and
      PCB153 for effects on volume fraction of foci, number of foci/cm3, concentration
      of plasma retinol and liver retinoids, relative liver weight, and induction of
      CYP2B1/2 activity. Weak antagonism was also observed between PCB126 and PCB105
      for effects on volume fraction of foci, number of foci/cm3, and plasma retinol
      concentration. No interactions other than pure additivity were observed between
      PCB105 and PCB153. Synergism was not observed within the dose ranges investigated
      in this study. Knowledge of interactive effects is important for risk assessment
      of environmental mixtures of dioxin-like compounds. Antagonism between congeners
      generally results in risk assessments that overestimate human risk. The
      significance to human risk assessment of the relatively weak antagonism observed
      in this study is however unclear, considering many other uncertainties involved
      in the toxic equivalency factor (TEF) concept. A change of the TEF concept for
      risk assessments of dioxin-like substances is not motivated based on the results
      of this study.

PMID- 9772212
TI  - Identification of amino acid residues essential for high aflatoxin B1-8,9-epoxide
      conjugation activity in alpha class glutathione S-transferases through site
      directed mutagenesis.
AB  - Mice constitutively express glutathione S-transferase mGSTA3-3 in liver. This
      isoform possesses uniquely high conjugating activity toward aflatoxin B1-8,9
      epoxide (AFBO), thereby protecting mice from aflatoxin B1-induced
      hepatocarcinogenicity. In contrast, rats constitutively express a closely related
      GST isoenzyme, rGSTA3-3, with low AFBO activity and, therefore, are sensitive to
      aflatoxin B1 exposure. Although the two GSTs share 86% sequence identity and have
      similar catalytic activities toward 1-chloro-2,4-dinitrobenzene (CDNB), they have
      an approximately 1000-fold difference in catalytic activity toward AFBO. To
      identify amino acids that confer high activity toward AFBO, non-conserved rGSTA3
      3 residues were replaced with mGSTA3-3 residues in two regions believed to form
      the substrate binding site. Twenty-one mutant rGSTA3-3 enzymes were generated by
      site-directed mutagenesis using combinations of nine different residues. Except
      for the E208D mutant, single mutations of rGSTA3-3 produced enzymes with no
      detectable AFBO activity. Generally, AFBO conjugation activity increased in
      additive fashion as mGSTA3-3 residues were introduced into the rGSTA3-3 enzyme
      with the six site mutant E104I/H108Y/Y111H/L207F/E208D/V217K displaying the
      highest AFBO activity (40 nmol/mg/min) of all the mutant enzymes. When this
      mutant enzyme was further modified by three additional substitutions
      (D103E/I105M/V106I) AFBO conjugation activity decreased 14-fold to 2. 8
      nmol/mg/min. Although wild-type mGSTA3-3 AFBO conjugation activity (265
      nmol/mg/min) could not be obtained by our rGSTA3-3 mutants, we were able to
      identify six mGSTA3-3 residues; Ile104, Tyr108, His111, Phe207, Asp208, and
      Lys217 that, when collectively substituted into rGSTA3-3, substantially increased
      (>200-fold) glutathione conjugation activity toward AFBO.

PMID- 9772213
TI  - Potential mechanisms of the enhancement of aldicarb toxicity to Japanese medaka,
      Oryzias latipes, at high salinity.
AB  - In an attempt to understand underlying mechanism(s) of salinity-induced aldicarb
      toxicity in Japanese medaka (Oryzias latipes), aldicarb uptake,
      biotransformation, and its effect on acetylcholinesterase (AChE) were examined.
      Salinity had no effect on aldicarb uptake. However, gill microsomal flavin
      containing monooxygenase (FMO) activity and a 57-kDa FMO1-like protein increased
      as the salinity was raised from 0.15 to 2.0%. Sulfoxidation of 14C-aldicarb by
      liver and gill microsomal incubations showed ninefold and 1.8-fold increases,
      respectively, as the salinity was raised from 0.15 to 2.0%. Formation of aldicarb
      sulfoxide was not affected by incubation with carbon monoxide, indicating that
      cytochrome P450 (CYP450) was not a primary pathway in the formation of the
      sulfoxide. Muscle AChE activity showed no significant relationship with salinity,
      although the IC50 of aldicarb to muscle AChE differed significantly between 6.21
      +/- 1. 253 and 2.97 +/- 0.597 microM for 0.15 and 2.0% salinity, respectively.
      Aldicarb sulfoxide was 40 times more potent than aldicarb in inhibiting muscle
      AChE in Japanese medaka. Based on these results, we conclude that salinity
      induced enhancement of aldicarb toxicity to Japanese medaka might be partly
      attributed to the upregulation of FMO(s), which, in turn, increase the
      biotransformation of aldicarb to aldicarb sulfoxide, which is a more potent
      inhibitor of AChE than aldicarb. In addition, salinity also seems to potentiate
      the anticholinesterase activity of aldicarb (the parent) through an unknown
      mechanism.

PMID- 9772214
TI  - Absence of a protective effect of the oxime 2-PAM toward paraoxon-poisoned honey
      bees: acetylcholinesterase reactivation not at fault.
AB  - We investigated the failure of 2-PAM to protect honey bees against poisoning with
      paraoxon. The protective effect of the oxime 2-PAM against inhibition of
      acetylcholinesterase (AChE) by paraoxon was estimated in vitro and in vivo and
      was correlated with the mortality of paraoxon-treated bees. In vitro, 2-PAM
      protected 90% of AChE activity in the presence of paraoxon and reactivated more
      than 90% of inhibited AChE. Minor soluble and major membrane-bound forms of bee
      AChE presented about similar extents of reactivation, but the first order rate
      constant of reactivation (kobs) of the soluble form is threefold higher than that
      of the membrane-bound form. However, this difference did not significantly
      influence the reactivation kinetics of total AChE; the constant kobs of the
      membrane-bound form reflected that of total AChE. The linear kinetic profile of
      total AChE reactivation supported the conclusion that there was a single
      population of reactivatable species. The bimolecular rate constant of
      reactivation (kr), the dephosphorylation rate constant (k2), and the dissociation
      constant (Kd) were 646 M-1.min-1, 0.84 min-1 and 1. 30 mM, respectively. In vivo,
      administration of 2-PAM, after paraoxon exposure, induced a complete protection
      of AChE activity, but did not elicit any significant effect on mortality in
      paraoxon-treated bees. The inefficiency of 2-PAM to antagonize paraoxon-induced
      mortality was not changed by the administration of 2-PAM in pretreatment-therapy
      and in therapy treatments. These results indicated that the mortality of paraoxon
      poisoned honey bees was not due to a lack of AChE reactivation.

PMID- 9772215
TI  - Protection against acetaminophen toxicity in CYP1A2 and CYP2E1 double-null mice.
AB  - Acetaminophen (APAP) hepatotoxicity is due to its biotransformation to a reactive
      metabolite, N-acetyl-p-benzoquinone imine (NAPQI), that is capable of binding to
      cellular macromolecules. At least two forms of cytochrome P450, CYP2E1 and
      CYP1A2, have been implicated in this reaction in mice. To test the combined roles
      of CYP1A2 and CYP2E1 in an intact animal model, a double-null mouse line lacking
      functional expression of CYP1A2 and CYP2E1 was produced by cross-breeding Cyp1a2
      /- mice with Cyp2e1-/- mice. Animals deficient in the expression of both P450s
      developed normally and exhibited no obvious phenotypic abnormalities. Comparison
      of the dose-response to APAP (200-1200 mg/kg) indicated that double-null animals
      were highly resistant to APAP-induced toxicity whereas the wild-type animals were
      sensitive. Administration of 600 to 800 mg/kg of this drug to male wild-type
      animals resulted in increased plasma concentrations of liver enzymes (alanine
      aminotransferase, sorbitol dehydrogenase), lipidosis, hepatic necrosis, and renal
      tubular necrosis. In contrast, when APAP of equivalent or higher dose was
      administered to the double-null mice, plasma levels of liver enzymes and liver
      histopathology were normal. However, administration of 1200 mg of APAP/kg to the
      double-null mice resulted in infrequent liver lipidosis and mild kidney lesions.
      Consistent with the protection from hepatotoxicity, the expected depletion of
      hepatic glutathione (GSH) content was significantly retarded and APAP covalent
      binding to hepatic cytosolic proteins was not detectable in the double-null mice.
      Likewise, in vitro activation of APAP by liver microsomes from the double-null
      mice was approximately one tenth of that in microsomes from wild-type mice. Thus,
      the protection against APAP toxicity afforded by deletion of both CYP2E1 and
      CYP1A2 likely reflects greatly diminished production of the toxic electrophile,
      NAPQI.

PMID- 9772216
TI  - Characterization of 2,3,7,8-tetrachlorodibenzofuran-dependent suppression and AH
      receptor pathway gene expression in the developing mouse mammary gland.
AB  - The AH receptor (AHR) is a ligand-activated transcription factor and member of a
      growing family of homologous proteins implicated in development. In this study we
      have characterized the actions of 2,3, 7,8-tetrachlorodibenzofuran (TCDF), a well
      studied AHR ligand, and the expression of AHR and selected AHR signal
      transduction pathway genes in the developing mouse mammary gland. High levels of
      AHR protein were observed in the mammary glands of C57Bl/6J (AHR +/+) mice during
      estrous-stimulated growth and branching of terminal end buds (TEBs). Comparative
      analysis of mammary gland development in AHR -/- and +/+ littermates revealed a
      50% reduction in TEBs and an increase in blunt-ended terminal ducts in the AHR
      null animals. Treatment of mammary glands, removed from estrogen/progesterone
      primed C57Bl/6J mice and maintained in organ culture, with TCDF suppressed lobule
      development (greater than twofold decreases in lobule number and size), with a
      concomitant suppression of DNA synthesis, as judged by a 35 to 45% decrease in
      [3H]thymidine incorporation in the TEBs. Immunohistochemical staining patterns
      for AHR, aryl hydrocarbon nuclear translocator (ARNT; the heterodimerization
      partner of AHR), and two AHR-regulated genes, Cyp1A1 and Cyp1B1, were similar and
      not altered by treatment of mammary glands in organ culture with TCDF. The
      observed differences in the development of mammary glands from AHR +/+ and -/-
      mice, associated expression of the AHR protein with hormone-dependent lobule
      development, and suppressive actions of TCDF support the position that, in
      C57Bl/6J mice, development of the mammary gland is at least in part AHR
      dependent. Development occurs in the absence of exogenous AHR ligand, suggesting
      that the unoccupied receptor may function to support the proliferative stages
      required for full lobule development.

PMID- 9772217
TI  - Application of a hybrid computational fluid dynamics and physiologically based
      inhalation model for interspecies dosimetry extrapolation of acidic vapors in the
      upper airways.
AB  - This study provides a scientific basis for interspecies extrapolation of nasal
      olfactory irritants from rodents to humans. By using a series of short-term in
      vivo studies, in vitro studies with nasal explants, and computer modeling,
      regional nasal tissue dose estimates were made and comparisons of tissue doses
      between species were conducted. To make these comparisons, this study assumes
      that human and rodent olfactory epithelium have similar susceptibility to the
      cytotoxic effects of organic acids based on similar histological structure and
      common mode of action considerations. Interspecies differences in susceptibility
      to the toxic effects of acidic vapors are therefore assumed to be driven
      primarily by differences in nasal tissue concentrations that result from regional
      differences in nasal air flow patterns relative to the species-specific
      distribution of olfactory epithelium in the nasal cavity. The acute, subchronic,
      and in vitro studies have demonstrated that the nasal olfactory epithelium is the
      most sensitive tissue to the effects of inhalation exposure to organic acids and
      that the sustentacular cells are the most sensitive cell type of this epithelium.
      A hybrid computational fluid dynamics (CFD) and physiologically based
      pharmacokinetic (PBPK) dosimetry model was constructed to estimate the regional
      tissue dose of organic acids in the rodent and human nasal cavity. The CFD-PBPK
      model simulations indicate that the olfactory epithelium of the human nasal
      cavity is exposed to two- to threefold lower tissue concentrations of a
      representative inhaled organic acid vapor, acrylic acid, than the olfactory
      epithelium of the rodent nasal cavity when the exposure conditions are the same.
      The magnitude of this difference varies somewhat with the specific exposure
      scenario that is simulated. The increased olfactory tissue dose in rats relative
      to humans may be attributed to the large rodent olfactory surface area (greater
      than 50% of the nasal cavity) and its highly susceptible location (particularly,
      a projection of olfactory epithelium extending anteriorly in the dorsal meatus
      region). In contrast, human olfactory epithelium occupies a much smaller surface
      area (less than 5% of the nasal cavity), and it is in a much less accessible
      dorsal posterior location. In addition, CFD simulations indicate that human
      olfactory epithelium is poorly ventilated relative to rodent olfactory
      epithelium. These studies suggest that the human olfactory epithelium is
      protected from irritating acidic vapors significantly better than rat olfactory
      epithelium due to substantive differences in nasal anatomy and nasal air flow.
      Furthermore, the general structure of the hybrid CFD-PBPK model used for this
      study appears to be useful for target tissue dosimetry and interspecies dose
      comparisons for a wide range of inhaled vapors.

PMID- 9772218
TI  - Distribution and induction of cytochrome P450 1A1 and 1A2 in rat brain.
AB  - Cytochromes P450 1A1 and 1A2 are involved in the oxidation of a wide spectrum of
      endogenous compounds and xenobiotics. Although their presence has been repeatedly
      confirmed in brain tissue, reports regarding their distribution in the brain are
      often contradictory. In the present study the possibility was examined that
      CYP1A1 and CYP1A2 are localized and inducible in the brain-CSF barrier and
      regions with a leaky blood brain barrier, where they may serve as a protective
      metabolic barrier. CYP1A1 and CYP1A2 levels were determined in subcellular
      fractions of multiple brain regions, as well as tissue homogenates of
      circumventricular organs, and the meninges by Western blotting and catalytic
      activity in control male rats and rats treated with the inducer beta
      naphthoflavone (BNF). In control animals CYP1A1 immunoreactive protein was
      undetectable in regional brain microsomes or whole tissue homogenates of the
      arachnoid, dura mater, choroid plexus, pineal gland, median eminence, and
      pituitary. However, low levels of ethoxyresorufin O-deethylase (EROD) activity
      were observed in homogenates of the arachnoid, dura mater, choroid plexus, pineal
      gland, and pituitary. Western blotting revealed only low levels of CYP1A2
      immunoreactive protein in brain microsomes from the cortex, cerebellum,
      brainstem, thalamus, hippocampus, and striatum from control animals. Following
      BNF treatment, EROD activity was induced 12-42-fold in the arachnoid, choroid
      plexus, dura mater, pineal gland, pituitary, and median eminence. Western blot
      analysis revealed CYP1A1 to be induced in the arachnoid, dura mater, choroid
      plexus, pineal gland, and pituitary, while CYP1A2 was undetectable. No induction
      of CYP1A1 or CYP1A2 protein was observed in brain microsomes from the olfactory
      bulb, cortex, striatum, hippocampus, cerebellum, or brainstem following BNF
      treatment, providing that the arachnoid membranes and choroid plexus had been
      carefully removed prior to brain dissection. Neither CYP1A1, 1A2 protein, nor
      EROD activity were detected in purified brain mitochondria, regardless of
      treatment or region. In conclusion, catalytically active CYP1A1 is located in the
      meninges as well as certain circumventricular organs, is inducible by BNF, and
      appears to be absent or expressed constitutively at very low levels in the
      majority of the brain parenchyma. The localization of CYP1A1 in the blood-CSF
      barrier and circumventricular tissues likely plays a role in protecting the brain
      from xenobiotics.

PMID- 9772219
TI  - Inhibition of transforming growth factor-beta1 and UV light-induced apoptosis by
      prostanoids in primary cultures of rat hepatocytes.
AB  - Treatment of rat hepatocytes cultured in collagen gel with transforming growth
      factor-beta1 (TGFbeta1) or with UV light strongly increased the frequency of
      apoptotic nuclei within 24 h; at doses of 0.5 ng/ml TGFbeta1 or 90 J/m2 UV light
      about 17 and 22% apoptotic nuclei were determined, respectively. DNA of the
      treated cells showed internucleosomal DNA fragmentation. Already the presence of
      the cytokine for only 1 h significantly induced apoptosis. The prostanoids PGI2,
      PGD2, and PGE1 decreased the frequency of apoptotic nuclei in a dose-dependent
      manner by up to 70 to 80% and suppressed internucleosomal DNA fragmentation. In
      contrast, PGE2 and PGF2alpha elicited a smaller protective effect and arachidonic
      acid had none. In the case of PGE1 it was shown that the prostaglandin was most
      effective when added together with TGFbeta1 or within 2 h before or after
      treatment with this cytokine. An early increase of the tumor suppressor gene
      product p53 is thought to play a decisive role in UV light-induced apoptosis.
      However, this increase in p53 was not affected by the strong cytoprotective
      prostacyclin PGI2. Our findings show a marked antiapoptotic activity of the
      prostanoids PGE1, PGI2, and PGD2 and raise the question of whether these
      prostanoids may influence apoptosis in pathological processes in the liver.

PMID- 9772221
TI  - Effects of gastrointestinal prokinetic agents, TKS159 and cisapride, on the in
      situ canine heart assessed by cardiohemodynamic and electrophysiological
      monitoring.
AB  - Effects of a novel 5-HT4 receptor agonist TKS159 on the cardiovascular system
      were assessed in comparison with cisapride using an in vivo canine model. TKS159
      in doses of 0.1, 1.0, and 10 mg/kg (n = 6) or cisapride in 1/10 doses of 0.01,
      0.1, and 1.0 mg/kg (n = 6) was cumulatively infused over 10 min with a pause of
      20 min. The doses of the drugs were determined according to the previous
      knowledge of their pharmacokinetics. Clinically effective plasma concentrations
      as a gastrointestinal prokinetic drug were obtained after the infusion of 0.1
      mg/kg of the respective drugs. In TKS159-administered animals, no significant
      change was induced in each cardiovascular parameter by an infusion of 0.1 mg/kg.
      The blood pressure was decreased, and the effective refractory period and
      repolarization phase of the ventricle were prolonged after 1.0 mg/kg. The heart
      rate was decreased, and the atrioventricular, as well as intraventricular,
      conduction were suppressed after 10 mg/kg, while no significant changes were
      observed in the cardiac output and the ventricular contraction and the relative
      refractory period of the ventricle during the study. Meanwhile, in cisapride
      administered animals, the repolarization phase and the effective refractory
      period were prolonged after 0.01 mg/kg. The heart rate and the blood pressure
      were decreased after 0.1 mg/kg. The cardiac output, the ventricular contraction,
      and the atrioventricular conduction were suppressed, the relative refractory
      period was prolonged, and early afterdepolarization was detected after 1.0 mg/kg,
      while no significant change was observed in the intraventricular conduction
      during the study. Thus, TKS159 may have a safer cardiovascular profile than
      cisapride.

PMID- 9772220
TI  - Nonresponsiveness to 2,3,7,8-tetrachlorodibenzo-p-dioxin of transforming growth
      factor beta1 and CYP 1A1 gene expression in rat liver fat-storing cells.
AB  - Exposure to the potent tumor promoter 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD)
      or related agonists of the aryl hydrocarbon receptor (AhR) can result in
      hepatocarcinogenesis in rodents. Changes in the expression and/or the level of
      growth factors may be a critical event in TCDD-mediated hepatocarcinogenesis. In
      this study, the influence of TCDD, the most potent AhR agonist, on the expression
      of transforming growth factor beta1 (TGF beta1), an inhibitor of hepatocellular
      proliferation synthesized in fat-storing cells (FSC) of the liver, was
      investigated in Wistar rats of both sexes in vitro and ex vivo. FSC were isolated
      from rat liver, cultured, and treated with 10(-10) and 10(-8) M TCDD,
      respectively, and TGF beta1 gene expression was determined at the levels of mRNA
      and protein. Furthermore, adult rats were treated with TCDD (10 micrograms/kg
      body wt, given by a single ip injection), FSC were isolated, and TGF beta1 gene
      expression was analyzed at different time points. Exposure to TCDD had no effect
      on the expression of TGF beta1 either at the RNA or at the protein level.
      Surprisingly, expression of CYP1A1, an AhR-regulated gene, was also not
      detectable either in untreated FSC or after TCDD treatment in vitro or ex vivo.
      Western blot analysis revealed that the lack of TCDD responsiveness of CYP1A1 is
      due to the absence of detectable amounts of the AhR in FSC. Based on these
      results we conclude that FCS may be the only liver cell type that lacks AhR
      dependent inducibility of drug metabolism.

PMID- 9772222
TI  - Hepatobiliary effects of tertiary-butylhydroperoxide (tBOOH) in isolated rat
      hepatocyte couplets.
AB  - The organic hydroperoxide, tertiary-butylhydroperoxide (tBOOH), causes oxidative
      damage in a number of cell types. It is used here in an isolated rat hepatocyte
      couplet preparation to study adverse hepatobiliary effects of peroxidative damage
      in vitro. At subcytotoxic concentrations (as determined by lactate dehydrogenase
      release and maintenance of cytoplasmic ATP concentrations) tBOOH caused decreased
      accumulation of a fluorescent bile acid analogue, cholyl-lysyl-fluorescein (CLF),
      in the canalicular vacuole of couplets (a hepatobiliary effect; cholestasis).
      This was dose dependent in the range 100-200 microM. At the same concentrations
      it brought about release of preaccumulated CLF, suggesting that its effect was
      more likely to be on sealing properties of the vacuole than processes of uptake,
      transcytosis, and secretion. Pretreatment of tBOOH-treated couplets with the
      antioxidants deferoxamine mesylate (iron chelator) and dimethyl sulfoxide (free
      radical scavenger) resulted in the prevention of both canalicular vacuolar
      accumulation (cVA, which assesses canalicular function) and canalicular vacuolar
      retention (cVR, which assesses the retaining ability of couplets) depression at
      100 microM tBOOH but not at higher concentrations. This indicates that the
      cholestatic effect of tBOOH has a preventable and nonpreventable phase and that
      free radicals are involved in these processes. By selectively generating the two
      types of tBOOH radical, peroxyl (tBOO.) and alkoxyl (tBO.), using suitable
      catalysts, we were able to determine that the peroxyl radical was most probably
      involved in tBOOH-induced cholestasis. This was further supported by experiments
      employing specific peroxyl and alkoxyl radical scavengers; only the peroxyl
      scavenger reduced the effect of tBOOH upon canalicular function under the
      conditions studied.

PMID- 9772223
TI  - A genetic polymorphism in the regulatory sequences of human CYP2E1: association
      with increased chlorzoxazone hydroxylation in the presence of obesity and ethanol
      intake.
AB  - To pursue the hypothesis that differences in the regulatory region of CYP2E1 are
      partially responsible for the intersubject variation in in vivo CYP2E1 activity,
      restriction enzyme digestion and Southern blotting of 36 human DNA samples were
      performed. The fractionated DNA was hybridized with a genomic probe to the
      upstream region of CYP2E1 from positions -2710 to -580. After digestion with the
      restriction enzyme XbaI, most subjects (69%) were homozygous for the expected
      band representing the XbaI fragment from positions -2270 to -408, whereas 31% had
      an unexpected, slightly larger band. Analyses of Southern blots of the same DNA
      samples cut by other restriction enzymes were consistent with the larger band
      containing an estimated 100-bp insertion and localized the mutation to a region
      from positions -2270 to -1672. To determine the functional significance of this
      mutation, in vivo CYP2E1 metabolic ability was determined in the same subjects
      using the 6-hydroxylation of chlorzoxazone as a probe. The presence of the
      insertion mutation was associated with greater CYP2E1 metabolic ability, but only
      among individuals who either were obese or had recently consumed ethanol (p <
      0.01, both). These data are consistent with a DNA insertion that is associated
      with altered CYP2E1 induction. The incidence of the mutation was 31% among 65
      African Americans and 6.9% among 58 Caucasians (p < 0.01). Thus, this CYP2E1
      regulatory polymorphism not only enhances CYP2E1 metabolic ability, but is
      sufficiently common to impact susceptibility to CYP2E1-related diseases in at
      least two ethnic groups.

PMID- 9772224
TI  - Characterization of an ochratoxin-A-dedifferentiated and cloned renal epithelial
      cell line.
AB  - Ochratoxin A (OTA) is a ubiquitous fungal metabolite with predominant nephrotoxic
      action. OTA impairs postproximal renal electrolyte handling and increases the
      incidence of renal adenoma and carcinoma. Furthermore, it is supposed to be
      involved in the pathogenesis of different forms of human renal diseases.
      Previously we have shown that OTA activates extracellular signal-regulated kinase
      1 (ERK1) and ERK2 in the C7 clone but not in the C11 clone of renal epithelial
      MDCK cells. Here we show that nanomolar concentrations of OTA lead to stable and
      irreversible phenotypical and genotypical alterations, resulting in sustained
      dedifferentiation of MDCK-C7 cells but not of MDCK-C11 cells. Dedifferentiated
      MDCK-C7 cells (OTA-C7 cells) display a distinct morphology from the parent cell
      line (spindle-shape, pleiomorphic, narrow intercellular spaces, increased cell
      size) and show a reduced proliferation rate and numerical chromosomal
      aberrations. Functionally, OTA-C7 cells are characterized by a dramatic reduction
      of transepithelial electrolyte transport and the complete loss of responsiveness
      to the mineralocorticoid hormone aldosterone. Our data provide further evidence
      that OTA can lead to cell dedifferentiation and eventually to transformation of
      cloned quiescent cells. The changes in phenotype due to this dedifferentiation
      could explain some of the OTA-induced changes in renal function.

PMID- 9772225
TI  - Effect of a serotonergic extrinsic modulatory neuron (MCC) on radula
      mechanoafferent function in Aplysia.
AB  - The serotonergic metacerebral cells (MCCs) and homologous neurons in related
      mollusks have been extensively investigated within the context of feeding.
      Although previous work has indicated that the MCCs exert widespread actions, MCC
      modulation of sensory neurons has not been identified. We characterized
      interactions between the MCCs and a cell that is part of a recently described
      group of buccal radula mechanoafferents. The cell, B21, has a peripheral process
      in the tissue underlying the chitinous radula [the subradula tissue (SRT)].
      Previous studies have shown that B21 can fire phasically during ingestive motor
      programs and provide excitatory drive to the circuitry active during radula
      closing/retraction. We now show that activity of B21 can be modulated by
      serotonin (5-HT) and the MCCs. Centrally, although a slow depolarization is
      typically recorded in B21 as a result of MCC stimulation, this depolarization
      does not cause B21 to spike. It can, however, increase B21 excitability enabling
      a pulse that was previously subthreshold to elicit an action potential in B21.
      B21 is in fact rhythmically depolarized during the radula closing/retraction
      phase of ingestive motor programs. Thus central effects of the MCCs on radula
      mechanoafferent activity are only likely to be apparent while B21 is receiving
      input from the feeding central pattern generator. Peripherally, radula
      mechanoafferent neurons can be activated 1) when a mechanical stimulus is applied
      to the biting surface of the SRT and 2) when the SRT contracts. MCC stimulation
      and 5-HT modulate B21 responses to both types of stimuli. For example, MCC
      stimulation and low concentrations of 5-HT cause subthreshold mechanical stimuli
      applied to the SRT to become suprathreshold. 5-HT and MCC stimulation also
      enhance SRT contractility. Peripheral effects of MCC activity are also likely to
      be phase dependent. For example, MCC stimulation does not cause B21 to respond to
      peripheral stimuli with an afterdischarge. Consequently, radula mechanoafferents
      are likely to be activated when food is present between the radula halves during
      radula closing/retraction but are not likely to continue to fire as
      opening/protraction is initiated. In a similar vein, MCC effects on the
      contractility of the SRT will only be apparent when contractions are elicited by
      motor neuron activity. SRT motor neurons are rhythmically activated during
      ingestive motor programs. Thus we have shown that radula mechanoafferent activity
      can be modulated by the MCCs and that this modulation is likely to occur in a
      phase-dependent manner.

PMID- 9772227
TI  - Physiological survey of medullary raphe and magnocellular reticular neurons in
      the anesthetized rat.
AB  - The present study was designed to provide a detailed and quantitative description
      of the physiological characteristics of neurons in the medullary raphe magnus
      (RM) and adjacent nucleus reticularis magnocellularis (NRMC) under anesthetized
      conditions. The background discharge and noxious stimulus-evoked responses of RM
      and NRMC neurons were recorded in rats lightly anesthetized with isoflurane. All
      cells that were isolated successfully were studied. After recording background
      discharge, the neuronal response to repeated noxious thermal and noxious
      mechanical stimulation of the tail was recorded. Most cells were identified as
      nonserotonergic by their irregular or rapid background discharge pattern. Because
      the spontaneous discharge of most RM nonserotonergic cells contained pauses and
      bursts, a comparison between the change in rate evoked by tail heat and the range
      of rate changes that occur spontaneously was used to classify cells. The mean
      responses of ON and OFF cells were more than four times the standard deviation of
      the changes in rate observed spontaneously. ON cells were excited in 86% of the
      tail heat trials tested. Similarly, OFF cells were inhibited in 97% of the
      noxious tail heat trials tested. The heat-evoked changes in ON and OFF cell
      discharge varied over more than two orders of magnitude and were greater in cells
      with greater rates of background discharge. The heat-evoked responses of and
      cells had durations of tens of seconds to minutes and were always sustained
      beyond the visible motor response. Most ON and OFF cells responded to noxious
      tail clamp in a manner that was similar to their response to noxious heat. More
      than half of the NEUTRAL cells that were unresponsive to noxious heat were
      responsive to noxious tail clamp. A minority of ON, OFF, and NEUTRAL cells
      responded to innocuous brush stimulation with weak, transient responses. Although
      many cells discharged too infrequently to be classified, units with physiological
      properties that were different from those described above were rare. In
      conclusion, most RM and NRMC cells belong to three nonserotonergic physiological
      cell classes that can be distinguished from each other by the consistency, not
      the magnitude, of their responses to repeated noxious thermal stimulation.
      Because most of the heat-evoked change in and cell discharge occurs after the
      conclusion of the initial motor withdrawal, ON and OFF cells are likely to
      principally modulate the response to subsequent noxious insults.

PMID- 9772226
TI  - Duration of NMDA-dependent synaptic potentiation in piriform cortex in vivo is
      increased after epileptiform bursting.
AB  - Stimulation of afferent fibers with current pulse trains has been reported to
      induce long-term potentiation (LTP) in piriform cortex in vitro but not in vivo.
      LTP has been observed in vivo only when trains are paired with behavioral
      reinforcement and as a consequence of kindled epileptogenesis. This study was
      undertaken in the urethan-anesthetized rat to determine if the reported failures
      to observe pulse-train evoked LTP in vivo may be related to a lesser persistence
      rather than lack of occurrence, if disinhibition might facilitate induction, and
      to examine the nature of the relationship between seizure activity and LTP.
      Stimulation of afferent fibers in the lateral olfactory tract with theta-burst
      trains under control conditions potentiated the monosynaptic field excitatory
      postsynaptic potential (EPSP) by approximately the same extent (20.3 +/- 2%; n =
      12) as reported for the slice. However, in contrast to the slice, potentiation in
      vivo decayed to a low level within 1-2 h after induction (70% loss in 1.5 h, on
      average). The N-methyl--aspartate (NMDA)-receptor antagonists -APV and MK-801
      blocked the induction of this decremental potentiation. Pharmacological reduction
      of gamma-aminobutyric acid-mediated inhibition at the recording site did not
      increase the duration of potentiation. In contrast, theta-burst stimulation
      applied after recovery from a period of epileptiform bursting induced stable NMDA
      dependent potentiation. Mean increase in the population EPSP was approximately
      the same as under control conditions (21 +/- 2%; n = 6), but in five of six
      experiments there was little or no decay in potentiation for the duration of the
      monitoring period (</=6 h). It is concluded that seizure activity has an enabling
      action on the induction of persistent synaptic potentiation by stimulus trains
      that bypasses the need for behavioral reinforcement.

PMID- 9772228
TI  - Modulation of voltage-activated calcium currents by mechanical stimulation in rat
      sensory neurons.
AB  - We examined the effects of mechanical stress, induced by a stream of bath
      solution, on evoked action potentials, electrical excitability, and Ca2+ currents
      in rat dorsal root ganglion neurons in culture with the use of the whole cell
      patch-clamp technique. Action-potential duration was altered reversibly by flow
      in 39% of the 51 neurons tested, but membrane potential and excitability were
      unaffected. The flow-induced increases and decreases in action-potential duration
      were consistent with the different effects of flow on two types of Ca2+ channel,
      determined by voltage-clamp recordings of Ba2+ currents. Current through omega
      conotoxin-sensitive (N-type) Ca2+ channels increased by an estimated 74% with
      flow, corresponding to 23% increase in the total high voltage-activated current,
      whereas current through low-threshold voltage-activated (T-type) channels
      decreased by 14%. We conclude that modulation of voltage-activated Ca2+ currents
      constitutes a route by which mechanical events can regulate Ca2+ influx in
      sensory neurons.

PMID- 9772229
TI  - Morphological and membrane properties of rat magnocellular basal forebrain
      neurons maintained in culture.
AB  - Morphological and electrophysiological characteristics of magnocellular neurons
      from basal forebrain nuclei of postnatal rats (11-14 days old) were examined in
      dissociated cell culture. Neurons were maintained in culture for periods of 5-27
      days, and 95% of magnocellular (>23 micron diam) neurons stained positive with
      acetylcholinesterase histochemistry. With the use of phase contrast microscopy,
      four morphological subtypes of magnocellular neurons could be distinguished
      according to the shape of their soma and pattern of dendritic branching.
      Corresponding passive and active membrane properties were investigated with the
      use of whole cell configuration of the patch-clamp technique. Neurons of all cell
      types displayed a prominent (6-39 mV; 6.7-50 ms duration) spike
      afterdepolarization (ADP), which in some cells reached firing threshold. The ADP
      was voltage dependent, increasing in amplitude and decreasing in duration with
      membrane hyperpolarization with an apparent reversal potential of -59 +/- 2.3
      (SE) mV. Elevating [Ca2+]o (2.5-5.0 mM) or prolonging spike repolarization with
      10 mM tetraethylammonium (TEA) or 1 mM 4-aminopyridine (4-AP), potentiated the
      ADP while it was inhibited by reducing [Ca2+]o (2.5-1 mM) or superfusion with
      Cd2+ (100 microM). The ADP was selectively inhibited by amiloride (0.1-0.3 mM or
      Ni2+ 10 microM) but unaffected by nifedipine (3 microM), omega-conotoxin GVIA
      (100 nM) or omega-agatoxin IVA (200 nM), indicating that Ca2+ entry was through T
      type Ca2+ channels. After inhibition of the ADP with amiloride (300 microM),
      depolarization to less than -65 mV revealed a spike afterhyperpolarization (AHP)
      with both fast and slow components that could be inhibited by 4-AP (1 mM) and
      Cd2+ (100 microM), respectively. In all cell types, current-voltage relationships
      exhibited inward rectification at hyperpolarized potentials >/=EK (approximately 
      90 mV). Application of Cs+ (0.1-1 mM) or Ba2+ (1-10 microM) selectively inhibited
      inward rectification but had no effect on resting potential or cell excitability.
      At higher concentrations, Ba2+ (>10 microM) also inhibited an outward current
      tonically active at resting potential (VH -70 mV), which under current-clamp
      conditions resulted in small membrane depolarization (3-10 mV) and an increase in
      cell excitability. Depolarizing voltage commands from prepulse potential of -90
      mV (VH -70 mV) in the presence of tetrodotoxin (0.5 microM) and Cd2+ (100 microM)
      to potentials between -40 and +40 mV cause voltage activation of both transient A
      type and sustained delayed rectifier-type outward currents, which could be
      selectively inhibited by 4-AP (0.3-3 mM) and TEA (1-3 mM), respectively. These
      results show that, although acetylcholinesterase-positive magnocellular basal
      forebrain neurons exhibit considerable morphological heterogeneity, they have
      very similar and characteristic electrophysiological properties.

PMID- 9772230
TI  - Zinc and zolpidem modulate mIPSCs in rat neocortical pyramidal neurons.
AB  - Pharmacological modulation of gamma-aminobutyric acid-A (GABAA) receptors can
      provide important information on the types of subunits composing these receptors.
      In recombinant studies, zinc more potently inhibits alphabeta subunits compared
      with the alphabetagamma combination, whereas modulation by nanomolar
      concentrations of the benzodiazepine type 1-selective agonist zolpidem is
      conferred by the alpha1betagamma2 subunit combination. We examined four
      properties of miniature inhibitory postsynaptic currents (mIPSCs) from identified
      necortical pyramidal cells in rat brain slices: decay time constant, peak
      amplitude, rate of rise, and interevent interval. Exposure to 50 microM zinc
      reduced the decay time constant, peak amplitude, and rate of rise with no effect
      on interevent interval. Zolpidem enhanced mIPSCs in a concentration-dependent
      manner. Both 20 and 100 nM zolpidem increased the decay time constants of mIPSCs.
      In some cells, both peak amplitude and rate of rise were also enhanced. All cells
      treated with zinc were also responsive to zolpidem. These results show that
      neocortical pyramidal cells have a population of GABAA receptors sensitive to
      both zinc and zolpidem.

PMID- 9772231
TI  - State-dependent nickel block of a high-voltage-activated neuronal calcium
      channel.
AB  - Effect of nickel ions (Ni2+) on noninactivating calcium channels in squid giant
      fiber lobe (GFL) neurons were investigated with whole cell voltage clamp. Three
      different effects of Ni2+ were observed to be associated with distinct Ca2+
      channel activation states. 1) Nickel ions appear to stabilize closed channel
      states and, as a result, slow activation kinetics. 2) Nickel ions block open
      channels with little voltage dependence over a wide range of potentials. 3) Block
      of open channels by Ni2+ becomes more effective during an extended strong
      depolarization, and this effect is voltage dependent. Recovery from this
      additional inhibition occurs at intermediate voltages, consistent with the
      presence of two distinct types of Ni2+ block that we propose correspond to two
      previously identified open states of the calcium channel. These results, taken
      together with earlier evidence of state-dependent block by omega-agatoxin IVA,
      suggest that Ni2+ generates these unique effects in part by interacting
      differently with the external surface of the GFL calcium channel complex in ways
      that depend on channel activation state.

PMID- 9772232
TI  - Analysis of the role of inhibition in shaping responses to sinusoidally amplitude
      modulated signals in the inferior colliculus.
AB  - Neurons in the central nucleus of the inferior colliculus (ICc) typically respond
      with phase-locked discharges to low rates of sinusoidal amplitude-modulated (SAM)
      signals and fail to phase-lock to higher SAM rates. Previous studies have shown
      that comparable phase-locking to SAM occurs in the dorsal nucleus of the lateral
      lemniscus (DNLL) and medial superior olive (MSO) of the mustache bat. The studies
      of MSO and DNLL also showed that the restricted phase-locking to low SAM rates is
      created by the coincidence of phase-locked excitatory and inhibitory inputs that
      have slightly different latencies. Here we tested the hypothesis that responses
      to SAM in the mustache bat IC are shaped by the same mechanism that shapes
      responses to SAM in the two lower nuclei. We recorded responses from ICc neurons
      evoked by SAM signals before and during the iontophoretic application of several
      pharmacological agents: bicuculline, a competitive antagonist for gamma
      aminobutyric acid-A (GABAA) receptors; strychnine, a competitive antagonist for
      glycine receptors; the GABAB receptor blocker, phaclofen, and the N-methyl-D
      aspartate (NMDA) receptor blocker, (-)-2-amino-5-phosphonopentanoic acid (AP5).
      The hypothesis that inhibition shapes responses to SAM signals in the ICc was not
      confirmed. In >90% of the ICc neurons tested, the range of SAM rates to which
      they phase-locked was unchanged after blocking inhibition with bicuculline,
      strychnine or phaclofen, applied either individually or in combination. We also
      considered the possibility that faster alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid (AMPA) receptors follow high temporal rates of incoming excitation
      but that the slower NMDA receptors could follow only lower rates. Thus at higher
      SAM rates, NMDA receptors might generate a sustained excitation that "smears" the
      phase-locked excitation generated by the AMPA receptors. The NMDA hypothesis,
      like the inhibition hypothesis, was also not confirmed. In none of the cells that
      we tested did the application of AP5 by itself, or in combination with
      bicuculline, cause an increase in the range of SAM rates that evoked phase
      locking. These results illustrate that the same response property, phase-locking
      restricted to low SAM rates, is formed in more than one way in the auditory brain
      stem. In the MSO and DNLL, the mechanism is coincidence of phase-locked
      excitation and inhibition, whereas in ICc the same response feature is formed by
      a different but unknown mechanism.

PMID- 9772233
TI  - Intracellular pH buffering shapes activity-dependent Ca2+ dynamics in dendrites
      of CA1 interneurons.
AB  - Voltage-gated calcium (Ca) channels are highly sensitive to cytosolic H+, and
      Ca2+ influx through these channels triggers an activity-dependent fall in
      intracellular pH (pHi). In principle, this acidosis could act as a negative
      feedback signal that restricts excessive Ca2+ influx. To examine this
      possibility, whole cell current-clamp recordings were taken from rat hippocampal
      interneurons, and dendritic Ca2+ transients were monitored fluorometrically
      during spike trains evoked by brief depolarizing pulses. In cells dialyzed with
      elevated internal pH buffering (high beta), trains of >15 action potentials (Aps)
      provoked a significantly larger Ca2+ transient. Voltage-clamp analysis of whole
      cell Ca currents revealed that differences in cytosolic pH buffering per se did
      not alter baseline Ca channel function, although deliberate internal
      acidification by 0.3 pH units blunted Ca currents by approximately 20%. APs
      always broadened during a spike train, yet this broadening was significantly
      greater in high beta cells during rapid but not slow firing rates. This effect of
      internal beta on spike repolarization could be blocked by cadmium. High beta also
      1) enhanced the slow afterhyperpolarization (sAHP) seen after a spike train and
      2) accelerated the decay of an early component of the sAHP that closely matched a
      sAHP conductance that could be blocked by apamin. Both of these effects on the
      sAHP could be detected at high but not low firing rates. These data suggest that
      activity-dependent pHi shifts can blunt voltage-gated Ca2+ influx and retard
      submembrane Ca2+ clearance, suggesting a novel feedback mechanism by which Ca2+
      signals are shaped and coupled to the level of cell activity.

PMID- 9772234
TI  - Electrical microstimulation distinguishes distinct saccade-related areas in the
      posterior parietal cortex.
AB  - Electrical microstimulation (0.1-ms bipolar pulses at 500 Hz, current strength
      usually between 100 and 200 microA) was used to delineate saccade-related areas
      in the posterior parietal cortex of monkeys. Stimulation-induced saccades were
      found to be restricted to the lateral intraparietal area (area LIP) in the
      intraparietal sulcus (IPS) and a region on the medial aspect of the parietal lobe
      (area MP, medial parietal area), close to the caudal end of the cingulate sulcus,
      whereas stimulation of area 7a did not evoke eye movements. Two different types
      of evoked saccades were observed. Modified vector saccades, whose amplitude was
      modified by the position of the eyes at stimulation onset were the hallmark of
      sites in area LIP and area MP. The same sites were characterized by a propensity
      of single units active in the memory and presaccadic response segments of the
      memory saccade paradigm. Goal-directed saccades driving the eyes toward a
      circumscribed region relative to the head were largely restricted to a small
      strip of cortex on the lateral bank and the floor of the IPS (the intercalated
      zone), separating the representation of upward and downward directed saccades in
      LIP. Unlike stimulation in LIP or MP, stimulation in the intercalated zone gave
      rise to head, pinnae, facial, and shoulder movements accompanying the evoked
      saccades. We propose that the amplitude modification of vector saccades
      characterizing LIP and MP may reflect a spatially distributed head-centered
      coding scheme for saccades. On the other hand, the goal-directed saccades found
      in the intercalated zone could indicate the use of a spatially much more
      localized representation of desired location in head-centered space.

PMID- 9772235
TI  - Long-range connections synchronize rather than spread intrathalamic oscillations:
      computational modeling and in vitro electrophysiology.
AB  - A thalamic network model was developed based on recent data regarding
      heterogeneous thalamic reticular (RE) cell axonal arborizations that indicate at
      least two projection patterns, short-range cluster projections and long-range
      diffuse projections. The model was constrained based on expected convergence and
      the biophysical properties of RE and thalamocortical (TC) cells and their
      synapses. The model reproduced in vitro synchronous slow (3-Hz) oscillatory
      activity and the known effects of T-channel blockade and cholecystokinin (CCK)
      application on this activity. Whereas previous models used the speed at which
      approximately 3-Hz oscillations propagate in vitro to infer the spatial extent of
      intrathalamic projections, we found that, so long as the gamma-aminobutyric acid
      B synaptic conductance was adjusted appropriately, a network with only short
      range projections and another network with both short- and long-range projections
      could both produce physiologically realistic propagation speeds. Although the
      approximately 3-Hz oscillations propagated at similar speeds in both networks,
      phase differences between oscillatory activity at different locations in the
      network were much smaller in the network containing both short- and long-range
      projections. We measured phase differences in vitro and found that they were
      similar to those that arise in the network containing both short- and long-range
      projections but are inconsistent with the much larger phase differences that
      occur in the network containing only short-range projections. These results
      suggest that, although they extend much further than do short-range cluster
      projections, long-range diffuse projections do not spread activity over greater
      distances or increase the speed at which intrathalamic oscillations propagate.
      Instead, diffuse projections may function to synchronize activity and minimize
      phase shifts across thalamic networks. One prediction of this hypothesis is that,
      immediately after a collision between propagating oscillations, phase gradients
      should vary smoothly across the thalamic slice. The model also predicts that
      phase shifts between oscillatory activity at different points along a thalamic
      slice should be unaffected by T-channel blockers and decreased by suppression of
      synaptic transmission or application of CCK.

PMID- 9772236
TI  - Characterization of spontaneous inhibitory synaptic currents in salamander
      retinal ganglion cells.
AB  - Spontaneous and light-evoked postsynaptic currents (sPSCs and lePSCs,
      respectively) in retinal ganglion cells of the larval tiger salamander were
      recorded under voltage-clamp conditions from living retinal slices. The focus of
      this study is to characterize the spontaneous inhibitory PSCs (sIPSCs) and their
      contribution to the light-evoked inhibitory PSCs (leIPSCs) in ON-OFF ganglion
      cells. sIPSCs were isolated from spontaneous excitatory PSCs (sEPSCs) by
      application of 10 microM 6,7-dinitroquinoxaline-2,3-dione (DNQX) + 50 microM 2
      amino-5-phosphonopentanoic acid (AP5). In approximately 70% of ON-OFF ganglion
      cells, bicuculline (or picrotoxin) completely blocks sIPSCs, suggesting all
      sIPSCs in these cells are mediated by GABAergic synaptic vesicles and gamma
      aminobutyric acid-A (GABAA) receptors (GABAergic sIPSCs, or GABAsIPSCs). In the
      remaining 30% of - ganglion cells, bicuculline (or picrotoxin) blocks 70-98% of
      the sIPSCs, and the remaining 2-30% are blocked by strychnine (glycinergic
      sIPSCs, or GLYsIPSCs). GABAsIPSCs occur randomly with an exponentially
      distributed interval probability density function, and they persist without
      noticeable rundown over time. The GABAsIPSC frequency is greatly reduced by
      cobalt, consistent with the idea that they are largely mediated by calcium
      dependent vesicular release. GABAsIPSCs in DNQX + AP5 are tetrodotoxin (TTX)
      insensitive, suggesting that amacrine cells that release GABA under these
      conditions do not generate spontaneous action potentials. The average GABAsIPSCs
      exhibited linear current-voltage relation with a reversal potential near the
      chloride equilibrium potential, and an average peak conductance of 319.67 +/-
      252.83 (SD) pS. For GLYsIPSCs, the average peak conductance increase is 301.68 +/
      94.34 pS. These parameters are of the same order of magnitude as those measured
      in inhibitory miniature postsynaptic currents (mIPSCs) associated with single
      synaptic vesicles in the CNS. The amplitude histograms of GABAsIPSCs did not
      exhibit multiple peaks, suggesting that the larger events are not discrete
      multiples of elementary events (or quanta). We propose that each GABAsIPSC or
      GLYsIPSC in retinal ganglion cells is mediated by a single or synchronized
      multiple of synaptic vesicles with variable neurotransmitter contents. In a
      sample of 16 ON-OFF ganglion cells, the average peak leIPSC (held at 0 mV) at the
      light onset is 509.0 +/- 233.85 pA and that at the light offset is 529.0 +/-
      339.88 pA. The approximate number of GABAsIPSCs and GLYsIPSCs required to
      generate the average light responses, calculated by the ratio of the charge (area
      under current traces) of the leIPSCs to that of the average single sIPSCs, is 118
      +/- 52 for the light onset, and 132 +/- 76 for the light offset.

PMID- 9772237
TI  - Net interaction between different forms of short-term synaptic plasticity and
      slow-IPSPs in the hippocampus and auditory cortex.
AB  - Paired-pulse plasticity is typically used to study the mechanisms underlying
      synaptic transmission and modulation. An important question relates to whether,
      under physiological conditions in which various opposing synaptic properties are
      acting in parallel, the net effect is facilitatory or depressive, that is,
      whether cells further or closer to threshold. For example, does the net sum of
      paired-pulse facilitation (PPF) of excitatory postsynaptic potentials (EPSPs),
      paired-pulse depression (PPD) of inhibitory postsynaptic potentials (IPSPs), and
      the hyperpolarizing slow IPSP result in depression or facilitation? Here we
      examine how different time-dependent properties act in parallel and examine the
      contribution of gamma-aminobutyric acid-B (GABAB) receptors that mediate two
      opposing processes, the slow IPSP and PPD of the fast IPSP. Using intracellular
      recordings from rat CA3 hippocampal neurons and L-II/III auditory cortex neurons,
      we examined the postsynaptic responses to paired-pulse stimulation (with
      intervals between 50 and 400 ms) of the Schaffer collaterals and white matter,
      respectively. Changes in the amplitude, time-to-peak (TTP), and slope of each
      EPSP were analyzed before and after application of the GABAB antagonist CGP
      55845. In both CA3 and L-II/III neurons the peak amplitude of the second EPSP was
      generally depressed (further from threshold) compared with the first at the
      longer intervals; however, these EPSPs were generally broader and exhibited a
      longer TTP that could result in facilitation by enhancing temporal summation. At
      the short intervals CA3 neurons exhibited facilitation of the peak EPSP amplitude
      in the absence and presence of CGP-55845. In contrast, on average L-II/III cells
      did not exhibit facilitation at any interval, in the absence or presence of CGP
      55845. CGP-55845 generally "erased" short-term plasticity, equalizing the peak
      amplitude and TTP of the first and second EPSPs at longer intervals in the
      hippocampus and auditory cortex. These results show that it is necessary to
      consider all time-dependent properties to determine whether facilitation or
      depression will dominate under intact pharmacological conditions. Furthermore our
      results suggest that GABAB-dependent properties may be the major contributor to
      short-term plasticity on the time scale of a few hundred milliseconds and are
      consistent with the hypothesis that the balance of different time-dependent
      processes can modulate the state of networks in a complex manner and could
      contribute to the generation of temporally sensitive neural responses.

PMID- 9772238
TI  - Primate antisaccades. I. Behavioral characteristics.
AB  - The antisaccade task requires a subject to make a saccade to an unmarked location
      opposite to a flashed stimulus. This task was originally designed to study
      saccades made to a goal specified by instructions. Interest for this paradigm
      surged after the discovery that frontal lobe lesions specifically and severely
      affect human performance of antisaccades while prosaccades (i.e., saccades
      directed to the visual stimulus) are facilitated. Training monkeys to perform
      antisaccades was rarely attempted in the past, and this study is the first one
      that describes in detail the properties of such antisaccades compared with
      randomly intermingled prosaccades of varying amplitude in all directions. Such
      randomization was found essential to force the monkeys to use the instruction cue
      (pro- or anti-) and the location cue (peripheral stimulus) provided within a
      trial rather than to direct their saccades to the location of past rewards. Each
      trial began with the onset of a central fixation target that conveyed by its
      shape the instruction to make a pro- or an antisaccade to a subsequent peripheral
      stimulus. In one version of the task, the monkey was allowed to make an immediate
      saccade to the goal; in a second version, the saccade had to wait for a go
      signal. Analyses of the accuracy, velocity, and latency of antisaccades compared
      with prosaccades were performed on a sample of 7,430 pro-/antisaccades in the
      "immediate saccade" task (delayed saccades suffering from known distortions).
      Error rates fluctuated approximately 25%. Results were the same for the two
      monkeys with respect to accuracy and velocity, but they differed in terms of
      reaction time. Both monkeys generated antisaccades to stimuli in all directions,
      at various eccentricities, but antisaccades were significantly less accurate and
      slower than prosaccades elicited by the same stimuli. Interestingly, saccades to
      the stimulus could be followed by appropriate antisaccades with no intersaccadic
      interval. Such instances are here referred to as "turnaround saccades." Because
      they occurred sometimes with a long latency, turnaround saccades did not simply
      reflect the cancellation of an early foveation reflex. Consistent with human
      data, latencies of one monkey were longer for antisaccades than for prosaccades,
      but the reverse was true for the other monkey who was trained differently. In
      summary, this study demonstrates the feasibility of providing a subhuman primate
      model of antisaccade performance, but at the same time it suggests some
      irreducible differences between human and monkey performance.

PMID- 9772239
TI  - Intermittency in preplanned elbow movements persists in the absence of visual
      feedback.
AB  - It has been observed for nearly 100 years that visually guided human movements
      appear to be composed of submovements, intermittently executed overlapping
      segments. This paper presents experiments to investigate the pervasiveness of
      movement intermittency and, in particular, whether it is exclusively due to
      visual feedback. With and without visual feedback, human subjects were asked to
      1) move with constant velocity and 2) draw elliptical figures on a phase-plane
      display (showing velocity vs. position) that required cyclic movements at
      different frequencies. In both tasks, we found that removal of visual feedback
      did not significantly change movement intermittency. Subjects were unable to
      generate movements at constant speed. In addition, subjects moved less smoothly
      when drawing slower phase-plane ellipses. Furthermore, elliptical phase-plane
      figures were not always drawn at the frequency suggested by the center of the
      display. Instead, subjects moved more slowly than the tall (fast) ellipse
      displays suggested, and faster than the wide (slow) displays suggested. These
      results show that 1) movement intermittency is not exclusively due to visual
      feedback and 2) may in fact be a fundamental feature of movement behavior.

PMID- 9772240
TI  - Cell-based model of the Limulus lateral eye.
AB  - We present a cell-based model of the Limulus lateral eye that computes the eye's
      input to the brain in response to any specified scene. Based on the results of
      extensive physiological studies, the model simulates the optical sampling of
      visual space by the array of retinal receptors (ommatidia), the transduction of
      light into receptor potentials, the integration of excitatory and inhibitory
      signals into generator potentials, and the conversion of generator potentials
      into trains of optic nerve impulses. By simulating these processes at the
      cellular level, model ommatidia can reproduce response variability resulting from
      noise inherent in the stimulus and the eye itself, and they can adapt to changes
      in light intensity over a wide operating range. Programmed with these realistic
      properties, the model eye computes the simultaneous activity of its ensemble of
      optic nerve fibers, allowing us to explore the retinal code that mediates the
      visually guided behavior of the animal in its natural habitat. We assess the
      accuracy of model predictions by comparing the response recorded from a single
      optic nerve fiber to that computed by the model for the corresponding receptor.
      Correlation coefficients between recorded and computed responses were typically
      >95% under laboratory conditions. Parametric analyses of the model together with
      optic nerve recordings show that animal-to-animal variation in the optical and
      neural properties of the eye do not alter significantly its response to objects
      having the size and speed of horseshoe crabs. The eye appears robustly designed
      for encoding behaviorally important visual stimuli. Simulations with the cell
      based model provide insights about the design of the Limulus eye and its encoding
      of the animal's visual world.

PMID- 9772241
TI  - MST neurons respond to optic flow and translational movement.
AB  - We recorded the responses of 189 medial superior temporal area (MST) neurons by
      using optic flow, real translational movement, and combined stimuli in which
      matching directions of optic flow and real translational movement were presented
      together. One-half of the neurons (48%) showed strong responses to optic flow
      simulating self-movement in the horizontal plane, and 24% showed strong responses
      to translational movement. Combining optic flow stimuli with matching directions
      of translational movement caused substantial changes in both the amplitude of the
      best responses (44% of neurons) and the strength of direction selectivity (71% of
      neurons), with little effect on which stimulus direction was preferred. However,
      combining optic flow and translational movement such that opposite directions
      were presented together changed the preferred direction in 45% of the neurons
      with substantial changes in the strength of direction selectivity. These studies
      suggest that MST neurons combine visual and vestibular signals to enhance self
      movement detection and disambiguate optic flow that results from either self
      movement or the movement of large objects near the observer.

PMID- 9772242
TI  - Multiple cell types distinguished by physiological, pharmacological, and anatomic
      properties in nucleus HVc of the adult zebra finch.
AB  - Nucleus HVc of the songbird is a distinct forebrain region that is essential for
      song production and shows selective responses to complex auditory stimuli. Two
      neuronal populations within HVc give rise to its efferent projections. One
      projection, to the robust nucleus of the archistriatum (RA), serves as the
      primary motor pathway for song production, and can also carry auditory
      information to RA. The other projection of HVc begins a pathway through the
      anterior forebrain, (area X --> medial portion of the dorsolateral nucleus of the
      thalamus (DLM) --> lateral portion of the magnocellular nucleus of the anterior
      neostriatum (L-MAN) --> RA) that is crucial for song learning but, although
      active during singing, is not essential for adult song production. To test
      whether these different projection neuron classes have different functional
      properties, we recorded intracellularly from neurons in nucleus HVc in brain
      slices. We observed at least three classes of neuron based on intrinsic
      physiological and pharmacological properties as well as on synaptic inputs. We
      also examined the morphological properties of the cells by filling recorded
      neurons with neurobiotin. The different physiological cell types correspond to
      separate populations based on their soma size, dendritic extent, and axonal
      projection. Thus HVc neurons projecting to area X have large somata, show little
      spike-frequency adaptation, a hyperpolarizing response to the metabotropic
      glutamate receptor (mGluR) agonist (1S,3R)-trans-1-aminocyclopentane-1,3
      dicarboxylic acid (ACPD), and exhibit a slow inhibitory postsynaptic potential
      (IPSP) following tetanic stimulation. Those HVc neurons projecting to motor
      nucleus RA have smaller somata, show strong accommodation, are not consistently
      hyperpolarized by ACPD, and exhibit no slow IPSP. A third, rarely recorded class
      of neurons fire in a sustained fashion at very high-frequency and may be
      interneurons. Thus the neuronal classes within HVc have different functional
      properties, which may be important for carrying specific information to their
      postsynaptic targets.

PMID- 9772243
TI  - Reticulospinal systems mediate atonia with short and long latencies.
AB  - The pontomedullary region is responsible for both the tonic and phasic reduction
      of muscle activity in rapid-eye-movement sleep and contributes to the control of
      muscle tone in waking. This study focused on determining the time course of
      activity in the pontomedullary systems mediating atonia. Short-train stimulations
      (3 0.2-ms pulses at 330 Hz) of the pons and medulla suppressed neck and hindlimb
      muscle activity in decerebrate cats. We identified two distinct phases of
      suppression, early and late. The anatomic sites that produced each suppression
      were intermixed. We estimated the dividing value of the conduction velocity for
      reticulospinal projections responsible for early and late phases of hindlimb
      muscle tone suppression to be 22.8 m/s. In the medial medulla, 238 reticulospinal
      units, which send axons to the L1 level of the spinal cord, were identified.
      Pontine stimulation that suppressed hindlimb muscle tone increased the firing
      rate of 138 units (type I). Sixteen type I units showed a delayed response to the
      pontine stimulation with a latency of 10 ms or longer (type Id), whereas 122 type
      I units exhibited an earlier response (type Ie). Seven type Ie units had an
      axonal conduction velocity of <22.8 m/s, whereas the remaining 115 conducted at
      faster than 22.8 m/s. Early and late hindlimb muscle tone suppressions were
      hypothesized to be mediated through fast and slow conducting type Ie
      reticulospinal units. The activity of type Id neurons may contribute to the
      cessation of the early-phase suppression as well as to the induction,
      maintenance, or cessation of the late-phase suppression.

PMID- 9772244
TI  - Sour transduction involves activation of NPPB-sensitive conductance in mouse
      taste cells.
AB  - We examined the sour taste transduction mechanism in the mouse by applying whole
      cell patch-clamp technique to nondissociated taste cells from the fungiform
      papillae. Localized stimulation with 0.5 M NaCl and 25 mM citric acid (pH 3.0) of
      the apical membrane enabled us to obtain responses from single taste cells under
      a quasi-natural condition. Of 28 taste cells examined, 11 cells (39%) responded
      to 0. 5 M NaCl alone and 2 cells (7%) responded to 25 mM citric acid alone,
      indicating the presence of salty- and sour-specific taste cells. Ten cells (36%)
      responded to both NaCl and citric acid and 5 cells (18%) responded to neither
      salt nor citric acid. Amiloride reversibly suppressed NaCl-induced responses in
      mouse taste cells but not citric acid-induced responses. On the other hand, a Cl-
      channel blocker, 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), reversibly
      suppressed all the citric-acid-induced responses. Most of the NaCl-induced
      current responses displayed an inwardly rectifying property, whereas all the
      citric-acid-induced responses displayed an outwardly rectifying property. The
      reversal potential for NPPB-sensitive component in citric-acid-induced current
      responses was -2 +/- 7 mV (mean +/- SE, n = 4), which was close to the
      equilibrium potential of Cl- (ECl), whereas the reversal potential for NPPB
      insensitive component was 34 +/- 8 mV (n = 4). The reversal potential of citric
      acid-induced current responses (19 +/- 8 mV, n = 4) was mostly present at the
      middle point between reversal potentials of NPPB-sensitive and -insensitive
      current components. In some taste cells, an inorganic cation channel blocker,
      Cd2+, suppressed citric-acid-induced responses, but an inorganic stretch
      activated cation channel blocker, Gd3+, did not affect these responses. These
      results suggest that salt- and acid-induced responses were mediated by
      differential transduction mechanisms in mouse taste cells and that NPPB-sensitive
      Cl- channels play a more important role to sour taste transduction rather than
      amiloride-sensitive Na+ channels. However, the fact that the reversal potentials
      of citric-acid-induced responses had more positive than ECl suggests that Ca2+ or
      H+ permeable and poorly selective cation channels, which should be amiloride
      insensitive, may be activated by citric acid.

PMID- 9772245
TI  - Muscle activation patterns during two types of voluntary single-joint movement.
AB  - We examined the systematic variations in the EMG patterns during two types of
      single joint elbow movements. These patterns may be interpreted as exhibiting
      rules by which the CNS controls movement parameters. Normal human subjects
      performed two series of fast elbow flexion movements of 20-100 degrees in a
      horizontal plane manipulandum. The first series consisted of pointing movements
      (PMs) from an initial position to a target; the second series consisted of
      reversal movements (RMs) to the same targets with an immediate return to the
      starting position. Both series showed kinematic and electromyographic (EMG)
      patterns that followed our previously described speed-insensitive strategy for
      controlling movement distance. Kinematic patterns of PMs and RMs were identical
      to about the time of peak PM deceleration. Agonist EMG bursts were also initially
      the same, but RM bursts ended abruptly in a silent period, whereas PM bursts
      declined more gradually. Antagonist EMG bursts of RMs were later than those of
      PMs but were not larger, contrary to our prior expectation and despite the larger
      net extension torque during RMs. The increase in net RM extension-directed torque
      that takes the limb back to its initial position appears to be a consequence of
      reduced flexor muscle torque rather than increased extensor muscle torque. We
      propose that rules for movement control may be similar for different kinds of
      movements as long as they are functionally sufficient for the task. However, even
      in a single-joint movement paradigm, physics alone, that is, the knowledge of net
      muscle torque and limb kinematics, is not adequate to fully predict those rules
      or the muscle activation patterns they produce. These must be discovered by
      experiment. The simplest expression of such rules may not be in terms of torque
      or kinematic variables but rather explicitly in terms of muscle activation
      patterns.

PMID- 9772246
TI  - Motor patterns for human gait: backward versus forward locomotion.
AB  - Seven healthy subjects walked forward (FW) and backward (BW) at different freely
      chosen speeds, while their motion, ground reaction forces, and electromyographic
      (EMG) activity from lower limb muscles were recorded. We considered the time
      course of the elevation angles of the thigh, shank, and foot segments in the
      sagittal plane, the anatomic angles of the hip, knee, and ankle joints, the
      vertical and longitudinal ground reaction forces, and the rectified EMGs. The
      elevation angles were the most reproducible variables across trials in each
      walking direction. After normalizing the time course of each variable over the
      gait cycle duration, the waveforms of all elevation angles in BW gait were
      essentially time reversed relative to the corresponding waveforms in FW gait.
      Moreover, the changes of the thigh, shank, and foot elevation covaried along a
      plane during the whole gait cycle in both FW and BW directions. Cross-correlation
      analysis revealed that the phase coupling among these elevation angles is
      maintained with a simple reversal of the delay on the reversal of walking
      direction. The extent of FW-BW correspondence also was good for the hip angle,
      but it was smaller for the knee and ankle angles and for the ground reaction
      forces. The EMG patterns were drastically different in the two movement
      directions as was the organization of the muscular synergies measured by cross
      correlation analysis. Moreover, at any given speed, the mean EMG activity over
      the gait cycle was generally higher in BW than in FW gait, suggesting a greater
      level of energy expenditure in the former task. We argue that conservation of
      kinematic templates across gait reversal at the expense of a complete
      reorganization of muscle synergies does not arise from biomechanical constraints
      but may reflect a behavioral goal achieved by the central networks involved in
      the control of locomotion.

PMID- 9772247
TI  - ON and OFF channels of the frog optic tectum revealed by current source density
      analysis.
AB  - The spatiotemporal patterns of excitatory synaptic activity in response to
      diffuse lightON and OFF stimuli were examined by means of current source density
      (CSD) analysis. The qualitative and quantitative analyses obtained from 24 depth
      profiles for each stimulus revealed obviously different distributions of synaptic
      activity in the laminar structure. Two or three dominant current sinks I, II, and
      III were evoked in response to diffuse light ON stimulation. Sink I was observed
      at the bottom of the retinorecipient layer. Both sinks II and III, showing an
      identical spatial pattern, were observed just above sink I. On the other hand,
      diffuse light OFF stimulation elicited up to six current sinks IV, V, VI, VII,
      VIII, and IX. Sink IV was observed at the bottom of the retinorecipient layer.
      Sink V was observed in the most superficial layer. Both sinks VI and VIII were
      located between the two preceding sinks. Finally, sinks VII and IX occurred below
      the retinorecipient layer. Five electrically evoked current sinks A, B, C, D, and
      E, characterized in our previous study, were also recognized in the present
      quantitative analysis. A statistical analysis revealed that, in visually evoked
      responses, statistical differences in the spatial distribution were not present
      between sinks I and IV, and sinks II and VIII (P < 0.05). The analysis also
      showed that, in electrically evoked responses, only a pair of sinks C and E
      exhibit virtually identical spatial distribution (P < 0.05). Based on well-known
      properties of the retinal ganglion cells, possible neuronal mechanisms underlying
      each of current sinks in the ON and OFF channels and their functional meanings
      were considered. Sink I reflects the excitatory monosynaptic activity derived
      from R3 retinal ganglion cells. Sink IV reflects the excitatory monosynaptic
      activity derived from both R3 and R4 cells. Sinks V, VI, VII, and IX may be
      composed of successive polysynaptic excitatory potentials derived from
      convergence of inputs from both R3 and R4 cells. We concluded that the early four
      sinks play in particular an important role in eliciting avoidance behavior. On
      the other hand, sinks II, III, and VIII reflect excitatory synaptic activities
      derived from - retinal fibers of another type having slow conduction velocity.
      These late current sinks were suggested to mediate prey catching and its
      facilitation.

PMID- 9772248
TI  - Vasopressin-induced currents in rat neonatal spinal lateral horn neurons are G
      protein mediated and involve two conductances.
AB  - Arginine vasopressin (AVP) receptors are expressed early in the developing spinal
      cord. To characterize AVP-induced conductances in lower thoracic sympathetic
      preganglionic (SPN) and other lateral horn neurons, we used patch-clamp recording
      techniques in neonatal (11-21 days) rat spinal cord slices. Most (90%) of 273
      neurons, including all 68 SPNs, responded to AVP with membrane depolarization
      and/or a V1 receptor-mediated, dose-dependent (0.01-1.0 microM) and tetrodotoxin
      (TTX)-resistant inward current. A role for G-proteins was indicated by
      persistence of this inward current after intracellular dialysis with GTP-gamma-S
      or GMP-PNP, its marked reduction with GDP-beta-S, and significant reduction, but
      not abolition, after preincubation with pertussis toxin or in the presence of N
      ethylmaleimide. Analysis of individual current-voltage (I-V) relationships in 57
      cells indicated the presence of two different membrane conductances. In 21 cells,
      net AVP-induced currents reversed around -103 mV, reflecting reduction in one or
      more barium-sensitive potassium conductances; in 12 cells, net AVP-induced
      current reversed around -40 mV and was not significantly sensitive to several
      potassium channel blockers including barium, tetraethylammonium chloride (TEA), 4
      aminopyridine (4AP), cesium, or glibenclamide, suggesting increase in a
      nonselective cationic conductance that was separate from Ih; in 24 cells where I
      V lines shifted in parallel, AVP-induced inward currents were significantly
      greater and probably involved both conductances. These data indicate that SPNs
      and a majority of unidentified neonatal lateral horn neurons possess functional G
      protein-coupled V1-type vasopressin receptors. The wide distribution of AVP
      receptors in neonatal spinal lateral column cells suggests a role that may extend
      beyond involvement in regulation of autonomic nervous system function.

PMID- 9772249
TI  - Effects of lesions of the oculomotor vermis on eye movements in primate:
      saccades.
AB  - We studied the effects on saccades of ablation of the dorsal cerebellar vermis
      (lesions centered on lobules VI and VII) in three monkeys in which the deep
      cerebellar nuclei were spared. One animal, with a symmetrical lesion, showed
      bilateral hypometric horizontal saccades. Two animals, with asymmetrical lesions,
      showed hypometric ipsilateral saccades, and saccades to vertically positioned
      targets were misdirected, usually deviating away from the side to which
      horizontal saccades were hypometric. Postlesion, all animals showed an increase
      (2- to 5-fold) in trial-to-trial variability of saccade amplitude. They also
      showed a change in the ratio of the amplitudes of centripetal to centrifugal
      saccades (orbital-position effect); usually centrifugal saccades became smaller.
      In the two animals with asymmetrical lesions, for saccades in the hypometric
      direction, latencies were markedly increased (up to approximately 500 ms). There
      was also an absence of express and anticipatory saccades in the hypometric
      direction. When overall saccade latency was increased, centrifugal saccades
      became relatively more delayed than centripetal saccades. The dynamic
      characteristics of saccades were affected to some extent in all monkeys with
      changes in peak velocity, eye acceleration, and especially eye deceleration.
      There was relatively little effect of orbital position on saccade dynamics,
      however, with the exception of one animal that showed an orbital position effect
      for eye acceleration. In a double-step adaptation paradigm, animals showed an
      impaired ability to adaptively adjust saccade amplitude, though increased
      amplitude variability postlesion may have played a role in this deficit. During a
      single training session, however, the latency to corrective saccades-which had
      been increased postlesion-gradually decreased and so enabled the animal to reach
      the final position of the target more quickly. Overall, both in the early
      postlesion period and during recovery, changes in saccade amplitude and latency
      tended to vary together but not with changes in saccade dynamics or adaptive
      capability, both of which behaved relatively independently. These findings
      suggest that the cerebellum can adjust saccade amplitude and saccade dynamics
      independently. Our results implicate the cerebellar vermis directly in every
      aspect of the on-line control of saccades: initiation (latency), accuracy
      (amplitude and direction), and dynamics (velocity and acceleration) and also in
      the acquisition of adaptive ocular motor behavior.

PMID- 9772250
TI  - Coexpression of multiple metabotropic glutamate receptors in axon terminals of
      single suprachiasmatic nucleus neurons.
AB  - Glutamate is the primary excitatory transmitter in axons innervating the
      hypothalamic suprachiasmatic nucleus (SCN) and is responsible for light-induced
      phase shifts of circadian rhythms generated by the SCN. By using self-innervating
      single neuron cultures and patch-clamp electrophysiology, we studied metabotropic
      glutamate receptors (mGluRs) expressed by SCN neurons. The selective agonists for
      group I (3,5-dihydroxy-phenylglycine), group II ((S)-4-carboxy-3
      hydroxyphenylglycine), and group III ((+)-2-amino-4-phosphonobutyric acid) mGluRs
      all depressed the evoked IPSC in a subset (33%) of single autaptic neurons,
      suggesting a coexpression of all three groups of mGluRs in the same axon
      terminals of a single neuron. Other neurons showed a variety of combinations of
      mGluRs, including an expression of only one group of mGluR (18%) or coexpression
      of two groups of mGluRs (27%). Some neurons had no response to any of the three
      agonists (22%). The three mGluR agonists had no effect on postsynaptic gamma
      aminobutyric acid (GABA) receptor responses, indicating a presynaptic modulation
      of GABA release by mGluRs. We conclude that multiple mGluRs that act through
      different second messenger pathways are coexpressed in single axon terminals of
      SCN neurons where they modulate the release of GABA presynaptically, usually
      inhibiting release.

PMID- 9772251
TI  - EMG responses to maintain stance during multidirectional surface translations.
AB  - To characterize muscle synergy organization underlying multidirectional control
      of stance posture, electromyographic activity was recorded from 11 lower limb and
      trunk muscles of 7 healthy subjects while they were subjected to horizontal
      surface translations in 12 different, randomly presented directions. The latency
      and amplitude of muscle responses were quantified for each perturbation
      direction. Tuning curves for each muscle were examined to relate the amplitude of
      the muscle response to the direction of surface translation. The latencies of
      responses for the shank and thigh muscles were constant, regardless of
      perturbation direction. In contrast, the latencies for another thigh [tensor
      fascia latae (TFL)] and two trunk muscles [rectus abdominis (RAB) and erector
      spinae (ESP)] were either early or late, depending on the perturbation direction.
      These three muscles with direction-specific latencies may play different roles in
      postural control as prime movers or as stabilizers for different translation
      directions, depending on the timing of recruitment. Most muscle tuning curves
      were within one quadrant, having one direction of maximal activity, generally in
      response to diagonal surface translations. Two trunk muscles (RAB and ESP) and
      two lower limb muscles (semimembranosus and peroneus longus) had bipolar tuning
      curves, with two different directions of maximal activity, suggesting that these
      muscle can play different roles as part of different synergies, depending on
      translation direction. Muscle tuning curves tended to group into one of three
      regions in response to 12 different directions of perturbations. Two muscles
      [rectus femoris (RFM) and TFL] were maximally active in response to lateral
      surface translations. The remaining muscles clustered into one of two diagonal
      regions. The diagonal regions corresponded to the two primary directions of
      active horizontal force vector responses. Two muscles (RFM and adductor longus)
      were maximally active orthogonal to their predicted direction of maximal activity
      based on anatomic orientation. Some of the muscles in each of the synergic
      regions were not anatomic synergists, suggesting a complex central organization
      for recruitment of muscles. The results suggest that neither a simple reflex
      mechanism nor a fixed muscle synergy organization is adequate to explain the
      muscle activation patterns observed in this postural control task. Our results
      are consistent with a centrally mediated pattern of muscle latencies combined
      with peripheral influence on muscle magnitude. We suggest that a flexible
      continuum of muscle synergies that are modifiable in a task-dependent manner be
      used for equilibrium control in stance.

PMID- 9772252
TI  - Voltage-dependent uptake is a major determinant of glutamate concentration at the
      cone synapse: an analytical study.
AB  - It was suggested that glutamate concentration at the synaptic terminal of the
      cones was controlled primarily by a voltage-dependent glutamate transporter and
      that diffusion played a less important role. The conclusion was based on the
      observation that the rate of glutamate concentration during the hyperpolarizing
      light response was dramatically slowed when the transporter was blocked with
      dihydrokainate although diffusion remained intact. To test the validity of this
      notion we constructed a model in which the balance among uptake, diffusion, and
      release determined the flow of glutamate into and out of the synaptic cleft. The
      control of glutamate concentration was assumed here to be determined by two
      relationships; 1) glutamate concentration is the integral over the synaptic
      volume of the rates of release, uptake, and diffusion, and 2) membrane potential
      is the integral over the membrane capacitance of the dark, leak, and transporter
      gated chloride current. These relationships are interdependent because glutamate
      uptake via the transporter is voltage dependent and because the transporter-gated
      current is concentration dependent. The voltage and concentration dependence of
      release and uptake, as well as the light-elicited, transporter-gated, and leak
      currents were measured in other studies. All of these measurements were
      incorporated into our predictive model of glutamate uptake. Our results show a
      good quantitative fit between the predicted and the measured magnitudes and rates
      of change of glutamate concentration, derived from the two interdependent
      relationships. This close fit supports the validity of these two relationships as
      descriptors of the mechanisms underlying the control of glutamate concentration,
      it verifies the accuracy of the experimental data from which the functions used
      in these relationships were derived, and it lends further support to the notion
      that glutamate concentration is controlled primarily by uptake at the
      transporter.

PMID- 9772253
TI  - Corticomotoneuronal postspike effects in shoulder, elbow, wrist, digit, and
      intrinsic hand muscles during a reach and prehension task.
AB  - We used spike-triggered averaging of rectified electromyographic activity to
      determine whether corticomotoneuronal (CM) cells produce postspike effects in
      muscles of both proximal and distal forelimb joints in monkeys performing a reach
      and prehension task. Two monkeys were trained to perform a self-paced task in
      which they reached forward from a starting position to retrieve a food reward
      from a small cylindrical well. We compiled spike-triggered averages from 22 to 24
      separate forelimb muscles at both proximal (shoulder, elbow) and distal (wrist,
      digits, intrinsic hand) joints. Of 174 cells examined, 112 produced postspike
      effects in at least one of the target muscles. Of those cells, 45.5% produced
      postspike effects in both proximal and distal forelimb muscles. A nearly equal
      number (44.7%) produced postspike effects in distal muscles only, whereas a clear
      minority (9.8%) produced postspike effects in only proximal muscles. The majority
      of CM cells (71.4%) produced effects in two or more muscles, with an average
      muscle field of 3.1 +/- 2.1 (mean +/- SD) for facilitation plus suppression. Of
      345 postspike effects identified, 70.7% were facilitation effects and 29.3% were
      suppression effects. The large majority of effects (72.2%) were in distal
      muscles. When averaged by joint, the latency and peak magnitude of postspike
      facilitation showed a stepwise increase from proximal to distal joints. The
      results of this study show that the majority of CM cells engaged in coordinated
      forelimb reaching movements facilitate and/or suppress muscles at multiple
      joints, including muscles at both proximal and distal joints. The results also
      show that CM cells make more frequent and more potent terminations in motoneuron
      pools of distal compared with proximal muscles.

PMID- 9772254
TI  - Group I metabotropic glutamate receptors mediate slow inhibition of calcium
      current in neocortical neurons.
AB  - Metabotropic glutamate receptor (mGluR)-mediated inhibition of high-voltage
      activated Ca2+ currents was investigated in pyramidal neurons acutely isolated
      from rat dorsal frontoparietal neocortex. Whole cell recordings were made at 30
      32 degrees C, with Ca2+ as the charge carrier. Selective agonists were used to
      classify the subgroup of mGluRs mediating the response. Ca2+ currents were
      inhibited by (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S, 3R-ACPD) and
      by the group I agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) but not by the
      group II agonist (2S,2'R,3'R)-2-(2', 3'-dicarboxycyclopropyl)glycine (DCG-IV) or
      the group III agonist (+)-2-amino-4-phosphonobutryic acid (-AP4). (2S,1'S, 2'S)-2
      (carboxycyclopropyl)glycine (-CCG-I) was effective at 10 and 100 microM but not
      at 1 microM, consistent with involvement of group I mGluRs. Variable results were
      obtained with the putative mGluR5-selective agonist (RS)-2-chloro-5
      hydroxyphenylglycine (CHPG) and the putative mGluR1-selective antagonist (S)-4
      carboxyphenylglycine [(S)-4CPG], indicating that the group I mGluR subtypes may
      vary between cells or that these compounds were activating other receptors. The
      actions of (+)-alpha-methyl-4-carboxyphenylglycine [(+)-MCPG] were consistent
      with it being a low-potency antagonist. Several features of the Ca2+ current
      inhibition evoked by DHPG distinguished it from the rapid modulation typical of a
      direct action of G proteins on Ca2+ channels; the inhibition was slow to reach
      maximum (tens of seconds), current activation was not slowed or shifted in the
      positive voltage direction, and the inhibition was not relieved by positive
      prepulses. Nimodipine and omega-conotoxin GVIA blocked fractions of the current
      and also reduced the magnitude of the responses to DHPG, indicating that both L-
      and N-type Ca2+ channels were regulated. These results further differentiate the
      slow modulatory pathway observed in neocortical neurons when Ca2+ is used as the
      charge carrier from the rapid voltage-dependent mechanism reported to inhibit
      Ba2+ currents under Ca2+-free conditions.

PMID- 9772255
TI  - Mechanisms for force adjustments to unpredictable frictional changes at
      individual digits during two-fingered manipulation.
AB  - Previous studies on adaptation of fingertip forces to local friction at
      individual digit-object interfaces largely focused on static phases of
      manipulative tasks in which humans could rely on anticipatory control based on
      the friction in previous trials. Here we instead analyze mechanisms underlying
      this adaptation after unpredictable changes in local friction between consecutive
      trials. With the tips of the right index and middle fingers or the right and left
      index fingers, subjects restrained a manipulandum whose horizontal contact
      surfaces were located side by side. At unpredictable moments a tangential force
      was applied to the contact surfaces in the distal direction at 16 N/s to a
      plateau at 4 N. The subjects were free to use any combination of normal and
      tangential forces at the two fingers, but the sum of the tangential forces had to
      counterbalance the imposed load. The contact surface of the right index finger
      was fine-grained sandpaper, whereas that of the cooperating finger was changed
      between sandpaper and the more slippery rayon. The load increase automatically
      triggered normal force responses at both fingers. When a finger contacted rayon,
      subjects allowed slips to occur at this finger during the load force increase
      instead of elevating the normal force. These slips accounted for a partitioning
      of the load force between the digits that resulted in an adequate adjustment of
      the normal:tangential force ratios to the local friction at each digit. This
      mechanism required a fine control of the normal forces. Although the normal force
      at the more slippery surface had to be comparatively low to allow slippage, the
      normal forces applied by the nonslipping digit at the same time had to be high
      enough to prevent loss of the manipulandum. The frictional changes influenced the
      normal forces applied before the load ramp as well as the size of the triggered
      normal force responses similarly at both fingers, that is, with rayon at one
      contact surface the normal forces increased at both fingers. Thus to
      independently adapt fingertip forces to the local friction the normal forces were
      controlled at an interdigital level by using sensory information from both
      engaged digits. Furthermore, subjects used both short- and long-term anticipatory
      mechanisms in a manner consistent with the notion that the central nervous system
      (CNS) entertains internal models of relevant object and task properties during
      manipulation.

PMID- 9772256
TI  - Pre- and postsynaptic inhibitory actions of methionine-enkephalin on identified
      bulbospinal neurons of the rat RVL.
AB  - The effects of methionine-enkephalin (ME) on visualized bulbospinal neurons of
      the rostral ventrolateral medulla (RVL) were characterized in thin slices at 32
      degrees C using the whole cell patch-clamp technique. Thirty-five percent of the
      recorded neurons were found to be tyrosine hydroxylase immunoreactive (C1
      neurons). In voltage-clamp recordings, ME (3 microM) induced an outward current
      in 66% of RVL bulbospinal neurons. A similar percentage of C1 and non-C1 neurons
      were opioid sensitive. The current induced by ME was inwardly rectifying,
      reversed close to the potassium equilibrium potential, and was blocked by barium.
      Most spontaneous postsynaptic currents recorded in these neurons were
      tetrodotoxin (TTX)-resistant miniature postsynaptic currents (mPSCs).
      Approximately, 75% of mPSCs had rapid kinetics (decay time = 4.7 ms) and were
      glutamatergic [miniature excitatory postsynaptic currents (mEPSCs)] because they
      were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM). The remaining
      mPSCs had much slower kinetics (decay time = 19.6 ms) and were GABAergic
      [miniature inhibitory postsynaptic currents (mIPSCs)] as they were blocked by
      gabazine (3 microM) but not by strychnine (3-10 microM). ME decreased the
      frequency of mEPSCs and mIPSCs by 69 and 43%, respectively. The inhibitory
      effects of ME were mimicked by the selective mu-opioid receptor agonist
      endomorphin-1 (EM, 3 microM) and were blocked by naloxone (1 microM). In the
      absence of TTX, excitatory PSCs evoked by focal electrical stimulation were
      isolated by application of gabazine and strychnine. EM reduced the amplitude of
      the evoked EPSCs by 41% without changing their decay time. We conclude that
      opioids inhibit the majority of RVL C1 and non-C1 bulbospinal neurons by
      activating a potassium conductance postsynaptically and by decreasing the
      presynaptic release of glutamate. These cellular mechanisms could explain the
      depressive cardiovascular effects and the sympathoinhibition produced by opioid
      transmitters in the RVL, in particular during hypotensive hemorrhage.

PMID- 9772257
TI  - Fictive gill and lung ventilation in the pre- and postmetamorphic tadpole brain
      stem.
AB  - The pattern of efferent neural activity recorded from the isolated brain stem
      preparation of the tadpole Rana catesbeiana was examined to characterize fictive
      gill and lung ventilations during ontogeny. In vitro recordings from cranial
      nerve (CN) roots V, VII, and X and spinal nerve (SN) root II of premetamorphic
      tadpoles showed a coordinated sequence of rhythmic bursts occurring in one of two
      patterns, pattern1, high-frequency, low-amplitude bursts lacking corresponding
      activity in SN II and pattern 2, low-frequency, high-amplitude bursts with
      coincident bursts in SN II. These two patterns corresponded to gill and lung
      ventilatory burst patterns, respectively, recorded from nerve roots of
      decerebrate, spontaneously breathing tadpoles. Similar patterns were observed in
      brain stem preparations from postmetamorphic tadpoles except that they showed a
      greater frequency of lung bursts and they expressed fictive gill ventilation in
      SN II. The laryngeal branch of the vagus (Xl) displayed efferent bursts in phase
      with gill and lung activity, suggesting fictive glottal constriction during gill
      ventilation and glottal dilation during lung ventilation. The fictive gill
      ventilatory cycle of pre- and postmetamorphic tadpoles was characterized by a
      rostral to caudal sequence of CN bursts. The fictive lung ventilatory pattern in
      the premetamorphic animal was initiated by augmenting CN VII discharge followed
      by synchronous bursts in CN V, X, SN II, and Xl. By contrast, postmetamorphic
      patterns of fictive lung ventilation were characterized by lung burst activity in
      SN II that preceded burst onset in CN V and followed the lead burst in CN VII. We
      conclude that recruitment and timing of pattern 1 and pattern 2 rhythmic bursts
      recorded in vitro closely resemble that recorded during spontaneous respiratory
      behavior, indicating that the two patterns are the neural equivalent of gill and
      lung ventilation, respectively. Further, fictive gill and lung ventilatory
      patterns in postmetamorphic tadpoles differ in burst onset latency from
      premetamorphic tadpole patterns and resemble fictive oropharyngeal and pulmonary
      burst cycles in adult frogs.

PMID- 9772258
TI  - Synaptic activation of plateaus in hindlimb motoneurons of decerebrate cats.
AB  - Intracellular recordings were made from hindlimb motoneurons in decerebrate cats
      to study how synaptic inputs could affect the threshold at which plateau
      potentials are activated with current injections through the recording
      microelectrode in the cell body. This study was prompted by recent evidence that
      the noninactivating inward currents that regeneratively produce the plateau
      potentials arise (partly) from dendritic conductances, which may be relatively
      more accessible to synaptic input than to current injected into the soma.
      Initially, cells were studied by injecting a slow triangular current ramp
      intracellularly to determine the threshold for activation of the plateau. In
      cells where the sodium spikes were blocked with intracellular QX314, plateau
      activation was readily seen as a sudden jump in membrane potential, which was not
      directly reversed as the current was decreased. With normal spiking, the plateau
      activation (the noninactivating inward current) was reflected by a steep and
      sustained jump in firing rate that was not directly reversed as the current was
      decreased. Importantly, the threshold for plateau activation (at 34 Hz on
      average) was significantly above the recruitment level (13 Hz on average). When
      tonic synaptic excitation [excitatory postsynaptic potentials (EPSPs)] was
      provided either by stretching the triceps surae muscle or by stimulating its
      nerve at a high frequency, the threshold for plateau activation by intracellular
      current injection was significantly lowered (by 12 Hz or 5.8 mV on average,
      without and with QX314, respectively). Conversely, tonic synaptic inhibition
      [inhibitory postsynaptic potentials (IPSPs)], provided by appropriate nerve
      stimulation, significantly raised the plateau threshold (by 19 Hz or 7.6 mV on
      average). These effects were graded with the intensity of tonic EPSPs and IPSPs.
      Strong enough EPSPs brought the plateau threshold down sufficiently that it was
      activated by the intracellular current soon after recruitment. A further increase
      in tonic EPSPs recruited the cell directly, and in this case the plateau was
      activated at or before recruitment. The finding that synaptic excitation can
      produce plateau activation below the recruitment level is of importance for the
      interpretation of its function. With this low-threshold activation, the plateau
      potentials are likely important in securing an effective recruitment to
      frequencies that produce significant force generation and would subsequently have
      no further affect on the frequency modulation, other than to provide a steady
      depolarizing bias that would help to sustain firing (cf. self-sustained firing).
      Additional jumps in frequency after recruitment (i.e., bistable firing) would not
      be expected.

PMID- 9772259
TI  - Short-term plasticity in hindlimb motoneurons of decerebrate cats.
AB  - Cat hindlimb motoneurons possess noninactivating voltage-gated inward currents
      that can, under appropriate conditions, regeneratively produce sustained
      increments in depolarization and firing of the cell (i.e., plateau potentials).
      Recent studies in turtle dorsal horn neurons and motoneurons indicate that
      facilitation of plateaus occurs with repeated plateau activation (decreased
      threshold and increased duration; this phenomenon is referred to as warm-up). The
      purpose of the present study was to study warm-up in cat motoneurons. Initially,
      cells were studied by injecting a slow triangular current ramp intracellularly to
      determine the threshold for activation of the plateau. In cells where the sodium
      spikes were blocked with intracellular QX314, plateau activation was readily seen
      as a sudden jump in membrane potential, which was not directly reversed as the
      current was decreased (cf. hysteresis). With normal spiking, the plateau
      activation (the noninactivating inward current) was reflected by a steep and
      sustained jump in firing rate, which was not directly reversed as the current was
      decreased (hysteresis). Repetitive plateau activation significantly lowered the
      plateau activation threshold in 83% of cells (by on average 5 mV and 11 Hz with
      and without QX314, respectively). This interaction between successive plateaus
      (warm-up) occurred when tested with 3- to 6-s intervals; no interaction occurred
      at times >20 s. Plateaus initiated by synaptic activation from muscle stretch
      were also facilitated by repetition. Repeated slow muscle stretches that produced
      small phasic responses when a cell was hyperpolarized with intracellular current
      bias produced a larger and more prolonged responses (plateau) when the bias was
      removed, and the amplitude and duration of this response grew with repetition.
      The effects of warm-up seen with intracellular recordings during muscle stretch
      could also be recorded extracellularly with gross electromyographic (EMG)
      recordings. That is, the same repetitive stretch as above produced a
      progressively larger and more prolonged EMG response. Warm-up may be a
      functionally important form of short-term plasticity in motoneurons that secures
      efficient motor output once a threshold level is reached for a significant
      period. Finally, the finding that warm-up can be readily observed with gross EMG
      recordings will be useful in future studies of plateaus in awake animals and
      humans.

PMID- 9772260
TI  - Role of the oculomotor vermis in generating pursuit and saccades: effects of
      microstimulation.
AB  - We studied the eye movements evoked by applying small amounts of current (2-50
      microA) within the oculomotor vermis of two monkeys. We first compared the eye
      movements evoked by microstimulation applied either during maintained pursuit or
      during fixation. Smooth, pursuitlike changes in eye velocity caused by the
      microstimulation were directed toward the ipsilateral side and occurred at short
      latencies (10-20 ms). The amplitudes of these pursuitlike changes were larger
      during visually guided pursuit toward the contralateral side than during either
      fixation or visually guided pursuit toward the ipsilateral side. At these same
      sites, microstimulation also often produced abrupt, saccadelike changes in eye
      velocity. In contrast to the smooth changes in eye velocity, these saccadelike
      effects were more prevalent during fixation and during pursuit toward the
      ipsilateral side. The amplitude and type of evoked eye movements could also be
      manipulated at single sites by changing the frequency of microstimulation.
      Increasing the frequency of microstimulation produced increases in the amplitude
      of pursuitlike changes, but only up to a certain point. Beyond this point, the
      value of which depended on the site and whether the monkey was fixating or
      pursuing, further increases in stimulation frequency produced saccadelike changes
      of increasing amplitude. To quantify these effects, we introduced a novel method
      for classifying eye movements as pursuitlike or saccadelike. The results of this
      analysis showed that the eye movements evoked by microstimulation exhibit a
      distinct transition point between pursuit and saccadelike effects and that the
      amplitude of eye movement that corresponds to this transition point depends on
      the eye movement behavior of the monkey. These results are consistent with
      accumulating evidence that the oculomotor vermis and its associated deep
      cerebellar nucleus, the caudal fastigial, are involved in the control of both
      pursuit and saccadic eye movements. We suggest that the oculomotor vermis might
      accomplish this role by altering the amplitude of a motor error signal that is
      common to both saccades and pursuit.

PMID- 9772261
TI  - Segregation of receptive field properties in the lateral geniculate nucleus of a
      New-World monkey, the marmoset Callithrix jacchus.
AB  - The lateral geniculate nucleus (LGN) in humans and Old-World monkeys is dominated
      by the representation of the fovea in the parvocellular (PC) layers, and most PC
      cells in the foveal representation have red-green cone opponent receptive field
      properties. It is not known whether these features are both unique to
      trichromatic primates. Here we measured receptive field properties and the
      visuotopic organization of cells in the LGN of a New-World monkey, the marmoset
      Callithrix jacchus. The marmoset displays a polymorphism of cone opsins in the
      medium-long wavelength (ML) range, which allows the LGN of dichromatic ("red
      green color blind") and trichromatic individuals to be compared. Furthermore, the
      koniocellular-interlaminar layers are segregated from the main PC layers in
      marmoset, allowing the functional role of this subdivision of the LGN to be
      assessed. We show that the representation of the visual field in the LGN is
      quantitatively similar in dichromatic and trichromatic marmosets and is similar
      to that reported for macaque; the vast majority of LGN volume is devoted to the
      central visual field. ON- and OFF-type responses are partially segregated in the
      PC layers so that responses are more commonly encountered near the external
      border of each layer. The red-green (ML) opponent cells in trichromatic animals
      were all located in the PC layers, and their receptive fields were within 16
      degrees of the fovea. The koniocellular zone between the PC and magnocellular
      layers contained cells that receive excitatory input from short wavelength
      sensitive cones ("blue- cells") as well as other nonopponent cells. These results
      suggest that the basic organization of the LGN is common to dichromatic and
      trichromatic primates and provide further evidence that ML and SWS opponent
      signals are carried in distinct subdivisions of the retinogeniculocortical
      pathway.

PMID- 9772262
TI  - Painful stimuli evoke potentials recorded from the parasylvian cortex in humans.
AB  - Cutaneous stimulation of the face and hand with a CO2 laser in three awake
      patients evoked potentials (LEPs) recorded from the dominant left parasylvian
      cortex. These were recorded by means of a subdural grid of electrodes implanted
      for evaluation of epilepsy. Stimulation of the contralateral face resulted in
      waveforms consisting of a negative potential (N2, 162 +/- 5 ms; mean +/- SE)
      followed by a positive potential (P2, 340 +/- 18 ms). Both waves occurred at
      longer latency after hand than after facial stimulation. N2 and P2 potentials
      recorded from the grid correspond well in morphology to those recorded from the
      scalp in four additional patients tested with the same stimulation paradigm. The
      N2 waves recorded from the subdural grid occurred at significantly shorter
      latencies than did those recorded from the scalp (184 +/- 6 ms), but the P2 waves
      at the grid occurred at significantly longer latencies than did those recorded at
      the scalp (281 +/- 13 ms). The amplitudes of the potentials recorded from the
      grid were maximal over the parietal operculum both for contralateral stimulation
      of the face or hand and for ipsilateral stimulation of the face. Potentials also
      were recorded in this area after stimulation of the ipsilateral hand. The
      cortical distributions of these potentials suggest that their generators are
      located in the parietal operculum or in the insula, or in both, consistent with
      previous PET, magnetoencephalographic, and scalp LEP source analyses. These
      previous analyses provide indirect evidence of nociceptive input to parasylvian
      cortex because the interpretation of each analysis incorporates multiple
      assumptions. The present results are the first direct evidence of nociceptive
      input to the human parasylvian cortex.

PMID- 9772263
TI  - High safety factor for action potential conduction along axons but not dendrites
      of cultured hippocampal and cortical neurons.
AB  - By using a combination of Ca2+ imaging and current-clamp recording, we previously
      reported that action potential (AP) conduction is reliably observed from the soma
      to axonal terminals in cultured cortical neurons. To extend these studies, we
      evaluated Ca2+ influx evoked by Na+ APs as a marker of AP conduction under
      conditions that are expected to lower the conduction safety factor to explore
      mechanisms of axonal and dendritic excitability. As expected, reducing the
      extracellular Na+ concentration from 150 to approximately 60 mM decreased the
      amplitude of APs recorded in the soma but surprisingly did not influence axonal
      conduction, as monitored by measuring Ca2+ transients. Furthermore, reliable
      axonal conduction was observed in dilute (20 nM) tetrodotoxin (TTX), despite a
      similar reduction in AP amplitude. In contrast, the Ca2+ transient measured along
      dendrites was markedly reduced in low Na+, although still mediated by TTX
      sensitive Na+ channels. Dendritic action-potential evoked Ca2+ transients were
      also markedly reduced in 20 nM TTX. These data provide further evidence that
      strongly excitable axons are functionally compartmentalized from weakly excitable
      dendrites. We conclude that modulation of Na+ currents or membrane potential by
      neurotransmitters or repetitive firing is more likely to influence neuronal
      firing before AP generation than the propagation of signals to axonal terminals.
      In contrast, the relatively low safety factor for back-propagating APs in
      dendrites would suggest a stronger effect of Na+ current modulation.

PMID- 9772264
TI  - Gustatory responses of the hamster Mesocricetus auratus to various compounds
      considered sweet by humans.
AB  - The taste of 30 compounds was studied in the golden hamster with three different
      methods: single-fiber recordings, two-bottle preference (TBP), and conditioned
      taste aversion (CTA) tests. On the whole, the results showed that the sense of
      taste in the hamster differs in many respects from that in humans because, of 26
      tested compounds known as sweet to humans, 11 had no taste or tasted differently.
      The results also supported the notion that activity in S-fibers elicits liking
      and activity in Q- or H-fibers rejection. Specifically hierarchial cluster
      analysis of 36 single fibers from the chorda tympani proper nerve separated N-, H
      , and S-clusters consisting of 11 sucrose-, 14 NaCl-, and 11 citric-best fibers.
      Ace-K, cyanosuosan, N-4-cyanophenyl-N'-cyanoguanidineacetate (CCGA), -tryptophan,
      N-3, 5-dichlorophenyl-N'-(S)-alpha-methylbenzylguanidineacetate (DMGA),
      saccharin, SC-45647, and suosan stimulated only the S-fibers, were significantly
      preferred in TBP tests, and generalized to sucrose in the CTA tests. Ethylene
      glycol stimulated the N-fibers in addition to the S-fibers. This explains its
      generalization to sucrose in CTA. Its toxicity may contribute to its rejection in
      TBP tests. Sodium cyclamate stimulated a few N- but no S-fibers, which may
      explain the nondiscriminatory TBP and CTA results. Glycine elicited its largest
      response in the S-fibers, although it also stimulated other fibers. The resulting
      mixed taste sensation may explain why it was not preferred in TBP, although it
      generalized to sucrose in the CTA. Alitame, aspartame, N-4-cyanophenylcarbamoyl-
      aspartyl-(R)-alpha-methylbenzylamine (CAM), N-4-cyanophenylcarbamoyl-(R, S)-3
      amino-3-(3, 4-methylenedioxyphenyl) propionic acid (CAMPA), N-(S)-2
      methylhexanoyl--glutamyl-5-amino-2-pyridinecarbonitrile (MAGAP), N-1-naphthoyl-
      glutamyl-5-amino-2-pyridinecarbonitrile (NAGAP), NHDHC, superaspartame, and
      thaumatin were among the compounds considered sweet by humans that gave no
      response, were not discriminated in the TBP test, and gave no generalization in
      the CTA tests.

PMID- 9772265
TI  - Alterations in average spectrum of cochleoneural activity by long-term salicylate
      treatment in the guinea pig: a plausible index of tinnitus.
AB  - Salicylate, one of the most widely used drugs, produces at repetitive high doses
      reversible tinnitus and hearing loss. Neural correlates of hearing loss have long
      been established, whereas they remain elusive for tinnitus. The average spectrum
      of electrophysiological cochleoneural activity (ASECA), a measure of spontaneous
      auditory nerve activity, was monitored in guinea pigs over weeks of salicylate
      administration. Auditory nerve compound action potential (CAP) was also recorded
      to monitor acoustic sensitivity. In the first days of treatment, ASECA decreased
      acutely during hours after salicylate administration; after several days this
      decrease could be reduced. Over weeks of treatment the level of ASECA increased
      progressively. No change in CAP threshold was observed. The ASECA decrease
      induced by a contralateral broadband noise remained unchanged. At the end of
      treatment, acoustic tuning of ASECA showed a partially decreased sensitivity.
      After cessation of treatment the ASECA level returned progressively to initial
      values. In control animals delivery of an ipsilateral acoustic noise could
      reproduce the ASECA increase observed in long-term salicylate-treated animals.
      This white noise was of moderate sound pressure level and it elevated slightly
      CAP thresholds at high frequencies. These data provide evidence for salicylate
      induced ASECA alterations without changes in CAP thresholds, in accord with
      clinical reports of tinnitus being the first subjective sign of salicylate
      ototoxicity. The similarities in occurrence, development, reversibility,
      frequency content, and acoustic level support the idea that ASECA changes, which
      indicates alterations of spontaneous eighth nerve activity and reflects the
      presence of salicylate-induced high-pitch tinnitus.

PMID- 9772266
TI  - Action potential and sodium current in the slowly and rapidly adapting stretch
      receptor neurons of the crayfish (Astacus astacus).
AB  - Action potentials (APs) and sodium current from the slowly and the rapidly
      adapting stretch receptor neurons in the crayfish (Astacus astacus) were recorded
      with a two microelectrode voltage- and current-clamp technique. In the rapidly
      adapting neuron the APs had a duration of 3.2 +/- 0.2 ms (means +/- SE) and an
      amplitude of 55.2 +/- 1.5 mV. In the slowly adapting receptor neuron APs had a
      duration of 4.1 +/- 0.2 ms and an amplitude 79.9 +/- 2.0 mV. APs in the rapidly
      adapting neuron had a larger amplitude if they were recorded from the axon. In
      the rapidly adapting neuron adaptation of the impulse response was prolonged by
      hyperpolarization or by exposure to scorpion venom. Also, sinusoidal current
      stimulation added to the current steps prevented impulse adaptation. Block of the
      potassium currents in the slowly adapting neuron resulted in a rapid adaptation
      of the impulse response. The maximum sodium current amplitude was 313 +/- 15 nA
      in slowly adapting neuron and 267 +/- 11 nA in the rapidly adapting neuron. The
      current-voltage relationship showed a hump most marked in the slowly adapting
      neuron and abolished when a depolarizing prepulse was given. In the rapidly
      adapting neuron the inactivation starts at a more negative potential (Eh = -45
      mV) and is faster compared with the slowly adapting neuron (Eh = -41 mV). The
      crude scorpion venom of Leiurus quinquestriatus (ScVLq) shifted hinfinity curve
      toward more positive potentials and slowed down the rate of inactivation. The
      results indicate the possible presence of more than one Na+ channel population
      and that the relative density and the spatial distribution is different in the
      slowly and rapidly adapting neuron. The difference contributes to the adaptive
      properties of the two receptor neurons.

PMID- 9772267
TI  - Azimuth coding in primary auditory cortex of the cat. I. Spike synchrony versus
      spike count representations.
AB  - The neural representation of sound azimuth in auditory cortex most often is
      considered to be average firing rate, and azimuth tuning curves based thereupon
      appear to be rather broad. Coincident firings of simultaneously recorded neurons
      could provide an improved representation of sound azimuth compared with that
      contained in the firing rate in either of the units. In the present study, a
      comparison was made between local field potentials and several measures based on
      unit firing rate and coincident firing with respect to their azimuth-tuning curve
      bandwidth. Noise bursts, covering a 60-dB intensity range, were presented from
      nine speakers arranged in a semicircular array with a radius of 55 cm in the
      animal's frontal half field. At threshold intensities, all local field potential
      (LFP) recordings showed preferences for contralateral azimuths. Multiunit
      recordings showed in 74% a threshold for contralateral azimuths, in 16% for
      frontal azimuths, and in only 5% showed an ipsilateral threshold. The remaining
      5% were not spatially tuned. Representations for directionally sensitive units
      based on coincident firings provided significantly sharper tuning (50-60 degrees
      bandwidth at 25 dB above the lowest threshold) than those based on firing rate
      (bandwidths of 80-90 degrees). The ability to predict sound azimuth from the
      directional information contained in the neural population activity was simulated
      by combining the responses of the 102 single units. Peak firing rates and
      coincident firings with LFPs at the preferred azimuth for each unit were used to
      construct a population vector. At stimulus levels of >/=40 dB SPL, the prediction
      function was sigmoidal with the predicted frontal azimuth coinciding with the
      frontal speaker position. Sound azimuths >45 degrees from the midline all
      resulted in predicted values of -90 or 90 degrees, respectively. No differences
      were observed in the performance of the prediction based on firing rate or
      coincident firings for these intensities. This suggests that although coincident
      firings produce narrower azimuth tuning curves, the information contained in the
      overall neural population does not increase compared with that contained in a
      firing rate representation. The relatively poor performance of the population
      vector further suggests that primary auditory cortex does not code sound azimuth
      by a globally distributed measure of peak firing rate or coincident firing.

PMID- 9772268
TI  - Azimuth coding in primary auditory cortex of the cat. II. Relative latency and
      interspike interval representation.
AB  - This study was designed to explore a potential representation of sound azimuth in
      the primary auditory cortex (AI) of the cat by the relative latencies of a
      population of neurons. An analysis of interspike intervals (ISI) was done to
      asses azimuth information in the firings of the neurons after the first spike.
      Thus latencies of simultaneously recorded single-unit (SU) spikes and local field
      potentials (LFP) in AI of cats were evaluated for sound presented from nine
      speakers arranged horizontally in the frontal half field in a semicircular array
      with a radius of 55 cm and the cat's head in the center. SU poststimulus time
      histograms (PSTH) were made for each speaker location for a 100-ms window after
      noise-burst onset using 1-ms bins. PSTH peak response latencies for SUs and LFPs
      decreased monotonically with intensity, and most of the change occurred within 15
      dB of the threshold at that particular azimuth. After correction for threshold
      differences, all latency-intensity functions had roughly the same shape,
      independent of sound azimuth. Differences with the minimum spike latency observed
      in an animal at each intensity were calculated for all azimuth-intensity
      combinations. This relative latency showed a weakly sigmoidal dependence on
      azimuth that was independent of intensity level >40 dB SPL. SU latency
      differences also were measured with respect to the latencies of the LFP triggers,
      simultaneously recorded on the same electrode. This difference was independent of
      stimulus intensity and showed a nearly linear dependence on sound azimuth. The
      mean differences across animals for both measures, however, were only significant
      between contralateral azimuths on one hand and frontal and ipsilateral azimuths
      on the other hand. Mean unit-LFP latency differences showed a monotonic
      dependence on azimuth with nearly constant variance and may provide the potential
      for an unbiased conversion of azimuth into neural firing times. The general trend
      for the modal ISI was the same as for relative spike latency: the shortest ISIs
      were found for contralateral azimuths (ISI usually 3 ms) and the longer ones for
      ipsilateral azimuths (the most frequent ISI was 4 ms, occasionally 5 ms was
      found). This trend was also independent of intensity level. This suggests that
      there is little extra information in the timing of extra spikes in addition to
      that found in the peak PSTH latency.

PMID- 9772269
TI  - Motor subcircuits mediating the control of movement velocity: a PET study.
AB  - The influence of changes in the mean velocity of movement on regional cerebral
      blood flow (rCBF) was studied using positron emission tomography (PET) in nine
      healthy right-handed adults while they performed a smooth pursuit visuomanual
      tracking task. Images of relative rCBF were obtained while subjects moved a hand
      held joystick to track the movement of a target at three different rates of a
      sinusoidal displacement (0.1, 0.4, and 0.7 Hz). Significant changes in rCBF
      between task conditions were detected using analysis of variance and weighted
      linear contrasts. The kinematics of arm and eye movements indicated that subjects
      performed tasks in a similar manner, particularly during the faster two tracking
      conditions. Significant increases in rCBF during arm movement (relative to an eye
      tracking only control condition) were detected in a widespread network of areas
      known for their involvement in motor control. The activated areas included
      primary sensorimotor (M1S1), dorsal and mesial premotor, and dorsal parietal
      cortices in the left hemisphere and to a lesser extent the sensorimotor and
      superior parietal cortices in the right hemisphere. Subcortically, activations
      were found in the left putamen, globus pallidus (GP), and thalamus, in the right
      basal ganglia, and in the right anterior cerebellum. Within the cerebral volume
      activated with movement, three areas had changes in rCBF that correlated
      positively with the rate of movement: left M1S1, left GP, and right anterior
      cerebellum. No movement-related sites had rCBF that correlated negatively with
      the rate of movement. Regressions of mean percent change (MPC) in rCBF onto mean
      hand velocity yielded two nonoverlapping subpopulations of movement-related loci,
      the three sites with significant rate effects and regression slopes steeper than
      0.17 MPC.cm-1.s-1 and all other sites with nonsignificant rate effects and
      regression slopes below 0.1 MPC.cm-1. s-1. Moreover, the effects of movement per
      se and of movement velocity varied in magnitude independently. These results
      confirm previous reports that movement-related activations of M1S1 and cerebellum
      are sensitive to movement frequency or some covarying parameter of movement. The
      activation of GP with increasing movement velocity, not described in previous
      functional-imaging studies, supports the hypothesis that the basal ganglia motor
      circuit may be involved preferentially in controlling or monitoring the scale
      and/or dynamics of arm movements. The remaining areas that were activated equally
      for all movement rates may be involved in controlling higher level aspects of
      motor control that are independent of movement dynamics.

PMID- 9772270
TI  - Changes in brain activity during motor learning measured with PET: effects of
      hand of performance and practice.
AB  - The aim of this study is to assess brain activity measured during continuous
      performance of design tracing tasks. Three issues were addressed: identification
      of brain areas involved in performing maze and square tracing tasks,
      investigation of differences and similarities in these areas related to dominant
      and nondominant hand performance, and most importantly, examination of the
      effects of practice in these areas. A total of 32 normal, right-handed subjects
      were instructed to move a pen with the dominant right hand (16 subjects) or
      nondominant left hand (16 subjects) continuously through cut-out maze and square
      patterns with their eyes closed during a 40-s positron emission tomography (PET)
      scan to measure regional blood flow. There were six conditions: 1) holding the
      pen on a writing tablet without moving it (rest condition); 2) tracing a maze
      without practice; 3) tracing the same maze after 10 min of practice; 4) tracing a
      novel maze; and tracing an easily learned square design at 5) high or 6) low
      speed. To identify brain areas generally related to continuous tracing, data
      analyses were performed on the combined data acquired during the five tracing
      scans minus rest conditions. Areas activated included: primary and secondary
      motor areas, somatosensory, parietal, and inferior frontal cortex, thalamus, and
      several cerebellar regions. Then comparisons were made between right- and left
      hand performance. There were no significant differences in performance. As for
      brain activations, only primary motor cortex and anterior cerebellum showed
      activations that switched with hand of performance. All other areas, with the
      exception of the midbrain, showed activations that were common for both right-
      and left-hand performance. These areas were further analyzed for significant
      conditional effects. We found patterns of activation related to velocity in the
      contralateral primary motor cortex, related to unskilled performance in right
      premotor and parietal areas and left cerebellum, related to skilled performance
      in supplementary motor area (SMA), and related to the level of capacity at which
      subjects were performing in left premotor cortex, ipsilateral anterior
      cerebellum, right posterior cerebellum and right dentate nucleus. These findings
      demonstrate two important principles: 1) practice produces a shift in activity
      from one set of areas to a different area and 2) practice-related activations
      appeared in the same hemisphere regardless of the hand used, suggesting that some
      of the areas related to maze learning must code information at an abstract level
      that is distinct from the motor performance of the task itself.

PMID- 9772271
TI  - Attenuation of delay-period activity of monkey prefrontal neurons by an alpha2
      adrenergic antagonist during an oculomotor delayed-response task.
AB  - To examine the role of norepinephrine receptors in spatial working memory
      processes mediated by the prefrontal cortex (PFC), noradrenergic antagonists
      (yohimbine for alpha2, prazosin for alpha1, and propranolol for beta receptors)
      were applied iontophoretically to neurons of the dorsolateral PFC in rhesus
      monkeys that performed an oculomotor delayed-response (ODR) task. The ODR task
      was initiated when the monkeys fixated on a central spot on a computer monitor
      and consisted of fixation (1 s), cue (1 of 4 peripheral cues, 0.5 s), delay
      (fixation cue only, 4 s), and go periods. In the go period, the subject made a
      memory-guided saccade to the target location that was cued before the delay
      period. I focused on 49 neurons that showed directional delay-period activity,
      i.e., a sustained increase in activity during the delay period, the magnitude of
      which varied significantly with the memorized target location. Iontophoretic
      (usually 50 nA) application of yohimbine, but not prazosin or propranolol,
      significantly decreased the activities of most of the neurons with directional
      delay-period activity (n = 41/49, 81%). Furthermore, yohimbine attenuated the
      sharpness of tuning, examined by a tuning index, of delay-period activity and had
      a greater attenuating effect on delay-period activity than on background
      activity. These findings suggest that the activation of alpha2-adrenergic
      receptors in the dorsolateral PFC plays a modulatory role in neuronal processes
      for visuospatial working memory.

PMID- 9772272
TI  - Effects of focal inactivation of dorsal or ventral layers of the lateral
      geniculate nucleus on cats' ability to see and fixate small targets.
AB  - To reveal contributions of different subdivisions of the lateral geniculate
      nucleus (LGN) to visuomotor behavior, segments of either layer A or the C layers
      were inactivated with microinjections of gamma-aminobutyric acid while cats made
      saccades to retinally stabilized spots of light placed either in affected regions
      of visual space or mirror-symmetric locations in the opposite hemifield.
      Inactivating layer A reduced the success rate for saccades to targets presented
      in affected locations from 82.4 to 26.8% while having no effect on saccades to
      the control hemifield. Saccades to affected sites had reduced accuracy and longer
      initiation latency and tended to be hypometric. In contrast, inactivating C
      layers did not affect performance. Data from all conditions fell along the same
      saccade velocity/amplitude function ("main sequence"), suggesting that LGN
      inactivations cause localization deficits, but do not interfere with saccade
      dynamics. Cerebral cortex is the only target of the A layers, so behavioral
      decrements caused by inactivating layer A must be related to changes in cortical
      activity. Inactivating layer A substantially reduces the activity of large
      subsets of corticotectal cells in areas 17 and 18, whereas few corticotectal
      cells depend on C layers for visually driven activity. The parallels between
      these behavioral and electrophysiological data along with the central role of the
      superior colliculus in saccadic eye movements suggests that the corticotectal
      pathway is involved in both deficits and remaining capacities resulting from
      blockade of layer A.

PMID- 9772273
TI  - alpha2-adrenoceptors modulate NMDA-evoked responses of neurons in superficial and
      deeper dorsal horn of the medulla.
AB  - Extracellular single unit recordings were made from neurons in the superficial
      and deeper dorsal horn of the medulla (trigeminal nucleus caudalis) in 21 male
      rats anesthetized with urethan. NMDA produced an antagonist-reversible excitation
      of 46 nociceptive as well as nonnociceptive neurons. Microiontophoretic
      application of a preferential alpha2-adrenoceptor (alpha2AR) agonist, (2-[2, 6
      dichloroaniline]-2-imidazoline) hydrochloride (clonidine), reduced the NMDA
      evoked responses of 86% (6/7) of nociceptive-specific (NS) neurons, 82% (9/11) of
      wide dynamic range (WDR) neurons, and 67% (4/6) of low-threshold (LT) neurons in
      the superficial dorsal horn. In the deeper dorsal horn, clonidine inhibited the
      NMDA-evoked responses of 94% (16/17) of NS and WDR neurons and 60% (3/5) of LT
      neurons. Clonidine facilitated the NMDA-evoked responses in 14% (1/17) of NS, 9%
      (1/11) of WDR, and 33% (2/6) of LT neurons in the superficial dorsal horn.
      Idazoxan, an alpha2AR antagonist, reversed the inhibitory effect of clonidine in
      90% (9/10) of neurons, whereas prazosin, an alpha1-adrenoceptor antagonist with
      affinity for alpha2BAR, and alpha2CAR, were ineffective. We suggest that
      activation of alpha2ARs produces a predominantly inhibitory modulation of the
      NMDA-evoked responses of nociceptive neurons in the medullary dorsal horn.

PMID- 9772274
TI  - Attention modulates both primary and second somatosensory cortical activities in
      humans: a magnetoencephalographic study.
AB  - To clarify the role of primary and second somatosensory cortex (SI and SII) in
      somatosensory discrimination, we recorded somatosensory evoked magnetic fields
      during a stimulus strength discrimination task. The temporal pattern of cortical
      activation was analyzed by dipole source model coregistered with magnetic
      resonance image. Stimulus intensity was represented in SI as early as 20 ms after
      the stimulus presentation. The later components of SI response (latency 37.7 and
      67.9 ms) were enhanced by rarely presented stimuli (stimulus deviancy) during
      passive and active attention. This supports an early haptic memory mechanism in
      human primary sensory cortex. Contra- and ipsilateral SII responses followed the
      SI responses (latency 124.6 and 138.3 ms, respectively) and were enhanced by
      attention more prominently than the SI responses. Active attention increased SII
      but not SI activity. These results are consistent with the concept of ventral
      somatosensory pathway that SI and SII are hierarchically organized for passive
      and active detection of discrete stimuli.

PMID- 9772275
TI  - Hypothesis for shared central processing of canal and otolith signals.
AB  - A common goal of the translational vestibuloocular reflex (TVOR) and the
      rotational vestibuloocular reflex (RVOR) is to stabilize visual targets on the
      retinae during head movement. However, these reflexes differ significantly in
      their dynamic characteristics at both sensory and motor levels, implying a
      requirement for different central processing of canal and otolith signals.
      Semicircular canal afferents carry a signal proportional to angular head
      velocity, whereas primary otolith afferents modulate approximately in phase with
      linear head acceleration. Behaviorally, the RVOR exhibits a robust response down
      to approximately 0.01 Hz, yet the TVOR is only significant above approximately
      0.5 Hz. Several hypotheses were proposed to address central processing in the
      TVOR pathways. All rely on a central filtering process that precedes a "neural
      integrator" shared with the RVOR. We propose an alternative hypothesis for the
      convergence of canal and otolith signals that does not impose the requirement for
      additional low-pass filters for the TVOR. The approach is demonstrated using an
      anatomically based, simple model structure that reproduces the general dynamic
      characteristics of the RVOR and TVOR at both ocular and central levels.
      Differential dynamic processing of otolith and canal signals is achieved by
      virtue of the location at which sensory information enters a shared but
      distributed neural integrator. As a result, only the RVOR is provided with
      compensation for the eye plant. Hence canal and otolith signals share a common
      central integrator, as in previous hypotheses. However, we propose that the
      required additional filtering of otolith signals is provided by the eye plant.

PMID- 9772276
TI  - GLC1A mutations point to regions of potential functional importance on the
      TIGR/MYOC protein.
AB  - PURPOSE: The aim of this study was to screen affected members of glaucoma
      families for mutations in the Trabecular Meshwork Inducible Glucocorticoid
      Response (TIGR) gene also known by the name myocilin (MYOC) or by combined names
      such as TIGR/MYOC. Our primary objectives were (1) to identify mutations
      responsible for glaucoma in members of three families for which we have shown
      linkage between chromosome 1 GLC1A-region markers and the primary open angle
      glaucoma (POAG) phenotype, and (2) to determine the relationship of these and
      other mutations to key points of predicted function and structure of the
      TIGR/MYOC protein. METHODS: DNA sequence determination was used to identify
      sequence changes in sections of the TIGR/MYOC gene that were PCR-amplified from
      genomic DNA from the probands of three previously-reported GLC1A juvenile-onset
      POAG families, UM:JG1, UM:JG3, UM:GL57, and unmapped family UM:JG5. Allele
      specific oligonucleotide hybridization was used to screen for the identified
      mutations in PCR-amplified DNA from individual members of each pedigree and from
      a panel of 11 additional juvenile glaucoma family probands, 42 adult POAG family
      probands, and 43 normal individuals. Computerized algorithms were used to
      identify functional motifs and predict structures of normal and mutant forms of
      the protein. RESULTS: Sequence changes were found that alter amino acids in the
      olfactomedin-like domain near the carboxy terminal end of the TIGR protein in
      affected members of families UM:JG1 (Pro370Leu), UM:JG3 (Val426Phe), UM:GL57
      (Glu323Lys) and UM:JG5 (Gly252Arg). Co-segregation of glaucoma and Pro370Leu,
      Val426Phe, and Gly252Arg in known GLC1A families suggests that these are
      mutations. Although the Gly252Arg substitution observed in UM:JG5 is non
      conservative, it was not possible to distinguish whether it is a mutation or a
      polymorphism. None of the sequence changes described in these families were
      observed in other juvenile glaucoma cases in this study, nor in any of the POAG
      or phenotypically normal individuals tested here. Analysis of amino acid sequence
      changes resulting from mutations described in this and other works demonstrate
      localization of many mutations in the vicinity of predicted functional motifs in
      the olfactomedin-like domain. Identification of rat latrophilin (LPH1/CIRL) as a
      new member of the olfactomedin-like protein family to which TIGR/MYOC belongs
      suggests that the region of olfactomedin homology is a protein domain that can
      occur in different protein contexts. CONCLUSIONS: Location of mutations described
      in this and previous work suggests that some specific predicted protein motifs in
      the olfactomedin-like domain may be important to TIGR/MYOC function. In some
      cases, the role of TIGR/MYOC in the etiology of glaucoma may result from
      alteration of the sequences recognized by modifying enzymes such as casein kinase
      II. In other cases altered protein folding may affect access of enzymes to their
      target sequences on TIGR/MYOC. Although modifications and structures discussed
      here are predicted rather than proven, they provide a useful theoretical
      framework for design of subsequent experiments. Alterations to protein folding
      and predicted modification motifs cannot explain the pathogenic mechanisms of all
      of the known TIGR/MYOC glaucoma mutations.

PMID- 9772277
TI  - Multifunctional potential of the plasminogen activation system in tumor invasion
      and metastasis (review).
AB  - Tumor cell migration and invasion into the surrounding tissue depend on the
      invasive capacity of cells leading to the loosening of cell-cell and cell
      substratum contacts via cell surface associated proteolytic enzyme systems.
      Plasmin is one of the enzymes involved in these complex events. It is generated
      by the cleavage of the proenzyme plasminogen upon the action of the urokinase
      type plasminogen activator (uPA). uPA is synthesized and secreted by tumor cells
      and normal cells and interacts with a specific cell surface receptor (uPAR)
      thereby focalizing enzymatic activity to the cell surface. The activity of uPA is
      controlled by plasminogen activator inhibitors type-1 and type-2. A strong
      statistically independent prognostic impact has been attributed to uPA and its
      inhibitor PAI-1 in a variety of malignancies. Besides its proteolytic activity,
      uPA in concert with uPAR exert biological effects characteristic for molecules
      with signal transducing properties including chemotaxis, migration/invasion,
      adhesion, and mitogenesis.

PMID- 9772278
TI  - Transcriptional activation of functional endogenous estrogen receptor gene
      expression in MCF10AT cells: a model for early breast cancer.
AB  - Utilizing the MCF10AT xenograft model for progression of human proliferative
      breast disease, we detected expression of the endogenous estrogen receptor (ER)
      gene only in MCF10AneoT and cells of the MCF10AT system, all of which stably
      express a transfected mutated T24 Ha-ras gene. ER transcripts were undetectable
      in the parental MCF10A cells and in MCF10A cells transfected with normal c-Ha-ras
      or vector. ER transcripts expressed in MCF10AT cells contain a normal full-length
      ER coding region and direct synthesis of a normally sized ER protein. The protein
      is functional based on its ability to mediate estradiol (E2)-induced increases of
      transcription from both endogenous and exogenous E2-regulated genes.
      Transcriptional activation of the endogenous ER gene does not appear to be
      related to a change in methylation status of the gene since a diagnostic CpG site
      in exon 1 that is methylated in ER-negative breast tumors and completely
      unmethylated in ER-positive breast tumors is hypomethylated to the same extent in
      ER-negative MCF10A cells and ER-positive MCF10AT cells. E2 increased both the
      number and size of soft-agar colonies formed by MCF10AT3c cells, a line from a
      third generation MCF10AT xenograft lesion. This suggests that xenograft passage
      has selected for growth regulatory pathways that are E2-responsive and that
      identification of these pathways and their role in progression will aid in
      determining how E2 acts to increase risk of breast cancer.

PMID- 9772279
TI  - Genetic background influences timing, morphology and dissemination of lymphomas
      in p53-deficient mice.
AB  - To examine the influence of genetic background on tumorigenesis in p53-deficient
      mice, we used selective breeding to produce congenic mice with a null p53 gene
      mutation introduced into the VM inbred strain. Cohorts of homozygous p53 null (-/
      ) mice from the original C57B6/129Sv mixed strain and the VM congenic strain were
      monitored for spontaneous tumor development, as were control cohorts of wild-type
      (+/+) and heterozygous (+/-) animals. Twenty-six of 28 C57B6/129Sv (-/-) mice
      died by the study end date (median survival =184.5 days). Twenty-three of 26 VM (
      /-) mice died and their survival was significantly shorter (111 days, P<0.0001).
      Of 26 C57B6/129Sv (-/-) mice that died, 21 were autopsied: all 21 had lymphomas.
      Of 26 VM mice that died (23 -/-, 3 +/-), 21 were autopsied: 19 developed lymphoma
      and two had sarcomas. Several mice had additional neoplasms. Lymphomas in VM mice
      were distinct from those in C57B6/129Sv mice in that they i) arose on average
      more than two months earlier, ii) involved thymus more often than spleen or lymph
      nodes and iii) were more often poorly differentiated, high grade tumors. These
      results demonstrate that genetic background alone influences the onset,
      morphology and dissemination of lymphomas in p53-deficient mice and suggest the
      presence of genes which modify the timing and biological nature of lymphomas in
      these mice.

PMID- 9772280
TI  - Reduction of telomeric signals in murine melanoma and human breast cancer cell
      lines treated with 3'-azido-2'-3'-dideoxythymidine.
AB  - The purpose of this study was to determine, using fluorescence in situ
      hybridization (FISH), whether treatment of cancer cells with 3'-azido-2'-3'
      dideoxythymidine (AZT) has any effect on telomere length as determined by the
      telomeric signal intensity. To do so, we treated a metastatic murine melanoma
      cell line (K-1735 clone X-21) and a human breast cancer cell line (MCF-7) with
      three concentrations of AZT for 72 h at 37uC. FISH preparations processed using
      an all-human telomeric DNA probe showed a significantly reduced, concentration
      dependent telomeric signal intensity in interphase and metaphase spreads of AZT
      treated cells as compared with the signal intensity in untreated controls, which
      showed no reduction. We conclude from these preliminary results that AZT has the
      potential of targeting the telomeric ends of chromosomes in cancer cells and
      promoting cell death and could well be tested along with other chemotherapy drugs
      given to cancer patients for this purpose.

PMID- 9772281
TI  - Expression of c-MET/HGF receptor mRNA and protein in human non-malignant and
      malignant prostate tissues.
AB  - We previously reported the expression of hepatocyte growth factor (HGF), a ligand
      for c-MET, at the level of mRNA and protein in human prostate tissues. The
      present study was carried out to evaluate the relationship between c-MET
      expression and cancer cell proliferation or effect of cancer therapy. The
      expression both in mRNA and protein levels of c-MET proto-oncogene was determined
      semi-quantitatively by reverse transcription-competitive polymerase chain
      reaction (RT-competitive PCR) and Western blot analysis for prostate tissues from
      32 Japanese male subjects. In addition, tissue localization of c-MET translation
      product was examined by immunohistochemistry for corresponding specimens.
      Although there was significantly higher c-MET protein expression in malignant
      (prostate cancer treated with/without neoadjuvant endocrine therapy) than in non
      malignant prostate tissues (normal prostate and benign prostate hyperplasia;
      BPH), unexpectedly, c-MET mRNA showed high expression in the non-malignant group.
      Thus, there was no parallelism between mRNA and protein expressions of c-MET.
      Endocrine therapy did not alter c-MET mRNA and protein expressions in human
      prostate cancer. Immunohistochemical localization and expression of c-MET protein
      was found to be intense in cancer cells and weak in epithelia of normal and
      hyperplastic prostates. Unconcerted expression of mRNA and protein of c-MET, the
      reason of which is uninterpretable, is supposed to be one of characteristics of
      human prostate cancer.

PMID- 9772282
TI  - Expression of cell adhesion molecule CD44 and sialyl Lewis A in gastric carcinoma
      and colorectal carcinoma in association with hepatic metastasis.
AB  - To clarify the role of the expression of adhesive molecules [CD44 (standard form)
      and sialyl Lewis A (sialyl Lea)] on hepatic metastasis, 108 advanced gastric
      carcinomas and 94 advanced colorectal carcinomas were investigated
      immunohistochemically. Multivariate analysis demonstrated that CD44 expression
      and lymph node metastasis in gastric cancer and CD44 and sialyl Lea expression in
      colorectal cancer were significantly related to hepatic metastasis. The incidence
      of hepatic metastasis was highest in patients with the expression of both CD44
      and sialyl Lea. The expression of CD44 standard form as well as sialyl Lea may
      have a major role as adhesion molecules in the process of hepatic metastasis.

PMID- 9772283
TI  - Effects of all-trans retinoic acid and interferon alpha in peripheral
      neuroectodermal tumor cell cultures and xenografts.
AB  - Peripheral neuroectodermal tumors (PNET) have an unsatisfactory outcome when
      treated with standard approaches. Among novel treatments, the use of biological
      response modifiers has rarely been reported in this group of malignancies. We
      have previously demonstrated that both all-trans retinoic acid (ATRA) and
      interferon a (IFNa) can inhibit proliferation of human PNET cells and that ATRA
      can up-regulate IFNa receptor expression in vitro. In this study we evaluated the
      anti-tumor effects of ATRA and IFNa in PNET cells in vitro and in a human PNET
      xenograft model, using CHP100 cells. A synergistic inhibitory effect of ATRA and
      IFNa was observed on CHP100 cells in vitro. On the contrary, a significant
      inhibition of tumor growth was observed in mice treated with ATRA alone, whereas
      neither IFNa nor the combination of ATRA and IFNa, reached a statistically
      significant anti-tumor effect. Histologic examination of tumors revealed the
      presence of necrosis upon treatment with IFNa, whereas almost no necrosis, but a
      more differentiated morphology, confirmed by electron microscopy analysis, was
      associated with the ATRA containing treatments. Taken together these data show an
      in vitro and in vivo anti-tumor activity of ATRA in human PNET cells, although no
      synergism of ATRA and IFNa was observed in our xenograft model.

PMID- 9772285
TI  - Specific induction of hepatocellular adenomas by transplacental administration of
      ENU in the tsc2 gene mutant (Eker) rat.
AB  - Eker rats develop dominantly inherited renal carcinomas (RCs), with hereditary
      mutation, and following somatic mutation (Knudson's second hit) at tuberous
      sclerosis gene (Tsc2). We document the effect of transplacental administration of
      N-ethyl-N-nitrosourea to Eker (Eker/+) and non-Eker (+/+) rats (same genetic
      background). Although we observed no difference in the number of preneoplastic
      GST-P positive foci between Eker and non-Eker rats, interestingly we observed the
      specific development of hepatocellular adenomas only in Eker rats. The Tsc2 gene
      mutation might thus influence the phenotype of preneoplastic initiated
      hepatocytes.

PMID- 9772284
TI  - Expression profile of senescence-associated beta-galactosidase and activation of
      telomerase in human ovarian surface epithelial cells undergoing immortalization.
AB  - Senescence is a specific physiological stage of cells characterized by long
      population doubling time. It accounts for the inability of normal somatic cells
      to undergo indefinite cell division. As the number of population doublings
      increase, cell cycle regulatory mechanisms come into play and signal cells to
      exit the cell cycle and become senescent. Senescence has been implicated in the
      aging process and may function as a tumor suppressor mechanism in human cells.
      The ability to measure the degree of cellular senescence is important in
      understanding the biological processes regulating cell aging and immortalization.
      Senescent cells exhibit an enzyme termed senescence-associated histochemical
      staining. Cells immortalized by viral oncogenes often enter a stage of crisis at
      the early phase of immortalization. The cells at crisis have a long population
      doubling time. Cells at the crisis stage resemble senescent cells and the
      expression of SA- beta-Gal may be used to monitor the process of immortalization.
      In this study the expression profile of SA-beta-Gal was examined in human ovarian
      surface epithelial cells (HOSE 6-3) undergoing immortalization by the human
      papilloma viral oncogene E6 and E7 (HPV E6 and E7). Our results showed a low
      percentage (12.0%) of HOSE 6-3 cells expressing SA-beta-Gal activity at the pre
      crisis stage. The percentage of HOSE 6-3 cells expressing SA-beta-Gal activity
      was highest (39.2%) at the crisis stage. When HOSE 6-3 cells achieved
      immortalized status there was a sharp decrease in cells (1. 3%) expressing SA
      beta-Gal activity. In addition, an inverse relationship between the expression of
      SA-beta-Gal activity and telomerase activity was noted in cells undergoing
      immortalization. The results confirm that the SA-beta-Gal enzyme is a good marker
      for monitoring the population of cells undergoing senescence at different stages
      of immortalization and that telomerase activation is a characteristic feature of
      post-crisis cells.

PMID- 9772286
TI  - Differential polymerase chain reaction: a technical comparison of three methods
      for the detection of CDK4 gene amplification in glioblastomas.
AB  - Among the different techniques used to detect oncogene amplification in tumor
      DNA, Southern blot and differential PCR have been the most frequently used. We
      report on a technical comparison of three different methods to detect gene
      amplification by differential PCR: ethidium bromide staining, silver staining
      (both after standard differential PCR), and fluorescent differential PCR. We
      explored the relative densitometric measure of a 119 bp fragment of the CDK4 gene
      versus an 82 bp fragment of the IFNG gene. In total agreement with previous
      studies carried out by Southern blot and differential PCR by other authors, we
      were able to detect CDK4 amplification in 3 of the 21 glioblastomas (14%), but
      only by the fluorescent differential PCR method. In conclusion, fluorescent
      differential PCR is more sensitive than standard differential PCR for detection
      oncogene amplification in tumor DNAs.

PMID- 9772287
TI  - Brain-specific angiogenesis inhibitor 1 expression is inversely correlated with
      vascularity and distant metastasis of colorectal cancer.
AB  - Brain-specific angiogenesis inhibitor (BAI) 1 was recently isolated as a novel
      p53 inducible gene. BAI1 has been suggested to play a significant role in
      angiostasis. We studied the expression of BAI1 in 49 colorectal cancer specimens
      by RT-PCR. BAI1 expression was significantly reduced in colorectal cancers as
      compared to the extraneoplastic tissues (X(2) test, p=0.041). BAI1 expression was
      inversely correlated with vascular invasion and metastasis (Fisher's exact test,
      p 0.045). Moreover, vascularity in the colorectal cancer was inversely correlated
      with BAI1 gene expression (Mann-Whitney U-test, p=0.0003). These observations
      suggested that BAI1 expression might inhibit angiogenesis and metastasis of
      colorectal cancer.

PMID- 9772288
TI  - Detection of a rare point mutation at codon 59 and relatively high incidence of H
      ras mutation in Indian oral cancer.
AB  - Analysis of H-, K- and N-ras genes for point mutations by PCR-SSCP and direct
      sequencing of 46 oral SCCs that were previously analyzed for p53 mutations
      revealed that 9 (20%) had point mutations in either the H-ras or the N-ras. A
      novel mutation at codon 59 (GCC-ACC) of H-ras thus far reported only in v-H-ras
      of Harvey murine sarcoma virus was observed in a tumor of the cheek. Majority
      (8/9) of these mutations were observed in H-ras, one in N-ras and none in K-ras.
      This study indicated that the ras gene mutation was relatively high in oral
      cancers associated with tobacco chewing and the ras and p53 mutational events
      seem to be independent and mutually exclusive.

PMID- 9772289
TI  - Expression of platelet-derived endothelial cell growth factor in non-small cell
      lung carcinomas: relationship to various biological factors.
AB  - The expression of platelet-derived endothelial cell growth factor (PD-ECGF) was
      determined immunohistochemically in 143 non-small cell lung carcinomas. Staining
      was observed in 48% of the cases. A relationship between histology, stage, erbB
      1, erbB-2, ras and PD-ECGF expression was not found. A relationship of borderline
      significance was observed between PD-ECGF and p53 expression. There was also no
      relationship between PD-ECGF expression and proliferative activity (G1 phases, S
      phases, cyclin A). In contrast, a correlation between PD-ECGF- and VEGF
      expression was detectable (p=0.009). Furthermore, PD-ECGF expression was related
      to the response of lung carcinomas to doxorubicin (p=0.0004). Of 35 sensitive
      tumors, 26 carcinomas were PD-ECGF-positive (74%) while of 108 resistant
      carcinomas only 43 tumors (40%) exhibited PD-ECGF expression.

PMID- 9772290
TI  - Inhibitory effects of an antiestrogen, toremifene, on the phorbol ester-induced
      adhesive capacity of breast carcinoma cells.
AB  - Previous studies have revealed that protein kinase C (PKC) is responsible for
      malignant progression. In the present study, we investigated the potent
      inhibitory effects of an antiestrogen, toremifene, on PKC-mediated cellular
      adhesion. A phorbol ester, phorbol 12-myristate 13-acetate (PMA), significantly
      enhanced alpha2beta1 integrin-dependent adhesion of MCF-7 breast carcinoma cells.
      This PMA-induced adhesion was partially inhibited by incubating cells with
      toremifene prior to PMA exposure in a time- and dose-dependent manner. FACS
      analysis demonstrated that the PMA-induced alpha2beta1-dependent cellular
      adhesion was accompanied with elevated expression of alpha2beta1+integrin subunit
      on the cell surface. However, toremifene did not affect the elevated expression
      levels of these integrins but rather the avidity of alpha2beta1 integrin. We
      concluded that toremifene inhibited cellular adhesion activated by PMA, probably
      through mechanism which inhibits PKC.

PMID- 9772291
TI  - Cisplatin and phorbol ester independently induce ERCC-1 protein in human ovarian
      carcinoma cells.
AB  - Nucleotide excision repair (NER) is the DNA repair pathway by which cisplatin
      induced damage is removed from DNA in human cells. ERCC-1 is one of the essential
      proteins in NER, and is essential for life. Enhanced ERCC-1 expression has been
      associated with clinical and cellular resistance to cisplatin. We therefore
      carried out this study to investigate the effect of cisplatin on ERCC-1 protein
      expression in A2780/CP70 human ovarian cancer cells. Western blot analysis showed
      that ERCC-1 protein levels were increased to more than 3 times control after a 1
      h cisplatin exposure to A2780/CP70 cells in culture. This increase was time- and
      concentration-dependent. The effect of cisplatin was maximal at 40 mM and peaked
      24-48 h after exposure to the drug. These results extend our previous
      observations that ERCC-1 mRNA expression is induced by cisplatin in this system.
      TPA, a known AP-1 activator and tumor-promoting phorbol ester, also induced ERCC
      1 protein to the same extent as cisplatin, but did not synergize with cisplatin
      in this regard. These findings suggest that ERCC-1 gene up-regulation in these
      cells can result through a DNA damage-response pathway, or through the induction
      of AP-1 activity, independent of the occurrence of DNA damage.

PMID- 9772292
TI  - Polyamine metabolism as target for cancer chemoprevention (review).
AB  - The natural polyamines putrescine, spermidine and spermine are intimately
      involved in growth-related processes. More and more evidence indicates that the
      excessive accumulation of putrescine and spermidine favors malignant
      transformation of cells. Selective depletion of putrescine has been shown to
      restore in some transformed cells the normal phenotype. Inhibition of polyamine
      formation appears, therefore, a rational target in chemoprevention. Clinical
      trials with 2-(difluoromethyl)ornithine, a selective inactivator of ornithine
      decarboxylase, a key enzyme of polyamine biosynthesis, are promising. Structural
      analogs of the polyamines with polyamine-mimetic or antagonist properties, and
      calmodulin antagonists are other types of drugs which affect several key
      reactions of polyamine metabolism, and appear to be candidates for the prevention
      of carcinogenesis especially of the gastrointestinal tract.

PMID- 9772294
TI  - Low MIB-1 labeling index in anti-HCV positive hepatocellular carcinoma.
AB  - It has been reported that hepatitis C virus-related hepatocellular carcinoma
      (HCC) patients survive longer than hepatitis B virus-related patients. In this
      study, since HCC patients positive for anti-HCV antibody had significantly longer
      disease-free survival (p<0.05), we evaluated the proliferative activity of 58
      resected HCCs and the status of their viral infections. Ki-67 (MIB-1)
      immunostaining, argyrophilic nucleolar organizer regions and c-myc gene
      amplification were examined as parameters of proliferation, and p53
      overexpression was examined in relation to clinicopathologic features and
      prognosis. Thirty-nine patients with HCC (67%) were positive for anti-HCV
      antibody alone, five (9%) were negative for both anti-HCV and HBV antibodies, two
      (3%) were positive for both anti-HCV and HBV antibodies, and 12 (21%) had HBsAg
      alone. HCC patients with anti-HCV antibody had a lower MIB-1 labeling index (LI)
      than HCC patients negative for the antibody (p<0.05), irrespective of the serum
      HBsAg status. However, there was no significant correlation between anti-HCV
      antibody and other proliferative parameters. MIB-1 could simply be related to
      cellular proliferation. On the other hand, the other parameters may be related to
      tumor progression as well as proliferation. HCV-related HCC does have lower
      proliferative activity and a better prognosis.

PMID- 9772293
TI  - Cell cycle arrest in ovarian cancer cell lines does not depend on p53 status upon
      treatment with cytostatic drugs.
AB  - Human ovarian cancer cell lines with different p53 status were investigated for
      p53-dependency of cell cycle arrest upon treatment with cytostatic drugs. For
      this purpose commonly used anti-cancer drugs and a novel anti-cancer drug,
      gemcitabine, were applied. Cell cycle arrest was dependent on the drug dose used,
      as observed for all anti-cancer drugs applied, but not related to functional p53.
      With the exception of the etoposide-effected G2/M arrest at high concentrations,
      which seems to depend on functional p53, since it did not occur in cells with
      inactive p53. Only in cells with wt p53 and quasi-wild-type, p53 accumulated in
      the nucleus upon drug treatment with all anti-cancer agents applied. The level of
      accumulation was drug dose-dependent for each drug tested. The accumulated p53
      was biochemically active, as measured in a transient transfection assay upon
      treatment with gemcitabine, cisplatin, etoposide, and Taxol. Activity was
      dependent on the drug dose applied and proportional to the level of accumulated
      p53, except for Taxol-induced p53 accumulation which correlated inversely with
      p53 biochemical activity. Apoptosis was estimated by in situ end labeling by
      biotinylated dUTP with the terminal deoxyribonucleotidyl transferase assay.
      Apoptosis occured after arrest at the various phases of the cell cycle in all
      cell lines tested, depending on the drug and the drug dose used. Nevertheless,
      cells with wt p53 exhibited the highest fraction of apoptotic cells.

PMID- 9772295
TI  - Prediction of toxicity but not of clinical course by determining carboplatin
      exposure in patients with epithelial ovarian cancer treated with a combination of
      carboplatin and cisplatin.
AB  - We present the data from 105 patients with primary epithelial ovarian cancer, who
      received up to 6 cycles of carboplatin (300 mg/m2) and cisplatin (100 mg/m2) as
      one treatment arm of a prospective randomized trial. Values for first-course
      carboplatin area-under-the-curve (AUC) were determined retrospectively. WHO grade
      3-4 thrombocytopenia was found in 10% of patients with low AUC (AUC <4 mg/ml x
      min), but in 44.6% of patients with high AUC (AUC 4 mg/ml x min) (chi-square
      p<0.0001). No single case of ototoxicity was found in the low AUC group but in
      12% of patients in the high AUC group (chi-square p=0.003). Determination of
      carboplatin AUC may prevent ototoxicity and severe thrombocytopenia for the first
      cycle of combined treatment with carboplatin and cisplatin.

PMID- 9772296
TI  - Matrix metalloproteinase matrilysin (MMP-7) participates in the progression of
      human gastric and esophageal cancers.
AB  - Matrilysin is one of matrix metalloproteinases, which is supposed to have a
      specific role in tumor progression. Expression of matrilysin was investigated in
      gastric and esophageal cancers by an immunohistochemical examination. Matrilysin
      was expressed in all esophageal squamous cell carcinomas (13/13) and in the
      majority of gastric adenocarcinomas (31/35, 89%). The positive staining was
      observed in tumor cells of cancerous tissues. In gastric cancers, there were
      significant statistical correlations between matrilysin expression at the
      invasive front and nodal metastasis or advanced stage. These results suggest that
      overexpression of matrilysin has an important role in the progression of upper
      gastrointestinal cancers.

PMID- 9772297
TI  - Combined effect of chemopreventive agent N-(4-hydroxyphenyl) retinamide (4-HPR)
      and gamma-radiation on bladder cancer cell lines.
AB  - The incidence of bladder cancer has increased in the United States during the
      past 50 years, consistent with increased exposure to bladder carcinogens in the
      environment and tobacco use. Although N-(4-hydroxyphenyl) retinamide (4-HPR), a
      retinoid derivative, has been used as a chemopreventive agent of bladder cancer
      in clinical trials, little is known about its mechanisms of action against
      bladder cancer cells. Previous studies suggest this chemopreventive agent may
      inhibit tumor growth by inducing apoptosis. To further investigate this putative
      effect, we examined the effect of 4-HPR and gamma-radiation and their combined
      effects in three selected bladder cancer cell lines. Indeed, 4-HPR induced
      apoptosis in these cell lines in a dose-dependent manner. A 2.5 microM dose of 4
      HPR and 50 rad of gamma-irradiation induced about 10% increase in apoptotic
      cells, respectively. However, this low dose 4-HPR combined with low dose gamma
      irradiation had a synergistic effect on apoptosis, in which apoptotic cells
      increased by more than 30%. The findings have potential clinical implications and
      warrant further investigations both in vitro and in vivo in bladder cancer.

PMID- 9772298
TI  - Effect of oncogene expression on telomerase activation and telomere length in
      human endothelial, fibroblast and prostate epithelial cells.
AB  - Although strong evidence is mounting that telomerase reactivation and the thereof
      resulting stabilization of telomeres is a major mechanism for human cells to
      overcome replicative senescence, a causal relationship linking telomerase
      activation conclusively to tumorigenesis remains to be established. Thus, the
      possibility exists that telomerase activation is passively co-selected as tumors
      develop. To elucidate the function of telomerase during tumorigenesis, we
      followed telomerase reactivation during immortalization of human primary cell
      types with in vitro transforming agents and determined the tumorigenic potential
      of these cells at various stages of transformation. The effects of SV40, v-Ki
      ras, HPV-18 and HPV-16 E6/E7 oncoproteins on telomerase expression was examined
      in primary and immortalized human prostate epithelial (HPE), human prostate
      fibroblast (HPF), and umbilical vein endothelial cells (HUVEC). All of five SV40
      transformed HPE and HPF lines were telomerase positive and had shorter telomeres
      than primary cells. The two HPV-18 immortalized HPE cell lines also expressed
      telomerase activity. In contrast, E6 or E7 alone could not produce immortalized
      HUVEC and did not reactivate telomerase. Life-span, however, was extended. The
      E6/E7 immortalized HUVEC had telomerase activity and short but stable telomeres.
      HPE, HPF or HUVEC cells which had been transformed by one oncoprotein alone were
      not tumorigenic although they had overcome cellular senescence and re-activated
      telomerase. However, if these cells were transformed by a second agent, either
      infection with v-Ki-ras or X-ray treatment, they were able to form tumors in nude
      mice. This suggests that tumorigenesis is a multistep process and that telomerase
      activation alone is not sufficient for malignant transformation in human cells.

PMID- 9772299
TI  - Neuroimmunoregulation and cancer (review).
AB  - It is certain that neuroimmune mechanisms play a role in host defence against
      cancer. However, this interaction is highly complex and many variations are
      possible according to the nature of the neoplasms involved. There are indications
      that adaptive immunity is present in a significant proportion of tumor bearing
      hosts, and this defence may be boosted by specially designed vaccines and
      cytokines. Natural immune mediators are also implicated in resistance against
      tumor development. Here we review the evidence suggesting that hormonal
      manipulation of the host can result in the elevation of immune defences against
      cancer. Such manipulation strengthens both the adaptive and natural immune
      defences of the host, both of which play significant roles. Natural defence
      mechanisms are boosted by cytokines and hormones during febrile reactions which
      are now known as the acute phase response. It is suggested that hormonal
      stimulation of immune mechanisms coupled with the usual immunostimulants already
      in use may be employed to good advantage for the combination immunotherapy of
      cancer. Modern molecular biology approaches permit the development of laboratory
      monitoring procedures which may be used for the prediction and follow-up of
      therapeutic success.

PMID- 9772300
TI  - NRG-3 in human breast cancers: activation of multiple erbB family proteins.
AB  - Ligands of the EGF/Heregulin family control the growth of epithelial cells by
      binding to receptors of the erbB family. By searching a large database of cDNA
      sequences at Human Genome Sciences Inc. we have identified a new encoded protein
      sequence containing all the conserved elements of the EGF/Heregulin family. The
      same sequence has recently been independently identified as NRG-3. The EGF-like
      domain of NRG-3 was generated as a recombinant protein in E. coli and used to
      test the specificity of receptor binding. In human breast cancer cells and in 32D
      cells transfected by erbB family members, NRG-3 activated multiple erbB family
      members. These include EGF receptor (erbB1) and erbB4 when expressed individually
      and erbB2 and erbB3 when expressed together. Recombinant NRG-3 altered the growth
      of human breast cancer cells growing in vitro. NRG-3 was expressed in cell lines
      derived from breast cancer. These results indicate that NRG-3 is a potential
      regulator of normal and malignant breast epithelial cells in vivo.

PMID- 9772301
TI  - Enhancement of all-trans-retinoic acid efficiency in granulocytic differentiation
      of HL-60 cells by incorporation into low density lipoprotein.
AB  - All-trans-retinoic acid (ATRA) has been proven to lead to complete remission of
      acute promyelocytic leukemia by inducing differentiation into granulocytes except
      when an acquired resistance occurred. High levels of low density lipoprotein
      (LDL) receptor in cancer cells suggested the use of ATRA incorporated into LDL.
      50% of HL-60 cell differentiation were obtained with 5 nmoles/l of ATRA-LDL
      compared to 150 moles/l of ATRA. Maximal differentiation (80%) was reached at 25
      nmoles/l and 1,000 nmoles/l respectively. This higher efficiency suggests the
      involvement of LDL receptor in ATRA-LDL internalization and/or the protection of
      the drug, from eventual catabolism, by LDL particles.

PMID- 9772302
TI  - Association of PTPmu with catenins in cancer cells: a possible role for E
      cadherin.
AB  - Protein tyrosine phosphorylation and dephosphorylation is regulated by the action
      of protein tyrosine kinases (PTK) and phosphatases (PTP) respectively. The
      receptor type phosphatase, PTPmu, is located at the cell surface where it may
      function to regulate the phosphoryl status of members of the cadherin adhesion
      complex and thus cadherin function. We have investigated the association of PTPmu
      with E-cadherin and catenin molecules in human tumour cells and report that
      PTPmu; is associated with E-cadherin and alpha and beta-catenin in E-cadherin
      positive cell lines. However, no association between PTPmu and catenin members
      could be detected in E-cadherin negative cells. These observations suggest that
      the association of PTPmu with catenin molecules may occur via E-cadherin rather
      than a direct interaction.

PMID- 9772303
TI  - Up-regulation of p53 by antisense expression of HPV18 E6 oncogene does not
      influence the level of MN/CA IX tumor-associated protein in HeLa cervical
      carcinoma cells.
AB  - Oncogenic potential of human papillomaviruses is related to capacity of HPV
      encoded oncoproteins to bind and inactivate tumor suppressor proteins.
      Interaction of p53 with HPV E6 results in aberrant regulation of various cellular
      genes. We evaluated the possible involvement of MN/CA9 gene, whose expression is
      closely associated with cervical carcinomas, in regulatory pathways driven by p53
      and E6. We demonstrated that one of the two p53 consensus sequences present in
      MN/CA9 promoter participates in DNA-protein interaction but it does not bind p53.
      Tetracycline-inducible antisense expression of HPV18 E6 in human cervical
      carcinoma HeLa cells resulted in increased level of p53 but did not affect
      expression of MN/CA IX protein. Therefore we conclude that at least in HeLa cells
      there is no direct relationship between expression of MN/CA IX and expression of
      E6 or p53.

PMID- 9772304
TI  - Accumulation of albumin in renal cytosol of hamsters treated with estradiol and
      in estrogen-induced hamster kidney tumors.
AB  - The intracellular accumulation of albumin has been observed in cytosols of benign
      and malignant human breast tumors and in mammary tumors of rodents induced by
      carcinogens. Additionally, cellular uptake of albumin has been detected in MCF-7
      human breast cancer cells in culture. The clinical relevance of the albumin
      accumulation in human and rodent mammary tumors is not clear. In this study, we
      investigated the accumulation of albumin in an estrogen-induced and -dependent
      hamster kidney tumor model to understand the mechanisms and the role of hormones
      in this process. Protein accumulation patterns were examined by Western blot
      analyses in kidney homogenates of hamsters treated with 17beta-estradiol for
      various lengths of time and in kidney tumors which are induced with 100%
      incidence by this treatment for at least six months. Such analyses were also
      carried out in tissues of hamsters treated with the weakly carcinogenic estrogen
      17alpha-ethinylestradiol (10% tumor incidence after nine months of treatment).
      Our data demonstrate the accumulation of albumin in kidney of hamsters treated
      with 17beta-estradiol but not with 17alpha-ethinylestradiol. Albumin accumulates
      specifically in the target organ of carcinogenesis, the kidney, however, with no
      increase in the serum concentrations or in the liver. Tumors do not develop in
      the livers of hamsters under these conditions of 17beta-estradiol treatment. This
      accumulation of albumin in hamster kidney may be the result of damage to the
      glomerulum which may be compromised by estradiol-induced toxicity and therefore
      unable to filter out excess albumin.

PMID- 9772307
TI  - Patient compliance in the use of Vivotif Berna(R) vaccine, typhoid vaccine, live
      oral Ty21a.

PMID- 9772305
TI  - Evaluation of radiation effects against C6 glioma in combination with vaccinia
      virus-p53 gene therapy.
AB  - The primary objective of this study was to evaluate the antitumor effects of
      recombinant vaccinia virus-p53 (rVV-p53) in combination with radiation therapy
      against the C6 rat glioma, a p53 deficient tumor that is relatively
      radioresistant. VV-LIVP, the parental virus (Lister strain), was used as a
      control. Localized treatment of subcutaneous C6 tumors in athymic mice with
      either rVV-p53 or VV-LIVP together with tumor irradiation resulted in low tumor
      incidence and significantly slower tumor progression compared to the agents given
      as single modalities. Assays of blood and spleen indicated that immune system
      activation may account, at least partly, for the enhance tumor inhibition seen
      with combined treatment. No overt signs of treatment-related toxicity were noted.

PMID- 9772308
TI  - Primary health care needs for travel medicine training in Britain.
AB  - BACKGROUND: In the UK, travel health advice is mainly provided by practice nurses
      and general practitioners (GPs). The need for their improved education in travel
      medicine has been highlighted through previous studies and by an increasing
      number of requests for training. METHODS: A questionnaire-based survey of 3900 GP
      practices was conducted to assess training requirements and to establish the
      demand for an academic course in travel medicine. 1430 (37%) questionnaires were
      completed. RESULTS: 93% of practices provided a pretravel advice service. 87% of
      GPs advised an average of 10 travelers per month and only 48% immunized
      travelers. 98% of nurses advised and immunized an average of 28 travelers a
      month. 21% of GPs and two-thirds of nurses had attended one or more training
      sessions in travel medicine. Over 90% of the sample (83% of GPs and 98% of
      nurses) expressed an interest in attending a formal training program in travel
      medicine. Eligibility for Post Graduate Education Awards (PGEA) was important for
      most GPs (88%). Nurses valued approval by the English National Board for Nursing
      (88%) and a system of Credit Accumulation & Transfer (CATS) (82%). Funding for a
      course would be met in full by 18% of respondents (mainly GPs) and a further 20%
      would contribute to fees. Most GPs and nurses have ready access to a range of
      information sources, e.g., a postgraduate medical centre (85%) and a medical
      library (91%). Computerized access to information was feasible as 93% had a
      computer and 54% had a modem attached. CONCLUSIONS: The discipline of travel
      medicine is becoming increasingly specialized. Future practitioners will need to
      enhance their skills to meet the demands of today's travelers. Our results show
      that general practice staff are keen to develop such skills. Specialist training
      courses need to be expanded to meet this demand.

PMID- 9772309
TI  - Impact of melatonin on driving performance.
AB  - BACKGROUND: Because millions of people are self-prescribing melatonin for various
      indications, the safety aspects of this substance have become very important. The
      aim of our study was to determine whether or not melatonin impairs driving
      related performance. METHODS: Twenty healthy men and women aged 21-57 years
      volunteered for this randomized, placebo-controlled, double-blind, crossover
      study. The crossover arms were separated by an interval of at least 4 weeks. On
      each testing day, melatonin 5 mg or placebo was taken at 1630 h; 60 minutes later
      a test series was performed, consisting of a medical examination, body sway
      measurement, and a standardized driving computer test battery to assess
      attention, reaction time, power of concentration, and sensomotor coordination.
      Subjective sleepiness was measured on three occasions during the test session
      using the Stanford Sleepiness Scale questionnaire. RESULTS: Just one of the 16
      main variables of the driving computer test battery, the selective attention
      tested by signal-detection, was significantly affected by melatonin (p < .05).
      However, even those values were still within the normal range. Subjective
      sleepiness was increased by melatonin, although the result was significant only
      after the prolonged concentration task (p < .05). Neither the clinical
      examination nor the body sway test showed signs of any drug influence.
      CONCLUSIONS: The overall result of the computer test battery showed no objective
      adverse impact of melatonin on driving performance. However, due to the increased
      subjective sleepiness after administration of this hormone, caution should be
      exercised when driving under the influence of melatonin.

PMID- 9772310
TI  - Patient compliance in the use of Vivotif Berna(R) vaccine, typhoid vaccine, live
      oral Ty21a.
AB  - BACKGROUND: Several live attenuated vaccines against bacterial enteric pathogens
      have recently been licensed. These include the Salmonella typhi Ty21a typhoid
      vaccine (Vivotif Berna(R) Vaccine) and Vibrio cholerae CVD103-HgR cholera vaccine
      (Mutacol Berna(R) Vaccine). They comprise a unique class of biologics in which
      patient compliance is required for their optimal use. This is of particular
      importance in the case of the Ty21a vaccine strain of which multiple doses are
      required. Furthermore, exposure to heat, concomitant use with antibiotics or
      antimalarial drugs, and timing of vaccination with respect to food intake can
      affect vaccine potency and/or efficacy. This study was conducted to determine the
      level of compliance among adult North American travelers and to evaluate
      compliance errors with respect to potential vaccine efficacy. METHOD:
      Questionnaires were provided to 1091 travelers at twelve travel clinics in the
      United States and Canada. The patients were requested to complete forms which
      asked questions relating to vaccine storage and usage, and to return them to the
      travel clinic. A total of 762 completed questionnaires were returned. RESULTS:
      Few compliance errors were made regarding proper storage of the vaccine. The most
      common compliance errors involved not taking all four capsules on alternate days
      (10%) and not taking all four doses of vaccine prior to departure (6%).
      CONCLUSIONS: Pretravel counselling was effective in obtaining a high compliance
      rate among adult travelers in the use of Vivotif Berna(R) Vaccine. The majority
      of compliance errors reported would not be expected to negatively impact upon
      vaccine efficacy.

PMID- 9772311
TI  - Immunogenicity and reactogenicity of Avaxim (160 AU) as compared with Havrix
      (1440 EL.U) as a booster following primary immunization with Havrix (1440 EL.U)
      against hepatitis A.
AB  - BACKGROUND: Hepatitis A vaccination is recommended for travelers from the UK to
      areas of moderate or high endemicity. Two licensed hepatitis A vaccines are now
      available in the UK, and this trial was undertaken to determine whether Avaxim
      can be used as a booster following a primary course of Havrix. METHODS: One
      hundred and eighty-five subjects were randomized to receive a booster dose of
      either Avaxim (n=92) or Havrix (n=93), 6 to 7 months after a primary dose of
      Havrix. Subjects were observed for 30 minutes for immediate reactions and
      subsequently completed a diary card for a further 2 weeks. Serology samples for
      HAV antibody titers were taken at 28 6 7 days later. RESULTS: One month following
      the booster dose, all subjects in both treatment groups achieved HAV antibody
      titers >= 20 mIU/mL. In the Avaxim group, geometric mean titer (GMT) values
      increased from 642 mIU/mL (97.5% CI 330-1250 mIU/mL) to 6669 mIU/mL (4566-9740
      miu/mL), compared with 739 mIU/mL (379-1443 mIU/mL) at baseline to 4460 mIU/mL
      (2880-6908 mIU/mL) following the administration of Havrix. The increase in GMT
      following the administration of Avaxim was significantly greater than that
      following Havrix (p=.02). Eight percent of subjects reported pain at the
      injection site following a booster dose of Havrix, compared with none following
      Avaxim. This difference in reactogenicity was statistically significant (p=.01).
      In all other respects, both preparations were safe and equally well tolerated.
      CONCLUSION: Either Avaxim or Havrix may be given as a booster dose of hepatitis A
      vaccine when Havrix has been administered as the primary dose.

PMID- 9772312
TI  - Campylobacter jejuni as a cause of traveler's diarrhea: clinical features and
      antimicrobial susceptibility.
AB  - Traveler's diarrhea is the most common health problem of international travelers.
      Although enterotoxigenic Escherichia coli seems to be the most frequent cause of
      traveler's diarrhea, many other microorganisms, such as Campylobacter jejuni, may
      cause this infectious disease. Campylobacter jejuni is recognized as a leading
      cause of enteritis in humans both in developing and in developed countries.
      However, a few reports on the incidence and antimicrobial resistance of
      Campylobacter spp. as a cause of traveler's diarrhea have been published. The
      limited data on the treatment of C. jejuni infections suggest that ciprofloxacin
      may shorten the duration of symptoms. However, treatment failure associated with
      the emergence of quinolone-resistant strains of C. jejuni has been documented.
      The purpose of this study was to determine the prevalence of C. jejuni associated
      with traveler's diarrhea and to analyze the geographic distribution as well as
      the clinical features and susceptibility to antibiotics.

PMID- 9772313
TI  - Problems with rabies postexposure management: a survey of 499 public hospitals in
      Thailand.
AB  - Rabies is still a major public health problem in Asia. The incidence of known
      annual human cases in India alone has recently been revised from 20,000 to
      30,000, and over 500,000 patients are given some form of postexposure rabies
      treatment. Only China, Peninsular Malaysia, Singapore, and Thailand are reporting
      a significant decrease in the prevalence of this disease in humans. Over 150,000
      courses of postexposure treatment (PET) are given in Thailand every year. To
      determine remaining barriers to further reduction of the number of human rabies
      deaths, we carried out a questionnaire study of government hospitals throughout
      the Kingdom.

PMID- 9772314
TI  - Epidemiology and eradication of Schistosomiasis japonica in Japan.
AB  - Schistosomiasis japonica caused by Schistosoma japonicum, owes its name to the
      historical work of Japanese scientists during the period of 1904 to 1913. The
      disease is currently endemic in China and in the Philippines. It was highly
      endemic in three regions of Japan, but has been declared eradicated as of 1996.
      This paper presents epidemiologic data about when the disease was actively
      transmitted in Japan and how the disease was eradicated, and reviews evidence
      that fresh water even in the most heavily snail-infested areas is now safe from
      the disease. Information on epidemiology was obtained from Nation's Health
      published by the Japan Public Health Society. Similar information on numbers of
      fatal cases was obtained from the annual publication Morbidity and Mortality
      Record of the Ministry of Health of Japan.

PMID- 9772315
TI  - Use of malarial prophylaxis amongst a population of expatriate church workers in
      Northeast Zaire.
AB  - In common with much of subSaharan Africa, falciparum malaria is a major cause of
      mortality and morbidity amongst the indigenous population of northeast Zaire1
      although there are some mountainous areas in the east of the region that are
      relatively free from the parasite. There are a significant number of expatriate
      church workers (missionaries) in the area who work mainly in the health and
      development sector or directly with the local church in bible translation,
      evangelism, etc. The lifestyle of these workers, who tend to live close to the
      indigenous population, and their length of stay in a malarious region means that
      they are at high risk of contracting malaria.1 This population has been
      inadequately studied concerning its use of chemoprophylaxis and other measures
      necessary to reduce the risk of malaria. Many countries have published
      guidelines2-4 on the use of chemoprophylaxis for the prevention of malaria in
      travelers. This study was planned to investigate whether these guidelines were
      being followed by this group of missionaries. It also enabled the author to
      investigate who or what influences decisions regarding malaria prophylaxis
      amongst this population.

PMID- 9772316
TI  - Severe and complicated Falciparum malaria in Italian travelers.
AB  - Imported malaria has been an important public health problem in Western countries
      in the last 20 years, since international travel has become an increasing habit
      for nonimmune populations and since chemoresistance to most antimalarial drugs
      has been spreading throughout the world. Moreover, immigration from African and
      Asian countries has been rapidly increasing, especially in Italy in the last few
      years. Malaria had been widespread in Italy in the past, but no new autochthonous
      cases have been reported since 1961. Nonetheless the number of reported cases
      throughout the country has been steadily growing because of imported malaria1-3
      in nonimmune travelers as well as in immigrants from tropical countries. In our
      experience as well as according to other statistics, the vast majority of
      patients have Plasmodium falciparum malaria acquired in Africa.4,5 The clinical
      spectrum of this disease is wide, and severe cases are frequently observed,
      including a few fatal cases, which, although rare, are highlighted by mass media
      and impress the public opinion.5-8 The purpose of this study was to examine the
      clinical spectrum of malaria, with particular interest in severe falciparum
      malaria, and to define the frequency of this phenomenon and epidemiologic
      characteristics of patients who experience it as a life-threatening disease.

PMID- 9772317
TI  - Evidence of dengue virus infection in a german couple returning from hawaii 
AB  - Dengue is an acute, mosquito-transmitted viral disease characterized by fever,
      arthralgia, myalgia, rash, nausea, and vomiting and caused by any of four
      different serotypes of the virus (DEN-1, DEN-2, DEN-3, and DEN-4).1 The disease
      is endemic in most tropical areas of the world and has been reported in
      international travelers returning from such areas.2 The incidence of epidemic and
      endemic dengue has increased substantially in the Americas since 1977, and
      various epidemics have occurred.1-4

PMID- 9772318
TI  - Sexually active adolescents and young adults: a high-risk group for Chlamydia
      trachomatis infection.
AB  - BACKGROUND: The importance of travel as a risk factor for Chlamydia trachomatis
      infection was evaluated among a series of young people consecutively tested.
      METHODS: We studied 130 sexually active young subjects, aged 14-25 years, all
      living in the Rome, Italy, urban area. Ninety-eight females and 32 males attended
      hospital-based clinics or were the partners of an infected female. About half of
      these subjects had traveled abroad either for pleasure or for work, mostly to
      Europe, but also to North America or to Asia, where they admitted to having had
      casual sex. We used two "gold standard" methods to diagnose infection with C.
      trachomatis: culture on McCoy cells grown in shell vial, and direct
      immunofluorescence with monoclonal antibodies. Subjects were considered infected
      when at least one test was positive. RESULTS: Thirty-nine of 130 (30%) subjects
      were asymptomatic, and 27/130 (20.8%) subjects were infected with Chlamydia
      trachomatis, of whom 6/25 (24%) asymptomatic females and 3/14 (21.4%)
      asymptomatic males were infected. Among teen-aged (ages 14-19) youngsters with
      more than one sex partner, international travel was an additional significant
      risk factor for C. trachomatis infection (p<.02; OR 20; 95% CI 1.47-40%).
      Urethritis/cystitis and vaginal pathology/discharge were the prevalent
      manifestations of illness among the females, while urethritis was the only
      clinical condition found in the males. CONCLUSION: In a series of young subjects,
      travel abroad, sex with more than one partner, and teen age, combined together,
      were significant risk factors for the acquisition of Chlamydia trachomatis
      genitourinary infection.

PMID- 9772319
TI  - Safety advice for travelers from New Zealand.
AB  - BACKGROUND: Accidents and injuries are important preventable causes of morbidity
      and mortality for travelers. This study was designed to investigate the
      prevalence of advice given by general practitioners (GPs) on personal safety,
      health and travel insurance, and finding medical assistance abroad in the event
      of misadventure or ill health. METHOD: Four hundred general practitioners were
      randomly selected from the register of the New Zealand Medical Council and sent
      self-administered questionnaires. Two reminders were sent. RESULTS: Three hundred
      and thirty-two (83%) GPs responded. Advice to travelers on health and travel
      insurance (164/273, 60%), personal safety (127/255, 50%), and finding medical
      assistance abroad (165/308, 54%) was given by half or just over half of GPs.
      Giving advice on medical assistance abroad was significantly associated with
      giving advice on health and travel insurance (x2 = 18.89, df = 1, p<.001) and
      personal safety (x2 = 25.26, df = 1, p<.001). Seeing a higher proportion of
      patients who were travelers was significantly associated with giving advice on
      health and travel insurance (t-value = -3.39, df = 267, p = .001) and personal
      safety abroad (t-value = -2.63, df = 249, p < .01). Those GPs with previous
      experience in tropical medicine/developing countries were significantly more
      likely to advise travelers on personal safety abroad (x2 = 6.55, df = 1, p<.05)
      and about seeking medical assistance abroad (x2 = 4.11, df = 1, p<.05). Those GPs
      in older age groups (45-49 years and over) were significantly more likely to
      advise travelers on health and travel insurance (x2 = 16. 31, df = 8, p<.05) and
      personal safety abroad (x2 = 19.88, df = 8, p<.05). Those GPs with an interest in
      travel medicine were significantly more likely to advise travelers about seeking
      medical assistance abroad (x2 = 11.07, df = 1, p<.001) and health and travel
      insurance (x2 = 16.31, df = 8, p<.05). When advising travelers about seeking
      medical assistance abroad, GPs most commonly recommended contacting travel
      insurance companies (60/308, 19%), a specific medical service (48/308, 16%), tour
      company (30/308, 10%), specific doctor (29/308, 9%), New Zealand embassy (27/308,
      9%), local medical service (23/307, 7%), personal contact (21/307, 7%), and other
      sources (12/307, 4%). CONCLUSIONS: This cross-sectional study found that only
      around half of New Zealand GPs were giving advice to travelers on personal
      safety, health and travel insurance, and finding medical assistance abroad.
      Continuing education providers should reinforce the need for this advice to be
      given to all travelers. There was also considerable variability in what New
      Zealand GPs recommended to travelers about seeking medical assistance abroad,
      including several nonmedical sources.

PMID- 9772320
TI  - Diarrhea in returning Austrian tourists: epidemiology, etiology, and cost
      analyses.
AB  - BACKGROUND: Between 1995 and 1997, stool samples of 322 Austrian tourists
      returning from abroad with diarrhea were examined for bacteria, parasites and
      viruses. METHODS: Epidemiologic data were collected from information furnished by
      physicians and hospitals and from questionnaires. Moreover, testing expenses and
      additional cost for treated cases were evaluated. RESULTS: In 97 of 322 patients
      examined (30%), one or more pathogens were detected in the stool. Bacteria were
      found in 38 patients (39%), parasites in 33 patients (34%) and viruses in 26
      patients (27%). In 6 patients, mixed infections with parasites and viruses were
      detected and in 5 patients with bacteria and viruses. Among bacteria,
      Campylobacter jejuni was most frequent; among parasitic infections, Giardia
      lamblia. Significant correlations were established between the country of
      destination, age, travel style and length of stay. Forty-four percent of all
      patients visited Asia (including Turkey), 27% Africa, 18% Latin America, and only
      10% southern Europe. The group between 20 and 29 years of age was most frequently
      affected (p<.001), the group between 0 and 19 years of age least. Fifty-seven
      percent stayed in a hotel without frequent changes of location; 43% undertook a
      trekking trip; and of those, 75% belonged to the group aged between 20 and 39. In
      terms of the correlation between travel style and pathogen, it was found that 74%
      of patients with bacterial infections stayed in a hotel (avg. 57.9%; p<.05)
      whereas 64% of all patients with parasitic infections undertook a trekking trip
      (avg. 42%; p<.001). Thirty-six percent of all patients with parasitic infections
      spent their vacation in India (avg. 13%; p<.001). The length of stay of patients
      with bacterial infections was shorter than average (72% spent between 1 and 2
      weeks abroad, avg. 49.8%). Patients with parasitic infections spent significantly
      more time abroad than average (42% more than 2 months; avg. 17.7%; p<.001).
      Average cost of specific antimicrobial therapy was U.S.$31 whereas the average
      cost of identifying a patient needing such treatment was almost U.S.$580.
      CONCLUSION: Optimal detection rate and cost reduction for the diagnosis require
      precise history, adequate collection of samples using adequate transport media,
      and rapid transfer to the laboratory.

PMID- 9772321
TI  - Sources and appropriateness of medical advice for trekkers.
AB  - BACKGROUND: Little has previously been published on the sources of health advice
      used by trekkers. This paper investigates the sources of advice used by a group
      of British trekkers and the appropriateness of the advice which they were given.
      METHODS: A questionnaire was issued to 107 clients of a U.K. trekking operator.
      Clients were asked which advice sources they had used and how useful they found
      them. They were also asked about advice which they had received on vaccination,
      antimalarial drugs, and other health precautions. The appropriateness of such
      advice was assessed by reference to standard advice sources used in the United
      Kingdom. RESULTS: One hundred replies were received, a response rate of 93.5%.
      Responders had traveled to India (10%), Nepal (45%) and Morocco (45%). The most
      frequently used advice sources were general medical practitioners or health
      centers (69%) and the tour operator (68%), many trekkers using more than one
      source. Specialist travel advice centers and general practitioners were rated
      most highly by 67% and 59% of users for usefulness and 60% and 52% of users for
      being informative. Other travelers were also rated highly as a source. Some
      appropriate vaccinations were under-recommended while others which were not
      appropriate were recommended. Antimalarial drugs were recommended when needed but
      they were sometimes recommended when not appropriate. Advice on other health
      risks was generally inadequate. CONCLUSIONS: Trekkers need access to more
      relevant health advice. Tour operators need to have better medical information to
      pass on to their clients, and health professionals need more education about
      health risks for and the avoidance of health risks by trekkers.

PMID- 9772322
TI  - Culture shock and travelers.
AB  - As travel has become easier and more affordable, the number of people traveling
      has risen sharply. People travel for many and varied reasons, from the business
      person on an overseas assignment to backpackers seeking new and exotic
      destinations. Others may take up residence in different regions, states or
      countries for family, business or political reasons. Other people are fleeing
      religious or political persecution. Wherever they go and for whatever reason they
      go, people take their culture with them. Culture, like language, is acquired
      innately in early childhood and is then reinforced through formal and complex
      informal social education into adulthood. Culture provides a framework for
      interpersonal and social interactions. Therefore, the contact with a new culture
      is often not the exciting or pleasurable experience anticipated. When immersed in
      a different culture, people no longer know how to act when faced with disparate
      value systems. Contact with the unfamiliar culture can lead to anxiety, stress,
      mental illness and, in extreme cases, physical illness and suicide. "Culture
      shock" is a term coined by the anthropologist Oberg. It is the shock of the new.
      It implies that the experience of the new culture is an unpleasant surprise or
      shock, partly because it is unexpected and partly because it can lead to a
      negative evaluation of one's own culture. It is also known as cross-cultural
      adjustment, being that period of anxiety and confusion experienced when entering
      a new culture. It affects people intellectually, emotionally, behaviorally and
      physically and is characterized by symptoms of psychological distress. Culture
      shock affects both adults and children. In travelers or workers who have
      prolonged sojourns in foreign countries, culture shock may occur not only as they
      enter the new culture, but also may occur on their return to their original
      culture. Children may also experience readjustment problems after returning from
      leading sheltered lives in expatriate compounds. This readjustment back to their
      own culture after a period of time abroad has been termed "reverse culture shock,
      a condition which has been studied in both corporate managers and Peace Corps
      volunteers. With culture shock and many other processes of psychological
      adjustment, people tend to suffer alone, thinking that they are the only ones not
      coping well with their new circumstance. The objective of this paper was to bring
      the phenomenon of culture shock to the awareness of travel health advisors, who
      can in turn advise travelers, especially longer term travelers, about having
      realistic expectations of their travel and life in new cultures.

PMID- 9772323
TI  - Chemoprophylaxis compliance in travelers with malaria.
AB  - Much effort and resources have been focused on improving or evolving antimalarial
      prophylactic regimens in order to reduce the increasing problems of malaria
      infection in nonimmune travelers to malaria endemic regions. Falciparum malaria
      in travelers returned from Africa has been attributed to reduced efficacy of
      chloroquine against chloroquine-resistant strains of Plasmodium falciparum
      (CRPF). Reported prophylaxis use by tourists from East Africa suggests only 52%
      admit taking their chemoprophylaxis without any missed doses. The effect of
      noncompliance with chloroquine (CQ) or proguanil (PG) in East Africa has been
      estimated as equivalent to taking no prophylaxis at all. The influence of poor
      compliance and/or parasite resistance on the changing pattern of malaria among
      travelers needs to be understood if methods of reducing morbidity are to be
      identified. In a number of studies, prophylaxis compliance in travelers has been
      collected by self-administered questionnaires from which prophylaxis efficacy of
      drug regimens has been calculated. The interpretation of drug efficacy has hinged
      on drug compliance and is controversial. We have addressed the role of
      chemoprophylaxis compliance in travelers with malaria using a prospective study
      of 368 malaria patients attending the Hospital for Tropical Diseases by examining
      their travel history and reported prophylaxis compliance compared to their actual
      plasma drug levels. This has enabled us to characterize the role of CRPF and poor
      compliance in the etiology of breakthrough malaria in travelers.

PMID- 9772325
TI  - Imported severe falciparum malaria in Israel.
AB  - Malaria remains an overwhelming problem in tropical developing countries, with
      300 to 500 million new cases and 1.5 to 3.5 million deaths per year. Malaria is a
      potentially life-threatening disease for travelers to the tropics. Imported
      malaria is an important clinical problem in nonendemic areas of the world because
      of increasing numbers of travelers, overseas workers, and immigrants from endemic
      areas. According to the World Health Organization's criteria, the recognition of
      one or more of the following clinical features should raise the suspicion of
      severe malaria: cerebral malaria (unrousable coma), severe anemia (hemoglobin <5
      g/dL), renal failure (serum creatinine >3 mg/dL), pulmonary edema or adult
      respiratory distress syndrome, hypoglycemia (glucose <40 mg/dL), circulatory
      collapse or shock, disseminated intravascular coagulation, repeated generalized
      convulsions, acidosis (pH <7.25), macroscopic hemoglobinuria, hyperparasitemia
      (>5 percent of the erythrocytes infested by parasites), or jaundice (bilirubin >3
      mg/dL). Although only a small proportion of patients with malaria develops severe
      manifestations, these patients require the most urgent and intensive care.
      Mortality among patients with cerebral malaria, even when treated in modern
      intensive care units, exceeds 30%, and when complicated by the adult respiratory
      distress syndrome, it may approach 80%. Among travelers, mortality remains a
      serious issue because of failure to obtain and use preventive measures, delay in
      seeking medical attention, and misdiagnosis.

PMID- 9772324
TI  - Simultaneous amoebic liver abscess and hepatitis A infection.
AB  - Hepatitis A virus (HAV) infection and amoebic liver abscess have an identical
      mode of transmission (fecal-oral route) and similar epidemiology. Either of these
      diseases might be considered in patients presenting with clinical signs and
      symptoms of liver disease in areas of the world where hepatitis and Entamoeba
      histolytica are endemic. The following two cases describe patients with
      simultaneous infection of HAV and amoebic liver abscess. This report emphasizes
      the role of dual infection in patients from endemic areas. It also challenges the
      assumption that jaundice in patients with amoebic liver abscess is due to amoebic
      hepatitis, rather than co-infection with viral hepatitis.

PMID- 9772326
TI  - Doxycycline as first line malarial prophylaxis: how safe is it?

PMID- 9772327
TI  - In pursuit of the persistent plasmodium.

PMID- 9772328
TI  - Concomitant vaccination against hepatitis A and typhoid fever.
AB  - BACKGROUND: The purpose of this study was to evaluate the reactogenicity and
      immunogenicity of a hepatitis A vaccine (Havrix-1440TM) when administered
      simultaneously with a Vi polysaccharide typhoid vaccine. METHODS: Two open,
      randomized studies were conducted using 2 and 4 treatment groups respectively, at
      the Clinique Notre-Dame de Grace, Belgium (Study 1) and University Hospital of
      Hradec Kralove, Czech Republic (Study 2). SUBJECTS: Healthy adults aged 18-50
      years were administered either both vaccines concomitantly in separate arms or a
      single injection of the two vaccines mixed extemporaneously (Study 1), or one
      injection of each vaccine alone, or the combined vaccine, or both vaccines
      concomitantly in separate arms (Study 2). The study measured solicited and
      unsolicited signs and symptoms until 28 days post-vaccination. Anti-hepatitis A
      and anti-Vi titers were determined in pre- and post-vaccination sera. RESULTS:
      The vast majority of local and general symptoms were mild to moderate and all
      resolved without sequelae. No serious adverse events were reported in either
      study. In study 1, geometric mean antibody titers (GMTs) were similar after
      extemporaneous syringe mixing of both vaccines (anti-Vi = 1159 EL.U/mL; anti-HAV
      = 302 EL.U/mL) and after concomitant vaccination (anti-Vi = 1331 EL.U/mL; anti
      HAV = 367 EL. U/mL). In study 2, GMTs following vaccination with either vaccine
      alone, both vaccines administered concomitantly or as a combined vaccine (anti
      Vi: 1307, 1247 and 942 EL.U/mL, respectively; anti-HAV: 462, 517 and 432 EL.U/mL,
      respectively) were not significantly different (p = .45 for anti-HAV, p = .18 for
      anti-Vi). Seroconversion rates were > 94.4% in all cases. CONCLUSIONS: The
      inactivated hepatitis A and Vi polysaccharide typhoid vaccines are safe and well
      tolerated when administered simultaneously (mixed or concomitant) and as a
      combined vaccine. Subjects seroconverted to both antigens to the same extent as
      the monovalent vaccines and there was no cross-interference in the immune
      profiles of the vaccines.

PMID- 9772329
TI  - Safety of mefloquine and other antimalarial agents in the first trimester of
      pregnancy.
AB  - BACKGROUND: Safe and effective antimalarials are required to protect pregnant
      women from the harmful effects of malaria. METHODS: Data were collected from two
      separate prospective cohorts to ascertain the safety of chloroquine-proguanil,
      sulfadoxine-pyrimethamine (SP), and mefloquine taken in the first trimester of
      pregnancy. RESULTS: In a traveler cohort of 236 pregnant women, spontaneous
      abortions were reported in 7.6% of 99 women taking chloroquine-proquanil, 0% of
      19 taking sulfadoxine-pyrimethamine, and 9.1% of 118 women taking mefloquine.
      Anomalies were identified in 1.7%, 0% and 0% of the same cohort, respectively.
      Differences in rates of adverse outcomes between the three groups were not
      statistically significant. In a pharmaceutical database of 331 and 153 women
      exposed to mefloquine and SP, respectively, the overall rate of abnormal outcomes
      (spontaneous abortions plus fetal anomalies) was not significantly different
      (p=.29). Spontaneous abortions were significantly higher with mefloquine than SP
      (9.1% and 2.6%, respectively; p=.01), but the higher rate was comparable to
      background rates (7%-11%). Fetal anomalies in the mefloquine group (4.8%) were
      lower than the SP group (7.8%), but this was statistically not significant
      (p=.19), and was comparable with the background rate of 4.6% (p=.84). However,
      mefloquine exposure resulted in a significantly higher rate of therapeutically
      induced abortions, undertaken for perceived risk to the fetus, compared with SP
      (p<.0001). CONCLUSION: From the clinical data available, there is no indication
      that the risk of taking mefloquine in the first trimester of pregnancy is greater
      than that from any of the other antimalarials studied and the risk is
      considerably lower than that associated with falciparum malaria.

PMID- 9772330
TI  - Epidemiology of giardiasis in Tasmania: a potential risk to residents and
      visitors.
AB  - BACKGROUND: Giardia infection is an ongoing problem in Tasmania and occurs
      throughout the state. It has been postulated that part of the problem is the
      reservoir of infection in native animals which is suggested to contribute to
      infections in humans. To date, however, no detailed study on the epidemiology of
      giardiasis in Tasmania has been carried out. METHODS: Information regarding the
      prevalence of Giardia infection in humans and the risk of intrafamilial
      transmission was obtained from the Department of Community and Health Services
      and from the direct examination of human or animal fecal samples. RESULTS:
      Giardia has been found to be present in a wide range of native and domestic
      animals and in humans of all ages from all over the state. CONCLUSIONS:
      Giardiasis is endemic in Tasmania and poses a risk to locals as well as to
      visitors to the state, especially those who participate in wilderness activities
      such as bushwalking. These people must be aware of the possible risk of Giardia
      infection and should take precautionary measures to avoid infection.

PMID- 9772331
TI  - Cutaneous tuberculosis: a rare presentation in an immigrant.
AB  - The increased incidence of tubercular diseases in industrialized countries
      appears to be due to several factors, including development of resistance to the
      most commonly used specific chemotherapeutic substances, unsuitable control
      programmes, HIV infection, the increased influx of immigrants, and homelessness.
      Different forms of cutaneous tuberculosis are caused by different species of
      mycobacteria (e.g., Mycobacterium tuberculosis, M. bovis, M. avium). Determining
      the species of mycobacteria is relevant when disease is suspected to be linked to
      the type of employment of the patient, mainly because the clinical features do
      not always indicate which species is the cause of the infection. Mycobacterium
      tuberculosis (MT) usually infects through the lung, but in rare cases can
      penetrate the skin or mucous membranes. Skin transmission can be exogenous by
      inoculation, or endogenous by diffusion (lymphatic or hematic) or by contiguity.
      The immunologic status of the patient is a crucial factor which influences the
      clinical variants and the course of disease itself. Here we report a case of an
      illegal immigrant who presented with a bilateral, symmetrical ulcer on the neck.

PMID- 9772332
TI  - Dangers in the ocean: the traveler and marine envenomation. I. jellyfish.
AB  - Envenomation by marine creatures is more common than is often realized, and
      regularly accounts for both death and severe morbidity in humans. Worldwide
      marine envenomation morbidity and mortality result from two main animal groups:
      (1) jellyfish, and (2) "other" marine animals. Venomous jellyfish are discussed
      in part I of this article, with relevant information on their distribution and
      appearance, and on symptoms of envenomation; first aid and medical treatment are
      also suggested.

PMID- 9772333
TI  - Schistosomiasis presenting as acute appendicitis in a traveler.
AB  - Schistosomiasis, a waterborne trematode infestation, is one of the most
      widespread parasitic diseases in the world. It occurs in well-defined endemic
      geographical areas. Schistosomiasis of the appendix was first described by Turner
      in 1909, and has been reported from endemic areas. However, appendicular
      schistosomiasis in travelers has not been reported in the English literature. We
      describe an Israeli traveler with acute appendicitis as the presenting symptom of
      schistosomiasis, 2 years after a visit to Africa.

PMID- 9772336
TI  - Annual physiology symposium1997. tainan, taiwan, october 17-19, 1997 

PMID- 9772334
TI  - Cyclosporiasis in a traveler returning from South America.
AB  - Cyclospora is a coccidian, previously referred to as a cyanobacterium-like body,
      with an epidemiology similar to that of Cryptosporidium parvum. In recent years,
      several studies have shown that Cyclospora is not a rare opportunistic pathogen
      but rather is the cause of common, worldwide intestinal infections in healthy
      adults and children. Previous reports of diarrhea resulting from Cyclospora sp.
      have been linked to travelers and immunocompromised patients. The species has a
      worldwide distribution. Although Cyclospora infection has been reported from
      Southeast Asia, Papua New Guinea, Indonesia, India, Pakistan, Nepal, the Middle
      East, North Africa, the United Kingdom, the Caribbean, the United States, Central
      America, and South America, the true prevalence of this parasite in any
      population is unknown. The parasite is associated with prolonged self-limiting
      and relapsing watery diarrhea, anorexia, fatigue, and sometimes myalgia. Fever is
      infrequent.

PMID- 9772338
TI  - Large somal size is associated with the expression of galanin but not with
      neuronal birthdate in the sexually dimorphic male nucleus of ferret's preoptic
      area/anterior hypothalamus.
AB  - Using Nissl and Golgi stains, a sexually dimorphic male nucleus (MN) comprised of
      a cluster of large cells with large dendritic arbors has been identified in the
      dorsal preoptic area/anterior hypothalamus (POA/AH) of male ferrets. The MN
      POA/AH is formed only in males by the action of estradiol derived from the neural
      aromatization of testosterone during the last quarter of a 41-day gestation. The
      ferret's dorsal POA/AH is also characterized by a sex difference in the
      expression of the neuropeptide galanin which first arises in males around
      embryonic day (e) 34. We asked whether the male-typical phenotype of large somal
      size is related to birthdate and/or the capacity of dorsal POA/AH neurons to
      express galanin. In experiment 1 we labeled cohorts of cells born on E20, E24, or
      E28 by injecting the amniotic sacs of individual fetuses with the thymidine
      analogue bromodeoxyuridine (BrdU). On postnatal day 20, BrdU-immunoreactive cells
      were visualized immunohistochemically, counterstained with cresyl violet, and
      their somal sizes were measured. BrdU-immunoreactive cells were significantly
      larger in the males' MN-POA/AH than in a comparable region of females, regardless
      of when they were born between E20 and E28. In experiment 2 galanin
      immunoreactive cells in the dorsal POA/AH of adult ferrets were visualized
      immunohistochemically, and their somal sizes were measured. Somal areas of
      galanin-immunoreactive cells were significantly larger in the MN-POA/AH of
      intact, breeding, or castrated and testosterone-treated males than in the
      corresponding area of females. Our results suggest that cells in the males' MN
      POA/AH are more likely to be larger than cells in females' corresponding region,
      regardless of birthdate. Finally, in adulthood the male-typical phenotype of
      large Nissl-stained somal areas of MN-POA/AH cells may, in part, reflect their
      increased galanin expression.

PMID- 9772339
TI  - Neuronal labeling in the rat brain and spinal cord from the ovary using viral
      transneuronal tracing technique.
AB  - In the present investigations the viral transneuronal labeling method, which is
      able to reveal hierarchial chains of central nervous system (CNS) neurons, was
      applied to identify sites in the CNS connected with the ovary and presumably
      involved in the control of ovarian functions. Pseudorabies virus was injected
      into the ovaries of rats and a few days later (at various times after the
      injection) the spinal cord and brain were examined for virus-infected neurons
      from the ovary. The virus-labeled nerve cells were identified by
      immunocytochemistry using polyclonal antiviral antibody. Virus-labeled neurons
      were detected both in the spinal cord and the brain. In the spinal cord such
      elements were observed in the intermediolateral cell column, in the dorsal horn
      close to the marginal zone and in the central autonomic nucleus. In the medulla
      oblongata and pons, neurons of several nuclei and cell groups (area postrema,
      nucleus of the solitary tract, dorsal vagal complex, nucleus ambiguus,
      paragigantocellular nucleus, parapyramidal nucleus, A1, A5 and A7 cell groups,
      caudal raphe nuclei, locus ceruleus, subceruleus nucleus, Barrington's nucleus,
      Kolliker-Fuse nucleus) were found to be transneuronally labeled. In the
      mesencephalon, the ventrolateral part of the periaqueductal gray matter contained
      virus-labeled neurons. In the diencephalon, a very intensive cell body labeling
      was observed in the hypothalamic paraventricular nucleus and a few virus-infected
      neurons could be detected in the lateral and dorsal hypothalamus, in the arcuate
      nucleus, zona incerta, perifornical area and in the anterior hypothalamus.
      Concerning the telencephalic structures, virus-labeled cells were found in the
      bed nucleus of the stria terminalis and in the central amygdala nucleus. These
      findings provide the first neuromorphological evidence for the existence of a
      multisynaptic neuronal pathway between the ovary and the CNS, and give a detailed
      account of the structures involved in this pathway.

PMID- 9772337
TI  - Developmental sex differences in estrogen receptor-beta mRNA expression in the
      mouse hypothalamus/preoptic region.
AB  - Estrogens play a significant role during mammalian brain development and are
      required for the masculinization of neuronal circuits involved in sex-specific
      behaviors and neuroendocrine functions. Cellular estrogen signalling is
      transmitted through nuclear estrogen receptors (ER) which are divided into two
      subforms: the ER-alpha as well as the recently cloned ER-beta have been
      demonstrated in the hypothalamus. In the present study, we have analyzed the sex
      specific expression of ER-beta mRNA in the pre- and postnatal mouse
      hypothalamus/preoptic region (Hyp/POA) by semiquantitative RT-PCR. The ER-beta
      mRNA was detectable as early as embryonic day (E) 15 in the diencephalon of both
      sexes. In males, levels of mRNA expression in the Hyp/POA increased until birth
      and remained high throughout postnatal (P) development, whereas in females, such
      an increase was not observed. Significantly higher mRNA levels were detected in
      the male Hyp/POA from E17 until P15. Perinatal sex differences in ER-beta mRNA
      expression coincide with higher estrogen-forming rates in the male Hyp/POA. At
      present, no direct evidence is available which demonstrates that estrogen
      signalling through ER-beta is involved in brain development. However, data from
      our and other studies suggest a potential role for this signal transduction
      pathway for brain differentiation.

PMID- 9772340
TI  - Diurnal rhythmicity of gonadotropin-releasing hormone gene expression in the rat.
AB  - The release of the decapeptide gonadotropin-releasing hormone (GnRH) from
      neuroterminals in the median eminence varies depending upon the stage of
      development, time of day, reproductive season, and day of the ovarian cycle. With
      respect to the biosynthetic events responsible for such alterations in GnRH
      release, we have reported that increases in GnRH mRNA occur concomitantly with or
      precede the proestrous GnRH/LH surge in female rats, and the pubertal increase in
      GnRH. Because a hallmark of puberty is the development of nocturnal increases in
      gonadotropin/GnRH release, in the present study, we examined whether a rhythm in
      GnRH gene expression occurs that may be responsible for this rhythm of
      neurosecretion. Additionally, we extended the previous finding of diurnal rhythms
      of GnRH gene expression in cycling females to adult male rats. The mechanism for
      these changes, i.e. GnRH gene transcription, RNA processing or a
      posttranscriptional mechanisms was also elucidated. In experiment I, GnRH gene
      expression was measured in female rats at different stages of puberty [P25
      (juvenile); approximately P37 (day of vaginal opening); and P45 (postpubertal)]
      at 10.00, 14.00, 18.00, 22.00, 2.00 and 6.00 h. GnRH mRNA levels increased
      significantly during pubertal development, independent of any changes in GnRH
      gene transcription or RNA processing, indicating a posttranscriptional mechanism.
      GnRH mRNA levels did not vary with time of day in these pubertal rats, indicating
      that the diurnal rhythm of GnRH release that develops during puberty is probably
      a posttranslational event. In experiment II, GnRH gene expression was measured in
      adult male rats at the same 4-hour intervals. GnRH mRNA levels varied
      significantly with time of day: they increased from 10.00 to 14.00 h, remained
      elevated through 22.00 h, then decreased significantly to the nadir at 10.00 h.
      The mechanism for these changes appears to involve processing or stability of the
      GnRH mRNA in the nucleus. These results indicate that GnRH mRNA levels are
      regulated differentially with time of day depending upon age and gender.

PMID- 9772341
TI  - Allopregnanolone-induced modification of presynaptic basal and K+-induced [3H]
      norepinephrine efflux from rat cortical slices during the estrous cycle.
AB  - Superfused frontal slices of cerebral cortex were preloaded with [3H]
      norepinephrine ([3H]NE). Basal [3H]NE efflux and K+-induced [3H]NE release were
      studied during the estrous cycle and in the presence of neurosteroids. Basal
      [3H]NE efflux showed estrous cycle-related variations, with lowest values found
      during estrus and diestrus II. Allopregnanolone (10(-9) M) potentiated basal
      [3H]NE efflux from the 1st minute of its application; the effect of the steroid
      was still present after 20 min. This effect was also dependent upon the estrous
      cycle, since basal [3H]NE efflux was mainly increased during estrus diestrus I,
      and to a lesser degree only during proestrus. During diestrus II and after
      ovariectomy, basal [3H]NE efflux was no longer affected by the neurosteroid. In
      the presence of yohimbine (10(-6) M), the effect of allopregnanolone on basal
      efflux was potentiated only during the first 3 min but vanished thereafter.
      Allopregnanolone (10(-9) M) potentiated the K+-induced [3H]NE release during
      estrus, but pregnenolone (10(-9) M) was ineffective, suggesting specificity of
      the neurosteroid. Yohimbine (10(-6) M) also potentiated K+-induced [3H]NE
      release. When applied simultaneously with allopregnanolone (10(-9) M), a
      potentiating effect on [3H]NE release was observed. The present results suggest
      that allopregnanolone is a neurosteroid able to modulate norepinephrine release
      in the cerebral cortex in an estrous cycle-dependent manner, and that the effect
      could involve noradrenergic alpha-2 receptors.

PMID- 9772342
TI  - Seizure activity is increased in endocrine states characterized by decline in
      endogenous levels of the neurosteroid 3 alpha,5 alpha-THP.
AB  - To examine the role of progesterone (P) and its 5alpha-reduced metabolite, the
      neurosteroid 5alpha-pregnan-3alpha-ol-20-one (3alpha, 5alpha-THP), in endogenous
      variations in ictal activity rats were tested for kainic acid-induced seizures in
      different hormonal milieu. Corresponding plasma and central P and 3alpha,5alpha
      THP levels were measured. Cycling Long-Evans rats in estrus and proestrus had
      seizures of significantly shorter duration and more central and plasma
      3alpha,5alpha-THP and P than animals in metestrus or diestrus. Females with
      luteal functioning had seizures of significantly shorter duration and increased
      central and plasma 3alpha,5alpha-THP and P compared to animals that recently had
      luteal functioning discontinued. Pregnant rats had significantly shorter seizures
      and greater central and plasma 3alpha,5alpha-THP and central P than animals
      tested 1-2 days postparturition. In all test paradigms, seizure activity was
      increased in animals that had decreased 3alpha, 5alpha-THP or P; overall, central
      3alpha,5alpha-THP was more inversely related to ictal activity than central P or
      plasma P and 3alpha,5alpha-THP. To investigate a causal relationship between
      3alpha,5alpha-THP and seizures, a 5alpha-reductase inhibitor, finasteride, or
      vehicle was administered to pregnant rats. Finasteride administration
      significantly decreased central and plasma 3alpha,5alpha-THP, but had no
      significant effect on plasma or central P of pregnant rats. Finasteride, but not
      vehicle administration, to pregnant rats significantly increased seizure
      duration. These findings support the hypothesis that variations in seizure
      threshold over endogenous hormonal milieu may be related to endogenous
      3alpha,5alpha-THP. Of all of the endocrine conditions, seizure durations were
      greatest in diestrus animals; this group did not experience the lowest or the
      greatest decrease in 3alpha, 5alpha-THP concentrations; however, of all of the
      endocrine conditions, cycling rats experienced the most rapid cycles of 3alpha,
      5alpha-THP variation. This suggests that cycles of endogenous variations in
      3alpha,5alpha-THP may influence seizure threshold.

PMID- 9772343
TI  - In vitro secretion of gonadotropin-releasing hormone (GnRH) and
      [hydroxyproline9]GnRH from the rat hypothalamus exhibits a differential
      sensitivity to castration and second messengers.
AB  - The decapeptide [hydroxyproline9]GnRH (HypGnRH) has been characterized as an
      endogenous posttranslational product of the gonadotropin-releasing hormone (GnRH)
      precursor in a wide range of mammalian brains. Despite consistent biological
      effects, its secretion by the hypothalamus remains hypothetical. We report here
      in vitro secretion of HypGnRH and GnRH by the hypothalamus from intact and
      castrated male rats and provide evidence that they are differentially regulated.
      Both peptides were identified by two anti-GnRH antibodies of different
      specificities after separation under two high-performance liquid chromatography
      conditions. Calcium dependency of HypGnRH release was demonstrated under
      stimulation with KCl in the absence or presence of Ca2+, as well as with Bay K
      8644, veratridine, methoxyverapamil, or tetrodotoxin. Activation of signaling
      pathways involving adenylate cyclase and protein kinases A and C (PKC) induced
      HypGnRH release. Expression of data as percentage of release over tissue stores
      revealed a two- to threefold higher release of HypGnRH than of GnRH under the
      different modes of stimulation used, except under PKC activation which triggered
      a comparable recruitment of both peptides. Castration selectively affected PKC
      coupled GnRH secretion which showed a twofold lesser release than in intact rats,
      while the HypGnRH release was unaffected. We conclude that HypGnRH and GnRH are
      not secreted from the hypothalamus according to the same mechanisms.

PMID- 9772344
TI  - Conformational changes of active site of copper zinc superoxide dismutase can be
      detected sensitively by electron-transfer reaction.
AB  - The electron-transfer (ET) reaction between Fe(CN)6(4-) and copper zinc
      superoxide dismutase (CuZn-SOD) occurs at the active site of the enzyme. The ET
      parameters which are sensitive to the denaturation have been used to determine
      the conformational changes of the active site induced by guanidine hydrochloride
      and thermal denaturation. The decreases of ET rates for all the denatured enzyme
      samples reflect the collapse of the active cavity of enzyme in the unfolding
      processes. The interesting changes of ET amplitude for the enzyme denatured at
      different pH values suggest that electrostatic interaction plays an important
      role in the conformational changes of active site. From the results of the
      kinetic analyses, it is concluded that the conformational changes of the active
      site are parallel with the inactivation.

PMID- 9772345
TI  - Variety of molecular conformation of plasmid pUC18 DNA and solenoidally
      supercoiled DNA.
AB  - The plasmid pUC18 DNA isolated from Escherichia coli HB101 were analyzed by two
      dimensional agarose gel electrophoresis and hybridization. The results show that
      the DNA sample can be separated into six groups of different structural
      components. The plectonemically and solenoidally supercoiled pUC18 DNA coexist in
      it. These two different conformations of supercoiled DNA are interchangeable with
      the circumstances (ionic strength and type, etc.). The amount of solenoidally
      supercoiled pUC18 DNA in the samples can be changed by treatment of DNA
      topoisomerases. Under an electron microscope, the solenoidal supercoiling DNA has
      a round shape with an average diameter of 45 nm. The facts suggest that
      solenoidally supercoiled DNA be a structural entity independent of histones. The
      polymorphism of DNA structure may be important to packing of DNA in vivo.

PMID- 9772346
TI  - Crystal structure determination of basic phospholipase A2 from venom of
      Agkistrodon halys pallas by molecular replacement method.
AB  - Basic phospholipase A2 (BPLA2) from the venom of Agkistrodon halys pallas has a
      strong ability to hemolyze erythrocytes. The asymmetrical unit of P2(1)2(1)2(1)
      crystal of BPLA2 contains two molecules. Self-rotation function was used to study
      the orientation relationship of these two molecules. Cross-rotation and
      translation functions were then used to determine the orientations and positions
      of the two molecules in the unit cell. The model building and preliminary
      structure refinement were carried out. The result shows that the two molecules in
      the asymmetrical unit of orthorhombic crystal are related by a non
      crystallographic 2-fold symmetry axis.

PMID- 9772347
TI  - Conformation of an analog of human follicular gonadotropin releasing peptide TF14
      in solution by 2D-NMR.
AB  - Since the discovery of hF-GRP, several analogs have been synthesized in order to
      see their effects on the gonadotropin releasing activity, either as agonists or
      antagonists to this peptide. TF14 is one of these analogs, whose 14th position in
      the primary sequence is Phe instead of Asn in hF-GRP, while its activity is
      doubled. 2D-NMR (TOCSY, ROESY) was used to determine the conformation of TF14 in
      solution. Compared with hF-GRP, the whole peptide is in a non-typical more
      extended conformation, which may give some clue to the relation between structure
      and function of these two peptides.

PMID- 9772348
TI  - Kinetics of low threshold calcium channels of relay cells in cat lateral
      geniculate nucleus.
AB  - Kinetics of the low threshold T-type Ca2+ channel is studied with single
      electrode voltage clamp technique on brain slices of the cat lateral geniculate
      nucleus (LGN). Space clamp is dramatically improved by blocking various K+ and
      Na+ channels, decreasing Ca2+ current and selecting proper holding potentials.
      Results from this study are similar to those obtained from acutely dissociated
      LGN neurons of the rat, indicating that the kinetics of T-Ca2+ channels of the
      cat LGN neurons is the same as that of the rat LGN. The result reported
      previously on the cat LGN may result from a defect in space clamp.

PMID- 9772350
TI  - Crystal structure of (L-Arg)-B0 bovine insulin at 0.21 nm resolution.
AB  - The crystal structure of (L-Arg)-B0 bovine insulin has been determined, using
      data to 0.21 nm and atomic parameters of 2Zn porcine insulin as a starting model,
      by the difference. Fourier method, the restrained least square method and X-PLOR
      package, interspersed with careful review of the electron density, to a final R
      factor of 0.182 and r.m.s. deviation of 0.002 2 nm for the bond lengths and 4.3
      degrees for the bond angles. The electron densities of additional (L-Arg)-B0
      residues to B-chain N-terminus of two monomers in each asymmetric unit are very
      clear. The crystallographic micro-environment of the N-terminus of the B-chain is
      different from that of rhombohedral 2-zinc insulin.

PMID- 9772349
TI  - The second space experiment of protein crystallization with domestic facilities.
AB  - The second experiment of protein crystallization was performed on domestic re
      entry satellite FSW-2 in 1994-07. The results are superior to the ones of the
      first mission in 1992: 9 of 10 different proteins were crystallized in space, and
      70% of the total 48 samples yielded single crystals. Besides hen egg-white
      lysozyme which grew high-quality crystals on the first mission, an acidic
      phospholipase A2(aPLA2) from snake venom and hemoglobin from Anser Indicus
      produced good-quality crystals suitable for X-ray diffraction analyses. The
      positive effect of microgravity on protein crystal growth is verified again at
      this time.

PMID- 9772351
TI  - Signal transduction pathways in guinea pig sperm.
AB  - Trifluoperazine (TFP), the antagonist of calmodulin (CaM), significantly
      stimulated the capacitation and acrosome reaction of guinea pig spermatozoa at
      the concentration of 10-100 mumol/L, independent of the external Ca2+. Forskolin,
      dbcAMP and caffeine evidently promoted the occurrence of acrosome reaction of
      spermatozoa at early capacitation stage (5 h) in nonsynchronous system but not in
      synchronous system. If the spermatozoa were capacitated for 15 h in synchronous
      system, the above three drugs significantly stimulated acrosome reaction in a
      Ca(2+)-independent manner. Protein kinase C activators, i.e. phorbol 12-myristate
      13-acetate (PMA) and phorbol 12,13-dibutyrate (PDB) did not influence the
      occurrence of acrosome reaction of spermatozoa at early capacitation stage, but
      significantly increased the acrosome reaction rate in capacitated spermatozoa in
      a Ca(2+)-independent manner. In contrast, PKC inhibitor staurosporine
      significantly inhibited the occurrence of acrosome reaction.

PMID- 9772352
TI  - Synergic effects of NO and oxygen free radicals in the injury of ischemia
      reperfused myocardium--ESR studies on NO free radicals generated from ischemia
      reperfused myocardium.
AB  - The ESR signal of NO bound to hemoglobin was detected during the ischemia
      reperfusion of myocardium with low temperature ESR technique, and the synergic
      effects of NO and oxygen free radicals in the injury of the process were studied
      with this technique. Oxygen free radicals and NO bound to beta-subunit of
      hemoglobin (beta-NO complex) could be detected simultaneously in the ischemia
      reperfused myocardium. Those signals could not be detected from the normal
      myocardium even in the presence of L-arginine. However, those signals could be
      detected and were dose-dependent with L-arginine in the ischemia-reperfused
      myocardiums and the signal could be suppressed with the inhibitor of NO
      synthetase, NG-nitro-L-arginine methylester (NAME). Measurement of the activities
      of lactate dehydrogenase (LDH) and creatine kinase (CK) in the coronary artery
      effluent of ischemia-reperfused heart showed that L-arginine at lower
      concentration (< 1 mmol/L) could protect the heart form the ischemia-reperfusion
      injury but at higher concentration aggravate the injury. Addition of NAME to the
      reperfusion solution could also protect the myocardium. Addition of xanthine
      (X)/xanthine oxidase (XO) or Fe2+/H2O2 to the reperfusion solution increased the
      production of NO and oxygen free radicals and the ischemia-reperfused injury
      simultaneously. Addition of superoxide dismutase (SOD) and catalase decreased the
      production of NO and oxygen free radicals and the ischemia-reperfusion injury.

PMID- 9772353
TI  - Anchoring of c-myc on nuclear matrix proteins in process of mouse thymic T
      lymphocyte proliferation induced by ConA.
AB  - Isolation and characterization of functional nuclear matrix proteins involved in
      DNA anchoring and gene expression is one of the major subjects of current nuclear
      matrix research. Southwestern blotting (DNA-protein hybridization) was applied to
      studying the anchoring of c-myc on the nuclear matrix proteins in mouse thymic T
      lymphocytes. The results showed that c-myc bound to the lamin, p34 and p36
      nuclear matrix proteins specifically. In the process of mouse thymic PNA-T
      lymphocytes proliferation induced by ConA, the anchoring of c-myc on p34 and p36
      nuclear matrix proteins changed dynamically.

PMID- 9772354
TI  - Glutamate-induced swelling of cultured astrocytes is mediated by metabotropic
      glutamate receptor.
AB  - The effects of glutamate and its agonists and antagonists on the swelling of
      cultured astrocytes were studied. Swelling of astrocytes was measured by [3H]-O
      methyl-D-glucose uptake. Glutamate at 0.5, 1 and 10 mmol/L and trans-1
      aminocyclopentane-1, 3-dicarboxylic acid (trans-ACPD), a metabotropic glutamate
      receptor (mGluR) agonist, at 1 mmol/L caused a significant increase in astrocytic
      volume, whereas alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA)
      was not effective. L-2-amino-3-phosphonopropionic acid (L-AP3), an antagonist of
      mGluR, blocked the astrocytic swelling induced by trans-ACPD or glutamate. In
      Ca(2+)-free condition, glutamate was no longer effective. Swelling of astrocytes
      induced by glutamate was not blocked by CdCl2 at 20 mumol/L, but significantly
      reduced by CdCl2 at 300 mumol/L and dantrolene at 30 mumol/L. These findings
      indicate that mGluR activation results in astrocytic swelling and both
      extracellular calcium and internal calcium stores play important roles in the
      genesis of astrocytic swelling induced by glutamate.

PMID- 9772356
TI  - [Persistence is a matter of great importance].

PMID- 9772355
TI  - Urokinase mutant with better fibrin-specificity.
AB  - A 150-156 amino acids-deleted single-chain urokinase-type plasminogen activator
      (dscu-PA) and its recombinant wild-type counterpart (rscu-PA) were both expressed
      in Escherichia coli. After denaturation and renaturation in vitro, the expressed
      products were both purified to a single silver-stained band by means of IgG
      affinity chromatography. After activation by plasmin, similar enzymatic constants
      based on the hydrolysis of synthetic substrate S2444 by the two-chain molecular
      forms of dscu-PA and rscu-PA, or native tcu-PA were observed, suggesting that no
      impairment had been exerted on the catalytic active site of dtcu-PA by the 150
      156 amino acids deletion. In both in vitro fibrin-clot and 125I-fibrin sepharose
      lysis tests, dtcu-PA showed a significantly higher fibrinolytic activity than
      rtcu-PA or rscu-PA. Hardly any effect on the concentration of fibrinogen in
      plasma was found in dtcu-PA. It was concluded that dtcu-PA had a higher fibrin
      specificity and that tcu-PA could be provided with better fibrin specificity by
      means of mutation.

PMID- 9772357
TI  - [The individualization of activities of blood vessels].
AB  - The functional activities of blood vessels in various organs have their own
      characteristics, named individuality of blood vessel. One of the most outstanding
      characteristics is that the responses of blood vessels in various organs to the
      same stimulation are different, even contradictory. This physiological
      characteristic of the blood vessel guarantees that the blood vessel can make
      adjustable responses in varying parts and under different conditions to fulfil
      the functional tasks of circulatory system and to meet the demands of blood
      supply of recipient organs. The study of vascular individualization would benefit
      to explain the mechanism of blood vessel activities and is also important in the
      study of pathogenesis of vascular diseases. This paper gives a brief description
      on the vascular mechanisms contributing to the individualization of blood vessel.

PMID- 9772358
TI  - [The discovery of a novel opioid-receptor-like receptor and its endogenous
      ligand].
AB  - A novel member of the opioid receptor family (orphan ORL receptor) was cloned in
      1994, followed by the discovery of its endogenous ligand OFQ or nociceptin in
      1995. ORL receptor has 50% homology with conventional opioid receptor, and OFQ is
      structurally homologous with dynorphin A. Whether the two systems are
      functionally antagonistic or synergistic with each other is a subject of future
      research.

PMID- 9772359
TI  - [Advance of gene therapy for neurological diseases by direct in vivo gene
      transfer].
AB  - Gene therapy for neurological diseases is a rapidly expanding field in
      neurosciences. It has been demonstrated that some viral vectors from HSV-1
      (herpes simplex virus type 1), Ad (adenovirus) and AAV (adeno-associated virus)
      can transfer foreign genes into nondividing cell types (including neurons). In
      addition, physical/chemical methods are also used in direct in vivo gene
      transfer. The direct gene transfer techniques will open a new way to study
      neurophysiology, neuropathology and therapy for neurological diseases at
      molecular level. They will hopefully lead to surprising progress in gene therapy
      for neurological diseases.

PMID- 9772360
TI  - [Extracellular matrix].
AB  - Extracellular matrix is composed of four families: collagens, proteoglycans,
      elastin and extracellular matrix structural glycoproteins. The extracellular
      matrix should not be viewed as merely providing strength and physical support for
      tissues and organisms. It is now quite clear that this matrix exerts profound
      influence on both the behaviour (e.g. adherence, spreading, and migration) and
      the pattern of gene expression of the cells. Extracellular matrix research is an
      active field in biology.

PMID- 9772361
TI  - [Transcriptional regulation by CREB and proteins of CREB family].
AB  - CREB (cAMP-responsive element binding protein), which can be activated after
      phosphorylation by protein kinase A, plays an important role in cAMP-induced gene
      expression. Several recent studies have suggested that a co-activator designated
      as CREB binding protein (CBP) is crucial in mediating the transcriptional
      activity of CREB. In nervous system, in addition to playing a role in
      neurotransmitter-induced gene transcription, CREB may take part in mediating
      neurotrophin signals that ultimately lead to such cellular responses as
      proliferation, differentiation and survival.

PMID- 9772362
TI  - [Molecular mechanisms of exocytosis].
AB  - Biochemical and pharmacological characterization of small synaptic vesicle (SSV)
      membrane proteins and genetic studies of yeast secretion mutants led to the
      identification of an exocytotic fusion complex. The Sollner-Rothman SNARE
      hypothesis has led to remarkable progresses in the understanding of the molecular
      mechanisms of neurotransmitter release, endocrine and exocrine cell secretion.

PMID- 9772363
TI  - [Cardiovascular effects and underlying mechanisms of adenosine and its
      analogues].
AB  - The present work was aimed to define the cardiovascular effects and underlying
      mechanisms of adenosine and its analogues. The results showed that (1) adenosine
      and 2-chloroadenosine could induce an initial increase in MAP mediated by the
      adenosine A2 receptors in carotid body chemoreceptor, and a subsequent decrease
      in MAP, being attributed to the adenosine A1 receptors in heart and A2 receptors
      in blood vessels; (2) N6-cyclopentyladenosine (CPA, a selective adenosine A1
      receptor agonist) inhibited the electrophysiological activity of pacemaker cells
      in sinoatrial node; (3) CPA markedly attenuated the development of early
      afterdepolarization, delayed afterdepolarization and triggered activity induced
      by isoproterenol; (4) endogenous adenosine might play an important role in the
      generation of anoxic bradycardia; (5) activation of adenosine receptors along
      with an increase in adenosine receptor density during the course of ischemic
      preconditioning might provide the protective effect on the ischemic heart injury;
      (6) the cardiovascular effects of adenosine and its analogues were mainly
      mediated by activation of ATP sensitive K+ channels coupled to adenosine
      receptors.

PMID- 9772364
TI  - [A study on the cumulative effect of repeated electroacupuncture on chronic
      pain].
AB  - Clinical and animal studies were performed to evaluate the effect of repeated
      transcutaneous electric nerve stimulation (TENS) applied on acupoints of pain
      patients and the effect of repeated electroacupuncture (EA) at acupoints of the
      rat on experimental arthritic pain models. Attempts were also made to evaluate
      whether substance P (SP), cholecystokinin octopeptide (CCK-8), and met5
      enkephalin (MEK) are involved in the mechanism of the cumulative effect of
      repeated EA on experimental arthritis using neuropharmacological (receptor
      antagonists) and neurochemical (radioimmunoassay, RIA) approach. The main results
      show that repeated TENS of 100 Hz relieves spinal spasticity in a cumulative
      manner, while TENS of 2/15 Hz is effective in relieving chronic pain. In animal
      chronic pain models, repeated EA suppressed the hyperalgesia in arthritic rats in
      a cumulative manner. Further studies revealed that in pain patients there was a
      plastic change in the release and metabolic rate of spinal opioid peptides. In
      arthritic rats there was also a change in the releasing rate of spinal SP, CCK-8,
      and MEK as compared to control rats, an effect modulated by repeated EA. These
      plastic changes occured under chronic pain condition and their modulation by
      repeated acupoint stimulation may explain the mechanisms of the cumulative effect
      of acupuncture on chronic pain.

PMID- 9772365
TI  - [The role of fibrinogen in the pathogenesis of artherosclerosis and the
      mechanisms of its action].
AB  - On rabbit artherosclerosis (AS) model induced by feeding high-cholesterol, we
      found that the level of plasma fibrinogen (Fg) was increased early. There was a
      positive correlation between the level of plasma Fg and cholesterol. By means of
      immunohistology analysis in vascular AS plaque, it was found that Fg and its
      degradation products were diffusely distributed beneath endothelium and in
      vascular matrix. Fg itself and its soluble metabolic products did not stimulate
      the proliferation of cultured vascular smooth muscle cell (SMC), but insoluble
      fibrin (Fb) converted from Fg stimulated SMC growth, collegen synthesis,
      intracellular cholesterol accumulation and endothelin release in a dose-dependent
      manner. In addition, Fg inhibited NO synthesis. The results suggest that Fb is an
      important pathogenetic factor of AS. Our studies also showed that the effect of
      Fb on SMC growth was dependent on extracellular Ca2+ and was mediated by protein
      kinase C pathway.

PMID- 9772366
TI  - [Hepatocyte growth factor is an important signal exchanger between mesenchyme and
      epithelia during development].

PMID- 9772367
TI  - [Ca2+ receptor in cell membrane].

PMID- 9772368
TI  - [The function and application of vascular endothelial growth factor].

PMID- 9772369
TI  - [Mitogen-activated protein kinase involved in intracellular signal transduction].

PMID- 9772371
TI  - [Function of p16 gene and correlation of p16 with human cancer].

PMID- 9772370
TI  - [Synthesis and release of neuropeptides in immune system].

PMID- 9772372
TI  - [A presynaptic Ca(2+)-binding protein--synaptotagmin].

PMID- 9772373
TI  - [C-type natriuretic peptide: a novel cardiovascular active substance].

PMID- 9772374
TI  - [Nitric oxide and neurological diseases].

PMID- 9772375
TI  - [Virus infection and atherosclerosis].

PMID- 9772376
TI  - [Opportunities and struggle in my study].

PMID- 9772377
TI  - [Heart rate and blood pressure variability: analytical methods, physiological
      significance, and its applications].
AB  - This paper reviews the literature on the methodological issues relevant to signal
      processing, computation, and clinical applications of heart rate (HR) and blood
      pressure (BP) variability. Linear techniques for both single signal and relations
      between the signals, and clinical role of HRV and BPV analysis are examined. Some
      recent studies in this field are also mentioned.

PMID- 9772379
TI  - [Mechanisms of the calcium influx across the plasma membrane].
AB  - The Ca2+ influx is mainly mediated by voltage-dependent Ca2+ channels and store
      depletion-dependent Ca2+ channels. The former, which mainly acts to regulate Ca2+
      influx in excitable cells, is relatively clear; However, the later, which mainly
      functions in nonexcitable cells, remains enigmatically complicated. Following
      activation of the intracellular Ca2+ store, the depletion of the store provides a
      signal for activating Ca2+ entry across the plasma membrane via presently unknown
      mechanisms. This paper reviews the rapid progress in this field.

PMID- 9772378
TI  - [Research progress on the glia cell line-derived neurotrophic factor].
AB  - Glia cell line-derived neurotrophic factor (GDNF) is a novel type of neurotrophic
      factor cloned in 1993. Recent research revealed that it may have potential
      application in the treatment of Parkinson's disease and motor neuron diseases.
      This short review summarized the character of the protein, gene structure, tissue
      distribution, and its physiological functions and pathological implications.

PMID- 9772380
TI  - [The role of adenosine in the central nervous system].
AB  - Adenosine is one of the normal elements in body fluid including extracellular
      fluid within the CNS. Its normal level is 0.03-0.3 mumol/L. When ATP's metabolism
      loses balance, for example, during ischemia, the level of adenosine increases
      dramatically, may reach as much as 1000 times of the normal. Adenosine plays many
      physiological and pathological roles in CNS via its receptors. It is recognized
      as an inhibitory neuromodulator playing a neuroprotective role in CNS.

PMID- 9772381
TI  - [Cell cycle and apoptosis].
AB  - The progression of cell cycle in embryonic cells from oceanic bionts to
      mammalians is initiated, promoted and terminated under the regulation of cell
      cycle gene products, named cyclins, and a p34 (cdc 2). Besides, oncogene (proto
      oncogene) products such as p53 and pRB also directly regulate the progression of
      cell cycle. However, the p34 (cdc 2) which promotes the mitotic cell division
      also initiates the apoptosis of certain cells. Therefore, mutations of genes that
      regulate the normal progression of cell cycle would cause cells in the cell cycle
      undergoing either apoptosis or uncontrollable proliferation.

PMID- 9772382
TI  - [The central mechanism of corticoids in the incidence of stress-induced
      hypertension].
AB  - We observed that in rats during the incidence of hypertension induced by stress,
      an increase in the plasma concentrations of catecholamines, corticosterone,
      glucose and lipids is parallel with an elevation of blood pressure and heart
      rate. Microinjection of corticoids into the rVLM elicits an effect of pressor,
      tachycardia and enhancement of pressor response to stimulation of the defense
      area, this may be one of the important causes in the incidence of stress-induced
      hypertension. This effect is taken place by a rapid membrane effect of the
      corticoids on the cardiovascular neurons in the rVLM, which is related to an
      abnormal enhancement of cholinergic activity and activation of calcium channel.
      Whereas NO plays an inhibitory effect on the cardiovascular neurons in the rVLM.

PMID- 9772383
TI  - [Chemical anatomy of the nociceptive transmission and modulation in the spinal
      dorsal horn].
AB  - The present study had been made to study the distribution and synaptic
      characteristics of primary afferent C fibers and the normal chemical architecture
      of some neurotransmitters in spinal dorsal horn. The changes of the
      neurotransmitters with acute nociceptive stimulation were measured
      quantitatively. We demonstrated the synaptic relationships among primary afferent
      C fibers, inhibitory interneurons and nociceptive dorsal horn neurons and
      discussed their function in nociceptive transmission and modulation. These
      results provide evidence that acute pain evolved co-release of substance P and
      glutamate from C-fiber terminals may constitute a driving force for secondary
      activation of ascending projection neurons or of internal GABAergic
      antinoceciptive system directly via their receptors in the dorsal horn of the
      spinal cord.

PMID- 9772384
TI  - [Effects of efferent neurotransmitter acetylcholine and cochlear active substance
      ATP on cochlear outer hair cells].

PMID- 9772385
TI  - [Transforming growth factors and cancer].

PMID- 9772386
TI  - [Role of nucleus basalis magnocellularis cholinergic neuron in cognition].

PMID- 9772387
TI  - [Progress in the study of actions of cardiac sympathetic nerve].

PMID- 9772388
TI  - [Oncogenes and function of the gonads].

PMID- 9772389
TI  - [Hypothalamic LHRH pulse generator].

PMID- 9772390
TI  - [beta-Amyloid protein and Alzheimer's disease].

PMID- 9772391
TI  - [Thermoregulation mechanisms of brown adipose tissue].

PMID- 9772392
TI  - [Metallothionein and carcinogenesis].

PMID- 9772393
TI  - [Properties and significance of the chloride current in mammalian ventricular
      myocytes].

PMID- 9772394
TI  - [Advances in cardiac L-type calcium channel].

PMID- 9772395
TI  - [Correlation between alteration of the APC gene and human cancer].

PMID- 9772396
TI  - [Control of catecholaminergic neurotransmitters on the secretion of gonadotropin
      releasing hormone].

PMID- 9772397
TI  - [Long-term potentiation in mammalian visual cortex].

PMID- 9772398
TI  - Women's health in the People's Republic of China: some challenges of
      modernization.
AB  - OBJECTIVE: To identify aspects of the health of Chinese women throughout their
      lifespan which may paradoxically be threatened by modernization and to suggest
      relevant interventions through medical practice, education and research to meet
      these challenges. DATA SOURCES: Six risk areas were selected as examples: infant
      sex ratios; tobacco use by girls; respiratory illness plus anemia; psychosocial
      stress; osteoporosis; and dementia. Articles and other databases, through article
      citations, and through consultations with Chinese medical professionals. DATA
      SELECTION: Studies were selected which described clinical investigations, health
      care policy, or conditions of women in the People's Republic of China (PRC).
      Preference (but not exclusivity) was given to articles in internationally
      available publications, in English, and to authors working in the PRC. DATA
      EXTRACTION: Study quality, specific descriptive information concerning
      population, samples, and outcome measures were evaluated. DATA SYNTHESIS: Data
      documenting the present and future significance of these health threats are
      described, and current and potential interventions to address these problems
      through medical practice, education and research are outlined. CONCLUSION:
      Important issues in women's health are currently recognized in the PRC; problems
      occur in assigning priorities in the face of a large population and limited
      resources. The Chinese medical community plays a central role in developing and
      carrying out interventions to protect and promote women's health.

PMID- 9772399
TI  - Spatiotemporal characteristics of central otolith neurons.
AB  - PURPOSE: To review the spatiotemporal behaviours of central otolith neurons in
      decerebrate animals. DATA SOURCES: Laboratory of Neurophysiology, Department of
      Physiology, Faculty of Medicine, The University of Hong Kong. DATA EXTRACTION:
      Results of key research findings from 1992 to 1997. RESULTS: With constant
      velocity colckwise (CW) and counterclockwise (CCW) off-vertical axis rotations as
      stimuli to the otolith organs, neurons in the vestibular nuclei and medullary
      reticular formation showed characteristic spatiotemporal behavious. One
      dimensional neurons showed symmetric and stable bidirectional response
      sensitivities (delta) to change in velocity while two-dimensional neurons showed
      asymmetric and variable delta to velocity. This CW-CCW asymmetry to bidirectional
      rotations may provide directional coding in the modulation of neural signals.
      Vestibular nuclear neurons also displayed distinct spontaneous discharge patterns
      at the stationary and earth-horizontal position, indicating that one- and two
      dimensional neurons belong to physiologically distinct etities. These
      spatiotemporal behavious of the vestibular nuclear neurons were also shown to be
      precisely controlled by imputs from the vestibulocerebellum and/or bilateral
      otoliths. In both the vestibular nucleus and the reticular formation, the best
      response orientations of one-dimensional neurons and the orientations of the
      maximum response vector of two-dimensional neurons were found to point in all
      directions close to the horizontal plane, indicating that all head orientations
      on this plane are encoded across an ensemble of neurons. CONCLUSION: Otolith
      evoked behaviours of the one-dimensional and two-dimensional neurons constitute
      an important element for the recognition of the direction and orientation of head
      motion in space.

PMID- 9772400
TI  - Comparative study of the effects of ouabain and digoxin on blood pressure of
      rats.
AB  - OBJECTIVE: To compare the effect of ouabain on the blood pressure of rats with
      that of digoxin to find the evidences of the relationship between endogenous
      ouabain (EO) and development of hypertension. METHODS: Sprague-Dawley rats, which
      were divided into 3 groups, were infused with ouabain (23 x 75 micrograms.kg
      1/day, i.p.), digoxin (36 x 84 micrograms.kg-1/day, i.p.) and normal saline (NS)
      once a day respectively. Systolic blood pressure and body weight were recorded
      weekly. Five weeks later, rats of ouabain group were randomly assigned to three
      infusion subgroups: Oc group, continued with ouabain infusion; Od group, added
      digoxin (73 x 68 micrograms.kg-1/day, i.p.) and Os group, stopped administration
      of ouabain. Another week later, direct blood pressure was recorded in aorta.
      Systolic and diastolic cardiac function, plasma renin activity and aldosterone
      levels of all the rats were measured. RESULTS: After a latent period of one week,
      blood pressure of Ouabain group increased significantly [95.4 +/- 11.8 mmHg (1
      mmHg = 0.133 kPa) at the beginning of the experiment vs 122.5 +/- 16.9 mmHg at
      the end of week 6, P < 0.05] with normal plasma renin activity and higher
      aldosterone (1.28 +/- 0.45 ng/ml vs 0.69 +/- 0.27 ng/ml, P < 0.05). The blood
      pressure decreased after either withdrawal of ouabain or addition of digoxin
      (116.3 +/- 14.4 mmHg vs 100 +/- 10.7 mmHg, P < 0.05; 123.9 +/- 13.9 vs 103.3 +/-
      10.5 mmHg, P < 0.05, respectively). No difference of blood pressure was found
      between the digoxin and NS group. CONCLUSIONS: Our results suggested that EO
      might be one of the causes of the development of hypertension. Aldosterone might
      play some role in the mechanism of ouabain-induced hypertension. Digoxin can not
      induce hypertension. There is a great difference between the effect of ouabain
      and digoxin on the blood pressure. Moreover, digoxin can reverse the hypertension
      induced by ouabain.

PMID- 9772401
TI  - Alterations in renal function in patients with obstructive sleep apnea syndrome
      and effects of continuous positive airway pressure.
AB  - OBJECTIVE: To assess renal function in patients with obstructive sleep apnea
      syndrome (OSAS) during two nights when they were untreated and treated with
      continuous positive airway pressure (CPAP). METHODS: Tubular function was
      estimated on the basis of the renal lithium clearance and its derived formulae,
      urinary osmolality, osmolal clearance and free water clearance; while glomerular
      function was evaluated by endogenous creatinine clearance. Twenty patients with
      OSAS and sixteen normal controls were studied. RESULTS: The untreated patients
      with OSAS had significantly lower fractional proximal tubular sodium reabsorption
      (59.1% +/- 7.1%, P < 0.001 vs controls), lower fractional distal tubular sodium
      reabsorption (93.8% +/- 1.7%, P < 0.05 vs controls) and urinary osmolality (573.0
      +/- 107.9 mosm.kg-1, P < 0.05 vs controls). The absolute distal tubular
      reabsorption rate of sodium and osmolal clearance in the untreated patients were
      higher 47.0 +/- 26.0 mmol.L-1 and 25.0 +/- 4.1 ml.L-1; P < 0.01 and P < 0.05
      respectively vs controls). During CPAP-treated nights all abnormal renal function
      indexes in the OSAS patients restored to normal control values (P > 0.05).
      CONCLUSIONS: The natriuresis and diuresis of OSAS patients were due to the
      decrease in proximal and distal tubular sodium reabsorption and in tubular
      concentration ability during their nocturnal sleep and were returned to normal by
      CPAP therapy.

PMID- 9772402
TI  - Clinical and biological relevance of flow cytometric determination of P
      glycoprotein expression in acute non-lymphocytic leukemia.
AB  - OBJECTIVE: To evaluate the characteristics of P-glycoprotein (P-gp) expression of
      acute non-lymphocytic leukemia (ANLL) at different status and the prognostic and
      biological features in ANLL at diagnosis. METHODS: Monoclonal antibody UIC2 and
      indirect immunofluorescence assay by flow cytometry were used to determine P-gp
      expression of 169 patients with ANLL, including 152 previously untreated, 7
      refractory and 10 at remission. RESULTS: P-gp was expressed in 28.9% of the
      previously untreated ANLL cases and P-gp was lower than that in 71.4% of the
      refractory cases (P < 0.05). No P-gp expression was found in the patients at
      remission. For previously untreated AN-LL, P-gp was highly expressed in hybrid
      acute leukemia (66.7%) and acute monoblastic leukemia (47.4%). P-gp expression
      was highly associated with surface markers [cluster of differentiation (CD) 34,
      CD7, CD14, CD42b and CD61] and unfavorable cytogenetic abnormalities. About 23%
      of P-gp-ANLL obtained complete remission, which was significantly lower than that
      (76%) in P-gp-cases. CONCLUSIONS: P-gp expression is higher in refractory ANLL
      cases than that in cases at diagnosis or at remission. P-gp is an index of poor
      prognosis in adults with ANLL. P-gp+ ANLL cases have unique clinical and
      biological characteristics.

PMID- 9772404
TI  - Evaluation of transforming growth factor beta and bone morphogenetic protein
      composite on healing of bone defects.
AB  - OBJECTIVE: To evaluate the effect of transforming growth factor-beta/bone
      morphogenetic protein (TGF-beta/BMP) composite on the healing of large segmental
      bone defects and to discuss the interaction between TGF-beta and BMP during bone
      repair. METHODS: A 1.5 cm segmental defect was made in the mid-upper part of the
      radial shaft of 48 adult rabbits. The defects were filled with implants of TGF
      beta/carrier, BMP/carrier or TGF-beta/BMP/carrier separately. 120 micrograms of
      purified bovine TGF-beta and 12 mg of BMP were used in the composite. The defects
      were examined radiographically and histologically at 4, 8, 12 and 16 weeks post
      operation. RESULTS: In the group filled with TGF-beta/BMP composite, the defect
      areas were bridged at 4 weeks, with callus of uniform radiodensity. Cortices of
      the cut ends were obscured by new bone. By 16 weeks post-operation, the defects
      were bridged by uniform new bone and the cut ends of the cortex could not be seen
      in all groups. In group of BMP/carrier, the defects were filled with more
      irregular woven bone callus than in other two groups. TGF-beta/BMP implanted
      defects in animals killed at 16 weeks showed histologically new lamella and woven
      bone that was formed in continuity with the cut ends of the cortex. Medullar
      canal was recanalized and contained marrow elements with normal appearance.
      CONCLUSIONS: These data demonstrate not only the synergistic action between TGF
      beta and BMP in the process of bone healing, but also a better effect of TGF
      beta/BMP composite than single TGF-beta or BMP on bone repair, especially in the
      early stage of bone repair process.

PMID- 9772403
TI  - Kinetics of plasma cytokines and its clinical significance in patients with
      severe trauma.
AB  - OBJECTIVE: To examine the kinetics of plasma tumor necrosis factor alpha (TNF
      alpha), interleukin-6 (IL-6) and interleukin-8 (IL-8) in patients with severe
      trauma and to discuss their relationship with organ damage and endotoxemia.
      METHODS: Seventeen patients (10 men and 7 women) with severe trauma were selected
      in this study. Their mean age was 37.9 +/- 11.9 years. All patients were divided
      into two groups according to injury severity score (ISS): group I with ISS from
      16-25 (18.8 +/- 2.9, n = 10) and group II with ISS more than 25 (34.3 +/- 8.3, n
      = 7). Ten young healthy volunteers (6 men and 4 women) were used as controls.
      Plasma TNF alpha and IL-8 levels were assayed with enzyme-linked immunosorbent
      assay. IL-6 activity in the plasma was determined by bioassay with IL-6-dependent
      cell-line 7TD1. Limulus amebocyte lysate chromogenic test was used for plasma
      endotoxin assay. RESULTS: Plasma cytokine levels in patients with trauma had a
      successively significant increase. Plasma TNF level increased earlier. Increases
      in plasma IL-6 and IL-8 occurred later. All the increases were significantly
      correlated with the severity of trauma and organ damage after trauma. In
      addition, obvious endotoxemia occurred at the early stage of trauma and was
      significantly correlated with the severity of trauma and the levels of plasma TNF
      alpha, IL-6 and IL-8. CONCLUSIONS: Release of TNF alpha, IL-6 and IL-8 can be
      significantly increased in patients with severe trauma. The increase may be
      related to massive endotoxin translocation and may play an important role in the
      development of organ damage after trauma.

PMID- 9772406
TI  - Critical care in obstetrical patients: an eight-year review.
AB  - OBJECTIVE: To review the clinical characteristics and outcomes of critically ill
      obstetrical patients and to determine the outcome predictability using the Acute
      Physiology and Chronic Health Evaluation (APACHE) II scoring system. METHODS: A
      retrospective data collection of all obstetrical patients (n = 49) admitted for
      more than 24 hours to the Intensive Care Unit at Kwong Wah Hospital from 1988 to
      1995 was conducted. Demographics, obstetric data, preexistent medical problems,
      diagnosis, days staying in the ICU and ICU related data were recorded for each
      patient. RESULTS: Obstetric admissions to ICU during the study period represented
      0.12% of all deliveries during this period. There was a predominance of
      postpartum admissions and obstetric diagnosis responsible for the patients'
      critical illness. Massive postpartum haemorrhage was the single most common cause
      of ICU admission, representing 53.0% of all patients. Preeclampsia and eclampsia
      (14.3%), anaesthesia related complications (14.3%), and medical diseases
      complicating pregnancy (14.3%) were the other common disease categories for ICU
      admission. Two cases (4.1%) of surgical disease complicating pregnancy were
      admitted. The maternal mortality rate was 5.1 deaths per 100,000 total births, or
      2 maternal deaths in 39,354 total deliveries in this study period. All deaths
      were due to nonobstetric causes. The perinatal mortality rate was 10.0% (5 cases)
      in this study group. CONCLUSIONS: When applying the Acute Physiology and Chronic
      Health Evaluation (APACHE) II scoring system in predicting the final outcome in
      this group of obstetric patients, we found that our obstetric patients requiring
      intensive care had a better outcome than predicted, as expressed by a low
      mortality ratio (0.25).

PMID- 9772405
TI  - Expression and cellular location of endothelin-1 mRNA in rat liver following
      endotoxemia.
AB  - OBJECTIVE: To study the effect of endotoxin on the alteration of the
      transcription, expression and cellular location of endothelin-1 (ET-1) mRNA in
      the hepatic tissue. METHODS: Wistar rats were divided into control and endotoxic
      group. The rats in the control group were injected with saline, and those in the
      endotoxic group with endotoxin at a dose of 10 mg.kg-1 body wt. ET-1 hepatic
      homogenate was assayed by radioimmunoassay at 3, 6, 9, 12 and 24 h after
      endotoxin administration. Dot blot was used to identify and quantify ET-1 mRNA of
      the hepatic tissue. Hybridization of ET-1 of the hepatic tissue was proceeded at
      3, 6, 12 and 24 h after endotoxin administration. RESULTS: ET-1 concentrations
      and the level of ET-1 mRNA increased rapidly and reached the peak at 6 h, and
      remained high at 24 h after endotoxin administration. By in situ hybridization,
      ET-1 mRNA was found in hepatic sinusoids, endothelial cells of portal vein and
      kupffer cells. CONCLUSIONS: Endotoxin may be the principal stimulating factor for
      expression of ET-1 mRNA in hepatic tissue. Endotoxin may affect transcription and
      translation level of ET-1, leading to increase of the synthesis and release of ET
      1. The hepatic vascular endothelial cells, hepatic sinusoids and Kupffer cells
      all synthesize and release ET-1.

PMID- 9772407
TI  - Combination of ultrasound pelvimetry and fetal sonography in predicting
      cephalopelvic disproportion.
AB  - OBJECTIVE: To assess a method of antepartum diagnosis of cephalopelvic
      disproportion by comparing the diameters of fetal head with those of the maternal
      midpelvis. METHODS: Transvaginal ultrasound pelvimetry was performed on 190
      healthy primigravidas with cephalic presentation at 28-35 weeks of gestation, and
      the fetal heads were measured within one week before delivery. The cephalopelvic
      indices of diameter, circumference and area were calculated and compared.
      RESULTS: The index exhibiting the highest degree of accuracy (77.9%) was the
      cephalopelvic index of diameter (CID) defined as the difference between the mean
      diameter of the midpelvis and the fetal biparietal diameter (BPD). Eighty-three
      percent of the cases with CID less than 15.8 mm needed operative delivery, and
      76.2% of the cases with CID more than 15.8 mm underwent vaginal delivery.
      CONCLUSIONS: The CID may be used to identify cephalopelvic disproportion before
      the labor and help obstetricians choose the most appropriate form of delivery in
      an uncomplicated vertex presentation.

PMID- 9772408
TI  - The embryonic development of the human lamina cribrosa.
AB  - OBJECTIVE: To investigate the embryonic development of lamina cribrosa of human
      eyes. METHODS: The lamina cribrosa of 291 eyes were studied including 260 eyes
      taken from embryos and fetus of 7 weeks to full term and 31 eyes from infants
      under 1 year of age by using light microscopy (LMS), scanning electron microscopy
      (SEM), and transmission electron microscopy (TEM). RESULTS: From observations, it
      was found that the development of the lamina cribrosa was lagged behind the
      development of the optic nerve. CONCLUSIONS: In eyes taken from embryos or fetus
      less than 4 months of pregnancy, only ectodermal primordium of the lamina
      cribrosa could be seen. The initial scleral part of the lamina cribrosa began its
      formation in the 5th month of fetus. The fibrous tissue originating from the
      choroid and optic nerve sheath contributed to the formation of the lamina
      cribrosa in the 8th month fetus. At this time, the morphology of the lamina
      cribrosa is similar to that of an adult, however the thickness of the structure
      is still getting increased up to one year after birth.

PMID- 9772409
TI  - Inhibition of vascular smooth muscle cell proliferation by introduction of
      retinoblastoma gene via a recombinant adenovirus vector.
AB  - OBJECTIVE: To investigate the vascular smooth muscle cell (SMC) growth
      suppression by recombinant adenovirus vector expressing a retinoblastoma (Rb)
      protein and to explore a gene therapy approach for vascular proliferative
      disorders including atherosclerosis and artery restenosis. METHODS: A replication
      deficient adenovirus vector encoding a wild-type Rb and AdCMVRb, was constructed
      and transfected into cultured rabbit aortic SMC. The efficiency of gene
      transfection and expression was detected by immunochemical staining and
      polymerase chain reaction. The role of Rb in regulating vascular SMC
      proliferation was observed by cell-counting, [3H] thymidine incorporation, and
      flow cytometry. RESULTS: Wild-type Rb gene transfected effectively into the
      cultured SMC with AdCMVRb can suppress growth factor-stimulated cell
      proliferation through regulation of DNA synthesis and cell cycle progression.
      CONCLUSION: The results demonstrate the potential of adenovirus-mediated Rb gene
      therapy for atherosclerosis and artery restenosis after balloon angioplasty.

PMID- 9772410
TI  - The roles of multimodality treatment and lymphadenectomy in the management of
      esophageal cancer.
AB  - PURPOSE: To review the current status of multimodality treatment and
      lymphadenectomy in the management of esophageal cancer. DATA SOURCES: Literature
      review. STUDY SELECTION: Multimodality treatment and lymphadenectomy in
      esophageal cancer. DATA EXTRACTION: Results in research papers published selected
      by literature search. RESULTS: Numerous studies have been carried out attempting
      to define the roles of various neoadjuvant or adjuvant regimens in the treatment
      of esophageal cancer. These included the use of radiotherapy or chemotherapy
      alone or in different combinations, with or without surgical resection.
      Randomized trials have failed to show significant improvement compared with
      surgical resection alone, although downstaging of disease and benefits on
      subgroups of patients could be demonstrated. Whether the extent of resection can
      influence outcome was tested by varying the surgical approach, and by increasing
      the extent of lymphadenectomy. Although indirect evidence exists suggesting more
      extensive resection may improve long term prognosis, definitive proof is lacking.
      CONCLUSIONS: More well organized randomized controlled trials are needed to
      further elucidate the roles of these approaches in the treatment of esophageal
      cancer.

PMID- 9772411
TI  - Nasopharyngeal carcinoma research in Hong Kong in the past decade.
AB  - OBJECTIVE: To review the research carried out in Hong Kong on nasopharyngeal
      carcinoma (NPC) over the past 10 years. METHODS: The literature published in Hong
      Kong over the past 10 years on nasopharyngeal carcinoma were reviewed in the
      light of other important international publications on the same subject. RESULTS:
      The research carried out in Hong Kong covers etiology, natural behavior,
      treatment and prognosis of NPC. These studies not only elucidated the different
      aspects of NPC, many of these new findings will also guide future directions of
      research. CONCLUSIONS: Major efforts have been made to research into the various
      aspects of NPC with important findings which will translate into better treatment
      results. As this tumor is uncommon in other parts of the world, continued efforts
      to improve the prevention, early diagnosis, treatment and care of this tumor are
      required in China.

PMID- 9772412
TI  - Prenatal ultrasonographic diagnosis of homozygous alpha-thalassaemia-1.

PMID- 9772413
TI  - Oral captopril versus placebo among 14,962 patients with suspected acute
      myocardial infarction: a multicenter, randomized, double-blind, placebo
      controlled clinical trial. Chinese Cardiac Study (CCS-1) Collaborative Group.
AB  - OBJECTIVE: To assess the efficacy of captopril on mortality and morbidity after
      acute myocardial infarction (AMI). METHODS: A total of 14,962 patients entering
      650 hospitals from 30 provinces and autonomous regions of China up to 36 hours
      (mean 16.6 +/- 10.2 hours) after the onset of suspected acute myocardial
      infarction (MI) with no clear contraindications or indications to the study
      treatments (in particular, no persistent hypotension or hypovolemia due to long
      term use of large dose of diuretics) were randomized to use either 4 weeks of
      oral captopril (6.25 mg initial dose, 12.5 mg 2 hours later, and then 12.5 mg
      three times daily) or matching placebo. RESULTS: Captopril was associated with a
      non-significant reduction in 4-week mortality (9.12% vs 9.74%; P = 0.20); but
      incidence of heart failure was significantly reduced among captopril group (17.0%
      vs 18.7%; P = 0.01). The combined end point (death + heart failure) was 1680
      (21.5%) in captopril group and 1733 (23.1%) in placebo group (P = 0.02). Anterior
      wall infarction of captopril treated group was found to have lower mortality
      (8.6% vs 10.2%, P = 0.02). Captopril treated group with a heart rate (HR) > or =
      60/min at entry showed significantly lower mortality than placebo group (9.2% vs
      10.7%; P = 0.01). There was a significant excess of hypotension, mostly after the
      start of treatment, but no evidence of any adverse effect on early mortality.
      CONCLUSIONS: The angiotensin converting enzyme inhibitors (CEI) therapy started
      early in acute MI prevents about 6 deaths per 1000 treated, and about 15 deaths
      due to heart failure per 1000 in the 1st 4 weeks with greater benefits. In
      anterior myocardial infarction group it prevents 16 deaths per 1000 with nearly
      no benefit for the inferior infarction group. Due to the parasympathetic mimic
      effect, CEI should be used carefully in inferior infarction patients especially
      when HR is slow or heart block and hypotension are present.

PMID- 9772414
TI  - Multicenter clinical trial of thrombolytic therapy in 1,406 patients with acute
      myocardial infarction. Collaborative Group of Clinical Trial for Urokinase
      Therapy.
AB  - OBJECTIVE: To investigate the clinical efficacy and safety of intravenous
      thrombolytic therapy of Urokinase Tech-Pool (UKTP) in acute myocardial infarction
      (AMI). METHODS: The data were collected from the 148 participating hospitals from
      November, 1994 to April, 1996. A total of 1,406 patients with AMI were analyzed
      to evaluate the clinical efficacy, side effects and mortality of UKTP. The
      patency of the infarct-related artery (IRA) was evaluated in 124 patients by
      coronary artery angiography (CAG) 90 minutes after the onset of UKTP infusion.
      RESULTS: The reperfusion rate in IRA was 73.5% by clinical standards. The patency
      rate was 72.6% by CAG. The total mortality during the first 5 weeks was 7.8%
      (109/1,406). The rate of minor bleeding was 10.2% (143/1,406), of major bleeding
      0.43% (6/1,406) and of intracranial hemorrhage 0.50% (7/1,406). In elderly
      patients (> 75 years old), UKTP was as effective and safe as in younger patients
      (< 65 years old). Late thrombolytic therapy with UKTP (> 6 hours after the onset
      of symptom) was still effective. The appropriate dosage of UKTP might be 150
      million units of infusion within 30 minutes. CONCLUSION: UKTP is an effective,
      reliable and safe agent in the thrombolytic therapy of AMI.

PMID- 9772415
TI  - Effects of removing circulatory tumor necrosis factor by immunoadsorption on
      experimental endotoxin shock animals.
AB  - OBJECTIVE: To evaluate the effects of removing circulatory tumor necrosis factor
      (TNF) by immunoadsorption on endotoxin shock animals. METHODS: Sixty New Zealand
      white rabbits were injected intravenously with lethal dose of endotoxin (10
      Billion cfu/kg E. Coli endotoxin) and randomly divided into 3 groups: perfusion
      group, hemoperfusion started at 1 hour after injecting endotoxin through
      immunoadsorbent columns against TNF; pseudoperfusion group, hemoperfusion through
      blank columns; and control group, injected with endotoxin only. The arterial
      pressure, microcirculation of the mesentery, plasma levels of TNF, IL-1, IL-6, IL
      8, nitrite, endothelin-1 (ET-1), alanine aminotransferase (ALT), aspartate
      aminotransferase (AST), creatinine were measured and analyzed and finally the
      survival rate was observed. RESULTS: Plasma levels of TNF were sharply reduced
      after immunoadsorption. Moreover, release of IL-1, IL-6, IL-8, NO and ET-1 were
      also attenuated. Hemodynamic abnormalities could be improved and survival rate
      ameliorated significantly. CONCLUSION: Specific immunoadsorption of circulating
      TNF might be a new and effective therapy for endotoxin shock.

PMID- 9772416
TI  - Effects of recombinant human transforming growth factor-beta 1 or/and interleukin
      6 on growth inhibition and proto-oncogene c-myc expression in human leukemia
      cells.
AB  - OBJECTIVE: To examine the effect of recombinant human transforming growth factor
      beta 1 (rhTGF-beta 1) alone or recombinant human interleukin 6 (rhIL-6) alone or
      in combination on proliferation inhibition of the human leukaemia cell line.
      METHODS: In the present study, using the human monoblastic cell line (U937) and
      human promyelocytic cell line (HL60) as an in vitro model, we analyzed the effect
      of two cytokins on proliferation inhibition with rate of 3H-TdR incorporation,
      the cellular content of DNA, DNA indices, the cell cycle and the expression of c
      myc mRNA. RESULTS: With administration of rhTGF-beta 1 and rhIL-6, U937 cell
      growth was inhibited and the rate of 3H-TdR incorporation inhibition was
      increased. There was a decrease in the cellular content of DNA and DNA indices.
      And no change in the cell cycle was observed after administration of rhTGF-beta 1
      or rhIL-6. However, there was an increase in G0/G1 phase cells and a decrease in
      G2M + S phase cells after administration of combination of rhTGF-beta 1 and rhIL
      6. It was also found that rhIL-6 could inhibit proliferative responses of HL60
      cells, meanwhile the inhibition could be enhanced by rhTGF-beta 1. The rate of 3H
      TdR incorporation inhibition rose up to 39.89%, and DNA index fell to 1.00
      following induction by rhIL-6 plus rhTGF-beta 1. Furthermore, G0/G1 phase cells
      increased while G2M + S cells decreased. CONCLUSIONS: These results suggest that
      combination of rhTGF-beta 1 and rhIL-6 acted in synergy to inhibit proliferation
      of both U937 and HL60 cell lines. Molecular hybridization test show that rhTGF
      beta 1 alone, rhIL-6 alone or rhTGF-beta 1 and rhIL-6 in combination can inhibit
      U937 and HL60 cells expression of c-myc mRNA in a time and dose dependent manner.
      rhTGF-beta 1 and rhIL-6 in combination synergistically inhibited c-myc
      expression, which may be one of the machanisms for the actions of the two
      cytokines.

PMID- 9772417
TI  - Clinical, pathologic and genetic studies on mitochondrial myopathy,
      encephalopathy, lactic acidosis and stroke-like episodes.
AB  - OBJECTIVE: To study the clinical, pathological and genetic characteristics of
      mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes
      (MELAS). METHODS: Eight cases of MELAS (6 of them were from 2 families) underwent
      clinical study, muscle biopsy, autopsy on one patient, brain biopsy on one
      patient and genetic research. RESULTS: In clinical report the average age of
      onset was 10-22 years old. Four cases from one family were 3 brothers and their
      nephew (sister's son). The death age of the three brothers was 16-20 years. Two
      cases from another family were a brother and a sister. The six patients of the
      two families showed the typical inherited characters of MELAS. The symptoms were
      myoclonic epilepsy, stroke-like episodes, paralysis of limbs, progressive mental
      retardation and neurological deaf. CT showed calcification in globus pallidus and
      MRI demonstrated clearly the abnormal prolongation of T2-weighed signals that
      distributed in frontal, parietal, occipital and temporal cortex as multiple
      focal, cystic and laminar necrotic areas. Pathological studies on brain showed
      multi-focal, cystic, and laminar or spongy necrotic abnormality primarily in gray
      matter of frontal, parental, temporal and occipital cortex. Decrease and loss of
      nerve fibers of the sub-cortical white matters of the lesion areas of cortex and
      calcification of globus pallidus were also observed. Red ragged fibers (RRF) and
      abnormal mitochondron were found by muscle biopsies. A point mutation (A-G
      transition) at nt 4243 in the mitochondrial tRNA Leu (UUR) was confirmed by using
      PCR and Southern Blot. CONCLUSION: Although great progress has been made in the
      clinical, pathological and genetic research of MELAS, the pathogenesis of the
      disease remains further research.

PMID- 9772418
TI  - Electrophysiological forms of Guillain-Barre syndrome in Beijing suburb.
AB  - OBJECTIVE: To recognize different forms of Guillain-Barre syndrome (GBS) in
      northern China. METHODS: Twenty-one cases were found in two counties of Beijing
      suburb from January 1993, to December, 1994. Multiple electrophysiological
      studies including magnetic motor evoked potential, F-wave, motor and sensory
      conduction velocity, blink reflex and needle electromyography were conducted on
      nineteen cases of them. Twelve cases accepted electrophysiological follow-up
      study. RESULTS: Altogether 17 cases showed demyelination features in multiple
      electrodiagnosis. Ten cases of them were accompanied by different extent of
      axonal lesion. Only one case showed main or primary axonal lesion. CONCLUSIONS:
      Demyelination is the main type of pathophysiological lesion of GBS in Beijing
      suburb. Different extent of axonal lesion can appear in some cases, but primary
      and main axonal type is rare in this area.

PMID- 9772419
TI  - Comprehensive analysis of results of surgical treatment of oral tongue carcinoma
      in Hong Kong.
AB  - OBJECTIVE: To evaluate the results of primary surgical treatment of carcinoma of
      oral tongue in Hong Kong. METHODS: Patients who had undergone primary surgical
      treatment of oral tongue carcinoma in Queen Mary Hospital were reviewed. RESULTS:
      There were 112 patients in this study. The first sites of tumor recurrence were
      10 (9%) local, 25 (22%) nodal, 3 (3%) locoregional, 5 (5%) distant, 1 (1%) local
      and distant, 3 (3%) nodal and distant, and 1 (1%) neck extranodal site. Of the 63
      T1-2 N0 M0 patients, the regional recurrence rate was 9% for elective neck
      dissection compared with 47% for "watchful waiting" (Chi-square test, P =
      0.0008). The regional recurrence related mortality was 3% for elective neck
      dissection compared with 23% for "watchful waiting" (Fisher's test, P = 0.02).
      The 5-year actuarial survival rate was 86% for elective neck dissection compared
      with 55% for "watchful waiting" (Wilcoxon, P = 0.01). CONCLUSIONS: Local and
      regional recurrences were the main sites of treatment failure. Elective neck
      dissection has significant benefits in the reduction of regional failure and
      improvement of survival. Elective selective I-III neck dissection have to be
      considered in patients with stage I and stage II oral tongue carcinoma.

PMID- 9772420
TI  - Genital Ureaplasma urealyticum infection in varicocele-related infertility.
AB  - OBJECTIVE: To assess the existence of a possible infectious factor in varicocele
      related infertility. METHODS: A total of 925 seminal plasmas from 590 infertile
      men with varicocele and 335 infertile patients without palpable varicocele were
      cultured for Ureaplasma urealyticum infection, and routine semen analysis was
      made. RESULTS: The infection rate of Ureaplasma urealyticum in seminal plasmas
      was 48.22%. The asymptomatic genital infection of Ureaplasma urealyticum was
      traced in 329 (55.76%) varicocele men and 117 (34.93%) infertile patients without
      varicocele (control group). A significant quantitative difference in the
      incidence of genital Ureaplasma urealyticum infection between the varicocele and
      control group was observed (P < 0.005) and asthenozoospermia was significantly
      more prevalent in the patients with varicocele than in the other patients (P <
      0.05). CONCLUSIONS: Genital Ureaplasma urealyticum infection may play a role in
      varicocele-related infertility. To prevent future infertility, men with both
      varicocele and genital Ureaplasma urealyticum infection may benefit from early
      evaluation and treatment.

PMID- 9772421
TI  - Study of the expression of the gene encoding Ki-67 antigen in human pancreatic
      cancer using non-radioactive in situ hybridization and immunohistochemistry.
AB  - OBJECTIVE: To investigate, at transcriptional and translational level in situ,
      whether the gene expression of the Ki-67 protein in pancreatic carcinoma
      specimens is altered to get insight of the gene structure and function. METHODS:
      Forty pancreatic cancer, 5 normal pancreatic and 4 chronic pancreatitis tissues
      were used in this experiment. A 435 bp cDNA fragment located in codon 2, exon 13
      of Ki-67 antigen gene was amplified by the polymerase chain reaction (PCR). The
      DIG-labeled cRNA probes were transcribed using a commercial DIG RNA labeling kit.
      Localization of the Ki-67 protein and the specific mRNA was performed by
      combining immunohistochemistry (ICH) with DIG-labeled in situ hybridization
      (ISH). RESULTS: Successful localization of the Ki-67 protein mRNA in pancreatic
      tissue sections, routinely formalin-fixed and paraffin-embedded, was first
      accomplished in this experiment. Analysis of the Ki-67 mRNA transcription in 17
      pancreatic cancer specimens with Ki-67 ICH labeling index > 20% revealed stronger
      mRNA signals in poorly differentiated specimens with Ki-67 index > 50% than in
      well differentiated cases with the ICH labeling index of 20%-50%. A high
      expression of both the mRNA and the protein was observed in pancreatic
      adenocarcinomas with poor differentiation. CONCLUSIONS: This is the first study
      in which the abnormal overexpression of the gene encoding Ki-67 protein was
      detected not only at the protein level, but also at the mRNA level in pancreatic
      tumours. The abnormal overexpression of the Ki-67 protein might be correlated
      with the central part, exon 13, of the gene.

PMID- 9772422
TI  - Early intervention improves intellectual development in asphyxiated newborn
      infants. Intervention of Asphyxiated Newborn Infants Cooperative Research Group.
AB  - OBJECTIVE: To evaluate the effect of early intervention on the intellectual
      development in asphyxiated newborn infants. METHODS: Full term asphyxiated
      infants (Apgar score < or = 6 at 5 minutes after birth) were randomly assigned to
      early intervention group (34 cases) and conventional care (30 cases) group. The
      normal control group consisted of 38 infants. Sex, mother's educational
      background, environmental condition and physical development were not
      significantly different in the 3 groups. Zero to two years early intervention
      program was compiled on basis of the national and foreign material about 1 month
      ahead of average development of the child. It included motor, cognitive, speech
      development and social behavior. Parents were instructed to carry out early
      intervention. RESULTS: At the age of 1.5 years, average score of mental
      development index (MDI) in early intervention group was 14.6 higher than that in
      conventional care group (F = 18.86, P < 0.0001). MDI score in early intervention
      group caught up with that in normal control group (F = 2.17, P > 0.05).
      Conventional care group was 9.7 lower than normal control group (F = 10.14, P <
      0.01). Two of 30 cases (6.7%) in conventional care group was mentally retarded
      while none was mentally retarded in the early intervention group. CONCLUSIONS:
      The results showed that the early intervention could promote intellectual
      development of asphyxiated infants and be of much benefit to the prevention of
      mental retardation.

PMID- 9772423
TI  - Short-term clinical study on a new aqueous humor drainage implant for refractory
      glaucoma.
AB  - OBJECTIVE: To investigate the therapeutic effect of a new aqueous humor drainage
      (HAD) implant made in China for the treatment of refractory glaucoma. METHODS:
      The implant was designed by ourselves and manufactured by Beijing Rubber Products
      Design and Research Institute. From July, 1993 to September, 1995, we observed 40
      patients (41 eyes) with refractory glaucoma treated by implantation surgery,
      including 16 eyes with neovascular glaucoma (NVG) and 25 eyes with non
      neovascular glaucoma (NNVG). RESULTS: The mean period of postoperative follow-up
      was 9.2 (range, from 3-27) months, the intraocular pressure (IOP) was lowered
      from preoperative 7.20 +/- 1.51 kPa to postoperative 2.40 +/- 1.33 kPa in NVG
      group and from preoperative 6.27 +/- 1.07 kPa to postoperative 2.00 +/- 2.93 kPa
      in NNVG group. The success rate was 81% in NVG group and 84% in NNVG group. The
      common postoperative complications were flat anterior chamber, hyphema and
      choroidal detachment. CONCLUSIONS: Our newly designed aqueous humor drainage
      implant is an economical implant in China and one of the alternative and
      effective methods for the treatment of refractory glaucoma. It can be widely used
      in clinics.

PMID- 9772424
TI  - Effects of high intensity impulse noise on ionic concentrations in cochlear
      endolymph of the guinea pig.
AB  - OBJECTIVE: To investigate the effect of acoustic overstimulation on
      concentrations of cations in cochlear endolymph and analyze the relationship
      between the ionic changes in endolymph and the hearing loss. METHODS: The
      endocochlear potentials (EP), K+, Na+ and Ca2+ concentration in cochlear
      endolymph were examined in vivo for normal and 167 +/- 2 dB SPL impulse noise
      exposed groups of guinea pig bored on time course by means of double-barreled ion
      selective microelectrodes. Brain stem auditory evoked potential (BAEP) was used
      to evaluate the auditory function. Ca(2+)-ATPase activity was demonstrated
      cytochemically in the lateral cochlear wall as induced by Ando et al with slight
      modification. RESULTS: The K+ and Ca2+ concentration exhibited significant
      changes in 8-hour groups (P < 0.05 for K+ and P < 0.01 for Ca2+). Then the K+
      concentration was eventually resumed to the initial levels in accordance with the
      EP recovery in 7 days, while during the same period Ca2+ concentration was always
      significantly higher than that in control group (P < 0.01). The BAEP threshold
      shifts were correlated well with changes in ionic concentrations, especially Ca2+
      (P < 0.001), in the endolymph induced by acoustic trauma. Although the normal
      positive EP was observed 7 days after noise exposure, the function of the
      vascular stria was not completely restored as revealed by the fact that the
      Ca(2+)-ATPase was diffused to the apical membrane surface. CONCLUSIONS: Endolymph
      compartment intrinsic mechanism for maintaining ionic composition is seriously
      deteriorated after high impulse noise stimulation. The changes of the unique
      environment of endolymph may play an important role in the mechanism of
      sensorineural hearing loss induced by acoustic trauma.

PMID- 9772425
TI  - Identification of a novel missense mutation in Wilson's disease gene.
AB  - OBJECTIVE: To investigate the allelic heterogeneity of the ATP7B gene in Chinese
      patients with Wilson's disease (WD). METHODS: Exons of the ATP7B gene from 141 WD
      patients' DNA were amplified with polymerase chain reaction (PCR) 887-890.
      Mutations were then screened by single strand conformation polymorphism (SSCP)
      analysis and further identified by sequencing. RESULTS: The molecular structure
      of exon 7 of the ATP7B gene from 141 WD patients was analyzed. The same band
      shift in electrophoretic pattern of 4 cerebral type patients was identified with
      SSCP and subsequently sequenced. The results showed missense mutation at the
      second base of the codon as Ser 662 Cys, which is caused by a C to G
      transversion. CONCLUSIONS: Mutations of the ATP7B gene were investigated for the
      first time in China and a novel missense mutation was identified in four cases.

PMID- 9772426
TI  - The relationship between insulin resistance and abnormality of cellular calcium
      metabolism in patients with essential hypertension.

PMID- 9772429
TI  - [New trends on oncogenes].

PMID- 9772427
TI  - Treatment of cutaneous hemangiomas with low-dose soft x-ray.

PMID- 9772430
TI  - [Inhibitory effect of ganciclovir on the HSV1-tk positive subcutaneous tumors
      transplanted with human ovarian cancer in nude mice].
AB  - OBJECTIVE: To investigate the inhibitory effect in vivo of ganciclovir (GCV) on
      the growth of human ovarian cancer cells (AO) transducted with the thymidine
      kinase gene of herpes simplex virus I type (HSV1-tk). METHODS: Tumors were
      induced in nude mice by subcutaneous injection of AO cells and AO cells carried
      with HSV1-tk gene from China strain (AO/HSV1-tk cells). When the growing tumors
      were visible, GCV was injected daily into the peritoneum of the nude mice.
      RESULTS: The average weights of survived AO/HSV1-tkc tumors and AO tumors treated
      with GCV were 0.087 +/- 0.036 g and 0.661 +/- 0.260 g respectively. Most of the
      survived AO/HSV1-tkc cells treated with GCV were characterized by hypertrophy and
      necrosis, but their nuclear chromatins predominantely took the forms of
      heterchromatins. CONCLUSIONS: GCV could effectively inhibit the growth of HSV1-tk
      positive human ovarian cancer cells in vivo, but the nuclei of the survival tumor
      cells appeared to proliferate actively. As the same results of in vitro
      experiments, this may suggest that HSV1-tk/GCV gene therapeutic system might be
      combined with S-phase chemotherapy to increase the long-term effect.

PMID- 9772431
TI  - [Animal experiment on gene therapy of ovarian cancer by adenovirus-mediated
      thymidine kinase gene transduction and ganciclovir administration in vivo].
AB  - OBJECTIVE: The efficacy and toxicity of adenovirus-mediated transduction of
      herpes simplex virus thymidine kinase gene started by Rous sarcoma virus (ADV/RSV
      tk) followed by administration of ganciclovir (GCV) were studied in vivo.
      METHODS: An animal model of human epithelial ovarian cancer was established in
      nude mice using the serous ovarian adenocarcinoma cell lines Ov-ca-2774, then
      mice were treated by ADV/RSV-Tk and GCV, or GCV and HSV-tk respectively. The
      average survival time of mice and toxicity were assessed. RESULTS: The mice
      treated with GCV or HSV tk alone died from 14.4 +/- 1.7 to 19.3 +/- 3.5 days
      after treatment. The survival time had no difference with control group. The mice
      treated with ADV/RSV-tk followed by GCV lived at least two times longer than
      controls and the difference in both groups was significant. The earlier the
      treatment began, the longer the average survival time was. Treatment efficacy was
      dependent on dose of ADV/RSV-tk and tumor burden of mice. CONCLUSION: ADV/RSV-tk
      gene therapy is a safe and efficient approach to ovarian cancer treatment in the
      experiment.

PMID- 9772432
TI  - [Biologic effects of introduction of wild-type p53 cDNA into a human ovarian
      cancer cell line SKOV-3].
AB  - OBJECTIVE: To study the effects on biologic behavior in cells obtained from human
      ovarian cancer cell line SKOV-3 into which the wild-type p53 cDNA was introduced.
      METHOD: Recombinant eukaryotic expression vector pC53-SN3 containing full-length
      human wild-type p53 cDNA and vector containing neomycin resistance gene only were
      introduced by lipofectamine-mediated gene transfection into SKOV-3 cell line
      which does not express endogenous p53. The clones obtained were observed for
      their biologic behavior. RESULTS: (1) 2 clones named pC53 and 2 clones named pNeo
      were obtained after pC53-SN3 and vector transfection respectively; (2) The
      morphology of cells either from pC53 or from pNeo did not change significantly
      with respect to their parental SKOV-3; (3) The growth rate of cells from pC53 was
      much slower than that from SKOV-3, while the cell growth curve of pNeo was
      similar to that of SKOV-3; (4) The number of colones formed in the soft-agar by
      pC53 was significantly less than that by SKOV-3 or by pNeo; (5) The percentage of
      phase G1/G0 of pC53 was much higher than that of SKOV-3 and pNeo. CONCLUSION:
      Wild-type p53 cDNA may be considered as one of the target genes for the gene
      therapy of ovarian cancer.

PMID- 9772433
TI  - [Relationship between nm23-H1 expression and lymph node metastasis and prognosis
      in cervical cancer].
AB  - OBJECTIVE: To investigate the expression of nm23-H1 in cervical carcinoma and its
      significance. METHODS: Expression of nm23-H1 was examined by immunohistochemical
      method in 39 cases of adenocarcinoma and 39 cases of squamous cell carcinoma of
      the uterine cervix. The relationship between expression of nm23-H1 and clinic
      pathologic factors and prognosis was analyzed by chi-square test. RESULTS:
      Positive staining rate of nm23-H1 was 44.6% in adenocarcinoma and 39.2% in
      squamous cell Carcinoma. The positive staining rate of nm23-H1 in stage I and II
      adenocarcinoma was 61.1% and 28.6% respectively (P = 0.044); in patients with
      recurrence nm23-H1 positive rate was lower than that in patients without
      recurrence (21.5% vs 56%, P = 0.39); in patients with lymph node negative, nm23
      H1 positive staining was more than that in patients with lymph node positive (52%
      vs 28.6%), however, this difference was not statistically significant (P =
      0.162). None of 14 cases of lymph node metastasis was strong positive stainig,
      whereas 7 of 25 without lymph node metastasis were demonstrated to have strong
      positive staining (P = 0.031). The 5-year survival rate in negative staining
      group was lower than that in the positive staining group (52.5% vs 82.4%, P =
      0.042). In squamous cell carcinoma there was no statistically significant
      relationship between nm23-H1 expression and clinic-pathologic factors and
      prognosis. CONCLUSIONS: nm23-H1 expression was associated with biologic behavior
      in cervical adenocarcinoma.

PMID- 9772434
TI  - [Relationship between human papillomavirus E7 protein and Rb gene product in
      fresh tissues of squamous cervical carcinoma].
AB  - OBJECTIVE: To study the possibility of complex formation of the E7 protein
      encoded by human papillomavirus (HPV) binding to retinoblastoma gene product
      (pRb) in fresh samples of squamous cervical carcinoma (SCC). METHODS: HPV 6/11,
      16, 18, 33 DNA were detected in 40 samples of by polymerase chain reaction
      technique (PCR). The complexes of HPV E7-pRb were examined in fresh tissues of
      HPV contained SCC through capture enzyme linked immunosorbent assay (capture
      ELISA). RESULTS: 45.0% (18/40) of the samples were proved to be HPV positive by
      PCR. Out of 18 samples with HPV positive samples, the complexes of HPV E7-pRb
      were detected in 9 cses, including 1 HPV18 positive and 8 HPV16 positives. The
      complexes of HPV E7-pRb were not found in 2 cases of positive HPV 6/11. No
      correlation was observed between the E7 protein binding to pRb and the
      histological grade of cervical carcinoma (P < 0.05). There was correlation with
      clinical staging, the number of cases showing that the E7 protein pRb complex in
      stage I was significantly higher than that in stages II-IV (P < 0.05).
      CONCLUSIONS: The complex of "high risk" HPV E7-pRb was demonstrated in fresh
      tissues of SCC. There is no correlation between the complex and histological
      grade of SCC. The complex formation may occur in the early developmental stage of
      cervical cancer.

PMID- 9772435
TI  - [Doppler echocardiographic studies on the fetal cardiac function in intrauterine
      growth retardation].
AB  - OBJECTIVE: To assess fetal cardiac function by Doppler echocardiography in
      intrauterine growth retardation (IUGR). METHODS: We investigated the changes in
      cardiac function in 64 normal fetuses and 36 fetuses with IUGR. Blood flow
      velocity waveforms were obtained from the aorta, pulmonary artery and
      atrioventricular valves. The following variables were measured: peak flow
      velocity (PFV), mean velocity (V), accelerate time (ACT), systolic volume (SV)
      and cardiac output (CO) represented the systolic function; the peak early flow
      velocity (PFVe), peak late flow velocity (PFVa), PFVe/PFVa (E/A), mean velocity
      (V) of mitral or tricuspid valve represented the diastolic function. RESULTS: In
      normal fetuses, the PFV, V, ACT of aorta were all greater than those of pulmonary
      artery, whereas SV, CO in left ventricle were smaller. The PFVe, PFVa in mitral
      valve were smaller than those of tricuspid valve. In IUGR fetuses, the PFV, V,
      SV, CO of aorta or pulmonary artery were significantly lower than those of
      normal. The ACT in pulmonary artery decreased significantly, but increased in
      aortic artery. The SV, Co of left ventricle were greater than those of righ
      ventricle. The E/A of mitral and tricuspid valve, PFVe, PFVa, V of tricuspid
      valve were all decreased. The PFVe, PFVa in mitral valve were greater than those
      of tricuspid valve. CONCLUSIONS: The changes of cardiac function in IUGR are
      probably caused by "brain sparing", which means a redistribution of cardiac flow
      after hypoxia.

PMID- 9772436
TI  - [The changes of lipid metabolism and hemorrheology in intrahepatic cholestasis
      during pregnancy].
AB  - OBJECTIVE: To identify the influence of the increased level of serum cholyglycine
      (CG) on lipid metabolism and hemorrheology in patients with intrahepatic
      cholestasis during pregnancy (ICP). METHODS: The concentrations of serum CG,
      total cholesterol (CH), triglycerides (TG), high density lipoprotein-cholesterol
      (HDL-C), low density lipoprotein-cholesterol (LDL-C), high shear and low shear of
      blood specific viscosity (HS and LS), plasma specific viscosity (PV) and
      hematocrit (HCT) were measured in 68 cases of primiparas with single pregnancy
      and 30 healthy nonpregnant women respectively. The group of ICP was composed of
      35 cases with CG > 6 mumol/L, the group of normal pregnancy, 33 cases with CG < 6
      mumol/L. RESULTS: The means of CG and the lipidic parameters in the two pregnant
      groups were significantly higher than those in the non-pregnancy group (P < 0.02
      0.001) except the means of HDL-C between the groups of ICP and non-pregnancy. The
      levels of LDL-C, LDL-C/HDL-C, LS, PV and HCT in the ICP were significantly higher
      than those in the normal pregnancy group (P < 0.02-0.001). CONCLUSIONS: There are
      significant changes of lipid metabolism and hemorrheology in patients with ICP.
      However, these changes could be corrected after pregnancy termination, when the
      level of serum CG returned to normal. The results suggest that the
      pathophysiologic changes of ICP are associated with increased level of serum CG.

PMID- 9772438
TI  - [Human rotavirus infection in perinatal transmission].
AB  - OBJECTIVE: To investigate the perinatal infection of human rotavirus (HRV) in
      pregnant women and the effect on their neonates. METHODS: HRV was examined by RT
      PCR in cervical secretion and feces of 250 pregnant women and fecal samples of
      their neonates on the third postpartum day. RESULTS: In pregnant women the HRV
      prevalence was 26.0% in feces and 8.8% in cervical secration, respectively. The
      infection rate of the 250 neonates in the first three days after birth was 4.4%,
      15.6% and 22.0%, respectively. The HRV infection rate in neonates of infected
      mothers was 52.31%. CONCLUSION: The infected mothers may be an important source
      for HRV infection of neonates. HRV transmitted via the labor tract and
      intrahospital transmission were the main sources for the neonatal infection.

PMID- 9772437
TI  - [Determination of fetal umbilical artery flow velocity during induction of term
      labor by mifepristone].
AB  - OBJECTIVE: To evaluate the effects of mifepristone for induction of term labor on
      blood supply of placenta. METHODS: 97 pregnant women (38-42 gestational weeks)
      were recruited, and randomly allocated into 2 groups, group 1 (n = 49)
      mifepristone was given orally 50 mg q12h for 2 days followed by misoprostol
      intravaginally (25 micrograms q12h); group 2 (n = 48), Sodium prasterone sulfate
      intravenous injection of 200 mg qd for 3 days followed by oxytocin intravenous
      infusion. Fetal umbilical artery flow velocity was determined before and 36-48
      hours after treatment to observe the variation of S/D value in both groups.
      RESULTS: There were no significant variations of S/D value in both groups (P >
      0.05). CONCLUSIONS: Mifipristone for induction of term labor (50 mg q12h for 2
      days) is effective, and has no significant influence on the blood supply of
      placenta.

PMID- 9772440
TI  - [LH-CG receptor protein expression in epithelial ovarian cancer].
AB  - OBJECTIVE: To evaluate the relationship between (LH-CG) receptor expression and
      prognosis in epithelial ovarian cancer. METHODS: The relative quantity of LH-CG
      receptor protein of epithelial ovarian cancer tissuse was detected with
      semiquantitative western immunobloting in 40 cases. The LH-CG receptor protein
      was located with immunohistochemistry. The LH-CG receptor was termed high
      expression if its concentration was more than and/or equal to the median, and low
      expression if its concentration was less than the median. 36 of the 40 cases were
      followed up at various intervals, the longest follow up period was 56 months.
      There were 16 cases with high LH-CG expression and 20 cases with low LH-CG
      receptor expression in which 9 cases died. RESULTS: The positive rate of LH-CG
      receptor protein expression was 72.5% (29/40). The level of LH-CG receptor
      protein expression in patients with stages I and II was higher than that in
      patients with stages III and IV, but it is not significant (P > 0.05). The LH-CG
      receptor concentration in the well-differentiated cancer group was twice as much
      as that in the poorly-differentiated cancer group. The difference between the
      well-differentiated group and the poorly-differentiated group was significant (P
      < 0.05). The 1-year and 3-year survival rates were 83.94% and 67.15% respectively
      in the high LH-CG receptor expression group. Both of the 1-year and 3-year
      survival rates were 33. 34% in the low LH-CG receptor expression group. The
      survival rates of the high expression group was significantly higher than those
      of the low expression group (P < 0.05). LH-CG receptor expression did not
      correlate with age, lymph node metastases, the size of residual tumor and CA125.
      CONCLUSION: The prognosis of patients with high LH-CG receptor expression is
      better than that of those with low expression.

PMID- 9772439
TI  - [Role of nitric oxide in pathogenesis of pregnancy induced hypertension].
AB  - OBJECTIVE: To investigate the role of nitric oxide (NO) in pathogenesis of
      pregnancy induced hypertension (PIH). METHODS: N(G)-nitro-L-arginine-methyl-ester
      (L-NAME) was used to inhibite the synthesizing of NO in the third trimester of
      pregnancy rats. Indices including HGB, PLT, HCT, protein uria, serum endothelin
      (ET), thromboxane B2(TXB2), 6-keto-PGF1 alpha and blood pressure in pregnant rats
      were measured. The length, weight of body, liver and brain of full-term newborn
      rats and the weight and pathological changes of placenta were observed. RESULTS:
      After inhibition of NO synthesis, blood pressure were consistently high. The
      protein uria, HCT, ET, TXB2/6-keto-PGF1 alpha were significantly higher and PLT
      was significantly lower than that of control group. The length, weight of body
      and placenta in neonatal rats were lower than those of the control group (P <
      0.01). Severe ischimic lesion, thrombosis of vessels and endothelial
      proliferation in placenta were observed. CONCLUSION: NO plays an important role
      in pathogenesis of PIH.

PMID- 9772441
TI  - [Estrogen replacement therapy and ovarian cancer].

PMID- 9772442
TI  - [CD44 gene expression and gynecologic neoplasms].

PMID- 9772443
TI  - [Current status of chemotherapy of breast cancer].

PMID- 9772444
TI  - [Promoting the development of critical care medicine in China].

PMID- 9772445
TI  - [Clinical significance of expression of multidrug resistance gene in breast
      cancer tissue].
AB  - OBJECTIVES: To investigate the role of expression of multidrug resistance gene
      (mdr-1 gene) in chemotherapeutic resistance of breast cancer and to determine if
      expression of mdr-1 gene may act as an index for predicting chemotherapy response
      and prognosis. METHODS: Using reverse transcription-polymerase chain reaction (RT
      PCR) technique, we determined the levels of mdr-1 mRNA in 82 breast cancer
      samples. RESULTS: Positive expressions of mdr-1 gene were 34.3% in 35 cases of
      untreated primary breast cancer and 59.0% in 47 cases of relapsed metastatic
      breast cancer, separately, and the difference was statistically significant (P <
      0.05). In 28 cases of relapsed metastatic breast cancer of mdr-1 gene positive
      expression, 22(78.6%) were ever treated with MDR related drugs. Levels of mdr-1
      gene expression of all 7 cases were higher after chemotherapy than before
      chemotherapy. Positive expressions were 16.7% and high grade positive expressions
      were 5.6% in 18 sensitive cases. Positive expressions were 71.4% and high grade
      positive expressions were 50.0% in 14 resistant cases. The difference was
      statistically significant (P < 0.01). There were no relations between expression
      of mdr-1 gene and ages, menopause status, lymphnode involvements, clinical
      stages, and estrogen receptor levels. CONCLUSION: The results indicated that
      retreated metastatic breast cancer is more extensively resistant than untreated
      primary breast cancer and acquired drug resistance is an important reason.
      Expression of mdr-1 gene seems to be a reference index for predicting response of
      chemotherapy.

PMID- 9772447
TI  - [The reversion of multidrug resistance in tumour cell line MCF-7/Adr by
      ribozyme].
AB  - OBJECTIVE: To construct a specific hammerhead ribozyme possessing catalytic
      activity that cleaves the mdr1 mRNA for reversing the resistant phenotype in
      tumour cell line. METHODS: A DNA sequence encoding the ribozyme gene was
      incorporated into a eukaryotic expression vector (pH beta Apr-1 neu) and
      transfected into the human breast carcinoma cell line MCF-7/Adr, which is
      resistant to adriamycin and expresses the MDR phenotype. RESULTS: The ribozyme
      was stably expressed in the cell line, and decreased the level of mdr1 mRNA
      expression by 83.5%. The ribozyme inhibited the formation of P-glycoprotein and
      reduced the cell's resistance to adriamycin. CONCLUSION: The resistant cells were
      1,000-fold more resistant than the parental cell line (MCF-7), whereas those cell
      clones that showed ribozyme expression were only 6-fold more resistant than the
      parental cell line.

PMID- 9772446
TI  - [Clinical research of nipple-areola preserved mastectomy and one-stage breast
      reconstruction with rectus abdominis musculocutaneous flaps].
AB  - OBJECTIVE: To discuss the method for nipple-areola preserved mastectomy with one
      stage breast reconstruction in cancer surgery. METHODS: Because of the merits of
      sufficient blood supply and plasticity of rectus abdominis musculocutaneous flap,
      we used one-stage breast reconstruction after modified radical mastectomy. The
      incision line was covered and the nipple-areola was preserved. The reconstructed
      breast was naturally in contour. RESULTS: 21 cases were treated from 1990 to
      1995, and 18 of them received horizontal-rhombus shaped rectus abdominis
      musculocutaneous flaps and 3 longitudinal-rhombus flaps for breast
      reconstruction. Nipple-areola was preserved in 16 cases. Objective evaluation
      after operation showed that the excellent and satisfied rate reached to 90.5%;
      and subjective evaluation showed that the excellent and satisfied rate reached to
      95.2%. Thirteen cases have been followed up for 3 years, and 9 for 5 years. Three
      year survival rate was 100% (13/13), and 5-year 88.9% (8/9). CONCLUSION: The
      method is recommendable for the treatment of stage I-II breast cancer.

PMID- 9772448
TI  - [Mulivariate analysis of prognostic factors in non-small cell lung cancer].
AB  - OBJECTIVES: To find independent prognostic factor of non-small cell lung cancer
      (NSCLC), identify the population with "high-risk" of recurrence and death in
      resected NSCLC, and direct adjuvant therapy for clinical doctors. METHODS: 85
      resected patients from NSCLC were followed up. All patients were subjected to the
      study by light microscope, immunochemistry, PCR-SSCP method, and DNA image
      analysis. Thirteen clinical, pathological, and biological factors were analysed
      by Cox regression model. RESULTS: The median follow-up period was 47 months. The
      overall 3-year survival rate was 66% and the overall 5-year survival rate 61%.
      Cox regression showed significant univariate predictors (P < 0.05) of early
      recurrence and death for NSCLC were lymphnode status, pTNM, tumor emboli,
      microvessel count, Ki-67 antigen labeling, DNA relative content and p53 gene
      mutation. Microvessel count (P < 0.001) and pTNM (P = 0.006) were independent
      predictors of early recurrence and cancer-death. According to the multivariate
      model for predicting early recurrence and cancer death, prognostic index (PI) was
      calculated. CONCLUSION: The PI may be a useful clinical tool for evaluating
      prognosis of patients and identifying the population with "high-risk" of
      recurrence and death in NSCLC.

PMID- 9772449
TI  - [The relations between mutations of p53 anti-oncogene in atherosclerosis and
      levels of lipids in serum].
AB  - OBJECTIVE: To further understanding the pathogenesis of human atherosclerosis, we
      studied the mutations of p53 anti-oncogene in Chinese atherosclerosis lesions and
      the relations between p53 gene mutations with the levels of serum lipoprotein and
      the contents of lipids in AS tissues. METHODS: p53 gene mutations were detected
      by a-32P-dCTP labelled radiative PCR-SSCP and the biochemical analyses of lipids
      in serum and AS tissues. RESULTS: In 89 cases studied, 9 were found the p53 gene
      multi-hotsports exons mutations. The TC, TG and CE contents in vascular AS
      tissues in p53 gene mutation group were higher than those in non-mutations group
      (ANOV: F = 4.56-9.97, P < 0.05-0.01, no differences in PL contents). But there
      were no statistic differences in serum levels of TC, TG, CE and apoAI between the
      two groups (P > 0.05-0.25). All the levels of the serum lipoproteins studied were
      almost in normal ranges. CONCLUSION: The DNA structural mutations of p53 anti
      oncogene in Chinese adults' AS tissues have remarkable relations with the
      severity of AS lesions. The mutations of p53 gene may play some important roles
      in the formation of human atherosclerosis. In addition to serum lipid disorders,
      this may be a new mechanism in the pathogenesis of human atherosclerosis.

PMID- 9772450
TI  - [Protective effect of magnesium on ionic channels in guinea pig ventricular
      myocytes during hypoxia].
AB  - OBJECTIVE: To determine effects of Mg2+ on potassium current, transient inward
      current (Iti) and Na(+)-Ca2+ exchange current in isolated ventricular myocytes
      during hypoxia. METHODS: Single myocytes were isolated from ventricles of adult
      guinea pig hearts. The patch clamp technique in whole cell configuration was used
      to study ionic currents, and experiments were performed in an experimental
      chamber that allows the cell to be exposed to a sufficiently low O2 pressure.
      RESULTS: The 10 mmol/L intracellular free Mg2+ (Mg2+i) had no effect on action
      potential abbreviation under normoxic condition, however, the action potential
      abbreviation during hypoxia was markedly inhibited in presence of 10 mmol/L
      Mg2+i. The amplitude of hypoxia-induced time independent outward K+ current was
      also greatly reduced when applied 10 mmol/L Mg2+ in pipette solution. In early
      reoxygenation, Iti occurred in 73% of myocytes, 10 mmol/L extracellular Mg2+
      during hypoxia and reoxygenation lowered incidence of Iti, 10 mmol/L Mg2+ could
      partly inhibit the Na(+)-Ca2+ exchange current in normoxic condition. CONCLUSION:
      Intracellular Mg2+ could block hypoxia-induced outward current through ATP
      sensitive potassium channels. Mg2+i plays an important role in preventing
      depletion of cellular K+ and regulates beat-to-beat cardiac activity.
      Extracellular Mg2+ most probably decreases the signs of calcium overload in early
      reoxygenation by inhibiting Na(+)-Ca2+ exchange.

PMID- 9772451
TI  - [Double effects of arsenic trioxide (As2O3) on acute promyelocytic leukemic cell
      line].
AB  - OBJECTIVE: To investigate the effects of a wide range of concentrations of As2O3
      on NB4 cells. METHODS: Cell morphology, cell-DNA content distribution, CD11b and
      CD33 antigens and nitroblue tetrazolium (NBT) reductions were evaluated in an APL
      cell line NB4 cells with or without As2O3 treatment. In addition,
      immunofluorescent analysis for APL marker molecule PML-RAR alpha was also
      performed. RESULTS: 1-2 mumol/L of As2O3 treated NB4 cells presented
      morphologically some features of apoptotic cells such as intact cell membrane,
      chromatin condensation and nuclear fragmentation. Sub-G1 cells, whose percentage
      presents concentration and time-dependency, were observed by flow cytometer.
      Otherwise, NB4 cells with the treatment of As2O3 at 0.1-0.25 mumol/L for a long
      time (10 days) have differentiation-related morphology, and their differentiation
      antigens CD11b and CD33 were also modulated to some extent. In addition, 0.1-2
      mumol/L of As2O3 could rapidly and effectively modulate and degradate PML/PML-RAR
      alpha proteins. CONCLUSION: As2O3 had double effects (induction of apoptosis and
      imcomplete differentiation) on NB4 cells, which could associate with rapid
      modulation and degradation of PML/PML-RAR alpha proteins.

PMID- 9772453
TI  - [Changes of BDNF mRNA by molecular hybridization during embryonic spinal cord
      repairing injury of adult rats].
AB  - OBJECTIVE: To study the changes of (brain-derived neurotrophic factor) BDNF mRNA
      during embroyonic spinal cord repairing spinal cord injury of adult rats.
      METHODS: At day 1,3, 5, 7, 10, 15, and 30 after embryonic spinal cord being
      transplanted into acutely injured spinal cord of adult rats, changes of BDNF mRNA
      within donor tissue and host tissue were demonstrated qualitatively and
      quantitatively by in situ hybridization and dot hybridization. RESULTS:
      Qualitatively, BDNF mRNA was mainly expressed within cytoplasm of motor neurons
      and a few gliocytes in normal spinal cord. After spinal cord injury, hybridizing
      products expanded to the mediate and small-sized neurons, also more gliocytes
      took part in hybridization response. Following transplantation, positively
      hybridizing neurons and gliocytes increased in number in host tissue, and
      embryonic spinal cord kept an expressing level similar to that before being
      transplanted. It was also revealed quantitatively that reacting intensity of the
      cells in the injured group was strikingly higher than that in the normal group.
      However, hybridization intensity in the transplanted group was even higher at
      many intervals than that in the injured group. Besides, the lasting period for
      hybridization reaction in the transplanted group was also different from that in
      the injured group. The most intensive reacting phase in the former presented at
      day 10 and 15, and in the latter at day 7 after operation. CONCLUSIONS: We
      suggest that transplanted embryonic spinal cord can, besides provision neurol
      trophines for itself and host spinal cord, evoke synthetic mechanisms of host
      spinal cord once holding during its embryonic development so as to enhance
      expression of the neurotrophin. In this way, the host spinal cord may provide
      neurotrophin for its regeneration and provide an trophic environment for the
      grafts to develop and differentiate.

PMID- 9772452
TI  - [Synthesis and degradation of type IV collagen in rat experimental liver
      fibrosis].
AB  - OBJECTIVE: To investigate the synthesis and degradation of type IV collagen in
      CCl4-induced SD rat liver fibrosis. METHODS: Dynamic changes and relationships
      among the tissue alpha 1 (IV) procollagen mRNA, type IV collagen (Col IV) and
      serum 7S polypeptide fragment of Col IV in fibrotic livers induced by CCl4 with
      choline difficiency diet were studied using immunohistochemistry, Northern
      analysis, in situ hybridization and serum RIA techniques. RESULTS: The
      transcription of alpha 1 (IV) procollagen mRNA in fibrotic liver and the content
      of serum 7S polypeptide fragment derived from tissue Col IV degradation was
      enhanced promptly and obviously in earlier stage of experiment, but not
      synchronous afterwards. In the early stage of experiment, alpha 1 (IV)
      procollagen mRNA transcripts was localized in sinusoid Ito cells and endothelial
      cells. In the mid and late stage, alpha 1 (IV) procollagen mRNA transcripts was
      localized in myofibroblasts (MFs), fibroblasts (Fbs) and endothelia of small
      blood vessels in fibrotic septa. CONCLUSIONS: The change of serum 7S polypeptide
      fragment could reflect the motabolic state of Col IV and the degree of tissue
      injury in fibrogenesis and might have some clinical significance in identifying
      the activiation of the liver fibrosis. The "Ito cell-myofibroblast-fibroblast"
      effective cell system and sinusoid endothelia were the Col IV producing cells
      during fibrogenesis, in which sinusoid endothelia, as another source of Col IV
      production, participated in the capillization of liver sinusoids.

PMID- 9772454
TI  - [Clinical diagnostic valuation cine magnetic resonance coronary angiography].
AB  - OBJECTIVE: To assess the ability of imaging coronary arteries noninvasively with
      magnetic resonance angiography technique (MRCA) and its diagnostic value in
      coronary artery disease. METHODS: MRCA was performed on 33 subjects, including 12
      healthy adult volunteers and 21 patients with available recent X-ray contrast
      angiography (XCA) results. MRCA technique consisted of a gradient echo sequence
      (Turbo-Cine), two-dimensional acquisition, fat suppression, peripheral gating.
      Subjects were imaged in supine position using a standard body coil, without
      breath-hold. RESULTS: All 33 subjects were imaged successfully. Identification of
      the coronary artery was possible for the right coronary, left main stem, left
      anterior, and left circumflex arteries respectively in 97%, 100%, 91% and 91%
      with a visualized mean length of 51 +/- 15 (28-80 mm), 11 +/- 4 (4-22 mm), 44 +/-
      13 (24-66 mm), 40 +/- 12 (20-66 mm). In the 21 subjects with available XCA
      results, 78% (29/37) proximal stenoses of the coronary arteries were detected
      with MRCA. CONCLUSION: At current stage, MRCA can depict most of the
      hemodynamically significant proximal stenoses but not the distals. This procedure
      can be used as an alternative imaging application under certain clinical
      indications.

PMID- 9772455
TI  - [Gene transfer in skeletal muscle cell and gene therapy].

PMID- 9772456
TI  - [Selection of diagnostic indexes in the diagnosis of virus hepatitis].

PMID- 9772457
TI  - [Research on the variation of hepatitis B virus and problems in the evaluation of
      its clinical significance].

PMID- 9772458
TI  - [Inhibition of hepatitis C virus by antisense oligodeoxynucleotide in vitro].
AB  - OBJECTIVE: To study inhibitory effect of antisense oligodeoxynucleotide (asODN)
      on HCV in vitro. METHODS: The H9 cells transfected by pCD-HCV, a recombinant HCV
      containing total HCV structural gene, were treated with two 15-mers
      phosphorothioate (PS) ODNs complementary (PS-ASON) and homologous (PS-ODN) to HCV
      core genomic region, which were labeled with digoxin (DIG). Spot blot
      hybridization was carried out. Treated by the two ODNs, rPS-ODN (a 15-mers PS ODN
      of random sequence) or PS-ASON were modified with two liposomes (DOTAP and
      Lipofectin) and calcium phosphate precipitation respectively. With a half-ration,
      the variation of level of HCV mRNA and HCV antigen expression was observed by RT
      PCR and dot ELISA. 3H-TdR adding test was done to observe PS-ASON cytotoxicity.
      RESULTS: PS-ODN and PS-ASON were detected in the H9 cells. The target gene was
      hybridized to PS-ASON and PS-ODN labeled with DIG. PS-ASON cut down level of HCV
      mRNA and HCV antigen expression obviously. However, PS-ODN and rPS-ODN did not
      influence the level of the both. The time-dependent and dose-dependent inhibition
      of PS-ASON was observed. In contrast to free PS-ASON, both of liposomal PS-ASON
      showed more highly effective inhibition, but calcium phosphate precipitation-PS
      ASON complex did not. The results showed PS-ASON did not influence the H9 cells
      growth at 10 mumol/L. CONCLUSION: PS-ASON complementary to HCV core gene is asODN
      and exerts antisense-inhibitory effect on the level of HCV translation obviously,
      but not on the level of HCV replication and transcription.

PMID- 9772459
TI  - [Mutations and their significance in the corepromoter region of hepatitis B
      virus].
AB  - OBJECTIVE: To study the mutations in the core promoter (CP) region of hepatitis B
      virus (HBV) in Chinese viral hepatits B patients. METHODS: CP regions of 48 HBV
      strains were analysed by polymerase chain reaction (PCR) direct sequencing
      approach. RESULTS: 67% of the samples were detected to have point mutations in
      the CP region. The hot spots located in nt 1754-1766 and nt 1801-1811 while
      nucleotides in nt 1777-1800 and nt 1812-1836 were highly conserved. nt. 1764
      mutation was present in HBeAg negative patients. There were 16 point mutations in
      region overlapping X gene, 9 of which lead to amino acid change. CONCLUSION:
      Though mutations in CP region of HBV appear frequently, the sequences associated
      with viral transcription are rarely changed. Point mutation at nt 1764 is related
      to HBeAg negative phenotype, but it is not the specific mutation of fulminant
      hepatitis. The importance of mutations in the X gene overlapping region needs to
      be further investigated.

PMID- 9772460
TI  - [Molecular diagnosis of beta-thalassemia intermedia].
AB  - OBJECTIVES: To analyze the molecular abnormalities of beta-thalassemia intermedia
      and contribute to the knowledge of the molecular diagnosis and prenatal diagnosis
      of this disorder. METHODS: In 14 patients with beta-thalassemia intermedia, we
      analyzed the hematologies, alpha, beta and gamma globin gene organization and
      structure as well as globin gene biosynthesis by Southern blot hybridization,
      multiplex allale specific PCR (MAS-PCR), DNA sequencing and micro-globin chain
      biosynthetic assay. Moreover, alpha globin gene organization was studied in 250
      cord blood specimens. RESULTS: Of the 14 patients, 4 were found to be beta
      thalassemia heterozygotes combined with rightward cross-over or/and leftward
      cross-over triplicated haplotype of alpha-globin gene loci (alpha alpha alpha
      anti3.7 or/and alpha alpha alpha anti4.2), 3 were compound heterozygotes for beta
      thalassemia combined with alpha-thalassemia 1 or 2, one was identified to be a
      compound heterozygote for beta-thalassemia combined with G gamma promotor-158 (C-
      >T) mutation. The data of the alpha globin gene organization in 250 cord blood
      specimens showed that 8 of the 500 tested chromosomes (1.6%) were abnormal: 3
      were alpha alpha alpha anti3.7, 4 were alpha -3.7, and one was --SEA. CONCLUSION:
      In addition to beta-thalassemia homozygote or compound heterozygotes with alpha
      thalassemia, the conjunctive abnormalities of beta-thalassemia heterozygote with
      alpha-globin gene triplication was another major cause of beta-thalassemia
      intermedia.

PMID- 9772461
TI  - [3-D morphological study of the temporal bone].
AB  - OBJECTIVE: To establish the 3-D(three-dimensional) morphological study of the
      temporal bone by means of computer graphic techniques. METHODS: The serial
      sections of the temporal bone were processed by the technique of computer-aided 3
      D reconstruction. The 3-D images of the multi-structures in the temporal bone
      were displayed on the monitor. The 3-D parameters of these structures were
      measured by a special software. The stereo-images of the structures in the
      temporal bone were obtained by stereoscopy and stereo-pairs. RESULTS: Most
      structures of the temporal bone were reconstructed in 37 instances for the
      different purpose of study. Each set of the stereo-pair corresponding to the
      structures in the temporal bones and many 3-D parameters were obtained. The
      complex spatial relationship among the reconstructed structures such as the
      facial nerve, endolymphatic sac, posterior tympanum and posterior ampullary nerve
      was revealed and the mechanic model of the ossicular chain was set up. According
      to these results, the surgical approach of the posterior ampullary nerve
      transection was designed and simulated on the graphic computer. CONCLUSION: The
      technique of computer-aided 3-D reconstruction provides a new tool for the study
      of the temporal bone. It is also helpful for the designs and simulations of the
      surgical approaches. The results of this study contribute to developmout of a new
      branch of pathology of the temporal bone and a primary 3-D morphological study of
      the temporal bone.

PMID- 9772462
TI  - [Blood pressure responses to cold pressor stress and its relation to sodium
      metabolism in salt-sensitive children].
AB  - OBJECTIVE: To investigate the blood pressure responses to cold pressor stress and
      its relation to sodium metabolism in salt-sensitive children. METHOD: 268
      children aged 10.6 +/- 1.1 years were detected salt-sensitivity with the tests of
      oral saline load and furosemde sodium-volume depletion. Cold pressor stress test,
      sodium metabolism, and the related factors were measured. RESULTS: 25% of the
      children were detected to be salt-sensitive. The increased extent of blood
      pressure and its recovery time from peak to baseline in salt-sensitive children
      were significantly higher than those in non-salt-sensitive children during the
      cold pressor stress test (t = 5.14, 3.94, P < 0.01 and t = 2.16, P < 0.05). The
      increased extent of blood pressure and its recovery time during cold pressor test
      were correlated positively with red-cell sodium content, and were correlated
      negatively with 2 hour urinary sodium excreation during the oral saline load
      test. CONCLUSION: Children with salt-sensitivity have a remarkably increased
      blood pressure responses to cold pressor stress (sympathetic activity), which is
      related with abnormal sodium metabolism.

PMID- 9772463
TI  - [Clinical and experiment study of cooling therapy on burned wound].
AB  - OBJECTIVE: To observe the subjective benefit of pain relief by cooling therapy
      when wound temperature drops to below 28 degrees C (threshold for pain). METHOD:
      22 patients with partial-thickness burns who received cooling therapy showed 2
      days early healing as compared with untreated burn wounds. As a first aid
      measure, prolonged cooling therapy (up to 30') was recommended. In experimental
      study, the protective effects with cooling therapy were observed in wistar rats
      with deep second degree burns. RESULTS: Lower epithelial cell activity and higher
      schiff alkaline values were seen in the wound skin tissue in the non cooling
      therapy than in early cooling therapy groups and healthy controls. The groups
      with early cooling therapy (at once, 10', 20' after scalded injuries) the
      epithelial cell activity maintained at 83%, 80%, 65%. CONCLUSION: The results
      suggest that cooling therapy can protect the epithelial cell activity to some
      extent after scalded injuries which may be associated with inhibition of lipid
      peroxide.

PMID- 9772464
TI  - [Clinical significance of HCG in both maternal serum and placental tissue in
      normal term women and patients with pregnancy induced hypertension].
AB  - OBJECTIVE: To determine the maternal serum level of HCG beta and the hormones in
      normal term women and patients with pregnancy induced hypertension. METHOD:
      Semiquantitative immunohistochemistry of placental tissue was used in 193 normal
      term women and patients with pregnancy-induced hypertension (PIH). RESULTS: A
      strongly positive correlation between the maternal serum level of HCG and the
      immunostained positive syncytiotrophoblasts (ST) was found (correlated
      coefficient: 0.65, P < 0.01). Maternal serum HCG was produced mainly from
      placental ST. Serum HCG beta and HCG positive cells of the placenta were
      obviously higher in patients with PIH than those in normal term women (P < 0.01).
      An increase of HCG level was noted in maternal serum and the placental tissue
      with PIH. CONCLUSION: Abnormal higher HCG level may affect the pathogenesis of
      PIH.

PMID- 9772465
TI  - [Influence of experimental fluorosis on phospholipid content and fatty acid
      composition in rat brain].
AB  - OBJECTIVE: To investigate the pathogenesis of brain damage by fluoride
      intoxication, phospholipid content, and fatty acid composition in rat brain with
      fluorosis were annlysed. METHODS: Wistar rats were fed with NaF in various
      amounts and time periods to produce the animal model with chronic fluorosis.
      Phospholipid content and fatty acids composition were analysed using high
      performance liquid chromatography and gas chromatography, respectively. RESULTS:
      All animals fed with high amount of fluoride suffered from chronic fluorosis. The
      total brain phospholipid content was lower in the rat treated with fluoride,
      which mainly influenced phosphatidylethanolamine, phosphatidylcholin, and
      phosphatidylserine. No modifications were detected in fatty acid and aldehyde
      compositions of individual phospholipid classes. CONCLUSION: The metabolism of
      brain phospholipid might be interfered by fluoride accumulated in brain tissue,
      which is related with the degeneration of neuron. The changes of brain
      phospholipid could be involved in the pathogenesis of chronic fluorosis.

PMID- 9772466
TI  - [Expression of nm23/NDPK, integrin, type IV collagenase and uPA in transplanted
      tumors with various metastatic potential in nude mice and surgical specimens].
AB  - OBJECTIVES: To observe the relationship between the metastasis of human lung
      carcinoma and the expressions of nm23/NDPK, integrins, type IV collagenase and
      uPA. METHODS: By ABC immunohistochemical staining, we observed the expressions of
      nm23/NDPK, integrins, type IV collagenase and uPA in four strains of subcutaneous
      transplanted tumors and 87 surgical specimens for human lung carcinoma. The
      metastatic potential of four xenografts varied from low to high among PLA-801C,
      Anip973, PLA-801D, PLA-801DL. The effects of beta 1 antibody and the RGD peptide
      on the PLA-801DL xenograft were studied in the nude mice. RESULTS: High
      expression of nm23/NDPK was observed in the four xenografts and specimens from
      the 87 patients. No association was found between expression of nm23/NDPK and
      lymph node metastasis. Low expressions of beta 1 subfamily integrins were
      observed in the four xenografts. beta 1 subunit antibody and RGD peptide had no
      effect on metastasis of PLA-801DL xenograft. The expressions of type IV
      collagenase were positively correlated with their metastatic capacity in the four
      xenografts and surgical specimens from the 87 patients. Anip973 and PLA-801D
      showed positive staining to uPA, while PLA-801DL and PLA-801C were negative.
      CONCLUSIONS: The expression of type IV collagenase is positively correlated with
      the metastatic capacity of lung carcinoma. Although high expression of nm23/NDPK,
      low expression of integrins, and various expression of uPA were observed, these
      were not correlated with metastatic capacity of lung carcinoma.

PMID- 9772467
TI  - [Oxygen free radical on interleukin-1 activity of hemorrhage/resuscitation rat].
AB  - OBJECTIVE: To investigate the effects of oxygen free radical on the enhancement
      of IL-1 activity in vivo and in vitro on hemorrhagic and resuscitated rat.
      METHODS: 30% of rats total blood volume was withdraw by carotid artery catheter
      and resuscitated with 2 times of lost blood volume 1 h later. RESULTS: Plasm IL-1
      activity and MDA content increased and SOD activity decreased significantly 1-4
      hours after resuscitation. There was a marked correlation between IL-1 activity
      and MDA content as well as SOD activity. Treatment with SOD as resuscitation
      prevented the postresuscitation increase in plasma IL-1 activity significantly.
      Hemorrhage and resuscitation also caused significant decrease of SOD activity and
      elevation of MDA in peritoneal macrophage 2 hours after resuscitation. After
      preincubation with SOD for 1 hour, the macrophage presented a much lowered
      capacity to release IL-1. CONCLUSION: Oxygen free radical may be one of the most
      important factors that contribute to elevation of IL-1 level after hemorrhage and
      resucitation.

PMID- 9772469
TI  - [Improvement of surgical standards and diagnosis of hepatic bile duct calculus in
      China].

PMID- 9772468
TI  - [An experimental study of the endothelin-1 change in rat kidney after severe
      burn].
AB  - OBJECTIVE: To observe the changes of endothelin-1 (ET-1) concentration,
      immunohistochemical distribution, mRNA expression and localization in kidney of
      severe burn rat. METHODS: Wistar rats sustained with 30% TBSA III degree burn
      were divided randomly into 6 groups: normal control, 1, 3, 6, 12, and 24 postburn
      hour (PBH). The items studied were: the level of ET-1 in renal vein plasma and
      kidney tissue (cortex, outer medulla and inter medulla respectively),
      immunocytochemical distribution of ET-1 in kidney tissue by light and electron
      microscopy, mRNA expression of ET-1 in kidney by northern blot hybridization,
      localization and enumeration of mRNA expressiong cells of ET-1 by in situ
      hybridization. RESULTS: The rat kidney secretion and mRNA expression of ET-1 more
      evidently increased at 1, 3 PBH respectively than in normal control (P < 0.01),
      They distributed primarily on endothelial cells, glomerular mesangial cells.
      Tubular epithelial cells reached maximal mRNA expression and immunoreactivity at
      3, 6 PBH respectively. Immune electron microscopic study demonstrated that ET-1
      (gold particles) localized on the intracellular lumen surface of endothelium but
      on both apical and basal surfaces of epithelium. CONCLUSION: Secretion and mRNA
      expression of ET-1 increased obviously in kidney in early stage after severe
      burn.

PMID- 9772470
TI  - [Clinical studies of surgical methods for lobar and segmental bile ducts of the
      right liver].
AB  - OBJECTIVE: To Study the operative approach and the method of exposure and cutting
      open for every lobar and segmental bile ducts and solve the surgical treatment of
      the complex multiple stones complicated with bile ducts stenosis in the right
      liver. METHODS: Liver specimens of 30 adults were dissected to explore the lobar
      and segmental bile ducts and vessels. The exposure and cutting open of right
      intrahepatic bile ducts were well from the diaphragmatic face of the right
      hepatic lobe. This method was used in 10 patients with the disease. RESULTS: All
      the patients were succesfully treated. Follow-up for 3-36 months, showed that 80%
      patients had excelent results, and 20% good ones. CONCLUSION: The exposure and
      cutting open of the intrahepatic bile ducts from the diaphragmatic face of the
      right liver may take stones and solve bile duct stenosis in the every lobes and
      segment of the right liver.

PMID- 9772471
TI  - [Resection of primary liver cancer following transcatheter arterial
      chemoembolization: clinicopathological features and postoperative course in
      cases].
AB  - OBJECTIVE: To study the clinicopathological changes and post-operative course
      following transcatheter hepatic arterial chemo-embolization (TACE) in primary
      liver cancer (PLC). METHODS: One hundred and eighty-two cases of PLC were
      resected in 8 years. 35 cases of them that resected after 1-5 times of TACE were
      evaluated. 11 of the 35 cases were 5 cm or less in diameter, 24 cases were larger
      than 5 cm. RESULTS: Uptake of iodized oil, shrinkage of tumor mass and decrease
      of AFP level were good clinical features of the tumor after TACE and were related
      to the times of TACE. Only 7 of the 35 cases after TACE with 100% necrosis were
      found pathologically. The degree of necrosis was relative to injured vessels of
      PLC and was also related to the times of TACE. Post-operative survival rate and
      disease-free survival rate of the 35 cases in 5 years were 40.5% and 28.9%,
      respectively. CONCLUSION: Single treatment of TACE is not curative to PLC, and it
      is essential to seize a chance to perform secondary liver resection of
      unresectable PLC after 2-3 times of TACE.

PMID- 9772472
TI  - [The expression of calponin in Oddi's sphincters and its actions during gallstone
      formation].
AB  - OBJECTIVES: To study on the expression of calponin in an animal model of
      gallstone disease and investigate the molecular mechanisms of gallstone
      formation. METHODS: After feeding a high-cholesterol diet to guinea pigs, Oddi's
      sphincters were disseced on day 30 and day 60 respectively. We used RT-PCR,
      western-blotting to evaluate expression level of calponin gene. RESULTS: Down
      regulation of calponin gene expression was observed in animals with gallstone.
      The levels of both protein and mRNA expression for calponin on day 30 and day 60
      were lower than those of control group with the level from day 60 lower than that
      from day 60, while myosin expressions were relatively stable. CONCLUSION: Our
      results indicated that the decrease of calponin could increase the pressure of
      sphincter of Oddi, aggravate the stasis of bile and promote the gallstone
      formation.

PMID- 9772473
TI  - [Repair of the splicing defect of thalassemic allele beta IVS-2-654 C-->T in
      cultured human erythroid cells by antisense RNA].
AB  - OBJECTIVE: To investigate the repair of the splicing defect of thalassemic allele
      beta IVS-2-654 C-->T (beta 654) in cultured human adult erythroid cells (hAE) by
      antisense RNA A2. METHODS: Vectors expressing antisense RNA fragments A2 which
      targeted against the aberrant splice sites of beta 654 pre-mRNA were introduced
      into hAE by lipid-mediated DNA-transfection method. Quantitation of beta-globin
      mRNA by RT-PCR and micro-biosynthesis of globin chain assay were used to measure
      the expression of globin genes in hAE from day 0 to day 8 after transfection.
      Meanwhile, hAE transfected with random antisense sequence was used as control.
      RESULTS: Antisense RNA A2 treatment restored the correct splicing of beta 654 pre
      mRNA. The proportions of correctly spliced beta-globin mRNA (beta/beta + beta*)
      increased from 0.024 (before transfection) to 0.380 (8th day after transfection)
      in hAE obtained from individual with beta 654/ beta 41-42 mutations and, from
      0.396 to 0.883 in hAE obtained from individual with beta 654/beta A genotype.
      Correspondently, microglobin biosynthesis of chain revealed that the ratio of
      beta/alpha increased from 0.052 to 0.359 in the former and, from 0.624 to 0.820
      in the later case, respectively. There was no difference with or without
      antisense RNA A2 treatment on hAE obtained from normal controls. CONCLUSIONS:
      Antisense RNA A2 treatment could restore efficiently the correct splicing of beta
      654 pre-mRNA and, consequently improve the imbalance of globin chains in
      thalassemic cells. This method is of potential clinical interest in gene therapy
      of the disease.

PMID- 9772474
TI  - [SCA1, SCA2, MJD/SCA3 (CAG)n mutation detection and analysis in patients with
      hereditary spinocerebellar ataxia from Chinese families].
AB  - OBJECTIVE: To assess the frequency of the SCA1, SCA2, MJD/SCA3 CAG trinucleotide
      repeat expansions ((CAG)n) among individuals diagnosed with hereditary
      spinocerebellar ataxia (SCA) from Chinese families. METHOD: The SCA1, SCA2,
      MJD/SCA3 (CAG)n mutation were detected with the polymerose chain reaction (PCR),
      denaturing polyacrylamide gel and silver staining technique in 79 patients with
      autosomal dominant SCA from 50 Chinese families. RESULTS: Among 50 kindreds, 2%
      (1/50) had the SCA1, (CAG)n, 6% (3/50) had the SCA2, (CAG)n, whereas 48% (24/50)
      were positive for the MJD/SCA3 (CAG)n. Thus, together SCA1, SCA2, and MJD/SCA3
      represent 56% (28/50) of the autosomal dominant ataxias in our group. In two SCA1
      patients the CAG repeat was expanded to 53-62 repeats, whereas in normal
      ivdividuals was 12-36 repeats. In seven SCA2 patients the CAG repeat was expanded
      to 43-47 repeats, whereas in normal ivdividuals was 22-30 repeats. In forty-two
      MJD/SCA3 patients the CAG repeat was expanded to 63-78 repeats, whereas in normal
      ivdividuals was 15-38 repeats. The SCA1, SCA2, MJD/SCA3 (CAG)n mutation were
      excluded in the other 28 SCA patients from 22 families. CONCLUSION: The frequency
      of MJD/SCA3 is substantially higher than that of SCA1 and SCA2 in the autosomal
      dominant SCA from Chinese families. Chinese patients with MJD/SCA3 are non
      Portuguese patients with MJD/SCA3. Clinical expressions of the various SCAs
      overlap one another, making a diagnostic classification based on phenotype
      inaccurate in many instances. It is important for SCA clinical study to make a
      SCA gene diagnosis and genomic classification.

PMID- 9772475
TI  - [Cloning and expression of a novel gene related to hypertension].
AB  - OBJECTIVE: To search and clone novel genes related to hypertension. METHODS:
      Using differential display, a RNA mapping method, we identified differentially
      expressed RNAs from cultured VSMCs of WKY and SHR. Down-expressed cDNAs of WKY
      were cloned. RESULTS: A novel cDNA (rHRG-1) obtained contained 4,160 bp
      nucleotides and an open reading frame which encoded 551 amino acid residues. Its
      molecular weight was 62,644. Northern blot analysis showed that the mRNA was
      expressed not only in VSMCs but in various rat tissues (heart, liver, brain, lung
      and kidney). Besides, the expression of rHRG-1 mRNA in various tissues (heart,
      liver, brain and kidney) of WKY rat was higher than that in those tissues of SHR.
      Semi-quantitative RT-PCR analysis showed that the expression of rHRG-1 mRNA was
      down-regulated by treating cells with angiotensin-II, endothelin-I or interleukin
      I. VSMCs proliferation and hypertension-stimulating factor, but was up-regulated
      when treating cells with ANF, CGRP or adrenomedullin which could inhibit the
      proliferation of VSMCs and attenuate hypertension. These effects could be blocked
      or attenuated by corresponding antagonists or antibodies. CONCLUSION: The
      isolated novel rat cDNA (rHRG-1) is related to VSMCs proliferation or
      hypertension. It may antagonize the proliferation of VSMCs and may be involved in
      the formation of hypertension.

PMID- 9772476
TI  - [Suppression of metastatic phenotype of cloned mouse lung adenocarcinoma cells by
      transfer of human genomic DNA].
AB  - OBJECTIVE: To isolate and identify human sequences with metastatic suppression
      ability. METHODS: Genomic DNA fragments isolated from normal human lung tissue
      were transfected into cloned highly metastatic mouse lung adenocarcinoma cells
      together with PSV2neo as selectable marker. RESULTS: 25 transfectants were cloned
      in medium containing G418 and Ouabain. Eight morphologically flat revertants
      exhibited a more normal phenotype, six clones containing human DNA were
      identified by a sensitive Inter Alu-PCR method. The rate of cell growth and
      colony formation in agar were detected in vitro. Clone 12, 20 and 32 showed a
      lower ratio than maternal untransfected cells. In vivo clone 12 showed more
      significent less spontaneous metastases in nude mice and syngeneic T739 mouse
      than control group. CONCLUSION: The results indicated that the inserted human DNA
      may be responsible for suppression of metastatic phenotype of mouse lung
      adenocarcinoma cells.

PMID- 9772477
TI  - [Transfection and expression of human thrombopoietin cDNA for treatment of
      thrombocytopenia in mice].
AB  - OBJECTIVES: To explore that COS-7 cells efficiently transfected with human
      thrombopoietin (hTPO) cDNA from fetal liver and hTPO potentially treated
      carboplatin-induced thrombocytopenia in mice. METHODS: Using molecular cloning
      technique, expression vectors PCIneo under the control of SV40 early. Applying
      liprofectin mediating method, recombinant plasmids PCIneo-hTPO were transfected
      into COS-7 cells in addition to effect of G418. After hTPO cDNA and mRNA in
      colony COS-7 cells were respectively identified by PCR-Southern and dot blot,
      hTPO was analysed with sandwich ELISA and administrated intraperitoneally to mice
      with thrombocytopenia. RESULTS: COS-7 cells transfected with constructed PCIneo
      hTPO expressed and secreted hTPO up to 48.28 ng/ml in the supernatant. We
      kinetically observed that the number of megakaryocyte-colony-forming unit (CFU
      MK) in bone marrow enhanced to threefold (P < 0.01), especially the number of
      small CFU-MK, accompanied by an increased mean megakaryocyte volume (P < 0.01)
      and circulating platelets returned to a normal level (80 +/- 26, x 10(9)/L, P <
      0.01) in peripheral blood. CONCLUSION: Recombinant PCIneo-hTPO can efficiently be
      transfected into COS-7 cells and hTPO is an effective cytokine for treating
      carboplatin-induced thrombocytopenia in mice.

PMID- 9772478
TI  - [The new parameters of motor unit potential in the diagnosis of neurogenic
      lesions in spike-triggered averaging electromyography].
AB  - OBJECTIVE: To evaluate the clinical significance of the new parameters of motor
      unit potential (MUP) to the diagnosis of neurogenic lesions. METHODS: Three
      groups of muscles, anterior tibialis, abductor pollicis brevis and vastus
      medialis were studied with spike-triggered averaging electromyography (EMG). A
      total of 3,646 MUPs, 1,903 from normal group and 1,743 from neurogenic group,
      were recorded under slight muscle contraction. RESULTS: The area, as a single
      parameter, produced the most significant result in discriminant analysis, about
      80% MUPs from neurogenic muscles being judged to be abnormal. Compared with the
      area, the amplitude and duration were less sensitive, being able to assign about
      77% and 70% of MUPs in the neurogenic group as abnormal. A combination of the
      area/amplitude ratio (thickness) and the amplitude, and a combination of the
      duration (width) and the amplitude could further improve the discriminating
      ability, around 80% and 81% MUPs in the neurogenic muscles being classified as
      abnormal by the combinations. The simplified discriminant functions, 2 x Log10
      (amplitude) +Log10 (area/amplitude) -4 for size index, and 5 x Log10 (duration) +
      3 x Log10 (amplitude) -10 for width-height index had same discriminating ability
      as the real discriminant function. CONCLUSIONS: The new parameters, SI, WHI and
      area in spike-triggered EMG seemed to be promising, since they produced a better
      yield in the diagnosis of neurogenic lesions than amplitude or duration alone in
      the discriminant analysis.

PMID- 9772479
TI  - [Effects of captopril on the tissue nitric oxide synthase in off spring from
      treated pregnant SHRs].
AB  - OBJECTIVES: To further clarify the anti-hypertensive mechanism of captopril and
      explore a new method for earlier prevention and treatment of hypertension, we
      studied the effects on tissue nitric oxide/nitric oxide synthase (NO/NOS) of the
      descendants of spontaneously hypertensive rats (SHRs) by earlier captopril
      treatment. METHODS: After the pregnant SHR was treated by captopril (100 mg.kg
      1.d-1), the systolic blood pressure (SBP), NOS activity and expression of
      inducible and constitutive NOS (iNOS and cNOS) in brain cortex, renal cortex,
      heart ventricle of their descendant were detected by tail-cuff sphyg-momanometer,
      liquid scintillation and reverse transcription-polymerase chain reaction method
      respectively. RESULTS: Compared with that of non-treated SHR, SBP of treated SHR
      was decreased (P < 0.01) and NOS activity of renal cortex, heart ventricle, iNOS
      expression of brain cortex, cNOS expression of renal cortex, heart ventricle
      significantly increased (P < 0.05). CONCLUSION: The results suggested that
      earlier captopril treatment could increase NOS activity and expression in
      different tissues of SHR, which might be a new anti hypertensiven mechanism.

PMID- 9772481
TI  - [Relation between accumulation of multiple gene variation and cancer onset and
      development].

PMID- 9772480
TI  - [Effect of donor antigen-TCS on survival time of mouse to rat cardiac
      xenografts].
AB  - OBJECTIVE: To induce specific mouse to rat xenograft tolerance. METHODS: The
      antibodies affinity chromatography was used to purify mouse major
      histocompatibility complex antigens (H-2 Ag). H-2 Ag was conjugated with
      trichosanthin (TCS) by heterobifunctional reagents SPDP and 2-IT. The specific
      inhibition function of H-2 Ag-TCS to recipient immune cell was Measured. H-2Ag
      TCS was used in mouse to rat cardiac xenotransplantation (cuff technique).
      RESULTS: The proliferation of recipient immune cell pretreated with conjugate H
      2Ag-TCS was inhibited. H-2 Ag-TCS significanlly prolonged the cardiac survival
      time (6.88 +/- 1.36) compared with CgA group (2.83 +/- 0.75) (P < 0.01).
      CONCLUSION: H-2 Ag-TCS can induce specific tolerance to xenograft.

PMID- 9772482
TI  - [Clinical uses of antibiotics: problems and tactics].

PMID- 9772483
TI  - [Carrying out energetically. Good Clinical Practice (GCP)].

PMID- 9772484
TI  - [Trends and changes in antimicrobial resistance of clinical isolates from 11
      hospitals in Beijing area].
AB  - OBJECTIVE: To study the antimicrobial resistance and its changes of clinical
      isolates in Beijing area. METHODS: The diameters of the inhibition zones of
      clinical isolates around antibiotic susceptibility test discs at 12 hospitals in
      Beijing area were computerfiled and analysed by the software of 'WHONET'
      according to NCCLS published in 1994. RESULTS: A total of 10,305 isolates were
      collected in 1995. The percentages of resistance were as follows: (1) in E. coli:
      amikacin, 8%, ceftazidime, 15%, the other third generation cephalosporins, about
      30%, (2) in Klebsiella spp: ofloxacin, 0%, ceftazidime, 15%, ciprofloxacin, 17%,
      norfloxacin, 15%, ofloxacin, 5%, (4) in Staph. aureus: norvancomycin, 0%, (5) in
      Strep. pneumoniae: penicillin G, 9%, (6) in Enterococcus spp: norvancomycin, 7%.
      The antimicrobial resistant changes over a six year period from 1990 to 1995 were
      surveyed and it was found that resistant percentage of the most isolates to
      quinolones, for example norfloxacin, increased significantly year by year and no
      remarkable differences of resistance to antimicrobial agents but quinolones were
      observed in Ps. aeruginosa. CONCLUSION: Antimicrobial resistance should be
      emphasised during clinical therapy with antimicrobial agents, and trends in
      antimicrobial resistance of isolates should be followed.

PMID- 9772485
TI  - [Changes in patterns and resistances of bacteria from 731 patients with
      bacteremia in 11 years].
AB  - OBJECTIVE: To study the changes in patterns and resistances of bacteria from
      patients with bacteremia in 11 years. METHODS: Diffusion tests were used to
      measure the antibiotic sensitivity of bacteria isolated from the patients with
      bacteremia. RESULTS: The proportion of staphylococcus epidermidis in bacteremia
      increased significantly. The proportion of methicillin-resistant Staphylococcus
      aureus (MRSA) in bacteremia caused by staphyiococcus increased markedly.
      Resistance of MRSA and methlcillin-sensitive staphylococcus aureus (MSSA) to
      penicillin, and gentamycin increased significantly. Compared 1986-1990, with 1991
      1996, the resistance of S. epidermidis to penicillin, erythromycin and
      methicillin increased markedly, so did resistance of pseudomonas aeruginosa to
      carbenicillin, and piperacillin, resistance of E. coli to gentamycin and
      cefoperazone, resistance of klebsiella to ampicillin and carbenicillin. The
      resistance of enterobacteriaceae which induced beta-lactamase to the first to the
      third generation of cephalosporins was relatively high. CONCLUSION: The
      resistance of bacteria to the commonly used antibiotics was produced in various
      degrees.

PMID- 9772487
TI  - [A recombinant autoantigen U 1 RNP 70,000: expression in E. coli. and its
      serodiagnostic application].
AB  - OBJECTIVE: To express the recombinant autoantigen U 1 RNP 70,000 and to evaluate
      its serodiagnostic value. METHOD: We used molecular cloning techniques and
      immunoblotting technique. RESULTS: The recombinant proteins had authentic U 1 RNP
      70,000 antigenicity, with the molecular weight corresponding to their theoretical
      value. 112 of 115(97.4%) anti-70,000 positive sera(IBT) could be detected by r
      70,000. CONCLUSIONS: r 70,000 has good specificity and can be used in further
      detailed epitopes mapping. r 70,000 can be put into use for serodiagnostic
      detection.

PMID- 9772486
TI  - [Observation of 212 cases of typhoid fever treated with FQNS].
AB  - OBJECTIVES: To treat 212 cases of typhoid fever with Seven kinds of
      fluoroquinolones (FQNS) and to evaluate their clinical efficacy, bacterial
      susceptibility and adverse drug reaction (ADR). METHODS: All the cases were
      hospitalized and uniantibiotic treated in which NFX group (n = 43) was compared
      with CP group (n = 28). RESULTS: 204/212 (96.23%) cases were positively cultured.
      All except 9 (S. paratyphi) were S. typhi. Of the 212 clinically isolated
      strains, 194(91.51%) were susceptible to FQNS with K-B assay. The MIC except 1
      (6.25 mg/L) were all < or = 4 mg/L. The results of MIC detection with 20 strains
      of clinically isolated bacteria in 1994 and 1995 showed that FQNS were apparently
      superior to other antityphoid fever antibiotics as chloramphenicol and
      cefoperazone. When FQNS were used the overall clinical cure rate was 98.11%, the
      bacterial clear rate was 99.51%, and the rate of ADR was 11.3%. No difference was
      found between the NFX group and CP group in defervescent days and the cure rates
      and bacterial carrier state in recovery. The rate of recurrence and ADR in the
      NFX group was lower than that in the CP group. With the improvement of
      pharmacokinetics, new FQNS can be administered once or twice a day, and the
      therapy course shortened from 14 to 7 days. It is considered that FQNS are
      currently the first choice of antibacterials in treating typhoid fever.

PMID- 9772488
TI  - [Identification of a novel missense mutation in Wilson disease gene].
AB  - OBJECTIVE: To investigate the allelic heterogeneity of ATP 7 B gene in Chinese
      patients. METHODS: Exons of ATP7B gene from patient's DNA were amplified with PCR
      technique. Mutations were screened by single strand conformation polymorphism
      (SSCP) analysis and further confirmed by sequencing. RESULTS: The molecular
      structure of exon 7 of the ATP7B gene from 141 WD patients was preliminarily
      analyzed. A similar band shift of 4 encephalopathy type patients was identified
      with SSCP and sequencing. There was a missense mutation, Ser 662 Cys, which was
      caused by a C to G transversion at the second base of the codon. CONCLUSIONS: The
      mutations of Chinese ATP7B gene were investigated for the first time in China and
      a novel missense mutation was identified.

PMID- 9772489
TI  - [Suppression of transforming growth factor beta 1 on malignant phenotype in HL-60
      cells].
AB  - OBJECTIVE: To study the effect of transforming growth factor beta 1 on tumor
      cells. METHOD: HL-60 cells were transfected with transforming growth factor beta
      1 expression vector by electroporation. Stable cell clones resistant to G 418
      were obtained after 2-3 week growth with the drug-containing medium. A series of
      malignant phenotype were compared between transfected and untransfected HL 60
      cells. RESULTS: The growth speed of HL-60 cells which overexpressed transforming
      growth factor beta 1 mRNA decreased significantly. Clonigenecity in soft agarase
      and tumor formation in athymic mice were lower than those untransfected HL-60
      cells. CONCLUSION: Suppression effect of transforming growth factor beta 1 on
      malignant phenotype in HL-60 cells were demonstrated.

PMID- 9772490
TI  - [Exogeneous adenosine triphosphate promotes proliferation of renal tubular
      epithelial cells].
AB  - OBJECTIVE: To investigate the effect of exogeneous ATP on proliferation of renal
      tubular epithelial cells (LLC-PK1) and its intracellular mechanisms. METHODS: DNA
      synthesis was measured by 3H-thymindine incorporation, and proliferation was
      assessed by cell counting. MAP kinase activity was detected by phosphorylate
      specific substrate MBP. RESULTS: Exogeneous ATP (1-1000 mumol/L) significantly
      increased 3H-TdR uptake in a concentration dependent manner. It also increased
      cells proliferation. 100 mumol/L ATP rapidly activated MAP kinase. The potency of
      LLC-PK1 proliferation stimulated by ATP was similar to the effect of polypeptide
      growth factor EGF. Adenosine was less stimulatory effective than ATP. NBTI (50
      mumol/L), an inhibitor of memberous nucleotide transportor, did not reduce the
      effects of ATP or Ado on proliferation of these cells. CONCLUSIONS: Extracellular
      ATP is a potent mitogen of LLC-PK1 cells, and may promote stimulatory effect of
      EGF in these cells. This mitogenic effect is unlikely induced by ATP entering
      cells, but may be mediated by purinergic receptors which activate signaling
      pathway through MAP kinase cascade.

PMID- 9772492
TI  - [The effects of removing circulated TNF by immunoadsorption on renal changes in
      rabbits with endotoxin shock].
AB  - OBJECTIVES: To remove circulating tumor necrosis factor (TNF) by specific
      immunoadsorption column containing anti-TNF monoclonal antibody (McAb) and
      observe the effects of the therapy on renal changes in experimental endotoxin
      shock. METHODS: New Zealand white rabbits were injected with lethal dose of E.
      coli endotoxin (LPS, 8 x 10(9) cfu/kg) to produce endotoxin shock, then were
      divided into two groups: control (n = 7) and perfusion group (n = 10). Perfusion
      was started at 1 hour after administration of endotoxin. Mean arterial pressure
      (MAP) was monitored continuously. Blood samples were collected for assay of TNF,
      urea nitrogen (BUN) and creation (Cr). Six hours after infusion of LPS, rabbits
      were sacrificed, then the kidney was taken for pathologic observation. RESULTS:
      MAP was increased 30 minutes after perfusion in perfusion group, then kept at a
      level higher than that in the control group in the monitoring period (P < 0.01).
      The plasma TNF activation was reduced significantly in the perfusion group (44 +/
      10) compared with the control group (1448 +/- 226, P < 0.05) one hour after
      perfusion. The levels of BUN and Cr were decreased in the perfusion group
      compared with the control group. The degree of glomerular congestion and
      infiltration of leukocytes in glomeruli was significantly lower in the perfusion
      group than in the control group. The degree of tubular necrosis was decreased
      significantly in the perfusion group compared to that in the control group (P <
      0.05). The mitochondrial ultrastructural changes were more severe in the control
      group than in the perfusion group. CONCLUSIONS: Specific immunoadsorptive column
      containing anti-TNFMcAb could remove effectively circulating TNF in experimental
      endotoxin shock. Reducing levels of TNF in the early phase of endotoxin shock may
      ameliorate the state of hypotension.

PMID- 9772491
TI  - [Changes of inflammatory mediator in aucte necrotizing pancreatitis and effect of
      somatostatin analogne stilamin in rats].
AB  - OBJECTIVES: To investigate the changes of inflammatory mediator in ANP and to
      explore the effectiveness of stilamin treatment on ANP. METHODS: SD rats were
      divided into experimental groups (ANP = 12, ANP + NS = 10, ANP + Stilamin = 12)
      and control group (NC = 10). Rat ANP models were made by retrograde injection of
      3.5% sodium taurocholate 2.5 ml/kg into the pancreatic duct, and treated by
      intravenous injection of stilamin 84 micrograms.kg-1.d-1 or same amount of normal
      saline respectively. Serum IL-1 beta, IL-6, IL-12, TNF-alpha, PLA2, amylase and
      endotoxin were examined. Finally, the morphology and pathology of the pancreas,
      liver, lung, heart and kidney, as well as the electronmicroscopical investigation
      of liver and lung cells were observed. RESULTS: The mean IL-1 beta, IL-6, IL-12,
      TNF-alpha, in the ANP and ANP + NS group were higher than those in the ANP +
      stilamin group and Control group (P < 0.01). The endotoxin, amlyase, PLA2 level
      in the ANP + stilamin group was lower than those in the ANP and ANP + NS groups
      (P < 0.001). ANP significantly increased white blood cell chemotax and
      infiltration, as well as hemorrhagic focus in liver, kidney and lung, but the
      pathological examinations of the liver, pancreas, lung and kidney demonstrated
      much less destruction in the stilamin group. CONCLUSIONS: Inflammatory cytokins
      play an essential role to induce pathophysiological process of ANP, and its
      related MODS may be effectively prevented and treated by stilamin.

PMID- 9772493
TI  - [Elimination of nitrogen dioxide and nitric oxide by soda lime and its
      components].
AB  - OBJECTIVES: To investigated the efficacy of soda lime and its components in
      absorbing NO2 and NO. METHODS: VIP BIRD ventilator was connected with Siemens
      test lung. While the concentration of inhaled NO was 80 mg/L, the inspired gas
      passed through soda lime or its component. NO and NO2 were measured before and
      after testing materials in the circuit. Test 1, the soda lime canister
      sequentially was filled with smaller particle soda lime 500, 250, 125, 62.5, 39,
      20, 10 and 0 g, to determine weight-efficacy relationship of the soda lime. Test
      2, the canister sequentially was filled with bigger particle soda lime 500, 62.5,
      30, 20 and 10 g, for comparing effective absorption of NO and NO2 between the two
      types of soda lime Test 3, 1.0 g methyl orange was added to smaller particle soda
      lime 10 g and 20 g respectively to observe its effect on eliminating NO and NO2.
      Test 4, silica gel tube was filled with smaller particle soda lime 10 g, KOH 10
      g, NaOH 10 g, Ca(OH)2 2.5 g, and methly orange 0.5 g respectively for observing
      their ability of eliminating NO and NO2. RESULTS: The two types soda lime had the
      ability to eliminating NO and NO2 from inspired gas with a positive relationship
      with its weight. Both KOH and NaOH did not eliminate NO and NO2 Ca(OH)2 and
      methyl orange had a week ability. Methyl orange did not affect the ability of
      soda lime to eliminate NO2, but decreased its ability to eliminate NO. During 240
      min, the eliminating NO2 ability of soda lime did not change, but the eliminating
      NO ability was reduced from 30% to 19% after 60 min. CONCLUSIONS: The effective
      components to eliminate NO and NO2 in soda lime are Ca(OH)2 and NaOH. Their
      ability to eliminate NO and NO2 increases with increase in their weight. The
      ability to eliminate NO decreases with increase in the contacting time with NO.

PMID- 9772495
TI  - [The relationship between in vitro chemosensitivity of human breast cancer to MDR
      related drugs and expression of mdr-1 gene].
AB  - OBJECTIVE: To study the relationship between in vitro chemosensitivity of human
      breast cancer to MDR related drugs and expression of mdr-1 gene. METHODS: We
      measured the chemosensitivity of 56 human breast cancers to MDR related drugs by
      MTT assay in vitro and level of mdr-1 mRNA in these samples by RT-PCR technique.
      RESULTS: The expression of mdr-1 gene in the breast cancer resistant to drugs in
      vitro was increased significantly. The level of mdr-1 mRNA was not correlated
      with Imax%, but correlated with IC50 statistically. CONCLUSION: These results
      support that the increased expression of mdr-1 gene is a major cause of
      resistance to MDR related drugs.

PMID- 9772494
TI  - [The effect of endothelin and protein kinase C on the vasoactive mechanisms of
      beta A(4)25-35 at skin microvasculature].
AB  - OBJECTIVE: The aim of the present study is to investigate the mechanisms of beta
      A(4)25-35 at the level of skin microvascula ture. METHODS: Using a blister model
      in rat skin, we examined the possibilities that beta A(4)25-35 induces VC effect
      via the release of endothelin and the involvement of protein kinase C (PKC).
      Changes in microvascular blood flow were monitored using laser Doppler flowmetry
      and the area within the response curve measured. RESULTS: The results showed that
      either the endothelin receptor antagonist (BQ--123 at 10 mumol) or PKC inhibitor
      (bisindolylmaleimide at 1 mu mol) was perfused before beta A(4)25-35. It
      prevented beta A(4)25-35 from inducing a VC effect and allowed a subsequent SP to
      induce a normal response. CONCLUSION: Both endothelin and PKC play a role in the
      mechanism be which beta A(4)25-35 induces VC effect and modulates subsequent SP
      response at the level of skin microvasculature. We suggest the possibility that
      the vascular activity of beta A(4)25-35 could be mediated via endothelin with
      subsequent activation of PKC.

PMID- 9772496
TI  - [Abrogated or decreased tumorigenicity and metastasis induced by retroviral
      mediated B7.1 gene transfer on murine tumors with different immunogenicity].
AB  - OBJECTIVE: To investigate the differences of tumorigenicity and metastasis of
      marine tumors with different immunogenicity by B7.1 gene transfer. METHOD: Using
      retroviral-mediated gene transfer, we transduced B7.1 cDNA into a panel of murine
      tumor lines with different immunogenicity to study the effect of B7.1
      costimulation on antitumor immunity. RESULTS: After transduced with B7.1 cDNA,
      the immunogenic T lymphoma EL4 regressed completely, and tumorgenicity of three
      nonimmunogenic tumors melanoma B16, mastocytoma P815 and mammary adenocarcinoma
      MA891 were significantly reduced in syngeneic mice. The experimental metastasis
      of B16 and spontaneous pulmonary metastasis of MA891 were profoundly suppressed.
      Moreover, immunization with B7.1 cDNA transduced B16 induced systemic immunity
      against subsequently inoculated parental B16 tumor, while this immunization
      method did not provide protective immunity against established parental B16
      tumor. CONCLUSION: Our results show that varied extent of antitumor immunity can
      be induced to abrogate or decrease tumorigenecity and metastasis through B7.1
      gene transduction, depending on the immunogenic potential of tumors.

PMID- 9772497
TI  - [The relationship between autoimmune thyroiditis and TNF alpha: a preliminary
      study].
AB  - OBJECTIVE: To observe the action of tumor necrosis factor-alpha (TNF alpha) in
      the pathogenesis of autoimmune thyroiditis. METHODS: The activity of TNF alpha of
      peripheral blood mononuclear cells was detected in 25 cases of autoimmune
      thyroiditis, 9 cases of Grave's disease, and 18 normal controls by ELISA and
      bioassay. RESULTS: The activity of TNF alpha in patients with autoimmune
      thyrioditis was significantly higher than that in normal controls (P < 0.001),
      and in patients with Grave's diseases significantly lower than that in normal
      controls (P < 0.01). TNF alpha activity detected by two methods showed a good
      correlation (r = 0.972 P < 0.001). There were a negative correlation between TNF
      alpha and TT3 or FT3 (r = -0.437, -0.432 respectively, both P < 0.05) and a
      positive correlation between TNF alpha and TPO-Ab or TGA (r = 0.53, 0.51
      respectively, both P < 0.01). TNF alpha activity was not associated with the
      period of disease and the size of thyriod. CONCLUSION: TNF alpha exerts an
      important role in the pathogenesis of autoimmune thyroiditis.

PMID- 9772498
TI  - [Expression of the integrin alpha 5 subunit in hepatocellular carcinoma].
AB  - OBJECTIVE: To elucidate the roles of integrins in tumorigenesis, progression,
      differentiation, invasiveness and metastasis, and the role of the integrin alpha
      5 subunit in hepatocellular carcinoma (HCC). METHODS: 79 formalin-fixed sections
      of hepatocellular carcinoma (HCC) were obtained. The integrin alpha 5 subunit was
      measured by immunohistochemistry assay (ABC method). RESULTS: In 79 cases of HCC,
      cancerous tissues had lower expression than their adjacent non-tumor tissues
      (32.9% vs 81.0%, P < 0.01). The alpha 5 positive rate in small HCC (= < 5 cm in
      diameter) was higher than large HCC > 10 cm in diameter), being 55.6% and 10.0%
      respectively. Well-differentiated HCC expressed higher alpha 5 than poorly
      differentiated ones. The alpha 5 positive rates were lower in highly invasive HCC
      than those to low invasive ones. CONCLUSION: Our study indicated that expression
      of the integrin alpha 5 subunit is correlated with growth, differentiation,
      invasiveness and metastasis of HCC. It is possible that alpha 5 subunit is a
      negative regulator to these biological parameters of HCC.

PMID- 9772500
TI  - [Enhance the diagnostic level of primary hyperparathyroidism in China].

PMID- 9772499
TI  - [Diagnosis and treatment of ectopic pregnancy should be strengthened].

PMID- 9772501
TI  - [Intervention approach and its effect on lowering mortality of ectopic pregnancy
      in Shanghai].
AB  - OBJECTIVE: To explore an effective intervention approach to lower the mortality
      of ectopic pregnancy. METHODS: We monitored the mortality of ectopic pregnancy
      during 1987-1995 in Shanghai and experts' audit, focusing on the causes of death
      from ectopic pregnancy and combining official administration with intervention
      approach in medical institutions. RESULTS: Misdiagnosis and patient's delay to
      hospital were the causes of death from ectopic pregnancy. There were 523,299 live
      births in Shanghai from 1987 to 1989, in which 23 cases died from ectopic
      pregnancy, with a mortality of 4.40/100,000. After implementing the intervention
      approach, during 1990-1995, 14 cases of the total 625,206 nancies live birth died
      from ectopic pregnancy, with a mortality of 2.24/100,000, as compared the two, P
      < 0.05. Accordingly, ectopic pregnancy as the cause of maternal death dropped
      from the first leading cause to the fourth. CONCLUSION: Intensive health care
      education in masses, medical staffs' awareness to ectopic pregnancy, and
      intervention, early hospitalization, early diagnosis and early therapy can lower
      the mortality of ectopic pregnancy.

PMID- 9772502
TI  - [Relationship between microsurgical tubal reversal and ectopic pregnancy].
AB  - OBJECTIVE: To study the correlation between microsurgical tubal reversal after
      tubal sterilization and ectopic pregnancy. METHODS: 1029 women who underwent
      microsurgical tubal reversal were followed up. The causes of ectopic pregnancy
      were analysed and discussed. RESULTS: 960 intrauterine pregnanciess and 12
      ectopic pregnancies occurred. The 12 ectopic pregnancies were all tubal ones,
      among which 2 had intrauterine pregnancies. The rate of ectopic pregnancy in the
      1029 women was 1.17%, and in the pregnant cases was 1.23%. The ratio of
      intrauterine pregnancy to ectopic pregnancy was 1:80. The rates of ectopic
      pregnancy in the 1st, 2nd year and 2 years later after tubal reversal were not
      significantly different respectively among the tubal reversal and among the
      pregnant cases. The rates of ectopic pregnancy in the 1st and 2nd 6 months after
      tubal reversal were not statistically different. The early tubal hydrapertubation
      could only increase the chance of ectopic pregnancy. The sterilization method,
      reversal mode, and interval between sterilization and reversal were not related
      to the ectopic pegnancy. CONCLUSION: When the lesion in the sterilized position
      is completely removed, the sutures being through the tubal mucosa and the early
      tubal hydrapertubation not carried out, the chance of ectopic pregnancy can not
      be increased after tubal reversal. The contraception 6 months after tubal
      reversal is not related to ectopic pregnancy.

PMID- 9772503
TI  - [Early diagnosis of ectopic pregnancy by uterine curettage with serum hCG assay].
AB  - OBJECTIVE: To explore the value of uterine curettage combined with serum hCG
      assay in the diagnosis of early ectopic pregnancy (EP). METHODS: Judgement was
      done by uterine curettage pathologic examination of uterine content and
      determination of serum hCG in 61 patients with suspected EP with clinical
      symptoms, signs and auxillary examinations. RESULTS: Intrauterine pregnancy was
      confirmed in 17 patients by the presence of chorionic villi in the uterine
      contents. 26 patients were diagnosed as having EP by the absence of chorionic
      villi and elevated levels of hCG 24 hours after curettage. 18 patients who had no
      chorionic villi and the level of hCG fall down spontaneously after curettage were
      diagnosed having either intrauterine pregnancy or EP, mostly no further
      intervention. CONCLUSION: Diagnostic curettage with serum hCG determination can
      be used for differentiating intrauterine pregnancy from EP and it can also
      provide a reference for further arrangement.

PMID- 9772504
TI  - [Clinical characterizations of familial diabetes mellitus associated with
      mitochondrial gene mutation].
AB  - OBJECTIVE: To discuss clinical features at diabetic subtype which is apparently
      caused by a single mutation in the mitochondrial tRNA(Leu(UUR)) gene. METHODS:
      According to WHO criteria of diabetes mellitus (DM), 130 patients with DM and the
      family history of DM (either NIDDM or IDDM) were screened by using genetic
      diagnosis. Clinical and laboratory analyses were made in three unrelated patients
      with the mutation in mtDNA and their relatives. RESULTS: Four unrelated subjects
      (3.1%) were detected with mutation at position 3243 of mitochondrial DNA. The
      nine diabetes patients from first degree relatives of three probands were also
      identified with the mutation, in which eight patients were associated with
      sensory hearing loss and required insulin therapy due to secondary failure to
      oral hypoglycemic agents. All these nine patients had a lower frequency of
      obesity in the past, and most of them had a mother with diabetes, were younger at
      diagnosis, and were generally accompanied by in paired insulin secretion.
      CONCLUSION: Since the patients have the clinical characteristics of maternal
      transmission, hearing loss and impaired insulin secretion, we conclude that
      maternally inherited diabetes and deafness (MIDD) is a new diabetes subtype
      associated with a single mitochondrial mutation.

PMID- 9772505
TI  - [In vitro expansion of human umbilical cord blood hematopiotic cells and its
      subpopulation].
AB  - OBJECTIVE: To study the effect of expansion of cord blood stem cells in vitro.
      METHODS: The mononuclear cells of human umbilical cord blood was cultured in
      vitro and the cell cycle and CD34+ subset analysis was performed on these cell
      preparations using flow cytometry. RESULTS: After 35 days, the number of
      nucleated cells showed over a comulative 252 fold expansion. CD34+ cells
      increased 50-fold in 7-21 days. CD33+ cells increased 280-fold during 7-28 days.
      CD19+ and CD34+ cells disappared after 14 days. The cells remained in G0/G1 phase
      and increased in the S phase. CONCLUSION: Single umbilical cord blood would be
      enough to transplant to adults if suitable time and a novel expansion strategies
      are set.

PMID- 9772506
TI  - [Transfer and expression of antisense genes of hepatitis B virus (HBV) and their
      anti-HBV effects].
AB  - OBJECTIVE: To observe the transfer and expression of HBV antisense genes and
      their anti-HBV effects in 2.2.15 cells mediated by retroviral vector-packaging
      cell line system. METHODS: The recombinant retroviral vectors mediating
      expression of HBV antisense RNA complementary to 1402-2906 fragment (preC/C) or
      2839-1986 fragment (preS/S) of HBV DNA were used to transduce into NIH 3T3 cells
      and 2.2.15, respectively. Then, the total RNAs of tranduced NIH 3T3 cells were
      extracted and hybridized with HBV DNA probe. The HBsAg and HBeAg in the
      supernatants of cultured 2.2.15 cells were assayed with RIA method and the DNAs
      were hybridized with HBV DNA probe by dot blot. RESULTS: The results showed that
      the HBV antisense genes could be transfered into and expressed in the NIH 3T3
      cells mediated by recombinant retroviral vector packaging cell line (PA317 cell).
      The inhibitory effects on the expression of HBV antigens by antisense RNAs
      appeared as early as on the day 3 after transduced, reached peak level on the day
      5, and persisted at least for eleven days. The inhibitory rates of HBsAg and
      HBeAg were 71% and 23% by antisense preS/S, and 23% and 59% by antisense preC/C
      on the day 5 after transduction. In comparison to blank control or sense--gene
      expressing vectors, the inhibitory effects of HBV antisense vectors were highly
      significant (P < 0.01). HBV DNA level in the supernatant of the 2.2.15 cells
      transduced with either antisense preS/S or preC/C in comparison to the blank
      control vectors was also reduced on the day 5 after transduction as detected by
      DNA dot blot assays, but the viability of transduced 2.2.15 cells was not
      affected as detected by MTT assays. CONCLUSIONS: HBV antisense genes can be
      transfered and expressed in the eukaryotic cells and the expression of HBV
      antisense RNAs in 2.2.15 cells can inhibit the replication and expression of HBV.

PMID- 9772507
TI  - [Clinical significance of detection of PML-RAR alpha fusion gene of APL during
      differentiation therapy with ATRA].
AB  - OBJECTIVE: To characterize of the expression patterns of PML-RAR alpha fusion
      gene during differentiation therapy with ATRA. METHODS: A "neated" RT/PCR was
      established and subsequently used to study on 74 Acute Promyelocytic Leukemia
      (APL). RESULTS: Two major isoforms (type S and L) were detected in leukemia cells
      from 44 novel patients with APL. 19 of 44 (43.2%) patients with type S isoforms
      were accompanied with poor prognosis. 15 cases were detected sequentially by the
      RT/PCR method for dynamic observation of MSD during postremission therapy with
      ATRA and chemotherapy alternatly. The positive rate was 46.7% in 6 months after
      CR, then the positive rate curve tended to down wards gradually from 33.5% (12
      months after CR) to 26.7% (24 months after CR), 11.1% (36 months after CR), 8.3%
      on 48 months after CR. Other 30 cases of APL which are long-term survivals and
      received the same postremission program were detected by the RT/PCR method. The
      expression of the fusion gene reversed positivty in two cases on 56 and 60 months
      respectively, then both relapsed. One case was detected regularly once a year for
      3 times. In another case, the fusion gene was detectable whoever was no any
      abnormal evidence in peripheral blood and bone marrow 26 cases were negative and
      had a long-term survival CCR of 47-114 months (medium 66). CONCLUSION: The
      detection of RT/PCR PML-RAR alpha fusion gene plays an important role in clinical
      diagnosis, evaluation of prognosis and prediction of relapse in APL.

PMID- 9772508
TI  - [Construction, expression and activity of a single chain antibody to gastric
      cancer cells].
AB  - OBJECTIVE: To construct single chain antibody from McAb 3H11, which has been
      successfully used in clinical radioimmunoimage, for its widel application in
      biological treatment of human cancer. METHOD: Reversetranscription and polymerize
      chain reaction (RT-PCR) were used to clone the V region genes of McAb 3H11 (VH,
      VL). The cloned VH and VL were sequenced and recombined through a (Gly4Ser) 3
      linker. The constructed single chain antibody gene was joined with glutathione-S
      transferase gene (gst) and its fusion proteins (GS3H11) were expressed in E.
      coli. The activity of GS3H11 was characterized with competition experiments after
      its denature and renature treatment. RESULTS: The recombinant GS3H11 was highly
      produced in inclusion bodies and the activity was recovered after being
      renatured. The competition experiments showed that GS3H11 could competitively
      inhibit the McAb 3H11 binding to gastric tumor cells MGC803. The inhibition was
      complete when the molecular ratio of GS3H11 to McAb 3H11 reached to 30:1.
      However, the GS3H11 did not interfere in binding of McAb PD4 and 3G9 to MGC803.
      CONCLUSION: The specific binding activity of McAb 3H11 is retained in single
      chain antibody which is potentially useful for therapeutic application.

PMID- 9772509
TI  - [Changes in gamma-amino-butyric acid and N-methyl-D-aspartic acid receptor-gated
      currents from freshly isolated hippocampal CA1 pyramidal neurons of hepatic
      encephalopathy rats].
AB  - OBJECTIVE: To explore the effects of the changes of the amino acid receptor-gated
      ion-channel currents on the pathogenesis of hepatic encephalopathy (HE). METHODS:
      Using rapid drug applicating device, we added 50 mumol/L gamma-amino-butyric acid
      (GABA) or 1 mmol/L N-methyl-D-aspartic acid (NM-DA) + 10 mumol/L Glycine (Gly) to
      the surrounding of freshly isolated rat hippocampal CA1 pyramidal neurons to
      induce receptor-gated ion-channel currents, which was recorded by whole-cell
      voltage-clamp technique. RESULTS: The intensity of the GABAA-receptor mediated
      inward Cl- current of hippocampal CA1 pyramidal neurons of HE rats (413.3 +/-
      436.8 pA, n = 31) was stronger than that of the controls (233.4 +/- 179.7 pA, n =
      28, t = 2.1049, P < 0.05), and the appearance of the Cl- current in HE rats was
      more frequent than that in the controls. The intensity of the NMDA-receptor gated
      inward current in HE rats (408.5 +/- 317.2 pA, n = 37) was weeker than that in
      the controls (882.6 +/- 896.5 pA, n = 26, t = 2.5851, P < 0.05), but the
      difference of their channel opening frequency was not significant. CONCLUSIONS:
      The changes of the amino acid receptor-gated ion-channel currents play an
      important role in the pathogenesis of hepatic encephalopathy.

PMID- 9772510
TI  - [The relationship between insulin resistance and abnormalities of cellular
      calcium metabolism and cell membrane abnormalities in patients with essential
      hypertension].
AB  - OBJECTIVE: To investigate the relationship between the insulin resistance (IR)
      and the abnormalities of cellular calcium metabolism and cell membrane in
      patients with essential hypertension. METHODS: Plasma insulin and glucose before
      and during OGTT, membrane ATPase activity, cholesterol (C) and phospholipid (P),
      lipid peroxides (MDA), intracellular total calcium concentration [(Ca2+)i] and
      calcium binding capacity of inner surface of membranes were determined in 26
      normotensive (NT) subjects, 17 hypertensives (HT), and 16 hypertensives
      associated with IR (HT + IR). RESULTS: The HT + IR group had higher levels of
      plasma glucose and insulin than that in the NT group and HT group with
      significant differences. The HT + IR group consistently demonstrated depressed
      activity of each Na(+)-K(+)-ATPase and Ca(2+)-ATPase studied with significant
      differences when compared with the NT group, but no difference was found if
      compared with the HT group. There was a higher [(Ca2+)i] in the HT + IR group
      than those in the NT group and even in the HT group with significant differences,
      respectively. Insulin sensitivity in the HT + IR group was significantly lower
      than that in both groups of HT and NT, respectively. The membrane C/P molar ratio
      and MDA content in the HT + IR group and HT group were significantly higher than
      those in the NT group, respectively. CONCLUSIONS: It is likely that there is a
      causal relation between IR and abnormalities of cellular calcium metabolism and
      membrane lipids in patients with essential hypertension.

PMID- 9772511
TI  - [Partial nucleotide sequencing of 7 hepatitis E virus strains isolated from sera
      of patients with acute sporadic hepatitis E in China].
AB  - OBJECTIVE: To compare partial nucleotide and amino acid sequences between
      epidemic and sporadic hepatitis E viruses (HEV) in China and their relation to
      the frequency of hepatitis E (HE). METHODS: A reverse transcription nested
      polymerase chain reaction (RT-nPCR) was used for the amplication of HEV open
      reading frame 2 (ORF2) cDNA from sera of patients with acute sporadic HE. The RT
      nPCR products of HEV ORF2 cDNA were directly sequenced using a sequenase version
      2.0 kit with the dideoxy sequencing method. RESULTS: 28 of 41 sera of patients
      with acute sporadic HE obtained from Shenzhen, Changchun, Hangzhou, Xian and
      Beijing by RT-nPCR were HEV ORF2 cDNA positive, and 7 of them were sequenced. The
      nucleotide homology of the seven HEV ORF2 cDNA was 78.9%-80.2%, as compared with
      the Mexico strain of HEV (M); 93.1%-95.1% with the Burma epidemic strain of HEV
      (B) (Ep); 92.3%-94.2% with the Burma sporadic strain of HEV (B) (Sp); 96.5%-98.9%
      with the Xinjiang epidemic strain of HEV CH 1.1; and 95.7%-100.0% between them.
      CONCLUSIONS: The seven strains of HEV ORF2 cDNA isolated from sera of acute
      sporadic HE cases have a higher degree of homology with the HEV CH 1.1 and the
      HEV (B), and may belong to HEV (B) subtype, as the HEV CH1.1 does.

PMID- 9772512
TI  - [Etiology of ectopic pregnancy].

PMID- 9772513
TI  - [Current status and countermeasure of gene therapy].

PMID- 9772514
TI  - [Clinical uses of polymerase chain reaction in infectious diseases].

PMID- 9772515
TI  - [The dendritic cell differentiation and antigen-presenting function of the
      erythroleukemia cells induced by GM-CSF].
AB  - OBJECTIVE: To investigate the generation of dendritic cells and the change of
      antigen-presenting function during the differentiation of FBL-3 erythroleukemia
      cells induced by GM-CSF. METHODS: The effects of GM-CSF on the phenotype,
      ultrastructure and antigen-presenting function of FBL-3 erythroleukemia cells
      were observed by FACS, electromicroscopy and 51Cr-release assay. RESULTS: After
      treatment with 100 ng/ml GM-CSF for 3 days, the expressions of 33 D1 and NLDC 145
      which are the specific markers on dendritic cells were increased significantly;
      MHC-II B7-1, B7-2, ICAM-1, VCAM-1 and CD40 were also upregulated. The membrane of
      FBL-3 cells was changed into villous surface with dendritic projections. There
      were plenty of mitochondria in cytoplasm, the nucleus became lobulated. The GM
      CSF-treated FBL-3 cells could apparently stimulate the proliferation of
      allogeneic T lymphocytes, induce the production of IL-2 and improve the specific
      cytotoxic activity of CTL on FBL-3 cells. CONCLUSION: Erythroleukemia cells were
      induced to differentiate into the dendritic cells by GM-CSF and obtained the
      antigen-presenting function.

PMID- 9772516
TI  - [Isolation and identification of DNA fragments frequently deleted from tumor cell
      lines of human esophageal cancer].
AB  - OBJECTIVE: To clone tumor suppressor genes associated with human esophageal
      cancer (EC). METHODS: DNA fragments deleted from cell lines of esophageal cancer
      EC8712 and EC8733 were isolated by using modified genomic substractive
      hybridization. Twenty EC tissues paired with adjacent normal mucosa were analysed
      by Southern blot and PCR with these fragments as probes. RESULTS: Seven DNA
      fragments deleted from EC cell lines obtained were named as 12H1, 12H2, 33H3,
      33H4, 12B1, 33B2 and 33B3. Sequencing revealed their size of 512bp, 428bp, 509bp,
      355bp, 680bp (partially sequencing), 519bp and 425bp, respectively. 12H1 and 33H3
      showed high homology (98%) to a new repeated sequence in human genome. 33H4
      displayed 87% nucleotide identity with human alphoid-like repetitive sequence
      located on chromosome 17. 12B1 was homologous (90%) to LINE 1 transoposon
      containing two open reading frames. 12H2, 33B2 and 33B3 were novel sequences.
      These DNA fragments were deleted in 20%-60% of EC tissues and in 10%-20% of
      adjacent mucosa. CONCLUSIONS: Loss of 33H4 may be accompanied by deletion of an
      adjacent gene. 12B1 as transposon may suppress the tumorigenesis by activating
      suppressor genes or/and by inactivating oncogenes. 12H1/33H3, 12H2, 33B2 and 33B3
      may be candidates of tumor suppressor genes associated with the development and
      the progression of esophageal cancer.

PMID- 9772517
TI  - [Apoptosis in the early stage of compensatory renal growth following
      uninephrectomy in the young and old rats].
AB  - OBJECTIVE: To investigate the role of apoptosis, one of the major factor to
      maintain homeostasis of cell number of organs, in the early process of
      compensatory renal growth, which have been considered to including cellular
      hyperplasia and hypertrophy, following uninephrectomy. METHOD: DNA fragment gel
      electrophoresis, tissue sections photolebeling technique and in situ nick
      translation assay were used to analyze apoptotic cells in the compensatory and
      normal kidney in the young and old Wistar rats. RESULTS: Apoptosis affected
      normal kidney of the old group, but not the young. In the old rat's normal
      kidney, apoptosis index was higher in cortical tubules than that in the medullar
      tubules. In the compensatory remnant kidney, apoptosis was diminished in old
      rats, especially in the cortex, but increased in the young rats, especially in
      the medulla. CONCLUSIONS: Compensatory renal growth includes cellular
      hypertrophy, hyperplasia and apoptosis. In the old, compensatory renal growth is
      mainly cellular hypertrophy, and reduction of cell death. In the young,
      compensatory renal growth is mainly cellular hyperplasia and hypertrophy,
      increased apoptosis may be responsible for the elimination of excess hyperplastic
      renal cell.

PMID- 9772518
TI  - [The relation between expression of PML-RAR alpha gene and effects of ATRA on
      proliferation and differentiation of NB4 cells].
AB  - OBJECTIVE: To study the relation between the PML-RAR alpha gene and the effects
      of ATRA on proliferation and differentiation in acute promyelocytic leukemia cell
      line NB4 cells. METHODS: ASODN-mediated inactivation of the PML-RAR alpha mRNA
      was measured by RT-PCR. The proliferation and differentiation of NB4 cells were
      determined by proliferation curve, morphology, CD antigen of membrane and NBT
      test. NB4 Cell cycle was analyzed by FACS. RESULTS: The inactivation of PML-RAR
      alpha mRNA by ASODN could egnhance the maturation effects and growth suppression
      of ATRA on NB4 cells. The percentage of S phase cell was decreased from 52% to
      29%, and NBT rate increased. All suggest that the sensitivity of NB4 cell to ATRA
      was improved. CONCLUSION: The PML-RAR alpha gene, as a molecular marker of APL,
      is responsible for pathogenesis of APL, and it also decreases the sensitivity of
      ATRA to APL cells.

PMID- 9772519
TI  - [The partial cDNA cloning of a novel gene highly expressed in hepatocellular
      carcinoma].
AB  - OBJECTIVE: To search the novel gene related to human hepatoma. METHODS: Northern
      blot analysis was used to isolate from EST (expressed sequence tags) clones a
      cDNA fragment differentially expressed in hepatocellular carcinoma versus its
      surrounding noncancerous hepatic tissue. Human fetal liver cDNA library was
      screened with EST fragment probe. RESULTS: Northern blot analysis showed that EST
      clone F9391 expressed at high level in all the 6 hepatocellular carcinoma samples
      but low level in the surrounding noncancerous hepatic tissues and 2 normal liver
      tissues. In further screening of human fetal liver cDNA library, we obtained a
      positive clone named FL6. Nucleotide sequencing indicated that FL6 contained 1464
      base pairs and the matched DNA sequence was not found in the gene data bases
      (EMBL 96.6). Northern blot analysis of various fetus tissues with FL6 probe
      showed a high level expression in lung, small intestine, skin and placenta,
      middle level expression in liver, stomach, colon and muscle but low level
      expression in brain, thyroid, thymus, heart, kidney, pancreas and bladder.
      CONCLUSION: The results suggested that FL6 gene related to cell proliferation and
      may play an important role in the process of oncogenesis.

PMID- 9772520
TI  - [Immunophenotypic and clinical features of Philadelphia chromosome positive adult
      lymphocytic leukemia].
AB  - OBJECTIVE: To sutdy the immunophenotypic and clinical features of Philadelphia
      chromosome positive adult acute lymphocytic leukemia (Ph+ ALL). METHODS: Fifty
      one previously untreated Ph+ ALL were included. Morphologic/cytochemistric,
      cytogenetic and immunophenotypic examinations were performed. Patients received
      daunorubicin-vincristine-prednisone (DOP) or DOP-asparaginas (DOLP) induction
      protocols. Two patients received autologous bone marrow transplantation (ABMT) as
      postremission therapy. RESULTS: The 51 patients were among 158 patients with ALL
      (32.3%). Patients with Ph+ ALL were older and had a significantly higher
      incidence of peripheral leukocytosis and blasts, FAB L2 subtype, B lineage
      antigens expression and CD34 positivity. 42.1% of Ph+ ALL achieved complete
      remission (CR). Their remission duration was 4.5 months, the median time to CR
      was 54 days. Two patients receiving ABMT survived in remission 22 and 33 months,
      respectively. CONCLUSION: Patients with Ph+ ALL are usually older, have FAB L2
      morphology, and are B lineage antigens, CD34 positive. These patients had lower
      CR rate, shorter remission duration, and needed longer time to achieve CR.

PMID- 9772522
TI  - [Clinical efficacy of prolonged therapy with NO on patients with pulmonary
      hypertension].
AB  - OBJECTIVE: To determine the safety and clinical efficacy of prolonged NO
      administration in patients with pulmonary hypertension. METHOD: Clinical efficacy
      of prolonged treatment (28 days) with NO (20 ppm) in 17 patients with pulmonary
      hypertension was observed by chest X-ray film, ECG, Doppler echocardiography,
      analysis of arterial blood gases and the other laboratory investigations.
      RESULTS: After prolonged treatment with NO, regurgitation velocity and peak
      pressure gradient across tricuspid valves during systole reduced by 11.8% and
      22.6%, respectively (P < 0.0001). Ejection fraction of right ventricle, stroke
      volume and cardiac output of left ventricle, partial oxygen pressure and oxygen
      saturation of arterial blood increased by 29.9%, 60.3%, 37.8%, 21.7% and 3.8%
      (all statistics; P < 0.0001), respectively. The class of heart function by New
      York Heart Association (NYHA) was improved dramatically (P < 0.01). Heart rate
      also reduced from 96 +/- 12 bpm to 83 +/- 10 bpm (P < 0.0001). But systemic
      artery pressure and the concentration of blood methemoglobin which reflected NO
      toxicity did not change obviously (P > 0.05). CONCLUSION: Clinical efficacy of
      prolonged treatment with NO is satisfied in patients with pulmonary hypertension.
      Significant clinical side effects and toxicities are not seen during prolonged
      treatment with NO.

PMID- 9772521
TI  - [Effect of exercise on glucose transporter gene expression in diabetic rat
      skeletal muscle].
AB  - OBJECTIVE: To investigate the effect of the exercise on glucose transporter 4
      (GLUT4) gene expression in skeletal muscles of rats with streptozotocin-induced
      diabetes. METHODS: Three experiment groups of rats were investigated: diabetic
      non-exercise group; diabetic exercise group; and normal controls. Diabetic
      exercise rats were swim-trained for 6 weeks. The GULT4 mRNA of skeletal muscle
      cells was determined with dot blot. RESULTS: There was weak gene expression of
      GULT4 in diabetic rats, and dot blot revealed that the GLUT4 mRNA decrease 54.9%
      in skeletal muscle cells compared with the normal control. After 6 weeks exercise
      training, the hyperglycemia of diabetic exercise rats decreased significantly
      (from 18.5 +/- 1.9 mmol/L to 14.0 +/- 3.3 mmol/L, t = 4.64 P < 0.01). In muscle
      cells of diabetic exercise rats, the GLUT4 mRNA increased 56% as compared with
      the diabetic rats (t = 15.56, P < 0.01). CONCLUSION: Chronic hyperglycemia may
      inhibit the gene expression of GLUT4 in diabetic rats, which caused the post
      receptor insulin resistance in peripheral tissue. Exercise training can improve
      the impaired GLUT4 expression in diabetic rats, which may contribute to the
      mechanisms of enhanced insulin sensitivity and decreased hyperglycemia in
      diabetics mellitus.

PMID- 9772523
TI  - [The relationship between concentration of growth hormone in serum and
      microangiopathy in patients with diabetes mellitus].
AB  - OBJECTIVE: To study the relationship between growth hormone (GH) and
      microangiopathy in patients with diabetes mellitus in order to elucidate
      pathogenesis on microangiopathy in diabetics. METHODS: GH and insulin (INS) were
      detected by rdioimmunoassay, and blood sugar (BS) was detected by oxydase method.
      RESULTS: 138 NIDDM diabetics were examined. The concentration of serum GH in
      diabetics without microangiopathy (2.3 +/- 1.2 micrograms/L) was higher than in
      normal people (1.0 +/- 1.2 micrograms/L) and GH in diabetics with microangiopathy
      (5.74 +/- 1.94 micrograms/L) was higher than in diabetics without
      microangiopathy. The differences were significant (P < 0.01). As the history of
      diabetes went on, the level of GH in serum increased, and the incidence of
      microangiopathy increased too. The correlation of GH in serum with BS was
      parallel. The correlation of GH in serum with INS was not apparent. 27 ID-DM
      diabetics were examined, their level of GH in serum (6.8 +/- 3.4 micrograms/L)
      was higher than that of NIDDM diabetics (4.6 +/- 1.8 micrograms/L). They were all
      patients with microangiopathy. CONCLUSION: The rise of GH in serum may be an
      important pathogeny that causes microangiopathy in diabetics.

PMID- 9772524
TI  - [Effects of induction of anti-embryonation and anti-fecundity immunity on liver
      granuloma formation in mice infected with Schistosoma japonicum].
AB  - OBJECTIVE: To investigate the effect of anti-fecundity and anti-embryonation
      immunity on liver granuloma formation in mice immunized with soluble immature egg
      antigen (SIEA) of schistosoma japonicum. METHOD: BALB/c mice were immunized with
      the crude SIEA or 26,000-28,000 molecular antigen derived from SIEA and compared
      the size in schistosoma japonicum egg granulomas in the liver after challenge
      infection both the immunized mice and unimmunized controls. RESULTS: The number
      and size of egg granuloma were significantly decreased in mice immunized with
      SIEA and SIEA 26-28,000, by 29.26% and 49.64%, respectively. The inhibitive
      effects on granuloma formation and spleen weights in the group immunized with
      SIEA 26-28,000 were stronger than those in the group immunized with the crude
      SIEA. However, mean granuloma size and spleen weights in the group immunized with
      SEA or SIEA-1 fraction were not different from unimmunized control. CONCLUSION:
      SIEA and SIEA 26-28,000 antigenic molecule play an important role in inhibition
      on liver granuloma formation through their anti-embryonation and anti-fecundity
      immunity effects.

PMID- 9772525
TI  - [The role of urokinase-type plasminogen activator in the pathogenesis of
      pemphigus].
AB  - OBJECTIVE: To investigate the changes of urokinase-type plasmino-gen activator (u
      PA) in the process of acantholysis in pemphigus and observe the influence of
      purified urokinase on the cultured skin explant. METHODS: The expression of
      urokinase antigen on the pemphigus organ model was revealed by
      immunohistochemical method; PA activity was assayed in the acantholysis model;
      the influence of urokinase on the epidermis was observed by adding purified
      urokinase into the cultured skin explant. RESULTS: PA activity was elevated in
      the acantholysis model at 24 hour and was continuing its increase at 48 and 72
      hours. The expression of urokinase was high in the epidermis of pemphigus organ
      model; purified urokinase could induce acantholysis like changes. CONCLUSION:
      Pemphigus antibody induces acantholysis through activating keratinocytes. The
      latter secretes an elevated u-PA, which locates on the membrane of the epidermal
      cells producing a limited pro-teolysis which damages the cohesion of epidermal
      cells.

PMID- 9772526
TI  - [Influence of prenatal exposure to low levels of lead on the neuro-behavioral
      development of neonates].
AB  - OBJECTIVES: To study the effects on the neuro-behavioral development of neonates
      exposed to low levels of lead in utero. METHODS: 131 neonates were selected and
      their umbilical blood lead level was determined by Atomic Absorption
      Spectrometer. The neurobehavioral-cognitive performance of neonates was evaluated
      by Neonatal Behavioral Neurological Assessment (NBNA). RESULTS: NBNA scores in
      neonates with blood lead levels greater than or equal to 0.29 mumol/L were
      markedly lower than those with less than 0.14 mumol/L, and the difference was
      highly significant. CONCLUSION: Blood lead levels of less than 0.48 mumol/L could
      still have harmful effects on the development of children.

PMID- 9772527
TI  - [Gene transfer DNA drugs directed into skeletal muscle and its uses in
      cardiovascular diseases].

PMID- 9772528
TI  - [Study on metastasis of cancer: current status and prospects].

PMID- 9772529
TI  - [Some aspects in the diagnosis and treatment of lymphatic metastasis in stomach
      and colonic cancer].

PMID- 9772530
TI  - [Metastasis of cancer: model establishment and relevant standard].

PMID- 9772531
TI  - [Effects of TIMP-2 gene transfection on biological behaviors of a metastatic
      human lung carcinoma cell line].
AB  - OBJECTIVES: To explore the suppressive effects of tissue inhibitor of
      metalloproteinase 2 (TIMP-2) on malignant phenotype of human carcinoma cells and
      to evaluate its potential application in cancer gene therapy. METHODS: A man
      malian expression vector containing TIMP-2 cDNA was constructed and transfected
      into a metastatic human lung carcinoma cell line PG. In vitro and in vivo tests
      such as Northern blotting, immunohistochemistry as well as x enografting in nude
      mice experiment were used to analyse expression levels of TIMPs and MMPs, in
      vitro and in vivo behaviors of the tumor cells before and after the gene
      transfection. RESULTS: After transfection, the TIMP-2 mRNA expression was
      upregulated significantly. Changes, in some malignant phenotypes of the
      transfectants were seen. For instance, the abilities of in vitro invasion through
      Matrigel, colony formation on soft agar, tumorigenecity as well as spontaneous
      metastasis in nude mice were remarkably decreased. Immunohistochemical staining
      and in situ hybrydization showed that MMP2, MMP9, TIMP-1 and TIMP-2 were
      expressed by both tumor cells and stromal cells, with stronger staining at the
      site of tumor invasion. CONCLUSION: Up-regulation of TIMP-2 in tumor cells could
      suppress their expression of malignant phenotype and could be used for cancer
      therapy.

PMID- 9772532
TI  - [Inhibition of angiogenesis by antitumor antibiotic C1027 and its effect on tumor
      metastasis].
AB  - OBJECTIVE: To investigate the effect of C1027, an enediyne antitumor antibiotic,
      on angiogenesis and its anti-metastatic activity. METHODS: Chick embryo
      chorioallantoic membrane assay was used for anti-angiogenesis activity and bFGF
      receptor binding assay was used for the elucidation of the possible mechanism.
      Spontaneous pulmonary metastasis of Lewis carcinoma in mice was employed to
      evaluate the anti-metastatic effect. RESULTS: C1027 was highly potent in
      suppressing angiogenesis with a minimum effective dose of 0.01 microgram/egg.
      Enediyne chromophore moiety of the C1027 molecule was essential to anti
      angiogenesis activity. Receptor binding assay showed that C1027 blocked bFGF
      binding to its receptor with an IC50 value of 2.3 x 10(-6) micrograms/ml. C1027
      markedly inhibited pulmonary metastasis of Lewis carcinoma in mice. Compared at
      equitoxic dosage level (1/4 LD50), C1027 (0.01 mg/kg, i.v., x 2) was more
      effective than mitomycin (1.25 mg/kg, i.v., x 2) and the percent inhibition of
      metastatic foci in the lung was 98% and 78%, respectively. CONCLUSIONS: C1027 is
      a new potent anti-angiogenesis agent with markedly anti-metastatic activity. The
      mechanism of C1027 suppressing angiogenesis may be related to its blocking effect
      on bFGF binding to its receptor.

PMID- 9772533
TI  - [The role of MMP-2 in the invasion and metastasis of hepatocellular carcinoma
      (HCC)].
AB  - OBJECTIVES: To get insights into the role of MMP-2 in the invasion and metastasis
      of hepatocellular carcinoma (HCC), and to find a method to judge the invasion and
      metastasis of HCC through MMP-2. METHODS: Zymograph and immunohistochemistry were
      used to study the content and types of positive cells of MMP-2 in the HCC, and
      statistical methods were used to analyse the association between the content of
      MMP-2 and the pathological indexes of HCC. RESULTS: MMP-2 was expressed by all
      the normal liver, HCC and surrounding liver parenchyma. The increase of MMP-2 and
      the presence of the active type of MMP-2 were related to the invasion and
      metastasis of HCC. The content of MMP-2 in HCC being higher than that in
      surrounding liver parenchyma was an important index to judge the invasion and
      metastasis of the HCC. The positive cells of MMP-2 found in immunohistochemistry
      were normal hepatocytes, cholangioepithelial cells, Ito cells, regenerated
      hepatocytes, new generated cholangioepithelial cells, and HCC cells. CONCLUSION:
      MMP-2 was related to the invasion and me astasis of HCC. The content of MMP-2 in
      HCC being higher than that in surrounding liver parenchyma could be bused as an
      important index to judge the invasion and metastasis of HCC.

PMID- 9772534
TI  - [The amounts of inositol 1,4,5-triphosphate and it response to epidermal growth
      factor and laminin of carcinoma substrains with high or low metastatic
      potentials].
AB  - OBJECTIVE: To examine the IP3 amounts, invasive potentials, and response to LN
      and EGF of the substrains with high or low metastatic ability from two kinds of
      carcinoma cell lines (MFC and CNZ-2Z). METHOD: Radio-ligand binding assay and
      matrigel invasive assay. RESULTS: The low metastatic substrains from the two
      lines had higher amounts of IP3 and stronger response to EGF than their
      responsive high ones, but high metastatic substrains from CNZ-2Z had stronger
      response to LN than the low ones while MFC substrains had not significant
      difference in response to LN. CONCLUSION: There is internal difference in signal
      transduction between the high and low metastatic cancer cells, and it is
      significant to study the difference in detail.

PMID- 9772535
TI  - [Quantitative analysis of E-cadherin expression and clinicopathologic evaluation
      in gastric cancer].
AB  - OBJECTIVE: To evaluate the relationship of E-cadherin (E-CD) expression to
      cellular DNA content and biological behavior of gastric cancer. METHODS: E-CD
      expression and cellular DNA content were quantitatively measured by flow
      cytometry and immunofluorescence methods in 80 cases of formalin-fixed, paraffin
      embedded gastric cancer. Systematic pathological examinations and follow up were
      performed for all cases. RESULTS: E-CD expression was significantly reduced in
      all cases of gastric cancer, fluorescence Index (FI) of E-CD expression was 0.67
      +/- 0.11 in gastric cancer, 1.0 +/- 0.07 in normal gastric mucosa (P < 0.001).
      The reduction of E-CD expression was also found in 2 cases of early gastric
      cancer. Tumors with a decrease in E-CD expression occurred significantly more
      frequently in undifferentiated, diffuse growth pattern Borrmann 4 type, positive
      lymph node (LN) metastasis and infiltrated serosa type gastric cancer, of which
      survival time was within 5 years (P < 0.001). E-CD expression was also reduced in
      gastric cancer with the number of LN metastasis above 5, metastasis to more than
      group 2. E-CD expression was lower in uneuploid cancer than that in diploid
      cancer (P < 0.01). The value of DI and PI with negative E-CD expression was
      significantly higher than that of positive E-CD expression (P < 0.01).
      CONCLUSION: Down-regulation of E-CD expression correlates with bad biological
      behavior and poor prognosis of gastric cancer. The reduction of E-CD expression
      may take place during early time of gastric cancer. Quantitative analysis of E-CD
      expression may have some value in evaluating the intensity of LN metastasis of
      gastric cancer.

PMID- 9772536
TI  - [Effects of glycated protein on the expression of plasminogen activator inhibitor
      1 of cultured human mesangial cells].
AB  - OBJECTIVE: To investigate whether nonenzymatic glycated end products (AGEs) have
      effects on the expression and bioactivity of plasminogen activator inhibitor-1
      (PAI-1), one of the seripin proteinases, which lead to extracellular matrix (ECM)
      degradation in cultured human mesangial cells. METHODS: Human mesangial cells
      (HMC) were cultured. Cell proliferation, fibronectin production, mRNA expression
      and bioactivity of PAI-1 were determined after exposure to AGE-BSA for 24 hours
      and 48 hours in vitro. RESULTS: HMC stimulated by AGE-BSA exhibited inhibition in
      HMC proliferation, increase in fibronectin production, and PAI-1 bioactivity.
      These changes were pronounced with prolongation of experimental time. PAI-1 mRNA
      expression increased significantly at 24 hr (0.45% +/- 0.06% vs 0.65% +/- 0.08%,
      P < 0.05), however more marked increase of PAI-1 mRNA expression at 48 hr (0.51
      +/- 0.08% vs 0.92 +/- 0.10%, P < 0.01). CONCLUSIONS: Increase of mRNA expression
      and bioactivity of PAI-1 induced by AGEs decreased ECM degradation and play an
      important role in the pathogenesis of ECM accumulation and glomerulosclerosis.

PMID- 9772537
TI  - [Elimination of cholesterol in human endothelial cells].
AB  - OBJECTIVE: To investigate what role the endothelial cell interfacing with blood
      components to play in cholesterol metabolism. METHODS: Isotopelabeling technique,
      Gas Chromatography/Mass Spectrometry and Western blotting were used to measure
      the presence of 27-oxygenated cholesterol in medium and the presence of sterol 27
      hydroxylase in endothelium. RESULTS: When human endothelial cells were cultured
      in a medium containing fetal calf serum, there was a significant accumulation of
      27-hydroxycholesterol and 3 beta-hydroxy-5-cholesteneic acid, products of
      cholesterol metabolism, in the medium. The rate of formation of these products
      almost increased linearly with time of cultivation. After addition of 100
      micrograms of extraneous cholesterol to the medium, the accumulation of 27
      hydroxy-cholesterol and 3 beta-hydroxy-5-cholesteneic acid increased
      significantly. Addition of more cholesterol did not further increase the
      formation of 27-hydroxy-cholesterol and caused a decrease in the formation of 3
      beta-hydroxy-5 cholesteneic acid. The presence of sterol-27-hydroxylase in the
      endothelium was demonstrated by Western blotting. CONCLUSION: Cultured human
      endothelium from umbilical veins are able to convert exogenous cholesterol into
      27-hydroxy-cholesterol and 3 beta-hydroxy-5-cholesteneic acid. Furthermore, the
      cells are able to transport these products from the cells into the medium.

PMID- 9772538
TI  - [Expression of mitogen-activated protein kinase in hypertrophic myocardium in
      SHRsp].
AB  - OBJECTIVE: To explore whether myocardial mitogen-activated protein kinase (MAPK)
      play an important role in hypertensive cardiac remodeling. METHODS: We compared
      myocardial MAPK activity by phosphocellular method and its localization and
      distribution by immunohistology in hypertrophic myocardium in SHRsp at age of 34
      weeks (34 w group) and 54 weeks (54 w group) with age matched WKY served as
      control. RESULTS: SHRsp was compared with WKY. The heart weight to body weight
      ratio was significantly increased in both groups. Myocardial MAPK activity
      increased 1.81 fold in the 34 w group and 1.46 fold in the 54 w group. MAPK
      expressed abundantly in hypertrophic myocardium, mainly localized in interstitial
      cells. CONCLUSION: MAPK might be a major pathway of transducing hypertrophic
      signals.

PMID- 9772539
TI  - [Behaviour after transplantation of brain cells into monkey models of Parkinson's
      disease].
AB  - OBJECTIVE: To observe the improved degree of pathogenic behaviour in monkey
      models of Parkinson's disease after transplantation of substantia nigra cells of
      human fetus. METHOD: 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used
      to prepare monkey models of hemiparkinson's disease, i.e., early substantia nigra
      cells of human fetus were stereotaxically transplanted into PD monkey's behaviour
      for six months, using immuno-electromicroscopy to prove the transplanted survived
      neuron. RESULTS: After transplantation, the model monkey's motion slow and muscle
      hypertonia was apparently improved. Limb tremor almost disappeared, Right
      spontaneous rotation behavior relieved. Rotating frequency caused by APO became
      less than before transplanytation, and its effect could last a year. Under the
      immunoelectromicroscope, we observed that transplanted tyrosine hydroxylase
      positive neuron was connected with the host brain cells in synapse. CONCLUSION:
      Substantia nigra neuron transplanted into the PD monkey brain can establish
      synaptic connection with the host nervous cells. Pathogenic symptoms are improved
      and the effect may remain for a longer time.

PMID- 9772540
TI  - [Platelet calcium oscillation by laser scanning confocal microscopy].
AB  - OBJECTIVE: To observe platelet calcium oscillation and the influence of
      extracellular Ca2+ on it. METHODS: We observed a single platelet intracellular
      Ca++ change and the influence of extracellular Ca2+ on it by laser sanning
      confocal microscopy when various agonists of different concentrations stimulated
      platelets. RESULTS: The other agonists except thrombin induced platelet calcium
      oscillation. With increasing agonis concentrations, the frequence of calcium
      oscillation enhanced and calcium oscillation sustained longer. In the absence of
      Ca++, the amplitude of ADP-induced calcium oscillation was smaller without
      frequence variations, and 5-TH induced calcium oscillation was inhibited.
      CONCLUSIONS: Platelet calcium oscillation increased from fluctuation either in
      the entry of external calcium or the release from internal stores.

PMID- 9772541
TI  - [The decrease of gastric mucosal blood flow in obstructive jaundice under
      stress].
AB  - OBJECTIVE: To investigate the cause of decrease of gastric mucosal blood flow
      (GMBF) in obstructive jaundice under stress. METHODS: With common bile duct
      ligation (CBDL) in Wistar rats under cold restraint stress, GMBF and the content
      of Endothelin-1, Angiotensin-II, H2, alpha 1 receptor in gastric mucosa were
      measured. Before stress anti-ET-1 serum, Enalapril, Cimentidine and Phetolamins
      were administrated, and the change of GMBF was studied. RESULTS: GMBF was
      significantly decreased in CBDL in stress than those in control subjects. The
      content of ET1 and Ang-II was significantly increaced, the density of H2 and
      alpha 1 receptor was significantly decreased. Before stress antagonist was
      administrated, and GMBF was significantly increased. CONCLUSION: GMBF was
      decreased by increased ET, Ang-II and decreased H2, alpha 1 receptor in CBDL,
      under stress. Antagonist improved gastric mucosal blood flow. They had protection
      from gastric mucosa.

PMID- 9772542
TI  - [The renal function protection of prostaglandin E1 from hemolysis caused by
      cardiopulmonary bypass].
AB  - OBJECTIVE: To observe the renal function protection of PGE1 from hemolysis caused
      by CPB during and after CPB. METHOD: F-Hb in blood, NAG & beta 2-MG in urine were
      measured in twenty patients who underwent valvular replacement operation. The
      patients were divided into two groups at random. The PGE1 group was administered
      of PGE1 with the dose of 100 ng/kg.min for 30' before CPB, 30 ng/kg.min during
      CPB intravenation and 100 ng/ml before CPB in CPB mechanical equipment. The
      control group was administered of N. S. RESULTS: After termination of CPB, F-Hb
      rose continuously, showing that the damaging RBC factors did not stop working at
      once after CPB. F-Hb and beta 2-MG were positively correlated and F-Hb and NAG/Cr
      were positively correlated, demonstrating that increased F-Hb is an important
      factor for renal function damage. At 60 minutes after CPB and 120 minutes after
      CPB, F-Hb values of PGE1 group were significantly lower than those of the control
      group. beta 2-MG and NAG/Cr of the PGE1 group also showed the same trend. The
      peak of the control group F-Hb was later than that of the PGE1 group.
      CONCLUSIONS: The results demonstrate that PGE1 can protect renal function by
      decreasing F-Hb level during CPB and shortening the time of hemolysis after CPB.

PMID- 9772543
TI  - [Relation between AIDS, spleen and splenectomy].

PMID- 9772544
TI  - [Progresses in the study of cardiovascular diseases in China, 1997].

PMID- 9772545
TI  - [Progresses in the study of respiratory diseases in China, 1997].

PMID- 9772546
TI  - [Progresses in the study of nephrology in China, 1997].

PMID- 9772547
TI  - [Progresses in the study of gastroenterology in China, 1997].

PMID- 9772548
TI  - [Progresses in the study of hematology in China, 1997].

PMID- 9772549
TI  - [Progresses in the study of rheumatology in China, 1997].

PMID- 9772550
TI  - [Progress in the study of communicable diseases in China, 1997].

PMID- 9772552
TI  - [Progresses in the study of neurology in China, 1997].

PMID- 9772551
TI  - [Progresses in the study of diabetology in China, 1997].

PMID- 9772553
TI  - [Progresses in the study of pediatrics].

PMID- 9772555
TI  - [Progresses in the study of tropical diseases and parasitology in China, 1997].

PMID- 9772554
TI  - [Progress in the study of gerontology in China, 1997].

PMID- 9772556
TI  - [Progresses in the study of general surgery in China, 1997].

PMID- 9772557
TI  - [Progresses in the study of orthopedics in China, 1997].

PMID- 9772558
TI  - [Progresses in the study of thoracic surgery in China, 1997].

PMID- 9772559
TI  - [Progresses in the study of burn surgery in China, 1997].

PMID- 9772560
TI  - [Progresses in the study of microsurgery in China, 1997].

PMID- 9772561
TI  - [Progresses in the study of urologic surgery in China, 1997].

PMID- 9772562
TI  - [Progresses in the study of pediatric surgery in China, 1997].

PMID- 9772563
TI  - [Progresses in the study of organ transplantation in China, 1997].

PMID- 9772564
TI  - [Progresses in the study of otorhinolaryngology in China, 1997].

PMID- 9772565
TI  - [Progresses in the study of stomatology in China, 1997].

PMID- 9772567
TI  - [Progresses in the study of gynecology in China, 1997].

PMID- 9772566
TI  - [Progresses in the study of anesthesiology in China, 1997].

PMID- 9772568
TI  - [Progresses in the study of perinatology in China, 1997].

PMID- 9772569
TI  - [Progresses in the study of psychiatry in China, 1997].

PMID- 9772570
TI  - [Progresses in the study of radiology in China, 1997].

PMID- 9772571
TI  - [Progresses in the study of ultrasonics in China, 1997].

PMID- 9772573
TI  - [Progresses in the study of clinical epidemiology in China, 1997].

PMID- 9772572
TI  - [Progresses in the study of nuclear medicine in China, 1997].

PMID- 9772574
TI  - [Progress in the study of endemic diseases in China, 1997].

PMID- 9772575
TI  - [Progresses in the study of laboratory medicine in China, 1997].

PMID- 9772576
TI  - [Progresses in the study of genetics in China, 1997].

PMID- 9772577
TI  - [Progresses in the study of physiopathology in China, 1997].

PMID- 9772578
TI  - [Progresses in the study of microcirculation in China, 1997].

PMID- 9772579
TI  - [Progresses in the study of pathology in China, 1997].

PMID- 9772580
TI  - [Progresses in the study of child health in China, 1997].

PMID- 9772581
TI  - [Progresses in the study of dermatology and venereology in China, 1997].

PMID- 9772582
TI  - [Surgical treatment of extrahepatic bile duct carcinoma].
AB  - OBJECTIVE: To evaluate the experience in the diagnosis and surgical treatment of
      the extrahepatic bile duct carcinomas. METHODS: 242 patients with extrahepatic
      bile duct carcinoma over the past 20 years was retrospectively studied. RESULTS:
      The origin points were carcinomas of the upper bile duct in 168, of the middle
      bile duct in 18, and of the lower bile duct in 56 patients. The preoperative
      diagnostic rates for the location and the nature of the lesion were respectively
      raised to 97.2% and 94.5% by combination of ultrasonography and CT. The curative
      resection rates for the tumors in the upper, middle, and lower bile duct over the
      recent five years reached to 50.0%, 50.0% and 71.4%. respectively. Follow-up of
      patients with curative resection showed a one year recurrent rate of 73.9% and a
      three year recurrent rate of 100.0% with a mean recurrent time of 9.6 months in
      patients with local metastasis, in contrast to 13.3%, 71.4% and 17.5 months in
      those without metastasis. Metastasis was mainly responsible for the recurrence.
      Liver or multiple organ failure, intra-abdominal infection and gastrointestinal
      hemorrhage were the common and serious complications. CONCLUSION: The case number
      of the bile duct carcinoma presented a remarkable increment tendency.
      Ultrasonography and CT were satisfactory enough for diagnosis. To reduce the
      recurrent rate, resection of the tumor together with the lymph, nervous, fatty
      and connective tissues in the hepatic hilus, even the right celiac ganglia,
      should be considered the necessary procedure. Monitoring and protecting the main
      organs to prevent the multiple organ failure, controlling the gastrointestinal
      hemorrhage and the intra-abdominal infection are important to decreasing the
      mortality.

PMID- 9772583
TI  - [Personal opinion on the break-through of traditional Chinese medicine research].

PMID- 9772584
TI  - [Clinical and experimental studies on preventing and treating anaphylactic asthma
      with Zusanli point immunotherapy].
AB  - We have studied on preventing and treating anaphylactic asthma with Zusanli (S36)
      point immunotherapy (ZPIT). Sixty-nine patients were observed. The results showed
      that the clinical curative effect of ZPIT was not only much higher than that of
      conventional desensitization therapy, but also the patients' total IgE level was
      reduced, anti-acarid IgE was lowered, SIgA level was raised, the absolute
      eosinophilic granulocyte level dropped and pulmonary function recovered. Animal
      experiment results showed that the ZPIT could more effectively suppress the
      guinea pigs' anaphylactic asthma allergized by albumin and more obviously resist
      the guinea pigs' bronchial spasm induced by histamine and acetylcholine than the
      conventional desensitization therapy and injected normal saline. The
      immunomodulating action of the ZPIT are elucidated from clinical study and animal
      experiment in the paper.

PMID- 9772585
TI  - [A study on combination therapy of Western and traditional Chinese medicine of
      acute viral myocarditis].
AB  - To investigate the combination therapy of Western and traditional Chinese
      medicine on treatment of acute viral myocarditis, 48 patients were randomly
      divided into 2 groups. The 1st group consisted of 30 patients, receiving the
      combination therapy of Western and traditional Chinese medicine, including
      Astragalus membranaceus, taurine, coenzyme Q10 and antiarrhythmics, while the 2nd
      group consisted of 18 patients, receiving the conventional therapy, including
      glucose-insulin-potassium (GIK), coenzyme Q10 and also antiarrhythmics. RESULTS:
      The efficacy of combination therapy of western and traditional Chinese medicine
      was better than that of conventional therapy in improving the clinical
      manifestation, negative converting positive EVsRNA in peripheral leukocytes and
      controlling the premature beats. CONCLUSION: The combination therapy of western
      and traditional Chinese medicine was an effective method in treating acute viral
      myocarditis.

PMID- 9772586
TI  - [Clinical observation of shexiang baoxinwan for treatment of coronary heart
      disease with angina pectoris].
AB  - Two hundred and ten patients with angina pectoris in coronary heart disease were
      randomly assigned to receiving Shexiang Baoxinwan (SXBXW), the protecting heart
      musk pills (110 patients), or receiving isosorbide dinitrate (100 patients) for 2
      weeks. They were well matched for age, anginal types, complications and cardiac
      functional grading. The results demonstrated that both agents not only could
      reduce significantly the frequencies of anginal episodes and the consumption
      amount of nitroglycerin per day, they also could result in significant
      improvement of the sigma ST segment depression in electrocardiogram. Furthermore,
      the SXBXW had better efficacy than that of isosorbide dinitrate in the total
      improvement rate of symptoms of angina pectoris and of ECG, and in the reduction
      of incidence of headache, i.e. 90.0% vs. 76.0%; 58.6% vs. 40.8%; 0.9% vs. 17%,
      respectively (P < 0.05 or P < 0.01). In addition, the onset of action of both
      agents was rapid, within five minutes (83.4% in patients using SXBXW vs. 86.3% in
      control group, P > 0.05).

PMID- 9772587
TI  - [Clinical and experimental study of shengxue syrup in treating chronic aplastic
      anemia].
AB  - The Shengxue Syrup (SXS) composed of Chinese medicinal herbs for invigorating the
      function of Spleen and resplenishing the Kidney was used in treating 115 chronic
      aplastic anemia patients. The SXS group consisted of 67 patients. After the
      median 20 months treatment the total effective rate (TER) was 97.0%. The other
      group was SXS + testosterone group consisted of 48 patients. After median 17.5
      month treatment the TER was 95.8%. The difference of TER between two groups was
      insignificant. The result of animal experiment showed that SXS could markedly
      enhance the hematopoietic stem cells as well as progenitor cells proliferation of
      bone marrow in mice.

PMID- 9772588
TI  - [Effect of beneficial mixture for body immune function on serum acute phase
      reaction protein levels in acute traumatic patients].
AB  - The levels of acute phase reaction protein (ARP)--haptoglobin (HP), plasma
      albumin (Palb), transferrin (TF) and alpha-acid glycoprotein (alpha-AG), and the
      effect of Beneficial Mixture for Body Immune Function (BMBIF), were studied in 20
      cases with acute injury. The results were shown that the metabolism of the
      protein of traumatic body was in disorder: the levels of HP and alpha-AG
      significantly increased, while the levels of Palb and TF obviously decreased.
      After the treatment of BMBIF, the ARP recovered to a certain extent. This proved
      that BMBIF could adjust the disorder of ARP metabolism.

PMID- 9772590
TI  - [Effects of ligustrazine on hemodynamics in chronic pulmonary heart disease
      patients].

PMID- 9772589
TI  - [Comparison between two diagnostic methods of computer's mathematic model and
      clinical diagnosis on TCM syndromes of rheumatoid arthritis].
AB  - Based on the test result of 14 trace elements in hair of 163 cases of rheumatoid
      arthritis, we used one of the methods of the computer's mathematic model, DYNAMIC
      to assign the patients to five groups among multidimensional space. Then, another
      method, M-DEC was used to diagnose it back on one plane. The result was compared
      with that by the usual clinical diagnosis, also five groups were obtained, the
      group of Deficiency of both Liver and Kidney, syndrome of intermingled Cold with
      Heat, Deficiency of Qi and Yin, syndrome of Dampness-Heat stagnating in
      collaterals and syndrome of Phlegm-Dampness stagnating in collaterals. And Kappa
      was 0.77, greater than 0.6. It displayed the consistency in observation of these
      two methods, which was shown reliable. After that, we have detected the
      sensitivity of the syndrome diagnosis by computer's mathematic model method, the
      result was 96.67% and the specificity of that was 95.15%. So we consider this
      method could give us an objective judgment on TCM syndromes of rheumatoid
      arthritis.

PMID- 9772591
TI  - [Experimental study on effect of Cordyceps sinensis in ameliorating
      aminoglycoside induced nephrotoxicity].
AB  - In order to evaluate the effect of Cordyceps sinensis (CS) on aminoglycoside (AG)
      induced nephrotoxicity, gentamycin was imposed on the young and old rats with CS
      administration. The renal tubular injury was ameliorated as evidenced by less
      prominent increment of BUN, SCr, sodium excretion, urinary NAGase and less
      severity of histopathological changes as compared with control. In addition, the
      use of CS could promote an earlier recovery of renal oxygen consumption insulin
      clearance, and sodium absorption in isolated perfused kidney from CS treated
      intoxicated rat than that from control. Possible mechanisms of CS on drug-induced
      nephrotoxicity include: (1) Accelerating the regeneration of tubular cells; (2)
      Protecting the sodium pump activity of tubular cells; (3) Attenuating the tubular
      cell lysosome hyperfunction stimulated by phagocytosis of AG as well as
      decreasing the tubular cell lipoperoxidation in response to toxic injury; (4)
      Reducing the tissue Ca++ content.

PMID- 9772592
TI  - [Inhibitory effects of co-cinobufotalin oral liquor on hepatitis B in vitro].
AB  - Co-Cinobufotalin Oral Liquor (CCOL) was studied for its ability to inhibit
      hepatitis B virus DNA replication, HBsAg and HBeAg expression in a HBV
      transfected cell line (2.2.15 cell). The result showed that ID50 (the drug
      concentration that inhibits HBsAg or HBeAg secretion by 50%) was 0.08 mg/ml and
      0.07 mg/ml on HBsAg and HBeAg respectively. CD50 (the drug concentration that
      reduces cell growth by 50%) was 2.5 mg/ml. TI (therapeutic index) was 31.3 and
      35.7 respectively. The present data suggest that CCOL could exert a potent
      antiviral activity against HBV in vitro. Southern blot showed that CCOL inhibited
      HBV-DNA repication in a dose-dependent manner.

PMID- 9772594
TI  - [Progress in the researches on the treatment of opiumism].

PMID- 9772593
TI  - [On the integrated therapy of traditional and Western medicine in treating heart
      failure].

PMID- 9772595
TI  - [Clinical observation on treatment of hyperinsulinemia and hyperandrogenism
      anovulatory patient with replenishing kidney-yin drugs].
AB  - In order to investigate the effect of Chinese herbal medicine for replenishing
      Kidney-Yin in treating hyperinsulinemia and hyperandrogenism anovulatory
      syndrome, 35 patients were treated with replenishing Kidney-Yin drugs for 3
      months, basic body temperature, ultrasonic examination and blood levels of sex
      hormones were taken for monitoring the ovulation, and changes of serum insulin,
      blood sugar as well as oral glucose tolerence test were observed before and after
      treatment. Thirty-five patients showed high serum insulin and testosterone levels
      but normal dehydroepiandrosterone (DHEA) level. Twenty-nine percent of their
      luteinizing hormone/folliclestimulating hormone (LH/FSH) ratio were in normal
      range. Twenty four cases completed the regular treatment and 20 of them showed
      ovulation in the 43 menstrual cycles (59.7%). Seven of 17 (41.2%) infertile cases
      become pregnant within 6 months. After 3 months of treatment, blood sugar and
      insulin level significantly decreased but the latter was still slightly higher
      than normal level. Serum testosterone level decreased significantly and reached
      normal. Results suggested that replenishing Kidney-Yin Drugs could provide a good
      microcircumstance for ovarian follicular growth, and resulted in ovulation and
      pregnancy. The mechanism is remained to be further explored.

PMID- 9772596
TI  - [Clinical and experimental studies on treatment postoperative gastric cancer with
      combined therapy of fuzhen huoxue anticancer prescription and chemotherapy].
AB  - Fuzheng Huoxue Anticancer prescription (FZHXAC) showed better clinical effect in
      treating 35 cases of postoperative patients with gastric cancer in middle or late
      stage as compared with 35 cases of controls. After treatment, the immune function
      of T-lymphocytes enhanced significantly, the hypercoagulability improved, the
      criteria such as OKT4/OKT8 ratio, antithrombase III (AT-III), fibrinolytic
      activity, etc were all normalized, the one year, 3 year and 5 year suvival rate
      of patient were elevated. FZHXAC showed obvious inhibitory action on tumor growth
      in nude mice with transplanted human gastric cancer, as compared with control,
      the difference was significant, P < 0.001. In comparing with chemotherapeutic
      drug 5-fluorouracil, FZHXAC showed no significant toxicity, it didn't influence
      the normal growth of body weight. These results suggested that FZHXAC could not
      only replenish the Zheng-Qi, improve blood circulation, improve immune function
      and extend the survival period of patient, but also might have direct inhibiting,
      killing action on gastric tumor cells, this problem is expecting for further
      research.

PMID- 9772597
TI  - [Clinical observation on aplastic anemia treated with Chinese herbal medicine
      combined with cord blood infusion].
AB  - Forty-eight cases of aplastic anemia (AA) were divided into two groups: the
      treated group (30 cases) were treated with Chinese herbal medicine and cord blood
      infusion, the control group (18 cases) were treated with cord blood infusion
      solely. The total effective rate in the treated group and the control group was
      93.3% and 72.2% respectively, the difference between two groups was significant
      (P < 0.05). Cultures of bone marrow granulocyte-macrophage colony forming units
      (CFU-GM) in vitro were measured also in both groups. Results showed that 3 months
      after treatment, the elevation of CFU-GM in the two groups were similar to each
      other, but after 6 months' treatment, level of CFU-GM in treated group elevated
      persistently and steadily, while in control group, it decreased slightly as
      compared with level at 3 months' treatment, suggesting the recovery of bone
      marrow hematopoiesis of treated group was more stable than that of control group.
      This study indicated that combined treatment of Chinese herbal medicine and cord
      blood infusion is an effective method in treating AA.

PMID- 9772598
TI  - [Clinical study in epidural injection with lappaconitine compound for post
      operative analgesia].
AB  - In this study, the effect and side-effect of epidural injection with
      lappaconitine compound for post-operative analgesia was observed. One hundred and
      twenty patients were randomly divided into 4 groups. Lappaconitine compound (LB)
      consisted of 12 mg of lappaconitine and 22.5 mg of bupivacaine, was given to
      group A (the group of observation), and lappaconitine 12 mg, bupivacaine 22.5 mg
      and morphine 2 mg to group B, C and D respectively for control. All were given by
      epidural injection with single blind method during post-operative pain of
      incision operation. Result showed that the initiating of analgesia was quicker in
      group A and C than that in group B and D, and the efficacy was group D > A > C >
      B. There was significant difference between group A and B in the above two
      parameters, P < 0.01 and P < 0.05. The analgisia maintenence time of single
      injection was D > A > B > C, that of group D was significantly longer than that
      of group A (P < 0.01). It indicated that the epidural injection with LB was more
      rapid and potent than that with lappaconitine alone in post-operative analgesia,
      and the former had no side-effect, it was safer than morphine.

PMID- 9772599
TI  - [Clinical study on treating asthma of cold type with wenyang tongluo mixture].
AB  - Sixty-eight asthma patients of Cold type were randomly divided into two groups,
      34 for each group. The treated group was treated with Chinese herbal medicine
      Wenyang Tongluo Mixture (WYTLM), the control group was treated with Salbutamol
      orally and beclomethasone dipropionate aerosol. After 8 weeks of treatment, the
      results showed that there was no significant difference between the short-term
      total effective rate of the two groups (P > 0.05). Results of followup 1 year
      after withdrawal of treatment, showed that 9 patients (26.47%) in the treated
      group and 2 (5.88%) in the control group were cured clinically, it indicated that
      the long-term curative rate of the former group was higher than that of the
      latter group significantly (P < 0.05). And the effect of treated group on
      eliminating Asthenia-Cold symptoms, improving pulmonary ventilation function,
      regulating adrenergic beta-receptors of peripheral blood lymphocyte and
      decreasing the serum level of 5-hydroxytryptamine was more superior to that of
      control group (P < 0.05-0.01). This study provided some objective basis for using
      WYTLM in preventing and treating asthma of Cold type.

PMID- 9772600
TI  - [Clinical study on effect of xinjikang capsule in reversing left ventricular
      hypertrophy].
AB  - The study was conducted on the patients suffering from left ventricular
      hypertrophy (LVH). Ninety four cases of LVH were randomly divided into treated
      group (74 cases) and control group (20 cases) treated with Xinjikang capsule
      (XJK) and Metoprolo respectively. The results showed that XJK has remarkable
      reverse effects on LVH (P < 0.01). The control group although showed some effect
      of improvement, in comparison with pretreatmental measurement the difference was
      insignificanty (P > 0.05). While in comparing the two groups, the difference of
      effect was very significant (P < 0.01). XJK could also alleviate and eliminate to
      the cause of LVH, such as improving heart function and microcirculation,
      decreasing blood viscosity, apolipoprotein, myocardial oxygen consumption,
      increasing superoxide dismutase. All these parameters measured after XJK
      treatment were significantly different from that before treatment. The difference
      of them between XJK treated group and control group was also significant (P <
      0.01 or P < 0.05). It suggested XJK capsule has reversing effect on LVH.

PMID- 9772601
TI  - [Study on the variation and mechanism of diameter of nailfold capillary and its
      blood flow speed in patient with chronic pain syndrome].
AB  - Diameter of nailfold capillaries and their blood flow speed in 90 patients with
      pain syndrome were measured accurately by using YJD clinical microcirculatory
      image analyser, and the data obtained were compared with that of 31 normal
      subjects. The results showed (1) Shortening of capillary loop and slow down of
      blood flow were revealed in patients no matter where the location of pain was;
      (2) The disturbance of microcirculation was more prominent in case of chronic
      pain patient, manifested chiefly as slow down of blood flow speed (0.19 +/- 0.09
      mm/s in afferent branch) and increase of loop diameter (15.86 +/- 6.50 microns),
      as compared with those in normal subjects (0.35 +/- 0.13 mm/s and 14.01 +/- 3.31
      microns respectively), the difference were significant, P < 0.01; (3) Typing
      according to Syndrome Differentiation of TCM, the afferent loop diameter of the
      Blood Stasis type were 9.23 +/- 1.65 microns, it was significantly different from
      that of other types; and the blood flow speed of this group was markedly slowing
      down (0.18 +/- 0.08 mm/s in afferent branch), the change was of significant
      difference in comparing with normal group, P < 0.01. Authors considered that the
      mechanism of changes in microcirculation was related to increase of blood
      viscosity and spasm or diastole of capillaries induced by neurohumoral
      regulation, and many humoral factors, as histamine, may take part in this
      procedure.

PMID- 9772602
TI  - [Clinical observation on relationship of antioxidation criteria and immune
      function of erythrocyte in patients with asthenia syndrome].
AB  - Results of observation on 31 patients of Qi-Yin Deficiency Syndrome showed that
      as compared with normal person, the superoxide dismutase (SOD) activity of
      erythrocyte in patients was lowered, the content of serum lipid peroxide (LPO)
      increased, the rosette rate of red cell C3b receptor (RC3 bRR) lowered but that
      of red cell immune complex was elevated significantly (P < 0.01). There were a
      positive correlation between erythrocyte SOD activity and RC3bRR (r = 0.381, P <
      0.05), and a negative correlation between serum LPO level and RC3bRR (r = -0.395,
      P < 0.05).

PMID- 9772603
TI  - [Effect of aconitine on content of corticotropin-releasing hormone in
      hypothalamus of rats].
AB  - The effect of aconitine on the content of corticotropin-Releasing-Hormone (CRH)
      in the hypothalamus of the normal rat injected with aconitine intraperitoneally
      was studied by means of radioimmunoassay (RIA). Aconitine is the main effective
      component of Radix Aconiti Carmichaeli Praeparata, the representative traditional
      Chinese herbal medicine of Warm-Supplementing Kidney-Yang (WSKY). Results showed
      that the content of hypothalamic CRH menifested a dosedependent increase after 7
      days intraperitoneal injection of aconitine (1 microgram/kg, 3 micrograms/kg and
      10 micrograms/kg). The CRH neurons in the paraventricular nucleus of hypothalamus
      and the neural fibers of median eminence also demonstrated increases in number
      and enrichment in gray tone as observed by immunohistochemical method of ABC.
      These results suggested that one of the possible mechanism of the WSKY drugs in
      improving the HPA axis might be exciting the hypothalamic CRH neurons.

PMID- 9772604
TI  - [Effect of shenmai injection on local defence mechanism in peritoneal dialysis
      rats].
AB  - The local defence mechanism of peritoneal cavity plays an important role in
      preventing peritonitis during peritoneal dialysis. In this experiment, the effect
      of Shenmai injection (SI) on the defence mechanism was studied in the remnant
      kidney model. The results showed that the SI which was added into dialysate could
      significantly increase the concentration of IgG, C3 in peritoneal cavity (P <
      0.05). There was insignificant change in the number of peritoneal macrophages,
      but the index and the percentage of phagocytosis had the tendency to increase (P
      > 0.05). SI also relieved the injury of peritoneal mesothelia cells. All these
      results suggested that the SI had the ability to augment the peritoneal local
      defence mechanism.

PMID- 9772605
TI  - [Experimental study on tea polyphenols in prevention of hyperlipidemia].
AB  - Hyperlipidemia (HP) was induced in quails by feeding high lipid food. Effect of
      tea polyphenol (TP) on development of HP was observed by feeding various dosage
      of TP simultaneously and was compared with that of nicotinic acid (NA). The
      results showed: (1) TP could prevent the increase of serum total cholesterol
      (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C). Effect
      of the group treated with large dose of TP was more significant than that treated
      with NA (P < 0.05). But no statistically significant difference was observed on
      the changes of TG and LDL-C between TP and NA treated group. (2) No significant
      change of HDL-C level was observed in both TP groups and NA group, but both of
      them could inhibit the elevation of atherogenic index (TC/HDL-C), their effects
      were similar. It suggested that TP might be a regulator of blood lipid.

PMID- 9772606
TI  - [Effect of osthol and total coumarins of fructus cnidii on thyroid hormone and
      thyrotropic hormone in kidney-yang deficiency rats].
AB  - Osthol and total coumarins of Fructus Cnidii were given to the model of Kidney
      Yang Deficiency rats induced by hydrocortison acetate injection, the changes of
      serum concentration of thyroxine T3, reverse T3 (rT3), T4 and thyroid stimulating
      hormone (TSH) were observed. Results showed that in comparison with normal rats,
      all of the criteria mentioned above were lowered significantly (P < 0.01) in
      model rats. After treatment, the criteria observed were all increased
      significantly (P < 0.01 or P < 0.05). It was suggested that the osthol and total
      coumarins of Fructus Cnidii could elevate the pituitary-thyroid axis function of
      Kidney-Yang Deficiency rats.

PMID- 9772608
TI  - [From the development of neck-diagnosis to space medicine].

PMID- 9772607
TI  - [Discussion on the treatment of neoplasms with activating blood to removing
      stasis].

PMID- 9772609
TI  - [Recent development in the treatment of repeated respiratory infection in child].

PMID- 9772610
TI  - [Current status of integrated traditional and Western medicine study on
      schizophrenia].

PMID- 9772611
TI  - [Clinical study of shuizhi-dahuang mixture in treating schizophrenics with blood
      stasis syndrome].
AB  - A clinical study of 67 female schizophrenics was conducted. Thirty two patients
      of them treated with the Shuizhi (leech)-Dahuang (rhubarb) mixture mainly with
      low dosage of antipsychotic drugs (combined therapy group), while other 35 cases
      were treated with antipsychotic drugs only (control group). The result showed
      that their overall therapeutic effects were similar and the combined therapy
      group could reduce the dosages of antipsychotic drugs and its side effects, and
      tended to normalize the hemorheologic indices.

PMID- 9772612
TI  - [Clinical study on niaodujing in treating chronic renal failure].
AB  - One hundred and five chronic renal failure patients were divided randomly into
      two groups, 75 cases of Niaodujing (NDJ) treatment group and 30 cases of control
      group treated with aldehyde coated oxystarch. The effects were compared between
      two groups and within the same group before and after the entry. Results
      indicated that the total effective rate and markely effecive rate of NDJ group
      (74.1% and 44.0%) were better than those of the control group (56.6% and 23.3%)
      respectively (P < 0.05). The serum creatinine, blood urea nitrogen and middle
      molecular substance were decreased and creatinine clearance rate was increased
      significantly after NDJ treatment as compared with before treatment (P < 0.05
      0.01). In comparison of two groups, the decrement of creatinine clearance rate
      and middle molecular substance and the increment of creatinine in NDJ group were
      higher than that in control group (P < 0.05-0.01). NDJ was especially effective
      in patients with azotemia or early renal failure.

PMID- 9772613
TI  - [Clinical study on combined treatment of shuizhi tuyuan powder and nifedipine in
      treating hypertension patients complicated with left ventricular hypertrophy].
AB  - Patients with essential hypertension complicated with left ventricular
      hypertrophy (LVH) confirmed by ultrasonic cardiography were divided randomly into
      observation group and control group. Both groups were treated with nifedipine.
      Shuizhi Tuyuan Powder (SZTYP, consisted of Hirudo nipponia and Eupolyphaga
      sinensis) was given in addition to the observation group. The therapeutic course
      for the two groups were 6 months. Results showed that after one course of
      treatment, the myocardial weight index lowered from 136.8 +/- 7.5 g/m2 to 130.5
      +/- 6.4 g/m2 in observation group, while in control group, it lowered from 136.7
      +/- 7.4 g/m2 to 134.3 +/- 6.2 g/m2, the difference between the two groups was
      significant (P < 0.01). The symptoms were relieved in part of the patients with
      early stage of cerebrovascular disease treated with SZTYP. The results suggested
      that SZTYP combined with nifedipine has active curative effect on essential
      hypertension patients complicated by LVH and part patients in early stage of
      cerebrovascular disease.

PMID- 9772614
TI  - [Clinical observation on fumigation and inhalation of huayin powder in treating
      psoriasis].
AB  - Thirty-nine psoriasis (PS) cases were treated by using fumigation and inhalation
      of Huayin Powder, it's effect was observed and comparison with composite
      Qingdaiwan group 34 cases was made. The result, showed that the efficacy overall
      was 94.90% in the treatment group, and 61.80% in the control (P < 0.01);
      recurrence rate and side effects of treatment group were obviously lower than
      those in the control; the medium molecular substance (MMS) content of treated
      group was higher than that of control (P < 0.01); and significantly lower in the
      treated group before treatment in comparison with that after treatment (P < 0.05)
      as well as lower than that of control. Before treatment there was insignificant
      difference in circulatory immune complex(CIC) between the treatment and control
      group (P < 0.05); however, after Huayin Powder was given, the CIC of treated
      group was significantly lower than that of before, treatment (P < 0.01). It
      indicated that both Huayin powder and composite Qingdaiwan were effective in
      treating PS, but the former being obviously better than the latter.

PMID- 9772615
TI  - [Clinical and experimental study on bushen cong-er tablet in treating
      sensorineural hearing loss].
AB  - According to the "Kidney has its orfice in the ear" in TCM theory, the authors
      adopted Bushen Cong-er tablet, a TCM preparation with the treating principles of
      the Kidney reinforcing and blood circulation promoting to remove stasis as well
      as to open up the apertures in treating 310 cases of sensorineural hearing loss.
      The results showed that therapeutical effect was satisfactory. The total effectve
      rate was 71.9%. Animal experiment also demonstrate the drug could prevent and
      cure the aminoglycoside antibiotic ototoxic hearing loss, could adjust the
      cochlear cyclic neucleotides as well as its SOD level and reduce the LPO level,
      raise the thyroid function and the function of sexual gland.

PMID- 9772616
TI  - [Clinical and experimental observation of xilixin granule combined with
      radiotherapy in treating malignant-tumors].
AB  - Thirty six patients of pulmonary or nasopharyngeal carcinoma were treated with
      Xilixin granule (XLXG) combined with radiotherapy and compared their efficacy
      with that of 31 patients treated by Zhenqi Fuzheng granule combined with
      radiotherapy for control. Results showed that the symptoms of Yin Deficiency
      syndrome in treated group were obviously improved, the leucocyte decreased by
      5.6%, while in control group it reached 25.8%, the 3 year survival rate was
      significantly higher in treated group (75.0%) than that in control group (51.6%).
      Animal experiment revealed that XLXG had the effects of tumor inhibition, it
      could increase white blood cells, platelets and hemoglobin of patients,
      especially in using large dosage. These results suggested that XLXG have some
      protective effect against radiotherapeutic damage in patients with malignant
      tumor.

PMID- 9772618
TI  - [Effect of refined xuefu capsule on mRNA expression of nitric oxide synthase of
      hypoxic ischemic myocytes evaluated by northern blotting].
AB  - Comparative study on effect of refined Xuefu capsule, Xuefu Zhuyu capsule and
      diltiazem on mRNA expression of nitric oxide synthase (NOS) and release of LDH-L,
      CK, GOT of hypoxic hypoglycemic cultured myocytes were studied by using the serum
      pharmacological method, reverse transcriptase-polymerase chain reaction (RT-PCR)
      and Northen blotting. It was shown that the three drugs can reduce release of LDH
      L,CK,GOT of myocytes (P < 0.01), the effect of refined Xuefu capsule and
      diltiazem were obvious than that of Xuefu Zhuyu capsule in reducing LDH-L release
      and NOS mRNA expression (P < 0.01), and effect of refined Xuefu capsule was the
      strongest (P < 0.01). These findings indicated that all 3 drugs have significant
      effect in protecting myocytes which related to their effect on NO production of
      myocyte particularly the refined Xuefu capsule and diltiazem.

PMID- 9772617
TI  - [Study on experimental parameters for diagnosing ganyang huafeng syndrome of
      cerebral infarction].
AB  - One hundred patients with cerebral infarction were observed, the results showed
      that Ganyang Huafeng Syndrome (GYHFS) was the major syndrome of acute cerebral
      infarction which was accounted for 60% and Qiyin Liangxu Syndrome (QYLXS), Qixu
      Xueyu Syndrome (QXXYS) were mainly observed at convalescent stage of this disease
      which was accounted for 37.78% and 31.11% respectively. This study chose plasma
      norepinephrine (NE), epinephrne (E), thromboxane B2(TXB2), 6-keto-PGF1 alpha,
      cortisol (F) and serum triiodothyroidoglobulin (T3) as the monitoring parameters,
      and the results showed that the increase of plasma NE,F,TXB2, the decrease of
      serum T3 could be considered as the comprehensive experimental parameters for
      diagnosing GYHFS of cerebral infarction.

PMID- 9772619
TI  - [Effect of zuoguiwan on early embryonic development of mice].
AB  - Effects of Zuoguiwan (ZGW, a prescription for reinforcing Kidney Yin) on early
      embryonic development were observed by using embryonic developmental retardation
      model of mice formed by alcohol. Drug was given in three ways: add ZGW into
      cultural medium directly (group A), add the serum of mice received ZGW (group B)
      and cultured the embryo taken from ZGW treated mice (group C). The result was
      compared with that treated with Bazhen decoction (BZD, a prescription for
      supplementing Qi and blood). Results showed that the in vitro developmental rate
      of embryo from 2-cell stage to blastula stage in group B and C, which approached
      to normal control group, was higher than that in untreated model obviously. While
      in BZW group, it was higher than in normal control group only in certain stage.
      However, adding ZGW directly into culture medium didn't reveal marked effect on
      early embryonic development.

PMID- 9772620
TI  - [Effects of Peucedanum praeruptorum extractum on blood pressure, left ventricular
      hypertrophy and hemodynamic changes in left ventricular hypertrophied
      hypertensive rats].
AB  - After intragastric administration of Peucedanum praeruptorum (PPE) 0.6 g/100 g
      body weight, the blood pressure was decreased significantly in both the normal
      and the left ventricular hypertrophied hypertensive (LVH) rats. The PPE could
      still prevent the formation of the left ventricular hypertrophy in renovascular
      hypertensive rats, the ratio of weight of left ventricular over the weight of
      body was reduced markedly than that of the LVH group, and was nearly the same of
      the sham-operated group. The PPE could improve both the systolic and diastolic
      function than that of the LVH group in the isolated heart, especially, the flow
      of the coronary artery was increased significantly.

PMID- 9772622
TI  - [The holistic-medicinal approach of diagnosis and treatment of sexual transmitted
      diseases by integrated traditional and Western medicine].

PMID- 9772621
TI  - [Protective effect of reduqing injection on rabbits with acute lung injury].
AB  - Acute lung injury (ALI) of rabbits was induced by endotoxin and the effects of
      Reduqing (RDQ) injection on the following indexes were studied. The results
      showed that the arterial blood pH, PCO2, lung/body index, lung wet/dry weight
      ratio, the protein and neutrophil contents in bronchoalveolar lavage fluid
      increased significently together with arterial PO2 marked drop, which were
      consistent with lung tissue damage, while administration of RDQ simultaneously
      ameliorated these changes. It is suggested that the Chinese herbal medicine RDQ
      injection could protect rabbit from the endotoxin-induced ALI.

PMID- 9772623
TI  - [Progress in the pathogenic studies of Alzheimer's disease and its therapeutic
      approach].

PMID- 9772624
TI  - [Adjustment function of life message apparatus type SMS-03].

PMID- 9772625
TI  - [Microscopic identification of the powder of roots of genus Adenophora. I. The
      roots of Sect. Basiphyllae and Sect. Pachydiscus].
AB  - This paper deals with the microscopic characteristics of the powder of the roots
      of Genus Adenophora. Eighteen species and subspecies have been studied. The
      results show that Sect. Basiphyllae and Sect. Pachydiscus can be identified
      easily based on the amount of sclerified cork cells, and 18 species, subspecies
      and varieties can be identified according to the amount, shape and thickness of
      the walls of the sclerified cork cells, the diameter and pit of the vessels, the
      number and shape of the secretion of the laticifers, and the number of inulin
      crystals.

PMID- 9772626
TI  - [Quantitative analysis of organochlorine pesticide residues in Chinese drugs].
AB  - This paper reports the GC determination of 20 organochlorine pesticides in
      Chinese drugs Flos Ionicerae and Moluodan etc by the present method of Japan for
      determinaing pesticide residues. The results suggest that except Folium Isatidis,
      Radix Codonopsis and Sanqi Pian all accord with the for provisions pesticide
      residues in Japanese foodstuffs.

PMID- 9772627
TI  - [Effects of different processed products of radix Angelica sinensis on clearing
      out oxygen free radicals and anti-lipid peroxidation].
AB  - Different processed products of Radix Angelica Sinensis could clear out
      superoxide radical (O2.-) generated through hypoxanthinexanthine oxidase system
      and hydroxyl radical (.OH) generated through Fenton action, and inhibit lipid
      peroxidation of supernatant hepati homogenate in mice induced by free radical
      generation system. There exist significant differences among the different
      processed products.

PMID- 9772628
TI  - [Effect of processing on the content of guanfu A in radix Aconiti coreani].
AB  - Quantitative determination of guanfu A in Radix Aconiti Coreani before and after
      processing has been made by dual-wavelength TLC-scanning. The results show that
      the content of guanfu A is about 0.144% before processing, and 0.106%-0.12% after
      steam processing (n = 4), which is greatly higher than other processed products.
      The average recovery rate is 97.64% (n = 5).

PMID- 9772629
TI  - [Reasonability of extracting procedures for huiyangfanben decoction].
AB  - The reasonability of extracting procedures for traditional Chinese prescriptions
      was studied with Huiyangfanben Decoction as sample. The comparative results of
      the ingredients in extractions prepared by different procedures revealed. For the
      prescriptions with complicated ingredients, more attention should be paid to the
      ingredients and their characteristics when designing the extracting procedurs,
      and in extraction the drugs should be classified according to the interaction of
      the ingredients. More extracting solvents could be used according to the
      characteristics of the active ingredients.

PMID- 9772630
TI  - [Chemical constituents of Epimedium wanshanense S. Z. He et Guo].
AB  - Five flavonoids were isolated from Epimedium wanshanense and identified as
      sagittatoside B, anhydroicaritin-3-O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L
      rhamnopyranoside, sagittatoside A, ikarisoside B and desmethylanhydroicaritin-3-O
      alpha-L-rhamnopyranosyl-(1-->2)-alpha-L- rhamnopyranoside by means of IR, UV,
      1HNMR, 13CNMR, MS and chemical evidence. They were obtained from this plant for
      the first time.

PMID- 9772631
TI  - [Studies on sapogenins of Aesculus wilsonii Rehd].
AB  - Three sapogenins were isolated from the hydrolysate of the saponin mixture
      extracted from the seeds of Aesculus wilsonii. They were identified as 21
      angeloyl-protoaescigenin., aescigenin and protoaescigenin by physicochemical
      propertise and spectroscopic analysis.

PMID- 9772632
TI  - [GC-MS analysis of essential oils from pericarps of Illicium brevistylum A. C.
      Smith and I. jiadifengpi B.N. Chang].
AB  - The chemical constituents of essential oils from the pericarps of illicium
      brevistylum and I. Jiadifeng pi were analyzed. Sixty-six compounds have been
      identified by GC-MS, of which limonene and linalool are higher in content. The
      essential oil of I. brevistylum has been found rich in 1, 8-cineole and terpinen
      4-ol.

PMID- 9772633
TI  - [Pharmacological comparative study on baiqian and baiwei].
AB  - The decoction of Cynanchum glaucescens and the ethanol extract of C. stauntonii
      show significant antitussive and expectorant actions. The decoctions of C.
      stauntonii or C. glaucescens have antiasthmatic and anti-inflammatory effects.
      The decoction of C. atratum has some expectorant effect but no antitussive or
      antiasthmatic actions. On the other hand, the decoction of C. versicolor cannot
      relieve cough nor sputum. The results indicate that both C. atratum and C.
      versicolor cannot be used as C. glaucescens or C. stauntonii.

PMID- 9772634
TI  - [Pearl and mother-of-pearl powder in health-care].
AB  - Based on pharmacological studies in files, mice and rats, the powder of sea pearl
      (Pteria martensii), mother-of-pearl and freshwater pearl has been proved to have
      tonic, anti-aging and anti-radiative actions. The effect of the sea pearl and
      mother-of-pearl powder is higher than that of freshwater pearl powder.

PMID- 9772635
TI  - [Advances in the study on the biological characteristics of Grifola umbellata
      (Pers. ex Fr.) Pilat].

PMID- 9772637
TI  - [Determination of flavonoids in different parts of five epimedium plants].
AB  - By means of RP-HPLC, nine major flavonoids in different parts of five Epimedium
      plants incorporated in the Chinese Pharmacopoeia (1990 edn.) were analyzed. The
      result shows that the total contents of nine flavonoids in four species were
      rhizome and roots > leaves > stems. Nevertheless, in terms of composition of the
      main constituents and relative contents of the five species, the leaves are
      similar to the stems but different from the rhizome and roots. The difference may
      be reflected in their pharmaceutical effects and thus deserves attention.

PMID- 9772636
TI  - [Pharmacognostical study on the Chinese drug biejia].
AB  - The Chinese drug Biejia is taken from a variety of animals. In this paper, 3
      kinds of Biejia from different genera have been studied in their
      pharmacognostical characteristics and microproperties. A key has been complied
      based on the experimental results.

PMID- 9772638
TI  - [Interspecific difference and intraspecific variation of coumarins in Cnidium
      species].
AB  - According to the results of TLC and assay of coumarins, the interspecific
      difference of coumarins in 4 Cnidium species is obvious, and 4 chemotypes have
      been found in Cnidium monnieri.

PMID- 9772639
TI  - [Curcuma longa L. tuber yield simulation model and its application under combined
      agronomic measures for good-quality, high-yield and obvious economic results].
AB  - A design of second order orthogonal rotative regression was developed and field
      tested, and the tuber models for yield, quality and benefit were simulated and
      built. The effect of agronomic measures on the tuber yield is plant density >
      phosphorus > sowing date > nitrogen > potassium. There is a clear interrelation
      effect among agronomic measures. The results of simulation experiment have shown
      that the optimal combination of farming practices can greatly increase the tuber
      yield, quality and benefit, and is adjusted according to climate, soil, ferilizer
      or manure sources, and so on.

PMID- 9772640
TI  - [Differentiation of Corydalis yanhusuo W. T. Wang ex Z. Y. Su et C. Y. Wu and its
      application].
AB  - There are differences between the big and small leaf types of Corydalis yanhusuo.
      The big leaf type is better and yields about 10% more than the small one. By
      comparing the big leaf type in terms of leaf charactistics, inflorescence and
      flower number, we name the small leaf one as C. yanhusuo f. floribunda.

PMID- 9772641
TI  - [Kidney reinforcing and yang supporting action of cistanche deserticola Y. C. Ma
      before and after preparation].
AB  - The weights of seminal vesicle and prostate gland of castrated young rats were
      significantly increased by administration of alcoholsoluble extract from
      decoction of Cistanche deserticola. The weights of testes, seminal vesicle and
      prostate gland in mice and rats were also increased by the extract. The
      phagocytic function of intra-abdominal macrophage in mice was activated by
      decoction of Cistanche deserticola. The results showed no statistical differences
      between crude and prepared drugs. The maximum oral tolerance for mouse was 40
      g/kg.

PMID- 9772642
TI  - [Comparison of ancient and modern processing methods for fructus Psoraleae].
AB  - The contents of 3 active compounds psoralen, isopsoralen and poisonous bakuchiol
      in 5 differently processed samples of Fructus Psoraleae were analysed by GC. The
      results indicate that the content of psoralen and isoporalen in the sample
      processed by the method of "Leigong's theory of processing" are 3-4 times that in
      the salt-fried sample, while the content of poisonous bakuchiol shows a tendency
      to decrease.

PMID- 9772643
TI  - [Quantitative determination of ginsenoside Rg1 in Capsulae gansuning by TLC
      scanning].
AB  - The ginsenoside Rg1 in Capsulae Gansuning was quantitatively determined by TLC
      scanning. The sample was pretreated with a chemical method featuring simplicity
      and efficacy. The average recovery of ginsenoside Rg1 is 97.95%, RSD = 1.85% (n =
      5).

PMID- 9772644
TI  - [Flavonoids in the rhizome of Sparganum stoloniferum Buch.-Ham].
AB  - Two compounds were isolated from the rhizome of sparganum stoloniferum. Based on
      the physicochemical constants and spectral data, they were identified as
      kaempferol and 5',7,3',5-tetrahydroxy-flavanonol-3-O-beta-D-glu.

PMID- 9772645
TI  - [Chemical constituents in the bark of Illicium jadifengpi B. N. Chang].
AB  - Four compounds were isolated from the bark of illicium jadi feng pi for the first
      time. Their structures were identified as 4-epi-isopimaric acid, 8,11,13,15
      abietatetran-19-oic acid, 15-hydroxydehydroabietic acid and beta-sitosterol by
      physico-chemical constants and specral analyses.

PMID- 9772646
TI  - [Active constituents lowering blood-lipid in beeswax].
AB  - Three compounds were isolated from the active fraction Lowering blood-lipid in
      the traditional Chinese beeswax (Apis cerana or A. mellifera). They were
      identified as dotriacontanol, triacontanol and octacosanol by chemical and
      spectroscopic methods.

PMID- 9772647
TI  - [Separation and preparation of indole alkaloids in Lycorma delicatula White. by
      HPLC].
AB  - A HPLC method for separating and preparing indole alkaloids is described. HPLC
      conditions for analysis: BIO-RAD series 700 HPLC, model 700 data station, UV:
      model 1749 UV-VIS monitor, column: BIO-RAD Hi-pore RP318, 250 mm x 10 mm, mobile
      phase: 80% methanol-H2O(gradient), flow rate: 1.5 ml/min, detection wavelength:
      254 nm. On the basis of spectral (1HNMR, 13CNMR, H-H COSY, MS, DEPT) and chemical
      evidence, the structures of two compounds were elucidated as beta-yohimbine
      (yohimban-16-carboxylic acid-17-hydroxy methylester (3 alpha, 16 alpha, 17 beta))
      and ajmalicine (oxayohimban-16-carboxylic acid-16,17-didehydro-19-ethyl methyl
      ester (19 alpha)).

PMID- 9772648
TI  - [Determination of adenosine in Fritillaria bulbs by ultraviolet
      spectrophotometry].
AB  - A method for the determination of adenosine in Fritillaria bulbs was developed
      using thin layer chromatography and ultraviolet spectrophotometry. This method
      has been used in the analysis of adenosine in seven species of Fritillaria.

PMID- 9772649
TI  - [Effect of danshen injection on pulmonary thromboembolism and platelet free
      radical levels in mice].
AB  - The Danshen Injection has been proved good for decreasing platelet malonaldehyde
      (MDA) levels in pulmonary thromboembolism induced by collagen and adrenaline in
      mice, as well as increasing the activity of superoxide desmutase (SOD) in
      platelets, thus providing protection against pulmonary thromboembolism and
      inhibition of platelet aggregation.

PMID- 9772650
TI  - [Effects of the fruit of Rubus chingii Hu on hypothalamus-pituitary-sex gland
      axis in rats].
AB  - The aqueous extract of the fruit of Rubus chingii (RCH) can decrease the contents
      of LH, FSH and E2, and increase the content of LHRH secreted by thymus gland as
      well as the level of testosterone in blood.

PMID- 9772651
TI  - [Influence of gypenoside on serum lipoprotein and atherosclerosis in
      hyperlipidaemia animals].
AB  - The result of the study indicates that gypenoside (GP, i.g.) can suppress the
      rise of serum cholesterol (CHO) and triglyceride (TRIG) in hyperlipidaemia mice
      and lower the content of CHO, TRIG and LDL in hyperlipidaemia quails. The study
      also shows that GP has a protective effect on diffuse lipoidosis in liver and
      atherosclerosis in hyperlipidaemia quails, and that GP can lower the lipoprotein
      levels in hyperlipidaemia animals.

PMID- 9772652
TI  - Capacitative Ca2+ entry in HL-60 cells: tetrandrine and SK & F 96365 as probes.
AB  - Agonist-activated Ca2+ entry is important in many biological responses such as
      secretion and cell growth(1,2). In nonexcitable cells which have no voltage
      operated Ca2+ channels (VOCC), agonist-receptor interaction can trigger Ca2+
      entry across the plasmalemma via several entry pathways(1-3) (Fig 1): (A)
      channels which are intrinsic structures of the receptor (receptor-operated
      channels), (B) channels which are coupled to receptors via a G-protein (G-protein
      operated channels), (C) channels which are activated by some second messengers
      (second-messenger-operated channels), and (D) channels which open upon
      intracellular nonmitochondrial Ca2+ store depletion (Ca2+ release-activated
      channels) resulting from inositol 1, 4, 5-trisphosphate-induced Ca2+ release or
      inhibition of Ca2+ re-uptake (see next section). Ca2+ entry via the 4th type of
      channel, also known as "capacitative Ca2+ entry" (CCE)[4], has aroused much
      interest in the past decade because of its intriguing nature as retrograde
      signalling. In this brief review, we present the evidence for and the possible
      biochemical processes involved in CCE. We also discuss the use of 2 novel Ca2+
      entry blockers: tetrandrine and SK&F 96365. Emphasis will be put on the human
      leukemic HL-60 cell line, a popular cell system for intracellular Ca2+
      homeostasis studies and also a model the signal transduction of which we have
      been investigating during the past few years.

PMID- 9772653
TI  - Restorative effect of Coriolus versicolor polysaccharides against gamma
      irradiation-induced spleen injury in mice.
AB  - AIM: To study the restorative effect of Coriolus versicolor polysaccharides (CVP)
      on spleen injury induced by gamma-ray irradiation in mice. METHODS: ICR Male
      mice, 6-8 wk old, were divided at random into 3 groups: A) normal control; B)
      irradiated with 1 Gy; and C) after 1 Gy irradiation, given CVP 60 mg.kg-1 (ig)
      daily for 10 d continuously. Body weight (BW), spleen weight (SW), relative SW
      (RSW), DNA synthesis of splenocytes (DNA-SS), and relative DNA-SS were measured
      on d 5, 12, 19, 26, and 33 after irradiation. RESULTS: SW, RSW, DNA-SS, and
      relative DNA-SS decreased after irradiation. CVP enhanced the recovery of SW,
      RSW, DNA-SS, and relative DNA-SS inhibited by irradiation. CONCLUSION: CVP has
      the restorative effect against spleen injury induced by gamma-ray irradiation in
      mice.

PMID- 9772655
TI  - Pharmacokinetics of m-nifedipine in rabbits after intravenous injection.
AB  - AIM: To study the dose effects on pharmacokinetics of m-Nif. METHODS: Fifteen
      rabbits were divided into 3 groups receiving i.v. m-Nif 0.5, 1, and 2 mg.kg-1.
      Plasma levels of m-Nif were determined with HPLC method. RESULTS: The
      concentration-time data were fitted with 2-compartment model. After i.v. 1 mg.kg
      1, the parameters were: Vd = 0.37 +/- 0.10 L.kg-1, T1/2 alpha = 6.4 +/- 2.9 min,
      T1/2 beta = 84 +/- 22 min, AUC = 94 +/- 16 mg.min.L-1, Cl = 0.65 +/- 0.13 L.kg
      1.h-1. No statistically significant difference was found in Cl and T1/2 beta
      between 3 dose groups. AUC (standardized to body weight) was correlated with
      doses. CONCLUSIONS: m-Nif was distributed widely and eliminated at a fairly rapid
      rate in the rabbits. No dose-dependent pharmacokinetics was found after i.v. m
      Nif 0.5-2 mg.kg-1. m-Nifedipine, 2, 6-dimethyl-3, 5-dicarbomethoxy-4-(3'
      nitrophenyl)-1, 4-dihydropyridine (m-Nif) is a new calcium channel blocker.
      Dihydropyridine calcium channel antagonists are mainly used for the treatment of
      hypertension and angina[1]. Nifedipine is susceptible to photodegradation, but m
      Nif is stable when exposed to light. The 2 drugs have the same antihypertensive
      effect[2]. So far, no report has been found on pharmacokinetics of m-Nif. Using a
      high performance liquid chromatographic (HPLC) method, we studied the dose
      effects on the pharmacokinetics of i.v. m-Nif 0.5, 1, and 2 mg.kg-1 in conscious
      rabbits.

PMID- 9772654
TI  - Tetrandrine differentially inhibits aggregation and ATP-release of rat platelets.
AB  - AIM: To examine the effects of tetrandrine (Tet) on the aggregation and ATP
      release of rat washed platelets induced by several platelet activators. METHODS:
      Gel-filtration (Sepharose 2B) was used to isolate washed platelets from adult
      rats and the platelet aggragation and ATP-release were measured simultaneously.
      RESULTS: In the presence of Ca2+ 1 mmol.L-1, Tet 300 mumol.L-1 inhibited the
      aggregation induced by ADP (25 mumol.L-1), collagen (2.5 g.L-1), and thrombin
      (103 unit.L-1) by 62%, 60%, and 34%, respectively. It also inhibited arachidonic
      acid (1 mmol.L-1)-induced aggregation. Elevating intracellular Ca2+ concentration
      with the Ca2+ ionophore, calcimycin (30 mumol.L-1), or by blocking the
      intracellular calcium pump with cyclopiazonic acid (5 mumol.L-1) initiated
      platelet aggregation, which was also inhibited by Tet. In Ca(2+)-free medium, Tet
      still elicited an inhibitory effect on aggregation induced by ristocetin (2.5 g.L
      1). Lower concentrations of Tet (30 nmol.L-1 to 3 mumol.L-1) failed to inhibit
      the aggregation (requiring Tet 10-300 mumol.L-1), but strongly suppressed ATP
      release induced by ADP 10 mumol.L-1, both of which were measured simultaneously
      in a single sample. CONCLUSION: Tet elicits a nonselective inhibitory effect on
      platelet aggregation not solely due to its Ca2+ antagonism and may act on a final
      common pathway leading to platelet aggregation. Furthermore, Tet is a much potent
      inhibitor of the release of ATP in platelets.

PMID- 9772656
TI  - Mapping of preproenkephalin mRNA in brain of spontaneously hypertensive rats.
AB  - AIM: To detect different expression of preproenkephalin mRNA (PPE mRNA) in 16-wk
      old spontaneously hypertensive rat (SHR) and age-matched normotensive Wistar
      Kyoto rat (WKY). METHODS: Nonradioactive in situ hybridization was performed
      using digoxigenin-labeled RNA probe. RESULTS: Compared with WKY rats, PPE mRNA
      levels of 16-wk-old SHR increased in hypothalamic nuclei (> 20), amygdaloid
      nuclei (> 23), ventrolateral central gray (21.2), reticular substantia nigra
      (21.5), interpeduncular nuclei (> 21), nucleus of the solitary tract (30.7),
      rostroventrolateral reticular nucleus (29.1), gigantocellular reticular nucleus
      (23.9) and thoracic spinal cord (> 30); decreased in dorsal central gray (22.7).
      No difference was found in compact substantia nigra (22.8), dentate gyrus (26.2)
      and CA1, CA2, CA3 of hippocampus (> 25). CONCLUSION: PPE mRNA in brain regions
      involved in modulation of blood pressure may be associated with the genesis of
      spontaneous hypertension in SHR. Enkephalin, an endogenous ligand of opioid
      receptors, is important in the regulation of blood pressure (BP).
      Intracerebroventricular injection (icv) of mu agonist [D-Ala2-MePhe4-Gly5-ol]
      enkephalin (DAGO) and delta agonist [D-Ala2, D-Leu5]-enkephalin (DADLE) increased
      the BP[1]. In situ hybridization study showed preproenkephalin mRNA was localized
      in hypothalamic nuclei, hippocampus, NTS, and spinal cord[2], where the
      cardiovascular regulation took place. The icv of mu agonist morphiceptin induced
      a pressor response in SHR but hypotension in WKY rat, and delta agonist Tyr-D-Thr
      Gly-Phe-Leu-Thr (DTLET) icv decreased BP in SHR but increased BP in WKY[3].
      Compared with WKY rats, SHR had greater concentration of methionine-enkephalin
      (Met-Enk) in cortex, pons, and medulla[4], but lower Leu-Enk in suprachiasmatic
      nucleus[5]. These studies imply that opiate system is disturbed in essential
      hypertension. The aim of this study is to determine whether the biosynthetic
      activity of CNS opiates in brain is altered in case of essential hypertension.

PMID- 9772657
TI  - Puerarin inhibits tetrodotoxin-resistant sodium current in rat dorsal root
      ganglion neurons.
AB  - AIM: To test if puerarin (Pue) affects slow sodium current in dorsal root
      ganglion (DRG) neurons. METHODS: Tetrodotoxin resistant (TTXr) sodium current was
      recorded with whole cell patch clamp technique on DRG neurons of young adult
      rats. RESULTS: Pue 0.01-2 mmol.L-1 inhibited TTXr sodium current by 9.5%-83.2%.
      The inhibition was concentration-dependent and partially reversible, but was not
      use-dependent nor voltage-dependent. Pue did not affect the inactivation but
      changed the potential for half maximal conductance from -26 mV to -16 mV,
      suggesting the activation process was inhibited. CONCLUSION: Pue moderately
      inhibits TTXr sodium current of rat DRG neurons.

PMID- 9772658
TI  - Genetic polymorphism of 4'-hydroxylation of S-mephenytoin in 148 Chinese of Han
      nationality.
AB  - AIM: To study genetic polymorphism of S-mephenytoin (S-Mep) 4'-hydroxylation in
      the Chinese population of Han nationality. METHODS: The lg metabolic ratio (MR)
      and lg hydroxylation index (HI) in the urine (0-12 h) after oral administration
      with 100 mg of racemic Mep tablet were determined by HPLC method in 148
      consangeously unrelated native Chinese subjects and 21 individuals of 5 families.
      RESULTS: The lg MR and lg HI showed a bimodal distribution with an antimode of 
      1.00 and 1.50, respectively. The occurrence of poor metabolizers (PM) was 13.5%
      in the population. The pedigree analysis in 5 families indicated that deficient S
      Mep hydroxylation was an autosomal recessive trait. CONCLUSIONS: The occurrence
      of PM for S-Mep 4-hydroxylation in Chinese was higher than that of the
      Caucasians, and both genetic modes were of autosomal recessive trait.

PMID- 9772659
TI  - Prophylactic effects of taurine and diltiazem, alone or combined, on reperfusion
      arrhythmias in rats.
AB  - AIM: To study the effects of taurine (Tau) and diltiazem (Dil), alone or in
      combination, on reperfusion arrhythmias in anesthetized rats. METHODS: The
      arrhythmias were produced by coronary artery ligation for 15 min followed by
      reperfusion. Malondialdehyde (MDA) content and superoxide dismutase (SOD)
      activity were measured by thiobarbituric acid fluorescence assay and colorimetric
      determination. RESULTS: Tau 70 mg.kg-1 in combination with Dil 1 mg.kg-1 were
      more effective on prevention of the reperfusion arrhythmias than each drug alone.
      The combination of both drugs not only decreased the content of MDA, but also
      increased the activity of SOD in reperfusion myocardium. CONCLUSION: The
      inhibition of lipoperoxides formation as well as the inhibition of the calcium
      influx was involved in the anti-arrhythmic effect of both Tau and Dil.

PMID- 9772660
TI  - Potassium channel openers inhibit ATP-induced cytosolic free calcium increase in
      cultured rabbit aortic smooth muscle cells.
AB  - AIM: To study the effects of potassium channel openers (PCO) on cytosolic free
      calcium ([Ca2+]i) changes and their possible mechanisms in vascular smooth muscle
      cells (VSMC). METHODS: Cultured rabbit aortic VSMC were treated with Fura-2 AM
      2.5 mumol.L-1 at 37 degrees C for 50 min. The PCO were pinacidil (Pin),
      nicorandil (Nic), lemakalim (Lem), and RP 49356 (RP). [Ca2+]i level was measured
      by fluorospectrometer. RESULTS: [Ca2+]i increase induced by K+ 30 mmol.L-1 was
      weakly inhibited by Pin, Nic, Lem, and RP (441 +/- 23, 455 +/- 48, 451 +/- 22,
      370 +/- 31 vs 544 +/- 40 nmol.L-1, P < 0.01). ATP (0.1 mmol.L-1)-induced peak and
      sustained [Ca2+]i increase were inhibited by these agents in a concentration
      dependent manner. The effects of Pin, Lem, and RP were completely canceled (peak
      phase: 549 +/- 39, 540 +/- 30, 564 +/- 13 vs 541 +/- 39 nmol.L-1; sustained
      phase: 413 +/- 25, 364 +/- 16, 377 +/- 11 vs 380 +/- 8 nmol.L-1), but that of Nic
      was only partially blocked (peak phase: 453 +/- 31 vs 541 nmol.L-1; sustained
      phase: 348 +/- 19 vs 380 +/- 8 nmol.L-1, P < 0.01) by glibenclamide (Gli, 10
      mumol.L-1). Pretreated with the Pin, Nic, Lem, and RP (10 mumol.L-1), the peak
      [Ca2+]i elevation induced by ATP was reduced in the Ca(2+)-free solution (129 +/-
      17, 142 +/- 21, 136 +/- 14, 114 +/- 9 vs 258 +/- 32 nmol.L-1, P < 0.01).
      CONCLUSION: Pin, Nic, Lem, and RP inhibited ATP-induced [Ca2+]i increase,
      associated with decreases of both Ca2+ release from intracellular store and Ca2+
      influx from extracellular store.

PMID- 9772662
TI  - Disparate effects of captopril on hypertension and blood vessel.
AB  - AIM: To study whether the effect of captopril (Cap) on vascular structure and
      function may be seperated from its effect on blood pressure. METHODS: Captopril
      treatment (group Cap A and B, 20 and 100 mg.kg-1.d-1) was given to SHR rats
      during pregnancy, weaning, and up to 16 wk of age. Study performed at 40 wk.
      Blood pressure (BP) was measured by tail-cuff sphygmomanometer, and wall/lumen
      ratio of mesenteric artery 3rd grade branch was assessed by morphometric assay.
      Resistance vessel properties were determined by hindquarter perfusion pressure
      responses to incremental doses of phenylephrine, in the presence of N omega nitro
      L-arginine methyl ester (L-NAME) or the L-arginine, the precursor of nitric oxide
      synthesis. RESULTS: Both doses of Cap prevented hypertrophy of blood vessels to
      an extent comparable to that of the untreated WKY rats (wall/lumen ratio of
      mesenteric artery, Cap A: 0.38 +/- 0.08, Cap B: 0.29 +/- 0.05 vs WKY: 0.34 +/-
      0.11, P > 0.05, respectively). The parameters derived from hindquarter perfusion
      pressure curves in Cap treated group were almost identical to that of WKY,
      significantly different from that of untreated SHR (EC50, Cap B 4.05 +/- 2.58 vs
      SHR 1.15 +/- 0.96 mL.L-1, P < 0.01; vs WKY 5.13 +/- 1.97 mL.L-1, P > 0.05).
      Addition of L-NAME or L-arginine in the perfusate augmented or attenuated the
      vasoconstriction responses in the Cap treated group. CONCLUSION: Cap initiated
      from intrauterine period normalized the vascular structure and vasoconstrictive
      responses in SHR when BP still sustained at a higher level vs WKY.

PMID- 9772661
TI  - Effects of Arg-Gly-Asp-Ser on Ca2+ transport of myocardial sarcoplasmic reticulum
      in rat septic shock.
AB  - AIM: To study the effects of Arg-Gly-Asp-Ser (RGDS), a synthetic short peptide of
      fibrinogen degradation, on the Ca2+ transport function of cardiac sarcoplasmic
      reticulum in rat septic shock. METHODS: RGDS 5 mumol.kg-1 was injected i.v. at 4
      h and 14 h after cecal ligation and puncture (CLP) operation on rats. Highly
      purified membrane of sarcoplasmic reticulum (SR) was prepared from rat hearts.
      Assays were made of ATP-dependent Ca2+ uptake by cardiac SR and [3H] ryanodine
      binding to SR. RESULTS: The initial rate and the capacity of SR Ca2+ uptake were
      increased by 104% (P < 0.01) and 12% (P < 0.05), respectively, paralleled by an
      increase in Ca(2+)-ATPase activity and a decrease in calcium accumulation of myo-
      cardium of septic rats, whereas the Bmax and Kd values of Ca2+ activated
      [3H]ryanodine binding to SR were unaffected after RGDS administration.
      CONCLUSIONS: The results indicated that RGDS have cardioprotective effects of
      maintaining Ca2+ homeostasis of cardiac myocytes by enhancing SR Ca2+ uptake in
      rat septic shock.

PMID- 9772663
TI  - Calcium channel blockade and anti-free-radical actions of panaxatriol saponins in
      cultured myocardiocytes.
AB  - AIM: To identify the calcium channel blockade and anti-free-radical actions of
      panaxatriol saponins Re, Rf, Rg1, Rg2, Rh1, and oleanolic acid saponin Ro.
      METHODS: On ventricular myocytes of Wistar rats, single channel activities of B,
      L, and T type calcium channels were recorded with the cell-attached configuration
      of patch-clamp technic, and free radical contents were measured with electron
      spin resenance method. RESULTS: Re, Rg1, Rg2, and Rh1 shortened the open times,
      prolonged the close times, and reduced the open-state probabilities of B, L, and
      T type calcium channels; Rf shortened the open time, prolonged the close time and
      reduced the open-state probability of L type calcium channel; Ro did not
      influence the activity of calcium channels (60 mumol.L-1). Re, Rg1, Rg2, and Rh1
      antagonized the increase of free radical content induced by xanthine 0.42 mmol.L
      1-xanthine oxidase 5.3 nmol.L-1; Ro and Rf had no effect (30 mumol.L-1).
      CONCLUSION: Re, Rg1, Rg2, and Rh1 had both the calcium channel blockade and
      antifree-radical actions. Rf had blockade action on L type calcium channel.

PMID- 9772664
TI  - Effects of captopril and enalapril on intracellular Ca2+ in vascular smooth
      muscle cell.
AB  - AIM: To determine whether angiotensin-converting enzyme inhibitors can affect
      Ca2+ handling in cultured aortic smooth muscle cells (ASMC) directly. METHODS:
      Cultured ASMC derived from rat aorta were loaded with the intracellular Ca2+
      ([Ca]2+i) fluorescent indicator Fura 2-AM and digital image processing technique
      was used. RESULTS: Resting [Ca2+]i was greater in ASMC from SHR vs WKY (P <
      0.01). KCl-, norepinephrine (NE)-, and angiotensin II (Ang)-induced [Ca2+]i
      increases were enhanced in ASMC of SHR vs WKY (220 +/- 6, 212 +/- 8, and 215 +/-
      14 vs 199 +/- 6, 202 +/- 7, and 195 +/- 7 nmol.L-1, respectively). Captopril
      (Cap) and enalapril (Ena) had no inhibitory effect on KCl-, NE-, and Ang-induced
      [Ca2+]i increases in ASMC of WKY. Cap and Ena inhibited KCl-, NE-, and Ang
      increased [Ca2+]i in ASMC of SHR (210 +/- 7, 194 +/- 6, and 201 +/- 6 nmol.L-1,
      respectively). Ena and nifedipine similarly decreased KCl-, NE-, and Ang
      increased [Ca2+]i. CONCLUSION: Cap blocked KCl-, NE-, and Ang-increased ([Ca2+]i)
      via a voltage-dependent Ca2+ channel of which function and specificity was
      altered in ASMC of SHR.

PMID- 9772665
TI  - Orthogonal analysis of aggravating effects of alpha-, beta-agonists and
      leukocytes on reperfusion-induced arrhythmias and ventricular fibrillation in
      Langendorff's rat heart.
AB  - AIM: To study the effect of leukocyte (Leu), alpha-agonist (alpha-Ago), and beta
      agonist (beta-Ago) on the arrhythmias induced by ischemia and reperfusion to
      determine which of the 3 factors was the most important one in exacerbating
      arrhythmias. METHODS: Arrhythmias were induced by the reduction and subsequent
      resumption of perfused flow in Langendorff's perfused rat hearts. Ventricular
      tachycardia (VT) and ventricular fibrillation (VF) were recorded on ECG, and the
      results were orthogonally analyzed. RESULTS: When Leu was present, the incidence
      of VF induced by ischemia-reperfusion was 80%. The incidence in Leu-depleted
      hearts was 20%, alpha-Ago and beta-Ago elevated it to 60% and 100%, respectively.
      The results by orthogonal analysis demonstrated Leu or alpha-Ago+ beta-Ago
      increased VF incidence. With regard to arrhythmias, arrhythmia score was
      remarkedly increased by all of 3 factors and various combinations except beta-Ago
      + Leu. CONCLUSION: Among these 3 factors, Leu was the most important one in
      facilitating reperfusion-induced arrhythmias.

PMID- 9772667
TI  - Heterogeneity of human platelet density subpopulations in aggregation, secretion
      of ATP, and cytosolic-free calcium concentration.
AB  - AIM: To investigate thrombin (500 U.L-1)-, ADP (0.1-30 mumol.L-1)-, and 5
      hydroxytryptamine (5-HT, 3 mumol.L-1)-induced aggregation, secretion of ATP and
      cytosolic-free calcium mobilization in density subpopulations of human washed
      platelets. METHODS: Using Percoll discontinuous gradient. RESULTS: The human
      platelets were separated into high density (HD), intermediate density (ID), and
      low density (LD) subpopulations, and their sizes were diminished with decreasing
      density (r = 0.978, P < 0.01). The magnitude of aggregations by thrombin, ADP,
      and 5-HT was more significant in HD platelets than that in LD platelets (P <
      0.01). The amount of secretion of ATP induced by thrombin and ADP in HD platelets
      was also much higher than that in LD platelets (P < 0.01), except for 5-HT which
      did not cause the ensuring release reaction in any subpopulation of human
      platelets. Thrombin (1500 U.L-1)-, ADP (mumol.L-1)-, and 5-HT (3 mumol.L-1)
      induced cytosolic-free calcium mobilization was evaluated as well. Results showed
      that the resting level of cytosolic-free calcium concentration ([Ca2+]i) was the
      same in all subpopulations, about 80-90 nmol.L-1. However, the level of [Ca2+]i
      mobilization was entirely different, heightened with increasing density.
      CONCLUSION: The function of HD platelets was much stronger and more active than
      that of LD platelets in human.

PMID- 9772666
TI  - Endogenous inhibitors of nitric oxide synthesis and lipid peroxidation in
      hyperlipidemic rabbits.
AB  - AIM: To examine whether the elevation of endogenous NG, NG-dimethylarginine (DMA)
      content is related to lipid peroxidation in the high lipid-fed rabbit. METHODS:
      In high lipid diet-fed rabbits, concentrations of serum cholesterol,
      triglyceride, malondialdehyde (MDA), and DMA were measured, and endothelium
      dependent relaxation to acetylcholine (ACh) was tested. RESULTS: After 6-wk on a
      high lipid-diet, the levels of serum total cholesterol, triglyceride, MDA, and
      DMA were increased vs those in control group (MDA was 2.88 +/- s 0.20 vs 1.54 +/-
      0.13 nmol.L-1, P < 0.01 and DMA was 1.51 +/- 0.07 vs 0.75 +/- 0.13 mumol.L-1, P <
      0.01), while the endothelium-dependent vasodilation in the isolated thoracic
      aorta was impaired (the maximal response to ACh was 45.59 +/- 3.10 vs 76.93 +/-
      5.68%). Supplementation with vitamin E decreased MDA and DMA content and improved
      the endothelium-dependent vasodilation. CONCLUSIONS: An increase in serum
      concentration of DMA may be secondary to the elevation of lipid peroxides in the
      hyperlipidemic rabbit.

PMID- 9772668
TI  - Molecular modeling of mu opioid receptor and its interaction with ohmefentanyl.
AB  - AIM: To build up the structure model of mu opioid receptor, then combined with
      the receptor model, to investigate the action mechanism of ohmefentanyl on the
      receptor. METHODS: Using the three-dimensional structure of bacteriorhodopsin as
      a template, we constructed mu opioid receptor model on computer. Ohmefentanyl was
      then docked into the supposed receptor binding sites. RESULTS: A good ligand
      receptor interaction model was achieved. The possible binding sites were found to
      be Asp147 and His319. The protonated N atom of ohmefentanyl form potent
      electrostatic and hydrogen-bonding interactions with residue Asp147 of the
      receptor, the O atom of the carbonyl group form weak electrostatic and hydrogen
      bonding interactions with residue His319, and the two phenyl groups form pi-pi
      interactions with some aryl residues of the receptor around ligand. CONCLUSION:
      The ligand-receptor interaction model should be helpful for rational design of
      novel analgesic.

PMID- 9772670
TI  - Photosensitization of bilirubin on proliferation and DNA synthesis in ascitic
      hepatoma cells.
AB  - AIM: To observe the effects and its mechanism of photosensitization of bilirubin
      on ascitic hepatoma (Hep A) cells. METHODS: After the cells were illuminated
      under the light (1.0 x 10(5) lx) for 10 min, deoxy[3H]thymidine was added for DNA
      synthesis assay. The cells were dyed with 0.5% trypan blue and were counted.
      RESULTS: The cell mortality of illuminated groups were much higher than that of
      dark groups (P < 0.01). The inhibitions of DNA synthesis of illuminated groups
      were stronger than that of dark groups (P < 0.01). The cell mortality and
      inhibition of DNA synthesis of illuminated groups were positively dependent upon
      the concentrations of bilirubin and illuminating time. No difference of DNA
      synthesis between room light illumination groups and dark groups (P < 0.05).
      CONCLUSION: The photosensitization of bilirubin killed Hep A cells obviously.
      Bilirubin under room light had no effect on inhibition of DNA synthesis. The
      photosensitization of bilirubin was closely related to 1O2 and H2O2 and not to
      OH. and O2-. Bilirubin, the end product of heme catabolism in mammals, is a
      potentially cytotoxic, lipid soluble waste product that needs to be excreted.
      However, bilirubin at micromolar concentration in vitro, efficiently scavenges
      peroxyl radicals. In liposomes, bilirubin suppresses the antioxidation more than
      alpha-tocopherol, which is regarded as the best antioxidant of lipid
      peroxidation. Thus bilirubin is a physiological, chain-breaking antioxidant.
      Bilirubin exhibited antitumor activity and acted as a photosensitizer with four
      pyrrole rings. Many photosensitizers have been used to treat cancer due to their
      photosensitization. In this paper, the photosensitization of bilirubin on DNA
      synthesis in ascitic hepatoma (Hep A) cells and on cell mortality were studied.

PMID- 9772669
TI  - Effect of anisodine on acute forebrain ischemia-reperfusion damage in rats.
AB  - AIM: To study the protective effect of anisodine (Ani) on acute forebrain
      ischemia-reperfusion injury in rats. METHODS: Both vertebral arteries were
      occluded by electrocautery. Severe, but transient bilateral cerebral ischemia was
      produced by clamping both common carotid arteries in rats. Atomic absorption
      spectrophotometric and spectrophotometric methods were used to determine the
      contents of calcium and extravasated Evans blue (EB), respectively, remained in
      forebrain at 60-min recirculation after 30-min ischemia. RESULTS: At 60-min
      recirculation, the brain calcium contents were increased from 112 +/- 6
      micrograms/g brain dry weight in control (sham operation) group to 165 +/- 7
      micrograms/g brain dry weight with marked increase of EB extravasation. Ani (2.5
      mg.kg-1, i.p.), and scopolamine (Sco, 0.25 mg.kg-1, i.p.) decreased the elevated
      calcium and extravasated EB contents. CONCLUSION: Ani prevented the brain from
      ischemia insults through reducing intracellular calcium accumulation resulted
      from ischemia and reperfusion.

PMID- 9772671
TI  - Microscopic observations on livers of rabbits and dogs infected with Schistosoma
      japonicum cercariae and early treatment with artemether or praziquantel.
AB  - To study the histopathological change of the liver of the hosts treated with
      artemether (Art) or praziquantel (Pra) in early stage after infection with
      Schistosoma japonicum cercariae. METHODS: Dogs infected once with schistosome
      cercariae were treated ig with Art 10 mg.kg-1 or Art capsule (ArtC) 15 mg.kg-1 on
      d 7, or praziquantel (Pra) 30-40 mg.kg-1 on d 21 after infection, followed by the
      repeated dosing once every 1 or 2 wk for 2-4 times. In rabbits, infected with 48
      52 schistosome cercariae once every other day for 5 times, were treated ig with
      Art 10 mg.kg-1 or Pra 30 mg.kg-1 was started on d 7 or on d 21 after the first
      infection, followed by the repeated dosing every 1 or 2 wk for 2-3 times.
      RESULTS: After above mentioned dogs or rabbits were treated ig with Art, ArtC or
      Pra, the female worm reduction rates were 92.1%-100%. Histopathological
      examination showed that the reduction rates of total granuloma in the liver
      sections of the dogs and rabbits were 70.9%-97.3% and 76.5%-97.4%, respectively.
      Meantime, the structure of the hepatic lobules was normal with normal arrangement
      of the liver bundle. CONCLUSIONS: Early treatment with Art or Pra exhibited a
      promising effect of protection of the liver of the dogs and rabbits infected with
      schistosome cercariae. Early treatment of infection with schistosome cercariae
      kills the Female worms before oviposition. Thus, the host will be protected from
      the damage caused by schistosome eggs. Promising results were obtained when mice
      and rabbits received an early treatment with artemether (Art) or praziquantel
      (Pra). This work was to study the liver infected with cercariae and treated by
      intragastric gavage (ig) with Art, Art capsule (ArtC) or Pra in early stage after
      infection.

PMID- 9772672
TI  - Effects of ginsenoside Rg1 on c-fos gene expression and cAMP levels in rat
      hippocampus.
AB  - AIM: To study the mechanisms of Rg1 antiaging and nootropic function. METHODS:
      Using Northern and Western blot analyses, the levels of c-fos mRNA and fos
      protein were determined in the hippocampus of young and old rats treated with or
      without ginsenoside Rg1. RESULTS: The expression of c-fos gene and protein was
      decreased in the hippocampus of aged rats, but dose-dependently increased in
      young and aged rats after the administration of Rg1. Furthermore, Rg1 increased
      the level of cAMP in the hippocampus of both young and old rats. CONCLUSION: The
      changes at the genomic and protein levels, arisen from the increase of cAMP,
      provide an explanation of the mechanisms of Rg1 nootropic and antiaging function.
      The c-fos proto-oncogene is the prototype of the early-response class of genes.
      It encodes for a nuclear phosphoprotein, which after forming a complex with the
      protein product of another oncogene c-jun, binds to the AP-1 sites of DNA, and
      acts as a regulatory factor for gene transcription. The c-fos gene expression can
      be considered as a marker for neuronal activity. Moreover, fos protein is
      believed to be involved in processes related to neuronal plasticity. Ginsenoside
      Rg1 is one of the important pharmacological principles of ginseng and shares many
      pharmacological effects of this plant, such as, facilitating learning and memory,
      and alleviating many ailments, especially those associated with aging. Since the
      c-fos gene expression might be of crucial importance for neuronal activity and
      cAMP is a factor regulating gene expression. The present work was to study the
      effects of Rg1 on c-fos mRNA and protein expression as well as cAMP and cGMP
      levels.

PMID- 9772673
TI  - Effects of Coriolus versicolor polysaccharides on superoxide dismutase activities
      in mice.
AB  - AIM: To study if Coriolus versicolor polysaccharides (CVP) influence the
      superoxide dismutase (SOD) activities in mice. METHODS: Normal, tumor-bearing,
      and radiated ICR mice were injected ip with CVP daily for 3-15 d. The SOD
      activity was assayed by epinephrine autoxidation test. RESULTS: The SOD
      activities in lymphocytes and thymus were increased by CVP in both the normal
      mice with or without delayed hypersensitivity (DH). In tumor-bearing mice, CVP
      exerted not only inhibitory effects on tumor, growth and SOD activity in tumor
      tissue but also complete or partial restorative effects on the suppressed DH and
      on the declined SOD activities in lymphocytes, spleen, and thymus. The total SOD
      and manganese-containing SOD (MnSOD) activities in lymphocytes and thymus were
      dose-dependently enhanced by CVP (5-20 mg.kg-1) on d 3 after the tumor
      transplantation. In the mice exposed to 60Co (3 or 6 Gy), DH and SOD activities
      were dose-dependently decreased. These changes were completely or partly
      prevented by CVP. CONCLUSION: CVP exerted the favorable effects on SOD activities
      in mice. Coriolus versicolor polysaccharides (CVP) exert inhibitory effects on
      experimental and clinical tumors. These effects are presumed to be mediated
      mainly by host-defence mechanism, especially immunological responeses. Superoxide
      dismutase (SOD) plays an important role in protecting cells against superoxide
      radical (O2-.) damages and over-production of O2-. or SOD abnormities exist in
      many diseases. The present study was to investigate if the CVP could exert some
      favorable effects on SOD activities in vivo.

PMID- 9772674
TI  - Reduction of doxorubicin resistance by tetrandrine and dauricine in harringtonine
      resistant human leukemia (HL60) cells.
AB  - AIM: To study whether tetrandrine (Tet) and dauricine (Dau) can reduce
      doxorubicin (Dox) resistance in the harringtonine (Har)-resistant human leukemia
      cells. METHODS: The drug cytotoxities were determined by counting cell numbers
      and colony formation. Cell cycle phases were assayed by flow cytometry, Dox
      contents were quantified by Dox fluorescence. RESULTS: The non-cytotoxic
      concentrations of Tet and Dau potentiated the growth-inhibitory actions of Dox in
      the Har-resistant HL60 cells. The colony formation effiencies were reduced from
      60% by Dox to 0.2% by Tet + Dox and 9.2% by Dau + Dox. Retardation of the G2M
      phase cells was increased. But Tet and Dau did not potentiate Dox cytotoxities in
      the sensitive HL60 cells. Dox accumulation in the Har-resistant HL60 cells
      treated by Tet was increased. CONCLUSION: Dox resistance in the Har-resistant
      HL60 cells treated by Tet or Dau was reduced, due to the increase of Dox
      accumulation in the cells. One of the mechanisms of multidrug resistance in tumor
      cells is overexpression of cell membrane glycoproteins, termed P-glycoprotein
      (PGP). PGP pumps antitumor drugs out of tumor cells, causing drug resistance.
      Calcium antagonists and some calmodulin inhibitors such as verapamil, nifedepine,
      trifluorapine have effect on reversion of drug resistance, binding directly to
      PGP, but side effect of them is intolerable in clinical use. So searching for
      other potentiators to overcome drug resistance may be another avenue. Tetrandrine
      (Tet) effectively circumvented the resistance of Chinese hamster ovary cells to
      doxorubicin (Dox). Dauricine (Dau) is a bisbenzylisoquinoline alkaloid from
      Stephaia tetrandra. In this paper we studied whether Tet and Dau could reduce Dox
      resistance in the harringtonine (Har)-resistant human leukemia 60 (HL60) cells.

PMID- 9772675
TI  - Augmentation of TNF-alpha production, NK cell activity and IL-12 p35 mRNA
      expression by methionine enkephalin.
AB  - AIM: To study the host immune surveillance functions by the neuropeptide
      methionine enkephalin (met-enk). METHODS: To measure the effects of met-enk on NK
      activity, the production and gene expression of anti-tumor cytokines tumor
      necrosis factor alpha (TNF-alpha) and interleukin-12 (IL-12) in vitro and in
      vivo. RESULT: Met-enk promoted NK activity at 1 x 10(-8) - 1 x 10(-5) mol.L-1,
      increased TNF-alpha production both in vitro and in vivo, and enhanced IL-12 p35
      gene transcription after ip 0.1 mg.kg-1 for 6 d. CONCLUSION: The up-regulating
      effects of met-enk contribute to the host neuro-immunomodulating mechanism
      against tumors and invading antigens. Enkephalins and endorphins were originally
      described as the endogenous ligands for the morphine receptors in the brain. In
      addition to their central nervous activity, an immunomodulating action of the
      enkephalins was first reported in 1979. Methionine enkephalin (met-enk) regulated
      a variety of immunological responses, including enhancing the proliferation of
      human peripheral lymphocytes and mouse spleen cells, regulating antibody
      production, natural killer cells (NK) activity and synthesis of a number of
      cytokines. These results suggested that met-enk might be used to elevate the body
      resistance to cancer and other diseases, or diminish autoimmune responses which
      are detrimental to host. To elucidate that met-enk has the activity of anti-tumor
      through related immune regulating responses, this study is to investigate the
      effects of met-enk on immune surveillance and immune defence functions.

PMID- 9772676
TI  - [Effect of (+/-)12-chloroscoulerine on brain dopamine receptors].
AB  - AIM: To assess potencies of tetrahydroprotoberberines (THPB) and
      hydrobenzyltetrahydroisoquinolines (HBTI) on DA receptors. METHODS: The receptor
      binding assay with calf striatum to D1 and D2 receptors, and the animal behavior
      tests were used. RESULTS: (+/-) 12-Chloroscoulerine (CSL) was the most potent one
      among the THPB and HBTI. The affinities of CSL to D1 and D2 receptors were 13 and
      51 nmol.L-1, respectively. In rats, CSL showed an antagonistic effect on the
      stereotypy and induced catalepsy. In the 6-OHDA lesioned rats, however, CSL
      exerted the agonistic effect to DA receptors. CONCLUSION: CSL had dual actions to
      DA receptors and its effects were similar to that of (-)stepholidine.

PMID- 9772677
TI  - [Effects of aspirin and nifedipine alone or in combination on mesenteric
      microcirculation of rats].
AB  - AIM: To study the effects of the combination of aspirin (Asp) and nifedipine
      (Nif) on mesenteric microcirculation of rats. METHODS: Acute microcirculation
      disturbance (AMD) was produced by high molecular weight dextran (M(r) 480,000,
      360 mg.kg-1 i.v.). Arteriole and venule blood flow velocity and diameter (ABFV,
      VBFV, AD, VD) and blood flow state (BFS) were observed by intravital
      microcirculation method. RESULTS: Asp 2.5, 5 mg.kg-1, Nif 0.05, 0.1 mg.kg-1, Asp
      + Nif (1 + 0.025), (2.5 + 0.05) mg.kg-1, i.v. had the significant increase of
      11.1%, 31.3%, 18.5%, 19.3%, 30.5%, 39.8% of ABFV and 12.5%, 25.7%, 12.6%, 15.2%,
      29.6%, 36.1% of VBFV respectively, the marked improvement of BFS, and the
      distinctive increase of 4.3%, 17.9%, 35.9%, 39.7%, 15.2%, 42.8% of AD and 2.2%,
      4.2%, 26.2%, 27.4%, 3.4%, 28.9% of VD separately, and got a raise in the number
      of capillaries. Asp + Nif (1 + 0.025), 2.5 + 0.05) mg.kg-1 i.v. could reverse
      AMD. CONCLUSION: Asp was superior to Nif in the increase of BFV, but Nif was
      superior to Asp in expansion of blood vessel. Asp in combination with Nif
      produced marked synergistic action and protection againist AMD.

PMID- 9772678
TI  - [Nuclear matrix-lamina-intermediate filament system in PtK 2 cells].
AB  - Selective extraction, whole mount cell preparation and DGD embeddment-free
      section were involved in visualizing the nuclear matrix-lamina-intermediate
      filament system in PtK 2 cells. After extraction the anaphase chromosome residues
      adjoined to the cytoplasmic intermediate filament in some areas.
      Immunofluorescent staining showed us that the intermediate filament reacted with
      AE 1 and AE 3; McAb 223 could be localized specifically on the lamina while McAb
      C 23 could crossreact with cytoplasmic intermediate filament beside the lamina
      location, monoclonal antibody against lamin A (C) could also bind to chromosome
      residues. Antibody to 280 kD nuclear matrix protein which were positive stained
      in HeLa cells could not react with the nuclear matrix components of PtK 2 cells.
      2-D electrophoresis demonstrated that there were some differences in the
      composition of the nuclear matrix-lamina-intermediate filament system of HeLa and
      PtK 2 cells. TdR treatment could lead to alteration of nuclear matrix proteins.

PMID- 9772679
TI  - [Effect of inhibition of expression PCNA with ribozyme on the proliferation of
      HeLa cells].
AB  - The Proliferating Cell Nuclear Antigen (PCNA), which is an auxiliary protein for
      DNA polymerase delta, is found to be essential for cellular DNA replication. A
      designed hammerhead ribozyme, with high efficiency to cleave the PCNA mRNA site
      specificly in vitro, was constructed into a self-trimming expression plasmid, and
      then was introduced into HeLa cells by lipofectin reagent. Small molecular RNAs,
      isolated from total cellular RNA with the same length as active ribozyme, can
      cleave the target RNA in vitro, which suggested that this expression plasmid can
      yield active ribozyme molecules in cells. In comparison with the vector control,
      the entrance of S phase of the HeLa cells transfected by the ribozyme expression
      plasmid was delayed 8 hours after serum stimulation. Mean-while, those cells
      transfected by mutant inactive ribozyme as antisense RNA control was delayed only
      3 hours. These results demonstrated that this ribozyme can inhibit the DNA
      replication in HeLa cells effectively and could be used as a potential tool to
      study the function of PCNA in cellular DNA replication and cell cycle
      progression.

PMID- 9772680
TI  - [Vimentin and Nup 180 in vitro binding assay].
AB  - In order to investigate relationship between vimentin and nuclear pore complex,
      we examined binding ability of vimentin, expressed in E. coli, with nucleoporin,
      isolated from rat liver nuclei, in vitro. Negative staining electron microscopy
      showed that the vimentin expressed in bacteria assembled 10 nm filament in vitro.
      SDS-PAGE and western blotting showed that Nup 180 bind to vimentin in binding
      assay in vitro. Combining immunogold labeling and negative staining electron
      microscopy techniques, we showed that Nup 180 bind on the 10 nm vimentin
      filaments. The experiment results indicated that vimentin filament may be
      anchored on nuclear pore complex in vivo by binding with Nup 180.

PMID- 9772681
TI  - [rhTGF-beta 1 induced differentiation of human promonocytic leukemia THP-1
      cells].
AB  - With promonocytic leukemia cell line THP-1 cells as an experimental material, the
      present paper described the proliferation, differentiation and maturation of
      these cells into m phi-like cells when they were treated with rhTGF-beta 1. Both
      cell number count and 3H-TdR uptake experiments indicated that rhTGF-beta 1
      obviously inhibited the proliferation of THP-1 cells, and the inhibiting effect
      was related to its concentration. At the same time, the changes in the mode of
      cell growth and morphology occurred. The cells changed gradually from suspensive
      into adherent state and formed two groups of cell populations. The number of
      adherent cells formed was dependent on the concentration and duration of the
      treatment of rhTGF-beta 1. Therefore, based on the degree of inhibition of cell
      proliferation and the number of adherent cells with different rhTGF-beta 1
      concentrations in a trial experiment, 1.25 ng/ml rhTGF-beta 1 was chosen as the
      dose in other experiments. From scanning electronmicroscopic observation, it was
      found that the external morphology of rhTGF-beta 1 treated THP-1 cells gradually
      transformed into typical macrophage-like cells. Concomitantly, their subcellular
      organelles also became progressively matured, with primary lysosomes typical for
      early M phi in 72 h and secondary lysosomes and phagosomes for mature M phi in
      120 h of induction, as observed with transmission electron microscope. The ANAE
      activity, NBT reduction and phagocytosis of differentiated adherent cells were
      higher than those of control cells and suspensive cells. Specific anti-human TGF
      beta-neutralizing mAb could completely block the differentiation of THP-1 cells
      into M phi-like cells. To sum up, from the results of the studies on cell
      morphology, growth mode, ultrastructures, phagocytosis, enzyme activation and TGF
      beta 1 mAb blocking of induction and differentiation, it is clear that rhTGF-beta
      1 can induce THP-1 cells to differentiate and mature into M phi-like cells, with
      the parallel development of cytoplasmic organoids, phenotype variation and the
      gaining of phagocytosis activity etc. Concordantly, rhTGF-beta 1 made the M phi
      like cells to an activated state as they became matured during the induced
      differentiation.

PMID- 9772682
TI  - [Interaction of cis-regulatory element in the 5' flanking sequence of human beta
      globin gene with trans-acting factors at different developmental stages].
AB  - Human beta-globin gene mainly expressed in the adult bone marrow, while not
      expressed in fetal liver, adult liver and K562 cells. Using gel mobility shift
      assay, different protein factors binding to the regulatory elements (from -372 to
      -194 bp) in the 5' flanking sequence of human beta-globin gene were detected in
      the nuclear extracts from human fetal liver, adult liver and K562 cells
      respectively. Competitive experiments showed that both the protein factors from
      adult and K562 cells not only bind to negative control region 2 (NCR 2, from -372
      to -224 bp), but also bind to positive control region (PCR, from -223 to -194
      bp), suggesting that there may be similar mechanism to silence the expression of
      human beta-globin gene in these two kind of cells. The protein factor in human
      fetal liver only binds to NCR 2, indicating that there is a particular silencing
      mechanism for beta-globin gene expression in human fetal stage.

PMID- 9772683
TI  - [Experimental treatment of brain tumor cells using CD suicide gene].
AB  - A negative selection system for glioma gene therapy was established in vitro. C 6
      rat glioma cells were infected with recombined retrovirus which contain
      Escherichia coli cytosine deaminase (EC-CD) gene. The enzyme CD can transform the
      non-toxic prodrug 5-Fluorocytosine (5-FC) to the highly cellular toxic compound 5
      Fluorouracil (5-FU). The growth inhibition studies proved that CD-positive cells
      were highly sensitive to 5-FC, the IC50 about 3 mumol/L, compared with an IC50 of
      approximately 6000 mumol/L in parental C 6 cells. Both CD-positive and negative
      cells were sensitive to 5-FU at very low concentration (IC50 < 1 mumol/L). Mixed
      cellular assay showed CD-positive cells had "bystander effect" on CD-negative
      cells when exposed to 5-FC. Our results demonstrate that EC-CD gene should be an
      efficient suicide gene for the treatment of glioma.

PMID- 9772685
TI  - [Preliminary studies on the rabbit oviductin "DPF-1"].
AB  - Anti-rabbit 64 kDa oviductin (named Development Promoting Factor-1, DPF-1)
      antibody could inhibit totally the early development of mouse fertilised eggs
      cultured in the conditioned medium derived from the rabbit oviduct mucosa
      epithelial cells, revealed that DPF-1 synthesized and secreted from rabbit
      oviduct mucosa has a function to overcome the developmental block of early mouse
      embryos. It seems that DPF-1 consists of a group of polypeptide isoforms, since
      its isoelectric points are ranging from 7.2 to 8.1 (Fig. 3). The synthesis and
      secretion of DPF-1 was not dependent on either 17 beta-estradiol or progesterone
      (Fig. 7), it can pass through zona pellucida easily and associate tightly with
      the early embryonic cell membrane (Fig. 6). By using Western blotting method, we
      found that DPF-1 was not appeared in the tissues of liver, heart, lung, spleen,
      uterus, ovary, small intestine, skeleton muscle and brain, but in that of oviduct
      (Fig. 4): some DPF-1 homologous molecules were also revealed in the oviduct
      tissues of mouse and golden hamster, their apparent molecular weights were 32
      kDa, 72 kDa in mouse, and 49 kDa, 68 kDa in golden hamster (Fig. 5). Results
      obtained from the in vivo anti-fertility experiment, namely to analyse the anti
      fertility effect in adult female mice after active immunization with DPF-1,
      showed that the fertility decreased significantly as compared to those of
      controls (p < 0.01) (Table 1). DPF-1 and its in vivo "loss of function" evidence
      we obtained will encourage us to study the mechanism of DPF-1 in overcoming the
      developmental block of early embryos, and its role in transition from maternal to
      embryonic control of early development.

PMID- 9772684
TI  - [Cloning and identification of recombinant cDNA to a rabbit oviductin "DPF-1"].
AB  - A recombinant cDNA library to polyA + RNA isolated from rabbit oviduct epithelial
      cells was constructed, and screened with a polyclonal antibody against DPF-1 (64
      kDa). 4 immunopositive plaques (DPF-1.1, DPF-1.2, DPF-1.3 and DPF-1.4) were
      purified. The polyclonal antibodies were epitope-selected respectively against
      the fused proteins produced by these positive recombinant plaques. Identification
      of recombinant clones by epitope selection revealed that the epitope-selected
      antibodies from DPF-1.1, DPF-1.2 and DPF-1.3 could recognise not only DPF-1, but
      44 kDa protein also (Fig. 2). By using EcoRI-Not1 digestion method, the insert
      cDNA fragment size of these three recombinants was revealed to be 0.8 kb, 1.2 kb
      and 1.2 kb respectively (Fig. 3). These cDNA fragments were then isolated and
      subcloned into pBluescriptKS, and recombinant plasmids (pDPF-1.1, pDPF-1.2 and
      pDPF-1.3) were constructed (Fig. 4). Dot blot hybridization with a 32p-labeled
      1.2 Kb-insert of cDNA from pDPF-1.3 indicated that these recombinant plasmids
      could cross-hybridized (Fig. 5), further indicating that they all possessed a
      common nucleic acid sequence. Dot and Northern blotting analysis of total RNA
      prepared from eight different tissues (skeleton muscle, heart, kidney, oviduct,
      liver, spleen, lung and small intestine) showed that the gene encoding DPF-1 was
      expressed specifically in the oviduct tissue (Fig. 6, Fig. 7).

PMID- 9772686
TI  - [Study on growth and differentiation of ES cells transfected with LIF gene].
AB  - We constructed plasmids pSVLD(+) and pSVLD(-) containing human D-form Leukemia
      Inhibitory Factor (LIF) cDNA sequence in sense or antisense orientation,
      transfected them into cells of an embryonic stem cell line ES-5, and isolated 248
      pSVLD(+)-transfected and 93 pSVLD(-)-transfected G 418-resistant clones. By
      stepwise reducing LIF concentration in the medium, we obtained 3 pSVLD(+)
      transfected clones (A 1-3) that could grow in 15% BRL-CM, including ESL(+)A 2
      that could grow without LIF: we also obtained 13 pSVLD(-)-transfected clones (B 1
      13) which would differentiate in 60% BRL-CM, including ESL(-)B 3 and B 5 that
      could not be passaged without LIF. ESL(+)A 2 and ESL(-)B 5 cells had the
      relatively stronger LIF mRNA or antisense LIF RNA expression, and LIF
      overexpression in ESL(+)A 2 cells was shown by biological assay for ES cell
      differentiation inhibition. ESL(+)A 2 cells could be continuously passaged for at
      least 13 passages without addition of exogenous LIF, retained undifferentiated
      morphology as well as a high growth rate, and resembled ES-5 cells in terms of
      stem cell characteristics and pluripotent properties, as analyzed for alkaline
      phosphatase activity and with staining the paraffin sections of tumor formed by
      inoculating ESL(+) A 2 cells into mouse. On the contrary, ESL(-) cells should be
      cultured in higher concentration of LIF than ES-5 cells, otherwise, would
      undertake extensive differentiation. By hanging drop culture for 3 days in the
      presence of 10(-6) mol/L RA then observing the differentiation of the formed
      embryonic bodies (EBs), we found that ESL(+) A 2 and ES-5 cells underwent similar
      morphologically differentiation, with round and epitheliallike cells occurring
      around the EBs; while ESL(-) B 5 cells, despite initial differentiation to round
      cells, differentiate into fibroblast-like and spindle shaped cells. The above
      results indicate that LIF overexpression in ESL(+) A 2 cells is able to
      completely free ES cells from the dependence on LIF-conditioned medium, and
      endogenous LIF gene expression, although is very low, may be indispensable for
      inhibiting the differentiation in vitro of ES cells; LIF overexpression might not
      obviously change the differentiation way of ES-5 cells, however, blocking
      endogenous LIF expression gives rise to the increased sensitivity of ES-5 cells
      to differentiate, with an altered differentiation pattern. The establishment of
      ESL(+) and ESL (-) cell lines provides models for further study of the growth and
      differentiation of ES-5 cells.

PMID- 9772687
TI  - [LPS and PMA induced PKC-alpha and PKC-epsilon activation and translocation in
      murine peritoneal macrophages].
AB  - Suppressor macrophages induced by the continuous invasion of tumor cells and
      parasites, which can acquire an ability in vitro to kill or inhibit tumor cells
      and inhibit the activity of T, B lymphocytes and NK cells, have been indicated.
      We have developed a procedure previously to modulate the suppressor macrophages
      by bacterial lipopolysaccharide (LPS). The modulated macrophages remained and
      even enhanced the ability to inhibit tumor growth and to up-regulate or enhance
      the activities of T, B lymphocytes and NK cells in vitro. However, the mechanisms
      of macrophage modulation by LPS are unknown. This investigation was designed to
      analyze the regulation of PKC activity and to characterize the isoforms of PKC
      during macrophage modulation by using Western blot and endogenous substrate
      phosphorylation (PKC-DESP). In rest cells, PKC-beta was found to be the most
      abundant isoform in macrophages; and PKC-alpha, beta was found predominantly in
      the cytosol. Using PMA as a positive control, we found that the immuno-modulator
      agent--LPS triggered the physical translocation from the cytosol onto the
      membrane of PKC-alpha and PKC-epsilon, but PKC-beta (beta I or beta II) was
      difficult to detect. The analysis of PKC-DESP showed a pattern with a time course
      similar to that observed with Western blot. We observed that LPS and PMA increase
      the level of phosphorylation of 55 kDa and 74 kDa proteins with a corresponding
      decrease in the cytosolic proteins. It suggests that the translocation of PKC
      alpha and PKC-epsilon, may be important events involving in the PKC-pathway by
      LPS-mediated modulation in suppressor macrophages.

PMID- 9772688
TI  - [Anti-atrial fibrillation effects of cyclovirobuxine-D and its
      electrophysiological mechanism studied on guinea pig atria].
AB  - Cyclovirobuxine-D (CVB-D) was shown to produce significant and dose-dependent
      protective effects against atrial fibrillation induced by CaCl2-Ach in mice. On
      atrial fibrillation induced by aconitine, ouabain or adrenaline in isolated
      guinea pig atria, the effects of CVB-D were similar to those of amiodarone. CVB-D
      0.3-100 mumol.L-1 was shown to depress the automaticity of the isolated guinea
      pig right atria. In isolated left atria, CVB-D 0.3 mumol.L-1 was found to inhibit
      the abnormal automaticity elicited by adrenaline, to prolong the duration of
      action potential and effective refractory period and to reduce excitability. At
      high concentration (30 mumol.L-1), CVB-D was also found to decrease the maximal
      velocity of depolarization (Vmax) and to elongate the conduction time of
      initiation. Amiodarone 0.3-30 mumol.L-1 was shown to closely resemble CVB-D in
      electrophysiology without effect on Vmax.

PMID- 9772689
TI  - [Pharmacokinetic and electocardiographic study of oral verapamil sustained
      release tablet in 10 Chinese volunteers].
AB  - Both verapamil pharmacokinetics and electrocardio graphic changes in 10 Chinese
      volunteers were studied after po 240 mg of verapamil sustained release tablet. A
      one-compartment model with zero-order absorption gave a better fitting to
      concentration--time data with values of r2 > 0.96. The main pharmacokinetic
      parameters obtained were: Tmax, 5.9 +/- 1.6 h; Cmax, 118.9 +/- 37.2 micrograms.L
      1; T1, 5.4 +/- 1.5 h; k0, 30.5 +/- 17.5 micrograms.L-1.h-1; T1/2, 10.8 +/- 4.9 h;
      MRT, 15.4 +/- 3.2 h and AUC. 1.96 +/- 0.82 mg.h.L-1. There were significant
      prolongations of PR intervals after dose. Relationships between PR interval
      changes and plasma concentrations of verapamil were better fitted to sigmoidal
      model, with r2 > 0.98. The corresponding pharmacodynamic parameters were
      estimated. EC50, 64.6 +/- 16.9 micrograms.L-1, Emax, 54 +/- 11 ms and s, 1.68 +/-
      0.66.

PMID- 9772690
TI  - [Relaxing effects of l-stepholidine on rat resistance arteries].
AB  - Bolus injection(i.v.) of l-stepholidine(l-SPD, 3 mg.kg-1) caused hypotension in
      anaesthetized rats. The blood pressure reduction was sustained for 46.3 +/- 14.1
      min. In in vitro experiments, l-SPD induced a concentration dependent relaxation
      of rat mesenteric, cerebral, renal and coronary resistance arteries
      preconstricted with 125 mmol.L-1 KCl. l-SPD was least potent with cerebral
      resistance arteries with the -Log EC50 value being 4.25 +/- 0.22. The relaxation
      of l-SPD on mesenteric resistance arteries was the most potent with the -Log EC50
      value being 4.76 +/- 0.15. The larger influence of l-SPD (100 mumol.L-1) on the
      contraction induced by KCl in mesenteric than in cerebral arteries was in line
      with the above results. It is indicated that l-SPD has a direct relaxation on
      visceral resistance arteries with some degree of selectivity and the relaxation
      would decrease total peripheral resistance and thus constitute an important cause
      of its hypotensive action.

PMID- 9772691
TI  - [The structure activity relationship of saikosaponins and glycyrrhizin
      derivatives for Na+, K(+)-ATPase inhibiting action].
AB  - The study on structure-activity relationship of saikosaponins and glycyrrhizin
      derivatives for Na+, K(+)-ATPase inhibiting action has been made in vitro. The
      results showed that the order of potency of inhibitory effect of saikosaponins on
      Na+, K(+)-ATPase is as follows: b1 > d > b2 > b4 > a > b3 > e > c. The chemical
      structure C23-OH, C16-OH and the C11, C13 conjugated double diene of
      saikosaponins are important for its inhibitory activity. The inhibitory potency
      of glycyrrhizin (GL), glycyrrhetinic acid (GA) and carbenoxolone (CX) for Na+,
      K(+)-ATPase activity is as follows: GA > or = CX > GL. In addition, the
      inhibitory effect of saikosaponin d on Na+, K(+)-ATPase was found to be non
      competitive.

PMID- 9772692
TI  - [Studies of antitumor and chemopreventive agents against neoplasm: synthesis of
      coumarin 3-glyoxal derivatives and relationship between structure and
      antimutagenic activity].
AB  - It has been shown that alpha-glyoxal and its derivatives possess antivirus and
      antitumor activities. Eighteen new coumarin 3-glyoxal derivatives were
      synthesized in our laboratory. The fragmentation pattern of MS and the
      characteristic signals of 1HNMR of these compounds have also been studied. In
      pharmacological test in vitro most of these analogues showed antimutagenic
      activities, among them, compound 9 exhibited very strong antimutagenic activity
      and eight compounds showed strong effects. The struture-activity relationship and
      the possible active substructure responsible for the activity of these compounds
      were discussed. As expected, coumarin 3-glyoxals showed higher antimutagenic
      activities than their 3-acetyl coumarin counterparts. We also found that
      alkylation or esterification of 7-hydroxy were favorable to their activities.

PMID- 9772693
TI  - [Studies on the triterpenoid saponins of the root bark of Aralia taibaiensis].
AB  - Four triterpenoid saponins were isolated from the root bark of Aralia taibaiensis
      Z. Z. Wang et H. C. Zheng. On the basis of their chemical properties and spectral
      data, they were identified as oleanolic acid-3-O-[beta-D-xylopyranosyl(1-->2)]
      [beta-D-glucopyranosyl(1-->3)]-beta-D-glucuronopyranoside (1), tarasaponin V (2),
      3-O-?beta-D-xylopyranosyl(1-->2)[beta-D-glucopyranosyl (1-->3)]-6'-O-ethyl-beta-D
      glucuronopyranosyl?-oleanolic acid-28-O-beta-D-glucopyranoside (3) and 3-O-?beta
      D-xylopyranosyl(1-->2) [beta-D-glucopyranosyl(1-->3)] -6'-O-butyl-beta-D
      glucuronopyranosyl?-oleanolic acid-28-O-beta-D-glucopyranoside (4). Compound 1 is
      a new natural product named taibaienoside VI. 2 was isolated from the title plant
      for the first time. 3 and 4 are new compounds and named taibaienoside VII and
      taibaienoside VIII, respectively.

PMID- 9772694
TI  - [Studies on chemical constituents of roots of Euphorbia pekinensis].
AB  - Nine compounds were isolated from the roots of Euphorbia pekinensis Rupr., a
      traditional Chinese medicine. By combination of chemical methods and spectral
      analyses, the structures of the compounds were identified as lanosterol (I),
      octadecanyl-3-methoxy-4-hydroxybenzeneacrylate (II), beta-sitosterol (III), 7
      hydroxycoumarin (IV), 2, 2'-dimethoxy-3, 3'-dihydroxy-5, 5'-oxygen-6, 6'
      biphenylformic anhydride (V), d-pinoresinol (VI), quercetin (VII), 3, 4
      dimethoxybenzoic acid (VIII) and 3, 4-dihydroxybenzoic acid (IX). II and V are
      new compounds which have not been reported in the literature. The other compounds
      were isolated for the first time from this plant. VI is a lignan which was first
      isolated from the plants of genus of Euphorbia.

PMID- 9772695
TI  - [Fluorometric method for determination of nitric oxide and nitric oxide
      synthetase in rat brain].
AB  - A simple, sensitive fluorometric method for the determination of nitric oxide and
      nitric oxide synthetase in rat brain homogenates has been developed. The method
      is based on the absorption of a reaction product of N-acetylcysteine and nitric
      oxide overlapping the absorption of quinine sulfate. The lowest concentration
      that can be determined is 3 x 10(-8) mol.L-1.

PMID- 9772696
TI  - [Studies on a new type of all-solid-state atropine ion-selective electrode].
AB  - Using urea-formaldehyde resin as frame material and KCl powder as active
      component, a Ag/AgCl solid state electrode was prepared. Then, using the prepared
      Ag/AgCl solid state electrode as substrate and atropine tetraphenylborate ion
      pair complex as active component, a new type of all-solid-state atropine ion
      selective electrode was constructed. The properties of this electrode were
      studied in detail. The results indicate that the electrode showed good stability
      and can be used for potentiometric determination of atropine in pharmaceutical
      preparations.

PMID- 9772697
TI  - [Studies on metabolism of 6-methoxy butyl phthalide by rat liver microsomes].
AB  - The in vitro biotransformation of 6-methoxy butyl phthalide (MBP) by
      phenobarbital induced rat liver microsomes was investigated by GC/MS and GC/MS
      with TMS derivatization. Three major metabolites of MBP were identified as 3-OH
      MBP, 6-OH-butyl phthalide and gamma-OH-MBP. A less polar metabolite was
      tentatively identified as an epoxidation product.

PMID- 9772698
TI  - Authentication of the Chinese drug "ku-di-dan" (herba elephantopi) and its
      substitutes using random-primed polymerase chain reaction (PCR).
AB  - DNA fingerprinting and polymorphism among the Chinese drug "Ku-Di-Dan" and its
      substitutes were demonstrated with arbitrarily primed polymerase chain reaction
      (AP-PCR) and random amplified polymorphic DNA (RAPD). Distinctive, reproducible
      genomic fingerprints from DNA of the Chinese drug Ku-Di-Dan and 9 species of
      Compositae were generated with six long (18-24 mer) and one short (10 mer) random
      chosen primers with PCR. Ku-Di-Dan samples can be distinguished according to the
      banding patterns of their amplified DNA on agarose gels. Results showed that AP
      PCR and RAPD fingerprints of the commercial samples of Ku-Di-Dan retailed in
      Fujian, Taiwan, Hong Kong and Macau markets are identical with that of
      Elephantopus scaber L. The relatedness of Ku-Di-Dan among 9 plants may also be
      estimated by the Similarity Indexes values of the genomic DNA fingerprints.

PMID- 9772699
TI  - [The absolute configurations and biological activities of alpha- and beta
      anordrins].
AB  - The molecular structures and absolute configurations of alpha- and beta-anordrins
      are reported. Animal experiments showed that pure alpha-epimer possessed high
      anti-implantation and anti-early pregnancy effects, but the pure beta-epimer
      exhibited very low effects at the same dose. MNDO program was applied for the
      optimization of the configurations of epimers to establish the isolated molecular
      configurations and calculate the quantum chemical indexes. The results showed
      that the configurations and the differences of action field in three-dimensions
      of alpha- and beta-epimer are probably the factors that the alpha-epimer
      exhibited biological activity.

PMID- 9772700
TI  - [Isolation and identification of a new cinnamate ester from liaoxi propolis].
AB  - A new cinnamate ester drivitive (II) and three flavonoids (I, III, IV) were
      isolated from Liaoxi propolis. Their chemical structures were established as
      benzyl caffeate (II), 7-O-methylchrysin (I), genkwanin (III) and rhamnazin (IV)
      by spectral analysis. II is a new natural compound; I, III and IV were found from
      the propolis for the first time.

PMID- 9772701
TI  - [Seizure activity and lesions of neuronal cells by intrahippocampal injection of
      guanidinosuccinic acid in rats].
AB  - Intrahippocampal injection(ihci) of guanidinosuccinic acid (GSA) to rats, induced
      typical generarized clonic seizures and epileptiform discharges in
      electrohippocampogram (EHG) and electrocorticogram (ECoG), degenerative changes
      of neuronal cells in the injected side hippocampus. The pyramidal cells in CA1
      area were found to be more vulnerable to GSA than the granular cells.
      Phenobarbital and phenytoin are typical antiepiletics, but in no case did they
      successfully protect against GSA induced convulsions, epileptiform discharges in
      the EHG and ECoG and neurolysis. Ketamine, a selective noncompetitive NMDA
      receptor antagonist, was shown to protect against not only seizures, but also
      neuronal cell damage induced by GSA. All these results indicate that GSA very
      like the endogenous excitatory amino acid, glutamic acid, it also has such
      effects mentioned above. Therefore, the NMDA receptor may mediate both effects of
      GSA.

PMID- 9772702
TI  - Biotransformation and elimination of 1-nitropyrene in the isolated perfused lung:
      effects of pretreating rats with phenobarbitone, beta-naphthoflavone,
      benz(A)anthracene or their mixtures.
AB  - The isolated perfused rat lung (IPL) was perfused with 60 ml of recirculating
      Krebs-Ringer solution containing 150 micrograms of 1-nitropyrene (1-NP) for 1 h.
      The 1-NP was administered to the IPL by the intratracheal or intravascular route.
      At specific time points after 1-NP administration, perfusate samples were removed
      from the IPL and analysed for 1-NP and its metabolites by HPLC.
      Monohydroxynitropyrenes, dihydroxynitropyrenes and 1-NP were found to be present
      in the perfusate. The time course of 1-NP concentrations in the perfusate could
      be described by a one-compartment pharmacokinetic model. Pretreatment of rats
      with beta-naphthoflavone (BNF), benz(a) anthracene (BA) or a mixture of
      phenobarbitone (PB) and BNF (PB + BNF) significantly enhanced the metabolism of 1
      NP and decreased the mean residence time (MRT) of 1-NP in the perfusate.
      Pretreatment of rats with these mixed-function oxidase inducers also increased
      significantly the absorption of 1-NP by the lung when it was administered
      intratracheally. In contrast, pretreatment of rats with PB did not appear to have
      any effect on the pharmacokinetics of 1-NP in the IPL.

PMID- 9772703
TI  - [Effect of silymarin on mouse liver damage, production and activity of tumor
      necrosis factor].
AB  - Tumor necrosis factor (TNF) has been well-characterized as a prominent mediator
      in the development of liver injury. Effects of silymarin (SB) on mouse liver
      damage, TNF production and activity were studied. Pretreatment with SB (25-50
      mg.kg-1, i.p., bid x 3 d) before the lipopolysaccharides (LPS) injection markedly
      alleviated liver injury and diminished LPS-induced TNF production in
      Propionibacterium acnes (PA)-primed mice. SB (12.5-50 micrograms.ml-1)
      significantly inhibited LPS-induced TNF release from mouse peritoneal macrophage
      in a concentration-dependent manner. SB(12.5-100 micrograms.ml-1) was also shown
      to markedly reduce TNF cytotoxicity on human hepatic cell line GSG-7701 and mouse
      fibroblastic cell line L929 cells concentration-dependently. These results
      suggest that inhibition of TNF production and its actions may be involved in the
      mechanism of protective action of SB on liver damage.

PMID- 9772704
TI  - [Inhibition of guan-fu base A on delayed rectifier current (Ik) in guinea pig
      ventricular myocytes].
AB  - Guan-fu base A (GFA) is a terpenoid alkaloid isolated from the tuber of Aconitum
      coreanum, which has been shown to prolong cardiac repolarization in vivo and in
      vitro. In the present study, the effects of GFA on the delayed rectifier current
      (Ik) were investigated using the whole cell patch-clamp technique in isolated
      guinea pig ventricular myocytes. In the presence of CdCl2 100 mumol.L-1, Ik was
      observed upon depolarizing pulses to +50 mV from a holding potential -40 mV for
      variable duration (550, 1100, 1650, 2200, 2750, 3300, 3850 ms). The magnitude of
      Ik after a 2200 ms pulse was 293 +/- 90 pA prior to drug and 227 +/- 59 pA in the
      presence of GFA 100 mumol.L-1. In a 3850 ms pulse, the magnitude of Ik decreased
      from 290 +/- 90 to 231 +/- 66 pA after exposure to GFA. The inhibitory effects of
      GFA on Ik was not dependent on the duration of depolarization. The inward
      rectifier current (Ik1) was not affected by GFA 100 mumol.L-1. It is concluded
      that GFA has inhibitory effects on Ik, which may contribute to its prolongation
      of cardiac repolarization.

PMID- 9772706
TI  - [Structure determination of korepimedoside A and korepimedoside B from Epimedium
      koreanum Nakai].
AB  - Two new flavonol glycosides were isolated from the aerial parts of Epimedium
      koreanum Nakai. On the basis of spectroscopic and chemical evidence, they were
      elucidated as anhydroicaritin 3-O-beta-D-(6-acetyl) glucopyranosyl (1-->3)-alpha
      L-(4-acetyl) rhamnopyranoside and anhydroicaritin 3-O-beta-D-(2, 6-diacetyl)
      glucopyranosyl (1-->3)-alpha-L-(4-acetyl) rhamnopyranoside-7-O-beta-D
      glucopyranoside, which were named korepimedoside A and korepimedoside B
      respectively.

PMID- 9772705
TI  - [Preparation of hepatic targeting antivirus agent NGA-ACV and its targeting
      property].
AB  - Neoglycoalbumin (NGA), a special ligend of asialoglycoprotein receptor on the
      hepatocyte, was linked via a butanediacyl bridge to acyclovir to form a conjugate
      NGA-ACV. By using DTA (Differential thermoanalysis) and HPLC analysis, ACV was
      shown to be connected with NGA by covalent bonds and stable in blood. The radio
      biodistribution of 131I-NGA-ACV with high drug density in vivo was carried out in
      mice. The maximum absorption of 131I-NGA-ACV in liver was 81.7 +/- 10.4% at 5
      min. The radioimage of 131I-NGA-ACV with high or low drug density in rabbit
      showed no significant difference in liver targeting property. The competitive
      connection tests indicated that 131I-NGA-ACV was concentrated in liver through
      receptor mediated mechanism. A tentative test of antihepatitis B of NGA-ACV and
      ACV in vitro showed that the effective dose of the former was significantly lower
      than that of the latter.

PMID- 9772707
TI  - [Two new steroidal saponins from Allium sativum and their inhibitory effects on
      blood coagulability].
AB  - Six compunds were isolated from the fresh bulbs of Allium sativum L (garlic).
      Their structures were elucidated as proto-iso-eruboside-B (I), eruboside-B (II),
      iso-eruboside-B (III), sativioside C (IV), adenosine (V) and tryptophan (VI). I
      and III are new steroidal saponins. This paper deals with the structural
      determination of I and III and their effects on platelet aggregation, blood
      coagulation and fibrinolysis in vitro.

PMID- 9772708
TI  - [Studies on the chemical constituents of Dregea sinensis Hemsl].
AB  - Two new compounds named dresigenin B and dresioside I were isolated from the root
      of Dregea sinensis Hemsl. Their structures were demonstrated as 20-O-(2
      methylbutyryl) tomentogenin and dihydrosarcostin 3-O-beta-D-thevetopyranosyl (1
      4)-beta-D-oleandropyranosyl (1-4)-beta-D-cymaropyranoside by spectral evidence.

PMID- 9772709
TI  - [Studies on the metabolites of tetramethylpyrazine in rabbits].
AB  - The metabolites of tetramethylpyrazine (TMPz) in rabbit have been separated by
      HPLC and solvent extraction. Their structures were identified by means of UV, IR,
      MS and NMR spectroscopy. The possible metabolic ways of TMPz are oxidzation of
      one of the four methyl groups to hydroxymethyl and carboxyl group forming 2
      hydroxymethyl-3, 5, 6-trimethylpyrazine (TMPz D1) and 3, 5, 6-trimethylpyrazine-2
      carboxylic acid (TMPz D2). These were further confirmed by the identity of HPLC
      data and all the above spectral parameters of the metabolites in vivo and the
      compounds objectively synthesized from TMPz.

PMID- 9772710
TI  - [HPLC determination of five constituents in plants of genus Ligusticum].
AB  - A RP-HPLC method was established to separate and determine five constituents in
      plants of genus Ligusticum by using an ODS column (Hypersil-C18, 5 microns) and
      acetonitrile (containing 1.25% CHCl3)--water (saturated with CHCl3) as mobile
      phase for gradient elution. The five constituents were ferulic acid, scopoletin,
      3-butyl-phthalide, ligustilide, and diligustide. They were detected at 284 nm.
      Peak purity was monitored by photodiode array detector. Benzthiazide was used as
      the internal standard. The method is simple, fast, sensitive and reproducible.

PMID- 9772711
TI  - [Study on the mitoxantrone ethylcellulose microspheres for liver artery
      embolization].
AB  - In this paper, orthogonal test was used to optimize the preparation conditions
      and technique of mitoxantrone ethylcellulose microspheres (DHAQ-EC-MS) for liver
      embolization. The dynamic osmosis method was used to study the drug release
      characteristics of DHAQ-EC-MS. DHAQ-EC-MS suspension for clinical liver artery
      embolization was prepared. The result showed that the DHAQ-EC-MS is regular in
      its morphology with a mean diameter of 110.24 +/- 38.19 microns. The drug loading
      was 12.5% and embedding ratio was 55.6%. The release characteristics was in
      accord with single exponential model. The drug release equation is lg(Yinfinity -
      Y) = -0.116t - 1.198 x 10(-3) (gamma = 0.9992, t50 = 2.6 h). The DHAQ-EC-MS was
      shown to be physically and chemically stable and its suspension is suitable for
      clinical use. Experiments in dogs indicate that drug concentration of DHAQ-EC-MS
      in hepatic vein blood was higher than DHAQ solution, and the MRT0-72 was 2.45
      times higher than DHAQ solution.

PMID- 9772712
TI  - [Preparation and in vitro activity of monoclonal antibody-pharmorubicin
      immunoconjugates].
AB  - Bifunctional agent adipic dihydrate was used to form hydrazon bond between
      polyglutamic acid (PGA) and pharmorubicin (PAR). Under controlled condition, a
      relatively high rate of conjugation was obtained with no self-condensation. The
      value of PGA/PAR was in positive portion with the molecular weight (MW) of PGA:
      per 8-11 glutamic acid monomer linking one pharmorubicin. When PGA of MW 14,300
      was used as carrier, the ratio of PGA/PAR was 1:11. After conjugating with anti
      hepatoma monoclonal antiboty (McAb), an immunoconjugate of McAb:PGA:PAR being
      1:2:22 was obtained. The immunoconjugate retained the binding activity to
      targeted cell compared with the purified and the oxidized antibody.
      Pharmacological studies in vitro showed lower cytotoxicity of the immunoconjugate
      than the free drug, but selective cytotoxicity directed by antibody was observed.
      Consequently, the immunoconjugate McAb-PGA-PAR with high ratio of drug/McAb as
      well as moderate targeting cytotoxity in vitro was successfully prepared. That
      makes it possible for the preparation of cell-targeted drug which is expected to
      be benificial to tumor treatment.

PMID- 9772713
TI  - Separation of five antipyretic analgesics by micellar electrokinetic capillary
      chromatography.
AB  - The derivatives of antipyrine and phenylbutazone are important antipyretic
      analgesics commonly used in clinical medicine. Although high performance liquid
      chromatography has been the conventional method used for the analysis of these
      drugs, in recent years capillary electrophoresis was validated to be a useful
      method in the analysis of antipyretic analgesics. However, there has been no
      report on the separation of antipyrine (AP), 4-aminoantipyrine (4-AAP),
      aminopyrine (APY), dipyrone (DIP) and phenylbutazone (PHE) in the literature. In
      this paper, a micellar electrokinetic capillary chromatographic (MECC) separation
      method was described for the five antipyretic analgesics.

PMID- 9772714
TI  - [Value of angiotensin II-antagonists].

PMID- 9772715
TI  - [Budesonide: effective, with low side effects. On the road to new treatment
      methods in Crohn disease].

PMID- 9772716
TI  - [Social reintegration thanks to improved cognition].

PMID- 9772717
TI  - [Cabergolin: new horizons in the therapy of Parkinson diseases].

PMID- 9772718
TI  - [The breeding of Culicoides nubeculosus (Diptera: Ceratopogonidae)].
AB  - The authors give their own procedure for rearing during 25 years the Diptera
      Ceratopogonidae Culicoides nubeculosus. The only purpose of this technical note
      is to transmit a method.

PMID- 9772720
TI  - The expulsion of Echinostoma trivolvis caused by goblet cell hyperplasia in
      severe combined immunodeficient (SCID) mice.
AB  - Mice with severe combined immunodeficiency (SCID), lacking functional T and B
      lymphocytes, were each infected with 40 Echinostoma trivolvis metacercarial cysts
      on day 0. The mice of the test group were given intramuscular injections of
      dexamethasone (DEX) daily for 2 weeks and necropsied on days 5, 8, 12, 15, 20 and
      30 post-infection (p. i.). The control mice, not treated with DEX, were each
      infected with 40 echinostome cysts on day 0 and necropsied on the same days as
      the DEX-treated mice. In the control mice, worm rejection began about day 8 p. i.
      and the worms were completely rejected by day 15 p. i., corresponding to the peak
      in goblet cell hyperplasia, about day 12 p. i. In the DEX-treated mice, goblet
      cell hyperplasia was significantly suppressed and the worms were retained until
      day 15 p. i., and then rejected after the last treatment with DEX. The number of
      mucosal mast cells, that increased with worm infection and peaked about day 15 p.
      i., was apparently suppressed by treatment with DEX. The eosinophil number in the
      controls increased on day 15 p.i. approximately and then decreased. The
      eosinophil number in the DEX-treated mice increased as in the controls, but was
      significantly suppressed compared to that of the controls during the period of
      the experiment. Enzyme-linked immunosorbent assay (ELISA) showed no marked rise
      in titres of the sera IgM, IgA and IgG throughout the experiment in both groups.
      These results indicate that DEX-treatment delayed the rejection of E. trivolvis
      from the small intestine of SCID mice in association with the suppression of
      goblet cell hyperplasia. It is concluded that the host immune system is not
      involved in the rejection of E. trivolvis and the effector cells for worm
      rejection are goblet cells that markedly increase in numbers by infection with E.
      trivolvis.

PMID- 9772719
TI  - Toxoplasma gondii infection in rats by the RH strain: inoculum and age effects.
AB  - Toxoplasma gondii strains are classified according to their virulence in mice.
      Rats are considered to be resistant to the infection, depending on the age.
      Newborn rats are fully susceptible but weaned rats are resistant. However the
      effect of inoculum has not been examined. Using RH strain inocula of 10(2),
      10(4), 5 x 10(7) and 10(8) tachyzoites intraperitoneally inoculated into Wistar
      and Fischer rats of 7, 11, 21, 24 and 46 days old, the authors show that inoculum
      and not the age of the host had a statistically significant effect (p < 0.01) on
      the survival curve.

PMID- 9772721
TI  - Assessment of the activity of atovaquone-loaded nanocapsules in the treatment of
      acute and chronic murine toxoplasmosis.
AB  - The aim of this work was to develop a new pharmaceutical form of atovaquone and
      to study its activity against Toxoplasma gondii in vitro and in vivo.
      Nanocapsules were chosen as the oral dosage form of administration. An analytical
      method was developed to determine the drug content in nanocapsules. The stability
      of these nanocapsules were assessed by following drug content, size, pH and
      osmolarity for a period of six months. The in vitro activity of atovaquone-loaded
      nanocapsules against tachyzoites of T. gondii (RH stain) was comparable to its
      suspension form. In vivo studies were carried out in murine models of acute and
      chronic toxoplasmosis. Mice acutely infected with the virulent RH strain were
      orally treated with a dose regimen of 15 mg/kg/day for 10 days, starting from day
      1 post-infection. 75% of the mice receiving atovaquone-loaded nanocapsules
      survived 30 days post-infection, compared to none of untreated controls and none
      of mice treated with the suspension with the same dose regimen. In mice
      chronically infected by the COUL or the ME49 strain (Type II strains), then
      treated for six weeks, treatment with atovaquone (15 mg/kg/d, nanoparticles or
      suspension) resulted in a decrease of brain parasitic burden, which was
      significantly more pronounced in ME49-infected mice and in those treated with
      drug-loaded nanocapsules. These results show that the sensibility of T. gondii to
      atovaquone is different according to the strains and that the activity of
      atovaquone in the treatment of toxoplasmosis is enhanced when administered in
      nanoparticular form.

PMID- 9772723
TI  - Studies on lipidomimetic derivatives of alpha-difluoromethylornithine (DFMO) to
      enhance the bioavailability in a Trypanosoma B. brucei murine trypanosomiasis
      model.
AB  - DFMO, a trypanostatic drug, presents a satisfactory intestinal absorption but its
      elimination from the blood is rapid so that high doses are necessary to obtain to
      therapeutic effect. In this study, we propose a strategy to enhance the
      bioavailability of DFMO by using lipidomimetic derivatives. Three lipidomimetic
      DFMO derivatives called O-DFMO, S-DFMO and Chol-DFMO were designed to reach
      easily the plasma and to be cleaved preferentially by plasma esterases
      progressively liberating free DFMO. Chol-DFMO only could be cleaved partially
      whereas the other compounds appeared to be stable in reconstituted intestinal
      medium and mouse plasma. Nevertheless, the use of DFMO derivatives in T. b.
      brucei experimental chemotherapy appeared as an interesting approach. Thus, O
      DFMO was trypanocidal in vitro whereas DFMO, the active principle, was only
      trypanostatic. Nevertheless, this compound did not release DFMO in mouse blood as
      expected and acted therefore not as a prodrug. Oral treatment using low doses of
      compound O-DFMO was able to cure 40% mice while the active principle
      (eflornithine) administered at 50 fold higher molarity failed to cure any mice.
      This indicates that compound O-DFMO acts by a specific mechanism which remains to
      be investigated. S-DFMO was less active and Chol-DFMO had no in vitro activity
      but released small amounts of DFMO in mice, however, too slight to obtain a
      therapeutic effect.

PMID- 9772722
TI  - Echinococcus multilocularis infection in mice: in vivo treatment with a low dose
      of IFN-gamma decreases metacestode growth and liver fibrogenesis.
AB  - As no antiparasitic drug is definitively efficient in patients with alveolar
      echinococcosis, the effects of exogenous IFN-gamma on murine Echinococcus
      multilocularis infection were assessed with regards to the parasite burden,
      parasite-specific immune responses, and the urinary level of the collagen cross
      link pyridinolines. They were analyzed after 3-week treatments with 1 or 5
      micrograms of IFN-gamma per day twice a week. The treatment with 1 microgram
      transiently reduced the liver metacestode load, and the metastase weight as far
      as 6 weeks after the end of treatment. It slightly increased Th 1-type T cell
      responses and reduced the excretion of pyridinolines. These results should
      encourage further study to assess whether the decrease in liver fibrosis leads to
      an improvement of the efficacy of albendazole therapy. In contrast, the treatment
      with 5 micrograms increased the liver metacestode load and was less efficient
      than that with 1 microgram in decreasing pyridinoline excretion. These results
      incitate to follow up carefully patients with alveolar echinococcosis who are
      treated with IFN-gamma.

PMID- 9772724
TI  - Some ultrastructural data on Microsporidium ceylonensis, a cause of corneal
      microsporidiosis.
AB  - Sections of corneal tissue infected with Microsporidium ceylonensis were
      restained or processed for electron microscopy. Confirmation was obtained that
      the parasite develops in macrophages and that spores are uninucleate. New
      information is provided that sporoblasts and spores develop synchronously within
      a membrane in the host cell, spores have an anisofilar polar tube of 6-10 wide
      coils and 2-3 narrow coils and details are given of the spore wall and internal
      organisation. The parasite was compared on the one hand with Encephalitozoon,
      which exhibits asynchronous intravacuolar development of merogonic and sporogonic
      stages and has spores with isofilar polar tubes and on the other hand with
      species reported from mammals, of which the sporogonic stages develop
      synchronously within sporophorous vesicles and the spores have anisofilar polar
      tubes. Even so, a generic emplacement could not be established. Attention is
      drawn to the similarities between M. ceylonensis and Nosema sp. described from
      the cornea of a woman in Botswana.

PMID- 9772725
TI  - Halicephalobus gingivalis (Stefanski, 1954) from a fatal infection in a horse in
      Ontario, Canada with comments on the validity of H. deletrix and a review of the
      genus.
AB  - Although the original description given by Stefanski (1954) was satisfactory,
      Anderson & Bemrick (1965), in describing H. deletrix (= Micronema deletrix),
      claimed Stefanski's description was "inadequate" and the species a "species
      inquirenda". Thus, infections in horses and humans have been assigned to H.
      deletrix. We believe the species reported in horses and humans is H. gingivalis
      and that H. deletrix is its synonym. H. gingivalis is separated herein from forms
      found free-living. The genital tract in the advanced fourth stage of H.
      gingivalis is didelphic and amphidelphic and terminal ends of the horns are
      reflected, the anterior one ventrally, the posterior one dorsally. In the adult
      parthenogen the latter forms a short ovary, whereas most of the anterior horn
      forms a combined uterus-oviduct as a receptacle for a single large egg which is
      laid in the 2-cell or multi-cell stage. Eggs in the 2-cell stage embryonated to
      larvae in 17 hours at 28 degrees C but did not hatch until an additional 24
      hours. First-stage larvae were unusually large and variable in length (136-199
      microns x = 168). Inactive third-stage larvae were 180-240 microns (x = 203) in
      length. The possible route of infection in horses and humans is briefly
      discussed.

PMID- 9772727
TI  - Plasmodium falciparum-isolates from Cameroonian pregnant women do not rosette.
AB  - The placenta of pregnant women is frequently parasitized by erythrocytes infected
      by mature stages of Plasmodium falciparum (IE), a phenomenon associated with low
      birth weight of the offspring. The cytoadherence phenotype of the parasites from
      pregnant women suggests that placental sequestration may result from
      cytoadherence to the syncytiotrophoblast. However, as anatomopathological studies
      report that cytoadherence in the placenta is a rare event, we investigated
      whether placental parasites may sequester by forming rosettes with uninfected
      erythrocytes, another possible sequestration mechanism. Parasites from placental
      blood as well as parasites from the peripheral blood of pregnant and non pregnant
      subjects were assessed for their ability to rosette. In non pregnant subjects,
      the rosetting capacity of parasites was as reported in literature while, except
      in one case, parasites from pregnant women did not rosette. We conclude that the
      lack of rosetting is a new feature of IEs from pregnant women and that rosetting
      cannot be involved in the placental sequestration of IEs.

PMID- 9772726
TI  - [Comparative evaluation of the plasmodial infection of Anopheles using ELISA and
      dissection. Consequences for the estimation of the transmission of malaria in
      1995 in Ndiop, Senegal].
AB  - An entomological study was carried out in Ndiop village, Senegal, an area of
      sudan-type savana, from January to December 1995, to compare the malaria
      inoculation rate measured by the dissection of salivary glands of anophelines and
      the enzyme-linked immunosorbent assay (ELISA). Mosquitoes were sampled by night
      bite collections. Species from the Anopheles gambiae complex were identified
      using the polymerase chain reaction. 1292 females Culicidae were collected. 597
      anophelines mosquitoes known to be malaria vectors were captured during 148 man
      nights of capture. Of the 572 anophelines investigated, 14 were positive using
      dissection while 21 were found to be positive with ELISA. The sporozoite rates
      were 2.5%, 2.2% and 3.8% for An. arabiensis, An. gambiae and An. funestus,
      respectively. The circumsporozoite rates were 3.5%, 2.2% and 7.7% for these three
      species, respectively. ELISA detected 1.5 times more positive mosquitoes than
      dissection. These results are discussed with reference to the duration of the
      sporogonic cycle, the delay before CSP antigens are apparent, and the daily
      survival rate of Anopheles mosquitoes.

PMID- 9772728
TI  - [Alveolar echinococcosis in the French province of Ardennes: isolated case or new
      focus?].
AB  - The first three autochthonous cases of alveolar echinococcosis were diagnosed in
      the Ardennes area (France). This is the most occidental localization of this
      disease in Northern Europe. The authors discuss these cases with an
      epidemiological regard. They are looking for relationships with natural parasitic
      cycle in the neighbouring country Belgium and their consequences on local public
      health in the future.

PMID- 9772729
TI  - New observations on Mexiconema cichlasomae (Nematoda: Dracunculoidea) from fishes
      in Mexico.
AB  - The dracunculoid nematode Mexiconema cichlasomae Moravec, Vidal et Salgado
      Maldonado, 1992, originally described from the abdominal cavity and viscera of
      Cichlasoma spp. from Mexico, was recorded from the abdominal cavity of the
      poeciliid Xiphophorus helleri Heckel in Lake Catemaco and its small tributary
      Arroyo Agrio, Veracruz and from the intestine of the nurse shark Ginglystoma
      cirratum (Bonnaterre) off the southern coast of the Gulf of Mexico in Campeche;
      both these findings represent new host records. The nematode specimens from these
      hosts are briefly described and illustrated. Whereas X. helleri evidently served
      as the true definitive host of this parasite, G. cirratum probably acquired
      Mexiconema infection accidentally while feeding on fish definitive hosts in the
      brackish or salt-water environment. The ability of M. cichlasomae to utilize
      fishes of different orders (Perciformes and Cyprinodontiformes) as definitive
      hosts is rather exceptional among dracunculoid nematodes.

PMID- 9772730
TI  - Gorging response of wild Anopheles arabiensis using membrane feeder with
      Baudruche or Parafilm.

PMID- 9772731
TI  - Innovative community services for rape victims: an application of multiple case
      study methodology.
AB  - A qualitative multiple case study design was used to examine communities across
      the United States that have developed coordinated community-based programs to
      assist rape victims. Previous studies have suggested that coordinated community
      programs help victims obtain needed resources and services. This study provided a
      follow-up examination of how and why these programs are helpful to rape victims.
      In-depth interviews were conducted with rape victim advocates, rape crisis center
      directors, police officers, prosecutors, doctors, nurses, and rape survivors from
      22 communities with coordinated programs. A comparison sample of 22 communities
      with fewer coordinated programs was also obtained. Results indicated that the
      high coordination communities had three types of programs to address sexual
      assault: coordinated service programs, interagency training programs, and
      community-level reform groups. Although not all of these programs directly
      address service delivery for rape victims, they help create a community culture
      that is more responsive to victims' needs. The research team and participants
      developed an explanatory model of why these program are effective in addressing
      rape victims' needs. This model hypothesizes that coordinated programs reflect an
      understanding of the multiple contexts of service delivery and embody that
      knowledge in services that are consistent with victims' needs. Narrative data
      from the interviews with service providers and rape survivors are used to develop
      and support this model.

PMID- 9772732
TI  - A qualitative evaluation of school-based family resource and youth service
      centers.
AB  - As part of the Kentucky Education Reform Act, school-based Family Resource/Youth
      Service Centers were commissioned to address those poverty-related issues that
      attenuate children and youths' coming to school prepared to learn. The centers
      had flexible mandates and were to adapt their service profiles to local urban,
      suburban and rural communities. A variety of grounded, inductive qualitative
      strategies were employed in an implementation evaluation that yielded profiles or
      domains of program elements, and descriptions of implementation strategies and
      impact on participants. These program descriptors were considered accurate by
      program personnel, formed the basis for training new program coordinators, and
      have served as reliable predictors of educational outcomes for program
      participants, thus affirming the utility of the qualitative evaluation
      approaches.

PMID- 9772733
TI  - Using qualitative methods to develop contextually relevant measures and
      preventive interventions: an illustration.
AB  - Qualitative methods were used to develop a contextually relevant quantitative
      measure of parenting stress and inform the design of family-focused interventions
      aimed at preventing adolescent mental and behavioral health problems. The study
      focused on the experiences of low-income one- and two-parent families
      representing three ethnic groups (Mexican, African, and European Americans)
      living in low-income neighborhoods in a large Southwestern city. This report
      describes the place of this study in a broader program of prevention research,
      the qualitative methods and data analysis procedures employed, and how the
      results were used to develop a new measure of parenting stress and inform future
      program design. The report also includes reflective comments on the methods used
      and lessons gained.

PMID- 9772734
TI  - Preparing the way: a qualitative study of high-achieving African American males
      and the role of the family.
AB  - Employed qualitative methods to examine the role of the family in the academic
      success of very high-achieving African American males. Findings revealed a
      complex tapestry of family processes and contexts involved in each youth's
      journey to outstanding academic achievement. Specifically, the combined
      importance of parental-determined academic engagement, strict discipline,
      nurturance, and community connectedness appeared to counteract potentially
      negative contextual influences of neighborhood, peers, schools, and society. The
      qualitative findings tell a multifaceted, rich, and compelling story of the
      pathways to academic success for Black males, and highlight the need for culture
      specific and ecologically based conceptualization, research, and intervention
      approaches.

PMID- 9772735
TI  - Determination of diethanolamine and N-nitrosodiethanolamine in fatty acid
      diethanolamides.
AB  - Diethanolamine (DEA) is a precursor of N-nitrosodiethanolamine (NDELA), an animal
      carcinogen. A gas chromatographic (GC) method was developed for determining DEA
      in fatty acid diethanolamides that are commonly used in cosmetic products.
      Methanolic solutions of the amides were analyzed by GC with flame ionization
      detection on either a wide-bore methyl silicone (Rtx-1) or 95% dimethyl--5%
      diphenyl polysiloxane (SPB-5) capillary column. Recovery of DEA from fatty acid
      dialkanolamides at fortification levels of 0.50, 1.00, and 5.00% ranged from 94
      to 100%. In a survey of commercial fatty acid diethanolamides, DEA was found at
      levels ranging from 1.1 to 14.0%, and most were in good agreement with
      manufacturer's DEA specifications. Fatty acid diethanolamides also were anlayzed
      for NDELA by liquid chromatography interfaced to a thermal energy analyzer.
      Recovery of NDELA from fatty acid diethanolamides at fortification levels of 50,
      100, and 200 ppb averaged 95%. No NDELA was found in any of the fatty acid
      diethanolamide samples analyzed.

PMID- 9772736
TI  - Detection of thiazide-based diuretics in equine urine by liquid
      chromatography/mass spectrometry.
AB  - Thiazide-based diuretics are included in the list of banned drugs in the horse
      racing industry. One effect of their misuse is increased urine flow, contributing
      to dilution of other doping agents. Their determination is essential in ensuring
      compliance to horse-racing regulation. This study evaluates the feasibility of
      using liquid chromatography/mass spectrometry (LC/MS) with electrospray and
      atmospheric pressure chemical ionization interfaces to analyze thiazidic
      diuretics in equine urine samples. Existing LC and gas chromatography/MS methods
      are limited in their applicability to thiazide analysis. Sample preparation,
      analyte extraction, chromatographic separation, ion-source collision induced
      dissociation, solvent composition, ionization mode, and ion polarity are
      discussed. The practicality of LC/MS for this analysis is demonstrated with
      actual equine administration samples collected at specified time intervals.
      Detection limits were 270 ng/mL for chlorothiazide, 131 ng/mL for
      hydrochlorothiazide, and 384 ng/mL for trichlormethiazide.

PMID- 9772737
TI  - Determination of pseudoephedrine hydrochloride and carbinoxamine maleate in
      combination drug formulation by liquid chromatography.
AB  - An isocratic, reversed-phase liquid chromatographic (LC) method was developed for
      simultaneous determination of pseudoephedrine hydrochloride (I) and carbinoxamine
      maleate (II) in a pharmaceutical dosage form. Analysis was conducted on a CN
      column (10 microns), with a mobile phase consisting of acetonitrile-methanol
      phosphate buffer (pH 5.3)-water (140 + 170 + 40 + 100) and at a detection
      wavelength of 262 nm. The method was validated for linearity, precision, system
      reproducibility, and accuracy. Recoveries at 80-120% of labeled claim ranged from
      97.4 to 100.7% and from 98.5 to 100.2% for I and II, respectively. Results were
      linear (correlation coefficient, r > 0.9995 for I in the range 250-750
      micrograms/mL and r > 0.9999 for II in the range 20-60 micrograms/mL.

PMID- 9772738
TI  - A screening method for beta-lactams in tissues hydrolyzed with penicillinase I
      and lactamase II.
AB  - Antibiotic residues above tolerance levels are not allowed in foods derived from
      farm animals. Microbial inhibition assays are used to screen antibiotics in U.S.
      regulatory laboratories. We developed a screening approach to classify beta
      lactams through selective hydrolysis of the beta-lactam ring with Penase or
      lactamase II, thereby inactivating the beta-lactam activity. Optimum conditions
      for hydrolysis of beta-lactams with Penase and lactamase II were determined. beta
      Lactams were detected by a microbial inhibition assay and with enzyme-linked
      immunosorbent assays before and after hydrolysis. beta-Lactams (10-100 ppb) were
      spiked in kidney extracts and hydrolyzed. Results indicate a pattern that
      tentatively classified the beta-lactams into 3 subgroups. Desfuroyl-ceftiofur
      cysteine, a major metabolite of ceftiofur, was clearly detected. Penicillin G,
      ampicillin, amoxicillin, and cloxacillin were distinguishable from cephapirin,
      ceftiofur metabolite, and high levels of hetacillin. Liver and kidney tissue
      samples were analyzed with the combined enzyme hydrolysis and screening assays,
      which tentatively identified the residues. This approach can speed up screening
      analysis of beta-lactam residues prior to identification and quantitation by
      chromatographic analysis, thus enhancing positive identification of residues to
      provide a safer food supply.

PMID- 9772739
TI  - Determination of cephapirin and ceftiofur residues in bovine milk by liquid
      chromatography with ultraviolet detection.
AB  - A method capable of quantitating cephapirin at a level fo 20 ng/mL and ceftiofur
      at a level of 50 ng/mL was developed for raw bovine milk. Raw bovine milk is
      deproteinated with acetonitrile. The supernatant is collected and then
      acetonitrile is removed under reduced pressure while warming in a water bath at
      40 degrees-50 degrees C. The extract is mixed with water and loaded onto a
      conditioned C18 solid-phase extraction column. Analytes are eluted with
      acetonitrile, which is removed completely under a stream of nitrogen gas.
      Analytes are separated from coextractives by gradient elution with an ion-pair
      mobile phase on a reversed-phase column and are detected by ultraviolet
      absorbance at 290 nm. Mean recoveries from fortified milk samples ranged from 79
      to 87% for cephapirin and from 76 to 86% for ceftiofur, with intralaboratory
      coefficients of variation ranging of 6-10% and 7-14%, respectively.

PMID- 9772741
TI  - Liquid chromatographic determination of histamine in fish, sauerkraut, and wine:
      interlaboratory study.
AB  - An interlaboratory study of the liquid chromatographic (LC) determination of
      histamine in fish, sauerkraut, and wine was conducted. Diminuted and homogenized
      samples were suspended in water followed by clarification of extracts with
      perchloric acid, filtration, and dilution with water. After LC separation on a
      reversed-phase C18 column with phosphate buffer (pH 3.0)--acetonitrile (875 +
      125, v/v) as mobile phase, histamine was measured fluorometrically (excitation,
      340 nm; emission, 455 nm) in samples and standards after postcolumn
      derivatization with o-phthaldialdehyde (OPA). Fourteen samples (including 6 blind
      duplicates and 1 split level) containing histamine at about 10-400 mg/kg or mg/L
      were analyzed singly according to the proposed procedure by 11 laboratories.
      Results from one participant were excluded from statistical analysis. For all
      samples analyzed, repeatability relative standard deviations varied from 2.1 to
      5.6%, and reproducibility relative standard deviations ranged from 2.2 to 7.1%.
      Averaged recoveries of histamine for this concentration range varied from 94 to
      100%.

PMID- 9772740
TI  - Delvotest SP for detection of cloxacillin and sulfamethoxazole in milk: IDF
      interlaboratory study. International Federation Dairy.
AB  - Under the auspices of the International Dairy Federation's Group E503, a
      collaborative study of the Delvotest SP multiplate microbial inhibitor test was
      performed to gain information about the detection limits of 2 antimicrobial
      agents (a beta-lactam and a sulfa compound), the variation of test results
      between users and 2 batches of the test, and the reasons for deviating results.
      Lyophilized milk samples spiked with various concentrations of cloxacillin or
      sulfamethoxazole were analyzed. Each substance/concentration combination was
      tested with each of 2 test batches 14 or 15 times per participating laboratory.
      Test results were to be read by more than one person and reported on separate
      forms. Results were obtained from 29 laboratories, which included 5 with no
      experience and 11 with limited experience with this test. Detection limits for
      cloxacillin (22.5 or 30 micrograms/kg, depending on batch) and sulfamethoxazole
      (45 micrograms/kg) were established from dose-response curves. A small difference
      in cloxacillin detection levels between the 2 test batches was observed. Analyses
      of samples gave almost unanimous results (> or = 95%). Of deviating results,
      defined as anomalous results (1.4% of readings), half could be attributed to
      human errors and half to procedural errors.

PMID- 9772742
TI  - High-performance liquid chromatographic method for the determination of
      moniliformin in corn.
AB  - A high-performance liquid chromatographic method using UV absorption was
      developed for determining moniliformin in corn. The toxin was extracted with
      water containing 1% tetrabutylammonium hydrogen sulfate (w/v). Paired
      moniliformin was partitioned into dichloromethane, which was evaporated to
      dryness at 50 degrees C. The residue was dissolved in water and applied to a
      disposable strong-anion exchange solid-phase extraction tube. Adsorbed
      moniliformin was eluted from the tube with 0.05M sodium dihydrogen phosphate
      monohydrate (pH 5). It was determined by ion-pair reversed-phase chromatography
      and UV measurement at 229 nm. The minimum detectable amount of pure moniliformin
      was 0.25 ng/injection (signal-to-noise ratio = 3:1). The detector response was
      linear from 0.25 to at least 20 ng. The limit of determination was 0.025
      microgram/g corn. Recoveries of moniliformin from corn spiked at 0.025, 0.05,
      0.25, and 1.0 microgram/g averaged 96.5, 96.2, 97.2, and 97.8% respectively.

PMID- 9772743
TI  - Rapid determination of volatile bases in fish by using an ammonia ion-selective
      electrode.
AB  - A simple and rapid method using an ammonia ion-selective electrode (ISE) to
      measure volatile bases in fish is proposed. Accuracy and precision were
      determined with 5, 10, 20, and 30 ppm NH3 standard solutions. Ammonia values
      obtained with the method correlate strongly with total volatile basic nitrogen
      (r2 = 0.88). Recoveries of added ammonia to homogenized fish samples ranged from
      83.7 to 96.0%. Responses of the probe to trimethylamine (TMA), calculated as NH3
      (mg/100 mL), ranged from 74.9 to 91.7%. These findings indicate that the probe
      measured TMA as well as ammonia. Storage trials on 8 fish species illustrated
      that the results obtained with the ISE method reflected nitrogen concentrations
      based on total volatile base (TVB) analysis. This procedure may be used in lieu
      of the traditional TVB method for on-site rapid screening of fish.

PMID- 9772744
TI  - Determination of malathion residues in some medicinal plants by liquid
      chromatography with gas chromatographic/mass spectrometric confirmation.
AB  - A method for determining malathion residues by reversed-phase liquid
      chromatography (LC) using methanol only as mobile phase is described. Malathion
      [diethyl(dimethoxyphosphinothiol)succinate] was applied on marjoram, mint, and
      chamomile. Residues were detected in fresh and dry crops by LC and confirmed by
      gas-LC/mass spectrometry. Average recovery of malathion was 85%. Residues
      detected in fresh marjoram, mint, and chamomile were 0.18, 0.23, and 0.083 mg/kg,
      respectively. Residues detected in dry marjoram and mint were 0.024 and 0.050
      mg/kg, respectively. No malathion residues were detected in dry chamomile. The
      minimum detectable concentration with this method is 0.013 mg/kg. The study
      suggests it is safe to use malathion up to 2 sprays per season provided the crop
      is harvested not less than 3 weeks from the last spray.

PMID- 9772745
TI  - Gel permeation and florisil chromatographic cleanup and gas chromatographic
      determination of organochlorine pesticides in eggs.
AB  - Cleanup of residual organochlorine pesticides (OCPs; alpha-, beta-, gamma-, and
      delta-BHC; aldrin; dieldrin; p, p'-DDE; o,p'-DDT; p,p'-DDD; and p,p'-DDT) in eggs
      by gel permeation chromatography (GPC) and Florisil minicolumn chromatography is
      described. Ten OCPs in purified extract are determined by gas chromatography with
      electron capture detection. The lipids extracted from whole egg are cleaned up
      first by GPC with an Envirogel column and an ethyl acetate-cychlohexane (1 + 1,
      v/v) mobile phase and then by Florisil minicolumn chromatography with 15% (v/v)
      diethyl ether-hexane eluant. Cleanup is highly efficient. Average recoveries of
      10 spiked OCPs (0.0025-0.0125 ppm) ranged from 81 to 101%, with coefficients of
      variation between 1 and 14%. The detection limit was 0.001 ppm for the 10 OCPs.

PMID- 9772746
TI  - Liquid chromatographic determination of five benzoylurea insecticides in fruit
      and vegetables.
AB  - A liquid chromatographic (LC) method was developed to determine 5 benzoylureas-
      diflubenzuron, hexaflumuron, teflubenzuron, flufenozuron, and lufenuron--in
      peppers, tomatoes, eggplants, cucumbers, and oranges. Preparation of samples
      involve extraction with acetone and partitioning into dichloromethane-petroleum
      ether. A portion of this extract is cleaned up with a solid-phase extraction
      aminopropyl disposable column. With LC analysis using an RP-8-DB microbore
      column, acetonitrile-water (70 + 30, v/v) as mobile phase, and photodiode array
      detection at 254 nm, recovery and repeatability data were collected for the 5
      benzoylureas on 4 vegetables and citrus in the range 0.04-2.0 mg/kg. Validated
      limits of detection and quantitation were 0.01 and 0.04 mg/kg, respectively. The
      method is reliable for routine analysis of vegetables and fruits.

PMID- 9772747
TI  - Determination of chromium in wine and other alcoholic beverages consumed in spain
      by electrothermal atomic absorption spectrometry.
AB  - A reliable and rapid method is described for the determination of chromium in
      alcoholic beverages by electrothermal atomic absorption spectrometry (ETAAS)
      after optimization of the temperature-time program for the graphite furnace.
      Chromium in wines was determined directly without sample pretreatment. Other
      samples were first mineralized with HNO3 and V2O5. The method was validated, and
      its analytical characteristics were checked. The detection limit was 1 pg (for a
      sample volume of 10 microL). Accuracy was 99.20 +/- 3.80% for wines and 98.90 +/-
      2.00% for other beverages. Precision ranged from 3.50 to 4.50%. The proposed
      method was applied to 124 samples of alcoholic beverages frequently consumed in
      Spain. Mean values obtained (microgram/L) were 20.28 for wines, 8.75 for beer,
      7.85 for cider, 14.60 for brandy, 7.50 for rum, 10.25 for whisky, 8.80 for gin,
      9.25 for vodka, 24.45 for anisette, and 10.08 for liquors. The advantages of the
      proposed method (rapidity, sensitivity) and versatility) make it useful for
      routine analyses and for estimations of dietary intake of chromium.

PMID- 9772748
TI  - Determination of phenylurea herbicide residues in vegetables by liquid
      chromatography after gel permeation chromatography and Florisil cartridge
      cleanup.
AB  - A liquid chromatographic method for quantitative determination of 9 phenylurea
      herbicide residues (metoxuron, metobromuron, monolinuron, chlortoluron,
      isoproturon, diuron, linuron, chloroxuron, and neburon) in potatoes, carrots, and
      mixed vegetables is described. Samples are extracted with acetone, partitioned
      with ethyl acetate-cyclohexane (50 + 50, v/v) and cleaned up by gel permeation
      chromatography with ethyl acetate-cyclohexane (50 + 50, v/v) as eluant. A small
      column (1 cm id) packed with Biobeads SX3 resin is used to reduce solvent
      consumption and analytical time. After solid-phase extraction on a Florisil
      cartridge, herbicide residues are successfully separated on a C18 column by
      gradient elution and determined by UV detection at 242 nm. Average recoveries of
      9 compounds from different samples range from 70 to 98% at 0.010 and 0.100 mg/kg
      fortification levels. Quantitation limits are 0.010 mg/kg.

PMID- 9772749
TI  - Characterization of balsamic vinegar by multivariate statistical analysis of
      trace element content.
AB  - To characterize vinegars according to the types prescribed by Italian
      regulations, 8 trace elements (Cr, Mn, Co, Ni, Cu, Zn, Cd, and Pb) were
      determined. The data collected were successively elaborated by 3 statistical
      techniques: linear principal component analysis (LPCA), linear discriminant
      analysis (LDA), and cluster analysis (CA). LDA and LPCA best classified and
      discriminated the 3 types of vinegar under study, separating traditional balsamic
      vinegars from the other 2 types, nontraditionally aged balsamic vinegars and
      common vinegars. The latter 2 types were appreciably distinguished only by LDA
      through bidimensional analysis of discriminant scores.

PMID- 9772750
TI  - Measurement of volumetric (OUR) and determination of specific (qO2) oxygen uptake
      rates in animal cell cultures.
AB  - Oxygen is a key substrate in animal cell metabolism. It has been reported that
      the oxygen uptake rate (OUR) is a good indicator of cellular activity, and even
      under some conditions, a good indicator of the number of viable cells. The
      measurement of OUR is difficult due to many different reasons. In particular, the
      very low specific consumption rate (0.2 x 10(-12) mol cell h-1), the sensitivity
      of the cells to variations in dissolved oxygen concentration and the difficulty
      to provide oxygen without damaging the cells are problems which must be taken
      into account for the development of OUR measurement methods. Different solutions
      based on an oxygen balance on either the liquid phase or around the entire
      reactor, and with a variable or stable concentration of dissolved oxygen have
      been reported. The accuracy of the OUR measurements and the required analytical
      devices are very different from method to method.

PMID- 9772751
TI  - Fluorescence cross-correlation: a new concept for polymerase chain reaction.
AB  - In this article we present a new concept for the detection of any specifically
      amplified target DNA sequences in multiple polymerase chain reactions (PCR) based
      on fluorescence correlation spectroscopy (FCS). The accumulation of double
      stranded target DNA is monitored by the cross-correlated fluorescence signals
      provided by two amplification primers which are 5'-tagged with two different
      kinds of fluorophores (Rhodamine-Green and Cy5). Only the amplified target DNA
      sequence carrying both primers is observed. Its signal emerges from the
      background of non-incorporated or non-specifically incorporated primers. Down to
      10-25 initial copy numbers of the template in the PCR compartment DNA can
      presently be detected. No external or internal standards are required for
      determining the size and the amplified copy number of specific DNA. The PCR
      amplification process is started with all ingredients in a single compartment
      (e.g. of a microtiter plate), in which amplification and measurement are
      performed. This eliminates the need for post-PCR purification steps. The
      homogeneous one-tube approach does not depend on fluorescence energy transfer
      between the fluorogenic dyes. Thus, it does not interfere with the enzymatic
      amplification reaction of PCR and allows the continued use of different
      conditions for amplifying DNA. The results exemplified by PCR-amplified 217-bp
      and 389-bp target DNA sequences demonstrate that the analysis based on two-color
      fluorescence cross-correlation is a powerful method for simplifying the
      identification of targets in PCR for medical use. For this purpose, an instrument
      optimized for two-color excitation and detection of two-color emission has been
      developed, incorporating the principle of confocal arrangement.

PMID- 9772752
TI  - Aberrant processing of wild-type and mutant bovine pancreatic trypsin inhibitor
      secreted by Aspergillus niger.
AB  - Bovine pancreatic trypsin inhibitor (BPTI) was secreted by Aspergillus niger at
      yields of up to 23 mg l-1 using a protein fusion strategy. BPTI was linked to
      part of the fungal glucoamylase protein (GAM) with a dibasic amino acid (KEX2)
      processing site at the fusion junction. Electrospray ionisation mass spectrometry
      and N-terminal protein sequencing revealed that, although biologically active in
      vitro, the purified products from a number of independent transformants consisted
      of a mixture of BPTI molecules differing at the N-terminus. Approximately 35-60%
      of this mixture was processed correctly. Aberrant processing of the GAM-BPTI
      fusion protein by the A. niger KEX2-like endoprotease was the most likely cause
      of this variation although the involvement of other fungal endoproteases could
      not be ruled out. In vitro studies have highlighted a weak interaction between
      BPTI and the Saccharomyces cerevisiae KEX2 endoprotease, suggesting that BPTI is
      not a potent inhibitor of KEX2p. A small proportion of the recombinant BPTI (10%)
      showed 'nicking' of the K15-A16 bond, indicating an interaction with a fungal
      trypsin-like enzyme. Mutant BPTI homologues designed to have anti-elastase
      activity, BPTI(K15V), BPTI(K15V,P13I) and BPTI(K15V,G12A), have also been
      expressed and secreted by A. niger. They also showed a similar spectrum of
      aberrant N-terminal processing but no 'nicking' of the K15-V16 bond was observed.
      Comparison of A. niger with other expression systems showed that it is an
      effective system for producing BPTI and its homologues, although not all
      molecules were correctly processed. This variation in processing efficiency may
      be useful in understanding the important determinants of protein processing in
      this fungus.

PMID- 9772754
TI  - Rapid and highly automated determination of adenine and pyridine nucleotides in
      extracts of Saccharomyces cerevisiae using a micro robotic sample preparation
      HPLC system.
AB  - An ion-pair reversed-phase chromatography method was adapted for the simultaneous
      separation and quantification of adenine and pyridine nucleotide concentrations
      in cell extracts of Saccharomyces cerevisiae. Microbial extracts including
      metabolites, macromolecular constituents and inorganic compounds were loaded onto
      a ODS pre-column in the presence of triethylamine phosphate (TEA-Pi) resulting in
      a selective binding of the nucleotides and removing of interfering compounds.
      After washing the enrichment cartridge with 30 mM TEA-Pi buffer, adenine and
      pyridine nucleotides were eluted with a gradient of Mg(II), the competing
      hetaeron. This combined cleaning and concentration step leads to remarkable
      improvement of the detection limit for all nucleotides of interest and column
      lifetimes. The clean up and separation procedures were performed automatically
      with a micro robotic-system and a control software package written in PASCAL. The
      paper reports about the application of the proposed method to separation of
      adenine and pyridine nucleotides in cells extracts of S. cerevisiae grown
      anaerobically in a continuous culture (D = 0.1 h-1). Rapidity of analysis, high
      sensitivity as well as reproducibility of the system and the accurate evaluation
      of the adenine and pyridine nucleotide concentrations make this method
      particularly useful for routine analysis.

PMID- 9772753
TI  - Rapid monitoring of virus-like particles using an optical biosensor: a
      feasibility study.
AB  - Virus-like particles (VLPs) are multimeric proteins expressed by Saccharomyces
      cerevisiae. The particles are approximately 80 nm in diameter and they are used
      as a framework for a range of biological products; for example as carriers of
      viral antigens. Rapid monitoring of purified VLPs was investigated using an
      optical biosensor. The aim was to develop an assay which may be employed for real
      time bioprocess monitoring of VLPs. Problems of mass transfer of analyte were
      overcome through selection of a planar biosensor surface, in preference to the
      traditional polymer-coated surface. To prolong the surface activity for
      interaction analysis, a sandwich assay was developed which involved the use of a
      secondary capture species. It was shown that VLP concentration in pure solution
      could be determined within 10 min.

PMID- 9772755
TI  - Beyond hearing loss.

PMID- 9772756
TI  - Are your workers protected to deaf?

PMID- 9772757
TI  - Instant gratification.

PMID- 9772758
TI  - Drugs in the workplace.

PMID- 9772759
TI  - Up on the roof.

PMID- 9772760
TI  - Serving up food safety.

PMID- 9772761
TI  - Controlling silica exposures.

PMID- 9772762
TI  - Global protection.

PMID- 9772763
TI  - Surviving old man winter.

PMID- 9772764
TI  - Ejection of neutral molecules from ion-bombarded organic surfaces.
AB  - Time-of-flight distributions of neutral molecules ejected from various organic
      surfaces have been measured subsequent to 8 keV Ar+ and H2+ ion bombardment. The
      distributions show that depending on the physical and chemical nature of the
      substrate, the neutral molecules have strikingly different desorption profiles.
      For C6H6/Ag?111?, at low coverage the C6H6 molecules eject with energies in the
      range 0.25-1 eV while at high coverage most of the molecules desorb with thermal
      kinetic energies (approximately 0.04 eV). At intermediate coverage two peaks are
      present in the time-of-flight distribution indicating that two different
      mechanisms contribute to the desorption process. For self-assembled monolayers of
      phenylethanethiol on Au, while a minor ejection is observed at higher kinetic
      energy (approximately 1 eV) most of the molecules desorb with thermal kinetic
      energies (approximately 0.03 eV). Pyrenebutyric acid molecules ejected from
      monolayer and multilayer samples have kinetic energies close to 0.2 eV. One
      ejection mechanism is observed in this case. For tryptophan, most molecules eject
      with kinetic energies close to 0.1 eV. In addition, a feature unique to this case
      is the continuous emission of molecules from the surface that extends beyond 200
      microseconds after ion impact. For all the multilayer samples investigated, a
      molecular collision cascade in the solid leads to ejection of molecules with
      kinetic energies in the range 0.1-0.3 eV.

PMID- 9772765
TI  - Static time-of-flight secondary ion mass spectrometry imaging of freeze
      fractured, frozen-hydrated biological membranes.
AB  - The study of cell membrane lipid and steroid composition and distribution is
      important for the understanding of membrane dynamics and function. Here we
      present efforts to chemically image phospholipid distributions on a submicron
      scale on freeze-fractured and frozen-hydrated liposomes and red blood cells using
      time-of-flight secondary ion mass spectrometry. Sample preparation by freeze
      fracturing of membranes is described. Fragments representative of phospholipid
      headgroups are found to be localized on both liposomes and red blood cells. In
      addition, the cholesterol molecular ion [M + H] is localized on liposome
      surfaces.

PMID- 9772766
TI  - Vacuum ultraviolet single photon versus femtosecond multiphoton ionization of
      sputtered germanium clusters.
AB  - Neutral atoms and clusters desorbed from a solid germanium surface by ion
      bombardment are detected by laser postionization and time-of-flight mass
      spectrometry. Two different photoionization schemes are compared which are
      generally believed to be candidates for the 'soft' ionization of polyatomic
      species without significant photon induced fragmentation. First, a single photon
      ionization process is employed using an F2 laser as an intense VUV source with a
      photon energy in excess of all relevant ionization potentials. It is shown that
      the available laser pulse energy is sufficient to saturate the ionization of Ge
      atoms and all detected Ge(n) clusters. The resulting mass spectra are compared to
      those obtained with a non-resonant multiphoton ionization process using a high
      intensity laser delivering pulses of 250 femtoseconds duration at a wavelength of
      267 nm. Also in this case, the ionization process can apparently be driven into
      saturation. The mass spectra measured under these conditions are found to be
      almost identical to those obtained using single photon ionization. We take this
      as an indication that the results obtained with both postionization techniques
      closely reflect the true cluster sputtering yields and, in particular, are not
      dominated by photon induced fragmentation.

PMID- 9772767
TI  - Performance characteristics of a chemical imaging time-of-flight mass
      spectrometer.
AB  - A chemical imaging time-of-flight secondary ion mass spectrometer is described.
      It consists of a liquid metal ion gun, medium energy resolution reflectron mass
      analyzer, liquid nitrogen cooled sample stage, preparation chamber and dual stage
      entry port. Unique features include compatibility with laser postionization
      experiments, large field of view, cryogenic sample handling capability and high
      incident ion beam current. Instrument performance is illustrated by the
      characterization of scanning electron microscopy grids, silver and functionalized
      polystyrene beads and the postionization of an organic overlayer on a gold
      substrate.

PMID- 9772768
TI  - Postionization of molecules desorbed from surfaces by keV Ion bombardment with
      femtosecond laser pulses.
AB  - We report the use of femtosecond laser photoionization of sputtered neutral
      molecules to enhance the sensitivity of detection and to improve the prospects
      for molecule-specific imaging experiments. Results are presented for patterned
      metal oxides, polycyclic aromatic hydrocarbons and several amino acids. In
      addition to increased signal levels, we find that is photoionization generally
      yields simpler mass spectra than the corresponding SIMS spectra, although
      considerable fragmentation is observed in both cases.

PMID- 9772770
TI  - [The meeting between patient and physician can be of decisive importance. Large
      fields of research are still untouched when it comes to this relation which is
      difficult to study].

PMID- 9772771
TI  - [Mentally disabled--an old-fashioned concept. Comment on the report on
      involuntary commitment].

PMID- 9772769
TI  - [Too much alarm about cadmium? The risk of epidemics of cadmium-induced renal
      failure is there, but it is a minor risk].

PMID- 9772772
TI  - [If the 18th century new, it would have laughed at us].

PMID- 9772773
TI  - [Listen to Cochrane too!].

PMID- 9772774
TI  - [Dental work with amalgam fillings during pregnancy is not without risks].

PMID- 9772775
TI  - [Laparoscopic button is a safe method in pediatric gastrostomy].

PMID- 9772776
TI  - [Choose preparations that affect the intestinal ecosystem as little as
      possible!].
AB  - The administration of antimicrobials often causes ecological disturbances in the
      normal microflora, such as decreased colonisation resistance which may result in
      overgrowth of potentially pathogenic micro-organisms such as yeasts and
      Clostridium difficile. Another possible consequence is the establishment of
      resistant strains which may spread within the host, or from person to person,
      causing infection. Resistant bacteria can also transfer resistance genes to their
      own or other species. The article consists in a review of studies performed by
      various investigators during the past 20 years, and illustrating the impact of
      different antimicrobial agents on the human gastrointestinal microflora.

PMID- 9772777
TI  - [Antibiotic resistance here to stay? Compensatory mutations restore virulence of
      resistant bacteria].
AB  - Bacterial antibiotic resistance has increased alarmingly because of overuse of
      antibiotics both in humans and animals. One way of reversing this development is
      to reduce the use of antibiotics, thus promoting the disappearance of the
      resistant bacteria already present in humans and the environment. This approach
      is based on the assumption that resistance is conferred at the cost of impaired
      survival fitness in the absence of antibiotics, as compared with sensitive
      strains. It seems to be generally true that resistant bacteria are less fit than
      the respective sensitive strains, which suggests that resistance may be
      reversible. However, a complicating factor is the frequent finding in resistant
      strains of various types of compensatory mutations that restore fitness without
      concomitant loss of resistance. Thus, second-site compensatory mutations may
      allow resistant strains to persist and compete successfully with sensitive
      strains even in an environment depleted of antibiotics. It is concluded in the
      article that, if compensatory mutations are as common in clinical settings as
      they are in the laboratory, many types of resistance will be irreversible.

PMID- 9772778
TI  - [A hypothesis based on animal experiments: pain in newborn infants indicates pain
      reaction in adulthood].

PMID- 9772780
TI  - ["Medical scandal of the century". What can be learned in the future from the
      Bristol experiences?].

PMID- 9772779
TI  - [Reduced level of cadmium in the renal cortex. Due to less smoking or
      environmental improvement?].
AB  - A cross-sectional study of the renal cortex cadmium concentrations in 171 cases
      of sudden death showed the levels to be lower than those quoted m a Swedish
      report published in 1976 the reduction being more than 50 per cent among the < or
      = 40-year-old age group. The reduction is probably attributable to reduced
      smoking among. Swedes during the past few decades, though there were indications
      of reduced cadmium levels in non-smoking as well.

PMID- 9772781
TI  - [Legg-Calve-Perthes disease--a mysterious hip joint disease in children.
      Diagnosis, investigation and treatment].
AB  - The major challenge to the attending physician in cases of children with Legg
      Calve-Perthes disease (LCPD) is to prevent the development of degenerative
      arthritis of the hip joint. In the presence of unfavourable prognostic factors
      such as lateral subluxation or more than 50 per cent necrosis of the femoral
      head, the examination should be complemented by MRI (magnetic resonance imaging),
      and operative treatment be considered. Treatment is commonly based on the
      principle of containment of the femoral head to prevent its deformity. However,
      there is no consensus as to the treatment of LCPS, and as the aetiology remains
      unknown the optimal treatment is similarly unclear.

PMID- 9772782
TI  - [Georg Perthes--an all-round pioneer in surgery. Remembered for a pediatric
      orthopedic disease].

PMID- 9772784
TI  - [When salicylates do not help. Practice in recurrent TIA (Transient Ischemic
      Attack) varies at Swedish hospitals].

PMID- 9772785
TI  - [Endotoxin kan reduce the level of antibodies against lipopolysaccharides. A case
      report on reactive arthritis following Salmonella virchow infection].

PMID- 9772786
TI  - [Agreement between physician and patient. A way to consider the physician-patient
      meeting].

PMID- 9772783
TI  - [A new risk pattern of coronary disease is alarming. Increased body weight
      threatens the positive trend].

PMID- 9772787
TI  - [The first extensive study in Sweden: 50,000 persons addicted to gambling, more
      often among the younger].

PMID- 9772788
TI  - [The WHO in the future--what can or must be done?].

PMID- 9772789
TI  - [Hypothyroidism--a common disease with many faces. Thyroid function in women
      should be regularly examined].

PMID- 9772790
TI  - [Increased responsibility of school health services! The school health physician
      should be a natural co-operator for the teachers].

PMID- 9772791
TI  - [Stem cells can be reprogrammed soon. Increasing knowledge on signals which
      direct the formation of CNS].

PMID- 9772792
TI  - [Internal medicine is a natural base for emergency medicine specialization].

PMID- 9772793
TI  - [Problems after whiplash injuries are seldom chronic].

PMID- 9772794
TI  - [No health care without physicians].

PMID- 9772795
TI  - [Alcohol as a disinfectant resulted in zero per thousand in blood].

PMID- 9772796
TI  - [Time to abolish the poly/mono concept in blood].

PMID- 9772797
TI  - [Philosophy of sports medicine and principles for handling].

PMID- 9772798
TI  - [Reduced morbidity and the risk of premature death. Regular physical exercise is
      beneficial for health at all ages].
AB  - Regular physical activity yields benefits to men and women of all ages. The risk
      of premature death is reduced, as is that of incurring or dying of ischaemic
      heart disease. These benefits are attainable with only moderate physical
      activity, such as a 30-minute daily walk, though a "dose-dependent" relationship
      exists between physical activity and health benefits: "Some exercise is better
      than none, and more is better than less". Both the World Health Organisation, and
      the National Institutes of Health in the USA, for example, recommend that
      clinicians should counsel all patients to enroll in some programme of regular
      physical activity tailored to suit their health status and personal life-style.

PMID- 9772799
TI  - [Renal artery stenosis--an underestimated cause of hypertension and renal
      failure?].
AB  - Although renovascular hypertension is associated with substantial cardiovascular
      morbidity, ultimately it is a curable disease. Early identification and
      appropriate treatment of renovascular hypertension may save years of
      antihypertensive therapy, reduce the morbidity associated with long-standing
      hypertension, and help to minimise the risk of renal failure. However, the main
      problem is to identify patients with renovascular disease suitable for treatment.
      This requires alertness in the clinician, and renographic screening of renal
      function or duplex-ultrasound scanning of renovascular circulation to augment the
      yield of angiographic procedures. The predominant treatment of renovascular
      disease today is percutaneous transluminal angioplasty, which can be used as a
      repeat procedure or in combination with endoluminal stenting of the stenotic
      renal artery.

PMID- 9772800
TI  - [Spectrum of sequelae after whiplash injury. Localization and development in
      relation to the clinical picture].
AB  - Neck sprain, a common sequela of motor vehicle trauma, is characterised by soft
      tissue lesions in the facet joints (the capsule), cervical discs (the annulus),
      ligaments, muscles, and sometimes in the nerve roots or the central nervous
      system. The cardinal manifestation of whiplash injury is neck pain, which may
      arise from any innervated part of the injured joints or muscles except the disc
      nucleus, the articular surface of facet joints, or the flaval ligaments. Pain may
      be referred to the skin or muscles via the respective sensory nerves. The tissue
      lesions, together with post-traumatic nerve root degeneration or medullary
      compression, may give rise to the complex neck sprain syndrome. Localisation of
      the source of symptoms by means of meticulous physical examination, MRI (magnetic
      resonance imaging), or accurately sited local anaesthetic injections is described
      in the article, and operative and multimodal rehabilitation procedures are
      discussed.

PMID- 9772801
TI  - [My grandfather worked as a psychiatric aid at the Birgitta Hospital in
      Vadstena].

PMID- 9772802
TI  - [Biliary reflux can be a contributory cause of esophagitis].
AB  - In recent years duodenogastric reflux has been recognised as a possible cause of
      oesophagitis. Alone or in combination, bile salts, trypsin, pepsin, and
      hydrochloric acid have all been shown to cause oesophagitis. Duodenal content in
      the oesophagus can be measured by means of a new fibre-optic sensor, Bilitech
      2000, a device measuring the occurrence of bilirubin and yielding 24-hour
      readings from the distal oesophagus. Studies in which the device has been used
      have shown oesophageal bilirubin to be increased in patients with oesophagitis,
      especially in the subgroup with such complications as oesophageal stricture or
      ulceration, or Barrett's oesophagus. The evidence suggests that unsatisfactory
      response to proton pump inhibitors in reflux patients might be due to an increase
      in duodenal reflux, and should be treated surgically with fundoplication or
      biliary diversion. This may also be true of oesophagitis patients with
      complications, though this remains to be shown in clinical studies.

PMID- 9772803
TI  - [Hypothyroidism--clinical findings, diagnosis, therapy. Thyroid tests should be
      performed on broad indications].
AB  - Hypothyroidism is a clinical entity resulting from deficiency of thyroid hormones
      or, more rarely, from their impaired activity at tissue level. It is a common
      condition, with a prevalence of 1.9 per cent in women, and the prevalence
      increases with age. Hypothyroidism may be congenital or acquired, primary or
      secondary, chronic or transient. Primary hypothyroidism is caused by disease or
      treatment which destroys the thyroid gland or interferes with thyroid hormone
      biosynthesis. Autoimmune thyroiditis is the predominant cause of primary
      hypothyroidism in countries such as Sweden where severe iodine deficiency is non
      existent. Another cause of primary hypothyroidism, chronic or transient, is
      previous radio-iodine or surgical treatment of hypothyroidism. In secondary or
      central hypothyroidism, which is very rare, there is a lack of thyroid
      stimulating hormone (TSH) or TSH activity, due to a pituitary or hypothalamic
      cause. The clinical features of hypothyroidism are dependent on the patient's
      age, the presence of other disease, and the rate at which hypothyroidism
      develops. As thyroid hormones are universal determinants of organ function, there
      may be a multiplicity of symptoms. Particularly in the elderly, the clinical
      features may be atypical, and the diagnosis easily missed. First line tests for
      hypothyroidism are analyses of the concentrations of free thyroxine (T4) and TSH
      in serum. In primary hypothyroidism, the serum content of T4 is low and that of
      TSH high. In central hypothyroidism, the serum content of T4 is low and that of
      TSH generally low or normal, though slightly increased levels of biologically
      inactive TSH may also occur. Subclinical hypothyroidism is characterised by a
      normal serum level of T4, an increased level of TSH, and the absence of clinical
      symptoms. When a diagnosis of chronic hypothyroidism is confirmed, treatment with
      laevothyroxine is started, the initial dose being adjusted to the age and general
      condition of the patient, and the duration and severity of hypothyroidism. As a
      rule, full thyroxine replacement therapy should bring the serum TSH level into
      the normal range. In central hypothyroidism, laevothyroxine treatment is similar,
      but pituitary function must be evaluated and, if necessary, corticosteroid
      replacement be instituted before laevothyroxine treatment is started.

PMID- 9772804
TI  - [Remodelling of connective tissue of the cervix during pregnancy. An important
      process for labor onset and progress].

PMID- 9772805
TI  - [Child health centers do not catch all preschool children with problems. Child
      health services should co-operate with school health services more closely].

PMID- 9772806
TI  - [Thrombosed pacemaker lead may have been the cause of cerebral embolism].

PMID- 9772808
TI  - [Can preventive health care be defined?].

PMID- 9772807
TI  - [Physician's hands--typical and magic].

PMID- 9772809
TI  - [Latex allergy--an increasing problem].

PMID- 9772810
TI  - [Technology under the skin].

PMID- 9772811
TI  - [Continuous intrathecal infusion of baclofen. A new therapeutic method for
      spasticity].
AB  - Intrathecal administration of baclofen is now generally accepted as a powerful
      treatment of spasticity caused by spinal lesions. 35 patients with severe
      spasticity, 29 of spinal origin and six of supraspinal origin resistant to
      conservative treatment, had a programmable pump (Synchromed, Medtronic) for
      continuous intrathecal baclofen infusion implanted. The patients were followed-up
      for an average of 29 months (0-68). The initial effect of the treatment was
      positive for all patients; spasms were less frequent, there was remission of pain
      caused by cramps, and in some cases improved ambulation. In five patients,
      however, the pump was later removed: in two patients the pump ceased to be
      effective, two patients became infected, and one experienced multiple catheter
      problems. Problems with the catheter was the most common complication
      experienced, and this was seen in nine patients. Three patients died of the
      underlying disease. The majority of patients became accommodated to intrathecal
      baclofen and it was necessary to administer increasingly larger doses to maintain
      the clinical effect. Long-term control of spinal spasticity by intrathecal
      baclofen can be achieved in most patients, but close follow-up is necessary for
      assessing efficacy and refilling the pump.

PMID- 9772812
TI  - [Breast conserving surgery for breast cancer--local recurrence].
AB  - One of the disadvantages of breast conserving treatment compared with mastectomy
      is the higher rate of local recurrence. Even though a local recurrence has no
      influence on survival, it is a psychological trauma for the woman it affects.
      Breast conserving treatment has been practised at Ullevaal Hospital since 1986.
      This study is based on data from 216 consecutive cases of breast conserving
      surgery, from January 1986 to March 1996. Mean observation time was 29 months.
      Nine (4.2%) patients experienced a local recurrence. Age, histological grade, and
      the size of the tumor were identified as risk factors, whereas there was no
      correlation between histology, axillary node involvement, and surgical margins.

PMID- 9772813
TI  - [Diagnosis and treatment of obstructive lung diseases].
AB  - Obstructive pulmonary disease can be divided into bronchial asthma and chronic
      obstructive pulmonary disease. Using a questionnaire, we carried out a survey
      among doctors in Hordaland county in order to discover how they diagnosed and
      treated obstructive pulmonary disease. The response rate was 60%; 119 general
      practitioners and 48 hospital doctors. In spite of recommended guidelines, 20% of
      the doctors did not perform any kind of spirometry when diagnosing obstructive
      pulmonary disease. Spirometry after inhalation of bronchodilators or
      corticosteroids was performed by 29% of the doctors when diagnosing chronic
      obstructive pulmonary disease and by 43% when diagnosing asthma. 88% of the
      doctors who participated in our survey preferred to treat asthma with inhalation
      of beta-agonist or inhalation of corticosteroids, or both. This was in accordance
      with recommended guidelines. There was greater uncertainty amongst the doctors
      concerning the treating of chronic obstructive pulmonary disease, and the
      guidelines were followed to a lesser extent.

PMID- 9772814
TI  - [The POEMS syndrome--a rare multiorgan disease].
AB  - POEMS syndrome is a rare multisystemic disorder characterized by a variable
      constellation of polyneuropathy, organomegaly, endocrinopathy, monoclonal
      gammopathy and skin changes. The syndrome is believed to be immune-mediated and
      is probably related to the pathological monoclonal component caused by a myeloma
      or a plasmocytoma. The treatment is aimed at the underlying plasma cell
      dyscrasia. We have studied three patients with this rare syndrome. This article
      presents the clinical picture of each one and a survey of the literature.

PMID- 9772816
TI  - [Tropical pyomyositis].
AB  - Tropical pyomyositis is rarely observed among permanent residents of temperate or
      cold climates and is, to our knowledge, not described among Norwegians. It is a
      clinical entity comprising general symptoms of infection and abscesses in
      skeletal muscles. We present one case of tropical pyomyositis acquired in the
      Dominican Republic. The patient, a female, had an insidious progression of the
      disease with fever, chills, and general malaise. On admission she had also
      developed multiple abscesses affecting muscles of the extremities. She required
      surgical drainage in addition to antibiotics. Cultures from purulent material
      revealed Staphylococcus aureus.

PMID- 9772815
TI  - [Cytomegalovirus as the cause of toxic dilatation of the colon].
AB  - Toxic dilatation of the colon is sometimes a complication which occurs during
      exacerbations of inflammatory bowel disease. It often requires immediate surgical
      intervention. We describe here a male patient with known ulcerative colitis who
      was investigated for fever of unknown cause, diarrhoea, and general illness. Upon
      admission he had only modest symptoms of colitis and received no
      immunosuppressive treatment. The condition worsened considerably, and subsequent
      colonoscopy demonstrated widespread lesions compatible with viral disease, but
      not with ulcerative colitis. Antiviral treatment for cytomegalovirus was started
      immediately, but progression of the condition with toxic dilatation called for a
      rapid colectomy. Histological examination showed widespread lesions compatible
      with cytomegalovirus infection. This clinical picture is rarely seen in
      immunocompetent patients.

PMID- 9772817
TI  - [Latex contact urticaria and prick test with latex extract].
AB  - Latex contact urticaria is being reported with increasing frequency. Atopic
      patients with dermatitis of the hands are at risk of developing this potentially
      life threatening allergy. Since 1994 we have tested 200 patients in our
      dermatological department using the latex skin prick test. 20 relevant, positive
      latex tests have been found. Glove tests and latex-RAST were performed where
      these were indicated. The diagnosis of latex contact urticaria would have been
      overlooked in nine patients had the latex prick test not been performed. The
      clinical manifestations and findings in 24 patients with latex contact urticaria
      are presented. 12 out of 20 adult patients were not in jobs related to health
      care. All adults were female, but among the children there were three boys.

PMID- 9772818
TI  - [Prevention of work-related latex allergy].
AB  - Latex allergy has become a common work-related disease among health care workers.
      An increase in the use of latex gloves is the main reason for this. Measures to
      prevent sensitization and allergic reactions to latex can be implemented at
      various administrative levels: at national and international levels by
      regulations and recommendations, and by the implementation of various measures at
      the place of work. When to use gloves and what gloves to use are important
      issues, balancing barrier properties and the need to prevent infection with the
      need to prevent sensitization and allergic reactions to latex. There are great
      variations between allergen levels in different gloves, and this can be measured
      in different ways. Threshold levels are not specified, and latex gloves should
      not be considered devoid of allergenic potential. The Norwegian Labour Inspection
      Authority has carried out a survey on latex gloves, based on information from
      manufacturers and importers, and present this survey to guide glove users. We
      recommend powder-free gloves with low levels of latex allergens/leachable
      proteins, chemicals and endotoxins. There are several low-allergen gloves
      available on the Norwegian market, but for some gloves we lack important
      information.

PMID- 9772819
TI  - [Two patients with chlorhexidine allergy--anaphylactic reactions and eczema].
AB  - A 14 year-old girl experienced a combined delayed and immediate type of allergy
      to chlorhexidine. She first developed an eczematous reaction in the face
      following the long-term application of an antiacne preparation. Use test
      (repeated Open Application Test, ROAT) on the forearm was positive. Epicutaneous
      tests with 1% chlorhexidine gluconate and acetate were both positive. About six
      months later she developed an urticarial rash and syncope after cleansing the
      skin with chlorhexidine gluconate. Prick tests were positive to 0.05%
      chlorhexidine gluconate and to 0.01% of the acetate solution. A 30 year-old man
      developed anaphylactic symptoms following treatment with an antiseptic dental gel
      containing 1% chlorhexidine gluconate. Prick test was positive to the gel and to
      chlorhexidine gluconate 0.5%.

PMID- 9772820
TI  - [Norwegian dietary habits--from low-fat poverty food to low-fat welfare food].
AB  - Norwegian society has undergone major changes in the 20th century, also with
      regard to its dietary habits. During the first half of the century dietary
      changes were characterised by a substantial decrease in the consumption of
      cereals and an increase in the use of margarine and other foods rich in fat. In
      the past 30 years there has been a major decrease in the consumption of potatoes,
      margarine and butter, a change from fatty to skimmed types of milk, and an
      increase in the consumption of fruit, vegetables, meat, cheese, fatty snacks, and
      soft drinks. These changes were responsible for a rise in dietary fat content
      from approximately 20 to 40 E% during the first half of the century and a
      decrease to 30-34 E% during the last 20 years. Todays average diet contains
      satisfactory amounts of most nutrients. However, vitamin D levels are somewhat
      low, and among women of fertile age iron and folate intake is lower than
      recommended. Moreover, fat, sugar, salt, and alcohol content is higher than
      desirable, whereas fibrecontent is too low.

PMID- 9772821
TI  - [Measures to promote healthy dietary habits among schoolchildren].
AB  - The Norwegian National Nutrition Council has, over the past years, implemented a
      number of measures designed specifically to promote well-organized school meals
      and increase the consumption of fruit and vegetables among school children. These
      measures include the development of national guidelines for organizing school
      meals, economic support for trying out new methods of operating a school
      cafeteria, national campaigns to promote the traditional Norwegian packed lunch,
      open community meetings with political and administrative leaders at municipality
      level, the introduction of a system whereby pupils can purchase fresh fruit and
      vegetables at school, and advocacy through mass media. Results of an ongoing
      evaluation seem to indicate that these measures have had a positive effect on the
      organization of school meals. More young children are attended to by an adult
      during mealtimes, more pupils are allowed at least 20 minutes for their lunch
      break, and a growing number of secondary schools are introducing school
      cafeterias. However, only half of the total number of schools seem to be aware of
      the new guidelines, and much more work is required in order to ensure all
      students are provided with a well-organized school meal. Health personnel play a
      critical role in ensuring that this work is given political priority, also at the
      local level.

PMID- 9772822
TI  - [The extended concept of health--confusing as a concept and unmanageable in
      practice].

PMID- 9772823
TI  - [Disease and sick leave, the same thing?].

PMID- 9772824
TI  - [Leadership of hospital departments and professional conflicts. Quality strategy
      is the solution!].

PMID- 9772825
TI  - Reading in two alphabets.
AB  - Many speakers of Serbo-Croatian read the language in two phonemically precise and
      partially overlapping alphabets. Twenty years of experiments directed toward this
      ability have led to deeper understandings of the role of speech-related processes
      in reading and the contrasts and similarities among the world's alphabetic
      writing systems.

PMID- 9772827
TI  - The psychosocial effects of landmines in Cambodia.
AB  - The widespread use of landmines in conflict situations around the world and their
      continuing legacy for the civilian population in injuries, amputations,
      disabilities and economic costs has been recognized as a major problem. However,
      the psychosocial consequences for landmine victims are still to be realized.
      Although there are some facilities for the medical, orthopaedic and long-term
      rehabilitative care of landmine victims, hardly any exist for their psychosocial
      needs. This study considers the mental costs in terms of post-traumatic stress
      disorder, depression and anxiety. Individual difficulty in relationships and
      daily functioning is considerable, and the landmine victim faces social
      stigmatization, rejection and unemployment. Suggestions are made for brief
      training in relatively simple mental health care for staff working in already
      functioning programmes.

PMID- 9772826
TI  - The plutonium problem: the Royal Society sits on the fence.
AB  - A recent Royal Society report, Management of Separated Plutonium, considers the
      production and disposal of plutonium from the spent fuel from civil and nuclear
      power reactors. It accepts the need for dealing with plutonium stocks because of
      the toxicity of the element and as it can be used to fabricate nuclear weapons,
      and expresses concern that it might be illicitly acquired by terrorists. It
      recommends an independent Government commission on the management of plutonium,
      and considers the various options for this. However, it does not analyse the
      arguments against plutonium as a reactor fuel, and underestimates the risks of
      diversion to nuclear weapons and nuclear terrorism. This paper reviews the
      options, and concludes that separated plutonium should be added to high-level
      waste, vitrified, and eventually buried in a deep geological repository.

PMID- 9772828
TI  - The changing role of civilian surgeons in conflicts: a meta-analysis of
      epidemiological data.
AB  - Surgical activities in recent conflicts were reviewed based on the published
      epidemiological data. Ten articles on seven conflicts were identified and
      reviewed. The surgical activities in these articles were classified into three
      categories based on their activities: type 1, civilian border camp surgical
      activities; type 2, military hospitals in military deployment; type 3, civilian
      hospitals in former Yugoslavia or Palestine camp (most recent conflicts).
      Comparison of injuries in ratios of head-to-extremities, and critical part-to
      extremities, among these three different types of surgical activity showed that
      type 3 hospitals had a statistically higher number of critical part injuries
      compared to the other two types of hospital. Type 3 hospitals represent the most
      recent endemic, regional and indiscriminate killing experiences. The high rates
      of critical part trauma in studies of recent conflicts show the increasing
      importance of trauma management skills by civilian surgeons in recent conflicts.
      Exchange of information among civilian surgeons serving in these difficult and
      dangerous conditions should be encouraged.

PMID- 9772829
TI  - Herbal prostate remedies?

PMID- 9772831
TI  - When to start mammography.

PMID- 9772830
TI  - Caregivers' health is top priority, too.

PMID- 9772832
TI  - The language of war and breast cancer.

PMID- 9772834
TI  - Controlling PMS with calcium supplements.

PMID- 9772833
TI  - Cystitis in partners of Viagra users.

PMID- 9772835
TI  - Air cleaners and allergies.

PMID- 9772836
TI  - Whole grains for a healthy heart.

PMID- 9772837
TI  - DES daughters and cancer.

PMID- 9772838
TI  - Does hypochondria diminish with time?

PMID- 9772839
TI  - Earlier screening for Down's syndrome?

PMID- 9772840
TI  - New strategies for croup in children.

PMID- 9772841
TI  - A new twist in ecological studies.

PMID- 9772842
TI  - Consensus criteria for the classification of carpal tunnel syndrome in
      epidemiologic studies.
AB  - Criteria for the classification of carpal tunnel syndrome for use in
      epidemiologic studies were developed by means of a consensus process. Twelve
      medical researchers with experience in conducting epidemiologic studies of carpal
      tunnel syndrome participated in the process. The group reached agreement on
      several conceptual issues. First, there is no perfect gold standard for carpal
      tunnel syndrome. The combination of electrodiagnostic study findings and symptom
      characteristics will provide the most accurate information for classification of
      carpal tunnel syndrome. Second, use of only electrodiagnostic study findings is
      not recommended. Finally, in the absence of electrodiagnostic studies, specific
      combinations of symptom characteristics and physical examination findings may be
      useful in some settings but are likely to result in greater misclassification of
      disease status.

PMID- 9772843
TI  - Dementia is the major cause of functional dependence in the elderly: 3-year
      follow-up data from a population-based study.
AB  - OBJECTIVES: The purpose of this investigation was to study the role of dementia
      and other common age-related diseases as determinants of dependence in activities
      of daily living (ADL) in the elderly. METHODS: The study population consisted of
      1745 persons, aged 75 years and older, living in a district of Stockholm. They
      were examined at baseline and after a 3-year follow-up interval. Katz's index was
      used to measure functional status. Functional dependence at baseline, functional
      decline, and development of functional dependence at follow-up were examined in
      relation to sociodemographic characteristics and chronic conditions. RESULTS: At
      baseline, factors associated with functional dependence were age, dementia,
      cerebrovascular disease, heart disease, and hip fracture. However, only age and
      dementia were associated with the development of functional dependence and
      decline after 3 years. In a similar analysis, including only nondemented
      subjects. Mini-Mental State Examination scores emerged as one of the strongest
      determinants. The population attributable risk percentage of dementia in the
      development of functional dependence was 49%. CONCLUSIONS: In a very old
      population, dementia and cognitive impairment make the strongest contribution to
      both the development of long-term functional dependence and decline in function.

PMID- 9772844
TI  - Understanding trends in functional limitations among older Americans.
AB  - OBJECTIVES: This report documents trends in functional limitations among older
      Americans from 1984 to 1993 and investigates reasons for such trends. METHODS: We
      applied logistic regression to data for noninstitutionalized Americans aged 50
      years and older from the Survey of Income and Program Participation. We focused
      on 4 functional limitation measures unlikely to be affected by changes in role
      expectations and living environments: reported difficulty seeing words in a
      newspaper, lifting and carrying 10 pounds, climbing a flight of stairs, and
      walking a quarter of a mile. RESULTS: We found large declines in the crude
      prevalence of functional limitations, especially for those 80 years and older.
      Generally, changes in population composition explained only a small portion of
      the downward trends. Once changes in population composition and mobility-related
      device use were considered for difficulty walking, significant improvements in
      functioning remained for the 65- to 79-year-old group. CONCLUSIONS: Changes in
      population composition, device use, survey design, role expectations, and living
      environments do not appear to account completely for improvements in functioning.
      We infer that changes in under-lying physiological capability--whether real or
      perceived--likely underlie such trends.

PMID- 9772845
TI  - Predictors of healthy aging in men with high life expectancies.
AB  - OBJECTIVE: The purpose of this study was to identify risk factors that
      consistently predict staying healthy in contrast to developing clinical illness
      and/or physical and mental impairments. METHODS: More than 8000 men of Japanese
      ancestry were followed for 28 years with repeat examinations and surveillance for
      deaths and incident clinical illness. Physical and cognitive functions were
      measured in 1993. Measures of healthy aging included surviving and remaining free
      of major chronic illnesses and physical and cognitive impairments. RESULTS: Of
      6505 healthy men at baseline, 2524 (39%) died prior to the final exam. Of the
      3263 available survivors, 41% remained free of major clinical illnesses, 40%
      remained free of both physical and cognitive impairment, and 19% remained free of
      both illness and impairment. The most consistent predictors of healthy aging were
      low blood pressure, low serum glucose, not smoking cigarettes, and not being
      obese. CONCLUSIONS: Beyond the biological effects of aging, much of the illness
      and disability in the elderly is related to risk factors present at midlife.

PMID- 9772846
TI  - Religion and mortality among the community-dwelling elderly.
AB  - OBJECTIVES: This study analyzed the prospective association between attending
      religious services and all-cause mortality to determine whether the association
      is explainable by 6 confounding factors: demographics, health status, physical
      functioning, health habits, social functioning and support, and psychological
      state. METHODS: The association between self-reported religious attendance and
      subsequent mortality over 5 years for 1931 older residents of Marin County,
      California, was examined by proportional hazards regression. Interaction terms of
      religion with social support were used to explore whether other forms of social
      support could substitute for religion and diminish its protective effect.
      RESULTS: Persons who attended religious services had lower mortality than those
      who did not (age- and sex-adjusted relative hazard [RH] = 0.64; 95% confidence
      interval [CI] = 0.52, 0.78). Multivariate adjustment reduced this relationship
      only slightly (RH = 0.76; 95% CI = 0.62, 0.94), primarily by including physical
      functioning and social support. Contrary to hypothesis, religious attendance
      tended to be slightly more protective for those with high social support.
      CONCLUSIONS: Lower mortality rates for those who attend religious services are
      only partly explained by the 6 possible confounders listed above. Psychodynamic
      and other explanations need further investigation.

PMID- 9772847
TI  - Race and sex differences in long-term survival rates for elderly patients with
      pulmonary embolism.
AB  - OBJECTIVES: The goal of this study was to provide estimates of race- and sex
      specific survival rates over a 10-year period for a cohort of 49,752 Medicare
      patients admitted to the hospital in 1984 with a diagnosis of pulmonary embolism.
      METHODS: Data were derived from Medicare Provider Analysis and Review Record
      inpatient claims files and the National Death Index file. RESULTS: For a primary
      diagnosis of pulmonary embolism, median survival times among Black men and women
      were 2.5 years and 5.2 years, respectively; for White men and women, the median
      survival times were 4.3 years and 5.9 years, respectively. Median survival times
      for Black men and women and White men and women with a secondary diagnosis of
      pulmonary embolism were 0.4 years, 0.7 years, 0.8 years, and 1.4 years,
      respectively. Survival rates declined with advancing age. CONCLUSIONS: Overall,
      survival rates among Blacks were lower than those among Whites, and men had lower
      survival rates than women. These survival estimates provide new insights into
      outcomes following pulmonary embolism in hospitalized elderly people.

PMID- 9772848
TI  - Ex-smokers and risk of hip fracture.
AB  - OBJECTIVES: The purpose of this study was to examine the reversibility of the
      effect of smoking on hip fracture incidence rates. METHODS: A 3-year follow-up
      cohort study was conducted involving 35,767 adults 50 years of age or older. Of
      these individuals, 421 suffered a hip fracture. RESULTS: Among participants less
      than 75 years of age, the relative risk (RR) of hip fracture was elevated for ex
      smokers, even for those who had quit smoking more than 5 years previously (men:
      RR = 4.4, 95% confidence interval [CI] = 1.2, 15.3; women: RR = 1.3, 95% CI =
      0.6, 3.0), but was not as high as that for current smokers (men: RR = 5.0, 95% CI
      = 1.5, 16.9; women: RR = 1.9, 95% CI = 1.2, 3.1). CONCLUSIONS: The effect of
      smoking on risk of hip fracture was not reversed completely 5 years after smoking
      cessation.

PMID- 9772850
TI  - Targeting early antecedents to prevent tobacco smoking: findings from an
      epidemiologically based randomized field trial.
AB  - OBJECTIVES: This study examined whether interventions aimed at
      aggressive/disruptive classroom behavior and poor academic achievement would
      reduce the incidence of initiation of smoking. METHODS: An epidemiologically
      based, universal randomized preventive trial involved 2311 children in 2
      classroom-based preventive interventions or controls. Each intervention was
      directed at 1 of the aforementioned 2 antecedents over first and second grades in
      19 urban schools. RESULTS: Smoking initiation was reduced in both cohorts for
      boys assigned to the behavioral intervention. CONCLUSIONS: Targeting early risk
      antecedents such as aggressive behavior appears to be an important smoking
      prevention strategy.

PMID- 9772849
TI  - Targeting the underserved for breast and cervical cancer screening: the utility
      of ecological analysis using the National Health Interview Survey.
AB  - OBJECTIVES: This study tested the utility of ecological variables created from
      the National Health Interview Survey (NHIS) for strategic targeting of health
      services for the underserved. METHODS: Ecological variables were created using
      the 1989-1991 survey years of the NHIS public use data files. Segments, the NHIS
      secondary sampling units, permit computation of secondary sampling
      characteristics by percentage Black, percentage Hispanic, percentage below
      poverty, percentage unemployed, median education, median income, median age, and
      percentage residing in the United States for 5 years or less. These variables
      were analyzed with the NHIS Health Promotion and Disease Prevention 1990
      supplement reporting mammogram, clinical breast examination, and Pap test use.
      RESULTS: Median education of areas was inversely related to never having
      mammograms. Areas with a high proportion (70%-100%) of Hispanic respondents also
      were more likely not to have mammograms. Women residing in areas with moderate or
      high proportions of Hispanic respondents were more likely never to have clinical
      breast examinations and Pap tests, as were those in areas with low income,
      poverty, and respondents who had resided in the United States 5 years or less.
      CONCLUSIONS: The new methodology of constructing ecological variables using the
      NHIS demonstrates an application that may help identify underserved areas or
      areas with underutilized services. More studies using this methodology are
      warranted.

PMID- 9772851
TI  - The evolving epidemiology of chlamydial and gonococcal infections in response to
      control programs in Winnipeg, Canada.
AB  - OBJECTIVES: The purpose of this study was to describe and compare the
      transmission dynamics of chlamydia and gonorrhea in Winnipeg, Manitoba, Canada,
      and to assess implications for control programs. METHODS: Chlamydia and gonorrhea
      surveillance case reports (1988 through 1995) and contact-tracing reports (1991
      through 1995) were examined. RESULTS: High incidence rates of both chlamydia and
      gonorrhea clustered in geographic core areas characterized by low socioeconomic
      status. A decline in the number of reported cases of chlamydia (61%) and
      gonorrhea (64%) occurred between 1988 and 1995. For chlamydia, the decline was
      most prominent in non-core area cases, while for gonorrhea it was similar in core
      and non-core areas. CONCLUSIONS: Chlamydia and gonorrhea appear to be evolving
      through different epidemic phases, with chlamydia transmission, in response to a
      newly introduced control program, becoming more core dependent and gonorrhea
      transmission becoming more sporadic in the face of a sustained control effort.
      Focused control programs, based on an understanding of the transmission dynamics
      of chlamydia and gonorrhea, may make their elimination a feasible goal.

PMID- 9772852
TI  - Misclassification rates for current smokers misclassified as nonsmokers.
AB  - OBJECTIVES: This paper provides misclassification rates for current cigarette
      smokers who report themselves as nonsmokers. Such rates are important in
      determining smoker misclassification bias in the estimation of relative risks in
      passive smoking studies. METHODS: True smoking status, either occasional or
      regular, was determined for individual current smokers in 3 existing studies of
      nonsmokers by inspecting the cotinine levels of body fluids. The new data,
      combined with an approximately equal amount in the 1992 Environmental Protection
      Agency (EPA) report on passive smoking and lung cancer, yielded misclassification
      rates that not only had lower standard errors but also were stratified by sex and
      US minority majority status. RESULTS: The misclassification rates for the
      important category of female smokers misclassified as never smokers were,
      respectively, 0.8%, 6.0%, 2.8%, and 15.3% for majority regular, majority
      occasional, US minority regular, and US minority occasional smokers.
      Misclassification rates for males were mostly somewhat higher. CONCLUSIONS: The
      new information supports EPA's conclusion that smoker misclassification bias is
      small. Also, investigators are advised to pay attention to minority/majority
      status of cohorts when correcting for smoker misclassification bias.

PMID- 9772853
TI  - News media coverage and the epidemiology of homicide.
AB  - OBJECTIVES: This study assessed how newspaper coverage of homicides corresponds
      to the epidemiology of homicide. METHODS: Stories in the Los Angeles Times about
      homicide (n = 2782) were compared with the homicides that occurred in Los Angeles
      County from 1990 through 1994 (n = 9442). The generalized linear model assessed
      how victim, incident, and suspect characteristics related to coverage. RESULTS:
      Even when multiple variables were taken into account, some homicides (those with
      female, child, or elderly victims; those in which the suspect was a stranger to
      the victim; those in wealthier neighborhoods) received more coverage and others
      (those with Black or Hispanic victims or victims with less than a high school
      education; those committed with nonfirearm weapons; those in which the suspect
      was an intimate of the victim) received less coverage than expected. CONCLUSIONS:
      Some homicides are more newsworthy than others. Potential implications of not
      providing the public with representative data are discussed.

PMID- 9772854
TI  - Prevalence of adult domestic violence among women seeking routine care in a
      Native American health care facility.
AB  - OBJECTIVES: The purpose of this study was to determine the prevalence of, and
      sociodemographic factors associated with, adult domestic violence within a Native
      American community. METHODS: Adult women in the community were surveyed. RESULTS:
      Of 371 eligible women, 341 (92%) were surveyed. Among respondents, 179 reported a
      history of at least 1 episode of domestic violence. Fifty-six (16.4%) reported
      violence within the previous 12 months. Age under 40 years and living in a
      household receiving governmental financial assistance were independently
      associated with 1-year prevalence of adult domestic violence. CONCLUSIONS: Adult
      domestic violence is prevalent within this Native American community. Additional
      research is required to characterize further the relationship between domestic
      violence and socioeconomic status.

PMID- 9772855
TI  - Depression, anxiety, and smoking initiation: a prospective study over 3 years.
AB  - OBJECTIVES: This report considers the extent to which depression and anxiety
      predict smoking onset in adolescence. METHODS: A 6-wave cohort design was used to
      study a sample of 14- and 15-year-old students (n = 2032) drawn from 44 secondary
      schools in the state of Victoria, Australia. The students were surveyed between
      1992 and 1995 with a computerized questionnaire that included a 7-day
      retrospective diary for tobacco use and a structured psychiatric interview.
      RESULTS: Experimental smokers were 29 times more likely than non-smokers to make
      a transition into daily use in the subsequent 6 months. Depression and anxiety,
      along with peer smoking, predicted initiation of experimental smoking.
      Specifically, depression and anxiety accentuated risks associated with peer
      smoking and predicted experimentation only in the presence of peer smoking.
      CONCLUSIONS: The finding that experimental smoking is an overwhelmingly strong
      predictor of later daily smoking focuses attention on smoking initiation.
      Depressive and anxiety symptoms are associated with higher risks for initiation
      through an increased susceptibility to peer smoking influences. Promoting the
      psychological well-being of adolescents and addressing perceived interpersonal
      benefits of smoking may play a role in the prevention of adolescent tobacco use.

PMID- 9772856
TI  - Does passive smoking in early pregnancy increase the risk of small-for
      gestational-age infants?
AB  - OBJECTIVES: This study tested the hypothesis that women who deliver small-for
      gestational-age infants are more often exposed to passive smoking at home or at
      work. METHODS: Among a 1-year cohort of nulliparous women in the city of Malmo,
      Sweden 872 (87.7%) women completed a questionnaire during their first prenatal
      visit. The study was carried out among women whose pregnancies resulted in a
      singleton live birth (n = 826), 6.7% of infants were classified as small for
      their gestational age. RESULTS: Passive smoking in early pregnancy was shown to
      double a woman's risk of delivering a small-for-gestational-age infant,
      independent of potential confounding factors such as age, height, weight,
      nationality, educational level, and the mother's own active smoking (odds ratio
      [OR] = 2.7). A stratified analysis indicated interactional effects of maternal
      smoking and passive smoking on relative small-for-gestational-age risk.
      CONCLUSIONS: Based on an attributable risk estimate, a considerable reduction in
      the incidence of small-for-gestational-age births could be reached if pregnant
      women were not exposed to passive smoking.

PMID- 9772857
TI  - Maternal leisure-time exercise and timely delivery.
AB  - OBJECTIVES: This study investigated whether, in a general obstetric population,
      exercise in pregnancy affects the timeliness of delivery. The hypothesis was that
      maternal exercise would not raise the risk of preterm birth. METHODS: A community
      cohort of 557 prenatal patients was followed up until the time of delivery. Data
      were collected on exercise in each trimester: none, low-moderate (< 1000 kcal
      [4184 kJ]/wk in energy expenditure), or heavy (> or = 1000 kcal/wk). Timely
      delivery was adopted as an outcome criterion. Thus, in the analysis, a term birth
      was treated as optimal and survival techniques were used to estimate risks for
      both preterm and postdates delivery. RESULTS: No association was found between
      low-moderate exercise and gestational length. Heavier exercise appeared to
      reduce, rather than raise, the risk of preterm birth. The adjusted relative risk
      among conditioned heavy exercisers was 0.11 (95% confidence interval = 0.02,
      0.81). After term, conditioned heavy exercisers delivered faster than
      nonexercisers. CONCLUSIONS: The most important finding was the lack of evidence
      that vigorous maternal exercise is a risk factor for preterm delivery. A
      promising finding was that conditioned heavy exercisers have timely deliveries.

PMID- 9772858
TI  - Maternal anthropometric factors and risk of primary cesarean delivery.
AB  - OBJECTIVES: This study examined absolute and proportional gestational weight gain
      and prepregnancy body mass index as predictors of primary cesarean delivery.
      METHODS: Data were derived from a prospective study of pregnancy outcome risk
      factors in 2301 women in greater New Haven, Conn, who had singleton deliveries by
      primary cesarean (n = 312) or vaginal delivery (n = 1989) and for whom height,
      prepregnancy weight, and weight gain were available. Women were divided into 4
      body mass index groups (underweight, low average, high average, and obese) and
      further subdivided into 8 groups according to median proportional or absolute
      weight gain. RESULTS: Risk of cesarean delivery increased with increasing body
      mass index and gestational weight gain greater than the median for one's body
      mass index. Proportional weight gain was more predictive of cesarean delivery
      than absolute weight gain. Underweight women gaining more than 27.8% of their
      prepregnancy weight had a 2-fold adjusted relative risk of cesarean delivery.
      CONCLUSIONS: Proportional weight gain is an important predictor of cesarean
      delivery for underweight women; high body mass index is also predictive of
      increased risk.

PMID- 9772859
TI  - The importance of continuity of care in the likelihood of future hospitalization:
      is site of care equivalent to a primary clinician?
AB  - OBJECTIVES: This study examined the effect of continuity with clinicians and
      health care sites on likelihood of future hospitalization. METHODS: Delaware
      Medicaid patient data were analyzed. Logistic regression models supplied adjusted
      effects of continuity on hospitalization. RESULTS: Patients in the high clinician
      continuity group had lower odds of hospitalization than patients in the high
      site/low clinician continuity group (odds ratio [OR] = 0.75, 95% confidence
      interval [CI] = 0.66, 0.87). The latter group did not differ from the low
      site/low clinician continuity group (OR = 0.93, 95% CI = 0.80, 1.08).
      CONCLUSIONS: A location providing health care without clinician continuity may
      not be sufficient to ensure cost-effective care.

PMID- 9772860
TI  - Patterns of condom use among adolescents: the impact of mother-adolescent
      communication.
AB  - OBJECTIVES: The association between the timing of discussions about condoms
      between mother and adolescent and adolescents' condom use during their first and
      subsequent sexual encounters was examined. METHODS: Sexually active adolescents
      reported whether and when they discussed condoms with their mother and answered
      questions about their own condom use. RESULTS: Mother-adolescent discussions
      about condoms that occurred prior to sexual debut were strongly associated with
      greater condom use during first intercourse and most recent intercourse, along
      with greater lifetime regular condom use. CONCLUSIONS: Discussions about condoms
      prior to sexual debut are important in promoting condom use among adolescents.

PMID- 9772861
TI  - A rivalry of foulness: official and unofficial investigations of the London
      cholera epidemic of 1854.
AB  - Contemporaneous with John Snow's famous study of the 1854 London cholera epidemic
      were 2 other investigations: a local study of the Broad Street outbreak and an
      investigation of the entire epidemic, undertaken by England's General Board of
      Health. More than a quarter-century prior to Koch's description of Vibrio comma,
      a Board of Health investigator saw microscopic "vibriones" in the rice-water
      stools of cholera patients that, in his later life, he concluded had been cholera
      bacilli. Although this finding was potential evidence for Snow's view that
      cholera was due to a contagious and probably live agent transmitted in the water
      supply, the Board of Health rejected Snow's conclusions. The Board of Health
      amassed a huge amount of information which it interpreted as supportive of its
      conclusion that the epidemic was attributable not so much to water as to air.
      Snow, by contrast, systematically tested his hypothesis that cholera was water
      borne by exploring evidence that at first glance ran contrary to his
      expectations. Snow's success provides support for using a hypothetico-deductive
      approach in epidemiology, based on tightly focused hypotheses strongly grounded
      in pathophysiology.

PMID- 9772862
TI  - Maternal smoking and deformities of the foot: results of the EUROCAT Study.
      European Registries of Congenital Anomalies.

PMID- 9772863
TI  - Issues in comparing survival rates for Detroit and Toronto.

PMID- 9772864
TI  - First aid training: the hidden dimension of injury control for school-based
      injuries.

PMID- 9772865
TI  - Nephron-sparing surgery for renal cell carcinoma.
AB  - In summary, NSS is the indicated treatment for patients with localized RCC and an
      intercurrent urological or medical condition that poses a threat to overall renal
      function. Recent studies have clarified the role of NSS in patients with
      localized unilateral RCC and a normal contralateral kidney. Recent results
      indicate that radical nephrectomy and NSS provide equally effective curative
      treatment for patients who present with a single, small (< 4 cm), and clearly
      localized RCC. The long-term renal functional advantage of NSS with a normal
      opposite kidney requires further study.

PMID- 9772866
TI  - Medical photography and genitourinary surgery.

PMID- 9772867
TI  - Disorders of ejaculation: congenital, acquired and functional.

PMID- 9772868
TI  - Holmium: YAG lasertripsy for ureteric calculi: an experience of 300 procedures.
AB  - OBJECTIVE: To assess the success of holmium:YAG lasertripsy in the management of
      ureteric calculi and to audit the complications of the procedure, with special
      reference to strictures in the ureter. PATIENTS AND METHODS: A total of 300
      ureteroscopic laser procedures were carried out on 265 patients (204 male and 61
      female, median age 51 years, range 2-95) with ureteric calculi. At ureteroscopy,
      the calculi were present in the upper ureter in 44%, mid-ureter in 37% and lower
      ureter in 19% of patients; most calculi were > 5 mm. A 7.5 F Wolf semi-rigid
      ureteroscope was used and the holmium:YAG laser energy delivered using the
      Sharplan ML210 device at 0.8-1.0 J/pulse. The patients were followed up at
      approximately 6 weeks with limited intravenous urography or ultrasonography to
      assess clearance and the incidence of strictures. RESULTS: Stones were completely
      cleared in 90% of the patients, with the best results in the lower and mid-ureter
      (97% and 96%, respectively) followed by the upper ureter (89%). Alternative
      procedures were required in only 17 (7%) patients; extracorporeal shock-wave
      lithotripsy in 13, percutaneous nephrolithotomy in two and open pyelolithotomy in
      two patients. Complications with ureteric perforation in 11 patients, including
      laparotomy for peritonitis in one, serious sepsis in two and strictures in 10
      patients. Strictures were more common in association with impacted calculi in the
      upper ureter early in the series. CONCLUSIONS: Holmium:YAG lasertripsy is a
      highly effective treatment for ureteric calculi, with strictures related to the
      treatment of difficult upper ureteric calculi.

PMID- 9772869
TI  - Can preoperative psychological defensive strategies, mood and type of lower
      urinary tract reconstruction predict psychosocial adjustment after cystectomy in
      patients with bladder cancer?
AB  - OBJECTIVES: To assess if there is relationship between: (i) preoperative
      psychological defensive strategies, mood and type of lower urinary tract
      reconstruction, and (ii) psychosocial adaptation after radical cystectomy for
      bladder cancer. PATIENTS AND METHODS: Fifty-seven consecutive patients (44 men
      and 13 women, mean age 62 years, range 34-81) undergoing radical cystectomy
      (ileal conduit urinary diversion in 17, continent cutaneous diversion in 22 and
      orthotopic bladder replacement in 18) were assessed preoperatively using the meta
      contrast technique (MCT), a projective test to reveal individual defensive
      strategies. From the results the patients were classified as hypothetical 'at
      risk' or 'no risk' patients for postoperative psychosocial complications. An 'at
      risk' patient was designated as one who showed neurotic defensive strategies in
      coping with threats, i.e. primitive, immature or regressive strategies or even
      lack of defence in connection with pronounced anxiety. All patients completed a
      questionnaire and were interviewed; 10 questions dealt with mood, five reflecting
      anxiety and five the depressive states. The questionnaire and the interview were
      repeated 3 and 12 months, and 5 years after surgery. RESULTS: The remembered
      difficulties during the first month after discharge from hospital differed
      between the 'risk' and 'no risk' groups after 1 and 5 years. On a visual analogue
      scale (VAS) the 'risk' patients had very low scores (less difficulty) or very
      high, while the 'no risk' patients had intermediate scores. VAS score were also
      higher, although not significantly so, in patients using primitive defence
      strategies. The psychosocial situation did not differ between the groups in the
      first year, but at 5 years there were differences in self-esteem and
      interpersonal contact-seeking. High depression scores before surgery were
      associated with high VAS scores at 3 months when recalling the first month after
      discharge, but the anxiety score was not predictive. Men with orthotopic bladder
      replacement adapted less well throughout the 5 year follow-up. Elderly patients
      with stereotypy (the commonest defensive strategy at these ages) adapted
      relatively well to ileal conduit diversion. About 20% of patients had difficulty
      in accepting the postoperative situation, regardless of urinary diversion modes.
      CONCLUSION: The combination of defensive strategies assessed using the MCT and
      selected on hypothetical grounds was less discriminatory than expected for those
      at risk of postoperative psychosocial problems. However, those with primitive
      strategies apparently had a long-term risk of poor adaptation. The search for an
      optimal instrument for the identification of patients at risk is warranted. In
      this study, patients with a 'wet' stoma did not seem to fare less well than those
      with a continent reconstruction.

PMID- 9772870
TI  - Bladder preservation in muscle-invasive bladder cancer.

PMID- 9772871
TI  - 'Nerve-sparing' cystectomy and substitution cystoplasty in patients of either
      sex: limitations and techniques.
AB  - OBJECTIVES: To determine the limitations of cystectomy and orthotopic
      substitution cystoplasty in men and women with bladder cancer. PATIENTS AND
      METHODS: Cystectomy and orthotopic substitution cystoplasty were carried out in
      79 patients (mean age 60 years, range 31-74, including eight women) who were
      followed for a mean of 7 years (range 1-13) to evaluate continence, potency and
      survival. RESULTS: Overall, 80% of the patients were continent without further
      treatment and 55% of the men who were potent before surgery remained so
      afterward. The best results were obtained with retrograde cystectomy in both
      sexes and are only achievable in women in this way. Continence was achieved more
      easily in women than in men, although pathological delineation of the tumour
      preoperatively and technical considerations per-operatively make both the
      selection and the procedure more demanding in women than in men. CONCLUSIONS:
      Cystectomy and orthotopic substitution cystoplasty is possible in patients of
      either sex and should be offered to all patients as an alternative to ileal
      conduit urinary diversion, unless preoperative assessment suggests that the
      urethra must be removed with the bladder, which is rare in men and uncommon in
      women. In such patients, a continent diversion may be the preferred option.

PMID- 9772872
TI  - Adjuvant chemotherapy for high-risk urothelial transitional cell carcinoma: the
      Princess Margaret Hospital experience.
AB  - OBJECTIVE: To review the outcome of adjuvant systemic chemotherapy after surgery
      for patients with locally advanced urothelial transitional cell carcinoma (TCC)
      of the bladder and upper urinary tract who were at high risk for recurrence or
      metastatic spread. PATIENTS AND METHODS: Thirty-five patients (27 men and eight
      women, median age 59 years) received adjuvant chemotherapy and were followed for
      a median of 31 months from surgery (range 12-109). All patients had undergone
      surgery (cystectomy, nephrectomy, nephrouretectomy), with removal of all evident
      tumour from the following primary sites: bladder (29), renal pelvis (three) and
      ureter (three). Thirty patients had stage pT3 or greater, 22 had node-positive
      disease and 16 had vascular invasion. The median interval from surgery to
      chemotherapy was 2 months. Patients received a median of four courses of
      cisplatin, methotrexate and vinblastine (n = 23) or the same drugs with
      doxorubicin (n = 12). RESULTS: Toxicity included nine episodes of febrile
      neutropenia (one fatal) and six episodes of thromboembolism (one fatal). Eighteen
      patients (51%) remain alive and free of apparent disease with a median follow-up
      of 31 months. Actuarial overall and relapse-free survival were 64% and 57% at 2
      years and 47% and 53% at 5 years, respectively. For the 22 node-positive
      patients, the median relapse-free survival and overall survival was 22 months and
      33 months, respectively. CONCLUSIONS: Patients with urothelial TCC at high risk
      of relapse after radical surgery can have a reasonable chance of long-term
      survival with systemic adjuvant chemotherapy. Treatment is associated with
      toxicity. The benefits of treatment should be addressed in a large randomized
      controlled trial.

PMID- 9772873
TI  - Terazosin in benign prostatic hyperplasia: effects on blood pressure in
      normotensive and hypertensive men.
AB  - OBJECTIVE: To determine the effects of terazosin on blood pressure and on
      antihypertensive therapy when used in managing benign prostatic hyperplasia
      (BPH). PATIENTS AND METHODS: Safety data from a large, multinational study were
      analysed retrospectively. Normotensive and hypertensive patients received
      escalating dosages of terazosin for 10 weeks and were maintained on 5 or 10 mg
      daily doses for 16 weeks (single-blind period). After the initial treatment
      period, only men having sufficient improvements in International Prostate Symptom
      Score (> or = 30%) and in peak flow rate (> or = 10%) were randomly assigned to
      continue terazosin or to receive placebo for 24 weeks (double-blind period).
      RESULTS: In hypertensive patients, terazosin reduced systolic blood pressure
      (SBP) and diastolic blood pressure (DBP) during the single-blind period; these
      clinically significant reductions were maintained in patients receiving terazosin
      during the double-blind period. However, in normotensive and controlled
      hypertensive patients terazosin produced no clinically significant mean changes
      in SBP or DBP during either study period. Terazosin did not adversely affect
      patients receiving concomitant antihypertensive medication. CONCLUSION: Terazosin
      is a safe treatment for BPH in normotensive and hypertensive men, including men
      who are already taking additional antihypertensive drugs.

PMID- 9772874
TI  - Zonal variation of apoptosis and proliferation in the normal prostate and in
      benign prostatic hyperplasia.
AB  - OBJECTIVE: To determine whether benign prostatic hyperplasia (BPH) results from
      an imbalance between cell proliferation and apoptosis, and the extent to which
      the rates of these opposing processes are altered with the expression of the anti
      death oncoprotein bcl-2. MATERIALS AND METHODS: Ten prostate glands from normal
      men (mean age 43.7 years) were sampled according to McNeal's zonal anatomy, in
      addition to 30 prostate adenomas obtained from prostatectomy specimens from
      symptomatic patients (mean age 61.4 years). Tissue samples were fixed in formalin
      and embedded in paraffin. Proliferation and bcl-2 expression were assessed by
      immunostaining using Mib-1 and anti-bcl-2 antibodies, while apoptotic bodies were
      specifically stained using in situ nick translation. The percentage of positive
      cells was determined by optical microscopy. RESULTS: In normal epithelium, the
      rates of proliferation and apoptosis were increased in the peripheral zone (Mib-1
      1.7%, apoptotic bodies 3.3%) compared with the central (0.2% vs 1.4%) and
      transition (0.1% vs 1.8%) zones. Proliferation was significantly greater in BPH
      than in normal prostate tissue (3.7%), contrasting with a stable rate of
      apoptosis (1.4%). In the normal prostate, bcl-2 was expressed by glandular and
      basal cells in the peripheral zone. In the central zone, bcl-2 was overexpressed
      in basal cells and in most glandular cells of the intraluminal ridges. Bcl-2
      expression in the transition zone was limited to dispersed basal cells. In BPH,
      bcl-2 was strongly expressed by basal cells in mature glandular formations and in
      most cells of young small nodules. CONCLUSION: BPH may result from both an
      increase of proliferation within the basal compartment and a failure of apoptosis
      to counterbalance basal cell proliferation. Increased expression of bcl-2 may
      participate in this process by blocking apoptosis.

PMID- 9772875
TI  - The role of power Doppler ultrasonography in the diagnosis of prostate cancer: a
      preliminary study.
AB  - OBJECTIVE: To determine the role of transrectal power Doppler ultrasonography
      (PDU) in the diagnosis of prostate cancer. PATIENTS AND METHODS: Thirty-six
      patients (mean age 66.4 years, SD 7.7, range 59-82) with possible prostate
      cancer, suspected from an abnormal digital rectal examination or elevated
      prostate specific antigen level, underwent transrectal ultrasonography,
      transrectal PDU and biopsy. The vascularity on PDU was graded on a scale of 0-2,
      where grade 1-2 was considered positive and grade 0 negative. RESULTS: The
      vascularity was grade 2 in 11 patients, grade 1 in 11 and grade 0 in 14; 20 of
      the 36 (56%) patients had prostate cancer. Of the 22 patients positive on PDU, 18
      had malignant disease and four benign; two of 20 patients with
      histopathologically confirmed malignancy had a normal PDU. The sensitivity of PDU
      was 90%, the specificity 75% and the positive predictive value 82%. CONCLUSION:
      Focal hypervascularity on PDU was associated with an increased likelihood of
      prostate cancer. Although ultrasonography alone cannot detect all cancers, even
      using PDU, the technique appears to increase the sensitivity and to help identify
      appropriate sites for biopsy.

PMID- 9772876
TI  - Influence of free-to-total prostate specific antigen variability on the early
      diagnosis of prostate cancer: a comparative study of three immunoassays.
AB  - OBJECTIVE: To compare three immunoassays for total prostate specific antigen
      (tPSA), free PSA (fPSA), free-to-total PSA ratio (f/tPSA), and the f/tPSA
      thresholds for optimal differentiation between benign prostatic hypertrophy (BPH)
      and prostate cancer in 141 consecutive patients referred for prostatic disease.
      PATIENTS AND METHODS: The study included 43 patients with prostate cancer and 98
      with BPH, all confirmed histologically. PSA levels were assessed using the
      following assay kits just before histological analysis of the prostate; Hybritech
      (Tandem-R PSA, normal values, NV, < 4 ng/mL, and Tandem-R free PSA), Cis Bio (PSA
      RIACT, NV < 2.5 ng/mL and fPSA-RIACT) and Immunocorp (PSA-IRMA, NV < 4 ng/mL and
      Free PSA-IRMA). The results were assessed to determine the sensitivity,
      specificity and threshold values of the different assays to differentiate
      patients with BPH and cancer. RESULTS: The mean tPSA and f/tPSA ratio were
      statistically different in assays with different NVs. The mean fPSA values
      differed significantly between the Hybritech and Cis Bio, between the Hybritech
      and Immunocorp but not between the Cis Bio and Immunocorp assays. With receiver
      operator curve analysis, there were no statistically significant differences
      among the three immunoassays in f/tPSA (0.72 for Hybritech, 0.73 for Cis Bio and
      0.64 for Immunocorp) or between the tPSA and fPSA curves for each manufacturer.
      With the sensitivity fixed at 90%, different f/tPSA thresholds were defined
      (0.22, 0.34 and 0.25 for Hybritech, Cis Bio and Immunocorp, respectively). The
      specificities (i.e. the percentage of unnecessary biopsies spared) were 22%, 21%
      and 31%, respectively (not significantly different). CONCLUSION: Each immunoassay
      could be used to distinguish prostate cancer and BPH at different f/tPSA
      thresholds, with 21-30% of unnecessary biopsies spared. There was no difference
      in overall performance among the different assays. Further studies are needed to
      better define the exact use of the f/tPSA ratio in the routine diagnosis of
      prostate cancer.

PMID- 9772877
TI  - The value of prostate specific antigen (PSA) density and free: total PSA ratio in
      selecting patients with a normal digital rectal examination and intermediate
      total PSA levels for further investigation.
AB  - OBJECTIVES: To examine the use of prostate-specific antigen (PSA) density (PSAD)
      and free to total PSA ratio (f/tPSA) in enhancing the specificity of PSA in the
      diagnosis of prostate cancer in patients with a total PSA (tPSA) of 4-10 ng/mL
      and with a normal digital rectal examination (DRE). PATIENTS AND METHODS: The
      study comprised 77 consecutive men in whom the fPSA and tPSA levels were obtained
      before DRE and transrectal ultrasonography-guided sextant prostate biopsy.
      Prostate cancer was found in 39 patients and the histology was benign in 38.
      Receiver operator characteristic curves, obtained from all 77 patients, were used
      to determine the optimal thresholds for PSAD and f/tPSA in detecting cancer. A
      subset of 28 patients, including seven with prostate cancer, was identified who
      had a normal DRE and a tPSA of 4-10 ng/mL; PSAD and f/tPSA values were applied at
      the optimal thresholds to assess their use in identifying those patients with
      cancer. RESULTS: When applied to the selected group of 28 patients, the PSAD
      (threshold 0.15) failed to identify any with prostate cancer. The f/tPSA
      (threshold 0.12) yielded a sensitivity of 65% and a specificity of 38%,
      identifying only three of seven patients with cancer. By increasing the threshold
      to 0.25, six patients were correctly identified, giving a sensitivity of 86%,
      with a lower specificity of 14%. CONCLUSIONS: These findings suggest that the
      neither PSAD nor f/tPSA either significantly reduce the negative biopsy rate or
      identify patients at greater risk of prostate cancer, particularly when the tPSA
      is equivocal at 4-10 ng/mL.

PMID- 9772878
TI  - Prolonged increase in micturition threshold volume by anogenital afferent
      stimulation in the rat.
AB  - OBJECTIVE: To investigate whether anogenital afferent stimulation induces a
      prolonged increase in the micturition threshold volume of anaesthetized rats.
      MATERIALS AND METHODS: Thirteen female rats, anaesthetized by alpha-chloralose
      and paralysed by pancuronium bromide were used for the experiments. The
      micturition threshold volume was determined by repeated cystometry. In two
      experiments, afferent activity was recorded from the exposed pudendal nerve;
      vaginal and anal afferents were stimulated electrically by ring electrodes. In
      one experiment, the dorsal clitoris nerves were exposed bilaterally and mounted
      for electrical stimulation. The afferents were stimulated continuously for 5 min
      at 10 Hz, using unipolar cathodic pulses of 0.5 ms duration with an amplitude of
      10 mA (or 0.8 mA for the dorsal clitoral nerves). RESULTS: Anogenital stimulation
      for 5 min induced a significant and prolonged increase in the micturition
      threshold volume (from a median value of 0.35 mL before to 0.45 mL after
      stimulation; P < 0.01). The increase in threshold volume was maintained for about
      40 min after the end of stimulation. There was no obvious difference in effect
      between the stimulation sites nor with direct dorsal clitoral nerve stimulation.
      Neither the micturition threshold pressure nor the maximal contraction pressure
      were altered by stimulation. No tonic afferent after-discharge could be detected
      in the pudendal nerve recordings. CONCLUSIONS: Artificial electrical stimulation
      of anogenital afferents induced a prolonged increase in the micturition threshold
      volume of anaesthetized rats. The change presumably involved the modulation of
      the synaptic transmission in the central micturition reflex pathway. It is
      proposed that the observed change represents the first step in the curative 're
      education' process induced in patients with urge incontinence by electrical
      stimulation of anovaginal afferents.

PMID- 9772879
TI  - Fertility and histological studies in a unilateral cryptorchid rat model during
      early and late adulthood.
AB  - OBJECTIVE: To investigate the effect of age on fertility and testicular
      development in rats with untreated unilateral undescended testes. MATERIALS AND
      METHODS: Newborn male Wistar King-A rats were divided into two groups. In group
      1, a mechanical model of unilateral undescended testis was created by performing
      extra-abdominal fixation of the gubernaculum in the neonatal period, and in group
      2, sham-operated rats were used as controls. At 90 days old (early adulthood),
      the fertility of both groups was assessed by mating the rats with mature virgin
      females for 2 weeks. Thereafter, some of the rats were killed and their testes
      examined histologically, while the remaining rats were allowed to develop
      further. At the age of 180 days (late adulthood), fertility was re-assessed in
      the same way. All the rats were then killed and their testes removed for
      histological examination. RESULTS: There was no significant difference in
      pregnancy rate of females mated with males from either group in early adulthood.
      However, in late adulthood there was a significant reduction in pregnancy rate in
      females coupled with cryptorchid rats compared with that of females coupled with
      control rats. There was a significant degeneration of the unilateral cryptorchid
      testes compared with control testes in both early and late adulthood. In
      contrast, there were no significant changes in histological development between
      the contralateral scrotal testes and the controls in early adulthood, although
      they were significantly different from the controls in late adulthood.
      CONCLUSION: These results suggest that fertility is affected by ageing in
      untreated unilateral cryptorchidism; this may be induced by extensive damage not
      only in the undescended testes, but also in the contralateral scrotal testis, in
      this mechanically induced model of unilateral cryptorchidism.

PMID- 9772880
TI  - A histological study of Denonvilliers' fascia and its relationship to the
      neurovascular bundle.
AB  - OBJECTIVE: To evaluate the anatomical relationship between the nerves and fasciae
      at the site of dissection in a radical retropubic prostatectomy. MATERIALS AND
      METHODS: Eight adult male (autopsy) en bloc specimens of bladder and rectum were
      examined histologically after staining with either haematoxylin and eosin or S
      100 protein (as a specific nerve stain). RESULTS: All specimens showed
      Denovilliers' fascia to have no clearly defined layers and no definable lateral
      edge. No distinct neurovascular bundle was seen but nerves were scattered
      throughout the fasciae, including medially towards the midline. CONCLUSION: In
      radical retropubic prostatectomy, a piece of Denonvilliers' fascia is taken with
      the specimen, thus removing these nerves. The loss of these nerve fibres may
      explain the significant rate of erectile dysfunction after 'nerve-sparing'
      surgery.

PMID- 9772881
TI  - Composition and biomechanical properties of the bladder acellular matrix graft:
      comparative analysis in rat, pig and human.
AB  - OBJECTIVE: To compare the composition and mechanical properties of the newly
      developed bladder acellular matrix graft (BAMG) with the normal urinary bladder
      in rat, pig and human. MATERIALS AND METHODS: Rat, pig and human urinary bladders
      were harvested and divided into control and experimental groups. For the latter,
      BAMGs were prepared, and light and transmission electron microscopic studies
      performed. Strips from the normal bladders and the BAMGs (10 in each group) were
      tested under tension, and the ultimate tensile strength, maximum strain, and
      elastic modulus were determined from stress/strain curves. RESULTS: Both types I
      and III collagen, as well as elastic fibres, were observed as major components of
      the matrix scaffold. There were more collagen type I fibres in the rat than in
      the pig and human BAMGs, whereas the pig, and particularly the human, both showed
      higher levels of type III collagen and elastic fibres. These different matrix
      scaffold patterns were confirmed by electron microscopy. Results from
      biomechanical testing showed no significant differences for strength, strain or
      elastic modulus between BAMG and control bladder strips, except in the rat where
      the maximum strain values were significantly lower. CONCLUSION: There are
      variations in the acellular matrix structure with similar biomechanical
      properties between the BAMG and the normal urinary bladder in three different
      species. These results may underscore the potential of the BAMG. Furthermore,
      this in vitro model provides a suitable method to study the mechanical properties
      of the urinary bladder and may serve as a diagnostic tool for various
      investigations.

PMID- 9772882
TI  - A conscious-rabbit model for the long-term observation of urethral and arterial
      pressures.
AB  - OBJECTIVE: To describe and evaluate a new experimental model for the simultaneous
      measurement of urethral (UP) and arterial (AP) pressures in the conscious rabbit,
      thereby avoiding the interference of anaesthesia which markedly reduces reflex
      activity and tone of smooth muscle. MATERIALS AND METHODS: Female rabbits were
      anaesthetized and catheters inserted into the urethra, abdominal aorta, jugular
      vein and bladder. After recovering from surgery, rabbits were trained to remain
      static in a sling for a period of 2 h, during which the UP and AP were recorded.
      The model was validated for short- and long-term stability before the effects of
      drugs were assessed; UP and AP were recorded for up to 60 min after drug/solvent
      administration to assess short-term stability, and long-term stability was
      assessed by comparing 60 min control periods between the first and fifth
      experimental session up to a month apart. RESULTS: Over 60 min in the control
      group, the UP remained steady, whereas the AP only decreased slightly. Recordings
      were made during five subsequent control periods, with at least 3 days of rest
      between successive assessments, and the UP and AP remained similar for up to 1
      month. During a second phase, the effect of alpha 1-adrenoceptor agonists on both
      pressures were evaluated to characterize their functional uroselectivity. De
      glymidodrine and L-phenylephrine (0.1 mg/kg) were administered intravenously; the
      UP increased by 18 cmH2O (146%) and 21 cmH2O (173%), respectively, whereas AP
      increased by 22 mmHg (31%) and 47 mmHg (63%), respectively. At 5 min after
      administering the drugs, the UP remained higher by 16 cmH2O (121%) with de
      glymidodrine, whereas it had returned to basal values with L-phenylephrine.
      CONCLUSIONS: This conscious-animal model allows the simultaneous measurement of
      UP and AP in the absence of anaesthesia. It provides a useful means to directly
      evaluate the effects of a drug on the urogenital and cardiovascular systems, and
      thereby its functional uroselectivity.

PMID- 9772883
TI  - The monoclonal antibody 7E12H12 can differentiate primary adenocarcinoma of the
      bladder and prostate.
AB  - OBJECTIVE: To determine if the monoclonal antibody 7E12H12, which reacts with a
      40 kDa protein in normal human enterocytes and has been shown to be a marker for
      intestinal metaplasia and adenocarcinoma arising in the bladder, could assist in
      distinguishing prostatic, urachal and vesical adenocarcinoma, using a sensitive
      immunohistochemical assay. MATERIALS AND METHODS: Fifteen primary prostatic
      adenocarcinomas and five adenocarcinomas of the urinary bladder were selected for
      a retrospective evaluation. The monoclonal antibody 7E12H12 (IgM isotype) was
      used in an immunoperoxidase assay to survey formalin-fixed, paraffin-embedded
      archival tissue specimens. RESULTS: All vesical adenocarcinomas reacted
      positively with the antibody, regardless of grade; none of the 15 prostatic
      specimens reacted positively in either the benign or malignant glandular
      epithelium. CONCLUSION: The monoclonal antibody 7E12H12 can differentiate primary
      adenocarcinoma of the bladder from secondary adenocarcinoma arising in the
      prostate and may be a useful tool in diagnostic pathology.

PMID- 9772885
TI  - The use of demucosalized bowel to augment small contracted bladders.

PMID- 9772884
TI  - Hydrolysis of androgen receptor by cathepsin D: its biological significance in
      human prostate cancer.
AB  - OBJECTIVE: To elicit the biological role of a lysosomal protease, cathepsin D
      (CatD) in prostate cancer, by investigating its regulatory effect on the androgen
      receptor (AR) using human prostate cancer LNCaP cells and prostate tissue
      specimens. MATERIALS AND METHODS: Cell extracts were prepared from LNCaP or
      prostate specimens by cell lysis and tissue homogenization. Proteolytic assays
      were performed by incubating these extracts in acidic buffer (pH 3-4) at 37
      degrees C. The resulting effects on AR and CatD were then analysed using Western
      immunoblots. RESULTS: The Western blots showed that AR was virtually hydrolysed
      with acid treatment, because endogenous CatD was activated; this activation only
      occurred at pH 3.2-3.5, but no specific acid appeared to be required. Further
      analyses suggested that CatD activation could be attributed to acid-induced
      autoproteolysis of mature CatD. Similar assays were also performed on prostate
      tissues, including normal and malignant specimens. These studies revealed that
      CatD-mediated AR hydrolysis was observed only in cancer specimens, while no such
      hydrolysis occurred in normal specimens. CONCLUSION: Endogenous CatD can
      hydrolyse AR, thereby possibly modulating AR function/metabolism in LNCaP cells,
      and in cancer specimens. CatD activity also appears to differ significantly
      between normal and malignant tissue. Thus, CatD may play a pivotal role as a
      growth modulator in androgen-dependent prostate cancer.

PMID- 9772886
TI  - Talc sclerotherapy for hydroceles.

PMID- 9772887
TI  - Idiopathic retroperitoneal fibrosis treated with tamoxifen only.

PMID- 9772888
TI  - Mucocele of the appendix: an unusual cause of obstructive kidney failure.

PMID- 9772890
TI  - Potential difficulty with extirpation of seminoma after orchidopexy with scrotal
      transposition (Ombredonne procedure).

PMID- 9772889
TI  - Large seminal vesicle cyst obstructing the ureter of a solitary kidney.

PMID- 9772892
TI  - Chest wall abscess after ureteric stent insertion.

PMID- 9772891
TI  - Systemic candidiasis presenting with prostatic abscess.

PMID- 9772893
TI  - Duplication of the urethra with posterior urethral enlargement mimicking
      posterior urethral valves.

PMID- 9772894
TI  - Urethral polyp in a young girl.

PMID- 9772895
TI  - Bladder diverticulum as an unusual content of a femoral hernia.

PMID- 9772896
TI  - Colonic metaplasia in prolapsed bladder mucosal grafts.

PMID- 9772898
TI  - Transversely tubularized ileal segments for the Mitrofanoff or Malone antegrade
      colonic enema procedures: the Monti principle.

PMID- 9772897
TI  - Clinical review of 100 consecutive surgically treated patients with upper tract
      transitional tumours.

PMID- 9772899
TI  - Gross calcification within the prostate gland.

PMID- 9772900
TI  - Is the timing of post-vasectomy analysis important?

PMID- 9772901
TI  - Does incision of the tunica vaginalis during the Palomo procedure prevent
      postoperative hydrocele?

PMID- 9772902
TI  - Isolation of yeast artificial chromosomes containing the entire transcriptional
      unit of the human FGF1 gene: a 720-kb contig spanning human chromosome 5q31.3-
      >q32.
AB  - The q31-q33 region of chromosome 5 includes a number of genes encoding growth
      factors, growth factor receptors, and hormone/neurotransmitter receptors. The
      human fibroblast growth factor 1 locus (FGF1) resides in this region of
      chromosome 5, which is frequently lost in myelodysplastic syndromes and acute
      myeloid leukemia patients. Other disease loci, including the loci for limb-girdle
      muscular dystrophy and an autosomal dominant deafness, have been mapped on this
      region, but their genes have not been isolated. It was shown that the critical
      region lost in two patients with the 5q- syndrome resides between FGF1 and IL12B.
      We previously reported the construction of a yeast artificial chromosome (YAC)
      contig spanning 330 kb around the FGF1 gene. Here we report the isolation of
      additional YAC clones that extend 290 kb from the previous contig. Sequence
      tagged sites developed from the outermost YAC ends were utilized in the contig
      cloning of two P1 clones P1Y2 and P1Y8. Together, these YAC and P1 clones span
      720 kb around the FGF1 locus. With the use of fluorescence in situ hybridization,
      a physical map has been constructed of these P1 and GRL (glucocorticoid receptor
      locus) probes on metaphase and interphase chromosomes. On the basis of our work
      and the known orientation of GRL transcription, the determined order of these
      loci on chromosome 5q31.3-q32 is centromere-P1Y8-3'[FGF1]5'-P1Y2-5'[GRL]3'-telome
      re. Knowing the transcriptional orientation of the FGF1 gene relative to the
      centromere will now facilitate the directional cloning of clinically important
      genes that may reside in this region.

PMID- 9772903
TI  - Interphase cytogenetics of esophageal adenocarcinoma and precursor lesions.
AB  - Limited information is currently available on chromosomal abnormalities in
      esophageal adenocarcinoma and associated premalignant lesions. In this study,
      numeric changes affecting chromosomes 4, 6, 7, 8, 9, 10, 11, 12, 17, 18, X, and Y
      were analyzed by using fluorescence in situ hybridization (FISH) with chromosome
      specific centromere DNA probes in 12 esophageal adenocarcinomas. In addition,
      TP53 overexpression, measured by immunohistochemistry, and amplification of HER
      2/neu and C-MYC, detected by FISH, were analyzed within the same tumors. The most
      common numeric abnormalities detected were gains of chromosomes 12 (8 cases), 6
      (7 cases), 7 (7 cases), and 11 (6 cases). The total number of abnormal
      chromosomes varied from 0 to 10, with an average of 4.6 per case. Overexpression
      of TP53 was present in 9 of 12 cases. No correlation was noted between the degree
      of aneusomy and TP53 overexpression. In contrast, HER-2/neu amplification was
      present in two cases, both with large numbers of aneusomic chromosomes.
      Amplification of C-MYC was detected in only one case that had a moderate number
      of numeric abnormalities. In a subset of cases in which premalignant lesions were
      examined, aneusomy was found to be an early change, frequently present in both
      Barrett's esophagus and dysplastic regions. In contrast, gene amplification and
      TP53 overexpression were restricted to more advanced areas of dysplasia and
      malignancy. Screening larger cohorts of patients with Barrett's esophagus or
      dysplasia for numeric abnormalities of chromosomes 6, 7, 11, and 12 may determine
      whether any of these abnormalities are predictive markers of progression to
      malignancy.

PMID- 9772904
TI  - Expression of reciprocal fusion transcripts of the HMGIC and LPP genes in
      parosteal lipoma.
AB  - Parosteal lipomas are rare benign neoplasms of adipose tissue that exhibit a
      contiguous relationship with the periosteum. These lipomas of the bone share some
      histopathologic features with their commonly occurring soft tissue counterparts.
      The latter are well-characterized cytogenetically, primarily by rearrangements
      involving chromosome region 12q13-q15. In particular, translocations involving
      12q13-q15 are prominent, with chromosomal region 3q27-q28 as the most frequent
      translocation partner. Recently, we established that the genes HMGIC at 12q15 and
      LPP at 3q27-28 are affected by the 3;12-translocation and demonstrated that, as a
      direct result, HMGIC/LPP and LPP/HMGIC fusion transcripts are expressed in soft
      tissue lipomas. In this study, cytogenetic and molecular analyses revealed
      similar findings in a parosteal lipoma. Specifically, a t(3;12)(q28;q14) was
      detected cytogenetically in a parosteal lipoma from a 51-year-old female and
      subsequently confirmed by FISH utilizing a chromosome 3 breakpoint spanning YAC
      probe and chromosome 12 breakpoint flanking cosmid probes. RT-PCR analysis showed
      expression of HMGIC/LPP and LPP/HMGIC fusion transcripts in this parosteal
      lipoma; nucleotide sequence analysis revealed that these transcripts are
      identical to those expressed in soft tissue lipomas characterized by a 3;12
      translocation. These findings lend further support to a common histopathogenesis
      between lipomas of soft tissue and parosteal origin.

PMID- 9772905
TI  - Characterization of multiple 12p rearrangements in testicular germ cell tumor
      cell line 833K and its subclone 64CP by chromosome microdissection.
AB  - Rearrangements of chromosome arm 12p are known to be common in germ cell tumors
      (GCT). Previous studies, using fluorescence in situ hybridization (FISH) with a
      whole chromosome 12 painting probe, showed unusual distributions of chromosome 12
      derived chromatin in GCT cell line 833K and its cisplatin-resistant subclone,
      64CP, located next to AgNOR (silver staining nucleolus organizer regions), some
      of which were ectopic. In this study, the ectopic stalk regions were shown by
      FISH to be composed of 18s and 28s rDNA, but were flanked by beta-satellite DNA,
      which may form a barrier around the rDNA. In order to determine the specific
      origins of the rearranged chromosome 12 segments, three different derived
      chromosome 12 regions were isolated from 64CP, using chromosomal microdissection.
      The microdissected fragments were labeled and hybridized by FISH to normal human
      chromosomes. All three segments localized to distal 12p; 12p12-->12pter, but with
      apparently different breakpoints for each segment. Furthermore, three-color FISH
      experiments with 12p band-specific probes demonstrated that the derivative
      chromosome 12 regions in 833K also originate from distal 12p (12p12-->p13). These
      sequences now can be evaluated for degree of overlap or common breakpoints which
      may be of significance in the development or progression of GCT.

PMID- 9772906
TI  - Comparative genomic hybridization analysis of human parathyroid tumors.
AB  - Primary hyperparathyroidism is characterized by hypercalcemia and elevated
      parathyroid hormone levels. It can be caused by overactivity of one (adenoma or
      carcinoma) or more (hyperplasia or multiple adenoma) parathyroid glands.
      Parathyroid adenoma and hyperplasia are usually mono- or oligoclonal neoplasms.
      To establish whether parathyroid cancer has a genetic composition distinct from
      parathyroid adenoma, we analyzed 10 adenoma and 10 carcinoma cases by comparative
      genomic hybridization (CGH). Results show clear differences between the
      constitution of adenoma and carcinoma genomic DNA. The most frequent genomic
      alterations in adenoma included deletions on chromosomes 11, 17 (5 of 10 cases),
      and 22 (7 of 10 cases). In parathyroid carcinoma, frequent chromosomal deletions
      were on chromosome arm 1p (4 of 10 cases) and chromosome 17 (3 of 10 cases), and
      gains were on chromosome 5 (3 of 10 cases). Our data indicate that different
      genetic changes could contribute to the development of parathyroid adenoma and
      carcinoma; genomic losses predominate in adenoma, and gains along with some
      losses are found in carcinoma. Furthermore, the CGH results implicate several
      chromosomal regions that may harbor genes that could be potentially involved in
      the development of parathyroid adenoma and carcinoma.

PMID- 9772907
TI  - Translocation (11;14)(q13;q32) and overexpression of cyclin D1 protein in a CD23
      positive low-grade B-cell neoplasm.
AB  - We describe a case of low-grade B-cell neoplasm with features overlapping between
      B-chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). The patient
      presented with a 10-year history of stable CLL without any treatment. The
      peripheral-blood picture was consistent with atypical mixed CLL (French-American
      British criteria), whereas the lymph-node histology was more consistent with MCL.
      Neoplastic cells were strongly positive for surface immunoglobulin M, kappa, CD5,
      CD20, CD23, and cyclin D1. Expression of CD11c was weak. Translocation (11;14)
      and der(10)t(10;?)(p11;?) were the primary cytogenetic changes observed in both
      peripheral blood (47%) and lymph node (7%). Trisomy 12 was absent. Deletion 6q21
      and rearrangements involving 1p/q, consistently associated with progression in
      lymphomas, also were noted in the peripheral blood but were nonclonal. The
      present case and similar cases with features overlapping between CLL and MCL most
      likely represent hybrids. In cases with features of typical CLL, t(11;14) is
      probably associated with gradual progression and may precede clinical and
      histologic transformation.

PMID- 9772908
TI  - Cytogenetic studies in patients from India with T-acute lymphoblastic leukemia.
AB  - Cytogenetic analysis was performed in 30 patients with T cell acute lymphoblastic
      leukemia (11 adults, 19 children) at initial presentation and analysis was also
      repeated in clinical and hematological remission in 15 patients. At initial
      presentation, chromosomal abnormalities were detected in 27 cases (90%) and
      hypodiploidy was detected in 19 patients (63.3%), followed by pseudodiploidy in
      six patients (20%) and hyperdiploidy in two patients (6.6%). Other karyotypic
      abnormalities detected were deletion 6q (40%), deletion 11 q (16.6%), deletion 7q
      (10%), abnormalities of chromosome 9 in (13.3%) and translocation
      t(11;14)(p13;q11) in 6.6% and der(12)t(12;?)(p13;?) in (3.3%). In complete
      remission, nine out of 15 cases (60%) showed chromosomal aberrations. Original
      abnormalities were detected in two cases (13.3%) and new abnormalities were
      detected in seven cases (46.6%).

PMID- 9772909
TI  - A clinically aggressive, polymorphic, polyclonal posttransplantation
      lymphoproliferative disorder.
AB  - Posttransplantation lymphoproliferative disorders (PTLD) have been divided, based
      on morphology, into polymorphic and monomorphic types, since findings in the
      literature reveal that polymorphic PTLD more likely responds to reduced
      immunosuppression. We report a clinically aggressive, polymorphic (and
      polyclonal) PTLD despite reduced immunosuppression and discuss possible
      therapeutic options. In addition, our case suggests that cytogenetic studies may
      be useful in determining prognosis when DNA molecular techniques do not detect
      monoclonality.

PMID- 9772910
TI  - Stability of microsatellites in myeloid neoplasias.
AB  - Microsatellites are short, repeated DNA sequences that exist throughout the
      genome. Instability of these sequences, associated with defects in the DNA
      mismatch repair system, is the hallmark of hereditary non-polyposis colorectal
      cancer (HNPCC), and is also found in many sporadic cancers. Although many types
      of solid tumors exhibit this type of genetic instability, its involvement in
      hematologic cancers is less evident. We have investigated whether microstatellite
      instability (MSI) is involved in the transformation of myeloid cells to
      myelodysplastic syndrome (MDS) and/or acute myelogenous leukemia (AML). Both de
      novo and treatment-associated neoplasias were studied. Only one example of MSI
      was found in 48 patients, using a panel of 14 different microsatellite loci
      consisting of repeats of one to four base pairs. These results suggest that the
      genes responsible for MSI are not involved in the transformation of normal
      myeloid cells to MDS or AML.

PMID- 9772911
TI  - Comparative genomic hybridization reveals differences in DNA copy number changes
      between sporadic gastric carcinomas and gastric carcinomas from patients with
      hereditary nonpolyposis colorectal cancer.
AB  - Comparative genomic hybridization was used to search for DNA copy number changes
      in samples of gastric cancer from 12 hereditary nonpolyposis colon cancer (HNPCC)
      patients and in samples of sporadic gastric carcinoma from 13 patients. The
      gastric cancer samples from HNPCC patients showed gains affecting 19q, Xp, and
      whole chromosome 22, each in a single patient. Neither high-level amplifications
      nor losses of DNA copy number were detected. On the other hand, 10 of the 13
      (77%) sporadic gastric carcinoma samples had multiple DNA copy number changes.
      The most frequent gains occurred with minimal common overlapping regions at 1q22
      q31, 8q23-qter, 17p11.2-q22, and 20q, all at a frequency of 31%. High-level
      amplifications were also seen at 17q21 in three cases (23%). Losses were rare,
      and the most frequent loss was with a minimal common overlapping region at 4q32
      (23%). This suggests that multiple DNA copy number changes are needed for the
      development of sporadic gastric carcinoma but not for gastric carcinoma in HNPCC
      patients.

PMID- 9772912
TI  - Cytogenetic analysis of colorectal adenomas: karyotypic comparisons of
      synchronous tumors.
AB  - The phenotypic progression of colorectal tumors is driven by their step-by-step
      acquisition of genomic alterations. These pathogenetically important mutations
      are at the same time markers of tumor clonality. The aim of this study was to
      describe the clonal relation among synchronous colorectal adenomas. Twenty-four
      colorectal adenomas from 11 patients were subjected to chromosome banding
      analysis. Clonal chromosome abnormalities were found in 20 tumors. Recurrent
      structural rearrangements involved chromosomes 1, 13, 17, and 18. The most common
      numerical changes were gain of chromosomes 7, 13, 20, and 3 and loss of
      chromosome 18. Eight adenomas had subclones as evidence of clonal evolution.
      Similar clones in separate polyps were seen in tumors from 6 patients; these
      adenomas were always located in the same part of the large bowel. In 2 patients,
      both with one rectal adenoma and one adenoma in the colon, no karyotypic
      similarity between the lesions was found. Our findings indicate that whereas
      close, but macroscopically distinct, synchronous colorectal adenomas usually have
      a common pathway of progression, perhaps even the same clonal origin, large bowel
      adenomas at a considerable distance from one another exhibit karyotypic
      differences, indicating that they arise independently.

PMID- 9772913
TI  - Translocation (1;22) in refractory anemia and the prognostic significance of
      karyotypic abnormalities in refractory anemia.
AB  - The most common cytogenetic abnormalities associated with myelodysplastic
      syndromes are deletions of chromosomes 5 and 7 and trisomy 8. Reciprocal
      translocation is relatively uncommon in refractory anemia. We describe a case of
      refractory anemia associated with trisomy 8 and a derivative chromosome 22
      resulting from t(1;22)(q11;q11.2). The diseases and the role of the various genes
      that are mapped to these breakpoints are discussed. The prognostic significance
      of karyotypic abnormalities in refractory anemia are reviewed.

PMID- 9772914
TI  - 47,XYY karyotype in acute myeloid leukemia.
AB  - A case of acute myelomonocytic leukemia (AMMoL; M4) with a 47,XYY karyotype is
      reported. This chromosome aneuploidy was found in both bone marrow cells and
      mitogen-stimulated lymphocytes. The contribution of XYY chromosomal constitution
      in the pathogenesis of AMMoL is controversial.

PMID- 9772915
TI  - A novel translocation (1;2)(p34;p21-22) in acute myelomonoblastic leukemia.
AB  - A novel and as yet unrecorded translocation, (1;2)(p34;p21-22), detected in a
      patient with acute myeloid leukemia (AML) is reported. The leukemia--in this
      case, AML-M4--showed a rapidly progressive fatal course despite an early
      transient response to aggressive chemotherapy. In this patient, the leukemic
      cells showed a novel balanced translocation, (1;2)(p34;p21-22), in most of the
      metaphases at the time of diagnosis and during subsequent relapse. Interferon
      inducible double-stranded RNA-dependent protein kinase (ds RNA-PK) is located in
      the chromosome region, 2p21-22, that was involved in the translocation in this
      case. The possible role of ds RNA-PK in leukemogenesis is briefly mentioned.

PMID- 9772916
TI  - Increased C-MYC oncogene copy number detected with combined modified comparative
      genomic hybridization and FISH analysis in a Richter syndrome case with complex
      karyotype.
AB  - Modified comparative genomic hybridization (mCGH) was performed in a Richter
      syndrome case with a complex karyotype to identify and map gains of DNA sequences
      with possible importance in the pathogenesis and progression of the tumor. The
      mCGH analysis revealed a more intense signal on part of the long arm of one pair
      of chromosomes belonging to group C. The G-banding study showed that the
      increased DNA-sequence copy number originated from the 8q22-->qter chromosomal
      region. This increase was confirmed by performing a fluorescence in situ
      hybridization analysis on tumor metaphases by first using a chromosome 8-specific
      library and subsequently a C-MYC probe, which revealed positive staining on six
      different regions located on six different chromosomes, each one bearing a single
      copy of the C-MYC oncogene. These results show the existence of C-MYC oncogene
      copy-number increases and confirm the usefulness of mCGH in the genetic analysis
      of malignancies.

PMID- 9772917
TI  - Isochromosomes 7q and 17q in Wilms tumor.
AB  - We report the cytogenetic findings in a Wilms tumor from a 4-year-old boy.
      Karyotypic analysis revealed isochromosomes of 7q and 17q as coexisting clonal
      aberrations. The finding is notable in view of recent reports of i(7q) as a
      nonrandom event in Wilms tumor and the emerging evidence for genetic
      heterogeneity in this tumor.

PMID- 9772918
TI  - Confirming the origin of add(9q) and marker chromosome in a case of acute
      monoblastic leukemia (M5b) by fluorescence in situ hybridization.

PMID- 9772919
TI  - Trisomy 16 as the primary chromosome aberration in a papilloma of the breast.

PMID- 9772920
TI  - Idiopathic chronic eosinophilic pneumonia. A clinical and follow-up study of 62
      cases. The Groupe d'Etudes et de Recherche sur les Maladies "Orphelines"
      Pulmonaires (GERM"O"P).
AB  - Idiopathic chronic eosinophilic pneumonia (CEP) is a rare disorder of unknown
      cause with nonspecific respiratory and systemic symptoms but rather
      characteristic peripheral alveolar infiltrates on imaging, developing mainly in
      women and in atopic subjects. The disorder is highly responsive to oral
      corticosteroid therapy, but relapses are frequent on reducing or stopping
      treatment. The long-term course of the disease and data regarding outcome,
      particularly the need for prolonged oral corticosteroid therapy and the
      development of severe asthma, are somewhat contradictory. A multicentric
      retrospective study was conducted in an attempt to describe better the initial
      features and, above all, the later course of CEP in a large homogeneous series of
      62 stringently selected patients of whom 46 were followed for more than 1 year.
      The prevalence of smokers was low (6.5%) and about half of our patients (51.6%)
      had a previous, and often prolonged, history of asthma. The clinical and
      roentgenographic features were in keeping with previous studies, but we found
      that computed tomography could disclose ground glass opacities not detected by X
      ray, and that migratory infiltrates before treatment were more frequent (25.5%)
      than reported previously. The bronchoalveolar lavage cellular count always showed
      a striking eosinophilic pattern, thus allowing distinction between CEP and
      cryptogenic organizing pneumonia, both syndromes sharing many common clinical and
      imaging features. About two-thirds of the patients (68%) showed a ventilatory
      defect in pulmonary function tests, with about one-half of these presenting with
      an obstructive pattern, sometimes without previous asthma. Along with the
      submucosal eosinophilic infiltration noted in 2 patients without ventilatory
      defect, this is strong evidence to confirm that CEP is not only an
      alveolointerstitial but also an airway disease. The dramatic response to oral
      corticosteroid therapy was observed in all treated patients. Although only 1
      patient initially treated for less than 6 months did not relapse, longer oral
      corticosteroid therapy in no way provided protection from further relapses. We
      thus propose to try to wean oral corticosteroid therapy after 6 months in
      patients without severe asthma, because recurrences remain responsive to oral
      steroids. However, prolonged oral corticosteroid therapy was necessary in the
      majority of patients, with 68.9% of those followed for more than 1 year still on
      oral corticosteroid therapy at the last follow-up, either because of relapse or
      because of severe asthma.

PMID- 9772921
TI  - Central nervous system infection with Listeria monocytogenes. 33 years'
      experience at a general hospital and review of 776 episodes from the literature.
AB  - We reviewed 776 previously reported and 44 new cases of CNS listeriosis outside
      of pregnancy and the neonatal period, and evaluated the epidemiologic,
      diagnostic, and therapeutic characteristics of this infection. Among patients
      with Listeria meningitis/meningoencephalitis, hematologic malignancy and kidney
      transplantation were the leading predisposing factors, but 36% of patients had no
      underlying diseases recognized. The infection occurred throughout life, with a
      higher incidence before the age of 3 and after the age of 45-50 years. Fever,
      altered sensorium, and headache were the most common symptoms, but 42% of
      patients had no meningeal signs on admission. Compared with patients with acute
      meningitis due to other bacterial pathogens, patients with Listeria infection had
      a significantly lower incidence of meningeal signs, and the CSF profile was
      significantly less likely to have a high WBC count or a high protein
      concentration. Gram stain of CSF was negative in two-thirds of cases of CNS
      listeriosis. One-third of patients had focal neurologic findings, and
      approximately one-fourth developed seizures over their course. Mortality was 26%
      overall, and was higher among patients with seizures and those older than 65
      years of age. Relapse occurred in 7% of episodes. Ampicillin for a minimum of 15
      21 days (with an aminoglycoside for at least the first 7-10 days) remains the
      treatment of choice. Cerebritis/abscess due to L. monocytogenes, without
      meningeal involvement, is less common but may be diagnosed by blood cultures and
      CNS imaging, or by stereotactic biopsy. Longer antibiotic therapy (at least 5-6
      weeks) is needed in the presence of localized CNS involvement.

PMID- 9772922
TI  - Infected cardiac myxoma. Case report and literature review.
AB  - We present a case of a left atrial myxoma infected with Porphyromonas
      asaccharolytica in a 55-year-old man, successfully treated with surgical excision
      and a brief course of antibiotic therapy. Infected cardiac myxomas are extremely
      rare, with only 39 cases previously reported. They can be difficult to diagnose
      due to their protean clinical manifestations, which can often be seen in
      uninfected myxomas as well. We suggest that blood cultures and careful pathologic
      examination be performed in all cases of cardiac myxoma with constitutional
      symptoms. However, fever and elevated sedimentation rate are significantly more
      common in infected tumors. Organisms responsible are similar in distribution to
      those causing bacterial endocarditis. Emboli, though frequent, may not be more
      common in infected than uninfected myxomas. Case reports have become more common
      since the development of better diagnostic techniques. Echocardiography,
      especially by the transesophageal approach, is the diagnostic procedure of
      choice, and sensitivity approaches 100%. Surgical excision is curative and
      generally has low morbidity and mortality.

PMID- 9772923
TI  - Aspergillus nidulans infection in chronic granulomatous disease.
AB  - Chronic granulomatous disease (CGD) is a rare inherited disorder of the NADPH
      oxidase complex in which phagocytes are defective in generating reactive
      oxidants. As a result, patients with CGD suffer from recurrent bacterial and
      fungal infections. The most common fungal infections are caused by Aspergillus
      species. Aspergillus nidulans is a rare pathogen in most patient populations with
      quantitative or qualitative neutrophil defects. We have reviewed all cases in
      which A. nidulans was isolated from patients at the National Institutes of Health
      (Bethesda, MD) between 1976 and 1997. A. nidulans infection occurred in 6
      patients with CGD, but was not a pathogen in any other patient group. Aspergillus
      fumigatus was a more common pathogen in CGD compared with A. nidulans, but A.
      nidulans was more virulent. A. nidulans was significantly more likely to result
      in death compared with A. fumigatus, to involve adjacent bone, and to cause
      disseminated disease. Patients with A. nidulans received longer courses of
      amphotericin B therapy than patients with A. fumigatus, and were treated with
      surgery more often. In contrast to A. fumigatus, A. nidulans was generally
      refractory to intensive antifungal therapy, suggesting that early surgery may be
      important. These data show that A. nidulans is a distinct pathogen in CGD and its
      isolation carries more severe implications than that of A. fumigatus.

PMID- 9772925
TI  - [Constrictive pericarditis: an underestimated complication of thoracic injuries].
AB  - Constrictive pericarditis is a well defined clinical entity, traditionally
      secondary to longstanding tuberculosis. Although posttraumatic constrictive
      pericarditis, due to haemopericardium, is well known during the postoperative
      period following cardiac surgery, it is underestimated in closed chest trauma. A
      new case of constrictive pericarditis is reported, due to neglected chest trauma.
      The discussion emphasizes the need for early diagnosis and surgical treatment,
      which determine the general prognosis of pericardial constriction. This implies
      systematic investigation of all cases of chest trauma, even minor, by
      transthoracic, or preferable, transoesophageal echocardiography, looking for
      haemopericardium.

PMID- 9772924
TI  - Outcomes of recipients of both bone marrow and solid organ transplants. A review.
AB  - In this review we examine the clinical outcomes of patients who have received
      both bone marrow transplantation (BMT) and solid organ transplantation (SOT) and
      discuss the possible immunologic consequences of the dual transplants. We
      collected cases through a comprehensive literature search (MEDLINE database,
      English literature only) covering the years 1990 through 1997 and correspondence
      with the International Bone Marrow Transplant Registry. Our study selected case
      reports of patients who have undergone both bone marrow and solid organ
      transplants; cases in which bone marrow transplantation was undertaken as an
      adjunct ot induce or augment donor-specific tolerance in a recipient to the
      transplanted organ were excluded. Clinical characteristics included patient's
      demographic information, underlying disorders for each transplant, source of
      donor organ or tissue, time between transplants, and immunosuppressive regimens
      used to prevent graft-versus-host disease (GVHD) or graft rejection. Clinical
      outcomes included patient survival, complications of transplantation, and donor
      specific tolerance that was experienced in many cases. Twenty-one cases of SOT
      after BMT and 7 cases of BMT after SOT were reviewed. Solid organ
      transplantations included lung, liver, cardiac, and kidney for a variety of BMT
      related complications including GVHD, hepatic veno-occlusive disease, chronic
      renal failure, end-stage pulmonary disease, and severe cardiomyopathy. Bone
      marrow transplants were performed following SOT for aplastic anemia and
      hematologic malignancies. Clinical outcomes for patients who received both BMT
      and SOT were variable and depended on transplant indication and degree of
      histocompatibility. Prior bone marrow transplantation may tolerize for a
      subsequent organ transplant from the same donor. Conversely, severe GVHD may
      follow BMT from human leukocyte antigen (HLA)-matched donors following SOT. The
      favorable survival in this high-risk group of patients may represent a literature
      review bias (that is, an undetermined number of unsuccessful cases may not have
      been reported). Nonetheless, dual transplantation is clearly feasible in selected
      cases.

PMID- 9772926
TI  - [Peripheral embolic arterial accident due to pulmonary vein thrombosis revealing
      bronchial carcinoma].
AB  - The authors report a case of left superior pulmonary vein thrombosis discovered
      on transoesophageal ultrasonography in the context of aetiological assessment of
      a systemic vascular accident. This unusual site of a thrombus on an anatomically
      perfectly normal left atrium led the authors to perform a more detailed
      assessment, revealing a previously undiagnosed lung cancer on thoracic CT scan.

PMID- 9772928
TI  - [Cardiac tamponade and transient ischemia revealing a syndrome of primary
      antiphospholipid antibodies].
AB  - The authors report a case of echocardiographically confirmed cardiac tamponade,
      which required emergency pericardial aspiration, and a transient ischaemic attack
      revealing an underlying primary antiphospholipid antibody syndrome in a 29-year
      old patient. The test for antiphospholipid antibodies was positive on 2 occasions
      (IgG > 91.41 micrograms/l). The diagnosis of systemic lupus erythematosus was
      eliminated. A favourable course was observed after 3 months of corticosteroids
      and platelet antiaggregants. Any case of cardiac tamponade or transient ischaemic
      attack with an unexplained aetiology in a young patient must suggest the
      diagnosis of antiphospholipid antibody syndrome.

PMID- 9772927
TI  - [Incidental discovery of a giant myxoma].
AB  - The authors report a case of very large myxoma of the left atrium, original in
      terms of its mode of discovery, its very calcified appearance, in a totally
      asymptomatic elderly patient. A complete ultrasound assessment, catheterization,
      and coronary angiography allowed assessment of the morphology, topography, blood
      supply and cardiac repercussions of this tumour. Myxoma of the left auricle is
      the commonest cardiac tumour, with multiple clinical features and presentations.
      This benign tumour arises from embryonic vestigial remains, usually in the fossa
      ovale. The present case is original by its unusual mode of discovery in a totally
      asymptomatic patient.

PMID- 9772929
TI  - [Antithrombotic agents in unstable angina. Review of clinical trials].
AB  - Antithrombotic treatment of unstable angina is a highly controversial subject.
      The development of new antithrombotics (anti Gp IIb-IIIa, hirudin) has led to
      numerous therapeutic trials. Anti Gp IIb-IIIa are very promising in this
      indication, especially the Reopro chimeric antibody (Abciximab). Hirudin and its
      derivatives have demonstrated an early, but ephemeral clinical benefit. Low
      molecular weight heparins appear to be more effective than non-fractioned heparin
      and are easier and safer to use.

PMID- 9772930
TI  - [Antihypertensive action and predictive factors of efficacy of benazepril in mild
      to-moderate hypertension: clinical trial in general medical practice on 16,987
      patients].
AB  - The aim of the study was to evaluate in general practice, in a large and
      unselected population of patients, the efficacy and safety of benazepril
      associated or not with hydrochlorothiazide (HCTZ) and to identify clinical and
      demographic predictive factors of antihypertensive efficacy. In this open
      uncontrolled study, 16,987 patients with mild to moderate hypertension were
      included by 5350 GPs. They received benazepril (BNZ) 10 mg once daily for 8
      weeks. If sitting DBP remained > 90 mmHg after 4 weeks, HCTZ 12.5 mg once a day
      was then added for the last 4 weeks. RESULTS: In the intent to treat analysis,
      54.5% of patients, after 4 weeks, and 80.6% of patients after 8 weeks, were
      controlled (DBP < 90 mmHg). Mean sitting DBP decreased from 100.5 +/- 5.5 mmHg
      (baseline) to 86.7 +/- 7.5 mmHg after 4 weeks and to 82.5 +/- 6.5 mmHg after 8
      weeks. Mean SBP decreased from 169.5 +/- 13.1 mmHg to 150.5 +/- 12.5 mmHg after 4
      weeks and to 145.0 +/- 10.9 mmHg after 8 weeks. Of the 16,900 patients included
      in the safety analysis, 853 (5.0%) dropped out of the study, 504 (3.0%) for
      adverse events (AE). The most frequent AE were: cough (3.5%), headache (0.9%),
      dizziness (0.8%), asthenia (0.6%) and nausea (0.5%). 13 deaths were observed
      during the study, mainly due to stroke or cancer. Six cases of raised serum
      creatinine level, 3 cases of angio-oedema and 2 cases of hepatitis were also
      reported. After 8 weeks of treatment, the main predictors of therapeutic response
      (DBP) were: recently discovered hypertension (86.3% of controlled DBP), regular
      exercise (85.5%) and age < 50 years (84.6%). Conversely: obesity, diabetes
      mellitus (77.9%), previously treated with several drugs (75.2%) and initial DBP >
      or = 105 mmHg (74.5%) were not predictive. Predictive factors emerging from
      logistic regression were : baseline DBP (< 105 mmHg), history of hypertension,
      body mass index, initial treatment of hypertension (no treatment--one drug-
      several drugs) and age. CONCLUSION: This large-scale study confirms, the
      antihypertensive efficacy and good tolerability of benazepril alone or associated
      with hydrochlorothiazide in general practice.

PMID- 9772931
TI  - [Intramural hematoma in the thoracic aorta: the "porous" aorta].

PMID- 9772932
TI  - [Cardiovascular risk and ambulatory blood pressure measurement of arterial
      pressure].
AB  - Many studies have demonstrated that elevation of blood pressure is proportional
      to the risk of developing cardiovascular accidents. The relationship between
      blood pressure and cardiovascular risk varies according to whether diastolic,
      systolic or pulse pressure is considered. Several other parameters are involved
      in the determinism of the blood pressure risk such as age, gender, ethnic group,
      etc. These elements emphasize the importance of considering the various blood
      pressures as well of the patient's risk factors and clinical characteristics for
      global evaluation of the cardiovascular risk. As blood pressure is an eminently
      variable parameter and as the essential element of evaluation of the blood
      pressure risk is based on its determination, it is important to measure blood
      pressure accurately and precisely. Clinical measurement of BP constitutes the
      reference method, but presents several limits and several causes of error which
      raise the problem of its validity to evaluate a given patient's mean blood
      pressure. Ambulatory blood pressure monitoring during 24 hours of usual activity
      appears to more accurately evaluate the blood pressure load likely to induce
      organic lesions, as several studies have demonstrated its superiority over
      occasional measurement to evaluate the risk and cardiovascular prognosis of HT.
      However, whether its application in the evaluation of the global cardiovascular
      risk and therapeutic management can improve the prevention strategy and long-term
      cardiovascular prognosis has yet to be determined.

PMID- 9772934
TI  - [Left ventricular hypertrophy and cardiovascular risk in hypertension].
AB  - Left ventricular hypertrophy (LVH) of hypertension is characterized by an
      increased ventricular mass due to myocardial cell hypertrophy and development of
      collagen and capillaries. Detected in man by electrocardiography and
      echocardiography, it is difficult to study due to the lack of sensitivity of EEG
      and the poor reproductibility of echocardiography, and by the lack of
      systematization of the analysis criteria adopted by investigators. Despite these
      uncertainties, the pejorative prognostic value of LVH has been clearly
      established and, based on its relationship with other risk factors, it can be
      considered to be an integrator of cardiovascular risk, justifying the use of this
      marker rather than other more variable indicators such as BP. The improved
      prognosis related to regression of LVH in response to treatment is currently
      controversial. Preliminary results indicate a reduction of morbidity-mortality in
      hypertensive patients when LVH is decreased; these findings must be confirmed
      before reduction of LVH can constitute an objective and antihypertensive
      treatment.

PMID- 9772933
TI  - [Arterial hypertension, non-drug treatment and cardiovascular risk].
AB  - Four non-drug measures have been shown to be effective on reduction of blood
      pressure: low-salt diet, weight loss, reduction of alcohol consumption and sports
      activity. Other measures, mainly dietary (increased potassium intake, DASH diet),
      may also be effective. The two limits to non-drug treatment of HT are the absence
      of demonstrated benefit in terms of cardiovascular morbidity-mortality, and the
      difficulty to ensure good patient compliance with this type of often constraining
      measure. However, these non-drug measures could probably decrease the overall
      level of cardiovascular risk. The main drawback, related to the required
      modification of the patient's lifestyle, is poor compliance with these measures.
      Compliance can be improved by various methods which share in common their time
      consuming nature.

PMID- 9772935
TI  - [The absolute cardiovascular risk: a valid but incomplete concept].

PMID- 9772936
TI  - [Efficacy and safety of indapamide 1.5 mg sustained release coated tablets in the
      therapy of arterial hypertension].
AB  - OBJECTIVE: In line with international recommendations concerning the need to
      decrease the doses of antihypertensives, a low dose form (1.5 mg) of indapamide,
      sustained release coated tablet (SR), has been developed in order to optimize the
      efficacy-safety ratio while maintaining a once daily dosage. The objective of
      this study was to evaluate the benefit obtained by reviewing the results of two
      clinical trials conducted according to a similar methodology. PATIENTS AND
      METHODS: European randomized double-blind trials were conducted in a total of 690
      hypertensive patients. The first trial was conducted in 285 patients treated for
      2 months and the second trial was conducted in 405 patients treated for 3 months.
      The second study was extended to 9 months under open-label conditions in order to
      obtain a follow-up of one year with clinical and ambulatory blood pressure
      monitoring. The average patient characteristics on inclusion were, in the two
      studies: age: 53 and 57 years, 44% and 57% of men, diastolic blood pressure
      (DRP): 100.6 and 102.5 mmHg, systolic blood pressure (SBP): 161.0 and 164.5 mmHg.
      RESULTS: The first dose-ranging study demonstrated the antihypertensive efficacy
      of indapamide 1.5 mg SR; the study second confirmed the equivalent efficacy with
      the 2.5 mg immediate release form of indapamide and a greater than 50% reduction
      of the number of patients presenting a serum potassium less than 3.4 mmol/l. The
      long-term study verified the absence of therapeutic escape. Clinical safety data
      assessed the absence of effects of indapamide on carbohydrate and lipid
      metabolism. CONCLUSION: Indapamide 1.5 mg sustained release coated tablet
      presents an optimized antihypertensive efficacy/safety ratio in line with
      international recommendations concerning the use of low-dose antihypertensives
      and diuretics as first-line treatment for hypertension.

PMID- 9772937
TI  - [Consideration of the risk of decision to treat hypercholesterolemia].

PMID- 9772938
TI  - [Polymorphous ventricular tachycardia occurring three months following
      radiofrequency ablation of the bundle of His].
AB  - The authors report the case of a 73-year-old patient presenting with polymorphous
      ventricular tachycardias one to 3 months after radiofrequency His bundle
      resection, as soon as the pacing frequency was reduced to 70 bpm. The clinical
      history revealed the existence of a possible clinical predisposition, as this
      patient had experienced an episode of torsade de pointe induced by
      hydroquinidine, one year previously. This case illustrates the importance of
      selecting a sufficiently high minimal stimulation frequency after His bundle
      resection.

PMID- 9772939
TI  - [Picture of the month: Kussmaul pulse].

PMID- 9772940
TI  - [Alteration of sinus variability after cardiac surgery].
AB  - Sinus tachycardia is frequent after cardiac surgery and this tachycardia is
      probably due to changes of the autonomic nervous system. The objective of this
      study was to evaluate the changes possibly induced by cardiac surgery, by
      studying sinus variability (SV) during a 24-hour Holter monitoring. The
      examination was performed in 28 patients who had undergone cardiac surgery 1 to 6
      weeks previously. These patients had no alteration of left ventricular function,
      or any causes likely to modify SV and they had a normal postoperative course.
      Their results were compared to those of 4 subjects developing a postoperative
      complication (1 case of ventricular tachycardia and 3 cases of resuscitated
      cardiac arrest). The results were also compared to those of 24 age-matched adult
      controls without heart disease (control group). The study of SV included temporal
      and spectral analysis of SV with measurement of the standard deviation of normal
      RR intervals (SD), mean heart rate (HR), percentage of RR intervals differing by
      more than 50 m/sec from the adjacent interval (pNN50), coefficient of variability
      (CV) (SD/RR), square root of the differences between successive RR (rMSSD),
      spectral properties of low frequencies (LF) and high frequencies (HF) and the
      fractionated spectral property (LF/HF). RESULTS: (see tables, page 151 and 152).
      An alteration of SV was therefore observed in the surgical group, and lasted 4 to
      6 months after surgery. No difference was observed between subjects without
      cardiac events and those presenting a cardiac event. IN CONCLUSION: cardiac
      surgery decreases all parameters of SV during the first few postoperative months.
      Certain unexpected cardiac accidents during this period could be explained by
      these changes.

PMID- 9772941
TI  - [Hypertension and Takayasu disease. Report of 8 cases].
AB  - In this paper, the authors report 8 cases of Takayasu disease presenting in the
      form of hypertension, observed in the Cardiology of Ibn Rochd University Hospital
      in Casablanca between 1983 and 1995. The majority of cases presented with
      renovascular HT, secondary to unilateral or bilateral renal artery stenosis. More
      rarely, the patients presented proximal hypertension secondary to coarctation of
      the aorta. Medical treatment was prescribed all 8 cases, associated with surgery
      in 8 cases.

PMID- 9772942
TI  - [Coronary vessel ectasia: coronary artery disease with a high thromboembolic
      risk].
AB  - Coronary dystrophy is characterized by the presence of successively stenotic and
      ectatic or even aneurysmal zones in the coronary network. The authors report a
      new case of coronary ectatic dystrophy presenting in with myocardial infarction.
      They review the literature and suggest the various aetiologies, the main one
      being atherosclerosis. The management of this particular form of atherosclerosis
      is dominated by the thromboembolic risk related to these aneurysmal zones
      responsible for myocardial infarction, justifying long-term anticoagulant
      therapy.

PMID- 9772943
TI  - [Cardiac metastasis of chondrosarcoma: a case report].
AB  - Chondrosarcoma is a primary malignant bone tumour which only exceptionally
      metastasises to the heart. We report a case of chondrosarcoma with left
      intracavitary cardiac metastasis discovered following abnormal cardiac
      auscultation. To our knowledge, only 21 cases have been described in the
      literature. A lesion of the right atrium is the most frequent event. The major
      risk of these tumours is their emboligenic properties: pulmonary embolism for
      metastases of the right heart, systemic embolism for metastases of the left
      heart. Echocardiography establishes the diagnosis by specifying the site and
      extent of the tumour. CT scan allows local assessment of the lesions. The course
      is fatal, although surgery has been able to increase survival of patients with
      isolated cardiac mestastases.

PMID- 9772944
TI  - [Study of the efficacy and safety of fosinopril in general practice in 19,435
      hypertensive patients (FLIGHT Study)].
AB  - The efficacy and good safety of fosinopril, an angiotensin converting enzyme
      inhibitor recently made available to the medical profession in France, has been
      demonstrated by several controlled studies versus placebo and reference
      antihypertensives. A phase IV multicentre clinical trial was conducted among
      general practitioners in order to assess, on a larger scale and under conditions
      of daily practice, the results obtained in terms of blood pressure control and
      quality of life as well as the clinical and laboratory safety of the drug. This
      analysis was based on 19,435 hypertensive patients, 989 of whom were over the age
      of 75 years, followed for 12 weeks after introduction of fosinopril either as
      monotherapy or in combination with the antihypertensive treatment(s) already
      prescribed. Under these conditions, after 12 weeks of treatment, blood pressure
      was controlled in 79.8% of patients, with improvement of all items of the quality
      of life scale. The very low incidence of clinical and laboratory adverse events,
      even among the oldest patients, confirms the safety of use of fosinopril,
      predictive of good long-term compliance with treatment.

PMID- 9772945
TI  - [Predictive factors of smoking cessation after myocardial infarction. Review of
      the literature].
AB  - This paper reviews the current state of knowledge about smoking after myocardial
      infarction in smokers. After presenting results emphasizing the value of post
      infarction smoking cessation, all of the predisposing factors to smoking
      cessation are analysed. The objective of this review of the literature is to
      recognize these factors in order to more precisely define the various medical,
      psychological and social aspects of an assistance programme adapted to post
      infarction smoking cessation.

PMID- 9772946
TI  - [Benefit of smoking cessation in therapeutics].

PMID- 9772947
TI  - [Study of the pharmacodynamic activity of daflon 500 mg].
AB  - Daflon 500 mg, micronized purified flavonoid fraction, composed of 90% diosmin
      and 10% hesperidin, possesses venotonic and vasculoprotective pharmacological
      properties, it reinforces venous tone by prolonging the activity of parietal
      norepinephrine. The pharmacodynamic properties of Daflon 500 mg were demonstrated
      by mercury stress gauge venous occlusion plethysmography during a double-blind
      placebo-controlled trial in 10 women not presenting any venous disease. Venous
      tone was significantly reinforced by the 1st hour after a single dose of 2
      tablets of Daflon 500 mg. This effect persisted for 4 to 24 hours according to
      the mode of administration. The rapid action of Daflon 500 mg is due to
      micronization of its active ingredient into particles less than 2 microns,
      thereby considerably increasing its absorption.

PMID- 9772948
TI  - [Late potentials].

PMID- 9772949
TI  - [Supraventricular arrhythmia after pneumonectomy. Apropos of 100 cases and review
      of the literature].
AB  - Supraventricular arrhythmias are frequently observed in pneumonectomy surgery. We
      retrospectively studied a series of 100 consecutive patients undergoing
      pneumonectomy for cancer between 1994 and 1996. We found 24% of significant
      supraventricular arrhythmias, corresponding to atrial fibrillation in 75% of
      cases, occurring in 80% of cases until the third postoperative day. The only risk
      factor significantly associated with these arrhythmias was the patient's age.
      These arrhythmias are easily reduced, spontaneously in 25% of cases, and usually
      by amiodarone, alone or associated with digitalis alkaloids. While the mortality
      of the overall group was 12%, 8% of patients with arrythmia died. These deaths
      concerned patients whose arrythmias occurred after the fourth postoperative day
      in a context of a pulmonary infection.

PMID- 9772950
TI  - [Evaluation of high amplification ECG and the study of sinus variability in the
      detection of patients at risk of sudden death].
AB  - In order to define the best strategy of prognostic evaluation in relation to
      patients in heart failure, 415 patients with impaired left ventricular function
      (ejection fraction < 40%) were prospectively included, between June 1993 and
      1996, in a study comparing the respective value of high amplification ECG and
      Holter analysis of sinus variability, 308 patients in sinus rhythm and narrow QRS
      complexes were included. The patients were distributed into 4 groups according to
      the presence or absence of late potentials and altered sinus variability (group I
      with 2 normal examinations, group II with late potentials and normal variability,
      group III without late potentials, but with altered variability and group IV with
      2 abnormal examinations). The sudden and overall mortality was significantly
      greater in groups III (28 and 11%) and IV (28 and 9%) than in group I (7 and 3%)
      and II (11 and 2%). The presence of potential was unable to identify patients at
      risk of ventricular tachycardia and sudden death. In another 60 patients with
      complete branch block, the prognosis was also correlated with the alteration of
      sinus variability. In conclusion, high amplification ECG correctly evaluated the
      prognosis of subjects in heart failure. However, analysis of sinus variability
      should be systematically proposed to detect subjects at high risk of mortality,
      whether the subject has large or narrow QRS complexes.

PMID- 9772952
TI  - [Incidental CT discovery of an isolated thrombus in the aortic arch].
AB  - The authors report a case of isolated thrombus of the aortic arch discovered
      incidentally during thoracic CT angiography, complicated by clinical features of
      embolic renal infarction despite introduction of anticoagulant treatment. This
      case confirms the value of transoesophageal echocardiography to diagnose and
      follow these lesions and illustrates the therapeutic approach following discovery
      of aortic thrombi.

PMID- 9772951
TI  - [ECG anomalies and axis deviations in heart transplant recipients: MRI studies].
AB  - The electrocardiogram is often abnormal after orthotopic cardiac transplantation.
      This study was conducted in order to evaluate the frequency of these
      abnormalities in a population of 29 patients transplanted according to the
      conventional mode or the total mode. We also investigated the correlation between
      these abnormalities and the presence of left ventricular hypertrophy or deviation
      of the left ventricular long axis. The left ventricular mass was measured by TM
      echocardiography. The position of the left ventricular long axis was determined
      by MR on a ultrarapid sequence. The ECG was normal in 5 patients. The
      abnormalities revealed in the other 24 patients were: an rSr' or rsr' appearance
      in V1 with a QRS complex less than 0.12 sec in 11 patients, complete right block
      in 1 patients, repolarization abnormalities (apart from those associated with
      branch blocks) in 8 patients, left axis deviation of the QRS in 5 patients, a
      biphasic P wave in V1 with a Morris index greater than 4 mV.sec in 5 patients,
      and double atrial activity in 3 patients. These abnormalities were observed
      regardless of the type of transplantation, with the exception of double atrial
      activity which was only observed in the group of patients undergoing conventional
      transplantation. On average, the long axis of the left ventricle was more
      horizontal and deviated to the left compared to age- and sex-matched controls.
      All patients with left axis deviation of the QRS had left ventricular hypertrophy
      versus 13 of the 24 patients without QRS axis deviation and abnormalities of
      position of the anatomical left ventricular long axis. Our results therefore
      suggest that the frequent presence of right branch block in heart transplant
      recipients is due to factors other than the position of the heart in the thorax,
      for example right ventricular hypertrophy.

PMID- 9772953
TI  - [Contribution of ischemia tests in stress echocardiography].
AB  - This paper, concerning a noninvasive technique of investigation of ischaemic
      heart disease, developed in the United States more than ten years ago, describes
      the various indications of this technique, continuously up-dated by new
      publications. It reports the results of the main studies already conducted on the
      detection of myocardial ischaemia. Because of the abundant data on this subject,
      the applications of stress echocardiography in the field of myocardial viability
      were deliberately not discussed here.

PMID- 9772954
TI  - [Abciximab-induced thrombopenia during treatment of acute coronary syndromes by
      angioplasty].
AB  - ReoPro (abciximab) is the Fab fragment of a chimeric monoclonal antibody directed
      against platelet glycoprotein IIb-IIIa. Its efficacy to prevent ischaemic
      complications after PTCA has been demonstrated in 3 studies: EPIC, EPILOG,
      UPTAKE. One hundred and sixty five cases of thrombocytopenia (<
      100,000/microliter) were reported in a series of 5461 patients randomized in
      these 3 studies (i.e. 3.0%), including 46 (2.03%) with placebo and 119 (3.73%
      with abciximab. Among the 2270 patients randomized to receive placebo, 11 (0.48%)
      cases of severe thrombocytopenia (< 50,000/microliter) were observed versus 34
      (1.07%) with abciximab. Major acute thrombocytopenia (< 20,000/microliter and <
      24 hours) occurred in 0.60% (20 patients) of cases with abciximab. Their
      mechanism remains unknown. A therapeutic challenge did not modify either their
      incidence, or their severity. The development of thrombocytopenia did not worsen
      the patient's prognosis and course was always favourable. Twenty five cases of
      thrombocytopenia (0.60%), including 3 cases of acute major thrombocytopenia
      (0.08%) were spontaneously reported in France among the first 4000 patients
      treated with abciximab post-marketing. All patients treated with abciximab must
      be monitored by platelet count, 2 to 4 hours after the bolus administration, then
      12 and 24 hours later. These platelet counts should be performed on 3 tubes
      (EDTA, citrate, heparin) in order to eliminate pseudothrombocytopenia and a
      differential diagnosis. In the case of true thrombocytopenia (< 10,000/l),
      treatment should be suspended and the platelet count should be repeated daily
      until return to normal. In the case of thrombocytopenia less than
      60,000/microliter, heparin and aspirin should also be systematically discontinued
      and, below 50,000/microliter, platelet transfusion is justified.

PMID- 9772955
TI  - [Picture of the month. Reduction of heart rate variability after myocardial
      infarct].

PMID- 9772956
TI  - [Heart rate: relative risk and absolute risk].
AB  - The concept of the threshold of therapeutic intervention as a function of the
      absolute risk is introduced. The definitions of relative risk and absolute risk
      are then recalled; in the case of absolute risk, only prolonged observation of a
      cohort combined with multivariate statistical analysis can select the most
      relevant risk factors and attribute a relative weighting to each factor. Software
      may be helpful. The roles of the age high-risk productions, their life-style,
      modalities of therapeutic intervention, and economic implications are discussed.

PMID- 9772957
TI  - [Heart rate and mortality].
AB  - Is increased heart rate a marker or a risk factor of cardiovascular morbidity and
      mortality? Several studies, including the Framingham study, have reported an
      association. In a large-scale French study, conducted in the Centre
      d'Investigations Preventives et Cliniques of Paris, based on a cohort of 20,000
      male and female patients, heart rate was found to be a marker independent of the
      other risk factors and its increase was correlated with that of overall mortality
      in women, and cardiovascular and non-cardiovascular mortality in men. It remains
      to be seen whether pharmacological reduction of heart rate decreases mortality.

PMID- 9772959
TI  - [Heart rate and sympathetic risk].
AB  - A number of retrospective epidemiological and clinical arguments described in
      this article demonstrate that elevated heart rate (HR) is a predictive factor of
      cardiovascular risk due to activation of the sympathetic system which increases
      blood pressure and increases the risk of atherosclerosis and its complications.
      However, no epidemiological study has prospectively studied HR as the primary
      endpoint.

PMID- 9772958
TI  - [Heart rate: mechanical risk].
AB  - The artery is subject to tangential mechanical forces, involving heart rate and
      shearing forces. A mechanical theory of atherosclerosis explains the preferential
      development of plaques according to the distribution of these forces.
      Experimental data and an epidemiological article are in favour of the role of
      heart rate in cardiovascular complications. However, the benefit of therapeutic
      reduction of heart rate will probably be difficult to prove except in cases in
      which arterial lesions develop rapidly, as demonstrated in Marfan's disease.

PMID- 9772960
TI  - [Measurement of heart rate].
AB  - Like all laboratory parameters, measurement of heart rate must comply with
      certain theoretical conditions. In practice, it results from a compromises
      between the defined objectives, the material and the conditions of measurement.
      Effort are made to reproduce baseline conditions. The questions of the duration
      of measurement, it reproductibility, expression of the results, and the methods
      themselves are discussed. Standardization is required.

PMID- 9772961
TI  - [Factors of variation of heart rate].
AB  - Heart rate (HR), which participates in the short-term control of blood pressure
      and blood flow, depends on an intrinsic system and an extrinsic system via which
      the central nervous system processus and regulates the afferent stimuli of
      baroceptors and chemoreceptors. The situations responsible for short-term
      variations of HR include effort, the "white coat" effect, circadian rhythm, age,
      gender. The long-term maintenance of the HR level is dependent on nervous
      mechanisms, and haemodynamic and energetic conditions.

PMID- 9772962
TI  - [Heart rate and diabetes mellitus].
AB  - Diabetic neuropathy, particularly autonomic disorders, is early and frequent.
      When it affects the heart, it is also called cardiac autonomic neuropathy (CAN)
      and its clinical manifestations, especially increased heart rate, and subclinical
      manifestations are reported here, together with the techniques used to study this
      disease: Ewing's test, "Finapres", Holter ECG. Tachycardia, occurs early, is
      almost constant during diabetes and has a prognostic value.

PMID- 9772963
TI  - [Heart rate and lipids].
AB  - Heart rate (HR) appears to be an independent marker of cardiovascular risk, based
      on certain epidemiological data. Several studies have tried to establish a
      predictive cutt-off value. Many studies have observed the existence of a positive
      and independent correlation between HR and triglyycerides, VLDL, and a negative
      correlation between HR and HDL cholesterol. The recommended techniques for HR
      measurement, pathophysiological hypotheses, and clinical implications are
      discussed.

PMID- 9772964
TI  - [Modifications of heart rate and blood pressure during pregnancy].
AB  - The pathophysiology of pre-eclampsia, disease of the endothelium, placental
      ischaemia, and its consequences on blood pressure and heart rate variations are
      described. The methods of evaluation of heart rate and blood pressure during
      pregnancy, outpatient visit clinical measurement, self-measurement, ambulatory
      measurement, "Finapres", electrocardiogram and Holter ECG are reviewed; the
      practical implications of the nocturnal fall of vagal tone with tachycardia,
      demonstrated during pre-eclampsia, are discussed.

PMID- 9772965
TI  - [Heart rate: risk factor, risk marker].
AB  - When a correlation between an individual characteristic and the incidence of a
      disease is detected in epidemiology, this characteristic must satisfy four
      criteria before it can be considered to be a risk factor it must be strongly
      associated, universally associated regardless of the population, gender, race,
      associated independently of already recognized factors, especially age, and a
      cause-and-effect relationship must be demonstrated by a study influencing this
      characteristic. The first three criteria define the risk marker. Various examples
      are given, including that of heart rate and overall and cardiovascular morbidity
      and mortality.

PMID- 9772966
TI  - [Leiomyosarcoma of the heart and great vessels].
AB  - Leiomyosarcomas (LMS) of the heart are exceptional primary malignant tumours with
      a catastrophic prognosis and a mean survival measured in months. Extensive
      radical surgical resection clearly remains the most appropriate treatment. We
      report three cases observed over a 3-year period, consisting of an LMS of the
      inferior vena cava, an LMS of the pulmonary artery trunk and an LMS of the left
      atrium. The first case was treated by radical resection and reconstruction by
      autologous vein graft of the cavorenal junction, the second case was treated by
      extensive resection and prosthetic reconstruction of the pulmonary artery
      bifurcation and the third case was treated by a first radical resection of the
      left atrium, requiring total cardiectomy and orthotopic heart transplantation for
      local recurrence at the sixth month. The survical was significantly improved
      compared to other treatment options (chemotherapy, radiotherapy). The first
      patient is still alive without recurrence at two years; the second died 12.5
      months after the surgical procedure and the medium-term follow-up of the
      transplanted patient revealed cerebral and hepatic metastases nine months after
      transplantation. The authors review the literature concerning these extremely
      rare malignant tumours. Recent progress of diagnostic investigations, such as
      spiral CT with reconstruction, MRI, positron emission tomography (PET), are now
      able to establish the diagnosis more rapidly and therefore allow more radical
      surgical resection. This resection, possibly combined with venous reconstruction,
      must be associated with adjuvant therapies. Heart transplantation should be
      considered among the treatment options for leiomyosarcomas of the heart, in order
      to improve the poor prognosis of these lesions affections a young population.

PMID- 9772967
TI  - [Muscle bridge and myocardial ischemia. Study of 6 cases].
AB  - The authors analyse the clinical and therapeutic aspects of myocardial bridges in
      a series of 6 male patients between the ages of 41 and 61 years. In every cases,
      the presenting signs were ischaemic order: one myocardial infarction, three cases
      of unstable angina and two case of stable angina. On coronary angiography, these
      muscle bridges involved the left anterior descending artery in all cases. The
      causal relationships between muscle bridges and myocardial ischaemia are
      discussed. Among the various factors incriminated, spasm, tachycardia and
      thrombosis appear to play an important role. Depending on the case, treatment
      modalities consist of beta-blockers, platelet antiaggregants and calcium channel
      blockers. Surgical treatment is reserved for patients who remain symptomatic
      despite medical treatment.

PMID- 9772968
TI  - [Candida albicans myocarditis or endocarditis? Echocardiographic aspects].
AB  - The authors report the case of a patient presenting with atypical features of
      Candida albicans cardiac infection, with unusual infectious destructive lesions.
      While the initial hypothesis was that of aortic endocarditis, the clinical course
      and operative findings showed echocardiographic features of septal micro
      abscesses adjacent to the aortic orifice, which was devoid of any infectious
      lesions.

PMID- 9772970
TI  - [Hormone replacement therapy and prevention of postmenopausal cardiovascular
      diseases].
AB  - Hormone replacement therapy (HRT) prevents and delays the development of
      cardiovascular diseases affecting postmenopausal women, particularly coronary
      insufficiency. This favourable action has a multifactorial mechanism and
      concerns: the heart, as HRT improves diastolic filling; the arteries, especially
      the coronary arteries, which HRT dilates by increasing NO production and possibly
      via its antioxidant properties; carbohydrate and lipid metabolism, which are
      modified in a direction unfavourable to atheroma; haemostasis, because it
      decreases the risk of thrombosis and increases endogenous fibrinolysis. These
      properties are essentially due to oestrogens, but they persist with the addition
      of progestogens. They encourage the prescription of HRT for as long as possible,
      although the recommended duration currently remains unclear. With time, however,
      the slightly increased breast cancer risk demands at least annual review of
      treated women.

PMID- 9772971
TI  - [Cancer of the lower esophagus and the cardia].

PMID- 9772969
TI  - [Intra-aortic covered endoprosthesis].
AB  - Because of the risk and complications related to surgery of the aorta, the
      development of new, less invasive endovascular techniques has resulted in a
      certain enthusiasm for these new treatments on the part of physicians and
      industry. The insertion of aortic stents allows the treatment of almost one half
      of aneurysm of the infrarenal abdominal aorta and descending aorta. The results
      appear to demonstrate the medium-term reliability and efficacy of these new
      techniques with a lower morbidity-mortality rate than that of conventional
      surgery. However, preoperative and intraoperative imaging plays an essential role
      in the success of these new methods. Finally, although the medium-term results
      are encouraging, the long-term outcome of these new materials is unknown, which
      justifies close surveillance of these patients and prospective comparative
      studies.

PMID- 9772972
TI  - [Pretherapeutic evaluation in cancer of the cardia].

PMID- 9772976
TI  - [Adenocarcinoma of the Barrett esophagus. Apropos of 44 resected cases].

PMID- 9772974
TI  - [The value of extensive lymphadenectomy in cancer of the lower esophagus and
      cardia].
AB  - Between 1980 and 1997, 1194 patients with a malignant tumor of the lower
      esophagus have been observed and treated in our Institution. There were 555
      patients (46.5%) presenting with squamous-cell carcinoma, 101 (8.5%), with
      Barrett's adenocarcinoma and 538 (45%) with cardia adenocarcinoma. Most patient
      underwent a transthoracic esophagectomy with esophagogastroplasty; transhiatal
      approach was mainly reserved to high-risk patients. Over the past two years sixty
      three patients (42 with adenocarcinoma and 21 with squamous cell carcinoma)
      underwent enlarged mediastinal lymphadenectomy. Three patients (4.7%) died post
      operatively: one sepsis, in pulmonary embolism and one myocardial infarction.
      Four patients (6.3%) developed pulmonary complications: no patient had
      recuriential palsy. Pathologic exam revealed 1342 nodes (807 thoracic and 827
      abdominal). Twenty patients (31.7%) had mediastinal nodal metastases, of which 8
      in the upper mediastinum. Median follow-up was 19 months (2-36 months). Seven of
      the sixteen patients with recurrent disease (12 systemic, 3 mediastinal and 1
      anastomotic) died. The number of metastatic nodes increased with serial section
      and even more with immunohistochemical staining technique (from 11.7% to 13% to
      15.5%, respectively). Two patients were up-staged from M0 to M1 because of
      peripancreatic nodal micrometastases. We conclude that enlarged mediastinal
      lymphadenectomy allowed to detect upper mediastinal lymph node metastases in
      12.8% of patients without increasing post-operative complication rate. A longer
      follow-up is required to evaluate the impact on long term survival.

PMID- 9772975
TI  - [Surgical strategy of adenocarcinoma of the cardia].

PMID- 9772973
TI  - [Results of the surgical treatment of cancer of the cardia].
AB  - OBJECTIVES: In the curative treatment of the adenocarcinoma of the cardia (AC),
      the extent of the esogastrectomy and the need for lymph node dissection are still
      debated. The palliative treatment of AC is now currently non-surgical. The aim of
      this study was (a): to assess early results of palliative surgery; and (b) to
      evaluate the results of curative resection with reference to the influence of the
      extent of gastrectomy and lymph node dissection on early results and long-term
      survival. Methods. From 1979 to 1989, 179 patients (mean age = 60 +/- 12 years)
      with AC had 45 palliative resections (mean age = 56 +/- 15) and 134 curative
      resections (mean age = 61 +/- 12). Thirty-eight proximal subtotal esogastrectomy
      (PSOG) and 7 total esogastrectomy (TOG) were palliative; 72 PSOG and 62 TOG
      extended to the spleen were curative and associated with lymphadenectomy.
      RESULTS: The operative mortality rate was 8.9% regardless of the palliative or
      curative intent of resection. After palliative resection, the mortality rate was
      2.6% (1/38) after PSOG and 42.9% (3/7) after OGT = (p = 0.01); the median
      survival was 8 months. After curative resection, the mortality rate was 12.5%
      (9/72) after PSOG and 4.8% (3/62) after extended TOG (p = 0.2); actuarial 5-year
      survival rate was 42% after PSOG and 39% after extended TOG. CONCLUSIONS: These
      results suggests that: (a) palliative PSOG for AC can be performed with a low
      mortality; and (b) resection with extensive lymphadenectomy allows substantial
      survival regardless of the extent of gastrectomy.

PMID- 9772977
TI  - [Perspectives in the treatment of peritoneal carcinosis].

PMID- 9772978
TI  - [Surgical strategy for peritoneal carcinosis of ovarian origin].
AB  - Cancer of the ovary is usually discovered in an advanced stage after development
      of peritoneal carcinosis. Surgery is a fundamental element for diagnosis and
      treatment. Therapeutic strategy for cancer of the ovary discovered in an advanced
      stage includes first-line surgery and systematic postoperative chemotherapy. The
      essential prognostic factor is the quality of the initial surgical resection and
      the size of the residual tumoral tissue. Hysterectomy with adnexectomy,
      omentectomy, lumbo-ovarian and pelvic node dissection and extensive excision of
      visible carcinosis nodules, with if need digestive resection, are required for
      optimal tumor reduction. This aggressive surgery should be performed by well
      trained surgical teams.

PMID- 9772979
TI  - [Treatment of peritoneal carcinosis of colorectal origin].

PMID- 9772980
TI  - [Intraperitoneal chemo-hyperthermia with mitomycin C in cancer of the stomach
      with peritoneal carcinosis].
AB  - We report 42 cases of gastric cancer with peritoneal carcinosis treated with
      intraperitoneal chemohyperthermia. Intraperitoneal chemohyperthermia was achieved
      with a closed sterile circuit containing mitomycin C, 10 mg/l producing an input
      temperature varying from 46 to 49 degrees C for 90 minutes. There were three
      postoperative deaths: one pulmonary embolism at day 4, one multiple organ failure
      et day 4, and one septic shock at day 25 due to a colonic fistula. Two patients
      suffered complications: one opening of the duodenal stump requiring reoperation
      on day 5, and one prolonged postoperative ileus lasting to day 10. Of the 12
      patients with ascites, resorption was achieved in 8. In patients with early-stage
      peritoneal carcinosis (granulations less than 5 mm) survival at 1, 2 and 3 years
      was 90%, 61% and 41% respectively. For those with more extensive carcinosis,
      survival at 1 year was 10%. Five patients survived more than 30 months, three
      have survived to 34, 43 and 73 months. Intraperitoneal chemohyperthermia is a new
      treatment for carcinosis of gastric origin. These early results must be assessed
      further with larger controlled.

PMID- 9772981
TI  - [Early postoperative morbidity after hemorrhoidectomy using the Milligan-Morgan
      technic. A retrospective studies of 1,134 cases].
AB  - Milligan and Morgan's procedure is commonly used for the surgical management of
      haemorrhoids. The aim of our study was to evaluate short term postoperative
      morbidity. Between 1975 and 1990, 1,134 patients were operated on. Two patients
      died after operation. The most frequent complications were pain (71%) and urinary
      retention (16.4%). Hemorrhages (7.6%) resulting in a re-operation occurred in 1%
      of cases. Other complications were rare and always cured by a specific treatment
      (stenosis: 2.9%, anal fissure: 0.5%, abscess: 0.6%, fistula in ano: 1.2%). Two
      patients had anal incontinence partially improved by biofeedback. Hemorrhoidal
      was 2%. Short term postoperative morbidity is generally low after Milligan and
      Morgan hemorrhoidectomy, with careful supervision in a surgical department and
      repeated postoperative care.

PMID- 9772982
TI  - [Secreting retroperitoneal paraganglioma. Apropos of a case].
AB  - A case of secreting, asymptomatic retroperitoneal paraganglioma is presented.
      Paragangliomas are rare neuroendocrine tumors and the malignant behaviour, higher
      than pheochromocytomas, is based on metastases or local recurrence. The treatment
      is complete surgical excision. Radiotherapy and chemotherapy may be used for
      palliation of symptoms.

PMID- 9772983
TI  - [Adrenal cortex tumor. Apropos of a case].

PMID- 9772984
TI  - [Pre-peritoneal bisaccular umbilical and subcutaneous abscess after laparoscopic
      appendectomy].
AB  - Laparoscopic surgery has gained much interest since its advent the late eighties.
      A 36-year-old patient underwent laparoscopic appendicectomy via the
      transumbilical route. She was rehospitalized three times thereafter for
      subumblical pain. At day +48, an abscess was evacuated at the point of the
      umbilical trocar insertion. This hour-glass shaped abscess had a preperitoneal
      and subcutaneous localization, blocked by the epiploic reaction. The infection
      this patient developed is an unusual clinical finding as pain was localized at a
      distance. The umbilical site and the preperitoneal subcutaneous nature of the
      abscess are also unusual. This case emphasizes the gravity of post-operative
      abscess of the abdominal wall and the necessity for adequate prophylaxy.

PMID- 9772985
TI  - [The standards of care in laparoscopic surgery. The specific case of
      cholecystectomy].
AB  - Legal suits against visceral surgeons have increased since the advent of
      laparoscopic surgery. The duties of physicians have not however changed with the
      development of laparoscopic techniques. Since the decree promulgated in 1936,
      physicians have a legal commitment to provide the means required for patient
      care. This obligation has been recalled in different court judgements and in the
      new deontology code. In addition, jurisprudence tends more and more towards
      responsibility without risk. Laparoscopic cholecystectomy is not risk-free.
      Although morbidity and mortality have not risen with laparoscopic procedures, the
      types of complications encountered have changed. Reported accidents have become
      more frequent. The number of suits against surgeons has also increased. Surgeons
      must therefore be highly prudent and diligent. Precautions concerning personnel
      management, the choice of material and its upkeep. Special care must be given to
      the peroperative pneumoperitoneum and the use of monopolar electrocoagulation. A
      peroperative cholangiogram should be obtained. A careful operative report is very
      important. The surgeon must be able to justify his competence. Finally, the
      surgical community should publish more results concerning the rate of
      complications in order to establish reference material for experts.

PMID- 9772986
TI  - [The role of subtotal/total colectomy in the urgent treatment of obstructive
      cancer of the left colon].
AB  - PURPOSE: The aim of the study was to evaluate the results of management of
      acutely obstructed carcinoma of the left colon by emergency subtotal/total
      colectomy (STC) with immediate anastomosis without diversion. METHODS: STC was
      performed in 48 patients (mean age 72 years). Inclusion criteria were reasonable
      operative risk, resectable acutely obstructed carcinoma, massively-distended
      colon of dubious viability, signs of impending cecal perforation. RESULTS:
      Postoperative mortality was 6.2% (n = 3): 2 patients over 85 years of age died
      postoperatively as a result of cardiopulmonary complications: an 83 year-old
      female dies as a result of an anastomotic dehiscence. Morbidity was 12.4% (n = 6)
      including one fistula which recovered without surgery. There were 4 synchronous
      colon cancers. Six months after surgery, the mean daily stool frequency was 2
      after STC, and 3 after TC. CONCLUSION: Emergency STC achieves in one stage relief
      of bowel obstruction and tumor resection by encompassing a massively distended
      and fecal-loaded colon with ischemic lesions, ensures restoration of gut
      continuity via a "safe" anastomosis and removes occasional synchronous carcinoma.

PMID- 9772987
TI  - [The value of peroperative colonic lavage in urgent colonic surgery. Apropos of
      54 patients].
AB  - The effects of on-table colonic irrigation followed by primary large bowel
      resection and anastomosis for emergency left colonic disease were prospectively
      studied in 54 patients. PATIENTS AND METHODS: Eighteen patients had a
      diverticular sigmoiditis complicated by localized (8) or generalized (4)
      peritonitis, 6 presented a complete sigmoid obstruction. Thirty six patients had
      a left colonic occlusive (33) or perforated (3) cancer. Anterograde colonic
      irrigation was carried out with a mean volume of 7.7 l. All patients received a
      double or triple antibiotic combination. The anastomosis was handsewn in 33 cases
      and stapled (Knight-Griffen) in 21. Seven patients with severe peritonitis had a
      proximal transitory stoma which was closed within 4 months. RESULTS: Two patients
      (3.7%) died postoperatively, one for anastomotic dehiscence and the second for
      evisceration. We observed 7 cases of hypothermia (< 34 degrees C) during the
      irrigation. Six patients developed a sepsis of the surgical wound, 2 a septicemia
      and l an abscess in the right iliac fossa which was percutaneously drained. All
      complications had a favourable outcome. CONCLUSION: This study confirms that in
      selected cases a single stage surgery for colonic emergencies preceded by on
      table irrigation grants good results and is a safe and effective alternative to
      Hartmann's procedure.

PMID- 9772988
TI  - [2-stage surgery of neoplastic left colonic obstruction remains the safest
      procedure].
AB  - From January 1989 to December 1996, 56 consecutive patients underwent emergency
      surgery for occlusive cancer of the left colon. Excepting 12 patients whose
      symptomatology and radiographic presentation required medial laparotomy, the
      elective procedure was initial colostomy. There were 11 men and 33 women, mean
      age 76 years (range 50-97). Two patients in poor general status (ASA III) died
      during the postoperative period. Among the 42 survivors, the second procedure was
      not performed because of poor general status or disease progression in 6. Mean
      delay to the second procedure for resection was 11.5 days; during the same
      hospitalization for 32 out of 36 patients. The second procedure was segmentary
      colectomy in 34 cases and limited to exploratory laparatomy because of
      inextricable lesions in 2. Among the 34 re-operations with segmentary colectomy,
      the ostomy was removed in 28 at the second procedure and a third procedure was
      required in 6 cases. All the anastomoses in this series were sutured manually.
      Mortality for re-operation was nil. Pathology results (Duke's classification) in
      the 36 reoperated patients was: stage B = 3, stage C = 19, stage D = 14. In this
      series, operative mortality only concerned those patients whose condition was
      incompatible with selective surgery for colostomy. This risk cannot be lowered by
      any, other surgical approach. For the 34 resection-anastomosis elective
      operations, no major complications or deaths were observed. These results led us
      to recommend two stage surgery as routine strategy since survival of all those
      patients capable of sustaining an elective colostomy in an emergency setting can
      be assured.

PMID- 9772989
TI  - [The application of molecular technics in the management of colorectal cancer].
AB  - New technologies in molecular biology will allow the improvement of screening,
      diagnosis and prognosis of colorectal cancer patients. For example the
      determination of germline mutation in APC or in mismatch repair genes in patient
      with familial adenomatous polyposis or with HNPCC is now possible. The clinical
      surveillance can be restricted to the patients with these germline defects. More
      over the knowledge of somatic genetic alterations in colorectal cancer cells
      seems to be useful in the determination of prognosis of these patients or in
      order to predict the chemotherapy response.

PMID- 9772990
TI  - [Endoscopic monitoring after excision of colorectal cancer].
AB  - The aim of coloscopy after radical colorectal surgery for cancer is: to find
      another tumor or a local recurrence. The policy must be adapted. When the
      preoperative approach is inadequate, coloscopy must performed between 3 to 6
      months. After complete polypectomy, a coloscopic survey significantly reduces
      mortality and the incidence of colorectal cancer and has to be done at 3 years
      and then every 5 years. Data are not sufficient to establish a strategy for the
      local recurrence survey. The patients aged 75 and over, do not necessarily
      require repeated coloscopy.

PMID- 9772991
TI  - [The role of pancreatojejunostomy in the treatment of chronic pancreatitis].
AB  - From 1978 to 1995, 120 patients (105 males, 15 females, mean age: 46 years)
      underwent pancreatico jejunostomy (PJ) for chronic pancreatitis (CP). Alcohol
      abuse was presented in 105 cases (87.5%). PJ was the unique procedure in 67
      cases; it was associated with a biliary or a duodenal diversion in respectively
      38 cases and 5 cases. In ten cases, three diversions were performed.
      Postoperative mortality was 1.6% (n = 2), postoperative morbidity was 10% (n =
      12). Mean hospital stay was 16 days. Fifteen patients (13%) required a second
      operation some years subsequent to the PJ, due to the progress of the CP or
      alcohol abuse. In the late postoperative course 22 deaths occurred (18.5%), 8 of
      them were directly related to alcohol abuse. Mean follow-up was 7 years. Good and
      medium results for pain were evaluated to 92%, but the progression of exocrine or
      endocrine pancreatic insufficiency indicates that wirsung decompression was
      insufficient to stop the progressive sclerosis. In conclusion, PJ was our
      preferred surgical procedure in CP treatment, when the wirsung was dilated.

PMID- 9772992
TI  - [Results of laparoscopic cholecystectomy for acute cholecystitis in elderly
      patients].
AB  - OBJECTIVES: The aim of this retrospective study was to evaluate the feasibility
      and the morbidity of laparoscopic cholecystectomy for acute cholecystitis in
      elderly patients. METHODS: Among 891 consecutive patients who underwent
      cholecystectomy, 151 had acute cholecystitis. Fifty three patients of > or = 70
      years of age (group 1) were compared to 98 younger patients (group 2). Analysis
      was made in "intention to treat" so directly open cholecystectomies during the
      same period were also included. RESULTS: Elderly patients had a lower success
      rate of laparoscopic treatment (52.8% versus 70.4%; p < 0.05). This difference
      was due to higher rate of directly open cholecystectomy in the elderly (17%
      versus 2%). There was no difference between both groups in conversion rate to
      laparotomy (30.2% versus 26.5%). Surgical morbidity was 7.5% in group 1 and 4% in
      group 2 (NS). General complications were more frequent in the elderly (p < 0.05).
      Five patients in group 1 (9.4%) died of general complications of which 3 were
      operated on directly by open cholecystectomy. There was no mortality in group 2.
      CONCLUSION: Acute cholecystitis in the elderly remains a severe disease in which
      laparoscopic treatment is only possible in about fifty percent.

PMID- 9772994
TI  - [Computed tomography diagnosis of pancreatic abscess and its surgical drainage].
AB  - In a retrospective study of 40 patients with acute necrotizing pancreatitis, 16
      developed abscesses. The follow-up CT Scan and a radio-surgical cooperation
      permitted an early diagnosis of pancreatitis and time of surgical act. The 16
      abscesses had surgical drainage, 5 patients died.

PMID- 9772993
TI  - [Microbial overgrowth syndrome after gastrectomy. Recent diagnostic aspects].
AB  - Blind loop syndrome is the most common syndrome of bacterial overgrowth following
      gastrectomy. We report two cases with diarrhea, steatorrhea, exudative
      enteropathy and major nutritional deficiency. Diagnosis was based on the breath
      test and aspirate analysis. Surgery with restoration of the duodenal continuity
      was the treatment. Patients with contraindications for surgery should be given
      prolonged antibiotic therapy which should be repeated if symptoms reoccur.

PMID- 9772995
TI  - [Treatment of congenital dilatation of the bile ducts. Apropos of 3 cases].
AB  - Congenital dilatation of the bile duct is an uncommon lesion requiring surgical
      treatment. Complete excision of the diseased bile duct prevents development of
      carcinoma of the bile duct. We report three cases of congenital dilatation of the
      biliary three, each illustrating a particular aspect of the therapeutic strategy.
      One patient had an unusual anomaly of the pancreaticobiliary junction that
      required pancreaticoduodenectomy. Another patient developed carcinoma of the bile
      duct 15 years after an internal derivation of a choledochal cyst. The last
      patient had dilatations of the common and intrahepatic bile ducts associated with
      congenital hepatic fibrosis.

PMID- 9772996
TI  - [Intrathoracic retrotracheal goiter: excision through a cervical approach].
AB  - A case of retrotracheal goiter in the posterior mediastinum in a 53 year-old
      woman revealed by dyspnea is here described. A computed tomographic scan and
      magnetic resonance imaging specified the his extension from the lower flap of the
      thyroid, and its relationships in the mediastinum. It was removed through a
      cervicotomy only.

PMID- 9772997
TI  - [Coverage flaps for loss of substance of the scalp. Our experiences apropos of 42
      cases].
AB  - We report our experience with 42 coverage flaps for tissue loss involving the
      scalp. Malignant tumors of the scalp were the major cause of tissue loss. Repair
      modalites and outcome are reported. This series included 23 local flaps, one
      pediculated regional flap, and 18 free flaps associated with three cranioplasties
      and four dura mater plasties due to invasion of the subjacent tissues. We discuss
      therapeutic indications and insist on selection criteria which depend on etiology
      (localization, form depth), local factors (integrity of the pericranium and
      subjacent structures) and general factors (age, sex, physical and psychological
      status, socioprofessional context, patient expectations). In all cases, we opted
      for tissue repair which offers greater safety with minimum function and esthetic
      morbidity.

PMID- 9772998
TI  - [Splanchnicectomy using thoracoscopy].
AB  - A technique of thoracic splanchnicectomy under video thoracoscopic control is
      reported. This simple and non aggressive procedure is indicated for very painful
      forms of pancreatic cancer and for some cases of chronic pancreatitis. It should
      relieve pain for a longer period than splanchnic nerve injection or radiotherapy.

PMID- 9772999
TI  - [Primary muscular echinococcosis. Apropos of 2 cases].
AB  - We report 2 cases of primary muscular hydatosis of the thigh in a 30-year-woman
      and a 75-year-man. The clinical picture was a benign soft tissue tumor. The
      ultrasound and C.T. scan exams confirmed the diagnosis and showed precisely the
      intimacy of the lesion with the femoral vascular axe. Preoperative diagnosis of
      this affection is mandatory in order to prevent any rupture of the cyst so as to
      avoid anaphylactic shock and local recurrence. Percystectomy is the treatment of
      choice for this lesion.

PMID- 9773000
TI  - [False radiologic pneumoperitoneum. The value of emergency abdominal computed
      tomography].
AB  - We report 2 cases of false pneumoperitoneum. The diagnosis was suspected on an
      upright chest or abdominal plain films. The absence of clinical signs and
      symptoms of peritoneal irritation suggested a wrong radiological diagnosis.
      Emergency CT scan definitely eliminated a pneumoperitoneum and suggested the
      right diagnosis in both cases. This exam may play the decisive role in preventing
      needless emergency laparotomy.

PMID- 9773002
TI  - [Lymphatic, hepatic and osseous metastasis of a carotid chemodectoma. Apropos of
      a case].
AB  - A case of malignant carotid body tumor with nodal, hepatic and bone metastases is
      reported. Carotid body chemodectomas are slow-growing tumors which invade local
      structures. These tumors are usually benign but can occasionally produce local
      and distant metastases. Development of metastatic localizations is the only
      formal proof of malignancy as histology cannot distinguish between benign and
      malignant chemodectomas. Bilateral carotid arteriography gives the diagnosis.
      Surgery is the basis of treatment and should be performed early in the course to
      limit operative complications. Radiotherapy can be given as adjuvant treatment.

PMID- 9773001
TI  - [Digestive cancers and choroid metastasis. Diagnostic circumstances and
      prognostic value apropos of 2 cases].
AB  - We report two observations of malignant gastric and pancreatic tumors with
      choroid metastasis. Clinical course was rapidly and spontaneously unfavorable.

PMID- 9773003
TI  - [Patient information and obtaining informed consent in laparoscopic surgery].
AB  - Since the advent of laparoscopic surgery, the number of suits against surgeons
      has risen. One of the most frequent complaints is the lack of sufficient
      information. Physicians in France have a formal obligation to provide information
      in the contractual legal context established since 1936. This notion has been
      confirmed in several court cases. The requirement for patient informed consent
      has been confirmed by several decisions of the Appeals Court and is stated in the
      code of deontology. The value of classical oral information has been recently
      questioned in certain court cases. We analyse the current legal situation in
      France and try to define the content of information required in the case of
      laparoscopic surgery in addition to the way this information is provided and the
      means of obtaining informed consent. The information provided must be
      personalised. The patient must informed that laparoscopy remains a surgical
      operation. It is licit to warn the patient of predictable risks according to
      statistical probabilities, of the team's experience and of the patients own
      status including past history and psychological factors. A written statement may
      be prepared but must remain a document complementary to personalised oral
      information. The surgeon must obtain and assure good patient comprehension. The
      surgical community should publish risk rates in order for surgeons to have
      reliable references which can be used to define the notion of exceptional risk.

PMID- 9773004
TI  - [Symptomatic common bile duct lithiasis: endoscopic treatment or surgical
      treatment?].
AB  - Since 1974, endoscopic sphincterotomy (ES) has been considered by most
      practitioners as the gold standard for the treatment of symptomatic common bile
      duct lithiasis (CBDL). Results of the seven prospectives randomized controlled
      trials comparing ES to surgery in the treatment of CBDL, acute pancreatitis and
      angiocholitis excluded, demonstrated that: 1) the rate of feasibility of ES
      ranged from 90 to 100%; 2) the rate of residual stones after first extraction
      attempt ranged from 4 to 23% and after second extraction attempt from 6 to 25%.
      After surgery, rate of residual stone ranged from 2 to 14%; 3) major
      complications were more frequent after ES than after surgery; on the opposite,
      minor complications were more frequent after surgery than after ES; 4) immediate
      mortality was higher after ES than after surgery; 5) cost of ES with or without
      de principle cholecystectomy was higher than surgery. In conclusion ES should not
      be the first treatment of symptomatic CBDL.

PMID- 9773005
TI  - [Staging of exocrine pancreatic cancer].
AB  - The aim of this review is to report results of investigations used in the staging
      of pancreatic cancer and draw a practical approach in the treatment of this
      cancer. For the diagnosis of pancreatic mass and the diagnosis of malignancy,
      ultrasonography and helical-CT seem to be the best methods. In cases of non
      evident malignancy, diagnosis of pancreatic cancer can be done by endoscopic
      retrograde cholangiopancreatography and confirmed by transcutaneous biopsy, under
      CT locating. The diagnosis of vascular involvement is usually done by helical-CT,
      while endoscopic ultrasonography gives best results in the diagnosis of lymph
      node involvement. The diagnosis of hepatic and peritoneal metastasis can be
      difficult, specially in case of small peritoneal deposits, but accuracy of
      helical-CT remains high. Grading of these investigations depends on the situation
      after performing ultrasonography and CT scan. When a pancreatic resection seems
      to be possible, a surgical treatment can be directly proposed or preceding by
      endoscopic ultrasonography for lymph node diagnosis, and/or laparoscopy for
      detection of small peritoneal deposits.

PMID- 9773006
TI  - [Technique for right hepatectomy].

PMID- 9773007
TI  - [Internal knots in laparoscopy].

PMID- 9773008
TI  - [Antral exclusion in palliative surgery of cancer of the pancreas].

PMID- 9773009
TI  - [Surgical treatment of gastroesophageal reflux. Which technique to chose?].
AB  - Several procedures can be performed for gastroesophageal reflux disease. The aim
      of this review is to answer two main questions what are the validated procedures?
      should the procedures be tailored to patient? Surgical treatment is now based on
      fundoplications. Several controlled trials compared different types of
      fundoplications, the analysis of their results shows that the total and posterior
      fundoplications were equally effective at short-term. Total fundoplications were
      however more effective at long-term but with a higher morbidity. Technical
      variants include the ligation of short gastric vessels, the crura repair, the
      extend of the oesophageal overlapping by the partial fundoplication (180 degrees,
      270 degrees, or 300 degrees), and the dissection of the vagus nerves. The choice
      of a procedure should also take into account oesophageal manometry and possible
      associated diseases. Lower oesophageal sphincter pressure does not appear
      mandatory contrary to impaired oesophageal body motility which should
      contraindicate a total fundoplication. For oesophageal stricture, current
      agreement is to perform a total fundoplication together with an endoscopic
      dilatation when it is feasible.

PMID- 9773010
TI  - [Young woman of 22 years admitted for abdominal trauma].

PMID- 9773011
TI  - [Paper, Internet and video ( editorial)].

PMID- 9773012
TI  - [Therapeutic choices for cancer of the rectum: discussion and update of the
      consensus conference].
AB  - Three years after the consensus conference on the therapeutic options for rectal
      cancer, a recent literature review gave us some decision elements. Quality of the
      surgical resection appears to be the most important therapeutic factor in the
      prognosis of rectal cancer. Total mesorectal excision was followed by a
      significant decrease of locoregional recurrence rate for the tumor of the two
      lower thirds of rectum. In this way, it has been shown that pelvic nerves can be
      easily preserved. Which nerves are important for a good postoperative sexual
      activity remains however debated. Furthermore, whether the nerve sparing
      techniques influence the prognosis is also a matter of controversy. On the other
      hand, abdominoperineal resection is still indicated in most lower tumors to
      prevent local recurrences. Preoperative radiation therapy appears more effective
      than the postoperative one to decrease postoperative local recurrence rate after
      B2 (Astler-Coller) or T3 (TNM) tumors. At present, only one study showed that
      preoperative radiation therapy improved five-year survival. Combination of
      radiotherapy and chemotherapy improves also five-year survival, but this option
      leads to high toxicity. Thus the best adjuvent treatment remains to be defined.
      Awaiting for this, the good quality of surgical resection is mandatory.

PMID- 9773013
TI  - [Inguinal hernia treatment].
AB  - Efficacy of groin hernia repair is mainly evaluated by its recurrence rate. In
      the literature it depends on the type of surgery but also on the follow-up, which
      must last 5 years at least and has to be more than 90% complete. To acertain the
      clinical result, the patient must be examined by a surgeon. Among herniorraphies
      techniques, Shouldice procedure has the lowest recurrence rate. The Lichtenstein
      operation leads to less recurrence rate than McVay's, for mixt (direct and
      indirect) hernias. Post operative pain might be diminished after the former
      procedure. No randomized control trial has compared raphies and techniques
      involving a prosthesis, in groin hernia repair. Among laparoscopic techniques,
      the transabdominal and preperitoneal approaches have less recurrence rate than
      the entirely intra peritoneal one, which has been abandonned. Their recurrence
      rate is not different than recurrence rate of herniorraphies and techniques using
      a prosthesis. With them, post operative abdominal pain is diminished.
      Nevertheless no randomized control trial has demonstrated any superiority of
      laparoscopic techniques on the Shouldice procedure.

PMID- 9773014
TI  - [Tension and suture free repair of groin hernias using a large, bilateral
      prosthesis and by the pre-peritoneal way].

PMID- 9773015
TI  - [Ileo-anal reservoir technique].

PMID- 9773016
TI  - [Lateral colostomy technique using a subcutaneous rod].

PMID- 9773017
TI  - [Adult fecal incontinence due to anal sphincter lesions: which preoperative
      preparations? Which surgical solutions?].
AB  - Management of fecal incontinence due to anal sphincter lesions involves a good
      preoperative evaluation. This tends to confirm the incontinence, to search its
      mechanism, and to classify it according to the type of sphincter lesion owing to
      manometry, ultrasonography, and defecography. The surgical option is discussed
      after failure of medical treatment and biofeedback. The aim of surgery is to
      restore the incontinence and to maintain the exemption function. The surgical
      procedures include the sphincter repairs, the sphincter substitution, or even
      colostomy. Among the procedures of sphincter repairs, the direct repair is
      performed for obstetrical ruptures or postsurgical lesions of the anal sphincter,
      and the pelvic floor repairs are performed for fecal incontinence with intact but
      poorly functioning sphincter. Failures of these conservative methods lead the
      surgeons to develop new techniques for anal sphincter substitution. Dynamic
      graciloplasty and artificial sphincter (both under evaluation) constitute
      currently the promising alternatives to colostomy.

PMID- 9773018
TI  - [Woman of 26 years old admitted after a laparoscopic cholecystectomy].

PMID- 9773019
TI  - Dermatomyositis, polymyositis and inclusion body myositis: current concepts.

PMID- 9773020
TI  - [Clinical diagnostic criteria for multiple system atrophy].
AB  - What are the distinctive criteria for the diagnosis of multiple system atrophy?
      The combination of motor, dysautonomic, neuropsychological and eyes movements may
      help to distinguish, at a early stage, multiple system atrophy from other
      neurodegenerative diseases such as Parkinson's disease, progressive supranuclear
      palsy or corticobasal degeneration. Thus, these criteria are suitable both for
      clinical care and drug trials.

PMID- 9773021
TI  - [What does the Babinski sign have to offer 100 years after its description?].
AB  - One hundred years after its description, the Babinski sign remains a faithful and
      precise indicator of dysfunction in the pyramidal tract. Unlike a normal plantar
      reflex, which is a local reflex (S1), the Babinski sign is an integral part,
      though with its own specificity and thus value, of the defense reflectivity of
      the lower limbs. It should be triggered, preferably in the lateral region of the
      foot, by a non-painful stimulation. The characteristic response is a dorsal
      flexion of the greater toe by recruitment of the extensor hallucis. The
      pathological response is related to a dysfunction involving a precise fraction of
      the pyramidal tract (van Gijn. 1996), responsible for a monosynaptic stimulation
      of the extensor hallucis motor neurons, but also, via interneurons, for
      inhibition of the extensor hallucis. Its relationship with defense reflexes is
      certain (Walshe, etc.) put quite complex. We refer here to the "fanning" sign or
      Babinski "equivalents", plantar areflexia, peripheral "pseudo-Babinski",
      responses obtained by stimulating the plantar aspect of the foot in the newborn,
      and to global hyperflexion. We also discuss the role of the Lundberf dorsal
      reticulospinal tract.

PMID- 9773022
TI  - [Ataxic hemiparesis with cerebellar dysarthria due to an opercular lesion].
AB  - A 63 year-old-man, with an opercular infarct had a motor deficit with ataxic
      hemiparesis and cerebellar dysarthria. The motor deficit disappeared, but the
      cerebellar signs remained after three months. A voice instrumental analysis
      confirmed the cerebellar pattern of the dysarthria. CT and MRI showed the
      opercular lesion and the normality of the cerebellum and the pons. A volumic MRI
      analysis precised the localisation and the volume of the lesion. The oxygen
      consumption (CMRO2) was measured with PET and showed no cerebellar diaschisis. We
      propose that, in this case, the cerebellar dysarthria is the orofacial ataxic
      component of the hemiparesis. We suggest that it is related to disruption of the
      cortico-cerebellar tract, connecting the right orofacial frontal area of the
      primary motor cortex with the paravermal segment of the left cerebellar
      hemisphere.

PMID- 9773023
TI  - [Affective disorders due to the loss of mental self-activation. Comparison with
      athymhormia].
AB  - The affective state of the patients suffering from loss of psychic autoactivation
      (LPA) is preserved and is dampered as exhibited by a subtle examination, but
      depends on the same activation by the surrounding people as cognitive thought: it
      fades if the patient is not stimulated. This affectivity disorder cannot be
      responsible for LPA, but rather is part of its expression. The empty mind,
      characteristic of LPA, is not incompatible with the painful mood of the
      depression contrarily to our intuitive notion. In other words, the mood (or
      thymia) of patients with LPA is not neutral or null as suggested by the term
      "athymia". The term "anhormia" would describe rather well part but only a part of
      the disorder, the loss of drive. Furthermore, the term "self activation" has the
      advantage of highlighting, by contrast, the preserved heteroactivation, an
      essential part of the clinical picture. The heuristic value of this distinction
      is illustrated by the division it suggests between the so called "will" or
      "motivation" and of the circuitry supporting the two components. The term of LPA
      leads also to the description of a new state of conscious awareness, a
      consciousness devoid of any content.

PMID- 9773024
TI  - [Pure motor neuropathy after radiation therapy: 6 cases].
AB  - We report clinical and neurophysiological characteristics of six patients (five
      women and one man) presenting a pure motor bilateral asymmetric proximal and
      distal weakness in the setting of radiation therapy for Hodgkin's lymphoma in
      four cases, carcinoma of the uterus in one, and cancer of the ovary in one. Motor
      deficit, amyotrophy, cramps, fasciculations and tendinous areflexia were confined
      to the lower limbs in five patients and to the upper limbs in one. No sensory or
      sphincter disturbance was noted. The progression of the disease was slow with
      sometimes secondary stabilization. In some patients, CSF showed a slight increase
      in protein content with no cell. Blood and MRI medullary examination were normal.
      Delay between radiation therapy and onset of neurological symptoms range from 6
      to 24 years (mean 15). Neurophysiological findings suggest ventral roots proximal
      conduction blocks. We found an increase F-waves latency, a complete distal palsy
      contrasting with persistent muscle action potential after distal stimulation, in
      most of the patients; and an evidence of a conduction block between the erb point
      and the cervical roots using magnetic stimulation in the patient with upper limbs
      involvement. Mechanisms and sites of nerve radiation injury remains still
      unclear. These data could indicate, as it was already reported, a proximal damage
      involving predominantly the motor roots.

PMID- 9773025
TI  - [Hemicerebral atrophy and epilepsy in an adult].
AB  - We report the case of a 49 year-old man who presented a partial status
      epilepticus with left-sided clonic seizures after the occurrence of a left
      cerebral hematoma. The patient had left-side hemiplegia that progressively
      recovered in 3 months. Neuroimaging studies revealed a moderate cerebral atrophy
      on the right side and crossed cerebellar atrophy. Six years later, he had a
      partial status epilepticus with left hamiconvulsions leading to permanent left
      hemiplegia. The right cerebral and the left cerebellar atrophy observed one year
      later were significantly increased. Cerebral hemiatrophy associated with epilepsy
      in adulthood is exceptional. Our case suggests that the occurrence of partial
      status epilepticus, even during adulthood, may aggravate cerebral hemiatrophy
      formally silent.

PMID- 9773026
TI  - [Brown-Vialetto-Van Laere syndrome: a case with anti-ganglioside GM1 antibodies
      and literature review].
AB  - We report the case of a woman suffering from progressive bulbopontine paralysis
      in whose the first symptom, bilateral hypoacousia, began in childhood. This
      clinical picture is that of the Brown-Vialetto-Van Laere (BVVL) syndrome. Anti
      ganglioside GM1 antibodies were moderately elevated in this patient. Intravenous
      immunoglobulins produced little benefit. The main clinical characteristics of 29
      BVVL patients reported in literature are reviewed, and the pathological
      significance of anti-GM1 antibodies is discussed in the context of this disorder.

PMID- 9773028
TI  - [Rare neurological disorders and hypoglycemia. 3 cases].
AB  - We relate three cases of rare neurological disturbances associated with
      hypoglycemia (paraplegia, quadroplegia). Clinical symptoms completely disappeared
      within a few minutes after glucose administration. The pathogenesis of these
      types of deficit is not fully clarified, and a search of hypoglycemia should
      always be performed in these circumstances.

PMID- 9773027
TI  - [Pheochromocytoma revealed by cerebral hematomas. Significance of the abolition
      of a cutaneous abdominal reflex ipsilateral to the adrenal tumor].
AB  - Cerebro-vascular complications of pheochromocytoma are now rare. The case
      reported here is a 47-year-old woman who presented with two cerebral hematomas
      and a pheochromocytoma. Abolition of a cutaneous abdominal reflex abolition can
      help the clinician to locate the adrenal tumor side.

PMID- 9773029
TI  - [Vertical diplopia revealing posterior choroidal artery infarct].

PMID- 9773030
TI  - [Implementation of neurological expertise].

PMID- 9773031
TI  - [Spinal muscular atrophy: where are we in 1998?].

PMID- 9773032
TI  - [Wake disorders. I. Primary wake disorders].
AB  - Primary wake disorders encompass various conditions of excessive daytime
      sleepiness and/or increased nighttime sleep, of unknown origin beginning most
      often in adolescence and of chronic or recurrent natural history. The best known
      of these conditions is narcolepsy associating two major clinical features,
      irresistible episodes of sleep, sleep onset REM periods and an almost constant
      association with HLA DR2-DQ1. The prevalence of the condition is close to the one
      of multiple sclerosis but positive diagnosis requires most often over 10 years to
      be made. The treatment of excessive daytime sleepiness has recently benefited
      from a new non-amphetamine awakening compound, modafinil, active in 60 to 70 p.
      100 of the cases. The treatment of cataplexy still relies on antidepressants,
      tricyclics or selective serotonin reuptake blockers. Major advances in
      pathophysiology and pathogeny have been obtained through a natural model of the
      disease, canine narcolepsy. Pharmacological studies point to the importance of
      alpha-1 b adrenergic mechanisms in cataplexy, while dopaminergic systems seem
      more involved in excessive daytime sleepiness. As concerns genetics, the HLA
      DQB1*0602 gene predisposes to narcolepsy. In the canine model it is mirrored by
      an autosomal recessive gene showing a strong homology with the human
      immunoglobulin gene mu-switch. Familial studies have shown that besides typical
      phenotypes, attenuated forms of the condition characterized by isolated recurrent
      daytime naps and/or lapses into sleep do exist. In addition one or several other
      genes may be involved. Narcolepsy is multifactorial, including one or several
      genes as well as environmental factors. Idiopathic hypersomnia is noted for very
      long night sleep, difficulty waking up and more or less constant excessive
      daytime sleepiness. In contrast with narcolepsy sleep in not refreshing. There is
      no polysomnographic or immunogenetic special feature. Idiopathic hypersomnia is
      10 times less frequent than narcolepsy. It is often overdiagnosed due to
      insufficient knowledge of other causes of excessive daytime sleepiness such as
      the upper airway resistance syndrome. Modafinil is also of great value in the
      treatment of idiopathic hypersomnia. In the absence of an animal model,
      pathophysiology and pathogeny are still poorly understood. Even rarer is the
      Kleine-Levin syndrome which is easily distinguishable through its recurrent
      character and its tendency to progressively disappear. It mainly occurs in early
      adolescent males. Its main features are episodes of sleep of a week duration
      recurring at a several months' interval along with disturbances of alimentary and
      sexual behavior. There is no satisfactory treatment of hypersomniac episodes. On
      the other hand a prophylactic treatment with carbamazepine or lithium may be
      active. Pathophysiology remains unsettled in spite of some evidence of a
      hypothalamic functional disturbance.

PMID- 9773033
TI  - [Diseases transmitted by non-conventional agents ("prions"): nosology and
      diagnosis].
AB  - Transmissible non conventional agents are currently called "Prions". This is not
      a neutral terminology: the attractive Prion hypothesis (the infectious agent
      being a protein able to replicate in the absence of DNA or RNA) due to Stanley
      Prusiner is the prevalent one, and has shown to be heuristic, but has not been
      formally proven and does not easily explain all the data, unless modified and
      expanded. No simple account has been given for the very unusual physical,
      chemical, and biological properties of non conventional agents. These infectious
      agents are associated with degenerative diseases of the nervous system that are
      either the consequence of a genetic mutation or develop spontaneously in
      apparently normal individuals, and then can be transmitted to various susceptible
      hosts, including man. Thus, non conventional agents cannot be considered only as
      fascinating biological enigmas. They constitute a challenge for public health.
      The changing characteristics of prion-associated diseases has led to a renewing
      of their clinical and neuropathological diagnostic criteria. A brief survey of
      the nosology and neuropathology of prions diseases, with emphasis on new data and
      on difficulties, is provided. A simple classification based on the familial,
      sporadic or infectious variety of the disease is suggested. Familial diseases can
      be named according to the genetic disorder. Sporadic and infectious diseases can
      be classified following the main clinical symptoms and signs, and the presence or
      absence of amyloid plaques in the brain, until new tools (analysis of the
      glycosylation pattern of PrP, strain recognition) allow a more precise
      nomenclature. The new epidemiology of Prion disorders allowed by these new
      approaches relies on a full study of Prion diseases affected patients, which
      necessarily involves their genetic study, and the analysis of brain tissue. This,
      for practical and ethical reasons, is better achieved by autopsy.

PMID- 9773034
TI  - [A note on the epidemiology of Creutzfeldt-Jakob syndrome].
AB  - The annual incidence of sporadic Jakob-Creuzfeldt disease has been stable for the
      last 30 years. The new variant affecting young adults which appeared in the
      United Kingdom (20 cases) and France (1 case) in 1994 is due to the same
      infectious agent which causes bovine spongiform encephalopathy. Epidemiological
      data are still insufficient for a precise prediction of epidemics of the new
      variant mainly due to the duration of the incubation period of the disease.

PMID- 9773036
TI  - [Gerstmann-Straussler-Scheinker syndrome].
AB  - The Gerstmann-Straussler-Scheinker syndrome, is a disease transmitted by
      autosomal dominant inheritance characterized by nonsense mutations of the prion
      protein associated with specific neuropathological lesions-multicentric amyloid
      plaques labelled by antibodies directed against the prion protein. This
      restrictive definition justifies retaining the name of Gerstmann-Straussler
      Scheinder syndrome and excludes observations of hereditary prion diseases without
      multicentric amyloid plaques and sporadic forms with multicentric plaques. The
      main feature of these different observations is their polymorphous clinical
      presentation which varies not only between families with the same mutation but
      also with a given family. The underlying mechanisms of the phenotypic
      polymorphism remain uncertain.

PMID- 9773035
TI  - [Biology of non-conventional transmissible agents or prions].
AB  - Transmissible subacute spongiform encephalopathies (TSE) are a group of human and
      animal diseases which includes Creutzfeldt-Jakob disease, Gerstmann-Straussler
      Scheinker syndrome (GSS), Kuru, fatal familial insomnia (FFI), scrapie in sheep
      and goat, mink and feline transmissible encephalopathy, chronic wasting disease,
      and bovine spongiforme encephalopathy (BSE). TSE are transmissible among
      individuals of the same species and some of different species. These diseases
      stem from a specific category of agents that have biological and physiochemical
      characteristics unlike other micro-organisms; they are known as transmissible
      spongiform encephalopathy agent (TSA), prions, or virinos. So far, despite
      considerable progress made in the molecular biology toward the understanding of
      neurological injury, the nature of the TSA/prions remains unknown. TSE are
      characterised by the pathognomic accumulation, within the central nervous system
      of the infected individual, of a normal protein from the host organism, the PrP
      (prion protein). Differences between the PrP isolated from normal individuals
      (PrP-c) and PrP isolated from infected individuals (PrP-res) have been
      investigated. There are no differences in the sequence in amino acids, and the
      secondary structure seems identical, but since normal PrP is totally degraded by
      proteinase K pathological PrP resists to enzymatic digestion. One can therefore
      describe two PrP isoforms: a normal isoform, the PrP-c (c for cellular),
      sensitive to proteinase K and present in the normal individual and in the
      infected patients or animals: and a pathological isoform, the PrP-res, resistant
      to proteinase K and present in amount proportional to the infectivity in the
      brains of infected individuals. The presence of TSA/prions is detectable in the
      spleens of infected animals early after inoculation; it is then present in the
      CNS following a period not exceeding a half of the total length of the
      experimental disease. In the CNS, PrP-res is the origin of spongiosis and gliosis
      that are observed in infected individuals. A double causality, "infectious" and
      genetic, of these diseases can be derived from the various ideas currently
      accepted. Indeed the genetic basis of some familial forms has now been confirmed
      and transmissibility has been proven in natural situations such as the outbreak
      of CJD among children treated with extractive growth hormone and the recent surge
      of a new disease decimating British cattle, the bovine spongiform subacute
      encephalopathy, or mad cow disease. In TSE affected individuals, PrP has a key
      role in the incubation time and in the species barrier.

PMID- 9773037
TI  - [Cerebral hemosiderosis related to hereditary ceruloplasmin deficiency. Clinical
      familial case study].
AB  - A 59-year-old patient progressively developed dementia, hallucinations and facial
      dyskinesia. Brain T and T2-weighted MRI images showed low signal intensity on
      basal ganglia specially striatum, posterior thalamic and dentate nuclei. He had
      no evidence of ceruloplasmin and a high level of ferritin in the serum. Liver
      biopsy confirmed accumulation of iron in the cytoplasm of many hepatocytes.
      Similar clinical and biological signs were also observed in two brothers. All the
      three siblings were homozygous for a hereditary ceruloplasmin deficiency. This
      new clinico-pathological entity, first described in 1987, is different from
      Wilson's disease, Hallervorden-Spatz's disease and idiopathic hemochromatosis and
      linked to a mutation of the ceruloplasmin gene located on chromosome 3.

PMID- 9773038
TI  - [Extrapontine myelinolysis: treatment with TRH].
AB  - Central pontine and extra-pontine myelinolysis are a well known complication of
      hyponatremia. Other causes may be present. We report a case of head injury in a
      13 year-old girl, who recovered well after surgery for extra-dural hematoma, but
      presented endocrinological disorders with hyperglycemia followed by a severe
      hyponatremia. Despite the correction of these metabolic disorders, the patient
      became comatose, and MRI, on T2 weighted image, showed hyperintense signals in
      the basal ganglia consistent with extra-pontine myelinolysis. The patient's state
      remained unchanged for six weeks. Since S. Konno and H. Wakui published cases of
      myelinolysis who dramatically improved after TRH treatment, the patient was given
      0.6 mg i.v daily of TRH for six weeks. Improvement began within a few days, and
      continued until complete recovery.

PMID- 9773039
TI  - [Intramedullary metastases of bronchogenic carcinoma. Two cases].
AB  - Intramedullary metastases are uncommon. We report two cases in patients with
      small cell bronchogenic cancer. The clinical diagnosis was supported by T1
      magnetic resonance imaging after gadolinium injection. A unique medullary
      metastasis associated with other metastatic localizations was observed in the
      first patient and multiple intramedullary metastases alone in the second. These
      secondary intramedullary localizations were highly sensitive to chemotherapy
      after the first monthly cure in the first patient and after the third in the
      second patient. We emphasize the importance of chemotherapy in such cases,
      usually associated with focal radiotherapy.

PMID- 9773040
TI  - [Nervous system borreliosis with pseudo-lymphoma cells in cerebrospinal fluid].
AB  - We report the case of a 44-year-old woman, who experienced acute back pains, leg
      paraesthesia, and diplopia. Analysis of the cerebrospinal fluid revealed, in
      addition to increased protein and decreased glucose levels, an elevated number of
      large atypical cells, resembling lymphoma cells. Magnetic resonance imaging of
      the brain and spine was normal. High levels of antibodies against Borrelia
      burgdorferi were found in both serum and cerebrospinal fluid. The patient
      completely recovered with ceftriaxone therapy.

PMID- 9773041
TI  - [Epidural and intramedullary abscess of acute onset].

PMID- 9773043
TI  - [Sclerotic plaques and vaccination against hepatitis B].

PMID- 9773042
TI  - [Cranial nerve injuries during multifocal neuropathies with persistent conduction
      blocks].

PMID- 9773044
TI  - [Cytokines and peripheral neuropathies].
AB  - Cytokines are polypeptides produced by various cells, with key-roles in
      regulation of immune response, inflammation and hematopoiesis. Cytokine-producing
      cells in peripheral nerve include resident and recruited macrophages,
      lymphocytes, and likely mastocytes, Schwann cells, and probably neurons.
      Cytokines are instrumental in pathogenesis of peripheral neuropathies during
      nerve lesions and tissue repair. Tumor necrosis factor-alpha (TNF-alpha)
      injection into nerve induces Wallerian degeneration. In contrast, interleukin-1
      (IL-1) promotes detersion by scavenger macrophages, and increased synthesis of
      neurotrophic factor (nerve growth factor--NGF--and leukemia inhibitory factor-
      LIF). Neurotrophic cytokines IL-6, LIF and transforming growth factor-beta 1 (TGF
      beta 1) are overexpressed in nerve after experimental axotomy and promote axonal
      growth until axon/Schwann cell contact. In the course of inflammatory
      demyelinating neuropathies, proinflammatory cytokines induce vascular
      permeability and breakdown of blood nerve barrier (TNF-alpha, vascular
      endothelial growth factor/vascular permeability factor--VEGF/VPF), favor
      leukocyte transmigration into nerve, induce activation and proliferation of
      lymphocytes (IL-1, IL-2) and macrophages (gamma-interferon--IFN-gamma), and have
      a direct myelinotoxic activity (TNF-alpha and TNF-beta). In addition, the
      inflammatory process is likely favored by downregulation of the anti-inflammatory
      cytokine TGF-beta 1.

PMID- 9773045
TI  - [Clinical diagnosis of frontotemporal dementia].
AB  - Frontotemporal dementia (FTD) is poorly recognized clinically. Of the 1,517
      patients examined at the Lille Outpatients Memory Clinic data bank (1991-1995),
      74 fulfilled the criteria of the Lund and Manchester groups for FTD. They
      accounted for 5 p, 100 of all patients, 1 for 10 probable or possible Alzheimer's
      disease. Mean patient age was 63 years, duration of the disease was 5 years, mean
      Mini Mental State score was 23; 45 p. 100 belonged to the active population.
      Behavioral disorders occurred before the cognitive decline and remained the major
      feature. All patients had at least 3 of the following symptoms: self-control
      impairment, affective disorder, loss of interest and self-neglect. Memory
      impairment consisted of correct encoding and impaired retrieval processes,
      without major storage impairment. No patients had spatial disorientation.
      Language was usually reduced, EEG was normal. Two diagnoses were confirmed by
      autopsy: both consisted of aspecific frontal and temporal degeneration, 41 p. 100
      of the patients were referred by a general practitioner, 30 p. 100 by a
      psychiatrist, 16 p. 100 by a neurologist, 2 p. 100 by other specialists, and 11
      p. 100 following the advice of their relatives. FTD had never been suspected.
      Alzheimer's disease or non specified degenerative dementia was suspected in 2/3
      of patients and a psychiatric disorder in 1/3. With the advent of novel
      pharmacological agents for the treatment of dementing disorders and for research
      purposes, the identification and accurate differentiation of FTD from Alzheimer's
      disease and psychiatric disorder is essential. Therefore, the role of
      multidisciplinary memory clinic is crucial to differentiate FTD from other
      degenerative dementias.

PMID- 9773046
TI  - [Study of cortical atrophy with magnetic resonance imaging in corticobasal
      degeneration].
AB  - Corticobasal degeneration (C.B.D.) is a neurodegenerative disorder characterized
      mainly by an asymmetrical a kineto-rigid syndrome associated with fronto-parietal
      cortical signs, particularly apraxia. Conventional imaging even magnetic
      resonance imaging (M.R.I.) has often been considered as poorly contributive for
      the diagnosis of C.B.D. We retrospectively studied routinely performed M.R.I.
      scans of 15 patients presenting a clinical and metabolic (P.E.T/S.P.E.C.T.)
      syndrome characteristic of probable C.B.D. M.R.I. scans were assessed by 3
      investigators, not aware of the clinically most affected side, taking into
      account M.R.I. technical parameters. We quantified, on each side, the cortical
      atrophy (frontal, parietal and temporal) and the white matter changes, by using
      the semi-quantified method of Victoroff et al. (1994). Abnormalities were
      considered if observed by at least 2 of the 3 investigators. Abnormalities were
      then correlated with the side initially and most severely affected. The most
      contributive findings were the asymmetric parietal atrophy (clinically correlated
      in 93 p. 100 of cases), asymmetric frontal atrophy (clinically correlated in 60
      p. 100) and asymmetric dilatation of the lateral ventricles (clinically
      correlated in 60 p. 100). 80 p. 100 of affected subjects displayed at least 2 of
      these M.R.I. abnormalities. These results are in accordance with the metabolic
      and pathologic features of C.B.D. This study demonstrates that M.R.I. evaluation
      of the cortical atrophy asymmetry may contribute to the diagnosis of C.B.D.

PMID- 9773047
TI  - [Autosomal dominant nocturnal frontal lobe epilepsy].
AB  - Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a recently
      identified seizure disorder. The disease maps to the long arm of chromosome 20
      and may be related in some families to a missense mutation in the neuronal
      nicotinic acetylcholine receptor alpha 4 subunit. We describe one of the first
      European family with ADNFLE, including five affected individuals spanning four
      generations. In the most severely affected subject, the onset was during the
      second month of life and persisted through adult life. Seizures were very
      frequent during infancy, although long-term evolution was relatively benign.
      Ictal video-EEG studies showed that attacks occurred in clusters during sleep and
      were partial seizures that were consistent with a frontal origin. Neuro-imaging
      was normal. Carbamazepine had a dramatic effectiveness. Although recognition of
      this syndrome is important for appropriate therapy and genetic counselling,
      underestimation of cases is likely: the disease was in our family perceived like
      a hereditary curse, and subsequently concealed, including to medical attention.
      Relationships with other partial familial epilepsies and with idiopathic benign
      partial epilepsies of childhood are discussed.

PMID- 9773048
TI  - [Eosinophilic meningitis due to Angiostrongylus cantonensis].
AB  - Angiostrongylus cantonensis is the most common etiological agent of eosinophilic
      meningitis. Adults are harbored in the pulmonary arteries of rats. Larvae develop
      within various natural (mollusks) and paratenic (snails...) hosts. After
      ingestion, larvae reach the human central nervous system where they cannot
      complete their life cycle. This zoonosis is usually seen in Southeast Asia and
      South Pacific islands. Nevertheless, a few imported cases have been reported in
      Western countries, possible because of the incubation delay. Mild meningeal
      irritation signs, paresthesia, cranial nerve abnormalities (i.e: II, III, VI,
      VII) are the most usual by encountered signs. Severe cases with brain involvement
      have been reported. In endemic areas, typical clinical signs associated with
      C.S.F. eosinophilic pleocytosis allow the diagnosis but Elisa test may be useful.
      Prognosis is always excellent even if headache and malaise may last a few weeks.
      No antihelminthic agent is efficient against Angiostrongylus cantonensis.
      Prophylaxia by public health counselling program is fruitful.

PMID- 9773049
TI  - [Case of superficial hemosiderosis of the central nervous system treated with
      trientine].
AB  - A 58-year-old woman, with recurrent headaches, exhibited cerebellar alaxic gait,
      anosmia, deafness and a pyramidal syndrome, with a progressive onset. In
      cerebrospinal fluid there was erythrocytes and siderophages. MRI on T2-weighted
      images revealed a marginal hypo-intensity, leading to the diagnostic of
      superficial siderosis of the central nervous system. None haemorragic lesion was
      found. The patient was given Trientine. Unfortunately she worsened on later
      examinations.

PMID- 9773050
TI  - [Germinal tumor metastases. Case report].
AB  - Germinoma is the most frequent type of intracranial germ-cell tumor initial
      presentation is usually acute intracranial hypertension. MRI investigations are
      non-specific. Most of the time, only stereotactic surgery is performed before
      treatment. Metastases are rare but germ cells can disseminate both by
      infiltration and via ventricular and subarachnoid pathways. Abdominal and pelvic
      metastases occur in 10 p. 100 of patients who have received ventriculosomatic
      shunting. Since germinoma is well known to be a very radiosensitive tumor,
      patients are usually given radiation therapy. Chemotherapy seems to be an
      interesting alternative treatment.

PMID- 9773051
TI  - [Bradycardia: an unrecognized complication of some epileptic crises].
AB  - A 36-year-old man, treated for epilepsy since early childhood, was hospitalized
      for nocturnal paroxysmal disorders. The EEG-EKG-video monitoring revealed complex
      partial seizures with bradycardia secondary to a sino-auricular block. The
      occurrence of autonomic disturbances during seizures is well known, mostly
      described in temporal epilepsy. Ictal bradycardia, with asystole, has been
      unfrequently reported, while tachycardia appears more common. A systematic
      investigation of cardiac data synchronized with EEG recordings, especially in
      case of aspecific fainting, could give a more accurate diagnosis and treatment,
      and so reducing sudden unexplained death in epileptic patients.

PMID- 9773053
TI  - (Facial palsy relevant to HIV seropositivity)

PMID- 9773052
TI  - [Benign intracranial hypertension and chronic hypervitaminosis A].
AB  - We report a case of benign intracranial hypertension due to chronic A
      hypervitaminosis and a review of literature with 30 cases in adults and
      adolescents. The most prominent clinical features are: predominance of young
      women with normal weight and cured for acne; benign intracranial hypertension
      without other symptoms in half of cases; wide difference of daily doses and time
      of continuous intake. Prognosis for vitamin A intoxication is good, when intake
      of vitamin is discontinued. We reviewed five cases of benign intracranial
      hypertension due to retinoic acid. The mechanism of vitamin A neurotoxicity is
      still unknown.

PMID- 9773055
TI  - [Current status of mitochondrial diseases].

PMID- 9773054
TI  - [Pneumosinus dilatans: a little-known diagnostic tool].

PMID- 9773056
TI  - [Pointing and its object: towards the neuropsychology of objectivation].
AB  - We describe a disorder similar to body-image agnosia or autotopagnosia
      characterized by the inability to designate targets situated outside the body.
      This disorder, which we have termed allotopagnosia, occurs exclusively in
      subjects with a lesion involving the posterior region of the left parietal lobe.
      The most common manifestation is the designation of parts of the body of another
      person as being part of the patient's own body (heterotopagnosia with self
      designation). This disorder cannot be explained by aphasia, apraxia, or
      visuomotor dysfunction nor by an inability to identify parts of the body as self.
      Patient's expression of the confusion between their own body with that of others
      and the gestures they use to designate indicate a relationship with reality (non
      self and target) confined to the human species. The disorder appears in children
      at the same time as language acquisition. This suggests the hypothesis that
      allotopagnosia results from a deficit or dysfunction of the left parietal lobe
      where outside elements are attributed to situations and identities independent of
      self.

PMID- 9773057
TI  - [Vascular Parkinson syndromes: a controversial concept].
AB  - The concept of arteriosclerotic parkinsonism has created some confusion due to
      the absence of a precise definition of the parkinsonian syndrome and to a
      prolonged absence of knowledge concerning the topography of the lesions in
      "idiopathic" Parkinson's disease as well as the anatomic relations of the basal
      nuclei. Although certain authors at the beginning of the century suggested that
      Parkinson's disease could have a vascular origin, an opposition rapidly developed
      between Parkinson's disease and arteriosclerotic parkinsonism, largely based on
      the work by Cricthley (1929). The concept of arteriosclerotic parkinsonism is a
      quite ambiguous notion, but was generally accepted up to the sixties before
      severe criticisms were made when the anatomo-clinical characteristics of
      Parkinson's disease were identified. Recent work has again suggested that
      parkinsonism can be of vascular origin but the observations reported show a
      heterogeneous collection of lesions with different localizations, clinical
      expression and clinical courses. Clinically, two rare circumstances can be
      identified (vascular parkinsonism similar to Parkinson's disease and unilateral
      vascular parkinsonism due to contralateral lesions) and inversely much more
      frequent "atypical" parkinsonism syndromes. These differ from Parkinson's disease
      by their parkinsonism symptomatology (no resting tremor, predominance of gait
      disorders), the presence of associated neurological signs and lower sensitivity
      to levodopa. The attribution of the parkinsonism disorders to vascular lesions
      identified at imaging is often quite hazardous, but a few anatomo-clinical
      observations have confirmed that vascular parkinsonism does exist. The
      heterogeneous nature of the observations hinders the development of diagnostic
      criteria.

PMID- 9773058
TI  - [Epilepsy and psychiatric disorders: epidemiological data].
AB  - Data about psychiatric disorders associated with epilepsy as well as their risk
      factors are heterogeneous. The overall prevalence of psychiatric disturbances in
      epileptic patients can be estimated between 20 and 30 per cent. It is the highest
      in pharmocoresistant cases seen in specialized centers. Psychotic disorders,
      depression, and suicide are the three most common among interictal disturbances.
      Psychoses affect 2 to 9 per cent of patients and are more frequent in cases with
      aura or altered consciousness, such as in complex partial seizures and absences.
      They correlate positively with the multiplicity of seizures but often inversely
      with their frequency. Temporal lobe epilepsy is associated with schizo phrenic
      like and paranoid types of psychosis, but frontal lobe epilepsy is also common. A
      putative association with predominant left or bilateral EEG abnormalities in
      cases with partial epilepsy remains to be confirmed, as well as the frequency of
      underlying structural lesions. Depressive disorders affect 20 to 60 per cent of
      patients. While their occurrence with partial complex seizures and left
      hemisphere foci is common, the role of temporal lobe involvement still appears
      controversial. Depression prevails in cases with seizures that occasionally,
      albeit rarely, secondarily generalize and correlates with the duration of the
      disease, intractable seizures, and polypharmacy. A genetic factor is likely to
      play a role. Suicides rates are increased, encountered in 0.2-0.5 per cent of
      patients and causing deaths in 3-7 per cent of them. The overall risk might be
      the highest during the first years after diagnosis of epilepsy, as well as in
      patients with temporal lobe foci, depression, or psychosis. Great variability and
      discordance in results show the major difficulties encountered in epidemiologic
      studies. Most of these problems relate to the classification of epileptic
      disorders as well as that of psychiatric disorders, the variability in the
      methods and measures which are used, and frequent bias in the selection of
      patients. We review here data about the frequency of major psychiatric disorders
      in epileptic patients or the frequency of epileptic disorders in psychiatric
      patients, and also possible risk factors related to the epileptic disease and its
      evolution.

PMID- 9773059
TI  - [Auditory perception disorders due to bilateral cortical lesions. An
      electrophysiology study].
AB  - A 78-year-old right handed man with a past history of atrial fibrillation
      developed in November 1994, a slight right hemiparesis with aphasia which cleared
      over one month. Head CT scan showed a left middle cerebral artery infarct
      involving the posterior part of the temporal lobe. In September 1995, a second
      stroke occurred. Head CT scan revealed a recent right middle cerebral artery
      infarct within the posterior part of temporal cortex. Auditory agnosia was
      diagnosed. Auditory evoked potentials recording showed bilateral dysfunction of
      central auditory pathways mainly over the right hemisphere. Clinical data and
      evoked potentials suggest that auditory agnosia might be related to the right
      temporal lobe damage. This later is involved in linguistic processes as suggested
      by positron emission tomography studies.

PMID- 9773060
TI  - ["Primary" orthostatic tremor. 10 clinical electrophysiologic observations].
AB  - Orthostatic tremor is an unusual kind of potentially disabiling tremor appearing
      immediately when standing. Clinical examination is normal in primary form except
      for wide base standing and unsteadiness which disappear when walking. Arm tremor
      resembling essential tremor is found present in one third of cases.
      Electrophysiological exploration is necessary for diagnosis and shows a regular
      rapid tremor (frequency around 16 Hz). We present 10 new cases, 3 men and 7
      women, 37 to 74 years old. Unsteadiness when standing was the predominant
      complaint in 9 cases, the other first described pains in the lower limbs. All had
      visible or palpable tremor predominant in thighs. Four patients had postural arm
      tremor, one had neurogen syndrome in the lower limbs corresponding to toxic
      polyneuropathy which developed after tremor. Electromyographic study found high
      frequency (13-17.3 Hz) rhythmic discharge in weight-bearing muscles. Orthostatic
      tremor cannot be considered as a clinical variant of postural essential tremor.
      Its pathophysiology is unknown but the efficacy of clonazepam, primidone or
      barbiturates suggests the impairment of the gabaergic system.

PMID- 9773061
TI  - [Thyrotoxic neuromyopathies].
AB  - Chronic thyreotoxic neuromyopathy was observed in four patients. The first two
      cases were observed in a 43-year-old woman and a 60-year-old man. In the man,
      muscle disorders were the first manifestation and in the woman they were preceded
      by Graves' hyperthyroidism. Muscle signs were seen as functional impotency with
      amyotrophy of the girdle which was major in the man and minor in the woman. In a
      third case, a pyramidal syndrome was associated with polyneuropathy in a 28-year
      old man. Laboratory tests showed hyperthyroidism, neurological signs regressed
      with antithyroid drug therapy. A fourth case presented as thyrotoxic hypokaliemic
      periodic palsy in a 37-year-old man who had loss 12 kg over a two month period
      after a psychological stress. This man then experienced two acute episodes of
      hypokaliemia and hypotonic tetraplegia. These signs were linked to Graves'
      hyperthyroidism. Clinical course was good under carbimazole and then radioactive
      iodine. These four cases illustrate the reality of thyrotoxic neuromyopathies in
      black Africans.

PMID- 9773062
TI  - [Diagnostic dyspraxia and frontal syndrome].
AB  - A 27-year-old ambidexter woman experienced a clinical and psychometric frontal
      syndrome associated with a partial callosal syndrome following transcallosal
      surgery for an intraventricular neurocytoma. She also complained of difficulties
      with her left hand which realized a particular form of diagnostic dyspraxia:
      there were specific features of an isolated dysfunction of the control of the
      realization of a program.

PMID- 9773063
TI  - [Friedreich's ataxia and hereditary vitamin E deficiency. Case study].
AB  - A 24-year-old patient, born from consanguineous parents, consulted for cerebellar
      syndrome, ataxia, loss of proprioception, bilateral Babinski sign and lower limbs
      areflexia. No mutation on Friedreich's ataxia gene was found. Plasmatic vitamin E
      level was extremely low. Point mutation on gene coding for alpha-tocopherol
      transfer protein (alpha-TTP) confirmed the diagnosis of familial isolated vitamin
      E deficiency (AVED). Vitamin E therapy restored normal serum levels and
      neurological symptoms were stabilized.

PMID- 9773064
TI  - [Orthostatic hypotension revealing vitamin B12 deficiency].
AB  - Neurological manifestations of cobalamin deficiency are well known and various.
      We describe an uncommon clinical setting where major orthostatic hypotension was
      the primary symptom. Recovery was rapidly and completely stabilized with
      parenteral cobalamin substitution. There was no clinical or electrophysiological
      signs of neuropathic disorder. This entity is rare but few cases are described in
      literature. All of them were reversible with vitamin substitution treatment.

PMID- 9773065
TI  - [Lead intoxication and amyotrophic lateral sclerosis].
AB  - A seventy-six-year-old patient developed a bulbar form of amyotrophic lateral
      sclerosis, after chronic lead intoxication from drinking water. Treatment with
      2,3 dimercaptosuccinic acid was administered for six months and had no effect on
      clinical course. We discuss the imputability of lead as a possible etiological
      factor.

PMID- 9773066
TI  - Intracranial neuroma of the hypoglossal nerve: diagnosis and management. Case
      report and review of the literature.

PMID- 9773067
TI  - [With regard to a "blood-patch" in post-lumbar puncture syndrome].

PMID- 9773068
TI  - [Bilateral facial paralysis and deafness in a 47-year-old man].

PMID- 9773069
TI  - [Functional imaging of human muscle].
AB  - Medical imaging is now giving access not only to anatomy but also to functions of
      organs in the human body. Functional imaging may yield a direct appreciation of
      the function of a given organ, as is the case when measuring ejection fraction of
      heart with SPECT. Alternately the approach is indirect. This is the case of
      cerebral functional imaging, either with PET or NMR, where the perfusion increase
      induced by neuronal activity is detected. Recent developments of NMR, combining
      imaging and spectroscopy, allow now to detect modification of physiological
      parameters induced by muscular activity. Indirect detection of muscle activity is
      very rich in information alternately requiring invasive techniques. Water shifts
      resulting from intense exercise are detected either from muscle volume increase
      or water signal modifications, using simple NMR sequences. Then it is easy to
      identify which muscle is involved in a given protocol. These water shifts,
      studied in various muscles and several types of exercise protocols, reflect the
      perfusion increase induced by exercise, and the contribution of metabolic
      products such as lactate. In some patients with metabolic myopathies a decreased
      adaptation of perfusion has been detected. Perfusion measurements, previously
      performed by using venous occlusion plethysmography or radioactive tracers, now
      benefit from recently developed MR techniques. Oxygenation of muscle may be
      measured either by spectroscopy of myoglobin, allowing a time resolution of 1
      second, or by spectroscopic imaging allowing a spatial resolution of 1-2 cm in a
      few minutes. Muscle temperature may be non invasively monitored by diffusion
      weighted MR. Direct detection of muscle activity is useful only in those muscles
      that cannot be directly observed. Ultrafast MR imaging may be used to study vocal
      cords or oculomotor muscles. More interesting is the measurement of
      contractility, either in myocardium or skeletal muscle, allowed by MR with spin
      tagging. Another contribution of MR to muscle studies is the possibility to
      quantify muscle cross section and muscle volume, in order to normalize strength
      or metabolism measurements. Sequences using T1 or T2 differences between muscular
      and adipose tissue allow to quantify the true muscular volume in patients with
      neuromuscular disorders. Protocols combining several of these parameters by
      interleaved NMR measurements of perfusion, phosphorylated metabolites, lactate,
      myoglobin, now open the way to many comprehensive non-invasive pathophysiological
      studies.

PMID- 9773070
TI  - [Lesions of ponto-cerebellar and olivo-cerebellar afferents demonstrated by
      neurophysiologic analysis].
AB  - We describe a 52-year-old woman presenting a 2-year history of limb clumsiness
      and gait difficulties, characterized by progressive worsening. Neurological
      examination revealed cerebellar intention tremor, cerebellar dysmetria of all 4
      limbs and ataxic gait. However, brain MRI was normal. Analysis of fast wrist
      flexion movements demonstrated hypometric movements, with decreased intensities
      of agonist EMG activities and increased durations of antagonist EMG activities.
      Such EMG abnormalities have been demonstrated in patients presenting lesions of
      the middle cerebellar peduncle, affecting the crossed cerebellopontine
      projections. Moreover, adaptation motor learning during a pinch task (isometric
      force) showed a severe inability to adapt motor programming, indicating a
      disruption of cerebellolivary and cerebellopontine afferent systems. We suggest
      that our patient presented an exceptional brainstem syndrome involving the
      function of cerebellar inflow tracts. Such electrophysiological findings are not
      encountered in patients presenting a cerebellar cortical degeneration or
      cerebellovlivopontine atrophy, and might have important implications in the
      treatment of cerebellar ataxia in the future.

PMID- 9773072
TI  - [Epileptic seizures, epilepsy and risk factors. Experiences with an investigation
      in Martinique. Epimart Group].
AB  - A prospective incidence study was carried out in the French Caribbean island of
      Martinique between May 1st 1994 and April 31st 1995. incidence was 80.6 (77.7
      when standardized with 1990 U.S. population). This incidence was higher than that
      observed in the Swiss canton of Geneva where the same methodology was used. The
      individualized risk factors of first provoked and unprovoked seizures in
      Martinique were alcoholism, head trauma and cerebro-vascular accidents.

PMID- 9773071
TI  - [Residual deficit of verbal recall after a left internal cerebral vein infarct].
AB  - A case of unilateral infarct in the territory of the left internal cerebral vein,
      severely disturbing cognitive processes, and more especially recall in verbal
      memory, is reported. This 22-year-old patient survived a left thalamic and
      striato-capsular infarct related to a straight sinus and left internal cerebral
      vein thrombosis. Motor and functional recovery was fair, despite late dystonia.
      At the secondary phase post-stroke, cognitive disorders were severe, including
      increased short-term forgetting and episodic (anterograde and retrograde) and
      semantic amnesia. One year later, a residual deficit of verbal recall was
      observed, which participated in the anterograde and retrograde amnesia.
      Recognition was well preserved. This case showed that: (1) internal cerebral vein
      thrombosis can have severe consequences on cognition and memory, and that late
      prognosis is not as fair as has been previously reported in selected patients,
      and (2) left diencephalic structures are specifically associated with
      recollection of verbal information from long-term memory.

PMID- 9773073
TI  - [Neurologic complications of varicella in adults].
AB  - Three patients aged 32, 30 and 36 years, had chicken pox then developed acute
      cerebellar ataxia (for two) and acute polyradiculoneuritis. Cerebrospinal fluid
      (CSF) protein content was increased and varicella virus serology was positive in
      both blood and CSF. All three patients improved with aciclovir.

PMID- 9773074
TI  - [Fulminant orthochromatic leukodystrophy in an adult].
AB  - A 27-year-old man from Marocco developed a progressive dementia leading within a
      year to a mutic akinetic state. The course of the disease was also marked by
      epileptic seizures. MRI revealed diffuse white matter involvement. A frontal
      white matter brain biopsy was consistent with the diagnosis of orthochromatic
      leucodystrophy, i.e: presence of sudanophilic lipids and pigmented cells
      associated with myelin loss. Adult forms of orthochromatic leucodystrophy are
      very rare. Our case was characterized by a fulminant course.

PMID- 9773075
TI  - [Cranial pachymeningitis or unknown origin].
AB  - Pachymeningitis of unknown origin is uncommon and is usually associated with
      headaches, cranial nerve lesions and cerebellar ataxia. Magnetic resonance
      imaging is particularly contributive to diagnosis. The default diagnosis must
      however be confirmed by brain biopsy. Treatment is not well defined. Basically,
      corticosteroid therapy, or immunosuppressive therapy in case of failure, is known
      to have little effect on the brain lesion. We report here a case characterized by
      headache associated with partial regression of the radiographic lesions.

PMID- 9773076
TI  - [Propriospinal myoclonus induced by relaxation and drowsiness].
AB  - Propriospinal myoclonus is a subtype of spinal myoclonus characterized by axial
      flexion or extension jerks, arrhythmic and prolonged muscle bursts with a pattern
      of activation consistent with a slow conduction within the propriospinal
      pathways. We describe a new idiopathic case of flexion propriospinal myoclonus
      occurring upon relaxation and drowsiness. This syndrome is to be added to the
      spectrum of movement disorders occurring during drowsiness.

PMID- 9773077
TI  - [Magnetic resonance imaging of the facial nerve in a case of Melkerson-Rosenthal
      syndrome].
AB  - A 35-year-old man treated for a Crohn's disease presented with a second facial
      palsy in a setting of recurrent labial edema known since childhood. The diagnosis
      of Melkerson-Rosenthal syndrome was established. MRI showed a small T1 gadolinium
      enhanced lesion of the facial nerve suggesting an inflammatory process.
      Similarities of pathologic lesions found in Melkerson-Rosenthal syndrome, Crohn's
      disease and sarcoidosis raise the question of the relationships between these
      disorders.

PMID- 9773078
TI  - [Enterovirus meningitis in an adult].

PMID- 9773079
TI  - ["Stiff-man" syndrome treated with intravenous immunoglobulins].

PMID- 9773080
TI  - [Consensus statement of an interdisciplinary group of French experts on
      modalities of diagnosis and medical treatment of Alzheimer's disease at a
      treatable stage].
AB  - A group of French expert met on the 7th and 8th of February 1998 in order to
      establish a consensus attitude for Alzheimer's disease diagnosis and treatment.
      Members were drawn from primary care, geriatrics, neurology and psychiatry. They
      used the consensus statement of the American Association for Geriatrics, the
      Alzheimer's Association and the American Geriatrics Society published in JAMA, in
      October 1997 as a source of data for further consideration. Alzheimer's disease
      in the most common etiology of dementia. Main clinical features are cognitive
      impairment and psycho-behavioral disorders. Diagnosis must be one of inclusion
      and not exclusion. It is based on interviews of informants and family members and
      office-based clinical assessment. After a physical examination, cognitive
      function must be evaluated using the Mini-Mental State Examination. A laboratory
      evaluation should include a complete blood cell count, blood chemistry and
      determination of thyroid-stimulating hormone. In addition, noncontrast computed
      tomography head scans are adequate in most cases. Available pharmacologic
      treatments are not curative but are given to improve quality of life and enhance
      cognition and behavior. Two cholinesterases inhibitors, tacrine and donepezil,
      are the only agents officially authorized for treatment of the cognitive
      impairment in Alzheimer's disease. Mood and behaviour disorder also have to be
      treated by both pharmacologic and nonpharmacologic strategies. Only pharmacologic
      treatments will be detailed here. The consensus statements established by this
      group of experts will be reevaluated each year, considering the new available
      data on Alzheimer's disease.

PMID- 9773081
TI  - The hypomyelinating neuropathies of mice and men.

PMID- 9773082
TI  - [Arachnoid cysts: histologic, embryologic and physiopathologic review].
AB  - Arachnoid cysts form a cavity containing a cerebrospinal-like fluid, the wall of
      which is composed of arachnoidal cells. Other types of intracranial cysts have
      been described, they differ from arachnoid cysts by the histological
      characteristics of their wall. To analyze homogeneous series, it is thus
      necessary to differentiate arachnoid cysts from the other types of cysts. Several
      localizations of these lesions have been described: the most frequent being the
      temporo-sylvian area. Arachnoid cysts are considered as resulting from congenital
      malformations that can change during postnatal life. They can no longer be
      considered as resulting from cerebral atrophy. This arachnoid malformation could
      be the primary event or be explained by an impairment of the cerebrospinal fluid
      drainage generated by venous agenesis. Several mechanisms could account for the
      inflation of these cysts: secretion by the cells forming the cyst walls,
      unidirectional valve, liquid movements secondary to pulsations of the veins.

PMID- 9773083
TI  - [Unverricht-Lundborg disease: clinical and electrophysiologic study of 19 Maghreb
      families].
AB  - We describe clinical, electrophysiological and genetic features in 44 patients
      with Unverricht-Lundborg disease from 19 families living in North African
      countries (Tunisia, Algeria and Morocco). The mean age of patients was 25.3
      years; mean age was at onset 11.3 years. The disease began more frequently with
      seizures (91 per cent) or myoclonus (80 p. 100) than ataxia (16 p. 100).
      Subsequently myoclonus and generalized seizures were present in all patients,
      cerebellar signs were absent in four cases. EEG findings included normal
      background activity (90 p. 100), spontaneous fast generalized spikes (93 p. 100)
      and photosensitivity (70 p. 100). Antiepileptic polytherapy (clonazepam and/or
      phenobarbital and/or valporic acid) was used in 84 per cent of cases.
      Antiepileptic drugs were more effective in controlling epileptic seizures (less
      than one seizure/month in 60 p. 100) than myocloni which persisted daily in 64 p.
      100 of cases. Mean duration of the disease was 13.5 years. One patient died of
      status epilepticus. Consanguinity was noted in 17 families (first degree in 15
      families). Linkage to chromosome 21q 22.3 was confirmed in 11 families. We noted
      an inter and intrafamilial variability of clinical signs and disease course.

PMID- 9773084
TI  - [Learning disorders after ruptured aneurysms of the anterior communicating
      artery].
AB  - The aim of this study was to reevaluate short term and long term memory disorders
      after anterior communicating artery rupture, then to more specifically assess the
      importance and the role of forgetting, proactive and retroactive interferences,
      impaired memory for temporal order, attention disorders and dysexecutive
      syndrome, and finally MRI-defined brain lesions. Twenty one patients presenting
      with selective anterior brain injury, were assessed at the secondary and late
      post stroke phases. The short term memory analysis showed the digit span was
      reduced at the secondary stage, but that mean performances were preserved in the
      Peterson and Sternberg paradigms. Verbal and visuospatial learning in long term
      memory showed a severe deficit in free recall, chiefly serial, and associative
      recall. Recognition was mildly impaired at the secondary phase, and later
      normalized. A definite and lasting increase of proactive and retroactive
      interferences and an impairment in discriminating the temporal order of word
      presentations were observed. Amnesic impairment was relatively well correlated
      with forgetting, severity of interferences and temporal order amnesia, so as with
      disorders of attention and executive functions (Wisconsin Card Sorting Test).
      However, intrusions in free recall and false recognitions were not clearly
      related with the dysexecutive syndrome. The severity of amnesia was associated
      with lesions of the left anterior cingulate cortex, and of the corpus callosum.
      These results suggest that these patients mainly had a deficit in information
      retrieval, mostly compromising long term memory, but also to a lesser degree
      short term memory. Forgetting, interferences and the dysexecutive syndrome
      probably play an important role in the decline of mnemonic performance, but do
      not clearly explain intrusions in recall and errors in recognition.

PMID- 9773085
TI  - [Clinical assessment of dysarthria: presentation and validation of a method].
AB  - We adapted in French the Frenchay Dysarthria Assessment (FDA) developed by P.
      Enderby in 1983. This tool quantitatively evaluates the organs involved in speech
      and provides a measurement of intelligibility. Productions of normal subjects
      were analyzed. Reproductibility of data (correlation and interobserver
      concordance) was high in 18 dysarthric patients. A study performed in 100
      dysarthric patients corresponding to 4 types of dysarthria (spastic, ataxic,
      hypokinetic and mixte) showed that dysarthria resulted from a global impairment
      of organs implied in speech, rather than one specific organ. The reduction in the
      intelligibility score was related to organ impairment.

PMID- 9773086
TI  - [Persistence of point-waves in the encephalogram (EEG) in idiopathic generalized
      epilepsy and therapeutic decisions].
AB  - We reviewed the literature on the following issues in idiopathic generalized
      epilepsy, is there a correlation between the persistence of seizures and
      electroencephalographic anomalies? Do point-waves observed in well-controlled
      patients constitute a factor predicting relapse? Do changes in paroxysmal
      anomalies during the disease course mean poor prognosis? Actually, there is very
      little literature on these issues and some disagreement in those data which have
      been published. Documented studies have been conducted in search of factors
      predicting relapse at treatment withdrawal, but little has been published
      concerning the role of the EEG. Few studies specifically mention idiopathic
      generalized epilepsy. In terms of the syndrome studied, they concern
      heterogeneous groups of patients. Generally, it is accepted that the EEG helps
      predict clinical course in idiopathic generalized epilepsy as it does in other
      epilepsies, given the characteristic EEG signs. This is true in patients under
      treatment and after treatment withdrawal. Risk errors were not however reported.
      II would appear reasonable to assume that no one EEG anomaly is determinant
      outside the clinical context.

PMID- 9773088
TI  - [Limbic encephalitis and SIADH revealing small-cell anaplastic lung cancer: MRI
      and immunologic findings].
AB  - Paraneoplastic limbic encephalitis (PLE) is a manifestation of clinico
      pathological entity encephalo-myelo-neuropathy associated with anti-neuronal
      antibodies type 1 (ANNA-1 also called anti-Hu). Isolated PLE is rare. We reported
      a case of PLE in a 61-year-old heavy smoker man. An inappropriate antidiuretic
      hormone secretion syndrome was associated. Cranial MRI showed hyperintensity in
      amygdalo-hippocampic regions on T2 weighted sequences which appeared hypointense
      on T1-weighted sequences without gadolinium enhancement. Anti-Hu antibodies were
      absent in serum and in CSF. Despite chemotherapy, he died 18 months after disease
      onset. Our patient presented PLE without myelonouropathy and without ANNA-1 which
      suggests a different immunopathology.

PMID- 9773087
TI  - [Intramedullary tuberculoma: a case report].
AB  - A fifty-year-old Portuguese man presented with a six-month history of low back
      pain, which initially was mechanical and slowly became inflammatory. Secondarily,
      he complained of right atypical sciatalgia. He did not report any fever, loss of
      weight, cough nor personal or familial history of tuberculosis. General
      examination was normal. Neurologic examination showed weakness of the extensors
      of the right leg, with a symmetric increased reflexes of the lower extremities
      suggesting a pyramidal syndrome without Babinski's sign. Laboratory data were
      normal as well as chest radiographs. Dorsolumbar gadolinium enhanced MRI revealed
      an intramedullary ringlike enhancing mass at T12 level. Lumbar puncture showed 11
      WBC/mm3 (95 p. 100 lymphocytes), a normal protein and glucose content. PCR and
      culture for Mycobacterium tuberculosis were negative. Within a few days, he
      developed meningoencephalitis with fever, CSF examination revealed then 360
      WBC/mm3 (65 p. 100 lymphocytes and 17 p. 100 neutrophils), a protein content of 7
      g/l and a glucose level of 1.7 mmol/l. The clinical picture was then suggestive
      of tuberculosis and a specific therapy with rifampin, izoniazid, pyrazinamid,
      ethambutol and steroids was started. Clinical improvement and a second CSF
      culture that revealed one month later Mycobacterium tuberculosis complex
      confirmed this diagnosis. Ten months later, the patient was asymptomatic with a
      normal MRI. To our knowledge, this is the first total recovery of an
      intramedullary tuberculoma on medical therapy alone, confirmed by MRI
      normalization. We reviewed also 19 recent cases of tuberculomas in the
      literature, intending a therapeutic attitude when discovering an intramedullary
      ringlike enhancing mass on MRI.

PMID- 9773089
TI  - [Meningoradiculitis revealing an occult medulloblastoma-PNET in an adult].
AB  - Neoplastic meningitis as the presentation of occult primitive neuroectodermal
      tumor (PNET) is occasionally described in children. We report the case of an 64
      year old-man who presented a meningo-radiculopathy with progressive injury of the
      cauda equina and then the ocular motor nerves, revealing an occult
      medulloblastoma-PNET.

PMID- 9773090
TI  - [Cerebellar degeneration following acute lithium intoxication].
AB  - Lithium is a neurotoxin with a particular affinity for the cerebellum. The risk
      of permanent neurotoxic sequelae of lithium is increased by the concomitant use
      of certain conventional neuroleptics. We report two new cases of lithium
      neurotoxicity; one received lithium alone, not in combination with a neuroleptic.
      Both cases showed severe cerebellar atrophy on brain CT and MRI. Additional
      factors such as dehydration, systemic infection, other medications, or rapid
      correction of frequently-coexisting hyponatremia may contribute to the risk of
      lithium neurotoxicity. We discuss possible pathophysiologic mechanisms and
      preventive measures.

PMID- 9773092
TI  - [Irritation...].

PMID- 9773091
TI  - [Cerebrospinal fluid complement and antinuclear antibodies in lupus
      meningoencephalitis].
AB  - Central nervous system involvement in systemic lupus erythematosus (SLE) requires
      immediate treatment. We report a case in a 30-year-old woman. Clinical features
      associated asthenia, headache, right nystagmus and coma. A mechanical ventilation
      was started. The neurologic pattern appeared three months after an initial
      treatment with pulsed doses of glucocorticoid (500 mg per day for 3 days) and one
      month after an oral cyclophosphamid regimen (50 mg twice a week). The cerebral
      involvement was evidenced by MRI and comparative analysis of the antinuclear auto
      antibodies (ANA) and the complement components in cerebral spinal fluid (CSF),
      pleural fluid and serum. The MRI slices showed a well-defined meningeal focal
      lesion. CSF-cell count was normal. CSF-proteins were elevated. ANA were positive,
      total complement (UI/l) was low, C4 component (g/l) was 0.11, undetectable and
      0.25 respectively in plasma, CSF fluid and pleural fluid. The ANA specific
      pattern was anti-Sm2. We affirmed that specific cerebral injury was present
      because there were clinical and imaging features and a decrease of the C3 and C4
      component in the CSF. The treatment associated in travenous pulsed doses of
      methylprednisolone (1000 mg per days for 3 days) and cyclophosphamid (500 mg per
      day for three days). Mechanical ventilation was with drawn one day after the end
      of the pulse therapy. The diminution of the complement component could help
      improving cerebral involvement of SLE. More clinical studies are required.

PMID- 9773093
TI  - [Management of polyneuropathy].

PMID- 9773094
TI  - [Do 'chondroprotective agents' agents exist in osteoarthritis? Required proof].
AB  - The term 'chondroprotective agent' must be dropped in favour of that of structure
      modifying drug which allows consideration of the global process of osteoarthritis
      (OA). A structure-modifying drug is defined as being able to prevent, retard,
      stabilize or even reverse all or a part of the lesions of bone and cartilage
      which form the structure of human OA. The demonstration of an eventual structure
      modifying effect can only be provided by the proof of a favourable result on the
      anatomical lesions of OA. The measurement of joint-space narrowing by manual
      'radiochondrometry' or performed by computer is presently the 'method of choice',
      but requires the strict respect of standardized rules during the radiographic
      procedure. MRI may allow, in the future, a satisfactory assessment of the volume
      of articular cartilage. Chondroscopy permits a direct evaluation of lesions but
      is an invasive technique. Molecular markers still lack reliability. Until now, no
      drug has been able to provide well-established proof of a real effect of
      structuromodulation.

PMID- 9773095
TI  - [Do some drugs have adverse effects on cartilage?].
AB  - The potential chondrotoxicity of drugs is very difficult to appreciate because of
      the difficulties involved in evaluating the evolution of cartilage in human
      beings. This article attempts to summarize the data from the literature
      concerning the hypothetical chondrotoxicity of non steroidal anti-inflammatory
      drugs, fluoroquinolones, intra-articular injections of corticosteroids, and other
      drugs.

PMID- 9773096
TI  - [Cellular bases of neurodegenerative processes].
AB  - Neurodegenerative processes are generally characterized by the long-lasting
      course of neuronal death and the selectivity of the neuronal population or brain
      structure involved in the lesion. This is the case for Alzheimer's, Parkinson's
      or Huntington's diseases, or amyotrophic lateral sclerosis (ALS). The reasons for
      such a specificity are largely unknown as are generally the mechanisms of the
      diseases. One common feature of these diseases, however, is that the neuronal
      death is thought to involve apoptosis, at least partly. Interestingly, apoptosis
      in the brain would involve specific gene products similar to that identified in
      the nematode c. elegans, partly corresponding in mammals to ICE-related compounds
      and Bcl2 protein. The involvement of calcium as well as of oxydative stress
      mechanisms in such neuronal death is to be fully proved but putative modulation
      by external signals (such as those provided through trophic factors or even
      neurotransmitters) represents an interesting way to validate the current
      hypothesis of neuronal death in neurodegenerative diseases in humans.

PMID- 9773097
TI  - [Pharmacology of neurodegenerative diseases: perspectives on cellular and gene
      therapies].
AB  - Treatment of degenerative diseases includes neuroprotective strategies. Among
      these, the importance of the different neurotrophic factors has been demonstrated
      but the remaining difficulty is the way of administration. It is important to
      find new strategies in cell and gene domains. Cell ex vivo therapy and gene in
      vivo therapy are under development but must be confirmed by clinical trials.

PMID- 9773098
TI  - [Pharmacologic approach to autonomic failure].
AB  - Four different forms of primary autonomic failure (multiple system atrophy, pure
      autonomic failure, Parkinson's disease and dopamine beta-hydroxylase deficiency)
      have been described. The first part of the article will focus on the interest to
      pharmacology of elucidating pathophysiological mechanisms underlying autonomic
      involvement at the central level (growth hormone response to clonidine acute
      challenge), presynaptic level (plasma catecholamine levels after yohimbine
      administration) and on post-synaptic receptors (binding studies, pressor
      responses to noradrenaline). The second part will discuss efficacy and side
      effects of some of the many drugs which are currently proposed for the treatment
      of one of the most disabling symptoms related to autonomic failure, orthostatic
      hypotension. Special attention will be paid to drugs acting on blood composition
      (fludrocortisone, erythropoietin), on post-synaptic alpha-adrenoceptors
      (midodrine and clonidine) and on noradrenaline spill-over (yohimbine and L-Threo
      DOPS).

PMID- 9773099
TI  - [Clinical pharmacology of dyskinesias induced by L-dopa in Parkinsonian
      patients].
AB  - Dyskinesias induced by L-dopa are involuntary and abnormal movements which lead
      to disablement and are observed in a lot of patients after some years of
      treatment. No drug has proved its efficacy for this indication. The use of D2
      dopaminergic agonists as first treatment can delay their onset, delaying the need
      for L-dopa. New dopaminergic drugs, either with longer elimination half life or
      with specificity for subtypes of dopamine receptors may allow these dyskinesias
      to be managed more efficaciously. New non-dopaminergic, serotoninergic,
      adrenergic, opiate or gluamate drugs could offer antidyskinesia properties. The
      study of Parkinson disease's model in the methyl phenyltetrahydropyridine (MPT)
      treated primate and the improvement in clinical evaluation of these dyskinesias
      could lead, in the short or medium term, to the discovery of new pharmarcological
      strategies, dealing more efficaciously with this serious adverse effect of L-dopa
      treatment.

PMID- 9773100
TI  - [Why has menopause become a public health problem?].
AB  - Menopause is a very important public health problem for many reasons.
      DEMOGRAPHIC: In 1990 there were 467 million women aged 50 years or more;
      worldwide, they will number 1200 million in 2030. SOCIOLOGICAL: The expectation
      of life in the Occident for a 50-year-old woman is a further 33 years, thus at
      this point, a menopausal women is still in active employment. PHYSIOLOGICAL:
      Menopause is not a disease, but gives rise to many problems which involve the
      entire body. MEDICAL: The only available treatment for this phase of the woman's
      life is oestrogens. These drugs induce many beneficial effects but the large
      scale treatment of women who are not ill brings into question the harmlessness of
      this approach. ECONOMIC: The cost of medical treatment and regular review have to
      be considered in addition to the increased cost of pensions for these women.
      HUMAN: The improved quality of life observed with the medical treatment of such
      women could be an added dimension of the classical evaluation of the benefit/risk
      ratio.

PMID- 9773101
TI  - [Uroselectivity of alpha-1 antagonism in the treatment of benign prostatic
      hypertrophy: on the pharmacologic concept of the clinical approach].
AB  - Benign prostatic hyperplasia is the most common cause of voiding dysfunction in
      men. It becomes symptomatic from the fifth decade of life and needs treatment in
      50 per cent of patients. Hyperplastic prostatic tissue and the smooth involuntary
      sphincter have a high density of alpha 1-adrenoceptors, thus alpha 1-blockers can
      decrease sphincter tone and reduce the tension exerted by the prostatic muscular
      component. Attempts have been made to find alpha 1-antagonists that have a
      selective effect on the prostate (alfuzosin), are long acting (tamsulosin,
      terazosin, doxazosin) or present specificity on the alpha 1A prostatic
      adrenoceptors (tamsulosin), in order to maintain efficacy without affecting blood
      pressure. Finasteride, a 5 alpha-reductase inhibitor without hypotensive side
      effect may be more effective in men with a predominantly glandular component to
      their benign hyperplasia or with very large prostate glands, but has a longer
      onset of action and produces more adverse sexual effects. Thus, alpha-1
      antagonists can be considered as an appropriate treatment option in patients with
      troublesome symptoms of BPH and who have not developed serious complications
      indicating surgery.

PMID- 9773102
TI  - [Balance sheet of tolerance-efficacy on the use of tacrine in 100 cases of
      Alzheimer's disease].
AB  - We report our first 100 cases of Alzheimer's (AD) patients treated with tacrine
      (Cognex) for a period of one year. At the beginning of treatment the mean Mini
      Mental-Status (MMS) score was 15.1. To date 71 patients are still under treatment
      (12 for more than 12 months). Forty-three instances of side-effects were
      observed, of which 31 involved hepatic side-effects with an increase in ALAT > IN
      (normal value) (6 cases > 3N), the mean date of appearance was 10.4 +/- 6.8
      weeks, there were 16 cholinergic side-effects (nausea, vomiting, diarrhoea), plus
      4 neurologic and 2 cutaneous side-effects. These side-effects led to the arrest
      of the treatment in 19 cases (16 for hepatic toxicity). Treatment was reattempted
      after interruption in 13 cases; successfully in 3 instances only. The measure of
      tacrine efficacy was based on 52 MMS score re-evaluations in week 18: there was
      an increase of the MMS score in 22 cases (3.3 points +/- 2.5), a stabilisation in
      11 cases and a decrease in 19 cases (3.3 points +/- 2.2.). In week 30, the MMS
      scores (35 patients) increased in 9 cases (3.6 points +/- 2.4), stabilized in 5
      cases and decreased in 21 cases (3.9 points +/- 3.3). At week 52, only 28 per
      cent of the patients were considered as either improved or stabilized. We
      conclude that there is a necessity for close follow-up of tacrine-treated
      patients, and that globally at 8 months there is an improvement or a
      stabilization in 40 per cent of patients and long term (at one year) a
      stabilizing effect on AD patients.

PMID- 9773103
TI  - [Hypersensitivity to azathioprine can simulate an aggravation of myasthenia].

PMID- 9773104
TI  - [Zopiclone and delirium: a case report].

PMID- 9773105
TI  - [Amfepramone intoxication].

PMID- 9773106
TI  - Fulminant hepatic failure after herbal medicine ingestion in children.

PMID- 9773107
TI  - [The non-conventional transmissible agents at the origin of transmissible
      subacute spongiform encephalopathies].
AB  - The transmissible subacute spongiform human encephalopathies are neurological
      diseases, always fatal and with a prolonged incubation time. In infected
      patients, an accumulation of a host protein from the genes, the prion protein, is
      observed in proportionality to the infectious load. The prion protein gene is the
      major determinant of the genetic susceptibility in relation to subacute
      spongiform encephalopathies. On neuropathological examination, patients have a
      characteristic triad: neuronal vacuolisation, neuronal death and glial reaction.
      The nature of agents involved in these subacute spongiform encephalopathies is
      not known. Most authors think that the causal agent is a pathological form of the
      PrP protein partially resistant to proteinase K (the prion). For others, it is a
      more classical structure including an independent genome for which the prion
      protein will be either the receptor or the virulent factor. The apparition of
      bovine spongiform encephalopathy in the United Kingdom and of the new variant of
      Creutzfelt-Jakob disease brings into question the discovery of new subacute
      spongiform diseases and involves the proposition of efficacious protective
      measures for public and animal health.

PMID- 9773108
TI  - [Preventive treatment of thrombosis: audit on heparin prescription].
AB  - An audit has been carried out, in a French general hospital, studying the use of
      heparins in preventive indications, to assess concordance between prescriptions
      and thrombotic risk, before and one year after the diffusion of national
      guidelines. Platelet monitoring frequency has also been studied. On a defined
      day, 550 patients were admitted, and 113 treated with preventive heparinotherapy
      (low molecular-weight heparin: 98 per cent). 52.2 per cent of patients received a
      correct regimen, while 4.4 per cent of underprescriptions and 43.4 per cent of
      overprescriptions were observed. Platelet monitoring protocol was respected in 44
      per cent of cases, while it was insufficient for 41 per cent and not carried out
      in 15 per cent. The results of this study have been communicated to all the
      prescriptors. Another audit done one year later showed that 81 per cent of doses
      were adapted to the thrombotic risk, 2 per cent were too low, and 17 per cent too
      high. The efficiency of this kind of process shows that it should be generalized
      to all the sensitive therapeutic classes.

PMID- 9773109
TI  - [Study of narcotics and buprenorphine prescriptions in the Provence-Alps-Cote
      d'Azur region].
AB  - Following the setting up by the Government of their project for the management of
      drug addicts, and under the guidance of the CEIP (Centre d'Evaluation et
      d'Information sur les Pharmacodependances [Centre for Evaluation and Information
      on Drug Addiction]) in Marseille, a survey of prescriptions written on controlled
      drug prescription pads was performed. The aims were threefold: to study the
      medicines prescribed, to follow up the legislation and to inform doctors and
      pharmacists. Copies of the prescriptions, dated between 1 January 1996 and 30
      June 1996, which were sent by 81 per cent of the 216 pharmacies contacted in 15
      towns in the Provence-Alpes-Cote d'Azur (PACA) region were studied. Various
      criteria, relating to writing of the prescriptions and distribution of the
      medicines to the patients, were coded and analysed. This survey showed that of 4
      prescriptions, 3 were prescribed for maintenance and one for analgesic therapy.
      The patients receiving maintenance therapy were male in three-quarters of the
      cases, and were around 30 years old. Analgesics were prescribed in equal
      proportions for patients of both sexes, who were around 65 years old. Since it
      was put on the market, Subutex has been quickly prescribed.

PMID- 9773110
TI  - [Drug prescription and utilization in Morocco].
AB  - The aim of this study was to assess drug prescription and utilization in Morocco
      8 years after the statement of the Action Program for Essential Drugs. To
      evaluate the role of essential drugs in these prescriptions, a study of about 600
      prescriptions and questionnaires sent to a random sample of 111 prescribers and a
      series of visits with the investigator as a neutral observer was undertaken. The
      average number of drugs prescribed was 3.27, which reflected the feelings of most
      of the clinicians, for whom 3 drugs per patient is the required number. The
      number of drugs prescribed is lower in the public health structure (2.0 +/- 0.14
      depending on the type of institution: hospital or primary health care centre).
      Specialties from the national list of essential drugs accounted for 15.48 per
      cent of all drugs which is to be compared with 16.2 per cent of the clinicians
      stating knowledge of the action programme for essential drugs. In public
      structures, these prescriptions ranged between 29.8 per cent and 82.4 per cent of
      the essential drugs (WHO general list). The length of the visit ranged between
      3.27 +/- 0.96 min and 4.87 +/- 1.04 min according to the health centres and
      prescriptions included at least one antibiotic in 47.5 per cent of cases (25 per
      cent to 64 per cent). At least one antibiotic was prescribed in 43.3 per cent of
      cases in the study of prescriptions and 17.3 per cent of prescriptions included
      at least one injectable drug. The average cost of one prescription was 146.25
      dirhams (ranging between 4 and 1200 dirhams = US $17). According to 68.6 per cent
      of the prescribers, the patients felt there to be a strong relation between
      efficacy and cost. Among the prescription motivations, cost ranked above
      availability of the drug and after efficacy.

PMID- 9773111
TI  - The kinetic profiles of amlodipine and of a sustained release form of diltiazem.
AB  - This study in normotensive subjects compared plasma concentrations of amlodipine
      (5 mg) and of a sustained release form of diltiazem (300 mg) after single and
      multiple oral dosings of the two drugs. As a consequence of the galenic form of
      administered formulations, plasma concentration of diltiazem versus time curves
      exhibited two peaks corresponding to fast and slow releases of diltiazem.
      Conversely, the curves of amlodipine plasma concentration depicted only one peak.
      There was less variability in plasma concentrations and in pharmacokinetics with
      amlodipine than with diltiazem after both single and multiple oral dosings of the
      two drugs. These results suggested that amlodipine displayed less variability in
      blood pressure response at steady-state. The rate of decrease in plasma levels of
      diltiazem between 24 and 48 hours post-dose was higher than that of amlodipine.
      So, even after a missed dose, there is only a small decline in plasma
      concentrations of amlodipine and therefore it suggests a small repercussion on
      the blood pressure attenuation.

PMID- 9773112
TI  - [Investigation on self-medication: from disease to performance].
AB  - Self-medication is widely practised and could be defined as taking drugs without
      the advice of a physician. The present survey documented self-medication users'
      profile and their drug-taking behaviour. EXPERIMENTAL DESIGN: prospective study
      by self-report questionnaire. PARTICIPANTS: 600 residents of the Meurthe et
      Moselle subdivision (eastern France), ranging in age from 15 to 85 years,
      including 288 males and 312 females. MEASURES: use and impressions of self
      medication, based on the subjects' own experience. DATA ANALYSIS: questionnaires
      were coded and put on computer. The data were analysed and compared by chi-square
      and analysis of variance. Statistical significance was accepted at p < 0.05.
      RESULTS: 313 subjects (52.2 per cent) reported having used self-medication. The
      three main motives for this practice were: headache (46.9 per cent), nose, throat
      or respiratory tract diseases (22.1 per cent) and abdominal pain (7.3 per cent).
      Self-use of drugs usually involved left-over past prescribed treatment (76 per
      cent), or were bought without the advice of a pharmacist (28 per cent). The self
      medication user tends to be a woman, ranging in age from 20 to 39 years, living
      in a marital relationship and resident in an urban zone. The behaviours leading
      to self-medication were studied. Five groups are described, probably associated
      with five different attitudes towards self-medication. One of them shows subjects
      who essentially use drugs not to treat a disease but to enhance their
      performance.

PMID- 9773113
TI  - [Cutaneous side effects of ketoprofen gels: results of a study based on 337
      cases].
AB  - Ketoprofen gels, since their introduction on the French market (1989), have been
      responsible for various cutaneous side-effects (essentially photosensitization
      and contact eczemas). A study conducted by the French drug surveillance system
      detected 337 cases. Analysis showed that the frequency of cutaneous adverse
      events was from 0.008/1000 to 0.023/1000 according to the commercial gel. The sex
      ratio was well distributed, and the population was young (30-40 years) and
      athletic. Treatment lasted about 7 days, and the appearance of the side-effect
      was sometimes quite delayed relative to discontinuance of treatment. Reactions
      were severe in 40 per cent of cases. The factors favourable to side-effects were
      essentially exposure to the sun (one-third of cases) and occlusive dressing. No
      particular predisposing conditions were noted, although 2.6 per cent and 8.5 per
      cent of cases respectively involved earlier sensitization by a topical NSAID. The
      side-effect lasted about 16 days. The course was usually favourable but
      hospitalization was required in about 10 per cent of cases. Photoallergological
      testing indicated photosensitization to ketoprofen. These results led the
      National Commission of the French drug surveillance system to request a
      modification in the indications for the prescription of the ketoprofen gels.

PMID- 9773114
TI  - Points of view on adverse drug reactions terminology.
AB  - Global management of drug safety data is the best way to make the detection and
      validation of adverse drug reactions (ADRs) earlier. Centralization needs a
      previous standardization, of which terminology is a crucial component. ADR
      terminology must be designed so as to enable users to know exactly what is
      covered by each term regarding the nature of the reaction and its significance
      for public health. A worldwide standardized terminology for all drug reporting
      purposes is currently being developed by the International Conference on
      Harmonization of Technical Requirements for Registration of Pharmaceuticals for
      Human Use. However, practical definitions of medical terms will be necessary and
      could be developed by specialists on drug safety in collaboration with
      specialists of different system organs, as has already been achieved for some of
      them.

PMID- 9773115
TI  - [PHOLY: A pilot study of drug utilization in civil hospices in Lyon - methodology
      and difficulties].
AB  - PHOLY is a study of drug Prescription in Hospices civils of LYon by a transverse
      and descriptive survey. It aims at studying the methodology of such an
      investigation in a large university medical centre, elaborating a methodology for
      continuous assessment of prescribing, comparing prescriptions with scientific
      knowledge and identifying specific therapies. We collected 1525 questionnaires
      from 4333 hospitalized patients in 11 hospitals (prescriptions and indications).
      The main difficulties we encountered concerned communications (4 letters), fewer
      questionnaires collected than expected (1525/3018), many missing data, and the
      lack of a specific budget, thus allowing only partial data exploitation and
      control. This study revealed many problems such as relevant information for
      physicians, training and management of investigators, control, data capture and
      analysis. However, a prescription study may be possible with limited means.

PMID- 9773116
TI  - [PHOLY: a pilot study of drug utilization in civil hospitals in Lyon. Results].
AB  - As shown in many studies, up-to-date knowledge is not reflected in prescribing
      behaviours. The aim of pilot study PHOLY (Prescription aux Hospices civils de
      LYon) was to study methodological and technical conditions of a drug utilization
      study in a large university medical centre and to evaluate the discrepancy
      between drug prescribing and up-to-date knowledge. Data of 1115 in-patients of
      Hospices Civils de Lyon were collected. We have shown the feasibility of such a
      study in spite of many difficulties (52.15 per cent of questionnaires received,
      missing data...). Reference treatments such as ACE inhibitors in heart failure
      treatment or betablockers for high blood pressure represent respectively only
      14.6 per cent and 6.7 per cent of the prescriptions in these indications. Within
      the framework of quality of care improvement, the study of the appropriateness of
      the treatments enables identification of domains where better therapeutic
      information is necessary.

PMID- 9773117
TI  - [Convulsions and circulatory arrest from fluvoxamine and paroxetine poisoning].

PMID- 9773118
TI  - [Convulsive crisis associated with an overdose of cefepime].

PMID- 9773119
TI  - [Angiotensin II receptors: classification, structure, and signal transduction].
AB  - Angiotensin II (AngII), a circulating vasoactive peptide, interacts with specific
      membrane-bound receptors on the target tissues (vessels, kidneys and adrenal
      gland). Using new pharmacological tools and molecular cloning, these receptors
      have been classified in two types, called AT1 et AT2, whereas two subtypes,
      called AT1A et AT1B, have been identified for the rodent AT1 receptors, but not
      in humans. All these receptors present a seven hydrophobic transmembrane domain
      structure, which is classical for G protein coupled receptors. The interspecies
      molecular homology of these AngII receptors is high (> 90 per cent identity)
      within the same type of receptor, but is rather low (approximately 35 per cent
      identity) between the two types of receptors. The AT1 receptors are responsible
      for most of the AngII physiological actions and are coupled to a Gq protein,
      which activates a phospholipase C producing second messengers which activate
      protein kinases C and mobilize calcium intracellular stores. More recently, a
      strong interaction of this receptor has been demonstrated with the signalling
      pathways of the tyrosine kinases. The molecular mechanisms and the physiological
      importance of these interactions remain to be elucidated. The intracellular
      signalling (Gi coupling and tyrosine phosphatase activation) and the
      physiological actions (cellular differentiation, apoptosis) of the AT2 receptors
      are more controversial.

PMID- 9773120
TI  - [Functions of AT2 receptors of angiotensin II].
AB  - The structure, the coding gene and expression of the AT2 subtype receptor of
      angiotensin II have been described recently; however, the possible role of this
      receptor remains unclear despite its presence in most mammalian tissues. The AT2
      receptor is probably involved in fetal growth and adult tissue repair and
      remodelling, especially in the cardiovascular system. There are still conflicting
      results, in vitro and in vivo, as to whether AT2 receptors limit and/or
      accelerate the growing processes in the cardiovascular tissues.

PMID- 9773121
TI  - [The cardiovascular steroid system].
AB  - In this review, the authors describe: (1) the different types of glucocorticoid
      hormone receptors, on the cell membrane and two types inside the cell, the MR and
      GR (mineralo- and glucoreceptors); (2) the synthesis of the hormones with the
      decisive role of the final enzymes, 11 beta-hydroxylase and aldosterone
      synthetase; (3) the increasing evidence for a cardiovascular steroid system in
      the vessels as well as in the myocardium. The authors have reported new data
      suggesting the existence of an endocrine cardiac steroidogenic system in the
      heart with a potential physiological and pathological relevance (for
      transmembrane ion transport and trophic alterations).

PMID- 9773122
TI  - [Aldosterone receptors: new insights in hormonal signal transduction].
AB  - Aldosterone exerts its effects by binding to an intracellular receptor, the
      mineralocorticoid receptor (MR), that belongs to the superfamily of ligand
      regulated transcription factors. This family includes receptors for steroid and
      thyroid hormones, vitamin D and retinoids and also orphan receptors with
      unidentified ligands. All the members of this family display a modular structure
      composed of a transactivation domain, a DNA binding domain and a ligand binding
      domain. Upon hormone binding, the receptor undergoes a series of structural
      modifications leading to its interaction with DNA sequences and transcriptional
      modulation of specific genes. Since the level of circulating glucocorticoids is
      100-1000 fold higher than that of aldosterone and the affinity of the MR is
      identical for glucocorticoids and aldosterone, the question of the mechanisms
      responsible for the in vivo selectivity of aldosterone for its receptor arises.
      The mechanisms of cellular and tissular selectivity involved in the physiological
      response of aldosterone are discussed in this review.

PMID- 9773123
TI  - [Aldosterone antagonists: new pharmacologic prospects].
AB  - The pharmacology of the mineralocorticoid receptor antagonist spironolactone and
      analogues is reviewed in the light of recent discoveries regarding the primary
      structure of corticosteroid receptors and the different isoforms of the enzyme 11
      beta-hydroxysteroid dehydrogenase. The type 2 isoform of this enzyme functions in
      some tissues to keep the aldosterone receptor activation specific, i.e. it allows
      stimulation by aldosterone while eliminating glucocorticoids such as cortisol and
      corticosterone. The type 2 isoform has been shown in the colon, hypothalamus,
      kidney, placenta and salivary gland. New clinical uses of aldosterone antagonists
      may be derived from these developments. Most prominent in this respect appear to
      be myocardial fibrosis and specific forms of hypertension with altered
      mineralocorticoid receptor functioning and deficiencies in the protection system
      of the receptor against glucocorticoids.

PMID- 9773124
TI  - [Interaction between the sympathetic and renin-angiotensin system].
AB  - The renin-angiotensin system is involved in the control of sodium and water
      balance, mitogenesis and the regulation of vascular tone as well as of the
      activity of the sympathetic nervous system. Many of these effects may be
      regulated at a local level by independent tissue renin-angiotensin systems. The
      renin-angiotensin and adrenergic nervous systems are cross-regulated by
      interactive compensatory mechanisms. Therefore, the activation of one of these
      systems induces the activation or induction of the other leading to a co
      amplification of cellular mechanisms, for instance resulting in the facilitation
      of sympathetic neurotransmission. This paper describes the interactions between
      these systems in the central nervous system and at pre- and postsynaptic sites of
      the nerve endings in cardiovascular tissues. Since these systems are cross
      regulated, the inhibition of one would attenuate the activity of the other. The
      drugs that inhibit specifically the various components of the renin-angiotensin
      system have proved powerful tools for studies of the physiology of this system as
      well as for the treatment of hypertension and heart failure.

PMID- 9773125
TI  - [Comparison between the effects of angiotensin-converting enzyme inhibitors and
      angiotensin II antagonists].
AB  - The renin-angiotensin-aldosterone system (RAAS) plays an important role in blood
      pressure regulation and fluid and electrolyte homeostasis. Angiotensin converting
      enzyme inhibitors (ACEI) were the first of the RAAS blocking agents to be widely
      used in the treatment of hypertension and congestive heart failure. Angiotensin
      II receptor antagonists, another class of pharmacological blockers of the RAAS,
      have more recently been shown to be safe and useful in hypertension and perhaps
      also in heart failure. This review deals with the similarities and differences
      between these two classes of drugs with particular emphasis on the effects of the
      drugs on the heart, the blood vessels, the kidney (role of the drugs as
      nephroprotective), the brain, the hormonal profile and finally the potential
      adverse effects. The place of angiotensin II antagonists in congestive heart
      failure remains to be more precisely defined.

PMID- 9773126
TI  - [Genetic polymorphisms in the renin-angiotensin system].
AB  - Gene coding for the main components of the renin-angiotensin system have been
      characterized and localized: angiotensinogen (AGT, chromosome 1q42), renin (REN,
      chromosome 1), angiotensin I-converting enzyme (ACE, chromosome 17), angiotensin
      II receptors (AT1R, chromosome 3 and AT2R, chromosome X). A positive linkage and
      association have been found between AGT and essential hypertension. M235T is also
      associated with plasma AGT concentration. In vitro studies suggest that a
      polymorphism (G-6A) which is in complete linkage disequilibrium with M235T and
      which is located in the promoter close to the start of transcription might
      explain this association with high blood pressure. The ACE I/D polymorphism
      explains about 30 to 40 per cent of the variance of plasma ACE levels. Although
      the ACE gene itself does not seem to play a role in blood pressure level, the
      corresponding chromosomal region has been linked to blood pressure in both
      spontaneously hypertensive rats and humans. In tissues, an increased ACE activity
      may explain the association between the ACE I/D polymorphism and coronary heart
      disease, left ventricular hypertrophy, neointimal proliferation in vessels and
      progression of diabetic and IgA nephropathy.

PMID- 9773127
TI  - [Angiotensin II AT1 receptor antagonists: clinical development and future
      perspectives].
AB  - Blockade of the renin-angiotensin system with angiotensin-converting enzyme (ACE)
      inhibitors is now recognized as an effective approach for the treatment of
      hypertension and congestive heart failure. In addition, ACE inhibitors are very
      effective for the prevention of chronic renal failure. Today, it is possible to
      antagonize the effects of angiotensin II more specifically using AT1 receptor
      antagonists. Several non-peptide, orally active angiotensin II receptor
      antagonists have recently been developed clinically. These new molecules are as
      effective as ACE inhibitors, calcium antagonists and beta-blockers at reducing
      blood pressure in hypertensive patients. Furthermore, they appear to have similar
      systemic and renal hemodynamic properties in patients with congestive heart
      failure and renal diseases. Now, several large clinical trials such as the LIFE,
      the RENAAL and the ELITE II studies are under way to investigate the long-term
      benefits of one of these compounds in hypertension, heart failure and type II
      diabetic nephropathy.

PMID- 9773128
TI  - [Renin-angiotensin-aldosterone system and heart failure: therapeutic aspects].
AB  - Renin, angiotensin II and aldosterone levels are elevated in congestive heart
      failure, especially when diuretics are introduced. This activation is clearly
      deleterious by elevating myocardial workload and is related to prognosis of heart
      failure. The link between hormonal activation and prognosis is causal, as
      hormonal inhibition by converting enzyme inhibitors improves heart failure
      prognosis. Angiotensin II and aldosterone appears to be toxic for the myocardium.
      The results of the trial conducted with angiotensin II antagonist losartan
      confirm data derived from converting-enzyme-inhibitors trials. The exact role of
      aldosterone is currently being evaluated in the RALES programme.

PMID- 9773129
TI  - [Renin-angiotensin-aldosterone system inhibition: pharmacologic rationale and
      evaluations of drug combinations].
AB  - First-line antihypertensive monotherapy is effective in normalizing blood
      pressure in approximatively 50 per cent of patients. Normalization in the
      remaining patients may require a combination of two or more drugs. This review
      considers the rationale and the evaluation of combinations with drugs interacting
      with the renin-angiotensin system (i.e. angiotensin-converting enzyme inhibitors
      (ACEI) and angiotensin receptor antagonists) with other drugs. The combinations
      may be justified when giving an additive or synergistic action and when reducing
      clinical or metabolic side-effects. Recent developments concern the potential
      benefit of combining ACEI and angiotensin receptor antagonists.

PMID- 9773130
TI  - Effects of anxiety on emotional reactivity, performance and vigilance, in healthy
      volunteers.
AB  - Healthy volunteers who participate in clinical trials usually present a specific
      personality profile characterized by high extroversion and low anxiety traits.
      Herein, we examined whether anxiety traits influence performance and vigilance,
      as well as reactivity for six emotions (fear, anger, disgust, sadness, happiness
      and a neutral state), the latter being induced by the presentation of six film
      excerpts. Sixty-four healthy volunteers were stratified into high and low anxiety
      groups on the basis of their score on the Cattell and Hamilton Anxiety Scales.
      They were assessed on the Digit Symbol Substitution Scale (DSST), Choice Reaction
      Time (CRT) and Visual Analogue Scales (VAS). Their emotional reactivity was
      evaluated before and after each film excerpt, on responses to the Differential
      Emotions Scale (Izard DES). Prior to emotional induction, high-anxious subjects
      presented a pattern of low positive emotions and high negative emotions. After
      each film excerpt, emotional reactivity was more pronounced for high-anxious
      subjects compared with low-anxious subjects. However, there were no significant
      interactions between anxiety level and the values of DSST, CRT or VAS. The
      present findings raise the question of the relevance of selecting healthy
      volunteers according to their personality traits. In future studies, anxiety
      level will be further investigated as a factor of response variability to drugs,
      by examining differences in response to psychotropic drugs as a function of this
      factor.

PMID- 9773131
TI  - Ropivacaine: a new agent for epidural labour analgesia?

PMID- 9773132
TI  - Pharmacokinetics and clinical effect during continuous epidural infusion with
      ropivacaine 2.5 mg/ml or bupivacaine 2.5 mg/ml for labour pain relief.
AB  - BACKGROUND: Ropivacaine has shown less systemic toxicity than bupivacaine, and
      comparatively low muscle-blocking properties could constitute another advantage
      when used epidurally for obstetric pain relief. We aimed primarily to compare
      maternal and foetal drug disposition following continuous epidural infusion of
      ropivacaine or bupivacaine. METHODS: Twenty-four full-term, nulliparous women
      were randomized to continuous epidural infusion (10 ml/h) of ropivacaine 2.5
      mg/ml or bupivacaine 2.5 mg/ml for labour pain relief in a double-blind, parallel
      group design. Maternal blood samples were collected up to 24 h after the end of
      infusion as well as taken from the umbilical cord at the time of delivery.
      Sensory and motor block as well as analgesia were assessed. All the women were
      monitored by cardiotocography and neonatal assessment was performed. RESULTS: The
      sensory block was adequate for both drugs. Higher plasma levels (total and free)
      were seen with ropivacaine, although the infusion with bupivacaine continued on
      average for about 2 hours longer. However, the ratios between maternal and
      umbilical blood concentrations were similar for both drugs. Normal neonatal Apgar
      and neonatal adaptive capacity scores (NACS) were found in both groups.
      CONCLUSION: A continuous epidural infusion of 25 mg/h ropivacaine or bupivacaine
      both produced good labour pain relief. Higher total and free plasma
      concentrations were seen for ropivacaine. The ratios between maternal and
      umbilical plasma levels were similar for both drugs.

PMID- 9773133
TI  - Adrenaline markedly improves thoracic epidural analgesia produced by a low-dose
      infusion of bupivacaine, fentanyl and adrenaline after major surgery. A
      randomised, double-blind, cross-over study with and without adrenaline.
AB  - BACKGROUND: Basic pharmacological research indicates that there are synergistic
      antinociceptive effects at the spinal cord level between adrenaline, fentanyl and
      bupivacaine. Our clinical experience with such a mixture in a thoracic epidural
      infusion after major surgery confirms this. The objectives of the present study
      were to evaluate the effects on postoperative pain intensity, pain relief and
      side effects when removing adrenaline from this triple epidural mixture. METHODS:
      A prospective, randomised, double-blind, cross-over study was carried out in 24
      patients after major thoracic or abdominal surgery. Patients with only mild pain
      when coughing during a titrated thoracic epidural infusion of about 10 ml.h-1 of
      bupivacaine 1 mg.ml-1, fentanyl 2 micrograms.ml-1, and adrenaline 2 micrograms.ml
      1 were included. On the 1st and 2nd postoperative days each patient was given a
      double-blind epidural infusion, at the same rate, with or without adrenaline. The
      effect was observed for 4 h or until pain when coughing became unacceptable in
      spite of a rescue analgesic procedure. Rescue analgesia consisted of up to two
      epidural bolus injections per hour and i.v. morphine if necessary. All patients
      received rectal paracetamol 1 g, every 8 h. Fentanyl serum concentrations were
      measured with a radioimmunoassay technique at the start and end of each study
      period. Main outcome measures were extent of sensory blockade and pain intensity
      at rest and when coughing, evaluated by a visual analogue scale, a verbal
      categorical rating scale, the Prince Henry Hospital pain score, and an overall
      quality of pain relief score. RESULTS: The number of hypaesthetic dermatomal
      segments decreased (P < 0.001) and pain intensity at rest and when coughing
      increased (P < 0.001) when adrenaline was omitted from the triple epidural
      mixture. This change started within the first hour after removing adrenaline.
      After 3 h pain intensity when coughing had increased to unacceptable levels in
      spite of rescue analgesia (epidural bolus injections and i.v. morphine). Within
      15-20 min after restarting the triple epidural mixture with adrenaline, pain
      intensity was again reduced to mild pain when coughing. Serum concentration of
      fentanyl doubled from 0.22 to 0.45 ng.ml-1 (P < 0.01), and there was more
      sedation during the period without adrenaline. CONCLUSIONS: Adrenaline increases
      sensory block and improves the pain-relieving effect of a mixture of bupivacaine
      and fentanyl infused epidurally at a thoracic level after major thoracic or
      abdominal surgery. Serum fentanyl concentrations doubled and sedation increased
      when adrenaline was removed from the epidural infusion, indicating more rapid
      vascular absorption and systemic effects of fentanyl.

PMID- 9773134
TI  - Epidural fentanyl, adrenaline and clonidine as adjuvants to local anaesthetics
      for surgical analgesia: meta-analyses of analgesia and side-effects.
AB  - BACKGROUND: The risk/benefit ratio of adding fentanyl, adrenaline and clonidine
      to epidural local anaesthetics for improving intraoperative analgesia is unclear.
      This meta-analysis was performed to clarify this issue. METHODS: Trials retrieved
      by search were considered if they were prospective, controlled, epidural
      analgesia (without combining general anaesthesia) was planned and occurrence of
      pain during surgery or side-effects were reported. Papers entered meta-analysis
      if they reached a predefined minimum quality score. Pooled odds ratios (OR) and
      confidence intervals (CI) were computed. P < 0.05 was considered as significant.
      RESULTS: Eighteen trials were included in the analysis for fentanyl. Fentanyl
      decreased the likelihood of pain (OR = 0.21, 95% CI = 0.15-0.30, P < 0.001) and
      increased the incidence of pruritus (OR = 5.59, 95% CI = 3.12-10.05, P < 0.001)
      and sedation (OR = 1.88, 95% CI = 1.19-2.98, P = 0.003), compared to control
      (local anaesthetic without fentanyl). Fentanyl had no effect on respiratory
      depression, nausea, vomiting and Apgar score. One case of respiratory depression
      of a newborn was observed. Because of the very low number of trials selected,
      evaluation of adrenaline and clonidine was not feasible. CONCLUSION: The analysis
      of current literature shows that the addition of fentanyl to local anaesthetics
      for intraoperative epidural analgesia is safe and advantageous. The reduction in
      the incidence of pain during surgery is quantitatively high and therefore
      clinically significant. Side-effects are mild. Randomized, controlled trials have
      to be performed in order to clarify the role of adrenaline and clonidine as
      epidural adjuvants for surgical analgesia.

PMID- 9773135
TI  - Prevention of nausea and vomiting with granisetron, droperidol and metoclopramide
      during and after spinal anaesthesia for caesarean section: a randomized, double
      blind, placebo-controlled trial.
AB  - BACKGROUND: Nausea and vomiting during and after spinal anaesthesia for caesarean
      section are distressing to the patient. This study was undertaken to evaluate the
      efficacy and safety of granisetron, droperidol and metoclopramide for the
      prevention of nausea and vomiting in parturients undergoing caesarean section
      under spinal anaesthesia. METHODS: In a randomized, double-blind, placebo
      controlled trial, 120 patients received granisetron 3 mg, droperidol 1.25 mg,
      metoclopramide 10 mg or placebo (saline) (n = 30 of each) i.v. immediately after
      clamping of the foetal umbilical cord. Nausea, vomiting and safety assessments
      were performed during and after spinal anaesthesia for caesarean section.
      RESULTS: The incidence of intraoperative, post-delivery nausea and vomiting was
      13%, 17%, 20% and 63% after administration of granisetron, droperidol,
      metoclopramide and placebo, respectively; the corresponding incidence during 0-3
      h after surgery was 7%, 27%, 27% and 43%; the corresponding incidence during 3-24
      h after surgery was 7%, 20%, 23% and 37% (P < 0.05; overall Fisher's exact
      probability test). No clinically important adverse events were observed in any of
      the groups. CONCLUSION: Granisetron is highly effective for preventing nausea and
      vomiting during and after spinal anaesthesia for caesarean section. Droperidol
      and metoclopramide are effective for the prevention of intraoperative, post
      delivery emesis, but are ineffective for the reduction of the incidence of
      postoperative emesis.

PMID- 9773136
TI  - Slow injection of local anaesthetic will decrease pain during dorsal penile nerve
      block.
AB  - PURPOSE: To evaluate whether a very slow injection of local anaesthetics during
      dorsal penile nerve block for circumcision causes less pain than a more rapid
      injection. METHODS: In a prospective, double-blind, randomized study, 75 patients
      aged 15 to 53 yr (mean +/- SD = 22 +/- 8.4 yr) were randomized into two groups. A
      solution of 2% lidocaine, 1 mg.kg-1, and 0.5% bupivacaine, 0.5 mg.kg-1 without
      epinephrine to a maximum dose of 10 ml was injected using either a very slow rate
      (injection time 100 to 150 s, Group A) or a faster rate (injection time 40 to 80
      s, Group B). Patients were questioned regarding pain by a physician who was
      blinded to the mode of therapy. Pain was rated as 1) mild (negligible), 2)
      moderate (non-negligible, but easily endurable), 3) intense (but endurable) and
      4) total refusal to continue. RESULTS: A significant pain score difference was
      found between Groups A and B (median = 1 vs. 2, P = 0.0006) as well as a
      significant correlation between pain score and the rate of infiltration (rs = 
      0.394, P < 0.0001). CONCLUSIONS: Slow injection is an important factor in
      reducing pain during penile block.

PMID- 9773137
TI  - The effect of i.v. enalaprilat in chronically treated hypertensive patients
      during cardiac surgery.
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors are well established
      as long-term antihypertensives and have also been proved useful in hypertensive
      emergencies. Therefore, we investigated whether intraoperative i.v. enalaprilat
      may reduce the incidence of perioperative hypertensive reactions in coronary
      artery bypass grafting (CABG). METHODS: Thirty-eight male patients chronically
      treated for arterial hypertension and scheduled for CABG randomly and double
      blindly received either enalaprilat 30 micrograms.kg-1 or NaCl 0.9% at the time
      of skin incision. Intraoperatively, increases of mean arterial pressure (MAP) >
      85 mmHg or > 80 mmHg during cardiopulmonary bypass (CPB) were treated by an
      urapidil bolus. The total intraoperative amount of urapidil was documented for
      both groups. Systemic and pulmonary hemodynamics as well as the plasma levels of
      epinephrine, norepinephrine, arginine vasopressin and renin were measured
      intraoperatively and up to 2 h after admission to the intensive care unit.
      RESULTS: Mean arterial pressure, cardiac index and systemic vascular resistance
      did not differ between the enalaprilat and the control group. Renin plasma levels
      significantly increased after infusion of enalaprilat and did not change in the
      placebo group. Catecholamine and arginine vasopressin plasma levels increased
      significantly during CPB and remained high in the postoperative period without
      any intergroup difference. The same amount of urapidil had to be given in the two
      groups to maintain MAP below the defined limit. CONCLUSION: We conclude that
      infusing 30 micrograms.kg-1 enalaprilat in patients chronically treated for
      arterial hypertension does not prevent hypertensive reactions during CABG.

PMID- 9773138
TI  - Does lidocaine protect the heart during coronary revascularisation?
AB  - BACKGROUND: Lidocaine has been used as the primary antiarrhythmic agent for
      ventricular arrhythmias during acute myocardial infarction (MI) and open heart
      surgery. Its cardioprotective effects have been studied in experimental settings
      and also during angioplastic reperfusion and coronary revascularisation. The
      basic mechanism of action, probably also involved with cardioprotection, has been
      demonstrated to be blockade of cardiac sodium channels. In this open study we
      investigated the contribution of continuous lidocaine infusion to
      cardioprotection during coronary revascularisation with blood cardioplegia.
      METHODS: During coronary revascularisation with cold blood cardioplegia, a study
      group of 50 patients received a prophylactic lidocaine infusion for 20 h started
      with a bolus dose before aortic clamping; another group of 50 patients without
      the infusion served as a control group. Serum troponin T concentration, serum
      creatine kinase MB activity and electrocardiography were the main parameters
      recorded. RESULTS: Serial measurement of Troponin T (P = 0.06) and CK-MB values:
      (P = 0.09) were slightly lower in the lidocaine group, but the differences were
      not statistically significant. CONCLUSION: Lacking statistically significant
      evidence of improved cardioprotection, lidocaine infusion cannot be recommended
      as a routine treatment during coronary revascularisation.

PMID- 9773139
TI  - Influence of dopexamine hydrochloride on haemodynamics and regulators of
      circulation in patients undergoing major abdominal surgery.
AB  - BACKGROUND: Catecholaminergic support is often used to improve haemodynamics in
      patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive
      catecholamine with beneficial microcirculatory properties. METHODS: The influence
      of perioperative administration of dopexamine on cardiorespiratory data and
      important regulators of macro- and microcirculation were studied in 30 patients
      undergoing Whipple pancreaticduodenectomy. The patients received randomized and
      blinded either 2 micrograms.kg-1.min-1 of dopexamine (n = 15) or placebo (n = 15,
      control group). The infusion was started after induction of anaesthesia and
      continued until the morning of the first postoperative day. Endothelin-1 (ET-1),
      vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels
      were measured from arterial blood samples. Measurements were carried out after
      induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h
      after surgery, and on the morning of the first postoperative day. RESULTS:
      Cardiac index (CI) increased significantly in the dopexamine group (from 2.61 +/-
      0.41 to 4.57 +/- 0.78 l.min-1.m-2) and remained elevated until the morning of the
      first postoperative day. Oxygen delivery index (DO2I) and oxygen consumption
      index (VO2I) were also significantly increased in the dopexamine group (DO2I:
      from 416 +/- 91 to 717 +/- 110 ml/m2.m2; VO2I: from 98 +/- 25 to 157 +/- 22
      ml/m2.m2), being significantly higher than in the control group. pHi remained
      stable only in the dopexamine patients, indicating adequate splanchnic perfusion.
      Vasopressive regulators of circulation increased significantly only in the
      untreated control patients (vasopressin: from 4.37 +/- 1.1 to 35.9 +/- 12.1
      pg/ml; ET-1: from 2.88 +/- 0.91 to 6.91 +/- 1.20 pg/ml). CONCLUSION: Patients
      undergoing major abdominal surgery may profit from prophylactic perioperative
      administration of dopexamine hydrochloride in the form of improved haemodynamics
      and oxygenation as well as beneficial influence on important regulators of organ
      blood flow.

PMID- 9773140
TI  - Vasopressor hormone response following mesenteric traction during major abdominal
      surgery.
AB  - BACKGROUND: We investigated the vasopressor hormone response following mesenteric
      traction (MT) with hypotension due to prostacyclin (PGI2) release in patients
      undergoing abdominal surgery with a combined general and epidural anesthesia.
      METHODS: In a prospective, randomized, placebo-controlled study we administered
      400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General
      anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5,
      15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and
      measured 6-keto-PGF1 alpha (stabile metabolite of PGI2), TXB2 (stabile metabolite
      of thromboxane A2) active renin, and arginine vasopressin (AVP) plasma
      concentrations by radioimmunoassay. Catecholamine levels were assessed by high
      pressure liquid chromatography (HPLC) with electrochemical detection. RESULTS:
      Following MT, arterial hypotension occurred along with a substantial PGI2
      release. This was completely abolished by ibuprofen administration. Although
      plasma levels of 6-keto-PGF1 alpha (1133 (708) vs. 60 (3) ng/L, median (median
      absolute deviation), P = 0.0001, placebo vs. ibuprofen) remained significantly
      elevated, blood pressure was restored within 30 min after MT in the placebo
      group. At the same point in time plasma concentrations of TXB2 (164 (87) vs. 58
      (1) ng/L, P = 0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P = 0.001), AVP (41
      +/- (18) vs. 12 (7) ng/L, P = 0.0004), and active renin (27 (12) vs. 12 (4) ng/L,
      P = 0.001) were significantly higher in placebo-treated patients. CONCLUSION:
      Under combined general and epidural anesthesia arterial hypotension following MT
      due to endogenous PGI2 release is associated with enhanced release of AVP, active
      renin, epinephrine and thromboxane A2, presumably contributing to hemodynamic
      stability within 30 min after MT.

PMID- 9773141
TI  - Haemodynamic and metabolic changes induced by repeated episodes of hypoxia in
      pigs.
AB  - BACKGROUND: Repeated hypoxia and surgical trauma trigger a potent neuroendocrine
      response and their association is thought to play a pivotal role in the
      pathogenesis of multi-organ dysfunction. We investigated the cardiovascular and
      metabolic responses to repeated acute hypoxia in anaesthetised and surgically
      instrumented pigs. METHODS: Under ketamine-midazolam anaesthesia, 15 pigs were
      surgically instrumented for measurements of cardiac output, vascular pressures
      and organ blood flows. Lactate production and O2 uptake were determined in the
      brain, liver, kidney and intestine. Ten animals were subjected to two 12-min
      periods of ventilatory hypoxia (FIO2 = 7%) followed by re-oxygenation and 5
      animals underwent 120-min normoxic ventilation (Control group). RESULTS: Both
      hypoxic challenges produced a comparable release of catecholamines that was
      associated with increased cardiac output and redistribution of blood flow away
      from the intestinal and renal areas towards the brain and the liver; O2 uptake
      was markedly reduced in the intestine (-56 +/- 10%, P < 0.05) and least affected
      in the brain and the kidney (-19 +/- 12% and -23 +/- 21%, respectively). During
      the second hypoxic test, lethal cardiovascular depression occurred in 5 animals;
      these non-survivors demonstrated impaired hyperdynamic response and incomplete
      recovery of intestinal O2 uptake during the first hypoxia/reoxygenation test. In
      the Control group, normoxic ventilation was not associated with significant
      haemodynamic and metabolic changes. CONCLUSION: Intraoperative hypoxia causes
      marked heterogeneity in organ blood flow and metabolism. The inability to develop
      a hyperdynamic cardiovascular response during a first hypoxic event, as well as a
      persistent intestinal O2 debt following re-oxygenation, predict the occurrence of
      death during the second hypoxic insult.

PMID- 9773142
TI  - Intravenous endotoxin does not increase tissue extravasation of albumin in rats.
AB  - BACKGROUND: It is unclear whether activation of the inducible nitric oxide
      synthase (iNOS) increases or decreases the extravasation of plasma. METHODS:
      Chloralose anaesthetised male Wistar rats received E. coli lipopolysaccharide
      (LPS), 3 mg kg-1 i.v., or the corresponding volume of saline, 3 or 5 h before the
      end of the experiment. Mean arterial pressure (MAP) and heart rate (HR) were
      recorded. Tissue clearance of radio-labelled albumin, during the last 2 h of each
      experiment, was determined by a double-isotope method. In separate animals, the
      serum concentration of nitrite and nitrate was determined, 5 h after LPS or the
      solvent. MAIN RESULTS: LPS initially decreased MAP and lastingly increased HR. In
      the 3-h LPS animals (n = 8), tissue plasma clearance was lower in the heart and
      calf muscle and increased only in diaphragm, compared to corresponding control
      animals (n = 8). In the 5-h LPS rats, clearance was lowered (n = 8) in the entire
      gastrointestinal tract and in testes, compared to controls (n = 8). The serum
      nitrite/nitrate concentration was higher in animals given LPS (n = 6) than in
      controls (n = 6). CONCLUSION: After LPS, tissue clearance of albumin was not
      increased in any major tissue, in spite of increased serum levels of NO end
      products. Apparently, after activation of iNOS, the augmented release of NO is
      not necessarily associated with increased albumin extravasation.

PMID- 9773143
TI  - Renal dysfunction after total knee replacement is not aggravated by bone cement.
AB  - BACKGROUND: Total knee replacement (TKR) has been associated with postoperative
      renal dysfunction. The use of monomeric methylmethacrylate (MMA) bone cement
      causes hypotension by several mechanisms. METHODS: In 30 patients undergoing TKR
      with (n = 16), or without (n = 14) bone cement, serum levels of creatinine,
      cystatin C and creatine kinase (CK) and urinary levels of creatinine and markers
      for glomerular (albumin, IgG) and tubular (protein HC) function were recorded
      preoperatively and on days 1, 2, 4 and 8 postoperatively. RESULTS: There were no
      changes in serum creatinine. Both groups had a transient, 5-fold rise in CK and a
      continuous increase in cystatin C. The urinary concentration of proteins
      increased postoperatively with a peak in the glomerular markers on day 1 and in
      the tubular marker on day 2. There were no significant differences in proteinuria
      between the groups. The 95% CIs for the difference in the means of the AUCs of
      the logarithmically transformed values for the proteins were never more than 19%.
      On day 8 all proteins had returned to their preoperative levels. CONCLUSION:
      Postoperatively, there was a transient increased leakage of proteins, indicating
      glomerular and tubular dysfunction. This was not influenced by the use of MMA
      bone cement.

PMID- 9773144
TI  - Effects of ketorolac and dextran-70 alone and in combination on haemostasis.
AB  - BACKGROUND: Dextran may be used in surgical patients for thromboprophylaxis or
      volume expansion along with ketorolac, a nonsteroidal anti-inflammatory drug, for
      analgesia. As these two agents can influence the haemostatic system at different
      sites, it is important to demonstrate that there is no adverse haemostatic
      interaction between them. METHODS: The haemostatic interaction between
      intravenous dextran-70 and intramuscular ketorolac was assessed in a double
      blind, randomised, crossover study of healthy male volunteers each given all four
      combinations of ketorolac/placebo intramuscularly and dextran/placebo
      intravenously. The effect of ketorolac and dextran on haemostasis was assessed by
      the following techniques: skin bleeding time, in vitro platelet aggregation
      function, whole blood thromboxane generation, von Willebrand factor antigen,
      factor VIII coagulant activity and tissue plasminogen activator. The results were
      analysed for the effects of ketorolac and dextran and for any evidence of an
      interaction. RESULTS: Ketorolac inhibited platelet function and thromboxane
      generation. Dextran reduced factor VIII coagulant activity. Neither agent had a
      significant effect on bleeding time, von Willebrand factor or tissue plasminogen
      activator. There was only evidence of a small but statistically significant
      interaction between ketorolac and dextran on thromboxane generation. There was no
      evidence of any other interaction of ketorolac with dextran. CONCLUSION: This
      interaction on thromboxane generation is unlikely to be of clinical significance
      as substantial inhibition of thromboxane generation occurs with ketorolac alone.

PMID- 9773145
TI  - The influence of age and administration rate on the brain sensitivity to propofol
      in rats.
AB  - BACKGROUND: It is well established that the dose of propofol for induction of
      anaesthesia is influenced by patient age. This may be explained by differences in
      pharmacokinetics or pharmacodynamics. To evaluate the effect of age on propofol
      pharmacodynamics, the brain concentration of propofol at the time of an EEG end
      point was used as a measure of CNS sensitivity. METHODS: Ninety-five rats were
      assigned to 4 groups. Anaesthesia was induced by continuous propofol infusion at
      different rates. The dose of propofol and duration of anaesthesia were determined
      from 23 up to 776 days of age. The rats were killed at 23, 287 or 776 days of age
      at the EEG end-point and samples of cerebral cortex, midbrain, cerebellum, serum
      and fat tissue were submitted to HPLC analysis of propofol concentrations.
      RESULTS: The induction dose of propofol varied with age and administration rate.
      Young animals needed a higher dose of propofol. Old animals had higher brain
      concentrations of propofol at the EEG end-point than young animals. However,
      propofol concentrations in serum were higher in young animals. The propofol
      concentration in the brain was influenced by the administration rate. CONCLUSION:
      The dose of propofol for induction of anaesthesia in rats is influenced by animal
      age and administration rate. Young animals need a larger induction dose than old
      rats, but are more sensitive as measured by the brain concentration of propofol.
      The larger induction dose in young rats when compared with adults is explained by
      pharmacokinetic differences rather than by pharmacodynamic changes.

PMID- 9773146
TI  - Volatile anaesthetics reduce adhesion of blood platelets under low-flow
      conditions in the coronary system of isolated guinea pig hearts.
AB  - BACKGROUND: Inhibitory effects of volatile anaesthetics on platelet aggregation
      have been demonstrated in several studies. However, the influence of volatile
      anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
      METHODS: Isolated hearts of guinea pigs were perfused with buffer in the absence
      or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow
      rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10
      min. Before, during and after low-flow perfusion, a bolus of human platelets was
      applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml
      human thrombin was infused during low-flow perfusion and reperfusion. The number
      of platelets sequestered to the endothelium was calculated from the difference
      between coronary in- and output of platelets. The myocardial production of
      lactate and consumption of pyruvate and coronary perfusion pressure were also
      determined. RESULTS: At a flow rate of 5 ml/min only about 3% of the applied
      platelets did not emerge from the coronary system, in any group. In contrast,
      13.1 +/- 1.2% (mean +/- SEM) of infused platelets became adherent in low-flow
      perfusion in the control group without anaesthetic. The adherence was reduced
      with each 1 MAC isoflurane (to 6.2 +/- 1.2%), sevoflurane (to 4.4 +/- 0.9%) or
      halothane (to 3.2 +/- 1.5%) (each P < 0.05 vs. control). Volatile anaesthetic,
      0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent
      in any case. Perfusion pressure and metabolic parameters were not statistically
      different between the control and the hearts exposed to anaesthetics. CONCLUSION:
      Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of
      platelets in the coronary system under reduced flow conditions. This action does
      not arise from vasodilation or inhibition of ischaemic stress.

PMID- 9773147
TI  - Mivazerol inhibits intrathecal release of glutamate evoked by halothane
      withdrawal in rats.
AB  - BACKGROUND: Mivazerol is a new and selective alpha 2-adrenergic receptor agonist
      devoid of hypotensive effects (1, 2). Previous studies have demonstrated that
      mivazerol prevents hemodynamic instability during emergence from halothane
      anesthesia in rats (3). The present study was to determine whether glutamate and
      aspartate are involved in this action of mivazerol, at the second to third
      thoracic segments (T2-T3) of the spinal cord. METHODS: In vivo microdialysis in
      combination with high-performance liquid chromatography (HPLC) was employed in
      the study. Blood pressure (BP) and heart rate (HR) were recorded along with
      intrathecal (i.t.) microdialysis perfusion. RESULTS: BP, HR and i.t. release of
      glutamate (GLU, pmol/microliter) were stable in the rats under 1.1% halothane
      anesthesia. However, halothane withdrawal immediately increased BP, HR, and i.t.
      release of GLU, and remained elevated for at least 2 h after withdrawal of
      halothane. Thirty minutes prior to halothane withdrawal, intravenous (i.v.)
      infusion of mivazerol (15 micrograms.kg-1.h-1) almost completely prevented the
      increases in HR (delta 18 +/- 7 vs delta 79 +/- 7 beats/min), and in the i.t.
      release of GLU (delta 10.3 +/- 3.7 vs delta 30.6 +/- 5.9; 112% vs 167%). Local
      i.t. microinjection of mivazerol (2.5 micrograms/kg) 2 min prior to withdrawal of
      halothane also blocked the HR responses, as well as on the i.t. release of GLU
      following halothane withdrawal. CONCLUSION: The present study demonstrates that
      emergence from halothane anesthesia increases i.t. release of GLU, and that
      mivazerol has an inhibitory effect on the above, through its direct action on the
      spinal cord.

PMID- 9773148
TI  - High thoracic/low cervical, long-term intrathecal (i.t.) infusion of bupivacaine
      alleviates "refractory" pain in patients with unstable angina pectoris. Report of
      2 cases.
AB  - BACKGROUND: There is no reliable treatment for "refractory" pain from unstable
      angina pectoris (UAP) when epidural infusion of bupivacaine has failed to relieve
      it. In two such cases we explored the potential of intrathecal (i.t.) bupivacaine
      infusion to provide pain relief. PATIENTS AND METHODS: Two female patients, 70
      and 67 years. An 18-G nylon catheter was inserted intrathecally through a 17-G
      Tuohy needle via the T2-T3 interspace and its tip located at the height of C6-C7
      vertebrae. The catheter was connected to a portable, programmable electronic pump
      filled with bupivacaine 5 mg/ml. The infusion started at rates of 0.1-0.2 ml/h,
      with optional bolus doses of 0.1-0.2 ml, 4-2 times/h, respectively, by PCA
      (Patients-Controlled Analgesia), and then adjusted to give the patients
      satisfactory (80%-100%) pain relief. RESULTS: Pain relief was obtained with doses
      of i.t.-bupivacaine ranging from 17 to 45 (mean = 25) mg/d. The pain intensity
      decreased from VAS (Visual Analogue Score) 9-10 to 0-2 out of 10. The nocturnal
      sleep improved from 2-4 to 6-7 h. The patients could now ambulate, walking or in
      a wheel-chair. The i.t.-treatment lasted 700 and 437 d, of which 540 and 343 d
      (respectively) were spent at home, and was terminated by: (a) the patient's death
      due to intracranial bleeding (1st case); (b) progressive aggravation of the
      unstable angina that could not be fully countered by increasing the bupivacaine
      dose above 1.0 mg/h due to occurrence of cerebral transient ischemic attacks,
      usually not correlated with orthostatic arterial hypotension but apparently
      facilitated by microembolization of the cerebral arteries (2nd case). CONCLUSION:
      I.t.-bupivacaine infusion may alleviate "refractory" pain in patients with
      unstable angina pectoris when epidural bupivacaine failed to do so. Its use is
      apparently limited by the IT-bupivacaine critical dosage (in these patients = 1.0
      1.5 mg/h).

PMID- 9773149
TI  - Forced hot air rewarming in hypothermic patients with cardiocirculatory arrest?

PMID- 9773150
TI  - Bilateral superficial radial artery at the wrist.

PMID- 9773151
TI  - [Endoscopic cholangiography in biliary tract diseases in HIV+ patients].
AB  - Biliary tract involvement in the course of the infection by HIV was first
      described in 1983. Since then, various opportunistic infections have been
      responsible of different biliary lesions, coming to a new entity called
      "cholangiopathy associated to HIV". Our aim was to determined the use of ERCP in
      the management of HIV patients with cholestasis. From August 1994 to October
      1997, 11 HIV patients (8 men, 3 women, mean age 35 y.) were submitted to ERCP
      because of jaundice (n = 8), upper right abdominal pain (n = 8), fever (n = 6),
      pruritus (n = 5) and elevated alkaline phosphatase (n-10). In 7 the diagnosis of
      AIDS had already be made. All had hepatobiliary ultrasound and endoscopic
      periampullar duodenal mucosa biopsy was taken in 7. According to Cello, 4 types
      of radiologic lesions were considered: 1) Papillary stenosis with dilated
      extrahepatic biliary tract. 2) Sclerosing cholangitis (focal intra or
      extrahepatic stenosis and dilatations). 3) Association of types 1 and 2.4)
      Choledocal long stenosis in the absence of previous biliary surgery or chronic
      pancreatitis. Five patients (45%) had biliary abnormalities; in 3 related to HIV
      infection: sclerosing cholangitis (n = 2) and papillary stenosis (n = 1). Two had
      choledocal stones. Four had upper right abdominal pain and dilated bile ducts at
      ultrasound. Cryptosporidium was found in duodenal mucosa in one patient with
      sclerosing cholangitis and in the patient with papillary stenosis. Biliary stents
      were placed without sphincterotomy in 2, with relief of pain and improving of
      cholestasis in only one. The choledocal stones were removed endoscopically in one
      patient and by surgery in the other. CONCLUSION: The ERCP is a useful method in
      the diagnosis and treatment of the biliary tract abnormalities associated to HIV.

PMID- 9773152
TI  - [Hepatocellular carcinoma: clinical and epidemiological characteristics].
AB  - We present 12 patients with CHC, 11 men and one woman, median age, 59.9 +/- 10.1
      cared for in two hospitals from La Plata city. The median age, the predominance
      of men and presence of cirrhosis in the 75% are similar findings to European 41%
      of the patients, consulted of the CHC has increased in our environment. The fact
      that all the patients have been symptomatic at the moment of the consultation,
      that one of them had normal liver function tests and that only two of them had
      nodule of less than 5 cm of diameter, suggest advanced stage of the disease. At
      the same time, the median of survival of 8.3 +/- 9 (DS) months post-diagnosis and
      of 3.6 +/- 8 (DS) months post surgery. 90.9% had a risk factor to undergo CHC
      (alcohol, HBC, HCV). Because of one patient, the risk of hemodyalizer patients to
      have CHC is emphasized. Therefore, it is important to prevent and treat viral
      infections. In this study, the diagnosis of the echography was of 100% and the
      histologic corroboration was done by percutaneous biopsy with ultrasound or TC
      assessment. We observed that the levels of alpha-fetoprotein had a weak, negative
      correlation, not significative, with the diameters of the nodules. Although it is
      true that the size of the sample and the retrospective character of the
      investigation inhibits us to draw definitive conclusions, the behaviour of
      alfafetoprotein creates doubts about its value in the diagnosis and screening of
      the CHC.

PMID- 9773153
TI  - [In vivo selectivity of nonsteroidal anti-inflammatory drugs on COX-1-COX-2 and
      gastrointestinal ulcers, in rats].
AB  - This work was aimed to study COX-1 and COX-2 selectivity in 16 non-steroidal anti
      inflammatory drugs (NSAIDs), at ulcerogenic doses in 2 experimental models: 1)
      provided subcutaneously (sc), after solid food(SF), (antrum ulcers and intestinal
      erosions); and 2) orally (O) (fundic and intestinal erosions). METHODS: 17 groups
      of female Wistar rats (n = 7 each group), weighing 200 g, 36 h fasting with water
      ad libitum, were submitted to the following experiments: 1. SF (Cargill chow)
      during 1 h, and then sc: 1.1 ml saline; 2. diclofenac (Di); 3. indomethacine
      (Indo); 4. Ketorolac (Ke); 5. meloxicam (Mel); 6. Pyroxicam (P); 7. tenoxicam
      (T). The dose for the aforementioned drugs was 60 mg/kg; 8. aceclofenac (Ace); 9.
      200 mg/kg nimesulide (Ni); 10. mefenamic acid (Mac); 11. aspirin (A); 12.
      etodolac (E); 13. ibuprophen (Ibu); 14. nabumetone (Na); 15. naproxene (Nap); 16.
      ketoprophen (Ket); 17. paracetamol (Pa), 500 mg/kg. II. The drugs where
      administered by orogastric tubing to the same groups of fasting animals. After 24
      h the animals were killed by ether overdose. Laparotomy was performed and the
      stomach and the small intestine was removed. The percentage of antum ulcer, and
      fundic and intestinal erosion (mm2) was tabulated by planimetry. Blood and
      histological samples were obtained. RESULTS: The NSAIDs Indo, Ibu, Ke, Ket, P and
      Te yielded an antrum ulcer area: 5-29% and intestinal erosion, 101-395 mm2,
      similar to Indo (p > 0.50). In contrast there were neither ulcers nor intestinal
      erosions with Mac, A, Di, E and Nap (p > 0.50). While there were absence of
      ulcers with Ace, Me, Na, Ni and Pa and slight intestinal erosion (0-23 mm2; p <
      0.01). II. There were differences in the following oral (NAIDs: Ace, Me, NA, Ni
      and Pa, yielding 0-5% fundic erosion and 0-22 mm2 intestinal erosion (p < 0.001).
      The other NSADs yielded 33-90% fundic erosion and 116-550 mm2 intestinal erosion,
      similarly to Indo (p > 0.50). HISTOLOGY: Leukocyte infiltrate in the
      gastrointestinal mucosa with all the NSADs, except Ibu and Pa. There was also
      neutrophilia (5000-20,000), but not with Ibu and Pa (700-1200). CONCLUSIONS: COX
      2-COX-1 selectivity was demonstrated "in vivo" in aceclofenac, meloxicam,
      nabumetone, nimesulide and paracetamol.

PMID- 9773154
TI  - [Intestinal bleeding associated with systemic amyloidosis].
AB  - We report a 42-year-old man with abdominal pain, weight loss and massive
      intestinal hemorrhage that caused death. The small bowel showed massive
      infiltration with amyloid.

PMID- 9773155
TI  - [Anti-actin antibodies in acute viral hepatitis A in children].
AB  - Hepatitis A Virus (HAV) infection has been proposed as a possible trigger of
      autoimmune hepatitis type I. We have previously reported the presence of anti
      actin antibodies en protracted hepatitis A. At present the presence of anti-actin
      antibodies in acute uncomplicated hepatitis A is unknown. The aim of this study
      was to evaluate the incidence and persistence of anti-actin antibodies un
      children with acute hepatitis A. MATERIALS AND METHODS: 38 patients, 21 female
      and 17 male, with mean age of 6.5 years (range 2-13 years) were included. All
      patients were anti HAV IgM positive. The patients were clinically controlled and
      laboratory determinations such as ALT/AST, gammaglobulin, gamma GT, nuclear,
      smooth muscle (anti-actin specificity) and liver-kidney-microsome type I (anti
      LKM) antibodies, were evaluated at admission and at the first, third and fifth
      month. Anti-actin antibodies were determined by indirect immunofluorescense (IIF)
      on rat kidney, stomach and liver sections and also on monolayers of cultured
      fibroblasts. Titers higher than 1/40 were considered positive. RESULTS: 18
      patients (47.3%) were anti-actin positive in the first determination (titers 1/40
      and 1/80). In 4 patients (12.9%) these antibodies remained positive up to one
      month. All patients were negative 5 months after the onset of illness. ANA and
      anti-LKM were negative in all cases. CONCLUSIONS: 1) This data demonstrate the
      presence of anti-actin antibodies in children with uncomplicated HAV hepatitis.
      2) The antibodies remained positive for a short period of time. 3) Titers were
      lower than in autoimmune hepatitis type I. 4) Taken together these results
      suggest that anti-actin antibodies would be an expression of non specific
      stimulation of lymphocyte B.

PMID- 9773156
TI  - [HCV and HBV prevalence in hemodialyzed pediatric patients. Multicenter study].
AB  - Hemodialized pediatric patients are a risk population for the hepatitis B and C
      virus infection. The aim of this paper was to study the serum prevalence of HBV
      and HCV infection in hemodialized children. We study 61 pediatric patients at
      hemodialisis, 12 on renal transplant, range between 2 and 20 years old (mean:
      12.9 years), 23 male and 38 female. The specific anti-HCV IgC were measured by
      enzyme immunoassay (ELISA Abbott) and confirmed by LIA-TEK (Organon). The anti
      HBV were measured by ELISA Abbott and transaminases by cinetic method (ASAT: 29
      UI/L and ALT: 33 UI/L). The 19.7% of studied children were HCV (+) and 29.5% were
      HBV (+), 38.9% of them were HbsAg (+) and 50% anti-HBs (+). The HCV and HBV
      infection was more elevated in relation to the transfusion number and the
      hemodilisis time. The elevation of ALT/ASAT activity isn't a right infection
      index for HCV and HBV in this children.

PMID- 9773158
TI  - [Endoscopic cholangiography in HIV+ patient. A clinical approach].

PMID- 9773157
TI  - [Endoscopic cholangiography in an HIV+ patient. A cholangiographic approach].

PMID- 9773159
TI  - [Hepatocellular carcinoma, a malignant tumor diagnosed with more frequency].

PMID- 9773160
TI  - Kidney transplant: changing the filter.

PMID- 9773161
TI  - Reducing cumulative lifetime disability: the compression of morbidity.

PMID- 9773162
TI  - Exercise and sport after organ transplantation.

PMID- 9773163
TI  - The "Hoddle Muddle": using faith healers and other complementary therapists in
      sports medicine.

PMID- 9773164
TI  - Dancing through adolescence.

PMID- 9773166
TI  - Where is the crowd doctor?

PMID- 9773165
TI  - Eye injuries in sport: where next?

PMID- 9773168
TI  - Does post-exercise massage treatment reduce delayed onset muscle soreness? A
      systematic review.
AB  - BACKGROUND: Delayed onset muscle soreness (DOMS) is a frequent problem after
      unaccustomed exercise. No universally accepted treatment exists. Massage therapy
      is often recommended for this condition but uncertainty exists about its
      effectiveness. AIM: To determine whether post-exercise massage alleviates the
      symptoms of DOMS after a bout of strenuous exercise. METHOD: Various computerised
      literature searches were carried out and located seven controlled trials.
      RESULTS: Most of the trials were burdened with serious methodological flaws, and
      their results are far from uniform. However, most suggest that post-exercise
      massage may alleviate symptoms of DOMS. CONCLUSIONS: Massage therapy may be a
      promising treatment for DOMS. Definitive studies are warranted.

PMID- 9773167
TI  - Determinants and control of breathing during muscular exercise.

PMID- 9773169
TI  - Comparison of different techniques to measure body composition in moderately
      active adolescents.
AB  - OBJECTIVE: To evaluate the differences in the estimate of body fat percentage
      (%FM) and the amount (kg) of fat free mass (FFM) by different methods in 26
      moderately active adolescents very similar in age, body fatness, and training
      status. METHODS: Mean (SD) age was 16.7 (0.9) years, height was 177.0 (5.1) cm,
      and weight 68.0 (5.2) kg. %FM was assessed using dual-energy x ray absorptiometry
      (DXA) and two skinfold prediction equations: that of Slaughter et al (%FM Sla)
      and that of Deurenberg et al (%FM Deu). In the same way, FFM was measured using
      DXA and different impedance equations: those of Suprasongsin et al (FFM Sup),
      Schaefer et al (FFM Sch), Houtkooper et al (FFM Hou), and Deurenberg et al (FFM
      Deu). To determine the interchangeability of the different methods of measuring
      %FM and FFM, one way analysis of variance, standard error (SE), and coefficient
      of variation (CV%) ((SD/mean) x 100) were used. RESULTS: On average, no
      significant statistical differences were observed between the values determined
      for %FM: DXA value, 11.7 (5.4%); %FM Sla, 10.9 (4.0)%; %FM Deu, 11.5 (2.3)%. On
      the other hand, SE and CV% between each pair of the three methods used showed
      very large variability. With regard to the measurement or prediction of FFM, the
      mean value measured by DXA was significantly higher than that predicted by the
      equation of Sch (+7.2 kg, p < 0.001), Deu (+3.2 kg, p < 0.001), and Hou (+2.6 kg,
      p < 0.001), whereas it was lower than that predicted by the equation of Sup (-1.6
      kg, p < 0.05). The Hou and Deu values were the only two that, on average, did not
      differ in a statistically significant way, although they showed the highest CV%.
      CONCLUSIONS: In our sample of moderately active adolescents the estimated values
      for %FM and FFM appear to be highly dependent on method.

PMID- 9773170
TI  - Sport and active recreation injuries in Australia: evidence from emergency
      department presentations.
AB  - OBJECTIVE: Despite the rise in specialist clinical services for the management of
      sports and active recreation injury, many patients attend hospital emergency
      departments for treatment. The purpose of this study was to describe sports
      injury cases presented to selected hospital emergency departments around
      Australia for the period 1989-1993. METHODS: Routinely collected emergency
      department injury presentation data from the Australian National Injury
      Surveillance Unit were examined. Data on 98,040 sports and active recreation
      emergency department presentations were analysed. Sports and active recreation
      activities were ranked according to frequency of presentation. Relative
      proportions of injury type and body region injured were determined. Data are
      presented separately for children (<15 years of age) and adults (>15 years of
      age). RESULTS: Among the 10 activities that most commonly led to a sports or
      active recreation injury presentation for all ages were cycling, Australian
      football, basketball, soccer, cricket, netball, and rugby. For children, injuries
      were also commonly associated with roller skating/blading, skateboarding, and
      trampolining. Hockey, martial arts, and dancing injuries were frequent in adults.
      Most sporting injuries occurred during organised competition or practice whereas
      the active recreation injuries occurred in a variety of settings. Fractures,
      strains, and sprains, particularly to the lower and upper extremities, were
      common types of injury. CONCLUSION: The rich, but nevertheless limited,
      information available about sports and active recreation injuries from data
      collected in emergency departments indicates that these activities are a common
      context for injury at the community level in Australia.

PMID- 9773171
TI  - Glenohumeral joint: internal and external rotation range of motion in javelin
      throwers.
AB  - OBJECTIVE: To assess differences in glenohumeral joint rotatory range of movement
      in javelin throwers between the throwing and non-throwing arm. METHOD: A
      universal 360 degrees goniometer was used to assess glenohumeral joint external
      and internal rotation range in 90 degrees of shoulder abduction in a group of ten
      senior international javelin throwers. RESULTS: Both arms had significantly
      greater degrees of external than internal rotation (p < 0.01), and the throwing
      arm had significantly greater range of external rotation than the non-throwing
      arm (p < 0.01). CONCLUSIONS: The presence of an excessive range of external
      rotation in the throwing shoulder has the potential to increase eccentric load on
      the rotator cuff muscles and strain on the passive restraints of the glenohumeral
      joint. Both of these factors have been implicated in the pathological processes
      leading to injury in the overhead throwing athlete.

PMID- 9773172
TI  - Cognitive orientations in marathon running and "hitting the wall".
AB  - OBJECTIVES: To investigate whether runners' cognitions during a marathon are
      related to "hitting the wall". To test a new and more comprehensive system for
      classifying cognition of marathon runners. METHODS: Non-elite runners (n = 66)
      completed a questionnaire after finishing the 1996 London marathon. The runners
      were recruited through the charity SPARKS for whom they were raising money by
      running in the race. RESULTS: Most runners reported that during the race their
      thoughts were internally associative, with internally dissociative thoughts being
      the least prevalent. Runners who "hit the wall" used more internal dissociation
      than other runners, indicating that it is a hazardous strategy, probably because
      sensory feedback is blocked. However, internal association was related to an
      earlier onset of "the wall", suggesting that too much attention on physical
      symptoms may magnify them, thereby exaggerating any discomfort. External
      dissociation was related to a later onset, probably because it may provide a
      degree of distraction but keeps attention on the race. CONCLUSIONS: "Hitting the
      wall" for recreational non-elite marathon runners is associated with their
      thought patterns during the race. In particular, "the wall" is associated with
      internal dissociation.

PMID- 9773173
TI  - Ticks: danger lurking in the long grass.

PMID- 9773174
TI  - Cost-effectiveness of a primary care based physical activity intervention in 45
      74 year old men and women: a randomised controlled trial.
AB  - OBJECTIVE: To assess the cost-effectiveness of a primary care based intervention
      aimed at increasing levels of physical activity in inactive people aged 45-74.
      METHODS: A total of 714 inactive people aged 45-74, taken from two west London
      general practices, were randomised into two groups. Intervention subjects were
      invited to a consultation with an exercise development officer, and offered a
      personalised 10 week programme to increase their level of regular physical
      activity, combining leisure centre and home based activities. Control subjects
      were sent information on local leisure centres. All subjects were followed up at
      eight months. RESULTS: There was a net 10.6% (95% confidence interval 4.5 to
      16.9%) reduction in the proportion of people classified as sedentary in the
      intervention group compared with the control group, eight months after the
      intervention. The intervention group also reported an increase in the mean number
      of episodes of physical activity per week, as compared with the control group (an
      additional 1.52 episodes (95% confidence interval 1.14 to 1.95)). The cost of
      moving a person out of the sedentary group was shown to be less than 650 Pounds.
      The cost of moving someone to the now commonly recommended level was estimated at
      almost 2500 Pounds. CONCLUSIONS: Moderate physical activity can be successfully
      encouraged in previously sedentary men and women aged 45-74 through a primary
      care based intervention. The process of recruitment was the most important
      variable cost. A high uptake rate would maximise cost-effectiveness, and
      sensitivity analysis suggests that unit costs could be halved with a more
      effective recruitment strategy.

PMID- 9773175
TI  - Barriers to physical activity promotion by general practitioners and practice
      nurses.
AB  - OBJECTIVE: To examine the promotion of physical activity by general practitioners
      (GPs) and practice nurses (PNs). METHODS: A questionnaire that examined the types
      of barriers and the levels of their influence as well as stage of change for
      activity promotion and for personal behaviour was mailed to 846 subjects.
      RESULTS: The return rate exceeded 70% in each group with a high proportion (69%)
      of GPs and PNs reporting that they regularly promote physical activity with their
      patients. GPs were less likely to regularly promote physical activity with their
      patients if they indicated lack of time as a barrier (odds ratio (OR) = 0.73, 95%
      confidence interval (CI) 0.58 to 0.93) or lack of incentives (OR = 0.74, 95% CI
      0.59 to 0.94), and more likely to promote exercise if they themselves were
      regular exercisers (OR = 3.19, 95% CI 1.96 to 5.18). However, for PNs longer
      consultation times (by 1.5 to 2 minutes) had a higher likelihood of producing
      regular promotion of activity (OR = 1.61, 95% CI 1.02 to 1.62). For PNs personal
      physical activity stage was the strongest significant predictor of promotion
      level, but with a stronger effect (OR = 4.77, 95% CI 1.48 to 15.35) than in the
      GPs. CONCLUSION: The main finding is that GPs in the action or maintenance stage
      of changing their own physical activity are three times more likely to regularly
      promote the same behaviour in their patients than those in the other stages; for
      PNs the same difference quadruples the likelihood of them promoting physical
      activity. Professional readiness to change is influenced by known system barriers
      in GPs, and not in PNs, but is more strongly predicted by personal physical
      activity behaviour in both groups.

PMID- 9773176
TI  - Effect of a carbohydrate-electrolyte drink on endurance capacity during prolonged
      intermittent high intensity running.
AB  - OBJECTIVE: To examine the effect of a carbohydrate-electrolyte solution on
      endurance capacity during prolonged intermittent running. METHODS: Nine subjects
      (eight men and one woman) ran to exhaustion on a motorised treadmill on two
      occasions separated by at least 10 days. After an overnight fast, they performed
      repeated 15 second bouts of fast running (at 80% Vo2MAX for the first 60 minutes,
      at 85% Vo2MAX from 60 to 100 minutes of exercise, and finally at 90% Vo2MAX from
      100 minutes of exercise until exhaustion), separated by 10 seconds of slow
      running (at 45% Vo2MAX). On each occasion they drank either a water placebo (P)
      or a 6.9% carbohydrate-electrolyte (CHO) solution immediately before the run (3
      ml/kg body mass) and every 20 minutes thereafter (2 ml/kg body mass). RESULTS:
      Performance times were not different between the two trials (112.5 (23.3) and
      110.2 (21.4) min for the P and CHO trials respectively; mean (SD)). Blood glucose
      concentration was higher in the CHO trial only at 40 minutes of exercise (4.5
      (0.6) v 3.9 (0.3) mmol/1 for the CHO and P trials respectively; p < 0.05), but
      there was no difference in the total carbohydrate oxidation rates between trials.
      CONCLUSION: These results suggest that drinking a 6.9% carbohydrate-electrolyte
      solution during repeated bouts of submaximal intermittent high intensity running
      does not delay the onset of fatigue.

PMID- 9773177
TI  - Rectus abdominis rhabdomyolysis after sit ups: unexpected detection by bone scan.
AB  - Uptake of technetium-99m methylene diphosphonate by the rectus abdominis muscle
      was unexpectedly found in a 29 year old man who had started to perform 30 to 40
      sit ups a day for five days before the bone scan. After a week of rest, serum
      creatine kinase activity was still abnormal but muscle uptake of technetium-99m
      methylene diphosphonate had ceased. This specific muscle injury after short term
      sit ups as well as the resolution of the phenomenon within a week are of
      interest.

PMID- 9773178
TI  - Displaced avulsion of the ischial apophysis: a hamstring injury requiring
      internal fixation.
AB  - A case is reported of an adolescent sprinter who was chronically disabled by pain
      after non-operative management for an acute hamstring injury. He had sustained an
      avulsion fracture of the ischial apophysis with displacement of 2.5 cm. Avulsion
      fractures of the ischial apophysis with displacement of 2 cm or more are unusual,
      but they frequently result in a symptomatic non-union, and early diagnosis, open
      reduction, and internal fixation is to be encouraged.

PMID- 9773179
TI  - Iatrogenic acute hyponatraemia in a college athlete.
AB  - Hyponatraemia is one of the most common electrolyte abnormalities, leading to
      significant morbidity and mortality. In the most basic sense, hyponatraemia can
      be due to sodium loss or fluid excess. The extracellular fluid status is used to
      clinically divide hyponatraemia into three categories to help to determine both
      the cause and treatment required. Hyponatraemic patients can be categorised on
      the basis of their fluid status as hypovolaemic, euvolaemic, or hypervolaemic.
      Another distinction to make in evaluating hyponatraemia is whether the onset was
      acute or chronic in nature. The case presented here is iatrogenic acute
      hypervolaemic hyponatraemia in a college athlete. The patient presented in
      respiratory distress with an altered mental status after the administration of
      hypotonic fluids for treatment of muscle cramps. Treatment included intubation,
      water restriction, and furosemide, to which he responded favourably.
      Hyponatraemia should be in the differential diagnosis for patients presenting
      after intravenous fluid administration.

PMID- 9773180
TI  - Sensitivity of reticulocyte indices to iron therapy in an intensely training
      athlete.
AB  - Iron deficiency anaemia, and its debilitating effect on performance, is an area
      of concern for many female athletes. Automated technologies that analyse
      individual reticulocytes may provide a sensitive measure of bone marrow response
      to iron supplementation. The reticulocyte characteristics of a female volleyball
      player with frank iron deficiency anaemia, and her subsequent response to oral
      iron therapy, are reported.

PMID- 9773181
TI  - Paleo-bioenergetics: the metabolic rate of marching Roman legionaries.

PMID- 9773182
TI  - Three miles high and one hundred miles from the nearest road.

PMID- 9773183
TI  - Deceptive advertising of athletic footwear.

PMID- 9773184
TI  - Intravenous versus oral rehydration.

PMID- 9773185
TI  - Anterior cruciate ligament injury.

PMID- 9773186
TI  - Are "spontaneous" Achilles tendon ruptures truly spontaneous?

PMID- 9773187
TI  - Achilles tendinitis and ruptures.

PMID- 9773188
TI  - Plasma amino acid patterns in elite athletes.

PMID- 9773190
TI  - [Imported malaria in Tunisia].
AB  - Thanks to the national programme of malaria eradication carried out between 1968
      and 1972, there has been no active transmission of the parasitosis in Tunisia
      since the last indigenous case in 1979. Since 1980, with the increase in
      international exchanges especially with sub-Saharian countries, only imported
      cases of malaria have been reported in Tunisia. A retrospective and thorough
      survey of malaria cases diagnosed in the laboratory of parasitology of the
      Pasteur Institute in Tunis from 1980 to 1995 determined the epidemiological
      characteristics of this imported parasitosis. All in all, during the sixteen
      years following eradication, 245 cases were registered. The majority of cases
      (86.2%) was diagnosed by a systematic control of groups at risk within the
      national programme of malaria eradication. The remaining 13.8% cases sought
      medical advice when clinical symptoms appeared after their return from endemic
      countries. The population most affected by imported malaria were men (sex-ratio:
      6.8) aged between 20 and 40 years (76% of cases); 38% were Tunisians having
      sojourned in an endemic country, essentially students from sub-Saharian Africa.
      The presumed country of contamination was African in 92.7% of the cases. Entrance
      into Tunisia by patients was mainly by air; 4% of the registered cases had come
      by land from Algeria. Sound knowledge of the epidemiological characteristics of
      imported malaria would make for a better follow-up of the affected population and
      thus reduce the probability of repeated transmission.

PMID- 9773189
TI  - [Resistance of mycobacterial tuberculosis complex to the main antibacillary agent
      in Yaounde, Cameroon].
AB  - To evaluate the current prevalence of initial and acquired resistance to the main
      antituberculosis drugs in Yaounde, isolates of M. tuberculosis complex obtained
      from sputum cultures of 602 adult patients with pulmonary tuberculosis (516 new
      cases and 86 old cases) consecutively admitted into the tuberculosis centre of
      Hopital JAMOT from July 1994 to December 1995 were studied. The susceptibility of
      isolates to the major antituberculosis drugs was tested by the indirect
      proportion method. The overall resistance rate (1 or more drugs) was 35.2%, with
      initial resistance 31.8% (164 of 516) and acquired resistance 55.8% (48 of 86).
      Initial resistance to streptomycin was the most frequent (20.5%), followed by
      isoniazid 12.4%), thiacetazone (5.6%), rifampicine (0.8%) and ethambutol (0.4%).
      Initial resistance was noted as 25% to 1 drug, 5.8% to 2 drugs, 0.8% to 3 drugs
      and 0.2% to 4 drugs. Acquired resistance to isoniazid was the most frequent
      (45.3%), followed by streptomycin (40.7%), rifampicine (30.2%), thiacetazone
      (10.5%) and ethambutol (9.3%). Acquired resistance was found as 13.9% to one
      drug, 19.8% to 2 drugs, 12.8% to 3 drugs and 9.3% to 4 drugs. A combined
      resistance to rifampicine and isoniazid in the same patient was noted in 0.8% of
      the new cases and in 26.7% of the old cases. These high rates af antituberculosis
      drug resistance in Yaounde underline the urgent need to reestablish a
      tuberculosis control programme in Cameroon.

PMID- 9773191
TI  - [Malaria in the southern sanitary district of Dakar (Senegal). 1. Parasitemia and
      malarial attacks].
AB  - A survey of endemic malaria in Dakar was carried out in the southern sanitary
      district covering the city centre and neighbouring areas. The survey was
      scheduled from June 1994 to May 1995 in 12 sites distant from each other by 1000
      to 1500 meters. Clinical and parasitological data were collected during weekly
      medical follow-ups at the patients' home with the systematic research of
      Plasmodium once a month. The study included 2,337 persons aged between 1 month
      and 88 years and belonging to 284 volunteer resident families. Through monthly
      parasitological examinations, a parasite rate (P.R.) of 0.3% and a gametocyte
      rate (G.R.) of 0.005% were recorded. Only Plasmodium falciparum was observed. The
      P.R. varied according to age: from 0.1% in the children under 2 years to 0.7% in
      the young adults (15-20 years) who appeared significantly more affected than the
      other age groups, including that of children from 2 to 9 years, of whom only 0.3%
      were infected by the parasite. The P.R. varied also according to the site
      surveyed: from 0% in the city centre to 1.3% at the periphery of the sanitary
      district and according to the time of year, reaching its height of 0.8%, between
      October and December, that is just after the rainy season. At the end of the year
      of survey, 929 among those surveyed were considered to have been satisfactorily
      followed. Their annual incidence rate was 2.4% for the parasitemia and of 1.5%
      for the malaria attacks. None of the participants aged under 2 years had the
      parasite. Among the others, the annual incidence rate varied according to the age
      -although not significantly--passing from 1.1% to 5.3% for parasitemia and from
      0.4% to 3.0% for malaria attacks. Theses rates did not differ significantly
      according to site; the cases registered varied between 1% and 8% for parasitemia
      and 1% and 5.8% for malaria attacks. Only 10.6% of febrile subjects suffered from
      malaria attacks, but this rate seemed to go up between October to December,
      rising to 26.6% which corresponds to 1 case of malaria attacks for 4 cases of
      hyperthermia in that period. Weak density of Anopheline population and
      satisfactory medical surveillance explain the recorded results.

PMID- 9773192
TI  - [The microwave oven for drying thick blood smears. Benefits and limits for
      microscopic observation of Plasmodium falciparum trophozoites and gametocytes].
AB  - The micro-wave oven permits a rapid drying of thick blood smears classically used
      for parasitological malaria diagnosis. In order to evaluate this type of drying
      on the microscopic reading, a study was carried out in an hyperendemic area of
      malaria with 382 asymptomatic volunteers of all ages. Two thick smears were made
      for each volunteer, one immediately dried with a micro-wave oven for one minute,
      the second dried in the open air without any intervention. A single microscopist
      examined all the thick smears. The observation of Plasmodium falciparum
      trophozoites differed significantly between the two methods, the prevalence was
      50% by normal drying versus 41% by the micro-wave oven. The geometric mean of the
      trophozoite number for positive thick smears was significantly lower with the
      micro-wave oven. When the parasitological density with normal drying was lower
      than 200 trophozoites/microliter of blood, 54% of results were wrongly negative
      with the micro-wave oven. On the other hand, the observation of P. falciparum
      gametocytes was significantly facilitated after drying with the micro-wave oven;
      the prevalence was 8% with normal drying versus 12% by micro-wave oven. In
      conclusion, the use of the micro-wave oven for the drying of thick smears is not
      recommended for malaria diagnosis although it improves the observation and
      counting of P. falciparum gametocytes.

PMID- 9773193
TI  - [Human parasitoses in Burkina Faso. Histopathologic approach].
AB  - The aim of this first study was to assess parasitic diseases encountered in
      histological practice in Burkina Faso. An examination of 3410 pathological
      specimens showed 138 cases of parasitic diseases which represented 4% of the
      results observed for 5 years in the laboratory of YALGADO OUEDRAOGO National
      Hospital. The parasitic diseases diagnosed were in decreasing order
      Schistosomiasis 53.6%, Cysticercosis 13.1%, Mycetoma 12.3%, Cutaneous
      Leishmaniasis 8%, Amebiasis 6.6%, Filariasis 4.3%, and Histoplasmosis 2.1%. We
      recommend better data collection for integration of these diseases into the
      health policy of Burkina.

PMID- 9773194
TI  - [Schistosomiasis of the female genital tract: anatomoclinical and
      histopathological aspects. Apropos of 26 cases].
AB  - The authors report 26 cases of female genital schistosomiasis. This parasitosis
      is observed in women of ages ranging between 17 and 70 years (mean age = 30
      years) and associated with sterility (6 cases), uterine tract cancer (1 case),
      tubular pregnancy (1 case), benign teratoma (1 case) and serous cystadenoma (1
      case). The diagnosis is based on an histological analysis which shows several
      lesions with schistosomiasis (Schistosoma haematobium) eggs, confirmed by ZIEHL
      coloration. When coupled with infections these anatomical lesions lead to
      dysfunctions such as sterility and extra-uterine pregnancy through tubular
      dysfunction.

PMID- 9773196
TI  - [Gabonese thyroid pathology in a hospital milieu in Libreville: 137 cases].
AB  - From November 1991 to December 1996, 158 patients of whom 137 were Gabonese were
      examined at the Hospital Center of Libreville (department of internal medicine
      "B") for a thyroid disorder. The retrospective analysis of their files showed a
      large majority of women (94.2%) and the main diseases were euthyroidgoiter
      (54.7%), Graves'disease(13.1%), hypothyroidism (8.8%), thyroiditis (6.6%), toxic
      multinodular goiter (6.6%) while about 10% of goiters remained unclassified.

PMID- 9773195
TI  - [Complementary data on the development of intestinal parasitosis prevalence in
      Martinique].
AB  - A comparison by stool examination of the prevalence of the most common digestive
      parasitic diseases was made between the years 1968, 1972 (results from the former
      Pasteur Institute of Martinique) and 1995 (results from the Departmental
      Laboratory of Hygiene of Martinique). This study shows that the outstanding
      characteristic of the dramatic decrease in the prevalence of soil-transmitted
      helminthiasis and intestinal schistosomiasis can be noted as early as the
      beginning of the seventies. An hypothesis of explanation would point to the
      combination of a general improvement in hygiene (due to economic growth) and an
      increase in drug use given the availability of efficient and well-tolerated
      anthelmintics, and for intestinal schistosomiasis, the impact of urbanization
      along with the growing scarcity of the intermediate host snail, especially as of
      1983 thanks to an ecological control programme.

PMID- 9773197
TI  - [Radiographic aspects osteoarticular complications in Buruli ulcers].
AB  - The authors examine radiographic aspects of osteo-articular and soft tissue
      lesions on the basis of 30 files of in-patients suffering from Buruli ulcers.
      They specify the chronology and precociousness of certain signs: soft tissue
      lesions, bone demineralization, periostal apposition two months after the
      beginning of signs, and later osteolysis and joint complications. These lesions
      are not specific and occur contiguously to soft tissue lesions. The authors
      specify the part of secondary-infection germs in the appearance of bone lesions.

PMID- 9773198
TI  - [Apropos of 1 case of anisakiasis contracted in Sicily].
AB  - The authors describe a case of anisakiasis in Sicily. The diagnosis was based on
      the knowledge that a contaminated fish, Lepidopus caudatus, had probably been
      absorbed, as well as on clinical intestinal symptoms, intestinal lesions observed
      by endoscopy and O.G.D.S, duodenal infiltration by eosinophilic
      polymorphonuclear, positive ELISA anisakis serology and successful treatment by
      albendazole.

PMID- 9773199
TI  - [Bourneville's tuberous sclerosis and childhood epilepsy Apropos of 4 cases in
      Togo].
AB  - The authors report four cases of childhood epilepsy symptomatic of tuberous
      sclerosis. Epilepsy appeared in the forefront of the epileptic scene: in two
      cases, the features of epilepsy were haut mal and in two cases, WEST'S syndrome.
      Epileptic seizures began precociously for all children. Mental retardation was
      identified in three cases with one case of autistic behaviour. Diagnosis was
      possible given skin lesions, family investigations, and X-ray of the skull. Brain
      scanners were not carried out on any of the children. Whilst recognizing the
      scarcity of BOURNEVILLE'S tuberous sclerosis, the authors point out the need for
      interdisciplinary collaboration in the diagnosis of rare but not exceptional
      hereditary affections.

PMID- 9773200
TI  - [Markers of lipid peroxidation, inflammatory proteins and plasma tocopherols in
      homozygotic and heterozygotic sickle cell anemia].
AB  - Lipoperoxidation final products represented by the TBARS (substances reacting
      with the Thiobarbituric acid), inflammatory reaction proteins and sera tocopherol
      have been studied in homozygous forms as well as in heterozygous forms of sickle
      cell diseases. The significant increase of TBARS (P < 0.001) measured by
      spectrofluorimetry, the considerable decrease of the sera alpha gamma tocopherol,
      measured by HPLC (P < 0.005) in all sickle cell patients, especially in crisis
      homozygous form, reinforce our previous study (22, 23, 24). The absence of links
      between the TBARS and the tocopherols (fig. 1) suggests that other defence
      mechanisms occur without vitamin E. The collapse of haptoglobinemia in homozygous
      sickle cell patients associated with the fall of hemoglobinemia indicates a
      severe tissue and intravascular hemolysis as a consequence of LPO. Furthermore,
      the simultaneous decrease of cholesterolemia seems to indicate important
      lipoperoxide activity detected in sickle cell patients.

PMID- 9773201
TI  - [Laboratory diagnosis of monoclonal gammopathies. Prospective study of 14 cases
      in Dakar, Senegal].
AB  - Monoclonal gammapathies are detected because of clinical symptoms and biological
      tests confirm their presence. Wishing to investigate these diseases, we carried
      out a series of biochemical tests on 14 patients from October 1995 to July 1996:
      protein, cryoglobulin, electrophoresis of proteins, proteinuria of BENCE JONES, C
      reactive protein, weight measuring of immunoglobulins (Ig), immunofixation of Ig,
      creatinine and calcium. The results we obtained confirmed the presence of 14
      cases of myeloma with: -9 IgG myelomas with 6 kappa light chains and 3 lambda
      light chains -4 IgA myelomas with 2 kappa light chains and 2 lambda light chains 
      1 IgG kappa, Ig lambda biclonal gammapathy united to a cryoglobulin of class I.
      We observed a predominance of the IgG over the others Ig and the kappa over the
      alpha light chains. The proteinuria of BENCE JONES was present among 3 patients,
      hypercalcemia among 4 patients and hypercreatininemia in 1 patient with chronic
      renal failure.

PMID- 9773202
TI  - [Hepatitis B virus infection in the school milieu of Kiffa and Selibaby,
      Mauritania].
AB  - Our survey was concerned with searching for different markers of Hepatitis B
      virus infection in 267 primary and secondary school children in two Mauritanian
      sites in the south and south-east of the country. The results showed that for the
      surveyed subjects, 16.8% were carriers of HBs antigen, 21% of anti-HBs
      antibodies, 50.2% of anti-HBc antibodies and 45.4% of anti-HBe antibodies.
      Furthermore, 28.9% of the carriers of HBs antigen were also of HBe antigen. In
      all, 32.2% of the subjects had not been exposed to the Hepatitis B virus. These
      results confirmed the serious problem posed to public health by Hepatitis B
      infection and should prompt a programme to combat it.

PMID- 9773204
TI  - [Apropos of the 1997 Lasker Award].

PMID- 9773203
TI  - [Toxoplasmosis in Dakar. Seroepidemiologic sampling of 353 women of reproductive
      age].
AB  - Thanks to a serological survey carried out in Dakar from January to November 1993
      among 353 procreative women, immune cover regarding toxoplasmosis was assessed
      using ELISA methodology: 40.2% of the surveyed population had antibodies of
      toxoplasmosis. No evidence of age, pregnancy, number of previous pregnancies was
      noted in antitoxoplasmosis antibodies prevalence. The seroconversion risk seems
      to be low even when it has existed during pregnancy. Contamination occurred
      during childhood. Some sanitary education should be provided to the procreative
      population in order to achieve a better compliance with basic hygiene regulations
      during pregnancy.

PMID- 9773205
TI  - [Histopathology of Anopheles gambiae s.l. Giles, 1902 (Diptera, Culicidae)
      subjected to the larvicidal activity of the aqueous extract of Persea americana
      Miller, 1768 (Lauraceae)].
AB  - Larvae of Anopheles gambiae treated with an aqueous extract of Persea americana
      suffer important damages of the midgut. The first epithelial cells to be affected
      are those at the posterior part of the midgut which become hypertrophic after
      only 30 min. After one hour most of the cells in this part lyse. The cytoplasmic
      material is then rejected towards the lumen gut, between the peritrophic membrane
      and the midgut epithelium. Subsequently, an almost total cell degeneration is
      observed. Cells of gastric caeca and cells at the intermediary and anterior parts
      of the midgut undergo the same histopathology, albeit after a longer period.

PMID- 9773206
TI  - [Feeding preferences of malaria vectors in the city of Bouake and in the
      surrounding villages of Cote d'Ivoire].
AB  - A study of the bloodfeeding behaviour of An. gambiae and An. funestus was carried
      out in the city of Bouake and surrounding villages. The results showed that 99.4%
      of An. gambiae in the city feed on human hosts. In villages, 98.8% of An. gambiae
      and all An. funestus feed on human hosts. In this area, the anthropophily of
      major malaria vectors is almost exclusive.

PMID- 9773207
TI  - [Malaria in the southern sanitary district of Dakar (Senegal). 2. Entomologic
      data].
AB  - To complete a parasitological survey, entomological prospections were carried out
      in the southern sanitary District of Dakar, the most urbanized of the city and
      which includes the city centre and the oldest administrative districts. The
      prospections took place between June 1994 and May 1995 in sites 1.5 km apart, and
      distributed in such a manner that they covered the entire area. On a monthly
      basis, female Culicidae were collected in each site at night on human volunteers,
      followed the next day by the collection of early morning residual fauna in 10
      bedrooms located in district concessions. For a total of 308 collections at night
      on human volunteers and from 1,510 rooms for the residual fauna, 22,901 female
      Culicidae were caught of which 167 anopheles, corresponding to 0.7%, the
      remaining 98.5% being Culex quinquefasciatus. This was the species that thus
      explained the mosquito-nuisance of which the inhabitants of the southern District
      complained during the period of survey. The female anopheles collected belonged
      to 2 species, An. arabiensis for 97.6% of those caught and An. pharoensis for
      2.4%. An. arabiensis were very slightly represented in the southern District with
      a density of aggressive females of 0.26 bite/man/night (B/M/N) and a density per
      room of 0.05 female. The aggressive populations appeared to be relatively
      important only at the end of the rainy season (September-October) with an average
      of 0.65 B/M/N in sites located at the periphery of the district with a maximum of
      1.33 B/M/N. The highest density of endophilic females registered at the end of
      the rainy season was 0.1 and its highest value in a given site was 0.36
      female/room. The parturity rate of aggressive females was 43.5% and those
      collected in houses of 84% with an anthropophilic index of 0.98. None of the
      dissected An. arabiensis females (77.3% of those collected) was a carrier of
      Plasmodium sporozoites and the circum-sporozoite antigen was not found. A very
      weak density of An. arabiensis and absence of plasmodial infection among
      dissected females favoured the absence of malarial transmission in the southern
      District for the period considered. However malaria transmission could not be
      absolutely ruled out given the presence of hematozoa carriers, as was revealed by
      the longitudinal follow-up of a cohort carried out concurrently with the
      entomological prospections of whom some were residents having declared permanent
      residence in the city for over two years. This entomological data explain the
      results of the afore mentioned parasitological survey which, with a registered
      plasmodic index of 0.3%, means that the southern District can be considered as
      non endemic. The area is however exposed to the risk of epidemic malaria
      following an important proliferation of anopheles, which is always possible after
      heavy rains and flooding and/or an important immigration of persons coming from
      regions of high malarial endemicity.

PMID- 9773208
TI  - Immunomodulators for Crohn's disease.

PMID- 9773209
TI  - Acid suppression therapy.

PMID- 9773210
TI  - Solid-phase ELISA for tissue transglutaminase, an endomysial target for possible
      serological diagnosis of celiac disease.

PMID- 9773211
TI  - Correcting reflux laparoscopically.
AB  - Most operations in the abdominal cavity and chest can be performed using
      minimally invasive techniques. As yet it has not been determined which
      laparoscopic procedures are preferable to the same operations done through
      conventional laparotomy. However, most surgeons who have completed the learning
      curves of these procedures believe that most minimally invasive techniques will
      be scientifically recognized soon. The evolution, validation and justification of
      advanced laparoscopic surgical methods seem inevitable. Most believe that the
      trend towards procedures that minimize or eliminate the trauma of surgery while
      adhering to accepted surgical principles is irreversible. The functional results
      of laparoscopic antireflux surgery in the seven years since its inception have
      been virtually identical to the success curves generated with open fundoplication
      in past years. Furthermore, overall patient outcomes with laparoscopic procedures
      have been superior to outcomes with the traditional approach. Success is
      determined by patient selection and operative technique. Patient evaluation
      should include esophagogastroduodenoscopy, barium swallow, 24 h pH study and
      esophageal motility study. Gastric emptying also should be evaluated. Patients
      who have abnormal propulsion in the esophagus should not receive a complete
      fundoplication (Nissen) because it adds a factor of obstruction. Dor or Toupet
      procedures are adequate alternatives. Prokinetic agents, dilation or pyloroplasty
      are used for pyloric obstruction ranging from little to more severe. Correcting
      reflux laparoscopically is more difficult in patients with obesity, peptic
      strictures, paraesophageal hernias, short esophagus, or a history of previous
      upper abdominal or antireflux surgery.

PMID- 9773212
TI  - Hypertensive pancreatic sphincter.
AB  - Major papilla pancreatic sphincter dysfunction, a variant of sphincter of Oddi
      dysfunction, causes pancreatitis or pancreatic-type pain. Endoscopic manometry as
      performed at endoscopic retrograde cholangiography is the most commonly used
      method to identify sphincter dysfunction. Noninvasive testing, such as secretin
      stimulated ultrasound analysis of duct diameter, is less reliable and of
      relatively low sensitivity. Two-thirds of patients with sphincter of Oddi
      dysfunction have elevated pancreatic basal sphincter pressure. Patients with
      suspected or documented sphincter of Oddi dysfunction may respond to biliary
      sphincterotomy alone, but warrant evaluation of their pancreatic sphincter if
      symptoms persist after therapy. Whether such pancreatic and biliary sphincters
      should be treated at the first treatment session is controversial. Pancreatic
      sphincterotomy is associated with a complication rate very similar to that of
      biliary sphincterotomy except that the pancreatitis rate is two- to fourfold
      higher. Prophylactic pancreatic stenting diminishes such pancreatitis by
      approximately 50%.

PMID- 9773214
TI  - Asymptomatic esophageal varices should be endoscopically treated.
AB  - Endoscopic treatment has generally been accepted in the management of bleeding
      esophageal varices. Both the control of acute variceal bleeding and elective
      variceal eradication to prevent recurrent bleeding can be achieved via endoscopic
      methods. In contrast to acute and elective treatment, the role of endoscopic
      therapy in asymptomatic patients who have never had variceal bleeding remains
      controversial because of the rather disappointing results obtained from
      prophylactic sclerotherapy. Most published randomized controlled trials showed
      that prophylactic sclerotherapy had no effect on survival. In some studies,
      neither survival rate nor bleeding risk was improved. In this article, the author
      champions the view that asymptomatic esophageal varices should be endoscopically
      treated.

PMID- 9773213
TI  - Cancer of the esophagus--endoscopic ultrasound: selection for cure.
AB  - Several treatment options are available to treat esophageal cancer. Ideally,
      treatment should be individualized, based on the projected treatment outcome for
      that individual. Accurate staging of the extent of the disease at the time of
      diagnosis offers the most rational attempt at stratifying patients into
      categories that can be used to affect treatment choices. Endoscopic
      ultrasonography (EUS) is the most accurate nonoperative technique for determining
      the depth of tumour infiltration and thus is accurate in predicting which
      patients will be able to undergo complete resection. EUS is also being used for
      tumour staging in order to guide treatment decisions in patients with esophageal
      cancer.

PMID- 9773215
TI  - Endoscopic mucosal resection for esophageal and gastric mucosal cancers.
AB  - Accumulated data from surgically resected specimens reveal that mucosal cancers
      of the esophagus and stomach pose low risk of lymph node metastasis. The author
      used endoscopic mucosal resection (EMR) as curative treatment in 142 cases of
      esophageal cancer and 102 cases of stomach cancer. In absolutely indicated cases
      there has been no local or distant metastasis during the longest period of follow
      up (nine years). One perforation and one post-treatment severe stenosis, which
      was resistant to dilation therapy in the esophagus, were encountered. Deeper
      layer resection (including partial proper muscle) occurred in the stomach in
      three cases where the lesions were positioned to the lesser curvature of the
      upper part of the stomach. Two cases of gastric mucosal resection leaving
      residual cancer were successfully treated by laser ablation. No case has required
      further surgery. Resected specimens were contributed to histological evaluation
      in all cases. In conclusion, EMR can be considered as the first-line treatment
      for selected cases of early stage esophageal and stomach cancer.

PMID- 9773216
TI  - Geriatric psychiatry in Canada.

PMID- 9773217
TI  - Geriatric psychiatry subspecialization in Canada: past, present, and future.
AB  - OBJECTIVE: To describe the development, future challenges, and directions of
      geriatric psychiatry in Canada. METHOD: This review and description of geriatric
      psychiatry was developed in the context of the criteria established by the Royal
      College of Physicians and Surgeons of Canada for subspecialization applications.
      Information from key informants, both nationally and internationally, was
      combined with a review of relevant literature in the field. RESULTS AND
      CONCLUSIONS: Canada has provided important contributions to the field of
      geriatric psychiatry in Canada and abroad. The increased needs of older persons
      with severe mental illness and their families, combined with a significant body
      of knowledge and therapeutic options, provide an important foundation for further
      development. Subspecialization in geriatric psychiatry as part of the overall
      development of psychiatry in Canada is proposed as critical to meeting the
      challenges of our aging population.

PMID- 9773218
TI  - The pharmacologic treatment of Alzheimer's disease: a guide for the general
      psychiatrist.
AB  - OBJECTIVE: To review the drug treatment of Alzheimer's disease (AD) and to
      provide guidelines for the physician on how to integrate these treatments into
      the overall management of this disorder. METHOD: A qualitative review of
      randomized, double-blind, placebo-controlled trials of medications used to treat
      cognitive deficits, disease progression, agitation, psychosis, or depression in
      AD. A computerized search of Medline was used to identify relevant literature
      published during the period 1968-1998. Key words used in the search were
      'randomized controlled trials,' with 'dementia' and with 'Alzheimer's disease'.
      RESULTS: Agents that are currently available in Canada to treat the cognitive
      deficits of AD include donepezil, ginkgo biloba, selegiline, and ergoloid
      mesylates. Donepezil and ginkgo biloba are associated with a statistically
      significant but clinically modest improvement in cognitive function in a
      substantial minority of patients with mild to moderate AD. Selegiline may have a
      mild beneficial effect on cognitive function in some patients with AD, but the
      data are inconclusive. Ergoloid mesylates have questionable efficacy in AD and
      can only be recommended as a last line of treatment. The results of a single
      trial suggest that vitamin E or selegiline (both have antioxidant properties) may
      slow the progression of AD. Antipsychotic medications can result in clinically
      significant improvement in agitation and psychosis. Carbamazepine also appears to
      be an effective treatment for agitation in AD, and there is preliminary evidence
      that the selective serotonin reuptake inhibitor citalopram reduces irritability
      in this disorder. There is no evidence that other nonneuroleptic medications are
      more efficacious than placebo in treating agitation in AD. Limited data indicate
      that depression in dementia responds to antidepressant medication. CONCLUSION:
      These data indicate that selected medications can be used to treat cognitive
      deficits, disease progression, agitation, psychosis, and depression in AD.
      However, there is considerable heterogeneity in patients' responses to these
      medications. Pharmacotherapy needs to be considered as a component of a package
      of care that also includes psychosocial and environmental interventions and
      support of the caregiver.

PMID- 9773219
TI  - An integrated medical and psychosocial treatment program for psychotic disorders:
      patient characteristics and outcome.
AB  - OBJECTIVES: To provide an overview of a comprehensive and integrated case
      management program that incorporates principles of assertive community treatment
      and combines effective medical and psychosocial interventions and to present the
      results of a process and outcome evaluation of the program, with particular
      emphasis on its impact on service utilization and consumer satisfaction. METHOD:
      Data on demographic, clinical, and several outcome measures were collected on all
      patients who received care in the program for a minimum of 6 months. For process
      evaluation we assessed the extent to which the program adhered to its goals and
      satisfied the patients, their families, and community-service agencies. Outcome
      evaluation data on the number and length of hospital admissions were compared for
      each subject with individual historical data for a period equal to the time spent
      in the program. In addition, relapses of psychotic symptoms that did not result
      in hospital admissions were calculated for each patient while in the program.
      RESULTS: Demographic, clinical, and treatment characteristics of clients show
      that the program has succeeded in maintaining its focus on providing services to
      relatively chronically ill patients with psychotic disorders over a mean period
      of 3 years. The process-evaluation data indicated a high level of satisfaction by
      patients, families, and other service agencies with the services received.
      Information on outcome variable showed that the program achieved significantly
      lower rates of hospital admissions and relapse of psychosis than expected. There
      was a highly significant reduction achieved in the utilization of inpatient
      hospital resources for patients receiving care in the program. Most of the
      inpatient service utilization was attributed to patients either who were
      resistant to treatment with antipsychotic agents or who refused to accept or
      comply with medication. CONCLUSIONS: It is possible to provide effective
      continuity of care from inpatient treatment to community adjustment for most
      individuals with psychotic disorders across the spectrum by blending hospital and
      community resources within an integrated case-management model of care.

PMID- 9773220
TI  - The 15-year outcome of Chinese patients with schizophrenia in Hong Kong.
AB  - OBJECTIVE: To explore the differential outcome of schizophrenia in developed and
      developing countries. The 15-year outcome of patients with schizophrenia in Hong
      Kong is reported. METHOD: In a 15-year retrospective outcome study, 100 patients
      with first-onset schizophrenia in 1977-1978 were randomly selected for outcome
      assessment from a pool of 797 patient files. The patterns of outcome were
      assessed by the same set of instruments and methodology as in other centres,
      since Hong Kong is 1 of the World Health Organization (WHO) centres for the
      International Study of Schizophrenia (ISoS). RESULTS: Nineteen subjects were
      untraceable, and 10 subjects committed suicide. More than one-half of the
      subjects had a good symptomatic outcome, while about 20% of the subjects were
      rated as having a good psychosocial adjustment. Over the entire 15-year period,
      96% of the subjects were maintained on medications, and 79% were living with
      family members. CONCLUSION: Despite Hong Kong's developed economy, its
      schizophrenia outcome is similar to that in developing countries. The existence
      of good family support and active follow-up treatment may be important
      contributory factors to better outcome.

PMID- 9773221
TI  - [Child psychiatric day treatment centers in Quebec for children 0-12 years of
      age].
AB  - OBJECTIVES: The review lists the child psychiatry day-care centres in Quebec,
      evaluates their capacity, and describes them according to the age range for
      admission, the psychopathologies treated, and the parent involvement required.
      METHOD: The 26 programs selected, which are all associated with a hospital
      centre, assess and treat children aged 0 to 12 years on a day-care basis.
      Organization, clinical operation, and research are addressed during a
      semisupervised interview. RESULTS: The average capacity is 18 children (4 to 40),
      with a total capacity of 454 children. The number of preschool patients can be
      compared with the number of school patients. Few programs are dedicated to
      invasive development disorders, and one-third treat behavioural or emotional
      disorders. The larger capacity programs treat patients of both genders. Most
      programs are eclectic and encourage but do not require parental involvement.
      CONCLUSIONS: Results take into account different theoretical influences, the
      controversy about integration criteria and parent involvement, and the
      specificity of the child psychiatry mission.

PMID- 9773222
TI  - Pharmacologic treatments effective in both generalized anxiety disorder and major
      depressive disorder: clinical and theoretical implications.
AB  - OBJECTIVE: To review the efficacy of anxiolytics (alprazolam and azapirones) in
      major depressive disorder (MDD) and that of antidepressants in generalized
      anxiety disorder (GAD), thereby exploring the possible theoretical and clinical
      implications of this efficacy. METHOD: A Medline literature search was performed
      for the period January 1980 to September 1997 of randomized, double-blind
      comparison studies between anxiolytics and antidepressants in the acute treatment
      of adult patients with either MDD or GAD. RESULTS: Alprazolam, at doses double
      those generally recommended for anxiety disorders, appears to be as effective as
      tricyclic antidepressants (TCAs) in the acute treatment of mild to moderate MDD.
      Alprazolam was also found to have a more rapid onset of action than to TCAs,
      particularly for the improvement of anxiety, somatization, and insomnia. Two
      azapirones (buspirone and gepirone) also have demonstrated a modest acute
      antidepressant effect in preliminary studies, albeit only in a depressed
      outpatient sample with considerable anxiety at baseline. Finally, various
      antidepressant drugs (imipramine, trazodone, paroxetine) were shown to have, at
      the least, comparable efficacy to benzodiazepines (BZDs) in the acute treatment
      of GAD. CONCLUSIONS: The nonspecificity of treatment response suggests that GAD
      and MDD are 1) different expressions of a similar disorder with a common
      neurobiological substrate, 2) discrete diagnostic entities that respond to
      independent pharmacological effects of the same drugs, or 3) a combination of the
      two (heterogeneity hypothesis). The most relevant clinical finding is the
      efficacy of antidepressants in the acute treatment of GAD.

PMID- 9773223
TI  - Psychotherapy and disclosure: recent court decisions.
AB  - OBJECTIVE: To encourage mental health professionals concerned about the practice
      of psychotherapy to add their voices to the legal debate on disclosure. METHOD:
      Analysis of recent court decisions, in particular 2 Supreme Court of Canada
      judgements, R. v. O'Connor and R. v. Carosella, and 1 United States Supreme Court
      judgement, Jaffee v. Redmond. RESULTS: The lack of a common definition of
      psychotherapy may, in part, have made it awkward for mental health professionals
      to mount a concerted defence of psychotherapy dossiers. CONCLUSIONS: Unless
      mental health professionals develop a more robust justification and delimitation
      for privilege, in Canadian courts possible relevance of clinical material is
      likely to override concern for the patient's privacy interest. Future research
      might evaluate the impact of loss of privilege upon different types of
      psychotherapy.

PMID- 9773224
TI  - Thinking small: research designs appropriate for clinical practice.
AB  - Even though some treatments have been shown to be efficacious in clinical trials,
      there is no guarantee that they are effective with a specific patient. This
      article outlines some of the methods clinicians can use to evaluate the
      effectiveness of therapy with individual patients. These methods include 1) the
      before-after design, 2) the reversal design, 3) interrupted time series, and 4)
      multiple baselines. This paper recommends that patients who are being treated,
      whether privately or in hospital, be seen as experiments with a sample size of 1
      and that their progress be monitored using 1 of these methods.

PMID- 9773225
TI  - Hypomania and St John's wort.

PMID- 9773226
TI  - Apathetic form of thyrotoxicosis.

PMID- 9773227
TI  - Smoking cessation and clozapine side effects.

PMID- 9773228
TI  - Successful paroxetine treatment of major depression in an adult form of
      metachromatic leukodystrophy with cognitive disturbances.

PMID- 9773229
TI  - Surgery and psychiatric practice.

PMID- 9773230
TI  - A young man with first-episode psychosis: case presentation and discussion.
AB  - OBJECTIVE: To review and discuss the issues and challenges involved in the
      treatment of first-episode psychosis in young patients, including choice of
      appropriate antipsychotic agents and adjunctive medications, dosing regimens, and
      biopsychosocial interventions. METHODS: The case of a young man in his late teens
      with a history of substance abuse who experienced an acute dystonic reaction to
      treatment for his psychotic episode is presented and discussed. RESULTS: Each
      contributing author provides an evaluation of the intervention strategies
      presented in the patient's history and factors that influenced the treatment
      outcomes. CONCLUSIONS: The successful management of young patients with psychosis
      must go beyond the control of positive symptoms. A comprehensive psychosocial and
      psychoeducational approach combined with a well-tolerated treatment regimen can
      help the patient achieve positive outcomes.

PMID- 9773231
TI  - Issues of choice in second-generation antipsychotic agents.
AB  - OBJECTIVE: To identify and describe the most significant issues in optimal
      clinical use of the second-generation antipsychotics. METHODS: A case report of
      an elderly female with treatment-refractory psychosis, negative symptoms, and
      tardive dyskinesia is used to focus the discussion of the clinical decisions. The
      rationale for switching, the choice of an appropriate compound, and the practical
      issues of transition from her present treatment are addressed. CONCLUSIONS: The
      case illustrates a common clinical scenario, focusing on the practical clinical
      issues in changing treatments. It draws attention to the need to carefully
      monitor the switch from traditional to second-generation antipsychotics. This is
      particularly important in patients with severe symptoms, so as not to confuse
      withdrawal effects from present medications with apparent failure of the new
      treatments.

PMID- 9773232
TI  - Clinical case discussion: the elderly patient with psychosis.
AB  - OBJECTIVE: To present a clinical case of an elderly person with psychosis and to
      discuss associated diagnostic and treatment issues. METHODS: A case from 1 of the
      authors' clinical practices was presented in English and French to several groups
      of Canadian psychiatrists attending a teaching day on psychosis. Three geriatric
      psychiatrists acted as facilitators, soliciting the clinical experiences of the
      participants in the discussion. The authors integrated clinical content from
      these sessions with results of a Medline search on psychosis in elderly persons.
      RESULTS: The assessment of elderly patients with psychosis is more often than in
      younger patients by overlying organicity, including delirium due to illness or
      medication use, dementia, or sensory deficits. Treatment might further worsen
      cognitive, affective, and functional impairment through adverse effects such as
      extrapyramidal symptoms (leading to decreased mobility and general functioning),
      anticholinergic effects (predisposing to delirium), and hypotension (predisposing
      to falls). Newer antipsychotics with less hazardous side effect profiles have an
      increasing role, but they must be coupled with psychosocial support to maximize
      the patient's independent functioning and quality of life after discharge.
      CONCLUSIONS: Assessment and treatment of the elderly person with psychosis must
      consider a wide variety of biopsychosocial variables, seeking to minimize further
      treatment-related deterioration. Controlled studies of antipsychotics in elderly
      people must be conducted in a variety of diagnostic situations that reflect their
      actual use in the community, and information must be propagated effectively among
      general psychiatrists, family physicians, and geriatric psychiatrists. The role
      of nonpharmacologic interventions in elderly persons with psychosis is even less
      well understood and deservers further study.

PMID- 9773233
TI  - Assessment and management of antipsychotic-induced adverse events.
AB  - OBJECTIVE: To review and discuss the spectrum of adverse events caused by
      antipsychotic agents that can directly influence the outcome of treatment by
      interfering with patient acceptance of and adherence to therapy. METHOD: The
      adverse effects of traditional and second-generation antipsychotic medications
      were discussed during a series of clinical workshops attended by psychiatrists
      from across Canada. The various adverse effects of antipsychotic drugs as well as
      their assessment and management are reviewed. RESULTS: Simple techniques for
      assessing adverse effects such as extrapyrimidal symptoms (EPS) are described. In
      some cases, adverse effects can be managed by dosage reduction and/or the use of
      adjunctive therapies such as antiparkinsonian agents and benzodiazepines.
      However, in some patients dose reduction carries the risk of symptom reemergence,
      while the commonly used adjunctive medications are associated with adverse
      effects of their own. CONCLUSIONS: Treatment-related side effects often require a
      reduction in dosage or a change in medication. Proper management can help
      encourage patient compliance and improve the outcome of antipsychotic treatment.
      The availability of the newer atypical antipsychotics offers another alternative,
      because they are associated with a much lower incidence of antipsychotic-induced
      side effects.

PMID- 9773234
TI  - Dyskeratosis congenita: multisystemic disorder with special consideration of
      immunologic aspects. A review of the literature.
AB  - Dyskeratosis congenita (DC) is a rare, predominantly X-linked multisystemic
      disorder. It demonstrates a wide spectrum of clinical manifestations and
      typically presents with dermatologic symptoms during the first decade of life.
      This review of the literature points out the importance of hematologic and
      immunologic alterations in defining the course and prognosis of the disease
      process. Pancytopenia as well as the humoral and cellular disturbances in
      immunologic functions associated with this disease complex may lead to severe
      infections that represent the main cause of death. The pathogenesis of DC is
      still unclear and a curative therapy is presently lacking. Recent reports suggest
      that a beneficial effect may be observed in the administration of hematopoietic
      growth factors (G-CSF, GM-CSF) for patients with DC and neutropenia.

PMID- 9773235
TI  - Pneumococcal bacteremia and focal infection in young children.
AB  - We reviewed a consecutive case series of 178 immunocompetent children aged 3-36
      months without central venous lines who had blood cultures positive for
      Streptococcus pneumoniae by either of paired broth and quantitative culture
      methods. The incidence of accompanying focal infection was significantly greater
      in patients with > 10 colony-forming units (cfu)/mL than in patients with < or =
      10 cfu/mL (30.4% vs 12.9% respectively, p = 0.04). No significant relationships
      existed between the magnitude of bacteremia and the age, gender, presenting
      temperature, interval until the blood culture turned positive, total peripheral
      blood white cell count, absolute neutrophil count, or absolute band count.
      Overall, the quantitative method detected 59/178 (33.1%) of the isolates,
      including five isolates (2.8%) that the broth method failed to detect.

PMID- 9773236
TI  - Infants with birth weight 1,000-1,499 grams born in three time periods: has
      outcome changed over time?
AB  - The objective of this study was to see whether outcome of infants of larger birth
      weight (1,000-1,499 grams) has changed with advances in neonatology. The outcome
      of infants born in a recent time period (1989-1991) was compared with that of
      infants born previously, in 1984-1986 and 1979-1981. Univariate analyses were
      conducted on the association of medical risk factors and date of birth with
      outcome. More than 90% of infants in each time period were neurologically normal
      and more than 80% were cognitively normal. Predictor variables were intracranial
      hemorrhage for poor neurologic outcome and days on oxygen for poor cognitive
      outcome. We found that neurodevelopmental outcome was stable over three time
      periods.

PMID- 9773237
TI  - Follow-up of the low-birth-weight infant: where do we go from here?

PMID- 9773239
TI  - Use of bilevel positive airway pressure (BIPAP) in end-stage patients with cystic
      fibrosis awaiting lung transplantation.
AB  - Nine consecutive end-stage patients with cystic fibrosis (CF) awaiting lung
      transplantation were admitted to the pediatric intensive care unit (PICU) in
      respiratory decompensation. They all received noninvasive bilevel positive airway
      pressure (BIPAP) support and were evaluated to determine whether or not it
      improved their oxygenation and provided them with long-term respiratory
      stability. BIPAP was applied to all patients after a brief period of assessment
      of their respiratory status. Inspiratory and expiratory positive airway pressures
      (IPAP, EPAP) were initially set at 8 and 4 cm H2O respectively. IPAP was
      increased by increments of 2 cm H2O and EPAP was increased by 1 cm H2O increments
      until respiratory comfort was achieved and substantiated by noninvasive
      monitoring. Patients were observed in the PICU for 48 to 72 hours and then
      discharged to home with instructions to apply BIPAP during night sleep and
      whenever subjectively required. Regular follow-up visits were scheduled through
      the hospital-based CF clinic. The patients' final IPAP and EPAP settings ranged
      from 14 to 18 cm H2O and 4 to 8 cm H2O, respectively. All nine patients showed a
      marked improvement in their respiratory status with nocturnal use of BIPAP at the
      time of discharge from the PICU. Their oxygen requirement dropped from a mean of
      4.6 +/- 1.1 L/min to 2.3 +/- 1.5 L/min (P < 0.05). Their mean respiratory rate
      decreased from 34 +/- 4 to 28 +/- 5 breaths per minute (P < 0.05). The oxygen
      saturation of hemoglobin measured by pulse oximetry, significantly increased from
      a mean of 80% +/- 15% to 91% +/- 5% (P < 0.05). The patients have been followed
      up for a period of 2 to 43 months and have all tolerated the use of home
      nocturnal BIPAP without any reported discomfort. Six patients underwent
      successful lung transplantation after having utilized nocturnal BIPAP for 2, 6,
      14, 15, 26, and 43 months, respectively. Three patients have utilized home BIPAP
      support for 2, 3, and 19 months, respectively, and continue to await lung
      transplantation. An acute development of refractory respiratory failure resulted
      in the demise of the remaining three patients after having utilized BIPAP for 3,
      6, and 10 months, respectively. The authors conclude that BIPAP therapy improves
      the respiratory status of decompensating end-stage CF patients. It is well
      tolerated for long-term home use and provides an extended period of respiratory
      comfort and stability for CF patients awaiting lung transplantation.

PMID- 9773238
TI  - Basilar artery occlusion and the dense artery sign in the newborn.
AB  - A child with basilar artery occlusion in the neonatal period is reported. The
      occlusion was documented by unenhanced computed tomography performed in the
      neonatal period demonstrating a "dense" artery at the tip of the basilar artery.
      The pattern of cerebral damage on MRI scan at 10 years of age confirmed the site
      of the vascular occlusion. The evidence suggests that embolization was the
      operating pathogenic mechanism of cerebral vascular occlusion. Neonatal arterial
      thrombosis involving the carotid circulation has been well documented and may be
      due to many pathological factors including direct trauma to the carotid artery
      and embolization from remote sites. Thrombosis of the vertebral artery in the
      neonate is only rarely reported and only in association with significant cervical
      trauma. A second child with a similar pattern of cerebral injury demonstrated on
      neuroimaging is described suggesting that this event may be more common than
      recognized. The clinical features of basilar artery occlusion as seen in the
      adult are not apparent in the neonate. Recognition of the neuroimaging
      characteristics seen in this condition may help to provide the clinician with a
      reasonable pathogenetic explanation for unexplained cerebral injury.

PMID- 9773240
TI  - Abdominal pain in a girl with juvenile dermatomyositis.

PMID- 9773241
TI  - Myopathic changes as a paraneoplastic sign in childhood acute lymphoblastic
      leukemia.

PMID- 9773242
TI  - Acute rheumatic pancarditis associated with poststreptococcal acute
      glomerulonephritis: a patient report.

PMID- 9773243
TI  - Nutrition and pulmonary function predictors of delayed puberty in adolescent
      males with cystic fibrosis.

PMID- 9773244
TI  - Risk of HIV transmission.

PMID- 9773245
TI  - Treatment of acute gastroenteritis in infants.

PMID- 9773246
TI  - Autoantibodies as a clinical diagnostic tool. Introduction.

PMID- 9773247
TI  - Autoantibodies in angioneurotic edema.

PMID- 9773249
TI  - The measurement of antithyroid autoantibodies in the diagnosis and management of
      thyroid autoimmune disease.

PMID- 9773248
TI  - Anti-DNA antibodies as early predictor for disease exacerbations in SLE.
      Guideline for treatment?

PMID- 9773250
TI  - The clinical significance of antityrosinase antibodies in melanoma and related
      hypopigmentary lesions.
AB  - Antityrosinase antibody is a newly detected antibody in the sera of patients with
      melanoma or vitiligo. The serum level of the antibody is measured by enzyme
      linked immunosorbent assay (ELISA). The autoantigen is tyrosinase itself, the
      enzyme that participates in pigment (melanin) formation by both melanocytes and
      melanoma cells Antityrosinase IgG antibodies were found to be present in high
      titers in sera of patients with vitiligo in comparison to patients with melanoma
      or healthy volunteers. The level of antityrosinase antibodies in patients with
      metastatic melanoma was significantly higher than the level in healthy subjects,
      but insignificantly higher than the level in patients with no evidence of
      disease. Patients with melanoma and MAH (melanoma-associated hypopigmentation;
      vitiligo-like) had the same level of antityrosinase antibodies as the controls or
      the patients with metastatic melanoma. This observation reflected the possible
      absorption of antityrosinase antibodies by melanoma antigens, and pointed to the
      participation of the antibodies in the destruction of normal melanocytes in
      patients with melanoma, as part of the immune reaction towards this disease. The
      most interesting observation was the high level of antityrosinase antibodies in
      patients with vitiligo in comparison with the low level in patients with
      melanoma, patients with MAH, and patients with NED. Although the cutaneous
      manifestations of vitiligo and MAH are similar and result from destruction of
      melanocytes by specific antibodies, the two situations are immunologically
      different. The serum level of free antityrosinase antibodies could not serve as
      marker for the state of the disease or disease progression or relapse, as no
      significant difference could be detected between the levels in patients without
      evidence of disease to those with metastatic melanoma; nor could the levels of
      antityrosinase antibodies differentiate between the different sites of the
      primary lesion. However, we have shown that antityrosinase antibodies could be
      used for monitoring the response to active specific immunotherapy by injection of
      anti-idiotypic antibodies mimicking the HMW-MAA. In the future, antityrosinase
      antibodies may be incorporated into immunotherapy for malignant melanoma.

PMID- 9773251
TI  - Heparin-induced thrombocytopenia and thrombosis.

PMID- 9773252
TI  - Cryoglobulins and cryoglobulinemia. Diagnostic and therapeutic considerations.

PMID- 9773253
TI  - Clinical utility of autoantibodies in Guillain-Barre syndrome and its variants.

PMID- 9773255
TI  - Autoimmune hemolytic anemia.
AB  - Six types of autoimmune hemolytic anemias have been described. Table 1 provides
      summary highlights for each type of AIHA. WAIHA accounts for the majority of
      cases, followed by CAIHA and DIAHA. In recent years, AIHA status post-BMT has
      been noted to occur more often than previously reported, particularly in T-cell
      depleted graft recipients. The clinical presentation is diverse among the various
      types of AIHAs: WAIHA cases may require a complex treatment regimen if unstable
      hemolytic anemia is present, and often permanent remission is infrequent. In
      contrast, CAIHA in younger patients (status postinfection) is frequently
      asymptomatic and self-limiting. If AIHA is suspected in a patient with clinically
      significant presentation, it is important to communicate with the transfusion
      service since specific tests to confirm these diagnoses are not routinely done.
      Special procedures may be necessary to identify underlying rbc alloantibodies
      prior to transfusion. In a patient pre-operative for cardiopulmonary-bypass
      surgery, CAIHA antibody testing should be done. When found, pre-operative
      management may lessen the risk of serious consequences such as hemolysis, renal
      failure, and myocardial damage. AIHA associated in BMT recipients is frequently
      severe, and, in some cases may be refractory to treatment despite complex
      management strategies. Further studies are needed to acquire a better
      understanding of the pathogenesis of BMT-associated AIHA.

PMID- 9773254
TI  - Central nervous system (CNS) involvement in SLE. The diagnostic role of
      antibodies to neuronal antigens.

PMID- 9773256
TI  - Functional properties of antiendothelial cell antibodies.

PMID- 9773258
TI  - Autoantibodies to coagulation factors and bleeding disorders.

PMID- 9773257
TI  - ANCA testing. New developments and clinical implications.

PMID- 9773260
TI  - Two-year treatment with oral contraceptives in hyperprolactinemic patients.
AB  - The aim of this prospective study was the follow-up for 2 years in symptoms,
      serum prolactin (PRL) levels, and radiological aspects of a group of young
      patients using oral contraceptives (OC) with hyperprolactinemia. A total of 16
      hyperprolactinemic women (eight with idiopathic hyperprolactinemia and eight with
      pituitary microadenoma) who started OC use were admitted in the study. After 2
      years of OC use, the assessable patients showed a nonsignificant decrease in
      plasma PRL level (26.8 +/- 29.4 micrograms/mL, range 4.2-97.1 micrograms/mL vs
      56.3 +/- 31.5 micrograms/mL, range 23.5-144 micrograms/mL). No patient
      experienced any radiological changes during OC treatment. In conclusion, although
      the number of observations is limited, the data suggest that after 2 years of
      follow-up, no harmful effect of OC use was observed in these patients.

PMID- 9773259
TI  - Anti-DNA, antihistone, and antinucleosome antibodies in systemic lupus
      erythematosus and drug-induced lupus.

PMID- 9773261
TI  - A randomized cross-over study on various hormonal parameters of two triphasic
      oral contraceptives.
AB  - The effect of two triphasic oral contraceptives (Triquilar [TRQ] and Trisiston
      [TRS]) containing ethinyl estradiol (EE) and levonorgestrel (LNG) on various
      hormonal parameters was investigated in 26 women during a cross-over study. TRS
      consisted of 0.03 mg EE + 0.05 mg LNG (six tablets), 0.04 mg EE + 0.075 mg LNG
      (six tablets), and 0.03 mg EE + 0.15 mg LNG (nine tablets), whereas TRQ was
      different in the second phase (five tablets) and third phase (10 tablets). Blood
      samples were taken on days 6, 11, 21, and 28 of the control and washout cycles
      and the third treatment cycle. Both formulations inhibited ovulation reliably and
      decreased the serum levels of gonadotropins, free testosterone, and
      dehydroepiandosterone sulfate in a time-dependent manner, whereas estradiol and
      testosterone were already suppressed on day 6, indicating a direct suppressive
      effect on ovarian steroid synthesis. Prolactin, which rose sporadically in some
      women, was not significantly changed. In contrast, the levels of sex hormone
      binding globulin, corticosteroid binding globulin, and cortisol were
      significantly elevated by 100%. During the hormone-free interval of 7 days, all
      parameters returned at least partly to baseline. There was no significant
      difference between the effects of both formulations. The results suggest the
      possibility of a direct inhibitory effect of contraceptive steroids on ovarian
      steroid synthesis.

PMID- 9773262
TI  - Effect of two oral contraceptives containing ethinyl estradiol and gestodene or
      norgestimate on different lipid and lipoprotein parameters.
AB  - The effect of a triphasic oral contraceptive containing ethinyl estradiol and
      gestodene (EE/GSD) on various lipid and lipoprotein parameters was compared with
      that of a monophasic formulation containing 35 micrograms ethinyl estradiol and
      250 micrograms norgestimate (EE/NGM). Blood samples were collected from 46 women
      on days 2, 11, and 21 of the preceding control cycle and of the third, sixth, and
      twelfth treatment cycles. There was no significant difference between
      formulations with regard to the influence on any measured parameter. As compared
      with controls, a significant increase was observed in the plasma levels of total
      triglycerides (24-78%), total phospholipids (7-20%), very low density lipoprotein
      (VLDL) triglycerides (61-76%), VLDL-phospholipids (14-60%), low density
      lipoprotein (LDL) triglycerides (8-35%), LDL-phospholipids (28-30%), high density
      lipoprotein (HDL) cholesterol (8-16%), HDL 3-cholesterol (11-20%), HDL
      triglycerides (17-66%), HDL-phospholipids, HDL 3-phospholipids (7-11%),
      apolipoprotein (apo) A-I (5-20%) and apo A-II (10-40%) during treatment with both
      formulations. In contrast, the LDL-cholesterol levels were significantly
      decreased. These changes in lipid metabolism appear to reflect a predominance of
      the effect of the estrogen component. The results indicate that both low dose
      oral contraceptives containing different progestins and different amounts of EE
      do not exert a deleterious effect on lipoprotein metabolism, as high HDL
      cholesterol and low LDL-cholesterol levels are known as low risk factors of
      cardiovascular disease. In contrast to endogenous hypertriglyceridemia, an EE
      induced rise in triglyceride levels does not appear to increase cardiovascular
      risk if LDL is not increased.

PMID- 9773263
TI  - Effects on the hemostatic system and liver function in relation to Implanon and
      Norplant. A prospective randomized clinical trial.
AB  - In this prospective randomized clinical trial, two long-term contraceptive
      implants were studied with respect to hemostasis and liver function in 86 healthy
      young women. The two implants used were Implanon, containing the progestagen
      etonogestrel (the biologically active metabolite of desogestrel) and Norplant,
      the implant containing the progestagen levonorgestrel. The results of the trial
      showed that both implants had similar small effects on the hemostatic system that
      are not suggestive of a tendency towards thrombosis. The effect on liver function
      was characterized by increases in total bilirubin and gamma-glutamyl transferase
      and decreases in alanine aminotransferase and aspartate aminotransferase.

PMID- 9773264
TI  - A pilot study of the effect of methotrexate or combined oral contraceptive on
      bleeding patterns after induction of abortion with mifepristone and a
      prostaglandin pessary.
AB  - Although a combination of mifepristone and a prostaglandin is a safe, acceptable
      alternative to vacuum aspiration for inducing abortion in early pregnancy, the
      longer period of vaginal bleeding after medical abortion is a disadvantage. The
      present study investigated whether administration of the combined oral
      contraceptive pill (COC) or the injection of methotrexate at the time of abortion
      would shorten the period of vaginal bleeding after medical abortion. After having
      a medical abortion induced with mifepristone (200 mg) and 0.5 mg gemeprost
      pessary, 80 women were randomized to four groups of 20 women each; Group A, COC;
      Group B, control; Group C, 50 mg/m2 methotrexate; and Group D, placebo injection.
      There was no significant difference in the duration of bleeding between Groups A
      and B (median 14 and 17 days) or between Groups C and D (18 and 15 days), or in
      the amount of bleeding (4 days of heavy bleeding in each group). The first period
      occurred sooner in Group A who took the COC (median/range: 25/15-54 control group
      versus 32/16-46 days, p < 0.04). The administration of methotrexate was
      associated with a temporary elevation in liver enzyme concentration in one woman.
      It is concluded that women who wish to use COC can start immediately after
      medical abortion. Addition of methotrexate after abortion has no significant
      beneficial effect on patterns of bleeding and cannot be recommended.

PMID- 9773265
TI  - The risk of inadvertent intrauterine device insertion in women carriers of
      endocervical Chlamydia trachomatis.
AB  - The most important complication attributed to the use of intrauterine device
      (IUD) is pelvic inflammatory disease (PID), often associated with Neisseria or
      Chlamydia infection. Consequently, the IUD should not be inserted in women at
      risk of infection or with symptoms of endocervicitis. To evaluate the
      effectiveness of such a policy, a systematic investigation of Chlamydia and
      Neisseria was carried out among 407 contraceptive acceptors. Twenty-seven cases
      were positive for Chlamydia and none were positive for Neisseria. There were no
      statistical differences in the proportion of women with and without Chlamydia who
      had vulvovaginal or cervical signs or symptoms, although twice as many women had
      pain at pelvic exam in the Chlamydia-infected group. In 29 women in whom
      infection was clinically suspected, two were found to be infected with Chlamydia.
      IUD were not inserted in women suspected of having infection, but 19 of 327 IUD
      acceptors were subsequently found to have a positive Chlamydia test result. Two
      women returned with symptoms of PID and 17 were asymptomatic, but all were
      treated. PID was not suspected in any other subject. These results reinforce the
      need for careful selection of IUD acceptors and for thorough counseling for
      symptoms of PID and the need for immediate consultation.

PMID- 9773267
TI  - Intravasal contraception with styrene maleic anhydride and its noninvasive
      reversal in langur monkeys (Presbytis entellus entellus).
AB  - In male langurs with azoospermia induced by vas occlusion with styrene maleic
      anhydride (SMA), the exploratory feasibility of azoospermia reversal by a new
      noninvasive reversal procedure has been assessed. Palpation, percutaneous
      electrical stimulation of the vas deferens, forced vibratory movement, suprapubic
      percussion, and per rectal digital massage of the vas deferens are the components
      of the multimodal noninvasive reversal procedure. The exploratory investigation
      reveals that a single application of the procedure leads to reversal of
      azoospermia. Normospermia with normal motility and viability appears after third
      ejaculation onwards after reversal manipulations. Ultrastructure of the
      spermatozoa, using scanning and transmission electron microscopy, revealed that
      the spermatozoa attained normalcy and sperm functional tests (i.e., hypo-osmotic
      swelling test, slide test for acrosome intactness, and test for sperm
      mitochondrial activity index) further confirmed the normalcy of the spermatozoa
      toward their fertilizing ability. Semen biochemistry appeared normal throughout
      the course of investigation. The morphology of the vas deferens, which showed
      exfoliation of the epithelium, was in the process of regaining normalcy after 90
      days of reversal manipulations. The results suggest that noninvasive reversal
      technique offers the possibility of the functional azoospermia reversal within a
      short period of time.

PMID- 9773266
TI  - Antinidatory effect of luteal phase administration of mifepristone (RU486) is
      associated with changes in endometrial prostaglandins during the implantation
      window.
AB  - Luteal phase administration of mifepristone provides a significant degree of
      pregnancy protection to monkeys and women. Among several proposed mediators of
      the antinidatory action of luteal phase mifepristone, prostaglandins (PG) at the
      endometrial level appear important, and was examined in the present study using
      the rhesus monkey as the primate model. To this end, the concentrations of PGE2
      and PGF2 alpha in endometrium and the profiles of cyclooxygenase (COX) and 15
      hydroxy prostaglandin dehydrogenase (PGDH) were examined in untreated control
      animals, in animals subjected to mifepristone treatment (2 mg/day) alone or along
      with diclofenac (25 mg/day), or along with a PGE1 analog (100 micrograms
      misoprostol), in animals subjected to diclofenac alone treatment, and in animals
      treated with misoprostol alone on cycle days 16, 17, and 18. Tissue samples were
      collected on day 20 of treatment cycles from animals with discernible corpora
      lutea. Early luteal phase treatment with diclofenac did not result in any
      remarkable change in endometrial prostaglandin concentrations, however, there was
      an increase in the profile of COX. Animals exposed to misoprostol in the
      prereceptive stage, on the other hand, exhibited decreased expression of
      endometrial COX. The concentrations of PGF2 alpha and PGE2, as well as the ratios
      of PGF2 alpha to PGE2 concentrations, were increased along with a decrease in COX
      and PGD in endometrial samples following luteal phase mifepristone treatment.
      Although the underlying cellular mechanism of regulation of COX and PGDH in
      mifepistone-treated endometrium remains to be examined, the decrease in PG
      catabolism through low PGDH may contribute to the increased PG and high ratio of
      PGF2 alpha to PGE2 in mifepristone-exposed endometrium. It is plausible that
      mifepristone action on endometrial cells is mediated by an altered ratio of PGF2
      alpha to PGE2. Furthermore, it appears that the regulation of PG milieu by COX
      and PGDH activities in reproductive tissues is under complex regulatory mechanism
      and is temporarily correlated with specific developmental events.

PMID- 9773268
TI  - Antiovulatory and postcoital antifertility activity of the antiprogestin CDB-2914
      when administered as single, multiple, or continuous doses to rats.
AB  - The present studies in rats were undertaken to investigate the potential of a new
      antiprogestin, CDB-2914, for use as an emergency postcoital contraceptive for
      women. When given orally at noon on the day of proestrus, both CDB-2914 and
      mifepristone displayed dose-dependent antiovulatory activity; however, CDB-2914
      was about eight times more potent than mifepristone. Both antiprogestins were
      considerably less potent in blocking ovulation when injected subcutaneously. To
      evaluate antifertility activity during continuous low dose administration, rats
      were dosed orally with 0.5 mg of either CDB-2914 or mifepristone daily,
      commencing on the day of estrus and continuing for 24 days. Females were
      cohabited with proven fertile males on day 8 of treatment and were removed 1-3
      days later after confirmed mating. The pregnancy rate was significantly reduced
      (p < 0.05) only in the CDB-2914-treated females; however, the mean number of
      normal implantation sites per pregnant rat was significantly reduced (p < 0.05)
      by mifepristone as compared with the vehicle control group. CDB-2914 was also
      found to prevent pregnancy when administered orally after mating from days 0-3
      during tubal egg transport, or from days 4-6 during the pre- and peri
      implantation periods. To determine the day of maximal sensitivity to CDB-2914, a
      single 2-mg dose per rat was given orally on days 0, 1, 2, 3, 4, or 5 postmating.
      This dose of CDB-2914 was without effect on pregnancy at days 0, 1, 2, or 3
      postmating. In contrast, 2 mg CDB-2914 per rat was highly effective in blocking
      pregnancy when given on either day 4 or 5 postmating. Collectively, these data
      demonstrate that CDB-2914 is an orally active postcoital antifertility agent that
      is more potent than mifepristone in the rat. Hence, CDB-2914 may prove to be an
      effective emergency postcoital contraceptive in women.

PMID- 9773269
TI  - Phenotypical response in different cell types of rat uterus to centchroman. A
      qualitative analysis.
AB  - To assess the alleged estrogenic and antiestrogenic profile of centchroman, a
      phenotypical response was studied in native uterine cells or migrant blood cells
      in adult ovariectomized rats under the influence of estradiol-dipropionate (EDP)
      and centchroman (CC) given per se and together. Histologic observations were
      divided arbitrarily into the following regions: luminal epithelium, superficial
      and deep stroma, and the two layers of muscularis. Glandular cell proliferation,
      mitoses, and vascularity were examined additionally. It was found that CC per se
      stimulated luminal epithelial cell height and glandular cell proliferation better
      than EDP. Leukocytic infiltration and vascularity were also more pronounced in
      the uteri of CC-treated rats. Furthermore, except for a slight reduction in
      glandular cell size and edematous condition of circular muscle layer, the changes
      remained unaffected after conjoint treatment of CC and EDP. The observations
      revealed that some of the nongenomic responses, elicited by the rat uterus after
      CC treatment, seem to be unrelated to the hormonal attributes of the molecule.

PMID- 9773270
TI  - Sequencing of a gene encoding a member of the mitochondrial carrier family of
      transport proteins from Aspergillus nidulans.
AB  - Mitochondrial carrier proteins comprise a superfamily of evolutionarily conserved
      proteins that regulate the specific transport of essential metabolites across the
      mitochondrial membranes. In this report we describe the cloning and sequencing of
      a gene from Aspergillus nidulans, amc-1, that encodes the first reported example
      of a mitochondrial carrier protein in Aspergillus species. The amc-1 gene is
      located on chromosome 7, and is transcribed as a 1.6 kb unspliced polyadenylated
      RNA. The predicted translation product of the amc-1. cDNA displays three tandemly
      repeated domains which possess protein signature motifs that are characteristic
      of mitochondrial carrier proteins that localize to the inner mitochondrial
      membrane. amc-1 shares the greatest similarity with a Neurospora mitochondrial
      carrier protein that is implicated in basic amino acid transport, suggesting that
      the amc-1 protein may provide a related function.

PMID- 9773271
TI  - Promoter structure and activity of type 1 rice metallothionein-like gene.
AB  - A novel stress-inducible metallothionein-like gene from rice, designated as rgMT
      1 (rice genomic metallothionein-like gene-1), was isolated and sequenced. From
      the sequence analysis of its 5'-flanking region, two putative TATA boxes, one
      CAAT box, and several short sequences homologous to regulatory cis-elements
      previously reported were identified. Two direct repeats, one 10 bp in length
      (CAAAATCAAA) and the other 11 bp (GTGAAAATACT), respectively, were also found. By
      transient GUS (beta-glucuronidase) assay, the expression of GUS, in vitro, was
      enhanced by the presence of the rgMT-1 intron. The critical region which controls
      the basal transcription was shown to lie between -73 and -36 upstream of rgMT-1,
      in which one of the two putative TATA boxes was located. The promoter activity
      was lost completely when both putative TATA boxes were deleted. This is the first
      report describing the genomic structure and regulation of a monocotyledonous
      metallothionein-like gene critical to the response of stress.

PMID- 9773272
TI  - Molecular characterization of a novel subtilisin inhibitor protein produced by
      Streptomyces venezuelae CBS762.70.
AB  - We report here on the isolation and identification of a gene coding for a novel
      subtilisin inhibitor (VSI) isolated from Streptomyces venezuelae CBS762.70. The
      vsi gene was isolated on a 5-kb chromosomal PvuII fragment as identified by DNA
      sequencing and inhibitor activity testing of the gene product. Primer extension
      studies revealed that the mRNA transcriptional start point was situated at -37
      and -36 relatively to the ATG start codon assuming the presence of solely one
      promoter. Vsi promoter strength was about double of those of ermE-P1a and aph-P1,
      as tested with the mRNA production of the aphII gene preceded by the respective
      promoters. Translation of the vsi coding sequence revealed a 28 amino acids long
      signal peptide. The mature VSI protein consists of 118 amino acids of which 87%
      was verified by N-terminal amino acid sequence analysis. Compared with the
      already known Streptomyces proteinase inhibitors, VSI shows a relatively high
      amino acid identity in the conserved domains. Nevertheless, only a maximum amino
      acid identity of 56.1% was noticed and some highly conserved residues were
      substituted in VSI. As a consequence, VSI could be classified within a separate
      group of Streptomyces subtilisin inhibitors.

PMID- 9773273
TI  - The 10Sa RNA gene of Thermus thermophilus.
AB  - The 10Sa RNA gene of Thermus thermophilus was isolated and sequenced. The tRNA
      like structure at the 5' and 3' ends and other secondary structure features of
      the T. thermophilus 10Sa RNA are similar to E. coli 10Sa RNA. A variant of the
      sequence motif coding for the tag peptide is located in the centre of T.
      thermophilus 10Sa RNA.

PMID- 9773274
TI  - DNA sequence analysis of the genes for the fowl adenovirus serotype 10 putative
      33K and pVIII.
AB  - The nucleotide sequence and genomic location of the fowl adenovirus serotype 10
      (FAV-10) putative 33K and precursor protein VIII (pVIII) genes have been
      determined. The total genomic region sequenced was 1814 base pairs (bp) in length
      with the 33K coding region occupying the sequence from nucleotides 44 to 634 and
      the pVIII coding region nucleotides 949 to 1689. The location of both the 33K and
      pVIII genes have the same positional organization as their human adenovirus (HAV)
      counterparts which is 3 prime (3') to the 100K gene. Along with the 100K the 33K
      and pVIII form the late transcription unit 4 (L4). The FAV-10 putative 33K coding
      region could encode a polypeptide of 196 amino acids in length with a relative
      molecular mass of 21.9 kilodaltons (kDa) while the pVIII produces a polypeptide
      of 246 amino acids with a calculated relative mass of 26.7 kDa. Two possible
      splice acceptor sites were identified one 5' to the 33K and one 5' to the pVIII
      coding regions. A putative poly A recognition sequence of AATAAA was identified
      3' to the pVIII, signaling the end of the L4 transcription unit.

PMID- 9773275
TI  - Ribosomal RNA genes of Phaseolus coccineus. IV. Structure and comparative
      analysis of the intergenic spacer: possible involvement of some nucleotides in
      the transcription control of coding sequences. Sequence of the intergenic spacer
      of ribosomal genes.
AB  - The sequence of the intergenic spacer (IGS) of Phaseolus coccineus is determined.
      The IGS contains three distinct regions: Region A, constant in length; Region B,
      heterogeneous in length among genes, including two very similar segments 162 and
      177 bp long, repeated two and nine times respectively in the investigated clone;
      Region C, constant in length, comprising five islands. The putative promoters and
      the sites of termination, processing and methylation are detected by a comparison
      with other plant systems.

PMID- 9773276
TI  - Identification of a putative BRF homologue in the genome of Caenorhabditis
      elegans.
AB  - We have identified a putative gene within the Caenorhabditis elegans genome which
      has the potential to encode a protein homologous to BRF, an RNA polymerase III
      general transcription factor. The predicted protein shares very similar overall
      structure with human and yeast BRF. In particular, its N-terminal half comprises
      a zinc-ribbon motif and a TR domain which is also present in the cyclin box. The
      C. elegans protein is more similar to human BRF than to the yeast BRF proteins,
      as would be expected from an evolutionary standpoint. Alignment of the C. elegans
      protein with the four known BRF proteins reveals two blocks conserved between all
      five sequences within the diverged C-terminal region. Profile searches using
      these regions suggest that they may contain evolutionarily conserved motifs.
      These comparisons provide insight into the structure and function of an important
      transcription factor.

PMID- 9773277
TI  - Molecular cloning and expression of feline interleukin-16.
AB  - Human IL-16 (hIL-16) is a homotetrameric cytokine with chemotactic properties
      towards cells expressing the CD4 receptor. This chemotactic cytokine plays an
      important role in attracting cells of the immune system to the site where CD8+ T
      cells were activated for example by a foreign antigen. In addition to the
      chemotactic activity, hIL-16 also induces expression of IL-2 receptor, increasing
      the responsiveness to IL-2 and therefore implying a role for specific expansion
      of the CD4+ T-cell population in an area of induced inflammation. In this report
      we describe the cloning, sequencing and the expression of feline IL-16 (fIL-16).
      At the nucleotide level, fIL-16 shows 84.6 and 84.5%, on the amino acid level 93
      and 91.5% identity to the human and African green monkey (agm) IL-16,
      respectively.

PMID- 9773278
TI  - Isolation and sequencing of a second Rhizobium tropici CFN299 genetic locus that
      contains genes homologous to amino acid sulphate activation genes.
AB  - A Rhizobium tropici CFN299 DNA region, homologous to genes involved in Nod factor
      synthesis and amino acid sulphate activation, was isolated from a genome library.
      DNA sequence analysis revealed two open reading frames, orf1 and orf2. orf1
      showed highest sequence similarity to the Escherichia coli cysD gene while orf2
      is closely related to Rhizobium sp. N33 nodQ. However, the orf2 deduced peptide
      is 152 amino acids shorter than Rhizobium sp. N33 NodQ, and lacks the 3'
      phosphoadenosine 5'-phosphosulphate-binding motif. A dendrogram based on the
      alignment of the deduced amino acid sequences of orf2/nodQ/cysN genes separated
      Escherichia coli cysN and orf2 from the nodQ cluster. Upstream of orf1, partial
      sequence analysis revealed the 3' part of an orf that is highly similar to E.
      coli cysH. The G + C content of orf1 and orf2 differs significantly from the G +
      C content of R. tropici symbiotic sulphate activation nodPQ genes. This data
      suggests that the isolated R. tropici CFN299 locus contains housekeeping genes
      for amino acid sulphate activation.

PMID- 9773279
TI  - Racial/ethnic labels are not necessary.

PMID- 9773280
TI  - Family physicians are praised by specialist.

PMID- 9773281
TI  - Smoky Hill is good example of how RRTs work.

PMID- 9773282
TI  - Focused teaching: facilitating early clinical experience in an office setting.

PMID- 9773283
TI  - The difficult teaching situation.

PMID- 9773284
TI  - The quarterback drops back for a grande plie.

PMID- 9773285
TI  - Entry of US medical school graduates into family practice residencies: 1997-1998
      and 3-year summary.
AB  - This is the 17th report prepared by the American Academy of Family Physicians
      (AAFP) on the percentage of each US medical school's graduates entering family
      practice residency programs. Approximately 16.6% of the 15,894 graduates of US
      medical schools between July 1996 and June 1997 were first-year family practice
      residents in October 1997, compared with 15.9% in 1996 and 14.6% in 1995. This is
      the highest percentage since this series of studies began in 1980-1981 (12.8%).
      Medical school graduates from publicly funded medical schools were almost twice
      as likely to be first-year family practice residents in October 1997 than were
      residents from privately funded schools, 19.8% compared with 11.8%. The Mountain
      region reported the highest percentage of medical school graduates who were first
      year residents in family practice programs in October 1997 at 25.8%; the Middle
      Atlantic and New England regions reported the lowest percentages at 11.7% and
      10.7%, respectively. Nearly half of the medical school graduates (48.1%) entering
      a family practice residency program as first-year residents in October 1997
      entered a program in the same state where they graduated from medical school. The
      percentages for each medical school have varied substantially from year to year
      since the AAFP began reporting this information. This article reports the average
      percentage for each medical school for the last 3 years. Also reported are the
      number and percentage of graduates of colleges of osteopathic medicine who
      entered Accreditation Council for Graduate Medical Education-accredited family
      practice residency programs, based on estimates provided by the American
      Association of Colleges of Osteopathic Medicine.

PMID- 9773286
TI  - Results of the 1998 National Resident Matching Program: family practice.
AB  - The 1998 National Resident Matching Program (NRMP) results reflect a change in
      the perceptions and choices of physicians entering graduate medical education in
      the United States. Ninety-one fewer positions were filled in family practice
      residency programs in 1998, as well as 21 fewer in primary care internal
      medicine, 12 fewer in primary care pediatrics, and 13 fewer in internal medicine
      pediatric programs. In contrast, 49 more positions were filled in anesthesiology,
      and 12 more US seniors chose diagnostic radiology, two "marker" disciplines that
      have recently been market sensitive. Thirty-four more positions were also filled
      in each of categorical internal medicine and pediatrics programs, where trainees
      are "pluripotential" with perceived options for practicing as generalists or
      entering subspecialty fellowships, depending on the market. While the demands of
      managed care and the needs of rural and underserved populations continue to offer
      a market for family physicians, family practice may have experienced a "primary
      care backlash" though the 1998 NRMP.

PMID- 9773287
TI  - Family practice night-call frequency: 1981-1997.
AB  - BACKGROUND AND OBJECTIVES: Night call has both service and educational value.
      This study examined trends in night-call frequency from 1981-1997. Our hypothesis
      was that night-call frequency is decreasing in family practice residency
      programs. METHODS: We reviewed the Directory of Family Practice Residency
      Programs from 1981, 1989, and 1997 and entered into a database information about
      call frequency from all of the programs in each year. In-house night-call
      frequency and frequency of home call requiring other trips to the hospital were
      combined to determine total calls per year. RESULTS: The mean number of total
      calls for PGY-1 residents was 190, 124, and 104 for each cohort year,
      respectively (1981, 1989, 1997). PGY-2 total calls were 160, 96, and 74. PGY-3
      total calls were 151, 73, and 57. For all years of residency, total calls in 1997
      were fewer than for 1981 and 1989. CONCLUSIONS: Family practice residents have
      less night call now than in 1981 or 1989. The educational consequences of
      decreasing night call should be evaluated.

PMID- 9773289
TI  - Graphical methods for detecting bias in meta-analysis.
AB  - The trustworthiness of meta-analysis, a set of techniques used to quantitatively
      combine results from different studies, has recently been questioned. Problems
      with meta-analysis stem from bias in selecting studies to include in a meta
      analysis and from combining study results when it is inappropriate to do so.
      Simple graphical techniques address these problems but are infrequently applied.
      Funnel plots display the relationship of effect size versus sample size and help
      determine whether there is likely to have been selection bias in including
      studies in the meta-analysis. The L'Abbe plot displays the outcomes in both the
      treatment and control groups of included studies and helps to decide whether the
      studies are too heterogeneous to appropriately combine into a single measure of
      effect.

PMID- 9773288
TI  - Family practice in the new South Africa.
AB  - Remarkable changes are taking place in the new South Africa. Planned changes in
      the health care arena present the new, relatively small discipline* of family
      practice with great opportunity for development and growth. With established
      generalist roots and recent formal recognition in South Africa, family practice
      should be well suited for a lead role in the government's efforts to extend
      health care access to those denied it under apartheid. Whether family practice
      moves into that role will depend on whether as a discipline it can project a
      vision of how it can meet the country's health care needs. Close examination of
      family practice in South Africa shows how the field reflects many of the societal
      problems of the past and the challenges of the future. With a clear vision of its
      role in the new South Africa, family practice could overcome these challenges, as
      well as answer a broader question about the place of family practice outside of
      the first world setting.

PMID- 9773290
TI  - A closer look at confounding.
AB  - BACKGROUND AND OBJECTIVES: Confounding is one of the most common and important
      biases in primary care research. This article explains the genesis and effects of
      two common misconceptions of confounding: 1) Confounding can be assessed with a
      statistical test. 2) All covariates should be included in a multivariate model to
      control confounding. Assessment of confounding by testing the statistical
      significance of baseline differences or the significance of a potential
      confounding factor in a multivariate model can produce underestimates or
      overestimates of the true association between an exposure and an outcome.
      Inclusion of all covariates in a multivariate model may lead to controlling for
      variables that are not, in fact, confounders. This may produce underestimates or
      overestimates of the effect in question, as well as artificially widened
      confidence intervals. Both of these misconceptions can lead to profound
      misinterpretation of research results. To prevent problems resulting from these
      misunderstandings, researchers should consider drawing causal models prior to
      conducting the research and use the change-in-estimate criterion, rather than a
      statistical test, to detect confounding.

PMID- 9773291
TI  - The family physician: what sort of person?
AB  - BACKGROUND: Character and virtue are as important as knowledge and skills in
      describing the ideal family physician. Sir Luke Fildes' The Doctor, a widely
      reproduced painting, provides a visual icon that helps focus attention on
      important aspects of the character of a "healing sort of person." By stressing
      rules and principles to the detriment of a good life as a biographical or
      narrative whole, modern teaching of medical ethics may fail to sufficiently
      address this aspect of humanism in medicine. Three virtues or character traits
      that seem necessary for the ideal family physician are humility, compassion, and
      forgiveness. Such evidence as now exists supports the idea that these physician
      attributes might be linked to superior health outcomes.

PMID- 9773292
TI  - Family practice in Nepal: an international perspective.

PMID- 9773293
TI  - Apoptosis and some of its medical implications.
AB  - The following phases of apoptosis were proposed: decisive, executive and
      degradation. At least two checkpoints are recognized in the process of apoptosis:
      the p53 and Bcl-2/Bax protein family checkpoint and the protease-caspase and
      serine protease checkpoint. Signals to apoptosis from outside of the cell
      including Fas and Fas ligand interaction and sphingomyelin cycle were presented.
      Cellular morphological events in apoptosis: DNA chain breaks, changes in cell
      membrane and mitochondrial membranes were discussed. Some medical problems of
      cardiology in which apoptosis plays an important role were presented. The cancer
      treatment results depending on apoptosis of cancer cells were discussed as well.

PMID- 9773294
TI  - Antiserum against connexin32 fragment reacts with a 32-kD protein localised in
      gap junctions of mouse and rat liver, endometrium and in the fish heart.
AB  - The expression of various connexins so far identified is metabolically and
      developmentally regulated. Examples include uterine endometrium where the
      expression of gap junction protein, connexin32 (Cx32) is regulated by steroid
      hormones. In this study we attempted to synthesise a short peptide which matches
      the portion of the amino acid sequence of the Cx32. Cx32 has primary structure
      predicted from the nucleotide sequence of cDNA clone. A fragment of Cx32 molecule
      was synthesised to produce anti-peptide antibody for detecting gap junction
      protein in mouse and rat liver and endometrium. The 12-peptide, plus Abu residue
      that corresponds to residues 108-119 (LEGHGDPLHLEE-Abu) of the rat Cx32 (283-mer)
      was synthesised by the solid phase method. Antibodies against this peptide were
      raised in rabbits, screened for reactivity and specificity using dot blot assays
      [15] and used for immunocytochemical staining at the light and at electron
      microscope levels. The antibodies also reacted with fish heart myocardium.

PMID- 9773295
TI  - Expression of CD56/N-CAM antigen and some other adhesion molecules in various
      human endocrine glands.
AB  - CD56/N-CAM antigen, 140 kDa isoform of neural cell adhesion molecule (N-CAM) has
      been previously traced by some of us in follicular epithelium of human thyroid by
      immunohistochemistry. The reaction product was cell membrane bound, being
      stronger in hyperactive thyroid as compared to colloid goiter. In the current
      study, CD56 was searched in other endocrine glands and their tumors including
      parathyroids, adrenal cortex and parafollicular C cells of the thyroid (TT cell
      line). The antigen was also examined in the tissue extracts of endocrine and
      nonendocrine organs by dot blot immunoassay and anti CD56 monoclonal antibody.
      Besides, some other cell adhesion molecules (CAMs) were looked for in the tissues
      and cells tested. It has been found that CD56 is expressed in all zones of
      adrenal cortex, albeit in various intensity. The reaction was cell membrane bound
      in cortical hyperplasia and adenoma but cytoplasmic in the carcinoma of adrenal
      cortex. Other endocrine tissues and cells tested were devoid of CD56. Presence of
      CD56 antigen could be confirmed by dot blot assay with 3M KCl and NP40 extracts
      of both, thyroid and adrenal glands. Apart from CD56 some other CAMs could be
      traced in thyroid cell membranes including CD44, VLA-3 integrin and E-cadherin,
      what was not the case in the adrenal cortex. In parathyroids and parathyroid
      adenoma, diffuse immunostaining of E-cadherin and irregular, focal expression of
      CD44 was observed. These results show, apart from CD56, abundance of other CAMs
      in the thyroid gland and their relative scarcity in other endocrine tissues
      tested.

PMID- 9773296
TI  - Immunohistochemical detection of p53--effect of fixation and methods of antigen
      retrieval.
AB  - Immunohistochemical detection of p53 in paraffin-embedded biopsy specimens has
      important diagnostic, prognostic and therapeutic applications. In this study the
      influence of four different methods of fixation on immunohistochemical staining
      have been investigated in breast tumor specimens. The application of antigen
      retrieval methods was examined and the results of two different methods of
      antigen unmasking were compared. Optimal results were obtained using samples
      fixed in 70% ethanol and Carnoy solution. Tissues fixed in neutral buffered
      formalin or Bouin solution required preliminary procedures for antigen unmasking.
      The technique of microwave antigen retrieval gave crisp, clear
      immunohistochemical staining for p53 in tissues fixed in neutral buffered
      formalin or Bouin solution. In conclusion, the findings in this study show that:
      1. The most suitable fixatives for immunohistochemical detection of p53 are 70%
      ethanol and Carnoy solution. 2. Antigen retrieval procedures by microwave
      irradiation are recommended for tissues fixed in 10% neutral buffered formalin or
      in Bouin solution; this pre-treatment improves the quality of the
      immunohistochemical reaction and decreases the possibility of false negative
      results. 3. The cytoplasmic accumulation of p53 should be accepted as a fact, not
      as a result of poor fixation and should be assessed in parallel with the nuclear
      reaction.

PMID- 9773297
TI  - Flow cytometric analysis of DNA ploidy and proliferative potential in brain
      tumours.
AB  - The proliferative potential and DNA ploidy in 203 brain tumours (27 astrocytomas
      grade I, 37 grade II, 80 grade III, and 59 grade IV) were investigated using
      bromodeoxyuridine (BrdUrd) incorporation and flow cytometry. One to three tumour
      samples from each patient were incubated in vitro for one hour at 37 degrees C
      with bromodeoxyuridine (BrdUrd) using the high preasure oxygen method. After
      incubation, fixation and staining, the cell preparations were analysed by flow
      cytometry. The percentage of BrdUrd-labelled cells (BrdUrd Labelling Index,
      BrdUrdLI), the predicted potential doubling time (predTpot) and the total DNA
      content were evaluated. The percentage of unlabelled S-phase cells (SPF) and
      proliferative index (PI, the percentage of cells in S + G2 phases) were also
      estimated. DNA aneuploidy was found in 61.1% of high-grade (III-IV) and 50.0% of
      low-grade (I-II) astrocytomas. The tumours showed variability in the BrdUrdLI
      values which ranged from 0.2 to 15.8%. Significantly higher mean value for
      BrdUrdLI was shown in grade III-IV astrocytomas (3.4%), than in grade I-II
      astrocytomas (1.5%), p = 0.0068. Also significantly shorter mean predTpot was
      shown in high grade III-IV astrocytomas (28 days) than in low grade I-II tumours
      (51 days), p = 0.0096. However, no relationship was shown between other cell
      proliferation parameters and histological grade. The mean intratumoral
      variability calculated on the basis of BrdUrdLI values on 2-3 samples from each
      tumour amounted to 31.2% +/- SD 15.9%.

PMID- 9773298
TI  - Aortic root replacement: twenty years of experience.
AB  - BACKGROUND: Aortic root replacement is a complex surgical procedure which has
      undergone major technical modifications with time. In order to assess the early
      and long-term outcome after aortic root replacement with this procedure, our
      entire experience of a two decade period was reviewed. METHODS: Between January
      1979 and March 1997, 156 aortic root replacement operations were performed. One
      hundred and twenty five patients (80%) were male and 31 female; their mean age
      was 50 +/- 16 years. Diagnosis was annuloaortic ectasia in 79 patients, aortic
      dissection in 51 (acute 22, chronic 29), isolated aortic valve pathology in 24
      and aneurysm of sinus of Valsalva in 5. Thirty nine patients had aortic root
      replacement using the standard "Bentall" technique, 73 using the "modified
      Bentall" technique, 15 using the Cabrol technique. Biologic substitutes of the
      aortic root were used in 29 patients (19 autografts, 4 homografts, 6 xenografts).
      Mean follow-up time was 41 +/- 40 months (range 1 month-18 years). RESULTS: There
      were 12 (7.6%) hospital deaths. Hospital mortality in elective cases was 5%
      (7/134) and 22% (5/22) in emergent (p = 0.01). A trend toward reduced early
      mortality was demonstrated in recent years. Mortality was 5% for the "modified
      Bentall" group, 3% for the "Biologic root" group, 10% for the "Bentall" group and
      20% for the "Cabrol" group. Hospital mortality was significant higher in "Cabrol"
      group than in "modified Bentall" group (p = 0.04). The overall long-term survival
      rate was 78 +/- 4% at 5 years, 71 +/- 6% at 10 years and 51 +/- 13% at 15 years.
      No significant difference in survival rate nor freedom from complications was
      observed among patient groups. Need for reoperation and valve-related adverse
      events become prevalent after 10 years of follow-up. CONCLUSION: The decrease in
      early mortality and the satisfying late results demonstrate that aortic root
      replacement is a low risk surgical procedure and an effective and durable
      treatment. The availability of biologic substitutes for the aortic root has
      allowed the extension of this operation to all patient age group, with results
      comparable to these obtained with composite grafts.

PMID- 9773299
TI  - Dipyridamole stress echocardiography and exercise testing for risk stratification
      after uncomplicated myocardial infarction.
AB  - BACKGROUND: Risk stratification for subsequent cardiac events after an acute
      infarction can be obtained by exercise testing or dipyridamole stress
      echocardiography. It remains to be determined whether these modalities are
      equivalent and provide incremental information on top of clinical evaluation. The
      aim of our study was to compare the prognostic information obtained early after
      an acute uncomplicated myocardial infarction of high dose dipyridamole coupled
      with echocardiography (stress echo) or maximal symptom-limited exercise testing.
      METHODS AND RESULTS: Ninety patients underwent dipyridamole stress echo and
      exercise testing at a mean +/- SD of 9 +/- 4 days after admission for acute
      uncomplicated first myocardial infarction. All patients were prospectively
      followed for 22 +/- 16 months. There were 9 hard events (3 cardiac deaths and 6
      acute myocardial infarctions) and 12 soft events due to post MI angina (6
      angioplasty and 6 bypass surgery procedures). Univariate predictor of hard events
      was rest-stress wall motion score index variation (p = 0.009); univariate
      predictors of all events (hard + soft) were: positive exercise testing (p =
      0.001), positive stress echo (p = 0.001), rest-stress wall motion score index
      variation (p = 0.002), extent of ischemia at echo (p = 0.008). Multivariate
      analysis by Cox selected a non-Q wave infarction and rest-stress wall motion
      score index variation as predictors of death or reinfarction (overall chi-square
      for the model 12.2, p = 0.0022). CONCLUSIONS: Stress echo is superior to
      ergometric variables for predicting events after uncomplicated myocardial
      infarction.

PMID- 9773300
TI  - Control of hypertension in Italy: results of the "Study on Antihypertensive
      Treatment in General Practice (STAP)". Physicians Taking Part in STAP.
AB  - BACKGROUND: Various epidemiological surveys from different countries have
      documented the unsatisfactory control of arterial hypertension. The aim of this
      study was to assess the current status of treatment and control of hypertension
      in Italy. METHODS: A random sample of general practitioners (GP) working in
      several Aziende Sanitarie Locali (Local health offices-ASL) throughout Italy were
      invited to take part in the study. Each doctor had to recruit a random sample of
      15-20 hypertensive patients receiving antihypertensive drugs among those
      attending his/her office for any reason. A standard medical history, specifically
      oriented to hypertension and its pharmacological treatment, was taken for each
      patient. Three blood pressure (BP) measurements were made, with the patient
      seated for at least 5 minutes, using an accurate automatic device (A&D UA-732),
      and the mean was taken as each patient's BP. RESULTS: A total of 73 GPs (17% of
      the invited sample), working in 14 Italian ASL (six in the north of the country,
      four in the center and four in the south and islands), agreed to participate in
      the study. They recruited an average of 17 patients each, for a total of 1204
      hypertensive subjects (663 women and 541 men) 633 of whom were 65 years old or
      more, mean age 64 +/- 11 years, range 25-94 years. More than half (56%) had been
      taking antihypertensive drugs for at least five years; 42% were taking one drug,
      40% two, 16% three and 2% four drugs. Respectively, 63% and 23% had systolic BP
      (SBP) > or = 140 and > or = 160 mmHg; 28% and 14% had diastolic BP (DBP) > or =
      90 and 95 mmHg. In 71%, BP was < 160/95 mmHg, but only 33% had BP lower than
      140/90 mmHg. BP control was similar in males and females, but worse in the
      elderly. Nine percent of patients complained of symptomatic side effects, usually
      mild. Only 8% admitted to poor compliance with the antihypertensive therapy, and
      their BP was significantly less well controlled. CONCLUSIONS: Control of BP in
      patients receiving antihypertensive drugs is still far from optimal in Italy,
      just as in other countries. This situation seems more related to the fact that
      doctors do not tackle the problem aggressively, than to the patients' degree of
      compliance with therapy.

PMID- 9773301
TI  - Transradial approach for coronary procedures: initial experience and results.
AB  - BACKGROUND: Due to the recent miniaturization of angioplasty equipment, the
      transradial approach has gained favor as an alternative catheterization method
      for coronary procedures. The purpose of this study was to assess the practical
      clinical application of this method. METHODS: Between June 1997 and February
      1998, one operator (MG) attempted the percutaneous transradial approach in 185
      consecutive unselected patients with functional radial arch attested using
      Allen's test. In this series of patients, 102 interventional procedures, balloon
      angioplasty including stent implantation, were performed with 6F or 7F guiding
      catheters. RESULTS: Radial arterial punctures for diagnostic procedures were
      performed in 179 patients with a success rate of 97%. In the six failed
      transradial accesses, the procedure was performed via the transfemoral route.
      Balloon angioplasty was performed in 29 patients, 28% (33 lesions), PTCA and
      stent implantation were performed in 73 patients, 72% (80 lesions). Procedural
      success was achieved in 100 (98.2%). Two PTCA failed due to the impossibility of
      crossing a total occlusion. During hospitalization, one patient died of unstable
      angina and poor left ventricular function 7 days after stenting without stent
      occlusion at angiography. No major complications related to entry site were
      observed, and no patients required vascular surgery or blood transfusions.
      CONCLUSION: This preliminary experience suggests that coronary procedures can be
      performed safely using the transradial approach. Access-site complications are
      virtually eliminated and early ambulation may result in a shortened hospital stay
      and lower hospital costs.

PMID- 9773302
TI  - [Emergency coronary surgery after failed angioplasty: 11 years of experience
      (1987-1997)].
AB  - METHODS: From January 1987 to December 1997, thirty patients underwent emergent
      or urgent coronary artery bypass grafting after failed elective percutaneous
      transluminal coronary angioplasty. Dissection/occlusion of the target artery was
      the commonest complication, but we also had two cases of stent dislocation and
      one case of coronary artery wall perforation. Two-thirds of the patients
      experienced extreme preoperatory hemodynamic instability (i.e., cardiac arrest or
      cardiogenic shock) and half had to be intubated in the Catheterization
      Laboratory. An average of 1.73 grafts/patient was performed. Complete coronary
      revascularization was achieved in 93% of the cases; the internal mammary artery
      could be employed in one-third only. RESULTS: In-hospital mortality was 10%, and
      perioperatory myocardial infarction or persistent ischemia could be detected in
      half of the patients. The need for aortic counterpulsation, and the use of
      inotropic and antiarrhythmic drugs were higher than average in this group of
      patients; while intensive care unit and hospital stay were longer. Patients with
      deteriorated preoperative hemodynamics fared significantly worse. Late results
      were encouraging: seventy-five per cent of all patients (and 84% of hospital
      survivors) were still alive an average of 52 months after surgery. Two-thirds of
      all patients (and 72% of hospital survivors) were alive and angina-free.
      CONCLUSIONS: Even in the current era, revascularization surgery after failed
      coronary angioplasty still carries an increased risk for postoperative
      complications and death, especially for patients with deteriorated preoperative
      hemodynamic conditions. On the other hand, postoperative middle- and long-term
      results are encouraging, as hospital survivors were similar to elective bypass
      patients regarding survival and freedom from return of angina.

PMID- 9773303
TI  - [Primary angioplasty in acute inferior myocardial infarct with anterior ST
      segment depression: the long-term follow-up].
AB  - BACKGROUND: Concomitant anterior ST-segment depression is a marker of severe
      prognosis in inferior myocardial infarction. PATIENTS AND METHODS: Prospective
      observational study in patients with inferior acute myocardial infarction and ST
      segment depression > or = 4 mm in the anterior leads, who were treated with
      primary angioplasty. Angiography was performed at hospital discharge and at six
      months, and a clinical follow-up was obtained at one year after the infarction.
      RESULTS: Sixty-three patients were included in the study. Pre-hospital and in
      hospital delay were 147 +/- 70 minutes (20-355) and 54 +/- 11 minutes (18-80),
      respectively. Angioplasty was successful in all patients and 48 stents were
      implanted in 36 patients (57%). Angiography was performed at hospital discharge
      in 55 patients (87%) and showed a TIMI grade 3 coronary flow in the infarct
      related artery in all cases. The left ventricular ejection fraction was 0.55 +/-
      0.09 (0.4-0.8). One patient (1.6%) died before discharge, two (3.2%) had ischemic
      complications (one had non-fatal reinfarction, another had recurrent angina at
      rest), and three (4.9%) had local vascular complications. At the six-month follow
      up, none of the patients had died. One had suffered reinfarction (1.6%) and
      another had been readmitted for recurrence of angina at rest (1.6%); none had
      symptoms of stable angina. The ejection fraction was 0.56 +/- 0.12 and eight
      patients (14%) showed angiographic restenosis. At twelve months, two patients had
      died (1.6%) and five (8%) had required readmission to hospital. CONCLUSIONS:
      Primary angioplasty yielded favorable results in this group of patients. Our data
      confirm the efficacy of primary angioplasty for the treatment of acute myocardial
      infarction, with a low rate of clinical (3.2%) and angiographic (14%) restenosis
      at six months, and a high rate (87%) of event-free survival at one year follow
      up.

PMID- 9773304
TI  - [The efficacy of high- and low-energy intracavitary cardioversion in chronic
      atrial fibrillation refractory to transthoracic cardioversion].
AB  - BACKGROUND: The purpose of our study was to evaluate the efficacy and safety of
      intracavitary cardioversion (IC) with either high (HEIC) or low (LEIC) energy in
      patients with chronic atrial fibrillation (AF) refractory to external
      cardioversion. METHODS: Forty patients underwent IC with either high (30 pts) or
      low energy (10 pts); HEIC was performed by delivering one or more shocks between
      one electrode of the lead positioned in the right atrium and a back plate. The
      following energy values were used in sequence: 100, 200, 300 joules. In LEIC
      shocks were delivered between two custom-made decapolar leads (one in the
      coronary sinus and another one in the right lateral atrial wall) beginning from
      50 Volts and increasing the voltage by steps of 50 Volts. Another catheter in the
      right ventricular apex was used for ventricular synchronization. RESULTS: Sinus
      rhythm was restored in 24/30 (80%) patients undergoing HEIC and in 10/10 (100%)
      patients undergoing LEIC. No serious or permanent complications occurred.
      CONCLUSIONS: HEIC and LEIC are effective in patients with AF refractory to
      external cardioversion. Both the procedures seem to be safe.

PMID- 9773305
TI  - [Coronary lesion with an aneurysm: their correction via angioplasty and the
      implantation of a coated stent].
AB  - We describe the good angiographic results obtained using a new polymeric
      prosthesis combining a stent with expandable polytetrafluoroethylene (PTFE) graft
      material in the treatment of proximal left descending coronary artery stenosis
      complicated by the presence of a coronary aneurysm.

PMID- 9773306
TI  - [Percutaneous mitral and aortic valve dilatation in the same session].
AB  - Percutaneous balloon valvuloplasty is used successfully for mitral and aortic
      rheumatic stenosis. Its application is limited in elderly degenerative aortic
      stenosis because of its poor long-term results. It is thus indicated only in
      selected groups of patients at high surgical risk. We describe three cases
      affected with mitral and aortic stenosis who underwent simultaneous mitral and
      aortic percutaneous balloon valvuloplasty. Etiology was rheumatic in the first
      two cases, while it was rheumatic and degenerative in the third case. Immediately
      after the procedure, mitral and aortic gradients decreased, with a simultaneous
      increment in aortic and mitral areas and cardiac index. There were no major
      complications. The follow-up after seven years revealed the persistence of
      relatively good results in the first two cases affected with rheumatic
      valvulopathies. In the last case, restenosis recurred a few years after the
      procedure.

PMID- 9773307
TI  - [The role of calcium antagonists in the therapy of congestive heart failure].

PMID- 9773308
TI  - [What role does pharmacological therapy have in hyperkinetic ventricular
      arrhythmias?].

PMID- 9773309
TI  - Thromboembolism floating through 3 cavities.

PMID- 9773310
TI  - Functional outcome after myocardial revascularization in ischemic left
      ventricular failure.
AB  - BACKGROUND: Myocardial revascularization in patients with left ventricular
      failure (ejection fraction < 30%) offers survival comparable to heart
      transplantation. The functional outcome, however, has yet to be determined. In
      order to assess the clinical results in patients with LVEF < 30% undergoing
      coronary artery bypass grafts (CABG), 101 consecutive patients operated between
      1/91 and 1/97 were reviewed retrospectively. METHODS: The patients were
      stratified according to presentation: 65 pts had angina (Group 1) and 36
      congestive failure (Group 2). Mean age (62 +/- 7 vs 60 +/- 8 yrs), sex (90 vs 88%
      male), LVEF (0.28 +/- 0.04 vs 0.29 +/- 0.04), prior myocardial infarction (1.2 +/
      0.4 vs 1.2 +/- 0.5 episodes/pt), presence of vital myocardium at scintiscan or
      low-dose dobutamine echocardiography (92 vs 93%), need for preoperative IABP (3.1
      vs 8.3%), aortic cross-clamp (53 +/- 21 vs 60 +/- 21 min) and cardiopulmonary
      bypass (104 +/- 31 vs 114 +/- 36 min) times were comparable. RESULTS: There was
      only 1 (1%) perioperative death due to low-output syndrome. Eleven pts (6 vs 5,
      Group 1 vs Group 2) had postoperative low-output syndrome, requiring IABP in 7
      pts (4 vs 3). There were 14 (10 vs 4, Group 1 vs Group 2) deaths during follow-up
      (29 +/- 19 months, range 2-67), with an overall actuarial survival of 91 +/- 4 vs
      100% at 1 yr and 74 +/- 9 vs 78 +/- 10% at 5 yrs in Group 1 vs Group 2,
      respectively (p = ns). Actuarial symptom-free survival was 89 +/- 4 vs 84 +/- 6%
      at 1 yr and 49 +/- 9 vs 28 +/- 11% at 5 yrs, respectively (p = 0.05). Despite the
      high recurrence of congestive failure (22 vs 66% in Group 1 vs Group 2, p =
      0.004), improvement in functional class (3.1 +/- 0.8 vs 1.5 +/- 0.7 in Group 1
      and 2.7 +/- 0.7 vs 1.8 +/- 0.5 in Group 2) and LVEF (0.28 +/- 0.04 vs 0.38 +/-
      0.04 in Group 1 and 0.29 +/- 0.04 vs 0.40 +/- 0.06 in Group 2) was found in both
      groups at follow-up. CONCLUSIONS: In spite of improving early and late survival
      after revascularization for ischemic left ventricular failure, patients
      presenting with congestive failure have an unsatisfactory symptom-free survival.
      Further studies are necessary to ascertain the relative indications to
      revascularization or transplantation in this specific patient subgroup.

PMID- 9773311
TI  - Muscle oxygenation kinetics measured by near-infrared spectroscopy during
      recovery from exercise in chronic heart failure.
AB  - The aim of the present study was to determine the kinetics of recovery of muscle
      oxygenation (MO) from comparable levels of exercise in chronic heart failure
      (CHF) patients and normal subjects and to relate MO kinetics to the level of
      exercise intolerance. The rationale is based on the observation that the O2 debt
      is increased in patients with heart failure and repayment of the debt is
      relatively slow. Ten patients with stable CHF (mean age 47 +/- 10 years) and nine
      healthy control subjects (47 +/- 6 years) were studied. All patients had ischemic
      cardiomyopathy (ejection fraction 33 +/- 7%). On different days, all subjects
      performed an upright incremental cycle ergometer exercise test with gas-exchange
      analysis to determine peak VO2, and a 6-minute constant work-rate (CWR) protocol
      at 60% of peak VO2. Oxygenation of the vastus lateralis muscle was continuously
      monitored during exercise and recovery using near-infrared spectroscopy (NIRS).
      Both MO and VO2 responses to recovery were described by a monoexponential model
      with a time delay. The time constant and time delay were combined to calculate a
      mean response time (MRT). Recovery VO2 and MO MRTs for the incremental and
      constant work rate exercise test were longer in CHF patients than in control
      subjects (p < 0.05). Both VO2 and MO MRTs were inversely related to peak VO2 (r =
      -0.73 and -0.52, respectively; p < 0.05 for both). However, both kinetics were
      not significantly different within each group between the two exercise
      intensities. In conclusion, the greater the cardiac dysfunction, as assessed by
      peak VO2, the more the recovery of muscle and total body oxygenation from both
      maximal and submaximal exercise is delayed.

PMID- 9773312
TI  - [Mitral valvuloplasty in pregnancy: a report of 4 cases].
AB  - Normal gestation is associated with adaptative cardiovascular changes. Pregnant
      women with mitral stenosis may be unable to tolerate these changes despite
      optimal medical therapy, and life-threatening complications can occur.
      Commissurotomy or valve replacement during gestation are very high-risk
      procedures both for mother and fetus. Percutaneous valvuloplasty is a valid
      alternative to cardiac surgery. In this study, we describe four pregnant women
      with mild or severe mitral stenosis who underwent percutaneous valvuloplasty
      after the first trimester of gestation. Despite tailored medical therapy with
      diuretics and beta blockers, all patients were symptomatic: NYHA class II in two
      cases, and class III in the last two. In order to protect the fetus from
      radiation, the patient's pelvic-abdominal area was shielded and left
      ventriculography was not performed. Fluoroscopy time was 7 +/- 3 min. No major
      immediate complications were observed after the procedure. Mitral valve area
      (sec. Gorlin) increased from 1.05 +/- 0.08 cm2 to 2.52 +/- 0.26 cm2 and mitral
      gradient decreased from 26.7 +/- 5.7 mmHg to 8.5 +/- 3 mmHg. The four women
      delivered healthy full-term babies. At a mean follow-up of 22 +/- 8 months, all
      patients are free of symptoms, two patients with diuretics and two without
      therapy. Percutaneous valvuloplasty can be considered the treatment of choice for
      pregnant women with symptomatic mitral stenosis refractory to medical therapy.

PMID- 9773313
TI  - [The concurrent implantation of a last-generation automatic defibrillator and a 2
      chamber pacemaker].
AB  - BACKGROUND: Potentially lethal interactions between concomitantly implanted
      pacemaker and automatic first-generation cardioverter-defibrillator have been
      reported. We therefore evaluated the reliability and safety of simultaneous
      implantation of dual-chamber pacemakers with a fourth generation cardioverter
      defibrillator incorporating an improved arrhythmia detection system. METHODS:
      Concomitant implantation of an automatic cardioverter defibrillator and a dual
      chamber pacemaker was performed in four patients for malignant tachyarrhythmias
      and symptomatic bradycardia. Two Jewel 7219C and two Micro Jewel 7223 (Medtronic
      Inc.) implantable cardioverter defibrillators were connected to an endocardial
      lead (Medtronic Mod. 6936). In 2 patients with a previously implanted
      cardioverter-defibrillator, the pacemaker was connected to bipolar atrial and
      ventricular leads. In the 2 patients who already had a dual-chamber pacemaker,
      the unipolar pacing leads implanted previously were used. At the time of
      implantation of the second device, interaction testing was performed evaluating
      ventricular fibrillation detection during high-output asynchronous pacing.
      Testing for malfunctions, reprogramming or variations of pacing thresholds of the
      pacemakers after electric shocks was also carried out. Moreover, intracavitary
      signals, stimulation thresholds and electrical therapies delivered were evaluated
      during follow-up. RESULTS: During interaction testing, induced ventricular
      fibrillation was detected, with no delay, in 4/4 cases (100%). After a mean
      follow-up of 6.3 +/- 5 months (range 2-13), 5 shocks for ventricular
      fibrillation, 10 shocks for fast ventricular tachycardia and 72 antitachycardia
      pacings were delivered. All these electrical therapies were considered
      appropriate. No symptomatic sustained tachyarrhythmia remained undetected.
      CONCLUSIONS: These data suggest that concomitant implantation of a fourth
      generation automatic cardioverter-defibrillator and a dual-chamber pacemaker
      using either unipolar or bipolar leads can be performed safely. Extreme caution
      and rigorous interactions testing is nevertheless advised when considering this
      device combination.

PMID- 9773314
TI  - [The hemodynamics laboratory without cine film. A comparison between the
      production costs of 35-mm film and the recordable compact disk].
AB  - BACKGROUND: For more than 35 years, cine film has been used as the standard
      recording medium for coronary angiography. At present, the DICOM and the CD-R
      format have been established as the standard media for the transport of cardiac
      angiographic images in place of cine angiographic film. The aim of the study was
      to compare the media production costs between two cardiac catheterization
      laboratories, with and without cine film. METHODS: We collected data from two
      different laboratories in the same geographic area which perform about 1000
      procedures/year, using a similar digital x-ray imaging system. In one lab, images
      are recorded on 35-mm film at 25 frames/sec. In the other one, the image support
      is based on a CD-R. For each laboratory we considered both direct patient and
      variable equipment costs. Direct patient costs in the film-lab include: cine
      film, processing chemicals, processing labor, chemical disposal, maintenance; in
      the digital lab: CD-R costs and masterization time. Equipment costs in the film
      lab include: cine camera, cine film processor and cine projector; in the filmless
      lab a DICOM formatter and a review workstation. The equipment amortization costs
      are considered over a three-year period. RESULTS: Total direct patient costs are
      90,000 lira for the film and 14,000 lira for the CD-R. Equipment costs are
      193,000,000 lira in the film-lab and 150,000,000 lira in the filmless one.
      Overall cost per patient is 154,300 lira for the cine film and 64,000 lira for
      the CD-R. CONCLUSIONS: This study shows that the media costs per patient for a
      digital DICOM CD-R format system are substantially less than for 35-mm film,
      permitting savings of more than 90,000,000 Italian lira per year in a mid-volume
      cardiac catheterization laboratory.

PMID- 9773315
TI  - Right bundle branch block, intermittent ST segment elevation and inducible
      ventricular tachycardia in an asymptomatic patient: an unusual presentation of
      the Brugada syndrome?
AB  - We describe the case of an asymptomatic 54-year-old female who underwent a
      routine electrocardiogram (ECG) in July 1997, which showed incomplete right
      bundle branch block and an important ST segment elevation with a coved fashion
      and the inversion of T waves in leads V1-V2. Her family and personal history was
      free of any cardiovascular pathology. She previously underwent a routine ECG in
      1991 and 1995, showing an incomplete right bundle branch block with a moderate ST
      segment elevation in leads V1-V2. Exercise test, 24-hour Holter ECG,
      echocardiogram and QT dispersion analysis were all normal. The heart-rate
      variability in the frequency domain revealed low vagal tone. The signal-averaged
      ECG was positive due to the presence of three criteria. The patient underwent an
      electrophysiologic study. The baseline ECG resembled the ones performed in 1991
      and 1995. Sinoatrial node and atrioventricular node were normal. The HV interval
      resulted of 62 ms. A syncopal polymorphic ventricular tachycardia (cycle length
      220 ms) interrupted by electrical defibrillation (200 J) was induced with double
      extrastimulus during pacing at a cycle length of 600 ms from the apex of the
      right ventricle. At the end of the study, one minute after a bolus of ajmaline 1
      mg/kg, an important ST segment elevation in lead V1 and a left axis deviation
      appeared. The patient began therapy with sotalol 80 mg t.i.d. and the
      electrophysiologic study was repeated three days later. A non-sustained
      polymorphic ventricular tachycardia (cycle length 200 ms) was induced with triple
      extrastimulus during pacing at a cycle length of 370 ms from the outflow tract of
      the right ventricle. On the basis of these results and as also suggested by
      recent reports, we decided to implant an Automatic Implantable Cardioverter
      Defibrillator.

PMID- 9773316
TI  - Worsening of head-up tilt test response during chronic beta-blocker therapy in
      patients treated for neurally mediated syncope.
AB  - The prognosis of patients with neurally mediated syncope and asystolic response
      at tilt test is controversial and there is no consensus regarding their
      management. Many patients seem to benefit from beta-blockers and their
      effectiveness has been assessed with repeated tilt tests in asystolic patients as
      well. However, little is known about the long-term effects of beta-blockers.
      Preliminary data and isolated reports suggest that in some cases, these agents
      may actually worsen the clinical outcome or the tilt test response. Three
      patients are described who experienced worsening of tilt test response with
      prolonged asystole (19.9, 9 and 5.5 sec respectively) during chronic treatment
      with beta-blockers in the absence of spontaneous symptoms. At discharge, one
      patient received a dual-chamber pace-maker combined with metoprolol, another one
      continued to take metoprolol and enalapril. The third patient refused any further
      medication. During follow-up (8, 11, 13 months respectively), they were symptom
      free. The clinical and prognostic significance of this response is not clear and
      needs further investigation.

PMID- 9773317
TI  - Percutaneous coronary angioplasty of radial artery conduits.
AB  - The higher long-term patency of internal mammary artery grafts has stimulated the
      search for alternative conduits in order to achieve a complete arterial
      myocardial revascularization. Percutaneous angioplasty is often the preferred
      strategy for the treatment of recurrent ischemia in patients who previously
      underwent bypass surgery, but there is limited experience in the treatment of
      arterial grafts. We describe two cases of percutaneous treatment of diseased
      radial artery (RA) grafts. In the first case, two disarticulated stents were
      deployed through an RA graft: half stent inside the anastomosis to the left
      anterior descending (LAD) artery, and half stent in the distal LAD artery.
      Diffuse spasm of the RA graft, resistant to ic nitrates, was successfully
      reversed after ic calcium antagonists. Absence of restenosis was confirmed two
      years later. In the second case, after simultaneous catheterization of both the
      left coronary artery and RA graft, two long stents were implanted in the LAD
      artery and a final "reversed" kissing-balloon dilation through the stent struts
      was performed; four months later the patient showed proximal occlusion of the LAD
      artery and the stenotic RA distal anastomosis was successfully dilated.

PMID- 9773318
TI  - [The accidental diagnosis of a left atrial myxoma in an 80-year-old female].
AB  - Left atrial myxoma is usually diagnosed in patients between the ages of 30 and 60
      and this diagnosis follows non-specific symptoms (i.e. temperature, anemia,
      weakness), and obstructive or embolic episodes. There are few cases in the
      literature of this disease in patients older than 80. We report the case of an 80
      year-old female admitted to our institute for an episode of supraventricular
      tachycardia. After successful treatment of the arrhythmia using verapamil i.v., a
      routine echocardiographic examination showed the presence of a left atrial mass,
      and its appearance suggested the diagnosis of a left atrial myxoma. A CT scan and
      a transesophageal echocardiography confirmed the diagnosis. The patient
      subsequently underwent cardiac catheterization and coronary angiography. In the
      absence of significant lesions of the coronary artery, a decision was made to
      remove the myxoma surgically, based on two considerations: the good clinical
      status of the patient and the high current risk of peripheral embolization. The
      operation was successful in removing the myxoma and the patient continues to be
      in good clinical condition.

PMID- 9773319
TI  - [Reflections on the organizational problem of care for the patient with chronic
      heart failure].

PMID- 9773320
TI  - [The long QT syndromes].

PMID- 9773321
TI  - [Ischemic cardiopathy and congestive heart failure. The central theme of the
      cardiology of the future. Reflections on certain pathogenetic fideisms and
      technological plagiarisms].

PMID- 9773323
TI  - [Apropos The Italian Journal of Cardiology].

PMID- 9773322
TI  - Totally calcified aneurysm of the left ventricle.

PMID- 9773324
TI  - [Coronary angiography after an uncomplicated infarct].

PMID- 9773325
TI  - [Systematics for mechanisms of tinnitus development].

PMID- 9773326
TI  - [Neonatal hearing screening: screening test for hearing disorders in newborn
      infants. Report on the "European Consensus Development Conference on Neonatal
      Hearing Screening", Mailand, 15-16 May 1998].

PMID- 9773327
TI  - [New knowledge about late sequelae of radiochemotherapy].

PMID- 9773328
TI  - [Deglutition disorders].
AB  - Dysphagia is related to the impairment of food passage from the mouth to the
      stomach. Globus pharyngis implies the frequent and often painful sensation of a
      lump in the throat that usually does not interfere with swallowing and may even
      be relieved by food intake. The diagnosis is based upon a careful history,
      clinical examination, endoscopy, dynamic imaging (videofluoroscopy,
      cinematography, videosonography) and electrophysiologic procedures (including
      pharyngoesophageal manometry, electromyography and pH determinations). Structural
      lesions of the cervical spine such as diffuse idiopathic skeletal hyperostosis
      are rare causes of dysphagia. Dysphagia following anterior cervical fusion as
      well as globus and dysphonia due to dysfunction of the vertebral joints are more
      likely. Symptoms with swallowing fluids indicate a neurogenic origin.
      Dyscoordinated swallowing, nasal reflux, dysphonia or general weakness may also
      occur. Chronic aspiration with respiratory compromize is the main consequence in
      a variety of neurological disorders as well as in cases of postsurgical
      dysphagia. Relaxation of the upper esophageal sphincter indicates coordinated
      muscle movement between the pharynx and esophagus. Dysfunction of the
      pharyngoesophageal segment may lead to cricopharyngeal achalasia. A dyskinetic
      sphincter commonly represents an extrapharyngeal cause: i.e., disease associated
      with gastroesophageal reflux. Disorders of the esophageal phase of deglutition
      can produce retrosternal pain, heartburn, regurgitation and vomiting, as well as
      laryngeal and respiratory signs. Esophageal motility disorders include lower
      achalasia, tumors, peptic strictures, inflammatory diseases, drug-induced ulcers,
      rings and webs. Motility disorders present with aperistaltic, spontaneous
      contractions, diffuse esophagospasm, or a hypermotile esophagus. Gastroesophageal
      reflux with esophagitis must always be excluded, especially in patients with a
      globus sensation. The multiple features of the appearance of the symptoms of
      dysphagia and globus makes multidisciplinary approach necessary in order to
      establish a diagnosis and begin effective treatment.

PMID- 9773329
TI  - [Chronic laryngeal edema as a late reaction to radiochemotherapy].
AB  - In addition to mucositis and myelotoxicity as well known early reactions after
      radiotherapy or radiochemotherapy in advanced head and neck tumors, late toxicity
      following treatment is an often underestimated problem. Between 1992 and 1995, 68
      patients with advanced oro- and hypopharyngeal tumors were treated primarily with
      accelerated concomitant boost radiochemotherapy (total dose irradiations of 66 Gy
      and carboplatin as chemotherapy). Ninety-three per cent of the patients had stage
      IV disease according to the UICC-TNM classification. Monitoring of follow-up
      included late toxicity with special attention given to laryngeal edema. In 37
      patients (54%) edema of the larynx as a late complication of radiochemotherapy
      was observed by clinical investigation and CT scan. The median onset of laryngeal
      edema was found 121 days after completion of therapy, with a median time of
      observation of 250 days. Observations in these patients demonstrated the chronic
      character of this edema. An increase in the laryngeal edema in 5 cases resulted
      in tracheostomy. Laryngeal edema in 10 patients was associated with recurrence of
      tumor. These results show that after xerostomia laryngeal edema is the main late
      toxicity in the head and neck after radiochemotherapy and should lead to further
      investigations to exclude possible recurrent tumor.

PMID- 9773330
TI  - [Measuring late electrically evoked potentials of the auditory system in cochlear
      implant patients].
AB  - The current adjustment of cochlear implant (CI) speech processors is based on a
      knowledge of the lower and upper limits (T- and C-levels) for electrical stimulus
      currents. These data are usually acquired from subjective classifications of
      individual patients. In cases with non-reliable patient responses, objective
      methods are necessary. Especially for the estimation of correct T-levels,
      auditory evoked potentials (AEP) can be applied, since they allow the
      determination of response thresholds in a frequency-specific manner. By
      determining the AEP of different latencies, late cortical responses can be
      registered almost without artifact contamination. These patients have been
      examined in 20 patients provided with 22- or 8-channel CI-systems (Nucleus or Med
      EI implants). In all cases, clear responses and clearly discernible threshold
      transitions could be detected. By making use of acoustical stimulation in a free
      sound field, subjective hearing threshold and the T-levels of electrical
      stimulation could be verified. Since late responses are generated in the primary
      auditory cortex, their assessment permits a nearly integral functional control of
      the aided hearing system. To date, no problems have occurred from maturation or
      attentional effects in either pediatric or adult patients. The applicability in
      very young children remains to be explored.

PMID- 9773331
TI  - [Histological studies of tympanic membrane rim defects in chronic otitis media
      mesotympanalis].
AB  - In the present study we investigated resected tympanic membranes taken during
      tympanoplasty. Tissue from 111 patients with chronic otitis media was analyzed
      after being embedded in paraffin and stained with hematoxylin and eosin. In 67
      patients (60%) the tympanic membrane epidermis did not extend beyond the margin
      of the perforation rim, so that no epithelial migration was observed on the inner
      side of the tympanic membrane. In 27 specimens (24%) we found an epithelial
      migration on the inner side of the tympanic membrane, but this did not extend to
      the margins of the excised tissue. In 17 tissue specimens (16%) epithelial
      migration extended to the margins of the resected tissue. Clinically, these
      patients were found to have non-functioning Eustachian tubes. The size of the
      tympanic membrane perforation was not found to impact on epithelial migration.
      However, there was a correlation between the extent of the epithelial migration
      seen in the specimens and the occurrence of a permanent tympanic membrane
      perforation after tympanoplasty. Of 17 patients with these findings, 4 (23%) had
      consistent reperforations. The tympanic membrane rims of these patients were
      completely covered with squamous epithelium. Patients with no or only little
      epithelial migration to the inner side of the tympanic membrane were found to
      have a significantly lower postoperative rate of recurrent infection and drum
      reperforation.

PMID- 9773332
TI  - [Problems and possible solutions in evaluation of dichotic discrimination tests
      for children].
AB  - Uttenweiler's dichotic discrimination test is a valuable contribution to the
      diagnosis of auditory perception disorders. With this test it is possible to
      establish whether there is a deficit in a patient's ability to discriminate
      between differing spoken signals to each ear, as shown in a study contrasting
      elementary school age children with normal hearing with children having auditory
      perception disorders. Until now only a limited comparison of test results has
      been possible, as previous test modes have required an increase in volume when
      words could not be completely distinguished. A further problem is that very
      different hearing abilities may give rise to the same test configurations. This
      study presents an alternative test method that allows a direct individual
      comparison of results. The volume of the words spoken is no longer increased when
      words are not adequately understood. In addition, a point system is introduced
      that enables a quantitative analysis of the same test performances. This new
      evaluation scale is explained on the basis of actual examples.

PMID- 9773333
TI  - [Small abnormality of the middle ear--a genetically-induced defect?].
AB  - Conductive and sensorineural hearing losses are of genetic origin in 20% to 60%
      of cases. In general, genetic abnormalities are more often expressed as a
      sensorineural hearing loss than as a conductive hearing loss. At present several
      genes for sensorineural hearing loss have been isolated. The most common
      genetically transmitted forms for isolated conductive hearing losses are
      otosclerosis and small malformations of the ossicles. To date no genes
      responsible for these deformations have been isolated. We present a family with
      four siblings having conductive hearing losses caused by ossification of the
      stapedial tendon. This finding is suggestive of an autosomal recessive
      inheritance. The early diagnosis of an hereditary conductive hearing loss
      contains the possibility for permitting normal development of speech.

PMID- 9773334
TI  - [Aneurysmal hemorrhage as a complication of paracentesis].
AB  - Aneurysms of the temporal part of the carotid artery are unusually rare. The
      literature contains only a few previous reports dealing with hemorrhage from such
      malformations. In the present case massive bleeding occurred from a right-sided
      intrapetrous aneurym after myringotomy, which was performed as treatment for
      bilateral secretory otitis media. Due to the absence of any specific symptoms and
      the masking effect of middle ear glue preoperative identification of the aneurysm
      was not possible. Subsequent angiography showed the large fusiform extension of
      the intrapetrous aneurysm as well as multiple intracranial aneurysms. Leakage
      from the aneurism was closed definitively with muscle, fascia lata and a gelatin
      resorcin-formalin-glue (Cardial). In order to apply the tissue patch the
      hypotympanic site of the aneurism was exposed using a posterior otosurgical
      approach. Due to extensive intracranial collateralization to the vertebral
      arteries bleeding persisted even after ligation of both carotid arteries.
      Temporary cardiac asystole was then induced to allow safe closure of the
      aneurysm. Following surgery the patient sustained loss of hearing in her ear and
      a partial peripheral facial palsy.

PMID- 9773335
TI  - [Painless recurrent cheek swelling. Parotid emphysema (pneumoparotis)].

PMID- 9773336
TI  - [Hypersalivation after tumor operation].

PMID- 9773337
TI  - [Diagnostic value of otoacoustic emissions. 1].

PMID- 9773338
TI  - How homologs can help to predict protein folds even though they cannot be
      predicted for individual sequences.
AB  - At present, one cannot predict the 3D structure of a protein directly from its
      sequence alone mainly because of errors in the energy estimates. However, a
      recently developed simple analytical theory (Finkelstein, 1998) shows that using
      a set of homologs (i.e., chains with numerous amino acid mutations but with equal
      3D folds) one can average the interaction energies over the homologs and predict
      their common 3D fold even when predictions for individual sequences are wrong
      because the energy parameters are known only approximately. In this work we
      verify this theoretical conclusion by computer simulations performed with
      simplified models of protein chains.

PMID- 9773339
TI  - Constructing phylogenies from quartets: elucidation of eutherian superordinal
      relationships.
AB  - In this work we present two new approaches for constructing phylogenetic trees.
      The input is a list of weighted quartets over n taxa. Each quartet is a subtree
      on four taxa, and its weight represents a confidence level for the specific
      topology. The goal is to construct a binary tree with n leaves such that the
      total weight of the satisfied quartets is maximized (an NP hard problem). The
      first approach we present is based on geometric ideas. Using semidefinite
      programming, we embed the n points on the n-dimensional unit sphere, while
      maximizing an objective function. This function depends on Euclidean distances
      between the four points and reflects the quartet topology. Given the embedding,
      we construct a binary tree by performing geometric clustering. This process is
      similar to the traditional neighbor joining, with the difference that the update
      phase retains geometric meaning: When two neighbors are joined together, their
      common ancestor is taken to be the center of mass of the original points. The
      geometric algorithm runs in poly(n) time, but there are no guarantees on the
      quality of its output. In contrast, our second algorithm is based on dynamic
      programming, and it is guaranteed to find the optimal tree (with respect to the
      given quartets). Its running time is a modest exponential, so it can be
      implemented for modest values of n. We have implemented both algorithms and ran
      them on real data for n = 15 taxa (14 mammalian orders and an outgroup taxon).
      The two resulting trees improve previously published trees and seem to be of
      biological relevance. On this dataset, the geometric algorithm produced a tree
      whose score is 98.2% of the optimal value on this input set (72.1% vs. 73.4%).
      This gives rise to the hope that the geometric approach will prove viable even
      for larger cases where the exponential, dynamic programming approach is no longer
      feasible.

PMID- 9773340
TI  - Better methods for solving parsimony and compatibility.
AB  - Evolutionary tree reconstruction is a challenging problem with important
      applications in biology and linguistics. In biology, one of the most promising
      approaches to tree reconstruction is to find the "maximum parsimony" tree, while
      in linguistics, the use of the "maximum compatibility" method has been very
      useful. However, these problems are NP-hard, and current approaches to solving
      these problems amount to heuristic searches through the space of possible tree
      topologies (a search which can, on large trees, take months to complete). In this
      paper, we present a new technique, Optimal Tree Refinement, for reconstructing
      very large trees. Our technique is motivated by recent experimental studies which
      have shown that certain polynomial time methods often return contractions of the
      true tree. We study the use of this technique in solving maximum parsimony and
      maximum compatibility, and present both hardness results and polynomial time
      algorithms.

PMID- 9773341
TI  - Hierarchical organization of molecular structure computations.
AB  - The task of computing molecular structure from combinations of experimental and
      theoretical constraints is expensive because of the large number of estimated
      parameters (the 3D coordinates of each atom) and the rugged landscape of many
      objective functions. For large molecular ensembles with multiple protein and
      nucleic acid components, the problem of maintaining tractability in structural
      computations becomes critical. A well-known strategy for solving difficult
      problems is divide-and-conquer. For molecular computations, there are two ways in
      which problems can be divided: (1) using the natural hierarchy within biological
      macromolecules (taking advantage of primary sequence, secondary structural
      subunits and tertiary structural motifs, when they are known); and (2) using the
      hierarchy that results from analyzing the distribution of structural constraints
      (providing information about which substructures are constrained to one another).
      In this paper, we show that these two hierarchies can be complementary and can
      provide information for efficient decomposition of structural computations. We
      demonstrate five methods for building such hierarchies--two automated heuristics
      that use both natural and empirical hierarchies, one knowledge-based process
      using both hierarchies, one method based on the natural hierarchy alone, and for
      completeness one random hierarchy oblivious to auxiliary information--and apply
      them to a data set for the procaryotic 30S ribosomal subunit using our
      probabilistic least squares structure estimation algorithm. We show that the
      three methods that combine natural hierarchies with empirical hierarchies create
      decompositions which increase the efficiency of computations by as much as 50
      fold. There is only half this gain when using the natural decomposition alone,
      while the random hierarchy suggests that a speedup of about five can be expected
      just by virtue of having a decomposition. Although the knowledge-based method
      performs marginally better, the automatic heuristics are easier to use, scale
      more reliably to larger problems, and can match the performance of knowledge
      based methods if provided with basic structural information.

PMID- 9773342
TI  - On the complexity of protein folding.
AB  - We show that the protein folding problem in the two-dimensional H-P model is NP
      complete.

PMID- 9773344
TI  - Homology detection via family pairwise search.
AB  - The function of an unknown biological sequence can often be accurately inferred
      by identifying sequences homologous to the original sequence. Given a query set
      of known homologs, there exist at least three general classes of techniques for
      finding additional homologs: pairwise sequence comparisons, motif analysis, and
      hidden Markov modeling. Pairwise sequence comparisons are typically employed when
      only a single query sequence is known. Hidden Markov models (HMMs), on the other
      hand, are usually trained with sets of more than 100 sequences. Motif-based
      methods fall in between these two extremes. The current work introduces a
      straightforward generalization of pairwise sequence comparison algorithms to the
      case when multiple query sequences are available. This algorithm, called Family
      Pairwise Search (FPS), combines pairwise sequence comparison scores from each
      query sequence. A BLAST implementation of FPS is compared to representative
      examples of hidden Markov modeling (HMMER) and motif modeling (MEME). The three
      techniques are compared across a wide range of protein families, using query sets
      of varying sizes. BLAST FPS significantly outperforms motif-based and HMM
      methods. Furthermore, FPS is much more efficient than the training algorithms for
      statistical models.

PMID- 9773343
TI  - Algorithmic determination of core positions in the VL and VH domains of
      immunoglobulin molecules.
AB  - We introduce a new algorithmic method for identifying the geometrical core of
      proteins that does not require the usual superposition of structures. A
      geometrical core is defined as the set of residues such that the C alpha (I) - C
      alpha (J) atom distances are identical in all structures of the protein family
      under study, where I and J are secondary structure positions in the structural
      units--strands, loops, or parts of them. The result of applying the algorithm to
      53 Ig structures leads to the identification of two geometrical core sets of C
      alpha atom positions for the VL and VH domains. Applications of the core sets are
      described.

PMID- 9773346
TI  - Estimation for restriction sites observed by optical mapping using reversible
      jump Markov Chain Monte Carlo.
AB  - A fundamentally new molecular-biology approach in constructing restriction maps,
      Optical Mapping, has been developed by Schwartz et al. (1993). Using this method
      restriction maps are constructed by measuring the relevant fluorescence intensity
      and length measurements. However, it is difficult to directly estimate the
      restriction site locations of single DNA molecules based on these optical mapping
      data because of the precision of length measurements and the unknown number of
      true restriction sites in the data. We propose the use of a hierarchical Bayes
      model based on a mixture model with normals and random noise. In this model we
      explicitly consider the missing observation structure of the data, such as the
      orientations of molecules, the allocations of cutting sites to restriction sites,
      and the indicator variables of whether observed cut sites are true or false.
      Because of the complexity of the model, the large number of missing data, and the
      unknown number of restriction sites, we use Reversible-Jump Markov Chain Monte
      Carlo (MCMC) to estimate the number and the locations of the restriction sites.
      Since there exists a high multimodality due to unknown orientations of molecules,
      we also use a combination of our MCMC approach and the flipping algorithm
      suggested by Dancik and Waterman (1997). The study is highly computer-intensive
      and the development of an efficient algorithm is required.

PMID- 9773345
TI  - Dynamic programming alignment accuracy.
AB  - Algorithms for generating alignments of biological sequences have inherent
      statistical limitations when it comes to the accuracy of the alignments they
      produce. Using simulations, we measure the accuracy of the standard global
      dynamic programming method and show that it can be reasonably well modelled by an
      "edge wander" approximation to the distribution of the optimal scoring path
      around the correct path in the vicinity of a gap. We also give a table from which
      accuracy values can be predicted for commonly used scoring schemes and sequence
      divergences (the PAM and BLOSUM series). Finally we describe how to calculate the
      expected accuracy of a given alignment, and show how this can be used to
      construct an optimal accuracy alignment algorithm which generates significantly
      more accurate alignments than standard dynamic programming methods in simulated
      experiments.

PMID- 9773347
TI  - A polyhedral approach to RNA sequence structure alignment.
AB  - Ribonucleic acid (RNA) is a polymer composed of four bases denoted A, C, G, and
      U. It generally is a single-stranded molecule where the bases form hydrogen bonds
      within the same molecule leading to structure formation. In comparing different
      homologous RNA molecules it is important to consider both the base sequence and
      the structure of the molecules. Traditional alignment algorithms can only account
      for the sequence of bases, but not for the base pairings. Considering the
      structure leads to significant computational problems because of the dependencies
      introduced by the base pairings. In this paper we address the problem of
      optimally aligning a given RNA sequence of unknown structure to one of known
      sequence and structure. We phrase the problem as an integer linear program and
      then solve it using methods from polyhedral combinatorics. In our computational
      experiments we could solve large problem instances--23S ribosomal RNA with more
      than 1400 bases--a size intractable for former algorithms.

PMID- 9773348
TI  - Optimization of protein structure on lattices using a self-consistent field
      approach.
AB  - Lattice modeling of proteins is commonly used to study the protein folding
      problem. The reduced number of possible conformations of lattice models
      enormously facilitates exploration of the conformational space. In this work, we
      suggest a method to search for the optimal lattice models that reproduced the off
      lattice structures with minimal errors in geometry and energetics. The method is
      based on the self-consistent field optimization of a combined pseudoenergy
      function that includes two force fields: an "interaction field," that drives the
      residues to optimize the chain energy, and a "geometrical field," that attracts
      the residues towards their native positions. By varying the contributions of
      these force fields in the combined pseudoenergy, one can also test the accuracy
      of potentials: the better the potentials, i.e., the more accurate the
      "interaction field," and the smaller the contribution of the "geometrical field"
      required for building accurate lattice models.

PMID- 9773349
TI  - Identifying satellites and periodic repetitions in biological sequences.
AB  - We present in this paper an algorithm for identifying satellites in DNA
      sequences. Satellites (simple, micro, or mini) are repeats in number between 30
      and as many as 1,000,000 whose lengths vary between 2 and hundreds of base pairs
      and that appear, with some mutations, in tandem along the sequence. We
      concentrate here on short to moderately long (up to 30-40 base pairs) approximate
      tandem repeats where copies may differ up to epsilon = 15-20% from a consensus
      model of the repeating unit (implying individual units may vary by 2 epsilon from
      each other). The algorithm is composed of two parts. The first one consists of a
      filter that basically eliminates all regions whose probability of containing a
      satellite is less than one in 10(4) when epsilon = 10%. The second part realizes
      an exhaustive exploration of the space of all possible models for the repeating
      units present in the sequence. It therefore has the advantage over previous work
      of being able to report a consensus model, say m, of the repeated unit as well as
      the span of the satellite. The first phase was designed for efficiency and takes
      only O (n) time where n is the length of the sequence. The second phase was
      designed for sensitivity and takes time O (n . N (e, k)) in the worst case where
      k is the length of the repeating unit m, e = [epsilon k] is the number of
      differences allowed between each repeat unit and the model m, and N (e, k) is the
      maximum number of words that are not more than e differences from another word of
      length k. That is, N (e, k) is the maximum size of an e-neighborhood of a string
      of length k. Experiments reveal the second phase to be considerably faster in
      practice than the worst-case complexity bound suggests. Finally, the present
      algorithm is easily adapted to finding tandem repeats in protein sequences, as
      well as extended to identifying mixed direct-inverse tandem repeats.

PMID- 9773350
TI  - Multiple genome rearrangement and breakpoint phylogeny.
AB  - Multiple alignment of macromolecular sequences generalizes from N = 2 to N > or =
      3 the comparison of N sequences which have diverged through the local processes
      of insertion, deletion and substitution. Gene-order sequences diverge through non
      local genome rearrangement processes such as inversion (or reversal) and
      transposition. In this paper we show which formulations of multiple alignment
      have counterparts in multiple rearrangement. Based on difficulties inherent in
      rearrangement edit-distance calculation and interpretation, we argue for the
      simpler "breakpoint analysis." Consensus-based multiple rearrangement of N > or =
      3 orders can be solved exactly through reduction to instances of the Travelling
      Salesman Problem (TSP). We propose a branch-and-bound solution to TSP
      particularly suited to these instances. Simulations show how non-uniqueness of
      the solution is attenuated with increasing numbers of data genomes. Tree-based
      multiple alignment can be achieved to a great degree of accuracy by decomposing
      the tree into a number of overlapping 3-stars centered on the non-terminal nodes,
      and solving the consensus-based problem iteratively for these nodes until
      convergence. Accuracy improves with very careful initializations at the non
      terminal nodes. The degree of non-uniqueness of solutions depends on the position
      of the node in the tree in terms of path length to the terminal vertices.

PMID- 9773351
TI  - An analysis of a class of DNA sequence reading molecules.
AB  - Linked polyamides are a class of designed molecules that bind in the minor groove
      of double-stranded DNA in a partially sequence-specific manner but have limited
      sequence discriminatory abilities. This suggests a need for design alternatives
      to create molecules with enhanced sequence specificity. In this report we present
      formal proofs of the theoretical limits of the DNA sequence specificity of
      hypothetical sequence reading molecules as a function of their base recognition
      properties and sequence content and length of their target sequence. We prove
      that molecules containing nonspecific readers at critical positions within the
      molecule may have enhanced sequence specificity over molecules composed entirely
      of base specific reading elements. We also determine optimal patterns of base
      recognition for molecules in order to optimize their target sequence specificity.
      We also examine the effect of the length of a polyamide (i.e., the number of base
      pairs it binds) on its sequence discriminatory ability and determine necessary
      concentration dependent constraints on the binding free energies in order for
      longer polyamides to have greater sequence specificity than shorter ones. We show
      that unless the discriminatory ability of a ring for its preferred base is very
      strong, longer polyamides do not necessarily have greater sequence specificity
      over shorter ones when compared at the same molar concentration.

PMID- 9773353
TI  - An efficient computational method for globally optimal threading.
AB  - Computational recognition of native-like folds of an anonymous amino acid
      sequence from a protein fold database is considered to be a promising approach to
      the three-dimensional (3D) fold prediction of the amino acid sequence. We present
      a new method for protein fold recognition through optimally aligning an amino
      acid sequence and a protein fold template (protein threading). The fitness of
      aligning an amino acid sequence with a fold template is measured by (1) the
      singleton fitness, representing the compatibility of substituting one amino acid
      by another and the combined preference of secondary structure and solvent
      accessibility for a particular amino acid, (2) the pairwise interaction,
      representing the contact preference between a pair of amino acids, and (3)
      alignment gap penalties. Though a protein threading problem so defined is known
      to be NP-hard in the most general sense, our algorithm runs efficiently if we
      place a cutoff distance on the pairwise interactions, as many of the existing
      threading programs do. For an amino acid sequence of size n and a fold template
      of size m with M core secondary structures, the algorithm finds an optimal
      alignment in O (Mn1.5C + 1 + mnC + 1) time and O (MnC + 1) space, where C is a
      (small) nonnegative integer, determined by a particular mathematical property of
      the pairwise interactions. As a case study, we have demonstrated that C is less
      than or equal to 4 for about 75% of the 293 unique folds in our protein database,
      when pairwise interactions are restricted to amino acids < or = 7 A apart
      (measured between their beta carbon atoms). An approximation scheme is developed
      for fold templates with C > 4, when threading requires too much memory and time
      to be practical on a typical workstation.

PMID- 9773352
TI  - Regression analysis of multiple protein structures.
AB  - A general framework is presented for analyzing multiple protein structures using
      statistical regression methods. The regression approach can superimpose protein
      structures rigidly or with shear. Also, this approach can superimpose multiple
      structures explicitly, without resorting to pairwise superpositions. The
      algorithm alternates between matching corresponding landmarks among the protein
      structures and superimposing these landmarks. Matching is performed using a
      robust dynamic programming technique that uses gap penalties that adapt to the
      given data. Superposition is performed using either orthogonal transformations,
      which impose the rigid-body assumption, or affine transformations, which allow
      shear. The resulting regression model of a protein family measures the amount of
      structural variability at each landmark. A variation of our algorithm permits a
      separate weight for each landmark, thereby allowing one to emphasize particular
      segments of a protein structure or to compensate for variances that differ at
      various positions in a structure. In addition, a method is introduced for finding
      an initial correspondence, by measuring the discrete curvature along each protein
      backbone. Discrete curvature also characterizes the secondary structure of a
      protein backbone, distinguishing among helical, strand, and loop regions. An
      example is presented involving a set of seven globin structures. Regression
      analysis, using both affine and orthogonal transformations, reveals that globins
      are most strongly conserved structurally in helical regions, particularly in the
      mid-regions of the E, F, and G helices.

PMID- 9773354
TI  - The neurobiology of ECT: the road taken.

PMID- 9773355
TI  - Neurochemical mechanisms of action of ECS: evidence from in vivo studies.
AB  - Recent advances in receptor pharmacology and in the understanding of
      intracellular signal-transduction systems have given rise to new theories of the
      mechanism of action of antidepressant drugs. The relevance of these theories to
      the antidepressant mechanism(s) of electroconvulsive shock (ECS) is discussed,
      with a view to increasing understanding of the mechanism of electroconvulsive
      therapy (ECT). Particular attention is given to results obtained with in vivo
      methods both in experimental animals and in human subjects.

PMID- 9773356
TI  - Neurobiological correlates of the antidepressant action of electroconvulsive
      therapy.
AB  - This article reviews the major neurobiologic effects of electroconvulsive therapy
      (ECT) implicated in its antidepressant actions. These effects are organized into
      three main groups: (1) the action of ECT on the monoamine neurotransmitter
      system, norepinephrine, serotonin, and dopamine; (2) the neurotrophic action of
      ECT; and (3) the anticonvulsant effect of ECT. This review emphasizes clinical
      studies, but relevant animal studies are used to infer more details about changes
      in neurotransmitter turnover, peptides, and changes in gene expression. There are
      significant differences in the actions of ECT compared with antidepressant
      medications, for example, on monoaminergic systems, which may explain why ECT is
      such an effective antidepressant.

PMID- 9773357
TI  - Molecular and cellular actions of chronic electroconvulsive seizures.
AB  - Recent studies have begun to examine the influence of electroconvulsive shock
      (ECS) on the expression of growth factors in brain, as well as alterations in the
      function and structure of certain populations of neurons. These studies
      demonstrate that long-term ECS increases the expression of brain-derived
      neurotrophic factor (BDNF) and its receptor, TrkB, in limbic brain regions. BDNF,
      a member of the nerve growth-factor family, has been shown to increase the
      synaptic strength, survival, and growth of adult neurons. Studies in vivo and in
      cultured cells indicate that the induction of BDNF and TrkB is mediated by the
      cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB), a
      transcription factor that is activated by cAMP and Ca2+ intracellular pathways.
      Chronic ECS is also reported to induce sprouting of hippocampal neurons, and
      studies in BDNF mutant mice indicated that this sprouting is partially dependent
      on upregulation of BDNF. Increased expression of BDNF and sprouting could also
      contribute to the altered electrophysiologic properties of hippocampal neurons.
      These effects of chronic ECS are discussed with respect to recent studies
      demonstrating that the pathophysiology of stress and depression involves atrophy
      or death of hippocampal neurons. This work has led to the hypothesis that ECS and
      antidepressant drugs, via regulation of neurotrophic factors, reverse the atrophy
      of stress-vulnerable neurons or protect these neurons from further damage.

PMID- 9773358
TI  - Magnetic stimulation of the brain in animal depression models responsive to ECS.
AB  - Studies in humans show antidepressant potential for transcranial magnetic
      stimulation (TMS). We therefore studied TMS in animal models of depression and
      compared its effects with those of ECS. ECS in rats has several robust behavioral
      effects, including enhancement of apomorphine-induced stereotypy, reduction of
      immobility time in the Porsolt swim test, and increases in seizure threshold for
      subsequent stimulation. Seven or 10 days of daily TMS consistently enhanced
      apomorphine-induced stereotypy, whereas a single session of TMS did not. Two TMS
      treatments markedly reduced immobility in the Porsolt swim test, as does ECS. A
      single TMS treatment markedly reduces the percentage of rats seizing in response
      to a ECS-like electrical stimulus to the brain 10 s later, as does an ECS
      treatment itself but not a sub-convulsive electrical stimulus to the brain. Long
      term administration of ECS as well as other antidepressant treatments
      downregulates beta-adrenergic receptors. We found that TMS significantly reduced
      the density of [3H]CGP-12177 (a radioligand with beta-adrenergic affinity)
      binding sites in cortical (p < 0.05) but not hippocampal membranes. The role of
      monoamines in the mechanism of action of antidepressant treatments was
      investigated in numerous studies. Region-specific changes in the brain steady
      state levels, and turnover rates of monoamines were detected 10 s after
      administration of a single repetitive TMS (rTMS) session. In the striatum and
      hippocampus, dopamine levels were increased by 25 +/- 1.5% and 18 +/- 0.8%,
      respectively, but were reduced in frontal cortex and decreased in the striatum
      and hippocampus in the TMS-treated rats with no change to the midbrain. TMS
      caused an increase in serotonin and 5-HIAA levels in the hippocampus but not in
      other brain regions examined in this study. The ability of TMS to induce
      behavioral and biochemical alterations similar to those of ECS may further
      support the potential role of TMS as an antidepressant treatment and bring us
      closer to the understanding of the mechanism of action of TMS.

PMID- 9773359
TI  - Genetic approaches to the neurobiology of electroconvulsive therapy.
AB  - Although electroconvulsive therapy effectively treats severe psychiatric
      disorders, its neurobiologic mechanisms are not fully understood. Also unclear is
      the basis for variability in seizure threshold and duration among patients. We
      used multiple strains of rats and mice to test for genetic variation in the
      properties of seizures induced by electroconvulsive shock (ECS). We specifically
      measured seizure duration, sensitivity to proconvulsant actions of caffeine, and
      relative refractoriness to postictal induction of further seizures, all of which
      showed significant interstrain variability. In addition, tonic-clonic seizure
      durations correlated with rates of immediate mortality, suggesting variations in
      underlying levels of cellular excitability across strains. By using quantitative
      autoradiography to relate these findings to neurobiologic mechanisms, we found
      significant correlations between hippocampal A1-receptor binding, cortical and
      striatal N-methyl-D-aspartate (NMDA)-receptor binding, and the modification of
      seizure duration by caffeine. These studies suggest that heritable factors
      modulate the neurobiologic determinants of electrically induced seizures.
      Furthermore, they suggest that genetic factors may contribute to clinically
      observed variability in seizure thresholds. Finally, the data provide a basis for
      future molecular genetic approaches to link ECS-induced changes in seizure
      properties to relevant transmitter systems.

PMID- 9773360
TI  - Safe motherhood USA.

PMID- 9773361
TI  - Systemic lupus erythematosus: perinatal and neonatal implications.
AB  - Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that can
      affect almost all organ systems in the body. It is most common in women of
      childbearing age and may cause multiple peripartum complications. This article
      reviews the pathophysiology of SLE and the effects of SLE on fertility and
      pregnancy. The complexities of managing a pregnant patient with SLE are reviewed,
      and the importance of interdisciplinary collaboration discussed, as well as the
      effects of SLE on the fetus and a review of neonatal lupus erythematosus.
      Finally, a case report of a pregnant patient with SLE with challenging clinical
      management issues is presented.

PMID- 9773362
TI  - Growth and development of a hospital-based lactation program and mother's own
      milk bank.
AB  - This article describes the development and characteristics of a hospital-based
      lactation program and mother's own milk bank in a large pediatric hospital in the
      southwestern United States. Professional and technical staffing, physical space
      of the milk bank area, and the program's services and special features are
      outlined. Quality control issues about human milk preparation, fortification,
      storage, and transport are discussed.

PMID- 9773363
TI  - Newborn predictors of infant irritability.
AB  - OBJECTIVE: To identify newborn infant behaviors that may predict infant
      irritability, commonly referred to as colic. DESIGN: A prospective, correlational
      design, with data collection occurring the first 4 days of life and again at 1
      month of age. SETTING: This study was conducted in a private hospital in a large
      metropolitan city in the Midwest. PARTICIPANTS: Sixty infants who were at low
      risk and full term and whose weight was appropriate for gestational age were
      recruited during their postpartum hospital stay. Infants with congenital
      anomalies, signs of illness, or high-risk factors were excluded from the study.
      MAIN OUTCOME MEASURES: During infants' 1-4-day hospital stays, their crying was
      assessed and reported by the nurses, and a Neonatal Behavioral Assessment Scale
      was completed on each infant. At 1 month of age, irritability was measured using
      the Fussiness Rating Scale. RESULTS: Only two components of the Neonatal
      Behavioral Assessment Scale were related to development of colic or infant
      irritability at 1 month of age. These were the cluster of variables representing
      motor activity and the Neonatal Behavioral Assessment Scale supplemental item
      measuring the persistence necessary on the part of the examiner to get the infant
      to attend to stimuli presented. The infants who were classified by parents as
      irritable at 1 month of age were more active and more attentive to stimuli in the
      first few days of life. CONCLUSIONS: Of interest was that the newborn nursery
      nurses cry ratings were not related to the later development of colic in these
      infants. Active infants who are sensitive to stimuli may be predisposed to infant
      irritability; however, further work is needed to understand the relationships of
      these infant characteristics to the human interactions and physical environments
      they encounter

PMID- 9773364
TI  - Risk of adverse outcomes in pregnant women exposed to solvents.
AB  - OBJECTIVE: To compare maternal and live birth outcomes of women who received
      consultation services between 1990 and 1993 from the Wisconsin occupational
      reproductive health nurse consultant (76% of whom were solvent-exposed) and a
      sample of women and their offspring selected randomly from birth certificate
      records drawn from the same years. DESIGN: Historical cohort study. SETTING:
      Consultations occurred primarily through telephone contacts with pregnant women
      workers in Wisconsin. Birth certificate records were used to obtain additional
      information. PARTICIPANTS: The convenience sample of largely solvent-exposed
      clients was compared with a random sample of women identified through birth
      records. MAIN OUTCOME MEASURES: Relative risk (RR) estimates. RESULTS:
      Confounding by race, prenatal care, and gestational diabetes was controlled by
      stratification. Logistic regression was used to control for age differences.
      Clients had elevated RR estimates for pregnancy-induced hypertension (RR = 2.4)
      and hydramnios (RR = 5.2), and their offspring were more likely to have 5-minute
      Apgar scores less than 8 (RR = 3.6). All other outcomes that were examined,
      including prematurity, low birth weight, and birth defects, were similar between
      groups. CONCLUSIONS: Most maternal and live birth outcomes were similar between
      the clients who sought consultation and the random sample of women. The current
      study supports previous research, which shows an elevated risk of pregnancy
      induced hypertension associated with solvent exposure in women. The increased
      risk of hydramnios found in this largely solvent-exposed cohort was not found in
      the literature.

PMID- 9773365
TI  - Transition time to full nipple feeding for premature infants with a history of
      lung disease.
AB  - OBJECTIVE: To (a) explore the contribution of infant, environmental, and
      historical factors to the number of days from initiation to achievement of full
      nipple feeding (transition time) for premature infants with a history of lung
      disease; (b) examine differences in the contribution of infant and environmental
      factors to transition time made by historical era, either earlier (in the 1980s)
      or later (in the 1990s); and (c) compare, within eras, the contribution to
      transition time of infant and environmental factors for infants with each lung
      diagnosis, respiratory distress syndrome (RDS) without bronchopulmonary dysplasia
      (BPD) or BPD. DESIGN: Data were collected at two midwestern hospitals from the
      records of premature infants with a diagnosis of either RDS without BPD or BPD.
      The influence on transition time of infant, environmental and historical factors
      was assessed with the Cox proportional hazards model. This analytic model, a form
      of regression analysis, also was used to explore how era influenced the
      contribution to transition time of infant and environmental factors. Finally, the
      contribution to transition time of infant and environmental factors was examined
      within diagnostic group for each era. SAMPLE: The hospital records audited were
      for infants who were 32 weeks gestational age or less with weight appropriate for
      gestational age. The number in each diagnostic group for each era was (a) BPD-
      Early, n = 35; (b) RDS--Early, n = 21; (c) BPD--Late, n = 21; and (d) RDS--Late,
      n = 15). RESULTS: All three types of factors (infant, environmental, and
      historical) contributed significantly (p < .05) to shortening or lengthening
      transition time. A diagnosis of BPD lengthened transition time only in the early
      era. Across both eras, the number of days on tube feedings significantly
      lengthened transition time, and the older the infant in postconceptional age
      (PCA) at initiation of nipple feeding, the shorter the transition time.
      CONCLUSION: The contribution of infant, environmental, and historical factors to
      transition time confirmed the basic structure of the theoretical model of
      transition time for premature infants with a history of lung disease. The
      influence of era on the contributions to transition time of infant and
      environmental factors suggests that care policy and practice have shortened the
      transition time. Although the current findings support the basic structure of the
      theoretical model for infants with either RDS or BPD, the marginally significant
      (p < .10) shortening effect of PCA on transition time for infants with BPD in
      both eras suggests that advancement to full nipple feeding may be limited by
      neurodevelopmental capacities, including respiratory control. How these
      capacities can be supported for advancement to full nipple feeding is a challenge
      for nursing practice and research.

PMID- 9773366
TI  - A study of miscarriage: development and validation of the Perinatal Grief
      Intensity Scale.
AB  - OBJECTIVE: This article outlines the development of the Perinatal Grief Intensity
      Scale (PGIS). It is based on a theoretical model developed to predict intensity
      of grief response to early pregnancy loss. DESIGN: Participants completed the
      PGIS by mail and made an overall assessment of their grief intensity by
      completing a single Likert-type item. PARTICIPANTS: A convenience sample of 186
      women who had experienced a miscarriage before 16 weeks gestation in the previous
      12-18 months. RESULTS: Fourteen items were retained after factor analyses,
      loading at .4 or greater. The 14 items loaded on a three-factor solution as
      predicted and accounted for 65% of the variance. Three factors were found to
      influence intensity of grieving: Reality of the pregnancy and baby within
      (Reality), congruence between the actual miscarriage experience and the woman's
      standard of the desirable (Congruence), and the ability of parents to make
      decisions or act in ways to increase this congruence (Confront Others).
      Chronbach's alpha for the entire instrument was .82, with subscale reliability
      scores of .89 (Reality), .84 (Confront Others), and .71 (Congruence). CONCLUSION:
      The PGIS demonstrates acceptable beginning reliability and validity in predicting
      grief intensity. Further testing of the instrument is needed with all types of
      pregnancy losses. The level of score needed to predict intense responses also
      needs to be determined.

PMID- 9773367
TI  - Alternative health care: an overview.
AB  - One-third of the patients seen in health care settings in a year also use
      alternative therapies. This article outlines ways to evaluate alternative
      therapies, including general resources that may be used for future reference, and
      discusses implications for practice and policy. Integrating alternative therapies
      into practice at several levels, from assessment to research, is examined, as are
      guidelines for helping patients chose alternative therapies.

PMID- 9773368
TI  - Yoga: intuition, preventive medicine, and treatment.
AB  - Mind-body fitness programs use a combination of muscular activity and mindful
      focus on awareness of the self, breath, and energy to promote health. The ancient
      discipline of yoga includes physical postures and breathing and meditation
      techniques. Scientific evidence exists about the physiologic effects of yoga.
      Mind-body fitness programs may offer therapeutic effects different from those
      offered by traditional body fitness programs.

PMID- 9773369
TI  - Bedside musical care: applications in pregnancy, childbirth, and neonatal care.
AB  - Although music therapy in health care settings is not new, bringing live music to
      the bedside is a new way of extending the caring tradition of nursing practice.
      Bedside musical care is consistent with a philosophy of holistic nursing practice
      and can be used during pregnancy, childbirth, and in neonatal care. It is defined
      as live music at the bedside, which is part of a treatment plan to foster
      integrity, well-being, and health for varied populations across the life span.

PMID- 9773371
TI  - The application of individualised fetal growth curves.
AB  - Individually adjusted or 'customised' growth charts aim to optimise the
      assessment of fetal growth by taking individual variation into account, and by
      projecting an optimal curve which delineates the potential weight gain in each
      pregnancy. This results in an increased detection rate of true growth restriction
      and a reduction in false positive diagnoses for IUGR. An adjustable standard can
      apply across geographical boundaries, as individual variation exceeds that
      between different maternity populations.

PMID- 9773370
TI  - Energy healing with women and children.
AB  - Western allopathic medicine has focused on illness care of the body. Energy
      healing is a complementary therapy focused on the mind-body-spirit connection and
      is especially useful for conditions for which allopathic medicine has few
      answers. Common in Eastern cultures, energy healing has developed as therapeutic
      touch and healing touch in Western nursing practice. An explanation of the
      scientific/theoretical basis of energy healing and case study presentations
      provide the framework for considering the application of this therapy to the care
      of women and children.

PMID- 9773372
TI  - Coronary blood flow in fetuses with intrauterine growth restriction.
AB  - The coronary circulation is the major determinant of myocardial oxygen balance
      which in turn is necessary for adequate cardiac function under a variety of
      conditions. Experiments in the fetal lamb suggest short-term functional coronary
      autoregulation in response to increase in afterload and acute hypoxemia. Long
      term, acute-on-chronic hypoxemia is associated with a marked increase of maximal
      myocardial flow reserve suggesting coronary vascular angio-neogenesis during the
      period of chronic hypoxemia. In the human fetus, flow velocity waveforms from the
      coronary arteries may be obtained by color-coded and pulsed wave Doppler
      sonography in normally developed fetuses from 31 weeks of gestation onwards under
      favorable imaging conditions. Coronary blood flow may also be visualized in
      selected fetuses with intrauterine growth restriction, absent or reversed end
      diastolic flow in the umbilical artery, cephalization of blood flow and abnormal
      flow patterns in the precordial veins and the umbilical vein. In these fetuses
      visualization of coronary blood flow may be possible as early as 26 weeks
      gestation and is consistently associated with a significant increase in the peak
      velocity index for veins in the ductus venosus. In this circulatory state,
      visualization of coronary blood flow is suddenly very easy. This "visualization
      threshold" may be a sign of maximal increase in coronary blood flow in an attempt
      to "spare" the fetal heart of hypoxemia. Although highly operator dependent,
      demonstration of coronary blood flow in intrauterine growth restriction
      identifies fetuses at high risk for intrauterine fetal death and postpartum
      circulatory failure.

PMID- 9773374
TI  - First trimester utero-placental circulation: maternal-fetal interaction.
AB  - Progressive development of embryonal and maternal circulations is essential for
      normal pregnancy outcome. The early embryo and trophoblast are very sensitive to
      the conditions under which they grow and differentiate. The most crucial event in
      human ontogeny is trophoblast invasion, a process that will enable chorionic and
      maternal circulations to develop in a synchronized fashion, balancing the
      metabolic needs with the capability to defend against oxidative stress.
      Trophoblast invasion transforms the spiral arteries into low resistance vessels,
      a change necessary for establishment of continuous forward blood flow once the
      villi are anchored and have obtained defense mechanisms against oxidative insult.
      Based on a review of current knowledge of human trophoblast and embryonic growth
      and development of embryonic and maternal placental circulations it seems that
      human ontogeny occurs in a low oxygen environment during the initial stages of
      pregnancy. This is similar to the environment in which the first single cell
      organisms appeared and it remains to be seen if the development process of the
      primitive single cell organisms, and its energy generating processes, is an
      appropriate model for studying early human ontogeny.

PMID- 9773373
TI  - Venous return and right ventricular diastolic function in ARED flow fetuses.
AB  - The absence or reversal of end-diastolic flow in the umbilical artery (UA) is
      widely accepted as an ominous sign of fetal compromise. However, in these high
      risk pregnancies, the significance of sequentially appearing changes of the
      venous return is poorly established. Doppler blood flow waveforms were
      longitudinally assessed in the inferior vena cava (IVC), ductus venosus (DV),
      umbilical vein (UV) and tricuspid valve, along with the UA, middle cerebral
      artery and descending aorta. Thirty-two serial Doppler studies were performed in
      six fetuses with intrauterine growth-retardation (IUGR). In the cases of absent
      or reversed UA endodiastolic flow, changes in the venous return were found
      following the same sequence: presence of dicrote pulsations in the UV, increase
      of retrograde flow in the IVC and reduction or inversion of DV velocity during
      atrial contraction. Transtricuspid flow patterns changed from normal to a
      restrictive pattern of ventricular filling. There were two intrauterine deaths
      and one early neonatal death. Our preliminary results suggest that the evaluation
      of the venous compartment of hemodynamically disturbed preterms fetuses along
      with right ventricular filling appears to be a useful model for investigating the
      physiopathology of fetal deterioration and, therefore, may yield indirect
      discriminatory signs of severe compromise.

PMID- 9773375
TI  - Current knowledge about fetal blood cells in the maternal circulation.
AB  - The aim of this review is to summarize the current status and future prospects of
      noninvasive prenatal genetic analysis by the isolation of fetal cells from the
      maternal circulation. The presence of fetal cells in maternal blood is no longer
      considered controversial. A variety of cell separation methods recover fetal
      cells from maternal blood; these differ in cost-effectiveness and required
      expertise. Fetal cell types that are useful for prenatal diagnosis are terminally
      differentiated and are unlikely to persist post-partum. Most investigators are
      isolating trophoblast sprouts, nucleated erythrocytes, or both from maternal
      blood. Advances in the understanding of cell surface and cytoplasmic protein
      expression have translated into better and more specific fetal cell
      identification. Fetal cells, once identified, are being screened for the presence
      of aneuploidy using chromosome-specific probes on interphase nuclei. Significant
      progress in single gene and single cell analysis has expanded the diagnostic
      possibilities for noninvasive fetal testing. Although fetal cells are generally
      rare in maternal blood samples, they appear to be more common when the fetus has
      trisomy 21. This is beneficial for clinical diagnosis. Furthermore, a large
      fetomaternal transfusion occurs at the time of labor and delivery in all pregnant
      women. This may establish fetal cell microchimerism in the mother, which may be
      implicated in the subsequent development of diseases such as scleroderma that are
      more common in women. The study of fetal cells in maternal blood, while
      technically challenging, provides a unique opportunity to explore the
      immunobiology of pregnancy.

PMID- 9773376
TI  - Intestinal flora in breast- and bottle-fed infants.
AB  - We verified whether an adapted formula, which presents poly-oligosaccharides
      containing maltose, promotes intestinal implantation of bacterial microflora to
      the extent that breast milk does, as an epidemiological link exists between
      newborn feeding methods and infant health. Stool specimens were taken and
      cultured at the fourth day of life from vaginally born neonates. Twenty-two were
      breast-fed and 20 were fed with formula. In breast-fed infants, the
      Bifidobacterium was significantly prevalent expressed in percentage (47.6% vs
      15%) and in mean bacterial fecal counts/g (7.1 +/- 0.8 vs 5.3 +/- 0.6).
      Enterococci prevailed in formula-fed infants (mean counts 6.7 +/- 0.9 vs 7.4 +/-
      0.5). Of interest is the significant and simultaneous presence of Bifidobacteria
      and Bacteroides in breast-fed infants. Our study indicates that flora with a diet
      dependent pattern is present from the fourth day of life. These results support a
      preference for breast feeding over formula feeding, even though renewed.

PMID- 9773377
TI  - Increased risk for abnormal placentation in women affected by myotonic dystrophy.
AB  - The obstetric histories of 26 women with myotonic dystrophy, who had a total of
      66 life births, were reviewed by means of questionnaires and medical reports. Six
      patients (23%) each had one pregnancy complicated by placenta praevia (affecting
      9% of all completed pregnancies), pointing toward a susceptibility to abnormal
      placentation in this disorder. As involvement of the genitourinary tract is
      common in myotonic dystrophy, an increased risk for placenta praevia has to be
      considered in the antenatal care of these patients.

PMID- 9773378
TI  - Gastro-intestinal complications following neonatal cardiac catheterisation.
AB  - BACKGROUND: Infants with congenital cyanotic heart disease are at increased risk
      of developing necrotising enterocolitis (NEC). We examined a cohort of infants
      with congenital cyanotic heart disease in order to assess the role of cardiac
      catheterisation in the pathogenesis of NEC. METHODS: Sixty-five infants with
      congenital cyanotic heart disease were assessed in a retrospective study. The
      incidence of gastrointestinal complications was compared between infants who
      required cardiac catheterisation and those who did not. RESULTS: There were 38
      infants who required cardiac catheterisation and 27 who did not. Both groups were
      similar for known risk factors for NEC. Eleven of the catheterised infants
      developed bloody stools versus 4 of the non-catheterised infants (OR 2.34; 95% CI
      0.65-8.36). Five of the catheterised infants developed classical NEC versus none
      of the non-catheterised infants (OR 4.24; 95% CI 0.47-38.5). Four of the five
      infants who developed NEC did so during re-introduction of feeds following
      cardiac catheterisation. CONCLUSION: Infants with congenital cyanotic heart
      disease appear to be at a greater risk of gastrointestinal complications
      including necrotising enterocolitis in the days following cardiac
      catheterisation. We suggest a more cautious approach to feeding is required
      during this period.

PMID- 9773379
TI  - Oscillatory ventilation for infants with respiratory distress syndrome--survey of
      current practice in the UK.
AB  - A questionnaire survey identified 55 neonatal units in the UK currently providing
      high frequency oscil latory ventilation (HFOV) for respiratory distress syndrome
      (RDS). Criteria used to select infants for both rescue and elective HFOV were
      found to vary widely between units. Personal clinical experience was the most
      common factor determining these criteria.

PMID- 9773380
TI  - The effects of Betamethasone on white blood cells during pregnancy with PPROM.
AB  - OBJECTIVE: To determine the effects of Betamethasone injections on maternal white
      blood cell counts. STUDY DESIGN: Thirteen pregnant women without fever or
      clinical infection and with premature rupture of the membranes at less than 34
      weeks gestation were studied. No subject had labor during the week of study.
      Daily complete blood counts were done before and on days one and two after two 12
      mg intramuscular injections of Betamethasone given 24 hours apart. RESULTS: The
      steroid injections produced a significant increase in total white counts from 9.8
      +/- 5.0 to 14.2 +/- 0.7 x 10(3) cells/cc. There was a significant increase in
      polymorphonucleocytes and a decrease in lymphocytes and monocytes. CONCLUSION:
      The use of Betamethasone injections to mature fetal lungs results in a
      leukocytosis, but total white cell counts remain less than 20 x 10(3) cells/cc.

PMID- 9773381
TI  - Absence of phospholipase A2 activity in genital Mycoplasma hominis.
AB  - The clinical relevance of vaginal colonization with Mycoplasma hominis (M
      hominis) as a cause of prematurity is doubtful. One of the possible pathways
      which could explain the role of M hominis in the induction of preterm labour is
      an increased synthesis of prostaglandins by a phospholipase A2 activity. The aim
      of this study was to prove whether M hominis secrets proteins with a PLA2
      activity and to test whether there are strain differences in the enzyme activity
      between M hominis isolated from women with normal pregnancy and those with
      preterm labour. Using specific radio-immunoassay we could not measure any PLA2
      activity in the supernatant of all investigated M hominis strains. We exclude the
      mechanism of induction of preterm labour by M hominis via an increased
      prostaglandin synthesis. Our findings make a relation between vaginal
      colonization with M hominis and prematurity unlikely.

PMID- 9773382
TI  - G-CSF, GM-CSF and IL-6 levels in cord blood: diminished increase of G-CSF and IL
      6 in preterms with perinatal infection compared to term neonates.
AB  - AIM: The objectives of this study were 1) to clarify the physiologic regulation
      of cytokines such as IL-6, G-CSF and GM-CSF in preterm and term neonates and 2)
      to evaluate the influence of perinatal stress and infection on endogenous
      cytokine levels. METHOD: We examined cord blood levels of G-CSF, GM-CSF and IL-6
      using a bioassay in 43 term and 44 preterm neonates. RESULTS: Compared to normal
      neonates (G-CSF: mean (m) = 97.6 +/- 16.3 pg/ml; IL-6: m = 20.2 +/- 4.6 pg/ml),
      we found elevated G-CSF levels in newborns with perinatal stress (m = 247.1 +/-
      72.1 pg/ml; p = 0.003) and increased levels for G-CSF (m = 8980.9 +/- 4388 pg/ml;
      p = 0.0003) and IL-6 (m = 705 +/- 322.3 pg/ml; p = 0.025) in neonates with
      infection. Term newborns with infection had higher G-CSF levels than preterms (m
      = 15575 +/- 9374 pg/ml versus m = 5384.1 +/- 4470.9 pg/ml; p = 0.024). G-CSF
      levels of newborns with infection were correlated with birth weight (r = 0.50; p
      = 0.024) but not with gestational age (r = 0.40; p = 0.057). GM-CSF was only
      detectable in cord blood in 4 cases of normal healthy neonates. CONCLUSIONS: The
      response of G-CSF levels in preterms to infection is diminished. Body cell mass
      is more important than gestational age to provide high G-CSF levels during states
      of infection.

PMID- 9773383
TI  - Endotracheal inhalatory sodium nitroprusside in severely hypoxic newborns.
AB  - This study examined the response of 10 newborns admitted to the Neonatal
      Intensive Care Unit of Hospital Universitario, UFMS, Campo Grande, MS, Brazil,
      submitted to mechanical ventilation under the following ventilator parameters:
      FiO2 = 100%, PIP (24 mmHg, rate > 30 mpm. All had severe hypoxia and were treated
      with a solution of sodium nitroprusside (SNP) administered through a special
      adapter for continuous endotracheal inhalation. Significant increases in PaO2,
      SaO2 and in PaO2/FiO2 ratio were observed at 1 h and at 6-8 h of treatment,
      whereas blood pressure did not change significantly while treatment was being
      delivered. No side effects such as methemoglobinemia or cyanogen accumulation
      were observed. Although appropriate studies using animal models have still to be
      conducted, present results suggest that endotracheal inhalation of SNP could
      constitute a valid form of treatment for newborns with persistent pulmonary
      hypertension or severe hypoxia of difficult management.

PMID- 9773385
TI  - Severe pulmonary hypertension in a neonate caused by premature closure of the
      ductus arteriosus following maternal treatment with diclofenac: a case report.
AB  - The administration of non-steroidal antiinflammatory drugs (NSAID) has
      occasionally been related to fetal and neonatal cardiopulmonary,
      gastrointestinal, cerebral and renal complications. This report describes a term
      newborn with severe persistent pulmonary hypertension due to premature closure of
      the ductus arteriosus following a 5 day maternal treatment with diclofenac two
      weeks before delivery. Pulmonary hypertension only responded to unusually high
      doses of inhaled NO. The treatment was necessary for 22 days suggesting
      structural alteration of pulmonary vasculature. The child recovered, but
      tricuspid regurgitation persisted, presumably because of irreversible ischemic
      damage of one papillary muscle. This is the first reported case of persistent
      pulmonary hypertension of the newborn (PPHN) in association with maternal
      diclofenac treatment and represents a most severe form of PPHN induced by NSAID.

PMID- 9773384
TI  - Fetal cerebral AV-malformation and cardiomegaly, diagnostic and therapeutic
      problems.
AB  - Intracerebral aneurysms are rare. However they are potentially life-threatening.
      Today by means of ultrasound investigations these malformations can occasionally
      be identified prenatally. In these cases questions of intrauterine therapy, mode
      and time of delivery and postnatal treatment have to be discussed with the
      parents. We describe two cases with prenatal diagnosis of intracerebral
      arteriovenous malformations, diagnostic workup, therapeutic options and fetal
      outcome.

PMID- 9773386
TI  - Intrauterine growth acceleration in the case of a severe form of
      mucopolysaccharidosis type VII.
AB  - We describe a Japanese male infant with mucopoly-saccharidosis type VII (MPS VII)
      who was born at 32 weeks of gestation presenting as a non-immune hydrops fetalis.
      His birth weight was 2900 g (+4.1 SD), his birth length was 48 cm (+2.2 SD), and
      thoracic spine length was 9.5 cm (+2.7 SD) at birth. Ossification center was
      already discernible bilaterally in coracoid process and distal femur at birth. In
      eight newborn infants with fetal hydrops of various other etiologies born in our
      institution, birth length ranged from -0.2 to -1.5 SD and thoracic spine length
      ranged from +0.5 to -1.7 SD, and neither ossification center of coracoid process
      nor distal femur were visible. The above data indicate that hydrops fetalis form
      of MPS VII is associated with intrauterine growth acceleration accompanied by
      early bone maturation. This feature may be useful in differentiating MPS VII
      associated hydrops fetalis from those of other etiologies.

PMID- 9773388
TI  - Intrauterine fetal volvulus presenting as fetal distress on cardiotocographic
      monitoring: a case report.
AB  - A rare case of intrauterine fetal midgut volvulus is described. The condition was
      diagnosed post delivery after the patient presented with markedly decreased fetal
      movements and fetal distress on cardiotocographic monitoring at 35 weeks'
      gestation. This baby was delivered and resuscitated before proceeding to
      laparotomy and bowel resection. The infant has subsequently made a good recovery.
      Intrauterine volvulus is rare, and presentation in this case was with fetal
      distress which has not previously been described as a presenting feature.

PMID- 9773389
TI  - Two cases of primary pulmonary hypertension diagnosed during pregnancy.
AB  - Primary pulmonary hypertension (PPH) is a rare clinical entity with a high
      mortality in pregnancy, delivery and postpartum. This paper describes two
      clinical cases of PPH diagnosed in pregnancy with different severity and
      outcomes; Case 1 was diagnosed as PPH at 34 weeks of gestation with pulmonary
      arterial pressure of 60 mmHg and delivered successfully by cesarean section with
      uneventful postoperative course. Case 2 was diagnosed as PPH at 26 weeks of
      gestation with pulmonary arterial pressure of 120 mmHg and delivered by cesarean
      section but died on the 7th day after the operation because of serious and
      progressive pulmonary hypertension. Patients with primary pulmonary hypertension
      should avoid pregnancy because of the high mortality, although some cases
      including ours have been reported with positive outcome.

PMID- 9773387
TI  - Pregnancy and lactation in homozygous beta-thalassemia major.
AB  - Successful pregnancies in patients with transfusion-dependent homozygous beta
      thalassemia major are rare. We report the course of a pregnancy and newborn data
      during lactation and desferrioxamine therapy in the mother. The twin-pregnancy
      was complicated by preeclampsia. Besides normal iron level in breast milk, no
      clinical or hematological abnormalities due to desferrioxamine therapy could be
      shown in the newborns. Our observation suggests that chelating therapy during
      lactation does not alter iron excretion in breast milk or iron metabolism in
      offsprings. Breast feeding in newborns from patients with thalassemia major and
      desferrioxamine therapy seems justified.

PMID- 9773390
TI  - In vivo evaluation of the absorption and gastrointestinal transit of avitriptan
      in fed and fasted subjects using gamma scintigraphy.
AB  - The study was conducted to assess the bioavailability of avitriptan after a
      standard high fat meal, in relation to gastrointestinal transit. Six healthy male
      subjects were enrolled in a four-period study with a partial replicate design
      where each was administered 150-mg avitriptan capsule (i) after an overnight
      fast, (ii) 5 min after a standard high-fat breakfast, and (iii) 4 hr after a
      standard high fat breakfast. The treatment administered in Period 3 was repeated
      in Period 4 to assess intrasubject variations in pharmacokinetics and
      gastrointestinal (GI) transit. Avitriptan capsules were specially formulated with
      nonradioactive samarium chloride hexahydrate which was neutron-activated to gamma
      emitting samarium before dosing. Serial blood samples were collected for analysis
      of avitriptan up to 24-hr postdose, and serial scintigraphic images were obtained
      to assess the plasma concentration-time profile in relation to the GI transit of
      the avitriptan capsule contents. Bioavailability of avitriptan was reduced when
      administered in the fed condition but only the decrease in AUC(INF) was
      statistically significant. Tmax was significantly delayed between the fed
      conditions and the fasted condition. Qualitative appearance of plasma
      concentration-time profiles for avitriptan could be related to the manner in
      which the drug emptied from the stomach. It was also apparent that avitriptan
      exerted a secondary pharmacologic effect that temporarily suspended gastric
      emptying in the fasted treatment. Thus, when gastric emptying was interrupted and
      then resumed, the net result was a double peak in some of the individual plasma
      concentration profiles. Scintigraphic analysis also demonstrated that upon
      emptying from the stomach, avitriptan was rapidly absorbed from the upper small
      intestine. In the fed state, gastric emptying was slow and continuous resulting
      in extended absorption and a lower occurrence of double peaks. Qualitatively, the
      intrasubject variability in Cmax and AUC could be explained by the intrasubject
      variability in gastric emptying in both fasted and fed conditions.

PMID- 9773391
TI  - Lumping of whole-body physiologically based pharmacokinetic models.
AB  - Lumping is a common pragmatic approach aimed at the reduction of whole-body
      physiologically based pharmacokinetic (PBPK) model dimensionality and complexity.
      Incorrect lumping is equivalent to model misspecification with all the negative
      consequences to the subsequent model implementation. Proper lumping should
      guarantee that no useful information about the kinetics of the underlying
      processes is lost. To enforce this guarantee, formal standard lumping procedures
      and techniques need to be defined and implemented. This study examines the
      lumping process from a system theory point of view, which provides a formal basis
      for the derivation of principles and standard procedures of lumping. The lumping
      principle in PBPK modeling is defined as follows: Only tissues with identical
      model specification, and occupying identical positions in the system structure
      should be lumped together at each lumping iteration. In order to lump together
      parallel tissues, they should have similar or close time constants. In order to
      lump together serial tissues, they should equilibrate very rapidly with one
      another. The lumping procedure should include the following stages: (i) tissue
      specification conversion (when tissues with different model specifications are to
      be lumped together); (ii) classification of the tissues into classes with
      significantly different kinetics, according to the basic principle of lumping
      above; (iii) calculation of the parameters of the lumped compartments; (iv)
      simulation of the lumped system; (v) lumping of the experimental data; and (vi)
      verification of the lumped model. The use of the lumping principles and
      procedures to be adopted is illustrated with an example of a commonly implemented
      whole-body physiologically based pharmacokinetic model structure to characterize
      the pharmacokinetics of a homologous series of barbiturates in the rat.

PMID- 9773392
TI  - The pharmacokinetics of saquinavir: a Markov chain Monte Carlo population
      analysis.
AB  - Saquinavir is an HIV proteinase inhibitor marketed as a treatment for HIV
      infection. The drug has potent (Ki approximately 0.1 nM) antiviral activity and
      acts by inhibiting the processing of gag and gag-pol polyproteins, thus blocking
      the maturation of replicated viral particles. By assuming standard two
      compartment disposition kinetics in combination with a variety of absorption
      processes we have identified two structural models that perform well with respect
      to describing the pharmacokinetic behavior of saquinavir when administered to
      healthy human volunteers from various Phase I studies. These structural models
      have been implemented for population analysis of these Phase I data via the
      Bayesian Markov chain Monte Carlo approach. We conclude that saquinavir exhibits
      complex and highly variable behavior, but can be modeled adequately using a two
      compartment zero-order absorption model. There is also an indication that
      saquinavir kinetics may be time-dependent.

PMID- 9773393
TI  - Single-dose pharmacokinetics of rifapentine in women.
AB  - Gender can be an important variable in the absorption and disposition of some
      drugs. In this open-label study, 15 healthy, nonsmoking women received a single
      600-mg oral dose of rifapentine. Plasma samples were obtained at frequent
      intervals for up to 72 hr after the dose to determine the pharmacokinetic (PK)
      parameters of rifapentine and its active metabolite, 25-desacetyl-rifapentine.
      Peak plasma rifapentine concentrations (Cmax) were observed 5.9 hr after
      ingestion of the single dose. The mean area under the rifapentine plasma
      concentration-time curve [AUC(0-->infinity)] was 325 micrograms.hr ml and the
      mean elimination half-life (t1/2) was 16.3 hr. Plasma concentrations for the 25
      desacetyl metabolite peaked at 15.4 hr after the rifapentine dose and declined
      with a terminal half-life of 17.3 hr. These rifapentine and 25-desacetyl
      rifapentine PK data in women were compared to data generated previously in
      healthy men. Striking similarities in the PK profiles of parent drug and
      metabolite were found in the two populations. Mean differences in rifapentine
      CL/F (12%) and t1/2 (2%) were small. The only adverse event reported in the
      female subjects was discoloration of the urine. Based on these PK and safety
      data, no dosage adjustments for rifapentine based on gender are recommended.

PMID- 9773394
TI  - Estimation of confidence intervals for area under the curve from destructively
      obtained pharmacokinetic data.
AB  - The area under the curve (AUC) of the concentration-time curve for a drug or
      metabolite, and the variation associated with the AUC, are primary results of
      most pharmacokinetic (PK) studies. In nonclinical PK studies, it is often the
      case that experimental units contribute data for only a single time point. In
      such cases, it is straightforward to apply noncompartmental methods to determine
      an estimate of the AUC. In this report, we investigate noncompartmental
      estimation of the AUC using the long-trapezoidal rule during the elimination
      phase of the concentration-time profile, and we account for the underlying
      distribution of data at each sampling time. For data that follow a normal
      distribution, the log-trapezoidal rule is applied to arithmetic means at each
      time point of the elimination phase of the concentration-time profile. For data
      that follow a lognormal distribution, as is common with PK data, the log
      trapezoidal rule is applied to geometric means at each time point during
      elimination. Since the log-trapezoidal rule incorporates nonlinear combinations
      of mean concentrations at each sampling time, obtaining an estimate of the
      corresponding variation about the AUC is not straightforward. Estimation of this
      variance is further complicated by the occurrence of lognormal data. First-order
      approximations to the variance of AUC estimates are derived under the assumptions
      of normality, and lognormality, of concentrations at each sampling time. AUC
      estimates and variance approximations are utilized to form confidence intervals.
      Accuracies of confidence intervals are tested using simulation studies.

PMID- 9773395
TI  - A use of Monte Carlo integration for population pharmacokinetics with
      multivariate population distribution.
AB  - This paper describes a use of Monte Carlo integration for population
      pharmacokinetics with multivariate population distribution. In the proposed
      approach, a multivariate lognormal distribution is assumed for a population
      distribution of pharmacokinetic (PK) parameters. The maximum likelihood method is
      employed to estimate the population means, variances, and correlation
      coefficients of the multivariate lognormal distribution. Instead of a first-order
      Taylor series approximation to a nonlinear PK model, the proposed approach
      employs a Monte Carlo integration for the multiple integral in maximizing the log
      likelihood function. Observations below the lower limit of detection, which are
      usually included in Phase 1 PK data, are also incorporated into the analysis.
      Applications are given to a simulated data set and an actual Phase 1 trial to
      show how the proposed approach works in practice.

PMID- 9773396
TI  - On continuity of integration methods for AUC. A note.
AB  - A lack of monotonicity and discontinuity of some integration methods for AUC, as
      a function of measured concentration, is demonstrated. Hybrid methods consisting
      of either parabolas-through-the-origin or the alpha-function method followed by
      the log-trapezoidal method were found to be discontinuous at the switching point.
      The stable piecewise third-order polynomial method appeared to be nonmonotonic as
      well as discontinuous.

PMID- 9773397
TI  - Academic medical centers: whence they came, where they went.

PMID- 9773398
TI  - Activation of endothelial cells in preeclampsia: increased neutrophil-endothelial
      adhesion correlates with up-regulation of adhesion molecule P-selectin in human
      umbilical vein endothelial cells isolated from preeclampsia.
AB  - OBJECTIVE: Increased endothelial activation has been suggested to be important in
      the pathophysiology for preeclampsia. Our objective was to examine whether in
      preeclampsia neutrophil adherence to endothelial cells is increased and whether
      endothelial cell-surface adhesion molecule expression is up-regulated. METHODS:
      Endothelial cells were isolated from normal (n = 10) and preeclamptic (n = 9)
      human umbilical veins (HUVECs). Neutrophils were isolated from normal, healthy,
      nonpregnant female volunteers. Freshly isolated neutrophils were labeled with
      51Cr, and labeled neutrophils were coincubated with confluent normal and
      preeclamptic endothelial monolayers. Adhesion assays were then performed. To
      determine whether in preeclampsia endothelial cellular-surface adhesion molecules
      are responsible for increased neutrophil-endothelial adhesion, cellular adhesion
      molecule expression of P-selectin, intercellular adhesion molecule-1 (ICAM-1),
      vascular cellular adhesion molecule-1 (VCAM-1), and E-selectin were examined by
      an enzyme-linked binding assay. Furthermore, adhesion assays were also performed
      on HUVECs pretreated with antibodies against P-selectin, ICAM-1, VCAM-1, and E
      selectin. RESULTS: Neutrophil adhesion to the HUVECs from preeclamptic
      pregnancies was significantly increased compared with neutrophil adhesion to the
      HUVECs from normal pregnancies (P < .01). Expression of cellular-surface adhesion
      molecule of P-selectin was significantly higher (P < .01) and ICAM-1 was
      significantly lower (P < .05) in HUVECs isolated from preeclampsia than from
      normal controls, whereas there was no difference for VCAM-1 and E-selectin
      expression between HUVECs from normal and preeclamptic pregnancies. No
      differences were found for neutrophil-endothelial adhesion on normal HUVECs
      pretreated with anti-P-selectin, anti-ICAM-1, anti-VCAM-1, and anti-E-selectin
      compared with the untreated cells. However, pretreatment of preeclampsia HUVECs
      with anti-P-selectin, anti-ICAM-1, anti-VCAM-1, and anti-E-selectin completely or
      partially blocked the neutrophil-endothelial adhesion compared to the untreated
      cells. CONCLUSION: There is a significant increase in neutrophil adhesion to
      HUVECs that are isolated from preeclamptic pregnancies compared with normal
      controls. This increase appears to be a result of up-regulation of the cell
      surface adhesion molecule P-selectin. Elevated P-selectin expression may play a
      significant role in neutrophil-endothelial hyperadhesiveness and contribute to
      vascular complications associated with preeclampsia.

PMID- 9773399
TI  - Low-density lipoprotein particle size decreases during normal pregnancy in
      association with triglyceride increases.
AB  - OBJECTIVE: To characterize the changes in low-density lipoprotein (LDL) peak
      particle diameter (diameter of the predominant LDL subclass) in relation to
      changes in serum triglyceride concentration during successive stages of normal
      gestation and postpartum. METHODS: Nonfasting venous blood was obtained
      longitudinally during and after uncomplicated primiparous pregnancy from 10
      nonsmoking women with no history of metabolic disorders. Plasma LDL diameter was
      determined by nondenaturing polyacrylamide gel electrophoresis. Serum
      concentrations of total cholesterol, triglyceride, apolipoprotein B,
      apolipoprotein A-I, and LDL-cholesterol were measured. Gestational changes were
      analyzed by one-way repeated-measures analysis of variance and the paired
      multiple comparison Student-Newman-Keuls test. Pearson coefficients were computed
      for correlation of serum lipids and LDL diameter. RESULTS: Low-density
      lipoprotein diameter decreased progressively with advancing gestation, evident by
      16-20 weeks relative to 5-12 weeks. Seven of 10 cases were subclass pattern B
      (diameter less than 255 A) by term, indicating that small, dense particles
      predominated. The average diameter decrease from early to late gestation was 13
      A. All subjects reverted to subclass pattern A (diameter 255 A or more) by 6-12
      weeks postpartum, indicating prevalence of large, buoyant LDL. Low-density
      lipoprotein diameter correlated inversely with concentrations of serum
      triglyceride (r = -.61, P < .0001), apo B (r = -.66, P < .0001), cholesterol (r =
      -.53, P < .001), LDL cholesterol (r = -.45, P < .005), and apo A-I (r = -.39, P <
      .02). CONCLUSION: Gestational triglyceride increases are accompanied by
      progressive decreases in LDL diameter in a majority of cases. These changes
      undergo reversal postpartum and therefore are transient. Small, dense LDL
      particles have a number of properties capable of altering vascular function.
      However, the consequences of the gestational LDL size decrease for maternal and
      fetal metabolism remain unknown.

PMID- 9773400
TI  - Comparison of the in vivo activity of different oxytocin antagonists in the
      pregnant baboon.
AB  - OBJECTIVE: To ascertain the relative activity of five oxytocin antagonists (OTAs)
      in vivo in a tethered pregnant baboon model and compare these results to
      previously reported affinities in human and rat oxytocin receptor assays and
      median effective dose in rat uterotonic bioassays. METHODS: Pregnant tethered
      baboons between days 130 and 160 of pregnancy were given an oxytocin challenge
      test 1 minute after infusion of 1 mg of one of five randomly selected OTAs: ANTAG
      I, ANTAG II, ANTAG III, L366948, and Atosiban. Once the uterine response to
      oxytocin returned to normal (1-8 days) the OCT was repeated with one of the
      remaining, untested OTAs during the 130-160 day period. Uterine activity, the
      time until the first significant response, and the dose of oxytocin needed to
      induce this response were all factored into one expression, the antagonist
      response interval (ARI). RESULTS: When expressed as ratio to ANTAG I the relative
      ARI for the OTAs were 0, .5, 1.0, 2.4 and 59.2 for L366948, Atosiban, ANTAG I,
      ANTAG II, and ANTAG III, respectively. ANTAG III and L366948 were significantly
      different from each other and the three other OTAs (P < .05). The log10 ARI for
      the 4 active OTAs when correlated with the log10 of the human and rat oxytocin
      receptor affinities and the rat uterotonic bioassay were all highly correlated (r
      = .99; P < .05). CONCLUSION: ANTAG III is a potent, long-acting OTA in vivo in
      the pregnant baboon and has the potential as a tocolytic in humans.

PMID- 9773401
TI  - Calibration of a reflectance pulse oximeter in fetal lambs for arterial oxygen
      saturations below 70%.
AB  - OBJECTIVE: To calibrate a reflectance pulse oximeter developed at the Division of
      Perinatal Physiology, University Hospital of Zurich, for monitoring of oxygen
      saturations below 70%. METHODS: Oxygen saturation measured noninvasively with the
      reflectance pulse oximeter in fetal sheep was compared with oxygen saturation of
      arterial blood samples measured by a conventional two-wavelength oximeter. Oxygen
      saturation was varied by stepwise reduction of the inspired oxygen concentration
      of the ewe. RESULTS: A total of 58 data pairs was obtained from five fetuses,
      with a range of 10.9-73.5% for the reference method and 6.8-69.2% for the pulse
      oximetry oxygen saturation values. There was good correlation between the results
      obtained by the two methods (r2 = .89, P < .0001), with a 95% confidence interval
      of +/- 12.5%. The pulse oximeter showed a precision of 6.2% oxygen saturation.
      CONCLUSION: The Zurich reflectance pulse oximeter offers valid measurements of
      oxygen saturation levels down to 10% oxygen saturation, and is therefore suitable
      for monitoring the fetus during delivery.

PMID- 9773402
TI  - Effects of estrogen on tight junctional resistance in cultured human umbilical
      vein endothelial cells.
AB  - OBJECTIVE: To study the effects of estrogen on transendothelial paracellular
      permeability in women. METHODS: Human umbilical vein endothelial cells (HUVEC)
      obtained from women were grown on filters. The paracellular permeability
      characteristics were determined in terms of changes in the permeability to the
      polar acid pyranine (Ppyr) and as changes in the transendothelial electrical
      resistance (RTE). Tight junctional resistance characteristics were assayed by
      lowering luminal NaCl and measuring the dilution potential, and were expressed as
      the ratio of monoion mobility uCl/uNa (cation selectivity). RESULTS: Low
      extracellular calcium and hyperosmolarity increased Ppyr and decreased RTE. The
      former but not the latter condition abolished the endothelium-specific cation
      selectivity. Treatment with 10 nM of estradiol-17 beta had no effect on RTE, but
      it increased the cation selectivity. The effect of estradiol required 1-6 hours'
      incubation with the hormone; it was dose dependent and saturable, with a median
      effective concentration of estradiol of 1 nM. Diethylstilbestrol, but not
      estriol, could mimic the effect of estradiol, and the estrogen receptor
      antagonist ICI-182, 780 blocked it. CONCLUSION: Cultured HUVEC cells form patent
      tight junctions. Estrogens increase the cation selectivity across HUVEC cultures.
      The effect of estrogen may be mediated by an estrogen receptor. These effects may
      be important for vasculoprotection in cases of sudden changes in ions levels
      across the capillary wall, such as ischemia or reperfusion.

PMID- 9773404
TI  - Expression of HOXD10 gene in normal endometrium and endometrial adenocarcinoma.
AB  - OBJECTIVE: Hox genes encode DNA transcription regulatory proteins that contain a
      conserved 61 amino acid protein called the homeodomain. Although best known for
      their role in cellular differentiation during embryonic development, aberrant
      expression of these genes has been associated with hematologic and solid
      neoplasms. The purpose of this study was to determine the relative expression of
      HOXD10 in human endometrial adenocarcinomas. METHODS: mRNA was isolated from 7
      normal endometrial specimens and 28 endometrial adenocarcinoma specimens. cDNA
      was synthesized using random hexamer primers. The expression of HOXD10 relative
      to beta-tubulin (internal control) was assessed by densitometric comparison of co
      amplified Phosphorus-32 (32P) labeled gene products separated by agarose gel
      electrophoresis. Direct sequencing of purified HOXD10 polymerase chain reaction
      product was also performed. RESULTS: The sequence of the purified HOXD10 product
      corresponds to the known DNA sequence reported in the National Institute of
      Health Gene Bank. mRNA expression of HOXD10 relative to beta-tubulin is
      significantly lower in endometrial carcinomas than in normal endometrium.
      Furthermore, the ratio of HOXD10 to beta-tubulin expression varies inversely with
      the histologic grade of the tumor (P = .0009). CONCLUSION: Cancer is a multistep
      process involving the aberrant expression of genes that regulate cell growth and
      differentiation. Human HOXD10 gene expression is altered in endometrial carcinoma
      and varies with the histologic grade of differentiation. This observation
      supports the theory that homeobox genes play a role in oncogenesis.

PMID- 9773403
TI  - Effect of progestin on the ovarian epithelium of macaques: cancer prevention
      through apoptosis?
AB  - OBJECTIVE: The apoptosis pathway is a vital mechanism in vivo that functions to
      eradicate genetically damaged cells prone to malignancy. The purpose of this
      study was to determine whether oral contraceptives, which confer significant
      protection against subsequent epithelial ovarian cancer, induce apoptosis in the
      ovarian epithelium. METHODS: Female cynomolgus macaques (N = 75) were randomized
      to receive a diet for 35 months containing either no hormones, the oral
      contraceptive Triphasil (Wyeth-Ayerst Laboratories, Philadelphia, PA), the
      estrogenic component of Triphasil (ethinyl estradiol) alone, or the progestin
      component of Triphasil (levonorgestrel) alone, each administered in a cyclic
      fashion. At study termination, the animals underwent ovariectomy and the ovarian
      epithelium was examined morphologically and immunohistochemically for apoptosis.
      The percentage of ovarian epithelial cells undergoing apoptosis was measured in
      each animal and compared between the treatment groups. RESULTS: The median
      percentage of ovarian epithelial cells undergoing apoptosis by treatment was
      control (3.8%), ethinyl estradiol (1.8%), Triphasil (14.5%), and levonorgestrel
      (24.9%). Compared with control and ethinyl estradiol-treated monkeys, a
      statistically significant increase in the proportion of apoptotic cells was noted
      in the ovarian epithelium of monkeys treated with the oral contraceptive
      Triphasil (P < or = .01) or levonorgestrel (P < .001), with a maximal effect (six
      fold) seen in the group treated with levonorgestrel alone. CONCLUSION: Oral
      contraceptive progestin induces apoptosis in the ovarian epithelium. Given the
      importance of the apoptosis pathway for cancer prevention, an effective
      chemopreventive strategy may be possible using progestins or other agents that
      selectively induce apoptosis in the ovarian epithelium to prevent the development
      of ovarian cancer.

PMID- 9773405
TI  - Aberrant splicing of the TSG101 tumor suppressor gene in human breast and ovarian
      cancers.
AB  - OBJECTIVE: To determine whether large deletions or other alterations in the
      putative tumor suppressor gene TSG101 play a role in the molecular pathogenesis
      of breast and ovarian cancers. METHODS: Expression of TSG101 transcripts was
      examined in breast and ovarian cancers using the reverse transcriptase-polymerase
      chain reaction (RT-PCR), and selected transcripts were sequenced. Southern blot
      analysis was performed to determine whether there were genomic deletions in the
      TSG101 gene, and Northern blot analysis was used to examine the relative
      abundance of various transcripts. RESULTS: All the cancerous and normal breast
      tissue examined expressed full length 1145 base pair (bp) TSG101 transcripts.
      Additional truncated transcripts were seen using the RT-PCR in 57 (64%) of 89
      primary breast cancers, 1 (20%) of 5 breast cancer cell lines, 3 (50%) of 6
      normal breast tissues, 16 (64%) of 25 primary ovarian cancers and 1 (33%) of 3
      ovarian cancer cell lines. Only the primary breast (21%) and ovarian (24%)
      cancers had three or more truncated transcripts. None of the normal tissues or
      cell lines examined had more than two aberrant transcripts. DNA sequencing
      revealed that the most commonly expressed truncated transcript arises because of
      loss of 902 bp between codons 153 and 1055. Only full length TSG101 transcripts
      were seen on Northern blot analysis of breast cancer cell lines, however. There
      was no evidence of genomic deletions in the TSG101 gene on Southern blot
      analysis. CONCLUSION: Truncated TSG101 transcripts that probably represent splice
      variants are present in some breast and ovarian cancers, but there is no evidence
      to suggest that loss of this putative tumor suppressor gene plays a role in the
      molecular pathogenesis of these cancers.

PMID- 9773406
TI  - The sepsis-coagulant axis: a review.
AB  - Activation of coagulation is a normal component of the acute inflammatory
      response. Inflammatory cytokines initiate coagulation events locally at sites of
      inflammation by converting endothelium from an antithrombotic surface to a
      prothrombotic surface; by stimulating tissue factor production, which activates
      both the extrinsic and intrinsic coagulation systems; and by stimulating
      production of platelet-activating factors. The fibrinolytic system is initially
      activated but is subsequently inhibited. This results in a marked imbalance in
      coagulation and fibrinolysis resulting in a net procoagulant state. When thrombin
      generation and platelet activation exceed the body's capacity to inactivate or
      remove these factors, disseminated intravascular coagulation (DIC) results. DIC
      directly contributes to multiple organ failure and death associated with sepsis.
      Presently available treatments (i.e., heparin and aspirin) are relatively
      ineffective in treating DIC; however, newer, more potent drugs may soon be
      available for clinical use.

PMID- 9773407
TI  - Evaluation of single-agent mitoxantrone as chemotherapy for relapsing canine
      lymphoma.
AB  - Many chemotherapeutic regimens will induce remission in dogs with lymphoma, but
      almost all dogs suffer relapse. Mitoxantrone was selected for evaluation as
      single-agent chemotherapy for relapsing canine lymphoma based on its use in
      humans undergoing salvage chemotherapy for non-Hodgkin's lymphoma and its
      tumoricidal effect against canine lymphoma. Dogs entered into study had
      multicentric lymphoma, and all had been treated solely with a standard
      combination chemotherapy protocol. At 1st relapse, all dogs were again staged and
      underwent lymph node biopsy. Mitoxantrone was administered IV at 6 mg/m2 every 21
      days. Dogs were evaluated for lymphadenopathy before each dose of mitoxantrone.
      Fifteen dogs were entered into study. The average age (+/- SEM) of the dogs
      studied was 7.7 +/- 0.91 years, and most dogs were large (mean +/- SEM weight,
      24.44 +/- 2.15 kg). Twelve dogs (80%) had B-cell lymphoma, and 3 had T-cell
      lymphoma. Dogs were staged IV (n = 12) or V (n = 3). The median duration of
      chemotherapy before entry into the study was 98 days. Overall median duration of
      response after mitoxantrone chemotherapy was 21 days. Complete responses were
      attained in 7 of 15 dogs (47%) with a median response duration of 84 days. Nine
      of 15 (60%) dogs attained a complete remission with additional chemotherapy after
      failing mitoxantrone chemotherapy. Mild toxicities were observed after
      mitoxantrone administration. No adverse reactions were observed during
      mitoxantrone infusions. The results of this study demonstrate that mitoxantrone,
      as a single agent, has limited value for dogs with lymphoma at 1st relapse after
      conventional multidrug chemotherapy.

PMID- 9773408
TI  - Laryngeal paralysis-polyneuropathy complex in young Rottweilers.
AB  - Five Rottweiler puppies from 3 unrelated litters developed inspiratory stridor at
      11-13 weeks of age. Physical examination disclosed tetraparesis in all dogs, and
      bilateral lenticular cataracts in 4 dogs. Laryngeal examination under light
      anesthesia showed laryngeal paralysis in all dogs. Electrodiagnostic testing
      revealed denervation potentials in the distal appendicular muscles of 4 dogs
      tested and in the intrinsic laryngeal muscles of 2 dogs tested. Motor nerve
      conduction velocity was slightly low in 1 dog. Neurogenic muscular atrophy was
      found in distal appendicular muscles (n = 3) and intrinsic laryngeal muscles (n =
      2), and degenerative changes were found in peripheral nerves (n = 3) and
      recurrent laryngeal nerves (n = 2). No abnormalities were detected in the spinal
      cord, spinal nerve roots, or ganglia of 3 dogs autopsied. The clinical,
      electrophysiologic, and histopathologic findings support a diagnosis of
      polyneuropathy and resemble the finding reported in young Dalmatians. Young dogs
      with laryngeal paralysis should be evaluated neurologically to rule out a more
      generalized polyneuropathy. The condition is suspected to be hereditary in nature
      and the prognosis is poor.

PMID- 9773409
TI  - Ultrasound-guided fine-needle aspiration of focal parenchymal lesions of the lung
      in dogs and cats.
AB  - Ultrasound-guided fine-needle aspiration (FNA) of the lung was performed on 16
      dogs and 3 cats with consolidated pulmonary lesions or masses identified on
      thoracic radiographs. The cytologic results from the FNA were confirmed by
      histopathology, response to treatment, or microscopic identification of
      Blastomyces organisms. Neoplasia was identified correctly by FNA cytology in 10
      of 11 animals, and no false positive results occurred, yielding a positive
      predictive value of 100%. Of 8 animals with infectious disease, 5 of 6 had
      blastomycosis and 1 had a bacterial infection, based on cytologic evaluation.
      Eight animals required sedation for the procedure, and none had clinical
      complications. We conclude that ultrasound-guided FNA of pulmonary mass lesions
      is an inexpensive, safe, and accurate method for diagnosing blastomycosis or
      neoplasia, especially carcinomas, in dogs and cats.

PMID- 9773410
TI  - Thyroid-stimulating hormone stimulation tests in cardiomyopathic Doberman
      pinschers: a retrospective study.
AB  - Thyroid-stimulating hormone (TSH) response tests were performed in 152 Doberman
      Pinschers. Seventy-nine dogs had cardiomyopathy (46 were in congestive heart
      failure [CHF] and 33 were not in CHF). Seventy-three dogs were presented for
      noncardiac problems (15 with skin disease, 21 with neurologic disease, 20 with
      internal medicine disorders, and 17 with other problems), although some may have
      had cardiomyopathy. The TSH response test results in the cardiomyopathic group
      were interpreted as normal or euthyroid-sick in 45 (57%) dogs, abnormal in 23
      (29%) dogs, and equivocal in 11 (14%) dogs. The prevalence of hypothyroidism in
      the CHF and non-CHF cardiomyopathy groups was not different. Among the dogs
      presented for noncardiac problems, 27 (37%) were assessed as normal or euthyroid
      sick, 29 (40%) as hypothyroid, and 17 (23%) as equivocal. No significant
      differences were found in the prevalence of hypothyroid test results among the
      subgroups of these dogs. The prevalence of hypothyroidism was not higher in the
      cardiomyopathic group compared to the other group, and 63 and 49% of
      cardiomyopathic dogs with or without CHF, respectively, tested as either
      euthyroid or euthyroid-sick.

PMID- 9773411
TI  - Feline lymphoma (145 cases): proliferation indices, cluster of differentiation 3
      immunoreactivity, and their association with prognosis in 90 cats.
AB  - Paraffin-embedded, formalin-fixed tissue samples from 145 cats with lymphoma were
      analyzed for cluster of differentiation 3 (CD3, a surface antigen)
      immunoreactivity, argyrophilic nucleolar organizer region (AgNOR) frequency, and
      proliferating cell nuclear antigen labeling index (PCNA-LI). This information
      along with signalment, anatomic site, and feline leukemia virus (FeLV) antigen
      status was used to determine the potential of these indicators to predict
      response to therapy, remission, and survival times, and to characterize cats with
      lymphoma in the era of general availability of FeLV testing and vaccination.
      Alimentary lymphoma, primarily occurring in older, FeLV-negative cats, was the
      most common site of involvement. Although the majority of tumors from FeLV
      positive cats were CD3-immunoreactive, only one half of CD3-immunoreactive tumors
      occurred in FeLV-positive cats. Median remission duration and survival times were
      126 days and 143 days, respectively, for all cats. Measures of tumor cell
      proliferation (AgNOR frequency and PCNA-LI) and CD3-immunoreactivity were not
      predictive of outcome. When all prognostic factors were accounted for by
      multivariate analysis, response to therapy, FeLV status, and clinical substage
      were predictive of outcome. FeLV-negative cats that achieved a complete response
      following induction therapy were likely to have durable (i.e., > 6-month)
      responses, particularly when doxorubicin was included in the chemotherapy
      protocol. However, FeLV-positive cats had significantly shorter remission and
      survival times with available chemotherapeutic protocols.

PMID- 9773413
TI  - Clinical and clinicopathologic features in 11 cats with Cuterebra larvae myiasis
      of the central nervous system.
AB  - The medical records of 11 cats with histopathologic findings consistent with
      central nervous system (CNS) Cuterebra larvae myiasis were retrospectively
      examined to determine if clinical features could identify this disorder
      antemortem. Young to middle-aged indoor-outdoor domestic shorthaired cats
      presenting with acute neurologic signs from July through September predominated.
      Many cats recently had clinical signs consistent with upper respiratory disease.
      Most cats presented for depression, lethargy, or seizures. Almost all cats had
      abnormal rectal temperatures, either hypethermia or hypothermia. Peripheral
      leukocytosis and eosinophilia were not characteristic of cats with CNS
      cuterebriasis. Cerebrospinal fluid analysis did not consistently disclose
      evidence of inflammation. Common neurologic deficits included blindness, abnormal
      mentation, and signs of unilateral prosencephalic disease. No specific clinical
      or clinicopathologic test was diagnostic for CNS cuterebriasis.

PMID- 9773412
TI  - Signal-averaged electrocardiograms in normal Doberman pinschers.
AB  - Signal-averaged electrocardiograms (SAECGs) were performed on nonsedated normal
      dogs in left-lateral recumbency. Following signal averaging, both time-domain and
      3-dimensional frequency-domain analyses were performed. For time-domain analysis,
      the high-frequency QRS (HFQRS) duration, duration of the terminal QRS complex
      less than 40 microV (LAS40), and root mean square (RMS) voltages (microV) of the
      terminal 40 milliseconds (RMS40) and 30 milliseconds of the QRS complex were
      calculated. For frequency-domain analysis, correlation ratios were calculated for
      30-, 40-, 50-, and 60-millisecond segment lengths begun 10, 15, or 20
      milliseconds before the end of the QRS complex. Spectro-temporal mapping was also
      performed. All of the parameters of the SAECGs analyzed in the time domain were
      associated with each other. LAS40 and RMS voltages regressed significantly (P <
      .0000) on the HFQRS duration. Ninety-five percent of the HFQRSs were 55-75
      milliseconds, 95% of the LAS40s were 9-26 milliseconds, and 95% of the RMS40
      voltages were 177-444 microV. None of the SAECGs contained evidence of
      ventricular late potentials. Spectro-temporal maps were similar in each dog when
      the same segment lengths and starting points were compared. No evidence of
      ventricular late potentials was observed. Correlation ratios were lower when
      windowed segments included 15 or 20 milliseconds (versus 10 milliseconds) of the
      terminal QRS complex. When only 10 milliseconds of the terminal QRS complex were
      included in windowed segments, the mean correlation ratios for 30- and 40
      millisecond segment lengths were > 0.8 and > 0.61 in 67% of all analyses,
      respectively.

PMID- 9773414
TI  - Resting and dobutamine stress echocardiographic factors associated with the
      development of occult dilated cardiomyopathy in healthy Doberman pinscher dogs.
AB  - In 29 healthy Doberman Pinschers, echocardiographic parameters evaluating
      systolic and diastolic function were examined prospectively at rest and during
      dobutamine constant rate infusion (5 micrograms/kg/minute) to determine if any
      parameters were associated with the development of occult dilated cardiomyopathy
      (DCM). A resting echocardiogram was repeated 1 year later to determine which dogs
      had met our criteria for occult DCM. Six dogs developed occult DCM during the
      follow-up period. Univariate logistic regression analysis showed that at rest, an
      increased left ventricular internal dimension in systole (LVID-S) (P = .02),
      preejection period (PEP) (P = .03), ratio of PEP to left ventricular ejection
      time (P = .02), and isovolumic relaxation time (P = .02) were significantly
      associated with the development of occult DCM. During dobutamine stress
      echocardiography (DSE), high LVID-S (P = .02) and systolic wall stress index (P =
      .04) and reduced fractional shortening (P = .02) and ratio of peak early to late
      diastolic mitral filling velocity (E/A) (P = .05) were associated with the
      development of occult DCM. Multiple logistic regression showed that LVID-S (P =
      .002) and E/A (P = .002) measured during dobutamine infusion also were associated
      with the development of occult DCM. Reclassification based on the DSE data was
      not significantly different than reclassification based on the resting
      echocardiographic data. Resting echocardiography and DSE have the potential to be
      clinically applicable screening tests for very early systolic and diastolic
      dysfunction in Doberman Pinschers, heralding the onset of occult DCM as it is
      currently defined.

PMID- 9773415
TI  - Gastric extramedullary plasmacytoma in a cat.

PMID- 9773416
TI  - Primary erythrocytosis in a 2-year-old Arabian gelding.

PMID- 9773417
TI  - Morphologic and molecular evidence of a dual species ehrlichial infection in a
      dog presenting with inflammatory central nervous system disease.

PMID- 9773418
TI  - Myotonic myopathy in a miniature Schnauzer: case report and data suggesting
      abnormal chloride conductance across the muscle membrane.

PMID- 9773420
TI  - Diagnostic approach to the child with hepatobiliary disease.
AB  - The purpose of this review is to present our approach to diagnosis of the child
      with liver disease. Since liver disease is relatively rare in pediatric practice,
      most clinicians lack experience with its diagnosis. Furthermore, diverse
      disorders can present with virtually identical findings because liver injury
      expresses itself in limited ways, particularly in the neonate. However, within
      the limited patterns of presentation, there is usually sufficient diversity to
      allow for discrimination and, therefore, differential diagnosis. Clinicians can
      use pragmatism and logic to achieve a systematic and practical approach to
      diagnosis. This approach uses a matrix that combines several simple parameters-
      the age at presentation, the dominant presenting findings, and a few well-chosen
      test--to arrive at a very limited differential. From that point, specific,
      focused investigations can confirm the diagnosis.

PMID- 9773419
TI  - Clinical vignette. Localization of focal intestinal bleeding using technetium
      labeled in vivo red blood cells in a dog.

PMID- 9773421
TI  - Liver development: a paradigm for hepatobiliary disease in later life.
AB  - The hepatobiliary system develops from a thickening of endothelial cells in the
      ventral part of the foregut. These cells form the hepatic and cystic diverticula,
      which undergo a series of events including cellular proliferation, migration, and
      differentiation to form the liver parenchyma and the ductular system. Studies in
      the developing liver suggest that surrounding mesoderm and ectoderm participate
      in the hepatic specification of the endoderm, and that transcription factors such
      as cJun, retinoblastoma gene, and nuclear factor kappa B are important regulators
      of liver embryogenesis. A review of the recent data on the role of transcription
      factors, growth factors, and cytokines in liver development provides insight on
      the ability of the liver to respond to injury and on the molecular basis of
      hepatobiliary diseases.

PMID- 9773422
TI  - Alpha-1-antitrypsin deficiency.
AB  - Homozygous PIZZ alpha 1-antitrypsin deficiency, which has an incident of 1 in
      1600 to 1 in 2000 live births, is the most common genetic cause of liver disease
      in children. It is also associated with chronic liver disease and hepatocellular
      carcinoma in adults. It is a well-known cause of pulmonary emphysema. Although
      emphysema is due to uninhibited proteolytic destruction of the connective tissue
      backbone of the lung, liver disease is thought to result from the toxic effects
      of the mutant alpha 1AT molecule retained within the endoplasmic reticulum of
      liver cells. Screening studies done by Sveger in Sweden have shown that only 10
      to 15% of the PIZZ population develop clinically significant liver disease over
      the first 20 years of life. Recent studies have suggested that a subgroup of PIZZ
      individuals are predisposed to liver injury because of an inefficient degradation
      of mutant alpha 1ATZ within the endoplasmic reticulum. Altered migration of the
      abnormal alpha 1ATZ molecule in isoelectric focussing gels is the basis of the
      diagnosis of alpha 1AT deficiency. Treatment of alpha 1AT deficiency-associated
      liver disease is mostly supportive. Liver replacement therapy has been used
      successfully for severe liver injury. An increasing number of patients with
      severe emphysema have undergone lung transplantation.

PMID- 9773423
TI  - Liver and biliary problems in cystic fibrosis.
AB  - Liver disease associated with cystic fibrosis has been increasingly diagnosed
      during recent years probably due to the combined effect of systematic hepatic
      assessment and reduced death from extra-hepatic causes of CF patients. In a group
      of 173 CF patients regularly followed at our Center, cumulative incidence of
      liver disease was 17% over a mean period of 10 years. Although it generally runs
      a mild course, it is considered a major complication of CF which may limit
      survival and quality of life of affected patients. CF-associated liver disease
      should be considered as the first inherited liver disorder in which the primary
      defect affects cholangiocyte transport systems. Although data assessing the
      effects of defective CFTR on cholangiocyte pathobiology are not yet available,
      the impaired secretory function of the biliary epithelium is considered
      responsible for reduced biliary fluidity and alkalinity and for subsequent bile
      duct damage by cytotoxic compounds or infectious agents. No clear association
      with specific CFTR mutations has been observed. Treatment with ursodeoxycholic
      acid, aimed at improving biliary secretion in terms of bile viscosity and bile
      acid composition, is currently the most useful therapeutic approach in CF
      associated liver disease. Beneficial effects on liver biochemistry, hepatic
      excretory function, liver histology, and essential fatty acid status have been
      reported, but no long-term data exist on its effectiveness on clinically relevant
      outcomes, such as death or need for transplantation. The effectiveness of bile
      acid therapy may be higher if started in patients with early stage liver disease,
      before symptoms have become clinically evident. Early diagnosis and
      identification of CF patients who are more liable to develop liver disease should
      be actively pursued.

PMID- 9773424
TI  - Disorders of the mitochondria.
AB  - Recent advances in our understanding of the structure and function of
      mitochondria have led to the recognition that inherited and acquired
      mitochondrial dysfunction may be responsible for diseases affecting the liver and
      other organ systems. Mitochondrial health may also determine hepatocyte survival
      in other hepatic disorders not directly related to the mitochondrion. Primary
      mitochondrial hepatopathies are conditions in which there are inherited defects
      in structure or function of the mitochondria, most of which involve the
      respiratory chain and oxidative phosphorylation, fatty acid oxidation, the urea
      cycle, and other pathways confined to mitochondria. Maternally inherited
      mutations or deletions of the mitochondrial genome, or putative nuclear gene
      mutations encoding electron transport proteins, cause defective electron
      transport, oxidative stress, impaired oxidative phosphorylation, and other
      metabolic derangements that lead to hepatic failure or chronic liver dysfunction
      in affected children. The mitochondrial DNA (mtDNA) depletion syndrome, which
      similarly leads to liver failure and neurologic abnormalities, is caused by a
      putative nuclear gene that controls mtDNA replication or stability. Other proven
      or suspected primary mitochondrial hepatopathies include Pearson's marrow
      pancreas syndrome, Alpers disease, mitochondrial neurogastrointestinal
      encephalomyopathy syndrome, and Navajo neuropathy. Secondary mitochondrial
      hepatopathies are conditions in which the mitochondria are major targets during
      liver injury from another cause, such as metal overload, certain drugs and
      toxins, alcoholic liver injury, and conditions of oxidant stress. Diagnosis of
      mitochondrial dysfunction may be difficult with currently available tools,
      however, elevated blood lactate: pyruvate ratios or arterial ketone body ratios
      with characteristic liver histology are initial tests. Measuring respiratory
      chain enzyme activities, mtDNA levels, and searching for mtDNA mutations and
      deletions are more specific tests. Treatment of these disorders is currently
      empirical, involving agents that may improve the redox status of mitochondria,
      promote electron flow, or act as mitochondrial antioxidants. Liver
      transplantation has occasionally been successful in patients who lack other
      systemic involvement.

PMID- 9773425
TI  - Nontransplant alternatives for the treatment of patients with metabolic disease.
AB  - Orthotopic liver transplantation is an accepted therapy for patients with acute
      and chronic liver disease including patients with hepatic based metabolic
      disease. In this review non-transplant options for the treatment of patients with
      liver disease including those with metabolic disorders are discussed.

PMID- 9773426
TI  - The intrahepatic cholangiopathies.
AB  - The intrahepatic biliary epithelial cells or cholangiocytes are the primary focus
      of injury in many congenital and acquired liver diseases of childhood. Although
      cholangiocytes account for only 3 to 5% of the liver cell population, injury and
      progressive loss of intrahepatic bile ducts can result in considerable morbidity
      and mortality. Table 1 provides an overview of the various disorders that affect
      the intrahepatic biliary tree. The more common disorders are discussed in detail
      below. One of the most important cholangiopathies, biliary atresia, characterized
      by complete destruction of the extrahepatic biliary tree, with variable
      involvement of the intrahepatic bile ducts, is discussed elsewhere in this series
      of articles. There has been considerable progress in our understanding of the
      embryology and physiology of the intrahepatic biliary system. These topics are
      also selectively reviewed, with an emphasis on advances that aid in the
      understanding of the pathophysiology of the disorders which affect the biliary
      tract in children.

PMID- 9773427
TI  - Immunological liver diseases in children.
AB  - Autoimmune liver diseases comprise a number of disorders in which inflammatory
      damage to the liver is believed to derive from an autoimmune attack. These
      include autoimmune hepatitis (AIH), characterised by positive smooth muscle
      and/or nuclear (SMA/ANA) or liver kidney microsomal type 1 (LKM1) antibodies,
      autoimmune sclerosing cholangitis (ASC), usually SMA/ANA positive, and AIH after
      liver transplantation, which is positive for SMA, ANA, or atypical LKM. These
      disorders often present with symptoms indistinguishable from prolonged acute
      hepatitis. Less commonly the onset is insidious, with nonspecific symptoms, or
      with complications of portal hypertension. For AIH and ASC, experimental evidence
      suggests that usually in individuals genetically predisposed to autoimmunity, a
      liver self antigenic peptide is recognized by T lymphocytes which promote a
      cascade of autoaggressive processes. For AIH after liver transplantation, the
      pathogenic mechanisms remain to be elucidated. All types of autoimmune liver
      disorders appear to respond favourably to early treatment with prednisolone with
      or without azathioprine. For patients presenting with fulminant hepatic failure
      or with already advanced cirrhosis, immunosuppression is rarely effective and the
      only mode of treatment is liver transplantation. The role of other
      immunosuppressant or immunomodulatory drugs, like cyclosporin A, tacrolimus or
      ursodeoxycholic acid, in the treatment of autoimmune liver disorders remains to
      be defined.

PMID- 9773428
TI  - Biliary atresia: pathogenesis and treatment.
AB  - Biliary atresia is a disorder of infants in which there is obliteration or
      discontinuity of the extrahepatic biliary system, resulting in obstruction of
      bile flow. Untreated, the resulting cholestasis leads to progressive conjugated
      hyperbilirubinemia, cirrhosis, and hepatic failure. Biliary atresia has an
      incidence of approximately one in 10,000 live births worldwide. Evidence to date
      supports a number of pathogenic mechanisms for the development of biliary
      atresia. An infectious cause, such as by a virus, would seem most pausible in
      many cases. The clinical observation that biliary atresia is rarely encountered
      in premature infants would support an agent acting late in gestation. However, no
      infectious or toxic agent has been conclusively implicated in biliary atresia.
      Genetic mechanisms likely play important roles, even regarding susceptibility to
      other specific causes, but no gene whose altered function would result in
      obstruction or atresia of the biliary tree has been identified. The variety of
      clinical presentations support the notion that the proposed mechanisms are not
      mutually exclusive but may play roles individually or in combination in certain
      patients. Biliary atresia, when untreated, is fatal within 2 years, with a median
      survival of 8 months. The natural history of biliary atresia has been favorably
      altered by the Kasai portoenterostomy. Approximately 25 to 35% of patients who
      undergo a Kasai portoenterostomy will survive more than 10 years without liver
      transplantation. One third of the patients drain bile but develop complications
      of cirrhosis and require liver transplantation before age 10. For the remaining
      one third of patients, bile flow is inadequate following portoenterostomy and the
      children develop progressive fibrosis and cirrhosis. The portoenterostomy should
      be done before there is irreversible sclerosis of the intrahepatic bile ducts.
      Consequently, a prompt evaluation is indicated for any infant older than 14 days
      with jaundice to determine if conjugated hyperbilirubinemia is present. If
      infectious, metabolic, endocrine disorders are unlikely and if the child has
      findings consistent with biliary atresia, then exploratory laparotomy and
      intraoperative cholangiogram should be done expeditiously by a surgeon who has
      experience doing the Kasai portoenteostomy. Biliary atresia represents the most
      common indication for pediatric liver transplantation, representing more than 50%
      of cases in most series. Transplantation is indicated when symptoms of end stage
      liver disease occur, including recurrent cholangitis, progressive jaundice,
      portal hypertension complications, ascites, decreased synthetic function, and
      growth/nutritional failure.

PMID- 9773429
TI  - Current concepts in pediatric liver transplant.
AB  - Orthotopic liver transplantation has significantly improved the survival rate of
      children with end-stage liver disease. Efforts to correct abnormalities existing
      prior to transplantation coupled with improved surgical techniques and
      immunosuppression have led to better quality of life and 1-year survival rates
      approaching 90% in many centers. Despite this success the expanding waiting list
      population of all ages has driven development of operative techniques to expand
      the donor pool. Building on the success of reduced-size transplantation, split
      liver and living-donor transplantation are now suitable alternatives, especially
      when used in candidates with satisfactory clinical stability. In the post
      operative period, infectious complications represent an important cause of
      morbidity and mortality. Although antimicrobial regimens are effective in the
      immediate post-operative phase, acquisition of viral infections represents a
      major concern particularly in the young liver recipient. Early detection and
      development of new anti-viral agents are likely to decrease occurrence of post
      transplant proliferative disorders and optimize longterm transplantation outcome.

PMID- 9773430
TI  - Screening for gonorrhea and chlamydia by DNA amplification in adolescents
      attending middle school health centers. Opportunity for early intervention.
AB  - GOAL: To determine prevalence and incidence of Neisseria gonorrhoeae (GC) and
      Chlamydia trachomatis (CT) infection and assess risk factors predictive for such
      infections in a middle school-based clinic sample. STUDY DESIGN: 170 female
      students and 43 male students making 256 and 47 visits, respectively, > or = 30
      days apart, in urban middle school clinics for primary care screening,
      reproductive health, or illness/injury were routinely asked to provide urine
      specimens for GC and CT ligase chain reaction testing if sexually active in the
      preceding 3-month period. Information regarding prior sexually transmitted
      diseases, reason for visit, and sexual risk behaviors was obtained. RESULTS: GC:
      11.4% of female student and 2.1% of male student tests were positive. Incidence
      was 34.0 cases/1,000 person months (95% Confidence interval [CI]: 19.5-67.5).
      Median time to first positive and repeat positive test was 4.6 and 2.6 months,
      respectively. For CT: 16.4% of female student and 2.1% of male student tests were
      positive. Incidence was 57.5 cases/1,000 person months (95% CI: 35.2-93.8).
      Median time to first positive and repeat positive CT test was 6.0 and 4.8 months,
      respectively. Assessed risk factors failed to specify a candidate screening
      population. CONCLUSION: These data suggest that all sexually active adolescent
      girls in this high risk setting should be offered testing for GC and CT at least
      twice per year, regardless of age or other sexual risk behaviors and that STD
      control efforts in high risk middle schools should be encouraged.

PMID- 9773431
TI  - Cost-effective screening for Chlamydia trachomatis: are DNA amplification assays
      the answer?

PMID- 9773432
TI  - Molecular subtyping of Treponema pallidum subspecies pallidum.
AB  - BACKGROUND AND OBJECTIVES: Epidemiologic studies on syphilis have been hampered
      by the fact that strains of Treponema pallidum subspecies pallidum (T. pallidum),
      the causative agent of this disease, cannot be differentiated by either protein
      based or deoxyribonucleic acid-based methods. Syphilis is endemic in many
      developing countries and is common in some industrialized nations. In addition,
      the disease has been shown to increase the risk of infection with the human
      immunodeficiency virus. GOAL: To develop a molecular subtyping method for T.
      pallidum. STUDY DESIGN: Two genes exhibiting intrastrain variability were
      identified as potential targets for strain differentiation: the acidic repeat
      protein (arp) gene, which contains a variable number of 60 base pair repeats, and
      a member of the treponema pallidum repeat (tpr) gene family. Polymerase chain
      reaction amplification and restriction endonuclease digestion of polymerase chain
      reaction products from laboratory strains and clinical specimens were used to
      develop a molecular subtyping scheme for T. pallidum. RESULTS: Determining the
      number of repeats in the arp gene by polymerase chain reaction resulted in 12
      different subtypes among the 63 isolates that were studied. Among those, most
      (54.2%) had arp genes with 14 repeats. The other 11 subtypes had arp genes with 7
      to 21 repeats, each accounting for 2% to 14% of the isolates. Polymerase chain
      reaction amplification of a member of the tpr gene family from a subset of 46
      isolates followed by digestion of the polymerase chain reaction product with MseI
      resulted in seven restriction fragment length polymorphism patterns designated a
      to g. Strains with 14 repeats could be grouped into five restriction fragment
      length polymorphism subtypes. By combining the two systems we observed 16
      subtypes among 46 isolates examined. This typing system is stable, reproducible,
      and easy to perform. In addition, the use of the ABI Genetic Analyzer for the
      determination of fragment size and banding patterns makes the results unbiased.
      CONCLUSION: This is the first molecular subtyping system that distinguishes among
      clinical isolates of T. pallidum.

PMID- 9773433
TI  - Continuing evolution of the pattern of quinolone resistance in Neisseria
      gonorrhoeae isolated in Sydney, Australia.
AB  - BACKGROUND AND OBJECTIVES: Multiple phenotypes of quinolone-resistant Neisseria
      gonorrhoeae isolated in Sydney since 1984 originated in Asia and increased in
      number and level of resistance in 1995. GOAL: To study the origins,
      characteristics, and infection pattern of quinolone-resistant Neisseria
      gonorrhoeae in Sydney from 1995 to 1997 and to compare these results with prior
      findings. STUDY DESIGN: Quinolone minimal inhibitory concentrations, phenotype,
      and geographic source of quinolone-resistant Neisseria gonorrhoeae isolated in
      Sydney from 1995 to 1997 were analyzed. RESULTS: Two hundred nineteen episodes of
      infection with quinolone-resistant Neisseria gonorrhoeae from 2,236 gonococcal
      isolates occurred during 1995 through 1997. The rate of isolation of quinolone
      resistant Neisseria gonorrhoeae increased significantly at the end of 1996 and
      was maintained through 1997. The increase resulted from sustained domestic
      transmission of a limited number of phenotypes in heterosexual patients.
      CONCLUSION: The pattern of isolation of quinolone-resistant Neisseria gonorrhoeae
      in Sydney changed from the sporadic isolation of multiple phenotypes of imported
      quinolone-resistant Neisseria gonorrhoeae to a higher rate of endemic disease
      caused by a few subtypes. Alterations in antibiotic treatment regimens in the
      affected patient group were required.

PMID- 9773434
TI  - False-positive enzyme immunoassay test results for Chlamydia trachomatis because
      of contact of the collection swab with agar.
AB  - BACKGROUND: We noted an increased incidence of false-positive Chlamydia
      trachomatis enzyme immunoassay results using the Abbott IMx SELECT C. trachomatis
      EIA test when a single swab was used for urethral sampling for both gonococcal
      culture inoculation and chlamydial detection. GOALS: To evaluate if contact of
      the enzyme immunoassay collection swab with an agar produces false-positive
      chlamydial enzyme immunoassay results. STUDY DESIGN: Samples containing agar
      based culture media were tested by two enzyme immunoassays and a ligase chain
      reaction technique. RESULTS: We report false-positive chlamydial enzyme
      immunoassay results using the Abbott IMx SELECT C. trachomatis EIA test if the
      collection swabs are in contact with gonococcal culture media (Modified New York
      City agar, chocolate, Thayer-Martin, or GC-lect) before insertion of the swab in
      the transport media of the enzyme immunoassay. The other assay results were
      negative. CONCLUSIONS: Using a single collection swab to screen for genital
      infections with gonococcal cultures and chlamydial enzyme immunoassay is
      inappropriate because it may lead to false-positive chlamydial enzyme immunoassay
      results, at least with the Abbott IMx SELECT C. trachomatis EIA test, incurring
      public health and financial consequences.

PMID- 9773435
TI  - 0.25% chlorhexidine gluconate gel. A protective topical microbicide.
AB  - BACKGROUND AND OBJECTIVES: An estimated 4 million new cases of chlamydial
      infection occur each year. This experiment assessed the effects of a vaginally
      applied gel formulation of 0.25% chlorhexidine gluconate on chlamydial infection
      and on the vaginal ecosystem. STUDY DESIGN: Twelve monkeys were treated with a
      single application of 0.25% chlorhexidine gluconate. These animals were assessed
      for changes in vaginal flora before and at 30 minutes, 1 day, and 2 days
      postapplication by microbiologic analysis. Cervical and vaginal tissues were
      assessed by colposcopy at each time point. Five monkeys received a single
      application of 0.25% chlorhexidine gluconate gel followed (30 minutes) by a
      cervical inoculation with Chlamydia trachomatis. Four monkeys were inoculated
      with Chlamydia only. Cervicovaginal tissues were assessed via modified
      colposcopy, vaginal swabs were collected for assessment of vaginal flora, and
      cervical swabs were collected for detection of Chlamydia (culture/ligase chain
      reaction) at baseline and days 1, 2, and 7 postinoculation. RESULTS: Changes in
      vaginal flora were minimal in all monkeys. Application of 0.25% chlorhexidine
      gluconate did not affect adversely vaginal colonization by lactobacilli. All
      chlamydial infection control monkeys were infected, whereas none of the five
      monkeys pretreated with chlorhexidine gluconate were positive for C. trachomatis
      by culture or ligase chain reaction. Colposcopic observations remained largely
      unchanged in all groups. CONCLUSIONS: A 0.25% chlorhexidine gluconate gel was
      protective against chlamydial infection in all animals tested, had no adverse
      effect on the vaginal flora, and had minimal effect on cervicovaginal tissues
      after a single application.

PMID- 9773436
TI  - Neisseria gonorrhoeae resistant to ciprofloxacin and ofloxacin.

PMID- 9773438
TI  - Contact tracing for genital Chlamydia trachomatis in a Swedish county.
AB  - BACKGROUND: Contact tracing is one of the measures used to control genital
      Chlamydia trachomatis infections. GOAL OF THIS STUDY: To assess important
      variables of contact tracing in an everyday clinical setting. STUDY DESIGN:
      Patients reported according to the STD Act were studied in a prospective,
      consecutive county-based study. RESULTS: A total of 149 patients had a mean of
      2.2 partners. The social worker's patients reported significantly more partners
      than the physicians' patients. The median number of patients at the 26 involved
      institutions was 3. Treatment without a prior examination was prescribed to 4% of
      the partners; 95% of all notified partners were examined, and a majority of them
      were chlamydia-infected. CONCLUSION: The requirements of the STD Act in Sweden
      are being followed reasonably well by health providers responsible for contact
      tracing, although an experienced social worker seems to get better results.

PMID- 9773437
TI  - Objective markers of condom failure.
AB  - BACKGROUND: Studies of condom efficacy rely on self-reported behavior. Objective
      markers of exposure to semen may provide a more valid assessment of condom
      failure and failure to use condoms. GOALS OF THIS STUDY: To compare three semen
      biomarkers: acid phosphatase (AP) activity, prostate specific antigen (PSA), and
      the human seminal plasma antigen (MHS-5). STUDY DESIGN: Twenty women were
      intravaginally inoculated with six measured, increasingly larger amounts of their
      partners' semen. Vaginal fluid was collected by the participant using swabs and
      tested. RESULTS: Background levels of PSA were low (0.00-1.25 ng/ml), background
      levels of AP were variable (0-350 U/l), and all preinoculation samples were
      negative for MHS-5. All postinoculation samples were positive for PSA, 64 of 117
      (55%) for AP, and 14 of 120 (12%) for MHS-5. CONCLUSION: The PSA immunoassay was
      the best semen biomarker under these sampling and testing conditions.

PMID- 9773439
TI  - Gender difference in persistent at-risk sexual behavior after a diagnosed
      sexually transmitted disease. ACSF-Investigators.
AB  - BACKGROUND AND OBJECTIVES: There are few data on sexual behavior after an episode
      of sexually transmitted disease (STD). GOALS: To examine association between a
      history of STD and subsequent at-risk sexual behavior in the general population.
      STUDY DESIGN: In the French National Survey of Sexual Behavior, current sexual
      behavior was compared between heterosexuals who reported an STD in the 4 years
      prior to the last year and those who reported no STD (n = 2517). RESULTS:
      Reporting of STD was associated with a high rate of past multiple partnership
      among both sexes, but was associated with current at-risk behavior in men only.
      Men with a previous history of STD were 2.8 times (95% confidence interval [CI]:
      1.4-5.6) more likely to report high-risk unprotected sex as a current behavior.
      No such association was observed in women (adjusted odds ratio [OR]: 1.0; 95% CI:
      0.5-2.0). Conversely, in women, a previous episode of STD was significantly
      associated with reporting of behavior changes (adjusted OR: 3.4; 95% CI: 1.6
      7.1). CONCLUSION: A self-reported history of STD is a marker of current high-risk
      sexual behavior among heterosexual men that could be used to target prevention
      programs. In contrast, it may be associated in women with subsequent adoption of
      STD and HIV risk reduction strategies.

PMID- 9773440
TI  - Sexually transmitted infections in women infected with the human immunodeficiency
      virus. Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA).
AB  - BACKGROUND AND OBJECTIVES: Limited prospective data are available on sexually
      transmitted infections (STIs) among HIV-infected patients. The incidence and
      predictors of STIs were assessed among HIV-infected women enrolled in a clinical
      trial. STUDY DESIGN: Prospective cohort of 323 women. RESULTS: Sixty-five percent
      had at least one STI based on history and/or examination at baseline. Most
      conditions identified at baseline were based on patient history; only 10 of 123
      women with no history of an STI (8.1%) had one identified upon examination.
      During a median follow-up of 2.1 years, 25% developed a new/recurrent STI. Being
      African-American (odds ratio [OR] = 4.22, 95% confidence interval [CI]: 1.45
      12.26), reporting sex with an intravenous drug user as an HIV risk behavior (OR =
      2.29, 95% CI: 1.34-3.92), and a history/presence of STIs at baseline (OR = 1.79,
      95% CI: 1.01-3.19) were factors associated with significantly increased risk of
      STI's. CONCLUSIONS: A substantial proportion of women developed new STIs during
      the course of the clinical trial. Prevention efforts should be emphasized among
      high risk HIV-infected patients.

PMID- 9773441
TI  - Bacterial pathogens in male patients with urethritis in Istanbul.

PMID- 9773443
TI  - Pathophysiological mechanisms of central neuropathic pain after spinal cord
      injury.
AB  - After spinal cord injury (SCI), between 10% and 20% of the patients may develop
      central neuropathic pain. This type of chronic pain usually is a very bothersome
      sequel and represents a major therapeutic challenge since conventional medical
      and surgical pain therapies generally are ineffective. This review focuses on
      recent advances in the understanding of the pathophysiology of this pain
      syndrome. Important clinical features of central neuropathic pain after SCI
      include loss of sensations mediated by spinothalamic pathways combined with
      development of abnormal pain perception (spontaneous continuous pain and
      abnormally evoked pain). Up-regulation of neuronal activity leading to
      spontaneous and evoked neuronal hyperactivity/hyperexcitability, may be the
      neurophysiological substrate for development of abnormal pain perception. This
      paper describes some neurochemical changes that may be important for the
      induction and maintenance of neuronal hyperactivity and abnormal pain perception:
      Increased excitatory glutaminergic activity involving N-methyl-D-aspartate (NMDA)
      receptor activation, may trigger the intracellular cascade reaction leading to
      upregulation of neuronal activity/excitability. Changes in voltage-sensitive Na+
      channels may contribute to changes in nerve membrane excitability. Other
      important mechanisms may be loss of endogenous inhibition, including reduced
      gamma-amino-butyric acid (GABA)ergic, opioid and monoaminergic inhibition. These
      various mechanisms may provide new targets for treatment of a pain syndrome that
      traditionally has been so difficult to handle.

PMID- 9773442
TI  - Use of self-collected vaginal swabs for detection of Chlamydia trachomatis
      infection.

PMID- 9773444
TI  - Antibodies to urinary tract pathogens in patients with spinal cord lesions.
AB  - Chronic or recurrent urinary tract infection (UTI) is a significant problem or
      patients with spinal cord lesions (SCL). UTIs are thought to be a major factor in
      the development of reduced renal function. To investigate the pathogenesis 151
      patients with SCL were included in this study during a 7 year period. Results of
      intravenous pyelography and isotope renography were recorded as well as the
      bladder emptying methods. One to seven blood samples were obtained from each
      patient and tested for plasma creatinine, and the presence of precipitating
      antibodies against Escherichia coli, Klebsiella pneumonia, Klebsiella ozaenae,
      Proteus mirabilis, Enterococcus faecalis and Pseudomonas aeruginosa. We found
      significant correlation between duration of SCL and precipitating antibodies
      against urinary tract pathogens (PAU) (r = 0.23, P < 0.005), between plasma
      creatinine and PAU in patients with spina bifida (r = 0.64, P < 0.01), between
      PAU and the number of positive urine cultures (r = 0.17; P < 0.05) and a relation
      between abnormal urological findings and PAU. In addition, the PAU was
      significantly higher in patients with indwelling urethral catheters (P < 0.001).
      Thus it seems that PAU can be of prognostic value in SCL patients, and PAU might
      be an indicator for intensified treatment of recurrent UTI.

PMID- 9773445
TI  - A quantitative study of genital skin flora and urinary colonization in spinal
      cord injured patients.
AB  - This study was performed to define the relation between colonization of genital
      skin flora and bacteriuria in spinal cord injured patients with neurogenic
      bladder dysfunction. Twenty-seven female and 23 male spinal cord injured patients
      were included in the study. Patients were evaluated regarding their type of
      bladder management, educational status, level and degree of the spinal cord
      lesion. Quantitative cultures were obtained from the perineum labium/dorsum of
      penis, external meatus of urethra, and urine. We investigated whether the
      organisms isolated from urine were also present in one or more skin sites in
      every patient. In total 54 identical bacterial isolates were observed both from
      urine and one or more skin sites in 43 of the patients. Escherichia coli, Proteus
      mirabilis, Klebsiella pneumoniae, and Proteus stuartii were the most common
      bacterial isolates. The distribution of identical colonization of genital skin
      flora with urine were as follows: 30 in urethra, one in perineum, four in urethra
      and perineum, nine in urethra and labium/dorsum of penis, and 10 in both three
      skin sites. Identical colonization of both perineum and labium/dorsum of penis
      with urine were significantly higher in female patients than those of males (P =
      0.037, P = 0.003, respectively). No significant difference was found in the
      presence/distribution of colonization with respect to type of bladder management,
      educational status, and neurologic status. These results demonstrate the
      importance of the urethra, perineum, and labium/dorsum of penis as a source of
      bacteria causing urinary infection in spinal cord injured patients.

PMID- 9773446
TI  - Obstructive sleep apneas in relation to severity of cervical spinal cord injury.
AB  - Thirty-three subjects (28 men, five women) with complete or incomplete cervical
      cord injury representing a wide range of neurological impairment were
      investigated with regard to the prevalence of Obstructive Sleep Apnea (OSA). The
      relation between OSA and neurological function, respiratory capacity, body mass
      index and symptoms associated with OSA were studied. Overnight sleep recordings
      employed combined oximetry and respiratory movement monitoring. Pulmonary
      function tests included static and dynamic spirometry, maximal static inspiratory
      and expiratory pressures at the mouth. The subjects answered a questionnaire
      concerning sleep quality and tiredness. The prevalence of OSA was 15% (5/33) in
      this nonobese cervical cord injury study population. Nine percent of the subjects
      (3/33) fulfilled the criteria for obstructive sleep apnea syndrome, but daytime
      sleepiness or fatigue were also common in subjects without OSA. There was an
      inverse correlation between oxygen desaturation index and American Spinal Injury
      Association (ASIA) motor score in the subjects with complete injury, while there
      was no such correlation in the whole study group. There were significant
      correlations between maximal inspiratory and expiratory pressures and vital
      capacity and between ASIA motor score and vital capacity.

PMID- 9773447
TI  - Surgery for cervical myelopathy in geriatric patients.
AB  - OBJECTIVE: The number of geriatric patients seeking surgical treatment for
      cervical myelopathy is steadily increasing. Although anecdotal experiences have
      been good, insufficient data exists in the spine literature concerning this
      particular group. We decided to review our experience to determine efficacy of
      surgical management and examine our morbidity with this select group. METHODS: We
      undertook a retrospective review of all surgical procedures for nontraumatic
      cervical myelopathy performed at Mt Sinai Medical Center and Jackson Memorial
      Medical Center between January 1 1987 and June 1 1992, in patients older than 70
      years of age (33 men and 18 women). RESULTS: A total of 53 cervical surgical
      procedures were performed in 51 patients (nine expansile laminoplasties, 20
      anterior cervical diskectomies and fusion and 24 decompressive posterior
      laminectomies). The average hospital stay was 7.7 +/- 3.4 days. Twenty-one (41%)
      patients required inpatient rehabilitation; the remaining 30 patients received
      outpatient rehabilitative therapy. The major morbidity rate was 3.9%, and the
      minor morbidity rate was 5.8%. Perioperative medical complications included
      cardiac arrhythmias, hypertensive episodes, atelectasis, confusion, urinary
      dysfunction and hyponatremia. All of these complications resolved except in one
      patient. The perioperative mortality rate was 2%. Office follow-up was performed
      for a mean of 11.1 +/- 2.5 months postoperatively. Comparison of preoperative and
      postoperative functional status was performed using Nurick's criteria as
      described in the literature. At follow-up, 60.8% of the patients had improvement
      in their myelopathic symptoms, especially in regard to gait; 33.3% were
      stabilized and 5.9% had worsened neurological function. CONCLUSION: This study
      demonstrates that corrective surgical procedures for significant nontraumatic
      cervical myelopathy in the geriatric population may be performed safely, that is,
      with acceptable risk of morbidity and reasonable expectation for clinical
      improvement.

PMID- 9773448
TI  - Risk of avascular necrosis following short term megadose methylprednisolone
      treatment.
AB  - We conducted a prospective cohort study to determine whether administration of
      large doses of the corticosteroid methylprednisolone following spinal cord injury
      as recommended in the National Acute Spinal Cord Injury Study-2 (NASCIS-2)
      protocol results in an increased incidence of avascular necrosis (AVN) of the
      femoral or humeral head. All subjects were patients treated by a spinal cord
      injury physician in an Acute Spinal Cord Injury Unit between 1989 and 1996 where
      some received the megadose steroids while others did not. Patients younger than
      15 years and older than 75 years were excluded, as were those with any hip or
      shoulder disease, with pelvic fracture, or with a history of predisposition to
      AVN by hip dislocation, excessive alcohol consumption, previous high dose steroid
      use, or systemic lupus erythematosus. Screening for AVN of the femoral and
      humeral heads was performed at a minimum of 6 months following injury, using
      magnetic resonance imaging (MRI). The films were read by a radiologist blinded to
      the treatment protocol received by the individual subject. Among the 59 spinal
      cord injured patients who received steroids (age 15-64 years (mean 32 years)),
      five were female. Among the 32 spinal cord injured subjects who did not receive
      steroids (age 16 to 65 years (mean 34 years)), seven were female. There was no
      case of AVN found in either group. Using binomial distribution, we conclude that
      the true incidence of AVN among the methylprednisolone treated group is less than
      5% (alpha < 0.05) and therefore continue to recommend short term (24 h)
      methylprednisolone therapy.

PMID- 9773449
TI  - DEXA: a practical and accurate tool to demonstrate total and regional bone loss,
      lean tissue loss and fat mass gain in paraplegia.
AB  - Persons with spinal cord injury lose lean tissue mass and bone but gain body fat.
      There is a need to quantify the magnitude of these changes in body composition
      because there are associated skeletal and cardiovascular health risks. We have
      compared total body and regional (lower limb) differences in body composition in
      a group of males with paraplegia and in healthy able-bodied males matched for
      age, and height using dual energy X-ray absorptiometry. Although patients and
      controls had similar body mass indices, significant reductions in lean tissue
      mass (16% less) and bone (12% less) were observed in those with spinal cord
      injury. Group differences were even more pronounced in the lower limb. DEXA also
      revealed large increases in fat mass in subjects who did not look obese, total
      fat mass being 47% higher in the paraplegic group. We suggest that DEXA provides
      a simple and practical means to quantify both whole body and regional changes in
      body composition associated with spinal cord injury.

PMID- 9773451
TI  - Influence of heterotopic ossification of the hip on bone densitometry: a study in
      spinal cord injured patients.
AB  - OBJECTIVE: To evaluate (1) the magnitude of falsely elevated bone density results
      caused by heterotopic ossification (HO) around the hip and (2) effect of age of
      patients when the measurement was taken, age of patients at injury, and age of
      injury (time since event) to the prevalence of HO. SUBJECTS AND METHODS: We
      blindly analyzed plain radiographs of the hip [(obtained within 1 month of dual
      energy X-ray absorptiometry (DEXA)] in 107 spinal cord injured (SCI) patients for
      HO and matched the result to the three regions of interest (ROI): the femoral
      neck, Ward's triangle, and the trochanter. The influence of HO on bone
      densitometric values was determined by the analysis of variance (ANOVA) and post
      hoc analysis. RESULTS: Nineteen (18%) patients had HO; overlying the femoral neck
      (79%), trochanter (74%) and Ward's triangle (37%), respectively. Significant
      elevation of densitometric values (P < 0.05 or less) was observed in a various
      magnitude at each ROI, with the greatest elevation at Ward's triangle. The
      prevalence of HO was high when the patients were injured at age range of 20-39
      years. CONCLUSIONS: HO around the hip can cause significantly elevated bone
      densitometry results at all ROIs, which can obscure underlying osteoporosis,
      leading to underestimation of fracture risk. Determination of bone density in
      this region with corresponding plain radiographs would be of help. In SCI
      patients, prevalence of HO was high when the age of patients at injury was 20-39
      years.

PMID- 9773450
TI  - Bone mineral status after pediatric spinal cord injury.
AB  - The impact of spinal cord injury (SCI) on later bone mineral status was studied
      in 35 adults who had sustained their injury in childhood. The median age of the
      patients was 31 years, the median age at injury 12.9 years and the median time
      period from injury was 19 years. The methods used in the study were clinical
      interview and examination, measurement of bone mineral density (BMD) of the
      lumbar spine and the proximal femur with dual energy X-ray absorptiometry (DEXA)
      and estimation of bone turnover with biochemical markers. The densitometric
      examination revealed that the BMD at the lumbar spine was within the normal range
      but grossly decreased in the femoral region. Moreover, there was a significant
      difference in BMD between patients with high (C2-T6) and low (below T6) lesions
      in the lumbar spine as well as in the femoral region. Patients with lower lesions
      had higher BMD values. The markers of bone turnover which were studied were serum
      and urinary calcium and phosphate serum alkaline phosphatase and its isoenzymes,
      osteocalcin, carboxyterminal propeptide of human type I procollagen (PICP),
      carboxyterminal telopeptide of type I collagen (ICTP) and urinary
      deoxypyridinoline. These markers of bone metabolism showed no signs of ongoing
      accelerated bone formation or resorption. The present study suggests that caution
      should be observed in weight bearing training or mobilisation of patients with
      pediatric SCI or perhaps with long standing SCI because of increased fracture
      risk. The prevention of dissociated osteoporosis should be investigated further
      in order to avoid fractures of weakened bones. The modes of prevention might be
      found in the use of modern pharmacotherapy of osteoporosis and from correctly
      dosage physical training.

PMID- 9773452
TI  - The effect of epidural cooling on lipid peroxidation after experimental spinal
      cord injury.
AB  - STUDY DESIGN: The effect of epidural space perfusion with chilled saline solution
      (% 0.9 NaCl) on lipid peroxidation after experimental spinal cord injury in rats
      was evaluated. OBJECTIVES: The extent of lipid peroxidation is a useful parameter
      for evaluating the cellular disturbance caused by spinal cord trauma in
      experimental conditions. The protective effects of hypothermia against
      neurological injury resulting from trauma or ischemia both in experimental and
      clinical situations have been demonstrated. SETTING: Departments of Neurosurgery
      and Biochemistry, Cerrahpasa Medical School, Istanbul, Turkey. METHODS: Twenty
      five female Wistar Albino rats were used. There were five rats in group I (sham
      operated), seven rats in group II (trauma), and eight rats in group III (epidural
      cooling). The remaining five rats were used for the pilot study to determine the
      spinal cord and body temperature. A clip compression method was used to produce
      acute spinal cord injury. In group III, 30 min after the trauma the injured
      spinal cord was cooled by perfusion of the epidural space with chilled saline
      solution (% 0.9 NaCl) with a flow rate of 5 ml/min for 30 min. At 2 h after
      trauma, all rats other than the ones used in the pilot study, were sacrificed and
      the spinal cords were excised. The extent of lipid peroxidation in the spinal
      cord was assessed by measuring the tissue content of malonil dialdehyde (MDA).
      RESULTS: The tissue MDA contents were 1.58 micromol MDA/gram wet weight (gww) in
      group I (sham-operated), 2.58 micromol MDA/gww in group 2 (trauma), and 1.77
      micromol/gww in group 3 (epidural cooling), the differences being statistically
      significant. CONCLUSION: The results indicated that epidural cooling of
      traumatized spinal cord is effective in preventing secondary damage due to the
      peroxidation of lipid membranes.

PMID- 9773453
TI  - Spinal epidural haematoma in a patient with haemophilia-B.
AB  - Spontaneous spinal epidural haematoma is rare. A case of haemophilia-B presenting
      with cervical spinal cord compression due to epidural haematoma, is reported.
      This is the second case in literature, to our knowledge, of intraspinal epidural
      haematoma in a patient with haemophilia-B. The importance of early diagnosis,
      especially with magnetic resonance imaging and surgical intervention, when deemed
      necessary, are emphasized.

PMID- 9773455
TI  - Post-traumatic syringomyelia and post-traumatic spinal canal stenosis.

PMID- 9773454
TI  - Plasmacytoma of dens as a cause of atlanto-axial instability.
AB  - A case of Plasmacytoma of dens (Odontoid Process) in an adult male managed by
      trans-oral excision and posterior fusion is reported for its rarity. The
      importance of neuro-imaging and the treatment options, in view of the associated
      instability at the atlanto-axial region and the difficulty in preoperative
      diagnosis are emphasized.

PMID- 9773456
TI  - Methodology for clinical trials in cancer patients with febrile neutropenia. Do
      we have a consensus?

PMID- 9773457
TI  - Intimacy and distance with patients with advanced cancer.

PMID- 9773458
TI  - Palliative care in Italy: the current situation.
AB  - Palliative care was initiated in Italy towards the end of the 1970s, mainly
      through the efforts of Professor Ventafridda and his colleagues. This article
      describes some of the most important steps made in this country to gain
      widespread acceptance for the principles and practice of palliative care. After
      about 15 years the Italian situation is still confusing. While some Regions have
      made progress, others are far from reaching even minimal goals. The efforts of
      many charities and of the Italian Society for Palliative Care and the Italian
      School for Palliative Medicine, have been huge, but still not sufficient to
      promote widespread involvement of the National Health Authorities. In the absence
      of clear Regional and central laws, the recent changes in the Italian health
      system combined with increasing financial difficulties threaten the advances
      already made.

PMID- 9773459
TI  - Cancer pain management in developing countries: a mosaic of complex issues
      resulting in inadequate analgesia.
AB  - Cancer pain is often undertreated even in developed countries with abundant
      resources and easy access to oral, parenteral, and transdermal opioids. The
      problems in developing nations are more complex, and as a result, these
      medications are not available to the vast majority of patients in Latin and South
      America, Eastern Europe, Asia, and Africa. Some of the reasons for this are
      reviewed, with India cited as a case example. In spite of serious efforts by the
      World Health Organization and other bodies to make oral opioids available and to
      educate government officials and physicians, little progress has been made in
      relieving pain in cancer patients in the developing world. Novel approaches that
      address fundamental concerns regarding opioid availability in these countries are
      desperately needed. One such approach, which is currently under development, is
      presented in this manuscript. This has the potential to make opioids available to
      patients in rural areas, improve compliance in the poorly educated patient,
      reduce the number of follow-up visits necessary for medication refills, and
      reduce the risk that opioids will be diverted to illicit channels. The potential
      for relieving cancer pain and the magnitude of this problem worldwide make it
      imperative that innovative approaches be tailored to the complex social issues
      and limited resources common to developing nations.

PMID- 9773460
TI  - Statistical considerations in clinical trials testing empiric antibiotic regimens
      in patients with febrile neutropenia.
AB  - The Chalmers scoring system for assessing the quality of randomized controlled
      trials was applied to 19 papers (published in 1976-1984) reporting the results of
      trials of antibiotics in febrile neutropenic patients, it was found at the time
      of this survey (publication 1986) that statistical issues were inadequately
      addressed in the papers and that the scoring system was a measure of the quality
      of reporting in the papers rather than the quality of the actual trials. Some new
      items have been added to the system to improve the validity of results, and 15
      more recent papers have been reviewed with reference to the updated scoring
      procedure, to find whether the quality of trials and of their reporting has
      improved since 1986. Further discussion of statistical issues in clinical trials
      is recommended.

PMID- 9773461
TI  - Criteria for response in patients in clinical trials of empiric antibiotic
      regimens for febrile neutropenia. Is there agreement?
AB  - A review of the literature on the criteria of response in patients on clinical
      trials of empiric antibiotic therapy revealed that there are at least three
      definitions utilized worldwide along with individual investigator definitions.
      The main definitions include definitions by Pizzo from the NCI, by the EORTC
      Antimicrobial group and by the Immunocompromised Host Society. The outcome in
      clinical trials can be affected by the definition used if the major endpoint in
      the study compares response rates of two or more initial empiric antimicrobial
      regimens for febrile neutropenia. Survival based definitions (Pizzo) are very
      useful but may not identify which regimen required the least number of
      modifications during the critical initial 3-5 days of trial. Evaluations later in
      the course of the febrile episode will not likely be influenced by these
      definitions as most patients with prolonged and severe neutropenia will
      eventually require modifications of therapy. A consensus to use a single response
      definition is necessary to allow comparisons and meta-analysis of results with
      specific antibiotic regimens for febrile neutropenia. These must be enforced by
      editors of major medical journals to truly allow this to happen.

PMID- 9773462
TI  - Empiric therapy for the febrile neutropenic patient. Design bias.
AB  - Empiric therapy is practical and must be begun promptly; the specific regimen
      chosen must be based upon local conditions and epidemiology. It must be recalled
      that subgroups of patients are not necessarily equivalent to the majority, i.e.,
      there are low-risk patients for whom ambulatory and/or oral therapy is
      appropriate and, conversely, there are high-risk patients who have a potential
      for a high mortality and who, while perhaps few in number, are of critical
      importance. Further, many of these patients are very complex, and this leads to a
      high level of physician concern and insecurity. This physician concern, in turn,
      leads to a tendency to modify regimens, given that the physician all too often is
      dealing with inadequate diagnostic information owing to the patient situation.
      The physician's choice of modification is highly dependent upon knowledge of the
      regimen the patient is already receiving. There is a need for clear definition of
      endpoints, and these must be established before the study is initiated. All too
      many published studies are too small to evaluate the endpoint that has been
      defined, and many others, although sufficient in size, have all of the problems
      inherent in studies conducted at multiple sites by multiple individuals with
      differing degrees of commitment or enthusiasm toward the study at hand. A few
      implications for study design and evaluation seem evident: it is critical to
      define endpoints and execute the study accordingly. This means determining the
      size of the population needed and determining the presence or absence of risk
      groups. Patients to be excluded e.g., those in whom infection is doubted must be
      selected on the basis of objective data by an observer blinded to both the
      outcome and the treatment. Similarly, the classification of response should
      preferably be done by an observer not influenced by knowledge of the therapy
      being given. Finally, and similarly, the decision to modify therapy (especially
      if modification is equivalent to defining failure with the regimen) should not be
      influenced by knowledge of the therapy being administered.

PMID- 9773463
TI  - Stratification in clinical trials of febrile neutropenia.
AB  - Patients with febrile neutropenia are characterized by well described prognostic
      factors leading to heterogeneity of risk of serious clinical outcomes. These
      prognostic factors complicate the design and interpretation of clinical trials of
      antimicrobial therapy in this population. Stratification is a method by which
      comparability of groups is ensured. This method can be employed prior to
      randomization or during the analysis. Factors that should be considered for
      stratification prior to randomization include the underlying neoplasm (leukemia
      vs solid tumor vs BMT), use of granulocyte growth factors, comorbid conditions
      and study site (in multicenter trials). In stratified analyses, trend in
      neutrophil count, site of infection, organism and susceptibility should be
      considered.

PMID- 9773464
TI  - Effect of carboplatin on response and palliation in hormone-refractory prostate
      cancer. Swiss Group for Clinical Cancer Research (SAKK).
AB  - To assess the efficacy of carboplatin in patients with hormone-refractory
      prostate cancer in terms of response rate and palliation, the Swiss Group for
      Clinical Cancer Research (SAKK) conducted this phase II clinical trial (SAKK
      08/91). Carboplatin 400 mg/m2 was administered i.v. every 28 days to 27 patients.
      The prostate-specific antigen (PSA) level was monitored and compared with the
      clinical response. Tumour response was evaluated according to EORTC criteria. For
      patients with nonmeasurable disease, response was defined as the absence of
      progression in any tumour localization, with no increase in PSA and a decrease of
      at least 2 points in the WHO pain score. Selected aspects of quality of life (QL)
      and use of analgesics were assessed to describe patients' experience of toxicity
      and palliation. Only 1 patient with measurable and 2 patients with nonmeasurable
      disease achieved partial remission or a response according to our criteria.
      However, 13 of the 27 evaluable patients had some benefit from carboplatin
      therapy, as indicated by an improvement in performance status, reduction of pain,
      and stabilization of metastases. There was no clear-cut association between
      clinical response and PSA level. QL data suggested that carboplatin was
      relatively well tolerated and confirmed the clinically documented palliation. In
      particular, from baseline, for at least two consecutive cycles 7 patients
      reported either an improvement in pain by 1 point or more on a 4-point scale (>
      or = 33%) without an increase in analgesic intake or a decrease by 50% or more in
      analgesic intake without an increase in pain. With the dose and schedule used in
      this study, carboplatin had only limited objective activity in advanced prostate
      cancer, but induced palliation in about half the patients.

PMID- 9773465
TI  - Tetanus immunity in patients with hematological malignancies.
AB  - The aim of this study was to investigate long-term immunity to tetanus toxoid
      among patients with hematological disease who had been treated with conventional
      doses of chemotherapy. Altogether 206 patients with different hematological
      malignancies were included in the study. There were marked differences between
      the rates of seronegativity against tetanus, varying from 20% to 70% in different
      groups of study patients. We found that 21 of 80 (36%) patients with AML, 45 of
      80 (56%) with ALL, 12 of 22 (54%) with lymphoma, 4 of 13 (31%) with myeloma and 2
      of 11 (18%) with CML were not immune to tetanus. In a multivariate logistic
      regression model increasing age (P = 0.0001), lymphoid malignancy (P = 0.0005)
      and advanced disease stage (P = 0.0001) were independent risk factors for loss of
      tetanus immunity in patients with hematological malignancies.

PMID- 9773466
TI  - Rationale for the use of a single fixed intravenous dolasetron dose for the
      prevention of cisplatin-induced nausea and vomiting. Pooled analysis of 14
      clinical trials.
AB  - Dolasetron mesilate is a selective 5-HT3 receptor antagonist that prevents
      chemotherapy-induced and postoperative nausea and vomiting. For the majority of
      patients in intravenous dolasetron trials for chemotherapy-induced nausea and
      vomiting, dosing has been based on body weight (mg/kg). The approved weight-based
      dose is 1.8 mg/kg based on results of controlled clinical trials. However, trials
      of dolasetron evaluating oral doses for prevention of chemotherapy-induced
      emesis, and intravenous doses for prevention and treatment of postoperative
      emesis have used a fixed milligram dose. To identify an appropriate intravenous
      fixed milligram dose for the prevention of chemotherapy-induced nausea and
      vomiting, this analysis was performed to derive efficacy results for fixed
      milligram doses from pooled results obtained with dosing based on body weight.
      Intravenous dolasetron doses for 1,598 patients treated on a mg/kg basis (0.3,
      0.6, 1.2, 1.8, 2.4, 3.0 and 5.0 mg/kg) in 14 clinical trials were converted to
      fixed milligram doses based on weight. Fixed-dose groups were established at
      doses of 50, 75, 100, 125, 150, and 200 mg. Doses less than or equal to the
      midpoint between two dose groups were included in the lower dose group. Pooled
      results showed that the 100 mg intravenous dolasetron dose group (who received
      actual doses of 88-112 mg) produced the highest rate (53%) of complete response
      (0 emetic episodes and no rescue medication in the 24-h period following
      initiation of chemotherapy).

PMID- 9773467
TI  - Competent gastrostomy for patients with head and neck cancer.
AB  - This study was performed to evaluate the efficiency and patient satisfaction with
      a modified Janeway gastrostomy for patients with head and neck cancer and cancer
      of the upper GI tract and involved 24 consecutive patients with serious
      malnutrition caused by advanced cancer of these sites. All underwent surgery
      during which a tube was constructed from the anterior gastric wall with the aid
      of GIA-75 automatic stapler. The operation was performed under local anaesthesia,
      with a senior anaesthesiologist, who sedated the patients, in attendance. The
      operation was successful in all cases. No postoperative mortality could be
      attributed to the operation. The complications were minor. The patient's close
      relatives were able to feed them intermittently with home-made formula made
      according to the instructions of our dietician. No late complications were
      recorded. Overall, the patients were satisfied with his technique for managing
      their feeding problem. The modified Janeway gastrostomy is an easy and safe
      operative procedure; it is an effective way of managing patients with
      malnutrition as a result of cancer of the head and neck or of the upper GI tract.

PMID- 9773468
TI  - Opioid responsiveness in patients with advanced head and neck cancer.
AB  - The degree of opioid responsiveness in patients with different pain syndromes
      associated with advanced head and neck cancer was studied with the aid of various
      indices that have proved to be easy to compare and capable of eliciting
      individual profiles of opioid responsiveness in cancer patients with pain. Thirty
      seven patients requiring opioid therapy for more than 6 weeks were reviewed. The
      opioid escalation index (OEI) was lower in aged patients, albeit not
      significantly. Significant differences in OEI were found among patients belonging
      to the different categories of responses proposed. Although higher doses were
      needed than reported in the general population, pain was considered acceptable
      and most patients were classified as partially responsive. Neuropathic pain was
      associated with higher OEIs. The indices applied will be useful in clinical
      research to demonstrate individual profiles of opioid responsiveness, from cases
      of easy and immediate pain control to unresponsiveness to opioid treatment, which
      can be difficult to evaluate in the clinical setting.

PMID- 9773469
TI  - Restriction endonuclease profiles of orf virus isolates from the British Isles.
AB  - A comparison of DNA profiles of representative isolates of orf virus, obtained
      using four different restriction endonucleases (RE), showed that the enzyme EcoRI
      could be used to discriminate between wild-type virus isolates and vaccine
      strains. The enzyme was used to compare the RE profiles of orf virus isolates
      from 43 outbreaks of orf that occurred in vaccinated flocks between 1988 and
      1993; 21 outbreaks yielded wild-type virus, 10 yielded vaccine viruses, three
      produced both vaccine and wild-type viruses and no clear result was obtained from
      nine of the outbreaks. From the 21 outbreaks yielding wild-type viruses, 28 orf
      virus isolates had clear RE profiles and 15 distinct RE profiles were recorded.
      Usually only one virus type was associated with each outbreak but from two farms,
      two different wild-type viruses were recovered. No predominant genotype was
      identified, with four RE profile types being recovered for more than one
      outbreak. From the more severe form of orf involving the buccal cavities of lambs
      only wild-type viruses were recovered, with at least four different genotypes
      being represented.

PMID- 9773470
TI  - Effects of simulated lairage conditions on the physiology and behaviour of pigs.
AB  - The responses of pigs to being driven and mixed together in lairage were
      investigated. Five groups of six and five groups of seven 70 kg pigs were
      transported for 40 minutes on a lorry and then subjected to one of the following
      treatments: two groups were driven down a passage; four groups (A to D) were
      mixed together for one hour (A and B together, and C and D together); and, four
      groups were driven down the passage and then mixed ('combined treatment'). The
      pigs' behaviour was recorded, skin damage was scored and saliva samples were
      taken for analysis of cortisol. The initial journey increased the pigs' salivary
      concentration of cortisol. Their behaviour while being driven was not correlated
      with the concentrations of cortisol after they were driven and cortisol
      concentrations did not increase relative to post-transport levels. The frequency
      and duration of fighting when they were mixed were positively correlated with
      their level of aggression in the home pen and with the increase in concentrations
      of cortisol when they were mixed. One hour after they had been mixed, the
      concentrations of cortisol had decreased relative to post-transport levels. After
      the combined treatment, the correlations observed for the mixing treatment were
      absent, and the concentrations of cortisol increased relative to post-transport
      levels. Skin damage was greatest after the groups of pigs were mixed. The
      responses observed indicate that the combined effects of driving and mixing,
      which are very common in lairage, were greater than the effects of driving or
      mixing alone.

PMID- 9773471
TI  - Neuropathological and aetiological studies of sporadic non-suppurative
      meningoencephalomyelitis of cattle.
AB  - Sporadically occurring non-suppurative encephalitis appears to be a frequent
      condition of Swiss cattle. Fifty-one such cases diagnosed over a period of 10
      years were examined retrospectively to investigate whether they constituted one
      or more distinct diseases, and to search for aetiological agents. Three cases
      were characterised by periventricular granulomatous encephalitis, and most
      probably represented a different disease, but the remaining 48 cases had
      disseminated non-suppurative encephalitis with widespread neuronal changes.
      Neuronal degeneration was very marked in the hippocampus of 10 cases and in the
      cerebellar Purkinje cells of 11. It was thought that the latter cases represented
      morphological variations of the same disease rather than a different disease
      because of their overlapping morphological features. The 48 cases had the
      following features in common: the disease had primarily neurological signs
      affecting mostly adult cattle, it was a sporadic condition, and there was a clear
      tendency for it to have a subacute to chronic course. Polymerase chain reaction
      (PCR) amplification for chlamydial DNA was negative except in one of 32
      specimens, and immunohistochemistry did not demonstrate the presence of
      chlamydial antigens either in the one PCR-positive case or in the other cases
      examined. Immunohistochemistry for rabies virus, Borna disease virus, and central
      European tickborne encephalitis virus was negative. In four cases, immunolabelled
      cells were found in the lesions with antibodies against paramyxovirus antigens.

PMID- 9773472
TI  - Experimental oral transmission of Ehrlichia phagocytophila to calves.
AB  - Three groups of four calves were used to determine whether Ehrlichia
      phagocytophila could be transmitted orally to calves via infected milk. Groups 1
      and 2 consisted of four-week-old calves and group 3 of newborn calves. The calves
      in group 1 were fed for several days with milk from cows infected experimentally
      with E phagocytophila. The calves in groups 2 and 3 were fed 200 ml of whole
      blood containing E phagocytophila organisms; for group 2 the blood was added to
      milk before being fed, and for group 3 the blood was added to colostrum before
      being fed within three hours after birth. Blood samples for haematological,
      serological and cytological examination, and for polymerase chain reaction (PCR)
      were collected from all the calves, starting on the first or only day of
      administration and then every four days for four weeks. The calves of groups 1
      and 2 showed no clinical, haematological or serological changes, and there was no
      direct or indirect evidence of the agent. In contrast, all the calves in group 3
      had mild pyrexia and seroconverted on day 8, and in one of them E phagocytophila
      organisms were visible in leucocytes, and the PCR on the buffy coat was positive
      on day 8.

PMID- 9773473
TI  - Effect of treatment with buffalo follicular fluid on ovarian function in goats.
AB  - Oestrus was synchronised in 15 nondescript goats with two injections of 7.5 mg
      luprostiol given 11 days apart. They were randomised into two groups; nine (group
      1) received 3 ml charcoal-extracted buffalo follicular fluid at 12 hour intervals
      on days 12 to 15 of the cycle and six (group 2) received an equal volume of
      normal saline at the same times. Luteolysis was induced 96 hours after the
      treatments began by a single injection of 7.5 mg luprostiol. The onset of oestrus
      was detected using a vasectomised buck and the ovarian response was determined by
      visual observation of the ovaries following a midventral laparotomy performed
      five or six days after oestrus. In the goats of group 1, oestrus occurred 99.3
      (4.13) hours after the injection of luprostiol, and in the goats of group 2 after
      68.0 (6.7) hours. Group 1 does had significantly more ovulations (2.56 [0.29])
      and large (> or = 5 mm diameter) unovulated follicles (2.77 [0.40]) than the does
      of group 2 which had 1.83 (0.16) ovulations and 0.50 (0.34) large unovulated
      follicles.

PMID- 9773474
TI  - Serum antibody in equine neonatal septicaemia due to Actinobacillus equuli.

PMID- 9773477
TI  - Stereotypic behaviour in kittens.

PMID- 9773476
TI  - Visitations to veterinary schools outside the UK.

PMID- 9773475
TI  - Prevalence of serotypes and toxin types of Actinobacillus pleuropneumoniae in
      pigs in Croatia.

PMID- 9773478
TI  - Vitamin D deficiency in a shar pei.

PMID- 9773479
TI  - Long-term follow-up after resectional surgery in patients with Crohn's disease
      involving the colon.
AB  - BACKGROUND: The majority of patients with Crohn's disease will eventually have
      colonic involvement, and more than 50% of these patients undergo resectional
      colonic surgery. The extent of colonic resection is discussed controversially.
      AIMS: We evaluated prognostic factors influencing the long-term outcome after
      resectional surgery including the colon. METHODS: We analyzed the postoperative
      course in 170 patients (mean follow-up 7.4 years) after first colonic surgery.
      Lifetable and multivariate factor analysis were performed to assess the influence
      of various factors on the postoperative long-term outcome. 85% of the patients
      had concomitant ileal disease, 40% had rectal disease, 48% percent of the
      patients had extensive colonic disease at the time of primary surgery. RESULTS:
      In 17% of the initial operations a colectomy was performed, the remaining 83%
      operations consisted in segmental colonic resections. The cumulative risks of
      clinical recurrence/reoperation were 63%/33% after ten years and increased by the
      presence of anal fistulas (relative risk 1.7/3.0) and after colocolonic type of
      anastomosis (relative risk 1.9/2.8). Ileal disease, rectal disease, extent of
      resection and pattern of colitis did not influence the recurrence rates. The risk
      to undergo completion colectomy was 11% ten years after segmental resection and
      not higher in the presence of extensive colonic disease. The risk of a definitive
      stoma was 11% after ten years and higher after ileorectal anastomosis (25% versus
      8% after segmental resection: p < 0.003). CONCLUSION: Colocolonic type of
      anastomosis and the presence of anal fistulas are risk factors for recurrence
      after initial colonic resection. Segmental resections were not followed by
      increased recurrence rates or a higher stoma rate. To maintain colonic length and
      intestinal continuity segmental colonic resection is the treatment of choice in
      patients undergoing surgery for local complications, even in the presence of
      extensive colonic disease.

PMID- 9773480
TI  - p-ANCA target antigens in ulcerative colitis.
AB  - INTRODUCTION: Data about the nature and pathophysiological relevance of the
      target antigens reacting with perinuclear antineutrophil cytoplasmatic
      autoantibodies (p-ANCA) in ulcerative colitis are inconsistent and partly
      conflicting. In the majority of the previous studies only one singular potential
      target antigen was investigated. The present study aimed on the simultaneous
      assessment of five different p-ANCA subtypes in patients with ulcerative colitis
      and attempted to detect reactivity against one of the previously described
      antigens and to correlate specificity for different target antigens with clinical
      features of the disease. METHODS: Sera from 61 patients with ulcerative colitis
      and from 56 healthy controls were tested using indirect immunofluorescence and
      enzyme-linked immunosorbent assays specific for elastase, lactoferrin, cathepsin
      G, myeloperoxidase and bactericidal permeability increasing protein (BPI). p-ANCA
      subtypes were correlated with clinical features of ulcerative colitis like
      disease extent or presence of extraintestinal manifestations. Moreover, a
      possible correlation to current immunosuppressive therapy was evaluated. RESULTS:
      In 46% (28/61) of patients with ulcerative colitis and in 4% (2/56) of the
      controls p-ANCA were detected. p-ANCA subtypes were distributed as follows: 26%
      (16/61) anti-BPI. 16% (10/61) anticathepsin G, 15% (9/61) antielastase, 7% (4/61)
      antilactoferrin, 5% (3/61) antimyeloperoxidase. Presence of anticathepsin G
      antibodies was negatively correlated with immunosuppressive therapy. No further
      correlations between p-ANCA subtypes and clinical characteristics were observed.
      DISCUSSION: p-ANCA subtypes in inflammatory bowel disease react with a variety of
      different target antigens and are not correlated with clinical features of the
      disease.

PMID- 9773481
TI  - [Pica in Germany--amylophagia as the etiology of iron deficiency anemia].
AB  - Pica (pica = magpie) is an eating disorder that is manifested by a craving for
      oral ingestion of a given substance that is unusual in kind (nonfood items) or
      quantity (food items). Pica has been described as a world wide phenomenon, but
      there are more frequent occurrences of selected substances among selected groups-
      especially young children and black pregnant and nonpregnant women in the
      southern part of the USA. In Central Europe and Germany this syndrome has not
      been described in the moderne literature. For this reason, we report a case of
      pica for starch associated with severe iron deficiency anemia in Germany. Iron
      deficiency anemia and--less often-potassium and zinc deficiency are the main
      complications of an excessive starch or clay ingestion, followed by
      gastrointestinal obstructions due to gastroliths or impaction. Additionally,
      naphtalene poisoning (in pica for toilet air-freshener blocks), phosphorus
      poisoning (in matches pica), mercury poisoning (in paper pica), and lead
      poisoning (in dried paint pica) have been described.

PMID- 9773482
TI  - Cure of autoimmune gastritis by Helicobacter pylori eradication in a 21-year-old
      male.
AB  - BACKGROUND: More recent investigations have shown that in some patients
      Helicobacter pylori (Hp) antibodies can act as antigastric antibodies and lead to
      atrophic autoimmune gastritis of the oxyntic mucosa. The question thus arises as
      to whether this form of autoimmune gastritis can be healed by eradicating Hp.
      METHODS: Case history of a 21-year-old man with active autoimmune gastritis of
      the oxyntic mucosa with lymphocytic infiltration of the entire lamina propria,
      foci of lymphocytic destruction of a number of glands, and hypertrophy of the
      preserved parietal cells, but no signs of Hp in the Warthin Starry stain. The
      search for parietal cell antibodies and intrinsic factor antibodies proved
      negative, while the level of the gastrin in the serum was slightly elevated.
      Since the presence of Hp IgG antibodies (243 U/ml) was confirmed. Hp eradication
      therapy was carried out. RESULTS: 15 months after Hp treatment the Hp IgG
      antibody titre had decreased to 11 U/ml. The autoimmune gastritis had healed, and
      autoaggressive inflammatory infiltrates with focal destruction of corpus glands
      and hypertrophy of the parietal cells were no longer detectable. CONCLUSIONS:
      Autoimmune gastritis induced by Hp may possibly be cured with Hp eradication
      treatment; to confirm this, further controlled prospective studies are needed.

PMID- 9773483
TI  - Cell proliferation and its evaluation in the colorectal mucosa: effect of
      ethanol.
AB  - Colorectal cell turn over is affected by numerous factors including diets,
      alcohol consumption, smoking or age and is also significantly changed in certain
      mucosal diseases including benign and malignant tumors. Mucosal hyperregeneration
      is associated with an increased cancer risk since it increases the susceptibility
      of the mucosa towards the action of carcinogens. The measurement of colorectal
      mucosal regenerativity can be used for risk assessment in carcinogenesis. For the
      evaluation of colorectal regeneration in vivo and in vitro methods exist. The
      most accurate and elegant in vivo method is the metaphase arrest technique which
      is a dynamic measurement of cell turn over using vincristine to arrest metaphase
      figures. This method is limited to animals. In man, colorectal biopsies can be
      incubated with tritiated thymidine or with bromodeoxyuridine and thereafter the
      incorporation of the two compounds into DNA can be visualized by autoradiography
      or by immunohistology. More recent developments include the use of antibodies
      against certain proteins which are closely related to certain phases of the cell
      cycle and which are expressed in dividing cells. The most frequently used
      proteins are proliferative cellular nuclear antigen (PCNA) and Ki-67 which are
      visualized by immunohistology in routinely fixed histological specimens. Finally,
      in situ hybridization of histone H3 mRNA which is almost exclusively expressed
      during S-phase, has been established as an excellent method for the determination
      of colorectal cell regeneration. In conclusion, chronic alcohol consumption both
      in animals and in man leads to mucosal cellular hyperregeneration, possibly
      secondary to mucosal injury, most likely due to acetaldehyde. The acetaldehyde is
      produced mainly by fecal bacteria and may exert its toxicity by mechanisms still
      unknown, possibly involving a direct effect on DNA. The ethanol-associated
      mucosal hyperregeneration is closely related to carcinogenesis since chronic
      ethanol ingestion leads to an increased risk of cancer in the colorectum.

PMID- 9773484
TI  - Glucose metabolism in vivo in crossbred Holstein cattle feeding on different
      types of roughage during late pregnancy and early lactation.
AB  - An experiment was carried out to study the glucose kinetics of crossbred Holstein
      cattle feeding on either hay or 5% urea treated rice straw during late pregnancy
      (21 days prepartum) and early lactation (30 days postpartum). In all 16 pregnant
      heifers (23-25 months of age) were selected for the experiments, including eight
      animals of two breed types, Holstein Friesian x Red Sindhi (50:50 = 50% HF) and
      Holstein Friesian x Red Sindhi (87.5:12.5 = 87.5% HF). They were divided into
      four groups of four animals each. Animals from the same breed type in each group
      were fed with either rice straw treated with 5% urea or pangola hay (Digitaria
      decumbens) as the source of roughage throughout the experiments. The glucose
      turnover rate in both types of crossbred Holstein cattle was determined using a
      continuous infusion of [U-14C] and 3-[3H]glucose during late pregnancy and early
      lactation. Total glucose entry and utilization rates increased significantly
      during lactation for all groups. Recycling of [C]glucose was, approximately 20%
      in both crossbred cattle fed either hay or urea treated rice straw and was
      unaffected by the stage of late pregnancy or early lactation. Comparing 50 and
      87.5% HF animals, arterial plasma glucose concentrations were slightly higher
      during pregnant periods but significantly higher in lactating periods in 50% HF
      animals. The ratio of specific radioactivity of arterial blood bicarbonate
      relative to that of arterial blood [14C]glucose in the lactating period,
      significantly decreased in 50% HF animals fed either urea treated rice straw or
      hay. An increase in udder blood flow during early lactation was significantly
      higher in 87.5% HF animals than in 50% HF animals. The uptake, arteriovenous
      differences and extraction ratio for glucose across the udder, significantly
      increased in the lactating period for all crossbred animals. Glucose uptake by
      the udder of 87.5% HF animals accounted for 65% of the total glucose turnover
      rate compared to a value of 46% in the lactating 50% HF animals. It can be
      concluded that both crossbred cattle fed either urea treated rice straw or hay
      exhibit the same body glucose turnover rate. The 87.5% HF animal has the genetic
      potential for a high milk yield and has high body and udder glucose metabolisms
      compared with 50% HF animals.

PMID- 9773485
TI  - Activity of cellulolytic enzymes in the contents of reticulorumen and caecocolon
      of roe deer (Capreolus capreolus).
AB  - Selective ruminants, which prefer easily digestible plants, cannot digest fibrous
      forage as well as grass eaters. Low enzyme activity or short retention time of
      ingesta particles in fermentation chambers appeared to be responsible for reduced
      cellulose breakdown. Seasonal activity of cellulolytic enzymes, cellulose
      concentration and protozoa population in reticulorumen (RR) and caecocolon (CC)
      of roe deer as a typical concentrate selector were investigated. Cellulase
      activities were lowest in winter when cellulose concentration in RR contents were
      highest. Highest enzyme activities and lowest cellulose concentration were
      measured in early spring. Cellulolytic activities were significantly correlated
      with the number of protozoa in RR. Only one entodinomorphic genus was identified
      in the RR. The enzyme activities in CC were far lower compared with those in RR.
      Low cellulose digestion in the RR cannot be compensated for by cellulose
      breakdown in the CC. The reduced cellulose digestion of roe deer may be
      attributed to the short retention time of food particles in spring and summer,
      whereas decreased colonisation of microorganisms in the rumen may be the main
      reason for low cellulose breakdown in winter.

PMID- 9773486
TI  - Daily milk intake and body water turnover in suckling mink (Mustela vison) kits.
AB  - Daily (24 h) milk intake and body water turnover were measured in eight litters
      of suckling mink (Mustela vison) kits (6-9 kits litter-1) during weeks 1-4 post
      partum using the tritiated water (3HHO) dilution technique. The biological half
      life of body water turnover in the mink kits increased linearly from 0.9 days in
      week 1 (3-5 days post partum) to 1.9 days in week 4 (22-24 days post partum). The
      daily milk intake varied markedly among the mink kits within a litter and
      increased significantly with increasing body mass from (mean +/- SEM) 10.9 +/-
      0.4 g per kit during week 1 to 27.7 +/- 1.0 g per kit during week 4. Throughout
      the study, male kits were approximately 10% heavier and had a significantly
      higher milk intake than female kits. The results were corrected for water
      recycling between the dam and her kits, ranging from approximately 4 to 15% of
      the daily milk water intake, and the calculated daily milk yield of the 2 year
      old lactating mink dams increased from 87 +/- 7 g day-1 in week 1 to 190 +/- 15 g
      day-1 in week 4 post partum. The average body growth rate of the mink kits ranged
      from 2.9 g kit-1 per day in week 1 to 5.4 g kit-1 per day in week 4, and the
      calculated mean intake of mink milk per unit of body weight gain was remarkably
      stable at 1.0 (g g-1) during weeks 1-3 post partum, but increased to 5.6 (g g-1)
      in week 4 post partum. The amount of metabolizable energy supplied to the kits by
      the daily milk yield of the dam increased from approximately 450 to approximately
      990 kJ day-1, which corresponded well with the calculated daily energy
      requirements of the kits. The tritiated water dilution technique was found
      feasible and reliable for repeated measurements of milk intake in suckling mink
      kits up to 4 weeks of age.

PMID- 9773487
TI  - Lysine and glutamate transport in the erythrocytes of common brushtail possum,
      Tammar Wallaby and eastern grey, kangaroo.
AB  - It was recently coincidentally discovered, using 1H NMR spectroscopy, that the
      erythrocytes of two species of Australian marsupials, Tammar Wallaby (Macropus
      eugenii) and Bettong (Bettongia penicillata), contain relatively high
      concentrations of the essential amino acid lysine (Agar NS, Rae CD, Chapman BE,
      Kuchel PW. Comp Biochem Physiol 1991;99B:575-97). Hence, in the present work the
      rates of transport of lysine into the erythrocytes from the Common Brushtail
      Possum (Dactylopsilia trivirgata) and Eastern Grey Kangaroo (Macropus giganteus)
      (which both have low lysine concentrations), and Tammar Wallaby were studied, to
      explore the mechanistic basis of this finding. The concentration-dependence of
      the uptake was studied with lysine alone and in the presence of arginine, which
      may be a competitor of the transport in some species. In relation to GSH
      metabolism, glutamate uptake was determined in the presence and absence of Na+.
      The data was analysed to yield estimates of the maximal velocity (Vmax) and the
      Km in each of the species. Erythrocytes from Tammar Wallaby lacked saturable
      lysine transport in contrast to the other two species. The glutamate uptake was
      normal in all three animals for adequate GSH biosynthesis.

PMID- 9773488
TI  - Physiological significance of behavioral hypothermia in hypoglycemic frogs (Rana
      catesbeiana).
AB  - Hypoxia elicits a number of compensatory responses in animals, including
      behavioral hypothermia. The hypothesis that hypoglycemia induces hypothermia in
      the bullfrog Rana catesbeiana was tested and that this behavioral response would
      be beneficial. Frogs equipped with a temperature probe were tested in a thermal
      gradient (10-40 degrees C). Insulin (15 IU kg-1) caused significant reduction of
      body temperature, from 25.0 to 17.8 degrees C. A non-metabolizable glucose
      analogue, 2-deoxy-D-glucose (2-DG, 50 mg kg-1), which blocks intracellular
      glucose utilization, was also injected and caused a similar drop in body
      temperature, despite an increase in plasma glucose levels. To assess the possible
      benefits of hypoglycemia-induced hypothermia, the effects of insulin and 2-DG
      injections were measured on plasma glucose concentration and on oxygen
      consumption of frogs equilibrated at 10, 20 and 30 degrees C. The plasma glucose
      was elevated at higher temperatures and so was oxygen consumption. The insulin
      caused a significant reduction of plasma glucose concentration (about 1.22 muMol
      ml-1) whereas 2-DG caused a significant increase (about 0.70 muMol ml-1) at 30
      degrees C. Both drugs caused a reduction of oxygen consumption (approximately
      0.388 and 0.382 ml min-1 kg at 30 degrees C after insulin and 2-DG injection,
      respectively). No effect of either insulin or 2-DG was observed when the animals
      were equilibrated at 10 degrees C. In conclusion, hypothermia may be a beneficial
      response to hypoglycemia in frogs.

PMID- 9773489
TI  - Fucoxanthin metabolites in egg yolks of laying hens.
AB  - Feeding experiments were conducted with White leghorn laying hens fed a
      carotenoid depleted control diet (containing some zeaxanthin and lutein) or this
      diet supplemented with 15% seaweed meal of established carotenoid composition.
      Egg yolk colour was estimated by use of a Roche Yolk Colour Fan and by detailed
      quantitative and qualitative carotenoid analysis of individual eggs of three
      laying hens during 4 weeks. Identification of the carotenoids included HPLC. VIS,
      MS, 1H NMR data and partial synthesis. The results confirmed that fucoxanthin,
      the major carotenoid in seaweed meal, is not transferred to the yolk. However,
      fucoxanthin gave rise to the metabolites fucoxanthinol, fucoxanthinol 3'-sulphate
      and paracentrone, that are ascribed to enzymatic modifications occurring in the
      hens. The difuranoid auroxanthin encountered in the egg yolk was ascribed to
      violaxanthin and/or its furanoid derivatives present in the seaweed meal. Colour
      of individual yolks varied considerably. The pigmentation level is discussed.

PMID- 9773490
TI  - Diving seals, ischemia-reperfusion and oxygen radicals.
AB  - The cardiovascular adaptations of seals that contribute to their ability to
      tolerate long periods of diving asphyxial hypoxia result in episodic regional
      ischemia during diving and abrupt reperfusion upon termination of the dive. These
      conditions might be expected to result in production of oxygen-derived free
      radicals and other forms of highly reactive oxygen species. Seal organs vary
      during dives with respect to the degree and persistence of ischemia. Myocardial
      perfusion is reduced and intermittent; kidney circulation is vigorously
      vasoconstricted. Heart and kidney tissues from ringed seals (Phoca hispida) and
      domestic pigs (Sus scrofa) were compared in reactions to experimental ischemia.
      Resulting production of hypoxanthine, indicative of ATP degradation, was higher
      in pig than in seal tissues. Activity of superoxide dismutase (SOD), an oxygen
      radical scavenger, was higher in seal heart. We suggest that these results
      indicate enhanced protective cellular mechanisms in seals against the potential
      hazard of highly reactive oxygen forms. SOD activity was unexpectedly higher in
      pig kidney.

PMID- 9773491
TI  - Influence of daylength on metabolic rate and daily water loss in the male
      prosimian primate Microcebus murinus.
AB  - In its natural habitat, Microcebus murinus, a small malagasy prosimian primate,
      is exposed to seasonal shortage of water and resources. During the winter dry
      season, animals enter a pronounced fattening period with concurrent decrease in
      behavioural/physiological activities, whereas the breeding season is restricted
      to the rainy summer months. To determine the role of daylength on metabolic rate
      and water loss in this nocturnal primate, we measured body mass, oxygen
      consumption at 25 degrees C (RMR), circadian water loss through urine output (UO)
      and evaporation (EWL) in eight males exposed to either short days (8L:16D SD) or
      long days (14L:10D LD), under controlled captive conditions. Exposure to SD led
      to a ponderal increase (maximal body mass: 125 +/- 4 g, N = 8), and to
      significant changes in RMR and water loss, both reaching lowest values after 3
      months under SD (0.84 +/- 0.04 ml O2 h-1 g-1 and 38 +/- 0.3 mg H2O g-1 day-1,
      respectively). Following exposure to LD, body mass decreased to 77 +/- 3 g (N =
      8), whereas both RMR and water loss, mainly through EWL, significantly increased
      (P < 0.001), the highest value occurring after 2 months (1.51 +/- 0.08 ml O2 h-1
      g-1 and 87 +/- 7 mgH2O g-1 day-1, respectively). Moreover, independent of
      daylength, circadian changes in EWL were characterized by significantly reduced
      values during the diurnal rest. The results demonstrate that daylength variations
      affect the physiology of this tropical primate, allowing anticipatory adaptation
      to seasonal environmental constraints.

PMID- 9773492
TI  - Leucine transport in Xenopus laevis oocytes: functional and morphological
      analysis of different defolliculation procedures.
AB  - L-leucine uptake in stage V Xenopus laevis oocytes was affected by the specific
      methods used to remove the follicle cells. In the presence of 100 mM NaCl, L
      leucine uptake was reduced by 67.5% +/- 5.7 when defolliculation was performed
      enzymatically by collagenase treatment, whereas the reduction was 30.5% +/- 6.4
      after mechanical defolliculation. The Na(+)-dependent uptake of 0.1 mM L-leucine
      was 18.6 +/- 4.6 pmol oocyte-1 40 min-1 in folliculated oocytes and 5.6 +/- 1.9
      in collagenase defolliculated oocytes (means +/- SE). L-leucine uptake was not
      affected by the removal of the follicular layer if defolliculation occurred after
      the transport period; radiolabeled L-leucine is therefore not taken up into a
      compartment that is removed by the defolliculation process. The different L
      leucine uptake rates observed in folliculated and defolliculated oocytes were not
      due to non-specific L-leucine binding to membranes. L-leucine kinetics showed
      that the L-leucine Vmax and Km values were lower in oocytes deprived of the
      follicular layer than in control oocytes enveloped in intact follicular layers.
      The Vmax and Km values of Na(+)-dependent L-leucine transport, calculated from
      data obtained the day after defolliculation by collagenase treatment, were: 16 +/
      1.5 pmol oocyte-1 40 min-1 and 57 +/- 21 mumol (mean +/- SD). The Na(+)
      activation curve of 0.1 mM L-leucine was hyperbolic in folliculated oocytes and
      sigmoidal in defolliculated oocytes. The morphological analysis performed in
      parallel with the transport experiments showed that after defolliculation, the
      fibers forming the vitelline membrane tended to be arranged in a more regular
      orthogonal array, and the number of oocyte microvilli was reduced after
      collagenase treatment. Mechanical defolliculation did not appreciably affect the
      oocyte microvilli, however this procedure did not completely remove all follicle
      cells. The damage to collagenase treated oocytes was reversible, and the
      functional and structural features of most oocytes improved upon subsequent in
      vitro incubation. The recovery process seemed to involve protein synthesis in
      view of the increased value of L-leucine Vmax, and microscopic observation
      showing recovery of the microvillar apparatus.

PMID- 9773494
TI  - The thermodynamics and evolution of complexity in biological systems.
AB  - Recent advances in nonequilibrium thermodynamics leads to the conclusion that
      similar processes, constrained by the second law of thermodynamics, give rise to
      the emergence of structure and process in a broad class of dissipative systems.
      The second law suggests that, in systems moved away from equilibrium, processes
      can emerge so that the system organizes in a way that reduces the effect of the
      applied gradient. If dynamic and or kinetic conditions permit, self organization
      processes can be expected. As biosystems grow and develop, they should increase
      their total dissipation, and develop more complex structures with more energy
      flow, increase their cycling activity, develop greater diversity and generate
      more hierarchical levels. As a corollary to this general statement, biosystems
      which do not increase their total dissipation, are organisms dedicated to death,
      like observed during the aging of any biosystem. Species which survive in
      ecosystems are those that funnel energy into their own production and
      reproduction and contribute to autocatalytic processes which increase the total
      dissipation of the ecosystem while at same time surviving within the constraints
      of their changing environment. In a broad class of biosystems, stress and aging
      have similar thermodynamic properties and suggests common underlying principles.

PMID- 9773493
TI  - Heterogeneous cholinergic reactions of ringed seal coronary arteries.
AB  - Coronary blood flow of some seal species is unusual in that it is highly variable
      in both non-diving and diving conditions and shows intermittent fluctuations,
      especially during dives when it frequently ceases for brief periods. We sought
      regulatory mechanisms governing these reactions by studying isometric tension
      recordings of isolated left circumflex (LC) and left anterior descending (LAD)
      coronary arteries of ringed seals, Phoca hispida, during reactions to a variety
      of agents for stimulating or blocking autonomic responses of the vascular smooth
      muscle. Micromolar acetylcholine (ACh) produced constriction of the small
      diameter segments of the LAD, but relaxation of the LC and larger segments of
      LAD. Both constrictions and dilations were prevented by atropine. Small vessel
      constriction by ACh was prevented by micromolar indomethacin and by a thromboxane
      receptor antagonist. Large vessel ACh dilations were prevented or reduced by
      rubbing off the endothelium and by the L-arginine analog, L-NG-nitro-arginine, an
      inhibitor of nitric oxide synthesis. We conclude that cholinergic, muscarinic,
      dilation of ringed seal large coronary arteries is mediated by endothelial
      derived relaxing factor (EDRF), whereas ACh constriction of small arteries is
      mediated by a prostaglandin.

PMID- 9773495
TI  - Cell membranes; barriers, regulators and transducers?
AB  - The concept of the cell membrane as a physical barrier has been progressively
      revised over the past 50 years to produce a model of a homeostatic regulatory
      system. Homeostatic feedback systems involve control and feedback transducers,
      with error detecting systems. It is, therefore, interesting to see how far the
      control of membrane fluidity, cell volume and ion composition can be interpreted
      in this way especially in epithelial systems. An attempt is made to consider the
      systems involved in extracellular, intracellular and stored calcium. When
      membranes are analysed in this way it is possible to identify questions about the
      extent to which cell regulation and cell transport might be in conflict, and how
      specific some membrane functions might be. These can then be related to the study
      of various adaptations to environmental stresses.

PMID- 9773496
TI  - Effect of different environmental variables on the synthesis of Hsp70 in
      Raphidocelis subcapitata.
AB  - Heat-shock proteins (Hsp) or stress proteins are strong candidates for biomarkers
      of environmental pollution since they are activated very early in the cascade of
      cellular events that follow toxic exposure and at concentrations below the lethal
      dose. Included in a test battery comprised of different bioassays, Hsp induction
      could provide a general purpose tier I indicator of pollution. Still, little is
      known on the induction of Hsp under different environmental conditions. In the
      present study we have made use of an Enzyme Linked Immunosorbent Assay (ELISA) to
      detect the synthesis of Hsp70 in Raphidocelis subcapitata in response to changes
      in pH, temperature, humic acids, nitrates and phosphates. The results show that
      algae respond to these changes in the environment by a transient increase in
      Hsp70 levels, the extend of which is dependent on the actual parameter under
      investigation. Out of these five parameters studied, only temperature and
      possibly pH were able to induce acquired tolerance, i.e. algae grown at a pH or
      at a temperature different from control conditions were shown to have acquired
      resistance to a subsequent challenge with Zn (10(-5) M). Adjustment of the pH and
      temperature in two physico-chemically different natural surface waters was
      demonstrated to be sufficient to obtain similar induction patterns of Hsp70 upon
      exposure to zinc. These results qualify Hsp70 as a good biomonitor for
      environmental pollution provided essential environmental parameters such as pH
      and temperature are kept constant.

PMID- 9773497
TI  - Heat shock protein (hsp70) in brown trout epidermis after sudden temperature
      rise.
AB  - So far, hsp70 has not yet been studied in the fish skin. This organ has a
      potential as an indicator organ and we investigate whether hsp70 could be used as
      a biomarker. In this study, we examined whether and how the epidermis reacts to a
      temperature rise. Brown trout, Salmo trutta fario, were exposed to higher
      temperature for 2 h and were allowed to recover subsequently. Samples were taken
      from controls, after heat shock, as well as after 24 and 48 h of recovery. The
      occurrence of hsp70 in trout skin was examined by Western blot. The amount of
      hsp70 was higher after 2-h heat shock and was rising until the end of the
      experiment. Immunocytochemically, hsp70 was detected in epidermal filament cells.
      After 2-h heat shock, hsp70 was predominantly located in the nucleus. At this
      time, light and electron microscopy revealed several features known to occur
      under a variety of stressors. Ultrastructurally, the appearance of compact
      filament aggregates in pavement cells was remarkable. After 24 h of recovery,
      filament compaction was lacking and after 48 h aspects of regeneration were
      obvious. However, an increased amount of apoptotic cells in the epidermis was
      prominent at this time only.

PMID- 9773498
TI  - The fate of organic xenobiotics in aquatic ecosystems: quantitative and
      qualitative differences in biotransformation by invertebrates and fish.
AB  - Biotransformation of natural and man-made foreign compounds (xenobiotics)
      proceeds via introduction of a functional group (phase I metabolism) and
      subsequent attachment of a polar moiety to the group (phase II metabolism). The
      biotransformation fate of xenobiotics depends on the activities, complement and
      inducibility of the biotransformation enzymes. Previous analysis of the
      dependence of in vivo rates of biotransformation on tissue parent compound
      concentration for marine invertebrates revealed that hydrocarbons are metabolised
      more slowly than xenobiotics already containing functional groups, and
      crustaceans metabolise both types of xenobiotics faster than molluscs
      (Livingstone D.R., Persistent pollutants in marine ecosystems, pp. 3-34,
      Pergamon, Oxford). Use of the same approach showed that fish metabolise
      pentachlorophenol (PCP) and benzo[a]pyrene (BaP) faster than certain aquatic
      invertebrates, viz. rates of biotransformation to total metabolites (pmol min-1 g
      1 wet wt.) at a tissue parent compound concentration of 10 nmol g-1 were,
      respectively, 19.2 +/- 3.7 (Carassius auratus) and 4.8 +/- 6.6 (molluscan
      species) (PCP), and 19.1 +/- 6.3 (fish species) and 2.1 +/- 0.2 (crustacean
      species) (BaP). The higher rate of biotransformation of BaP in fish is consistent
      with higher levels of total cytochrome P450 and inducible cytochrome P4501A
      (CYP1A) activity. The similar rate of metabolism of a hydrocarbon (BaP) (requires
      initial metabolism by cytochrome P450) and a functional group compound (PCP) by
      fish may also be due to the high levels of cytochrome P450, compared with the
      situation in invertebrates where rate-limiting cytochrome P450 may be responsible
      for the lower rates of hydrocarbon compared with functional group compound
      metabolism.

PMID- 9773499
TI  - Effects of chronic exposure to PCBs on cytochrome P450 systems and
      steroidogenesis in liver and testis of bulls (Bos taurus).
AB  - Effects of chronic exposure to PCBs on the microsomal cytochrome P450 (CYP)
      enzymes in liver and testis of bulls (Bos taurus) were determined by comparing
      the constitutive and PCB-induced alkoxyresorufin O-dealkylase and testosterone
      hydroxylase activities. Specific inductions of the prevailing hepatic
      ethoxyresorufin O-deethylation and 6 beta-hydroxylation of testosterone are
      suggestive of the induction of CYP1A1 and CYP3A-like enzymes by PCBs. A high
      level of PCB-inducible androstenedione formation was also found. The hepatic
      CYP2B activities (i.e. pentoxyresorufin O-depentylase and testosterone 16 beta
      hydroxylase) and CYP2C11-like testosterone 2 alpha-hydroxylase were increased
      only weakly. The testicular microsomal CYP activities were non-specifically
      reduced by the PCB exposure, except for the androstenedione formation and 16 beta
      hydroxylation of testosterone. The inhibition of the activity of mitochondrial
      CYP11A, as the rate-limiting enzyme of steroidogenesis measured with resorufin 3
      beta-hydroxy-22,23-bisnor-5-cholenyl ether as the fluorogenic substrate, exceeded
      50% in testes of the PCB-contaminated bulls. The latter activity as well as the
      hepatic testosterone 6 beta-hydroxylation and hepatic and testicular
      androstenedione formation may significantly contribute to the decrease in
      testosterone levels after the PCB intake.

PMID- 9773500
TI  - Inhibition and activation of the thyroidal axis by the adrenal axis in
      vertebrates.
AB  - Hormones of the adrenal or interrenal axis and stress situations which induce
      elevated glucocorticoid plasma levels (e.g. handling and starvation), inhibit
      thyroid function in growing and adult vertebrates. However, data indicate that
      during foetal and embryonic development (mammals and birds) or during larval
      growth and metamorphosis (fish and amphibians), the adrenal axis may stimulate
      thyroid function. Recent findings have provided some information concerning this
      stimulatory interference of the adrenal axis. In amphibians corticotropin
      releasing hormone and not thyrotropin releasing hormone is thyrotropic during
      metamorphosis, thus providing the substrate T4 necessary for T3 production. Other
      data indicate that the increase in plasma T3 at metamorphic climax may be the
      result of an inhibition of the T3 degrading activity, rather than stimulation of
      the T4 into T3 converting activity, and that glucocorticoids may be responsible
      for this. Also, in the chick embryo glucocorticoids effectively increase plasma
      T3 concentration by reducing the hepatic T3 degrading activity, whereas
      corticotropin releasing hormone also induces an elevation in the thyrotropin
      plasma levels and hence raises T4 concentrations which may function as a
      substrate for T3 production.

PMID- 9773501
TI  - Thermoregulatory responses of mesic and xeric rodent species to photoperiod
      manipulations.
AB  - Thermoregulatory mechanisms in rodents were found to respond to photoperiod
      manipulations. In desert adapted species, non-shivering thermogenesis NST
      capacity (the ratio between the maximal VO2 response to noradrenaline injection
      and RMR, measured 1 degree C below the lower critical point) increased, as due to
      long scotophase acclimation. The aim of the present study is to compare the
      thermoregulatory responses of mesic rodents with those of desert ones, to
      photoperiod manipulations. Heat production, body temperature and NST were studied
      in the Levant vole, Microtus guentheri, the Migratory hamster, Cricetulus
      migratorius, and the Macedonian mouse, Mus macedonicus, acclimated to long
      (16L:8D) and short (8L:16D) photoperiod regimes at a constant ambient temperature
      of 25 +/- 1 degree C. The results of our study show that the three mesic species
      did not significantly change their NST capacity due to increase in the dark
      hours, as observed in desert species. However, in all three mesic species the
      increase in photophase resulted in a better resistance to high ambient
      temperatures by elevating the higher critical point and decreasing metabolic
      rates at the thermoneutral zone.

PMID- 9773503
TI  - Does chronic hypoxia increase rat carotid body nitric oxide?
AB  - The carotid body plays an important role in ventilatory adaptation during chronic
      hypoxia. Nitric oxide (NO) may act as a regulator in neurotransmission,
      influencing the carotid body chemosensory discharge. The aim of the study was to
      understand if NO could contribute to the adaptation process during chronic
      hypoxia. The rats were kept in chronic hypoxia (10-11% inspired oxygen) for 12
      days, while the controls were kept in room air (21% O2). The distribution for
      diaphorase activity and immunohistochemistry for nitric oxide synthase (NOS)
      showed that chronic hypoxia induces an increase in NOS activity in the carotid
      body. It was concluded that NO release increased during chronic hypoxia and
      causes an inhibitory effect on carotid chemosensory discharge of the rat carotid
      body.

PMID- 9773502
TI  - Role of retinoic acid in regulation of mRNA expression of CaBP-D28k in the
      cerebellum of the chicken.
AB  - In contrast to vitamin D3-dependent gene expression of calbindin (CaBP-D28k) in
      intestine and kidney, the cerebellar mRNA expression seems independent of vitamin
      D3. The present study was conducted to elucidate correlation of mRNA expression
      of CaBP-D28k and vitamin D3 receptor (VDR) in the kidney and cerebellum of the
      developing chick by Northern blot analysis, localization of CaBP-D28k mRNA within
      the cerebellum by in situ hybridization, and effect of retinoic acid in ovo on
      CaBP-D28k mRNA levels. CaBP-D28k mRNA levels were low in the cerebellum until
      embryonic day 16 (E16) but markedly increased on E18 and reached plateau levels
      on E20. VDR mRNA levels were low until E16 and significantly increased on E18 but
      decreased on E20 and remained low on 1 and 7 days after hatching. In the
      mesonephros, CaBP-D28k mRNA levels were high until E16 but abruptly decreased on
      E18, while VDR mRNA levels remained relatively constant throughout the examined
      period between E10 and 20. In situ hybridization analysis clearly demonstrated
      CaBP-D28k mRNA signals within the Purkinje cells of the cerebellum in the embryo
      on E12-E18. Although 1.25 dihydroxyvitamin D3 [1.25(OH)2D3, 3 x 10(-10) M
      injected in ovo on E15 increased CaBP-D28k mRNA levels in the mesonephros on E16
      but had no effect on those in the cerebellum. On the contrary, in ovo injection
      of retinoic acid (10(-10) and 10(-8) M) caused no effect on CaBP-D28k mRNA levels
      in the mesonephros but significantly increased those in the cerebellum. The
      results indicate a regulatory role of retinoic acid on mRNA expression of CaBP
      D28k in the cerebellar Purkinje cells of the chicken embryo.

PMID- 9773504
TI  - Effect of propofol on perception of pain in mice: mechanisms of action.
AB  - The latencies of pain threshold to different subhypnotic doses (12.5, 25 and 50
      mg kg-1) of propofol, an anaesthetic, administered intraperitoneally (i.p.) into
      male mice were measured using a hot plate method. The possible mechanism of pain
      control by propofol was also investigated through blocking beta-endorphin
      receptors and measuring serum level of beta-endorphin. Morphine (1.5 mg kg-1;
      i.p.) was used as a reference of reduction of pain sensation. The results showed
      that propofol in doses of 25 and 50 mg kg-1 significantly (P < 0.01) increased
      the latency of pain threshold but a lower dose (12.5 mg kg-1) failed to produce
      any significant change. This indicates that propofol reduced pain and this effect
      is dose-dependent. Propofol prevents hyperalgesia produced by prostaglandin PGE2,
      (0.5 mg kg-1, i.p.; P < 0.01). Pretreatment with naloxone (1.0 mg kg-1, i.p.)
      abolished significantly (P < 0.01) the antinociceptive action of propofol.
      Furthermore, serum level of beta-endorphin was increased (P < 0.01) after
      propofol injection particularly at the peak time of propofol action. The serum
      level of corticosterone was also increased (P < 0.01) at the time of beta
      endorphin release. It was concluded that propofol can control pain and this
      action may be centrally modulated through the opioid system rather than at the
      level of the spinal cord.

PMID- 9773505
TI  - Ovarian, uterine and brain mast cells in female rats: cyclic changes and
      contribution to tissue histamine.
AB  - Using histochemical techniques, we determined mast cell content in ovarian,
      uterine and brain tissues throughout the estrus cycle of the rat. In one series
      of experiments, 26 cycling female rats were used for the measurement of follicle
      stimulating hormone (FSH) in plasma and evaluation of mast cells in the tissues.
      In a second series, cycling female rats were used for the determination of tissue
      histamine. The number, degranulation pattern and staining characteristics of mast
      cells changed synchronously in rat ovarian, uterine and brain tissues during the
      estrus cycle. A great majority of mast cells in tissues were stained by Alcian
      blue at proestrus and metestrus. Safranin-stained mast cells were abundant in all
      tissues during estrus and diestrus. Alcian blue-stained mast cells contribute to
      the change of tissues histamine level. In ovarian tissue, histamine level
      increased significantly at proestrus and metestrus. The lowest ovarian histamine
      level was determined at estrus, in which virtually all mast cells were stained by
      safranin only. Mast cells in ovarian, uterine and brain tissues seem to change
      their histamine content throughout the estrus cycle. Mast cells are absent from
      the thalamus during proestrus and are present in the hypothalamus only during the
      estrus phase. Plasma FSH concentrations (mlU ml-1) did not significantly change
      throughout the estrus cycle (proestrus: 0.81 +/- 0.11, estrus: 0.69 +/- 0.07,
      metestrus: 0.82 +/- 0.13, diestrus: 0.67 +/- 0.19).

PMID- 9773506
TI  - Accumulation of polyunsaturated fatty acids by concentrate selecting ruminants.
AB  - Depot fat samples from ruminants of different feeding type and--for comparison-
      fat samples from simple-stomached animals were collected within 3 months.
      Individual fatty acid proportions, especially the relation of essential,
      polyunsaturated fatty acids to nonessential, saturated plus monounsaturated fatty
      acids were analyzed by gas chromatography. Species can be separated into two
      distinct groups: Depot fat of wild boar showed by far the highest content of
      essential fatty acids compared with all ruminant species. The subsequent inter
      ruminant comparison yielded a further separation into two distinct groups related
      to feeding type. Roe deer and moose, constituting the first group of concentrate
      selectors, showed significantly higher percentages of polyunsaturated fatty acids
      than the other ruminant species comprised of the grass and roughage eaters or
      intermediates. The data document that the mode of feeding and/or the diet affects
      the body composition of the species investigated and that the depot fat
      composition of these ruminant species is markedly related to feeding type.

PMID- 9773507
TI  - Long-term pharmacological kindling increases in vitro release of IR-Met and IR
      Leu-enkephalin from amygdala.
AB  - Met-enkephalin release is increased from amygdala and striatum 1 and 15 days
      after pharmacological kindling with pentylenetetrazol, following potassium
      induced depolarization in vitro via a Ca2+ dependent mechanism. Leu-enkephalin
      release was only enhanced in amygdala and striatum 1 day after the last seizure.
      IR-Met-enkephalin amygdala tissue content enhanced 1 and 15 days after seizure.
      In striatum, we found an IR-Met-enkephalin decrease 35 days after the last
      stimulus. IR-Leu-enkephalin amygdala tissue content enhanced 1 day after the last
      seizure, and no significant increases were found in striatum 1, 15 and 35 days
      after the last seizure. In this paper, we show that opioid peptides release is
      differentially enhanced in rat brain for several days after the last seizure,
      thus suggesting that opioid peptides may have a protective action against seizure
      activity.

PMID- 9773508
TI  - Effects of adrenergic and cholinergic drugs on splenic arteries and veins from
      hooded seals (Cystophora cristata).
AB  - Isolated ring preparations of arteries and veins from hooded seal spleens were
      subjected in vitro to adrenaline (A), noradrenaline (NA), isoprenaline (Iso), and
      acetylcholine (ACh), alone or in combination with the blockers phentolamine
      (Phe), propranolol (Pro), and atropine (Atr). Both arteries and veins constricted
      in response to A (the estimated effective dose required for half-maximal response
      (ED50) was 3.3 and 0.2 microM, for arteries and veins, respectively) and NA
      (estimated ED50 was 1.5 and 0.6 microM, for arteries and veins, respectively),
      but these effects were abolished when the drugs were given in combination with
      the alpha-adrenoceptor blocker Phe. The responses of arteries and veins to ACh
      and the beta-adrenoceptor agonist Iso were minor and inconsistent, and were
      completely abolished when combined with their respective blockers (Atr and Pro,
      respectively). The ED50 for both A and NA are quite high in relation to normal
      plasma levels of A and NA in seals. This implies that these vessels (and, hence,
      the supply of blood to the spleen) primarily are subjected to neurogenic, rather
      than humoral physiological control.

PMID- 9773509
TI  - Response of the parotid gland of the brushtail possum, Trichosurus vulpecula, to
      adrenergic stimulation.
AB  - Adrenergic stimulation of parotid secretion was investigated in anaesthetised
      brushtail possums to ascertain fluid secretion rates and salivary composition.
      Because neither alpha- nor beta-adrenergic stimulation evoked saliva output,
      infusion of the adrenergic agonists was superimposed on a pre-existing
      bethanechol-stimulated flow. Isoprenaline infusion (2.4 nmol min-1) increased
      salivary amylase activity, [protein]; [HCO3]; [PO4] and [Ca], and amylase/Ca and
      protein/Ca ratios; reduced [Cl]; [K] and osmolality; but did not alter H+
      activity; [urea]; [Na]; [Mg]; amylase/protein or saliva/plasma urea ratios. These
      data are consistent with isoprenaline stimulating acinar secretion of protein, Ca
      and PO4 but not the ion transport necessary for primary fluid formation at the
      endpieces and modifying transport of monovalent ions in the excurrent ducts.
      Consequently, the possum parotid has beta-adrenergic receptors in both the
      endpieces and excurrent ducts. Phenylephrine infusions at 2.4 and 24 nmol min-1
      were without effect whereas phenylephrine at 240 nmol min-1 caused changes in
      salivary composition which paralleled those for isoprenaline administration but
      were generally of lesser magnitude. Thus, the possum parotid has few or no alpha
      adrenergic receptors and the salivary response elicited was the result of cross
      reaction of phenylephrine with beta-adrenergic receptors.

PMID- 9773510
TI  - Various light source treatments affect body and skeletal muscle growth by
      affecting skeletal muscle satellite cell proliferation in broilers.
AB  - In this study we addressed the effect of various monochromatic light treatments
      on muscle growth and satellite cell proliferation in broilers (Gallus
      domesticus). Broilers were reared under green (560 nm), blue (480 nm) and red
      (660 nm) monochromatic lights and white light as a control from day one until 35
      days of age. At five days of age, satellite cells were prepared from the
      experimental chicks. The number of satellite cells per gram of breast muscle and
      total number of satellite cells derived from the experimental broilers was
      substantially higher in the groups reared under green and blue light, compared to
      the red and white light groups. Growth hormone receptor gene expression was also
      higher in the former groups. High correlation was found between the breast muscle
      weight observed on day 35 and the number of satellite cells per gram of breast
      muscle (r = 0.915) and total number of satellite cells (r = 0.833), derived from
      the experimental chicks as early as five days of age. In addition, the
      protein/DNA ratio found in breast muscle at 35 days of age was significantly
      lower in chicks that were reared under green and blue lights. The lowest ratio
      which was found in the green group and was twice as low as in the control group,
      indicates the highest number of nuclei in the former group. As satellite cells
      are the only source of additional nuclei in skeletal muscles of postnatal
      animals, our results suggest that the higher muscle weight found in the green and
      blue light groups was due to increased satellite cell proliferation during the
      first days of age.

PMID- 9773511
TI  - Impact of exogenous amino acids on endogenous amino compounds in the fluid
      compartments of the chicken embryo.
AB  - Plasma, allantoic and amniotic fluid of the 13-day chicken embryo contain
      numerous free amino acids and related compounds. Of these, 40 were investigated
      using an HPLC-fluorometric technique. The concentration differences of the amino
      compounds between the fluid compartments are maintained by three bidirectional
      barriers, i.e. a blood/allantoic barrier, a blood/amnion barrier and an
      allantois/amnion barrier. Intraallantoic injection of 4.5 mumol/egg of asparagine
      (ASN), aspartic acid (ASP), valine (VAL) or serine (SER) revealed a strong
      allantois/blood barrier for these compounds. In contrast, there was equilibration
      between allantoic and amniotic fluid for ASN, ASP and SER, and an upward trend of
      the VAL concentration in the amniotic fluid, due to an 'overspill' from the
      allantois. The injections also affected endogenous amino compounds in all three
      fluid compartments. Asparagine had the most varied effects, including a strong
      drop of ten plasma amino acids. After all four types of injection, a number of
      endogenous amino compounds equilibrated between allantois and the normally
      hyporegulated amnion. Since allantois and amnion are non-innervated, the
      selective changes of the barriers and the drop of plasma amino acids must be
      mediated by so far unidentified humoral messengers.

PMID- 9773512
TI  - The acute phase response in the Sudan plated lizard, Gerrhosaurus major.
AB  - The Sudan plated lizard (Gerrhosaurus major), previously reported to be an
      afebrile species, was utilized in a series of experiments to test for various
      aspects of the acute phase response. Treatment of individuals with the antibiotic
      Baytril resulted in a slight (0.5 degree C) but significant reduction in mean
      selected body temperature (MSBT), while treatment with saline did not lower MSBT.
      Nonantibiotic treatment individuals had depressed plasma iron levels (86.6 +/-
      22.4 micrograms Fe 100 ml-1 plasma) and treatment with Baytril produced a
      significant increase in plasma iron concentration (186.8 +/- 19.5 micrograms Fe
      100 ml-1 plasma). Necropsy of randomly selected individuals indicated that
      animals obtained from the commercial supplier had Aeromonas, Arthrobacter,
      Pseudomonas and Salmonella infections and antibiotic treatment eliminated these
      infections. The growth rate of Aeromonas sobria is reduced when the bacteria are
      grown at 32 degrees C and reduced iron concentration compared to 34.5 degrees C
      and low iron concentration, which suggests that a fever response may not be
      beneficial in reducing bacterial growth. Saline injected, bacteria injected and
      antibiotic injected Gerrhosaurus major have high plasma zinc concentrations
      compared to the previously studied febrile species, Dipsosaurus dorsalis. This
      difference suggests that zinc concentrations in afebrile species deserve further
      study.

PMID- 9773514
TI  - California ground squirrel body temperature regulation patterns measured in the
      laboratory and in the natural environment.
AB  - Body temperature (Tb) was measured by telemetry in both laboratory maintained and
      natural environment California ground squirrels, Spermophilus beecheyi.
      Laboratory animals had a mean diurnal Tb of 37.5 degrees C under conditions of LD
      14:10, 20 degrees C and 36.5 degrees C under conditions of LD 10:14, 20 degrees C
      (P < 0.01). Nocturnal mean Tbs were 37.1 and 35.2 degrees C, respectively (P <
      0.05). Mean diurnal Tbs for each animal in the natural environment ranged from
      39.3 to 40.1 degrees C (mean = 39.6 degrees C) during both study seasons which
      included the hot season months of March through August and the cool season months
      of December through February. Natural environment hot season mean Tb was not
      significantly different from cool season mean Tb but both mean Tbs were
      significantly different from the diurnal mean Tbs measured in the laboratory (P <
      0.05). California ground squirrels exhibit an open-field stress induced
      hyperthermia in the laboratory which can be extended for periods up to 6 h. The
      hyperthermic response is blocked by L-propranolol at a dosage of 15 mg kg-1.
      Laboratory animals do not habituate to repeated open-field exposures over a five
      consecutive day period. It is suggested that stress hyperthermia might be a
      normal component of thermoregulation in some free-living ground squirrels because
      of the openness of the habitat in which they exist.

PMID- 9773513
TI  - Acetylcholine is a vasodilator of porcine skeletal muscle arteries.
AB  - The purpose of this study was to test the hypothesis that porcine skeletal muscle
      arteries exhibit concentration-dependent vasodilation in response to
      acetylcholine (ACH) as observed in other mammals. We conducted three experiments.
      First, vasorelaxation responses to ACH were examined in isolated segments of
      femoral and brachial arteries, mounted on myographs and studied in vitro. Second,
      we determined whether resistance arteries from porcine skeletal muscle exhibit
      vasodilation in response to ACH by isolating second order arterioles (2-A) from
      the medial (MHT), deep-long (LOH) and lateral (LAT) heads of the triceps brachii
      muscles of four pigs. The rationale for selection of arterioles from these
      muscles was that these muscles represent muscles composed primarily of slow
      oxidative, fast-oxidative-glycolytic, and fast-glycolytic muscle fiber types,
      respectively. 2-As were isolated and cannulated with micropipettes and
      intraluminal pressure set at 60 cm H2O. In both sets of in vitro experiments, we
      determined responses to an endothelium-independent dilator, sodium nitroprusside
      (10(-10)-10(-4) M), and to endothelium-dependent agents ACH (10(-10)-10(-4) M),
      and bradykinin (BK; 10(-11)-10(-6) M). Third, we used transcutaneous ultrasound
      imaging to measure changes in artery diameters and Doppler-principle measurements
      of blood flow velocities to estimate changes in total blood flow in the femoral
      vascular bed. Results reveal that ACH and BK produced similar vasorelaxation
      responses in femoral and brachial arteries and vasodilation of skeletal muscle 2
      As. Also, ACH produced increases in blood flow and decreases in vascular
      resistance in the femoral vascular bed. These results indicate that the arterial
      tree of porcine skeletal muscle exhibits ACH-induced, endothelium-dependent
      vasodilation.

PMID- 9773515
TI  - Rank dependent seasonal levels of IGF-1, cortisol and reproductive hormones in
      male pudu (Pudu puda).
AB  - We tested the following hypothesis: when two pudu males share a single pen
      throughout the year, the dominant animal will have a higher level of IGF-1 than
      its subordinate pen mate, particularly during the period of increased social
      friction (e.g. rut and establishment of territories). To test this hypothesis, we
      used data from six adult males maintained at the University of Concepion, Chile
      (latitude 36.6 degrees S), and analysed them from the males' dominance point of
      view. Two males plus eight to ten females were kept in one pen and although we
      did not specifically measure dominance, the rank position was obvious from
      frequent encounters between the bucks. Three consecutive blood samples were taken
      monthly over the period of 1 year. In addition to IGF-1, we also analysed
      seasonal levels of testosterone, cortisol, prolactin, LH and FSH. The analysis
      revealed that IGF-1 levels of dominant males were significantly higher than those
      of subordinate males from September to November (the second part of the antler
      growing period and time of establishing territories). Testosterone levels were
      higher and FSH levels were lower in dominant males during the rut. Levels of
      prolactin were higher in dominant animals in November (summer). Cortisol and LH
      did not show any significant differences between dominant and subordinate males.
      This data provides the first evidence indicating the possible link between
      dominance and blood levels of IGF-1. The functional explanation of such links is
      discussed.

PMID- 9773516
TI  - Effect of spermine administration on pancreatic maturation in unweaned rats.
AB  - The effect of oral administration of spermine on pancreatic maturation was
      investigated in the suckling rat. The treatment consisted of 0.3-0.4 mmol
      spermine kg-1 body weight given orally once a day for 3 days starting at day 11
      after birth. Spermine administration does not adversely affect the growth of the
      pancreas (wet weight, protein and DNA contents remain unchanged). The
      proliferating cell nuclear antigen (PCNA) index decreases significantly in
      spermine-treated rats, indicating that spermine slows down the proliferation rate
      of the organ. The enzymatic activities of trypsin, chymotrypsin and alpha-amylase
      are increased significantly in the pancreas of spermine-treated rats. The
      morphology of the organ seems affected as shown by hematoxylin-eosin staining: a
      cytoplasm indicative of higher synthetic activity is visible after spermine
      treatment. We conclude that spermine treatment of unweaned rats can induce
      precocious biochemical and morphological maturation of the exocrine pancreas,
      pushing the organ forward in the process of differentiation (closer to the adult
      stage).

PMID- 9773517
TI  - Cross immunity and vaccination against multiple microparasite strains.
AB  - We explore the equilibrium properties of a series of compartmental, ODE models
      describing the interaction between different strains of pathogen. The interaction
      is conceptualized as acting through shared antigens: infection and recovery from
      one strain leaves the host with a primed immune response against subsequent
      strains. The models consider the effect of this priming on susceptibility (the
      ability to be infected) and transmission (the ability to infect) in an SIR model.
      In these models, the specific past history of infection is encapsulated in
      different susceptible compartments within the model. In a third, SIS, model,
      specific past history is not included, but strains have differential abilities to
      infect previously infected hosts. Equilibrium results include criteria for the
      coexistence of strains. For the SIR models, the region of coexistence defined by
      parameters shrinks as the effect of strains on each other (increased antigenic
      similarity) increases. For the SIS model, coexistence depends critically on the
      rate at which complete susceptibility is recovered following infection, and
      coexisting strains must have differential abilities to infect completely and
      partially susceptible hosts. Interestingly, this model provides analogies to
      commensalism (the first species gains from the presence of the second; the second
      neither gains nor loses from the interaction) and symbiosis (the presence of both
      species benefits the other). Additionally, we show that the maximum number of
      coexisting strains is two in this model. The effect of vaccination depends on the
      initial strain structure, the ability of vaccination to mount protection to both
      strains and the coverage. Vaccination may allow a previously excluded strain to
      coexist or exist alone, and may allow a previously rarer strain to become more
      common with the possibility of increasing incidence of disease. We discuss the
      dynamics of these models, compare model results to observed patterns and consider
      additional model structures. The importance of these results to specific multi
      strain pathogens, in particular rotavirus, is considered.

PMID- 9773518
TI  - The effect of chemotaxis and chemokinesis on leukocyte locomotion: a new
      interpretation of experimental results.
AB  - A mathematical model is developed to describe the motion of leukocytes through a
      Boyden chamber. The model is based on the Keller-Segel model of cell motion and
      comprises three partial differential equations which describe the evolution of
      the neutrophils, the chemoattractant, and a neutrophil-derived chemokinetic
      factor. Where other authors have concentrated on chemotaxis, here attention is
      focused on the manner in which the chemokinetic factor influences neutrophil
      locomotion. Numerical simulations show how the number of neutrophils initially
      placed on top of the chamber affects cellular motion through the system and
      reproduce the qualitative behaviour observed by Takeuchi & Persellin (Am. J.
      Physiol. 236, C22-C29). In particular, the simulations show how dense packing of
      the neutrophils increases the levels of the chemokinetic factor. This enhances
      random cell motion and increases the speed with which the neutrophils reach the
      source of chemoattractant. For a particular asymptotic limit of the system
      parameters, the model reduces to a nonlinear partial differential equation for
      the neutrophils. Similarity solutions of this caricature model yield algebraic
      expressions relating the speed with which the neutrophil front penetrates into
      the chamber to the number of neutrophils initially placed on top of it. The
      implications of the results are also discussed.

PMID- 9773519
TI  - Numerical techniques and mathematical modelling for CI857-controlled gene
      expression and cell growth in recombinant E. coli.
AB  - Recombinant gene expression, monitored by beta-galactosidase activity, is studied
      in a pL, pR-CI857 plasmid expression system in temperature-induced E. coli batch
      cultures. The experimental procedure has been mathematically modelled, and the
      corresponding parameters are estimated from specific statistical and numerical
      methods, basically by using a global least-squares procedure under some
      constraints induced by the model. The numerical techniques proposed in this work
      act by accumulation of data coming from several runs of the modelled experiment,
      so that more accuracy is obtained in the parameter estimation. In particular, for
      the production process, an extra-model parameter depending on an indicator vector
      is introduced for each run of the experiment in order to globalize the data. The
      analysis of the data obtained leads to an integrated model for both cell growth
      and gene expression, which describes an asymmetric dynamics between culture
      growth and recombinant protein yield, and can serve to predict the maximal value
      of accumulated gene expression and the time required for it to be achieved at any
      age of the preinducing cell growth.

PMID- 9773520
TI  - Binomial cokriging for estimating and mapping the risk of childhood cancer.
AB  - The incidences of human diseases vary from place to place, and this is also
      likely to be so for the risk of people developing many of them. We have analysed
      the spatial distribution of childhood cancer in the West Midland Health Authority
      Region of England from 1980 to 1984. This is a rare disease which is considered
      to be noncontagious. The observed frequencies of the disease in the electoral
      wards have been converted to proportions that estimate the risk of a child's
      developing it. The spatial autocorrelation of the risk, expressed in the
      variogram, was determined in a novel way from the proportions within electoral
      wards by treating them as binomial variables dependent on the risk and the
      numbers of children in the wards. The observed variogram was modelled by
      Whittle's elementary two-dimensional correlation. Covariances of the proportion
      and cross covariances between the proportion and the risk were derived, and from
      the latter and the proportions the risk was estimated in two ways by a form of
      cokriging: ordinary and conditional unbiased cokriging. The variogram of the risk
      shows strong autocorrelation, and the kriged estimates, when mapped, have a
      distribution that is far from even. There are patches where the estimated risk is
      large, especially in the rural south west and the suburban north east; and there
      are other patches, notably the more densely populated areas, where it is small.

PMID- 9773522
TI  - Investigation of suramin-albumin binding by electrospray mass spectrometry.
AB  - Suramin, an organic polyanion with six sulphonic groups, is under clinical trials
      as an agent against hormone-refractory prostate cancer. The drug binds strongly
      to serum albumin. The objectives were to use electrospray to measure the
      molecular masses of the intact complexes of albumin and suramin to determine the
      number of suramin molecules bound under different molar ratios, and to
      investigate the binding of suramin in human serum. With albumin in excess (2:1 to
      25:1 ratio), only 1 and 2 bound suramins were found; with suramin excess (2:1 to
      1000:1) up to 20 bound suramin molecules/albumin were found. Up to 5 bound
      suramins were found in human serum with 4:1 suramin:albumin ratio, which
      corresponds to recommended therapeutic doses (200-300 micrograms/mL). At 8:1
      ratio, which would be toxic, complexes with up to ten bound suramin molecules
      were found, and unreacted albumin diminished.

PMID- 9773521
TI  - Preliminary evaluation of an SF5+ polyatomic primary ion beam for analysis of
      organic thin films by secondary ion mass spectrometry.
AB  - Organic vapor deposited thin films of pure biomolecules, polymer films and
      biomolecules dispersed in gelatin and biological tissue have been analyzed in a
      magnetic sector secondary ion mass spectrometer using an SF5+ primary ion beam at
      keV impact energies. In comparison to Ar+ bombardment under identical conditions,
      bombardment with SF5+ gives a 10 to 50 fold enhancement in the secondary ion
      yields for characteristic molecular ions. The SF5+ primary ion beam can be
      focussed to a small spot allowing molecular ion images to be obtained at
      micrometer spatial resolution with enhanced sensitivity. More importantly, the
      decay in molecular ion signal as a function of primary ion dose commonly observed
      in SIMS using monoatomic primary ions is either eliminated or greatly reduced,
      allowing molecular depth profiles to be obtained of organic thin films. By
      continuing to sample intact molecules as sputtering proceeds into the sample, the
      total number of detected characteristic secondary ions is increased by as much as
      a factor of approximately 700 for SF5+ bombardment as compared to Ar+ bombardment
      under identical analytical conditions. This effect is thought to be a result of
      the high erosion rate and the low penetration depth inherent in the use of a
      polyatomic primary projectile.

PMID- 9773523
TI  - Differentiation of lysine/glutamine in peptide sequence analysis by electrospray
      ionization sequential mass spectrometry coupled with a quadrupole ion trap.
AB  - Electrospray ionization coupled to a quadrupole ion trap mass spectrometer is
      used to differentiate between the isobaric amino acids lysine and glutamine in
      sequence analysis of peptides. Collision-induced dissociation is used for
      fragmentation. Several isobaric peptides with one or more lysines or glutamines
      at different positions were investigated. The ambiguous amino acid either in the
      peptide chain or at the C- or N-terminus can be clearly identified based on
      specific side chain fragment ions resulting from MS3 or MS4 of B- and Y"-fragment
      ions.

PMID- 9773525
TI  - Study of mechanisms involved in the collision-induced dissociation of carboxylate
      anions from glycerophospholipids using negative ion electrospray tandem
      quadrupole mass spectrometry.
AB  - The collision-induced dissociation of the carboxylate anions from human blood
      phosphatdilycholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS),
      phosphatidylinositol (PI) and phosphatidic acid (PA) containing the C18:0 (sn-1)
      and C20:4 (sn-2) fatty acyl residues was studied using normal phase liquid
      chromatography coupled with negative ion electrospray tandem mass spectrometry.
      The product ion peak area ratio of C18:0 to C20:4 was calculated for each
      phospholipid species and was found to increase with increasing collision energy
      for all classes. For the phospholipids with a net neutral charge (PE, PC) there
      was a preferential loss of the sn-2 carboxylate anion (C20:4) at low collision
      energy, while at higher energy there was a preferential loss of the sn-1
      carboxylate anion (C18:0). For the phospholipids with a net negative charge (PI,
      PA, PS) the intensity of the sn-1 carboxylate anion peak was equal to or higher
      than the sn-2 carboxylate anion peak at the energies measured. At a given
      collision energy the product ion peak area ratio decreased in the order PA > or =
      PS > PI. Studying PS and PE species at different collision energies, it was found
      that for both classes the increase in the abundance ratio with increasing
      collision energy was largely dependent on the chain length and degree of
      unsaturation of the sn-2 acyl chain.

PMID- 9773524
TI  - The use of high-flow high performance liquid chromatography coupled with positive
      and negative ion electrospray tandem mass spectrometry for quantitative
      bioanalysis via direct injection of the plasma/serum samples.
AB  - Two bioanalytical methods have been developed and validated utilizing high flow
      high performance liquid chromatography (HPLC) for on-line purification of plasma
      and serum samples and electrospray tandem mass spectrometry for detection and
      quantitation. Each plasma or serum sample, after mixing with an aqueous solution
      of the internal standard, was injected into a small diameter (1 x 50 mm) column
      packed with large particles of OASIS (30 microns), with a 100% aqueous mobile
      phase at a high flow rate (3-4 mL/min). The combination of the high linear speed
      (6-8 cm/s) of the aqueous mobile phase and the large particle size resulted in
      the rapid passage of the proteins and other large biomolecules through the column
      while the small-molecule analytes were retained on the column. During this
      purification period, the HPLC effluent was directed to waste. After the
      purification step, the HPLC mobile phase was rapidly changed from 100% aqueous to
      < or = 100% organic, the flow was reduced to 0.5-0.8 mL/min, and the column
      effluent was directed towards the mass spectrometer. The small molecule analytes
      were eluted during this period. In the method developed and validated for the
      quantitative determination of compound I in rat plasma (method A), the same OASIS
      column (1 x 50 mm, 30 microns) served as the purification and analytical
      (elution) column. In the method developed for the simultaneous determination of
      pravastatin and its positional isomer biotransformation product (SQ-31906) in
      human serum (method B), the purification column was connected to a conventional
      C18 analytical column (3.9 x 50 mm, 5 microns) to achieve the required
      chromatographic separation between the two isomers. For method A, where 50 microL
      of rat plasma mixed 1:1 with water containing the internal standard was injected,
      the standard curve range was 1 to 1,000 ng/mL. For method B, where 200 microL of
      a human serum sample mixed 4:1 with water containing the internal standard was
      injected, the standard curve range was 0.5 to 100 ng/mL. The total analysis time
      for each method was < or = 5 min per sample. The accuracy, inter-day precision
      and intra-day precision were within 10% for both methods.

PMID- 9773526
TI  - Determination of n-hexane metabolites by liquid chromatography/mass spectrometry.
      1. 2,5-hexanedione and other phase I metabolites in untreated and hydrolyzed
      urine samples by atmospheric pressure chemical ionization.
AB  - The capabilities of atmospheric pressure chemical ionization liquid
      chromatography/mass spectrometry (APCI-LC/MS) were investigated for the analysis
      of urinary 2,5-hexanedione (2,5-HD) and for the identification and
      characterization of other n-hexane Phase I metabolites in hydrolized urine
      samples. Chromatography was performed under reversed phase conditions at 0.75 mL
      min-1 flow rate. The ionization of 2,5-HD and other n-hexane metabolites was
      obtained in positive ion mode. After optimization of several interface
      parameters, the linearity, sensitivity and precision of the method were
      determined operating in the selected ion monitoring mode. Detection limits were
      0.02 and 0.05 mg L-1 in water and urine respectively, with linear calibration
      curves in the 0.05-10 L-1 concentration range. Repeatability and both intra-day
      and inter-day precision were determined at two concentration levels (0.5 and 5.0
      mg L-1), and relative standard deviations were in the 1.3%-5.3% range. The method
      was applied to the quantitative analysis of 2,5-HD in urine samples from an
      external Quality Assurance Programme for Organic Solvent Metabolites. Moreover,
      the metabolites 5-hydroxy-2-hexanone, 2,5-hexanediol and 4,5-dihydroxy-2-hexanone
      were identified and confirmed in hydrolyzed urine of rats exposed to n-hexane.

PMID- 9773527
TI  - The effect of hydroxypropyl-beta-cyclodextrin on the kinetics of hydrolysis of an
      oxazolidine prodrug.

PMID- 9773528
TI  - [Research in education programs].
AB  - Postgraduate medical training is intended to give competence in a specific field
      of medicine. Postgraduate programs should therefore be designed to offer the
      appropriate opportunities for the acquisition of specific knowledge and skills
      required for expertise in that particular medical or surgical specialty. The
      trained physician should not only be able to practice his specialty, but also
      have a deep understanding of the fundamental knowledge involved and convey this
      experience to others. Scientific curiosity, critical reasoning, persistence, and
      the ability to work in a team are important qualities that should be developed
      during post graduate training. Due to its requirements and methods, research
      clearly emerges as an important tool in promoting the timely achievement of these
      main objectives. All departments should be involved in basic or clinical
      research, and this work should be part of the postgraduate program. Finally,
      research activities should be appropriately valorized in the overall appreciation
      of the trainee's curriculum.

PMID- 9773529
TI  - [The skin allograft reduces the incidence of mammary cancer in Co60-irradiated
      female mice].
AB  - Skin allografts were performed in 51 BALB/c female mice by means of an easy
      technique devised by the authors. The skin for the allografts was taken from
      C57BL/6 male mice. All the mice were homozygotic. One month after the graft, the
      female mice were irradiated with 400 cGy of Co60. A control group of 148 female
      mice belonging to the same strain and with the same age were irradiated in equal
      conditions. All the animals were observed daily and all the occurrences
      registered. Dead animals were identified and their necropsies performed. Results
      were analysed bearing in mind the incidence of malignancy. It was observed that
      mammary carcinoma was the most frequent solid tumour and that the statistical
      difference between mice with skin allografts and those of the control group was
      significant (p = 0.009). In the two groups studied the difference between dead
      animals without tumour pathology was also statistically significant (p = 0.0011).
      With regard to other neoplastic pathologies, the results were not statistically
      different between the two groups of animals. According to the literature, skin
      allografts have not been used in oncogenic protection. However, in this work,
      irradiated mice proved to be protected against oncogenic effects of Co60
      radiation, when they had previously received a skin graft. In conclusion, the
      authors emphasize the protection of skin allograft in BALB/c female mice against
      the oncogenic effect of Co60 radiation in the mice studied, with special
      significance for mammary carcinoma.

PMID- 9773530
TI  - [Skin cancer].
AB  - The authors, using the Cancer Registry data of S. Antonio General Hospital in
      Oporto, selected the cancer cases from 1981 to 1993. Distribution according to
      age, sex, topography and morphology is presented. Seven point nine percent of the
      12,124 cases mentioned in the Registry were skin cancers (n = 883). They were
      mostly on the face (56.8%), trunk (11.7%) and scalp and neck (7.7%). As for the
      type of tumour, 472 basaliomas, 231 squamous cell carcinomas and 63 melanomas
      were recorded. One may conclude that basaliomas and squamous cell cancers arise
      at a later age than melanomas; melanomas are more frequent on the lower limbs and
      on the trunk; squamous cell carcinomas are more frequent on the face and lips.
      Basalioma is more frequent on the face. These results are in accordance with
      those published internationally.

PMID- 9773532
TI  - [The role of external radiotherapy in the treatment of medullary carcinoma of the
      thyroid].
AB  - Medullary carcinoma of the thyroid represents 3 to 10% of all thyroid cancers.
      Surgery is the main treatment. External beam radiotherapy has a fundamental role
      in the treatment of residual disease following surgery, in cases of cervical node
      involvement, and in unresectable tumors. Between 1975 and 1993, 12 patients with
      medullary carcinoma of the thyroid were treated at the Department of Radiotherapy
      of the Portuguese Institute of Oncology in Oporto. Nine of these patients (75%)
      were male and 3 (25%) female, ranging from 24 to 80 years of age (mean = 43). All
      of them had residual tumor after surgery and underwent treatment with external
      beam radiotherapy. The follow-up period ranged from 36 to 180 months, with a
      median of 78 months; 8 patients (66.7%) are alive, 5 of them show no evidence of
      disease. Average survival was 70 months, and 4 patients (33%) died with
      metastatic disease. The aim of this paper is to analyse the role of external beam
      radiotherapy in local control of these tumors, with a brief review of the
      literature.

PMID- 9773531
TI  - [The solitary pulmonary nodule. A retrospective study of 119 cases].
AB  - The authors review 119 cases of solitary pulmonary nodule submitted to surgery,
      analysing their aetiology and correlating them with their clinical and
      radiological aspects as well as with the patient's age, sex and smoking habits.
      An analysis of some pre-surgical diagnostic methods was also made. In half of the
      nodules (54%) the diagnosis made was of malignancy. Some of these (8%) were
      pulmonary metastases. There was no sex preference in the distribution of
      malignant or benign lesions. The average diameter of malignant nodules was 2.8 +/
      10.9 cm and benign nodules 2.1 +/- 10.9 cm. The large majority of malignant
      lesions was found in both upper lobes, whilst benign lesions did not have a
      preferential location. Adenocarcinomas were the most common primary lung tumours
      found, (59%), followed by squamous (27%) and neuroendocrine tumours (12.5%). Most
      benign nodules were benign neoplasias (43%--hamartomatous tumours) or of
      infectious aetiology (mostly granulomatous chronic disease--39%). The evaluation
      of the imagiological criteria of benignity or malignancy resulted in a
      sensitivity of 67% and specificity of 76%. In this study, negative respiratory
      cytology and bronchofibroscopic biopsies were not particularly helpful in
      excluding malignancy. This study confirms results published by other authors, in
      concluding that larger nodules have a greater probability of malignancy, that
      these are more frequent in males with smoking habits, and that they predominate
      in the upper lobes.

PMID- 9773533
TI  - [A correct and an augmented medical act].
AB  - The author describes a correct medical procedure and what may be called an
      augmented medical procedure. Reference is made to some of the formal and material
      conditions and bases of clinical deliberation. It is shown why one should reread
      Hippocrates, Aristotle and other physicians and philosophers who considered these
      issues. Thus the author reviews the principles and practices that made humanity
      and created clinical medicine. The casuistic model of the medical procedure is
      compared to the so-called model of medicine based on fact. This paper provides a
      clear position on the value and significance of individual responsibility.

PMID- 9773534
TI  - [A skin lymphoepithelial tumor (skin lymphadenoma)].
AB  - The study of a case of cutaneous lymphadenoma and a literature review allowed us
      to verify that, in contrast to immunohistochemical findings, clinical and
      histological dates are basically reproducible. Accordingly the eccrine or hair
      follicle natures of the pleonasm cannot be either excluded or confirmed. The
      initial terms "cutaneous lympho-epithelial tumor" or "epithelial
      lymphohistiocytic tumor" seem more suitable than that of "cutaneous lymphadenoma"
      to describe this peculiar skin neoplasm.

PMID- 9773535
TI  - [The Maffucci syndrome with axial bone lesions. A rare cause of low back pain].
AB  - The authors describe the case of a twenty-nine-year-old female with the diagnosis
      of Maffucci's syndrome, since the age of five, with lower back and lower limb
      pain. The diagnosis was made of bone axial lesions, which are seldom found in
      this syndrome. Sarcomatous transformation was found in one of them.

PMID- 9773536
TI  - [Giant-cell tumor of bone].
AB  - Giant-cell bone tumors are a rare entity. Only 7.5 to 15% are malignant tumors
      and correspond to 0.5% of all primary malignant bone tumors. This case report has
      an unusual localization (ischium) for this kind of tumor (+/- 0.6%). The patient
      was treated with radiotherapy alone, because local extension of the disease would
      require very aggressive surgery with functional implications. Ten years after
      treatment, the patient is alive without clinical evidence of disease, and without
      functional impairments.

PMID- 9773537
TI  - [Microangiopathic hemolytic anemia. A form of presentation of stomach neoplasm].
AB  - The authors report the case of a 53-year-old female with symptomatic anemia and
      hemorrhagic diathesis. The patient presented thrombocytopenia, microangiopathic
      hemolytic anemia and leukoerythroblastic reaction in peripheral blood film. The
      diagnosis of metastatic gastric carcinoma was made by subsequent studies. A
      review is made of the literature concerning microangiopathic hemolytic anemia,
      namely its etiology, mechanisms of pathogenesis and association with metastatic
      carcinoma.

PMID- 9773539
TI  - [Gastric adenocarcinoma and carcinoid].
AB  - The authors present a case report of synchronous gastric carcinoid and
      adenocarcinoma. The diagnosis of gastric carcinoid and its association with
      gastric carcinoma is discussed.

PMID- 9773538
TI  - [Gliosarcomas].
AB  - Gliosarcomas are rare tumors of the central nervous system with a poor prognosis.
      Histologically these tumors are characterized by an admixture of neoplastic glial
      cells and sarcomatous elements. Due to the scarcity of data in literature, the
      diagnosis is often missed and treatment is difficult. The authors report three
      cases of cerebral gliosarcomas and review the literature on this subject.

PMID- 9773541
TI  - [Peritoneal carcinomatosis].
AB  - Searching for the primitive tumor of a peritoneal carcinomatosis (PC) is no easy
      task even considering the multiple modern diagnostic procedures at our disposal.
      Without the primary site of a neoplasm it is often difficult to establish the
      prognosis and a treatment regimen. In PC the most frequent primitive tumors are
      ovarian neoplasms in women and gastrointestinal neoplasms in men. We present a
      case report of a 70-year-old Caucasian woman who was referred to our department
      for diagnosis and management of a PC. A fine-catheter aspiration cytology of the
      peritoneal implants was performed and provided histologic evidence of an ovarian
      papillary type carcinoma. This case is suggestive of what has been called in
      recent literature extraovarian peritoneal serous papillary carcinoma. Absent or
      insignificant histology of the ovaries of primary in-situ ovarian carcinoma is
      one diagnostic criterion. This patient had no evidence of ovarian disease
      considering ultrasound imaging and computer tomography. Unfortunately, since both
      laparotomy and laparoscopy were contraindicated, histology of the ovaries is
      lacking.

PMID- 9773542
TI  - [Bronchial fibroscopy in pediatric pulmonology].

PMID- 9773540
TI  - [Radiotherapy-induced pemphigus].
AB  - The authors report the clinical case of a woman exposed to ionizing radiotherapy,
      for the treatment of breast carcinoma, in whom a pemphigus lesion developed
      within the area of irradiation. This is, to the authors' knowledge, the 14th case
      of ionizing radiation-induced pemphigus.

PMID- 9773543
TI  - [Cytokines and bronchopulmonary dysplasia].

PMID- 9773545
TI  - [Intestinal permeability in the first year of life. The effect of diarrhea].
AB  - OBJECTIVE: The permeability of the intestinal mucosa to lactulose and mannitol
      was explored longitudinally in infants at 1, 3-4 and 11-12 months of age. This
      was also evaluated during the episodes of diarrhea that they suffered during
      follow-up. PATIENTS AND METHODS: Sugar excretion was measured by gas
      chromatography in five-hour urine samples. RESULTS: A decrease in lactulose
      excretion was observed, which became significant at 11-12 months of age (p =
      0.02). No changes were detected in mannitol excretion, although this showed a
      tendency to decrease. The lactulose/mannitol (L/M) ratio remained unchanged.
      During the 15 episodes of diarrhea observed in these infants during the 12 month
      follow-up, a considerable increase in this ratio was seen, due mainly to
      increased lactulose excretion. CONCLUSIONS: It is hypothesized that the decrease
      in lactulose excretion between one and 11-12 months of age is part of the
      maturational process of the intestinal barrier, while diarrhea results in
      increased permeability due to damage to the absorptive epithelium.

PMID- 9773544
TI  - [Association between lipid profile and Apo E genotype in Spanish children (8-15
      years old)].
AB  - OBJECTIVE: Different studies conclude that apoprotein E (Apo E) is a genetic
      determinant of lipid levels and cardiovascular risk, although these studies have
      been carried out principally in adults, with scarce and variable results
      available in children. The aim of our study was to analyze the association
      between lipid profile and the different Apo E isoforms (E2, E3 and E4) in a group
      of Spanish children. PATIENTS AND METHODS: In a transversal study, apo E
      genotypes and the lipid profile [total cholesterol (TC), LDL-c, HDL-c,
      triglycerides (TG), Apo A1, apo B and Lp(a)] were determined in 191 children (110
      boys and 81 girls) between 8 and 15 years of age. Apo E genotyping was performed
      by means of polymerase chain reaction and subsequent digestion with the
      restriction enzyme HhaI. RESULTS: The relative frequency for the E3, E4 and E2
      alleles were 0.87, 0.09 and 0.04, respectively. Total cholesterol, LDL-c and Apo
      B serum levels were highest in the group of individual with the genotypes E3/E4
      and lowest in the group E2/E3, while E3/E3 individuals had intermediate levels.
      When analyzed according to gender, we only found statistical significance in the
      group of girls (p < 0.004). CONCLUSIONS: The apo E genotype was significantly
      associated with lipid differences observed in the childhood population and this
      is modulated by gender.

PMID- 9773546
TI  - [Clinical and epidemiological analysis of 1,451 pediatric surgery consultations
      in a third level hospital referred from the primary health care sector].
AB  - OBJECTIVE: The aim of this study was to determine the pediatric surgery demands
      in a third level hospital due to referrals from the primary health care sector in
      order to better plan the work and continuing education programs. PATIENTS AND
      METHODS: The total number of patients (1,451) consulting a service of pediatric
      surgery for the first time and referred from the primary care sector during a
      twelve month period were studied. RESULTS: A total number of 1,451 children, with
      a maximum age of 14 years consulted. The assistential pressure was 22.01
      consultations/pediatrician/day in one year. Consultations by children older than
      7 years of age comprised 31.42% of the total. As for the distribution of these
      consultations, 61.26% were with a previous appointment, 38.74% were remitted to
      the second level. The most frequent reasons for consultations were inguinal
      hernia and hydrocele (30.46% of the cases), followed by phimosis (28.8%),
      undescended testis (8.2%) and skin neoplasms (5.78%). CONCLUSIONS: The demands of
      pediatric surgery consultations referred from the primary health care sector is
      very important. It is necessary to adapt the continuing education programs so
      that pediatric residents and primary medicine physicians are more aware of the
      surgical pathologies that are most frequently found in primary care centers and
      to decrease the assistential pressure of the pediatric surgery consultations in
      the hospital.

PMID- 9773547
TI  - [Fat distribution in children and adolescents of both sexes].
AB  - OBJECTIVE: The aim of this study was to describe anthropometric indexes of fat
      distribution in 6.0 to 14.9 year old children and to estimate the timing of
      differentiation of fat patterning in male and female children and adolescents.
      PATIENTS AND METHODS: We have studied a sample of 1,360 children (701 boys and
      659 girls) from Zaragoza, Spain. We have measured triceps and subscapular
      skinfold thicknessess and waist and hip circumferences. With these measurements,
      we have calculated the indexes of fat distribution including waist-to-hip
      circumference ratio and triceps-to-subscapular skinfold thickness ratio. We
      present the percentiles of these indexes. RESULTS: All percentiles of the waist
      to-hip ratio were higher in males than in females. Percentiles 5, 50 and 95 of
      the triceps-to-subscapular skinfold thickness ratio showed similar values in
      males and females, except that percentile 95 was higher in males than in females
      after 10.5 years. CONCLUSIONS: The waist-to-hip ratio seems to define earlier the
      pattern of fat distribution in children than does the triceps-to-subscapular
      skinfold thickness ratio. If we take into account the waist-to-hip ratio, the
      pattern of fat distribution is already present in school age children.

PMID- 9773548
TI  - [The value of lipid profile and of CT/C-HDL, C-LDL/C-HDl, Apo B/A indexes and
      atherogenic index in 6-year-old children from Rivas- Vaciamadrid].
AB  - OBJECTIVE: The purpose of this study was to analyze the lipid profiles in
      children six years of age according to sex and to compare this with other Spanish
      studies. PATIENTS AND METHODS: A transverse epidemiological study was performed.
      All six year old children in our area were studied. The following tests were
      performed in all children: total cholesterol (TC), triglycerides, LDL-C, HDL-C,
      apoproteins A and B after fasting for ten hours. In addition, TC/HDL-C, LDL-C/HDL
      C, and Apo B/A ratios and atherogenic index (ATI) were calculated. RESULTS: A
      population of 673 subjects (352 males and 321 females) were studied. The value of
      TC, triglycerides, LDL-C, Apo B, LDL-C/HDL-C and TC/HDL-C were significantly
      greater in females compared to males. Males had higher levels of HDL-C and ApoA.
      The values were similar to those obtain in Madrid in 1992, except that the values
      of HL-C were significantly higher in both sexes. CONCLUSIONS: In six year old
      children, the lipid profile in girls is worse than in boys. The data from our
      study do not show that the lipidic risk is getting worse during the past years in
      Spanish children.

PMID- 9773549
TI  - [Differences between morning and afternoon in the assessment of nutritional
      status by bioelectric impedance in children].
AB  - OBJECTIVE: The aim of this study was to examine if there were differences in the
      assessment of the nutritional status between values of bioelectric impedance (BI)
      measured in the morning (08:30) and in the afternoon (17:00). PATIENTS AND
      METHODS: We have studied 30 boys between 6.5 and 10.9 years of age. Weight,
      stature, skinfold thickness and total body impedance (Z) were measured at 08:30
      and at 17:00 on the same day. RESULTS: In 28 of 30 boys, Z at 17:00 was lower
      than Z at 08:30. The mean decrease in Z was 4.64% of the morning result (p =
      0.0001). At 17:00 there was an increase in total body water (TBW) and fat-free
      mass (FFM) measured by BI, 0.681, and 0.93 Kg, respectively (p = 0.0001),
      compared with morning values. We did not find differences between skinfold
      thickness values in the morning and in the afternoon, except for the suprailiac
      skinfold, which was a bit larger in the afternoon (p = 0.05). In the morning and
      afternoon there was a high correlation between FFM measured by skinfold thickness
      and values of TBW and FFM measured by BI. CONCLUSIONS: Z in boys decrease in the
      afternoon (17:00) compared with morning values (08:30). This fact must be
      considered by the pediatrician when IB is used for the assessment of nutritional
      status in children.

PMID- 9773550
TI  - [Central nervous system tumors in children less than three years of age].
AB  - OBJECTIVE: Central nervous system (CNS) tumors are the most frequent solid tumors
      in children. Twelve to twenty percent are diagnosed in patients younger than two
      years of age and these patient present more morbidity and mortality due to the
      illness and the treatment itself. PATIENTS AND METHODS: A retrospective study of
      CNS tumors in children younger than three years of age diagnosed in our hospital
      between 1985 and 1995 was carried out. RESULTS: We treated 21 patients between
      1985 and 1995. There were 10 male and 11 females. The mean age was 20.3 months
      (range: 0-32 months). The mean time between symptoms and treatment was 2.4 months
      (range: 0-18 months). The most common symptoms included ataxia, nausea and
      vomits. The most common locations of the tumor were: infratentorial (57.1%) and
      supratentorial (38.1%). Complete surgery was performed in 3 patients, subtotal in
      10, partial in 5, and a biopsy in 2. The anatomical-pathological diagnosis was:
      astrocytoma (6), ependinoma (5), meduloblastoma (4), ganglioglioma (1),
      neuroblastoma (1), and primitive neuroectodermic tumor (1). We could not document
      the histology in 3 patients. Ten patients received chemotherapy that was well
      tolerated and 14 received radiotherapy whose sequels were updated. The mean
      follow-up period was 44.42 months (range: 0-136 months). Overall survival was
      42.86%. There were no statistically significant differences in survival between
      those who were irradiated and those who were not, nor between those with supra-or
      infratentorial tumors. CONCLUSIONS: CNS tumors in children younger than three
      years of age have a worse prognosis than in older children. New therapeutic
      schedule with chemotherapy are being tested to avoid radiotherapy side-effects.

PMID- 9773551
TI  - [Neonatal screening for sickle cell disease in the Consorci Sanitari de Mataro.
      Rationale and first results].
AB  - OBJECTIVE: Neonatal screening for sickle cell disease in prevalent population
      permits its early detection and provides the possibility of starting early
      prophylactic measures that will greatly reduce the high mortality of the disease.
      METHODS: We expose the preliminary results of a neonatal screening for sickle
      cell disease, with alkaline and acid hemoglobin electrophoresis, selective for
      the black population coming from subsaharian Africa ad immigrated to our area.
      They are 82 black neonates born in our hospital between July 1995 and July 1997.
      RESULTS: Despite they are too few, we can talk about a gene prevalence (S, C) of
      10.98% (95% IC 4.21-17.74), and a disease prevalence (SS, CC, SC, S
      betathalassemia) of 1.22% (95% IC 0.00-3.60) which is slightly lower that what we
      expected. CONCLUSIONS: Neonatal screening for sickle cell disease in the black
      immigrated is necessary, and alkaline and acid hemoglobin electrophoresis is an
      appropriate technique.

PMID- 9773552
TI  - [Congenital chylothorax].
AB  - OBJECTIVE: The aim of this study was to study the prenatal diagnosis, clinical
      manifestations and karyotype results in congenital chylothorax. PATIENTS AND
      METHODS: A retrospective survey of a 20 year period was carried out. The prenatal
      diagnosis, maneuvers following delivery, malformations and clinical outcome were
      studied. RESULTS: We found 10 cases of congenital chylothorax. Four were
      diagnosed by prenatal ultrasound with pleural effusion and no other signs of
      hydrops and six were diagnosed postnatally. Of the later, five had respiratory
      distress and one was diagnosed by radiological procedures. In all 10 cases,
      postnatal thoracocentesis was performed for diagnosis and therapy, five infants
      required mechanical ventilation and four parenteral nutrition. One patient died
      72 hours after birth and three within 24 hours of birth. The clinical outcome of
      the rest was successful and were placed on a medium-chain triglyceride formula
      that was given orally. Of the eight karyotypes studied, six trisomy 21 were
      found. CONCLUSIONS: The prenatal diagnosis of pleural effusion permits prompt
      recognition of congenital chylothorax and allow for appropriate treatment upon
      birth. Medical therapy including pleural drainage and total parenteral nutrition
      and medium-chain triglyceride formula for oral feedings is successful in the
      majority of cases. Down's syndrome should be considered in fetuses or newborns
      with pleural effusion.

PMID- 9773553
TI  - [Microscopic polyangiitis: a case report].

PMID- 9773554
TI  - [Pulmonary balloon dilatation and simultaneous ductus closure].

PMID- 9773555
TI  - [Bronchial carcinoid tumor: a case report].

PMID- 9773556
TI  - [Metatrophic dysplasia: a case report, etiological considerations and
      prevalence].

PMID- 9773557
TI  - [Recurrent torticollis due to cervical osteochondroma. Case report and review of
      the literature].

PMID- 9773558
TI  - [Silent ductus arteriosus].

PMID- 9773559
TI  - [Infectious endocarditis in a child with pulmonary atresia and ventricular septal
      defect corrected by a valve conduit].

PMID- 9773560
TI  - [Necrotizing enterocolitis in the postop period of cardiac surgery in the
      neonatal period].

PMID- 9773561
TI  - [Idiopathic peri-intraventricular hemorrhage in the term infant].

PMID- 9773562
TI  - [Fever of unknown origin].

PMID- 9773563
TI  - [Acute pain, analgesia and sedation in children (V): analgesia and sedation in
      pediatric intensive care].

PMID- 9773565
TI  - [Treatment of meningococcal meningitis].

PMID- 9773564
TI  - [Elective treatment in meningitis caused by Neisseria meningitidis].

PMID- 9773566
TI  - [Elective treatment in meningitis due to Neisseria meningitidis].

PMID- 9773567
TI  - [Possible intoxication by taxine: a report of 2 cases].

PMID- 9773568
TI  - [The use of new vaccines by a pediatrician on an individual basis].

PMID- 9773569
TI  - [Continuous insulin perfusion in preterm infants with weight less than 1,500
      grams who receive parenteral nutrition].

PMID- 9773570
TI  - [Inhaled corticoids: are we sure they are safe?].

PMID- 9773571
TI  - [The examination of palatine tonsils in children and adolescents].

PMID- 9773572
TI  - [Idiopathic CD4+ lymphocytopenia: a clinico-immunological syndrome of uncertain
      significance].

PMID- 9773573
TI  - [The prognostic indices of cancer mortality in the elderly].
AB  - Although cardiovascular disease is still the main cause of mortality and
      morbidity in the elderly, numerous epidemiological studies have disclosed an
      increased incidence of neoplastic disease in this age group over the past few
      years. A population of 3282 > or = 65-year-old subjects taking part in the
      Cardiovascular Study in the Elderly was monitored to discern whether a number of
      variables, already recognized as predictive factors of overall and cardiovascular
      mortality, could also affect neoplastic mortality. Apart from age, which was the
      chief risk factor for neoplastic mortality, sex, cigarette smoking, the presence
      of respiratory symptoms and the blood levels of some enzymes were predictors of
      cancer mortality. These results must nevertheless be regarded with caution as a
      number of non-neoplastic diseases typical of the elderly may mimic the signs and
      symptoms of cancer.

PMID- 9773574
TI  - [The epidemiology and management of an acute asthmatic attack].
AB  - The mortality rate for acute asthma increased approximately 40% between 1982 and
      1991 in the United States, while hospital admissions remained constant. In order
      to verify if inadequate therapy at home could increase hospitalization for this
      pathology, we evaluated retrospectively 94 subjects admitted to the Emergency
      Department of Rho Hospital, near Milan (Italy), for acute asthma in 1996. We
      studied the correlations between some epidemiological variables (sex and age) and
      the hospitalization of asthmatic patients and described the different therapeutic
      approaches at home and in the Emergency Department. Our data show that subjects >
      40 years old, mostly females, were admitted more frequently than younger patients
      (38%) (p < 0.03). In comparison with the international guidelines we document the
      underuse of inhaled corticosteroids (69.7%) previous to the acute attack (p <
      0.01). In conclusion, we believe that the correct early use of inhaled
      corticosteroids at home could prevent hospitalization for asthma, particularly in
      the elderly.

PMID- 9773575
TI  - [Food habits and cardiovascular risk factors in 2 population samples of western
      Sicily].
AB  - Two population samples in western Sicily, one rural and one urban, were studied
      to evaluate the influence of dietary habits on cardiovascular risk factors. One
      hundred and fifty-five rural subjects (73 males, 82 females) and 155 age- and sex
      matched urban subjects (71 males, 84 females) were enrolled. All subjects related
      their personal and familial history, physical activity levels, and had a complete
      physical and instrumental examination. Blood was collected after an overnight
      fast, without stasis. The following parameters were measured: blood glucose,
      total cholesterol, HDL-cholesterol, triglycerides, apolipoproteins A1 and B100,
      fibrinogen, factors VII and VIII, tissue plasminogen activator, plasminogen
      activator inhibitor, and plasminogen. Dietary habits were recorded on two
      occasions by means of a week diary (7-day food record). The rural sample followed
      the so-called "Mediterranean diet", while the urban sample followed a diet with
      significantly higher cholesterol and fat (in particular saturated fatty acids)
      intake and a significantly lower fiber intake. Both males and females in the
      rural population had significantly lower total cholesterol and apolipoprotein
      B100 levels than those in the urban sample, although rural males had
      significantly higher HDL-cholesterol levels. Both males and females in the rural
      sample had significantly lower factor VII and plasminogen activator inhibitor
      levels, although rural males had lower tissue plasminogen activator and
      fibrinogen levels than their urban counterparts. The positive effects of the
      "Mediterranean diet" on lipid, coagulation and fibrinolytic parameters which play
      a key role in the pathogenesis of atherosclerosis indicate that this dietary
      pattern should be adopted by the entire population.

PMID- 9773576
TI  - [Sympathetic nervous factors, pressure variability and organ damage in arterial
      hypertension].
AB  - Animal models have shown that hypertension may be accompanied by an increase in
      sympathetic activity. The findings of increased plasma norepinephrine or
      increased muscle sympathetic nerve traffic have now provided clear evidence,
      however, that sympathetic activity is increased in essential hypertension and
      that adrenergic neural mechanisms are already involved in the early phase of this
      condition. Furthermore, in the early and late phases of hypertension, the
      presence of other cardiovascular risk factors frequently accompanying
      hypertension such as obesity, insulin-resistance, and smoking, concomitant with
      hypertension, brings about sympathetic activation which may be superimposed on
      the activation resulting from the hypertensive state itself. Finally, sympathetic
      activation is directly involved in the progression of end-organ damage and plays
      a paramount role in the cardiovascular structural changes typical of the blood
      pressure elevation occurring in left ventricular hypertrophy, arteriolar
      remodeling, and atherosclerosis. These findings underscore the importance of
      aiming anti-hypertensive treatment at the reduction not only of blood pressure
      levels, but also of enhanced sympathetic cardiovascular drive.

PMID- 9773577
TI  - [Lipid metabolic disorders in obesity: their epidemiology, physiopathology and
      clinico-therapeutic implications].
AB  - The centralization of body fat, particularly in abdominal or visceral depots, is
      associated with qualitative and quantitative lipid abnormalities. Examples of
      these qualitative alterations include changes in low density lipoprotein
      composition, namely an increased number of small or dense low density lipoprotein
      particles, which seem to be prone to increased lipid oxidation. Oxidative
      modification of low density lipoproteins is involved in atherosclerotic
      development of the arterial wall. Alterations of lipid composition often arise in
      a context of insulin resistance with hyperinsulinism. Genetic features, such as
      apolipoprotein E polymorphism, also play a significant role in lipoprotein
      metabolism. The principle treatment of obesity and associated dyslipidemia is to
      reduce energy intake through diet. Moderate exercise is effective, especially in
      patients with insulin resistance. Drug therapy is considered primarily for
      patients who refuse to make behavioral changes.

PMID- 9773578
TI  - Macroamylasemia in a man from Bangladesh. A case report.
AB  - A 30-year-old man from Bangladesh was admitted to the hospital because of
      abdominal pain. Elevated amylase values (both pancreatic and non-pancreatic
      fractions) indicated a diagnosis of acute pancreatitis although all tests
      conducted to confirm this were negative. Amylase isoenzyme electrophoresis
      disclosed an immunocomplex made up of a salivary amylase molecule with an IgA
      that increased total and pancreatic fractions. A diagnosis of macroamylasemia was
      made. Although this is considered to be a benign condition, it is generally
      identified only after a long series of tests which could be avoided by the use of
      simple amylase isoenzyme electrophoresis.

PMID- 9773579
TI  - [Idiopathic CD4+ T-lymphocyte deficiency: the clinical evolution of a case].
AB  - The case of a patient with Salmonella arizonae sepsis, esophageal candidiasis,
      and a low CD4+ T lymphocyte count is presented. Follow-up continued for over 2
      years after the patient was discharged from the hospital, and his clinical course
      and clinical-immunological examinations are described. After a period of several
      years during which the patient had recurrent acute infectious episodes, he
      improved markedly after cholecystectomy and toilette of the gingival inlets for
      severe parodontopathy. His CD4+ T cell count increased although it remained below
      normal values. This case points to possible hypothesis that chronic infective
      foci may further compromise the immune system when a congenital functional or
      numerical CD4+ T cell deficit is present.

PMID- 9773580
TI  - Bioethics in the medical subspecialty literature.
AB  - We have previously reported that a smaller percentage of the surgical literature
      than the medical literature is devoted to bioethics, and that this difference is
      statistically significant. In order to determine: 1) whether the medical
      subspecialty literature is more akin, in terms of its quantitative bioethics
      content, to the surgical or to the medical literature, and 2) whether differences
      exist between the "invasive" and the "noninvasive" medical subspecialties in
      terms of their quantitative bioethics content, we conducted a computerized search
      of the MEDLINE database. The journals searched were selected from the "Medicine",
      "Surgery", and "Cardiovascular System" sections of the "Brandon-Hill List", and
      the search was limited to the 1994 issues of these journals. From the 15 medical
      journals searched, 331 out of a total of 10,578 bibliographic records indexed
      dealt with bioethics, while from the 12 surgical journals searched only 14 out of
      a total of 3990 bibliographic records indexed dealt with bioethics. From the 26
      medical subspecialty journals searched (14 "invasive" and 12 "noninvasive"), 38
      (20 "invasive", 18 "noninvasive") out of a total of 12,733 bibliographic records
      indexed (5745 in the "invasive" literature, 6988 in the "non-invasive"
      literature) dealt with bioethics. We conclude that there is a statistically
      significant difference (p < 0.001) between the general medical literature and the
      medical subspecialty literature in terms of their quantitative bioethics content,
      that there is no such difference between the surgical literature and the medical
      subspecialty literature, and that no statistically significant difference exists
      between the "invasive" and the "noninvasive" medical subspecialties in terms of
      their quantitative bioethics content.

PMID- 9773581
TI  - [Bladder exstrophy].
AB  - OBJECTIVE: To describe the procedures of bladder exstrophy closure, epispadias
      repair to achieve urinary control. The approaches to the failed exstrophy are
      also described. METHODS: Bladder closure soon after birth is performed with
      concomitant pelvic osteotomy. The different techniques are described. The
      Cantwell-Ransley technique is preferred for epispadias repair and the Young-Dees
      Leadbetter procedure for bladder neck reconstruction. RESULTS: A success rate of
      92% and a failure rate of 31% have been reported by different authors.
      CONCLUSION: To date there is no definitive solution in the treatment of bladder
      exstrophy. Continent urinary diversion may be warranted in some cases.

PMID- 9773582
TI  - [Vaginal reconstruction in girls and young adults].
AB  - OBJECTIVE: There are many different approaches to vaginal reconstruction. Methods
      include simple dilatation, skin grafts techniques, amnion grafts and the use of
      bowel segments for vaginal replacement. METHOD: We herein discuss the most common
      surgical techniques and present our series of 15 patients who underwent
      intestinal vaginoplasty with either sigmoid colon or cecum. RESULTS: The
      complication rate was low, with two patients requiring revision for prolapse. Ten
      patients are sexually active with only one describing any degree of dyspareunia.
      CONCLUSION: When dealing with vaginal aplasia, intestinal vaginoplasty seems to
      have clear advantages with an excellent surgical success rate and low incidence
      of complications.

PMID- 9773583
TI  - [The surgical treatment of distal hypospadias].
AB  - Distal hypospadias is one of the most common conditions encountered by the
      pediatric urologist. For many years it was considered to be a non-surgical
      pathology, since attempts to correct this condition was cosmetically
      unsatisfactory and more problems were caused rather than resolved. Over the last
      15 years, early in the 80's, John Duckett rekindled the interest in this
      pathology whose treatment had advanced very little since the era of Mathieu. This
      article is a posthumous tribute to my mentor, John W. Duckett, who contributed
      considerably to the advancement of surgical treatment of hypospadias.

PMID- 9773584
TI  - [Proximal hypospadias].
AB  - OBJECTIVE: To evaluate the outcome of surgery in posterior hypospadias. METHOD:
      The technique of preservation of the urethral plate is described following three
      main steps: 1.-The first step is the correction of chordee which is mainly
      related to the two fibrous and vascular pillars sitting on each side of the
      urethral plate and representing the division of the atretic corpus spongiosum.
      Tethering of the urethral plate onto the anterior surface of the corpora
      cavernosa is another common cause of chordee which can be relieved by untethering
      the urethral plate from the ectopic meatus up to the glans cap. The urethral
      plate can be preserved in most cases of posterior hypospadias (35/43) and dorsal
      plication of the corpora cavernosa is rarely needed. 2.- The second step of this
      surgery is urethroplasty, which is usually achieved by using a pediculized
      preputial patch stitched to the urethral plate (onlay urethroplasty). 3.- Penile
      cover using the skin sleeve technique completes the procedure. RESULTS: Twenty
      one per cent fistulae, 1 meatal stenosis, no proximal stenosis are reported and
      discussed. CONCLUSION: Preservation of the urethral plate is possible in most
      posterior hypospadias and permits an onlay urethroplasty which remains to date
      the most reliable procedure to reconstruct the urethra in posterior hypospadias.

PMID- 9773585
TI  - [The treatment of hypospadias complexes].
AB  - OBJECTIVES: To explain the preoperative assessment of the hypospadias cripple and
      define the fundamental principles of correction of the failed hypospadias repair.
      METHODS: Through case presentation and literature review, the defects associated
      with the failed hypospadias repair including persistent chordee, urethral
      stricture, urethrocutaneous fistula, urethral diverticulum, meatal retraction and
      stenosis, failed glansplasty are elaborated. Decision-making points in selecting
      a method of repair are also provided. RESULTS: The principles of successful
      reoperative hypospadias surgery are discussed and listed. CONCLUSIONS: A thorough
      assessment of the defect and precise application of standard principles of
      hypospadias repair allows for successful correction of even complex hypospadias
      cripples.

PMID- 9773586
TI  - [The prenatal diagnosis of hydronephrosis: when and why NOT to operate?].
AB  - OBJECTIVES: To determine the proper timing and indications for pyeloplasty in
      infants with prenatally diagnosed unilateral hydronephrosis. METHODS: Examination
      of the 1) biological features of hydronephrosis which are unique to the newborn,
      2) natural history of non-operated newborn hydronephrosis, and 3) accuracy of
      tests which assess obstruction in hydronephrosis. RESULTS: Prenatally diagnosed
      unilateral hydronephrosis is a benign disease in most infants because obstruction
      is not present: the hydronephrosis will improve or disappear spontaneously, and
      impaired renal function will improve or normal renal function will remain stable.
      Consequently surgical treatment is not indicated; it will neither hasten nor
      improve the outcome. Unfortunately, the conventional tests for assessing
      obstruction are invalid in the infant and obstruction must be diagnosed or
      excluded by newly described protocols which use serial measurement of pelvic
      dilation, differential renal function and renal size. CONCLUSION: UPJ obstruction
      presents a diagnostic but not a therapeutic dilemma in infancy. True UPJ
      obstruction should be operated upon as soon after birth as possible to prevent
      renal deterioration. However, over 85% of infants with prenatally diagnosed
      hydronephrosis do not have a true obstruction and do not require surgery; they
      will improve spontaneously. The difficulty in deciding which patients require
      surgery can be minimized by a careful diagnostic protocol.

PMID- 9773588
TI  - [Posterior urethral valves: a change of concept].
AB  - OBJECTIVE: The basic question proposed in this article is whether early diagnosis
      and treatment of children with posterior urethral valves can prevent bladder and
      upper tract deterioration. If so, which is the best treatment? METHODS/RESULTS:
      Results with temporary urinary diversion for children with posterior urethral
      valves and renal insufficiency have not fulfilled expectations of an improved
      long-term outcome. Furthermore, there is mounting evidence that proximal urinary
      diversion with complete early bladder defunctionalization may result in reduced
      bladder capacity and compliance. In our experience early bladder cycling
      following valve ablation in the neonatal period is critical for the initiation of
      the healing process. Regardless of the initial appearance of the bladder and the
      status of the upper tract, early valve ablation may offer the best chance at
      functional recovery of normal bladder function, and restoration of upper tract
      function and anatomy without reconstructive surgery. In our series of 23 boys
      whose valves were resected at a mean of 21 days, bladder trabeculation resolved
      in 85% at one year. Follow up varied between 1 and 9 years. When compared to
      infants treated with urinary diversion, these children achieved superior potty
      training results. CONCLUSION: Bladder healing with early ablation seems to be
      dependent on bladder filling and emptying (cycling) with low outflow resistance.
      Ultimately, maximum recovery of renal function will depend on preventing the
      development of a hostile bladder. Early valve ablation may best achieve both
      goals of maximum bladder and renal functional recovery.

PMID- 9773587
TI  - [The prenatal diagnosis of hydronephrosis, when and why to operate?].
AB  - OBJECTIVES: To review the evaluation and management of the neonate and infant
      with prenatally detected hydronephrosis caused by a presumed ureteropelvic
      junction obstruction. METHODS: The literature is reviewed and the arguments in
      favor of expectant observation versus early operation are discussed. RESULTS: The
      meaning and severity of prenatally diagnosed hydronephrosis is determined after
      birth by evaluating: 1) the overall condition of the child; 2) the degree of
      dilatation on the ultrasonogram; 3) the differential renal function in the
      renogram and 4) the pattern of the excretory curve after furosemide in the
      renogram. CONCLUSION: It is understood that dilation per se does not mean
      obstruction but, if all other parameters indicate obstruction, we recommend early
      surgical treatment to prevent obstructive damage to the immature infant kidney
      and because better recovery of function is possible when surgery is done in the
      first year of life.

PMID- 9773589
TI  - [Utricular enlargements].
AB  - OBJECTIVE: Six cases of enlarged utricle are described, with special reference to
      the clinical, diagnostic and therapeutic aspects. METHODS/RESULTS: Utricular
      enlargement was suspected or confirmed radiologically in 5 cases and was
      confirmed by endoscopy in 5 cases. No patient was submitted to surgery. One
      patient underwent endoscopic removal of a utricular calculus. Prolonged medical
      treatment was required to maintain 5 patients free from infection. Good results
      were observed in 5 cases 1-9 years following diagnosis. CONCLUSIONS: Like most of
      the authors, we advocate treatment only for those cases with marked
      symptomatology, since children are at a very high risk for iatrogenic
      complications. Most of the cases, as shown in our series, do not require any
      treatment.

PMID- 9773590
TI  - [Urinary incontinence in myelodysplastic children, what is the role of the
      bladder neck "sling"?].
AB  - OBJECTIVE: The selection of patients amenable to treatment with a bladder neck
      sling remains a controversy. In this paper we review our experience with this
      technique and describe our patient selection criteria. METHODS: Since 1991, 30
      patients (24 females and 6 males) aged 4 to 20 years (mean 10) received a bladder
      neck sling as part of the surgical treatment for their urinary incontinence. The
      cause of incontinence was neurogenic in 28 of the 30 patients. The 6 male
      patients were prepuberal. All patients had a preoperative video urodynamic study.
      The criteria for increasing cervico-urethral resistance included a passive leak
      point pressure of < 50 cm H2O, stress leak point pressure of < 100 cm H2O,
      radiological evidence of an open bladder neck and stress incontinence regardless
      of the other urodynamic and radiologic parameters. The technical aspects of the
      procedure are described in detail. Augmentation cystoplasty was performed
      concomitantly in 29 patients. RESULTS: Patient follow-up ranged from 2 to 70
      months (mean 37.6). Twenty-eight patients (93%) were continent postoperatively.
      Two female patients remained incontinent at low leak point pressures. All
      patients emptied the bladder by intermittent catheterization. Twelve patients
      perform catheterization through the urethra without difficulty. CONCLUSION: The
      rectus fascia sling has several advantages over other surgical methods for
      increasing the cervico-urethral resistance. It is simple, effective, low-cost and
      has a low complication rate. In our view, the sling is the technique of choice
      for increasing cervico-urethral resistance in female and prepuberal male patients
      requiring a cystoplasty concomitantly.

PMID- 9773591
TI  - [Intermittent catheterization as the basis for treatment of neurogenic bladder
      during childhood].
AB  - OBJECTIVE: Neurogenic bladder (NB) frequently causes incomplete bladder emptying,
      which can lead to deterioration of the upper urinary tract (UUT), vesico-renal
      reflux (VRR) and incontinence. The aim of this study is to determine the degree
      of acceptance, performance and results of treatment of NB in children by
      intermittent catheterization (IC). METHODS: Of 121 children (50 girls and 38
      boys) with NB, 88 were managed by intermittent catheterization. The mean age at
      treatment was 5.2 years (range 20 days-13 years). PVC catheters were employed and
      reutilized for 3 or 4 weeks. Catheters were aseptic but not sterile.
      Antimicrobial prophylactic therapy was not administered except in patients with
      VRR. The statistical study was descriptive and results were compared using the
      Pearson chi square test. RESULTS: 90% had 4 or more catheterizations daily.
      Family and patient cooperation was good in 90% of the cases. Patients were
      managed by IC for a mean period of 4 years (range 1 month-14 years). Only two
      cases (2%) showed mild, transient complications (urethral pain and cystitis).
      Normal UUT remained normal in 85%; 45% with compromised UUT improved and 7%
      became worse. Of the children with no VRR, 94% did not develop this complication;
      VRR resolved in 72% of the cases (24% by IC alone and 48% with drugs or surgery).
      Only 12% were continent for more than 3 hours, which increased to 77% (64% by IC
      alone and 86% with drug therapy or surgery). Urethral sphincter urodynamics was
      the most important prognostic factor: patients with a lower urethral resistance
      showed better results for the UUT (p = 0.00373) and VRR (p = 0.00943). The
      results were also better in patients with normal UUT (p = 0.0003) and no VRR (p =
      0.009). CONCLUSIONS: IC is not limited by patient age, sex or sociocultural
      level. It preserves normal TUS and prevents VRR when instituted early, on
      demonstrating residual urine and high urethral resistance. IC alone or in
      combination with other treatments is the basic therapy in NB.

PMID- 9773592
TI  - [Primary vesicoureteral reflux in childhood. The current aspects and future
      outlook].
AB  - OBJECTIVE: To discuss the current aspects and the impact of innovations on the
      clinical, diagnostic and therapeutic aspects of vesicoureteral reflux (VUR).
      METHODS: The literature on Medline over the last five years are reviewed and the
      urodynamic findings in our series of children with VUR are analyzed. RESULTS:
      Fetal VUR and those diagnosed in children with a family history are currently
      considered to be the most interesting study groups from the clinical perspective.
      Renal scintiscanning, isotope-labelled cystography and urodynamic evaluation are
      well-established diagnostic methods that permit selecting the most appropriate
      treatment for patients with this anomaly. In our experience, 50.8% of the 128
      patients in whom a urodynamic study was performed, showed changes in lower
      urinary tract function. Innovations in open surgery have been scanty and
      endoscopic treatment is increasingly utilized, although the search continues for
      the ideal biological material. CONCLUSIONS: The new diagnostic methods utilized
      in the evaluation of children with VUR will permit a better understanding of the
      natural history of this anomaly lead to changes in the protocols that are
      currently used.

PMID- 9773593
TI  - [Vesicoureteral reimplantation in infants].
AB  - OBJECTIVE: To describe the results and follow-up of 34 vesico-ureteral
      reimplantations in infants. METHODS: From 1985 to 1994, 34 vesico-ureteral
      reimplantations (Cohen transtrigonal technique) were performed in 20 infants aged
      1-13 months. The indications for surgery were high grade congenital vesico
      ureteral reflux and breakthrough pyelonephritis that had presented in some cases
      despite prophylactic measures. RESULTS: At 4 years mean follow-up, all
      reimplanted ureters showed no reflux. One case with bilateral reimplantation was
      lost to follow-up. CONCLUSIONS: Many of the infants with vesico-ureteral reflux
      can be managed medically and the reflux will cease in some cases. But a few of
      them with difficult to control infections, can benefit from early surgery.

PMID- 9773594
TI  - [Allergy patients: caution in eating fish and celery! Food allergies caused by
      natural food components].

PMID- 9773595
TI  - [Cardiac pacemaker and internal defibrillators (ICD). Basic principles and new
      important developments, status 1998].
AB  - In recent years, treatment of cardiac arrhythmias with pacemakers and implantable
      cardioverter/defibrillators has become increasingly popular. Numerous technical
      developments have resulted in great advances in this area. International pacing
      letter coding for use with pacemakers defines the chamber(s) paced, the chamber
      in which the electrical activity is sensed, and the type of pacing. This also
      enables the family doctor involved in the care of the cardiac patient to identify
      the pacemaker system employed and provides him with initial orientation. New
      developments including VDD pacing, autocapture and autosensing are described and
      discussed. In a second part, the conditions for the use, and the manner of
      functioning, of modern implantable cardioverter/defibrillators are explained.

PMID- 9773596
TI  - [Sources of interference for cardiac pacemakers. Technical improvements of
      pacemakers--risks in the medical realm].
AB  - Such new technologies are associated with potential problems for patients with
      pacemakers which have not yet been adequately investigated. External sources of
      interference may inhibit or, in the case of dual chamber devices, trigger, the
      pacemaker, change its program or cause thermal damage to electrode tips leading
      to elevation of the stimulation threshold, or may destroy both hardware and
      software components. To prevent such problems, protective measures such as
      screening, sensitivity filters, asynchronous stimulation, and the bipolar
      electrodes have been developed. Detection by the pacemaker of a constant source
      of interference automatically activates an anti-interference circuit providing a
      fixed stimulating frequency. In contrast, interference by a pulsed or strongly
      amplitude-modulated signal can inhibit pacemaker function for a lengthy period
      and thus cause symptoms and possibly syncope.

PMID- 9773597
TI  - [Syncope in a pacemaker patient. Regular pacemaker follow-up is essential].

PMID- 9773598
TI  - [Color Doppler ultrasound of solid round liver lesions. Is detection of
      hepatocellular carcinoma possible?].

PMID- 9773599
TI  - [Genetic research makes new ways for preventing hypertension possible].

PMID- 9773600
TI  - [Single gene forms of hypertension. Glucocorticoid suppressible aldosteronism,
      Liddle syndrome et al].

PMID- 9773601
TI  - [Genetics of salt sensitivity. In which patients is salt restriction effective?].

PMID- 9773602
TI  - [Stroke and hypertension: challenge for molecular medicine].

PMID- 9773603
TI  - [Hemorrhoids--a commonplace affliction. Adequate drugs and application forms
      bring therapeutic success].

PMID- 9773604
TI  - [Disorders of porphyrin metabolism. 2: Diagnosis and therapy].

PMID- 9773605
TI  - [Fatty acids, insulin resistance and pancreatic beta cell function].

PMID- 9773606
TI  - [Role of fatty acids in hepatic and peripheral insulin resistance].

PMID- 9773607
TI  - [Gluco-lipotoxicity and gene expression in the pancreatic beta cell].

PMID- 9773608
TI  - [Long-term effects of fatty acids on the secretion and biosynthesis of insulin:
      consequences for type 2 diabetes].

PMID- 9773609
TI  - [The 1998 Apollinaire Bouchardat Prize. Autoantigens and type 1 diabetes: from
      physiopathology to therapeutics].

PMID- 9773610
TI  - [Nutritional education of diabetic patients].

PMID- 9773611
TI  - [Strategy of dietetic advice in type II diabetes. When the "standard" advice
      fails].

PMID- 9773612
TI  - [Ultimate treatment of type 2 diabetes: intensive insulin therapy or bariatric
      surgery?].

PMID- 9773613
TI  - [Review of the cooperative study of Veterans' affairs on the control and
      complications of type 2 diabetes, especially cardiovascular diseases].

PMID- 9773614
TI  - [Expression and regulation of the glucagon gene].

PMID- 9773616
TI  - [A new look at the mechanism of action of glucagon].

PMID- 9773615
TI  - [Post-translational maturation of proglucagon: variations in tissues and
      regulation pathways].

PMID- 9773617
TI  - [GLP-1 (7-36) amide [GLIP-glucagon like insulinotropic peptide] as a potential
      treatment for NIDDM].

PMID- 9773618
TI  - [The 1998 Maurice Derot Prize. [Diabetology-endocrinology in the same struggle].

PMID- 9773619
TI  - [Evaluation of insulin sensitivity: the HOMA and CIGMA models].

PMID- 9773620
TI  - [How and why to explore insulin secretion in the non-insulin-dependent diabetic].

PMID- 9773621
TI  - [Measurement of body composition and energy expenditure. Realization and
      importance in clinical practice].

PMID- 9773622
TI  - [Obesity in NIDDM: relevance of the control of fat mass or its its
      distribution?].

PMID- 9773623
TI  - [Genetic risk of non-insulin-dependent diabetes].

PMID- 9773624
TI  - [Economic impact of intensive insulin therapy in IDDM].

PMID- 9773625
TI  - [Which HbA1c to look at?].

PMID- 9773626
TI  - [Reevaluation of hypoglycemic risk in the course of intensive insulin therapy].

PMID- 9773627
TI  - [How are French insulin-dependent diabetics equilibrates: the experience of
      Diabcare France].

PMID- 9773628
TI  - [Is it possible to predict the success of an intensified program of insulin
      therapy?].

PMID- 9773629
TI  - [Effects of pramlintide, an analog of amylin, on the regulation of glycemia].

PMID- 9773630
TI  - [Evolution of the concept of insulin resistance in the BigPRO studies. The BigPRO
      Group. Biguanides and Prevention of the Risk of Obesity].

PMID- 9773631
TI  - [Benfluorex (Mediator): non-insulin-dependent diabetes and hypertriglyceridemia].

PMID- 9773632
TI  - [The clinical grading of subarachnoid hemorrhage].
AB  - Clinical grading scales for subarachnoid haemorrhages are exposed and discussed.
      These have been introduced by Botterell, in the middle fifties, to allow a better
      clinical evaluation, a more correct prognosis and, as a consequence, a more
      effective therapy. The most popular grading scale is, up to now, the one proposed
      by Hunt and Hess in 1968. The H-H scale divides patients in 5 groups or levels,
      whose severity is progressively increasing. A clinical study based on the H-H
      scale demonstrated that low grade patients (I-II) take advantage from early
      surgery; at the opposite, high grade patients (III-IV-V) achieve better results
      when treated with late surgery. To leave behind several difficulties in
      interpreting the clinical signs and therefore in using the H-H scale, in 1988
      Drake, on behalf of the World Federation of Neuro-logical Surgeons, published an
      "universal" grading scale for subarachnoid haemorrhage, based upon the well known
      Glasgow Come Scale score and on the finding of a motor focal deficit. The WFNS
      Scale is nowadays recommended for universal use, being easy and compatible with
      formerly employed scales.

PMID- 9773633
TI  - [Spontaneous subarachnoid hemorrhage: risk factors].
AB  - The precursive factors to SAH are classified into congenital, familial, intrinsic
      and extrinsic, pointing out the association between cerebral aneurysms and
      collagenopathies, genetic transmission disease, aneurysm features, habits and
      systemic disease.

PMID- 9773634
TI  - [Aneurysmic subarachnoid hemorrhage: epidemiology and cerebral circulatory
      physiopathology in the acute phase].

PMID- 9773635
TI  - [Cerebral blood flow in subarachnoid hemorrhage].
AB  - Cerebral blood flow (CBF) following subarachnoid haemorrhage varies according to
      the time of sampling, with regard to the time of bleeding, to clinical conditions
      of patients and to any possible occurrence of vasospasm. CBF is proportionally
      reduced upon clinical conditions, involves the totality of patients and
      represents a diffuse bilateral phenomenon, not dependent on the location of the
      aneurysm. Following events, such as vasospasm, may deteriorate haemodynamic
      conditions, especially when unstable. Thus, CBF monitoring is necessary and
      useful in these patients. The evaluation of this parameter, according to the
      metabolic demands, appears rather fundamental. Besides, during the first two
      weeks, all the available therapeutic strategies have to employed in order to
      achieve the best optimization of the CBF so as to avoid the occurrence or at
      least minimising the extent of ischemic cerebral lesions.

PMID- 9773636
TI  - [Physiopathology of non-traumatic subarachnoid hemorrhage: loss of
      consciousness].
AB  - The mechanisms underlying the loss of consciousness following the SAH can be only
      hypothesized at present time. The more convincing hypothesis appears to be the
      role of a cerebral circulatory insufficiency. Such an hypothesis stems from the
      following chain of events: 1) immediate increase of the intracranial pressure; 2)
      simultaneous constriction of the arteries of the poligone of Willis (early
      vasospasm); 3) decrease of the cerebral perfusion pressure; 4) cerebral ischemia.
      Different cerebral regions can be affected by the ischemia according to the
      prevalent location of the SAH, as for instance brain stem or telencephalon;
      consequently, different pathophysiological modalities can be responsible for the
      consciousness impairment. The entity of the SAH and of the consequent events
      responsible for the cerebral ischemia, influence the severity and reversibility
      of the loss of consciousness.

PMID- 9773637
TI  - ["Illustrative" clinical case of subarachnoid hemorrhage].

PMID- 9773638
TI  - [Immediate treatment of factors leading to death or sever cerebral damage in
      patients with subarachnoid hemorrhage].
AB  - Subarachnoid haemorrhage (SAH) is a medical emergency. Extracerebral factors may
      cause avoidable deaths, secondary cerebral damage and ultraearly rebleeding.
      Severe hypertension, hypotension, arrhythmias and pulmonary edema frequently
      occur; rapid referral with adequate treatment and monitoring (clinical, ABP, SO2,
      ECG) to neurosurgical centers is warranted. Practice guidelines should be
      addressed to obtain quality and continuity of management in the early diagnostic
      phase; intensive global medical approach should be ensured by neuranesthesists
      and intensivists to achieve optimal cerebral conditions before surgical or
      endovascular treatment.

PMID- 9773639
TI  - [Seizures associated with acute subarachnoid hemorrhage. Emergency diagnosis and
      treatment].
AB  - Seizures and convulsive status in patients with subarachnoid haemorrhage are an
      emergency. They are not only known to increase cerebral metabolic rate but also
      cerebral blood flow and intracranial pressure and rebleeding can occur in
      patients with an unclipped aneurysm. The goal of therapy is to stop the seizures
      minimizing the risk of secondary brain damage (hypoxia, hypotension, hypercarbia,
      hyperthermia). Several active drugs are available for treating seizures, it is
      important to identify the cause, prompt administration, monitoring the patients
      and choosing the one with less side effects.

PMID- 9773640
TI  - [Reasons in favor of lumbar puncture diagnosis (or lavage)].
AB  - In patients with strong suspicion of SAH, CT is the initial diagnostic procedure
      of choice. A lumbar puncture (LP) should be done if a CT is not available. If the
      patient has no focal deficit or papilloedema there is a little risk in LP. When a
      CT is negative there can be indication to do a LP: small leaks can be overlooked
      by CT, and they are often important premonitory events preceding larger and
      severe haemorrhages. The accuracy of CT in documenting SAH diminishes after 24
      hours: thereafter, diagnosis is often dependent on LP. In some cases LP can be
      useful because the procedure may alleviate headache and remove some blood. LP can
      also quantify cerebro-spinal fluid (CSF) pressure, provide a baseline for future
      CSF determination, and allow the study of some parameters like arachidonate
      metabolites, lactic acid, fibrinogen degradation products (FDP) and thrombin
      antithrombin complex (TAT).

PMID- 9773641
TI  - [Reasons against lumbar puncture diagnosis with cerebrospinal fluid drainage in
      subarachnoid hemorrhage].
AB  - The necessity of cerebral angiography or angio-MRI was assessed in patients with
      thunderclap headache in whom subarachnoid haemorrhage had been ruled out on CT
      findings. In this cases the cerebrospinal fluid examination could be dangerous
      because could reduce the intracranial pressure with consequent risk of aneurysm
      rupture. CSF drainage, although, improves the clinical conditions and the
      symptoms of the patients, seems to not reduce the incidence of permanent
      neurological deficits caused by vasospasm; on the contrary, it increases the
      incidence of hydrocephalus requiring shunt procedures. We conclude that routine
      ventriculostomy with external ventricular drainage should be considered for all
      patients with altered sensorium and acute hyrocephalus following subarachnoid
      haemorrhage, with improvement in outcome.

PMID- 9773642
TI  - [Differential diagnosis of subarachnoid hemorrhage].
AB  - The diagnosis of subarachnoid haemorrhage (SAH) presents in particular cases,
      some difficulties, even for neurosurgeons; the possibility that CT scan is
      negative during the first hours post SAH, represents a further problem; for these
      reasons the importance of lumbar puncture is stressed. In some cases an
      intracerebral clot may be misunderstood like an hypertensive haemorrhage. The
      recognition of the so called warning leaks, preceding the 40% of cases of "major"
      SAH, has a great importance for improving the final results, overall if is
      considered the high rate of mortality in the first 48 hours post a major SAH. For
      these reasons a peculiar attention has to be paid to these patients by the
      peripheral emergency rooms.

PMID- 9773643
TI  - [Diagnosis and general assessment of acute subarachnoid hemorrhage].
AB  - CT is still considered the first and most important examination in the case of
      subarachnoid hemorrhage. Frequently the CT findings are normal and no blood is
      detected in the CSF spaces. If that is the case, it will be useful to reevaluate
      the clinical presentation and it might be indicated to enhance the diagnostic
      evaluation with the use of lumbar puncture and CSF exam, or recurring to the
      study of the spine. In other cases, CT may detect slight modifications, with
      small blood collection in the CSF spaces, or more important bleeding in the CSF,
      intracerebral or intraventricular. Angiography represents the following
      diagnostic step.

PMID- 9773644
TI  - [Subarachnoid hemorrhage of unknown origin].
AB  - An analysis upon the incidence of sine materia SAH is done concerning the period
      before and after the availability of CT-scan. Furthermore, cases of SAH affecting
      the perimesencephalic cisterns, where the source of bleeding is in the majority
      not detectable are reported. The evolution of these SAH is generally favourable.
      Different groups of diffuse SAH, diagnosed sine materia at the first angiographic
      study, have to be submitted to a further short term angiography. In these cases,
      high risks to detect aneurysms affecting the anterior or posterior circulation
      are take into consideration. New technologies, i.e. angio-TC, provided by spiral
      TC, or angio-RM may help to achieve a more precise and reliable diagnosis in
      patients with sine materia SAH.

PMID- 9773645
TI  - [Early versus delayed surgery for treatment of aneurysmal subarachnoid
      hemorrhage].
AB  - Notwithstanding large cooperative epidemiological studies, in depth
      pathophysiological studies on subarachnoid hemorrhage, a unique surgical strategy
      has not emerged on the timing of aneurysmal subarachnoid hemorrhage. We define as
      early surgery the one which is practiced in the first 72 hours after the
      hemorrhage, and delayed surgery the one which is practiced more than 72 hours
      after the bleeding. Early and delayed surgery have both advantages and
      disadvantages, but as shown in the "International Cooperative Study on the Timing
      of Aneurysm Surgery" there are no significant differences in term of mortality
      and morbidity between early and delayed surgery. In fact the postoperative risk
      following early surgery is equivalent to the risk of rebleeding and vasospasm in
      patients waiting for delayed surgery. The novelty in the surgical timing of
      patients harboring an aneurysm which has bleed, is on one hand the "Ultra early
      surgery" which is performed not longer than 24 hours after the bleeding and on
      the other hand the attempt to individualize the timing of surgery on each single
      patient.

PMID- 9773646
TI  - [Therapeutic decisions and grading of subarachnoid hemorrhage].
AB  - Early admission and medical treatment can improve prognosis in patients with
      subarachnoid hemorrhage (SAH). In our Centre in 10 years, 595 patients with SAH
      have been treated: 422 were admitted within 24 hours (71%) and 498 (84%) within
      72 hours. 374 underwent surgical treatment: 283 within 48 hours and 91 underwent
      late surgery. Thirty-three patients underwent emergency surgery for intracranial
      hematomas, with a mortality rate of 30%. One hundred eighty-one patients in Hunt
      Hess grade I-II underwent early surgery. Mortality rate was 7%. Mortality rate
      for rebleeding, when surgery was delayed was more than 10%. Patients in Hunt-Hess
      grade III underwent early surgery in the majority of cases (68 out of 111). Only
      in 52% of cases surgical result was good. Thirty-four out of 108 in grade IV-V
      underwent early surgery, with a mortality rate of 45%. The analysis of general
      results shows that early surgery improves prognosis in Hunt-Hess grade III
      patients. Also patients in Hunt-Hess grade III-IV-V can take advantage of early
      surgery. Old age, arterial hypertension and angiographical vasospasm do not
      worsen prognosis even in patients operated on early. Endovascular treatment even
      in acute phase has improved results especially in cases of certain aneurysms
      types such as posterior circulation aneurysms.

PMID- 9773647
TI  - [Subarachnoid hemorrhage from ruptured aneurysms in elderly patients].
AB  - Advanced age is a recognized risk factor in patients with SAH. A strong
      correlation has been found between advanced age and impairment of consciousness
      at admission, presence of thick subarachnoid clot, intraventricular hemorrhage
      and acute hydrocephalus. Thus suggesting a more severe disease in elderly.
      Moreover the incidence of rebleeding increases with advancing age. As to the
      results of surgery a linear correlation between age and outcome has been found in
      most of series and it is difficult to identify a critical age. However the rate
      of patients with a poor outcome is significantly higher when an age cut off 60-65
      years is considered. Significant improvements have been obtained in the last 30
      years in elderly but mortality rate still remains at high level: in the order of
      20% in the patients 60-70 years old. For patients over 70 years only results from
      single series are available and these suggest favourable results in very selected
      cases. The introduction of GDC coil in the treatment of cerebral aneurysms has
      changed the management of most SAH patients and particularly of the older ones.
      The guidelines of current management of such patients followed at the Niguarda
      Hospital of Milan are presented. Age is one of the four "factors" taken into
      consideration for a selection of treatment (surgery or coil).

PMID- 9773648
TI  - [Giant aneurysms].
AB  - Giant aneurysms (> 2.5 cm) represent only 5-7% of all aneurysms. Nevertheless,
      their management is rather difficult due to their atypical natural history and
      peculiar treatment. Clinical history of giant aneurysms does not differ from that
      of the smaller ones regarding the incidence of subarachnoid hemorrhage, but it is
      complicated by much more neurologic deficits and by the occurrence of chronic
      intracranial hypertension syndrome. Diagnosis is essentially based upon CT scan
      and MR imaging in order to detect the morphological mass features and anatomical
      relationships, and upon angiography to appreciate characteristics regarding
      arterial flow and vascular relationships. The goal of treatment lies in the
      exclusion of the aneurysmal sac from the blood-stream and in the reduction of the
      mass effect. The treatment may be either surgical, endovascular or both. The most
      common surgical techniques consist in the direct occlusion of the neck of the
      aneurysm by means of metallic clips, or by fastening or trapping the carrier
      vessel or by removing the aneurysmal sac with the reconstruction of the arterial
      aspect when severe mass effect is detectable. The use of endovascular techniques
      goes for occlusion of the carrier vessel with balloons or for dynamic study of
      the collateral vascular districts with temporary occlusions.

PMID- 9773649
TI  - [Neuroradiologic strategy in patients with subarachnoid hemorrhage].

PMID- 9773650
TI  - [Surgical versus endovascular treatment in cerebral aneurysm. The opinion of a
      neuroradiologist].
AB  - Surgery is currently the treatment of choice for acutely ruptured aneurysms,
      representing an efficient option both in the short and long term. We believe that
      the endovascular option may be of help in high surgical-risk cases.

PMID- 9773651
TI  - [Surgical versus endovascular treatment in cerebral aneurysm. The opinion of a
      neurosurgeon].
AB  - The high risk of rebleeding of ruptured aneurysms imposes the need of their early
      exclusion from arterial circulation. The onset of endovascular technique of
      embolization gives a new chance, making, time by time, necessary the choice for
      the best treatment. The advantages and limits of surgical option are well known
      and consolidated. The results of endovascular technique are similar in the acute
      phase, but it lacks an adequate follow up and a clear definition of some
      technical knowledges. Clinical and anatomical data and a serious analysis of
      specific technical difficulties of both methods must condition the choice of
      treatment. Present experience allows us to give sure indications only for certain
      cases, whereas final landmarks are indisposable in many other situations.
      However, the team discussion between the neurosurgeon, the neuroradiologist and
      the neuroreanimator must be the crucial point of the decisional way in every
      single case.

PMID- 9773652
TI  - [Anesthesiologic problems in candidates for delayed surgery].
AB  - In preparing and maintaining a proper anaesthetic plan in the patient with
      subarachnoid haemorrhage undergoing delayed surgery, various concerns occur to
      the anaesthesist and the intensivist. These problems are related to the
      intracranic pathology but also to the structural, biochemical and functional
      changes occurring in a lot of organs and systems. Aim of anaesthetic approach is
      a correct preoperative evaluation and the maintenance of intracranic and systemic
      homeostasis. Systemically it is frequent the evidence of electrocardiographic
      abnormalities, due in same instances to myocardial hypoperfusion, of respiratory
      dysfunctions, of idroelettrolitic and metabolic changes leading to hypovolemia,
      hyponatremia and hypokalemia, and of coagulation disorders. With regards to the
      cerebral homeostasis, it is imperative to prevent rebleeding and vasospasm and
      the related neurologic damage. It is important the preoperative correction of the
      systemic dysfunctions, the prevention of the secondary neurologic damage, the
      stabilization of hemodynamic responses to various noxious stimuli, the provision
      of a good surgical field, and the achievement of a stable recovery; all these
      with the help of a proper clinical and instrumental monitoring.

PMID- 9773653
TI  - [Anesthesia in early surgery and endovascular therapy for aneurysmic subarachnoid
      hemorrhage].
AB  - Early surgery after SAH is frequently performed. The most important problems for
      anesthesiologists are the risk of rebleeding, the alteration of autoregulation
      and CO2 responsiveness, cardiac, respiratory and electrolytic alterations. In
      this phase the brain may be ischemic-edematous or haemorrhagic-compressive and
      the choice of anesthetic agent is made on the basis of cerebral conditions. The
      main goal is to control ICP and maintain adequate CPP. The endovascular treatment
      with Guglielmi detachable coils is usually performed in patients with poor
      neurologic and/or medical conditions. General anaesthesia under aggressive
      monitoring is advisable to control systemic pressure and to avoid movements.

PMID- 9773654
TI  - [Subarachnoid hemorrhage and pregnancy].
AB  - Intracranial haemorrhage from ruptured aneurysm or bleeding in arteriovenous
      malformation is rare, but may result in significant maternal and fetal mortality
      and serious neurological morbidity in survivors. Surgical intervention creates
      risks for the mother and her fetus, but is the best form of management. The
      anaesthetic procedure can present many clinical dilemmas, one of which is the
      role of induced hypotension. This review will focus on the diagnosis and
      management of this dramatic event.

PMID- 9773655
TI  - [Monitoring and protection of the central nervous system in subarachnoid
      hemorrhage during intensive care].
AB  - Subarachnoid hemorrhage has cerebral and systemic consequences as well. The main
      purpose of admitting a patient in the Intensive Care setting is to provide
      protection, mainly by stabilizing fundamental physiological parameters. There are
      both systemic parameters and cerebral parameters to be controlled continuously,
      and cerebral parameters may consider the brain as a whole (global cerebral
      parameters as intracranial pressure) or may provide information on specific
      areas. Cerebral protection may be achieved only when multiparametric monitoring
      is instituted, since only the combination of many physiologic parameters provides
      information capable of identifying, and hopefully of treating, deleterious
      derangements.

PMID- 9773656
TI  - [The use of jugular saturation in monitoring patients with subarachnoid
      hemorrhage ].
AB  - We evaluated the usefulness of monitoring jugular saturation (SjO2) in
      subarachnoid haemorrhage patients. SjO2 is an index of the global ratio between
      cerebral blood flow and metabolism. Low SjO2 identified global cerebral flow
      reduction, as due to low cerebral perfusion pressures or hypocapnia, but not
      regional ischemic phenomena related to vasospasm.

PMID- 9773657
TI  - [The use of TCD in intensive care and for identification of complications in
      subarachnoid hemorrhage ].
AB  - Transcranial Doppler (TCD) is at present the only exam to allow non-invasive,
      bedside monitoring of cerebral vasospasm after SAH. The high temporal resolution
      of this technique enables detection of fast flow-velocity changes occurring in
      intracranial arteries, as well as evaluation of vasomotive reserve and strength
      of autoregulation. TCD results concerning cerebral vasospasm evaluation are
      comparable to those obtained in angiographic studies; however the correlation
      between TCD data and clinical status is not always so strict. This difference
      could be explained by the fact that TCD measures flow velocity and not flow in
      intracranial vessels.

PMID- 9773658
TI  - [Strategy for intensive care in patients with subarachnoid hemorrhage].
AB  - Severe medical complications account for 20-30% of all deaths in patients with
      subarachnoid hemorrhage. High quality of intensive care is needed to prevent and
      correct pulmonary complications and electrolyte disturbances. Guidelines of
      intensive medical treatment should be defined to control intracranial
      hypertension and ischemic secondary cerebral damage in comatose patients.
      Extensive monitoring is necessary to achieve adequate observation in the
      perioperative period and safe treatment of vasospasm. A multidisciplinary
      approach in a critical area with intensive and sub-intensive beds, based on the
      cooperative role of neurosurgeons and anesthetists/intensivists, could improve
      the medical care, reducing complications, ICU stay and costs.

PMID- 9773659
TI  - [Subarachnoid hemorrhage: protective hypotension in delayed surgery].
AB  - Systemic hypertension is frequently observed in patients with subarachnoid
      haemorrhage (SAH). Continuing systemic hypertension might augment the risk of
      rebleeding and also increase the blood flow and blood volume, resulting in more
      marked cerebral edema and intracranial hypertension. However, reduction of blood
      pressure might also decrease cerebral perfusion pressure in patient with an
      impaired autoregulation and in this way enhance the risk of cerebral ischemia.
      Anti-hypertensive therapy is not recommended to prevent rebleeding after SAH. The
      agents of choice for reduction of arterial blood pressure might be mixed alfa and
      beta adrenergic antagonists and barbiturates.

PMID- 9773660
TI  - [Appropriate arterial pressure management for subarachnoid hemorrhage ].
AB  - A correct assessment of arterial pressure state during SAH is one of most
      critical issue in neurologic intensive care. It is important to evaluate two
      different clinical conditions: a) during SAH when the aneurysm is open, b) after
      aneurysmal clipping or embolization. The authors propose pressure parameters
      appropriated for SAH according to the timing of treatment so as to prevent and
      treat SAH complications.

PMID- 9773661
TI  - [Therapeutic strategy for vasospasm. Pharmacologic treatment].
AB  - A wide range of pharmacological treatment options for medical management of
      vasospasm, following SAH, are reported, i.e. calcium-antagonists, 21-amino
      steroids, fibrinolytics, vasodilators and CVF (venom of Cobra). Out of them,
      action mechanisms and clinical experiences are discussed, pointing out that
      surgical depletion of cisternal clots, hypertension, hypovolemia and hemodilution
      still represent a golden standard in the management of vasospasm due to SAH.

PMID- 9773663
TI  - [Pharmacologic therapy of subarachnoid hemorrhage].
AB  - Medical treatment of subarachnoid haemorrhage, is focused on the prevention of
      rebleeding and vasospasm, of damages of oxitading products, and on the
      improvement of general conditions of the patient. Some authors consider use of
      antifibrinolytic usefull to reduce the risk of rebleeding, but the percentage of
      hydrocephalus and ischemia are increased. In our Centre combination of nimodipine
      cloricromene and hemodilution is used for the prevention of vasospasm. We report
      conclusions about 216 patients in I-II-III grade of Hunt-Hess scale, treated
      before 48 hours from SAH. We obtained only 8% postspasm ischemias, with no
      neurological deficit, and only 23% of increased cerebral blood flow revealed by
      transcranial Doppler. Cloricromene is used only after aneurysm is occlused. It
      presents different action mechanisms. It is an inhibitor of platelet activation
      and aggregation, of cyclooxygenase and lipooxygenase activity, so reducing
      thromboxanes ratio. Phospholipase A2 inhibition it's possible but not
      demonstrated. It also interferes with phosphoinositoles path and so with
      proteinkinase C activity, and reduces hemostatic thrombotic balance activation
      and leukocyte endothelial adhesion and activation. It reduces, finally, the
      release of free radicals, cytokines inflammation amplyfing. The reduced damage to
      the endothelium allows the releasing of vasodilatatory agents like NO.

PMID- 9773662
TI  - [The prevention and treatment of vasospasm in subarachnoid hemorrhage].
AB  - The overall data concerning the incidence of angiographic and clinical vasospasm
      are reported. Furthermore, the pathogenetic mechanisms of vasospasm with regard
      to vasotoxic agents, vasogenic agents and CSF blockage are discussed together
      with the mechanisms affecting platelet aggregation, decrease of prostacyclins,
      and increase of endothelin. At present, therapeutic golden standard, i.e. (triple
      H therapy), calcium-antagonist, fibrinolytics and antioxidizing agents are
      debated concerning their clinical applications, first, during and after any
      possible surgical or endovascular treatment of the source of bleeding, i.e., the
      aneurysm.

PMID- 9773664
TI  - [Indications for steroid and tirilazad treatment in patients with subarachnoid
      hemorrhage].
AB  - Tirilazad mesylate, a nonglucocorticoid 21-aminosteroid, has been used in two
      randomized, double-blind, vehicle-controlled trials in Europe, Australia, New
      Zealand, and in North America in patients with aneurysmal subarachnoid
      hemorrhage. The first trial has been concluded, enrolled 1023 patients, and
      demonstrated a dramatic reduction in mortality from 27% to 3% (p = 0.01) in males
      receiving 6 mg/kg/day tirilazad for 10 days, when compared to vehicle-treated
      patients. There was also a less incidence of symptomatic vasospasm, and the
      frequency of hypertensive-hypervolemic-hemodilution therapy was significantly
      reduced. The reduction in mortality rate was remarkable, however the benefits of
      treatment with tirilazad were predominantly shown in men rather than in women.
      This clinical trial suggest that tirilazad mesylate, at a dosage of 6 mg/kg/day,
      improves overall outcome in aneurysmal subarachnoid hemorrhage patients. Further
      data from the North America trial and the trial in women receiving higher doses
      of tirilazad are still pending.

PMID- 9773665
TI  - [Neurogenic pulmonary edema during subarachnoid hemorrhage].
AB  - Neurogenic pulmonary oedema occurs in about 10% of SAH-patients being mainly due
      to cardiocirculatory changes related to imbalance of the central neurovegetative
      control. In particular, ESA should induce a sympathetic descending stress causing
      left ventricle failure. Physiopathologic, diagnostic and therapeutic data are
      briefly presented.

PMID- 9773666
TI  - [Subarachnoid hemorrhage and the heart].
AB  - Electrocardiographic abnormalities had been reported, in patients with
      subarachnoid hemorrhage, with variable percentage from 2% to 91%, according to
      several studies. The most common changes are T wave inversion, ST segment
      elevation or depression, QT prolongation, U waves, atrial flutter and
      fibrillation, ventricular fibrillation, supraventricular tachycardia, premature
      atrial and ventricular contractions. These findings occur within the first forty
      eight hours after the onset of the symptoms; they usually are benign and
      transient. In a small percentage of cases generally in severe ESA, the ECG
      changes are associated with ventricular asynergy, coronary vasospasm or
      subendocardic necrosis. The arrhythmias could be produced either by autonomic
      discharges to the heart, during increased sympathetic activity due to ESA, or by
      a damage of cerebral areas with arrhythmogenic capacity. The importance of ECG
      abnormalities towards mortality and morbidity in patients with ESA has not yet
      been cleared; however, a careful monitoring is recommended to prevent severe
      cardiac complications and to obtain an indirect, further evaluation of the
      neurologic pathology.

PMID- 9773667
TI  - [Hyponatremia in patients with subarachnoid hemorrhage].
AB  - Hyponatremia is a common feature after subarachnoid hemorrhage. Hyponatremia is
      complex in its origin because different neuroendocrine disturbances are involved:
      elements of inappropriate secretion of ADH, cerebral salt wasting, and blunted
      response of the reninangiotensin-aldosterone system may occur simultaneously.
      Hyponatremia is accompanied by hypovolemia which implies a major risk for
      vasospasm and cerebral infarction. Hyponatremia itself might cause cerebral edema
      and intracranial hypertension. Fluid restriction is therefore contraindicated in
      hyponatremia following subarachnoid hemorrhage because of the negative impact on
      intravascular volume. On the contrary, replacement of both volume and sodium
      should be vigorously accomplished.

PMID- 9773668
TI  - [Hydrocephalus and rebleeding in subarachnoid hemorrhage].
AB  - The main features of rebleeding and post-haemorrhagic hydrocephalus in case of
      subarachnoid haemorrhage following the rupture of an intracranial aneurysm are
      presented. In both cases frequency, causes, clinical events, prevention and
      therapy are discussed.

PMID- 9773669
TI  - [Evaluation of treatment results in patients operated for aneurysm].
AB  - The evaluation of the surgical results in patients operated on for intracranial
      aneurysms is still controversial, since a satisfactory method able to provide
      complete informations and ease to use is not still available. The more often used
      evaluation criteria provide standardized patterns, but the excessive
      simplifications affect the reliability of the final evaluation. Therefore, I
      suggest a brand new scale called Clinical Social Emotional Evaluation (CESE),
      based upon the following domains: neurological evaluation, psychomotor autonomy,
      return to prior job, behavioural and affective disorders, social reintegration
      and occurrence of seizures. In order to validate this scale, 190 patients
      operated on for intracranial aneurysms were assessed. Different scales provided
      different results. In detail, the number of the "best results" according to CESE
      was smaller (48%) when compared to the number provided by GOS (80%) and Rankin
      (62%). Nevertheless, the smaller amount of good results does not imply an overall
      worsening of the outcome. It is due to the different selection criteria employed
      by the diverse scales. Indeed, CESE selects groups of patients very
      homogeneously, whilst other scales include much more heterogeneous subjects.
      Thus, CESE would prove it-self to be a reliable, accurate and easy to use
      evaluation scale.

PMID- 9773670
TI  - [Targets and prevention of complications in nursing of subarachnoid hemorrhage].
AB  - A qualified nursing care is mandatory in patients after SAH. Clinical and
      instrumental monitoring are basilar to assure the rapid control of dangerous ICP
      or CPP changes and of epileptic crisis. Prophylaxis of infections is greatly
      minimized when coherent treatments are applied to any invasive devices, patient
      body, patient bed and UTI area. Many drugs can be useful to avoid ICP increases
      by tracheal suctioning and other sensorial stimulations. Having a trained staff,
      patient outcome can be improved.

PMID- 9773671
TI  - [Rehabilitative strategies in patients with subarachnoid hemorrhage].
AB  - The role of rehabilitative treatment in neurological disorders due to
      subarachnoid haemorrhage is described in acute, intermediate and chronic phases.
      A fourth phase, defined phase of diagnosis and treatment of cognitive and
      behavioural "cripto-deficits", is discussed. In each phase, emphasis is put on
      the organization of rehabilitative work which should always be the result of
      integrative team approach, to prevent and correct complications and to apply an
      holistic treatment (physical and cognitive). At present, in neurological
      rehabilitation, the most important requirement is no longer have the
      professionals (physiotherapists, speech and occupational therapists, etc.), but
      have a suitable environment and a good organisation of team planning and work.
      Neurosurgical centers is warranted. Practice guidelines should be addressed to
      obtain quality and continuity of management in the early diagnostic phase;
      intensive global medical approach should be ensured by neuroanesthesists and
      intensivists to achieve optimal cerebral conditions before surgical or
      endovascular treatment.

PMID- 9773672
TI  - [New strategies for treatment of intracranial aneurysm].
AB  - Prevision for the next future in a dramatic advances era we are living now has to
      be based upon fields consistently correlated to significative and immediately
      employable developments. Technical improvements in the next future, at the
      beginning of the third millennium, may schematically identified into two basic
      domains: the former, concerning surgical techniques; the latter, dealing with
      endovascular and neuroendoscopic techniques.

PMID- 9773673
TI  - [Prospective pharmacologic treatments for subarachnoid hemorrhage].
AB  - The aim of pharmacological therapy in subarachnoid haemorrhage (SAH) is to
      prevent cerebral ischemia and consequent events. Vasospasm, energy decrease,
      altered Ca++ homeostasis, lactic acidosis and free radicals are responsible for
      cerebral ischemic damage. Drug therapy in SAH is necessary before, during and
      after surgical treatment. Nimodipine is the only drug used today and supported by
      many clinical trials; scientific trials, on using known and new substances in SAH
      drug therapy, are in progress.

PMID- 9773674
TI  - Diurnal variation on the excretion patterns of fecal steroids in common marmoset
      (Callithrix jacchus) females.
AB  - The use of fecal steroid analysis to assess gonadal and adrenal function in
      primates has rapidly increased in recent years due to the ability to collect
      feces from nonhuman primates living in wild conditions. These techniques offer an
      exciting new potential for enhancing our knowledge of the endocrine status of
      free-living animals. Prior to using these techniques under field conditions, it
      is important to determine the diurnal variation of fecal excreted steroids for
      assessing possible time limitations on fecal collections. The following study
      investigates the diurnal frequency of defecation and patterns of steroid levels
      excreted in feces from four female common marmosets, Callithrix jacchus, living
      in a family group. These females represented three reproductive conditions: early
      pregnancy, ovarian cycling, and noncycling (postpubertal). Cortisol, estradiol,
      and progesterone were extracted and analyzed by enzyme immunoassay. Diurnal
      variations in steroid levels were found by ANOVA for cortisol and progesterone
      but not for estradiol. Significantly higher levels of cortisol were found in the
      afternoon, while the reverse was found for progesterone. All females showed the
      same pattern of steroid level change, except for cortisol in the pregnant female.
      Since all females defecated within the first hour after they awoke in the
      morning, this time was determined to be the most effective time to collect feces.
      The consistency of our findings reinforces the usefulness of this approach for
      studying reproductive and adrenocortical function in marmosets and also indicates
      that fecal collection should be limited to either morning or afternoon
      collections.

PMID- 9773676
TI  - Primigravidity, body weight, and costs of rearing first offspring in rhesus
      macaques.
AB  - Body size is associated with menarche and ovarian function, but the relationship
      to first conception is rarely examined. We conducted a longitudinal investigation
      of rhesus macaques, Macaca mulatta, to determine the effect of differences in
      body weight on both the age at first conception and survivorship of first
      progeny. Young females who became pregnant weighed significantly more than peers
      who remained barren, with weight changes for females who successfully raised
      offspring no different than those for females who did not produce offspring.
      Infant mortality among primiparae was not significantly greater than that among
      multiparae, although nearly twice as high. First-born males tended to have lower
      survivorship than first-born female offspring. We suggest that reproductive costs
      encountered by primiparous females are more likely to be modulated by immature
      neuroendocrine function than by inexperience, small body size, or infant suckling
      patterns. We conclude that body size influences probability of first conception,
      socioendocrine factors mediate the likelihood of infant survival, and primiparous
      production of male progeny seems to exert a greater reproductive cost than does
      production of female progeny.

PMID- 9773675
TI  - In situ hybridization (FISH) maps chromosomal homologies between Alouatta
      belzebul (Platyrrhini, Cebidae) and other primates and reveals extensive
      interchromosomal rearrangements between howler monkey genomes.
AB  - We hybridized whole human chromosome specific probes to metaphases of the black
      and-red howler monkey Alouatta belzebul in order to establish chromosomal
      homology between humans and black-and-red howlers. The results show that the
      black-and-red howler monkey has a highly rearranged genome and that the human
      chromosome homologs are often fragmented and translocated. The number of
      hybridization signals we obtained per haploid set was 40. Nine human chromosome
      probes gave multiple signals on different howler chromosomes, showing that their
      synteny is disturbed in A. belzebul. Fourteen black-and-red howler autosomes were
      completely hybridized by one human autosomal paint, six had two signals, three
      had three signals, and one chromosome had four signals. Howler chromosomes with
      multiple signals have produced 12 chromosomal syntenies or hybridization
      associations which differ from those found in humans: 1/2, 2/20, 3/21, 4/15,
      4/16, 5/7, 5/11, 8/18, 9/12, 10/16, 14/15, and 15/22. The hybridization pattern
      was then compared with those found in two red howler taxa and other mammals. The
      comparison shows that even within the genus Alouatta numerous interchromosomal
      rearrangements differentiate each taxa: A. belzebul has six unique apomorphic
      associations, A. seniculus sara and A. seniculus arctoidea share seven derived
      associations, and additionally A. seniculus sara has four apomorphic associations
      and A. seniculus arctoidea seven apomorphic associations. A. belzebul appears to
      have a more conserved karyotype than the red howlers. Both red and black-and-red
      howlers are characterized by Y-autosome translocations; the peculiar chromosomal
      sex system found in the red howler taxa could be considered a further
      transformation of the A. belzebul sex system. The finding that apparently
      morphologically similar or even identical taxa have such extreme genomic
      differences has important implications for speciation theory and neotropical
      primate conservation.

PMID- 9773677
TI  - Effects of radio transmitter weight on a small nocturnal primate.
AB  - An increasing number of primatologists have begun using radio telemetry to study
      the behavioral ecology of nocturnal prosimian primates. Radio telemetry has
      enabled the collection of data on these nocturnal and cryptic prosimians that was
      previously difficult or impossible to otherwise obtain. A critical assumption of
      studies employing radio telemetry is that the radio transmitters have no
      appreciable negative effects on the study animals and the data being collected
      are not being biased by the presence of radio transmitters. This assumption is
      made because comparable data from a non-radio-collared control group are
      impossible to obtain. In an attempt to determine the tolerable weight limit for
      radio collars for a small nocturnal primate, the spectral tarsier, Tarsius
      spectrum, a comparison of the behavior and body weight of individuals wearing
      collars of two different weights was conducted. This study was conducted in
      Tangkoko Dua Saudara Nature Reserve in Sulawesi, Indonesia. A total of 16
      individuals from seven groups were trapped in mist nets, radio-collared, and
      observed using focal follow sampling between April 1994 and June 1995. Each
      individual was observed for 4-6 months depending on the life span of the radio
      collar battery. The two radiocollar weights appeared not to affect spectral
      tarsiers differentially. Average body masses in neither set of subjects differed
      between the days collars were attached and 6 months later, when they were
      removed. No differences in activity patterns, home range size, or prey capture
      rate were detectable between subjects wearing the different transmitters. These
      results suggest that the heavier radio collars used in this study did not have
      any appreciable effects on the behavioral patterns of this primate.

PMID- 9773678
TI  - Changes in the activity budget of cycling female chimpanzees.
AB  - This study is a preliminary report on the time allocated to various activities by
      female wild chimpanzees (Pan troglodytes schweinfurthii) during their sexual
      cycle. Cycling females with maximal tumescence (estrous females) tended to spend
      more time moving than cycling females with quiescent sexual skin (anestrous
      females). Although there was no statistically significant decrease in any
      specific activity that corresponded to the increase in time spent moving, feeding
      time did decrease in four of the five females. The frequency of approach by
      females toward males and the frequency of approach by males toward females
      significantly increased when females were in estrus. Direct aggression by males
      occurred more frequently toward estrous females than toward anestrous females.
      The copulation frequency and the frequency of approach to males was not
      significantly correlated with the increase in time spent moving. There was a high
      but not significant correlation between the time spent moving and the frequency
      of direct aggression by males toward females. Mating effort, feeding competition,
      male aggression, and other possible reasons that might explain the increase in
      moving time are discussed.

PMID- 9773679
TI  - Applying GPS to the study of primate ecology: a useful tool?
AB  - Data on the spatiotemporal distribution of resources can be collected and plotted
      using GPS (global positioning system) and GIS (geographical information system)
      technologies. By combining such data with information on foraging and ranging
      behavior of nonhuman primates, one can analyze the influence of resource
      distribution on social organization and group cohesion. We investigated the
      abilities of a three-channel GPS receiver to collect location data under varying
      canopy densities in both temperate and tropical forests. Eighty randomly selected
      points were sampled in a beech-maple forest in northeast Ohio, USA; 65 points
      also were sampled at several tropical forests in Costa Rica and Trinidad. At each
      point we attempted to obtain a GPS position fix; we also determined the speed of
      satellite acquisition and measured canopy density using a spherical densiometer.
      The ability to obtain a reading differed greatly between the two forest types
      (chi(2) = 53.79, P < 0.001). Ninety-seven percent of all attempts were successful
      in the temperate forest, whereas only a 34% acquisition rate was obtained in the
      tropical forests. Logistic regression showed that the probability of obtaining a
      reading in Neotropical forests was 75% but only when canopy cover was less than
      20%. Thus, these minimal-channel GPS units may be of limited utility for
      behavioral ecologists working in closed-canopy Neotropical forests.

PMID- 9773680
TI  - Monitoring pregnancy in twinning pygmy loris (Nycticebus pygmaeus) using fecal
      estrogen metabolites.
AB  - Estrone and estrone conjugates were measured in the feces of three female pygmy
      lorises (Nycticebus pygmaeus) throughout estrus, pregnancy, and the postpartum
      period. Two females gave birth to twins, while the third had a single stillborn.
      A comparison between the hormonal profiles of these three pregnancies with each
      other and with previously reported pregnancies resulting in singletons or twins
      [Jurke et al., American Journal of Primatology 41:103-115, 1997] revealed a
      characteristic pattern of hormonal excretion. This report adds data to and
      confirms previous claims that monitoring estrone in this species provides a tool
      to assess gestation length (via determination of estrus period) and to predict
      the date of parturition and the number of offspring. However, there was an
      exceptional case of a pregnancy which had the hormonal appearance of a twin
      pregnancy but resulted in a single stillborn infant. This case prompted us to
      search for new insights into the characteristics and the origin of the estrogens
      that are excreted into the feces. Aromatase activity was evaluated in five
      partial placentae.

PMID- 9773681
TI  - Evidence that TGF-beta should be a therapeutic target in diabetic nephropathy.

PMID- 9773682
TI  - Hepatocyte growth factor: mesenchymal signal for epithelial homeostasis.

PMID- 9773683
TI  - The structure-function relationship in preeclampsia.

PMID- 9773684
TI  - Evaluation of patterned stimulation for use in surface functional electrical
      stimulation systems.
AB  - The rapid onset of muscle fatigue is one of the major limiting factors when using
      electrical stimulation to restore functional movement in individuals with a
      neurological deficit. It has been proposed that muscle efficiency can be improved
      by using variable frequency pulse trains (VFT), consisting of repeated doublets,
      rather than a constant frequency train (CFT) of stimulating impulses. The aim of
      this study was to test this hypothesis. Experiments were conducted on fifteen non
      impaired and one spinal cord injured subjects. It was shown that a VFT delivering
      the same electrical energy with a CFT produces a relative increase in muscle
      output, attaining a maximum for VFTs composed of doublets with an inter-pulse
      interval of 5 ms. It was also shown that this effect is highly dependent on the
      experimental conditions and especially the intensity of applied stimulation and
      this effect diminishes at high intensity levels. We suggest that any improvement
      in muscle output observed when using a VFT can be attributed to changes in motor
      unit recruitment and is not an intrinsic property of the muscle. Our results show
      that there is practically no benefit in using VFTs for alleviating the problem of
      fatigue in functional electrical stimulation systems.

PMID- 9773685
TI  - Distance of foetal movement measured using the analytical signal derived from non
      directional Doppler sound.
AB  - Foetal heart rate (FHR) monitoring using the Doppler shift resulting from the
      movements of the foetal heart is a standard examination in most obstetrical
      wards. Other movements also give rise to a low frequency Doppler shift. These
      signals are incompletely understood. Their characteristics may offer a way for
      diagnostic exploitation through complementing or replacing time consuming
      ultrasound observation of foetal movements. It is shown that a wealth of
      information is contained in these signals which can easily be extracted on line
      by a standard PC computer using straightforward methods of signal processing. In
      its amplitude an ultrasonic Doppler signal contains information concerning the
      size of the reflector in movement and speed as frequency. The displacement of the
      reflector can also be derived from the phase evolution of a complex Doppler
      signal. Examples of signals generated by various types of foetal activity are
      shown and analyzed.

PMID- 9773686
TI  - MAVIS: a non-invasive instrument to measure area and volume of wounds.
      Measurement of Area and Volume Instrument System.
AB  - Accurate measurement of the physical size of wounds is vital for assessment of
      the progress of healing. An instrument has been developed to measure area and
      volume of skin wounds, ulcers, and pressure sores. MAVIS--Measurement of Area and
      Volume Instrument System-is based on the principle of colour coded structured
      light. A set of parallel stripes of alternating colours is projected onto the
      wound area at an angle of approximately 45 degrees and is recorded by a CCD
      camera. From the known position of the focal points of projector and camera, and
      from the observed intersection points of the stripes of light with the wound
      surface, a computer calculates a three-dimensional map of the observed wound. The
      volume of the wound is defined as the volume of the region sandwiched between the
      observed surface and the original healthy skin surface which is simulated by
      cubic spline interpolation. This paper compares the performance of the instrument
      with three traditional wound measurement techniques using results obtained from a
      clinical trial involving 50 patients. Traditional area measurement techniques
      such as transparency tracings produce results with standard deviations between 4%
      (large wounds) and up to 20% (small wounds) of the measured mean value. MAVIS
      measurements reduce these standard deviations by 3-5%. Measuring the wound volume
      by alginate casts produces errors in volume figures between 5% and 40%. Standard
      deviations of MAVIS results are 5% smaller on average. The results demonstrate
      that MAVIS yields more reproducible results with a minimum of inter-observer
      error. The instrument does not make contact with the wound, provided visual
      records and measurements are made in less then 5 min. It is not suitable for
      undermined, very deep or very large wounds.

PMID- 9773687
TI  - Biomechanical and structural assessment of transluminal angioplasty.
AB  - The increasing incidence of stroke is frequently maintained by the processes
      narrowing precerebral and cerebral arteries. That is why the surgical treatment
      of cerebrovascular disorders has increasingly included percutaneous transluminal
      angioplasty. However, the influence of transluminal angioplasty on the
      biomechanical properties of arterial wall have not been assessed so far. The
      cylindrical segments of left and right internal carotid artery, middle cerebral
      artery, anterior cerebral artery, vertebral artery, basilar artery and posterior
      cerebral artery were taken from 40 autopsy subjects aged from 20 to 75 who had no
      systemic lesions with the exception of atherosclerosis. The biomechanical
      examination and experimental transluminal angioplasty of the segments were
      carried out with special equipment developed for this purpose. The data were
      obtained using a TV camera assisted measurement and morphometric and histological
      methods. The examination of the biomechanical properties repeated after the
      experimental transluminal angioplasty shows the additional relative strain of the
      external diameter of vessel and the decrease of the arterial wall tangential
      elastic modulus in the circumferential direction. This suggests that if
      transluminal angioplasty results in sufficient structural damage of the arterial
      wall than there will be an improvement in the ability of the vessel diameter to
      increase under normal blood pressure conditions.

PMID- 9773688
TI  - Disposable bedpads for incontinence: predicting their clinical leakage properties
      using laboratory tests.
AB  - A multi-centre project has been run to identify laboratory tests capable of
      predicting the leakage performance of disposable incontinence bedpads. Each of 95
      subjects tested each of six products for a week in turn and reported whether or
      not they and/or their carers found the leakage performance of each product
      acceptable. In addition, carers noted the severity with which individual used
      bedpads had leaked so that, when they had been weighed, their leakage performance
      could be determined as a function of urine weight. These clinical data were
      compared with results from the 16 different laboratory tests used routinely for
      bedpad evaluation in three hospital laboratories. Each test was evaluated by
      seeing how well the data it yielded correlated with the clinical test data. No
      individual test was very successful at predicting the performance of bedpads when
      used as sole protection but a combination of an absorption capacity test and an
      absorption time test predicted the percentage of users/carers finding leakage
      performance acceptable, accurate to within +/- eight percentage points for all
      six test products. A different absorption capacity test proved most successful
      for bedpads used as back-up to body-worn products. It predicted the percentage of
      users/carers finding leakage performance acceptable, accurate to +/- five
      percentage points for all six products.

PMID- 9773690
TI  - Precise and fast calculation of the motor unit potentials detected by a point and
      rectangular plate electrode.
AB  - To reduce the time of computation of a motor unit potential (MUP), the shape of
      intracellular action potential (IAP) and (or) MU anatomy are generally
      simplified. A method of MUP presentation is suggested. It provides accuracy of
      the MUPs calculated for any distance and size of rectangular electrodes together
      with considerably reduced computational load and time. No simplification of the
      IAP shape or location of muscle fibres of different diameters and lengths is
      required. The MUP generated by N temporally and spatially dispersed single fibre
      action potentials is considered to be the output signal of a linear time-shift
      invariant system for potential generation. The input signal is the first temporal
      derivative of the IAP. The common impulse response (CIR) is the sum of potentials
      produced at the electrode by N pairs of dipoles propagating from the motor end
      plates to the ends of the corresponding fibres. The potentials of each dipole at
      the rectangular plate electrode are determined analytically. Thus, the MUP is
      calculated as a single convolution between the input signal and CIR for a
      rectangular electrode of any size.

PMID- 9773689
TI  - Finite element modelling of a residual lower-limb in a prosthetic socket: a
      survey of the development in the first decade.
AB  - A review is presented of the existing finite element models developed from 1987
      to 1996 for the biomechanics of lower-limb prostheses. Finite element analysis
      can be a useful tool in investigating the mechanical interaction between the
      residual limb and its prosthetic socket, and in computer-aided design and
      computer-aided manufacturing of prosthetic sockets. Various assumptions and
      simplifications are made in these models to simplify the actual problem with
      complex geometry, material properties, boundary and interfacial conditions, as
      well as loading situations. The analyses can provide the information on the
      stress distribution at the stump/socket interface and within the residual limb
      tissues. More recently, nonlinear models have been developed taking into
      consideration the process of socket rectifications, the slip/friction conditions
      and material large deformation. The models so far developed have provided some
      basic understanding of the biomechanics. Comparison of the predictions of these
      models with experimental measurements indicated that the predicted stresses were
      within the ranges measured, although one-to-one correspondence was difficult to
      achieve. Further research is still required in order to improve these models to
      obtain higher precision in the results taking into account nonlinear and dynamic
      effects.

PMID- 9773691
TI  - A mechanistic model of plasma filtration.
AB  - A model describing the sieving and transmembrane pressure behavior of plasma
      filtration is developed and numerically simulated. The model assumes a
      mechanistic criteria for particle passage through a membrane with cylindrical
      pores. The initial pore diameter distribution and porosity are assumed to be
      known. Model inputs include the particle diameter distribution, concentration and
      total flow rate of the permeate plasma solution. Outputs of the model include
      transmembrane pressure, the time-averaged sieving coefficients, and size
      distributions of the deposited particles and accumulated filtrate particles.
      Optimal filtration is characterized by high, stable sieving coefficients for
      desired particles, high retention of larger particles and relatively small
      increases in transmembrane pressure. These characteristics are realized for
      membranes with mean pore diameters equal to or slightly larger than mean permeate
      particle diameters. Simulations demonstrate that the incorporation of membrane
      properties into models of plasma filtration is both significant and readily
      possible.

PMID- 9773692
TI  - Reproducibility of techniques using Archimedes' principle in measuring cancellous
      bone volume by L. Zou, R. D. Bloebaum and K. N. Bachus.

PMID- 9773693
TI  - The safety of epidurals placed during general anesthesia.

PMID- 9773694
TI  - Regional anesthesia does not significantly change surgical time versus general
      anesthesia--a meta-analysis of randomized studies.
AB  - BACKGROUND AND OBJECTIVES: The major determinant of variable operating room costs
      is surgical time. A number of factors contribute to surgical time. This study was
      designed to determine whether regional anesthesia decreases surgical time when
      compared with general anesthesia over several surgical procedures. METHODS: A
      search was conducted for clinical trials that reported surgical times and which
      compared outcomes from regional versus general anesthesia. A meta-analysis of
      these trials was completed to determine whether, on average, among many surgeons
      and surgical procedures, the use of regional anesthesia affects surgical time.
      Confidence intervals were calculated and random effects meta-analysis was used to
      pool results. RESULTS: Twenty-six studies (with 1,874 patients) were used in the
      meta-analysis. Regional anesthesia does not significantly decrease surgical time
      versus general anesthesia (mean general minus regional difference was 1.7
      minutes, 95% confidence interval -0.5 to 3.9 minutes). CONCLUSIONS: Overall, the
      use of regional anesthesia does not significantly decrease surgical time.

PMID- 9773696
TI  - The paravertebral nerve root block for inguinal herniorrhaphy--a comparison with
      the field block approach.
AB  - BACKGROUND AND OBJECTIVES: Our objective was to evaluate the efficacy of the
      paravertebral block for inguinal herniorrhaphy by comparison with the well
      established field block. METHODS: Thirty patients undergoing inguinal
      herniorrhaphy were randomly divided into two groups. Group A (n = 15) received
      paravertebral block of the ipsilateral nerve roots of T12, L1, and L2. Group B (n
      = 15) received field block. Each block was evaluated in terms of the degree of
      patient discomfort associated with surgical manipulations, requirement for
      supplemental anesthetic, the degree of patient discomfort associated with block
      performance, and the overall degree of patient satisfaction. RESULTS: Both
      approaches were successful in blocking somatic sensory fibers. The paravertebral
      approach showed a significantly higher success rate than the field block (P <
      .01), regarding frequency of pain relative to surgical manipulation of the
      spermatic cord, hernial sac, and also in terms of need to supplement the surgery
      with local anesthetic (P < .01). The paravertebral block required significantly
      less local anesthetic and less needle insertions than the field block.
      CONCLUSIONS: The paravertebral nerve root block proved to be superior to the
      field block, to be devoid of side effects, and was acceptable to the patients.

PMID- 9773695
TI  - Comparative toxicity of glucose and lidocaine administered intrathecally in the
      rat.
AB  - BACKGROUND AND OBJECTIVES: Glucose is a common component of anesthetic solutions
      used for spinal anesthesia. However, its possible contribution to recent injuries
      occurring with spinal anesthesia has not been adequately addressed. Accordingly,
      the present studies compare the functional and morphologic effects of
      intrathecally administered glucose with those of lidocaine. METHODS: Twenty rats,
      implanted with intrathecal catheters, were divided into three groups to receive a
      1-hour infusion of 5% lidocaine (n = 6), 10% glucose (n = 7), or normal saline (n
      = 7). Four days after infusion, animals were evaluated for persistent sensory
      impairment using the tail-flick test. Three days later, the animals were
      sacrificed, and the spinal cord and nerve roots were examined by a
      neuropathologist blinded to the solution received and the results of sensory
      testing. RESULTS: Lidocaine-treated animals exhibited persistent sensory
      impairment, whereas glucose- and saline-treated animals did not. Neuropathologic
      evaluation revealed moderate to severe nerve root injury in lidocaine-treated
      animals. Histologic changes in glucose- and saline-treated animals were minimal,
      similar, and restricted to the area adjacent to the catheter. Morphologic damage
      associated with lidocaine preferentially affected the nerve roots, with relative
      sparing of the spinal cord and dorsal root ganglia. CONCLUSIONS: These results
      suggest that, at clinically relevant concentrations, glucose does not induce
      neurologic injury, providing indirect evidence that recent clinical injuries
      occurring after spinal anesthesia resulted from a neurotoxic effect of the local
      anesthetic. Additionally, the present studies suggest that deficits resulting
      from neurotoxicity of intrathecally administered anesthetic result from injury to
      the axon.

PMID- 9773697
TI  - Intrathecal sufentanil and epidural bupivacaine for labor analgesia: dose
      response of individual agents and in combination.
AB  - BACKGROUNDS AND OBJECTIVES: Combinations of local anesthetics and opioids are
      frequently used during spinal and epidural analgesia for the relief of labor
      pain. This combination allows for a dose-sparing effect which may reduce
      potential side effects or toxicity. The precise nature of the interaction between
      opioids and local anesthetics in the clinical setting, i.e., additivity versus
      synergism, has not been established. This trial was designed to utilize a
      validated technique of analysis of drug interactions, isobolography, to
      investigate this interaction. METHODS: One hundred healthy laboring patients at
      term receiving a combined spinal and epidural technique were divided into nine
      groups as follows: intrathecal sufentanil 2, 5, or 10 microg (2 mL volume) and
      epidural saline (10 mL); epidural bupivacaine 5, 12.5, or 25 mg and intrathecal
      saline (2 mL volume); or combination of l, 2.5, and 5 microg intrathecal
      sufentanil plus 2.5, 6.25, or 12.5 mg epidural bupivacaine, using similar
      volumes, respectively. All drugs were administered in a randomized, double-blind
      fashion. Pain relief scores were assessed 20 minutes after drug injection, and
      isobolographic analysis was utilized to determine the nature of the interaction.
      RESULTS: The ED50 of intrathecal sufentanil alone was 2.3 microg (95% CI 1.7
      3.2), and the ED50 for epidural bupivacaine was 24 mg (95% CI 12-50). The
      combined sufentanil and bupivacaine fractional dose ED50 (in fractions of the
      single-dose ED50 values) was found to be approximately one-third and one-tenth of
      the single drug fractional dose, respectively: sufentanil 0.85 microg (0.36) and
      bupivacaine 2.2 mg (0.09). The duration of analgesia was nearly equivalent in all
      sufentanil-alone groups (83, 102, and 99 minutes); a dose-response effect was
      more apparent in the bupivacaine group (35, 42, and 74 minutes; P = .006) and the
      combination group (60, 79, 101 minutes; P = .028). Isobolography showed the
      combination dose to lie well within the area of synergism; however, the 95%
      confidence limits cross the line of additivity thus a pure additive interaction
      cannot be excluded. CONCLUSIONS: Markedly reduced doses of these drugs in
      combination can be used to provide adequate analgesia during labor compared with
      either single drug alone.

PMID- 9773698
TI  - Intrathecal local anesthetic distribution with the new spinocath catheter.
AB  - BACKGROUND AND OBJECTIVES: Microcatheters have been linked in some cases to the
      development of cauda equina syndrome, which may be further traced to the
      maldistribution of the local anesthetic. A long injection time via the
      microcatheters contributes to the inadequate mixing. With the new Spinocath
      catheter, considerably shorter injection times can be achieved due to larger
      internal size. This study examined whether this leads to more homogeneous
      intrathecal distribution without causing greater trauma to the dura. METHODS: In
      an in vitro model of the spinal canal, the distribution of hyperbaric and
      isobaric 0.5% bupivacaine (2.5 mL) as well as 5% lidocaine (2.5 mL) was examined
      after injection via the 28-gauge CoSpan catheter (Kendall, Healthcare, Mansfield,
      MA), the 22-gauge Spinocath catheter (Braun, Melsungen, Germany), and a 29-gauge
      Quincke needle (Becton Dickinson, Rutherford, NJ). The local anesthetic
      concentration in the vertebral interspaces T12-L1 to L5-S1 was measured via gas
      chromatography 3 and 10 minutes after injection. In addition, the morphologic
      puncture characteristics of human dura were examined with the halftone electron
      microscope, after puncture with the catheters and needle. RESULTS: After
      injection through the 28-gauge CoSpan catheter, caudal segments of the spinal
      canal showed peak concentrations up to a maximum of 1,147 microg/mL bupivacaine
      or 8.5 mg/mL lidocaine with hyperbaric solutions, which did not decrease over the
      10 minutes of measurement. After injection through the Spinocath catheter, there
      was a homogeneous distribution with data peaks of approximately 350 microg/mL
      bupivacaine or 4.2 mg/mL lidocaine similar to the data found after injection
      through the spinal needle. CONCLUSIONS: The new Spinocath catheter allows a
      better mixing of the local anesthetic with the cerebrospinal fluid. Because of
      significantly shortened injection times, hyperbaric solutions also show a more
      homogeneous distribution. Although the Spinocath catheter has a larger inner
      diameter than the other microcatheters, it appeared to cause less trauma to the
      dura.

PMID- 9773699
TI  - Analgesic effect of interscalene block using low-dose bupivacaine for outpatient
      arthroscopic shoulder surgery.
AB  - BACKGROUND AND OBJECTIVES: Although interscalene brachial plexus block (ISBPB) is
      often used to provide anesthesia for arthroscopic shoulder surgery, its selective
      analgesic effect, provided by low-dose local anesthetic, has not been studied. We
      hypothesized that ISBPB using a low volume and low concentration of bupivacaine
      can provide effective postoperative analgesia for shoulder surgery without
      producing significant sensory or motor block elsewhere. METHODS: In this double
      blind study, 30 outpatients scheduled to undergo shoulder arthroscopy were
      randomly assigned to receive either an ISBPB with 10 mL 0.125% bupivacaine with
      epinephrine 1:400,000 (n = 15) or 10 mL of normal saline (n = 15). The block was
      performed preoperative, prior to a standardized general anesthetic. Postoperative
      pain scores, imorphine and oral analgesic consumption, recovery profile, and
      patient satisfaction were recorded. RESULTS: In the ISBPB group, verbal analog
      pain scores within 120 minutes after surgery were lower, morphine consumption in
      the postanesthesia care unit was significantly lower (2.7+/-2.6 mg vs 9.5+/-5.2
      mg), the time to postoperative administration of the first systemic or oral
      analgesic was significantly longer (141+/-182 minutes vs 13+/-10 minutes), the
      degree of motor and sensory block 120 minutes after surgery was minimal, time to
      reach hospital discharge criteria was earlier, and patient satisfaction with
      postoperative analgesia at 24-hour follow-up was greater. Thirty-three percent of
      the patients receiving ISBPB did not require any analgesic prior to hospital
      discharge. CONCLUSIONS: Interscalene brachial plexus block with low-dose
      bupivacaine is a useful and selective analgesic technique for outpatient shoulder
      arthroscopic surgery.

PMID- 9773700
TI  - The safety and efficacy of intrabursal oxycodone and bupivacaine in analgesia
      after shoulder surgery.
AB  - BACKGROUND AND OBJECTIVES: Peripherally administered opioids, e.g., intra
      articular morphine, exert their analgesic action on local opioid receptors. The
      present study investigated the safety and efficacy of intrabursal oxycodone and
      bupivacaine in comparison with bupivacaine infiltration and interscalene brachial
      plexus block in conjunction with shoulder surgery. METHODS: A prospective,
      randomized study was conducted in 45 patients (15 per group) undergoing elective
      shoulder surgery during general anesthesia. At the end of the surgery, patients
      received either 10 mL 0.5% bupivacaine (group B) or 5 mg oxycodone and 10 mL 0.5%
      bupivacaine (group OB) in the subacromial bursa; interscalene plexus blocks were
      performed preoperative (group IPB). Postoperative analgesia was provided by
      patient-controlled analgesia, and the amount of intravenous fentanyl used during
      the total perioperative period was recorded. Postoperative pain was assessed by a
      visual analog scale. RESULTS: The total fentanyl consumption was lower in groups
      OB and IPB than in group B, and the difference reached statistical significance
      for both groups (P = .045 and P = .006, respectively). However, the groups OB and
      IPB did not differ in respect to their fentanyl requirements (P = 1.000). Visual
      analog scores for pain were lowest in group IBP during the first 6 postoperative
      hours. The incidence of adverse effects was similar in all groups; serious
      adverse effects did not occur. CONCLUSIONS: According to the present study,
      intrabursal oxycodone and bupivacaine offer an acceptable and efficient method
      for postoperative analgesia after shoulder surgery.

PMID- 9773701
TI  - Comparison of intravenous nalbuphine infusion versus naloxone in the prevention
      of epidural morphine-related side effects.
AB  - BACKGROUND AND OBJECTIVES: Epidural morphine is accepted as an efficient means of
      postoperative pain management. However, development of side effects such as
      nausea and vomiting and pruritus has been reported. This study compared the
      efficacy of intravenous infusions of nalbuphine or naloxone in the prevention of
      epidural morphine-related side effects. METHODS: Seventy-five female patients
      undergoing epidural anesthesia for total hysterectomy were enrolled in a
      randomized, double-blind study. At the end of the surgery, all patients received
      epidural 3 mg morphine (every 12 hours) for postoperative pain. Meanwhile,
      patients in group 1 received an adjuvant intravenous infusion of nalbuphine 60
      microg/kg/h, patients in group 2 received intravenous infusion of naloxone 2
      microg/kg/h, and patients in group 3 received intravenous saline infusion only. A
      rescue analgesic of intramuscular 50 mg meperidine (every 4 hours) was available
      for each patient. Patients were observed for 24 hours. RESULTS: All patients had
      adequate postoperative pain relief. However, the proportion of patients requiring
      rescue analgesia and the total consumption of rescue analgesic were higher in
      group 2 than in the other two groups. The incidence of nausea and vomiting and
      pruritus was higher in group 3 than in the other two groups. CONCLUSIONS: We
      found that coadministration of either nalbuphine or naloxone with epidural
      morphine reduces the incidence of morphine-related side effects. However, unlike
      naloxone, nalbuphine did not attenuate the analgesic effect of epidural morphine.

PMID- 9773702
TI  - The influence of the menstrual cycle in postdural puncture headache.
AB  - BACKGROUND AND OBJECTIVES: We performed a preliminary study to analyze the
      influence of the menstrual cycle on the incidence of postdural puncture headache
      (PDPH). METHODS: One hundred sixty female patients with regular menstrual cycles
      who received spinal anesthesia were observed. Based on the day within the
      menstrual cycle that they received the puncture, the patients were classified
      into period A (perimenstrual) or period B (postmenstrual). The possible
      relationship among headaches, lifestyle habits, and anesthetic technique, and the
      presence of PDPH were analyzed, as were the levels of female sex hormones with
      PDPH in comparison with a control group. RESULTS: Seven cases of PDPH (4.3%) were
      observed--one within the perimenstrual group and six in the postmenstrual group.
      No significant differences were observed between the two periods or were there
      any differences in relating PDPH to the other variables analyzed. CONCLUSIONS:
      According to our results, the menstrual cycle and hormonal levels may not have
      any influence on the appearance of PDPH in female patients, although a larger
      series is required to validate these results.

PMID- 9773703
TI  - Infections from extended epidural catheterization in ambulatory patients.
AB  - BACKGROUND AND OBJECTIVES: Patients with severe and noncancer pain were treated
      with prolonged epidural infusions of analgesics in their homes, and the incidence
      of infection was determined. METHODS: In 504 adult patients, 3,164 polyamide
      lumbar epidural catheters were infused with analgesics of low-dose bupivacaine
      and fentanyl intermittently from 2 to 80 days at their home. When patients
      developed fever, headache, back pain, and leukocytosis, the presence of infection
      was confirmed by either computed tomographic scan, epidurogram, or sonogram.
      RESULTS: Nine infections (0.27%) occurred. Of these, two were epidural abscesses,
      two were fascitis, and five were cellulitis. Staphylococcus epidermidis was
      cultured in every case. All of them were treated with 1.5 g intravenous
      cefuroxime sodium every 8 hours. None of the patients required surgical
      intervention. In a subgroup of patients treated with the first 1,462 infused
      catheters, seven infections developed (0.4%), whereas in the subsequent 1,702
      cases that received prophylactic penicillin or erythromycin, in 6-day cycles,
      there were only two infections (0.11%). CONCLUSIONS: Temporary epidural infusions
      of analgesics up to 80 days are feasible in ambulatory patients with a low rate
      of infections. Preliminary observations appear to indicate that prophylactic
      antibiotics given intermittently further reduce the feasibility of infections.
      However, these observations may not apply to longer-lasting epidural infusions.

PMID- 9773704
TI  - Continuous sciatic nerve infusion: expanded case report describing a new
      approach.
AB  - BACKGROUND AND OBJECTIVES: Severe pain following extensive reconstructive foot
      surgery is difficult to manage effectively. Sciatic nerve block provides
      excellent analgesia for a limited duration. I wanted to determine an approach to
      sciatic nerve block enabling an infusion of a local anesthetic for a prolonged
      period without loss of efficacy due to catheter displacement. METHODS: Seventy
      six consecutive sciatic nerve catheter placements-in 73 patients undergoing
      reconstructive foot surgery-were performed by four different approaches. Soft
      epidural catheters were found to be unsatisfactory-both for placement and for
      prolonged infusion. A firmer catheter, also capable of "through the catheter"
      nerve stimulation, was developed and proved to be satisfactory on both counts.
      Traditional approaches proved satisfactory for identifying the nerve but were
      unsatisfactory for prolonged infusion. A unique "in line" approach was developed
      to enable the insertion of the catheter along the course of the sciatic nerve,
      thus maintaining position for prolonged infusions. RESULTS: According to
      predetermined criteria for success, only 64% of placements using traditional
      epidural catheters were successful, whereas the firmer catheter with "through the
      catheter" nerve stimulation was successful in 95% of placements. CONCLUSIONS: The
      described "in line" technique of continuous sciatic nerve infusion of a local
      anesthetic solution gives prolonged and effective analgesia following foot
      surgery.

PMID- 9773705
TI  - Eutectic mixture of local anesthetics in adult urology patients: an observational
      trial.
AB  - BACKGROUND AND OBJECTIVES: The effectiveness of EMLA eutectic mixture of local
      anesthetics, (ASTRA Co, France) cream in minor surgery on the penis and its
      acceptability in unpremedicated outpatients were assessed. METHODS: EMLA cream
      was applied 1 hour before surgery (fremulum plasty, circumcision or dorsal
      section for phimosis, and condyloma accuminatum) in addition to a subcutaneous
      infiltration of lidocaine 1%, just before incision in cases of circumcision.
      Verbal Rating Scale (VSR) was assessed during the surgery and the acceptance 15
      days later by a questionnaire. RESULTS: Thirty-two patients included. In all of
      the cases, the application of EMLA cream was sufficient, with the exception of
      one (fremulum plasty). General anesthesia was used for this patient unable to
      tolerate the proprioceptive sensations (VRS = 0). In cases of circumcision, the
      subcutaneous infiltration was not experienced as painful. Eighty-eight percent of
      patients who answered the questionnaire confirmed that if they had to be
      reoperated on, they would opt for this technique of anesthesia. CONCLUSION: EMLA
      cream is effective in minor penile surgery in adult patients, and it is
      associated with subcutaneous infiltration of local anesthetic in the case of
      circumcision.

PMID- 9773706
TI  - Spectral analysis of sudden bradycardia during intrathecal meperidine anesthesia.
AB  - BACKGROUND AND OBJECTIVES: Severe bradycardia occurring suddenly during spinal
      anesthesia, although rare, is potentially fatal. Bradycardias are more common
      after intrathecal meperidine. We report two such episodes occurring in elderly
      male patients undergoing transurethral surgery. METHODS: Subarachnoid block was
      provided using 50 mg meperidine. Autonomic function was assessed by measuring
      heart rate (HR) variability using R-R intervals from standard
      electrocardiographic recordings. Frequency-domain spectra were constructed from
      512 heartbeats, and an autoregressive method was used to calculate spectral
      power. RESULTS: In both patients, bradycardia (HR <50 beats/min) occurred after
      about 10 minutes and was associated with severe hypotension and a 10- to 100-fold
      increase in spectral density in both the low (0.04-0.15 Hz), mainly sympathetic,
      and the high (0.15-0.40 Hz), mainly parasympathetic, frequency bands. These
      spectral increases were subsequently attenuated by intravenous atropine. Heart
      rate slowing was noted to be periodic, or oscillatory, in one patient.
      CONCLUSION: Sudden increases in vagal, or parasympathetic, activity probably
      accounted for bradycardia.

PMID- 9773708
TI  - Delayed severe airway obstruction due to hematoma following stellate ganglion
      block.
AB  - BACKGROUND AND OBJECTIVES: Delayed onset of airway obstruction following stellate
      ganglion block (SGB) may be life threatening. We treated a patient who developed
      a severe airway obstruction caused by a large hematoma several hours after an
      SGB. METHODS: A 62-year-old woman suffering from sudden deafness developed
      dyspnea 2 hours after undergoing her fourth SGB, and evidenced swelling and
      tenderness in her anterior neck and chest. Her pharyngolaryngeal tissues were
      edematous, and the glottis was markedly narrowed. Computed tomograms and magnetic
      resonance images revealed a large soft tissue mass extending from the first
      cervical vertebra to the diaphragm. RESULTS: Surgical tracheotomy was performed
      to maintain her airway. Swelling of the vocal cord disappeared on the eleventh
      day after the operation. CONCLUSIONS: We believe that the SGB needle injured the
      vertebral artery and caused massive hemorrhage anterior to the cervical vertebra,
      subsequently inducing pharyngolaryngeal edema by obstructing the venous and
      lymphatic drainage of the cervical region.

PMID- 9773707
TI  - Repeated episodes of transient radiating back and leg pain following spinal
      anesthesia with 1.5% mepivacaine and 2% lidocaine.
AB  - BACKGROUND AND OBJECTIVES: Transient radiating back and leg pain defined as pain
      or dysesthesias in the buttocks, thighs, or calves within 24 to 48 hours after
      recovery from spinal anesthesia has been described with the use of 2% and 5%
      lidocaine. These symptoms have also been associated with other local anesthetics
      such as bupivacaine and tetracaine, although with a much lower incidence. A
      recent case report and prospective study have described transient radiating back
      and leg pain occurring following spinal anesthesia with 4% mepivacaine. METHODS:
      We describe a case of transient radiating back and leg pain following spinal
      anesthesia with 1.5% mepivacaine in a patient with unrecognized spinal stenosis
      who had had repeated episodes of transient radiating back and leg pain associated
      with lidocaine spinals. RESULTS: Spinal anesthesia with 1.5% mepivacaine was
      associated with transient radiating back and leg pain, which was similar in
      quality and duration to prior episodes following spinal anesthesia with
      lidocaine. CONCLUSIONS: Transient radiating back and leg pain may occur with
      lower concentrations (1.5%) of mepivacaine, as it does with lidocaine. The
      relationship between transient radiating back and leg pain and spinal stenosis is
      also discussed.

PMID- 9773709
TI  - Epidural insertion under general anesthesia.

PMID- 9773710
TI  - The combined spinal-epidural technique.

PMID- 9773711
TI  - Pericarditis following celiac plexus block.

PMID- 9773712
TI  - A proposed regional anesthesia motor scale (RAMS)

PMID- 9773713
TI  - Local anesthesia for preoperative and postoperative pain control in eye
      enucleation or evisceration: 20 cases.

PMID- 9773714
TI  - Do estrogens reduce glycemic levels?

PMID- 9773715
TI  - Metformin and lactic acidosis: guilt by association?

PMID- 9773716
TI  - Effect of postmenopausal hormone therapy on glucose and insulin concentrations.
      PEPI Investigators. Postmenopausal Estrogen/Progestin Interventions.
AB  - OBJECTIVE: To characterize the long-term impact of four hormone therapy regimens
      on insulin and glucose concentrations measured during a standard oral glucose
      tolerance test. RESEARCH DESIGN AND METHODS: The Postmenopausal
      Estrogen/Progestin Intervention Study was a 3-year placebo-controlled randomized
      trial to assess effects of four hormone regimens on cardiovascular risk factors.
      This efficacy analysis describes glucose and insulin concentrations from 788
      adherent women at baseline and at 1 and 3 years' postrandomization. RESULTS: When
      compared with women taking placebo, those taking conjugated equine estrogen (CEE)
      at 0.625 mg/day with or without a progestational agent had mean fasting insulin
      levels that were 16.1% lower, mean fasting glucose levels 2.2 mg/dl lower, and
      mean 2-h glucose levels 6.4 mg/dl higher (each nominal P < 0.05). No significant
      differences were apparent between women taking CEE only versus the three
      progestin regimens: medroxyprogesterone acetate (MPA) at 2.5 mg daily (continuous
      MPA), MPA at 10 mg on days 1-12 (cyclical MPA), and micronized progesterone (MP)
      (cyclical) at 200 mg on days 1-12. The impact of hormone therapy on insulin and
      glucose depended on baseline levels of fasting insulin and 1-h glucose (P <
      0.05). However, the treatment effects on carbohydrate metabolism appeared to be
      consistent across participant subgroups formed by lifestyle, clinical, and
      demographic characteristics. CONCLUSIONS: Oral hormone therapy involving 0.625
      mg/day of CEE may modestly decrease fasting levels of insulin and glucose.
      Postchallenge glucose concentrations are increased, however, which may indicate
      delayed glucose clearance.

PMID- 9773717
TI  - The Veterans Affairs Implantable Insulin Pump Study: effect on cardiovascular
      risk factors.
AB  - OBJECTIVE: To determine whether implantable insulin pump (IIP) and multiple-dose
      insulin (MDI) therapy have different effects on cardiovascular risk factors in
      insulin-requiring patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A
      randomized clinical trial was conducted at seven Veterans Affairs medical centers
      in 121 male patients with type 2 diabetes between the ages of 40 and 69 years
      receiving at least one injection of insulin per day and with HbA1c, levels of >
      or =8% at baseline. Weights, blood pressures, insulin use, and glucose monitoring
      data were obtained at each visit. Lipid levels were obtained at 0, 4, 8, and 12
      months, and free and total insulin levels were obtained at 0, 6, and 12 months.
      All medications being taken were recorded at each visit. RESULTS: No difference
      in absolute blood pressure, neither systolic nor diastolic, was seen between
      patients receiving MDI or IIP therapy, but significantly more MDI patients
      required anti-hypertensive medications. When blood pressure was modeled against
      weight and time, IIP therapy was significantly better than MDI therapy for
      systolic blood pressure in patients with BMI <33 and for diastolic blood pressure
      in patients with BMI >34 kg/m2. Total cholesterol levels decreased in the overall
      sample, but IIP patients exhibited significantly higher levels than MDI patients.
      Triglyceride levels increased over time for both groups, with IIP patients having
      significantly higher levels than patients in the MDI group. BMI was a significant
      predictor of, and inversely proportional to, HDL cholesterol level. No difference
      in lipid-lowering drug therapy was seen between the two groups. Free insulin and
      insulin antibodies tended to decrease in the IIP group as compared with the MDI
      group. C-peptide levels decreased in both groups. CONCLUSIONS: IIP therapy in
      insulin-requiring patients with type 2 diabetes has advantages over MDI therapy
      in decreasing the requirement for antihypertensive therapy and for decreasing
      total and free insulin and insulin antibodies. Both therapies reduce total
      cholesterol and C-peptide levels.

PMID- 9773718
TI  - Physical activity, dyspnea, and chest pain before and after coronary artery
      bypass grafting in relation to a history of diabetes.
AB  - OBJECTIVE: To describe the limitation of physical activity and symptoms of chest
      pain and dyspnea before and after coronary artery bypass grafting (CABG) in
      relation to a history of diabetes. RESEARCH DESIGN AND METHODS: All patients in
      western Sweden in whom CABG was performed between 1988 and 1991 were asked to
      complete a questionnaire before 3 months and 2 years after the operation. The
      questionnaire evaluated limitation of physical activity and symptoms of chest
      pain and dyspnea. RESULTS: In all, 2,121 patients participated in the evaluation,
      of whom 13% had a history of diabetes. The overall 2-year mortality was 14% among
      patients with a history of diabetes and 6% among patients without such a history
      (P < 0.001). The proportion of patients with a limitation of physical activity
      caused by chest pain decreased from 76% before CABG to 19% 2 years after in
      diabetic patients (P < 0.001) and from 79 to 17% in nondiabetic patients (P <
      0.001). The proportion of diabetic patients without dyspnea increased from 13%
      before to 31% 2 years after CABG (P < 0.001). The corresponding figures for
      nondiabetic patients were 12 and 43% (P < 0.001). Symptoms of angina pectoris
      were reported in 94% of diabetic patients before CABG versus 35% after 2 years (P
      < 0.001). Corresponding figures for nondiabetic patients were 93 and 29% (P <
      0.001). Aggregate data confirmed differences between diabetic and nondiabetic
      patients, with more symptoms in the diabetic patients, particularly with regard
      to dyspnea. CONCLUSIONS: Mortality during 2 years of follow up was more than
      twice as high in diabetic than in nondiabetic patients. Limitation of physical
      activity, dyspnea, and angina pectoris improved markedly and similarly in
      diabetic and nondiabetic patients after CABG. Whereas limitation of physical
      activity and dyspnea was more frequent in diabetic than in nondiabetic patients,
      the occurrence of angina pectoris was more similar in the two groups.

PMID- 9773719
TI  - No relationship between carbohydrate intake and effect of acarbose on HbA1c or
      gastrointestinal symptoms in type 2 diabetic subjects consuming 30-60% of energy
      from carbohydrate.
AB  - OBJECTIVE: To determine the relationship between carbohydrate intake and the
      effect of acarbose on HbA1c in subjects with type 2 diabetes treated with
      acarbose alone, acarbose plus sulfonylurea, acarbose plus metformin, or acarbose
      plus insulin. RESEARCH DESIGN AND METHODS: We conducted a double-blind randomized
      placebo-controlled study in which subjects with diabetes in four treatment strata
      (77 on diet alone, 83 treated with metformin, 103 treated with sulfonylurea, and
      91 treated with insulin) were randomized to treatment with placebo or acarbose
      for 12 months. Before randomization, and 3, 6, 9, and 12 months after
      randomization, fasting blood was obtained for HbA1c, and 3-day diet records were
      collected. Subjects who completed at least 6 months of acarbose therapy and
      provided at least three 3-day diet records were included. RESULTS: In the 114
      subjects included in this analysis, carbohydrate intake varied from approximately
      30-60% of energy There was no significant relationship between carbohydrate
      intake and change in HbA1c in any of the four treatment strata (diet: n=26,
      r=0.35, P=0.076; metformin: n=27, r=0.26, P=0.19; sulfonylurea: n=35, r=0.24,
      P=0.16; insulin: n=25, r=-0.27, P=0.19). In the 80 subjects consuming <50% of
      energy from carbohydrate, the fall in HbA1c (7.83 +/-0.17% at baseline to 6.72+/
      0.13% on acarbose, P < 0.001) was no different from that of the 34 subjects
      consuming >50% of energy from carbohydrate (7.55+/-0.25% at baseline to 6.66+/
      0.23% on acarbose, P < 0.001). There was no difference in carbohydrate intake
      between those who dropped out of the study because of gastrointestinal side
      effects and those who did not, and there was no relationship between severity of
      symptoms and the composition of the diet. CONCLUSIONS: In subjects with type 2
      diabetes consuming 30-60% of energy from carbohydrate, the effect of acarbose on
      HbA1c and gastrointestinal symptoms was not related to carbohydrate intake.
      Because most people consume at least 30% of energy from carbohydrate, we conclude
      that no special diet is needed for acarbose to be effective in improving blood
      glucose control in the treatment of type 2 diabetes.

PMID- 9773720
TI  - Acute metabolic response to high-carbohydrate, high-starch meals compared with
      moderate-carbohydrate, low-starch meals in subjects with type 2 diabetes.
AB  - OBJECTIVE: The monosaccharides resulting from the digestion of ingested
      carbohydrates are glucose, fructose, and galactose. Of these three
      monosaccharides, only ingested glucose resulted in a large increase in the plasma
      glucose concentration. Fructose (Metabolism 41:510-517, 1992) and galactose
      (Metabolism 42:1560-1567, 1993) had only a minor effect. Therefore, we were
      interested in determining whether we could design a mixed meal, using foods of
      known monosaccharide, disaccharide, and starch composition, the ingestion of
      which would result in only a small rise in plasma glucose concentration. RESEARCH
      DESIGN AND METHODS: The experimental meal was composed of very little readily
      digestible starch but rather large amounts of fruits and vegetables. It contained
      43% carbohydrate, 22% protein, and 34% fat. The results were compared with a
      second type of meal that contained 55% carbohydrate, 15% protein, and 30% fat,
      with an emphasis on complex carbohydrates (starch). It also was compared with a
      third meal that contained 40% carbohydrate, 20% protein, and 40% fat, typical of
      that consumed by the average American. The test meals were ingested in random
      order by people with type 2 diabetes who were not treated with oral hypoglycemic
      agents or insulin. Each subject ingested each type of meal. The same identical
      meal was ingested at 0800, 1200, and 1700. RESULTS: The integrated 24-h plasma
      glucose area response was statistically significantly smaller (P < 0.05) after
      ingestion of the low-starch meals compared with the high-starch, high
      carbohydrate meals or the typical American meals. The 24-h integrated serum
      insulin area response also was statistically significantly less (P < 0.05) after
      ingestion of the low-starch meals compared with the high-starch meals or the
      typical American meals. The serum triglyceride area response was similar after
      ingestion of all three test diets. CONCLUSIONS: A diet in which fruits, nonstarch
      vegetables, and dairy products are emphasized may be useful for people with type
      2 diabetes.

PMID- 9773721
TI  - Effect of continuous subcutaneous insulin infusion with lispro on hepatic
      responsiveness to glucagon in type 1 diabetes.
AB  - OBJECTIVE: People with type 1 diabetes frequently develop a blunted
      counterregulatory hormone response to hypoglycemia coupled with a decreased
      hepatic response to glucagon, and consequently, they have an increased risk of
      severe hypoglycemia. We have evaluated the effect of insulin lispro (Humalog)
      versus regular human insulin (Humulin R) on the hepatic glucose production (HGP)
      response to glucagon in type 1 diabetic patients on intensive insulin therapy
      with continuous subcutaneous insulin infusion (CSII). RESEARCH DESIGN AND
      METHODS: Ten subjects on CSII were treated for 3 months with lispro and 3 months
      with regular insulin in a double-blind randomized crossover study After 3 months
      of treatment with each insulin, hepatic sensitivity to glucagon was measured in
      each subject. The test consisted of a 4-h simultaneous infusion of somatostatin
      (450 microg/h) to suppress endogenous glucagon, regular insulin (0.15 mU x kg(-1)
      x min(-1)), glucose at a variable rate to maintain plasma glucose near 5 mmol/l,
      and D-[6,6-2H2]glucose to measure HGP During the last 2 h, glucagon was infused
      at 1.5 ng x kg(-1) x min(-1). Eight nondiabetic people served as control
      subjects. RESULTS: During the glucagon infusion period, free plasma insulin
      levels in the diabetic subjects were 71.7+/-1.6 vs. 74.8+/-0.5 pmol/l after
      lispro and regular insulin treatment, with plasma glucagon levels of 88.3+/-1.8
      and 83.7+/-1.5 ng/l for insulin:glucagon ratios of 2.8 and 3.0. respectively
      (NS). However, plasma glucose increased to 9.2+/-1.1 mmo/l after lispro insulin
      compared with 7.1+/-0.9 mmol/l after regular insulin (P < 0.01), and the rise in
      HGP was 5.7 +/-2.8 micromol x kg(-1) x min(-1) after lispro insulin versus 3.1+/
      2.9 micromol x kg(-1) x min(-1) after regular insulin treatment (P=0.02). In the
      control subjects, HGP increased by 10.7+/-4.2 micromol x kg(-1) x min(-1) under
      glucagon infusion. CONCLUSIONS: Insulin lispro treatment by CSII was associated
      with a heightened response in HGP to glucagon compared with regular human
      insulin. This suggests that insulin lispro increases the sensitivity of the liver
      to glucagon and could potentially decrease the risk of severe hypoglycemia.

PMID- 9773722
TI  - Descriptive epidemiology of IDDM in Hokkaido, Japan: the Childhood IDDM Hokkaido
      Registry.
AB  - OBJECTIVE: To identify the incidence of IDDM with regard to sex, age, family
      history of diabetes, season, and 5-year period of childhood IDDM among children
      ages 0-14 years from a population-based epidemiological study in Hokkaido, Japan,
      from 1973 to 1992. RESEARCH DESIGN AND METHODS: Registration of all new IDDM
      cases in Hokkaido was conducted by the Childhood IDDM Hokkaido Registry Study
      Group from 1973 to 1992. The cases were selected from among 1) patients who were
      admitted to the member hospitals of the study group, 2) patients who answered a
      questionnaire distributed to hospitals and diabetic clinics throughout Hokkaido,
      and 3) patients whose cases were recorded in free-treatment medical records of
      urban and rural districts. The case ascertainment rate was estimated to be 100%.
      Differences in incidence with regard to sex, age, family history of diabetes,
      season, and year period were analyzed by the Poisson regression analysis by
      GENMOD. RESULTS: During the 20-year period studied, 396 cases (181 boys, 215
      girls) of abrupt-onset IDDM were registered. Statistically significant
      differences in annual incidence were found according to sex (female), age (8-14
      years), history (having no diabetes in family), season (spring), and 5-year
      period. CONCLUSIONS: This is the first population-based, long-term
      epidemiological study of childhood IDDM from Japan. We observed a significantly
      higher annual incidence (per 100,000/year) of IDDM in female subjects (1.81),
      older age-groups (2.25 for 8-14 years), subjects with no family history of
      diabetes (1.26), diabetes onset in the spring (2.20), and an increased trend over
      the 20 years. In addition, the heterogeneity of IDDM among Japanese children
      needs to be elucidated.

PMID- 9773723
TI  - Weight gain and the risk of developing insulin resistance syndrome.
AB  - OBJECTIVE: Obesity and weight gain have been associated independently with
      hypertension, hyperinsulinemia, and dyslipidemia; however, prior research has not
      looked at the relation between weight gain from early adulthood to middle age and
      the development of this cluster of risk factors, known as insulin resistance
      syndrome. RESEARCH DESIGN AND METHODS: The association between weight gain over
      30 years (defined as the difference between measured weight in middle age and
      participant recall of their weight at age 20) and the odds of developing insulin
      resistance syndrome at middle age was examined in a population-based sample of
      2,272 eastern Finnish men. RESULTS: Each 5% increase in weight over the reported
      weight at age 20 was associated with nearly a 20% greater risk of insulin
      resistance syndrome by middle age, after adjustment for age and height. Moreover,
      there was a strong graded association between categories of weight gain and risk
      of insulin resistance syndrome. Men with weight increases of 10-19%, 20-29%, or >
      or =30% since age 20 were 3.0, 4.7, or 10.6 times more likely to have insulin
      resistance syndrome, respectively, by middle age, compared with men within 10% of
      their weight at age 20. Adjustments for age, height, physical activity, smoking,
      education, and parental history of diabetes did not alter these findings.
      CONCLUSIONS: The odds of having developed the hemodynamic and metabolic
      abnormalities that characterize insulin resistance syndrome by middle adulthood
      were increasingly higher the greater the weight gain over the preceding 30 years.
      This study adds to the literature identifying deleterious effects of weight gain
      from young to middle adulthood.

PMID- 9773724
TI  - Supporting autonomy to motivate patients with diabetes for glucose control.
AB  - OBJECTIVE: We applied the self-determination theory of human motivation to
      examine whether patient perceptions of autonomy supportiveness (i.e., patient
      centeredness) from their diabetes care providers related to improved glucose
      control over a 12-month period. RESEARCH DESIGN AND METHODS: We conducted a
      prospective cohort study of patients with diabetes from a diabetes treatment
      center at a university-affiliated community hospital. Participants were 128
      patients between 18 and 80 years of age who took medication for diabetes, had no
      other major medical illnesses, and were responsible for monitoring their glucose
      and taking their medications. The main outcome measure was a change in HbA1c
      values over the 12 months of the study RESULTS: Patient perception of autonomy
      support from a health care provider related to a change in HbA1c values at 12
      months (P < 0.05). Further analyses showed that perceived autonomy support from
      the staff related to significant increases in patient autonomous motivation at 12
      months (P < 0.05); that increases in autonomous motivation related to significant
      increases in perceived competence (P < 0.05); and that increases in a patient's
      perceived competence related to significant reductions in their HbA1c values over
      12 months (P < 0.001). CONCLUSIONS: The findings support the prediction of the
      self-determination theory that patients with diabetes whose health care providers
      are autonomy supportive will become more motivated to regulate their glucose
      levels, feel more able to regulate their glucose, and show improvements in their
      HbA1c values.

PMID- 9773726
TI  - Lactic acidosis rates in type 2 diabetes.
AB  - OBJECTIVE: To provide a context for the interpretation of lactic acidosis risk
      among patients using metformin, we measured rates of lactic acidosis in patients
      with type 2 diabetes before metformin was approved for use in the U.S. RESEARCH
      DESIGN AND METHODS: Using electronic databases of hospital discharge diagnoses
      and laboratory results maintained by a large, nonprofit health maintenance
      organization (HMO). we identified possible lactic acidosis events in three
      geographically and racially diverse populations with type 2 diabetes. We then
      reviewed hard-copy clinical records to confirm and describe each event and
      determine its likely cause(s). RESULTS: From >41.000 person-years of experience,
      we found four confirmed, three possible, and three borderline cases of lactic
      acidosis. In each case, we identified at least one severe medical condition that
      could have caused the acidosis. The annual confirmed event rate is similar to
      published rates of metformin-associated lactic acidosis. CONCLUSIONS: Lactic
      acidosis occurs regularly, although infrequently, among persons with type 2
      diabetes, at rates similar to its occurrence among metformin users. The medical
      conditions with which both metformin-associated and naturally occurring lactic
      acidosis co-occur are also its potential causes. The observed association between
      metformin and lactic acidosis may be coincidental rather than causal. This
      possibility merits further study

PMID- 9773725
TI  - Birth weight, adult weight, and girth as predictors of the metabolic syndrome in
      postmenopausal women: the Rancho Bernardo Study.
AB  - OBJECTIVE: Recent studies have demonstrated an association between low birth
      weight and chronic and metabolic disorders in adulthood such as type 2 diabetes,
      hypertension, and dyslipidemia. These disorders tend to cluster in a condition
      known as the metabolic syndrome (syndrome X). Only two studies have reported an
      association of birth weight to the metabolic syndrome. The present study is
      distinguished as the only study to focus on postmenopausal women. RESEARCH DESIGN
      AND METHODS: Subjects were 303 community-dwelling, postmenopausal Caucasian women
      aged 50-84 years. Metabolic and anthropometric variables were measured at a
      clinic visit; birth weight was assessed by self-report on a mailed questionnaire.
      RESULTS: The metabolic syndrome, defined as the simultaneous presence of
      hypertension, dyslipidemia, and abnormal glucose tolerance, was present in 7.9%
      of these women. Compared with women in the highest birth weight tertile (8.1-13.0
      lb, mean 9.4 lb), those in the lowest birth weight tertile (2.5-6.8 lb, mean 5.5
      lb) exhibited an increased prevalence (12.0 vs. 4.3%, P < 0.05) and 2.41 times
      the risk (95% CI 1.06-5.51) of developing the metabolic syndrome. Women with a
      heavy birth weight had an increased risk of adult obesity. Nevertheless, women in
      the lowest birth weight tertile who became adults in the highest tertile of BMI
      (>25.2 kg/m2) or waist circumference (>80.7 cm) had the highest prevalence of the
      metabolic syndrome (approximately 30%). CONCLUSIONS: Low birth weight coupled
      with adult obesity is a strong determinant of the metabolic syndrome in
      postmenopausal women.

PMID- 9773727
TI  - Prevalence of retinopathy in people with diabetes, impaired glucose tolerance,
      and normal glucose tolerance.
AB  - OBJECTIVE: Recently, an international expert committee published new revised
      criteria for diagnosing diabetes. According to the new criteria, the 2-h glucose
      level for diabetes in the oral glucose tolerance test (OGTT) is the same as in
      the previous World Health Organization criteria, but the cut point for the
      fasting blood glucose level has been lowered to be equivalent to the 2-h OGTT
      level. Measurement of the fasting blood glucose level is preferred to the 2-h
      OGTT glucose level. The ability of the new cut point for fasting blood glucose to
      discriminate between those at a high and a low risk for retinopathy was tested in
      a population-based study RESEARCH DESIGN AND METHODS: The population consisted of
      all the 1,008 subjects (456 men) born in 1935 and living in a Finnish city A
      screening for type 2 diabetes was carried out in the first phase. All
      participants who were not on antidiabetic medication were invited for an OGTT in
      the second phase. A fasting blood glucose value was measured from the diabetic
      subjects on antidiabetic medication. In addition, measurements of serum
      cholesterol, HDL cholesterol, and triglycerides were made, and fundus photographs
      were taken. Altogether, 831 subjects (368 men) (82%) participated and constitute
      the eligible study population for the present analyses. Fundus photographs were
      available for 790 subjects (347 men) (95%). RESULTS: There were 28 subjects
      (3.5%) who had mild retinopathic changes in the fundus photographs. Retinopathic
      changes were associated with higher fasting blood glucose levels, but not with
      any of the other background factors. The prevalence of retinopathy was 10.2% (95%
      CI 4.8-18.5) in subjects with a fasting blood glucose of > or =6.1 mmol/l, while
      it was 2.6% (1.5-4.0) in those with a lower fasting blood glucose level. In the
      former group, a majority (seven of nine) of the subjects with retinopathy were
      previously diagnosed diabetic patients. Some cases of retinopathy were found
      regardless the level of glycemia, and measurement of the 2-h OGTT glucose levels
      did not increase information. CONCLUSIONS: The results of this population study
      give support to the use of fasting blood glucose levels in diagnosing type 2
      diabetes. The lower limit of the highest decile of the fasting glucose level was
      6.1 mmol/l, and it discriminated subjects at a high risk for retinopathy from
      those at a low risk. Because of the limited number of subjects with retinopathy
      in this study, the level of hyperglycemia associated with retinopathy cannot be
      estimated accurately.

PMID- 9773728
TI  - Islet cell antibodies are less predictive of IDDM among unaffected children in
      the general population than in sibs of children with diabetes. The Childhood
      Diabetes in Finland Study Group.
AB  - OBJECTIVE: To examine the controversial issue of whether islet cell antibodies
      (ICAs) have a higher predictive value for progression to clinical IDDM in first
      degree relatives of patients with diabetes than in the general population.
      RESEARCH DESIGN AND METHODS: ICAs were analyzed with standard immunofluorescence
      in two population-based groups: 765 sibs of children with recent-onset diabetes
      and 1,212 unaffected Finnish children <20 years of age at initial screening.
      Those positive for ICAs were additionally tested for antibodies to GAD (GADAs)
      and the protein tyrosine phosphatase-related IA-2 antigen (IA-2As). Subsequently,
      these subjects were observed for the manifestation of clinical IDDM over the next
      7 years. RESULTS: The frequency of both detectable ICAs and ICA levels > or =20
      Juvenile Diabetes Foundation units (JDF U) was significantly higher among the
      sibs than in the general population (7.8 vs. 4.1% and 4.8 vs. 2.0%, respectively;
      P < 0.001). The prevalence of GADAs (37/60 vs. 3/48; P < 0.001) and IA-2As (31/60
      vs. 0/48; P < 0.001) was increased among ICA-positive sibs compared with ICA
      positive individuals from the background population. Over the next 7 years, 24
      sibs (3.1%) and 3 unrelated children positive for ICAs (0.3%) progressed to
      clinical diabetes. The positive predictive value of ICAs was thus 6% in the
      general population and 40% among the sibs (P < 0.001), or 13 and 59%,
      respectively (P < 0.001), with an antibody cutoff level of 20 JDF U. The positive
      predictive value was related to the number of positive autoantibodies in sibs,
      which was 57% in those with three antibodies, 50% in those with two antibodies,
      and only 6% in those with ICAs alone. CONCLUSIONS: These data show that the
      frequency of multiple autoantibodies is substantially lower in ICA-positive
      children representing the general population than in ICA-positive sibs of
      children with IDDM. As a consequence, the predictive value of ICAs for IDDM is
      higher in sibs of affected children than in the general population. This finding
      must be taken into account when planning intervention trials aimed at preventing
      or delaying the manifestation of clinical diabetes in individuals from the
      general population who test positive for ICAs.

PMID- 9773729
TI  - Puberty, IDDM, and death in Japan. Diabetes Epidemiology Research International
      Study Group.
AB  - OBJECTIVE: To investigate the impact of age at onset on the prognosis of
      childhood IDDM in Japan. RESEARCH DESIGN AND METHODS: The study population
      consisted of 987 prepubertal-onset and 345 pubertal-onset IDDM cases who were
      registered by two nationwide surveys and who were diagnosed between 1965 and
      1979. The living status was identified as of 1 January 1990 with the
      ascertainment rate of 96.5%. Prognosis was evaluated by cause- and age-specific
      mortality rates and life-table analyses; in addition, an attained-age-matched
      case-control study was analyzed by conditional logistic regression. RESULTS: The
      adjusted mortality rates per 100,000 person-years for the pubertal-onset cases
      were significantly higher than those of the prepubertal-onset cases (835 [95% CI
      573-1,168] vs. 391 [283-526]). Life-table analyses revealed that the survival
      rate of the pubertal-onset cases was lower than that of the prepubertal-onset
      cases for each observation period. Life-table analyses after the age of 15 years
      indicated that the prognosis of pubertal cases was almost the same as that of the
      prepubertal cases despite having a shorter duration of diabetes. The attained-age
      matched case-control study indicated that the pubertal onset was a potent
      determinant of death. CONCLUSIONS: The prognosis of pubertal-onset IDDM was
      considerably poorer than that of prepubertal-onset IDDM.

PMID- 9773730
TI  - Is type 2 diabetes a different disease in obese and nonobese patients?
AB  - OBJECTIVE: The main purpose of this work was to study the possible differences in
      insulin secretion in a large group of type 2 diabetic patients in relation to
      diabetes duration, obesity, and the presence of secondary failure after treatment
      with oral hypoglycemic agents. RESEARCH DESIGN AND METHODS: There were 147
      nonobese and 215 obese type 2 diabetic subjects, aged 35-80 years, investigated
      in a cross-sectional descriptive study Subjects were grouped according to whether
      glycemic control was good (mean blood glucose <8.5 mmol/l) or poor. Beta-cell
      function was assessed by measuring meal-stimulated insulin and C-peptide
      concentrations, as the mean of the three postprandial increments above the
      premeal value. RESULTS: Basal C-peptide concentrations were significantly higher
      in obese than nonobese patients of both groups. The mean of meal-stimulated C
      peptide concentrations was also significantly higher in obese than nonobese
      patients with good glycemic control, but not in the secondary failure groups. In
      nonobese and obese patients considered separately, a significant negative
      correlation between the mean of daily blood glucose and meal-stimulated C-peptide
      was observed (r=-0.705 and r=-0.679, respectively, P < 0.001) and the residual
      beta-cell function was significantly correlated with the known duration of
      diabetes and metabolic control, but not with BMI, in both groups. CONCLUSIONS: On
      average, obese diabetic subjects showed higher meal-stimulated C-peptide than
      nonobese subjects only in well-controlled groups. In both obese and nonobese
      patients, an inverse association between meal-stimulated insulin secretion and
      duration of diabetes was observed. In obese patients, as in nonobese patients,
      the lower beta-cell function seems likely to be the major pathogenetic factor in
      the appearance of secondary failure, while being overweight plays only a minor
      role, thus showing that type 2 diabetes is the same disease in obese and nonobese
      patients.

PMID- 9773731
TI  - The 1997 American Diabetes Association criteria versus the 1985 World Health
      Organization criteria for the diagnosis of abnormal glucose tolerance: poor
      agreement in the Hoorn Study.
AB  - OBJECTIVE: Recently, the American Diabetes Association (ADA) introduced new
      diagnostic criteria. These new criteria are based on fasting plasma glucose
      levels, avoiding the burdensome oral glucose tolerance test (OGTT). We compared
      the 1997 ADA criteria with the 1985 World Health Organization (WHO) criteria with
      respect to the prevalence of diabetes and the cardiovascular risk profile in the
      population of the Hoorn Study RESEARCH DESIGN AND METHODS: The Hoorn Study is a
      population-based survey of 2,484 men and women, aged 50-75 years. An OGTT was
      performed and cardiovascular risk factors were determined in 2,378 subjects
      without known diabetes. Subjects were categorized according to both sets of
      diagnostic criteria. RESULTS: Although the prevalence of diabetes was similar for
      both sets of criteria, 47 of 120 (39.2%) subjects who were diagnosed with
      diabetes according to the 1997 ADA criteria were not classified as having
      diabetes when using the 1985 WHO criteria. Similarly, of 285 subjects diagnosed
      with impaired fasting glucose by the 1997 ADA criteria, 195 (68.4%) were
      classified as having normal glucose tolerance by the 1985 WHO criteria. The
      overall agreement was poor (kappa 0.33; 95% CI 0.28-0.38). Subjects who were
      diagnosed as having diabetes by either set of criteria had an adverse
      cardiovascular risk profile, which was between the cardiovascular risk profiles
      of concordant normal and concordant diabetic subjects. CONCLUSIONS: In this study
      both sets of criteria diagnosed a similar number of diabetic subjects, but many
      of the subjects shifted between glucose intolerance categories. With either set
      of criteria, a considerable number of subjects at risk of developing diabetes and
      subjects carrying an increased risk of cardiovascular disease, as reflected by an
      adverse cardiovascular risk profile, will be missed.

PMID- 9773732
TI  - Effect of bacille Calmette-Guerin vaccination on C-peptide secretion in children
      newly diagnosed with IDDM.
AB  - OBJECTIVE: To determine whether administration of bacille Calmette-Guerin (BCG)
      vaccination to newly diagnosed IDDM patients can help preserve C-peptide
      secretion over the subsequent 18 months. RESEARCH DESIGN AND METHODS: Twenty-six
      IDDM patients, all of whom had been diagnosed within the previous year, had basal
      C-peptide levels >0.06 nmol/l, and had negative reactions to Mantoux's test, were
      randomized pairwise as they presented and were given either 0.1 ml (100 microg)
      BCG vaccine or 0.1 ml saline intradermally Both the patients and the
      investigators were blinded to the treatment. Fasting and glucagon-induced C
      peptide levels and HbA1c were measured in all patients at enrollment and at 1, 3,
      6, 9, 12, and 18 months after vaccination, and insulin dose was recorded at each
      visit. RESULTS: At enrollment, there was no significant difference in age,
      duration of diabetes, insulin dose, HbA1c, or fasting C-peptide levels between
      the BCG-vaccinated and control groups. The mean basal and stimulated C-peptide
      levels in the BCG-treated group did not differ significantly from those in the
      control group at any time during the 18 months of follow-up, and there was no
      difference in insulin dose or HbA1c at any time between the groups. CONCLUSIONS:
      BCG vaccination in children who have been recently diagnosed with IDDM does not
      affect the progressive decline in C-peptide levels or alter the clinical course
      of the disease.

PMID- 9773733
TI  - Improved glycemic control in intensively treated type 1 diabetic patients using
      blood glucose meters with storage capability and computer-assisted analyses.
AB  - OBJECTIVE: To determine the effect on glycemic control in intensively treated
      type 1 diabetic patients using a blood glucose meter with storage capability and
      computer-assisted analyses. RESEARCH DESIGN AND METHODS: Glycemic control was
      assessed in 22 intensively treated adults with type 1 diabetes for 12 months
      while using a meter without memory, followed by 12 months while using a meter
      with memory. Log books were used to assist patients in managing aspects of the
      diabetes treatment plan during the first 12-month period, and computer-assisted
      analyses were used when the meter with memory was used. GHb levels were measured
      monthly throughout the 24 months of observation. RESULTS: The mean GHb level
      averaged across all patients during the period of memory meter use (6.4%) was
      significantly lower than that during the period of meter use without memory
      (6.9%) (P=0.0004). The change in GHb levels from each period-specific baseline
      level occurred at significantly different slopes (P=0.046) when adjusted for
      baseline GHb level. In addition, the downward trend in GHb level was greater in
      those patients who increased the frequency of testing the most (r=-0.54, P=0.01).
      CONCLUSIONS: Use of a meter with memory in conjunction with computer-generated
      analyses of stored blood glucose test results can lead to improved glycemic
      control when used by a group of intensively treated adult diabetic patients.
      Improvement in glycemic control was related to frequency of blood glucose
      testing.

PMID- 9773734
TI  - Effect of domperidone on the health-related quality of life of patients with
      symptoms of diabetic gastroparesis.
AB  - OBJECTIVE: To describe the health-related quality of life (HRQOL) of patients
      with insulin-treated diabetes and symptoms of diabetic gastroparesis and to
      assess the impact of domperidone on HRQOL in these patients. RESEARCH DESIGN AND
      METHODS: This two-phase multicenter study was part of a safety and efficacy
      investigation. Phase I involved 4-week single-blind treatment with domperidone 20
      mg q.i.d. (n=269). Patients demonstrating significant symptomatic improvement
      (n=208) continued to phase 11, a 4-week, double-blind, parallel-group study with
      patients receiving placebo (n=103) or domperidone (n=105). Patients completed the
      Medical Outcomes Study Short-Form-36 Health Survey at selection and at the end of
      each phase. Physical component summary (PCS) and mental component summary (MCS)
      scores served as primary parameters, and the eight subscales were secondary
      parameters. RESULTS: HRQOL scores of subjects enrolled in the trial were
      significantly lower than norms from the general population and people with
      diabetes (P < 0.001). Subjects experiencing symptomatic improvement after 4 weeks
      of single-blind treatment demonstrated significant improvement in all HRQOL
      parameters (P < 0.001); PCS, MCS, and six subscale scores of nonresponders did
      not change. Between-group change score differences were significant for PCS, MCS,
      and seven subscales (P < 0.05 to P < 0.001). During phase II, the domperidone
      group maintained their HRQOL; the placebo group showed a significant decline in
      PCS and four subscales (P < 0.05). The between-group difference in the PCS score
      change was statistically significant (-1.77 vs. 0.65, P=0.05). CONCLUSIONS:
      Results suggest that patients with symptoms of diabetic gastroparesis experience
      notable HRQOL impairment and that symptomatic relief with domperidone is
      accompanied by improvements in HRQOL that can be sustained over 4 weeks of
      treatment.

PMID- 9773735
TI  - Optimal provision of daytime NPH insulin in patients using the insulin analog
      lispro.
AB  - OBJECTIVE: Insulin lispro improves early postprandial blood glucose control but
      can result in late interprandial hyperglycemia. As an approach to resolving this
      problem, we performed a randomized, crossover study with four treatment arms,
      comparing the daytime metabolic profile after either premeal lispro alone or
      premeal lispro with optimal daytime NPH insulin and with standard human regular
      insulin. RESEARCH DESIGN AND METHODS: Twelve C-peptide negative type 1 diabetic
      patients were studied on four separate study days, at least 7 days apart. On each
      study day, patients received one of the four study insulin treatments, in random
      order, with identical meals and snacks. The four treatments were 1) premeal human
      regular insulin before lunch and supper at unchanged dose; 2) premeal lispro
      (unchanged dose) at lunchtime and dinner; 3) pre-lunch reduced-dose lispro (70%)
      before lunch and supper with supplemental lunchtime NPH and with a 6-h interval
      until dinner; and 4) pre-lunch reduced-dose lispro (70%) before lunch and supper
      with supplemental lunchtime NPH and with a 8-h interval until dinner. All
      patients were using their usual premeal plus basal insulin regimen during the
      period of the study, with human regular insulin before meals and NPH insulin at
      bedtime. RESULTS: Postprandial blood glucose concentrations (1230-1500) were
      lower after reduced or usual lispro dose compared with human regular insulin
      (5.5+/-0.2 and 5.6+/-0.2 vs. 8.2+/-0.5 mmol/l, P < 0.001), with no difference
      between the lispro doses. However, prepran-Dial (1800) blood glucose levels
      deteriorated to higher levels after usual-dose lispro alone compared with either
      human regular insulin (P < 0.05) or reduced-dose lispro plus NPH (P < 0.05)
      (8.9+/-0.3 vs. 7.1+/-0.8 and 6.4+/-0.4 mmol/l), with no difference between human
      regular insulin and reduced-dose lispro plus NPH. During the 2 h between the
      usual and delayed mealtime, blood glucose concentrations remained controlled on
      lispro plus NPH (2000: 6.5+/-0.4 mmol/l). CONCLUSIONS: Reduced-dose lunchtime
      lispro plus NPH maintained the improvement in postprandial blood glucose control
      with no deterioration in interprandial blood glucose control, even up to a late
      meal.

PMID- 9773736
TI  - Role of neuropathy and high foot pressures in diabetic foot ulceration.
AB  - OBJECTIVE: High plantar foot pressures in association with peripheral neuropathy
      have been ascertained to be important risk factors for ulceration in the diabetic
      foot. Most studies investigating these parameters have been limited by their size
      and the homogeneity of study subjects. The objective of this study was therefore
      to ascertain the risk of ulceration associated with high foot pressures and
      peripheral neuropathy in a large and diverse diabetic population. RESEARCH DESIGN
      AND METHODS: We studied a cross-sectional group of 251 diabetic patients of
      Caucasian (group C) (n=121), black (group B) (n=36), and Hispanic (group H)
      (n=94) racial origins with an overall age of 58.5+/-12.5 years (range 20-83).
      There was an equal distribution of men and women across the entire study
      population. All patients underwent a complete medical history and lower extremity
      evaluation for neuropathy and foot pressures. Neuropathic parameters were
      dichotomized (0/1) into two high-risk variables: patients with a vibration
      perception threshold (VPT) > or =25 V were categorized as HiVPT (n=132) and those
      with Semmes-Weinstein monofilament tests > or =5.07 were classified as HiSWF
      (n=190). The mean dynamic foot pressures of three footsteps were measured using
      the F-scan mat system with patients walking without shoes. Maximum plantar
      pressures were dichotomized into a high-pressure variable (Pmax6) indicating
      those subjects with pressures > or =6 kg/cm2 (n=96). A total of 99 patients had a
      current or prior history of ulceration at baseline. RESULTS: Joint mobility was
      significantly greater in the Hispanic cohort compared with the other groups at
      the first metatarsal-phalangeal joint (C 67+/-23 degrees, B 69+/-23 degrees, H
      82+/-23 degrees, P=0.000), while the subtalar joint mobility was reduced in the
      Caucasian group (C 21+/-8 degrees, B 26+/-7 degrees, H 27+/-11 degrees, P=0.000).
      Maximum plantar foot pressures were significantly higher in the Caucasian group
      (C 6.7+/-2.9 kg/cm2, B 5.7+/-2.8 kg/cm2, H 4.4+/-1.9 kg/cm2, P=0.000). Univariate
      logistic regression for Pmax6 on the history of ulceration yielded an odds ratio
      (OR) of 3.9 (P=0.000). For HiVPT, the OR was 11.7 (P=0.000), and for HiSWF the OR
      was 9.6 (P=0.000). Controlling for age, diabetes duration, sex, and race (all P <
      0.05), multivariate logistic regression yielded the following significant
      associations with ulceration: Pmax6 (OR=2.1, P=0.002), HiVPT (OR=4.4, P=0.000),
      and HiSWF (OR=4.1, P=0.000). CONCLUSIONS: We conclude that both high foot
      pressures (> or =6 kg/cm2) and neuropathy are independently associated with
      ulceration in a diverse diabetic population, with the latter having the greater
      magnitude of effect. In black and Hispanic diabetic patients especially, joint
      mobility and plantar pressures are less predictive of ulceration than in
      Caucasians.

PMID- 9773737
TI  - The STOP-NIDDM Trial: an international study on the efficacy of an alpha
      glucosidase inhibitor to prevent type 2 diabetes in a population with impaired
      glucose tolerance: rationale, design, and preliminary screening data. Study to
      Prevent Non-Insulin-Dependent Diabetes Mellitus.
AB  - OBJECTIVE: To describe the rationale and design, and to discuss the preliminary
      screening data, of the Study to Prevent NIDDM (STOP-NIDDM Trial), an
      international study on the efficacy of the alpha-glucosidase inhibitor acarbose
      in preventing or delaying the development of type 2 diabetes in a population with
      impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: A total of 1,418
      subjects diagnosed with IGT according to the World Health Organization's criteria
      and having a fasting plasma glucose concentration > or =5.6 mmol/L were
      randomized in a double-blind fashion to receive either acarbose (100 mg t.i.d.)
      or placebo for a predictive median follow-up period of 3.9 years. The primary
      outcome is the development of type 2 diabetes diagnosed using a 75-g oral glucose
      tolerance test according to the new criteria. The secondary outcomes are changes
      in blood pressure, lipid profile, insulin sensitivity, cardiovascular events, and
      morphometric profile. RESULTS: Screening was performed in a high-risk population.
      As of 1 March 1997, 4,424 subjects had been screened, and data were available for
      3,919 (88.5%) subjects. Of these subjects, 1,200 (30.6%) had glucose intolerance.
      Of the subjects with glucose intolerance, 521 (13.3%) had previously undetected
      type 2 diabetes, and 679 (17.3%) had IGT. Of the IGT population, 412 (60.7%)
      subjects were eligible for the study This population had the following
      characteristics: the mean age was 54.8 years, 52% of the subjects were female,
      53% had more than one risk factor for type 2 diabetes, >90% had a family history
      of diabetes, 78.2% had a BMI > or =27 kg/m2, 47.5% had high blood pressure, 51.2%
      had dyslipidemia, and 22.8% of the women had a history of gestational diabetes.
      CONCLUSIONS: Screening of a high-risk population yields one eligible subject per
      every 10 volunteers screened. This study should definitely answer the question of
      whether acarbose can prevent or delay the progression of IGT to type 2 diabetes
      mellitus.

PMID- 9773738
TI  - Meta-analysis of the effect of insulin lispro on severe hypoglycemia in patients
      with type 1 diabetes.
AB  - OBJECTIVE: A precise time-action profile of insulin lispro (Humalog) at mealtime
      may reduce the incidence of severe hypoglycemia. Because it is a rare
      complication, we performed a cumulative meta-analysis to compare the frequency of
      severe hypoglycemia during insulin lispro and human regular insulin therapy in
      type 1 diabetic patients. RESEARCH DESIGN AND METHODS: The analysis included
      eight large multi-center clinical trials, three with parallel and five with
      crossover designs. The studies included 2,576 type 1 diabetic patients in total,
      with 2,327 receiving insulin lispro and 2,339 receiving regular human insulin,
      representing > 1,400 patient-years of insulin therapy Severe hypoglycemia was
      defined as coma or requiring glucagon or intravenous glucose. The patients
      received either NPH or ultralente as their basal insulin and insulin lispro or
      regular human insulin before each meal. RESULTS: Seventy-two patients (3.1%) had
      a total of 102 severe hypoglycemic episodes during insulin lispro therapy
      compared with 102 patients (4.4%) with a total of 131 episodes during regular
      human insulin therapy (P=0.024). CONCLUSIONS: The results of this meta-analysis
      demonstrate that in type 1 diabetic patients, the frequency of severe
      hypoglycemia can be reduced by taking insulin lispro as compared with regular
      human insulin therapy.

PMID- 9773739
TI  - Abnormally decreased HbA1c can be assessed with erythrocyte creatine in patients
      with a shortened erythrocyte age.
AB  - OBJECTIVE: To investigate whether erythrocyte creatine can serve as a corrective
      index for HbA1c in patients with a shortened mean age of erythrocytes. RESEARCH
      DESIGN AND METHODS: HbA1c and creatine in density-fractionated erythrocytes from
      18 normal subjects were measured. HbA1c and erythrocyte creatine in the whole
      blood of 43 patients with liver cirrhosis (LC), 14 patients with hemolytic anemia
      (HA), 38 other patients with high reticulocyte counts (HRC) (>2.2%), and 59
      normal subjects were also measured. The patients in this study all had normal
      blood glucose levels. A correction formula derived from the linear regression
      equation for the correlation between HbA1c and erythrocyte creatine was used to
      correct the patients' HbA1c values. RESULTS: Among density-fractionated
      erythrocytes, the young cells exhibited low HbA1c and high creatine values. With
      progressively increasing density, HbA1c gradually increased and creatine
      gradually decreased. In the whole blood samples, the HbA1c values were
      significantly lower (P < 0.001) in LC, HA, and HRC patients than in normal
      subjects. By contrast, the erythrocyte creatine values were significantly higher
      (P < 0.001) in LC, HA, and HRC patients than in normal subjects. A linear
      correlation between HbA1c (y) and erythrocyte creatine (x) was observed (y=
      0.224x + 5.00; n=154; r=-0.70; P < 0.001). Based on the regression equation, a
      correction formula was obtained. Low HbA1c values (<4.3%) were found in 24 of the
      43 LC patients, 12 of the 14 HA patients, and 20 of the 38 HRC patients. After
      correction of the HbA1c values, 15 of the 24 LC patients, 9 of the 12 HA
      patients, and 16 of the 20 HRC patients had HbA1c values within the normal range.
      CONCLUSIONS: HbA1c decreased in inverse proportion to the increase in erythrocyte
      creatine because of a shortened mean age of erythrocytes. The abnormally
      decreased HbA1c value could be assessed with erythrocyte creatine.

PMID- 9773740
TI  - Oxidative stress at onset and in early stages of type 1 diabetes in children and
      adolescents.
AB  - OBJECTIVE: In diabetes, the persistence of hyperglycemia has been reported to
      cause increased production of oxygen free radicals through glucose autooxidation
      and nonenzymatic glycation. The aim of this study was to determine whether
      oxidative cellular damage occurs at the clinical onset of diabetes and in later
      stages of the disease in young patients. RESEARCH DESIGN AND METHODS: Indicative
      parameters of lipoperoxidation, protein oxidation, and changes in the status of
      antioxidant defense systems were evaluated in single blood samples from 54
      diabetic children, adolescents, and young adults and 60 healthy age- and sex
      matched control subjects. RESULTS: Malondialdehyde and protein carbonyl group
      levels in plasma were progressively higher in diabetic children and adolescents
      than in control subjects (P < 0.0001). The highest erythrocyte superoxide
      dismutase (SOD) activity was found in diabetic children at onset of clinical
      diabetes. In diabetic adolescents, SOD was also significantly higher (P < 0.0001)
      than in control subjects. Erythrocyte glutathione peroxidase was significantly
      lower in diabetic children and adolescents compared with control subjects (P <
      0.002). A significant decline in blood glutathione content at the recent onset of
      diabetes was found (P < 0.0001). Furthermore, our results demonstrated
      progressive glutathione depletion during diabetes evolution. The plasma alpha
      tocopherol/total lipids ratio and beta-carotene levels during diabetes
      development (P < 0.001) were low. CONCLUSIONS: This cross-sectional study in
      young diabetic patients showed that systemic oxidative stress is present upon
      early onset of type 1 diabetes and is increased by early adulthood. Decreased
      antioxidant defenses may increase the susceptibility of diabetic patients to
      oxidative injury. Appropriate support for enhancing antioxidant supply in these
      young diabetic patients may help prevent clinical complications during the course
      of the disease.

PMID- 9773741
TI  - Differential glucose tolerance in dipper and nondipper essential hypertension:
      the implications of circadian blood pressure regulation on glucose tolerance in
      hypertension.
AB  - OBJECTIVE: The goals of this study were to compare glucose tolerance in dipper
      and nondipper hypertensive patients and to explore the cause of glucose
      intolerance in essential hypertension. RESEARCH DESIGN AND METHODS: A total of 50
      patients <45 years old who had essential hypertension were recruited and studied
      by 24-h blood pressure monitoring and an oral glucose tolerance test (OGTT).
      Autonomic function was assessed with spectral analysis of heart rate variability
      RESULTS: Dipper hypertensive patients (n=25) had lower nocturnal blood pressure
      than nondipper (n=25) patients. During OGTT, postprandial glucose levels were
      higher in the nondippers at 0, 90, and 120 min (all P < 0.05). Nondippers had a
      higher fasting insulin/glucose ratio than was apparent in normal control
      subjects. Despite higher postprandial glucose levels, nondippers had lower
      postprandial insulin levels. These results suggest that nondippers were insulin
      resistant and that their pancreatic beta-cell function was impaired. For all
      patients, nocturnal reduction of blood pressure was inversely related to total
      glucose levels under the OGTT curve and was positively related to postprandial
      insulin levels. Daytime heart rate did not differ between the dippers and
      nondippers, but nocturnal heart rate was higher in the nondippers, suggesting
      that nocturnal sympathetic activities were higher among the nondippers. Spectral
      analysis of heart rate variability suggests that the nondippers had lower
      parasympathetic activities and unbalanced sympathetic/parasympathetic outflow.
      CONCLUSIONS: These findings indicate that nondipper hypertensive patients are
      more glucose intolerant than are dipper patients. The abnormalities of glucose
      metabolism in nondippers could be explained by insulin resistance and beta-cell
      dysfunction. The results of spectral analysis suggest that abnormal autonomic
      outflow may represent a possible link between hypertension and associated
      metabolic dysfunction.

PMID- 9773742
TI  - Glycemic control is related to the electrophysiologic severity of diabetic
      peripheral sensorimotor polyneuropathy.
AB  - OBJECTIVE: The aim of the present study was to examine risk factors for the
      electrophysiologic severity of diabetic peripheral sensorimotor polyneuropathy
      (DSP). RESEARCH DESIGN AND METHODS: A total of 97 patients with type 1 diabetes
      (25 patients) or type 2 diabetes (72 patients) were included in this cross
      sectional study. Nerve conduction studies (NCS) were performed on median motor
      and sensory nerves, peroneal motor nerve, and both sural nerves. The severity of
      DSP was expressed as the sum of nerve conduction velocities (SNCV) and the score
      of distal amplitudes (SAMP) of the above-mentioned nerves. General linear models
      were used to assess the relationship between overall severity of DSP as well as
      the severity of lower extremity, upper extremity, motor nerve, or sensory nerve
      involvement and various risk factors. RESULTS: GHb was significantly related to
      both SNCV and SAMP in univariate and multivariate regression analyses. This
      relationship was present in models where GHb was handled either as a continuous
      variable or as a categorical variable with highest significance level, with a GHb
      cutoff level of 9%. The difference in NCV for individual nerves in patients with
      good-to-moderate glycemic control (GHb < or =9%) and those with poor glycemic
      control (GHb > or =9%) ranged from 1.8 to 3.6 m/s. SAMP was also significantly
      lower in patients with poor control. SNCV was also significantly related in
      multivariate analysis to duration of diabetes and height, while SAMP was related
      to duration of diabetes, age, and male sex. CONCLUSIONS: The severity of DSP
      expressed by electrophysiologic criteria was significantly related to glycemic
      control in a study including patients with type 1 or type 2 diabetes. Based on
      the results of the present study, it might be predicted that better diabetic
      control would decrease the severity of DSP.

PMID- 9773743
TI  - Increased nitrotyrosine in the diabetic placenta: evidence for oxidative stress.
AB  - OBJECTIVE: To evaluate the presence of nitrotyrosine (NT) residues in placental
      villous tissue of diabetic pregnancies as an index of vascular damage linked to
      oxidative stress. RESEARCH DESIGN AND METHODS: Villous tissue was collected and
      flash frozen after delivery from 10 class C and D IDDM patients (37.9+/-3.2
      weeks) and 10 normotensive pregnant individuals (37.5+/-3.8 weeks). Serial
      sections of tissue were immunostained with specific antibodies to NT, endothelial
      nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and
      manganese superoxide dismutase (MnSOD). Sections were scored for intensity of
      immunostaining (0-3) by three observers blinded to the identity of tissue.
      RESULTS: All tissues demonstrated immunostaining for eNOS in both
      syncytiotrophoblast and stem villous vascular endothelium with no apparent
      differences between groups. Immunostaining for iNOS was seen in the villous
      stroma, but again was not different between the two groups. Significantly more
      intense NT staining was apparent in vascular endothelium and villous stroma (both
      P < 0.02) of diabetic placentas. The endothelium of large villous vessels of
      diabetic tissues also showed more intense immunostaining for MnSOD (P < 0.01).
      CONCLUSIONS: In these diabetic pregnancies, we were unable to show increased
      eNOS, unlike previous findings in preeclamptic pregnancies. The presence of NT
      may indicate vascular damage in the diabetic placenta due to peroxynitrite action
      formed from increased synthesis/interaction of nitric oxide and superoxide. The
      apparently paradoxical increase in MnSOD expression may be an adaptive response
      to increased superoxide generation.

PMID- 9773744
TI  - Hepatocyte growth factor in vitreous fluid of patients with proliferative
      diabetic retinopathy and other retinal disorders.
AB  - OBJECTIVE: To determine whether hepatocyte growth factor (HGF) is elevated in the
      vitreous fluid of patients with proliferative diabetic retinopathy (PDR).
      RESEARCH DESIGN AND METHODS: Vitreous fluid samples were obtained at the time of
      vitreoretinal surgery from 73 eyes of PDR patients and from 17 eyes of
      nondiabetic patients (control subjects) who had macular hole, rhegmatogenous
      retinal detachment, or epiretinal membrane (9, 4, and 4 eyes, respectively) but
      no associated proliferative vitreoretinopathy Stages of PDR were classified as
      active or quiescent. Concentrations of HGF and vascular endothelial growth factor
      (VEGF) in vitreous fluid were determined by enzyme-linked immunosorbent assay
      (ELISA). RESULTS: Intravitreous concentrations of HGF (median [range]) were
      significantly higher in diabetic patients with PDR (6.00 ng/ml [0.75-22.21) than
      in control patients (2.86 ng/ml [0.75-5.801). Intravitreous concentrations of
      VEGF were also higher in diabetic patients with PDR (1.62 ng/ml [0.15-7.91) than
      in control patients (0.16 ng/ml [0.160.29]). Both VEGF and HGF concentrations
      were significantly higher in patients with active retinopathy than in those with
      quiescent retinopathy However, vitreous concentrations of HGF were unrelated to
      those of VEGE CONCLUSIONS: We found that levels of HGF in vitreous fluid of PDR
      patients are significantly higher than in nondiabetic patients and that the
      levels of HGF are elevated in the active PDR stage. This suggests that HGF
      stimulates or perpetuates neovascularization in PDR.

PMID- 9773745
TI  - American Diabetes Association Annual Meeting, 1998: cardiac disease and related
      topics.

PMID- 9773746
TI  - Interferon-alpha and development of type 1 diabetes: a case without insulin
      resistance.

PMID- 9773747
TI  - Methionine synthase D919G mutation in type 2 diabetes and its relation to
      vascular events.

PMID- 9773748
TI  - Do mobile cellular phones interfere with portable insulin pumps?

PMID- 9773749
TI  - Glycemic control during exercise in type 1 diabetes: comparison of a new medical
      food bar with usual care.

PMID- 9773750
TI  - Chorea in hyperglycemia.

PMID- 9773751
TI  - Early preprandial hypoglycemia after administration of insulin lispro.

PMID- 9773752
TI  - Elevated serum tumor necrosis factor-alpha and endothelin 1 levels correlate with
      increased C-peptide concentration in android type obesity.

PMID- 9773753
TI  - Diabetes and risk of adverse events with calcium antagonists.

PMID- 9773754
TI  - Contribution of emotionally traumatic events and inheritance to the report of
      current physical health problems in 4042 Vietnam era veteran twin pairs.
AB  - OBJECTIVE: To determine the contributions of psychological trauma (exposure to
      combat during the Vietnam War), genetic factors, childhood experiences shared by
      twin siblings, and unmeasured experiences not shared by twin siblings to the
      reporting of current physical health problems a mean of 19 years after military
      service. METHODS: In 1987, a national sample of 2224 monozygotic and 1818
      dizygotic male veteran members of the Vietnam Era Twin Registry participated in a
      survey of health. Genetic modeling was performed on cross-sectional physical
      health and combat exposure data derived from Registry twins. RESULTS: Combat
      experiences explained a small proportion (0.7-8.4%) of the variance in the report
      of hypertension, respiratory conditions, persistent skin conditions,
      gastrointestinal disorders, joint disorders, and hearing problems. Childhood
      experiences shared by siblings are not clearly related to any health problem
      studied. By contrast, genetic factors explain 31 to 54% and noncombat experiences
      not shared by siblings explain 45 to 66% of the variance in current physical
      health status. CONCLUSIONS: Greater than 90% of the variance in reported current
      physical health problems in Vietnam era veterans is attributable to inherited
      factors and unmeasured environmental experiences not shared by twin siblings. The
      traumatic experience of combat makes only a small contribution to the report of
      current physical health problems. These results do not preclude the possibility
      that combat influenced the prevalence of illness shortly after military service
      or that combat may influence the development of illness in the future.

PMID- 9773755
TI  - Into the MIRE: stress, genetics, and disease.

PMID- 9773756
TI  - Course of distress experienced by persons at risk for an autosomal dominant
      inheritable disorder participating in a predictive testing program: an
      explorative study. Rotterdam/Leiden Genetics Workgroup.
AB  - OBJECTIVE: To compare the effects of predictive DNA testing on participants at
      risk for either Huntington disease (HD), or familial adenomatous polyposis (FAP),
      or hereditary breast and ovarian cancer (HBOC). METHOD: Psychological distress
      was measured with the Impact of Event Scale before testing and at 1 week and 6
      months after the test result, in individuals at 50% risk for either HD (N = 25),
      FAP (N = 23), or HBOC (N = 10). RESULTS: A marginally significant trend was found
      indicating that carriers of the disease genes tended to show unchanged levels of
      distress during the study period whereas noncarriers showed the expected
      decrease. Men reported significantly less distress than women, and 1 week after
      the test result male noncarriers showed a sharp significant increase in the
      reported distress followed by a steady decline up to 6 months later. CONCLUSIONS:
      The course of distress over time reported by carriers and noncarriers of the
      three disease genes was similar, which leads one to conclude that the previous
      experience with predictive testing for Huntington Disease may be a useful
      paradigm. However, those formerly at risk for HD reported more distress than
      those at risk for FAP and HBOC. From our clinical experience we learned that
      individuals at risk for FAP and HBOC are more inclined to ward off the emotions
      involved. Additional qualitative studies should be undertaken to investigate
      this.

PMID- 9773757
TI  - Clinical correlation of neuropsychological tests with 1H magnetic resonance
      spectroscopy in hepatic encephalopathy.
AB  - OBJECTIVE: The purpose of this project was to correlate neuropsychological test
      results with in vivo measures of regional cerebral biochemistry determined by 1H
      MRS in patients with subclinical and mild hepatic encephalopathy. METHODS:
      Baseline 1H MRS scans and neuropsychological testing of patients occurred at
      entry into the study. The primary localized volume chosen for the 1H MRS study
      was the posteromedial parietal cortex, which consisted predominantly of white
      matter. Some of these patients were scanned again if they received a liver
      transplantation. In a subset of patients, the effect on cerebral biochemistry and
      neuropsychological test performance due to a dietary intervention of reduced
      protein intake was monitored. These patients underwent a baseline examination and
      a repeat examination after 2 weeks of dietary intervention. Measures were made of
      the correlation between the dietary intervention and 1H MRS determined
      biochemistry and the results of neuropsychological tests. Results in both patient
      groups (dietary intervention and no dietary intervention) were compared with
      healthy control subjects. RESULTS: Subclinical and low grade HE patients showed a
      significant reduction in mI/Cr and Cho/Cr ratio when compared with healthy
      control subjects. These patients also showed impairment in frontal lobe mediated
      cognitive tasks and in motor ability that were not appreciated in a bedside
      examination. The patients did not return to normal cerebral metabolic states
      within 30 to 60 days of liver transplantation. In fact, reductions remained in
      mI/Cr. Cho/Cr values increased after transplantation compared with healthy
      control subjects. CONCLUSIONS: 1H MRS studies showed changes in regional cerebral
      biochemistry associated with all grades of HE. There was a reduction in mI/Cr and
      a reduction in Cho/Cr in patients with low grade and subclinical forms of HE
      compared with normal subjects. The reduction in mI correlated well with
      abnormalities observed in neuropsychological tests. Liver transplantation was not
      associated with significant improvement in these variables.

PMID- 9773758
TI  - Palpitations and cardiac awareness after heart transplantation.
AB  - OBJECTIVE: The aim of this study was to examine the awareness of resting
      heartbeat in heart transplantation recipients, compare it with that found in
      other medical populations, and determine whether clinical characteristics are
      associated with accurate heartbeat awareness. METHODS: Eligible patients
      underwent a research battery consisting of a heartbeat detection task and self
      report questionnaires assessing cardiac symptoms, psychosocial variables, and
      cognitive function. The accurate awareness of resting heartbeat was determined by
      presenting the patients with auditory stimuli at each of six different delays
      following the R wave on the ECG. Patients then selected the tones that they
      thought coincided with the sensation they had of their heart beating. The
      patients' physicians rated their cardiac morbidity. The results were contrasted
      with comparable data obtained in previous work with other ambulatory medical
      populations. RESULTS: Forty-one consecutive heart transplantation recipients who
      survived for at least 3 months after surgery were eligible. Thirty-four (82.9%)
      of them were studied and complete data were obtained on 26 (63.4%). Nine patients
      (34.6%) were reliably able to detect their resting heartbeat. When compared with
      the 17 patients who were not accurately aware of their heartbeat, the two groups
      did not differ significantly in cardiac morbidity, cognitive brain dysfunction,
      generalized psychiatric distress, depression, somatization, or hypochondriacal
      attitudes. A significantly higher proportion of heart transplantation recipients
      were accurately aware of their heartbeat than was found in a sample of general
      medical outpatients and in asymptomatic, nonpatient volunteers. CONCLUSIONS: One
      third of heart transplant recipients are accurately aware of resting heartbeat,
      despite the absence of cardiac innervation.

PMID- 9773759
TI  - Self-report evaluation of health behavior, stress vulnerability, and medical
      outcome of heart transplant recipients.
AB  - OBJECTIVE: The purpose of this study was to explore the value of patient self
      report assessment in heart transplant candidacy evaluation, utilizing the Millon
      Behavioral Health Inventory (MBHI). Patient's MBHI measures were related to
      important pretransplant patient characteristics and posttransplant measures of
      health behavior, medical morbidity, and mortality. METHOD: Ninety heart patients
      with end-stage cardiac disease completed the MBHI during pretransplant candidacy
      evaluations, and also were interviewed concerning their coping effectiveness,
      support resources, and compliance history. Postransplant follow-up of 61 living
      and 29 deceased patients included measures of survival time, postsurgical medical
      care, rejection and infection episodes, and nurse ratings of medication
      compliance and problematic interpersonal health behaviors. RESULTS: The MBHI
      coping scales were found to significantly discriminate good and poor
      pretransplant compliance, and interview judgments of good and poor coping and
      support resources, with modest accuracy. The MBHI also was superior to these
      interview judgments in predicting posttransplant survival time and medical care
      used. Certain scales were also positively associated with physical parameters of
      pretransplant and posttransplant status. CONCLUSIONS: Patient self-report with
      the MBHI can contribute to identification of patients at risk for a problematic
      outcome with transplant, by providing information pertinent to clinical decision
      making and outcome management analysis with this special population of cardiac
      patients.

PMID- 9773761
TI  - Is educational attainment associated with shared determinants of health in the
      elderly? Findings from the MacArthur Studies of Successful Aging.
AB  - OBJECTIVE: To investigate the association of educational attainment with an array
      of risk factors for poor health among high-functioning older men and women.
      METHODS: Cross-sectional analyses of psychosocial, behavioral, and biological
      factors and educational attainment were conducted using data from a population
      based cohort study of older men and women. Participants consisted of 70- to 79
      year-old residents of communities of East Boston, MA; New Haven, CT; and Durham
      County, NC (N = 1192) participating in the Established Populations for
      Epidemiologic Studies of the Elderly programs, a three-site longitudinal study of
      community-dwelling men and women. Participants were selected on the basis of high
      physical and cognitive function, representing approximately the top third of
      their peers in terms of functional ability in 1988. In-home interviews were
      conducted. Associations among education and behavioral (e.g., cigarette smoking
      and physical activity), biological (e.g., pulmonary function, serum cholesterol),
      psychological (e.g., self-efficacy, anxiety), and social (e.g., networks and
      support) factors were examined. RESULTS: Low levels of education were associated
      with poorer psychological function (less mastery, efficacy, happiness), less
      optimal health behaviors (increased tobacco consumption and decreased levels of
      physical activity), poorer biological conditions (decreased pulmonary function,
      increased body mass index and waist-to-hip ratio), and larger social networks
      (increased number of contacts, decreased negative support). Several factors
      (alcohol consumption, high-density lipoprotein cholesterol) were nonlinearly
      related to educational attainment. CONCLUSIONS: Educational attainment is
      associated with a broad array of psychosocial and biological conditions among the
      elderly. That an education gradient functions over an array of factors that
      structure daily life, even in later life in a healthy population, may suggest how
      socioeconomic status influences health.

PMID- 9773760
TI  - Diagnostic groups and depressed mood as predictors of 22-month mortality in
      medical inpatients.
AB  - OBJECTIVE: While depression has been found to predict mortality in acute
      myocardial infarction, results from many other groups of medical patients are
      inconclusive. It is, therefore, unclear whether depression also predicts
      mortality in the typical mixed patient populations treated on medical hospital
      wards and whether an increased risk can be identified by means of patients' self
      ratings of depression. METHOD: The Hospital Anxiety and Depression scale was used
      as a routine screening tool in consecutive admissions to the general medical
      wards of a university hospital. The official survival data were obtained 22
      months later. For all 454 patients who completed the screening questionnaire,
      complete survival data were available. RESULTS: High depression scores
      significantly predicted mortality in univariate comparisons (odds ratio 3.2; 95%
      CI 1.9-5.5) and in multivariate Cox regression analyses controlling for
      demographic and medical baseline variables (multivariate odds ratio 1.9; 95% CI
      1.2-3.1; p < .01). Other significant predictors in the multivariate model were
      having a principal diagnosis of hematological disease or cancer, and older age.
      Disability, as assessed by nurses' ratings, and gender were not related to
      mortality. Subgroup analyses showed that the effect of depression scores was
      greatest in cardiopulmonary patients, but there was also a uniform trend toward
      higher mortality in depressed patients with other diagnoses. CONCLUSION:
      Depressed mood is an independent risk factor for all-cause mortality in medical
      inpatients. Identifying patients at risk does not require formal psychiatric
      diagnoses, but can be achieved by means of a short, routinely administered self
      rating questionnaire.

PMID- 9773762
TI  - Hostility is associated with increased platelet activation in coronary heart
      disease.
AB  - OBJECTIVE: To determine whether Potential for Hostility is related to platelet
      activation (PA) among patients with coronary heart disease (CHD) and healthy
      controls. Increased PA has been associated with adverse secondary events after
      myocardial infarction or coronary angioplasty. METHODS: We tested 32 CHD patients
      and 23 healthy men and women, aged 45 to 73 years, for PA by using whole blood
      flow cytometry. PA was measured in blood exiting a bleeding time wound (wound
      induced platelet activation) and also in venous blood stimulated in vitro with
      collagen. Monoclonal antibodies were used to test for fibrinogen receptor
      activation and fibrinogen receptor binding. All subjects refrained from taking
      aspirin for at least 14 days before testing; CHD patients stopped nitrates and
      calcium channel blockers for 24 hours, while continuing to take lipid-lowering
      medications. Potential for Hostility was assessed, using the Type A Structured
      Interview. RESULTS: Among the CHD patients only, all four of the wound-induced
      fibrinogen receptor activation indicators (activation and binding) were related
      to hostility; the relationships were significant for receptor activation at 2
      minutes, and for receptor binding at 1 minute (r values = .46, p values = .02).
      Subjects on lipid-lowering medications had lower PA for most measures. Healthy
      subjects had higher wound-induced fibrinogen receptor activation at 2 minutes and
      fibrinogen receptor activation in vitro than the CHD patients (p = .04), but
      after statistical adjustment for lipid-lowering medications, there were no
      significant differences between the patients and controls. CONCLUSIONS: PA was
      related to hostility among CHD patients, consistent with previous studies
      indicating a relationship between PA and psychological factors among CHD
      patients. However, PA was not increased in nonsmoking, nondepressed CHD patients
      relative to controls.

PMID- 9773763
TI  - Psychosocial factors influencing the short-term outcome of antithyroid drug
      therapy in Graves' disease.
AB  - OBJECTIVE: Although psychological stress and smoking have been proposed as
      factors contributing to Graves' disease, their independent roles in the course of
      this disease have not been determined. We assessed the association between the
      course of Graves' disease and psychosocial factors by using multivariate
      analysis. METHODS: We investigated the association between the short-term outcome
      of Graves' disease (assessed 12 months after the beginning of antithyroid drug
      therapy) and stressful life events, daily hassles, smoking, drinking habits,
      coping skills, and social support (before and 6 months after beginning therapy)
      in 230 patients (182 women and 48 men) with newly diagnosed Graves' disease,
      using a logistic regression model. RESULTS: After adjustment for smoking, coping
      skills, and thyroid function, daily hassles scores in women at 6 months after
      beginning therapy were significantly associated with a hyperthyroid state 12
      months after beginning therapy. The relative risk was 3.9 for women with higher
      daily hassles scores compared with women with lower daily hassles scores (95%
      confidence interval, 1.1 to 13.2; p < .05). Smoking was not significantly
      associated with a hyperthyroid state 12 months after beginning therapy in either
      women or men. CONCLUSIONS: Chronic psychological stress is associated with the
      course of Graves' disease in women.

PMID- 9773764
TI  - Chronic stress and illness in children: the role of allostatic load.
AB  - OBJECTIVE: Recent studies of stress have highlighted the contributions of chronic
      psychological and environmental stressors to health and well-being. Children may
      be especially vulnerable to the negative effects of chronic stressors.
      Allostasis, the body's ability to adapt and adjust to environmental demands, has
      been proposed as an explanatory mechanism for the stress-health link, yet
      empirical evidence is minimal. This study tested the proposition that allostasis
      may be an underlying physiological mechanism linking chronic stress to poor
      health outcomes in school-aged children. Specifically, we examined whether
      allostasis would mediate or moderate the link between chronic stress and health.
      METHOD: To test the hypothesis that allostasis contributes to the relation
      between chronic stress and poor health, we examined household density as a
      chronic environmental stressor, cardiovascular reactivity (CVR) as a marker of
      allostatic load, and number of school absences due to illness as the health
      outcome in a sample of 81 boys. RESULTS: Structural equation modeling indicated
      that the mediating model fit the data well, accounting for 17% of the variance in
      days ill. CONCLUSIONS: Results provide the first evidence that CVR may mediate
      the relation between household density and medical illness in children. More
      generally, these findings support the role of allostasis as an underlying
      mechanism in the link between chronic stress and health.

PMID- 9773765
TI  - Cardiorespiratory symptoms in response to physiological arousal.
AB  - OBJECTIVE: To develop a laboratory paradigm for assessing the tendency to amplify
      somatic symptoms and report bodily distress. METHOD: Reports of four different
      cardiopulmonary symptoms were obtained during standardized, treadmill exercise,
      while the physiological parameters which induce these symptoms were
      simultaneously measured. Two indices were developed to compare symptom reporting
      across patients: symptom severity after reaching 80% of predicted, maximal
      exercise capacity; and the magnitude of physiological arousal necessary to induce
      an initial sensation of discomfort. RESULTS: Fifty-one medical outpatients with a
      chief complaint of palpitations were studied. Symptom distress at 80% of maximal
      exercise capacity was significantly associated with state anxiety and daily life
      stress. The complaint of "heart racing" first occurred at a significantly lower
      heart rate for patients who were older, more anxious, and reported more daily
      life stress. Measures of hypochondriasis, somatization, bodily amplification, and
      bodily absorption were not significantly associated with either symptom measure.
      CONCLUSIONS: Standardized exercise testing may provide a suitable paradigm with
      which to study the tendency to amplify symptoms and to somatize. The distress
      reported by different subjects at 80% of maximal exercise capacity may be
      considered an index of the discomfort engendered by a standardized stimulus,
      whereas the point of onset of discomfort may be a measure of the patient's
      threshold for becoming symptomatic. These findings are not conclusive, but do
      suggest that patients who are more anxious and under more stress tend to report
      more intense cardiopulmonary symptoms at comparable levels of physiological
      arousal, and to have a lower threshold for experiencing discomfort.

PMID- 9773766
TI  - Heart rate variability in insomniacs and matched normal sleepers.
AB  - OBJECTIVE: It was hypothesized that psychophysiological insomniacs, who have been
      shown to have elevated heart rate, body temperature, and whole body metabolic
      rate, would also have increased low frequency and decreased high frequency power
      in the spectral analysis of their heart period data. METHOD: Groups of 12
      objectively defined insomniacs and age-, sex-, and weight-matched controls with
      normal sleep were evaluated on sleep and EKG measures over a 36-hour sleep
      laboratory stay. RESULTS: Heart period was decreased (ie, heart rate was
      increased) and its SD was decreased in all stages of sleep in the insomniacs
      compared with the controls. Spectral analysis revealed significantly increased
      low frequency power and decreased high frequency power in insomniacs compared
      with controls across all stages of sleep. CONCLUSIONS: Because increased low
      frequency spectral power is an indicator of increased sympathetic nervous system
      activity, these data imply that chronic insomniacs could be at increased risk for
      the development of disorders, such as coronary artery disease, that are related
      to increased sympathetic nervous system activity.

PMID- 9773767
TI  - Association between somatic symptoms and 24-hour ambulatory blood pressure
      levels.
AB  - OBJECTIVE: To clarify whether somatic complaints in healthy normotensive men are
      associated with differential 24-hour blood pressure and heart rate measures.
      METHOD: Twenty-four-hour ambulatory systolic and diastolic blood pressure was
      monitored in 114 healthy normotensive men, aged 28 to 63 years, engaged in
      similar physical work. Means were calculated for each hour, for the whole 24-hour
      period, and for daytime, nighttime, and work time. Subjects were interviewed
      about somatic complaints, demographic data, and health habits, and body mass
      index was measured. RESULTS: After controlling for possible confounders, a
      positive association was found between the somatic complaint score and 24-hour,
      diurnal, and work-time systolic blood pressure (p = .014, p = .007, and p = .008,
      respectively). The association with casual systolic blood pressure was of
      borderline significance (p = .089). There was a positive trend, which did not
      reach statistical significance, in the relationship between somatic complaint
      score and all measures of diastolic blood pressure. Diurnal, 24-hour, and work
      time heart rates were highest in the subjects with the highest somatic scores (p
      < .01 for all trends). CONCLUSIONS: In healthy normotensive men, somatic
      complaints are associated with an increased cardiovascular load. The effects of
      this increase on long-term cardiovascular morbidity and mortality are uncertain
      and warrant additional study.

PMID- 9773768
TI  - John Henryism, gender, and arterial blood pressure in an African American
      community.
AB  - OBJECTIVE: To examine the interaction between gender and John Henryism in
      relationship to arterial blood pressure in an African American community in the
      Southern United States. It was hypothesized that, within this specific social and
      cultural context, John Henryism would be associated with blood pressure
      differently for men and women. METHODS: A cross-sectional survey of 600 persons,
      aged 25 to 65, was conducted in the African American community of a small
      Southern city. John Henryism was assessed using the 12-item John Henryism Scale
      for Active Coping. Blood pressure was assessed by conventional methods. RESULTS:
      The interaction effect between gender and John Henryism was assessed as a cross
      product term in ordinary least squares regression analysis using arterial blood
      pressure as the dependent variable, and with logistic regression using
      hypertension as the dependent variable. This interaction effect was significant
      (p < .05) in relation to systolic blood pressure and hypertension, with the
      effect evident (p < .07) in relation to diastolic blood pressure. For men, as
      John Henryism increases, blood pressure and the risk of hypertension increases.
      For women, as John Henryism increases, blood pressure and the risk of
      hypertension decreases. CONCLUSIONS: The association of the behavioral
      disposition of John Henryism with blood pressure is dependent on the gender of
      the individual. Men and women face differing cultural expectations and social
      structural constraints in this community. The sociocultural context modifies the
      meaning of the behavioral disposition, and hence its effects.

PMID- 9773769
TI  - Influence of a mindfulness meditation-based stress reduction intervention on
      rates of skin clearing in patients with moderate to severe psoriasis undergoing
      phototherapy (UVB) and photochemotherapy (PUVA).
AB  - OBJECTIVE: This study tests the hypothesis that stress reduction methods based on
      mindfulness meditation can positively influence the rate at which psoriasis
      clears in patients undergoing phototherapy or photochemotherapy treatment.
      METHODS: Thirty-seven patients with psoriasis about to undergo ultraviolet
      phototherapy (UVB) or photochemotherapy (PUVA) were randomly assigned to one of
      two conditions: a mindfulness meditation-based stress reduction intervention
      guided by audiotaped instructions during light treatments, or a control condition
      consisting of the light treatments alone with no taped instructions. Psoriasis
      status was assessed in three ways: direct inspection by unblinded clinic nurses;
      direct inspection by physicians blinded to the patient's study condition (tape or
      no-tape); and blinded physician evaluation of photographs of psoriasis lesions.
      Four sequential indicators of skin status were monitored during the study: a
      First Response Point, a Turning Point, a Halfway Point, and a Clearing Point.
      RESULTS: Cox-proportional hazards regression analysis showed that subjects in the
      tape groups reached the Halfway Point (p = .013) and the Clearing Point (p =
      .033) significantly more rapidly than those in the no-tape condition, for both
      UVB and PUVA treatments. CONCLUSIONS: A brief mindfulness meditation-based stress
      reduction intervention delivered by audiotape during ultraviolet light therapy
      can increase the rate of resolution of psoriatic lesions in patients with
      psoriasis.

PMID- 9773770
TI  - Are hostility and anxiety associated with carotid atherosclerosis in healthy
      postmenopausal women?
AB  - OBJECTIVE: In this article, we evaluated the prospective association between
      measures of trait anger, hostility, and anxiety and indices of carotid
      atherosclerosis in 200 healthy middle-aged postmenopausal women. METHODS:
      Starting in 1983, 541 premenopausal women were evaluated for their levels of
      standard cardiovascular risk factors and psychosocial attributes, including their
      scores on Spielberger Trait Anger, Anxiety, and Anger-in, and Public Self
      Consciousness. Starting in 1991, the Cook-Medley Hostile Attitudes Scale was also
      administered. Starting in 1993, 200 women who had been menopausal for at least 5
      years were scanned for carotid atherosclerosis using B-mode ultrasound. The scans
      were scored for average intima-media thickness (IMT) and plaque index. RESULTS:
      Women who had high Trait Anger, Anger-In, and Public Self-Consciousness scores
      had high IMT scores on average 10 years later. Women who had high Cook-Medley
      scores also had high IMT scores on average 1.5 years later. Multivariate analyses
      adjusting for the standard cardiovascular risk factors that most highly predicted
      IMT scores indicated that holding anger in, being self aware, and having hostile
      attitudes were significant predictors of IMT. Women with higher plaque scores
      also tended to report holding in their anger. CONCLUSIONS: Anger suppression and
      hostile attitudes do predict women's carotid IMT in midlife. Ultrasound measures
      of carotid atherosclerosis can be used to advance our understanding of the early
      development of atherosclerosis in women.

PMID- 9773772
TI  - CD4 and CD8 counts are associated with interactions of gender and psychosocial
      stress.
AB  - OBJECTIVE: This study examined relationships of gender, psychosocial
      stress/distress (caregiving, hassles, depressed mood), and the relative
      percentage and absolute cell counts of CD4 and CD8 cells in two samples of older
      adults (mean age = 69.4)--spouse caregivers of persons with Alzheimer's disease
      (N = 78) and age- and gender-matched spouses of nondemented controls (N = 72).
      METHODS: Counts and percentages of CD4 and CD8 cells and psychosocial variables
      were assessed twice (Time 1, Time 2) over a 15- to 18-month period. Several
      covariates were examined in the analyses, including body mass index (BMI),
      medication use, alcohol use, exercise, and illness history. RESULTS: Caregiver
      men had fewer CD4 cell counts at Times 1 and 2 than did control men (p < .05). At
      Times 1 and 2, both CD8 cell counts and percentages were positively associated
      with hassles in men (p < .05), but not in women. Although interactions of hassles
      and gender were present for CD8 percentages at both times, interactions and main
      effects were not present for CD4 percentages at either time. When the ratio of
      CD4 to CD8 levels was analyzed, hassles by gender interactions were present at
      both Times 1 and 2-hassles were negatively associated with the CD4/CD8 ratio in
      men (p < .05), but unrelated in women. From Time 1 to Time 2, change analyses
      showed that increases in hassles scores were associated with decreases in CD4
      counts (p < .05), whereas increases in Hamilton Depression Scores were related to
      increases in both CD8 counts and percentages (p < .05). CONCLUSION: Caregiver
      status, hassles, and depressed mood had cross-sectional and/or longitudinal
      associations with CD4 and CD8 counts, but such relationships occurred primarily
      in men. Moreover, absolute cell counts were more related to psychosocial factors
      than were percentages.

PMID- 9773771
TI  - Blood pressure reactivity and marital distress in employed women.
AB  - OBJECTIVE: The impact of marital distress on cardiovascular responses to an
      "ecologically valid" laboratory stressor (a marital conflict recall task) was
      examined in maritally distressed and non-distressed women. It was hypothesized
      that the presence of high levels of marital distress would be associated with
      elevated blood pressure and heart rate responses to a marital conflict task.
      METHOD: Fifty married, employed women, aged 25-45, were recruited into high and
      low marital distress groups, based on total scores on the Dyadic Adjustment
      Scale. Subjects participated in three laboratory stress tasks: a marital conflict
      recall task, a work conflict recall task, and a serial subtraction task. RESULTS:
      During the marital conflict recall task, women characterized as high in marital
      distress exhibited higher systolic blood pressure (M = 21.4 +/- 9.1 vs. 17.3 +/-
      7.7) (p < .05) and heart rate (M = 13.6 +/- 9.5 vs. 10.9 +/- 6.5) (p < .01)
      responses, compared with low-distress women. However, the association between
      marital distress and cardiovascular response was statistically significant only
      after aggregate responses to the control stressors were used as covariates.
      CONCLUSION: These data indicate that the stress associated with recalling a
      marital conflict was manifest in elevated blood pressure and heart rate,
      particularly among women characterized as experiencing high levels of distress in
      their marriage. Future research is needed to determine whether the blood pressure
      differences between women who are satisfied with their marriage, versus those
      that are chronically distressed are clinically meaningful. In addition,
      examination of the "ecological validity" of laboratory stressors suggests that a
      useful methodology may be to assess task responses, while controlling for
      nonspecific individual differences in cardiovascular reactivity.

PMID- 9773773
TI  - Positive perceptions of parental caring are associated with reduced psychiatric
      and somatic symptoms.
AB  - OBJECTIVE: In a previous 35-year follow-up investigation to the Harvard Mastery
      of Stress Study, positive ratings of parental caring obtained in healthy male
      college students were found to be predictive of substantially reduced disease
      incidence (including cardiovascular disease, ulcers, and alcoholism) in mid-life.
      The present cross-sectional study examined the relationship between perceptions
      of parental caring, current psychiatric and somatic symptoms, and defensiveness,
      in a University of Arizona sample of females and males. METHOD: The Harvard
      Parental Caring Scale (HPCS), the SCL90R, and the Marlowe-Crowne (MC) scale (a
      measure of defensiveness) were administered to 398 students at the University of
      Arizona. RESULTS: Cronbach alphas were .83 for HPCS ratings of mothers and .88
      for fathers. High HPCS ratings were associated with reduced symptoms reports in
      both females and males (p < .00002). Ratings of HPCS showed a small correlation
      with defensiveness (r = .141). The relationship between HPCS and symptoms was
      strongest in the least defensive subjects. CONCLUSIONS: Positive perceptions of
      love and caring from parents, typically the most important source of social
      support for children, are associated with reduced psychiatric and somatic
      symptoms. Defensiveness may play a protective role psychologically (but not
      necessarily physiologically) in reducing the conscious awareness of symptoms
      accompanying low perceptions of parental love and caring.

PMID- 9773774
TI  - Trichobezoars in trichotillomania: case report and literature overview.
AB  - OBJECTIVE: Although trichobezoars are well described in the surgical literature,
      there is relatively little in the psychiatric literature on them. This study aims
      to focus the attention of readers on trichobezoars by means of a case report and
      an overview of the literature. METHOD: We present a case of a patient with
      trichotillomania and a trichobezoar, including psychiatric management. We also
      briefly review the relevant literature. RESULTS: Hair-pulling significantly
      improved in response to treatment with the selective serotonin reuptake inhibitor
      fluoxetine and supportive psychotherapy. CONCLUSIONS: The medical and psychiatric
      sequelae of trichotillomania should not be underestimated. Pharmacotherapy may be
      play a useful role in some patients with this disorder.

PMID- 9773775
TI  - Exploring the relationship of erotic life to bulimia nervosa.

PMID- 9773776
TI  - Megalin is an endocytic receptor for insulin.
AB  - Renal clearance is a major pathway for regulating the levels of insulin and other
      low molecular weight polypeptide hormones in the systemic circulation. Previous
      studies have shown that the reabsorption of insulin from the glomerular filtrate
      occurs by binding to as yet unidentified sites on the luminal surface of proximal
      tubule cells followed by endocytosis and degradation in lysosomes. In this study,
      an insulin binding site was identified in renal microvillar membranes by chemical
      cross-linking procedures. By immunoprecipitation it was demonstrated that this
      binding site is megalin, the large multiligand binding endocytic receptor that is
      abundantly expressed in clathrin-coated pits on the apical surface of proximal
      tubule cells. Moreover, using cytochemical procedures, it was also shown that
      megalin is able to internalize insulin into endocytic vesicles. In ligand
      blotting assays, megalin also bound several other low molecular weight
      polypeptides, including beta2-microglobulin, epidermal growth factor, prolactin,
      lysozyme, and cytochrome c. These data suggest that megalin may play a
      significant role as a renal reabsorption receptor for the uptake of insulin and
      other low molecular weight polypeptides from the glomerular filtrate.

PMID- 9773778
TI  - Immunolocalization of natriuretic peptide receptor B in the rat kidney.
AB  - The natriuretic peptide receptor (NPR) family consists of three receptor
      subtypes: two transmembrane forms that contain a guanylyl cyclase intracellular
      domain (NPR-A and NPR-B), and one truncated form (NPR-C). Because of the lack of
      specific agonists and antagonists for each receptor subtype and to the difficulty
      to detect the presence of small quantities of NPR-B by ligand binding studies,
      polyclonal antibodies against a peptide whose sequence was chosen from a region
      of the extracellular domain of rat NPR-B that is not homologous to sequences in
      NPR-A and NPR-C were developed. Western blotting with affinity-purified anti-NPR
      B (413-426)-Tyr revealed a polypeptide of approximately 120 kD on COS-1 cell
      membranes transfected with rat NPR-B cDNA. The antibody recognized a second
      polypeptide, approximately 5 to 10 kD smaller, which probably represents the
      unglycosylated receptor. Anti-NPR-B (413-426)-Tyr did not show crossreactivity to
      any other NPR. Western blotting analysis with anti-NPR-B (413-426)-Tyr also
      identified a protein of appropriate size in renal vascular membranes. These
      results were supported by immunohistochemistry findings that demonstrated
      staining for NPR-B on papillary and medullary capillaries, glomeruli, and renal
      arteries. This study concludes that NPR-B is present in the rat kidney, although
      it was only detected in vascular structures.

PMID- 9773777
TI  - Characterization of a kidney proximal tubule cell line, LLC-PK1, expressing
      endocytotic active megalin.
AB  - Reabsorption and cellular handling of glomerular filtered vitamins, peptides, and
      hormones in the proximal tubule are essential, but thus far, poorly elucidated
      processes. The multiligand receptor megalin, initially described as a Heymann
      nephritis antigen and later identified as a member of the LDL receptor gene
      family, mediates reabsorption of several molecules, such as transcobalamin
      vitamin B12 and albumin, in the proximal tubule. Consequently, a differentiated
      cell line of proximal tubular origin expressing megalin is an important requisite
      for examination of the above-mentioned processes. This study shows, using
      electron microscopy, that the cell line LLC-PK1, originating from the proximal
      tubule, maintained differentiated morphology and had a well developed endocytotic
      apparatus. Furthermore, by immunoblotting and immunohisto- and cytochemistry,
      megalin was identified in the endocytotic compartments of these cells. Megalin
      was situated mainly in the endosomes and in the dense apical tubules, but it was
      also identified in coated pits and in the brush border. The ability of megalin to
      mediate internalization and degradation of labeled receptor-associated protein
      (RAP) in a RAP-inhibitable manner was demonstrated. By autoradiography, the
      endocytosed, iodinated RAP was located in endosomes and lysosomes in the apical
      part of the cells. Moreover, the LLC-PK1 cells assembled in a monolayer with a
      hindrance toward diffusion of labeled mannitol, inulin, and dextran at a
      satisfactory level for the study of proximal tubule handling of smaller proteins.
      This study reveals a proximal tubule cell line expressing megalin in a functional
      manner well suited for binding, uptake, and transcellular transport studies.

PMID- 9773779
TI  - The actin cytoskeleton and integrin expression in the recovery of cell adhesion
      after oxidant stress to a proximal tubule cell line (JTC-12).
AB  - This study examines the role of the actin cytoskeleton and integrin expression in
      the recovery of cell adhesion in the proximal tubule cell line JTC-12 after
      peroxide injury. The cells were exposed to 10, 20, or 50 mM hydrogen peroxide for
      10 min and then allowed to recover. Viability measurements by trypan blue
      exclusion confirmed that the injury was largely nonlethal with 85% viability at 1
      h even at 50 mM peroxide. ATP levels fell immediately after the peroxide
      incubation in all groups to approximately 10% of normal, but already showed some
      recovery by 1 h and full recovery in the 10 and 20 mM groups by 24 h. Cell
      adhesion to extracellular matrix immediately after injury was depressed at 20 and
      50 mM peroxide, but by 12 h was abnormal only at 50 mM peroxide and at 24 h was
      essentially normal at all peroxide concentrations. Immediately after exposure to
      10 mM peroxide, there were subtle abnormalities in the actin cytoskeleton
      (thickening of fibrils) as assessed by phalloidin staining, with more pronounced
      effects at 20 and 50 mM. At 1 h, many cells showed collapse of the actin
      cytoskeleton to the periphery. There was some recovery at 4 h; by 12 h, the actin
      cytoskeleton showed further recovery, although was still abnormal (coarsened
      microfilaments), especially at 20 and 50 mM peroxide. By 24 h, the actin
      cytoskeleton showed only subtle coarsening. Integrin surface expression was
      assessed by flow cytometry. The alpha6 subunit on cells exposed to 20 mM peroxide
      was unchanged at 1 h and 4 h, but by 12 h had increased to 118.5+/-4.5% and by 24
      h to 146+/-13.4% of control levels. The expression of the beta1 and alphaVbeta3
      integrins remained unchanged. Thus, despite coarsening of the actin cytoskeleton
      and depressed ATP levels, cell adhesion recovered from oxidant stress. Abnormal
      cell adhesion after injury was not a consequence of a decrease in integrin
      expression, and recovery of cell adhesion was not a consequence of the modest and
      selective increase in integrin expression.

PMID- 9773781
TI  - Improved survival and amelioration of nephrotoxic nephritis in intercellular
      adhesion molecule-1 knockout mice.
AB  - Intercellular adhesion molecule-1 (ICAM-1) expression is upregulated in
      nephrotoxic nephritis, a model of human rapidly progressive glomerulonephritis.
      To evaluate the pathogenetic relevance of ICAM-1 in this model, nephrotoxic
      nephritis was induced in ICAM-1 knockout mice and genetic controls. Mice were
      preimmunized with rabbit IgG in complete Freund's adjuvant. Seven days later they
      received rabbit anti-mouse glomerular basement membrane IgG. The early humoral
      immune responses (levels of circulating mouse anti-rabbit IgG, glomerular
      deposition of rabbit and mouse IgG and mouse C3c) were not altered in ICAM-1
      knockout mice. During 28 d of follow-up, 3 of 19 control nephritic mice and 0 of
      16 ICAM-1 knockout mice died. Proteinuria was high in nephritic control mice
      (means 10 to 12 mg/24 h at all time points investigated) and significantly
      reduced in nephritic ICAM-1 knockout mice (means <4.4 mg). Mean serum creatinine
      rose from 29 micromol/L at day -7 to 48 micromol/L (day 28) in nephritic control
      mice. This increase in serum creatinine was significantly lower in ICAM-1
      knockout mice: 27 (day -7) and 36 micromol/L (day 28). Histologic analysis at day
      28 revealed that ICAM-1 deficiency in nephrotoxic nephritis mice led to
      significantly reduced glomerular crescent formation (2+/-3% in ICAM-1 knockout
      mice versus 13+/-8% in nephritic controls) and tubulointerstitial injury (score
      0.4+/-0.4 versus 2.0+/-1.1). By immunohistochemistry, ICAM-1 deficiency in
      nephritic mice led to significantly reduced (peri-)glomerular and/or interstitial
      macrophage influx, alpha-smooth muscle actin expression, and type IV collagen
      accumulation. These data indicate that ICAM-1 is a central mediator of glomerular
      and tubulointerstitial injury in murine nephrotoxic nephritis.

PMID- 9773780
TI  - Effects of smoking on renal hemodynamics in healthy volunteers and in patients
      with glomerular disease.
AB  - Patients with renal disease who smoke have a poor renal functional prognosis, but
      the mechanisms involved have not been explored. In this controlled study, the
      effects of smoking and sham smoking were compared in 15 healthy normotensive
      volunteers. All were occasional smokers and abstained from smoking for 48 h as
      documented by urinary cotinine measurements. These data were compared with those
      of seven patients with biopsy-confirmed IgA glomerulonephritis, also occasional
      smokers. Renal clearance examinations were obtained after hydration in the supine
      position before and while smoking two cigarettes or sham cigarettes in random
      order on 2 consecutive days. GFR and effective renal plasma flow were determined
      using In111-diethylenetriamine penta-acetic acid and 131I-hippurate with a dual
      tracer infusion clearance technique. In an ancillary study with six volunteers,
      the effect of smoking was compared with the effect of nicotine-containing chewing
      gum. In healthy volunteers, sham smoking caused a minor but significant increase
      of mean arterial pressure (MAP) and GFR with no significant change of effective
      renal plasma flow, filtration fraction (FF), or renovascular resistance. Smoking
      caused a significant and more marked increase of MAP (from baseline 92.8+/-8.98
      to 105+/-7.78 mmHg) and heart rate (from 61.7+/-7.52 to 86.4+/-9.87 min(-1)),
      accompanied by a significant increase in arginine vasopressin (from 1.27+/-0.72
      to 19.9+/-27.2 pg/ml) and epinephrine (from 37+/-13 to 140+/-129 pg/ml). During
      smoking, GFR decreased in all but one volunteer (from 120+/-17.7 to 102+/-19.3
      ml/min per 1.73 m2), and this was accompanied by a significant decrease of FF
      (from 21.3+/-4.24 to 17.4+/-3.41%) and an increase in renovascular resistance
      (from 97.6+/-27.2 to 108+/-30.4 mmHg x min/ml per 1.73 m2). These findings were
      reproduced with nicotine-containing chewing gum. In contrast, when patients with
      IgA glomerulonephritis smoked, a similar increment in MAP was noted, the changes
      of FF were not uniform, and a small but consistent increase of urinary
      albumin/creatinine ratio was observed. An additional 20 volunteers were subjected
      to the smoking arm of the study for statistical evaluation of the GFR change in
      patients. The difference between the change of GFR between all volunteers (n =
      35) and patients (n = 7) was significant (P < 0.005). It is concluded that the
      known effects of smoking and nicotine on the sympathetic nervous system and on
      systemic hemodynamics are accompanied by significant acute changes in renal
      hemodynamics and albuminuria. These findings are of interest because of the known
      effects of smoking on progression of renal disease.

PMID- 9773782
TI  - Activated mesangial cells produce vascular permeability factor in early-stage
      mesangial proliferative glomerulonephritis.
AB  - Vascular permeability factor (VPF), also known as vascular endothelial growth
      factor (VEGF), is a multifunctional cytokine involved in angiogenesis,
      inflammation, and wound healing. Although VPF/VEGF has been reported to be
      produced only by glomerular podocytes in glomeruli, it was found that it is
      produced by human cultured mesangial cells (MC). Therefore, immunohistochemical
      analysis (using indirect immunofluorescence and in situ hybridization) of
      VPF/VEGF in normal kidneys (n = 7) and biopsy specimens taken from 83 patients
      with renal diseases, including mesangial proliferative glomerulonephritis (PGN)
      (n = 58), was performed to examine whether VPF/VEGF is produced by MC in human
      PGN. In all of the healthy subjects and all of the patients except those with PGN
      (disease control subjects), VPF/VEGF protein and mRNA were detected mainly in
      podocytes. However, in some PGN patients, VPF/VEGF protein was demonstrated
      clearly in MC as well as in podocytes, as some of the VPF/VEGF was colocalized
      with alpha-smooth muscle actin, a marker of activated MC, and VPF/VEGF mRNA was
      expressed by MC and podocytes. Mesangial VPF/VEGF expression level increased
      significantly in PGN patients with early lesions (P < 0.01 versus healthy
      subjects or disease control subjects, P < 0.05 versus PGN with later lesions).
      The time between biopsy and disease onset was significantly shorter in PGN
      patients with than in those without mesangial VPF/VEGF expression (P < 0.01).
      These findings provide the first evidence that activated MC are a source of
      VPF/VEGF in human PGN, and indicate that mesangial VPF/VEGF expression is
      characteristic of early lesions of PGN. Because VPF/ VEGF plays a pivotal role in
      tissue repair, MC-produced VPF/VEGF may play pathophysiologic roles, including
      promoting recovery from glomerular injuries, in early-stage PGN.

PMID- 9773783
TI  - Inhibition of calcitriol-induced monocyte CD14 expression by uremic toxins: role
      of purines.
AB  - End-stage renal disease is associated with a defect in immunologic functions.
      Previous studies have demonstrated that uremic ultrafiltrate (UUF) contains
      factors that suppress calcitriol synthesis and its biological actions. In the
      present study, the effect of UUF on basal and calcitriol-induced membrane bound
      CD14 expression of monocytes activated by phorbol 12-myristate 13-acetate was
      evaluated. CD14 acts as a receptor for the complexes of lipopolysaccharide and
      lipopolysaccharide-binding protein. Monocytes isolated from normal donors were
      used for the assay of monocyte CD14 expression. A calcitriol induced rise in
      monocyte CD14 expression (1966+/-423 to 2421+/-436 fluorescence intensity) was
      found. However, UUF not only suppressed basal CD14 expression of monocytes (from
      1966+/-423 to 1240+/-203, P < 0.05) but also significantly blunted calcitriol
      induced CD14 expression (from 2421+/-436 to 1744+/-229, P < 0.05). HPLC
      fractionated UUF collected from 8 to 16 min (fraction 1, F1) and from 25 to 40
      min (fraction 3, F3) also significantly suppressed the expression of CD14.
      Because purine derivatives coeluted within F1, their effect on monocyte CD14
      expression was also tested. Uric acid, xanthine, and hypoxanthine was found to
      suppress basal as well as calcitriol-induced CD14 expression of monocytes in a
      dose-dependent manner. In conclusion, UUF contains factors that impair calcitriol
      activated function of monocytes.

PMID- 9773784
TI  - Altered instantaneous and calcium-modulated oscillatory PTH secretion patterns in
      patients with secondary hyperparathyroidism.
AB  - The relative contributions of increased parathyroid cell mass and altered control
      mechanisms of parathyroid hormone (PTH) secretion in secondary
      hyperparathyroidism are still controversial. In this study, endogenous pulsatile
      PTH secretion was analyzed by the multiparameter deconvolution technique to
      differentiate alterations in cell mass-dependent (PTH burst mass) and regulation
      dependent (frequency, synchrony, calcium responsiveness) PTH release in uremic
      patients. PTH concentration versus time profiles were obtained in 13 uremic and
      16 healthy adults under baseline conditions and during acute hypo- and
      hypercalcemia. Plasma PTH half-life was increased in patients compared with
      control subjects (4.7+/-1.9 versus 2.6+/-0.1 min, P < 0.005). The baseline PTH
      secretion rate was elevated eightfold in the patients as a result of an increased
      PTH mass secreted per burst (17.1+/-4.7 versus 2.0+/-0.4 pM, P = 0.0001), higher
      burst frequency (8.0+/-0.3 versus 6.8+/-0.3 h(-1), P < 0.01), and a higher tonic
      secretion rate (343+/-99 versus 30+/-4 pM/h, P = 0.0001). Acute hypocalcemia
      elicited an immediate, frequency- and amplitude-mediated selective increase in
      the pulsatile secretory component, which was fractionally weaker in patients
      (+595%) than control subjects (+1755%, P < 0.001). The acceleration and the
      amplification of PTH bursts were 35 and 60% lower in the patient group. Acute
      hypercalcemia suppressed total PTH secretion by 79% in control subjects but only
      by 63% in patients (P < 0.002). PTH burst frequency was reduced during
      hypercalcemia by 30% in control subjects, but remained unchanged in patients. In
      conclusion, uremic hyperparathyroidism is mediated by a marked increase in
      glandular secretion, but also by reduced PTH elimination. The increased
      spontaneous PTH burst frequency and the blunted responsiveness to changes in Ca2+
      indicate partial uncoupling of hyperplastic parathyroid glands from the
      physiologic regulatory mechanisms that direct pulsatile PTH release.

PMID- 9773785
TI  - High phosphate level directly stimulates parathyroid hormone secretion and
      synthesis by human parathyroid tissue in vitro.
AB  - Phosphate retention plays an important role in the pathogenesis of secondary
      hyperparathyroidism in patients with renal failure. In in vitro studies, high
      extracellular phosphate levels directly stimulate PTH secretion in rat and bovine
      parathyroid tissue. The present study evaluates the effect of high phosphate
      levels on the secretion of PTH and the production of prepro PTH mRNA in human
      hyperplastic parathyroid glands. The study includes parathyroid glands obtained
      from patients with primary adenomas and from hemodialysis and kidney-transplant
      patients with diffuse and nodular secondary hyperplasia. The experiments were
      performed in vitro using small pieces of parathyroid tissue. The ability of high
      calcium levels to decrease PTH secretion was less in adenomas than in secondary
      hyperplasia; among the secondary hyperplasia, nodular was less responsive to an
      increase in calcium than diffuse hyperplasia. In diffuse hyperplasia, PTH
      secretion was increased in response to 3 and 4 mM phosphate compared with 2 mM
      phosphate, despite a high calcium concentration in the medium; prepro PTH mRNA
      levels increased after incubation in 4 mM phosphate. Similar results were
      obtained with nodular hyperplasia, except that the elevation of PTH secretion in
      response to 3 mM phosphate did not attain statistical significance. In adenomas,
      high calcium concentrations (1.5 mM) did not result in inhibition of PTH
      secretion, independent of the phosphate concentration, and the prepro PTH mRNA
      was not significantly increased by high phosphate levels. In conclusion, first,
      the PTH secretory response to an increase in calcium concentration is less in
      nodular than diffuse hyperplasia; second, high phosphate levels directly affect
      PTH secretion and gene expression in patients with advanced secondary
      hyperparathyroidism.

PMID- 9773786
TI  - A spectrum of mutations in the polycystic kidney disease-2 (PKD2) gene from eight
      Canadian kindreds.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a common Mendelian
      disorder that affects approximately 1 in 1000 live births. Linkage studies have
      shown that the majority (approximately 85%) of cases are due to mutations in PKD1
      on chromosome 16p, while mutations in PKD2 on chromosome 4q account for most of
      the remaining cases. Locus heterogeneity in ADPKD is known to contribute to
      differences in disease severity, with PKD1-linked families having earlier onset
      of end-stage renal disease (ESRD) than PKD2-linked families (mean age at ESRD: 56
      versus 70, respectively). In this study, 11 Canadian families with ADPKD were
      screened for PKD2 mutations. In four families, linkage to PKD2 was previously
      documented. In the remaining seven smaller families, one or more affected members
      had late-onset ESRD at age 70 or older. Using single-stranded conformational
      polymorphism analysis, one affected member from each family was screened for
      mutations in all 15 exons of PKD2, which were PCR-amplified from genomic
      templates. A spectrum of mutations was found in approximately 73% (8 of 11) of
      the families screened, with no difference in the detection rate between the PKD2
      linked families and the families with late-onset ESRD. In three unrelated
      families, insertion or deletion of an adenosine in a polyadenosine tract (i.e.,
      (A)8 at nt 2152-2159) was found on exon 11, suggesting that this mononucleotide
      repeat tract is prone to mutations from "slipped strand mispairing." All
      mutations, scattered between exons 1 and 11, are predicted to result in a
      truncated polycystin 2 that lacks both the calcium-binding EF-hand domain and the
      two cytoplasmic domains required for the interaction of polycystin 2 with
      polycystin 1 and with itself. Furthermore, no correlation was found between the
      location of the mutations in the PKD2 coding sequence and disease severity. Thus,
      these findings are consistent with other recently published reports and suggest
      that most PKD2 mutations are inactivating.

PMID- 9773787
TI  - Functional studies of twelve mutant V2 vasopressin receptors related to
      nephrogenic diabetes insipidus: molecular basis of a mild clinical phenotype.
AB  - X-linked nephrogenic diabetes insipidus (NDI) is a rare disease with defective
      renal and extrarenal arginine vasopressin V2 receptor responses due to mutations
      in the AVPR2 gene in Xq28. To study the cause of loss of function of mutant V2
      receptors, we expressed 12 mutations (N55H, L59P, L83Q, V88M, 497CC-->GG,
      deltaR202, I209F, 700delC, 908insT, A294P, P322H, P322S) in COS-7 cells. Eleven
      of these, including P322H, were characterized by a complete loss of function, but
      the mutation P322S demonstrated a mild clinical and in vitro phenotype. This was
      characterized by a late diagnosis without any growth or developmental delay and a
      significant increase in urine osmolality after intravenous 1-deamino[D-Arg8]AVP
      administration. In vitro, the P322S mutant was able to partially activate the
      Gs/adenylyl cyclase system in contrast to the other V2R mutants including P322H,
      which were completely inactive in this regard. This showed not only that Pro 322
      is important for proper V2R coupling, but also that the degree of impairment is
      strongly dependent on the identity of the substituting amino acid. Three
      dimensional modeling of the P322H and P322S mutant receptors suggested that the
      complete loss of function of the P322H receptor could be due, in part, to
      hydrogen bond formation between the His 322 side chain and the carboxyl group of
      Asp 85, which does not occur in the P322S receptor.

PMID- 9773788
TI  - Expression of SET, an inhibitor of protein phosphatase 2A, in renal development
      and Wilms' tumor.
AB  - The human gene set was originally identified as a component of the set-can fusion
      gene produced by a somatic translocation event in a case of acute
      undifferentiated leukemia. In the developing kidney, set was highly expressed in
      the zone of nephron morphogenesis. Recently, SET was shown to be a potent and
      specific inhibitor of protein phosphatase 2A, a family of major serine/threonine
      phosphatases involved in regulating cell proliferation and differentiation. The
      current study sought to define further the role of SET in the regulation of renal
      cell proliferation and tumorigenesis. The mRNA encoding SET was expressed at much
      higher levels in transformed human and rodent cell lines than in cultured renal
      epithelial and primary endothelial cells. Consistent with a role for SET in cell
      proliferation, set mRNA expression was markedly reduced in cells rendered
      quiescent by serum starvation, contact inhibition, or differentiation. Previous
      findings during renal development were extended by demonstrating that SET protein
      expression is also much greater in developing rat and human kidney than in fully
      differentiated, mature kidney. Finally, high levels of set mRNA and SET protein
      expression were found in Wilms' tumor, but not in renal cell carcinoma, adult
      polycystic kidney disease or in transitional cell carcinoma.

PMID- 9773789
TI  - Differential effects of antibodies to vascular cell adhesion molecule-1 and
      distinct epitopes of the alpha4 integrin in HgCl2-induced nephritis in Brown
      Norway rats.
AB  - Four distinct epitopes (A, B1, B2, and C) have been functionally defined on the
      human alpha4 integrin. In this study, two cross-reactive antihuman alpha4
      monoclonal antibodies (mAb) (HP2/1 and HP2/4 specific for epitopes B1 and B2,
      respectively) were used to functionally characterize the rat VLA-4 subunit and to
      define similar functional epitopes in this rodent species. It was found that B1
      and B2 anti-alpha4 mAb completely block adhesion to fibronectin, but the
      inhibition of adhesion to vascular cell adhesion molecule-1 (VCAM-1) with HP2/1
      mAb was lower than with HP2/4 mAb. It was also observed that epitope B2 HP2/4 mAb
      induced homotypic aggregation in rat lymphocytes, whereas epitope B1 HP2/1 mAb
      did not. Using the HgCl2 model of nephritis, this study shows the protective
      effect of both anti-alpha4 mAb against infiltration of the renal interstitium by
      leukocytes. Nevertheless, HP2/1 mAb, but not HP2/4 mAb, virtually abolished the
      anti-glomerular basement membrane antibody synthesis and glomerular deposits.
      These findings indicate the dual but independent role played by alpha4 integrins
      in both extravasation of leukocytes and in the production of antibodies. Finally,
      this study demonstrates that anti-rat VCAM-1 mAb showed a positive reactivity of
      the renal vascular endothelium and, most importantly, that administration of anti
      VCAM-1 antibodies completely abrogated the interstitial cell infiltrates without
      affecting anti-glomerular basement membrane antibody production. These results
      confirm the important role played by VLA-4/VCAM-1 pathway in leukocyte
      infiltration, and further support the dual and independent role of alpha4
      integrins in both renal infiltration and autoantibody synthesis in this model of
      renal disease.

PMID- 9773790
TI  - Tissue-specific responses of branched-chain alpha-ketoacid dehydrogenase activity
      in metabolic acidosis.
AB  - In adrenalectomized rats, acidosis does not increase whole-body leucine oxidation
      unless a physiologic amount of glucocorticoids (dexamethasone) is also provided;
      an equivalent dose of dexamethasone without acidosis does not change leucine
      catabolism. Because the influences of acidification and glucocorticoids on
      branched-chain amino acid metabolism in specific organs are unknown, the function
      of branched-chain alpha-ketoacid dehydrogenase (BCKAD), the rate-limiting enzyme
      in branched-chain amino acid catabolism, in adrenalectomized rat skeletal muscle
      and liver, the two major tissues that degrade branched-chain amino acid was
      measured. In muscle of acidotic adrenalectomized rats receiving dexamethasone,
      basal and total BCKAD activities were increased 2.6- (P < 0.05) and 2.8-fold (P <
      0.05), respectively. Neither acidosis nor dexamethasone alone increased these
      activities. BCKAD E1alpha subunit mRNA in muscle of acidotic rats given
      dexamethasone was increased 1.89-fold (P < 0.05) in parallel with the change in
      BCKAD activity; BCKAD E2 subunit mRNA was increased by acidosis, dexamethasone,
      or a combination of both stimuli. In contrast, basal BCKAD activity in liver of
      rats with acidosis or dexamethasone was nearly threefold lower (P < 0.05) and
      changes in enzyme activity reflected reduced subunit mRNA. Thus, there are
      reciprocal, tissue-specific changes in BCKAD function in response to acidosis.

PMID- 9773791
TI  - Factors predictive of the short- and long-term efficacy of growth hormone
      treatment in prepubertal children with chronic renal failure. The German Study
      Group for Growth Hormone Treatment in Chronic Renal Failure.
AB  - To evaluate the growth-stimulating effects of short- and long-term treatment with
      recombinant human growth hormone (rhGH) in growth-retarded children with chronic
      renal failure (CRF), 103 prepubertal children with CRF on conservative treatment
      (n = 74) or dialysis (n = 29) were treated with rhGH for up to 5 yr. rhGH
      treatment persistently increased standardized height (+ 1.6 SD scores) and
      predicted adult height (+7.7 cm, Tanner method) during the first 3 treatment
      years (P < 0.001 versus baseline), followed by percentile parallel growth during
      continued treatment. Both standardized height and predicted adult height were
      significantly more increased in conservatively treated than in dialyzed children
      (P < 0.001). Age, GFR, target height, and prestudy growth rate were identified as
      independent predictors of the response to rhGH treatment during the first and
      second treatment year. GFR and target height were positively correlated with the
      change in height SD score and the change in absolute or age-standardized height
      velocity. Age affected the growth response depending on which outcome measure was
      used: Although the first-year change in height SD score was inversely correlated
      with age, the change in absolute height velocity was independent of age, and the
      change in standardized height velocity was positively correlated with age. The
      growth response during the first treatment year positively predicted the long
      term response. In conclusion, the short- and long-term growth response to rhGH
      treatment in prepubertal growth-retarded children with CRF is significantly
      affected by age, GFR, target height, and the pretreatment growth rate. Therefore,
      rhGH should be preferably started at a young age, and early in the course of CRF.

PMID- 9773792
TI  - Factors relating to urinary protein excretion in children with autosomal dominant
      polycystic kidney disease.
AB  - Adults with autosomal dominant polycystic kidney disease (ADPKD) who have overt
      proteinuria (>300 mg/d) have higher mean arterial pressures, lower creatinine
      clearances, larger renal volumes, and a more aggressive course of renal disease
      than ADPKD patients without proteinuria. This study examines the relationship
      between proteinuria and microalbuminuria and similar factors in ADPKD children. A
      total of 189 children from 81 ADPKD families was included in the analysis. The
      ADPKD children (n = 103) had significantly greater urine protein excretion rates
      than the non-ADPKD children (n = 86) (3.9+/-0.3 versus 2.8+/-0.2 mg/m2 per h, P <
      0.001). Children with severe renal cystic disease (> 10 cysts; n = 54) had
      greater protein excretion than those with moderate disease (< or = 10 cysts; n =
      49) (4.4+/-0.5 versus 3.3+/-0.2 mg/m2 per h, P < 0.05). The ADPKD children had
      significantly greater albumin excretion rates than the non-ADPKD children (32+/-6
      versus 10+/-2 mg/m2 per 24 h, P < 0.001), and a higher percentage of ADPKD
      children had significant microalbuminuria (>15 mg/m2 per 24 h in boys and >23
      mg/m2 per 24 h in girls) than their unaffected siblings (30% versus 10%, P <
      0.05). Thirty percent of ADPKD children had albuminuria and 23% had overt
      proteinuria. For all ADPKD children, there was no correlation between proteinuria
      and hypertension. However, there was a significant correlation between urinary
      protein excretion and diastolic BP among children diagnosed after the first year
      of life (r = 0.23, P < 0.05). Therefore, proteinuria and albuminuria occur early
      in the course of ADPKD and may be markers of more severe renal disease.

PMID- 9773793
TI  - Determinants of renal outcome in anti-myeloperoxidase-associated necrotizing
      crescentic glomerulonephritis.
AB  - Patients with anti-myeloperoxidase (MPO)-associated necrotizing crescentic
      glomerulonephritis (NCGN) may develop chronic renal failure (CRF) leading to end
      stage renal disease despite an initially favorable response to treatment. The aim
      of this study was to determine the prognostic value of clinical, laboratory, and
      histopathologic features at the time of presentation and during follow-up for the
      development of CRF in 21 consecutive anti-MPO-positive patients with NCGN. Renal
      function did not recover in two of five patients who were dialysis-dependent at
      presentation. The remaining 19 patients all went into remission and were off
      dialysis at 3 mo after diagnosis. At long-term follow-up, nine of these patients
      had stable renal function and did not relapse (group A), five patients developed
      CRF without signs of relapse (group B), and five patients relapsed (group C). At
      diagnosis, serum creatinine, C-reactive protein, and anti-MPO levels did not
      differ between groups A, B, and C. Microscopic erythrocyturia resolved in all
      patients within 4 mo of treatment. BP at presentation and during follow-up did
      not differ between groups A, B, and C. Proteinuria at diagnosis and in the first
      6 mo after diagnosis was higher in patients who developed CRF than in patients
      with a stable renal function. Anti-MPO levels at 3 mo had decreased compared with
      anti-MPO levels at diagnosis in groups A and C, whereas anti-MPO levels did not
      fall significantly in patients who developed CRF. The predictive value of a renal
      biopsy at diagnosis on long-term renal outcome was limited. In conclusion, a
      higher degree of proteinuria at diagnosis and during follow-up as well as
      persistently elevated anti-MPO levels after induction of remission are associated
      with the development of CRF and are predictive of poor renal outcome in anti-MPO
      associated NCGN.

PMID- 9773795
TI  - Longitudinal lipid profiles on CAPD: their relationship to weight gain,
      comorbidity, and dialysis factors.
AB  - The dyslipidemia of chronic renal failure may worsen after the commencement of
      continuous ambulatory peritoneal dialysis (CAPD). The purpose of this study was
      to relate baseline and longitudinal changes in the lipid profile to
      anthropometrics (weight, mid-arm circumference), aspects of treatment (albumin,
      total protein losses, peritoneal solute transport [dialysate:plasma ratio of
      creatinine], dialysate caloric load), total calorie intake (cal/kg), preexisting
      cardiovascular comorbidity, and survival. Lipid profiles (triglycerides [TG],
      total cholesterol [TC], and HDL) were measured, along with the above factors,
      every 6 mo in an unselected prospective cohort of 124 patients who were not
      treated with lipid-lowering drugs, commencing CAPD between 1990 and 1993, until
      1995. On univariate analysis, age, plasma albumin, cardiovascular disease,
      baseline TG, and TC:HDL ratio predicted survival. Simultaneous multiple Cox
      regression including all of the significant predictors demonstrated that either
      high TG or TC: HDL still predicted death, both in patients with and without
      clinically overt cardiovascular disease. Between 6 and 36 mo of treatment, TC,
      TG, and TC:HDL were elevated when compared with the baseline, more so in patients
      with preexisting cardiovascular disease (P < 0.05). Throughout this period,
      weight and mid-arm circumference correlated positively with TG and negatively
      with HDL. There were positive correlations between TC and albumin levels for 12
      mo after commencement of treatment, but otherwise there were no significant or
      consistent relationships between lipid profiles and total protein losses,
      dialysate calorie load, or total cal/kg or solute transport. The worsening
      dyslipidemia associated with CAPD was not associated with aspects of treatment
      such as glucose load or protein losses. The strongest predictors of worsening
      lipid profiles were weight gain and preexisting cardiovascular comorbidity.

PMID- 9773794
TI  - Effect of single dose resin-cathartic therapy on serum potassium concentration in
      patients with end-stage renal disease.
AB  - Hyperkalemia in patients with renal failure is frequently treated with a cation
      exchange resin (sodium polystyrene sulfonate, hereafter referred to as resin) in
      combination with a cathartic, but the effect of such therapy on serum potassium
      concentration has not been established. This study evaluates the effect of four
      single-dose resin-cathartic regimens and placebo on 5 different test days in six
      patients with chronic renal failure. Dietary intake was controlled. Fecal
      potassium output and serum potassium concentration were measured for 12 h.
      Phenolphthalein alone caused an average fecal potassium output of 54 mEq. The
      addition of resin caused an increase in insoluble potassium output but a decrease
      in soluble potassium output; therefore, there was no significant effect of resin
      on total potassium output. Sorbitol plus resin caused less potassium output than
      phenolphthalein plus resin. On placebo therapy, the average serum potassium
      concentration increased slightly (0.4 mEq/L) during the 12-h experiment. This
      rise was apparently abrogated by some of the regimens that included resin; this
      may have been due in part to extracellular volume expansion caused by absorption
      of sodium released from resin. Phenolphthalein regimens were associated with a
      slight rise in serum potassium concentrations (similar to placebo); this may have
      been due to extracellular volume contraction produced by high volume and sodium
      rich diarrhea and acidosis secondary to bicarbonate losses. None of the regimens
      reduced serum potassium concentrations, compared with baseline levels. Because
      single-dose resin-cathartic therapy produces no or only trivial reductions in
      serum potassium concentration, and because this therapy is unpleasant and
      occasionally is associated with serious complications, this study questions the
      wisdom of its use in the management of acute hyperkalemic episodes.

PMID- 9773796
TI  - Mortality in end-stage renal disease is associated with facility-to-facility
      differences in adequacy of hemodialysis.
AB  - Death rates of end-stage renal disease (ESRD) patients treated with hemodialysis
      vary substantially among treatment centers. The association between facility-to
      facility differences in delivered hemodialysis dose and facility-specific
      mortality rates was examined among 5817 randomly selected patients treated with
      hemodialysis on October 1, 1994, from all 213 hemodialysis treatment centers
      reporting to ESRD Network 6. The mean urea reduction ratio (URR) for each
      treatment center, a measure of hemodialysis adequacy, was calculated for each
      facility, using measurements made by center staff members during one treatment
      for each of the randomly selected patients. During 7 mo of follow-up (ending
      April 30, 1995), 441 (7.6%) patients died. The average URR among the treatment
      centers was 64.9%. There was a strong, inverse association between increasing
      treatment center URR and adjusted mortality count (P = 0.009). Other treatment
      center characteristics associated with increased mortality included free-standing
      status (P = 0.009) and decreasing frequency of reported physician supervision of
      care (P = 0.01). It was concluded that lower average levels of dialysis adequacy
      in treatment centers are associated with higher rates of death, and this
      association persists after controlling for facility-to-facility differences in
      patient and nonpatient characteristics.

PMID- 9773798
TI  - Peritonitis as a complication of peritoneal dialysis.

PMID- 9773797
TI  - Chronic allograft nephropathy in the rat is improved by angiotensin II receptor
      blockade but not by calcium channel antagonism.
AB  - Functional and structural changes of chronic renal allograft failure share
      similarities with other chronic nephropathies with low nephron number. In models
      of reduced nephron number, angiotensin-converting enzyme inhibitors or
      angiotensin II receptor blockers prevented proteinuria and retarded renal
      lesions. This study investigates whether blockade of angiotensin II activity
      prevented chronic allograft injury in the Fisher 344 --> Lewis rat kidney
      transplant model, and compares its effect with that of calcium channel blockers,
      the main antihypertensive agents used in transplant patients to control BP.
      Transplanted rats received either no treatment (control), the type 1 angiotensin
      II receptor antagonist losartan, or the calcium channel blocker lacidipine. Rats
      received cyclosporine for the first 10 d posttransplant to prevent acute
      rejection. Doses of antihypertensive drugs were adjusted to achieve a comparable
      level of BP control throughout the study. Awake systolic BP was comparable in
      animals given losartan or lacidipine during the 6-mo observation period. Daily
      treatment with losartan but not lacidipine resulted in a significant decrease in
      the amount of proteinuria, preserved glomerular and tubulointerstitial structure,
      and improved graft survival compared with corresponding parameters in control
      untreated rats. GFR, measured as inulin and p-aminohippurate clearances,
      respectively, in rats surviving the 6-mo follow-up, was numerically but not
      significantly higher in losartan-treated animals than in all other groups. Thus,
      at comparable levels of BP control, losartan but not lacidipine effectively
      protects animals from chronic allograft injury and allows long-term survival.

PMID- 9773799
TI  - Composition of fluid in twelve cysts of a polycystic kidney. 1969.

PMID- 9773800
TI  - Tamoxifen as a potential treatment of glioma.
AB  - Cerebral gliomas have a poor survival time even after multimodal treatment,
      because of the unavoidable recurrence of tumor. Several trials with a combination
      of old and new chemotherapics have been performed, but survival time remains
      generally less than 12 months. Tamoxifen (TAM) has recently been shown to inhibit
      the growth rate of established and low-passage human glioma cell lines.
      Furthermore, this drug has enabled stabilization of the clinical and radiographic
      picture in selected patients with recurrent glioma. Here we review published data
      to discuss a potential role of TAM in the multimodal postoperative treatment of
      cerebral gliomas.

PMID- 9773801
TI  - O-glucuronidation, a newly identified metabolic pathway for topotecan and N
      desmethyl topotecan.
AB  - During topotecan analysis of clinical urine samples, an additional peak eluting
      just after the solvent front was observed. This potential metabolite was isolated
      by chromatographic methods. Mass spectrometry data along with chromatographic
      retention data and fluorescence characteristics showed that the isolated
      fractions contained two compounds, i.e. topotecan-O-glucuronide and N-desmethyl
      topotecan-O-glucuronide. The concentrations of the metabolites in human urine
      were relatively low. When topotecan was given as a 30 min infusion at a dosage of
      1.5 mg/m2 daily for five consecutive days every 3 weeks, the maximal metabolite
      concentrations in a 24 h urine sample were approximately 10% of topotecan-O
      glucuronide and 3.5% of N-desmethyl topotecan-O-glucuronide with respect to the
      concentration of topotecan in the urine. This is the first report demonstrating
      that glucuronide metabolites of topotecan are present in the urine of treated
      patients.

PMID- 9773802
TI  - A multicenter, double-blind comparison of i.v. and oral administration of
      ondansetron plus dexamethasone for acute cisplatin-induced emesis. Ondansetron
      Acute Emesis Study Group.
AB  - A total of 530 patients were treated in this multicenter, double-blind, double
      dummy, parallel group study to compare the anti-emetic efficacy and safety of a
      once daily ondansetron oral regimen with a once daily i.v. dosing regimen over a
      24 h period, administered to patients prior to receiving cisplatin (50 mg/m2 or
      greater) chemotherapy. Patients were randomized to receive a single dose of
      ondansetron plus dexamethasone given either orally (ondansetron 24 mg and
      dexamethasone 12 mg, n=262) or i.v. (ondansetron 8 mg and dexamethasone 20 mg,
      n=268). Complete control of emesis (i.e. no emetic episodes, no rescue and no
      premature withdrawal) was achieved for 85% of patients (224 of 262) in the oral
      group and 83% (223 of 268) in the i.v. group. No nausea was reported in 70% of
      patients in the oral group and 68% in the i.v. group. There were no statistically
      significant differences between the two groups for any of the assessments of
      efficacy, which included time to first emetic episode, number of emetic episodes
      and the worst grade of nausea occurring over the 24 h study period. Once daily
      ondansetron oral and i.v., in combination with dexamethasone, was well tolerated
      in this study. In conclusion, once daily oral ondansetron 24 mg plus
      dexamethasone is equally effective in the control of emesis and nausea induced by
      highly emetogenic chemotherapy as once daily ondansetron 8 mg i.v. plus
      dexamethasone.

PMID- 9773804
TI  - Synthesis and biological activity of gold and tin compounds in ovarian cancer
      cells.
AB  - We have investigated the patterns of in vitro cytotoxicity, induced by six newly
      synthesized gold and tin compounds, in three human ovarian cancer cell lines (SW
      626, IGROV 1 and OVCAR-3). Four gold compounds, i.e. gold(I)lupinylsulfide
      hydrochloride [1] (containing a naked gold atom),
      triethylphosphinogold(I)lupinylsulfide hydrochloride [2], triphenyl
      phosphinogold(I)lupinylsulfide hydrochloride [3] and 1 ,2
      bis(diphenylphosphino)ethane bis[gold(I)lupinylsulfide] dihydrochloride [4] (all
      containing a gold atom coordinated with different phosphines), were prepared.
      Moreover, the triethylphosphinogold(I)(2-diethylamino)ethylsulfide hydrochloride
      [5] in which the simple diethylaminoethylthiol replaced the bulky lupinylthiol
      was synthesized. The tin compound, triethyltin(IV)lupinylsulfide hydrochlorlde
      [6], was also studied. Comparative tests with cisplatin, the most widely used
      antitumor agent in ovarian cancer, were carried out in biological Investigations.
      In vitro cytotoxicity, by MTT assay, showed that compound [4] and compound [6]
      exhibited interesting antiproliferative activity in all the three cell lines
      (mean IC50=1.3 and 0.7 microM, respectively) compared to cisplatin (mean IC50=4.8
      microM). In addition, the PA-1 cell line, more sensitive to cisplatin (IC50=0.6
      microM), was included as a comparison in the study. Cell count assays confirmed
      the cytotoxic properties of compounds [4] and [6] against the four cell lines,
      reporting higher growth Inhibition potency than cisplatin, with IC50 values in
      the sub-micromolar range.

PMID- 9773803
TI  - Results of leucovorin and doxifluridine oral regimen in the treatment of
      metastatic colorectal cancer.
AB  - We conducted a multicentric phase II study on advanced colorectal cancer to
      determine the efficacy and toxicity of oral treatment with leucovorin (LV) plus
      doxifluridine (5'DFUR), a novel fluoropyrimidine derivative with proven antitumor
      activity in different experimental models. Thirty-six outpatients with measurable
      disease entered the trial and received orally LV 20 mg in the morning and in the
      afternoon, and 2 h later 5'-DFUR 500 mg/m2 every 2 days for 3 months. Thirty-four
      evaluable patients underwent a total of 408 weeks of treatment. The response rate
      was 35%, with two complete remissions and 10 partial responses. The median
      survival of patients who responded to treatment (responders) was 17.1 months
      (range 4-32), which was significantly longer (p<0.001) than the 6.5 months (range
      2-11) of the patients who did not respond (non-responders). Therefore, after 4-8
      weeks of treatment, 14 patients (41%) had an improvement in their performance
      status and/or stabilization of pain. General toxicity was usually mild, myelo and
      gastrointestinal toxicity were moderate, and there was no evidence of relevant
      neurological toxicity. These results show that a home therapy with oral LV-5'DFUR
      is a safe and effective treatment regimen for metastatic colorectal carcinoma.

PMID- 9773805
TI  - Phase I trial of a 96 h paclitaxel infusion with filgrastim support in refractory
      solid tumor patients.
AB  - A phase I study of a 96 h paclitaxel infusion with filgrastim support was
      performed to determine the toxicity, maximum-tolerated dose (MTD) and
      pharmacokinetics in patients with refractory solid tumors. In this phase I trial,
      the initial paclitaxel dose was 140 mg/m2/96 h followed by filgrastim (5
      microg/kg/day s.c.) beginning 24 h after the paclitaxel and continued until
      granulocyte recovery. Cycles were repeated every 21 days. Patients with
      refractory solid tumors were eligible; however, only one previous chemotherapy
      regimen was allowed. The dose of paclitaxel was escalated by 20 mg/m2/96 h in
      subsequent cohorts until dose-limiting toxicity (DLT) occurred. Pharmacokinetic
      analysis was performed by quantitating paclitaxel concentrations at baseline, 24,
      48, 72 and 96 h after the start of the paclitaxel infusion. Twenty-one patients
      were entered into this trial of which 19 were evaluable. A total of 52 treatment
      cycles were administered. DLT was seen in two of four patients at 200 mg/m2/96 h,
      and consisted of diarrhea, mucositis and granulocytopenic infection. The MTD of
      the 96 h paclitaxel infusion was 180 mg/m2 with filgrastim support. Mucosal and
      granulocyte toxicity were correlated with steady-state paclitaxel concentrations
      (Css) greater than 0.100 micromol/l. In the presence of liver function test 1.5
      times or lower than normal, metastatic liver disease did not alter paclitaxel
      Css. Objective responses were observed in non-small cell lung cancer, small cell
      lung cancer and melanoma. The recommended phase II dose of paclitaxel infused
      over 96 h with filgrastim support is 180 mg/m2. Paclitaxel Css correlate with
      mucosal and granulocyte toxicity. In the presence of normal enzymatic function,
      metastatic liver disease does not affect paclitaxel clearance.

PMID- 9773806
TI  - Gemcitabine after bone marrow transplantation for refractory juvenile granulosa
      cell tumor.
AB  - A 19-year-old woman with refractory juvenile granulosa cell tumors had persistent
      disease after PVB (cisplatin, vinblastine and bleomycin) and multiple high doses
      of ICE (ifosfamide, carboplatin and etoposide) with peripheral stem cell support.
      She achieved stable disease for 4 months with low dose intensity gemcitabine of
      500 mg/m2/week. The planned dose had been 1250 mg/m2/week. The dose intensity was
      limited by myelosuppression especially thrombocytopenia. The use of
      thrombopoietic, in addition to erythropoietic and myelopoietic, agents may permit
      higher dose intensity of gemcitabine after bone marrow ablative therapy with
      resulting greater anti-tumor activity.

PMID- 9773807
TI  - Comparison between short or long exposure to 5-fluorouracil in human gastric and
      colon cancer cell lines: biochemical mechanism of resistance.
AB  - Recent preclinical and clinical data indicate that the main mechanisms of 5
      fluorouracil (5-FU) cytotoxicity depend on the mode of administration. To gather
      further insight into the major causes of acquired 5-FU resistance, drug-sensitive
      human gastric (M2), colon (HT29) and breast (MCF7) cancer cell lines were
      repeatedly exposed to a fixed concentration of 5-FU given either for 1 or 24 h.
      Although equieffective doses (IC50) of 5-FU were used, resistance to a 1 h
      exposure of 5-FU developed faster in all models than to a 24 h exposure. Cell
      lines with acquired resistance to a 1 h application of 5-FU were only partly
      cross-resistant to a 24 h exposure, whereas lines with resistance to protracted
      application of 5-FU displayed significant cross-resistance to the 1 h schedule.
      Resistance to methotrexate was only seen in cell lines with acquired resistance
      to 24 h of 5-FU. All 5-FU-resistant cell lines showed reduced incorporation of 5
      FU into cellular RNA. Furthermore, elevations of thymidylate synthase were seen
      in all cell lines with resistance to 24 h of 5-FU but also in one cell line with
      resistance to a bolus schedule. No alterations in folylpolyglutamate synthase
      developed in the resistant cell lines. These data support the concept that the
      main mechanisms of 5-FU cytotoxicity depend on the mode of application.
      Incorporation of fluorouridine triphosphate into RNA appears to be the most
      important mechanism of action for 5-FU bolus schedules, whereas inhibition of
      thymidylate synthase becomes more important as the infusion time is prolonged.
      These data could have implications on the interaction of 5-FU given at different
      schedules with various other cytostatic agents.

PMID- 9773808
TI  - Mitoguazone induces apoptosis via a p53-independent mechanism.
AB  - Mitoguazone (methylglyoxal bisguanylhydrazone, methyl-GAG or MGBG) is a synthetic
      polycarbonyl derivative with activity in patients with Hodgkin's and non
      Hodgkin's lymphoma, head and neck cancer, prostate cancer, and esophageal cancer.
      Mitoguazone has also recently been documented to have activity in patients with
      AIDS-related lymphoma. Among anticancer drugs, mitoguazone has a unique mechanism
      of action via interference with the polyamine biosynthetic pathway. Polyamines
      stabilize DNA structure by non-covalent cross-bridging between phosphate groups
      on opposite strands. In addition, mitoguazone causes uncoupling of oxidative
      phosphorylation. In this study, the ability of mitoguazone to induce apoptosis by
      inhibiting the polyamine pathway was assessed in three Burkitt's lymphoma cell
      lines (Raji, Ramos and Daudi) and one prostate carcinoma cell line (MPC 3).
      Additional evaluations were performed in two human breast cancer cell lines (MCF7
      with wild-type p53 and VM4K with mutated p53) to determine whether the p53 tumor
      suppressor gene was required for efficient apoptosis induction. The present study
      demonstrated that mitoguazone induces apoptosis in all the different human cancer
      cell lines tested in a concentration- and time-dependent way, and triggers a p53
      independent programmed cell death in the human breast cancer MCF7 cell line.

PMID- 9773809
TI  - Synergistic cytotoxicity of topoisomerase I inhibitors with alkylating agents and
      etoposide in human brain tumor cell lines.
AB  - To evaluate potential synergistic interactions between topoisomerase I (Topo I)
      inhibitors, i.e. camptothecin (CPT) and topotecan (TPT), and chemotherapeutic
      agents known to be active in treatment of brain tumors, in vitro studies were
      conducted with human glioma and medulloblastoma cell lines. Tumor cells were
      exposed to CPT or TPT alone or in combination with cisplatin, 4
      hydroperoxycyclophosphamide (4-HC), BCNU or etoposide (VP-16). Cytotoxicity was
      assessed by colony formation assays. Drug interactions were evaluated by means of
      a novel analytical model which permits statistical evaluation over a range of
      dose combination. Experimental results were corroborated by published models of
      drug interaction. Our findings indicate that in vitro cytotoxic interactions in
      brain tumor cells between Topo I inhibitors and alkylating agents or etoposide
      depend on drug dose, dose schedule and tumor cell line. Treatment of DAOY
      medulloblastoma cells with CPT and either cisplatin, 4-HC or VP-16 produced
      significant synergistic cytotoxicity over a wide range of dose combinations. When
      VP-16 was administered after CPT, synergy was reduced to a narrow range of dose
      combinations. For U251 glioma cells, incubation with CPT and cisplatin or 4HC
      also produced synergistic cytotoxicity over a broad range of dose combinations.
      By contrast, antagonistic interactions were observed after administration of CPT
      with BCNU or VP-16. Treatment of U251 cells with CPT and cisplatin produced
      synergistic or antagonistic cytotoxicity depending on the dose combination used.
      These findings support a role for pharmacokinetic analysis in multiagent phase 11
      trials involving Topo I inhibitors and have important implications for clinical
      trial design strategies.

PMID- 9773810
TI  - The relationship between the antitumor activity and the ribonucleotide reductase
      inhibitory activity of (E)-2'-deoxy-2'-(fluoromethylene) cytidine, MDL 101,731.
AB  - (E)-2'-deoxy-2'-(fluoromethylene) cytidine (MDL101,731) is a new deoxycytidine
      analog which shows potent antitumor activity against several human tumor models.
      We previously showed that MDL101,731 inhibited human ribonucleotide reductase
      (RNR) in HeLa S3 human cervical carcinoma cells. Recently, it has been reported
      that another deoxycytidine analog, 2'-deoxy-2'-methylidenecytidine (DMDC) which
      also inhibits RNR from Escherichia coli, does not inhibit RNR in intact L1210
      murine leukemia cells. MDL101,731 was designed as an inhibitor of RNR, so it is
      important to know the contribution of the RNR inhibitory activity of the drug on
      its antitumor efficacy in vivo. Therefore, we examined the relationship between
      the antitumor activity and RNR inhibitory activity of MDL101,731 using LX-1 human
      lung carcinoma which was highly sensitive to this drug. MDL101,731 showed strong
      inhibition of RNR activity in LX-1 lung carcinoma by both i.v. and p.o.
      administration. Administration of 15 mg/kg i.v. and 30 mg/kg p.o. of MDL101,731,
      doses which showed almost the same degree of antitumor activity against LX-1 lung
      carcinoma on a daily 5 day schedule, caused a similar degree and similar kinetics
      of inhibition of RNR in LX-1 lung carcinoma at least for 12 h after
      administration. On the other hand, DMDC as well as 1-beta-D-arabinofuranosyl
      cytosine (ara-C), which is a well-known deoxycytidine analog and inhibits DNA
      polymerase alpha, did not inhibit RNR in LX-1 lung carcinoma at doses
      demonstrating antitumor activity. These results indicate that MDL101,731
      exhibited antitumor activity through inhibition of RNR activity in tumor cells in
      vivo and the mechanism of antitumor action of MDL 101,731 might be different from
      those of DMDC and ara-C, at least in part.

PMID- 9773811
TI  - Neurotoxic effect of cisplatin and the cisplatin-procaine complex DPR studied in
      organotypic cultures of chick embryonic dorsal root ganglia.
AB  - Neurotoxic effects of cisplatin and the cisplatin-procaine complex cis
      diaminechloro-[2-(diethylamino)ethyl 4-aminobenzoate, N4]-chlorideplatinum(II)
      monohydrochloride monohydrate (DPR) were compared in organotypic cultures of
      chick embryonic dorsal root ganglia maintained in a semi-solid (soft agar)
      culture medium. The changes of two characteristics of the neurite outgrowth, the
      mean radial length of neuritic processes growing out from the ganglia and the
      area of neurite outgrowth around the ganglion, were used as parameters to
      evaluate the toxic effect of both compounds. The drugs were administered to the
      cultures at concentrations ranging from 13 to 120 microM. The half-maximum
      inhibition concentration (IC50) was determined from the concentration-response
      curves for both the mean radial length of neurites and the area of neurite
      outgrowth. An analysis of these parameters revealed that DPR was significantly
      less neurotoxic than cisplatin. In fact, considering the mean radial length of
      neurite processes, the IC50s of cisplatin were 56, 65 and 66 microM after 24, 48
      and 72 h of exposure, respectively. By contrast, for DPR the IC50s were 116
      microM after 24 h, and greater than 120 microM after 48 and 72 h of exposure.
      When we considered the area index (i.e. the area of neurite outgrowth normalized
      for the area of the ganglia), the IC50s for cisplatin were 41, 52 and 55 microM
      after 24, 48 and 72 h of exposure, respectively, whereas for DPR the IC50s were
      59 microM after 24 h, and greater than 120 microM after 48 and 72 h of exposure.
      Our results support previous findings of lower toxicity of DPR to non-neoplastic
      tissues, as compared to cisplatin.

PMID- 9773812
TI  - A surface plasmon resonance study of albumin adsorption to PEO-PPO-PEO triblock
      copolymers.
AB  - Pluronic surfactants, PEO-PPO-PEO triblock copolymers, have been investigated
      widely due to their protein-resistant properties in applications as coatings for
      implants and in controlled drug release systems. We have studied a wide range of
      these copolymers, varying in both PEO and PPO block size, by adsorbing them to a
      polystyrene surface and investigating their subsequent resistance to human serum
      albumin adsorption. This investigation has been carried out in real time, using
      surface plasmon resonance, with the surfaces subsequently visualized by atomic
      force microscopy. This approach has allowed determination of the effect of the
      lengths of the PEO and PPO polymer chains on protein resistivity. For low
      molecular-weight Pluronics a significant, yet not complete, reduction in albumin
      adsorption has been observed whereas higher molecular weight Pluronics appear to
      completely inhibit adsorption within the time frame of this experiment. An
      increase in the PPO block size of the copolymer also appears to increase its
      protein resistance. This work further confirms that the binding strength of the
      anchoring block to the hydrophobic surface, rather than the length of the
      protruding hydrophilic PEO chains, determines a copolymer's protein resistance
      capability.

PMID- 9773813
TI  - Cartilage tissue engineering with novel nonwoven structured biomaterial based on
      hyaluronic acid benzyl ester.
AB  - The aim of this study was to investigate the possibility of using the benzyl
      ester of hyaluronic acid (HYAFF 11), a recently developed semisynthetic
      resorbable material, as a scaffold for the culture of human nasoseptal
      chondrocytes in tissue-engineering procedures of cartilage reconstruction.
      Different techniques such as immunohistochemistry, scanning electron microscopy,
      and confocal laser scanning microscopy were used to study the behavior,
      morphology, and phenotype expression of the chondrocytes, which were initially
      expanded and then seeded on the material. The nonwoven cell carrier allowed good
      viability and adhesivity of the cells without any surface treatment with
      additional substances. Furthermore, the cultured cells expressed cartilage
      specific collagen type II, indicating that they were able to redifferentiate
      within the scaffold of HYAFF 11 and were able to retain a chondrocyte phenotype
      even after a long period of in vitro conditions. Nevertheless, the expression of
      collagen type I, which was produced by dedifferentiated or incompletely
      redifferentiated chondrocytes, was noticeable. Additional data were obtained by
      subcutaneous implantation of samples seeded with human cells in the in vivo model
      of the athymic nude mouse. The results after 1 month revealed the development of
      tissue similar to hyaline cartilage. This study is promising for the use of this
      scaffold for tissue engineering of cartilage replacements.

PMID- 9773814
TI  - Poly-L-lysine amplification of protamine immobilization and heparin adsorption.
AB  - We previously reported the development of a cellulose fiber based blood filter
      device containing immobilized protamine (termed protamine filter) that could be
      used to control both heparin- and protamine-induced complications during
      extracorporeal therapy. To achieve enhanced heparin adsorption on the fibers, we
      examined the possibility of utilizing the poly-L-lysine based amplification
      method to augment protamine loading on the fiber, as well as to create multiple
      layers of immobilized protamine for heparin interaction. Results show that such a
      method yielded about a threefold increase in protamine loading and, consequently,
      about a fourfold enhancement in heparin adsorption when compared with the control
      without poly-L-lysine amplification. This technological improvement may
      facilitate development of a new generation of protamine filters with capacity and
      efficacy suitable for various clinical applications in extracorporeal heparin
      removal.

PMID- 9773815
TI  - Effects of amide and amine plasma-treated ePTFE vascular grafts on endothelial
      cell lining in an artificial circulatory system.
AB  - We sought to examine whether surface modification of expanded
      polytetrafluoroethylene (ePTFE) vascular grafts might extend graft patency
      without modifying the graft structure. Amide and amine plasma (butylamine) were
      applied to graft surfaces using radio frequency glow discharge. Surface analyses
      by Fourier transform infrared spectroscopy-attenuated total reflectance, X-ray
      photoelectron spectroscopy, and dynamic contact angle measurements revealed the
      presence of nitrogen-containing functional groups on the plasma modified graft
      surfaces, along with an increased surface hydrophilicity. Bovine aortic
      endothelial cells were seeded on amide and amine plasma coated ePTFE vascular
      grafts and placed inside an artificial circulatory system under well-defined flow
      conditions. The seeded endothelial cells were exposed to either constant or
      pulsatile flow condition for 5 days. Their corresponding maximum wall shear
      stresses were 1 dyn/cm2 under constant flow and 65, 108, and 259 dyn/cm2 under
      various pulsatile flows. Plasma modified ePTFE vascular grafts enhanced the
      endothelial cell lining under constant and pulsatile flow conditions.
      Fluorescence nuclear staining, scanning electron microscopy, and histological
      staining indicated the formation of an endothelial cell monolayer on the plasma
      coated graft surfaces.

PMID- 9773816
TI  - Decreased consumption of Ca and P during in vitro biomineralization and
      biologically induced deposition of Ni and Cr in presence of stainless steel
      corrosion products.
AB  - The purpose of this study was to investigate the effects of 316L stainless steel
      (SS) corrosion products on the in vitro biomineralization process, because tissue
      necrosis, bone loss, impaired bone mineralization, and loosening of orthopedic
      implants are associated with ions and debris resulting from biodegradation. Rat
      bone marrow cells were cultured in experimental conditions that favored the
      proliferation and differentiation of osteoblastic cells and were exposed to SS
      corrosion products obtained by electrochemical means for periods ranging from 1
      to 21 days. Quantification of total and ionized Ca and P, as well as Fe, Cr, and
      Ni, ions in the culture media of control and metal added cultures during the
      incubation period was performed to study the influence of corrosion products on
      the Ca and P consumption that occurs during the mineralization process. Control
      cultures and metal effects on cultures were evaluated concerning DNA content,
      enzymatic reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT), and alkaline phosphatase (ALP) activity. Histochemical detection
      of ALP, Ca, and phosphate deposition, and examination of the cultures by scanning
      and transmission electron microscopy (SEM and TEM) were also performed. The
      presence of SS corrosion products resulted in impairment of the normal behavior
      of rat bone marrow cultures. Levels of Cr and Ni in the medium of cultures
      exposed to 316L SS corrosion products decreased throughout the incubation period,
      suggesting a regular deposition of these species; these results were supported by
      TEM observation of the cultures. Cultures exposed to the corrosion products
      presented lower DNA content, MTT reduction, and ALP activity and failed to form
      mineralized areas. These cultures showed negative staining on histochemical
      reactions for the identification of calcium and phosphate deposition and SEM and
      TEM examination did not show mineral globular structures or mineralization foci,
      respectively, which is characteristic of cultures grown in control conditions.
      These results suggest that metal ions associated with 316L SS are toxic to
      osteogenic cells, affecting their proliferation and differentiation.

PMID- 9773817
TI  - Cartilage formation by fetal rat chondrocytes cultured in alginate beads: a
      proposed model for investigating tissue-biomaterial interactions.
AB  - Chondrocytes from 21-day-old rat fetal nasal cartilage were cultured in alginate
      beads for up to 20 days. It was found that chondrocytes retained their spherical
      shape and typical chondrocytic appearance. During the culture time, chondrocytes
      underwent differentiation, as demonstrated by the alkaline phosphatase-specific
      activity and rate of proteoglycan synthesis. Morphological data confirmed
      chondrocyte differentiation with the appearance of hypertrophic chondrocytes
      scattered in the alginate gel and a dense extracellular matrix containing
      filamentous structures and matrix vesicles. In addition, Northern blot analysis
      performed on day 8 of culture showed that chondrocytes cultured in alginate beads
      expressed type II collagen mRNA. The alginate bead method also appeared to be
      suitable for testing biomaterials, and the ready dissolution of the alginate
      beads by chelating agents provided a simple means for the rapid recovery of
      encapsulated chondrocytes. Powdered glass-ceramic particles entrapped in the
      alginate gel were colonized by chondrocytes, which then proliferated and formed a
      tissue similar to a true calcified cartilaginous structure. These results
      indicate that the alginate system represents a relevant model for studies of
      chondrogenesis and endochondral ossification. Furthermore, the encapsulation
      method could prove useful for studies of tissue-biomaterial interactions in an in
      vitro environment which more closely mirrors the cartilage matrix than other
      culture methods.

PMID- 9773818
TI  - Bioactive bone cement: comparison of apatite and wollastonite containing glass
      ceramic, hydroxyapatite, and beta-tricalcium phosphate fillers on bone-bonding
      strength.
AB  - A study was conducted to compare the bone-bonding strengths of three types of
      bioactive bone cement, consisting of either apatite- and wollastonite-containing
      glass-ceramic (AW-GC) powder, hydroxyapatite (HA) powder, or beta-tricalcium
      phosphate (beta-TCP) powder as an inorganic filler and bisphenol-a-glycidyl
      methacrylate (Bis-GMA) based resin as an organic matrix. Seventy percent (w/w)
      filler was added to the cement. Rectangular plates (10 x 15 x 2 mm) of each
      cement were made and abraded with #2000 alumina powder. After soaking in
      simulated body fluid for 2 days, the AW cement (AWC) and HA cement (HAC) formed
      bonelike apatite over their entire surfaces, but the TCP cement (TCPC) did not.
      Plates of each type of cement were implanted into the tibial metaphyses of male
      Japanese white rabbits, and the failure loads were measured by a detaching test
      at 10 and 25 weeks after implantation. The failure loads of AWC, HAC, and TCPC
      were 3.95, 2.04, and 2.03 kgf at 10 weeks and 4.36, 3.45, and 3.10 kgf at 25
      weeks, respectively. The failure loads of the AWC were significantly higher than
      those of the HAC and TCPC at 10 and 25 weeks. Histological examination by contact
      microradiogram and Giemsa surface staining of the bone-cement interface revealed
      that all the bioactive bone cements were in direct contact with bone. However,
      scanning electron microscopy and energy-dispersive X-ray microanalysis showed
      that only AWC had contacted to the bone via a Ca-P rich layer formed at the
      interface between the AW-GC powder and the bone, which might explain its high
      bone-bonding strength. Neither the HAC nor the TCPC contacted the bone through
      such a layer between each powder and the bone, although the HAC and TCPC directly
      contacted with bone. Our results indicate that all three types of abraded and
      prefabricated cement have bonding strength to bone, but AWC has superior bone
      bonding strength compared to HAC and TCPC.

PMID- 9773819
TI  - Comparison of growth and metabolism of avian osteoblasts on polished disks versus
      thin films of titanium alloy.
AB  - The purpose of this study was to evaluate the efficacy of using high vacuum,
      thermal evaporation to deposit thin films of Ti-6Al-4V onto plates for subsequent
      cell culture investigations. Osteoblastic response to thin-film coated plates was
      compared to that of cells grown on Ti alloy disk inserts and uncoated culture
      plates. The Ti alloy disks were polished, cleaned, and passivated following a
      commercial protocol for orthopedic implants. Mean surface roughness was 262 nm
      for the Ti alloy disks and 4.756 nm for the coated culture plates. Osteoblasts
      isolated from 16-day chick embryo calvariae were cultured on polystyrene, thin
      films, and disks. At confluence, the cells were cultured an additional 48 h and
      were evaluated for cell number (DNA content), rate of glycolysis (lactate
      production), alkaline phosphatase activity (ALPase), and collagenous (3H-proline
      hydroxylation) and noncollagenous protein synthesis. Cell morphology was similar
      for the controls, disks, and thin-film groups. DNA, lactate, cell layer ALPase,
      3H-hydroxyproline, and noncollagenous protein were not different (p > 0.05) among
      the control, thin-film, and disk groups. Medium ALPase was lower (p < 0.05) in
      the thin-film group compared to the control group. Although aluminum and vanadium
      percentages varied from nominal in the thin-film groups (11Al-2V as opposed to
      6Al-4V), avian osteoblasts responded similarly to the Ti alloy thin films, disks,
      and uncoated culture plates for the smooth surfaces tested. The thin-film cell
      culture system used for elemental material studies appears to offer a promising
      method for the investigation of cellular response to alloyed biomaterials as
      well. Proper adjustments in alloy percentages before deposition, however, need to
      be made if thermal evaporation is utilized.

PMID- 9773820
TI  - Surface topography can interfere with epithelial tissue migration.
AB  - Corneal epithelial tissue migration over the surface of a synthetic polymer can
      be inhibited by pores in the substrate. The effects of this substrate topography
      upon epithelial tissue migration were studied in vitro. Membranes of different
      porosities and structures were used to provide two series of surfaces having a
      graded increase in discontinuities: cellulose nitrate/acetate membranes with a
      tortuous network of pores, and track-etched polycarbonate membranes with columnar
      pores. Corneal epithelial tissue outgrowth was inhibited by increased pore size,
      and for both series of membranes, outgrowth was completely halted on membranes
      with mean diameter of the pores 0.9 microm at the pore densities measured. On the
      track-etched membranes with pores of <0.9 microm diameter, tissue outgrowth could
      be partially "rescued" by coating with fibronectin or collagen, but above this
      size, the inhibition predominated. The effect of porosity of the track-etched
      membranes upon the migration of dissociated epithelial cells was also examined.
      Although migration of these cells was reduced on membranes having pore sizes
      larger than 0.9 microm, it was not completely inhibited even on membranes of 2.3
      microm pore diameter. Therefore, tissue movement of adult stratified epithelium
      may be inhibited by specific surface topographies, and in this assay system,
      epithelial tissue outgrowth was more affected than was the migration of
      dissociated epithelial cells.

PMID- 9773821
TI  - Bone bonding in bioactive glass ceramics combined with bone matrix gelatin.
AB  - To determine how to encourage inductive osteogenesis on bioactive ceramics and
      accelerate the bonding of implants to the surrounding bone, we studied the role
      of autolyzed antigen-extracted allogeneic bone gelatin (AAAG) in bone bonding to
      bioactive ceramic implants in rabbit tibiae. Smooth-surfaced plates (15 x 10 x 2
      mm) of apatite and wollastonite containing glass-ceramic were implanted into the
      proximal metaphyses of tibiae, with AAAG packed into the medullary cavity in one
      limb but not in the contralateral limb, which served as a paired control. After
      2, 4, 8, 16, and 25 weeks, bone bonding and bone formation at the bone/implant
      interfaces were evaluated by a detaching test and undecalcified histological
      examination. The tensile failure load increased from 2 to 25 weeks for both
      groups. The failure load of the AAAG-treated group was significantly greater than
      that of the control group at every stage. Histologically, the AAAG-treated
      specimens showed active new bone formation in the medullary cavity and extensive
      bonding between the implant and bone at early periods. The percentage of bony
      covering in the AAAG-treated group was significantly higher than that of the
      controls at all intervals except at 25 weeks. The results of this study suggest
      that the addition of osteoinductive AAAG to a bioactive implant may significantly
      accelerate bone apposition to the implant and improve the bonding process at the
      interface, which would help to establish an earlier and stronger bonding between
      the implants and the surrounding bone.

PMID- 9773822
TI  - A complete characterization of Ca5(PO4)3OH sputter-deposited films by ion beam
      analysis: RBS and ERD.
AB  - RF magnetron sputter deposition was used to deposit thin calcium phosphate
      (hydroxyapatite) layers on titanium alloy substrate material. We determined the
      precise amount of calcium, phosphorus, oxygen, and hydrogen in these films by
      combining two ion-beam analysis techniques: Rutherford backscattering
      spectrometry (RBS) and elastic recoil detection (ERD). Variables were power
      level, partial oxygen pressure, or additional water vapor. Also examined was the
      influence of additional bias power to the substrates during deposition and the
      effect of annealing on the final composition of the deposited layers.
      Measurements showed that the Ca/P ratio decreased with increasing oxygen pressure
      or decreasing sputtering power. In addition, the Ca/P ratio increased when a bias
      was applied to the substrates. The O/P ratio of the films decreased with
      additional oxygen pressure but increased when additional water vapor was applied
      during deposition. All as-deposited films showed a higher hydrogen content than
      stoichiometric HA. The hydrogen content in the films deposited with water vapor
      was more than 7 times higher than in the films deposited under pure argon
      conditions. After annealing, the hydrogen content decreased to about 3.5 at %
      whereas in stoichiometric HA the hydrogen content amounts to 4.5 at %. After
      annealing, the oxygen concentration in the film also decreased. We assume that
      hydrogen disappears out of the film as H2O during annealing. For the targets used
      in these experiments, sputter deposition at 400 W, with additional water vapor
      and annealing at 500 degrees C, produced films with a stoichiometry closest to
      that of hydroxyapatite.

PMID- 9773823
TI  - The effect on immunocytes of anodic oxide titanium after hydrothermal treatment.
AB  - All dental root implants come in contact with the oral epithelium, and many
      complex factors are found to arise in this region. In order to perform a
      successful dental root implantation, it is necessary to clarify the interaction
      of the dental root implant material with the host defense mechanisms involved in
      the specific and nonspecific immune responses to many antigens in oral bacteria
      and their components. Recently, focusing on developing the dental root implant,
      the Nikon Corporation improved the surface characteristics of pure titanium even
      further by developing a hydroxyapatite (HA) layer formed on an anodic titanium
      oxide film containing Ca and P via hydrothermal treatment (SA treatment).
      However, since little is known about the effect of SA-treated pure titanium
      (HA/Ti) on the defense mechanisms of the oral membrane epithelium, we
      investigated (1) the in vitro proliferation of murine splenic B lymphocytes on
      the surface of HA/Ti in the presence of three lipopolysaccharide (LPS)
      concentrations and (2) interleukin-1alpha (IL-1alpha) production by the reaction
      of human peripheral blood mononuclear cells (PBM cells) on the surface of HA/Ti
      under the same concentrations. After culture, murine splenic lymphocytes were
      measured by uptake of 3H-thymidine, and cytokine release (IL-1alpha) from PBM
      cells was measured by ELISA. Results showed that HA/Ti had hardly any effect on
      the LPS-induced proliferation of B lymphocytes and IL-1alpha production. In vitro
      investigations of the effects of HA/Ti on the LPS-induced proliferation of murine
      splenic B lymphocytes and IL-1alpha from PBM cells might be a useful way of
      elucidating the defense mechanism between implants and the oral epithelium.

PMID- 9773824
TI  - Osteoclastic resorption of bone-like apatite formed on a plastic disk as an in
      vitro assay system.
AB  - We have investigated the applicability of a simple and inexpensive osteoclastic
      assay system using bone-like apatite-coated polyethyleneterephthalate (PET)
      disks. A 1 microm thick apatite layer, uniform and homogeneous bone-mineral-like
      with no organic components, was made on PET disks using a biomimetic process. As
      substrates for an osteoclastic assay, these coated disks were compared with
      dentine as well as with bone-like or heat-treated apatite of various thicknesses
      on apatite- and wollastonite-containing glass ceramic (A-W GC) disks. The
      unfractionated bone cells, including osteoclasts, of a neonatal rabbit were
      seeded onto these substrates. By scanning electron microscopic examination, the
      resorption lacunae of the thick bone-like apatite clearly showed track-like
      shapes at various depths, similar to those of dentine although the border between
      the A-W GC and the apatite was unclear. In contrast, those of heat-treated
      apatite showed small and shallow shapes with irregular margins, quite different
      from those of dentine. By reducing the thickness of bone-like apatite to 1 microm
      as well as using PET as its substrate, the margins of the resorption lacunae
      became quite clear, and with the use of phase-contrast microscopy during culture,
      osteoclasts and resorption pits could be precisely observed. The resorbed area,
      easily measured with the aid of bright-field microscopy and an image analyzer,
      was found to have increased in a time-dependent manner and at the end of 4 days
      of culture was not statistically different from that of dentine.

PMID- 9773825
TI  - Chemically modified dextrans modulate expression of collagen phenotype by
      cultured smooth muscle cells in relation to the degree of carboxymethyl,
      benzylamide, and sulfation substitutions.
AB  - We developed regenerating agents (RGTAs) corresponding to polysaccharides derived
      from dextran and containing defined amounts of carboxymethyl (CM), carboxymethyl
      sulfate (CMS), carboxymethyl benzylamide (CMB), or carboxymethyl benzylamide
      sulfate (CMBS) groups with varying degrees of substitution. These compounds
      mimicked some effects of heparin on smooth muscle cell (SMC) proliferation and
      promoted in vivo tissue remodeling. We demonstrated that only RGTAs containing
      both CM and sulfate groups decreased SMC proliferation, in correlation with
      increased sulfation level. This effect was amplified by the presence of
      benzylamide. Independent of this activity on cell proliferation (i.e., with
      postconfluent cells), RGTAs modulated collagen biosynthesis by SMCs. On the one
      hand, CMBS more than CMS RGTAs induced a decrease of collagen III synthesis at
      the level of mRNA steady state and protein production. On the other hand, CMS to
      a greater extent than CMBS RGTAs increased both collagen V mRNA and protein
      production. In addition, only benzylamide-containing RGTAs increased accumulation
      of collagen I and III in the cell layer. In conclusion, RGTA bioactivities
      required the presence of CM functions, increased with the sulfation level, and
      varied with benzylamide substitution. RGTAs that modulate cell proliferation and
      collagen biosynthesis by differential mechanisms may represent potential
      antifibrotic agents.

PMID- 9773826
TI  - Influence of sol and surface properties on in vitro bioactivity of sol-gel
      derived TiO2 and TiO2-SiO2 films deposited by dip-coating method.
AB  - Different sol-gel-derived titania and titania-silica films were prepared and
      their properties related to in vitro bioactivity. The films were prepared by
      depositing the sols on the substrate surface using a dip-coating method. The sols
      were monitored carefully as a function of time, using rheological techniques and
      dynamic light scattering. The topography of the films was characterized using
      atomic force microscopy, and thicknesses and refractive indexes of the films were
      evaluated by fitting transmittance spectra measured in a wave length region of
      370-1100 nm with a spectrophotometer. The in vitro bioactivity tests were
      performed in simulated body fluid. Surface topography was found to be of great
      importance with respect to the bioactivity of the studied films.

PMID- 9773827
TI  - Biodegradation and biocompatibility of a guided tissue regeneration barrier
      membrane formed from a liquid polymer material.
AB  - Biodegradable barrier films were made by coagulating a solution of poly(DL
      lactide) in N-methyl-2-pyrrolidone on porous polyethylene pads wetted with saline
      solution. The semisolid films were cut into 10 x 10 mm barriers and implanted
      subcutaneously in rabbits. At monthly intervals, the polymer implant sites were
      compared histologically to those implanted with USP negative control plastic. The
      polymer films were retrieved from the surrounding tissue, dried, weighed, and the
      changes in molecular weight determined using gel permeation chromatography. The
      molecular weight of the polymer decreased at a relatively constant rate over 5
      months; however, no significant mass loss occurred until 5 months
      postimplantation. Also, no distinct histological differences were noted between
      the polymer barrier and the control plastic sites until 6 months when histiocytes
      and multinucleated giant cells showed a modest increase around fragmented polymer
      films. Similar barrier films also were fitted over naturally occurring buccal
      dehiscence defects in beagle dogs and the tissue sites compared histologically at
      6 months to sham-operated control sites. New bone and dense connective tissues
      closely approximated segments of the remaining polymer and demonstrated the
      biocompatibility of the biodegradable films. Histomorphometric analyses of
      treated sites compared to sham controls showed that the polymer barrier is
      effective in promoting bone and cementum regeneration in periodontal defects in
      dogs.

PMID- 9773828
TI  - In vitro and in vivo degradation of poly(propylene fumarate-co-ethylene glycol)
      hydrogels.
AB  - The degradation of poly(propylene fumarate-co-ethylene glycol) hydrogels was
      examined in vitro in phosphate-buffered saline at pH 7.4 and in vivo in a
      subcutaneous rat model. These hydrogels have potential application as
      biodegradable, injectable cardiovascular stents, and, as such, their mass loss,
      dimensional changes, mechanical properties, morphology, and biocompatibility over
      a 12-week time course were evaluated. Three formulations were fabricated: one
      base formulation consisting of 25% (w/w) PEG, molecular weight 4,600; one high
      weight percent PEG formulation with 50% (w/w) PEG; and one high molecular weight
      PEG formulation, molecular weight 10,500. All three formulations showed
      significant weight loss (between 40 and 60%) on the first day due to leaching of
      the uncrosslinked fraction. Further weight loss was observed only for the low
      weight percent PEG copolymers in the in vivo case, and a slight increase in
      volume was observed due to degradative swelling. The mechanical properties of the
      P(PF-co-EG) hydrogels decreased significantly in the first 3 weeks, showing the
      biphasic pattern typical of bulk degradation. In vitro, the hydrogels showed at
      least a 20% retention of their initial ultimate tensile stress after 3 weeks. The
      dynamic mechanical properties showed similar retention, with the in vivo
      mechanical properties differing from the in vitro properties only after 6 weeks
      of degradation. Differences in PEG molecular weight appeared to have little
      effect, but increasing the weight percent PEG decreased the rate of degradation
      both in vitro and in vivo. The morphology of the copolymer films, based on
      scanning electron microscopy observation, was not significantly different either
      among the three formulations or over the time course of the study, suggesting
      there were no macroscopic structural changes during this time period. The P(PF-co
      EG) hydrogels demonstrated good initial biocompatibility, showing responses
      characteristic of biomaterial implants.

PMID- 9773829
TI  - The reduction half cell in biomaterials corrosion: oxygen diffusion profiles near
      and cell response to polarized titanium surfaces.
AB  - Mechanically assisted corrosion processes can greatly increase the oxidation
      currents generated in passivating alloy systems like Co-Cr and titanium due to
      oxide film disruption. When oxide films are abraded, repassivation and ionic
      dissolution both occur at rates that are orders of magnitude higher than
      undisrupted surfaces. The excess electrons generated by these anodic processes
      must be consumed in corresponding reduction reactions that include the reduction
      of oxygen. If large enough, these reduction reactions may locally deplete the
      concentration of solution-dissolved oxygen and, in turn, affect cell behavior in
      the vicinity of the implant surface. To date, this hypothesis has not been
      tested. In the present study, a scanning electrochemical microscope was used to
      measure oxygen concentration profiles in vitro near a planar titanium electrode
      polarized to different voltages representative of those attainable by titanium
      undergoing mechanically assisted corrosion. The potentials investigated ranged
      from 0 mV to -1000 mV (AgCl). The oxygen concentration as a function of distance
      from the titanium surface was measured using a platinum-iridium microelectrode
      and an amperometric technique. Also, preliminary experiments were performed to
      assess the response of rat calvarial osteoblast-rich cells cultured for 2 h on
      titanium samples polarized to two different potentials (0 mV and -1000 mV versus
      AgCl). The results of this study indicate that oxygen concentrations near
      titanium surfaces are affected by sample potentials out to probe-sample distances
      as great as 500 microm. Within 2 microm of the surface, oxygen concentrations
      decreased by 15 to 25% for sample potentials between -100 and -500 mV. At
      potentials more negative than -600 mV, the oxygen concentration dropped rapidly
      to near zero by -900 mV. The cell experiments showed a statistically significant
      difference in the amount of cell spreading, as measured by projected cell area,
      between the two groups (p < 0.03), with the cells cultured at -1000 mV undergoing
      much less spreading. This implies that -1000 mV inhibits normal cell behavior at
      the titanium surface and that this is most likely due, at least in part, to a
      diminished oxygen supply.

PMID- 9773831
TI  - Adverse reactions due to Aquavene.

PMID- 9773830
TI  - Regulation of smooth muscle cell proliferation using paclitaxel-loaded
      poly(ethylene oxide)-poly(lactide/glycolide) nanospheres.
AB  - Available data suggest that drugs should be delivered to a vascular lesion at a
      high concentration over an extended period of time to control vascular smooth
      muscle cell (VSMC) proliferation. This study was undertaken to formulate a
      paclitaxel, an antimicrotubule agent, into a biodegradable poly (ethylene oxide)
      poly(lactide/glycolide) (PEO-PLGA) nanosphere as a sustained drug delivery system
      and to study its effects on VSMC in culture. The paclitaxel-loaded nanospheres
      (PT/NS), prepared by an emulsion-solvent evaporation method, had an average
      diameter of approximately 150 nm and showed a sustained release profile over 4
      weeks. The PT/NS exhibited antiproliferative effects comparable to those observed
      with free paclitaxel. The cellular internalization of nanospheres was visualized
      using confocal fluorescence microscopy, and from a flow cytometry study the
      progressive cellular uptake profile, uptake inhibition at low temperature, and
      saturation uptake kinetics (concentration dependency) were observed. These
      suggest that (adsorptive) pinocytosis is a major uptake mechanism of the
      nanospheres. The sustained drug release profile and cellular internalization
      results suggest that nanospheres loaded with paclitaxel may potentially be used
      as an endocytizable, local sustained drug delivery system for the prevention of
      restenosis.

PMID- 9773832
TI  - Defective natural killer cell function in patients with hemophagocytic
      lymphohistiocytosis and in first degree relatives.
AB  - Hemophagocytic lymphohistiocytosis (HLH), also referred to as familial
      erythrophagocytic lymphohistiocytosis, is a rare disorder of infancy associated
      with proliferation of activated histiocytes and T cells, anemia,
      thrombocytopenia, and fevers. This disorder appears to be due to the uncontrolled
      activation of T cells producing IL-2, tumor necrosis factor-alpha, and interferon
      gamma. Untreated, the disorder is universally fatal. Various deficits in immune
      function have been described during acute disease activity including impaired T
      cell function, impaired monocyte-mediated antibody-dependent cytotoxicity,
      impaired natural killer cell function, and impaired IL-1 production. We examined
      natural killer cell function in familial HLH patients to determine whether this
      finding was consistently associated with the disease. We also examined natural
      killer cell function in asymptomatic parents and siblings of patients. Impaired
      natural killer cell function was identified in all patients and in some family
      members, including obligate carrier parents. This implies that one potential
      genetic defect in HLH may result in depressed natural killer function, but that
      this may not be sufficient to reliably predict eventual progression to disease.

PMID- 9773834
TI  - Atopic sensitization during the first year of life in relation to long chain
      polyunsaturated fatty acid levels in human milk.
AB  - The levels of the long chain polyunsaturated n-6 and n-3 fatty acids (PUFA) were
      studied in colostrum and mature milk of 29 atopic and 29 nonatopic mothers and
      related to sensitization in their babies during the first 12 mo of life. The
      levels of alpha-linolenic acid (LNA) were lower (0.96 versus 1.23 weight
      percentage, p < 0.01) and the levels of dihomo-gamma-linoleic acid were higher
      (0.36 versus 0.31 weight percentage, p < 0.05) in mature milk from mothers of
      atopic babies (n = 24) compared with mothers of nonatopic babies (n = 34). The
      total n-3 levels and the ratio of n-6 PUFA/n-3 PUFA were similar in colostrum of
      all mothers and then decreased significantly in mature milk (p < 0.001),
      particularly in milk given to atopic babies. The levels of the n-6 fatty acids
      arachidonic acid, C22:4, and C22:5 n-6 correlated in milk samples from nonatopic
      mothers (r = 0.61-0.97, p < 0.05 to p < 0.001) but were largely absent in
      colostrum and mature milk from atopic mothers. In contrast, LNA and
      eicosapentaenoic levels correlated in colostrum from the atopic mothers (r = 0.61
      0.88) regardless of atopic sensitization in the infants, whereas LNA correlated
      to C20:4 n-3 in colostrum from nonatopic mothers of nonatopic infants.
      Furthermore, the levels of the n-3 fatty acid C20:4 n-3 correlated significantly
      to all n-6 fatty acids, except linoleic acid (r = 0.64-0.79, all p < 0.01) in
      mature milk from nonatopic mothers of nonsensitized children. Low levels of LNA
      and total n-3 long chain polyunsaturated fatty acids, in mature milk from the
      mothers, appear to be associated with atopic sensitization early in life, as well
      as disturbed relationships between the n-3 fatty acid 20:4 and the n-6 fatty
      acids particularly in mature milk. On the other hand, disturbed relationships
      within the individual fatty acids in the n-6 series in human milk reflected the
      atopic status in the mothers. The variations in the lipid composition of human
      milk could in part explain some of the controversies regarding the protective
      effects of breast-feeding against allergy.

PMID- 9773833
TI  - Plasma levels and gene expression of granulocyte colony-stimulating factor, tumor
      necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-8, and soluble
      intercellular adhesion molecule-1 in neonatal early onset sepsis.
AB  - Bacterial sepsis is still a leading cause of neonatal morbidity and mortality.
      Early onset sepsis in particular, presents with a different clinical course and
      involves other pathogens than sepsis later in life. In this study, plasma
      concentrations and mRNA expression of granulocyte colony-stimulating factor (G
      CSF), tumor necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6, IL-8, and soluble
      intercellular adhesion molecule-1 (sICAM-1) of neonates with early onset sepsis
      were evaluated in cord blood and during the first days of life. Irrespective of
      prematurity, plasma levels of G-CSF, TNF-alpha, IL-1beta, IL-6, and IL-8, but not
      sICAM-1, were excessively elevated in septic neonates when compared with both
      healthy infants and infants with clinically suspected but not confirmed sepsis.
      Compared with the corresponding maternal levels, neonatal cytokine cord plasma
      levels were likewise highly elevated, indicating the endogenous cytokine
      production by the neonate. With the exception of TNF-alpha, mRNA expression in
      blood cells from septic infants was, however, not more frequently detectable than
      in those from nonseptic patients. Cytokine levels decreased significantly within
      the first days of life, whereas levels of sICAM-1 and C-reactive protein
      increased during the same time period. In summary, in contrast to C-reactive
      protein and sICAM-1, cord blood plasma levels, but not the presence of mRNA, of G
      CSF, TNF-alpha, IL-1beta, IL-6, and IL-8 can predict neonatal early onset sepsis
      with a high sensitivity and specificity. Cell types other than blood cells are
      likely to contribute considerably to the high cytokine production in septic
      newborns.

PMID- 9773835
TI  - Clinical food hypersensitivity: the relevance of duodenal immunoglobulin E
      positive cells.
AB  - Owing to poor reliability of laboratory tests, diagnosis of food allergy is based
      on clinical response to double-blind placebo-controlled food challenge. The aim
      of the present study was to assess the value of duodenal IgE-positive cells in
      the diagnosis of food allergy. Thirty-one children with a history of possible
      food allergy underwent duodenal biopsies, skin prick tests, and measurement of
      serum IgE antibodies, and were put on an elimination diet followed by food
      challenge. Open food challenges were performed in patients under 12 mo of age,
      and double-blind placebo-controlled challenges were for suspected foods. On the
      basis of clinical food hypersensitivity, patients were divided into two groups.
      Group 1 consisted of 13 children with food allergy. Thirteen of 20 positive
      provocations elicited reactions within 12 h from the end of the challenge, seven
      later. Group 2 was the control group and included 18 patients with negative food
      challenges. The number of IgE-positive cells in biopsy specimens was
      significantly more elevated in group 1 with respect to group 2 (153.24 +/- 83.13
      versus 18.4 +/- 18.9; p < 0.01). Total serum IgE levels were elevated compared
      with that of the control group (p < 0.01) and correlated with the number of IgE
      positive cells (p < 0.001, r = 0.62). Enhanced IgE-containing cells were found in
      all delayed reactors, but about one-third had negative skin prick tests or
      specific serum IgE antibodies to the offending foods. Our results showed that
      systemic reactions to foods are associated with an IgE-mediated response in the
      duodenal mucosa. Larger studies would be required to assess the predictive value
      of an increased number of IgE-positive cells in the diagnosis of allergy to food,
      especially in children with delayed reactions.

PMID- 9773836
TI  - Lower incidence of necrotizing enterocolitis in infants fed a preterm formula
      with egg phospholipids.
AB  - Necrotizing enterocolitis (NEC) causes approximately 4000 deaths/y and
      significant morbidity among U.S.-born preterm infants alone. Various combinations
      of inadequate tissue oxygenation, bacterial overgrowth, and enteral feeding with
      immaturity may cause the initial damage to intestinal mucosa that culminates in
      necrosis. Presently, there is not a way to predict the onset of the disease or to
      prevent its occurrence. As part of risk-benefit assessment, we compared disease
      in hospitalized preterm infants fed a commercial (control) preterm formula or an
      experimental formula with egg phospholipids for a randomized, double-masked,
      clinical study of diet and infant neurodevelopment. Infants fed the experimental
      formula developed significantly less stage II and III NEC compared with infants
      fed the control formula (2.9 versus 17.6%, p < 0.05), but had similar rates of
      bronchopulmonary dysplasia (23.4 versus 23.5%), septicemia (26 versus 31%), and
      retinopathy of prematurity (38 versus 40%). Compared with the control formula,
      the experimental formula provided 7-fold more esterified choline, arachidonic
      acid (AA, 0.4% of total fatty acids), and docosahexaenoic acid (0.13%).
      Phospholipids are constituents of mucosal membranes and intestinal surfactant,
      and their components, AA and choline, are substrates for intestinal vasodilatory
      and cytoprotective eicosanoids (AA) and the vasodilatory neurotransmitter,
      acetylcholine (choline), respectively. One or more of these components of egg
      phospholipids may have enhanced one or more immature intestinal functions to
      lower the incidence of NEC in this study. Regardless of the potential mechanism,
      a larger randomized trial designed to test the effect of this egg phospholipid
      containing formula on NEC seems warranted.

PMID- 9773837
TI  - Milk fat globule glycoproteins in human milk and in gastric aspirates of mother's
      milk-fed preterm infants.
AB  - Human milk fat globule (HMFG) glycoproteins can prevent infections by
      microorganisms in breast-fed infants; the MUC-1 mucin inhibits binding of S
      fimbriated Escherichia coli to buccal mucosa, and lactadherin may prevent
      symptomatic rotavirus infections. In this study, the survival of these HMFG
      glycoproteins in the stomach of human milk-fed preterm infants (gestational age =
      27.5 +/- 0.4 wk) was assessed, and levels in their mothers' milk determined,
      using specific RIAs. Butyrophilin, a major component of HMFG membrane that has no
      demonstrated antimicrobial activity, was studied for comparison. The levels of
      mucin, lactadherin, and butyrophilin in 41 milk samples of 20 mothers were 729 +/
      75, 93 +/- 10, and 41 +/- 3 microg/mL, respectively. Mucin and lactadherin were
      significantly higher in early milk samples (<15 d postpartum) than in later milk
      samples (15-90 d postpartum), whereas butyrophilin showed no such difference.
      Significant amounts of mucin and lactadherin were found in almost all gastric
      aspirates of human milk-fed infants, even 4 h after feeding (mucin, 270 +/- 30
      microg/mL; lactadherin, 23.2 +/- 4.4 microg/mL), whereas butyrophilin was rapidly
      degraded in the majority of aspirates. Western blot analysis demonstrated that
      the immunoreactive mucin, lactadherin, and butyrophilin in the milk-fed gastric
      aspirates had the expected native molecular weights. Mucin and lactadherin
      survived at all gastric pH values, whereas butyrophilin was found only at pH > 4.
      Neither lactadherin nor butyrophilin were detected in gastric aspirates of
      formula-fed infants (gestational age = 27.8 +/- 0.5 wk), whereas the very low
      level of mucin (9.1 +/- 1.1 microg/mL) in this group is presumably cross-reacting
      gastric mucin. These results demonstrate that two HMFG glycoproteins implicated
      in prevention of infection, MUC-1 mucin and lactadherin, survive and maintain
      their integrity in the stomachs of human milk-fed preterm infants.

PMID- 9773838
TI  - Iron absorption and red blood cell incorporation in premature infants fed an iron
      fortified infant formula.
AB  - This study was designed to identify differences in red blood cell (RBC)
      incorporation and iron absorption in premature infants between iron provided in a
      premature infant formula compared with iron provided as a supplement between
      feedings. We used a triple stable isotope technique in which 13 infants received
      57Fe mixed with Enfamil Premature Formula on d 1 of the study, and 54Fe with a
      multivitamin supplement between meals on d 2. Two weeks later, blood was drawn
      for isotope analysis and 58Fe was given i.v. The percentage RBC incorporation of
      the 54Fe and 57Fe was calculated, and the percent absorption of these tracers was
      estimated by dividing by the percentage of 58Fe identified in RBCs 14 d after its
      infusion. We found a small, but significantly greater, percentage of RBC
      incorporation of the 54Fe given as a supplement compared with the 57Fe given in
      the formula (9.7 +/- 3.8% versus 7.8 +/- 3.1%, p = 0.02). The RBC 57Fe
      incorporation was closely correlated with the reticulocyte count (r = 0.80, p =
      0.001), but not the serum ferritin or the Hb concentration. Approximately 68% of
      an i.v. dose of 58Fe was incorporated into RBCs. These findings indicate 1) iron
      is incorporated well into RBCs from preterm infant formula, with only a small
      increase in incorporation when given as a supplement, and 2) the reticulocyte
      count, but not the Hb concentration, is a good measure of RBC iron-incorporating
      capacity.

PMID- 9773839
TI  - Rat milk and dietary long arginine3 insulin-like growth factor I promote
      intestinal growth of newborn rat pups.
AB  - Newborn rat pups were artificially reared by the pup in cup (PIC) method to
      determine whether dietary long arginine3 IGF-I (long R3 IGF-I), an IGF-I analog
      with high receptor affinity and low IGF binding protein (IGFBP) affinity, had
      efficacy on intestinal growth. IGF effects are mediated by IGFBP and receptor
      interactions, hence dietary-induced changes in intestinal IGF-II receptor
      patterns and IGFBP-3 message levels were investigated. Intestinal micrographs of
      pups fed rat milk replacer (RMR) for 3 d showed flattened villi with low cell
      counts and appeared similar to newborn intestines. Mother-fed (MF) controls and
      long R3 IGF-I-fed pups showed increased villi height and cell counts when
      compared with RMR pups, with long R3 IGF-I fed pups showing the greatest
      increase. At birth IGF-II-specific binding was not uniform in the intestine;
      specific binding was higher in the proximal intestinal section than in the distal
      intestinal section. However, after 3 d of MF treatment, specific binding had
      reversed and the distal section showed higher IGF-II-specific binding. Three days
      of RMR feeding did not change IGF-II-specific binding from that of the newborn
      pup. An IGFBP-3 message was identified in intestinal epithelium by in situ
      hybridization. Northern analysis of IGFBP-3 message showed a decline over time,
      but the change was not influenced by dietary treatments. In summary, milk-borne
      growth factors have the potential to affect intestinal growth within 3 d of
      treatment.

PMID- 9773840
TI  - Early feeding, antenatal glucocorticoids, and human milk decrease intestinal
      permeability in preterm infants.
AB  - To determine the effects of age, feeding regimen, and antenatal glucocorticoids
      on intestinal permeability, preterm infants (n = 132) were stratified by
      gestational age and by diet (mothers' own milk versus preterm formula), and
      assigned randomly to one of four feeding regimens: early-continuous, early-bolus,
      standard-continuous, and standard-bolus. At 10, 28, and 50 d of age permeability
      was determined by measuring the ratio of lactulose/ mannitol in the urine after
      the two sugars were administered enterally for 30 h. The mean (+/-SE) birth
      weight and gestational age of the infants were 1044 +/- 13 g and 27 +/- 0.1 wk,
      respectively. Permeability changed as a function of age (p = 0.003). Early
      feeding was associated with a reduction in permeability at 10 d of age (p =
      0.01). Antenatal steroid administration was associated with decreased
      permeability at 28 d of age (p = 0.017). The feeding of human milk (versus
      formula) was associated with decreased permeability at 28 d of age (p = 0.02).
      Continuous versus bolus feeding did not affect permeability.

PMID- 9773841
TI  - Transforming growth factor-beta levels in maternal milk and expression in
      postnatal rat duodenum and ileum.
AB  - After birth, the gastrointestinal tract of the neonate is exposed to food and
      bacterial and environmental antigens. Maternal milk components may play a role in
      regulation of mucosal immune activity to luminal antigens. In this study we
      determine the ontogeny of transforming growth factor (TGF)-beta1-producing cells
      in the rat pup small intestine and assess maternal milk concentrations of TGF
      beta. Intestinal tissue samples of duodenum and ileum were collected, processed,
      and stained for TGF-beta1, and in situ hybridization for TGF-beta1 mRNA was also
      performed on the duodenum. TGF-beta levels in milk were assayed by ELISA. TGF
      beta2 levels in milk were high at d 6, and declined thereafter at d 10 and 19.
      TGF-beta1 was not detected. In contrast, the cell number and intensity of
      staining of TGF-beta1 peptide in the small intestine was low in 3- and 10-d-old
      rats and increased markedly by 19 d of life. In the duodenum mRNA levels mirrored
      this trend. TGF-beta1 expression in the lamina propria was absent before d 19,
      and increased progressively over time. Maternal milk TGF-beta2 levels are high in
      early milk and decrease during the weaning period. In contrast, endogenous TGF
      beta production in the small intestine increases during the weaning period.

PMID- 9773842
TI  - Placental transport of leucine and lysine is reduced in intrauterine growth
      restriction.
AB  - Intrauterine growth restriction (IUGR) is characterized by a reduction in fetal
      plasma concentrations of a number of essential amino acids. Whether this is
      caused by impaired placental transport is unknown. We studied transport of
      leucine and lysine in syncytiotrophoblast microvillous (MVM) and basal membrane
      (BM) vesicles isolated from uncomplicated (control) and IUGR pregnancies. In
      addition, we investigated the possibility that leucine uptake is stimulated by an
      outwardly directed glycine gradient. Uptake of 3H-L-lysine (0.1 microM) and 3H-L
      leucine (0.25 microM) was studied at 37 degrees C using rapid filtration
      techniques. In IUGR, mediated uptake of lysine was reduced by 44% (p < 0.05) in
      BM and uptake of leucine was lower in both MVM (-46%, p < 0.05) and BM (-38%, p <
      0.05) compared with control vesicles. Intravesicular glycine (2 mM) increased the
      uptake of leucine by 98% in MVM (p < 0.05). These data suggest that the activity
      of placental transporters for cationic and neutral amino acids is reduced in
      IUGR. We speculate that a reduced glycine gradient in the placenta in IUGR, due
      to reduction in system A activity, will impair leucine transport to the fetus,
      providing an additional mechanism for reduced placental transport of leucine in
      IUGR.

PMID- 9773843
TI  - Effects of environmental exposure to polychlorinated biphenyls and dioxins on
      birth size and growth in Dutch children.
AB  - Lower birth weight and growth retardation has been found in studies with
      laboratory animals, in children born of mothers exposed to accidental high levels
      of polychlorinated biphenyls (PCBs) and related compounds, and in children born
      of mothers who consumed PCB-contaminated fish. The effect of background exposure
      to PCBs and dioxins on birth size and growth in human newborns, however, is still
      unknown. This study examined birth size and postnatal growth of term newborns in
      relation to their background PCB and dioxin exposure. Birth weight and weight,
      length, and head circumference were measured at 10 d and 3, 7, 18, and 42 mo of
      age in 207 children, of whom 105 were breast-fed and 102 were formula-fed during
      infancy. The effect of in utero exposure to PCBs on birth size, assessed by cord
      and maternal plasma PCB levels, was investigated in the whole group. The effect
      of prenatal PCB exposure on postnatal growth was studied in the formula-fed
      group, whereas the effect of prenatal as well as lactational exposure to PCBs and
      dioxins on postnatal growth was studied in the breast-fed group. After adjustment
      for covariates, cord and maternal plasma PCB levels where both negatively
      associated with birth weight. Infants with high cord plasma PCB levels (P90 =
      0.80 microL) weighed 165 g less compared with infants with low cord plasma PCB
      levels (P10 = 0.20 microg/L). Cord and maternal plasma PCB levels where both
      significantly associated with lower growth rate, defined as change in SD score
      (SDS) of weight, length, and head circumference from birth to 3 mo in the formula
      fed group (all p values <0.05). No negative effects of prenatal PCB exposure on
      growth rate were found from 3 to 42 months of age. Postnatal PCB and dioxin
      exposure was not negatively associated with growth rate in the breast-fed group.
      In utero exposure to environmental levels of PCBs is negatively associated with
      birth weight and postnatal growth until 3 mo of age. Although this growth delay
      was described in healthy term born infants, intrauterine and postnatal growth
      retardation are potentially harmful to the developing human and should be avoided
      by reducing maternal PCB and dioxin body burden, and consequently fetal exposure
      to these pollutants.

PMID- 9773844
TI  - Influence of restricted maternal nutrition in early to mid gestation on placental
      and fetal development at term in sheep.
AB  - We investigated the influence of restricted maternal nutrition between 28 and 77
      d of gestation on placental weight and appearance, and on fetal weight and
      conformation. Single-bearing ewes were fed either twice [i.e. controls (n = 19)]
      or half [i.e. nutrient-restricted (n = 28)] their energy requirements from 28 to
      77 d of gestation, after which all ewes were fed to fully meet the energy
      requirements for maintenance and pregnancy. Close to term (145 +/- 1 d) placental
      weight was higher in the nutrient-restricted group [nutrient-restricted, 416.3 +/
      12.6 g; controls, 347.4 +/- 17.6 g (p < 0.01)], as was the abundance of everted
      placentomes. There was no significant difference in total fetal weight, or
      weights of individual organs between groups, but crown-rump length was
      significantly greater in lambs born to nutrient-restricted ewes [nutrient
      restricted, 50.4 +/- 0.4 cm; controls, 48.2 +/- 0.6, cm (p < 0.01)]. Fetal to
      placental weight ratio was lower in the nutrient-restricted group [nutrient
      restricted, 9.51 +/- 0.23; controls, 10.81 +/- 0.39 (p < 0.01)]. A stronger
      relationship between the total weight of the fetal component of the placental and
      fetal weight was observed in controls (r2 = 0.50) than in nutrient-restricted
      ewes (r2 = 0.18). In conclusion, maternal nutrient restriction over the period of
      rapid placental growth results in a larger placenta and altered placental to
      fetal weight ratio if ewes are subsequently fed to requirements for the remainder
      of gestation.

PMID- 9773845
TI  - Biphasic increase in serum inhibin B during puberty: a longitudinal study of
      healthy Finnish boys.
AB  - We investigated the concentrations of serum inhibin B and the pro-alphaC
      containing inhibins (pro-alphaC inhibin) and their relations to serum FSH levels
      in 38 healthy boys during their progression through puberty. Furthermore, we
      studied the effect of recombinant human FSH (rhFSH) on pro-alphaC inhibin
      production in three prepubertal gonadotropin-deficient boys. The serum inhibin B
      level increased between Tanner stages G1 and G2 (p < 0.02), simultaneously with
      the serum LH and testosterone concentrations. In advanced puberty, inhibin B
      changed less, and at stage G4, correlated negatively with serum FSH level (r = 
      0.57, p < 0.001, n = 37). The serum pro-alphaC inhibin level changed differently
      and increased also in advanced puberty. In prepubertal healthy subjects, the
      serum pro-alphaC inhibin and FSH levels correlated positively (r = 0.50, p =
      0.051, n = 16), and during the rhFSH treatment of gonadotropin-deficient boys,
      serum pro-alphaC inhibin levels increased. These findings suggest that an
      increased production of inhibin B is an early event in puberty and that inhibin B
      can inhibit pituitary FSH secretion in the course of sexual maturation.
      Furthermore, they suggest that during puberty free inhibin (pro)-alpha-subunits,
      detected by the pro-alphaC inhibin assay, are present in large amounts and that
      FSH stimulates their production by prepubertal testes.

PMID- 9773846
TI  - Reduced energy expenditure in preobese children treated for acute lymphoblastic
      leukemia.
AB  - Children with acute lymphoblastic leukaemia (ALL) typically gain weight at
      excessive rates during and after therapy, and a high proportion of young adult
      survivors are obese. Previous studies have failed to identify the abnormalities
      in energy balance that predispose these children to obesity. The aim of this
      study was to determine the cause of excess weight gain in children treated for
      ALL by testing the hypothesis that energy expenditure is reduced in these
      patients. Twenty children [9 boys, 11 girls; mean age 10.9 (3.2) y] treated for
      ALL who had shown excess weight gain, but were not obese [mean body mass index SD
      score 0.70 (1.04)], were closely and individually matched with 20 healthy control
      children [9 boys, 11 girls; mean age 10.7 (3.0) y; mean body mass index SD score
      0.27 (0.91)]. In each child we measured total energy expenditure by doubly
      labeled water method, resting energy expenditure, energy expended on habitual
      physical activity, and energy intake. Total energy expenditure was significantly
      higher in control subjects than in patients: mean paired difference 1185 kJ/d
      (282 kcal/d), 95% confidence interval (CI) 218-2152. This difference was largely
      due to reduced energy expended on habitual physical activity in the patients.
      Resting energy expenditure was lower in the patients: mean paired difference 321
      kJ/d (76 kcal/d), 95% CI 100-541. Energy intake was also lower in the patients:
      mean paired difference 1001 kJ/d (238 kcal/d), 95% CI 93-1909. Children treated
      for ALL are predisposed to excess weight gain, and subsequently obesity, by
      reduced total energy expenditure secondary to reduced habitual physical activity.
      Prevention of obesity in ALL should focus on modest increases in habitual
      physical activity, modest restriction of dietary intake, and monitoring of excess
      weight gain.

PMID- 9773847
TI  - Target height as predicted by parental heights in a population-based study.
AB  - The corrected midparental height method was introduced by Tanner in 1970 (Tanner
      method) and is commonly used to estimate target height in children to evaluate
      the effectiveness of growth-promoting therapies. It has not been established if
      the equation used to compute target height should be the same for children with
      short, normal, or tall parents. In this study, we examined the predicted target
      height values by parental heights in a large population-based study (n = 2402). A
      simple linear function of midparental height (x) was proposed to estimate target
      height (y): y = 45.99 + 0.78x (boys), y = 37.85+0.75x (girls), with a 95%
      predicted interval of about +/-10 cm. The prediction model was similar for boys
      and girls in SD scores (SDS), and was not affected by assortative mating or
      difference in parental heights. The model may underestimate the potential stature
      by about 2 cm for children with midparental height below -2 SDS, or 163 cm. In
      comparison, the Tanner method may lead to a 6-cm error in underestimating target
      height for these children. The function would be a better choice than the Tanner
      method for estimating target height in the clinical evaluation of growth
      promotion treatments because it is common that short children also have short
      parents. Children with very short parents will usually be much taller than their
      parents in adult stature, and we believe that a different function should be
      developed. The results support the proposed nondominant, non-sex-linked,
      polygenic inheritance in stature. The estimated heritability values were 0.75
      0.78 in cm or 0.55-0.60 in SDS.

PMID- 9773848
TI  - Description and evaluation of a method based on magnetic resonance imaging to
      estimate adipose tissue volume and total body fat in infants.
AB  - Information about body fatness is important during nutritional assessment of
      infants, but current methods to estimate body composition in vivo are often not
      applicable in infants. Therefore, a new method based on magnetic resonance
      imaging (MRI) was developed. This method, which can assess the volume and
      distribution of adipose tissue (AT) as well as total body fat, was applied in 11
      healthy full-term infants. Their total body water was also estimated using the
      isotope dilution technique. Adipose tissue volume (ATV) was calculated from AT
      area in 16 images of the body taken by an MRI scanner (1.5 tesla). AT area was
      assessed using a computer program in which AT criteria was defined by the
      observer. ATV of the infants was therefore evaluated once by three observers and
      twice by a fourth observer. The different observers estimated total, s.c., and
      non-s.c. ATV with a precision that varied between 1.9 and 7.2%, 2.0 and 4.8%, and
      4.2 and 40.7%, respectively. Variations during AT area calculations accounted for
      a large part of the imprecision when assessing total and s.c. ATV. The linear
      relationship between percent total body water and total ATV in relation to body
      weight was significant in all evaluations. Although average total ATV varied when
      estimated by the four observers, there was, within each evaluation, a fairly
      constant order between infants with respect to their ATV. It is concluded that
      the MRI procedure represents a useful possibility to assess body fatness in
      infants.

PMID- 9773849
TI  - Visual activation in infants and young children studied by functional magnetic
      resonance imaging.
AB  - The purpose of this study was to determine whether visual stimulation in sleeping
      infants and young children can be examined by functional magnetic resonance
      imaging. We studied 17 children, aged 3 d to 48 mo, and three healthy adults.
      Visual stimulation was performed with 8-Hz flickering light through the sleeping
      childs' closed eyelids. Functional magnetic resonance imaging was performed with
      a gradient echoplanar sequence in a l.5-T magnetic resonance scanner. Six
      subjects were excluded because of movement artifacts; the youngest infant showed
      no response. In 10 children, we could demonstrate areas of signal decrease during
      visual stimulation in the occipital cortex (mean decrease 2.21%), contrary to the
      signal increase observed in the adult controls (mean increase 2.82%). This
      decrease may be due to a higher proportional increase in oxygen extraction
      compared with increase in cerebral blood flow during activation. The different
      response patterns in young children and adults can reflect developmental or
      behavioral differences. Localization of the activation seemed to be age
      dependent. In the older children and the adults, it encompassed the whole length
      of the calcarine sulcus, whereas it was restricted to the anterior and medial
      part of the calcarine sulcus in the younger infants. This may reflect a different
      functional organization of the young child's visual cortex or the on-going
      retinal development.

PMID- 9773850
TI  - Microstructural development of human newborn cerebral white matter assessed in
      vivo by diffusion tensor magnetic resonance imaging.
AB  - Alterations of the architecture of cerebral white matter in the developing human
      brain can affect cortical development and result in functional disabilities. A
      line scan diffusion-weighted magnetic resonance imaging (MRI) sequence with
      diffusion tensor analysis was applied to measure the apparent diffusion
      coefficient, to calculate relative anisotropy, and to delineate three-dimensional
      fiber architecture in cerebral white matter in preterm (n = 17) and full-term
      infants (n = 7). To assess effects of prematurity on cerebral white matter
      development, early gestation preterm infants (n = 10) were studied a second time
      at term. In the central white matter the mean apparent diffusion coefficient at
      28 wk was high, 1.8 microm2/ms, and decreased toward term to 1.2 microm2/ms. In
      the posterior limb of the internal capsule, the mean apparent diffusion
      coefficients at both times were similar (1.2 versus 1.1 microm2/ms). Relative
      anisotropy was higher the closer birth was to term with greater absolute values
      in the internal capsule than in the central white matter. Preterm infants at term
      showed higher mean diffusion coefficients in the central white matter (1.4 +/-
      0.24 versus 1.15 +/- 0.09 microm2/ms, p = 0.016) and lower relative anisotropy in
      both areas compared with full-term infants (white matter, 10.9 +/- 0.6 versus
      22.9 +/- 3.0%, p = 0.001; internal capsule, 24.0 +/- 4.44 versus 33.1 +/- 0.6% p
      = 0.006). Nonmyelinated fibers in the corpus callosum were visible by diffusion
      tensor MRI as early as 28 wk; full-term and preterm infants at term showed marked
      differences in white matter fiber organization. The data indicate that
      quantitative assessment of water diffusion by diffusion tensor MRI provides
      insight into microstructural development in cerebral white matter in living
      infants.

PMID- 9773851
TI  - Near infrared spectroscopy detects cerebral ischemia during hypotension in
      piglets.
AB  - We have previously reported concordant changes in cerebral intravascular
      oxygenation measured by near infrared spectroscopy (NIRS) and mean arterial blood
      pressure (MAP) in premature infants. We hypothesized that the cerebral
      oxygenation changes are caused by MAP-induced alterations in cerebral blood flow
      (CBF) and studied these parameters in neonatal piglets (n = 6). Changes in
      cerebral intravascular oxygenation were measured by NIRS from the hemoglobin
      difference (HbD) signal (oxyhemoglobin-deoxyhemoglobin). CBF was measured by the
      radioactive microsphere technique. The cerebral circulation was also monitored by
      Doppler determinations of CBF velocity (time average mean velocity) in the
      anterior cerebral artery. Hypotension to <50% of baseline MAP was achieved by a
      ligature around the ascending aorta. Arterial oxygenation was maintained constant
      by mechanical ventilation. As observed in our studies of premature infants,
      cerebral HbD and MAP showed concordant changes. Hypotension was accompanied by
      significant decreases both in CBF (42.8 +/- 12.5% of baseline p < 0.01) and HbD (
      65.0 +/- 22.0 micromol/L x dpf, p < 0.01). HbD was significantly correlated with
      MAP (p < 0.05) and time average mean velocity (p = 0.01). Importantly, decreases
      in cerebral total hemoglobin (HbT), a measure of cerebral blood volume, did not
      correlate significantly with decreases in MAP. We conclude that 1) decreases in
      cerebral intravascular oxygenation, as assessed by NIRS, observed with decreases
      in MAP reflect a decline in CBF, and hence oxygen delivery, 2) the HbD signal is
      more sensitive to changes in CBF than the HbT signal, and 3) NIRS recordings may
      have clinical utility in detecting cerebral ischemia.

PMID- 9773852
TI  - Increased serum levels of vascular endothelial growth factor in Kawasaki disease.
AB  - Vascular endothelial growth factor (VEGF) is an angiogenic mitogen that
      specifically targets vascular endothelial cells. The objective of this study was
      to evaluate the role of VEGF in Kawasaki disease (KD), the most common cause of
      systemic vasculitis in childhood. Serum VEGF levels were measured by ELISA in 22
      patients with KD, 22 febrile children with infection, and 19 healthy children.
      Samples from KD patients were divided into three groups: acute stage (n = 20),
      subacute stage (n = 13), and convalescent stage (n = 15). The results showed that
      KD patients in the acute and subacute stages had significantly higher levels of
      VEGF than did patients with infectious diseases and the healthy control subjects.
      When compared with the VEGF levels of patients with and without coronary artery
      lesions (CAL), significantly higher levels of VEGF were observed in the subacute
      stage in patients with CAL and in patients without CAL in the acute stage. Serial
      examination revealed that the serum VEGF levels in KD patients with CAL increased
      from a relatively low level in the acute stage to an extremely high level in the
      subacute stage. In contrast, patients without CAL were found to have extremely
      high levels of VEGF only in the acute stage of KD. In KD patients, the serum VEGF
      levels did not correlate with the inflammatory markers and clinical symptoms. Our
      results raise the possibility that VEGF is involved in the pathogenesis of KD,
      especially in the development of CAL. Further study is needed to clarify the
      biologic effect of VEGF on coronary arteries in KD.

PMID- 9773853
TI  - Influence of age and low afterload on the stress-velocity relation of the left
      ventricle.
AB  - The relation between systolic meridional wall stress (WS) and velocity of
      circumferential fiber shortening (VcFc) is widely accepted as a preload
      independent index of contractility, with a linear relation in most subjects older
      than 2 y. However, this relation seems to become different in infants and after
      administration of inotropic agents. We decided to study the nature of the stress
      velocity relation by a cross-sectional assessment of the influence of age, low
      afterload, and increased contractility. Study subjects were 30 healthy infants,
      32 healthy older children, and 35 asymptomatic older children after completion of
      anthracycline chemotherapy. WS and VcFc at rest were studied in these infants and
      children. WS and VcFc were also studied after dobutamine infusion in both groups
      of older children. Linear regression analysis of the stress-velocity relation
      showed parallel slopes between the older children at rest and the post
      anthracycline children after dobutamine. The regression lines between the infants
      at rest and the healthy older children after dobutamine were also parallel, but
      with a different and steeper slope compared with the former groups. When
      comparing the stress-velocity relation of the overall population at rest with the
      overall population after dobutamine, the resulting regression lines are
      curvilinear and parallel, with a steeper slope at low afterload. The stress
      velocity relation in infants and after dobutamine, resulting in low afterload is
      different compared with the stress- velocity relation in older children at rest
      and at higher afterload. Data of the overall population at rest and after
      dobutamine suggest a curvilinear relation.

PMID- 9773854
TI  - Velocardiofacial syndrome patients with a heterozygous chromosome 22q11 deletion
      have giant platelets.
AB  - Patients with a microdeletion on chromosome 22q11 demonstrate the clinical
      picture of the velocardiofacial syndrome. We report on three members of the same
      family with this microdeletion and velocardiofacial syndrome, all having an
      increase in platelet size and a mild decrease in platelet number. Their platelet
      function, however, tested by aggregation and by adherence to collagen in a whole
      blood perfusion system, was normal. We retrospectively studied the files of 35
      other patients with 22q11 deletion and also found that their platelets had an
      increased size compared with cardiac controls. Moreover, their platelet size
      correlated negatively with platelet number. Knowing that patients with 22q11
      deletion are obligate carriers for a heterozygous glycoprotein Ib beta deletion,
      these patients can be considered to be heterozygous Bernard-Soulier patients. In
      addition, a significant increase in platelet size may be a positive predictor for
      the clinical diagnosis of the velocardiofacial syndrome.

PMID- 9773855
TI  - Optimum maintenance trough levels of cyclosporine in heart transplant recipients
      given corticosteroid-free regimen.
AB  - BACKGROUND: Standard immunosuppressive therapy for heart transplant recipients
      consists of cyclosporine, azathioprine, and corticosteroids. Long-term use of
      steroids results in serious side effects. Steroid-free maintenance
      immunosuppressive regimens have been shown to be safe and effective in selected
      heart transplant recipients. Cyclosporine is the cornerstone of immunosuppressive
      therapy in such regimens. The ideal dose of cyclosporine, providing adequate
      immunosuppression while minimizing toxicity, remains controversial in the
      standard triple immunosuppressive regimen. This study attempted to define the
      optimal level of cyclosporine (whole blood radioimmunoassay) for heart transplant
      recipients given a steroid-free regimen. METHODS: We retrospectively analyzed
      data from 583 endomyocardial biopsies and corresponding cyclosporine trough
      levels obtained from 48 orthotopic heart transplant recipients maintained without
      steroids. We used maximum likelihood probit techniques to examine the correlation
      between cyclosporine level and the probability of rejection (International
      Society for Heart and Lung Transplantation [ISHLT] grades higher than 1A). The
      data were adjusted for age at the time of transplantation, sex, race, time
      elapsed since transplantation, and azathioprine dose. RESULTS: Higher
      cyclosporine levels were associated with a lower probability of acute cellular
      rejection (p < .03). The lowest probability of rejection, ISHLT grades higher
      than 1A (1.7%), was associated with a cyclosporine level of 322 ng/mL. In this
      database, higher levels of cyclosporine were not associated with higher serum
      creatinine levels (p = .6). CONCLUSIONS: Cyclosporine trough levels of 300 to 350
      ng/mL (whole blood radioimmunoassay) are associated with the lowest probability
      of cellular rejection in patients given a steroid-free regimen of cyclosporine
      and azathioprine. There was no association between cyclosporine levels and serum
      creatinine.

PMID- 9773856
TI  - Late acute rejection and subclinical noncompliance with cyclosporine therapy in
      heart transplant recipients.
AB  - BACKGROUND: Although noncompliance with immunosuppressive medication is
      recognized as a critical behavioral risk factor for late acute rejection episodes
      and graft loss after transplantation, little is known about the degree of
      subclinical cyclosporine noncompliance, its associated risk for acute late
      rejection episodes (>1 year after transplantation), and its determinants in heart
      transplant recipients. METHODS: The convenience sample of this longitudinal study
      included 101 European heart transplant recipients (87 men and 14 women), with a
      median age of 56 (Q1 = 50, Q3 = 61) and a median posttransplantation status of 3
      (range 1 to 6) years. Subclinical cyclosporine noncompliance was measured during
      a 3-month period with electronic event monitoring. Selected sociodemographic,
      behavioral, cognitive, emotional, health, and treatment-related determinants of
      medication noncompliance were measured by using instruments with established
      psychometric properties or by patient interviews. With the use of iterative
      partitioning methods of cluster analysis, including nonstandardized electronic
      event monitoring compliance parameters, patients were categorized by degree of
      subclinical cyclosporine noncompliance into a 3-cluster solution. RESULTS:
      Overall compliance was high, with a median medication taking compliance of 99.4%.
      The 3 derived clusters, that is, excellent compliers (84%), minor subclinical
      noncompliers (7%), and moderate subclinical noncompliers (9%), differed
      significantly by degree of subclinical noncompliance (p < .0001) and showed a
      1.19%, 14.28%, and 22.22% incidence of late acute rejections (p = .01),
      respectively. The 3 groups also differed in terms of former medication
      noncompliance (p = .02), appointment noncompliance (p = .03), and perceived self
      efficacy with medication taking (p = .04). CONCLUSIONS: Although in absolute
      numbers cyclosporine compliance in this sample was high, minor deviations from
      dosing schedule were associated with an increased risk for acute late rejection
      episodes. This suggests a pivotal role of patient compliance in successful long
      term outcome after transplantation.

PMID- 9773857
TI  - Preliminary experience with mycophenolate mofetil used after lung
      transplantation.
AB  - This study reports our preliminary experience with mycophenolate mofetil (MMF)
      based immune suppression after lung transplantation. Thirteen patients (group 1)
      received MMF as primary therapy immediately after transplantation. Use of MMF was
      associated with a linearized rate of 0.85 episodes of acute rejection per 100
      patient days during the first 3 months after transplantation, as compared with
      rates of 1.49 and 1.38, observed in two groups of historical control subjects (p
      = .094 and p = .053, respectively). Rejection rates after the first 3 months were
      not lower than in historical control subjects. Nine additional patients were
      switched from azathioprine to MMF because of recurrent episodes of high-grade
      acute rejection (group 2). In this group, the linearized rate of acute rejection
      episodes declined significantly (p = .004) after initiation of MMF therapy. These
      data suggest a potential role for MMF in reducing the rate of acute rejection
      episodes after lung transplantation.

PMID- 9773858
TI  - The impact of cytolytic therapy on bronchiolitis obliterans syndrome.
AB  - BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the major cause of
      morbidity and death after lung transplantation. Therapy has focused on augmented
      immunosuppression with a variety of agents. Although transient responses are
      often achieved, sustained remission has been unusual. The outcome of cytolytic
      therapy for BOS at our center has been analyzed and is reported. METHODS: Between
      July 1988 and July 1994, 233 patients underwent lung transplantation at Barnes
      Jewish Hospital. Among 207 recipients (88.8%) who survived more than 3 months, 81
      recipients (39%) had development of BOS; 48 of these patients underwent 64
      courses of treatment with a cytolytic agent (antilymphocyte globulin,
      antithymocyte globulin, or OKT3 monoclonal antibody). The cases of BOS were
      retrospectively analyzed to determine the impact of cytolytic therapy. RESULTS:
      The 4-year survival rate was significantly greater in recipients without BOS than
      in those with BOS (82.8% vs 46.0%; p < .05). Various clinical factors, including
      diagnosis, forced expiratory volume in 1 second at onset of BOS, presence or
      absence of pathologically proven bronchiolitis obliterans, type of transplant
      operation, cytomegalovirus serologic status, and cytomegalovirus pneumonia, were
      examined, but no significant predictor of survival after the development of BOS
      was discerned. The mean decrement in forced expiratory volume in 1 second was
      significantly reduced by cytolytic therapy (-23.5% +/- 2.3% in the 3 months
      before therapy vs -9.9% +/- 3.5% in the 3 months after the therapy; p < .002).
      Nevertheless, the stage of BOS progressed over time in spite of therapy in most
      cases, and only 4 recipients (4.9%) with BOS remained in a lower BOS stage 2
      years after treatment. CONCLUSIONS: Recipients with BOS had a significantly lower
      survival rate than recipients without BOS. No predictor of survival after the
      onset of BOS was identified. Although cytolytic therapy decreased the rate of
      decline in pulmonary function in the 3 months after treatment, the stage of BOS
      ultimately progressed in most patients.

PMID- 9773859
TI  - Platelet transfusions are associated with the development of anti-major
      histocompatibility complex class I antibodies in patients with left ventricular
      assist support.
AB  - BACKGROUND: Preformed anti-human leukocyte antigen (HLA) antibodies delay heart
      transplantation in patients with left ventricular assist devices (LVAD) because
      of difficulty in finding crossmatch-negative donors. These antibodies may also be
      associated with adverse outcome after transplantation. METHODS: In a
      retrospective analysis of 40 patients with LVAD at Columbia-Presbyterian Medical
      Center between 1990 to 1996, age, sex, diagnosis, race, duration of support,
      transfusions, and infections were studied by univariate and multivariate analysis
      as predictors for development of either anti-HLA class I (anti-I) or anti-HLA
      class II (anti-II) immunoglobulin G (IgG) or M (IgM) antibodies. RESULTS:
      Eighteen (45%) patients had development of anti-I and 20 (50%) had development of
      anti-II antibodies over the study period. Median time for LVAD support was 142
      days (range 35 to 439). Only total number of perioperative platelet transfusions
      predicted the development of anti-I IgG antibodies (p = .04). No other
      associations were found for development of anti-I IgM or anti-II antibodies of
      either IgG or IgM specificity. Patients who had development of anti-I IgG
      received a mean of 13.9 (SE +/- 2.6) units of platelets compared with a mean of
      7.7 (SE +/- 2.3) units in those who did not (p = .01). By Kaplan-Meier analysis,
      at the median duration of follow-up, 8% of patients receiving < 6 units were
      predicted to have development of anti-I antibodies compared with 63% receiving >
      6 units (p = .002). In the last 7 patients, leukocyte filters were used to
      decrease the antigenic load during platelet and red blood cell transfusions. Only
      1 of 7 (14%) patients had development of anti-HLA antibodies compared with 31 of
      33 (94%) in whom filters were not used (p < .005). CONCLUSIONS: These results
      indicate that platelet transfusion during LVAD implantation is a risk factor
      associated with development of HLA class I IgG antibodies. Use of leukocyte
      filters during platelet transfusion may decrease the risk of development of anti
      HLA antibodies.

PMID- 9773860
TI  - RANTES chemokine expression is related to acute cardiac cellular rejection and
      infiltration by CD45RO T-lymphocytes and macrophages.
AB  - BACKGROUND: Despite the advances made in immunosuppression therapy, episodes of
      acute cellular rejection may affect graft function and survival. We investigated
      the role of RANTES in cellular recruitment and in cardiac allograft rejection.
      METHODS: Endomyocardial biopsies (n = 65) from 30 patients were taken at various
      times after transplantation. In 4 subjects who died of acute cellular rejection,
      the profile of RANTES expression was monitored in all biopsy specimens and in
      postmortem tissue. Myocardial tissue from 10 other transplants was also analyzed.
      Sections were stained with an anti-human RANTES antibody with the streptavidin
      biotin technique. RANTES-positive cells were related to macrophage, CD45RO
      "memory" T-cell, and eosinophil infiltration. RESULTS: RANTES-positive cells were
      identified within the cellular infiltrate in 95% of biopsies with moderate/severe
      rejection and 28% with mild rejection. RANTES-positive, CD45RO-positive, and
      macrophage cell numbers were higher in subjects who died of acute cellular
      rejection than of other causes. A highly significant difference in RANTES
      positive cell number was observed between moderate/severe, mild, and nonrejection
      groups (p = .0001) and correlated significantly with macrophage number in both
      right and left ventricles (r = .693, p < .01; r = .599, p < .05, respectively)
      and with the number of "memory" T cells (r = .829, p < .001; r = .779, p < .01,
      respectively). CONCLUSIONS: These findings suggest that local release of RANTES
      is important in the recruitment of both macrophages and CD45RO T cells in cardiac
      allograft rejection. RANTES may be an important chemokine to target for
      therapeutic intervention in heart rejection.

PMID- 9773861
TI  - Induction of donor-specific tolerance to cardiac xenografts in utero.
AB  - BACKGROUND: Problems associated with heart transplantation, such as shortage of
      suitable organs and the side effects of immunosuppressive therapy, are especially
      serious for patients in the pediatric age group. Induction of donor-specific
      immunologic tolerance without immunosuppressive drugs would be ideal for clinical
      organ transplantation. In this study, we used a vascularized cardiac xenograft
      model to achieve donor-specific unresponsiveness without immunosuppression by
      manipulating the intrauterine immune response. METHODS: Lewis rats and Golden
      Syrian hamsters were used as the recipients and donors, respectively. Donor bone
      marrow cells (15 x 10(6) in 0.05 mL) were injected into each fetus of pregnant
      Lewis rats on days 9 (n = 2) and 16 (n = 2) of gestation. Donor hearts were
      heterotopically transplanted into each surviving (n = 8, n = 5) fetus of the
      Lewis rats at 8 weeks of age. Donor hearts were also transplanted into untreated
      rats as controls (n = 8). RESULTS: The mean cardiac xenograft survival time was
      2.5 +/- 0.5, 7.4 +/- 4.1, and 2.8 +/- 0.8 days in the control group, gestational
      day 9 group, and gestational day 16 group, respectively. Chromosomal analysis of
      the day 9 group showed Golden Syrian hamster chromosomes as well as Lewis rat
      chromosomes. CONCLUSIONS: Cardiac xenograft survival was significantly prolonged
      by intrauterine exposure to xenograft bone marrow cells on day 9 but not on day
      16 of gestation. Cardiac xenograft survival and chromosomal analysis of the
      recipient bone marrow suggested that chimerism was achieved between Golden Syrian
      hamsters and Lewis rats. Cardiac xenotransplantation may be possible by induction
      of donor-specific tolerance in utero.

PMID- 9773862
TI  - Local relation between oxidative metabolism and perfusion in leg muscles of
      patients with heart failure studied by magnetic resonance imaging and
      spectroscopy.
AB  - BACKGROUND: We studied the local relation of muscle perfusion and metabolism in
      patients with severe chronic heart failure. Alterations of skeletal muscle blood
      flow and oxidative capacity contribute to exercise intolerance in these patients.
      The interdependence of both parameters has often been questioned. METHODS AND
      RESULTS: With the use of nuclear magnetic resonance, we quantified leg and muscle
      perfusion during reactive hyperemia in 7 patients with heart failure (New York
      Heart Association class III and IV) and 7 age-matched control subjects from the
      difference in longitudinal relaxation rate (1/T1). By using 31P nuclear magnetic
      resonance spectroscopy, we assessed oxidative metabolism from the creatine
      rephosphorylation time constant after a short ischemic exercise. Phosphocreatine
      recovery is slowed (74.6 +/- 11.3 vs 49.9 +/- 13.9 seconds, p = .002) and
      reactive hyperemic flow is reduced (48.5 +/- 24.9 vs 113 +/- 30.4 mL/100 mL per
      minute, p = .0005). CONCLUSIONS: By using a totally noninvasive protocol, we
      demonstrated that reactive hyperemic flow correlates with oxidative capacity in
      calf muscles from patients with heart failure, showing that exercise performance
      and local circulatory dysfunction are decreased in parallel in severe heart
      failure.

PMID- 9773863
TI  - Transplantation with older donor hearts for presumed "stable" recipients: an
      analysis of the Joint International Society for Heart and Lung
      Transplantation/United Network for Organ Sharing Thoracic Registry.
AB  - BACKGROUND: We have previously demonstrated that the use of older donor hearts
      (>45 years) increases the odds of death nearly twofold in the early
      posttransplantation period when compared with the use of hearts from younger
      donors. Before excluding this segment of the donor pool, however, the mortality
      risk for remaining on the waiting list compared with that of receiving an older
      donor heart should also be considered. METHODS: We examined all adult status 2
      patients added to the United Network for Organ Sharing heart transplant waiting
      list for primary transplantation between 1992 and 1995 (n = 4681). To account for
      the transient increased risk after transplantation, we used a time-dependent
      nonproportional hazards model with an exponential decay component for the
      analysis. For patients with an equal time since listing, the resulting risk
      ratios represent the ratio of mortality risk for a patient who receives an older
      donor heart to the mortality risk for a patient who remains on the waiting list.
      RESULTS: After 30 days posttransplantation, the risk of death for recipients of
      45- to 49-year-old donor hearts was lower than if they had remained on the
      waiting list, and by 6 months the relative risk was 0.37 (95% confidence
      interval: 0.22, 0.62). For recipients of hearts from donors 50 years or older,
      the risk after transplantation was lower after 64 days, and by 6 months the
      relative risk was 0.48 (95% confidence interval: 0.31, 0.75). CONCLUSION: These
      results suggest that in spite of a high initial risk resulting from the
      transplant procedure, there was a clear long-term survival benefit for status 2
      recipients of older donor hearts. Thus overall, in spite of the increased risk of
      death associated with receiving older donor hearts, the risk of death without a
      transplant was even greater. On the basis of this analysis we cannot support the
      exclusion of older donors from the donor pool.

PMID- 9773864
TI  - Long-term hemodynamic benefit of atrial synchronization with A2A2D or A2A2T
      pacing in sinus node syndrome after orthotopic heart transplantation.
AB  - BACKGROUND: Exercise capacity after heart transplantation (HTx) may be limited by
      sinus node disease of the donor heart and atrioatrial dissociation. The role of
      pacemaker therapy in this setting is not well defined. The purpose of this study
      was to compare clinical and hemodynamic data of heart transplant recipients with
      acquired sinus node disease treated with atrial synchronized pacing and patients
      with other pacing modes or without pacemakers 1 year after operation. METHODS:
      Our cohort comprises a total of 112 HTx recipients from the years 1984 to 1996.
      Atrial synchronized pacing was performed in 21 patients with donor sinus node
      disease and recipient sinus rhythm. There was no associated morbidity or death
      for the pacemaker implantation. Fourteen patients received a dual-chamber
      pacemaker programmed with a short atrioventricular-Delay in A2A2D mode (donor
      atrial pacing triggered by recipient atrial sensing or both atria stimulated on
      demand); in the last 6 consecutive patients a single-chamber pacemaker was
      implanted with two unipolar leads to the atria connected with a Y adapter
      programmed in A2A2T mode (both atria were sensed and stimulated by triggering
      each other). RESULTS: Signals and thresholds remain stable over time. When
      clinical and hemodynamic data of 12 A2A2D/T patients with complete 1 year follow
      up were compared to age- and sex-matched control HTx recipients with other pacing
      modes or without pacemakers, a significant benefit of atrial synchronization
      could be shown regarding rise in heart rate response to exercise (+38% vs 30% vs
      16% at 50 watt), New York Heart Association classification (1.6 vs 1.8 vs 2.2),
      Roskamm staging (1.3 vs 2.5 vs 1.5), cardiac index at rest (3.2 vs 2.78 vs 3.1
      L/min x m2), cardiac index at 50 watt (5.5 vs 4.5 vs 5.2 L/min x m2), stroke work
      at rest (51 vs 38 vs 42 pondmeter [PM]), stroke work at 50 watt (66 vs 48 vs 51
      PM), pulmonary wedge pressure at rest (7 vs 13 vs 8 mm Hg) and pulmonary wedge
      pressure at 50 watt (14 vs 24 vs 18 mm Hg). CONCLUSION: It is concluded that
      electromechanical synchronization of the atria was of long-term benefit in heart
      transplant recipients with recipient sinus rhythm and donor sinus node disease.

PMID- 9773865
TI  - Randomized trial of daily versus three-times-weekly prophylactic ganciclovir
      after lung and heart-lung transplantation.
AB  - BACKGROUND: Cytomegalovirus is an important cause of morbidity and mortality risk
      after lung transplantation. Ganciclovir, when given for a period of up to 3
      months after lung transplantation, has been shown to reduce the incidence and
      severity of cytomegalovirus. However, daily prophylaxis is associated with
      considerable expense, inconvenience, and morbidity risk. The goal of this study
      was to determine whether 3-times-weekly dosage is as effective as daily
      prophylaxis with ganciclovir in preventing cytomegalovirus disease. METHODS:
      Seventy-two consecutive subjects who had either donor or recipient
      cytomegalovirus seropositivity were randomized to the daily group (n = 35) or the
      3-times-weekly group (n = 37). All subjects received twice-daily ganciclovir
      treatment for 2 weeks. Thereafter, subjects received either daily or 3-times
      weekly ganciclovir dosing until 90 days after transplantation. Subjects were then
      monitored for 28 +/- 13 months to identify outcomes and complications. RESULTS:
      There were no significant differences between the daily and 3-times-weekly groups
      with respect to survival free from cytomegalovirus infection or survival free
      from cytomegalovirus disease. In both groups, cytomegalovirus infection and
      disease frequently emerged after the termination of prophylaxis. However, in most
      cases the cytomegalovirus syndromes observed were mild and in many cases could be
      treated on an outpatient basis. There was no significant difference between the
      groups in the incidence of obliterative bronchiolitis or time to onset of grade 2
      bronchiolitis obliterans syndrome. Overall patient survival was better in the
      daily group, but the survival advantage did not appear to be related to a
      reduction in cytomegalovirus-related disease. Complications of ganciclovir
      prophylaxis included leukopenia in 2 subjects in the 3-times-weekly group and
      catheter-related sepsis in 6 subjects from each group. CONCLUSIONS: We conclude
      that intravenous ganciclovir given 3 times weekly for 3 months after
      transplantation is as effective as daily ganciclovir given for a similar time
      period. The 3-times-weekly dosing regimen did not result in increased infection,
      disease, or sequelae of cytomegalovirus infection when compared with the daily
      regimen.

PMID- 9773866
TI  - Effects of brain death on myocardial function and ischemic tolerance of potential
      donor hearts.
AB  - BACKGROUND: An increasing number of experimental and clinical studies reports
      hemodynamic instability in the donor organism after brain death. However, the
      relative importance of brain death-related cardiac dysfunction on
      posttransplantation cardiac function and the reversibility of the observed
      changes remain controversial. In this study a load-independent analysis of
      cardiac function after brain death was performed. Special interest was focused on
      a possible interactive influence of brain death and cardiac preservation on
      postischemic cardiac function. METHODS: In 12 anesthetized dogs, brain death was
      induced by inflation of a subdural balloon; 12 sham-operated animals served as
      control subjects. After a 2-hour observation in situ, the hearts were explanted
      and perfused parabiotically either immediately or after hypothermic ischemic
      preservation (4 hours, 4 degrees C). Heart rate, cardiac output, left ventricular
      pressure, the maximum of left ventricular pressure development and aortic
      pressure were measured in situ. In addition, the slope of the end-systolic
      pressure-volume relationship, coronary blood flow, and myocardial oxygen
      consumption were estimated in the cross-circulated hearts. RESULTS: In spite of a
      brain death-associated hemodynamic deterioration in situ (expressed as low mean
      aortic pressure and significant decrease of maximal dP/dt), myocardial function
      was similar to control after explantation, if assessed ex vivo. Furthermore,
      after hypothermic ischemic preservation and reperfusion, complete functional
      recovery of control and brain-dead hearts could be observed. CONCLUSIONS: These
      data indicate that hemodynamic instability after brain death may rather reflect
      altered loading conditions than irreversible myocardial damage or primary cardiac
      dysfunction. Furthermore, there is no evidence for a brain death-related
      impairment of ischemic tolerance.

PMID- 9773868
TI  - Proceedings from three international conferences on quantitative fluorescence
      cytometry (QFCM).

PMID- 9773867
TI  - The effect of triiodothyronine on myocardial contractile performance after
      epinephrine exposure: implications for donor heart management.
AB  - BACKGROUND: This study analyzes in the experimental model of isolated human
      atrial myocardium whether the myocardial contractile depression occurring after
      high-dose/long-term catecholamine exposure (as typically occurring in brain-dead
      organ donors) can be reversed by thyroid hormone administration. METHODS:
      Isolated trabeculae were prepared from atrial myocardium from patients undergoing
      coronary artery bypass (n = 15). Initial measurements of isometric force were
      carried out (measurement conditions of 37 degrees C, Krebs Henseleit solution,
      supramaximal electrical stimulation, 1 Hz, at optimal length). Then the
      trabeculae were incubated for 6 hours at 26 degrees C in a Krebs Henseleit
      solution containing epinephrine 10(-7) mol/L and the fluorescent dye FURA-2/AM
      for calcium measurements. At the end of the incubation period, isometric force,
      isotonic shortening, and intracellular calcium transient (FURA-2 "ratio method")
      were measured. After 30 minutes administration of triiodothyronine (5 x 10(-9)
      mol/L), the measurements were repeated. Control groups included 6 hours
      incubation in 4 degrees C Krebs Henseleit solution (n = 5); 6 hours incubation in
      26 degrees C FURA-2/AM (n = 5); and 6 hours incubation in epinephrine 10(-7)
      mol/L (n = 5). RESULTS: After 6 hours catecholamine exposure isometric force
      declined significantly to 56.8% (p < .0001) and isotonic shortening to 54% of its
      initial value (p < .01). Administration of triiodothyronine was associated with a
      significant recovery of the isotonic shortening amplitude (p < .005), of
      isometric force development (p < .01), an increased velocity of force development
      (p < .0001), and of diastolic force decay (p < .005). At the same time the shape
      of the intracellular calcium transient became smaller as a result of an
      accelerated diastolic decay. The amplitude of the calcium transient remained
      unaltered, whereas the calcium time integral was reduced (p < .05). CONCLUSION:
      In the model of isolated human myocardium, experimental depression of the
      contractile performance resulting from long-term catecholamine exposure could be
      reversed by a 30-minute triiodothyronine incubation. The experimental data
      showing increased force amplitudes at unaltered amplitudes of the intracellular
      calcium transient and an even-reduced calcium time integral provide strong
      evidence for a sensitization of the contractile apparatus for calcium by
      triiodothyronine. The data provide additional knowledge to explain the successful
      administration of triiodothyronine in donor heart management.

PMID- 9773869
TI  - Terminology and nomenclature for standardization in quantitative fluorescence
      cytometry.
AB  - Terminology in any field is a complex mix of established conventions, accepted
      usages, disputed terms, and occasional misnomers. The terminology that has
      evolved for quantitative fluorescence cytometry (QFCM) is especially
      multifarious, in part because QFCM encompasses a range from subjective visual
      assessments to objective photon counts. Thus, while descriptive terms such as
      "dim" and "bright" are still quite useful, quantitative terms such as "binding
      capacity" should be used with collective understanding of their exact meanings.
      This article reviews current usage and proposes definitions that, with refinement
      from suppliers and users of QFCM technology, can provide the required clarity.

PMID- 9773870
TI  - Standardizing flow cytometry: a classification system of fluorescence standards
      used for flow cytometry.
AB  - The growing number of standards commercially available in the field of flow
      cytometry makes it difficult to know which standards to use to obtain a desired
      level of quality assurance. A classification system of fluorescence standards has
      been developed on the basis of their physical characteristics. In turn, these
      physical characteristics determine the ability of the specific standards to
      perform selected functions, such as alignment, target referencing, compensation,
      and calibration. Knowing the properties and limitations of specific standards
      will help flow cytometer users to select the appropriate standard for the
      application that they will be performing, especially in regard to intra- and
      interlaboratory quality assurance. Common protocols used in conjunction with
      specific classifications of reference standards can provide unified analysis
      regions or window of analysis across different instruments and/or laboratories.
      In addition, specific classifications of calibration standards can help select
      those standards that will provide independent and direct comparison of instrument
      performance parameters, especially in studies involving multiple laboratories.
      Knowledge and understanding of the classification system can guide flow cytometer
      users in more efficient and accurate instrument setup and quality control when
      conducting research, as well as clinical applications.

PMID- 9773871
TI  - Indicators of T-cell activation: correlation between quantitative CD38 expression
      and soluble CD8 levels in asymptomatic HIV+ individuals and healthy controls.
AB  - Increased activation of CD8+ T cells, particularly increased expression of CD38
      antigen, has been shown to strongly correlate with progression of human
      immunodeficiency virus-positive (HIV+) individuals to acquired immunodeficiency
      syndrome (AIDS) and death. As part of a study evaluating responses to a
      recombinant gp160 vaccine, we have used quantitative three-color flow cytometry
      (QFCM) to further investigate the relationships among several measures of
      lymphocyte activation/immunological status. Parameters evaluated included 1)
      absolute circulating counts for the major lymphocyte phenotypes (T, B, NK) and
      selected activated/regulatory subsets believed to have clinical value in the
      monitoring of patients with HIV infection; 2) level of CD38 expression (antibody
      binding capacity [ABC]) on the lymphocyte subsets defined by CD8, CD38, and HLA
      DR; and 3) serum levels of soluble CD8. CD8+DR+CD38+ counts were found to be
      markedly increased (approximately 10-fold) in HIV+ individuals, whereas
      CD4+CD45RA+ counts were markedly decreased (approximately 5-fold). We confirmed
      previous reports that CD38 expression on CD8 T cells (here reported as CD38 ABC)
      are increased in asymptomatic HIV+ individuals as compared with healthy controls,
      and further found that CD38 ABC was elevated approximately 2-fold on CD8+DR+
      cells as compared with CD8+DR- cells in healthy controls, and almost 2-fold
      further elevated on CD8+DR+ cells in HIV+ individuals compared with CD8+DR+ cells
      in healthy controls. In agreement with previous studies, we found increased serum
      CD8 levels (sCD8) and increased CD8+DR+ counts in asymptomatic HIV+ individuals.
      However, when sCD8 was expressed relative to CD8+DR+ cell counts (RsCD8), this
      index was found to be significantly decreased in HIV+ individuals. Although CD38
      ABC on CD8+DR+ cells showed no correlation with sCD8, it was significantly
      correlated with RsCD8 in both HIV+ and HIV- individuals. Absolute lymphocyte
      counts were strongly correlated with both CD38 ABC and RsCD8 in HIV+ individuals.
      However, CD4 counts were correlated with CD38 ABC (but not RsCD8) in HIV+
      patients and with RsCD8 (but not CD38 ABC) in HIV-controls. Our results suggest
      that QFCM is significant in understanding the role of CD8+DR+CD38+ cells in
      processes such as lymphocyte homeostasis and HIV-induced CD4-cell depletion.

PMID- 9773872
TI  - Quantitation of CD38 activation antigen expression on CD8+ T cells in HIV-1
      infection using CD4 expression on CD4+ T lymphocytes as a biological calibrator.
AB  - For some membrane-associated antigens, the number of molecules expressed per cell
      carries information about the cell's differentiation and activation state.
      Quantitating antigen expression by flow cytometry has immediate application in
      monitoring CD38 expression on CD8+ T cells in human immunodeficiency virus 1
      associated disease, where elevated CD38 antigen expression is a marker of CD8+ T
      cell activation and a poor prognostic indicator. Reproducible methods are needed
      in order to quantify such antigens. Here we describe a reproducible method for
      quantitative fluorescence cytometry (QFCM) that depends on the tightly regulated
      expression of CD4 antigen on human CD4+ T lymphocytes, which we estimated in a
      study of 57 normal donors to have an interperson coefficient of variation of
      4.9%. Using phycoerythrin (PE)-conjugated CD4 monoclonal antibody (mAb) with a
      nominal fluorochrome to protein ratio of 1:1 and a nominal published value of
      approximately 50,000 CD4 antibody molecules bound per CD4+ T lymphocyte, we
      estimated the number of PE molecules detected per relative fluorescence intensity
      (RFI) unit on our flow cytometer to be 41 (19, 20). This value is called the "RFI
      multiplier." To estimate the number of CD38 antibodies bound per CD8+ T cell
      (CD38-ABC) on patient samples, we multiply the measured CD38 RFI value of CD38
      staining using a nominal 1:1 conjugate of CD38-PE by the "RFI multiplier." The
      measurements for CD4 and CD38 were stable for 2 years despite the use of
      different mAb lots and the potential for drift in instrumentation. We used this
      approach in a study of nine flow cytometers in which the interinstrument
      interlaboratory coefficients of variation for CD3-ABC ranged from 3.3% to 5.8%
      and those for CD38-ABC ranged from 9.8% to 13.8%. These data indicate that CD4
      expression can serve as a biological calibrator to standardize fluorescence
      intensity measurements in longitudinal and multicenter studies.

PMID- 9773873
TI  - CD38 expression on cryopreserved CD8+ T cells predicts HIV disease progression.
AB  - Previous studies have revealed that the expression of CD38 on CD8+ T cells is a
      strong predictor of disease progression in human immunodeficiency virus (HIV)
      infected individuals. Those studies were performed using fresh patient samples
      over an extended trial period. After demonstrating the validity of assay results
      on cryopreserved cells, we performed a retrospective study using frozen cell
      samples to determine the predictive value of CD38 expression in patients with CD4
      counts above 400 cells/microl. The CD38 expression as measured by antibody
      binding capacity and the CD38 median channel were shown to be associated with
      time to new opportunistic infection or death (both P < 0.001). These results
      suggest that CD38 expression on CD8+ T cells, whether fresh or frozen, provides a
      useful predictor of HIV disease progression.

PMID- 9773874
TI  - Quantitative flow cytometry: inter-laboratory variation.
AB  - Quantitative flow cytometry (QFCM) offers a means of standardization within and
      between flow cytometers. QFCM parameters were set by determining the antibody
      binding capacity (ABC) of CD4, CD8, and CD3 cells from 10 normal donors with the
      use of eight FACScan flow cytometers. QC3 beads and a certified blank bead were
      used to set up the instruments. Fluorescein isothiocyanate (FITC) conjugated to
      molecular equivalents of soluble fluorochrome (MESF) microbead standards was used
      before and after the donor samples were run to ensure that the machines were
      operating consistently. Lyophilized cells (Cytotrol) were used as a target, to
      control for antigen expression in the cell preparation. Quantitative Simply
      Cellular (QSC) beads were used to establish a standard calibration curve for each
      of the FITC and phycoerythrin antibody conjugates on each of the instruments.
      Single-parameter fluorescent histograms derived from list-mode files were used to
      calculate the slope (coefficient of response), intercept (zero channel), number
      of channels per decade, and ABC or MESF threshold (blank bead). The fluorescence
      intensity (geometric mean) of the positive and negative donor cell populations
      was compared with the standard curves, and the ABCs were calculated. The results
      show consistent instrument performance between laboratories. However, after
      standardization of CD3, CD4, and CD8 ABCs to microbeads, large variations were
      noted between donors and laboratories. The source of this variation does not
      appear to be in the instrumentation but may be due to the lack of an unified set
      up protocol, introducing issues of antibody saturation, methods for whole blood
      lysis and fixation, and the behavior of the microbead standards.

PMID- 9773875
TI  - Impact of unified procedures as implemented in the Canadian Quality Assurance
      Program for T lymphocyte subset enumeration. Participating Flow Cytometry
      Laboratories of the Canadian Clinical Trials Network for HIV/AIDS Therapies.
AB  - The objective of the Canadian Quality Assurance Program (CQAP) is to provide the
      most reproducible and accurate T-cell subset enumeration for individuals living
      with HIV who are enrolled in the Canadian Clinical Trial Network for Human
      Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS)
      Therapies (abbreviated as CTN). The Canadian National Laboratory for Analytical
      Cytology, within the Laboratory Centre for Disease Control, is part of the Health
      Protection Branch of Health Canada. For the past eight years, the Laboratory for
      Analytical Cytology has been responsible for delivering a bilingual quality
      assurance program for CD4 T-cell enumeration. This federal program, which
      integrates biotechnology transfer with quality assessment, was achieved through
      the organization of workshops focused on technology transfer and essential skill
      building techniques. Two training sessions were conducted for the CTN flow
      cytometer operators. The first introduced the concept of window of analysis, to
      demonstrate the practical benefits of unified quantitative fluorescent
      measurement. As a follow-up to the first workshop, participants performed a
      series of quantitative assays that monitored the expression of CD69, an early
      activation marker. This quantitative fluorescence protocol was performed with
      acceptable inter-laboratory variation using modified commercial kits. The second
      workshop focused on a absolute count method based on a single platform. Four
      preserved whole-blood preparations were tested with this approach. The combined
      effort reduced inter-laboratory variation. The direct impact was monitored as
      related to the frequency of participation. Over the years, the standard deviation
      of average accumulated variation decreased dramatically with increased frequency
      of participation, from 10% to <4%.

PMID- 9773876
TI  - Multi-platform, multi-site instrumentation and reagent standardization.
AB  - As flow cytometry laboratories involve themselves in more multi-site domestic and
      international clinical trial and research studies, it becomes imperative that
      they develop and adopt qualitative and quantitative standardization. This
      standardization does not need to be at the instrument-design level but it may
      evolve from a general consensus on instrument setup, internationally accepted
      standardized procedures, and quantitative fluorescence intensity units.
      Instrument condition, age, and setup as well as model and manufacturer all affect
      the overall instrument performance and quantitative characteristics. Therefore,
      when working with multiple instruments, platforms, or sites, a standard window of
      analysis is essential. Furthermore, we should strive to characterize instrument
      performance and quantitative indices so that data can be compared directly. The
      same thoughts and ideals hold true for standardizing procedures and reagents.
      Clones, conjugation, incubation times, pH, temperature, and other environmental
      conditions all combine to affect the qualitative and quantitative cellular
      indices that we are attempting to measure. Data are presented that illustrates
      why standardization is needed and how we have attempted to achieve it in our
      laboratories.

PMID- 9773877
TI  - Flow cytometric quantitation of immunofluorescence intensity: problems and
      perspectives. European Working Group on Clinical Cell Analysis.
AB  - Quantitation of immunofluorescence intensity serves to estimate the number of
      defined molecules expressed on or in cells. Clinical applications of this
      diagnostic tool are increasing, e.g., aberrant expression of various antigens
      (Ag) by leukemic blasts or lymphoma cells, intensity of CD38 expression by CD8+ T
      lymphocytes to monitor activation status, and intensity of CD62P to detect
      platelet activation. In this report we discuss the quality-control measures
      required for quantitation of fluorescence intensity, and we review seven concepts
      that have been developed to quantify fluorescence intensity during the past 15
      years. Initial work addressed the conversion of logarithmic channel numbers into
      units of relative fluorescence. The design and use of calibration beads labeled
      with predefined amounts of dye allowed instrument-independent expression of
      fluorescence intensity in units of molecules of equivalent soluble fluorochrome
      (MESF). This method was refined by the combined use of such standards with
      monoclonal antibodies (mAb) conjugated 1:1 with phycoerythrin (PE), allowing
      translation of fluorescence intensity into numbers of antibodies bound per cell.
      Alternatively, the use of 1:1 PE-conjugated mAb under the assumption that CD4+
      lymphocytes reproducibly bind 50,000 CD4 mAb molecules was proposed to convert
      units of relative fluorescence intensity into units of antibodies bound per cell.
      The use of antibody-binding capacity as a surrogate marker for quantification of
      Ag expression was addressed more directly by the development of antibody-binding
      standards. The quantitative indirect immunofluorescence assay is based on beads
      labeled with various amounts of CD5 mAb that calibrate the binding of the
      secondary antibody in units of antibody-binding capacity. Alternatively, goat
      anti-mouse-labeled calibration beads have been developed. Published results
      obtained with the latter calibrators showed an unexpected inaccuracy. The
      different ways in which calibrators and cells under study bind mAb (i.e., Fab
      mediated versus Fc mediated) may have contributed to this variation. Recently,
      the use of stabilized cell populations expressing Ag in a specified range of
      concentrations has been proposed as an Ag-specific calibration system of mAb
      binding. We identify several issues on the level of instrumentation, reagents,
      and cells under study that should be solved to allow standardization of
      quantitative assessments of immunofluorescence intensity.

PMID- 9773878
TI  - Quantitative fluorescence flow cytometry: a comparison of the three techniques
      for direct and indirect immunofluorescence.
AB  - Three types of microbead calibrators available for quantitative fluorescence flow
      cytometry have been studied in parallel using a variety of monoclonal antibodies
      (MoAbs). The QIFI kit is designed for indirect immunofluorescence (IF), and both
      the Quantum Simply Cellular (QSC) assay and the Quanti-BRITE assay are designed
      for direct IF. Because of the different nature of the respective ligands,
      epitopes on cells versus F'ab-portions on QSC beads, large differences in
      titration curves for a large number of CD MoAbs were noted between QSC beads and
      cells. Use of the QSC assay and fluorescein isothiocyanate (FITC) and
      phycoerythrin (PE) conjugates of the same CD reagent revealed substantially
      different numbers of cellular binding sites. Numbers of cellular binding sites as
      determined by direct IF using the Quanti-BRITE assay and by indirect IF using the
      QIFI kit were similar. We also found that erythrocyte (RBC)-lysing reagents cause
      varying and sometimes substantial reduction in the fluorescence intensity (FI) of
      cells stained directly with CD34 MoAb conjugates, but the RBC-lysing reagents had
      no effect on the FI of cells stained indirectly with the same CD34 MoAbs. This
      report defines a number of variables critical for standardized quantitative flow
      cytometry. We conclude that the choice of calibrators, fluorochrome conjugates,
      staining methods, and modes of sample processing can effect the determination of
      cellular binding sites to MoAbs. Direct immunofluorescence using the Quanti-BRITE
      assay and indirect IF using the QIFI kit appear to yield comparable results for
      the standardized determination of numbers of cellular binding sites to MoAbs.

PMID- 9773879
TI  - Performance of calibration standards for antigen quantitation with flow
      cytometry.
AB  - In the frame of the activities initiated by the Task Force for Antigen
      Quantitation of the European Working Group on Clinical Cell Analysis (EWGCCA), an
      experiment was conducted to evaluate microbead standards used for quantitative
      flow cytometry (QFCM). An unified window of analysis (UWA) was established on
      three different instruments (EPICS XL [Coulter Corporation, Miami, FL], FACScan
      and FACS Calibur [Becton Dickinson, San Jose, CA]) with QC3 microbeads (FCSC,
      PR). By using this defined fluorescence intensity scale, the performance of
      several monoclonal antibodies directed to CD3, CD4, and CD8 (conjugated and
      unconjugated), from three manufacturers (BDIS, Coulter [Immunotech], and DAKO)
      was tested. In addition, the QIFI system (DAKO) and QuantiBRITE (BDIS), and a
      method of relative fluorescence intensity (RFI, method of Giorgi), were compared.
      mAbs reacting with three more antigens, CD16, CD19, and CD38 were tested on the
      FACScan instrument. Quantitation was carried out using a single batch of
      cryopreserved peripheral blood leukocytes, and all tests were performed as single
      color analyses. Significant correlations were observed between the antibody
      binding capacity (ABC) values of the same CD antigen measured with various
      calibrators and with antibodies differing in respect to vendor, labeling and
      possible epitope recognition. Despite the significant correlations, the ABC
      values of most monoclonal antibodies differed by 20-40% when determined by the
      different fluorochrome conjugates and different calibrators. The results of this
      study indicate that, at the present stage of QFCM consistent ABC values may be
      attained between laboratories provided that a specific calibration system is used
      including specific calibrators, reagents, and protocols.

PMID- 9773880
TI  - Determination of CD4 antigen density on cells: role of antibody valency, avidity,
      clones, and conjugation.
AB  - The number of R-phycoerythrin (R-PE)-conjugated antibodies bound to a cell can be
      quantitated on a flow cytometer by using beads with known numbers of attached R
      PE molecules (QuantiBRITE PE). Using these reference beads, we have observed that
      a number of factors affect the accuracy of the quantitation and conclusions about
      epitope density. These factors include valence of antibody binding, the use of
      antibody fragments (Fab's) versus intact monoclonal antibodies (mAb's), fixation,
      the purity of the conjugate (i.e., percentage of 1:1 ratios), dissociation rate,
      the use of washed versus unwashed preparations, and the location of epitope on
      target antigen. We used CD4 on T cells as a model to explore these challenges in
      detail. We conclude that CD4+ T cells bind approximately 49,000 CD4 (Leu 3a)
      antibody molecules, that this binding is bivalent, and therefore that there are
      approximately 98,000 CD4 antigen molecules on the surface of these cells.

PMID- 9773881
TI  - Quantitation of CD38 expression using QuantiBRITE beads.
AB  - The QuantiBRITE bead method was compared with the CD4 biological calibration
      method for quantitation of CD38 expression on CD8+ T-lymphocytes of Multicenter
      AIDS Cohort Study participants. Results were expressed as CD38 antibodies bound
      per cell (ABCs) and were the same with the two methods provided two conditions
      were met. These were the use of repurified (> 95% of the monoclonal antibodies
      [mAbs] have 1 phycoerythrin [PE] molecule per mAb) CD38-PE for both methods and
      use of repurified CD4-PE to calculate the relative fluorescence intensity
      multiplier for the CD4 biological calibration method. Our results indicate that
      the prognostic significance of CD38 values obtained using the QuantiBRITE method
      can be interpreted using previously published reports (Liu et al.: J Acquir
      Immune Defic Syndr Hum Retrovirol 16:83-92, 1997 and 18:332-340, 1998). Sample
      preparation using NH4Cl and FACS lysing solution gave similar results for CD38
      relative fluorescence intensity. Dilution into either phosphate-buffered saline
      with 2% fetal calf serum and 0.1% sodium azide or fixation in 1% paraformaldehyde
      for 1 or 24 h also gave similar results. In experiments using Raji cells, which
      express high levels of CD38, the valence of binding of the intact Leu 17 antibody
      was approximately 68% bivalent and approximately 32% monovalent. This emphasizes
      the complexity of determining antigen density from ABCs. We conclude that
      repurified PE conjugates of CD38, which can be consistently made, together with
      QuantiBRITE PE beads, provide a convenient and reliable method for quantitation
      of CD38 expression as ABCs.

PMID- 9773882
TI  - Inter-laboratory relative fluorescence intensity measurements using FlowCal 575
      calibration beads: a baseline study.
AB  - Twenty-one laboratories participated in a baseline study of their ability to
      agree on the measurement of fluorescence intensities of a stable multi-peak
      reference material (FlowCal 575) and of stained and fixed CD4 lymphocytes.
      Relative fluorescence intensities were calculated as ratios to the most
      fluorescent bead. The good correlation between laboratories suggests that this
      simple approach may be useful in multi-laboratory studies. The data also provide
      a baseline for the evaluation of any improvement of inter-laboratory agreement
      gained by more rigorous and demanding approaches.

PMID- 9773883
TI  - Titration of a CD45-FITC conjugate to determine the linearity and dynamic range
      of fluorescence intensity measurements on lymphocytes.
AB  - To produce biologic calibrators for relative fluorescence intensity (RFI)
      measurements, we stained leukocytes with serial dilutions of CD45-FITC conjugate
      and processed them using our regular whole blood lysis procedure. Cells were
      stained with conjugate concentrations ranging from twice recommended to a million
      fold lower. At the highest concentrations of conjugate, the RFI reached a plateau
      near the top of the third decade, indicating saturation of CD45 binding sites. As
      the concentration decreased, the RFI declined in a highly linear relationship
      between the dilution factor and the histogram channel number. For channel numbers
      corresponding to the lowest percentiles of the RFI distribution, linearity
      persisted down to the first half decade. The slope of this relationship revealed
      a true dynamic range of 4.5 decades, which was comparable to the value obtained
      with microbead standards calibrated in molecules of equivalent soluble
      fluorochrome (MESF). Our results suggest that the lower limit of linearity for
      fluorescence intensity from fluorescein isothiocyanate (FITC)-stained lymphocytes
      is below 500 MESF and that cellular autofluorescence is the major limiting factor
      in detecting and quantifying FITC-specific staining. This procedure provides an
      adroit way of characterizing the linearity and dynamic range of measurements for
      quantitative fluorescence cytometry using exactly the same matrix, stains, and
      preparation methods as those used for cellular analytes.

PMID- 9773884
TI  - Supramolecular receptor structures in the plasma membrane of lymphocytes revealed
      by flow cytometric energy transfer, scanning force- and transmission electron
      microscopic analyses.
AB  - Receptors in the plasma membrane of blood cells in general and in that of
      lymphocytes in particular are supposed to move around in a random walk fashion
      relatively freely driven by thermal diffusion, as described by the Singer
      Nicolson fluid mosaic membrane model. In this article we summarized data and
      techniques that indicated nonrandom codistribution patterns of receptor
      superstructures under conditions, where the generation of such molecular
      colocalizations by the methods themselves were excluded. Application of
      fluorescence energy transfer in a flow cytometer helped to analyze such
      codistribution patterns in cell populations. After normalizing energy transfer
      values for possible differences between labeling ratios of the targeting
      monoclonal antibodies and using the mean values of energy transfer distribution
      curves, two-dimensional receptor maps were generated from data obtained in a pair
      wise fashion between receptors. Major histocompatibility complex (MHC) class I
      and II, intercellular adhesion molecule-1 (ICAM-1), TcR-CD3-CD4, tetraspan
      molecules (CD81, CD82, CD53), and the subunits of the multisubunit IL-2 receptor
      displayed nonrandom codistribution patterns sometimes with, but very frequently
      without induction by their ligand. Immunogold-bead "sandwich" labeling analyzed
      by atomic force microscopy has shown that such receptor "islands" existed also in
      "receptor-island-groups". This indicated the existence of nonrandom receptor
      distribution of MHC class I and II molecules also at an elevated hierarchical
      level. An analysis is given herein concerning a standardized approach. The
      apparent incompatibility of these supramolecular patterns with the Singer
      Nicolson type "free-protein and lipid-mobility paradigm" was resolved by
      recommending an additional emphasis on the mosaicism of the membrane besides
      receptor mobility.

PMID- 9773885
TI  - Classification and properties of 64 multiplexed microsphere sets.
AB  - We describe a practical method for the analysis of multiple analytes in a single
      sample. The vehicle for each separate measurement consists of a set of
      microspheres identifiable by characteristic fluorophores embedded in the
      particles. The use of robust, bench-top flow cytometers (flow microfluorimeters)
      for the analysis of the multiple sets of microspheres is facilitated by hardware
      and software, which acquire the data from the cytometer, classify the
      microspheres according to sets, and collate measurement information from each
      microsphere set in real time. This measurement system can analyze up to 64
      analytes in a single sample. The advantages of multiplexed assays using flow
      cytometry include robust measurements, because each microsphere set is measured
      repeatedly. The advantage of the assay's is consistent with simultaneous
      measurement of many parameters as well as the speed with which the flow
      microfluorimeter (cytometer) makes measurements (many hundreds per second). Here,
      we describe the properties of the microspheres, the calibration of the cytometer,
      and the influence of the properties of the microspheres on the sensitivity of
      measurements.

PMID- 9773886
TI  - Novel flow cytometry compensation standards: internally stained fluorescent
      microspheres with matched emission spectra and long-term stability.
AB  - In flow cytometry, the emission spectral overlap of fluorescein and R
      phycoerythrin is usually corrected by electronic color compensation using
      microspheres surface labeled with the same fluorochromes. However, the inherent
      chemical instability of these fluorochromes may cause inaccurate compensation. To
      overcome these problems, Compen-Flow beads, a new type of compensation standards
      were developed. The CompenFlow beads are a set of 6.0-microm-diameter polystyrene
      microspheres that are internally stained with selected BODIPY dye combinations.
      When excited by the 488-nm argon laser line, these beads show a nearly perfect
      emission spectral match to fluorescein-stained, R-phycoerythrin-stained and
      unstained lymphocytes, respectively. Moreover, since the dye molecules are oil
      soluble, they are contained inside the microsphere matrix instead of merely on
      the surface; thus, the molecules are shielded from environmental factors that
      could affect an exposed fluorochrome. Our results show a stable fluorescence
      spectral profile and constant intensity for at least 2 years stored either
      refrigerated or at room temperature.

PMID- 9773888
TI  - Evaluating fluorescence sensitivity on flow cytometers: an overview.
AB  - The current paradigms for assessing fluorescence sensitivity on flow cytometers
      do not provide an adequate assessment of an instrument's ability to detect and
      measure weak fluorescence on stained particles. The capability to resolve dimly
      stained populations depends on two factors: the background noise (B), and the
      efficiency (Q) with which the fluorescence from the fluorochrome molecules are
      converted to photoelectrons. Any single statistical measure of fluorescence
      histogram distributions will be unable to uniquely characterize an instrument.
      Therefore, neither of the routinely used methods (detection threshold and delta
      channel) measure sensitivity completely and unambiguously. We show the
      limitations of these methods and propose that instrument sensitivity be
      characterized in terms of both background noise and detection efficiency in order
      to determine better the capability to detect and resolve weakly fluorescent
      particles.

PMID- 9773887
TI  - T-lymphocyte functionality assessed by analysis of cytokine receptor expression,
      intracellular cytokine expression, and femtomolar detection of cytokine secretion
      by quantitative flow cytometry.
AB  - Assessing the functionality of T lymphocytes is important in determining
      progression rate in human immunodeficiency virus (HIV) infection and acquired
      immunodeficiency syndrome (AIDS), transplant rejection, and autoimmune disease.
      Activation of T-cells in response to antigen results in expression of cytokines
      and cytokine receptors, proliferation, and development of effector function.
      Multiplexed flow cytometric analyses were developed to measure cytokine receptor
      expression, internal cytokine expression, and cytokine secretion by activated T
      cells in vitro. Receptor expression was determined by the binding of
      phycoerythrin-labeled cytokines. Internal cytokine was determined by
      intracellular labeling with anti-cytokine antibodies. Cytokine secretion was
      determined by a flow cytometry-based immunofluorescence assay. The assays could
      be multiplexed, measuring up to six cytokines simultaneously and measuring
      cellular receptor expression simultaneously with cytokine secretion. The
      immunoassays were sensitive in the femtomolar range, allowing determination of
      normal serum levels of cytokines (<100 fg/ml). Using granulocyte-macrophage
      colony-stimulating factor (GM-CSF) secretion as a marker for activation, it was
      determined that at peak secretion (68 h post activation) an average of 1,150
      molecules of GM-CSF were produced per cell per hour. Active infection with
      several viruses reduced the ability of T-cells to be activated. Activated T-cells
      (1 x 10(6)) normally produced 4-8 pg/ml/h GM-CSF after 20 h of activation,
      impaired T-function resulted in a decrease to the 0.2-2.0 pg/ml/h range.

PMID- 9773889
TI  - Fundamental flow cytometer properties governing sensitivity and resolution.
AB  - The fundamental properties of a flow cytometer that govern its capacity to detect
      and resolve dim fluorescent particles are 1) the efficiency with which it can
      convert a photon emitted by a fluorochrome into a photoelectron at the
      photocathode of the photomultiplier tube and 2) the amount of optical background
      noise that is collected along with the fluorescence emission from the particle.
      Either of these properties alone is insufficient to predict an instrument's
      performance. Thus, to characterize a flow cytometer, both of these properties
      need to be determined. To determine these properties, one must not only consider
      the optical characteristics of the instruments but also understand the impact of
      the signal processing on the data collected. After the collection efficiency and
      the optical background noise level are determined, it is possible to predict the
      instrument's performance. A specific flow cytometer performance level is not
      unique to only one pair of these properties. To achieve a specific level of
      instrument performance, whole families of pairs of these properties are possible.

PMID- 9773890
TI  - Resolution of dimly fluorescent particles: a practical measure of fluorescence
      sensitivity.
AB  - Flow cytometry is usually used to analyze subpopulations of cells, not simply to
      measure the mean fluorescence level of a mixture. Thus, resolution or coefficient
      of variation (CV) of dimly stained populations is the most appropriate measure of
      fluorescence "sensitivity." Methods used to measure sensitivity that are in
      routine use do not unambiguously and completely determine the ability of a flow
      cytometer to resolve dimly fluorescent populations from each other. Since
      fluorescence sensitivity depends on two factors, background light (B) and
      detection efficiency (Q, the detected photoelectrons per fluorochrome molecule on
      an analyzed particle), one cannot uniquely define the operating condition of a
      flow cytometer with just one of these factors. In general, it is not possible to
      define the ability of a flow cytometer to resolve dim subpopulations by using a
      single number such as "noise level" or "detection threshold"-the description
      requires a "two-parameter" measure. A carefully characterized flow cytometer was
      used to determine the inherent fluorescent CV of dimly fluorescing beads. The
      fluorescence from the beads is also calibrated in terms of molecules of
      equivalent soluble fluorophore (MESF). The beads with known inherent CV and MESF
      provide a standard against which the instrument contribution to the CV of dim
      fluorescence can be measured. By measuring the standard deviation (SD) of the
      fluorescence histogram from unstained beads (noise) we obtain a second measure of
      instrument performance. The bead CV and noise SD are a sufficient pair of factors
      to determine the optical capability of a flow cytometer to resolve dim
      subpopulations of particles. It is also possible to use the measurements to
      calculate B and Q and use this information to predict the shapes of fluorescence
      histogram distributions of dim particles.

PMID- 9773891
TI  - A flow cytometer designed for fluorescence calibration.
AB  - In the development of suitable standards and calibration materials for
      fluorescence measurement, it becomes necessary to make accurate fluorescence
      measurements of these materials on flow cytometers. The results of such
      measurements may be affected by numerous sources of error, prominent among which
      are deviations of logarithmic amplifiers (log amps) from ideal response. To
      minimize the deleterious effects of log amps and multicolor fluorescence
      compensation circuitry on measurements, we built a flow cytometer with
      electronics incorporating high-precision peak detectors usable over a range from
      below 2 mV to 10 V, and we developed data acquisition software that transfers
      held peak values to a commercial 16-bit data acquisition system mounted in a
      personal computer running Windows 95. Fluorescence compensation is done in
      software, and transformation of the compensated data from a 16-bit linear to an 8
      bit, 4-decade logarithmic scale is accomplished using a look-up table. Although
      dynamic range may be restricted by noise in the data acquisition system, high
      sensitivity can be achieved by photomultiplier tube gain adjustment, and it is
      likely that the use of a lower noise data acquisition system and/or digital
      processing of pulse information will enable operation over the full 4-decade
      dynamic range. Even at its current performance level, our instrument provides
      substantially better linearity over most of the scale than can be obtained using
      conventional electronics incorporating log amps; we believe this characteristic
      is critical for use in standards development.

PMID- 9773892
TI  - A comparison of two U.S. Air Force pilot aptitude tests.
AB  - BACKGROUND: The Air Force Officer Qualifying Test (AFOQT) and Multidimensional
      Aptitude Battery (MAB) were administered to 2233 U.S. Air Force pilot candidates
      to investigate the common sources of variance in those batteries. The AFOQT was
      operationally administered as part of the officer commissioning and aircrew
      selection testing requirement. The MAB is a clinical test battery and was
      administered to provide an intellectual baseline to assist clinicians when it
      becomes necessary to evaluate pilots with cognitive referral questions. RESULTS:
      A joint factor analysis of the AFOQT and MAB revealed that each battery had a
      hierarchical structure. The higher-order factor in the AFOQT previously had been
      identified as general cognitive ability (g). The intercorrelation between the
      higher-order factors from the batteries was 0.981, indicating that both measured
      g. Although both batteries measured g and included verbal, spatial, and
      perceptual speed tests, the AFOQT also included tests of aviation knowledge not
      found in the MAB. CONCLUSION: Additional studies are required to evaluate the
      utility of the AFOQT for clinical assessment and the MAB for officer and aircrew
      selection.

PMID- 9773893
TI  - Sodium chloride-citrate beverages attenuate hypovolemia in men resting 12 h at
      2800 m altitude.
AB  - BACKGROUND: The mechanism for reduction and restoration of total body water and
      plasma volume (PV) during initial exposure to acute altitude (ALT) is not clear
      but may involve involuntary dehydration; i.e., delayed voluntary fluid intake.
      METHOD: Ten men (24 +/- SD 3 yr, 180.8 +/- 8.1 cm height, 78.8 +/- 12.8 kg
      weight, 1.99 +/- 0.19 m2 surface area, and 12.2 +/- 4.0% body fat) were in a semi
      reclining position for 12 h in a chamber at 2800 m (539 mmHg) ALT or at 321 m
      (732 mmHg; ground). They ate a controlled breakfast (450 kcal + 3 ml x kg(-1)
      H2O) on the ground, and lunch and dinner at ALT (or on the ground) for a total
      daily intake of 2850 kcal (14% PRO, 67% CHO, 16% fat, 2.6g NaCl). At hour 10 they
      consumed fluid-electrolyte beverages or water (12 ml x kg(-1), 948 ml x d(-1)) in
      4 sessions at weekly intervals. Beverage compositions were: a) 185 mEq x L(-1)
      Na+, 283 mOsm x kg(-1); b) 21.6 mEq x L(-1) Na+, 365 mOsm x kg(-1); c) water at
      ALT; and d) water on the ground. RESULTS: After 10 h at ALT % deltaPV (Hb-Hct)
      decreased (p < 0.05) by: a) 9.0 +/- SE 1.5%; b) 6.2 +/- 1.7%; c) 7.4 +/- 2.2%;
      and d) by 9.0 +/- 2.4%, respectively. After drinking from 1000-1030 h, PV at 1200
      h changed by: a) +8.3 +/- SE 2.0% (p < 0.05); b) +2.8 +/- 2.7% (NS); c) -0.9 +/-
      1.5% (NS); and d) by +0.8 +/- 3.5% (NS), respectively. The similar ground-induced
      hypovolemia suggests a response to confinement rather than an ALT effect and
      involuntary dehydration does not appear to be implicated. CONCLUSION: The
      significant increase in PV after consuming the (a) NaCl-NaCitrate beverage
      indicates that drink ionic composition appears to be more important than its
      osmolality for restoring PV in these conditions. Practical considerations:
      Because this hypovolemia was probably due to the confinement rather that reduced
      ambient pressure, appropriate countermeasures could be consumption of isotonic
      beverages, elastic stockings, leg exercise, and leg elevation.

PMID- 9773894
TI  - Cognition and aging in a complex work environment: relationships with performance
      among air traffic control specialists.
AB  - Chronological age affects the performance of demanding cognitive tasks within the
      aviation environment. Within the domain of air traffic control (ATC), the ability
      to handle simultaneous visual and auditory input, or to return to a task after a
      break to complete another task, is critical to success and is the sort of
      cognitive function most affected by age. The limited available data suggest a
      strong relationship between age and job performance among ATC specialists,
      whether measured at the time of entry into the system or during the working
      lifetime of a full-performance-level controller. An analysis of the distribution
      of the ages of controllers currently in the system, and a projection for the
      years 2001 and 2006, leads to the conclusion that a high proportion of the ATC
      work force will be at risk for displaying age-related changes in job performance
      efficiency over the next 10 yr. It seems important, therefore, to determine the
      nature and extent of the age-related cognitive changes that can occur during the
      lifespan of a controller (i.e., 25-55 yr of age) and how these changes may affect
      job performance. The results of such an analysis should aid in the design and
      implementation of new control systems to minimize any deleterious effects of
      aging on performance.

PMID- 9773895
TI  - Allergic rhinitis history as a predictor of other future disqualifying
      otorhinolaryngological defects.
AB  - BACKGROUND: Problems with the otorhinolaryngological system represent the largest
      category of pilot referrals for specialist assessment and possible waiver
      recommendation in the U.S. Navy. Most of these referrals deal with allergic
      rhinitis (AR). Approximately 3% of all Naval aircrew have a waiver for AR. This
      paper tests the hypothesis that the identification of a history of AR is a
      predictor for the development of future disqualifying otorhinolaryngological
      (ear, nose, and throat, or ENT) diseases such as chronic sinusitis, alternobaric
      disease, conductive hearing loss, or the need for various surgical procedures
      (i.e., Caldwell Luc antrostomy, myringotomy, polypectomy, mastoidectomy, and
      functional endoscopic sinus surgery. METHODS: The U.S. Navy Aviation Medical Data
      Retrieval System (AMDRS) was searched for aircrew who were diagnosed only with AR
      in 1988. These aircrew were matched with a control group from the 1988 database
      who had no diagnoses of AR or any of the other disqualifying ENT diseases. The AR
      cohort and controls had their physical examinations up to 1995 assessed to see if
      any of the disqualifying ENT conditions had developed. RESULTS: There was a
      statistically significant increase in the number of identifiable chronic
      sinusitis cases but there was no significant relationship between an AR history
      and the development of any of the other ENT disease categories. CONCLUSION: Based
      on the study findings, it is doubtful that uncomplicated AR as an isolated
      historical diagnosis should be disqualifying for either candidate or designated
      aircrew.

PMID- 9773896
TI  - The effect of wave motion on dry suit insulation and the responses to cold water
      immersion.
AB  - METHODS: Six subjects who were each wearing a dry immersion suit system were
      immersed for 1 h in 16 degrees C water in a number of different wave conditions,
      ranging from still water to 70 cm in height. Physiological and physical
      parameters were measured in order to calculate the total thermal resistance of
      the suit system and its components. RESULTS: None of the physiological parameters
      were affected significantly by the wave conditions, except for skin heat flux,
      which increased with wave height from 72.0 +/- 1.9 W x m(-2), at 0 cm of height,
      to 85.5 +/- 2.9 W x m(-2), at 70 cm of height. Wave heights up to 70 cm decreased
      the insulation (including boundary layer) of the dry suit system by 14%, and the
      only component of the suit affected by the wave motion was the insulation of the
      water boundary layer, which decreased by 75%. The body sites that were most
      affected by wave motion were the head and the trunk, with an average 45%
      decrement in suit system thermal resistance at those sites at wave heights of 0
      to 70 cm. No significant effect was observed at sites on the distal limbs.
      CONCLUSION: To simulate open ocean conditions in the laboratory, the standards
      must take the reduction of suit insulation into account.

PMID- 9773897
TI  - A loglogistic model for altitude decompression sickness.
AB  - BACKGROUND: Altitude decompression sickness (DCS) is a potential hazard
      encountered during high altitude flights or during extravehicular activity in
      space. In this study, the loglogistic distribution was used to model DCS risk and
      symptom onset time. METHODS: The Air Force Research Laboratory, Brooks AFB, TX,
      has conducted studies on human subjects exposed to simulated altitudes in
      hypobaric chambers. The dataset from those studies was used to develop the DCS
      models and consisted of 975 subject-exposures to various altitudes,
      preoxygenation times, and exercise regimens. Since the risk of DCS is known to
      increase over time at altitude, and then decrease because of denitrogenation, the
      loglogistic model was fit to the data. The model assumes that the probability of
      DCS depends on several risk factors. Maximum likelihood estimates of the
      parameters were obtained using the statistical software package SAS. Cross
      validation techniques were provided to examine the goodness of fit of the model.
      RESULTS: The fitted model indicated that altitude, ratio of preoxygenation to
      exposure time, and exercise were the most significant risk factors. The model was
      used to predict the risk of DCS for a variety of exposure profiles. The predicted
      probability of DCS agreed very closely with the actual percentages in the
      database. CONCLUSION: The loglogistic distribution was found to be appropriate
      for modeling the risk of DCS. Based on the cross validation and validation
      results, we conclude that this model provides good estimates of the probability
      of DCS over time.

PMID- 9773898
TI  - The mechanism of femoral fracture in an impact accident.
AB  - BACKGROUND: Following the crash of a Boeing 737-400 aircraft on the M1 motorway
      at Kegworth, near Nottingham, England, on January 8, 1989, it became apparent
      that a large number of pelvic and lower limb injuries had been sustained by the
      survivors. Had there been a fire, these injuries would have severely hindered the
      ability of the occupants to escape. The mechanism of pelvic and lower limb
      injuries in impact accidents previously has been related to flailing of the limbs
      and axial loading of the femur as in automobile accidents. HYPOTHESIS: A bending
      load is the primary mechanism of femoral fracture in an impact aircraft accident
      rather than an axial load. METHODS: Two methods of study have been used to
      investigate the impact biomechanics of the pelvis and lower limb: a) clinical
      review of the injuries sustained in the M1 Kegworth accident; and b) impact
      testing. RESULTS: A clinical review of the M1 aircrash survivors suggested that
      axial loading was not the primary mechanism causing femoral fractures and
      suggested that a bending load might be applied to the femur. Impact testing
      confirmed that axial loading of the femur did not appear to be significant.
      CONCLUSIONS: Our study suggests that in the presence of intact occupant
      protection systems, a femoral bending mechanism involving the front seat spar of
      passenger seats is a primary cause of femoral fracture in an impact aircraft
      accident.

PMID- 9773899
TI  - A modified crash brace position for aircraft passengers.
AB  - BACKGROUND: In 1989, a Boeing 737-400 aircraft crashed at Kegworth, near
      Nottingham, England. The survivors suffered a large number of pelvic and lower
      limb injuries, and approximately one-third of the passengers died. Subsequent
      research has suggested that the "brace-for-impact" position that passengers are
      advised to adopt prior to a crash landing might be modified in order to reduce
      the incidence of such injuries. The aim of this research was to evaluate
      biomechanically such a modified crash brace position. HYPOTHESIS: A modified
      brace position would help to prevent injuries to some passengers in the event of
      an impact aircraft accident. METHODS: Impact testing on forward-facing seats was
      performed at the Royal Air Force Institute of Aviation Medicine, Farnborough,
      England. Aircraft seats, mounted on a sled, were propelled down a track to impact
      at -16 Gx. A test dummy was used as the experimental model. Four dummy positions
      were investigated: a) upper torso braced forward and lower legs inclined slightly
      rearward of the vertical; b) upper torso braced forward and lower legs inclined
      forward; c) upper torso upright and lower legs inclined slightly rearward of the
      vertical; and d) upper torso upright and lower legs inclined forward. The impact
      pulses used were based on Federal Aviation Administration guidelines. Transducers
      located in the head, spine, and lower limbs of the dummy recorded the forces to
      which each body segment was exposed during the impact. These forces were compared
      for each brace position. RESULTS: Impact testing revealed that the risk of a head
      injury as defined by the head injury criterion was greater in the upright
      position than in the braced forward position. The risk of injury to the lower
      limbs was dependent in part on the flailing behavior of the limbs. Flailing did
      not occur when the dummy was placed in a braced, legs-back position. CONCLUSIONS:
      A modified brace position would involve passengers sitting with the upper torso
      inclined forward so that the passenger's head rested against the structure in
      front, if possible. The legs would be positioned with the feet resting on the
      floor in a position slightly behind the knee. The position differs from those
      previously recommended in that the feet are positioned behind the knee. This
      study suggests that such a position would reduce the potential for head and lower
      limb injury in some passengers, given that only a single seat type and single
      size of occupant have been evaluated. Standardization to such a position would
      improve passenger understanding and compliance. Such a recommendation should not
      obscure the fact that an occupant seated in a forward-facing aircraft seat,
      restrained only by a lap belt, is exposed to considerable forces during an impact
      accident. Such forces are capable of producing injuries in the femur, pelvis, and
      lumbar spine.

PMID- 9773900
TI  - Lung function during moderate hypobaric hypoxia in normal subjects and patients
      with chronic obstructive pulmonary disease.
AB  - BACKGROUND: We sought to describe changes in spirometric variables and lung
      volume subdivisions in healthy subjects and patients with chronic obstructive
      pulmonary disease (COPD) during moderate acute hypobaric hypoxia as occurs during
      air travel. We further questioned whether changes in lung function may associate
      with reduced maximum ventilation or worsened arterial blood gases. METHODS:
      Ambulatory patients with COPD and healthy adults comprised the study populations
      (n = 27). We obtained baseline measurements of spirometry, lung volumes and
      arterial blood gases from each subject at sea level and repeated measurements
      during altitude exposure to 8000 ft (2438 m) above sea level in a man-rated
      hypobaric chamber. RESULTS: Six COPD patients and three healthy subjects had
      declines in FVC during altitude exposure greater than the 95% confidence interval
      (CI) for expected within day variability (p < 0.05). Average forced vital
      capacity (FVC) declined by 0.123 +/- 0.254 L (mean +/- SD; 95% CI = -0.255, 
      0.020; p < 0.05) for all subjects combined. The magnitude of decline in FVC did
      not differ between groups (p > 0.05) and correlated with increasing residual
      volume (r = -0.455; <0.05). Change in maximum voluntary ventilation (MVV) in the
      COPD patients equaled -1.244 +/- 4.797 L x min(-1) (95% CI = -3.71, 1.22; p =
      0.301). Decline in maximum voluntary ventilation (MVV) in the COPD patients
      correlated with decreased FVC (r = 0.630) and increased RV (r = -0.546; p <
      0.05). Changes in spirometric variables for patients and controls did not explain
      significant variability in the arterial blood gas variables PaO2, PaCO2 or pH at
      altitude. CONCLUSIONS: We observed a decline in forced vital capacity in some
      COPD patients and normal subjects greater than expected for within day
      variability. Spirometric changes correlated with changes in reduced maximum
      voluntary ventilation in the patients but not with changes in resting arterial
      blood gases.

PMID- 9773901
TI  - Equivalent sensation curves of simultaneous lateral and vertical sinusoidal whole
      body vibration.
AB  - BACKGROUND: To evaluate the effects of whole body vibration on discomfort, the
      sensitivity to different frequencies as well as to different vibration axes must
      be regarded. This experimental study investigates the significance of lateral
      relative to vertical motions in the sensation of dual axis sinusoidal vibrations
      in sitting posture. The results are discussed in the context of the evaluation
      procedure proposed in the international standard ISO 2631 (13). METHODS: The
      experiments, in which 31 volunteers (16 female, 15 male, 19 51 yr) participated,
      used the method of adjustment. The subjects compared a single axis reference
      motion (aw = 1.25 ms(-2) rms) with a dual axis test motion of the same frequency.
      The magnitude of the test signal's component along the reference axis was kept
      constant at a fractional level of the reference magnitude (10, 25, 50, 75 or
      90%). The component perpendicular to the reference axis was adjusted by the
      subjects until the test signal was rated as being equally strong as the
      reference. Both vertical and lateral reference motions were applied. The
      frequencies used were 1.6, 3.15, 6.3 and 12.5 Hz. RESULTS: The shape of the
      resulting right-downwards bent equivalence curves was reasonably well fitted
      using the frequency weightings and evaluation procedure of ISO 2631. However,
      there were considerable quantitative discrepancies for frequencies above 1.6 Hz
      with an underestimation of the effects of lateral vibrations by a factor of 1.5
      2. Therefore, it is concluded that lateral vibrations above 1.6 Hz need more
      weight in the evaluation of discomfort caused by multi-axis whole body
      vibrations.

PMID- 9773902
TI  - Pilots with missing fingers and/or foot components: contemporary certification.
AB  - When an applicant with amputations presents to the Aviation Medical Examiner
      (AME) for Federal Aviation Administration (FAA) medical certification several
      potential "gates" must be passed. The first gate is the AME's impression of the
      applicant's reaction and adaptation to the loss. The second gate is the
      operational flight performance demonstration by the applicant, and/or, further
      clinical evaluation of the applicant's status, if necessary. Some applicants will
      pass gate one and become certified. Others may need to progress through the
      second gate. A few applicants will be unable to transit the gates and will not
      become certified.

PMID- 9773903
TI  - Case reports of insulin-dependent glider pilots in the United Kingdom.
AB  - BACKGROUND: Insulin-dependent diabetics have not been licensed to fly as pilots.
      In the United Kingdom, the standards for flying gliders solo were adopted from
      those required for driving licences, allowing diabetics to fly gliders. No
      accidents had been reported. HYPOTHESIS: My hypothesis was that insulin-dependent
      diabetics can fly as pilots without danger. METHOD: A survey was conducted among
      insulin-dependent glider pilots, using a questionnaire to determine their flying
      experience and establish any difficulties arising from their disease. RESULTS:
      Respondents reported that their blood sugar level could be managed in flight and
      that while complications of diabetes occurred, they had not presented a flight
      safety hazard. CONCLUSION: Insulin dependent diabetic pilots flying solo
      recreational aircraft are not at greater risk than when driving road vehicles.
      The decision by the British Gliding Association to allow insulin dependent pilots
      to fly gliders solo has been justified by experience.

PMID- 9773904
TI  - Case report: postconcussion syndrome after minor head injury.
AB  - A 31-yr-old flight medic struck the top of his head while loading a patient onto
      an ambulance. He sustained a momentary alteration of sensorium but otherwise
      seemed fine. Approximately 1 week after the incident, he experienced the onset of
      headaches and disabling vertigo that persisted over the next 2 mo, gradually
      decreasing in severity with time. Although not deemed significant at the time of
      injury, a mild head injury can result in postconcussion syndrome, a collection of
      neurologic symptoms that can persist for some time before resolving. This case
      emphasizes the need for a period of observation after head trauma before clearing
      aviators for flying duties.

PMID- 9773905
TI  - Compulsive sexual behaviors--difficult aeromedical disposition.
AB  - Axis I psychiatric disorders generally are considered incompatible with both the
      issuance and subsequent maintenance of aeromedical clearance certificates. Little
      doubt exists as to the impact that conditions such as anxiety disorders, mood
      disorders, or substance-related disorders have on the conduct of safe flight.
      Nevertheless, different compulsive sexual behaviors (CSBs), which now are thought
      to share similar origins and associated comorbidity, can similarly affect impulse
      control, judgment, concentration, and insight. Yet, these conditions frequently
      are handled administratively (if not legally). Moreover, in practice CSBs fall
      within a spectrum of behaviors from "normative" nonparaphilic sexuality to more
      deviant paraphilic behavior. Through the presentation of five selected cases seen
      at the Naval Operational Medicine Institute, this article explores examiner
      difficulty in establishing a diagnosis, discusses models useful in understanding
      the origins of these disorders, and highlights critical elements in establishing
      aeromedical disposition. The authors conclude that CSBs may be associated with
      anxiety, dysphoria, a pattern of increased risk taking, a high threshold for
      arousal, and poor judgment, which may impact the safety of flight. A
      comprehensive psychiatric evaluation is essential in determining aeromedical
      disposition, and consideration should be given to reviewing these cases from a
      medical perspective prior to any administrative disposition.

PMID- 9773906
TI  - Inflight medical kits.
AB  - Great controversy surrounds the issue of United States (US) air carrier inflight
      medical kits. Although there are four medications mandated by the Federal
      Aviation Administration (FAA) that appeared to be adequate as determined by a
      1988 survey, there is now a renewed call to review the medical kit contents with
      an eye toward making them more robust. This has been prompted by several well
      publicized inflight medical events and the fact that overseas airlines have a
      very wide array of pharmaceuticals and supplies. Consequently, the Aerospace
      Medical Association (AsMA) convened a Task Force of physicians across the major
      specialties to put forward recommendations regarding medication, medical
      supplies, and automatic external defibrillators (AEDs). These deliberations were
      based upon a survey of AsMA physician members.

PMID- 9773907
TI  - Pulmonary embolism in a pilot.

PMID- 9773908
TI  - You're the flight surgeon. Parathyroid adenoma with primary hyperparathyroidism,
      recurrent renal calculi, and brown tumor.

PMID- 9773909
TI  - Multicenter, open-label study of recombinant human DNase in cystic fibrosis
      patients with moderate lung disease. DNase International Study Group.
AB  - Cystic fibrosis is characterized by the accumulation of thick viscous purulent
      secretions. Recombinant human deoxyribonuclease I (rhDNase) breaks down
      extracellular DNA, which contributes to the increased viscosity of sputum. A
      multinational, open-label study was conducted in 974 cystic fibrosis patients
      with moderate lung disease [forced vital capacity (FVC) 40-70% of predicted
      values] to examine the safety and efficacy of aerosolized rhDNase, 2.5 mg, once
      daily over a period of at least 12 weeks. Patients were assessed under conditions
      reflecting routine clinical practice. During rhDNase therapy, at least one
      respiratory tract infection (RTI) requiring intravenous antibiotics was
      experienced by 29.5% of patients. Forced expiratory volume in 1 second (FEV1) and
      FVC were significantly improved from baseline by a mean of 10.5% and 7.2%,
      respectively. Voice alteration and pharyngitis were the most frequent rhDNase
      related adverse events, but only 2% of all patients discontinued treatment due to
      adverse events. The results obtained were similar to a subanalysis of data from
      the first 3 months of a placebo-controlled U.S. study. The patients in the
      present study had a similar frequency of RTIs and improvement in pulmonary
      function, and reported fewer rhDNase-related and cystic fibrosis-related adverse
      events than patients in the U.S. study. We conclude that administration of
      rhDNase is safe, well tolerated, and effective under conditions reflecting
      routine clinical practice in patients with cystic fibrosis and moderate lung
      disease.

PMID- 9773911
TI  - Inspiratory flow limitation in children with bronchopulmonary dysplasia.
AB  - The objective of this study was to compare pulmonary function tests of children
      with bronchopulmonary dysplasia (BPD) and asthma, and to evaluate children with
      BPD for evidence of upper airway obstruction. This is a case-control
      retrospective study of pulmonary function tests (PFTs) of 11 children with BPD
      between 5 and 8 years of age who were followed by pediatric pulmonologists, and
      of 32 age- and height-matched children with asthma. The median forced vital
      capacity (FVC), forced expiratory volume in one second (FEV1), and peak
      expiratory flow (PEF) were significantly lower in the BPD group (0.86 L, 0.79 L,
      120 L/min) than in the asthmatic group (1.34 L, 1.21 L, 155 L/min; P = 0.002, P =
      0.007, P = 0.004, respectively). Both groups were equally hyperinflated (median
      thoracic gas volume 155% of predicted values in the BPD compared to 152%
      predicted in the asthma group; P = 0.67), and both groups showed decreases in air
      trapping after a bronchodilator. The ratios of forced expiratory flow at 50% of
      the FVC to forced inspiratory flow at 50% of the FVC (FEF50%/FIF50%) and FEV1 to
      PEF (FEV1/PEF) were used to assess upper airway obstruction and were higher in
      children with BPD than asthma (P = 0.0001 and P = 0.035, respectively). We
      conclude that pulmonary function of children with BPD who are still symptomatic
      after 5 years of age is different from age-matched children with asthma, and the
      children with BPD demonstrate significant inspiratory flow limitations.

PMID- 9773910
TI  - Efficacy of corticosteroids in acute bronchiolitis: short-term and long-term
      follow-up.
AB  - Corticosteroids continue to be used by many physicians to treat infants with
      bronchiolitis. The aim of this study was to examine the short-term and long-term
      efficacy of oral corticosteroid therapy when added to beta2-agonists in infants
      with mild to moderate bronchiolitis (defined as the first episode of wheezing
      associated with low grade fever, rhinitis, tachypnea, and increased respiratory
      effort in a previously healthy infant during the winter months). Infants with
      mild to moderate bronchiolitis, were randomly assigned to receive either oral
      prednisone (2 mg/kg/day) or placebo for 3 days. All patients received nebulized
      albuterol q.i.d. during this period. Upon admission and after 3 days of therapy,
      a clinical score was assigned based on respiratory rate, use of accessory muscle,
      and the presence of wheeze. Oxygen saturation (SaO2) was also measured. On day 7,
      we inquired as to the well-being of each child. Two years later, the development
      of chronic respiratory symptoms was assessed. Thirty-eight infants were enrolled
      in the study; 20 received prednisone and 18 received placebo. Both groups were
      similar in terms of age, duration of illness prior to enrollment, pretrial
      medication use, clinical severity of bronchiolitis, history of atopy, and family
      history of atopy. After 3 and 7 days of treatment, both groups showed similar
      clinical improvement and there were no statistically significant differences
      between the two groups in the clinical score or in the SaO2. No major side
      effects were observed. Two years later, 32% of the infants continued to suffer
      from chronic respiratory symptoms, with a similar prevalence in both groups. We
      conclude that a 3-day course of oral corticosteroids is of no benefit to infants
      with mild to moderate bronchiolitis who are also treated with an inhaled beta2
      agonist.

PMID- 9773912
TI  - Tracheal aspirate surface tension in babies with hyaline membrane disease:
      effects of synthetic surfactant replacement.
AB  - Our objective was to determine changes in surface tension of tracheal aspirate
      over the first 4-5 days of life in babies with hyaline membrane disease, with and
      without synthetic surfactant replacement. Tracheal aspirates were collected prior
      to and for 96-108 hr after initiation of a randomized double-blind trial of
      synthetic surfactant (EXOSURF Neonatal) or air-treated control patients. Using
      the captive bubble technique, we measured minimum surface tension (initial
      adsorption, first quasi-static compression, dynamic cycling at 30 cpm, second
      quasi-static compression and 5 min after quasi-static compressions) in 39
      surfactant-treated and 44 control babies. We also compared minimum surface
      tension with the respiratory support provided. Twelve hours after one dose of
      synthetic surfactant, minimum surface tension on first quasistatic compression
      decreased significantly from 20.9+/-1.4 to 17.6+/-1.3 mN/m compared to air
      treated babies, who did not show any change. Reduction in minimum tracheal
      aspirate surface tension on first quasi-static compression and during dynamic
      cycling over 48-60 hr occurred more rapidly in surfactant-treated babies.
      Ventilator support did not correlate with minimum tracheal aspirate surface
      tension. We conclude that treatment of babies with synthetic surfactant improved
      tracheal aspirate minimum surface tension within 12 hr of the first dose and for
      the next 48-60 hr.

PMID- 9773913
TI  - Can a difference in chest wall mechanics explain the lower respiratory drive
      during propofol versus halothane anesthesia in children?
AB  - This article extends previous work which suggested that respiratory drive was
      lower during propofol compared with halothane anesthesia. The aim of this study
      was to assess simultaneously chest wall motion, measured with respiratory
      inductive plethysmography (RIP), and respiratory drive measured by P0.1 the
      pressure generated during the initial 100 msec of an occluded inspiratory effort.
      Ten healthy children age 3 to 6 years who presented for a dental restorative
      procedure that required in excess of 2.5 hours were recruited. Patients were
      anesthetized with propofol (2.5 mg x kg(-1); 15 mg x kg(-1) x hr) or halothane
      (1.25%), in a randomized crossover study design. Following induction of
      anesthesia, RIP bands were placed at the level of the nipples and the umbilicus
      for the measurement of rib cage and abdomen excursion, respectively. Flow and
      airway pressure were measured. A manually operated pneumatic balloon was used for
      brief airway occlusion. Following a 60-minute washin/out of the anesthetic, the
      children were removed from mechanical ventilation and spontaneous ventilation was
      reinstated. The RIP signals were calibrated by the method of simultaneous
      solution of equations. The phase lag was calculated. During airway occlusion the
      maximal excursion of the calibrated rib cage trace (RMAX) was measured; a
      negative value indicated retraction of the rib cage. Respiratory drive was
      assessed both at a fixed interval (100 msec) (P0.1) and fixed proportion (10%)
      (P10%) of the occluded inspiratory effort. Significance of differences were
      assessed with a paired t-test (P-value < 0.05). Thoracoabdominal asynchrony was
      greater during halothane than propofol anesthesia, as was the amount of rib cage
      retraction, evidenced by lower values of RMAX; respiratory drive was higher
      during halothane than propofol anesthesia, as evidenced by higher values of both
      P0.1, and P10%. We conclude that during halothane anesthesia altered chest wall
      mechanics may result in a greater respiratory drive than during propofol
      anesthesia.

PMID- 9773914
TI  - Hydatid disease in childhood: a retrospective analysis of 376 cases.
AB  - During a 20-year period, 376 children with hydatid disease were treated at
      Hacettepe University Ihsan Dogramaci Children's Hospital. There were 223 males
      and 153 females with a mean age of 8.9+/-0.1 years. Hydatid cysts were localized
      in the lungs in 222 patients, in the liver in 56 patients, and in other organs in
      the remaining patients. Cough, fever, and abdominal pain were the most common
      symptoms. One hundred eight patients had medical, 182 patients had surgical, 73
      patients had medical and surgical, and 4 patients had medical and percutaneous
      drainage treatment as the initial therapy. When evaluating the results of
      therapy, the relapse rate was higher in surgically treated patients than
      medically treated patients. We conclude that medical treatment of childhood
      hydatidosis is best, except in cases with complications such as infection,
      parenchymal compression or obstruction of airways, bile duct or viscera; all of
      these are indications for surgical therapy.

PMID- 9773915
TI  - Isovolume pressure/flow curves of rapid thoracoabdominal compressions in infants
      without respiratory disease.
AB  - To assess whether flow limitation can be achieved during rapid thoracoabdominal
      compressions (RTC), we performed esophageal pressure measurements in 11 healthy
      infants less than 3 months of age. Recordings of esophageal pressure were
      obtained with an esophageal balloon placed in the lower esophagus. RTCs were
      started at 20 cm H2O and increased to 140 cm H2O or until the infant responded
      with glottic closure to the compression. Flow limitation was assessed from
      isovolume pressure flow curves at peak flow and flow at FRC (V'max, FRC). The
      transmission of jacket pressure was higher at peak flow than at FRC for pressures
      below 60 cm H2O, due to active inspiration during the compression. Active
      inspiration was not observed at compression pressures above 80 cm H2O, as
      reflected by a plateau in the esophageal pressure tracing. Esophageal pressure
      increased parallel to the compression pressure at jacket pressures below 60 cm
      H2O. The relationship between jacket pressure and esophageal pressure became
      curvilinear at high compression pressures and plateaued at compressions above 100
      cm H2O, so that further increases in jacket pressure did not increase esophageal
      pressure. Flow limitation was seen in all infants studied, as indicated by a lack
      of increase in flow with increasing esophageal pressures for V'max, FRC. Jacket
      compression pressures of 60 cm H2O and esophageal pressures of 20 cm H2O were
      sufficient to reach maximal expiratory flow. These data indicate that jacket
      pressure is a poor indicator of pleural pressure at high compression pressures in
      young healthy infants, and high pressures are not needed, as flow limitation is
      seen during RTCs at moderate compression pressures.

PMID- 9773916
TI  - The lungs in congenital diaphragmatic hernia: do we understand?

PMID- 9773917
TI  - Neonatal screening for cystic fibrosis: it is time.

PMID- 9773919
TI  - Homozygous sickle cell disease and cystic fibrosis in an adolescent.

PMID- 9773918
TI  - Hypoxia and chest pain due to acute constipation: an underdiagnosed condition?
AB  - An obese, previously healthy, 10-year-old boy presented with acute respiratory
      distress, chest, and abdominal pain. He was hypoxic and dyspneic in the emergency
      room. The abdomen was distended and tender, and the rectum was full of hard
      stool. Following catharsis, he made a complete recovery with resolution of all
      clinical signs. A review of the literature reveals that acute constipation as a
      cause of hypoxia and respiratory distress has been recognized, but has rarely
      been reported. We believe that this is a common phenomenon but probably
      infrequently recognized.

PMID- 9773920
TI  - Synergistic effects of high-frequency ventilation and inhaled nitric oxide in the
      treatment of hypoxemic respiratory failure in infancy.

PMID- 9773921
TI  - Concerning CCAM in children.

PMID- 9773922
TI  - Evidence-based medicine.

PMID- 9773924
TI  - Roles of COX-1 and COX-2 in gastrointestinal pathophysiology.
AB  - In this review, COX-1 and COX-2 proteins have been shown to be homologous in
      protein structure and ability to synthesize PG, but they have been also shown to
      be induced differently. COX-1 mRNA and protein have been shown to be induced
      slowly in intestinal crypt cells in response to irradiation and suggested to be
      important for crypt cell survival. Therefore, the cox-1 gene is suggested to be a
      delayed response gene in some systems. However, in cox-1 gene knockout animals
      there are no pathological gastric and intestinal findings. Although the precise
      roles of COX-1 in epithelial proliferation and differentiation in the
      gastrointestinal tract are not yet known, it apparently acts as a constitutive PG
      producer, thereby protecting the mucosa. On the other hand, COX-2 mRNA and
      protein have been shown to be induced rapidly in inflammatory sites of the
      stomach and colon. Thus, COX-2-derived PG presumably plays a role in the repair
      process of gastritis, ulcers, and colitis. Furthermore, loss of apc gene function
      probably induces COX-2 mRNA in gastrointestinal mucosa. Thus, high expression
      levels of COX-2 may lead to phenotypic changes in both intestinal epithelial
      cells and colon cancer cells.

PMID- 9773923
TI  - Chemokine expression in Helicobacter pylori-infected gastric mucosa.
AB  - Inflammatory response to Helicobacter pylori is characterized by infiltration of
      neutrophils, monocytes, and lymphocytes into the gastric mucosa. Interleukin-8
      (IL-8), a prototype of the CXC-chemokine subfamily, may be a key modulator in
      inducing neutrophil migration and activation in H. pylori-infected gastric
      mucosa. IL-8 is produced by gastric epithelial cells in response to H. pylori
      infection, and IL-8 expression is induced by local production of proinflammatory
      cytokines and attachment of H. pylori organisms to the gastric epithelial cell
      surface. Multiple genes in the H. pylori cag pathogenicity island seem to be
      involved in inducing the epithelial IL-8 response to H. pylori attachment.
      Activation of the transcription factor, nuclear factor kappaB (NF-kappaB), is
      associated with this IL-8 response. Reactive oxygen intermediates whose
      production is increased in H. pylori-infected gastric mucosa may also modulate IL
      8 expression in the gastric mucosa. Recent reports also suggest that the local
      production of CC-chemokines, another chemokine subfamily, is important in H.
      pylori-associated gastritis.

PMID- 9773925
TI  - Enhanced mucosal expression of interleukin-6 mRNA but not of interleukin-8 mRNA
      at the margin of gastric ulcer in Helicobacter pylori-positive gastritis.
AB  - To elucidate the role of interleukin (IL)-6 and IL-8 in the pathogenesis of
      gastric ulcer in Helicobacter pylori-positive gastritis, in situ hybridization
      using digoxigenin-labeled cDNA probes for both cytokines was performed.
      Immunogold silver staining was added to further improve the sensitivity of this
      non-radioactive hybridization. The biopsy specimens were taken from eight
      patients with active gastric ulcer before treatment, in all of whom H. pylori was
      positive. Macrophages (the putative producers of these cytokines) were determined
      by immunohistochemistry using anti-CD68 monoclonal antibodies (KP-1). IL-6 mRNA
      was most abundantly expressed in the epithelium and in the infiltrating cells in
      tissue adjacent to gastric ulcer. Quantitative analysis disclosed a significant
      increase in cells positive for IL-6 mRNA near the ulcer margin compared to cells
      in the surrounding tissue. In contrast, cells positive for IL-8 mRNA were
      observed in equal proportions and evenly in the epithelium and over the entire
      layer of the gastric mucosa regardless of the presence of gastric ulcer. The
      majority of infiltrating cells positive for both IL-6 and IL-8 mRNA were thought
      to be macrophages because of their morphologic features and their
      immunohistochemical reactivity to CD68. These findings strongly suggest that IL-6
      is overexpressed at the margin of gastric ulcer in H. pylori-positive gastritis.

PMID- 9773926
TI  - Effect of pirenzepine on gastric endocrine cell kinetics during lansoprazole
      administration.
AB  - We studied the effect of pirenzepine on gastric secretion kinetics in rats in a
      hypochlorhydric state induced by lansoprazole, a proton pump inhibitor.
      Pirenzepine was administered intramuscularly at a dosage of 20 mg/kg twice daily;
      and lansorprazole, subcutaneously at 50 mg/kg once daily, both every day for 4
      weeks. After the 4-week treatment, serum gastrin and plasma somatostatin levels
      were determined by radioimmunoassay. In addition, gastrin cells, somatostatin
      cells, and enterochromaffin-like cells were immunostained and counted. Serum
      gastrin levels were elevated, and gastrin and enterochromaffin-like cell numbers
      increased in the group on lansoprazole alone, compared with these values in the
      control group (which received distilled water). In the group on the lansoprazole
      and pirenzepine combination, serum gastrin levels decreased, and gastrin and
      enterochromaffin-like cell numbers were significantly decreased, compared with
      the respective variables in the group on lansoprazole alone, while the number of
      somatostatin cells increased in the group on the combination. Plasma somatostatin
      levels did not vary significantly in any group. It was thus demonstrated that
      pirenzepine corrects the abnormal gastric secretion kinetics resulting from
      treatment with lansoprazole alone, such as hypergastrinemia and gastrin and
      enterochromaffin-like cell hyperplasia.

PMID- 9773927
TI  - A new quadruple therapy for the eradication of Helicobacter pylori. Effect of
      pretreatment with omeprazole on the cure rate.
AB  - To elucidate whether pretreatment with omeprazole decreases the cure rate of
      Helicobacter pylori infection with a new quadruple therapy, and thus, whether
      this pretreatment should not be used in clinical practice, we conducted a
      randomized trial. Ninety patients with chronic peptic ulcer disease and nonulcer
      dyspepsia, with biopsy-proven H. pylori infection were randomly assigned to the
      two following regimens: Group 1 (n = 45) received omeprazole 20 mg once daily for
      2 weeks (days 1-14), and 500 mg amoxicillin granules and 250 mg metronidazole
      thrice daily, and roxithromycin 150 mg twice daily for 1 week (days 8-14), Group
      2 (n = 45) received the same antibiotic treatment as group 1 for 1 week (days 1
      7), in addition to omeprazole treatment for 2 weeks (days 1-14). Four weeks after
      the treatment ended, endoscopy was repeated, with two biopsy specimens each taken
      from the antrum and the corpus (total of four specimens) for a urease test,
      histological analysis, and culture to establish cure of infection. A patient was
      regarded as cured only if all three methods gave negative results for H. pylori.
      In the intention-to-treat analysis, 42 of 45 patients (93.3%; 95% confidence
      intervals [CI], 81.7%-98.6%) in group 1 were cured compared with 43 of 45
      patients (95.6%; 95% CI, 84.9%-99.5%) in group 2. In the per-protocol analysis,
      the corresponding figures were 42/44 (95.5%; 95% CI 84.5%-99.4%) and 43/44
      (97.7%; 95% CI, 88.0%-99.9%). There were no significant differences in the cure
      rate between the two groups on either analysis. All patients, except for one who
      had an allergic reaction, completed the treatment regimens. Fifty to sixty
      percent of the patients had no side effects while the rest had mild to moderate
      side effects. The new quadruple therapy consisting of omeprazole, amoxicillin,
      metronidazole, and roxithromycin appears suitable for use in clinical practice,
      as the cure rate was 95% and no severe side effects were observed. Pretreatment
      with omeprazole did not reduce the cure rate for this new quadruple therapy.

PMID- 9773928
TI  - Glutathione depletion inhibits oxidant-induced activation of nuclear factor-kappa
      B, AP-1, and c-Jun/ATF-2 in cultured guinea-pig gastric epithelial cells.
AB  - The aim of this study was to reveal the role of intracellular glutathione in the
      oxidative stress responses of gastric epithelial cells. Metabolic radiolabeling
      with L-[35S]methionine and analysis of synthesized proteins by gel
      electrophoresis and fluorography showed that upon exposure to hydrogen peroxide
      (H2O2) or diamide, primary cultures of guinea-pig gastric epithelial cells
      rapidly induced several undefined proteins, as well as heat shock proteins. When
      intracellular glutathione was depleted to less than 10% of the control value by
      treatment with buthionine-[S,R]-sulfoximine, these inductions were completely
      inhibited. Gel mobility shift assay demonstrated that H2O2 and diamide rapidly
      activated nuclear factor-kappa B (NF-kappaB), and diamide activated activator
      protein (AP)-1, and c-Jun/activating transcription factor (ATF)-2, suggesting
      that the response may be coupled to these reduction-oxidation (redox)-sensitive
      transcription factors, as well as heat shock transcription factor 1. The
      activations of NF-kappaB, AP-1, and c-Jun/ATF-2 by the oxidants did not occur in
      glutathione-depleted cells. Northern blot analysis showed that glutathione
      depletion markedly or completely suppressed the diamide-induced expression of c
      fos and c-jun mRNAs. These results suggest that intracellular glutathione redox
      may participate in the initiation of oxidative stress responses; thereby, it
      plays an important role in gastric mucosal defense.

PMID- 9773929
TI  - Effect of trans-retinoic acid and folic acid on apoptosis in human gastric cancer
      cell lines MKN-45 and MKN-28.
AB  - Induction of apoptosis has been implicated as an anticarcinogenic mechanism of
      both folic acid and retinoic acid. The ability of retinoic acid or folic acid to
      induce gastric cancer cell apoptosis was investigated in the human gastric cancer
      cell lines MKN-45 and MKN-28, and DNA fragmentation was studied in situ by
      terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling and
      DNA agarose gel electrophoresis. The rates of apoptosis in both the poorly
      differentiated MKN-45 and the well differentiated MKN-28 cell line were less than
      5% after treatment with either retinoic or folic acid. Apoptosis may be induced
      by the administration of retinoic acid or folic acid, and the apoptosis indices
      of MKN-45 and MKN-28 cells were related to the doses of these drugs. The
      induction of gastric cancer cell apoptosis may play a role in the
      anticarcinogenic effect of retinoic acid and folic acid, both of which are
      potential agents for the treatment of human gastric cancer.

PMID- 9773930
TI  - Advantages of immunostaining over DNA analysis using PCR amplification to detect
      p53 abnormality in long-term formalin-fixed tissues of human colorectal
      carcinomas.
AB  - To study the appropriate period for formalin fixation in order to detect p53
      abnormalities in formalin-fixed tissue, we used seven surgically resected human
      colorectal cancer specimens. The immunohistochemical reactivity of p53
      immunostaining and amplification of DNA by polymerase chain reaction (PCR) of the
      p53 gene were compared after various periods of 10% formalin fixation (1 day, and
      1, 2, 4, and 8 weeks). For comparative immunostaining, we used the monoclonal
      antibody Ki-67 (MIB-1), and for comparative polymerase chain reaction (PCR), K
      ras at codon 12 was amplified. Immunostaining was performed by the streptavidin
      biotin method with microwave retrieval, and PCR amplifications were performed by
      the nested PCR method. p53 and Ki-67 immunoreactivity did not change essentially
      for up to 2 weeks and 1 week, respectively, of formalin fixation. PCR
      amplification for p53 at exon 8 and K-ras at codon 12 was successful until 1 day
      and 2 weeks, respectively, of formalin-fixation for the specimens of all seven
      cases. Thereafter, the amplification tended to worsen as the fixation time
      lengthened. Further, the DNA was more successfully amplified in the second PCR
      than in the first. These results suggest that to detect p53 abnormality in
      specimens that have been formalin-fixed for long periods, immunohistochemical
      staining may have advantages over DNA analysis with PCR amplification.

PMID- 9773932
TI  - Blood digestion-induced splanchnic hyperemia and portal blood flow in portal
      hypertensive rats and the role of octreotide.
AB  - We aimed to investigate whether the presence of blood within the intestinal lumen
      after variceal bleeding would lead to reactive intestinal hyperemia, which in
      turn could result in the worsening of portal hemodynamics, and thus bleeding
      recurrence. Two models of portal hypertensive Wistar rats were used: 32 CCl4
      cirrhotics with a low index of portal-systemic shunting and 32 that had been
      previously subjected to portal vein stenosis, with a high index of portal
      systemic shunting; 32 Wistar rats served as controls. The rats were divided into
      four groups, each comprising 8 cirrhotics, 8 portal vein stenosis rats, and 8
      controls. Intestinal microcirculation and portal blood flow were assessed by
      laser-Doppler and transit-time ultrasonic flow probes, respectively, before and
      60 min after the injection of 2 ml of blood (groups 1 and 2) or an equal volume
      of NaCl 0.9% (placebo; groups 3 and 4) into the intestinal lumen. Octreotide (0.2
      microg/100 g body weight [BW]) (groups 1 and 3) or NaCl 0.9% (groups 2 and 4) was
      then given subcutaneously, and 30 min later the final measurements were
      performed. The presence of blood within the intestinal lumen resulted in an
      increase in intestinal microcirculation in rats in all groups, while portal blood
      flow was increased in portal vein stenosis rats and controls, and decreased in
      cirrhotics. The presence of NaCl 0.9% had no effect. Octreotide, but not NaCl
      0.9%, led to a decrease in both intestinal microcirculation and portal blood
      flow. The findings of this study suggest that intestinal hyperemia induced by
      digestion of blood in the enteric lumen increases or decreases portal blood flow,
      the result being strongly related to the portal hypertension model used. Since
      the main difference between the models was the extent of portal-systemic
      shunting, this may suggest a relationship between portal blood flow and portal
      systemic shunting. This relationship could explain why variceal bleeding stops in
      some patients but recurs in others.

PMID- 9773931
TI  - Importance of cytogenetic markers for multiple primary carcinomas in colorectal
      cancer: chromosome 17 and p53 locus translocation.
AB  - The incidence of non-familial multiple primary cancer in colorectal cancer
      patients has increased in recent years in Japan. To clarify the characteristic
      genetic aberrations in such multiple cancers, we examined structural chromosomal
      aberrations by fluorescence in situ hybridization, using chromosome 17-specific
      and p53 cosmid DNA probes. We established short-term cultures of 78 surgical
      specimens and were able to obtain observable metaphase spreads in 23 single
      colorectal cancer specimens and in 6 colorectal cancer specimens from patients
      with double primary cancers. The frequency of chromosome 17 and/or p53 locus
      translocation was significantly greater in tumors with double cancer than in
      single colorectal cancers (P < 0.05 and P < 0.01, respectively). These
      aberrations in double cancers frequently appeared even at an early Dukes' stage
      (A and B) of colorectal carcinoma. Our results suggest that translocation of
      chromosome 17 and the p53 locus may be specific genetic events probably
      associated with carcinogenesis of multiple primary cancers in colorectal cancer.

PMID- 9773933
TI  - Relationship between interferon therapy and variability in nonstructural gene 5b
      of hepatitis C virus.
AB  - The hepatitis C virus (HCV) quasispecies nature in the hypervariable region (HVR)
      has been reported and found to relate to the effectiveness of interferon (IFN)
      treatment. However, the quasispecies nature in the nonstructural (NS) 5b region
      remains to be addressed. To examine this characterization and relationship with
      IFN therapy, we sequenced six independent HCV clones from each of eight patients.
      The eight patients were classified as responders or nonresponders to IFN. In the
      four responders, we found one to three isolates in each of the six clones. In the
      nonresponders, the six clones consisted of four, five, six, and six isolates,
      respectively. Compared the (NS) 5b genes of the isolates obtained from the
      patients with that of the reported hepatitis C virus HC-C2 or HC-J6 isolate the
      ratio of nonsynonymous to total substitutions ranged from 17.61% to 30.95% in the
      responders and from 33.11% to 76.47% in the nonresponders. We also compared
      posttreatment with pretreatment sequences. The average number of varying amino
      acids ranged from 5.5 to 9.0 in isolates remaining after IFN treatment and from
      4.3 to 5.5 in the isolates that disappeared with IFN treatment. Two changed amino
      acids (glycine to arginine and valine to isoleucine) (compared with the
      pretreatment clones) were found in the posttreatment clones of one of the
      responders and one amino acid change (valine to alanine) was found in another
      responder. These results suggest that the NS5b quasispecies correlates with IFN
      treatment effectiveness. These results also implied that the heterogeneity in
      different hierarchical strata has a common impact on IFN treatment, making
      infected patients resistant to IFN. Our study also provides evidence that HCV
      elimination and mutation may occur simultaneously during IFN therapy.

PMID- 9773934
TI  - Analysis of peripheral blood mononuclear cell stimulated with pyruvate
      dehydrogenase complex, T-cell receptors from patients with primary biliary
      cirrhosis.
AB  - Progressive destruction of the intrahepatic bile ducts in patients with primary
      biliary cirrhosis (PBC) is thought to be mediated by cytotoxic T cells which
      recognize certain epitopes, such as the pyruvate dehydrogenase complex (PDC). To
      clarify the T-cell repertoire in PBC, we analyzed T-cell receptor (TCR) Vbeta
      chain messages expressed in peripheral blood mononuclear cells (PBMCs) stimulated
      with PDC and in liver biopsy specimens. PBMCs from 12 PBC patients and 6 healthy
      controls were examined. The TCR Vbeta repertoires of unstimulated PBMCs and PBMCs
      stimulated with PDC purified from bovine heart were analyzed, using the reverse
      transcriptase-polymerase chain reaction (RT-PCR) and single-strand conformation
      polymorphism (SSCP). Liver biopsy specimens from 5 PBC patients were also
      analyzed. In the PBC patients, several different T-cell clones, some of which
      showed the same mobility, were evident in both the PDC-stimulated and
      unstimulated PBMCs, as demonstrated by SSCP analysis. In addition, TCR clonality
      of infiltrating lymphocytes in the liver was also observed in PBC patients,
      showing common clonal T-cell accumulation with that seen in PBMCs stimulated with
      PDC. These data indicate that common clonal T-cell accumulation specific for PDC
      may be present in both peripheral PBMCs and the liver of patients with PBC.

PMID- 9773935
TI  - Defects of cholecystokinin (CCK)-A receptor gene expression and CCK-A receptor
      mediated biological functions in Otsuka Long-Evans Tokushima Fatty (OLETF) rats.
AB  - Recent studies in genetically obese and diabetic Otsuka Long-Evans Tokushima
      Fatty (OLETF) rats suggest defects of cholecystokinin (CCK)-A receptor gene
      expression and CCK-A receptor-mediated biological functions such as pancreatic
      juice, protein, and gastric acid secretion. The present studies were undertaken
      to further examine CCK-A receptor gene expression and CCK-A receptor-mediated
      biological functions in the pancreas, stomach, and brain of OLETF rats.
      Expression of the CCK-A receptor gene could not be detected in the stomach,
      pancreas and brain by the reverse-transcription polymerase chain reaction (RT
      PCR) method and Southern blotting of the PCR products. Southern blot analysis of
      genomic DNA from OLETF and control Long-Evans Tokushima Otsuka (LETO) rats with
      CCK-A receptor fragment as a probe revealed different restriction bands.
      Expression of the CCK-B receptor gene was observed in the stomach, pancreas, and
      brain in both OLETF and LETO rats by the RT-PCR method, with expression of the
      CCK-B receptor gene markedly enhanced in OLETF rats compared with that in LETO
      rats. Consistent with the defect of CCK-A receptor gene expression, CCK-A
      receptor-mediated biological functions were not observed in these organs.
      Perfused exocrine and endocrine pancreas of OLETF rats were insensitive to CCK
      stimulation but not to carbamylcholine stimulation. Basal gastric acid and
      pepsinogen secretions in OLETF rats were higher than in LETO rats. OLETF rats
      showed a significantly higher average daily food intake, gained body weight
      faster, and were heavier than LETO rats. The present study confirmed that OLETF
      rats have CCK-A receptor gene anomalies and demonstrated deficient CCK-A receptor
      mediated biological function in the pancreas, stomach, and brain.

PMID- 9773936
TI  - Primary gastric Burkitt's lymphoma presenting with c-myc gene rearrangement.
AB  - A 54-year-old man with primary gastric Burkitt's lymphoma is described. He was
      evaluated for appetite loss and intermittent midepigastric pain. Upper
      gastroduodenal endoscopy detected an ulcer in the lesser curvature of the body,
      and biopsy specimens revealed infiltration of medium-sized lymphoblasts with
      "starry sky" macrophages. The infiltrated cells were positive for a B-cell
      marker. Abdominal computed tomography scan demonstrated marked enlargement of the
      gastric wall, but no enlargement of lymph nodes. These findings led us to
      diagnose primary gastric Burkitt's lymphoma. The patient responded dramatically
      to CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)
      chemotherapy, but 6 months after his initial admission, the disease recurred in
      the stomach and bone marrow. Lymphoblastic cells were positive for B-cell markers
      (CD 10, 19, 20, and human leukocyte antigen [HLA]-DR) and showed an abnormal
      karyotype, 47, XY, t(8;14)(q24;q32), +12. In these cells, the Epstein-Barr virus
      genome was detected by polymerase chain reaction. Southern blot analysis revealed
      rearrangement of Ig heavy and light chain genes. In addition, c-myc gene
      rearrangement was detected. Eight months after the beginning of chemotherapy, the
      patient died of central nervous system involvement. To our knowledge, this is the
      first description of a genetic analysis of primary gastric Burkitt's lymphoma.

PMID- 9773937
TI  - Gastric lipoma presenting as upper gastrointestinal obstruction.
AB  - A 61-year-old man presented with an upper gastrointestinal obstruction caused by
      a submucosal gastric lipoma in the prepyloric area. The diagnosis was made
      coincidentally during his admission for another disease. Gastric resection was
      performed because of a large lipoma combined with florid gastric ulcers. The
      frequency of gastric lipoma, its differential diagnosis, means of diagnosis, and
      treatment are discussed.

PMID- 9773938
TI  - Unusual gastric polyp showing submucosal proliferation of glands: case report and
      literature review.
AB  - We report an unusual pedunculated polyp in the stomach in a 41-year-old woman.
      She was hospitalized because of epigastric discomfort. Endoscopy revealed a polyp
      with a long stalk in the fundus of the stomach. The polypectomyzed polyp measured
      23 x 18 x 9 mm and was characterized by submucosal proliferation of glands and
      cystic dilatation. The surface of the polyp was covered with gastric mucosa of
      fundic or pyloric gland type. The glandular structures consisted of various types
      of lining cells, including pyloric or mucous-neck cell type, surface mucous
      (foveolar) cell type, parietal-like cells, and somatostatin-positive cells. The
      submucosal glandular or cystic elements were connected with the overlying gastric
      mucosa through a defect of the muscularis mucosa, suggesting that this polyp may
      have been formed by the heterotopic inverted downgrowth of mucous glands into the
      submucosa. We discuss the histogenesis of this rare polyp and present a review of
      the literature.

PMID- 9773939
TI  - Aggressive non-Hodgkin's lymphoma after successful eradication of Helicobacter
      pylori and regression of gastric lymphoma of mucosa-associated lymphoid tissue.
AB  - A 57-year-old woman presented to our clinic with low-grade gastric lymphoma of
      mucosa-associated lymphoid tissue (stage IE) and Helicobacter pylori infection.
      She received a 2-week course of omeprazole and clarithromycin, resulting in
      eradication of H. pylori and histological disappearance of the lymphoma. However,
      9 months later (May 1996), multiple mass lesions were found around the pancreas
      and hepato-duodenal ligament on abdominal computed tomography. Inguinal lymph
      node biopsy revealed aggressive nodal type B-cell non-Hodgkin's lymphoma, diffuse
      large cell type. She received chemotherapy with cyclophosphamide, adriamycin,
      vincristine, and prednisolone, but failed to achieve remission and died in
      December 1996. There was no evidence of recurrent gastric lymphoma. This case
      emphasizes the importance of performing follow-up examinations to detect other
      neoplasms in patients with gastric lymphoma of mucosa-associated lymphoid tissue.

PMID- 9773940
TI  - Duodenal gastrinoma--clinical features and usefulness of selective arterial
      secretin injection test.
AB  - Duodenal gastrinoma is recognized as a relatively common cause of Zollinger
      Ellison syndrome, but its clinical and biological features are not well known.
      Here we report a case of duodenal gastrinoma with lymph node metastasis which was
      confirmed by pathology examinations. Hypergastrinemia and gastric acid
      hypersecretion were documented, but the secretin test showed negative results. An
      enlarged peripancreatic lymph node lying close to the pancreas head was the only
      positive finding on preoperative imaging studies. The results of the selective
      arterial secretin injection (SASI) test suggested that the primary tumor was
      located in the gastrinoma triangle. Finally, surgical exploration was carried out
      and a submucosal tumor, approximately 15 mm in size, was detected by
      intraoperative palpation at the posterior wall of the proximal portion of the
      duodenum. Intraoperative pathology examination demonstrated metastases to
      regional lymph nodes. The present case calls attention to the unique features of
      duodenal gastrinomas, which differ from those of pancreatic origin: a highly
      malignant potential for its small size, and submucosal location in the proximal
      duodenum. The SASI test is recommended for assessing the location of a primary
      lesion if it cannot be identified by various conventional imaging studies.

PMID- 9773941
TI  - Unusual variant of left paraduodenal hernia herniated into the mesocolic fossa
      leading to jejunal strangulation.
AB  - Paraduodenal hernia is a rare condition in which the small bowel loops are
      herniated into an unusual fossa in the periduodenal area. We treated a patient
      with paraduodenal hernia diagnosed preoperatively. A 28-year-old woman was
      admitted to our hospital because of intermittent abdominal pain. Abdominal
      ultrasonography revealed a large tumor adjacent to the pancreas. Provisional
      diagnosis made according to computed tomography (CT) findings was tumor of the
      pancreas tail. However, on a CT scan performed after the administration of
      diatrizoate meglumine/diatrizoate sodium (Gastrografin, Schering, Berlin,
      Germany) the mass was shown as a jejunum loop located between the stomach and the
      pancreas body. Subsequent laparotomy revealed that the jejunum loop was herniated
      into an unusually large mesocolic fossa and that the hernial orifice was covered
      by the adhesion between the transverse and descending colons. It seemed that the
      small intestine within the mesocolic fossa was strangulated by this adhesion. The
      patient's abdominal pain resolved postoperatively. These observations suggest
      that paraduodenal hernia should be suspected in patients with chronic, atypical
      abdominal pain, regardless of the findings for small bowel obstruction.

PMID- 9773942
TI  - Pyloric stenosis due to Crohn's disease.
AB  - Gastroduodenal involvement by Crohn's disease is relatively rare and occasionally
      causes pyloric stenosis, for which medical therapy may be ineffective and surgery
      may be required. We report on a 44-year-old man patient in whom corticosteroids
      had a marked effect in reducing pyloric stenosis caused by Crohn's disease. A
      proton-pump inhibitor was not effective, and Helicobacter pylori was negative.

PMID- 9773943
TI  - Rectal carcinoid tumor associated with the Peutz-Jeghers syndrome.
AB  - A 16-year-old man who had been diagnosed with the Peutz-Jeghers syndrome at the
      age of 8 years presented with crampy abdominal pain. Thorough examinations
      revealed a large jejunal polyp causing intussusception, as well as multiple
      polyps in the small and large intestines. Preoperative proctoscopy demonstrated
      the coexistence of a submucosal tumor in the rectum. Proctoscopic mucosal
      resection was performed and histological and immunohistochemical examinations led
      to a diagnosis of carcinoid tumor. Additional transanal resection of the rectal
      wall showed no residual tumor and the patient has been well for 2 years to date.
      Although malignant tumors are increasingly reported in association with the Peutz
      Jeghers syndrome, to our knowledge, there have been no previous reports of such
      an association in the English-language and Japanese literature.

PMID- 9773944
TI  - Propylthiouracil-induced severe hepatitis: a case report and review of the
      literature.
AB  - A 21-year-old woman was diagnosed as having Graves' disease in April, 1995.
      Thiamazole was administered; about a month later the patient had a skin rash and
      propylthiouracil (PTU) was given instead. Two months after commencing PTU, she
      rapidly developed jaundice, accompanied by severe liver damage. The drug-induced
      lymphocyte stimulating test was positive for PTU and she was diagnosed as having
      severe hepatitis induced by PTU. After pulse therapy with 500 mg of
      methylprednisolone was given for 3 days, liver function test results were
      gradually improved, and became normalized 1 1/2 months after admission. The
      pathology findings of the liver biopsy sample taken before administration of
      corticosteroid showed necrosis of hepatocytes predominantly around the central
      veins (i.e., zone 3 necrosis), and moderate to severe infiltration of lymphocytes
      and neutrophils in portal areas and lobules. Severe hepatic damage due to PTU is
      rare; 25 cases have been reported so far in the English-language literature. When
      we use PTU for patients with hyperthyroidism, we should keep in mind that severe
      liver damage induced by PTU can be fatal, and we should therefore diagnose it
      earlier by liver biopsy and lymphocyte stimulating test.

PMID- 9773945
TI  - Activated hepatic stellate cells participate in liver fibrosis in a patient with
      transfusional iron overload.
AB  - We describe liver fibrosis caused by iron overload after a long history of blood
      transfusion in a patient with chronic renal failure. Pertinent laboratory data
      were: serum (s)-Fe 148 microg/dl; unsaturated iron binding capacity (UIBC) 14
      microg/dl; s-ferritin 9350 ng/ml; human leukocyte antigen (HLA) A2, A24, B39,
      B55, Cw1, Cw7. Computed tomography revealed a high density in the liver, and
      laparoscopy revealed a brown liver. Liver histology showed bridging fibrosis from
      portal tracts. A heavy iron deposit was seen in Kupffer cells as well as in
      hepatocytes surrounded by fibrosis around the portal tracts. Immunocytochemistry
      revealed alpha-smooth muscle actin in many stellate cells distributed along the
      fibrotic area, and electron microscopy revealed infiltrating myofibroblastic
      stellate cells coexisting with collagen fibers around degenerated hepatocytes
      containing iron deposits. The findings are consistent with the notion that
      stellate cells play an important role in liver fibrogenesis in both genetic and
      transfusional iron overload hemochromatosis.

PMID- 9773946
TI  - Nine-year survivor after resection of cholangiocellular carcinoma with tumor
      thrombi in the main portal trunk.
AB  - We report a patient with cholangiocellular carcinoma with tumor thrombi in the
      main portal trunk who has survived for 9.5 years after hepatic resection. A 57
      year-old woman underwent an extended left lobectomy, and resection of the caudate
      lobe plus the main portal trunk for a liver tumor that had a portal tumor
      thrombus in the main portal trunk. The portal vein was reconstructed with an
      autologous vein graft obtained from the external iliac vein. Histological
      examination of the resected specimen revealed moderately differentiated tubular
      adenocarcinoma compatible with cholangiocellular carcinoma. Factors contributing
      to the patient's long-term survival are discussed. Aggressive surgical resection
      can be effective even for such an advanced case of cholangiocellular carcinoma.

PMID- 9773947
TI  - Acinar cell carcinoma of the pancreas associated with hypoglycemia: involvement
      of "big" insulin-like growth factor-II.
AB  - Apart from insulinomas, pancreatic tumors are rarely complicated by hypoglycemia
      and some may produce insulin-like growth factor II (IGF-II). To our knowledge,
      IGF-II-producing pancreatic tumors associated with hypoglycemia have not been
      reported previously. We describe what we believe to be the first case of "big"
      IGF-II-producing pancreatic acinar cell carcinoma. A 68-year-old man presented
      with a history of recurrent hypoglycemia. Abdominal computed tomography scan and
      magnetic resonance imaging showed a mass, approximately 5 cm in diameter, in the
      tail of the pancreas and two low-density areas in the liver. Low serum glucose
      was associated with low insulin levels and high levels of hormones (i.e.,
      glucagon and IGF-II) that are functionally opposite to insulin. Although serum
      IGF-II level was within the normal range, most IGF-II was of the high molecular
      weight form, as determined by Western immunoblot analysis. Based on these
      findings, a diagnosis of hypoglycemia induced by IGF-II-producing pancreatic
      tumor was made. Surgery was not possible because of the patient's poor general
      condition. The patient ultimately died as a result of malignant cachexia. At
      autopsy, a yellowish-white tumor was found in the tail of the pancreas, and a
      histopathologic diagnosis of acinar cell carcinoma was made.
      Immunohistologically, the tumor cells contained IGF-II in an irregular staining
      pattern, suggesting that the hypoglycemia was caused by a pancreatic tumor
      producing "big" IGF-II.

PMID- 9773948
TI  - Chronic asymptomatic pseudocyst with sludge aggregates masquerading as mucinous
      cystic neoplasm of the pancreas.
AB  - Pseudocyst of the pancreas is sometimes difficult to distinguish from mucinous
      cystic neoplasm of the pancreas. A 37-year-old asymptomatic Japanese man was
      diagnosed with hypertension. He had a 20-years history of habitual drinking of
      alcohol, but no history of pancreatitis or abdominal trauma. During examinations
      to ascertain the cause of hypertension, ultrasonography and computed tomography
      incidentally demonstrated a huge cyst in the head of the pancreas. Laboratory
      data were within normal limits, including serum levels of amylase,
      carcinoembryonic antigen, and carbohydrate antigen 19-9. Imaging studies showed a
      huge unilocular cyst, measuring 7 cm, in the head-to-body of the pancreas, and
      two small unilocular cysts, measuring 1.4 and 1.5 cm, in the tail and head of the
      pancreas, respectively. A mural nodule was suspected in the largest cyst.
      Endoscopic retrograde cholangiopancreatography demonstrated communication of the
      main pancreatic duct with the two small cysts in the head and tail of the
      pancreas but not with the huge cyst. There were no ductal changes suggesting
      chronic pancreatitis. Laparotomy was performed under the tentative diagnosis of
      potentially malignant mucinous cystic neoplasms of the pancreas. However,
      inflammatory adhesion was dense around the pancreas and the mural nodule
      suspected preoperatively was found to be sludge aggregates in a pseudocyst. The
      diagnosis of an intraoperative frozen section of the cyst wall was pseudocyst of
      the pancreas. Cystojejunostomy was performed. We report this case because the
      preoperative diagnosis was mucinous cystic neoplasm of the pancreas, but the
      diagnosis changed with careful intraoperative examinations, to pseudocyst of the
      pancreas. We discuss the differential diagnosis of the two conditions.

PMID- 9773949
TI  - A large inflammatory polyp of the gallbladder masquerading as gallbladder
      carcinoma.
AB  - An inflammatory polyp of the gallbladder is a rare variant of benign gallbladder
      polyp. Differentiation between an inflammatory polyp and polypoid gallbladder
      carcinoma is difficult when the polyp is more than 1 cm in diameter. We report a
      rare case of a large inflammatory polyp of the gallbladder masquerading as
      gallbladder carcinoma in a 37-year-old Japanese woman who was incidentally
      diagnosed with a large gallbladder polyp, measuring 1 cm in diameter, by
      ultrasonography. She was asymptomatic and physical examination was unremarkable.
      Abdominal ultrasonography and endoscopic ultrasonography revealed three polypoid
      lesions in the gallbladder. One lesion was an isoechoic polyp, measuring 15 x 8
      mm, showing a nodular surface and located in the fundus of the gallbladder. The
      other two lesions were hyperechoic polyps, measuring 5 x 5 mm, in the body of the
      gallbladder. Computed tomography and magnetic resonance imaging revealed marked
      enhancement of the largest polypoid lesion by dynamic study, and no lymph node
      enlargement was noted. Endoscopic retrograde cholangiography revealed a 12 x 8 mm
      polyp with an irregular surface in the fundus of the gallbladder. Superselective
      angiography of the cystic artery revealed neovascularity and a tumor stain in the
      fundus of the gallbladder. Cholecystectomy with lymph node dissection was
      performed. Intraoperative frozen section diagnosis of the largest polyp was an
      inflammatory polyp of the gallbladder. The other two polyps were cholesterol
      polyps. Inflammatory polyp should be considered as a differential diagnosis of
      hypervascular gallbladder polyps that measure more than 1 cm in diameter.

PMID- 9773950
TI  - Oxidative stress, glutathione and transcription factors. How are they related to
      gastric mucosal injuries?

PMID- 9773951
TI  - Genetic diagnosis: a troublesome method?

PMID- 9773952
TI  - A step to clarify the real target autoantigen in primary biliary cirrhosis.

PMID- 9773953
TI  - Molecular and cytogenetic diagnosis of lymphoproliferative disorders of the
      gastrointestinal tract.

PMID- 9773954
TI  - Comparison of PCR, (1-->3)-beta-D-glucan and galactomannan assays in sera of rats
      with experimental invasive aspergillosis.
AB  - We compared PCR, galactomannan detection assay using a latex agglutination test
      and (1-->3)-beta-D-glucan detection assay in detecting infection in rats
      experimentally infected with Aspergillus fumigatus. On day 2 after inoculation,
      (1-->3)-beta-D-glucan and nested PCR were positive for 80%, while galactomannan
      detection assay was positive for 60%. In addition, the positive result of nested
      PCR (87.5%) was higher than those of galactomannan detection assay (75%) and (1-
      >3)-beta-D-glucan (71.4%) on day 3 after inoculation. The sensitivity of nested
      PCR was superior to those of galactomannan detection assay and (1-->3)-beta-D
      glucan detection assay. The three diagnostic tests were compared with
      histopathological findings, and the sensitivity of three diagnostic tests was
      correlated with histopathological changes. In addition, the elevated levels of (1
      ->3)-beta-D-glucan paralleled the development and progression of pulmonary
      aspergillosis. Our results indicate that a combination of two or three of these
      tests seems to provide a rapid diagnosis of invasive aspergillosis and assist in
      the evaluation of the development and severity of invasive aspergillosis.

PMID- 9773955
TI  - An enzyme-linked immunosorbent assay and reference ranges for bisphosphoglycerate
      mutase in human erythrocytes.
AB  - We established an enzyme-linked immunosorbent assay (ELISA) system for the
      determination of human bisphosphoglycerate mutase (BPGM) protein content in human
      erythrocytes using a polyclonal anti-BPGM antibody, we determined reference
      ranges for BPGM protein content, synthase activity, and specific activity in
      human erythrocytes. We produced a recombinant human BPGM (rBPGM) by gene
      manipulation using E. coli and then obtained the polyclonal antibody by
      immunizing rabbits with purified rBPGM. The reproducibility of the ELISA was in
      an acceptable range with a coefficient of variation under 1.5%. The ELISA was
      reliable in the range of 0.1 to 10 ng/mL. The polyclonal anti-rBPGM antibody did
      not show any cross-reaction with recombinant human B type phosphoglycerate
      mutase, which is highly homologous to rBPGM. The ELISA was found to be practical
      for the determination of BPGM protein content in human erythrocytes. The mean
      BPGM protein content was 56.3+/-9.7 microg/mL in whole blood (mean+/-SD, n = 50).
      The ELISA can be used to examine various hematologic disorders with abnormal red
      cell size and cell counts, and to detect BPGM enzymopathy in human erythrocytes.

PMID- 9773956
TI  - Development of a highly sensitive and specific two-site enzyme immunoassay for
      parathyroid hormone (1-34): application to pharmacokinetic study on intranasal
      parathyroid hormone (1-34) in human.
AB  - A highly sensitive and specific two-site enzyme immunoassay for parathyroid
      hormone (1-34) (PTH(1-34)) and its usability for the pharmacokinetic study are
      described. Plasma samples were incubated simultaneously with 2,4
      dinitrophenylated anti-PTH(1-34) IgG and anti-PTH(1-34) Fab'-beta-D-galactosidase
      conjugate. The immune complex formed of the three components was trapped onto
      (anti-2,4-dinitrophenyl group) IgG-coated polystyrene balls. beta-D-Galactosidase
      activity bound to the polystyrene balls was assayed by fluorometry. The practical
      detection limit of PTH(1-34) was 50 fg (12 amol)/0.05 ml of sample and 1 pg/ml as
      the concentration and practically no interference occurred by PTH(1-84) and PTH
      related protein (1-34) up to 300 pg/ml and 10 ng/ml, respectively. The
      application of this method has enabled us to directly estimate the
      bioavailability of PTH(1-34) dosed intranasally at the prescribed level (0.090
      mg). The pharmacokinetic parameters of the intranasal PTH(1-34) (n = 4) thus
      estimated were as follows: the area under the plasma concentration-time curve
      (AUC) = 20,500+/-15,900(SD) pg.min/ml; the mean residence time (MRT) = 194+/
      16.3(SD) min; and the maximal concentration (Cmax) = 98+/-51 (SD) pg/ml with the
      maximal time (Tmax) = 35.0+/-12.2(SD) min.

PMID- 9773957
TI  - Role of cardiac troponin I in the evaluation of myocardial injury.
AB  - Cardiac troponin I (cTnl) is highly specific for cardiac muscle. In this study,
      we compared the utility of CK and CK-MB index versus cTnl in the assessment of
      myocardial infarction in 155 patients being evaluated for myocardial damage. As a
      cardiac marker for MI, Troponin I seems to be superior to CK-MB. In the subset of
      patients with renal disease, cTnl has definite advantages over CK-MB. In
      addition, the use of cTnl has the potential to replace the measurement of lactate
      dehydrogenase isoenzymes.

PMID- 9773958
TI  - Comparison of instrument-read dipsticks for albumin and creatinine in urine with
      visual results and quantitative methods.
AB  - Three hospital sites evaluated the Bayer two-pad urine dipstick as a screening
      test for microalbuminuria. One pad estimates albumin concentrations between 10
      and 150 mg/L, and the second estimates creatinine values between 300 and 3,000
      mg/L. The Boehringer Mannheim (BMD) Micral dipstick was also compared and
      evaluated. The accuracy of the dipsticks was judged by comparison with cuvet
      based immunonephelometry for albumin and to standard rate-Jaffe methods for
      creatinine; these assays were well standardized and controlled and were assumed
      to give accurate values. Precision of these methods and that of the dipsticks was
      determined by multiple assays of control materials. Visual or instrument
      (Clinitek 50 or 100) evaluation of the Bayer or visual checks of the BMD albumin
      dipstick pad with patients' urines gave clinically acceptable accuracy. The
      albumin/creatinine ratio from the Bayer dipsticks gave better accuracy for
      albumin excretion than the albumin pads alone from either manufacturer. This
      ratio should permit making a good estimate of the 24-hr albumin excretion in a
      randomly collected urine.

PMID- 9773959
TI  - Biochemical assay for AD7C-NTP in urine as an Alzheimer's disease marker.
AB  - A reliable and specific immunoassay has been developed to detect and measure AD7C
      NTP, a biochemical marker for Alzheimer's disease, in urine. The urine samples
      are first processed by centrifugation and ultrafiltration to fractionate and
      concentrate AD7C-NTP. The urinaryAD7C-NTP has the same molecular weight asAD7C
      NTP in brain and cerebrospinal fluid by size exclusion chromatography. It has
      also retained the binding properties to the monoclonal and polyclonal antibodies
      developed against recombinantly produced AD7C-NTP. This assay is an enzyme linked
      sandwich immunoassay (ELSIA) using 96 well microtiter plates. The plate surface
      is coated with a monoclonal antibody (N314) which has a high affinity and
      specificity for AD7C-NTP, capturing it effectively from the samples. The
      detection was achieved using a polyclonal antibody (ADRI). The utility of the
      assay has been demonstrated using urine specimens from Alzheimer's disease (AD)
      patients and non-Alzheimer's controls. UrinaryAD7C-NTP in the AD group (2.5
      ng/mL, n=66) was significantly higher than the non-AD group (0.8 ng/mL, n=134).
      Using 1.5 ng/mL as cut off, in this patient population, specificity and
      sensitivity of urinary AD7C-NTP were comparable to CSFAD7C-NTP.

PMID- 9773961
TI  - Standardized measurement of major immunoglobulin class (IgG, IgA, and IgM)
      antibodies to beta2glycoprotein I in patients with antiphospholipid syndrome.
AB  - Patients with the antiphospholipid syndrome (APS) have autoantibodies directed
      against epitopes on beta2 glycoprotein I (beta2GPI). We describe herein the
      performance characteristics of standardized enzyme-linked immunosorbent assays
      (ELISAs) for anti-beta2GPI of the three major immunoglobulin classes: IgG, IgA,
      and IgM. All three assays generated highly linear standard curves (5 points, r >
      or = 0.993 for each); precision was excellent both intra-assay and run-to-run,
      with coefficients of variation (CV) ranging from 2.3% to 6.6%. Values for IgG
      anti-beta2GPI correlated strongly with those obtained by an earlier method (r =
      0.80, P< 0.0001). A study group consisting of 203 healthy subjects was used to
      generate percentile-based reference intervals for all three classes of anti
      beta2GPI. APS subjects' anti-beta2GPI were found to differ significantly (P
      <0.0001 for each) from those of the control population. All three assays
      correlated well with beta2GPI-dependent anticardiolipin antibody (aCL)
      measurements; IgG: r = 0.94 (P <0.0001), for IgA: r = 0.82 (P<0.001) and for IgM:
      r = 0.84 (P<0.0001). We suggest that these ELISAs may provide valuable
      standardized measurements of IgG, IgA, and IgM anti-P2GPI.

PMID- 9773960
TI  - Establishment of monoclonal antibody against human Apo B-48 and measurement of
      Apo B-48 in serum by ELISA method.
AB  - The elevation of chylomicrons and chylomicron remnants in plasma would lead to
      hyperlipidemia and other complications. Apo B-48, which is translated and
      produced in the adult intestine from the same gene as Apo B-100, is considered to
      be an essential component of chylomicrons and chylomicron remnants. Using a
      peptide representing human Apo B-48 C-terminal sequence as immunogen, we
      established a monoclonal antibody, B48-151, against human Apo B-48. The specific
      reactivity for Apo B-48 of this monoclonal antibody was confirmed using Western
      blot analysis of human plasma in fractions isolated as chylomicron and VLDL.
      Then, we developed a simple sandwich ELISA method for the detection of human Apo
      B-48 in serum by combining B48-151 as capturing antibody and HRP-conjugated
      polyclonal antibodies for Apo B as signaling antibody. The established sandwich
      ELISA constitutes a simple method to monitorApo B-48 level in chylomicrons and
      chylomicron remnants in human serum.

PMID- 9773962
TI  - Isolation of the intact molecule and ectodomain of C-erbB-2 oncoprotein from SK
      BR-3 cells and development of immunoassays on microplate.
AB  - We isolated both the intact molecule (p185) and the ectodomain (p120) of c-erbB-2
      oncoprotein from SK-BR-3 breast tumor cells. The p120 was extracted from the
      cells by 0.05 M phosphate buffer, pH 7.2, whereas the extraction of the p185
      required the presence of a detergent, such as 1% Triton X-100 in 0.05 M Tris
      buffer. Protease inhibitors were also included in the extraction buffer during
      the isolation of p185 in order to prevent cleavage of p185 to p120 by an unknown
      protease apparently also present in the extract. In case there was any p120 in
      the p185 preparation, the p120 could be separated from p185 by chromatography on
      a Superose 12 column. Using the p120 and p185 as calibrators, we have established
      two microplate sandwich immunoassays: one measures both p185 and p120 (total
      assay) and the other is specific for the p185. Since capturing and detecting
      antibodies used in the total assay react against the extracellular domain of the
      c-erbB-2 oncoprotein, they can therefore be used to measure the p120 in serum and
      p185 in breast tumor tissue cytosol. On the other hand, the p185 specific assay
      uses the capturing antibody against the cytosolic domain of the oncoprotein and
      consequently can only measure p185 in breast tumor tissue cytosol.

PMID- 9773963
TI  - Impact of assay parameters on the accuracy of free PSA test: source and stability
      of calibrator, calibration curve fitting, and level of total PSA in the serum.
AB  - The measurement of PSA is recommended for men over 50 years of age for screening
      of prostate cancer. However, proper differentiation of prostate cancer from
      benign prostate hyperplasia (BPH) relies on an accurate measurement of free PSA
      (fPSA) and a correct calculation of percent fPSA. Because of the extremely low
      concentration of fPSA in the serum, any slight deviation from its true value may
      produce large errors in percent fPSA calculated. Therefore, we undertook a study
      examining carefully those parameters of the fPSA assay which might affect the
      fPSA determination. We found that the integrity of the calibrator, the computer
      curve-fitting program selected, the source of the calibrator, and the total PSA
      or fPSA + PSA complexes (tPSA) concentration of the specimen all had an impact on
      the accuracy of the fPSA value assayed. We found that an examination of the slope
      of the calibration curve was important to reveal whether the calibrator had or
      had not been denatured during storage. We also found that the 4-parameter cure
      fitting program was best suited for plotting the fPSA calibration curve. The
      calibrator we isolated from LNCaP cells was acceptable for our assay because it
      had an affinity for the assay antibody very similar to that of serum fPSA. We
      also determined the effect of tPSA concentration on the fPSA determinations and
      found that within the concentration range of 4-10 ng/mL the impact on the percent
      fPSA calculated was not significant. We believe that our assay produces accurate
      fPSA values when all these assay parameters are well controlled.

PMID- 9773964
TI  - Flow cytometric findings in the floral variant of follicular lymphoma.
AB  - The floral variant of follicular lymphoma (FL-F) is an unusual variant of
      follicular lymphoma. The malignant "follicles" have an unusual "floral"
      appearance due to the proliferation of surrounding and infiltrating small
      lymphocytes. This variant of malignant lymphoma has been supported by
      immunohistochemical immunophenotyping and gene-rearrangement studies; however,
      the flow cytometric findings have not previously been described. We report the
      flow cytometric findings in two cases of FL-F. The surrounding and infiltrating
      small lymphocytes represented mantle cells which, in one case, obscured
      monoclonality in the lymphocyte region. The monoclonal B-cells were CD10+,
      supporting a follicular center cell origin.

PMID- 9773965
TI  - Development of an assay for modulating anti-acetylcholine receptor autoantibodies
      using human rhabdomyosarcoma cell line.
AB  - Three types of autoantibodies against the acetylcholine receptors (AChR) of
      skeletal muscle are detectable in patients with myasthenia gravis including
      binding, blocking, and modulating anti-AChR antibodies. Modulating autoantibodies
      correlate best with the severity of the disease, but are also technically most
      difficult to measure because the assay generally requires fresh human muscle
      cells. We have developed an assay for the modulation of anti-AChR antibodies
      using a rhabdomyosarcoma (RD) cell line expressing AChR on the cell surface. By
      decreasing the FetalClone III serum from 10% to 0.5% in Eagles Minimal Essential
      Medium (EMEM) we were able to increase the number of AChR on RD cells to meet the
      need of sensitivity of the assay. The extent of modulation was determined as the
      percent of AChR internalized in the presence or absence of modulating
      autoantibodies. Less than 6% modulation was found with the normal serum (n = 42).
      The CVs of both the intra- and day-to-day precision were less than 20%. When
      clinical samples (n = 105) were assayed in our laboratory and also at Nichols
      Institute, a correlation coefficient of 0.816 was obtained. The selection of RD
      cell line, the success of increasing the expression of the AChR on RD cells and
      the use of 125I alpha-bungarotoxin of high specific activity allowed the
      establishment of an assay which can be used in routine clinical laboratory for
      the measurement of modulating anti-AChR autoantibodies for the management of
      patients with myasthenia gravis.

PMID- 9773966
TI  - Evaluation of a line immunoblot assay for detection of antibodies recognizing
      extractable nuclear antigens.
AB  - Sera (n = 90) giving positive results in a screening test for antibodies to
      extractable nuclear antigens (ENAs) were tested in a line immunoblot assay that
      measures antibody reactivity with individual ENAs in a single test field. Results
      were then compared to those obtained in monospecific ENA antibody enzyme
      immunoassays (EIAs). Discordant results were resolved by immunodiffusion. Of 540
      result pairs (90 sera tested for 6 ENAs [Sm/RNP, Sm, SSA, SSB, Scl-70, Jo-1]),
      509 (94%) showed concordance. Immunodiffusion resolved 28 of 31 discordant result
      pairs in favor of the immunoblot result. After resolution of discordant data, the
      immunoblot assay exhibited 100% sensitivity for all ENA antibodies except those
      recognizing Scl-70, for which the sensitivity was 89%; specificity was over 96%
      for all 6 ENA antibodies. These findings show that a line immunoblot assay for
      the characterization of ENA antibodies yields results comparable to those
      obtained using monospecific ENA antibody EIAs. The immunoblot assay is easier and
      less expensive to perform due to its utilization of a single test field.

PMID- 9773967
TI  - Normal variants and pitfalls in magnetic resonance imaging of the ankle and foot.
AB  - Distinction of normal from disease is one of the principal tenets in magnetic
      resonance imaging (MRI) interpretation of the foot and ankle. Therefore,
      familiarity with normal anatomic variants and pitfalls in the foot and ankle is
      crucial for accurate diagnostic analysis of MR images. This article will focus on
      outlining variants and MRI interpretation pitfalls of the tendons, muscles,
      bones, ligaments, and other miscellaneous structures of the foot and ankle.

PMID- 9773968
TI  - Magnetic resonance imaging of the peroneal tendons.
AB  - Injuries of the peroneal tendons include tendinosis, tenosynovitis, tears, and
      dislocation. These injuries are being detected with greater frequency since the
      advent of MRI. After a review of the normal MRI anatomy of the peroneal tendons,
      this article will focus on the MR features of peroneal tendon disorders in the
      foot and ankle.

PMID- 9773969
TI  - Magnetic resonance imaging arthrography of the ankle.
AB  - Magnetic resonance imaging (MRI) arthrography of the ankle is a useful diagnostic
      modality in the detection and staging of lateral ankle ligament tears,
      particularly in patients who fail to respond to conservative management. MRI
      arthrography also may be helpful in determining the extent of ligamentous injury
      in professional athletes, for whom immediate surgical repair may be the initial
      treatment. Preoperative planning is optimized with MRI arthrography. Frequently,
      alternative diagnoses may be made for conditions that can simulate lateral
      ligamentous injury, thus obviating the need for diagnostic arthroscopy.

PMID- 9773970
TI  - Diabetic foot and neuroarthropathy: magnetic resonance imaging evaluation.
AB  - Neuropathic osteoarthropathy occurs commonly in patients with long-standing
      diabetes mellitus and is one of the leading causes of debilitating complications
      of the foot. In this article, the pathologic and radiologic features of
      neuropathic joint disease are reviewed, with an emphasis on MRI.

PMID- 9773971
TI  - Painful syndromes around the ankle and foot: magnetic resonance imaging
      evaluation.
AB  - There are many causes for pain in the region of the ankle and foot. Magnetic
      resonance imaging can be useful for identifying some of these causes. This
      article addresses the following etiologies: tarsal tunnel syndrome, sinus tarsi
      syndrome, osteochondral and stress fractures, the painful accessory navicular,
      osteonecrosis of the talus, navicular and metatarsal heads, posterior impingement
      syndrome, bursitis, accessory muscles, Morton's neuroma, and plantar
      fibromatosis.

PMID- 9773972
TI  - Analysis of differentiation-induced expression mechanisms of thyrotropin receptor
      gene in adipocytes.
AB  - Rat adipose tissue, as well as differentiated 3T3-L1 cells, has been shown to
      express TSH receptor (TSHR) mRNA in amounts approaching those in the thyroid. We
      investigated the molecular mechanisms of TSHR gene expression in adipose cells.
      Primer extension and cloned cDNA sequences showed that transcription of the TSHR
      gene in rat adipose tissue was from multiple start sites clustered between -89 to
      -68 bp and almost identical to those in FRTL-5 thyroid cells. By transient
      expression analysis, we localized, between -146 and -90 bp, a positive regulatory
      element, the activity of which was markedly increased after the differentiation
      of 3T3-L1 cells. Deoxyribonuclease I protection showed that nuclear extracts from
      differentiated 3T3-L1 cells strongly protected two sequences, from -146 to -127
      bp, including a cAMP response element-like sequence and from -112 to -106 bp
      containing a putative Ets-binding sequence. In differentiated 3T3-L1 cells,
      disruption or deletion of either sequence was found to result in the loss of
      enhancer activity, suggesting both elements may synergistically activate the TSHR
      promoter. Electrophoretic mobility shift analysis revealed the induction of new
      protein/DNA complexes formed either with the cAMP response element-like site or
      with putative Ets elements after the differentiation into adipocytes. In
      contrast, nuclear proteins, whose binding to DNA was diminished after the
      differentiation of 3T3-L1 cells, were found to interact with the site contiguous
      to the 5'-end of the putative Ets-binding sequence. Mutations of this binding
      site, which reduced the protein/DNA complex formation, increased TSHR promoter
      activity in undifferentiated cells. These observations suggested that
      differentiation-induced diminution of suppressor interactions may allow the
      enhancers to synergistically activate the transcription of TSHR gene in
      adipocytes.

PMID- 9773973
TI  - Structural requirements of the glucocorticoid and retinoic acid response units in
      the phosphoenolpyruvate carboxykinase gene promoter.
AB  - The phosphoenolpyruvate carboxykinase (PEPCK) gene promoter contains a
      glucocorticoid response unit (GRU) that includes three accessory factor-binding
      sites (AF1, AF2, and AF3), two glucocorticoid receptor-binding sites (GR1 and
      GR2), and a cAMP response element. All of these elements, and the proteins that
      bind to them, are required for a complete glucocorticoid response. The PEPCK
      promoter also contains a retinoic acid response unit (RARU) that consists of two
      retinoic acid response elements (RARE1 and RARE2) that bind retinoic acid
      receptor/9-cis-retinoic acid receptor heterodimers. The sequences of RARE1 and
      RARE2 coincide with those for AF1 and AF3, respectively. Thus, the PEPCK promoter
      can mediate different hormone responses through hormone response units that
      utilize common elements, but that bind different sets of proteins. We reasoned
      that each response might require a unique structural assembly and therefore
      tested how various arrangements of the PEPCK promoter affect the actions of
      either glucocorticoids or retinoic acid. The activation of the PEPCK gene in
      response to glucocorticoids requires a specific set of cis-acting elements that
      must be precisely positioned within the GRU. The distance between AF2 and GR1 is
      critical for the glucocorticoid response, and since the AF2 factor, HNF3,
      interacts with GR in vitro, this protein-protein interaction may be important for
      the glucocorticoid response. By contrast, the distance and orientation
      requirements of AF1 and AF3 with respect to GR1 are more flexible. In the case of
      the RARU, although the relative positions of RARE1 and RARE2 are important for
      the retinoic acid response, more tolerance for distance and stereospecific
      alignment between RARE1 and RARE2 is allowed. In addition, we show that the GRU
      and the RARU can act as a module, within a restricted region, in the context of
      the PEPCK promoter and in limited contexts of a heterologous promoter. These
      observations suggest that the structural requirements of the GRU and the RARU are
      different, and this may have important implications for how multiple hormonal
      signals are integrated through this promoter.

PMID- 9773975
TI  - Phosphorylation of the angiotensin II (AT1A) receptor carboxyl terminus: a role
      in receptor endocytosis.
AB  - The molecular mechanism of angiotensin II type I receptor (AT1) endocytosis is
      obscure, although the identification of an important serine/threonine rich region
      (Thr332Lys333Met334Ser335Thr336Leu337 Ser338) within the carboxyl terminus of the
      AT1A receptor subtype suggests that phosphorylation may be involved. In this
      study, we examined the phosphorylation and internalization of full-length AT1A
      receptors and compared this to receptors with truncations and mutations of the
      carboxyl terminus. Epitope-tagged full-length AT1A receptors, when transiently
      transfected in Chinese hamster ovary (CHO)-K1 cells, displayed a basal level of
      phosphorylation that was significantly enhanced by angiotensin II (Ang II)
      stimulation. Phosphorylation of AT1A receptors was progressively reduced by
      serial truncation of the carboxyl terminus, and truncation to Lys325, which
      removed the last 34 amino acids, almost completely inhibited Ang II-stimulated
      32P incorporation into the AT1A receptor. To investigate the correlation between
      receptor phosphorylation and endocytosis, an epitope-tagged mutant receptor was
      produced, in which the carboxyl-terminal residues, Thr332, Ser335, Thr336, and
      Ser338, previously identified as important for receptor internalization, were
      substituted with alanine. Compared with the wild-type receptor, this mutant
      displayed a clear reduction in Ang II-stimulated phosphorylation. Such a
      correlation was further strengthened by the novel observation that the Ang II
      peptide antagonist, Sar(1)Ile8-Ang II, which paradoxically causes internalization
      of wild-type AT1A receptors, also promoted their phosphorylation. In an attempt
      to directly relate phosphorylation of the carboxyl terminus to endocytosis, the
      internalization kinetics of wild-type AT1A receptors and receptors mutated within
      the Thr332-Ser338 region were compared. The four putative phosphorylation sites
      (Thr332, Ser335, Thr336, and Ser338) were substituted with either neutral
      [alanine (A)] or acidic amino acids [glutamic acid (E) and aspartic acid (D)],
      the former to prevent phosphorylation and the latter to reproduce the acidic
      charge created by phosphorylation. Wild-type AT1A receptors, expressed in Chinese
      hamster ovary cells, rapidly internalized after Ang II stimulation [t1/2 2.3 min;
      maximal level of internalization (Ymax) 78.2%], as did mutant receptors carrying
      single acidic substitutions (T332E, t1/2 2.7 min, Ymax 76.3%; S335D, t1/2 2.4
      min, Ymax 76.7%; T336E, t1/2 2.5 min, Ymax 78.2%; S338D, t1/2 2.6 min, Ymax
      78.4%). While acidic amino acid substitutions may simply be not as structurally
      disruptive as alanine mutations, we interpret the tolerance of a negative charge
      in this region as suggestive that phosphorylation may permit maximal
      internalization. Substitution of all four residues to alanine produced a receptor
      with markedly reduced internalization kinetics (T332A/S335A/T336A/S338A, t1/2
      10.1 min, Ymax 47.9%), while endocytosis was significantly rescued in the
      corresponding quadruple acidic mutant (T332E/S335D/T336E/S338D, t1/2 6.4 min,
      Ymax 53.4%). Double mutation of S335 and T336 to alanine also diminished the rate
      and extent of endocytosis (S335A/T336A, 3.9 min, Ymax 69.3%), while the analogous
      double acidic mutant displayed wild type-like endocytotic parameters
      (S335D/T336E, t1/2 2.6 min, Ymax 77.5%). Based on the apparent rescue of
      internalization by acidic amino acid substitutions in a region that we have
      identified as a site of Ang II-induced phosphorylation, we conclude that maximal
      endocytosis of the AT1A receptor requires phosphorylation within this
      serine/threonine-rich segment of the carboxyl terminus.

PMID- 9773974
TI  - Multiple promoter elements contribute to activity of the follicle-stimulating
      hormone receptor (FSHR) gene in testicular Sertoli cells.
AB  - The FSH receptor (FSHR) is expressed only in granulosa cells of the ovary and
      Sertoli cells of the testis. This highly specific pattern of gene expression
      asserts that transcriptional events unique to these two cell types are
      responsible for activation of the FSHR gene. We have characterized the promoter
      elements required for activity of the rat FSHR gene in a Sertoli cell line MSC-1,
      primary cultures of rat Sertoli cells, and two non-Sertoli cell lines. Transient
      transfection analysis of deletion and block replacement mutants identified
      several elements, both 5' and 3' to the transcriptional start sites, that are
      essential for full promoter activity in Sertoli cells. These studies confirmed
      the use of an important E box element (CACGTG), which had the single greatest
      impact on promoter function. Bases within the core CACGTG of the E box, as well
      as flanking sequences, were shown to be essential for its function.
      Electrophoretic mobility shift assays identified both upstream stimulatory factor
      1 (USF1) and USF2 as primary components of the complexes binding the E box.
      Sequence requirements for USF binding in vitro modestly diverged from the
      sequence requirements for in vivo function of the element. Comparison of the E
      box binding proteins in different cell types revealed that similar proteins bind
      the E box in Sertoli and non-Sertoli cell lines. Extracts from primary cultures
      of rat and mouse Sertoli cells have a second E box-binding complex that cross
      reacts with USF antibodies that is not present in the cell lines.

PMID- 9773976
TI  - Functional interaction between the estrogen receptor and CTF1: analysis of the
      vitellogenin gene B1 promoter in yeast.
AB  - Eukaryotic gene expression depends on a complex interplay between the
      transcriptional apparatus and chromatin structure. We report here a yeast model
      system for investigating the functional interaction between the human estrogen
      receptor (hER) and CTF1, a member of the CTF/NFI transcription factor family. We
      show that a CTF1-fusion protein and the hER transactivate a synthetic promoter in
      yeast in a synergistic manner. This interaction requires the proline-rich
      transactivation domain of CTF1. When the natural estrogen-dependent vitellogenin
      B1 promoter is tested in yeast, CTF1 and CTF1-fusion proteins are unable to
      activate transcription, and no synergy is observed between hER, which activates
      the B1 promoter, and these factors. Chromatin structure analysis on this promoter
      reveals positioned nucleosomes at -430 to -270 (+/-20 bp) and at -270 to - 100
      (+/-20 bp) relative to the start site of transcription. The positions of the
      nucleosomes remain unchanged upon hormone-dependent transcriptional activation of
      the promoter, and the more proximal nucleosome appears to mask the CTF/NFI site
      located at - 101 to -114. We conclude that a functional interaction of hER with
      the estrogen response element located upstream of a basal promoter occurs in
      yeast despite the nucleosomal organization of this promoter, whereas the
      interaction of CTF1 with its target site is apparently precluded by a nucleosome.

PMID- 9773977
TI  - Protein-protein interaction domains and the heterodimerization of thyroid hormone
      receptor variant alpha2 with retinoid X receptors.
AB  - Heterodimerization between thyroid hormone receptors (TRs) and retinoid X
      receptors (RXRs) is mediated by a weak dimerization interface within the DNA-
      binding domains (DBDs) and a strong interface within the C-terminal ligand-
      binding domains of the receptors. Previous studies have shown that the conserved
      ninth heptad in the TR ligand-binding domain appears to play a critical role in
      heterodimerization with RXR. However, despite lacking the full ninth heptad, TR
      variant alpha2 (TRv alpha2) can heterodimerize with RXR on specific direct repeat
      response elements, but not on palindromic elements or in solution. Two
      possibilities may account for TRv alpha2-RXR heterodimerization on direct
      repeats. First, the DBD of TRv alpha2 may play a critical role in
      heterodimerization with RXR. Second, a specific sequence within the unique C
      terminus of TRv alpha2 may promote the formation of TRv alpha2-RXR heterodimers.
      In this study, we used receptor chimeras in which the DBD of RXR was replaced by
      either the TR DBD or an unrelated DBD from the metalloregulatory transcription
      factor AMT1 to address the role of the DBD dimerization interface in TRv alpha2
      RXR heterodimerization. Gel mobility shift analyses showed that whereas TR alpha1
      formed heterodimers with these chimeras, TRv alpha2 failed to do so. Deletion of
      the unique C terminus of TRv alpha2 had only a marginal effect on
      heterodimerization with RXR. Mutations within the DBD dimerization interface
      abolished heterodimerization of full-length TRv alpha2 with RXR but only
      marginally affected heterodimerization of full-length TR alpha1 with RXR. These
      data support the hypothesis that the TR-RXR DBD dimerization interface plays a
      critical role in TRv alpha2-RXR heterodimerization. Additional data show that the
      amino acid residues that make direct TR-RXR contacts within the DBDs also may
      play a role in receptor monomer binding to DNA, since mutations within these
      residues severely impair this interaction.

PMID- 9773978
TI  - Inhibition of estrogen receptor action by the orphan receptor SHP (short
      heterodimer partner).
AB  - SHP (short heterodimer partner) is an unusual orphan receptor that lacks a
      conventional DNA-binding domain. Previous results have shown that it interacts
      with several other nuclear hormone receptors, including the retinoid and thyroid
      hormone receptors, and inhibits their ligand-dependent transcriptional
      activation. Here we show that SHP also interacts with estrogen receptors and
      inhibits their function. In mammalian and yeast two-hybrid systems as well as
      glutathione-S-transferase pull-down assays, SHP interacts specifically with
      estrogen receptor-alpha (ERalpha) in an agonist-dependent manner. The same assay
      systems using various deletion mutants of SHP map the interaction domain with
      ERalpha to the same SHP sequences required for interaction with the nonsteroid
      hormone receptors such as retinoid X receptor and thyroid hormone receptor. In
      transient cotransfection assays, SHP inhibits estradiol -dependent activation by
      ERalpha by about 5-fold. In contrast, SHP interacts with ERbeta independent of
      ligand and reduces its ability to activate transcription by only 50%. These data
      suggest that SHP functions to regulate estrogen signaling through a direct
      interaction with ERalpha.

PMID- 9773979
TI  - Catalytic cleavage of the androgen receptor messenger RNA and functional
      inhibition of androgen receptor activity by a hammerhead ribozyme.
AB  - Androgen receptor (AR) plays a key role in cell growth both in the normal
      prostate and in prostate cancer. Androgen ablation and prolonged antiandrogen
      therapy can give rise to AR-dependent prostate tumors, which nonetheless can grow
      in the androgen-deprived milieu. Here we describe the ribozyme approach to
      selectively degrading the AR mRNA and thereby inhibiting AR function. A trans
      acting hammerhead ribozyme was designed to cleave the rat AR mRNA at the position
      +1827/ 1828, a region predicted to be minimally involved in generating stable
      secondary structures. Using AR mRNA fragments as substrates, it was established
      that this ribozyme can specifically cleave the RNA target in a sequence-specific
      manner. Kinetic experiments determined a Km for the substrate of 77 nM and a
      kcat/Km value of 1.8 x 10(7) M(-1) x min(-1), suggesting a catalytic efficiency
      similar to that of protein enzymes such as the relatively nonspecific
      ribonuclease A and a sequence-specific endonuclease EcoRI. Transient
      cotransfections of prostate-derived PC3 cells with three plasmids, an AR
      inducible chloramphenicol acetyltransferase (CAT) reporter, an AR expression
      vector, and a ribozyme expression vector, showed that the ribozyme was capable of
      reducing the functional activity of AR. At an equimolar ratio of the AR
      expression plasmid to ribozyme expression plasmid, androgen-inducible CAT
      activity was inhibited 70%. Similar extents of inhibition were also observed at
      the cellular mRNA level using ribonuclease protection assays, indicating that the
      ribozyme functioned as an AR mRNA cleaving enzyme in cellulo. Immunocytochemical
      examination revealed a decline of AR immunoreactivity in ribozyme-transfected
      cells. In addition, no morphologically detectable cellular abnormalities were
      associated with ribozyme expression, indicating the absence of deleterious side
      effects. These results offer a new avenue for the control of AR function and cell
      growth, especially in the case of androgen-resistant, but AR-dependent, prostate
      cancer cells.

PMID- 9773980
TI  - Two separate NCoR (nuclear receptor corepressor) interaction domains mediate
      corepressor action on thyroid hormone response elements.
AB  - The nuclear corepressor (NCoR) binds to the thyroid hormone receptor (TR) in the
      absence of ligand. NCoR-TR interactions are mediated by two interaction domains
      in the C-terminal portion of NCoR. Binding of NCoR to TR results in ligand
      independent repression on positive thyroid hormone response elements. The
      interactions between NCoR interaction domains and TR on DNA response elements,
      however, have not been well characterized. We have found that both interaction
      domains are capable of binding TR on thyroid hormone response elements. In
      addition, the NCoR interaction domains interact much more strongly with the TR
      than those present in the silencing mediator of retinoic acid and TRs (SMRT).
      Furthermore, deletion of either NCoR interaction domain does not significantly
      impair ligand-independent effects on positive or negative thyroid hormone
      response elements. Finally, both NCoR interaction domains appear to
      preferentially bind TR homodimer over TR-retinoid X receptor heterodimer in
      electrophoretic mobility shift assays. These data suggest that either NCoR
      interaction domain is capable of mediating the ligand-independent effects of TR
      on positive and negative thyroid hormone response elements.

PMID- 9773981
TI  - p300/CREB-binding protein enhances the prolactin-mediated transcriptional
      induction through direct interaction with the transactivation domain of Stat5,
      but does not participate in the Stat5-mediated suppression of the glucocorticoid
      response.
AB  - Stat5 was discovered as a PRL-induced member of the Stat (signal transducer and
      activator of transcription) family. Its induction by many other cytokines and
      interleukins suggests that Stat5 plays a crucial role not only in mammary
      epithelial, but also in hematopoietic cells. Cell type- and promoter-specific
      functions of Stat5 are most likely modulated by the interaction with other
      transcription factors. We recently showed cross-talk between Stat5 and the
      glucocorticoid receptor. The activated glucocorticoid receptor forms a complex
      with Stat5 and enhances Stat5-mediated transcriptional induction. Conversely,
      Stat5 diminishes the induction of glucocorticoid-responsive genes. Here, we
      investigated the role of p300/CBP(CREB-binding protein), a transcriptional
      coactivator of several groups of transcription factors, in Stat5-mediated
      transactivation and in the cross-talk between Stat5 and the glucocorticoid
      receptor. p300/ CBP acts as a coactivator of Stat5. Its ectopic expression
      enhances PRL-induced Stat5-mediated transcriptional activation. Consistent with
      this observation, we find that the adenovirus E1A protein, which binds to
      p300/CBP, suppresses Stat5-induced transcriptional activation. This inhibition
      requires the Stat5 transactivation domain and the p300/CBP binding site of E1A.
      Coimmunoprecipitation and mammalian two-hybrid assays demonstrate a direct
      interaction between the carboxyl-terminal transactivation domain of Stat5 and
      p300/CBP. p300/CBP also positively interacts with the glucocorticoid receptor and
      enhances glucocorticoid receptor-dependent transcriptional activation of the
      mouse mammary tumor virus-long terminal repeat promoter. Overexpression of
      p300/CBP does not counteract the Stat5-mediated inhibition of glucocorticoid
      receptor-dependent transactivation, i.e. the repression of the glucocorticoid
      response by Stat5 is not a consequence of competition for limiting amounts of
      p300/CBP.

PMID- 9773982
TI  - Nuclear receptors have distinct affinities for coactivators: characterization by
      fluorescence resonance energy transfer.
AB  - Ligand-dependent interactions between nuclear receptors and members of a family
      of nuclear receptor coactivators are associated with transcriptional activation.
      Here we used fluorescence resonance energy transfer (FRET) as an approach for
      detecting and quantitating such interactions. Using the ligand binding domain
      (LBD) of peroxisome proliferator-activated receptor (PPARgamma) as a model, known
      agonists (thiazolidinediones and delta12, 14-PGJ2) induced a specific interaction
      resulting in FRET between the fluorescently labeled LBD and fluorescently labeled
      coactivators [CREB-binding protein (CBP) or steroid receptor coactivator-1 (SRC
      1)]. Specific energy transfer was dose dependent; individual ligands displayed
      distinct potency and maximal FRET profiles that were identical when results
      obtained using CBP vs. SRC-1 were compared. In addition, half-maximally effective
      agonist concentrations (EC59s) correlated well with reported results using cell
      based assays. A site-directed AF2 mutant of PPARgamma (E471A) that abrogated
      ligand-stimulated transcription in transfected cells also failed to induce ligand
      mediated FRET between PPARgamma LBD and CBP or SRC-1. Using estrogen receptor
      (ERalpha) as an alternative system, known agonists induced an interaction between
      ERalpha LBD and SRC-1, whereas ER antagonists disrupted agonist-induced
      interaction of ERalpha with SRC-1. In the presence of saturating agonist
      concentrations, unlabeled CBP or SRC-1 was used to compete with fluorescently
      labeled coactivators with saturation kinetics. Relative affinities for the
      individual receptor-coactivator pairs were determined as follows: PPARgamma-CBP =
      ERalpha-SRC-1 > PPARgamma-SRC-1 >> ERalpha-CBP. CONCLUSIONS: 1) FRET-based
      coactivator association is a novel approach for characterizing nuclear receptor
      agonists or antagonists; individual ligands display potencies that are predictive
      of in vivo effects and distinct profiles of maximal activity that are suggestive
      of alternative receptor conformations. 2) PPARgamma interacts with both CBP and
      SRC-1; transcriptional activation and coactivator association are AF2 dependent.
      3) Nuclear receptor LBDs have distinct affinities for individual coactivators;
      thus, PPARgamma has a greater apparent affinity for CBP than for SRC-1, whereas
      ERalpha interacts preferentially with SRC-1 but very weakly with CBP.

PMID- 9773983
TI  - Estrogen receptor activation function 1 works by binding p160 coactivator
      proteins.
AB  - Estrogen receptor-alpha contains two transactivation functions, a weak
      constitutive activation function (AF-1) and a hormone-dependent activation
      function (AF-2). AF-2 works by recruiting a large coactivator complex, composed
      of one or more p160s, CREB-binding protein (CBP)/p300, and P/CAF (p300 and CBP
      associated factor), via direct contacts with the p160s. We report here that
      independent AF-1 activity also requires p160 contacts. Unlike AF-2, which binds
      signature NR boxes in the center of the p160 molecule, AF-1 binds to sequences
      near the p160 C terminus. We propose that the ability of AF-1 and AF-2 to
      interact with separate surfaces of the same coactivator is important for the
      ability of these transactivation functions to synergize.

PMID- 9773984
TI  - Characterization of a nuclear deformed epidermal autoregulatory factor-1 (DEAF-1)
      related (NUDR) transcriptional regulator protein.
AB  - A monkey kidney cDNA that encodes a nuclear regulatory factor was identified by
      expression and affinity binding to a synthetic retinoic acid response element
      (RARE) and was used to isolate human placental and rat germ cell cDNAs by
      hybridization. The cDNAs encode a 59-kDa protein [nuclear DEAF-1-related (NUDR)]
      which shows sequence similarity to the Drosophila Deformed epidermal
      autoregulatory factor-1 (DEAF-1), a nonhomeodomain cofactor of embryonic Deformed
      gene expression. Similarities to other proteins indicate five functional domains
      in NUDR including an alanine-rich region prevalent in developmental transcription
      factors, a domain found in the promyelocytic leukemia-associated SP100 proteins,
      and a zinc finger homology domain associated with the AML1/MTG8 oncoprotein.
      Although NUDR mRNA displayed a wide tissue distribution in rats, elevated levels
      of protein were only observed in testicular germ cells, developing fetus, and
      transformed cell lines. Nuclear localization of NUDR was demonstrated by
      immunocytochemistry and by a green fluorescent protein-NUDR fusion protein. Site
      directed mutagenesis of a nuclear localization signal resulted in cytoplasmic
      localization of the protein and eliminated NUDR-dependent transcriptional
      activation. Recombinant NUDR protein showed affinity for the RARE in mobility
      shifts; however it was efficiently displaced by retinoic acid receptor
      (RAR)/retinoid X receptor (RXR) complexes. In transient transfections, NUDR
      produced up to 26-fold inductions of a human proenkephalin promoter-reporter
      plasmid, with minimal effects on the promoters for prodynorphin or thymidine
      kinase. Placement of a RARE on the proenkephalin promoter increased NUDR
      dependent activation to 41-fold, but this RARE-dependent increase was not
      transferable to a thymidine kinase promoter. Recombinant NUDR protein showed
      minimal binding affinity for proenkephalin promoter sequences, but was able to
      select DNA sequences from a random oligonucleotide library that had similar core
      binding motifs (TTCG) as those recognized by DEAF-1. This motif is also present
      between the half-sites of several endogenous RAREs. The derived consensus-
      binding motif recognized by NUDR (TTCGGGNNTTTCCGG) was confirmed by mobility
      shift and deoxyribonuclease I (DNase I) protection assays; however, the consensus
      sequence was also unable to confer NUDR-dependent transcriptional activation to
      the thymidine kinase promoter. Our data suggests that NUDR may activate
      transcription independently of promoter binding, perhaps through protein-protein
      interaction with basal transcription factors, or by activation of secondary
      factors. The sequence and functional similarities between NUDR and DEAF-1 suggest
      that NUDR may also act as a cofactor to regulate the transcription of genes
      during fetal development or differentiation of testicular cells.

PMID- 9773985
TI  - Dissociation of early folding events from assembly of the human lutropin beta
      subunit.
AB  - The human LH of the anterior pituitary is a member of the glycoprotein hormone
      family that includes FSH, TSH, and placental CG. All are noncovalently bound
      heterodimers that share a common alpha-subunit and beta-subunits that confer
      biological specificity. LHbeta and CGbeta share more than 80% amino acid sequence
      identity; however, in transfected Chinese hamster ovary (CHO) cells, LHbeta
      assembles with the alpha-subunit more slowly than does hCGbeta, and only a
      fraction of the LHbeta synthesized is secreted, whereas CGbeta is secreted
      efficiently. To understand why the assembly and secretion of these related beta
      subunits differ, we studied the folding of LHbeta in CHO cells transfected with
      either the LHbeta gene alone, or in cells cotransfected with the gene expressing
      the common alpha-subunit, and compared our findings to those previously seen for
      CG. We found that the rate of conversion of the earliest detectable folding
      intermediate of LH, pbeta1, to the second major folding form, pbeta2, did not
      differ significantly from the pbeta1-to-pbeta2 conversion of CGbeta, suggesting
      that variations between the intracellular fates of the two beta-subunits cannot
      be explained by differences in the rates of their early folding steps. Rather, we
      discovered that unlike CGbeta, where the folding to pbeta2 results in an assembly
      competent product, apparently greater than 90% of the LH pbeta2 recovered from
      LHbeta-transfected CHO cells was assembly incompetent, accounting for inefficient
      LHbeta assembly with the alpha-subunit. Using the formation of disulfide (S-S)
      bonds as an index, we observed that, in contrast to CGbeta, all 12 LHbeta
      cysteine residues formed S-S linkages as soon as pbeta2 was detected. Attempts to
      facilitate LH assembly with protein disulfide isomerase in vitro using LH pbeta2
      and excess urinary alpha-subunit as substrate were unsuccessful, although protein
      disulfide isomerase did facilitate CG assembly in this assay. Moreover, unlike
      CGbeta, LHbeta homodimers were recovered from transfected CHO cells. Taken
      together, these data suggest that differences seen in the rate and extent of LH
      assembly and secretion, as compared to those of CG, reflect conformational
      differences between the folding intermediates of the respective beta-subunits.

PMID- 9773987
TI  - Primary unilateral cleft nose correction: a 10-year follow-up.
AB  - Primary nasal correction at the time of rotation-advancement of the lip has been
      rendered practical by developing a symmetrical nasal platform by presurgical
      orthodontics and a gingivoperiosteoplasty. The nasal correction involves
      unilateral columella lengthening, alar cartilage positioning, and alar base
      cinching to present a nose within normal limits. This is accomplished before the
      age of recall, and by avoiding retention of the nasal deformity through
      childhood, it by-passes the ridicule that invariably accompanies it.

PMID- 9773986
TI  - Transforming growth factor-beta in thermally injured patients with hypertrophic
      scars: effects of interferon alpha-2b.
AB  - Hypertrophic scarring is a common dermal fibroproliferative disorder that leads
      to poor quality wound healing, prolongs rehabilitation, and increases morbidity
      following major thermal and other injuries to the deep dermis. Local and systemic
      transforming growth factor (TGF)-beta has been implicated as a fibrogenic
      cytokine in the pathogenesis of many fibrotic disorders, whereas interferon (IFN)
      alpha-2b may improve the pathologic features of dermal fibrosis directly or by
      antagonizing the effects of TGF-beta and histamine. Nine patients with severe
      hypertrophic scarring were evaluated for 8 weeks before treatment with
      subcutaneous recombinant IFN alpha-2b, 2 x 10(6) IU three times per week for 24
      weeks. Clinical assessment was performed using standardized photography, a burn
      scar assessment tool, and serial scar volume measurements. Monthly measurements
      of serum TGF-beta and plasma Ntau-methylhistamine were made prior to, during, and
      after IFN alpha-2b therapy and compared with 27 age-matched controls. Serial
      biopsies of the hypertrophic scars and normal skin were performed for evaluation
      of mast cell numbers. Significant improvement in scar assessment occurred in 7 of
      9 patients, and 3 of 9 demonstrated significant reductions in scar volume with
      interferon therapy beyond that occurring during the 8-week control period. For
      the entire group, mean rates of improvement were significantly better during
      interferon therapy with no recurrence following treatment. Before interferon
      therapy, serum TGF-beta was significantly higher in the burn patients with
      hypertrophic scarring than in a control population (123.04 +/- 36.48 vs. 56.85 +/
      8.38 ng/ml, p < 0.05). Within 3 months of IFN alpha-2b therapy, serum TGF-beta
      levels fell significantly and remained within the normal range during therapy and
      after interferon therapy was stopped. Plasma Ntau-methylhistamine levels were
      also significantly elevated in the hypertrophic scar patients as compared with
      age and sex-matched controls (153.6 +/- 92.07 vs. 48.3 +/- 28.9 pg/ml, p < 0.05),
      and significant reductions were achieved with interferon therapy and maintained
      after interferon was discontinued. Paired biopsies of hypertrophic scarring and
      normal tissue demonstrated increased numbers of mast cells in hypertrophic scars
      compared with normal uninjured skin from the same patients (2.65 +/- 1.63 vs.
      1.04 +/- 0.62 cells/high power field, p < 0.001); however, no significant change
      in mast cell content of the hypertrophic scars accompanied interferon therapy.
      Patients with severe hypertrophic scarring demonstrate increased levels of serum
      TGF-beta and plasma Ntau-methylhistamine following thermal injury. A significant
      clinical improvement in scar quality and volume occurred during IFN alpha-2b
      therapy, which was associated with normalization of serum TGF-beta and plasma
      Ntau-methylhistamine levels. A double-blind, placebo-controlled trial will be
      required to further assess the usefulness of subcutaneous treatment with IFN
      alpha-2b for the treatment of hypertrophic scarring.

PMID- 9773989
TI  - Nasal sill augmentation in adult incomplete cleft lip nose deformity using
      superiorly based turn over orbicularis oris muscle flap: an anatomic approach.
AB  - Adult incomplete cleft lip nose deformity is not uncommon in India. Poverty,
      ignorance, and parental neglect account for its late presentation. Besides the
      classical features of cleft lip nose deformity, the constant findings observed in
      this patient population have been a widened and depressed nasal sill. This is
      attributable to the sparse, hypoplastic, and abnormally orientated orbicularis
      oris muscle in the region of the sill. Failure to restore the nasal sill symmetry
      by suitably augmenting the sill frequently leads to unsatisfactory and asymmetric
      results. However, in the literature, satisfactory restoration of the nasal sill
      has not been given the importance it deserves while performing cleft lip
      rhinoplasty. We present a method of augmenting the depressed nasal sill in cases
      of adult incomplete nose deformity using a superiorly based orbicularis oris
      muscle flap, which is harvested from the soft tissues between the apex of the
      cleft and the nostril sill. Following de-epithelialization of the overlying skin,
      the exposed muscle is raised as a superiorly based flap after dissecting it from
      the underlying mucosa. It is folded, turned over, and tucked into the nasal sill
      base and anchored to the anterior nasal spine to give the desired augmentation.
      Satisfactory results have been obtained in 18 cases of nasal deformity associated
      with incomplete cleft lip. In our opinion, this technique offers a simple and
      effective method of augmenting the depressed sill by utilizing locally available
      tissues and without the need for procuring autologous tissue from distant sites.

PMID- 9773988
TI  - Photogrammetric comparison of two methods for synchronous repair of bilateral
      cleft lip and nasal deformity.
AB  - The principle of synchronous repair of bilateral complete cleft lip and nasal
      deformity is established, and the techniques are evolving. We undertook
      photogrammetric comparison of the method described by Mulliken (group I, n = 15)
      and that described by Trott (group II, n = 10). Facial proportions and angles
      were measured on preoperative and postoperative photographs using defined
      anthropometric points. The following criteria were quantified for each test
      group: nasolabial angle, nasal tip angle and projection, nasal width, columellar
      length and width, and philtral width. All parameters in both groups were compared
      against each other and against normal age-matched values. Results were analyzed
      by t test. The nasolabial angle, nasal tip angle, and nasal width were abnormally
      wide for both techniques (p < 0.01 for both), and there was no difference between
      them. Nasal tip projection was greater than normal in both techniques (p < 0.01);
      group I had significantly greater projection than group II (p = 0.02). Columellar
      length as a proportion of nasal tip protrusion approached normal in group I but
      was significantly shorter than normal in group II (p < 0.001). Columellar width,
      as a proportion of nasal width, was normal for both groups. Philtral width, in
      proportion to nasal width, was normal in group I and abnormally high in group II
      (p < 0.001). This difference was significant between the two groups (p < 0.001).
      In a separate cohort of 10 group I patients, the nasolabial angle was measured on
      lateral photographs taken 1 year post-repair and at intervals to late childhood
      and adolescence. Nasolabial angle changed with age from obtuse to normal in 7 of
      10 patients followed to 9 years of age and in 5 of 6 patients followed until age
      15 years. Columellar and upper labial inclination to the vertical were measured
      in 7 of these patients at 3 to 4 years and again at 13 to 15 years. There was an
      increase in inclination of both columella and the upper lip, between the ages of
      3 to 4 and 13 to 15 years, reflecting improved lip support and growth of septum
      and lateral cartilages.

PMID- 9773990
TI  - Rigid external distraction: its application in cleft maxillary deformities.
AB  - Patients with severe maxillary hypoplasia secondary to congenital facial clefting
      present numerous challenging problems for the reconstructive surgeon. Traditional
      surgical/orthodontic approaches for these patients often fall short of
      expectations, especially for achieving normal facial aesthetics and proportions.
      The purpose of this paper is to present our clinical experience and cephalometric
      results with the use of rigid external distraction for the treatment of patients
      with severe maxillary deficiency. Eighteen consecutive orofacial cleft patients
      with severe maxillary hypoplasia were treated with maxillary distraction
      osteogenesis. Criteria for patient selection included severe maxillary hypoplasia
      with negative overjet of 8 mm or greater, patients with normal mandibular
      morphology, and patients with full primary dentition or older. There were 10
      unilateral cleft lip and palate patients, 6 bilateral cleft lip and palate
      patients, and 2 patients with severe congenital facial clefting. A maxillary
      splint was prepared for each patient, and all patients underwent a high Le Fort I
      maxillary osteotomy. All surgery was performed on either an outpatient or a 23
      hour admission basis. No patient required blood transfusions or intermaxillary
      fixation. Two types of mechanical distraction were utilized in this series. In
      group 1 (n = 14), the patients underwent rigid external distraction with an
      external distraction device. In group 2 (n = 4), patients underwent face mask
      distraction with elastics. There was no surgical morbidity in any of the
      patients. For the patients in the rigid external distraction group, the mean
      effective horizontal advancement of the maxilla was 11.7 mm. All of these
      patients had correction of their negative overjet. For patients in the face mask
      distraction group, the results were disappointing. The mean effective advancement
      of the maxilla in this group was only 5.2 mm. In all face mask distraction
      patients, the initial maxillary hypoplasia was undercorrected. Maxillary
      distraction osteogenesis with rigid external distraction permits full correction
      of the midfacial deficiency, including both the skeletal and soft-tissue
      deficiencies. Rigid external distraction in patients with severe maxillary
      hypoplasia allows full correction of the deformity through treatment of the
      affected region only. It offers the distinct advantage of correcting these severe
      deformities through a minimal procedure. Rigid external distraction has
      dramatically improved our treatment results for patients with severe cleft
      maxillary hypoplasia.

PMID- 9773991
TI  - The effect of surgeon experience on velopharyngeal functional outcome following
      palatoplasty: is there a learning curve?
AB  - There is little information in the cleft palate literature concerning the
      relationship between surgeon volume and clinical outcomes. It is unknown whether
      such a relationship applies specifically to velopharyngeal dysfunction and the
      need for secondary physical management of the velopharynx. The purpose of this
      paper was to explore the concept of an operative learning curve for different
      surgeons with respect to palatoplasty. Impact of case volume and procedure type
      on the occurrence of secondary palatal management (the main outcome measure) was
      assessed. The charts of 472 consecutive palatoplasty patients were reviewed by
      one speech and language pathologist to determine when the palatoplasty was
      performed, which surgeon (n = 9) performed the palatoplasty, whether
      velopharyngeal status was documented at a minimum of 6 years of age, and whether
      secondary palatal management was prescribed. The results were analyzed by year of
      palatoplasty, by surgeon, and by number of operations per surgeon to determine
      total and individual surgeon rates of secondary palatal management. There were
      401 palatoplasties (85 percent recovery) with adequate documentation of
      velopharyngeal status by at least 6 years of age. Palatoplasty rates ranged
      between 1 and 258 palatoplasties per surgeon. Over the 12 years reviewed,
      secondary palatal management was performed for 92 patients (23 percent) of the
      study population. Examination of the proportion of palatoplasty patients
      receiving secondary palatal management by surgeon and by year showed only one
      surgeon with a pattern suggesting a learning curve. The proportion of patients
      receiving secondary palatal management was plotted against the total number of
      surgeries the surgeon performed. There was a strong relationship between
      experience and success. The number of procedures this surgeon performed per year
      increased at approximately the same time as the success rate improved. The
      categories of "total procedures" and "procedure per year" were highly correlated
      with each other. Success rates were analyzed by number of procedures performed
      per year, and there was a clear association between the two variables. To
      separate the effect of the two variables, a multiple regression model was
      constructed. The category of "total procedures" was statistically significant in
      the model, whereas procedures per year was not, suggesting that the key to the
      dominant surgeon's improvement was cumulative experience rather than frequency of
      performance of the operation. Palatoplasties performed by high-volume surgeons
      are more likely to result in better postoperative outcomes (i.e., lower rates of
      secondary palatal management) as compared with palatoplasties performed by low
      volume surgeons. The influence of the surgeon's cumulative experience on
      improvement seems to be more important than the frequency of performance of
      primary palatoplasty.

PMID- 9773992
TI  - Investigation of the influences of biomechanical force on the ultrastructure of
      human sagittal craniosynostosis.
AB  - This study presents comparisons of the ultrastructure of synostotic and open
      portions of synostotic sagittal sutures using histomorphometry, scanning electron
      microscopy, and microcomputed tomography. By using stereologic and
      histomorphometric analysis, this study proposes to demonstrate evidence of the
      influence of biomechanical force on the suture during the process of sagittal
      craniosynostosis. Finally, we propose to link the pathologic changes transforming
      normal suture fusion to craniosynostosis with concurrent changes in the polarity
      of suture fusion initiation. Seven infants (four boys and three girls) with
      sagittal craniosynostosis, ranging in age from 1.4 to 4.8 months (mean = 3.0
      months), underwent sagittal synostectomies. The synostotic bone specimens were
      sectioned into three regions: an open suture, partial synostosis, and complete
      synostosis. Microcomputed tomographic and scanning electron microscopic scanning
      as well as histomorphometry was performed on all specimens to obtain detailed
      qualitative and quantitative information regarding the trabecular
      microarchitecture of the synostosed suture. Microcomputed tomographic analysis
      determined the bone volume fraction, trabecular thickness, trabecular separation,
      bone surface to bone volume ratio, and anisotropy for all specimens. Our results
      showed significant differences in all of these quantitative measurements when
      comparing the complete synostotic suture with the open portion of the synostotic
      sutures (p < 0.05). Microcomputed tomographic stereologic analysis showed
      evidence of the influence of biomechanical force on the synostotic and open
      portions of the synostotic sutures. Results of scanning electron microscopy show
      a definite qualitative difference in the trabecular pattern of the partial and
      complete synostotic suture when compared with the open portion of the synostotic
      sagittal suture. In this study, we performed both qualitative and quantitative
      comparisons of the ultrastructure of the complete synostotic and nonsynostotic
      sagittal sutures using stereologic and histomorphometric techniques. We also
      demonstrated evidence of the influence of biomechanical force on the synostotic
      sagittal suture. Finally, we established a link between the pathologic changes
      transforming normal suture fusion to craniosynostosis and concurrent changes in
      both the vector and direction of suture fusion initiation.

PMID- 9773993
TI  - Presurgical finite element analysis from routine computed tomography studies for
      craniofacial distraction: II. An engineering prediction model for gradual
      correction of asymmetric skull deformities.
AB  - Finite element analysis from routine computed tomography studies (CT/FEA) allows
      clinicians to predict the mechanical and anatomic consequences of specific
      distraction systems before human application. A realistic three-dimensional
      CT/FEA engineering model of an actual plagiocephalic infant with unicoronal
      synostosis was developed using 4215 parabolic triangular shell elements and
      intracranial pressure conditions ranging from 10 to 20 mmHg. The completed finite
      element analysis model was used to predict the anatomic outcome of multiaxial
      distraction delivered by hypothetical patterns of rod and node distraction units.
      The predictions for the various patterns of distraction units were also compared
      quantitatively with respect to force, stress, strain, and intracranial volume.
      Best anatomic corrections were achieved with bilateral patterns of distraction
      units that simultaneously elongated the ipsilateral cranium and shortened the
      contralateral cranium. Greatest strain levels were experienced within the
      osteotomy callus, greatest stress levels at the appliance anchorage sites, and
      the greatest rod force at the ipsilateral lower coronal position.

PMID- 9773994
TI  - The excised preauricular sinus in 14 years of experience: is there a problem?
AB  - The congenital preauricular sinus is usually asymptomatic. However, if recurrent
      infection occurs, complete surgical excision of the sinus is required. If the
      sinus tracts are not entirely removed, recurrence is likely to follow. A
      retrospective study of the surgical results at The Hospital for Sick Children in
      Toronto, Ontario, was completed. One-hundred sixty-five primary preauricular
      excision procedures, performed in 146 patients between the years 1982 and 1996,
      were reviewed. All clinical, operative, and postoperative data were gathered.
      Patient outcome and epidemiologic issues were addressed. The overall recurrence
      rate of this series was 9.09 percent (15 of 165 sinuses). For the group of
      patients with active infection present at surgery, the recurrence rate was 15.79
      percent, and when no infection was present, recurrence rate was 8.22 percent (p
      value = 0.32, odds ratio = 2.09). Moreover, in patients who underwent surgical
      drainage of an abscess before the procedure, 16.7 percent of the sinuses
      recurred, whereas in the patients who did not have an abscess, only 8.16 percent
      recurred (p value = 0.25, odds ratio = 2.25). In the group of patients in whom
      auricular cartilage was not excised from the base of the tract, 18.52 percent of
      the sinuses recurred; when cartilage was excised, the recurrence rate was 4.5
      percent (p value = 0.006). A very high recurrence rate of 21.95 percent was found
      in the group of patients in whom no modality was used to demonstrate the sinus
      tract at surgery. A high recurrence rate of 10.87 percent was found in the group
      for whom probing with a cannula was used to identify the tract (p value = 0.17);
      a low recurrence rate of 2 percent was found in a group with dye injection only
      (p value = 0.015). In those patients in whom sinus probing and dye injection were
      used simultaneously, there were no recurrences (0 percent, p value < 0.05). In
      conclusion, a patient with an actively infected preauricular sinus or one with a
      previous abscess may have a tendency to experience a higher recurrence rate after
      excisional surgery. Excising a cartilage piece at the base of the tract and
      demonstrating the sinus with dye injection or with dye injection and probing at
      the time of surgery will reduce recurrence rates. In conclusion, we advise the
      excision of cartilage in the base of the tract as well as the use of methylene
      blue injection and probing of the sinus at surgery.

PMID- 9773995
TI  - Blindness as a complication of Le Fort osteotomies: role of atypical fracture
      patterns and distortion of the optic canal.
AB  - Blindness in patients suffering maxillofacial trauma is usually caused by optic
      nerve or optic canal injuries. It is, however, an uncommon complication of facial
      trauma, with a reported incidence of only 3 to 5 percent. This incidence drops
      dramatically when fractures are performed in the controlled situation of
      orthognathic surgery. Given the rarity of ophthalmic complications after
      traumatic Le Fort I injuries, it is not surprising that few cases have been
      reported after orthognathic surgery. In this article, three cases of visual loss
      or skull base injury after elective Le Fort I osteotomy are described. All of
      these cases were presumably straightforward surgically and were performed by
      experienced surgeons. The literature is reviewed and the pathomechanics of each
      injury are experimentally explored in a cadaver model. To determine the presence
      of increased pressure on the optic nerve, optic canal deformation, or fractures
      extending to the skull base, two separate experiments were devised. In the first
      experiment, a pressure transduction system was used to document any significant
      forces that may be directly transmitted to the contents of the optic canal during
      pterygomaxillary separation. Then tested was the hypothesis that a stepped or
      tapered osteotomy will allow for a more predictable pterygomaxillary fracture.
      One of five cadaver specimens in group 1 demonstrated a transient increase in the
      right optic canal pressure during down-fracture of the maxilla. This change was
      less than 10 mmHg, and its duration was less than 5 seconds. The canal pressure
      returned to baseline with the completion of the fracture. In group 2, there was
      no documented pressure change with either osteotomy technique. Of note, in group
      2, all specimens undergoing standard Le Fort osteotomy demonstrated uncontrolled
      propagation of the fracture lines superiorly in the pterygoid bones. The
      uncontrolled and unpredictable nature of pterygomaxillary disjunction may result
      in the extension of fractures to the skull base or the generation of deforming
      forces to the optic canal may compress or injure the optic nerve and its
      circulation. It is proposed that a stepped or tapered osteotomy will generate a
      more controlled pterygomaxillary separation during orthognathic surgery and may
      reduce the risk of devastating ophthalmologic complications.

PMID- 9773996
TI  - Facial reconstruction with local and distant tissue: the interface of aesthetic
      and reconstructive surgery.
AB  - The difficulty of facial reconstruction derives from the unique character of the
      face and the availability of local matching tissues. By necessity, distant free
      flaps have become a first choice for large, complicated facial wounds.
      Unfortunately, although the wound can be closed, distant tissue does not match
      facial skin in color, texture, or thickness or have a facial shape. Distant skin
      always appears as a mismatched patch within residual normal facial skin. In
      contrast, the subunit approach to reconstruction, employing local tissue,
      emphasizes the restoration of facial units--adjacent topographic areas of
      characteristic skin quality, outline, and contour that describe a normal face and
      define the desired end result. These subunit principles help hide scars, maintain
      facial skin quality, and restore contour and landmark symmetry. Over several
      years the principles of subunit reconstruction and microvascular surgery have
      been applied to the "difficult" facial defect to incorporate both local and
      distant tissue into an aesthetic facial reconstruction. By combining the two
      approaches, the reconstruction of a massive facial defect can be taken to its
      logical conclusion: a functionally and aesthetically rehabilitated patient. The
      reconstruction of a massive facial defect should have two stages. Initially,
      distant tissue should be supplied to the complicated facial defect to supply
      bulk, protect vital structures, revascularize the wound, and reconstruct a stable
      facial platform. At later stages, subunit principles must be applied to restore
      facial skin quality, outline, and contour. Local tissue is used for aesthetic
      cover and distant tissue for the "invisible" requirements (lining and support)
      but not to replace surface skin. Conventional techniques and local grafts and
      flaps are employed to contour facial units and resurface individual regions.

PMID- 9773997
TI  - Endoscopic subcondylar fracture repair: functional, aesthetic, and radiographic
      outcomes.
AB  - An endoscopic method of mandibular subcondylar fracture repair has been described
      recently. To determine the effectiveness of this new technique, we longitudinally
      studied functional, aesthetic, and radiographic parameters following endoscopic
      repair of 22 subcondylar fractures in 20 patients. Restoration of mandibular
      function was achieved without postoperative maxillomandibular fixation. Premorbid
      occlusion was restored. Clinical jaw motion was found to progressively increase
      with a mean interincisal jaw opening of 43 mm achieved after the eighth
      postoperative week. Patients were pleased with the aesthetic restoration of their
      chin projection,jaw line, and the symmetric midline movement of the chin point
      onjaw opening. Anatomic fracture reduction with rigid plate fixation was
      confirmed on early postsurgical radiographs. Late radiographs showed fracture
      union without remodeling of the condylar head. Endoscopic subcondylar fracture
      repair was efficacious at functional, aesthetic, and radiographic restoration of
      the mandible.

PMID- 9773998
TI  - Applications of endoscopic surgery in pediatric patients.
AB  - Although the advent of endoscopic technology is expanding the fields of
      reconstructive and aesthetic surgery in adults, there have been few reports of
      the use of this technology in the pediatric population. Because of their
      minimally invasive nature, yet wide range of exposure, endoscopic techniques have
      much appeal for this age group. Here we present our experience with endoscopic
      pediatric plastic surgery. From February of 1995 to August of 1997, 104 patients
      underwent 139 procedures utilizing 5- and 10-mm endoscopes. There were 58 male
      and 46 female patients. The mean age at surgery was 5.6 years (range, 3 weeks to
      19 years). The most common type of procedures performed were insertion of tissue
      expanders (n = 34), excision of benign head and neck masses (n = 27), torticollis
      release (n = 20), excision of vascular lesions (n = 13), and miscellaneous
      procedures, (n = 10). There were 26 complications in 139 procedures (19 percent).
      Seventeen (65 percent) were in the tissue expander group. The rest were scattered
      among the groups with other diagnoses. Although there did not appear to be a
      specific type of complication associated with endoscopy, 77 percent occurred in
      the first 2 months of our study. This suggests a relatively steep technical
      learning curve. These results demonstrate that endoscopic techniques are
      eminently applicable in the pediatric population, providing the benefits of small
      and remote incisional wounds, with complication rates that are comparable with
      those of conventional open surgical treatment.

PMID- 9773999
TI  - Breast reconstruction by means of innervated rectus abdominis myocutaneous flap.
AB  - We performed immediate breast reconstruction in 22 patients using rectus
      abdominis myocutaneous flap accompanied by neurorrhaphy in the past 2 years. In
      the neurorrhaphy, the 11th intercostal nerve, which controls the sensation of the
      myocutaneous flap, was anastomosed to the lateral cutaneous branch of the 4th
      intercostal nerve, which controls the sensation of the breast. Our study included
      15 patients, and the postoperative follow-up period was 4 to 24 months, with an
      average of 14.0 months. For control subjects, there were 16 cases of rectus
      abdominis myocutaneous flap, whose sensory nerve had not been reconstructed
      (postoperative follow-up period 11 to 41 months, average 24.1 months). The
      sensory examination included tests of touch, pain, and temperature. The
      innervated myocutaneous flap sensation showed gradual recovery at about 6 months
      after surgery and reached the value of the normal side after about 1 year. In the
      control subjects, recovery of sensation was not observed at all in the first 10
      postoperative months. Then, after more than 1 year, the recovery was gradual and
      reached the value of the normal side in only some control subjects. Therefore, we
      consider the present technique useful for recovery of sensation in immediate
      breast reconstruction.

PMID- 9774000
TI  - Autologous latissimus breast reconstruction: a 3-year clinical experience with
      100 patients.
AB  - This article presents our technique of autologous breast reconstruction using the
      latissimus dorsi flap and studies the advantages, disadvantages, and results that
      can be expected. A consecutive sample of 100 patients was studied. The average
      length of follow-up was 20 months (range 8 to 44 months), and all of the subjects
      were reviewed in consultation without loss to follow-up. The supplementary volume
      of the latissimus dorsi was obtained from five fatty zones: fat on the cutaneous
      paddle, fat taken from the surface of the muscle, the scapular fat pad, the
      anterior fatty zone, and the supra-iliac fat pad. This technique must be measured
      against the transverse rectus abdominis muscle (TRAM) flap, free or pedicled,
      when the patient needs an autologous breast reconstruction. It can be used when
      the TRAM flap is contraindicated (this corresponds to 45 percent of patients of
      our sample) or when the dorsal donor site is preferred (55 percent of cases of
      our sample). The major complications are rare (1 percent partial necrosis and 1
      percent total necrosis of the flap). The minor complications are represented
      mainly by the dorsal seroma. This is the main drawback of the technique, as it
      occurs in 79 percent of cases and regularly in obese patients. In view of this
      frequency, patients should be warned of its likely occurrence. The dorsal donor
      site morbidity is relatively low; 4 percent of dorsal sequelae were classed as
      moderate, and 96 percent were considered low. The scapular sequelae have been
      classed as low in 97 percent of cases, and temporary scapular sequelae
      aggravation has been noted in 3 percent. Results of breast reconstruction using
      this technique are most encouraging. The level of patient satisfaction is high;
      87 percent of them were deeply satisfied, 10 percent were satisfied, and only 3
      percent were poorly satisfied. This group of poorly satisfied subjects (3
      percent) consists of patients who suffered a serious postoperative complication.
      The aesthetic results have been judged excellent by surgeons in 85 percent of the
      cases, good in 12 percent of the cases, and poor in 3 percent of the cases; no
      result has been judged bad. This technique of breast reconstruction by autologous
      latissimus dorsi brings a major advance in breast reconstruction. The best
      indications of this technique are when one can bury the cutaneous paddle: cases
      of skin-sparing mastectomy, cases where the latissimus dorsi flap can be combined
      with an abdominal advancement flap, and cases of conversion of implant
      reconstruction to an autologous reconstruction.

PMID- 9774001
TI  - Treatment of axillary bromhidrosis with superficial liposuction.
AB  - Axillary bromhidrosis or osmidrosis is a distressing problem that causes a
      serious personal and social handicap, especially in an Asian society. Surgical
      excision of the subcutaneous tissue, with or without skin excision in the
      axillary hair-bearing area, has been the treatment of choice for several decades.
      However, the complications of partial necrosis of wound edges or hematoma, and
      the possibility of the obvious unsightly scars, are always problems. We report
      our method of treatment of modified superficial liposuction with subdermal
      scraping under local anesthesia with tumescent infiltration. By using two tiny
      stab wounds, these two steps of liposuction can be done in the two-directional
      crisscross pattern. From August of 1995 to May of 1997, 20 patients (16 women and
      4 men) received this surgery for bilateral axillas on an outpatient basis. The
      follow-up period ranged from 6 months to 27 months, and the mean follow-up period
      was 14 months. Eighteen patients (90 percent) had excellent to good results.
      Complication included only one minor wound infection that was cured easily. Two
      patients experienced transient subdermal fibrotic bands in one side of the
      axilla, and one patient experienced axillary skin with marked induration and
      retraction. All of these symptoms disappeared after 1 month or so. This minimal
      incision operation has the advantages of a high success rate, low complication
      rate, tiny to invisible scars, no change of hair distribution pattern, minimal
      postoperative care with a short term of compressive dressing (less than 2 days),
      and rapid recovery for daily activity and exercise.

PMID- 9774002
TI  - Staged skin and subcutaneous excision for lymphedema: a favorable report of long
      term results.
AB  - Numerous surgical procedures have been proposed for the management of lymphedema.
      The postoperative results vary, and unfortunately none of the procedures are
      curative. As a result, some degree of recurrence of leg edema is seen in all
      patients postoperatively. Reported here is a long-term follow-up of patients with
      lower extremity lymphedema managed by skin and subcutaneous tissue excision.
      Thirty-eight patients (6 male; 32 female) with lower extremity lymphedema have
      been followed up for an average of 14 (3 to 27) years after staged subcutaneous
      excisions performed beneath skin flaps. Seven patients had been treated
      previously by other procedures. Of the 38 lymphedema patients, 10 patients
      developed edema after pelvic or groin ablative surgery, radiation therapy, or
      both. Results were documented by various methods: physical examination,
      circumferential measurements, volume displacement, serial photography,
      lymphoscintigraphy, and patient survey. Of these, it is believed that photographs
      are the easiest and as representative as any other method, all of which have
      great variability. Of the 38 patients, 30 patients had significant and long
      lasting reduction in extremity size associated with improved function and
      extremity contour. Episodes of recurrent cellulitis were reduced or completely
      eliminated. No differences in the long-term results were seen in patients with
      acquired as opposed to congenital lymphedema. Men did not have as much
      improvement as women. Two patients had no change in leg swelling, and six
      patients (three men) had progressive swelling after surgery. Partial wound
      separation occurred immediately postoperatively in one patient, and three
      patients had loss (less than 2 cm) of the skin flap, all in the ankle region.
      None of these instances required further surgery, and no other significant
      complications were encountered. Staged skin and subcutaneous excision beneath
      skin flaps appears to provide long-lasting improvement for lower extremity
      lymphedema, regardless of cause, in the majority of patients treated.

PMID- 9774003
TI  - Fat necrosis in free and pedicled TRAM flaps.
AB  - One purported advantage of the free transverse rectus abdominis musculocutaneous
      (TRAM) flap for breast reconstruction is that, compared with the conventional
      TRAM flap, it has a better blood supply and therefore a lower incidence of fat
      necrosis. We tested this claim by reviewing the incidence of fat necrosis, both
      clinically and mammographically, in a group of 110 patients with 116 TRAM flap
      breast reconstructions who had undergone mammography of their reconstructed
      breasts. Of the 49 breasts reconstructed with free TRAM flaps, 4 (8.2 percent)
      had clinically evident fat necrosis, and 1 (2.0 percent) had fat necrosis that
      was detectable by mammography. Of the 67 breasts reconstructed with conventional
      TRAM flaps, 18 (26.9 percent) had clinically detectable fat necrosis, and 9 (13.4
      percent) had fat necrosis that was detectable mammographically. Both of these
      differences were statistically significant (p = 0.0113 for clinical fat necrosis;
      p = 0.031 for mammographic fat necrosis). Fat necrosis was more common in
      patients who were obese or had a history of smoking, but neither association was
      statistically significant. We conclude that the use of the free TRAM flap reduces
      the incidence of fat necrosis in the reconstructed breast.

PMID- 9774004
TI  - Donor-site morbidity after pedicled or free TRAM flap surgery: a prospective and
      objective study.
AB  - The main disadvantage when the transverse rectus abdominis musculocutaneous
      (TRAM) flap is used for breast reconstruction is the potential for weakening of
      the abdominal wall. This prospective study was initiated to objectively evaluate
      abdominal muscle strength after pedicled and free TRAM flap breast
      reconstructions over time. Twenty-three patients with pedicled TRAM flaps and 19
      patients with free TRAM flaps were included. A dynamic dynamometer system, KIN
      COM, was used to measure maximal voluntary trunk flexor and extensor strength
      preoperatively and 6 and 12 months postoperatively. The patients' subjective
      opinions 1 year postoperatively were recorded by means of a questionnaire. A
      transient decrease in abdominal strength, in both groups, occurred at 6 months
      but was essentially regained at 12 months. The use of a pedicled or free TRAM
      flap did not influence postoperative abdominal strength per se. The balance
      between the abdominal strength and back strength remained in the free flap group
      but was altered postoperatively in the pedicled flap group; back strength was
      increased and remained so after 12 months. The difference between the two
      procedures is relatively small compared with individual variations, indicating
      that there are more important factors than the kind of surgery influencing the
      restoration of muscle strength. The questionnaire revealed a greater occurrence
      of abdominal wall bulging in the free flap group (82 percent) versus 48 percent
      in the pedicled flap group. No postoperative differences regarding exercise
      frequency or sensitivity of the abdominal wall were found between the pedicled
      and free TRAM flap groups.

PMID- 9774006
TI  - Island V-Y tensor fasciae latae fasciocutaneous flap for coverage of trochanteric
      pressure sores.
AB  - The distal fasciocutaneous portion of the lateral thigh is supplied by the direct
      cutaneous branch of the lateral descending branch of the lateral circumflex
      femoral artery and the third perforating artery of the deep femoral artery. This
      consistent vascular anatomy allows raising a distal skin island based on both
      arteries on the lateral thigh, and this flap can be advanced into a trochanteric
      defect according to the V-Y technique. Based on anatomic and clinical study, a
      new design has been developed of the tensor fasciae latae fasciocutaneous flap,
      which is supplied by two pedicles. Seven island V-Y tensor fasciae latae
      fasciocutaneous flaps have been used for the coverage of trochanteric pressure
      sores in six patients. It is believed that the island V-Y tensor fasciae latae
      fasciocutaneous flap could overcome the traditional drawbacks of the conventional
      tensor fasciae latae flap and its modifications, and this is an ideal flap for
      covering trochanteric pressure sores without any donor site deformity and
      morbidity, which greatly improves the aesthetic result.

PMID- 9774005
TI  - Anatomic variations and technical problems of the anterolateral thigh flap: a
      report of 74 cases.
AB  - We have transferred 74 free or pedicled anterolateral thigh flaps, including
      those combined with other flaps, for reconstruction of various types of defects.
      We report several anatomic variations of the lateral circumflex arterial system
      and discuss some technical problems with this flap. Septocutaneous perforators
      were found in 28 of 74 cases (37.8 percent), and no perforators were found in 4
      cases (5.4 percent). In the 70 cases with perforators, 171 tiny cutaneous
      perforators (an average of 2.31 per case) were found. Musculocutaneous
      perforators (81.9 percent) were much more common than septocutaneous perforators
      (18.1 percent). Perforators were concentrated near the midpoint of the lateral
      thigh, and the selection of perforators as nutrient vessels for the anterolateral
      thigh flap was related to the length of the pedicle and the thickness of the skin
      flap. Anatomic variations of the branching pattern of perforators were classified
      into eight types. Flaps with perforators that arise directly from the profunda
      femoris artery are difficult to combine with other free flaps. Because the
      perforators are extremely small and tend to thrombose soon after congestion
      develops, these flaps are difficult to salvage with recirculation surgery.
      Therefore, several perforators should be included with the flap, if possible. The
      descending artery of the lateral circumflex femoral artery was always accompanied
      by two veins with different back-flow strengths. Therefore, veins for
      microsurgical anastomosis must be chosen carefully. Because it is nourished by
      several perforators arising from the descending artery, the vastus lateralis
      muscle can be combined with the anterolateral thigh flap. However, splitting the
      muscle longitudinally without harvesting its blood supply is complicated because
      its fibers are oblique. The rectus femoris muscle can also be combined with the
      anterolateral thigh flap, but its pedicle is short and its origin is very near
      the site of anastomosis. When the anterolateral thigh flap is combined with the
      tensor fasciae latae musculocutaneous flap, the large skin area of the lateral
      part of thigh can be transferred to repair the massive defects. The anterolateral
      thigh flap has many advantages and can be used to reconstruct many types of
      defect. However, anatomic variations must be considered if the flap is to be used
      safely and reliably.

PMID- 9774007
TI  - Clinical application of expanded free flaps based on primary or secondary
      vascularization.
AB  - Prefabricated free flaps using an expansion technique were used for four
      reconstructive cases, including two leg reconstructions and two facial
      reconstructions. In this series, the prefabricated free flaps created by using
      the expander were classified into two types: the expanded flap based on the
      conventional vascular pedicle, which is called the expanded flap with primary
      vascularization; and the expanded flap based on the vascular pedicle in the
      carrier, which is called the expanded flap with secondary vascularization. The
      expanded flap with primary vascularization that is created in the trunk has a
      good indication for leg reconstruction, because it provides an wide and thin flap
      with minimal donor site morbidity. The expanded flap with secondary
      vascularization created in the pectoral region has a good indication for facial
      reconstruction, because it provides good color and texture matches. Although
      there are some disadvantages in the tissue expansion technique, the prefabricated
      free flaps using the expander are very effective in facial and leg
      reconstruction.

PMID- 9774008
TI  - Cutaneous hemoglobin oxygenation of different free flap donor sites.
AB  - Microsurgical skin flaps raised from various body regions show differences in
      vascular architecture, cutaneous capillary density, and skin perfusion.
      Therefore, it can be expected that oxygenation of the skin is different at the
      various free flap donor sites. To determine the cutaneous oxygen supply,
      intracapillary hemoglobin oxygenation was measured on the donor sites of the
      radial forearm flap, scapula, latissimus dorsi, rectus abdominis, anterolateral
      thigh, and osteocutaneous fibula flap on 50 healthy subjects (25 men and 25 women
      aged 20 to 40 years). Measurements were performed noninvasively with the Erlangen
      Microlightguide Spectrophotometer (EMPHO) on skin areas of 6 x 8 cm in each
      region under resting conditions. The hemoglobin oxygenation of the skin in all
      donor regions varied between a maximum of 43.94 to 58.94 percent in the scapula
      region and a minimum of 13.89 to 29.45 percent in the lateral calf. High
      oxygenation values were also found on the skin over the latissimus dorsi muscle
      (34.56 to 48.45 percent), followed by the distal volar forearm (29.78 to 40.30
      percent), whereas paraumbilical skin and the donor sites of the lower extremities
      were less oxygenated. By using the Wilcoxon test, significant differences were
      found between all donor regions except for the anterolateral thigh and lateral
      calf (p = 0.05). There were no gender-specific differences. From these results,
      it is concluded that, on young healthy subjects, regional oxygen supply on
      different free flap donor sites varies significantly. This finding must be
      considered in the interpretation of intracutaneous or transcutaneous PO2
      measurements for flap monitoring.

PMID- 9774009
TI  - Reliability of the venae comitantes in venous drainage of the free radial forearm
      flaps.
AB  - The radial venae comitantes are usually considered as an accessory venous outflow
      tract in the free radial forearm flap because of their smaller size and thinner
      structure when compared with those of the cephalic vein. To evaluate the
      reliability of the deep venous system, a single radial vena comitans anastomosis
      was performed to serve as the sole venous outflow tract in 94 consecutive radial
      forearm free flap transfers. The suprafascial dissection technique was used in
      flap elevation, which allowed preservation of the cephalic vein and the dorsal
      branch of the radial nerve. In all cases, the external diameter of at least one
      vena comitans was adequate (< or = 1.5 mm) to perform a smooth microvascular
      anastomosis; in none of the cases was a venous anastomosis failure detected.
      Preselected use of a single vena comitans for the venous drainage of radial
      forearm free flaps was proven to be reliable and was preferred because of the
      ease of flap dissection and better donor site appearance.

PMID- 9774010
TI  - Dorsalis pedis flap donor site: acceptable or not?
AB  - The dorsalis pedis flap has been used successfully for 20 years, both as a
      pedicled transfer for local foot reconstruction and as a free microvascular
      transfer. Proponents cite the reliable vascularity, versatility, ease of harvest,
      and thinness. Although significant donor-site morbidity has been recognized
      previously, published reports have inadequately documented the long-term effects
      of dorsalis pedis flap harvest. The purpose of the present study was to obtain
      long-term follow-up data regarding the donor site on a total of 10 male patients
      who underwent dorsalis pedis flap harvest during the period from 1982 to 1984.
      Standardized questionnaires and chart reviews were completed, and physical
      examinations and photographs of each patient were carried out when possible.
      Eight patients were reviewed, and seven of them were examined and photographed
      (mean follow-up 13 years). All patients had initially experienced delayed donor
      site healing (mean 18 months; range 3 to 36 months). In addition, soft-tissue
      infections (five of eight cases), osteomyelitis (one of eight cases), wound
      breakdown (seven of eight cases), scarring and contracture (four of seven cases),
      pain or other uncomfortable sensations in the foot (six of seven cases), and
      requirement for reoperation (three of eight cases) were significant complications
      of the procedure. Most patients were able to attain their preoperative level of
      physical activity (five of eight cases). Although generally favorable
      reconstructive results were obtained in this series, the long-term follow-up of
      donor-site healing indicates that this flap should be used with caution. In
      particular, delayed donor-site healing, need for wound revision, and long-term
      and possibly permanent donor-site symptoms are common.

PMID- 9774011
TI  - Neuroma-in-continuity resection: early outcome in obstetrical brachial plexus
      palsy.
AB  - The short-term effect of neuroma-in-continuity resection in obstetrical brachial
      plexus palsy was evaluated to test the hypothesis that the neuroma does not
      contribute to useful limb function. Twenty-six patients with obstetrical brachial
      plexus palsy underwent resection of the neuroma-in-continuity and interpositional
      nerve grafting, and 17 patients underwent neurolysis only. The preoperative and
      postoperative active movement scores were recorded using an eight-point scale for
      15 joint motions in each patient. Data analysis examined the change in total limb
      motion scores over time within patients undergoing neuroma-in-continuity
      resection and a comparison with those patients undergoing neurolysis. Compared
      with preoperative assessment, limb motion scores after neuroma resection were
      significantly decreased at 6 weeks, not significantly different by 3 months, and
      significantly improved at 12 months postoperatively. In comparison to patients
      undergoing neurolysis only, limb motion scores after neuroma resection were not
      significantly different at 3, 6, and 12 months postoperatively. These findings
      are unlikely to be accounted for by axonal regeneration across interpositional
      nerve grafts. Nerve regeneration or recovery in the nongrafted segment of the
      plexus must be sufficient to reproduce preoperative motion. Resection of the
      neuromas-in-continuity in obstetrical brachial plexus palsy does not
      significantly diminish motor activity.

PMID- 9774012
TI  - Leprosy affects facial nerves at the main trunk: neurolysis can possibly avoid
      transfer procedures.
AB  - The predilective sites of lesions in leprous peripheral nerves are well
      established, and their surgical decompression is common practice when
      sensorimotor disorders persist after medication. By contrast, the precise
      localization of leprous facial neuropathy still remains unclear, and
      musculofascial transfers have been the only type of surgical treatment. The goal
      of this study was to clarify where leprosy affects facial nerves and to determine
      whether neurolysis might suffice to restore facial function. In five Indian and
      two Egyptian patients suffering from leprous facial neuritis, the nerves were
      stimulated transcranially at the brainstem to evoke efferent motor nerve action
      potentials, which were recorded from the exposed nerves. Lesions were detected at
      the main trunk proximally from the first bifurcation in all cases. Epineuriotomy
      revealed fibrosis of the interfascicular epineurium in all instances, as an
      indication for interfascicular neurolysis. One patient was able to close his eye
      and showed a better smile soon after surgery. After 16 and 21 months,
      respectively, one patient had improved distinctly, two patients slightly, two
      patients showing no progress, and two patients were lost to follow-up. It is
      concluded that (1) leprous facial neuropathy is located at the main trunk close
      to the first bifurcation and not exclusively at the peripheral zygomatic
      branches, (2) microsurgical neurolysis can be considered in leprous facial
      neuropathy before transfer procedures as long as voluntary or spontaneous
      activity is present in the affected muscles, and (3) intraoperative transcranial
      electrical stimulation is an effective means of localizing the site and proximal
      extent of leprous facial neuropathy.

PMID- 9774014
TI  - Long-term results of surgical treatment for macrodactyly of the hand.
AB  - A retrospective review was performed for 23 patients who were surgically treated
      for macrodactyly of the hand between 1964 and 1995. Treatment regimens varied
      among the patients, and more than two operative procedures were performed in 65
      percent of the patients. At final follow-up, the average length of the affected
      digits was 102 percent of that of the normal contralateral side. The average
      circumference of the digits was 121 and 124 percent at the proximal
      interphalangeal and distal interphalangeal joints, respectively. The average
      range of motion was 65, 57, and 37 degrees at the metacarpophalangeal, proximal
      interphalangeal, and distal interphalangeal joints, respectively. Although it is
      difficult to compare treatment regimens, epiphysiodesis/epiphysectomy was quite
      effective in the prevention of longitudinal overgrowth of the digits, but
      resection of the hypertrophic nerves was unsuccessful in preventing finger
      overgrowth.

PMID- 9774013
TI  - Functional outcome after soft-tissue reconstruction for limb salvage after
      sarcoma surgery.
AB  - Limb salvage has been achieved for patients with sarcoma by means of
      compartmental resection, soft-tissue reconstruction, and adjuvant therapy without
      increased rates of local recurrence, metastasis, or mortality. Despite the
      prevalence of limb salvage procedures in the treatment of these tumors,
      relatively little information has been published regarding late functional
      results in these reconstructed extremities. This study reports on the functional
      outcome for soft-tissue reconstruction for limb salvage in patients with sarcoma.
      Over the past 6 years, 28 patients were treated for sarcomas of the extremity in
      which soft-tissue reconstruction was needed for complete limb salvage. The mean
      age of these patients was 48 years (range, 14 to 83 years); there were 14 male
      and 14 female patients. Of the 28 sarcomas, 23 cases involved the lower extremity
      and 5 cases were in the upper extremity. Reconstruction was performed primarily
      in 12 patients; 16 reconstructions were performed secondarily because of wound
      complications after initial extirpation. Adjuvant radiation therapy was
      administered either preoperatively or postoperatively in all cases. Of the 33
      reconstructive procedures performed in these 28 patients, 16 involved free flaps
      and 17 involved local flaps. All patients achieved initial limb salvage after the
      reconstructive procedure(s). Mean follow-up was 38 months. Twenty patients were
      available for the evaluation portion of the study. Two patients had delayed
      amputations: one for recurrent disease and another for osteoradionecrosis. Two
      patients died before beginning the examination process: one patient from the
      sarcoma and another patient from colon cancer. Twenty of the remaining 24
      patients agreed to participate and were examined using the Enneking outcome
      measurement scale. Patients were examined for range of motion, deformity,
      stability, pain level, strength, functional activity, and emotional acceptance
      and assigned a numerical score for each category. Based on this, an overall
      rating of excellent, good, fair, or poor was assigned. Nine patients (45 percent)
      achieved an overall rating of excellent, five patients (25 percent) achieved a
      rating of good, and six patients (30 percent) achieved a fair score. None had
      received a rating of poor. There were no differences in the results obtained
      comparing upper versus lower extremity, immediate versus delayed reconstruction,
      or reconstructions performed with a free flap versus a pedicled flap. This study
      supports the continued use of soft-tissue reconstruction for limb salvage in
      sarcoma surgery with good to excellent late functional results obtained in the
      majority of patients.

PMID- 9774015
TI  - Comparison of two different delay procedures in a rat skin flap model.
AB  - The overall objective of this study was to investigate how a strategic delay
      procedure could generate large flaps survival. On the basis of the vascular
      anatomy in 10 rats, a long three-territory skin flap spanning the length of the
      rat dorsum was designed. This flap was distally based on the deep circumflex
      iliac artery. The adjacent territories consisted of a large perforator of the
      posterior intercostal artery and the lateral thoracic artery in sequence. Two
      different vascular delay procedures were used and compared in nine animals. One
      dorsal midline incision was used to perform the two different delay procedures.
      The limited delay technique was performed by ligating a large cutaneous
      perforator of the posterior intercostal artery on one side of the rat. The
      extensive delay procedure was completed by ligating the cutaneous perforators of
      the posterior intercostal artery and the lateral thoracic artery on the other
      side of the rat. After a delay period of 10 days, the paired flaps were elevated,
      respectively, and sutured back in place. Seven days later, the area of viable
      skin flap was measured by the paper template technique. The animals were then
      killed, and the dorsal skin arteriograms were obtained by injecting a lead oxide
      mixture. Vascular changes of the paired flaps were assessed. In the extensive
      delay group, 100-percent survival was seen in four animals and distal partial
      necrosis was observed in five animals. The average survival area in the extensive
      delay group was 85.5 +/- 14.2 percent (mean +/- SD), whereas the flaps in limited
      delay group showed 100-percent survival in all animals (p < 0.05). In flaps that
      survived completely, the choke vessels among three vascular territories
      anastomosed throughout the flap. In the partially necrotic flaps, some choke and
      true anastomoses existed between the deep circumflex iliac and the posterior
      intercostal artery territories and the flap necrosis occurred in the third
      territory. This study suggests that the limited delay technique (ligation of one
      artery in the territory adjacent to the base of the flap) was the more effective
      delay procedure in the rat dorsal skin flap model.

PMID- 9774016
TI  - Reduction of skin flap necrosis by transdermal application of buflomedil bound to
      liposomes.
AB  - The influence of the vasoactive drug buflomedil hydrochloride bound to liposomes
      (2 mg/ml) was investigated in an arterial pattern skin flap model using the ear
      of hairless mice. For flap creation, the ear is cut at four-fifths of its base,
      which leaves the anterior artery as the only feeding vessel of the flap.
      Liposomes were locally applied daily for 30 minutes up to 5 days after flap
      creation. Microvascular perfusion in the proximal, central, and distal parts of
      the flap was measured by laser Doppler flowmetry. The border between perfused and
      nonperfused tissue was visualized by intravital fluorescence microscopy using
      fluorescein isothiocyanate (FITC)-labeled dextran (Mr 150,000) for contrast
      enhancement of microvessels. The area of nonperfused tissue was assessed by
      digital planimetry. Five days after flap creation the nonperfused area amounted
      to 23.8 +/- 3.1 percent of total flap surface in treated ears compared with 46.1
      +/- 5.6 percent in untreated ears (p < 0.05) of the contralateral side.
      Additional preoperative treatment for 5 days did not further reduce the area of
      nonperfused tissue (treated ears, 23.0 +/- 1.3 percent; control ears, 44.6 +/-
      5.1 percent). Microvascular perfusion was higher in the postoperatively treated
      ears in all parts of the flap from day 1 after flap creation until termination of
      the experiment. Five days after flap creation, perfusion as measured by laser
      Doppler flowmetry was reduced to 46.0 +/- 10.8 percent in the distal part in
      control ears compared with 91.9 +/- 8.3 percent (p < 0.05) in treated animals.
      Additional preoperative treatment for 5 days did not result in further
      improvement. It is concluded that local application of the vasoactive drug
      buflomedil docked to liposomes could be of therapeutic use in the treatment of
      ischemic tissue, including skin flaps.

PMID- 9774017
TI  - Increased proliferative activity of osteoblasts in congenital hemifacial
      hypertrophy.
AB  - Congenital hemifacial hypertrophy is expressed in facial asymmetry resulting from
      unilateral overgrowth. We examined proliferative activity of primary cultured
      osteoblasts taken from the hemifacial hypertrophic side of an 18-year-old woman
      compared with the normal side. Both fetal calf serum and basic fibroblast growth
      factor stimulated osteoblast DNA synthesis, and cultured osteoblast proliferation
      was markedly increased in the hypertrophic side. Neutralizing antibody against
      basic fibroblast growth factor was effective to partially block fetal calf serum
      induced DNA synthesis. These results suggest that fibroblast growth factor and
      its receptor signal transduction axis may be selectively involved in affected
      osteoblasts, leading to progression of congenital hemifacial hypertrophy.

PMID- 9774018
TI  - Leech therapy in the management of acute venous congestion of an infant's lower
      limb.
AB  - We report the successful use of leech therapy in the postsurgical management of
      an infant with acute venous congestion of an entire lower limb. Two days of
      constant leech therapy, followed by 5 days of intermittent application,
      decongested the affected tissues. There were no complications related to the
      leech therapy, and mild cutaneous hyperpigmentation was the only long-term
      complication of the acute venous congestion. The volume of the affected tissue
      may limit the success of leech therapy in cases of acute venous congestion in the
      limbs of adults. Nevertheless, the use of leeches to manage acute venous
      congestion of large portions of infants' bodies should be considered when
      surgical therapies are not feasible.

PMID- 9774019
TI  - Breast reconstruction in a male with a transverse rectus abdominis flap.
AB  - The TRAM flap may be the best choice in male breast reconstruction not just
      because it can replace the missing skin and fat but also because it may be a
      source of hair-bearing skin similar to the native breast skin.

PMID- 9774020
TI  - One-stage reconstruction of an infected skin and Achilles tendon defect with a
      composite distally planned lateral arm flap.
AB  - In this paper, the treatment of a complicated Achilles tendon defect with a
      composite lateral arm flap with distal design of the skin paddle has been
      presented. The extended portion of the flap was sufficient to restore adequate
      contour to the posterior aspect of the ankle, and reinervation showed good
      protective sensation at 1 year. In terms of resurfacing, the use of the
      reinervated lateral arm flap with a distal design of the skin paddle seems
      advantageous. The weakening of the reconstructed Achilles tendon, although
      without clinical incidence and impairment of elbow extensors at this stage, may
      indicate that a better substitute than the triceps tendon has to be found.
      Nevertheless, we would best reconstruct such an Achilles tendon defect by the
      same technique because of the well vascularized autologous tissue it provides,
      limiting the risk of infection.

PMID- 9774021
TI  - Laparoscopic incisional hernia repair after transverse rectus abdominis
      myocutaneous flap reconstruction.
AB  - Abdominal wall herniation is a relatively rare but well recognized complication
      that is known to occur following TRAM flap mobilization. Herein is presented a
      novel means to approach such a hernia, using the minimally invasive surgical
      approach to repair the defect with a piece of prosthetic material.

PMID- 9774022
TI  - Autologous fat injection for treatment of fecal incontinence: manometric and
      echographic assessment.

PMID- 9774023
TI  - Endoscopic transthoracic dorsal sympathectomy for the treatment of upper
      extremity hyperhidrosis: a new minimally invasive approach.
AB  - Palmar and axillary hyperhidrosis are best treated surgically by endoscopic
      transthoracic upper dorsal sympathectomy. At present, this methodology relies on
      (at least) double trocar insertion (per side), carbon dioxide insufflation, or
      both. We present a new minimally invasive endoscopic transthoracic technique,
      performed by a single-entry specifically modified thoracoscope and without the
      need for carbon dioxide insufflation, with the aim to reduce the drawbacks
      associated with the above-mentioned, currently adopted endoscopic technique. In
      our opinion, this "single-entry" technique, compared with the other reported
      approaches, should theoretically minimize any damage to the intercostal
      neurovascular bundle, while avoiding the complications related to carbon dioxide
      insufflation.

PMID- 9774024
TI  - Neo-flaps for facial reconstruction: can we create the desired thin-skin flaps?

PMID- 9774025
TI  - Muscle stapling technique for free muscle transfer to the face.
AB  - Free muscle transfer for facial reanimation can be facilitated by the use of a
      linear gastrointestinal stapler. This technique not only offers reliable muscle
      insertion at the recipient site but also helps to provide an adequate motor unit
      by facilitating safe muscle debulking, splitting, and tailoring.

PMID- 9774026
TI  - Treatment of an isolated outer table frontal sinus fracture using endoscopic
      reduction and fixation.
AB  - A case of an isolated frontal sinus fracture, reduced, fixed with miniplates and
      screws, and using the endoscopic technique, was presented. This case demonstrates
      the safety, efficacy, and economy of the endoscopic technique in properly
      selected cases that do not involve posterior table fractures or injury to the
      nasofrontal duct. The technique avoids the use of general anesthesia and the
      potential morbidities of coronal flaps.

PMID- 9774027
TI  - The zygorbicular dissection in composite rhytidectomy: an ideal midface plane.
AB  - Composite rhytidectomy added the repositioning of the orbicularis oculi muscle to
      the deep plane face lift to achieve a more harmonious appearance of the face by
      adding periorbital rejuvenation. By not separating the orbicularis oculi from the
      zygomaticus minor and by extending the dissection under medial portions of the
      zygomaticus major and minor muscles, a more significant improvement in composite
      rhytidectomy can now be achieved. A thin nonrestrictive mesentery between the
      deep plane face lift dissection and the zygorbicular dissection still allows
      vertical movement of the composite face lift flap without interrupting the
      intimate relationship between the platysma, cheek fat, and orbicularis oculi
      muscle. This modification eliminates the occasional prolonged edema and
      occasional temporary dystonia previously observed. It allows the continuation of
      the use of the arcus marginalis release, which has also been modified by
      resetting the septum orbitale over the orbital rim. These two modifications allow
      a more predictable and impressive result. They reinforce the concept of
      periorbital rejuvenation as an integral part of facial rejuvenation, which not
      only produces a more harmonious immediate result but prevents the possible
      unfavorable sequelae of conventional rhytidectomy and lower blepharoplasty.

PMID- 9774028
TI  - Frequent face lift sequelae: hollow eyes and the lateral sweep: cause and repair.
AB  - Traditional face lift and blepharoplasty techniques are based on two consistent
      principles. Conventional face lift techniques have always incorporated unopposed
      lateral vector tissue advancement, which is typical of subcutaneous lifts or
      rhytidectomies that include the platysma muscle (SMAS) or cheek fat (malar fat).
      When they are not adequately repositioned, the tissues of the lower eyelid and
      upper cheek continue to age, which may create a "lateral sweep" of the lower face
      as those malar soft tissues descend at a more rapid rate than the repositioned
      SMAS. Removal of the lower eyelid fat in conventional blepharoplasties may also
      lead to a more hollow-appearing lower eyelid. Hollow eyes and the lateral sweep
      could be prevented with a rhytidectomy technique that includes orbicularis
      repositioning and preservation of the lower eyelid fat with an arcus marginalis
      release. All patients who have been operated on who exhibit these unfavorable
      signs can have an impressive correction by utilizing the principles of
      superomedial vector orbicularis repositioning to counter the "lateral sweep" and
      arcus marginalis release to recreate a youthful shallow and narrow lower eyelid
      contour. This technique is invaluable to patients seeking secondary surgery to
      regain harmony of the rejuvenated face.

PMID- 9774029
TI  - Treatment of photodamaged skin with topical tretinoin: an update.
AB  - The utility of topical tretinoin in combination with sun protection has now been
      formally established as a useful approach to the treatment of sun-damaged skin.
      The early observations of our group have been confirmed in numerous well
      controlled clinical trials. Moreover, a great deal is known about structural and
      even molecular changes induced by topical tretinoin, which account for the
      clinical benefits achieved by this agent. A great deal has been learned in a very
      short period of time, and these findings represent another major use of retinoid
      therapy in dermatologic disease.

PMID- 9774030
TI  - Paranasal implants for correction of midface concavity.
AB  - Central midface concavity was corrected with the placement of porous polyethylene
      implants in the paranasal area. This simulated the effect of skeletal osteotomies
      and advancement without altering dental occlusion. Implants were placed to
      correct congenital, posttraumatic, and cleft-related skeletal midface retrusion
      in nine patients. In seven of the patients, paranasal augmentation was performed
      in conjunction with rhinoplasty. There have been no implant-related complications
      during a mean 33-month follow-up (range 5 to 83 months). Screw fixation of these
      implants ensures stable positioning and allows precise final contouring during
      surgery.

PMID- 9774031
TI  - The impact of liposuction on body fat.
AB  - Routine liposuction has very low perioperative complication rates and is thus
      considered to be innocuous. Some authors have even proposed that large-volume
      liposuction could be therapeutic. However, because subcutaneous adipose tissue
      has nutritional and thermodynamic metabolic functions proportional to the
      absolute amount and the distribution of fat, it is possible that removal of
      subcutaneous adipose tissue might be detrimental. We measured the amount of fat
      removed by large-volume (>1000 cc) liposuction and expressed the results in terms
      of absolute and relative changes in total body fat and in visceral adipose tissue
      (nonsubcutaneous adipose tissue) in 63 normal weight to mildly obese women (n =
      51) and men (n = 12). Aspiration of 1.5 +/- 0.7 kg (mean +/- SD) of lipid in
      women removed 9.2 +/- 3.2 percent of body fat or 10.5 percent of subcutaneous
      adipose tissue corresponding to a 12-percent increase in the ratio of visceral to
      subcutaneous adipose tissue. One third of the women (n = 17) had a mean increase
      of 16 percent (range 13 to 21 percent) in the proportion of visceral fat. In the
      12 men, aspiration of 1.7 +/- 0.6 kg of lipid removed 9.8 +/- 2.9 percent of body
      fat or 12.7 +/- 3.6 percent of subcutaneous adipose tissue, resulting in a 14
      percent increase in the ratio of visceral to subcutaneous fat. The correlation
      between aspirate and body mass index was 0.57 (p < 0.001). Although large-volume
      subcutaneous liposuction removed relatively little body fat, it led to
      significant increases in the proportion of visceral adipose tissue. Because the
      proportion of visceral adipose tissue is a risk factor for metabolic
      complications of obesity, the metabolic effects of large-volume liposuction need
      to be evaluated.

PMID- 9774032
TI  - Minimizing complications of ultrasound-assisted lipoplasty: an initial experience
      with no related complications.
AB  - Numerous complications and increased operating times were reported with
      ultrasonically assisted lipoplasty in the first several months after introduction
      of the technology in the United States. The purpose of this study was to review
      early reported complications and management regimens, evaluate possible causes of
      problems, and apply indications and techniques to attempt to minimize
      complications during an initial experience with this technique beginning in
      January of 1997. Seven specific indications and modifications of existing
      techniques were developed and applied to an initial clinical series of 70
      consecutive patients who underwent ultrasound-assisted suction lipoplasty between
      January 10, 1997, and August 1, 1997. Follow-up ranged from 1 to 7 months. No
      perioperative or postoperative complication occurred in any patient in this
      series. In this series of ultrasound-assisted lipoplasty cases, application of
      the following criteria resulted in a series of 70 patients with 1 to 7-month
      follow-up without complications: (1) selecting patients with well localized fat
      deposits who were no more than 20 percent above their ideal body weight; (2)
      infusing a solution of Ringer's Lactate containing 1 cc of 1:1000 epinephrine per
      1000 cc into the area of fat removal, stopping infusion when the tissues first
      become firm, not infusing to marked tissue turgor or skin induration; (3)
      restricting the level of energy application to a minimum of 1 cm from the
      undersurface of the dermis; (4) limiting ultrasonic energy application in each
      area to approximately 1 minute per estimated 100 cc of total aspirate in a wet to
      superwet environment; (5) not performing ultrasound-assisted lipoplasty in the
      same area as another procedure that could potentially compromise tissue
      vascularity; (6) using a Lysonix 2000 generator and 5-mm golf tee tip probe at a
      power setting of 8 to apply ultrasonic energy to the area of fat removal, ceasing
      energy application when tissue resistance to the passage of the probe decreases
      and moving the cannula as rapidly as tissue resistance allows; and (7) using a
      standard elastic garment without adherent foam or other materials for 2 weeks
      postoperatively, encouraging all normal activity immediately, and restricting
      aerobic activities for 2 weeks.

PMID- 9774033
TI  - Large-volume liposuction and extensive abdominoplasty: a feasible alternative for
      improving body shape.
AB  - Forty-two female patients underwent liposuction of large volumes and extensive
      abdominoplasty during an 18-month period, with an average follow-up period of 9
      months. Fifty-two percent of the patients underwent a third surgical procedure,
      which was basically aesthetic. The average age was 40 years; weight varied
      between 51 kg and 113 kg, with only 11 percent of the patients at their ideal
      weight. The tumescent technique was used for performing liposuction, which was
      done on the loins, trochanters, lumbar, upper scapular, and upper lateral
      abdominal regions, avoiding liposuction of the abdominal flap in all cases except
      for one. The abdominoplasty was extensive with detachment to the xiphoid process
      without detaching liposuctioned areas. Volumes of 1600 ml to 11,200 ml were
      obtained through liposuction, with an average of 4230 cc, and minimal blood loss.
      Fatty dermal tissue was removed through abdominoplasty and it varied between 400
      g and 5000 g with an average of 1300 g. Only the two heaviest patients required
      an autologous blood unit, because they underwent breast reduction at the same
      time. All the other patients were managed exclusively with intravenous
      crystalloids solutions. No major complications arose, and only five patients had
      minor complications. Based on these results, we consider it to be feasible to
      combine the liposuctioning of large volumes with abdominoplasty to improve body
      shape, even with the addition of a third surgical procedure. Nevertheless, it is
      essential to use the tumescent technique for liposuction to reduce bleeding to a
      minimum and to allow us to perform other procedures.

PMID- 9774034
TI  - Cyst formation after fat injection.
AB  - Autologous fat injection has been widely used during the past 20 years to correct
      contour anomalies. We have been using suction-assisted lipectomy for the past 13
      years, and we have used the aspirated fat to correct contour irregularities on
      several occasions. We present the case of a 44-year-old woman who, after
      autologous fat transplantation to correct a contour anomaly (depression secondary
      to a previous operation) at her left groin, developed a large cyst containing
      pearl-like fat lobules. The cyst was first noticed 3 months postoperatively and
      was removed under local anesthesia 5 months postoperatively. Histology confirmed
      that the lobules were mature fat cells.

PMID- 9774035
TI  - Midline platysma muscular overlap for neck restoration.
AB  - A variation of platysmaplasty, consisting in the overlapping (double-breasted
      fashion) of the platysma muscles in the midline, solely through submental
      approach, is described. It allows excellent platysmal suspension and neck
      recontouring, eliminating the need of posterior traction of the platysma muscle
      and avoiding in many cases the cervical incisions.

PMID- 9774036
TI  - Lower eyelid volume augmentation with fat pearl grafting.

PMID- 9774037
TI  - New technique for scarless umbilical reinsertion in abdominoplasty procedures.
AB  - The most visible scar in the conventional abdominoplasty procedure or TRAM flap
      donor site closure is the scar around the reinserted umbilicus. In an attempt to
      increase the aesthetic outcome, the authors have introduced a new technique of
      umbilical reconstruction and reinsertion during abdominoplasty avoiding any
      paraumbilical scar, which results in a more natural appearance in that area. This
      new technique, potential pitfalls, and long-term results are reported.

PMID- 9774039
TI  - Four patients you love to hate.

PMID- 9774038
TI  - Prerandomization of clinical trials: a more ethical way for performing cleft
      palate research.

PMID- 9774040
TI  - Oncologic and plastic surgeons: colleagues, collaborators, teammates.

PMID- 9774041
TI  - Daniel Drake's account of his own hand burns (1830).

PMID- 9774042
TI  - Undermining of the scalp.

PMID- 9774043
TI  - Use of the step-advancement V-Y flap in the temporal region.

PMID- 9774044
TI  - Basal cell carcinoma presenting as a cleft earlobe.

PMID- 9774045
TI  - Repair of cleft earlobe using double opposing Z-plasty.

PMID- 9774046
TI  - Bilateral congenital circular defects of the alar cartilages of the nose.

PMID- 9774047
TI  - Columellar elongation in bilateral cleft lip.

PMID- 9774048
TI  - A plastic plug embedded in the hard palate of an infant.

PMID- 9774049
TI  - Osteoradionecrosis of the mandible.

PMID- 9774050
TI  - Bone face reconstruction with polymethylmethacrylate.

PMID- 9774052
TI  - CO2 laser resurfacing over facial flaps.

PMID- 9774051
TI  - Complications and toxicities of implantable biomaterials for facial aesthetic and
      reconstructive surgery.

PMID- 9774053
TI  - The use of bovie pad for feathering the edges with laser resurfacing.

PMID- 9774054
TI  - A case of free flap failure and internal jugular vein occlusion.

PMID- 9774055
TI  - Cost of immediate versus delayed breast reconstruction.

PMID- 9774056
TI  - Chest wall reconstruction for sternal wound infection after internal mammary and
      gastroepiploic coronary artery bypass.

PMID- 9774057
TI  - Brown pigmentation in painful double lumen breast implants.

PMID- 9774058
TI  - Infiltrating duct carcinoma encountered in paraffin-injected breast.

PMID- 9774059
TI  - Incidence of breast carcinoma in patients having reduction mammaplasty.

PMID- 9774060
TI  - Late postoperative infection in a breast reduction case.

PMID- 9774061
TI  - The pectoralis major pedicle trap.

PMID- 9774062
TI  - Glans penis in hypospadias.

PMID- 9774063
TI  - Anal spinchter reconstruction with bilateral gracilis muscle flap.

PMID- 9774064
TI  - A method for facilitating splint placement in tenorrhaphy.

PMID- 9774065
TI  - Posterior interosseous syndrome resulting from deep tissue massage.

PMID- 9774066
TI  - Recurrent digital ischemia caused by thrombosis of the persistent median artery.

PMID- 9774067
TI  - Combined median and ulnar entrapment neuropathies.

PMID- 9774068
TI  - Flap vascularity after free musculocutaneous tissue transfer.

PMID- 9774069
TI  - Dead man walking?

PMID- 9774070
TI  - Miracles of plastic surgery.

PMID- 9774071
TI  - The split medial gastrocnemius muscle flap.

PMID- 9774072
TI  - The calcaneal subtendinous space for passage of the pedicle in free-flap
      reconstruction of lateral ankle defects.

PMID- 9774073
TI  - An unusual indication for replantation.

PMID- 9774074
TI  - Exposure to atomic radiation and the subsequent development of cutaneous
      malignancy.

PMID- 9774075
TI  - Modulation of ultraviolet light-induced epidermal damage: beneficial effects of
      tocopherol.

PMID- 9774076
TI  - Evaluation of Artecoll versus Zyplast.

PMID- 9774077
TI  - The First Asia-Pacific Conference on Cutaneous Surgery and Laser Therapy.

PMID- 9774079
TI  - Artificial leech technique.

PMID- 9774078
TI  - A new protocol for prolonged general anesthesia in rabbits.

PMID- 9774080
TI  - Operating room glasses.

PMID- 9774081
TI  - "Who are we?".

PMID- 9774082
TI  - "Will the real plastic surgeon please stand up?".

PMID- 9774083
TI  - Sudden infant death syndrome in an identical twin with complete unilateral cleft
      lip and palate.

PMID- 9774084
TI  - Malaria research deal seeks to make up for industry's retreat.

PMID- 9774085
TI  - Agencies to mitigate space station delays.

PMID- 9774086
TI  - NIH launches discussion of in utero gene therapy...and seeks to repair 'flaw' in
      review process.

PMID- 9774087
TI  - Canadian research councils publish joint code on ethics.

PMID- 9774088
TI  - NIH ponders role of 'public' advisers.

PMID- 9774089
TI  - Plight of US postdocs...in the US.

PMID- 9774090
TI  - Hope or hype for lexipafant?

PMID- 9774091
TI  - Animals at the Salk.

PMID- 9774092
TI  - Evolutionary biology. Origin of the spider's head.

PMID- 9774093
TI  - Protein transport. The doors to organelles.

PMID- 9774094
TI  - Immunology. Sinking surveillance's flagship.

PMID- 9774095
TI  - Sighting of the swinging lever arm of muscle.

PMID- 9774096
TI  - Neurobiology. See and grasp.

PMID- 9774097
TI  - Thomas Kreis (1952-98)

PMID- 9774098
TI  - Haeckel's hierarchies.

PMID- 9774099
TI  - Pollen analysis reveals murder season.

PMID- 9774100
TI  - The ubiquitin pathway in Parkinson's disease.

PMID- 9774101
TI  - Whale ankles and evolutionary relationships.

PMID- 9774103
TI  - The atomic structure of the bluetongue virus core.
AB  - The structure of the core particle of bluetongue virus has been determined by X
      ray crystallography at a resolution approaching 3.5 A. This transcriptionally
      active compartment, 700 A in diameter, represents the largest molecular structure
      determined in such detail. The atomic structure indicates how approximately 1,000
      protein components self-assemble, using both the classical mechanism of quasi
      equivalent contacts, which are achieved through triangulation, and a different
      method, which we term geometrical quasi-equivalence.

PMID- 9774102
TI  - The X-linked lymphoproliferative-disease gene product SAP regulates signals
      induced through the co-receptor SLAM.
AB  - In addition to triggering the activation of B- or T-cell antigen receptors, the
      binding of a ligand to its receptor at the cell surface can sometimes determine
      the physiological outcome of interactions between antigen-presenting cells, T and
      B lymphocytes. The protein SLAM (also known as CDw150), which is present on the
      surface of B and T cells, forms such a receptor-ligand pair as it is a self
      ligand. We now show that a T-cell-specific, SLAM-associated protein (SAP), which
      contains an SH2 domain and a short tall, acts as an inhibitor by blocking
      recruitment of the SH2-domain-containing signal-transduction molecule SHP-2 to a
      docking site in the SLAM cytoplasmic region. The gene encoding SAP maps to the
      same area of the X chromosome as the locus for X-linked lymphoproliferative
      disease (XLP) and we found mutations in the SAP gene in three XLP patients.
      Absence of the inhibitor SAP in XLP patients affects T/B-cell interactions
      induced by SLAM, leading to an inability to control B-cell proliferation caused
      by Epstein-Barr virus infections.

PMID- 9774104
TI  - Terrain influences the accurate judgement of distance.
AB  - Mathematically, three-dimensional space can be represented differently by the
      cartesian, polar, and other coordinate systems. However, in physical sciences,
      the choice of representation system is restricted by the need to simplify a
      machine's computation while enhancing its efficiency. Does the brain, for the
      same reasons, 'select' the most cost-efficient way to represent the three
      dimensional location of objects? As we frequently interact with objects on the
      common ground surface, it might be beneficial for the visual system to code an
      object's location using a ground-surface-based reference frame. More precisely,
      the brain could use a quasi-two-dimensional coordinate system (x(s), y(s)) with
      respect to the ground surface (s), rather than a strictly three-dimensional
      coordinate system (x, y, z), thus reducing coding redundancy and simplifying
      computations. Here we provide support for this view by studying human
      psychophysical performance in perceiving absolute distance and in visually
      directed action tasks. For example, when an object was seen on a continuous,
      homogeneous texture ground surface, the observer judged the distance to the
      object accurately. However, when similar surface information was unavailable, for
      example, when the object was seen across a gap in the ground, or across distinct
      texture regions, distance judgement was impaired.

PMID- 9774105
TI  - Shape selectivity in primate lateral intraparietal cortex.
AB  - The extrastriate visual cortex can be divided into functionally distinct temporal
      and parietal regions, which have been implicated in feature-related ('what') and
      spatial ('where') vision, respectively. Neuropsychological studies of patients
      with damage to either the temporal or the parietal regions provide support for
      this functional distinction. Given the prevailing modular theoretical framework
      and the fact that prefrontal cortex receives inputs from both temporal and
      parietal streams, recent studies have focused on the role of prefrontal cortex in
      understanding where and how information about object identity is integrated with
      (or remains segregated from) information about object location. Here we show that
      many neurons in primate posterior parietal cortex (the 'where' pathway) show
      sensory shape selectivities to simple, two-dimensional geometric shapes while the
      animal performs a simple fixation task. In a delayed match-to-sample paradigm,
      many neuronal units also show significant differences in delay-period activity,
      and these differences depend on the shape of the sample. These results indicate
      that units in posterior parietal cortex contribute to attending to and
      remembering shape features in a way that is independent of eye movements,
      reaching, or object manipulation. These units show shape selectivity equivalent
      to any shown in the ventral pathway.

PMID- 9774106
TI  - Mechanism of calcium gating in small-conductance calcium-activated potassium
      channels.
AB  - The slow afterhyperpolarization that follows an action potential is generated by
      the activation of small-conductance calcium-activated potassium channels (SK
      channels). The slow afterhyperpolarization limits the firing frequency of
      repetitive action potentials (spike-frequency adaptation) and is essential for
      normal neurotransmission. SK channels are voltage-independent and activated by
      submicromolar concentrations of intracellular calcium. They are high-affinity
      calcium sensors that transduce fluctuations in intracellular calcium
      concentrations into changes in membrane potential. Here we study the mechanism of
      calcium gating and find that SK channels are not gated by calcium binding
      directly to the channel alpha-subunits. Instead, the functional SK channels are
      heteromeric complexes with calmodulin, which is constitutively associated with
      the alpha-subunits in a calcium-independent manner. Our data support a model in
      which calcium gating of SK channels is mediated by binding of calcium to
      calmodulin and subsequent conformational alterations in the channel protein.

PMID- 9774107
TI  - Replication checkpoint requires phosphorylation of the phosphatase Cdc25 by Cds1
      or Chk1.
AB  - Checkpoints maintain the order and fidelity of events of the cell cycle by
      blocking mitosis in response to unreplicated or damaged DNA. In most species this
      is accomplished by preventing activation of the cell-division kinase Cdc2, which
      regulates entry into mitosis. The Chk1 kinase, an effector of the DNA-damage
      checkpoint, phosphorylates Cdc25, an activator of Cdc2. Phosphorylation of Cdc25
      promotes its binding to 14-3-3 proteins, preventing it from activating Cdc2. Here
      we propose that a similar pathway is required for mitotic arrest in the presence
      of unreplicated DNA (that is, in the replication checkpoint) in fission yeast. We
      show by mutagenesis that Chk1 functions redundantly with the kinase Cds1 at the
      replication checkpoint and that both kinases phosphorylate Cdc25 on the same
      sites, which include serine residues at positions 99, 192 and 359. Mutation of
      these residues reduces binding of 14-3-3 proteins to Cdc25 in vitro and disrupts
      the replication checkpoint in vivo. We conclude that both Cds1 and Chk1 regulate
      the binding of Cdc25 to 14-3-3 proteins as part of the checkpoint response to
      unreplicated DNA.

PMID- 9774108
TI  - Efficiency of signalling through cytokine receptors depends critically on
      receptor orientation.
AB  - Human erythropoietin is a haematopoietic cytokine required for the
      differentiation and proliferation of precursor cells into red blood cells. It
      activates cells by binding and orientating two cell-surface erythropoietin
      receptors (EPORs) which trigger an intracellular phosphorylation cascade. The
      half-maximal response in a cellular proliferation assay is evoked at an
      erythropoietin concentration of 10 pM, 10(-2) of its Kd value for erythropoietin
      EPOR binding site 1 (Kd approximately equal to nM), and 10(-5) of the Kd for
      erythropoietin-EPOR binding site 2 (Kd approximately equal to 1 microM). Overall
      half-maximal binding (IC50) of cell-surface receptors is produced with
      approximately 0.18 nM erythropoietin, indicating that only approximately 6% of
      the receptors would be bound in the presence of 10 pM erythropoietin. Other
      effective erythropoietin-mimetic ligands that dimerize receptors can evoke the
      same cellular responses but much less efficiently, requiring concentrations close
      to their Kd values (approximately 0.1 microM). The crystal structure of
      erythropoietin complexed to the extracellular ligand-binding domains of the
      erythropoietin receptor, determined at 1.9 A from two crystal forms, shows that
      erythropoietin imposes a unique 120 degrees angular relationship and orientation
      that is responsible for optimal signalling through intracellular kinase pathways.

PMID- 9774109
TI  - Tom40 forms the hydrophilic channel of the mitochondrial import pore for
      preproteins [see comment].
AB  - The mitochondrial outer membrane contains machinery for the import of preproteins
      encoded by nuclear genes. Eight different Tom (translocase of outer membrane)
      proteins have been identified that function as receptors and/or are related to a
      hypothetical general import pore. Many mitochondrial membrane channel activities
      have been described, including one related to Tim23 of the inner-membrane protein
      import system; however, the pore-forming subunit(s) of the Tom machinery have not
      been identified until now. Here we describe the expression and functional
      reconstitution of Tom40, an integral membrane protein with mainly beta-sheet
      structure. Tom40 forms a cation-selective high-conductance channel that
      specifically binds to and transports mitochondrial-targeting sequences added to
      the cis side of the membrane. We conclude that Tom40 is the pore-forming subunit
      of the mitochondrial general import pore and that it constitutes a hydrophilic,
      approximately 22 A wide channel for the import of preproteins.

PMID- 9774110
TI  - Drosophila CBP represses the transcription factor TCF to antagonize Wingless
      signalling.
AB  - T-cell factor (TCF), a high-mobility-group domain protein, is the transcription
      factor activated by Wnt/Wingless signalling. When signalling occurs, TCF binds to
      its coactivator, beta-catenin/Armadillo, and stimulates the transcription of the
      target genes of Wnt/Wingless by binding to TCF-responsive enhancers.
      Inappropriate activation of TCF in the colon epithelium and other cells leads to
      cancer. It is therefore desirable for unstimulated cells to have a negative
      control mechanism to keep TCF inactive. Here we report that Drosophila CREB
      binding protein (dCBP) binds to dTCF. dCBP mutants show mild Wingless
      overactivation phenotypes in various tissues. Consistent with this, dCBP loss-of
      function suppresses the effects of armadillo mutation. Moreover, our data show
      that dCBP acetylates a conserved lysine in the Armadillo-binding domain of dTCF,
      and that this acetylation lowers the affinity of Armadillo binding to dTCF.
      Although CBP is a coactivator of other transcription factors, our data show that
      CBP represses TCF.

PMID- 9774111
TI  - Urinary schistosomiasis.

PMID- 9774112
TI  - Renal dysplasia: new approaches to an old problem.
AB  - Renal dysplasia is a clinically important consequence of abnormal nephrogenesis.
      Various forms are encountered in clinical practice; however, renal dysplasia may
      represent the final common end point of defects in the normal cascade of fetal
      kidney development. Typical histopathologic changes characterize renal dysplasia,
      including architectural distortion, metaplasia, and primitive glomeruli and
      tubules. Cystic changes are not universal but can be found in most situations.
      The advent of recent molecular techniques, including gene targeting and
      positional cloning, has expanded our knowledge of the molecular control of normal
      mammalian nephrogenesis and with it our understanding of the pathogenesis of
      renal dysplasia. A defect in the ability of the branching ureteric duct and the
      undifferentiated metanephric blastema to communicate appears to be the basic
      underlying principle for the formation of dysplasia. Mutation, defective
      regulation of transcription, and alteration in spatial or temporal expression of
      a number of classes of genes, including growth factors, have been implicated in
      the development of renal dysplasia. Numerous examples, both experimental and in
      nature, highlight this point.

PMID- 9774113
TI  - Increased plasma metalloproteinase-9 concentrations precede development of
      microalbuminuria in non-insulin-dependent diabetes mellitus.
AB  - We determined plasma metalloproteinase-9 (MMP-9) concentrations in 30 patients
      with non-insulin-dependent diabetes mellitus (NIDDM) at an initial examination
      (baseline) and on three separate occasions during a 48-month follow-up period.
      All patients had normal urinary albumin excretion (<20 microg/min) at the first
      three examinations. At the fourth examination (48 months after the first
      examination), 22 patients had normal urinary albumin excretion and eight had
      microalbuminuria (median, 36.4 microg/min; range, 20.2 to 46.6 microg/min).
      Compared with patients with normal urinary albumin excretion, patients with
      microalbuminuria had significantly higher plasma levels of MMP-9 at the second
      (56+/-14 microg/L v36+/-12 microg/L; P < 0.05), third (88+/-23 microg/L v 39+/-14
      microg/L; P < 0.01), and fourth (117+/-30 microg/L v 44+/-16 microg/L; P < 0.01)
      examinations, but not at the first examination (34+/-12 microg/L v 33+/-14
      microg/L; P=NS). An increase in plasma MMP-9 concentrations preceded the
      occurrence of microalbuminuria within 4 years. The groups did not differ with
      regard to age, sex, duration of NIDDM, blood pressure, or mean glycated
      hemoglobin. In addition, the eight patients with microalbuminuria were treated
      with an angiotensin-converting enzyme inhibitor (cilazapril; 0.5 mg once daily)
      for 6 months. Microalbuminuria was reduced to within the normal range, and plasma
      MMP-9 concentrations were significantly decreased with the cilazapril treatment
      (52+/-18 microg/L; P < 0.01). However, serum MMP-1 and tissue inhibitor of MMP-1
      showed no change during the study period. These data suggest that plasma MMP-9
      concentrations preceded and may predict the development of microalbuminuria in
      NIDDM.

PMID- 9774114
TI  - Patterns of patient care reported by nephrologists: implications for nephrology
      training.
AB  - The recent estimate of the nephrology workforce indicates that more nephrologists
      must be trained to care for the increasing number of patients with end-stage
      renal disease (ESRD). This conclusion was based on a 1996 survey indicating that
      nephrologists devote an average of 35% of their activities caring for ESRD
      patients. We compared data in that survey with those from a 1991 survey of
      members of the American Society of Nephrology to determine similarities between
      the different periods. The 1,590 responders in the 1991 survey (35% of the
      American Society of Nephrology membership) indicated that 50% devoted more than
      75% of their effort to patient care, predominately for patients with general
      nephrology and hypertension problems. Approximately 69% of respondents cared for
      fewer than 50 hemodialysis patients, and the majority of respondents felt the
      maximum number of dialysis patients for whom they could provide adequate medical
      care would be 50. Most respondents felt that there would be a deficiency of
      nephrologists in their community within 5 years. Results from both the 1991 and
      1996 surveys indicate that practice patterns have not changed markedly; combining
      results from the two surveys makes it clear that more nephrologists are needed to
      care for the projected increase in dialysis patients. Because nephrologists
      should be involved in the management of the pre-ESRD patient, training programs
      will have to broaden the preparation of future nephrologists.

PMID- 9774115
TI  - Quality of life and psychosocial relationships in patients with chronic renal
      insufficiency.
AB  - The goal of the present study was to assess the psychological functioning level
      and the relationship between psychosocial variables and psychological functioning
      and social support buffering effects among a population of outpatients with
      chronic renal insufficiency (CRI). The Beck Depression Inventory, Illness Effects
      Questionnaire, Multidimensional Scale of Social Support, and Satisfaction With
      Life Scale were administered to 50 patients with CRI. The patients' nephrologist
      provided a Karnofsky scale rating to assess physical functioning. Sample scores
      were also compared for descriptive purposes to a previously reported sample of
      patients with more advanced disease and chronic renal failure (CRF), and a
      population of patients who had just started hemodialysis therapy for end-stage
      renal disease (ESRD). Patients with CRI are minimally depressed and perceive few
      negative illness effects. Satisfaction with life and cognitive depression scores
      were similar among the patients with CRI, CRF, and ESRD. Within the CRI sample,
      perception of illness, depression, and quality of life were significantly
      intercorrelated, indicating an emerging pattern of negative psychological
      reactions among some patients. Level of perceived social support was not
      correlated with other study variables. The mean level of perceived social support
      was lower among patients with CRI than in patients with ESRD. We conclude that
      even though most adjustment variables are in normal ranges, higher negative
      perception of illness is associated with higher depression scores and lower
      quality of life, even at this early stage of CRI. Additionally, social support
      may play an important role for those individuals beginning to experience a
      decline in renal functioning.

PMID- 9774116
TI  - An examination of the renal transplant evaluation process focusing on cost and
      the reasons for patient exclusion.
AB  - A medical evaluation of prospective renal transplant recipients is performed to
      identify conditions that may exclude patients from transplantation because of
      unacceptable risks. Protocols for evaluating potential transplant candidates are
      available, but there is little information about reasons for excluding patients
      from transplantation. To assess the effectiveness and cost of our renal
      transplant-recipient evaluation process, we retrospectively reviewed patients
      excluded from renal transplantation between January 1993 and December 1995 to
      categorize the reasons for exclusion. We also examined the costs of the
      evaluation. The study group included all adults referred for kidney-only
      transplantation during the study period who were excluded from transplantation
      (n=125). Demographics of the 160 patients with end-stage renal disease (ESRD) who
      underwent renal transplantation during the study period were also examined.
      Compared with the patients who underwent transplantation, the excluded patients
      were older (48+/-14 v 43+/-12 years; P=0.006) and more likely to be women (66 of
      125 patients; 53% v 57 of 160 patients; 36%; P=0.005) and diabetic (59 of 125
      patients; 47% v 30 of 160 patients; 19%; P=0.005). The most common reason for
      excluding patients was medical contraindication (46%), followed by patient
      declined (25%), obesity (10%, defined as a body mass index [BMI] > or = 35),
      patient death (6%), and insurance/financial (5%). The medical reasons for
      exclusion were heart disease (38%), noncompliance (28%), miscellaneous (22%), and
      cancer (12%). Tests performed after the initial evaluation included cardiac
      testing (stress thallium or echocardiography and coronary angiography) in 50
      patients, Doppler studies of the lower extremities in 28 patients, and hepatitis
      C polymerase chain reaction (PCR) or recombinant immunoblot assay (RIBA) assays
      in 8 patients. The cost of standard pretransplantation blood work for selected
      tests (ABO blood group typing, HLA, hepatitis B and C, and cytomegalovirus) was
      $709. Deferring such routine pretransplantation blood work until after the
      patient education session and history and physical examinations by nephrology and
      surgery in the 31 patients (25%) who declined transplantation at the initial
      visit would have resulted in considerable savings. Our evaluation process now
      includes prereferral information on a prospective recipient's medical problems,
      height and weight, and basic screening laboratory tests. This protocol has
      resulted in a more efficient and cost-effective evaluation process. Further
      examination of the cost-effectiveness of the transplant evaluation process is
      warranted.

PMID- 9774117
TI  - Changes in coagulation and fibrinolysis in the postoperative period immediately
      after kidney transplantation in patients receiving OKT3 or cyclosporine A as
      induction therapy.
AB  - Different immunosuppressive agents, in particular OKT3, have been implicated as
      causative factors in the risk for renal thrombosis in the period immediately
      after kidney transplantation. Also, in different types of vascular surgery, a
      state similar to hypercoagulation has been reported. To assess the extent to
      which OKT3, cyclosporine A (CsA), and surgery itself affect coagulation and
      fibrinolysis, a study was conducted of 20 patients divided into two groups: group
      A, 10 patients received OKT3 (first dose during the induction of anesthesia); and
      group B, 10 patients received CsA (first dose at least 2 hours before
      transplantation). Basal determinations and determinations at 2, 4, and 24 hours
      after the induction of anesthesia were made. No differences were found between
      the groups with respect to the clinical and usual coagulation parameters. The
      following were studied in both groups: (1) markers of coagulation activity
      (prekallikrein [PKK] levels and formation of thrombin-antithrombin complexes
      [TATc]), (2) inhibitors and suppressors of hemostasis (antithrombin III [AT-III]
      and protein C [PC] activity), (3) markers of fibrinolysis activation (levels of
      plasminogen [PLG] and of alpha2-antiplasmin [alpha2-APL]), and (4) markers of
      endothelial damage (tissue plasminogen activator [TPA] and thrombomodulin [TMD]).
      In both groups, an important formation of TATc was observed early, together with
      a decrease in PKK levels and consumption of both AT-III and PC, which reached
      their lowest levels at 24 hours. This points to an activation of coagulation
      through the intrinsic route and a secondary consumption of hemostasis inhibitors,
      both possibly caused by surgery. A consumption of PLG and alpha2-APL was also
      observed, reflecting stimulation of the fibrinolytic system and a physiological
      response to the activation of coagulation. A greater release of endothelial TPA
      was only observed in the patients receiving OKT3 (P < 0.0001), possibly signaling
      endothelial activation. It is concluded that surgical stress could be the major
      factor triggering the alterations seen in hemostasis and their possible
      consequences.

PMID- 9774118
TI  - Immunohistological and ultrastructural differences between recurrent type I
      membranoproliferative glomerulonephritis and chronic transplant glomerulopathy.
AB  - In renal transplant recipients with type I membranoproliferative
      glomerulonephritis (MPGN), the posttransplantation course can be complicated by a
      recurrence of the original disease. However, it is well known that a recurrence
      of type I MPGN and chronic transplant glomerulopathy (CTG) cannot easily be
      distinguished. It has been suggested that the two entities can be differentiated
      by using electron microscopy (EM) and immunofluorescence (IF) techniques.
      However, studies are lacking that compare biopsy specimens from patients with
      either a recurrence of type I MPGN or CTG. We have studied renal biopsy specimens
      from 10 patients with CTG and compared the ultrastructural and IF findings with
      biopsy specimens from 12 patients with a possible recurrence of type I MPGN. All
      the patients with CTG showed an electron-lucent zone of finely flocculent
      material in the subendothelial space, whereas all patients with a recurrence of
      type I MPGN showed subendothelial electron-dense deposits on EM. On IF, all
      patients with CTG showed Immunoglobulin M (IgM) with greater intensity than C3.
      For the patients with recurrent type I MPGN, the opposite was true. Eleven
      specimens showed C3 deposits with greater intensity than IgM, and in one patient,
      C3 and IgM were found in equal intensity. In conclusion, when IF and EM studies
      are available, CTG and recurrence of type I MPGN can reliably be distinguished.

PMID- 9774119
TI  - Immunoglobulin M and C1q mesangial labeling in IgA nephropathy.
AB  - Colabeling with complement compont C1q or immunoglobulin M (IgM) is occasionally
      reported in biopsy specimens from patients with IgA nephropathy. The significance
      of this finding has been questioned. In 83 children and young adults with
      otherwise typical IgA nephropathy, 15 patients had more than trace mesangial
      labeling for IgM or C1q. Of these, 14 patients (93%) had greater than 1 +
      proteinuria at the time of biopsy. This was in marked distinction to the patients
      with no mesangial labeling for these reactants, only 15% of whom had greater than
      1 + proteinuria. The children with IgM or C1q colabel did not differ from those
      lacking this finding in age at presentation, length of follow-up, or current
      renal function. In childhood IgA nephropathy, colabeling with IgM or C1q is seen
      frequently, probably is a function of heavy proteinuria at the time of biopsy,
      and does not contribute adversely to outcome.

PMID- 9774120
TI  - Tubulointerstitial mast cell infiltration in glomerulonephritis.
AB  - Mast cells are involved in chronic inflammation and tissue fibrosis. To determine
      whether these cells are also involved in tubulointerstitial injury in
      glomerulonephritis, we assayed mast cell infiltration in the kidneys of 107
      patients with primary or secondary glomerulonephritis. Using a monoclonal
      antihuman tryptase antibody, we detected mast cells in the renal cortical
      tubulointerstitium, the periglomerular areas, and the medullary interstitium, but
      not in glomeruli. Renal cortical tubulointerstitial mast cells, including
      periglomerular area, were estimated as 0.8+/-1.6 cells/mm2 in minimal change
      nephrotic syndrome (n=7), 1.5+/-0.7 cells/mm2 in minor glomerular abnormalities
      without nephrotic syndrome (n=7), 6.5+/-7.7 cells/mm2 in membranous
      nephropathy(n=10), 12.9+/-15.5 cells/mm2 in lupus nephritis (n=15), 13.4+/-8.3
      cells/mm2 in focal segmental glomerular sclerosis (n=6), 18.5+/-21.1 cells/mm2 in
      ANCA-related nephropathy (n=5), 19.8+/-14.2 cells/mm2 in membranoproliferative
      glomerulonephritis (n=5), 21.3+/-17.7 cells/mm2 in immunoglobulin A (IgA)
      nephropathy (n=42), and 33.0+/-33.8 cells/mm2 in diabetic nephropathy (n=10).
      Except for patients with the rapidly progressive glomerulonephritic syndrome
      (RPGN), the number of infiltrating mast cells significantly correlated with the
      serum concentration of creatinine at the time of renal biopsy (r=0.59; P <
      0.0001) and with the intensity of tubulointerstitial injury as measured by
      leukocyte infiltration (r=0.72; P < 0.0001) and fibrosis (r=0.75; P < 0.0001). In
      contrast, mast cell infiltration did not correlate with urinary protein
      excretion. In relation to serum creatinine concentration, the number of mast
      cells was fewer in patients with RPGN than in those with chronic
      glomerulonephritis. These data suggest that mast cells may contribute to the
      renal deterioration in glomerulonephritis by inducing chronic tubulointerstitial
      injury.

PMID- 9774121
TI  - Role of down-regulated CHIF mRNA in the pathophysiology of hyperkalemia of acute
      tubular necrosis.
AB  - Acute tubular necrosis (ATN) is associated with hyperkalemia. We have shown that
      the medulla is the main site of impaired sodium (Na+)/potassium (K+) pump
      activity in ATN. CHIF, a gene that evokes K+ conductance in oocytes, is regulated
      in the colon by aldosterone and in the kidney by K+ intake. It is assumed that
      CHIF has a role in K+ homeostasis. To characterize the impaired K+ handling in
      ATN, the effect of impaired renal function on CHIF mRNA expression in the kidney
      and colon was studied. Three groups of rats with glycerol-induced ATN were
      studied: (1) control group, (2) moderate-ATN group, and (3) severe-ATN group.
      Serum creatinine levels in the control group were 45+/-2.1 micromol/L; in the
      moderate-ATN group, 224.8+/-16.9 micromol/L; and in the severe-ATN group, 376.5+/
      15.9 micromol/L. In the group with severe ATN, significant hyperkalemia (P <
      0.001 v control group) was noted. The expression of CHIF mRNA in relative units
      (percentage of control) in the moderate-ATN group, in the medulla, papilla, and
      colon, was 16.3%+/-5.6% (P < 0.001), 94.2%+/-9.3% (P=not significant ), and
      165.9%+/-11.1% (P < 0.001); and in the severe-ATN group was 11.1%+/-6.4% (P <
      0.001), 73.7%+/-4% (P < 0.001), and 310.8%+/-27.3% (P < 0.001), respectively.
      These results show that (1) in both moderate and severe ATN, CHIF mRNA is
      dramatically reduced in the medulla, (2) in severe ATN, CHIF mRNA expression
      decreases in the papilla, and (3) CHIF mRNA is upregulated in direct relationship
      to the severity of ATN and to the levels of aldosterone in the colon. These
      results suggest that the hyperkalemia that occurs in severe ATN stems at least in
      part from the downregulation of CHIF mRNA in the kidney medulla and papilla. The
      compensatory increase in colonic CHIF mRNA is not sufficient to maintain normal
      serum K+ levels.

PMID- 9774122
TI  - Blunted pressure natriuretic response in the old rat: participation of the renal
      nerves.
AB  - With advancing age, there is a generalized reduction in the ability of the kidney
      to generate a natriuretic response and, in addition, the incidence of salt
      sensitive hypertension increases. One event that could link these changes is a
      defect that develops in the pressure natriuresis response of the old kidney. To
      test this possibility, we conducted studies on the anesthetized, male Sprague
      Dawley rat to determine the effect of abrupt alterations of renal perfusion
      pressure (RPP) on urinary sodium excretion (U(Na)V). Young (3- to 5-month-old),
      middle-aged (11- to 13-month-old), and old (18 to 20-month-old) rats were
      studied, and RPP was varied by clamping the aorta during the infusion of a
      cocktail of vasoactive hormones that suppressed the activity of endogenous
      factors. The gain of the pressure natriuresis relationship was severely
      attenuated in the old rat compared with the young and middle-aged rats. This
      blunting of the pressure natriuresis relationship in the old rat was partially
      attenuated by acute renal denervation. This effect was not associated with marked
      alterations in the filtered load of sodium, implying that aging is associated
      with a loss of the tubular epithelial response to an acute change in RPP. These
      observations suggest that the blunted pressure natriuresis may have a role in the
      increased incidence of salt-sensitive hypertension and that increased renal nerve
      activity may have a contributory role.

PMID- 9774123
TI  - Treatment of atherosclerotic ostial renal artery stenosis with the intravascular
      stent.
AB  - Traditional approaches to revascularization for atherosclerotic ostial renal
      artery stenosis (RAS) have been suboptimal because of the invasiveness and
      relatively high perioperative morbidity and mortality of surgery and the low
      rates of success and long-term patency with percutaneous renal angioplasty
      (PTRA). We report our 5-year (1991 to 1996) experience with the intravascular
      stent (Palmaz stent; Johnson & Johnson, Miami Lakes, FL) for the treatment of
      ostial RAS in 129 patients (63 men, 66 women) and 148 arteries. The mean age of
      the patients was 71+/-10 years; 98% were hypertensive and 57% had renal
      dysfunction. Angiographic characteristics of RAS were unilateral in 78%,
      bilateral in 15%, and single kidney in 7%. The technical success rates were 98%
      for stent versus 11% for PTRA in the ostial location. The stent restenosis rate
      (angiographic) was 14% at 8+/-5 months. Systolic and diastolic blood pressures
      were as follows: baseline, 158+/-3 and 84+/-2 mm Hg; 6 months, 149+/-3 and 81+/-2
      mm Hg; 12 months, 149+/-3 and 79+/-2 mm Hg; and 24 months, 135+/-3 and 79+/-2 mm
      Hg. Follow-up values were significantly lower than baseline (P < 0.05). The
      number of medications for hypertension initially decreased from 2.2+/-0.1 at
      baseline to 1.6+/-0.1 and 1.8+/-0.1 at 1 and 3 months, respectively (P < 0.05).
      By 6 months, however, the number of medications had increased and was not
      significantly different from before stent placement. Renal function was stable in
      the group as a whole: Cockroft-Gault creatinine clearance (C-G CrCl) at baseline
      was 40+/-2 mL/min; at 6 months, 36+/-3 mL/min; at 12 months, 39+/-3 mL/min; and
      at 24 months, 39+/-4 mL/min. When stratified by degree of renal function, values
      were similarly stable. Patients with a baseline serum creatinine level of 2 mg/dL
      or less had C-G CrCl values as follows: baseline, 53+/-3 mg/dL; 6 months, 43+/-4
      mg/dL; 12 months, 46+/-4 mg/dL; and 24 months, 52+/-5 mg/dL. Those with a
      baseline serum creatinine level greater than 2 mg/dL had C-G CrCl values as
      follows: baseline, 26+/-2 mg/dL; 6 months, 31+/-4 mg/dL; 12 months, 32+/-6 mg/dL;
      and 24 months, 23+/-3 mg/dL. Of eight patients who were dialysis dependent, four
      (50%) recovered renal function with a mean serum creatinine level of 2.3+/-0.5
      mg/dL at 15+/-6 months (range, 9 to 24 months). Stent placement for the treatment
      of atherosclerotic ostial RAS has a high success rate and a low rate of
      restenosis. Control of hypertension improves in most patients. Renal function
      stabilizes or improves in the majority of patients, even those with severe renal
      failure. These favorable outcomes are maintained long term.

PMID- 9774124
TI  - Differing outcomes of gram-positive and gram-negative peritonitis.
AB  - Peritonitis remains the leading cause of patient dropout from continuous
      peritoneal dialysis (CPD) therapy. Few studies have compared patient morbidity,
      mortality, and outcome for patients undergoing CPD who develop gram-positive and
      gram-negative peritonitis. We retrospectively reviewed the charts of patients who
      developed either gram-positive or gram-negative peritonitis between January 1,
      1993, and December 31, 1995. Three hundred seventy-five patients who developed
      415 episodes of gram-positive and gram-negative peritonitis were maintained on
      CPD therapy during this time period. There was no difference in age, race, and
      sex between patients who developed gram-positive or gram-negative peritonitis.
      More patients with diabetes developed gram-negative peritonitis than gram
      positive peritonitis (53% v 40%, respectively; P < 0.05). Coagulase-negative
      staphylococcal species accounted for 47% of all gram-positive episodes, whereas
      Klebsiella organisms, Escherichia coli, and Enterobacter organisms accounted for
      63% of all gram-negative episodes. Significantly more patients who developed gram
      positive peritonitis continued CPD therapy 2 weeks and 6 months after the onset
      of peritonitis than patients who developed gram-negative peritonitis (97% v 73%;
      P < 0.05 at 2 weeks and 81% v 58% at 6 months; P < 0.05, respectively). Nine
      percent of the patients who developed gram-positive peritonitis died within 6
      months after the onset of peritonitis, whereas 21% of the patients who developed
      gram-negative peritonitis died (P < 0.05). Patients who developed gram-negative
      peritonitis were significantly more likely to require hospitalization than
      patients who developed gram-positive peritonitis (74% v 24%; P < 0.001). More
      patients with gram-negative peritonitis required peritoneal catheter removal than
      patients with gram-positive peritonitis (18% v 4%; P < 0.001). Thirty-two percent
      of the patients who developed gram-positive peritonitis re-developed an episode
      of peritonitis with the same organism compared with only 9% of the patients who
      developed gram-negative peritonitis. Furthermore, peritonitis recurrence with the
      same organism within 6 months after the initial episode was noted in 60% of the
      patients with peritonitis caused by Staphylococcus aureus compared with 24% of
      patients with peritonitis caused by other gram-positive organisms (P < 0.05). We
      conclude that the outcomes of gram-positive and gram-negative peritonitis are
      different. When rates of peritonitis are used to predict outcome, it appears that
      gram-positive and gram-negative peritonitis rates need to be examined separately.

PMID- 9774125
TI  - Risk of death among chronic dialysis patients infected with hepatitis C virus.
AB  - Hepatitis C virus (HCV) infection is highly prevalent among chronic dialysis
      patients (10% to 40%) and is the most common cause of chronic liver disease.
      However, there are no studies estimating the risk for death among dialysis
      patients infected with HCV compared with those not infected. We conducted a
      prospective cohort study to estimate the risk for death among chronic dialysis
      patients infected with HCV compared with those not infected. In 1992, 200
      patients (91%) who had been undergoing dialysis therapy for at least 6 months
      consented to be screened for HCV infection by enzyme immunoblot assay and
      polymerase chain reaction (PCR). Information about potential confounders and
      potential risk factors for death and HCV infection was obtained from the dialysis
      center database. Patient outcomes collected included death, transplantation, and
      loss to follow-up. The Cox proportional hazards model was used to estimate the
      odds of death among dialysis patients who were positive for the HCV antibody and
      HCV RNA compared with negative patients. Forty-four patients (22%) were HCV
      antibody positive. Thirty-four patients (17%) were HCV RNA positive. Patients in
      the HCV RNA-positive group were more likely to be younger (51.8+/-12.6 v 57.2+/
      17.3 years of age), men (77% v 54%), and black (65% v 37%). None of the home
      hemodialysis or peritoneal dialysis patients were HCV RNA positive, whereas one
      of the home hemodialysis and one of the peritoneal dialysis patients were HCV
      antibody positive. Two patients became infected with HCV during the follow-up
      period. Patients who were HCV RNA positive and those who were HCV antibody
      positive were at increased risk for death compared with patients who were
      negative (adjusted relative risk [aRR]=1.78; 95% confidence interval [CI], 1.01
      to 3.14; P=0.045; and aRR=1.97; 95% CI, 1.16 to 3.33; P=0.012, respectively),
      after adjusting for time on dialysis, race, transplantation, and age. We conclude
      that HCV infection increased the risk for death during the study period compared
      with those not infected. Further studies should assess the measures used to
      prevent and treat HCV infection.

PMID- 9774126
TI  - Prospective evaluation of an anemia treatment algorithm in hemodialysis patients.
AB  - Current guidelines recommend maintaining the hematocrits of chronic hemodialysis
      patients in the low to mid-30s. Maintaining patients' hematocrits within a narrow
      range requires frequent monitoring of their hematocrits and iron studies and
      periodic adjustment of erythropoietin doses and administration of intravenous
      iron. We designed a simple anemia treatment algorithm to streamline the
      management of anemia in hemodialysis patients. The protocol required formal
      monthly decisions about the administration of intravenous iron or changes in
      erythropoietin dose. This algorithm was implemented by dialysis nurses and
      evaluated prospectively for 6 months in a single dialysis unit (30 patients). The
      proportion of patients whose hematocrits were within the desired target (31% to
      35%) increased from 27% at baseline to 61% during months 4 through 6 of the
      algorithm. Conversely, the proportion of patients whose hematocrit values were
      below the target decreased from 46% at baseline to 18% during months 4 through 6
      of the algorithm (P=0.004). The percentage of patients whose hematocrit values
      were above the target did not increase. The proportion of patients whose
      transferrin saturation was less than 18% decreased from 47% at baseline to 20%
      during months 4 through 6 of the algorithm (P=0.04). The weekly erythropoietin
      dose administered decreased from 11,200+/-1,400 units at baseline to 9,400+/
      1,200 units in month 6 of the algorithm (P=0.06). We conclude that a simple
      anemia treatment algorithm implemented by dialysis nurses is feasible and
      efficacious and may increase the proportion of hemodialysis patients whose
      hematocrit values are within the target range, without increasing erythropoietin
      requirements.

PMID- 9774127
TI  - Ofloxacin clearance during hemodialysis: a comparison of polysulfone and
      cellulose acetate hemodialyzers.
AB  - The pharmacokinetics of ofloxacin were studied in 13 patients with end-stage
      renal disease during hemodialysis using two different dialyzers: a polysulfone
      membrane (Fresenius F6) and a cellulose acetate dialyzer (Nissho Nipro FB-150T).
      All patients received 100 mg ofloxacin orally per day before dialysis. The
      hemodialysis clearance per square meter surface area was significantly different,
      with 5.0+/-0.7 L/h and 3.7+/-1.6 L/h, respectively. The serum concentration was
      reduced by a 3-hour hemodialysis by 49.6%+/-5.8% per square meter surface area
      and 45.5%+/-4.8% per square meter surface area. The half-life was 4.2+/-1.8 hours
      and 4.8+/-1.6 hours during the hemodialysis period and 22.8+/-2.2 hours and
      23.3+/-1.7 hours between the dialysis sessions, respectively. Comparing
      polysulfone and cellulose acetate dialyzers, the material of the membrane
      influences the half-life, the dialysis clearance, and the percentage of drug
      extracted during hemodialysis. We conclude that the type of dialyzer used has to
      be taken into account in dosage recommendations for antimicrobial therapy in
      hemodialysis patients.

PMID- 9774128
TI  - Anti-glomerular basement membrane disease and dual positivity for antineutrophil
      cytoplasmic antibody in a patient with membranous nephropathy.
AB  - We present the case of a 50-year-old man who underwent kidney biopsy for
      nephrotic syndrome. In addition to a membranous pattern, anti-glomerular basement
      membrane (anti-GBM) staining was noted before manifestations of anti-GBM disease.
      Hematuria and renal failure ensued 2 weeks later. In addition, he had
      simultaneous circulating levels of anti-GBM antibody and both perinuclear (P-)
      and cytoplasmic (C-) antineutrophil cytoplasmic antibody (ANCA).

PMID- 9774129
TI  - Combined membranous nephropathy and IgA nephropathy.
AB  - IgA nephropathy (IgAN) and membranous nephropathy (MN) are both common renal
      biopsy findings that rarely have been described together in the same patient. The
      significance of this finding is not clear. We present the clinical and
      pathological data of four patients with combined MN-IgAN and discuss possible
      pathogenetic mechanisms. By definition, all cases showed immunodominant mesangial
      deposits of IgA (+/-C3) and subepithelial capillary wall deposits of IgG (+/-C3)
      by immunofluorescence microscopy, confirmed by electron microscopy. There were
      three men and one woman, whose ages ranged from 41 to 67 years (average, 51.7
      years). All four presented with microscopic hematuria and proteinuria, three in
      the nephrotic range. Renal function was normal in three individuals, and one
      subject had mild renal insufficiency accompanied by long-standing hypertension.
      Two other patients had newly uncovered hypertension. Complement levels were
      normal in all subjects. One patient had a positive antinuclear antibody (ANA)
      test, but none had other serologic or clinical features diagnostic of lupus. None
      of the four individuals had any other predisposing factors for either MN or IgAN,
      including hepatitis B infection. All four patients had stable renal function at
      last determination (average follow-up, 24 months; range, 4 to 34 months), with
      markedly reduced proteinuria in three individuals and persistent heavy
      proteinuria in one. A review of the literature indicates that combined MN-IgAN is
      most often characterized by heavy proteinuria and stable renal function. Some
      cases may be related to hepatitis B infection, but in most instances the cause is
      unknown. The combination of these two pathological processes does not result in a
      particularly deleterious clinical outcome for patients.

PMID- 9774130
TI  - Budd-Chiari syndrome during nephrotic relapse in a patient with resistance to
      activated protein C clotting inhibitor.
AB  - It has long been known that patients with nephrotic syndrome have a
      hypercoagulable state, which explains the association between nephrotic syndrome,
      renal vein thrombosis, and thromboembolism. However, the Budd-Chiari syndrome has
      never been reported in nephrotic patients. This is the first report of such an
      association that, most likely, depended on a primary resistance to activated
      protein C.

PMID- 9774131
TI  - Pregnancy in a nonimmunosuppressed transplant recipient.
AB  - A 30-year-old woman with a living related six-antigen-matched kidney allograft
      conceived 10 years posttransplantation. She had discontinued her
      immunosuppression medications 3 years previously. The allograft functioned well
      throughout gestation, which was complicated by preeclampsia, leading to induction
      at 35 weeks and delivery of a 2,175-g male.

PMID- 9774132
TI  - Dilated uremic cardiomyopathy in a dialysis patient cured by persistent
      ultrafiltration.
AB  - A patient is presented who after 2 years of hemodialysis showed all of the
      features of congestive cardiomyopathy to a very severe degree: dilation of all
      cardiac compartments, increased left ventricular mass, low ejection fraction,
      diastolic disturbances, third- to fourth-degree mitral and tricuspid
      regurgitation, ascites, and low blood pressure. All of these abnormalities
      gradually but completely disappeared during 5 months of persistent
      ultrafiltration during or between dialysis sessions. It was concluded that
      chronic fluid overload was a major factor in the cardiac disease of this patient.
      Unrecognized hidden fluid overload has long been known (but also neglected), and
      its prevention deserves top priority in chronic dialysis patients.

PMID- 9774134
TI  - Nephrology workforce and time allocation: important issues for the future.

PMID- 9774133
TI  - Plasma matrix metalloproteinase-9 and diabetic microalbuminuria: tip of the
      iceberg?

PMID- 9774135
TI  - When a stranger offers a kidney: ethical issues in living organ donation.

PMID- 9774136
TI  - Antidiuretic hormone and renal clearance of uric acid.

PMID- 9774137
TI  - Rapid development of drug-induced lupus nephritis in the absence of extrarenal
      disease in a patient receiving procainamide.

PMID- 9774138
TI  - Ultrasonography in nephrology.

PMID- 9774140
TI  - Src, N-methyl-D-aspartate (NMDA) receptors, and synaptic plasticity.
AB  - The protein tyrosine kinase Src is expressed widely in the central nervous system
      and is abundant in neurons. Over the past several years, evidence has accumulated
      showing that one function of Src is to regulate the activity of N-methyl-D
      aspartate (NMDA) receptors and other ion channels. NMDA receptors are a principal
      subtype of glutamate receptor that mediates fast excitatory transmission at most
      central synapses. Recently it has been discovered that, by means of up-regulating
      the function of NMDA receptors, Src mediates the induction of long-term
      potentiation (LTP) in the CA1 region of the hippocampus. This finding led to a
      new model for induction of LTP whereby tetanic stimulation produces a rapid
      activation of Src, causing enhanced NMDA receptor function. This enhanced NMDA
      receptor function boosts the entry of Ca2+, which may thereby trigger the
      downstream signalling cascade, ending in potentiation of non-NMDA receptors. This
      functional role for Src may be important in physiological and pathophysiological
      processes in the central nervous system.

PMID- 9774141
TI  - Phospholipase D in rat myocardium: formation of lipid messengers and synergistic
      activation by G-protein and protein kinase C.
AB  - Activation of phospholipase D (PLD) and phosphoinositide-specific phospholipase C
      (PI-PLC) by fluoride, to stimulate heterotrimeric G-proteins, and by phorbol
      esters, to stimulate protein kinase C (PKC), was studied in rat atria. Fluoride
      and 4beta-phorbol-12beta,13alpha-dibutyrate (PDB), in contrast to 4beta-phorbol
      13alpha-acetate (PAc), activated PLD, catalyzing the formation of [3H]
      phosphatidylethanol ([3H]-PETH), [3H]-phosphatidic acid ([3H]-PA), choline and sn
      1,2-diacylglycerol (DAG). Basal PLD activity was resistant to drastic changes in
      Ca2+ and to Ro 31-8220, a PKC inhibitor, but was decreased by genistein, an
      inhibitor of tyrosine kinase, and increased by vanadate, a tyrosine phosphatase
      inhibitor; both effects were, however, very small. Fluoride-evoked PLD activity
      was resistant to Ro 31-8220 and to genistein, but was Ca2+-dependent. The rate of
      fluoride-induced PLD activation was maintained for at least 60 min. In contrast,
      PDB-mediated PLD activity was blocked by Ro 31-8220 and was resistant to
      extracellular Ca2+-depletion and desensitized within ca. 15 min. PDB markedly
      potentiated the fluoride-evoked generation of [3H]-phosphatidylethanol and of
      choline, but inhibited the formation of [3H]-inositol phosphates ([3H]-IP(1-3)).
      Ethanol (2%) blocked the PDB-evoked generation of both [3H]-phosphatidic acid and
      of sn-1,2-diacylglycerol, whereas fluoride-evoked responses were reduced only to
      approximately 50%. In conclusion, the trimeric G-protein-PLD pathway in heart
      tissue did not enclose PKC activation and was long-lasting and Ca2+-dependent;
      there was no evidence for an involvement of tyrosine phosphorylation. However,
      PKC activation modulated G-protein-coupled PLD and PI-PLC activities in opposite
      directions. PLD activity significantly contributed to the mass production of sn
      1,2-diacylglycerol in the heart. The evidence for a pathophysiological role of
      PLD activation in cardiac hypertrophy and in ischemic preconditioning is
      discussed.

PMID- 9774139
TI  - Ahr null alleles: distinctive or different?
AB  - Two independent laboratories have generated Ahr "null" or "knockout" mice that
      share some common characteristics but also have distinct phenotypes. In this
      Commentary, we will discuss our view of the candidate variables that might
      account for these differences. More importantly, we hope that this discussion can
      identify important parameters to be assessed by investigators in the process of
      characterizing their own modified loci. The variables that we have considered
      include the possibility that different targeting strategies can result in altered
      products with unsuspected function or that the targeting event itself can alter
      the function of neighboring genes. Further, genetic background can have an
      important influence on phenotype, and differences in genome can be introduced
      during derivation by the type of embryonic stem cells used and by the random
      segregation of parental genes in the F2 generation of line propagation. In
      addition, phenotype may be acutely sensitive to environmental variables, such as
      pathogen and chemical exposure and stress introduced by crowding and disease.
      Finally, we discuss approaches to resolving differences between null mice and
      propose a partial solution, the institution of a repository for detailed
      information on targeted alleles that may not typically be allowed in today's
      "fast paced" scientific publications.

PMID- 9774142
TI  - Chemical synthesis and biological properties of novel fluorescent antifolates in
      Pgp- and MRP-overexpressing tumour cell lines.
AB  - We have synthesised a series of fluorescent analogues of methylbenzoprim, a
      diaminopyrimidine antifolate which we have previously shown to exhibit in vivo
      antitumour activity in a methotrexate (MTX) "transport-resistant" tumour cell
      line. The analogues bear the dansyl, nitrobenzoxodiazole or methoxycoumarin
      fluorophores. The cytotoxicity of the compounds was evaluated using the 3-[4,5
      dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay
      against two human lung cancer cell lines, together with their multidrug resistant
      (MDR) sublines. H69/P is a small cell line and its multidrug resistant subline
      H69/LX4 overexpresses P-glycoprotein (Pgp). COR-L23/P is a large cell line and
      its multidrug resistant subline COR-L23/R overexpresses the multidrug resistance
      associated protein (MRP). IC50 values for the compounds (i.e. concentration to
      reduce cell growth by 50%) in the 3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide assay ranged from 0.20 to 0.81 microM in the H69
      parental line and from 0.83 to 5.10 microM in the COR-L23 parent line. The MDR
      sublines both showed clear cross-resistance to each of the compounds, with
      resistance factors (ratio of IC50 value in resistant vs parental cell line)
      ranging from 16 to 137 in H69/LX4 and from 5 to 16 in COR-L23/R. For compounds
      (10) and (11) where drug accumulation was studied using flow cytometry,
      resistance was associated with an approximately 10-fold reduction in cellular
      drug accumulation over a period of 30 min. The drug resistance modifiers
      verapamil (used at 6.6 microM) and cyclosporin A (used at 4.2 microM) were tested
      for their ability to sensitise the resistant lines. Whereas verapamil showed
      little activity, cyclosporin A partially restored the activity of compound (10),
      and fully restored the activity of compound (11) in H69/LX4 cells. This
      sensitisation of H69/LX4 by cyclosporin A was associated with a partial
      restoration of the drug accumulation deficit in this line. Hence, these novel
      lipophilic antifolates appear to be substrates for both the P-glycoprotein and
      MRP resistance mechanisms. Therefore, although they have been designed to
      overcome one mechanism of methotrexate resistance, namely impaired drug
      transport, this has been achieved only at the cost of rendering them susceptible
      to alternative mechanisms.

PMID- 9774143
TI  - Decreased expression of gamma-glutamyltranspeptidase in the intestinal cell line
      Caco-2 by inducers of cytochrome P450 1A1.
AB  - Our purpose was to investigate whether inducers of cytochrome P450 1A1 (CYP1A1),
      which cause a decreased expression in Caco-2 cells, at both the mRNA and protein
      levels, of membrane proteins associated with the uptake and transport of hexoses,
      would also affect the expression of gamma-glutamyltranspeptidase (gammaGT) (EC
      2.3.2.2). In Caco-2 clonal TC7 cells grown under standard conditions (25 mM
      glucose), exposure to beta-naphthoflavone (beta-NF), 2,3,7,8-tetrachlorodibenzo-p
      dioxin, and 3-methylcholanthrene resulted in increased glucose consumption and
      decreased gammaGT activity in cells grown to confluence, i.e. when the
      differentiation is optimum. GammaGT activity was further analyzed during the time
      course of differentiation of TC7 cells treated or not with beta-naphthoflavone:
      while gammaGT activity in untreated cells showed a 10-fold increase from the
      exponential phase of growth until late postconfluence, gammaGT activity in beta
      NF-treated cells, although increasing by 4-fold, remained at a much lower level
      (<25%). This decreased activity of gammaGT was associated with a decreased level
      of gammaGT mRNA. This inhibiting effect was not dependent on the CYP1A1 activity,
      as it also occurred in the presence of CYP1A1 inhibitors such as alpha
      naphthoflavone, 8-methoxypsoralen or ellipticin. It was however dependent on
      glucose supply as it was not observed when the cells were cultured in low glucose
      (1 mM). These results raise the question of whether, in Caco-2 cells, CYP1A1
      inducers or the signal transduction system which controls CYP1A1 are involved in
      the regulation of the expression of gammaGT through a mechanism involving glucose
      metabolism.

PMID- 9774144
TI  - Catecholic iron complexes as cytoprotective superoxide scavengers against
      hypoxia:reoxygenation injury in isolated hepatocytes.
AB  - Reactive oxygen species including superoxide radicals (O2-.) have been implicated
      in the pathogenesis of radiotherapy, ischemia-reperfusion injury, aging, and
      inflammatory diseases. In the present work, 2:1 catecholic iron complexes were
      found to be more effective than uncomplexed catechols at protecting hepatocytes
      against hypoxia:reoxygenation cell injury. They also decreased markedly the level
      of reactive oxygen species formed before cytotoxicity ensued. Furthermore, these
      catecholic iron complexes were also more effective than uncomplexed catechols at
      scavenging superoxide radicals generated both enzymatically and nonenzymatically.
      The superoxide radical scavenging activity of catecholic iron complexes seemed to
      correlate with the redox potential of catechols. These results suggest that
      cytoprotection by catechols may involve an initial chelation with iron to form a
      complex that is a much more effective superoxide radical scavenger than the
      catechol itself.

PMID- 9774145
TI  - Preferential effects of nicotine and 4-(N-methyl-N-nitrosamine)-1-(3-pyridyl)-1
      butanone on mitochondrial glutathione S-transferase A4-4 induction and increased
      oxidative stress in the rat brain.
AB  - We have investigated the in vivo effects of the tobacco-specific toxins nicotine
      and 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on antioxidant
      defense systems in the mitochondrial, microsomal, and cytosolic compartments of
      rat brain, lung, and liver. Nicotine induced maximum oxidative stress in brain
      mitochondria, as seen from a 1.9-fold (P < 0.001) increase in thiobarbituric acid
      reactive substance (TBARS) and a 2-fold (P < 0.001) increase in glutathione S
      transferase (GST) A4-4 (also referred to as rGST 8-8) activities. These changes
      were accompanied by a 25-40% increase in reactive oxygen species and a 20-30%
      decrease in alcohol dehydrogenase activities. The 4-(N-methyl-N-nitrosamino)-1-(3
      pyridyl)-1-butanone-induced oxidative damage was apparent in the microsomal
      fraction of brain, lung, and liver, and it also increased 4-hydroxynonenal
      specific GST A4-4 activity in the brain and lung mitochondrial matrix fraction.
      The levels of microsomal thiobarbituric acid reactive substance, cytochrome
      P4502E1 activity, and reactive oxygen species were also increased significantly
      (P < 0.001) in all tissues. Both of these toxins induced the level of GST A4-4
      mRNA in the brain, while they caused a marked reduction in the liver GST A4-4
      mRNA pool. Additionally, the brain mitochondrial matrix showed a markedly higher
      level of 4-hydroxynonenal specific GST activity and mGST A4-4 antibody-reactive
      protein than did the cytosolic fraction. In conclusion, the present study
      provides evidence for the occurrence of GST A4-4 enzyme activity in mammalian
      mitochondria, in addition to demonstrating that both mitochondria and microsomes
      are intracellular targets for nicotine- and NNK-induced organ toxicity.

PMID- 9774146
TI  - Enhancement of doxorubicin content by the antitumor drug lonidamine in resistant
      Ehrlich ascites tumor cells through modulation of energy metabolism.
AB  - The effect of the antitumor drug lonidamine (LND) on respiration, aerobic
      glycolysis, adenylate pool, doxorubicin (DOX) uptake, and efflux in DOX-resistant
      and DOX-sensitive Ehrlich tumor cells was investigated. The results may be
      summarized as follows: 1) In both types of cells, LND inhibited both respiration
      and glycolysis in a dose-dependent manner and lowered the ATP concentration. The
      effect was more marked in cells incubated in glucose-free medium; 2) LND raised,
      to a remarkable extent, the intracellular content of DOX in resistant and
      sensitive cells respiring on endogenous substrates because of reduced ATP
      availability, whereas in glucose-supplemented medium, where both respiration and
      glycolysis contributed to ATP synthesis, the increase was lower; and 3) when LND
      was added to DOX-loaded cells, it failed to significantly inhibit DOX efflux
      because of time-dependent phenomena. These findings indicated that LND, a drug
      currently employed in tumor therapy, might also be useful in reducing or
      overcoming multidrug resistance (MDR) of those cells with a reduced ability to
      accumulate and retain antitumor drugs.

PMID- 9774147
TI  - Potent differentiation-inducing properties of the antiretroviral agent 9-(2
      phosphonylmethoxyethyl) adenine (PMEA) in the rat choriocarcinoma (RCHO) tumor
      cell model.
AB  - 9-(2-phosphonylmethoxyethyl)adenine (PMEA) and its closely related structural
      analogue (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) are potent inhibitors of
      retroviruses and hepatitis B virus. In its oral prodrug form (adefovir
      dipivoxil), PMEA is currently the subject of advanced phase II/III clinical
      trials for the treatment of HIV infections. PMEA has also been shown to be a
      potent differentiation-inducing agent. In the present study, PMEA was found to
      have a strong differentiation-inducing effect on rat choriocarcinoma (RCHO)
      cells, comparable to that of methotrexate, which is the drug of choice for the
      chemotherapy of choriocarcinoma in humans. PMEA induced differentiation of
      choriocarcinoma trophoblast cells in a concentration-dependent manner within the
      2- to 50-microM concentration range, as ascertained by giant cell formation,
      alkaline phosphatase induction, progesterone secretion, and the disappearance of
      a cytotrophoblast-specific surface antigen. PMEA had to be exposed to the rat
      choriocarcinoma cell cultures for at least 2-3 days to achieve optimal growth
      inhibition and differentiation of the tumor cells. Unlike PMEA, (R)-9-(2
      phosphonylmethoxypropyl)adenine failed to induce differentiation of proliferating
      cytotrophoblasts into nonproliferating, hormonally active giant cells. This
      points to the specificity of PMEA as an inducer of choriocarcinoma cell
      differentiation.

PMID- 9774148
TI  - PKC-independent modulation of multidrug resistance in cells with mutant (V185)
      but not wild-type (G185) P-glycoprotein by bryostatin 1.
AB  - Bryostatin 1 is a new antitumor agent which modulates the enzyme activity of
      protein kinase C (PKC, phospholipid-Ca2+-dependent ATP:protein transferase, EC
      2.7.1.37). Several reports have suggested that the pumping activity of the
      multidrug resistance gene 1 (MDR1)-encoded multidrug transporter P-glycoprotein
      (PGP) is enhanced by a PKC-mediated phosphorylation. It was shown here that
      bryostatin 1 was a potent modulator of multidrug resistance in two cell lines
      over-expressing a mutant MDR1-encoded PGP, namely KB-C1 cells and HeLa cells
      transfected with an MDR1-V185 construct (HeLa-MDR1-V185) in which glycine at
      position 185 (G185) was substituted for valine (V185). Bryostatin 1 is not able
      to reverse the resistance of cells over-expressing the wild-type form (G185) of
      PGP, namely CCRF-ADR5000 cells and HeLa cells transfected with a MDR1-G185
      construct (HeLa-MDR1-G185). Treatment of HeLa-MDR1-V185 cells with bryostatin 1
      was accompanied by an increase in the intracellular accumulation of rhodamine
      123, whereas no such effect could be observed in HeLa-MDR1-G185 cells. HeLa-MDR1
      V185 cells expressed the PKC isoforms alpha, delta and zeta. Down-modulation of
      PKC alpha and delta by 12-O-tetradecanoylphorbol-13-acetate (TPA) did not affect
      the drug accumulation by bryostatin 1. Bryostatin 1 depleted PKC alpha completely
      and PKC delta partially. In HeLa-MDR1-V185 cells, short-term exposure to
      bryostatin 1, which led to a PKC activation, was as efficient in modulating the
      pumping activity of PGP as long-term exposure leading to PKC depletion.
      Bryostatin 1 competed with azidopine for binding to PGP in cells expressing the
      MDR1-V185 and MDR1-G185 forms of PGP. It is concluded that bryostatin 1: i)
      interacts with both the mutated MDR1-V185 and the wild-type MDR1-G185; ii)
      reverses multidrug resistance and inhibits drug efflux only in PGP-V185 mutants;
      and iii) that this effect is not due to an interference of PKC with PGP. For gene
      therapy, it is important to reverse the specific resistance of a mutant in the
      presence of a wild-type transporter and vice versa. Our results show that it is
      possible to reverse a specific mutant PGP.

PMID- 9774149
TI  - Co-regulation of antigen-specific T lymphocyte responses by type I and type II
      cyclic AMP-dependent protein kinases (cAK).
AB  - While a differential sensitivity to cyclic AMP (cAMP)-mediated signaling between
      Th1 and Th2 cells has been hypothesized, differential activity of downstream
      signaling through cAMP-dependent protein kinase (cAK) isoforms remains
      unexplored. We herein report the effects of type 1- and type 2-specific cAK
      agonists and antagonists on proliferative responses and cytokine generation from
      ragweed-driven peripheral blood mononuclear cells (PBMCs) and Amb a 1-specific
      Th1 and Th2 clones. Rp-8-Cl- and Rp-8-CPT-cAMP were utilized as single agent
      antagonists of cAKI and cAKII, respectively; 8-AHA-cAMP, with and without 8-PIP
      cAMP, and 8-CPT-cAMP, with and without 6-Bnz-cAMP, were used as synergistic
      agonist pairs specific for the cAKI and cAKII, respectively. Activation of either
      cAKI or cAKII individually was ineffective in down-regulating proliferative
      responses of PBMCs or T cell clones; concentration-response curves for the Th1
      and Th2 clones were identical. Moreover, inhibition of either cAKI or cAKII
      individually was ineffective in overcoming the down-regulatory effects of
      phosphodiesterase inhibition. Activation of either cAKI or cAKII individually was
      ineffective in down-regulating proinflammatory cytokine generation from T cell
      clones (interleukin-4 from Th2; interferon-gamma from Th1). However, concurrent
      activation of both cAKI and cAKII produced down-regulatory effects equivalent to
      those of the phosphodiesterase inhibitor on both proliferation and cytokine
      generation. These data suggest a critical role for concurrent activation of cAKI
      and cAKII in the functional efficacy of antigen-driven downstream signaling due
      to elevations of intracellular cAMP and argue against differential regulation of
      Th1 and Th2 responses by cAK subtypes.

PMID- 9774150
TI  - Inhibition of NADPH-cytochrome P450 reductase and glyceryl trinitrate
      biotransformation by diphenyleneiodonium sulfate.
AB  - We reported previously that the flavoprotein inhibitor diphenyleneiodonium
      sulfate (DPI) irreversibly inhibited the metabolic activation of glyceryl
      trinitrate (GTN) in isolated aorta, possibly through inhibition of vascular NADPH
      cytochrome P450 reductase (CPR). We report that the content of CPR represents
      0.03 to 0.1% of aortic microsomal protein and that DPI caused a concentration-
      and time-dependent inhibition of purified cDNA-expressed rat liver CPR and of
      aortic and hepatic microsomal NADPH-cytochrome c reductase activity. Purified CPR
      incubated with NADPH and GTN under anaerobic, but not aerobic conditions formed
      the GTN metabolites glyceryl-1,3-dinitrate (1,3-GDN) and glyceryl-1,2-dinitrate
      (1,2-GDN). GTN biotransformation by purified CPR and by aortic and hepatic
      microsomes was inhibited > 90% after treatment with DPI and NADPH. DPI treatment
      also inhibited the production of activators of guanylyl cyclase formed by hepatic
      microsomes. We also tested the effect of DPI on the hemodynamic-pharmacokinetic
      properties of GTN in conscious rats. Pretreatment with DPI (2 mg/kg)
      significantly inhibited the blood pressure lowering effect of GTN and inhibited
      the initial appearance of 1,2-GDN (1-5 min) and the clearance of 1,3-GDN. These
      data suggest that the rapid initial formation of 1,2-GDN is related to mechanism
      based GTN biotransformation and to enzyme systems sensitive to DPI inhibition. We
      conclude that vascular CPR is a site of action for the inhibition by DPI of the
      metabolic activation of GTN, and that vascular CPR is a novel site of GTN
      biotransformation that should be considered when investigating the mechanism of
      GTN action in vascular tissue.

PMID- 9774152
TI  - Inhibition of gastric mucosal prostaglandin synthetase activity by
      mercaptomethylimidazole, an inducer of gastric acid secretion--plausible
      involvement of endogenous H2O2.
AB  - We have reported earlier that mercaptomethylimidazole (MMI), an antithyroid drug
      of thionamide group, induces gastric acid secretion at least partially through
      the liberation of histamine, sensitive to cimetidine. Now, we show that the drug
      has a significant inhibitory effect on the cyclooxygenase and peroxidase activity
      of the prostaglandin (PG) synthetase of the gastric mucosal microsomal
      preparation. The effect can also be mimicked by low concentrations of H2O2. While
      studying the possible intracellular effect of MMI on acid secretion, a cell
      fraction (F3) enriched in parietal cell was isolated by controlled digestion of
      the mucosa with protease. This cell fraction is activated by MMI as measured by
      increased O2 consumption. The activation is sensitive to omeprazole, a proton
      pump inhibitor, indicating that the activation is due to increased acid secretion
      by MMI. MMI was also found to directly inhibit the peroxidase activity of the F3
      cell fraction and may thus increase the intracellular level of H2O2. The
      cyclooxygenase activity of the PG synthetase of the F3 cell fraction is also
      inhibited by MMI and the effect can be reproduced by low concentrations of H2O2.
      Both MMI and H2O2 can also inhibit the peroxidase activity of the PG synthetase.
      We suggest that in addition to the activation of the parietal cell by MMI
      possibly through endogenous H2O2, MMI induces acid secretion in vivo by
      inactivating the PG synthetase thereby inhibiting the biosynthesis of PG and
      removing its inhibitory influence on acid secretion so that the histamine
      released by MMI can stimulate acid secretion with maximum efficiency.

PMID- 9774151
TI  - Biochemical and connective tissue changes in cyclophosphamide-induced lung
      fibrosis in rats.
AB  - The present investigation was designed to characterize the biochemical and
      connective tissue components and to correlate the significance of morphological
      and biochemical perturbations in cyclophosphamide (CP)-induced lung fibrosis in
      rats. Lung fibrosis was induced in male Wistar rats by intraperitoneal injection
      of 20 mg/100 g body weight of CP, and their pneumotoxic derangements were
      characterized during an early destructive phase followed by a proliferative and
      synthetic phase. Serum angiotensin-converting enzyme (ACE) activity was higher in
      CP-treated rats at days 2, 3, 5, 7, and 11, but there was a significant decrease
      in lung ACE activity during the same time period. Elevated levels of beta
      glucuronidase activity were observed in the lung lavage fluid of CP-administered
      rats days 2, 3, 5, and 7. Lung myeloperoxidase activity was higher in CP rats. Of
      significance was the presence of collagenase and collagenolytic cathepsin in the
      lavage fluid of CP rats, when compared with the barely detectable levels in
      controls. A similar increase in these enzyme activities was also noticed in the
      lung tissue of CP rats during the same experimental period. Lavage fluid
      hydroxyproline content was higher in CP rats when compared with controls.
      Similarly, lung protein and DNA levels were elevated significantly after
      treatment with CP. The pulmonary histamine and serotonin contents were
      significantly higher in CP rats. The incorporation of [3H]thymidine into lung
      total DNA, [3H]proline into lung hydroxyproline, and [35S]sulphate into lung
      glycosaminoglycan, measured as indicators of lung DNA, collagen, and
      glycosaminoglycan synthesis, respectively, was also higher in CP groups.
      Increased levels of hydroxyproline, elastin, hexosamine, total hexose, fucose,
      sialic acid, and uronic acid in the lungs of rats 14, 28, and 42 days after CP
      insult were characterized as biomarkers of CP-induced interstitial changes. These
      findings indicate that CP-induced lung fibrosis results in alterations not only
      in collagen synthesis and accumulation, but also in glycosaminoglycan and
      glycoprotein content.

PMID- 9774153
TI  - Reduced nicotinamide adenine dinucleotide phosphate-diaphorase activity in the
      paraventricular nucleus of the rat hypothalamus is modulated by estradiol.
AB  - Based on previous studies demonstrating that reduced nicotinamide adenine
      dinucleotide phosphate (NADPH)-diaphorase (ND) activity is modulated by estradiol
      and the discovery of a new subtype of estrogen receptor highly expressed in the
      paraventricular nucleus of the hypothalamus (PVN), a possible estrogen influence
      on this activity was investigated in the neuronal populations (magno- and
      parvicellular) of this nucleus. Cryostat sections were cut and processed for the
      histochemical detection of the ND activity. Following ovariectomy (14 days),
      numerical data displayed a slight decrease in the number of ND-neurons,
      especially in the posterior magnocellular and the medial parvicellular
      subdivisions, which was reversed after daily treatment with estradiol benzoate.
      Administration of estradiol benzoate to male rats (14 days) induced a significant
      increase (P < 0.05) in the number of ND-neurons, mainly at the level of the
      posterior magnocellular subdivision. These data indicate that paraventricular ND
      neurons are influenced by estradiol.

PMID- 9774155
TI  - Horizontal cells of the rat retina show choline acetyltransferase- and vesicular
      acetylcholine transporter-like immunoreactivities during early postnatal
      developmental stages.
AB  - We examined cholinergic neurons in the developing rat retina; an antiserum
      against choline acetyltransferase (ChAT) and an antiserum against vesicular
      acetylcholine transporter (VAChT) were used. From postnatal day 4 (P4) to P10,
      ChAT- and VAChT-like immunoreactivities were seen in cells which were located in
      the outer part of the inner nuclear layer. These cells had relatively large cell
      bodies and extended several transversely oriented processes. Double fluorescence
      immunohistochemistry using an antiserum against calbindin D-28K, a specific
      marker for the horizontal cells, revealed that all of ChAT- or VAChT-labeled
      cells showed calbindin D-28K-like immunoreactivity. These cells were no longer
      immunostained after P11. Thus, acetylcholine was considered to be transiently
      synthesized in the horizontal cells during early postnatal developmental stages
      in the rat retina.

PMID- 9774154
TI  - Stimulation of the neostriatum induces jaw-opener muscle activity, but not jaw
      closer muscle activity: an electromyographic study in the rat.
AB  - Microstimulation was carried out at 36 sites in the dorsal striatum in lightly
      anesthetized rats. Only at two sites, microstimulation of 40 microA induced a
      considerable EMG activity in the jaw-opener (anterior digastric muscle). No
      activity was evoked in the jaw-closers (masseter and temporalis muscles). The
      effective sites were confirmed to be localized in a small central region of the
      striatum at a level corresponding to the caudal end of the anterior commissure.
      The effect was ascribed to excitation of a small cluster of striatal neurons,
      rather than to antidromic activation of cerebral cortical neurons through their
      axons within the striatum. (1) The effect was abolished after destruction of
      neurons in the striatal region by injecting kainic acid. (2) The effect was not
      influenced by ablation of the neocortex. (3) Microinjection of kainic acid into
      the striatal region also induced the similar muscle activity in the jaw-opener,
      but not in the jaw-closers.

PMID- 9774156
TI  - Scopolamine impairs memory recall in Octopus vulgaris.
AB  - The involvement of the central cholinergic system in predatory performance, and
      on the recall of individual and observational memory in Octopus vulgaris was
      studied by treating the animals with the muscarinic antagonist scopolamine (2
      mg/kg). The absence of the effects of the injection of scopolamine on blood
      circulation was also checked. Scopolamine did not affect the ability of octopuses
      to prey on live crabs. However, it interfered significantly with memory recall.
      In fact, the ability to solve the jar problem was impaired within the first hour
      after injection (short-term effects) and was only partially recovered after 24 h
      (long-term). Moreover, both individual and observational learning of a visual
      discrimination were significantly reduced at the short- and long-term testing.
      These results support a role of the cholinergic system in the processes of memory
      recall of O. vulgaris.

PMID- 9774157
TI  - Inhibition of apamin-sensitive calcium dependent potassium channels facilitate
      the induction of long-term potentiation in the CA1 region of rat hippocampus in
      vitro.
AB  - Using field potential recording in the CA1-region of rat hippocampal slices we
      investigated the effect of apamin; a specific antagonist of small conductive
      calcium activated potassium channels on long-term potentiation (LTP). The
      experiments revealed that LTP of excitatory postsynaptic potentials induced by a
      single 100 Hz tetanization was intensified by extracellular application of apamin
      in a concentration range of 1-200 nM. No effects of apamin on LTP induced by
      triple 100 Hz tetanization were seen. We conclude that the positive modulation of
      LTP by apamin is effective in a nanomolar concentration range and dependent upon
      the employed tetanization. Because it has been shown that apamin-binding sites
      are affected by learning disorders including Alzheimer's disease, our finding
      suggests that changes in the sensitivity to apamin may result in memory
      disorders.

PMID- 9774158
TI  - Heparin inhibits induction of nitric oxide synthase by cytokines in rat brain
      microvascular endothelial cells.
AB  - The inflammatory reaction following ischemic brain injury involves bioactive
      mediators released mainly from leukocytes. The aim of this in vitro-study was to
      evaluate possible modulatory actions of heparin on nitric oxide synthesis induced
      by proinflammatory cytokines. Rat microvascular brain endothelial cells were
      isolated from adult rat brains and treated with interferon-gamma (IFN-gamma) and
      interleukin-1beta (IL-1beta) with or without heparin. The expression of inducible
      nitric oxide synthase (iNOS) mRNA and the iNOS protein activity was analyzed by
      reverse transcription polymerase chain reaction (RT-PCR) and Griess reagent,
      respectively. Heparin in a dose-dependent manner attenuated the increase in iNOS
      expression and NO release after cytokine activation. Thus, in addition to its
      anticoagulatory effect, heparin may also be effective in the prevention of
      inflammatory reaction after cerebral ischemia.

PMID- 9774159
TI  - Functional asymmetries of crossed and uncrossed medial olivocochlear efferent
      pathways in humans.
AB  - In a previous study, a peripheral auditory asymmetry in right-handers was found.
      The activity of the uncrossed medial olivocochlear efferent pathway has been
      shown to be more effective in the right than in the left ear. Our aim was to
      compare right and left medial olivocochlear inhibition during contralateral,
      ipsilateral and binaural ear stimulation with a broad band noise, in order to
      better localize this asymmetry. Uncrossed pathway asymmetry was confirmed and the
      crossed pathway showed a reverse asymmetry: a left ear advantage. These results
      are in accordance with the assumption that the medial superior olivary complex is
      the locus of the asymmetry observed. As this nuclear complex receives central
      efferents, the peripheral auditory asymmetry may be related to the well-known
      cortical asymmetry.

PMID- 9774160
TI  - Effects of movement direction upon kinematic characteristics of vertical arm
      pointing movements in man.
AB  - Vertical arm pointing movements in two directions (upwards and downwards),
      imposing two different loads (unload and 0.5 kg) and speeds (normal and fast)
      have been studied in six subjects. Movements were recorded using an
      optoelectronic system. Data analysis concentrated upon finger-tip kinematics.
      Significant effects of movement direction were recorded upon velocity profiles.
      The acceleration time, computed relative to total movement time, was greater for
      downward movements than for upward movements. In contrast however, no effects of
      load or speed were observed. Movement time was not affected by movement direction
      or load, for both speeds tested. These results suggest different planning
      processes, for movements with and against gravity and indicate that gravitational
      force influences the processes controlling movement execution.

PMID- 9774161
TI  - Topographic study of human event-related potentials using a task requiring mental
      rotation.
AB  - Event-related potentials (ERPs) were recorded during a mental rotation task that
      required subjects to determine whether two stimuli presented in turn had the same
      shape regardless of any difference in orientation. This task consisted of two
      conditions: the control condition, when the two stimuli presented were identical,
      requiring only recognition, and the experimental condition that required
      recognition following mental rotation. We hypothesized that differences between
      ERPs recorded during the control and experimental conditions were
      neurophysiologically correlated with mental rotation. In the experimental
      condition, a marked negative component arose about 430 ms after the second
      stimulus. The statistically significant difference between the negative
      components of the two conditions was maximal over the right frontocentral region,
      suggesting that mental rotation processing is a right hemisphere dominant
      function.

PMID- 9774162
TI  - Effect of pregnane steroids on electrocortical activity and somatosensory evoked
      potentials in fetal sheep.
AB  - The effect of infusing the neuroactive steroids pregnanolone and iso-pregnanolone
      on somatosensory evoked potentials (SEP) and electrocortical (ECoG) activity was
      studied in unanaesthetised fetal sheep, 130-135 days gestation. Intravenous
      infusion of pregnanolone (6 mg/kg per h) significantly increased the proportion
      of high voltage ECoG (56.1+/-4.8% vs. control 43.5+/-3.2%, P < 0.05), and
      decreased low voltage ECoG (43.9+/-4.8% vs. control 56.6+/-3.2%, P < 0.05).
      Pregnanolone treatment decreased the amplitude of the N25 peak of the SEP (89.9+/
      2.8% of control, P < 0.05) evoked following stimulation of the skin of the upper
      lip. In contrast, iso-pregnanolone treatment had no effect on ECoG activities, or
      on the amplitude and latency of peaks in the SEP. We conclude that 3alpha-hydroxy
      pregnane steroids are active at GABA(A) receptors in fetal sheep and can modulate
      sleep/wake activity before birth.

PMID- 9774163
TI  - Eye-head coordination for the steering of locomotion in humans: an anticipatory
      synergy.
AB  - We investigated head and gaze orientation in six healthy volunteers walking along
      90 degrees corner trajectories, both at light and with eyes closed. We found that
      head and eyes systematically deviated toward the future direction of the curved
      trajectory. Anticipation lead was about 1 s. Strikingly, the same behaviour was
      observed in darkness. In backward (BW) locomotion along the trajectory (from end-
      to start-point), gaze deviated toward the opposite direction, such that the
      forward locomotor pattern did not appear time-reversed. Orienting movements
      displayed higher amplitude, reproducibility and time lead in the forward (FW)
      direction at light. We suggest that anticipatory orienting synergies belong to
      the behavioural repertoire of human navigation and may reflect the need to
      prepare a stable reference frame for intended action.

PMID- 9774164
TI  - Mossy fibre innervation is not required for the development of kainic acid
      toxicity in organotypic hippocampal slice cultures.
AB  - The glutamate analogue kainic acid (KA) generates convulsions when applied
      systemically or directly into the brain and produces lesions comparable to those
      seen in Ammon's horn sclerosis, observed in many patients with temporal lobe
      epilepsy. The neurotoxic actions of KA in-vivo appear to be mediated by a
      combination of direct effects on neurons and indirect effects mediated by
      seizures. Understanding the contribution of both direct and indirect effects of
      KA towards neuronal cell death is important for elucidating excitotoxic
      mechanisms, which may represent a common final pathway in a variety of
      neurodegenerative disorders including stroke, traumatic brain injury and
      epilepsy. We have investigated the effects of mossy fibre innervation on the
      development of KA toxicity in organotypic hippocampal slice cultures in order to
      assess the role of this input pathway on the specific toxicity of KA toward CA3
      pyramidal neurones in vitro.

PMID- 9774165
TI  - The endogenous cannabinoid anandamide, but not the CB2 ligand
      palmitoylethanolamide, prevents the viscero-visceral hyper-reflexia associated
      with inflammation of the rat urinary bladder.
AB  - Anandamide, an endogenous ligand at the CB1 cannabinoid receptor and
      palmitoylethanolamide (a putative endogenous ligand at the CB2 receptor) have
      both been shown to possess anti-hyperalgesic properties in models of somatic and
      visceral inflammation. In the turpentine-inflamed rat urinary bladder a reversal
      of the inflammation-associated viscero-visceral hyperreflexia (VVH) was observed
      when the cannabinoids were administered 135 min after the induction of
      inflammation. Therefore, in this study we determined the efficacy of these two N
      acylethanolamides in the prevention of VVH in the same model, using a
      prophylactic dosing regimen. Palmitoylethanolamide did not prevent the VVH (in
      the dose range 10-30 mg/kg, i.a), but anandamide attenuated the response in a
      dose related manner, with a threshold of 25 mg/kg (i.a). These findings provide
      further support for an acute anti-nociceptive and anti-hyperalgesic role for CB1
      receptor agonists, with CB2 agonist effects only becoming important once the
      effects of inflammation are established.

PMID- 9774166
TI  - Participation of the prefrontal cortices in prospective memory: evidence from a
      PET study in humans.
AB  - Prospective memory is a memory feature in humans which involves activities for
      remembering to do something in the future. The present study provides functional
      neuroanatomy of prospective memory for the first time. We used positron emission
      tomography (PET) and found several localized brain activations in relation to a
      prospective memory task required to retain and remember a planned action while
      performing an ongoing routine activity. Activations were identified in the right
      dorsolateral and ventrolateral prefrontal cortices, the left frontal pole and
      anterior cingulate gyrus, the left parahippocampal gyrus, and midline medial
      frontal lobe. We attributed these activations to several cognitive processes
      involved in prospective memory, such as holding an intention toward future
      behavior, checking target items within presented stimuli, and dividing attention
      between the planned action and the routine activity.

PMID- 9774167
TI  - Spike discharge regularity of vestibular neurons in labyrinthectomized guinea
      pigs.
AB  - Single unit activity of second-order vestibular neurons was recorded in alert
      guinea pigs. Here, we compared the spike discharge regularity (measured by
      calculating the coefficient of variation (CV)) of neurons from control animals
      with those from animals labyrinthectomized 1 week before. The mean CV (+/-SD)
      were the same in both groups (0.72+/-0.43 vs. 0.70+/-0.39). Furthermore, in both
      groups, the CV was related to the resting rate (RR) according to the same law (CV
      = 4/square root of RR). Because the discharge of a neuron is more regular when it
      is due to a pacemaker activity than when it is due to the synaptic drive, we
      conclude that restoration in the firing rate after labyrinthectomy is due to
      increase in the synaptic drive rather than to increase in the (intrinsic)
      pacemaker activity.

PMID- 9774168
TI  - The effects of modafinil on striatal, pallidal and nigral GABA and glutamate
      release in the conscious rat: evidence for a preferential inhibition of striato
      pallidal GABA transmission.
AB  - The effects of the anti-narcoleptic drug modafinil (30-300 mg/kg i.p.) on GABA
      and glutamate release were evaluated in the basal ganglia of the conscious rat,
      by using the microdialysis technique. Modafinil (100 mg/kg) inhibited striatal
      (85+/-4% of basal values) and pallidal (85+/-2%) GABA release without influencing
      local glutamate release. At the highest dose (300 mg/kg), modafinil induced a
      further reduction of pallidal (75+/-2%) but not striatal (82+/-7%) GABA release
      and increased striatal (134+/-11%) but not pallidal glutamate release. On the
      contrary, in the substantia nigra modafinil reduced GABA release only at the 300
      mg/kg dose (59+/-5%) without affecting glutamate release. The preferential
      reduction in striato-pallidal GABA release at the 100 mg/kg dose of modafinil
      suggests that modafinil may be useful in the treatment of Parkinsonian diseases.

PMID- 9774169
TI  - Beta-amyloid (1-42) peptide impairs blood-brain barrier function after
      intracarotid infusion in rats.
AB  - The effects of intracarotid infusions of beta-amyloid (1-42) peptide was studied
      on the permeability of brain vessels. Using a quantitative Evans blue method a
      dose-dependent increase of brain tissue albumin content was established following
      intracarotid injections of the peptide. Cerebral vessels of increased
      permeability were also demonstrated with a vital 'staining' technique. Lectin
      histochemistry revealed an almost complete abolition of specific lectin binding
      sites of affected endothelial cells. The findings indicate a significant
      deterioration by beta-amyloid (1-42) peptide of blood-brain barrier function and
      suggest that this may result from endothelial damage. It is assumed that altered
      permeability of cerebral vessels may be involved in the development of brain
      pathologies associated with Alzheimer's disease.

PMID- 9774170
TI  - Effect of dietary lipid on gamma-glutamyl transferase-positive foci during
      hepatocarcinogenesis in rats.
AB  - The effect of dietary lipid on gamma-glutamyl transferase-positive (GGT-positive)
      foci was investigated. Female Sprague-Dawley rats were dosed with
      diethylnitrosamine (15 mg/kg) at 24 h of age. After weaning, they were fed
      nutritionally complete semipurified diets for 3 months. Rats fed 15% corn oil had
      significantly lower hepatic phospholipid eicosapentaenoate and docosahexaenoate
      than rats fed 7.5% corn oil plus 7.5% fish oil, 5% corn oil plus 10% fish oil (P
      < 0.05). However, rats fed 15% corn oil had significantly greater hepatic
      phospholipid arachidonate than rats fed the other two diets (P < 0.05),
      suggesting that n-3 polyunsaturated fatty acids were incorporated into hepatic
      phospholipid at the expense of n-6 polyunsaturated fatty acids. Hepatic PGF2alpha
      content was significantly greater in rats fed 15% corn oil than in rats fed the
      other two diets (P < 0.05). Rats fed fish oil had significantly lower hepatic
      vitamin E content than rats fed corn oil (P < 0.05). Hepatic lipid peroxidation
      (TBARS) tended to increase with increased dietary fish oil (P < 0.05). Dietary
      lipid did not influence GGT-positive foci area or number. In conclusion, dietary
      lipid affected hepatic PGF2alpha production, however, showed no effect on GGT
      positive foci area and number. This may suggest that PGF2alpha is not the
      underlying mechanism for GGT-positive foci during hepatocarcinogenesis.

PMID- 9774171
TI  - Increased production of TNF-alpha and decreased levels of dienoic eicosanoids, IL
      6 and IL-10 in mice fed menhaden oil and juniper oil diets in response to an
      intraperitoneal lethal dose of LPS.
AB  - Eicosapentaenoic acid (EPA) and the non-methylene interrupted fatty acids (NMIFA)
      displace arachidonic acid (AA: 20:4omega6 -5,8,11,14) in the membrane
      phospholipids. Unlike EPA (20:5omega3 -5,8,11,14,17), the NMIFA (20:3omega6 
      5,11,14 and 20:4omega3 -5,11,14,17) lacking the delta-8 double bond are not
      substrates for the formation of eicosanoids. For 20 days, the mice were fed diets
      containing 5wt% dietary fats from various sources. The magnitudes in the
      production of eicosanoids and cytokines produced in response to an
      intraperitoneal injection of endotoxin in mice fed menhaden fish oil (MO) diets
      enriched with EPA were compared with those maintained on juniper oil (JO)
      containing NMIFA or on safflower oil (SO), a major source of the AA precursor,
      linoleic acid. The levels of PGE2, 6-keto-PGF1alpha and TXB2 were markedly lower
      (P < 0.01) in animals fed either MO or JO diets compared to the controls. The
      plasma levels of tumor necrosis factor (TNF)-alpha were significantly higher (P <
      0.05) with a concomitant decrease of interleukin (IL)-6 and of IL-10 in mice fed
      MO or JO diets (P < 0.01) compared to those fed SO diet. These data suggest that
      the effects of consuming NMIFA of JO despite their inability to form eicosanoids
      are similar to those of feeding EPA which forms biologically active alternate
      metabolites.

PMID- 9774172
TI  - Comparison of the effects of nitric oxide and peroxynitrite on the 12
      lipoxygenase and cyclooxygenase metabolism of arachidonic acid in rabbit
      platelets.
AB  - The effects of a new type of nitric oxide (NO)-releasing compound, 1-hydroxyl-2
      oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC7), and peroxynitrite
      (ONOO-) on the formation of 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE),
      thromboxane (TX) B2 and 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) from
      exogenous arachidonic acid in washed rabbit platelets have been compared. At
      concentrations of 5 microM and below, NOC7 inhibited 12-HETE formation (56.5
      98.8% inhibition). Moreover, NOC7 inhibited TXB2 and HHT formation at
      concentrations ranging from 5 to 20 microM (TXB2, 62.2-88.1% inhibition; HHT,
      11.6-62.2% inhibition). ONOO- had little or no effect on the production of these
      three metabolites at concentrations of up to 50 microM. Experiments utilizing a
      new class of NO antidote, carboxy-2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl
      3-oxide, revealed that the observed effects of NOC7 are caused by NO. The effects
      of NO were reversed by addition of the superoxide generating system (xanthine
      plus xanthine oxidase and catalase), indicating that superoxide is a vital
      modulator of the action of NO. These results suggest that NO, but not ONOO- (up
      to 50 microM), can be a potent dual inhibitor of the 12-lipoxygenase and
      cyclooxygenase activities in platelets and that superoxide is an important
      regulator of the action of NO.

PMID- 9774173
TI  - Phosphatidic acid effects on cytosolic calcium and proliferation in osteoblastic
      cells.
AB  - Our previous studies show that epidermal growth factor (EGF) stimulates
      phospholipase D (PLD)-induced phosphatidic acid (PA) formation in rat calvarial
      osteoblastic cells. This study investigated the effects of PA on cytosolic
      calcium ([Ca2+]i) and proliferation, and the possible involvement of the PLD
      pathway in EGF effects on [Ca2+]i and proliferation in rat calvarial osteoblastic
      cells. PA markedly increased [Ca2+]i. This response was unaffected by
      thapsigargin, which depletes [Ca2+]i pools, blocked by verapamil, a calcium
      channel blocker, and enhanced by propanolol, an inhibitor of PA-phosphohydrolase.
      PA also reduced the EGF dependent-[Ca2+]i increase by 60%, while a PLD inhibitor
      blocked these effects. Furthermore, PA significantly increased cell proliferation
      (P < 0.05) which was inhibited by verapamil and enhanced by H-7 (PKC inhibitor).
      The PLD inhibitor significantly (P < 0.05) reduced the EGF-induced increase in
      proliferation. In summary, PA stimulates rat calvarial osteoblastic cell
      proliferation and mobilization of [Ca2+]i using extracellular pools, and EGF's
      mitogenic effect on these cells requires activation of PLD.

PMID- 9774174
TI  - Structural requirements for arachidonylethanolamide interaction with CB1 and CB2
      cannabinoid receptors: pharmacology of the carbonyl and ethanolamide groups.
AB  - Analogs of arachidonylethanolamide (anandamide) were prepared to investigate the
      structural requirements for ligand binding to and activation of the CB1 and CB2
      cannabinoid receptors. The importance of the presence and the placement of the
      carbonyl was examined with analogs lacking the carbonyl or with the carbonyl
      amide order reversed. The presence and location of the carbonyl is essential for
      high-affinity binding to both cannabinoid receptor subtypes, and for
      determination of signal transduction via G-proteins. Methyl groups were
      substituted on the 1'- and 2'-positions of arachidonylethanolamide and the
      significance of chirality was examined. Stereochemical differences in the
      ethanolamide group influence the affinity for both cannabinoid receptor subtypes
      and the signal transduction capabilities of the methanandamide derivatives.

PMID- 9774175
TI  - Helicobacter pylori fatty acid cis 9,10-methyleneoctadecanoic acid increases
      [Ca2+]i, activates protein kinase C and stimulates acid secretion in parietal
      cells.
AB  - The effect of the Helicobacter pylori (H. pylori) fatty acid cis 9,10
      methyleneoctadecanoic acid (MOA) on gastric acid secretion was studied in
      isolated guinea-pig parietal cells. MOA (1 and 3 micromol/l) stimulated basal and
      enhanced histamine- and dibutyryl cyclic AMP-stimulated acid secretion in
      parietal cells. MOA increased intracellular free [Ca2+]i concentration in a
      concentration-dependent manner. The source of [Ca2+]i was extracellular as
      demonstrated by depletion of [Ca2+]i with EGTA. Furthermore, MOA caused
      activation of parietal cell protein kinase C (PKC). The effect of MOA upon PKC
      activation was [Ca2+]i-dependent but did not require phosphatidylserine as
      phospholipid co-factor. Similarly to the effect of diolein, MOA increased the
      stimulatory effect of phosphatidylserine at low [Ca2+]i concentrations. Treatment
      of parietal cells with MOA caused translocation of PKC from the cytosol to the
      membrane-associated cell fraction. We propose that MOA stimulates parietal cell
      acid secretion presumably by an increase of cytosolic free [Ca2+]i concentrations
      and PKC activation.

PMID- 9774176
TI  - Attenuation of oxidant-mediated endothelial cell injury with docosahexaenoic
      acid: the role of intracellular iron.
AB  - Previous studies have demonstrated that altering the fatty acid composition of
      porcine pulmonary artery endothelial cells (PAEC) significantly modulates their
      susceptibility to oxidative stimuli, e.g. H2O2. Based on observations that fatty
      acids also function to transport iron, an important catalyst for H2O2-mediated
      hydroxyl radical generation, we hypothesized that fatty acid-induced alterations
      in PAEC iron metabolism contribute to modulation of PAEC oxidant susceptibility.
      To test this hypothesis, PAEC were treated with culture medium supplemented with
      0.1 mM oleic (18:1), linolenic (18:3) or docosahexaenoic (22:6) acids or with an
      equivalent volume of ethanol vehicle for 3 h. After thorough washing and
      incubation in unsupplemented culture medium for 24 h, PAEC monolayers were
      subjected to additional studies. Supplementation with 22:6 attenuated lactate
      dehydrogenase (LDH) release from PAEC 2 h following treatment with 100 microM
      H2O2 for 30 min (% LDH release: ETOH-control = 7.9 +/- 1.6, 22:6-control = 5.9 +/
      0.9, ETOH-H2O2 = 26.4 +/- 4.2, 22:6-H2O2* = 16.2 +/- 2.9; *P < 0.05 vs ETOH
      H2O2). In a non-cellular system, 18:1 and 18:3 were more effective than their
      methyl ester derivatives or 22:6 at translocating iron from aqueous to
      hydrophobic environments. In contrast, only supplementation with 22:6
      significantly increased PAEC uptake of 57Fe and human umbilical vein endothelial
      cell (HUVEC) ferritin content, whereas none of the supplementation conditions
      altered PAEC catalytic iron measured with bleomycin. These novel observations
      indicate that specific fatty acids are capable of altering PAEC iron uptake and
      ferritin content thereby contributing to the understanding of the mechanisms by
      which fatty acids modulate the oxidant susceptibility of vascular endothelial
      cells.

PMID- 9774177
TI  - Hypoxic pulmonary vasoconstriction in pigs: role of endothelin-1, prostanoids and
      ATP-dependent potassium channels.
AB  - This study investigated the mechanisms that may contribute to the hypoxic
      pulmonary vasoconstriction and compared the effects of hypoxia on pulmonary and
      systemic vascular beds. Six anesthetized spontaneously breathing pigs inhaled a
      hypoxic mixture (10% O2 in air) in control conditions and after pre-treatment
      with Indomethacin (3 mg kg(-1) i.v.) to block the cyclooxygenase pathway. During
      hypoxia, the Indomethacin pre-treated pigs were given Cromakalim (80 microg kg(
      1) i.v.) to activate K+(ATP) channels. Bosentan (5 mg kg(-1) i.v.) was
      administered to block endothelin-1 receptors and then during hypoxia Cromakalim
      was administered as before. In all experimental conditions we recorded breathing
      pattern and vascular parameters: mean systemic and pulmonary arterial pressures;
      systemic and pulmonary vascular resistances; cardiac output; and heart rate.
      Vascular and respiratory responses to hypoxia were determined when PaO2 was
      reduced to 50 +/- 5 mmHg. The main finding was that in spontaneously breathing
      pigs, hypoxia induces pulmonary vasoconstriction and an increase in mean systemic
      arterial pressure, which are cyclooxygenase-independent. A role of endothelin-1
      appears in both vascular districts, but pulmonary vasoconstriction may also be
      due to ET-1-dependent inhibition of K+(ATP) channels.

PMID- 9774178
TI  - Influence of long-chain polyunsaturated fatty acids on oxidation of low density
      lipoprotein.
AB  - Enrichment of low density lipoprotein (LDL) with long-chain fatty acids, such as
      eicosapentaenoic acid (EPA; 20:5 n-3) and docosahexaenoic acid (DHA; 22:6 n-3)
      found in fish oil, is thought to increase its oxidative susceptibility although
      such an increase has not been clearly demonstrated. The purpose of this study was
      to determine the composition and fatty acid concentration of LDL obtained from
      postmenopausal women given a supplement of fish oil and relate these values to
      its oxidative susceptibility. Fish oil supplementation significantly increased
      LDL concentration of EPA (P = 0.0001) and DHA (P = 0.0001) and decreased that of
      linoleic acid P = 0.006). The concentration of free cholesterol, cholesterol
      ester, phospholipids and protein was unchanged while triglyceride concentration
      increased 8% (P = 0.02). Cu2+-mediated oxidation resulted in a shorter lag time,
      slower oxidation rate and similar concentrations of conjugated dienes of EPA/DHA
      enriched LDL than EPA/DHA-unenriched LDL. Stepwise multiple regression indicated
      that the primary predictor of oxidative susceptibility of LDL was linoleic acid,
      even after enrichment with EPA and DHA. The oxidation rate of EPA/DHA-unenriched
      LDL correlated with the cholesteryl ester concentration (P = 0.003) while that of
      EPA/DHA-enriched correlated with the concentration of phospholipids (P = 0.03).
      These data suggest that EPA/DHA-enriched LDL have decreased oxidative
      susceptibility and that surface lipids may mediate its rate of oxidation.

PMID- 9774179
TI  - Opioid receptor contributes to ischemic preconditioning through protein kinase C
      activation in rabbits.
AB  - Recent studies have reported that protection from ischemic preconditioning (PC)
      is blocked by the opioid receptor antagonist naloxone (NAL). We tested whether an
      opioid agonist could mimic PC in the rabbit heart, whether that protection
      involved protein kinase C (PKC) activation, and whether opioid receptors act in
      concert with other PKC-coupled receptors. Rabbit hearts were subjected to 30 min
      coronary occlusions and were reperfused for either 3 (in situ) or 2 (in vitro) h.
      Infarct size was determined by staining with triphenyltetrazolium chloride. In
      untreated in situ hearts 38.5+/-1.6% of the risk zone infarcted. PC with 5 min
      ischemia/10 min reperfusion significantly limited infarction to 12.7+/-2.9% (p <
      0.01). NAL infusion did not modify infarction (39.6+/-1.6%) in non-PC hearts, but
      blocked the effect of one cycle of PC (34.4+/-3.6% infarction). NAL, however,
      could not block cardioprotection when PC was amplified with 3 cycles of
      ischemia/reperfusion (9.9+/-1.4% infarction, p < 0.01 vs. control). Morphine
      could also mimic ischemic preconditioning, but only at a dose much higher than
      would be used clinically (3 mg/kg). In isolated hearts pretreatment with morphine
      (0.3 microM) significantly limited infarction to 9.3+/-1.2% (p < 0.01 vs. 32.0+/
      3.1% in controls). This cardioprotective effect of morphine could be blocked by
      either the PKC inhibitor chelerythrine (30.4+/-2.6% infarction) or NAL (34.0+/
      2.6% infarction). Neither chelerythrine nor NAL by itself modified infarction in
      non-PC hearts. NAL could not block protection from one cycle of PC in isolated
      hearts indicating that an intact innervation may be required for endogenous
      opioid production. Thus, opioid receptors, like other PKC-coupled receptors,
      participate in the triggering of PC in the rabbit heart.

PMID- 9774180
TI  - Equal reduction in infarct size by ethylisopropyl-amiloride pretreatment and
      ischemic preconditioning in the in situ rabbit heart.
AB  - Inhibition of Na+/H+ exchange with amiloride analogues has been shown to provide
      functional protection during ischemia and reperfusion and to reduce infarct size
      in isolated rat hearts. In rat hearts, treatment with ethylisopropyl-amiloride
      (EIPA, a selective Na+/H- exchange inhibitor) was additive to the protection
      afforded by ischemic preconditioning. In addition, such compounds have been
      demonstrated to reduce infarct size in in situ rabbit hearts. The aim of the
      present study was to determine to what extent preischemic treatment with EIPA
      could reduce infarct size in an in situ rabbit model of regional ischemia and
      reperfusion. We also wished to determine if this effect was additive to the
      infarct reducing effect of ischemic preconditioning. Anaesthetized, open chest
      rabbits, were subjected to 45 min of regional ischemia and 150 min of
      reperfusion. The risk zone was determined by fluorescent particles and infarct
      size was determined by TTC staining. Four groups were investigated: control,
      ischemic preconditioned (IP) (5 min of ischemia followed by 10 min reperfusion),
      EIPA (0.65 mg/kg iv given preischemically) and EIPA + IP. The main results
      expressed as percent infarction of the risk zone +/- S.E.M. for the different
      groups were: control 59.2+/-3.3% (n = 6), IP 16.3+/-2.1% (n = 6) (p < 0.001 vs.
      control), EIPA 16.9+/-4.1% (n = 5) (p < 0.001 vs. control), EIPA + IP 22.5 +/
      9.5% (n = 6) (p < 0.001 vs. control). IN CONCLUSION: EIPA, when administered
      prior to ischemia, caused a reduction in infarct size in the in situ rabbit heart
      which was similar to that seen with ischemic preconditioning, however, the effect
      was not additive to ischemic preconditioning.

PMID- 9774181
TI  - Loss of myocardial protection from ischemic preconditioning following chronic
      exposure to R(-)-N6-(2-phenylisopropyl)adenosine is related to defect at the
      adenosine A1 receptor.
AB  - Exogenously administered adenosine agonist will protect myocardium against
      infarction during ischemia. However, long-term exposure to adenosine agonists is
      associated with loss of this protection. To determine why this protection is
      lost, isolated, perfused rabbit hearts were studied after administration of R(-)
      N6-(2-phenylisopropyl)adenosine (PIA), 0.25 mg/h IP, for 3-4 days to intact
      animals. All hearts experienced 30 min of regional ischemia and 120 min of
      reperfusion. Control groups 1 and 2 were untreated. In group 1 this
      ischemia/reperfusion was the only intervention, whereas group 2 hearts were
      preconditioned with a cycle of 5 min global ischemia/10 min reperfusion preceding
      the 30 min regional ischemia. Groups 3-5 had been chronically exposed to PIA.
      Group 3 hearts had 1 preconditioning ischemia/reperfusion cycle before the
      prolonged ischemia. Group 4 received a 5 min infusion of 0.1 micromol/L
      phenylephrine in lieu of global ischemia, whereas group 5 was instead treated
      with 1 micromol/L carbachol. Infarct size averaged 32% of the risk zone in group
      1, whereas ischemic preconditioning limited infarction to 8.2% in group 2.
      Prolonged exposure of group 3 hearts to PIA resulted in the inability of
      preconditioning with 5 min global ischemia to protect (28.7+/-4.4% infarction).
      However, protection was restored by either phenylephrine, an agonist of alpha1
      adrenergic receptors which couple to Gq and stimulate PKC, or carbachol, an
      agonist of M2-muscarinic receptors which couple instead to Gi as do adenosine A1
      receptors (5.2+/-1.7% and 9.2+/-2.1% infarction, resp.). Therefore, cross
      tolerance to ischemic preconditioning develops after chronic PIA infusion. Since
      both the Gi and the PKC components of the preconditioning pathway were shown to
      be intact, tolerance must have been related to downregulation or desensitization
      of the A1 adenosine receptor.

PMID- 9774182
TI  - Rapid pacing-induced preconditioning is recaptured by farnesol treatment in
      hearts of cholesterol-fed rats: role of polyprenyl derivatives and nitric oxide.
AB  - We have previously shown that hypercholesterolemia leads to the loss of pacing
      induced preconditioning (PC), possibly due to the impairment of cardiac nitric
      oxide (NO) synthesis. It has been shown that excess exogenous cholesterol
      inhibits formation of several polyprenyl derivatives involved in signal
      transduction. In the present study, we examined whether PC and cardiac NO
      synthesis are restored by treatment with the key polyprenyl product, farnesol, in
      cholesterol-fed rats. Rats fed 2% cholesterol-enriched/control diet for 24 weeks
      were given i.p. 5 microM/kg farnesol/vehicle, respectively. An hour later, hearts
      were isolated and prepared for 'working' perfusion, then subjected to PC/non-PC
      protocols of 3 intermittent periods of pacing of 5 min duration at 10 Hz,
      followed by a 10 min coronary occlusion to test the effect of PC. PC increased
      ischemic aortic flow (AF) from its control value of 15.6+/-1.5 to 27.3+/-1.7
      mL/min (p < 0.05). PC was not observed in hearts obtained from
      hypercholesterolemic rats (AF: 15.7+/-1.2 mL/min), however, it reappeared in the
      farnesol-treated hypercholesterolemic group (AF: 31.8+/-3.4 mL/ min, p < 0.05).
      In tissue samples from the left ventricle, cholesterol-diet markedly decreased
      the intensity of the electron spin resonance spectra of NO obtained after in vivo
      spin trapping with Fe2+-diethyl-dithio-carbamate complex. Farnesol-treatment did
      not influence cardiac NO content in the cholesterol-fed or in the control group.
      These results show that the lost PC can be recaptured by farnesol-treatment in
      hypercholesterolemia, however, farnesol-treatment does not restore cardiac NO
      synthesis.

PMID- 9774183
TI  - Effect of ethanol on myocardial infarct size in a canine model of coronary artery
      occlusion-reperfusion.
AB  - This study was conducted to determine if elevated blood alcohol prior to acute
      coronary artery occlusion affects myocardial infarct size in an in vivo canine
      model. Seven pentobarbital anesthetized open-chest dogs received 10 min iv
      infusion of ethanol (0.08 g/kg/min). Ten min after ethanol, the left anterior
      descending coronary artery (LAD) was occluded distal to its first major branch
      for 60 min. The LAD was then reperfused for 5 h. Following electrically induced
      ventricular fibrillation, the area at risk of infarction was delineated with dye.
      The area of infarction was identified by staining with triphenyl tetrazolium
      chloride. Eleven untreated control experiments were also conducted. Mean blood
      ethanol concentration was 155+/-26 mg/dl just prior to LAD occlusion and 47+/-3
      mg/dl after 4 h reperfusion. Ethanol infusion had no effect on systemic
      hemodynamic variables during ischemia. In ethanol treated animals, the area at
      risk was 19.7+/-3.0% of the left ventricle, and the infarct size was 20.9 +/-4.8%
      of the area at risk. In control experiments, the area at risk was 23.0+/-4.1% of
      the left ventricle (p > 0.05), and the infarct size was 21.6+/-3.8% of the area
      at risk (p > 0.05). Collateral blood flow to ischemic region did not differ
      between the two groups, and the relationships between infarct size and collateral
      flow were similar for control and untreated hearts. Acute ethanol exposure prior
      to coronary artery occlusion and subsequent reperfusion does not affect
      myocardial infarct size in the heart of the anesthetized dog.

PMID- 9774185
TI  - Mechanism of hypoxic preconditioning in guinea pig papillary muscles.
AB  - Brief ischemia or hypoxia has been found to protect the heart against subsequent
      long-lasting ischemia and to improve contractile dysfunction as well to reduce
      cell necrosis and the incidence of lethal arrhythmias. This phenomenon, termed
      preconditioning (PC) has been demonstrated in different species. However, little
      is known about PC in guinea pigs. Moreover, electrophysiological changes
      underlying protection have not been studied so far in conjuntion with force
      recovery in a setting of PC. The aim of the study was to study PC in a guinea pig
      papillary muscle, using recovery of contractility after long hypoxic challenge as
      the main end-point of protection, and to investigate concomitant
      electrophysiological alterations. In guinea pig papillary muscle preparations
      contracting isometrically (paced at 2 Hz), transmembrane action potentials (AP)
      and developed force (DF) were recorded by conventional microelectrode technique
      and a force transducer. In addition, effective refractory periods (ERP) were
      determined. Hypoxia was induced by superfusion with 100% N2 (pO2 < 5 kPa) and
      pacing at 3,3 Hz. In the control group, long hypoxia lasted for 45 min and was
      followed by 30 min reoxygenation. In the PC group, muscles were subjected to 5
      min hypoxia followed by 10 min recovery prior to sustained hypoxia/reoxygenation.
      RESULTS: Long hypoxia induced a similar depression of DF in both, PC and control
      groups. However, a loss of contractile activity occured earlier in the PC group.
      AP duration and ERP decreased faster and were significantly shorter after PC.
      Upon reoxygenation, preconditioned muscles showed significantly better recovery
      of function (DF 86% of prehypoxic value vs. 36% in controls; p < 0,05). AP and
      ERP were completely restored in both, PC and control groups. Guinea pig papillary
      muscle can be preconditioned with a brief hypoxic challenge against contractile
      dysfunction upon long-lasting hypoxia/reoxygenation. Shortening of AP and loss of
      contractility occured more quickly during hypoxia and may participate in the
      protective effect of preconditioning. Possible mechanisms might involve
      facilitated opening of K(ATP)-dependent channels.

PMID- 9774184
TI  - Gene expression after short periods of coronary occlusion.
AB  - Brief periods of coronary occlusion render the affected myocardium more tolerant
      to the otherwise devastating effects of long coronary occlusion. Besides this
      phenomena, called ischemic preconditioning, short periods of ischemia cause a
      regional dysfunction, namely myocardial stunning. The molecular mechanisms of
      both syndromes are not very well understood. We therefore investigated the
      expression of genes which may be involved in cardioprotection or repair
      processes. Using our porcine model of ischemia and reperfusion we were able to
      show an induction of genes coding for transcription factors (proto-oncogenes),
      for proteins involved in repair processes (heat shock genes), for proteins
      implicated in the calcium homeostasis (calcium-handling genes) and for growth
      factors. We could show that the increased mRNA levels are due to an enhanced
      transcriptional activity and not to a prolonged half-life of the transcripts. The
      angiogenic growth factor vascular endothelial growth factor (VEGF) represents an
      exception. It exhibits--in addition to a HIF-motif (Hypoxia Inducible Factor) in
      its promoter/enhancer--a protein binding region in its 3' UTR which when occupied
      renders the mRNA more stable. However to what extent the expression of the
      distinct genes contributes to the cardioprotective effect of ischemic
      preconditioning or myocardial stunning can only be presumed. Increased mRNA
      stability can be confered via adenosine which is produced during ischemia by ATP
      breakdown. The demasking of unknown genes--via differential display reverse
      transcription polymerase chain reaction (DDRT-PCR)--should provide a more
      comprehensive view of the mechanisms underlying both processes.

PMID- 9774186
TI  - Characterisation and validation of a murine model of global ischaemia-reperfusion
      injury.
AB  - A specially designed Langendorff apparatus was constructed to allow perfusion of
      the isolated mouse heart. Hearts were randomised into groups to receive differing
      periods of global (zero flow) ischaemia or continuous perfusion (controls).
      During reperfusion, recovery of baseline force was recorded and perfusate
      collected for LDH assay (U/L/g wet weight). After 30 min reperfusion, hearts were
      stained with tetrazolium and planimetry performed to measure infarct size. Dose
      response relationships were demonstrated for all 3 end-points against duration of
      ischaemic insult. Functional recovery and enzyme leakage correlated well with
      infarct size (r = 0.77, p < 0.001 and r = 0.73, p < 0.001 respectively).
      Transgenic mice may now be used to study the effect of specific phenotypic
      changes on the pathogenesis of ischaemia-reperfusion injury using a reliable and
      reproducible technique.

PMID- 9774188
TI  - Differential electrophysiologic effects of global and regional ischemia and
      reperfusion in perfused rat hearts. Effects of Mg2+ concentration.
AB  - The effects of regional and global ischemia on cellular electrical activity and
      on arrhythmias induced by reperfusion were studied at different Mg2+
      concentrations (Mg2+o, 0, 1.2, and 4.8 mM) in perfused rat hearts. Surface
      electrograms and transmembrane potentials were recorded during control, 10 min of
      ischemia (perfusion arrest or coronary ligation), and reperfusion. Increasing
      Mg2+o from 0-4.8 mM decreased heart rate, did not alter action potential
      morphology, and had a strong antiarrhythmic action on reperfusion following
      coronary ligation. At low and normal Mg2+o, the incidence of tachyarrhythmias was
      between 70 and 80%. Global ischemia led to progressive atrioventricular block and
      the final ventricular beating rate was similar at all Mg2+o despite unequal
      initial values. The severity of arrhythmias was similar to that found after
      regional ischemia in Mg2+o = 0, but much lower at normal and high Mg2+o. The
      resting depolarization induced by coronary ligation decreased as Mg2+o was
      raised, but such a relation was not seen during global ischemia where the
      depolarization was less marked. The action potential duration did not vary with
      the ventricular rate between 160 and 380 beats per min but increased considerably
      when sinus rate was markedly slowed (40 to 80 bpm) by raising Mg2+o to 9.6 mM.
      Our data show that a high Mg2+o exerts a strong protection against reperfusion
      arrhythmias regardless of the type of ischemia. Modulation of the sinus rhythm by
      Mg2+ may contribute to its protective effect by decreasing K+o accumulation and
      Na+i loading during ischemia.

PMID- 9774187
TI  - Ischemic preconditioning in isolated perfused mouse heart: reduction in infarct
      size without improvement of post-ischemic ventricular function.
AB  - Genetically engineered mice provide an excellent tool to study the role of a
      particular gene in biological systems and will be increasingly used as models to
      understand the signal transduction mechanisms involved in ischemic
      preconditioning (IP). However, the phenomenon of IP has not been well
      characterized in this species. We therefore attempted to examine whether IP could
      protect isolated mouse heart against global ischemia/reperfusion (GI/R) injury.
      Thirty adult mice hearts were perfused at constant pressure of 55 mmHg in
      Langendorff mode. Following 20 min equilibration, the hearts were randomized into
      three groups (n = 10/each): (1) Control Group; (2) IP2.5 Group: IP with two
      cycles of 2.5 min GI + 2.5 min R; (3) IP5 Group: IP with 5 min GI + 5 min R. All
      hearts were then subjected to 20 min of GI and 30 min R (37 degrees C).
      Ventricular developed force was measured by a force transducer attached to the
      apex. Leakage of CK and LDH was measured in coronary efflux. Infarct size was
      determined by tetrazolium staining. Following sustained GI/R, infarct size was
      significantly reduced in IP2.5 (13.8+/-2.3%), but not in IP5 (20.1+/-4.0%), when
      compared with non-preconditioned control (23.6+/-3.8%) hearts. CK & LDH release
      was also reduced in both IP2.5 and IP5 groups. No significant improvement in post
      ischemic ventricular contractile function was observed in either IP groups. We
      conclude that IP with repetitive cycles of brief GI/R is able to reduce
      myocardial infarct size and intracellular enzyme leakage caused by a sustained
      GI/R in the isolated perfused mouse heart. This anti-necrosis cardioprotection
      induced by IP was not associated with the amelioration of post-ischemic
      ventricular dysfunction.

PMID- 9774189
TI  - Ischemic preconditioning and superoxide dismutase protect against endothelial
      dysfunction and endothelium glycocalyx disruption in the postischemic guinea-pig
      hearts.
AB  - The effect of ischemic preconditioning and superoxide dismutase (SOD) on
      endothelial glycocalyx and endothelium-dependent vasodilation in the postischemic
      isolated guinea-pig hearts was examined. Seven groups of hearts were used: group
      1 underwent sham aerobic perfusion; group 2 was subjected to 40 min global
      ischemia without reperfusion; group 3, 40 min ischemia followed by 40 min
      reperfusion; group 4 was preconditioned with three cycles of 5 min global
      ischemia followed by 5 min of reperfusion (IPC), prior to 40 min ischemia; group
      5 was subjected to IPC prior to standard ischemia/ reperfusion; group 6 underwent
      standard ischemia/reperfusion and SOD infusion (150 U/ml) was begun 5 min before
      40 min ischemia and continued during the initial 5 min of the reperfusion period;
      group 7 was subjected to 80 min aerobic perfusion with NO-synthase inhibitor, L
      NAME, to produce a model of endothelial dysfunction independent from the
      ischemia/reperfusion. Coronary flow responses to acetylcholine (ACh) and sodium
      nitroprusside (SNP) were used as measures of endothelium-dependent and
      endothelium-independent vascular function, respectively. Reduction in coronary
      flow caused by NO-synthase inhibitor, L-NAME, served as a measure of a basal
      endothelium-dependent vasodilator tone. After completion of each experimental
      protocol, the hearts were stained with ruthenium red or lanthanum chloride for
      electron microscopy evaluation of the endothelial glycocalyx. While ischemia led
      only to a slightly flocculent appearance of the glycocalyx, in
      ischemia/reperfused hearts the glycocalyx was disrupted, suggesting that it is
      the reperfusion injury which leads to the glycocalyx injury. Moreover, the
      coronary flow responses to ACh and L-NAME were impaired, while the responses to
      SNP were unchanged in the ischemia/reperfused hearts. The disruption of the
      glycocalyx and the deterioration of ACh and L-NAME responses was prevented by
      IPC. In addition, the alterations in the glycocalyx and the impairment of ACh
      responses were prevented by SOD. The glycocalyx appeared to be not changed in the
      hearts subjected to 80 min aerobic perfusion with L-NAME. IN CONCLUSION: (1) the
      impairment of the endothelium-dependent coronary vasodilation is paralleled by
      the endothelial glycocalyx disruption in the postischemic guinea-pig hearts; (2)
      both these changes are prevented by SOD, suggesting the role of free radicals in
      the mechanism of their development; (3) both changes are prevented by IPC. We
      hypothesize, therefore, that alterations in the glycocalyx contribute to the
      mechanism of the endothelial dysfunction in the postischemic hearts.

PMID- 9774190
TI  - Role of H2O2 in changing beta-adrenoceptor and adenylyl cyclase in ischemia
      reperfused hearts.
AB  - In view of the accumulation of H2O2 in the myocardium due to ischemia-reperfusion
      and changes in beta-adrenoceptor mechanisms in the ischemic-reperfused heart, we
      investigated the effects of H2O2 on the beta-adrenoceptor, G-protein and adenylyl
      cyclase complex. Rat hearts were perfused with 1 mM H2O2 for 10 min before
      isolating membranes for measuring the biochemical activities. The stimulation of
      adenylyl cyclase by different concentrations of isoproterenol was depressed upon
      perfusing hearts with H2O2. Both the affinity and density of beta1-adrenoceptors
      as well as the density of the beta2-adrenoceptors were decreased whereas the
      affinity of beta2-adrenoceptors was increased by H2O2 perfusion. Competition
      curves did not reveal any effect of H2O2 on the proportion of coupled receptors
      in the high affinity state. The basal as well as forskolin-, NaF- and Gpp(NH)p
      stimulated adenylyl cyclase activities were depressed by perfusing the heart with
      H2O2. Catalase alone or in combination with mannitol was able to significantly
      decrease the magnitude of alterations due to H2O2. The positive inotropic effect
      of 1 microM isoproterenol was markedly attenuated upon perfusing hearts with 200
      500 microM H2O2 for 10 min. These results suggest that H2O2 may depress the beta1
      adrenoceptor, Gs-proteins and catalytic subunit of the adenylyl cyclase enzyme
      and thus may play an important role in attenuating the beta-adrenoceptor linked
      signal transduction due to ischemia-reperfusion injury.

PMID- 9774192
TI  - Comparison of the effects of ACE inhibition with those of angiotensin II receptor
      antagonism on systolic and diastolic myocardial stunning in isolated rabbit
      heart.
AB  - The aim was to determine whether enalaprilat (0.08 mg/kg/min) or losartan (0.01
      mg/kg/min) administration before ischemia can improve postischemic systolic and
      diastolic dysfunction ('stunned myocardium') and attenuate the 'hyperfunction'
      phase at the beginning of reperfusion. An isolated isovolumic rabbit heart
      preparation was subjected to 15 min of ischemia followed by 30 min of reperfusion
      without (group 1) or with pretreatment with enalaprilat (group 2) or losartan
      (group 3). Left ventricular developed pressure and end-diastolic pressure
      (diastolic stiffness) were measured and the time constant of isovolumic
      relaxation (T, Tau) and the ratio between +dP/dt and -dP/dt were calculated. In
      comparison to the stunned group (group 1) both enalaprilat (group 2) and losartan
      (group 3) exerted a significant protective effect on postischemic recovery of
      contractile state and diastolic stiffness. Only enalaprilat attenuated the
      'hypercontractile' phase. However, both enalaprilat and losartan failed to
      improve myocardial relaxation. In summary, these data strongly suggest a direct
      deleterious action of the local renin-angiotensin system on ischemic myocardium
      and diminution of myocardial stunning with its successful blockade. Although, we
      can not exclude the possibility that bradykinin has some cardioprotective effect,
      these data suggest that angiotensin exacerbates myocardial injury.

PMID- 9774191
TI  - PBN spin trapping of free radicals in the reperfusion-injured heart. Limitations
      for pharmacological investigations.
AB  - Post-ischemic reperfusion causes cardiac dysfunction and radical-induced lipid
      peroxidation (LPO) detectable by ESR spin trapping. This study deals with the
      applicability of the spin trapping technique to pharmacological investigations
      during myocardial reperfusion injury. The use of the spin trap phenylbutylnitrone
      (PBN, 3 mM) in isolated rat hearts demonstrated the release of alkoxyl radicals
      (aN = 1.39 mT, aHbeta = 0.19 mT) formed particularly within the first 15 min of
      reperfusion following 30 min of ischemia. The decline of radicals, after 10 min
      of reperfusion, was accompanied by recovery of function in 80% of the hearts. The
      radical concentration in the coronary effluent (maximum after 7.5 min) was
      reduced by the infusion of 1 mM mercaptopropionylglycine (MPG, 2.7+/-0.5 U/ml, p
      < 0.001) or 5 microM vitamin E (11.7+/-0.8 U/ml, p < 0.001), compared to the (PBN
      containing) control (29.7+/-4.3 U/ml). Moreover, functional recovery (left
      ventricular developed pressure, LVDP 91.6 +/-20% of pre-ischemic level, p < 0.05)
      was improved by the hydrophilic radical scavenger MPG, compared to the (PBN
      containing) control (LVDP 50.5+/-15.7% of baseline). PBN alone led to higher
      functional recovery (p < 0.05) and reduced VF (duration of ventricular
      fibrillation; 7.10+/-0.36 min/30 min, p < 0.05), compared to the untreated (PBN
      free) control (LVDP 26.6+/-11.8%; VF 19.42+/-3.64 min/30 min). The Ca antagonist
      verapamil (0.1 microM), MPG, and the lipophilic vitamin E showed cardioprotection
      in the absence of PBN: post-ischemic recovery of LVDP was 25.4+/-6.8% (p < 0.05),
      39.6+/-12.7% (p < 0.05) and 52.4+/-2.6% (p < 0.01), respectively, compared to the
      corresponding untreated control (13.3+/-6.6%). Whereas verapamil and vitamin E
      were able to protect the heart when present alone, they offered no additive
      effect in the presence of PBN. Therefore, PBN can be used to estimate the radical
      scavenger properties of an agent in the heart. However, because of the protective
      properties of PBN itself, the results of simultaneous investigations of the
      effects of other compounds, such as Ca antagonists or lipophilic radical
      scavengers, on heart function may be limited.

PMID- 9774193
TI  - Is stunning prevented by ischemic preconditioning?
AB  - In a model of global ischemia in the isolated perfused rat heart, a 20 min
      ischemic period followed by 30 min of reperfusion induces a decrease in
      isovolumic developed pressure (LVDP) and +dP/dtmax to 61+/-6% and 61+/-7% of
      baseline, respectively. Left ventricular end-diastolic pressure (LVEDP) increases
      to 36+/-4 mmHg at the end of the reperfusion period. No significant necrotic area
      as assessed by triphenyltetrazolium chloride (TTC) was detected at the end of the
      reperfusion period. By an immunohistochemical method using antiactin monoclonal
      antibodies 10.8+/-1.9% of unstained cells were detected in the stunned hearts and
      10.3+/-1.2% in control hearts. Preceding the ischemic episode with a cycle of 5
      min of ischemia followed by 10 min of reperfusion (ischemic preconditioning)
      protected contractile function. LVDP and +dP/dtmax now stabilized at 89+/-5% and
      94+/-5% of baseline respectively. LVEDP was 20+/-2 mmHg at the end of the
      reperfusion period. The protection of contractile dysfunction after 20 min of
      ischemia was achieved also by early reperfusion of low Ca2+-low pH perfusate.
      With this intervention LVDP stabilized at 87+/-5% of baseline. LVEDP was 12+/-2
      mmHg at the end of the reperfusion period. A positive inotropic intervention
      induced by a modified postextrasystolic potentiation protocol at the end of the
      reperfusion period increases LVDP to levels higher than baseline in the stunned
      hearts. However, these values were less than those obtained in control hearts.
      Ischemic preconditioning significantly increased the maximal inotropic response.
      Therefore, ischemic preconditioning diminishes the contractile dysfunction of
      early stunning.

PMID- 9774194
TI  - Physiological and biochemical adrenergic regulation of the stunned myocardium.
AB  - A dual approach was employed to study beta-adrenergic receptor signal
      transduction in post ischemic (stunned) myocardium, examining physiological
      interventions in awake, chronically instrumented pigs and biochemical, cellular
      mechanisms in sarcolemmal preparations from the stunned hearts using the
      contralateral non-ischemic zone as a control. Ten min of coronary artery
      occlusion (CAO) and 30 min coronary artery reperfusion (CAR) resulted in
      depressed posterior wall-thickening (myocardial stunning). Isoproterenol
      increased transmural wall thickening more in stunned myocardium than in non
      ischemic myocardium. In contrast, the responses of wall thickening to forskolin,
      actually decreased during stunning compared with control. NKH 477, a water
      soluble forskolin derivative, that does not activate cardiac nerves, increased
      wall thickening in non-ischemic tissue similarly to the effects on stunned
      myocardium. Increasing cardiac neural tone reflexly with inferior venal caval
      occlusion (IVCO) elicited similar results to forskolin, i.e., stunned myocardium
      responded with less of an increase in wall thickening as compared with non
      ischemic myocardium. Beta-adrenergic receptor density, as determined with 125I
      cyanopindolol binding, was significantly increased in stunned subendocardium and
      subepicardium compared with respective values in non-ischemic myocardium. There
      were no differences in the response of adenylyl cyclase to isoproterenol in
      stunned and non-ischemic myocardium. The enhanced responsiveness of the beta
      adrenergic receptor to isoproterenol stimulation in stunned myocardium
      corresponded to the increase in beta-adrenergic receptor density. The combination
      of enhanced responses to isoproterenol, and decreased responses to forskolin and
      to IVCO and preserved responsiveness to NKH 477, suggest that stunned myocardium
      is characterized by transient sympathetic neural stunning. The enhanced
      sensitivity to beta-adrenergic receptor stimulation has important clinical
      implications, both in terms of therapy of stunned myocardium and detection of
      stunned and/or hibernating myocardium, i.e., low dose dobutamine
      echocardiography.

PMID- 9774195
TI  - Ischemic preconditioning attenuates apoptotic cell death associated with
      ischemia/reperfusion.
AB  - Apoptosis or programmed cell death is a genetically controlled response for cells
      to commit suicide and is associated with DNA fragmentation or laddering. The
      common inducers of apoptosis include oxygen free radicals/oxidative stress and
      Ca2+ which are also implicated in the pathogenesis of myocardial ischemic
      reperfusion injury. To examine whether ischemic reperfusion injury is mediated by
      apoptotic cell death, isolated perfused rat hearts were subjected to 15, 30 or 60
      min of ischemia as well as 15 min of ischemia followed by 30, 60, 90 or 120 min
      of reperfusion. At the end of each experiment, the heart was processed for the
      evaluation of apoptosis and DNA laddering. Apoptosis was studied by visualizing
      the apoptotic cardiomyocytes by direct fluorescence detection of digoxigenin
      labeled genomic DNA using APOPTAG in situ apoptosis detection kit. DNA laddering
      was evaluated by subjecting the DNA obtained from the hearts to 1.8% agarose gel
      electrophoresis and photographed under UV illumination. The results of our study
      revealed apoptotic cells only in the 90 and 120 min reperfused hearts as
      demonstrated by the intense fluorescence of the immunostained digoxigenin-labeled
      genomic DNA when observed under fluorescence microscopy. None of the ischemic
      hearts showed any evidence of apoptosis. These results were corroborated with the
      findings of DNA fragmentation which showed increased ladders of DNA bands in the
      same reperfused hearts representing integer multiples of the internucleosomal DNA
      length (about 180 bp). The presence of apoptotic cells and DNA fragmentation in
      the myocardium were completely abolished by subjecting the myocardium to repeated
      short-term ischemia and reperfusion which also reduced the ischemic reperfusion
      injury as evidenced by better recovery of left ventricular performance in the
      preconditioned myocardium. The results of this study indicate that reperfusion of
      ischemic heart, but not ischemia, induces apoptotic cell death and DNA
      fragmentation which can be inhibited by myocardial adaptation to ischemia.

PMID- 9774196
TI  - The extracellular matrix in hibernating myocardium--a significant factor causing
      structural defects and cardiac dysfunction.
AB  - Recently, we described chronic intracellular degeneration accompanied by fibrosis
      as typical structural features of hibernating myocardium and we concluded that
      cellular degeneration as a sign of the incomplete adaptation to the reduced blood
      flow is characteristic of hibernation. This study has been extended by analyzing
      the composition of the extracellular matrix proteins of the diseased myocardium.
      Areas of hibernating myocardium were identified in 38 patients by angiography,
      multigated radionuclide ventriculography, thallium scintigraphy with reinjection
      and low-dose dobutamine echocardiography. These areas were biopsied at cardiac
      surgery and were studied by electron microscopic and immunofluorescence
      techniques. Electron microscopy showed an enlarged extracellular space containing
      numerous particles of cellular debris, macrophages, fibroblasts, homogeneous
      matrix material and collagen fibrils. The basement membrane of the cardiomyocytes
      was thickened by an augmentation of laminin, fibronectin and collagen VI, but
      these proteins also were present in the matrix itself. Collagen fibrils were
      numerous and macrophages (CD68) and fibroblasts (vimentin) were increased. In
      situ hybridization showed an increase in mRNA for laminin, fibronectin and
      collagen. This observation is consistent with the conclusion that fibrotic scar
      formation was occurring continuously. It is postulated that fibrosis is the
      consequence of myocyte loss due to chronic underperfusion in the hibernating
      tissue. This will further injure myocytes so that a vicious cycle is established
      that leads to progressive loss of structural integrity and functional capacity.
      Since these changes are progressive, revascularization should be performed at the
      earliest time point possible in patients with areas of hibernating myocardium.

PMID- 9774197
TI  - Dedifferentiated cardiomyocytes from chronic hibernating myocardium are ischemia
      tolerant.
AB  - Left ventricular biopsies from 21 patients with clinically diagnosed chronic
      hibernating myocardium (CHM) were examined by light- and electron microscopy. A
      mean of 27% of cardiomyocytes were structurally altered and were characterized as
      hibernating, because of reduced amount of myofibrils and increased glycogen
      content. Electron microscopy of these cells showed reduction of T-tubules and
      numerous small mitochondria, but few changes associated with degeneration, acute
      ischemia or apoptosis. The structural changes found in CHM are reminiscent of
      dedifferentiation rather than degeneration. The expression patterns of some
      structural proteins show resemblance with those in embryonic cardiomyocytes.
      Histochemically, mitochondrial NADH-oxidase and proton translocating ATPase
      activities were absent, whereas cytochrome c activity was present. Intracellular
      calcium distribution indicated normally bound sarcolemmal calcium and absence of
      excess mitochondrial calcium accumulation. Nuclear chromatin ranged from normal
      to dispersed with only a few nuclei that were clumped. These results suggest that
      cardiomyocytes from human CHM hearts are structurally altered, but viable, and
      lack morphologic and cytochemical characteristics suggestive of apoptosis or
      acute ischemia.

PMID- 9774198
TI  - Role of cyclic nucleotide phosphodiesterases in ischemic preconditioning.
AB  - Several signal transduction pathways have been implicated in the mechanism of
      protection induced by ischemic preconditioning (PC). For example, stimulation of
      a variety of G-protein coupled receptors results in stimulation of protein kinase
      C (PKC) which has been suggested to act as common denominator in eliciting
      protection. PC also significantly attenuated cAMP accumulation during sustained
      ischemia, suggesting involvement of an anti-adrenergic mechanism. The aim of this
      study was to evaluate the beta-adrenergic signal transduction pathway (as
      evidenced by changes in tissue cAMP and cAMP- and cGMP-phosphodiesterase) during
      the PC protocol as well as during sustained ischemia. Isolated perfused rat
      hearts were preconditioned by 3 x 5 min global ischemia (PC1,2,3) interspersed by
      5 min reperfusion, followed by 25 min global ischemia. Tissue cAMP- and cGMP-PDE
      activity as well as cAMP and cGMP levels were determined at different time
      intervals during the PC protocol and sustained ischemia. Tissue cAMP increased
      with each PC ischemic event and normalized upon reperfusion, while PDE activity
      showed the opposite, viz a reduction during ischemia and an increase during
      reperfusion. Except for PC1, tissue cGMP showed similar fluctuations. Throughout
      25 min sustained ischemia, cAMP- and cGMP-PDE activities were higher in PC than
      in nonpreconditioned hearts, associated with a significantly lesser accumulation
      in cAMP and higher cGMP levels in the former. Fluctuations in cyclic nucleotides
      during preconditioning were associated with concomitant changes in PDE activity,
      while the attenuated beta-adrenergic response of preconditioned hearts during
      sustained ischemia may partially be due to increased PDE activity.

PMID- 9774199
TI  - Myocardial protection during ischemia and reperfusion.
AB  - The objectives of this article are to: (i) discuss the origins and the nature of
      ischemic injury, (ii) identify factors influencing the evolution of injury, (iii)
      consider various cellular targets for ischemic injury, (iv) assess the overall
      importance of 'reperfusion injury', (v) discuss conceptual approaches to
      cardioprotection and (vi) to identify new ideas and approaches in the realm of
      myocardial protection. In the human heart, myocardial ischemia may take many
      forms, it may exist for periods as short as a few seconds or minutes, it may last
      for hours or it may persist for years. In terms of discussing interventions to
      combat myocardial ischemia, this article will focus on: (i) regional ischemia as
      occurs during evolving myocardial infarction and (ii) whole heart or global
      ischemia as occurs during cardiac surgery and transplantation.

PMID- 9774201
TI  - Hibernating myocardium: its pathophysiology and clinical role.
AB  - Myocardial hibernation, as first defined by Rahimtoola, is a state of chronic
      contractile dysfunction in patients with coronary artery disease which is fully
      reversible upon reperfusion. Clinical conditions consistent with the existence of
      myocardial hibernation include unstable and stable angina, myocardial infarction
      heart failure, and anomalous origin of coronary arteries. The mechanisms of
      hibernation are not known. Morphological alterations have been described in the
      hibernating area of patients, but these information are strongly affected by the
      diagnostic criteria utilized to screen patients. It has been postulated that
      hibernation is an adaptive phenomenon occurring during ischemia. In this context,
      downregulation of contraction is not regarded as a consequence of energetic
      deficit, but as a regulatory event aimed at reducing energy expenditure, thereby
      maintaining integrity and viability. Thus, hibernation might bear a relationship
      to the phenomenon of low-flow perfusion-contraction matching, or repetitive
      stunning or preconditioning. Clear-cut evidence for the mechanism of hibernation
      in the clinical setting seems likely to remain elusive, because of the nature of
      the studies needed to document it. Current experimental evidence supports the
      view that hibernation, stunning, preconditioning, or their coexistence can be
      responsible for regional myocardial contractile dysfunction which is reversible
      upon reperfusion. These are all adaptive and protective phenomena independent of
      their terminology and strict definitions and do not always apply to the extremely
      complex situation of myocardial ischemia in man.

PMID- 9774200
TI  - Features of short-term myocardial hibernation.
AB  - When severe ischemia, such as that resulting from a sudden and complete coronary
      artery occlusion, is prolonged for more than 20-40 min, myocardial infarction
      develops, and there is irreversible loss of contractile function. When myocardial
      ischemia is less severe but nevertheless prolonged, the myocardium is
      dysfunctional but can remain viable. In such ischemic and dysfunctional
      myocardium, contractile function is reduced in proportion to the reduction in
      regional myocardial blood flow; i.e. a state of 'perfusion-contraction matching'
      exists. The metabolic status of such myocardium improves over the first few
      hours, as myocardial lactate production is attenuated and creatine phosphate,
      after an initial reduction, returns towards control values. Ischemic myocardium,
      characterized by perfusion-contraction matching, metabolic recovery and lack of
      necrosis, has been termed 'short-term hibernating myocardium'. Short-term
      hibernating myocardium can respond to inotropic stimulation with increased
      contractile function, although at the expense of renewed worsening of the
      metabolic status. This occurrence of increased regional contractile function at
      the expense of metabolic recovery during inotropic stimulation can be used to
      identify short-term hibernating myocardium. When inotropic stimulation is
      prolonged, short-term hibernation is impaired and myocardial infarction develops.
      The mechanisms responsible for the development of short-term myocardial
      hibernation remain unclear at present. Significant involvement of adenosine and
      activation of ATP-dependent potassium channels have been excluded. The role of
      triggering events and acidosis is controversial. Short-term hibernating
      myocardium is, however, characterized by reduced calcium responsiveness.

PMID- 9774202
TI  - Non-ischemic myocardial preconditioning.
AB  - The reduction of infarct size produced by brief ischemic episodes prior to a
      sustained occlusion of a coronary artery, called ischemic preconditioning, is a
      well known phenomenon that occurs in several species, but its mechanism is still
      under investigation. Recent reports support the idea that this protection can
      also be obtained by non-ischemic maneuvers like distention of the left ventricle
      and metabolic stimulation of myocardial cells. The features of non-ischemic
      preconditioning (temporal limitation, second window, tolerance development,
      remote preconditioning and efficiency of the protection), as opposed to those of
      ischemic preconditioning, are still to be determined. Neither is it known if non
      ischemic preconditioning occurs in humans. From a physiological point of view the
      protective effect of an increase in metabolic rate of the heart means a constant
      feed-back mechanism in the myocardial cell that counteracts the presumptive
      damage consequent to the increase in metabolism. Therefore, in the presence of a
      sudden coronary occlusion the metabolic rate of the heart immediately before the
      occlusion would have a dual role of increasing the degree of ischemia and of
      protecting against it.

PMID- 9774203
TI  - Fat metabolism during exercise: a review--part III: effects of nutritional
      interventions.
AB  - By changes in nutrition it is possible to manipulate fat oxidation. It is often
      theorized that increasing fat oxidation may reduce glycogen breakdown and thus
      enhance performance. Therefore, the effects of acute, short-term and long-term
      fat feeding have been subjects of investigation for many years. Ingestion of long
      chain triacylglycerols (LCT) during exercise may reduce the gastric emptying rate
      and LCT will appear in the plasma only slowly. Medium-chain triacylglycerols
      (MCT) do not have these disadvantages and they are rapidly oxidized. However, the
      contribution of MCT to energy expenditure is only small because they can only be
      ingested in small amounts without causing gastrointestinal distress. So at
      present, fat supplementation in the hours preceding to or during exercise (either
      long chain or medium chain triacylglycerols) cannot be recommended. High-fat
      diets and fasting have been suggested to increase fatty acid availability and
      spare muscle glycogen resulting in improved performance. Both fasting and short
      term high-fat diets will decrease muscle glycogen content and reduce fatigue
      resistance. Chronic high-fat diets may provoke adaptive responses preventing the
      decremental effects on exercise performance. However, at present, there is little
      evidence to support this hypothesis. Also from a health perspective, caution
      should be exercised when recommending high-fat diets to athletes.

PMID- 9774204
TI  - Effect of "living high-training low" on the cardiac functions at sea level.
AB  - Living high-training low (LHTL), living at high altitude and training at sea
      level, is reported to be beneficial in enhancing physical performance. Effect of
      LHTL on cardiac function which is one of major determinants in performance,
      however, was not examined. To address this issue, 21 well-trained triathletes
      divided into control (n = 10, living and training at sea level) and LHTL group
      (living at 1980 m altitude > or = 12 hrs/day and training at sea level) were
      Doppler echocardiographically examined before and at the end of the two-week
      program. Heart rate and blood pressure did not change in both groups. At end of
      the training, left ventricular endsystolic diameter of LHTL group was smaller
      than that of controls (32 vs 34 mm, P < 0.05). Shortening fraction and ejection
      fraction in LHTL group increased by 9% and 17 %, respectively, P < 0.05.
      Preejection period/ejection time was more greatly reduced in LHTL group (P <
      0.05). Stroke volume and cardiac output in LHTL increased. Diastolic function was
      not significantly affected by LHTL. These results suggest that LHTL produced an
      improvement of systolic function underlined by incremented left ventricular
      contractility, which might be associated with increased beta-adrenergic receptor
      or an improved myocardial energy utilization.

PMID- 9774205
TI  - Cardiac responses to exercise in child distance runners.
AB  - Cardiovascular responses to exercise in trained endurance child athletes have
      been largely unexplored. Doppler echocardiography was utilized to compare cardiac
      variables during progressive upright cycle exercise to exhaustion in trained male
      prepubertal distance runners (n = 8) and untrained control boys (n = 14).
      Athletes demonstrated a greater maximal stroke index and cardiac index. Stroke
      volume rose progressively with increasing workloads in the runners but remained
      stable beyond low intensities in the non-athletes. No significant differences in
      stroke volume were observed between the two groups at rest. This contrasts with
      the greater resting stroke volumes typically seen in adult endurance athletes
      compared to non-athletes. Likewise, values for maximal stroke index were less in
      the child runners than those typically seen in trained adults. This study
      demonstrated that the stroke volume response to exercise differs in boy runners
      compared to non-athletes. The findings also suggest quantitative differences in
      such responses between prepubertal and young adult athletes.

PMID- 9774206
TI  - Vascular control of nutrient delivery by flow redistribution within muscle:
      implications for exercise and post-exercise muscle metabolism.
AB  - There is evidence for non-nutritive flow routes within, or associated with,
      skeletal muscle. Large capillary-like structures are possible candidates. The
      proportion of flow distributed between nutritive and non-nutritive routes appears
      to be tightly regulated and can control muscle metabolism and contraction by
      regulating delivery and product removal. The portion of flow that is carried by
      the non-nutritive routes at rest affords a flow reserve for amplifying nutrient
      delivery as muscle begins to work and may determine post-exercise metabolism.
      Inappropriate signals, however, may diminish nutritive flow to the detriment of
      muscle performance and post-exercise recovery. New technologies should allow the
      identification of the non-nutritive routes.

PMID- 9774207
TI  - Mechanical output and electromyographic parameters in males and females during
      fatiguing knee-extensions.
AB  - The purpose of this study was to elucidate if the m. quadriceps femoris was fully
      activated during the first contractions of a series of repetitive maximal
      contractions and if there was any difference in the development of fatigue
      between sexes. To do this sixteen untrained subjects performed two series of
      contractions in an isokinetic dynamometer: one series of single maximum
      contractions and one series of repetitive maximum contractions. The EMG activity
      of m. vastus lateralis, m. vastus medialis and m. rectus femoris was recorded.
      The subjects were unable to perform maximum effort during the first repetitions
      of each trial, which might influence the results of fatigue studies, if these
      contractions are chosen as reference. We also found in contrast to other studies
      a decrease in RMS between the reference contraction and the fatigue level. We
      have not been able to display any difference between males and females during
      fatigue either in relative mechanical output nor in electromyographic parameters
      or experience in fatigue during isokinetic knee-extensions.

PMID- 9774208
TI  - Effects of an interval training programme of the upper limbs on a wheelchair
      ergometer in able-bodied subjects.
AB  - The effects of a 6 weeks interval training with a wheelchair ergometer on the
      power and endurance of the upper limbs (UL) were studied in ten young able-bodied
      males. All subjects performed a maximal progressive test (10 W/2 min) on a
      wheelchair ergometer to measure the ventilation (VE), respiratory exchanges (VO2,
      VCO2) and oxygen pulse (O2p) at the maximal tolerated power (MTP) and ventilatory
      threshold (VT). Endurance capacity was measured with the tailored 45 min Square
      Wave Endurance Exercise Test (SWEET) from MTP and VT. Arm and forearm perimeters,
      diameters and skinfold thickness were also measured. The subjects were divided
      into a control group (CG n = 5) and a training group (TG n = 5; 3 SWEET
      sessions/week/6-week) with matched physical characteristics. Training the UL
      resulted in significant increases of parameters at MTP (power + 63%, peak VO2 +
      33%, O2 pulse + 25%) and at VT (power + 125%, VO2 + 48%, O2 pulse + 33%). The UL
      diameter and perimeter significantly increased, and the skinfold thickness
      decreased. None of these variables showed a significant change in the CG. We
      conclude that this training improves specific force and endurance of the UL, by
      acting centrally as reflected by oxygen pulse increase, as well as peripherally
      as shown by morphologic changes.

PMID- 9774209
TI  - Carbohydrate ingestion immediately before exercise does not improve 20 km time
      trial performance in well trained cyclists.
AB  - This study examined the effects of carbohydrate ingestion on 20 km cycle time
      trial (TT) performance in 14 well-trained cyclists (11 males, 3 females; peak
      oxygen uptake [VO2peak] 4.52 +/- 0.60 l/min; values are mean +/- SD). All
      subjects performed two experimental trials on their own bicycles mounted on an
      air-braked ergometry system (Kingcycle). Subjects were instructed to maintain the
      same training and dietary regimens before trials, which were conducted in a
      random order, 3-7 days apart, and at the same time of day for each subject. On
      the day of a trial, subjects reported to the laboratory and ingested an 8 ml/kg
      body mass bolus of either a 6.8 g/100 ml commercial carbohydrate-electrolyte
      (CHO) beverage (39 +/- 4 g of CHO), or a coloured, flavoured placebo. Ten min
      after finishing the drink, subjects commenced a 5 min warm-up at 150 W, before
      commencing the 20 km TT. The average power output (312 +/- 40 vs 311 +/- 38 W)
      and heart-rate (171 +/- 6 vs 171 +/- 5 beats/min for CHO and placebo,
      respectively) during the two rides did not differ between treatments.
      Accordingly, the performance times for the two TT's were the same (27:41 +/- 1:39
      min:sec, for both CHO and placebo). We conclude that the ingestion of
      approximately 40 g of carbohydrate does not improve maximal cycling performance
      lasting approximately 30 min, and that carbohydrate availability, in the form of
      circulating blood glucose, does not limit high-intensity exercise of this
      duration.

PMID- 9774210
TI  - Glycogen depletion patterns in trained rats adapted to a high-fat or high
      carbohydrate diet.
AB  - Male Sprague-Dawley rats (n = 48, > 200 g) were progressively treadmill trained
      over 5 wk where they were running 60 min/d, 5 d/wk. One-half of the group
      consumed a high-fat diet (HF, 78.7% of energy), while one-half consumed a high
      carbohydrate diet (HC, 68.7% of energy). On the day of the experiment, 6 rats per
      diet were run at 29 m/min, 8% grade for 0, 10, 20, or 60 min. Immediately post
      exercise rats were anesthetized, and soleus (S), red vastus lateralis (RV), and
      white vastus lateralis (WV) muscles were removed. There were no significant
      differences between diets for S glycogen pre-, during, or post-exercise. RV
      glycogen (micromol x g(-1) wet wt) was lower (p < 0.05) at rest for the HF (27.5
      +/- 3.9, Mean +/- SEM) vs the HC (37.6 +/- 3.5), but similar to HC at 60 min
      (11.0 +/- 1.9, HF; 8.6 +/- 1.3, HC). RV glycogen use rates (nmol x g(-1) x min(
      1)) were lower for the HF (985 +/- 295, 356 +/- 61) than the HC (1593 +/- 144,
      1055 +/- 272) for 0-10 and 11-20 min, respectively. Resting WV glycogen was lower
      for the HF (25.3 +/- 1.6) vs the HC (40.7 +/- 5.8), while post exercise values
      were similar (17.0 +/- 4.4, HF; 15.7 +/- 2.0, HC). WV glycogen use was negligible
      from 0-10 and 11-20 min in the HF compared to the HC (280 +/- 169 and 1601 +/-
      177 nmol x g(-1) x min(-1), respectively). These data indicate that muscle
      glycogen is spared during the early stages of prolonged exercise in HF adapted
      rats and that the sparing occurs according to expected muscle recruitment
      patterns.

PMID- 9774211
TI  - Intestinal IgA- and IgM-producing cells are not decreased in marathon runners.
AB  - Alterations in duodenal immunoglobulin (Ig-)producing cells after excessive
      physical stress (marathon running) were studied by immunohistochemistry in 11
      well-trained male adults, both shortly after running (race time, approximately
      3.00 h) and later on after a "resting period" of 8-12 weeks with normal training
      (7-20 h/week). The ratios of IgA-, IgM- and IgG-producing cells were similar in
      the two biopsy specimens and virtually identical to those in eight normal
      duodenal controls (medians 77.6% IgA, 18.6% IgM, and 2.5% IgG). However, in the
      first sample the total number of positive cells per intestinal length unit was
      increased in five for IgA and in seven for IgM, while it was decreased in eight
      for IgG compared with the second biopsy. Also, the IgA cell number tended to be
      slightly increased immediately after the race (median 128 cells/unit) compared
      with that in normal controls (median 111 cells/unit); the same tendency was found
      for all Ig classes considered together. This apparent change was not explained by
      a thickening of the mucosa. Our study showed that marathon runners seem to
      maintain or even enhance their intestinal IgA and IgM-production, in contrast to
      the IgA decrease reported for other compartments such as salivary secretions and
      peripheral blood. The tendency to slightly increased intestinal IgA and IgM
      immunocyte populations in some runners might reflect a stress-induced hormonal
      influence on the homing of primed B cells to the mucosa, or perhaps an immune
      response to elevated influx of stimulatory luminal antigens.

PMID- 9774212
TI  - Differential white cell count after two bouts of downhill running.
AB  - The purpose of this study was to compare blood markers associated with
      eccentrically biased exercise and muscle damage, after two bouts of downhill
      running. Nine active, untrained males performed 2 x 45 min bouts of downhill
      running (-0.16 radians), at a speed that would elicit 70% of each subjects
      VO2max, on a level grade; runs were spaced 14d apart (RUN1, RUN2). Blood samples
      were obtained before, after, and every hour for 12 h after exercise, as well as
      every 24 h for 5 d, to assess numbers of circulating neutrophils, monocytes, and
      lymphocytes, serum cortisol, creatine kinase (CK); subjective sensations of
      delayed onset muscle soreness (DOMS) were monitored. To control for diurnal
      variation, two weeks prior to the RUN1, subjects had blood draws performed at the
      same time as would occur after exercise, but did no exercise (CONTROL). During
      the 5 d after exercise, DOMS and CK were significantly greater (p < 0.05) after
      RUN1 compared to RUN2 and CONTROL. During the 12 h after RUN1 and RUN2,
      neutrophils showed similar responses compared to CONTROL. However, neutrophils
      were significantly elevated at 96 h after RUN1 and 24 h after RUN2. Monocytes
      were significantly elevated during 5-11 h after RUN1 and RUN2, compared to
      CONTROL. Cortisol showed a similar significant diurnal decrease for all three
      conditions during the 12 h following exercise. The significantly lower levels of
      CK and DOMS seen after RUN2, compared with the initial run is consistent with the
      literature. The similar changes in neutrophils and monocytes during the 12 h
      following RUN1 and RUN2, followed by disparate responses over the subsequent 5 d,
      requires further investigation.

PMID- 9774213
TI  - Specific interaction of 5-HT-moduline with human 5-HT1b as well as 5-HT1d
      receptors expressed in transfected cultured cells.
AB  - 5-HT1B receptors are the predominant auto- and heteroreceptors located on
      serotonergic and non-serotonergic terminals where they regulate the neuronal
      release of neurotransmitters. 5-HT-moduline (Leu-Ser-Ala-Leu) has been shown to
      specifically interact with a very high apparent affinity and in a non-competitive
      manner with 5-HT1B receptors (Massot et al. 1996; Rousselle et al. 1996). Using
      transfected cells expressing either 5-HT1B or 5-HT1D receptors, it was shown that
      5-HT-moduline prevents the binding of [3H]5-HT to 5-HT1B as well as to 5-HT1D
      receptors with similar biochemical characteristics: the IC50 of the peptide was
      1.2x10(-12) M for 5-HT1B and 9x10(-13) M for 5-HT1D receptors. The observed
      effect corresponds to a marked decrease of the maximal binding for [3H]5-HT on 5
      HT1B (-51.2 +/- 1%) as well as 5-HT1D binding (-47.2 +/- 7.7% of the control
      binding) whereas the affinity of 5-HT is increased by a factor close to 3. No
      effect is observed using the "scrambled" peptide (Ala-Leu-Leu-Ser). Parallel
      assays using transfected cells expressing 5-HT1A or 5-ht6 receptors did not show
      any significant change induced by the peptide under similar assay conditions. The
      interaction of the peptide was also studied on the functional activity related to
      the stimulation of the receptors as measured by the increase in [35S]GTPgammaS
      binding reflecting the coupling of the receptor to the G-protein. 5-HT-moduline
      yields an antagonistic effect on the 5-HT induced coupling with a corresponding
      IC50 = 1.2 +/- 0.7x10(-12) M for 5-HT1B and 9.8 +/- 4.0x10(-12) M for 5-HT1D
      receptors, respectively. The present results demonstrate that 5-HT-moduline
      interacts with 5-HT1D as well as 5-HT1B receptors and possesses a non-competitive
      antagonistic activity, likely corresponding to its role of endogenous allosteric
      modulator, specific for both 5-HT1B and 5-HT1D receptors.

PMID- 9774214
TI  - Evidence for CCK(B) receptors in the guinea-pig kidney: localization and
      characterization by [125I]gastrin binding studies and by RT-PCR.
AB  - Two types of receptors for gastrin and cholecystokinin (CCK) have been identified
      in the gastrointestinal tract and in the central nervous system: CCK(A) and
      CCK(B) receptors. Here we report evidence for the expression of CCK(B) receptors
      in the guinea-pig kidney. Specific binding sites for [125I]gastrin were detected
      in sections of the guinea-pig kidney: Binding was saturable, pH-, temperature-
      and time-dependent, and specific for gastrin-related peptides. The potencies for
      inhibition of binding of [125I]gastrin were CCK-8 > gastrin 17-I > CCK(B)
      receptor antagonist L-365,260 > des(SO3)CCK-8 > CCK(A) receptor antagonist L
      364,718. Autoradiography demonstrated specific [125I]gastrin binding to medullary
      collecting ducts and to a much lesser extent to glomeruli, but not over other
      structures. CCK(B) receptor cDNA fragments were amplified by RT-PCR from total
      kidney, isolated tubuli and from tissues known to express CCK(B) receptors such
      as stomach and brain. The kidney might therefore be a previously unidentified
      site of action for gastrin and cholecystokinin-related peptides.

PMID- 9774216
TI  - Functional characterization of alpha1-adrenoceptor subtypes in the rabbit spleen.
AB  - Phenylephrine and (+/-)N-[5-(4,5-dihydro-1-H-imidazol-2yl)-2-hydroxy-5,6,7,8-tetr
      ahydronaphthalen-1-yl] methanesulphonamide hydrobromide (A 61603) evoked
      concentration-dependent contractions of the rabbit spleen. These contractions
      were antagonized by prazosin (10(-8)-10(-7) M) with pA2 values of 8.34+/-0.11 and
      8.15+/-0.10 against phenylephrine and A 61603, respectively. In both cases, the
      slopes of the Schild plots were not significantly (P>0.05) different from 1.0,
      indicating competitive antagonism. The effects of subtype-selective antagonists
      WB 4101 [2-(2-6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane hydrochloride]
      and 5-methylurapidil on agonist-induced contractions were also examined. WB 4101
      competitively antagonized agonist-induced contractions; pA2 values were 8.13+/
      0.10 and 8.10+/-0.03 against phenylephrine and A 61603, respectively.
      Corresponding values for 5-methylurapidil were 8.28+/-0.17 and 7.93+/-0.02
      against phenylephrine and A 61603, respectively. Tamsulosin and Rec 15/2739 [(8-3
      [4-(2-methoxyphenyl)-1-piperazinyl]-propylcarbamoyl)-3-methy l-4-oxo-2-phenyl-4H
      1-benzopyran dihydrochloride] also antagonized phenylephrine- and A 61603-induced
      contractions with pA2 values of 9.38+/-0.13 and 9.18+/-0.06 (tamsulosin) and
      8.41+/-0.12 and 8.34+/-0.11 (Rec 15/2739) against phenylephrine and A 61603,
      respectively. HV 723 (alpha-ethyl-3,4,5-trimethoxy-alpha-(3-((2-(2
      methoxyphenoxyethyl) -amino)-propyl)benzene-aceto-nitrile) fumarate)
      competitively antagonized phenylephrine-induced contractions with a pA2 value of
      8.57+/-0.06. Chloroethylclonidine (CEC; 10(-4) M) shifted phenylephrine and A
      61603 concentration-response curves to the right, reducing their potencies
      approximately two- to threefold, while the maximum response was reduced by 8% in
      both cases. It was therefore concluded that contractions of the rabbit spleen
      induced by alpha1-adrenergic agonists were mediated predominantly by a relatively
      CEC-insensitive alpha1-adrenoceptor subtype, possibly the alpha1L-subtype.

PMID- 9774215
TI  - Tachykinin NK2 receptors in the hamster urinary bladder: in vitro and in vivo
      characterization.
AB  - We have characterized the contractile responses produced by stimulation of the
      tachykinin NK2 receptor in the hamster urinary bladder in vitro and in vivo. In
      isolated bladder strips, neurokinin A (NKA, pD2 7.40, Emax 71% of the response to
      80 mM KCl) and the synthetic tachykinin NK2 receptor selective agonist
      [betaAla8]NKA(4-10) (pD2 7.48, Emax 77% of the response to KCl) both induced a
      concentration-dependent contraction, whereas the tachykinin NK1 and NK3 receptor
      selective agonists, [Sar9]substance P sulfone and senktide, respectively,
      produced a negligible contractile effect. The bicyclic peptide antagonists MEN
      11420 and MEN 10627 behaved as competitive antagonists of the response to
      [betaAla8]NKA(4-10) with apparent pK(B) values of 9.3 and 9.7, respectively.
      Comparable apparent pK(B) values were estimated against NKA (pK(B) 9.2 and 9.4
      for MEN 11420 and MEN 10627, respectively). Under isovolumetric recording of the
      intravesical pressure, the nicotinic receptor agonist DMPP (0.6 micromol/kg i.v.)
      produced a phasic contraction of the hamster bladder in vivo that was abolished
      by hexamethonium (110 micromol/kg i.v.) or by surgical ablation of pelvic
      ganglia. In vivo [betaAla8]NKA(4-10) (10 nmol/kg i.v.) induced a tonic-type
      sustained bladder contraction with superimposed high frequency and small
      amplitude (<12 mmHg) phasic contractions and, in about 70% of cases examined, a
      few high amplitude (>20 mmHg) phasic contractions. Hexamethonium abolished the
      high amplitude phasic contractions, indicating their reflex origin. In animals
      subjected to the ablation of pelvic ganglia, the urinary bladder response to
      [betaAla8]NKA(4-10) was comparable to that observed after administration of
      hexamethonium. Moreover, hexamethonium did not affect the contractile responses
      to [betaAla8]NKA(4-10) in ganglionectomized animals. MEN 10627 and MEN 11420
      produced a dose-dependent and long-lasting inhibition of the contractile response
      to [betaAla8]NKA(4-10): the least effective doses of the two antagonists were 30
      and 3 nmol/kg i.v. for MEN 10627 and MEN 11420, respectively. An almost complete
      and long-lasting inhibition of the response to the agonist was produced at doses
      of 10 and 100 nmol/kg i.v. of MEN 11420 and MEN 10627. In urethane-anaesthetized
      hamsters the non-stop intravesical infusion of saline (50 microl/min) produced
      repetitive micturition cycles which were abolished by hexamethonium (110
      micromol/kg i.v.) or by surgical removal of the pelvic ganglia. MEN 11420 (100
      nmol/kg) had no significant effect on the volume-evoked micturition reflex in
      anaesthetized hamsters. In conclusion, the hamster urinary bladder is a suitable
      preparation for studying the action of tachykinin NK2 receptor antagonists in
      vivo: in this species, the stimulation of tachykinin NK2 receptors induces
      bladder contractions. Blockade of tachykinin NK2 receptors does not appreciably
      modify the volume-evoked micturition reflex in this species.

PMID- 9774217
TI  - Atherogenic lipoproteins inhibit catecholamine secretion in cultured bovine
      adrenal medullary cells.
AB  - The effects of lipoproteins on ion channel-mediated catecholamine secretion were
      investigated in cultured bovine adrenal medullary cells. Low density lipoprotein
      (LDL: 20-80 mg/dl) and lipoprotein(a) [Lp(a); 10-80 mg/dl] inhibited
      catecholamine secretion induced by carbachol, an activator of nicotinic
      acetylcholine receptor-ion channels. LDL and Lp(a) suppressed carbachol-induced
      22Na+ influx as well as 45Ca2+ influx in a concentration-dependent manner similar
      to that of catecholamine secretion. The inhibition of catecholamine secretion by
      Lp(a) was not overcome by increasing the concentration of carbachol. On the other
      hand, high density lipoprotein (HDL; < 150 mg/dl) had no effect on 22Na+ influx,
      45Ca2+ influx, and catecholamine secretion. Like LDL and Lp(a), a synthetic
      peptide homologous to human plasma apolipoprotein B (apoB), apoB fragment(3358
      3372)-amide (3-60 microM), attenuated 22Na+ influx, 45Ca2+ influx, and
      catecholamine secretion caused by carbachol. The apoB fragment also suppressed
      22Na+ influx induced by veratridine (an activator of voltage-dependent Na+
      channels) and 45Ca2+ influx induced by 56 mM K+ (an indirect activator of voltage
      dependent Ca2+ channels). These findings suggest that atherogenic lipoproteins
      such as LDL and Lp(a) suppress catecholamine secretion by interfering with Na+
      influx through nicotinic acetylcholine receptor-ion channels, in which apoB, a
      structural component common to both LDL and Lp(a), plays an important role. The
      inhibition by atherogenic lipoproteins of catecholamine secretion may influence
      the progression of atherosclerosis induced by these lipoproteins.

PMID- 9774218
TI  - In vivo control of 5-hydroxytryptamine release by terminal autoreceptors in rat
      brain areas differentially innervated by the dorsal and median raphe nuclei.
AB  - Selective serotonin reuptake inhibitors (SSRIs) reduce the 5-HT release in vivo.
      This effect is due to the activation of somatodendritic 5-HT1A receptors and it
      displays a regional pattern comparable to that of selective 5-HT1A agonists,
      i.e., preferentially in forebrain areas innervated by the dorsal raphe nucleus
      (DRN). However, despite a comparatively lower 5-HT1A-mediated inhibition of 5-HT
      release and a greater density of serotonergic uptake sites in hippocampus, the
      net elevation produced by the systemic administration of SSRIs is similar in
      various forebrain areas, regardless of the origin of serotonergic fibres. As
      terminal autoreceptors may also limit the SSRI-induced elevations of 5-HT in the
      extracellular brain space, we reasoned that a differential control of 5-HT
      release by terminal autoreceptors in DRN- and median raphe-innervated areas might
      be accountable. To examine this possibility, we have conducted a regional
      microdialysis study in the DRN, MRN and four forebrain regions preferentially
      innervated either by the DRN (frontal cortex, striatum) or the median raphe
      nucleus (MRN; dorsal and ventral hippocampus) using freely moving rats. Dialysis
      probes were perfused with 1 microM of the SSRI citalopram to augment the
      endogenous tone on terminal 5-HT autoreceptors. The non-selective 5-HT1
      antagonist methiothepin (10 and 100 microM, dissolved in the dialysis fluid)
      increased extracellular 5-HT in frontal cortex and dorsal hippocampus in a
      concentration-dependent manner. The 5-HT(1B/1D) antagonist GR 127935 was
      ineffective at 10 microM and tended to reduce 5-HT in dorsal hippocampus at 100
      microM. The local infusion of 100 microM methiothepin significantly elevated the
      extracellular 5-HT concentration to 142-173% of baseline (mean values of 260 min
      post-administration) in the DRN, MRN, frontal cortex, striatum and hippocampus
      (dorsal and ventral). Comparable elevations were noted in the four forebrain
      regions examined. As observed in frontal cortex and dorsal hippocampus, the
      perfusion of 10 microM GR 127935 did not elevate 5-HT in DRN. MRN, striatum or
      ventral hippocampus. Because the stimulated 5-HT release in the DRN has been
      suggested to be under control of 5-HT(1B/1D) receptors, we examined the possible
      contribution of these receptor subtypes to the effects of methiothepin in the
      DRN. The perfusion of sumatriptan (0.01-10 microM) or GR 127935 (0.01-10 microM)
      did not significantly modify the 5-HT concentration in dialysates from the DRN.
      Thus, the present data suggest that the comparable effects of SSRIs in DRN- and
      MRN-innervated forebrain regions are not explained by a preferential attenuation
      of 5-HT release by terminal 5-HT1B autoreceptors in hippocampus, an area with a
      low inhibitory influence of somatodendritic 5-HT1A receptors. Methiothepin
      sensitive autoreceptors (possibly 5-HT1B) appear to play an important role not
      only in the projection areas but also with respect to the control of 5-HT release
      in the DRN and MRN. In addition, our findings indicate that GR 127935 is not an
      effective antagonist of the actions of 5-HT at rat terminal autoreceptors.

PMID- 9774219
TI  - In vitro studies on the mechanism by which (+)-norfenfluramine induces serotonin
      and dopamine release from the vesicular storage pool.
AB  - (+)-Norfenfluramine is the main metabolite of the serotoninergic anorectic agent
      (+)-fenfluramine. Both compounds inhibit 5-HT reuptake and stimulate its release,
      although they induce release from different pools, with (+)-norfenfluramine
      acting primarily on the cytoplasmic pool. Moreover, (+)-norfenfluramine was more
      potent than the parent drug in inducing dopamine release. In order to investigate
      whether (+)-norfenfluramine induces a Ca2+-dependent vesicular release, like some
      amphetamine derivatives, in the present study we preloaded synaptosomes with the
      [3H]neurotransmitter ([3H]5-HT or [3H]dopamine), superfused (washed) them for 47
      min in the absence of pargyline and then exposed them to the releasing stimulus.
      With this protocol, the cytoplasmic pool should be absent and the
      [3H]neurotransmitter should mainly be stored in synaptic vesicles, where (+)
      norfenfluramine should act to induce release. This was confirmed by a significant
      decrease of (+)-norfenfluramine-induced [3H]5-HT and [3H]dopamine release after
      reserpine pretreatment. The dose-response curves of (+)-norfenfluramine-induced
      [3H]5-HT release were superimposable in hippocampus and hypothalamus, and also
      superimposable on the curve for (+)-fenfluramine-induced [3H]5-HT release; the
      dopamine releasing potency of (+)-norfenfluramine in the striatum was more than
      ten times lower. The [3H]5-HT release induced by (+)-norfenfluramine was partly
      (about 50%) but significantly Ca2+-dependent, and it was also markedly (68%)
      inhibited by Cd2+, a non-specific blocker of voltage-dependent Ca2+ channels,
      suggesting that the Ca2+-dependent release is mediated by entry of Ca2+ into the
      synaptosomes through these channels. The [3H]dopamine release induced by 5 microM
      (+)-norfenfluramine was completely Ca2+-independent whereas at higher
      concentrations (10 and 20 microM) it was only slightly (20%) Ca2+-dependent. We
      have no clear explanation why (+)-norfenfluramine has these different effects on
      serotoninergic and dopaminergic synaptosomes.

PMID- 9774220
TI  - Ketamine interacts with the noradrenaline transporter at a site partly
      overlapping the desipramine binding site.
AB  - Effects of the intravenous anaesthetic ketamine on the desipramine-sensitive
      noradrenaline transporter (NAT) were examined in cultured bovine adrenal
      medullary cells and in transfected Xenopus laevis oocytes expressing the bovine
      NAT (bNAT). Incubation (1-3 h) of adrenal medullary cells with ketamine (10-300
      microM) caused an increase in appearance of catecholamines in culture medium.
      Ketamine (10-1000 microM) inhibited desipramine-sensitive uptake of
      [3H]noradrenaline (NA) (IC50=97 microM). Saturation analysis showed that ketamine
      reduced Vmax of [3H]NA uptake without changing Km, indicating a non-competitive
      inhibition. Other inhibitors of NAT, namely cocaine and desipramine, showed a
      competitive inhibition of [3H]NA uptake while a derivative of ketamine,
      phencyclidine, showed a mixed type of inhibition. Ketamine (10-1000 microM) also
      inhibited the specific binding of [3H]desipramine to plasma membranes isolated
      from bovine adrenal medulla. Scatchard analysis of [3H]desipramine binding
      revealed that ketamine increased Kd without altering Bmax, indicating a
      competitive inhibition. In transfected Xenopus oocytes expressing the bNAT,
      ketamine attenuated [3H]NA uptake with a kinetic characteristic similar to that
      of cultured adrenal medullary cells. These findings are compatible with the idea
      that ketamine non-competitively inhibits the transport of NA by interacting with
      a site which partly overlaps the desipramine binding site on the NAT.

PMID- 9774221
TI  - Effects of NNC 711, a GABA uptake inhibitor, on pentylenetetrazol-induced
      seizures in developing and adult rats.
AB  - The anticonvulsant action of NNC 711 [(1-(2-((diphenylmethylene) amino) oxy)
      ethyl)-1,2,4,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride], an inhibitor
      of the GABA transporter GAT-1, was studied in a model of pentylenetetrazol
      induced motor seizures in rats 7, 12, 18, 25, and 90 days old. NNC 711 at doses
      of 0.25-20 mg/kg i.p. exhibited two effects in rat pups: a suppression of minimal
      clonic seizures in age groups in which this type of seizure could be reliably
      elicited (i.e. in rats aged 18 and 25 days); and a specific suppression or
      restriction of the tonic phase of generalized tonic-clonic seizures (GTCS)
      expressed in 18- and especially 12-day-old rats. Effects of NNC 711 on GTCS in 7-
      and 25-day-old rats were irregular. Adult (i.e. 90-day-old) animals exhibited
      abolition of generalized tonic-clonic seizures; minimal clonic seizures were
      suppressed only after substantially higher doses. The abolition of minimal
      seizures by doses too low to influence generalized tonic-clonic seizures as
      observed in rat pups is unique among antiepileptic drugs. In addition, an EEG
      study in rat pups demonstrated dissociation of EEG signs and motor seizures in
      some animals.

PMID- 9774222
TI  - Central administration of dopamine D3 receptor antisense to rat: effects on
      locomotion, dopamine release and [3H]spiperone binding.
AB  - A 15-mer, all-phosphorothioate-modified antisense oligodeoxynucleotide (ASO)
      targeted against rat dopamine D3 receptor mRNA (4 microM, 5 days) significantly
      reduced (28%) the amount of binding sites labelled with [3H]spiperone in
      monolayer cultured Chinese hamster ovary (CHO) cells transfected with the
      complementary desoxyribonucleic acid (cDNA) for the rat D3 receptor. In contrast,
      D3-ASO treatment did not reduce the amount of bound [3H]spiperone in CHO cells
      transfected with D2 receptor cDNA. Intracerebroventricular infusion of D3-ASO
      (osmotic minipump, 10 microg/microl/h, 7 days) influenced dopamine receptor
      density in the limbic forebrain such that the upper part of the
      dopamine/[3H]spiperone displacement curve--tentatively representing the D3
      receptor--was altered significantly. Spontaneous locomotor activity of non
      habituated rats was increased significantly in D3-ASO-treated animals; in
      addition, in vivo microdialysis revealed a moderate increase in dopamine release
      in the nucleus accumbens in these animals. In all experiments, an
      oligodeoxynucleotide comprising the same nucleotides as the antisense sequence,
      but in random order, was used as control. It is concluded that the antisense
      strategy is useful for investigating the functional role of dopamine D3 receptors
      and that the dopamine D3 receptor is involved in rat locomotor behaviour.

PMID- 9774223
TI  - Effects of nicotine on hydroxyl free radical formation in vitro and on MPTP
      induced neurotoxicity in vivo.
AB  - Parkinson's disease (PD) is one of the most frequent disorders of the basal
      ganglia. From epidemiological studies there is a controversial discussion on the
      question whether tobacco smoking is correlated with a decreased incidence of PD.
      The present study aimed to elucidate the role of nicotine and its potential
      neuroprotective effects in a rodent model of PD. These effects may be related to
      an altered hydroxyl radical formation; this possibility was studied in vitro.
      Nicotine and alpha-phenyl-N-tert-butyl nitrone (PBN) were examined in a cell-free
      in vitro Fenton system (Fe3+/EDTA + H2O2) for their radical scavenging properties
      using the salicylate trapping method. Salicylic acid (0.5 mM) was incubated in
      the presence and absence of nicotine or PBN and the main products of the reaction
      of hydroxyl radicals with salicylic acid, namely 2,3- and 2,5-dihydroxybenzoic
      acid, were immediately determined using HPLC in combination with electrochemical
      detection. Nicotine and PBN were both able to significantly reduce hydroxyl
      radical levels at concentrations of 1, 2.5 and 5 mM. Interestingly, at 5 mM
      nicotine was able to reduce hydroxyl radical levels significantly more than the
      radical scavenger PBN (5 mM). To investigate the in vivo effects of nicotine,
      male C57BL/6 mice were used in the MPTP mouse model of PD. Nicotine (0.1 or 0.4
      mg/kg s.c.) was administered twice daily for a period of 14 days. On day 8 a
      single injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg
      s.c.) was given as well as an enhanced protocol of nicotine treatment (0.1 or 0.4
      mg/kg s.c., 30 min before MPTP and 30, 90, 210, 330, 450, 570 min after MPTP) for
      a total of seven injections of nicotine. High dosage nicotine treatment
      significantly increased the MPTP-induced loss of body weight and resulted in a
      significantly decreased striatal dopamine content and an increased dopamine
      turnover in comparison with the MPTP-treated controls at day 15. However, the
      lower dosage of nicotine did not significantly alleviate the MPTP-induced
      effects, although some parameters showed a slight tendency in this direction.
      These results demonstrate that in vitro nicotine has radical scavenging
      properties which might suggest neuroprotective effects. In vivo experiments with
      nicotine, however, showed that a low dosage of nicotine did not alleviate the
      MPTP-induced dopamine depletion, but a large dosage even enhanced it.

PMID- 9774224
TI  - Diminution of contractile response by kappa-opioid receptor agonists in isolated
      rat ventricular cardiomyocytes is mediated via a pertussis toxin-sensitive G
      protein.
AB  - Opioids directly decrease the contractile response of isolated ventricular
      cardiomyocytes to electrical stimulation. To investigate whether these effects
      are mediated via GTP-binding G(i/o) proteins we examined the influence of
      pertussis toxin on the effects of the kappa-opioid receptor agonist trans-(+/-)
      3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benz eneacetamide (U
      50,488) methanesulphonate and on the as yet undescribed effects of the opioid
      peptide dynorphin A (1-8) on contraction. In isolated, electrically driven, rat
      ventricular cardiomyocytes both agents concentration dependently reduced cell
      shortening within 15 min, decreasing the contractile response by 79+/-4% (n=5)
      and 62+/-2% (n=6) of control values at maximal effective concentrations of 10
      microM (U-50,488) and 1 microM [dynorphin A (1-8)], respectively. Pertussis toxin
      pre-treatment (200 ng/ml; 4.5-5 h) completely abolished the effects of U-50,488
      and dynorphin A (1-8) on the contractile response, indicating that these effects
      are mediated via G(i/o) proteins. In addition, the non-selective opioid receptor
      antagonist (-)-naloxone and the kappa-opioid receptor antagonist nor
      binaltorphimine antagonized the effects of U-50,488 and dynorphin A (1-8) on the
      contractile response. Furthermore, the mu- and delta-opioid receptor agonist (D
      Ala2, D-Leu5)-enkephalin (DADLE) had no effects on contraction. These results
      indicate that the decrease in cell shortening is due to stimulation of kappa
      opioid receptors. The direct effect of kappa-opioid receptor agonists on the
      contractile response thus represents an additional mechanism for decreasing
      cardiac contractility, besides the M-cholinoceptor- or adenosine receptor
      mediated pathway. It is conceivable that increased release of endogenous
      dynorphins from the heart during hypoxia may protect the heart in a similar
      manner to adenosine.

PMID- 9774225
TI  - Intratubular application of sodium azide inhibits loop of Henle reabsorption and
      tubuloglomerular feedback response in anesthetized rats.
AB  - Sodium azide (NaN3, AZ) is a potent inhibitor and uncoupler of oxidative
      phosphorylation as well as a nitrovasodilator after being converted to nitric
      oxide (NO). We studied the effect of intratubular application of AZ on loop of
      Henle reabsorption and tubuloglomerular feedback (TGF) employing renal
      micropuncture experiments in nephrons with superficial glomeruli of anesthetized
      Munich-Wistar-Fromter rats. During perfusion of Henle's loop downstream from an
      obstructing wax block, AZ (3x10(-5) mol/l and 3x10(-4) mol/l) concentration
      dependently increased early distal tubular flow rate and sodium and potassium ion
      concentration (V(ED), [Na+]ED, [K+]ED). In comparison, application of furosemide
      (10(-4) mol/l), the action of which is restricted to the water-impermeable thick
      ascending limb of Henle's loop (TALH) and the macula densa, similarly increased
      [Na+]ED and [K+]ED, but did not affect V(ED). The effect of AZ on loop of Henle
      reabsorption appeared to be predominantly localized upstream to the TALH since
      (1) AZ significantly inhibited net fluid reabsorption (the latter being
      completely abolished at 3x10(-4) mol/l), (2) the effect of AZ on [Na+]ED and
      [K+]ED could be mimicked by perfusing the Henle's loop at a flow rate that caused
      a comparable increase in V(ED) (reflecting a comparable load to TALH), and (3)
      the effects of AZ and furosemide were additive. In spite of the increase in
      [Na+]ED and [K+]ED, intratubular application of AZ caused a concentration
      dependent inhibition of TGF response, the latter being assessed as the fall in
      early proximal tubular stop flow pressure during perfusion of Henle's loop at
      increasing flow rate. Like AZ and furosemide, the NO donor sodium nitroprusside
      (10(-4) mol/l) blunted the TGF response, but in contrast to furosemide or AZ, it
      caused a minor decrease in V(ED), without changing [Na+]ED or [K+]ED. The
      inhibitory effect of AZ on TGF was abolished by the NO scavenger carboxy PTIO. In
      summary, AZ inhibits both reabsorption in the water-permeable segment of Henle's
      loop and the TGF response. The effect on reabsorption may be linked to metabolic
      inhibition rather than NO release, whereas the blunted TGF response appears to
      involve conversion to NO.

PMID- 9774226
TI  - A K+ single channel and whole-cell clamp study on the effects of levocromakalim
      in guinea pig portal vein cells.
AB  - Single channel cell-attached patch and whole-cell clamp experiments on the mode
      of action of the K+ channel opener (KCO), levcromakalim, were performed in guinea
      pig isolated portal vein cells. At +20 mV (135/23 mM K+ in bath/pipette), 10
      microM levcromakalim activated K+ channels with a chord conductance of 23.2 pS
      (K(KCO)), which were sensitive to the blocker of ATP-dependent K+ channels
      (K(ATP)), glibenclamide. Voltage steps from -80 mV to +20 mV activated 4
      aminopyridine-sensitive K+ channels of 6.5 pS with properties of delayed
      rectifier K+ channels (Kv). In patches which upon a previous voltage step had
      revealed the existence of Kv, levcromakalim reduced the open-probability of Kv,
      but it did not concomitantly activate K(KCO). During the course of the
      experiments, but unrelated to the presence of levcromakalim, large conductance K+
      channels (BK(Ca)) appeared which could be inhibited by iberiotoxin, a selective
      blocker of BK(Ca), and by the membrane-permeant calcium buffer, BAPTA/AM, but not
      by glibenclamide. Whole-cell current-voltage (i-V) relations were established in
      response to voltage ramps from +50 mV to -100 mV; on subtraction of control i-V
      curves from i-V curves obtained in the presence of 10 microM levcromakalim, the
      KCO-induced K+ current remained which was proportional to voltage. This is not
      compatible with the upward-bent curvature predicted by the GHK current equation
      for purely resistive channels at high [K+]i versus low [K+]o. In conclusion, in
      the guinea pig portal vein cells, no evidence could be established for the
      hypotheses that KCOs may act via conversion of Kv to K(ATP) (Beech and Bolton
      1989; Edwards et al. 1993) or by activation of BK(Ca) (Balwierczak et al. 1995).
      In these cells, mild inward rectification of the levcromakalim-induced current
      was observed which underlines their relationship to K(ATP) in other tissues.

PMID- 9774227
TI  - Stimulation of natural killer activity in peripheral blood lymphocytes of healthy
      donors and melanoma patients in vitro: synergism between interleukin (IL)-12 and
      IL-15 or IL-12 and IL-2.
AB  - Interleukin-2 (IL-2) and IL-12 modify the functional status of T- and natural
      killer (NK) cells by regulating proliferation, cytolytic activity, cytokine
      induction, and T-cell subset differentiation. These effects are exploited in
      immunotherapy of cancer patients with IL-2 or IL-12, which, however, is limited
      by potentially life-threatening side effects. IL-15 shares many of the biological
      activities of IL-2 and may therefore represent a therapeutic alternative. Here we
      have compared the ability of these interleukins to stimulate NK activity in
      peripheral blood lymphocytes (PBLs) isolated from healthy donors (n = 12) as well
      as from patients (n = 12) suffering from metastatic disease (melanoma). Target
      (K562) cell lysis was assessed by determining the release of 51Cr and lactate
      dehydrogenase (LDH) which gave equivalent results. The NK-resistant DAUDI cell
      line served as control target. Unstimulated NK activity was significantly lower
      in PBLs purified from melanoma patients. However, cytolytic activity was readily
      stimulated by preincubation of PBLs (18 h) with cytokines such that the maximum
      target cell lysis was comparable to that seen in PBL of healthy donors.
      Similarly, the potency of IL-2 (EC50 = 20.2+/-1.3 and 22.0+/-1.3 u/ml in healthy
      donors and patients, respectively), IL-12 (EC50 = 11.0+/-1.1 and 4.3+/-1.6 u/ml)
      and IL-15 (EC50 = 0.3+/-0.1 and 0.2+/-0.1 u/ml) was comparable. Importantly, if
      the preincubation was carried out with cytokine concentrations in the EC50 range,
      the effects of two cytokines (tested in all combinations) were additive. A
      synergism was evident in PBLs obtained both from healthy donors and melanoma
      patients if concentration-response curves for IL-12 were determined in the
      presence of increasing concentrations of IL-2 (enhanced efficacy) or IL-15
      (enhanced efficacy and potency). Our observations suggest possible alternatives
      to the monotherapy with IL-2 (or IL-12) in cancer treatment. Provided that the
      present findings can be extrapolated to the situation in vivo, the combined
      administration of IL-12 and IL-15 may be as efficacious as the immunotherapy with
      IL-2; this approach ought to allow for a marked reduction in cytokine dose and
      thereby improve the therapeutic index.

PMID- 9774228
TI  - No evidence for PKC activation in stimulation of insulin secretion by
      phentolamine.
AB  - The possible role of protein kinase C (PKC) activation in the course of insulin
      secretion induced by the imidazoline phentolamine was investigated by measuring
      the insulin secretion of perifused mouse islets and of insulin-secreting HIT
      cells and by measuring the PKC activity of HIT cells. When normal mouse islets
      were perifused with the imidazoline phentolamine (32 microM) or the sulfonylurea
      glibenclamide (1 microM), neither phentolamine nor glibenclamide could produce a
      stimulation of secretion which was stronger than that elicited by a strong
      depolarization. Under the same conditions, tetradecanoylphorbolacetate (TPA, 50
      nM), a known activator of PKC activity in pancreatic islets, markedly enhanced
      the secretion induced by K+ depolarization. Phentolamine also stimulated insulin
      secretion of superfused HIT cells. When PKC activity in HIT cells was down
      regulated to 15% of the initial value by overnight exposure to TPA (50 nM), the
      stimulatory effect of TPA on secretion was virtually abolished, while
      phentolamine was still able to elicit a monophasic secretion. TPA (50 nM) induced
      the typical redistribution of PKC activity in HIT cells: within 2 min, the share
      of membrane-bound PKC activity rose from 26% to 87% of the total PKC activity,
      which remained unchanged. In contrast, phentolamine (32 microM) had no effect on
      PKC distribution, did not down-regulate PKC and had no effect on PKC activity
      once it was down-regulated by TPA. Thus, the recent suggestion that the
      insulinotropic effect of imidazolines involves an activation of PKC could not be
      verified for phentolamine.

PMID- 9774229
TI  - A concise methodology for the stereoselective synthesis of O-glycosylated amino
      acid building blocks: complete 1H NMR assignments and their application in solid
      phase glycopeptide synthesis.
AB  - A facile strategy for the stereoselective synthesis of suitably protected O
      glycosylated amino acid building blocks, namely, Nalpha-Fmoc-Ser-[Ac4-beta-D-Gal
      (1-3)-Ac2-alpha or beta-D-GalN3]-OPfp and Nalpha-Fmoc-Thr-[Ac4-beta-D-Gal-(1-3)
      Ac2-alpha or beta-D-GalN3]-OPfp is described. What is new and novel in this
      report is that Koenigs-Knorr type glycosylation of an aglycon serine/threonine
      derivative (i.e. Nalpha-Fmoc-Ser-OPfp or Nalpha-Fmoc-Thr-OPfp) with protected
      beta-D-Gal(1-3)-D-GalN3 synthon mediated by silver salts resulted in only alpha-
      and/or beta-isomers in excellent yields under two different reaction conditions.
      The subtle differences in stereoselectivity were demonstrated clearly when
      glycosylation was carried out using only AgClO4 at -40 degrees C which afforded a
      isomer in a quantitative yield (alpha:beta = 5:1). On the other hand, the beta
      isomer was formed exclusively when the reaction was performed in the presence of
      Ag2CO3/AgClO4 at room temperature. A complete assignment of 1H resonances to
      individual sugar ring protons and the characteristic anomeric alpha-1 H and beta
      1 H in Ac4Galbeta(1-3)Ac2GalN3 alpha and/or beta linked to Ser/Thr building
      blocks was accomplished unequivocally by two-dimensional double-quantum filtered
      correlated spectroscopy and nuclear Overhauser enhancement and exchange
      spectroscopy NMR experiments. An unambiguous structural characterization and
      documentation of chemical shifts, including the coupling constants for all the
      protons of the aforementioned alpha- and beta-isomers of the O-glycosylated amino
      acid building blocks carrying protected beta-D-Gal(1-3)-D-GalN3, could serve as a
      template in elucidating the three-dimensional structure of glycoproteins. The
      synthetic utility of the building blocks and versatility of the strategy was
      exemplified in the construction of human salivary mucin (MUC7)-derived, O-linked
      glycopeptides with varied degrees of glycosylation by solid-phase Fmoc chemistry.
      Fmoc/tert-butyl-based protecting groups were used for the peptidic moieties in
      conjunction with acetyl sugar protection. The transformation of the 2-azido group
      into the acetamido derivative was carried out with thioacetic acid on the polymer
      bound glycopeptides before the cleavage step. After cleaving the glycopeptide
      from the resin, the acetyl groups used for sugar OH-protection were removed with
      sodium methoxide in methanol. Finally, the glycopeptides were purified by
      reversed-phase high-performance liquid chromatography and their integrity was
      confirmed by proton NMR as well as by mass spectral analysis. Secondary structure
      analysis by circular dichroism of both the glycosylated and nonglycosylated
      peptides revealed that carbohydrates did not exert any profound structural effect
      on the peptide backbone conformation.

PMID- 9774230
TI  - Synthesis of lipopeptides using hydrazone chemical ligation.
AB  - In this paper we report that a hydrazinopeptide synthesized using solid-phase N
      electrophilic amination with N-Boc-3-(4-cyanophenyl)oxaziridine reacted with a
      lipophilic peptide aldehyde to give the corresponding hydrazone plus an
      unexpected 1,3,4-oxadiazolidinopeptide containing two peptide aldehyde units.
      This methodology allows the synthesis of large lipopeptides.

PMID- 9774231
TI  - Interaction of gonadotropin-releasing hormone and its agonist analogs with Ca2+
      in a nonpolar milieu. Correlation with biopotencies.
AB  - Extracellular Ca2+ is necessary for the action of gonadotropin-releasing hormone
      (GnRH). Assuming that this partly because of the interaction of the hormone with
      the relatively abundant extracellular Ca2+ in the low dielectric milieu of the
      bilayer plasma membrane, we studied the interaction of GnRH and five of its
      agonist analogs with Ca2+ under membrane-mimetic conditions. The peptides used,
      in increasing order of their reported gonadotropin-releasing activities, were:
      des-amide GnRH (or GnRH-OH); [Ala6]GnRH; [D-Ala6]GnRH; des-Gly10[D-Ala6,Pro9
      NHEt]GnRH and, des-Gly10[D-Trp6,Pro9-NHEt]GnRH. Changes in the far-UV CD and
      fluorescence spectra of these peptides in trifluoroethanol were used to monitor
      conformational changes and obtain the Ca2+-binding isotherms. The data show that
      GnRH and its active analogs contain two Ca2+ binding sites, whereas the inactive
      analogs have only one. The extent of Ca2+ binding by the agonist peptides
      paralleled their biological potency ranking. The superactive analog des-Gly10[D
      Trp6,Pro9-NHEt]GnRH exhibited the ability to transport Ca2+ ions across large
      unilamellar vesicles of dimyristoylphosphatidylcholine. Our study shows that
      significant differences among the GnRH and its analog peptides, suggestive of
      differences in their conformations, are manifested only in the presence of Ca2+.
      This observation would provide a basis for understanding GnRH action in terms of
      the hormone's interaction with Ca2+ in the lipid milieu.

PMID- 9774232
TI  - Amino acids with aryl-keto function in their side chains.
AB  - Amino acids with aryl-keto function in their side-chains were obtained in
      excellent yields in the reaction of omega-carboxyamino acids with liquid HF in
      the presence of aromatic compounds susceptible to electrophilic substitution,
      such as anisole, 2-methoxybiphenyl, butyl phenyl ether or 1,3-dimethoxybenzene.
      The new amino acids were converted smoothly into N-tert-butyloxycarbonyl or N
      fluorenylmethoxycarbonyl derivatives and then incorporated into peptides by
      conventional coupling methods. During the coupling step, no formation of cyclic
      Schiff bases was observed for aryl-keto amino acids derived from DL-alpha
      aminopimelic acid and from L-alpha-aminosuberic acid. In the crude products,
      truncated peptides terminated at the keto amino acids were not detected by liquid
      chromatography-mass spectrometry.

PMID- 9774233
TI  - The asymmetric synthesis of arginine mimetics: derivatives of (S)-2-, 3- and 4
      amidinophenylalanine suitable for incorporation into enzyme inhibitors and/or
      peptides.
AB  - The specific inhibition of trypsin-like serine proteases has become an important
      therapeutic target. These proteases have been implicated in several physiological
      and pathophysiological processes, including blood coagulation, digestion, and
      inflammation. Proteases of this class cleave polypeptide chains C-terminal to a
      basic residue (arginine or lysine). It has been shown that selectivity for a
      particular serine protease can be conferred based upon the structural moiety
      incorporated in the P1 position. In this regard, the three isomers (ortho, meta,
      and para) of amidinophenylalanine represent modified arginine residues and are
      important synthetic targets. Herein, a convenient asymmetric synthesis of (S)
      Nalpha-(tert-butyloxycarbonyl)-2-, (S)-Nalpha-(tert-butyloxycarbonyl)-3-, and (S)
      Nalpha-(tert-butyloxycarbonyl)-4-amidinophenyl-alanine N,O-dimethylamides
      (Weinreb amides) will be described. These derivatives represent key synthetic
      intermediates for the synthesis of enzyme inhibitors because the amidine can be
      readily orthogonally protected, while the Weinreb amide is easily converted to a
      variety of electrophilic carbonyls via reduction to the corresponding aldehyde or
      by reaction with various lithiated heterocycles. Likewise, the Weinreb amide can
      be reduced to the aldehyde and subsequently oxidized to the corresponding
      carboxylate, which is suitable for solid- or solution-phase peptide synthetic
      strategies.

PMID- 9774234
TI  - Crystal structure of Boc-LAla-deltaPhe-deltaPhe-deltaPhe-deltaPhe-NHMe: a left
      handed helical peptide.
AB  - Alpha,beta-dehydrophenylalanine residues constrain the peptide backbone to beta
      bend conformation. A pentapeptide containing four consecutive (deltaPhe) residues
      has been synthesised and crystallised. The peptide Boc-LAla-deltaPhe-deltaPhe
      deltaPhe-deltaPhe+ ++-NHMe (C45H46N6O7, MW = 782.86) was crystallised from an
      acetonitrile/methanol mixture. The crystal belongs to the orthorhombic space
      group P2(1)2(1)2(1) with a = 19.455(6), b = 20.912(9), c = 11.455(4) A and Z = 4.
      The X-ray (MoKalpha, lambda = 0.7107 A) intensity data were collected using the
      Rigaku-AFC7 diffractrometer. The crystal structure was determined by direct
      methods and refined using the least-squares technique, R = 8.41% for 1827
      reflections with absolute value of Fo > 4sigma(absolute value of Fo). The
      molecule contains the largest stretch of consecutive dehydrophenylalanine
      residues whose crystal structure has been determined so far. The peptide adopts
      left-handed 3(10)-helical conformation despite the presence of LAla at the N
      terminus. The mean phi, psi values, averaged across the last four residues are
      56.8 degrees and 17.5 degrees, respectively. There are four 4-->1 intramolecular
      hydrogen bonds, characteristic of the 310-helix. In the crystal each molecule
      interacts with four crystallographically symmetric molecules with one hydrogen
      bond each.

PMID- 9774235
TI  - Synthesis, solution conformation and interleukin-6-related activities of
      interleukin-6 peptides.
AB  - Interleukin-6 (IL-6) is a member of the cytokine superfamily characterised by a
      wide variety of biological activities on various cell types. IL-6 exerts
      pleiotropic activities on hematopoiesis in the immune response and it is the main
      regulator of acute-phase protein synthesis in liver cells. According to structure
      function studies, residues of helix A located at the N-terminal part and/or helix
      D of the C-terminal part of the protein are involved in the induction of acute
      phase responses. Two groups of synthetic peptides corresponding to the 18-46 N
      terminal and the 168-185 C-terminal regions of the IL-6 were prepared by solid
      phase synthesis to identify structural requirements for induction of fibrinogen
      or complement factor B synthesis. These peptides were characterised by amino acid
      analysis, analytical reversed-phase high-performance liquid chromatography, fast
      atom bombardment mass spectrometry, and circular dichroism (CD) spectroscopy. CD
      results showed that under appropriate conditions both 18-46 and 168-185 related
      peptides are able to adopt markedly ordered conformation. We demonstrated that
      even octapeptides from the N-terminal part and truncated derivatives of the C
      terminal region preserved some tendency to display the CD curve of periodic
      conformation. The ability of the peptides to induce de novo synthesis of acute
      phase proteins was evaluated by measuring fibrinogen and complement factor B
      levels in the supernatants of human HepG2 cells. These results showed that
      residues 21-34 are critical for eliciting fibrinogen synthesis in the presence or
      absence of IL-6. In contrast, the full-length 168-185 peptide is required for the
      induction of complement factor B response.

PMID- 9774236
TI  - One peptide, two topologies: structure and interconversion dynamics of human
      uroguanylin isomers.
AB  - The peptide hormone uroguanylin stimulates chloride secretion via activation of
      intestinal guanylyl cyclase C (GC-C). It is characterized by two disulfide bonds
      in a 1-3/2-4 pattern that causes the existence of two topological stereoisomers
      of which only one induces intracellular cGMP elevation. To obtain an unambiguous
      structure-function relationship of the isomers, we determined the solution
      structure of the separated uroguanylin isoforms using NMR spectroscopy. Both
      isomers adopt well-defined structures that correspond to those of the isomers of
      the related peptide guanylin. Furthermore, the structure of the GC-C-activating
      uroguanylin isomer A closely resembles the structure of the agonistic Escherichia
      coli heat-stable enterotoxin. Compared with guanylin isomers, the conformational
      interconversion of uroguanylin isomers is retarded significantly. As judged from
      chromatography and NMR spectroscopy, both uroguanylin isoforms are stable at low
      temperatures, but are subject to a slow pH-dependent mutual isomerization at 37
      degrees C with an equilibrium isomer ratio of approximately 1:1. The
      conformational exchange is most likely under the sterical control of the carboxy
      terminal leucine. These results imply that GC-C is activated by ligands
      exhibiting the molecular framework corresponding to the structure of uroguanylin
      isomer A.

PMID- 9774237
TI  - Conformational studies of a potent Leu11,D-Trp12-containing lactam-bridged
      parathyroid hormone-related protein-derived antagonist.
AB  - Human parathyroid hormone-related protein (PTHrP) is expressed in various tissues
      where it acts as an endocrine/paracrine factor involved in cellular growth,
      differentiation and development of fetal skeleton. As for parathyroid hormone
      (PTH), which is the hormone responsible for regulation of extracellular calcium
      homeostasis, the N-terminal 1-34 fragment can reproduce the full spectrum of
      calciotropic activities inherent in full-length PTH. Truncation of six amino acid
      residues from the N-terminus of both hormone sequences generates 7-34 fragments
      which act as weak antagonists. Although PTH(7-34) is a pure antagonist, PTHrP(7
      34) acts as partial agonist against the receptor shared by both hormones, the
      PTH/PTHrP receptor. In the current study, we analyzed the conformation of
      [Leu11,D-Trp12, Lys26,Asp30]PTHrP(7-34)NH2 (hybrid-lactam) in a 1:1 mixture of
      H2O/TFE-d3 at pH approximately equal to 4 by circular dichroism, nuclear magnetic
      resonance and distance geometry calculations. This weak antagonist (Kb = 650 nM)
      combines two modifications: Leu11,D-Trp12 (Kb = 5.1 nM), reported to eliminate
      partial agonism and enhance potency, and Lys26-Asp30 lactamization (Kb = 31 nM),
      aimed to stabilize the helical structure of the principal binding domain
      attributed to residues 25-34. The helical content in 30% trifluoroethanol is 88%,
      i.e., higher than the corresponding linear analog, and comprises the D-Trp12
      Thr33 segment. This hybrid lactam contains a rigid helical segment spanning the
      14-18 sequence followed by a hinge motif around Arg19-20, but the sequence 14-18
      forms a stable helix. In all potent lactam-containing, PTHrP-derived agonists and
      antagonists studied so far, the dominant structural motif consists of two helical
      domains at the two ends of the sequence and of two hinge regions centered around
      Gly12-Lys13 and Arg19. The weakly active agonists and antagonists do not exhibit
      the "hinge" around position 19. These findings suggest that the presence and
      location of discrete hinge regions that connect the N- and C-terminal helices are
      essential for generating the bioactive conformation of ligands for the PTH/PTHrP
      receptor.

PMID- 9774238
TI  - Riluzole delayed appearance of parkinsonian motor abnormalities in a chronic MPTP
      monkey model.
AB  - Preliminary studies have shown that riluzole, a Na+ channel blocker with
      antiglutamatergic activity, has neuroprotective efficacy in several models of
      acute dopaminergic neurodegeneration. A chronic 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) monkey model which comes closer to the slow evolution
      of Parkinson's disease has recently been developed in order to allow dynamic
      studies. The present results show that riluzole delayed the appearance of
      parkinsonian motor abnormalities in this dynamic model, using from 10.2 +/- 1.6
      daily injections for the MPTP-treated monkeys (n = 4) to 16.5 +/- 2.0 daily
      injections for the MPTP + riluzole-treated monkeys (n = 4). These results
      strongly suggest that riluzole may be beneficial to slow down the rate of
      progression of Parkinson's disease.

PMID- 9774239
TI  - Reserpine does not induce orofacial dyskinesia in spontaneously hypertensive
      rats.
AB  - The nigrostriatal dopaminergic system seems to be involved in both reserpine
      induced orofacial dyskinesia in normal rats and in the pathogenesis of
      hypertension in spontaneously hypertensive rats. In the present study, repeated
      reserpine administration (1.0 mg/kg, s.c., every other day, for 3 days) increased
      tongue protrusion and vacuous chewing frequencies as well as the duration of
      facial twitching in Wistar normotensive but not in spontaneously hypertensive
      rats. These results suggest that genetic hypertension and drug-induced orofacial
      movements may be inversely modulated by similar mechanisms in the nigrostriatal
      dopaminergic system.

PMID- 9774240
TI  - Unexpected antipsychotic-like activity with the muscarinic receptor ligand
      (5R,6R)6-(3-propylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo[3.2.1]octane .
AB  - (5R,6R)6-(3-propylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo[3 .2.1]octane (PTAC)
      is a potent muscarinic receptor ligand with high affinity for central muscarinic
      receptors and no or substantially less affinity for a large number of other
      receptors or binding sites including dopamine receptors. The ligand exhibits
      partial agonist effects at muscarinic M2 and M4 receptors and antagonist effects
      at muscarinic M1, M3 and M5 receptors. PTAC inhibited conditioned avoidance
      responding, dopamine receptor agonist-induced behavior and D-amphetamine-induced
      FOS protein M5 expression in the nucleus accumbens without inducing catalepsy,
      tremor or salivation at pharmacologically relevant doses. The effect of PTAC on
      conditioned avoidance responding and dopamine receptor agonist-induced behavior
      was antagonized by the acetylcholine receptor antagonist scopolamine. The
      compound selectively inhibited dopamine cell firing (acute administration) as
      well as the number of spontaneously active dopamine cells (chronic
      administration) in the limbic ventral tegmental area (A10) relative to the non
      limbic substantia nigra, pars compacta (A9). The results demonstrate that PTAC
      exhibits functional dopamine receptor antagonism despite its lack of affinity for
      the dopamine receptors and indicate that muscarinic receptor partial agonists may
      be an important new approach in the medical treatment of schizophrenia.

PMID- 9774241
TI  - Neurochemical effects of the enantiomers of mirtazapine in normal rats.
AB  - The present study was designed to examine the neurochemical effects of (+/-)
      mirtazapine (10 mg kg(-1) i.p.) and its enantiomers in rats. Male Sprague-Dawley
      rats received either (+)-mirtazapine, (-)-mirtazapine, (+/-)-mirtazapine or
      vehicle, by intraperitoneal injection for two weeks. Maximum change in
      temperature from baseline, following a single dose of the 5-HT1A receptor agonist
      8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.15 mg kg(-1) s.c.), was
      used to assess the function of the 5-HT1A receptors. Chronic drug treatment
      potentiated this response, with (+/-)-mirtazapine > (-)-mirtazapine > (+)
      mirtazapine. Receptor changes were also observed with a slight decrease in beta1
      adrenoceptor density, although this failed to reach significance. A significant
      decrease in beta1-adrenoceptor affinity was observed following (-)-mirtazapine
      treatment. All drugs tested significantly reduced the density of the 5-HT2
      receptors. Results of the present study suggest that in so far as alterations in
      these receptor populations are important for the therapeutic action of
      antidepressants, neither of the enantiomers appear to be more active than the
      racemic mixture.

PMID- 9774242
TI  - No change of brain extracellular catecholamine levels after acute catechol-O
      methyltransferase inhibition: a microdialysis study in anaesthetized rats.
AB  - Catechol-O-methyltransferase inhibitors have been newly introduced as adjunct
      drugs to the levodopa/dopa decarboxylase inhibitor therapy in Parkinson's
      disease. When given alone, catechol-O-methyltransferase inhibitors seem to affect
      behaviour. We wanted to determine whether the concentrations of free amine would
      be increased by catechol-O-methyltransferase inhibition with tolcapone and
      underpin the positive behavioural effects. To this end, dopamine and
      noradrenaline levels were analyzed in the microdialysis perfusion fluid collected
      from several brain regions in chloral hydrate anaesthetized rats. We also
      analyzed the turnover rate of catecholamines in the brain after single doses of
      tolcapone and entacapone using the alpha-methyl-p-tyrosine method. On their own,
      tolcapone (at 10 or 30 mg/kg) did not elevate dopamine or noradrenaline levels in
      any brain region studied although the formation of catechol-O-methyltransferase
      dependent metabolites was strongly reduced. Neither tolcapone nor entacapone (at
      30 mg/kg) affected the turnover rate of catecholamines. It seems that catechol-O
      methyltransferase inhibitors do not alter behaviour by elevating extracellular
      levels of free catecholamines levels but other explanations are needed.

PMID- 9774243
TI  - Antinociception produced by the peptidase inhibitor, RB 101, in rats with adrenal
      medullary transplant into the spinal cord.
AB  - This study was undertaken to investigate the effects induced by the systemic
      administration of RB 101 [N-[(R,S)-2-benzyl-3[(S)(2-amino-4-methylthio)butyl
      dithio]-1-oxoprpyl]-L-phenylalanine benzyl ester], a mixed inhibitor of the
      enkephalin catabolism able to cross the blood-brain barrier, in antinociception
      produced by adrenal medullary tissue transplanted in the rat spinal subarachnoid
      space. For this purpose, the antinociceptive responses induced by intravenous
      (i.v.) administration of RB 101 were evaluated in the tail-flick in rats
      transplanted 28 and 56 days before the test. Systemic administration of RB 101
      induced antinociceptive effects in sham-operated rats, as previously reported. RB
      101 also enhanced significantly the antinociception produced by the
      autotransplant 28 and 56 days after surgery. The antinociceptive responses of RB
      101 in both sham-operated and autotransplanted rats were blocked by naloxone, but
      were not modified by the noradrenergic antagonist, phentolamine, suggesting a
      selective involvement of opioid mechanisms. The present results indicate that the
      inhibitors of enkephalin catabolism enhance the antinociception induced by
      adrenal medullary transplants.

PMID- 9774244
TI  - Presynaptic inhibitory action of the group II metabotropic glutamate receptor
      agonists, LY354740 and DCG-IV.
AB  - Electrophysiological studies were carried out on the presynaptic inhibitory
      action of the group II metabotropic glutamate (mGlu) receptor agonists (+)-2
      aminobicyclo[3.1.0]hexane-2-6-dicarboxylic acid (LY354740) and (2S,1'R,2'R,3'R)-2
      (2',3'-dicarboxycyclopropyl)glycine (DCG-IV) in three paths of the rat
      hippocampus, the medial and lateral perforant path to the dentate gyrus, and the
      Schaffer collateral/commissural path to CA1. LY354740 caused a dose-dependent
      reversible inhibition of the field excitatory postsynaptic potential (EPSP) in
      the medial and lateral perforant paths, with an EC50 of 115 +/- 16 nM and 230 +/-
      58 nM, respectively. Maximal inhibition by LY354740 was much greater in the
      medial path (about 80%) than in the lateral path (about 50%). No inhibition was
      observed in CA1. A presynaptic inhibition was confirmed by LY354740 inducing dose
      dependent changes in paired-pulse depression/facilitation. DCG-IV had a similar
      action to LY354740, but with a lower potency.

PMID- 9774245
TI  - The role of group II metabotropic glutamate receptors in hippocampal CA1 long
      term potentiation in vitro.
AB  - The role of group II metabotropic glutamate receptors (mGlu receptors) in
      mechanisms of long-term potentiation was investigated by analysis of excitatory
      postsynaptic field potentials of the CA1 region in rat hippocampal slices. The
      application of the group II agonists (2S,1'S,2'S)-2-(carboxycyclopropyl) glycine
      (L-CCG-I) and (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl) glycine (DCG IV)
      resulted in a dose-dependent reduction of long term potentiation in the
      concentration range 3-50 microM. In contrast to the effects of group II agonists
      on long-term potentiation, the group II antagonists (RS)-alpha-methyl-3-carboxy-4
      hydroxy-phenylglycine (M3C4HPG) and (RS)-alpha-methylserine-O-phosphate
      monophenyl ester (MSOPPE) elicited a dose-dependent enhancement of long-term
      potentiation (50-100 microM or 20-50 microM, respectively). We conclude that
      group II mGlu receptors are not essential for the induction of long-term
      potentiation; however, they may be involved in feedback mechanisms in long-term
      potentiation.

PMID- 9774246
TI  - The 5-HT1A receptor antagonist p-MPPI blocks 5-HT1A autoreceptors and increases
      dorsal raphe unit activity in awake cats.
AB  - The effects of the putative 5-HT1A receptor antagonist 4-iodo-N-[2-[4
      (methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-benzam ide (p-MPPI) were
      examined on the activity of serotonergic dorsal raphe nucleus neurons in freely
      moving cats. Systemic administration of p-MPPI produced a dose-dependent increase
      in firing rate. This stimulatory effect of p-MPPI was evident during wakefulness
      (when serotonergic neurons display a relatively high level of activity), but not
      during sleep (when serotonergic neurons display little or no spontaneous
      activity). p-MPPI also blocked the ability of the 5-HT1A receptor agonist 8
      hydroxy-(2-di-n-propylamino)tetralin (8-OH-DPAT) to inhibit serotonergic neuronal
      activity. This antagonism was evident both as a reversal of the neuronal
      inhibition produced by prior injection of 8-OH-DPAT and as a shift in the potency
      of 8-OH-DPAT following p-MPPI pretreatment. Overall, these results in behaving
      animals indicate that p-MPPI acts as an effective 5-HT1A autoreceptor antagonist.
      The increase in firing rate produced by p-MPPI supports the hypothesis that
      autoreceptor-mediated feedback inhibition operates under physiological
      conditions.

PMID- 9774247
TI  - Effects of anticonvulsive drugs on pentylenetetrazol kindling and long-term
      potentiation in freely moving rats.
AB  - Drugs with anticonvulsive properties and different mechanisms of action were
      compared for their influence on long-term potentiation and pentylenetetrazol
      kindling in freely moving animals. Rats were chronically implanted with a
      stimulation electrode in the angular bundle and a recording electrode in the
      dentate gyrus. Field potentials in the dentate gyrus were elicited and long-term
      potentiation was induced by stimulation of the perforant pathway. The clinically
      used drugs or the potentially anticonvulsive drugs, diphenylhydantoin (50 mg/kg),
      diazepam (0.5 mg/kg), pentobarbital (10 mg/kg), dizocilpine (MK 801, 0.2 mg/kg)
      and CGP 43487 (2-amino-4-methyl-5-phosphono-3-pentenoic acid-carboxyethylester,
      10 mg/kg), were injected before tetanization. In behavioural experiments
      pentylenetetrazol kindling was performed with pretreatment with the substances in
      dosages indicated above (except MK 801, 0.3 mg/kg). Field potentials recorded in
      the interval between drug administration and tetanization were influenced only by
      diphenylhydantoin which enhanced the population spike amplitude to 128% of
      control values. However, the substances showed different effects on long-term
      potentiation. MK 801, CGP 43487 and pentobarbital depressed potentiation;
      diazepam was without effect. Diphenylhydantoin had a minor influence on induction
      but significantly impaired maintenance of long-term potentiation. Furthermore, MK
      801, CGP 43487, diazepam and pentobarbital differentially depressed kindling
      whereas phenytoin only slightly influenced it. The consequences as to
      hypothetical common cellular mechanisms for kindling development and long-term
      potentiation are discussed.

PMID- 9774248
TI  - The cataleptogenic effects of the neuroleptic nemonapride are attenuated by its 5
      HT1A receptor agonist properties.
AB  - The effects of the 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1
      piperazinyl]ethyl]-N-(2-pyridinyl)-cycloh exanecarboxamide (WAY 100635) on
      catalepsy induced by the dopamine D2-like receptor antagonist/5-HT1A receptor
      agonist nemonapride were examined and compared to its effects on catalepsy
      induced by neuroleptics that have low affinity for 5-HT1A receptors. Nemonapride
      induced catalepsy in both cross-legged position and bar tests at low, but not at
      high doses. Pretreatment with WAY 100635 (0.63 mg/kg) reinstated catalepsy at
      higher doses of nemonapride, indicating that the 5-HT1A receptor agonist
      properties of nemonapride are responsible for its inability to produce catalepsy
      at high doses. Additionally, WAY 100635 enhanced significantly the effects of low
      doses of nemonapride, and of the dopamine D2-like receptor antagonists raclopride
      and haloperidol. The present data indicate that the 5-HT1A receptor agonist
      properties of nemonapride attenuate its ability to induce catalepsy at higher
      doses, and suggest further that tonic 5-HT1A receptor activation may modulate
      neuroleptic-induced catalepsy.

PMID- 9774249
TI  - SB 211475, a metabolite of carvedilol, reduces infarct size after myocardial
      ischemic and reperfusion injury in rabbits.
AB  - The aim of this study was to investigate the effect of SB 211475, a metabolite of
      carvedilol with weak alpha1-adrenoceptor antagonism and antioxidant effect, on
      myocardial reperfusion injury and infarct size in anesthetized rabbits. The
      rabbits were subjected to 60 min of regional myocardial ischemia and 180 min of
      reperfusion. SB 211475 was administered either as 0.3, 1.0 or 3.0 mg/kg and
      compared to vehicle and carvedilol (1 mg/kg) treated animals. The lowest dose of
      SB 211475 (0.3 mg/kg) did not reduce infarct size compared to vehicle, whereas SB
      211475 1.0 or 3.0 mg/kg reduced infarct size significantly compared to vehicle
      (41.2 +/- 2.2% and 40.5 +/- 2.8% vs. 59.1 +/- 3.9%, p < 0.05). Carvedilol reduced
      infarct size significantly more than SB 211475 1.0 and 3.0 mg/kg (28.8 +/- 3.9%
      vs. 41.2 +/- 2.2% and 40.5 +/- 2.7%, p < 0.05). Carvedilol and SB 211475 1.0 and
      3.0 mg/kg reduced myeloperoxidase activity to the same extent, indicative of
      reduced inflammation. Rate-pressure product did not differ between doses of SB
      211475. In conclusion, SB 211475 in the two highest doses reduced infarct size by
      protecting from reperfusion injury, possibly by reduced neutrophil accumulation.
      The superior cardiac protective effect of carvedilol over SB 211475 are most
      likely due to its adrenergic pharmacology including non-selective beta- and
      alpha1-adrenoceptor antagonism.

PMID- 9774250
TI  - The role of adenosine in rat coronary flow regulation during respiratory and
      metabolic acidosis.
AB  - The role of adenosine in rat coronary flow regulation during acidosis was
      evaluated in isolated, perfused, Langendorff rat heart preparations exposed to
      brief periods of hypercapnic or metabolic acidosis. Acidosis resulted in
      increases in coronary flow rate, in conjunction with decreases in ventricular
      contractile tensions. Heart rates were non-significantly increased. Two non
      selective adenosine antagonists, caffeine and 8-phenyltheophylline, markedly
      attenuated the increases in coronary flow during hypercapnic acidosis without
      affecting the decline in contractile tension or the heart rate. ZM 241385 (4-(2
      [7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a]triazin-5-ylami no]ethyl)phenol), a
      selective adenosine A2A receptor antagonist, also blocked hypercapnic acidosis
      evoked coronary flow rate increases. The adenosine A1 selective antagonist, 8
      cyclopentyl-1,3-dipropylxanthine, did not affect flow rate increases during
      hypercapnic acidosis. SCH 58261 (5-amino-7-(2-phenyl ethyl)-2-(2-furyl)pyrazolo
      [4,3-e]-1,2,4-triazolo[1,5-c] pyrimidine, a selective adenosine A2A receptor
      antagonist, blocked the increases in coronary flow rate evoked by metabolic
      acidosis. An adenosine transport inhibitor, dipyridamole, doubled coronary flow
      rates during hypercapnic acidosis. When taken in conjunction with previous
      reports that acidosis enhances adenosine release from cardiac preparations, these
      results suggest that adenosine is a significant contributor to acidosis-evoked
      increases in coronary flow.

PMID- 9774251
TI  - Inhibition of long-chain fatty acid metabolism does not affect platelet
      aggregation responses.
AB  - A number of anti-anginal agents (perhexiline, amiodarone, trimetazidine) have
      been shown to inhibit myocardial carnitine palmitoyltransferase-1, which controls
      access of long-chain fatty acids to mitochondrial sites of beta-oxidation. In
      view of clinical data suggesting that perhexiline improves symptomatic status in
      unstable angina pectoris, and the known role of mitochondrial beta-oxidation in
      platelet metabolism, we compared the platelet carnitine palmitoyltransferase-1
      inhibitory and putative anti-aggregatory effects of perhexiline, amiodarone and
      trimetazidine with those of specific carnitine palmitoyltransferase-1 inhibitors:
      etomoxir and hydroxyphenylglyoxylate in both normal subjects and patients with
      stable angina. All of the compounds examined inhibited platelet carnitine
      palmitoyltransferase-1 activity; rank order of potency etomoxir > malonyl-CoA >
      hydroxyphenylglyoxylate > amiodarone > or = perhexiline > trimetazidine. However,
      only perhexiline, amiodarone and trimetazidine inhibited platelet aggregation. We
      conclude that (a) the carnitine palmitoyltransferase-1 inhibitors perhexiline,
      amiodarone and trimetazidine exert significant anti-aggregatory effects which may
      be therapeutically relevant and, (b) these effects are independent of carnitine
      palmitoyltransferase-1 inhibition.

PMID- 9774253
TI  - Inhibitory actions of various vasorelaxants on the myogenic contraction induced
      by quick stretch studied in canine cerebral artery.
AB  - Quick stretch at a rate of 10 cm/s with the amount of 30% of the initial muscle
      length (= 100%) produced a myogenic contraction in canine cerebral artery. The
      inhibitory actions of various vasorelaxants on the stretch-induced contraction
      were investigated. Ca2+ channel blockers (nicardipine, D-cis-diltiazem) inhibited
      the stretch-induced contraction by 50-60% at the concentrations which abolished
      high KCl-induced contraction. Inhibitions of the stretch-induced contraction by
      nitro-compounds (nitroglycerin, sodium nitroprusside) were about 50%. In
      contrast, inhibitions by the compounds which activate ATP-sensitive K+ channels
      (cromakalim, nicorandil, pinacidil) of the myogenic contraction in response to
      quick stretch were only 20%. Papaverine totally abolished the stretch-induced
      contraction. It is likely that all the vasorelaxant compounds tested in the
      present study except papaverine are beneficial in the sense that they do not
      suppress the intrinsic myogenic contraction, which may be related to the
      autoregulation of local blood flow.

PMID- 9774252
TI  - Evidence that Ca2+-activated K+ channels play a major role in mediating the
      vascular effects of iloprost and cicaprost.
AB  - The role of K+ channels in mediating vasorelaxation induced by two prostacyclin
      analogues was investigated in guinea-pig aorta. Iloprost caused substantial
      relaxation of tissues contracted with phenylephrine or 25 mM K+ but not 60 mM K+.
      In endothelial-denuded tissues, maximal relaxations to iloprost, cicaprost or
      isoprenaline were inhibited by approximately 40-50% with tetraethylammonium or
      iberiotoxin, both blockers of large conductance Ca2+-activated K+ (BKCa)
      channels. In contrast, the response to forskolin, an activator of adenylate
      cyclase was marginally inhibited by tetraethylammonium. The K(ATP) channel
      blocker, glibenclamide significantly augmented the response to iloprost but not
      cicaprost. These effects were largely inhibited by the EP1 receptor antagonist, 8
      chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid 2-[1-oxo-3(4
      pyridinyl)propyl]hydrazide, monohydrochloride (SC-51089) and partially by
      indomethacin, suggesting that iloprost relaxation is counterbalanced by
      activation of EP1 receptors, in part through a constrictor prostaglandin. We
      conclude that BKCa channels play an important role in mediating the effects of
      iloprost and cicaprost and raises the possibility that cyclic AMP-independent
      pathways might be involved.

PMID- 9774254
TI  - Effects of arachidonic acid metabolism on hypoxic vasoconstriction in rabbit
      lungs.
AB  - Hypoxic pulmonary vasoconstriction is an essential mechanism that matches lung
      perfusion to ventilation, thus optimising pulmonary gas exchange. Despite its
      pathophysiological relevance, the mechanism of hypoxic pulmonary vasoconstriction
      still remains enigmatic. We investigated whether arachidonic acid metabolism is
      involved in the regulation of hypoxic pulmonary vasoconstriction in isolated,
      buffer-perfused rabbit lungs. Seven inhibitors were employed to determine the
      contribution of different vasoactive lipoxy- and cyclooxygenase mediators as well
      as cytochrome P450 products on the magnitude of hypoxic pulmonary
      vasoconstriction. Hypoxic pulmonary vasoconstriction was not affected by (i) the
      cyclooxygenase inhibitor acetylsalicylic acid, (ii) the thromboxane A2 receptor
      antagonist BM13.505, (iii) the 5'-lipoxygenase inhibitor MK886, and (iv) the
      lipoxygenase and cyclooxygenase inhibitor BW755c. The hypoxia-elicited pressor
      response was prominently inhibited by (i) nordihydroguaiaretic acid (50-150
      microM), an inhibitor of lipoxygenase and cyclooxygenase and (ii) methoxsalen
      (100 microM) and 1-aminobenzotriazole (1-10 mM), two inhibitors of cytochrome
      P450-derived metabolites. However, no specificity for the regulation of hypoxic
      pulmonary vasoconstriction was found, as corresponding inhibitory potency of
      these agents was noted when vasoconstriction was achieved by the stable
      thromboxane analogue U46619 under conditions of normoxia. We conclude that there
      is no evidence for a specific involvement of different pathways of arachidonic
      acid metabolism in the mechanism of hypoxic pulmonary vasoconstriction in
      rabbits.

PMID- 9774255
TI  - Inhibition by the anti-mitotic drug doxorubicin of platelet-activating-factor
      induced late eosinophil accumulation in rats.
AB  - Platelet-activating factor (PAF) has been shown, in the rat model of pleural
      inflammation, to induce the generation of an intermediate proteic factor able to
      cause eosinophil proliferation in vitro. This study was undertaken to investigate
      the effect of the anti-mitotic compound doxorubicin on PAF-induced eosinophilia
      in rats, in order to evaluate the contribution of local cell proliferation to
      this phenomenon. The late eosinophil infiltration caused by another
      chemoattractant leukotriene B4 was used for comparison. We observed that local
      treatment with doxorubicin (20 and 40 microg/cavity), given 6 h after PAF (1
      microg/cavity), suppressed the eosinophil accumulation within 24 h, whilst only
      the higher dose was effective when the drug was given 12 h post-PAF. An effect on
      chemotaxis was ruled out, since local doxorubicin (40 microg/cavity) failed to
      modify the eosinophil migration noted 24 h after leukotriene B4 (0.5
      microg/cavity) and the neutrophil/eosinophil infiltration noted at 6 h after PAF
      injection. Transfer of the pleural fluids collected 6 h after PAF from donors to
      recipient rats caused significant eosinophil accumulation in the recipient rats,
      an effect which was inhibited by the co-administration of doxorubicin (40
      microg/cavity). No inhibitory effect was noted when the drug was given 6 h after
      the pleural fluids were transferred. We also found no change in the number of
      blood or bone marrow eosinophils after PAF stimulation. We conclude that
      doxorubicin selectively impaired the late eosinophil accumulation triggered by
      PAF in the pleural cavity of rats, clearly indicating that local cell
      proliferation seems to contribute to the development of this inflammatory
      response.

PMID- 9774256
TI  - Role of tumour necrosis factor-alpha and inducible nitric oxide synthase in the
      prevention of nitro-flurbiprofen small intestine toxicity.
AB  - The present study compares the intestinal toxicity of nitro-flurbiprofen and
      flurbiprofen in order to determine their differential properties on tumour
      necrosis factor-alpha production and inducible nitric oxide synthase induction.
      Rats received one s.c. injection of flurbiprofen, nitro-flurbiprofen at equimolar
      dose of solvent. Twenty-four hours later, the rats were sacrificed and small
      intestine tissue was taken up for macroscopical quantification of ulceration, ex
      vivo production of tumour necrosis factor-alpha and nitrites, and determination
      of tissue inducible nitric oxide synthase and myeloperoxidase activities. Anti
      inflammatory activity was examined in the carrageenan-induced paw edema model. We
      demonstrated that flurbiprofen induced dose-dependently small intestine
      production of tumour necrosis factor-alpha, nitrites, myeloperoxidase and
      inducible nitric oxide synthase activities. On the other hand, nitro-flurbiprofen
      did neither induce tumour necrosis factor-alpha nor nitrite production.
      Concurrently, no small intestine ulceration was observed with nitro-flurbiprofen
      whereas flurbiprofen induced dose-dependent ulceration. Nitro-flurbiprofen is
      devoid of intestinal toxicity despite inhibiting cyclooxygenase activity. This is
      associated with the absence of tumour necrosis factor-alpha and inducible nitric
      oxide synthase induction in normal rats. Nitro-flurbiprofen is an anti
      inflammatory drug with a much more favorable gastro-intestinal toxicity profile
      than flurbiprofen.

PMID- 9774257
TI  - Sustained exposure to a glycine receptor partial agonist differentially alters
      NMDA receptor agonist and antagonist potencies in cultured spinal cord neurons.
AB  - Sustained (20 h) exposure to the glycine partial agonist 1
      aminocyclopropanecarboxylic acid (ACPC) significantly reduced N-methyl-D
      aspartate (NMDA)-induced neurotoxicity in cultured spinal cord neurons when the
      NMDA (25 and 100 microM) was added to the cultures 30 min after removal of the
      ACPC (1 mM). In contrast, ACPC preexposure failed to protect against kainate
      induced neuronal injury. The magnitude of neuronal protection against NMDA (100
      microM) was further enhanced if the neurons pretreated with ACPC were reexposed
      to this drug during the NMDA challenge. In addition, the potencies of both the
      competitive NMDA antagonist AP5 and the noncompetitive antagonist dizocilpine to
      block NMDA toxicity were significantly increased following ACPC preexposure,
      while the potency of the competitive glycine receptor antagonist 7
      chlorokynurenate (7-CK) was unchanged. Analysis of Northern blots suggest that
      ACPC-induced changes in NMDA receptor function were not associated with
      alterations in the levels of the mRNAs encoding the NMDAR-1, -2A, -2B, or -2C
      subunits. These results indicate that sustained exposure to ACPC modifies NMDA
      receptors in a manner that diminishes NMDA receptor-mediated neurotoxicity while
      selectively enhancing the potencies of several NMDA receptor antagonists. These
      effects do not appear to be related to changes in expression of specific NMDA
      receptor subunits, and may instead involve a post-translational modification of
      one or more subunit proteins.

PMID- 9774258
TI  - The electrical and mechanical response of adult guinea pig and rat ventricular
      myocytes to omega3 polyunsaturated fatty acids.
AB  - Single adult guinea-pig and rat ventricular cardiac myocytes were used to study
      the effects of two members of the omega3 class of polyunsaturated fatty acids,
      docosahexaenoic acid and eicosapentaenoic acid, on the electrical and mechanical
      activity of cardiac muscle. Docosahexaenoic acid and eicosapentaenoic acid
      reduced the electrical excitability of both guinea-pig and rat cells in a dose
      dependent manner. Both agents produced a dose-dependent negative inotropic
      response in guinea-pig cells but in the rat cells there was first a dose
      dependent positive inotropic effect at low concentrations (< 10 microM) followed
      by a negative inotropic effect at higher concentrations (> 10 microM). Possible
      mechanisms by which these agents affect contraction were studied using
      conventional electrophysiological techniques. The polyunsaturated fatty acids
      reduced the action potential duration and the plateau potential of the guinea-pig
      cells in a simple, dose-dependent manner. In contrast, the effect on the rat
      action potential mirrored the inotropic effect. At low concentrations (< 10
      microM) there was a concentration-dependent increase in action potential duration
      followed by a concentration-dependent decrease at higher concentrations (> 10
      microM). Both polyunsaturated fatty acids decreased the fast Na+ current and the
      L-type Ca2+ current in a concentration-dependent but not use-dependent manner in
      cells from both species. In the rat cells these agents inhibited the transient
      outward current resulting in an increase in the duration of the rat action
      potential. The effects of polyunsaturated fatty acids on the Ca2+, Na+ and K+
      currents underlie these changes in the action potentials in guinea-pig and rat
      heart cells. The effects on the L-type Ca2+ current and action potential duration
      can also explain both the simple negative inotropic effects of the agents on the
      guinea-pig cells and the more complex effects on the rat cells. These effects of
      polyunsaturated fatty acids on membrane currents may account for their anti
      arrhythmic properties.

PMID- 9774259
TI  - Selective activation of group-II metabotropic glutamate receptors is protective
      against excitotoxic neuronal death.
AB  - Aminopyrrolidine-2R,4R-dicarboxylated (2R,4R-APDC) has recently been introduced
      as a potent and highly selective agonist of metabotropic glutamate (mGlu)
      receptor subtypes mGlu2 and -3. In murine cortical cultures containing both
      neurons and astrocytes, 2R,4R-APDC attenuated the delayed neuronal degeneration
      induced by a 10-min pulse of N-methyl-D-aspartate (NMDA). 2R,4R-APDC was
      maximally neuroprotective in a range of concentrations (0.1-1 microM) comparable
      to that reported for the activation of mGlu2 or -3 receptors in heterologous
      expression systems. The action of 2R,4R-APDC was sensitive to the mGlu2/3
      receptor antagonists, (2S)-alpha-ethylglutamate and (2S,1S',2S',3R')-2-(2'
      carboxy-3'-phenylcyclopropyl)glycine. These results indicate that activation of
      mGlu2 and/or -3 receptors is sufficient per se to protect neurons against
      excitotoxic degeneration, and encourage the search for potent, selective and
      systemically active mGlu2/3 receptor agonists as neuroprotective drugs.

PMID- 9774261
TI  - Carbon dioxide emission from european estuaries 
AB  - The partial pressure of carbon dioxide (pCO2) in surface waters and related
      atmospheric exchanges were measured in nine European estuaries. Averaged fluxes
      over the entire estuaries are usually in the range of 0.1 to 0.5 mole of CO2 per
      square meter per day. For wide estuaries, net daily fluxes to the atmosphere
      amount to several hundred tons of carbon (up to 790 tons of carbon per day in the
      Scheldt estuary). European estuaries emit between 30 and 60 million tons of
      carbon per year to the atmosphere, representing 5 to 10% of present anthropogenic
      CO2 emissions for Western Europe.

PMID- 9774260
TI  - Nocistatin reverses nociceptin inhibition of glutamate release from rat brain
      slices.
AB  - We have examined the effects of the recently described heptadecapeptide
      nocistatin on K+-evoked glutamate release from rat cerebrocortical slices in
      vitro. In vivo, nocistatin reverses the action of nociceptin. Nocistatin (100 nM,
      n = 7) did not inhibit K+-evoked glutamate release alone. Nociceptin (100 nM)
      inhibited glutamate release by 51.7 +/- 8.3% (P < 0.05, n = 6) and this was fully
      reversed by nocistatin (100 nM). Nocistatin also appears to be an antagonist of
      nociceptin action in vitro.

PMID- 9774262
TI  - A short circuit in thermohaline circulation: A cause for northern hemisphere
      glaciation? 
AB  - The cause of Northern Hemisphere glaciation about 3 million years ago remains
      uncertain. Closing the Panamanian Isthmus increased thermohaline circulation and
      enhanced moisture supply to high latitudes, but the accompanying heat would have
      inhibited ice growth. One possible solution is that enhanced moisture transported
      to Eurasia also enhanced freshwater delivery to the Arctic via Siberian rivers.
      Freshwater input to the Arctic would facilitate sea ice formation, increase the
      albedo, and isolate the high heat capacity of the ocean from the atmosphere. It
      would also act as a negative feedback on the efficiency of the "conveyor belt"
      heat pump.

PMID- 9774263
TI  - Changes in the carbon balance of tropical forests: evidence from long-term plots 
AB  - The role of the world's forests as a "sink" for atmospheric carbon dioxide is the
      subject of active debate. Long-term monitoring of plots in mature humid tropical
      forests concentrated in South America revealed that biomass gain by tree growth
      exceeded losses from tree death in 38 of 50 Neotropical sites. These forest plots
      have accumulated 0.71 ton, plus or minus 0.34 ton, of carbon per hectare per year
      in recent decades. The data suggest that Neotropical forests may be a significant
      carbon sink, reducing the rate of increase in atmospheric carbon dioxide.

PMID- 9774264
TI  - A large terrestrial carbon sink in north america implied by atmospheric and
      oceanic carbon dioxide data and models 
AB  - Atmospheric carbon dioxide increased at a rate of 2.8 petagrams of carbon per
      year (Pg C year-1) during 1988 to 1992 (1 Pg = 10(15) grams). Given estimates of
      fossil carbon dioxide emissions, and net oceanic uptake, this implies a global
      terrestrial uptake of 1.0 to 2. 2 Pg C year-1. The spatial distribution of the
      terrestrial carbon dioxide uptake is estimated by means of the observed spatial
      patterns of the greatly increased atmospheric carbon dioxide data set available
      from 1988 onward, together with two atmospheric transport models, two estimates
      of the sea-air flux, and an estimate of the spatial distribution of fossil carbon
      dioxide emissions. North America is the best constrained continent, with a mean
      uptake of 1.7 +/- 0.5 Pg C year-1, mostly south of 51 degrees north. Eurasia
      North Africa is relatively weakly constrained, with a mean uptake of 0.1 +/- 0.6
      Pg C year-1. The rest of the world's land surface is poorly constrained, with a
      mean source of 0.2 +/- 0.9 Pg C year-1.

PMID- 9774265
TI  - North atlantic oscillation dynamics recorded in greenland ice cores 
AB  - Carefully selected ice core data from Greenland can be used to reconstruct an
      annual proxy North Atlantic oscillation (NAO) index. This index for the past 350
      years indicates that the NAO is an intermittent climate oscillation with
      temporally active (coherent) and passive (incoherent) phases. No indication for a
      single, persistent, multiannual NAO frequency is found. In active phases, most of
      the energy is located in the frequency band with periods less than about 15
      years. In addition, variability on time scales of 80 to 90 years has been
      observed since the mid-19th century.

PMID- 9774266
TI  - Two-dimensional magnetic particles 
AB  - Single two-dimensional (2D) atomically thick magnetic particles of cobalt and
      iron with variable size and shape were fabricated by combining a mask technique
      with standard molecular beam epitaxy. Reduction of the lateral size of in-plane
      magnetized 2D cobalt films down to about 100 nanometers did not essentially
      modify their magnetic properties; although the separation of boundaries decreased
      greatly, neither domain penetrated the particle, nor was any sizable shape
      anisotropy observed. The mutual interaction of 2D cobalt particles was
      negligible, and the magnetic state of a single particle could be switched without
      modifying the state of the neighbors. Perpendicularly magnetized iron particles
      did not exhibit such responses. These results suggest that only a few atoms
      forming a 2D in-plane magnetized dot may provide a stable elementary bit for
      nanorecording.

PMID- 9774267
TI  - Oxygen reservoirs in the early solar nebula inferred from an allende CAI 
AB  - Ultraviolet laser microprobe analyses of a calcium-aluminum-rich inclusion (CAI)
      from the Allende meteorite suggest that a line with a slope of exactly 1.00 on a
      plot of delta17O against delta18O represents the primitive oxygen isotope
      reservoir of the early solar nebula. Most meteorites are enriched in 17O and 18O
      relative to this line, and their oxygen isotope ratios can be explained by mass
      fractionation or isotope exchange initiating from the primitive reservoir. These
      data establish a link between the oxygen isotopic composition of the abundant
      ordinary chondrites and the primitive 16O-rich component of CAIs.

PMID- 9774268
TI  - Antarctic elevation change from 1992 to 1996 
AB  - Satellite radar altimeter measurements show that the average elevation of the
      Antarctic Ice Sheet interior fell by 0.9 +/- 0.5 centimeters per year from 1992
      to 1996. If the variability of snowfall observed in Antarctic ice cores is
      allowed for, the mass imbalance of the interior this century is only -0.06 +/-
      0.08 of the mean mass accumulation rate.

PMID- 9774269
TI  - Migration of fluids beneath yellowstone caldera inferred from satellite radar
      interferometry 
AB  - Satellite interferometric synthetic aperture radar is uniquely suited to
      monitoring year-to-year deformation of the entire Yellowstone caldera (about 3000
      square kilometers). Sequential interferograms indicate that subsidence within the
      caldera migrated from one resurgent dome to the other between August 1992 and
      August 1995. Between August 1995 and September 1996, the caldera region near the
      northeast dome began to inflate, and accompanying surface uplift migrated to the
      southwest dome between September 1996 and June 1997. These deformation data are
      consistent with hydrothermal or magmatic fluid migration into and out of two sill
      like bodies that are about 8 kilometers directly beneath the caldera.

PMID- 9774270
TI  - Induced massive star formation in the trifid nebula? 
AB  - The Trifid nebula is a young (10(5) years) galactic HII region where several
      protostellar sources have been detected with the infrared space observatory. The
      sources are massive (17 to 60 solar masses) and are associated with molecular gas
      condensations at the edges or inside the nebula. They appear to be in an early
      evolutionary stage and may represent the most recent generation of stars in the
      Trifid. These sources range from dense, apparently still inactive cores to more
      evolved sources, undergoing violent mass ejection episodes, including a source
      that powers an optical jet. These observations suggest that the protostellar
      sources may have evolved by induced star formation in the Trifid nebula.

PMID- 9774271
TI  - Exceeding 5000-fold concentration of dilute analytes in micellar electrokinetic
      chromatography.
AB  - When a neutral analyte zone is injected into a charged pseudostationary phase,
      the length of the zone is predicted to be narrowed by 1/(1 + k), where k is the
      retention factor. The conditions for zone narrowing to occur assume negligible
      electroosmotic flow, a relatively constant electric field along the capillary
      column, and no pseudostationary phase in the injected analyte mixture. The
      theoretically expected concentration enhancement was demonstrated experimentally.
      Consequently, the detection sensitivity of analytes in micellar electrokinetic
      chromatography (MEKC) can be improved significantly. For example, 9 to 18 parts
      per billion of an environmentally important racemic herbicide spiked in lake
      water was separated by MEKC and detected by ultraviolet absorption.

PMID- 9774273
TI  - Host-race formation in the common cuckoo 
AB  - The exploitation of a new host by a parasite may result in host-race formation or
      speciation. A brood parasitic bird, the common cuckoo, is divided into host
      races, each characterized by egg mimicry of different host species.
      Microsatellite DNA markers were used to examine cuckoo mating patterns and host
      usage in an area where a new host has been recently colonized. Female cuckoos
      show strong host preferences, but individual males mate with females that lay in
      the nests of different hosts. Female host specialization may lead to the
      evolution of sex-linked traits such as egg mimicry, even though gene flow through
      the male line prevents completion of the speciation process.

PMID- 9774272
TI  - Increased vascularization in mice overexpressing angiopoietin-1.
AB  - The angiopoietins and members of the vascular endothelial growth factor (VEGF)
      family are the only growth factors thought to be largely specific for vascular
      endothelial cells. Targeted gene inactivation studies in mice have shown that
      VEGF is necessary for the early stages of vascular development and that
      angiopoietin-1 is required for the later stages of vascular remodeling. Here it
      is shown that transgenic overexpression of angiopoietin-1 in the skin of mice
      produces larger, more numerous, and more highly branched vessels. These results
      raise the possibility that angiopoietins can be used, alone or in combination
      with VEGF, to promote therapeutic angiogenesis.

PMID- 9774274
TI  - Killer whale predation on sea otters linking oceanic and nearshore ecosystems 
AB  - After nearly a century of recovery from overhunting, sea otter populations are in
      abrupt decline over large areas of western Alaska. Increased killer whale
      predation is the likely cause of these declines. Elevated sea urchin density and
      the consequent deforestation of kelp beds in the nearshore community demonstrate
      that the otter's keystone role has been reduced or eliminated. This chain of
      interactions was probably initiated by anthropogenic changes in the offshore
      oceanic ecosystem.

PMID- 9774275
TI  - Induction of antigen-specific cytotoxic T lymphocytes in humans by a malaria DNA
      vaccine.
AB  - CD8+ cytotoxic T lymphocytes (CTLs) are critical for protection against
      intracellular pathogens but often have been difficult to induce by subunit
      vaccines in animals. DNA vaccines elicit protective CD8+ T cell responses.
      Malaria-naive volunteers who were vaccinated with plasmid DNA encoding a malaria
      protein developed antigen-specific, genetically restricted, CD8+ T cell-dependent
      CTLs. Responses were directed against all 10 peptides tested and were restricted
      by six human lymphocyte antigen (HLA) class I alleles. This first demonstration
      in healthy naive humans of the induction of CD8+ CTLs by DNA vaccines, including
      CTLs that were restricted by multiple HLA alleles in the same individual,
      provides a foundation for further human testing of this potentially revolutionary
      vaccine technology.

PMID- 9774276
TI  - Differentiation of monocytes into dendritic cells in a model of transendothelial
      trafficking.
AB  - Essential to the dendritic cell system of antigen-presenting cells are the veiled
      dendritic cells that traverse afferent lymph to enter lymph nodes, where they
      initiate immune responses. The origin of veiled cells, which were discovered 20
      years ago, is unclear. Monocytes cultured with endothelium differentiated into
      dendritic cells within 2 days, particularly after phagocytosing particles in
      subendothelial collagen. These nascent dendritic cells migrated across the
      endothelium in the ablumenal-to-lumenal direction, as would occur during entry
      into lymphatics. Monocytes that remained in the subendothelial matrix became
      macrophages. Therefore, monocytes have two potential fates associated with
      distinct patterns of migration.

PMID- 9774277
TI  - An integrated nanoliter DNA analysis device.
AB  - A device was developed that uses microfabricated fluidic channels, heaters,
      temperature sensors, and fluorescence detectors to analyze nanoliter-size DNA
      samples. The device is capable of measuring aqueous reagent and DNA-containing
      solutions, mixing the solutions together, amplifying or digesting the DNA to form
      discrete products, and separating and detecting those products. No external
      lenses, heaters, or mechanical pumps are necessary for complete sample processing
      and analysis. Because all of the components are made using conventional
      photolithographic production techniques, they operate as a single closed system.
      The components have the potential for assembly into complex, low-power,
      integrated analysis systems at low unit cost. The availability of portable,
      reliable instruments may facilitate the use of DNA analysis in applications such
      as rapid medical diagnostics and point-of-use agricultural testing.

PMID- 9774278
TI  - Phosphorylation and activation of 13S condensin by Cdc2 in vitro.
AB  - 13S condensin is a multisubunit protein complex essential for mitotic chromosome
      condensation in Xenopus egg extracts. Purified 13S condensin introduces positive
      supercoils into DNA in the presence of topoisomerase I and adenosine triphosphate
      in vitro. The supercoiling activity of 13Scondensin was regulated by mitosis
      specific phosphorylation. Immunodepletion, in vitro phosphorylation, and peptide
      mapping experiments indicated that Cdc2 is likely to be the kinase that
      phosphorylates and activates 13S condensin. Multiple Cdc2 phosphorylation sites
      are clustered in the carboxyl-terminal domain of the XCAP-D2 (Xenopus chromosome
      associated polypeptide D2) subunit. These results suggest that phosphorylation of
      13Scondensin by Cdc2 may trigger mitotic chromosome condensation in vitro.

PMID- 9774279
TI  - Inhibition of toxic epidermal necrolysis by blockade of CD95 with human
      intravenous immunoglobulin.
AB  - Toxic epidermal necrolysis (TEN, Lyell's syndrome) is a severe adverse drug
      reaction in which keratinocytes die and large sections of epidermis separate from
      the dermis. Keratinocytes normally express the death receptor Fas (CD95); those
      from TEN patients were found to express lytically active Fas ligand (FasL).
      Antibodies present in pooled human intravenous immunoglobulins (IVIG) blocked Fas
      mediated keratinocyte death in vitro. In a pilot study, 10 consecutive
      individuals with clinically and histologically confirmed TEN were treated with
      IVIG; disease progression was rapidly reversed and the outcome was favorable in
      all cases. Thus, Fas-FasL interactions are directly involved in the epidermal
      necrolysis of TEN, and IVIG may be an effective treatment.

PMID- 9774281
TI  - Severe mental illness in prisoners: a persistent problem that needs a concerted
      and long term response.

PMID- 9774280
TI  - Two modes of survival of fission yeast without telomerase.
AB  - Deletion of the telomerase catalytic subunit gene trt1+ in Schizosaccharomyces
      pombe results in death for the majority of cells, but a subpopulation survives.
      Here it is shown that most survivors have circularized all of their chromosomes,
      whereas a smaller number maintain their telomeres presumably through
      recombination. When the telomeric DNA-binding gene taz1+ is also deleted, trt1-
      taz1- survivors use the recombinational mode more frequently. Moreover, the
      massive elongation of telomeres in taz1- cells is absent in the double mutant.
      Thus, Taz1p appears to regulate telomeric recombination as well as telomerase
      activity in fission yeast.

PMID- 9774282
TI  - NHS direct: evaluate, integrate, or bust.

PMID- 9774283
TI  - Changing practice in maternity care: it's hard to know what works.

PMID- 9774284
TI  - Sticks and stones: changing terminology is no substitute for good consultation
      skills.

PMID- 9774285
TI  - Fluoroquinolone resistance: overuse of fluoroquinolones in human and veterinary
      medicine can breed resistance.

PMID- 9774286
TI  - D-dimer testing as an adjunct to ultrasonography in patients with clinically
      suspected deep vein thrombosis: prospective cohort study. The Multicentre Italian
      D-dimer Ultrasound Study Investigators Group.
AB  - OBJECTIVE: To investigate the efficacy of using a rapid plasma D-dimer test as an
      adjunct to compression ultrasound for diagnosing clinically suspected deep vein
      thrombosis. DESIGN: D-dimer concentrations were determined in all patients with a
      normal ultrasonogram at presentation. Repeat ultrasonography was performed 1 week
      later only in patients with abnormal D-dimer test results. MAIN OUTCOME AND
      MEASURES: Patients with normal ultrasonograms were not treated with
      anticoagulants and were followed for 3 months for thromboembolic complications.
      SETTING: University research and affiliated centres. SUBJECTS: 946 patients with
      clinically suspected deep vein thrombosis. RESULTS: Ultrasonograms were abnormal
      at presentation in 260 (27.5%) patients. Of the remaining 686 patients tested for
      D-dimer, 88 (12.8%) had abnormal concentrations. During follow up venous
      thromboembolic complications occurred in one of the 598 patients who were not
      treated with anticoagulants and who had an initial normal ultrasonogram and D
      dimer concentration, whereas thromboembolic complications occurred in two of the
      83 untreated patients who had abnormal D-dimer concentrations but a normal repeat
      ultrasonogram. The cumulative incidence of venous thromboembolic complications
      during follow up was 0.4% (95% confidence interval 0% to 0.9%). The rapid plasma
      D-dimer test used as an adjunct to compression ultrasonography resulted in a
      reduction in the mean number of repeat ultrasound examinations and additional
      hospital visits from 0.7 to 0.1 per patient. CONCLUSIONS: Testing for D-dimer as
      an adjunct to a normal baseline ultrasound examination decreased the number of
      subsequent ultrasound examinations considerably without any increased risk of
      venous thromboembolic complications in patients not receiving anticoagulants. The
      use of ultrasound and testing for D-dimer enabled treatment decisions to be made
      at the time of presentation in most patients.

PMID- 9774287
TI  - Randomised trial of educational visits to enhance use of systematic reviews in 25
      obstetric units.
AB  - OBJECTIVE: To evaluate the effectiveness of an educational visit to help
      obstetricians and midwives select and use evidence from a Cochrane database
      containing 600 systematic reviews. DESIGN: Randomised single blind controlled
      trial with obstetric units allocated to an educational visit or control group.
      SETTING: 25 of the 26 district general obstetric units in two former NHS regions.
      SUBJECTS: The senior obstetrician and midwife from each intervention unit
      participated in educational visits. Clinical practices of all staff were assessed
      in 4508 pregnancies. INTERVENTION: Single informal educational visit by a
      respected obstetrician including discussion of evidence based obstetrics,
      guidance on implementation, and donation of Cochrane database and other
      materials. MAIN OUTCOME MEASURES: Rates of perineal suturing with polyglycolic
      acid, ventouse delivery, prophylactic antibiotics in caesarean section, and
      steroids in preterm delivery, before and 9 months after visits, and concordance
      of guidelines with review evidence for same marker practices before and after
      visits. RESULTS: Rates varied greatly, but the overall baseline mean of 43%
      (986/2312) increased to 54% (1189/2196) 9 months later. Rates of ventouse
      delivery increased significantly in intervention units but not in control units;
      there was no difference between the two types of units in uptake of other
      practices. Pooling rates from all 25 units, use of antibiotics in caesarean
      section and use of polyglycolic acid sutures increased significantly over the
      period, but use of steroids in preterm delivery was unchanged. Labour ward
      guidelines seldom agreed with evidence at baseline; this hardly improved after
      visits. Educational visits cost pound860 each (at 1995 prices). CONCLUSIONS:
      There was considerable uptake of evidence into practice in both control and
      intervention units between 1994 and 1995. Our educational visits added little to
      this, despite the informal setting, targeting of senior staff from two
      disciplines, and donation of educational materials. Further work is needed to
      define cost effective methods to enhance the uptake of evidence from systematic
      reviews and to clarify leadership and roles of senior obstetric staff in
      implementing the evidence.

PMID- 9774288
TI  - Use of health services by children and young people according to ethnicity and
      social class: secondary analysis of a national survey.
AB  - OBJECTIVE: To assess whether equity is achieved in use of general practitioner,
      outpatient, and inpatient services by children and young people according to
      their ethnic group and socioeconomic background. DESIGN: Secondary analysis of
      the British general household survey, 1991-94. SUBJECTS: 20 473 children and
      young people aged between 0 and 19 years. MAIN OUTCOME MEASURES: Consultations
      with a general practitioner within a two week period, outpatient attendances
      within a three month period, and inpatient stays during the past year. RESULTS:
      There were no significant class differences in the use of health services by
      children and young people, and there was little evidence of variation in use of
      health services according to housing tenure and parental work status. South Asian
      children and young people used general practitioner services more than any other
      ethnic group after controlling for socioeconomic background and perceived health
      status, but the use of hospital outpatient and inpatient services was
      significantly lower for children and young people from all minority ethnic groups
      compared with the white population. CONCLUSIONS: Our results differ from previous
      studies, which have reported significant class differences in use of health
      services for other age groups. We found no evidence that children and young
      people's use of health services varied according to their socioeconomic status,
      suggesting that equity has been achieved. A child or young person's ethnic
      origin, however, was clearly associated with use of general practitioner and
      hospital services, which could imply that children and young people from minority
      ethnic groups receive a poorer quality of health care than other children and
      young people.

PMID- 9774289
TI  - Patients' preference for male or female breast surgeons: questionnaire study.

PMID- 9774290
TI  - Factors associated with gonorrhoea in men aware of being positive for HIV
      infection: case-control study.

PMID- 9774292
TI  - Prescribing pressures 

PMID- 9774291
TI  - Vaginal viricides-another way to tackle HIV transmission.

PMID- 9774294
TI  - An oldfashioned miracle 

PMID- 9774293
TI  - Medicine in holland 

PMID- 9774296
TI  - Recent advances: medical microbiology.

PMID- 9774295
TI  - Safety and effectiveness of nurse telephone consultation in out of hours primary
      care: randomised controlled trial. The South Wiltshire Out of Hours Project
      (SWOOP) Group.
AB  - OBJECTIVE: To determine the safety and effectiveness of nurse telephone
      consultation in out of hours primary care by investigating adverse events and the
      management of calls. DESIGN: Block randomised controlled trial over a year of 156
      matched pairs of days and weekends in 26 blocks. One of each matched pair was
      randomised to receive the intervention. SETTING: One 55 member general practice
      cooperative serving 97 000 registered patients in Wiltshire. SUBJECTS: All
      patients contacting the out of hours service or about whom contact was made
      during specified times over the trial year. INTERVENTION: A nurse telephone
      consultation service integrated within a general practice cooperative. The out of
      hours period was 615 pm to 1115 pm from Monday to Friday, 1100 am to 1115 pm on
      Saturday, and 800 am to 1115 pm on Sunday. Experienced and specially trained
      nurses received, assessed, and managed calls from patients or their carers.
      Management options included telephone advice; referral to the general
      practitioner on duty (for telephone advice, an appointment at a primary care
      centre, or a home visit); referral to the emergency service or advice to attend
      accident and emergency. Calls were managed with the help of decision support
      software. MAIN OUTCOME MEASURES: Deaths within seven days of a contact with the
      out of hours service; emergency hospital admissions within 24 hours and within
      three days of contact; attendance at accident and emergency within three days of
      a contact; number and management of calls in each arm of the trial. RESULTS: 14
      492 calls were received during the specified times in the trial year (7308 in the
      control arm and 7184 in the intervention arm) concerning 10 134 patients (10.4%
      of the registered population). There were no substantial differences in the age
      and sex of patients in the intervention and control groups, though male patients
      were underrepresented overall. Reasons for calling the service were consistent
      with previous studies. Nurses managed 49.8% of calls during intervention periods
      without referral to a general practitioner. A 69% reduction in telephone advice
      from a general practitioner, together with a 38% reduction in patient attendance
      at primary care centres and a 23% reduction in home visits was observed during
      intervention periods. Statistical equivalence was observed in the number of
      deaths within seven days, in the number of emergency hospital admissions, and in
      the number of attendances at accident and emergency departments. Conclusions
      Nurse telephone consultation produced substantial changes in call management,
      reducing overall workload of general practitioners by 50% while allowing callers
      faster access to health information and advice. It was not associated with an
      increase in the number of adverse events. This model of out of hours primary care
      is safe and effective.

PMID- 9774297
TI  - The roumanian soldier and the spirit ration 

PMID- 9774298
TI  - ABC of oxygen: oxygen at high altitude.

PMID- 9774299
TI  - Rationing and the health authority.

PMID- 9774300
TI  - Validity of advertising claims for multivitamin preparation Vitacor 20/90 on the
      internet.

PMID- 9774301
TI  - Theories in health care and research: theories of masculinity.

PMID- 9774302
TI  - Understanding controlled trials: what outcomes should be measured?

PMID- 9774303
TI  - Use of calcium channel blockers and risk of suicide. Independent studies are
      needed before causality is established.

PMID- 9774305
TI  - European medicines evaluation agency is ahead of national licensing authorities.

PMID- 9774304
TI  - Practicalities of warfare required service personnel to be vaccinated against
      anthrax.

PMID- 9774306
TI  - Identifying asthma and chronic obstructive pulmonary disease in patients with
      persistent cough. Why was no control group studied?

PMID- 9774307
TI  - NSAIDs need not usually be withheld after orthopaedic surgery.

PMID- 9774308
TI  - Cost effectiveness of community leg ulcer clinics. Study compared dressing
      techniques in selected group of patients.

PMID- 9774309
TI  - Terminology for early pregnancy loss must be changed.

PMID- 9774310
TI  - Medical and psychological effects of early discharge after surgery for breast
      cancer. Patients can be discharged on second postoperative morning.

PMID- 9774311
TI  - Outcome of low back pain in general practice. Evidence based practice can improve
      outcome.

PMID- 9774314
TI  - John bruce bittiner 

PMID- 9774312
TI  - Successful treatment of toenail mycosis with terbinafine and itraconazole gives
      long term benefits.

PMID- 9774313
TI  - Post-exposure prophylaxis against HIV infection is hard to supply for expatriate
      staff.

PMID- 9774315
TI  - Health department shows lack of understanding 

PMID- 9774316
TI  - The woman in the Surgeon's body 

PMID- 9774317
TI  - Regulating how We die: the ethical, medical and legal issues surrounding
      physician-assisted suicide 

PMID- 9774318
TI  - How science takes stock: the story of meta-analysis 

PMID- 9774319
TI  - Website of the week 

PMID- 9774320
TI  - The national research register 

PMID- 9774322
TI  - We won't forget you, bill 

PMID- 9774321
TI  - Virtual politics in the new NHS 

PMID- 9774323
TI  - Such things as values 

PMID- 9774325
TI  - Getting clinicians to use evidence from systematic reviews is difficult 

PMID- 9774326
TI  - Ethnicity is more important than social class in young people's use of health
      services 

PMID- 9774324
TI  - Testing for D-dimer is useful in diagnosing venous thrombosis 

PMID- 9774327
TI  - A third of women would prefer a female breast surgeon 

PMID- 9774328
TI  - Younger HIV positive men have higher risk of acquiring gonorrhoea 

PMID- 9774329
TI  - Nurses can safely manage half of out of hours calls in primary care 

PMID- 9774331
TI  - Identification of in vivo substrates of the yeast mitochondrial chaperonins
      reveals overlapping but non-identical requirement for hsp60 and hsp10.
AB  - The mechanism of chaperonin-assisted protein folding has been mostly analyzed in
      vitro using non-homologous substrate proteins. In order to understand the
      relative importance of hsp60 and hsp10 in the living cell, homologous substrate
      proteins need to be identified and analyzed. We have devised a novel screen to
      test the folding of a large variety of homologous substrates in the mitochondrial
      matrix in the absence or presence of functional hsp60 or hsp10. The identified
      substrates have an Mr of 15-90 kDa and fall into three groups: (i) proteins that
      require both hsp60 and hsp10 for correct folding; (ii) proteins that completely
      fail to fold after inactivation of hsp60 but are unaffected by the inactivation
      of hsp10; and (iii) newly imported hsp60 itself, which is more severely affected
      by inactivation of hsp10 than by inactivation of pre-existing hsp60. The majority
      of the identified substrates are group I proteins. For these, the lack of hsp60
      function has a more pronounced effect than inactivation of hsp10. We suggest that
      homologous substrate proteins have differential chaperonin requirements,
      indicating that hsp60 and hsp10 do not always act as a single functional unit in
      vivo.

PMID- 9774332
TI  - A misfolded protein conformation is not a sufficient condition for in vivo
      glucosylation by the UDP-Glc:glycoprotein glucosyltransferase.
AB  - A key element in the quality control of glycoprotein folding is the UDP
      Glc:glycoprotein glucosyltransferase (GT), which in cell-free assays exclusively
      glucosylates misfolded glycoproteins. In order to test if such a protein
      conformation is a sufficient condition for in vivo glucosylation of all N-linked
      oligosaccharides by GT, a Schizosaccharomyces pombe double mutant (gls2/alg6) was
      constructed. With this mutant, Man9GlcNAc2 is transferred to proteins and no
      removal of glucose units added by GT occurs as it lacks glucosidase II. The same
      proportion of glucosylated (Glc1Man9GlcNAc2) and unglucosylated (Man9GlcNAc2 and
      Man8GlcNAc2) endoplasmic reticulum (ER)-specific compounds was produced when
      cells were pre-incubated for 10, 20 or 30 min and further incubated with
      [14C]glucose for 10 min at 28 degrees C with or without 5 mM dithiothreitol
      (DTT), thus indicating not only that DTT did not affect protein glucosylation but
      also that no increased glucosylation of glycoproteins occurred in the presence of
      the drug. Monitoring Golgi-specific modifications of oligosaccharides after pulse
      chase experiments performed in the presence or absence of 5 mM DTT showed that
      exit of the bulk of glycoproteins synthesized from the ER and thence their proper
      folding had been prevented by the drug. Cells pulse-chase labeled at 37 degrees C
      in the absence of DTT also yielded glucosylated and unglucosylated protein-linked
      oligosaccharides without Golgi-specific modifications. It was concluded that a
      misfolded protein conformation is not a sufficient condition for in vivo
      glucosylation of all N-linked oligosaccharides by GT.

PMID- 9774330
TI  - KIF2beta, a new kinesin superfamily protein in non-neuronal cells, is associated
      with lysosomes and may be implicated in their centrifugal translocation.
AB  - Lysosomes concentrate juxtanuclearly in the region around the microtubule
      organizing center by interaction with microtubules. Different experimental and
      physiological conditions can induce these organelles to move to the cell
      periphery by a mechanism implying a plus-end-directed microtubule-motor protein
      (a kinesin-like motor). The responsible kinesin-superfamily protein, however, is
      unknown. We have identified a new mouse isoform of the kinesin superfamily,
      KIF2beta, an alternatively spliced isoform of the known, neuronal kinesin, KIF2.
      Developmental expression pattern and cell-type analysis in vivo and in vitro
      reveal that KIF2beta is abundant at early developmental stages of the hippocampus
      but is then downregulated in differentiated neuronal cells, and it is mainly or
      uniquely expressed in non-neuronal cells while KIF2 remains exclusively neuronal.
      Electron microscopy of mouse fibroblasts and immunofluorescence of KIF2beta
      transiently-transfected fibroblasts show KIF2 and KIF2beta primarily associated
      with lysosomes, and this association can be disrupted by detergent treatment. In
      KIF2beta-overexpressing cells, lysosomes (labeled with anti-lysosome-associated
      membrane protein-1) become abnormally large and peripherally located at some
      distance from their usual perinuclear positions. Overexpression of KIF2 or
      KIF2beta does not change the size or distribution of early, late and recycling
      endosomes nor does overexpression of different kinesin superfamily proteins
      result in changes in lysosome size or positioning. These results implicate
      KIF2beta as a motor responsible for the peripheral translocation of lysosomes.

PMID- 9774333
TI  - Voltage-generated torque drives the motor of the ATP synthase.
AB  - The mechanism by which ion-flux through the membrane-bound motor module (F0)
      induces rotational torque, driving the rotation of the gamma subunit, was probed
      with a Na+-translocating hybrid ATP synthase. The ATP-dependent occlusion of 1
      (22)Na+ per ATP synthase persisted after modification of the c subunit ring with
      dicyclohexylcarbodiimide (DCCD), when 22Na+ was added first and ATP second, but
      not if the order of addition was reversed. These results support the model of ATP
      driven rotation of the c subunit oligomer (rotor) versus subunit a (stator) that
      stops when either a 22Na+-loaded or a DCCD-modified rotor subunit reaches the Na+
      impermeable stator. The ATP synthase with a Na+-permeable stator catalyzed
      22Na+out/Na+in-exchange after reconstitution into proteoliposomes, which was not
      significantly affected by DCCD modification of the c subunit oligomer, but was
      abolished by the additional presence of ATP or by a membrane potential (DeltaPsi)
      of 90 mV. We propose that in the idling mode of the motor, Na+ ions are shuttled
      across the membrane by limited back and forth movements of the rotor against the
      stator. This motional flexibility is arrested if either ATP or DeltaPsi induces
      the switch from idling into a directed rotation. The Propionigenium modestum ATP
      synthase catalyzed ATP formation with DeltaPsi of 60-125 mV but not with
      DeltapNa+ of 195 mV. These results demonstrate that electric forces are essential
      for ATP synthesis and lead to a new concept of rotary-torque generation in the
      ATP synthase motor.

PMID- 9774334
TI  - Crystal structure of an angiogenesis inhibitor bound to the FGF receptor tyrosine
      kinase domain.
AB  - Angiogenesis, the sprouting of new blood vessels from pre-existing ones, is an
      essential physiological process in development, yet also plays a major role in
      the progression of human diseases such as diabetic retinopathy, atherosclerosis
      and cancer. The effects of the most potent angiogenic factors, vascular
      endothelial growth factor (VEGF), angiopoietin and fibroblast growth factor (FGF)
      are mediated through cell surface receptors that possess intrinsic protein
      tyrosine kinase activity. In this report, we describe a synthetic compound of the
      pyrido[2,3-d]pyrimidine class, designated PD 173074, that selectively inhibits
      the tyrosine kinase activities of the FGF and VEGF receptors. We show that
      systemic administration of PD 173074 in mice can effectively block angiogenesis
      induced by either FGF or VEGF with no apparent toxicity. To elucidate the
      determinants of selectivity, we have determined the crystal structure of PD
      173074 in complex with the tyrosine kinase domain of FGF receptor 1 at 2.5 A
      resolution. A high degree of surface complementarity between PD 173074 and the
      hydrophobic, ATP-binding pocket of FGF receptor 1 underlies the potency and
      selectivity of this inhibitor. PD 173074 is thus a promising candidate for a
      therapeutic angiogenesis inhibitor to be used in the treatment of cancer and
      other diseases whose progression is dependent upon new blood vessel formation.

PMID- 9774335
TI  - Extracellular signal-regulated activation of Rap1 fails to interfere in Ras
      effector signalling.
AB  - The small GTPase Rap1 has been implicated in both negative and positive control
      of Ras-mediated signalling events. We have investigated which extracellular
      signals can activate Rap1 and whether this activation leads to a modulation of
      Ras effector signalling, i.e. the activation of ERK and the small GTPase Ral. We
      found that Rap1 is rapidly activated following stimulation of a large variety of
      growth factor receptors. These receptors include receptor tyrosine kinases for
      platelet-derived growth factor (PDGF) and epithelial growth factor (EGF), and G
      protein-coupled receptors for lysophosphatidic acid (LPA), thrombin and
      endothelin. At least three distinct pathways may transduce a signal towards Rap1
      activation: increase in intracellular calcium, release of diacylglycerol and cAMP
      synthesis. Surprisingly, activation of endogenous Rap1 fails to affect Ras
      dependent ERK activation. In addition, we found that although overexpression of
      active Rap1 is able to activate the Ral pathway, activation of endogenous Rap1 in
      fibroblasts does not result in Ral activation. Rap1 also does not negatively
      influence Ras-mediated Ral activation. We conclude that activation of Rap1 is a
      common event upon growth factor treatment and that the physiological function of
      Rap1 is likely to be different from modulation of Ras effector signalling.

PMID- 9774336
TI  - Calcium regulation of Ndr protein kinase mediated by S100 calcium-binding
      proteins.
AB  - Ndr is a nuclear serine/threonine protein kinase that belongs to a subfamily of
      kinases identified as being critical for the regulation of cell division and cell
      morphology. The regulatory mechanisms that control Ndr activity have not been
      characterized previously. In this paper, we present evidence that Ndr is
      regulated by EF-hand calcium-binding proteins of the S100 family, in response to
      changes in the intracellular calcium concentration. In vitro, S100B binds
      directly to and activates Ndr in a Ca2+-dependent manner. Moreover, Ndr is
      recovered from cell lysates in anti-S100B immunoprecipitates. The region of Ndr
      responsible for interaction with Ca2+/S100B is a basic/hydrophobic motif within
      the N-terminal regulatory domain of Ndr, and activation of Ndr by Ca2+/S100B is
      inhibited by a synthetic peptide derived from this region. In cultured cells, Ndr
      is rapidly activated following treatment with Ca2+ ionophore, and this activation
      is dependent upon the identified Ca2+/S100B-binding domain. Finally, Ndr activity
      is inhibited by W-7 in melanoma cells overexpressing S100B, but is unaffected by
      W-7 in melanoma cells that lack S100B. These results suggest that Ndr is
      regulated at least in part by changes in the intracellular calcium concentration,
      through binding of S100 proteins to its N-terminal regulatory domain.

PMID- 9774337
TI  - Gelsolin and functionally similar actin-binding proteins are regulated by
      lysophosphatidic acid.
AB  - An extensive survey was carried out for compounds capable of regulating actin
      binding proteins in a manner similar to phosphatidylinositol 4,5 bisphosphate (PI
      4,5-P2). For this purpose we developed a sensitive assay involving release of
      radioactively phosphorylated actin from the fragminP-actin complex. We found that
      the structurally simplest lysophospholipid, lysophosphatidic acid (LPA),
      dissociated the complex between fragminP and actin, whereas other
      lysophospholipids or sphingosine-1-phosphate were inactive. Furthermore, LPA
      inhibited the F-actin severing activity of human gelsolin, purified from plasma
      or as recombinant protein, mouse adseverin and Physarum fragminP. Dissociation of
      actin-containing complexes by LPA analyzed by gelfiltration indicated that LPA is
      active as a monomer, in contrast to PI 4,5-P2. We further show that binding of
      LPA to these actin-regulatory proteins promotes their phosphorylation by pp60(c
      src). A PI 4,5-P2-binding peptide counteracted the effects mediated by LPA,
      suggesting that LPA binds to the same target region in these actin-binding
      proteins. When both LPA and PI 4,5-P2 were used in combination we found that LPA
      reduced the threshold concentration at which PI 4,5-P2 was active. Significantly,
      LPA promoted the release of gelsolin from barbed actin filaments in
      octylglucoside-permeabilized human platelets. These results suggest that
      lysophosphatidic acid could act as an intracellular modulator of actin-binding
      proteins. Our findings can also explain agonist-induced changes in the actin
      cytoskeleton that are not mediated by polyphosphoinositides.

PMID- 9774338
TI  - Pyk2 and Src-family protein-tyrosine kinases compensate for the loss of FAK in
      fibronectin-stimulated signaling events but Pyk2 does not fully function to
      enhance FAK- cell migration.
AB  - The focal adhesion kinase (FAK) protein-tyrosine kinase (PTK) links transmembrane
      integrin receptors to intracellular signaling pathways. We show that expression
      of the FAK-related PTK, Pyk2, is elevated in fibroblasts isolated from murine fak
      /- embryos (FAK-) compared with cells from fak+/+ embryos (FAK+). Pyk2 was
      localized to perinuclear regions in both FAK+ and FAK- cells. Pyk2 tyrosine
      phosphorylation was enhanced by fibronectin (FN) stimulation of FAK- but not FAK+
      cells. Increased Pyk2 tyrosine phosphorylation paralleled the time-course of Grb2
      binding to Shc and activation of ERK2 in FAK- cells. Pyk2 in vitro
      autophosphorylation activity was not enhanced by FN plating of FAK- cells.
      However, Pyk2 associated with active Src-family PTKs after FN but not poly-L
      lysine replating of the FAK- cells. Overexpression of both wild-type (WT) and
      kinase-inactive (Ala457), but not the autophosphorylation site mutant (Phe402)
      Pyk2, enhanced endogenous FN-stimulated c-Src in vitro kinase activity in FAK-
      cells, but only WT Pyk2 overexpression enhanced FN-stimulated activation of co
      transfected ERK2. Interestingly, Pyk2 overexpression only weakly augmented FAK-
      cell migration to FN whereas transient FAK expression promoted FAK- cell
      migration to FN efficiently compared with FAK+ cells. Significantly, repression
      of endogenous Src-family PTK activity by p50(csk) overexpression inhibited FN
      stimulated cell spreading, Pyk2 tyrosine phosphorylation, Grb2 binding to Shc,
      and ERK2 activation in the FAK- but not in FAK+ cells. These studies show that
      Pyk2 and Src-family PTKs combine to promote FN-stimulated signaling events to
      ERK2 in the absence of FAK, but that these signaling events are not sufficient to
      overcome the FAK- cell migration defects.

PMID- 9774339
TI  - Pathogenic poxviruses reveal viral strategies to exploit the ErbB signaling
      network.
AB  - Virulence of poxviruses, the causative agents of smallpox, depends on virus
      encoded growth factors related to the mammalian epidermal growth factor (EGF).
      Here we report that the growth factors of Shope fibroma virus, Myxoma virus and
      vaccinia virus (SFGF, MGF and VGF) display unique patterns of specificity to ErbB
      receptor tyrosine kinases; whereas SFGF is a broad-specificity ligand, VGF binds
      primarily to ErbB-1 homodimers, and the exclusive receptor for MGF is a
      heterodimer comprised of ErbB-2 and ErbB-3. In spite of 10- to 1000-fold lower
      binding affinity to their respective receptors, the viral ligands are
      mitogenically equivalent or even more potent than their mammalian counterparts.
      This remarkable enhancement of cell growth is due to attenuation of receptor
      degradation and ubiquitination, which leads to sustained signal transduction. Our
      results imply that signal potentiation and precise targeting to specific receptor
      combinations contribute to cell transformation at sites of poxvirus infection,
      and they underscore the importance of the often ignored low-affinity ligand
      receptor interactions.

PMID- 9774340
TI  - A novel site for ubiquitination: the N-terminal residue, and not internal lysines
      of MyoD, is essential for conjugation and degradation of the protein.
AB  - The ubiquitin proteolytic pathway is a major system for selective protein
      degradation in eukaryotic cells. One of the first steps in the degradation of a
      protein via this pathway involves selective modification of epsilon-NH2 groups of
      internal lysine residues by ubiquitination. To date, this amino group has been
      the only known target for ubiquitination. Here we report that the N-terminal
      residue of MyoD is sufficient and necessary for promotion of conjugation and
      subsequent degradation of the protein. Substitution of all lysine residues in the
      protein did not affect significantly its conjugation and degradation either in
      vivo or in vitro. In cells, degradation of the lysine-less protein is inhibited
      by the proteasome inhibitors MG132 and lactacystin. Inhibition is accompanied by
      accumulation of high molecular mass ubiquitinated forms of the modified MyoD. In
      striking contrast, wild-type MyoD, in which all the internal Lys residues have
      been retained but the N-terminus has been extended by fusion of a short peptide,
      is stable both in vivo and in vitro. In a cell-free system, ATP and multiple
      ubiquitination are essential for degradation of the lysine-less protein. Specific
      chemical modifications have yielded similar results. Selective blocking of the
      alpha-NH2 group of wild-type protein renders it stable, while modification of the
      internal Lys residues with preservation of the free N-terminal group left the
      protein susceptible to degradation. Our data suggest that conjugation of MyoD
      occurs via a novel modification involving attachment of ubiquitin to the N
      terminal residue. The polyubiquitin chain is then synthesized on an internal Lys
      residue of the linearly attached first ubiquitin moiety.

PMID- 9774341
TI  - DEDD, a novel death effector domain-containing protein, targeted to the
      nucleolus.
AB  - The CD95 signaling pathway comprises proteins that contain one or two death
      effector domains (DED), such as FADD/Mort1 or caspase-8. Here we describe a novel
      37 kDa protein, DEDD, that contains an N-terminal DED. DEDD is highly conserved
      between human and mouse (98. 7% identity) and is ubiquitously expressed.
      Overexpression of DEDD in 293T cells induced weak apoptosis, mainly through its
      DED by which it interacts with FADD and caspase-8. Endogenous DEDD was found in
      the cytoplasm and translocated into the nucleus upon stimulation of CD95.
      Immunocytological studies revealed that overexpressed DEDD directly translocated
      into the nucleus, where it co-localizes in the nucleolus with UBF, a basal factor
      required for RNA polymerase I transcription. Consistent with its nuclear
      localization, DEDD contains two nuclear localization signals and the C-terminal
      part shares sequence homology with histones. Recombinant DEDD binds to both DNA
      and reconstituted mononucleosomes and inhibits transcription in a reconstituted
      in vitro system. The results suggest that DEDD is a final target of a chain of
      events by which the CD95-induced apoptotic signal is transferred into the
      nucleolus to shut off cellular biosynthetic activities.

PMID- 9774343
TI  - Cooperative DNA-binding by Bicoid provides a mechanism for threshold-dependent
      gene activation in the Drosophila embryo.
AB  - The Bicoid morphogen directs pattern formation along the anterior-posterior (A-P)
      axis of the Drosophila embryo. Bicoid is distributed in a concentration gradient
      that decreases exponentially from the anterior pole, however, it transcribes
      target genes such as hunchback in a step-function-like pattern; the expression
      domain is uniform and has a sharply defined posterior boundary. A 'gradient
      affinity' model proposed to explain Bicoid action states that (i) cooperative
      gene activation by Bicoid generates the sharp on/off switch for target gene
      transcription and (ii) target genes with different affinities for Bicoid are
      expressed at different positions along the A-P axis. Using an in vivo yeast assay
      and in vitro methods, we show that Bicoid binds DNA with pairwise cooperativity;
      Bicoid bound to a strong site helps Bicoid bind to a weak site. These results
      support the first aspect of the model, providing a mechanism by which Bicoid
      generates sharp boundaries of gene expression. However, contrary to the second
      aspect of the model, we find no significant difference between the affinity of
      Bicoid for the anterior gene hunchback and the posterior gene knirps. We propose,
      instead, that the arrangement of Bicoids bound to the target gene presents a
      unique signature to the transcription machinery that, in combination with overall
      affinity, regulates the extent of gene transcription along the A-P axis.

PMID- 9774344
TI  - Novel mutants of NAB corepressors enhance activation by Egr transactivators.
AB  - The NGFI-A binding corepressors NAB1 and NAB2 interact with a conserved domain
      (R1 domain) within the Egr1/NGFI-A and Egr2/Krox20 transactivators, and repress
      the transcription of Egr target promoters. Using a novel adaptation of the yeast
      two-hybrid screen, we have identified several point mutations in NAB corepressors
      that interfere with their ability to bind to the Egr1 R1 domain. Surprisingly,
      NAB proteins bearing some of these mutations increased Egr1 activity
      dramatically. The mechanism underlying the unexpected behavior of these mutants
      was elucidated by the discovery that NAB conserved domain 1 (NCD1) not only binds
      to Egr proteins but also mediates multimerization of NAB molecules. The
      activating mutants exert a dominant negative effect on NAB repression by
      multimerizing with native NAB proteins and preventing binding of endogenous NAB
      proteins with Egr transactivators. To examine NAB repression of a native Egr
      target gene, we show that NAB2 represses Egr2/Krox20-mediated activation of the
      bFGF/FGF-2 promoter, and that repression is reversed by coexpression of dominant
      negative NAB2. Because of their specific ability to alleviate NAB repression of
      Egr target genes, the dominant negative NAB mutants will be useful in elucidating
      the mechanism and function of NAB corepressors.

PMID- 9774342
TI  - A novel function of adenovirus E1A is required to overcome growth arrest by the
      CDK2 inhibitor p27(Kip1).
AB  - We show here that the adenovirus E1A oncoprotein prevents growth arrest by the
      CDK2 inhibitor p27(Kip1) (p27) in rodent fibroblasts. However, E1A neither binds
      p27 nor prevents inhibition of CDK2 complexes in vivo. In contrast, the amount of
      free p27 available to inhibit cyclin E/CDK2 is increased in E1A-expressing cells,
      owing to reduced expression of cyclins D1 and D3. Moreover, E1A allows cell
      proliferation in the presence of supraphysiological p27 levels, while c-Myc,
      known to induce a cellular p27-inhibitory activity, is only effective against
      physiological p27 concentrations. E1A also bypasses G1 arrest by roscovitine, a
      chemical inhibitor of CDK2. Altogether, these findings imply that E1A can act
      downstream of p27 and CDK2. Retinoblastoma (pRb)-family proteins are known CDK
      substrates; as expected, association of E1A with these proteins (but not with
      p300/CBP) is required for E1A to prevent growth arrest by either p27 or the
      CDK4/6 inhibitor p16(INK4a). Bypassing CDK2 inhibition requires an additional
      function of E1A: the mutant E1A Delta26-35 does not overcome p27-induced arrest,
      while it binds pRb-family proteins, prevents p16-induced arrest, and alleviates
      pRb-mediated repression of E2F-1 transcriptional activity (although E1A Delta26
      35 fails to restore expression of E2F-regulated genes in p27-arrested cells). We
      propose that besides the pRb family, E1A targets specific effector(s) of CDK2 in
      G1-S control.

PMID- 9774345
TI  - Chromatin interaction mechanism of transcriptional control in vivo.
AB  - We have used a kinetic analysis to distinguish possible mechanisms of activation
      of transcription of the different genes in the human beta globin locus. Based on
      in situ studies at the single-cell level we have previously suggested a dynamic
      mechanism of single genes alternately interacting with the locus control region
      (LCR) to activate transcription. However, those steady-state experiments did not
      allow a direct measurement of the dynamics of the mechanism and the presence of
      loci with in situ primary transcript signals from two beta-like genes in cis has
      left open the possibility that multiple genes in the locus could initiate
      transcription simultaneously. Kinetic assays involving removal of a block to
      transcription elongation in conjunction with RNA FISH show that multiple beta
      gene primary transcript signals in cis represent a transition between alternating
      transcriptional periods of single genes, supporting a dynamic interaction
      mechanism.

PMID- 9774346
TI  - Nucleosome structure of the yeast CHA1 promoter: analysis of activation-dependent
      chromatin remodeling of an RNA-polymerase-II-transcribed gene in TBP and RNA pol
      II mutants defective in vivo in response to acidic activators.
AB  - The Saccharomyces cerevisiae CHA1 gene encodes the catabolic L-serine (L
      threonine) dehydratase. We have previously shown that the transcriptional
      activator protein Cha4p mediates serine/threonine induction of CHA1 expression.
      We used accessibility to micrococcal nuclease and DNase I to determine the in
      vivo chromatin structure of the CHA1 chromosomal locus, both in the non-induced
      state and upon induction. Upon activation, a precisely positioned nucleosome (nuc
      1) occluding the TATA box and the transcription start site is removed. A strain
      devoid of Cha4p showed no chromatin alteration under inducing conditions. Five
      yeast TBP mutants defective in different steps in activated transcription
      abolished CHA1 expression, but failed to affect induction-dependent chromatin
      rearrangement of the promoter region. Progressive truncations of the RNA
      polymerase II C-terminal domain caused a progressive reduction in CHA1
      transcription, but no difference in chromatin remodeling. Analysis of swi1, swi3,
      snf5 and snf6, as well as gcn5, ada2 and ada3 mutants, suggested that neither the
      SWI/SNF complex nor the ADA/GCN5 complex is involved in efficient activation
      and/or remodeling of the CHA1 promoter. Interestingly, in a sir4 deletion strain,
      repression of CHA1 is partly lost and activator-independent remodeling of nuc-1
      is observed. We propose a model for CHA1 activation based on promoter remodeling
      through interactions of Cha4p with chromatin components other than basal factors
      and associated proteins.

PMID- 9774347
TI  - c-jun N-terminal kinase is involved in AUUUA-mediated interleukin-3 mRNA turnover
      in mast cells.
AB  - Whereas signalling pathways involved in transcriptional control have been studied
      extensively, the pathways regulating mRNA turnover remain poorly understood. We
      are interested in the role of mRNA stability in cell activation and oncogenesis
      using PB-3c mast cells as a model system. In these cells the short-lived
      interleukin-3 (IL-3) mRNA is stabilized by ionomycin treatment and following
      oncogenesis. To identify the signalling pathways involved in these mechanisms, we
      analysed the effect of different kinase inhibitors. SB202190 and wortmannin were
      shown to antagonize ionomycin-induced IL-3 mRNA stabilization in PB-3c cells in
      the presence of actinomycin D, and this effect coincided with their ability to
      inhibit c-jun N-terminal kinase (JNK) activation by ionomycin. Moreover,
      transfection of activated MEKK1 amplified ionomycin-induced IL-3 mRNA expression
      at the post-transcriptional level, and a dominant-negative mutant of JNK
      counteracted mRNA stabilization by ionomycin. Taken together, these data indicate
      that JNK is involved in the regulation of IL-3 mRNA turnover in mast cells. In
      addition, transfection experiments revealed that the cis-acting AU-rich element
      in the 3' untranslated region of IL-3 mRNA is necessary and sufficient to confer
      JNK-dependent mRNA stabilization in response to cell activation.

PMID- 9774348
TI  - Analysis of the functional specificity of RS domains in vivo.
AB  - A number of splicing factors contain extensive regions that are rich in arginine
      and serine (RS domains). These domains are thought to facilitate protein-protein
      interactions that are critical in the regulation of alternative splicing. Using a
      domain swap strategy, we have tested the ability of RS domains from several
      proteins to substitute in vivo for an essential RS domain in the Drosophila
      splicing regulator TRA-2. By several criteria, RS domains were found to vary
      significantly in their ability to support the splicing regulation functions of
      TRA-2. The RS domain of dU2AF50 functioned efficiently, while that of the dSRp55
      protein did not. Moreover, we find similar differences in the ability of RS
      domains to direct fusion proteins to discrete subnuclear sites at which TRA-2
      associates with spermatocyte chromosomes. These results indicate that RS domains
      are not all functionally equivalent in vivo.

PMID- 9774350
TI  - The Escherichia coli OxyS regulatory RNA represses fhlA translation by blocking
      ribosome binding.
AB  - OxyS is a small untranslated RNA which is induced in response to oxidative stress
      in Escherichia coli. This novel RNA acts as a global regulator to activate or
      repress the expression of as many as 40 genes, including the fhlA-encoded
      transcriptional activator and the rpoS-encoded sigma(s) subunit of RNA
      polymerase. Deletion analysis of OxyS showed that different domains of the small
      RNA are required for the regulation of fhlA and rpoS. We examined the mechanism
      of OxyS repression of fhlA and found that the OxyS RNA inhibits fhlA translation
      by pairing with a short sequence overlapping the Shine-Dalgarno sequence, thereby
      blocking ribosome binding/translation.

PMID- 9774349
TI  - The OxyS regulatory RNA represses rpoS translation and binds the Hfq (HF-I)
      protein.
AB  - The OxyS regulatory RNA integrates the adaptive response to hydrogen peroxide
      with other cellular stress responses and protects against DNA damage. Among the
      OxyS targets is the rpoS-encoded sigma(s) subunit of RNA polymerase. Sigma(s) is
      a central regulator of genes induced by osmotic stress, starvation and entry into
      stationary phase. We examined the mechanism whereby OxyS represses rpoS
      expression and found that the OxyS RNA inhibits translation of the rpoS message.
      This repression is dependent on the hfq-encoded RNA-binding protein (also denoted
      host factor I, HF-I). Co-immunoprecipitation and gel mobility shift experiments
      revealed that the OxyS RNA binds Hfq, suggesting that OxyS represses rpoS
      translation by altering Hfq activity.

PMID- 9774351
TI  - Probing the structure of complex macromolecular interactions by homolog
      specificity scanning: the P1 and P7 plasmid partition systems.
AB  - The P1 plasmid partition locus, P1 par, actively distributes plasmid copies to
      Escherichia coli daughter cells. It encodes two DNA sites and two proteins, ParA
      and ParB. Plasmid P7 uses a similar system, but the key macromolecular
      interactions are species specific. Homolog specificity scanning (HSS) exploits
      such specificities to map critical contact points between component
      macromolecules. The ParA protein contacts the par operon operator for operon
      autoregulation, and the ParB contacts the parS partition site during partition.
      Here, we refine the mapping of these contacts and extend the use of HSS to map
      protein-protein contacts. We found that ParB participates in autoregulation at
      the operator site by making a specific contact with ParA. Similarly, ParA acts in
      partition by making a specific contact with ParB bound at parS. Both these
      interactions involve contacts between a C-terminal region of ParA and the extreme
      N-terminus of ParB. As a single type of ParA-ParB complex appears to be involved
      in recognizing both DNA sites, the operator and the parS sites may both be
      occupied by a single protein complex during partition. The general HSS strategy
      may aid in solving the three-dimensional structures of large complexes of
      macromolecules.

PMID- 9774354
TI  - James conway 1921 1998 

PMID- 9774352
TI  - Capture of genomic and T-DNA sequences during double-strand break repair in
      somatic plant cells.
AB  - To analyze genomic changes resulting from double-strand break (DSB) repair,
      transgenic tobacco plants were obtained that carried in their genome a
      restriction site of the rare cutting endonuclease I-SceI within a negative
      selectable marker gene. After induction of DSB repair via Agrobacterium-mediated
      transient expression of I-SceI, plant cells were selected that carried a loss-of
      function phenotype of the marker. Surprisingly, in addition to deletions, in a
      number of cases repair was associated with the insertion of unique and repetitive
      genomic sequences into the break. Thus, DSB repair offers a mechanism for
      spreading different kinds of sequences into new chromosomal positions. This may
      have evolutionary consequences particularly for plants, as genomic alterations
      occurring in meristem cells can be transferred to the next generation. Moreover,
      transfer DNA (T-DNA), carrying the open reading frame of I-SceI, was found in
      several cases to be integrated into the transgenic I-SceI site. This indicates
      that DSB repair also represents a pathway for the integration of T-DNA into the
      plant genome.

PMID- 9774355
TI  - Isolation of a chromosome 1 region that contributes to high blood pressure and
      salt sensitivity.
AB  - Linkage analyses in the spontaneously hypertensive rat (SHR) suggest that a gene
      involved in blood pressure regulation may be located on rat chromosome 1, in the
      Sa region. To confirm this possibility, we replaced a region of chromosome 1 in
      the Wistar-Kyoto rat (WKY) defined by the markers D1Mit3 and MTPA with the
      corresponding chromosome segment from SHR. Genotyping using 65 polymorphic
      microsatellite markers throughout the entire genome confirmed the congenic status
      of this new strain designated WKY. SHR-D1Mit3/Rat57. In male WKY.SHR
      D1Mit3/Rat57, mean blood pressures in the daytime and in the nighttime assessed
      by radiotelemetry were significantly higher than those in male progenitor WKY.
      Moreover, salt loading significantly increased the mean blood pressure in male
      WKY.SHR-D1Mit3/Rat57 but not in male progenitor WKY. The present study confirmed
      the existence of a gene that contributes to high blood pressure and salt
      sensitivity in this chromosomal segment. This congenic strain represents a new
      animal model for fine mapping and characterization of the gene in this region
      involved in salt-sensitive hypertension.

PMID- 9774353
TI  - Polymerization of bacteriophage phi 29 replication protein p1 into protofilament
      sheets.
AB  - Protein p1 (85 amino acids) of the Bacillus subtilis phage phi29 is a membrane
      associated protein required for in vivo viral DNA replication. In the present
      study, we have constructed two fusion proteins, maltose-binding protein (MalE)-p1
      and MalE-p1DeltaN33. By using both sedimentation assays and negative-stain
      electron microscopy analysis, we demonstrated that MalE-p1 molecules self
      associated into long filamentous structures, which did not assemble further into
      larger arrays. These structures were constituted by a core of protein p1
      surrounded by MalE subunits. After removal of the MalE component by cleavage with
      protease factor Xa, the resulting protein p1 filaments tended to associate,
      forming bundles. The MalE-p1DeltaN33 fusion protein, however, did not self
      interact in solution. Nevertheless, after being separated from the MalE domain by
      factor Xa digestion, protein p1DeltaN33 assembled into long protofilaments that
      associated in a highly ordered, parallel array forming large two-dimensional
      sheets. These structures resemble eukaryotic tubulin and bacterial FtsZ polymers.
      In addition, we show that protein p1 influences the rate of in vivo phi29 DNA
      synthesis in a temperature-dependent manner. We propose that protein p1 is a
      component of a viral-encoded structure that associates with the bacterial
      membrane. This structure would provide an anchoring site for the viral DNA
      replication machinery.

PMID- 9774356
TI  - Successful isolation of a rat chromosome 1 blood pressure quantitative trait
      locus in reciprocal congenic strains.
AB  - Linkage analyses in experimental crosses of hypertensive and normotensive rats
      have strongly suggested the presence of a quantitative trait locus (QTL)
      influencing blood pressure on rat chromosome 1, at or near the Sa gene. To
      confirm the presence of such a locus and move toward identification of the
      causative gene, we have developed, through targeted breeding over 10 generations
      using an Sa gene polymorphism to select breeders at each generation, 2 congenic
      strains, 1 containing a segment of spontaneously hypertensive rat (SHR)
      chromosome 1 in a Wistar-Kyoto rat (WKY) genetic background (WKY.SHR-Sa), and the
      other a segment of WKY chromosome 1 in an SHR background (SHR.WKY-Sa). WKY.SHR-Sa
      contains at least approximately 26 cM of SHR chromosome 1, between markers
      mD7mit206 and D1Mit2 (and including the SHR allele of the Sa gene), and SHR.WKY
      Sa carries at least approximately 15 cM of WKY chromosome 1, between mD7mit206
      and D1Wox34 (and including the WKY allele of the Sa gene). Blood pressure of
      WKY.SHR-Sa rats measured at 16, 20, and 25 weeks of age was significantly higher
      than that of WKY, whereas blood pressure of SHR.WKY-Sa rats was significantly
      lower than that of SHR. At 25 weeks, the mean differences in systolic and
      diastolic blood pressure between WKY.SHR-Sa and WKY were +11.5 mm Hg (P=0.001)
      and +11.6 mm Hg mm Hg (P<0.001), respectively. The corresponding differences
      between SHR.WKy-Sa and SHR were -11.3 mm Hg (P=0.002) and -9.1 mm Hg (P=0.005),
      respectively. The differences represent about one fifth of the blood pressure
      difference between SHR and WKY. Renal Sa mRNA levels in the congenic strains
      reflected their Sa allele with a high level in WKY. SHR-Sa and a low level in
      SHR.WKY-Sa, consistent with previous data suggesting that the level of Sa
      expression is primarily determined by cis-acting elements in or near the Sa gene.
      Our results show that we have successfully isolated a major rat chromosome 1
      blood pressure QTL located in the vicinity of the Sa gene in reciprocal congenic
      strains derived from SHR and WKY. The strains can now be used to further define
      the region containing the QTL and also to characterize intermediary mechanisms
      through which the QTL influences blood pressure. In addition, comparison of the
      regions introgressed in our congenic strains with the location of the peak LOD
      score for chromosome 1 blood pressure QTL in second filial generation progeny
      derived from our SHRxWKY cross suggests that there may be at least 1 further QTL
      influencing blood pressure on this rat chromosome.

PMID- 9774357
TI  - The Sa gene: what does it mean?

PMID- 9774358
TI  - Salt-sensitive hypertension induced by sensory denervation: introduction of a new
      model.
AB  - To test the novel hypothesis that neonatal degeneration of capsaicin-sensitive
      sensory nerves causes the rat to respond to a salt load with a significant and
      sustained rise in blood pressure, newborn Wistar rats were given 50 mg/kg
      capsaicin subcutaneously on the 1st and 2nd day of life. Control rats were
      treated with vehicle. Immediately after the weanling period, male rats were
      divided into 4 groups and fed different sodium diets for 2 weeks: capsaicin
      pretreatment plus high sodium diet (4%, CAP-HS), capsaicin plus normal sodium
      diet (0.5%, CAP-NS), control plus high sodium diet (CON-HS), and control plus
      normal sodium diet (CON-NS). Both tail-cuff systolic blood pressure and mean
      arterial pressure with anesthesia were significantly higher in CAP-HS than in CAP
      NS, CON-HS, and CON-NS (P<0.05), but they were not different among the latter 3
      groups. Radioimmunoassay revealed that levels of calcitonin gene related peptide
      in dorsal root ganglia were markedly decreased by capsaicin treatment (P<0.05).
      Twenty-four-hour urine volume and urine sodium excretion were significantly lower
      in CAP-HS than in CON-HS but were higher in CAP-HS and CON-HS compared with CAP
      NS and CON-NS (P<0.05). Urine potassium excretion was not different among the 4
      groups. Thus, this study provides the first evidence that neonatal degeneration
      of capsaicin-sensitive sensory nerves renders the rat salt-sensitive in terms of
      blood pressure regulation. Furthermore, our data suggest that neonatal capsaicin
      treatment may impair renal sodium and water excretion responses to high sodium
      intake. This model will provide a novel experimental paradigm for exploring
      underlying molecular mechanisms linked with salt-sensitive hypertension and
      sensory nerve function.

PMID- 9774359
TI  - Structural vascular changes in hypertension: role of angiotensin II, dietary
      sodium supplementation, blood pressure, and time.
AB  - The dose and time dependence of angiotensin II (Ang II) induced hypertension and
      structural vascular changes and the effect of dietary sodium supplementation on
      these relationships were investigated. Male Sprague-Dawley rats were treated with
      50, 100, or 200 ng . kg-1 . min-1 Ang II subcutaneously for 4 or 12 weeks on
      normal sodium diet (0.7% NaCl) or with 50 ng . kg-1 . min-1 Ang II SC for 12
      weeks on high sodium diet (2% NaCl). Additional rats were sham-operated and fed
      normal sodium (control rats) or high sodium diet. Plasma Ang II level of rats
      receiving 100 ng . kg-1 . min-1 Ang II for 4 weeks was 26+/-5 pg/mL (mean+/-SEM,
      n=7) compared with 11+/-2 pg/mL (n=15) in control rats (P<0.03). Lumen and
      external diameters of small (50 to 100 microm OD) and intermediate-size (100 to
      150 microm OD) resistance arteries were measured in maximally dilated, pump
      perfused (55 to 60 mm Hg), in situ fixed mesenteric vascular beds of rats, and
      wall-to-lumen ratios (W/L) were calculated. Large mesenteric arteries of rats
      treated with 100 ng . kg-1 . min-1 Ang II for 12 weeks were examined to
      distinguish hypertrophy from hyperplasia of vascular muscle. Tail systolic blood
      pressure (BP) and W/L of resistance arteries of Ang II treated rats increased in
      a dose-dependent manner. Treatment with 50 ng . kg-1 . min-1 Ang II for 12 weeks
      had no significant effect on BP but produced the same increase in W/L (+10%, n=8,
      P<0.06) as 100 ng . kg-1 . min-1 Ang II for 4 weeks (+9%, n=18, P<0.05) (time
      dependence). A 2% NaCl diet for 12 weeks had no significant effect on either BP
      or W/L, but in combination with 50 ng . kg-1 . min-1 Ang II, it increased
      systolic BP by 31 mm Hg (P<0.01) and W/L of small resistance arteries by 28%
      (P<0.01) (synergism). In rats treated with 100 ng . kg-1 . min-1 Ang II for 12
      weeks, arterial smooth muscle cell thickness was increased without a change in
      the number of cell layers (hypertrophy). There was a dissociation between the
      average BP load (the area under the weekly systolic BP curve) of Ang II treated
      rats and the W/L of their mesenteric resistance arteries. Ang II induced
      hypertension and structural vascular changes are dose- and time-dependent and
      synergistically enhanced by dietary sodium supplementation. Dissociation between
      BP and vascular structure in Ang II treated rats suggests that a direct trophic
      effect of Ang II may contribute to the development of structural vascular
      changes.

PMID- 9774360
TI  - Regulation of mitogen-activated protein kinase phosphatase-1 in vascular smooth
      muscle cells.
AB  - Mitogen-activated protein (MAP) kinase cascades are major signaling systems by
      which cells transduce extracellular cues into intracellular responses. In
      general, MAP kinases are activated by phosphorylation on tyrosine and threonine
      residues and inactivated by dephosphorylation. Therefore, MAP kinase phosphatase
      1 (MKP-1), a dual-specificity protein tyrosine phosphatase that exhibits
      catalytic activity toward both regulatory sites on MAP kinases, is suggested to
      be responsible for the downregulation of extracellular signal-regulated kinase
      (ERK), stress-activated protein kinase (SAPK), and p38 MAP kinase. In the present
      study, we examined the role of these MAP kinases in the induction of MKP-1 in
      vascular smooth muscle cells (VSMCs). Extracellular stimuli such as platelet
      derived growth factor (PDGF), 12-O-tetradecanoylphorbol 13-acetate (TPA), and
      angiotensin II, which activated ERK but not SAPK/p38 MAP kinase, induced a
      transient induction of MKP-1 mRNA and its intracellular protein. In addition, PD
      098059, an antagonist of MEK (MAP kinase/ERK kinase), the upstream kinase of ERK,
      significantly reduced the PDGF-induced activation of ERK and potently inhibited
      the expression of MKP-1 after stimulation with PDGF, thereby demonstrating the
      induction of MKP-1 in response to activation of the ERK signaling cascade.
      Furthermore, anisomycin, a potent stimulus of SAPK and p38 MAP kinase, also
      induced MKP-1 mRNA expression. This effect of anisomycin was significantly
      inhibited in the presence of the p38 MAP kinase antagonist SB 203580. These data
      suggest the induction of MKP-1, not only after stimulation of the cell growth
      promoting ERK pathway but also in response to activation of stress-responsive MAP
      kinase signaling cascades. We suggest that this pattern of MKP-1 induction may be
      a negative feedback mechanism in the control of MAP kinase activity in VSMCs.

PMID- 9774361
TI  - Role of calcium-sensitive tyrosine kinase Pyk2/CAKbeta/RAFTK in angiotensin II
      induced Ras/ERK signaling.
AB  - In cardiac fibroblasts, angiotensin II (Ang II) induced a rapid increase in
      extracellular signal regulated kinase (ERK) activity in a pertussis toxin
      insensitive manner. This ERK activation was abolished by the Gq-associated
      phospholipase C inhibitor U73122 but was insensitive to protein kinase C (PKC)
      inhibitors or PKC downregulation by phorbol ester. Intracellular Ca2+ chelation
      by BAPTA-AM or TMB-8 abolished Ang II induced ERK activation, whereas treatment
      with EGTA or nifedipine did not affect it. Ca2+ ionophore A23187 also induced a
      rapid increase in ERK activity to an extent similar to that of Ang II
      stimulation. Calmodulin inhibitors (W7 and calmidazolium) and tyrosine kinase
      inhibitors (genistein and ST638) completely blocked ERK activation by Ang II and
      A23187. Both Ang II and A23187 caused a rapid increase in the binding of GTP to
      p21(Ras), which was nearly abolished by genistein and calmidazolium. Transfection
      with the dominant negative mutant of Ras and the Ras inhibitor manumycin
      completely inhibited Ang II induced ERK activation. It was also found for the
      first time that cardiac fibroblasts abundantly expressed Ca2+-sensitive tyrosine
      kinase Pyk2/CAKbeta/RAFTK and that Ang II markedly induced its activation in a
      Ca2+/calmodulin-sensitive manner. Overexpression of the dominant negative mutant
      of Pyk2 significantly attenuated Ang II or A23187-induced ERK activities (36% and
      38% inhibition compared with that in mock-transfected cells, respectively) and
      ERK tyrosine phosphorylation levels, as well as an increase in the binding of GTP
      to p21(Ras). These findings demonstrate that in cardiac fibroblasts, Ang II
      induced Ras/ERK activation is dominantly regulated by Gq-coupled Ca2+/calmodulin
      signaling and that Pyk2 plays an important role in the signal transmission for
      efficient activation of the Ang II induced Ras/ERK pathway.

PMID- 9774362
TI  - Positive association of tyrosine hydroxylase microsatellite marker to essential
      hypertension.
AB  - Despite advances in the understanding of monogenic hypertensive disorders, the
      genetic contribution to essential hypertension has yet to be elucidated. The
      position of tyrosine hydroxylase (TH) as the rate-limiting enzyme in
      catecholamine biosynthesis renders it a candidate gene for the etiology of
      hypertension. The TH gene contains an internal, informative microsatellite marker
      (TCAT)9. We undertook (1) an association study in a group of well-characterized
      hypertensive subjects (HT) and control subjects (NT) and (2) an affected sibling
      pair (ASP) study using sibships from our local family practices. Two hundred
      twenty-seven hypertensive patients (pretreatment systolic/diastolic blood
      pressure [BP] range, 139/94 to 237/133 mm Hg; age range [SD], 30 to 71 [8.5]
      years) were age- and gender-matched with 206 control subjects (BP range, 96/62 to
      153/86 mm Hg; age range, 40 to 70 [7.6] years). One hundred thirty-six affected
      sibling pairs were recruited for our linkage study; 73 young borderline
      hypertensive subjects (YHT) (pretreatment BP range, 123/76 to 197/107 mm Hg; age
      range, 20 to 51 [9.4] years) were also recruited in whom recent pretreatment
      norepinephrine and epinephrine levels were available. All subjects were white.
      The TH short tandem repeat (STR) was amplified using specific polymerase chain
      reaction cycling conditions in all subjects, and products were run on an ABI 373A
      sequencer. TH alleles were assigned using Genescan and Genotyper software. Five
      TH alleles were present and designated A through E. Allele frequencies in the NT
      population (A, B, C, D, and E: 0.24, 0.17, 0.13, 0.20, and 0.26, respectively)
      were significantly different from the HT cohort (A, B, C, D, and E: 0.24, 0.19,
      0.11, 0.11, and 0.35, respectively), P<0. 0005 (Pearson's test chi2=19.94; 4 df).
      The E allele appears overrepresented in the HT group, whereas the D allele
      appears to be overrepresented in the NT group. TH genotype frequencies were also
      significantly different between cases and controls (P<0.001; chi2=36. 57; 14 df).
      Both groups were in Hardy-Weinberg proportion. There was a trend (NS) for the D
      allele to be associated with a lower BP when BP was analyzed as a quantitative
      trait. ASP linkage data was analyzed using Splink, a nonparametric program.
      Expected values for sharing 0, 1, and 2 alleles (Z0, Z1, and Z2, respectively)
      may be expected to be 25%, 50%, and 25%, respectively, by chance (assuming
      identity by descent). These probabilities were calculated by Splink as 34, 68,
      and 34, respectively, and compared with observed values of 36.8, 67.9, and 31.3,
      respectively; thus, there was no excess sharing of TH alleles among affected
      sibling pairs (P=0.59; logarithm of odds ratio score, 0.0). TH allele frequencies
      in our YHT group (A, B, C, D, and E: 0.24, 0.20, 0.12, 0.15, and 0.29,
      respectively) were similar to those of our NT cohort (P>0.05). There was a trend
      for lower pretreatment plasma norepinephrine levels with the D allele in this YHT
      cohort. A common and potentially functional variant at codon 81(Val-->Met) within
      exon 2 of the TH gene (which we show to be in linkage disequilibrium with TH-STR)
      was also typed in our YHT but did not associate with catecholamine levels and is
      therefore unlikely to account for our findings with D and E TH-STR. In
      conclusion, the TH locus strongly associates with essential hypertension in a
      case-control model using well-characterized hypertensive and control groups. An
      ASP linkage model was negative, presumably because of lack of power. This study
      suggests that the TH gene, or a nearby gene, may be involved in the etiology of
      essential hypertension.

PMID- 9774363
TI  - Human spiral artery renin-angiotensin system.
AB  - Pregnancy induces uterine spiral arteries to remodel into dilated uteroplacental
      vessels by an unknown mechanism called "physiological change." In women who
      develop preeclampsia, however, many spiral arteries remain unchanged or develop
      medial hyperplasia and atherosis. We recently demonstrated that angiotensinogen
      is expressed by remodeling spiral arteries in first-trimester decidua. We
      hypothesize that a local spiral artery renin-angiotensin system mediates
      pregnancy-induced remodeling of these vessels. In this study we tested for
      expression of renin, angiotensin-converting enzyme, and angiotensin II type 1
      receptor genes in the first-trimester uterus using reverse-transcription
      polymerase chain reaction. Expression was localized by in situ hybridization and
      immunohistochemistry. Renin, angiotensin-converting enzyme, and the angiotensin
      II type 1 receptor are all expressed in and around remodeling spiral arteries.
      These observations suggest that a local spiral artery renin-angiotensin system
      may play a role in pregnancy-induced remodeling of these vessels. Elevated
      angiotensinogen expression in women homozygous for the A(-6) variant in the
      angiotensinogen promoter may promote abnormal remodeling, whereas relatively
      lower levels in women homozygous for G(-6) may permit enough normal remodeling to
      protect these women from preeclampsia.

PMID- 9774364
TI  - G protein beta3 subunit gene variant and blood pressure variation in Canadian Oji
      Cree.
AB  - The subunits of the heterotrimeric G proteins are attractive candidate gene
      products for both susceptibility to essential hypertension and interindividual
      variation in blood pressure. There is alternative splicing of exon 9 of the gene
      encoding the beta3 subunit of heterotrimeric G proteins (GNB3) associated with a
      C-->T change at nucleotide 825, which activates a cryptic splice site. The 825T
      allele results in a gene product that is 41 amino acids smaller than the wild
      type gene product. G protein heterotrimers containing the shorter variant are
      more reactive than those containing the wild type, and the 825T allele appears to
      be associated with essential hypertension. To evaluate whether this variant is
      associated with hypertension or blood pressure in other human samples, we
      genotyped 447 young adult Oji-Cree for the GNB3 C825T variation. We found that
      the frequency of the GNB3 825T allele was 0.501 in the Oji-Cree, which is
      considerably higher than the frequency observed in whites. Furthermore, genetic
      variation of the GNB3 nucleotide 825 was significantly associated with variation
      in systolic pressure but not diastolic pressure. Specifically, subjects with the
      825T/T genotype had significantly lower systolic pressure than subjects with the
      825C/T and 825C/C genotypes; the association was independent of sex. Furthermore,
      the 825T allele frequency tended to be higher in subjects who took
      antihypertensive medications than in subjects who did not (0.571 versus 0.496;
      P=NS), although this young sample had relatively few subjects with hypertension.
      The findings support an association of variation in this gene with variation in
      blood pressure.

PMID- 9774365
TI  - Intralipid enhances alpha1-adrenergic receptor mediated pressor sensitivity.
AB  - The dyslipidemia in obese hypertensive persons may contribute to their increased
      vascular alpha-adrenergic receptor reactivity and tone. To further examine this
      notion, we conducted 2 studies of pressor sensitivity to phenylephrine, an alpha1
      adrenergic receptor agonist, in lean normotensive subjects. In the first study
      (n=6), pressor responses to phenylephrine were obtained before and during a
      saline and heparin infusion. On another day, pressor reactivity to phenylephrine
      was measured before and during infusion of 20% Intralipid at 0.5 mL . m-2 . min-1
      with heparin at 1000 U/h to increase lipoprotein lipase activity and raise
      nonesterified fatty acids (NEFAs). In the second study (n=8), baseline reactivity
      to phenylephrine was obtained on 2 separate days and repeated after raising NEFAs
      and triglycerides either with 0.8 mL . m-2 . min-1 of 20% Intralipid alone or
      together with heparin. The infusion of saline and heparin did not significantly
      change plasma NEFAs from baseline (516+/-90 versus 512+/-108 micromol/L,
      respectively; P=NS) or the dose of phenylephrine required to raise mean blood
      pressure by 20 mm Hg ([PD20PE]; 1.00+/-0.14 versus 0. 95+/-0.10 microg . kg-1 .
      min-1, respectively, P=NS). Intralipid at 0.5 mL . m-2 . min-1 with heparin
      raised plasma NEFAs to 793+/-30 micromol/L per liter (P<0.05 versus baseline) and
      reduced PD20PE from 1.01+/-0.10 to 0.80+/-0.09 microg . kg-1 . min-1 (P<0.05).
      Compared with baseline, Intralipid alone increased plasma NEFAs to 946+/-80
      micromol/L (P<0.05), and NEFAs increased further with the addition of heparin to
      2990+/-254 micromol/L (P<0.01). Despite an apparently greater increase of plasma
      NEFAs with Intralipid and heparin, Intralipid alone and together with heparin
      similarly reduced PD20PE. Across all study conditions, changes in levels of
      triglycerides and NEFAs correlated with changes in mean arterial pressure
      responses to phenylephrine, especially at the 0.4- microg . kg-1 . min-1 infusion
      rate of phenylephrine (r=0.64, P<0.01 and r=0. 54, P<0.01, respectively). These
      data suggest that raising levels of plasma NEFAs and/or triglycerides enhances
      alpha1-adrenoceptor mediated pressor sensitivity. The findings suggest that lipid
      abnormalities in obese hypertensives, which include elevated NEFAs and
      triglycerides, contribute to greater vascular alpha1-adrenergic reactivity.

PMID- 9774367
TI  - Nerve growth factor gene locus explains elevated renal nerve growth factor mRNA
      in young spontaneously hypertensive rats.
AB  - Nerve growth factor (NGF) controls the growth of sympathetic nerves and is
      increased in young spontaneously hypertensive rats (SHR). The NGF gene has been
      linked genetically with hypertension in the SHR strain and may explain high NGF
      mRNA levels. To test for genetic linkage between the NGF gene and its expression
      in vivo, we examined renal NGF mRNA levels in male SHR, control Donryu rats
      (DRY), and F2 rats derived from SHR and DRY at ages 2, 4, 10, and 20 weeks. Tail
      cuff blood pressure was measured at 4, 10, and 20 weeks of age. NGF mRNA levels
      in SHR (NGF genotype: SS) were higher than those in DRY (NGF genotype: DD) at 2,
      4, and 10 weeks of age (P<0.0001) but the same at 20 weeks of age. In the F2
      generation, the S allele was associated with significantly (P=0.01) higher renal
      NGF mRNA levels at 2 weeks of age. Mean NGF mRNA levels fell (P=0.01) with age in
      F2 rats, and the difference between SS and DD genotype F2 rats diminished at
      older ages and was not significant. In F2 rats there was a positive correlation
      between the number of NGF S alleles inherited and tail-cuff pressure (P<0.007).
      Our findings indicate that the NGF locus is an important regulator of NGF mRNA
      levels. It is likely that mutations in or near the NGF gene explain in part high
      early NGF gene expression in SHR.

PMID- 9774366
TI  - Raised cerebrovascular resistance in idiopathic orthostatic intolerance: evidence
      for sympathetic vasoconstriction.
AB  - Patients with idiopathic orthostatic intolerance (IOI) exhibit symptoms
      suggestive of cerebral hypoperfusion and an excessive decrease in cerebral blood
      flow associated with standing despite sustained systemic blood pressure. In 9
      patients (8 women and 1 man aged 22 to 48 years) with IOI, we tested the
      hypothesis that volume loading (2000 cc normal saline) and alpha-adrenoreceptor
      agonism improve systemic hemodynamics and cerebral perfusion and that the
      decrease in cerebral blood flow with head-up tilt (HUT) could be attenuated by
      alpha-adrenoreceptor blockade with phentolamine. At 5 minutes of HUT, volume
      loading (-20+/-3.2 bpm) and phenylephrine (-18+/-3.4 bpm) significantly reduced
      upright heart rate compared with placebo; the effect was diminished at the end of
      HUT. Phentolamine substantially increased upright heart rate at 5 minutes (20+/
      3.7 bpm) and at the end of HUT (14+/-5 bpm). With placebo, mean cerebral blood
      flow velocity decreased by 33+/-6% at the end of HUT. This decrease in cerebral
      blood flow with HUT was attenuated by all 3 interventions. We conclude that in
      patients with IOI, HUT causes a substantial decrease in cerebrovascular blood
      flow velocity. The decrease in blood flow velocity with HUT can be attenuated
      with interventions that improve systemic hemodynamics and therefore decrease
      reflex sympathetic activation. Moreover, alpha-adrenoreceptor blockade also
      blunts the decrease in cerebral blood flow with HUT but at the price of
      deteriorated systemic hemodynamics. These observations may suggest that in
      patients with IOI, excessive sympathetic activity contributes to the paradoxical
      decrease in cerebral blood flow with upright posture.

PMID- 9774369
TI  - Calcium channel blockade enhances nitric oxide synthase expression by cultured
      endothelial cells.
AB  - In a recent study, we found marked increases in nitric oxide (NO) production and
      endothelial and inducible NO synthase (eNOS and iNOS) expressions with calcium
      channel blockade in rats with chronic renal failure. This study was undertaken to
      determine whether enhanced NO production with calcium channel blockade is a
      direct effect of this therapy or a consequence of the associated hemodynamic and
      humoral changes. We tested the effects of a calcium channel blocker, felodipine
      (10(-5), 10(-6), and 10(-7) mol/L), on nitrate and nitrite (NOx) generation, Ca2+
      dependent and -independent NOS activity, and eNOS and iNOS protein masses in
      proliferating and quiescent rat aortic endothelial cells in culture. Compared
      with vehicle alone, felodipine significantly increased NOx generation, Ca2+
      dependent NOS activity, and eNOS protein mass in proliferating and quiescent
      endothelial cells. Felodipine did not modify the stimulatory action of 10% fetal
      calf serum on DNA synthesis (thymidine incorporation) and cell proliferation.
      Ca2+-independent NOS activity and iNOS protein expression were negligible and
      unaffected by calcium channel blockade. NOx production and NOS expression were
      greater in proliferating cells than in quiescent cells. Thus, calcium channel
      blockade upregulates endothelial NO production in vitro, confirming our previous
      in vivo study. This observation indicates that the reductions in cytosolic [Ca2+]
      and vasodilation with calcium channel blockade are not only due to inhibition of
      Ca2+ entry but also to an NO-cGMP mediated mechanism.

PMID- 9774368
TI  - Effects of dietary fish and weight reduction on ambulatory blood pressure in
      overweight hypertensives.
AB  - Obesity is a major factor contributing to hypertension and increased risk of
      cardiovascular disease. Regular consumption of dietary fish and omega3 fatty
      acids of marine origin can lower blood pressure (BP) levels and reduce
      cardiovascular risk. This study examined the potential effects of combining
      dietary fish rich in omega3 fatty acids with a weight loss regimen in overweight
      hypertensive subjects, with ambulatory BP levels as the primary end point. Using
      a factorial design, 69 overweight medication-treated hypertensives were
      randomized to a daily fish meal (3.65 g omega3 fatty acids), weight reduction,
      the 2 regimens combined, or a control regimen for 16 weeks. Sixty-three subjects
      with a mean+/-SEM body mass index of 31.6+/-0.5 kg/m2 completed the study. Weight
      fell by 5.6+/-0.8 kg with energy restriction. Dietary fish and weight loss had
      significant independent and additive effects on 24-hour ambulatory BP. Effects
      were greatest on awake systolic and diastolic BP (P<0.01); relative to control,
      awake pressures fell 6.0/3.0 mm Hg with dietary fish alone, 5.5/2.2 mm Hg with
      weight reduction alone, and 13.0/9.3 mm Hg with fish and weight loss combined.
      These results also remained significant after further adjustment for changes in
      urinary sodium, potassium, or the sodium/potassium ratio, as well as dietary
      macronutrients. Dietary fish also significantly reduced 24-hour (-3.1+/-1.4 bpm,
      P=0.036) and awake (-4.2+/-1.6 bpm, P=0. 013) ambulatory heart rates. Weight
      reduction had a significant effect on sleeping heart rate only (-3.2+/-1.7 bpm,
      P=0.037). Combining a daily fish meal with a weight-reducing regimen led to
      additive effects on ambulatory BP and decreased heart rate. The effects were
      large, suggesting that cardiovascular risk and antihypertensive drug requirements
      are likely to be reduced substantially by combining dietary fish meals rich in
      omega3 fatty acids with weight-loss regimens in overweight medication-treated
      hypertensives. The reduction in heart rate seen with dietary fish suggests a
      cardiac/autonomic component, as well as vascular effects, of increased
      consumption of omega3 fatty acid from fish.

PMID- 9774370
TI  - Nitric oxide metabolism in erythropoietin-induced hypertension: effect of calcium
      channel blockade.
AB  - Long-term administration of erythropoietin (EPO) frequently causes hypertension
      in humans and animals with chronic renal failure (CRF). We recently demonstrated
      that EPO-induced hypertension is hematocrit independent and accompanied by
      elevated cytosolic [Ca2+]i and nitric oxide (NO) resistance. This study was
      undertaken to examine the effects of therapy with EPO alone or together with
      calcium channel blockade on NO metabolism. Urinary excretion of NO metabolites
      (NOx) and thoracic aorta and kidney endothelial and inducible NO synthases (eNOS
      and iNOS) were studied in 4 groups of 6 nephrectomized rats treated with either
      placebo, EPO, the calcium channel blocker felodipine, or EPO plus felodipine for
      6 weeks. A group of sham-operated placebo-treated animals served as control. The
      placebo-treated CRF group exhibited moderate hypertension, elevated basal and
      depressed stimulated platelet [Ca2+]i, reduced urinary NOx excretion, and
      diminished vascular and renal eNOS and iNOS proteins. EPO therapy further raised
      blood pressure and increased resting and stimulated [Ca2+]i but did not change
      NOx excretion or NOS proteins. Concurrent administration of felodipine abrogated
      EPO-induced hypertension, normalized resting and stimulated [Ca2+]i, and
      increased NOx excretion and eNOS and iNOS proteins. Thus, EPO therapy leads to
      marked increases in blood pressure and resting and stimulated [Ca2+]i. These
      abnormalities are ameliorated by calcium channel blockade, which restores [Ca2+]i
      to normal and increases vascular and renal NOS expression.

PMID- 9774371
TI  - Evidence for a difference in nitric oxide biosynthesis between healthy women and
      men.
AB  - There is indirect evidence for a gender difference in nitric oxide (NO) synthesis
      from vascular endothelium. The aim of the present study was to determine NO
      production more directly in healthy women and men by the measurement of 15N
      nitrate excreted in urine after the intravenous administration of L-[15N]2
      guanidino arginine. Twenty-four healthy volunteers (13 men aged 22 to 40 years
      and 11 women aged 23 to 42 years) participated in this study. No subjects were
      receiving any medication. Women were studied between the 7th and 14th days of
      their menstrual cycles. Arterial blood pressure was measured oscillometrically,
      and 1.13 micromol L-[15N]2 arginine was administered intravenously after an
      overnight fast. Urine was collected for the next 36 hours in separate 12-hour
      periods. Urinary 15N/14N nitrate ratio was assessed by dry combustion in an
      isotope ratio mass spectrometer. Mean 36-hour urinary 15N nitrate excretion was
      greater in women than in men (2111+/-139 versus 1682+/-87 etamol; P<0.05).
      Furthermore, total urinary 15N nitrate excretion was associated inversely with
      the mean arterial blood pressure in the whole group of subjects (coefficient of
      correlation, 0.47; P=0.022). The present data show that whole-body production of
      NO is greater in healthy premenopausal women than in men under ambulatory
      conditions. The cellular origin of NO measured in this study is unknown, but
      differences in endothelial production could underlie differences in vascular
      function between men and women.

PMID- 9774372
TI  - Nitric oxide dependent vasodilation in young spontaneously hypertensive rats.
AB  - Conflicting evidence exists on the possible impairment of tonic nitric oxide (NO)
      mediated vasodilation as a causative factor in the genesis of human as well as
      experimental hypertension. We evaluated the tonic NO-dependent vasodilation from
      the pressor response to NO synthesis inhibition by NG-monomethyl-L-arginine (L
      NMMA) in 9 conscious, chronically instrumented spontaneously hypertensive rats
      (SHR) at 12 weeks of age, ie, during the early established hypertensive stage.
      Nine age-matched Wistar-Kyoto rats (WKY) were used as controls. The pressor
      responses to L-NMMA (100 mg . kg-1 IV bolus plus 1.5 mg . kg-1 . min-1 infusion
      for 60 minutes) as well as to non NO-dependent pressor stimuli, namely,
      vasopressin (2, 4, and 8 ng . kg-1) and phenylephrine (0.5, 1, and 2 microg . kg
      1) given as IV boluses, were assessed both under control conditions and during
      suppression of autonomic reflexes by hexamethonium (30 mg . kg-1 IV bolus+1.5 mg
      . kg-1 . min-1 infusion). Rather than being reduced, the pressor responses to L
      NMMA were 39% and 71% larger in the control and areflexic conditions,
      respectively, than those observed in WKY (both P<0.01). A similar pattern was
      observed for the pressor responses to vasopressin (+37% and +68% in the control
      and areflexic conditions, respectively; both P<0.01) and phenylephrine, (+20% and
      +52%; both P<0.05). Additional groups of 6-week-old prehypertensive SHR (n=11)
      and age-matched WKY (n=11) were subjected to an identical protocol: in these
      animals, the pressor responses to L-NMMA were similar in each strain, as were the
      pressor responses to vasopressin and phenylephrine in both control and areflexic
      conditions. In conclusion, our observations indicate that during the
      developmental phase of hypertension in the SHR model, namely, during the
      prehypertensive as well as the early established hypertensive stage, NO-dependent
      vasodilation is preserved (if not enhanced) so that a putative impairment of this
      function provides no significant pathogenic contribution to the onset of
      hypertension in this experimental model.

PMID- 9774373
TI  - Vasodilator response to systemic but not to local hyperinsulinemia in the human
      forearm.
AB  - Insulin-mediated vasodilation has been proposed as an important determinant of
      whole-body insulin-stimulated glucose disposal. However, it is not clear whether
      the vasodilator effect of insulin results from a direct action of the hormone or
      whether alternative mechanisms are involved. To better characterize the mechanism
      of insulin-mediated vasorelaxation, we compared forearm blood flow (FBF)
      responses to local (intra-arterial) and systemic (intravenous, euglycemic clamp)
      hyperinsulinemia in 10 healthy lean subjects using venous occlusion
      plethysmography. In addition, we assessed the effect of nitric oxide (NO)
      synthase inhibition by NG-monomethyl-L-arginine (L-NMMA) on the vasodilator and
      metabolic responses to hyperinsulinemia. Similar forearm concentrations of
      insulin were achieved during local and systemic infusion (231+/-39 versus 265+/
      22 microU/mL; P=0.54). Of note, FBF did not change significantly in response to
      local hyperinsulinemia (from 2.6+/-0.3 to 2.4+/-0.3 mL . min-1 . dL-1; P=0.50).
      In contrast, systemic hyperinsulinemia caused a 52% increase in FBF (from 2.5+/
      0.2 to 3. 8+/-0.5 mL . min-1 . dL-1; P<0.004), which was reversed by L-NMMA (FBF
      decreased from 3.8+/-0.5 to 2.3+/-0.2 mL . min-1 . dL-1; P=0. 004). We conclude
      that systemic, but not local, hyperinsulinemia induces vasodilation in the
      forearm. Our findings suggest that insulin-mediated vasodilation is not due
      solely to a direct stimulatory effect of insulin but involves additional
      mechanisms activated only during systemic hyperinsulinemia.

PMID- 9774374
TI  - Effects of eprosartan on renal function and cardiac hypertrophy in rats with
      experimental heart failure.
AB  - Activation of the renin-angiotensin system may contribute to the derangement in
      renal and cardiac function in congestive heart failure. The present study
      evaluated the effects of eprosartan, a selective angiotensin II receptor
      antagonist, on renal hemodynamic and excretory parameters and on the development
      of cardiac hypertrophy in rats with aortocaval fistula, an experimental model of
      congestive heart failure. Infusion of eprosartan (1.0 mg/kg) in rats with
      aortocaval fistula produced a significant increase (+34%) in total renal blood
      flow and a sustained decrease (-33%) in the calculated renal vascular resistance.
      These effects on renal hemodynamics were more pronounced than those observed in
      sham-operated control rats and occurred despite a significant fall (-12%) in mean
      arterial blood pressure. Moreover, eprosartan caused a preferential increase in
      renal cortical blood perfusion and significantly increased glomerular filtration
      in rats with congestive heart failure. Chronic administration of eprosartan (5.0
      mg/kg per day for 7 days through osmotic minipumps inserted intraperitoneally on
      the day of operation) resulted in a significant enhancement of urinary sodium
      excretion compared with nontreated rats with heart failure. Moreover,
      administration of eprosartan to salt-retaining rats with congestive heart failure
      resulted in a progressive increase and ultimate recovery in urinary sodium
      excretion. Finally, early treatment with eprosartan blocked the development of
      cardiac hypertrophy in rats with aortocaval fistula to a larger extent than the
      angiotensin-converting enzyme inhibitor enalapril. These findings emphasize the
      importance of angiotensin II in mediating the impairment in renal function and
      induction of cardiac hypertrophy in heart failure and further suggest that
      angiotensin II receptor blockade may be a useful treatment of these consequences
      in severe cardiac failure.

PMID- 9774375
TI  - Maladaptive remodeling of cardiac myocyte shape begins long before failure in
      hypertension.
AB  - Progression to failure in hypertension is associated with ventricular dilation,
      excessive myocyte lengthening, and an increase in myocyte length/width ratio. The
      temporal development of these changes in relation to impaired pump performance is
      unknown. We examined isolated myocytes from 1- to 12-month-old spontaneously
      hypertensive heart failure (SHHF) rats who develop heart failure at approximately
      24 months of age. Left ventricular myocyte cross-sectional area reached a maximum
      of approximately 350 to 400 microm2 at 3 months of age and did not change
      significantly thereafter. Nonetheless, LV systolic wall stress, a known stimulus
      for myocyte transverse growth, increased progressively between 3 and 12 months of
      age. Unlike the situation in normally aging rats with stable body mass, myocyte
      length in SHHF rats continued to increase with aging (P<0.05 from 9 to 12 months
      of age). In summary, (1) left ventricular myocyte transverse growth reaches an
      upper limit by 3 months of age although systolic wall stress continues to rise;
      and (2) cell length is significantly increased by 12 months of age. This study
      suggests that maladaptive remodeling of cardiac myocyte shape begins long before
      pump failure in hypertension. Additionally, it appears that the left ventricle
      may be robbed of an important adaptive mechanism to normalize wall stress (eg,
      myocyte transverse growth) early in the progression to failure.

PMID- 9774376
TI  - Adrenomedullin, a new vasoactive peptide, is increased in preeclampsia.
AB  - Adrenomedullin is a novel peptide that elicits a long-lasting vasorelaxant
      activity. Recently, we found high concentrations of adrenomedullin in maternal
      and umbilical cord plasma and in amniotic fluid in full-term human pregnancy,
      indicating a role of this peptide during gestation. To investigate the
      possibility that adrenomedullin is involved in the pathophysiology of
      preeclampsia, we measured its concentration in maternal and fetoplacental
      compartments. We studied 12 normotensive nonpregnant women, 13 hypertensive
      nonpregnant subjects, 29 patients with preeclampsia, and 30 normotensive pregnant
      women. In all patients, plasma was collected from the cubital vein, and amniotic
      fluid samples were obtained by transabdominal amniocentesis or at elective
      cesarean section. Plasma samples from umbilical vein and placental tissues were
      collected at delivery. Adrenomedullin was assayed on plasma and amniotic fluid
      samples using a specific radioimmunoassay, and its localization and distribution
      on placental sections was determined by immunohistochemistry. Adrenomedullin
      concentrations were higher in hypertensive than in normotensive nonpregnant
      patients. Pregnant women had higher adrenomedullin levels than nonpregnant
      subjects, although maternal plasma adrenomedullin concentrations did not differ
      between normal pregnant and preeclamptic women. Preeclamptic patients showed
      higher concentrations (P<0.01) than normotensive pregnant women of adrenomedullin
      in amniotic fluid (252+/-29 versus 112+/-10 fmol/ micromol creatinine) and
      umbilical vein plasma (18.1+/-2.1 versus 8. 5+/-1.1 fmol/mL). Increased local
      production of adrenomedullin is associated with preeclampsia. The fetus seems to
      be responsible for the higher levels of this hormone. Increased adrenomedullin
      concentrations may be necessary to maintain placental vascular resistance and/or
      fetal circulation at a physiological level.

PMID- 9774377
TI  - Early cardiac changes after menopause.
AB  - The mechanisms underlying the increased cardiovascular risk after menopause are
      incompletely known. To investigate whether menopause may induce left ventricular
      structural and functional adaptations in normotensive and hypertensive women, we
      compared in a case-control setting (1) 76 untreated hypertensive premenopausal
      women with 76 postmenopausal women and (2) 30 normotensive premenopausal women
      with 30 postmenopausal women. Subjects were individually matched by age (+/-5
      years; range, 45 to 55), clinic systolic blood pressure (+/-5 mm Hg), and body
      mass index (+/-2 kgxm-2). All subjects underwent 24-hour blood pressure
      monitoring and M-mode echocardiography. Age, clinic and daytime blood pressure,
      body mass index, and smoking habits did not differ between the paired groups.
      After menopause, blood pressure fall from day to night was lower in both
      normotensives (10/15% versus 16/21%) and hypertensives (12/17% versus 16/21%)
      (all P<0.01). Menopause was also associated with a greater left ventricular
      relative wall thickness (38.8% versus 35.1% in normotensives, 40.2% versus 37.5%
      in hypertensives) and a reduced midwall fractional shortening (17.3% versus 18.6%
      in normotensives, 16.6% versus 17.9% in hypertensives) (all P<0.05). We conclude
      that menopause is associated with blunted day-night blood pressure reduction,
      impaired left ventricular systolic performance, and concentric left ventricular
      geometric pattern. These finding are independent of presence or absence of high
      blood pressure.

PMID- 9774378
TI  - Effect of vasopressin antagonism on structure and mechanics of small arteries and
      vascular expression of endothelin-1 in deoxycorticosterone acetate salt
      hypertensive rats.
AB  - The structural and mechanical properties of small arteries are altered in rat
      models of hypertension. The precise role of humoral factors in these changes has
      not been determined. In deoxycorticosterone acetate (DOCA) salt hypertension,
      endothelin-1 (ET-1) peptide content and gene expression are enhanced in
      mesenteric resistance arteries. These vessels also present augmented
      vasoconstrictor responsiveness to vasopressin versus control uninephrectomized
      rats. To determine whether an interaction exists between vasopressin and ET-1 in
      the pathogenesis of small-artery structural alterations in DOCA-salt rats, we
      examined the effect of chronic V1 vasopressin receptor antagonism (OPC-21268, 30
      mg/kg BID) on the structure and mechanical properties of mesenteric resistance
      arteries using a pressure myograph and the effect on preproendothelin-1 (preproET
      1) gene expression, determined by Northern blot analysis of preproET-1 mRNA. Tail
      cuff systolic pressures were elevated in DOCA-salt (200+/-11 mm Hg) versus
      uninephrectomized rats (109+/-4 mm Hg) and decreased slightly but significantly
      by OPC-21268 to 187+/-7 mm Hg (P<0.01). Treatment with DOCA-salt increased
      vascular media-lumen ratios and media cross-sectional areas and reduced both
      stress and incremental elastic modulus for a given pressure. However, there was
      no change in distensibility or incremental elastic modulus versus media stress.
      OPC-21268 partially attenuated the vascular growth in DOCA-salt rats. PreproET-1
      mRNA was increased 2-fold in mesenteric arteries of DOCA-salt rats versus
      uninephrectomized rats, an effect abrogated by OPC-21268. Thus, DOCA-salt
      hypertension is associated with altered morphology of the small-arterial wall,
      without altering stiffness of the arterial wall components. OPC-21268 regressed
      in part these changes, suggesting the involvement of vasopressin. The concomitant
      attenuation of enhanced ET-1 expression by OPC-21268 suggests that ET-1 may be
      involved in mediating in part the vascular effects of vasopressin in DOCA-salt
      hypertensive rats.

PMID- 9774381
TI  - RNA polymerase II holoenzymes and subcomplexes.

PMID- 9774379
TI  - Dual inhibition of neutral endopeptidase and angiotensin-converting enzyme in
      rats with hypertension and diabetes mellitus.
AB  - It has been suggested that combined inhibition of angiotensin-converting enzyme
      (ACE) and neutral endopeptidase (NEP) may lower blood pressure more effectively
      than either treatment alone, independent of the degree of salt and volume status
      or the activity of the renin-angiotensin system. The effects of NEP inhibition in
      hypertension associated with diabetes mellitus are largely unknown. We therefore
      compared ACE inhibition, NEP inhibition, and dual NEP/ACE inhibition in diabetic
      hypertensive rats. Spontaneously hypertensive rats (SHR) aged 9 to 10 weeks were
      injected with either streptozotocin (45 mg/kg) or citrate buffer and randomized
      to receive either the ACE inhibitor captopril (25 mg/kg BID), the NEP inhibitor
      SCH 42495 (30 mg/kg BID), the dual NEP/ACE inhibitor S 21402 (25 or 50 mg/kg
      BID), or vehicle by gavage for 4 weeks. A group of diabetic SHR was also
      allocated to receive the combination of SCH 42495 (30 mg/kg BID) and captopril
      (25 mg/kg BID). The degree of renal NEP inhibition was determined by
      autoradiography, and plasma renin activity (PRA) was determined by
      radioimmunoassay. In diabetic SHR, the dual NEP/ACE inhibitor (50 mg/kg BID), as
      well as the combination of the NEP inhibitor and the ACE inhibitor, reduced
      systolic blood pressure more effectively than the ACE inhibitor (P<0.001) or the
      NEP inhibitor (P<0.001) alone. In nondiabetic SHR, the dual NEP/ACE inhibitor and
      the ACE inhibitor were equally effective, while the NEP inhibitor had only slight
      blood pressure lowering effects. Relative heart weight decreased in parallel to
      the changes in blood pressure. Renal NEP was clearly inhibited (70% to 92%;
      P<0.001) by both the NEP inhibitor and the dual NEP/ACE inhibitor. Both the ACE
      inhibitor and the dual NEP/ACE inhibitor increased PRA, but the stimulating
      effect of dual NEP/ACE inhibition on PRA was less than that observed with ACE
      inhibition alone (P<0.05). Albuminuria in diabetic SHR was lower during treatment
      with both the dual NEP/ACE inhibitor (50 mg/kg BID) and the combination of NEP
      inhibition and ACE inhibition compared with vehicle treatment (P<0.05). In
      conclusion, the present study shows that hypertension in SHR with streptozotocin
      induced diabetes is modulated by natriuretic peptides and thus is sensitive to
      NEP inhibition. The increased efficacy of dual NEP/ACE inhibition on blood
      pressure in diabetic SHR, compared with ACE or NEP inhibition alone, suggests
      that this therapeutic approach may prove beneficial in the treatment of
      hypertension associated with diabetes mellitus and other forms of volume
      dependent hypertension.

PMID- 9774382
TI  - Oncoprotein TLS interacts with serine-arginine proteins involved in RNA splicing.
AB  - The gene encoding the human TLS protein, also termed FUS, is located at the site
      of chromosomal translocations in human leukemias and sarcomas where it forms a
      chimeric fusion gene with one of several different genes. To identify interacting
      partners of TLS, we screened a yeast two-hybrid cDNA library constructed from
      mouse hematopoietic cells using the C-terminal region of TLS in the bait plasmid.
      Two cDNAs encoding members of the serine-arginine (SR) family of proteins were
      isolated. The first SR protein is the mouse homolog of human splicing factor
      SC35, and the second SR member is a novel 183-amino acid protein that we term
      TASR (TLS-associated serine-arginine protein). cDNA cloning of human TASR
      indicated that mouse and human TASR have identical amino acid sequences. The
      interactions between TLS and these two SR proteins were confirmed by co
      transfection and immunoprecipitation studies. In vivo splicing assays indicated
      that SC35 and TASR influence splice site selection of adenovirus E1A pre-mRNA.
      TLS may recruit SR splicing factors to specific target genes through interaction
      with its C-terminal region, and chromosomal translocations that truncate the C
      terminal region of TLS may prevent this interaction. Thus TLS translocations may
      alter RNA processing and play a role in malignant transformation.

PMID- 9774384
TI  - Functional association of platelet endothelial cell adhesion molecule-1 and
      phosphoinositide 3-kinase in human neutrophils.
AB  - In this paper we show that the engagement of the platelet-endothelial cell
      adhesion molecule-1 (PECAM-1/CD31) up-regulates the adhesion of human neutrophils
      to the EA.hy926 endothelial cell line through a phosphoinositide 3-kinase (PI3K)
      dependent pathway. Indeed, LY294002 and wortmannin prevented the effect of PECAM
      1/CD31 cross-linking on cell adhesion, at concentrations known to inhibit PI3K
      without affecting other kinases. Both compounds blocked neutrophil binding to
      murine fibroblasts transfected with human ICAM-1, to purified ICAM-1 protein, or
      to fibronectin, suggesting that PECAM-1/CD31-mediated up-regulation of beta2 and
      beta1 integrin-mediated adhesion is PI3K-sensitive. We also provide evidence for
      the association of PECAM-1/CD31 to PI3K, because PI3K was detectable in
      neutrophil lysates after PECAM-1/CD31 cross-linking and immunoprecipitation.
      PECAM-1/CD31-dependent recruitment of PI3K was suggested by the finding that the
      serine/threonine kinase p70 S6 kinase (S6K), a signaling protein downstream of
      PI3K, is activated in neutrophils upon PECAM-1/CD31 cross-linking, based on the
      appearance of serine phosphorylation in S6K immunoprecipitates. In turn, S6K is
      not directly involved in the up-regulation of integrin function because
      rapamycin, which can inhibit S6K independent of PI3K, did not block PECAM-1/CD31
      induced adhesion of neutrophils to beta1 and beta2 integrin substrates. In
      conclusion, PECAM-1/CD31 appears to be one of the molecules functionally coupled
      to PI3K, suggesting that this enzyme may represent a common pathway of integrin
      and adhesiveness regulation in leukocytes.

PMID- 9774383
TI  - Evidence that tumor necrosis factor alpha converting enzyme is involved in
      regulated alpha-secretase cleavage of the Alzheimer amyloid protein precursor.
AB  - The amyloid protein, Abeta, which accumulates in the brains of Alzheimer
      patients, is derived by proteolysis of the amyloid protein precursor (APP). APP
      can undergo endoproteolytic processing at three sites, one at the amino terminus
      of the Abeta domain (beta-cleavage), one within the Abeta domain (alpha
      cleavage), and one at the carboxyl terminus of the Abeta domain (gamma-cleavage).
      The enzymes responsible for these activities have not been unambiguously
      identified. By the use of gene disruption (knockout), we now demonstrate that
      TACE (tumor necrosis factor alpha converting enzyme), a member of the ADAM family
      (a disintegrin and metalloprotease-family) of proteases, plays a central role in
      regulated alpha-cleavage of APP. Our data suggest that TACE may be the alpha
      secretase responsible for the majority of regulated alpha-cleavage in cultured
      cells. Furthermore, we show that inhibiting this enzyme affects both APP
      secretion and Abeta formation in cultured cells.

PMID- 9774385
TI  - ATP1AL1, a member of the non-gastric H,K-ATPase family, functions as a sodium
      pump.
AB  - The human ATP1AL1-encoded protein (an alpha subunit of the human non-gastric H,K
      ATPase) has previously been shown to assemble with the gastric H,K-ATPase beta
      subunit (gH,Kbeta) to form a functionally active ionic pump in HEK 293 cells.
      This pump has been found to be sensitive to both SCH 28080 and ouabain. However,
      the 86Rb+-influx mediated by the ATP1AL1-gH,Kbeta heterodimer in HEK 293 cells is
      at least 1 order of magnitude larger than the maximum ouabain-sensitive proton
      efflux detected in the same cells. In this study we find that the intracellular
      Na+ content in cells expressing ATP1AL1 and gH,Kbeta is two times lower than that
      in control HEK 293 cells in response to incubation for 3 h in the presence of 1
      microM ouabain. Moreover, analysis of net Na+ efflux in HEK 293 expressing the
      ATP1AL1-gH,Kbeta heterodimer reveals the presence of Na+ extrusion activity that
      is not sensitive to 1 microM ouabain but can be inhibited by 1 mM of this drug.
      In contrast, ouabain-inhibitable Na+ efflux in control HEK 293 cells is similarly
      sensitive to either 1 microM or 1 mM ouabain. Finally, 86Rb+ influx through the
      ATP1AL1-gH,Kbeta complex is comparable to the 1 mM ouabain-sensitive Na+ efflux
      in the same cells. The data presented here suggest that the enzyme formed by
      ATP1AL1 and the gastric H,K-ATPase beta subunit in HEK 293 cells mediates
      primarily Na+,K+ rather than H+,K+ exchange.

PMID- 9774386
TI  - Mutation at the processing site of chicken low density lipoprotein receptor
      related protein impairs efficient endoplasmic reticulum exit, but proteolytic
      cleavage is not essential for its endocytic functions.
AB  - The low density lipoprotein receptor-related protein (LRP) is synthesized as a
      proreceptor that undergoes post-translational proteolytic processing, yielding a
      noncovalently associated alphabeta dimer as the mature LRP. We tested the role of
      processing by creating a mutant in which the P1 residue (Arg3942) of the
      consensus site for furin cleavage (Arg-Asn-Arg-Arg3942 downward arrow) was
      replaced with Ser in chicken LRP. Transfection of the mutant LRP (designated LRP
      RS) into a Chinese hamster ovary cell line lacking endogenous LRP resulted in
      expression of the unprocessed full-length proreceptor. Comparison of cell lines
      stably expressing either the wild-type LRP (LRP-wt) or the unprocessed LRP-RS
      showed that at comparable expression levels, both receptors restored the
      sensitivity of cellular protein synthesis to Pseudomonas exotoxin A (IC50 = 25
      ng/ml). Subcellular fractionation and neuraminidase treatment showed that both
      LRP forms were transported to the plasma membrane. In addition, LRP-RS exhibited
      kinetics of binding, endocytosis, and degradation of methylamine-activated alpha2
      macroglobulin that were identical to those of LRP-wt. The internalization rate
      constant was similar for LRP-wt (Ke = 0.259 min-1) and mutant LRP-RS (Ke = 0.252
      min-1), suggesting that it takes about 4 min for the entire surface LRP pool to
      be internalized. Sorting of LRP from the endosomal compartment to lysosomes or
      recycling to the plasma membrane were also unaltered in mutant LRP-RS. Pulse
      chase analysis showed that the lack of processing of LRP had no effect on the
      stability of its post-endoplasmic reticulum form or on the rate of its
      intracellular transit from the endoplasmic reticulum to the Golgi apparatus.
      However, the exit of mutant LRP from the endoplasmic reticulum was retarded by
      the Arg3942-to-Ser substitution, as evidenced by prolonged retention within the
      endoplasmic reticulum (t1/2 = 4 h for LRP-wt and t1/2 > 13 h for LRP-RS).

PMID- 9774387
TI  - An eukaryotic RuvB-like protein (RUVBL1) essential for growth.
AB  - A human protein (RUVBL1), consisting of 456 amino acids (50 kDa) and highly
      homologous to RuvB, was identified by using the 14-kDa subunit of replication
      protein A (hsRPA3) as bait in a yeast two-hybrid system. RuvB is a bacterial
      protein involved in genetic recombination that bears structural similarity to
      subunits of the RF-C clamp loader family of proteins. Fluorescence in situ
      hybridization analysis demonstrated that the RUVBL1 gene is located at 3q21, a
      region with frequent rearrangements in different types of leukemia and solid
      tumors. RUVBL1 co-immunoprecipitated with at least three other unidentified
      cellular proteins and was detected in the RNA polymerase II holoenzyme complex
      purified over multiple chromatographic steps. In addition, two yeast homologs,
      scRUVBL1 and scRUVBL2 with 70 and 42% identity to RUVBL1, respectively, were
      revealed by screening the complete Saccharomyces cerevisiae genome sequence.
      Yeast with a null mutation in scRUVBL1 was nonviable. Thus RUVBL1 is an
      eukaryotic member of the RuvB/clamp loader family of structurally related
      proteins from bacteria and eukaryotes that is essential for viability of yeast.

PMID- 9774388
TI  - RNA polymerase II elongation complexes containing the Cockayne syndrome group B
      protein interact with a molecular complex containing the transcription factor IIH
      components xeroderma pigmentosum B and p62.
AB  - Transcription factor IIH (TFIIH) is involved both in transcription initiation by
      RNA polymerase II and in nucleotide excision-repair. Nucleotide excision-repair
      occurs at higher rates in transcriptionally active regions of the genome. Genetic
      studies indicate that this transcription-coupled repair is dependent on the
      Cockayne syndrome group A and B proteins, as well as TFIIH subunits. Previous
      work indicated that Cockayne syndrome group B interacts with RNA polymerase II
      molecules engaged in ternary complexes containing DNA and RNA. Evidence presented
      here indicates that this complex can interact with a factor containing the TFIIH
      core subunits p62 and xeroderma pigmentosum subunit B/excision repair cross
      complementing 3. The targeting of TFIIH or a TFIIH-like repair factor to
      transcriptionally active DNA indicates a potential mechanism for transcription
      coupled repair in human cells.

PMID- 9774389
TI  - Platelet agonists enhance the import of phosphatidylethanolamine into human
      platelets.
AB  - It is unknown whether the endocytosis-independent transfer of phospholipids from
      lipoproteins to platelets is regulated by platelet agonists such as thrombin. The
      movements of the choline phospholipids phosphatidylcholine and sphingomyelin
      (labeled with either 14C or the fluorescent pyrenedecanoic acid) between low
      density lipoproteins and platelets were unaffected by thrombin (0.5 unit/ml). In
      contrast, thrombin accelerated the import of diacyl phosphatidylethanolamine (PE)
      and alkenylacyl phosphatidylethanolamine into platelets by about 4-fold.
      Similarly, thrombin receptor-activating peptide (15 microM), collagen (10
      microgram/ml), and ADP (10 microM) enhanced PE uptake. High density lipoprotein
      particles and egg phosphatidylcholine vesicles were also donors for stimulation
      of platelet PE import. Part of the [14C]arachidonic acid-labeled PE transferred
      from low density lipoprotein to platelets activated by thrombin and collagen was
      metabolized to 14C-eicosanoids. Inhibitors of protein kinase C partially
      prevented thrombin-induced [14C]PE uptake, while direct activators of protein
      kinase C increased incorporation of [14C]PE into platelets. Proteinaceous
      factor(s) recovered in the extracellular medium from ADP- and thrombin-activated
      platelet suspensions were found to accelerate the transfer of pyrenedecanoic acid
      labeled PE between donor and acceptor lipid vesicles. The stimulation of import
      of ethanolamine phospholipids led to a 2-fold enhancement of the prothrombinase
      activity of thrombin-activated platelets. Our study demonstrates that
      physiological platelet stimuli increase specifically the transfer of ethanolamine
      phospholipids from lipoproteins to platelets through a secretion-dependent
      mechanism. This might contribute to the increase of procoagulant activity of
      stimulated platelets.

PMID- 9774390
TI  - Internalization of the lymphocytic surface protein CD22 is controlled by a novel
      membrane proximal cytoplasmic motif.
AB  - CD22 is a key receptor on B-lymphocytes that modulates signaling during antigenic
      stimulation. We have defined a novel cytoplasmic motif in human CD22 that
      controls its unusually rapid turnover at the plasma membrane. Chimeric and
      mutated CD22alpha cDNA vectors were constructed and stably transfected in CD22
      negative Jurkat T-lymphocytic cells. Two assays were employed to measure
      CD22alpha internalization: first, cytoplasmic uptake of radioiodinated anti-CD22
      monoclonal antibody; and second, lethal targeting of a toxin, saporin, into cells
      via CD22 using bispecific F(ab')2 ([anti-CD22 x anti-saporin]) antibody. Results
      showed that CD22alpha lacking a cytoplasmic tail was not internalized and that
      replacement of the cytoplasmic tail of CD19 with that of CD22alpha resulted in a
      chimeric molecule that behaved like CD22alpha and internalized rapidly. Step-wise
      deletion of the cytoplasmic tail of CD22alpha located the internalization motif
      to a polar region of 11 residues (QRRWKRTQSQQ) proximal to the plasma membrane, a
      part of the molecule predicted to form a coil or turn structure. Interestingly,
      additional CD22 mutants showed that the two glutamine residues sandwiching the
      serine are critical to internalization but that the serine itself is not.

PMID- 9774392
TI  - Protein folding activity of Hsp70 is modified differentially by the hsp40 co
      chaperones Sis1 and Ydj1.
AB  - Specification of Hsp70 action in cellular protein metabolism may occur through
      the formation of specialized Hsp70:Hsp40 pairs. To test this model, we compared
      the ability of purified Sis1 and Ydj1 to regulate the ATPase and protein-folding
      activity of Hsp70 Ssa1 and Ssb1/2 proteins. Ydj1 and Sis1 could both functionally
      interact with Ssa1, but not the Ssb1/2 proteins, to refold luciferase.
      Interestingly, Ydj1:Ssa1 could promote up to four times more luciferase folding
      than Sis1:Ssa1. This functional difference was explored and could not be
      accounted for by differences in the ability of Sis1 and Ydj1 to regulate Ssa1
      ATPase activity. Instead, differences in the chaperone function of Ydj1 and Sis1
      were observed. Ydj1 was dramatically more effective than Sis1 at suppressing the
      thermally induced aggregation of luciferase. Paradoxically, Sis1 and Ydj1 could
      bind similar quantities of chemically denatured luciferase. The polypeptide
      binding domain of Sis1 was found to lie between residues 171-352 and correspond
      to its conserved carboxyl terminus. The conserved carboxyl terminus of Ydj1 is
      also known to participate in the binding of nonnative polypeptides. Thus, Ydj1
      appears more efficient at assisting Ssa1 in folding luciferase because its
      contains a zinc finger-like region that is absent from Sis1. Ydj1 and Sis1 are
      structurally and functionally distinct Hsp40 proteins that can specify Ssa1
      action by generating Hsp70:Hsp40 pairs that exhibit different chaperone
      activities.

PMID- 9774391
TI  - Regulation of apoptosis by alpha-subunits of G12 and G13 proteins via apoptosis
      signal-regulating kinase-1.
AB  - Many growth factors and G protein-coupled receptors activate mitogen-activated
      protein (MAP) kinase pathways. The MAP kinase pathways are involved in the
      regulation of the ubiquitous process of apoptosis or programmed cell death. Two
      related MAP kinase kinase kinases, apoptosis-signal regulating kinase 1 (ASK1)
      and MAP kinase kinase kinase 1 (MEKK1), stimulate c-Jun kinase (JNK) activity and
      induce apoptosis. Transient transfection of dominant negative and constitutively
      active components of the JNK pathway in COS-7 cells showed that two G protein
      subunits, Galpha12 and Galpha13, stimulated the JNK pathway in a ASK1- and MEKK1
      dependent manner. Moreover, the mutationally activated Galpha12 and Galpha13
      stimulated the kinase activity of ASK1. Both Galpha12 and Galpha13 employ small
      GTPases, Cdc42 and Rac1, to transduce signal to MEKK1 and, subsequently, to JNK.
      However, activation of JNK by Cdc42 and Rac1 did not require ASK1. Additionally,
      ASK1 and MEKK1 are involved in the apoptosis induced by Galpha12 and Galpha13. We
      conclude that Galpha12 and Galpha13 can induce apoptosis using two separate MAP
      kinase pathways; one is initiated by ASK1, and the other is initiated by MEKK1.
      Furthermore, Bcl-2 can block apoptosis induced by Galpha12 and Galpha13. This
      death-sparing function was associated with increased Bcl-2 phosphorylation,
      suggesting that phosphorylation of Bcl-2 may be a critical mechanism protecting
      cells from Galpha12- and Galpha13-induced apoptosis.

PMID- 9774393
TI  - Schistosoma mansoni Ca2+-ATPase SMA2 restores viability to yeast Ca2+-ATPase
      deficient strains and functions in calcineurin-mediated Ca2+ tolerance.
AB  - The sarco(endo)plasmic reticulum of animal cells contains an ATP-powered Ca2+
      pump that belongs to the P-type family of membrane-bound cation-translocating
      enzymes. In Schistosoma mansoni, the sarco(endo)plasmic reticulum Ca2+-ATPase
      (SERCA) is encoded by the SMA1 and SMA2 genes. A full-length SMA2 cDNA clone was
      isolated, sequenced, and expressed into a yeast Ca2+-ATPase-deficient strain
      requiring plasmid-borne rabbit SERCA1a for viability. The S. mansoni Ca2+-ATPase
      supports growth of mutant cells lacking SERCA1a, indicating functional expression
      in yeast and a role in calcium sequestration. Subcellular fractionation showed
      that the SMA2 ATPase is localized in yeast internal membranes. SMA2 expression
      was found to be associated with thapsigargin-sensitive, Ca2+-dependent ATPase
      activity. The activity increased 2-fold upon calcineurin inactivation, which
      correlates with in vivo stimulated contribution of SMA2 in calcium tolerance.
      These results suggest that calcineurin controls calcium homeostasis by inhibiting
      Ca2+-ATPase activity in an internal compartment.

PMID- 9774394
TI  - Truncations at the NH2 terminus of rhodanese destabilize the enzyme and decrease
      its heterologous expression.
AB  - Rhodanese mutants containing sequential NH2-terminal deletions were constructed
      to test the distinct contributions of this region of the protein to expression,
      folding, and stability. The results indicate that the first 11 residues are
      nonessential for folding to the active conformation, but they are necessary for
      attaining an active, stable structure when expressed in Escherichia coli.
      Rhodanese species with up to 9 residues deleted were expressed and purified.
      Kinetic parameters for the mutants were similar to those of the full-length
      enzyme. Compared with shorter truncations, mutants missing 7 or 9 residues were
      (a) increasingly inactivated by urea denaturation, (b) more susceptible to
      inactivation by dithiothreitol, (c) less able to be reactivated, and (d) less
      rapidly inactivated by incubation at 37 degreesC. Immunoprecipitation showed that
      mutants lacking 10-23 NH2-terminal amino acids were expressed as inactive species
      of the expected size but were rapidly eliminated. Cell-free
      transcription/translation at 37 degreesC showed mutants deleted through residue 9
      were enzymatically active, but they were inactive when deleted further, just as
      in vivo. However, at 30 degreesC in vitro, both Delta1-10 and Delta1-11 showed
      considerable activity. Truncations in the NH2 terminus affect the chemical
      stability of the distantly located active site. Residues Ser-11 through Gly-22,
      which form the NH2-proximal alpha-helix, contribute to folding to an active
      conformation, to resisting degradation during heterologous expression, and to
      chemical stability in vitro.

PMID- 9774396
TI  - Developmentally regulated, alternative RNA splicing-generated pectoral muscle
      specific troponin T isoforms and role of the NH2-terminal hypervariable region in
      the tolerance to acidosis.
AB  - The structure-function relationship of the alternative RNA splicing-generated NH2
      terminal variable region of troponin T (TnT) is essential for understanding the
      physiological significance of developmental or muscle-specific TnT isoforms.
      Representing the hypervariable nature of the NH2-terminal region, a repeating
      transition metal-binding sequence (H(E/A)EAH)4-7 (Tx) has been found in chicken
      fast skeletal muscle TnT. In the present study, the developmentally regulated
      pectoral muscle-specific expression of this novel TnT isoform has been
      characterized. It was found that the variable amino terminus determined the
      isoelectric points of the TnT isoforms expressed, and the adult muscle-specific
      inclusion of the Tx sequence resulted in pectoralis TnTs, which were
      significantly more acidic in their NH2-terminal segment versus gastrocnemius
      TnTs. Experiments testing the effect of pH on TnT interaction with troponin I and
      tropomyosin indicated that although the interaction of acidic TnT isoforms with
      troponin I was less sensitive to the decrease of pH than the basic TnTs, the
      binding affinity of acidic TnT isoforms with tropomyosin was minimally affected
      by the decreased pH in contrast to basic TnT isoforms. Given that the majority of
      adult skeletal muscles express basic fast TnT isoforms, the switching between
      acidic and basic TnT isoforms may play a role in the functional adaptation of
      muscle to acidosis.

PMID- 9774395
TI  - Highly sulfated dermatan sulfates from Ascidians. Structure versus anticoagulant
      activity of these glycosaminoglycans.
AB  - Dermatan sulfates with the same backbone structure [4-alpha-L-IdceA-1-->3-beta-D
      GalNAc-1]n but with different patterns of sulfation substitutions have been
      isolated from the ascidian body. All the ascidian dermatan sulfates have a high
      content of 2-O-sulfated alpha-L-iduronic acid residues but differ in the pattern
      of sulfation of the N-acetyl-beta-D-galactosamine units. Styela plicata and
      Halocynthia pyriformis have 4-O-sulfated units, but in Ascidian nigra they are 6
      O-sulfated. This collection of ascidian dermatan sulfates (together with native
      and oversulfated mammalian dermatan sulfate), where the extent and position of
      sulfate substitution have been fully characterized, were tested in anticoagulant
      assays. Dermatan sulfate from A. nigra has no discernible anticoagulant activity,
      which indicates that 4-O-sulfation of the N-acetyl-beta-D-galactosamine is
      essential for the anticoagulant activity of this glycosaminoglycan. In contrast
      dermatan sulfates from S. plicata and H. pyriformis are potent anticoagulants due
      to potentiation of thrombin inhibition by heparin cofactor II. These ascidian
      dermatan sulfates have approximately 10-fold and approximately 6-fold higher
      activity with heparin cofactor II than native and an oversulfated mammalian
      dermatan sulfate, respectively. They have no effect on thrombin or factor Xa
      inhibition by antithrombin. These naturally oversulfated ascidian dermatan
      sulfates are sulfated at selected sites required for interaction with heparin
      cofactor II and thus have specific and potent anticoagulant activity.

PMID- 9774397
TI  - Stereoselectivity of human nucleotide excision repair promoted by defective
      hybridization.
AB  - To assess helical parameters that dictate fast or slow removal of carcinogen-DNA
      adducts, we probed human nucleotide excision repair (NER) activity with DNA
      containing L-deoxyriboses. Unlike natural lesions such as pyrimidine dimers or
      base adducts, L-deoxyribonucleosides (the mirror images of normal D
      deoxyribonucleosides) involve neither the addition nor the loss of covalent bonds
      or functional groups and hence exclude modulation of repair efficiency by adduct
      chemistry and size. Previous studies showed that single L-deoxyribonucleosides
      distort DNA backbones but are accommodated in the double helix with intact
      hydrogen bonding between complementary strands. Here, we found that such single L
      enantiomers are rejected as excision repair substrates in a NER-proficient cell
      extract. However, the same L-deoxyribose moiety stimulates NER activity upon
      incorporation into a nonhybridizing site of one or, more effectively, two base
      mismatches. In contrast to single L-deoxyriboses, multiple consecutive L
      deoxyriboses interfere with normal hybridization; in this case, the intrinsic
      derangement of base pairing was sufficient to promote the excision of a cluster
      of three adjacent L-deoxyribonucleosides without any requirement for mismatches.
      Thus, using stereoselective substrates, we demonstrate the participation of a
      recognition subunit that guides human NER activity to sites of defective Watson
      Crick strand pairing. This conformational sensor detects labile hydrogen bonds
      irrespective of the type of deoxyribonucleotide modification.

PMID- 9774398
TI  - Deletions in the second stalk of F1F0-ATP synthase in Escherichia coli.
AB  - In Escherichia coli F1F0-ATP synthase, the two b subunits form the second stalk
      spanning the distance between the membrane F0 sector and the bulk of F1. Current
      models predict that the stator should be relatively rigid and engaged in contact
      with F1 at fixed points. To test this hypothesis, we constructed a series of
      deletion mutations in the uncF(b) gene to remove segments from the middle of the
      second stalk of the subunit. Mutants with deletions of 7 amino acids were
      essentially normal, and those with deletions of up to 11 amino acids retained
      considerable activity. Membranes prepared from these strains had readily
      detectable levels of F1-ATPase activity and proton pumping activity. Removal of
      12 or more amino acids resulted in loss of oxidative phosphorylation. Levels of
      membrane-associated F1-ATPase dropped precipitously for the longer deletions, and
      immunoblot analysis indicated that reductions in activity correlated with reduced
      levels of b subunit in the membranes. Assuming the likely alpha-helical
      conformation for this area of the b subunit, the 11-amino acid deletion would
      result in shortening the subunit by approximately 16 A. Since these deletions did
      not prevent the b subunit from participating in productive interactions with F1,
      we suggest that the b subunit is not a rigid rodlike structure, but has an
      inherent flexibility compatible with a dynamic role in coupling.

PMID- 9774399
TI  - Mutation at histidine 338 of gp91(phox) depletes FAD and affects expression of
      cytochrome b558 of the human NADPH oxidase.
AB  - Defective NADPH oxidase components prevent superoxide (O-2) generation, causing
      chronic granulomatous disease (CGD). X-linked CGD patients have mutations in the
      gene encoding the gp91(phox) subunit of cytochrome b558 and usually lack
      gp91(phox) protein completely (X91(0)). gp91(phox) is considered to be a
      flavocytochrome that contains binding sites for NADPH, FAD, as well as heme. We
      here report a rare X-linked CGD patient whose neutrophils entirely failed to
      produce O-2, but presented a diminished expression of gp91(phox) containing about
      one-third of the heme present in normal individuals by Soret absorption.
      Translocation of cytosolic factors p67(phox) and p47(phox) was normal. However,
      the FAD content in his neutrophil membranes was as low as that of X91(0)
      patients, suggesting complete depletion of FAD in his gp91(phox). This was in
      agreement with the finding that a single base substitution (C1024 to T) changed
      His-338 to Tyr in gp91(phox) in a predicted FAD-binding domain of the
      flavocytochrome model. The loss of FAD could not be corrected even after addition
      of reagent FAD or a FAD-rich dehydrogenase fraction isolated from normal
      neutrophils to the patient's membranes, in a reconstitution in vitro with normal
      cytosol. These results indicate that His-338 is a very critical residue for FAD
      incorporation into the NADPH oxidase system. This is the first such mutation
      found in CGD.

PMID- 9774400
TI  - Clusterin biogenesis is altered during apoptosis in the regressing rat ventral
      prostate.
AB  - Clusterin was first characterized as an apoptosis-associated transcript after it
      was identified as testosterone-repressed prostate message (TRPM-2) that is
      expressed in the epithelial cells of the regressing rat ventral prostate.
      Increases in clusterin mRNA and protein have been consistently detected in
      apoptotic cell death paradigms, establishing clusterin gene expression as a
      prominent marker of apoptotic cell loss. However, enhanced protein expression has
      also been reported in surviving cells. This ambiguity makes it difficult to
      define the contribution of clusterin to apoptosis. To address this problem, a
      panel of polyclonal and monoclonal antibodies were raised against the clusterin
      alpha-chain, beta-chain, and mixed alpha/beta epitopes. These antibodies detect
      changes in the biogenesis of clusterin during apoptosis by Western analysis and
      immunohistochemistry. A 42-kDa glyco/isoform of clusterin appears to be up
      regulated in dying epithelial cells. This glyco/isoform is apparently generated
      as a result of apoptosis-induced stimulation of a normal but under-utilized,
      synthetic pathway. These data demonstrate that clusterin synthesized by apoptotic
      cells can be immunologically distinguished from clusterin synthesized by
      surviving cells in damaged tissue.

PMID- 9774401
TI  - A balance of opposing signals within the cytoplasmic tail controls the lysosomal
      targeting of P-selectin.
AB  - The 35-amino acid cytoplasmic tail of the adhesion receptor P-selectin is
      subdivided into stop transfer, C1 and C2 domains. It contains structural signals
      needed for targeting this protein to specialized secretory organelles and to
      lysosomes. Recently, using site-directed mutagenesis of horseradish peroxidase-P
      selectin chimeras, we have uncovered a novel sequence within the C1 domain, KCPL,
      that mediates sorting from early, transferrin-positive endosomes to lysosomes and
      therefore operates as a positive lysosomal targeting signal (Blagoveshchenskaya,
      A. D., Norcott, J. P. , and Cutler, D. F. (1998) J. Biol. Chem. 273, 2729-2737).
      In the current study, we examined lysosomal targeting by both subcellular
      fractionation and an intracellular proteolysis assay and found that a balance of
      positive and negative signals is required for proper lysosomal sorting of P
      selectin. First, we have found that within the sequence KCPL, Cys-766 plays a
      major role along with Pro-767, whereas Lys-765 and Leu-768 make no contribution
      to promoting lysosomal targeting. In addition, horseradish peroxidase-P-selectin
      chimeras were capable of acylation in vivo with [3H]palmitic acid at Cys-766,
      since no labeling of a chimera in which Cys-766 was replaced with Ala was
      detected. Second, analysis of mutations within the C2 domain revealed that
      substitution of two sequences, YGVF and DPSP, causes an increase in both
      lysosomal targeting and intracellular proteolysis suggesting the presence of
      lysosomal avoidance signals. The inhibition or promotion of lysosomal targeting
      resulted from alterations in endosomal sorting since internalization was not
      changed in parallel with lysosomal delivery. Analysis of the double mutants
      KCPL/YGVF or KCPL/DPSP revealed that although the positive lysosomal targeting
      signal operates in the early/sorting transferrin-positive endosomes, the negative
      lysosomal targeting (lysosomal avoidance) signals act at later stages of the
      endocytic pathway, most likely in late endosomal compartments.

PMID- 9774403
TI  - Regulation of the p21-activated kinase-related Dictyostelium myosin I heavy chain
      kinase by autophosphorylation, acidic phospholipids, and Ca2+-calmodulin.
AB  - The Dictyostelium myosin I heavy chain kinase (MIHCK) is a member of the p21
      activated kinase family (Lee, S.-F., Egelhoff, T. T., Mahasneh, A., and Cote, G.
      P. (1996) J. Biol. Chem. 271, 27044-27048). MIHCK incubated with MgATP in the
      absence of effectors incorporates 1 mol of phosphate/mol, resulting in an
      approximately 40-fold increase in kinase activity. Sequence analysis of tryptic
      peptides has identified the major site of phosphorylation as Ser-8. A peptide and
      a glutathione S-transferase fusion protein containing the Ser-8 phosphorylation
      site were good substrates for MIHCK, indicating that MIHCK can catalyze its own
      activation. Guanosine 5'-3-O-(thio)triphosphate (GTPgammaS)-Rac1 stimulates MIHCK
      autophosphorylation and kinase activity 10-fold. Phosphatidylserine,
      phosphatidylinositol, and phosphatidylinositol 4,5-bisphosphate, but not
      phosphatidylcholine or sphingosine, were as effective as GTPgammaS-Rac1 in
      enhancing MIHCK autophosphorylation and activity. Acidic lipids and GTPgammaS
      Rac1 induced the autophosphorylation of a similar set of sites as judged by two
      dimensional tryptic peptide maps. It is proposed that GTP-Rac and acidic
      phospholipids function cooperatively to associate MIHCK with membranes. Ca2+
      calmodulin bound MIHCK and inhibited activation by acidic phospholipids but not
      by GTPgammaS-Rac1. These studies reveal a number of similarities between the
      regulatory properties of the Dictyostelium and Acanthamoeba MIHCK, suggesting
      that the signaling pathways that control myosin I are conserved.

PMID- 9774402
TI  - Metallothionein induction in response to restraint stress. Transcriptional
      control, adaptation to stress, and role of glucocorticoid.
AB  - Metallothioneins (MT) have been implicated in the protection of cells from
      oxidative stress. We studied the molecular mechanism of induction of MT-I and MT
      II in response to restraint stress using a mouse model system in which the
      animals were restrained in well ventilated polypropylene tubes for 12 h each day
      (one cycle). Here, we show that MT-I and MT-II mRNA levels were elevated as much
      as 10-20-fold after just one cycle of this simple stress. Stress-mediated MT
      induction occurred at the transcriptional level. The level of MT mRNA correlated
      with the stress-induced increase, and not with the diurnal variation, in the
      level of serum glucocorticoid. Treatment of the mice with RU 486, a
      glucocorticoid receptor antagonist, prior to restraint stress inhibited MT
      induction by at least 50%. Furthermore, the glucocorticoid responsive element
      binding activity in the liver nuclear extracts from the stressed mice was
      significantly higher than that in the control mice. The complex formations
      between the transcription factor Sp1, MTF1, or MLTF/ARE and the respective
      specific oligonucleotides were not altered in the liver from the stressed mouse.
      The MT mRNA levels returned to the basal level at the end of nine cycles of
      stress, indicating habituation of the animals to restraint stress. At this stage,
      exposure of the animals to another type of stress, treatment with heavy metals,
      resulted in further induction of MT. These data indicate that glucocorticoid is
      the primary physiological factor responsible for MT induction following restraint
      stress, and the glucocorticoid receptor is the major transcription factor
      involved in this process.

PMID- 9774404
TI  - Activation of factor VIII by thrombin increases its affinity for binding to
      synthetic phospholipid membranes and activated platelets.
AB  - Membrane-bound thrombin-activated factor VIII (fVIIIa) functions as a cofactor
      for factor IXa in the factor Xase complex. We found that binding of
      heterotrimeric fVIIIa (A1.A2.A3-C1-C2) to synthetic vesicles with a physiologic
      content of 4% phosphatidylserine (PS), 76% phosphatidylcholine, and 20%
      phosphatidylethanolamine occurs with a 10-fold higher affinity than that of
      factor VIII (fVIII). The increased affinity of fVIIIa for PS-containing membranes
      resulted from the reduced rate of fVIIIa dissociation from the vesicles compared
      with that of fVIII. Similar affinities of A3-C1-C2, A1.A2. A3-C1-C2, and A3-C1
      C2.heavy chain for interaction with PS-containing membranes demonstrate that
      removal of the light chain (LCh) acidic region by thrombin is responsible for
      these increased affinities of fVIIIa and its derivatives. Similar kinetic
      parameters of fVIII and its LCh and C2 domain for binding to PS-containing
      membranes and to activated platelets indicated that the C2 domain is entirely
      responsible for the interaction of fVIII with membranes. We conclude that the
      increased fVIIIa affinity for PS-containing membranes is a result of
      conformational change(s) within the C2 domain upon removal of the acidic region
      of the LCh. This conclusion is based on the finding that binding of the
      monoclonal antibody ESH8 to the C2 domain, which is known to prevent this
      conformational transition, resulted in fVIIIa binding to
      PS/phosphatidylcholine/phosphatidylethanolamine vesicles (4/76/20) with a lower
      affinity similar to that of fVIII. In addition, stabilization of the low affinity
      binding conformation of the C2 domain of fVIIIa by this antibody led to an
      inhibition of the fVIIIa activity in the factor X activation complex.

PMID- 9774405
TI  - A novel, non-redox-regulated NAD-dependent malate dehydrogenase from chloroplasts
      of Arabidopsis thaliana L.
AB  - We report a novel plastidic NAD-dependent malate dehydrogenase (EC 1. 1.1.37),
      which is not redox-regulated in contrast to its NADP-specific counterpart (EC
      1.1.1.82). Analysis of isoenzyme patterns revealed a single NAD-MDH associated
      with highly purified chloroplasts isolated from Arabidopsis and spinach. A cDNA
      clone encoding the novel enzyme was found in the Arabidopsis EST data base by
      sorting all putative clones for NAD-dependent malate dehydrogenase. A derived
      amino acid sequence is very similar to mitochondrial and peroxisomal NAD-MDHs
      within the region coding for the mature protein but possesses a 80-amino acid
      long N-terminal domain with typical characteristics of a chloroplast transit
      peptide. In vitro synthesized labeled precursor protein was imported into the
      stroma of spinach chloroplasts and processed to a mature enzyme subunit of 34
      kDa. Expressed in Escherichia coli, the recombinant enzyme exhibited the same
      distinctive isoelectric point of 5.35 as the original enzyme from Arabidopsis
      chloroplasts. Northern analysis revealed that the protein is expressed in both
      autotrophic and heterotrophic tissues. The findings reported here indicate that
      the "malate valve" operates not only in the illuminated chloroplasts but also in
      dark chloroplasts and in heterotrophic plastids and is therefore a general
      mechanism to maintain the optimal ratio between ATP and reducing equivalents in
      plastids.

PMID- 9774406
TI  - Efficient nuclear targeting of granzyme B and the nuclear consequences of
      apoptosis induced by granzyme B and perforin are caspase-dependent, but cell
      death is caspase-independent.
AB  - The secretory lysosomes of cytolytic lymphocytes house the principal apoptotic
      molecules for eliminating virus-infected cells: a membranolytic agent, perforin,
      and the serine protease, granzyme B. Perforin allows granzyme B access to
      cytosolic and nuclear substrates that, when cleaved, result in the characteristic
      apoptotic phenotype. Key among these substrates is a family of cytoplasmic
      caspases that mediate cell suicide. We have examined the caspase dependence of
      several nuclear and cytoplasmic parameters of apoptosis induced by purified
      perforin and granzyme B. Cell membrane leakage in response to perforin and
      granzyme B was independent of caspase activation; however, nuclear events such as
      DNA fragmentation and nuclear condensation and disintegration were abolished by
      the broad-acting caspase inhibitor, z-VAD-fmk. Despite being spared from nuclear
      damage, z-VAD-fmk-treated cells exposed to both cytotoxins uniformly died when
      they were re-cultured, while cells exposed to perforin or granzyme alone survived
      and proliferated as readily as untreated cells. Pretreatment of cells with z-VAD
      fmk also resulted in reduced granzyme B nuclear uptake following addition of
      perforin; however, its uptake into the cytoplasm in the absence of perforin was
      unaffected. We conclude that cell death in response to perforin and granzyme B
      does not require caspase activation and still proceeds efficiently through non
      nuclear pathways when nuclear substrate cleavage is inhibited.

PMID- 9774407
TI  - A long, weakly charged actin-binding loop is required for phosphorylation
      dependent regulation of smooth muscle myosin.
AB  - Chimeric substitution of the weak actin-binding loop (ABL) from chicken skeletal
      muscle myosin for that of gizzard smooth muscle heavy meromyosin (HMM) causes
      activation of the dephosphorylated mutant (SABL HMM; Rovner, A. S., Freyzon, Y.,
      and Trybus, K. M. (1995) J. Biol. Chem. 270, 30260-30263). The present study
      determined whether this loss of regulation is due to the greater positive charge
      density (5 versus 3 clustered lysine residues) or lesser length (14 versus 26
      residues) of the mutant ABL. Charge augmentation had little effect on regulation
      of expressed mutants, but elimination of the 12 N-terminal amino acids from the
      wild-type ABL significantly increased actin-activated ATPase activity of the
      dephosphorylated relative to the phosphorylated molecule while conferring the
      ability to move actin filaments in vitro on the former. Addition of the same 12
      residues to the SABL mutant increased the ratio of phosphorylated to
      dephosphorylated ATPase activity while imparting wild type-like regulation to
      motility. However, full actin activation of dephosphorylated ATPase activity
      required both the shorter length and greater positive charge density found in the
      SABL loop. These results demonstrate that, compared with skeletal, both the
      greater length and lesser positive charge density of the smooth muscle myosin ABL
      are required for proper phosphorylation-mediated regulation of the molecule.

PMID- 9774408
TI  - MTO1 codes for a mitochondrial protein required for respiration in paromomycin
      resistant mutants of Saccharomyces cerevisiae.
AB  - Mutations in MTO1 express a respiratory defect only in the context of a
      mitochondrial genome with a paromomycin-resistance allele. This phenotype is
      similar to that described previously for mss1 mutants by Decoster, E., Vassal,
      A., and Faye, G. (1993) J. Mol. Biol. 232, 79-88. We present evidence that Mto1p
      and Mss1p are mitochondrial proteins and that they form a heterodimer complex. In
      a paromomycin-resistant background, mss1 and mto1 mutants are inefficient in
      processing the mitochondrial COX1 transcript for subunit 1 of cytochrome oxidase.
      The mutants also fail to synthesize subunit 1 and show a pleiotropic absence of
      cytochromes a, a3, and b. In vivo pulse labeling of an mto1 mutant, however,
      indicate increased rates of synthesis of other mitochondrial translation
      products. The respiratory defective phenotype of mto1 and mss1 mutants is not
      seen in a paromomycin-sensitive genetic background. The visible absorption
      spectra of such strains indicate a higher ratio of cytochromes b/a and elevated
      NADH- and succinate-cytochrome c reductase activities. To explain these
      phenotypic characteristics, we proposed that the Mto1p.Mss1p complex plays a role
      in optimizing mitochondrial protein synthesis in yeast, possibly by a
      proofreading mechanism.

PMID- 9774410
TI  - Mutational analysis of poliovirus 2Apro. Distinct inhibitory functions of 2apro
      on translation and transcription.
AB  - Transient expression of poliovirus 2Apro in mammalian cells by means of the
      recombinant vaccinia virus vT7 expression system leads to drastic inhibition of
      both cellular and vaccinia virus gene expression (Aldabe, R., Feduchi, E., Novoa,
      I., and Carrasco, L. (1995) FEBS Lett. 377, 1-5; Aldabe, R., Feduchi, E., Novoa,
      I., and Carrasco, L. (1995) Biochem. Biophys. Res. Commun. 215, 928-936). To
      obtain further insights into the molecular basis of this inhibition, a number of
      2Apro variants were generated and expressed in COS-1 cells. The effect of these
      variants on cellular translation, on vaccinia virus-specific translation, and on
      transcription of the reporter gene luciferase was analyzed. The ability of the
      different 2Apro variants to block cellular translation depends on their
      capacities to cleave eIF-4G. The blockade exerted by 2Apro on transcription of
      the luciferase gene reinforces the notion that this protease is a potent
      inhibitor of RNA polymerase II-mediated transcription. Some of the 2Apro variants
      tested failed to block luciferase transcription, despite the fact that eIF-4G
      cleavage and inhibition of translation were observed. Two reconstituted
      polioviruses mutated in 2Apro were defective in inhibiting luciferase
      transcription, yet were still able to cleave eIF-4G and block translation. These
      findings indicate that 2Apro interferes with cellular gene expression at both the
      transcriptional and translational levels. Moreover, these two effects probably
      reflect the inactivation of different host proteins by poliovirus 2Apro.

PMID- 9774409
TI  - Flexibility of the neck region of the rieske iron-sulfur protein is functionally
      important in the cytochrome bc1 complex.
AB  - The crystal structure of the mitochondrial cytochrome bc1 complex suggests that
      movement of the extramembrane (head) domain of the Rieske iron-sulfur protein
      (ISP) is involved in electron transfer. Such movement requires flexibility in the
      neck region of ISP. To test this hypothesis, Rhodobacter sphaeroides mutants
      expressing His-tagged cytochrome bc1 complexes with altered ISP necks (residues
      39-48) were generated and characterized. Mutants with increased rigidity of the
      neck, generated by a double-proline substitution at Ala-46 and Ala-48 (ALA-PLP)
      or by a triple-proline substitution of ADV at residues 42-44 (ADV-PPP), have
      retarded (50%) or no photosynthetic growth, respectively. However, the mutant
      with a shortened neck, generated by deleting ADV (DeltaADV), has a photosynthetic
      growth rate comparable to that of complement cells, indicating that the length of
      the ISP neck is less critical than its flexibility in support of photosynthetic
      growth. The DeltaADV and ALA-PLP mutant membranes have 10 and 30% of the
      cytochrome bc1 complex activity found in the complement membrane, respectively,
      whereas the ADV-PPP mutant membrane contains no cytochrome bc1 complex activity.
      The loss of cytochrome bc1 complex activity in the DeltaADV membrane is
      attributed to improper docking of the head domain of ISP on cytochrome b, as
      indicated by a drastic change in the EPR characteristics of the Rieske iron
      sulfur cluster. The loss of cytochrome bc1 complex activity in the ALA-PLP and
      ADV-PPP mutant membranes results from the decreased mobility of the ISP head
      domain due to the increased rigidity of the ISP neck. The ALA-PLP mutant complex
      has a larger activation energy than the wild-type complex, suggesting that
      movement of the head domain decreases the activation energy barrier of the
      cytochrome bc1 complex. Using the conditions developed for the isolation of the
      His-tagged complement cytochrome bc1 complex, a two-subunit complex (cytochromes
      b and c1) was obtained from the DeltaADV and ADV-PPP mutants, indicating that
      mutations at the neck region of ISP weaken the interactions among cytochrome b,
      ISP, and subunit IV.

PMID- 9774411
TI  - The heme prosthetic group of lactoperoxidase. Structural characteristics of heme
      l and heme l-peptides.
AB  - The heme prosthetic group from the bovine milk enzyme lactoperoxidase (LPO),
      termed heme l, is isolated through an approach that combines proteolytic
      hydrolysis and reverse-phase high performance liquid chromatographic separation
      of the resulting digest. Application of different proteases yields either a
      peptide-bound heme (with trypsin and chymotrypsin) or a peptide-free heme (with
      proteinase K). Both heme l and heme l-peptide species were investigated by
      paramagnetic 1H NMR spectroscopy, electrospray mass spectrometry, and peptide
      sequence analysis. Paramagnetic 1H NMR experiments on the low spin bis(cyano)
      Fe(III)heme l complex conclusively define the heme l structure as a 1,5
      bis(hydroxymethyl) derivative of heme b. The electrospray mass spectrum of heme l
      confirms the two-site hydroxyl functionalization on this heme. Paramagnetic 1H
      NMR spectra of the high spin bis(dimethyl sulfoxide)-Fe(III) complexes of the
      isolated heme species provide information regarding peptide content. Sequence
      analyses of peptides released from two heme l-peptide species by base hydrolysis
      suggest that heme-protein ester linkages in lactoperoxidase occur between the two
      hydroxyl groups of heme l and the carboxylic side chains of glutamate 275 and
      aspartate 125. These results confirm the earlier reported structural proposal
      (Rae, T. D., and Goff, H. M. (1996) J. Am. Chem. Soc. 118, 2103-2104).

PMID- 9774412
TI  - Molecular cloning and functional expression of a Caenorhabditis elegans
      aminopeptidase structurally related to mammalian leukotriene A4 hydrolases.
AB  - In a search of the Caenorhabditis elegans DNA data base, an expressed sequence
      tag of 327 base pairs (termed cm01c7) with strong homology to the human
      leukotriene A4 (LTA4) hydrolase was found. The use of cm01c7 as a probe, together
      with conventional hybridization screening and anchored polymerase chain reaction
      techniques resulted in the cloning of the full-length 2.1 kilobase pair C.
      elegans LTA4 hydrolase-like homologue, termed aminopeptidase-1 (AP-1). The AP-1
      cDNA was expressed transiently as an epitope-tagged recombinant protein in COS-7
      mammalian cells, purified using an anti-epitope antibody affinity resin, and
      tested for LTA4 hydrolase and aminopeptidase activities. Despite the strong
      homology between the human LTA4 hydrolase and C. elegans AP-1(63% similarity and
      45% identity at the amino acid level), reverse-phase high pressure liquid
      chromatography and radioimmunoassay for LTB4 production revealed the inability of
      the C. elegans AP-1 to use LTA4 as a substrate. In contrast, the C. elegans AP-1
      was an efficient aminopeptidase, as demonstrated by its ability to hydrolyze a
      variety of amino acid p-nitroanilide derivatives. The aminopeptidase activity of
      C. elegans AP-1 resembled that of the human LTA4 hydrolase/aminopeptidase enzyme
      with a preference for arginyl-p-nitroanilide as a substrate. Hydrolysis of the
      amide bond of arginyl-p-nitroanilide was inhibited by bestatin with an IC50 of
      2.6 +/- 1.2 microM. The bifunctionality of the mammalian LTA4 hydrolase is still
      poorly understood, as the physiological substrate for its aminopeptidase activity
      is yet to be discovered. Our results support the idea that the enzyme originally
      functioned as an aminopeptidase in lower metazoa and then developed LTA4
      hydrolase activity in more evolved organisms.

PMID- 9774413
TI  - A carboxyl-terminal extension of the zinc finger domain contributes to the
      specificity and polarity of peroxisome proliferator-activated receptor DNA
      binding.
AB  - Heterodimers of the peroxisome proliferator-activated receptors (PPAR) and the
      retinoid X receptors (RXR) recognize response elements (PPREs) that exhibit the
      consensus sequence 5'-A(A/T)CT(A/G)GGNCAAAG(G/T)TCA-3'. The consensus PPRE
      includes both a 5'-extension and a direct repeat (DR1) comprised of two canonical
      core recognition sequences (underlined) for nuclear receptor zinc fingers
      separated by a single nucleotide spacer. The extended binding site recognized by
      PPARs is very similar to sites that bind monomers of the nuclear receptors Rev
      ErbA and ROR suggesting that the latter could bind to PPREs and affect gene
      transcription. However, Rev-ErbA and ROR bind weakly to naturally occurring PPREs
      relative to the consensus binding site, and significant effects on PPARalpha
      transactivation of a CYP4A6-Z reporter were not observed. In contrast, PPAR/RXR
      heterodimers bind to a DR2 element containing the conserved 5'-extended sequence
      that is recognized by dimers of RORalpha or Rev-ErbA. PPARalpha/RXRalpha
      positively regulate transcription from this element, and co-expression of Rev
      ErbA blocks this effect. The nuclear receptors NGFI-B and ROR utilize a carboxyl
      terminal extension (CTE) of the zinc finger DNA binding domain in their
      interactions with the 5'-extension of a single zinc finger-binding site. DNA
      binding domains (DBD) of PPARs alpha, delta, and gamma that contain the zinc
      finger motif and a CTE display binding to core recognition sequences that is
      dependent on the 5'-extended sequence found in PPREs. Unlike DBDs of other
      nuclear receptors that form heterodimers with RXR, the PPAR-DBDs did not exhibit
      cooperative binding with the DBD of RXR and exhibit the opposite polarity for
      binding to the direct repeat motif. In contrast to the corresponding DBD of RXR,
      the PPAR-DBDs bind as monomers to a single extended binding site as well as to
      the consensus PPRE. A chimera linking the zinc finger domain of RXRalpha to the
      CTE from PPARalpha bound to a single extended binding site indicating a
      functional role for the CTE of PPARs in extended binding site recognition.

PMID- 9774414
TI  - The retinoic acid and cAMP-dependent up-regulation of 3-O-sulfotransferase-1
      leads to a dramatic augmentation of anticoagulantly active heparan sulfate
      biosynthesis in F9 embryonal carcinoma cells.
AB  - Retinoic acid (RA) and dibutyryl cAMP plus theophilline (CT) trigger F9 cells to
      differentiate into parietal endoderm. The differentiation induces a 9-fold
      increase in total heparan sulfate (HStotal) biosynthesis and a 170-fold increase
      in anticoagulantly active HS (HSact) biosynthesis. Measurement of 3-O
      sulfotransferase-1 mRNA and enzymatic activity demonstrated an increase of over
      100-fold whereas determination of N-, 2-O, and 6-O-sulfotransferase enzymatic
      activities showed elevations of 2-, 3. 5-, and 3.7-fold, respectively. HSact
      precursor pool measurements reveal that 30% of control F9 HStotal can be
      converted into HSact while only an additional 10% of RACT F9 HStotal can be
      transformed into HSact. Disaccharide analysis of metabolic labeled HS indicated
      that 32% 3-O-sulfate containing disaccharides, i.e. GlcA-anManR3S and GlcA
      anManR3S6S, are present in HSact and 68% GlcA-anManR3S and GlcA-anManR3S6S are
      found in anticoagulantly inactive HS (HSinact). By using adenosine 3'-phosphate
      5'-phosphosulfate and purified 3-O-sulfotransferase-1, 30% of 3-O-sulfation
      occurs in HSact and 70% of 3-O-sulfation occurs in HSinact. The similar ratio of
      3-O-sulfate distribution in HSact versus HSinact suggests that HSact production
      in the F9 system is determined by the abundance of 3-O-sulfotransferase-1 as well
      as the size of the HSact precursor pool. Extensively 3-O-sulfated HSinact may
      play an important functional role under in vivo conditions within the murine
      placenta.

PMID- 9774415
TI  - Optimization of cell surface binding enhances efficiency and specificity of
      molecular conjugate gene delivery.
AB  - Molecular conjugates, or polyplexes, are promising synthetic vectors for
      targeted, in vivo gene delivery, if their efficiency can be improved. Gaining
      mechanistic information on conjugate gene delivery can potentially yield
      significant improvements in transfer efficiency by revealing barriers to
      conjugate transfer from the cell surface to the nucleus. We have developed an
      experimental system that employs epidermal growth factor as the ligand to direct
      delivery of DNA encoding the green fluorescent protein to mouse fibroblasts. We
      report here that the initial step of delivery, binding of the conjugate to the
      cell surface, is a barrier to gene transfer. We examined the effects of conjugate
      charge, ligand cross-linker spacer length, and ligand valency on polyplex cell
      surface binding, internalization, and gene transfer. We find that delivery is
      both efficient and specific only within a relatively narrow window of conjugate
      charge, results that correlate with binding and internalization of radiolabeled
      conjugate. In addition, increasing the cross-linker length can improve binding
      affinity and delivery. Finally, there is a significant optimum in gene delivery
      as a function of ligand valency, due to saturation of receptor binding and
      internalization. Optimizing parameters that affect surface binding therefore
      improves the efficiency and specificity of molecular conjugate gene delivery.

PMID- 9774416
TI  - The effect of human beta2-microglobulin on major histocompatibility complex I
      peptide loading and the engineering of a high affinity variant. Implications for
      peptide-based vaccines.
AB  - The ability to directly load cell surface major histocompatibility complex (MHC)
      class I molecules with peptides provides a potentially powerful approach toward
      the development of vaccines to generate cell-mediated immunity. We demonstrate
      that exogenous beta2-microglobulin (beta2m) stabilizes human cell surface MHC I
      molecules and facilitates their loading with exogenous peptides. Additionally,
      using three-dimensional crystal structures and known interaction sites between
      MHC I heavy chains and beta2m, we engineered variants of human beta2m (hbeta2m)
      with a single serine substitution at residue 55. This alteration was predicted to
      promote hydrophobic interactions at the MHC I heavy chain/beta2m interface and
      displace an ordered water molecule. Compared with hbeta2m, the serine to valine
      substitution at residue 55 had improved ability to bind to cell surface HLA-A1,
      HLA-A2, and HLA-A3 molecules, facilitate exogenous peptide loading, and promote
      recognition by peptide-specific T cells. The inclusion of hbeta2m or higher
      affinity variants when pulsing cells with MHC-restricted peptides increases the
      efficiency of peptide loading 50-80-fold. Therefore, the inclusion of hbeta2m in
      peptide-based vaccines may increase cell surface antigen densities above
      thresholds that allow recognition of peptide antigens by the immune system,
      particularly for cryptic, subdominant, or marginally antigenic peptides.

PMID- 9774417
TI  - Coiled-coil interaction of N-terminal 36 residues of cyclase-associated protein
      with adenylyl cyclase is sufficient for its function in Saccharomyces cerevisiae
      ras pathway.
AB  - In the budding yeast Saccharomyces cerevisiae, association with the 70-kDa
      cyclase-associated protein (CAP) is required for proper response of adenylyl
      cyclase to Ras proteins. We show here that a small segment comprising the N
      terminal 36 amino acid residues of CAP is sufficient for association with
      adenylyl cyclase as well as for its function in the Ras-adenylyl cyclase pathway
      as assayed by the ability to confer RAS2(Val-19)-dependent heat shock sensitivity
      to yeast cells. The CAP-binding site of adenylyl cyclase was mapped to a segment
      of 119 amino acid residues near its C terminus. Both of these regions contained
      tandem repetitions of a heptad motif alphaXXalphaXXX (where alpha represents a
      hydrophobic amino acid and X represents any amino acid), suggesting a coiled-coil
      interaction. When mutants of CAP defective in associating with adenylyl cyclase
      were isolated by screening of a pool of randomly mutagenized CAP, they were found
      to carry substitution mutations in one of the key hydrophobic residues in the
      heptad repeats. Furthermore, mutations of the key hydrophobic residues in the
      heptad repeats of adenylyl cyclase also resulted in loss of association with CAP.
      These results indicate the coiled-coil mechanism as a basis of the CAP-adenylyl
      cyclase interaction.

PMID- 9774419
TI  - Clotrimazole, an antimycotic drug, inhibits the sarcoplasmic reticulum calcium
      pump and contractile function in heart muscle.
AB  - Clotrimazole (CLT), an antimycotic drug, has been shown to inhibit proliferation
      of normal and cancer cell lines and its systemic use as a new tool in the
      treatment of proliferative disorders is presently under scrutiny (Benzaquen, L.
      R., Brugnara, C., Byers, H. R., Gattoni-Celli, S., and Halperin, J. A. (1995)
      Nature Med. 1, 534-540). The action of CLT is thought to involve depletion of
      intracellular Ca2+ stores but the underlying mechanism has not been defined. The
      present study utilized membrane vesicles of rabbit cardiac sarcoplasmic reticulum
      (SR) to determine the mechanism by which CLT depletes intracellular Ca2+ stores.
      The results revealed a strong, concentration-dependent inhibitory action of CLT
      on the ATP-energized Ca2+ uptake activity of SR (50% inhibition with
      approximately 35 microM CLT). The inhibition was of rapid onset (manifested in
      <15 s), and was accompanied by a 7-fold decrease in the apparent affinity of the
      SR Ca2+-ATPase for Ca2+ and a minor decrement in the enzyme's apparent affinity
      toward ATP. Exposure of SR to CLT in the absence or presence of Ca2+ resulted in
      irreversible inhibition of Ca2+ uptake demonstrating that the Ca2+-bound and Ca2+
      free conformations of the Ca2+-ATPase are CLT-sensitive. Introduction of CLT to
      the reaction medium subsequent to induction of enzyme turnover with Ca2+ and ATP
      resulted in instantaneous cessation of Ca2+ transport indicating that an
      intermediate enzyme species generated during turnover undergoes rapid
      inactivation by CLT. The inhibition of Ca2+ uptake by CLT was accompanied by
      inhibition of Ca2+-stimulated ATP hydrolysis and Ca2+-induced phosphoenzyme
      intermediate formation from ATP in the ATPase catalytic cycle. Phosphorylation of
      the Ca2+-deprived enzyme with Pi in the reverse direction of catalytic cycle and
      Ca2+ release from Ca2+-preloaded SR vesicles were unaffected by CLT. It is
      concluded that CLT depletes intracellular Ca2+ stores by inhibiting Ca2+
      sequestration by the Ca2+-ATPase. The mechanism of ATPase inhibition involves a
      drug-induced alteration in the Ca2+-binding site(s) resulting in paralysis of the
      enzyme's catalytic and ion transport cycle. CLT (50 microM) caused marked
      depression of contractile function in isolated perfused, electrically paced
      rabbit heart preparations. The contractile function recovered gradually following
      withdrawal of CLT from the perfusate indicating the existence of mechanisms in
      the intact cell to inactivate, metabolize, or clear CLT from its target site.

PMID- 9774418
TI  - Phosphoinositide 3-kinase regulation of T cell receptor-mediated interleukin-2
      gene expression in normal T cells.
AB  - Phosphoinositide (PI) 3-kinase has been implicated in T cell receptor (TCR)
      signaling, either as a positive or a negative regulatory molecule. Here, we show
      that for normal mouse lymph node T cells, PI 3-kinase activity is required for
      interleukin-2 (IL-2) production following TCR-mediated activation. Furthermore,
      in normal T cells, inhibition of PI 3-kinase prevented activation of enzymes in
      the extracellular signal-regulated protein kinase (ERK) signaling pathway (MEK-1
      and ERK-2). Overexpression of a dominant-negative mutant of PI 3-kinase and
      pharmacological inhibitors of PI 3-kinase prevented transcriptional activation of
      AP-1 and NF-AT, transcription factors regulated by ERK-2 and pivotal for IL-2
      gene expression. Although a constitutively active form of Akt kinase, a
      downstream mediator of PI 3-kinase function, enhanced TCR-induced IL-2 gene
      transcription, it could not bypass the requirement for PI 3-kinase activity.
      Therefore, PI 3-kinase is likely to be involved in signaling for IL-2 production
      in at least two steps in the TCR-initiated signaling pathway.

PMID- 9774420
TI  - Regulation of chemotactic and proadhesive responses to chemoattractant receptors
      by RGS (regulator of G-protein signaling) family members.
AB  - Serpentine Galphai-linked receptors support rapid adhesion and directed migration
      of leukocytes and other cell types. The intracellular mechanisms mediating and
      regulating chemoattractant-directed adhesion and locomotion are only now
      beginning to be explored. RGS (for regulator of G-protein signaling) proteins are
      a recently described family that regulate Galphai-stimulated pathways by acting
      as GTPase-activating proteins. Little is known about the GTPase activity of the
      Galphai proteins involved in adhesion and chemotaxis, or the significance of
      their regulation to these responses. Using transiently transfected lymphoid cells
      as a model system, we show that expression of RGS1, RGS3, and RGS4 inhibits
      chemoattractant-induced migration. In contrast, RGS2, a regulator of Galphaq
      activity, had no effect on cell migration to any chemoattractant. RGS1, RGS3, and
      RGS4 also reduced rapid chemoattractant-triggered adhesion, although the
      proadhesive response appears quantitatively less sensitive to RGS action than
      chemotaxis. The results suggest that the duration of the Galphai signal may be a
      particularly important parameter in the chemotactic responses of leukocytes, and
      demonstrate the potential for RGS family members to regulate cellular adhesive
      and migratory behaviors.

PMID- 9774421
TI  - Amino-terminal signal transducer and activator of transcription (STAT) domains
      regulate nuclear translocation and STAT deactivation.
AB  - The first approximately 100 amino acids of the STAT (signal transducer and
      activator of transcription) family of transcription factors share a high degree
      of sequence similarity. To determine whether they encode a functionally conserved
      domain, amino-terminal chimeric STATs were created. These chimeric STATs share a
      number of properties with wild-type Stat1, including a predominately cytoplasmic
      pattern of expression in unstimulated cells. Upon stimulation with ligand, the
      chimeric STATs rapidly become tyrosine-phosphorylated, dimerize, and are able to
      bind DNA. They are also able to heterodimerize with coexpressed wild-type Stat1.
      Yet in contrast to wild-type Stat1, the chimeric STATs exhibit a marked defect in
      deactivation. Moreover, the persistence of active chimeras correlates directly
      with an inability to translocate to the nucleus. The defects both in nuclear
      translocation and in deactivation are rescued by heterodimerization with
      coexpressed wild-type Stat1. This study indicates that STAT amino termini provide
      a signal that is important for nuclear translocation and, subsequently,
      deactivation. It also suggests that deactivation may depend on a prior nuclear
      localization event.

PMID- 9774423
TI  - Stat3 plays an important role in oncogenic Ros- and insulin-like growth factor I
      receptor-induced anchorage-independent growth.
AB  - The role of signal transducers and activators of transcription (STATs) in
      receptor protein-tyrosine kinase (PTK)-induced cell growth and transformation was
      investigated using an inducible epidermal growth factor receptor-Ros chimeric
      receptor called ER2 and a constitutively activated insulin-like growth factor I
      receptor called NM1, both of which are able to induce anchorage-independent
      growth of NIH 3T3 cells. ER2 and NM1 receptor PTKs are able to cause Stat3
      activation. Co-expressing the dominant negative Stat3 mutant with ER2 or NM1 in
      transiently or stable transfected cells resulted in a dramatic inhibition of
      colonies induced by these receptor PTKs and a moderate inhibition of their
      mitogenicity in monolayer. Therefore, Stat3 is not only important for initiation
      of transformation, as demonstrated by inhibition of the epidermal growth factor
      inducible colony formation of the ER2 cells by the mutant, but it is also
      required for the maintenance of transformation, as evidenced by reversion of the
      NM1 transformed cells. The DNA binding and transcriptional activities of the
      endogenous Stat3 were greatly inhibited in the ER2 and NM1 cells co-expressing
      the Stat3 mutants. We conclude that activated function of Stat3 is required for
      the establishment and maintenance of Ros and insulin-like growth factor I
      receptor PTK-induced cell transformation.

PMID- 9774422
TI  - Identification of apoptosis-associated proteins in a human Burkitt lymphoma cell
      line. Cleavage of heterogeneous nuclear ribonucleoprotein A1 by caspase 3.
AB  - Apoptosis or programmed cell death is essential in the process of controlling
      lymphocyte growth and selection. We identified proteins that are involved in anti
      IgM antibody-mediated apoptosis using a subclone of the human Burkitt lymphoma
      cell line BL60. Apoptosis-associated proteins were detected by high resolution
      two-dimensional gel electrophoresis on a micropreparative scale. Comparison of
      the high resolution two-dimensional gel electrophoresis protein patterns from
      apoptotic and non-apoptotic cells showed differences in approximately 80 spots
      including protein modifications. Analysis of the predominantly altered proteins
      was performed by internal Edman microsequencing and/or by peptide mass
      fingerprinting using matrix-assisted laser desorption/ionization mass
      spectrometry. Analysis was significantly improved by using new micropreparative
      high resolution two-dimensional gels employing high protein concentrations. The
      following 12 apoptosis-associated proteins were identified: heterogeneous nuclear
      ribonucleoprotein (hnRNP) A1, hnRNP C1/C2, FUSE-binding protein, dUTPase,
      lymphocyte-specific protein LSP1, UV excision repair protein RAD23 homologue B
      (HHR23B), 60 S acidic ribosomal protein P0 (L10E), heterochromatin protein 1
      homologue alpha (HP1alpha), nucleolin, lamin, neutral calponin, and actin.
      Fragmentation of actin, hnRNP A1, hnRNP C1/C2, 60 S acidic ribosomal protein P0,
      lamin, and nucleolin could be inhibited by benzyloxycarbonyl-Asp(OMe)-Glu(OMe)
      Val-Asp(OMe)-fluoromethyl ketone, a selective irreversible inhibitor of CPP32
      (caspase 3).

PMID- 9774424
TI  - Inhibition of the interaction between tyrosine-based motifs and the medium chain
      subunit of the AP-2 adaptor complex by specific tyrphostins.
AB  - Several intracellular membrane trafficking events are mediated by tyrosine
      containing motifs found within the cytosolic domains of certain integral membrane
      proteins. Many of these tyrosine motifs conform to the consensus YXXPhi (where
      Phi represents a bulky hydrophobic residue). This YXXPhi motif has been shown to
      interact with the medium chain subunits of adaptor complexes that generally link
      relevant integral membrane protein cytosolic domains to the clathrin coat
      involved in vesicle formation. The motif YXXPhi is also very similar to motifs
      that are targets for phosphorylation by tyrosine kinases. Tyrosine kinase
      inhibitors known as tyrphostins are structural analogues of tyrosine, and so it
      is possible that tyrphostins could also inhibit interactions between medium
      chains and YXXPhi motifs. TGN38 is a type I integral membrane protein containing
      a tyrosine motif, YQRL, within the cytosolic domain. We have previously shown
      that this motif interacts directly with the medium chain subunit of the plasma
      membrane localized AP-2 adaptor complex (mu2). We have investigated a range of
      tyrphostins and demonstrated a specific inhibition of the interaction between mu2
      and the TGN38 cytosolic domain by tyrphostin A23 through in vitro analysis and
      the yeast two-hybrid system. These data raise the exciting possibility that
      different membrane traffic events could be inhibited by specific tyrphostins.

PMID- 9774425
TI  - Mutant membrane protein toxicity.
AB  - This report describes an extensive mutational analysis of the most carboxyl
      terminal membrane-spanning sequence of Escherichia coli lac permease (TM12). In
      addition to identifying residues important for lactose transport function, the
      analysis revealed that numerous mutations made lac permease highly toxic to
      cells. In the most extreme cases, production of such proteins at very low steady
      state levels reduced cell viability greater than 10(4)-fold. Both frameshift and
      missense mutations led to toxicity, with the frameshift mutations having the
      strongest effects observed. The toxic missense mutations corresponded to changes
      in TM12 expected to interfere with membrane insertion or folding, such as the
      introduction of charged residues or prolines in the putative helix. The results
      suggest that cellular toxicity may be a relatively common consequence of
      mutations altering integral membrane protein folding. An analogous toxicity might
      contribute to the pathogenesis of several degenerative diseases caused by mutant
      membrane proteins, such as retinitis pigmentosa, Charcot-Marie-Tooth syndrome,
      and Alzheimer's disease.

PMID- 9774426
TI  - Negative charges in the C-terminal domain stabilize the alphaB-crystallin
      complex.
AB  - alphaB-Crystallin is one of the six known mammalian small heat-shock proteins
      (sHsps). These are characterized by the presence of a conserved sequence of 80
      100 residues, which constitutes the putative C-terminal domain. Like other sHsps,
      alphaB-crystallin forms multimeric globular complexes, often in combination with
      related sHsps. Here we show that in a yeast two-hybrid system, alphaB-crystallin
      can specifically interact with itself as well as with alphaA-crystallin and
      Hsp27. Analyses of the separate domains show that the conserved C-terminal domain
      (CalphaB) is essential for this interaction between subunits. To try and detect
      residues that are important in subunit interaction, the CalphaB domain was used
      in a two-hybrid screen as bait to select randomly mutated CalphaB mutants. In
      this way we obtained nine mutants that were still able to interact with wild-type
      CalphaB despite the presence of up to 15 replacements. Similarly, we obtained 16
      mutants that were unable to bind, because of the presence of just three to nine
      replacements. In binding CalphaB mutants, lysine residues were most often
      replaced by glutamic acid residues, and in non-binding CalphaB mutants, acidic
      residues were often found to be replaced by non-charged residues. This indicates
      that negative charges are important for subunit interaction and we propose a
      model to explain this role of acidic residues. Furthermore, we observed that two
      homologs of alphaB-crystallin, alphaA-crystallin and Hsp27, generally interact
      similarly with the binding and non-binding CalphaB mutants as does alphaB
      crystallin. This suggests that interactions involved in the complex formation of
      these three sHsps are largely comparable.

PMID- 9774427
TI  - Identification and cloning of prs a 1, a 32-kDa endochitinase and major allergen
      of avocado, and its expression in the yeast Pichia pastoris.
AB  - Avocado, the fruit of the tropical tree Persea americana, is a source of
      allergens that can elicit diverse IgE-mediated reactions including anaphylaxis in
      sensitized individuals. We characterized a 32-kDa major avocado allergen, Prs a
      1, which is recognized by 15 out of 20 avocado- and/or latex-allergic patients.
      Natural Prs a 1 was purified, and its N-terminal and two tryptic peptide
      sequences were determined. We isolated the Prs a 1 encoding cDNA by PCR using
      degenerate primers and 5'-rapid amplification of cDNA ends. The Prs a 1 cDNA
      coded for an endochitinase of 326 amino acids with a leader peptide of 25 amino
      acids. We expressed Prs a 1 in the yeast Pichia pastoris at 50 mg/liter of
      culture medium. The recombinant Prs a 1 showed endochitinase activity, inhibited
      growth and branching of Fusarium oxysporum hyphae, and possessed IgE binding
      capacity. IgE cross-reactivity with latex proteins including a 20-kDa allergen,
      most likely prohevein, was demonstrated, providing an explanation for the
      commonly observed cross-sensitization between avocado and latex proteins.
      Sequence comparison showed that Prs a 1 and prohevein had 70% similarity in their
      chitin-binding domains. Characterization of chitinases as allergens has
      implications for engineering transgenic crops with increased levels of
      chitinases.

PMID- 9774428
TI  - Critical amino acid residues in transmembrane span 7 of the serotonin transporter
      identified by random mutagenesis.
AB  - Transmembrane span 7 of the rat brain serotonin transporter was subjected to
      random mutagenesis. Of the 27 amino acid residues mutated, six were identified as
      functionally important by their sensitivity to nonconservative mutations. These
      residues were Asn-368 and Tyr-385, where substitutions that retained hydrogen
      bonding ability were preferred; Gly-376 and Gly-384, where only glycine was
      accepted; Phe-380, where a phenyl ring was preferred; and Met-386, where
      hydrophobic substitutions were preferred. Mutations that did not preserve these
      structural characteristics were highly detrimental to serotonin transport
      activity. These six residues form a stripe that runs at an angle down the side of
      the putative alpha-helix, lending support to this structural prediction.
      Mutations at some of these positions also specifically impaired transport
      activity under low Na+ conditions. Other mutations at nearby positions in
      transmembrane span 7 also impaired activity in low Na+, although the activity of
      the mutants in high Na+ was similar to wild type. These results suggest that at
      least some of the six critical residues play a role in Na+ binding or perhaps in
      the coupling of Na+ binding to later steps in the transport cycle. These residues
      may be important in other aspects of the transporter's function as well.

PMID- 9774429
TI  - Cell cycle- and Cln2p-Cdc28p-dependent phosphorylation of the yeast Ste20p
      protein kinase.
AB  - Ste20p from Saccharomyces cerevisiae is a member of the Ste20/p21-activated
      protein kinase family of protein kinases. The Ste20p kinase is post
      translationally modified by phosphorylation in a cell cycle-dependent manner, as
      judged by the appearance of phosphatase-sensitive species with reduced mobility
      on SDS-polyacrylamide gel electrophoresis. This modification is maximal during S
      phase, and correlates with the accumulation of Ste20p fused to green fluorescent
      protein at the site of bud emergence. Overexpression of Cln2p, but not Clb2p or
      Clb5p, causes a quantitative shift of Ste20p to the reduced mobility form, and
      this shift is dependent on Cdc28p activity. The post-translational mobility shift
      can be generated in vitro by incubation of Ste20p with immunoprecipitated Cln2p
      kinase complexes, but not by immunoprecipitated Clb2p or Clb5p kinase complexes.
      Ste20p is therefore a substrate for the Cdc28p kinase, and undergoes a Cln2p
      Cdc28p mediated mobility shift as cells initiate budding and DNA replication. In
      cells that express only the Cln2p G1 cyclin, minor overexpression of Ste20p
      causes aberrant morphology, suggesting a proper coordination of Ste20p and Cln
      Cdc28p activity may be required for the control of cell shape.

PMID- 9774430
TI  - Dermatan sulfate released after injury is a potent promoter of fibroblast growth
      factor-2 function.
AB  - Proteoglycans have been shown in vitro to bind multiple components of the
      cellular microenvironment that function during wound healing. To study the
      composition and function of these molecules when derived from an in vivo source,
      soluble proteoglycans released into human wound fluid were characterized and
      evaluated for influence on fibroblast growth factor-2 activity. Immunoblot
      analysis of wound fluid revealed the presence of syndecan-1, syndecan-4,
      glypican, decorin, perlecan, and versican. Sulfated glycosaminoglycan
      concentrations ranged from 15 to 65 microgram/ml, and treatment with
      chondroitinase B showed that a large proportion of the glycosaminoglycan was
      dermatan sulfate. The total glycosaminoglycan mixture present in wound fluid
      supported the ability of fibroblast growth factor-2 to signal cell proliferation.
      Dermatan sulfate, and not heparan sulfate, was the major contributor to this
      activity, and dermatan sulfate bound FGF-2 with Kd = 2.48 microM. These data
      demonstrate that proteoglycans released during wound repair are functionally
      active and provide the first evidence that dermatan sulfate is a potent mediator
      of fibroblast growth factor-2 responsiveness.

PMID- 9774431
TI  - Characterization of a novel branched tetrasaccharide of 3-deoxy-D-manno-oct-2
      ulopyranosonic acid. The structure of the carbohydrate backbone of the
      lipopolysaccharide from Acinetobacter baumannii strain nctc 10303 (atcc 17904).
AB  - For the first time, the tetrasaccharide Kdoalpha2-->5Kdoalpha2-->5(Kdoalpha2-
      >4)Kdo (Kdo is 3-deoxy-D-manno-oct-2-ulopyranosonic acid) has been identified in
      a bacterial lipopolysaccharide (LPS), i.e. in the core region of LPS from
      Acinetobacter baumannii NCTC 10303. The LPS was analyzed using compositional
      analysis, mass spectrometry, and NMR spectroscopy. The disaccharide D-GlcpNbeta1-
      >6D-GlcpN, phosphorylated at O-1 and O-4', was identified as the carbohydrate
      backbone of the lipid A. The Kdo tetrasaccharide is attached to O-6' of this
      disaccharide and is further substituted by short L-rhamnoglycans of varying
      length and by the disaccharide D-GlcpNAcalpha1-->4D-GlcpNA (GlcpNA, 2-amino-2
      deoxy-glucopyranosuronic acid). The core region is not substituted by phosphate
      residues and represents a novel core type of bacterial LPS. The complete
      carbohydrate backbone of the LPS is shown in Structure I as follows: where Rha is
      rhamnose. Except were indicated, monosaccharides possess the D-configuration.
      Sugars marked with an asterisk are present in non-stoichiometric amounts.

PMID- 9774432
TI  - Biosynthesis of pteridines. NMR studies on the reaction mechanisms of GTP
      cyclohydrolase I, pyruvoyltetrahydropterin synthase, and sepiapterin reductase.
AB  - GTP cyclohydrolase I catalyzes a ring expansion affording dihydroneopterin
      triphosphate from GTP. [1',2',3',4',5'-13C5, 2'-2H1]GTP was prepared
      enzymatically from [U-13C6]glucose for use as enzyme substrate. Multinuclear NMR
      experiments showed that the reaction catalyzed by GTP cyclohydrolase I involves
      the release of a proton from C-2' of GTP that is exchanged with the bulk solvent.
      Subsequently, a proton is reintroduced stereospecifically from the bulk solvent.
      This is in line with an Amadori rearrangement mechanism. The proton introduced
      from solvent occupies the pro-7R position in the enzyme product. The data also
      confirm that the reaction catalyzed by pyruvoyltetrahydropterin synthase results
      in the incorporation of solvent protons into positions C-6 and C-3' of the enzyme
      product. On the other hand, the reaction catalyzed by sepiapterin reductase does
      not involve any detectable incorporation of solvent protons into
      tetrahydrobiopterin.

PMID- 9774433
TI  - Roles of residues in mammalian mitochondrial elongation factor Ts in the
      interaction with mitochondrial and bacterial elongation factor Tu.
AB  - The crystal structure of the complex between Escherichia coli elongation factors
      Tu and Ts (EF-Tu.Ts) and subsequent mutagenesis work have provided insights into
      the roles of a number of residues in E. coli EF-Ts in its interaction with EF-Tu.
      The corresponding residues in bovine mitochondrial EF-Ts (EF-Tsmt) have been
      mutated. The abilities of the resulting EF-Tsmt derivatives to stimulate the
      activities of both E. coli and mitochondrial EF-Tu have been tested. Mutation of
      several residues in EF-Tsmt corresponding to amino acids important for the
      activity of E. coli EF-Ts has little or no effect on the activity of the
      mitochondrial factor, suggesting that these factors may use somewhat different
      mechanisms to promote guanine nucleotide exchange. In general, mutations that
      reduce the strength of the interaction between EF-Tsmt and E. coli EF-Tu increase
      the ability of EF-Tsmt to stimulate the activity of the bacterial factor. In
      contrast, these mutations tend to reduce the ability of EF-Tsmt to stimulate the
      activity of EF-Tumt. For example, F19A/I20A and H176A derivatives of EF-Tsmt are
      as active as E. coli EF-Ts in simulating E. coli EF-Tu. However, these mutations
      significantly decrease the ability of EF-Tsmt to stimulate EF-Tumt.

PMID- 9774434
TI  - The ferredoxin-dependent conversion of glyceraldehyde-3-phosphate in the
      hyperthermophilic archaeon Pyrococcus furiosus represents a novel site of
      glycolytic regulation.
AB  - The fermentative conversion of glucose in anaerobic hyperthermophilic Archaea is
      a variant of the classical Embden-Meyerhof pathway found in Bacteria and Eukarya.
      A major difference of the archaeal glycolytic pathway concerns the conversion of
      glyceraldehyde-3-phosphate. In the hyperthermophilic archaeon Pyrococcus
      furiosus, this reaction is catalyzed by an unique enzyme, glyceraldehyde-3
      phosphate ferredoxin oxidoreductase (GAPOR). Here, we report the isolation,
      characterization, and transcriptional analysis of the GAPOR-encoding gene. GAPOR
      is related to a family of ferredoxin-dependent tungsten enzymes in
      (hyper)thermophilic Archaea and, in addition, to a hypothetical protein in
      Escherichia coli. Electron paramagnetic resonance analysis of the purified P.
      furiosus GAPOR protein confirms the anticipated involvement of tungsten in
      catalysis. During glycolysis in P. furiosus, GAPOR gene expression is induced,
      whereas the activity of glyceraldehyde-3-phosphate dehydrogenase is repressed. It
      is discussed that this unprecedented unidirectional reaction couple in the
      pyrococcal glycolysis and gluconeogenesis gives rise to a novel site of
      glycolytic regulation that might be widespread among Archaea.

PMID- 9774435
TI  - Oncogenic Ha-Ras-dependent mitogen-activated protein kinase activity requires
      signaling through the epidermal growth factor receptor.
AB  - C3H10T1/2 fibroblasts transformed by the minimal expression of oncogenic Ha-Ras
      (V12H10 cells) or N-Ras (K61N10 cells) have constitutive mitogen-activated
      protein kinase (MAPK) activity and proliferate in serum-free medium. The
      constitutive MAPK activity and serum-independent proliferation of V12H10 cells
      are sensitive to the growth factor antagonist, suramin (Hamilton, M., and
      Wolfman, A. (1998) Oncogene 16, 1417-1428), suggesting that Ha-Ras-mediated
      regulation of the MAPK cascade is dependent upon the action of an autocrine
      factor. Serum-free medium conditioned by V12H10 cells contains an activity that
      stimulates MAPK activity in quiescent fibroblasts. This MAPK stimulatory activity
      could be specifically blocked by the epidermal growth factor receptor (EGFR)
      inhibitors, PD153035 and PD158780. These inhibitors also blocked the serum
      independent proliferation of V12H10 cells. Immunodepletion of conditioned medium
      with antibodies to transforming growth factor alpha and EGF significantly
      inhibited its ability to stimulate MAPK activity. Stable transfection of EGFR
      negative NR6 and EGFR-positive Swiss3T3 cells with oncogenic (G12V)Ha-Ras
      demonstrated that only the Ha-Ras-transfected Swiss 3T3 cells possessed
      constitutive MAPK activity, and this activity was sensitive to PD153035. These
      data suggest that autocrine activation of the EGFR is required for the regulation
      of the MAPK cascade in cells minimally expressing oncogenic Ha-Ras.

PMID- 9774436
TI  - A relationship between 5-lipoxygenase-activating protein and bcl-xL expression in
      murine pro-B lymphocytic FL5.12 cells.
AB  - Inhibitors of 5-lipoxygenase-activating protein (FLAP) have been found to induce
      apoptosis. The current study examined the expression of FLAP and bcl family
      proteins and the induction of apoptosis in interleukin-3-dependent control and
      bcl-xL-overexpressing FL5.12 cell lines after treatment with MK886, a specific
      FLAP inhibitor. FL5.12 cells contained a substantial amount of FLAP protein and
      mRNA but surprisingly had no measurable 5-lipoxygenase protein or 5-, 12-, or 15
      lipoxygenase activity. The basal level of FLAP protein in cells overexpressing
      bcl-xL was 70% less than in controls. FLAP disappeared 4 h after withdrawal of
      interleukin-3 in bcl-xL cells but not in control cells, which underwent
      apoptosis. A dose- and time-response study revealed that 5 nmol of MK886/10(6)
      cells was sufficient to induce apoptosis both in control and bcl-xL cells,
      respectively, but to different degrees. bcl-xL and bcl-2 proteins, but not bax or
      FLAP, were decreased by 4 h after 5 nmol of MK886/10(6) cells in both cell lines,
      although the higher levels of bcl-xL in overexpressors took longer to disappear.
      This early loss of bcl-xL and bcl-2 was not attributable to generalized
      proteolysis, as shown by Coomassie Blue staining and by the maintenance of bax.
      Caspase-3 was activated 2 h after MK886 treatment in control cells but not in bcl
      xL cells. Inhibition of caspase-3 decreased MK886-induced apoptosis by 50% in
      control cells. Inhibition of this caspase after MK886 treatment was unable to
      prevent the loss of bcl-xL in control cells but did provide partial protection
      for the loss of the transfected form, but not the endogenous form, in
      overexpressing cells. These data indicate that MK886 induces extensive apoptosis
      that is partially caspase-3 dependent and may be related to a rapid loss of bcl
      xL. Although caspase-3 inhibitors had no effect on the loss of bcl-xL, other
      caspases or protease systems may still be involved. The absence of 5-lipoxygenase
      in cells containing FLAP, the lower level of FLAP in bcl-xL cells, the apoptosis
      inducing activity of MK886, and the rapid loss of bcl-xL and bcl-2 proteins after
      treatment with MK886 strongly indicate that FLAP has activities unrelated to
      lipoxygenase and suggest a possible functional or regulatory link between these
      proteins, which share similar subcellular localizations.

PMID- 9774437
TI  - A 69-base pair fragment derived from human transcobalamin II promoter is
      sufficient for high bidirectional activity in the absence of a TATA box and an
      initiator element in transfected cells. Role of an E box in transcriptional
      activity.
AB  - A 69-base pair (bp) (-581/-513) fragment derived from human transcobalamin II
      distal promoter constructed upstream of a chloramphenicol acetyltransferase
      reporter gene demonstrated high bidirectional promoter activity in transfected
      epithelial Caco-2 cells. DNase I footprinting, gel mobility shift, supershift,
      and mutagenesis studies with the 69-bp fragment demonstrated that a GC box (-568/
      559) and an E box (-523/-528), which interacted with Sp1/Sp3 and USF1/USF2 (where
      USF is upstream stimulatory factor), respectively, were required for the full
      transcriptional activity of this fragment. Whereas mutations in the GC box
      reduced the promoter activity by 50%, mutations in the E box alone or in both the
      E box and GC box resulted in 90% loss of transcriptional activity. The essential
      role of the E box in the bidirectional promoter activity was further demonstrated
      by transient transfection in Caco-2, K-562, and HeLa cells using a 29-bp (-541/
      513) fragment that contained only the E box. Based on these results we suggest
      that 1) the E box is essential for both the GC box-dependent and -independent
      promoter activity of the 69-bp fragment, 2) cooperative interactions between
      Sp1/Sp3 and USFs are required for the full activation of the 69-bp promoter
      activity, and 3) the single E box is able to mediate bidirectional transcription
      in transfected cells in the absence of an obvious TATA box or a known initiator
      element.

PMID- 9774438
TI  - Branched-chain amino acids are essential in the regulation of PHAS-I and p70 S6
      kinase by pancreatic beta-cells. A possible role in protein translation and
      mitogenic signaling.
AB  - Amino acids have been identified as important signaling molecules involved in
      pancreatic beta-cell proliferation, although the cellular mechanism responsible
      for this effect is not well defined. We previously reported that amino acids are
      required for glucose or exogenous insulin to stimulate phosphorylation of PHAS-I
      (phosphorylated heat- and acid-stable protein regulated by insulin), a recently
      discovered regulator of translation initiation during cell mitogenesis. Here we
      demonstrate that essential amino acids, in particular branched-chain amino acids
      (leucine, valine, and isoleucine), are largely responsible for mediating this
      effect. The transamination product of leucine, alpha-ketoisocaproic acid, also
      stimulates PHAS-I phosphorylation although the transamination products of
      isoleucine and valine are ineffective. Since amino acids are secretagogues for
      insulin secretion by beta-cells, we investigated whether endogenous insulin
      secreted by beta-cells is involved. Interestingly, branched-chain amino acids
      stimulate phosphorylation of PHAS-I independent of endogenous insulin secretion
      since genistein (10 microM) and herbimycin A (1 microM), two tyrosine kinase
      inhibitors in the insulin signaling pathway, exert no effect on amino acid
      induced phosphorylation of PHAS-I. Furthermore, branched-chain amino acids retain
      their ability to induce phosphorylation of PHAS-I under conditions that block
      insulin secretion from beta-cells. In exploring the signaling pathway responsible
      for these effects, we find that rapamycin (25 nM) inhibits the ability of
      branched-chain amino acids to stimulate the phosphorylation of PHAS-I and p70(s6)
      kinase, suggesting that the mammalian target of rapamycin signaling pathway is
      involved. The branched-chain amino acid, leucine, also exerts similar effects on
      PHAS-I phosphorylation in isolated pancreatic islets. In addition, we find that
      amino acids are necessary for insulin-like growth factor (IGF-I) to stimulate the
      phosphorylation of PHAS-I indicating that a requirement for amino acids may be
      essential for other beta-cell growth factors in addition to insulin and IGF-I to
      activate this signaling pathway. We propose that amino acids, in particular
      branched-chain amino acids, may promote beta-cell proliferation either by
      stimulating phosphorylation of PHAS-I and p70(s6k) via the mammalian target of
      rapamycin pathway and/or by facilitating the proliferative effect mediated by
      growth factors such as insulin and IGF-I.

PMID- 9774439
TI  - Proteasomes regulate erythropoietin receptor and signal transducer and activator
      of transcription 5 (STAT5) activation. Possible involvement of the ubiquitinated
      Cis protein.
AB  - Cis is an Src homology 2 domain-containing protein, which binds to the
      erythropoietin receptor and decreases erythropoietin-stimulated cell
      proliferation. We show that Cis associates with the second tyrosine residue of
      the intracellular domain of the erythropoietin receptor (Tyr401). Two forms of
      Cis with molecular masses of 32 and 37 kDa were detected, and we demonstrate that
      the 37-kDa protein resulted from post-translational modifications of the 32-kDa
      form. Anti-ubiquitin antibodies recognized the 37-kDa form of Cis and the
      proteasome inhibitors N-acetyl-leucyl-leucyl-norleucinal and lactacystin
      inhibited its degradation, showing that the 37-kDa form of Cis is a ubiquitinated
      protein, which seems to be rapidly degraded by the proteasome. In erythropoietin
      stimulated UT-7 cells, the activation of the erythropoietin receptor and signal
      transducer and activator of transcription 5 (STAT5) was transient and returned to
      basal levels after 30-60 min of erythropoietin stimulation. In contrast, these
      proteins remained strongly phosphorylated, and STAT5 remained activated for at
      least 120 min in the presence of proteasome inhibitors. These experiments
      demonstrate that the proteasomes are involved in the down-regulation of the
      erythropoietin receptor activation signals. Because the proteasome inhibitors
      induced the accumulation of both the ubiquitinated form of Cis and the Cis
      erythropoietin receptor complexes, our results suggest that the ubiquitinated
      form of Cis could be involved in the proteasome-mediated inactivation of the
      erythropoietin receptor.

PMID- 9774440
TI  - Differential effects of PAK1-activating mutations reveal activity-dependent and 
      independent effects on cytoskeletal regulation.
AB  - PAKs are serine/threonine protein kinases that are activated by binding to Rac or
      Cdc42hs. Different forms of activated PAK1 have been reported to either promote
      membrane ruffling and focal adhesion assembly or cause focal adhesion disassembly
      and stress fiber dissolution. To understand the basis for these distinct
      morphological effects, we have examined the mechanism of mutational activation of
      PAK1, and characterized the effects of different active PAK1 proteins on
      cytoskeletal structure in vivo. We find that PAK1 contains an autoinhibitory
      domain that overlaps with its small G protein binding domain and that two
      separate activating mutations within this regulatory region each decrease
      autoinhibitory activity. Because only one of these mutations affects Cdc42hs
      binding activity, this indicates that activation of PAK1 by these mutations
      results from interference with the function of the autoinhibitory domain and not
      with small G protein binding activity. When we examined the morphological effects
      of these different forms of PAK1 in vivo, we found that PAK1 kinase activity was
      associated with disassembly of focal adhesions and actin stress fibers and that
      this may require interaction with potential SH3 domain-containing proteins.
      Lamellipodia formation and membrane ruffling caused by active PAK1 expression,
      however, was independent of PAK1 catalytic activity and likely requires
      interaction among multiple proteins binding to the PAK1 regulatory domain.

PMID- 9774441
TI  - Crystal structure of the catalytic domain of protein-tyrosine phosphatase SHP-1.
AB  - The crystal structures of the protein-tyrosine phosphatase SHP-1 catalytic domain
      and the complex it forms with the substrate analogue tungstate have been
      determined and refined to crystallographic R values of 0.209 at 2.5 A resolution
      and 0.207 at 2.8 A resolution, respectively. Despite low sequence similarity, the
      catalytic domain of SHP-1 shows high similarity in secondary and tertiary
      structures with other protein-tyrosine phosphatases (PTPs). In contrast to the
      conformational changes observed in the crystal structures of PTP1B and Yersinia
      PTP, the WPD loop (Trp419-Pro428) in the catalytic domain of SHP-1 moves away
      from the substrate binding pocket after binding the tungstate ion. Sequence
      alignment and structural analysis suggest that the residues in the WPD loop,
      especially the amino acid following Asp421, are critical for the movement of WPD
      loop on binding substrates and the specific activity of protein-tyrosine
      phosphatases. Our mutagenesis and kinetic measurements have supported this
      hypothesis.

PMID- 9774442
TI  - Molecular cloning of the oncofetal isoform of the human pancreatic bile salt
      dependent lipase.
AB  - Specific transcripts for bile salt-dependent lipase (BSDL), a 100-kDa
      glycoprotein secreted by the human pancreas, were immunodetected in BxPC-3 and
      SOJ-6 pancreatic tumoral cell lines. Sequencing of fragments, obtained by mRNA
      reverse transcription and amplification, confirmed the presence of BSDL
      transcripts in these cancer cells. The protein was detected in lysates of
      pancreatic tumoral cells, where it was mainly associated with membranes. Only a
      minute amount of the enzyme was detected in the culture media. Immunofluorescence
      studies demonstrated that in SOJ-6 cells, BSDL colocates with the p58 Golgi
      protein and suggested that the protein may be sequestrated within the Golgi
      compartment. These results demonstrated that BSDL is expressed in human
      pancreatic tumoral cells and cannot be secreted (or for the least very poorly).
      Subsequently, a cDNA covering the entire sequence of BSDL was obtained by reverse
      transcription-polymerase chain reaction. The sequence of this cDNA indicated that
      the N-terminal domain encoded by exons 1-10 was identical to that of BSDL
      expressed by the human normal pancreas. However, the sequence corresponding to
      exon 11, which should code for the 16 tandem-repeated identical mucin-like
      sequences of BSDL, was deleted by 330 base pairs (bp) and encoded only 6 of these
      repeated sequences. We conclude that this truncated variant of BSDL would be its
      oncofetal form, referred to as feto-acinar pancreatic protein. We then
      investigated whether the deletion of 330 bp affected the secretion of the
      protein. For this purpose, the cDNA corresponding to the mature form of the BSDL
      variant expressed in SOJ-6 cells was cloned into an expression/secretion vector
      and transfected into CHO-K1 cells. Results indicated that the variant of BSDL
      isolated from SOJ-6 cells was expressed and secreted by transfected cells.
      However, the level of BSDL secreted by these transfected CHO-K1 cells was
      significantly higher than that observed for SOJ-6 cells. Consequently, the
      retention of the oncofetal variant of BSDL observed in human pancreatic tumoral
      cells might not result from inherent properties of the protein.

PMID- 9774443
TI  - Identification of limiting steps for efficient trans-activation of HIV-1 promoter
      by Tat in Saccharomyces cerevisiae.
AB  - Cellular context is an important determinant for the activity of Tat, the trans
      activator of human immunodeficiency virus (HIV). We have investigated HIV-1
      promoter expression and trans-activation in Saccharomyces cerevisiae to provide
      clues about the limiting steps for Tat activity in this organism. A minimal 43
      nucleotide HIV promoter (HIV43) has the activity of a weak yeast promoter in the
      presence or absence of various enhancer binding sites (bs), whereas the entire
      long terminal repeat is not expressed. None of these constructs could be trans
      activated by Tat. Fusion proteins Gal4 binding domain (BD)-Tat48 and Gal4BD-Tat72
      are active with different efficiencies on various yeast promoters that have Gal4
      bs. They have 70 and 50% of Gal4 wild type activity on hybrid HIV promoters fused
      to Gal4 bs only in the presence of AP1 bs. This study shows that trans-activation
      of the HIV-1 promoter by Tat occurs in yeast when Tat is targeted to the promoter
      and a functional enhancer activity is present. Sp1 function and Tat transfer from
      the RNA to the promoter are two major elements for in vivo trans-activation of
      HIV-1 that are defective in S. cerevisiae but can be replaced by functional
      equivalents.

PMID- 9774444
TI  - Cloning the cDNA for a new human zinc finger protein defines a group of closely
      related Kruppel-like transcription factors.
AB  - We have identified a novel zinc finger protein that has been named ubiquitous
      Kruppel-like factor (UKLF) based on structural considerations and the pattern of
      gene expression. UKLF was isolated by the polymerase chain reaction approach
      using degenerate oligonucleotides corresponding to the DNA-binding domain of
      erythroid Kruppel-like factor (EKLF) and cDNA prepared from human vascular
      endothelial cells. The carboxyl-terminal portion of UKLF contains three zinc
      fingers of the Cys2-His2 type and binds in vitro to the CACCC motif of the beta
      globin promoter and to the Sp1 recognition sequence. The amino-terminal portion
      of UKLF consists of a hydrophobic region rich in serines and a negatively charged
      segment with several glutamic acid residues. The first 47 amino acids of the
      acidic region are nearly identical to the amino-terminal portion of another
      Kruppel-like factor, the so-called core promoter-binding protein (CPBP) or Zf9.
      Like CPBP/Zf9, UKLF can function as a transcription activator in co-transfection
      assays. However, this activity is lost when the highly conserved amino-terminal
      segment is deleted. These findings indicate that UKLF and CPBP/Zf9 represent a
      distinct subgroup of closely related Kruppel-like activators of transcription.
      Mapping of the UKLF gene to chromosome 2 suggested that UKLF and CPBP/Zf9
      translocated to different chromosomes following duplication from an ancestral
      gene.

PMID- 9774445
TI  - Heregulin regulates cytoskeletal reorganization and cell migration through the
      p21-activated kinase-1 via phosphatidylinositol-3 kinase.
AB  - The mechanisms through which heregulin (HRG) regulates the activities of breast
      cancer cells are currently unknown. We demonstrate that HRG stimulation of
      noninvasive breast cancer cells enhanced the conversion of globular to
      filamentous actin and the formation of membrane ruffles, stress fibers,
      filopodia, and lamellipodia and accompanied by increased cell migration. In
      addition, HRG triggered a rapid stimulation of p21-activated kinase1 (PAK1)
      activity and its redistribution into the leading edges of motile cells. The HRG
      induced stimulation of PAK1 kinase activity followed phosphatidylinositol-3
      kinase (PI-3 kinase) activation. Inhibition of PI-3 kinase activity blocked the
      activation of PAK1 kinase and also blocked cell migration in response to HRG.
      Furthermore, direct inhibition of PAK1 functions by the dominant-negative mutant
      suppressed the capacity of HRG to reorganize actin cytoskeleon structures. We
      also demonstrated that HRG stimulation promoted physical interactions between
      PAK1, actin, and human epidermal growth factor receptor 2 (HER2) receptors, and
      these interactions were dependent on the activation of PI-3 kinase. The blockade
      of HER2 receptor by an anti-HER2 monoclonal antibody resulted in the inhibition
      of HRG-mediated stimulation of PI-3 kinase/PAK pathway and also the formation of
      motile actin cytoskeleton structures but not extracellular signal-regulated
      kinases. These findings suggest a role of PI-3 kinase/PAK1-dependent
      reorganization of the cortical actin cytoskeleton in HRG-mediated increased cell
      migration, and these changes may have significant consequences leading to
      enhanced invasion by breast cancer cells.

PMID- 9774446
TI  - The H19 transcript is associated with polysomes and may regulate IGF2 expression
      in trans.
AB  - The imprinted H19 gene produces a fully processed transcript that does not
      exhibit any conserved open reading frame between mouse and man. Although
      transcriptional control elements associated with the mouse H19 locus have been
      shown to control the neighboring Igf2 gene in cis, the prevailing view is that
      the cytoplasmic H19 transcript does not display any function. In contrast to
      earlier reports, we show here that the H19 transcript is associated with
      polysomes in a variety of cell types, in both mouse and man. A possible trans
      function of the H19 gene is suggested by a reciprocal correlation in trans
      between cytoplasmic H19 and IGF2 mRNA levels, as well as IGF2 mRNA
      translatability. We discuss these results in terms of their challenge to the
      prevailing dogma on the function of the enigmatic H19 gene, as well as with
      respect to the ontogeny of the Beckwith-Wiedemann syndrome, and propose that the
      human H19 gene is an antagonist of IGF2 expressivity in trans.

PMID- 9774447
TI  - Paclitaxel (Taxol)-induced gene expression and cell death are both mediated by
      the activation of c-Jun NH2-terminal kinase (JNK/SAPK).
AB  - Paclitaxel (Taxol) is a novel anti-cancer drug that has shown efficacy toward
      several malignant tumors, particularly ovarian tumors. We reported previously
      that paclitaxel can induce interleukin (IL)-8 promoter activation in subgroups of
      ovarian cancer through the activation of both AP-1 and nuclear factor kappaB.
      Further analysis of paclitaxel analogs indicates that the degree of IL-8
      induction by analysis correlates with the extent of cell death; however, IL-8
      itself is not the cause of cell death. This suggests that pathways that lead to
      IL-8 and cell death may overlap, although IL-8 per se does not kill tumor cells.
      To decipher the upstream signals for paclitaxel-induced transcriptional
      activation and cell death, we studied the involvement of protein kinases that
      lead to the activation of AP-1, specifically the c-Jun NH2-terminal kinase
      (JNK1), p38, and the extracellular signal-regulated kinase 1 (ERK1). The role of
      IkappaB in paclitaxel-induced cell death was also analyzed. Paclitaxel activated
      JNK, and to a lesser degree p38, but not ERK1. Paclitaxel-induced IL-8 promoter
      activation was inhibited by dominant-inhibitory mutants of JNK, p38, and the
      super-repressor form of IkappaBalpha, but not by dominant-inhibitory forms of
      ERK1. Dominant-inhibitory mutants of JNK1 also greatly reduced paclitaxel-induced
      cell death, and the kinetics of JNK induction was closely followed by DNA
      fragmentation. These results indicate (i) that paclitaxel activates the JNK
      signaling pathway and (ii) that JNK activation is a common point of paclitaxel
      induced gene induction and cell death.

PMID- 9774448
TI  - Isolation of cholesterol-requiring mutant Chinese hamster ovary cells with
      defects in cleavage of sterol regulatory element-binding proteins at site 1.
AB  - The synthesis and uptake of cholesterol requires transcription factors designated
      sterol regulatory element-binding proteins (SREBPs). SREBPs are bound to
      membranes in a hairpin orientation with their transcriptionally active NH2
      terminal segments facing the cytosol. The NH2-terminal segments are released from
      membranes by two-step proteolysis initiated by site 1 protease (S1P), which
      cleaves in the luminal loop between two membrane-spanning segments. Next, site 2
      protease (S2P) releases the NH2-terminal fragment of SREBP. The S2P gene was
      recently isolated by complementation cloning using Chinese hamster ovary cells
      that require cholesterol for growth, due to a mutation in the S2P gene. A similar
      approach cannot be used for S1P because all previous cholesterol auxotrophs
      manifest defects in S2P, which is encoded by a single copy gene. To circumvent
      this problem, in the current studies we transfected Chinese hamster ovary cells
      with the S2P cDNA, assuring multiple copies. We mutagenized the cells, selected
      for cholesterol auxotrophy, and identified two mutant cell lines (SRD-12A and 
      12B) that fail to cleave SREBPs at site 1. Complementation analysis demonstrated
      that the defects in both cell lines are recessive and noncomplementing,
      indicating a mutation in the same gene. These cells should now be useful for
      expression cloning of the sterol-regulated S1P gene.

PMID- 9774449
TI  - Characterization of the high affinity cell-binding domain in the cell surface
      proteoglycan syndecan-4.
AB  - The syndecan family of cell surface proteoglycans regulates cell adhesion via
      their glycosaminoglycan chains and discrete domains of their core proteins. Core
      protein domains that are variable between syndecan family members may regulate
      syndecan-specific associations, thereby endowing individual syndecans with unique
      functions. A syndecan-4-specific domain has been identified in the extracellular
      syndecan-4 protein. This region mediates cell adhesion when provided as an
      artificial substratum and is localized within amino acids 56-109 of the
      recombinant extracellular protein domain of mouse syndecan-4 (mS4ED) (McFall, A.
      J., and Rapraeger, A. C. (1997) J. Biol. Chem. 272, 12901-12904). To characterize
      its interaction with the cell surface, radiolabeled ligand binding studies were
      performed. A single high affinity interaction, with a dissociation constant of 2
      x 10(-9) M, was observed between mS4ED and both human and mouse cells. Both
      chicken S4ED and mS4ED compete for this interaction, although they are only 34%
      identical within the cell-binding domain sequence. The extracellular protein
      domains of syndecan-1, -2, and -3, however, fail to compete. The interaction is
      also observed with native syndecan-4 shed from cell surfaces. Interestingly, the
      extracellular protein domain of syndecan-1 also mediates cell adhesion,
      suggesting a similar but discrete interaction for this family member.

PMID- 9774450
TI  - gamma-glutamyl leukotrienase, a gamma-glutamyl transpeptidase gene family member,
      is expressed primarily in spleen.
AB  - We have recently identified a mouse enzyme termed gamma-glutamyl leukotrienase
      (GGL) that converts leukotriene C4 (LTC4) to leukotriene D4 (LTD4). It also
      cleaves some other glutathione (GSH) conjugates, but not GSH itself (Carter, B.
      Z., Wiseman, A. L., Orkiszewski, R., Ballard, K. D., Ou, C.-N., and Lieberman, M.
      W. (1997) J. Biol. Chem. 272, 12305-12310). We have now cloned a full-length
      mouse cDNA coding for GGL activity and the corresponding gene. GGL and gamma
      glutamyl transpeptidase constitute a small gene family. The two cDNAs share a 57%
      nucleotide identity and 41% predicted amino acid sequence identity. Their
      corresponding genes have a similar intron-exon organization and are located 3
      kilobases apart. A search of Genbank and reverse transcription-polymerase chain
      reaction analysis failed to identify additional family members. Mapping of the
      GGL transcription start site revealed that the GGL promoter is TATA-less but
      contains an initiator, a control element for transcription initiation. Northern
      blots for GGL expression were negative. As judged by ribonuclease protection, in
      situ hybridization, and measurement of enzyme activity, spleen had the highest
      level of GGL expression. GGL is also expressed in thymic lymphocytes, bronchiolar
      epithelial cells, pulmonary interstitial cells, renal proximal convoluted tubular
      cells, and crypt cells of the small intestine as well as in cerebral, cerebellar,
      and brain stem neurons but not in glial cells. GGL is widely distributed in mice,
      suggesting an important role for this enzyme.

PMID- 9774451
TI  - Assessment of topogenic functions of anticipated transmembrane segments of human
      band 3.
AB  - Band 3 protein is a typical multispanning membrane protein whose membrane
      topology has been extensively studied from various protein chemical approaches.
      To clarify the membrane topogenesis of this multispanning protein on the
      endoplasmic reticulum, the topogenic functions of the anticipated transmembrane
      segments were individually assessed in an in vitro system using two series of
      model proteins in which each segment was placed in either a "stop-transfer"
      context or a "translocation initiation" context. They were expressed in a cell
      free system containing rough microsomal membranes, and their topologies were
      evaluated by taking advantage of either sensitivity to protease or accessibility
      to N-glycosylation. We found that some segments seem to possess insufficient
      topogenic functions for membrane integration: the second transmembrane segment
      (TM2) is insufficient for the stop-transfer sequence, and TM3, TM5, and TM7 are
      not sufficient for the translocation initiation. In contrast to these phenomena,
      we herein demonstrate that TM2 shows an efficient stop-transfer function when it
      is near the preceding TM1 and suggest that TM3, TM5, and TM7 are followed by TM
      segments with a strong topogenic function to form Nexo/Ccyt topology, via which
      the preceding segments are integrated into the membrane. From these results, we
      propose that the interactions between the TMs should be operative during membrane
      integration, and that the segments with a weak topogenic function are given a
      transmembrane orientation by their following TMs.

PMID- 9774452
TI  - The human RAD54 recombinational DNA repair protein is a double-stranded DNA
      dependent ATPase.
AB  - DNA double-strand break repair through the RAD52 homologous recombination pathway
      in the yeast Saccharomyces cerevisiae requires, among others, the RAD51, RAD52,
      and RAD54 genes. The biological importance of homologous recombination is
      underscored by the conservation of the RAD52 pathway from fungi to humans. The
      critical roles of the RAD52 group proteins in the early steps of recombination,
      the search for DNA homology and strand exchange, are now becoming apparent. Here,
      we report the purification of the human Rad54 protein. We showed that human Rad54
      has ATPase activity that is absolutely dependent on double-stranded DNA.
      Unexpectedly, the ATPase activity appeared not absolutely required for the DNA
      repair function of human Rad54 in vivo. Despite the presence of amino acid
      sequence motifs that are conserved in a large family of DNA helicases, no
      helicase activity of human Rad54 was observed on a variety of different DNA
      substrates. Possible functions of human Rad54 in homologous recombination that
      couple the energy gained from ATP hydrolysis to translocation along DNA, rather
      than disruption of base pairing, are discussed.

PMID- 9774453
TI  - Sites important for PLCbeta2 activation by the G protein betagamma subunit map to
      the sides of the beta propeller structure.
AB  - The betagamma subunits of the heterotrimeric GTP-binding proteins (G proteins)
      that couple heptahelical, plasma membrane-bound receptors to intracellular
      effector enzymes or ion channels directly regulate several types of effectors,
      including phospholipase Cbeta and adenylyl cyclase. The beta subunit is made up
      of two structurally different regions: an N-terminal alpha helix followed by a
      toroidal structure made up of 7 blades, each of which is a twisted beta sheet
      composed of four anti-parallel beta strands (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; Lambright, D. G., Sondek, J., Bohm, A., Skiba, N. P., Hamm,
      H. E., and Sigler, P. B. (1996) Nature 379, 311-319). We have previously shown
      that sites for activation of PLCbeta2, PLCbeta3, and adenylyl cyclase II overlap
      on the "top" surface of the propeller, where Galpha also binds (Li, Y.,
      Sternweis, P. M., Charnecki, S., Smith, T. F., Gilman, A. G., Neer, E. J., and
      Kozasa, T. (1998) J. Biol. Chem. 273, 16265-16272). The present study was
      undertaken to identify the regions on the side of the torus that might be
      important for effector interactions. We made mutations in each of the outer beta
      strands of the G protein beta1 propeller, as well as mutations in the loops that
      connect the outer strands to the adjacent beta strands. Our results suggest that
      activation of PLCbeta2 involves residues in the outer strands of blades 2, 6, and
      7 of the propeller. We tested three of the mutations that most severely affected
      PLCbeta2 activity against two forms of adenylyl cyclase (ACI and ACII). Both
      inhibition of ACI and activation of ACII were unaffected by these mutations,
      suggesting that if ACI and ACII contact the outer strands, the sites of contact
      are different from those for PLCbeta2. We propose that distinct sets of contacts
      along the sides of the propeller will define the specificity of the interaction
      of betagamma with effectors.

PMID- 9774454
TI  - Induction of murine macrophage growth by oxidized low density lipoprotein is
      mediated by granulocyte macrophage colony-stimulating factor.
AB  - We have examined whether certain secreted factor(s) is involved in oxidized low
      density lipoprotein (Ox-LDL)-induced murine macrophage growth. An antibody
      against granulocyte-macrophage colony-stimulating factor (GM-CSF) effectively
      inhibited Ox-LDL-induced macrophage growth by >80%. Ox-LDL as well as
      phospholipase A2-treated acetylated LDL enhanced mRNA levels and protein release
      of GM-CSF from macrophages, while neither acetylated LDL nor
      lysophosphatidylcholine (lyso-PC) showed such effects. The maximal induction of
      GM-CSF by Ox-LDL was noted at 4 h, followed by a time-dependent decrease to a
      basal level within 24 h. Ox-LDL-induced macrophage growth was inhibited by 75% by
      replacement of the culture medium at 24 h by a fresh medium containing the same
      concentration of Ox-LDL, when GM-CSF had already returned to the basal level.
      Thus, a cytokine(s) other than GM-CSF is also expected to participate in Ox-LDL
      induced macrophage growth in a later phase. The Ox-LDL-induced GM-CSF release was
      inhibited by calphostin C, a protein kinase C inhibitor, and was significantly
      reduced in macrophages from the knockout mice lacking class A, type I and type II
      macrophage scavenger receptors (MSR-AI/AII). These results taken together
      indicate that effective endocytosis of lyso-PC of Ox-LDL by macrophages through
      MSR-AI/AII and subsequent protein kinase C activation have led to GM-CSF release
      into the medium which may play a priming role in conjunction with other cytokines
      in Ox-LDL-induced macrophage growth.

PMID- 9774455
TI  - Modification of the E-cadherin-catenin complex in mitotic Madin-Darby canine
      kidney epithelial cells.
AB  - One of the hallmarks of polarized epithelial cells undergoing mitosis is their
      rounded morphology. This phenotype correlates with a reduced cell-substratum
      adhesion, apparently caused by a modulation of integrin function. However, it is
      still unclear whether the cadherin-mediated cell-cell adhesion is affected as
      well. To address this question, the cadherin complex was analyzed in different
      cell cycle stages of Madin-Darby canine kidney cells. By immunofluorescence,
      mitotic Madin-Darby canine kidney cells showed an increased staining of E
      cadherin and the catenins (alpha-catenin, beta-catenin, plakoglobin, p120(ctn))
      in the cytosol, suggesting a reorganization of the cadherin-catenin complex
      during mitosis. Biochemical analysis revealed that the overall amount of these
      components, as well as the proportion of the complex associated with the actin
      cytoskeleton, remained unchanged in mitotic cells. However, we found evidence for
      an internalization of E-cadherin during mitosis. In addition, the cadherin
      catenin complex was analyzed for mitosis-specific changes in phosphorylation. We
      report a decrease in the tyrosine phosphorylation of beta-catenin, plakoglobin,
      and p120(ctn) during mitosis. Moreover, we observed a mitosis-specific Ser/Thr
      phosphorylation of p120(ctn), as detected by the MPM-2 antibody. Hence, the
      cadherin/catenin complex is a target for different posttranslational
      modifications during mitosis, which may also have a profound impact on cadherin
      mediated cell-cell adhesion.

PMID- 9774456
TI  - Actin filaments facilitate insulin activation of the src and collagen
      homologous/mitogen-activated protein kinase pathway leading to DNA synthesis and
      c-fos expression.
AB  - The exact mechanism of the spatial organization of the insulin signaling pathway
      leading to nuclear events remains unknown. Here, we investigated the involvement
      of the actin cytoskeleton in propagation of insulin signaling events leading to
      DNA synthesis and expression of the immediate early genes c-fos and c-jun in L6
      muscle cells. Insulin reorganized the cellular actin network and increased the
      rate of DNA synthesis and the levels of c-fos mRNA, but not those of c-jun mRNA,
      in undifferentiated L6 myoblasts. Similarly, insulin markedly elevated the levels
      of c-fos mRNA but not of c-jun mRNA in differentiated L6 myotubes. Disassembly of
      the actin filaments by cytochalasin D, latrunculin B, or botulinum C2 toxin
      significantly inhibited insulin-mediated DNA synthesis in myoblasts and abolished
      stimulation of c-fos expression by the hormone in myoblasts and myotubes. Actin
      disassembly abolished insulin-induced phosphorylation and activation of
      extracellulor signal-regulated kinases, activation of a 65-kda member of the p21
      activated kinases, and phosphorylation of p38 mitogen-activated protein kinases
      but did not prevent activation of phosphatidylinositol 3-kinase and p70(S6k).
      Under these conditions, insulin-induced Ras activation was also abolished, and
      Grb2 association with the Src and collogen homologous (Shc) molecule was
      inhibited without inhibition of the tyrosine phosphorylation of Shc. We conclude
      that the actin filament network plays an essential role in insulin regulation of
      Shc-dependent signaling events governing gene expression by facilitating the
      interaction of Shc with Grb2.

PMID- 9774457
TI  - Recruitment and activation of SHP-1 protein-tyrosine phosphatase by human
      platelet endothelial cell adhesion molecule-1 (PECAM-1). Identification of
      immunoreceptor tyrosine-based inhibitory motif-like binding motifs and
      substrates.
AB  - Stimulation of platelet aggregation leads to tyrosine phosphorylation of a number
      of receptors and signaling molecules including platelet endothelial cell adhesion
      molecule-1 (PECAM-1). In this report, we demonstrate that both protein-tyrosine
      phosphatases SHP-1 and SHP-2 physically associate with different kinetics of
      assembly with tyrosine-phosphorylated human PECAM-1 during integrin alphaIIbbeta3
      mediated platelet aggregation. Peptido-precipitation analysis revealed that
      tyrosine-phosphorylated peptides encompassing residues 658-668 and 681-691 of
      PECAM-1 bound specifically to both protein-tyrosine phosphatases SHP-1 and SHP-2.
      We further show that the association of SHP-1 with PECAM-1 occurs through the
      direct interaction of the src homology region 2 domains of SHP-1 with two highly
      conserved phosphotyrosine binding motifs within PECAM-1 having the sequences
      NSDVQpY663TEVQV and DTETVpY686SEVRK (where pY represents phosphotyrosine). In
      vitro dephosphorylation experiments using phosphotyrosyl PECAM-1 peptides
      encompassing either Tyr-663 or Tyr-686 revealed induction of SHP-1 catalytic
      activity, suggesting that PECAM-1 serves as a SHP-1 substrate. Surface plasmon
      resonance studies reveal that recombinant SHP-2 binds PECAM-1 phosphopeptides
      with 5-fold higher affinity than recombinant SHP-1. These data suggest that in
      hematopoietic cells such as platelets, PECAM-1 cellular signaling is regulated by
      the selective recruitment and activation of two distinct protein-tyrosine
      phosphatases, SHP-1 and SHP-2, via a common immunoreceptor tyrosine-based
      inhibitory-like motif.

PMID- 9774458
TI  - Interaction of Bnr1p with a novel Src homology 3 domain-containing Hof1p.
      Implication in cytokinesis in Saccharomyces cerevisiae.
AB  - Proteins containing the formin homology (FH) domains FH1 and FH2 are involved in
      cytokinesis or establishment of cell polarity in a variety of organisms. We have
      shown that the FH proteins Bni1p and Bnr1p are potential targets of the Rho
      family small GTP-binding proteins and bind to an actin-binding protein, profilin,
      at their proline-rich FH1 domains to regulate reorganization of the actin
      cytoskeleton in the yeast Saccharomyces cerevisiae. We found here that a novel
      Src homology 3 (SH3) domain-containing protein, encoded by YMR032w, interacted
      with Bnr1p in a GTP-Rho4p-dependent manner through the FH1 domain of Bnr1p and
      the SH3 domain of Ymr032wp. Ymr032wp weakly bound to Bni1p. Ymr032wp was
      homologous to cdc15p, which is involved in cytokinesis in Schizosaccharomyces
      pombe, and we named this gene HOF1 (homolog of cdc 15). Both Bnr1p and Hof1p were
      localized at the bud neck, and both the bnr1 and hof1 mutations showed synthetic
      lethal interactions with the bni1 mutation. The hof1 mutant cells showed
      phenotypes similar to those of the septin mutants, indicating that HOF1 is
      involved in cytokinesis. These results indicate that Bnr1p directly interacts
      with Hof1p as well as with profilin to regulate cytoskeletal functions in S.
      cerevisiae.

PMID- 9774459
TI  - Phosphorylation of alphaB-crystallin in mitotic cells and identification of
      enzymatic activities responsible for phosphorylation.
AB  - The immunofluorescence localization of alphaB-crystallin in U373 MG human glioma
      cells with an antibody specific for alphaB-crystallin that had been
      phosphorylated at Ser-45 revealed an intense staining of cells in the mitotic
      phase of the cell cycle. Phosphorylated forms of alphaB-crystallin in mitotic
      cells were detected in all cell lines examined and in tissue sections of mouse
      embryos. Increases in the levels of alphaB-crystallin that had been
      phosphorylated at Ser-45 and Ser-19, but not at Ser-59, were detected
      biochemically by isoelectric focusing or SDS-polyacrylamide gel electrophoresis
      and a subsequent Western blot analysis of extracts of cells collected at the
      mitotic phase. When we estimated the phosphorylation activity specific for alphaB
      crystallin in extracts of mitotic U373 MG cells, using the amino-terminal 72
      amino acid peptide derived from unphosphorylated alphaB2-crystallin as the
      substrate, we found that the activities responsible for the phosphorylation of
      Ser-45 and Ser-19 were markedly enhanced but that the activity responsible for
      the phosphorylation of Ser-59 was suppressed. The protein kinases responsible for
      the phosphorylation of Ser-45 and Ser-59 in the amino-terminal 72-amino acid
      peptide were partially purified from extracts of cells that had been stimulated
      by exposure to H2O2 in the presence of calyculin A. The activities responsible
      for the phosphorylation of Ser-45 and Ser-59 were eluted separately from a column
      of Superdex 200 at fractions corresponding to about 40 and 60 kDa, respectively,
      while the kinase for Ser-19 was unstable. p44/42 mitogen-activated protein (MAP)
      kinase and MAP kinase-activated protein (MAPKAP) kinase-2 were concentrated in
      the Ser-45 kinase fraction and Ser-59 kinase fraction, respectively. Recombinant
      human p44 MAP kinase and MAPKAP kinase-2 purified from rabbit muscle selectively
      phosphorylated Ser-45 and -59, respectively. The Ser-45 kinase fraction and Ser
      59 kinase fraction phosphorylated myelin basic protein and hsp27, respectively.
      These results suggest that the phosphorylations of Ser-45 and Ser-59 in alphaB
      crystallin are catalyzed by p44/42 MAP kinase and MAPKAP kinase-2, respectively,
      in cells and that the phosphorylation of Ser-45 by p44/42 MAP kinase is enhanced
      while the phosphorylation of Ser-59 by MAPKAP kinase-2 is suppressed during cell
      division.

PMID- 9774461
TI  - Alzheimer's peptide Abeta1-42 binds to two beta-sheets of alpha1-antichymotrypsin
      and transforms it from inhibitor to substrate.
AB  - The serpin alpha1-antichymotrypsin is a major component of brain amyloid plaques
      in Alzheimer's disease. In vitro alpha1-antichymotrypsin interacts with the
      Alzheimer's amyloid peptide Abeta1-42 and stimulates both formation and
      disruption of neurotoxic Abeta1-42 fibrils in a concentration-dependent manner.
      We have constructed a new hybrid model of the complex between Abeta1-42 and
      alpha1-antichymotrypsin in which both amino and carboxyl sequences of Abeta1-42
      insert into two different beta-sheets of alpha1-antichymotrypsin. We have tested
      this model and shown experimentally that full-length and amino-terminal segments
      of Abeta1-42 bind to alpha1-antichymotrypsin as predicted. We also show that
      Abeta1-42 forms both intra- and intermolecular SDS-stable complexes with alpha1
      antichymotrypsin and that the binding of Abeta1-42 to alpha1-antichymotrypsin
      abolishes the inhibitory activity of the latter and its ability to form stable
      complex with chymotrypsin. The existence of both inter- as well as intramolecular
      complexes of Abeta1-42 explains the nonlinear concentration-dependent effects of
      alpha1-antichymotrypsin on Abeta1-42 fibril formation, which we have
      reinvestigated here over a broad range of Abeta1-42:alpha1-antichymotrypsin
      ratios. These data suggest a molecular basis for the distinction between
      amorphous and fibrillar Abeta1-42 in vivo. The reciprocal effects of Abeta1-42
      and alpha1-antichymotrypsin could play a role in the etiology of Alzheimer's
      disease.

PMID- 9774460
TI  - The TRAF family of signal transducers mediates NF-kappaB activation by the TRANCE
      receptor.
AB  - Tumor necrosis factor (TNF)-related activation-induced cytokine (TRANCE), a
      member of the TNF family expressed on activated T-cells, bone marrow stromal
      cells, and osteoblasts, regulates the function of dendritic cells (DC) and
      osteoclasts. The TRANCE receptor (TRANCE-R), recently identified as receptor
      activator of NF-kappabeta (RANK), activates NF-kappaB, a transcription factor
      critical in the differentiation and activation of those cells. In this report we
      identify the TNF receptor-associated factor (TRAF) family of signal transducers
      as important components of TRANCE-R-mediated NF-kappaB activation.
      Coimmunoprecipitation experiments suggested potential interactions between the
      cytoplasmic tail of TRANCE-R with TRAF1, TRAF2, TRAF3, TRAF5, and TRAF6. Dominant
      negative forms of TRAF2, TRAF5, and TRAF6 and an endogenous inhibitor of TRAF2,
      TRAF-interacting protein (TRIP), substantially inhibited TRANCE-R-mediated NF
      kappaB activation, suggesting a role of TRAFs in regulating DC and osteoclast
      function. Overexpression of combinations of TRAF dominant negative proteins
      revealed competition between TRAF proteins for the TRANCE-R and the possibility
      of a TRAF-independent NF-kappaB pathway. Analysis of TRANCE-R deletion mutants
      suggested that the TRAF2 and TRAF5 interaction sites were restricted to the C
      terminal 93 amino acids (C-region). TRAF6 also complexed to the C-region in
      addition to several regions N-terminal to the TRAF2 and TRAF5 association sites.
      Furthermore, transfection experiments with TRANCE-R deletion mutants revealed
      that multiple regions of the TRANCE-R can mediate NF-kappaB activation.

PMID- 9774462
TI  - Domains mediating intramolecular folding and oligomerization of MxA GTPase.
AB  - MxA is an interferon-induced GTPase of human cells that inhibits the
      multiplication of several RNA viruses by a still poorly understood mechanism.
      Previous biochemical studies indicated that the C terminus of MxA folds back to
      form a functional GTP-binding pocket, and that an internal fragment contains a
      domain required for oligomerization. Using the yeast two-hybrid system, we have
      now mapped these domains. MxA sequences located downstream of amino acid 564 were
      found to strongly interact with an internal domain that includes amino acids 372
      to 540. This interaction was abolished by mutating phenylalanine 382 or leucine
      612, which is part of a leucine zipper motif. Neither the C-terminal nor the
      internal MxA fragments formed homo-oligomers. Using a mammalian nuclear transport
      assay that can detect protein-protein interactions, we further found that full
      length MxA forms complexes with MxA fragments that include amino acids 372 to
      540. This interaction was not observed when phenylalanine 382 was exchanged for
      alanine or arginine. Furthermore, interaction of two full-length MxA molecules
      occurred only if at least one of them carried a functional C-terminal leucine
      zipper motif. These results suggest that C-terminal back-folding and
      oligomerization are two alternative outcomes of the same type of interaction
      between the C-terminal and the internal domains of MxA. Intramolecular
      interaction is believed to result in the formation of MxA monomers, whereas
      intermolecular interaction may induce the formation of large MxA oligomers.

PMID- 9774463
TI  - Different classes of coactivators recognize distinct but overlapping binding
      sites on the estrogen receptor ligand binding domain.
AB  - We have analyzed interaction of coactivators with the wild-type estrogen receptor
      alpha (ER), HEG0, and a mutant, L536P-HEG0, which is constitutively active in
      several transiently transfected cells and a HeLa line that stably propagates an
      estrogen-sensitive reporter gene. Different classes of coactivators do not
      recognize the ER ligand binding domain (LBD) in the same manner. Steroid receptor
      coactivator-1 (SRC-1), amplified in breast cancer-1 (AIB-1), transcriptional
      intermediary factor-1 (TIF-1), transcriptional intermediary factor-2 (TIF-2), and
      receptor interacting protein 140 (RIP140) interacted with HEG0 and L536P-HEG0 in
      the presence of estradiol, but generally not in the presence of anti-estrogens.
      However, ICI164,384 stimulated some interaction of RIP140 with LBDs. SRC-1, AIB
      1, and RIP140 interacted constitutively with the L536P ER, whereas TIF-1 and TIF
      2 interacted only weakly in the absence of hormone. Reciprocal competition for
      binding to the ER LBD was observed between different classes of coactivators.
      Moreover, coexpression of RIP140 blocked enhanced transactivation by HEG0
      observed in the presence of TIF-2, suggesting that RIP140 may play a negative
      role in ER signaling. We conclude that constitutive activity of L536P-HEG0 is
      manifested to similar degrees in different cell types and likely arises from
      constitutive coactivator binding; different classes of coactivators recognize
      distinct but overlapping binding sites on the ER LBD. Finally, the observation
      that L536P-HEG0 interacted constitutively with AIB-1, a coactivator that has been
      implicated in ER signaling in breast and ovarian cancer, suggests that similar
      mutations in the ER may contribute to hormone-independent proliferation of breast
      and ovarian cells.

PMID- 9774464
TI  - Oncogene-dependent regulation of caspase activation by p53 protein in a cell-free
      system.
AB  - The mechanism by which p53 modulates apoptosis in cancer therapy is incompletely
      understood. Here, cell-free extracts from irradiated tumor cells are described in
      which endogenous p53 protein is shown to participate in caspase activation. This
      apoptotic activity is also oncogene-dependent, but independent of transcription
      in general or the presence of Bax or cytochrome c. A general use for this system
      is as a cell-free screen for apoptosis modulators. In this way, profound effects
      of protein kinase A were identified and corroborated in vivo by the protection
      conferred by cAMP against diverse triggers of p53-dependent apoptosis. This
      system provides direct biochemical evidence that p53 protein can transduce
      apoptotic signals through protein-protein interactions and reveals a modulator
      kinase pathway capable of regulating p53-dependent caspase activation.

PMID- 9774465
TI  - The nature of human immunodeficiency virus type 1 strand transfers.
AB  - The diploid nature of human immunodeficiency virus type 1 (HIV-1) suggests that
      recombination serves a central function in virus replication and evolution. A
      system was developed to examine HIV-1 strand transfers, including the obligatory
      DNA primer strand transfers as well as recombinational crossovers during reverse
      transcription. Sequence heterogeneity between different strains of HIV-1 was
      exploited for examining primer transfer events. Both intra- and intermolecular
      primer transfers were observed at similar frequencies during minus-strand DNA
      synthesis, whereas primer transfers during plus-strand DNA synthesis were
      primarily intramolecular. Sequence analysis of long terminal repeats from progeny
      proviruses also revealed a high rate of homologous recombination during minus
      strand synthesis, corresponding to an overall rate of approximately three
      crossovers per HIV-1 genome per cycle of replication. These results imply that
      both viral genomic RNAs serve as templates during HIV-1 reverse transcription and
      that primer strand transfers and recombination may contribute substantially to
      the rapid genetic variation of HIV-1.

PMID- 9774466
TI  - Induction of thymocyte apoptosis by Ca2+-independent protein kinase C (nPKC)
      activation and its regulation by calcineurin activation.
AB  - Glucocorticoids appear to participate in apoptosis of unselected CD4(+)CD8(+)
      thymocytes. Activation of Ca2+-independent novel protein kinase C (nPKC) precedes
      glucocorticoid-induced thymocyte apoptosis, while proper levels of Ca2+-dependent
      protein kinase C (cPKC) and calcineurin activities contribute to rescue
      thymocytes. To clarify the role of nPKC in thymocyte apoptosis, murine thymocytes
      were stimulated with the diterpene diester, ingenol 3, 20-dibenzoate (IDB). IDB
      induced selective translocation of nPKC-delta, -epsilon, and -theta and PKC-mu
      from the cytosolic fraction to the particulate fraction and induced
      morphologically typical apoptosis through de novo synthesis of macromolecules.
      The apoptosis was also induced by thymeleatoxin, a diterpene ester, at relatively
      high concentrations that induced translocation of cPKC, nPKC-theta, and PKC-mu.
      The IDB- or thymeleatoxin-induced death was inhibited by non-isoform-selective
      PKC inhibitors, but not by their structural analogs with weak PKC-inhibitory
      activity or the selective inhibitor of cPKC and PKC-mu, Go 6976. The death was
      also inhibited by calcium ionophore ionomycin at concentrations within a narrow
      range. The range corresponded to the concentration range that contributes to the
      inhibition of glucocorticoid-induced apoptosis. The antiapoptotic effect was
      canceled by the immunosuppressant FK506 but not by rapamycin. These results
      indicate that activation of nPKC, especially nPKC-theta, induces apoptosis in
      thymocytes and that calcineurin activation regulates the apoptosis.

PMID- 9774467
TI  - Group II chaperonin in a thermophilic methanogen, Methanococcus
      thermolithotrophicus. Chaperone activity and filament-forming ability.
AB  - A gene encoding 544 amino acids for a subunit of group II chaperonin (thermosome)
      was cloned from a thermophilic methanogen, Methanococcus thermolithotrophicus.
      The deduced amino acid sequence showed 66.5, 56.1, and 20.1% similarities to
      those of Methanopyrus kandleri and Thermoplasma acidophilum and group I
      chaperonin of Escherichia coli, respectively. We call this chaperonin MTTS (M.
      thermolithotrophicus thermosome). The MTTS gene was expressed in E. coli. The
      purified recombinant MTTS seemed to be monomeric on gel filtration in the absence
      of Mg2+ and ATP. The monomer assembled to an oligomer (complex) in the presence
      of 50 mM MgCl2, 0.25 mM ATP, and 0.3 M (NH4)2SO4. It was eluted immediately
      before the elution volume of E. coli GroEL tetradecamer on gel filtration with a
      TSKgel G3000SWXL column. This reconstructed MTTS complex showed the cylindrical
      structure with two stacked rings in electron microscopy. The MTTS complex formed
      filamentous structures in the presence of Mg2+ and ATP at the protein
      concentration above 3.0 mg/ml. This filament formation was reversible. The MTTS
      filament was dissociated to the complex by dilution to the protein concentration
      of 0.2 mg/ml, even in the presence of Mg2+ and ATP. The MTTS complex exhibited
      weak ATPase activity with the hydrolysis rate of 74 mol of ATP hydrolysis/mol of
      MTTS complex/min at 70 degreesC. The MTTS complex promoted the refolding of
      chemically denatured thermophilic archaeal citrate synthase and glucose
      dehydrogenase at 50 degreesC in an ATP-dependent fashion. The analysis of
      nucleotide specificity of chaperone activity of MTTS suggested that it was
      coupled with hydrolysis of ATP, CTP, or UTP.

PMID- 9774468
TI  - Vitamin D-binding protein gene transcription is regulated by the relative
      abundance of hepatocyte nuclear factors 1alpha and 1beta.
AB  - Vitamin D-binding protein (DBP)/Gc-globulin, the major carrier of vitamin D and
      its metabolites in blood, is synthesized predominantly in the liver in a
      developmentally regulated fashion. By transient transfection analysis, we
      identified three regions in the 5'-flanking region of the rat DBP gene, segments
      F-2, B, and A, that contain tissue-specific transcriptional determinants. Gel
      mobility shift and DNase I footprinting analyses showed that all three regions
      contained binding sites for the hepatocyte nuclear factor 1 (HNF1), a
      transcriptional regulator composed of HNF1alpha and HNF1beta hetero- and
      homodimers. The activity of the most proximal segment A (coordinates -141 to -43)
      was DBP promoter-specific, position-dependent, and positively controlled by
      HNF1alpha. In contrast, the two more distal determinants (segments F-2 and B;
      coordinates -1844 to -1621 and -254 to -140, respectively) acted as classical
      enhancers in transfected hepatocyte-derived HepG2 cells; their activities were
      promoter- and orientation-independent, and disruption of their respective HNF1
      binding sites resulted in marked loss of DBP gene expression. Remarkably, the
      activities of these two distal elements depended upon the relative levels of
      HNF1alpha and HNF1beta; HNF1alpha had a major stimulatory effect, whereas
      HNF1beta acted as a trans-dominant inhibitor of HNF1alpha-mediated enhancer
      activity. These results suggested that the net expression of the DBP gene
      reflected a balance between the two major HNF1 species; the relative abundance of
      HNF1alpha and HNF1beta proteins in a cell may thus play a critical role in
      determining the pattern of gene expression.

PMID- 9774469
TI  - A cluster of basic repeats in the dystrophin rod domain binds F-actin through an
      electrostatic interaction.
AB  - The dystrophin rod domain is composed of 24 spectrin-like repeats and was thought
      to act mainly as a flexible spacer between the amino-terminal actin binding
      domain and carboxyl-terminal membrane-associated domains. We previously
      demonstrated that a fragment of the dystrophin rod domain also binds F-actin.
      However, the nature and extent of rod domain association with F-actin is
      presently unclear. To begin addressing these questions, we characterized two
      recombinant proteins representing adjacent regions of the dystrophin rod. DYS1416
      (amino acids 1416-1880) bound F-actin with a Kd of 14.2 +/- 5.2 microM and a
      stoichiometry of 1 mol:mol of actin. However, DYS1030 (amino acids 1030-1494)
      failed to bind F-actin, suggesting that not all rod domain repeats are capable of
      binding F-actin. Interestingly, DYS1416 corresponds to a unique region of the
      dystrophin rod rich in basic amino acids, whereas DYS1030 is composed mainly of
      acidic repeats. This observation suggested that DYS1416 may interact with acidic
      actin filaments through an electrostatic interaction. Supporting this hypothesis,
      actin binding by DYS1416 was dramatically inhibited by increasing ionic strength.
      We suggest that electrostatic interactions between basic spectrin-like repeats
      and actin filaments may contribute to the actin binding activity of other members
      of the actin cross-linking protein family.

PMID- 9774470
TI  - Substrate-directed function of calmodulin in autophosphorylation of
      Ca2+/calmodulin-dependent protein kinase II.
AB  - Autophosphorylation of Thr286 in Ca2+/calmodulin-dependent protein kinase II
      occurs within each holoenzyme by an intersubunit reaction and is essential for
      kinase function in vivo. In addition to a kinase-directed function of calmodulin
      to activate the kinase, a second calmodulin is required for the
      autophosphorylation of each Thr286 (Hanson, P. I., Meyer, T., Stryer, L., and
      Schulman, H. (1994) Neuron 12, 943-956). We have engineered heteromeric
      holoenzymes comprising distinct "kinase" and "substrate" subunits to test for
      kinase- and substrate-directed functions of calmodulin. The obligate kinase
      subunits have aspartate residues substituted for threonine at positions 286, 305,
      and 306 (the autophosphorylation and calmodulin-binding sites), making it
      constitutively active but unable to bind calmodulin. Obligate substrate subunits
      are catalytically inactive (K42M mutation) but are able to bind calmodulin.
      Phosphorylation of substrate subunits occurs specifically at Thr286 and is
      completely dependent upon the presence of calmodulin. Blocking the ability of the
      substrate subunit to bind calmodulin, either with inhibitor KN-93 or by
      mutagenesis of the calmodulin-binding domain of the substrate subunit, prevents
      its phosphorylation, consistent with a substrate-directed function of calmodulin
      that requires its direct binding to the subunit being phosphorylated.

PMID- 9774471
TI  - Carbonic anhydrase II binds to the carboxyl terminus of human band 3, the
      erythrocyte C1-/HCO3- exchanger.
AB  - In this study, we provide evidence that the 33-residue carboxyl-terminal (Ct)
      region of the human erythrocyte chloride/bicarbonate exchanger, band 3, binds
      carbonic anhydrase II (CAII). Immunofluorescence showed that tomato lectin
      mediated clustering of band 3 in ghost membranes caused a similar clustering of
      CAII, indicating an in situ association. CAII cosolubilized and
      coimmunoprecipitated with band 3, suggesting that the two proteins form a
      complex. Band 3 (K1/2 = 70 nM) or the membrane domain of band 3 (K1/2 = 100 nM)
      bound saturably to immobilized CAII in a solid phase binding assay. The
      interaction with CAII was specifically blocked by an antibody to the Ct of band
      3. Affinity blotting showed that a glutathione S-transferase (GST)-fusion protein
      (GST-Ct) containing the last 33 residues of human band 3 bound to CAII. The solid
      phase binding assay showed that binding of GST-Ct to immobilized CAII was
      saturable (K1/2 = 20 nM). The binding rate was slow (t1/2 = 12 h) at
      physiological ionic strength and pH but was enhanced at low ionic strength or
      acidic pH. Intact band 3 (Ki = 15 nM), the membrane domain of band 3 (Ki = 100
      nM), or antibodies to the Ct of band 3 were able to block GST-Ct binding to CAII,
      confirming the specificity of the interaction. Affinity chromatography showed
      that CAII bound to immobilized GST-Ct with a 1:1 stoichiometry. This work
      indicates that CAII, the bicarbonate supplier, is directly coupled to band 3, the
      chloride/bicarbonate exchanger in red blood cells.

PMID- 9774473
TI  - The DSD-1 carbohydrate epitope depends on sulfation, correlates with chondroitin
      sulfate D motifs, and is sufficient to promote neurite outgrowth.
AB  - The neural chondroitin sulfate (CS) proteoglycan (PG) DSD-1-PG was originally
      identified with the monoclonal antibody (mAb) 473HD. It promotes neurite
      outgrowth of hippocampal neurons when coated as a substrate in the presence of
      polycations. This effect is inhibited by mAb 473HD that specifically recognizes
      the DSD-1 epitope. The DSD-1 epitope is also detectable in CS-C and CS-D
      preparations from shark cartilage but not in other chondroitin sulfates that are
      structurally related and differ in their sulfation patterns. Non-sulfated DSD-1
      PG and chemically desulfated CS-D were not recognized by mAb 473HD, suggesting
      that the DSD-1 epitope depends on sulfation. It was possible to enrich DSD-1
      epitope-bearing carbohydrates and D disaccharide units from CS-C and CS-D
      preparations on a mAb 473HD affinity matrix. This indicates that the DSD-1
      epitope represents a distinct glycosaminoglycan structure containing D units. The
      analysis of glycosaminoglycan digestion products by high pressure liquid
      chromatography revealed that DSD-1-PG preparations contain a unique D
      disaccharide unit as well as an A, a C, and a non-sulfated disaccharide unit. In
      neurite outgrowth assays with hippocampal neurons, substrate-bound CS-D promoted
      neurite outgrowth, whereas CS-A, CS-B, or CS-C did not. This effect of CS-D was
      inhibited by mAb 473HD. DSD-1 epitope-enriched fractions obtained from CS-D and
      CS-C promoted neurite outgrowth, whereas CS-C had no such effect prior to
      enrichment on the mAb 473HD matrix. Based on these findings we conclude that the
      DSD-1 epitope by itself is sufficient to promote neurite outgrowth and that this
      activity is possibly associated with D motifs.

PMID- 9774472
TI  - Surfactant protein-D regulates surfactant phospholipid homeostasis in vivo.
AB  - Surfactant protein D (SP-D) is a 43-kDa member of the collectin family of
      collagenous lectin domain-containing proteins that is expressed in epithelial
      cells of the lung. The SP-D gene was targeted by homologous recombination in
      embryonic stem cells that were used to produce SP-D (+/-) and SP-D (-/-) mice.
      Both SP-D (-/-) and SP-D (+/-) mice survived normally in the perinatal and
      postnatal periods. Whereas no abnormalities were observed in SP-D (+/-) mice,
      alveolar and tissue phosphatidylcholine pool sizes were markedly increased in SP
      D (-/-) mice. Increased numbers of large foamy alveolar macrophages and enlarged
      alveoli were also observed in SP-D (-/-) mice. Phospholipid composition was
      unaltered in SP-D (-/-) mice, but surfactant morphology was abnormal, consisting
      of dense phospholipid membranous arrays with decreased tubular myelin. The
      pulmonary lipoidosis in the SP-D (-/-) mice was not associated with accumulation
      of surfactant proteins B or C, or their mRNAs, distinguishing the disorder from
      alveolar proteinosis syndromes. Surfactant protein A mRNA was reduced and, SP-A
      protein appeared to be reduced in SP-D (-/-) compared with wild type mice.
      Targeting of the mouse SP-D gene caused accumulation of surfactant lipid and
      altered phospholipid structures, demonstrating a previously unsuspected role for
      SP-D in surfactant lipid homeostasis in vivo.

PMID- 9774474
TI  - Protein kinase A stimulates binding of multiple proteins to a U-rich domain in
      the 3'-untranslated region of lactate dehydrogenase A mRNA that is required for
      the regulation of mRNA stability.
AB  - We have explored the molecular basis of the cAMP-induced stabilization of lactate
      dehydrogenase A (LDH-A) mRNA and identified four cytoplasmic proteins of 96, 67,
      52, and 50 kDa that specifically bind to a 30-nucleotide uridine-rich sequence in
      the LDH 3'-untranslated region with a predicted stem-loop structure. Mutational
      analysis revealed that specific protein binding is dependent upon an intact
      primary nucleotide sequence in the loop as well as integrity of the adjoining
      double-stranded stem structure, thus indicating a high degree of primary and
      secondary structure specificity. The critical stem-loop region is located between
      nucleotides 1473 and 1502 relative to the mRNA cap site and contains a previously
      identified cAMP-stabilizing region (CSR) required for LDH-A mRNA stability
      regulation by the protein kinase A pathway. The 3'-untranslated region binding
      activity of the proteins is up-regulated after protein kinase A activation,
      whereas protein dephosphorylation is associated with a loss of binding activity.
      These results imply a cause and effect relationship between LDH-A mRNA
      stabilization and CSR-phosphoprotein binding activity. We propose that the U-rich
      CSR is a recognition signal for CSR-binding proteins and for an mRNA processing
      pathway that specifically stabilizes LDH mRNA in response to activation of the
      protein kinase A signal transduction pathway.

PMID- 9774475
TI  - Distinct cytoplasmic regions of the prolactin receptor are required for prolactin
      induced calcium entry.
AB  - Two cytoplasmic regions of the prolactin (PRL) receptor are well documented for
      their participation in PRL signal transduction, the membrane proximal box 1 and
      the COOH-terminal region. In order to study the role of these regions in PRL
      induced Ca2+ increase, we use Chinese hamster ovary (CHO) cells stably
      transfected with mutated PRL receptor cDNA. These cells express the long form of
      PRL receptor deleted from box 1 (CHO Delta1 cells) or the 141 amino acids of the
      COOH-terminal region (CHO H3 cells). The patch-clamp technique in "whole-cell"
      configuration and microfluorimetric techniques were used singly or in
      combination. Data obtained for these cells were compared with those we have
      recently published using CHO cells expressing the wild-type long form of the PRL
      receptor (CHO TSE32). In contrast to CHO TSE32 cells, exposure of CHO Delta1 or
      H3 cells to PRL (0.05-50 nM) did not modify [Ca2+]i. We have previously shown
      that the PRL-induced calcium influx via voltage-insensitive, Ca2+ channels was
      due to the activation of tyrosine kinase-dependent K+ channels that hyperpolarize
      the CHO TSE32 cell membrane (hyperpolarization-driven Ca2+ influx). Therefore,
      two events are involved in PRL-induced Ca2+ changes (i) JAK2-activation of K+
      channels and (ii) intracellular messenger-opening of Ca2+ channels. In CHO Delta1
      cells, PRL (0.05-50 nM) neither hyperpolarized the membrane potential nor
      stimulated the JAK2-dependent K+ current, confirming the pivotal role played by
      box 1/JAK2 in the PRL-induced activation of K+ channels. However, when these
      cells were voltage-clamped below the resting membrane potential, application of 5
      nM PRL resulted in an increase in Ca2+ influx. Therefore, box 1/JAK2 was not
      involved in the opening of these Ca2+ channels. In CHO H3 cells, 5 nM PRL
      activated the K+ current and hyperpolarized the membrane potential without any
      effect on [Ca2+]i. Moreover, PRL was also ineffective on CHO H3 cells voltage
      clamped below the resting membrane potential. Therefore, the COOH-terminal region
      is involved in the production of the intracellular messenger that opens voltage
      independent Ca2+ channels. We conclude from these findings that box 1 and COOH
      terminal regions are both needed for PRL-induced Ca2+ changes.

PMID- 9774477
TI  - Association of GAP-43 with detergent-resistant membranes requires two
      palmitoylated cysteine residues.
AB  - GAP-43 is an abundant protein in axonal growth cones of developing and
      regenerating neurons. We found that GAP-43 was enriched in detergent-resistant
      membranes (DRMs) isolated by Triton X-100 extraction from PC12 pheochromocytoma
      cells and could be detected in detergent-insoluble plasma membrane remnants after
      extraction of cells in situ. GAP-43 is palmitoylated at Cys-3 and Cys-4. Mutation
      of either Cys residue prevented association with DRMs. A hybrid protein
      containing the first 20 amino acid residues of GAP-43 fused to beta-galactosidase
      was targeted to DRMs even more efficiently than GAP-43 itself. We conclude that
      tandem palmitoylated Cys residues can target GAP-43 to DRMs, defining a new
      signal for DRM targeting. We propose that tandem or closely spaced saturated
      fatty acyl chains partition into domains or "rafts" in the liquid-ordered phase,
      or a phase with similar properties, in cell membranes. These rafts are isolated
      as DRMs after detergent extraction. The brain-specific heterotrimeric G protein
      Go, which may be regulated by GAP-43 in vitro, was also enriched in DRMs from
      PC12 cells. Targeting of GAP-43 to rafts may function to facilitate signaling
      through Go. In addition, raft association may aid in sorting of GAP-43 into
      axonally directed vesicles in the trans-Golgi network.

PMID- 9774476
TI  - Cardiac-specific overexpression of mouse cardiac calsequestrin is associated with
      depressed cardiovascular function and hypertrophy in transgenic mice.
AB  - Calsequestrin is a high capacity Ca2+-binding protein in the sarcoplasmic
      reticulum (SR) lumen. To elucidate the functional role of calsequestrin in vivo,
      transgenic mice were generated that overexpressed mouse cardiac calsequestrin in
      the heart. Overexpression (20-fold) of calsequestrin was associated with cardiac
      hypertrophy and induction of a fetal gene expression program. Isolated transgenic
      cardiomyocytes exhibited diminished shortening fraction (46%), shortening rate
      (60%), and relengthening rate (60%). The Ca2+ transient amplitude was also
      depressed (45%), although the SR Ca2+ storage capacity was augmented, as
      suggested by caffeine application studies. These alterations were associated with
      a decrease in L-type Ca2+ current density and prolongation of this channel's
      inactivation kinetics without changes in Na+-Ca2+ exchanger current density.
      Furthermore, there were increases in protein levels of SR Ca2+-ATPase,
      phospholamban, and calreticulin and decreases in FKBP12, without alterations in
      ryanodine receptor, junctin, and triadin levels in transgenic hearts. Left
      ventricular function analysis in Langendorff perfused hearts and closed-chest
      anesthetized mice also indicated depressed rates of contraction and relaxation of
      transgenic hearts. These findings suggest that calsequestrin overexpression is
      associated with increases in SR Ca2+ capacity, but decreases in Ca2+-induced SR
      Ca2+ release, leading to depressed contractility in the mammalian heart.

PMID- 9774478
TI  - Splicing of 5' introns dictates alternative splice selection of
      acetylcholinesterase pre-mRNA and specific expression during myogenesis.
AB  - Splicing of alternative exon 6 to invariant exons 2, 3, and 4 in
      acetylcholinesterase (AChE) pre-mRNA results in expression of the prevailing
      enzyme species in the nervous system and at the neuromuscular junction of
      skeletal muscle. The structural determinants controlling splice selection are
      examined in differentiating C2-C12 muscle cells by selective intron deletion from
      and site-directed mutagenesis in the Ache gene. Transfection of a plasmid lacking
      two invariant introns (introns II and III) within the open reading frame of the
      Ache gene, located 5' of the alternative splice region, resulted in alternatively
      spliced mRNAs encoding enzyme forms not found endogenously in myotubes. Retention
      of either intron II or III is sufficient to control the tissue-specific pre-mRNA
      splicing pattern prevalent in situ. Further deletions and branch point mutations
      revealed that upstream splicing, but not the secondary structure of AChE pre
      mRNA, is the determining factor in the splice selection. In addition, deletion of
      the alternative intron between the splice donor site and alternative acceptor
      sites resulted in aberrant upstream splicing. Thus, selective splicing of AChE
      pre-mRNA during myogenesis occurs in an ordered recognition sequence in which the
      alternative intron influences the fidelity of correct upstream splicing, which,
      in turn, determines the downstream splice selection of alternative exons.

PMID- 9774479
TI  - Role of C-terminal serines in desensitization and phosphorylation of the mouse
      thromboxane receptor.
AB  - To investigate the role of C-terminal hydroxyamino acids in desensitization of
      the receptor for thromboxane A2 (TxA2), we created a mutant TxA2 receptor (TP
      receptor) in which serines at positions 321, 322, and 328 were replaced with
      either alanine or glycine. Mutant and wild type receptors were expressed in a
      mesangial cell line, and clones expressing similar numbers of receptors were
      studied. Affinity and specificity of TxA2 binding to the mutant receptor were
      identical to wild type receptors. In contrast, TxA2-induced inositol
      trisphosphate generation by the mutant receptor was enhanced compared with the
      wild type. Prior treatment with the TxA2 agonist U46619 reduced subsequent U46619
      induced increases in inositol trisphosphate generation by both receptors;
      however, the extent of desensitization was significantly reduced in the receptor
      mutant. Protein kinase C (PKC) inhibitors attenuated TxA2-induced desensitization
      of wild type receptors, but had little effect on TxA2-induced desensitization of
      mutant receptors. Pretreatment with the phorbol ester phorbol 12, 13-dybutyrate
      (PDBu) (100 nM) decreased subsequent responsiveness of wild type but not mutant
      TP receptors. -induced desensitization of wild type receptors was associated with
      enhanced phosphorylation of receptor proteins. This agonist-specific
      phosphorylation of the TP receptor was largely prevented by inhibitors of PKC.
      Treatment with 100 nM PDBu increased phosphorylation of both wild type and mutant
      TP receptors, but the extent of phosphorylation of the receptor mutant was
      reduced compared with the wild type. Increasing the concentration of PDBu from
      100 nM to 1 microM PDBu reduced responsiveness of both mutant and wild type
      receptors without enhancing phosphorylation of either of the receptor proteins.
      These data suggest that 1) phosphorylation of C-terminal serines contributes to
      agonist-specific desensitization of the TP receptor, 2) PKC-induced
      desensitization of TP receptors is caused, in part, by phosphorylation of C
      terminal serines, and 3) desensitization of TP receptors by PKC is complex and
      involves mechanisms that may not require direct phosphorylation of receptor
      proteins.

PMID- 9774480
TI  - The pipsqueak protein of Drosophila melanogaster binds to GAGA sequences through
      a novel DNA-binding domain.
AB  - Pipsqueak (Psq) belongs to a family of proteins defined by a phylogenetically old
      protein-protein interaction motif. Like the GAGA factor and other members of this
      family, Psq is an important developmental regulator in Drosophila, having
      pleiotropic functions during oogenesis, embryonic pattern formation, and adult
      development. The GAGA factor controls the transcriptional activation of homeotic
      genes and other genes by binding to control elements containing the GAGAG
      consensus motif. Binding is associated with formation of an open chromatin
      structure that makes the control regions accessible to transcriptional
      activators. We show here that Psq contains a novel DNA-binding domain, which
      binds, like the GAGA factor zinc finger DNA-binding domain, to target sites
      containing the GAGAG consensus motif. Binding is suppressed, as in the GAGA
      factor and other proteins of the family, by the associated protein-protein
      interaction motif. The DNA-binding domain, which we call the Psq domain, is
      identical with a previously identified region consisting of four tandem repeats
      of a conserved 50-amino acid sequence, the Psq motif. The Psq domain seems to be
      structurally related to known DNA-binding domains, both in its repetitive
      character and in the putative three-alpha-helix structure of the Psq motif, but
      it lacks the conserved sequence signatures of the classical eukaryotic DNA
      binding motifs. Psq may thus represent the prototype of a new family of DNA
      binding proteins.

PMID- 9774481
TI  - Increased oxidative damage is correlated to altered mitochondrial function in
      heterozygous manganese superoxide dismutase knockout mice.
AB  - This study characterizes mitochondria isolated from livers of Sod2(-/+) and
      Sod2(+/+) mice. A 50% decrease in manganese superoxide dismutase (MnSOD) activity
      was observed in mitochondria isolated from Sod2(-/+) mice compared with Sod2(+/+)
      mice, with no change in the activities of either glutathione peroxidase or
      copper/zinc superoxide dismutase. However, the level of total glutathione was 30%
      less in liver mitochondria of the Sod2(-/+) mice. The reduction in MnSOD activity
      in Sod2(-/+) mice was correlated to an increase in oxidative damage to
      mitochondria: decreased activities of the Fe-S proteins (aconitase and NADH
      oxidoreductase), increased carbonyl groups in proteins, and increased levels of 8
      hydroxydeoxyguanosine in mitochondrial DNA. In contrast, there were no
      significant changes in oxidative damage in the cytosolic proteins or nuclear DNA.
      The increase in oxidative damage in mitochondria was correlated to altered
      mitochondrial function. A significant decrease in the respiratory control ratio
      was observed in mitochondria isolated from Sod2(-/+) mice compared with Sod2(+/+)
      mice for substrates metabolized by complexes I, II, and III. In addition,
      mitochondria isolated from Sod2(-/+) mice showed an increased rate of induction
      of the permeability transition. Therefore, this study provides direct evidence
      correlating reduced MnSOD activity in vivo to increased oxidative damage in
      mitochondria and alterations in mitochondrial function.

PMID- 9774482
TI  - Carboxyl methylation of deamidated calmodulin increases its stability in Xenopus
      oocyte cytoplasm. Implications for protein repair.
AB  - The widely distributed protein-L-isoaspartate(D-aspartate) O-methyltransferase
      (PIMT; EC 2.1.1.77) is postulated to play a role in the repair or metabolism of
      damaged cellular proteins containing L-isoaspartyl residues derived primarily
      from the spontaneous deamidation of protein asparaginyl residues. To evaluate the
      functional consequence of PIMT-catalyzed methylation on the stability of
      isoaspartyl-containing proteins in cells, Xenopus laevis oocytes were
      microinjected with both deamidated and nondeamidated forms of recombinant chicken
      calmodulin (CaM) containing a hemagglutinin (HA) epitope at its N terminus.
      Processing of HA-CaM was monitored by electrophoretic analysis and Western
      blotting of oocyte extracts. The experiments indicate that deamidated HA-CaM is
      degraded after microinjection, while nondeamidated HA-CaM is stable. Kinetic
      analysis is consistent with the entry of microinjected HA-CaM into two
      intracellular pools with distinct hydrolytic stabilities. The larger, more stable
      pool may consist of HA-CaM bound to the heterogeneous pool of oocyte CaM binding
      proteins detected by an overlay procedure. Enzymatic methylation of deamidated HA
      CaM with purified PIMT prior to injection results in its stabilization.
      Conversely, inhibition of endogenous oocyte PIMT with sinefungin, a
      nonhydrolyzable analog of S-adenosylhomocysteine, increases the rate of
      deamidated HA-CaM degradation. These results are consistent with a role for PIMT
      catalyzed methylation in the repair of damaged cellular proteins.

PMID- 9774483
TI  - Differential and cooperative polysialylation of the neural cell adhesion molecule
      by two polysialyltransferases, PST and STX.
AB  - PST and STX are polysialyltransferases that form polysialic acid in the neural
      cell adhesion molecule (NCAM), and these two polysialyltransferases often exist
      together in the same tissues. To determine the individual and combined roles of
      PST and STX in polysialic acid synthesis, in the present study we asked if PST
      and STX differ in the acceptor requirement and if PST and STX act together in
      polysialylation of NCAM. We first examined whether PST and STX differ in the
      requirement of sialic acid and core structures of N-glycans attached to NCAM.
      Polysialic acid was formed well on Lec4 and Lec13 cells, which are defective in N
      acetylglucosaminyltransferase V and GDP-fucose synthesis, respectively,
      demonstrating that a side chain elongating from GlcNAcbeta1-->6Manalpha1-->6R and
      alpha-1,6-linked fucose are not required. PST and STX were found to add
      polysialic acid on NCAM.Fc molecules sialylated by alpha-2,3- or alpha-2,6
      linkage in vitro, but not on NCAM.Fc lacking either sialic acid. These results
      indicate that both PST and STX have relatively broad specificity on N-glycan core
      structures in NCAM and no remarkable difference exists between PST and STX for
      the requirement of core structures and sialic acid attached to the N-glycans of
      NCAM. We then, using various N-glycosylation site mutants of NCAM, discovered
      that PST strongly prefer the sixth N-glycosylation site, which is the closest to
      the transmembrane domain, over the fifth site. STX slightly prefer the sixth N
      glycosylation site over the fifth N-glycosylation site. The results also
      demonstrated that polysialic acid synthesized by PST is larger than that
      synthesized by STX in vitro. Moreover, a mixture of PST and STX more efficiently
      synthesized polysialic acid on NCAM than PST or STX alone. These results suggest
      that polysialylation of NCAM is influenced by the difference between PST and STX
      in their preference for N-glycosylation sites on NCAM. The results also suggest
      that PST and STX form polysialylated NCAM in a synergistic manner.

PMID- 9774485
TI  - In memoriam 

PMID- 9774484
TI  - UGA codon position affects the efficiency of selenocysteine incorporation into
      glutathione peroxidase-1.
AB  - A UGA codon and a selenocysteine insertion sequence in the 3'-untranslated region
      are the only established mRNA elements necessary for selenocysteine (Sec or U)
      incorporation during translation. These two elements, however, do not universally
      confer efficient Sec incorporation. The objective of this study was to
      systematically examine the effect of UGA codon position on efficiency of Sec
      insertion. In a glutathione peroxidase-1 (F-GPX1) expression vector, the UGA at
      the native position (U47) was mutated to a cysteine codon, and codons for Ser-7,
      Ser-12, Ser-18, Ser-29, Ser-45, Ser-93, Cys-154, Val-172, Ser-178, and Ser-195
      were individually mutated to UGA and transiently expressed in COS-7 cells. 75Se
      incorporation at the 11 positions was 31, 72, 54, 105, 90, 100, 146, 135, 13, 11,
      and 43%, respectively, of 75Se incorporation at U47, suggesting that Sec is more
      efficiently incorporated at UGA codons positioned in the middle of the coding
      region rather than close to the 5' or 3' ends. Ribonuclease protection showed
      that these differences were not due to differences in mRNA level. When the green
      fluorescence protein (GFP) coding region was placed in-frame at the 5' or 3' ends
      of the coding region in F-GPX1 to produce chimeric 50-51-kDa GFP/GPX1 proteins,
      Sec incorporation at UGA codons, formerly close to the 5' or 3' ends, was
      increased to levels comparable to the UGA at U47. Insertion of GFP after the UAA
      stop was just as effective in increasing Sec insertion efficiency as GFP inserted
      before the stop. These studies used a recombinant expression model that
      incorporated Sec at non-native UGA codons at rates equal to those of endogenous
      glutathione peroxidase-1 and showed that the efficiency of Sec incorporation can
      be modulated by UGA position; Sec incorporation at high efficiency appears to
      require that the UGA be >21 nucleotides from the AUG-start and >204 nucleotides
      from the selenocysteine insertion sequence element.

PMID- 9774486
TI  - Response to nimodipine in caffeine-induced neurotoxicity in cerebellar granular
      cell culture of rat pups.
AB  - Methylxanthines (theophylline, theobromine and caffeine) are widely used as
      central nervous system stimulants and caffeine is used in the treatment of apnea
      in newborns. Plasma therapeutic concentration of caffeine is around 110 microM.
      Caffeine diffuses the blood brain barrier easily, increasing oxygen consumption
      in neurones and leading to cell death. In the present study, 4-7-day-old rats
      were used to obtain cerebellar granular cell cultures. Caffeine was used 50, 150,
      250 and 350 microM concentrations and the most toxic dose for it was found to be
      350 microM. Death cell scores were 0.9+/-0.63 for control, 1.1+/-0.63 for 50
      microM, 0.89+/-0.47 for 150 microM (P>0.05 for both), 3.84+/-0.8 for 250 microM
      (P=0.024) and 6.2+/-0. 86 for 350 microM (P=0.001) caffeine concentrations. The
      role of voltage-dependent calcium channels in caffeine-induced neurotoxicity was
      tested with the doses of 100 and 200 microM nimodipine 45 min before or after the
      350 microM caffeine. Both doses of nimodipine after caffeine administration were
      found to be ineffective in blocking neurotoxicity. Doses administered 45 min
      prior to caffeine, reduced death cell score to 0.89+/-0.23 (P=0.000) for 100
      microM nimodipine and 2.35+/-0.96 (P=0.000) for 200 microM nimodipine
      administration into the cultures. A dose-dependent manner of nimodipine in
      ischemic states is well-known. In the light of these results, nimodipine may be
      used in the treatment of newborn apneas together with caffeine to prevent
      neurotoxic side effects of high or repeated doses of it.

PMID- 9774487
TI  - The analgesic effects of tryptophan and its metabolites in the rat.
AB  - Male Sprague-Dawley rats weighing 150-200 g were given doses of tryptophan methyl
      ester or its metabolites; kynurenine sulphate, kynurenic acid, xanthurenic acid,
      quinolinic acid, anthranilic acid methyl ester or picolinic acid methyl ester.
      Doses administered intraperitoneally were 50, 100, 200, 300, 400 and 600 mg kg-1.
      Pain sensitivity was assessed using the hotplate and tailflick methods at 30 min
      before and at 30-min interval after the injection of test compounds. The
      administrations of tryptophan, kynurenic acid, quinolinic acid, anthranilic acid,
      xanthurenic acid, picolinic acid, and kynurenine were associated with analgesia.
      Animals given 300 or 600 mg kg-1 of tryptophan exhibited a significant decrease
      (P<0.05; P<0.01, respectively) in pain sensitivity with the hotplate test. l
      Kynurenic acid (300 mg kg-1) produced analgesia (P<0.01) 30 min after drug
      administration. Quinolinic and anthranilic acids both produced prolonged decrease
      in pain sensitivity (P<0.05) using the tailflick test. These results indicate
      that tryptophan and some of its metabolites possess analgesic properties.

PMID- 9774488
TI  - Effects of lesions of the Substantia Innominata/Ventral Pallidum, globus pallidus
      and medial septum on rat's performance in object-recognition and radial-maze
      tasks: physostigmine and amphetamine treatments.
AB  - The present study examined the effects of electrolytic lesions of the Medial
      Septum/Vertical Diagonal Band of Broca (MS/VDBB), the Globus Pallidus (GP) and
      the Substantia- Innominata/Ventral Pallidum (SI/VP) on the performance of rats in
      object-recognition memory and radial-maze learning tests. In the latter test,
      subgroups of sham-operated, MS/VDBB, SI/VP and GP rats were treated with saline,
      amphetamine or physostigmine. (1) In the object recognition task, the level of
      discrimination wa s significantly lower in GP compared to SI/VP and in both GP
      and SI/VP compared to Control and MS/VDBB groups, however, only GP did not
      discriminate between new and familiar objects; (2) in the radial-maze task, GP
      and SI/VP lesions produced weak and tran sient impairment whereas MS/VDBB lesions
      produced a large deficit; (3) in the radial-maze task, performance of normal rats
      was improved with physostigmine and impaired with amphetamine. The effect of
      amphetamine was significant on non-memory measures only; (4) neither amphetamine
      nor physostigmine improved memory performances of lesioned rats. These results
      suggest that the septo-hippocampal projections are involved in spatial memory but
      not in object recognition whereas the integrity of Substantia Inno minata/Ventral
      Pallidum does not seem critical for either task. The cholinergic nature of the
      deficit produced by the medial septal lesion remains in question because of
      improvements seen in sham-operated rats but not in lesioned rats.

PMID- 9774489
TI  - Role of endothelial-derived reactive oxygen species and nitric oxide in
      norepinephrine-induced rat aortic ring contractions.
AB  - In the present investigation involvement of endothelial-derived reactive oxygen
      species (ROS) and their interaction with nitric oxide (NO), during norepinephrine
      (NE)-induced contraction of rat aortic rings was studied. NE (1x10(-10) M to
      1x10(-5) M) caused concentration-dependent contractio n of the endothelium intact
      aortic rings. In the presence of hydroxyl radical scavengers, histidine (1x10(-3)
      M), mannitol (3x10(-3) M), dimethyl sulfoxide (50x10(-3) M) or thiourea (1x10(-3)
      m), superoxide dismutase (superoxide radical scavenger, SOD 10 or 100 U ml-1) or
      catalase (hydrogen peroxide inactivator 3, 10, or 100 U ml-1) the concentration
      response curve of NE was shifted towards the right. Interestingly, in NG-nitro-l
      arginine methyl ester (L-NAME) (1x10(-5) M, a NO synthase inhibitor) pretreated
      rings, NE-induced contractions were not inhibited by SOD or extracellular
      hydroxyl radical scavengers (mannitol and histidine). However, in these rings NE
      induced contractions were found to be attenuated by endogenous hydroxyl radical
      scavengers (thiourea and DMSO) or catalase. In the endothelium denuded rings no
      significant effect of these scavengers on NE-induced contractions was observed.
      These results thus indicate the involvement of endothelium-derived hydrogen
      peroxide, superoxide and hydroxyl radicals in the NE-induced contractions. In
      addition, endothelial NO interacts with the ROS generated during rat aortic ring
      contractions.

PMID- 9774490
TI  - Effects of cardio-pulmonary bypass on vancomycin plasma concentration decay.
AB  - The objective of the study was to investigate possible changes in vancomycin
      serum levels induced by cardio-pulmonary bypass (CPB). Ten cardiac patients
      (seven males, three females, aged between 56 and 81), who underwent cardiac
      surgery requiring CPB, took part in the study. Vancomycin (15 mg kg-1) was
      intravenously infused over 60 min before anaesthesia and blood samples were taken
      at appropriate times after drug administration (0, 0.5, 1, 6, 8 h), after
      starting CPB (0, 5, 30 and 60 min) and after aortic unclamping (0, 5, 30, 60, 120
      min). Drug serum concentrations were determined by means of a fluorescence
      polarization immunoassay. The area under the concentration-time curve (AUC)
      measured during CPB were compared with the AUC extrapolated in the same interval
      by fitting a two-compartment pharmacokinetic model to drug concentrations
      obtained before and after CPB. Five minutes after starting CPB vancomycin serum
      levels decreased, on average, by 40.9% and remained steadily lower than the
      expected values over the next 60 min. In the same interval, the measured AUC was
      31.7% lower than the expected AUC. In no instance did serum levels fall below the
      MIC for most common pathogens (1-2 mg l-1). At aortic unclamping serum levels
      slightly rebounded but tended to remain lower than the expected concentrations
      over the next 120 min. In conclusion, during CPB vancomycin serum levels
      invariably decreased but, at the dose employed (15 mg kg-1), remained in a
      potentially effective range for antimicrobial prophylaxis.

PMID- 9774492
TI  - Effects of tamoxifen, melatonin, coenzyme Q10, and L-carnitine supplementation on
      bacterial growth in the presence of mycotoxins.
AB  - The involvement of toxic oxygen intermediates in the bacteriostatic effects of
      mycotoxins (T-2 toxin, deoxynivalenol, ochratoxin A, aflatoxin B1, and fumonisin
      B1) was investigated by producing bacterial growth curves using turbidimetry
      assays in the presence and absence of oxygen radical-scavenging substances. The
      strains used in this study included Escherichia coli (FT 101), Streptococcus
      agalactiae (FT 311, FT 313, FT 315), Staphylococcus aureus (FT 192), Yersinia
      enterocolitica (FT 430), Salmonella infantis (FT 431), Erysipelothrix
      rhusiopathiae (FT 432), Lactobacillus plantarum (FT234) and Lactobacillus casei
      (FT 232). Tamoxifen, melatonin, l-carnitine and coenzyme Q10 were used as radical
      scavengers against oxygen toxicity to the strains studied. Tamoxifen was the most
      effective in inhibiting bacterial growth when used at a high concentration,
      whereas melatonin and l-carnitine were less effective. A combination of l
      carnitine and coenzyme Q10 provided better protection against oxygen toxicity
      caused by the mycotoxins growth than they did individually. It was concluded that
      oxygen radicals are involved in the killing of bacteria and that there is
      endogenous formation of toxic oxygen products by mycotoxins. The objective of
      this study was to determine whether the antioxidants were able to counteract the
      toxic effects of the mycotoxins. The data obtained indicate that bacterial growth
      can be inhibited especially by T-2 toxin, aflatoxin B1 and ochratoxin A and that
      this effect can be partially counteracted by antioxidants such as coenzyme Q10
      plus l-carnitine.

PMID- 9774491
TI  - An in vivo, ex vivo and in vitro comparative study of activity of copper
      oligopeptide complexes vs Cu(II) ions.
AB  - The tetrapeptide-Cu(II) complex H-(l-His-Gly)2-OH/Cu(II), indicated as L-Cu(II),
      has been investigated, as compared to the Cu(II) inorganic salt CuSO4, for its
      antioxidative and anti-inflammatory properties under a panel of experimental
      conditions. Both inorganic and organic Cu(II) compounds showed comparable
      activities in vitro and ex vivo by: (i) protecting, in a dose-dependent manner,
      rat brain homogenates from Fe(III)/ascorbate- or haemoglobin-induced lipid
      peroxidation; (ii) inhibiting the superoxide-mediated ferricytochrome c reduction
      by activated macrophages. CuSO4 and L-Cu(II) also exhibited similar anti
      inflammatory effects in vivo by reducing significantly the extent of carrageenan
      induced edema in the rat paw. The activities of the two compounds diverged
      strikingly only in the xanthine/xanthine oxidase system at low phosphate buffer
      concentration. L-Cu(II) decreased the rate of NBT reduction by superoxide in a
      true SOD-like fashion without affecting urate production. Instead, Cu(II) ions
      caused the rapid xanthine oxidase inactivation thus inhibiting both urate and
      superoxide production; this effect might be ascribed to the superoxide-mediated
      generation of the strong oxidant Cu(III) and its interaction with the enzyme. The
      administration of Cu(II), whether complexed with linear oligopeptides or as an
      inorganic salt, to animals or tissue extracts, conferred protection against
      oxidation and ought, conceivably, to interact with endogenous biological
      molecules and form highly bioavailable complexes which serve, subsequently, as
      the real scavengers. Moreover, the claimed prominent scavenger activities of
      Cu(II)-oligopeptide complexes over inorganic copper ions could be realised only
      in very simple in vitro systems through mechanisms which, although of biochemical
      interest, are unlikely to be of physiopathological significance.

PMID- 9774493
TI  - Lipid peroxidation and antioxidant enzymes in isoproterenol induced oxidative
      stress in rat tissues.
AB  - The oxidative metabolism of catecholamines produce quinones which react with
      oxygen to produce superoxide anions (O2-.) and H2O2. The catecholamines, however,
      are important under stress conditions but may have damaging effects due to the
      generation of reactive oxygen species (ROS) and formation of oxidation products.
      ROS are involved as causative factors in many diseases, therefore, the generation
      of ROS by catecholamines may also contribute to this process. Isoproterenol (ISO)
      was administered to rats in two doses so as to evaluate their beta-adrenergic and
      toxicological actions in terms of lipid peroxidation (LPO) and the changes in the
      antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT),
      glutathione-S-transferase (GST) and glutathione (GSH) content in heart, liver and
      kidney. ISO treatment caused LPO in tissues, however, the heart initially showed
      decreased LPO. This is attributed to the condition of hypertrophy by which the
      heart can protect itself to a limited extent against oxidative stress. The second
      dose of ISO, administered 24 h after the first treatment, showed toxic effects
      resulting in a higher increase in LPO. The increased SOD activity in tissues 3
      days after a dose of ISO suggests that the ROS may induce SOD activity to
      dismutate O2-. However, increased amounts of O2-., inhibited SOD activity at 3
      and 6 h with recovery towards control values at 12 h of a second dose of ISO
      treatment. CAT activity in tissues increased at 6 h of a second dose of ISO
      treatment. The elevated SOD and CAT enzymes in tissues indicate a response due to
      increased ROS. The increase in GSH content in the heart, liver and kidney at day
      2 of ISO treatment and 12 h after the second dose of ISO may also neutralise
      oxidative stress. The inhibition in GST activity in tissues was observed probably
      due to increased ROS generation, however, GST activity partially recovered by 12
      h after the second dose of ISO, in an attempt to counteract oxidative stress. The
      result shows that ISO induced oxidative stress and the increase of the
      antioxidant system in tissues may attenuate oxidative stress. It is suggested
      that ROS generation in the oxidation of catecholamines may be partially
      counteracted by the antioxidant system in tissues.

PMID- 9774494
TI  - Secretory, biosynthetic and cationic responses to 2-(N-PHENYL-INDOYL)IMIDAZOLE in
      rat pancreatic islets.
AB  - The secretory, biosynthetic and cationic effects of a novel insulinotropic agent
      with an imidazoline structure, 2-(N-phenyl-indoyl)imidazole hydrochloride (RX
      871024) was investigated in rat pancreatic islets. In the 1.0-10-microM range,
      this agent augmented, in a concentration-related manner, the release of insulin
      from islets incubated at intermediate concentrations of d-glucose (4.0-7.0 mm),
      this enhancing action fading out at both lower a nd higher d-glucose levels. When
      the concentration of RX 871024 was raised to 1.0 mm, severe inhibition of glucose
      stimulated insulin output was observed. The imidazole derivative (10 microM)
      failed to enhance glucose-stimulated biosynthetic activity in islets exposed to l
      [4-3H]phenylalanine; a modest inhibition of the islet peptide tritiation was even
      recorded at 4.0 mm d-glucose. The positive insulinotropic action of RX 871024 (10
      microM) coincided with a decrease in 45Ca net uptake, unchanged outflow of 86Rb
      and stimulation of 45Ca efflux from prelabelled islets, the latter effect being
      only partially suppressed in the absence of extracellular Ca2+. These findings
      suggest a multifactorial mode of action of RX 871024 in islet cells, with
      emphasis on both an apparent stimulation of Ca2+ influx and, independently of
      this effect, an intracellular redistribution of the divalent cation. The
      imidazole compound is proposed, therefore, to display suitable attributes to
      bypass site-specific defects of d-glucose metabolism in the B-cell of non-insulin
      dependent diabetic patients.

PMID- 9774495
TI  - Radioiodine treatment and oxidative stress in thyroidectomised patients for
      differentiated thyroid cancers.
AB  - Post-operative radioiodine treatment of differentiated thyroid cancer occupies a
      well determined place in the treatment policy of this disease. Since little is
      known about erythrocytes oxidant and antioxidant status in patients with thyroid
      cancers after radioiodine treatment, we measured erythrocyte malondialdehyde
      (MDA) levels, as a marker of lipid peroxidation, erythrocyte reduced glutathione
      (GSH) levels and activities of GSH-Peroxidase and GSH-Reductase as antioxidants.
      We found that erythrocyte MDA levels were significantly higher, and erythrocyte
      GSH levels and activities of GSH-related enzymes were significantly lower in
      thyroidectomised patients after surgery than in healthy controls. Additionally,
      according to their thyroid hormone levels the patients had hypothyroidism at this
      time. In patients 2 days after radioiodine treatment both MDA and GSH levels and
      GSH-related enzyme activities were significantly increased when compared to their
      own initial levels. In conclusion, we suggested that radioiodine could facilitate
      or induce significant oxidant/antioxidant changes in erythrocytes-indirectly as a
      result of the internal radiotherapy with radioiodine.

PMID- 9774496
TI  - L-type calcium channels modulate the regression of left ventricular hypertrophy
      after ace-inhibition in genetic hypertension.
AB  - The aim of this study was to investigate the possible link between the regression
      of the left ventricular mass induced by ACE-inhibition and L-type calcium
      channels. For this purpose, an evaluation of both L-type calcium channels and AT1
      receptor patterns in the left ventricular tissue of adult spontaneously
      hypertensive rats (SHR) was made before and after long-term treatment with
      ramipril. An abnormal density of both dihydropyridine and AT1 receptors was
      observed in SHR at 24 weeks, compared to age-matched control Wistar-Kyoto (WKY)
      rats (dihydropyridine receptor Bmax: 1. 30+/-0.09 vs 1.14+/-0.06 pmol mg-1
      proteins, P<0.001; AT1 receptor Bmax: 1.35+/-0.07 vs 2.62+/-0.08, P<0.001 pmol mg
      1 proteins). A treatment for 10 weeks with ramipril induced a significant
      decrease in the left ventricular mass index of SHR, as well as a significant
      decrease in dihydropyridine receptor density (Bmax: 0.96+/-0.01 vs 1. 39+/-0.08
      pmol mg-1 proteins, P<0.001) and a significant increase in AT1 receptor density
      (Bmax: 3.08+/-0.26 vs 2.78+/-0.09 pmol mg-1 proteins, ramipril-treated SHR vs
      vehicle-treated SHR, P<0.001). These results suggest that the decrease in left
      ventricular mass after treatment with ramipril may be dependent on changes in L
      type calcium channels other than the direct effect on circulating and tissue
      angiotensin II (ang II) levels: involvement of calcium channels and subsequent
      calcium influx into cardiac cells could be proposed as an additional mechanism
      for the regression of left ventricular mass after ACE-inhibition.

PMID- 9774497
TI  - Enamel structure and development and its application in hominid evolution and
      taxonomy.

PMID- 9774498
TI  - Growth tracks in dental enamel.
AB  - The present paper evaluates the enamel growth tracks as tools in the
      chronological mapping of dental development, with special reference to hominids.
      Dental enamel consists of tightly packed hydroxyapatite crystals organized by
      differential orientation into a pattern of prisms and interprisms. The crystal
      organization is probably under the influence of both cellular and physico
      chemical factors. The structure of mature enamel testifies to events that took
      place during enamel formation. The prisms are the fossilized tracks traced out by
      ameloblasts. The tangential diameter of ameloblasts and the central distance of
      prisms increase from the enamel-dentine junction to the enamel surface. Available
      evidence suggests that prism cross-striations are light microscopic expressions
      of prism varicosities and/or compositional variations, that these are due to a
      rhythm in enamel formation, and that this rhythm is diurnal. In human enamel the
      mean daily rate of enamel production is about 3.5 micron, but increases from
      inner to outer enamel and decreases from incisal/cuspal to cervical enamel.
      Conclusive evidence has shown that Retzius lines are incremental lines. Evenly
      spaced Retzius lines probably represent a 6-11 day rhythm in enamel formation,
      while other Retzius lines may be due to various types of stress. The geometry of
      the enamel growth tracks and their chronological significance are valuable tools
      in chronological mapping of dental development and for understanding temporal and
      spatial patterns in tooth morphogenesis. The taxonomic significance of prism
      packing patterns, prism decussation and enamel thickness should be clarified
      through further systematic descriptive research.

PMID- 9774499
TI  - Radiographic and histological methodologies in estimating the chronology of crown
      development in modern humans and great apes: a review, with some applications for
      studies on juvenile hominids.
AB  - There has been a burgeoning of interest in the last decade on growth studies in
      hominids. These studies have relied heavily on dental development, and have
      compared juvenile hominids to modern human and ape standards, which are usually
      established using radiographic data. There has been considerable discussion on
      the most appropriate methods of deriving population standards from radiographs,
      but very little on the accuracy of the radiographic image itself. Previous
      histological and dissection studies have shown that age at onset of
      mineralization is overestimated, and age at crown completion is underestimated
      using radiographs. This study considers the process of X-ray absorbence by
      mineralized tissues and the formation of radiographic images of developing teeth.
      Following tooth initiation a critical mass of mineral is required for the tooth
      to register superimposed on the absorbence of alveolar crypt bone, which accounts
      for the late identification of tooth initiation. Determination of completion of
      crown growth depends upon the identification of the last formed enamel at the
      cervix. Recognition of this key stage is difficult as crown growth slows towards
      the cervix, and the last secreted enamel may take months to attain full
      mineralization levels due to the prolonged maturation process. Morphological and
      geometric factors have a significant influence on the imaging of the completed
      crown. The last formed enamel is located on the buccal face, where enamel thins
      progressively to nothing. X-ray absorption by enamel at the cervix becomes
      insignificant, and may be counterbalanced by increased dentine absorption.
      Approximal enamel in contrast is clearly visualized once maturation is complete.
      However, developmentally this enamel face initiates later, and is completed much
      earlier than buccal enamel. All of the radiographic estimates of crown completion
      times are based upon interpretations of approximal enamel completion. These
      considerations suggest that the human population standards in current usage may
      not represent true anatomical and chronological stages of crown development, and
      care should be taken in referring juvenile hominids to these radiological
      standards.

PMID- 9774500
TI  - Do enamel microstructures have regular time dependency? Conclusions from the
      literature and a large-scale study.
AB  - This paper is structured in two parts. The first briefly reviews a number of
      lines of published evidence, including direct experimental evidence, supporting
      the contention that enamel microstructures are time dependent and have a regular
      periodicity. The second presents the results of a large-scale study designed to
      test a central assumption underlying most histological ageing approaches in
      enamel: that the number of cross striations between adjacent striae of Retzius,
      called the circaseptan interval, are uniform within a tooth and between all teeth
      in the dentition of an individual. The study uses a sample of 158 anterior teeth
      from three modern human populations. Teeth were sectioned and circaseptan
      intervals were determined by dividing measurements of the distance between
      adjacent striae of Retzius, by cross-striation length. In order to exercise as
      much procedural rigour as possible, all measurements were made from
      photomicrographs. Two sections were taken from each tooth, the sampling location
      within each tooth was recorded, and all populations included multiple teeth from
      single individuals. Results statistically validate the uniformity hypothesis
      within the anterior dentition. These, together with the weight of published
      evidence, suggest that data derived from the use of enamel microstructures in age
      estimation techniques and growth and development studies, are valid.

PMID- 9774501
TI  - Utilization of periodic markings in enamel to obtain information on tooth growth.
AB  - Enamel retains two fundamental periodic markings: the prism cross-striations,
      marking a diurnal rhythm of prism elongation, and the striae of Retzius, a longer
      term marker of formation of the enamel surface. It is argued that, while
      artefacts superficially resembling prism cross-striations can be observed, these
      should not mislead an experienced histologist and that true cross-striations are
      reliable markers of the daily incremental apposition of enamel. The incremental
      markings can be used to elucidate several aspects of tooth crown growth. (1) Rate
      of enamel apposition. In some teeth, e. g., hominoid permanent teeth, the enamel
      apposition rate increases progressively between the inner and outer enamel, while
      in others the apposition rate appears to be uniform. (2) Crown formation time.
      This can be estimated on intact teeth, using counts of perikymata (surface traces
      of the striae), together with information on the time interval between successive
      striae. Much better estimates can be obtained from sections, using counts of
      cross-striations. (3) Pattern of crown formation. The rate at which new enamel
      formation extends over the presumptive enamel-dentine junction (extension rate)
      can be estimated from knowledge of the cross-striation interval together with
      angular measurements of prisms and striae. Multiple measurements of the extension
      rate within a tooth can be used to provide an estimate of crown formation time.
      The main application of extension rate measurements is to give quantitative
      information on the pattern of crown formation. In large primate teeth, the
      extension rate is high early in crown formation and slower later in crown
      formation. In smaller, more rapidly-formed teeth, a gradient in extension rate
      appears to be absent. Enamel thickness is negatively correlated with extension
      rate among primates. This seems to be a mechanism ensuring that there is
      sufficient time for enamel maturation to be completed before eruption takes
      place. Among primates it appears that variation in the prism pattern (i.e., the
      extent to which the outline of the pattern 3 prisms is closed or open) is
      correlated with the extension rate. It is postulated that the extension rate
      controls prism shape by influencing the morphology of the Tomes process pits
      during their initial formation.

PMID- 9774502
TI  - Observations on stria morphology in the lateral enamel of Pongo, Hylobates and
      Proconsul teeth.
AB  - The enamel of certain primates (orang-utans, siamangs and the early Miocene
      fossil hominoid, Proconsul) occasionally contains striae of Retzius that appear
      distinct from those more typical of the lateral and cervical enamel of other
      anthropoids. These striae can be described as "S-shaped" since their contour is
      markedly sinuous as it passes from the enamel dentine junction (EDJ) to the tooth
      surface. "S-shaped" striae have never been described in the comparative
      literature on primate enamel and yet they may be of some phylogenetic
      significance. This study explores the interrelationship between four variables in
      the enamel of an orang-utan, a siamang and a specimen of Proconsul heseloni (from
      Rusinga Island, Kenya) all of which contain "S-shaped" striae. The morphological
      components of this form of stria have been quantified here. The four variables
      measured were (1) prism width; (2) the angle the prisms make to the EDJ; (3) the
      angle the striae of Retzius make with respect to the EDJ, and (4) the daily rate
      of enamel formation. Each of these four variables was measured in inner enamel
      close to the EDJ, in enamel mid-way between the EDJ and the enamel surface, and
      in outer enamel. Our aim was both to quantify the components of "S-shaped" striae
      and to attempt to offer a developmental explanation for the appearance of these
      striae in fully formed enamel. We conclude that "S-shaped" striae may be
      associated with regions of lateral enamel where prism width either remains
      constant or even reduces as the enamel surface is approached. This, together with
      an increase in the linear daily rate of enamel secretion towards the outer
      enamel, a cervical inclination in the angulation of the prisms with respect to
      the EDJ, and an increased angulation of the striae of Retzius to the EDJ are all
      features that characterize "S-shaped" striae. This description will facilitate
      identification and quantification of any similar striae in the enamel of other
      primates. It will also allow careful comparison of each of the four variables one
      with another which may in turn help in establishing "S-shaped" striae as
      developmentally homologous between species.

PMID- 9774503
TI  - Histological reconstruction of dental development and age at death in a juvenile
      gibbon (Hylobates lar).
AB  - Although research on dental development in great apes and modern humans has
      provided comparative models for life history, growth and development in hominin
      evolution, almost nothing is known about dental development in their sister
      group, the hylobatids. Hylobatids are of interest because they differ in
      important life history variables from other catarrhines of similar body mass, and
      can help to provide more general models for the factors underlying patterns of
      dental development. This study uses histological techniques to reconstruct
      developmental sequence, crown formation times, root extension rates, daily rates
      of enamel and dentine formation, and age at death in a single specimen of
      Hylobates lar. Thin sections were prepared of permanent mandibular teeth and
      analyzed by polarized light microscopy. Age at death was determined to be 2.88
      yrs calibrated from a pattern of accentuated growth increments. At this age,
      permanent teeth in occlusion include I1, I2, and M1. Developing permanent teeth
      include C1, P3, P4, and M2. P3 lags behind P4 in development, and there is no
      indication of M3 present in the crypt. Differences between the gibbon specimen
      and great apes include greater prenatal development of M1, accelerated incisor
      development relative to molars and prenatal development of I1, no overlap between
      M2 and M3 crown development, shorter crown formation times, and slower root
      extension rates of 4-5 micron daily in the molars. Root extension rates are
      higher in the incisors. The periodicity of growth increments is four days, more
      similar to macaques than to other hominoids. Daily formation rates for enamel of
      1.2-4.9 micron and dentine of 1.7-4.9 micron are similar to those reported for
      other catarrhines.

PMID- 9774504
TI  - A histological reconstruction of dental development in the common chimpanzee, Pan
      troglodytes.
AB  - Much is known about the dental development of Pan compared with that for other
      extant great apes. The majority of information available has concentrated either
      on the emergence times of teeth or on the sequence of mineralization stages of
      the teeth as revealed from radiographs. However, the problems of defining stages
      of tooth formation sufficiently accurately on radiographs are only now becoming
      recognized. All of the data available to date suggest the presence of a more
      variable picture for the timing of mineralization stages in chimpanzees than for
      the timing of tooth emergence. In particular, arguments persist in the literature
      over the time of initial mineralization and the time it takes to form each
      anterior tooth crown in chimpanzees. Therefore we attempt to provide a more
      precise chronological time scale for dental development in our closest living
      relative. Furthermore, we examine the sequence of molar cusp formation relative
      to enamel formation times related specifically to those cusps and to try to tie
      these data in with information from functional studies of molar crowns.
      Histological sections of 14 maxillary and 28 mandibular teeth from four
      chimpanzee (Pan troglodytes) individuals and three molar teeth from three
      chimpanzees of unknown origin were prepared in accordance with a well-established
      protocol. By combining data on short-period and long-period incremental lines
      (including daily secretion rates, periodicity, prism lengths and enamel
      thickness) in both enamel and dentine, we reconstruct times for the onset and
      duration of crown formation as well as construct a schedule for the pattern and
      timing of dental development in this one hominoid species. Interestingly, our
      histologically-derived data confirms that the data from radiographic studies
      underestimate crown formation times by the following amounts for each tooth type:
      I1 2.5 years, I2 3.1 years, C 1.6 years, P3 1.9 years, P4 0.1 years, M1 0.8
      years, M2 1.1 years and M3 0.3 years. When combined with data on gingival
      emergence, it seems that chimpanzee teeth have a greatly reduced time for root
      growth before emergence occurs and that the major differences between Homo
      sapiens and Pan lie in the first part of the root formation rather than in the
      total period of crown formation. Maxillary and mandibular molar functional cusps
      take longer to complete enamel formation to the cervix than any other cusp in
      that same tooth, which makes sense as these cusps are thick enamelled. These
      results suggest that new links can be made between developmental aspects,
      occlusal morphology and tooth function.

PMID- 9774505
TI  - A comparative study of cross striation spacings in cuspal enamel and of four
      methods of estimating the time taken to grow molar cuspal enamel in Pan, Pongo
      and Homo.
AB  - Cusps of three second permanent molar teeth belonging to Pan, Pongo and Homo
      respectively, were chosen where enamel cross striations were easily observed and
      measured using polarizing light microscopy. Prisms were tracked outwards on
      photomontages from the dentine horn to the surface of the tooth just lateral to
      the central gnarled enamel over the cusp tip. Approximately monthly zones of
      enamel formation were identified and mean cross striation spacings calculated for
      each zone within each of the three cusps and for the whole of each cusp in total.
      Enamel secretion rates ranged from 2.5 to 6.5 microns per day with an overall
      mean value in Pan and Homo of 4 microns per day and of 4.4 microns per day in
      Pongo for the cuspal enamel. Two of these cusps (of Pan and Pongo) and another of
      a third permanent molar of Homo were selected for further analysis. Four methods
      were employed to estimate cuspal enamel formation time. (i) Total counts of
      enamel cross striations were made through the lateral cuspal enamel on
      photomontages. The points in the dentine and at the enamel dentine junction (EDJ)
      corresponding to the end of cuspal enamel formation were defined using
      incremental and accentuated markings. (ii) Measurements of the average daily
      rates of dentine formation in each cusp were divided by the length of the axial
      cuspal dentine formed to give the time of cuspal dentine formation. (iii) A
      cumulative prism length was calculated close to the EDJ to the end of cuspal
      enamel formation and divided by the mean cross striation repeat interval along
      the EDJ to give an estimate of cuspal enamel formation time. (iv) A cumulative
      time for cuspal enamel formation along the EDJ was calculated by summing
      successive extension rates for known lengths of the EDJ. This was computed using
      the formula derived by Shellis (Archs. oral Biol. 29: 697-705, 1984) based on the
      average daily rate of enamel secretion, the angle of the prisms to the EDJ and
      the angle of the incremental lines to the EDJ. Each of these methods gave results
      to within 5% or 10% of a average value for cuspal enamel formation time derived
      for each cusp. There was no clear indication of additional enamel decussation in
      any of the cusps studied beyond that recorded in the total counts of cross
      striations as the prisms were tracked in two dimensions through the lateral
      cuspal enamel. The results of this study suggest that any one of the methods
      outlined here may give equivalent estimates of cuspal enamel formation if
      suitable incremental markings exist in the region being studied.

PMID- 9774507
TI  - A radiographic study of the development of the human mandibular dentition.
AB  - This paper presents new data on the absolute timing of the growth of the
      mandibular permanent teeth, with an emphasis on the timing of the completion of
      the enamel crown. Two collections of cranio-dental radiographs were analyzed: (1)
      267 juveniles from a contemporary pediatric dental clinic (Case Western Reserve
      University School of Dentistry, Cleveland, Ohio), and (2) 36 individuals sampled
      longitudinally from the Bolton-Brush Growth Study Center. The ages of the
      individuals span from three months to 18 years of age and the study includes both
      cross-sectional and longitudinal data. Comparisons of the ages of attainment of
      the Cleveland samples with other schedules of dental development are made. The
      relative contribution of the multiple underlying sources of variation producing
      the differences between the radiographically based developmental schedules remain
      elusive.

PMID- 9774506
TI  - Histological reconstruction of dental development in four individuals from a
      medieval site in Picardie, France.
AB  - The majority of dental development studies in modern humans are based on
      radiographic analysis. In comparison, very few full histological studies have
      been carried out. In the present study, the onset of enamel formation and crown
      formation time have been established by histological analysis of the complete
      dentition in a medieval French individual. Crown formation times were established
      for the dentition of three further individuals. The number of cross-striations
      between adjacent striae of Retzius was measured and accentuated striae were used
      to construct a chart of the chronology of tooth development. Results on crown
      formation times in individual teeth when compared with previous histologic
      studies are slightly greater than values in a modern African male and near to or
      less than values in (M1) and (I) respectively in a modern population from
      Spitalfields, London. Histologically derived crown initiation times are earlier
      than those reported for radiographic studies. Values for crown formation times
      derived in general from radiographic studies are less than those of our study.
      Attention has recently been focused on the overlap of molar development as a key
      character for distinguishing between humans and great apes. In this study, there
      is an overlap in crown formation between M1 and M2 of 0.27 years and a temporal
      delay of 1.7 years between M2 crown completion and the initiation of the M3.

PMID- 9774508
TI  - Variations in molar enamel thickness among primates.
AB  - Because of its hardness, resistance to abrasion and its influence on crown
      morphology, molar enamel thickness is an important factor in adaptation of the
      dentition to the diet. Enamel thickness has also been discussed extensively in
      relation to the phylogenetic relationships among the hominoids. The aims of this
      study were: (1) to analyse enamel thickness/tooth size relationships among
      primates as a whole, and (2) to evaluate variations in enamel thickness among
      hominoids against the background of the other primates. We employed measures of
      tooth size, and of enamel thickness and quantity based on measurements of areas
      in longitudinal sections of 125 molars of 39 species. Among primates, there were
      two grades of enamel thickness, prosimians having thinner enamel for a given
      tooth size or body weight than anthropoids. The scaling of enamel thickness with
      tooth size and body weight tended to show positive allometry among anthropoids.
      Comparison of hominoid enamel thicknesses with that in anthropoids led to the
      conclusion that Hylobates has enamel of average thickness, Homo has thick enamel
      and Gorilla has thin enamel, while Pan and Pongo had average or thin enamel,
      depending on tooth type. These results may be relevant to considerations of
      hominoid evolution.

PMID- 9774509
TI  - Enamel thickness and the topography of the enamel-dentine junction in South
      African Plio-Pleistocene hominids with special reference to the Carabelli trait.
AB  - This study explores the internal morphology of early hominid teeth using high
      resolution computed tomography. Data on Carabelli feature size, enamel thickness,
      and the topography of the enamel-dentine junction are considered together in
      order to examine the relationship among these variables in the maxillary molars
      of gracile and robust australopithecines from South Africa. In particular, one
      aim is to investigate the degree to which Carabelli feature size influences
      enamel thickness in the plane of the mesial cusps. The results demonstrate that
      maxillary molars attributed to Australopithecus africanus from Sterkfontein,
      Taung and Makapansgat possess larger Carabelli features and thinner enamel along
      the lingual wall of the protocone than do specimens attributed to Paranthropus
      robustus from Swartkrans and Kromdraai. Distinct differences in the position of
      the Carabelli feature at the level of both the enamel-dentine junction and tooth
      crown surface between early hominid species may help explain the observed
      disparity in enamel thickness at that region of the tooth crown as well as offer
      clues to the functional role of Carabelli's cusp. As the size and position of the
      Carabelli feature affects the linear thickness of enamel at this one particular
      region of the tooth crown, future comparative studies focusing on taxa that
      possess moderate to strong development of the Carabelli complex should use the
      linear thickness of enamel taken close to the protoconal dentine horn or at the
      maximum projection of the Carabelli's cusp.

PMID- 9774511
TI  - Editorial 

PMID- 9774510
TI  - Can enamel microstructure be used to establish the presence of different species
      of Plio-Pleistocene hominids from Omo, Ethiopia?
AB  - Microstructural characteristics of enamel are minimally influenced by extrinsic /
      non-genomic factors and are thus potentially important in any attempt to
      establish the taxonomic attribution of Plio-Pleistocene hominids. The aim of this
      work is to assess the potential use of enamel microstructural characteristics in
      attributing teeth from the Omo to different Plio-Pleistocene hominid species.
      First, the results from this study are compared to data for extant hominoids in
      order to observe whether Omo teeth show similar or larger variation. This might
      suggest that more than one species is represented in the Omo sample.
      Alternatively, a similar or smaller variation would suggest that no more than one
      species could be reliably recognized in the sample using enamel microstructural
      characteristics. Secondly, since all previous studies suggest that more than one
      species is present in the large sample of teeth from the Omo, enamel
      microstructure characteristics with the largest variability are used to group
      teeth into morphs. These morphs are compared with previous taxonomic attributions
      of Omo teeth in order to determine if the morphs grouped teeth in a similar way
      to previous studies. The results of this study demonstrate that enamel
      microanatomy characteristics in Plio-Pleistocene hominid teeth from the Omo do
      not present a larger variation than that observed in extant hominoid species.
      This suggests that no more than one species can be recognized by using these
      characteristics. These results also indicate a large overlap in enamel
      microstructure characteristics between Plio-Pleistocene hominid species from Omo
      and place serious doubt on the theoretical potential for using enamel
      microstructural characteristics as a taxonomic tool. The morphs defined in this
      study do not correspond with any previous taxonomic attributions based on
      macrostructural analysis of the same teeth and cannot be referred to different
      species. However, macrostructural characteristics have never been assessed in the
      same way in extant hominoids and it remains to be seen to what extent these
      characters reflect interspecific, intraspecific or even intra-individual
      variation. For now therefore, the taxonomy of Plio-Pleistocene hominids from the
      Omo still remains unresolved.

PMID- 9774513
TI  - Color plates for article numbers ME980642, ME980646, ME980649, and ME980650 

PMID- 9774512
TI  - Analysis of protein and DNA-mediated contributions to cooperative assembly of
      protein-DNA complexes.
AB  - The cooperative assembly of protein-DNA complexes is a widespread phenomenon that
      is of particular significance to transcriptional regulation. Assembly of these
      complexes is controlled by the chemistry of the macromolecular interactions. In
      this sense, transcriptional regulation is a chemical issue. The purpose of this
      review is to present an analytical approach designed to understand this
      regulation from a chemical perspective. By investigating the solution
      interactions between all combinations of molecules, protein-protein, protein
      ligand, and protein-DNA, and the interplay between them, it is possible to
      determine the relative free energies of the different configurations of the
      regulatory complex. This governs their distribution and thereby controls the
      biological activity. To illustrate the approach, we will address the molecular
      basis for cooperativity in the bacteriophage lambda, lysogenic-lytic switch
      mechanism, a system that has long served as a paradigm for gene regulation. The
      driving force for cooperativity in the assembly of gene regulatory complexes is
      generally thought to be provided by direct protein-protein interactions. However,
      other interactions mediated by both proteins and DNA are also involved and may be
      critical to the regulatory mechanism. We will review advances over the past
      several years in the application of biophysical chemical methods to investigate
      protein-protein and protein-DNA interactions. Many of these applications were
      first employed for the lambda system. In addition to describing the physical
      basis for the methods, we will focus on the unique information that can be gained
      and how to combine the information obtained from several techniques to develop a
      comprehensive view of the critical regulatory interactions.

PMID- 9774514
TI  - In situ hybridization with 33P-labeled RNA probes for determination of cellular
      expression patterns of liver transcription factors in mouse embryos.
AB  - Murine hepatocyte nuclear factor-3beta (HNF-3beta) protein is a member of a large
      family of developmentally regulated transcription factors that share homology in
      the winged helix/fork head DNA binding domain and that participate in embryonic
      pattern formation. HNF-3beta also mediates cell-specific transcription of genes
      important for the function of hepatocytes, intestinal and bronchiolar epithelium,
      and pancreatic acinar cells. We have previously identified a hepatocyte and
      pancreatic cut-homeodomain transcription factor, HNF-6, which is required for HNF
      3beta promoter activity. In this study, we used in situ hybridization studies of
      stage-specific embryos to demonstrate that HNF-6 and its target gene, HNF-3beta,
      are coexpressed in the foregut endoderm and in the pancreatic and hepatic
      diverticulum. More detailed analysis of HNF-6 and HNF-3beta's developmental
      expression patterns provides evidence of colocalization in hepatocytes,
      intestinal epithelium, and pancreatic ductal epithelium and exocrine acinar
      cells. In support of the role of HNF-6 in regulating HNF-3beta expression in
      developing hepatocytes, their liver expression levels are both transiently
      reduced between 14 and 15 days of gestation. At day 18 of gestation and in adult
      pancreas, HNF-6 and HNF-3beta transcripts remain colocalized in the exocrine
      acinar cells, but their expression patterns diverge in endocrine cells. HNF-3beta
      expression is restricted to the endocrine cells of the islets of Langerhans,
      whereas the ductal epithelium expresses HNF-6. We discuss these expression
      patterns with respect to specification of hepatocytes and differentiation of the
      endocrine and exocrine pancreas.

PMID- 9774515
TI  - Molecular aspects in feedback regulation of gene expression by cholesterol in
      mammalian cells.
AB  - Intracellular cholesterol balance is maintained by a tight feedback mechanism
      that prevents the overaccumulation of cholesterol to cytotoxic levels. This is
      achieved through the coordinate regulation of genes of cholesterol uptake and
      biosynthesis by the sterol regulatory element binding proteins (SREBPs). The
      SREBPs are synthesized as membrane bound precursors that are released from their
      membrane tether when the cell needs new cholesterol. In the present article we
      present a model for how the cholesterol uptake pathway may be activated before
      the biosynthetic pathway to prevent wasting cellular energy and carbon on
      unneeded synthesis. Then we introduce a system for analyzing the differential
      localization and cellular trafficking of the different SREBP isoforms that can be
      performed over time in living cells.

PMID- 9774516
TI  - Use of human placental alkaline phosphatase transgenes to detect somatic mutation
      in mice in situ.
AB  - Methods for in situ detection of cells that have suffered a specific mutation
      would be valuable for understanding somatic genetic mosaicism, a phenomenon that
      underlies a variety of diseases including cancer. Such methods would also be
      valuable in studying changes in gene expression, whether programmed by the cells
      or caused by exogenous forces, such as exposure to genotoxins or infection by a
      virus. To improve methods for detection of genetic change at the cellular level
      in animal tissues, we used the human placental alkaline phosphatase (PLAP) gene.
      The PLAP gene sequence was modified such that it could no longer produce
      functional PLAP enzyme. Mutant PLAP genes were placed in the mouse genome, and
      populations of cells carrying these mutant PLAP genes were studied to determine
      the fraction of cells that would acquire PLAP activity. Spontaneous and induced
      reversion of mutant PLAP genes was studied in cultured cells and in the tissues
      of transgenic mice. The data obtained from these studies show the utility of in
      situ reporter genes such as PLAP for detection of variant cells within a tissue.

PMID- 9774517
TI  - Approaches to study interactions between small DNA viruses and differentiated
      tissue.
AB  - Polyomavirus (Py) derives its name from the early observation of multiple tumors
      that develop in newborn mice following inoculation with this family of viruses.
      In nature, however, tumor development is rare in the virus life cycle, rather a
      two-phase infection occurs, acute and persistent, resulting in a final latent
      infection in the kidneys. The acute phase induces an antiviral immune response,
      although no recognizable inflammation, which can last the lifetime of the mouse,
      even passing on antibodies to its offspring. The structure, replication, and
      expression of the Py viral genome in permissive and nonpermissive infections has
      been studied extensively in various cell culture systems. However, the nature of
      Py expression, replication, and immunopathogenesis in mice has not been
      thoroughly researched.

PMID- 9774518
TI  - Regulation of gene expression by HTLV-I Tax protein.
AB  - The human T-cell leukemia virus type I or HTLV-I is the causative agent of adult
      T-cell leukemia. A protein encoded by HTLV-I, Tax, activates viral gene
      expression and is essential for transforming T-lymphocytes. Tax activates HTLV-I
      gene expression via interactions with the ATF/CREB proteins and the coactivators
      CBP/p300 which assemble as a multiprotein complex on regulatory elements known as
      21-bp repeats in the HTLV-I LTR. Tax can also activate expression from cellular
      genes including the interleukin-2 (IL-2) and the IL-2 receptor genes via
      increases in nuclear levels of NF-kappaB. Tax modulation of gene expression via
      the ATF/CREB and NF-kappaB pathways is linked to its transforming properties.
      This review discusses the mechanisms by which Tax regulates viral and cellular
      gene expression.

PMID- 9774519
TI  - Interactions between a herpes simplex virus regulatory protein and cellular mRNA
      processing pathways.
AB  - The herpes simplex virus type 1 (HSV-1) immediate-early regulatory protein ICP27
      performs essential functions during viral lytic infection. Studies with viral
      mutants have demonstrated that ICP27 affects the shutoff of host protein
      synthesis, HSV-1 DNA replication, and the expression of viral early and late
      genes. Mounting evidence has been presented to demonstrate that ICP27 functions
      predominantly at the posttranscriptional level by affecting mRNA processing. That
      is, ICP27 alters poly(A) site usage, impairs host cell splicing, and facilitates
      the export of viral intronless mRNAs. These diverse effects occur by the
      interaction of ICP27 with viral and host proteins and by binding RNA. To define
      the precise mechanisms by which ICP27 affects RNA processing pathways, it is
      necessary to identify all of the molecular interactions of ICP27 in vivo and to
      determine the functional significance of these interactions. In vivo approaches
      will be emphasized here. Protein-protein interactions have been analyzed by
      coimmunoprecipitation studies, followed by immunoblotting to confirm the identity
      of coprecipitating proteins. Indirect immunofluorescence staining has been
      performed on cells treated with RNA polymerase II inhibitors to determine the
      intracellular distribution of ICP27 related to its RNA export function. Finally,
      in vivo UV irradiation has been used to covalently cross-link ICP27 to mRNAs in
      direct contact. This was followed with procedures to isolate and analyze the
      protein-RNA complexes. These studies have revealed several splicing complex
      proteins with which ICP27 interacts and have identified a number of intronless
      RNA transcripts to which ICP27 binds in the nucleus and cytoplasm in its role in
      RNA transport.

PMID- 9774520
TI  - Analysis of factors influencing kinetics of herpes simplex virus transcription
      utilizing recombinant virus.
AB  - The herpes simplex virus type 1 (HSV-1) transcription program is a regulated
      cascade in which early and late phases of gene expression are separated by viral
      DNA replication. While promoters controlling expression of transcripts encoding
      immediate-early proteins contain virus-specific cis-acting elements, these are in
      the context of cellular promoter elements, and the promoters controlling
      expression of other viral transcripts contain only cellular cis-acting elements.
      We had developed and continue to refine a general method for the production of
      recombinant viruses in which modified promoters can be inserted into nonessential
      loci within the viral genome through homologous recombination. This approach has
      been especially useful in defining the features of model promoters of the various
      kinetic classes. Our work suggests that class-specific differences in promoter
      architecture are critical factors in the ability of the cellular transcription
      machinery to form stable preinitiation complexes at various phases of infection
      and, thus, mediate kinetic class-specific transcription. Early (beta) promoters
      contain a TATA box and upstream activation elements while sequences downstream of
      the TATA homology are dispensible for transcription. Late transcripts can be
      catagorized as either leaky-late (beta gamma) or strict late (gamma) depending on
      whether they are readily detectable prior to viral DNA replication. Promoters
      controlling both types are clearly distinct from early ones in that sequences
      near the transcription start site which resemble consensus mammalian initiator
      elements are required along with the TATA box and activator elements. Strict late
      promoters do not contain elements upstream of the TATA box but include what
      appears to be a class specific element downstream of the transcription start
      site.

PMID- 9774521
TI  - Generation and use of recombinant reporter viruses for study of herpes simplex
      virus infections in vivo.
AB  - It has become increasingly clear that the fate of herpes simplex virus (HSV)
      infections involves complex interactions between the virus and the specific cell
      types that comprise the tissues of the animal host. No reliable cell culture
      system for studying the establishment of latency and reactivation exists, and
      therefore these studies must be performed within animal models. One difficulty in
      elucidating the molecular regulation of these events is in determining the
      transcriptional activity of key viral genes during different stages of the
      infection in vivo. The heterogeneous cell types comprising infected tissues make
      PCR analysis of tissue homogenates difficult to interpret. The need to
      characterize expression of multiple transcriptional markers reliably and
      quantitatively at the level of individual cells is therefore key to determining
      the interplay between viral and cellular genes during latency and reactivation.
      Here we discuss the construction and evaluation of HSV reporter viruses that have
      been used in these analyses. HSV-1 recombinants have been engineered with
      representative viral promoters driving beta-galactosidase as a reporter.
      Methodology used to evaluate the levels of gene expression using (1) quantitative
      enzyme assays, (2) precipitatable substrate assays to localize the positive
      cells, and (3) immunohistochemistry and fluorescence assays to look at
      colocalization of markers during in vivo infection is presented. In addition to
      studying the molecular pathogenesis of HSV, the application of similar reporter
      viruses to evaluate promoters for targeting various differentiated tissues will
      be useful in developing these viruses as potential vectors for gene therapy.

PMID- 9774522
TI  - Growth of human cytomegalovirus in primary macrophages.
AB  - Human cytomegalovirus (HCMV) is a major human pathogen that causes considerable
      disease among immunocompromised individuals. A primary infection results in life
      long persistence of the virus in a latent form. HCMV is known to be transferred
      by blood products, bone marrow, and solid organs, but the cell type that carries
      the latent infection has been difficult to identify. We have recently
      demonstrated reactivation of latent HCMV in allogeneically stimulated monocyte
      derived macrophages (Allo-MDM). Reactivation occurred only in macrophages
      produced by allogeneic but not mitogenic stimulation. The presence of dendritic
      cell markers on some Allo-MDM cells suggested that these macrophages were related
      to dendritic cells. However, dendritic cells obtained by stimulation of monocytes
      with interleukin-4 (IL-4) and granulocyte-macrophage colony stimulating factor
      (GM-CSF) were not permissive for HCMV infection. The cellular and cytokine
      components which are essential for HCMV replication and reactivation of virus
      were also examined in Allo-MDM. The importance of both CD4- or CD8-positive T
      cells in the generation of HCMV permissive Allo-MDM was demonstrated by negative
      selection or blocking experiments using antibodies directed against both HLA
      class I and HLA class II molecules. Examination of the cytokines essential for
      the generation of HCMV permissive Allo-MDM identified gamma-interferon (IFN
      gamma, but not IL-1, IL-2, tumor necrosis factor alpha, or GM-CSF as critical
      components in the generation of these macrophages. However, addition of IFN-gamma
      to unstimulated macrophage cultures was insufficient to reactivate virus. These
      results indicate the importance of a specific moncyte stimulus in the generation
      of a unique HCMV permissive macrophage phenotype as well as why virus is commonly
      reactivated in transplant patients.

PMID- 9774523
TI  - AF-DX 116, a presynaptic muscarinic receptor antagonist, potentiates the effects
      of glucose and reverses the effects of insulin on memory.
AB  - Male Swiss mice were tested 24 h after training in a one-trial step-through
      inhibitory avoidance task. Low subeffective doses of d-(+)-glucose (10 mg/kg,
      ip), but not its stereoisomer l-(-)-glucose (30 mg/kg,ip), administered
      immediately after training, and AF-DX 116 (0.3 mg/kg,ip), a presynaptic
      muscarinic receptor antagonist, given 10 min after training, interact to improve
      retention. Insulin (8 IU/kg, ip) impaired retention when injected immediately
      after training, and the effects were reversed, in a dose-related manner, by AF-DX
      116 (0.3, 1.0, or 3.0 mg/kg, ip) administered 10 min following insulin. Since AF
      DX 116 possibly blocks autoreceptors mediating the inhibition of acetylcholine
      release from cholinergic nerve terminals, the present data support the view that
      changes in the central nervous system glucose availability, subsequent to
      modification of circulating glucose levels, influence the activity of central
      cholinergic mechanisms involved in memory storage of an inhibitory avoidance
      response in mice.

PMID- 9774524
TI  - Individual differences in spatial memory and striatal ChAT activity among young
      and aged rats.
AB  - Individual differences in spatial memory among young and aged rats were assessed
      using memory tasks related to integrity of the hippocampus and the neostriatum.
      Relationships were then examined between measures of spatial memory and regional
      choline acetyltransferase (ChAT) activity, a marker for cholinergic integrity.
      Twenty-four-month-old Long-Evans rats were impaired in comparisons with 6-month
      old rats on measures of place learning, working memory, reference memory, and
      perseveration in water-maze tasks. Aged rats that were impaired on one measure of
      memory, however, were not necessarily impaired on other measures. ChAT activity
      in the ventromedial and dorsolateral neostriatum of aged rats was significantly
      reduced in comparisons with young rats whereas no difference was found in the
      hippocampus. Aged rats with the most ChAT activity in the anterior ventromedial
      neostriatum performed best on the place-learning and reference memory tasks but
      also made the most perseverative errors on the working memory task. In addition,
      young and aged rats with the most ChAT activity in the anterior dorsolateral
      neostriatum were those with the least accurate working memory. No relationships
      were found between ChAT activity in the hippocampus and spatial memory. Thus age
      related memory impairment has components that can be segregated by measuring
      relationships between cholinergic integrity in subregions of the anterior
      neostriatum and memory tasks with different strategic requirements.

PMID- 9774525
TI  - Memory for duration: role of hippocampus and medial prefrontal cortex.
AB  - In this task rats had to learn that a three-dimensional object stimulus (a
      rectangle) that was visible for 2 s would result in a positive (go) reinforcement
      for one object (a ball) and no reinforcement (no go) for a different object (a
      bottle). However, if the rectangle stimulus was visible for 8 s then there would
      be no reinforcement for the ball (no go), but a reinforcement for the bottle
      (go). After rats learned this conditional discrimination by responding
      differentially in terms of latency to approach the object, they received large
      (dorsal and ventral) lesions of the hippocampus, lesions of the medial prefrontal
      cortex (anterior cingulate and precentral cortex), lesions of the cortex dorsal
      to the dorsal hippocampus, or served as sham-operated controls. Following
      recovery from surgery they were retested. The results indicate that there were
      major impairments following hippocampal lesions, in contrast to cortical control
      and medial prefrontal cortex lesions, as indicated by smaller latency differences
      between positive and negative trials on postsurgery tests. In order to ensure
      that the deficits observed with hippocampal lesions were not due to a
      discrimination problem, new rats were trained in an object (gray cylinder)
      duration discrimination task. In this go/no go procedure, the rats were
      reinforced for a 2-s exposure (duration) of the gray cylinder, but not a 10-s
      duration, or vice versa. The results indicate that after hippocampal lesions,
      there was an initial deficit followed by complete recovery. There were no
      significant changes for the medial prefrontal, cortical control, or sham-operated
      animals. It appears that the hippocampus, but not the medial prefrontal cortex,
      is actively involved in representing in short-term memory temporal attribute
      information based on the use of markers for the beginning and end of the presence
      (duration) of a stimulus (object).

PMID- 9774526
TI  - Effects of posttraining intrahippocampal injections of platelet-activating factor
      and PAF antagonists on memory.
AB  - The present experiments examined the effects of posttraining intrahippocampal
      injections of the degradative enzyme-resistant methylcarbamyl analog of the
      bioactive phospholipid platelet-activating factor (mc-PAF) and the platelet
      activating factor (PAF) receptor antagonists BN52021 and BN 50730 on memory in
      male Long-Evans rats trained in a hidden platform version of the Morris water
      maze. Following an eight-trial training session, rats received a unilateral
      intrahippocampal injection of mc-PAF (0.5, 1.0, or 2.0 microgram/0.5 microliter),
      lyso-PAF (1.0 microgram/0.5 microliter), the cell surface PAF receptor antagonist
      BN 52021 (0.25, 0.5, or 1.0 micrigram/0.5 microliter/, the intracellular PAF
      receptor antagonist BN 50730 (2.0, 5.0, or 10.0 microgram/0.5 microliter), or
      vehicle (50% DMSO in 0.9% saline; 0.5 microliter). On a retention test conducted
      24 h after training, the escape latencies of rats administered mc-PAF (1.0 or 2.0
      microgram) were significantly lower than those of the vehicle-injected controls,
      demonstrating a memory-enhancing effect of mc-PAF. Injections of lyso-PAF, a
      structurally similar metabolite of PAF, had no influence on memory, indicating
      that the memory-enhancing effect of mc-PAF is not caused by membrane perturbation
      by the phospholipid. The retention test escape latencies of rats administered BN
      52021 (0.5 microgram) and BN 50730 (5.0 or 10 microgram) were significantly
      higher than those of the controls, indicating a memory impairing effect of both
      PAF antagonists. When mc-PAF, BN 52021, or BN 50730 was administered 2 h
      posttraining, no effect on retention was observed, indicating a time-dependent
      effect of the neuroactive substances on memory storage. The findings suggest a
      role for endogenous PAF in hippocampal-dependent memory processes.

PMID- 9774527
TI  - Posttraining electrical stimulation of vagal afferents with concomitant vagal
      efferent inactivation enhances memory storage processes in the rat.
AB  - Peripherally administered or released substances that modulate memory storage,
      but do not freely enter the brain, may produce their effects on memory by
      activating peripheral receptors that send messages centrally through the vagus
      nerve. Indeed, vagus nerve stimulation enhances memory performance, although it
      is unclear whether this effect is due to the activation of vagal afferents or
      efferents. To eliminate the possible influence of descending fibers on memory
      storage processes, rats were implanted with cuff electrode/catheter systems along
      the left cervical vagus. Forty-eight hours following surgery, each animal
      received a 3. 0-microliter infusion (1.0 microliter/min) of either lidocaine
      hydrochloride (75.0 mM) or isotonic saline below the point of stimulation.
      Animals were then trained 10 min later on an inhibitory-avoidance task with a
      0.75-mA, 1.0-s foot shock. Sham stimulation or vagus nerve stimulation (0.5-ms
      biphasic pulses; 20.0 Hz; 30 s; 0.2, 0.4, or 0.8 mA) was administered immediately
      after training. Memory, tested 24 h later, was enhanced by stimulation whether
      descending vagus nerve fibers were inactivated or not. Both lidocaine- and saline
      infused groups showed an intensity-dependent, inverted-U-shaped pattern of
      retention performance, with the greatest effect observed for 0.4 mA (U = 9, p <
      .05, and U = 7, p < .01, respectively). Additionally, animals that received
      lidocaine infusions, but no vagus nerve stimulation, showed impaired memory
      compared to the performance of saline-infused control animals (U = 11, p < .05).
      Together, these findings suggest that vagal afferents carry messages about
      peripheral states that lead to the modulation of memory storage and that the
      memory-enhancing effect produced by vagus nerve stimulation is not mediated via
      the activation of vagal efferents.

PMID- 9774528
TI  - Physostigmine's impact on brief shock-induced hypoalgesia parallels its effect on
      memory.
AB  - Past research indicates that the anticholinergic drug scopolamine disrupts memory
      and environmentally induced hypoalgesia in rats. The present study examined the
      impact of the centrally active cholinesterase inhibitor physostigmine, which
      enhances memory and central cholinergic activity, on brief shock-induced
      hypoalgesia on the tail-flick test using Sprague-Dawley rats. It is reported that
      physostigmine (0.1 mg/kg) potentiates the magnitude of this hypoalgesia. Contrary
      to past research, our results showed that omission of baseline testing did not
      eliminate hypoalgesia or its potentiation by physostigmine. Similar to its
      effects on memory, physostigmine (0.04, 0.1, and 0.25 mg/kg) has a nonmonotonic
      impact on brief shock-induced hypoalgesia; low doses potentiated hypoalgesia (0.1
      mg/kg), whereas a high dose (0.25 mg/kg) disrupted it. These results provide
      further evidence that the cholinergic system indirectly affects pain reactivity
      by modulating the memory of the aversive event.

PMID- 9774529
TI  - Cumulative subject index for volumes 69-70 

PMID- 9774530
TI  - Adaptations of a tropical swamp worm, alma emini, for subsistence in a H2S-rich
      habitat: evolution of endosymbiotic bacteria, sulfide metabolizing bodies, and
      novel processes of elimination of neutralized sulfide complexes 
AB  - The epithelial cell lining of the respiratory groove of Alma emini, an
      oligochaete glossoscolecid worm that lives in a hydrogen sulfide (H2S)-rich
      tropical swamp, was investigated by transmission electron microscopy to determine
      the underlying structural adaptations which enable the worm to subsist in a
      highly inimical habitat. The epithelium of the respiratory groove is made up of
      squamous cells with a highly amplified free epithelial surface. The cells are
      tightly packed with electron dense sulfur metabolizing bodies (SMBs) and contain
      endosymbiotic bacteria. Presence of sulfur in the electron dense SMBs was
      confirmed by X-ray microanalysis. Certain eukaryotic cells with prominent
      filopodia-like cytoplasmic extensions were observed under the epithelial cells
      and in the muscle tissue. The cells contained numerous heteromorphic
      endosymbiotic bacteria and scattered SMBs. Both the SMBs and the bacteria are
      reckoned to be involved in scavenging and detoxifying H2S. The removal of sulfide
      complexes was observed to occur through excision of blebs formed by epithelial
      cell membrane elaborations and by exocytosis of crystalline-like particles. These
      adaptive stratagems generally correspond with those that have been adopted by
      many marine and hydrothermal vent organisms that occupy sulfide-rich biomes. The
      congruent adaptive stratagems and ultrastructural morphologies in such a diverse
      community of organisms have been imposed by a common need to neutralize the
      insidious effects of H2S in their environments. Copyright 1998 Academic Press.

PMID- 9774531
TI  - Helical perturbations of the flagellar filament: rhizobium lupini H13-3 at 13 A
      resolution 
AB  - Flagellar filaments are highly conserved structures in terms of the underlying
      symmetry of the polymer, subunit domain organization of the flagellin monomer,
      amino acid composition and primary sequence at the N and C termini.
      Traditionally, filaments are classified as "plain" or "complex." In complex
      filaments, the helical lattice is perturbed in a pairwise manner such that the
      symmetry is reduced along the 6-start helical lines. Both plain (unperturbed) and
      complex (helically perturbed) components are helically symmetric and share a
      common lattice. The perturbation in Rhizobium lupini H13-3 results in a subunit
      composed of a dimer of flagellin. We have generated a approximately 13 A
      resolution three-dimensional density map of the complex filament of R. lupini H13
      3 from low-dose images of negatively stained filaments. Compared to a previous
      map, which extended to only approximately 25 A resolution and which was generated
      from only five filaments containing six layer-lines each, the current map is a
      product of merging 139 data sets containing 66 layer-lines each. The higher
      resolution and improved signal-to-noise yield a detailed and interpretable
      density map. The density map is divided into four concentric rings. These amount
      to two dense cylinders interconnected by low density radial spokes and wrapped by
      a three-start external winding. The unperturbed component of the map is
      strikingly similar to the known plain filament maps and, in particular, to that
      of Caulobacter crescentus. The helically perturbed component contributes mainly
      to the filaments's exterior (domain D3) where it comprises the tips of the outer
      domains interconnecting, pairwise, along the 11-start protofilaments and, again,
      laterally along the 6-start lines forming vertical and horizontal loops. Strong
      intersubunit connectivity occurs in the D2 shell and in the inner shell which is
      dominated by 3-start densities. The contribution of the complex component to the
      radial spokes seems negligible. Copyright 1998 Academic Press.

PMID- 9774532
TI  - The organization of actin in the apical region of insect midgut cells after deep
      etching 
AB  - The midgut of Tenebrio larvae, which reveals a strong reaction for F-actin
      beneath the apical microvilli after rhodamine-phalloidin treatment, was studied
      to examine localization of actin. Freeze-fracture replicas of the lateral midgut
      borders reveal that smooth septate junctions with their characteristic rows of
      aligned intramembranous particles (IMPs) are found on the upper third of these
      borders. Thin sections show that short punctate adhering junctions may also occur
      on this part of the border. Deep etching reveals that the rows of septate
      junctional IMPs are closely juxtaposed to cytoplasmic fibrils that demonstrate
      the structural features typical of actin as well as heavy meromyosin labeling.
      These actin fibrils appear to insert into the junctional membranes. Hence
      cytoskeletal elements have an intimate spatial association with the membrane
      modifications typical of intercellular septate junctions and may be involved in
      the positioning of their component IMPs and also possibly of their septal
      ribbons. Copyright 1998 Academic Press.

PMID- 9774533
TI  - Crystallization and preliminary X-Ray diffraction analysis of the 190-A-long
      coiled-coil dimerization domain of the actin-bundling protein cortexillin I from
      dictyostelium discoideum 
AB  - We have crystallized the approximately 190-A-long parallel two-stranded coiled
      coil oligomerization domain of the actin-bundling protein cortexillin I from
      Dictyostelium discoideum. The orthorhombic crystals belong to the space group
      C2221 with unit cell dimensions of a = 71.3 A, b = 127.8 A, and c = 91.6 A. As
      both native and selenomethionine-substituted protein crystals diffract to 3.0 and
      2.85 A resolution, respectively, using synchrotron radiation, they are suitable
      for the first high-resolution structural analysis of a two-stranded coiled coil
      comprising more than six heptad repeats. Moreover, because the polypeptide chain
      fragment contains a recently identified two-heptad-repeat long sequence that is
      indispensable for the assembly of the cortexillin I coiled-coil oligomerization
      domain, its high-resolution structure should enable us to extend our knowledge on
      the molecular mechanisms underlaying coiled-coil formation and to establish the
      precise manner in which the two "trigger" sequences interact with one another in
      the dimer. Copyright 1998 Academic Press.

PMID- 9774534
TI  - Structural changes of surfactant protein A induced by cations reorient the
      protein on lipid bilayers.
AB  - Surfactant protein A (SP-A) is an octadecameric hydrophilic glycoprotein and is
      the major protein component of pulmonary surfactant. This protein complex plays
      several roles in the body, such as regulation of surfactant secretion, recycling
      and adsorption of surfactant lipids, and non-serum-induced immune response. Many
      of SP-A's activities are dependent upon the presence of cations, especially
      calcium. Here, we have studied in vitro the effect of cations on the interaction
      of purified bovine SP-A with phospholipid vesicles made of
      dipalmitoylphosphatidylcholine and unsaturated phosphatidylcholine. We have found
      that SP-A octadecamers exist in an "opened-bouquet" conformation in the absence
      of cations and interact with lipid membranes via one or two globular headgroups.
      Calcium-induced structural changes in SP-A lead to the formation of a clearly
      identifiable stem in a "closed-bouquet" conformation. This change, in turn,
      seemingly results in all of SP-A's globular headgroups interacting with the lipid
      membrane surface and with the stem pointing away from the membrane surface. These
      results represent direct evidence that the headgroups of SP-A (comprising
      carbohydrate recognition domains), and not the stem (comprising the amino
      terminus and collagen-like region), interact with lipid bilayers. Our data
      support models of tubular myelin in which the headgroups, not the tails, interact
      with the lipid walls of the lattice.

PMID- 9774535
TI  - Architectural features of the Salmonella typhimurium flagellar motor switch
      revealed by disrupted C-rings.
AB  - The three-dimensional surface topology of rapid-frozen Salmonella typhimurium
      flagellar hook basal body complexes was studied by stereo-examination of thin
      film metal replicas. The complexes contained the extended cytoplasmic structure,
      composed of the switch complex proteins; FliG, FliM, and FliN. Distinct nanometer
      scale element arrays, separated by grooves, defined the outer surface of the
      cytoplasmic (C-) ring. The number of array elements was comparable to previously
      determined FliG and FliM copy numbers in the basal body. In addition to basal
      body complexes lacking C-rings, complexes containing incomplete C-rings were
      identified. The incomplete C-rings had lost segments of the proximal array. Basal
      bodies with the distal C-ring array alone were not found. These findings are
      compatible with the spatial organization of the flagellar switch suggested by
      previous biochemical data.

PMID- 9774536
TI  - Temperature and pH-dependent supramolecular self-assembly of amelogenin
      molecules: a dynamic light-scattering analysis.
AB  - Evidence for the molecular self-assembly of amelogenin proteins to form quasi
      spherical particles ("nanospheres") in solution, both in vitro and in vivo, has
      recently been documented. A particle-size distribution analysis of dynamic light
      scattering data was undertaken to investigate the influence of temperature on
      this molecular self-assembly process at three different pH's. The long-term
      objective was to correlate these observations to the unusual physiochemical
      characteristics of the protein, to improve understanding of the molecular
      mechanisms involved in the generation of amelogenin "nanospheres" and
      understanding of their putative relation to amelogenin function in vivo. We
      analyzed data using two different algorithms: Dynamics and DynaLS. It was found
      that at pH 8, in a temperature range between 5 and 25 degrees C, the size of the
      recombinant amelogenin nanospheres is monodisperse, giving rise to particles of
      15-18 nm in hydrodynamic radius. However, heterogeneous distribution of particle
      size was observed at temperature ranges between 27 and 35 degrees C, becoming
      monodisperse again with larger particles (60-70 nm) after the temperature was
      elevated to 37-40 degrees C. We interpret these results to suggest that
      amelogenin molecular self-association possesses a second stage assembly process
      at temperatures of 30-35 degrees C, creating larger entities which apparently are
      structured and stable at 37-40 degreesC. The effect of pH on the size of
      amelogenin "aggregates" was much more noticeable at 37 degrees C compared to that
      at 25 degrees C. This observation suggests that at physiological temperature
      (i.e., 37 degrees C) amelogenin molecular self-assembly is extremely sensitive to
      pH changes. This finding supports the notion that local pH changes in the
      microenvironment of the enamel extracellular matrix may play critical roles in
      controlling the structural organization of the organic matrix framework.

PMID- 9774537
TI  - A maximum-likelihood approach to single-particle image refinement.
AB  - The alignment of single-particle images fails at low signal-to-noise ratios and
      small particle sizes, because noise produces false peaks in the cross-correlation
      function used for alignment. A maximum-likelihood approach to the two-dimensional
      alignment problem is described which allows the underlying structure to be
      estimated from large data sets of very noisy images. Instead of finding the
      optimum alignment for each image, the algorithm forms a weighted sum over all
      possible in-plane rotations and translations of the image. The weighting factors,
      which are the probabilities of the image transformations, are computed as the
      exponential of a cross-correlation function. Simulated data sets were constructed
      and processed by the algorithm. The results demonstrate a greatly reduced
      sensitivity to the choice of a starting reference, and the ability to recover
      structures from large data sets having very low signal-to-noise ratios.

PMID- 9774538
TI  - Immuno-cross-reactivity of CUT-1 and cuticlin epitopes between ascaris
      lumbricoides, Caenorhabditis elegans, and Heterorhabditis.
AB  - Cuticlin is the insoluble residue of nematode cuticle. It has been proved that
      cuticlin and CUT-1-like epitopes are conserved between the free-living
      Caenorhabditis elegans and the entomopathogenic nematode Heterorhabditis sp. The
      cloning of a cut-1 homologous gene from the animal intestinal parasite Ascaris
      lumbricoides has allowed us to extend the study of immuno-cross-reactivity at the
      ultrastructural level to this important species. Antibodies against recombinant
      CUT-1 protein and against cuticlin from Ascaris as well as from C. elegans were
      used for immuno-labeling ultrathin sections of high-pressure cryoprocessed worms.
      All the antisera used showed the same specific pattern of localization on
      sections of C. elegans of Heterorhabditis dauer larvae, and of Ascaris larvae in
      mature eggs. It was also shown that sera raised against the cuticlin residue
      contain anti-CUT-1 antibodies. CUT-1-like proteins are thus possibly important
      components in the immune response of hosts to invading nematodes. The results
      presented support the use of C. elegans as a model for the study of vertebrate
      parasitic nematodes.

PMID- 9774539
TI  - Electron microscopic observation of monomeric actin attached to a myosin head.
AB  - Attachment of G-actin to a myosin head was for the first time visualized by
      electron microscopy of heavy meromyosin (HMM) molecules decorated using a
      chemical crosslinker with G-actin, which is made resistant to salt- and myosin
      induced polymerization by treatment with m-maleimidobenzoic acid N
      hydroxysuccinimide ester (MBS). Rotary-shadowed images of acto-HMM molecules
      crosslinked using MBS or water-soluble carbodiimide showed that MBS-G-actin binds
      to the distal half of a myosin head (the region 14-15 nm away from the head-rod
      junction).

PMID- 9774540
TI  - QVIEW: software for rapid selection of particles from digital electron
      micrographs.
AB  - The QVIEW image-processing software package provides a graphical user interface
      for interactive and rapid selection of particles from digital electron
      micrographs. This package was developed to facilitate the selection of
      elliptical, hydrophobic, and aggregating particles, which present complications
      for other particle selection packages. Speed improvements have been attained by
      using the fast graphics routines available in the Tc1/Tk toolkit and by
      separating the time consuming image-processing procedures from the interactive
      selection steps. The software is based on C++ and Tc1/Tk, both of which are
      readily available on many computer platforms. Processing features include removal
      of oversaturated pixels, planar subtraction using three or more background
      regions, exclusion of unwanted density such as nearby particles, and application
      of a circular or elliptical mask. Particles, along with their corresponding
      background and exclude regions, may be selected interactively from multiple
      digital micrographs, and the selection parameters are saved in a disk file for
      later processing. C shell processing scripts are easily modified and customized
      for specific applications. In summary, this software package enables the user
      friendly, rapid selection of particles suitable for input into three-dimensional
      reconstruction packages.

PMID- 9774541
TI  - Crystal packing induces a conformational change in profilin-I from Acanthamoeba
      castellanii.
AB  - Profilin-I from Acanthamoeba castellanii is a 13-kDa protein that binds actin and
      poly-l-proline. The native protein has been crystallized in two different but
      closely related forms. The second form proved more amenable to three-dimensional
      structural determination using heavy-atom isomorphous methods to obtain
      crystallographic phase information. We used the second crystal structure as a
      test molecule in the molecular replacement procedure to determine the structure
      of the first crystal form of profilin-I. More residues participate in crystal
      lattice contacts in the first crystal form than in the second. The two crystal
      forms differ significantly in the C-terminal helix that interacts with actin and
      in the loop preceding this helix. Coordinates of some main chain atoms here
      differ by about 1.0 A, and side chain atoms differ by more than 2.0 A.

PMID- 9774542
TI  - Two-dimensional crystallization of the chaperonin TF55 from the hyperthermophilic
      archaeon Sulfolobus solfataricus.
AB  - Oligomers of the chaperonin TF55 from Sulfolobus solfataricus have been
      successfully crystallized in two dimensions via their interaction with a
      phospholipid monolayer at the air/liquid interface. Oligomer orientation was
      dependent upon the lipid headgroup used. A neutral lipid monolayer gave rise to
      small paracrystalline areas of TF55 side views, whereas a negatively charged
      lipid monolayer resulted in large coherent crystalline areas of the chaperonin in
      an end-on orientation. These 2D crystals had p312 symmetry (a = b = 162 A, gamma
      = 60 degrees). Two-dimensional projection structures of the end-on arrays were
      produced by electron microscopy and image processing techniques. Under the
      conditions used to grow the crystals, the protein formed complexes of two stacked
      nine-subunit rings with threefold symmetry.

PMID- 9774543
TI  - Reconstitution and imaging of a membrane protein in a nanometer-size phospholipid
      bilayer.
AB  - A phospholipid bilayer of nanometer dimension has been used as a support for the
      study of reconstituted functional single-membrane proteins. This nanobilayer
      consists of an approximately 10-nm-diameter circular phospholipid domain
      stabilized by apolipoprotein A1. As a demonstration of this methodology, we
      formed the nanobilayers in the presence of hepatic microsomal NADPH-cytochrome
      P450 reductase. Incubation of a solution of enzyme-containing nanobilayers with a
      freshly cleaved mica substrate resulted in the spontaneous formation of a fully
      oriented supported monolayer of discoidal phospholipid domains. The P450
      reductase in the oriented monolayer retains its catalytic activity.
      Characterization by scanning force microscopy revealed isolated single-membrane
      proteins that could be stably imaged over time. These results define a novel
      technique for the study of single-membrane proteins in a bilayer environment.

PMID- 9774544
TI  - A fast-freezing device with a retractable environmental chamber, suitable for
      kinetic cryo-electron microscopy studies.
AB  - The design and construction of a fast-freezing device are described. A
      polycarbonate chamber, in which the humidity and temperature are controlled by
      microprocessors, slides on a robust chassis guided by ball or Teflon bushings. In
      its freezing position, the chamber rests on top of the cryogen vessel. The
      specimen is therefore frozen directly from the experimental conditions within the
      chamber without exposure to the external environment. After freezing, the
      chamber, but not the specimen, rises automatically, vacating space for handling
      the specimen. The chamber, the shutter, and the specimen are all driven
      pneumatically at an adjustable speed of up to approximately 10 m s-1 and
      coordinated by either pneumatic or electronic logical gates. Provisions are made
      for automatic blotting, spraying, and flashing. The chamber is compatible with a
      liquid nitrogen-cooled copper block assembly for impact (slam) freezing for
      freeze-substitution and freeze-fracture.

PMID- 9774545
TI  - A tailless Drosophila lamin Dm0 fragment reveals lateral associations of dimers.
AB  - An early step in nuclear lamin polymerization is the longitudinal, head-to-tail
      association of lamin dimers through the highly conserved end segments of their
      rod domains. Lamin fragments lacking the carboxy-terminal tail domain (tailless
      lamins) form long, thin protofilaments more readily than full-length lamins do.
      By morphology alone it cannot be ascertained whether tailless lamin
      protofilaments also arise through head-to-tail association of dimers. Here, we
      studied by transmission electron microscopy which types of interaction are
      important for formation of protofilaments by a tailless lamin fragment derived
      from Drosophila lamin Dm0. First, we measured the lengths of tailless lamin
      filaments shorter than 200 nm. Many particles were longer than one and shorter
      than two dimers. Second, we labeled filaments formed by tailless lamin with a Fab
      fragment derived from a monoclonal antibody binding to an epitope residing in the
      amino-terminal head domain. The pattern of Fab fragments bound to lamin filaments
      clearly showed that most tailless lamin dimers are not arranged in a head-to-tail
      fashion. Third, we mutated tailless lamin using two point mutations known to
      inhibit head-to-tail association of full-length lamin. Thus mutated tailless
      lamin still formed filaments. We interpret these data according to models
      involving lateral associations between dimers of cytoplasmic intermediate
      filament proteins, using the lengths of short tailless lamin filaments as
      constraints. The data also demonstrate that a segment of at most 41 amino acids
      of the lamin tail domain is sufficient to bring about the change of mainly
      lateral to mainly longitudinal assembly.

PMID- 9774546
TI  - A 7.4-A projection structure of outer membrane phospholipase A from Escherichia
      coli by electron crystallography.
AB  - Outer membrane phospholipase A (OMPLA) is one of the few enzymes present in the
      outer membrane of Escherichia coli. Two-dimensional crystals of OMPLA were grown
      by reconstitution of purified protein into lipid bilayers via detergent dialysis
      and were studied by electron crystallography. A 7.4-A projection map reveals
      OMPLA molecules exhibiting an oval-shaped domain of 30 x 20 A resembling the beta
      barrel structure characteristic of porins, which is associated with a 25-A
      elongated domain of lower density.

PMID- 9774547
TI  - Visualization of cytoskeletal elements in the transmission X-ray microscope.
AB  - Transmission X-ray microscopy has been used to study the arrangement of
      cytoskeletal filaments in interphase PtK2 cells. Extraction of the soluble
      proteins and of some organelles with the nonionic detergent Triton X-100 was
      important in obtaining sufficient image contrast between the insoluble
      cytoskeletal filaments and the surrounding cytoplasm. If this step is not
      performed cytoskeletal filaments are not visualized and transmission X-ray
      micrographs of the cytoplasm instead show predominantly membrane-bound organelles
      such as vesicles and the endoplasmic reticulum. Transmission X-ray micrographs of
      the cytoskeletal filaments and endoplasmic reticulum in air-dried specimens, as
      well as in specimens examined in the wet state, can be directly compared with
      transmission electron micrographs of cytoskeletons prepared in the same way. The
      profiles seen with the two techniques are similar, although, currently,
      transmission X-ray micrographs have a limit of resolution of approximately 50 nm.
      Transmission X-ray micrographs appear to show some substructure in interphase
      nuclei in cells fixed either with glutaraldehyde or by cryofixation and examined
      in a hydrated condition.

PMID- 9774548
TI  - Preliminary crystallographic study of glutathione S-transferase fused with the
      nuclear matrix targeting signal of the transcription factor AML-1/CBF-alpha2.
AB  - A glutathione S-transferase fused with the nuclear matrix targeting signal (GST
      NMTS) of AML-1/CBF-alpha2 has been crystallized by the vapor diffusion method
      using polyethylene glycol (PEG) as the precipitant. The NMTS is a 31-amino-acid
      signal peptide that can target the AML-1/CBF-alpha2 protein to the nuclear
      matrix. The crystal belongs to tetragonal space group P43212 with unit cell
      dimensions a = b = 93.4 A, c = 57.6 A. There is one GST-fusion protein per
      asymmetric unit. Crystals diffracted to at least 2.7 A and are appropriate for
      structure determination.

PMID- 9774549
TI  - Cutaneous aspergillosis.

PMID- 9774550
TI  - Urine specimens from pregnant and nonpregnant women inhibitory to amplification
      of Chlamydia trachomatis nucleic acid by PCR, ligase chain reaction, and
      transcription-mediated amplification: identification of urinary substances
      associated with inhibition and removal of inhibitory activity.
AB  - The presence of endogenous amplification inhibitors in urine may produce false
      negative results for the detection of Chlamydia trachomatis nucleic acids by
      tests such as PCR, ligase chain reaction (LCR), and transcription-mediated
      amplification (TMA). Consecutive urine specimens from 101 pregnant women and 287
      nonpregnant women submitted for urinalysis were processed for C. trachomatis
      detection. Aliquots were spiked with the equivalent of one C. trachomatis
      elementary body and were tested by three commercial assays: AMPLICOR CT/NG,
      Chlamydia LCX, and Chlamydia TMA. The prevalence of inhibitors resulting in
      complete inhibition of amplification was 4.9% for PCR, 2.6% for LCR, and 7.5% for
      TMA. In addition, all three assays were partially inhibited by additional urine
      specimens. Only PCR was more often inhibited by urine from pregnant women than by
      urine from nonpregnant women (9.9 versus 3.1%; P = 0.011). A complete urinalysis
      including dipstick and a microscopic examination was performed. Logistic
      regression analysis revealed that the following substances were associated with
      amplification inhibition: beta-human chorionic gonadotropin (odds ratio [OR],
      3.3) and crystals (OR, 3.3) for PCR, nitrites for LCR (OR, 14.4), and hemoglobin
      (OR, 3.3), nitrites (OR, 3.3), and crystals (OR, 3.3) for TMA. Aliquots of each
      inhibitory urine specimen were stored at 4 and -70 degreesC overnight or were
      extracted with phenol-chloroform and then retested at dilutions of 1:1, 1:4, and
      1:10. Most inhibition was removed by storage overnight at 4 or -70 degreesC and a
      dilution of 1:10 (84% for PCR, 100% for LCR, and 92% for TMA). Five urine
      specimens (three for PCR and two for TMA) required phenol-chloroform extraction
      to remove inhibitors. The results indicate that the prevalence of nucleic acid
      amplification inhibitors in female urine is different for each technology, that
      this prevalence may be predicted by the presence of urinary factors, and that
      storage and dilution remove most of the inhibitors.

PMID- 9774551
TI  - Genospecies identification and characterization of Lyme disease spirochetes of
      genospecies Borrelia burgdorferi sensu lato isolated from rodents in Taiwan.
AB  - Lyme disease spirochetes of the genospecies Borrelia burgdorferi sensu lato were
      identified and characterized for the first time in Taiwan. Seven isolates,
      designated TWKM1 to TWKM7, were purified from the ear tissues of three species of
      rodents captured from seven localities of Taiwan. The immunological
      characteristics of these Taiwan isolates were compared with those of other
      genospecies of Lyme disease spirochetes by analyzing the protein profiles and
      reactivities with B. burgdorferi-specific monoclonal antibodies (MAbs). The
      genospecies of these Taiwan isolates were also identified by the similarities in
      their plasmid profiles and differential reactivities with genospecies-specific
      PCR primers. Although two distinct protein profiles were observed among the seven
      Taiwan isolates, the MAb reactivities against the outer surface proteins of B.
      burgdorferi of all of these isolates were consistent with those of B. burgdorferi
      sensu lato. The similarities of the plasmid profiles also confirmed the
      identities of these Taiwan isolates. PCR analysis indicated that all of these
      Taiwan isolates were genetically related to the genospecies B. burgdorferi sensu
      stricto. These results demonstrate the first identification of Lyme disease
      spirochetes in Taiwan and also highlight the increasing demand for defining the
      reservoirs and vector ticks of B. burgdorferi. A serosurvey for Lyme disease
      infection in the human population of Taiwan may also be required.

PMID- 9774552
TI  - Fluorescent amplified-fragment length polymorphism analysis of an outbreak of
      group A streptococcal invasive disease.
AB  - Fluorescent amplified-fragment length polymorphism (FAFLP) analysis was carried
      out for an outbreak of group A streptococcal (GAS) invasive disease.
      Streptococcal genomic DNAs were digested with endonucleases EcoRI and MseI, site
      specific adaptors were ligated, and PCR amplification was carried out with an
      EcoRI adaptor-specific primer labelled with fluorescent dye. Amplified fragments
      of up to 600 bp in size were separated on a polyacrylamide sequencing gel which
      contained internal size markers in each lane. These data were automatically
      scanned and analyzed, fragments were precisely sized (+/-1 bp), and
      electropherograms were generated for each genome with GeneScan 2.1 software. All
      isolates were compared in this way. Among 27 GAS isolates examined, we found 18
      FAFLP profiles, compared with 12 macrorestriction profiles by pulsed-field gel
      electrophoresis. FAFLP readily distinguished genotypes for two clones of GAS
      serotype M77 which were responsible for outbreaks of invasive disease in a care
      of-the-elderly system. It provided an automated analysis of the whole genome of
      bacterial isolates. It was reproducible, more discriminatory, and capable of
      higher throughput than other molecular typing methods. Given agreed conditions,
      FAFLP would be reproducible between laboratories for rapid characterization of
      outbreak strains.

PMID- 9774553
TI  - Macroscopic agglutination test for rapid diagnosis of human leptospirosis.
AB  - A commercially available slide agglutination test (SAT) for the diagnosis of
      human leptospirosis was evaluated by comparing it to an immunoglobulin M (IgM)
      enzyme-linked immunosorbent assay (ELISA) and to the microscopic agglutination
      test (MAT). For all 108 patients, leptospirosis was diagnosed on the basis of a
      fourfold or greater increase in titer by MAT (seroconversion), and all but 1 of
      245 controls were MAT negative (titers, <1:100). Both SAT and the IgM ELISA
      failed to detect one case of infection (sensitivity, 99%). Only 3 of 145 blood
      donors and none of the 100 patients with other illnesses were SAT positive
      (specificity, 99%). The overall results were similar for the three tests;
      however, SAT and ELISA were statistically more sensitive as initial screening
      tests. For 22% of the patients, the diagnosis of leptospirosis was made earlier
      by SAT than by MAT. SAT detected 27 (44%) of 62 MAT-negative patients with the
      first serum sample. ELISA and SAT had very similar results. Follow-up of patients
      for 1 year after the onset of symptoms showed a decreasing rate of positivity by
      SAT from the third month on. The rate of positivity by ELISA decreased more
      slowly, to about 67% by the end of the study. By MAT all patients were
      persistently reactive. SAT and ELISA seem to be convenient methods for the rapid
      and early screening for leptospirosis and could replace the less sensitive MAT.
      ELISA gives less subjective results than SAT and provides information on IgM
      kinetics, but it can be performed only by the more sophisticated laboratories.
      SAT is inexpensive, can be performed more quickly and more easily than ELISA, and
      could be used by the less well equipped laboratories.

PMID- 9774554
TI  - Detection of Lassa virus antinucleoprotein immunoglobulin G (IgG) and IgM
      antibodies by a simple recombinant immunoblot assay for field use.
AB  - The nucleoprotein of Lassa virus, strain Josiah, was expressed in Escherichia
      coli as an N-terminally truncated, histidine-tagged recombinant protein.
      Following affinity purification the protein was completely denatured and spotted
      onto nitrocellulose membrane. A total of 1 microgram of protein was applied for
      detection of Lassa virus antibodies (LVA) in a simple immunoblot assay. Specific
      anti-Lassa immunoglobulin M (IgM) antibodies could be detected by increasing the
      amount of protein to 5 microgram. A panel of 913 serum specimens from regions in
      which Lassa virus was endemic and from regions in which Lassa virus was not
      endemic was used for evaluating the sensitivity and specificity of the LVA
      immunoblot in comparison to those of an indirect immunofluorescence (IIF) assay.
      The sera originated from field studies conducted in the Republic of Guinea (570
      serum samples) and Liberia (99 serum samples), from inpatients of the clinical
      department of the Bernhard-Nocht-Institute, Hamburg, Germany (94 serum samples),
      and from healthy German blood donors (150 serum samples). In comparison to the
      IIF assay the LVA immunoblot assay had a specificity of 90.0 to 99.3%, depending
      on the origin of the specimens. The sensitivity was found to be highest for the
      Guinean samples (90.7%) and was lower for the Liberian samples (75%). Acute Lassa
      fever was diagnosed by PCR in 12 of 59 (20.3%) patients with fever of unknown
      origin (FUO) from the Republic of Guinea. On admission to the hospital, nine
      Lassa fever patients (75%) were reactive by the IgM immunoblot assay. One of the
      patients was infected with a new Lassa variant, which showed 10.4% variation on
      the amino acid level in comparison to the prototype strain of Lassa virus,
      Josiah. Seven PCR-negative patients were reactive by immunoblotting. The positive
      and negative predictive values of a single IgM immunoblot result for acute, PCR
      confirmed Lassa fever were therefore 53.6 and 93.0%, respectively. Because of its
      high negative predictive value, a single IgM immunoblot result will be valuable
      for excluding acute Lassa fever for cases of FUO in areas where Lassa fever is
      endemic.

PMID- 9774555
TI  - Direct detection of respiratory syncytial virus, parainfluenza virus, and
      adenovirus in clinical respiratory specimens by a multiplex reverse transcription
      PCR assay.
AB  - Diagnosis of respiratory virus infections currently involves detection by
      isolation or antigen detection, which usually identifies only a single suspected
      agent. To permit identification of more than one respiratory virus in clinical
      specimens, a rapid detection method involving a single-step, multiplex reverse
      transcription-PCR (RT-PCR) assay was developed. The assay included five primer
      sets that amplified the RNA of respiratory syncytial virus subtypes A and B,
      parainfluenza virus types 1, 2, and 3, and adenovirus types 1 to 7. Initially the
      assay was tested on tissue culture-grown virus and was found to be specific for
      all 12 prototype viruses tested, with no interassay cross amplification or
      amplification of other respiratory viruses. Assay sensitivity allowed a detection
      range of 0.2 50% tissue culture infectious dose (TCID50) for adenovirus to 250
      TCID50 for parainfluenza virus type 1. The multiplex RT-PCR assay was also able
      to directly detect viruses in respiratory specimens, with virus being detected in
      41 of 112 samples as compared to 34 of 112 samples detected by direct
      immunofluorescence or antigen detection following specimen culture. This suggests
      that the multiplex RT-PCR assay can be used as a rapid and sensitive diagnostic
      method for major respiratory viruses.

PMID- 9774556
TI  - Diagnosis of Mycoplasma pneumoniae pneumonia in children.
AB  - We evaluated a commercial immunoglobulin M (IgM)-capture immunoassay for the
      detection of Mycoplasma pneumoniae infections in 278 pediatric patients with
      community-acquired, radiographically defined pneumonia. Acute- and convalescent
      phase serum samples were collected from all patients and were tested for M.
      pneumoniae-specific IgM and IgG antibodies by Platelia enzyme immunoassays
      (Sanofi Diagnostica Pasteur, Marnes la Coquette, France). Nasopharyngeal
      aspirates (NPAs) were collected at the time of admission to the hospital. A total
      of 227 NPAs were subjected to the detection of M. pneumoniae DNA by PCR, and 191
      NPAs were cultured by using the Pneumofast kit (International Mycoplasma,
      Signeswere, France). Southern hybridization of PCR products and the IgM test with
      solid-phase antigen (Serion Immunodiagnostica, Wurzburg, Germany) were used for
      additional confirmation of a positive result, which required agreement of at
      least two different methods. A total of 24 (9%) confirmed diagnoses of mycoplasma
      infection were made, 5 (21%) of which were in children <5 years of age. Of the
      positive children, 24 of 24 (sensitivity, 100%) were positive by the IgM-capture
      test with convalescent-phase serum, 19 of 24 (79%) were positive by the IgM
      capture test with acute-phase serum, 19 of 24 (79%) were positive by IgG
      serology, 10 of 20 (50%) were positive by PCR, and 8 of 17 (47%) were positive by
      culture. An additional 5 (of 254) children were positive by the Platelia IgM test
      alone (specificity, 98%). When the PCR with Southern hybridization result was
      combined with the IgM-capture test result with the acute-phase sera, the
      sensitivity of rapid laboratory diagnosis increased to 95%. In conclusion, the
      IgM serology test was the single most valuable tool for the diagnosis of M.
      pneumoniae pneumonia in children of any age.

PMID- 9774558
TI  - Nucleic acid sequence-based amplification, a new method for analysis of spliced
      and unspliced Epstein-Barr virus latent transcripts, and its comparison with
      reverse transcriptase PCR.
AB  - Nucleic acid sequence-based amplification (NASBA) assays were developed for
      direct detection of Epstein-Barr virus (EBV) transcripts encoding EBV nuclear
      antigen 1 (EBNA1), latent membrane proteins (LMP) 1 and 2, and BamHIA rightward
      frame 1 (BARF1) and for the noncoding EBV early RNA 1 (EBER1). The sensitivities
      of all NASBAs were at least 100 copies of specific in vitro-generated RNA.
      Furthermore, 1 EBV-positive JY cell in a background of 50,000 EBV-negative Ramos
      cells (the relative sensitivity) was detected by using the EBNA1, LMP1, and LMP2
      NASBA assays. The relative sensitivity of the EBER1 NASBA was 100 EBV-positive
      cells, which was probably related to the loss of small RNA molecules during the
      isolation. The BARF1 and LMP2 NASBAs were evaluated on clinical material. BARF1
      expression was found in 6 of 7 nasopharyngeal carcinomas (NPC) but in 0 of 22
      Hodgkin's disease (HD) cases, whereas LMP2 expression was found in 7 of 7 NPCs
      and in 17 of 22 HD cases. For detection of EBNA1 transcripts in HLs (n = 12) and
      T- and B-cell non-Hodgkin's lymphomas (n = 3 and n = 2, respectively), NASBA was
      compared with reverse transcriptase (RT) PCR. Two samples were positive only with
      NASBA, and two other samples were positive only with RT-PCR; for all other
      samples, the RT-PCR and NASBA results were in agreement. We conclude that NASBA
      is suitable for sensitive and specific detection of the above-mentioned EBV
      transcripts, regardless of their splicing patterns and the presence of EBV DNA.
      The EBNA1, LMP2, and BARF1 NASBAs developed in this study proved to be reliable
      assays for detection of the corresponding transcripts in EBV-positive clinical
      material.

PMID- 9774557
TI  - Prevalence of human calicivirus infections in Kenya as determined by enzyme
      immunoassays for three genogroups of the virus.
AB  - An epidemiological survey on human calicivirus (HuCV) infections and associated
      gastroenteritis in infants was conducted to clarify the prevalence of HuCV
      infections in infants and adults in Kenya. Enzyme immunoassays (EIAs) for three
      genogroups of HuCVs, Norwalk virus (NV), Mexico virus (MXV), and Sapporo virus
      (SV), were used to detect antigen or antibody. We tested 1,431 stool samples
      obtained from children younger than 6 years old with acute gastroenteritis who
      visited outpatient clinics in three districts in Kenya from August 1991 to July
      1994. Thirty-two (2.2%) of these stool samples were positive for SV antigen. Only
      one (0.1%) of 1,186 samples was positive for NV antigen and none of 246 samples
      was positive for MXV antigen. One hundred ninety-three serum samples were tested
      for antibodies to NV and MXV, and 64 of them were examined for antibody to SV.
      The pattern of the age-related prevalence of serum antibody to NV was different
      from that of antibodies to MXV and SV. The acquisition of serum antibodies to
      HuCVs in the three genogroups appeared in early childhood, at about 1 to 2 years
      of age. The prevalence of serum antibody to NV was low (about 60%) throughout
      adulthood compared with a high prevalence of antibody (approximately 80 to 90%)
      to MXV and SV. These data indicate that infections with viruses in the three
      genogroups of HuCVs are common in Kenya, and immunological responses to NV may be
      different from those to MXV and SV. The EIAs for the detection of NV and MXV
      antigens appear to be quite specific for prototype NV and MXV strains,
      respectively, so that they can detect only a few strains of HuCVs related to
      them. Alternatively, NV and MXV caused less severe infections that did not bring
      children to the outpatient clinics for gastroenteritis in Kenya.

PMID- 9774559
TI  - Diagnostic potential of Toscana virus N protein expressed in Escherichia coli.
AB  - The nucleocapsid (N) protein of the Toscana (TOS) virus was expressed in
      Escherichia coli by using a pET15b vector. The recombinant protein was purified
      by affinity chromatography and was characterized by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, immunoblotting, and enzyme immunoassay (EIA).
      The recombinant antigen was reactive with positive human sera, and the reactivity
      correlated very well (r = 0.9) with that of a whole-virus antigen when tested by
      EIA with 30 TOS virus-positive and 30 TOS virus-negative serum samples. The
      results demonstrate that the recombinant N protein can be easily produced in a
      procaryotic system and used for diagnostic assays for TOS virus immunity.

PMID- 9774560
TI  - Comparison of phenotypic and genotypic methods for detection of diphtheria toxin
      among isolates of pathogenic corynebacteria.
AB  - We have compared molecular, immunochemical, and cytotoxic assays for the
      detection of diphtheria toxin from 55 isolates of Corynebacterium diphtheriae and
      Corynebacterium ulcerans originally isolated in five different countries. The
      suitabilities and accuracies of these assays for the laboratory diagnosis of
      diphtheria were compared and evaluated against the "gold standard" in vivo
      methods. The in vivo and Vero cell cytotoxicity assays were accurate in their
      abilities to detect diphtheria toxin but were time-consuming; however, the
      cytotoxicity assay is a suitable in vitro alternative to the in vivo virulence
      test. There was complete concordance between all the phenotypic methods.
      Genotypic tests based upon PCR were rapid; however, PCR must be used with caution
      because some isolates of C. diphtheriae possessed toxin genes but failed to
      express a biologically active toxin. Therefore, phenotypic confirmation of
      toxigenicity for the microbiological diagnosis of diphtheria is recommended.

PMID- 9774561
TI  - Enzyme-linked immunosorbent assay based on recombinant human group C rotavirus
      inner capsid protein (VP6) To detect human group C rotaviruses in fecal samples.
AB  - A recent study showed that 43% of a population in the United Kingdom were
      seropositive for group C rotavirus. The higher than expected incidence may be due
      to limited diagnosis of acute human group C rotavirus infections because no
      routine test is available. Human group C rotavirus infections are routinely
      diagnosed by electron microscopy (EM) and a negative group A rotavirus enzyme
      linked immunosorbent assay (ELISA) result. An antigen-detection ELISA was
      developed with hyperimmune antibodies raised to human group C rotavirus
      recombinant VP6 (Bristol strain) expressed in insect cells. The assay was used to
      screen fecal samples to determine the prevalence of group C rotavirus infection.
      Samples positive by ELISA were confirmed by EM, polyacrylamide gel
      electrophoresis of double-stranded RNA, or detection of the VP6 gene by reverse
      transcription-PCR. Retrospective analysis indicated a 1 to 2% detection rate of
      positivity among samples from patients with acute diarrhea.

PMID- 9774562
TI  - Sequencing of Escherichia coli O111 O-antigen gene cluster and identification of
      O111-specific genes.
AB  - Shiga toxin (Stx)-producing Escherichia coli strains of serogroup O111 are the
      most frequently isolated non-O157 strains causing outbreaks of gastroenteritis
      with hemolytic-uremic syndrome. The O111 O-antigen gene cluster had been cloned
      and about half of it has been sequenced; we have now sequenced the remainder of
      the gene cluster, which is 12.5 kb in length and which comprises 11 genes. On the
      basis of sequence similarity, we have identified all the O-antigen genes
      expected, including five sugar biosynthetic pathway genes, three transferase
      genes, the O-unit flippase gene, and the O-antigen polymerase gene. By PCR
      testing with E. coli strains representing all 166 O-antigen forms, some randomly
      selected gram-negative bacteria, and Salmonella enterica serovar Adelaide, we
      showed that four O-antigen genes are highly specific to O111. This work provides
      the basis for a sensitive test for the rapid detection of E. coli O111. This is
      important both for decisions related to patient care, because early treatment may
      reduce the risk of life-threatening complications, and for the detection of
      sources of contamination.

PMID- 9774563
TI  - Inducible beta-lactam resistance in Aeromonas hydrophila: therapeutic challenge
      for antimicrobial therapy.
AB  - Despite the abundant amount of knowledge about inducible chromosomally mediated
      beta-lactamases among Aeromonas species, extended-spectrum beta-lactam-resistant
      A. hydrophila strains selected in clinical practice were rarely reported. In the
      present study, two strains of A. hydrophila, A136 and A139, with markedly
      different susceptibilities to extended-spectrum cephalosporins were isolated from
      blood and the tip segment of an arterial catheter of a burn patient. Another
      strain (A136m) was selected in vitro by culturing A136 in a subinhibitory
      concentration of cefotaxime, the beta-lactam agent administered for the treatment
      of Aeromonas bacteremia in this patient. Typing studies by arbitrarily primed PCR
      and pulsed-field gel electrophoresis indicated a clonal relationship among
      strains A136, A136m, and A139. These strains were identified to be of DNA
      hybridization group 1. Wild-type strain A136 was resistant only to ampicillin and
      cephamycins, but A136m and A139 were highly resistant to the expanded- and broad
      spectrum cephalosporins. The presence of increased beta-lactamase activity in
      A139 suggests that A139 is a derepressed mutant which overexpresses beta
      lactamases. These results call attention to the use of beta-lactam agents for the
      treatment of invasive Aeromonas infections.

PMID- 9774564
TI  - Identification of Legionella species by random amplified polymorphic DNA
      profiles.
AB  - Random amplified polymorphic DNA (RAPD) was used for the identification of
      Legionella species. Primer SK2 (5'-CGGCGGCGGCGG-3') and standardized RAPD
      conditions gave the technique a reproducibility of 93 to 100%, depending on the
      species tested. Species-specific patterns corresponding to the 42 Legionella
      species were consequently defined by this method; the patterns were dependent on
      the recognition of a core of common bands for each species. This specificity was
      demonstrated by testing 65 type strains and 265 environmental and clinical
      isolates. No serogroup-specific profiles were obtained. A number of unidentified
      Legionella isolates potentially corresponding to new species were clustered in
      four groups. RAPD analysis appears to be a rapid and reproducible technique for
      identification of Legionella isolates to the species level without further
      restriction or hybridization.

PMID- 9774565
TI  - Characterization of a type-common human recombinant monoclonal antibody to herpes
      simplex virus with high therapeutic potential.
AB  - We report the characterization of a type-common human recombinant monoclonal
      antibody previously isolated by antigen selection from a phage-displayed
      combinatorial antibody library established from a herpes simplex virus (HSV)
      seropositive individual. Competition with well-characterized murine monoclonal
      antibodies and immunodetection of gD truncations revealed that this antibody
      recognizes the group Ib antigenic site of glycoprotein D, a highly conserved and
      protective type-common determinant. To our knowledge, this is the first human
      group Ib monoclonal antibody ever described. The antibody also displayed first
      order neutralization kinetics and a high neutralization rate constant, was
      capable of completely inhibiting syncytium formation by a fusogenic strain of HSV
      type 1, and efficiently neutralized low-passage clinical isolates of both HSV
      serotypes. Taken together with our earlier observations of the in vivo antiviral
      activities of this human recombinant antibody in animal models of HSV infection,
      the present results support the high therapeutic potential of this antibody.

PMID- 9774566
TI  - Diagnosis of Trichomonas vaginalis infection by PCR using vaginal swab samples.
AB  - Trichomonas vaginalis infection is the most prevalent nonviral sexually
      transmitted disease (STD) in the world. A PCR test using vaginal swab samples for
      the detection of T. vaginalis was developed to add T. vaginalis infection to the
      growing list of STDs that can be detected by DNA amplification techniques. A
      primer set, BTUB 9/2, was designed to target a well-conserved region in the beta
      tubulin genes of T. vaginalis. All strains (15 of 15) of T. vaginalis tested were
      successfully detected by PCR giving a single predicted product of 112 bp in gel
      electrophoresis. No such targeted product was amplified with DNA from Trichomonas
      tenax, Trichomonas gallinae, Chlamydia trachomatis, Neisseria gonorrhoeae,
      Giardia lamblia, Chilomastix sulcatus, Dientamoeba fragilis, and Entamoeba
      histolytica. An optimal analytical sensitivity of one T. vaginalis organism per
      PCR was achieved. Culture, performed with the Inpouch TV culture system, was
      examined daily with a light microscope to identify T. vaginalis. Twenty-three of
      350 (6.6%) vaginal swab samples from women attending an army medical clinic were
      culture positive for T. vaginalis. Of these culture positive specimens, PCR
      detected 22 of 23 (96%) with primer set BTUB 9/2, and wet preparation detected
      only 12 of 23 (52%). Seventeen specimens were BTUB 9/2-PCR positive and culture
      negative. Ten of these discordant specimens were determined to be as true
      positive by PCR using primer sets TVA 5-1/6 and/or AP65 A/B, which target
      different regions in the T. vaginalis genome, and seven were determined to be
      false positive. The sensitivity of BTUB 9/2-PCR was 97% and the specificity was
      98%. The sensitivities of culture and wet preparation were 70 and 36%,
      respectively. The diagnosis of T. vaginalis infection by PCR is a sensitive and
      specific method that could be incorporated into a joint strategy for the
      screening of multiple STDs by using molecular amplification methods.

PMID- 9774567
TI  - Detection of Ureaplasma urealyticum by PCR and biovar determination by liquid
      hybridization.
AB  - An assay which combines the direct detection of Ureaplasma urealyticum with
      biovar determination was developed and applied to 618 urogenital specimens. U.
      urealyticum was detected by inhibitor-controlled PCR. A 429-bp fragment of the
      urease gene was amplified. The amplicons were labelled with digoxigenin during
      PCR. Biovar determination was performed by liquid hybridization with biotin
      labelled biovar-specific probes, and the hybrids were detected with peroxidase
      conjugated sheep anti-digoxigenin immunoglobulin G Fab fragments. Results of PCR
      and culture for 453 urogenital specimens from women and 105 urethral specimens
      from men could be compared. Among the specimens from women, 63% were PCR positive
      as well as culture positive, 0.9% were positive only by PCR, and 4% were positive
      only by culture. Among the specimens from men, 15% were PCR positive as well as
      culture positive, 1% were positive only by PCR, and 9% were positive only by
      culture. By using culture as the reference method, the PCR had a sensitivity of
      94% and a specificity of 98% when applied to specimens from women and a
      sensitivity of 64% and a specificity of 99% when applied to specimens from men.
      Overall, 80% of the PCR-positive specimens contained biovar 1,13.5% contained
      biovar 2, and 6.5% contained both biovars.

PMID- 9774568
TI  - Identification of Brucella by ribosomal-spacer-region PCR and differentiation of
      Brucella canis from other Brucella spp. pathogenic for humans by carbohydrate
      profiles.
AB  - Molecular and chemical characteristics often provide complementary information in
      the differentiation of closely related organisms. The genus Brucella consists of
      a highly conserved group of organisms. Identification of the four species
      pathogenic in humans (Brucella melitensis, Brucella abortus, Brucella suis, and
      Brucella canis) is problematic for many clinical laboratories that depend
      primarily on serology and phenotypic characteristics to differentiate species.
      PCR amplification of the 16S-23S ribosomal DNA interspace region was evaluated
      for species-specific polymorphism. B. abortus, B. melitensis, B. suis, and B.
      canis produced identical PCR interspace profiles. However, these PCR products
      were unique to brucellae, allowing them to be readily distinguished from other
      gram-negative bacteria (including Bartonella spp. and Agrobacterium spp.).
      Carbohydrate profiles differentiated B. canis from the other three Brucella
      species due to the absence of the rare amino sugar quinovosamine in the three
      other species. PCR of the rRNA interspace region is useful in identification of
      the genus Brucella, while carbohydrate profiling is capable of differentiating B.
      canis from the other Brucella species.

PMID- 9774570
TI  - Performance of the Gen-Probe AMPLIFIED Chlamydia Trachomatis Assay in detecting
      Chlamydia trachomatis in endocervical and urine specimens from women and urethral
      and urine specimens from men attending sexually transmitted disease and family
      planning clinics.
AB  - The Gen-Probe AMPLIFIED Chlamydia Trachomatis Assay (AMP CT) uses transcription
      mediated amplification and hybridization protection assay procedures to
      qualitatively detect Chlamydia trachomatis rRNA in urine, endocervical swab, and
      urethral specimens. The performance of the AMP CT was compared to that of cell
      culture for endocervical swab and urine specimens from women and urethral and
      urine specimens from men. Analysis of specimens with discrepant results was
      performed by a combination of reculture, direct fluorescent-antibody (DFA)
      staining of specimen sediment, and amplification which targeted a different
      chlamydial rRNA. A total of 800 urine samples were tested by the AMP CT (607 from
      women and 193 from men), and 7. 1% were positive for C. trachomatis, with a
      sensitivity of 91.2% and a specificity of 99.6% upon discrepant analysis. A total
      of 926 swab specimens were tested by culture and AMP CT (717 endocervical swab
      specimens and 209 urethral swab specimens from men), and 7.7% were positive for
      C. trachomatis, with a sensitivity and specificity of 100% upon discrepant
      analysis. The AMP CT is a sensitive and specific nucleic acid hybridization assay
      for the detection of C. trachomatis in endocervical swab specimens from women,
      urethral swab specimens from men, and urine specimens from men and women.

PMID- 9774569
TI  - Detection and characterization of novel rotavirus strains in the United States.
AB  - We recently established a rotavirus strain surveillance system in the United
      States to monitor the prevalent G serotypes before and after the anticipated
      implementation of a vaccination program against rotavirus and to identify the
      emergence of uncommon strains. In this study, we examined 348 rotavirus strains
      obtained in 1996 to 1997 from children with diarrhea in 10 U.S. cities. Strains
      were characterized for P and G types, subgroups, and electropherotypes by using a
      combination of monoclonal antibody immunoassay, reverse transcription-PCR, and
      hybridization. The four strains most commonly found worldwide comprised 83% of
      the isolates (P[8]G1, 66.4%; P[4]G2, 8.3%; P[8]G3, 6.9%; P[8]G4, 1.4%), but 9.2%
      were unusual strains (P[6]G9, 5.5%; P[8]G9, 1.7%; P[6]G1, 1.4%; and P[4]G1 and
      P[8]G2, 0. 3% each). Strains not typeable for P or G type accounted for 5.5% of
      the total, while 2.3% of the strains had more than one G type (mixed infections).
      All P[6]G9 strains tested had short electropherotypes and subgroup I specificity
      and were detected in 4 of 10 cities, while P[8]G9 strains had long
      electropherotypes and subgroup II VP6 antigens. Both sequence analysis of the VP7
      open reading frame (about 94 to 95% amino acid identity with the VP7 gene of G9
      prototype strain WI61) and binding to a G9-specific monoclonal antibody strongly
      suggest that U.S. G9 strains belong to serotype G9. The high detection rates of
      unusual rotaviruses with G9 (7.2%) or P[6] (6.9%) specificity in multiple U.S.
      cities suggest the emergence of new strains or inadequate diagnosis in the past.
      The epidemiologic importance of these strains remains to be determined.

PMID- 9774571
TI  - Comparison of the MB/BacT system with a revised antibiotic supplement kit to the
      BACTEC 460 system for detection of mycobacteria in clinical specimens.
AB  - The MB/BacT system (MB/BacT) with a revised antibiotic supplement kit was
      compared with the BACTEC 460 system (BACTEC 460) in a test of 488 specimens
      submitted for mycobacterial culture from 302 patients. Twenty-four Mycobacterium
      tuberculosis isolates were detected by the BACTEC 460 versus 23 isolates by the
      MB/BacT. Mean time until detection of M. tuberculosis isolates identified by both
      systems was 11.9 days for the BACTEC 460 versus 13.7 days for the MB/BacT (P =
      0.046). M. avium complex was detected in 12 specimens by the MB/BacT versus 10
      specimens by the BACTEC 460. Only 8 of 14 (57%) M. avium isolates were detected
      by both systems, with a mean time until detection of 10.1 days for the BACTEC 460
      and 14.2 days for the MB/BacT (P = 0.009). The BACTEC 460 and the MB/BacT
      detected M. gordonae in four specimens, but only a single specimen was positive
      by both systems. One M. fortuitum isolate and one of five M. kansasii isolates
      were recovered only by the BACTEC 460. The bacterial overgrowth rate was 7.0% for
      the MB/BacT versus 4.1% for the BACTEC 460. We found the MB/BacT to be comparable
      to the BACTEC 460 for mycobacterial detection. Even though time until detection
      with the MB/BacT was slightly longer (1.8 days longer for M. tuberculosis and 4.1
      days for M. avium [mean values]) and the bacterial overgrowth rate was somewhat
      higher, the decreased labor, the availability of a computerized data management
      system, and the noninvasive, nonradiometric aspects of the MB/BacT offset these
      relative disadvantages and make it an acceptable alternative for use in the
      diagnostic laboratory.

PMID- 9774572
TI  - Prevalence of Porphyromonas gingivalis and periodontal health status.
AB  - Periodontitis is a common, progressive disease that eventually affects the
      majority of the population. The local destruction of periodontitis is believed to
      result from a bacterial infection of the gingival sulcus, and several clinical
      studies have provided evidence to implicate Porphyromonas gingivalis. If P.
      gingivalis is a periodontal pathogen, it would be expected to be present in most
      subjects with disease and rarely detected in subjects with good periodontal
      health. However, in most previous studies, P. gingivalis has not been detected in
      the majority of subjects with disease, and age-matched, periodontally healthy
      controls were not included for comparison. The purpose of the study reported here
      was to compare the prevalence of P. gingivalis in a group with periodontitis to
      that of a group that is periodontally healthy. A comprehensive sampling strategy
      and a sensitive PCR assay were used to maximize the likelihood of detection. The
      target sequence for P. gingivalis-specific amplification was the transcribed
      spacer region within the ribosomal operon. P. gingivalis was detected in only 25%
      (46 of 181) of the healthy subjects but was detected in 79% (103 of 130) of the
      periodontitis group (P < 0.0001). The odds ratio for being infected with P.
      gingivalis was 11.2 times greater in the periodontitis group than in the healthy
      group (95% confidence interval, 6.5 to 19.2). These data implicate P. gingivalis
      in the pathogenesis of periodontitis and suggest that P. gingivalis may not be a
      normal inhabitant of a periodontally healthy dentition.

PMID- 9774573
TI  - Detection of active infection in nonhuman primates with Lyme neuroborreliosis:
      comparison of PCR, culture, and a bioassay.
AB  - Ideally a diagnosis of infection of the central nervous system (CNS) is made by
      culture of the etiologic pathogen, but Borrelia burgdorferi, the causative agent
      of Lyme neuroborreliosis (LNB), is rarely cultured from the cerebrospinal fluid
      (CSF). PCR and measurement of specific antibody in the CSF also have their
      limitations. The role of available assays for LNB has not been studied carefully
      in a comparative investigation. There is a need to assess the reliability of
      assays and to increase the ability to document active infection in the CNS. The
      recent development of the nonhuman primate (NHP) model of LNB allowed us to
      address this need in a faithful model of human LNB. In this study we compared the
      abilities of PCR and culture to detect the presence of spirochetes in the CSF and
      brain tissue of infected NHPs and related these measures of infection to the
      development of anti-B. burgdorferi antibody. We also tested a bioassay, the mouse
      infectivity test (MIT), in this model. Fourteen of 16 CSFs from four NHPs were
      positive by at least one of these techniques. Detection of spirochetes in the CSF
      by PCR, the MIT, and culture was inversely related to the concomitant presence of
      anti-B. burgdorferi antibody intrathecally. The performance of any particular
      test was associated with the strength of the host immune response. In early CNS
      infection, when anti-B. burgdorferi antibody had not yet appeared, or in
      immunocompromised hosts, the MIT compared favorably to culture and PCR for
      infected NHPs; antibody in the CSF was the most useful assay for immunocompetent
      NHPs.

PMID- 9774574
TI  - Comparison of PCR- and hybrid capture-based human papillomavirus detection
      systems using multiple cervical specimen collection strategies.
AB  - This study compared the performances of three human papillomavirus (HPV)
      detection tests with specimens collected by three alternative procedures. The HPV
      tests included the Hybrid Capture Tube test (HCT), the microplate-based Hybrid
      Capture II test (HC II), and the MY09-MY11 L1 consensus primer PCR-based assay.
      Initial cervical specimens were collected from study subjects with a broom
      device, and after Papanicolaou smears were made, residual specimens were placed
      into PreservCyt (PC), a liquid cytology medium. A second specimen was collected
      from each subject and placed into Digene Specimen Transport Medium (STM). The
      device for collection of the second specimen alternated with consecutive subjects
      between a conical cytology brush and a Dacron swab. At the 1.0-pg/ml cutoff, the
      results of the HC II agreed well with those of the PCR. Specifically, when PCR
      data were restricted to the types found by the HC II (HPV types 16, 18, 31, 33,
      35, 39, 45, 51, 52, 56, 58, 59, and 68), there was greater than 90% agreement
      between the HC II and PCR results with both STM and PC. At a lower cutoff (0.2
      pg/ml), HC II-positive results increased further, especially when the test was
      applied to the PC specimens. However, false-positive HC II results were more
      often observed at the 0.2-pg/ml cutoff. HC II yielded the highest HPV positivity
      with specimens placed into PC, followed by specimens collected with a conical
      brush and placed into STM and, last, by those collected with a Dacron swab and
      placed into STM. Our results demonstrate the utility of both the STM and PC
      specimen collection methods and show good agreement between the HC II and PCR.

PMID- 9774575
TI  - Multilocus genotypic analysis of Cryptosporidium parvum isolates from different
      hosts and geographical origins.
AB  - The genetic analysis of oocysts recovered from the stools of humans and animals
      infected with Cryptosporidium parvum has consistently shown the existence of two
      distinct genotypes. One of the genotypes is found exclusively in some human
      infections, whereas the other genotype is found in human as well as in animal
      infections. On the basis of these observations and the results of published
      epidemiological studies with single polymorphic markers, the existence of two
      separate transmission cycles has been postulated, one exclusively anthroponotic
      and the other involving both animals and humans. To test this hypothesis, C.
      parvum isolates of different geographic and host origins were analyzed by using
      unlinked genetic polymorphisms. A total of 28 isolates originating from Europe,
      North and South America, and Australia were examined. Isolates clustered into two
      groups, one comprising both human and animal isolates and the other comprising
      isolates only of human origin. The absence of recombinant genotypes is consistent
      with two reproductively isolated populations within the species C. parvum.

PMID- 9774577
TI  - Serratia ficaria: a misidentified or unidentified rare cause of human infections
      in fig tree culture zones.
AB  - Serratia ficaria, an enterobacterium involved in the fig tree ecosystem, has been
      isolated from human clinical samples in rare instances, and its role as a
      pathogen is unclear. In 7 years, we have isolated S. ficaria from seven patients;
      it was the only pathogen in 4 patients, including a patient with septicemia
      described previously and three patients with gallbladder empyemas described in
      the present report. From March 1995 to July 1997, the incidence of biliary
      infections due to S. ficaria was 0.7%. We discuss the digestive carriage of this
      bacterium and its epidemiology with respect to the fig tree life cycle. Since fig
      trees grow around the Mediterranean as well as in the United States (California,
      Louisiana, Hawaii), S. ficaria should be more frequently isolated. In our
      experience, various strains have been misidentified or unidentified by commercial
      systems. Incorrect identification could be an additional explanation for the
      paucity of reported cases. S. ficaria produces nonpigmented, lactose-negative
      colonies which give off a potatolike odor. This odor is the primary feature of S.
      ficaria and must prompt reexamination of the identifications proposed by
      commercial systems. We tested 42 novel strains using three commercial systems:
      Vitek gram-negative identification (GNI) cards and API 20E and ID 32E strips
      (bioMerieux, Marcy-l'Etoile, France). The percentages of positivity that we have
      obtained were lower than those published previously for the following
      characteristics: lipase, gelatinase, DNase, and rhamnose. The best system for the
      recognition of S. ficaria is ID 32E, which correctly identified 27 of 42 strains.
      The API 20E system gave correct identifications for only two strains. S. ficaria
      was not present in the Vitek GNI card system database.

PMID- 9774576
TI  - Rapid identification of Candida species with species-specific DNA probes.
AB  - Rapid identification of Candida species has become more important because of an
      increase in infections caused by species other than Candida albicans, including
      species innately resistant to azole antifungal drugs. We previously developed a
      PCR assay with an enzyme immunoassay (EIA) format to detect amplicons from the
      five most common Candida species by using universal fungal primers and species
      specific probes directed to the ITS2 region of the gene for rRNA. We designed
      probes to detect seven additional Candida species (C. guilliermondii, C. kefyr,
      C. lambica, C. lusitaniae, C. pelliculosa, C. rugosa, and C. zeylanoides)
      included in the API 20C sugar assimilation panel, five probes for species not
      identified by API 20C (C. haemulonii, C. norvegica, C. norvegensis, C. utilis,
      and C. viswanathii), and a probe for the newly described species C. dubliniensis,
      creating a panel of 18 Candida species probes. The PCR-EIA correctly identified
      multiple strains of each species tested, including five identified as C. albicans
      by the currently available API 20C database but determined to be C. dubliniensis
      by genotypic and nonroutine phenotypic characteristics. Species identification
      time was reduced from a mean of 3.5 days by conventional identification methods
      to 7 h by the PCR-EIA. This method is simple, rapid, and feasible for identifying
      Candida species in clinical laboratories that utilize molecular identification
      techniques and provides a novel method to differentiate the new species, C.
      dubliniensis, from C. albicans.

PMID- 9774578
TI  - Use of the BacT/Alert blood culture system for culture of sterile body fluids
      other than blood.
AB  - Studies have demonstrated that large-volume culture methods for sterile body
      fluids other than blood increase recovery compared to traditional plated-medium
      methods. BacT/Alert is a fully automated blood culture system for detecting
      bacteremia and fungemia. In this study, we compared culture in BacT/Alert
      standard aerobic and anaerobic bottles, BacT/Alert FAN aerobic and FAN anaerobic
      bottles, and culture on routine media for six specimen types, i.e., continuous
      ambulatory peritoneal dialysate (CAPD), peritoneal, amniotic, pericardial,
      synovial, and pleural fluids. Specimen volumes were divided equally among the
      three arms of the study. A total of 1,157 specimens were tested, with 227
      significant isolates recovered from 193 specimens. Recovery by method was as
      follows: standard bottles, 186 of 227 (82%); FAN bottles, 217 of 227 (96%); and
      routine culture, 184 of 227 (81%). The FAN bottles recovered significantly more
      gram-positive cocci (P < 0.001), Staphylococcus aureus (P = 0.003), coagulase
      negative staphylococci (P = 0.008), gram-negative bacilli (P < 0.001),
      Enterobacteriaceae (P = 0.005), and total organisms (P < 0.001) than the routine
      culture. There were no significant differences in recovery between the standard
      bottles and the routine culture. The FAN aerobic bottle recovered significantly
      more gram-positive cocci (P < 0.001), S. aureus isolates (P < 0.001), coagulase
      negative staphyococci (P = 0.003), and total organisms (P < 0.001) than the
      standard aerobic bottle, while the FAN anaerobic bottle recovered significantly
      more gram-positive cocci (P < 0.001), S. aureus isolates (P < 0.001),
      Enterobacteriaceae (P = 0.03), and total organisms (P < 0.001) than the standard
      anaerobic bottle. For specific specimen types, significantly more isolates were
      recovered from the FAN bottles compared to the routine culture for synovial (P <
      0.001) and CAPD (P = 0.004) fluids. Overall, the FAN bottles were superior in
      performance to both the standard bottles and the routine culture for detection of
      microorganisms from the types of sterile body fluids included in this study.

PMID- 9774579
TI  - Characterization of monoclonal antibodies to the 44-kilodalton major outer
      membrane protein of the human granulocytic ehrlichiosis agent.
AB  - The major outer membrane proteins (OMPs) of the human granulocytic ehrlichiosis
      (HGE) agent, with molecular sizes of 44 to 47 kDa, are immunodominant antigens in
      human infection. Monoclonal antibodies (MAbs) to the OMPs were made by immunizing
      BALB/c mice with the purified HGE agent and then by fusing spleen cells with
      myeloma cells. The immunologic specificities of three MAbs (3E65, 5C11, and 5D13)
      were examined with five human HGE agent isolates and one tick isolate. By Western
      blot analysis, all three MAbs recognized the HGE agent but not Ehrlichia
      chaffeensis, Ehrlichia sennetsu, Ehrlichia canis, or their host cells. MAb 3E65
      reacted with a 44-kDa protein in the homologous human isolate but not in the
      remaining five isolates. The two remaining MAbs recognized proteins with
      molecular sizes of 44 to 47 kDa in all six isolates. Western blot results with
      the OMP fraction of the six isolates were consistent with results with the whole
      HGE agent. Immunofluorescent-antibody staining and immunogold labeling with these
      MAbs showed that these antigens were primarily present on the membrane of the HGE
      agent. MAbs 5C11 and 5D13 recognized the recombinant 44-kDa protein by Western
      immunoblot analysis, but MAb 3E65 did not. Passive immunization with MAb 3E65 was
      more effective in protecting mice from HGE agent infection than with MAbs 5C11
      and 5D13. These MAbs would be useful for analyzing the role of the major OMP
      antigens in HGE agent infection and for serodiagnosis.

PMID- 9774580
TI  - Detection of point mutations associated with resistance of Helicobacter pylori to
      clarithromycin by hybridization in liquid phase.
AB  - When the standard procedure for determining antibiotic susceptibility of bacteria
      is used, the results are delayed, especially for bacteria that grow slowly, such
      as Helicobacter pylori. Treatment for this bacterium may involve clarithromycin,
      a compound for which resistance has been associated with point mutations on the
      23S rRNA gene. This resistance is currently found in organisms isolated from 0 to
      15% of patients and jeopardizes the success of the treatment. We have designed a
      test involving amplification and colorimetric hybridization in the liquid phase
      to detect the mutation at the molecular level. First, four reference strains,
      including the wild type and three strains with the mutations A2143C, A2143G, and
      A2144G, were used to optimize the method. Amplification was carried out with
      primers previously published. The amplified products were added to probe-coated
      microtiter wells. A DNA enzyme immunoassay was used to detect the hybrids. The
      optimal conditions of the hybridization were defined for each probe. Nineteen H.
      pylori strains resistant to clarithromycin and 22 susceptible according to
      phenotypic data were submitted to restriction with BsaI and BbsI, and part of the
      23S rRNA gene was sequenced in order to determine the mutation involved for the
      resistant strains. The new assay showed a complete correlation with the reference
      methods, except for one strain. Cross-hybridizations as well as application of
      the reaction to other bacteria did not lead to optical densities higher than the
      cutoff values chosen with the receiving operating characteristic curve. This
      method can be easily standardized and gives a result within a day. Its
      application directly to the biopsy specimens or infected gastric juice is planned
      in the future.

PMID- 9774581
TI  - Extraintestinal salmonellosis in a general hospital (1991 to 1996): relationships
      between Salmonella genomic groups and clinical presentations.
AB  - Episodes of extraintestinal salmonellosis treated at a general hospital (1,522
      beds) over a 6-year period (1991 to 1996) were characterized by the analysis of
      phenotypic and genotypic traits of Salmonella organisms and clinical data from
      medical reports. Extraintestinal salmonellosis accounted for 8% of all
      salmonellosis episodes. Fifty-two medical reports, dealing with 6 cases of
      typhoid fever, 32 cases of bacteremia, and 14 focal infections, were reviewed.
      All cases of typhoid fever except 1, 7 cases of bacteremia, and 5 focal
      infections were not related to any underlying disease or predisposing factors,
      while 25 cases of bacteremia and 9 focal infections were associated with some of
      these risk factors. All typhoid isolates and 65.4% of the nontyphoid isolates
      were susceptible to antimicrobials. Fifty-one nontyphoid strains were analyzed
      and assigned to 21 genomic groups, which were defined by serotype, combined
      ribotype, and combined randomly amplified polymorphic DNA type (each genomic
      group could include organisms differing in some phenotypic traits). The
      relationships between genomic groups and clinical presentations were traced.
      Organisms causing 22 episodes (17 episodes of bacteremia, 2 of pneumonia, 1 of
      peritonitis, 1 of pyelonephritis, and 1 of cystitis) belonged to a prevalent
      Salmonella enterica serotype Enteritidis genomic group, which included organisms
      assigned to four phage types, five biotypes, and four resistance patterns,
      causing infections in patients with and without risk factors. Seven other genomic
      groups, 4 Enteritidis groups (associated with both bacteremia and focal
      infections), 2 Typhimurium groups (one associated with bacteremia and the other
      with focal infections) and 1 Brandenburg group (associated with bacteremia)
      included two or more strains, and the remaining 13 genomic groups consisted of
      only one strain each.

PMID- 9774582
TI  - Genetic heterogeneity of clinical strains of Yersinia enterocolitica traced by
      ribotyping and relationships between ribotypes, serotypes, and biotypes.
AB  - A series of 74 Yersinia enterocolitica clinical strains collected in a Spanish
      region and 10 reference strains, assigned to nine serotypes and five biotypes,
      were analyzed by ribotyping procedures. Riboprobing, performed separately with
      HindIII and BglI and using an rrn operon as the probe, generated 13 and 11
      ribotypes (discrimination index [DI] = 0.56 and 0.55), respectively. PCR
      ribotyping, performed with primers complementary to conserved regions of 16S and
      23S rRNA genes, generated 13 ribotypes (DI = 0. 56). A combination of data from
      the three procedures allowed for further discrimination into 17 combined
      ribotypes (DI = 0.83). The dendrogram obtained by cluster analysis of data from
      riboprobing indicated a high heterogeneity of the ribosomal DNA regions of the
      strains under study (similarities between 10 and 92%), which were grouped into
      three clusters at a similarity level of 0.32. The major cluster included 10
      branches, and 7 of these formed a subcluster (similarity coefficient, >83%)
      represented by strains of serotype O:3 and biotype 2, 3, or 4. The second cluster
      included four branches, represented by strains belonging to seven non-O:3
      serotypes, biotypes 1A and 2, and two of these branches included pyrazinamidase
      positive as well as pyrazinamidase-negative strains. The remaining three
      branches, represented by O:3-biotype 4 strains, formed a third cluster weakly
      related to the others. Data from this study showed that Y. enterocolitica O:3
      organisms assigned to a prevalent and endemic lineage and non-O:3 organisms
      assigned to three other less-frequent lineages are circulating and causing human
      disease in the Spanish region under study.

PMID- 9774583
TI  - Molecular analysis of glycopeptide-resistant Enterococcus faecium isolates
      collected from Michigan hospitals over a 6-year period.
AB  - The purpose of this study was to evaluate the molecular relatedness of clinical
      isolates of glycopeptide-resistant Enterococcus faecium isolates collected from
      hospitals in Michigan. A total of 379 isolates used in this study were all
      vancomycin-resistant E. faecium isolates collected from 28 hospitals and three
      extended-care facilities over a 6-year period from 1991 to 1996. For the 379
      isolates, there were 73 pulsed-field gel electrophoresis (PFGE) strain types.
      Within strain types, there were as many as six restriction fragment differences.
      Most isolates (70%) belonged to six strain types, which were designated M1 (36%),
      M2 (3%), M3 (18%), M4 (6%), M10 (4%), and M11 (3%). PFGE strain M1 was cultured
      from 135 patients in 13 hospitals during the period 1993 to 1996. Strain type M2
      was cultured from 11 patients in two hospitals during the period 1991 to 1992 and
      was not observed after 1992. Strain type M3 was cultured from 70 patients in 10
      hospitals during the period of 1994 to 1996. Both M4 and M10 were cultured from
      23 patients in three hospitals and from 15 patients in two hospitals,
      respectively, during 1995 to 1996. M11 was cultured from 13 patients in four
      hospitals during 1996. A total of 23 of 28 hospitals had evidence of clonal
      dissemination of some isolates. Plasmid content and hybridization analysis done
      on 103 isolates from one hospital and two affiliated extended-care facilities
      indicated that the strains contained from one to eight plasmids. Mating
      experiments indicated transfer of vancomycin resistance from 94 of these isolates
      into plasmid-free E. faecium GE-1 at transfer frequencies of <10(-9) to 10(-4).
      Gentamicin resistance and erythromycin resistance were cotransferred at various
      frequencies. A probe for the vanA gene hybridized to the plasmids of 23 isolates
      and to the chromosomes of 72 isolates. A probe for the vanB gene hybridized to
      the chromosomes of 8 isolates. The results of this study suggest inter- and
      intrahospital dissemination of vancomycin-resistant E. faecium strains over a 6
      year period in southeastern Michigan. The majority of isolates studied belonged
      to the same few PFGE strains, indicating that clonal dissemination was
      responsible for most of the spread of resistance that occurred.

PMID- 9774584
TI  - Antigenemia in patients with paracoccidioidomycosis: detection of the 87
      kilodalton determinant during and after antifungal therapy.
AB  - Serological diagnosis and follow-up of paracoccidioidomycosis (PCM) patients have
      relied mainly on the detection of antibody responses by using techniques such as
      complement fixation (CF) and immunodiffusion. We recently described a novel
      inhibition enzyme-linked immunosorbent assay (inh-ELISA) which proved to be
      useful in the diagnosis of PCM via the detection of an 87-kDa determinant in
      patient sera (B. L. Gomez, J. I. Figueroa, A. J. Hamilton, B. Ortiz, M. A.
      Robledo, R. J. Hay, and A. Restrepo, J. Clin. Microbiol. 35:3278-3283, 1997).
      This test has now been assessed as a means of following up PCM patients. A total
      of 24 PCM patients, classified according to their clinical presentation (6 with
      the acute form of the disease, of whom two had AIDS, 12 with the multifocal form
      of the disease, and 6 with the unifocal form of the disease), were studied. The
      four human immunodeficiency virus-negative patients with acute PCM showed a
      statistically significant decrease in circulating antigen levels after the start
      of antifungal therapy. Antigen levels in this group became negative by our
      criteria (</=2.3 microgram/ml) before week 20 and remained so in three of four of
      these patients. In contrast, the two AIDS patients who also presented with the
      acute form of PCM showed no statistically significant decrease in circulating
      antigen levels even after 68 weeks of therapy. Taken together as a group, the
      patients with the multifocal form showed a statistically significant decrease in
      antigenemia after 28 weeks of therapy. In addition, five of six patients with the
      unifocal form became antigen negative by week 40. Antigen level decrease mirrored
      clinical cure in the majority of patients in all clinical groups; in contrast,
      measurement of anti-PCM antibodies via the CF test showed wide fluctuations in
      titers during the follow-up period. The inh-ELISA for the detection of the 87-kDa
      Paracoccidioides brasiliensis determinant would appear to be a valuable
      additional tool in the follow-up of PCM patients.

PMID- 9774586
TI  - PCR method for detection of adenovirus in urine of healthy and human
      immunodeficiency virus-infected individuals.
AB  - Adenoviruses (AdV) cause diseases that range from localized, self-limited
      illnesses to fatal infections in immunocompromised patients. Culture is assumed
      to be sensitive but requires viable virus and up to 3 weeks for detection, and it
      can be inhibited by bacterial contamination. A new PCR method amplifying a region
      of the hexon gene was developed in order to detect AdV in urine more rapidly and
      with greater sensitivity than obtainable by culture technology. All 18 serotypes
      tested were detected. Quantitatively, with optimized urine processing, AdV PCR
      detected 0.2 PFU/ml (serotype 11) and 10 DNA copies/ml (serotype 2). Serially
      collected urine samples from human immunodeficiency virus (HIV)-infected patients
      with concurrent cytomegalovirus retinitis were divided into three groups: AdV
      culture-positive samples, AdV culture-negative or bacterially contaminated
      samples from patients with a history of AdV culture-positive urines, and AdV
      culture-negative samples from patients without a history of AdV culture
      positivity. Urine samples from healthy adults were also tested by culture and PCR
      to screen for asymptomatic shedding. Amplification was assessed with and without
      prior DNA purification. AdV was detected by PCR in 90% of culture-positive urines
      (100% of unclotted samples, e.g., those culture positive after storage for PCR
      testing), 71% of culture-negative or bacterially contaminated urines from AdV
      infected patients, and 28% from AdV culture-negative patients. Healthy volunteers
      were culture negative for AdV, and 96% were PCR negative. The new AdV PCR method
      is rapid and sensitive and can detect viral DNA in samples for which culturing is
      problematic. The role of AdV replication during HIV infection merits further
      investigation with sensitive tools such as PCR.

PMID- 9774585
TI  - Identification of new verocytotoxin type 2 variant B-subunit genes in human and
      animal Escherichia coli isolates.
AB  - The sequence of a verocytotoxin 2 (VT2) variant gene that was untypeable by the B
      subunit PCR and restriction fragment length polymorphism analysis (PCR-RFLP)
      method described by Tyler et al. (S. D. Tyler, W. M. Johnson, H. Lior, G. Wang,
      and K. R. Rozee, J. Clin. Microbiol. 29:1339-1343, 1991) was determined and
      compared with published sequences. It was highly homologous to two recently
      reported VT2 variant sequences. The PCR-RFLP method described by Tyler et al. was
      extended to include these new sequences. New VT2 variants were identified in 65
      of 359 VT-producing Escherichia coli (VTEC) with newly designed primers (VT2-cm
      and VT2-f) and were characterized as well by restriction analysis of the
      amplification products obtained with another VT2-specific primer pair (VT2-e and
      VT2-f). The VT genes harbored by 64 of these isolates proved to be untypeable by
      Tyler's PCR-RFLP method because no amplification was obtained with the primers
      used with this method (VT2-c and VT2-d). The last isolate harbored the new
      variant gene in addition to VT2vh-a. None of the isolates harboring these new
      toxin genes belonged to serogroups O157, O26, O103, O111, and O145. All 65
      isolates were negative for the eaeA gene and were significantly less frequently
      enterohemolytic or positive for the enterohemorrhagic E. coli (EHEC) virulence
      plasmid than non-O157 VTEC isolates harboring other VT2 genes. They were also
      less frequently isolated from patients with EHEC-associated symptoms. The
      extended PCR-RFLP typing method is a useful tool to identify less-virulent VTEC
      isolates and for VT genotyping in epidemiological studies with non-O157 strains.

PMID- 9774587
TI  - Comparison of genomic methods for differentiating strains of Enterococcus
      faecium: assessment using clinical epidemiologic data.
AB  - Genomic DNA extracted from 45 vancomycin-resistant Enterococcus faecium (VRE)
      isolates was cleaved with HindIII and HaeIII and subjected to agarose gel
      electrophoresis. The ability of this method (restriction endonuclease analysis
      [REA]) to distinguish strains at the subspecies level was compared with results
      previously determined by pulsed-field gel electrophoresis (PFGE). Chart reviews
      were performed to provide a clinical correlation of possible epidemiologic
      relatedness. A likely clinical association was found for 29 patients as part of
      two outbreaks. REA found 21 of 21 isolates were the same type in the first
      outbreak, with PFGE calling 19 strains the same type. In the second outbreak with
      eight patient isolates, HindIII found six were the same type and two were unique
      types. HaeIII found three strains were the same type, two strains were a separate
      type, and three more strains were unique types, while PFGE found three were the
      same type and five were unique types. No single "ideal" method can be used
      without clinical epidemiologic investigation, but any of these techniques is
      helpful in providing focus to infection control practitioners assessing possible
      outbreaks of nosocomial infection.

PMID- 9774589
TI  - Development of a new cytomegalovirus (CMV) immunoglobulin M (IgM) immunoblot for
      detection of CMV-specific IgM.
AB  - We developed a new cytomegalovirus (CMV) immunoglobulin M (IgM) immunoblot to
      detect CMV-specific IgM in human sera. The new test contains four viral proteins
      (vp150, vp82, vp65, and vp28) purified from viral particles and four recombinant
      proteins (rp150, rp130, rp52, and rp38) purified from Escherichia coli. These
      antigens were individually loaded onto nitrocellulose strips, and the strips were
      then used to detect CMV-specific IgM by using a mu-specific conjugate. The new
      assay was evaluated in parallel with one or two IgM enzyme-linked immunosorbent
      assays (ELISAs) to test 592 serum samples from different groups of latently or
      acutely infected individuals. The sensitivity of the new assay with respect to
      the consensus of two ELISAs was 100%, the specificity was 98.6%, the positive
      predictive value was 96.9%, and the negative predictive value was 100%. We also
      evaluated the new test by testing sera from pregnant women and transplant
      recipients with a known clinical history. Our results suggest that the new test
      combines high sensitivity with high specificity, characteristics that are
      mutually exclusive with the other commercially available tests. Furthermore, a
      statistically significant correlation was observed between the number of IgM
      reactive bands and the elevated risk of transmission from CMV-infected pregnant
      women to their offspring.

PMID- 9774588
TI  - Characterization of La Crosse virus RNA in autopsied central nervous system
      tissues.
AB  - A reverse transcription-PCR (RT-PCR) technique was used to detect La Crosse (LAC)
      virus RNA in the central nervous system (CNS) tissues of two patients who died of
      LAC encephalitis in 1960 and 1978. Viral RNA was readily detected by RT-PCR
      although the tissues had been stored frozen for up to 37 years. LAC virus was
      detected in the cerebral cortex but not in other CNS tissues. RT-PCR allowed
      detection of replicative forms of the virus, indicating that the virus was
      actively replicating in the specific CNS tissues. The small (S) RNA segments of
      the viruses from the CNS samples were demonstrated to be genetically similar by
      single-strand conformation polymorphism analyses. These S RNA segments were then
      sequenced; only two base changes were demonstrated between the 1960 and the 1978
      samples, suggesting that LAC virus is genetically stable in areas of endemicity.
      The RT-PCR analyses of analyte directly from CNS tissues allows study of the
      virus without passage in cell culture.

PMID- 9774590
TI  - Two-color hybridization assay for simultaneous detection of Bordetella
      bronchiseptica and toxigenic Pasteurella multocida from swine.
AB  - Bordetella bronchiseptica and toxigenic Pasteurella multocida are the etiologic
      agents of swine atrophic rhinitis. Methods currently used for their
      identification are time-consuming and suffer from a lack of sensitivity. We
      describe a colony lift-hybridization assay for detection of B. bronchiseptica and
      toxigenic P. multocida that can be performed with a single colony lift derived
      from a primary isolation plate without the need for pure subcultures of suspect
      bacteria. Membranes are hybridized simultaneously to probes derived from the B.
      bronchiseptica alcA gene and the P. multocida toxA gene. A multicolor development
      procedure permits sequential detection of bound probes. The assay was tested with
      84 primary isolation plates generated from nasal swabs from swine with clinical
      signs of atrophic rhinitis. Comparison of the results from the colony lift
      hybridization assay with those from conventional testing, based on a combination
      of colony morphology, biochemical reactions, mouse lethality, and enzyme-linked
      immunosorbent assay, indicated that the colony lift assay has superior
      sensitivity and comparable specificity. This technique has wide application for
      diagnostic and experimental studies.

PMID- 9774591
TI  - Endocarditis and aortal embolization caused by Aspergillus terreus in a patient
      with acute lymphoblastic leukemia in remission: diagnosis by peripheral-blood
      culture.
AB  - Disseminated infection with Aspergillus terreus is a rare disease that affects
      only the immunocompromised host. We report a case of systemic infection with A.
      terreus resulting in endocarditis, aortic embolization, and splenic infarction in
      a patient with acute lymphoblastic leukemia. Diagnosis through peripheral blood
      culture, lack of pulmonary involvement, and onset of disease during complete
      remission from leukemia constitute uncommon features of this case.

PMID- 9774592
TI  - Genetic heterogeneity of Borrelia burgdorferi sensu lato in Ixodes ricinus ticks
      collected in Belgium.
AB  - Borrelia burgdorferi sensu lato (s.l.), the etiological agent of Lyme disease, is
      transmitted by the bite of Ixodes ricinus. Four hundred eighty-nine ticks,
      collected in four locations of a region of southern Belgium where Lyme disease is
      endemic, were examined for the presence of the spirochete. In a PCR test with
      primers that recognize a chromosomal gene of all strains, 23% of the ticks were
      found to be infected. The species B. burgdorferi s.l. comprises at least three
      pathogenic genomospecies, B. burgdorferi sensu stricto (s.s.), Borrelia garinii,
      and Borrelia afzelii, which could be distinguished in PCR tests with species
      specific primers that correspond to distinct plasmid sequences. B. garinii was
      most prevalent (53% of infected ticks), followed by B. burgdorferi s.s. (38%) and
      B. afzelii (9%). Of the infected ticks, 40% were infected with a single species,
      40% were infected with two species, and 5% were infected with all three species.
      For 15% of the ticks, the infecting species could not be identified. No
      difference in rates of prevalence was observed among the four locations, which
      had similar ground covers, even though they belonged to distinct biogeographic
      regions. A greater heterogeneity of spirochetal DNA in ticks than in cultured
      reference DNA was suggested by a comparison of the results of PCRs with two
      different sets of species-specific primer sequences.

PMID- 9774593
TI  - Detection and typing of Borrelia burgdorferi sensu lato in Ixodes ricinus ticks
      attached to human skin by PCR.
AB  - Live Ixodes ricinus ticks attached to humans residing in Germany were examined
      for borreliae by dark-field microscopy and PCR. Borrelia species were identified
      by 16S rRNA sequence analysis, which showed the presence of several species, some
      not yet defined, and a high prevalence of multiply infected ticks.

PMID- 9774594
TI  - Development and evaluation of an Epstein-Barr virus (EBV) immunoglobulin M enzyme
      linked immunosorbent assay based on the 18-kilodalton matrix protein for
      diagnosis of primary EBV infection.
AB  - A new immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA) based on
      the recombinant Epstein-Barr virus (EBV) matrix protein was developed. Compared
      to indirect immunofluorescence for the detection of IgM antibody to the EBV
      capsid antigen on clinical specimens, the sensitivity and specificity of the new
      IgM ELISA were 96 and 96%, respectively.

PMID- 9774595
TI  - Distribution of hepatitis B virus genotypes in two different pediatric
      populations from Argentina.
AB  - Differences in pathogenesis and the probability of becoming a chronic carrier
      depend on the age at which hepatitis B virus (HBV) infection is acquired, ranging
      from 82% in infants less than 6 months of age to 15 to 30% in older children. HBV
      genotypes from 22 pediatric patients from two areas that differ in prevalence
      have been determined. Phylogenetic analysis shows a clear difference between the
      genotype distribution in Buenos Aires, a low-prevalence area, and that found in
      Gualeguay, Entre Rios, a high-prevalence area. While the analysis allocated the
      sequences in the Buenos Aires group to genotypes A (36%), D (9%), and F (55%),
      the Gualeguay group presented exclusively genotype A isolates with very low
      nucleotide divergence, which suggests a strong founder viral population. The high
      prevalence of genotype F in the Buenos Aires group and its high intragroup
      heterogeneity agree with the American origin of this genotype.

PMID- 9774596
TI  - Comparison of systems for identification and differentiation of species within
      the genus Yersinia.
AB  - Of four tested identification systems (API 20E, API Rapid 32 IDE, Micronaut E,
      and the PCR-based Yersinia enterocolitica Amplification Set), API 20E is still
      the system of choice for identifying pathogenic Yersinia isolates. It provides
      the highest sensitivity both at the genus and at the species level and has the
      best cost-effectiveness correlation.

PMID- 9774597
TI  - Comparison of costs of strategies for measuring levels of human immunodeficiency
      virus type 1 RNA in plasma by using Amplicor and Ultra Direct assays.
AB  - The costs of four algorithms for monitoring plasma human immunodeficiency virus
      type 1 RNA were compared. For patients with strong virologic responses, the use
      of Ultra Direct exclusively was the cheapest strategy. For patients with weak
      virologic responses, small savings could be obtained by using Amplicor and
      retesting only samples with values below 500 copies/ml with Ultra Direct.

PMID- 9774598
TI  - Evaluation of the Nuclisens HIV-1 QT assay for quantitation of human
      immunodeficiency virus type 1 RNA levels in plasma.
AB  - Nuclisens HIV-1 QT is a new version of the NASBA HIV-1 QT assay for quantitation
      of human immunodeficiency virus type 1 (HIV-1) RNA in plasma. The specificity of
      this assay was 100% in one laboratory and 99%-with nonrepeatability of the
      initial false positive-in another. The test was linear between 2.0 and 6.0 log
      RNA copies per ml. According to the input HIV-1 RNA concentration, accuracy
      varied from -0.11 to +0.10 log RNA copy per ml and precision varied from 0.66 to
      0.14 log RNA copy per ml. Reproducibility decreased when the HIV-1 RNA level was
      near the lower limit of quantitation of the test. HIV-1 RNA could be quantitated
      by Nuclisens HIV-1 QT in 36% (laboratory 1) and 24% (laboratory 2) of clinical
      samples with HIV-1 RNA levels lower than the lower limit of quantitation by NASBA
      HIV-1 QT. Nuclisens HIV-1 QT was not suitable for measurement of RNA from clade G
      and group O HIV-1 strains.

PMID- 9774599
TI  - Application of multiplex PCR for detection of non-O157 verocytotoxin-producing
      Escherichia coli in bloody stools: identification of serogroups O26 and O111.
AB  - Primers were designed to amplify sequences of verocytotoxin genes and eaeA genes
      of Escherichia coli O26:H11, O111:H8, and O157:H7 in a multiplex PCR assay. This
      assay successfully detected E. coli O26:H11 in bloody stool specimens in which
      other enteric pathogens were not detected by culture-based methods. Rapid assays
      to detect non-O157:H7 verocytotoxin-producing E. coli is important to improve
      methods for the etiologic diagnosis of hemorrhagic colitis.

PMID- 9774600
TI  - Sequence variation in the small-subunit rRNA gene of Plasmodium malariae and
      prevalence of isolates with the variant sequence in Sichuan, China.
AB  - By two PCR-based diagnostic methods, Plasmodium malariae infections have been
      rediscovered at two foci in the Sichuan province of China, a region where no
      cases of P. malariae have been officially reported for the last 2 decades. In
      addition, a variant form of P. malariae which has a deletion of 19 bp and seven
      substitutions of base pairs in the target sequence of the small-subunit (SSU)
      rRNA gene was detected with high frequency. Alignment analysis of Plasmodium sp.
      SSU rRNA gene sequences revealed that the 5' region of the variant sequence is
      identical to that of P. vivax or P. knowlesi and its 3' region is identical to
      that of P. malariae. The same sequence variations were also found in P. malariae
      isolates collected along the Thai-Myanmar border, suggesting a wide distribution
      of this variant form from southern China to Southeast Asia.

PMID- 9774601
TI  - Evaluation of a commercial PCR kit for diagnosis of cytomegalovirus infection of
      the central nervous system.
AB  - We evaluated the AMPLICOR cytomegalovirus (CMV) PCR kit for the diagnosis of
      neurologic CMV infections on 43 positive and 112 negative archived cerebrospinal
      fluid specimens originally tested by an in-house PCR method. The AMPLICOR kit
      showed sensitivity and specificity of 95 and 100%, respectively, versus the home
      grown assay, indicating its utility in this clinical setting.

PMID- 9774602
TI  - Evaluation of strategies for molecular fingerprinting for use in the routine work
      of a Mycobacterium reference unit.
AB  - We have investigated the role of two rapid PCR-based typing methods, IS6110-based
      PCR and spacer-oligonucleotide typing, within a national tuberculosis reference
      service. The validity of clusters with IS6110 restriction fragment length
      polymorphism fingerprints with less than 6 bands was also investigated in the
      context of referred isolates.

PMID- 9774603
TI  - First isolation of Trichophyton fischeri in the United States.
AB  - A 49-year-old male with Pneumocystis carinii pneumonia was seen at Bellevue
      Hospital in New York, N.Y. Sputum samples yielded cultures of Candida lusitaniae,
      Mycobacterium avium, and a filamentous fungus, Trichophyton fischeri. T. fischeri
      is a nonpathogenic fungus which resembles the dermatophyte Trichophyton rubrum.
      This is the first record of the species from U.S. sources. This case exemplifies
      the ecological differences between T. fischeri and T. rubrum and illustrates how
      correct identification of the former species can minimize diagnostic confusion.
      The two species are distinguished from each other by the type of growth on
      Casamino Acids-erythritol-albumin agar and by micromorphological differences.

PMID- 9774604
TI  - Comparison of the QUANTIPLEX HIV-1 RNA 2.0 assay with the AMPLICOR HIV-1 MONITOR
      1.0 assay for quantitation of levels of human immunodeficiency virus type 1 RNA
      in plasma of patients receiving stavudine-didanosine combination therapy.
AB  - We compared the QUANTIPLEX HIV-1 RNA 2.0 assay with the AMPLICOR HIV-1 MONITOR
      1.0 assay for quantitation of human immunodeficiency virus type 1 (HIV-1) RNA in
      plasma in the Stadi trail, which evaluated a stavudine plus didanosine
      combination therapy in 52 patients. HIV-1 RNA baseline values measured with
      AMPLICOR HIV-1 MONITOR 1.0 were significantly higher than those measured with
      QUANTIPLEX HIV-1 RNA 2.0, and decreases in HIV-1 RNA levels from baseline were
      also found to be significantly higher when measured with the AMPLICOR HIV-1
      MONITOR 1.0 assay. The frequency of HIV-1 RNA levels below the lower limit of
      quantitation was significantly higher with QUANTIPLEX HIV-1 RNA 2.0 than with
      AMPLICOR HIV-1 MONITOR 1.0. Reanalysis of these results by an ultrasensitive
      procedure of AMPLICOR HIV-1 MONITOR 1.0 or by a modified version of the test that
      included additional primers adapted for non-B HIV-1 clades yielded greater
      differences between the QUANTIPLEX HIV-1 RNA 2.0 assay and the AMPLICOR HIV-1
      MONITOR 1.0 assay. Our results indicate that a valid comparison of the
      virological efficacies obtained with different antiretroviral drug regimens
      requires the use of the same viral load quantitation procedure; further
      standardization between the different HIV-1 RNA quantitation kits is therefore
      needed.

PMID- 9774605
TI  - Efficacy of API 20C and ID 32C systems for identification of common and rare
      clinical yeast isolates.
AB  - The abilities of the API 20C and ID 32C yeast identification systems to identify
      123 common and 120 rare clinical yeast isolates were compared. API 20C
      facilitated correct identification of 97% common and 88% rare isolates while ID
      32C facilitated correct identification of 92% common and 85% rare isolates.

PMID- 9774606
TI  - Determination of 16S rRNA sequences of enterococci and application to species
      identification of nonmotile Enterococcus gallinarum isolates.
AB  - The 16S rRNA sequences of enterococcal species E. faecium, E. faecalis, E.
      gallinarum, E. casseliflavus/flavescens, E. dispar, E. pseudoavium, E. sulfureus,
      E. malodoratus, E. raffinosus, E. cecorum, E. hirae, E. saccharolyticus, E.
      seriolicida, E. mundtii, E. avium, E. durans, E. columbae, and E. solitarius are
      presented herein. These data were utilized to confirm the species identification
      of two nonmotile E. gallinarum isolates which had been previously phenotypically
      identified as E. faecium. The implications of this finding are discussed.

PMID- 9774607
TI  - Enhancement of the AMPLICOR enterovirus PCR test with a coprecipitant.
AB  - The incorporation of a commercially available coprecipitant into the AMPLICOR
      enterovirus PCR test specimen preparation enhanced the sensitivity and
      reproducibility of this assay. Fifty-five previously tested archived
      cerebrospinal fluids (CSF) specimens were tested in a blind study in duplicate
      with and without Pellet Paint coprecipitant (Novagen, Inc., Madison, Wis.). Of
      these specimens, 26 had previously been determined to be positive and 29 had
      previously been determined to be negative. All previously positive CSF specimens
      were positive when Pellet Paint was used and only 18 were positive without Pellet
      Paint. No previously negative specimens were positive on repeat testing with or
      without Pellet Paint. The background signal was not affected by the addition of
      Pellet Paint. These data support the utility of a coprecipitant in minimizing
      false-negative results.

PMID- 9774608
TI  - Evaluation of a leukocyte stabilization reagent for use in the cytomegalovirus
      pp65 antigenemia assay.
AB  - New erythrocyte lysis and leukocyte stabilization reagents (Streck Laboratories,
      Inc.) were tested in the cytomegalovirus pp65 antigenemia assay, to determine if
      whole-blood processing time could be delayed to 24 h postdraw. The combination of
      these reagents gave results comparable to those for patient samples processed
      immediately after blood draw.

PMID- 9774609
TI  - Molecular characterization of Bacillus strains involved in outbreaks of anthrax
      in France in 1997.
AB  - Outbreaks of anthrax zoonose occurred in two regions of France in 1997. Ninety
      four animals died, and there were three nonfatal cases in humans. The diagnosis
      of anthrax was rapidly confirmed by bacteriological and molecular biological
      methods. The strains of Bacillus anthracis in animal and soil samples were
      identified by a multiplex PCR assay. They all belonged to the variable-number
      tandem repeat (VNTR) group (VNTR)3. A penicillin-resistant strain was detected.
      Nonvirulent bacilli related to B. anthracis, of all VNTR types, were also found
      in the soil.

PMID- 9774610
TI  - In vitro activities of ampicillin-sulbactam and amoxicillin-clavulanic acid
      against Acinetobacter baumannii.
AB  - In vitro susceptibility patterns of newer beta-lactamase-inhibiting antibiotics
      ampicillin-sulbactam (A/S) and amoxicillin-clavulanic acid (A/C) for 100
      consecutive isolates of Acinetobacter baumannii obtained from various clinical
      samples were studied. The A/C MIC for 86% of the strains was more than 16/8
      microgram/ml, whereas there was an A/S MIC of more than 16/8 microgram/ml for
      only 38% of the strains. This showed that A/S has significantly superior in vitro
      activity compared to A/C against A. baumannii, although, theoretically, both
      should have similar activities. The therapeutic superiority of A/S over A/C needs
      to be studied, or else the breakpoints for these agents in in vitro tests need to
      be redefined.

PMID- 9774611
TI  - Correlation between presence of viable bacteria and presence of endotoxin in
      middle-ear effusions.
AB  - The presence of endotoxin (detected by the Limulus amebocyte lysate assay) was
      compared to the presence of viable Haemophilus influenzae and Moraxella
      catarrhalis (detected by PCR) in 106 middle-ear effusions from pediatric patients
      with chronic otitis media. Endotoxin was found in 81 of the 106 specimens. Of
      these 81 specimens, 66 (81.5%) also tested positive for one or both of the gram
      negative bacteria H. influenzae and M. catarrhalis. The data suggest that viable
      gram-negative bacteria, detectable by PCR but often undetectable by culture, may
      be the source of endotoxin in middle-ear effusions.

PMID- 9774612
TI  - Effect of oxygen on growth of Mycobacterium ulcerans in the BACTEC system.
AB  - The effect of low oxygen concentration on the growth of 15 strains of
      Mycobacterium ulcerans was evaluated in the BACTEC system. Reduced oxygen tension
      enhanced the growth of M. ulcerans, suggesting that this organism has a
      preference for microaerobic environments. Application of this observation may
      improve rates of isolation of M. ulcerans in primary culture from clinical
      samples and promote isolation of the bacterium from environmental sources.

PMID- 9774613
TI  - Pretreatment with restriction enzyme or bovine serum albumin for effective PCR
      amplification of Epstein-Barr virus DNA in DNA extracted from paraffin-embedded
      gastric carcinoma tissue.
AB  - An association between Epstein-Barr virus (EBV) and gastric carcinoma has been
      studied through the EBV genome present in the carcinoma cells. Recently, we found
      that EBV DNA in paraffin-embedded gastric carcinoma tissue was detected
      effectively by PCR after pretreatment of the extracted DNA with a restriction
      enzyme, BamHI or EcoRI. Here, we show that the PCR amplification was also
      enhanced by pretreatment of the DNA with other restriction enzymes or with bovine
      serum albumin and several other proteins. Treatment with these proteins may
      remove a PCR inhibitor(s) in the DNA samples extracted from the paraffin blocks.

PMID- 9774614
TI  - Prevalence of specific antibodies to Chlamydia pneumoniae in Korea.
AB  - To clarify the endemic status of Chlamydia pneumoniae in Korea, the incidence of
      antibodies in 564 serum samples from healthy individuals, patients with
      respiratory infection, and cord blood specimens was evaluated. We conclude that
      C. pneumoniae infection is highly endemic in Korea and that this infection is
      associated with acute respiratory diseases.

PMID- 9774615
TI  - Fluconazole disk diffusion susceptibility testing of Candida species.
AB  - We describe a simple procedure for detecting fluconazole-resistant yeasts by a
      disk diffusion method. Forty clinical Candida sp. isolates were tested on RPMI
      glucose agar with either 25- or 50-microgram fluconazole disks. With 25-microgram
      disks, zones of inhibition of >/=20 mm at 24 h accurately identified 29 of 29
      isolates for which MICs were </=8 microgram/ml, and with 50-microgram disks,
      zones of >/=27 mm identified 28 of 29 such isolates. All 11 isolates for which
      MICs were >8 microgram/ml were identified by using either disk. Disk diffusion
      may be a useful screening method for clinical microbiology laboratories.

PMID- 9774616
TI  - Comparison of four serological tests to determine the CagA or VacA status of
      Helicobacter pylori strains.
AB  - We compared four tests for antibodies to CagA or VacA, HelicoBlot 2. 0, RIDA Blot
      Helicobacter, CHIRON RIBA H. pylori SIA, and an enzyme-linked immunosorbent assay
      using recombinant CagA. Immunoblot assays were accurate for determining
      Helicobacter pylori status but poor for determining CagA or VacA status
      (accuracy, 66 to 80% for CagA status and 34 to 67% for VacA status). None can be
      recommended for determining CagA or VacA status.

PMID- 9774617
TI  - Helicobacter pylori cagA status and s and m alleles of vacA in isolates from
      individuals with a variety of H. pylori-associated gastric diseases.
AB  - The cagA gene was detected in 100% of 16 Helicobacter pylori isolates from
      patients with gastric carcinoma versus 78% of 18 isolates from patients with
      duodenal ulcers (P = 0.344) and only 64% of 22 isolates from patients with
      gastritis only (P = 0.005) in Brazil. Also, there was a significant association
      between isolation of cagA+ s1-type vacA H. pylori in cases of stomach cancer and
      ulcers as opposed to cases of gastritis only (P = 0.004), but this was not true
      in Houston (P = 0.238), where 94% of all isolates were cagA+.

PMID- 9774618
TI  - Development of a nested PCR for detection of Cryptococcus neoformans in
      cerebrospinal fluid.
AB  - We report the development of a nested-PCR-based assay for the detection of
      Cryptococcus neoformans in cerebrospinal fluid. The specificity and sensitivity
      of the test were assessed. The technique was then applied to 40 cerebrospinal
      fluid samples. We obtained positive reactions for all 21 clinical samples from
      patients who had been previously diagnosed as having cryptococcal meningitis by
      conventional techniques and negative reactions for all 19 negative controls.
      Nested PCR is here compared with other diagnostic methods currently used in
      patients' follow-up exams during anticryptococcal therapy.

PMID- 9774619
TI  - Comparison of two rapid whole-blood tests for Helicobacter pylori infection in
      Chinese patients.
AB  - Consecutive Chinese patients undergoing endoscopy for dyspepsia were tested for
      Helicobacter pylori infection by two rapid whole-blood tests: FlexPack HP (Abbott
      Laboratories) and Helisal One-Step (Cortecs Diagnostics). Biopsy-based tests
      (rapid urease test and histology) and the [13C]urea breath test were used as the
      "gold standard." One hundred sixty-one consecutive patients were studied, and 88
      (54.7%) were confirmed to have H. pylori infection. The sensitivities,
      specificities, and positive and negative predictive values were 81.8%, 83.6% (P =
      0.008), 85.7% (P = 0.04), and 79.2% for FlexPack HP and 84.1%, 63.0% (P = 0.008),
      73.3% (P = 0.047), and 76.7% for Helisal One-Step, respectively.

PMID- 9774620
TI  - Specific regulation of StAR expression in the rat adrenal zona glomerulosa. An in
      situ hybridization study.
AB  - Steroid acute regulatory protein (StAR) plays an essential role in
      steroidogenesis because it is responsible for the transfer of cholesterol from
      cellular stores to the inner mitochondrial membrane. We investigated the
      distribution and regulation of StAR expression in association with aldosterone
      production in the rat adrenal gland in vivo. Using nonradioactive in situ
      hybridization, we demonstrate that the outermost five to seven parenchymal cell
      layers express the StAR gene only weakly and inhomogeneously. The strongest
      expression is found in the zona fasciculata and zona reticularis. In addition,
      some cells in the adrenal medulla also stained positively. To differentiate
      between functionally active glomerulosa and inactive intermediate cells, we
      compared the expression pattern of StAR with that of aldosterone synthase. The
      expression of the latter is localized to two or three cell layers only, located
      immediately below the capsule. However, the cells of the intermedia are capable
      of expressing both genes prominently, as shown after stimulation with bilateral
      nephrectomy for 2 days. All zones of the adrenal cortex by then expressed StAR
      gene to the same extent. This was accompanied by a 50-fold elevated plasma
      aldosterone concentration. Our data demonstrate that the width of the aldosterone
      producing zone can increase within a short period of time by recruiting
      hormonally inactive cells to steroidogenesis.

PMID- 9774621
TI  - Choline acetyltransferase (ChAT) immunoreactivity in paraffin sections of normal
      and diseased intestines.
AB  - There is increasing interest in localizing nerves in the intestine, especially
      specific populations of nerves. At present, the usual histochemical marker for
      cholinergic nerves in tissue sections is acetylcholinesterase activity. However,
      such techniques are applicable only to frozen sections and have uncertain
      specificity. Choline acetyltransferase (ChAT) is also present in cholinergic
      nerves, and we therefore aimed to establish a paraffin section immunocytochemical
      technique using an anti-ChAT antibody. Monoclonal anti-choline acetyltransferase
      (1.B3.9B3) and a biotin-streptavidin detection system were used to study the
      distribution of ChAT immunoreactivity (ChAT IR) in paraffin-embedded normal and
      diseased gastrointestinal tracts from both rats and humans. Optimal staining was
      seen after 6-24 hr of fixation in neutral buffered formalin and overnight
      incubation in 1 microgram/ml of 1.B3.9B3, with a similar distribution to that
      seen in frozen sections. In the rat diaphragm (used as a positive control), axons
      and motor endplates were ChAT IR. Proportions of ganglion cells and nerve fibers
      in the intramural plexi of both human and rat gastrointestinal tracts were also
      ChAT IR, as well as extrinsic nerve bundles in aganglionic segments of
      Hirschsprung's disease. Mucosal cholinergic nerves, however, were not visualized.
      In addition, non-neuronal cells such as endothelium, epithelium, and inflammatory
      cells were ChAT IR. We were able to localize ChAT to nerves in formalin-fixed,
      paraffin-embedded sections. The presence of ChAT IR in non-neuronal cells
      indicates that this method should be used in conjunction with other antibodies.
      Nevertheless, it proves to be a useful technique for studying cholinergic
      neuronal distinction in normal tissues and pathological disorders.

PMID- 9774622
TI  - Immunoelectronmicroscopic analysis of the ligand-induced internalization of the
      somatostatin receptor subtype 2 in cultured human glioma cells.
AB  - We analyzed the internalization of the receptor subtype 2 (sst2) for the
      neuropeptide somatostatin in glioma cells at the ultrastructural level using an
      antibody against an extracellular amino acid sequence. Intact cells derived from
      solid human gliomas or those of the human glioma cell line U343 were receptor
      labeled (a) by classical gold immunocytochemistry using a 15-nm gold-labeled
      second antibody, (b) directly with the sst2 antibody adsorbed to 5-nm colloidal
      gold, and (c) with the physiological ligand somatostatin conjugated to 5-nm
      colloidal gold. The receptor was predominantly internalized via uncoated vesicles
      budding from the cell membrane but only rarely via coated pits, which has been
      mostly reported for G-protein-coupled, seven transmembrane-domain receptors. In
      the presence of ligand and sst2 antibody vesicles, tubule-like structures, and
      multivesicular bodies were labeled in superficial and in perinuclear portions of
      the cells within the first 30 min. Lysosomal labeling was observed after 30 min
      and especially after an hour of internalization time. This internalization route
      is also used to study the directly labeled sst2 antibody or the labeled ligand.
      However, the late endosomal compartment appears to be reached more rapidly in
      these latter experiments.

PMID- 9774623
TI  - Immunohistochemical analysis of the distribution of the human ATPase (hASNA-I) in
      normal tissues and its overexpression in breast adenomas and carcinomas.
AB  - Human ATPase (hASNA-I) is a novel human gene recently cloned on the basis of
      homology to the arsA gene of bacteria. Its protein product is an ATPase that is
      free in the cytoplasm and bound in the perinuclear area and nucleolus in human
      cells. We prepared the hASNA-I-specific 5G8 monoclonal antibody and used it to
      investigate the expression of hASNA-I in normal human tissues and breast cancers.
      hASNA-I was detected immunohistochemically only in the epithelial cells of the
      liver, kidney, and stomach wall, in the adrenal medulla, in the islet cells of
      the pancreas, in the red pulp of the spleen, and in cardiac and skeletal muscle.
      No staining was observed in the uterus, testis, lung, thyroid, cerebellum, and
      large intestine. Although no staining was also observed in normal breast tissue,
      all four cases of breast fibroadenomas and all 15 cases of either primary or
      metastatic breast carcinoma demonstrated increased staining. No embryological or
      functional common denominator is readily apparent. However, the increased
      expression in malignant breast cells is of particular interest with respect to
      the use of this antibody for screening of cytological specimens.

PMID- 9774624
TI  - Sensitive mRNA detection by fluorescence in situ hybridization using horseradish
      peroxidase-labeled oligodeoxynucleotides and tyramide signal amplification.
AB  - With the ongoing progress in human genome projects, many genes are discovered
      whose function and/or expression pattern are not known. Most of these genes are
      expressed in relatively low abundance compared to housekeeping genes such as
      elongation factor-1alpha and beta-actin. Gene expression is studied by Northern
      blot assays or by semiquantitative PCR methods. Another method is the
      visualization of transcripts in tissue or cell cultures by fluorescence in situ
      hybridization (FISH). However, for low-abundance RNA detection, this method is
      hampered by its limited detection sensitivity and by the interference of
      background signals with specific hybridization signals. Background signals are
      introduced by nonspecific hybridization of probe sequences or nonspecific binding
      of antibodies used for visualization. To eliminate background signals derived
      from both sources and to benefit from the peroxidase-driven tyramide signal
      amplification (TSA), we directly conjugated horseradish peroxidase (HRP) to
      oligodeoxynucleotides (ODNs) and used these probes to study in the bladder cancer
      cell line 5637 the expression of various cytokine genes which, according to
      Northern hybridization and reverse transcriptase-polymerase chain reaction (RT
      PCR) assays, are expressed at levels up to 10,000-fold less than abundantly
      expressed housekeeping genes. The results show that reduction of probe complexity
      and the limited use of immunocytochemical detection layers strongly reduces noise
      signals derived from nonspecific binding of nucleic acid probe and antibodies.
      The use of the HRP-ODNs in combination with TSA allowed detection of low
      abundance cytokine mRNAs by FISH.

PMID- 9774625
TI  - Pre-embedding staining for GAD67 versus postembedding staining for GABA as
      markers for central GABAergic terminals.
AB  - Pre-embedding immunocytochemistry for the active form of glutamate decarboxylase
      (GAD67) and postembedding staining for gamma-aminobutyric acid (GABA) were
      compared as markers for central GABAergic terminals in the phrenic motor nucleus,
      in which phrenic motor neurons had been retrogradely labeled with cholera toxin B
      horseradish peroxidase. Nerve terminals with or without GAD67 immunoreactivity
      were identified in one ultrathin section. GABA was localized with immunogold in
      an adjacent section after etching and bleaching. GABA labeling density was
      assessed over 519 GAD67-positive and GAD67-negative nerve terminals in the
      phrenic motor nucleus. Frequency histograms showed that statistically higher
      densities of gold particles occurred over most GAD67-positive terminals. However,
      some GAD67-negative terminals also showed high densities of gold particles, and
      some GAD67-positive terminals showed low densities. Preabsorption of the anti
      GABA antibody with a GABA-protein conjugate, but not with other amino acid
      protein conjugates, significantly reduced gold labeling over both GAD67-positive
      and GAD67-negative terminals. These results show that the presence of GAD67
      immunoreactivity correlates strongly with high densities of immunogold labeling
      for GABA in nerve terminals in the phrenic motor nucleus. Preabsorption controls
      indicate that authentic GABA was localized in the postembedding labeling
      procedure. Only a small proportion of intensely GABA-immunoreactive terminals
      lack GAD67, suggesting that both GAD67 and GABA are reliable markers of GABAergic
      nerve terminals.

PMID- 9774626
TI  - Localization of nitric oxide synthases and nitric oxide production in the rat
      mammary gland.
AB  - We investigated nitric oxide (NO) production and the presence of nitric oxide
      synthase (NOS) in the mammary gland by use of an organ culture system of rat
      mammary glands. Mammary glands were excised from the inguinal parts of female
      Wistar-MS rats primed by implantation with pellets of 17beta-estradiol and
      progesterone and were diced into approximately 3-mm cubes. Three of these cubes
      were cultured with 2 ml of 10% FCS/DMEM plus carboxy-PTIO (an NO scavenger, 100
      microM) in the presence or absence of LPS (0.5 microgram/ml) for 2 days. The
      amount of NO produced spontaneously by the cultured mammary glands was relatively
      minute at the end of the 2-day culture period, and the NO production was
      significantly enhanced by the presence of LPS. This enhancement of NO production
      was completely eliminated by addition of hydrocortisone (3 microM), an inhibitor
      of inducible NOS (iNOS), to the incubation medium. Immunoblot analyses with
      specific antisera against NOS isoforms such as iNOS, endothelial NOS (eNOS), and
      brain NOS (bNOS) showed immunoreactive bands of iNOS (122 +/- 2 kD) and eNOS (152
      +/- 3 kD) in extracts prepared from the mammary glands in the culture without
      LPS. The immunoreactive band of iNOS was highly intense after the treatment of
      mammary glands with LPS, whereas the corresponding eNOS immunoreactive band was
      faded. The immunohistochemical study of anti-iNOS antiserum on frozen sections of
      the cultured mammary glands showed that an immunoreactive substance with the
      antiserum was localized to the basal layer (composed of myoepithelial cells of
      alveoli and lactiferous ducts) of the mammary epithelia and to the endothelium of
      blood vessels that penetrated into the interstitium of the mammary glands.
      Histochemical staining for NADPH-diaphorase activity, which is identical to NOS,
      showed localization similar to that of iNOS in the mammary glands. Similar
      observations were noted in the immunohistochemistry of eNOS. In contrast, the
      immunoreactive signal with the bNOS antiserum was barely detected in the
      epithelial parts of alveoli and lactiferous ducts of the mammary glands. These
      observations demonstrate that three isoforms of NOS are present not only in the
      endothelium of blood vessels but also in the parenchymal cells (the glandular
      epithelium) of the rat mammary gland, such as epithelial cells and myoepithelial
      cells, and suggest that NO may have functional roles in the physiology of the
      mammary glands.

PMID- 9774627
TI  - In situ staining for poly(ADP-ribose) polymerase activity using an NAD analogue.
AB  - Poly(ADP-ribose) polymerase (PARP) is a highly abundant nuclear enzyme which
      metabolizes NAD, in response to DNA strand breakage, to produce chains of
      poly(ADP-ribose) attached to nuclear proteins. PARP activation has been
      implicated in ischemia/reperfusion injury, but its biological significance is not
      fully understood. We have modified an existing in situ method for detection of
      PARP activity by using an NAD analogue in which adenine is modified by an
      "etheno" (vinyl) bridge. Etheno-NAD serves as a PARP substrate in an initial
      enzymatic reaction; a specific antibody to ethenoadenosine is then used in an
      immunohistochemical reaction to detect the production of modified poly(ADP
      ribose). The method produces strong and specific labeling of nuclei in which PARP
      has been activated, i.e., those in which DNA strand breaks have been produced,
      and the results can be analyzed by microscopy, flow cytometry, or colorimetry.
      The method is applicable to cultured cells in several formats and to frozen
      tissue sections. The particular characteristics of the new method may assist in
      future in situ studies of PARP activation.

PMID- 9774628
TI  - Expression of heat shock proteins in mouse skin during wound healing.
AB  - Wound healing conditions generate a stressful environment for the cells involved
      in the regeneration process and are therefore postulated to influence the
      expression of heat shock proteins (Hsps). We have examined the expression of four
      Hsps (Hsp27, Hsp60, Hsp70 and Hsp90) and a keratin (keratin 6) by
      immunohistochemistry during cutaneous wound repair from Day 1 to Day 21 after
      wounding in the mouse. Hsps were constitutively expressed in normal mouse
      epidermis and their patterns of expression were modified during the healing
      process. The changes were not directly linked to the time course of the healing
      process but rather were dependent on the location of cells in the regenerating
      epidermis. In the thickened epidermis, Hsp60 was induced in basal and low
      suprabasal cells, Hsp70 showed a reduced expression, and Hsp90 and Hsp27
      preserved a suprabasal pattern with an induction in basal and low suprabasal
      cells. All Hsps had a uniform pattern of expression in the migrating epithelial
      tongue. These observations suggest that the expression of Hsps in the
      neoepidermis is related to the proliferation, the migration, and the
      differentiation states of keratinocytes within the wound.

PMID- 9774629
TI  - Deimination of 70-kD nuclear protein during epidermal apoptotic events in vitro.
AB  - Peptidylarginine deiminase (PAD) is the enzyme responsible for converting protein
      bound arginine residues to citrulline. It has recently been shown that a number
      of epidermal proteins, including filaggrin, trichohyalin, and keratins, are
      deiminated by the action of PAD, suggesting a possible role for protein
      deimination during the final stages of epidermal differentiation. We report here
      a novel PAD substrate found during the course of identifying deiminated proteins
      in cultured rat epidermal keratinocytes. We found that a 70-kD protein localized
      to the periphery of the nucleus was preferentially deiminated after ionomycin
      treatment in the presence of 2 mM calcium and was associated with apoptotic
      events in these cells. Furthermore, we discovered that the deimination of nuclear
      protein could be induced by transfection of a PAD cDNA into rat epidermal
      keratinocytes. These data suggest that PAD may act on the 70-kD nuclear protein
      to induce disassembly of the nuclear lamina and promote apoptosis during terminal
      epidermal differentiation.

PMID- 9774630
TI  - Lectin-gold localization of fucose residues in human gastric mucosa.
AB  - The oligosaccharides of the mucous gastric glycoproteins are involved in the
      protection of the gastric mucosa and are altered in different diseases.
      Therefore, it is important to know their composition in health, to better
      determine the alterations induced by the disease. Moreover, analysis of the
      molecular composition of the fundic gland cells has been previously used to
      obtain new insights into the origin of the different cell types. The aim of the
      present study was the localization in the subcellular structures of the fucose
      residues of the oligosaccharides in human fundic glands. For this, lectin
      cytochemical methods were used at the light and electron microscopic levels. They
      were combined with enzymatic and chemical treatments to characterize the nature
      of the oligosaccharide chains containing the fucose residues. The presence of
      this carbohydrate belonging to N- or O-linked oligosaccharides has been
      demonstrated in the secretory granules of the surface, gastric pit, mucous neck,
      and transitional cells of the fundic mucosa, and in the intracellular canaliculi
      and tubulovesicular system of the parietal cells. These fucose residues were
      added in the trans-Golgi regions to the elongating chains. Additional fucose
      linked to the innermmost N-acetylglucosamine of the N-linked oligosaccharides was
      found in the chief cells, being incorporated in the cis-Golgi. The findings in
      the transitional cells corroborate the origin of the chief cells from the mucous
      neck cells.

PMID- 9774631
TI  - Immunoelectron microscopic study for polyamines.
AB  - The polyamines (PAs) are ubiquitous polycationic metabolites in eukaryotic and
      prokaryotic cells and are believed to be intimately involved in the regulation of
      DNA, RNA, and protein biosynthesis, the exact function of which remains unclear,
      mainly because of a lack of knowledge of PA subcellular localization. In this
      study, using immunoelectron microscopy, we have demonstrated that PAs are
      predominantly located on free and attached ribosomes of the rough endoplasmic
      reticulum in the neurons of the lateral reticular nucleus of rat medulla
      oblongata. The nuclei, axons, and nerve endings were devoid of PA. This suggests
      that PAs are one of the components of biologically active ribosomes, being
      closely involved in the translation processes of protein biosynthesis.

PMID- 9774632
TI  - Identification of Merkel cells by an antibody to villin.
AB  - Merkel cells represent a population of epithelial cells in the skin and oral
      mucosa. Although Merkel cells are reliably distinguishable from other epithelial
      cells at the ultrastructural level, these cells are usually not discernible by
      standard light microscopy and need special techniques for their identification.
      Villin is an actin-crosslinking protein that is associated with the actin
      filament cores of brush border microvilli. In this study we show that an antibody
      against villin is an excellent marker of Merkel cells and their microvilli even
      at the light microscopic level. The surrounding keratinocytes and subepithelial
      connective tissue cells do not show any significant affinity for the antibody
      against villin. Confocal laser micrographs reconstructed from serial images 0.5
      microm thick of Merkel cells that were immunostained with villin clearly reveal
      the three-dimensional morphology of Merkel cells and their microvilli. The
      presence of villin in Merkel cell microvilli lends support to the idea that these
      cells might have a mechanoreceptor function.

PMID- 9774633
TI  - Expression of 1,25-dihydroxy vitamin D3 receptor in breast carcinoma.
AB  - We investigated immunohistochemically the expression of 1,25 dihydroxy vitamin D3
      receptors (VDRs) in normal human breast tissue and in breast carcinomas. For the
      first time, a VDR immunoreactivity score (VDR-IRS) in breast tissue is presented.
      Mean VDR-IRS in breast carcinomas was 7.28 compared to 1.55 in normal breast
      tissue. Comparing staining patterns for VDR and Ki-67, no visual correlation was
      found, indicating that VDR upregulation in breast carcinomas is not exclusively
      controlled by the proliferative activity of these tumor cells. Our study adds to
      the body of evidence that breast tissue may be a sensitive target organ for
      therapeutically applied new vitamin D analogues that exert few calcemic side
      effects.

PMID- 9774634
TI  - Position-dependent methylation and transcriptional silencing of transgenes in
      inverted T-DNA repeats: implications for posttranscriptional silencing of
      homologous host genes in plants.
AB  - Posttranscriptional silencing of chalcone synthase (Chs) genes in petunia
      transformants occurs by introducing T-DNAs that contain a promoter-driven or
      promoterless Chs transgene. With the constructs we used, silencing occurs only by
      T-DNA loci which are composed of two or more T-DNA copies that are arranged as
      inverted repeats (IRs). Since we are interested in the mechanism by which these
      IR loci induce silencing, we have analyzed different IR loci and nonsilencing
      single-copy (S) T-DNA loci with respect to the expression and methylation of the
      transgenes residing in these loci. We show that in an IR locus, the transgenes
      located proximal to the IR center are much more highly methylated than are the
      distal genes. A strong silencing locus composed of three inverted T-DNAs bearing
      promoterless Chs transgenes was methylated across the entire locus. The host Chs
      genes in untransformed plants were moderately methylated, and no change in
      methylation was detected when the genes were silenced. Run-on transcription
      assays showed that promoter-driven transgenes located proximal to the center of a
      particular IR are transcriptionally more repressed than are the distal genes of
      the same IR locus. Transcription of the promoterless Chs transgenes could not be
      detected. In the primary transformant, some of the IR loci were detected together
      with an unlinked S locus. We observed that the methylation and expression
      characteristics of the transgenes of these S loci were comparable to those of the
      partner IR loci, suggesting that there has been cross talk between the two types
      of loci. Despite the similar features, S loci are unable to induce silencing,
      indicating that the palindromic arrangement of the Chs transgenes in the IR loci
      is critical for silencing. Since transcriptionally silenced transgenes in IRs can
      trigger posttranscriptional silencing of the host genes, our data are most
      consistent with a model of silencing in which the transgenes physically interact
      with the homologous host gene(s). The interaction may alter epigenetic features
      other than methylation, thereby impairing the regular production of mRNA.

PMID- 9774635
TI  - Two independent internal ribosome entry sites are involved in translation
      initiation of vascular endothelial growth factor mRNA.
AB  - The mRNA of vascular endothelial growth factor (VEGF), the major angiogenic
      growth factor, contains an unusually long (1,038 nucleotides) and structured 5'
      untranslated region (UTR). According to the classical translation initiation
      model of ribosome scanning, such a 5' UTR is expected to be a strong translation
      inhibitor. In vitro and bicistronic strategies were used to show that the VEGF
      mRNA translation was cap independent and occurred by an internal ribosome entry
      process. For the first time, we demonstrate that two independent internal
      ribosome entry sites (IRESs) are present in this 5' UTR. IRES A is located within
      the 300 nucleotides upstream from the AUG start codon. RNA secondary structure
      prediction and site-directed mutagenesis allowed the identification of a 49
      nucleotide structural domain (D4) essential to IRES A activity. UV cross-linking
      experiments revealed that IRES A activity was correlated with binding of a 100
      kDa protein to the D4 domain. IRES B is located in the first half of the 5' UTR.
      An element between nucleotides 379 and 483 is required for its activity.
      Immunoprecipitation experiments demonstrated that a main IRES B-bound protein was
      the polypyrimidine tract binding protein (PTB), a well-known regulator of
      picornavirus IRESs. However, we showed that binding of the PTB on IRES B does not
      seem to be correlated with its activity. Evidence is provided of an original
      cumulative effect of two IRESs, probably controlled by different factors, to
      promote an efficient initiation of translation at the same AUG codon.

PMID- 9774636
TI  - Sp1-mediated transcription of the Werner helicase gene is modulated by Rb and
      p53.
AB  - The regulation of Werner's syndrome gene (WRN) expression was studied by
      characterizing the cis-regulatory elements in the promoter region and the trans
      activating factors that bind to them. First, we defined the transcription
      initiation sites and the sequence of the 5' upstream region (2.8 kb) of WRN that
      contains a number of cis-regulatory elements, including 7 Sp1, 9 retinoblastoma
      control element (RCE), and 14 AP2 motifs. A region consisting of nucleotides -67
      to +160 was identified as the principal promoter of WRN by reporter gene assays
      in HeLa cells, using a series of WRN promoter-luciferase reporter (WRN-Luc)
      plasmids that contained the 5'-truncated or mutated WRN upstream regions. In
      particular, two Sp1 elements proximal to the transcription initiation site are
      indispensable for WRN promoter activity and bind specifically to Sp1 proteins.
      The RCE enhances WRN promoter activity. Coexpression of the WRN-Luc plasmids with
      various dosages of plasmids expressing Rb or p53 in Saos2 cells lacking active Rb
      and p53 proteins showed that the introduced Rb upregulates WRN promoter activity
      a maximum of 2. 5-fold, while p53 downregulates it a maximum of 7-fold, both dose
      dependently. Consistently, the overexpressed Rb and p53 proteins also affected
      the endogenous WRN mRNA levels in Saos2 cells, resulting in an increase with Rb
      and a decrease with p53. These findings suggest that WRN expression, like that of
      other housekeeping genes, is directed mainly by the Sp1 transcriptional control
      system but is also further modulated by transcription factors, including Rb and
      p53, that are implicated in the cell cycle, cell senescence, and genomic
      instability.

PMID- 9774637
TI  - Definition of the transcriptional activation domains of three human HOX proteins
      depends on the DNA-binding context.
AB  - Hox proteins control developmental patterns and cell differentiation in
      vertebrates by acting as positive or negative regulators of still unidentified
      downstream target genes. The homeodomain and other small accessory sequences
      encode the DNA-protein and protein-protein interaction functions which ultimately
      dictate target recognition and functional specificity in vivo. The effector
      domains responsible for either positive or negative interactions with the cell
      transcriptional machinery are unknown for most Hox proteins, largely due to a
      lack of physiological targets on which to carry out functional analysis. We
      report the identification of the transcriptional activation domains of three
      human Hox proteins, HOXB1, HOXB3, and HOXD9, which interact in vivo with the
      autoregulatory and cross-regulatory enhancers of the murine Hoxb-1 and human
      HOXD9 genes. Activation domains have been defined both in a homologous context,
      i.e., within a HOX protein binding as a monomer or as a HOX-PBX heterodimer to
      the specific target, and in a heterologous context, after translocation to the
      yeast Gal4 DNA-binding domain. Transfection analysis indicates that activation
      domains can be identified in different regions of the three HOX proteins
      depending on the context in which they interact with the DNA target. These
      results suggest that Hox proteins may be multifunctional transcriptional
      regulators, interacting with different cofactors and/or components of the
      transcriptional machinery depending on the structure of their target regulatory
      elements.

PMID- 9774638
TI  - MFR, a putative receptor mediating the fusion of macrophages.
AB  - We had previously identified a macrophage surface protein whose expression is
      highly induced, transient, and specific, as it is restricted to actively fusing
      macrophages in vitro and in vivo. This protein is recognized by monoclonal
      antibodies that block macrophage fusion. We have now purified this protein and
      cloned its corresponding cDNA. This protein belongs to the superfamily of
      immunoglobulins and is similar to immune antigen receptors such as the T-cell
      receptor, B-cell receptor, and viral receptors such as CD4. We have therefore
      named this protein macrophage fusion receptor (MFR). We show that the
      extracellular domain of MFR prevents fusion of macrophages in vitro and therefore
      propose that MFR belongs to the fusion machinery of macrophages. MFR is identical
      to SHPS-1 and BIT and is a homologue of P84, SIRPalpha, and MyD-1, all of which
      have been recently cloned and implicated in cell signaling and cell-cell
      interaction events.

PMID- 9774639
TI  - Ectopic expression of cdc2/cdc28 kinase subunit Homo sapiens 1 uncouples cyclin B
      metabolism from the mitotic spindle cell cycle checkpoint.
AB  - Primary human fibroblasts arrest growth in response to the inhibition of mitosis
      by mitotic spindle-depolymerizing drugs. We show that the mechanism of mitotic
      arrest is transient and implicates a decrease in the expression of cdc2/cdc28
      kinase subunit Homo sapiens 1 (CKsHs1) and a delay in the metabolism of cyclin B.
      Primary human fibroblasts infected with a retroviral vector that drives the
      expression of a mutant p53 protein failed to downregulate CKsHs1 expression,
      degraded cyclin B despite the absence of chromosomal segregation, and underwent
      DNA endoreduplication. In addition, ectopic expression of CKsHs1 interfered with
      the control of cyclin B metabolism by the mitotic spindle cell cycle checkpoint
      and resulted in a higher tendency to undergo DNA endoreduplication. These results
      demonstrate that an altered regulation of CKsHs1 and cyclin B in cells that carry
      mutant p53 undermines the mitotic spindle cell cycle checkpoint and facilitates
      the development of aneuploidy. These data may contribute to the understanding of
      the origin of heteroploidy in mutant p53 cells.

PMID- 9774640
TI  - Interference between proteins Hap46 and Hop/p60, which bind to different domains
      of the molecular chaperone hsp70/hsc70.
AB  - Several structurally divergent proteins associate with molecular chaperones of
      the 70-kDa heat shock protein (hsp70) family and modulate their activities. We
      investigated the cofactors Hap46 and Hop/p60 and the effects of their binding to
      mammalian hsp70 and the cognate form hsc70. Hap46 associates with the amino
      terminal ATP binding domain and stimulates ATP binding two- to threefold but
      inhibits binding of misfolded protein substrate to hsc70 and reactivation of
      thermally denatured luciferase in an hsc70-dependent refolding system. By
      contrast, Hop/p60 interacts with a portion of the carboxy-terminal domain of
      hsp70s, which is distinct from that involved in the binding of misfolded
      proteins. Thus, Hop/p60 and substrate proteins can form ternary complexes with
      hsc70. Hop/p60 exerts no effect on ATP and substrate binding but nevertheless
      interferes with protein refolding. Even though there is no direct interaction
      between these accessory proteins, Hap46 inhibits the binding of Hop/p60 to hsc70
      but Hop/p60 does not inhibit the binding of Hap46 to hsc70. As judged from
      respective deletions, the amino-terminal portions of Hap46 and Hop/p60 are
      involved in this interference. These data suggest steric hindrance between Hap46
      and Hop/p60 during interaction with distantly located binding sites on hsp70s.
      Thus, not only do the major domains of hsp70 chaperones communicate with each
      other, but cofactors interacting with these domains affect each other as well.

PMID- 9774641
TI  - Synergistic regulation of Schwann cell proliferation by heregulin and forskolin.
AB  - A peptide corresponding to the epidermal growth factor homology domain of beta
      heregulin stimulated autophosphorylation of the heregulin receptors erbB2 and
      erbB3 in Schwann cells and activation of the mitogen-activated protein (MAP)
      kinases ERK1 and ERK2. Heregulin-dependent activation of PAK65, a component of
      the stress-activated signaling pathway, ribosomal S6 kinase, and a cyclic AMP
      (cAMP) response element binding protein (CREB) kinase, identified as p95(RSK2),
      was also observed. Receptor phosphorylation and activation of these kinases in
      response to heregulin occurred in the absence of forskolin stimulation and were
      not augmented in cells treated with forskolin, a direct activator of adenylyl
      cyclase. Schwann cell proliferation in response to heregulin was observed only
      when the cells were also exposed to an agent that elevates cAMP levels. In the
      absence of heregulin, elevation of cAMP levels failed to stimulate Schwann cell
      proliferation. Forskolin significantly enhanced heregulin-stimulated expression
      of cyclin D and phosphorylation of the retinoblastoma gene product. In cells
      treated with both heregulin and forskolin there was a sustained accumulation of
      phospho-CREB, which was not observed in cells treated with either agent alone.
      Heregulin and forskolin synergistically activated transcription of a cyclin D
      promoter construct. These results demonstrate that heregulin-stimulated
      activation of MAP kinase is not sufficient to induce maximal Schwann cell
      proliferation. Expression of critical cell cycle regulatory proteins and cell
      division require activation of both heregulin and cAMP-dependent processes.

PMID- 9774642
TI  - Evidence that immunoglobulin VH-DJ recombination does not require germ line
      transcription of the recombining variable gene segment.
AB  - The importance of V(D)J recombination for generating diversity in the immune
      system is well established, but the mechanisms which regulate V(D)J recombination
      are still poorly understood. Although transcription of unrearranged (germ line)
      immunoglobulin and T-cell receptor gene segments often precedes V(D)J
      recombination and has been implicated in its control, the actual role of germ
      line transcripts in V(D)J recombination is not known. We used a sensitive reverse
      transcription-PCR assay to study immunoglobulin VH germ line transcripts in proB
      lines from RAG-deficient mice. All 10 VH families analyzed were germ line
      transcribed, and germ line transcription was found in all of the cell lines
      examined, indicating that active chromatin was present in the VH region. However,
      not all VH families were germ line transcribed in every cell line, and there was
      a surprising lack of uniformity in the number and family distribution of germ
      line VH transcripts in individual lines. When V(D)J recombination was activated
      by restoration of RAG activity, recombinational activity of endogenous VH genes
      for which germ line transcription was observed could be compared with those of
      genes for which it was not observed. This analysis revealed multiple examples of
      endogenous VH gene segments which were rearranged in cells where their germ line
      transcription was not detectable prior to RAG expression. Thus, our data provide
      strong support for the idea that V-(D)J recombination does not require germ line
      transcription of the recombining variable gene segment.

PMID- 9774643
TI  - Formation of a functional hepatitis B virus replication initiation complex
      involves a major structural alteration in the RNA template.
AB  - The DNA genome of a hepatitis B virus is generated by reverse transcription of
      the RNA pregenome. Replication initiation does not involve a nucleic acid primer;
      instead, the hepadnavirus P protein binds to the structured RNA encapsidation
      signal epsilon, from which it copies a short DNA primer that becomes covalently
      linked to the enzyme. Using in vitro-translated duck hepatitis B virus (DHBV) P
      protein, we probed the secondary structure of the protein-bound DHBV epsilon RNA
      (Depsilon) and observed a marked conformational change compared to free Depsilon
      RNA. Several initiation-competent mutant RNAs with a different free-state
      structure were similarly altered, whereas a binding-competent but initiation
      deficient variant was not, indicating the importance of the rearrangement for
      replication initiation and suggesting a mechanistic coupling to encapsidation.

PMID- 9774644
TI  - Snf1 protein kinase regulates phosphorylation of the Mig1 repressor in
      Saccharomyces cerevisiae.
AB  - In glucose-grown cells, the Mig1 DNA-binding protein recruits the Ssn6-Tup1
      corepressor to glucose-repressed promoters in the yeast Saccharomyces cerevisiae.
      Previous work showed that Mig1 is differentially phosphorylated in response to
      glucose. Here we examine the role of Mig1 in regulating repression and the role
      of the Snf1 protein kinase in regulating Mig1 function. Immunoblot analysis of
      Mig1 protein from a snf1 mutant showed that Snf1 is required for the
      phosphorylation of Mig1; moreover, hxk2 and reg1 mutations, which relieve glucose
      inhibition of Snf1, correspondingly affect phosphorylation of Mig1. We show that
      Snf1 and Mig1 interact in the two-hybrid system and also coimmunoprecipitate from
      cell extracts, indicating that the two proteins interact in vivo. In immune
      complex assays of Snf1, coprecipitating Mig1 is phosphorylated in a Snf1
      dependent reaction. Mutation of four putative Snf1 recognition sites in Mig1
      eliminated most of the differential phosphorylation of Mig1 in response to
      glucose in vivo and improved the two-hybrid interaction with Snf1. These studies,
      together with previous genetic findings, indicate that the Snf1 protein kinase
      regulates phosphorylation of Mig1 in response to glucose.

PMID- 9774645
TI  - The immunoglobulin heavy chain locus control region increases histone acetylation
      along linked c-myc genes.
AB  - In chromosome translocations characteristic of Burkitt lymphomas (BL) and murine
      plasmacytomas, c-myc genes become juxtaposed to immunoglobulin heavy-chain (IgH)
      sequences, resulting in aberrant c-myc transcription. Translocated c-myc alleles
      that retain the first exon exhibit increased transcription from the normally
      minor c-myc promoter, P1, and increased transcriptional elongation through
      inherent pause sites proximal to the major c-myc promoter, P2. We recently
      demonstrated that a cassette derived from four DNase I-hypersensitive sites
      (HS1234) in the 3'Calpha region of the IgH locus functions as an enhancer-locus
      control region (LCR) and directs a similar pattern of deregulated expression of
      linked c-myc genes in BL and plasmacytoma cell lines. Here, we report that the
      HS1234 enhancer-LCR mediates a widespread increase in histone acetylation along
      linked c-myc genes in Raji BL cells. Significantly, the increase in acetylation
      was not restricted to nucleosomes within the promoter region but also was
      apparent upstream and downstream of the transcription start sites as well as
      along vector sequences. Histone hyperacetylation of control c-myc genes, which
      was induced by the deacetylase inhibitor trichostatin A, mimics the effect of the
      HS1234 enhancer on expression from the c-myc P2 promoter, but not that from the
      P1 promoter. These results suggest that the HS1234 enhancer stimulates
      transcription of c-myc by a combination of mechanisms. Whereas HS1234 activates
      expression from the P2 promoter through a mechanism that includes increased
      histone acetylation, a general increase in histone acetylation is not sufficient
      to explain the HS1234-mediated activation of transcription from P1.

PMID- 9774646
TI  - Persistent interactions of core histone tails with nucleosomal DNA following
      acetylation and transcription factor binding.
AB  - In this study, we examined the effect of acetylation of the NH2 tails of core
      histones on their binding to nucleosomal DNA in the absence or presence of bound
      transcription factors. To do this, we used a novel UV laser-induced protein-DNA
      cross-linking technique, combined with immunochemical and molecular biology
      approaches. Nucleosomes containing one or five GAL4 binding sites were
      reconstituted with hypoacetylated or hyperacetylated core histones. Within these
      reconstituted particles, UV laser-induced histone-DNA cross-linking was found to
      occur only via the nonstructured histone tails and thus presented a unique tool
      for studying histone tail interactions with nucleosomal DNA. Importantly, these
      studies demonstrated that the NH2 tails were not released from nucleosomal DNA
      upon histone acetylation, although some weakening of their interactions was
      observed at elevated ionic strengths. Moreover, the binding of up to five GAL4-AH
      dimers to nucleosomes occupying the central 90 bp occurred without displacement
      of the histone NH2 tails from DNA. GAL4-AH binding perturbed the interaction of
      each histone tail with nucleosomal DNA to different degrees. However, in all
      cases, greater than 50% of the interactions between the histone tails and DNA was
      retained upon GAL4-AH binding, even if the tails were highly acetylated. These
      data illustrate an interaction of acetylated or nonacetylated histone tails with
      DNA that persists in the presence of simultaneously bound transcription factors.

PMID- 9774647
TI  - Glucocorticoid receptor, C/EBP, HNF3, and protein kinase A coordinately activate
      the glucocorticoid response unit of the carbamoylphosphate synthetase I gene.
AB  - A single far-upstream enhancer is sufficient to confer hepatocyte-specific,
      glucocorticoid- and cyclic AMP-inducible periportal expression to the
      carbamoylphosphate synthetase I (CPS) gene. To identify the mechanism of hormone
      dependent activation, the composition and function of the enhancer have been
      analyzed. DNase I protection and gel mobility shift assays revealed the presence
      of a cyclic AMP response element, a glucocorticoid response element (GRE), and
      several sites for the liver-enriched transcription factor families HNF3 and
      C/EBP. The in vivo relevance of the transcription factors interacting with the
      enhancer in the regulation of CPS expression in the liver was assessed by the
      analysis of knockout mice. A strong reduction of CPS mRNA levels was observed in
      glucocorticoid receptor- and C/EBPalpha-deficient mice, whereas the CPS mRNA was
      normally expressed in C/EBPbeta knockout mice and in HNF3alpha and -gamma double
      knockout mice. (The role of HNFbeta could not be assessed, because the
      corresponding knockout mice die at embryonic day 10). In hepatoma cells, most of
      the activity of the enhancer is contained within a 103-bp fragment, which depends
      for its activity on the simultaneous occupation of the GRE, HNF3, and C/EBP
      sites, thus meeting the requirement of a glucocorticoid response unit. In
      fibroblast-like CHO cells, on the other hand, the GRE in the CPS enhancer does
      not cooperate with the C/EBP and HNF3 elements in transactivation of the CPS
      promoter. In both hepatoma and CHO cells, stimulation of expression by cyclic AMP
      depends mainly on the integrity of the glucocorticoid pathway, demonstrating
      cross talk between this pathway and the cyclic AMP (protein kinase A) pathway.

PMID- 9774648
TI  - Viral oncoproteins discriminate between p53 and the p53 homolog p73.
AB  - p73 is a recently identified member of the p53 family. Previously it was shown
      that p73 can, when overproduced in p53-defective tumor cells, activate p53
      responsive promoters and induce apoptosis. In this report we describe the
      generation of anti-p73 monoclonal antibodies and confirm that two previously
      described p73 isoforms are produced in mammalian cells. Furthermore, we show that
      these two isoforms can bind to canonical p53 DNA-binding sites in electrophoretic
      mobility shift assays. Despite the high degree of similarity between p53 and p73,
      we found that adenovirus E1B 55K, simian virus 40 T, and human papillomavirus E6
      do not physically interact with p73. The observation that viral oncoproteins
      discriminate between p53 and p73 suggests that the functions of these two
      proteins may differ under physiological conditions. Furthermore, they suggest
      that inactivation of p73 may not be required for transformation.

PMID- 9774649
TI  - RhoA-binding kinase alpha translocation is facilitated by the collapse of the
      vimentin intermediate filament network.
AB  - The regulation of morphological changes in eukaryotic cells is a complex process
      involving major components of the cytoskeleton including actin microfilaments,
      microtubules, and intermediate filaments (IFs). The putative effector of RhoA,
      RhoA-binding kinase alpha (ROKalpha), is a serine/threonine kinase that has been
      implicated in the reorganization of actin filaments and in myosin contractility.
      Here, we show that ROKalpha also directly affects the structural integrity of
      IFs. Overexpression of active ROKalpha, like that of RhoA, caused the collapse of
      filamentous vimentin, a type III IF. A RhoA-binding-deficient, kinase-inactive
      ROKalpha inhibited the collapse of vimentin IFs induced by RhoA in HeLa cells. In
      vitro, ROKalpha bound and phosphorylated vimentin at its head-rod domain, thereby
      inhibiting the assembly of vimentin. ROKalpha colocalized predominantly with the
      filamentous vimentin network, which remained intact in serum-starved cells.
      Treatment of cells with vinblastine, a microtubule-disrupting agent, also
      resulted in filamentous vimentin collapse and concomitant ROKalpha translocation
      to the cell periphery. ROKalpha translocation did not occur when the vimentin
      network remained intact in vinblastine-treated cells at 4 degreesC or in the
      presence of the dominant-negative RhoAN19 mutant. Transient translocation of
      ROKalpha was also observed in cells subjected to heat shock, which caused the
      disassembly of the vimentin network. Thus, the translocation of ROKalpha to the
      cell periphery upon overexpression of RhoAV14 or growth factor treatment is
      associated with disassembly of vimentin IFs. These results indicate that Rho
      effectors known to act on microfilaments may be involved in regulating the
      assembly of IFs. Vimentin when phosphorylated also exhibits reduced affinity for
      the inactive ROKalpha. The translocation of ROKalpha from IFs to the cell
      periphery upon action by activated RhoA and ROKalpha suggests that ROKalpha may
      initiate its own cascade of activation.

PMID- 9774650
TI  - Heat shock element architecture is an important determinant in the temperature
      and transactivation domain requirements for heat shock transcription factor.
AB  - The baker's yeast Saccharomyces cerevisiae possesses a single gene encoding heat
      shock transcription factor (HSF), which is required for the activation of genes
      that participate in stress protection as well as normal growth and viability.
      Yeast HSF (yHSF) contains two distinct transcriptional activation regions located
      at the amino and carboxyl termini. Activation of the yeast metallothionein gene,
      CUP1, depends on a nonconsensus heat shock element (HSE), occurs at higher
      temperatures than other heat shock-responsive genes, and is highly dependent on
      the carboxyl-terminal transactivation domain (CTA) of yHSF. The results described
      here show that the noncanonical (or gapped) spacing of GAA units in the CUP1 HSE
      (HSE1) functions to limit the magnitude of CUP1 transcriptional activation in
      response to heat and oxidative stress. The spacing in HSE1 modulates the
      dependence for transcriptional activation by both stresses on the yHSF CTA.
      Furthermore, a previously uncharacterized HSE in the CUP1 promoter, HSE2,
      modulates the magnitude of the transcriptional activation of CUP1, via HSE1, in
      response to stress. In vitro DNase I footprinting experiments suggest that the
      occupation of HSE2 by yHSF strongly influences the manner in which yHSF occupies
      HSE1. Limited proteolysis assays show that HSF adopts a distinct protease
      sensitive conformation when bound to the CUP1 HSE1, providing evidence that the
      HSE influences DNA-bound HSF conformation. Together, these results suggest that
      CUP1 regulation is distinct from that of other classic heat shock genes through
      the interaction of yHSF with two nonconsensus HSEs. Consistent with this view, we
      have identified other gene targets of yHSF containing HSEs with sequence and
      spacing features similar to those of CUP1 HSE1 and show a correlation between the
      spacing of the GAA units and the relative dependence on the yHSF CTA.

PMID- 9774651
TI  - The mitochondrial permeability transition is required for tumor necrosis factor
      alpha-mediated apoptosis and cytochrome c release.
AB  - This study assesses the controversial role of the mitochondrial permeability
      transition (MPT) in apoptosis. In primary rat hepatocytes expressing an IkappaB
      superrepressor, tumor necrosis factor alpha (TNFalpha) induced apoptosis as shown
      by nuclear morphology, DNA ladder formation, and caspase 3 activation. Confocal
      microscopy showed that TNFalpha induced onset of the MPT and mitochondrial
      depolarization beginning 9 h after TNFalpha treatment. Initially, depolarization
      and the MPT occurred in only a subset of mitochondria; however, by 12 h after
      TNFalpha treatment, virtually all mitochondria were affected. Cyclosporin A
      (CsA), an inhibitor of the MPT, blocked TNFalpha-mediated apoptosis and
      cytochrome c release. Caspase 3 activation, cytochrome c release, and apoptotic
      nuclear morphological changes were induced after onset of the MPT and were
      prevented by CsA. Depolarization and onset of the MPT were blocked in hepatocytes
      expressing DeltaFADD, a dominant negative mutant of Fas-associated protein with
      death domain (FADD), or crmA, a natural serpin inhibitor of caspases. In
      contrast, Asp-Glu-Val-Asp-cho, an inhibitor of caspase 3, did not block
      depolarization or onset of the MPT induced by TNFalpha, although it inhibited
      cell death completely. In conclusion, the MPT is an essential component in the
      signaling pathway for TNFalpha-induced apoptosis in hepatocytes which is required
      for both cytochrome c release and cell death and functions downstream of FADD and
      crmA but upstream of caspase 3.

PMID- 9774652
TI  - Cak1 is required for Kin28 phosphorylation and activation in vivo.
AB  - Complete activation of most cyclin-dependent protein kinases (CDKs) requires
      phosphorylation by the CDK-activating kinase (CAK). In the budding yeast,
      Saccharomyces cerevisiae, the major CAK is a 44-kDa protein kinase known as Cak1.
      Cak1 is required for the phosphorylation and activation of Cdc28, a major CDK
      involved in cell cycle control. We addressed the possibility that Cak1 is also
      required for the activation of other yeast CDKs, such as Kin28, Pho85, and Srb10.
      We generated three new temperature-sensitive cak1 mutant strains, which arrested
      at the restrictive temperature with nonuniform budding morphology. All three cak1
      mutants displayed significant synthetic interactions with loss-of-function
      mutations in CDC28 and KIN28. Loss of Cak1 function reduced the phosphorylation
      and activity of both Cdc28 and Kin28 but did not affect the activity of Pho85 or
      Srb10. In the presence of the Kin28 regulatory subunits Ccl1 and Tfb3, Kin28 was
      phosphorylated and activated when coexpressed with Cak1 in insect cells. We
      conclude that Cak1 is required for the activating phosphorylation of Kin28 as
      well as that of Cdc28.

PMID- 9774654
TI  - Selective regulation of apoptosis: the cytotoxic lymphocyte serpin proteinase
      inhibitor 9 protects against granzyme B-mediated apoptosis without perturbing the
      Fas cell death pathway.
AB  - Cytotoxic lymphocytes (CLs) induce caspase activation and apoptosis of target
      cells either through Fas activation or through release of granule cytotoxins,
      particularly granzyme B. CLs themselves resist granule-mediated apoptosis but are
      eventually cleared via Fas-mediated apoptosis. Here we show that the CL
      cytoplasmic serpin proteinase inhibitor 9 (PI-9) can protect transfected cells
      against apoptosis induced by either purified granzyme B and perforin or intact
      CLs. A PI-9 P1 mutant (Glu to Asp) is a 100-fold-less-efficient granzyme B
      inhibitor that no longer protects against granzyme B-mediated apoptosis. PI-9 is
      highly specific for granzyme B because it does not inhibit eight of the nine
      caspases tested or protect transfected cells against Fas-mediated apoptosis. In
      contrast, the P1(Asp) mutant is an effective caspase inhibitor that protects
      against Fas-mediated apoptosis. We propose that PI-9 shields CLs specifically
      against misdirected granzyme B to prevent autolysis or fratricide, but it does
      not interfere with homeostatic deletion via Fas-mediated apoptosis.

PMID- 9774653
TI  - Yeast Los1p has properties of an exportin-like nucleocytoplasmic transport factor
      for tRNA.
AB  - Saccharomyces cerevisiae Los1p, which is genetically linked to the nuclear pore
      protein Nsp1p and several tRNA biogenesis factors, was recently grouped into the
      family of importin/karyopherin-beta-like proteins on the basis of its sequence
      similarity. In a two-hybrid screen, we identified Nup2p as a nucleoporin
      interacting with Los1p. Subsequent purification of Los1p from yeast demonstrates
      its physical association not only with Nup2p but also with Nsp1p. By the use of
      the Gsp1p-G21V mutant, Los1p was shown to preferentially bind to the GTP-bound
      form of yeast Ran. Furthermore, overexpression of full-length or N-terminally
      truncated Los1p was shown to have dominant-negative effects on cell growth and
      different nuclear export pathways. Finally, Los1p could interact with Gsp1p-GTP,
      but only in the presence of tRNA, as revealed in an indirect in vitro binding
      assay. These data confirm the homology between Los1p and the recently identified
      human exportin for tRNA and reinforce the possibility of a role for Los1p in
      nuclear export of tRNA in yeast.

PMID- 9774655
TI  - The middle subunit of replication protein A contacts growing RNA-DNA primers in
      replicating simian virus 40 chromosomes.
AB  - The eukaryotic single-stranded DNA binding protein replication protein A (RPA)
      participates in major DNA transactions. RPA also interacts through its middle
      subunit (Rpa2) with regulators of the cell division cycle and of the response to
      DNA damage. A specific contact between Rpa2 and nascent simian virus 40 DNA was
      revealed by in situ UV cross-linking. The dynamic attributes of the cross-linked
      DNA, its size distribution, its RNA primer content, and its  replication fork
      polarity were determined [corrected]. These data suggest that Rpa2 contacts the
      early DNA chain intermediates synthesized by DNA polymerase alpha-primase (RNA
      DNA primers) but not more advanced products. Possible signaling functions of Rpa2
      are discussed, and current models of eukaryotic lagging-strand DNA synthesis are
      evaluated in view of our results.

PMID- 9774656
TI  - The RAG-HMG1 complex enforces the 12/23 rule of V(D)J recombination specifically
      at the double-hairpin formation step.
AB  - A central unanswered question concerning the initial phases of V(D)J
      recombination has been at which step the 12/23 rule applies. This rule, which
      governs which variable (V), diversity (D), and joining (J) segments are able to
      pair during recombination, could operate at the level of signal sequence synapsis
      after RAG-HMG1 complex binding, signal nicking, or signal hairpin formation. It
      has also been unclear whether additional proteins are required to achieve
      adherence to the 12/23 rule. We developed a novel system for the detailed
      biochemical analysis of the 12/23 rule by using an oligonucleotide-based
      substrate that can include two signals. Under physiologic conditions, we found
      that the complex of RAG1, RAG2, and HMG1 can successfully recapitulate the 12/23
      rule with the same specificity as that seen intracellularly and in crude
      extracts. The cleavage complex can bind and nick 12x12 and 23x23 substrates as
      well as 12x23 substrates. However, hairpin formation occurs at both of the
      signals only on 12x23 substrates. Moreover, under physiologic conditions, the
      presence of a partner 23-bp spacer suppresses single-site hairpin formation at a
      12-bp spacer and vice versa. Hence, this study illustrates that synapsis
      suppresses single-site reactions, thereby explaining the high physiologic ratio
      of paired versus unpaired V(D)J recombination events in lymphoid cells.

PMID- 9774657
TI  - Functional cooperation of the interleukin-2 receptor beta chain and Jak1 in
      phosphatidylinositol 3-kinase recruitment and phosphorylation.
AB  - Phosphatidylinositol 3-kinase (PI 3-K) plays an important role in signaling via a
      wide range of receptors such as those for antigen, growth factors, and a number
      of cytokines, including interleukin-2 (IL-2). PI 3-K has been implicated in both
      IL-2-induced proliferation and prevention of apoptosis. A number of potential
      mechanisms for the recruitment of PI 3-K to the IL-2 receptor have been proposed.
      We now have found that tyrosine residues in the IL-2 receptor beta chain (IL
      2Rbeta) are unexpectedly not required for the recruitment of the p85 component of
      PI 3-K. Instead, we find that Jak1, which associates with membrane-proximal
      regions of the IL-2Rbeta cytoplasmic domain, is essential for efficient IL-2Rbeta
      p85 interaction, although some IL-2Rbeta-p85 association can be seen in the
      absence of Jak1. We also found that Jak1 interacts with p85 in the absence of IL
      2Rbeta and that IL-2Rbeta and Jak1 cooperate for the efficient recruitment and
      tyrosine phosphorylation of p85. This is the first report of a PI 3-K-Jak1
      interaction, and it implicates Jak1 in an essential IL-2 signaling pathway
      distinct from the activation of STAT proteins.

PMID- 9774658
TI  - Targeted inactivation of mouse RAD52 reduces homologous recombination but not
      resistance to ionizing radiation.
AB  - The RAD52 epistasis group is required for recombinational repair of double-strand
      breaks (DSBs) and shows strong evolutionary conservation. In Saccharomyces
      cerevisiae, RAD52 is one of the key members in this pathway. Strains with
      mutations in this gene show strong hypersensitivity to DNA-damaging agents and
      defects in recombination. Inactivation of the mouse homologue of RAD52 in
      embryonic stem (ES) cells resulted in a reduced frequency of homologous
      recombination. Unlike the yeast Scrad52 mutant, MmRAD52(-/-) ES cells were not
      hypersensitive to agents that induce DSBs. MmRAD52 null mutant mice showed no
      abnormalities in viability, fertility, and the immune system. These results show
      that, as in S. cerevisiae, MmRAD52 is involved in recombination, although the
      repair of DNA damage is not affected upon inactivation, indicating that MmRAD52
      may be involved in certain types of DSB repair processes and not in others. The
      effect of inactivating MmRAD52 suggests the presence of genes functionally
      related to MmRAD52, which can partly compensate for the absence of MmRad52
      protein.

PMID- 9774659
TI  - Homologous recombination, but not DNA repair, is reduced in vertebrate cells
      deficient in RAD52.
AB  - Rad52 plays a pivotal role in double-strand break (DSB) repair and genetic
      recombination in Saccharomyces cerevisiae, where mutation of this gene leads to
      extreme X-ray sensitivity and defective recombination. Yeast Rad51 and Rad52
      interact, as do their human homologues, which stimulates Rad51-mediated DNA
      strand exchange in vitro, suggesting that Rad51 and Rad52 act cooperatively. To
      define the role of Rad52 in vertebrates, we generated RAD52(-/-) mutants of the
      chicken B-cell line DT40. Surprisingly, RAD52(-/-) cells were not hypersensitive
      to DNA damages induced by gamma-irradiation, methyl methanesulfonate, or cis
      platinum(II)diammine dichloride (cisplatin). Intrachromosomal recombination,
      measured by immunoglobulin gene conversion, and radiation-induced Rad51 nuclear
      focus formation, which is a putative intermediate step during recombinational
      repair, occurred as frequently in RAD52(-/-) cells as in wild-type cells.
      Targeted integration frequencies, however, were consistently reduced in RAD52(-/
      ) cells, showing a clear role for Rad52 in genetic recombination. These findings
      reveal striking differences between S. cerevisiae and vertebrates in the
      functions of RAD51 and RAD52.

PMID- 9774660
TI  - Residues in the Swi5 zinc finger protein that mediate cooperative DNA binding
      with the Pho2 homeodomain protein.
AB  - The Swi5 zinc finger and the Pho2 homeodomain DNA-binding proteins bind
      cooperatively to the HO promoter. Pho2 (also known as Bas2 or Grf10) activates
      transcription of diverse genes, acting with multiple distinct DNA-binding
      proteins. We have performed a genetic screen to identify amino acid residues in
      Swi5 that are required for synergistic transcriptional activation of a reporter
      construct in vivo. Nine unique amino acid substitutions within a 24-amino-acid
      region of Swi5, upstream of the DNA-binding domain, reduce expression of
      promoters that require both Swi5 and Pho2 for activation. In vitro DNA binding
      experiments show that the mutant Swi5 proteins bind DNA normally, but some mutant
      Swi5 proteins (resulting from SWI5* mutations) show reduced cooperative DNA
      binding with Pho2. In vivo experiments show that these SWI5* mutations sharply
      reduce expression of promoters that require both SWI5 and PHO2, while expression
      of promoters that require SWI5 but are PHO2 independent is largely unaffected.
      This suggests that these SWI5* mutations do not affect the ability of Swi5 to
      bind DNA or activate transcription but specifically affect the region of Swi5
      required for interaction with Pho2. Two-hybrid experiments show that amino acids
      471 to 513 of Swi5 are necessary and sufficient for interaction with Pho2 and
      that the SWI5* point mutations cause a severe reduction in this two-hybrid
      interaction. Analysis of promoter activation by these mutants suggests that this
      small region of Swi5 has at least two distinct functions, conferring specificity
      for activation of the HO promoter and for interaction with Pho2.

PMID- 9774661
TI  - Identification of DNA recognition sequences and protein interaction domains of
      the multiple-Zn-finger protein Roaz.
AB  - Roaz, a rat C2H2 zinc finger protein, plays a role in the regulation of olfactory
      neuronal differentiation through its interaction with the Olf-1/EBF transcription
      factor family. An additional role for the Roaz/Olf-1/EBF heterodimeric protein is
      suggested by its ability to regulate gene activation at a distinct promoter
      lacking Olf-1/EBF-binding sites. Using an in vitro binding-site selection assay
      (Selex), we demonstrate that Roaz protein binds to novel inverted perfect or
      imperfect repeats of GCACCC separated by 2 bp. We show that Roaz is capable of
      binding to a canonical consensus recognition sequence with high affinity (Kd = 3
      nM). Analysis of the structural requirement for protein dimerization and DNA
      binding by Roaz reveals the role of specific zinc finger motifs in the Roaz
      protein for homodimerization and heterodimerization with the Olf-1/EBF
      transcription factor. The DNA-binding domain of Roaz is mapped to the N-terminal
      277 amino acids, containing the first seven zinc finger motifs, which confers
      weak monomeric binding to a single half site and a stronger dimeric binding to
      the inverted repeat in a binding-site-dependent manner. Full-length protein can
      form dimers on both the inverted repeat and direct repeat but not on a single
      half site. These findings support the role of the TFIIIA-type Zn fingers in both
      protein-protein interaction and protein-DNA interaction and suggest distinct
      functions for specific motifs in proteins with a large number of zinc finger
      structures.

PMID- 9774662
TI  - The human ARF cell cycle regulatory gene promoter is a CpG island which can be
      silenced by DNA methylation and down-regulated by wild-type p53.
AB  - The INK4a/ARF locus encodes two proteins involved in tumor suppression in a
      manner virtually unique in mammalian cells. Distinct first exons, driven from
      separate promoters, splice onto a common exon 2 and 3 but utilize different
      reading frames to produce two completely distinct proteins, both of which play
      roles in cell cycle control. INK4a, a critical element of the retinoblastoma gene
      pathway, binds to and inhibits the activities of CDK4 and CDK6, while ARF, a
      critical element of the p53 pathway, increases the level of functional p53 via
      interaction with MDM2. Here we clone and characterize the promoter of the human
      ARF gene and show that it is a CpG island characteristic of a housekeeping gene
      which contains numerous Sp1 sites. Both ARF and INK4a are coordinately expressed
      in cells except when their promoter regions become de novo methylated. In one of
      these situations, ARF transcription could be reactivated by treatment with the
      DNA methylation inhibitor 5-aza-2'-deoxycytidine, and the reactivation kinetics
      of ARF and INK4a were found to differ slightly in a cell line in which both genes
      were silenced by methylation. The ARF promoter was also found to be highly
      responsive to E2F1 expression, in keeping with previous results at the RNA level.
      Lastly, transcription from the ARF promoter was down-regulated by wild-type p53
      expression, and the magnitude of the effect correlated with the status of the
      endogenous p53 gene. This finding points to the existence of an autoregulatory
      feedback loop between p53, MDM2, and ARF, aimed at keeping p53 levels in check.

PMID- 9774663
TI  - Intracisternal A-particle element transposition into the murine beta
      glucuronidase gene correlates with loss of enzyme activity: a new model for beta
      glucuronidase deficiency in the C3H mouse.
AB  - The severity of human mucopolysaccharidosis type VII (MPS VII), or Sly syndrome,
      depends on the relative activity of the enzyme beta-glucuronidase. Loss of beta
      glucuronidase activity can cause hydrops fetalis, with in utero or postnatal
      death of the patient. In this report, we show that beta-glucuronidase activity is
      not detectable by a standard fluorometric assay in C3H/HeOuJ (C3H) mice
      homozygous for a new mutation, gusmps2J. These gusmps2J/gusmps2J mice are born
      and survive much longer than the previously characterized beta-glucuronidase-null
      B6.C-H-2(bm1)/ByBir-gusmps (gusmps/gusmps) mice. Northern blot analysis of liver
      from gusmps2J/gusmps2J mice demonstrates a 750-bp reduction in size of beta
      glucuronidase mRNA. A 5.4-kb insertion in the Gus-sh nucleotide sequence from
      these mice was localized by Southern blot analysis to intron 8. The ends of the
      inserted sequences were cloned by inverse PCR and revealed an intracisternal A
      particle (IAP) element inserted near the 3' end of the intron. The sequence of
      the long terminal repeat (LTR) regions of the IAP most closely matches that of a
      composite LTR found in transposed IAPs previously identified in the C3H strain.
      The inserted IAP may contribute to diminished beta-glucuronidase activity either
      by interfering with transcription or by destabilizing the message. The resulting
      phenotype is much less severe than that previously described in the gusmps/gusmps
      mouse and provides an opportunity to study MPS VII on a genetic background that
      clearly modulates disease severity.

PMID- 9774664
TI  - Retinoic acid receptor gamma1 (RARgamma1) levels control RARbeta2 expression in
      SK-N-BE2(c) neuroblastoma cells and regulate a differentiation-apoptosis switch.
AB  - Vitamin A and its derivatives (retinoids) have profound effects on the
      proliferation and differentiation of many cell types and are involved in a
      diverse array of developmental and physiological regulatory processes, including
      those responsible for the development of the mature nervous system. Retinoid
      signals are mediated by retinoic acid (RA) receptors (RARs) and retinoid X
      receptors (RXRs), which show distinct spatio-temporal patterns of expression
      during development and in adult tissues. We have used SK-N-BE2(c) neuroblastoma
      cells to study the effects of reciprocal regulation of expression of various
      RARs. We show that in these cells RARgamma1 acts as a repressor of RARbeta2
      transcription in the absence of an agonist. In the presence of RA, the expression
      of RARgamma1 is reduced and that of RARbeta2 is induced. Overexpression of
      RARgamma1 neutralizes the effects of RA on RARbeta induction. Expression of an
      RARgamma1-specific antisense construct leads to the constitutive expression of
      RARbeta2. Although both overexpression of RARgamma1 and its reduction of
      expression can result in inhibition of cell proliferation, they induce different
      morphological changes. Reduction of RARgamma1 (and induction of RARbeta) leads to
      increased apoptosis, whereas RARgamma1 overexpression leads to differentiation in
      the absence of apoptosis. Thus, RARgamma1 appears to control a differentiation
      apoptosis switch in SK-N-BE2(c) neuroblastoma cells.

PMID- 9774665
TI  - Thioredoxin reductase mediates cell death effects of the combination of beta
      interferon and retinoic acid.
AB  - Interferons (IFNs) and retinoids are potent biological response modifiers. By
      using JAK-STAT pathways, IFNs regulate the expression of genes involved in
      antiviral, antitumor, and immunomodulatory actions. Retinoids exert their cell
      growth-regulatory effects via nuclear receptors, which also function as
      transcription factors. Although these ligands act through distinct mechanisms,
      several studies have shown that the combination of IFNs and retinoids
      synergistically inhibits cell growth. We have previously reported that IFN-beta
      all-trans-retinoic acid (RA) combination is a more potent growth suppressor of
      human tumor xenografts in vivo than either agent alone. Furthermore, the IFN-RA
      combination causes cell death in several tumor cell lines in vitro. However, the
      molecular basis for these growth-suppressive actions is unknown. It has been
      suggested that certain gene products, which mediate the antiviral actions of
      IFNs, are also responsible for the antitumor actions of the IFN-RA combination.
      However, we did not find a correlation between their activities and cell death.
      Therefore, we have used an antisense knockout approach to directly identify the
      gene products that mediate cell death and have isolated several genes associated
      with retinoid-IFN-induced mortality (GRIM). In this investigation, we
      characterized one of the GRIM cDNAs, GRIM-12. Sequence analysis suggests that the
      GRIM-12 product is identical to human thioredoxin reductase (TR). TR is
      posttranscriptionally induced by the IFN-RA combination in human breast carcinoma
      cells. Overexpression of GRIM-12 causes a small amount of cell death and further
      enhances the susceptibility of cells to IFN-RA-induced death. Dominant negative
      inhibitors directed against TR inhibit its cell death-inducing functions.
      Interference with TR enzymatic activity led to growth promotion in the presence
      of the IFN-RA combination. Thus, these studies identify a novel function for TR
      in cell growth regulation.

PMID- 9774666
TI  - Two alternatively spliced transcripts from the Drosophila period gene rescue
      rhythms having different molecular and behavioral characteristics.
AB  - The period (per) and timeless (tim) genes encode key components of the circadian
      oscillator in Drosophila melanogaster. The per gene is thought to encode three
      transcripts via differential splicing (types A, B, and C) that give rise to three
      proteins. Since the three per mRNA types were based on the analysis of cDNA
      clones, we tested whether these mRNA types were present in vivo by RNase
      protection assays and reverse transcriptase-mediated PCR. The results show that
      per generates two transcript types that differ only by the presence (type A) or
      absence (type B') of an alternative intron in the 3' untranslated region.
      Transgenic flies containing transgenes that produce only type B' transcripts
      (perB'), type A transcripts (perA), or both transcripts (perG) rescue locomotor
      activity rhythms with average periods of 24.7, 25.4, and 24.4 h, respectively.
      Although no appreciable differences in type A and type B' mRNA cycling were
      observed, a slower accumulation of PER in flies making only type A transcripts
      suggests that the intron affects the translation of per mRNA.

PMID- 9774667
TI  - Preprotein translocase of the outer mitochondrial membrane: molecular dissection
      and assembly of the general import pore complex.
AB  - The preprotein translocase of the outer mitochondrial membrane (Tom) is a
      multisubunit machinery containing receptors and a general import pore (GIP). We
      have analyzed the molecular architecture of the Tom machinery. The receptor Tom22
      stably associates with Tom40, the main component of the GIP, in a complex with a
      molecular weight of approximately 400,000 ( approximately 400K), while the other
      receptors, Tom20 and Tom70, are more loosely associated with this GIP complex and
      can be found in distinct subcomplexes. A yeast mutant lacking both Tom20 and
      Tom70 can still form the GIP complex when sufficient amounts of Tom22 are
      synthesized. Besides the essential proteins Tom22 and Tom40, the GIP complex
      contains three small subunits, Tom5, Tom6, and Tom7. In mutant mitochondria
      lacking Tom6, the interaction between Tom22 and Tom40 is destabilized, leading to
      the dissociation of Tom22 and the generation of a subcomplex of approximately
      100K containing Tom40, Tom7, and Tom5. Tom6 is required to promote but not to
      maintain a stable association between Tom22 and Tom40. The following conclusions
      are suggested. (i) The GIP complex, containing Tom40, Tom22, and three small Tom
      proteins, forms the central unit of the outer membrane import machinery. (ii)
      Tom20 and Tom70 are not essential for the generation of the GIP complex. (iii)
      Tom6 functions as an assembly factor for Tom22, promoting its stable association
      with Tom40.

PMID- 9774668
TI  - Mismatch repair proteins regulate heteroduplex formation during mitotic
      recombination in yeast.
AB  - Mismatch repair (MMR) proteins actively inhibit recombination between diverged
      sequences in both prokaryotes and eukaryotes. Although the molecular basis of the
      antirecombination activity exerted by MMR proteins is unclear, it presumably
      involves the recognition of mismatches present in heteroduplex recombination
      intermediates. This recognition could be exerted during the initial stage of
      strand exchange, during the extension of heteroduplex DNA, or during the
      resolution of recombination intermediates. We previously used an assay system
      based on 350-bp inverted-repeat substrates to demonstrate that MMR proteins
      strongly inhibit mitotic recombination between diverged sequences in
      Saccharomyces cerevisiae. The assay system detects only those events that reverse
      the orientation of the region between the recombination substrates, which can
      occur as a result of either intrachromatid crossover or sister chromatid
      conversion. In the present study we sequenced the products of mitotic
      recombination between 94%-identical substrates in order to map gene conversion
      tracts in wild-type versus MMR-defective yeast strains. The sequence data
      indicate that (i) most recombination occurs via sister chromatid conversion and
      (ii) gene conversion tracts in an MMR-defective strain are significantly longer
      than those in an isogenic wild-type strain. The shortening of conversion tracts
      observed in a wild-type strain relative to an MMR-defective strain suggests that
      at least part of the antirecombination activity of MMR proteins derives from the
      blockage of heteroduplex extension in the presence of mismatches.

PMID- 9774669
TI  - Identification and characterization of a family of mammalian methyl-CpG binding
      proteins.
AB  - Methylation at the DNA sequence 5'-CpG is required for mouse development. MeCP2
      and MBD1 (formerly PCM1) are two known proteins that bind specifically to
      methylated DNA via a related amino acid motif and that can repress transcription.
      We describe here three novel human and mouse proteins (MBD2, MBD3, and MBD4) that
      contain the methyl-CpG binding domain. MBD2 and MBD4 bind specifically to
      methylated DNA in vitro. Expression of MBD2 and MBD4 tagged with green
      fluorescent protein in mouse cells shows that both proteins colocalize with foci
      of heavily methylated satellite DNA. Localization is disrupted in cells that have
      greatly reduced levels of CpG methylation. MBD3 does not bind methylated DNA in
      vivo or in vitro. MBD1, MBD2, MBD3, and MBD4 are expressed in somatic tissues,
      but MBD1 and MBD2 expression is reduced or absent in embryonic stem cells which
      are known to be deficient in MeCP1 activity. The data demonstrate that MBD2 and
      MBD4 bind specifically to methyl-CpG in vitro and in vivo and are therefore
      likely to be mediators of the biological consequences of the methylation signal.

PMID- 9774670
TI  - Poly(A) tail length control in Saccharomyces cerevisiae occurs by message
      specific deadenylation.
AB  - We report that newly synthesized mRNA poly(A) tails are matured to precise
      lengths by the Pab1p-dependent poly(A) nuclease (PAN) of Saccharomyces
      cerevisiae. These results provide evidence for an initial phase of mRNA
      deadenylation that is required for poly(A) tail length control. In RNA 3'-end
      processing extracts lacking PAN, transcripts are polyadenylated to lengths
      exceeding 200 nucleotides. By contrast, in extracts containing PAN, transcripts
      were produced with the expected wild-type poly(A) tail lengths of 60 to 80
      nucleotides. The role for PAN in poly(A) tail length control in vivo was
      confirmed by the finding that mRNAs are produced with longer poly(A) tails in PAN
      deficient yeast strains. Interestingly, wild-type yeast strains were found to
      produce transcripts which varied in their maximal poly(A) tail length, and this
      message-specific length control was lost in PAN-deficient strains. Our data
      support a model whereby mRNAs are polyadenylated by the 3'-end processing
      machinery with a long tail, possibly of default length, and then in a PAN
      dependent manner, the poly(A) tails are rapidly matured to a message-specific
      length. The ability to control the length of the poly(A) tail for newly expressed
      mRNAs has the potential to be an important posttranscriptional regulatory step in
      gene expression.

PMID- 9774671
TI  - Global regulatory functions of Oaf1p and Pip2p (Oaf2p), transcription factors
      that regulate genes encoding peroxisomal proteins in Saccharomyces cerevisiae.
AB  - Two transcription factors, Oaf1p and Pip2p (Oaf2p), are key components in the
      pathway by which several Saccharomyces cerevisiae genes encoding peroxisomal
      proteins are activated in the presence of a fatty acid such as oleate. By
      searching the S. cerevisiae genomic database for the consensus sequence that acts
      as a target for these transcription factors, we identified 40 genes that contain
      a putative Oaf1p-Pip2p binding site in their promoter region. Quantitative
      Northern analysis confirmed that the expression of 22 of the genes identified is
      induced by oleate and that either one or both of these transcription factors are
      required for the activation. In addition to known peroxisomal proteins, the
      regulated genes encode novel peroxisomal proteins, a mitochondrial protein, and
      proteins of unknown location and function. We demonstrate that Oaf1p regulates
      certain genes in the absence of Pip2p and that both of these transcription
      factors play a role in maintaining the glucose-repressed state of one gene.
      Furthermore, we provide evidence that the defined consensus binding site is not
      required for the regulation of certain oleate-responsive genes.

PMID- 9774672
TI  - Novel cofactors and TFIIA mediate functional core promoter selectivity by the
      human TAFII150-containing TFIID complex.
AB  - TATA-binding protein-associated factors (TAFIIs) within TFIID control
      differential gene transcription through interactions with both activators and
      core promoter elements. In particular, TAFII150 contributes to initiator
      dependent transcription through an unknown mechanism. Here, we address whether
      TAFIIs within TFIID are sufficient, in conjunction with highly purified general
      transcription factors (GTFs), for differential core promoter-dependent
      transcription by RNA polymerase II and whether additional cofactors are required.
      We identify the human homologue of Drosophila TAFII150 through cognate cDNA
      cloning and show that it is a tightly associated component of human TFIID. More
      importantly, we demonstrate that the human TAFII150-containing TFIID complex is
      not sufficient, in the context of all purified GTFs and RNA polymerase II, to
      mediate transcription synergism between TATA and initiator elements and initiator
      directed transcription from a TAFII-dependent TATA-less promoter. Therefore,
      TAFII-promoter interactions are not sufficient for the productive core promoter
      selective functions of TFIID. Consistent with this finding, we have partially
      purified novel cofactor activities (TICs) that potentiate the TAFII-mediated
      synergism between TATA and initiator elements (TIC-1) and TAFII-dependent
      transcription from TATA-less promoters (TIC-2 and -3). Furthermore, we
      demonstrate an essential function for TFIIA in TIC- and TAFII-dependent basal
      transcription from a TATA-less promoter. Our results reveal a parallel between
      the basal transcription activity of TAFIIs through core promoter elements and
      TAFII-dependent activator function.

PMID- 9774673
TI  - Dorsal-mediated repression requires the formation of a multiprotein repression
      complex at the ventral silencer.
AB  - Dorsal functions as both an activator and repressor of transcription to determine
      dorsoventral fate in the Drosophila melanogaster embryo. Repression by Dorsal
      requires the corepressor Groucho (Gro) and is mediated by silencers termed
      ventral repression regions (VRRs). A VRR in zerknullt (zen) contains Dorsal
      binding sites as well as an essential element termed AT2. We have identified and
      purified an AT2 DNA binding activity in embryos and shown it to consist of cut
      (ct) and dead ringer (dri) gene products. Studies of loss-of-function mutations
      in ct and dri demonstrate that both genes are required for the activity of the
      AT2 site. Dorsal and Dri both bind Gro, acting cooperatively to recruit it to the
      DNA. Thus, ventral repression may require the formation of a multiprotein complex
      at the VRR. This complex includes Dorsal, Gro, and additional DNA binding
      proteins, which appear to convert Dorsal from an activator to a repressor by
      enabling it to recruit Gro to the template. By showing how binding site context
      can dramatically alter transcription factor function, these findings help clarify
      the mechanisms responsible for the regulatory specificity of transcription
      factors.

PMID- 9774674
TI  - Physical and functional interactions between type I transforming growth factor
      beta receptors and Balpha, a WD-40 repeat subunit of phosphatase 2A.
AB  - We have previously shown that a WD-40 repeat protein, TRIP-1, associates with the
      type II transforming growth factor beta (TGF-beta) receptor. In this report, we
      show that another WD-40 repeat protein, the Balpha subunit of protein phosphatase
      2A, associates with the cytoplasmic domain of type I TGF-beta receptors. This
      association depends on the kinase activity of the type I receptor, is increased
      by coexpression of the type II receptor, which is known to phosphorylate and
      activate the type I receptor, and allows the type I receptor to phosphorylate
      Balpha. Furthermore, Balpha enhances the growth inhibition activity of TGF-beta
      in a receptor-dependent manner. Because Balpha has been characterized as a
      regulator of phosphatase 2A activity, our observations suggest possible
      functional interactions between the TGF-beta receptor complex and the regulation
      of protein phosphatase 2A.

PMID- 9774675
TI  - Regulation of exit from quiescence by p27 and cyclin D1-CDK4.
AB  - The synthesis of cyclin D1 and its assembly with cyclin-dependent kinase 4 (CDK4)
      to form an active complex is a rate-limiting step in progression through the G1
      phase of the cell cycle. Using an activated allele of mitogen-activated protein
      kinase kinase 1 (MEK1), we show that this kinase plays a significant role in
      positively regulating the expression of cyclin D1. This was found both in
      quiescent serum-starved cells and in cells expressing dominant-negative Ras.
      Despite the observation that cyclin D1 is a target of MEK1, in cycling cells,
      activated MEK1, but not cyclin D1, is capable of overcoming a G1 arrest induced
      by Ras inactivation. Either wild-type or catalytically inactive CDK4 cooperates
      with cyclin D1 in reversing the G1 arrest induced by inhibition of Ras activity.
      In quiescent NIH 3T3 cells expressing either ectopic cyclin D1 or activated MEK1,
      cyclin D1 is able to efficiently associate with CDK4; however, the complex is
      inactive. A significant percentage of the cyclin D1-CDK4 complexes are associated
      with p27 in serum-starved activated MEK1 or cyclin D1 cell lines. Reduction of
      p27 levels by expression of antisense p27 allows for S-phase entry from
      quiescence in NIH 3T3 cells expressing ectopic cyclin D1, but not in parental
      cells.

PMID- 9774676
TI  - Interactions of human hMSH2 with hMSH3 and hMSH2 with hMSH6: examination of
      mutations found in hereditary nonpolyposis colorectal cancer.
AB  - Mutations in the human mismatch repair protein hMSH2 have been found to
      cosegregate with hereditary nonpolyposis colorectal cancer (HNPCC). Previous
      biochemical and physical studies have shown that hMSH2 forms specific mispair
      binding complexes with hMSH3 and hMSH6. We have further characterized these
      protein interactions by mapping the contact regions within the hMSH2-hMSH3 and
      the hMSH2-hMSH6 heterodimers. We demonstrate that there are at least two distinct
      interaction regions of hMSH2 with hMSH3 and hMSH2 with hMSH6. Interestingly, the
      interaction regions of hMSH2 with either hMSH3 or hMSH6 are identical and there
      is a coordinated linear orientation of these regions. We examined several
      missense alterations of hMSH2 found in HNPCC kindreds that are contained within
      the consensus interaction regions. None of these missense mutations displayed a
      defect in protein-protein interaction. These data support the notion that these
      HNPCC-associated mutations may affect some other function of the heterodimeric
      complexes than simply the static interaction of hMSH2 with hMSH3 or hMSH2 with
      hMSH6.

PMID- 9774677
TI  - Glycogen synthase kinase 3beta and extracellular signal-regulated kinase
      inactivate heat shock transcription factor 1 by facilitating the disappearance of
      transcriptionally active granules after heat shock.
AB  - Heat shock transcription factor 1 (HSF-1) activates the transcription of heat
      shock genes in eukaryotes. Under normal physiological growth conditions, HSF-1 is
      a monomer. Its transcriptional activity is repressed by constitutive
      phosphorylation. Upon activation, HSF-1 forms trimers, acquires DNA binding
      activity, increases transcriptional activity, and appears as punctate granules in
      the nucleus. In this study, using bromouridine incorporation and confocal laser
      microscopy, we demonstrated that newly synthesized pre-mRNAs colocalize to the
      HSF-1 punctate granules after heat shock, suggesting that these granules are
      sites of transcription. We further present evidence that glycogen synthase kinase
      3beta (GSK-3beta) and extracellular signal-regulated kinase mitogen-activated
      protein kinase (ERK MAPK) participate in the down regulation of HSF-1
      transcriptional activity. Transient increases in the expression of GSK-3beta
      facilitate the disappearance of HSF-1 punctate granules and reduce hsp-70
      transcription after heat shock. We have also shown that ERK is the priming kinase
      for GSK-3beta. Taken together, these results indicate that GSK-3beta and ERK MAPK
      facilitate the inactivation of activated HSF-1 after heat shock by dispersing HSF
      1 from the sites of transcription.

PMID- 9774678
TI  - Substitution of the human beta-spectrin promoter for the human agamma-globin
      promoter prevents silencing of a linked human beta-globin gene in transgenic
      mice.
AB  - During development, changes occur in both the sites of erythropoiesis and the
      globin genes expressed at each developmental stage. Previous work has shown that
      high-level expression of human beta-like globin genes in transgenic mice requires
      the presence of the locus control region (LCR). Models of hemoglobin switching
      propose that the LCR and/or stage-specific elements interact with globin gene
      sequences to activate specific genes in erythroid cells. To test these models, we
      generated transgenic mice which contain the human Agamma-globin gene linked to a
      576-bp fragment containing the human beta-spectrin promoter. In these mice, the
      beta-spectrin Agamma-globin (betasp/Agamma) transgene was expressed at high
      levels in erythroid cells throughout development. Transgenic mice containing a 40
      kb cosmid construct with the micro-LCR, betasp/Agamma-, psibeta-, delta-, and
      beta-globin genes showed no developmental switching and expressed both human
      gamma- and beta-globin mRNAs in erythroid cells throughout development. Mice
      containing control cosmids with the Agamma-globin gene promoter showed
      developmental switching and expressed Agamma-globin mRNA in yolk sac and fetal
      liver erythroid cells and beta-globin mRNA in fetal liver and adult erythroid
      cells. Our results suggest that replacement of the gamma-globin promoter with the
      beta-spectrin promoter allows the expression of the beta-globin gene. We conclude
      that the gamma-globin promoter is necessary and sufficient to suppress the
      expression of the beta-globin gene in yolk sac erythroid cells.

PMID- 9774679
TI  - Identification of a novel slow-muscle-fiber enhancer binding protein, MusTRD1.
AB  - The molecular mechanisms which are responsible for restricting skeletal muscle
      gene expression to specific fiber types, either slow or fast twitch, are unknown.
      As a first step toward defining the components which direct slow-fiber-specific
      gene expression, we identified the sequence elements of the human troponin I slow
      upstream enhancer (USE) that bind muscle nuclear proteins. These include an E
      box, a MEF2 element, and two other elements, USE B1 and USE C1. In vivo analysis
      of a mutation that disrupts USE B1 binding activity suggested that the USE B1
      element is essential for high-level expression in slow-twitch muscles. This
      mutation does not, however, abolish slow-fiber specificity. A similar analysis
      indicated that the USE C1 element may play only a minor role. We report the
      cloning of a novel human USE B1 binding protein, MusTRD1 (muscle TFII-I repeat
      domain-containing protein 1), which is expressed predominantly in skeletal
      muscle. Significantly, MusTRD1 contains two repeat domains which show remarkable
      homology to the six repeat domains of the recently cloned transcription factor
      TFII-I. Furthermore, both TFII-I and MusTRD1 bind to similar but distinct
      sequences, which happen to conform with the initiator (Inr) consensus sequence.
      Given the roles of MEF2 and basic helix-loop-helix (bHLH) proteins in muscle gene
      expression, the similarity of TFII-I and MusTRD1 is intriguing, as TFII-I is
      believed to coordinate the interaction of MADS-box proteins, bHLH proteins, and
      the general transcription machinery.

PMID- 9774680
TI  - Direct interaction of SRY-related protein SOX9 and steroidogenic factor 1
      regulates transcription of the human anti-Mullerian hormone gene.
AB  - For proper male sexual differentiation, anti-Mullerian hormone (AMH) must be
      tightly regulated during embryonic development to promote regression of the
      Mullerian duct. However, the molecular mechanisms specifying the onset of AMH in
      male mammals are not yet clearly defined. A DNA-binding element for the
      steroidogenic factor 1 (SF-1), a member of the orphan nuclear receptor family,
      located in the AMH proximal promoter has recently been characterized and
      demonstrated as being essential for AMH gene activation. However, the requirement
      for a specific promoter environment for SF-1 activation as well as the presence
      of conserved cis DNA-binding elements in the AMH promoter suggest that SF-1 is a
      member of a combinatorial protein-protein and protein-DNA complex. In this study,
      we demonstrate that the canonical SOX-binding site within the human AMH proximal
      promoter can bind the transcription factor SOX9, a Sertoli cell factor closely
      associated with Sertoli cell differentiation and AMH expression. Transfection
      studies with COS-7 cells revealed that SOX9 can cooperate with SF-1 in this
      activation process. In vitro and in vivo protein-binding studies indicate that
      SOX9 and SF-1 interact directly via the SOX9 DNA-binding domain and the SF-1 C
      terminal region, respectively. We propose that the two transcription factors SOX9
      and SF-1 could both be involved in the expression of the AMH gene, in part as a
      result of their respective binding to the AMH promoter and in part because of
      their ability to interact with each other. Our work thus identifies SOX9 as an
      interaction partner of SF-1 that could be involved in the Sertoli cell-specific
      expression of AMH during embryogenesis.

PMID- 9774681
TI  - Integration of growth factor, extracellular matrix, and retinoid signals during
      bronchial epithelial cell differentiation.
AB  - Epithelial cell differentiation is regulated by specific combinations of growth
      factors, hormones, and extracellular matrix (ECM). How these divergent signals
      are integrated is largely unknown. We used primary cultures of normal human
      bronchial epithelial cells (NHBEs) to investigate mechanisms of signal
      integration. In defined, serum-free media, NHBEs undergo mucosecretory
      differentiation only when grown in the presence of retinoids and on the
      appropriate substratum (collagen gels). We identified the retinoic acid receptor
      beta (RARbeta) gene as an early marker of NHBE differentiation. In contrast to
      immortalized cell lines, in NHBEs strong retinoid-induced RARbeta transcription
      occurs only when cells are grown on collagen gels, and it requires new protein
      synthesis and a cis-acting element that maps outside the known RARbeta promoter
      elements. NHBEs grown on collagen gels exhibit reduced epidermal growth factor
      (EGF)-induced Raf, MEK, and mitogen-activated protein kinase (MAPK) activity.
      This correlates with a specific inability to achieve high levels of p66(SHC)
      tyrosyl phosphorylation and association of p66(SHC) with GRB2, despite high
      levels of EGF receptor (EGFR) autophosphorylation. Notably, inhibition of EGFR or
      MEK/MAPK activation replaces the ECM requirement for RARbeta induction. Our
      results strongly suggest that a key mechanism by which specific ECMs facilitate
      retinoid-induced mucosecretory differentiation of NHBEs is by restricting the
      level of EGFR-dependent MEK/MAPK activation evoked by autocrine and/or paracrine
      EGFR ligands.

PMID- 9774682
TI  - Cell cycle-regulated expression of mammalian CDC6 is dependent on E2F.
AB  - The E2F transcription factors are essential regulators of cell growth in
      multicellular organisms, controlling the expression of a number of genes whose
      products are involved in DNA replication and cell proliferation. In Saccharomyces
      cerevisiae, the MBF and SBF transcription complexes have functions similar to
      those of E2F proteins in higher eukaryotes, by regulating the timed expression of
      genes implicated in cell cycle progression and DNA synthesis. The CDC6 gene is a
      target for MBF and SBF-regulated transcription. S. cerevisiae Cdc6p induces the
      formation of the prereplication complex and is essential for initiation of DNA
      replication. Interestingly, the Cdc6p homolog in Schizosaccharomyces pombe,
      Cdc18p, is regulated by DSC1, the S. pombe homolog of MBF. By cloning the
      promoter for the human homolog of Cdc6p and Cdc18p, we demonstrate here that the
      cell cycle-regulated transcription of this gene is dependent on E2F. In vivo
      footprinting data demonstrate that the identified E2F sites are occupied in
      resting cells and in exponentially growing cells, suggesting that E2F is
      responsible for downregulating the promoter in early phases of the cell cycle and
      the subsequent upregulation when cells enter S phase. Our data also demonstrate
      that the human CDC6 protein (hCDC6) is essential and limiting for DNA synthesis,
      since microinjection of an anti-CDC6 rabbit antiserum blocks DNA synthesis and
      CDC6 cooperates with cyclin E to induce entry into S phase in cotransfection
      experiments. Furthermore, E2F is sufficient to induce expression of the
      endogenous CDC6 gene even in the absence of de novo protein synthesis. In
      conclusion, our results provide a direct link between regulated progression
      through G1 controlled by the pRB pathway and the expression of proteins essential
      for the initiation of DNA replication.

PMID- 9774683
TI  - The RafC1 cysteine-rich domain contains multiple distinct regulatory epitopes
      which control Ras-dependent Raf activation.
AB  - Activation of c-Raf-1 (referred to as Raf) by Ras is a pivotal step in mitogenic
      signaling. Raf activation is initiated by binding of Ras to the regulatory N
      terminus of Raf. While Ras binding to residues 51 to 131 is well understood, the
      role of the RafC1 cysteine-rich domain comprising residues 139 to 184 has
      remained elusive. To resolve the function of the RafC1 domain, we have performed
      an exhaustive surface scanning mutagenesis. In our study, we defined a high
      resolution map of multiple distinct functional epitopes within RafC1 that are
      required for both negative control of the kinase and the positive function of the
      protein. Activating mutations in three different epitopes enhanced Ras-dependent
      Raf activation, while only some of these mutations markedly increased Raf basal
      activity. One contiguous inhibitory epitope consisting of S177, T182, and M183
      clearly contributed to Ras-Raf binding energy and represents the putative Ras
      binding site of the RafC1 domain. The effects of all RafC1 mutations on Ras
      binding and Raf activation were independent of Ras lipid modification. The
      inhibitory mutation L160A is localized to a position analogous to the phorbol
      ester binding site in the protein kinase C C1 domain, suggesting a function in
      cofactor binding. Complete inhibition of Ras-dependent Raf activation was
      achieved by combining mutations K144A and L160A, which clearly demonstrates an
      absolute requirement for correct RafC1 function in Ras-dependent Raf activation.

PMID- 9774684
TI  - Akt-dependent and -independent survival signaling pathways utilized by insulin
      like growth factor I.
AB  - Protein kinase B (PKB)/Akt is implicated in survival signaling in a wide variety
      of cells including fibroblasts and epithelial and neuronal cells. We and others
      have described a linear survival signaling cascade used by insulinlike growth
      factor I (IGF-I) that consists of the IGF-I receptor, phosphoinositide 3-kinase
      (PI3 kinase), Akt, and Bad. Activation of this pathway can be sufficient to
      protect cells from apoptosis. However, previous work had not determined whether
      this pathway is invariably necessary for protection from apoptosis or whether
      there are alternative survival signaling pathways. In this communication, we
      report the existence of two survival signaling pathways, one dependent on PI3
      kinase and Akt and the other independent of these enzymes. We found that survival
      signaling initiated by IGF-I treatment of Rat-1 cells could be blocked by
      overexpression of a dominant negative kinase-deficient Akt (K179A) as well as by
      wortmannin. This demonstrates a survival signaling pathway dependent on PI3
      kinase and Akt. However, when IGF-I receptors were overexpressed in a Rat-1
      background (RIG cells), an alternative pathway became apparent, in which survival
      mediated by IGF-I was no longer sensitive to wortmannin or to overexpression of
      dominant negative Akt, even though Akt activation and Bad phosphorylation were
      still wortmannin sensitive. Experiments with inhibitors of RNA synthesis showed
      that transcriptional activation is dispensable for this alternative PI3
      kinase/Akt-independent survival signaling. These findings demonstrate the
      existence of a new survival signaling pathway independent of PI3 kinase, Akt, and
      new transcription and which is evident in fibroblasts overexpressing the IGF-I
      receptor.

PMID- 9774685
TI  - Inactivation of DNA-dependent protein kinase by protein kinase Cdelta:
      implications for apoptosis.
AB  - Protein kinase Cdelta (PKCdelta) is proteolytically cleaved and activated at the
      onset of apoptosis induced by DNA-damaging agents, tumor necrosis factor, and
      anti-Fas antibody. A role for PKCdelta in apoptosis is supported by the finding
      that overexpression of the catalytic fragment of PKCdelta (PKCdelta CF) in cells
      is associated with the appearance of certain characteristics of apoptosis.
      However, the functional relationship between PKCdelta cleavage and induction of
      apoptosis is unknown. The present studies demonstrate that PKCdelta associates
      constitutively with the DNA-dependent protein kinase catalytic subunit (DNA
      PKcs). The results show that PKCdelta CF phosphorylates DNA-PKcs in vitro.
      Interaction of DNA-PKcs with PKCdelta CF inhibits the function of DNA-PKcs to
      form complexes with DNA and to phosphorylate its downstream target, p53. The
      results also demonstrate that cells deficient in DNA-PK are resistant to
      apoptosis induced by overexpressing PKCdelta CF. These findings support the
      hypothesis that functional interactions between PKCdelta and DNA-PK contribute to
      DNA damage-induced apoptosis.

PMID- 9774686
TI  - A Ras-dependent pathway regulates RNA polymerase II phosphorylation in cardiac
      myocytes: implications for cardiac hypertrophy.
AB  - Despite extensive evidence implicating Ras in cardiac muscle hypertrophy, the
      mechanisms involved are unclear. We previously reported that Ras, through an
      effector-like function of Ras GTPase-activating protein (GAP) in neonatal cardiac
      myocytes (M. Abdellatif et al., J. Biol. Chem. 269:15423-15426, 1994; M.
      Abdellatif and M. D. Schneider, J. Biol. Chem. 272:527-533, 1997), can up
      regulate expression from a comprehensive set of promoters, including both cardiac
      cell-specific and constitutive ones. To investigate the mechanism(s) underlying
      these earlier findings, we have used recombinant adenoviruses harboring a
      dominant negative Ras (17N Ras) allele or the N-terminal domain of GAP (nGAP),
      responsible for the Ras-like effector function. Inhibition of endogenous Ras
      reduced basal levels of [3H]uridine and [3H]phenylalanine incorporation into
      total RNA, mRNA, and protein, with parallel changes in apparent cell size. In
      addition, 17N Ras markedly inhibited phosphorylation of the C-terminal domain
      (CTD) of RNA polymerase II (pol II), known to regulate transcript elongation,
      accompanied by down-regulation of its principal kinase, cyclin-dependent kinase 7
      (Cdk7). In contrast, nGAP elicited the opposite effects on each of these
      parameters. Furthermore, cotransfection of constitutively active Ras (12R Ras)
      with wild-type pol II, rather than a truncated mutant lacking the CTD,
      demonstrated that Ras activation of transcription was dependent on the pol II
      CTD. Consistent with a potential role for this pathway in the development of
      cardiac myocyte hypertrophy, alpha1-adrenergic stimulation similarly enhanced pol
      II phosphorylation and Cdk7 expression, where both effects were inhibited by
      dominant negative Ras, while pressure overload hypertrophy led to an increase in
      both hyperphosphorylated and hypophosphorylated pol II in addition to Cdk7.

PMID- 9774687
TI  - DNA supercoiling factor localizes to puffs on polytene chromosomes in Drosophila
      melanogaster.
AB  - DNA supercoiling factor (SCF) was first identified in silkworm as a protein that
      generates negative supercoils in DNA in conjunction with eukaryotic topoisomerase
      II. To analyze the in vivo role of the factor, we cloned a cDNA encoding
      Drosophila melanogaster SCF. Northern analysis revealed 1.6- and 1.8-kb mRNAs
      throughout development. The longer mRNA contains an open reading frame that
      shares homology with mouse reticulocalbin whereas the shorter one encodes a
      truncated version lacking the N-terminal signal peptide-like sequence. An
      antibody against SCF detected a 45-kDa protein in the cytoplasmic fraction and a
      30-kDa protein in the nuclear fraction of embryonic extracts. Immunoprecipitation
      suggests that the 30-kDa protein interacts with topoisomerase II in the nucleus,
      and hence that it is a functional form of SCF. Immunostaining of blastoderm
      embryos showed that SCF is present in nuclei during interphase but is excluded
      from mitotic chromosomes. In larvae, the antibody stained the nuclei of several
      tissues including a posterior part of the salivary gland. This latter staining
      was associated with natural or ecdysteroid-induced puffs on polytene chromosomes.
      Upon heat treatment of larvae, the staining on the endogenous puffs disappeared,
      and strong staining appeared on heat shock puffs. These results implicate SCF in
      gene expression.

PMID- 9774688
TI  - Cloning and characterization of mouse RIP140, a corepressor for nuclear orphan
      receptor TR2.
AB  - The mouse homologue of the human receptor-interacting protein 140 (RIP140) was
      isolated from a mouse embryonic cDNA library in yeast two-hybrid screening
      experiments by using the ligand binding domain (LBD) of nuclear orphan receptor
      TR2 as the bait. The receptor-interacting domains of mouse RIP140 were mapped to
      the regions containing the LXXLL motif (where L is leucine and X is any amino
      acid), and the RIP140-interacting domain of TR2 was mapped to its C-terminal 10-
      to 20-amino-acid sequence, a putative activation function 2 (AF-2) region. In a
      GAL4 reporter system and a reporter driven by the proximal region of the TR2
      promoter, RIP140 functioned as a corepressor for both a GAL4 DNA binding domain
      (BD)-TR2 fusion and the wild-type receptor. When tethered to the BD of GAL4,
      RIP140 exerted a trans-repressive effect on the GAL4 reporter. In addition,
      RIP140 suppressed the retinoic acid (RA) receptor-mediated RA induction in a dose
      dependent manner. Finally, it was demonstrated that in the presence of RIP140, a
      cytosolic, green fluorescent protein-tagged TR2 LBD translocated into the
      nucleus, and TR2 and RIP140 were coimmunoprecipitated from the cell extract,
      indicating that the interaction between RIP140 and the LBD of TR2 occurred in
      vivo. The potential biological role of RIP140 in TR2-modulated transcriptional
      activity is discussed.

PMID- 9774689
TI  - The human U5-220kD protein (hPrp8) forms a stable RNA-free complex with several
      U5-specific proteins, including an RNA unwindase, a homologue of ribosomal
      elongation factor EF-2, and a novel WD-40 protein.
AB  - The human small nuclear ribonucleoprotein (snRNP) U5 is biochemically the most
      complex of the snRNP particles, containing not only the Sm core proteins but also
      10 particle-specific proteins. Several of these proteins have sequence motifs
      which suggest that they participate in conformational changes of RNA and protein.
      Together, the specific proteins comprise 85% of the mass of the U5 snRNP
      particle. Therefore, protein-protein interactions should be highly important for
      both the architecture and the function of this particle. We investigated protein
      protein interactions using both native and recombinant U5-specific proteins.
      Native U5 proteins were obtained by dissociation of U5 snRNP particles with the
      chaotropic salt sodium thiocyanate. A stable, RNA-free complex containing the 116
      kDa EF-2 homologue (116kD), the 200kD RNA unwindase, the 220kD protein, which is
      the orthologue of the yeast Prp8p protein, and the U5-40kD protein was detected
      by sedimentation analysis of the dissociated proteins. By cDNA cloning, we show
      that the 40kD protein is a novel WD-40 repeat protein and is thus likely to
      mediate regulated protein-protein interactions. Additional biochemical analyses
      demonstrated that the 220kD protein binds simultaneously to the 40- and the 116kD
      proteins and probably also to the 200kD protein. Since the 220kD protein is also
      known to contact both the pre-mRNA and the U5 snRNA, it is in a position to relay
      the functional state of the spliceosome to the other proteins in the complex and
      thus modulate their activity.

PMID- 9774690
TI  - Characterization of novel parent-specific epigenetic modifications upstream of
      the imprinted mouse H19 gene.
AB  - Genomic imprinting results in parent-specific monoallelic expression of a small
      number of genes in mammals. The identity of imprints is unknown, but much
      evidence points to a role for DNA methylation. The maternal alleles of the
      imprinted H19 gene are active and hypomethylated; the paternal alleles are
      inactive and hypermethylated. Roles for other epigenetic modifications are
      suggested by allele-specific differences in nuclease hypersensitivity at
      particular sites. To further analyze the possible epigenetic mechanisms
      determining monoallelic expression of H19, we have conducted in vivo
      dimethylsulfate and DNase I footprinting of regions upstream of the coding
      sequence in parthenogenetic and androgenetic embryonic stem cells. These cells
      carry only maternally and paternally derived alleles, respectively. We observed
      the presence of maternal-allele-specific dimethylsulfate and DNase I footprints
      at the promoter indicative of protein-DNA interactions at a CCAAT box and at
      binding sites for transcription factors Sp1 and AP-2. Also, at the boundary of a
      region further upstream for which existent differential methylation has been
      suggested to constitute an imprint, we observed a number of strand-specific
      dimethylsulfate reactivity differences specific to the maternal allele, along
      with an unusual chromatin structure in that both strands of maternally derived
      DNA were strongly hypersensitive to DNase I cutting over a distance of 100
      nucleotides. We therefore reveal the existence of novel parent-specific
      epigenetic modifications, which in addition to DNA methylation, could constitute
      imprints or maintain monoallelic expression of H19.

PMID- 9774691
TI  - Involvement of CREB binding protein in expression of major histocompatibility
      complex class II genes via interaction with the class II transactivator.
AB  - The class II transactivator (CIITA) is a key regulatory factor that controls
      expression of the major histocompatibility complex (MHC) class II genes that are
      essential components for antigen presentation and thus regulation of the immune
      response. We show here that the adenovirus E1A protein interferes with the action
      of CIITA and inhibits both B-cell-specific and gamma interferon (IFN-gamma)
      induced expression of MHC class II promoters. Transfection studies provide
      evidence for the functional role of the CREB-binding protein (CBP) in IFN-gamma
      and CIITA-mediated MHC class II promoter activation. We demonstrate that the N
      terminally located transcription activation domain of CIITA physically interacts
      with both the N-terminal and the E1A-binding (C/H3) regions of CBP. These results
      suggest the involvement of a multisubunit complex, which contains the gene
      specific coactivator CIITA and the versatile coactivator CBP, in MHC class II
      gene regulation, which may be responsible for both high-level expression and
      modulation by different signaling pathways.

PMID- 9774692
TI  - The pleckstrin homology and phosphotyrosine binding domains of insulin receptor
      substrate 1 mediate inhibition of apoptosis by insulin.
AB  - Insulin and insulin-like growth factor 1 (IGF-1) evoke diverse biological effects
      through receptor-mediated tyrosine phosphorylation of insulin receptor substrate
      (IRS) proteins. We investigated the elements of IRS-1 signaling that inhibit
      apoptosis of interleukin 3 (IL-3)-deprived 32D myeloid progenitor cells. 32D
      cells have few insulin receptors and no IRS proteins; therefore, insulin failed
      to inhibit apoptosis during IL-3 withdrawal. Insulin stimulated mitogen-activated
      protein kinase in 32D cells expressing insulin receptors (32DIR) but failed to
      activate the phosphatidylinositol 3 (PI 3)-kinase cascade or to inhibit
      apoptosis. By contrast, insulin stimulated the PI 3-kinase cascade, inhibited
      apoptosis, and promoted replication of 32DIR cells expressing IRS-1. As expected,
      insulin did not stimulate PI 3-kinase in 32DIR cells, which expressed a truncated
      IRS-1 protein lacking the tail of tyrosine phosphorylation sites. However, this
      truncated IRS-1 protein, which retained the NH2-terminal pleckstrin homology (PH)
      and phosphotyrosine binding (PTB) domains, mediated phosphorylation of PKB/akt,
      inhibition of apoptosis, and replication of 32DIR cells during insulin
      stimulation. These results suggest that a phosphotyrosine-independent mechanism
      mediated by the PH and PTB domains promoted antiapoptotic and growth actions of
      insulin. Although PI 3-kinase was not activated, its phospholipid products were
      required, since LY294002 inhibited these responses. Without IRS-1, a chimeric
      insulin receptor containing a tail of tyrosine phosphorylation sites derived from
      IRS-1 activated the PI 3-kinase cascade but failed to inhibit apoptosis. Thus,
      phosphotyrosine-independent IRS-1-linked pathways may be critical for survival
      and growth of IL-3-deprived 32D cells during insulin stimulation.

PMID- 9774693
TI  - Direct interaction of Jak1 and v-Abl is required for v-Abl-induced activation of
      STATs and proliferation.
AB  - In Abelson murine leukemia virus (A-MuLV)-transformed cells, members of the Janus
      kinase (Jak) family of non-receptor tyrosine kinases and the signal transducers
      and activators of transcription (STAT) family of signaling proteins are
      constitutively activated. In these cells, the v-Abl oncoprotein and the Jak
      proteins physically associate. To define the molecular mechanism of constitutive
      Jak-STAT signaling in these cells, the functional significance of the v-Abl-Jak
      association was examined. Mapping the Jak1 interaction domain in v-Abl
      demonstrates that amino acids 858 to 1080 within the carboxyl-terminal region of
      v-Abl bind Jak1 through a direct interaction. A mutant of v-Abl lacking this
      region exhibits a significant defect in Jak1 binding in vivo, fails to activate
      Jak1 and STAT proteins, and does not support either the proliferation or the
      survival of BAF/3 cells in the absence of cytokine. Cells expressing this v-Abl
      mutant show extended latency and decreased frequency in generating tumors in nude
      mice. In addition, inducible expression of a kinase-inactive mutant of Jak1
      protein inhibits the ability of v-Abl to activate STATs and to induce cytokine
      independent proliferation, indicating that an active Jak1 is required for these v
      Abl-induced signaling pathways in vivo. We propose that Jak1 is a mediator of v
      Abl-induced STAT activation and v-Abl induced proliferation in BAF/3 cells, and
      may be important for efficient transformation of immature B cells by the v-abl
      oncogene.

PMID- 9774694
TI  - Cse1p is involved in export of yeast importin alpha from the nucleus.
AB  - Proteins bearing a nuclear localization signal (NLS) are targeted to the nucleus
      by the heterodimeric transporter importin. Importin alpha binds to the NLS and to
      importin beta, which carries it through the nuclear pore complex (NPC). Importin
      disassembles in the nucleus, evidently by binding of RanGTP to importin beta. The
      importin subunits are exported separately. We investigated the role of Cse1p, the
      Saccharomyces cerevisiae homologue of human CAS, in nuclear export of Srp1p
      (yeast importin alpha). Cse1p is located predominantly in the nucleus but also is
      present in the cytoplasm and at the NPC. We analyzed the in vivo localization of
      the importin subunits fused to the green fluorescent protein in wild-type and
      cse1-1 mutant cells. Srp1p but not importin beta accumulated in nuclei of cse1-1
      mutants, which are defective in NLS import but not defective in NLS-independent
      import pathways. Purified Cse1p binds with high affinity to Srp1p only in the
      presence of RanGTP. The complex is dissociated by the cytoplasmic RanGTP-binding
      protein Yrb1p. Combined with the in vivo results, this suggests that a complex
      containing Srp1p, Cse1p, and RanGTP is exported from the nucleus and is
      subsequently disassembled in the cytoplasm by Yrb1p. The formation of the
      trimeric Srp1p-Cse1p-RanGTP complex is inhibited by NLS peptides, indicating that
      only NLS-free Srp1p will be exported to the cytoplasm.

PMID- 9774695
TI  - Cytoplasmic dynein intermediate-chain isoforms with different targeting
      properties created by tissue-specific alternative splicing.
AB  - The intermediate chains (ICs) are the subunits of the cytoplasmic dynein that
      provide binding of the complex to cargo organelles through interaction of their N
      termini with dynactin. We present evidence that in Drosophila, the IC subunits
      are represented by at least 10 structural isoforms, created by the alternative
      splicing of transcripts from a unique Cdic gene. The splicing pattern is tissue
      specific. A constitutive set of four IC isoforms is expressed in all tissues
      tested; in addition, tissue-specific isoforms are found in the ovaries and
      nervous tissue. The structural variations between isoforms are limited to the N
      terminus of the IC molecule, where the interaction with dynactin takes place.
      This suggests differences in the dynactin-mediated organelle binding by IC
      isoforms. Accordingly, when transiently expressed in Drosophila Schneider-3
      cells, the IC isoforms differ in their intracellular targeting properties from
      each other. A mechanism is proposed for the regulation of dynein binding to
      organelles through the changes in the content of the IC isoform pool.

PMID- 9774696
TI  - Nuclear mRNA export requires complex formation between Mex67p and Mtr2p at the
      nuclear pores.
AB  - We have identified between Mex67p and Mtr2p a complex which is essential for mRNA
      export. This complex, either isolated from yeast or assembled in Escherichia
      coli, can bind in vitro to RNA through Mex67p. In vivo, Mex67p requires Mtr2p for
      association with the nuclear pores, which can be abolished by mutating either
      MEX67 or MTR2. In all cases, detachment of Mex67p from the pores into the
      cytoplasm correlates with a strong inhibition of mRNA export. At the nuclear
      pores, Nup85p represents one of the targets with which the Mex67p-Mtr2p complex
      interacts. Thus, Mex67p and Mtr2p constitute a novel mRNA export complex which
      can bind to RNA via Mex67p and which interacts with nuclear pores via Mtr2p.

PMID- 9774697
TI  - Schizosaccharomyces pombe retrotransposon Tf2 mobilizes primarily through
      homologous cDNA recombination.
AB  - The Tf2 retrotransposon, found in the fission yeast Schizosaccharomyces pombe, is
      nearly identical to its sister element, Tf1, in its reverse transcriptase-RNase H
      and integrase domains but is very divergent in the gag domain, the protease, the
      5' untranslated region, and the U3 domain of the long terminal repeats. It has
      now been demonstrated that a neo-marked copy of Tf2 overexpressed from a
      heterologous promoter can mobilize into the S. pombe genome and produce true
      transposition events. However, the Tf2-neo mobilization frequency is 10- to 20
      fold lower than that of Tf1-neo, and 70% of the Tf2-neo events are homologous
      recombination events generated independently of a functional Tf2 integrase. Thus,
      the Tf2 element is primarily dependent on homologous recombination with
      preexisting copies of Tf2 for its propagation. Finally, production of Tf2-neo
      proteins and cDNA was also analyzed; surprisingly, Tf2 was found to produce its
      reverse transcriptase as a single species in which it is fused to protease,
      unlike all other retroviruses and retrotransposons.

PMID- 9774698
TI  - Failure of hairpin-ended and nicked DNA To activate DNA-dependent protein kinase:
      implications for V(D)J recombination.
AB  - V(D)J recombination is initiated by a coordinated cleavage reaction that nicks
      DNA at two sites and then forms a hairpin coding end and blunt signal end at each
      site. Following cleavage, the DNA ends are joined by a process that is
      incompletely understood but nevertheless depends on DNA-dependent protein kinase
      (DNA-PK), which consists of Ku and a 460-kDa catalytic subunit (DNA-PKCS or
      p460). Ku directs DNA-PKCS to DNA ends to efficiently activate the kinase. In
      vivo, the mouse SCID mutation in DNA-PKCS disrupts joining of the hairpin coding
      ends but spares joining of the open signal ends. To better understand the
      mechanism of V(D)J recombination, we measured the activation of DNA-PK by the
      three DNA structures formed during the cleavage reaction: open ends, DNA nicks,
      and hairpin ends. Although open DNA ends strongly activated DNA-PK, nicked DNA
      substrates and hairpin-ended DNA did not. Therefore, even though efficient
      processing of hairpin coding ends requires DNA-PKCS, this may occur by activation
      of the kinase bound to the cogenerated open signal end rather than to the hairpin
      end itself.

PMID- 9774699
TI  - Reverse transcription of a self-primed retrotransposon requires an RNA structure
      similar to the U5-IR stem-loop of retroviruses.
AB  - An inverted repeat (IR) within the U5 region of the Rous sarcoma virus (RSV) mRNA
      forms a structure composed of a 7-bp stem and a 5-nucleotide (nt) loop. This U5
      IR structure has been shown to be required for the initiation of reverse
      transcription. The mRNA of Tf1, long terminal repeat-containing retrotransposon
      from fission yeast (Schizosaccharomyces pombe) contains nucleotides with the
      potential to form a U5-IR stem-loop that is strikingly similar to that of RSV.
      The putative U5-IR stem-loop of Tf1 consists of a 7-bp stem and a 25-nt loop.
      Results from mutagenesis studies indicate that the U5-IR stem-loop in the mRNA of
      Tf1 does form and that it is required for Tf1 transposition. Although the loop is
      required for transposition, we were surprised that the specific sequence of the
      nucleotides within the loop was unimportant for function. Additional
      investigation indicates that the loss of transposition activity due to a
      reduction in the loop size to 6 nt could be rescued by increasing the GC content
      of the stem. This result indicates that the large loop in the Tf1 mRNA relative
      to that of the RSV allows the formation of the relatively weak U5-IR stem. The
      levels of Tf1 proteins expressed and the amounts of Tf1 RNA packaged into the
      virus-like particles were not affected by mutations in the U5-IR structure.
      However, all of the mutations in the U5-IR structure that caused defects in
      transposition produced low amounts of reverse transcripts. A unique feature in
      the initiation of Tf1 reverse transcription is that, instead of a tRNA, the first
      11 nt of the Tf1 mRNA serve as the minus-strand primer. Analysis of the 5' end of
      Tf1 mRNA revealed that the mutations in the U5-IR stem-loop that resulted in
      defects in reverse transcription caused a reduction in the cleavage activity
      required to generate the Tf1 primer. Our results indicate that the U5-IR stems of
      Tf1 and RSV are conserved in size, position, and function.

PMID- 9774701
TI  - Glucosamine-6-phosphate deaminase from beef kidney is an allosteric system of the
      V-type.
AB  - The enzyme glucosamine-6-phosphate deaminase from beef kidney has been purified
      to homogeneity by allosteric-site affinity chromatography. Its amino acid
      composition and the N-terminal sequence (1-42), were obtained. The amino acid
      sequence of this segment is essentially identical to the corresponding regions of
      the human and hamster glucosamine-6-phosphate deaminases. The beef enzyme is a
      hexamer of 32.5 kDa subunits; this is nearly 2.5 kDa higher than the molecular
      mass of the homologous enzyme from Escherichia coli. Beef kidney deaminase
      exhibits a notable difference from the bacterial enzyme in its allosteric
      activation by N-acetylglucosamine 6-phosphate This metabolite, which is also is
      the allosteric activator of the bacterial glucosamine-6-phosphate deaminase,
      activates the enzyme by increasing its kcat without any change in the Km values
      for glucosamine 6-phosphate, over a wide range of activator concentration. This
      observation places beef kidney deaminase in the class of V-type allosteric
      systems.

PMID- 9774700
TI  - Exploring functional redundancy in the immunoglobulin mu heavy-chain gene
      enhancer.
AB  - Immunoglobulin (Ig) mu heavy-chain gene enhancer activity is mediated by multiple
      DNA binding proteins. Mutations of several protein binding sites in the enhancer
      do not affect enhancer activity significantly. This feature, termed redundancy,
      is thought to be due to functional compensation of the mutated sites by other
      elements within the enhancer. In this study, we identified the elements that make
      the basic helix-loop-helix (bHLH) protein binding sites, muE2 and muE3,
      redundant. The major compensatory element is a binding site for interferon
      regulatory factors (IRFs) and not one of several other bHLH protein binding
      sites. These studies also provide the first evidence for a role of IRF proteins
      in Ig heavy-chain gene expression. In addition, we reconstituted the activity of
      a monomeric mu enhancer in nonlymphoid cells and defined the domains of the ETS
      gene required for function.

PMID- 9774702
TI  - The human pancreatic alpha-amylase isoforms: isolation, structural studies and
      kinetics of inhibition by acarbose.
AB  - A rapid method is proposed for isolating the two main components of human
      pancreatic alpha-amylase (HPA I and HPA II). The isoelectric point of HPA I
      (7.2), the main component, was determined using an isoelectrofocusing method and
      found to differ from that of HPA II (6. 6). The molecular mass of HPA I (55862+/
      5 Da) and that of HPA II (55786+/-5 Da) were determined by performing mass
      spectrometry and found to be quite similar to that of the protein moiety
      calculated from the amino acid sequence (55788 Da), which indicates that the
      human amylase is not glycosylated. The structure of both HPA I and HPA II was
      further investigated by performing limited proteolysis. Two fragments with an
      apparent molecular mass of 41 kDa and 14 kDa were obtained by digesting the
      isoforms with proteinase K and subtilisin, whereas digestion with papain yielded
      two cleaved fragments with molecular masses of 38 kDa and 17 kDa. Proteinase K
      and subtilisin susceptible bonds are located in the L8 loop (A domain), while the
      papain cut which occurs in the presence of the calcium chelator EDTA is in the L3
      loop (B domain). The kinetics of the inhibition of HPA I and HPA II by acarbose,
      a drug used to treat diabetes and obesity, were studied using an amylose
      substrate. The Lineweaver-Burk primary plots of HPA I and HPA II, which did not
      differ significantly, indicated that the inhibition was of the mixed non
      competitive type. The secondary plots gave parabolic curves. All in all, these
      data provide evidence that two acarbose molecules bind to HPA. In conclusion,
      apart from the pI, no significant differences were observed between HPA I and HPA
      II as regards either their molecular mass and limited proteolysis or their
      kinetic behavior. As was to be expected in view of the high degree of structural
      identity previously found to exist between human and porcine pancreatic amylases,
      the present data show that the inhibitory effects of acarbose on the kinetic
      behavior of these two amylases are quite comparable. In particular, the process
      of amylose hydrolysis catalyzed by HPA as well as by PPA in both cases requires
      two carbohydrate binding sites in addition to the catalytic site.

PMID- 9774703
TI  - Glycosylation and NH2-terminal domain mutants of the tissue inhibitor of
      metalloproteinases-1 (TIMP-1).
AB  - Mutants in the tissue inhibitor of metalloproteinases-1 (TIMP-1) protein have
      been created by site-directed mutagenesis and expressed in HeLa cells, using a
      recombinant vaccinia virus system. Removal of either or both glycosylation sites
      yielded proteins which retained wild-type inhibitory activity against both human
      fibroblast-type collagenase (FIB-CL) and Mr 72000 gelatinase (GL). However, the
      double glycosylation mutant protein was expressed at a level that was 2-4-fold
      lower than that of the wild-type or the single site glycosylation mutants. The
      'tiny-TIMP' COOH-terminal deletion mutant that lacks the last 57 residues was
      also inhibitory, but the dose-response curve suggested that the interaction with
      the Mr 72000 gelatinase had been altered. A number of replacement mutants in the
      highly conserved NH2-terminal domain, including replacement of P5A and P8A or a
      double mutation in the VIRAK sequence which is absolutely conserved in all TIMPs
      in all species (VIRAK to VIAAA), also yielded functional proteins capable of
      inhibiting FIB-CL and Mr 72000 GL and of forming SDS-resistant complexes with FIB
      CL. None of the above manipulations abolished inhibitory function suggesting that
      binding of the inhibitor by the enzyme involves multiple interactions.

PMID- 9774704
TI  - Photoaffinity labelling of the human mineralocorticoid receptor with steroids
      having a reactive group at position 3, 18 or 21.
AB  - The ability of a glucocorticoid (triamcinolone acetonide: TA) and three
      progesterone derivatives with photoreactive groups at different positions
      (promegestone: R5020; 18-oxo-18-vinylprogesterone: 18OVP; 21-diazoprogesterone:
      21DP) to bind covalently to the human mineralocorticoid receptor (hMR) expressed
      in Sf9 insect cells was assessed. Sedimentation gradient analysis and exchange
      assays with aldosterone showed that [3H]TA, a partial mineralocorticoid agonist,
      and [3H]R5020, a pure antimineralocorticoid, were covalently bound to hMR after
      UV irradiation, with a labelling efficiency of approx. 3-5%. UV irradiation did
      not alter the heterooligomeric structure of the hMR, since the irradiated [3H]TA-
      and [3H]R5020-hMR complexes sedimented at approx. 9-10 S, as did the non
      irradiated complexes. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis
      revealed a band labelled by [3H]TA or [3H]R5020, having a molecular mass of 120
      kDa. This band was not detected in the presence of an excess of the corresponding
      unlabelled steroid or when the cytosol was recovered from non-infected Sf9 cells.
      Electrophoresis of a truncated hMR (hMRDelta(1-351)) photolabelled with [3H]TA
      revealed a 80 kDa band, compatible with the molecular mass of the truncated hMR.
      Limited chymotrypsin proteolysis of the [3H]TA photolabelled hMR generated a 30
      kDa fragment covalently associated with [3H]TA. As the 30 kDa fragment generated
      by chymotrypsin has been shown to encompass the entire ligand-binding domain of
      the hMR (B. Couette, J. Fagart, S. Jalaguier, M. Lombes, A. Souque, M.E. Rafestin
      Oblin, Biochem. J. 315 (1996) 421-427), the present experiments provide evidence
      that [3H]TA is covalently bound to the ligand binding domain of the hMR. Exchange
      assays with [3H]A also revealed that unlabelled 18OVP and 21DP, two
      mineralocorticoid agonists bearing photoreactive groups at skeleton positions
      crucial for the ligand-MR interaction, are covalently bound to hMR with an
      approx. 30-35% labelling efficiency.

PMID- 9774705
TI  - Improved conditions for the removal of 2-oxoacyl groups from the N-terminus of
      proteins.
AB  - Proteins with R-CO-CO-NH- at the N-terminus, rather than the usual R-CH(-NH3+)-CO
      NH-, are produced by non-enzymic transamination and also occur in the pyruvoyl
      enzymes. The oxoacyl group may be specifically removed from a model peptide, in
      yields of 70-80%, by treating them in 0.1 M phosphate buffer at 37 degreesC for
      24 h with 25 mM of the N-phosphonomethyl derivative of phenylene-1,2-diamine.
      This provides mild conditions for the stepwise removal of N-terminal residues
      without denaturation.

PMID- 9774706
TI  - Substrate binding subsites of chitinase from barley seeds and lysozyme from goose
      egg white.
AB  - Substrate binding subsites of barley chitinase and goose egg white lysozyme were
      comparatively investigated by kinetic analysis using N-acetylglucosamine
      oligosaccharide as the substrate. The enzymatic hydrolysis of hexasaccharide was
      monitored by HPLC, and the reaction time-course was analyzed by the mathematical
      model, in which six binding subsites (B, C, D, E, F, and G) and bond cleavage
      between sites D and E are postulated. In this model, all of the possible binding
      modes of substrate and products are taken into consideration assuming a rapid
      equilibrium in the oligosaccharide binding processes. To estimate the binding
      free energy changes of the subsites, time-course calculation was repeated with
      changing the free energy values of individual subsites, until the calculated time
      course was sufficiently fitted to the experimental one. The binding free energy
      changes of the six binding subsites, B, C, D, E, F and G, which could give a
      calculated time-course best fitted to the experimental, were 0.0, -5.0, +4.1, 
      0.5, -3.8, and -2.0 kcal/mol for barley chitinase, and -0.5, -2.2, +4.2, -1.5, 
      2.6, and -2.8 kcal/mol for goose egg white lysozyme. The binding mode predicted
      from the p-nitrophenyl-penta-N-acetylchitopentaoside splitting pattern for each
      enzyme was also analyzed by the identical subsite model. Using the free energy
      values listed above, the binding mode distribution calculated was fitted to the
      experimental with a slight modification of free energy value at site G. We
      concluded that the binding subsite model described above reflects the substantial
      mechanism of substrate binding for both enzymes. The relatively large disparity
      in free energy value at site C between these enzymes may be due to the different
      secondary structures of polypeptide segments interacting with the sugar residue
      at site C.

PMID- 9774707
TI  - Proton resonance assignments and ligand exchange kinetics in high-spin and mixed
      spin myoglobin complexes using two-dimensional exchange spectroscopy.
AB  - The task of assigning resonances in proton nuclear magnetic resonance spectra of
      paramagnetic heme proteins can be an arduous process, but with the development of
      multi-dimensional NMR methods the situation has improved. It is demonstrated here
      that two-dimensional exchange spectroscopic experiments can be used to obtain to
      assignment correlations for the heme protons of methydroxy-, metthiocyano-,
      metaquo-, and metimidazole-myoglobin forms. All the assignments are unambiguous
      and straightforward when the temperature and mixing times are adjusted to
      minimize nuclear Overhauser cross-peaks from each complex. Moreover, saturation
      transfer experiments allow the study of ligand binding kinetics. The exchange
      rates between metaquo- and metimidazole- (or methyl substituted imidazole)
      myoglobin complexes are estimated. The differences between the exchange rates
      reflect differences in the hydrophobic and steric interactions between the
      ligands and the protein moiety.

PMID- 9774708
TI  - Unique primary structure of a thermostable multimetal beta-galactosidase from
      Saccharopolyspora rectivirgula.
AB  - The gene of the monomeric multimetal beta-galactosidase of Saccharopolyspora
      rectivirgula was cloned and sequenced. Although the enzyme could be assigned as a
      member of beta-galactosidases belonging to the glycosyl hydrolase family 2, it
      has unusual structural features for beta-galactosidase of this family; it
      contained a unique sequence which consists of approximately 200 amino acid
      residues with no similarity to known proteins. This 200-residue sequence exists
      as if it is inserted into a sequence homologous to the active-site domain of the
      Escherichia coli lacZ enzyme.

PMID- 9774709
TI  - The inactivation kinetics of papain by guanidine hydrochloride: a re-analysis.
AB  - The kinetic theory of the substrate reaction during modification of enzyme
      activity has been applied to study the inactivation kinetics of enzymes by
      denaturant. However, an important problem related to the determination of the
      inactivation rate constants has not been considered in a previous publication
      (Xiao, et al., Biochim. Biophys. Acta, 1164 (1993) 54-60). In most denaturation
      experiments, the high concentrations of denaturants may greatly affect the
      kinetic behavior of the system to preclude the use of the kinetic parameters
      determined in the absence of denaturant. In the present study, the kinetic
      equation of substrate reaction in presence of denaturant has been derived. A re
      examination of the effect of high concentrations of guanidine hydrochloride on
      the inactivation of papain, taking into consideration the effect of high
      concentrations of guanidine hydrochloride on the Michaelis constant, showed that,
      for papain, the substrate gives no protection on its inactivation. It is the
      purpose of the present communication to stress the importance of observing the
      effect of the denaturant on the kinetic parameters for kinetic analysis of enzyme
      inactivation by denaturants generally.

PMID- 9774710
TI  - Thermodynamics of ligand (substrate/end product) binding to endoxylanase from
      Chainia sp. (NCL-82-5-1): isothermal calorimetry and fluorescence titration
      studies.
AB  - The binding of xylo-oligosaccharides to Chainia endoxylanase resulted in a
      decrease in fluorescence intensity of the enzyme with the formation of 1:1
      complex. Equilibrium and thermodynamic parameters of ligand binding were
      determined by fluorescence titrations and titration calorimetry. The affinity of
      xylanase for the oligosaccharides increases in the order X2<X3<X4</=X5.
      Contributions from the enthalpy towards the free energy change decreased with
      increasing chain length from X2 to X4, whereas an increase in entropy was
      observed, the change in enthalpy and entropy of binding being compensatory. The
      entropically driven binding process suggested that hydrophobic interactions as
      well as hydrogen bonds play a predominant role in ligand binding.

PMID- 9774711
TI  - Role of the primary auditory cortex in auditory selective attention studied by
      whole-head neuromagnetometer.
AB  - In order to identify the human cortical areas involved in the auditory attention,
      neuromagnetic fields were recorded from 12 healthy adults with a 122-channel
      whole-head magnetometer while the subjects performed the auditory selective
      attention task. Randomized sequence of 900 Hz (P=0.9) and 950 Hz (P=0.1) tones
      was presented to each ear with random interstimulus intervals across ears ranging
      from 300 to 500 ms. Subjects were asked to pay attention to the designated ear
      (attended ear) and to count the number of the 950 Hz tones presented to the
      attended ear. Twelve sessions were performed for each subject, among which the
      attended ear was changed alternately in a counterbalanced order among subjects.
      In seven out of twelve subjects, averaged neuromagnetic fields in response to
      frequent tones presented to the attended ear showed attention-related deflection
      over the bilateral temporal areas starting at around 100 ms after the stimulus
      presentation. Although the dipole moment for N100m in the attended condition
      showed significant increase compared to that in the non-attended condition,
      locations of the two equivalent current dipoles in the auditory cortex were not
      significantly different from each other. Moreover, a simulation study supported
      the enhancement of N100m rather than participation of additional dipoles in the
      auditory selective attention task. These results suggest that the primary
      auditory cortex plays a main role in the auditory selective attention starting as
      early as 100 ms after the stimulus presentation.

PMID- 9774712
TI  - beta-Microseminoprotein/prostatic secretory protein is a member of immunoglobulin
      binding factor family.
AB  - Human seminal plasma contains a factor that binds human IgG, designated as
      immunoglobulin binding factor (IgBF). Under reducing condition IgBF interacts
      with anti-Leu-11b, a murine monoclonal antibody raised against human
      FcgammaRIII/CD16. IgBF shows no binding activity under non-reducing condition.
      Three components having IgBF activity were separated by HPLC and their amino acid
      sequences determined. The main IgBF showed structural identity to beta
      microseminoprotein (beta-MSP), prostatic secretory protein of 94 amino acids
      (PSP94) and beta-inhibin. The slight variation in the reported sequences of these
      proteins has been attributed to analytical error. In the present study the
      molecular masses of main IgBF and beta-MSP/PSP94 were found to be identical by
      mass spectrometry. In addition, a large component of IgBF and a shorter beta-MSP
      consisting of 93 amino acids were identified. The binding of beta-MSP for human
      IgG and anti-Leu-11b antibody is demonstrable only under reducing condition,
      determined by Western blot analysis. The present data clearly show that IgBF is a
      family composed of at least three isoforms. One of the members is beta-MSP/PSP94.
      This family should be designated as IgBF.

PMID- 9774713
TI  - Solution structure of a fragment of the dimerization domain of E2F-1 determined
      by circular dichroism, 1H nuclear magnetic resonance and distance geometry.
AB  - The structure of a synthesized peptide with the sequence
      GVVDLNWAAEVLKVQKRRIYDITNVLEGIQ which corresponds to residues 149-178 of
      transcription factor E2F-1 was determined by 1H nuclear magnetic resonance in 40%
      d3-TFE/water. NOE cross peaks and alphaH chemical shifts indicate that the
      peptide consists of a helix from Ala-8 to Leu-26 in this solution. Circular
      dichroism measurements confirm the presence of nearly 45% helix in TFE/water
      solution but show no evidence of helicity in water solution of this peptide.
      Fifty structures were constructed with 329 upper distance limits by DIANA. The 20
      best conformers show a RMSD of 0.78 A for backbone atoms and 1.78 A for heavy
      atoms from residue Ala-8 to Leu-26. This result, together with our previous work
      on the solution structure of a fragment of DP-1, supports the proposal that E2F-1
      and DP-1 may dimerize with a coiled-coil type interaction.

PMID- 9774715
TI  - A spatio-temporal comparison of semantic and episodic cued recall and recognition
      using event-related brain potentials.
AB  - The event-related brain potential (ERP) was used to spatially and temporally map
      the brain areas active as a function of type of recall (semantic vs. episodic)
      and episodic retrieval mode (recall vs. recognition) while difficulty of episodic
      recall was manipulated. ERPs were recorded from 32 scalp sites in 12 subjects,
      along with behavioral accuracy and recall speed. The results revealed that
      different but overlapping patterns of ERP activity were elicited during semantic
      and episodic recall. Recall of both types of information was characterized by ERP
      activity over left inferior frontal, central, bilateral temporal and posterior
      inferior brain areas. Compared to semantic recall, episodic recall elicited more
      activity over the frontal poles and right frontal scalp. Different but
      overlapping patterns of ERP activity were also found as a function of episodic
      retrieval mode. While episodic recall and recognition showed similar activity
      over the frontal poles and central scalp, there was no left inferior frontal
      activity elicited during recognition and no large, topographically widespread,
      late positive component (LPC) elicited when the same words were recalled.
      Manipulation of episodic recall difficulty and analysis of trials when recall
      failed indicated that these task (i.e., episodic vs. semantic) and retrieval mode
      (recall vs. recognition) differences in ERP activity were not likely to be due to
      differences in task difficulty. The results are discussed in terms of processes
      that the ERP activity may reflect and their similarity to results of PET studies
      of semantic and episodic retrieval.

PMID- 9774714
TI  - Cortical regions involved in visual texture perception: a fMRI study.
AB  - To determine visual areas of the human brain involved in elementary form
      processing, functional magnetic resonance imaging (fMRI) was used to measure
      regional responses to two types of achromatic textures. Healthy young adults were
      presented with 'random' textures which lacked spatial organization of the black
      and white pixels that make up the image, and 'correlated' textures in which the
      pixels were ordered to produce extended contours and rectangular blocks at
      multiple spatial scales. Relative to a fixation condition, random texture
      stimulation resulted in increased signal intensity primarily in the striate
      cortex, with slight involvement of the cuneus and middle occipital, lingual and
      fusiform gyri. Correlated texture stimulation also resulted in activation of
      these areas, yet the regional extent of this activation was significantly greater
      than that produced by random textures. Unlike random stimulation, correlated
      stimulation additionally resulted in middle temporal activation. Direct
      comparison of the two stimulation conditions revealed significant differences
      most consistently in the anterior fusiform gyrus, but also in striate, middle
      occipital, lingual and posterior temporal regions in subjects with robust
      activation patterns. While both random and correlated stimulation produced
      activation in similar areas of the occipital lobe, the increase in regional
      activation during the correlated condition suggests increased recruitment of
      neuronal populations occurs in response to textures containing visually salient
      features. This increased recruitment occurs within striate, extrastriate and
      temporal regions of the brain, also suggesting the presence of receptive field
      mechanisms in the ventral visual pathway that are sensitive to features produced
      by higher-order spatial correlations.

PMID- 9774716
TI  - Thiol/disulfide exchange between small heat shock protein 25 and glutathione.
AB  - Murine small heat shock protein 25 (Hsp25) carries a single Cys-residue at
      position 141 of its amino acid sequence. In glutathione redox buffers, Hsp25
      equilibrates between reduced protein (PSH), mixed disulfide (PSSG) and protein
      dimer (PSSP) forms. At highly oxidative conditions, native Hsp25 predominantly
      forms PSSP while denatured Hsp25 forms PSSG. Conversion of PSSP to PSSG
      correlates with urea and temperature denaturation of tertiary and/or quaternary
      structure of Hsp25. At pH 7.5, 25 degreesC, the second-order rate constant for
      the formation of PSSP in the reaction of native PSH with GSSG is 20.1+/-1.4 M-1
      min-1. This is approximately 3-fold lower than the reaction velocity of GSSG with
      a typical, unhindered thiol of pKa 8.6. At redox equilibrium, the fractions of
      PSSP, PSSG, and PSH depend on the concentration of GSH and less on the ratio
      [GSH]/[GSSG] (R). At a constant R, the fractions of PSSG and PSH species depend
      similarly on GSH concentration, being approximately equal in glutathione redox
      buffers with low R. It is concluded that in oligomeric complexes, Hsp25 subunits
      in vitro form stable dimers, in which the reacting -SH groups are in a proximity
      to form intersubunit disulfide bonds. Within a reaction of one of these -SH
      groups with GSSG, steric hindrances and electrostatic repulsion complicate
      penetration of another reduced or oxidized glutathione molecule to the reaction
      site.

PMID- 9774717
TI  - Self-association of 8-anilino-1-naphthalene-sulfonate molecules: spectroscopic
      characterization and application to the investigation of protein folding.
AB  - It was suggested long ago that the reason for the considerable increase of 8
      anilino-1-naphthalene-sulfonate (8-ANS) fluorescence intensity upon the
      transition from aqueous to organic solvents is the dissociation of 8-ANS
      associates. To clarify this point the dependence of spectral properties of the
      dye on concentration and solvent composition was investigated by means of steady
      state and time-resolved fluorescence spectroscopy. It was shown that the increase
      of 8-ANS concentration leads to the changes in the shape of absorption and
      fluorescence spectra of the dye, accompanied by the decrease in its fluorescence
      decay time values. Such changes were observed in aqueous and organic solvents for
      Mg2+- and NH+4-salts of 8-anilino-1-naphthalene-sulfonateic acid and reflect the
      existence of self-association of the dye molecules in both media. However, the
      decrease in fluorescence intensity induced by the self-association of the probe
      molecules is too small to explain weak fluorescence of 8-ANS in water. At the
      same time, it expounds the difference between the decay times of protein-embedded
      8-ANS molecules upon interaction of this probe with native and molten globule
      proteins.

PMID- 9774718
TI  - Changes of somatosensory evoked potentials preceding rapid voluntary movement in
      Go/No-go choice reaction time task.
AB  - To elucidate the sensorimotor mechanisms in preparation of voluntary movement, we
      examined the changes of the somatosensory evoked potentials (SEPs) following
      median nerve stimulation in Go/No-go choice-reaction time task. Eleven normal
      subjects performed extension of the middle finger according to the Go signal
      while they did not make any movement and relaxed on the No-go and Control
      signals, respectively. Each signal was randomly presented on a computer screen in
      front of the subject. Single pulse stimulation was applied to the right median
      nerve at 150 ms after the response signal in each Go/No-go and Control sequence
      so as to be just before the voluntary movement in the Go sequence. The SEPs were
      recorded from F3, C3' (midpoint between P3 and C3) and P3 on the left hemisphere.
      In comparison with the Control sequence, the amplitude of N20 and P25 recorded
      from C3' and P3 was significantly attenuated before movement in the Go sequence
      (P<0.02, ANOVA with Bonferroni-Dunn post hoc procedure). On the other hand, the
      parietal N33 and frontal N30 were attenuated in both Go and No-go sequences
      (P<0.02). None of the SEP components were changed when the stimulus was delivered
      before the response signal. We speculate that the attenuation of N20 was linked
      with the activation of the motor cortex followed by the actual movement. The
      attenuation of other components up to 33 ms after stimulus were considered to be
      more related to the preparation or the attention to the voluntary movement than
      to the movement itself.

PMID- 9774719
TI  - Effects of prefrontal lesions on lexical processing and repetition priming: an
      ERP study.
AB  - The role of left prefrontal cortex in lexical-semantic processing remains a
      matter of some debate. Functional neuroimaging experiments have reported blood
      flow changes in left inferior prefrontal cortex (LIPC) during tasks that involve
      word retrieval and semantic processing. Some of these studies have also
      implicated LIPC in repetition priming. To determine the necessity of prefrontal
      cortex for these types of memory and to elucidate their time-course, behavioral
      and event-related potential (ERP) correlates of lexical processing and repetition
      priming were examined in 11 stroke patients with lesions centered in dorsolateral
      prefrontal cortex (areas 9 and 46). Damage extended inferiorly and posteriorly to
      areas 6, 8, 44, and 45 in some subjects, so patients were subdivided into
      anterior and posterior frontal subgroups. Visually presented words and
      pronounceable non-words were repeated after one of three delays. Subjects
      categorized stimuli as either words or non-words in a lexical decision task.
      Controls showed significant word priming at all three delays. Old words elicited
      more positive-going potentials than new words, beginning at 300 ms and lasting
      until 500-700 ms. This ERP repetition effect was reduced, but not eliminated, by
      both anterior and posterior frontal lesions. However, behavioral priming was
      intact in the patients, suggesting that prefrontal cortex may modulate the neural
      generators in posterior cortical regions that are critical for priming. Left
      posterior frontal lesions resulted in impaired performance in the lexical
      decision task and a reduction in the amplitude of the late positive component
      (LPC). These latter findings suggest that left posterior prefrontal cortex is
      important for the categorization and selection processes required by lexical
      semantic tasks.

PMID- 9774720
TI  - Picosecond tryptophan fluorescence of membrane-bound prothrombin fragment 1.
AB  - The wavelength-dependent tryptophan (Trp) fluorescence decays of Ca-prothrombin
      fragment 1 (Ca-BF1), which contains three tryptophan residues, in the presence of
      pure phosphatidylcholine (PC) small unilamellar vesicles (SUV) and PC-SUV
      containing either 25% phosphatidyl-l-serine (PS), and 25% or 40%
      phosphatidylglycerol (PG) are characterized, using fluorescence lifetime
      distribution, conventional multiexponential, and global analysis. In analogy to
      previous investigations on apo- and Ca-BF1 (M. Hof, G.R. Fleming, V. Fidler,
      Proteins Struct. Func. Genet. 24 (1996) 485-494), the analysis resulted in a five
      exponential decay model in all investigated systems, where the five fluorescence
      lifetimes (e.g. 0. 04+/-0.02 ns (component A), 0.24+/-0.02 ns (B), 0.66+/-0.03 ns
      (C), 2.4+/-0.3 ns (D), and 5.4+/-0.4 ns (E) for Ca-BF1 in the presence of PC-SUV)
      are wavelength-independent. The fluorescence lifetimes and the corresponding
      amplitudes of the 'Gla-Trp' (components D and E) and of the two 'kringle-Trp'
      (components B, C, and D) remain unchanged when bound to the PS-containing
      vesicles. Saturation binding to PG-containing membranes leads to a prolongation
      of the Gla component E from 5.3 in solution to 7.5 ns, indicating a change in the
      Gla-domain conformation. The results represent the first experimental evidence of
      a lipid-specific conformational change in the N-terminal 'Gla domain' of a
      vitamin K-dependent protein.

PMID- 9774721
TI  - A novel microtubule independent effect of paclitaxel: the inhibition of
      peptidylarginine deiminase from bovine brain.
AB  - Although the principal effect of paclitaxel (taxol) is in preventing
      depolymerization of microtubules, other effects have been described recently. In
      the present manuscript, we demonstrate an inhibitory effect on the enzyme
      peptidylarginine deiminase (PAD) which converts peptidyl bound arginine to
      citrulline. To study the mechanism of action of the drug on PAD, a number of
      studies were carried out with purified enzyme. With the synthetic substrate
      benzoyl-arginine ethyl ester (BAEE), almost total inhibition of activity was
      observed at 12. 5 mM. With myelin basic protein (MBP) as a substrate, deimination
      of arginyl residues was prevented by 0.5 mM paclitaxel. The velocity-substrate
      curve was unusual since substrate enhancement was observed at 5 mM BAEE. These
      data suggested the presence of two binding sites on the enzyme. Inhibition of
      activity by paclitaxel was non-competitive for both sites.

PMID- 9774722
TI  - Modulation of human auditory information processing by emotional visual stimuli.
AB  - Auditory event-related potentials mismatch negativity (MMN) and N100 were
      recorded from seven subjects while they read text and watched emotionally
      negative, neutral, and positive pictures varying in valence and arousal. The MMN
      reflects automatic detection of change in auditory stimulus stream. Functionally
      different N100 is triggered by onset of various auditory stimuli. The N100 was
      stabile during all visual conditions. The MMN was very similar during text
      reading, and neutral and negative slide viewing, but was significantly attenuated
      during viewing of positively valenced slides. We suggest that visual emotional
      information of high positive valence and low arousal is a signal of
      nonthreatening and nonappetitive environment. This kind of environment probably
      reduces the need for auditory change detection.

PMID- 9774723
TI  - Enantiomeric inhibitors of cholesterol esterase and acetylcholinesterase.
AB  - Enantiomers of N-methyl-N,alpha-methylbenzylbutyramide (1), 1-butyl-3-methyl-3'
      alpha-methylbenzylurea (2), 1,2,3, 4-tetrahydro-1-naphthyl-N-butylcarbamate (3),
      1,1'-bi-2-naphthyl-2, 2'-di-N-butylcarbamate (4), 1, 1'-bi-2-naphthyl-2-ol-2'-N
      butylcarbamate (5), and 1, 1'-bi-2-naphthyl-2-butyrate-2'-N-butylcarbamate (6)
      are inhibitors of porcine pancreatic cholesterol esterase-catalyzed hydrolysis of
      4-nitrophenyl butyrate and of electric eel acetylcholinesterase-catalyzed
      hydrolysis of acetylthiocholine in the presence of 5,5'-dithiobis-2
      nitrobenzoate. For competitive inhibitors, values of the inhibition constant (Ki)
      and the enantiomeric ratio (Ecomp.) are investigated. For active site-directed
      irreversible inhibitors, values of the inhibition constant (Ki), the
      carbamylation constant (k2), the bimolecular rate constant (ki), and the
      enantiomeric ratio (E) are investigated. Toward both enzymes, compounds 1 are
      poor competitive inhibitors (Ki=102-104 microM) but have good
      enantioselectivities (Ecomp.=10-50, the preference for R). R-2 and S-2 are
      competitive inhibitors of acetylcholinesterase with Ki=26 and 80 microM,
      respectively (the preference for R) but are active site-directed irreversible
      inhibitors of cholesterol esterase with ki=4 and 16 M-1 sec-1, respectively (the
      preference for S). For those competitive inhibitions, both leaving group
      hydrophilic and hydrophobic binding sites of cholesterol esterase or both anionic
      substrate binding site and peripheral anionic binding site of
      acetylcholinesterase bind to N,N-methyl-alpha-methylbenzyl disubstituted amide
      parts of these inhibitors and the enzyme does not catalyze the hydrolysis of
      these inhibitors. The opposite stereopreference (S) for the inhibition of
      cholesterol esterase by compounds 2 may be due to the fact that N, N-methyl-alpha
      methylbenzyl disubstituted amide parts of these inhibitors bind to the alkyl
      chain binding site of the enzyme. Compounds 3-6 are active site-directed
      irreversible inhibitors of cholesterol esterase (ki=1-13000 M-1 s-1) and
      peripheral anionic binding site-directed irreversible inhibitors of
      acetylcholinesterase (ki=1.7-1300 M-1 s-1). Compounds 3 have low
      enantioselectivities (E=1.3-1.4) for both enzymes. The stereopreference for
      atropisomers 4 and 6 is S-form toward both enzymes (E=2-30) and is identical to
      that of cholesterol esterase-catalyzed hydrolysis of 1,1'-bi-2-naphthyl-2,2'
      diacylate. This stereopreference (S) may be due to the fact that the butyryl
      group or one of two butylcarbamate groups of S-atropisomers binds more
      effectively to the leaving group hydrophobic binding site of cholesterol esterase
      or the peripheral anionic binding site of acetylcholinesterase than that of R
      atropisomers. The opposite stereopreference (R) for atropisomers 5 toward both
      enzymes may be due to a favorable interaction between the hydroxyl group of the
      inhibitors and the leaving group hydrophilic binding site of cholesterol esterase
      or the peripheral anionic binding site of acetylcholinesterase.

PMID- 9774724
TI  - Somatosensory automatic responses to deviant stimuli.
AB  - We studied event-related potentials (ERPs) produced in response to deviant
      stimuli in a sequence of somatosensory stimuli which were measured under stimulus
      ignoring conditions. A change in the repetitive somatosensory input elicited not
      only a frontal negativity which was similar to the somatosensory mismatch
      negativity very recently reported by Kekoni et al. [J. Kekoni, H. Hamalainen, M.
      Saarinen, J. Grohn, K. Reinikainen, A. Lehtokoski, R. Naatanen, Rate effect and
      mismatch responses in the somatosensory system: ERP-recordings in humans, Biol.
      Psychol. 46 (1997) 125-142] but also a positive deflection ranging in latency
      from 100 to 200 ms. This somatosensory change-related positivity was reduced with
      prolongation of the interstimulus interval (ISI) and was different from the
      responses to the deviant stimuli when they were presented alone. These findings
      suggest that the somatosensory change-related positivity is probably generated
      not by activation of new afferent elements but by a detection of change in a
      process of comparison with sensory memory.

PMID- 9774725
TI  - Scanning direction and line bisection: a study of normal subjects and unilateral
      neglect patients with opposite reading habits.
AB  - Sixty normal dextrals (30 left-to-right and 30 right-to-left readers) and two
      left unilateral neglect patient with opposite reading habits performed a passive
      line bisection task. In order to study the effect of scanning direction on
      performance, subjects had to stop a mark moving on the to-be-bisected line either
      from the left to the right or in the opposite direction. Results showed that the
      position of the subjective middle was dependent upon the scanning direction of
      the line for all the subjects. A leftward deviation appeared for left to right
      scanning, whereas a rightward shift occurred when the mark moved from the right
      to the left. These results emphasize the role of scanning direction in space
      organization and are discussed with respect to the explanatory hypotheses of
      unilateral neglect.

PMID- 9774726
TI  - Inhibition of camel lens zeta-crystallin/NADPH:quinone oxidoreductase by
      pyridoxal-5'-phosphate.
AB  - Camel lens zeta-crystallin was inhibited by pyridoxal-5'-phosphate (PAL-P) and o
      phthalaldehyde. PAL-P inactivated zeta-crystallin in a time- and concentration
      dependent manner. The initial rate of inactivation followed pseudo-first-order
      kinetics with the second-order rate constant of 91 M-1 s-1. The modified enzyme
      showed the characteristic absorption peak at 325 nm indicative of the formation
      of phosphopyridoxallysine. Quantitative analysis suggested the incorporation of 1
      mole of PAL-P/subunit of enzyme. NADPH was able to substantially protect zeta
      crystallin against PAL-P inactivation, whereas the substrate 9,10
      phenanthrenequinone (PQ) did not provide any protection. Inhibition of zeta
      crystallin by PAL-P was uncompetitive with NADPH (Ki=37 microM) and non
      competitive with respect to the substrate (Ki=57 microM). Inhibition of zeta
      crystallin by o-phthalaldehyde was used to establish the location of an essential
      lysine residue. Incubation of zeta-crystallin with o-phthalaldehyde resulted in
      the formation of an isoindole derivative that had a characteristic fluorescence
      spectrum. This suggested that a lysine residue is located within 3 A of a
      cysteine residue at the NADPH binding region. SDS-PAGE showed the o
      phthalaldehyde-modified enzyme remained largely monomer (approx. 80%), although
      bands corresponding to dimer and tetramer forms were also present. These results
      suggested that an essential lysine residue is located in the vicinity of the
      NADPH binding site. This residue may simply ensure the proper binding of NADPH to
      the active site of zeta-crystallin.

PMID- 9774727
TI  - Event-related potentials during digit recognition tasks.
AB  - OBJECTIVE: An event-related potential (ERP) correlate of visual short-term memory
      (VMP) has been identified in our laboratory. This study aims to determine how
      stimulus load modulates recognition processing of digits. METHODS: ERPs were
      recorded from 117 healthy right-handed subjects during a delayed matching-to
      sample paradigm, using number stimuli that were either low load (three digits
      long) or high load (five digits long). The bootstrap method [R. Srebro, A
      bootstrap method to compare the shapes of two scalp fields, Electroenceph. Clin.
      Neurophysiol. 100 (1996) 25-32.] was employed to evaluate the topographic
      features of the VMP revealed in the current source density (CSD) maps. RESULTS:
      Response times were significantly shorter for matching stimuli than for non
      matching stimuli only for low loads; longer response times were related to higher
      loads compared to low loads only for matching stimuli. The high loads were
      related to larger ERP responses. The ERP was significantly smaller for matching
      than for non-matching three-digit numbers, but not for five-digit numbers. The
      ERP was also reduced to the test stimuli compared to sample stimuli regardless of
      stimulus load. Both temporal and frontal regions were involved in the recognition
      of the digit stimuli, and the left hemisphere was more active in the non-matching
      processing of digits. CONCLUSIONS: The VMP spatial pattern in addition to its
      amplitude is sensitive to stimulus load in the encoding process.

PMID- 9774728
TI  - The C4b-binding protein-protein S interaction is hydrophobic in nature.
AB  - C4b-binding protein (C4BP) is a major regulatory molecule of the complement
      system. By forming a non covalent complex with the anticoagulant cofactor protein
      S (PS), it also plays an important role in blood coagulation. C4BP is composed of
      one beta-chain and seven alpha-chains that are essentially built from complement
      control protein (CCP)-modules. Our group has previously reported that the first
      (N-terminal) CCP module of the beta-chain (betaCCP1) contains the entire binding
      site for protein S. We now investigate further the binding of protein S to C4BP
      and show that the complex formation is essentially dependent on hydrophobic
      forces with minor contribution from electrostatic interactions. This result is in
      agreement with homology modeling experiments carried out in conjunction with
      inter-species sequence comparison and theoretical enumeration of potential
      binding sites. These methods pinpoint a solvent exposed hydrophobic cluster at
      the surface of the betaCCP1 module that is of crucial importance for the binding
      process.

PMID- 9774729
TI  - Reactivation kinetics of 5,5'-dithiobis-(2-nitrobenzoic acid)-modified creatine
      kinase reactivated by dithiothreitol.
AB  - The reduction of 5,5'-dithiobis-(2-nitrobenzoic acid)-modified creatine by
      dithiothreitol has been studied using the kinetic theory of the substrate
      reaction during modification of enzyme activity as previously described by C.L.
      Tsou (Adv. Enzymol. Rel. Areas Mol. Biol. 61 (1988) 381-436). The results show
      that the modified creatine kinase can be fully reactivated by an excess
      concentration of dithiothreitol in a monophasic kinetic course. The presence of
      ATP or the transition-state analogue markedly slows the apparent reactivation
      rate constant, while creatine shows no effect. The substrates creatine-ADP-Mg2+
      can induce conformational changes of the modified enzyme but adding NO-3 cannot
      induce further changes that occur with the native enzyme. The reactive cysteines'
      location and role in the catalysis of creatine kinase are discussed. It is
      suggested that the cysteine may be located in the hinge area of the two domains
      of creatine kinase. The reactive cysteine of creatine kinase may play an
      important role not in the binding to the transition-state analogue but in the
      conformational changes caused by the transition-state analogue.

PMID- 9774730
TI  - Fixation behavior in observation and imitation of human movement.
AB  - This paper describes experiments performed with 40 subjects wearing an eye
      tracker and watching and imitating videos of finger, hand, and arm movements. For
      all types of stimuli, the subjects tended to fixate on the hand, regardless of
      whether they were imitating or just watching. The results lend insight into the
      connection between visual perception and motor control, suggesting that: (1)
      people analyze human arm movements largely by tracking the hand or the end-point,
      even if the movement is performed with the entire arm, and (2) when imitating,
      people use internal innate and learned models of movement, possibly in the form
      of motor primitives, to recreate the details of whole-arm posture and movement
      from end-point trajectories.

PMID- 9774731
TI  - Inter-isoformal regulation of nitric oxide synthase through heteromeric
      dimerization.
AB  - Biochemical characterization of neuronal nitric oxide synthase (nNOS) has
      demonstrated a unique complexity with the native protein being a homodimer. To
      cast light on its enzyme structure-activity relationship, inactive nNOS,
      generated by mutation of (Lys732-Lys-Leu) to (Asp732-Asp-Glu) (Watanabe et al.,
      FEBS Lett., 403 (1997) 75-78), and active nNOS were co-expressed using the Sf9
      and COS-7 cell expression system. Co-transfectants of active and inactive nNOS
      resulted in attenuation of Ca2+/calmodulin (CaM) dependent NOS enzyme activity to
      a level 46.4+/-4.30% as much as active homomeric enzyme. Dimerization between
      active and inactive nNOS was observed by low temperature SDS-PAGE in the co
      transfectants. The dimerization and attenuation of Ca2+/CaM dependent activity
      were not observed when active and inactive nNOS were combined in vitro,
      indicating that nNOS dimerization occurs intracellularly to form an active
      enzyme. Furthermore, we co-expressed inactive nNOS with active inducible NOS
      (iNOS) to analyze inter-isoformal regulation of NOSs. Interestingly, inactive
      nNOS also showed similar effects on enzyme activity and heteromeric dimerization
      against iNOS, thus indicating that inter-isoformal regulation of the two isoforms
      might also be involved in control of neuron function.

PMID- 9774732
TI  - The specific dopamine uptake inhibitor GBR 12783 improves learning of inhibitory
      avoidance and increases hippocampal acetylcholine release.
AB  - The specific dopamine uptake inhibitor, GBR 12783 was tested on the retention
      performance of a one-trial passive avoidance test. For a moderate electric shock
      intensity, GBR 12783 (10 mg/kg), injected before acquisition session, improved
      retention performance. Scopolamine (0.125-0.5 mg/kg) completely blocked the
      promnesic effect of GBR 12783. Moreover, GBR 12783 increased hippocampal
      acetylcholine release in vivo. These data suggest that the promnesic effect of
      GBR 12783 is mediated by an increase in the septo-hippocampal cholinergic
      transmission.

PMID- 9774733
TI  - Parallel visual search is not always effortless.
AB  - Serial visual search can become parallel with practice. We tested whether this
      parallelisation is accompanied by a transition from an attentive to a pre
      attentive and thus effortless mode of visual perception. While
      psychophysiological indicators of attentional effort (galvanic skin conductance,
      muscle tonus) reflected the distinction between serial and parallel search modes,
      they did not follow the perceptual changes during learning. Despite the
      perceptual parallelisation with practice, the attentional load remained high for
      initially serial tasks.

PMID- 9774734
TI  - Sodium chloride enhances markedly the thermal stability of thermolysin as well as
      its catalytic activity.
AB  - Thermolysin, a thermophilic metalloproteinase, is markedly activated in the
      presence of high concentrations (1-5 M) of neutral salts. The activity increases
      in an exponential fashion with increasing salt concentration, and is enhanced 13
      15 times with 4 M NaCl at pH 7.0 and 25 degreesC (K. Inouye, Effects of salts on
      thermolysin: activation of hydrolysis and synthesis of N-carbobenzoxy-l-aspartyl
      l-phenylalanine methyl ester, and a unique change in the absorption spectrum of
      thermolysin, J. Biochem. 112 (1992) 335-340). In this study, the effect of NaCl
      on the thermal stability of thermolysin has been examined at 60-85 degreesC. The
      activation energy, Ea, for the thermal inactivation is 15 kcal/mol at 0 M NaCl,
      and increases up to 30-33 kcal/mol by the addition of 0. 5-1.5 M NaCl. Further
      increase in [NaCl] decreases the Ea value, and at 4 M NaCl it is almost the same
      as that at 0 M NaCl. Thermolysin at 0.5-1.5 M NaCl is twice as heat-stable as in
      the absence of NaCl. The NaCl dependence of the stability is different from that
      of the activity, suggesting that the effects of NaCl on activity and stability
      are independent. Thermolysin has been demonstrated to be not only a thermophilic
      enzyme but also a highly halophilic one.

PMID- 9774735
TI  - MEG correlates of categorical perception of a voice onset time continuum in
      humans.
AB  - Event-related magnetic fields (ERFs) were recorded from the left hemisphere in
      nine normal volunteers in response to four consonant-vowel (CV) syllables varying
      in voice-onset time (VOT). CVs with VOT values of 0 and +20 ms were perceived as
      /ga/ and those with VOT values of +40 and +60 ms as /ka/. Results showed: (1) a
      displacement of the N1m peak equivalent current dipole toward more medial
      locations; and (2) an abrupt reduction in peak magnetic flux strength, as VOT
      values increased from +20 to +40 ms. No systematic differences were noted between
      the 0 and +20 ms stimuli or between the +40 and +60 ms CVs. The findings are in
      agreement with the results of multiunit invasive recordings in non-human primates
      regarding the spatial and temporal pattern of neuronal population responses in
      the human auditory cortex which could serve as neural cues for the perception of
      voicing contrasts.

PMID- 9774736
TI  - Analysis of thermal stability of soya globulins using monoclonal antibodies.
AB  - The epitopes of two monoclonal antibodies (Mabs), one raised to soya glycinin
      (IFRN 0025) and one to beta-conglycinin (IFRN 0089), have been defined. The
      epitope of 0025 corresponds to residues 86-104 of the acidic polypeptide of
      glycinin A1aB1b and lies at the C terminus of the proteolytic intermediate known
      as glycinin-T, whilst that of 0089 corresponds to residues 78-84 in the acidic
      extension present in the alpha' subunit of beta-conglycinin. As the Mabs bind to
      synthetic peptides corresponding to the epitope regions both epitopes can be
      considered as being continuous in nature. The regions recognised correspond to
      surface loops, which are probably flexible in nature. Both Mabs were used to
      investigate thermally induced conformational changes in soya globulins. Thermally
      treated glycinin was recognised more strongly than native protein, possibly due
      to disruption of the disulphide bond joining the acidic and basic polypeptides.
      Disruption could increase epitope accessibility, as could the conformational
      changes associated with denaturation. The binding of anti-beta-conglycinin Mab
      0089 was unaffected by heating, suggesting that its epitope remains on the
      surface of the aggregates formed on heating. This study demonstrates that Mabs
      with defined specificities can be sensitive probes for monitoring local
      conformational changes within a protein molecule during thermal denaturation.

PMID- 9774737
TI  - Dose-dependent action of glucose on memory processes in women: effect on serial
      position and recall priority.
AB  - Previous research has shown that glucose can enhance memory in animals and
      humans. In humans, the facilitative effect of glucose is best observed with
      declarative memory tasks in older subjects. While the memory-enhancing action of
      glucose is well established, the underlying physiological mechanisms and the
      specific aspects of memory that are modulated by glucose in humans are not well
      understood. The present study sought to examine the effects of glucose on memory
      in young women using a memory paradigm sensitive to specific encoding and
      retrieval strategies. The glucose dose was adjusted for the weight of each
      participant in order to generate a dose response curve covering most doses used
      in previous studies. The results showed that 300 mg/kg glucose enhanced the
      primacy effect as defined by the recall of the first five items of the lists.
      However, none of the doses of glucose produced changes in the recall priority
      given to primacy items. The effect of glucose appears to be localized on the
      recall primacy effect, suggesting that glucose acts on precise memory operations.
      This improvement, however, is independent of the order in which subjects recalled
      the words. Cholinergic drugs have been shown to alter the recall of the primacy
      part of word lists and this observation is consistent with the hypothesis that
      glucose acts on memory through an interaction with brain cholinergic systems.

PMID- 9774738
TI  - Purification and substrate specificity of an angiotensin converting elastase-2
      from the rat mesenteric arterial bed perfusate.
AB  - A soluble angiotensin (Ang) II-generating enzyme has been purified to homogeneity
      from the rat mesenteric arterial bed (MAB) perfusate by a combination of gel
      filtration and affinity chromatographies. The enzyme is a glycoprotein of 28.5
      kDa (SDS-PAGE), whose N-terminal sequence is identical with that of the rat
      pancreatic elastase-2; therefore the enzyme will henceforth be referred to as rat
      MAB elastase-2. When Ang I was used as the substrate, the enzyme specifically
      released Ang II and the dipeptide His-Leu (Km=36 microM; Kcat=1530 min-1). The
      catalytic efficiency (Kcat/Km=42.5 min-1 microM-1) of this reaction was
      comparable to those of other known Ang I-converting enzymes. The proteolytic
      specificity of the purified enzyme toward mellitin, oxidized insulin B chain,
      somatostatin-14 and renin substrate tetradecapeptide suggested that the enzyme
      substrate interaction was defined by an extended substrate binding site, typical
      of elastases-2 of pancreatic origin. According to the sensitivity of the rat MAB
      elastase-2 to various inhibitors this enzyme could be described as a member of
      the chymostatin-sensitive group of Ang II-forming serine proteases. The
      localization and biochemical properties of this enzyme suggest that it might play
      a role in the regional control of vascular tonus.

PMID- 9774739
TI  - Hydrophobilization of esterase by genetic combination with polyproline or
      polytyrosine at the carboxyl terminal.
AB  - Polyproline (Poly-Pro) that is an amphiphilic polypeptide, or polytyrosine (Poly
      Tyr) that is a hydrophobic polypeptide, were connected to the carboxy terminus of
      Pseudomonas sp. esterase by the recombinant DNA technique. The hydrophobicity of
      the esterase was enhanced by the introduction of Poly-Pro or Poly-Tyr, and also
      by increasing chain length of the polypeptides. Poly-Tyr increased the
      hydrophobicity of esterase more than Poly-Pro. Poly-Tyr induced significant
      conformational change of fusion esterase, but Poly-Pro did not. Consequently, the
      introduction of Poly-Tyr led to loss of activity of the fusion enzyme to a
      negligible level. On the other hand, the Poly-Pro-fusion-esterase retained
      enzymatic activity and the hydrolytic activity (kcat/Km) of the fusion esterase
      carrying 40 proline residues (esterase-Pro40) relative to that of the wild-type
      esterase with the substrates p-nitrophenyl-propionate, -pentanoate, and 
      hexanoate was 1.76, 1.95, and 4.7, respectively. The results could be explained
      in terms of easier access of long-chain carboxylate to the fusion esterase
      compared to the wild-type esterase in aqueous solution.

PMID- 9774740
TI  - Structure of the mouse calpain small subunit gene.
AB  - The calpains comprise a family of heterodimeric (80+28 kDa) Ca2+-dependent
      cysteine proteases, probably having roles in signal transduction and cytoskeletal
      remodelling. We describe cloning and sequencing of the 28 kDa calpain subunit
      cDNA from mouse (coding for 268 amino acids), and characterization of its gene.
      The gene spans 7 kb and contains 11 exons. The promoter region, like those of
      other calpain genes, lacks an obvious TATA box, but contains several Sp1 binding
      sites.

PMID- 9774741
TI  - Gene duplication and fusion have occurred frequently in the evolution of
      phosphagen kinases--a two-domain arginine kinase from the clam Pseudocardium
      sachalinensis.
AB  - In contrast to the 40 kDa arginine kinases from Molllusca and Arthropoda, the
      adductor muscle of the marine clam Pseudocardium sachalinensis contains an
      unusual arginine kinase consisting of an 86 kDa subunit. The cDNA encoding the 86
      kDa arginine kinase was amplified by PCR and the cDNA-derived amino acid sequence
      of 724 residues was determined. The exact molecular mass for the protein was
      calculated to be 80941 Da. The amino acid sequence clearly indicates that
      Pseudocardium arginine kinase has a two-domain structure: the first domain
      residues 1-363 and the second domain 364-724. The two domains, which are
      separated by an intron of 176 bp in the gene, show 62% amino acid sequence
      identity. This two-domain arginine kinase from a mollusc represents yet another
      multiple-domain enzyme observed in the phosphagen kinase enzyme family. Two
      domain and three-domain enzymes have been observed in three other diverse
      invertebrate groups. Thus, it is clear that gene duplication and subsequent
      fusion have occurred frequently, and likely independently, during the course of
      the evolution of this enzyme family. Comparison of the amino acid sequence in the
      GS region (a possible candidate for the guanidine substrate recognition site in
      the phosphagen kinase family) suggests that the first domain of Pseudocardium
      arginine kinase might not retain a complete enzyme activity, because the Asp-7 in
      the GS region, which is assumed to be involved in the recognition of the positive
      charge of arginine, was replaced by a Gly residue in the first domain.

PMID- 9774742
TI  - pzl-1 encodes a novel protein phosphatase-Z-like Ser/Thr protein phosphatase in
      Neurospora crassa.
AB  - The gene and cDNA of a novel protein phosphatase were cloned from Neurospora
      crassa. The pzl-1 gene encompasses three introns and is localized to the left arm
      of chromosome I between cyt-21 and Fsr-12. It encodes a protein of 58.3 kDa
      containing a Ser/Pro rich N-terminal segment, and a C-terminal domain that is
      similar to the catalytic subunit of type 1 protein phosphatases. The first 51
      amino acid residues, including a potential N-myristoylation site, as well as the
      C-terminal domain (about 300 residues) have a high level of sequence identity
      with yeast PPZ phosphatases. However, residues 52-208 do not share high
      similarity with other proteins. The mRNA of pzl-1 was detected in all phases of
      asexual development of the filamentous fungus.

PMID- 9774743
TI  - Sequence of the cry11Bb11 gene from Bacillus thuringiensis subsp. medellin and
      toxicity analysis of its encoded protein.
AB  - The nucleotide sequence of the cry11Bb1 gene from Bacillus thuringiensis subsp.
      medellin was determined. The corresponding protein has a deduced molecular mass
      of 88.2 kDa, and is 60.9% and 83% identical to the proteins Cry11Aa1 and
      Cry11Ba1, respectively. The Cry11Bb1 protein contains five repetitive blocks of
      16 amino acids at the C terminal part. It is highly toxic to first instar
      laboratory reared Aedes aegypti, Anopheles albimanus and Culex quinquefasciatus
      larvae.

PMID- 9774744
TI  - Molecular characterization of the Drosophila melanogaster gene encoding the
      pterin 4alpha-carbinolamine dehydratase.
AB  - We have isolated and characterized the cDNA and the genomic DNA encoding
      Drosophila melanogaster pterin 4alpha-carbinolamine dehydratase (PCD). The amino
      acid sequence deduced from the cDNA sequence was very similar to those of PCDs
      previously reported in other species (19-57% identity). The protein coding region
      of the cDNA was expressed in E. coli as a histidine fusion protein, and the
      expressed protein proved to have PCD activity. The characterization of the
      Drosophila genomic clone revealed that the Drosophila PCD gene is interrupted by
      two introns. The potential promoter region, deduced from the determination of the
      transcription start point (tsp), lacks the distinct TATAAA box consensus
      sequence.

PMID- 9774745
TI  - Cloning of cDNAs encoding new peptides of the dermaseptin-family.
AB  - Dermaseptins are a group of basic (lysine-rich) peptides, 27-34 amino acids in
      length and involved in the defense of frog skin against microbial invasion. By
      using a degenerated oligonucleotide primer binding to the 5'-untranslated region
      of previously characterized cDNAs of these peptides, it was possible to identify
      new members of the dermaseptin family in the South American frogs Agalychnis
      annae and Pachymedusa dacnicolor. Amino acid alignment and secondary structure
      prediction reveals, that only five of the deduced peptides can be supposed to be
      also functional homologs to the known dermaseptins from Phyllomedusa bicolor and
      Phyllomedusa sauvagei. The remaining six peptides described in this paper have
      not been isolated and characterized yet.

PMID- 9774746
TI  - Leukocyte count and aggregation during the evolution of cerebral ischemic injury.
AB  - We evaluated leukocyte aggregation by means of the leukergy test and count in 26
      patients with atherothrombotic stroke and in 10 patients with transient ischemic
      attacks. The evaluation was performed within 24 h from the onset of symptoms and
      then repeated on day 2, 4, 6 and 8. Data were compared with those of 10 healthy
      controls. Stroke patients were followed until day 30 when a clinical examination
      and brain computed tomography were performed to evaluate the extent and outcome
      of cerebral damage. Both leukocyte aggregation and count were significantly
      increased in stroke patients with respect to controls. While leukocyte count was
      not able to differentiate the severity of neurological impairment in stroke
      patients, leukocyte aggregation was significantly higher in major than in minor
      stroke patients on days 2 and 4 (p < 0.05). Moreover, while values of leukocyte
      count recorded at entry remained substantially stable in the following
      determinations in all groups, leukocyte aggregation showed a significant increase
      (p < 0.05) on day 4 with respect to all the other determinations in major stroke
      patients. These findings show that the extent and temporal profile of changes in
      leukocyte count and aggregation are different in patients with cerebrovascular
      disease and suggest an involvement of altered leukocyte rheology in the
      development of cerebral ischemic injury.

PMID- 9774747
TI  - Increasing levels of leukocyte-derived inflammatory mediators in plasma and cAMP
      in platelets during follow-up after acute cerebral ischemia.
AB  - Inflammatory mediators secreted by activated leukocytes play a role in the
      pathogenesis of atherosclerosis. They may also affect the production of
      vasodilatory and platelet antiaggregatory factors such as nitric oxide (NO) and
      prostacyclin (PGI2) from the vascular endothelium. Production of NO and PGI2, the
      effecs of which are mediated by cyclic 3',5'-guanosine monophosphate (cGMP) and
      cyclic 3',5'-adenosine monophosphate (cAMP), respectively, is disturbed in
      atherosclerosis, whereas increased NO levels have been found in acute cerebral
      ischemia. To investigate leukocyte activation and its possible influence upon
      endothelial function in cerebral ischemia we measured plasma neutrophil
      gelatinase-associated lipocalin (NGAL) and soluble tumor necrosis factor receptor
      protein-1 (sTNFR-1) by ELISA, and intraplatelet cAMP and cGMP by radioimmunoassay
      in 59 patients with acute ischemic stroke or transient ischemic attack (mean age
      71 years, 27 males) and after a 1-year follow-up in 57/59 (97%) patients. NGAL
      (152 +/- 58 vs. 126 +/- 48 microgram/l), sTNFR-1 (3.50 +/- 2.2 vs. 2.59 +/- 1.31
      microgram/l), and cAMP (5.12 +/- 1.71 vs. 4.06 +/- 0.92 pmol/10(9) platelets)
      were higher (p < 0.001) after follow-up than in acute cerebral ischemia. At
      follow-up sTNFR-1 and cGMP partially correlated (r = 0.31; p < 0.05), controlling
      for age and platelet count. In conclusion, plasma NGAL and sTNFR-1 and
      intraplatelet AMP increase after acute cerebral ischemia, indicating chronic
      inflammatory activity and endothelial activation. Plasma sTNFR-1 levels are
      related to intraplatelet cGMP levels.

PMID- 9774748
TI  - Cysteinyl-leukotriene levels in intracerebral hemorrhage: an edema-promoting
      factor?
AB  - In 12 operatively (stereotactic aspiration and recombinant tissue-type
      plasminogen activator, rTPA) and 5 conservatively treated patients with
      spontaneous intracerebral hemorrhage the amounts of cysteinyl-leukotriene (cys
      LT) released by blood-brain cell contact were measured by the urinary excretion
      of their metabolites during treatment. The mean cys-LT release before treatment
      was 14.51 +/- 1.13 pg/mg creatinine/ml hematoma volume. The urinary cys-LT
      excretion at the end of the measurements was significantly lower in the
      operatively treated group than in the patients with conservative therapy (p <
      0.05). We also found a significant correlation between the perifocal edema volume
      and the amount of cys-LT measured in patients' urine (p < 0.01). In an additional
      animal experiment using dissociated rat brain cells plasmin was excluded as an
      activator for cerebral cys-LT formation, which emphasizes that rTPA did not
      influence cys-LT formation.

PMID- 9774749
TI  - Migraine with aura and right-to-left shunt on transcranial Doppler: a case
      control study.
AB  - Right-to-left shunt (RLS), usually due to patent foramen ovale, is a well
      established risk factor for ischemic stroke in young patients, while the role of
      migraine as an independent factor is still debated. We evaluated 44 patients
      suffering from migraine with aura, and compared them with 73 patients younger
      than 50 with focal cerebral ischemia, and 50 controls, asymptomatic for
      cerebrovascular disease, and without a history of migraine. All the subjects
      underwent bilateral transcranial Doppler with injection of contrast medium in an
      antecubital vein. The test was performed during normal ventilation and during
      Valsalva maneuver, recording both the middle cerebral arteries and the basilar
      artery. Criteria for diagnosing RLS was the presence of at least 3 microbubbles
      within 15 s from injection. Eighteen out of 44 migraine patients (41%) showed
      RLS, as opposed to 8 of 50 controls (16%) (p < 0.005). Twenty-six out of 73
      patients with cerebral ischemia had RLS (35%). We conclude that the prevalence of
      RLS in patients with migraine with aura is significantly higher than in normal
      controls, and is similar to the prevalence of RLS in young patients with stroke.
      These findings could be helpful in understanding the relationship between
      migraine and stroke.

PMID- 9774750
TI  - Heparin treatment in acute cerebral sinus venous thrombosis: a retrospective
      clinical and MR analysis of 42 cases.
AB  - The only randomized data on heparin treatment in acute cerebral sinus venous
      thrombosis (CSVT) are derived from a small number of patients. The rate of
      intracranial hemorrhages as a complication of high-dose heparin treatment is
      still unknown. This retrospective study evaluates the clinical features,
      neuroimaging monitoring and outcome of 42 patients with proven CSVT. Diagnosis
      was established by DSA, CT, MR tomography and MR angiography. All patients
      received heparin intravenously guided by doubling the aPTT value for 3 weeks,
      followed by oral anticoagulation. Partial or complete recanalization was found in
      36 cases. 40 patients improved clinically, in 26 of them complete recovery was
      observed. One patient deteriorated and developed an apallic syndrome, one further
      patient died of septic multiorgan failure. Only in one patient was hemorrhagic
      transformation of infarcted brain tissue observed but without clinical
      deterioration.

PMID- 9774751
TI  - Significance of carotid restenosis following endarterectomy.
AB  - BACKGROUND AND PURPOSE: The clinical significance of restenosis after carotid
      endarterectomy as detected by duplex ultrasound has not been clearly established.
      To address this problem, we retrospectively evaluated the experience at two
      university-affiliated hospitals. METHODS: All charts of patients with carotid
      endarterectomies between June 1987 and April 1995 were reviewed. Inclusion
      required neurological assessment and postoperative duplex ultrasound. Exclusion
      was based on a known source of cardioembolic disease, or recent (<6 months)
      myocardial infarction. Primary clinical endpoints were ipsilateral transient
      ischemic attack (TIA) or ischemic stroke. Contributing vascular risk factors were
      also identified. The effect of restenosis on event-free survival was analyzed
      using life tables and Gehan-Wilcoxon rank sum tet. Logistic regression was used
      to identify independent risk factors for restenosis and vascular events. RESULTS:
      One hundred and eighty-seven patients were identified who underwent a total of
      207 endarterectomies. Mean follow-up was 30.4 +/- 20.9 months during which a
      total of 64 vascular events, including 42 TIAs, 18 strokes, and 4 vascular deaths
      occurred. Of these 21 TIAs and 8 strokes were ipsilateral to the side of
      endarterectomy. Event rates were compared for patients with ipsilateral high-
      (>/=50%) and low-grade (<50%) restenosis. These two groups were comparable in
      terms of baseline risk factors. There was no significant difference in vascular
      event rates (for either ipsilateral events or events in any vascular territory)
      between the group with high- and low-grade restenosis. Nor was any such
      difference in event rates shown for patients who showed ipsilateral progression
      of carotid disease on serial ultrasound. However, patients operated for
      symptomatic carotid disease had a significantly higher risk of neurological
      events (p = 0.035). Logistic regression failed to disclose any other risk factors
      that were independently predictive of either restenosis or vascular events during
      follow-up. CONCLUSION: This study does not show a difference in vascular event
      rates for higher grades of carotid restenosis after carotid endarterectomy.
      Routine surveillance with carotid ultrasound does not appear to identify patients
      at higher risk for postoperative cerebrovascular events.

PMID- 9774752
TI  - Clinical predictors of early embolic recurrence in presumed cardioembolic stroke.
AB  - BACKGROUND: We determined clinical predictive factors of in-hospital embolic
      recurrence in presumed cardioembolic stroke patients by means of multivariate
      analysis based on clinical and neuroimaging prognostic variables assessed within
      48 h of stroke onset. METHODS: Data of 347 consecutive patients with presumed
      cardioembolic stroke included in a prospective stroke registry were collected.
      Demographic characteristics, clinical events, and outcome in the recurrent and
      nonrecurrent embolization group were compared. The independent predictive value
      of each variable on the development of early embolic recurrence was analyzed in
      two multiple liner regression models - one based on eight demographic,
      anamnestic, and clinical variables and another based on 10 clinical,
      neuroimaging, and outcome variables. RESULTS: In-hospital recurrent embolization
      was diagnosed in 25 (6.9%) patients. The latency period was 12.1 days. The
      overall in-hospital mortality was 70.8% in the recurrent embolization group and
      24.4% in the nonrecurrent embolization group (p < 0.001). Alcohol abuse, the
      combination of hypertension, valvular heart disease, and atrial fibrillation,
      nausea and vomiting, and previous cerebral infarction were predictors of
      recurrent embolization in the model based on clinical variables. In addition to
      these four variables, cardiac events were selected in the model based on
      clinical, neuroimaging, and outcome variables. CONCLUSIONS: A small number of
      clinical features that can be easily obtained on the patient's initial assessment
      may help clinicians to identify a subgroup of patients with cardioembolic stroke
      at the highest risk of developing early recurrent brain or systemic embolization.

PMID- 9774754
TI  - Non-sibilant fricatives in English: spectral information above 10 kHz.
AB  - The purpose of this study is to explore the contribution of higher frequencies to
      fricative consonant classification in Australian English. The spectral range
      above 10 kHz is analysed in an attempt to provide better classifications of the
      dental and the labiodental fricatives. A comparison is made between real-word
      data and data from a controlled-word context. Although results for the controlled
      word context suggest that spectral information above 10 kHz may be of use in
      classifying [f] correctly, these results are not repeated for the real-word data.
      Moreover, classification of [f] and [q] using only the information above 10 kHz
      yields quite poor results. It is also shown that the results for the voiced
      dental and labiodental fricatives are not as promising as those for their
      voiceless counterparts.

PMID- 9774755
TI  - Do airstream mechanisms influence tongue movement paths?
AB  - Velar consonants often show an elliptical pattern of tongue movement in
      symmetrical vowel contexts, but the forces responsible for this remain unclear.
      We here consider the role of overpressure (increased intraoral air pressure)
      behind the constriction by examining how movement patterns are modified when
      speakers change from an egressive to ingressive airstream. Tongue movement and
      respiratory data were obtained from 3 speakers. The two airstream conditions were
      additionally combined with two levels of speech volume. The results showed
      consistent reductions in forward tongue movement during consonant closure in the
      ingressive conditions. Thus, overpressure behind the constriction may partly
      determine preferred movement patterns, but it cannot be the only influence since
      forward movement during closure is usually reduced but not eliminated in
      ingressive speech.

PMID- 9774756
TI  - Effects of contrastive emphasis on jaw opening.
AB  - This paper examines the effect of contrastive emphasis on the amount of vertical
      jaw displacement, as measured from X-ray microbeam data, for 3 American English
      speakers. Jaw opening in short utterances with one word emphasized (in initial,
      middle, and final positions) was compared with that of similar utterances with no
      words emphasized. The results suggest that emphasis involves not only a
      significant increase in jaw opening on the word emphasized but also possibly a
      reduction of jaw opening on the word following emphasis. Emphasis in addition may
      affect the amount of jaw opening of the utterance as a whole, in terms of a
      decrement in jaw opening on all the remaining words in the utterance following
      the emphasized word. The relationship between jaw opening and hierarchical levels
      of prosodic structure is tentatively discussed.

PMID- 9774757
TI  - Socioeconomic status and HRT use.

PMID- 9774758
TI  - The declining impact of race and insurance status on hormone replacement therapy.
AB  - OBJECTIVE: Socioeconomic barriers may limit the adoption of hormone replacement
      therapy, but little is known about recent trends in their influence. We evaluated
      trends in the impact of race and insurance status on national rates of hormone
      replacement therapy. DESIGN: We analyzed 32,608 physician office visits by
      nonpregnant women 40 years of age and older available from the 1989 through 1996
      National Ambulatory Medical Care Surveys. The proportion of visits with new or
      continuing use of noncontraceptive estrogens reported was the main outcome
      measured. Multiple logistic regression was used to evaluate the independent
      effects of year, race, and expected payment source on hormone replacement
      therapy. RESULTS: Overall, the report of hormone replacement therapy increased
      from 5.7% of visits in 1989-1990 to 10.9% in 1995-1996. In 1989-1990, hormone
      replacement therapy was less likely in nonwhite women (3.6% vs. 6.3% for whites)
      and in women with Medicaid coverage (1.3% vs. 8.4% for privately insured women).
      These differences diminished over time, particularly for women without menopausal
      symptoms. In 1989-1990, the adjusted odds ratio of hormone replacement in women
      without menopausal symptoms was 0.31 (95% confidence interval 0.2-0.5) in
      nonwhites compared with whites, but increased to 0.57 (0.4-0.8) by 1995-1996. In
      1989-1990, the adjusted odds ratio for hormone replacement among women with
      Medicaid was 0.31 (0.09-1.0) compared with those with private insurance. This
      ratio increased to 0.86 (0.5-1.4) by 1995-1996. CONCLUSIONS: Racial and payment
      source influences on hormone replacement therapy appeared to have lessened over
      time. Despite these changes substantial socioeconomic differences in treatment
      patterns remain to be addressed.

PMID- 9774759
TI  - Breast cancer risk among women under 55 years of age by joint effects of usage of
      oral contraceptives and hormone replacement therapy.
AB  - OBJECTIVE: To assess effects on breast cancer risk of exposure to both oral
      contraceptives and menopausal hormones, an increasingly common exposure. DESIGN:
      A case-control study of breast cancer among women under the age of 55 years in
      Atlanta, GA involving 1,031 cases and 919 population controls was conducted.
      RESULTS: Ever use of oral contraceptives was associated with a relative risk of
      1.1 (95% 0.9-1.4), whereas the relative risk for hormone replacement therapy was
      0.9 (95% CI 0.7-1.2). Seventeen percent of the cases versus 19% of the population
      controls reported exposure to both agents, resulting in a relative risk of 1.0
      (95% CI 0.7-1.4) relative to those unexposed to either preparation. Although
      there was little variation in risk associated with joint effects by either age or
      race, there were statistically nonsignificant elevations in risk for this
      exposure among women who had experienced a natural menopause (relative risk =
      2.0, 95% CI 0.7-5.6), were relatively thin (relative risk = 1.5, 0.8-3.0), or who
      had a first degree relative with breast cancer (relative risk = 2.0, 0.6-7.0).
      When joint effects of longer term use of both agents were considered, subjects
      who reported use of oral contraceptives for 10 or more years and hormone
      replacement for 3 or more years had a relative risk of 3.2 (95% CI 1.4-7.4)
      compared with nonusers of either preparation. CONCLUSIONS: Although our results
      must be cautiously interpreted given small numbers within subgroups, they raise
      concern and emphasize the need for further evaluation on breast cancer risk of
      the increasingly common exposure to both oral contraceptives and hormone
      replacement therapy.

PMID- 9774760
TI  - Comparison of continuation of postmenopausal hormone replacement therapy:
      transdermal versus oral estrogen.
AB  - OBJECTIVE: To determine possible differences in the rate at which hormone
      replacement therapy (HRT) is continued among postmenopausal women treated
      initially with transdermal estradiol versus those treated initially with oral
      conjugated estrogens. DESIGN: A retrospective database search for prescription
      use. SETTING: Northern California facilities of Kaiser Permanente, a health
      maintenance organization. PATIENTS: Women aged > or = 45 years who filled index
      prescriptions for HRT during 1995 for either 0.05 mg transdermal estradiol
      semiweekly or 0.625 mg oral conjugated estrogen daily. All had filled
      prescriptions for medroxyprogesterone acetate (MPA) on the same day as the index
      estrogen prescription. RESULTS: We found statistically significantly greater
      relative risk (RR) of discontinuation among women whose HRT began with
      transdermal estradiol compared with women whose HRT began with oral conjugated
      estrogens [RR = 2.6, 95% confidence interval (CI) = 1.8-3.8]. After multiple
      adjustments, RR was 2.7 (95% CI = 1.8-3.9). Complete discontinuation of HRT
      treatment accounted for most of the stopping we observed, but more women switched
      from transdermal to oral (25% of those discontinuing this route) than switched
      from oral to transdermal (0.9% of those discontinuing this route). Risk of
      discontinuation was not associated with whether prescriber was a gynecologist (RR
      = 1.2, 95% CI = 0.9-1.7). Type of progestin schedule (cyclic vs. continuous
      combined) also was not a predictor for discontinuation (RR = 0.9, 95% CI = 0.8
      1.0). Older age at start of treatment was associated with discontinuation (RR =
      1.1, 95% CI = 1.0-1.2) for every additional 5 years of age. CONCLUSION: Among
      women starting HRT, those using a semiweekly transdermal estradiol regimen have a
      lower rate of continuation than do those using oral estrogen daily.

PMID- 9774761
TI  - Effects of oral and transdermal hormone replacement therapy on lipoprotein(A) and
      lipids: a randomized controlled trial.
AB  - OBJECTIVE: Our purpose was to compare the effect of oral and transdermal hormone
      replacement therapy on lipoprotein(a) and other plasma lipids in healthy
      postmenopausal women. DESIGN: A total of 120 postmenopausal women were enrolled
      in a prospective randomized controlled study, and allocated either to transdermal
      17 beta-estradiol (50 micrograms/day) or to oral conjugated estrogen (0.625
      mg/day). Forty-one age-matched women were used as the reference group. Plasma
      lipids and lipoproteins were determined every 3 months and differences were
      sought by statistical analysis. RESULTS: Plasma lipoprotein(a) dropped after 3
      months of treatment either with transdermal estradiol (p < 0.01) or oral estrogen
      (p < 0.01). Lipoprotein(a) was reduced by 12% and 22%, respectively. No further
      decreases were seen later on. Plasma total and low-density lipoprotein (LDL)
      cholesterol concentrations were decreased significantly with both treatments
      after 3 months of therapy. No difference was seen in the lowering effect on
      lipoprotein(a), LDL and total cholesterol concentrations between regimens. Plasma
      high-density lipoprotein (HDL) cholesterol and triglyceride concentrations
      increased throughout the study only in patients treated with oral estrogen.
      CONCLUSIONS: These data demonstrate that hormone replacement therapy reduces the
      concentration of lipoprotein(a) when given both orally and transdermally. The
      lowering effect is achieved quickly because the maximal effect is observed after
      3 months of therapy.

PMID- 9774762
TI  - Nandrolone decanoate causes pathologic changes in the uterus of surgically
      postmenopausal female cynomolgus macaques.
AB  - OBJECTIVE: To determine the effects of the androgenic anabolic steroid nandrolone
      decanoate on uterine endometrium and myometrium and on the mammary gland of
      female cynomolgus macaques by using morphologic, histomorphometric, and
      histopathologic determinations. DESIGN: Histologic and histomorphometric
      measurements were performed on uteri and mammary glands that were collected at
      necropsy from animals that had been used in a long-term experiment to examine the
      effects of nandrolone decanoate on bone and coronary arteries. The animals were
      surgically postmenopausal cynomolgus macaques randomized into four treatment
      groups: (a) intact sham ovariectomized (sham; n = 12), (b) ovariectomized (OVX; n
      = 15), (c) ovariectomized + nandrolone decanoate for 2 years (OVX + ND; n = 14),
      and (d) ovariectomized + nandrolone decanoate for 1 year, beginning 1 year after
      ovariectomy (OVX + NDdelay; n = 11). Intramuscular injections of nandrolone
      decanoate (25 mg every 3 weeks) were given to the two nandrolone-treated groups
      of animals (OVX + ND and OVX + NDdelay): one starting 3 weeks after ovariectomy
      and continuing for 2 years and the other group 1 year after ovariectomy. The sham
      and OVX groups were given an intramuscular injection of sterile vehicle every 3
      weeks. RESULTS: Nandrolone treatment was moderately uterotropic in all treated
      versus ovariectomized animals. Changes induced were an increase in uterine
      weight, endometrial thickness, and glandular area, and a high incidence of
      mucometra. Glandular architecture was altered by nandrolone treatment such that
      glands extended into the myometrium (producing an adenomyosis-like lesion).
      Mammary gland changes were mild and equivocal. CONCLUSION: Nandrolone induced
      pathologic changes in ovariectomized monkeys similar to adenomyosis in the
      uterus.

PMID- 9774763
TI  - Patient satisfaction with psychiatric treatment of menopausal women in a
      multidisciplinary women's midlife center.
AB  - OBJECTIVE: Menopause may be associated with new onset psychiatric symptoms or may
      exacerbate or heighten preexisting psychiatric problems in women. We present a
      model center for midlife women, with a multidisciplinary approach to treating
      this population, and patients' perceptions of satisfaction with treatment
      received during referral visits to an outpatient psychiatry clinic. DESIGN: In
      this study, 59 patients were referred from their primary care provider at the
      midlife center for evaluation by a faculty psychiatrist in an outpatient setting.
      A brief telephone interview was administered within 1 year of initial evaluation,
      using items from the Client Satisfaction Questionnaire-8 (CSQ-8) to assess
      patient satisfaction with psychiatric services received during the referral
      visits. Findings were based on responses provided by 50 women who were
      successfully contacted by telephone for the follow-up assessment. RESULTS: For
      this sample, the mean total client satisfaction score was 27.8 (s = 5.4) of a
      possible score of 32, which indicated that most women who were referred for
      psychiatric services reported a positive experience with the services provided by
      outpatient psychiatrists and reported being very satisfied with their treatment.
      CONCLUSIONS: We feel that this model center represents a unique way to identify
      and treat psychiatric disorders in a patient population that may be at high risk
      for depression and other psychiatric disorders.

PMID- 9774764
TI  - Treatment-seeking women at menopause: a comparison between two university
      menopause clinics.
AB  - OBJECTIVE: We wished to determine the expectations of women about the benefits of
      hormone replacement therapy (HRT) and how these expectations may be influenced by
      cultural factors and previous experience of disease by the patient or in their
      families. DESIGN: The attitudes of patients seeking HRT in Belfast, United
      Kingdom (n = 218) and Portland, USA (n = 100) were compared at their first clinic
      attendance using a questionnaire. Physical and mental health issues, previous use
      of HRT and continuance on treatment were compared. RESULTS: Belfast women were
      less healthy than their Portland counterparts, with a higher prevalence of
      cardiovascular disease and psychiatric disorders (p < 0.05). Belfast patients
      showed a significantly lower continuance with treatment (p < 0.01). Collectively,
      the patients ranked relief of menopausal symptoms as their main expectation from
      HRT followed by osteoporosis protection, psychiatric relief and cardioprotection.
      The Belfast group had higher expectations for the relief of
      psychological/psychiatric problems (p < 0.01). All women with a family history of
      cardiac disease or fractures were more concerned for the protective effects of
      HRT than those women with no relevant family history (p < 0.05). There were
      cultural difference in expectations from HRT with Belfast women expecting more
      psychological/psychiatric relief and therefore trying a greater number of
      preparations. CONCLUSIONS: These findings suggest that menopausal women in both
      countries are well informed about the potential protective benefits of HRT, and
      now expect an improvement in the quality of their lives well beyond the relief of
      menopausal symptoms.

PMID- 9774765
TI  - Attitudes toward menopause and hormone therapy among women with access to health
      care.
AB  - OBJECTIVE: To explore the relationship between women's attitudes toward menopause
      and hormone therapy and paradigms of menopause as a natural life event versus a
      biomedical phenomenon. DESIGN: Women (N = 2092) sampled from physicians'
      practices in Washington state completed mailed questionnaires with a response
      rate of 72%. RESULTS: Women's attitudes toward menopause were unrelated to their
      adoption of a biomedical versus developmental paradigm of menopause. In contrast,
      women's adoption of the view that menopause was an endocrine deficiency and that
      symptoms should be treated with hormones were correlated. Endorsement of the
      endocrine deficiency model of menopause was related to women's attitudes toward
      hormone therapy as more efficacious, less risky, and requiring daily use of a
      drug. Women's experiences of a hysterectomy and hormone use were associated with
      their attitudes. CONCLUSIONS: Women's attitudes toward menopause are
      multidimensional and not influenced wholly by adoption of a biomedical or
      developmental paradigm. Women embraced menopause as part of life and
      simultaneously accepted changes in their endocrine production. Attitudes toward
      hormone therapy were closely aligned with adoption of a biomedical view of
      menopause and use of hormone therapy.

PMID- 9774766
TI  - Incidence of sexual dysfunction in surgically menopausal women.

PMID- 9774767
TI  - Attention deficit hyperactivity disorder: unravelling the molecular genetics.

PMID- 9774768
TI  - Single genes and complex phenotypes.

PMID- 9774769
TI  - When less says more: clues from a missing Alzheimer-associated protein.

PMID- 9774770
TI  - Oscillating molecules and circadian clock output mechanisms.

PMID- 9774771
TI  - Anti-hyperactivity medication: methylphenidate and amphetamine.
AB  - How do 'stimulants' reduce hyperactivity in children and adults? How can drugs
      which raise extracellular dopamine result in psychomotor slowing of hyperactive
      children when dopamine is known to enhance motor activity, such as in Parkinson's
      disease? These apparent paradoxes are the focus of this brief review on the
      mechanism of action of stimulant medications used in the treatment of children,
      and of an increasing number of adults who meet diagnostic criteria for attention
      deficit hyperactivity disorder.

PMID- 9774772
TI  - Circumscribed lesion of the medial forebrain bundle area causes structural
      impairment of lymphoid organs and severe depression of immune function in rats.
AB  - Interactions between the immune system and the brain are a key element in the
      pathophysiology of diseases such as multiple sclerosis, neuroAIDS, and
      Alzheimer's, which affect large numbers of individuals and are associated with a
      high social cost. However, the neuroanatomical basis of brain-immune interactions
      has not been elucidated. We report that in Wistar rats of either sex bilateral
      electrolytic lesion of the medial forebrain bundle reduces body weight by 28% 7
      days after lesioning, and causes widespread infections, aphagia, adypsia,
      structural damage to the lymphoid organs and heavy depression of T lymphocytes
      cytotoxicity. The following alterations occur in the immune system after those
      lesions: the weight of the thymus, spleen and lymphonodes is reduced by 77.9%,
      49.1% and 48.4%, respectively. The thymus is atrophied and contains fewer
      lymphoid cells in the cortex than in the medulla. In the spleen the white pulp is
      reduced and lymphoid cells from periarteriolar zones and at the chords are almost
      absent. In lymph nodes cortical small lymphocytes are depleted and primary and
      secondary nodules and germinal centers all but disappear. Cytotoxicity of
      lymphocytes is reduced by 86.2% in the thymus, 77.6% in the spleen and 70.2% in
      lymph nodes. The critical area of lesion is at the medialmost portion of the
      medial forebrain bundle, at the preoptic area and rostral part of the anterior
      hypothalamus. We suggest that this area contains neural circuits that are crucial
      for keeping the structure of lymphoid organs and the functional integrity of the
      immune system.

PMID- 9774773
TI  - Two commonly expanded CAG/CTG repeat loci: involvement in affective disorders?
AB  - An association between bipolar affective disorder and CAG/CTG trinucleotide
      repeat expansions (TRE) has previously been detected using the repeat expansion
      detection (RED) method. Here we report that 89% of RED products (CAG/CTG repeats)
      > 120 nt (n = 202) detected in affective disorder patients as well as unaffected
      family members and controls correlate with expansions at two repeat loci, ERDA1
      on chromosome 17q21.3 and CTG18.1 on 18q21.1. In a set of patients and controls
      in which we had previously found a significant difference in RED size
      distribution, the frequency of expansions at the CTG18.1 locus was 13% in bipolar
      patients (n = 60) and 5% in controls (n = 114) (P < 0.07) with a significantly
      different size distribution (P < 0.03). A second set of patients were ascertained
      from 14 affective disorder families showing anticipation. Twelve of the families
      had members with RED products > 120 nt. The RED product distribution was
      significantly different (P < 0.0007) between affected (n = 53) and unaffected (n
      = 123) offspring. Using PCR, a higher frequency (P < 0.04) of CTG18.1 expansions
      as well as a different (P < 0.02) repeat size distribution was seen between
      affected and unaffected offspring. In addition, a negative correlation between
      RED product size and the age-of-onset could be seen in affected offspring (rs = 
      0.3, P = 0.05, n = 43). This effect was due to an earlier onset in individuals
      with long CTG18.1 expansions. No difference in ERDA1 expansion frequency was seen
      either between bipolar patients (35%, n = 60) and matched controls (29%, n =
      114), or between affected and unaffected offspring in the families. We conclude
      that expanded alleles at the CTG18.1 locus confers an odds ratio of 2.6-2.8 and
      may thus act as a vulnerability factor for affective disorder, while the ERDA1
      locus seems unrelated to disease.

PMID- 9774774
TI  - Growth-associated protein (GAP-43), its mRNA, and protein kinase C (PKC)
      isoenzymes in brain regions of depressed suicides.
AB  - The aim of this study was to investigate whether the previously observed adaptive
      changes in the monoaminergic receptors in post-mortem brains of depressed suicide
      victims are associated with alteration in some functional proteins involved in
      serotonergic neuronal signalling, namely PKC and GAP-43. Selected regions from
      ten brains of antidepressant-free depressed suicide victims and ten matched
      controls were used to examine the levels of GAP-43 protein, GAP-43 mRNA and PKC
      isoenzymes by Western blotting with monoclonal antibodies specific for these
      proteins. A major finding of the study was a significant decrease in GAP-43
      protein levels and its mRNA expression in prefrontal cortex (BA9) (by 24% and
      34%, respectively) of suicide brains compared to controls. No significant changes
      were found in GAP-43 protein or its mRNA in frontopolar cortex (BA10), amygdala,
      substantia nigra or putamen. Levels of PKC isoenzymes had a heterogenous regional
      distribution but were not significantly altered in any of the regions examined.
      Given the role of GAP-43 in the establishment and reorganization of synaptic
      connections, the finding of selective reduction of this protein in prefrontal
      cortex suggests that a dysfunctional synaptic organization in this region may be
      associated with depression and suicidal behaviour. This study provides the first
      evidence of an alteration in a protein related to the neuronal plasticity in the
      brain of depressed suicide victims.

PMID- 9774775
TI  - Dopamine DRD4 receptor polymorphism and attention deficit hyperactivity disorder.
AB  - A polymorphism in the dopamine receptor 4 gene (DRD4) has been related to novelty
      seeking, Tourette's syndrome, and attention deficit hyperactivity disorder
      (ADHD). The variability is in a 48-bp repeat in exon 3 of the gene (a
      transmembrane region). This study examined the relation of the 7-repeat (i.e.,
      high-risk) allele to questionnaire-based diagnoses of ADHD (both combined type
      and inattentive type). Several positive findings were obtained for ADHD
      inattentive type. In an association test, the 7-repeat allele occurred more
      frequently in children with ADHD-inattentive type than in control children. In
      genetically discordant sibling pairs, the sibling with a greater number of 7
      repeat alleles displayed more inattentive symptoms than his/her co-sibling with
      fewer 7-repeat alleles. For ADHD-combined type, the 7-repeat allele frequency was
      greater than that in the control sample. However, a quantitative transmission
      disequilibrium test yielded no significant linkage of the 7-repeat allele with
      hyperactive-impulsive symptoms. A categorical TDT yielded no significant
      findings, but the number of transmissions was small, especially for ADHD
      inattentive type.

PMID- 9774776
TI  - Evidence that the dopamine D4 receptor is a susceptibility gene in attention
      deficit hyperactivity disorder.
AB  - Attention deficit hyperactivity disorder (ADHD) is a common neurobehavioral
      problem afflicting 5-10% of children and adolescents and persisting into
      adulthood in 30-50% or more of cases. Family, twin, and adoption studies suggest
      genetic factors contribute to ADHD and symptoms of inattention, impulsivity, and
      hyperactivity. Because stimulant intervention is effective in reducing ADHD
      symptoms in about 70-80% of cases, molecular genetic investigations of genes
      involved in dopamine regulation are currently underway by many groups. In a case
      control study of the dopamine D4 receptor gene (DRD4) and ADHD, La Hoste and
      colleagues found an increase of a 7-repeat variant of a 48-bp VNTR in exon 3
      among ADHD subjects compared to controls. Swanson and colleagues replicated this
      finding in a sample of 52 ADHD probands and their biological parents using a
      haplotype relative risk analysis. Here, we describe linkage investigations of the
      VNTR and ADHD in affected sibling pair (ASP) families and singleton families
      using both the transmission disequilibrium test (TDT) and a mean test of identity
      by-descent (IBD) sharing. Using the TDT in the total sample, the 7 allele is
      differentially transmitted to ADHD children (P = 0.03) while the mean test
      revealed no evidence of increased IBD sharing among ASPs. In the current sample,
      the 7 allele attributes a 1.5-fold risk for developing ADHD over non-carriers of
      the allele estimated under a model described by Risch and Merikangas.

PMID- 9774777
TI  - Lack of an association between a dopamine-4 receptor polymorphism and attention
      deficit/hyperactivity disorder: genetic and brain morphometric analyses.
AB  - Although the etiology of attention-deficit/hyperactivity disorder (ADHD) is
      likely multifactorial, family, adoption, and twin studies suggest that genetic
      factors contribute significantly. Polymorphisms of the dopamine 4 receptor (DRD4)
      affect receptor binding, and one allele with seven tandem repeats in exon 3
      (DRD4*7R) has been associated with ADHD. We examined this putative association in
      41 children with severe ADHD and 56 healthy controls who were group matched for
      ethnicity and sex. The frequency of the DRD4*7R allele did not vary by diagnosis
      (0.220 vs 0.205 in patients and controls, respectively). Behavioral and brain
      anatomic MRI measures, previously found to discriminate patients from controls,
      did not differ significantly between subjects having and those lacking a DRD4*7R
      allele. These data do not support the reported association between DRD4*7R and
      the behavioral or brain morphometric phenotype associated with ADHD.

PMID- 9774778
TI  - C677T polymorphism in methylenetetrahydrofolate reductase gene and psychoses.
AB  - A common missense mutation of the methylenetetrahydrofolate reductase (MTHFR)
      gene (C677T) has been shown to be a risk factor for premature cardiovascular
      disease and neural tube defect. Deficient activity of MTHFR has also been
      implicated in the pathogenesis of psychiatric conditions such as schizophrenia
      and affective disorders. Arinami et al found an increased frequency of
      homozygosity for the mutated type (T677) of the MTHFR gene in schizophrenia and
      depression. We tried to replicate this finding in a sample of 343 patients with
      schizophrenia, 143 with bipolar disorder, 71 with unipolar depression, and 258
      controls; however, there was no significantly increased frequency of homozygosity
      for the T677 allele in any of the diagnostic groups, compared to the controls.
      Our results suggest that homozygosity for the T677 allele of the MTHFR gene is
      unlikely to play a major role in the pathogenesis of schizophrenia or affective
      disorders in our sample.

PMID- 9774779
TI  - The short variant of the polymorphism within the promoter region of the serotonin
      transporter gene is a risk factor for late onset Alzheimer's disease.
AB  - We analyzed a deletion/insertion polymorphism within the promoter region of the
      serotonin transporter gene (5-HTTPLR) in 81 patients with late onset Alzheimer's
      (AD) disease (mean age 70.02 +/- 8.13 years). Control groups included 81 normal
      subjects with comparable age (mean age 75.6 +/- 10.2) and 82 younger normal
      subjects (mean age 37.4 +/- 9.1). Statistical analysis showed a significant
      difference in the genotype and gene frequencies between the AD group and normal
      controls (chi 2 = 9.021; 2 d.f. and chi 2 = 5.59, 1 d.f., respectively, P < 0.05)
      due to the higher frequency of the L allele and the lower frequency of the s
      allele in controls than among AD patients. However, no differences were found in
      the genotype frequencies in older as compared to younger normal control groups
      (chi 2 = 0.337, 2 d.f. and P > 0.05). The present study confirms, in a different
      population, that the short variant of the 5-HTTPLR polymorphism may be a risk
      factor for late onset AD.

PMID- 9774780
TI  - Support for the possible locus on chromosome 4p16 for bipolar affective disorder.
AB  - Significant evidence for linkage between bipolar affective disorder and markers
      on chromosome 4p16 has been reported in Scottish families. Linkage analyses using
      16 DNA markers covering more than 50 cM from chromosome 4pter-4p12, including
      candidate genes encoding the dopamine D5 receptor and an adrenergic receptor
      (2C), were performed in two Danish families with bipolar affective disorder.
      Assuming homogeneity in the two families, the highest lod score found in the two
      point linkage analyses was 2.00 at 0.03 recombination fraction for D4S394, i.e.
      the marker which also was most significant in the original Scottish study.
      Simulation showed that such a lod score would only occur six out of 10,000 times
      with an unlinked marker. Though the present study thus replicates the Scottish
      findings according to the criteria suggested by Lander and Kruglyak, caution is
      warranted as the mode of inheritance which yielded the highest lod score in the
      two studies was different. Final proof of a disease locus in the Scottish and our
      study has to await the identification of a DNA sequence of functional
      significance for bipolar disorder.

PMID- 9774781
TI  - An association study of a functional polymorphism of the serotonin transporter
      gene with personality and psychiatric symptoms.
AB  - A functional polymorphism in the regulatory region of the serotonin transporter
      gene has been reported to be associated with anxiety-related personality traits.
      We attempted to replicate this finding in an association study involving 759
      Caucasians selected from the general Australian population. We found no
      associations with personality traits (including neuroticism, negative affect and
      behavioral inhibition), anxiety and depressive symptoms, or alcohol misuse.

PMID- 9774782
TI  - Linkage analysis of putative schizophrenia gene candidate regions on chromosomes
      3p, 5q, 6p, 8p, 20p and 22q in a population-based sampled Finnish family set.
AB  - During the past decade numerous studies have been published describing
      chromosomal regions potentially linked with schizophrenia. Unfortunately, none of
      these studies has been able to conclusively identify any specific gene that
      predisposes to schizophrenia. Typically evidence for linkage is seen on large
      chromosomal regions, as expected, containing tens or even hundreds of genes.
      Furthermore, attempts to replicate the findings have rarely been successful
      leaving a confusion about the existence of predisposing genes for schizophrenia
      in a particular region of the genome. We have carried out linkage analysis in a
      set of 62 pedigrees rising from a genetically isolated population of Finland with
      markers on six chromosomal regions earlier suggested to harbor predisposing genes
      for schizophrenia, namely 3p, 5q, 6p, 8p, 20p, and 22q. We were not able to find
      significant evidence for linkage on any of these chromosomal regions. However,
      some support for linkage was found on all studied chromosomal regions, except 3p.

PMID- 9774783
TI  - Active resistance of entomophagous rhabditid Heterorhabditis bacteriophora to
      insect immunity.
AB  - A specific extracellular proteinase, degrading selectively the cecropin-based
      defence system of insects, is secreted into the larval body during parasitism of
      the greater wax moth by the Heterorhabditis bacteriophora/Photorhabdus
      luminescens complex and by phase 1 of P. luminescens. The proteolytic digestion
      of insect inducible cecropin-like immune molecules was demonstrated by the
      disappearance of the Galleria mellonella cecropins and purified Hyalophora
      cecropin B peptide PAGE bands upon exposure to infected extracts, and a similar
      abrogation of antibacterial activity using an agar diffusion assay. Proteolytic
      activity of infected extracts produced by nematode/bacterial complex and phase 1
      variant of P. luminescens was shown to be correlated with cecropin-inhibitory
      activity, suggesting that this anti-cecropin agent may be responsible for the
      ability of bacteria to establish infection and the insecticidal nature of H.
      bacteriophora. Antibacterial activity of Galleria lysozyme and that of chicken
      egg-white lysozyme to which P. luminescens is insensitive, was unaffected by H.
      bacteriophora proteinase.

PMID- 9774784
TI  - Antibodies to sequences in a non-repeat region of Plasmodium falciparum antigen
      Pf155/RESA inhibit either cytoadherence or parasite growth in vitro.
AB  - Antibodies to a non-repeat region of the Plasmodium falciparum antigen Pf155/RESA
      were investigated for their capacity to inhibit parasite cytoadherence to
      melanoma cells and parasite growth in vitro. The activities of these antibodies
      were studied since the target region in Pf155/RESA includes a cytoadherence
      related motif also found in loop 3 and 7 of human erythrocyte band 3 protein.
      Overlapping multiple antigen peptides (MAPs) together spanning residues 199-220
      of Pf155/RESA were used to raise antibodies in rabbits. Analysis of the fine
      specificity of these antibodies revealed that antibodies raised against largely
      overlapping sequences displayed highly different specificity patterns. Similarly,
      striking differences were seen when analysing the biological effect of antibodies
      to these MAPs. Antibodies to the cytoadherence-related motif of Pf155/RESA, as
      well as antibodies raised against a MAP based on a corresponding band 3 motif,
      inhibited cytoadherence but not parasite growth. In contrast, antibodies to
      sequences adjacent to the Pf155/RESA cytoadherence motif inhibited parasite
      growth in vitro but had no effect on cytoadherence.

PMID- 9774785
TI  - Impaired thyroid function in murine toxoplasmosis.
AB  - A decline in serum thyroxine (T4) occurs in Nya: NYLAR female mice infected with
      Toxoplasma gondii. To ascertain whether the hypothyroxinaemia might be the result
      of primary thyroid dysfunction, 2 parameters of thyrofollicular cell function
      were monitored to determine (a) if the cell surface membrane receptors for
      thyroid-stimulating hormone (TSH) were operative, and (b) whether the cyclic
      adenosine monophosphate (cAMP)-dependent cascade of intracellular events leading
      to the release of T4 was responsive to exogenous cAMP. Our results indicated that
      both parameters were intact and functional in the infected-mouse thyrocytes.
      However, the elicited T4 responses were distinctly diminished in magnitude,
      reflecting a lack of readily available thyroidal T4 reserves. Because the
      continuing synthesis, storage, and release of T4 is dependent on the pulsatile
      stimulation of the thyroid by TSH, we suggest that the depletion of T4 reserves
      is likely due to perturbation of the pulsatile release of TSH from the pituitary,
      rather than to primary thyroid malfunction.

PMID- 9774786
TI  - Aetiology of thyroidal dysfunction in murine toxoplasmosis.
AB  - Mice infected with Toxoplasma gondii manifest a rapid decline in serum thyroxine
      (T4) levels. To locate the locus of the hypothyroxinaemia, the integrity of the
      pituitary-thyroid axis of infected mice was assessed by a thyrotropin-releasing
      hormone (TRH) assay. A rise in serum T4 after inoculation of TRH implies the
      release of thyrotropin (thyroid-stimulating hormone) from a functionally intact
      pituitary. Administration of a single, large-dose (1 microgram) bolus of TRH to
      infected mice induced a positive, although subnormal, T4 response. In contrast,
      when infected mice were pre-treated with a series of low-dose (5 ng) pulses of
      TRH prior to the bolus challenge, the T4 response was markedly enhanced. We
      suggest that the multiple inoculations of low-dose pulses of TRH 'primed' the
      pituitary (and secondarily the thyroid) and led to replenishment of their readily
      available hormone reserves and the heightened response to stimulation. These
      observations indicate that the locus of thyroid dysfunction is in the
      hypothalamus, not the pituitary or thyroid, and apparently involves impairment of
      the pulsatile release of TRH.

PMID- 9774787
TI  - A novel and simple colorimetric method for screening Giardia intestinalis and
      anti-giardial activity in vitro.
AB  - A new and simple colorimetric method has been developed for determining activity
      in vitro against Giardia intestinalis. The microtitre plate assay is based upon
      the nucleoside hydrolase activity released from G. intestinalis by lysis. Action
      of the nucleoside hydrolase on the substrate analogue, 4-nitrophenyl beta-D
      ribofuranoside (NPR), gives rise to a coloured product which may be determined
      directly by the change in absorbance. A number of other such nucleoside analogues
      can be similarly used, but NPR is the preferred substrate, since it gives high
      enzymic activity at a relatively low substrate concentration. The IC50 values
      determined using this method for the known anti-giardials metronidazole,
      tinidazole and furazolidone were consistent with previously published values. The
      method is simple, does not involve radioisotopes or complex instrumentation, and
      thus provides a convenient method for screening potential anti-giardial agents.

PMID- 9774788
TI  - Comparison of the intergenic spacers and 3' end regions of the large subunit
      (28S) ribosomal RNA gene from three species of Schistosoma.
AB  - The sequences for the entire intergenic spacer (IGS) and 3' end region of the
      large subunit (28S) ribosomal RNA gene are presented for Schistosoma
      intercalatum, S. haematobium and S. mansoni. The IGS was found to have at least 2
      size formats for S. intercalatum and S. haematobium and the region for all 3
      species contains numerous repeats and evidence of recombination. An A + T rich
      sequence found in S. intercalatum and S. haematobium is described and its
      possible function and origins are discussed. The amplification of this region by
      means of the polymerase chain reaction can be used to discriminate clearly
      between the 3 species involved in this study. The putative end of the 28S gene is
      identified.

PMID- 9774789
TI  - On the molecular taxonomy of Trypanosoma cruzi using riboprinting.
AB  - In order to investigate the molecular taxonomy within Trypanosoma cruzi, the
      ribosomal small subunit (18S) gene was amplified by polymerase chain reaction
      (PCR) from a selection of 21 stocks and 3 outgroup taxa. Amplification products
      were digested with 10 restriction enzymes; restriction fragments were separated
      by polyacrylamide gel electrophoresis and profiles were visualized by silver
      staining. Upon analysis of such riboprint profiles, an estimate of pairwise
      phenetic distance between stocks of T. cruzi was calculated. Upon principal
      coordinate analysis of this data matrix, a tendency towards a bi-polar grouping
      of stocks was observed. These 2 groups were predominantly either zymodeme 1
      stocks or zymodeme 2 stocks. The position of zymodeme 3 stocks remained
      intermediate between the 2 groups but did not form a coherent group by
      themselves. It would therefore appear premature to warrant division of T. cruzi
      into 2 discrete taxa or subspecies until the relationships of further zymodeme 3
      stocks are elucidated.

PMID- 9774790
TI  - Temperature gradient gel electrophoresis (TGGE) analysis of riboprints from
      Trypanosoma cruzi.
AB  - To test the homogeneity of 18S sequences within Trypanosoma cruzi, riboprint
      profiles were separated by temperature gradient gel electrophoresis (TGGE). Upon
      interpretation of melting curves of fragments within a riboprint profile, there
      appeared to be two 18S sequence types within each stock examined. Two similar
      types were also observed within outgroup taxa Trypanosoma conorhini, Trypanosoma
      rangeli and Leishmania braziliensis. From DNA hybridization studies, these
      fragments were shown to have homology to the 18S V1 region. There are therefore
      two 18S V1 regions, differing in sequence, present in all taxa examined. When
      only a single 18S sequence is used to represent each taxa for phylogenetic
      inference, comparisons may be between paralogous and not orthologous copies of
      this region, such that, inferred relationships may merely reflect a gene history.
      This seriously questions the current molecular phylogeny of these protozoa using
      18S data.

PMID- 9774791
TI  - Theileria lestoquardi--maturation and quantification in Hyalomma anatolicum
      anatolicum ticks.
AB  - The maturation and quantification of Theileria lestoquardi (T. hirci) parasites
      in unfed and partially fed adult Hyalomma anatolicum anatolicum ticks was studied
      using (1) methyl green pyronin (MGP) staining of salivary glands, (2) in vitro
      infection of peripheral blood mononuclear cells (PBM) with parasites harvested
      from infected ticks and (3) a semi-quantitative polymerase chain reaction (PCR).
      With MGP staining the greatest infection rate was seen in unfed ticks. Feeding
      resulted in a gradual reduction in the number of infected acini with a
      concomitant increase in the maturity of the parasites. In vitro infection of
      sheep PBM with titrated group-up tick supernate (GUTS) demonstrated that
      infectivity peaked between 2 and 4 days of tick feeding whereas GUTS prepared
      from unfed ticks was not infective. The polymerase chain reaction (PCR) was both
      sensitive and specific, detecting T. lestoquardi DNA in unfed and partially fed
      ticks, with a maximum sensitivity of 0.022 infected acinus/tick in 2-day fed
      ticks, though it gave no indication of the infectivity of the parasite.

PMID- 9774792
TI  - Juvenile female Litomosoides sigmodontis produce an excretory/secretory antigen
      (Juv-p120) highly modified with dimethylaminoethanol.
AB  - A 120 kDa antigen produced by juvenile female Litomosoides sigmodontis (Juv-p120)
      was isolated and purified. The amino acid composition of the molecule was
      determined. Juv-p120 was shown to be highly modified with N,N-dimethyl
      aminoethanol (28.4 mol%). Treatment of Juv-p120 with potassium hydroxide (beta
      elimination) or with sodium m-periodate leads to the destruction of epitopes
      recognized by antibodies immune affinity-purified with isolated Juv-p120.
      Juvenile L. sigmodontis were shown to release Juv-p120 into the pleural cavity of
      infected Mastomys coucha before the onset of patency.

PMID- 9774793
TI  - No interspecific covariation in intensities of macroparasites of reindeer,
      Rangifer tarandus (L.).
AB  - The macroparasites Cephenemyia trompe (Modeer) and Hypoderma (= Oedemagena)
      tarandi (L.) (Diptera: Oestridae), Linguatula arctica Riley, Haugerud and Nilssen
      (Pentastomida: Linguatulidae), Elaphostrongylus rangiferi Mitskevich (Nematoda:
      Protostrongylidae), and abomasal nematodes (Nematoda: Trichostrongylidae) were
      sampled in semidomestic reindeer calves (Rangifer tarandus (L.)) (ca. 8 months of
      age) in northern Norway in 1988 (n = 160) and 1989 (n = 191). Each parasite
      showed an aggregated (clumped) distribution among the hosts and fitted the
      negative binomial distribution. Analyses of interspecific associations in
      intensities showed that there was no consistent covariation among the parasites
      apart from a weak correlation (Kendall's tau 0.104, P = 0.007) between the 2
      oestrids C. trompe and H. tarandi. This lack of covariation reveals that the
      parasites were distributed independently of each other, and suggests that innate
      host resistance is not a dominant factor that has a significant simultaneous
      effect on all parasites. The aggregated distribution of each parasite species is
      hypothesized to be caused by (1) random events and heterogeneities in host
      behaviour that create unequal transmission (exposure) rates, or (2) by
      heterogeneities in parasite specific immunocompetence among host individuals.
      Factors in hypothesis (1) are probably the most important at low transmission
      rates.

PMID- 9774794
TI  - The NADPH-diaphorase staining reaction in relation to the aminergic and
      peptidergic nervous system and the musculature of adult Diphyllobothrium
      dentriticum.
AB  - A new category of signalling molecules--transmitter gases--has appeared. Nitric
      oxide (NO) is generated by nitric oxide synthase (NOS) and diffuses as a short
      lived transcellular messenger through the plasma membrane. NADPH-diaphorase
      (NADPH-d) is a marker enzyme for NO-producing neurons. In this study the pattern
      of NADPH-d stained neurons in Diphyllobothrium dendriticum is described and
      compared to the pattern of aminergic and peptidergic neuronal elements and to
      that of the musculature stained with TRITC-labelled phalloidin. NADPH-d staining
      was observed in neurons in the bilobed brain and along the 2 main nerve cords and
      in nerve fibres close to the body musculature and the musculature of the
      reproductive ducts, the walls of the testicular follicles and in sensory endings
      in the tegument. The NADPH-d staining reaction and the 5-HT or FMRFamide
      immunoreactivities occur in separate sets of neurons.

PMID- 9774795
TI  - Brain functions and psychiatric disorders. A clinical view.
AB  - Psychiatric disorders are viewed as brain disorders affecting five circuits of
      the brain: the brainstem, the hypothalamus, the motor striatum, the limbic system
      (ventral striatum), and the neocortex. This five-circuit model combines
      neuroscientific, psychopharmacologic, evolutionary, introspective, and behavioral
      data. The article presents a broad speculative overview of some brain functions
      and dysfunctions relevant for clinicians.

PMID- 9774796
TI  - Unusual diagnoses among violent patients.
AB  - Several medical disorders rarely cause violent behavior. When they do so, it is
      dramatic because the violence and other bizarre behaviors are not in keeping with
      the premorbid picture of the individual. Often, medical and neurologic symptoms
      are present, but occasionally psychiatric symptoms may present alone with the
      aggression and violence, which points out the importance of complete medical
      psychiatric evaluations of patients who present with recent histories of violent
      behavior. Most violence involves "horses," but the rare "zebras" should be kept
      in mind because they are often treatable.

PMID- 9774797
TI  - Premenstrual syndrome.
AB  - The advances in the careful screening and diagnosis of women with PMS has led to
      the ability to conduct epidemiologic, etiologic, and treatment studies in well
      defined samples of women. Prospective symptom charting, scoring methods, and
      careful clinical psychiatric and medical evaluation are necessary to rule out
      concurrent psychiatric and medical disorders. Studies of women with PMDD have
      suggested several promising pharmacologic treatment options. Whether these
      treatment options are also successful for women with milder premenstrual
      symptoms, with premenstrual exacerbation of underlying conditions, or with
      premenstrual symptoms superimposed on underlying psychiatric and medical
      conditions remains to be studied. Treatment of premenstrual symptoms by
      pharmacologic or nonpharmacologic methods may be unsuccessful if the underlying
      psychiatric or medical condition is not addressed first.

PMID- 9774798
TI  - Sleep disorders presenting as psychiatric disorders.
AB  - In summary, disordered sleep can present in a complex and atypical fashion in
      which the primary sleep-related component may not be immediately apparent. A high
      index of suspicion serves the clinician well in these cases. A careful and
      systematic evaluation of sleep often proves to be rewarding in terms of
      diagnostic accuracy and improved treatment outcome.

PMID- 9774799
TI  - Minor head trauma.
AB  - This article reviews the persisting difficulty and the importance of the
      diagnosis of minor head trauma. The diagnosis has been complicated by pervasive
      disagreement regarding diagnostic criteria. This is primarily a result of the
      fact that evidence for actual injury is hard to obtain in minor cases because
      most symptoms tend to be subjective and have high base rates in the normal,
      uninjured population. At the same time, the diagnostic decision has important
      implications for patients in terms of treatment, expectancy for future function
      and lifestyle, and compensation for injuries. Decision theory leads us to the
      awareness of diagnostic errors. In addition to correct determination, the
      clinician can make an error of not diagnosing an injury when it has in fact
      occurred or making a positive diagnosis where there is no injury. The optimal
      strategy is to set the cutoff at the midpoint of these two error probabilities.
      The clinician may be willing to make one error rather than the other depending on
      the cost and bias involved. The second error is more likely to be made when the
      clinician stands as a strong advocate for the patient and willing to provide any
      help necessary to encourage treatment, give patients a rationale for
      understanding their symptoms, and help them obtain compensation for injuries.
      This can also lead to significant overdiagnosis of injury. The first error is
      more likely to be made when the clinician recognizes the potential for increasing
      costs to the health-care industry, the court system, and increasing personal
      injury claims. He or she may also recognize the vulnerability to the risk for
      symptom invalidity, the perpetuation of patient symptoms through suggestion, and
      the need for a biologic explanation for life stressors and preexisting emotional
      and personality constraints. It can be argued that the most objective diagnostic
      opinion, uninfluenced by the above biases, should ultimately be in the best
      interest of the patient, the clinician, legal consultants, and society. Based on
      the findings in this chapter, at least four symptom constellations can be
      identified. These have differing probabilities for residual symptoms of minor
      head trauma and include the following: 1. These patients' symptoms clearly meet
      the criteria from Table 2. This includes several findings from 1 to 10 of Table
      1, together with abnormal neuropsychologic testing on the AIR, General
      Neuropsychological Deficit Scale, or other indicators of diminished cortical
      integrity. This group of patients shows a very strong probability of having
      experienced a brain injury and for showing residual symptoms of minor head
      trauma. 2. These patients have experienced concussional symptoms (e.g., headache,
      mild confusion, and balance and visual symptoms) that were documented at the time
      of injury but sustained no or brief (< 15 seconds) LOC or PTA and, therefore, do
      not qualify for the diagnosis in Table 2. They may still have several symptoms
      from Table 1, including objective findings from neuroscanning and variable
      neuropsychologic testing, especially in measures of attention and delayed recall.
      This group also shows a high probability for residual, unresolved concussional,
      and related symptoms. 3. These patients may have shown evidence of concussional
      symptoms at the time of injury, with no or brief LOC, PTA, or other symptoms from
      Table 1 (1-10). They continue to show persistent symptoms after 6 months to 1
      year. With this group, there is a strong probability that emotional, motivational
      and premorbid personality factors are either causing or supporting these residual
      symptoms. 4. In these patients, clearly identifiable postconcussive symptoms at
      the time of injury are not easy to identify, and perhaps headache is the only
      reported symptom. There was no LOC or PTA, and virtually none of symptoms 1 to 10
      in Table 1 are observed. These patients show strong evidence of symptom
      invalidity on MMPI-2 or other measures, and marked somatoform, depression, anx

PMID- 9774800
TI  - Seizure disorders presenting with psychiatric symptomatology.
AB  - Seizure disorders can be mistaken for psychiatric disorders and, the two have a
      number of poorly understood interrelations. Disruptions of consciousness, motor
      activity, hallucinations, and abrupt mood and anxiety changes can all be seizure
      manifestations caused by cortical neuronal discharges. This article presents the
      classification and proposed psychopathology of seizure disorders. It then reviews
      the psychiatric conditions that frequently mimic elements of such seizure
      disorders, giving hints that will allow the clinician to correctly identify
      seizures that are creating psychiatric presentations. Finally, this article makes
      clear the situations in which anticonvulsant medications may be of value when
      nothing else seems to be working.

PMID- 9774801
TI  - The dissociative disorders. Rarely considered and underdiagnosed.
AB  - A wide variety of dissociative disorders, including dissociative amnesia,
      dissociative fugue, depersonalization disorder, dissociative identity disorder,
      and various forms of dissociative disorder not otherwise specified. In many
      instances, these disorders are either underdiagnosed or misdiagnosed secondary to
      the clinician's mistaken belief that dissociative disorders are rare. Recent
      research shows that dissociative disorders may comprise 5% to 10% of psychiatric
      populations. This article reviews the epidemiology and clinical symptomatology of
      these disorders. In addition, various screening and diagnostic instruments, such
      as the DES, Structured Clinical Interview for Dissociative Disorders, and MMPI,
      are discussed.

PMID- 9774802
TI  - Pseudoseizures.
AB  - Pseudoseizures represent the opposite end of the spectrum from seizures that
      mimic psychiatric disorders: they are paroxysmal changes in behavior that
      resemble epileptic seizures, but which are without organic cause and expected EEG
      changes. Accurately distinguishing pseudoseizures from epilepsy and other
      illnesses is difficult because of the breadth and overlap of symptoms seen in
      each condition and because of the frequent co-occurrence of pseudoseizures and
      epilepsy. This article summarizes the various neurological and psychiatric clues
      that help the clinician identify this form of psychiatric presentation, whether
      it represents, for example, a conversion disorder, a dissociative disorder, or a
      panic disorder.

PMID- 9774803
TI  - Missed diagnoses and misdiagnoses of environmental toxicant exposure. The
      psychiatry of toxic exposure and multiple chemical sensitivity.
AB  - Toxins such as carbon monoxide, lead, and mercury that present occasionally with
      primarily psychiatric symptoms can pose some of the most difficult diagnoses.
      This article reviews the clues that can allow the diagnostician to identify the
      role of one of these substances. Equally important, the article discusses the
      contentious issues that surround the phenomen known as multiple chemical
      sensitivity. Viewed primarily as a functional illness, often with legal
      overtones, this putative disorder is critically reviewed to see if it meets the
      same demanding standard of validity that is found in the psychiatric symptoms
      associated with other toxic disorders. Although questioning the strict medical
      origin of medical chemical sensitivity, the article outlines some treatment hints
      that may helpful in the management of this difficult group of patients.

PMID- 9774804
TI  - Chronic fatigue syndrome and fibromyalgia. Dilemmas in diagnosis and clinical
      management.
AB  - There has been a resurgence of interest in recent years in both chronic fatigue
      syndrome and fibromyalgia. These perplexing and common clinical conditions are a
      source of significant patient morbidity and frame one of the more enduring
      dilemmas of contemporary Western medical thought, namely the ambiguous interface
      between mind and body. In this article, the current definitions are reviewed, and
      a framework for an emerging psychobiological model of these syndromes is
      presented. These issues are synthesized into a pragmatic approach to clinical
      management.

PMID- 9774805
TI  - The underdiagnosis of neuropsychiatric Lyme disease in children and adults.
AB  - Lyme Disease has been called "The New Great Imitator," a replacement for that old
      "great imitator" neurosyphilis. This article reviews the numerous psychiatric and
      neurologic presentations found in adults and children. It then reviews the
      features of Lyme Disease, which makes it almost uniquely hard to diagnose,
      including the complexity and unreliability of serologic tests. Clinical examples
      follow that illustrate those presentations of this disease that mimic attention
      deficit hyperactivity disorder (ADHD), depression, and multiple sclerosis.

PMID- 9774806
TI  - Missed diagnoses in consultation liaison psychiatry.
AB  - In this article, an experienced consultation liaison psychiatrist presents
      several cases in detail that illustrate the wide range and complex natures of
      psychiatric patients seen on the medical and surgery floors. The cases presented
      appear as they would to the psychiatrist consulting within the hospital and
      represent a challenging test of the clinician's diagnostic skills, an experience
      encountered daily by the consultation liaison psychiatrist.

PMID- 9774807
TI  - [Phenomenology of motor crisis in non-epileptic patients with psychogenic
      crises].
AB  - INTRODUCTION: Recognition of different ictal motor patterns in psychogenic
      seizures may be useful in terms of differentiation from epileptic seizures and
      may also improve understanding the underlying psychopathology. OBJECTIVE: To
      outline recognizable ictal motor patterns that may help to distinguish
      psychogenic motor seizures from epileptic convulsive episodes. PATIENTS AND
      METHODS: Chart review from 54 patients with motor psychogenic seizures and no
      clinical or EEG evidence of concomitant epilepsy. RESULTS: Only 5 patients (9.2%)
      experienced more than one ictal motor pattern along their illness. Categorization
      into four subtypes according to ictal motor behaviour was possible in all other
      patients: psychogenic seizures with flaccid unconsciousness (32.6%),
      combativeness (32.6%), a hypermobile subtype (24.4%) as defined by the presence
      of intentional movements or slow rhythmic oscillations of a segment or the entire
      body, and rigidity (10.2%). CONCLUSIONS: Many psychogenic motor seizures
      consistently present with recognizable motor phenomena which may be readily
      identified providing the availability of a reliable witness. Psychogenic seizures
      as presented spontaneously in a general neurology setting may differ from those
      reported in biased referrals to video-EEG laboratories. Recognition of
      characteristic patterns may help differentiation from tonic-clonic convulsions,
      avoid unnecessary examinations, and may provide insights into their underlying
      psychopathological mechanisms.

PMID- 9774808
TI  - [Effect of biscuits fortified with haem iron on the intellectual status of pre
      school children].
AB  - INTRODUCTION: In undeveloped countries such as Peru there is a high prevalence of
      ferropenic anemia. In addition, iron deficiency produces cognitive alterations
      that could be corrected by iron treatment. OBJECTIVE: To evaluate the effect of
      administration of heme iron-fortified cookies on the intellectual status of
      preschool children. PATIENTS AND METHODS: Using the Goodenough-Harris Test (GHT)
      and Wechsler Preschool and Primary Scale of Intelligence (WPPSI) we studied the
      intellectual status of 53 children who received heme iron-fortified cookies for 6
      8 weeks and 55 controls without fortification, in 2 occasions (before and after
      intervention). RESULTS: We observed a significantly higher improvement in
      children who received iron respect to controls for GHT score (p < 0.001), WPPSI
      score (p < 0.05), WPPSI attention-concentration subscale (p < 0.01) and WPPSI
      pure attention subscale (p < 0.05). CONCLUSION: Administration of heme iron
      fortified cookies may improve the intellectual performance of low-income
      preschool children.

PMID- 9774809
TI  - [Use of antiparkinsonian agents in Castilla-La Mancha. Estimate of prevalence of
      Parkinson disease].
AB  - INTRODUCTION: Research concerning the prevalence of Parkinson disease (PD) are
      scarce; in addition with different methodologies. Therefore it is not possible to
      determine its true impact on public health in Castilla-La Mancha (CLM), Spain.
      OBJECTIVE: Determine the prevalence of PD in CLM (332.0 and 332.1 of the ICD-9th
      revision) by the consumption of antiparkinsonian drugs. PATIENTS AND METHODS:
      Calculating the daily defined doses (DDD) per 100,000 inhabitants (10(5)) for
      each of the prescribed antiparkinsonian drugs (Therapeutic Group, N04A), during
      1994-1996 for each of the province of CLM. The data from prescriptions have been
      obtained from the Pharmaceutical Service of the Health and Consume Ministry of
      Spain, which cover 100% of the population. RESULTS: The DDD determination's of L
      Dopa per 10(5) inhabitants, a prevalence of 270.24 (IC 95%: 239.2-304.7) is
      estimated for the whole population. The consumption of L-Dopa by provinces and
      years (1994-1996) allows to know the distribution of PD in CLM. CONCLUSIONS: The
      numbers obtained place to CLM in a middle-high prevalence; although
      methodological differences do not allow definitive conclusions.

PMID- 9774810
TI  - [Non-cognitive aspects of dementia].
AB  - OBJECTIVE: To observe the frequency of various psychiatric disorders (depressive
      disorders, anxiety state and paraphrenic-paranoid disorders). PATIENTS AND
      METHODS: This study includes the 'cases' of dementia detected in an
      epidemiological field study done door-to-door, double phased and including non
      institutionalized persons aged over 69 years in a rural area. All diagnoses were
      done by CAMDEX and on these criteria. RESULTS: Depressive disorder was diagnosed
      in 26.5% studied, paraphrenic or paranoid disorder in 14% and anxiety state in
      6.5%. Depression and paraphrenic-paranoid disorder were not associated with the
      severity of the dementia, whilst anxiety state was more commonly seen in mild
      dementia. Paraphrenic-paranoid disorders were commoner in women than in men.
      CONCLUSION: The considerable prevalence of other psychiatric diagnoses in persons
      with dementia shows that non-cognitive symptoms are common in these patients.

PMID- 9774812
TI  - [Electroclinical and neuroimaging studies in epilepsy].
AB  - INTRODUCTION AND MATERIAL: During 54 months, we have studied the electro-clinical
      and neuroimaging features in outpatients with active epilepsy. Each patient was
      interviewed for one of us. Then, we have reviewed the medical records about both
      the clinical featuring. EEG and neuroimaging (NI) studies and seizures frequency
      (SF) outcome. Differences in crude proportions were assessed by chi 2 test for
      independence by 2 x 2 tables. RESULTS AND CONCLUSIONS: It has been 207 patients
      with 49 +/- 19.6 years of mean age at review. Partial seizures was significantly
      related with both a higher SF at onset and politherapy. Also, with a focal EEG
      distribution but only in case of complex partial seizures. Abnormal NI was
      significantly more frequent in oldest patients. A greater proportion of patients
      were in politherapy in four situation: SF at onset > 1 by day, a focal EEG
      distribution, duration of epilepsy longer than 20 years and age of onset lesser
      than 60 years. A 37.2% was seizures-free in the last year and in 34% the SF was
      improved a 50% or more from the beginning. A significantly greater proportion of
      patients was following with seizures in four cases: when the SF at onset has been
      > or = 1 by day, being partial seizures, women and having politherapy.

PMID- 9774811
TI  - [The prognosis of epilepsy in children with generalized spikes and wave disc
      charges in electroencephalographic recording].
AB  - INTRODUCTION: Epilepsy is a chronic disorder. The prognosis of one particular
      subtype, that of children with generalized spike and wave discharges (P-O) on the
      electroencephalogram (EEG), is unknown. OBJECTIVE: To determine the prognosis of
      children with epilepsy with P-O on EEG and the factors which affect this.
      PATIENTS AND METHODS: All EEGs done over ten years (39,322) were reviewed, and
      the epileptic patients under 14 years old identified. Absence and recurrence of
      crises were evaluated and the factors influencing them analyzed. Minimum
      significance was p < 0.05. The chi square test, Student's t test and Kaplan-Meier
      method were used. Logistic regression models were devised. RESULTS: Of the
      children studied, 78% became crisis-free. After monovariant and multivariant
      analysis the only conditions which fitted the regression models were: abnormal
      pregnancy; West syndrome or learning difficulties; having certain types of
      crises, myoclonic, clonic-tonic, partial simple or complex crises; a normal EEG
      with hypsarrhythmia, slow or fast P-O and requiring multiple medication. When
      medication ceased, 31.4% had recurrence of the episodes. On monovariant and
      multivariant analysis, protective factors were absence of attacks and risk
      factors were a family history of epilepsy or an EEG with rapid P-O. CONCLUSIONS:
      The overall prognosis for epileptic children with P-O is good. There are factors
      which improve or worsen the pronosis, but these cannot be modified.

PMID- 9774813
TI  - [Etiological factors of epilepsy].
AB  - INTRODUCTION: The epilepsies are one of the main reasons for consultation and
      hospital admission in neurology. They may be caused by multiple factors.
      OBJECTIVES: To determine the types of epilepsy, their aetiology and the value of
      a clinical history in diagnosis of their cause. PATIENTS AND METHODS: We studied
      96 epileptic patients aged over 15 years in the epilepsy clinic of the Hospital
      Dr. Carlos J. Finlay in La Habana, Cuba. On a questionnaire we recorded: family
      history, pre-, peri- and postnatal histories, clinical features of the crises and
      physical exploration. All had inter-ictal electroencephalograms, 62 had cranial
      CTs, 36 had MR studies and 8 had both types of imaging studies. We excluded acute
      metabolic disorders and cerebral tumours. RESULTS: There was a predominance of
      persons aged between 26 and 35 (78%) and 59.37% were men. Symptomatic epilepsy
      was seen in 51.4%, in 38.54% this was cryptogenic and in 10.41% idiopathic.
      Perinatal damage was present in 20.8%, head injury in 11.4%, febrile convulsion
      in 10.4%, meningoencephalitis in 8.3% and cardiovascular disease in 4.1%.
      CONCLUSIONS: The international classification of epilepsy permits our patients to
      be divided into groups. In most of them aetiological factors were detected after
      an interview and medical exploration.

PMID- 9774814
TI  - [Outpatient care of patients with Parkinson disease].
AB  - INTRODUCTION: Some neurology clinics have been set up in specialist centres
      during the last ten years and their activities described. The group of patients
      with Parkinson's disease attended in the clinics of specialist centres have the
      distinguishing feature of where they are treated, which makes them different to
      other groups with the same disorder. OBJECTIVE: In this article we describe the
      general data of neurological attention for patients with Parkinson's disease,
      seen in two clinics belonging to specialist centres. PATIENTS AND METHODS: This
      article is based on records of patients made by neurologists of two structured
      centres in Hospital La Fe. RESULTS: In a period of 18 months 228 patients with
      Parkinson's disease were recorded out of a total case register of 5,101. Patients
      with Parkinson's disease made up between 4% and 5% of the patients attending the
      clinic. Between 30% and 50% of the patients seen in these clinics were evaluated
      only once during the period recorded. CONCLUSIONS: There seems to be a large
      number of cases recorded and these represent 70% of the estimated number of cases
      in the area. It seems that some patients do not keep in contact with the
      neurologist. Differences in function noted in clinics of specialist centres,
      between each other and compared with hospitals, are due to specific organizations
      and structures.

PMID- 9774815
TI  - [Idiopathic intracranial hypertension in childhood].
AB  - INTRODUCTION: We present the cases of idiopathic, intracranial hypertension (HII)
      in children studied in our hospital over the past 15 years (14 cases), reviewing
      the clinical features, complementary tests, associated causes, treatment and
      evolution. PATIENTS AND METHODS: Diagnosis of HII was based on a modification of
      Ahlskog's criteria (1982) (the child was sedated to avoid increased cranial
      pressure due to crying): no focal signs, CSF pressure greater than 200 mm of H2O,
      normal composition of CSF and normal neuro-imaging findings. Two groups were
      established according to age. The first group included those under 24 months old
      and the second group those over 24 months. Differences were seen in the
      presenting, symptoms, neurological examination and treatment. RESULTS: In the
      first group the cause of consultation was irritability and a bulging fontanelle.
      They recovered after simply restricting fluids and treating the associated cause.
      In the second group, consultation was for headache and vomiting, and sometimes
      diplopia also. Recovery was satisfactory (except in one case) when
      corticosteroids were added to the above treatment. The complementary tests
      carried out depended on the clinical history, general and neurological
      examination and associated cause (MR, vitamin A levels, nutritional index, etc.).
      A possible aetiological relationship was found in 75% of cases. CONCLUSIONS: We
      emphasize the favourable course and good prognosis of HII in infants as compared
      to adults.

PMID- 9774816
TI  - [Cross-sectional multicenter study of outpatient neurological care in the
      autonomous region of Valencia. Commission on Analysis of Quality of the
      Neurological Society of Valencia].
AB  - INTRODUCTION: Studies of the use of resources is a method recommended for the
      determination of health care requirements in order to improve planning for this.
      OBJECTIVE: To analyze outpatient neurological care in the Autonomous Region of
      Valencia (CR). PATIENTS AND METHODS: A transverse multicentric study was done in
      different Neurology Clinics in the CV. For three days, chosen randomly, forms
      were filled in. RESULTS: Twenty neurologists participated. Analysis was done of
      954 consultations. In 30% of these cases the neurologist was satisfied and in 30%
      he was not. Consultation took 9.5% more time than anticipated. Urgent unscheduled
      consultations made up 8.6%. Women made up 52% and were of an average age of 52
      years. Delay was 29 days. Primary care services referred 42% of the patients. The
      commonest diagnoses were: cerebral infarct, migraine and parkinsonism. The
      conditions referred from Primary Care Services were similar to those from non
      neurological specialists. First visits took 17.6 minutes and following visits
      11.7 minutes. The most usual 'destination' was follow-up (75.2%), followed by AP
      (24%). CONCLUSIONS: Neurological care in the Neurology Clinics of the CV is
      easily accessible and of good quality. However, it is overloaded by the large
      demand, due to ambiguity of the health care system available. The different
      degrees of professional satisfaction felt by neurologists are probably due to the
      quality of health care available to patients depending on where they live and the
      type of centre they attend.

PMID- 9774817
TI  - [The role of PET-FDG in questionable diagnosis of relapse in the presence of
      radionecrosis of brain tumors].
AB  - INTRODUCTION: Although CT and MR are sensitive techniques for the detection of
      cerebral tumours, both have limitations in distinguishing between tumour relapse
      (TR) and post-treatment radionecrosis (RN). PATIENTS AND METHODS: In this study
      we have determined the usefulness of metabolic imaging with PET-FDG in such
      situations. We assessed 70 patients with CNS tumours (22 low grade astrocytomas,
      25 high grade astrocytomas, 3 oligodendrogliomas, 13 metastatic tumours and 7
      other tumours. All had been treated with radiotherapy and other treatments such
      as radiosurgery, chemotherapy or different types of surgery, and presented
      clinical pictures which made it necessary to decide the differential diagnosis of
      relapse or radionecrosis. RESULTS: In the PET-FDG study visual and
      semiquantitative analysis was done by SUV (Standardized Update Value).
      Confirmation of the findings was obtained in 44 cases (24 TR and 20 RN). MR was
      doubtful or inconclusive in most cases, whilst with PET correct diagnosis was
      made in all cases. CONCLUSIONS: Metabolic imaging with PET-FGD is better than
      anatomostructural imaging techniques for differential diagnosis between tumour
      relapse and radionecrosis in CNS tumours which have been treated. Prospective
      studies are necessary for evaluation of SUV as a factor for prognosis of
      survival.

PMID- 9774818
TI  - [Activity and costs of diagnosis-related groups (DRG) of neurological services at
      the Virgen de las Nieves Hospital of Granada].
AB  - INTRODUCTION: The influence on health costs of variations in the clinical
      practice of doctors makes it necessary for them to be involved in the
      administration of resources so as to increase the efficacy, effectiveness and
      efficiency of clinical units. OBJECTIVES: To analyze the activity of the
      Neurology Department of the Virgen de las Nieves Hospital of Granada and to
      determine its costs per GRD. PATIENTS AND METHODS: Activity during 1996 was
      compared with that of the previous year and with a standard using measurements of
      cases, efficiency in administration of beds, quality of data and quality of care.
      The GRD costs of the service were found. RESULTS: Ninety percent of the
      discharges were grouped in 20 GRD, and GRD 014 and 015 represented 44% of the
      productivity. Complexity of the cases was 5% more than in 1995, similar to that
      of Rule IV [20]. Extreme cases led to a third of all admissions. Mortality was
      less than expected (3.13%). Hospital stays made up 82% of the total cost. The
      cost of one stay in hospital was 463.686 pesetas. CONCLUSIONS: It is essential to
      improve the structure and procedures related to hospital care of patients with
      cerebral vacular pathology. Those with uncomplicated conditions should be
      attended as outpatients or in smaller hospitals. The GRD costs obtained are not
      comparable to those of other authors. Hospital activity should be measured
      homogeneously and use should be made of analytical accounting systems with common
      operators and standardized applications so as to obtain reliable, comparable
      data.

PMID- 9774819
TI  - [Western type cerebro-muscular dystrophy and congenital merosin deficiency
      muscular dystrophy: two terms for the same disorder].
AB  - INTRODUCTION: Congenital muscular dystrophies (CMD) are a clinically
      heterogeneous group of muscular disorders characterized by hypotonia, muscle
      weakness and early or congenital joint contractures. Electromyography reveals a
      myopathic pattern, creatine-kinase (CK) may be moderately elevated and muscle
      biopsy shows pathological changes consistent with a dystrophic process.
      OBJECTIVE: Report the cases of two brothers with 'Occidental type cerebro
      muscular dystrophy' versus 'merosin-deficient CMD'. PATIENTS AND METHODS: Two
      children, a boy and a girl, of a first consanguineous parents. In the first case,
      the diagnosis of Occidental type cerebro-muscular dystrophy was made in 1983, at
      the age of 4 years, according to clinical, biochemical, electromyographic,
      pathological and neuroradiological data. In the second case, the diagnosis of
      merosindeficient form of CMD was made with the same criteria and with
      immunohistochemistry and Western blot techniques in 1997, when she was 6 months
      old. CONCLUSION: Occidental type cerebro-muscular dystrophy, described 13 years
      ago by one member of our group, corresponds with merosin-deficient form of CMD.

PMID- 9774820
TI  - [Differential cognitive profiles of fronto-temporal dementia and Alzheimer's
      disease].
AB  - INTRODUCTION AND OBJECTIVE: When the clinical picture consists of prominent
      cognitive impairments (e.g. amnesia) with relatively mild behavioral symptoms, it
      can be very difficult to distinguish frontal lobe dementia (FLD) from Alzheimer
      disease (AD). However, these conditions may have distinct cognitive profiles that
      could be detected by means of neuropsychological testing. The objective was to
      examine the early differential cognitive feature between FLD and AD. PATIENTS AND
      METHODS: Twelve patients with FLD, 20 patients with AD, and 20 normal subjects
      matched for age and educational level were evaluated with the Folstein Mini
      Mental State Examination, the Signoret Memory Battery, the Boston Naming Test,
      Verbal Fluency (FAS), the Wechsler Adult Intelligence Scale, and the Trail Making
      Test. The FLD patients met the Lund and Manchester criteria, and the AD patients
      met the National Institute of Neurological Disorders and Stroke-Alzheimer Disease
      and Related Disorders Association (NINDS-ADRDA) criteria for clinically probable
      AD. RESULTS: FLD and AD patients were matched for the severity of dementia using
      the Global Deterioration Scale (3.8 +/- 0.3 versus 3.9 +/- 0.5 respectively).
      Mean Z scores were calculated in order to facilitate the comparison between the
      neuropsychological profiles obtained. FLD patients scored significantly better
      than AD patients in memory test, calculation, visuospatial abilities, and the
      naming test. AD patients performed better on executive tasks. CONCLUSION: These
      findings suggest that neuropsychological examination may be useful in
      differential diagnosis between FLD and AD

PMID- 9774821
TI  - [Therapeutic failure, treatment and non-treatment of childhood epilepsy].
AB  - INTRODUCTION: The classification of epileptic syndromes defines the prognosis and
      offers some orientation about treatment in childhood epilepsy. OBJECTIVE: To
      study the medical therapy according to epileptic syndromes in the everyday
      practice of a hospital based outpatient neuropediatric clinic. METHODS: Survey of
      the database using an algorithm to define therapeutic failure, treatment and
      spontaneous evolution, according to syndrome and drug, of all epileptic patients
      attended at the clinic during 1966. RESULTS: 465 patients with: monotherapy 38%,
      politherapy 20%, therapeutic success (follow-up after drug discontinuation) 21%,
      spontaneous evolution 22% (54% of partial idiopathic epilepsies). Most used
      antiepileptic drugs (VPA > CBZ > VGB > CLB > PB > PHT > LTG > ESM > PRM > GBT)
      are those with lowest failure rate and highest percentage of patients on
      monotherapy. Percentages of monotherapy in treated patients and of previous
      failure out of total number of patients are: idiopathic partial epilepsies: 85%
      and 10%; remote symptomatic partial: 58% and 43%; cryptogenic partial: 53% and
      50%; idiopathic generalized: 83% and 25%; symptomatic-cryptogenic generalized:
      34% and 63%; undetermined: 45% and 43%. CONCLUSIONS: Screening of the database
      serves as a quality control but the use of an algorithm offers only an
      approximation to reality. In idiopathic partial epilepsy treatment can be avoided
      in half of the patients and failure is lowest for VPA and CBZ. In idiopathic
      generalized epilepsies VPA predominance is almost absolute with a very low
      failure rate. In all other epileptic syndromes the therapeutic failure rate is
      about 50% regardless of drug, except for VPA which shows a moderately better
      outcome.

PMID- 9774822
TI  - [Hospital mortality in ischemia: influence of two vascular risk factors].
AB  - INTRODUCTION: Acute cerebrovascular disease is a serious neurological problem.
      Mortality is between 6% and 30%. Most studies are in agreement that advanced age,
      type of ictus, size of lesion and clinical deterioration are factors determining
      mortality. However, its relationship to vascular risk factors is not completely
      clear. OBJECTIVE: To analyze the repercussion of different vascular risk factors
      on mortality during the acute phase of ictus. PATIENTS AND METHODS: We studied
      all patients with ictus admitted to the Servicio de Neurologia of the Hospital
      Xeral de Galicia de Santiago de Compostela over a period of 3 years (n = 915). We
      recorded vascular risk factors and analyzed the causes of mortality whilst in
      hospital. RESULTS: Hospital mortality due to ictus was 16.8%. Mortality was 14.5%
      in cerebral infarct, 23.2% in intracerebral haemorrhage and 19.4% in subarachnoid
      haemorrhage. A total of 20.8% of the patients died of neurological causes, 24.7%
      of vascular causes, 26% due to infection and of uncertain causes in the remaining
      28.6%. There was a neurological cause of death in 46.1% of the patients with
      subarachnoid haemorrhage, 25.5% with intracerebral haemorrhage and 14.8% with
      cerebral infarcts. Vascular risk factors associated with greater mortality were
      age (p < 0.001) and a history of cardiopathy (p < 0.05). CONCLUSIONS: Vascular
      risk factors which indicated worse prognosis were: age, type of ictus and a
      history of cardiopathy.

PMID- 9774823
TI  - [Evaluation of the Mullan's technique in the treatment of trigeminal neuralgia].
AB  - OBJECTIVE: The aim of the present study is to examine the operative technique and
      results of the treatment of trigeminal neuralgia (TN) by percutaneous
      microcompression of the trigeminal ganglion (Mullan's technique) in 20
      consecutive patients over 3 years. PATIENTS AND METHODS: The average age of the
      patients was 63 years. There were 8 men and 12 women. The operative technique is
      similar to Mullan and Lichtor's original description with some modifications.
      RESULTS: On average it takes 30 minutes to complete the procedure. On 2 occasions
      the catheter had to be replaced as the balloon burst without clinical
      repercussions. Detectable changes were noted in systemic blood pressure and
      cardiac rhythm in 10 cases. On 17 occasions the radiographic appearance of the
      balloon was pear-shaped and in the remaining cases it was oval or irregular.
      Follow-up ranged from 6 months to 3 years. All but 1 patient were initially
      relieved of pain and it was progressively possible to suspend treatment with
      carbamazepine. The recurrence rate was 25%. Mean time until recurrence was 18
      months. There was no relation between pain location and recurrence. Morbidity:
      some degree of transient cheek discomfort, herpes simplex perioralis, hypesthesia
      and masseter weakness were the rule. Meningitis in one case. CONCLUSIONS: Early
      results indicate that Mullan's technique provides a reliable, safe, cheap and
      effective, with low morbidity and no mortality.

PMID- 9774824
TI  - [Familial cerebral cavernomatosis associated with cutaneous angiomas].
AB  - OBJECTIVE, PATIENTS AND METHOD: We present a genealogical study of a person with
      familial cerebral cavernomatosis (CCF) discovered following study of a man who
      presented with status epilepticus at the age of 35 years. This had also affected
      another three members of the family consisting of a total of 43 persons, studied
      over six generations. RESULTS: In the family members studied we did not find
      cavernomas at other sites but there were dermatological lesions whose relation to
      cerebral cavernomas (CC) is discussed. CCs are the second commonest type of
      cerebral vascular malformations. Their major clinical features are epilepsy and
      cerebral haemorrhage. There are two forms of CC: a sporadic form with single
      lesions and a familial form with multiple lesions. Although the condition has
      been recognized since 1854, very little is known about it. Recently a gene
      causing the familial form has been found on chromasome 7. CONCLUSIONS: We discuss
      the clinical findings in this family with relation to descriptions in the
      literature. We emphasize the importance of MR in diagnosis of the condition and
      for detection of asumptomatic carriers. We consider a possible relationship
      between these findings and genes which have been mapped, and in view of recent
      genetic data, the hypothesis of a possible Spanish ancestor with the condition.

PMID- 9774825
TI  - [Carpal tunnel syndrome: clinical and neurophysiological correlation: review of
      100 cases].
AB  - INTRODUCTION: The diagnosis of carpal tunnel syndrome (CTS) continues to be
      neurophysiologically and clinically controversial. This study attempts to find
      the correlation between the subjective symptomatology and the neurophysiological
      affectation, establishing a diagnostic guide for the family doctor in order to
      recognize early CTS for referral to the specialist doctor. PATIENTS AND METHODS:
      After a sample of 100 cases with clinical suspicion of CTS, a clinical evaluation
      was made with the symptoms (paresthesias, pain, loss of strength), signs (Tinel,
      Phalen), and the neurophysiological evaluation with electroneurography (ENG) of
      the median and cubital nerve (sensory velocity (SV), motor distal latency (MDL)),
      and electromyography (EMG) of tenar eminence muscles. With this data an
      epidemiological study was made with correlation between the clinical and
      neurophysiological parameters. RESULTS: The patients with pain, loss of strength
      and Tinel's sign had significant alteration of the parameters of ENG and EMG.
      Tinel's sign had a sensitivity (SE) = 30.1% and a specificity (SP) = 73% for MDL,
      a SE = 32.5% and a SP = 88.2% for SV. Phalen's sign had a SE = 22.2% and a SP =
      94.6% for MDL, a SE = 18.1% and a SP = 94.1% for SV. CONCLUSIONS: The guide to
      recognize clinically the patients which must be studied neurophysiologically that
      have a high probability to suffer CTS is: diagnosis for motor alteration, pain
      (SE = 79%), loss of strength (SP = 86%) and Phalen's sign (SP = 94.6%). Sensory
      alteration: paresthesias (SE = 97%), Tinel's sign (SP = 88.2%) and Phalen's sign
      (SP = 94.1%).

PMID- 9774826
TI  - [Indicators of oxidative stress in aging rat brain. The effect of nerve growth
      factor].
AB  - INTRODUCTION AND OBJECTIVE: Increased oxidative stress during ageing and the
      neurodegenerative disorders associated with this has been described. The central
      nervous system is particularly vulnerable to oxidative damage because of its high
      energy requirements, high oxygen consumption, high tissue concentration of iron
      and relatively low levels of some antioxidant systems. Treatment with
      neurotrophic factors may reverse neurone deterioration and stimulate cholinergic
      activity in aged rats. It may have a similar neuroprotector effect against damage
      due to ischaemic reperfusion, hypoglycaemia, inflammation and other pathological
      conditions involving oxidative stress. In this study we determined some
      indicators of oxidative stress in rat brains during ageing and evaluated this in
      response to a plan of treatment with murine nerve growth factor (FCN) for 38
      days. MATERIAL AND METHODS: Biochemical techniques were used for determination of
      oxidative stress indicators. RESULTS AND CONCLUSIONS: We found that with age
      there was a significant increase in phospholipase A2 and superoxide dysmutase
      activity and concentration of hipoperoxidases, whilst the concentration of
      reduced glutathion fell. Catalase activity increased in the hippocampal and
      striate regions and decreased in the cortex and septal area. There was less
      oxidative stress in rats treated with FCN. In view of our results, we conclude
      that the level of oxidative stress increases with ageing, with significant
      differences between areas of the brain. The region most vulnerable to damage from
      species reactive to oxygen was the hippocampus, and the protective effect of FCN
      may be related to potentiation of antioxidant defenses.

PMID- 9774827
TI  - [The referral of hospitalized patients with cerebrovascular pathology. Where,
      when and why. A cross-sectional multicenter study of the referral of patients
      with ischemia and predisposing factors].
AB  - OBJECTIVES: Referral of patients with ictus on discharge from hospital is a daily
      problem for neurologists, both because of the suitability of one place or another
      for maximum recovery of the patient and because of the effect on average stay,
      complications and use of resources. The aim of this study was to determine where
      and when patients with ictus were referred and what factors affect whether a
      patient goes to one place or another. PATIENTS AND METHODS: A transversal
      multicentric study (3 months) using a questionnaire was sent to all Insalud
      hospitals in Aragon, recording data of 128 patients from four hospitals. There
      were questions on medical, functional, demographic and socio-economic factors
      which might affect referral. RESULTS: On discharge 20% of the patients did not
      return to their own homes. In 50% of the cases where patients went to a
      supporting hospital (SH) socio-economic factors were decisive and in 20% were the
      only cause. Referral to SH was related to functional state and type of ictus,
      need for nursing care or rehabilitation, age, sex, marital status and place of
      residence. CONCLUSIONS: Apart from clinical criteria, many socio-economic factors
      determine the need for referral of patients to one place or another.

PMID- 9774828
TI  - [Focal myositis: report of a case in pediatric age and review of the literature].
AB  - INTRODUCTION AND CLINICAL CASE: We present the case of a 13 years old boy with a
      year-old history of a painful tumour on the external and distal third of the
      right thigh. The imaging tests suggested a soft tissue tumour but the muscle
      biopsy revealed the typical findings of focal myositis. Focal myositis is a
      benign inflammatory pseudotumour of the skeletal muscle recognized as a distinct
      clinicopathological entity, but there have been descriptions of the cases
      initially diagnosed as focal myositis that have latter behaved as evident
      polymyositis. We have not found laboratory data to support a diagnosis of
      polymyositis in our patient. CONCLUSION: Although focal myositis is considered a
      self-limited disease, we believe a long-term clinical and biochemical follow-up
      is warranted, to confirm the absence of recurrence signs and/or the development
      of a generalized myopathy.

PMID- 9774829
TI  - [Hemimegalencephaly and pathological left handedness. A case report].
AB  - INTRODUCTION: Hemimegalencephaly is a disorder of neurone proliferation and
      migration, associated with excessive growth of all or part of one cerebral
      hemisphere, and variable degrees of pachygyria, polymicrogyria, neuronal
      heterotopy and gliosis of white matter. It is considered to be a rare
      malformation with severe encephalopathy, epilepsy resistant to treatment started
      early, contralateral hemiparesia and severe retardation of development. However,
      there may also be milder forms. The syndrome of pathological left handedness is
      associated with disorders of language, visuo-spatial changes and weakness and
      hypertrophy of the right limbs, with no family history of left handedness. It
      occurs in lesions predominantly of the left hemisphere which have occurred in the
      first six years of life. CLINICAL CASE: A 12 year old girl presented with a
      syndrome of pathological left-handedness and craniofacial asymmetry of the left
      hemisphere. MR showed the left ventricle and hemisphere to be of increased size
      and with focal hyperintensity in the white matter, and at the level of the left
      parietotemporoccipital region there was a thick cortex with little
      interdigitation of white and grey matter. CONCLUSIONS: Minor forms of
      hemimegalencephaly are probably more frequent than is generally believed. A high
      index of suspicion is necessary to identify them. They should be considered in
      cases of left handedness, craniofacial or bodily asymmetry, cutaneous hamartomas,
      persistent electroencephalographic asymmetry and asymmetry on neuroimaging with
      an enlarged ventricle and homolateral hemisphere. Study of this may give
      information which is useful for understanding plasticity and mechanisms of
      recovery and functional compensation of immature nerve tissue.

PMID- 9774830
TI  - [Bilateral medial bulbar infarct related to dolichoectasia of the vertebral
      artery].
AB  - INTRODUCTION AND CLINICAL CASE: A 58-year-old hypertensive man presented with the
      sudden onset of quadriplegia and inability to protrude the tongue. Magnetic
      resonance imaging showed a bilateral medial medullary infarction associated with
      an abnormally dilated and partially occluded vertebral artery. CONCLUSION: This
      is the first clinicoradiological report of a bilateral medial medullary
      infarction related to vertebral artery dolichoectasia.

PMID- 9774831
TI  - [From writer's cramp to butcher's spasms: a case of interprofessional dystonia].
AB  - INTRODUCTION: Occupational or professional dystonia is a focal motor dystonic
      disorder which affect motor programs necessaries for the exercise of the
      patient's profession. Clinical case. A patient with writer's cramp in the
      childhood presented at the age of 22 years a new dystonia, which we name
      'butcher's spasm', giving rise to a laboral incapacity. Neurological exam was
      normal except for right arm distal (writer's cramp) and proximal dystonias
      (butcher's cramp), with intentional tremor in the upper extremities. We
      classified, after complementary exams, the disease as idiopathic. CONCLUSIONS:
      Idiopathic focal dystonias can progress to segmentary or multifocal dystonias,
      and, in exceptional cases as ours, can interfere with two different professional
      activities.

PMID- 9774832
TI  - [Lafora disease and the two first cases of Alzheimer's disease published in
      Spain].
AB  - Gonzalo Rodriguez Lafora (Madrid 1886-1971) finished his neuropathological
      training in the Nervenklinik in Munich, together with Alzheimer. In 1910 he took
      over from Achucarro in the mental hospital in Washington. In 1911, the year he
      described amylaceous bodies in myoclonic epilepsy, he had the chance to study a
      demented person, a former soldier in the American Civil War, who had progressive
      deterioration of his mental functions. Both clinical and anatomopathological
      studies were very detailed. He shared the discovery of granulovacuolar
      degeneration with Simchowitz. It was the eighth case in the literature. The
      second case (and third American patient) in 1914 was a demented person with
      goitre, also in Washington mental hospital, who was studied by means of a full
      series of psychological tests, and the autopsy findings were later described.
      These studies were not published in English, and perhaps for this reason were not
      as widely known as they should have been.

PMID- 9774833
TI  - [Atrial fibrillation of non-valvular origin and anti-coagulation: a promising
      opportunity for the prevention of cerebral infarct... if there is participation
      of those working in primary care].

PMID- 9774834
TI  - [Hyperbaric oxygen in vertebro-basilar ischemia].

PMID- 9774835
TI  - [Neurophysiologic study of Alpers syndrome].

PMID- 9774836
TI  - [Carbamazepine-related SIADH].

PMID- 9774837
TI  - [A diagnostic strategy in persistent hyperparathyroidism].
AB  - BACKGROUND: Primary operations for hyperparathyroidism performed by experienced
      surgeons has a success rate of about 95% without any preoperative localization.
      After unsuccessful cervicotomy, localization studies must be performed in order
      to define the surgical approach. The objective of our retrospective studies was
      to determine the accuracy of non invasive and invasive localization studies in
      patients with persistent hyperparathyroidism. METHODS: The present reoperative
      series involved 7 patients with persistent hyperparathyroidism. Six patients came
      from a series of 140 operated on at the department of Prof. J. Marescaux from
      1991 to 1993 (success rate of 95.7% in cervical exploration). Patient n. 7 came
      from another department. RESULTS: After negative initial cervicotomy, non
      invasive localization procedure are undertaken, but with a high incidence of
      false-positive results (9% to 75%). Among available invasive techniques, it has
      been chosen to sample blood from large veins in the neck and mediastinum for
      Parathyroid Hormone (1-84 PTH) determination and to realise angiography for
      locating parathyroid adenomas as well as for vein mapping. Their combination
      permitted to localize all lesions. CONCLUSIONS: The specificity of serum
      concentration of 1-84 PTH determination by catheterization of cervical and
      mediastinal veins (100%) combined to the sensitivity of angiography (82%) allowed
      to obtain good result in parathyroid localization in persistent
      hyperparathyroidism.

PMID- 9774838
TI  - [Papillary carcinoma of the thyroid. A uni- and multivariate analysis of the
      factors affecting the prognosis inclusive of surgical treatment].
AB  - METHODS: A total of 463, out of 677 patients operated on for papillary thyroid
      carcinoma between 1967-1995, were selected, on the basis of a 5-year minimal
      follow-up (max 28, mean 11.15 +/- 5.29), for uni and multivariate analysis of
      survival curves. Patient sex, age over and under 45 years, tumour size smaller
      and larger than 15 mm, stage, any TNM parameter, histological variety, surgical
      procedure on the thyroid and nodes were the factors assessed in order to express
      the prognosis. RESULTS: Male:female ratio was 1:3, the mean age 42.2 years; only
      25.9% of patients presented with smaller than 15 mm tumor, about 57% with
      positive nodes and 8.85% with distant metastases; total or near total
      thyroidectomy was performed in 86% and nodal dissection in 70% of patients. The
      5, 10, 15, 20 year survival rate resulted to be 96.94%, 94.36%, 91.38% and
      88.69%; 23 patients, but none aged less than 45 years, died (poorly
      differentiated and locally advanced carcinoma). Age over 45 years, T4 and M+
      stages resulted of high prognostic importance while nodal involvement,
      interrelated with T and M, showed no independent impact; stage gradually worsened
      but no difference was found between stage I and II. Adverse effect of male sex
      resulted from its interrelation with more advanced stages. The relapse rate was
      found higher in male sex and in patients aged over 45 years, interrelated with T
      and N extension: no tumor smaller than 15 mm recurred and no relation was found
      between recurrence and surgical procedure. CONCLUSIONS: Longer follow-up is
      needed to compare the higher curative effectiveness of total thyroidectomy and
      nodal dissection versus more conservative treatments.

PMID- 9774839
TI  - [Surgical endoscopy of the airways].
AB  - METHODS: Between April 1993 and April 1996, 146 endoscopic procedures were
      performed in 128 patients (144 with Nd:YAG laser) with benign or malignant
      obstructions of the airway. Removal of foreign bodies are not included in this
      series. Twenty resections were performed with the flexible fiberoptic
      bronchoscope under local anesthesia and 126 with the rigid tube under general
      anesthesia. Power settings were always between 20 and 35 Watts. Eighteen
      procedures were performed in emergency. Fifteen patients had a benign
      postintubation tracheal stricture (20 treatments-11 Dumon stents and 1 Montgomery
      tube). Eighty-two patients (90 treatments-12 stents) had malignant lesions of the
      airways (trachea 11, carina 2, RMB 22, LMB 27, TI 11, LULB 3, RULB 2, LILB 4).
      Laryngeal, tracheal or bronchial granulations were present in 19 patients (21
      treatments). Other lesions were present in 11 patients (14 treatments-6 stents).
      RESULTS: Major complications occurring during laser resections were bleeding (2),
      hypoxia (1) and cardiac arrhythmia (2); 2 patients died 24 hours after the
      procedure for cardio-respiratory failure. The airway calibre was improved in 100%
      of patients with benign lesions and 82.4% of patients with malignancy. In the
      latter group the trachea, main stem bronchi and truncus intermedius calibre was
      improved better than the lobar bronchi. All patients with malignancy underwent
      chemo-radiotherapy without respiratory distress. CONCLUSIONS: Nd:YAG laser
      therapy is a safe and effective mean of releasing airway obstructions; indwelling
      stents contribute to further improve the results.

PMID- 9774840
TI  - [Lung resections for cancer in the elderly].
AB  - BACKGROUND: The purpose of this study is to investigate the value of surgical
      treatment for lung cancer in the elderly. Results are compared with findings in
      younger patients operated on during the same period (1985-1990). METHODS: 137
      patients 70 years of age or older (range: 70 yrs-87 yrs) (group A) underwent
      surgical resection [pneumonectomy in 19 (13.8%), lobectomy or bilobectomy in 84
      (61.3%), segmentectomy or wedge resection in 22 (16%)]. In group B (younger
      patients) 561 were treated by pneumonectomy in 156 (27.8%), lobectomy or
      bilobectomy in 294 (52.4%) and segmentectomy or wedge resection in 64 (11.4%).
      RESULTS: The overall 2-year survival rate was 64.6% in group A and 61.4% in B.
      The 5-year survival rate was 36.2% (group A) and 43.2% (group B). CONCLUSIONS:
      These data suggest that advanced age should not be a contraindication to curative
      pulmonary resections. More attention must be paid to pre-codiseases of the
      increasing risk of postoperative complications.

PMID- 9774841
TI  - Prognostic factors in gastric cancer evaluated by using Cox regression model.
AB  - OBJECTIVE: To identify the most relevant short-term predictor variables in
      gastric cancer removal. EXPERIMENTAL DESIGN: A retrospective survival analysis
      executed by using the Cox regression model; the follow-up period is included
      between 18 and 90 months. SETTING: A district general hospital surgery unit:
      "Divisione di Chirurgia Generale, Ospedale Civile di Urbino" (Marche, Italy).
      SUBJECTS: One hundred and twenty nine consecutive patients operated for gastric
      cancer. INTERVENTIONS: Surgery (total or subtotal gastrectomy). MAIN OUTCOME
      MEASURE: Survival times. RESULTS: Lymph node involvement (N) (p < 0.0001), cancer
      intraparietal extension (T) (p < 0.001) and the age of the patients (p < 0.05)
      have been recognized as significant prognostic factors. CONCLUSIONS: Results show
      that the short-term prognosis largely depends on both the earliness of the
      diagnosis and the age of the patients.

PMID- 9774842
TI  - [Echo-guided fine-needle biopsy for the diagnosis of hepatic angioma. A report on
      114 cases].
AB  - METHODS: Personal experience with fine-needle aspiration biopsy (FNAB) performed
      in 114 patients (42 males and 72 females) with hepatic angiomas, in whom imaging
      techniques did not allow a definite diagnosis, is reported. FNAB was made on
      57.9% of the cases for atypical US pattern of the nodule, on 52.6% for a previous
      cancer history, with both conditions on 10.5%. The procedure was carried out by
      cyto-assistance for collecting material and a rapid stain diagnosis with an
      average of 2 biopsies per patient. Diagnostic accuracy was evaluated with
      following laparoscopy in 25 cases; surgery in 4 cases; angiography in 6 cases and
      US follow-up for 1 year at least in 78 cases (1 drop-out). RESULTS: One false
      negative and 4 false-positives were detected with an overall accuracy of 96%. Two
      minor accidents were observed, due to a profuse bleeding of giant angiomas and
      resolved with medical care. CONCLUSIONS: Therefore, in case of angiomas larger
      than 5 cm, the use of laparoscopy after FNAB to control the bleeding and to
      confirm the diagnosis is suggested.

PMID- 9774843
TI  - Immunohistochemical assessment of peroxidase-like immunoreactivity in the thyroid
      gland and its correlation with biochemical assay.
AB  - BACKGROUND: Peroxidase content has been recently evaluated in normal thyroid and
      in different thyroid disorders by biochemical, histochemical, ultrastructural and
      immunocytochemical methods. Nevertheless immunocytochemical detection of thyroid
      peroxidase in thyroid samples conventionally processed for histology has never
      been done using a commercially available antibody, neither its correlation with
      the biochemical activity on adjacent samples. METHODS: In this study we have
      analyzed normal thyroid tissue (3 patients), follicular adenoma (2 patients) and
      multinodular goiter (2 patients) conventionally processed for histology and
      stained by immunocytochemistry (Avidin Biotin System) using a polyclonal (rabbit)
      antibody for horseradish peroxidase (Serotec). Biochemical assay was performed on
      adjacent samples according to Hosoya method. RESULTS: Normal thyroid showed
      peroxidase immunoreactivity in the majority of follicular cells; neoplastic cells
      of adenomas were variably stained. Biochemical assay showed positive correlation
      with ICC ranging from 20.4 micrograms/mg/prot a in multinodular goiter to 42.12
      in normal thyroid, up to 122 of follicular adenoma. CONCLUSIONS: Peroxidase
      content in the thyroid gland may be of clinical interest in several thyroid
      diseases, and in this study we have demonstrated that thyroid peroxidase can be
      detected by ICC in routinely processed thyroid samples using a commercially
      available antibody.

PMID- 9774844
TI  - [The role of imaging diagnosis in the study of intestinal infarct].
AB  - Acute mesenteric insufficiency is a surgical emergency with a difficult
      methodological approach. Its high mortality is mainly due to delay in the correct
      diagnosis. In turn, this is due to the lack of specificity, specially in the
      early-middle phase, of the clinical presentation, laboratory data, and plain
      abdominal radiographic findings. In front of this uncertainty, some authors
      advocated an "aggressive" approach with early use of angiography (nevertheless at
      risk of a high rate of negative examinations), other remained on more wait-and
      see or fatalist positions, and other evaluated the possible diagnostic impact of
      noninvasive methods alternative to angiography. With the purpose of a correct
      employment from the surgeon of the various diagnostic tools actually available,
      we illustrated in this review the possibilities and limitations of the methods
      proposed in the evaluation of bowel infarction: plain abdominal radiography,
      gastrointestinal tract contrast studies, angiography, sonography, computed
      tomography (CT), magnetic resonance imaging (MRI).

PMID- 9774845
TI  - [A complicated paraesophageal diaphragmatic hernia. A clinical case report].
AB  - A case of diaphragmatic paraesophageal hernia complicated by omentum and gastric
      incarceration is reported. The pure paraesophageal hiatal hernia is a rare
      entity. The symptoms and complications are caused by the anatomic defect and not
      by gastroesophageal incompetence. Chronic, recurrent, asymptomatic blood-loss
      anemia is the most common complication. Gastric volvulus is frequent in which the
      stomach herniated in a huge parietal peritoneal sac in the chest behind the
      heart. Volvulus may be a chronic recurrent problem or an acute life threatening
      complication. The diagnosis depends on the patient's symptoms and the
      demonstration by radiography, but difficulties may occur in the presence of
      complications, as in the case reported. Surgical repair is indicated, with sac
      excision and hiatusplasty.

PMID- 9774846
TI  - [A gastrocutaneous fistula secondary to the percutaneous drainage of a pancreatic
      abscess. A case report].
AB  - Pancreatic abscesses are a frequent complication of acute pancreatitis and their
      percutaneous drainage is usually accepted. A 76 years-old male patient admitted
      for acute pancreatitis (Ranson 3 at admission) has been treated with conservative
      therapy and percutaneous US directed drainage of the abscess, located between the
      tail of the pancreas and the gastric fundus. This kind of drainage was able to
      empty the abscess satisfactorily but it caused the onset of a gastrocutaneous
      fistula. This one was sutured on the gastric side by metal clips placed by
      gastroscopy. The patient was discharged on the 60th day in a good condition. An X
      ray investigation with gastrografine before the drainage removal is therefore
      recommended.

PMID- 9774847
TI  - [A rare case of a perforated diverticulum of the cecum].
AB  - A rare case of peritonitis by cecal perforated diverticulum which was diagnosed
      after surgery by histology is reported. Preoperative diagnosis is often ignored
      and, in rare cases, is not always clear at laparotomy. Clinical aspects,
      diagnostic procedures, histological picture and surgical treatment are described.
      In the literature diverticula are classified as "solitary" and "multiple",
      "congenital" and "acquired", "true" and "false" and finally "usual type" and
      "hidden variant". The treatment of cecal acute diverticulitis is, in the majority
      of patients, surgery. Simple resection of the diverticulum and suture of the
      breach in double layer is the elective operation of non-complicated diverticulum
      or with an inflamed projection from the cecal wall ("usual type"). Segmental
      resection of colon or "right hemicolectomy" is recommended when a precise
      diagnosis is not possible and in complicated diverticula ("hidden variant"). On
      the basis of personal experience it is underlined that diagnosis is rarely made
      preoperatively since the clinical picture suggests an acute appendicitis. If
      there are some doubts for appendicitis, a incidental tumor or possible perforated
      diverticulum of the cecum should be considered and urgent surgery is mandatory.

PMID- 9774848
TI  - [Infected aneurysms of the abdominal aorta. Personal case reports].
AB  - Two cases of infected aneurysms of the subrenal abdominal aorta observed in the
      last year are reported. In this study some specific aspects of this unusual
      pathology are analyzed: the high mortality rate, the difficulties involved in the
      diagnosis and the surgical solutions.

PMID- 9774849
TI  - [Retroperitoneal tumors. Observations on 8 cases].
AB  - The incidence of retroperitoneal tumours is extremely low (0.01-0.2% of all
      neoplasias). Their onset is atypical and a palpable mass is often clinically
      evident, together with abdominal pain and fever. A major impetus has been given
      to diagnosis by instrumental techniques, and in particular CT. Surgical treatment
      is required for these tumours. The prognosis does not improve following radio and
      chemotherapy. The authors describe 8 cases referred to their attention between
      1980 and 1995.

PMID- 9774850
TI  - [A primary pleomorphic adenoma of the parapharyngeal space].
AB  - The rarity of benign primary neoformations in the parapharyngeal space associated
      with aspecific clinical symptomatology often leads to the identification of large
      size lesions with deformation of the lateral wall of the pharynx and homolateral
      hemiplate. The improved diagnostic specificity of radiological instruments like
      CT and NMR allows a precise topographical localisation of the mass and the
      diagnosis of its nature in 90% of cases. The deep position of the neoplasia makes
      it necessary to search for the most conservative surgical approach possible that
      enables a sufficiently broad operating field to be obtained for complete exeresis
      and the control of neck vessels. This paper describes the therapeutic protocol
      used and makes a critical revision of the surgical approaches in an exemplary
      case of primary pleomorphic adenoma in this region.

PMID- 9774851
TI  - [Plasma-cell granuloma of the mediastinum].
AB  - Plasma-cell granuloma of the mediastinum is an unusual non-neoplastic lesion; a
      case of rare mediastinal localization is reported. Only the histopathological
      examination leads to a correct diagnosis. Since the possibility of local
      recurrence has been described, total excision is requested. Video-assisted
      thoracic surgery technique may be difficult to use in the management of these
      mediastinal tumors due to adhesions between the mass and the surrounding tissues.
      Complete open resection is the treatment of choice.

PMID- 9774852
TI  - Tardive presentation of congenital cystic adenomatoid malformation of the lung.
AB  - Congenital cystic adenomatoid malformation (CCAM) of the lung is a neonatal
      disease not often found after the first year of life and extremely rare in
      adults. Three cases of CCAM, one in a ten-year-old girl and two in adults, are
      reported. An understanding of this disease is important because, although
      relatively rare, it is one of the most frequent causes of neonatal respiratory
      distress. Greater awareness of the condition and its early detection would also
      reduce the number of cases found at a later age.

PMID- 9774853
TI  - [Video laparoscopic adrenalectomy. The authors' personal experience].
AB  - Personal experience on two cases of laparoscopic adrenalectomy, operated, one on
      the right and the other on the left side, during 1996 is reported. The surgical
      technique, using a lateral decubitus and a transperitoneal approach is described,
      as well as the postoperative outcome. The laparoscopic approach to adrenal
      surgery seems to be "ideal", since it has a low "trauma ratio" (surgical
      procedure/access) with an anatomical an virtually bloodless dissection.

PMID- 9774854
TI  - [The treatment of phimosis in childhood without circumcision: plastic repair of
      the prepuce].
AB  - BACKGROUND: To device a new surgical technique of preputial plasty for the
      treatment of phimosis, as an alternative to circumcision, easy to perform, which
      preserves the normal function of the prepuce. METHODS: The new technique consists
      of three lengthwise incisions of the stenosing wase and their diagonal suture,
      the triple incision preputial plasty, described by others, modified adding
      frenulotomy and two more incisions between the previous ones, which are left to
      heal spontaneously. This technique has been applied on 22 children over a period
      of 24 months, with a follow-up of six-twenty-four months. RESULTS: The technique
      is easy to perform. All check-ups show good cosmetic results, no recurrence,
      normal preputial anatomy and function. It is important to continue "preputial
      gymnastics" until stabilization. CONCLUSIONS: The devised technique fully
      succeeds in preserving a normal prepuce, it is easier to perform and safer than
      other preputial plasties and it may be carried out in all cases of phimosis in
      pediatrics. The good results achieved encourage us to continue along this path,
      hoping that the technique will be largely applied.

PMID- 9774855
TI  - [The coronal approach in maxillofacial surgery. Notes on the surgical anatomy].
AB  - INTRODUCTION: In the light of personal experience and of the modern advances in
      surgical anatomy, the surgical approach and practice in coronal access is
      described. For a long time this approach has been considered unusual owing to the
      risk of damaging the frontal branch of the facial nerve. ANATOMY: The SMAS
      includes the galea capitis which in temporal region is named superficial temporal
      fascia; under the galea there are the subaponeurotic avascular plane by Merkel
      and the periosteum. In the temporal space the periosteum (named temporal fascia)
      is composed of the superficial fold and deep fold. The frontal branch of the
      facial nerve lies under the superficial temporal fascia, and where it crosses the
      zygomatic arch is separated only by the superficial fold of the temporal fascia
      and by areolar tissue. SURGICAL APPROACH: The incision is made deeply to the
      subaponeurotic areolar tissue following, about 4 cm posterior to the hairline.
      The periosteum is incised at 2 cm above the superior orbital margin. Four cm
      above the bony lateral canthus and at 7 cm on the tangential to the zygomatic
      arch, the incision is made deeply to the superficial fold of the temporal fascia
      and the interfascial vascular fat. CONCLUSIONS: If the approach is correct, the
      coronal access is considered an easy and very safe way. In personal experience
      important complications have not been observed, while the esthetic results have
      been remarkable and with no visible scars.

PMID- 9774856
TI  - [Cranioplasty with polymethylmethacrylate. The clinico-statistical
      considerations].
AB  - BACKGROUND: The main purpose of the reconstruction of the cranium is the
      protection of the brain. Besides we have to consider important functional and
      aesthetic necessities in order to achieve satisfactory results. METHODS: Thirty
      six clinical cases, operated from November 1991 to June 1996, in which the
      reconstruction of the cranial vault is carried out by a polymethylmethacrylate
      acrylic resin are analysed. The causes and locations of the most common bone
      defects and the main indications for reconstruction are examined. While the
      repair of the osseous gaps caused by neoplasms is immediate, in the traumatic
      occurrences, in order to reduce the probability of infectious complications, an
      average time of 11 months elapsed from the first operation. The surgical
      technique, with slightest alterations, is the same in all the presented cases,
      preparing the acrylic resin straight on the operating table. The resin, moulded
      and adapted to the defect until its complete hardening, presents, thanks to its
      properties, manifold advantages (and few real disadvantages). RESULTS: The
      results, in terms of complications, are very satisfactory, with an infectious
      rate of 2.7%. Besides, in one third of the patients, a considerable clinical
      improvement after the repair has been observed. CONCLUSIONS: According to
      personal experience, it is possible to affirm that polymethylmethacrylate, with
      its remarkable plasticity and stability in time, can always guarantee a
      satisfactory functional and aesthetic result.

PMID- 9774857
TI  - [The use of prosthetic meshes in the surgical treatment of inguinal hernia: the
      costs and profits for the local health screening unit].
AB  - BACKGROUND: Inguinal hernioplasty represents one of the most frequently performed
      surgical operation. The recent introduction of prosthetic mesh made Bassini
      operation obsolete, with more space gained by the newly developed "tension-free"
      and "sutureless" surgical techniques. This new approach, however, results in
      increased initial costs for the hospital, due to the purchase of mesh materials.
      On the other hand a reduction of overall expenses for a single hernia repair
      should be expected. In this work an attempt is made to verify this, by
      calculating the cost-benefit ratio of different techniques for hernia repair.
      METHODS: The type and amount of materials used in a standard Bassini hernia
      repair, Lichtenstein and Trabucco have been examined. The amount of anesthetic
      drugs required, the average hospital stay and time away from work were recorded
      too. The costs of the three operations considered, not including routine expenses
      (operating room, bed sheet, etc.) have been estimated. RESULTS: Lichtenstein and
      Trabucco repair performed in local anesthesia (L. 1.354.120, L. 1.567.120) were
      cheaper than Bassini (L. 2.820.950). CONCLUSIONS: Since the system of diagnosis
      related group offers a fixed amount of reimbursement for hernia repair (L.
      3.247.000), the extensive use of tension free and sutureless methods, offers
      better profit for the Hospital. Last but not least, tension free hernia repair
      ensures short hospital stay, less postoperative pain, good compliance and better
      quality of life for the patient.

PMID- 9774858
TI  - [Endocrine tumors of the pancreas. Review of 30 years of research].

PMID- 9774859
TI  - Wolf-Hirschhorn syndrome: case report and review of the chromosomal aberrations
      associated with diaphragmatic defects.
AB  - A female fetus showing severe growth retardation was delivered at 31 weeks of
      gestation because of fetal distress. At birth, the infant showed bradycardia and
      no spontaneous breathing. Although high frequency oscillatory ventilation was
      started, severe asphyxia persisted and the infant died of respiratory
      insufficiency. At the autopsy, the propositus showed microcephaly, prominent
      glabella, broad bridge of the nose, ocular hypertelorism, poorly differentiated
      and low-set ears, bilateral palatoschisis, and micrognathia. Midline closure
      defects of the cervical spine bodies, lower jaw, and skull base were seen at
      postmortem radiography. An extreme hypoplasia of both lungs, a large defect of
      the left diaphragm with upward displacement of viscera, and multiple cortical
      cysts in both kidneys were seen at postmortem examination. Karyotyping revealed a
      chromosomal imbalance with 46, XX, del(4) (pter-->13), characterizing the Wolf
      Hirschhorn syndrome. Because diaphragmatic defects can occur in association with
      specific recognizable patterns of human malformation careful pathologic and
      genetic workup of all affected infants in crucial for accurate genetic
      counseling.

PMID- 9774860
TI  - [Sudden infant death syndrome (SIDS): a case with accessory pathways and
      resorptive degeneration].
AB  - We report the case of a 71 day-old female infant victim of SIDS. Histological
      observations were focused on the cardiac conduction system. We observed accessory
      pathways of Mahaim type with areas of resorptive degeneration. These findings,
      associated with particular conditions and/or neurovegetative stimuli, could cause
      potentially malignant arrhythmias.

PMID- 9774861
TI  - [Visceral pleura lipoma: a previously undescribed localization and review of the
      literature on pleural lipomas].
AB  - Pleural lipomas are rare, often asymptomatic tumours arising from the parietal
      pleura. Whereas radiographic signs of pleural lipomas are aspecific, computed
      tomography and magnetic resonance imaging permit accurate preoperative diagnosis.
      We describe the clinical-pathologic features of the first case of lipoma arising
      from the visceral pleura, accidentally discovered in a woman during removal of
      chest schwannoma. A review of literature concerning pleural lipomas is also
      presented.

PMID- 9774862
TI  - [Peritoneal cystic mesothelioma].
AB  - Cystic mesothelioma of peritoneum is a rare neoplasia that was identified as a
      individual entity by ultrastructural and immunoistochemical studies. It is more
      frequent in young woman and often it tends to recur. Because of its rarity and
      difficulty in differential diagnosis, the Authors describe a case of cystic
      mesothelioma observed.

PMID- 9774863
TI  - ["Black adenoma" associated with medullary nodular hyperplasia in the ipsilateral
      adrenal gland. Case report and review of the literature regarding "mixed" cortico
      medullary pathology].
AB  - BACKGROUND: Pigmented or "black" cortical adenoma is a rare variant of the
      compact or eosinophilic cell type of adrenal gland cortical adenoma. Usually it
      is non functioning so representing an incidental finding at autopsy, but rare
      cases producing Cushing's syndrome or hyperaldosteronism have been reported. The
      simultaneous occurrence of a cortical adenoma and pheochromocytoma in the
      ipsilateral adrenal gland is an extremely rare event, which has been so far
      described only seven times with the cortical adenoma always being of the usual
      yellow or clear cell type. So far no case of "black adenoma" associated with a
      proliferative condition of the ipsilateral adrenal medulla has ben described.
      CASE REPORT: A case of functioning pigmented ("black") cortical adenoma in a male
      patient affected by Cushing's syndrome associated with asymptomatic medullary
      nodular hyperplasia in the ipsilateral adrenal gland is described. The results of
      light microscopy, histochemistry, immunohistochemistry, and electron microscopy
      studies are presented. It is worthy of note the finding of two types of pigment
      granules (lipofuscin type, neuromelanin type) observed at elecatron microscopy.
      CONCLUSIONS: The authors underline the difficulty of classifying adrenal
      medullary nodules and the arbitrarity usually adopted in separating nodular
      adrenal medullary hyperplasia from early neoplasia (pheochromocytoma). Thus
      nodular medullary hyperplasia in this case could also be interpreted as an early
      neoplastic condition. The case herein presented is the first report of a combined
      cortico-medullary proliferative process in which a "black" adenoma is involved.

PMID- 9774864
TI  - [MALT gastric lymphoma: update].

PMID- 9774865
TI  - [Needle aspiration cytology of the pancreas].

PMID- 9774866
TI  - Electronic publishing--a challenge in medical information exchange.

PMID- 9774867
TI  - [Significance of the phrase "anatomo-clinical" and its use in the writings of
      Armando Businco].

PMID- 9774868
TI  - [Forced expiratory test, maximum ventilation, resistance and flow-volume curve-
      possibilities of a comprehensive characterization of airway obstruction and
      respiratory reserve].

PMID- 9774869
TI  - [Effect of GLP-1 and amylin on lung circulation, the bronchial system and
      systemic circulation in isolated ex vivo organ cultures of the rat].

PMID- 9774870
TI  - [Quantification of inhaled exposure to alpha-amylase in 2 bakeries].
AB  - BACKGROUND: Baker's asthma and baker's rhinitis are among the most frequent
      occupational diseases. A major cause is the high exposure to flour dust in the
      workplace and to allergenic enzymes like alpha-amylase from Aspergillus oryzae
      (allergen name: Asp o 2). METHODS: To quantify allergen exposure in the
      workplace, 31 personal dust samples in a conventional small bakery (six workers)
      and in a biobakery (seven workers) were collected. Using a recently developed two
      site enzyme-linked immunosorbent assay based on monoclonal antibodies to alpha
      amylase from Aspergillus oryzae, the allergen content of these dust samples was
      determined. RESULTS: Dust exposure in the biobakery was in the range between 3.5
      and 12 mg/m3 (median: 5.2 mg/m3) and in the conventional bakery between 0.9 and
      118 mg/m3 (median 8.5 mg/m3). 23 out of 31 exposure measurements showed values
      higher than 4 mg/m3 (threshold limit value for inhalable dust). In the biobakery,
      no fungal alpha-amylase could be detected. 15 out of 17 samples taken in the
      conventional bakery contained fungal alpha-amylase in the range between 0.2 and
      88 ng per mg dust. The geometric mean of alpha-amylase exposure in this bakery
      was 13 ng Asp o 2/m3, and the maximum exposure was 4.8 micrograms/m3. In four
      cases, fungal alpha-amylase was detected although exposure to dust was below the
      threshold limit of 4 mg/m3. CONCLUSIONS: This study in two German bakeries shows
      that preventive measures to reduce contact to allergens have not been
      sufficiently realised. Relevant alpha-amylase exposure occurred at low dust
      levels illustrating that dust measurements are not adequate to control alpha
      amylase exposure. For fungal alpha-amylase an additional threshold limit should
      be established.

PMID- 9774871
TI  - [Recommendations of the German Society of Pneumology for inhalational provocation
      testing in exogenous allergic alveolitis. Exogenous-Allergic Alveolitis Study
      Group of the German Society of Allergology and clinical Immunology and the German
      Society of Pneumology].

PMID- 9774872
TI  - [Recommendations for therapy of community-acquired pneumonia. German Society of
      Pneumology].

PMID- 9774873
TI  - [Recommendations for structure and contents of train-the-trainer seminars for
      educating patients with chronic obstructive respiratory tract diseases].

PMID- 9774874
TI  - [Ambulatory community pneumologic prevention and rehabilitation of chronic
      obstructive respiratory tract diseases--status, prospects and need for research].

PMID- 9774875
TI  - [Criteria for the etiologic assessment of pneumonia in the patient with
      mechanical ventilation].

PMID- 9774876
TI  - [Malaria, Africa, and traveling: a risk triangle].

PMID- 9774877
TI  - [Trend in mortality due to diabetes mellitus. Andalusia, 1975-1994].
AB  - BACKGROUND: Relevant differences regarding the temporal evolution of mortality
      attributed to diabetes mellitus in developed countries have been observed. This
      work focuses on mortality due to diabetes mellitus in Andalusia during the 1975
      1994 period and causes that can explain this evolution are analyzed. METHODS:
      Deaths caused by diabetes mellitus occurred during the period 1975-1994 were
      obtained. For each gender the following parameters were calculated: crude
      mortality rates, age-adjusted rates by means of the direct method using the
      European population as standard, adjusted rates by age of the potential years of
      life lost and specific rates by 5-year period groups, for the twenty years
      studied. Standardized rates were adjusted to a regression straight line regarding
      the death year and theoretical rates were calculated. With these calculations the
      percentages in changes of mortality rates were estimated and a projection has
      been calculated until the year 2000. RESULTS: From 1975 to 1994 the crude
      mortality rates due to diabetes mellitus had increased slightly both in men and
      women. The adjusted rates by age have decreased by 19.35% in men and 28.38% in
      women. The remaining elaborated indicators have decreased more markedly; to note
      PYLL, with a decrease from 115.2 to 51.25 in men and from 132.98 to 31.94 in
      women for 100,000 persons/year. CONCLUSIONS: The mortality rates due to diabetes
      mellitus in Andalusia have decreased both in men and in women, mainly because of
      the marked decrease in premature mortality, which may indicate an improvement in
      health care to the diabetic patient.

PMID- 9774878
TI  - [Evaluation on non invasive diagnostic tests for the second look in epithelial
      ovarian cancer].
AB  - OBJECTIVE: To determine the usefulness of diagnostic tests performed before a
      second look laparotomy in patients with epithelial ovarian cancer. STUDY DESIGN:
      Thirty-three patients with epithelial ovarian cancer attended at Fundacion
      Jimenez Diaz from 1984 to 1995 were studied. All patients initially underwent
      cyto-reducing surgery, followed by at least six platinum-based chemotherapy
      cycles. Prior to second look laparotomy all patients were evaluated by
      computerized tomography (CT) of the pelvis and abdomen, CA-125, pelvic-abdominal
      echography and gynecologic examination. To evaluate sensitivity, specificity,
      positive predictive value and negative predictive value for each test contingency
      tables were used. RESULTS: Eleven out of the 33 second look patients (33%) had
      histologic or cytologic evidence of disease. Six out of the eleven positive
      second look had a positive CT prior to second look (sensitivity of 55%). CT
      showed lack of disease in 21 out of the 22 negative second look cases
      (specificity 95%). Positive and negative predictive values of the test were 86%
      and 81%, respectively. Nine cases out of the 28 who had a CA-125 obtained had a
      positive second look. Four out of these nine patients had an increased CA-125
      value (sensitivity 44%, specificity 95%, positive predictive value 80% and
      negative predictive value 78%). Sensitivity, specificity, positive predictive
      value and negative predictive value of physical examination and echography were
      36%, 100%, 100%, 76% and 27%, 95%, 75%, 72%, respectively. On the other hand,
      sensitivity, specificity, positive predictive value and negative predictive value
      of all tests taken together were 64%, 91%, 78% and 83%, with a rate of false
      negative results of 17% and a rate of false-positive results of 22%. CONCLUSION:
      Pelvic-abdominal computerized tomography, CA-125, pelvic-abdominal echography and
      gynecologic examination can be an alternative to second look laparotomy for the
      diagnosis of persistence or recurrence of the disease in patients with epithelial
      ovarian cancer.

PMID- 9774879
TI  - [Percutaneous gastrostomy under fluoroscopic guidance. A one year experience].
AB  - The nasogastric tube has traditionally been used as nutritional support for
      patients with head and neck cancers. We propose the percutaneous gastrostomy
      under fluoroscopic guidance as a part of therapy in selected patients with head
      and neck cancers, or in those who have chronic aspiration and dysphagia secondary
      to neurologic impairment. Our one-year experience with our series of nasogastric
      tube is reviewed.

PMID- 9774880
TI  - [Severe and complicated malaria. Report of six cases].
AB  - Six patients with severe and complicated falciparum malaria (6.7 +/- 2.7 WHO
      criteria) were admitted to our Intensive Care Unit. All patients acquired the
      disease while travelling in tropical Africa without appropriate chemoprophylaxis.
      The clinical manifestations included hyperpyrexia (all patients), chills (4),
      sweating (2), asthenia (3), anorexia (2), headache (1), arthralgias (1), vomiting
      (4), diarrhoea or abdominal discomfort (3), jaundice (2) and disturbances of
      consciousness (4). All patients had anemia, thrombocytopenia, hyponatremia,
      hypoproteinemia, hypoalbuminemia, hypocalcemia and acute renal failure, in one
      case associated with anuria. A low grade parasitemia was observed in two patients
      and a high grade parasitemia (20%-58% of erythrocytes) in four. Exchange
      transfusion was performed only in high parasitemic patients and all of them
      survived. All patients were treated with quinine, a sulfonamide and
      pyrimethamine. Additionally, five patients received oxytetracycline, doxycycline
      or clindamycin. Three patients required hemodyalisis. Five patients had delirium,
      coma or seizures. All patients had at least one sign of hepatic impairment: liver
      enlargement, jaundice or increased bilirubin or aminotransferase levels. Two
      patients had spleen enlargement. Laboratory findings suggested disseminated
      intravascular coagulation in four patients. Four patients developed pulmonary
      changes and three of them required mechanical ventilation. A Swan-Ganz catheter
      was placed in four patients. In three of them (two with pulmonary edema) the
      pulmonary capillary wedge pressure was initially increased, which suggested a
      cardiogenic or hypervolemia mechanism, but soon returned to normal level. One
      patient with low grade parasitemia died because of adult respiratory distress
      syndrome after 18 days. In our series, the degree of parasitemia was not related
      to the severity of the disease.

PMID- 9774881
TI  - [Acute pain due to vinorelbine].
AB  - OBJECTIVE: To report the presence of an uncommon adverse effect, pain in the
      tumor location, during the administration of the cytostatic agent vinorelbine.
      METHOD: Twenty-seven patients with non operable relapses of epidermoid carcinomas
      of the head and neck were treated with two combinations of cytostatics: mitomycin
      c 10 mg/m2 on day 1 plus vinorelbine 25 mg/m2 on days 1, 8 and 15 in twelve
      patients or carboplatin 300 mg/m2 on day 1 plus vinorelbine 25 mg/m2 on days 1, 8
      and 15 in fifteen patients. RESULTS: Six patients had moderate/severe pain in the
      tumor location; concomitantly, one patient had chest pain. Four patients required
      major opiates. The clinical picture reverted and no patient had acute or chronic
      neurotoxicity. The readministration of vinorelbine triggered pain again, and all
      patients refused to continue the therapeutic program. CONCLUSION: Vinorelbine can
      cause pain at tumor location, a nonserious adverse effect which, nevertheless,
      prevented the continuation of therapy.

PMID- 9774882
TI  - [Monoclonal component in visceral leishmaniasis: a rare association that can lead
      to misdiagnosis].
AB  - The detection of monoclonal components is exceptional in patients with visceral
      leishmaniasis (VL). The cases are here reported of two patients with VL in a non
      endemic area and monoclonal components which posed problems for the differential
      diagnosis with other entities associated with the presence of paraproteins. The
      predominant clinical manifestations in both cases were general symptoms, fever
      and severe spleen enlargement. One patient had a monoclonal triple band in urine
      and the other several oligoclonal bands in serum. In the initial bone marrow
      aspiration smear no parasites were observed in any of the two cases but a
      remarkable plasmacytosis in one of them. The presence of increased serum titers
      of anti-Leishmania antibodies was the first demonstrative finding of VL. The
      diagnosis was confirmed with positive culture of Leishmania and therapy with
      pentavalent antimonials was successful in both cases. The different diagnostic
      possibilities are discussed and the possibility of VL is emphasized even in non
      endemic areas when monoclonal components in serum or urine specimens are found
      and consistent clinical findings are present.

PMID- 9774883
TI  - [Recurrent anaphylaxis: diagnostic approach and management].

PMID- 9774884
TI  - [Evolution of AIDS survival in Spain: effect of the inclusion of pulmonary
      tuberculosis for case definition in the protease inhibitors era].

PMID- 9774885
TI  - [Contribution of molecular techniques to the study of tuberculosis transmission].

PMID- 9774886
TI  - [Intrahospital necrotizing pneumonia].

PMID- 9774887
TI  - [Febrile picture with disseminated ulcers and plantar lesions].

PMID- 9774888
TI  - [Hemorrhagic blisters of the oral mucosa].

PMID- 9774889
TI  - [Sinusitis and pulmonary cavitation].

PMID- 9774890
TI  - [A 16-year old male with crepitant frontal tumor].

PMID- 9774891
TI  - [A 65 year-old man with leukemic reticuloendotheliosis, fever of unknown origin
      and multiorgan failure].

PMID- 9774892
TI  - [Sternal osteomyelitis and sternoclavicular arthritis of brucellar etiology].

PMID- 9774893
TI  - [Thyrotoxic periodic palsy as presentation form and relapse of Graves-Basedow
      disease in a Spanish male].

PMID- 9774894
TI  - [Thrombopenic purpura caused by tetracyclines?].

PMID- 9774895
TI  - [Rhabdomyolysis secondary to Conn's syndrome].

PMID- 9774896
TI  - [Soshin beri-beri: first case in Spain].

PMID- 9774897
TI  - [Transfusion induced malaria].

PMID- 9774898
TI  - [A national program of supplementation with megadoses of vitamin A].

PMID- 9774899
TI  - [Effect of supplementation with a massive dose of vitamin A in children 6 to 36
      months of age].
AB  - OBJECTIVE: To evaluate the impact of a single massive dose of vitamin A on the
      vitamin and iron status in children of margined urban areas in Hermosillo,
      Sonora, Mexico. MATERIAL AND METHODS: A total of 60 children received one dose of
      100,000 IU (children from 6 to 12 months) and of 200,000 IU (children from 12 to
      36 months) of retinol palmitate distributed by the Health Ministry in June, 1994.
      Serum levels of retinol, carotenoids, iron, transferrin and ferritin were
      measured at three periods: basal, after two weeks and after three months.
      RESULTS: The mean for retinol basal values was 0.7 mumol/l, after two weeks it
      was 0.97 mumol/l (p < 0.001) and after three months it was 0.83 mumol/l (p >
      0.05). When basal values were measured, 6.3% of the children showed severe
      vitamin A deficiency, which disappeared in the periods following the supplement;
      additionally, 42% showed moderate deficiency which had decreased to less than 7%
      after three months. No differences were found for serum iron and transferrin
      levels (p > 0.05), however, ferritin levels increased (p < 0.001) after three
      months indicating an improvement in iron reserves. CONCLUSIONS: Massive dose
      distribution may have an important impact on vitamin A and iron status in
      children.

PMID- 9774900
TI  - [Mortality for diarrheic disease in Mexico: problem of accessibility or quality
      of care?].
AB  - OBJECTIVE: To evaluate the access to health services and the process of care
      provided to children under five years old who died from acute diarrhea (AD).
      MATERIAL AND METHODS: In four states of Mexico, a cross-sectional study was
      carried out. Deaths from AD that occurred in the lapse of one year were included.
      Information about clinical characteristics of the illness, process of care and
      access to the health facilities were obtained through verbal autopsy. Descriptive
      analysis and comparison of data between rural and urban communities were
      performed. RESULTS: Five-hundred and fifty three deaths were analysed. Most of
      the children were not enrolled in a public care health system. The main
      children's characteristics were the following: residence in rural communities;
      age less than one year; died at home or had short illness duration. Geographic
      and economic access barriers were identified in rural areas. Oral rehydration
      salts were provided as a part of household treatment in about 75% of children.
      20% of them received non-medical care, specially from traditional healers.
      Primary medical care was provided to 60% of cases; the drawbacks of the process
      were related to a high rate of medication prescription, lack or referral to
      hospital, and lack of recommendation for a new visit in presence of alarm signs.
      Public physicians and those from rural communities prescribed oral rehydration
      therapy in a greater proportion. CONCLUSIONS: The problem of access to health
      services in rural communities was confirmed. However, low quality of care
      provided by primary level physicians was found in both rural and urban areas. We
      propose the creation of clinical teaching centers to improve the quality of the
      process of medical care as a strategy to decrease mortality due to AD.

PMID- 9774901
TI  - [Demographic aspects in indigenous communities of 3 regions of Colombia].
AB  - OBJECTIVE: To obtain demographic indicators for some indigenous communities in
      Colombia situated in three different regions of the country: the Caribbean, the
      Amazonian basin and the Andes. MATERIAL AND METHODS: Demographic variables
      gathered in a KAP (knowledge, attitude and practices) survey among the indigenous
      population in 1993 and 1994 were analyzed. The survey included 11,522 Indian.
      RESULTS: 45% of the population is under age 15; overall rate of fertility is 6.5
      children per woman, and death rate in 1990 was 63.3 children per 1,000 live
      births. Life expectancy at birth was 57.8 years for women and 55.4 years for men.
      CONCLUSIONS: The indicators differ substantially from the national figures.
      Although the indigenous population seems to be undergoing a process of
      demographic transition, there are marked differences between regions, with
      significantly higher fertility and infant mortality rates for the Caribbean
      region.

PMID- 9774902
TI  - [Risk factors for cervico-uterine cancer in women in Zacatecas].
AB  - OBJECTIVE: To determine the sociodemographic characteristics and the reproductive
      and sexual behavior of participants in the Cervical Cancer Prevention and Control
      Program and to identify the risk factors for this neoplasm. MATERIAL AND METHODS:
      A case control study was performed among participants in the Cervical Cancer
      Prevention and Control Program in the state of Zacatecas. The cases consisted of
      all patients diagnosed and corroborated by histopathology with CIN III and
      invasive carcinoma of the uterine cervix (251) who were referred to the Dysplasia
      Clinic (within the same program), during 1993-1995. Controls were women randomly
      selected from the population which participates in this program, who had negative
      cervical cytology. One control was selected for each case and paired by age and
      date, simultaneous to the cervical cytology. RESULTS: Risk of cervical cancer was
      higher in women with greater number of pregnancies (more than 12 pregnancies)
      than in women with less than 3 (OR 5.2, CI 95% 2.6-10.5). This is also true of
      women with greater number of births (12 or more) who have a risk five times
      higher than women with less than 3. Beginning sexual activity at an early age was
      associated to the risk of cervical cancer; women who began their sexual activity
      after the age of 19 had a risk two times lower than those who started before the
      age of 15. The use of oral contraceptives increased the risk of cervical cancer
      in relation to the use of non-hormonal contraceptives (OR 1.9, CI 95% 1.3-3.4).
      CONCLUSIONS: In the present study, the risk factors for cervical cancer in the
      population participating in the prevention and control program were higher in
      women with high parity, who began sexual activity at an early age and/or who
      consumed oral contraceptives.

PMID- 9774903
TI  - [Prevalence of arterial hypertension and related factors in a marginated rural
      population].
AB  - OBJECTIVE: To determine the prevalence and risk factors related to systemic
      arterial hypertension (SAH) in the rural marginated population of Durango,
      Mexico. MATERIAL AND METHODS: A comparative cross-sectional study was performed
      in 627 rural communities, approximately 90% of which have 250 inhabitants or
      less. The arterial pressure and sociodemographic variables were determined.
      RESULTS: A total of 5,802 subjects were studied, 4,452 women (76.7%) and 1,350
      men (23.3%). SAH was found in 1,271 individuals (21.9%; CI 95% 20.8-23.0) of
      which 1,011 were women (22.71%; CI 95% 21.5-23.9) and 260 were men (19.26%; CI
      95% 17.2-21.4). Of the target population, 3,018 individuals (52.0%) live in
      communities of less than 250 inhabitants, 2,080 (60.9%) women and 938 (31.1%)
      men. In this group, SAH was identified in 445 cases (14.74%; CI 95% 13.5-16.0) of
      which 326 are women (15.7%; CI 95% 14.1-17.3) and 119, men (12.7%; CI 95% 10.6
      14.9). The main risk factors related to SAH were obesity, type 2 diabetes,
      alcohol and tobacco consumption. CONCLUSIONS: The prevalence of SAH in the rural
      marginated population is apparently related to the degree of development of the
      communities.

PMID- 9774904
TI  - [Mortality by poisoning in children].
AB  - OBJECTIVE: To determine the standing of mortality by poisoning in children in the
      Mexican Republic, in the years from 1979-1994. MATERIAL AND METHODS: Secondary
      sources were employed. Analyzed variables were: age, sex, year, external cause of
      trauma and poisoning according to the 9th International Classification of
      Diseases: E850-E858, E860-E869 and E905. Tendencies by specific causes were
      analyzed with a Poisson regression model and relative risk by age, sex and
      district were obtained. RESULTS: A total of 11,272 children under 15 years of age
      were recorded. The main causes were poisoning and toxic reactions caused by
      venomous plants or animals (E905); accidental poisoning by household gas or
      carbon monoxide (E868); and accidental poisoning by other drugs (E858). The
      relative risk was highest in age group < 1 year; the values were RR 29.6, CI 95%
      29.2-33.4; RR 3.47, CI 95% 2.86-4.22 and RR 31.86, CI 95% 24.8-40.9. Risk was
      similar for both sexes except for E905. The state of Aguascalientes consistently
      presented the highest risk values and the state of Nuevo Leon, the lowest.
      CONCLUSIONS: Poisoning is an important cause of child mortality. Considering that
      most of these deaths can potentially be prevented since they occur at home it is
      recommended that responsible adults can build protection into their environment
      and into the way society operates. Prevention should involve a multidisciplinary
      approach since the phenomenon has multiple causes and possible solutions.

PMID- 9774905
TI  - [Hypoglycemic activity of Bouvardia terniflora, Brickellia veronicaefolia, and
      Parmentiera edulis].
AB  - OBJECTIVE: To evaluate the hypoglycemic activity of the hexane, chloroform and
      methanol extracts of Bouvardia terniflora, Brickelia veronicaefolia and
      Parmentiera edulis. MATERIAL AND METHODS: Normal and alloxan-induced diabetic
      mice were administered these plant extracts (intraperitoneal 100, 200 and 300
      mg/kg). RESULTS: The administration of 300 mg/kg of chloroform extracts from P.
      edulis and B. terniflora and hexane from B. veronicaefolia to diabetic mice
      decreased the blood glucose levels in 43.75, 58.56 and 72.13%, respectively.
      These extracts administered to normal mice reduced blood glucose levels in 29.61,
      33.42 and 39.84%, respectively. CONCLUSIONS: The hypoglycemic effect of these
      plant extracts used in traditional medicine for diabetes treatment is confirmed.

PMID- 9774906
TI  - [Accumulation of lead in bone and its effects on health].
AB  - The adverse effects of lead have been known for long since the metal affects
      practically all organs and systems of the human body. Recently, toxic effects
      have been reported in the cardiovascular and nervous systems at lead levels
      previously considered to be secure. The main lead storage site in the body is
      bone. The toxicologic significance of this fact has been clarified only recently.
      The present study analyzes the role of lead as an endogenous source of exposure,
      as a chronic exposure biomarker and as a target organ. Recent advances to measure
      bone lead through fluorescent X-Rays are discussed. Additionally, the importance
      of bone lead from a public health perspective in places with a chronic history of
      exposure such as Mexico City, and in some occupational environments is reviewed
      with particular attention placed on reproductive age women, who are potential
      lead sources for the fetus and lactating infant.

PMID- 9774907
TI  - Paradigmatic obstacles to improving the health of populations--implications for
      health policy.
AB  - While there are promising developments in public health, most interventions (both
      at the individual and community levels) remain focused on "downstream" tertiary
      treatments or one-on-one interventions. These efforts have their origins in the
      biomedical paradigm and risk factor epidemiology and the behavioral science
      research methods that serve as their handmaidens. This paper argues for a more
      appropriate balance of "downstream" efforts with a more appropriate whole
      population public health approach to health policy--what may be termed a social
      policy approach to healthy lifestyles rather than the current lifestyle approach
      to health policy. New, more appropriate research methods must be developed and
      applied to match these emerging levels of whole population intervention. We must
      avoid any disjunction between new upstream policy level interventions and the
      methods used to measure their effect--appropriate unto the intervention level
      must be the evaluation method thereof.

PMID- 9774908
TI  - [Health resources in units of the Health Secretariat, 1997].

PMID- 9774909
TI  - [Re-writing or how to move from writing to publication].

PMID- 9774910
TI  - [An editorial challenge: the publication of public health activities].

PMID- 9774911
TI  - [Good health for the residents of the community].

PMID- 9774912
TI  - [Good health according to the residents of the community].

PMID- 9774913
TI  - [A prerequisite to the development of community health: the mobilization of
      professionals and residents in Saint-Herblain].
AB  - In 1990-1991, the city of Saint-Herblain (Loire-Atlantique) has been involved in
      a method of a social development of the area. As part of it, an health project
      has been made in order to associate the residents. Through a question: "what is
      health as for you?", residents and professionals have expressed themselves about
      the neighbourhood sources before identifying the problems and difficulties. This
      "positive" method has let a dynamics to be carried out and professionals and
      inhabitants go on participating in it.

PMID- 9774914
TI  - [The IMRED (introduction, methods, results, discussion) plan is also suitable for
      reviews in education and health promotion].

PMID- 9774915
TI  - [An informative bibliography].

PMID- 9774916
TI  - [An epidemiologic study of sleep-disordered breathing in the male population of
      Lorraine: preliminary results].
AB  - The prevalence of sleep-disordered breathing (SDB) was evaluated in a male
      population sample of Lorraine (university staff), with a protocol including a
      self-completed standardized questionnaire, anthropometry (including neck, waist
      and hip circumferences) and non-invasive ear, nose, and throat examination. Among
      357 subjects present in the institution at the moment of the survey, 334 (93.6%)
      accepted to participate, and 300 (84%) returned the questionnaires. The
      anthropometric results corresponded to the French normative values according to
      gender and age. We chose a value of 32 as limit of the body mass index (BMI)
      between weight excess and obesity; this limit was exceeded by 7.2% of the
      subjects. The mean age of the sample was 44.8 (SD 10.1) years; the waist-to-hip
      ratio was of 0.907 +/- 0.053. The ENT examination found a high prevalence of
      nasal septum deviations (52.6%), of soft palate (25.2%), and uvula (42%)
      abnormalities; 32.1% of the subjects had experienced amygdalectomy. The non
      responses to the questionnaire were infrequent (less than 2%), except for the
      questions regarding a history of hypertension (2.6%), weight fluctuations the
      last 5 years (7.6%), and the number of years in school (12%). The questionnaire
      included, for each question, the optional answer "don't know"; this answer was
      chosen for the questions concerning the duration of snoring (37.1%), stopping
      breathing during sleep (12.7%) and the parental history of narcolepsy (18.7 and
      20.7%) and sleep apnoea (33.7 and 36.4%). 5.7% of the subjects declared sleep
      apnoeas at least once per week: 16.1% had unrefreshing sleep; 10.6% admitted to
      excessive daytime sleepiness; 41.9% were habitual snorers. These results indicate
      a prevalence of SDB in our sample which is comparable to the figures obtained in
      other European studies. Further analysis of our data will indicate if, besides
      weight excess and its troncular distribution, cigarette smoking and respiratory
      symptoms, the "minor" ENT abnormalities play a role in the pathogenesis of SDB.

PMID- 9774917
TI  - [Prevention priorities in mental health in Geneva: a study using the Delphi
      technic].
AB  - A Delphi technique was used to determine priorities for mental health prevention
      in Geneva. The study comprised two rounds of postal questionnaires targeted at 58
      participants concerned and/or interested by mental health through their
      association or their work. From the responses given in the first round mental
      health problems were listed, essentially health problems (65%) and service
      problems (11%) and less frequently resources problems (< 1%). Consensus produced
      in the second round indicated that 3 problems were priorities for the development
      of preventive measures: depression, alcohol abuse, maltraitance and sexual abuse.
      Using the Delphi technique, a qualitative method corresponding to a subjective
      consensus issued from a group of experts, priorities for mental health prevention
      were identified in Geneva, in 1995.

PMID- 9774918
TI  - [The campaign against AIDS in west Africa: what perspectives at the end of the
      century? From the situation of the Cote d'Ivoire as observed from the period 1987
      1997].
AB  - WHO is commissioned to create the World AIDS Program and to elaborate the
      strategy for the fight against the AIDS pandemic. The standardised strategy for
      African countries developed in Geneva in 1987 favours the prevention of sexual
      transmission of HIV without communicating the methods for such. The external and
      exclusive nature of the technical intervention of WHO and the lack of its
      adaptation to the dynamics of the epidemic in the 90s, (increase in
      seroprevalence among pregnant women, increase in the number of sick and HIV
      infected children, and economical and social consequences of the disease) explain
      in part the fact that the objectives haven't been reached on the continent a
      decade later. It seems important to us that the national authorities take
      responsibility concerning the development of an integrated strategy for AIDS
      prevention-care that takes into account the determinants of the propagation of
      the virus in Africa, advocates widespread access to testing-counselling for the
      general population and pregnant women, provides training for all health personnel
      concerning care for infected people, and promotes the implementation of social
      mechanisms for the future and financing for care, including symptomatic treatment
      for opportunistic infections.

PMID- 9774919
TI  - [Behavior linked to orodental health in 12-year-old students in the province of
      Kadiogo, Burkina Faso].
AB  - The authors present the results of a study carried out within the context of a
      diagnosis of the state of dental health among 300 twelve years old students in
      school in the province of Kadiogo (Burkina Faso). The data collected by
      questionnaires explore the range of behaviours linked to dental health: dental
      hygiene, eating habits, use of fluoride and use of dental health services. Half
      of students report that they brush their teeth at least once a day. Among them,
      there are 2 girls out of three, and one boy out of two. For half of the children,
      their mothers are the main people who teach them how to brush their teeth. For
      three children out of four, a tooth brush and tooth paste are the most common
      methods. Roughly 17% understand the usefulness of fluoride and 70% have never
      heard of it. Four children out of five consume sugared drinks on a daily basis.
      85% say they have never been to the dentist. The information collected could
      serve as a base for the development and implementation of health promotion and
      education programmes for dental health within schools.

PMID- 9774920
TI  - [Some preliminary suggestions in the implementation of evaluation studies: for
      optimal control].

PMID- 9774921
TI  - [Effect of associative strength of schema elements on intensity of startle
      reaction].
AB  - This study examined the effects of the strength of the connection between
      elements of an event schema on the surprise reaction elicited by a schema
      discrepant event sequence. The strength of the connection between schema elements
      was manipulated by the probability of an event in an event sequence given that a
      certain sequence had preceded that event. Strong connections between schema
      elements were expected to result from repeated exposure to an invariant event
      sequence. Weak connections were expected to result from repeated exposure to a
      variable event sequence. The results showed that an unexpected deviation from a
      strong connection led to a longer reaction time delay to a probe stimulus as
      compared to a deviation from a weak connection. This finding is consistent with
      the assumption that the modification of a strong connection is more effortful
      than the modification of a weak connection. Furthermore, there was a tendency
      towards higher surprise ratings when the unexpected event deviated from a strong
      connection, indicating that the discrepancy is more severe. A second experiment
      showed that the schema had changed in response to the first presentation of the
      schema-discrepant event: A second presentation of the schema-discrepant event was
      rated as less surprising and led to a shorter reaction time delay as compared to
      the first presentation. Furthermore, the results indicated that the specific
      circumstances of the first presentation are taken into account when the schema is
      changed.

PMID- 9774922
TI  - N-acetylcysteine enhances endothelium-dependent vasorelaxation in the isolated
      rat mesenteric artery.
AB  - STUDY HYPOTHESIS: Previous studies have suggested that N-acetylcysteine (NAC) may
      confer additional protection in acetaminophen (APAP) overdose by improving
      hepatic microcirculation. We hypothesize that NAC enhances release of nitric
      oxide (NO) from the vasculature. METHODS: Sprague-Dawley rat superior mesenteric
      artery rings were suspended in oxygenated Krebs-Henseleit tissue baths and
      contracted with U-46619 (a thromboxane A2-mimetic). In part 1, the effect of NAC
      on endothelial cell (EC) release of NO was assessed by measurement of
      vasorelaxation induced by acetylcholine (ACh, an EC-dependent vasorelaxor) in the
      presence and absence of NAC. In part 2, the effect of glutathione (a major
      component of NAC hepatoprotection) was examined by measuring ACh-induced
      vasorelaxation in rings from rats treated with L-buthionine sulfoxamine (BSO, a
      glutathione synthesis inhibitor). Data were analyzed by repeated-measures ANOVA.
      RESULTS: Addition of 15 to 30 mmol/L NAC after ring contraction had no direct
      vasodilatory effect. By contrast, pretreatment of rings with NAC (15 mmol/L)
      enhanced vasorelaxation induced by ACh (95.0% +/- 7.9% versus 62.3% +/- 7.6% for
      control; ACh dose, 1 mumol/L; P < .001) or by A23187, a receptor-independent, NO
      mediated vasodilator (91.6% +/- 9.6% versus 68.3% +/- 12.1% for control; A23187
      dose, 1 mumol/L; P < .001). In rings from BSO-treated rats, NAC also enhanced
      vasorelaxation (76.5% +/- 7.1%; P < .001 versus control), but to a lesser degree
      than in nontreated rats. CONCLUSION: NAC enhances endothelium-dependent
      vasodilation in an isolated rat mesenteric artery ring preparation. In addition
      to its antioxidant effects, NAC may decrease APAP hepatotoxicity by stimulating
      NO production and improving microvascular circulation.

PMID- 9774923
TI  - Emergency removal of football equipment: a cadaveric cervical spine injury model.
AB  - STUDY OBJECTIVE: To determine the influence of football helmet and shoulder pads,
      alone or in combination, on alignment of the unstable cervical spine. METHODS:
      The alignment of the intact cervical spine in 8 cadavers was assessed
      radiographically under 4 different football equipment conditions: (1) no
      equipment, (2) helmet only, (3) helmet and shoulder pads, and (4) shoulder pads
      only. Each specimen was then surgically destabilized at C5-C6 to simulate a
      flexion-distraction injury. Repeat radiographs were obtained under the same 4
      equipment conditions, and alignment of the unstable segment was analyzed.
      RESULTS: Before the destabilization, neutral alignment was maintained when both
      helmet and shoulder pads were in place. The "helmet only" condition caused a
      significant decrease in lordosis (mean, 9.6 +/- 4.7 degrees), whereas the
      "shoulder pads only" condition caused increased lordosis (13.6 +/- 6.3 degrees).
      After destabilization, the "helmet-only" condition demonstrated significant mean
      increases in C5-C6 forward angulation (16.5 +/- 8.6 degrees), posterior disc
      space height (3.8 +/- 2.3 mm), and dorsal element distraction (8.3 +/- 5.4 mm).
      CONCLUSION: Our flexion-distraction model demonstrated that immobilization of the
      neck-injured football player with only the helmet in place violates the principle
      of splinting the cervical spine in neutral alignment. By extrapolation to an
      extension-type injury, immobilization with only the shoulder pads left in place
      similarly violates this principle. In order to maintain a neutral position and
      minimize secondary injury to the cervical neural elements, the helmet and
      shoulder pads should be either both left on or both removed in the emergency
      setting.

PMID- 9774924
TI  - Patterns of injury in belted and unbelted individuals presenting to a trauma
      center after motor vehicle crash: seat belt syndrome revisited.
AB  - STUDY OBJECTIVE: Investigators have described a "seat belt syndrome" consisting
      variously of injuries to the lumbar or cervical spine, abdominal contents, or all
      3. In this study we sought to identify these and any other patterns of injury
      associated with seat belt use in patients who presented to a trauma center after
      a motor vehicle crash. METHODS: The charts of all patients involved in motor
      vehicle crashes who presented as trauma alerts to the study institution between
      January 1, 1991, and December 31, 1993, were retrospectively reviewed for data
      regarding belt use and 35 specific injuries in 7 body regions. We calculated the
      positive likelihood ratio of injury between belted and unbelted patients, along
      with 95% confidence intervals. RESULTS: We identified 1,124 patients involved in
      motor vehicle crashes. Of these subjects, 376 were belted and 544 unbelted; in
      204 belt status was unknown. Belted patients were more likely to have sustained
      sternal fracture than were unbelted patients (4% versus .7%; positive likelihood
      ratio, 1.97; 95% confidence interval, 1.09 to 3.29) but were less likely to have
      sustained head injury (30.6% versus 46.0%; positive likelihood ratio, .67; 95%
      confidence interval, .53 to .83). We noted no statistically significant
      differences in the rates of other specific injuries, including cervical and
      lumbar fractures and the need for abdominal surgery. CONCLUSION: Severe injuries
      of all types occur in both belted and unbelted individuals involved in motor
      vehicle crashes who present to a typical trauma center. With the exception of
      sternal fractures, injuries previously associated with the seat belt syndrome
      occurred in similar proportions of belted and unbelted patients. Head injuries
      were less frequent. Seat belt use cannot serve as a discriminator for specific
      injury. A diligent search of all body regions is indicated in both belted and
      unbelted patients.

PMID- 9774925
TI  - Epidemiologic features of facial injuries among motorcyclists.
AB  - STUDY OBJECTIVE: To describe the extent, nature, and severity of facial injuries
      among motorcyclists injured in a crash requiring hospital treatment. METHODS: The
      study population consisted of 5,790 motorcycle riders who sustained a nonfatal
      crash injury during 1991, 1992, or 1993 in 10 California counties. The injured
      riders were identified in 28 hospitals during 1991 and 1992 and in 18 of these 28
      hospitals in 1993. Information was collected from crash reports and hospital
      records. All injuries were coded according to the 1990 Abbreviated Injury Scale.
      RESULTS: Facial injury was present in 24.3% of injured riders, a high proportion
      of them young men. Among riders wearing helmets, 36.8% had facial injuries,
      compared with 53.8% of those not wearing helmets. Soft tissue injuries and facial
      fractures were present in 72% and 22% of the injured, respectively. The maxilla
      (22%), orbit (16%), and nasal (16%) bones were the most frequently fractured
      facial bones. The frequency of multiple facial injuries, severity of facial
      injuries, and incidence of high-severity facial fractures was greater among
      nonhelmeted riders compared with helmeted riders. Upper facial fractures were
      more common among riders without helmets compared with those wearing helmets.
      CONCLUSION: This study provides evidence of the protective value of helmets to
      reduce risk of facial injury. Information on the positive effect of facial injury
      sparing provided by helmet use should be incorporated into helmet promotion
      programs.

PMID- 9774926
TI  - Inconsistency of emergency department triage. Emergency Department Operations
      Research Working Group.
AB  - STUDY OBJECTIVE: To measure the interrater and intrarater agreement of existing
      emergency department triage systems. METHODS: This 2-phase experimental study of
      triage nurses' and EMTs ratings for 5 scripted patient scenarios used in-person
      interviews and follow-up written surveys. RESULTS: Eighty-seven participants (>
      90% of those eligible) with 55 (63%) completed both phases of the study.
      Interrater agreement on triage category was poor (kappa = .347 overall). Only 13
      of 55 (24%) participants rated the 5 cases the same severity in both phases;
      Kendall correlation (iota-B) comparing phases 1 and 2 varied from .145 to .554.
      Estimates of admission probability varied widely. Estimates of the appropriate
      time to physician evaluation (from immediate to 24 hours) was often incongruous
      with severity ratings (e.g., 54% of those participants rating a case the lowest
      severity recommended evaluation within 8 hours). There was good agreement on
      estimated need for an ED monitored bed or diagnostic studies. CONCLUSION: Triage
      assessments (both interrater and intrarater) by experienced personnel are
      inconsistent using these 5 standardized patient scenarios. These results
      challenge the reliability of current ED triage practice.

PMID- 9774927
TI  - Effectiveness of a 2-specialty, 2-tiered triage and trauma team activation
      protocol.
AB  - STUDY OBJECTIVE: To determine the effectiveness, safety, and resource allocation
      of a 2-specialty, 2-tiered triage and trauma team activation protocol. METHODS:
      We conducted a 6-month retrospective analysis of a 2-specialty, 2-tiered trauma
      team activation system at an urban Level I trauma center. Based on prehospital
      data, patients with a high likelihood of serious injury were assigned to triage
      category 1 and patients with a low likelihood of serious injury were assigned to
      category 2. Category 1 patients were immediately evaluated by both emergency
      medicine and trauma services. Category 2 patients were evaluated initially by
      emergency medicine staff with a mandatory trauma service consultation. Main
      outcomes measured included mortality, need for emergency procedures, need for
      emergency surgery, complications, and discharge disposition. Potential physician
      hours saved were calculated for category 2 cases. RESULTS: Five hundred sixty-one
      patients were assigned a triage classification (272 to category 1 and 289 to
      category 2). Category 1 patients had a higher mortality rate (95% confidence
      interval [CI] for difference of 15.9%, 11.1% to 20.7%, P < .0001), need for
      emergency surgery (10.7% versus 1.4%, 95% CI for difference of 9.3%, 5.2% to
      13.4%; P < .0001), need for emergency procedures (89% of total procedures, 95% CI
      83% to 95%; P < .0001), and discharges to rehabilitation facilities (95% CI for
      difference of 15.1%, 9.3% to 21.0%; P < .0001). The 2-tiered response system
      saved an estimated 578 physician-hours of time for the trauma service over the
      study period. CONCLUSION: This evaluation tool effectively predicts likelihood of
      serious injury, mortality, need for emergency surgery, and need for
      rehabilitation. Patients with a low likelihood of serious injury may be initially
      evaluated by the emergency medicine service effectively and safely, thus allowing
      more efficient use of surgical personnel.

PMID- 9774928
TI  - Comparison of 2 cricothyrotomy techniques: standard method versus rapid 4-step
      technique.
AB  - STUDY OBJECTIVE: To compare the success rate, complication rate and time required
      for the rapid 4-step technique versus the standard technique for cricothyrotomy.
      METHODS: We conducted a prospective, randomized crossover study. Twenty-seven
      emergency medicine interns, 1 junior medicine resident, and 4 senior medical
      students, without prior cricothyrotomy experience, were randomly divided into 2
      groups. Group 1 was initially instructed in and then performed the standard
      technique; group 2 was initially instructed in and then performed the rapid 4
      step technique. Each group was then instructed in and performed the alternate
      method. Cricothyrotomies were performed on preserved human cadavers. RESULTS: A
      surgical airway was established in 28 of 32 attempts with the use of the rapid 4
      step technique (88%); the average time elapsed before tube placement was 43
      seconds. Thirty of 32 attempts involving the standard technique (94%) were
      successful; the average time to tube placement was 134 seconds (95% confidence
      interval for a difference of 91 seconds, 63 to 119; P < .001). Complications were
      identified in 12 attempts involving the standard technique (38%; 1 considered
      major) and in 12 involving the rapid four-step technique (38%; 3 considered
      major). The incidence of major complications was 6% higher for the rapid 4-step
      technique (95% confidence interval, -9% to 21%). CONCLUSION: In a group of
      inexperienced subjects working on a preserved human cadaver model, the rapid 4
      step technique for cricothyrotomy was performed in about one third the time
      required for performance of the standard technique. This finding was both
      clinically and statistically significant. Although the 2 techniques had similar
      success and complication rates, we noted a trend toward more severe complications
      in the rapid 4-step technique.

PMID- 9774929
TI  - Outcome from out-of-hospital cardiac arrest caused by nonventricular arrhythmias:
      contribution of successful resuscitation to overall survivorship supports the
      current practice of initiating out-of-hospital ACLS.
AB  - STUDY OBJECTIVE: Studies indicate that ventricular tachycardia (VT) and
      ventricular fibrillation (VF) are no longer the most common rhythms initially
      documented in out-of-hospital sudden cardiac death. Although the outcome from
      asystole and rhythms designated as pulseless electrical activity (PEA) is
      reported as poor (approximately 1% survival), resuscitative efforts for these
      patients are still encouraged. The purpose of this study was to determine the
      potential contribution that this patient group makes to overall survivorship.
      METHODS: During this 2-year prospective study, all patients in cardiopulmonary
      arrest who were transported to the study institution after out-of-hospital
      Advanced Cardiac Life Support (ACLS) interventions were considered eligible for
      inclusion. Patients younger than 18 years of age and those in posttraumatic
      arrest were excluded. Age, sex, first-documented arrest rhythm, presence of a
      witness to the arrest, performance of bystander CPR, survival to hospital
      discharge, and functional status at discharge were recorded. RESULTS: A total of
      197 patients met the inclusion criteria. The initial rhythm was VF/VT in 59 (30%;
      95% confidence interval [CI], 24% to 37%) and asystole/PEA in 138 (70%; 95% CI,
      64% to 76%). There was 1 hospital survivor in the VT/VF group; 9 patients (7%;
      95% CI, 4% to 13%) in the asystole/PEA group survived to hospital discharge. Of
      the asystole/PEA survivors, 100% (95% CI, 66% to 100%) had a witnessed arrest and
      56% (95% CI, 21% to 86%) received bystander CPR. Fifty-six percent (95% CI, 21%
      to 86%) of the asystole/PEA survivors were discharged at a functional level
      equivalent to that preceding arrest. CONCLUSION: In this study, patients in
      asystole/PEA comprised 90% of the survivors. The outcome for patients with
      asystole/PEA whose arrest was witnessed and who received bystander CPR may be
      greater than previously estimated and supports the current practice of initiating
      aggressive out-of-hospital ACLS in this patient group.

PMID- 9774930
TI  - Survey of out-of-hospital emergency intubations in the French prehospital medical
      system: a multicenter study.
AB  - STUDY OBJECTIVE: To determine the clinical characteristics of endotracheal
      intubation in the French emergency prehospital medical system and compare these
      data with those of other systems. METHODS: This study was performed in lle de
      France (Paris Region) in mobile ICUs staffed by physicians. This prospective,
      descriptive study involved completion of a questionnaire by the operator just
      after endotracheal intubation was performed. RESULTS: Six hundred eighty-five
      (99.1%) of 691 consecutive prehospital intubations were performed successfully in
      the field. The orotracheal route was used in 96.0%, and no surgical approaches
      such as cricothyroidotomy were used. Mechanical complications occurred in 84
      patients, at a rate of 15.9% for nonarrest patients and 8.1% for arrest patients.
      A wide variety of sedation protocols were used. Difficult intubations (10.8%)
      were comparable in incidence to the number seen in US emergency departments, not
      US prehospital systems. By the same token, intubation success rates (99.1%) were
      comparable to US EDs and much higher than US prehospital results. CONCLUSION: The
      characteristics of French prehospital airway management differ significantly from
      those of other countries. These differences may be explained by differences in
      approach to prehospital management rather than differences of skill.

PMID- 9774931
TI  - Selective cervical spine radiography in blunt trauma: methodology of the National
      Emergency X-Radiography Utilization Study (NEXUS).
AB  - Fear of failure to identify cervical spine injury has led to extremely liberal
      use of radiography in patients with blunt trauma and remotely possible neck
      injury. A number of previous retrospective and small prospective studies have
      tried to address the question of whether any clinical criteria can identify
      patients, from among this group, at sufficiently low risk that cervical spine
      radiography is unnecessary. The National Emergency X-Radiography Utilization
      Study (NEXUS) is a very large, federally supported, multicenter, prospective
      study designed to define the sensitivity, for detecting significant cervical
      spine injury, of criteria previously shown to have high negative predictive
      value. Done at 23 different emergency departments across the United States and
      projected to enroll more than 20 times as many patients with cervical spine
      injury than any previous study, NEXUS should be able to answer definitively
      questions about the validity and reliability of clinical criteria used as a
      preliminary screen for cervical spine injury.

PMID- 9774932
TI  - Noninvasive ventilation: an emerging supportive technique for the emergency
      department.
AB  - Noninvasive ventilation (NIV) is the provision of ventilatory support to a
      spontaneously breathing patient without endotracheal intubation. In this review,
      we detail concerns related to endotracheal intubation and summarize the
      physiologic effects and clinical application of NIV. We then address the use of
      NIV in 5 conditions of particular interest to the practitioner of emergency
      medicine: exacerbated chronic obstructive lung disease, severe asthma, patients
      who are not candidates for endotracheal intubation, pneumonia, and pulmonary
      edema.

PMID- 9774933
TI  - Prehospital advanced life support for major trauma: critical need for clinical
      trials.
AB  - A widely diverse body of information exists on the use of Advanced Life Support
      procedures by prehospital personnel. We compared and contrasted the literature
      that currently exists on this topic. We examined methodologies, results, and
      conclusions for each article. We also stress the need for critical clinical
      evaluations in this arena.

PMID- 9774934
TI  - Resuscitations from pulseless electrical activity and asystole: how big a piece
      of the survivors' pie?

PMID- 9774935
TI  - Emergency medicine in west Kazakhstan, CIS.
AB  - Now a member of the Commonwealth of Independent States, Kazakhstan is the second
      largest of the republics that made up the former Soviet Union. This report
      describes the structure of the health care system in Kazakhstan, with particular
      emphasis on emergency medicine. It examines medical education, the organization
      of health care services, emergency medical services, emergency department
      structure, and the challenges facing emergency medicine.

PMID- 9774936
TI  - Symptomatic hypocalcemia precipitated by small-volume blood transfusion.
AB  - We present 2 cases in which the transfusion of small volumes of packed RBC was
      sufficient to precipitate symptomatic hypocalcemia. Subsequent inquiry revealed
      that both of the patients had preexisting, untreated, and asymptomatic
      hypocalcemia, 1 following partial thyroidectomy many years earlier and the other
      with documented hypocalcemia but without a definitive diagnosis.

PMID- 9774937
TI  - Aortoesophageal fistula: recognition and diagnosis in the emergency department.
AB  - An aortoesophageal fistula is a life-threatening cause of gastrointestinal
      bleeding where an abnormal communication between the esophagus and the aorta may
      result from a thoracic aortic aneurysm, foreign body ingestion, esophageal
      malignancy, or postoperative complications. The diagnosis can be made on the
      basis of clinical findings alone. Classic patients present with the triad of
      midthoracic pain, sentinel arterial hemorrhage, and exsanguination after a
      symptom-free interval (Chiari's triad). The identification of massive upper
      gastrointestinal hemorrhage that is bright red and arterial in nature is
      characteristic. Most diagnostic tests have significant individual limitations.
      Endoscopy of the upper gastrointestinal tract should exclude alternative bleeding
      sources and may show a submucosal hematoma. Aortography may be useful during
      active hemorrhage to demonstrate the fistula, but results of aortography may be
      negative during the symptom-free interval. Dynamic computed tomography may be a
      more rapid alternative. For patients who are in stable condition after the
      sentinel hemorrhage, a confirmatory test is reasonable. Patients in unstable
      condition should undergo immediate surgery. Survival is now possible with rapid
      surgical intervention.

PMID- 9774938
TI  - Intrathecal injection: unusual complication of trigger-point injection therapy.
AB  - Trigger-point injection therapy is a common procedure in primary care medicine
      and emergency medicine and is generally considered safe. A 28-year-old woman
      experienced respiratory depression and hemiplegia after the injection of a
      superficial trapezius trigger point. The patient required emergency tracheal
      intubation for ventilatory support. Computed tomography of her head revealed
      pneumocephalus. She recovered fully over the course of 24 hours. Intrathecal
      injection during a trigger-point injection is a previously unreported
      complication of trigger-point injection therapy.

PMID- 9774939
TI  - Distribution of emergency medicine residency graduates.

PMID- 9774940
TI  - National Highway Traffic Safety Administration: EMS Agenda for the Future:
      implementation guide--moving closer to the vision.

PMID- 9774941
TI  - Commentary: defining our limits.

PMID- 9774942
TI  - Laxative-induced hypokalemia.

PMID- 9774943
TI  - Ottawa ankle rules and the diabetic foot.

PMID- 9774944
TI  - Successful resuscitation of ventricular fibrillation after low-dose amiodarone.

PMID- 9774945
TI  - Tick removal.

PMID- 9774947
TI  - Trauma care systems development and evaluation. American College of Emergency
      Physicians.

PMID- 9774946
TI  - Initial management of patients who present to the emergency department with a
      work-related injury or illness. American College of Emergency Physicians.

PMID- 9774948
TI  - ACEP-recognized certifying bodies in emergency medicine. American College of
      Emergency Physicians.

PMID- 9774949
TI  - Impact of radioimmunoscintigraphy on the management of colorectal and ovarian
      cancer patients: a retrospective study.
AB  - Noninvasive differentiation of benign from malignant disease has emerged as an
      important diagnostic challenge in the current age of health-care cost
      containment. Most physicians today acknowledge that early and accurate detection
      of cancer is important in successful treatment. Antibodies have been developed,
      labeled with radioactive isotopes, and used to detect and treat malignant tumors.
      During the past few years, several radiolabeled antibodies have received approval
      from the U.S. Food and Drug Administration for imaging colorectal, lung, ovarian,
      and prostate carcinomas, thus expanding and improving the physician's ability to
      detect and follow cancer in patients. At present, there is ample evidence in the
      literature to suggest that imaging with the 111In-labeled monoclonal antibody
      B72.3 is clinically useful for detecting primary/recurrent colorectal and
      recurrent ovarian carcinomas. In this article, we present a retrospective review
      of 136 patients from 10 moderate-sized hospitals who underwent a study with
      radioimmunoscintigraphy (RIS), using the 111In B72.3 antibody and standard
      diagnostic examinations for the detection of recurrent colorectal or ovarian
      carcinoma. The resulting data were analyzed in an effort to determine if (and
      how) information obtained from this radioimmunoscintigraphic procedure is being
      used by referring physicians. Our findings suggest a gradually increasing use of
      scan findings with the 111In B72.3 antibody in making patient-management
      decisions.

PMID- 9774950
TI  - Phase II trial of paclitaxel in patients with soft-tissue sarcoma.
AB  - The response rate (RR) to single-agent chemotherapy with doxorubicin or
      ifosfamide in patients with advanced soft-tissue sarcoma (STS) is in the range of
      20%. Paclitaxel is clinically useful in treating several solid tumors and has
      demonstrated activity in a series of human sarcoma cell lines. Twenty-eight
      patients with measurable advanced STS participated in this phase II trial of
      paclitaxel at 250 mg/m2 administered as a 3-hr i.v. infusion once every 3 weeks.
      All patients received granulocyte colony-stimulating factor (G-CSF) beginning on
      the day after paclitaxel and lasting until recovery from neutropenia. No prior
      chemotherapy had been used in 17 patients; 10 patients had had prior doxorubicin
      based therapy; and 1 patient had had intraperitoneal therapy with edatrexate. Two
      partial responses (PRs) (7%; 95% confidence interval [CI] = 1-23%) were observed.
      The responding patients included a patient with angiosarcoma of the scalp who had
      complete regression of cutaneous lesions and improvement of nonmeasurable
      pulmonary disease lasting 6 months. The other PR occurred in a woman with
      metastatic uterine leiomyosarcoma and lasted 9 months. Seven patients had stable
      disease for 3-4 months. Median time to progression for all patients was 3.5
      months (range: 2.5-9 months). The mean nadir in the white-blood-cell (WBC) count
      was 3.8 x 10(3)/microliter (range: [0.2-16.2] x 10(3)/microliter), with a mean
      nadir in the absolute neutrophil count (ANC) of 2.4 x 10(3)/microliter (range:
      [0.0-7.1] x 10(3)/microliter). Three patients died while in the study. Two
      patients with angiosarcoma of the scalp who did not qualify for this study were
      treated with paclitaxel off protocol, and experienced dramatic tumor regression.
      The overall response to paclitaxel observed in this heterogeneous group of
      patients was disappointing. However, the activity seen in angiosarcoma of the
      scalp suggests that further evaluation is warranted in patients with STS.

PMID- 9774951
TI  - Chemical stability and human plasma pharmacokinetics of reduced folates.
AB  - The in vitro stability and plasma pharmacokinetics of 5,10
      methylenetetrahydrofolic acid (CH2FH4), tetrahydrofolic acid (FH4), 5
      methyltetrahydrofolic acid (CH3FH4), and 5-formyltetrahydrofolic acid (5-CHOFH4)
      were studied in view of their potential usefulness in cancer chemotherapy.
      Analysis of reduced folates was done on a high-performance liquid chromatography
      (HPLC) system. The high sensitivity of FH4 and CH2FH4 to oxidation can be
      circumvented by use of high concentrations of the folates, addition of ascorbate,
      and by thorough exclusion of atmospheric O2. Intravenous injection of 200 mg FH4
      or CH2FH4 resulted in average peak concentrations of 69.2 +/- 3.2 nmol/ml and
      46.3 +/- 2.6 nmol/ml, respectively. The plasma concentration curves support the
      concept that these highly oxygen-sensitive reduced folates can be reliably
      administered as pharmaceuticals to cancer patients through the use of a suitable
      air-occlusive system for their preparation and administration.

PMID- 9774952
TI  - Pyrazoloacridine for the treatment of hormone-refractory prostate cancer.
AB  - There is a pressing need for new agents for the treatment of hormone-resistant
      prostate cancer (HRPC). Pyrazoloacridine (PZA) has antitumor activity in several
      in vitro and in vivo tumor systems, and was selected for testing in clinical
      trials by the National Cancer Institute (NCI). We conducted a phase II trial of
      PZA for the treatment of HRPC. Seventeen male patients with HRPC were treated
      with PZA at 750 mg/m2 i.v. given over a period of 3 hr every 3 weeks. Response to
      therapy was assessed with serial measurements of serum prostate-specific antigen
      (PSA) and sequential imaging studies. The 17 patients were treated and fully
      evaluable. One patient experienced a significant decrease in PSA, from over
      10,000 ng/ml to 423 ng/ml, along with an improvement in bone scan findings.
      However, no other patient obtained an objective or PSA response (overall PSA
      response rate = 5.9%). Median survival duration was 15.3 months. Toxicity was
      moderate. If PSA is used as a marker of response, single-agent PZA appears to
      lack efficacy in the treatment of HRPC. However, the one unambiguous response,
      and the favorable toxicity profile observed, may warrant further evaluation of
      this agent.

PMID- 9774953
TI  - Multimodality therapy: radiation and continuous concomitant cis-platinum and PKC
      inhibition in a cervical carcinoma model.
AB  - The addition of chemotherapy to radiation therapy has the potential to sterilize
      micrometastases and tumor foci adjacent and peripheral to the treatment field, so
      as to enhance local control of malignancy and improve primary and salvage
      therapy. Studies were done to investigate the effects of combining cisplatin
      (CP), the most active single agent in squamous-cell cancer of the cervix, with
      irradiation and the addition of a protein kinase C (PKC) inhibitor. This initial
      report of these studies describes our experience in exposing human cervical
      carcinoma (HeLa-S3) cells grown in culture as multicellular tumor spheroids to
      continuous CP combined with radiation in an attempt to mimic both clinically
      achievable serum concentrations of CP and a weekly fractionated-dose environment.
      Radiation-dose-dependent delays of spheroid growth were not significantly
      increased in the presence of the PKC inhibitor 7-OH-staurosporine (UCN-01) at 1.0
      nM and 10.0 nM concentrations. When dose comparisons at 8 Gy alone (2 Gy x 4
      fractions) were made for combined therapy with either CP alone (1.0 microgram/ml)
      or UCN-01 alone, absolute delays in spheroid growth at the highest concentrations
      used were comparable (range: 37-41 days). Although these data alone would not
      support minimal chemotherapeutic interaction, it appears that the overall effects
      observed for combination therapy were predominately radiation-dose dependent. The
      combination of UCN-01 plus CP (0.5 and 1.0 mu/ml, respectively) was effective in
      increasing the cytostatic and cytotoxic effects of irradiation at 4 Gy (2 Gy x 2
      fractions). Observations made as early as day 4 and day 7 posttreatment were
      indicative of > or = 40% and 60%, respectively, of morphological damage. Spheroid
      growth was essentially static at these doses over the evaluation time of 60 days.
      Intracellular junctions were disorganized, and spheroid swelling was evident and
      contributed to the modest dimensional changes observed after treatment. No
      surviving fractions could be generated from spheroids that were mechanically
      disrupted, trypsinized, and plated at day 7 after the initiation of treatment. At
      2 months, 88% (14/16) and 94% (15/16) of the multimodality treatment groups (4 Gy
      + UCN-01 + CP [0.5 and 1.0 mu/ml], respectively) had sterilized spheroids,
      indicating that the CP concentration dependence may not be a sole determinant of
      efficacy. Our therapeutic strategy for combining irradiation with CP was based on
      the contemporary use of CP as the most successful agent in producing high
      survival rates in gynecological malignancy. The combination of UCN-01 with CP and
      irradiation may, however, represent a more effective strategy for enhancing
      future cisplatin-based chemotherapy regimens.

PMID- 9774954
TI  - Role of taxanes in lung-cancer chemotherapy.

PMID- 9774955
TI  - Quality of life, cancer investigation, and clinical practice.

PMID- 9774956
TI  - Molecular oncology: diagnostic and prognostic assessment of human cancers in the
      clinical laboratory.

PMID- 9774957
TI  - Opportunities for promoting palliative medicine in cancer research.

PMID- 9774958
TI  - Mechanism of action of nonsteroidal anti-inflammatory drugs.

PMID- 9774959
TI  - Aminoglycosides, vancomycin, and quinolones.

PMID- 9774960
TI  - Mechanism of action of nonsteroidal anti-inflammatory drugs.

PMID- 9774961
TI  - Access to state-of-the-art cancer treatment: should government play a role?

PMID- 9774962
TI  - Intensifying induction therapy in acute myeloid leukemia by an infusional
      chemotherapy schedule.

PMID- 9774963
TI  - Infusional chemotherapy for non-Hodgkin's lymphoma.

PMID- 9774964
TI  - New monoclonal antibodies to prevent transplant rejection.

PMID- 9774965
TI  - Lepirudin for heparin-induced thrombocytopenia.

PMID- 9774966
TI  - Brinzolamide--a new topical carbonic anhydrase inhibitor for glaucoma.

PMID- 9774967
TI  - Key roles for E2F1 in signaling p53-dependent apoptosis and in cell division
      within developing tumors.
AB  - Apoptosis induced by the p53 tumor suppressor can attenuate cancer growth in
      preclinical animal models. Inactivation of the pRb proteins in mouse brain
      epithelium by the T121 oncogene induces aberrant proliferation and p53-dependent
      apoptosis. p53 inactivation causes aggressive tumor growth due to an 85%
      reduction in apoptosis. Here, we show that E2F1 signals p53-dependent apoptosis
      since E2F1 deficiency causes an 80% apoptosis reduction. E2F1 acts upstream of
      p53 since transcriptional activation of p53 target genes is also impaired. Yet,
      E2F1 deficiency does not accelerate tumor growth. Unlike normal cells, tumor cell
      proliferation is impaired without E2F1, counterbalancing the effect of apoptosis
      reduction. These studies may explain the apparent paradox that E2F1 can act as
      both an oncogene and a tumor suppressor in experimental systems.

PMID- 9774968
TI  - Mutation of E2f-1 suppresses apoptosis and inappropriate S phase entry and
      extends survival of Rb-deficient mouse embryos.
AB  - Mice mutant for the Rb tumor suppressor gene die in mid-gestation with defects in
      erythropoiesis, cell cycle control, and apoptosis. We show here that embryos
      mutant for both Rb and its downstream target E2f-1 demonstrate significant
      suppression of apoptosis and S phase entry in certain tissues compared to Rb
      mutants, implicating E2f-1 as a critical mediator of these effects. Up-regulation
      of the p53 pathway, required for cell death in these cells in Rb mutants, is also
      suppressed in the Rb/E2f-1 double mutants. However, double mutants have defects
      in cell cycle regulation and apoptosis in some tissues and die at approximately
      E17.0 with anemia and defective skeletal muscle and lung development,
      demonstrating that E2F-1 regulation is not the sole function of pRB in
      development.

PMID- 9774969
TI  - p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating,
      death-inducing, and dominant-negative activities.
AB  - We describe the cloning of p63, a gene at chromosome 3q27-29 that bears strong
      homology to the tumor suppressor p53 and to the related gene, p73. p63 was
      detected in a variety of human and mouse tissues, including proliferating basal
      cells of epithelial layers in the epidermis, cervix, urothelium, and prostate.
      Unlike p53, the p63 gene encodes multiple isotypes with remarkably divergent
      abilities to transactivate p53 reporter genes and induce apoptosis. Importantly,
      the predominant p63 isotypes in many epithelial tissues lack an acidic N terminus
      corresponding to the transactivation domain of p53. We demonstrate that these
      truncated p63 variants can act as dominant-negative agents toward transactivation
      by p53 and p63, and we suggest the possibility of physiological interactions
      among members of the p53 family.

PMID- 9774970
TI  - Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor
      genes in mitotic and meiotic cells.
AB  - BRCA1 and BRCA2 account for most cases of familial, early onset breast and/or
      ovarian cancer and encode products that each interact with hRAD51. Results
      presented here show that BRCA1 and BRCA2 coexist in a biochemical complex and
      colocalize in subnuclear foci in somatic cells and on the axial elements of
      developing synaptonemal complexes. Like BRCA1 and RAD51, BRCA2 relocates to PCNA+
      replication sites following exposure of S phase cells to hydroxyurea or UV
      irradiation. Thus, BRCA1 and BRCA2 participate, together, in a pathway(s)
      associated with the activation of double-strand break repair and/or homologous
      recombination. Dysfunction of this pathway may be a general phenomenon in the
      majority of cases of hereditary breast and/or ovarian cancer.

PMID- 9774971
TI  - A suppressor of two essential checkpoint genes identifies a novel protein that
      negatively affects dNTP pools.
AB  - In Saccharomyces cerevisiae, MEC1 and RAD53 are essential for cell growth and
      checkpoint function. Their essential role in growth can be bypassed by deletion
      of a novel gene, SML1, which functions after several genes whose overexpression
      also suppresses mec1 inviability. In addition, sml1 affects various cellular
      processes analogous to overproducing the large subunit of ribonucleotide
      reductase, RNR1. These include effects on mitochondrial biogenesis, on the DNA
      damage response, and on cell growth. Consistent with these observations, the
      levels of dNTP pools in sml1 delta strains are increased compared to wild-type.
      This effect is not due to an increase in RNR transcription. Finally, both in vivo
      and in vitro experiments show that Sml1 binds to Rnr1. We propose that Sml1
      inhibits dNTP synthesis posttranslationally by binding directly to Rnr1 and that
      Mec1 and Rad53 are required to relieve this inhibition.

PMID- 9774972
TI  - Wrapping of promoter DNA around the RNA polymerase II initiation complex induced
      by TFIIF.
AB  - The formation of the RNA polymerase II (Pol II) initiation complex was analyzed
      using site-specific protein-DNA photo-cross-linking. We show that the RAP74
      subunit of transcription factor (TF) IIF, through its RAP30-binding domain and an
      adjacent region necessary for the formation of homomeric interactions in vitro,
      dramatically alters the distribution of RAP30, TFIIE, and Pol II along promoter
      DNA between positions -40 and +26. This isomerization of the complex, which
      requires both TFIIF and TFIIE, is accompanied by tight wrapping of the promoter
      DNA for almost a full turn around Pol II. Addition of TFIIH enhances photo-cross
      linking of Pol II to a number of promoter positions, suggesting that TFIIH
      tightens the DNA wrap around the enzyme. We present a general model to describe
      transcription initiation.

PMID- 9774973
TI  - Analysis of an activator:coactivator complex reveals an essential role for
      secondary structure in transcriptional activation.
AB  - Ser-133 phosphorylation of CREB within the kinase-inducible domain (KID) promotes
      target gene activation via complex formation with the KIX domain of the
      coactivator CBP. Concurrent phosphorylation of CREB at Ser-142 inhibits
      transcriptional induction via an unknown mechanism. Unstructured in the free
      state, KID folds into a helical structure upon binding to KIX. Using site
      directed mutagenesis based on the NMR structure of the KID:KIX complex, we have
      examined the mechanisms by which Ser-133 and Ser-142 phosphorylation regulate
      CREB activity. Our results indicate that phospho-Ser-133 stablizes whereas
      phospho-Ser-142 disrupts secondary structure-mediated interactions between CREB
      and CBP. Thus, differential phosphorylation of CREB may form the basis by which
      upstream signals regulate the specificity of target gene activation.

PMID- 9774974
TI  - Crystal structure of an octameric RuvA-Holliday junction complex.
AB  - Holliday junctions occur as intermediates in homologous recombination and DNA
      repair. In bacteria, resolution of Holliday junctions is accomplished by the
      RuvABC system, consisting of a junction-specific helicase complex RuvAB, which
      promotes branch migration, and a junction-specific endonuclease RuvC, which nicks
      two strands. The crystal structure of a complex between the RuvA protein of M.
      leprae and a synthetic four-way junction has now been determined. Rather than
      binding on the open surface of a RuvA tetramer as previously suggested, the DNA
      is sandwiched between two RuvA tetramers, which form a closed octameric shell,
      stabilized by a conserved tetramer-tetramer interface. Interactions between the
      DNA backbone and helix-hairpin-helix motifs from both tetramers suggest a
      mechanism for strand separation promoted by RuvA.

PMID- 9774975
TI  - Migration of a Holliday junction through a nucleosome directed by the E. coli
      RuvAB motor protein.
AB  - Chromatin plays a critical role in regulating access to DNA by proteins that
      direct recombination and repair. The E. coli RuvAB protein complex promotes
      branch migration of the Holliday junction recombination intermediate. The ability
      of RuvAB to negotiate passage of the junction through nucleosomal DNA is
      examined. The model system involves the formation of a Holliday junction
      positioned upstream of a nucleosome. Unassisted, the junction is blocked by a
      histone octamer. In the presence of RuvAB and ATP, rapid branch migration through
      the nucleosome is observed. It results in disruption of the histone-DNA
      interactions leading to the removal of the octamer from the junction
      intermediate. These results suggest that eukaryotic DNA motor proteins analogous
      to RuvAB could function during recombination to promote branch migration through
      chromatin.

PMID- 9774976
TI  - IRP-1 binding to ferritin mRNA prevents the recruitment of the small ribosomal
      subunit by the cap-binding complex eIF4F.
AB  - Binding of iron regulatory proteins (IRPs) to IREs located in proximity to the
      cap structure of ferritin H- and L-chain mRNAs blocks ferritin synthesis by
      preventing the recruitment of the small ribosomal subunit to the mRNA. We have
      devised a novel procedure to examine the assembly of translation initiation
      factors (eIFs) on regulated mRNAs. Unexpectedly, we find that the cap binding
      complex eIF4F (comprising eIF4E, eIF4G, and eIF4A) assembles even when IRP-1 is
      bound to the cap-proximal IRE. This assembly is futile, because bridging
      interactions between eIF4F and the small ribosomal subunit cannot be established
      in the presence of IRP-1. Our findings provide insight into translational control
      by an mRNA binding protein at the level of translation initiation factors and
      uncover a key regulatory step in iron homeostasis.

PMID- 9774977
TI  - ASK1 is essential for JNK/SAPK activation by TRAF2.
AB  - Tumor necrosis factor (TNF)-induced activation of the c-jun N-terminal kinase
      (JNK, also known as SAPK; stress-activated protein kinase) requires TNF receptor
      associated factor 2 (TRAF2). The apoptosis signal-regulating kinase 1 (ASK1) is
      activated by TNF and stimulates JNK activation. Here we show that ASK1 interacts
      with members of the TRAF family and is activated by TRAF2, TRAF5, and TRAF6
      overexpression. A truncated derivative of TRAF2, which inhibits JNK activation by
      TNF, blocks TNF-induced ASK1 activation. A catalytically inactive mutant of ASK1
      is a dominant-negative inhibitor of TNF- and TRAF2-induced JNK activation. In
      untransfected mammalian cells, ASK1 rapidly associates with TRAF2 in a TNF
      dependent manner. Thus, ASK1 is a mediator of TRAF2-induced JNK activation.

PMID- 9774978
TI  - Loss of CFTR chloride channels alters salt absorption by cystic fibrosis airway
      epithelia in vitro.
AB  - Cystic fibrosis (CF) is caused by the loss of functional CFTR Cl- channels.
      However, it is not understood how this defect disrupts salt and liquid movement
      in the airway or whether it alters the NaCl concentration in the thin liquid film
      covering the airway surface. Using a new approach, we found that CF airway
      surface liquid had a higher NaCl concentration than normal. Both CF and non-CF
      epithelia absorbed salt and liquid; however, expression of CFTR Cl- channels was
      required for maximal absorption. Thus, loss of CFTR elevates the salt
      concentration in CF airway surface liquid and in sweat by related mechanisms; the
      elevated NaCl concentration is due to a block in transcellular Cl- movement. The
      high NaCl may predispose CF airways to bacterial infections by inhibiting
      endogenous antibacterial defenses.

PMID- 9774979
TI  - Purification of glucosyltransferases (GtfB/C and GtfD) from mutant strains of
      Streptococcus mutans.
AB  - Streptococcus mutants constitutively expresses three glucosyltransferases (GTFs),
      i.e., GtfB, GtfC, and GtfD, which synthesize glucan polymers from sucrose. Two
      genetically constructed mutants of S. mutans which stably expressed either the
      cell-associated or the extracellular GTFs were selected for purification and
      characterization of these enzymes. The cell-associated GtfB and GtfC from strain
      GS-5DD lacking the gtfD gene expression were extracted by urea, renatured by
      dialysis in sodium phosphate buffer and then separated from the other wall
      associated components by column chromatography. The extracellular GtfD was
      purified from the culture supernatant of strain NHS1 lacking gtfB and gtfC gene
      expression. The molecular weights of the purified GTFs was similar (150-160 kDa),
      as determined by SDS-polyacrylamide gel electrophoresis. The GtfB/C preparation
      synthesized primarily water-insoluble glucan in a primer independent manner.
      However, the presence of the dextran enhanced the enzymatic activities of the
      GtfB/C. GtfD synthesized water-soluble glucan exclusively in a primer dependent
      manner. Purified GtfD had a pH optimum of 5.5, and a K(m) value of 4.35 mM for
      sucrose. These results indicated that the mutated strains served as an efficient
      and specific host to obtain native GTFs.

PMID- 9774980
TI  - A method of stimulating an immune response with a hapten immobilized on a
      nitrocellulose membrane.
AB  - Hapten refers to a chemical compound of small molar mass (typically less than
      1000 daltons) that can bind with an antibody, but cannot initiate an immune
      response by itself unless it is conjugated to a protein carrier of larger molar
      mass. A novel method to prepare a hapten to generate anti-hapten immunity without
      covalent conjugation to a carrier was developed. Coating both water-soluble and 
      insoluble haptens onto a nitrocellulose membrane effectively presented haptens to
      the system and caused the generation of specific anti-hapten B lymphocytes and
      antibodies by immunization both in vitro and in vivo. This method has a potential
      to substitute for conventional hapten carrier conjugation to generate anti-hapten
      immunity.

PMID- 9774981
TI  - Morphogenesis, biomass and oxytetracycline production of Streptomyces rimosus in
      submerged cultivation.
AB  - The minimal concentration of adenosine triphosphate (ATP) which could be detected
      with spectrophotometry, HPLC and luciferin-luciferase methods was 1.0 microM, 3.3
      microM and 100 nM, respectively. In submerged cultivation, most Streptomyces
      rimosus TM-55 was in hyphae fragment form at 65 h, became short-rod mycelia at
      166 h, and lysed at 504 h incubation. The ATP content had maximal value at 24 h,
      then gradually decreased during cultivation. The oxytetracycline potency
      increased as incubation occurred, had maximal potency 178.9 micrograms/ml at 166
      h, and then gradually decreased. Morphogenesis was very important in
      oxytetracycline production in submerged cultivation of Streptomyces; short-rod
      mycelia had high oxytetracycline production.

PMID- 9774982
TI  - Immunity to diphtheria in children three-to-six year of age in four counties of
      Taiwan.
AB  - An immunization program against diphtheria has been implemented in Taiwan since
      1955, using combined diphtheria, pertussis and tetanus (DPT) vaccine. Diphtheria
      immunoglobulin (DIG) level was assessed in serum samples obtained from 1138
      children, aged 3-6 years from north, south, east and central part of Taiwan by
      the VERO cell neutralization method. Specimens were collected by simple random
      sampling of residents from Hsinchu, Taichung, Pingtung and Hwalien counties,
      including both aborigines and non-aborigines. The former lived in one or two
      villages in each county, and the latter lived in a single village next to the
      former. Ninety-five percent (1086/1138) had a DIG titre > or = 0.01 IU/ml. There
      was no significant difference by sex, or by residential area. Seventy-nine
      percent (901/1138) of the children had completed the primary immunization
      schedule (at the age of 2, 4, 6 and 18 months), and the prevalence of DIG titre >
      or = 0.1 IU/ml considered to be long-term protective was as follows: 74.6% for 3
      year group; 74.5% for 4-year group; 67.9% for 5-year group; 84.7% for 6-year
      group (including 52.2% who had had a booster shot at early primary school). These
      findings show that the diphtheria vaccination program provides good immunity in
      childhood.

PMID- 9774983
TI  - [Studies on the susceptibility of two northern Taiwan strains of Aedes albopictus
      mosquitoes to Japanese encephalitis virus].
AB  - Aedes albopictus is a dominant mosquito species in northern Taiwan. In
      laboratory, the vector competence of 2 geographical strains of Aedes albopictus
      mosquitoes to NT 113 strain of Japanese encephalitis virus was examined. The
      mosquito infection dose50 (MI-D50) of Sanhsia (SH) strain by intrathoracic (i.t.)
      inoculation was shown to be -1.1 log WMICLD50 (weanling mice intracerebrum lethal
      dose), while that of Yungho (YH) strain was -2.0 log WMICLD50. The infection dose
      for 50% mosquitoes transmission (MTID50) by i.t. inoculation was 3.5 log with SH
      strain but no transmission occurred with YH strain. By feeding sweetened blood
      virus mixture, the MID50 with SH strain was 2.7 log though YH strain did not
      attain 50% infection rate. By viremic mouse blood feeding, the highest infection
      rate for both strains was about 30%. No evidence of virus transmission was
      demonstrated by oral infection.

PMID- 9774984
TI  - [Coagulase type and antimicrobial susceptibility of Staphylococcus aureus
      isolated from various areas in Taiwan].
AB  - A total of 129 strains of Staphylococcus aureus, isolated from clinical specimens
      in Taiwan between February 1992 and December 1993, were subjected to coagulase
      typing and susceptibility testing to 21 kinds of antimicrobial agents using Pasco
      MIC Gram-positive panels. In the determination of minimum inhibition
      concentration (MIC), there were 94 strains (72.9%) resistant to penicillin and
      ampicillin, 54 strains (41.9%) resistant to tetracycline and erythromycin, and 21
      strains (16.3%) resistant to oxacillin (oxacillin-resistant S. aureus; ORSA), but
      none of them was resistant to vancomycin or nitrofurantoin. As the susceptibility
      of the isolates from four different geographic districts was compared, no
      statistical difference was found except that the resistance rate to penicillin
      and ampicillin was higher in southern Taiwan, and resistance rate to rifampin and
      gentamicin was higher in central Taiwan. The ORSA strains were all resistant to
      penicillin, ampicillin, tetracycline; 95.2% of the strains were resistant to
      gentamicin, tobramycin and erythromycin. The resistance rates to drugs tested for
      ORSA strains were statistically higher than those for OSSA strains except
      vancomycin, nitrofurantoin, trimethoprim/sulfamethoxazole and
      ampicillin/sulbactam. In the coagulase typing of 127 strains, Type IV, III and
      VII were most frequently encountered. Among the coagulase types, Type IV was
      mostly encountered in the North, the South and the East of Taiwan; Type III was
      mostly encountered in central Taiwan. Among the ORSA strains, coagulase Type III
      was most predominant (85%). In conclusion, analysis of an antibiogram is easy to
      perform and the results can provide clinicians not only with correct guides for
      patient treatment but also with a useful tool for epidemiological studies.
      However, if antibiogram and coagulase typing are carried out simultaneously,
      results will be more reliable in epidemiological studies, including nosocomial
      infection survey.

PMID- 9774985
TI  - [Survey of disease of cultural shrimp in Taiwan].
AB  - The large number of hemocytes infiltrated several abnormal tissues of kuruma
      shrimp (Penaeus japonicus), including musculature, hepatopancreas, lymphoid
      organ, gill filament and sponge tissue. In addition, there were many denatured
      hemocytes existing inside acidophilic particles and forming granules. Futhermore,
      in hepatopancreas of kuruma shrimp, a white spot baculovirus (WSBV; 40-50 x 50
      300 nm) was discovered in UH (undifferential haemocyte). The epithelium cells,
      which including stomach cuticle and underlying epidermis of exoskeletal cuticle,
      could also be infected by WSBV in another main cultural species--grass shrimp (P.
      monodon). During a period of high water temperature, with pond shrimp in normal
      condition, the CFU/ml of water bacteria rose from 10(5) to 10(7), but this number
      had decreased to 10(5) CFU/ml by the time moribund shrimp began to appear.
      Coincidentally, the total bacterial number isolated from hepatopancreas and
      musculature of moribound shrimp was over 10(5) (CFU/g) and 10(3)-10(5),
      respectively. The fauna of bacteria was taken over by the active metabolitic
      species which were represented by Vibrio species causing the pond shrimp to
      undergo either behavioral changes, such as swimming on the water surface, or
      histological changes, such as having whitish muscle color, hemocyte infiltration
      and granuloma formation etc. Pathogenetic species of Vibrio including V.
      parahaemolyticus, V. alginoly ticus V. anguillarum, V. fischery and V. damsela
      were isolated from those tissues of moribund shrimp. The main pathogens, isolated
      from musculature and hepatopancreas, were V. parahaemolyticus and V.
      alginolyticus. On the other hand there, was no bacterium could be isolated from
      the musculature of healthy shrimp and only a single species of Gram (+) coccus-
      Micrococcus--was isolated from the tissue of hepatopancreas.

PMID- 9774986
TI  - Differentiation of Vibrio vulnificus strains by an arbitrarily primed polymerase
      chain reaction.
AB  - A synthetic 17 mer oligonucleotide (5'-GTTGGGTAACGCCAGGG-3') was used as a primer
      for the arbitrarily primed polymerase chain reaction (AP-PCR) to differentiate
      various strains of Vibrio vulnificus. A total of 37 genomic DNAs that were
      extracted from the clinical and environmental strains were successfully
      differentiated. Among them, 32 profiles of the 37 strains were characterized.
      None of the environmental and clinical strains had the same amplification
      profile, suggesting the highly heterogeneous population existed in the strains of
      V. vulnificus. The size of the amplified sequences ranged from 0.3 to 2.0 Kb and
      the DNAs were separated to 12 to 20 bands by the 1.2% agarose gel. The clinical
      isolates from two independent episodes of V. vulnificus infections in a patient
      were shown to have the same profile, indicating that the second episode was due
      to recurrence rather than reinfection. The profiles of amplification were
      reproducible with different preparations of genomic DNA. Arbitrarily primed
      polymerase chain reaction can therefore be a useful tool for epidemiological
      study of V. vulnificus infection.

PMID- 9774987
TI  - Review of taeniasis in Asia.
AB  - Although Asian Taenia is closely related to T. saginata, it is a genetically
      distinct entity and can be distinguished from the classical T. saginata. Man is
      the only definite host of this parasite. The domestic pig and wild boar in Taiwan
      as well as domestic pig in Korea have been determined to be the natural
      intermediate hosts. Moreover, the pig has been demonstrated to be the most
      favorable experimental intermediate host. The cysticerci are situated mainly in
      the liver. They are smaller than T. saginata cysticerci and have a shorter
      developmental period of four weeks. The scolex of Asian Taenia cysticercus is
      often armed with two rows of hooklets. The adult worm of Asian Taenia is shorter
      and has less number of segments than the classical T. saginata. Recently, results
      of polymerase chain reaction studies indicate that the Asian Taenia is much more
      closely related to T. saginata than other taeniid species. Therefore, it is
      appropriate to designate Asian Taenia as a new subspecies of Taenia saginata
      asiatica. People in the Asian-Pacific region acquired the infection by eating raw
      or undercooked meat and/or viscera of pigs. Human experimental infections have
      succeeded in confirming the life cycle of Asian Taenia and the transmission
      pathway of the infection. In addition, multiple infection occurs very often and
      the infection has a family pattern. "Discharge of proglottids" is the most
      important clinical manifestation which is also useful in the diagnosis.
      Praziquantel is the drug of choice. The infection of Asian Taenia can be
      prevented by avoiding to eat raw or undercooked meat and viscera of pigs in the
      endemic regions.

PMID- 9774988
TI  - Clinical microbiology quality assurance program: a Taiwan experience.
AB  - Quality assurance programs have been established during the last two decades in
      developed countries to promote high quality performance in clinical laboratories.
      In Taiwan, such a program for clinical microbiology laboratories has been in
      place since July 1987. It has been supported by the Department of Health,
      Executive Yuan, R.O.C. and was set up by the authors. The manpower status,
      facilities and equipment, and performance of clinical laboratories were
      investigated during the first year and standards of laboratory quality were
      recommended. Since then, under a continuing education program, we have conducted
      seminars, symposia, workshops, short-courses or panel discussions approximately 4
      times a year. There have been about 150 participants per session and they have
      come from local hospitals (primary care hospitals), regional hospitals (secondary
      care hospitals) and medical centers (tertiary care hospitals). Proficiency test
      specimens or external unknown specimens were sent to all the laboratories twice a
      year and approximately 3 specimens were used each time for the evaluation of each
      laboratory's diagnostic capability and quality of service. Results indicated that
      there were tremendous improvements in the quality of laboratory performance. At
      the same time, several laboratory manuals describing the methods of quality
      control of clinical specimens, test procedures, media and reagents, personnel
      management and a compilation of reports etc. were published as guidelines of
      basic requirements for each level of the laboratories. For local hospital
      laboratories in remote areas, several regional hospitals or medical centers with
      high quality laboratories were selected to serve as back-ups. Our evaluation has
      shown that the performance and quality of service provided by most clinical
      microbiology laboratories in Taiwan have now reached nearly the level of those
      found in the so-called "developed countries".

PMID- 9774989
TI  - [Amylase production of Streptomyces rimosus TM-55 and their 2-deoxyglucose
      resistant mutants].
AB  - Streptomyces rimosus TM-55 was treated with 3% ethyl melthylsulfonate for 60
      minutes to generate mutants producing high amount of amylase, and 1,283 mutants
      were isolated from yeast extract starch (YS) medium containing 0.1% 2
      deoxyglucose. Amylase activity was primarily screened by clear zone formation on
      YS medium after spraying with iodine solution. Two mutants designed as D-35 and D
      62 had higher amylase activity than that of the parent strain. Amylase activity
      of the mutants in the YS broth was 2.97- and 3.45-fold of the parent strain,
      respectively. With the addition of 0.1% lactose, and 2-deoxyglucose, amylase
      activity of the mutants D-35 and D-62 was 27-73% and 4-7% higher than that of the
      parent strain. With the addition of 0.1% sucrose, amylase activity of the mutant
      D-35 was 18.37% lower than that of the parent strain. Moreover, with the
      supplement of 0.1% glucose, amylase activity of both the mutants D-35 and D-62
      was 3.67 and 3.40 fold of the parent strain.

PMID- 9774990
TI  - Isolation and identification of influenza viruses from clinical materials in 1977
      1993 at Veterans General Hospital-Taipei.
AB  - From 1977 to 1993, 15,189 throat swab samples were received for isolation and
      identification of influenza virus in the Clinical Virology Laboratory, Veterans
      General Hospital-Taipei. Most of the samples came from the Pediatric Department.
      There were 634 identified strains of the influenza virus; the successful
      isolation rate was 4.17% in average/year. Among these isolates, 56.3% (357/634)
      were influenza B; 12.1% (77/634) were influenza A/H1N1 and 28.1% (178/634) were
      influenza A/H3N2. About 3.5% (22/634) were classified as flu-like agents because
      of no reaction with available monoclonal antibodies. In recent years, reverse
      transcriptase polymerase chain reaction (RT-PCR) was established here to re
      evaluate these virus stocks. This method can provide rapid diagnosis method to
      identify influenza A/H1N1, A/H3N2 and B. Further, the RT-PCR method and
      sequencing of amplified DNA could be used to see the variation of virus isolates
      which were recirculated or which reappeared in the Taipei area.

PMID- 9774991
TI  - Generation and characterization of Japanese encephalitis virus specific
      monoclonal antibodies.
AB  - Monoclonal antibodies (MoAbs) specifically against Japanese encephalitis virus
      (JEV) were generated by fusion of immunized mouse spleen cells with NS-1 myeloma
      cells. Nakayama-NIH (Na) and three Taiwan local strains of JEV, i.e., TL isolated
      from a patient's brain in 1965, NT109 (JE7) isolated from Cx. tritaeniorhynchus
      in 1985, and RP9, a plaque purified clone of NT109, were used in the
      immunization. The specificities of moAbs were determined by immunoprecipitation
      and western blotting, using JEV-infected cell lysates. They were confirmed by the
      same methods using recombinant JEV proteins as antigens. From Na immunization, 4
      anti-E, 3 anti-NS1 and 3 anti-NS3 moAbs were generated. Seventeen anti-E, three
      anti-NS1 and three anti-NS3 specific moAbs were generated from mice immunized
      with Taiwan local JEV strains. Overall 21 anti-E, 6 anti-NS1, and 6 anti-NS3
      moAbs were produced and characterized. The isotypes of these moAbs were also
      determined and described. Interestingly, a majority of the moAbs generated for
      RP9 were IgG1 isotype. In conclusion, 33 moAbs specific to JEV were generated and
      characterized, and some of these anti-JEV moAbs were made against Taiwan local
      isolates. These moAbs provide a powerful tool to study JEV, especially the
      antigenic properties of Taiwan's local strains.

PMID- 9774992
TI  - Diminished actin polymerization of neonatal neutrophils determined by a
      microvolume whole blood method.
AB  - To investigate the actin response to chemotactic stimulation of neonatal
      neutrophils, we developed a new procedure to measure neutrophil F-actin content
      directly in microvolume whole blood (100 microliters sample each test). Using
      this procedure, we compared neutrophil actin response to N-formyl-methyonyl
      leucyl-phenylalanine (FMLP) between groups of normal neonate and adult
      volunteers. Relative F-actin content (FMLP/control ratio) of neonatal neutrophils
      is significantly lower than those of adult volunteers' neutrophils both at 30 sec
      (1.94 +/- 0.34 vs. 2.25 +/- 0.31; n = 16, p < 0.05, t test) and 60 sec (2.23 +/-
      0.19 vs. 2.40 +/- 0.27; n = 16, p < 0.05, t test) after FMLP stimulation. These
      results provide new evidence of impairment of neutrophil actin response in the
      neonate, which may partially explain the observed chemotactic defect in neonatal
      neutrophils.

PMID- 9774993
TI  - [Hemolytic disease of the newborn caused by maternal anti-Di(a): a case report in
      Taiwan].
AB  - The first case of hemolytic disease of the newborn (HDN) possibly caused by anti
      Di(a) in a Chinese infant in Taiwan is reported. The mother had two pregnancies
      before but no history of blood transfusion. Her first male infant was normal, but
      her second full-term male one developed mild jaundice soon after birth, and the
      total bilirubin level was 12.1 mg/dL, 18.3 mg/dL, 23.6 mg/dL at 24 hours, 48
      hours, and 72 hours of age, respectively. Total bilirubin was 9.1 mg/dL on the
      eighth day after receiving phototherapy and compatible blood exchange
      transfusion. The infant recovered uneventfully. The immunohematological study
      revealed that the mother was group AB, Rh (D)+; Di(a - b+), the father was group
      O, Rh (D)+; Di(a + b+), the infant boy and his 2-year-old brother were group B,
      Rh(D)+; Di(a + b+). The direct antiglobulin test (DAT) on the infant red cells
      was positive (4+ with polyspecific AHG; 4+ with anti-IgG). The maternal serum and
      infant's eluate from red blood cells showed negative reactions in routine
      antibody detection tests, but they contained alloantibody reacting against the
      Di(a+) cells by the manual polybrene test (MP) and indirect antiglobulin test
      (IAT) in AHG phase. The anti-Di(a) titers in the mother's serum was MP 1:256 and
      AHG 1:256, and in the infant's eluate was MP 1:128 and AHC 1:64 against Di(a +
      b+) cells. Based on the above results we conclude that the jaundice in this
      newborn baby was caused by maternal anti-Di(a) which was most likely induced by
      previous pregnancy. In conclusion, Diego blood group is a system of high value in
      anthropology because it accounts for the Mongoloid origin of American Indians,
      Japanese and Chinese. Anti-Di(a) may cause HDN, as in our case of HDN due to
      maternal anti-Di(a) in a Chinese infant. But in Europe and America, where
      practically all people are Di(a - b+) phenotypes, the system seems of no interest
      in parental studies as well as in blood transfusions. Owing to the Di(a) antigen
      is of higher incidence in Chinese population, we suggest that the Diego system
      should be involved in routine compatibility testing or antibody identification
      problems in parental studies and in blood transfusions in Taiwan.

PMID- 9774994
TI  - Latex agglutination test for detection of tetanus antitoxins.
AB  - A rapid and easy method of slide agglutination test for the detection of human
      tetanus antitoxins was developed in this study. Testing reagents were prepared
      from carboxylated polystyrene latex particles with tetanus toxin by soluble
      carbodiimide. The test was performed on a glass slide with a drop of test sample
      and a drop of testing reagent. The agglutination reaction was usually completed
      within five minutes. Sensitivity of this test for tetanus antitoxins can be
      reached at 0.125 IU/ml. Therefore, the latex agglutination test can be used to
      determine the immune status of a patient in an emergency.

PMID- 9774995
TI  - HLA-A, B antigens and their linkage with HLA-DR among blood donors in Taiwan.
AB  - The distribution pattern of HLA antigens varies to a great extent among different
      ethnic groups. Availability of HLA antigen distribution information is very
      important for disease association study, paternity testing and recipient/donor
      matching. Analysis of 11,383 blood donors from the Taipei Blood Center, Chinese
      Blood Services Foundation (CBSF), gave evidence that the distribution pattern of
      HLA-A,B antigens was unique, yet closer to Southern Chinese with higher A11, A33,
      B16, B40 frequencies, and B46, B48, B54 as unique antigens when compared with
      Caucasians. Pairwise linkage disequilibrium analysis between HLA-A, -B and -DR
      antigens from 238 blood donors revealed unique linkages of A33-B17, A2-B46, A11
      B15, A24-B40; A11-DR5, A2-DR9, B17-DR3, B40-DR8, B13-DR2. In addition, A33-B58
      DR3 were the most frequent 3-loci haplotypes. Knowing linkage disequilibrium
      between HLA loci and preferential association of DR specificity among various HLA
      A,B haplotypes may provide a more efficient strategy to obtain an HLA-DR or HLA-D
      region compatible unrelated bone marrow donor from an existing HLA data bank.

PMID- 9774996
TI  - Biological characteristics of human hepatocellular carcinoma cell lines with or
      without prior nude mouse passages.
AB  - A cell line, J5, derived directly from the human hepatocellular carcinoma (HCC)
      by in vitro culture, and three other lines, J2-23, J3-27 and J3-28, which were
      established in culture only after passages in nude mice were examined. Since nude
      mice as well as various strains of normal mice often produce infectious murine
      retroviruses, the HCC cells passaged as a heterotransplant in nude mice may be
      infected with these viruses. The supernatant of the J2-23, J3-27 and J3-28 cell
      co-cultured with a wild mouse cell line, SC-1, which supports the murine
      ecotropic retroviruses, showed the presence of a murine N-tropic virus. No murine
      xenotropic retrovirus was detected in these cells using S+L- mink cell assay
      method. A clone (J3-28 Clone 1) was derived from the above mentioned J3-28 cells,
      since the latter contained a mixture of human and murine cells. The J3-28 Clone 1
      was found to be entirely of human karyotype. This clone as well as the J5 and the
      PLC/PRF/5 cel lines which have never been passaged in nude mice, showed none of
      these murine retroviruses. By Southern-blot hybridization, no change was
      detectable for c-abl, c-ras, c-mos, and c-myc protooncogenes in the chromosomal
      DNA of J2-23, J3-27, J3-28 Clone 1, and J5 cell lines. The karyotypes of all the
      HCC cell lines were aneuploid, and those of the J2-23 and J3-27 cell lines were
      of mouse, while the J3-28 Clone 1 and J5 cell lines were of human. The
      chromosomes of the J2-23 and J3-27 cells showed, except for the presence of a few
      marker chromosomes in the former, no apparent changes in the length were
      observed. In contrast, those of the J3-28 Clone 1 and J5 cells exhibited various
      changes, including 6-8 marker chromosomes, and an increase or decrease in the
      length of p and/or q arms of various chromosomes.

PMID- 9774997
TI  - Evaluation of screening kits for the detection of anti-human immunodeficiency
      virus type 1 and 2 (HIV-1/2) antibodies.
AB  - HIV-1/HIV-2 3rd generation (Abbott), Wellcozyme HIV 1 + 2 (Murex), Enzygnost Anti
      HIV 1/-HIV 2 (Behring), and Genelavia Mixt (Sanofi Diagnostics Pasteur) are
      currently registered by authorities as enzyme immunoassays (EIAs) for detecting
      HIV-1/2 infection. The present study dissects these reagents by means of the
      major antigenic components, assay principles and their actual performance. The
      performances have been evaluated by their test results in international panels of
      seroconversion, mixed titer performance and HIV-1/2 combination, respectively.
      Those EIA tests were further used to examine 26 potentially false-reacting
      samples, serial diluted sera prepared from two confirmed positive specimens and
      720 specimens obtained from random blood donors in the Taipei Blood Center,
      Chinese Blood Services Foundation (CBSF). The results showed that, although
      standard sera of the mixed titer, performance and HIV-1/2 combination rows could
      not distinguish significantly among various EIAs, the seroconverting samples
      clearly showed their differences. The differences, as calculated by using 3 of 4
      seroconverting sera, was a backward window period ranging from 19 to 23 days as
      compared to the detection of HIV-1 antigens. Together, these studies strongly
      suggest that assays which are capable of detecting HIV-specific IgM and IgG
      antibodies have a shorter seroconversion window. Furthermore, the HIV-2 antigen
      seems to be crucial for successful detection of anti-HIV-2. Finally, testing anti
      HIV-1/2 in the routine screenings is expected not to increase the exclusion rate
      of blood units currently acquired from the examination of anti-HIV-1.
      Consequently, with both HIV-1/2 specificities and the ability of early detection,
      IgM/IgG-captured EIAs may represent a better screening method than assays based
      solely on the detection of HIV-specific IgG.

PMID- 9774998
TI  - In Vitro antimicrobial susceptibilities of Streptococcus pneumoniae isolated from
      two teaching hospitals in Taiwan, 1989-1995.
AB  - The susceptibility of 46 pneumococcal isolates collected during October 1989 to
      May 1995 from National Taiwan University Hospital and Taipei Municipal Yang Ming
      Hospital was studied. Among these isolates, the resistant rate of penicillin G
      was 21.7%; the penicillin G-resistant strains were more frequently resistant than
      the penicillin-sensitive strains to other beta-lactam antimicrobial drugs. The
      minimum bactericidal concentrations (MBCs) of penicillin G for all isolates were
      equal to, or one dilution higher than, minimum inhibitory concentrations (MICs).
      Three strains were false positive for penicillin resistance among isolates of
      Streptococcus pneumoniae screened with oxacillin. On the other hand, resistance
      to penicillin G was often independent of resistance to erythromycin. Vancomycin
      was the most active agent tested.

PMID- 9774999
TI  - [Secular trends in the etiology of nosocomial infection at a teaching hospital in
      Taiwan, 1981-1994].
AB  - Surveillance system of nosocomial infection was established in 1980 at the
      National Taiwan University Hospital (NTUH). To identify pathogens and the secular
      trends in the etiology of nosocomial infection from 1981 to 1994, the
      prospective, hospital-wide nosocomial surveillance data were analysed. During
      this period, 22,146 pathogens causing nosocomial infections were isolated. Gram
      negative aerobic bacteria remained the major pathogens, but gram-positive cocci
      and fungi increased rapidly in the past 14 years. When the overall pathogen
      distribution is examined, Pseudomonas areuginosa was the most frequently isolated
      pathogen, but Candida albicans and other yeasts have taken the leading position
      since 1993. Staphylococcus aureus and coagulase-negative staphylococci also
      increase significantly in recent years. When the pathogens causing infection at
      the 4 major sites were examined. P. aeruginosa was the pathogen most often
      associated with respiratory tract and surgical wound infections. In blood stream
      and urinary tract infections, we observed Escherichia coli was replaced by C.
      albicans and other yeasts as a most common isolate in these years. In addition,
      C. albicans and other yeasts and methicillin-resistant S. aureus (MRSA) are
      emerging as major nosocomial pathogens at NTUH. C. albicans and other yeast
      increased from 1.8% in 1981 to 14.9% in 1994 in the overall nosocomial infection.
      The increase was found in the blood stream (2.1% to 16.2%) and urinary tract
      infections (5.4% to 24.7%). Of 1,742 nosocomial S. aureus isolates, the
      percentage of MRSA rose from 12.5% in 1981 to 55.2% in 1994. The high percentage
      of MRSA was observed at 4 major anatomic sites of infection. In summary,
      significant shifts in the pathogens of nosocomial infection have occurred in the
      past 14 years at NTUH, and the distribution of nosocomial pathogens was similar
      to those reported in the United States in recent years.

PMID- 9775000
TI  - Evaluation of four commercial rapid diagnostic kits for identifying
      Staphylococcus aureus.
AB  - Three rapid latex agglutination kits (Aureus Test, Pastorex Staph-Plus, and
      StaphAurex) and one hemagglutination test kit (SlidexStaph) were compared with
      the conventional coagulase test for the identification of Staphyloccus aureus. A
      total of 192 methicillin-resistant S. aureus (MRSA), 75 methicillin-susceptible
      S. aureus (MSSA) and 86 coagulase-negative staphylococci and Micrococcus spp.
      were tested. The sensitivities of Aureus Test, Pastorex Staph-Plus, StaphAurex
      and SlidexStaph were 98.6, 99.4, 90.8 and 97.3%, respectively. Capsular serotypes
      of 27 strains of MRSA were also determined, in which 15 (55.6%) were capsular
      serotype 5, 11 (40.7%) were capsular serotype 8, and 1 (3.7%) was nontypeable.
      All the commercial agglutination kits showed 100% specificity except StaphAurex
      which had a specificity of only 96.5%. False-positive reactions were found in the
      strains of S. hominis, S. warneri and unidentified coagulase-negative
      staphylococci. These results suggest that Aureus Test, Pastorex Staph-Plus, and
      SlidexStaph are better than StaphAurex for rapid identification of S. aureus.

PMID- 9775001
TI  - Survey of antitrypanosome antibodies and studies of their specificity and
      autoimmunity.
AB  - As a part of investigations to characterize trypanosome infections in Taiwan,
      sera collected from patients admitted to Veterans General Hospital, Taipei were
      tested for antitrypanosome antibodies. A Trypanosoma cruzi extract-based enzyme
      linked immunosorbent assay (ELISA) was used to screen and titrate 1,297 patient
      sera. High antitrypanosome titers were detected in 166 (12.8%) of these sera.
      Retitration of random samples of the high titer (HT) sera indicated a 5.4% false
      positive. Thirteen donors with high antitrypanosome ELISA titers were followed
      up. Twelve of then remained high serum titers also showed high ELISA titers
      against an extract of Trypanosoma conorhini. Hemocultures conducted on freshly
      drawn blood specimens of the 13 subjects did not provide any evidence of
      trypanosome infections. Electrophoretic analyses of sera from HT and low titer
      (LT) patients suggested differences between serum proteins of the subjects in
      each of the groups. Atypical reactions were observed in immunodiffusion tests
      performed with HT and LT sera and trypanosome extracts, while western blot
      analyses revealed a complex pattern of binding by both sera. The qualitative and
      quantitative differences in these tests suggested interactions of T. cruzi
      antigens with donor antibodies against unrelated antigens and/or with
      autoantibodies. Subsequent analyses did not indicate any association between
      rheumatoid factor and the reactivities of the HT sera with the parasites.
      However, antinuclear antibodies were detected with an indirect fluorescent
      antibody test (IFAT) in 50% of the HT sera and 22% of the LT sera. No differences
      were found between the levels of antilaminin activity of the two groups. The IFAT
      employing T. cruzi epimastigotes was positive for 100% of the HT sera and 22% of
      the LT sera. The data indicate that the high seropositivity recognized in this
      study is due in part to the activities of cross-reacting antibodies and/or
      autoantibodies in the sample population.

PMID- 9775002
TI  - Purification and characterization of Streptococcus mutans glucosyltransferase
      (GtfC) expressed in Escherichia coli.
AB  - Streptococcus mutans constitutively expresses three glucosyltransferases, i.e.,
      GtfB, GtfC, and GtfD; which synthesize glucan polymers from sucrose. To obtain
      individual GTF without complexing with one another, a purification strategy was
      developed to recover recombinant GTF expressed from Escherichia coli. The
      recombinant GtfC was aggregated and associated with the insoluble fraction in E.
      coli homogenates. GtfC was solublized with the 8M urea, renatured to its
      biologically active form by serial dialysis against sodium phosphate buffer, and
      subsequently purified to homogeneity by DEAE-Sephacel and hydroxylapatite column
      chromatography. The GtfC enzyme preparation was purified 16.3-fold and the
      molecular weight was estimated to be 140 kDa. GtfC synthesized water insoluble
      glucan in a primer independent manner and its enzymatic activities could be
      enhanced by dextran. Purified GtfC had a pH optimum of 6.5, a K(m) of 9.26 mM for
      sucrose and a pI of 5.5. Distinct from the previous reports, results from this
      study offers an alternative for the purification of the recombinant GTFs free
      from any detergent contamination to make it more suitable for utilization in
      vivo.

PMID- 9775003
TI  - Characterization of the manganese-resistant mutants derived from Vibrio
      parahaemolyticus.
AB  - The virulence and some related factors of Vibrio parahaemolyticus are regulated
      by the level of iron. In this study, five Mn-resistant mutants were selected
      after N-methyl-N'-nitrosoguanidine treatment and two transfers in medium
      containing high levels of manganese chloride. Production of siderophores and the
      77-kDa iron-regulated outer-membrane protein and the bacterial growth in these Mn
      resistants were deregulated, as compared with the wild-type strain. In addition,
      the regulation of these phenomena was partially or completely restored by the
      introduction of Escherichia coli fur gene. Also, the total cellular protein
      profiles of the wild-type and mutants showed that production of some proteins
      were positively or negatively regulated by iron, and expression of some of these
      proteins remained unaffected in these mutants. These results suggested the
      presence of a complicated iron regulation system, similar to the Fur system of E.
      coli, in this pathogen.

PMID- 9775004
TI  - Ribotyping of clinical Vibrio vulnificus isolates.
AB  - Restriction fragment length polymorphism analysis of rRNA genes (ribotyping) was
      used to differentiate Vibrio vulnificus isolates. Among the 10 restriction
      enzymes tested, HindIII was shown to provide the most discriminatory patterns.
      Stul was used for further analysis of strains that were indistinguishable with
      HindIII. Thirteen clinical V. vulnificus strains were analyzed for their
      ribotypes with HindIII, as well as Stul when necessary. Four of the clinical
      strains were isolated from different samples collected from the same patient, and
      were shown to have identical ribotypes. All the others gave unique ribotypes,
      indicating the large genetic divergence in V. vulnificus clinical isolates. The
      ribotype of V. vulnificus by HindIII remained unchanged after successive in vitro
      and in vivo passages. HindIII gave rise to five bands which were shown in every
      V. vulnificus strain but not in other vibrio species tested, suggesting that
      ribotyping with this restriction enzyme may be useful for confirming the
      identification of this bacterium.

PMID- 9775005
TI  - Sequencing analysis of hepatitis C virus mixed genotype in a hemodialysis
      patients.
AB  - It has become clear that the genotypes of HCV vary with respect to pathogenicity,
      infectivity, response to antiviral therapy and geographic clustering. The
      prevalence of genotype distribution of HCV infection in Taiwan was investigated
      by typing with type-specific DNA primers in HCV core region. Using a design by
      Okamoto et al., it was found that in 280 serum samples examined, 3.3% (4/122) of
      the virus detected were mixed type. The implication of mixed type infection
      remains to be clarified: whether it is a single infection with a new variant, or
      infection with two HCV virions at different times or confusion with type-specific
      DNA primers themselves. The nucleotide sequences of the recombinant plasmid DNAs
      and the PCR products recovered from gel electrophoresis were analyzed by
      autosequencer. Gene sequences of HCV cDNAs of the two blood donors were used as
      control. To double check the results, we have also analyzed the DNA sequences of
      the cloned plasmids in the NS5 region with the primer system designed by Chayama
      et al. Results indicated that the hemodialysis patient was doubly infected with
      HCV, rather than by a HCV variant.

PMID- 9775006
TI  - Molecular epidemiological studies of Vibrio cholerae in Taiwan: genotyping by
      polymerase chain reaction and DNA sequencing.
AB  - To type the Vibrio cholerae strains isolated from sporadic and epidemic cases in
      Taiwan, 28 toxigenic isolates were studied by sequencing polymerase chain
      reaction-amplified cholera toxin gene (ctx) fragments. Based on specific base
      substitutions on positions 115 and 203 of ctxB and comparison with previously
      published typing system from Centers for Disease Control and Prevention (Olsvik
      theta et al., J Clin Microbiol 1993; 31:22-5, Ref.1), two genotypes were
      identified. Cholera strains from imported seafood and sporadic cases in Taiwan
      had ctxB polymorphism of genotype 1; strains from patients in the 1962 Taiwan
      epidemic and Taiwan raised soft-shell turtles had ctxB polymorphism of genotype
      3. Moreover, one toxigenic non-O1 strain was found to have other 11 different
      nucleotides in ctxB compared with those of the O1 and O139 strains. Therefore,
      DNA sequencing is a useful method for obtaining more complete genetic
      information. The approach could be improved by applying it to other more
      polymorphic regions of bacterial genome to obtain better epidemiological
      information among infected cases.

PMID- 9775007
TI  - [The toxicology and prevention of the risks of occupational exposure to aromatic
      polycyclic hydrocarbons. I. Guide lines for the prevention of the risks of
      occupational exposure to aromatic polycyclic hydrocarbons. Societa Italiana
      Valori di Riferimento and Cattedra di Medicina del Lavoro, Universita di
      Brescia].
AB  - These guidelines mainly deal with prevention of carcinogenic effects following
      occupational exposure to polycyclic aromatic hydrocarbons (PAH). After some
      toxicological remarks, the guidelines define a possible method to demonstrate and
      evaluate occupational exposure to PAH. In particular, it is illustrated the
      strategy of environmental monitoring and indicated which PAH should be measured,
      with suggestion about the most appropriate analytical techniques. As regards
      biological monitoring, the 1-OH-pyreneseems to be currently the most useful
      indicator since it reflects the recent and global exposure to PAH. The guidelines
      also give elements to interpret monitoring data, taking into account
      environmental and biological reference and limit values suggested by some
      authors, Associations, or current regulations. The most important health effects
      are carcinogenic and excess risks have been described mainly for lung, bladder
      and skin cancer in some PAH exposed workers. The studies on cytogenetic effects
      showed contradictory results. On the basis of such information and current
      regulations, the guidelines show how to perform health surveillance in preventive
      and periodical examinations and how to proceed for the information and formation
      of exposed workers. It is not advisable, on the basis of the current scientific
      data, to screen asymptomatic PAH exposed workers for early diagnosis of lung or
      bladder cancer, nor it is opportune the use of tumor markers for health
      surveillance nor is genetic screening applicable for individual susceptibility
      evaluation outside research programs.

PMID- 9775009
TI  - [The toxicology and prevention of the risks of occupational exposure to aromatic
      polycyclic hydrocarbons. III. The effects: epidemiological evidence, early
      effects. Individual hypersusceptibility. Health surveillance].
AB  - Adverse effects following occupational exposure to polycyclic aromatic
      hydrocarbons (PAH) are mainly carcinogenic. The available epidemiological data
      suggest that some substances and industrial processes, in which PAH exposure is
      frequent, are classified as carcinogenic to humans: primary aluminium industry,
      cola gasification, coke production, iron and steel foundry, coal tar, pitch,
      creosote, untreated mineral oils, asphalt, soot. The target organs are mainly
      lung, bladder, skin. Other relevant effects are skin lesions such as
      folliculitis. The studies on early biological effects (chromosomal aberrations,
      sister chromatid exchanges, micronuclei) have shown contradictory results, mainly
      because of differences in exposure intensity. The metabolic polymorphism may
      account for a higher susceptibility to lung and bladder cancer following exposure
      to risk factors; the role of PAH occupational exposure is however to be examined,
      and the use of indicators of genetic susceptibility is currently limited to
      research programs. Health surveillance for PAH exposed workers is funded on the
      Italian laws (DPR 303/56 and D.Lgs. 626/94) and it is mainly dedicated to
      prevention of carcinogenic effects. Preventive examinations should consider PAH
      target organs (skin, lung, bladder, larynx) and look for early signs and
      symptoms. Particular attention will be paid to life habits such as tobacco
      smoking or diseases which could represent condition of susceptibility. Periodical
      examinations (every six months) will similarly evaluate PAH target organs. Health
      surveillance is also programmed for formerly exposed workers and the institution
      of exposure and cancer registries is mandatory. On the basis of the current
      scientific data, it is not advisable the use of tumor markers or cytogenetic
      tests at the individual level as well as the screening of asymptomatic PAH
      exposed workers for early diagnosis of lung or bladder cancer. Information and
      formation activities will be part of medical examinations and will be included in
      specific programs in cooperation with other company functions.

PMID- 9775008
TI  - [The toxicology and prevention of the risks of occupational exposure to aromatic
      polycyclic hydrocarbons. II. Toxicology. Exposure assessment. Environmental and
      biological monitoring].
AB  - The evaluation of exposure to polycyclic aromatic hydrocarbons (PAH) should
      firstly comply with current regulations (D.Lgs. 626/94), that is, identify the
      compounds and exposed subjects, quantify exposure, adopt preventive measures and
      health and epidemiological surveillance. Environmental monitoring should take
      into account the technological cycle and the tasks with higher PAH exposure risk,
      and the main sources of emissions. In the case of skin contamination, it should
      be considered the measure of skin PAH by means of sampling or removal techniques;
      moreover, the determination of urinary hydroxypyrene (1-HP) should be performed.
      It is mandatory to analyse (Benz[a]) anthracene; Benzo[b]fluroanthene;
      Benzo[j]fluoranthene; Benzo[k]fluoranthene; Benzo[a]pyrene;
      Dibenzo[a,h]anthracene, i.e. the PAH marked with the R45-R49 phrase. When 1-HP
      determination is planned, Pyrene should be added. Biological monitoring has been
      addressed mainly to hydroxylated metabolites of pyrene and among these 1-HP, the
      main metabolite of pyrene, although non occupational factors, such as tobacco
      smoking and consumption of smoked foods are potentially confounding. Urinary
      mutagenicity tests which are heavily influenced by non occupational factors such
      as tobacco smoking and diet are not advisable. The determination of DNA and
      protein adducts is a promising test for evaluation of metabolic active dose but
      at the moment it is not suitable for routine use in occupational medicine. In
      order to interpret environmental and biological data, it will be useful to
      consider appropriate reference values ("limit" "guide", "operative", "maximum
      admissible") such as 0.1 mg/m3 for total PAH extracted with benzene, 5
      micrograms/m3 for the mixture of 15 PAH listed by US NTP, the limits varying from
      0.1 to 5 micrograms/m3 for Benzo[a]pyrene, and 2.7-4.4 micrograms/g creat, for 1
      HP.

PMID- 9775010
TI  - [The use of neurophysiopathological technics in assessing pain syndromes in
      industrial medicine and rehabilitation].
AB  - The use of neurophysiopathological techniques in the assessment of pain syndromes
      in occupational and rehabilitative medicine. Pain is one the major causes of
      disability. In occupational medicine this is translated into a loss of working
      days or the need to change jobs. In rehabilitation pain limits treatment and
      often lengthens recovery time. Neurophysiopathological techniques can be used to
      improve neuroalgological diagnosis and gain better understanding of pathogenic
      mechanisms thus allowing therapy to be targeted more precisely aiding the
      subject's social and occupational recovery.

PMID- 9775011
TI  - Work capacity of the upper limbs after mastectomy.
AB  - Cancer patients are now more often long-term survivors and their needs for
      returning to social and productive activities have become a primary focus of
      intervention. The purpose of the present study was to propose an objective
      evaluation test for predicting endurance capacity in breast cancer patients after
      surgery, in order to optimize return to work or previous daily activities, and
      for monitoring changes during rehabilitation. Twenty female patients (mean age:
      44 +/- 5), who underwent radical breast surgery 2 months before being referred to
      our Unit, participated in the study. In addition to the measures of the
      circumferences in the arm-forearm and manual muscle strength test, we performed
      the following functional evaluations: 0-100 Constant scale for shoulder function;
      instrumental evaluation of daily/occupational upper limb activities (Lido
      WorkSET). We monitored the mechanical parameters, the perception of effort, pain
      or discomfort, and the range of movement while performing a 3-minute steady
      daily/occupational task chosen by the subject. Patients were asked to perform the
      3-minute test at three different intensities ("moderate", "somewhat hard",
      "hard") until the perception of fatigue, pain or discomfort was rated > 3 on the
      10 point Borg's scale. The 'power-duration' product (Watt x min) defined by the
      three tests (see Fig. 1) represented the individual tolerable work load, since
      subjective indicators of pain/discomfort remained within tolerable limits during
      the exertion. On this basis, patients were encouraged to return to levels of
      daily physical activities compatible with the individual tolerable work load. The
      second evaluation, although no statistical analysis was performed, confirmed that
      the "guided" daily activity in a 2-month period increased patients' capacities
      and "trust" in their physical capacity.

PMID- 9775012
TI  - Effects of ethanol on toluene metabolism in man.
AB  - The aim of this paper was to study the possible causes for metabolism changes due
      to ethanol and solvents interactions. In literature the effects of interaction
      between some solvents (toluene, xilene, TCE, etc.) and ethanol in acute
      experimental exposure are well known: the ingestion of a moderate amount of
      ethanol (0.8 gr/Kg) before inhalatory exposure to solvents causes the hematic
      levels of the solvent itself to increase and the urinary excretion of the main
      metabolites to decrease. In our study we have analyzed the possible effects of
      exposure to toluene vapours on elimination of toluene itself in urine, which is a
      useful biological index of occupational exposure to toluene. 5 healthy volunteers
      were exposed to toluene vapours (100 mg/m3 for 4 hours) with and without
      simultaneous ethanol consumption (0.5 g ethanol/Kg body weight) in an exposure
      chamber. The ethanol was ingested two minutes before entering the chamber and two
      hours after beginning of exposure in order to reach ethanol and toluene maximal
      concentrations in blood simultaneously. The blood and urine were collected at the
      beginning and at the end of exposure in order to measure toluene and ethanol. The
      analyses were performed by means of a Gas Chromatograph (GC) Hewlett-Packard 5880
      A connected with a Mass Selective Detector (MSD). The obtained results show that
      ethanol causes a decrease in toluene metabolism: in fact, with constant
      environmental exposure, toluene concentration at the end of exposure increases in
      blood from 156 micrograms/L to 285 micrograms/L (+84%) in presence of ethanol;
      the same happens to the amount of toluene eliminated in urine (+45% in presence
      of ethanol), while the metabolized amount of toluene (hippuric acid in urine) was
      lower in presence of ethanol (1492 mg/g creatinine in comparison with 2251 mg/g
      creatinine; 37%). These results show that a moderate amount of ethanol changes
      toluene metabolism: this phenomenon may be an important source of error in the
      biological monitoring of solvent exposure.

PMID- 9775013
TI  - [An anamnestic-observational estimation of the postural-energy-motor commitment
      of occupational activities via a questionnaire].
AB  - A simple questionnaire for the quali-quantitative clinical assessment of the
      physical requirements in habitual occupational activities has been fixed. The
      assessment goes through the classification of qualitative, dimensional, temporal
      parameters referred by the patient as characteristic of the occupational
      activity. As a result the risk factors related to postures and movements are
      highlighted, and an esteem of the energy expenditure is obtained from a
      predictive equation which has been formulated on the basis of some important
      references. The energy expenditure of three homogeneous occupational phases was
      estimated through the equation, and then measured during a simulation of the same
      activities performed in a laboratory by 7 subjects. The estimated and the
      measured values were compared also with the esteems obtained from validated
      predictive equations (Garg et al, 1978). The predictivity of our equation was
      measured. As an on-site assessment, detailed written reports of 18 occupational
      phases were submitted to 6 differently trained observers and were analyzed
      through the questionnaire; the variability inter-observer was studied.

PMID- 9775014
TI  - [Collaboration between physicians and economists for a more advanced health
      management].

PMID- 9775015
TI  - [The organization of the health enterprise].

PMID- 9775016
TI  - [A proposed methodology for an attempt at evaluating the research activities
      included in a hospital structure].

PMID- 9775017
TI  - [Treatment of acromio-clavicular dislocations using coracoacromial ligament
      plasty].
AB  - PURPOSE: Plasty transfer using the coracoacromial ligament (Cadenat) for the
      treatment of acromioclavicular separation is usually too weak and too short. The
      authors used a reinforcement flap, made by a lateral supraclavicular detachment
      of the superior fibrous-capsular sheath. MATERIAL AND METHOD: Twenty-six
      acromioclavicular separations were radiographically studied using an axillary
      view. Twenty-one patients had a posterior dislocation of the lateral end of the
      clavicle. A pouch formed by the superior detachment was present in all cases with
      posterior displacement. In 19 case out of 26, this detachment was used to create
      a quadrangular flap with acromial support. The end of the coracoacromial ligament
      was attached to this long flap which provided adequate reinforcement along its
      entire length. RESULTS: There was a statistical correlation (p = 0.05) between
      the posterior component of the separation and the presence of this detachment. In
      the 19 reinforced plasties, no recurrence of posterior dislocation was reported,
      a mild undercorrection and 2 overcorrections were noted. Recurrent posterior
      dislocation was reported in the 7 non-reinforced coracoacromial plasties, and
      superior dislocation was reported twice. DISCUSSION: Posterior acromioclavicular
      dislocation is present in 80 per cent of cases. Diagnosis mainly uses the
      axillary view. It is always associated with a lateral supraclavicular detachment
      providing a 3 to 5 cm long downward flap which is used as a natural reinforcement
      for the coracoacromial ligamentoplasty.

PMID- 9775018
TI  - [Static and dynamic changes of the cervical spine after laminectomy for cervical
      spondylotic myelopathy].
AB  - PURPOSE OF THE STUDY: Extensive cervical laminectomy has been widely used in the
      treatment of progressive myelopathies secondary to stenotic conditions.
      Complications of this procedure such as spinal instability, accelerated
      spondylotic changes, postoperative spinal deformity and constriction of the dura
      mater by extradural scar tissue formation have been recognized. However, the
      frequency of these complications is probably overestimated and their consequences
      on the clinical outcome remain unknown. The purpose of this report was 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
      films in the prevention of postoperative destabilization. MATERIALS AND METHODS:
      30 patients older than 30 years who underwent a laminectomy of more than 3 levels
      without fusion for myelopathy secondary to cervical spondylosis were reviewed
      retrospectively with an average follow-up of 5 years. Functional results were
      evaluated according to the Japanese Orthopaedic Association 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 one in order to identify the changes in the curvature of the cervical
      column, in the range of motion of the neck, in the intervertebral angular
      mobility and antero-posterior displacement of the vertebral bodies, and finally
      to identify the incidence of spinal instability. RESULTS: 18 patients (31 per
      cent) developed postoperative changes in cervical spine curvature. 15 patients
      (25 per cent) had one or more destabilized levels. Deformities of the cervical
      spine occurring after surgery do not appear to cause any symptom or neurologic
      abnormalities. Destabilization required repeat surgery in 3 patients. All the
      levels found destabilized on the postoperative films were hypermobile on the
      preoperative dynamic radiographs. A preoperative olisthesis without hypermobility
      was not a risk factor for postoperative destabilization. CONCLUSION: The use of
      preoperative dynamic radiographs should improve the selection of patients
      undergoing laminectomy for the treatment of multilevel cervical cord compression.
      Dynamic X-rays may also reinforce the need for possible adjunctive procedures
      such as fusion and instrumentation, in order to prevent a postoperative
      destabilization. A preoperative olisthesis with a hypermobility in sagittal or
      horizontal planes must be fused and instrumented.

PMID- 9775019
TI  - [Traumatic lesions of the deep branch of the radial nerve].
AB  - PURPOSE OF THE STUDY: We report a retrospective study of 21 patients treated for
      an injury of the deep branch of the radial nerve. The aim of this study was to
      precise the indication and to evaluate the results of nerve surgery and tendon
      transfer. MATERIAL: 21 patients, mean age 32, with complete divided lesion of the
      nerve due to open injury were included. 5 cases with fresh discision of the deep
      branch of the radial nerve were treated in emergency by suture repair. 16 cases
      were old lesions. 6 of them had initially severe associated lesions involving
      skin, forearm muscles or radius. In this case, the treatment of the nerve lesion
      was delayed after the treatment of the associated lesions. 10 were simple lesions
      of the nerve who were initially misknowned (6 cases) or caused by a surgical
      procedure at the proximal forearm (4 cases). METHODS: 4 patients had tendon
      transfers, due to a very old lesion for one of them and a severe muscle
      involvement for the 3 others. Twelve nerve graft repairs were performed. Their
      were 8 troncular grafts and 4 fascicular grafts because the lesion was in the
      posterior forearm at the level of the terminating branches of the nerve. They
      required a mean length of 5.8 cm and an average of 3 to 4 cables for nerve graft.
      RESULTS: The mean follow up was 25 months. Results were appreciated on the
      recovery of 5 functions (supination, fingers extension, thumb abduction, thumb
      retropulsion, wrist postero-ulnar extension). Primitive nerve repairs had full
      recovery in all cases. Tendon transfers had good results. The 12 nerve grafts had
      2 excellent results, 8 good results, 1 fair and 1 poor result. These 2 last cases
      required secondary tendon transfers. DISCUSSION: Traumatic lesions of the deep
      branch of the radial nerve are often misknowned and often iatrogenic. Nerve
      surgery provides better functional results than tendon transfers. Nerve grafts in
      delayed nerve repairs are possible even if the lesion is distal. They give
      excellent or good functional recovery in most cases after a delay of 7 months.
      Tendon transfers are indicated if nerve surgery fails or in case of large forearm
      muscle defect, old patient, and when the delay after the injury is superior to 12
      months.

PMID- 9775020
TI  - [Use of a Russel-Taylor nail for stabilizing fractures of the femur. Apropos of
      57 fractures with 30 computed tomographies of the rotation].
AB  - PURPOSE OF THE STUDY: A clinical and radiographical study with CT in 30 cases was
      undertaken in femoral fractures fixed with Russel-Taylor intramedullary nail.
      MATERIAL AND METHODS: In this retrospective study of 57 femoral fractures (mean
      follow-up 22 months), all fractures were analysed according to the classification
      of Wiss and Winquist-Hansen-Clawson. Fixation was performed with Russel-Taylor
      intramedullary mailing. Fifty fractures were classified as unstable due to the
      type of fracture and for its localization. Analysis of the clinical and
      radiographical results was performed immediately postoperatively and later by CT
      (30 cases). RESULTS: Clinical results showed seven cases of hip pain and limited
      walking capability; twenty with decreased hip mobility; twenty-one with
      functional impairment of the knee with limited flexion (11 cases) and/or knee
      sprain (15 cases). Radiographical results showed sixteen cases of leg shortening
      inferior to 1 cm, three between 1 and 2 cm, and one exceeded 2 cm; nine with
      varus angulation of 5 degrees, one with valgus angulation of 5 degrees, and seven
      with external rotation exceeding 10 degrees, five with internal rotation
      exceeding 10 degrees. Results were determined according to Thorensen's criteria.
      DISCUSSION: The use of Russel-Taylor intramedullary nail for the management of
      complex femoral fractures is discussed. Rotational deformities appeared related
      to the quality of reduction during surgery. Because of the stiffness of this type
      of nail, a smaller diameter can be used. Result analysis demonstrates that static
      nailing should probably be used more frequently in unstable femoral fractures.

PMID- 9775021
TI  - [Incidence of arthrosis in the results of the treatment of coxarthrosis in the
      young adult with Chiari's osteotomy. Retrospective study of 52 hips with 10.5
      years of follow-up].
AB  - PURPOSE OF THE STUDY: Fifty two of 53 Chiari pelvic osteotomies performed between
      1974 and 1991 were reviewed clinically and radiographically with an average
      follow-up of 10.5 years. MATERIAL AND METHODS: In more than 46 per cent of cases,
      the osteotomy was performed on a dysplastic painful hip with severe
      osteoarthritis. Major complications were rare. The Chiari's osteotomy fixation
      screw was removed in 16 cases. Technically, the average displacement was 22 mm. A
      ascending osteotomy, related to the level of the osteotomy (p = 0.001), provided
      good displacement. RESULTS: The functional results were very good or good in 65
      per cent of the patients and lasted more than 10 years. Seventy five per cent of
      the hips were pain free. Radiographically, the center edge angle and the femoral
      head covering were corrected by the procedure. Degenerative changes of the hip
      joint were improved or stabilized in 63.5 per cent of the cases. Fifteen hips had
      undergone secondary total hip replacement, seven during the first five years and
      8 after 13 years. DISCUSSION: Factors associated with a positive outcome
      included: age under 30 at the time of surgery (80 per cent of survivorship up to
      15 years of follow up), low stage (I or II) of osteoarthritis, and a technically
      perfect Chiari osteotomy. The outcome of initial stage III or IV initial
      osteoarthritis were not as long lasting. Chiari osteotomy functional results were
      good for the initial 10 years, after this time they deteriorated quickly.
      CONCLUSION: Chiari pelvic osteotomy is an alternative procedure to early total
      hip replacement for severe painful dysplastic hips with low stage of
      osteoarthritis in young patients.

PMID- 9775022
TI  - [Treatment of aseptic acetabular loosening by reconstruction combining bone graft
      and Muller ring. Actuarial analysis over 11 years].
AB  - INTRODUCTION: One reason for the limited longevity of total hip replacement is
      the progressive bone loss resulting from iterative loosenings of acetabular
      components. In the early 80's was developed an experience at our institution for
      revision surgery of aseptically failed cemented acetabular components using a
      Muller ring. At that time, this device was used in combination with structural
      grafts. This appeared to us to be the safest method to address severe acetabular
      destructions. We are now able to report long term results. MATERIAL AND METHODS:
      We carried out a retrospective study on 81 cemented acetabular revision
      arthroplasties performed at our institution between 1981 and 1991. In all cases,
      there was a segmental or an important cavitary roof defect. Reconstruction of the
      acetabulum was performed using a superior structural bone graft combined with a
      Muller ring. Results are given with a mean follow up of 8 years (5-14 years),
      except in the survivor analysis, in which all patients were included. RESULTS:
      There was 15 iterative aseptic loosenings of the acetabular component (in which 5
      repeated revisions). Using iterative aseptic loosening of the acetabular
      component revised or not as an end point, the 10 year cumulative survival rate
      (CSR) was 0.72 +/- 0.14 and the 11 year CSR was 0.55 +/- 0.24. The position of
      the hip biomechanical center, the polyethylene thickness, or the type of the
      superior defect (segmental or cavitary) were not found to influence significantly
      roentgenographic results. DISCUSSION: Reconstruction of severely destroyed
      acetabuli using this method gave satisfactory results within the first decade.
      However, the hip function could not be reliably maintained over 10 years.
      Mechanical failures were related to resorption of weight bearing structural bone
      grafts. Aseptic iterative loosenings are often moderately symptomatic and yearly
      roentgenographic controls are necessary to detect late migrations. The lack of
      long term follow up may result in major bone loss, which can impair the
      conditions of iterative acetabular reconstructions.

PMID- 9775023
TI  - [Importance of arthrodesis of the big toe combined with a metatarsal alignment
      according to Lelievre in the surgery of the rheumatoid forefoot. Apropos of 70
      observations].
AB  - PURPOSE OF THE STUDY: The authors reviewed 70 cases of rheumatoid forefoot
      treated by Lelievre, lateral metatarsal resection alignment, associated to first
      metatarsophalangeal joint arthrodesis. MATERIAL: Rheumatoid arthritis evolution
      was 20 years an average. It involved cortico-dependent polyarthritis in 48 per
      cent cases. Metatarsalgia were always present. METHODS: Mean follow up was 44
      months (minimum 24 months) Results were analyzed according to Gainor. RESULTS:
      Foot pain disappeared in thirty two cases. Shoe wearing was normal 50 times.
      Arthrodesis fused 55 times. Lateral toes metatarsophalangeal joint space was
      satisfactory 28 times. Metatarsal divergence improved, 80 per cent of patients
      were satisfied in a subjective estimation and 85 per cent using Gainor's
      criteria. DISCUSSION: First-Metatarsophalangeal joint arthrodesis ensures
      permanent stability of the first ray and therefore an harmonious support
      distribution. The dorsal surgical approach allows an early weight bearing in
      cortico or immuno dependent patients. CONCLUSION: This technique keeps a low
      morbidity and ensures stable mid term results.

PMID- 9775024
TI  - [Anterior snapping of the hip associated with the ilial psoas].
AB  - Anterior snapping of the hip was first described in 1951 by Nunziata and
      Blumenfeld. The aim of this study, based upon a personal series and backed up by
      literature reports, is a current review of this common clinical condition,
      usually asymptomatic, but sometimes painful especially in athletes. MATERIAL AND
      METHOD: 12 cases in 11 patients were treated surgically: 4 men and 7 women, mean
      age 25 years, 7 of them regularly involved in sport. The onset of the snapping
      was sudden in 6 cases, related to a precise movement, while in 6 cases pain
      preceded the gradual development of snapping. Pain may coincide with snapping, or
      may be of a "chronic" nature after exercise. The problem had been present for 2
      years on average before treatment. Surgery consisted of posterior psoas
      aponeurotic fascia division and was sufficient in 11 cases. In one patient,
      disappearance of snapping was obtained only after division of the ilio-femoral
      ligaments. Mean postoperative follow-up was 6.5 years (1 to 12 years). Pain
      disappeared in all patients. A slight, intermittent and asymptomatic snapping
      persisted in 3 cases. All athletes regained their previous performance level.
      DISCUSSION: CLINICAL: Symptoms consist of a dull, deep clicking sensation in the
      groin during active mobilization of the hip. It never occurs with passive
      mobilization. The entire problem is that of attributing painful symptomatology to
      snapping. ANATOMICAL STUDY: In almost all cases, snapping is due to a sudden
      movement of the psoas aponeurotic fascia on the ilio-pectinate eminence. Other
      causes have been reported: ilio-femoral ligaments on the femoral head, rectus
      femoris or psoas tendon on bony crests or of psoas on the cotyloid cup of an
      artificial hip. INVESTIGATIONS: These are primarily designed to rule out any
      other cause of snapping or inguinal pain (foreign body, acetabular labrum lesion,
      etc). Bursography and dynamic ultrasonography identify the snapping site, but it
      is sometimes difficult to confirm that this is responsible for painful symptoms.
      TREATMENT: If such responsibility is confirmed, and if any psychological
      component can be ruled out, this should first be "medical" by stretching and
      local injections in the serous bursa. Surgery should consist in division of the
      psoas aponeurotic fascia, leaving the muscle fibers intact. The procedure should
      be performed under sensory epidural anesthetic, the only way of ensuring
      peroperatively that snapping has disappeared. Division of the psoas distal tendon
      at the lesser trochanter is not appropriate.

PMID- 9775025
TI  - [Simultaneous traumatic dislocations of the index finger. Apropos of a case with
      review of the literature].
AB  - A new case of simultaneous dislocation of the proximal and distal interphalangeal
      joints on the same digit is reported. This injury is uncommon in the index. The
      forces were applied to the finger tip in hyperextension position. Closed
      treatment provided a good result with full range of motion. Therapeutic options
      are discussed.

PMID- 9775026
TI  - [Non-traumatic circumscribed myositis ossificans. Apropos of a bilateral
      localization].
AB  - The authors report one case of a bilateral atraumatic circumscribed myositis
      ossificans (C.M.O.) developed from the triceps muscles with major equinism, in a
      15 years old girl. One side presented a current tumor, the other was seen at the
      first episode. The authors obtained a good functional result after surgical
      treatment and advocate this treatment.

PMID- 9775027
TI  - [Chronic instability of the proximal tibio-fibular articulation: hemi-long biceps
      ligamentoplasty by the Weinert and Giachino technique. Apropos of 3 cases].
AB  - PURPOSE OF THE STUDY: Recurrent dislocations of the superior tibiofibular joint
      are rare. We report three cases of Weinert and Giachino ligament reconstruction.
      MATERIALS: From 1989 to 1994, two soccer players and one young girl (10 years
      old) presented recurrent dislocation of the superior TFJ. The mechanism was a
      direct trauma, and the type of dislocation was antero-lateral. These patients
      were free of tibial fracture, major ligament lesion of the knee, and neurologic
      symptoms (peroneal nerve injury). Pain was over the fibular head, mechanical and
      increased by jumping. A lateral "cracking" was present. Examination showed an
      antero-posterior mobility of the fibular head. X-ray showed horizontal proximal
      tibiofibular joint. M.R.I. eliminated a lateral meniscal pathology and collateral
      ligament injury. METHODS: The biceps tendon was split longitudinally for
      approximately seven centimeters. The posterior one half was transected proximally
      and mobilized. Secondly, the free end of the graft was passed posterior to
      anterior through a tibial tunnel. Thirdly, the tendon was sutured to the anterior
      tibial periosteum under tension with the fibular head reduced. RESULTS: Follow up
      at one year revealed that all the patients were active, free of dysfunction and
      laxity, with no further episodes of instability and no loss of ankle mobility.
      DISCUSSION: The diversity of treatments reported for this rare dislocation led us
      to believe that none proved its superiority. Resection of the proximal end of the
      fibula involves extensive dissection and creates a risk for the peroneal nerve
      vacuum and a lateral laxity. Arthrodesis of the superior tibiofibular joint
      without fibular osteotomy leads ankle pain, instability and a loss of ankle
      mobility. This procedure may also be complicated by screw loosening or breakage
      or by stress fracture of the fibula at the screw site. Arthrodesis of the
      superior tibiofibular joint with fibular osteotomy avoids these risks, but is
      possible for pain in the diaphyseal resection during the first 6 post operative
      months. Weinert and Giachino procedure, using a portion of the biceps tendon to
      reconstruct the superior tibiofibular ligament successfully stabilizes the
      superior tibiofibular joint, preserves all physiological function of the fibula
      and avoids resection or arthrodesis complications. CONCLUSION: Based on our
      experience with these three patients and on literature review, ligament
      reconstruction for recurrent dislocation of the superior tibiofibular joint gives
      stability and indolence, and avoids complications of resection and arthrodesis.

PMID- 9775028
TI  - [Rapid chondrolysis after arthroscopic external meniscectomy. Apropos of 4
      cases].
AB  - The authors report 4 cases of rapid lateral femoro-tibial chondrolysis following
      arthroscopic lateral meniscectomy. All patients were young athletes. At the time
      of meniscectomy, the cartilage of the lateral compartment was normal. Only one
      meniscectomy was done with the Ho Yag laser. Clinical symptoms were always
      identical: pain and important swelling, persisting despite intra articular
      injections of corticosteroids. A second-look arthroscopy was performed after a
      mean delay of 6 months (5 to 8), showing numerous cartilaginous debris floating
      in the joint (like in a chondromatosis disease) and a severe cartilaginous damage
      in the lateral compartment (grade 3 or 4). Swelling disappeared after
      arthroscopic lavage followed in two cases by a non weight bearing period of one
      to two months. But X-rays always demonstrated a narrowing of the lateral joint
      line on flexion-full weight bearing AP views. Rapid chondrolysis is a rare and
      severe complication of lateral meniscectomy. The etiology, which is mechanical,
      is not known. It probably represents an acute form of chronic, slow chondrolysis
      which is frequent after lateral meniscectomy. Rapid chondrolysis should be
      treated urgently by the following protocol: arthroscopic lavage, intra articular
      injections of corticosteroids and non weight bearing period.

PMID- 9775029
TI  - [Importance of MRI in the diagnosis of meniscal ossicle. Apropos of 2 cases].
AB  - PURPOSE OF THE STUDY: To determine the contribution of magnetic resonance (MR)
      imaging in the diagnosis of meniscal ossicle. MATERIALS AND METHODS: Two cases of
      meniscal ossicle were evaluated by plain radiography and MR imaging. Sagittal and
      coronal T1-weighted (400/15), proton density and T2-weighted (2,000/20,80)
      sequences were performed with 0.5 T magnet. RESULTS: Plain radiography revealed a
      triangular ossified body in the postero-medial aspect of the knee joint. MR
      images demonstrated that these ossicles were located within the posterior horn of
      the medial meniscus. The signal of these ossicles was isointense with that of
      bone marrow in all sequences. CONCLUSION: MR findings allow the diagnosis of
      meniscal ossicle and help to differentiate it from osteochondral loose body.

PMID- 9775030
TI  - [Surgical treatment of myeloma localized in the spine].
AB  - PURPOSE OF THE STUDY: Myeloma represents as much as 40 per cent of malignant
      primary spine tumors. The aim of this study was to discuss the indications for
      surgical treatment of spinal myeloma. MATERIAL AND METHODS: 18 patients
      presenting spinal localization of myeloma were operated on. There were 10 males
      and 8 females. Mean age was 59.9 (41-86). Pain was present in all patients. Seven
      patients presented neurologic signs: Frankel B: 1 case, Frankel C: 3 cases,
      Frankel D: 3 cases. Surgical treatment included anterior approach in 6 cases,
      posterior approach in 5 cases and combined approach in 7 cases. Postoperative
      medical treatment (chemotherapy, radiotherapy, immunotherapy) was performed in
      all cases. RESULTS: Diagnosis was made after surgery in 10 patients on
      histological findings. There were 13 myelomas and 5 plasmacytomas. Decrease of
      pain was observed in all cases at first postoperative month; 9 patients were pain
      free at the 6th postoperative month. Complications occurred in 4 cases: 2 local
      infections after radiotherapy; mobilisation of an anterior implant in one case
      and local recurrence in one case requiring secondary surgery. Nine patients were
      alive at review with a mean follow-up of 57 months. Nine patients were dead with
      a mean follow-up of 15.4 months. Preoperative Karnofsky score was 50 per cent;
      Karnofsky score was 77 per cent at follow-up. Neurologic deficit improved in 5
      out of 7 cases. DISCUSSION: Primary treatment of myeloma is medical associating
      chemotherapy, corticotherapy, radiotherapy and immunotherapy. Plasmocytoma is
      frequently revealed by neurologic deficit. Staging of myeloma gives the
      prognostic. Surgical treatment must be performed when pain is not controlled by
      medical treatment or when neurologic deficit is present. CONCLUSION: Surgery
      allows rapid and durable functional recovery in patients with spinal myeloma;
      surgery should be associated to additional medical treatment, unlike spinal
      metastasis.

PMID- 9775031
TI  - [Intravenous iron in the treatment of postoperative anemia in surgery of the
      spine in infants and adolescents].
AB  - PURPOSE OF THE STUDY: Spinal fusion surgery often leeds to massive bleeding
      responsible for anemia in the postoperative period. The aim of this study was to
      compare the effect of IV iron III hydroxide sucrose complex (Venofer) versus oral
      iron fumarate administration in postoperative anemia. The efficacy of both
      treatments was evaluated by comparing hemoglobin level in the postoperative
      period. METHODS: Two groups of sixteen patients, scheduled for anterior and/or
      posterior spinal fusion, were compared. Group 1, historical, was treated by
      supplementation of 10 mg/kg/day oral iron fumarate. Administration was started
      when hemoglobin level fell below 9 g/100 ml. Group 2 was treated by intravenous
      iron sucrose complex using same criteria as in group 1 for starting
      administration. The dosage of iron was individually adapted according to a target
      hemoglobin level of 13 g/100 ml and to the actual lowest hemoglobin level
      measured. The total iron deficit was calculated with the following formula: total
      iron deficit (mg) = 0.24 x body weight (kg) x (target Hb-actual Hb)(g/l). The
      patients were supplemented by 3 mg/kg/day until the calculated iron deficit was
      compensated. RESULTS: Both groups were identical regarding age and lowest
      hemoglobin level reached in the postoperative period. Hemoglobin increased by
      0.25 g/day in group 1, and by 0.36 g/day in group 2. In others words, the
      beneficial effect of IV iron versus oral iron administration was as high as 45
      per cent (p = 0.003). CONCLUSION: Intravenous iron therapy as ferric sucrose
      complex is a new and more effective form of iron therapy than oral iron therapy
      to restore postoperative hemoglobin after spinal surgery in children.

PMID- 9775032
TI  - [Repetitive release of the medial nerve in the carpal tunnel. Analysis of a
      series of 18 cases].
AB  - PURPOSE OF THE STUDY: This study analyzes 18 revision procedures for carpal
      tunnel release failure. MATERIAL: This series did not present any difference in
      terms of age compare to the population suffering from median nerve entrapment:
      mean age 56 years, 17 female and 1 male, 1 monolateral syndrome and 8 bilateral.
      Two third of the patients were seen between 2 and 9 months after initial surgical
      treatment. Most of the first surgical procedures were performed by an orthopedic
      surgeon (12/18). The approach was open (14/18) with 5 short incisions, and 4
      endoscopic releases. Clinical symptoms were worse or unchanged compare to prior
      to surgery. All the patients had EMG study and 15 had worse electric signs than
      before. Open surgical approach was always palmar using optic magnification for
      median nerve neurolysis. RESULTS: 16 times an incomplete section of the anterior
      retinaculum and 2 median nerve lacerations were found. All patients were seen
      with a follow up of more than 2 months. Results concerning pain and sensibility
      were good for 16 of them; regarding motor impairment, only 13 of them had a good
      result. Grasp was not improved for 50 per cent of them. Two patients had a result
      considered as bad (one NAD sequela and one median total laceration). DISCUSSION:
      In our series as well as in literature, failures of carpal tunnel release are due
      to incomplete section of the anterior retinaculum and sometimes to median nerve
      laceration. The second look has to be performed when there is no improvement or
      when the situation is worse after initial surgery. CONCLUSION: Incomplete section
      of the anterior retinaculum is the most frequent reason for carpal tunnel release
      failure. An EMG seems necessary to confirm diagnosis before revision surgical
      procedure.

PMID- 9775033
TI  - [Conditions for the consolidation of fractures of the femoral diaphysis after
      locked intramedullary flexible osteosynthesis].
AB  - PURPOSE OF THE STUDY: We present here the clinical results achieved with locked
      intramedullary flexible osteosynthesis (LIFO) system in femoral fractures. The
      two major advantages of the device are its flexibility an ease of use. MATERIAL
      AND METHODS: Over a period of 6 years, 42 patients were treated. Two died and 7
      were lost for follow-up, leaving 33 cases available for evaluation. Fourteen
      cases were specifically analysed for callus morphological characteristics:
      volume, length and width, and compared to 18 cases from a previous series
      involving 27 intramedullary unmatched appaired nailings. RESULTS: Results in the
      33 patients of this series are: no nonunion, 1 osteomyelitis in an open fracture,
      4 malunions (2 primary iatrogenic malunions, 2 secondary cases due to a weak
      fixation). Fractures united at a mean delay of 10 weeks, that is, 4 weeks less
      than with a nail. Morphological callus study also showed that the LIFO system
      generates about 25 per cent longer of peripheral new bone formation than a nail.
      CONCLUSION: A LIFO construct with 3 or even 4 pins yields a shorter healing time
      than a nail. Furthermore, it generates a callus of 25 per cent longer around the
      fracture. The four pins construct was found to be as dependable as a locked nail,
      and minimizes inventory. This technique is indicated in the treatment of all
      common femoral shaft fractures in adults.

PMID- 9775034
TI  - [10-year actuarial analysis of a cohort of 156 total hip prostheses of a cemented
      polished aluminum/polyethylene alloy].
AB  - PURPOSE OF THE STUDY: From 1983 to 1986, 156 alumina/polyethylene combination hip
      arthroplasties (131 patients) were performed at the Henri Mondor Hospital. Before
      1983, the stainless-steel/polyethylene combination was performed. In this follow
      up study, the outcome of the first 156 consecutive alumine-polyethylene
      combination hip arthroplasties were analyzed with clinical and radiological
      features. The comparison of the two combinations was analyzed. A survival
      analysis was performed over a ten years interval. MATERIAL AND METHODS: The
      femoral component of the prosthesis was made of Titanium alloy (TiA16V4). The
      femoral head was made of dense alumina (A1203). The head diameter was 32 mm. The
      socket was made of ultra-high-molecular-weight polyethylene (UHMWPE). Fixation of
      head to stem was obtained through conical sleeving. We used a posterolateral
      approach, and a cemented THA without pressurization. At last follow-up
      evaluation, 90 patients were reviewed, 9 patients were interviewed by phone.
      Three patients were dead and 20 patients were lost for follow-up evaluation, in
      the first year. Nine failures were reoperated. The major cause of failure was
      septic complication of the THA (8). The average age of patients at arthroplasty
      was 58.1 year. The clinical evaluation was performed with the Merle d'Aubigne,
      Postel scoring system. The radiographs of 117 hips out of the 156 were available
      for this evaluation. Radiolucents, failures and wear were analyzed. RESULTS:
      There was a 5 per cent rate (8 hips) of deep infection due for two hips to the
      underlying pathology. Ten (6.5 per cent) of the 156 hips had had an episode of
      dislocation at last follow-up. Eighty-nine per cent of the hips were rated
      excellent, very good, and good; 9.3 per cent were rated fair: and 1.7 per cent
      were rated poor. The radiographs of the socket revealed 54 per cent of bone
      cement radiolucent and three failures at last follow-up. The radiographs of the
      stem revealed 29 per cent of bone-cement radiolucent and one failure at last
      follow-up. There was no revision of the femoral stem. Survival analysis (aseptic
      failures) depicted 93.45 per cent durability of the arthroplasty at 10 years. The
      survival analysis for the socket alone, using the same criteria for failure,
      demonstrated 94.53 per cent survival success at 10 years, and 98.91 per cent for
      the stem component. The comparison of the two combinations gave us a survival
      analysis for the socket alone, using aseptic failure as criteria, 79.84 per cent
      for stainless-steel/polyethylene combination at 8 years, and 97.63 per cent for
      alumina/polyethylene at the same time. CONCLUSION: The alumina/polyethylene
      combination with a 32 mm head diameter gave better results than the stainless
      steel/polyethylene combinations. The improvement was noted on the acetabular
      component.

PMID- 9775035
TI  - [Effect of arthroscopic fluid inflow on the femoro-patellar tracking. Comparative
      study of the dry and fluid filled knee].
AB  - INTRODUCTION: The dynamic study of the patello-femoral joint is of outstanding
      interest in unexplained anterior knee pain syndrome. Nevertheless, the accuracy
      of information regarding this particular point by means of video-arthroscopy is
      of concern, due to the surgical conditions of the procedure. The aim of this
      study was to appreciate the effect of serum inflow on the visual evaluation of
      the patello-femoral tracking during conventional knee arthroscopy. MATERIAL AND
      METHODS: The study group included 100 knees in 68 male and 32 female patients.
      Mean age at surgery was 36 years (range, 13 to 69 years). Indication for knee
      arthroscopy was: meniscal and/or ligament injury in 77 knees (group I), patello
      femoral pain in 13 knees (group II), tibial tuberosity screw removal in 7 knees
      (group III) and "mysterious" painful knee in 3 patients (group IV). Arthroscopic
      technique was conventional; general anaesthesia, pneumatic tourniquet, single
      antero-lateral portal and serum inflow by simple gravity. We measured the minimum
      flexion angle that was necessary to obtain de visu a perfect centralization of
      the patella dome into the trochlear groove in two situations: before inflating
      the knee ("dry" angle) and after serum inflow ("serum" angle). RESULTS: The
      average value of the flexion angle providing perfect centralization (FAC) in the
      "dry" situation and in the "serum" situation was 31 degrees (range, 10 to 75
      degrees) and 38 degrees (range, 20 to 85 degrees), respectively. Of the 100
      studied knees, the average difference between the "serum" and the "dry" FAC was
      about 7 degrees (6 degrees 45', standard deviation: 3 degrees 56') and was
      superior to 10 degrees in only one occasion; this difference is significative (T
      test; p < 0.0001). Conversely, there was no significant difference between the
      average differential FAC figure noted in each group of patients (ANOVA; p =
      0.28). DISCUSSION: The role, if any, of the tourniquet inflated around the
      proximal thigh is more or less constrictive, thus restricting the natural
      patellar tendency to shift laterally. Moreover, the absence of active quadriceps
      muscle contraction under general anaesthesia acts also in the same way.
      CONCLUSION: By comparison with the more natural "dry" situation, in nearly all
      occasions serum inflow by simple gravity induced less than 10 degrees of knee
      flexion overcourse until the obtention of a perfect patello-trochlear
      centralization. This data must be taken to consideration during arthroscopic
      examination of the patello-femoral tracking in the diagnosis of anterior knee
      pain that would remain unexplained after conventional imaging procedures.

PMID- 9775036
TI  - [Long-term survival rate of tibial osteotomies for valgus gonarthrosis].
AB  - PURPOSE OF THE STUDY: High tibial osteotomy (HTO) is a routine procedure for
      medial gonarthrosis. Mid-term results are known to be satisfactory, but they
      deteriorate with longer follow-up. The authors present a long term survival
      analysis of 109 out of 111 consecutive HTO with a minimal potential follow-up of
      ten years. MATERIAL AND METHODS: 111 patients were consecutively operated on for
      isolated primary varus gonarthrosis between 1977 and 1985: 57 men and 54 women,
      with a mean age of 53 years (range, 27 to 79 years). X-ray measurements were done
      on stance, hip-ankle view. Global axial deformation was defined as the angle
      between mechanical axes of femur and tibia. The respective part of congenital and
      degenerative tibial deformation was assessed according to Dejour. The angle
      between femoral and tibial bicondylar lines, representing lateral instability,
      was added to the tibial degenerative deformation to represent the total
      degenerative deformation. The goal of correction was a 3 to 7 degree mechanical
      valgus angulation. At the time of bone healing, 82 patients (74 per cent) had an
      optimal correction. Two patients were excluded from the follow-up study because
      of a severe complication (1 bacterial arthritis and 1 tibia non union) which
      could interfere with the long term result. The 109 remaining patients were
      followed for a minimal period of 1 year (mean: 8.4 years). GUEPAR pain grading
      and the occurrence of a revision were prospectively analyzed. 57 non reoperated
      patients could be re-examined at a mean maximal follow-up of 13.5 years (range,
      10 to 18 years). Failure was defined as either the occurrence of a grade 2 or 3.
      GUEPAR pain during the whole follow-up, or a clinical or functional Knee Society
      score < 80 points at final follow-up, or revision. Failure and revision rates
      were calculated according to Kaplan and Meier. RESULTS: 11 patients were
      reoperated on before final examination (10 per cent): 2 medial unicondylar and 9
      total knee prostheses. At final follow-up, the mean clinical and functional
      scores were respectively 87.0 points (range, 24 to 100 points) and 86.3 (range,
      45 to 100 points). The cumulative failure rate was 33 per cent after 10 years and
      54 per cent after 15 years; the respective revision rates were 9 per cent and 19
      per cent. A pre-operative total degenerative deformation superior to 3 degrees
      led to a 3.5 fold increased failure rate (p < 0.000,1). A pre-operative medial
      joint space narrowing over the half of the normal, lateral one led to a 2.2 fold
      increased failure rate (p = 0.014). An optimal post-operative correction led to a
      3.2 fold decreased failure rate (p = 0.000,1). For a given total degenerative
      deformation, patients with a congenital deformation superior to 5 degrees had a
      significant lower failure rate (p < 0.000,1). No factor significantly influenced
      the revision rate. DISCUSSION: Ideal patients for HTO, with an expected survival
      rate of 100 per cent after 13 years, have moderate degenerative changes and a
      congenital deformation superior to 5 degrees. Patients with advanced degenerative
      changes and no congenital deformation experienced a 35 per cent failure rate
      after 10 years. In this population, unicondylar replacement should be considered
      as a valuable alternative.

PMID- 9775038
TI  - [Osseous reconstruction of the patella with screwed autologous graft in the
      course of repeat prosthesis of the knee].
AB  - PURPOSE OF THE STUDY: The aim of this study was to propose an original way of
      solving the infrequent but difficult problem of a thin patellar remnant. After
      removal of the loose patellar button of a knee prosthesis, several options are
      available: patellectomy should be avoided because of unpredictable results;
      patelloplasty may be the solution if bone quality is too poor and can allow for
      its improvement with time; recementing a new implant needs the remaining patella
      to be thick enough (more than 10 millimeters). MATERIAL AND METHODS: We advised
      reconstruction with an autologous monocortical iliac bone graft, harvested from
      the medial cortex of the anterior iliac wing, and shaped to accommodate for the
      patellar remnant. Its cancellous surface is opposed to the roughened patellar
      bone to which it is fixed by four 1.5 mm cortical screws (the heads of which are
      countersunk). Any defect will be filled with cancellous chips. The patellar
      button can then be cemented. Two cases with a long follow-up (5 years) are shown:
      one is a "typical" indication of isolated patellar loosening 16 years after
      implantation of a GSB total knee prosthesis, in a 91 year old woman. The other
      one illustrates the salvage of a "patellectomized" multi-operated knee, in which
      a trochlear implant was used as a first step, then 4 years later the patellar
      pseudarthrosed remnant was reconstructed. DISCUSSION: Indications of this
      technique are obviously rare: the patellar remnant should be thinner than 10 mm,
      in one piece (or easy to rebuild with the graft), the bone should allow a good
      purchase of the screws and the extensor apparatus should be in continuity. The
      first cases seem encouraging, as no secondary fracture or non-union has been seen
      at five years follow-up. The bone-cement lucency seems to be due to cementing on
      a cortical surface, but did not increased. Autologous bone has been favoured to
      increase the chances of union in a poor quality bed. It has the drawback of a
      second approach to harvest the bone at the iliac wing, where it is not always
      flat. The surgeon must "cheat" to get as flat a surface as possible for
      cementing. The loss of quadriceps is so troublesome that Buechel has proposed
      autologous grafting inside the patellar tendon and Bakay has used a mushroom
      shaped allograft. Finally, we should like to advise against too much thinning of
      the patella to try and gain a few more degrees of flexion in total knee
      replacement: think of revision! CONCLUSION: We think this technique may be
      helpful in patellar loosening, as an other way of solving this problem.

PMID- 9775037
TI  - [Importance of intertibio-peroneal graft in pseudoarthrosis of the leg at risk
      for sepsis. Apropos of 21 cases].
AB  - PURPOSE: The purpose of our study was to analyze the use of intertibio-fibular
      bone grafting (I.T.F.G.) in non-union presenting a septic risk. MATERIAL AND
      METHODS: Twenty one non-unions of the tibial diaphysis presenting a septic risk
      were treated by intertibio-fibular bone grafting through a postero-lateral
      approach, over a seven year period (1988-1995). There were 2 septic non-unions
      and 19 non-unions following open fractures, all treated initially by external
      fixation. Seventeen patients were male, four were female. Mean age was 33 years
      (range 19 to 70 years). RESULTS: Healing was obtained in 20 cases, only one
      patient had a second bone grafting. Postoperative complications included two
      infections (one deep and one superficial) without consequences on bone healing.
      Functional results were good and excellent in 18 cases (85.7 per cent).
      DISCUSSION-CONCLUSION: Our study showed that among techniques for the treatment
      of non-union presenting a septic risk, the I.T.F.G. is one of the most reliable,
      with low morbidity and low cost. The authors recommend this type of surgery
      particularly in developing countries.

PMID- 9775039
TI  - [Scapulo-thoracic mycetoma. A rare localization, a particular form].
AB  - INTRODUCTION: An uncommon form and a rare localization of mycetoma is reported.
      The aim of this report was to distinguish this inhabitual form of mycetoma from
      some tropical diseases like onchocerca and other fungal diseases. CASE REPORT: A
      55 year old man was admitted 10 years after a septic worm-hole for a scapulo
      thoracic tumor. This encapsulated mass was a bending and rounded polyfistular one
      attached to the dorsal aspect of left shoulder. The fistula discharge a
      serosanguineous or purulent exudate. The characteristic red granule was not
      visible. The tumor was removed and histological examination was performed. A
      typical granuloma of red granule of streptomyces pelletieri was found. A good
      result was obtained with associated cotrimoxazole treatment. DISCUSSION: Scapulo
      thoracic form included: scapular, axillary and chest form of mycetoma. All these
      localizations are rare. One of them can be complicated by osteitis or pleuro
      pulmonary localization. Streptomyces pellitieri is the actinomycetic causal
      agent. This encapsulated form is uncommon. CONCLUSION: Scapulo-thoracic mycetoma
      is rare. Encapsulated and pedicular form is uncommon. Around Sahel areas,
      differential diagnosis must be evoked such as parasitic and mycobacterial
      infections.

PMID- 9775040
TI  - [Angulation deformity of a finger after local radiotherapy].
AB  - The authors report a case of a third finger angulation deformity. This radial
      deviation deformity is owed to a local radiation for verrucae vulgaris at 16
      years old. The treatment by corrective osteotomy of the phalange was performed
      with satisfactory correction and full restoration of function.

PMID- 9775041
TI  - [L5 sciatica caused by the compression of the lumbo-sacral trunk of osseous
      origin at the sacro-iliac level. Treatment by an antero-lateral subperitoneal
      approach].
AB  - A 42 years old patient presented with a 4 years history of a left L5 sciatica
      unresponsive to a previous L4-L5 surgical decompression. CT scan showed a solid
      tumor developed on the anterior aspect of the sacro-iliac joint, in contact with
      the lumbo-sacral trunk. An antero-lateral extraperitoneal approach was performed,
      with progressive subperitoneal dissection along the inner aspect of the iliac
      wing to the sacro-iliac joint and sacral ala. The exostosis was removed with "en
      block" excision, Postoperatively pain completely disappeared. Considerations are
      made on the mechanism of the compression as well as on the surgical approach
      performed.

PMID- 9775042
TI  - [Evolution of post-fracture bone deformities in an infant with hepatic
      osteodystrophy on Alagille syndrome].
AB  - INTRODUCTION: This case report describes the evolution of postfractural axial
      bone deviations that occurred in a child with hepatic osteodystrophy due to an
      Alagille Syndrome. Postfractural bone deformities in children trend to
      spontaneous correction if there is a remaining growth potential. In case of
      severe hepatic osteodystrophy correlated by liver transplantation, we have
      observed spontaneous correction of a posttraumatic valgus deformity of the leg,
      as well as worsening of a diaphyseal femoral bowing. We tried to explain this
      apparently paradoxal evolution. CASE REPORT: Andrea St. is born in 1984 with
      multiple malformations corresponding to Alagille Syndrome: ductulus paucity,
      pulmonary arterial hypoplasia, posterior embryotoxin and "butterfly vertebrae".
      She has developed a cholostatic icterial and a portal hypertension due to a
      hepatic cirrhosis which needed an hepatic transplantation at the age of 8 years.
      Before her transplantation, Andrea St developed postfractural axial bone
      deviations. At the age of 7 years, she had a tibia valgum of 20 degrees and a
      femoral bowing of 50 degrees. With the normalization of the metabolism due to the
      hepatic transplantation, the osteopenia as well the tibia valgum of 20 degrees
      has been corrected spontaneously up to 8 degrees and there was a worsening of the
      femoral bowing up to 50 degrees. DISCUSSION: The physiopathology of the hepatic
      osteodystrophy is not yet perfectly known. Treatment with Vitamin D and Calcium
      doesn't seem to prevent hepatic osteodystrophy. Salter reported that
      postfractural bone angulation in children will spontaneously correct itself if on
      one hand it is not far from the growth cartilage and on the other hand if it is
      in the same mobility plane than the adjacent articulation. Postfractural
      diaphyseal bone deformities tend to correct spontaneously if the angulation is
      less than 20 to 30 degrees. Concerning fractures of the proximal tibia in
      children, they develop frequently a progressive tibia valgum deformity, even if
      the fracture was not primary displaced. However we know that all proximal tibial
      fractures in children don't give residual valgus deformities, and that several
      postfractural tibia valgum correct spontaneously. This has been explained by a
      temporary growth acceleration of the medial part of the proximal tibial growth
      plate. In this case, the femoral bowing worsened. This is explained by the
      mediodiaphyseal location of the deformation, and the importance of the bone
      deviation much bigger than the threshold of 20 to 30 degrees that may not be
      overtaken to hope a spontaneous correction. The evolution of the proximal
      metaphyseal tibial fracture consisted firstly in a progressive valgus deformation
      that resolved spontaneously after hepatic transplantation.

PMID- 9775043
TI  - [Anatomo-clinical consequences of the vertical sectioning of the subscapular
      muscle in Latarjet intervention].
AB  - The goal of this study was to assess the effects of the vertical section of the
      subscapularis muscle (internal rotation and muscular degeneration) during
      Latarjet procedure. MATERIAL AND METHODS: From October 1st, 1990, to June 30th,
      1991, 40 patients were operated according to Latarjet for chronic anterior
      shoulder instability. A vertical section of the subscapular muscle was performed.
      Except for one female patient, all of them practiced sports. Preoperative delay
      between first dislocation and surgery averaged 59 months. Postoperative
      rehabilitation was aimed at external rotation, recovery began 48 hours after
      surgery, without specific indications as far as internal rotation was concerned.
      Sports activity was resumed 90 days after surgery. 38 were reviewed after 4
      years. Clinical review was made according to Constant's score and by measuring
      strength, and amplitude of internal rotation. Radiological assessment of the
      shoulders was made with standard x-rays and CT. RESULTS: For global results, we
      noted absence of recurrence, a weighted Constant score of 88 per cent, 87 per
      cent of patients satisfied or very satisfied, 55 per cent of the osteoplastic
      ridge were on level, 16 per cent were retracted, and 29 per cent overlapped, 19
      per cent non union or ridge lysis, 21 per cent glenohumeral osteophytosis. As far
      as clinical results are concerned, no significant difference was noted associated
      to osteoplastic ridge position. Internal rotation was assessed by measuring the
      distance hand to back (lift-off test). On the operated side it averaged 6 cm (0
      18 cm), on the other side 13 cm (2-21 cm). The difference between each side was
      statistically very significant (p = 0.0001). Strength in internal rotation on the
      operated side averaged 3 kg (0-8 kg), on the other side, 6 kg (2-10 kg). The
      difference between each side was statistically very significant (p < 0.0001). CT
      was carried out on thickness and degeneration of the subscapular muscle (n = 29).
      Thickness of the subscapular muscle (operated side) average 10.5 (5-17 mm) after
      surgery, and 14.6 mm before surgery. It was thimer than on the contralateral
      shoulder 21 mm (10-33 mm). In both cases (shoulder before and after surgery,
      operated and contralateral shoulder), the difference was statistically
      significant. Degeneration of the subscapular muscle showed 4 stage 0, 13 stage 1,
      5 stage 2, 6 stage 3, and 1 stage 4. A non statistical correlation was noted,
      between muscle degeneration and functional result, strength in internal rotation,
      distance hand to back. DISCUSSION: This series confirms efficiency and low
      morbidity of Latarjet procedure. Nevertheless, assessment of the subscapular
      muscle shows that 50 per cent of its strength and 50 per cent of its thickness
      were lost, 4 years after surgery. A significant degeneration (stages 2.3.4) was
      found in 41 per cent of the patients. This limitation is related to the trans
      subscapular approach and to the absence of internal rotation postoperative
      rehabilitation. CONCLUSION: A randomized study comparing the vertical trans
      subscapular approach to the horizontal trans-subscapular one would determine the
      better procedure.

PMID- 9775044
TI  - [Surgery of the spine in Duchenne's muscular dystrophy].
AB  - PURPOSE OF THE STUDY: The authors present a retrospective review of 27 patients
      presenting a Duchenne muscular dystrophy and who were operated for spinal
      deformity, with special reference to functional result and postoperative
      evolution of vital capacity. MATERIAL AND METHODS: Age at surgery averaged 14.
      Mean scoliotic angulation was 42 degrees. A thoraco-lumbar kyphosis was present
      in 15 cases (kyphotic index less than 10 degrees). A pelvic obliquity averaging
      17 degrees was associated in 19 cases. Mean pre-operative vital capacity was 56
      per cent. Preoperative evolution of vital capacity was documented in 18 cases:
      annual rate of decrease was 4.3 per cent. Heart ejection fraction averaged 63 per
      cent in 23 cases, and was normal in 4 cases. Instrumentation was extended from
      D3, D4 or D5 to L5 (5 cases) or S1 (22 cases). Spinal fixation was done in all
      patients by subliminar wiring with Luque rods (5 cases) or Hartshill rectangle
      (22 cases). Sacral fixation was done with ilio-sacral screws linked to the
      rectangle by Cotrel Dubousset rods and dominos (15 cases). RESULTS: Mean blood
      loss was 1750 cc. Postoperatively, 25 patients were extubated on the operative
      day, 1 patient at D + 1, and one patient underwent a tracheostomy after one
      month. Scoliosis was reduced to 10 degrees after surgery and 13 degrees after 30
      months follow-up. Pelvic obliquity was reduced to 4 degrees after surgery and 7
      degrees after 30 months. A good spinal balance was present after surgery in 20
      patients; at follow-up, a coronal or sagittal imbalance averaging 40 mm was
      observed in 22 patients. Postoperative evolution of vital capacity was documented
      in 21 cases. The annual decrease rate was 6.4 per cent. Rate was higher in
      patients presenting a good preoperative vital capacity (over 70 per cent) and
      very low in patients presenting a preoperative vital capacity under 40 per cent.
      10 patients were deceased at review after a mean 53 months survival, at a mean
      age of 19. 17 patients were alive with a 50 months follow-up. DISCUSSION: Spinal
      surgery in Duchenne muscular dystrophy has a low morbidity. It allows to keep
      sitting position to the child and to preserve quality of life. Surgery should be
      considered as soon as frontal or sagittal collapse of the spine is observed.
      However surgery does not result in respiratory improvement nor in life duration
      lengthening.

PMID- 9775045
TI  - [Treatment of scoliosis in the adolescent by anterior release and vertebral
      arthrodesis under thoracoscopy. Preliminary results].
AB  - PURPOSE OF THIS STUDY: The purpose was to evaluate short term results of
      thoracoscopic anterior release and fusion in adolescent scoliosis. MATERIAL AND
      METHODS: An independent observer reviewed retrospectively hospital files and X
      rays of 8 consecutive patients. The average follow-up was 14 months. The mean age
      at the time of surgery was 12 years old, all patients were skeletally immature.
      The surgical technique consisted in a thoracoscopic release and fusion of the
      discs space followed in the same time by a posterior instrumentation and fusion.
      Six cases were done in the prone position, two in the lateral decubitus. RESULTS:
      The release could be done in 7 cases. In one case a severe bronchospasm prevented
      from doing discectomy. Four levels in average could be released and fused. The
      thoracoscopic time was 240 mn in average and the total surgical time 430 mn. The
      bleeding of the thoracoscopic procedure was minimal (less than 200 cc) in all but
      one case (2000 cc). The duration of the chest tube was 4.4 days. At last follow
      up the cosmetic advantage was obvious. The angular correction of the Cobb angle
      was 63 per cent (similar to our isolated posterior instrumentation). The
      radiologic aspect of the anterior fusion seemed to be less satisfactory than the
      ones of classic thoracotomies (although we did not observe any non union).
      DISCUSSION: Our experience and these results moderate the initial enthusiasm of
      these new techniques reported in literature. Our current indications are
      therefore patients at risk of crankshaft, and complementary anterior fusion of
      dysplasic spines. As to the major curves we still recommend the anterior release
      through a formal thoracotomy which allows a more complete disc excision on more
      levels and a more abundant graft, with a shorter surgical time, with an
      associated morbidity which does not seem superior.

PMID- 9775046
TI  - [Giants schwannoma of the sacrum. Apropos of 3 cases and review of the
      literature].
AB  - Giant sacral schwannoma is a very rare tumor (25 cases reported). The authors
      report 3 cases of giant sacral schwannoma treated by curettage through posterior
      approach and discuss symptoms and treatment. These tumors were characterized by
      their minimal symptoms compared to radiographic findings. Magnetic resonance
      imaging must be performed in order to detect extraosseous tissue component and
      intradural invasion. A biopsy was performed to confirm the diagnosis before
      definitive treatment. Wide resection was proposed by many authors because of the
      high recurrence rate. We believe that a wide resection is too sever as it causes
      neurologic sacrifices. A curettage through posterior approach preserves nerve
      function, and if a local recurrence occurs it remains possible to perform a wide
      resection. When sacroiliac joint instability is detected, a lumboiliac
      arthrodesis is indicated. Osteosynthesis could be performed with spine device
      (using pedicular and iliac screws).

PMID- 9775047
TI  - [Fractures of the ischium after laminoarthrectomy. Retrospective study of a
      series of 31 patients].
AB  - PURPOSE OF THE STUDY: Pars interarticularis fracture is one possible source of
      pain after laminoarthrectomy. The purposes of this study were: to describe the
      pars defect, to determine its causes and to analyse its consequences on the
      functional final result. MATERIAL AND METHOD: 31 patients operated for disc
      herniation or degenerative lumbar stenosis were retrospectively studied. Clinical
      symptoms were evaluated before and 3 months after initial surgery, at the time of
      postlaminectomy radiological examination and at last follow-up according to
      Beaujon rating scale. Radiological evaluation included: description of the pars
      defect on plain radiographs and CT imaging, calculation of the amount of bone
      just above the inferior articular process that was resected, analysis of the
      postoperative stability of the spine both on static and dynamic radiographs. Any
      remaining disc herniation or stenosis were also noted. RESULTS: 39 pars
      interarticularis fractures were disclosed. These fractures were identified as a
      linear luency on plain radiographs or on reformed CT imaging view. Asymmetric
      widening of the facet joint space just below the pars defect was easier to
      observe and was present in 66 per cent of the cases on plain radiographs and in
      79 per cent on CT imaging. After initial surgery 12 slipping appeared. In all of
      these cases pars fracture was bilateral at the same level or associated to a
      complete unilateral facetectomy at the same level. The amount of bone resected
      just above the inferior facet process was 66 per cent in average, range from 45
      to 84 per cent. All the patients complained for low back pain and/or leg pain. In
      62 per cent of cases symptoms occurred within one year after surgery, at an
      average onset of 7.6 months postlaminectomy. 27 patients were reported Revision
      surgery was in all cases a posterolateral fusion with or without instrumentation;
      new decompression was performed in 15 cases. At last follow-up, according to our
      classification, results were very good in 9 cases, good in 15 cases and fair in
      the remaining 3 cases. Improvement rate obtained after the initial surgery was 75
      per cent in average, it was 59 per cent after revision surgery, difference was
      statistically significant. CONCLUSION: Pars interarticularis fractures may be a
      source of postlaminectomy pain. They appear to be caused primarily by an
      excessive resection (more than one half) of the bone immediately superior to the
      inferior articular process at the level of the laminectomy. These results suggest
      that caution in resection of this bone or additional posterolateral fusion in
      case of large resection of pars interarticularis, can avoid the problem.
      Asymmetric widening of the joint space just below the defect seems to be the key
      to this diagnosis in the postoperative lumbar laminectomy patient with persistent
      or recurrent pain.

PMID- 9775048
TI  - [Indentation fractures of the femoral head complicating the traumatic dislocation
      of the hip. Treatment by intertrochanteric osteotomy].
AB  - INTRODUCTION: Indentation fractures of the femoral head, are known to be rare
      with poor long-term prognosis. This study aimed to demonstrate that
      intertrochanteric osteotomy allowed improvement of late outcome after indentation
      fractures of the femoral head. PATIENTS AND METHODS: Between 1980 and 1984, four
      patients with a femoral head fracture after traumatic hip dislocation were
      treated by intertrochanteric osteotomy. The mean age at time of surgery was 24
      years. The injury was a traffic accident in 2 out of 4 cases. All of four had
      indentation fractures of the left femoral head. All patients underwent immediate
      reduction of the dislocation. The intertrochanteric osteotomy, was delayed
      between 1 months to 3 years. Four Muller's osteotomies and one Sugioka's
      osteotomy were performed. One patient had 2 successive procedures. Mean pre
      operative Merle d'Aubigne score was 13.5. In this retrospective study, results
      were assessed according to Merle d'Aubigne score and Epstein clinical and
      radiological method. RESULTS: Mean follow-up was 9 years (7 to 12). Three
      patients had a good result and one had two successive poor results in the same
      hip. Mean last follow-up Merle's score was 16.3 (15 to 18). The only poor result
      occurred because of late femoral head necrosis, in one hip with 2 successive
      osteotomies. DISCUSSION: As indentation fractures occurred in the upper part of
      the femoral head, the goal of the osteotomy was to displace the impacted
      articular surface out of the weight-bearing area. The prognosis of such lesions
      was usually poor, because in previously reported series, patients received no
      treatment. In our experience, intertrochanteric osteotomy could be proposed as an
      efficient therapy in femoral head indentation fractures.

PMID- 9775049
TI  - [Treatment of substance loss of the bones of the leg in traumatology by transfer
      of the free vascularized iliac crest. Apropos of 13 cases].
AB  - PURPOSE OF THE STUDY: Free iliac crest transfer as described by Taylor is an
      option for tibial bone reconstruction in traumatology. Our purpose was to
      evaluate results, bone reconstruction quality and delay for bone healing using
      microsurgical technique. MATERIAL: 13 men were operated on between December 1986
      and January 1994, mean aged 31 years (extreme 18-58) Bone lesion was localized at
      the middle third in 5 cases and at the lower third in 8 cases. The bone defect
      was directly related to traumatism in 2 cases, and secondary to resection of
      infected or necrotic bone in 11 cases. Limb neurologic and vascular problems have
      always been evaluated before reconstruction and amputation always been discussed.
      Preoperative limb arteriography showed only one major vessel of the limb in 6
      cases. Delay between injury and bone reconstruction averaged 11 months. METHODS:
      Bone debridement and bone stabilization by external fixator was performed on a
      first step. Resection of the fibula was performed to allow secondary compression
      at the reconstruction site. All necrotic and infected bone was "en bloc" resected
      using an oscillating saw. Bone reconstruction was performed in a second step when
      the wound was clean. Surgical team included a plastic surgeon for the micro
      surgical procedure and an orthopedic surgeon for bone fixation. Osteo-musculo
      cutaneous flap and osteo-muscular flap were used according to the size of the
      skin defect. Bone osteosynthesis was achieved by direct fitting after distraction
      applied by the external fixator. Vessel anastomosis was performed under
      microscope. RESULTS: One patient had to be amputated due to a lesion of a single
      vessel by an llizarov wire. In the remaining 12 cases, bone healing has been
      achieved after 10 months on average. Bone reconstruction averaged 8 centimeters.
      A secondary procedure has had to be performed in 9 cases. Two stress fractures
      have been observed. DISCUSSION: "Carcinologic" resection of infected bone is one
      of the key of this procedure, as described by Weiland. Many techniques had been
      described to treat traumatic bone defects. Papineau's technique is a long
      procedure and leads to instable scars on the leg. Use of cancellous bone covered
      with a free or a pedicled muscular flap gives good results, but it may appear
      logical to treat a composite defect with a composite graft. Progressive bone
      lengthening using Ilizarov technique is not an easy procedure among adults. Use
      of vascularized bone graft is known to be a good procedure for treatment of
      osteomyelitis, but this type of technique is technically demanding. Fibula
      transfers are useful especially when defect are more than 10 cm. long, but this
      bone is fragile and stress fractures are frequent. Iliac crest is closer to the
      tibia and appears to be a good donor site when bone defect is 5 to 10 cm. long.
      CONCLUSION: Free iliac crest transfer appears to be a reliable procedure for
      traumatic tibial loss ranging from 5 to 10 cm long although amputation must
      always be discussed in such difficult traumatic cases, especially if there is a
      posterior tibial nerve lesion.

PMID- 9775050
TI  - [Acute compartment syndrome in the post-traumatic leg].
AB  - PURPOSE OF THE STUDY: Compartment syndrome represents a clinical entity, whose
      diagnosis depends both on clinical findings as well as on measurement of the
      intracompartmental pressure. Physiopathology and clinical aspects of diagnosis
      and treatment of the acute compartment syndrome are discussed, based on the
      literature review and personal clinical experience. MATERIAL AND METHODS: We have
      based our experience on a series of 100 consecutive fractures of the leg, in
      which we studied mechanism of trauma, fractures localization, timing of surgery
      for fasciotomy and wound closure. RESULTS: The incidence of compartment syndrome
      was 8 per cent. Younger age (< 30 years), high energy trauma, or trauma occurring
      during physical activity appeared to increase the risk of occurrence.
      Localization of the fracture on the proximal, mid or distal thirds of the leg did
      not. DISCUSSION: The following aspects are discussed: 1) The perfusion pressure
      of a compartment is defined as the difference between the diastolic blood
      pressure and the intracompartmental pressure. 2) Fasciotomy is indicated whenever
      this value is inferior to 30 mmHg. 3) Failure to measure the pressure within 5 cm
      from the fracture site may cause underestimation of the compartment pressure. 4)
      Intramedullary nailing does not seem to increase the risk of compartment
      syndrome.

PMID- 9775051
TI  - [Fractures of the sacrum and neurologic lesions. Apropos of a case].
AB  - Sacral fracture is a difficult diagnosis due to the lack of specific signs and
      the inaccuracy of conventional radiology. This kind of fracture affects either
      polytraumatised or aged patients, in whom the fracture can be diagnosed. However
      these fracture have to be recognized because of their potentially adverse
      consequences, particularly on neurological structures. The case of a 56 years old
      man who fell from his height is reported. Two weeks later, due to mild neurologic
      symptoms, an X-ray and CT of the pelvis were performed, showing a fracture of
      both sacral alae. A complex neurologic sensitive and motor impairement appeared
      involving S1 to S5 levels on the left side and L2 to S5 levels on the right side.
      Many investigations were done to rule out any other etiologic factor of this
      complex and progressive neurologic deficit. The probable cause was an iterative
      stretching of the lumbosacral roots ambulating with a floating sacrum fracture.

PMID- 9775052
TI  - [A familial form of bilateral recurrent dislocation of the patella with major
      trochlea dysplasia].
AB  - PURPOSE OF THE STUDY: We report four cases of bilateral recurrent dislocation of
      the patella with major trochlear dysplasia, in the same family. MATERIAL AND
      METHODS: Details of clinical examination of all members of this family and
      measurements on knee radiographs are reported. RESULTS: In all cases a severe
      proximal dysplasia of the trochlea was described on lateral views. The patella
      and the trochlea had a normal shape on the axial view. DISCUSSION: In some
      recurrent dislocation, with no associated disease, possibility of a genetic
      transmission have been suggested in some publications. Cases involving the same
      family have never been reported to confirm a genetic transmission of a bilateral
      and major trochlear dysplasia. CONCLUSION: This report points out a genetic
      origin of severe trochlear dysplasia. To know more about transmission and
      chromosomic localisation, careful investigations on others families of bilateral
      dislocations with trochlear dysplasia must be done.

PMID- 9775053
TI  - [Apropos of, Subtrochanteric fractures. Comparative study of gamma nail and
      angular osteosynthesis with lateral cortical support].

PMID- 9775054
TI  - [Apropos of, Reconstruction of the anterior cruciate ligament by bone-patellar
      tendon-bone].

PMID- 9775056
TI  - [Orthopedic treatment of fractures of the lower extremity of the radius by the
      Judet technique. Anatomic results in function of the type of lesion: apropos of
      280 cases].
AB  - PURPOSE OF THE STUDY: The authors evaluated the anatomical results and limits of
      the conservative treatment for displaced Colle's fracture. MATERIAL AND METHODS:
      The anatomical results of 280 consecutive fractures were retrospectively
      analysed. Conservative treatment was performed according to Judet. Stability of
      the reduction was assessed for grade 0, 1, 2 of Kapandji's classification.
      Radiographical mean follow-up for all patient was three months (2 months to 8
      years). RESULTS: In 122 cases (64 per cent) mal-union was observed. Mal-union was
      due in 93.5 per cent of cases (114) to secondary displacement of the distal
      fragment and in 6.5 per cent (8 cases) to poor reduction. Secondary displacement
      was essentially posterior in the sagittal plane. The principal factors of
      instability were radial shortening superior to 3 mm (p = 0.005), patient age of
      55 years of more (p = 0.004), metaphyseal comminution (p = 0.004) and degree of
      primary displacement in the frontal plane (p = 0.01). Stability after reduction
      was determined by crossing the distal fragment in relation to the anterior cortex
      of the proximal fragment. There were 10.5 per cent algodystrophies and 9 per cent
      median nerve paresthesiae which were avoided by 45 degrees of wrist flexion.
      DISCUSSION: Judet's conservative treatment is indicated in extra-articular
      Colle's fractures (grade 0, 1, 2 of Kapandji's classification), after evaluation
      of factors of instability, secondary displacement and mal-union. Minor mal-unions
      may be well tolerated, and do not seem to affect wrist function with 3 mm of
      radial shortening and 10 degrees of radial glenoid posterior angulation on the
      sagittal plane.

PMID- 9775055
TI  - [C5-C6 and C5-C6-C7 traumatic paralysis of the brachial plexus of the adult
      caused by supraclavicular lesions].
AB  - PURPOSE OF THE STUDY: In C5-C6 and C5-C6-C7 brachial plexus palsies, prognoses
      was based on the recovery of a useful shoulder and elbow in order to control a
      normal or partially impaired hand. Treatment was an integrated procedure
      combining direct nerve surgery and muscle transfers. MATERIAL: Our study was
      performed on 27 cases of C5-C6 plexus palsy and 43 cases of C5-C6-C7 plexus palsy
      operated between 1984 and 1994, with an average delay between trauma and surgery
      of 8 months. METHODS: Elbow flexion was obtained by nerve surgery on the anterior
      part of the primary trunk or directly on the musculo-cutaneous nerve and after
      muscle transfer. Nerve surgery on supra-scapular nerve, on posterior part of
      primary trunk or directly on axillary nerve was also performed. RESULTS: The
      results were analyzed separately for shoulder and elbow flexion and globally. In
      C5-C6 palsies, elbow flexion was a goal which has been reached in 100 per cent of
      cases. Only 56 per cent of cases obtained a stable shoulder with active external
      rotation. In C5-C6-C7 palsies, elbow flexion was reached in 86 per cent of cases
      and stable shoulder with active external rotation only in 26 per cent.
      Reinnervation of the elbow flexors was reached by direct nerve surgery in 60 per
      cent of C5-C6 and 52 per cent of C5-C6-C7. Active external rotation was reached
      by spinal-suprascapularis nerve neurotization in 60 per cent of C5-C6 and 54 per
      cent of C5-C6-C7. DISCUSSION: No significant difference after nerve surgery for
      elbow flexion was found between C5-C6 and C5-C6-C7 plexus palsies. Failures of
      nerve surgery will undergo muscle transfer. When C7 is damaged, less muscles are
      transferable and results are less good. For shoulder, best results were obtained
      after spinal suprascapularis nerve neurotization with direct suture. In case of
      failure, a derotation osteotomy was performed. If shoulder was still unstable,
      transposition of the coracoacromial ligament to the humerus was also performed.
      CONCLUSION: In C5-C6 palsies, elbow flexion is a goal which must be reached in
      100 per cent of cases. Prognosis depends of shoulder function. In C5-C6-C7
      palsies, results are less good. 6 patients did not recover elbow flexion, no
      active mobility of the shoulder was observed in 63 per cent of them. The results
      obtained for elbow flexion are satisfactory if the program does not separate
      nerve surgery and muscle transfers.

PMID- 9775057
TI  - [Single-portal endoscopic treatment of carpal tunnel syndrome. Results of a
      preliminary series].
AB  - The aim of this study was to describe the single-portal endoscopic technique
      developed by J. Menon for the treatment of carpal tunnel syndrome and to evaluate
      its results in our first 82 patients. PATIENTS AND METHODS: The technique
      involved insertion of a split cannula into the previously dilated carpal tunnel,
      followed by section of the transverse carpal ligament from its proximal to its
      distal edge under visual guidance via a standard arthroscope. No immobilization
      was used postoperatively. A homogeneous population composed of 82 consecutive
      patients (71 female and 11 male) with a mean age of 51 years was studied. Mean
      follow-up was 15 months. A questionnaire was used to evaluate results at last
      follow-up, and patients were categorized into four groups based on Kelly's
      criteria. RESULTS: Fifty one patients (62 per cent) reported complete relief of
      symptoms and 29 (35 per cent) a substantial improvement, for a total of 97 per
      cent good and very good results. The symptoms remained unchanged in two patients,
      of whom one underwent revision. One patient was reoperated because of symptoms
      due to section of the thenar branch. The arthroscopic procedure was converted to
      an open procedure in 3.6 per cent of cases. DISCUSSION: The main advantage of the
      arthroscopic method is a faster recovery. The method developed by Menon and the
      material it requires are simple. Complications may be less common than with the
      two portal method. CONCLUSION: The single portal endoscopic technique developed
      by Menon for the treatment of carpal tunnel syndrome is effective and safe when
      it is performed in carefully selected patients using a faultless technique.

PMID- 9775058
TI  - [Combined fractures of the radius and the ulna at the elbow level in the adult.
      Analysis of 120 cases after more than 1 year].
AB  - PURPOSE OF THE STUDY: The purpose of this study was to increase the knowledge
      about these rare and serious injuries and to produce guidelines for a more
      successful ORIF. MATERIAL: 120 cases of combined fractures in adults with late
      results (minimum one year) stored in the AO Documentation-Center between 1979 and
      1989 were analyzed. Monotrauma was dominant, additional injuries were rare. No
      vasculo-nervous lesions were reported. 15 fractures were open. For the ulna 4
      fractures types were isolated, fractures of the coronoid process and the radial
      head (CR) 25 cases. Olecranon and radial head fracture (OR) 22 cases. Combination
      of anterior (coronoid) and posterior (olecranon) ulnar fracture with radial head
      fracture (COR) 41 cases. Metaphyseal ulnar and radial head fractures (MR) 32
      cases. For the radial head we have distinguished partial (61) and complete (59)
      fractures, the latter including 14 neck fractures. RESULTS: In the CR type
      indirect fixation technique was never perfect. Best results were obtained after
      ORIF of partial radial fractures. After resection, arthrosis (8/11) and valgus
      (8/11) were very frequent. In the OR type the stability was restored in simple
      fractures by the tension band technique even when the radial head was resected.
      In the severe COR type good results were rare. Arthrosis was important and
      frequent (36/41) especially after radial head resection. In the MR type ORIF of
      the radial head combined with ulnar plating gave the best results. Ulnar union
      was delayed or missing in 13 cases especially after radial head resection.
      Functional results after one year were better than expected on X-rays. This was
      due to immediate ORIF (92/120) and early mobilization. There were only 3
      infections and 2 reflex-dystrophies. DISCUSSION: The Coronoid is the key-fragment
      of the ulna. It is best reduced in CR-Type under vision by an anterior approach.
      In COR-lesions its reduction should be the first step of ulnar ORIF. Comminutions
      in OR, COR and MR-Types showed a high number of delayed or non union. The reason
      may be a biological weakness (reduced vascularization) in these areas. Therefore
      we advocate for bridging plates (and cancellous grafts) for the stabilization of
      such areas, especially for the metaphysis where a strong valgus force appears
      after radial resection. Radial head as the lateral pillar of the elbow should be
      restored by ORIF in partial fractures (excellent results) and even in complete
      fractures (5/10 excellent results) under favourable conditions. Prosthesis is
      indicated in severe radial comminution or serious ulnar instability.

PMID- 9775059
TI  - [Acetabular reconstruction using bone allograft in the revision of total hip
      prosthesis].
AB  - PURPOSE OF THE STUDY: Aseptic loosening of the acetabular component is the most
      worrying problem after hip arthroplasty. During revision surgery we prefer to
      rebuild a solid bony acetabulum close to the anatomy in which the implant will be
      cemented. On the basis of the first 48 acetabular reconstructions using deep
      frozen bony allografts, we carried out a review of our results in a pathology
      which will surely increase in the future. MATERIAL: 48 hips were operated
      according to this technique. It has been possible to review 38 of them, with an
      average follow-up of 7.3 years (extremes 5 years, and 9.6 years). The average age
      of the population at the time of surgery was 63 years. Two etiologies
      predominated: congenital hip dislocation sequelae and primitive hip arthritis. In
      10 cases of massive deterioration, a Muller's ring was used to stabilize the
      allograft. METHODS: The results were analyzed at 6 months, 2 years, 4 years, and
      at maximum follow-up, clinically, according to Merle d'Aubigne grading system.
      Radiologically, Ranawat's criteria were used to assess the re-centering of the
      reconstructed hips. The development of radiolucent lines and implants migration
      were also assessed. RESULTS: Clinically, the patients' comfort was always
      improved by pain relief. Radiologically, average acetabular upward migration of 5
      mm and medialisation of 3.5 mm were observed. 24 hips presented radiolucent
      lines. 19 radiolucent lines were below 2 mm. 5 were greater than 2 mm and leaded
      to loosening. In 4 of these 5 cases of radiolucent lines, there were acetabular
      migrations with failure. The radiological image remained stable afterwards. In
      these cases there was a real loosening, necessitating further surgery. In all
      cases, partial resorption of the graft was observed. DISCUSSION: Study of our
      first 38 cases shows that bony allograft and cemented acetabulum, sometimes
      including an armature, is one possible solution to the problem of difficult
      acetabular reconstructions. However, with an average follow-up of 7.3 years, we
      already have 5 (13 per cent) aseptic acetabular loosening, of which one has been
      operated on. Radiological analysis of these does not question the allograft, but
      rather imperfect re-centering. Analysis of the good results, 33 (87 per cent)
      stable acetabulum indicates re-fixing in quasi-anatomical position, in conditions
      close to those of a first time arthroplasty, with the aid of perfectly stabilized
      bony transplants, and where contact with the receiver acetabulum is maximal.
      CONCLUSION: Our follow-up is one of the longest in literature. But with a
      migration rate already of 13 per cent, it is not yet sufficient for us to be
      permanently assured about the future of our patients, even if their age is
      greater and their activity less than those of patients having a first hip
      arthroplasty.

PMID- 9775060
TI  - [Suture of the anterior cruciate ligament reinforced with carbon fibers. Anatomic
      results and articular degradation after 8-year follow-up].
AB  - PURPOSE OF THE STUDY: Osteoarthritis in anterior cruciate ligament (A.C.L.)
      deficient knees is reported by numerous authors, especially when conservatively
      treated. The aim of this study was to analyze at a longterm follow-up the outcome
      of these knees after surgical repair of an A.C.L. rupture augmented with carbon
      fibers. MATERIAL AND METHODS: Forty seven A.C.L. ruptures in 26 men and 21 women,
      whom mean sport level was low, had a surgical suture augmented with carbon
      fibers. The clinical and radiological results were analyzed at a mean follow-up
      of 8 years (6.2 to 10.8 years). RESULTS: At maximum follow-up, 64 per cent of
      patients had moderate pain in their operated knee and 11 per cent had major pain.
      The Lysholm score was 86.5. The "ARPEGE" functional cotation showed only 51 per
      cent excellent and good results. The mean anterior laxity was 12.8 mm. Sixty
      eight per cent of operated knees had no pivot shift. Eighteen knees (38 per cent)
      had femorotibial osteoarthritis and 23 (49 per cent) had femoropatellar
      osteoarthritis. The frequency and the level of osteoarthritis were correlated
      with the range of residual anterior laxity. CONCLUSION: Low sport level patients
      with A.C.L. deficient knee may have knee osteoarthritis. An effective correction
      of the anterior laxity, by any form of surgical treatment, seems indicated in
      these patients in order to prevent this articular degradation.

PMID- 9775061
TI  - [Percutaneous epiphysiodesis. Analysis of a series of 60 full-grown patients].
AB  - PURPOSE OF THE STUDY: Percutaneous epiphysiodesis is the actual treatment for
      mild leg length discrepancy. The authors discuss complications and efficiency of
      this technique and its accuracy for the prevision of leg length discrepancy.
      MATERIAL AND METHOD: We reviewed 60 skeletally mature patients (35 boys, 25
      girls). Limb length was defined by clinical and teleradiographic evaluation. Bone
      age was recorded using Sempe's and Pavia's atlas, using the hand, and
      Sauvegrain's method, using the elbow. Anticipated discrepancies and timing of
      epiphysiodesis were calculated using Hechard and Carlioz's graph. The
      percutaneous curetage was employed in all cases. RESULTS: The treatment was
      successful for all cases. Complications occurred postoperatively in 2 children
      who developed an hematoma. 10 children required a surgical revision: 2 cases had
      an inverted discrepancy, 4 patients were found to have limb deviation, and in
      four children this treatment was not adequate. The outcome was excellent in 48.3
      per cent of cases, satisfactory in 31.7 per cent, acceptable in 6.7 per cent and
      bad for 13.3 per cent of cases. DISCUSSION: Percutaneous epiphysiodesis is well
      tolerated in childhood with similar results to other techniques (stapling and
      Phemister's technique). Our experience suggest that:--complications are rare-
      this treatment is a satisfactory surgical solution--effective previsions for the
      best time for surgery have not yet been defined.

PMID- 9775062
TI  - [Fractures of the tibial pilon. Long-term retrospective study of 51 fractures
      treated with open reduction and osteosynthesis].
AB  - PURPOSE OF THE STUDY: Fracture of the tibial pilon is a rare injury and its
      treatment remains difficult. The aim of this study was to report the
      complications and long term results of internal fixation using a technique which
      respects soft tissues and in which little material was used. MATERIAL: From 1985
      to 1990, 48 patients with 51 fractures of the tibial pilon were treated by open
      reduction and internal fixation. All patients were submitted to a clinical and
      radiological review. METHODS: Both the Ruedi/Allgower and the AO-classification
      were used and determined by standard X-rays. Surgical procedure was performed
      with a 2 or 3 1/3 tube AO-plates and the peroneus was always fixed if fractured.
      Intraoperative reconstruction was analyzed. Subjective and objective scoring were
      used according to Olerud and Molander and the ankle arthritis was scored
      according to the classification determined by the SOFCOT in 1992. RESULTS: A
      minimal follow-up of 1 year for all cases was obtained, based on our own files.
      Thirty-eight patients (40 fractures) were evaluated after an average period of 88
      months (56 to 124 months). Five patients developed cutaneous infection, three
      developed deep infection and four developed superficial skin necrosis. One
      aseptic non-union necessitated reoperation after 14 months. Two ankles had joint
      fusion after 19 and 25 months respectively due to severe arthritis. In six cases
      infectious and non-infectious complications led to surgical revision. According
      to the Olerud and Molander score, 15 per cent of the results were excellent, 45
      per cent were good, 30 per cent were fair and 10 per cent poor. DISCUSSION:
      Literature shows a wide range of results following this surgical procedure. This
      is due to the difference in the type of trauma, classification system used,
      material used for the internal fixation and method of evaluation. The
      classification system of Ruedi and Allgower is the most commonly used but has a
      rather subjective tendency, especially between type II and type III. Treatment is
      difficult, especially for comminutive fractures associated with soft tissue
      damage. In this case, open reduction and internal fixation could increase
      iatrogenic lesions. For this reason surgical procedure can be delayed for several
      days, little material is used and soft tissue manipulation is reduced to minimum.
      In other study reports, the use of external fixation with or without minimal
      internal fixation have produced less complications without improving long term
      results. CONCLUSION: Analysis and comparison of study reports are difficult
      because of the absence of consensus in classification system and evaluation
      methods. The AO-classification, apparently the most objective, will probably be
      more and more used in the future. Treatment must be adapted to the bony lesion
      and soft tissue damage. Open reduction and internal fixation must be reserved for
      a specific group of lesion.

PMID- 9775063
TI  - [Amelioration of perioperative somatosensory evoked potentials in the surgery of
      injuries of the spine].
AB  - Somatosensory evoked potentials were performed in 38 patients with traumatic
      spine pre, per and postoperatively. In 3 cases, the S.E.Ps altered before
      surgery, were improved after decompression and reduction. This S.E.Ps improvement
      was associated to clinical improvement. Even though this study was carried out on
      few cases, it shows prognosis and diagnosis value of intraoperative S.E.Ps in
      traumatic spine surgery.

PMID- 9775064
TI  - [Transfer of posterior tibial muscle to the back of the foot: an original
      procedure for fixing the transplant].
AB  - PURPOSE OF THE STUDY: The purpose of the study was to adjust a palliative
      transfer using the Tibialis Posterior (TP) tendon in case of foot dorsiflexion
      palsy. The surgical procedure emphasized some functional features, in an attempt
      to lessen parasitical motion of the foot in abduction or in adduction when
      patients bear the ankle joint in dorsiflexion, and to strengthen the transfer.
      MATERIAL AND METHODS: The surgical technique was carried out four times in
      patients, with a follow-up of six to eighteen months. One 20 cm long leg
      incision, on the antero-lateral part of tibia, up to the retinaculum of extensors
      tendons, allowed a section of Tibialis Anterior (TA) tendon as proximal as
      possible, and an aperture through the tibiofibular fascia in its lower third. One
      15 cm long leg incision, along the postero-medial edge of the tibia, toward
      medial malleolus, allowed a release of the TP tendon after distal section. The
      tendon was rerouted across the former fascia aperture. One 6 cm foot medial
      incision face to navicular bone, where the TA tendon was thoroughly extracted and
      diverted, close to the sole side of the medial cuneiforme, and the two medial
      metatarsal bones. One 5 cm foot dorsal incision was performed, opposite to the 2d
      intermetatarsal space, where the diverted TA tendon end was recovered and pulled
      along a tunnel beneath the retinaculum of extensors. It was thus sutured, with a
      satisfactory tension to the TP tendon transferred across the tibiofibular fascia.
      Weight bearing in a short leg cast was allowed. RESULTS, DISCUSSION, CONCLUSION:
      In the four cases, the results fulfilled the goal, with a satisfactory evaluation
      of the efficacy of the transfer, even the TA tendon was once intentionally
      diverted through the 1st metatarsal space instead of the second one, without any
      damage for the vessels pedicle. Among the widespread use of TP tendon, we think
      that a more neutral position of the tendon should be adopted with a curse coming
      along the extension of the leg axis, to the 2d intermetatarsal space. The more
      distally the transfer may be bound, the much efficient it will be. Obviously,
      there is no change in a correct automatic use of the transfer in gait. Even
      though it requires more experience and much longer follow-up time, this technique
      ensure a reliable and comfortable attachment of the transferred tendon, by a
      tendon-to-tendon suture, and secure a better restored foot dorsiflexion.

PMID- 9775065
TI  - [Plantar dislocation of the tarso-metatarsal articulation (Lisfranc
      articulation). Apropos of a case].
AB  - Plantar fracture-dislocation of the tarso-metatarsal joint (Lisfranc plantar
      fracture-dislocation) is rather unusual. The authors described a case sustained
      in a 39 years old man injured in a motorcycle road traffic accident. Mechanism
      was recognized as plantar hyperflexion combined with an axial foot compression.
      Open reduction, and K-wires fixation were performed. An anatomical feature was
      restored. In an additional anatomical study on 8 cadavers, the plantar direction
      of a fracture-dislocation of the tarso-metatarsal joint was observed when the
      injury axis followed the scapho-cuneiform joint of the inner border of the foot
      and the cuboido-metatarsal joint on the lateral border, so that both tibialis
      muscles were fixed on the distal fragment. As tibialis posterior muscle is more
      powerful, the direction of the dislocation will be plantar. This type of injury
      is different from plantar fracture-dislocation of the tarso-metatarsal joint
      secondary to direct load bearing on the dorsum of the foot with severe skin and
      vessels injuries.

PMID- 9775067
TI  - [The value of doppler ultrasonography in Horton's disease].

PMID- 9775068
TI  - [The correlation between salivary endothelial expression of E-selectin and
      clinical and biological parameters in systemic scleroderma].
AB  - OBJECTIVES: A body of evidence suggests the pivotal role of endothelial cells in
      the pathophysiology of systemic sclerosis. E-selectin is an adhesion molecule
      specifically expressed by activated endothelial cells. In previous studies we
      noticed that E-selectin was frequently expressed in the salivary gland tissue of
      patients with systemic sclerosis. Moreover, E-selectin expression was detectable
      very early in the course of the disease. To better define the role of E-selectin
      in the pathogenesis of systemic sclerosis, we conducted a study aimed at
      determining whether E-selectin expression was correlated to clinical and
      biological features in patients with systemic sclerosis. METHODS: Thirty-one
      patients presenting with systemic sclerosis were included in the study. The
      following parameters were systematically assessed: duration and cutaneous extent
      of the disease, presence of secondary Sjogren's syndrome, antinuclear antibodies,
      and pulmonary and esophagus involvement. E-selectin expression was assessed by
      immunocytochemistry on minor labial salivary glands. RESULTS: E-selectin
      expression was detected in 21 out of 31 patients (67%). The disease duration was
      significantly shorter in patients with E-selectin expression (mean 9.1 +/- 8.5
      years versus 4.2 +/- 3.3 years, P < 0.05). No significant difference was found
      for other features. CONCLUSIONS: This study shows that endothelial E-selectin
      expression is mainly detectable early in the course of systemic sclerosis, when
      active and non-cicatrical sclerosis may be evidenced. No correlation was found
      between E-selectin expression and immunological disorders (antinuclear
      antibodies, secondary Sjogren's syndrome).

PMID- 9775069
TI  - [RS3PE: a clinical diagnosis, a prognosis more simple than its name].
AB  - INTRODUCTION: RS3PE syndrome (remittive symmetrical seronegative synovitis with
      pitting edema) was first described by MacCarthy in 1985. It is a rare type of
      seronegative polyarthritis occurring in the elderly. METHODS: Retrospective
      report of 13 cases (including eight male and five female patients; mean age 76.7
      +/- 3.7 years) and search for previously reported cases, using the Medline
      database. RESULTS: Pitting edema was present at onset of disease in nine cases.
      Joint arthritis was bilateral, occurring in the wrist (13 cases), shoulder (six
      cases), elbow (six cases), knee (six cases), ankle (four cases),
      metacarpophalangeal (four cases) and hip (one case). Radiographies were normal.
      Mean erythrocyte sedimentation rate was 62 +/- 19 mm at the first hour and mean C
      reactive protein level was 73 +/- 35 mg/L. Mild cholestasis was present in four
      of the seven patients for whom data were available. HLA B7 was present in five
      out of 12 cases (42%). Improvement was favorable, occurring over 7 months. Mean
      follow-up was 22.2 months. Fifty-nine other cases have been described in the
      literature. This syndrome, which affects the elderly, appears to be rare. Its
      clinical presentation is quite constant, with sudden onset, symmetrical
      polyarthritis and pitting edema. Its evolution, often long, is favorable.
      Rheumatoid arthritis and polymyalgia rheumatica are the main differential
      diagnoses. CONCLUSION: Due to its favorable outcome and the usefulness of a mild
      corticotherapy, this syndrome, though rare, should be diagnosed where necessary
      in elderly patients.

PMID- 9775070
TI  - [Cutaneous signs of Rickettsia and related microorganisms].
AB  - INTRODUCTION: Rickettsiosis are emerging, life-threatening infectious diseases
      that are world-wide distributed and have various manifestations. Most of the
      time, skin involvement is the prominent feature of clinical manifestations.
      Clinicians must therefore be well aware of these various clinical pictures.
      CURRENT KNOWLEDGE AND KEY POINTS: Knowledge about rickettsial infections has
      recently improved due to either the identification of new vectors and reservoirs,
      the description of new systemic and cutaneous signs and symptoms, or the
      amelioration of diagnosis methods. Cutaneous manifestations mainly depend on the
      type of microorganism and on the host characteristics. In some cases, they are so
      typical that their only identification would lead to the diagnosis. FUTURE
      PROSPECTS AND PROJECTS: As growing population movements may lead to an increase
      in the disease incidence, detailed knowledge of clinical, particularly cutaneous,
      manifestations of rickettsiosis is required in order to improve both diagnosis
      and treatment. When identified, cutaneous manifestations of rickettsiosis allow
      the clinician to confirm rapidly the diagnosis, using polymerase chain reaction
      or immunofluorescence and to institute prompt and specific treatment, thus
      reducing unfavorable disease outcome.

PMID- 9775071
TI  - [Hodgkin's disease in patients infected with the human immunodeficiency virus].
AB  - INTRODUCTION: Hodgkin's disease in patients infected by the human
      immunodeficiency virus (HIV) is still not part of the definition of acquired
      immune deficiency syndrome. Nonetheless, this entity has a particular
      presentation when compared to the disease occurring in immune-competent patients.
      CURRENT KNOWLEDGE AND KEY POINTS: Increased frequency (> 75%) of advanced
      anatomical stages and extranodular localizations (Ann Arbor system stages III and
      IV) has been outlined in HIV-infected patients. Mediastinal involvement is more
      unusual in immunocompromised than in immune-competent patients. The presence of B
      symptoms (fever, weight loss, nocturnal sweats) is very frequent. Finally, the
      predominance of mixed cellularity (type 3) characterizes Hodgkin's disease in
      immunocompromised patients. Due to either the immunodeficiency, antiretroviral
      treatments, poor hematological tolerance in response to chemotherapy, or to
      advanced anatomical stages, disease management may be hampered. Current
      therapeutical approaches often obtain complete remission; however, some deaths
      are still related to the disease progression to acquired immune deficiency
      syndrome. FUTURE PROSPECTS AND PROJECTS: From these observations, Hodgkin's
      disease management in HIV-infected patients relies on therapeutical approaches
      similar to those used for non infected patients, with some specific
      recommendations. Chemotherapy should be conducted in the shortest time in order
      to minimize chemotherapy-induced immunosuppression. Simultaneous use of
      antiretroviral treatment and reinforced opportunistic infection prophylaxis are
      of pivotal importance. Finally, the use of hematopoietic growth factors appears
      to be safe regarding viral replication, but still requires further evaluation.

PMID- 9775072
TI  - [Panhypopituitarism disclosing empty sella turcica syndrome].
AB  - INTRODUCTION: Empty sella syndrome is sometimes associated with anterior
      pituitary insufficiency, the latter being mostly partial or dissociated.
      EXEGESIS: We report a case of a profound panhypopituitarism revealing an empty
      sella syndrome. This case shows that empty sella syndrome, although a generally
      benign and asymptomatic condition, can be associated with hypopituitarism.
      CONCLUSION: In case of empty sella syndrome, especially if an endocrine
      dysfunction is clinically suspected, minimal hormonal analysis must be requested.

PMID- 9775073
TI  - [2 cases of iatrogenic oral streptococcal infection: meningitis and
      spondylodiscitis].
AB  - INTRODUCTION: The multiplication of invasive spine investigations for either
      diagnostic or therapeutical purposes increases the risk for iatrogenic
      infections. We report two cases of iatrogenic infections, one case of
      meningitidis and one case of spondylodiscitis due to Streptococcus viridans.
      EXEGESIS: The two cases included a 42-year-old male patient presenting with
      spondylodiscitis due to Streptococcus oralis following nucleolysis for discal
      node and a 51-year-old female patient with purulent meningitidis due to
      Streptococcus salivarius following hysteroscopy with spinal anesthesia. According
      to the disease chronology and bacterial results, iatrogenesis was evidenced. The
      streptococci originate from the patient's skin or from the operators' endobuccal
      flora. CONCLUSION: Simple aseptic rules, including wearing a surgical mask during
      any spinal tap, would definitely avoid iatrogenic infections.

PMID- 9775074
TI  - [A case of post-partum remission of acquired dyserythropoiesis, a rare cause of
      anemia in disseminated lupus erythematosus].
AB  - INTRODUCTION: Amongst the various causes of anemia in systemic lupus
      erythematosus, isolated and acquired erythrocyte dysplasia is rare and most often
      part of global dysmyelopoiesis. EXEGESIS: The authors report a case of acquired
      erythrocyte dysplastic syndrome that occurred in a 34-year-old woman in whom
      previous diagnosis had evidenced systemic lupus erythematosus of rather benign
      course. Other causes of dysmyelopoiesis were ruled out. Myeloid stem cell
      cultures showed selective inhibition of erythroid cells growing, with no
      particular effect of the patient's serum. While a corticosteroid treatment with
      prednisone (1 mg/kg/d) did not show any efficacy upon anemia, the patient's
      pregnancy was followed by prolonged correction of hemoglobin, making possible the
      tapering of prednisone down to 10 mg/d. CONCLUSION: Acquired erythrocyte
      dysplastic syndrome remains a rare cause of anemia in systemic lupus
      erythematosus. This case report suggests an immunological phenomenon, but the
      mechanisms underlying both the appearance and long-lasting remission after
      pregnancy remain unexplained.

PMID- 9775075
TI  - [An unusual distended abdomen].

PMID- 9775076
TI  - [Acute acalculous cholecystitis concurrent with varicella after bone marrow
      autograft].

PMID- 9775077
TI  - [Autoimmune cholangitis: a rare and ignored cause of cholestatic hepatitis].

PMID- 9775078
TI  - [2 cases of multiple autoimmune syndrome].

PMID- 9775079
TI  - [Pneumocystis carinii pneumopathy in rheumatoid polyarthritis treated by
      methotrexate in a patient with pulmonary asbestosis].

PMID- 9775080
TI  - [Chronic atrophic acrodermatitis and circulating anticoagulant].

PMID- 9775081
TI  - [Inflammatory response. Part 1].

PMID- 9775084
TI  - [Fever and polyarthralgia: a serology can obscure another...].

PMID- 9775083
TI  - [Invalidating and febrile spondylarthritis].

PMID- 9775085
TI  - [Deficiencies of the heart and neurons...].

PMID- 9775086
TI  - [Abscess waltz in a patient with a kidney transplant].

PMID- 9775087
TI  - [An unjustified hysterectomy?].

PMID- 9775088
TI  - [In the month of May, do whatever you please...].

PMID- 9775089
TI  - [Skin of lizard, skin of chagrin].

PMID- 9775090
TI  - [A diagnosis of sciatica cut to pieces...].

PMID- 9775091
TI  - [A feminist poem: searching for the author].

PMID- 9775092
TI  - [A big-hearted lupus].

PMID- 9775093
TI  - [Down the claws!].

PMID- 9775094
TI  - [An unexplainable recurring hepatitis with transient discomfort: no, it is not
      yet a new virus!].

PMID- 9775095
TI  - [Between the infection and the vaccine, one must choose].

PMID- 9775096
TI  - [Periarticular inflammation in a hemodialyzed diabetic patient].

PMID- 9775097
TI  - [An adrenal tumor caused by the bite of worms].

PMID- 9775098
TI  - [A obscure history...].

PMID- 9775099
TI  - [A recalcitrant hypercalcemia].

PMID- 9775100
TI  - [Recurrent febrile organomegaly].

PMID- 9775101
TI  - [A very silent hematopulmonary syndrome...].

PMID- 9775103
TI  - [A diagnosis of drumstick].

PMID- 9775102
TI  - [Apropos of a single bout of renal insufficiency, severe but regressing].

PMID- 9775104
TI  - [The uterus does not explain everything].

PMID- 9775105
TI  - [A very mysterious skeleton].

PMID- 9775106
TI  - [Difficult headaches].

PMID- 9775108
TI  - [No, it's not the appendix!].

PMID- 9775107
TI  - [An ill tongue...].

PMID- 9775109
TI  - [Doctor Martin is very sick...].

PMID- 9775110
TI  - [1998: internal medicine on the Internet].

PMID- 9775111
TI  - [Peripheral adrenal insufficiency in AIDS].
AB  - BACKGROUND: Lesions of adrenal glands are common findings at autopsy of patients
      with acquired immunodeficiency syndrome (AIDS). In contrast the diagnosis of
      symptomatic adrenal insufficiency is rarely established during the lifetime of
      these patients. PATIENTS: We report four new cases and review the literature. All
      four patients had full blown AIDS with a mean CD4 cell count of 19 mu/L. One or
      more opportunistic disease was present at the time of diagnostic: cytomegalovirus
      retinitis in two cases, disseminated Mycobacterium avium infection in two,
      Kaposi's sarcoma in two and Candida esophagitis in one. RESULTS: The clinical
      presentation constantly included fatigue, weight loss, severe orthostatic
      hypotension and gastrointestinal disturbances. Cutaneous hyperpigmentation was
      present in three cases. In most cases biological abnormalities were typical, such
      as hyponatremia, urinary Na/K ratio > or = 1, and hyperkalemia. Serum cortisol
      levels were within the range of normal in three cases but response to the
      cosyntropin challenge was typically impaired in all cases. Clinical and
      biological manifestations returned to normal in 1 to 3 weeks after initiation of
      therapy with cortisol, associated to fludrocortisone in three cases. However, 13
      months after diagnosis, three patients were dead. CONCLUSION: Usually
      asymptomatic, diagnostic of symptomatic adrenal insufficiency must be suspected
      even when clinical presentation is atypical because rapid efficiency of hormonal
      treatment.

PMID- 9775112
TI  - [Homocysteine, 5,10-methylenetetrahydrofolate reductase and deep venous
      thrombosis. Survey of 120 patients in internal medicine].
AB  - BACKGROUND: In the last few years, the association of deep vein thrombosis with
      frequent biological risk factors and genetic polymorphisms has significantly
      modified the field of venous thrombosis. In this study, we measured plasma
      homocysteine levels and tested the C677T methylenetetrahydrofolate reductase
      (MTHFR) mutation. PATIENTS AND METHODS: Plasma homocysteine levels and test for
      C677T MTHFR mutation were performed in 120 consecutive patients with objectively
      diagnosed deep vein thrombosis, and in 120 controls. RESULTS: We found a strong
      association between hyperhomocysteinemia and thrombosis (odd ratio: 2.43 IC 95%
      [1.27-4.7]). Conversely the C677T MTHFR gene polymorphism is only associated with
      hyperhomocysteinemia but not associated with thrombosis. CONCLUSION: This is a
      preliminary study to the ongoing international multicentric study of SNFMI
      (Societe nationale francaise de m0+edecine interne) concerning
      hyperhomocysteinemia and venous thrombosis.

PMID- 9775113
TI  - [Buerger's disease or thromboangiitis obliterans].
AB  - PURPOSE: To review clinical data, pathophysiology and treatment of
      thromboangiitis (Buerger's disease). DATA SYNTHESIS: Buerger's disease or
      thromboangiitis obliterans (TAO) is an obliterative vascular disease that affects
      medium and small sized arteries as well as superficial veins. Young males and
      smokers are preferentially afflicted with the disease. TAO accounts for 0.5 to 5%
      of occlusive vascular disease. Though TAO has a world-wide distribution, it can
      be found with greater prevalence in Eastern Europe, the Mid-East, Asia, and
      Southeast Asia. Women account for 10 to 20% of the patients and 5 to 10% are more
      than 60-years-old. Approximately 95% are smokers and disease activity is strongly
      associated with the use of tobacco. The pathogenesis is poorly understood and
      most hypotheses are controversial. There is no specific marker of the disease and
      the diagnosis is based on clinical and angiographic criteria. The disease
      spontaneously leads to tissue loss and major amputations. This can generally be
      avoided by discontinuing smoking. Induced hypervolemia and prostacyclins are
      effective treatments of critical limb ischemia in TAO. CONCLUSION: If
      pathophysiology is still poorly understood, spontaneous evolution can be avoided
      by stopping tobacco and prostacyclin.

PMID- 9775114
TI  - [Infectious endocarditis on permanent endocavitary stimulation leads: apropos of
      2 cases].
AB  - BACKGROUND: Permanent endocavitary pacemaker lead infectious endocarditis is
      rare. Two new cases are reported. CASE REPORTS: The first case appeared in a 63
      year-old white woman with a permanent endocavitary pacemaker for 3 years. It was
      caused by Streptococcus bovis, unique to this pathology. The second case was
      caused by Streptococcus epidermidis in a diabetic 72-year-old woman. In these two
      cases, the clues to the diagnosis were hemocultures and transesophageal
      echocardiography. CONCLUSION: These two cases emphasize the importance of
      transesophageal echocardiography (TEE) for diagnosis and for driving treatment.
      Treatment is based on appropriate antibiotics and pacemaker removal. In the
      second, case, the material was surgically removed under cardiopulmonary bypass
      because of the size of the infection.

PMID- 9775115
TI  - [A rare dyspnea in internal medicine: platypnea-orthodeoxia after pneumonectomy].
AB  - BACKGROUND: A right-to-left shunting across a patent foramen ovale is a rare
      cause of acute respiratory failure after pneumonectomy. CASE REPORTS: We report
      two cases of posture dependent dyspnea (platypnea-orthodeoxia) secondary to
      postoperative right-to-left shunting across a patent foramen ovale. Both cases
      occurred three months after pneumonectomy, the first in a 63-year-old man and
      other in a 52-year-old man. CONCLUSION: A platypnea-orthodeoxia (dyspnea induced
      by the upright position with arterial deoxygenation relieved by recumbency)
      should lead to the diagnosis which is confirmed by echography or cardiac
      catheterization. The prognosis is good after surgical closure of the patent
      foramen ovale. The physiopathologic mechanism is poorly understood. We report two
      cases of platypnea-orthodeoxia.

PMID- 9775116
TI  - [Association of Biermer's anemia and gastric carcinoid tumors].
AB  - BACKGROUND: The occurrence of gastric carcinoid tumors during the cure of
      pernicious anemia has been reported in the literature. Concerning a new case, we
      review physiopathological data of this infrequent association. CASE REPORT: We
      report the case of a 47-year-old women with pernicious anemia in which
      gastroscopy found two small tumors developed from enterochromaffin-like cells.
      CONCLUSION: These tumors are usually latent and developed from enterochromaffin
      like cells. The pathologic and histologic diagnosis is based on positive
      chromogranin A immunomarking. The physiopathological mechanism studies are in
      favour of the predominant part of hypergastrinemia following achlorhydria.
      Usually, evolution is benign and surgical or endoscopic resection recommended.

PMID- 9775117
TI  - [Pseudotumorous presentation of neuro-Behcet: role of the withdrawal of
      colchicine?].
AB  - BACKGROUND: Neurological involvement occurs in 10 to 28% of patients with
      Behcet's disease. CASE REPORT: We report a case of neurological pseudotumoral
      presentation of Behcet's in a patient with a long standing disease treated with
      low dose of prednisone and colchicine (1 mg/day), 2 months after withdrawal of
      colchicine. CONCLUSION: Neurological manifestations during Behcet disease can be
      secondary to direct central nervous system involvement (encephalitis,
      encephalomyelitis) or vascular angitis (essentially cerebral venous thrombosis
      and, rarely, intracranial aneurysms). Neurological pseudotumoral presentation is
      rarely reported.

PMID- 9775118
TI  - [Treatment of Guillain-Barre syndrome in adults: role of plasma exchange].
AB  - PURPOSE: To review recent data on treatment of Guillain-Barre syndrome,
      especially indications of plasma exchange. DATA SYNTHESIS: Guillain-Barre
      syndrome is the most common cause of acute flaccid paralysis. The current
      mortality is 5%, sever motor sequelae persist after 1 year in 10% of cases.
      Multidisciplinary teams are required to treat these patients, trained to all
      specific treatments. Oral and intravenous steroids have proven ineffective. Two
      large randomized clinical trials comparing plasma exchange (PE) with no treatment
      have shown a short-term and a 1-year benefit. Appropriate number of exchanges and
      indications are now more precisely known. In mild form (walking possible),
      patients should receive two PEs. A further two exchanges should be done in case
      of deterioration or in advanced forms (loss of walking ability, mechanical
      ventilation). More exchanges are not beneficial. Recently two new randomized
      trials have produced evidence that intravenous immune globulin (IVIg) (0.4 g/kg/d
      for 5 days) were as effective as five PEs in advanced forms. The combination of
      PE with IVIg did not confer a significant advantage, while increasing cost and
      risks. CONCLUSION: The combination of PE with IVIg did not confer, in advanced
      forms, the choice between PE and IVIg depends of the contra-indications of each
      treatment.

PMID- 9775119
TI  - Des phaneres insolites.

PMID- 9775120
TI  - [Seasonal factor and Horton's disease].

PMID- 9775121
TI  - [Medical emergency and the elderly: from internal medicine to geriatrics].

PMID- 9775122
TI  - [A sociomedical geriatric assessment in the emergency units: an alternative to
      the hospitalization of aged patients?].
AB  - BACKGROUND: Elderly patients admitted to the emergency unit are usually
      hospitalized in medical units. Could a gerontologic evaluation in the emergency
      room lead to another solution than hospitalization? METHODS: Since January 1993,
      a sociomedical geriatric reception has been operating in the emergency unit of
      the university hospital in Brest, France, every day from 10 AM. to 6 PM. Patients
      older than 75 years, dependent or at risk of dependence are examined by a
      geriatrician. The medical situation is evaluated. The nutrition status, the
      cognitive functions, the thymic functions, the gait, and the functional abilities
      are systematically studied. In the same time the social evaluation is realised by
      a social worker. RESULTS: From January 1993 to December 1996, 1,514 patients have
      been cared for by the social medical team. Once the assessment of each patient
      was made only 49% of them actually had to be hospitalized in a medical
      department. The outcome of 100 patients discharged between January 1994 and June
      1994 was evaluated one year after their discharge at home, 11 patients were
      rehospitalized. The reason for rehospitalization were different from the reasons
      for the first hospitalization. CONCLUSION: A gerontologic assessment in the
      emergency room permits to avoid hospitalization in 50% of the cases. One year
      after discharge at home only 11% of the patients were rehospitalized.

PMID- 9775123
TI  - [Tuberculosis and systemic diseases. Apropos of 16 cases].
AB  - METHODS: We analyzed retrospectively 16 patients between 1976 and 1993 (six men,
      ten women, mean age: 49-year-old) suffering from connectivitis. HIV-negative and
      receiving corticosteroids, combined for six of them with immunosuppressive
      therapy, and suffering from tuberculosis. RESULTS: The mean period between first
      signs and diagnosis was 51 days (3-190 d). Tuberculosis was pulmonary (n = 10) of
      which 4 miliary, pleurisy (n = 3), lymphadenitis (n = 5). We only observed one
      meningitis, one otitis and one female genital tuberculosis. Six patients had more
      than one localisation. Diagnosis was proven bacteriologically eight times,
      histologically six times and for three patients diagnosis was certain because of
      efficacy of antituberculosis antibiotherapy. Evolution was always good, with
      antituberculosis antibiotherapy of maximum 18 months, without sequella. Because
      rifampicin enzymatic induction, connectivitis worsened in five patients. An
      increase in corticotherapy was necessary for these five patients. CONCLUSION:
      This series confirmed the frequently extrapulmonary feature of tuberculosis in
      immunosuppressed patients, the long delay of diagnosis and the risk of
      exacerbation of underlying disease with rifampicin.

PMID- 9775124
TI  - [Potential importance of antileukotrienes in the treatment of asthma and other
      inflammatory diseases: apropos of a new pharmacological class].
AB  - OBJECTIVES: Among the mediators involved in the asthma bronchoconstriction and
      inflammation mechanisms, there is now substantial evidence that the
      sulfidopeptide leukotrienes (LTs) are important. Antagonists of their receptors
      and inhibitors of their synthesis have been developed. IMPORTANT POINTS:
      Antagonists of LTs, as well as inhibitors of their synthesis, reduce the LTs
      actions: bronchoconstriction, bronchial hyperresponsiveness, hypersecretion and
      inflammation. They produce an acute bronchodilating effect in mild asthma, reduce
      the hyperresponsiveness responses due to allergens, aspirin and cold and dry air,
      and also cutaneous and gastrointestinal reactions. Oral administrations tested
      during 4 or 6 weeks diminish the use of the beta-agonists, decrease the asthma
      symptom scores and other inflammatory signs. PERSPECTIVES AND PROJECTS: More
      studies for longer periods, double blind trials and comparisons with classical
      treatments will be necessary to define the real place of LTs antagonists in the
      treatment of asthma. So their efficacy has to be confirmed as well as their good
      tolerance profile (particularly for hepatic functions). CONCLUSION: Antagonists
      of receptors and synthesis inhibitors of LTs have known a recent and important
      development. They constitute a new therapeutic class: further studies are needed
      to better define the place of these new drugs in the treatment of asthma and
      other inflammatory diseases.

PMID- 9775125
TI  - [Hexose transporters in humans: their role in insulin sensitivity of peripheral
      tissues].
AB  - OBJECTIVES AND JUSTIFICATION: To describe facilitated diffusion glucose
      transporters (GLUT) in humans, and particularly the regulation of GLUT4
      expression since it is predominantly responsible for insulin-mediated glucose
      transport in muscle and adipose tissue, and plays a crucial role in whole-body
      glucose homeostasis. MAIN POINTS: Numerous studies have shown abnormal expression
      of GLUT4 in insulin responsive tissues in diabetes mellitus and other insulin
      resistant states. The recent development of transgenic mice that overexpress
      GLUT4 in muscle, adipose tissue, or both has also emphasized the importance of
      GLUT4 in glucose homeostasis. PERSPECTIVES AND PROJECTS: The studies performed in
      transgenic mice suggest that strategies to increase GLUT4 transporters in insulin
      responsive tissues may lead to new therapeutic possibilities to improve insulin
      sensitivity in insulin resistant states such as non-insulin-dependent diabetes
      mellitus. CONCLUSIONS: Glucose transport is a crucial process in mammals, which
      needs specific transmembrane hexose transporters. Each transporter is important
      in the regulation of glucose homeostasis. Advances in the knowledge of both the
      action and the regulation of the glucose transport system may provide new
      insights for the development of therapeutic interventions in diseases such as
      obesity or diabetes mellitus.

PMID- 9775126
TI  - [Papillary fibroelastoma. A rare etiology of strokes in young patients].
AB  - BACKGROUND: The papillary fibroelastomas are cardiac lesions, which typically
      occur on the cardiac valves, but rarely on the endocardium. The incidence of
      these benign primitive tumors varies from 0.002 to 0.33% and increases with
      advancing age. METHODS: We report two cases of stroke, one in a 31-year-old man
      and the other in a 48-year-old woman, both admitted to the same stroke center.
      RESULTS: The diagnostic studies were normal in these two patients, except for the
      echocardiography. The first showed an echogenic mass on the mitral valve on
      transthoracic echocardiography (TTE), confirmed by the transesophageal
      echocardiography (TEE). The second demonstrated a mass on the sigmoid aortic
      valve on TEE, but the TTE was normal. For these two patients, a surgical excision
      was carried out and pathologic examination concluded to a papillary
      fibroelastoma. After surgery, no recurrence was observed. CONCLUSIONS: The
      papillary fibroelastomas are usually asymptomatic and easily detected by TEE.
      However, it can be revealed by stroke, myocardial infarction and lower limbs
      ischemia. These cardiac tumors should be surgically removed, since their complete
      excision remains the only means of avoiding a recurrence of embolism.

PMID- 9775127
TI  - [Endoscopic treatment of subcutaneous fat necrosis secondary to pancreatic
      vascular fistula: apropos of a case].
AB  - PATIENT AND METHOD: We report the case of a 68-year-old man who presented a
      pancreatic tumor with a pancreato-vascular fistula and a Weber-Christian
      syndrome. Pancreatic enzymes levels at the admission were high: amylasemia 2,470
      IU/L (N < 110) and lipasemia 11,700 IU/L (N < 220). The treatment consisted in
      total parenteral nutrition and somatostatin (100 micrograms x 3/day). Because we
      noted neither clinical nor biological improvement after 10 days of treatment, we
      performed an endoscopic retrograde pancreatography. During this examination, we
      put a 7 French diameter prosthesis through the Wirsung stenosis. RESULTS: No
      problem arose after endoscopy: since the day after the endoscopy, pancreatic
      enzymes decreased by half and become normal in 4 days; arthralgias and cutaneous
      injuries, both caused by cytosteatonecrosis, disappeared respectively in 5 and 10
      days. There is no evidence of subsequent recurrence after 3 months of follow-up.
      CONCLUSION: Pancreatic endoscopic prosthesis can replace the surgical treatment
      of pancreato-vascular fistula with a good efficacy.

PMID- 9775128
TI  - [Acute disseminated encephalomyelitis preceding cutaneous lupus].
AB  - STUDY DESIGN: A case of acute disseminated encephalomyelitis (ADEM) preceding the
      features of cutaneous lupus is reported. OBJECTIVES: To suggest that ADEM and
      cutaneous lupus are pathophysiologically related. SUMMARY OF THE BACKGROUND DATA:
      Neurological complications of systemic lupus erythematosus are common. However,
      demyelinative central nervous system manifestations are rare, and restricted to
      neuromyelitis optica (NMO). NMO is thought to be a partial form of ADEM. METHODS:
      A clinical, neuroradiological and immunological study was performed in this case.
      RESULTS: ADEM was diagnosed in a young black female. Three years later, she
      developed a cutaneous lupus without hypocomplementemia. CONCLUSION: A
      relationship between ADEM and cutaneous lupus is suggested. The normal serum
      complement level in our patient might be a predisposing factor for the
      development of ADEM.

PMID- 9775129
TI  - [Occupational exposure to cadmium and renal cancer. Apropos of a case].
AB  - INTRODUCTION: Cadmium is a carcinogenic substance and bronchial and prostatic
      cancer may be readily identified as professional diseases. It is also a
      nephrotoxic substance but renal carcinoma are rarely imputed to this kind of
      intoxication. CASE REPORT: We report the observation of a 59-year-old woman with
      a long unprotected professional exposure to cadmium. She developed an epidermoid
      carcinoma of the kidney and later of the lung. Levels of cadmium in blood samples
      were abnormally high, confirming the existence of a chronic impregnation.
      CONCLUSION: We have judged cadmium to be responsible for her renal disease: the
      fact of a long unprotected professional exposure, the scarcity of renal
      epidermoid carcinoma, the well established nephrotoxicity of this substance and
      the association with other cancers, appear to us as convincing evidence, and the
      kidney cancer of our patient has been considered a professional disease.

PMID- 9775130
TI  - [Adult-onset Still's disease after hepatitis A and B vaccination?].
AB  - BACKGROUND: Hepatitis A and B vaccination are generally very well tolerated.
      However, exceptional cases of arthritis and systemic diseases have been reported
      after hepatitis B vaccination. CASE REPORT: The authors report a case of adult
      Still's disease apparently triggered by hepatitis A and B vaccination. The
      patient was a 38-year-old woman who presented with fever, hepatitis, pneumonitis
      and neurologic symptoms, compatible with the diagnosis of adult Still's disease.
      DISCUSSION: The authors discuss the rarity of systemic diseases triggered by such
      vaccination, the link between hepatitis B virus and some vasculitis, and the
      possibility for viral bacterial infections to trigger adult Still's disease.

PMID- 9775131
TI  - [Needles in the heart].

PMID- 9775132
TI  - [Amoxapine-induced pseudopheochromocytoma. Apropos of a case].

PMID- 9775133
TI  - [Aseptic meningitis during treatment with very low doses of intravenous
      immunoglobulins].

PMID- 9775134
TI  - [Antiplatelet antibodies].

PMID- 9775135
TI  - [Genetic screening of hemochromatosis].

PMID- 9775136
TI  - [Hypocholesterolemia during the acute phase of an inflammatory reaction of
      infectious origin. 120 cases].
AB  - OBJECTIVES: Transitory changes in the plasma levels of lipids, cholesterol and
      triglycerides have been observed since a long time by many authors, in the course
      of bacterial infections, with hypocholesterolemia, hypertriglyceridemia in the
      acute phase, increasing the third day of clinical evolution. Their decrease
      accompanies the return to normal. Lymphopenia is also observed during bacterial
      infections and as the very low level of cholesterol, is considered to be a factor
      of critical prognosis, predicting an unfavorable evolution, essentially in
      elderly people. C-reactive protein (CRP) proves to be a good marker protein in
      inflammation due to sepsis; its synthesis is directly influenced by the cytokines
      released during the acute phase response of inflammation in bacterial infection.
      The authors are researching a correlation between the intensity of the acute
      phase response represented by CRP levels, and a reduced cholesterol level, or a
      hypertriglyceridemia, or lymphocytopenia. METHODS: In this prospective study,
      blood samples at fasting state were obtained in 160 patients divided into four
      groups of 40 according to CRP levels, including a witness group (CRP levels lower
      than 10 mg/L) and three groups of patients presenting infectious diseases with
      acute phase response of different intensities. All patients were checked for
      cholesterol, triglyceride and CRP levels, blood cell count. The three pathologic
      groups were compared to the witness group and to each other. RESULTS: A
      significant correlation was established between the intensity of the acute phase
      response during sepsis and reduced levels of cholesterol. Cholesterolemia was
      reduced (P < 0.05) in all three pathologic groups when compared to the witness
      group; the difference existed when a low intensity inflammatory response was
      observed (mean CRP level 27.6 (10.5) mg/L in group 1). Moreover a significant
      response exists with reduced cholesterol levels between group 4 (mean CRP level
      250 (73) mg/L) and group 1. Lymphocytopenia was observed in all three pathologic
      groups, without evident link with the CRP levels. No modification was observed
      concerning triglyceride levels. CONCLUSIONS: The authors report a negative
      correlation of total cholesterol to CRP levels at the early stage of infections
      diseases. Prior studies established a negative correlation between inflammatory
      parameters during bacterial infections and total cholesterol and HDL fraction.
      Considering the plasma lipid pathways, HDL fraction plays a major role in lipid
      transport and exchanges between lipoproteins, thanks to its apolipoproteins A1,
      A2 and C. IL-1 and TNF, two cytokines involved in the acute phase response, have
      metabolic functions which could possibly contribute to reduce plasma total
      cholesterol and HDL2 fraction. IL-1 also induces lymphocytopenia. The authors
      propose the hypothesis of a correlation between plasma cholesterol levels and the
      acute phase response during sepsis, which could be induced by the mediators or
      effectors of inflammation.

PMID- 9775137
TI  - [Frequency of autoimmune diseases in 218 patients with autoimmune thyroid
      pathologies].
AB  - PURPOSE: The aim of our study was to investigate the frequency of auto-immune
      diseases in patients suffering from autoimmune thyroid diseases. METHOD: We
      realised a retrospective study from 1981 to 1993 including 218 patients suffering
      from thyroiditis who were followed in the same hospital service. There were 202
      women and 16 men with a mean age 49 at the moment their thyroid pathology was
      discovered. RESULTS: Thirty patients had one or more autoimmune disease
      associated to their thyroid disorders, representing 13.7% of total patients. The
      two most frequent autoimmune diseases were lupus and Sjogren's syndrome. In 17
      cases the diagnosis of the associated autoimmune disease was made simultaneously.
      The systemic disease preceded with an 8-year delay the thyroid disease in five
      cases, and the thyroid disease was annunciatory in eight cases with a delay of 5
      years. The frequency of autoimmune diseases seems to be higher in patients
      suffering from thyroid disorders than in the general population. They are
      probably common physiopathological mechanisms. CONCLUSION: The frequency of these
      associations suggests the need for a long-lasting survey of those patients having
      thyroid disorders. Initial evaluation and a regular checking in patients
      suffering from an autoimmune disease is recommenced.

PMID- 9775138
TI  - [Cholesterolemia and pathology: update].
AB  - The relationship between plasma cholesterol levels and disease is more complex
      than presumed. If the pathogenic role of hypercholesterolemia in ischemic
      myocardial disease is now undoubted, the deleterious effect of
      hypocholesterolemia induced by diet or drugs, mainly on cancer mortality and
      violent death, is still controversial. In a prognostic point of view it seems
      that the degree of diminution of cholesterol levels is more important than
      hypocholesterolemia itself. Several hypothesis were formulated; however,
      hypocholesterolemia does not appear as a causal factor. A prudent approach of
      hypercholesterolemia remains desirable but without special alterations of the
      recent recommendations concerning the management of hypercholesterolemia.

PMID- 9775139
TI  - [Rare hyperimmunoglobulinemia E syndromes].
AB  - Total immunoglobulin E levels are very frequently measured, particularly for
      allergy. Their high levels are ordinarily found in atopy and parasitosis. This
      article subject is to determine rare diseases where high levels of total
      immunoglobulin E are found except in classic diseases. These rare hyper
      immunoglobulin E syndromes are more often associated with immunologic deficiency
      more or less intense that lead to viral, fungal and bacterial infections. Buckley
      syndrome: deep infections due to Staphylococcus aureus, chronic dermatitis.
      Netherton disease: cutaneous and hair disease, allergic manifestations. Wiskott
      Aldrich syndrome: thrombocytopeny and -pathy, dermatitis. Di-George disease:
      hypoparathyroidism, infections. Selective deficit of immunoglobulin A: recurrent
      infections. It is difficult to differentiate between atopic dermatitis and
      Buckley syndrome and Netherton disease because of eczematiform chronic dermatitis
      and high-levels of total immunoglobulin E found in all these diseases.

PMID- 9775140
TI  - [Recurrent Miller Fisher syndrome and anti-GQ1b antibodies].
AB  - INTRODUCTION: Miller-Fisher syndrome is defined by the triad: ophthalmoplegia,
      ataxia and areflexia. This rare entity is generally regarded as a variant of the
      Guillain-Barre syndrome, although neurophysiological patterns differ. In the
      acute phase of the disease, sera of affected patients contain high titers of
      antiganglioside anti-GQ1b, which is a specific marker. Recurrences are
      exceptional. EXEGESE: We report the case of a man with three recurrences of
      Miller-Fisher syndrome within 16 years. Anti-GQ1b antibody titers were elevated
      during an episode, decreasing but not completely and vanishing 2 years later.
      Intravenous human immunoglobulin treatment probably accelerated improvement at
      the two last episodes. CONCLUSIONS: Some experimental and immunohistochemical
      data from the literature argue for a probable direct pathogenic role of
      antibodies against GQ1b ganglioside in this syndrome. This should be a rationale
      for the use of immunomodulating treatments.

PMID- 9775141
TI  - [Langerhans histiocytosis in adults: cutaneous and mucous lesion regression after
      treatment with thalidomide].
AB  - BACKGROUND: Langerhans cell histiocytosis is a rare disorder with a wide spectrum
      of diseases and various clinical behaviours. The prognosis depends on the
      patient's age at onset and the extension of the disease. Treatment is function of
      evolution and extension of the disease. CASE REPORT: We report one case of
      Langerhans cell histiocytosis in a 33-year-old woman with resistant vulvar
      involvement whose cutaneous lesions improved with thalidomide. Complete healing
      of the genital lesions occurred within 1 month, but the patient discontinued her
      treatment after 3 months because of somnolence. Recurrence of the symptoms was
      observed within 2 weeks without treatment, but complete control was obtained with
      reintroduction of thalidomide. No severe adverse effect was detected at
      electrophysiological and clinical examinations. CONCLUSION: The simplicity and
      the rapid effect of thalidomide on cutaneous lesions suggest that new clinical
      evaluation of this old drug that can also be used in some systemic disease might
      be of the value.

PMID- 9775142
TI  - [Familial sarcoidosis: three case reports].
AB  - INTRODUCTION: Familial sarcoidosis is rare. We reviewed 147 cases of sarcoidosis,
      whatever their localization, diagnosed at Rabat-Sale University Hospital, during
      a period of 10 years (1983-1993). Among these cases, we report those of three
      patients with sarcoidosis, in a same family. The observations concern three
      generations. OBSERVATIONS: Observation 1: the grandmother presented with
      pulmonary sarcoidosis. Observation 2: the mother presented with sarcoidosis of
      the skin, joint and lung. Observation 3: the daughter had cutaneous and pulmonary
      localizations. DISCUSSION: The real frequency of familial sarcoidosis is probably
      underestimated because of the big number of latent forms. A review of the
      literature allowed us to find 43 families with sarcoidosis. There is no clinical
      difference between familial sarcoidosis and usual forms of the disease, as
      confirmed by our findings. The preponderance of patients of the same sex in the
      same family, like our mother-daughter filiation is, described by the majority of
      the authors. This leads to suppose the existence of genetic factors. Neither this
      theory nor the one suggesting the possibility for etiologic agent that could
      perhaps affect the same persons in the same family can be currently demonstrated.
      Any association with an HLA group in the familial cases of sarcoidosis is
      unlikely. CONCLUSION: The rarity of familial sarcoidosis forms makes very
      difficult to establish theories regarding the familial predisposition.

PMID- 9775143
TI  - [Conn adenoma manifesting as reversible tetraparesis and rhabdomyolysis].
AB  - INTRODUCTION: Primary hyperaldosteronism is an uncommon cause of hypertension
      which classically features hypokaliemia, metabolic alkalosis and excessive
      urinary potassium excretion. Clinical manifestations of hypokalemia rarely reveal
      the diagnosis. EXEGESE: We report the case of a hypertensive patient who
      developed quadriparesis and rhabdomyolysis induced by a severe hypokalemia.
      Clinical manifestations were reversible after potassium supplementation.
      Laboratory and radiological findings led to the diagnosis of an aldosterone
      producing adenoma. Surgical treatment allowed correction of electrolyte
      abnormalities and improvement of hypertension. CONCLUSION: Although primary
      aldosteronism is rare, it should be systematically considered when arterial
      hypertension is associated with hypokalemia, even if the potassium depletion is
      due to diuretic therapy.

PMID- 9775144
TI  - [A peritoneal liquid mass].

PMID- 9775145
TI  - [Effectiveness of thalidomide treatment during cutaneous sarcoidosis].

PMID- 9775146
TI  - [Idiopathic hypereosinophilia syndrome and specific hepatitis. A case report].

PMID- 9775147
TI  - [What standpoint to take in regard to bacterial resistance to antibiotics in
      internal medicine].

PMID- 9775148
TI  - [Hyperthyroidism in people over 50 years of age in Senegal. Study of 31 cases
      observed over a 14-year period].
AB  - PURPOSE: Though common in elderly, with poor and masked symptomatology,
      hyperthyroidism has never been studied in people older than 50 years of age in
      African countries. METHODS: Of the 300 cases of hyperthyroidism that were
      observed during this study, 31 belonged to this category. We analyzed the
      frequency of various parameters, demographic characteristics, motivation for
      consulting, thyrotoxic syndrome, non thyrotoxic signs, cardiac manifestations,
      hormonal and scintigraphic characteristics, etiology and etiologic factors, and
      treatment. RESULTS: The frequency of hyperthyroidism in this population was 10%.
      Housewives were more numerous, with 20 cases observed in the 31 patients. The
      main group (13/31) was of rural origin. Signs that predominantly led to
      consultation were weight loss (23/31), cervical tumor (17/31), and palpitations
      (12/31). Three major signs were associated with the thyrotoxic syndrome: weight
      loss (29 cases), tachycardia (27/31), and the existence of tremors in the
      extremities (22/31). Hormone assays showed that thyroxine (T4) was about 265 +/-
      74 nmol/L and triiodothyronine (T3) about 6 +/- 2 nmol/L, at immunoradiometric
      assay; thyroid-stimulating hormone (TSH) was about 0.17 +/- 0.23 muIU/mL. Eye
      protrusion predominated in the nonthyrotoxic syndrome, with 25 cases in the 31
      patients. Etiologic forms of the disease were composed of 25 Grave's disease,
      with 22 typical cases. Etiologic factors were various, however without any case
      of neoplasia. Cardiac complications included two cases of atrial fibrillation. No
      iatrogenic form of the disease was observed. Mean initial carbimazole dosage was
      about 34 +/- 8 mg/d. Of the 23 patients, 15 had a favourable outcome.
      CONCLUSIONS: In this series, the high number of housewives and the patients'
      rural origin were less characteristic of hyperthyroidism than the Grave's disease
      etiology. This might be due to the young age of this African population.

PMID- 9775149
TI  - [Lymph node tuberculosis in France in non-immunosuppressed adults: current
      pathology].
AB  - PURPOSE: Lymph node tuberculosis is more frequent in Africa or in HIV-infected
      patients. METHODS: We review results that were obtained in 18 patients with lymph
      node tuberculosis but without infection by HIV. Eight French native patients
      (mean age: 69 years) and ten African patients (mean age: 32.5 years) were
      included into the study. RESULTS: Of the 18 patients, 14 had exclusively
      hematopoietic localizations, two with medullar involvement and two with either
      liver or spleen involvement. Normal erythrocyte sedimentation rate was found in
      two out of 18 cases and normal C-reactive protein levels in seven out of 17
      cases. Lymph node biopsy revealed lesions typically associated with tuberculosis
      in 12 out of 14 patients, two of them had no necrosis. Inflammatory syndrome was
      inconstant, tuberculin test sometimes negative. A favorable outcome was seen in
      all cases after 6, 12 or 18 months of treatment, depending on clinical
      appreciation. CONCLUSION: Tuberculous lymphadenopathy in non-HIV-infected
      patients may occur without inflammatory syndrome, with sometimes negative
      tuberculin test and without lymph node necrosis.

PMID- 9775150
TI  - [UV-induced immunosuppression and skin cancers].
AB  - INTRODUCTION: The increased incidence of skin cancers is due to modifications of
      our behavior toward solar exposure. Photocarcinogenesis represents the sum of
      complex and intricate events that lead to the occurrence of skin cancers. CURRENT
      KNOWLEDGE AND KEY POINTS: In epidermal cells UV light induces lesions of DNA that
      lead to modifications in oncogene and tumor suppressor gene expression. UV
      induced immunosuppression is also important for tumoral promotion. UV exposure
      decreases the number of Langerhans cells in the epidermis and modifies their
      antigen-presenting cell capacity. Numerous experimental data obtained in animal
      models clearly indicate the existence of a relationship between UV-induced immune
      suppression and skin cancers. In humans, growing evidence suggests that skin
      cancers and photoimmunosuppression are linked. FUTURE PROSPECTS AND PROJECTS:
      Better knowledge of mechanisms involved in UV-induced immune suppression is
      essential for developing new strategies aimed at photoprotection and cancer
      prevention.

PMID- 9775151
TI  - [New macrolides].
AB  - INTRODUCTION: Following their use for a few years, the place of new macrolides
      can be assessed. CURRENT KNOWLEDGE AND KEY POINTS: "New macrolides", ie,
      roxithromycin, clarithromycin, azithromycin and dirithromycin, are derivated from
      erythromycin and defined by different pharmacokinetic parameters: longer half
      time with better oral administration and shorter duration of treatment, better
      tissue concentrations with reduction of dosages and better tolerance, high
      cellular concentration with good activity. However, new macrolides and
      erythromycin do not show major differences in their antibacterial spectrum
      against usual pyogenic strains. Clinical use of new macrolides extends to
      opportunistic infections, such as atypical mycobacterial infections or
      toxoplasmosis, occurring in the course of HIV infection. New macrolides are also
      recommended for the treatment of Helicobacter pylori-related gastroduodenal
      ulcer. FUTURE PROSPECTS AND PROJECTS: New macrolides have opened new avenues in
      the development of anti-infectious strategies. Due to their good efficacy against
      Chlamydia pneumoniae which is suspected of inducing vascular diseases, the
      upcoming use of ketolids and the development of their non-antibiotic effects, the
      future of macrolides is favorable.

PMID- 9775152
TI  - [Acute alveolitis after using a waterproofing aerosol: apropos of 2 cases].
AB  - INTRODUCTION: Waterproofing sprays for leather clothing have seldom been involved
      in severe accidents. In some circumstances, their pulmonary toxicity is marked,
      as shown by two case reports and a review of the literature. EXEGESIS: Acute
      alveolitis is described in two young adults without previous respiratory illness,
      following the use of a waterproofing spray for leather clothing. Clinical
      features typical of a flu-like reaction (malaise, fever and chills) were
      associated with dyspnea and with hemoptysis in one patient. X-ray examination
      evidenced lesional edema which quickly resolved after symptomatic treatment. The
      toxic mechanism is debated, but experimental data and clinical findings suggest
      the causative role of recently introduced fluoropolymers. CONCLUSIONS:
      Waterproofing sprays for leather clothing may induce severe respiratory illness
      after massive inhalation in confined area. Treatment is supportive.

PMID- 9775153
TI  - [Cardiac manifestations of polymyositis. Apropos of 2 Senegalese cases].
AB  - INTRODUCTION: Polymyositis cardiac involvement varies between 37% and 70%.
      EXEGENESIS: The authors report two cases of polymyositis with myocardial
      involvement observed in Senegal; the first case is a cardiac failure revealing an
      acute polymyositis occurring in a 44-year-old woman; the second case is a 34-year
      old woman who had polymyositis with tachycardia and dyspnea: in the two cases
      echocardiography showed a left ventricular concentric hypertrophy with preserved
      systolic function and altered diastolic function; clinical and echocardiographic
      resolution were obtained by corticosteroid medication. CONCLUSION: Myocardial
      localization is the most common polymyositis cardiac involvement; clinical
      symptomatology is rare (3.3% to 6%). sometimes revealing polymyositis;
      electrocardiographic abnormalities are found in 18% to 81% cases and echographic
      abnormality in 42% cases; cardiac involvement is of bad prognosis.

PMID- 9775154
TI  - [Brain stem metastasis revealing bronchopulmonary cancer: 2 cases].
AB  - INTRODUCTION: Brainstem metastasis is a very rare revealing feature of lung
      carcinoma. EXEGESIS: We report two cases of brainstem metastasis revealing lung
      carcinoma. In the first case, diagnosis was made on stereotaxic biopsy. In the
      second, the biopsy was not necessary as lung lesion was observed on thoracic CT
      scan. Diagnosis of metastasis is difficult when a brainstem tumor occurs.
      CONCLUSION: Stereotaxic biopsy is an interesting tool to distinguish between
      primary lesion and metastasis, but only when diagnosis work-up of primary cancer
      is negative.

PMID- 9775155
TI  - [IgM kappa lymphoma with antisulfatide antibodies revealed by cervical motor
      neuropathy simulating amyotrophic lateral sclerosis].
AB  - INTRODUCTION: It is well known that polyneuropathy is associated with monoclonal
      IgM kappa. EXEGESIS: We report the case of a 79-year-old man with lymphoma and
      motor neuron disease at cervical level simulating amyotrophic lateral sclerosis
      (ALS). Neurological deficit with inflammatory process evolved within 4 months.
      Electrophysiological findings showed increased and enlarged muscular potentials
      with neurogenic patterns. Nerve conduction velocities were normal, with neither
      multifocal neuropathy nor persistent conduction blocks. Besides mixed
      cryoglobulinemia type II, antisulfatide antibodies issued from monoclonal IgM
      were found. They were directed against myelin glycosphingolipids. No
      antiganglioside GM1 antibodies could be detected. This not only evoked ALS but
      also proximal motor axonopathy related with monoclonal IgM. CONCLUSIONS: This
      case suggests that antisulfatide antibodies often present in sensitive
      demyelinating polyneuropathy could also be involved in lower motor neuron
      syndrome.

PMID- 9775157
TI  - [Resistant high back pain].

PMID- 9775156
TI  - [Growth hormone: a magical potion?].
AB  - INTRODUCTION: The various components of the growth hormone (GH)-insulin-like
      growth factor (IGF-I) axis and their binding proteins have many peripheral
      effects, mainly on bone, growth, activation of main cellular functions, energy
      metabolism and protein anabolism. They contribute to adapt an individual to
      circumstances of life and illness. CURRENT KNOWLEDGE AND KEY POINTS: The
      unlimited supply of recombinant GH makes it possible to treat not only children
      with short stature but other disorders. In adults with GH deficiency, it has a
      marked effect on subjective well-being and body composition, and improves
      physical activity. GH may be promoted in new therapeutic areas such as severe
      hypercatabolic and denutrition states, dilated cardiomyopathy and several other
      more hypothetical areas. GH is not a wonder drug increasing physical performances
      in sport competitors or fighting against senescence. FUTURE PROSPECTS AND
      PROJECTS: GH is a new therapeutic tool. Its efficacy must be evaluated through
      double-blind, placebo-controlled clinical trials. Currently, only benefits on
      psychological and physical symptoms of GH deficiency in adults have been
      validated.

PMID- 9775158
TI  - [Perimesencephalic hemorrhage and intake of norpseudoephedrine].

PMID- 9775159
TI  - [Exudative gastroenteropathy revealing primary CMV infection in an
      immunocompetent adult].

PMID- 9775160
TI  - [Pneumococcal peritonitis of gynecologic etiology].

PMID- 9775161
TI  - [Prostatic localization of periarteritis nodosa. Apropos of a case].

PMID- 9775162
TI  - [Rifampicin-glucocorticoid combinations].

PMID- 9775163
TI  - [Sarcoidosis and pregnancy. A retrospective study of 11 cases].
AB  - PURPOSE: To analyze the evolutive profile of sarcoidosis together with reciprocal
      interactions between pregnancy and sarcoidosis. METHODS: All events that occurred
      during pregnancy in 11 women presenting with sarcoidosis were analyzed.
      Histological confirmation was obtained for the 11 cases. For all pregnancies were
      analyzed the course of both sarcoidosis and pregnancy, and the influence of
      pregnancy on the disease evolution. RESULTS: Among 33 pregnancies, 23 led to the
      birth of healthy fetuses (five spontaneous abortions, four voluntary abortions,
      and one therapeutic abortion). The major event was fetal hypotrophy in six cases.
      Three of them occurred during pregnancy in prednisone-treated patients with
      active sarcoidosis. No relapse of cured sarcoidosis or further evolution of
      sarcoidosis that was inactivated as of the beginning of pregnancy were observed.
      The course of active sarcoidosis varied, as improvement (one case), worsening
      (two cases) and stabilization (two cases) were observed. During the first year of
      follow-up after delivery, four relapses and, in two cases, preliminary signs of
      the disease were observed. CONCLUSION: Apart from the hypothetical but not
      definite risk of hypotrophy, no negative interaction between sarcoidosis and
      pregnancy could be established. Pregnancy does not seem to interfere with the
      course of sarcoidosis. Considering the risk of relapse after delivery, pregnant
      women presenting with sarcoidosis should benefit from clinical and radiological
      follow-up.

PMID- 9775164
TI  - [Epidemiologic characteristics of cerebral toxoplasmosis in 399 HIV-infected
      patients followed between 1983 and 1994].
AB  - OBJECTIVE: To describe the epidemiological characteristics of toxoplasmic
      encephalitis in HIV-infected patients with a more than 12-year follow-up.
      METHODS: From a data base of 1,628 AIDS subjects hospitalized from 1983 to 1994,
      we studied the epidemiological characteristics of 399 patients with toxoplasmic
      encephalitis. Diagnosis of toxoplasmic encephalitis was based on the association
      of central neurological disorders, typical lesions on CT scan or MRI, and
      favorable outcome under appropriate toxoplasmosis therapy. RESULTS: Four hundred
      sixty-four cases of toxoplasmic encephalitis were reported in 399 patients (24.5%
      of the patients with AIDS). The overall incidence was 20.5 per 100 patients-year.
      Toxoplasmic encephalitis was the first AIDS defining event in 51% of the cases
      and revealed HIV infection in 13% of the cases. In the remaining 49%, the mean
      delay from AIDS diagnosis to toxoplasmic encephalitis was 13 months (range: 1-71
      months). At the time of diagnosis, mean CD4 count was 44/mm3 (range: 0-408/mm3).
      Antibodies to Toxoplasma gondii were found in 97% of the cases. Before the first
      episode of toxoplasmic encephalitis, 58% of the patients were given
      antiretroviral therapy (mean: 17.8 months; range: 1-64 months). Of the 399
      patients with toxoplasmic encephalitis, 366 (92%) did not receive any primary
      toxoplasmosis prophylaxis. Among them, 205 (56%) did not receive any drug
      prophylaxis, and 161 (44%) had Pneumocystis carinii pneumonia prophylaxis alone
      (aerosolized pentamidine). Thirty-three failures were observed (8%) with
      cotrimoxazole: 14 cases (3%) were considered to have irregular compliance. Sixty
      five relapses were observed in 52 patients. At the end of the study 334 patients
      had died (84%). The median survival was 11.4 months (95% confidence interval,
      range: 10.4-12.4 months). CONCLUSIONS: Toxoplasmic encephalitis incidence has
      decreased since the introduction of appropriate drug prophylaxis.

PMID- 9775166
TI  - [Epilepsy and cancer].
AB  - INTRODUCTION: Seizures are common in patients presenting with intracranial
      tumors. Nevertheless, the incidence of cancer is not higher in patients with
      seizures. We attempted to summarize situations that can lead to the diagnosis or
      treatment of seizures in patients presenting with cancer. CURRENT KNOWLEDGE AND
      KEY POINTS: Focal neurological signs on clinical examination when seizures occur
      for the first time in patients with cancer lead to brain imaging. As a result of
      recent advances in neuro-imaging techniques, the presence of a tumor is now more
      frequently observed in patients with seizures. PERSPECTIVES AND FUTURE PROJECTS:
      As it may have irritating effects on the cerebral cortex, chemotherapy is able to
      either increase or induce seizures in patients presenting with cancer. Potential
      pharmacological interactions between antiepileptic and cytotoxic drugs thus
      require close surveillance in patients with cancer.

PMID- 9775165
TI  - [Gougerot-Sjogren syndrome and malignant lymphoproliferative syndromes].
AB  - INTRODUCTION: This review is aimed at defining the frequency, anatomical and
      clinical presentation, pathogenesis, predictive factors and treatment of
      malignant lymphoproliferative diseases occurring in the course of Sjogren's
      syndrome. CURRENT KNOWLEDGE AND KEY POINTS: The frequency of non-Hodgkin's
      lymphoma (NHL) is estimated to be about 7%. Other malignant lymphoproliferative
      diseases (Waldenstrom's macroglobulinemia, multiple myeloma, Hodgkin's disease)
      are rarely observed. NHL is most frequently extranodal (affecting the salivary
      glands, stomach, lung, etc) in low grade malignancy (MALT lymphoma [mucosa
      associated lymphoid tissue]). The pathogenesis of NHL in Sjogren's syndrome is a
      multi-step process, including B cell monoclonal proliferation, oncogenic and/or
      infectious agents, and/or cytokines. Various predictive factors such as
      persistent enlargment of parotid glands, adenopathy, splenomegaly, mixed
      cryoglobulinemia, monoclonal gammopathy, suggest potential lymphoma evolution.
      The treatment of Sjogren's syndrome-associated NHL depends on the type of
      lymphoma. Moreover, in patients with low-grade lymphoma therapeutical strategies
      varies according to the stage and evolution of the disease. FUTURE PROSPECTS AND
      PROJECTS: Future prospective longitudinal studies should permit to define the
      best criteria for malignant transformation and to improve therapeutical
      strategies.

PMID- 9775167
TI  - [Eosinophilic ascites and urticaria].
AB  - INTRODUCTION: The finding of eosinophilic ascites is unusual. It requires the
      search for the main etiology, i.e., parasitic or malignant disease, vasculitis or
      hypereosinophilic syndrome. The diagnosis of exclusion is either mucosal,
      muscular or serous eosinophilic gastroenteritis. This last type, the most unusual
      -as less than 50 cases have been documented until now--is associated with
      eosinophilic ascites. EXEGESIS: We report a new case of serous eosinophilic
      gastroenteritis that occurred in a 23-year-old woman. This case was unusual
      because of its clinical history, as abdominal pain fits (along with the
      occurrence of ascites) were associated with urticaria fits. The lack of
      eosinophils in both the blood counts and the various digestive biopsies were
      unusual too. The disease evolution was favorable with corticosteroid therapy;
      however, a minimal dose of 8 mg/day was necessary to control the disease
      symptoms. CONCLUSION: Because of its association with urticaria fits, this case
      emphasizes the need for differential diagnosis in patients with hypereosinophilic
      syndrome and food allergy.

PMID- 9775168
TI  - [Necrobiotic xanthogranulomatosis: a cutaneous manifestation of a monoclonal IgM
      gammopathy].
AB  - INTRODUCTION: Necrobiotic xanthogranulomatosis is a rare cutaneous disorder
      usually associated with monoclonal gammopathy. Most frequently, cutaneous lesions
      involve the face (periorbital region) and the trunk, and are characterized by
      indurated xanthomatous plaques and nodules. EXEGESIS: We describe a patient
      presenting with necrobiotic xanthogranulomatosis that was unusual, as it was
      associated with IgM kappa monoclonal gammopathy of undetermined clinical
      significance and because no periorbital involvement was observed. CONCLUSIONS:
      Necrobiotic xanthogranulomatosis should be distinguished from other cutaneous
      manifestations associated with plasma cell dyscrasias, such as normolipemic plane
      xanthoma. It can be associated with IgM gammopathy.

PMID- 9775169
TI  - [Occurrence of non-Hodgkin's lymphoma in chronic viral hepatitis C].
AB  - INTRODUCTION: We report the occurrence of non-Hodgkin's lymphoma during the
      course of chronic hepatitis C treated with alpha-interferon. EXEGESIS: Specific
      viruses such as Epstein-Barr virus and human T-cell leukemia viruses I and II may
      be at the origin of various lymphomas in human. The presence of B cell lymphoma
      in the course of chronic hepatitis C has already been described and could be
      related to the lymphoid tropism of hepatitis C virus. CONCLUSION: This new report
      of an association between chronic hepatitis C and B cell lymphoma should lead
      physicians to search for signs of lymphoma in patients with chronic hepatitis C.

PMID- 9775170
TI  - [Endobronchial tuberculosis presenting as an obstructive tumor in an HIV-1
      positive patient. Apropos of a case and review of the literature].
AB  - INTRODUCTION: A rare case report of endobronchial tuberculosis is reported in an
      HIV-1 positive patient of black African origin. EXEGESIS: A 38-year-old woman of
      Guinean origin, HIV-1 positive, presented with persistent right upper lobe
      opacity at chest X-ray. Computerized tomography of the chest after injection
      confirmed this finding and revealed right laterotracheal and Barety space
      adenopathy. Investigations of acid-fast bacilli in the biological media were
      negative. Fiberoptic bronchoscopy showed endobronchial lesion on the wall of the
      ventral part of the right upper lobe, which had the appearance of bronchogenic
      carcinoma, and infiltrates in the dorsal mucosa. Biopsy of the lesion revealed
      granuloma formation, but no evidence of caseation necrosis. Identification of
      Mycobacterium tuberculosis in sputum culture helped arrive at a diagnosis of
      endobronchial tuberculosis similar to obstructive bronchial tumor. CONCLUSION:
      This case of endobronchial tuberculosis is the first described in an HIV-1
      positive patient of black African origin. Mediastinal lymph node revealed by
      chest computerized tomography after injection could be the site of spreading of
      mycobacteria by fistulization of tuberculosis lymph node into the right main
      bronchus. Only the histology of lesions carried out during bronchial fibroscopy
      permitted the exclusion of endobronchial neoplasia. In addition, the sensitivity
      of direct microscopy for acid-fast bacilli is poor. Identification of
      Mycobacterium tuberculosis by sputum culture helped guide the diagnosis which was
      further confirmed by a good therapeutic response. This case of endobronchial
      tuberculosis in an immunodepressed patient underlines the difficulty in
      determining the etiology of pulmonary opacities.

PMID- 9775171
TI  - [Vitiligo in multiple autoimmune syndrome: a retrospective study of 11 cases and
      a review of the literature].
AB  - PURPOSE: The occurrence in the same patient of three or more autoimmune diseases
      defines multiple autoimmune disease. Multiple autoimmune disease is an unusual
      condition in which dermatological autoimmune diseases and especially vitiligo
      have an important place. METHODS: We examined retrospectively 11 cases of
      multiple autoimmune diseases associating vitiligo. We studied the clinical
      characteristics of vitiligo and those of the associated autoimmune disorders.
      RESULTS: Type III multiple autoimmune disease was diagnosed in all the 11 cases
      observed. Autoimmune vitiligo was the first autoimmune disorder observed in seven
      cases and was bilateral, symmetrical and acrofacial in eight cases. Autoimmune
      thyroid disorder was associated in ten cases. Our data confirms the important
      association between vitiligo and thyroid autoimmune disorders. CONCLUSION: The
      predominant female ratio and the acrofacial topography of skin lesions could
      predict association with others autoimmune disorders in patients with vitiligo.

PMID- 9775173
TI  - [An entity not to be ignored: focal nodular myositis].

PMID- 9775172
TI  - [Yellow nails].

PMID- 9775174
TI  - [Hyperalgesic malleolar ulcer: recovery on the withdrawal of hydroxyurea].

PMID- 9775175
TI  - [Hemophagocytic syndrome complicating seronegative rheumatoid polyarthritis: a
      differential diagnosis of Still's disease?].

PMID- 9775176
TI  - [Listeria monocytogenes: a rare cause of spontaneous bacterial peritonitis in
      liver cirrhosis].

PMID- 9775177
TI  - [Prolonged otorrhea: tuberculous otitis media].

PMID- 9775178
TI  - [Tyrosine kinase: implications in tumor pathology and therapeutic perspectives].
AB  - The tyrosine kinase family includes growth factor receptor and cytoplasmic
      enzymes. It plays a key role in normal cell division and abnormal cell
      proliferation and differentiation. The most common tyrosine kinases are the
      epidermal-growth factor (EGFR) and platelet-derived growth factor (PDGF)
      receptors, and a chromosome Philadelphia product, the Bcr-abl oncogene. Many
      studies have attempted to correlate clinical evolution of tumors with tyrosine
      kinase expression. However, clinical application of these new prognostic factors
      has not yet been demonstrated. More recently, tyrosine-phosphorylation inhibitors
      (tryphostin) have been developed in phase I studies. Results that were obtained
      show some objective responses in patients with glioblastoma and polymetastatic
      cancer. Another approach to block tyrosine kinase expression is the use of
      monoclonal antibodies. Trials using such antibodies have shown interesting
      preliminary results.

PMID- 9775179
TI  - [Loss of consciousness in the elderly].

PMID- 9775180
TI  - [Primary biliary cirrhosis and systemic scleroderma (Reynolds syndrome): apropos
      of 8 new cases. The contribution of accessory salivary gland biopsy].
AB  - PURPOSE: We report eight new cases of the association primary biliary cirrhosis-
      systemic sclerosis (Reynolds' syndrome) and study the contribution of labial
      salivary gland biopsy to the disease diagnosis. METHODS: We retrospectively
      collected clinical and biological data as well as results of labial salivary
      gland biopsies in eight patients with Reynolds' syndrome. RESULTS: The eight
      patients were female. Systemic sclerosis corresponded to a CREST syndrome in
      three patients, while in two other patients two features of the CREST syndrome
      were observed. Anticentromere antibodies were detected in these five cases. The
      last three patients had systemic sclerosis with bilateral pulmonary fibrosis in
      two cases. All patients presented with Sjogren's syndrome. Labial salivary gland
      biopsies performed in six patients showed in five cases an inflammatory
      infiltrate and focal sialadenitis typically associated with Sjogren's syndrome.
      In four cases, organic microangiopathy and fibrosis were suggestive of systemic
      sclerosis, and in four other cases, the presence of a pericanalicular infiltrate
      of lymphocytes and necrosis of the excretory ducts epithelial cells suggested the
      existence of primary biliary cirrhosis. In three patients, all histological
      lesions were found in the same labial salivary gland biopsy. CONCLUSION:
      Coexistence of histological lesions on the same labial salivary gland suggestive
      of primary biliary cirrhosis, systemic sclerosis and Sjogren's syndrome has never
      been described previously. The diagnostic value of labial salivary gland biopsy
      has to be assessed in this context.

PMID- 9775181
TI  - [Deep venous thrombosis of the upper limbs. Apropos of 49 cases].
AB  - PURPOSE: Upper-extremity thrombosis appears to be more frequent today, comprising
      about 2% of all deep venous limb thrombosis. Its severity depends on the type of
      possible complications, i.e., pulmonary embolism and post-thrombotic sequelae. In
      this retrospective series, we investigated both the predisposing factors and the
      evolution of upper-extremity deep venous thrombosis. METHODS: Forty-nine
      consecutive patients (24 men and 25 women, mean age 50.2 years) with upper
      extremity deep venous thrombosis documented by color Doppler ultrasonography (n =
      47) or phlebography (n = 2) were included in the study. RESULTS: Clinical
      manifestations were mainly pain (81.6%) and edema (93.9%). Mean time between the
      onset of clinical signs and diagnosis was 7.2 days. Thrombosis involved humeral
      (26.5%), axillary (46.9%), subclavian (73.5%) and jugular (24.5%) veins.
      Causative factors were malignancies (32.7%), venous catheters (22.4%), deep
      venous thrombosis related to effort or thoracic outlet syndrome (22.5%) and
      thrombophilic states (8.2%). During the 6-month follow-up, six patients developed
      symptomatic pulmonary embolism (12.2%); one recurrence (2.2%) and 19 post
      thrombotic sequelae such as residual edema (36.7%) were also observed. Initial
      therapy included heparin administration, principally subcutaneous low molecular
      weight heparins (n = 36/49). CONCLUSION: This series highlights the fact that
      upper-extremity deep venous thrombosis is mainly secondary to either malignancies
      or catheterization. Moreover, it confirms that color Doppler ultrasonography may
      be useful in the diagnosis of the disease and also underlines the high frequency
      of severe complications, i.e., pulmonary embolism and post-thrombotic sequelae.
      Finally, this study also demonstrates that low molecular weight heparins should
      be considered as the initial treatment of choice.

PMID- 9775182
TI  - [Sarcoidosis of the central nervous system].
AB  - PURPOSE: Current knowledge on central nervous system sarcoidosis. CURRENT
      KNOWLEDGE AND KEY POINTS: Sarcoidosis is localized in the central nervous system
      in 5 to 16% of the cases. Various neurological manifestations are observed,
      including: seizures, cognitive or psychic manifestations, hypothalamic and
      pituitary involvement, local pseudotumors, and hydrocephalus very frequently
      associated with asymptomatic lymphocytic meningitis and with cranial nerve palsy,
      particularly palsy of the seventh nerve, occurring less regularly. CNS
      localization is most often an early manifestation of the disease, unmasking
      sarcoidosis. It is often part of primary or secondary systemic polyvisceral
      sarcoidosis. The diagnosis is mainly based on two arguments: confirmation of the
      existence of systemic sarcoidosis and clinical and paraclinical compatibility of
      neurological abnormalities (particularly at magnetic resonance imaging [MRI]).
      Neurological histopathology is rarely necessary to confirm the diagnosis.
      Corticotherapy is indicated in all symptomatic cases and most often leads to a
      more or less complete clinical response evidenced by regression of active lesions
      identified on MRI. The treatment must often be prolonged for several years, and
      clinical and MRI evolution help guide therapeutical choices for dosages and
      threshold doses. CNS involvement is potentially severe with mortality and
      morbidity rates that are not insignificant. Limiting of iatrogenic risks requires
      adequate follow-up. PERSPECTIVES AND PROJECTS: Multicenter studies are necessary
      to determine factors influencing the incidence and long-term prognosis of CNS
      sarcoidosis treated with corticotherapy. The efficacy of treatments other than
      corticotherapy must be evaluated.

PMID- 9775183
TI  - [Angiitis of the central nervous system in systemic diseases].
AB  - PURPOSE: This review is aimed at presenting classification and diagnosis criteria
      of isolated central nervous system (CNS) angiitis, and at proposing guidelines
      for diagnosis and management of this disease. CURRENT KNOWLEDGE AND KEY POINTS:
      Isolated CNS angiitis are rare and most information has been provided by studies
      of very small series. Angiitis can be primitive or secondary to infectious,
      neoplastic diseases, or toxics. Clinical manifestations and radiologic
      abnormalities are not specific. A brain biopsy is therefore often required to
      confirm the diagnosis, as numerous non-inflammatory vascular diseases can mimic
      both clinically and radiologically isolated CNS angiitis. PERSPECTIVES AND
      PROJECTS: To help guide the diagnosis and therapeutical management of patients
      with CNS angiitis, strict classification criteria should be used: 1) rule out the
      various diseases that can mimic clinical and radiological CNS aspects related to
      isolated angiitis and differentiate "isolated CNS angiitis" from "CNS angiitis
      associated with systemic diseases"; 2) search for factors associated with the
      development of a "secondary CNS angiitis"; 3) check presumed mechanism at the
      origin of the cerebral vascular disease: "angiitis" versus "angiopathy"; 4) if
      the diagnosis of "primary CNS angiitis" is still suspected, it seems reasonable
      to perform cerebral and leptomeningeal biopsies. Treatment is still unknown and
      has to be discussed on a case by case basis according to the severity and
      progression of symptoms.

PMID- 9775184
TI  - [Malignant peritoneal mesothelioma occurring in periodic disease: apropos of a
      case].
AB  - INTRODUCTION: Peritoneal mesothelioma is a rare malignant neoplasm that might be
      linked to chronic peritoneal inflammation. As well, the association peritoneal
      mesothelioma-familial Mediterranean fever is uncommon. EXEGESIS: We report the
      case of a 60-year-old man who presented for 30 years with standard periodic
      familial Mediterranean fever accompanied by acute abdominal episodes, sensitive
      to colchicine. Between 1988 and 1995, acute abdominal episodes were accompanied
      by more and more profuse recurrent ascites, partially resolving under colchicine
      treatment. In 1995, the last episode was severe (with loss of weight and
      inability to tolerate feeding) and conducted to the patient's death due to
      peritoneal mesothelioma, as confirmed by the biopsy. CONCLUSION: Profuse and
      recurrent ascites is unusual in standard periodic familial Mediterranean fever.
      Asbestos exposure at the origin of peritoneal mesothelioma is not well
      documented. Furthermore, the disease clinical and paraclinical features are
      misleading, and the diagnosis is based on histology. The prognosis is severe, and
      treatment is usually disappointing. Our observation clearly demonstrates the
      interconnection between an unusual form of profuse and relapsing ascites that
      occurred in the course of a periodic disease and peritoneal mesothelioma. The
      potential role of recurrent peritonitis related to familial Mediterranean fever
      in the pathogenesis of the tumor is discussed.

PMID- 9775185
TI  - [Geotrichum capitatum infection in a neutropenic patient. Apropos of a case and
      review of the literature].
AB  - INTRODUCTION: Geotrichum capitatum sepsis are rare, occurring exclusively in
      immunocompromised patients. EXEGESIS: We report the case of a patient with acute
      leukemia, presenting with chemotherapy-induced neutropenia and hospitalized in an
      intensive care unit for a severe sepsis. In spite of an antibiotic and antifungal
      treatment, the patient died of cardiorespiratory failure. Later on, blood
      cultures proved to be positive for Geotrichum capitatum. CONCLUSION: If fungal
      infections are common in neutropenic patients, Geotrichum capitatum sepsis remain
      exceptional. The portal of entry is digestive or respiratory, and the invasion is
      favored by immunodepression and suppression of the normal microbial flora.
      Induced lesions can be multiorganic. The treatment is not well established, and
      the association of either amphotericine B and 5-fluorocytosine or amphotericine B
      and itraconazole would lead to better results. Nevertheless, the prognosis is
      still unfavorable, with a mortality rate of approximately 75%.

PMID- 9775186
TI  - [A rare cause of intra-alveolar hemorrhage: a transfusion-related incident with
      leukoagglutination due to antigranulocyte antibodies (Trali syndrome)].
AB  - INTRODUCTION: Transfusion-related acute lung injury (TRALI) is an infrequent but
      life-threatening complication of hemotherapy, usually secondary to passive
      transfer of antibody from the donor's plasma to the recipient. TRALI is a
      diagnosis of exclusion often masked by underlying factors. EXEGESIS: We report a
      new case of TRALI in a patient with severe multinevritis associated with
      Sjogren's syndrome and cryoglobulinemia, who had received intravenous
      immunoglobulins. CONCLUSION: This case report underlines the difficulty to
      establish a diagnosis in both acute respiratory failure and intra-alveolar
      hemorrhage in patients with auto-immune disorders. This case report also
      emphasizes the necessity of taking precautions in these immunocompromised
      patients in whom hemoglobin transfusion is required.

PMID- 9775187
TI  - [A metastatic neuroendocrine tumor with exceptional outcome!].
AB  - INTRODUCTION: Neuroendocrine tumors are rare, with poor prognosis when not or
      poorly differentiated. EXEGESIS: The authors report the case of a patient who
      presented with a metastatic poorly differentiated neuroendocrine tumor that was
      resistant to chemotherapy. The different sites of the carcinoma were lung,
      pancreas, kidney and lymph nodes. The patient received no treatment and complete
      spontaneous remission appeared after 21 months. This remission has been lasting
      for five years. CONCLUSION: It is the first case of spontaneous remission of a
      metastatic poorly differentiated neuroendocrine tumor. The evolution and
      classical sites of neuroendocrine tumors are reviewed. Renal metastasis is also
      unusual. This report illustrates the fact that neuroendocrine tumors are
      heterogeneous.

PMID- 9775188
TI  - [The practical value of the level of D-dimer in the exclusion diagnosis of venous
      thromboembolic disease].

PMID- 9775189
TI  - [Pulmonary opacities].

PMID- 9775190
TI  - [Fistulated sigmoid pseudodiverticulitis of tuberculous origin].

PMID- 9775192
TI  - [Early developing pancarditis and unclassified inflammatory rheumatism].

PMID- 9775191
TI  - [A new case of acute hepatitis type E in France].

PMID- 9775193
TI  - [Beware of the dog! A syndrome resembling thrombotic thrombocytopenic purpura
      associated with Capnocytophaga canimorsus septicemia].

PMID- 9775194
TI  - [Familial mediterranean fever is a hereditary disorder of the neutrophil].

PMID- 9775195
TI  - [Patients admitted to the intensive care unit for iatrogenic disease. Risk
      factors and consequences].
AB  - PURPOSE: Data pertaining to iatrogenic diseases have been recorded over the last
      25 years. Regarding the evolution of medical practice (general ageing, more and
      more powerful drugs and complex procedures), it is not known whether the
      incidence and the consequences of iatrogenic diseases have changed since their
      first evaluation. METHODS: To determine the admission rate to intensive care
      units for iatrogenic diseases, with the purpose of analyzing risk factors and
      consequences, and to compare our results with previous data recorded in 1979
      (admission rate: 12.6%, mortality: 20%, preventable events: 47%), a 1-year
      retrospective study was conducted in an intensive care unit (ICU). RESULTS:
      During 1994, 68 (10.9%) out of 623 patients were admitted to the ICU for
      iatrogenic diseases (drugs: 41, medical acts: 12, surgical acts: 15). They were
      not different--in terms of severity, mortality, workload and length of stay in
      the ICU--from the other 555 patients hospitalized for other reasons. They were
      hospitalized on average for 472 days in the ICU, with a 13% fatality rate and a
      financial cost of US $688,470. Risk factors for iatrogenic diseases were the age
      and the number of prescribed drugs. The rate of preventable events was 51%.
      CONCLUSIONS: In this study, the occurrence of life-threatening iatrogenic
      diseases was a persistent and important purpose for admission to the ICU. Risk
      factors and consequences are still identical to those reported in 1979. Our
      results emphasize the persistence of the noxious impact of iatrogenic diseases on
      the quality and cost of medical care.

PMID- 9775196
TI  - [Aetiologic features of osteoporosis in male patients aged less than 50 years:
      study of 28 cases with a comparative series of 30 patients over the age of 50].
AB  - PURPOSE: To study the aetiologic factors of osteoporosis (OP) in young male
      patients, we conducted a retrospective study of male osteoporosis observed in our
      department during the past 20 years. METHODS: Patients included in the study were
      over 16 years of age and had a fracture or a decreased bone mineral density with
      a T score (assessed at the spine or at the spine and femoral neck) below -2.5 SD.
      The age and circumstances of diagnosis, serum and 24-hour urinary calcium and
      phosphorus investigations, hormonal measurements (including parathyroid hormone,
      thyroid hormones, cortisol and testosterone), bone biopsy and the final diagnosis
      were analyzed. RESULTS: One hundred and nineteen patients responded to the
      defined diagnosis criteria. Twenty-eight were less than 50 years of age (group I
      or young male osteoporosis). Data were compared with those of 30 patients more
      than 50 years of age (group II). In group I, an aetiology was found in 17 out of
      28 cases (60.7%) (secondary osteoporosis: OP II), while 11 out of 28 patients
      (39.3%) had primary or idiopathic osteoporosis (OP I). In group II, the frequency
      of OP I was 19 out of 30 cases (63.3%) and 11 out of 30 patients (36.6%) had OP
      II. However, the frequency of OP II did not differ significantly between the two
      groups (P = 0.11). The aetiology in group I was either hypogonadism (6 out of
      17), alcoholism (2 out of 17), mastocytosis (2 out of 17), primary biliary
      cirrhosis (1 out of 17), osteogenesis imperfecta (1 out of 17), idiopathic
      hypercalciuria (1 out of 17), corticosteroid treatment (1 out of 17) or
      ankylosing spondylitis (1 out of 17). Multiple causes were found in 5 out of 17
      cases. The causes of osteoporosis in group II included hypogonadism (2 out of
      11), alcoholism (2 out of 11), idiopathic hypercalciuria (2 out of 11),
      glucocorticosteroid therapy (6 out of 11) and rheumatoid arthritis (1 out of 11).
      CONCLUSIONS: Our results were compared to those of the various series reported in
      the literature which, though focusing on male osteoporosis, often included
      elderly patients. To determine whether osteoporosis in young male is more often
      OP II, further prospective studies are required.

PMID- 9775197
TI  - [Genetic diagnosis of periodic disease].
AB  - INTRODUCTION: Periodic disease is a hereditary disorder. Until recently its
      diagnosis was essentially based on clinical criteria. When the clinical picture
      was incomplete or atypical, it often required elimination of other diagnoses
      which sometimes involved extensive and useless investigations. Diagnosis was
      consequently delayed or irrelevant, with the risk of renal failure when the
      patient was not treated (or tardily treated). CURRENT KNOWLEDGE AND KEY POINTS:
      Efforts of molecular geneticists have allowed to track and recently to identify
      the gene (MEFV) responsible for this disease. Today blood sampling enables
      identification of the causative mutations, sometimes even before the onset of
      symptoms. FUTURE PROSPECTS AND PROJECTS: Four mutations clustered on exon 10
      already account for 74% of cases in patients originating from the most affected
      populations and presenting with complete clinical picture. Identification of rare
      mutations should progressively allow improvement of the test sensitivity,
      especially in patients with a less typical form of the disease.

PMID- 9775198
TI  - [Prevention of glucocorticoid induced osteoporosis].
AB  - INTRODUCTION: It is generally accepted that moderate to high dose glucocorticoid
      therapy is associated with bone loss and increased fracture risk. The degree of
      bone loss is closely related to the cumulative corticosteroid dose and the
      highest rate of bone loss is observed in the first 3 to 6 months of therapy.
      CURRENT KNOWLEDGE AND KEY POINTS: Optimal management strategies to prevent bone
      loss should include the use of the lowest efficacious dose of glucocorticoid.
      Alternate day dosing and bolus do not provide effective protection. Prevention
      should basically include adequate calcium intakes and additional vitamin D. All
      patients should be encouraged to modify their lifestyles, including smoking
      cessation and limitation of alcohol consumption; physical exercise for 30 minutes
      to 1 hour every day should also be recommended. Sodium restriction and thiazide
      diuretics have been shown to improve hypercalciuria that sometimes accompanies
      glucocorticoid therapy. Hormone replacement therapy should be recommended in
      postmenopausal women, while estrogen-containing oral contraceptives should be
      advocated in young women with menstrual irregularities, except for patients with
      systemic lupus erythematosus. FUTURE PROSPECTS AND PROJECTS: Dual-energy X-ray
      absorptiometry may be useful in patient with high risk of glucocorticoid-induced
      osteoporosis, as it allows accurate measurements of bone mineral density.
      Etidronate recently proved to be efficacious in preventing bone loss and
      decreasing the number of vertebral fractures in menopausal women.

PMID- 9775199
TI  - [Chondrosarcoma in nasal fossae and Maffucci's syndrome].
AB  - INTRODUCTION: Maffucci's syndrome is a congenital non-hereditary disease very
      similar to Ollier's disease and associates multiple cutaneous hemangiomas,
      dyschondroplasia and often enchondromas. EXEGESIS: We report a unique case
      involving synchronous localization of chondrosarcoma in nasal fossae and anterior
      chest wall, disclosing Maffucci's syndrome. CONCLUSION: Atypical chondrosarcoma
      localization must lead to further investigation of potential multiple
      enchondromatosis.

PMID- 9775200
TI  - [Bronchopulmonary carcinosarcoma].
AB  - INTRODUCTION: Bronchopulmonary carcinosarcoma is an uncommon neoplasm consisting
      of mixed malignant epithelial and mesenchymal cells. EXEGESIS: We report a case
      of bronchopulmonary carcinosarcoma in a 62-year-old man illustrating some
      characteristics of this tumor of poor prognosis and unknown histogenesis.
      CONCLUSION: Bronchopulmonary carcinosarcoma has clinical and X rays features
      identical to those of bronchopulmonary epithelial malignant tumors. Most of the
      authors consider that a totipotential cell might be at the origin of this "mixed"
      tumor. Although 90% of bronchopulmonary carcinosarcomas are resectable, their
      prognosis is worse than that of other lung cancers, with a 6-month median
      survival.

PMID- 9775201
TI  - [Deep venous thrombosis in an adult with varicella].
AB  - INTRODUCTION: Some viral infections are associated with deep venous thrombosis.
      We report a case of deep venous thrombosis in an adult with varicella. He had
      neither known predisposing factors for thrombosis nor thrombophilia. EXEGESIS:
      Transient significant level of antiphospholipid antibodies and lupus circulating
      anticoagulant were observed. There was no evidence of thrombophilia. Deep venous
      thrombosis has been mostly associated with varicella in children. A transient
      protein S deficiency was present in almost all cases, though it was sometimes
      related to an anti-protein S antibody. This association is exceptional in adults.
      Some viruses such as herpesvirus and HIV are responsible for endothelium
      dysfunction, but this is still unclear in the case of varicella-zoster virus.
      CONCLUSION: In our observation, endothelium activation or antiphospholipid
      antibodies might be responsible for thrombosis.

PMID- 9775202
TI  - [Association of pulmonary artery aneurysm, right heart thromboses and
      antiphospholipid antibodies in Behcet's disease].
AB  - INTRODUCTION: Cardiac thromboses are unusual in the course of Behcet's disease
      and are frequently associated with endomyocardial fibrosis of the right heart.
      Vascular pulmonary involvement with either pulmonary aneurysm or parenchyma
      alterations is also often observed. However, pathogenesis of thromboses occurring
      in the course of Behcet's disease is still unclear. CASE REPORT: The authors
      report the case of a 28-year-old man who presented with Behcet's disease
      accompanied by pulmonary aneurysm, multiple thrombi of the right heart and
      antiphospholipid antibodies. CONCLUSION: The choice of therapeutical strategies
      for curative treatment of this association as well as the interpretation of the
      role of antiphospholipid antibodies in this polyvascular disease raises
      questions.

PMID- 9775203
TI  - [Multiple hepatic tumors].

PMID- 9775204
TI  - [Erythroblastopenia secondary to zidovudine].

PMID- 9775205
TI  - [Hyponatremia and benazepril].

PMID- 9775206
TI  - [Heparin osteoporosis: a case report].

PMID- 9775207
TI  - [Periodic bursitis in the iliac psoas].

PMID- 9775208
TI  - The photoreceptor.

PMID- 9775209
TI  - The retinal pigment epithelium as a developmental regulator of the neural retina.
AB  - Melanin-related agents regulate the development of the mammalian neural retina,
      because in albinos there are a range of retinal deficits including abnormal
      connections between the eye and brain, an underdeveloped central retina and a rod
      deficit. These deficits may arise because gradients of retinal development in the
      albino are delayed and the retina is abnormally proliferative, but also goes
      through a subsequent period of excessive cell death. This may be caused by a
      reduction in ocular DOPA in albinos as this is in the synthetic pathway of
      melanin and is a known cell cycle regulator.

PMID- 9775210
TI  - Structure of rhodopsin.
AB  - Two-dimensional crystals of rhodopsin were studied to determine the arrangement
      of the transmembrane alpha helices. A combination of electron cryo-microscopy,
      image processing and electron crystallography was used to extract amplitudes and
      phases from images, and a three-dimensional map to a resolution of 7.5 A was
      calculated. Density peaks for all seven transmembrane helices were observed and
      the helix axes for all seven helices could be estimated. Near the intracellular
      side, which interacts with the G protein transducin, we observed three layers of
      helices arranged differently from bacteriorhodopsin. The arrangement opens up
      towards the extracellular side forming a cavity that serves as the binding pocket
      for the retinal. This cavity is closed towards the intracellular side by the long
      and highly tilted helix 3, and must be closed towards the extracellular side by
      the loop linking helices 4 and 5 that is linked by a disulphide bridge to the
      extracellular end of helix 3.

PMID- 9775211
TI  - Molecular basis of dark adaptation in rod photoreceptors.
AB  - Following exposure of the eye to an intense light that 'bleaches' a significant
      fraction of the rhodopsin, one's visual threshold is initially greatly elevated,
      and takes tens of minutes to recover to normal. The elevation of visual threshold
      arises from events occurring within the rod photoreceptors, and the underlying
      molecular basis of these events and of the rod's recovery is now becoming
      clearer. Results obtained by exposing isolated toad rods to hydroxylamine
      solution indicate that, following small bleaches, the primary intermediate
      causing elevation of visual threshold is metarhodopsin II, in its phosphorylated
      and arrestin-bound form. This product activates transduction with an efficacy
      about 100 times greater than that of opsin.

PMID- 9775212
TI  - Control of rhodopsin activity in vision.
AB  - Although rhodopsin's role in activating the phototransduction cascade is well
      known, the processes that deactivate rhodopsin, and thus the rest of the cascade,
      are less well understood. At least three proteins appear to play a role:
      rhodopsin kinase, arrestin and recoverin. Here we review recent physiological
      studies of the molecular mechanisms of rhodopsin deactivation. The approach was
      to monitor the light responses of individual mouse rods in which rhodopsin was
      altered or arrestin was deleted by transgenic techniques. Removal of rhodopsin's
      carboxy-terminal residues which contain phosphorylation sites implicated in
      deactivation, prolonged the flash response 20-fold and caused it to become highly
      variable. In rods that did not express arrestin the flash response recovered
      partially, but final recovery was slowed over 100-fold. These results are
      consistent with the notion that phosphorylation initiates rhodopsin deactivation
      and that arrestin binding completes the process. The stationary night blindness
      of Oguchi disease, associated with null mutations in the genes for arrestin or
      rhodopsin kinase, presumably results from impaired rhodopsin deactivation, like
      that revealed by the experiments on transgenic animals.

PMID- 9775213
TI  - Post-Golgi trafficking of rhodopsin in retinal photoreceptors.
AB  - Rod outer segment renewal in retinal rod photoreceptors is mediated by polarised
      sorting of rhodopsin, and its associated proteins and lipids, on post-Golgi
      vesicles that bud from the trans-Golgi network and fuse with the specialised
      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. The intracellular sorting machinery that regulates
      budding, targeting and fusion of rhodopsin carrier vesicles has been studied
      using multiple means including a newly developed cell-free assay that
      reconstitutes vesicle budding. These studies have revealed an essential role for
      small GTP-binding protein rab6, as well as the carboxyl-terminal domain of
      rhodopsin, in the formation of post-Golgi vesicles. In this report their role in
      post-Golgi trafficking of rhodopsin and the maintenance of photoreceptor cell
      polarity and health is discussed.

PMID- 9775214
TI  - The photoreceptor mosaic.
AB  - The organisation of the human photoreceptor mosaic reflects evolutionary
      strategies for optimising visual information under a wide range of stimulus
      conditions: (1) The rod population dominates (max. 170,000/mm2 at c. 30 degrees
      sup.) except for the central 2 degrees and along the ora serrata. (2) Density of
      cone inner/outer segments reaches up to 300,000 mm2 in the fovea. A bundle of c.
      300-500 foveolar cones are further distinguished by having their synaptic
      terminals located within the capillary-free zone. Radial displacement (> 350
      microns) of foveal cone terminals may result in the lesion of two sets of cone
      pathways by perifoveal laser treatment. Along the ora serrata peripheral cone
      density (c. 4000) rises within a small rim (1 degree) to up to 20,000, but may be
      considerably decreased by cystoid degenerations. For the L- and M-cone
      subpopulations ratios of 2:1 to 1:1 and random arrangement are suggested. (3)
      Blue-sensitive (S-) cones constitute a regular and independent submosaic of c. 7%
      across the periphery. An annular maximum (1000-5000/mm2) at c. 1 degree surrounds
      the foveola. There density decreases and irregular zones lacking S-cones result
      in tritan deficiencies.

PMID- 9775215
TI  - Evolution of colour vision in vertebrates.
AB  - The expression of five major families of visual pigments occurred early in
      vertebrae evolution, probably about 350-400 million years ago, before the
      separation of the major vertebrate classes. Phylogenetic analysis of opsin gene
      sequences suggests that the ancestral pigments were cone pigments, with rod
      pigments evolving last. Modern teleosts, reptiles and birds have genera that
      possess rods and four spectral classes of cone each representing one of the five
      visual pigment families. The complement of four spectrally distinct cone classes
      endows these species with the potential for tetrachromatic colour vision. In
      contrast, probably because of their nocturnal ancestry, mammals have rod
      dominated retinas with colour vision reduced to a basic dichromatic system
      subserved by only two spectral classes of cone. It is only within primates, about
      35 millions years ago, that mammals 're-evolved' a higher level of colour vision:
      trichromacy. This was achieved by a gene duplication within the longer-wave cone
      class to produce two spectrally distinct members of the same visual pigment
      family which, in conjunction with a short-wavelength pigment, provide the three
      spectral classes of cone necessary to subserve trichromacy.

PMID- 9775216
TI  - What is the function of the cone-rich rim of the retina?
AB  - Although there is good histological evidence for a rim of cones extending round
      the margin of the human retina at the ora serrata, the function of these cones is
      unknown, and indeed it is not known whether they are functional at all. Four
      possibilities are discussed here: (i) the cones of the ora serrata may alert us
      to sudden movements in the far peripheral field, (ii) their signal may be used in
      estimating optic flow during locomotion, (iii) they may integrate light scattered
      within the globe of the eye or passing through the sclera, for purposes of colour
      constancy, or (iv) they may drive circadian rhythms. We report two experiments
      designed to detect psychophysical correlates of the cone rim. Under the
      conditions we have used, neither flicker detection nor colour naming show, near
      the limit of vision, a discontinuity that would correspond to the cone-rich rim.

PMID- 9775217
TI  - The cone dystrophies.
AB  - The cone dystrophies are a heterogeneous group of inherited disorders that result
      in dysfunction of the cone photoreceptors and sometimes their post-receptoral
      pathways. The major clinical features of cone dystrophy are photophobia, reduced
      visual acuity and abnormal colour vision. Ganzfeld electroretinography shows
      reduced or absent cone responses. On the basis of their natural history, the cone
      dystrophies may be broadly divided into two groups: stationary and progressive
      cone dystrophies. The stationary cone dystrophies have received more attention,
      and subsequently our knowledge of their molecular genetic, psychophysical and
      clinical characteristics is better developed. Various methods of classification
      have been proposed for the progressive cone dystrophies, but none is entirely
      satisfactory, largely because the underlying disease mechanisms are poorly
      understood. Multidisciplinary studies involving clinical assessment, molecular
      genetics, electrophysiology and psychophysics should lead to an improved
      understanding of the pathogenesis of these disorders.

PMID- 9775218
TI  - Animal models of human retinal dystrophies.
AB  - Naturally occurring retinal dystrophies in laboratory and companion animals
      represent a wealth of different conditions, some of which are important from a
      comparative point of view, and all of which offer opportunities to further the
      understanding of retinal function and reaction in health and disease. The study
      of animal models of retinal dystrophies has provided candidate genes for
      investigation in conditions of man such as retinitis pigmentosa and has also led
      to the identification of new genes and even new families of genes. Mutations in
      the gene for the beta subunit of cyclic GMP phosphodiesterase cause retinal
      dystrophies in man, mice and dog, and mutations in the gene for the structural
      protein peripherin/RDS result in a retinal dystrophy in the mouse and a spectrum
      of differing retinal dystrophies in man. Animals with homologous retinal
      dystrophies to man may make useful models for investigation of treatment either
      by drugs or by gene therapy. Furthermore the use of transgenics and gene
      targeting in laboratory mice offers the opportunity to create new models of human
      retinal dystrophies and also to investigate the effect of gene dysfunction.

PMID- 9775219
TI  - Molecular genetics of human retinal dystrophies.
AB  - Retinal dystrophies are a heterogeneous group of diseases in which the retina
      degenerates, leading to either partial or complete blindness. The severe and
      clearly hereditary forms, retinitis pigmentosa (RP) and various macular
      degenerations, affect approximately 1 in 3000 people, but many more suffer from
      aging macular dystrophy in later life. Patients with RP present with narrowing
      visual fields and night blindness, while those with diseases of the macula lose
      central vision first. Even before the advent of molecular genetics it was evident
      that these were heterogeneous disorders, with wide variation in severity, mode of
      inheritance and phenotype. However, with the widespread application of linkage
      analysis and mutation detection techniques, a complex underlying pathology has
      now been revealed. In total, 66 distinct non-overlapping genes or gene loci have
      been implicated in the various forms of retinal dystrophy, with more being
      reported regularly in the literature. Within the category of non-syndromic RP
      alone there are at least 22 genes (and probably many more) involved, with further
      allelic heterogeneity arising from different mutations in the same gene. This
      complexity presents a problem for those involved in counselling patients, and
      also compounds the search for therapies. Nevertheless, several lines of research
      raise the hope of generic treatments applicable to all such patients, while the
      greater understanding of normal visual function that arises from genetic studies
      may open up new avenues for therapy.

PMID- 9775220
TI  - The dystrophic retina in multisystem disorders: the electroretinogram in neuronal
      ceroid lipofuscinoses.
AB  - The neuronal ceroid lipofuscinoses (NCL) are neurodegenerative disorders with
      psychomotor deterioration, seizures, visual failure and premature death, all
      associated with abnormal storage of lipoproteins within lysosomes. The most
      common forms of NCL are an infantile form (INCL, CLN1), a late infantile form
      (LINCL, CLN2) and a juvenile onset form (JNCL, CLN3). The electroretinogram (ERG)
      is abnormal early in all three of these forms and eventually is totally ablated.
      The purpose of this report is to describe the ERG in INCL, LINCL and JNCL. The
      ERGs of 7 patients who were examined by the author over the past 15 years were
      reviewed. Ganzfeld ERG responses were recorded using the ISCEV standard protocol
      and an intensity response series over a 3.7 log unit range. The earliest ERG
      manifestation of INCL is a marked loss of the scotopic and photopic b-wave with
      relative preservation of the a-wave; this defect, which was evident for both rods
      and cones, suggests preservation of photoreceptor outer segment function with
      severe disturbance of transmission of the signal to the second-order neuron, the
      bipolar cells. For LINCL, the rod responses were mildly abnormal but more
      preserved than in INCL or JNCL. The cone b-wave amplitudes in patients with early
      LINCL were severely subnormal with prolonged implicit times. Patients with JNCL
      invariably showed severe to profound ERG abnormalities when first tested, with
      essentially no rod-mediated activity and marked loss of a-wave amplitudes with
      even greater loss of b-wave amplitudes, creating electronegative configuration
      waveforms. Differences in the ERG responses were thus found that provide further
      clues to the earliest site of pathology within the retina.

PMID- 9775221
TI  - Photoreceptor rescue.
AB  - Photoreceptor cell death is the final, irreversible event in many blinding
      diseases including retinitis pigmentosa, age-related macular disease and retinal
      detachment. This paper examines the potential strategies for preventing
      photoreceptor cell death in the context of current understanding of the
      mechanisms of cell death. There is evidence to suggest that photoreceptor cells
      are inherently vulnerable, apoptosis is the final common pathway of photoreceptor
      cell loss, and other retinal cells play an important role in the survival of rods
      and cones. Furthermore, the rationale of using neurotrophic factors as
      therapeutic agents in retinal degeneration is discussed in detail. Photoreceptor
      rescue by manipulation of genes involved in apoptosis and some pharmacological
      agents is also described.

PMID- 9775222
TI  - Retinal degeneration and transplantation in the Royal College of Surgeons rat.
AB  - The Royal College of Surgeons rat provides a valuable animal model for examining
      the ontogeny of inherited or acquired photoreceptor degeneration and for
      assessing various treatment paradigms. Here we describe a sequence of events in
      which photoreceptor loss induces secondary changes that ultimately result in a
      progressive loss of retinal ganglion cells. The functional consequences of
      photoreceptor loss are described and compared with those observed in dystrophic
      animals that received grafts of pigment epithelial cells at an early stage in the
      degenerative process. The results of this work suggest that transplantation might
      slow or halt the progress of photoreceptor loss in certain human retinal
      degenerative conditions, provided suitable safeguards have been put in place.

PMID- 9775223
TI  - Artificial vision.
AB  - Outer retinal degenerations such as retinitis pigmentosa (RP) and age-related
      macular degeneration (AMD) lead to blindness because of photoreceptor
      degeneration. To test whether controlled electrical stimulation of the remaining
      retinal neurons could provide form vision, we electrically stimulated the inner
      retinal surface with micro-electrodes inserted through the sclera/eye wall of 14
      of these patients (12 RP and 2 AMD). This procedure was performed in the
      operating room under local anaesthesia and all responses were recorded via a
      video camera mounted on the surgical microscope. Electrical stimulation of the
      inner retinal surface elicited visual perception of a spot of light (phosphene)
      in all subjects. This perception was retinotopically correct in 13 of 14
      patients. In a resolution test in a subject with no light perception, the patient
      could resolve phosphenes at 1.75 degrees centre-to-centre distance (i.e. visual
      acuity compatible with mobility; Snellen visual acuity of 4/200).

PMID- 9775224
TI  - Advances in confocal microscopy of the cornea.

PMID- 9775225
TI  - The infrastructure of the anterior chamber.

PMID- 9775226
TI  - Investigations for patients undergoing lacrimal surgery.

PMID- 9775227
TI  - Keratocyte density and size in conscious humans by digital image analysis of
      confocal images.
AB  - PURPOSE: Confocal microscopy can give images of high magnification and resolution
      in undisturbed living tissue. It provides new information about the cellular
      structure of the cornea. Our aim was to measure the density, size and
      distribution of keratocytes. METHODS: Healthy cornea in four subjects was
      examined using tandem scanning confocal microscopy. Methods for digital analysis
      of images were developed. RESULTS: Keratocyte density in confocal cross-sections
      was greatest immediately under Bowman's membrane (maximum 800 cells/mm2) and
      decreased sharply towards posterior cornea (minimum 65 cells/mm2). Cross
      sectional cell size ranged from 78 to 211 microns2, but did not correlate with
      depth in the tissue. CONCLUSIONS: Results are consistent with those of earlier
      work using histological and biochemical techniques in isolated tissue. The
      methods we have developed enable studies of ongoing processes in conscious humans
      and can be used to examine diseased tissue as well as the response to injury.

PMID- 9775229
TI  - Do corneal endothelial dystrophies represent ocular neurocristopathies? A
      discussion on the available evidence.
AB  - Current thinking on the embryological origin of human corneal endothelium has it
      that this cellular population stems from neural crest precursors. There are
      arguments in support of this assumption but equally persuasive ones against it.
      We present a discussion of the evidence for and against a neural crest origin for
      human corneal endothelial cells. In suggesting that caution be applied to
      extrapolating from non-human work, we would question the fallibility of the
      current thinking on this subject. To denote human corneal dystrophies as
      neurocristopathies may be a premature assumption.

PMID- 9775228
TI  - Sclerosing canaliculitis after 5-fluorouracil breast cancer chemotherapy.
AB  - BACKGROUND: 5-Fluorouracil is a pyrimidine analogue that inhibits DNA synthesis
      and is commonly used in the treatment of carcinomas of the breast,
      gastrointestinal tract and genitourinary tract. Excessive tearing that resolves
      on cessation of treatment is commonly described as a side effect of the drug.
      Permanent stenosis of the punctum and canaliculus is extremely rare, with only 12
      cases reported in the world literature. We present three cases of established
      lacrimal outflow obstruction in patients who were treated with CMF
      (cyclophosphamide, methotrexate, 5-fluorouracil), a widely used regimen for
      metastatic breast cancer. Patient 1 had right distal stenosis of her lower
      canaliculus and was syringed patent during dacryocystography with resolution of
      epiphora. Patient 2 had proximal blockage of all canaliculi and underwent
      bilateral canaliculodacryocystorhinostomy with silicone tubes that temporarily
      relieved symptoms until tube removal. The proximal canalicular blockage recurred
      due to underlying extensive fibrosis. Patient 3 had right proximal common
      canalicular stenosis and left distal canalicular blocks but declined surgery.
      CONCLUSION: With the rise in the incidence of breast carcinoma it is important
      that the attention of both ophthalmologists and oncologists should be drawn to
      the potential ocular toxicity of systemic 5-fluorouracil chemotherapy, which may
      lead to lacrimal canalicular fibrosis with permanent epiphora. The management of
      these patients is challenging as there is a continuous spectrum of canalicular
      involvement from focal to diffuse; therefore early referral is recommended.
      Moreover as no consensus has been reached as how best to manage this unique small
      group of patients, we review the literature and discuss the implications for
      treatment.

PMID- 9775230
TI  - Clinical and morphological features of Waardenburg syndrome type II.
AB  - Evaluation of 4-month-old girl who presented with congenital cataracts revealed
      heterochromia iridis, fundus hypopigmentation, residual white forelock and
      sensory neural hearing loss--findings consistent with Waardenburg syndrome type
      II. Bilateral peripheral iridectomies performed at lensectomy provided tissue for
      evaluation. Light microscopy revealed fewer melanocytes in the blue iris than in
      the brown. Electron microscopic examination showed a significant (p = 0.0001)
      reduction in melanosome size in the blue iris, and the nerve endings contained
      fewer vesicles. A defect in neural crest cell migration and melanin synthesis may
      be responsible for the heterochromia iridis seen in Waardenburg syndrome type II.

PMID- 9775231
TI  - Dacryocystorhinostomy in south west England.
AB  - PURPOSE: To assess the pre-operative management, surgical technique employed,
      success rate and patient satisfaction following surgery in patients undergoing
      dacryocystorhinostomy (DCR) in South West England. METHOD: Two hundred and forty
      two patients who underwent DCR were retrospectively studied. A telephone
      questionnaire was used to assess patient satisfaction in 100 patients. RESULTS:
      One hundred and thirteen (46%) patients had nasolacrimal duct obstruction, half
      of whom had a history of dacryocystitis, 70 (29%) had canalicular obstruction and
      8 (3%) had mixed blockage. The site of blockage was not known or recorded in 51
      patients (22%). Seventy-five (31%) patients underwent DCR, 151 (62%) DCR with
      insertion of silicon tubes, 9 (4%) DCR and Lester Jones tube, and 7 (3%)
      canaliculodacryocystorhinostomy (CDCR). Overall an 83.5% success rate was
      reported by the surgeons. The success rate for patients with a history of
      dacryocystitis was 98%, for nasolacrimal duct obstruction 96% and for canalicular
      obstruction 82%. When the site of blockage was not known or recorded the success
      rate was 60%. Where the name of the surgeon was not recorded there was a 15%
      successful outcome. Eighty per cent of patients reported some improvement in
      their symptoms following surgery. CONCLUSIONS: DCR is an effective surgical
      procedure with a high rate of patient satisfaction. Pre-operative identification
      of the site of the blockage is likely to improve surgical outcome.

PMID- 9775232
TI  - Age-related cataract and place of birth.
AB  - Cataract patient data from 13 Australian practitioners were analysed in order to
      compare the distribution of seven principal types of cataract in relation to
      gender, age and place of birth. Relative odds ratios were calculated for age
      matched pairs of three identifiable ethnic groups and each type of cataract. The
      number of statistically significant relative odds ratios far exceeds the
      expectation due to chance. The results suggest a relatively greater risk for
      cortical cataract amongst younger when compared with older groups. In contrast,
      the relative odds ratios for nuclear cataract, independently of age, were
      consistently greater than unity when Australians or Northern Europeans were
      compared with Southern Europeans. There was no gender-based difference in
      cataract type distribution.

PMID- 9775233
TI  - The effects of carotid endarterectomy on ocular haemodynamics.
AB  - PURPOSE: To determine the profile of blood flow velocities and resistive indices
      in the ocular vessels of patients with atherosclerotic carotid disease and
      characterise the effect of endarterectomy on these parameters. METHODS: Following
      a preliminary study on healthy volunteers, ophthalmic colour Doppler ultrasound
      examinations were performed on 27 male and 11 female patients with carotid
      disease. These measurements were compared with central retinal artery perfusion
      pressures and intraoperative internal carotid artery stump pressures. RESULTS:
      Significant changes were seen on the endarterectomised side. The peak systolic
      velocity in the ophthalmic artery, and resistive indices in the ophthalmic
      artery, central retinal artery and nasal posterior ciliary artery, rose from pre
      operative values. No correlation between colour Doppler ultrasound measurements
      and intraoperative internal carotid artery stump pressures was present. When
      compared with ophthalmodynamometry readings, a relationship was noted with
      maximum velocities in the central retinal vein. CONCLUSION: Carotid
      endarterectomy alters the haemodynamics in selected vessels of the ocular
      circulation as measured by colour Doppler ultrasound, but more work is required
      to determine the clinical utility of this investigative modality.

PMID- 9775234
TI  - Is the single use of intraoperative 5-fluorouracil in filtering surgery for high
      risk cases enough?
AB  - PURPOSE: To study the efficacy of the adjunctive use of a single intraoperative
      application of 5-fluorouracil (5FU) in eyes with poor prognoses for a successful
      outcome with a trabeculectomy. METHOD: Twenty-four patients (25 eyes) with a mean
      age of 63.7 +/- 14.7 years (range 27-86 years) and a history of one or more risk
      factors (age < 50 years, more than 3 years on topical medication, a previous
      failed filter, previous cataract surgery, uveitis, neovascular glaucoma)
      underwent trabeculectomy with the intraoperative application of 5FU on a sponge
      (25 mg/ml) for 5 min. The average follow-up was 10.1 +/- 5.5 months. RESULTS: The
      mean pre-operative intraocular pressure (IOP) was 24.7 +/- 6.2 mmHg and the mean
      post-operative IOP was 13.9 +/- 3.5 mmHg. Success, defined as an IOP within
      desired target levels for a particular eye, in the presence of a functioning
      filter, without supplementary medical therapy, was achieved in 56.5% of cases.
      CONCLUSIONS: Our results of successful filters in this group of patients with
      moderate- to high-risk characteristics approach similar figures quoted for
      trabeculectomies without the adjunctive use of intraoperative 5FU in eyes with
      poor prognoses with a similar length of follow-up. Though the numbers are small
      there is a trend that indicates that the intraoperative application of a single
      dose of 5FU alone may not be sufficient in eyes with moderate- to high-risk
      characteristics of failure of a trabeculectomy.

PMID- 9775235
TI  - Long-term follow-up of Molteno drains used in the treatment of glaucoma
      presenting in childhood.
AB  - PURPOSE AND METHODS: This study reviews the long-term follow-up (mean 11.2 years,
      range 9 months to 16 years 9 months) of Molteno drains used in the treatment of
      glaucoma presenting in childhood, in 34 eyes of 25 patients. RESULTS: Intraocular
      pressure control was achieved in 85% of eyes, and vision (where measurable) was
      maintained in 57% of eyes. Seventy-one per cent of eyes required further surgical
      intervention. Thirty-two per cent of these cases were for drain-related problems,
      which may be avoidable with the use of current surgical techniques. The remaining
      interventions were for associated ocular defects, and for problems caused by
      multiple surgical procedures and periods of high intraocular pressure during
      early childhood. CONCLUSIONS: Today the implants are used at an earlier stage in
      the disease process to try to obtain early and definitive IOP control and so help
      to optimise the long-term visual prognosis.

PMID- 9775236
TI  - The effect of timolol drops on respiratory function.
AB  - PURPOSE: Recently, attention has been focused on the adverse drug reactions of
      topical timolol, especially with regard to respiratory function in the elderly.
      This study was designed to assess whether timolol causes an alteration in lung
      function in patients without pre-existing respiratory disease and who have not
      suffered the impact of long-term beta 2 blockade. METHODS: A placebo-controlled
      randomised, double-masked, cross-over study was carried out on 20 ocular
      hypertensive patients with intraocular pressures over 21 mmHg, normal optic discs
      and full visual fields by Humphrey perimetry. Subjects received single-dose units
      of timolol maleate 0.5% drops or normal saline drops. Both were instilled in one
      eye or systemically (sublingually). The peak expiratory flow rate (PFR), forced
      expiratory volume (FEV), vital capacity (VC) and FEV/VC (%) ratio were all
      measured both before and after each type of drop and route of administration.
      RESULTS: Two hours after instillation of timolol there was no change in PFR (p =
      0.67) or VC (p = 0.40), but there was a fall in FEV (p = 0.038) and the FEV/VC
      (%) ratio (p = 0.041). The fall was greatest after topical administration.
      CONCLUSIONS: Our results show that in our group of patients there was a tendency
      towards mild bronchial obstruction after topical timolol, although this was not
      clinically significant.

PMID- 9775238
TI  - Combined phacoemulsification, pars plana vitrectomy, removal of intraocular
      foreign body (IOFB), and primary intraocular lens implantation for patients with
      IOFB and traumatic cataract.
AB  - PURPOSE AND METHODS: Small-incision cataract extraction by phacoemulsification
      through an anterior continuous circular capsulorhexis, pars plana vitrectomy,
      forceps removal of intraocular foreign body (IOFB) and primary intraocular lens
      implantation were performed in 4 eyes (4 patients) with IOFB and traumatic
      cataract, as an emergency combined procedure. RESULTS: At a mean follow-up of
      12.3 months (range 7-19 months) the best corrected visual acuity of the 4 eyes
      ranged from 6/6 to 6/12. The only complication encountered in our series was an
      opacified posterior capsule that developed 10 months post-operatively in one
      case. This was easily dealt with by neodymium:YAG laser capsulotomy, with good
      final visual outcome. CONCLUSIONS: The results of combined one-stage instead of
      sequential surgeries, and phacoemulsification instead of lensectomy or
      extracapsular cataract extraction for patients with IOFB and cataract are
      encouraging. It could be a good option in selected cases. However, the safety and
      efficacy of this combined procedure need to be evaluated further by a larger
      scale, longer follow-up study.

PMID- 9775237
TI  - The effect of intracameral, per-operative antibiotics on microbial contamination
      of anterior chamber aspirates during phacoemulsification.
AB  - PURPOSE: To assess the effect of per-operative antibiotics on contamination of
      anterior chamber (AC) aspirates during phacoemulsification. METHODS: Two hundred
      and twenty patients undergoing phacoemulsification of cataract were randomly
      allocated to receive an irrigation infusion fluid containing either balanced salt
      solution (BSS) alone or BSS with vancomycin (20 mg/l) and gentamicin (8 mg/l)
      during surgery. Conjunctival swabs were obtained from all patients immediately
      before pre-operative preparation. At the end of surgery 20 ml of the AC aspirate
      was sent for direct and enrichment cultures. Qualitative and quantitative
      microbiological studies were undertaken. The chi-squared test was used to compare
      differences between the two groups. RESULTS: There was no significant difference
      between the positive culture rates of the conjunctival swabs (28 vs 27; p > 0.8).
      In the group that received BSS alone there were 22 (20%) positive AC aspirate
      cultures, 18 of which were from enrichment cultures. There were 3 positive (2.7%)
      cultures from the group that received antibiotics added to the BSS (p < 0.0001).
      CONCLUSION: The addition of gentamicin and vancomycin to the irrigation fluid
      during phacoemulsification results in a highly significant reduction in the
      microbial contamination of AC aspirates.

PMID- 9775239
TI  - A prospective controlled study of a 10/0 absorbable polyglactin suture for
      corneal incision phacoemulsification.
AB  - PURPOSE: To evaluate the performance of a 10/0 monofilament absorbable
      polyglactin suture for temporal 5.2 mm corneal incision phacoemulsification.
      METHODS: A prospective randomised controlled study of 49 patients undergoing
      phacoemulsification with a sutured temporal 5.2 mm corneal section was conducted
      to compare the refractive results and complications of a 10/0 monofilament
      absorbable polyglactin suture with 10/0 nylon. RESULTS: Thirty-eight patients
      completed the study. There was no significant difference in induced astigmatism
      between the two groups. All absorbable sutures were intact at 1 week. Six weeks
      post-operatively the absorbable suture was still intact in 1 (6%) patient,
      present but broken in 4 (24%) and completely absent in 12 (70%) patients. All
      polyglactin sutures had been completely absorbed by 12 weeks. Absorption of the
      polyglactin sutures was associated with mild localised corneal haze in 3(18%)
      cases (p = 0.055). One of the 18 patients (6%) in the polyglactin suture group
      presented with iris prolapse associated with knot failure 1 week post
      operatively. There was no significant difference in foreign body symptoms between
      the two groups. CONCLUSIONS: 10/0 polyglactin sutures maintain adequate tensile
      strength during the immediate post-operative period for small incision surgery
      and are associated with minimal induction of astigmatism. Their subsequent
      absorption obviates the need for routine suture removal. Suture absorption is
      well tolerated although in some cases a mild degree of local tissue reaction
      raises concern about possible mechanisms of absorption. The risk of knot failure
      may be reduced by an alternative suture tying technique. 10/0 monofilament
      polyglactin is an attractive option when a suture is required during small
      incision cataract surgery.

PMID- 9775240
TI  - Optimisation of outpatient resource utilisation in cataract management.
AB  - PURPOSE: We assessed whether patients referred with a diagnosis of cataract
      require outpatient assessment before listing for surgery or whether the general
      practitioner could have direct access to the waiting list. We also studied
      whether pre-assessment clinics made a significant difference to management even
      when waiting times were long. METHODS: Data about patients referred with a
      diagnosis of cataract to the Oxford Eye Hospital and associated hospitals were
      collected. Seventy-five patients were prospectively studied and 100 patient
      records were retrospectively analysed. RESULTS: Twenty-six per cent of patients
      had a misdiagnosis or additional problems affecting management. Optometrists
      provided more information than general practitioners, but their diagnostic
      accuracy was equal (73% optometrists, 75% general practitioners). At the pre
      assessment clinic pupil dilatation changed management in only 4% of patients.
      CONCLUSION: Listing patients on the basis of referral letters would be
      inappropriate in 1 in 4 patients. Pre-assessment clinics rarely picked up a
      clinically relevant change. Thus if outpatient consultation included a decision
      on the exact surgical plan including implant power, then pre-assessment clinics
      may not be necessary.

PMID- 9775241
TI  - Local anaesthesia for vitreoretinal surgery: a case-control study of 200 cases.
AB  - PURPOSE: In the United Kingdom the majority of vitreoretinal (VR) surgery is
      performed under general anaesthesia (GA). The aim of this study was to
      demonstrate the scope of local anaesthesia (LA) for VR surgery, to measure the
      acceptance of LA to patients and surgeons and to compare the surgical outcomes,
      complication rates and duration of the surgical procedures under LA and GA.
      METHODS: A case-control study was undertaken to compare 100 cases performed under
      LA with 100 matched cases performed under GA. The matching of cases was based on
      multiple criteria such as configuration and complexity of retinal detachment, the
      involvement of the macula, the number and site of retinal tears, presence and
      severity of proliferative vitreoretinopathy, experience of the surgeon and the
      type of the surgical procedure. A clinical audit was also carried out on 65
      successive patients using a questionnaire to determine the acceptability of LA to
      patients and surgeons. RESULTS: Anatomical and visual success rates, and intra
      operative and post-operative complications, were similar in cases carried out
      under LA and GA. The mean duration of the surgery (excluding anaesthetic time)
      was significantly shorter for LA than GA procedures (p < 0.001). The acceptance
      for LA was high for both patients and the operating surgeons. CONCLUSIONS: We
      found that VR surgery can be safely and efficiently performed under LA. Adoption
      of LA has increased our throughput.

PMID- 9775242
TI  - Vitreolensectomy in Marfan's syndrome.
AB  - PURPOSE: To evaluate the effectiveness of pars plana vitreolensectomy in the
      management of subluxed lenses associated with Marfan's syndrome and to assess the
      need for intraoperative retinal photocoagulation to prevent post-operative
      retinal detachment. METHOD: A retrospective review was carried out of 40 eyes of
      patients with Marfan's syndrome who underwent pars plana vitreolensectomy for
      subluxed lenses. RESULTS: All patients demonstrated stable or improved visual
      acuity following surgery with a low incidence of complications. CONCLUSIONS: Pars
      plana vitreolensectomy is a safe and effective treatment for subluxed lenses in
      patients with Marfan's syndrome. It appears that intraoperative prophylactic
      laser treatment need only be applied to areas of lattice degeneration to limit
      the incidence of post-operative retinal detachment.

PMID- 9775243
TI  - Epiphora: a quick fix?
AB  - PURPOSE: To assess whether any simple, easily performed and minimally invasive
      procedure may help the symptoms of patients with functional nasolacrimal
      obstruction without recourse to elaborate investigation or major surgery. A
      randomised study was performed to assess the success of retropunctal cautery
      (RPC) and one-snip punctoplasty in this condition. METHODS: In the absence of any
      cause for excess lacrimation, eyelid malposition or nasolacrimal obstruction,
      patients underwent either syringing alone (group A, n = 15) or syringing with RPC
      and a one-snip punctoplasty (group B, n = 15). RESULTS: Three months after
      treatment, six patients in group A were improved, compared with 13 in group B
      (Fisher's exact test, p = 0.0096). CONCLUSIONS: We would recommend that patients
      who suffer from a pump or functional nasolacrimal obstruction should receive RPC
      and a one-snip punctoplasty following the demonstration of a patent system on
      syringing. These simple procedures would not impair further investigation or
      lacrimal surgery if required in the future.

PMID- 9775244
TI  - Dark adaptation in early primary biliary cirrhosis.
AB  - BACKGROUND: The role of vitamin A in early primary biliary cirrhosis (PBC)
      remains uncertain. METHODS: We assessed dark adaptation and assayed vitamin-A
      related compounds in 10 patients with early PBC and a group of age- and sex
      matched controls. RESULTS: In patients compared with controls: (i) mean final
      light threshold value was 11.8% greater (p < 0.004), (ii) time taken to see the
      first light stimulus was longer (2.8 +/- 0.6 vs 1.4 +/- 0.2 min, mean +/- SEM; p
      < 0.03) and (iii) sensitivity to light stimuli was impaired after 6 min in the
      dark (p < 0.03). Three patients had an abnormal final light threshold despite
      receiving regular vitamin A; two had a low serum vitamin A. Raised serum
      bilirubin and increased age were the most important determinants of impaired dark
      adaptation. CONCLUSIONS: Patients with early PBC have modestly impaired dark
      adaptation, despite standard vitamin A supplementation, although these changes
      may not have a significant effect on visual function. Vitamin A supplementation
      should be recommended for older patients with jaundice, but its effect should be
      carefully monitored.

PMID- 9775245
TI  - Ophthalmic abnormalities in homocystinuria: the value of screening.
AB  - PURPOSE: Homocystinuria, a genetic metabolic abnormality, eventually causes a
      variety of ocular and other pathologies if not treated. To evaluate the results
      of screening newborns for homocystinuria, we compared ophthalmic outcomes for two
      groups of homocystinuria patients who had been diagnosed either at birth or later
      than 6 weeks. METHODS AND RESULTS: Nineteen patients had been screened and
      diagnosed shortly after birth, with treatment instigated before 6 weeks of age
      (mean follow-up and age 10.8 years; median 11 years). Eight of 17 were myopic; 13
      of 15 had good vision in both eyes; one had lens subluxation. The second group of
      17 patients were diagnosed later than 6 weeks, often (12 patients) because of
      ocular problems (mean follow-up 8.3 years; mean age 19.4 years; median age 16
      years). Visual function varied from 6/6 (4 patients) to less than 6/36 (4
      patients); 3 eyes had no perception of light. Thirteen patients had lens
      subluxation or dislocation. CONCLUSION: Early diagnosis and treatment of
      homocystinuria is advantageous.

PMID- 9775246
TI  - Simultaneous cell cycle and phenotypic analysis of primary uveal melanoma by flow
      cytometry.
AB  - BACKGROUND AND PURPOSE: DNA ploidy and cell cycle measurements of uveal melanoma
      tissue are regarded as having limited prognostic significance. In contrast, dual
      parameter (DNA monoclonal antibody) flow cytometry offers a convenient and rapid
      way to screen tumour samples for a variety of phenotypic markers, whilst
      simultaneously measuring DNA ploidy and cell cycle, and therefore has the
      increased potential to identify clinically relevant indicators of disease
      progression. The aim of the present study was to identify a simple yet robust
      method for isolating, preserving and staining cells that could be analysed by
      flow cytometry. METHODS: Using a simple preparation procedure, a panel of
      membrane-associated antibodies (ICAM-1, W632, HLA-DR) and nuclear or cytoplasmic
      oncoprotein antibodies (c-erbB-2, c-myc, bcl-2, p53), together with positive (PHM
      5) and negative (FITC F(ab')2) controls, were assayed. It was considered
      important to test the protocol with markers expressed on the cell surface, and in
      the cytoplasm and nucleus, so as not to be restrictive and thereby exclude an
      antigen of potential clinical interest. In addition, such panels would also
      enable the generation of a 'phenotypic profile' for each specimen that may reveal
      clinically significant trends. RESULTS: Our results indicate that tissue
      dissociation followed by brief fixation in 1% paraformaldehyde and
      permeabilisation in 70% methanol produces a stable single cell suspension, which
      can subsequently be stained with a wide range of antibodies for the accurate
      identification of cells in a potentially heterogeneous tumour population.
      CONCLUSION: This technology can rapidly identify sub-populations of cells
      expressing differing levels of proteins, which may prove to be indicative of
      disease progression for this aggressive disease.

PMID- 9775247
TI  - Glycoproteins of trabecular meshwork, cornea and sclera.
AB  - PURPOSE: To analyse high-molecular-weight matrix glycoproteins in trabecular
      meshwork, cornea and sclera using SDS/PAGE and immuno- and lectin blotting.
      METHOD: Extracts of normal trabecular meshwork (TM), cornea and sclera were
      analysed under reducing conditions on SDS/ PAGE. Western blots were stained for
      total protein, and major high-molecular-weight components were identified by
      immunoblotting with antibodies to fibronectin (FN) and type VI collagen. Lectin
      blotting with PSA, MPA and DSA identified some of the glycoprotein glycans.
      RESULTS: FN antibody bound to the 240 kDa band in TM, cornea and sclera. Type VI
      collagen antibody bound more strongly to one band and less so to two other bands
      at approximately 200 kDA in normal TM and to a ladder of bands in cornea and
      sclera. PSA and DSA bound at 240, 200 and 140 kDa in TM, cornea and sclera. MPA
      bound at 240, 200 and 140 kDa in TM and at 240, 200 and approximately 120 kDA in
      cornea and sclera. CONCLUSIONS: FN is a component of the band at 240 kDA in TM,
      cornea and sclera. Normal TM was found to contain relatively more of one of the
      isoforms of the alpha 3 (VI) chain whilst cornea and sclera contained all the
      alpha 3 (VI) isoforms. Complex N-linked bi/tri-antennary glycans were localised
      in FN and the alpha 1, alpha 2 and alpha 3 (VI) chains in TM, cornea and sclera.
      O-linked glycans (identified by MPA binding) were located in FN and alpha 3 (VI)
      chains of TM, cornea and sclera.

PMID- 9775248
TI  - Measurement of electrostatic charge on intraocular lenses.
AB  - PURPOSE: An electronic meter that measures electrostatic charge was designed and
      built. The hypothesis tested was that an intraocular lens (IOL) attains a charge
      during handling in the operating theatre and that washing the IOL with balanced
      salt solution (BSS) would result in a reduction in the surface charge. Once
      exposed to the air a charged IOL may attract particulate matter to its surface
      before implantation into the eye. METHODS: This experiment was performed in the
      operating theatre under sterile conditions mimicking cataract surgery. The lens
      box was opened onto a trolley and the lens container opened by a scrubbed
      assistant. The operator (also scrubbed) removed the lens with MacPherson's
      forceps. The charge on the lens was then measured without delay, or after the
      lens had been washed with 1-2 ml of BSS. RESULTS: The mean charge on unwashed
      lenses was 1.43 x 10(-10) C (n = 12) and on washed lenses was 0.59 x 10(-10) C (n
      = 10). The difference in the charges was significant (p = 0.03, unpaired t-test).
      CONCLUSION: Washing of an IOL prior to implantation will reduce the surface
      charge and is therefore also likely to reduce the chance of contamination.

PMID- 9775249
TI  - Immunopathogenesis of conjunctival scarring in trachoma.
AB  - PURPOSE: Trachoma, a chronic follicular conjunctivitis caused by infection with
      Chlamydia trachomatis, is the leading cause of preventable blindness. The
      blinding complications are associated with progressive conjunctival scarring that
      may result from immunologically mediated responses. We studied the processes
      involved in the regulation of inflammation and fibrosis in trachoma by
      investigating the expression of fibrogenic cytokines in the conjunctiva. METHODS:
      We studied conjunctival biopsy specimens obtained from nine subjects with active
      trachoma and from four control subjects. We used immunohistochemical techniques
      and a panel of monoclonal and polyclonal antibodies directed against interleukin
      1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), tumour necrosis factor
      alpha (TNF-alpha) and platelet-derived growth factor (PDGF). In addition, we
      characterised the composition of the inflammatory infiltrate by the use of a
      panel of monoclonal antibodies. Sirius red and Van Gieson stains were used to
      characterise the extent of fibrous tissue in the substantia propria. RESULTS:
      Trachoma specimens showed greater numbers of inflammatory cells than control
      specimens. The expression of cytokines was absent in the normal conjunctiva.
      Cytoplasmic IL-1 alpha and IL-1 beta expression was noted in the conjunctival
      epithelium in all trachoma specimens. IL-1 alpha, IL-1 beta, TNF-alpha and PDGF
      were detected in macrophages infiltrating the substantia propria. B lymphocytes
      predominated over T lymphocytes in six trachoma biopsies with fibrosis confined
      to the deep substantia propria, whereas T lymphocytes predominated over B
      lymphocytes in three biopsies with more extensive fibrosis. In all trachoma
      biopsies helper/inducer T lymphocytes outnumbered suppressor/cytotoxic T
      lymphocytes. CONCLUSIONS: The upregulated local production of IL-1 alpha, IL
      beta, TNF-alpha and PDGF might contribute to conjunctival damage and scarring in
      trachoma.

PMID- 9775250
TI  - Morphological changes of the conjunctival epithelium in contact lens wearers
      evaluated by impression cytology.
AB  - PURPOSE: Conjunctival changes induced by rigid, gas-permeable and soft contact
      lenses (CL) were investigated using impression cytology. A scoring system based
      on seven parameters (specimen cellularity, cell-to-cell contacts,
      nucleus/cytoplasm ratio, chromatin, goblet cell distribution, keratinisation,
      inflammatory cells) was used to evaluate the morphological results. METHODS: One
      hundred and seventy-two CL-wearing eyes and 40 control eyes were examined. The
      population was divided into three groups: group 1, control eyes; group 2,
      asymptomatic CL-wearing eyes; group 3, CL-wearing eyes with intolerance problems.
      Impression cytology was carried out and all specimens were evaluated according to
      a scoring system. RESULTS: Group 1 specimens always showed normal features in the
      conjunctival epithelium. In group 2, rigid and gaspermeable lenses produced
      greater changes in conjunctival morphology than soft lenses, especially as
      regards cellularity, nucleus/cytoplasm ratio, goblet cell distribution and total
      score. On the contrary, in group 3 wearers of soft lenses showed higher partial
      and total scores than wearers of gas-permeable and rigid lenses. CONCLUSIONS: In
      asymptomatic CL wearers conjunctival morphology was better preserved in wearers
      of soft lenses. In patients with intolerance problems, wearers of soft lenses
      showed the worst cytological features. Impression cytology, evaluated with this
      scoring system, can be used to demonstrate epithelial damage occurring in CL
      wearing patients.

PMID- 9775251
TI  - Endoscopic dacryocystorhinostomy: a personal technique.
AB  - Endoscopic dacryocystorhinostomy is a safe, fast and effective method to relieve
      a stenosis distal to the common canaliculus. The technique is described in detail
      with salient anatomical points and pre-operative examination emphasised.

PMID- 9775252
TI  - Retinal capillary microaneurysms. Correction of erroneous attribution: Bader not
      Bowman.

PMID- 9775253
TI  - Bilateral optic neuropathy linked with amiodarone.

PMID- 9775254
TI  - Transient retinal arterial compromise in Graves' orbitopathy.

PMID- 9775255
TI  - Histology of xanthelasma lesion treated by argon laser photocoagulation.

PMID- 9775256
TI  - Central retinal artery occlusion and optic disc drusen.

PMID- 9775257
TI  - Peripapillary lesions causing blind spot enlargement in a case of multiple
      evanescent white spot syndrome.

PMID- 9775258
TI  - Retinal changes associated with tamoxifen treatment for breast cancer.

PMID- 9775259
TI  - Sub-Tenon's versus peribulbar anaesthesia for cataract surgery.

PMID- 9775260
TI  - The presence of congenital hypertrophy of the retinal pigment epithelium in a
      subgroup of patients with adenomatous polyposis coli mutations.

PMID- 9775261
TI  - National survey of local anaesthesia for ocular surgery: early report.

PMID- 9775262
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.

PMID- 9775263
TI  - Prophylactic argon laser retinopexy prior to removal of silicone oil: a pilot
      study.

PMID- 9775264
TI  - Familial deafness associated with iris degeneration and glaucoma.

PMID- 9775265
TI  - Capsulorhexis phymosis following uncomplicated phacoemulsification surgery.

PMID- 9775267
TI  - Endothelial dysfunction in cardiovascular disease.

PMID- 9775268
TI  - Drug use in pregnancy: a multidisciplinary responsibility.

PMID- 9775269
TI  - Endometriosis: a continuing enigma?
AB  - Endometriosis is a common gynaecological disease but remains a poorly understood
      condition. Fundamental questions about the aetiology, pathophysiology, diagnosis,
      natural history and treatment are still unanswered by the extensive research into
      endometriosis. This article will outline present understanding of endometriosis
      and the advances provided by recent research.

PMID- 9775270
TI  - Ovarian cancer: new thoughts on an old problem.
AB  - Although survival in ovarian cancer remains poor, the use of paclitaxel and
      interval debulking surgery are now recognized to prolong survival. Future trials
      addressing the role of surgery, novel applications of chemotherapy, and
      screening, along with care by recognized specialists, may well improve outcome.

PMID- 9775271
TI  - Bacterial vaginosis: its importance in obstetrics.
AB  - Bacterial vaginosis is associated with adverse sequelae, including late
      miscarriage, preterm prelabour rupture of the membranes, chorioamnionitis,
      postpartum endometritis and preterm labour and delivery. It is easy to diagnose
      and treat; intervention reduces the incidence of adverse sequelae. Symptomatic
      women and those who are at increased risk of infectious morbidity should be
      screened.

PMID- 9775272
TI  - Managing miscarriage in early pregnancy assessment units.
AB  - For most women, pregnancy is a significant life event and the prospect of losing
      a baby causes anxiety, stress and grief. Modern treatment of miscarriage should
      provide rapid sympathetic diagnosis and adequate counselling. Early pregnancy
      assessment units benefit patients, staff and the NHS. Many clinicians use medical
      treatment or expectant management, rather than standard surgical evacuation of
      the uterus.

PMID- 9775273
TI  - The state of health and provision of health care in Hong Kong.
AB  - In 1997, Hong Kong became a Special Administrative Region of the People's
      Republic of China. The new government took control of a Western style health-care
      system and a population whose health is comparable to the rest of the developed
      world. This article describes the existing health-care system, the state of
      public health and some of the challenges and opportunities facing the new
      administration.

PMID- 9775274
TI  - Epilepsy--a guide to medical treatment. 2: Non-drug aspects.
AB  - Approximately 30-40% of people with epilepsy continue to have seizures despite
      drug treatment. Factors related to cognitive abilities, physical handicap,
      psychiatric illness and social circumstances are of great importance in the
      overall management.

PMID- 9775275
TI  - Guidelines for the management of Parkinson's disease. The Parkinson's Disease
      Consensus Working Group.
AB  - Parkinson's disease is a chronic and disabling illness and there is currently
      wide variation in its management. This article presents the first UK-specific
      guidelines for the management of Parkinson's disease and it contains a treatment
      decision free to aid the physician in deciding when and how to treat patients. We
      hope this document will prove useful to all those involved in the planning and
      delivery of care to patients with Parkinson's disease.

PMID- 9775276
TI  - Anaesthetic management of the morbidly obese patient.
AB  - Morbidly obese patients are prone to many clinical conditions that can effect
      anaesthesia. Of major concern to the anaesthetist are difficulties with airway
      management and abnormalities of cardiorespiratory function. Safe anaesthesia
      requires an appreciation of potential problems and a thorough understanding of
      the pathophysiological changes that accompany morbid obesity.

PMID- 9775277
TI  - New forms of skin grafting: from the laboratory to the clinic.
AB  - This article reviews current research on skin replacements used in the management
      of extensive burns and in reconstructive surgery. It describes how progress is
      being made in developing both biological skin substitutes and artificial
      materials with the aim of providing skin cover by means other than traditional
      skin grafting.

PMID- 9775278
TI  - Targeting drug delivery and the small airways in asthma.
AB  - This year will see the launch of the first chlorofluorocarbon (CFC)-free
      formulation of beclomethasone. Developed by 3M Health Care, its extrafine
      formulation gives significant benefits resulting from increased lung deposition
      and improved inhaler technology. Its difference from CFC-propelled inhalers is so
      marked that it will challenge views about about the risk-benefit profile of
      beclomethasone.

PMID- 9775279
TI  - Initial assessment of back pain: an overview.
AB  - In any illness, the severity of symptoms and their effect on lifestyle are very
      important to the patient. Pain in the back may indicate simple backache which
      most people have at some time, a number of serious spinal diseases or low back
      disability. It is important to establish to which category a patient belongs, and
      this article will outline some of the methods by which this can be achieved.

PMID- 9775280
TI  - Imaging the bad back: increasing reliance on MRI.
AB  - Magnetic resonance imaging is becoming the key investigation for the 'bad back'.
      With increasing availability and lower costs, it will gradually replace other
      forms of imaging. The current difficulties are to determine which patients most
      deserve this expensive test and at what stage of their illness they should be
      referred. These and other dilemmas are discussed.

PMID- 9775281
TI  - Interpreting measures of treatment effect.
AB  - A confusing number of measures are used to describe the effect sizes from
      clinical trials or systematic reviews. Absolute measures (absolute risk
      reduction, number needed to treat) and relative measures (relative risk
      reduction, relative risk or odds ratio) may give not just different numerical
      answers but convey different messages. This paper describes the role and meaning
      of the different measures, advises on their interpretation, and highlights the
      importance of taking into account the initial risk when assessing effect sizes
      from published studies.

PMID- 9775282
TI  - The GP preregistration house officer: the potential learning experience of
      primary care.
AB  - The New Doctor paper recently published by the General Medical Council outlines
      the primarily educational role of preregistration house officers. This article
      illustrates one innovative way in which this is being implemented simultaneously
      with a significant service provision, often increasing the standard of patient
      care.

PMID- 9775283
TI  - Latex allergy: a life-threatening complication.

PMID- 9775284
TI  - Endothelial dysfunction.

PMID- 9775285
TI  - Psychometric testing.

PMID- 9775286
TI  - Psychiatry, the Internet and the public.

PMID- 9775287
TI  - The molecular genetics of head and neck cancer.

PMID- 9775288
TI  - Study of common aerobic flora of human cerumen.
AB  - Cerumen is the product of the secretion of the sebaceous, ceruminous or apocrine
      glands together with cells exfoliated from the cornified stratum of the
      epithelium of the external auditory canal (EAC). In the present study we
      identified and quantified common flora of human cerumen. The mean count obtained
      was 10(6) microorganisms per ml of cerumen suspension. In 24 pools of cerumen
      (33.3 per cent) the isolates were monomicrobial, Staphylococcus epidermidis (12),
      Corynebacterium spp (10), Staphylococcus aureus (1) and Streptococcus
      saprophyticum (1). In 48 pools (66.6 per cent) we found polymicrobial isolates.
      The most commonly isolated bacteria in these polymicrobial isolates were S.
      epidermidis (35) and Corynebacterium spp. (43). It is noteworthy that there were
      isolates of Candida albicans in three cases; in one case of Pseudomonas stutzeri,
      in one case of Pseudomonas aeruginosa, and, on seven occasions, of S. aureus. The
      organisms isolated as common bacterial components of human cerumen in our
      experience were similar to those found by other authors. However, the mean count
      was much higher. This could be related to climatic conditions and to the length
      of time the cerumen had remained in the external auditory canal.

PMID- 9775289
TI  - Serum antibodies to human herpesvirus 7, human herpesvirus 6 and cytomegalovirus
      in patients with idiopathic facial nerve palsy or sudden deafness.
AB  - The aetiology of idiopathic facial nerve palsy (Bell's palsy) and sudden deafness
      are not known, although viruses have been suspected as a cause of them. We
      investigated the relationship between Bell's palsy or sudden deafness, and
      reactivation of cytomegalovirus, human herpesvirus 6 (HHV-6) and 7 (HHV-7).
      Paired sera were collected from 22 patients with Bell's palsy and 24 patients
      with sudden deafness. IgG antibody titres to HHV-7 were increased in one patient
      with Bell's palsy. IgG antibody titres to HHV-6 were increased in one patient
      with Bell's palsy and two with sudden deafness. IgG antibody titres to
      cytomegalovirus were increased in one patient with sudden deafness. Titres of the
      three viral antibodies were not increased simultaneously in any patients. These
      viruses may contribute to the development of Bell's palsy or sudden deafness in
      some cases. It is, however, unlikely that these viruses are the main cause of
      Bell's palsy and sudden deafness in the majority of patients.

PMID- 9775290
TI  - Interpretation of the dilated pupil during endoscopic sinus surgery.
AB  - This article describes the anatomy of the visual pathways and how they should be
      assessed under anaesthesia. The differential diagnosis of asymmetrical pupils is
      illustrated with clinical examples and a strategy as to how they should be
      examined.

PMID- 9775291
TI  - Aesthesioneuroblastoma.
AB  - Forty patients were treated or followed up for aesthesioneuroblastoma between
      1980 and 1995 at Institut Gustave Roussy, France. There were three T1, seven T2,
      15 T3 and 15 T4 lesions. The cervical metastatic rate at presentation was 18 per
      cent. Distant metastases were detected by bone marrow biopsy and bone scan in
      three patients at presentation. Treatment modalities included surgery alone in
      eight patients, radiotherapy alone in three patients, combined modality surgery
      plus radiotherapy in 11 patients, chemotherapy alone in two patients,
      chemotherapy plus radiotherapy in 10 patients, and multimodality therapy
      chemotherapy plus surgery plus radiotherapy in six patients. The five-year
      survival rate was 51 per cent. Multimodality treatment offered better survival
      (63 per cent at five years) and disease-free interval (54 months). Overall local,
      regional, and distant failure rates were 58 per cent, 15 per cent and 40 per cent
      respectively. Distant metastases commonly occurred in bone (82 per cent).
      Cervical metastasis was an unfavourable prognostic indicator (0 per cent survival
      at two years). In conclusion, aesthesioneuroblastoma is sensitive to chemotherapy
      and radiotherapy. Multimodality therapy should be used initially.

PMID- 9775292
TI  - Immunoglobulin- and complement-coated bacteria in pus from peritonsillar
      abscesses.
AB  - Fifty-five samples of pus were collected from 51 acute, non-perforated, two
      spontaneously ruptured and two recurrent peritonsillar abscesses (35 males and 18
      females; median age 18 years) and analysed regarding (i) aerobic and anaerobic
      bacteria (standard culturing), (ii) morphology of bacteria and inflammatory cells
      (direct microscopy of acridine orange-stained material), and (iii) the percentage
      of bacteria coated with immunoglobulins IgG, secretory IgA (SIgA) and IgM and
      complement cleavage product C3b (immunofluorescence assay). Seventy-one per cent
      of the abscesses harboured a mixed bacterial flora of various aerobes and
      anaerobes. In none of the cases with a single bacterial species (27 per cent)
      could immunoglobulin- or complement-coated bacteria be found. In abscesses with a
      mixed flora, 18 per cent harboured IgG-coated, 15 per cent SIgA-coated, five per
      cent IgM-coated and five per cent C3b-coated bacteria, respectively. All pus
      samples contained inflammatory cells in abundance but they were mostly deformed
      and only occasionally could intracellular bacteria be recognized. Insufficient
      immunoglobulin-coating of bacteria might be an important aetiopathogenic factor
      in the development of a peritonsillar abscess. Bactericide in the abscesses is
      accomplished chiefly by protective mechanisms not dependent on antigen
      recognition by antibodies.

PMID- 9775293
TI  - Laser assisted uvulopalatoplasty: six and eighteen month results.
AB  - Our ongoing evaluation of the results of laser assisted uvulopalatoplasty (LAUP)
      for snoring is presented. Follow-up between 18 and 24 months post-treatment
      completion, of patients with a successful result at six months, reveals that 22
      per cent of these patients suffer failure of snoring control between these two
      evaluation points. This equates to an overall success rate at this time of 55 per
      cent. LAUP, like other surgical remedies for snoring, has a continued relapse
      rate. This must be considered when counselling patients.

PMID- 9775294
TI  - Simple model for teaching myringotomy and aural ventilation tube insertion.
AB  - Aural ventilation tube insertion is the most common otological operation and is
      usually the first operation learnt by trainees. The limited supply of temporal
      bones as well as expensive commercial models hampers training in the procedure.
      This paper describes a simple solution making a model of the ear canal and drum
      out of materials available on an ENT ward.

PMID- 9775295
TI  - Oro-nasal transfer of nasogastric tube following endoscopic placement.
AB  - After placement of a nasogastric tube through a rigid oesophagoscope it is
      necessary to transfer the proximal end from the mouth to the nose. Observation of
      surgeons performing this apparently simple task has indicated that many find it
      somewhat difficult. We describe a simple solution to the problem.

PMID- 9775296
TI  - Cochlear implant failure due to unexpected absence of the eighth nerve--a
      cautionary tale.
AB  - We present a case of bilateral absence of the eighth cranial nerve in the
      internal auditory meatus (IAM). This caused total failure of responses after
      cochlear implantation in a six-year-old patient with congenital deafness. Pre
      operative magnetic resonance (MR) imaging is important to show not only the
      anatomy of the middle and inner ears but also the structures in the IAM.

PMID- 9775297
TI  - Unusual lesions of the internal auditory canal.
AB  - Acoustic neuromata (AN) account for nearly 90 per cent of internal auditory canal
      (IAC) and cerebello-pontine angle (CPA) tumours. The second most common tumour is
      meningioma. Rare lesions include primary cholesteatoma, facial neuroma, lipoma,
      angioma and various cysts. Two cases of IAC tumour are presented, one of
      hamartoma in which smooth muscle was prominent and the other of lymphangioma. Of
      interest are the specific clinical and radiological features associated with
      these lesions.

PMID- 9775298
TI  - Idiopathic CSF rhinorrhoea presenting with tension pneumocephalus and
      hemiparesis.
AB  - A case of non-traumatic/non-iatrogenic CSF rhinorrhoea, presenting with tension
      pneumocephalus and hemiparesis is described. The possible pathological processes
      involved in this rare case are discussed. Cases in the literature of idiopathic
      CSF rhinorrhoea and also those of spontaneous pneumocephalus are reviewed.

PMID- 9775299
TI  - The management of massive pneumocephalus and cerebrospinal fluid rhinorrhoea as a
      consequence of biopsy in a patient with inverted papilloma.
AB  - Nasal polypectomy is a common ENT operation. Cerebrospinal fluid (CSF)
      rhinorrhoea and pneumocephalus are rare complications. We present a patient who
      developed both these complications after biopsy of nasal polyps which
      subsequently proved to be an inverted papilloma. He had a defect in the ethmoid
      roof, which was repaired. Whilst endoscopic repair of CSF leak is increasing in
      popularity, in this patient because of his pathology and difficulty of access a
      more traditional lateral rhinotomy approach was made with a successful outcome.
      An overview of the management of these complications is presented.

PMID- 9775300
TI  - Isolated sphenoethmoid recess polyps.
AB  - Isolated sphenoethmoid recess (SER) polyps are rare. They usually arise from the
      sphenoid sinus. We report six patients with SER polyps as the only abnormal
      clinical finding at initial presentation. All cases were investigated with
      outpatient biopsy and computed tomography (CT) or magnetic resonance (MR)
      imaging. Pre-operative histology revealed three cases of inflammatory disease,
      two cases with inverted papilloma, and one case of an ectopic pituitary adenoma
      arising from the sphenoid sinus. One of the inflammatory polyps arose directly
      from the mucosa around the sphenoid ostium. The other five cases involved the
      sphenoid sinus. Except for the ectopic pituitary adenoma all the polyps were
      managed by transnasal endoscopic surgery. We emphasize that isolated SER polyps
      may signify existing sphenoid pathology and a pre-operative biopsy is valuable
      for planning surgery.

PMID- 9775301
TI  - Wegener's granulomatosis. First case report in Bahrain.
AB  - Formerly a fatal condition, Wegener's granulomatosis is now treated with good
      results. Although the annual incidence of Wegener's granulomatosis in the general
      population is not known, most European and American studies revealed an incidence
      in the range of one for every 250,000 of the population. The estimated total
      population of Bahrain as of June 1997 is 586,110; here we report the first
      diagnosed case of Wegener's granulomatosis in Bahrain. Our patient presented with
      epistaxis, and from the clinical features, the very high ESR, the operative,
      histopathological and the radiological findings, and a high index of suspicion we
      could confirm the diagnosis along with the appropriate immunological test
      (positive cANCA). Standard treatment with cytotoxic agents and corticosteroids
      has been used. On follow-up the patient has shown a progressive improvement in
      her clinical and laboratory parameters.

PMID- 9775302
TI  - Choroid metastasis of undifferentiated nasopharyngeal carcinoma.
AB  - Choroid metastasis of primary nasopharyngeal carcinoma is an infrequent event.
      Here, we report a case of nasopharyngeal carcinoma with metastases to the choroid
      successfully treated by external beam radiotherapy.

PMID- 9775303
TI  - Laryngeal rhabdomyosarcoma in adults.
AB  - Laryngeal rhabdomyosarcoma is a rare disease. Only nine of these tumours have
      been adequately described in world literature in the adult population. Adult
      patients with laryngeal rhabdomyosarcoma often present at a later stage than
      other laryngeal tumours, including squamous cell carcinoma. Diagnosis is made by
      identification of cross-striations histochemically or cytoplasmic myoglobin by
      immunohistological methods. We present a 66-year-old woman with pleomorphic
      rhabdomyosarcoma of her larynx. This is the first female in the adult age group
      to be presented. Surgical treatment with adjuvant radiotherapy is currently the
      treatment of choice for this disease. We provide a review of the literature on
      laryngeal rhabdomyosarcoma, including presentation, pathology and management of
      this rare disease.

PMID- 9775305
TI  - A palatal haemangioma in a child.
AB  - Haemangiomas are the commonest benign tumours of the head and neck in childhood,
      but they are extremely rate on the palate. We report a case of a palatal
      haemangioma presenting with feeding difficulties in a young infant. Clinical
      diagnosis and pathological features are discussed and we suggest a classification
      which may help in the diagnosis of these cases.

PMID- 9775304
TI  - Intralaryngotracheal thyroid--ectopic thyroid or invasive carcinoma?
AB  - Intralaryngotracheal thyroid is a rare clinical condition with only about 125
      cases described so far in the literature. We present an unusual case of
      intralaryngotracheal thyroid which had many clinical features of malignancy and
      yet appeared benign on histology. As in this case, well-differentiated thyroid
      cancer can present with locally aggressive clinical features and can pose a
      dilemma in management if treatment decisions are guided solely by histological
      features.

PMID- 9775306
TI  - Idiopathic diffuse erosion of the skull base presenting as cerebrospinal fluid
      rhinorrhoea.
AB  - We present an unusual case of generalized erosion of the skull base. We have not
      found a similar case reported in the world literature. The presenting symptom was
      spontaneous cerebrospinal fluid (CSF) rhinorrhoea which arose from a bony defect
      associated with herniation of the right temporal lobe into the sphenoid sinus. We
      discuss the management of such a case including imaging of the skull base and the
      endoscopic repair of the bony defect.

PMID- 9775307
TI  - Teratocarcinosarcoma of the nasal cavity and ethmoid.
AB  - Sinonasal teratocarcinosarcoma is very unusual malignant neoplasm histologically
      consisting of an epithelial element and one or more mesenchymal components. This
      is a report of teratocarcinosarcoma, in a 74-year-old male, involving the right
      nasal cavity and ethmoids with intracranial extension. The tumour was totally
      resected via the craniofacial approach and the patient was given post-operative
      chemotherapy. Extensive tumour necrosis, rapid growth and local destruction are
      the prominent features of this tumour. The clinical presentation, pathological
      features and clinical course of this rare malignancy are discussed with a review
      of the literature.

PMID- 9775308
TI  - Focal myositis of the sternocleidomastoid muscle.
AB  - Focal myositis is an unusual inflammatory lesion of skeletal muscle. It usually
      affects the extremities, but can present rarely in the head and neck region. We
      present a case of an elderly woman with focal myositis of the sternocleidomastoid
      muscle and review of the previous literature on this subject.

PMID- 9775309
TI  - The Cartesian Broadway.

PMID- 9775310
TI  - Stereoscopic discrimination of interval and ordinal depth relations on smooth
      surfaces and in empty space.
AB  - In a series of three experiments, observers judged the perceived relative depths
      of small probe dots, which could be presented in empty space or attached to a
      smoothly curved surface. Discriminations of ordinal depth were found to be more
      precise than discriminations of depth intervals. The amount of separation in the
      projected image between the locations in depth was also manipulated. Performance
      was higher when observers evaluated the depth relationships between nearby points
      in the projected images, and lower when the points were more widely separated.
      This effect was most pronounced when there was a continuous surface in between
      the points, suggesting that accurate knowledge of the three-dimensional structure
      of surfaces is primarily limited to relatively small local neighborhoods.

PMID- 9775311
TI  - On the relative salience of Euclidean, affine, and topological structure for 3-D
      form discrimination.
AB  - A match-to-sample task was performed, in which observers compared configurations
      of line segments presented stereoscopically in different three-dimensional
      orientations. Several different structural properties of these configurations
      were manipulated, including the relative orientations of line segments (a
      Euclidean property), their coplanarity (an affine property), and their patterns
      of cointersection (a topological property). Although the differences in these
      properties to be detected were all metrically equivalent, they varied
      dramatically in their relative perceptual salience, such that the error rates and
      reaction times in the three conditions varied by as much as 400%. Performance was
      highest in the topological condition, intermediate in the affine condition, and
      lowest in the Euclidean condition. These findings suggest that the relative
      perceptual salience of object properties may be systematically related to their
      structural stability under change, in a manner that is similar to the Klein
      hierarchy of geometries.

PMID- 9775312
TI  - The role of typical contours in the encodement of objects in three-dimensional
      arrays.
AB  - Two experiments are reported in which the relationship between the orientation of
      the typical contour of a lamella in relation to the observer, and the ability of
      the observer to learn the correct position and orientation of sets of lamellae in
      three-dimensional arrays, was examined. For lamellae presented with their typical
      contour in a plane other than the observer's frontoparallel plane, the results of
      both experiments indicated that participants encoded lamellae in such a way that
      their typical contour appeared to be closer to the observer's frontoparallel
      plane than the respective stimulus. The relationship of the present findings to
      previous results on children's drawings and to the concept of the picture plane
      are considered.

PMID- 9775313
TI  - The influence of feature-based information in the age processing of unfamiliar
      faces.
AB  - The influence of the internal features (eyes, nose, and mouth) in the age
      processing of unfamiliar faces was examined. Younger and older versions of the
      faces of six individuals (covering three different age ranges, from infancy to
      maturity) were used as donor stimuli. For each individual in turn, the effects on
      age estimates of placing older features in the younger face version (or vice
      versa) were investigated. Age estimates were heavily influenced by the age of the
      internal facial features. Experiment 2 replicated these effects with a larger
      number of faces within a narrower age range (after growth is complete and before
      major skin changes have occurred). Taken together, these two experiments show
      that the internal facial features may be influential in conveying age information
      to the perceiver. However, the mechanisms by which features exert their influence
      remain difficult to determine: although age estimates might be based on local
      information from the features themselves, an alternative possibility is that
      featural changes indirectly influence age estimates by altering the global three
      dimensional shape of the head.

PMID- 9775315
TI  - Can illusory figures be transparent and opaque at the same time?

PMID- 9775314
TI  - Illusory-contour formation affected by luminance contrast polarity.
AB  - We report a new type of illusory contour (Illusory-O) whose formation is
      contingent upon the contrast polarity of its juxtaposed inducing elements being
      similar, i.e. both elements must either be positive or negative in contrast sign.
      To test the hypothesis that this contingency is primarily dictated by factors
      that determine amodal surface completion (occlusion) between the inducing
      elements we conducted a series of experiments employing known spatial properties
      of the amodal completion mechanism, to show that spatial conditions unfavorable
      to occlusion lead to a concurrent weakening of the Illusory-O formation. For
      instance, we found that when the juxtaposed inducing elements (solid rectangles)
      were spatially misaligned, or when their spatial separation increased, our
      observers rated the perception of the Illusory-O as reduced. We also showed that,
      in addition to using solid-form inducing elements, the Illusory-O can be induced
      by line terminals, as long as these lines respect the requirements of the amodal
      completion mechanism such as similar contrast polarity and spatial alignment.
      Then we demonstrated that the role of the amodal completion mechanism is not
      limited to our particular arrangement of inducing elements by showing that the
      formation of the illusory Necker cube also relies on similar contrast polarity.
      Finally, to explain why some illusory contours like the Illusory-O are dependent
      on contrast polarity while others (e.g. Kanizsa square) are not, we propose that
      the key rests upon the visual system's presumption of occlusion. That is, in
      forming the illusory contour, if the visual system infers that it is a byproduct
      of the inducing elements being occluded, then having inducing elements of similar
      contrast polarity becomes a prerequisite. This assumption can be traced to the
      occurrence in the real world where partially occluded objects usually have
      visible parts (on both ends) with similar contrast polarity. Along this line of
      thinking, we suggest a plausible neural circuitry that may be implemented to form
      both contrast polarity sensitive and insensitive types of illusory contours.

PMID- 9775316
TI  - Young infants' perception of illusory contours in dynamic displays.
AB  - Ninety-six 4-month-old infants were habituated to one of three computer-generated
      displays depicting two rod parts above and below an occluding box. In the first
      display, the surfaces and boundaries of the rod and box were specified by dense
      surface texture. Their depth segregation was specified by accretion and deletion
      of background texture and motion shear. In the second display, the unity of the
      rod parts and box, and their depth segregation, were specified only by illusory
      contours. In the third display, the boundaries of the rod and box were specified
      by illusory contours, perceptible only via spatiotemporal integration of
      accretion and deletion of sparse-background-texture elements. Infants appeared to
      perceive object unity, and segregate the rod and box surfaces, in all three
      displays, indicating use of illusory contours to perceive bounded surfaces in
      depth. The results suggest a cognitive contribution to perception of some
      illusory contours, abilities which seem to be present by at least 4 months of
      age.

PMID- 9775317
TI  - The role of binocular viewing in a spacing illusion arising in a darkened
      surround.
AB  - A study is reported of the binocular-oculomotor hypothesis of the moon illusion.
      In a dark hall, a pair of light points was presented straight ahead horizontally,
      and another pair was presented at the same distance but 50 degrees upward. Twenty
      subjects compared the spacings of these two pairs. Half of the subjects viewed
      the stimuli first monocularly and then binocularly, and the other half viewed
      them in the reverse order. Eye position was also systematically varied, either
      level or elevated. A spacing illusion was consistently obtained during binocular
      viewing (with the upper spacing seen as smaller), but no illusion arose during
      monocular viewing unless it was preceded by binocular viewing. Furthermore, an
      enhancement of the illusion due to eye elevation was found only during binocular
      viewing. These findings replicate the report of Taylor and Boring (1942 American
      Journal of Psychology 55 189-201), in which the moon was used as the stimulus,
      and support the binocular-oculomotor hypothesis as a partial explanation for the
      moon illusion.

PMID- 9775318
TI  - Linear-vection chronometry along spinal and sagittal axes in erect man.
AB  - The present study investigates the onset latencies for linear vection along both
      the spinal and the sagittal axis in erect human adults. For each axis, both
      directions have been investigated (upward vs downward, forward vs backward). The
      vection-onset latency is thought to be shortened by the decrease of the conflict
      between visual and vestibular afferents. Since this sensory conflict can be
      presumed to be more important in the horizontal sagittal axis than in the
      vertical spinal one, the vection-onset latencies have been hypothesised to be
      longer in the former case than in the latter. Additionally, since the magnitude
      of this sensory conflict can be presumed to be the same between the two opposite
      directions within each axis, the vection-onset latencies have been expected not
      to vary between directions within each axis. The results confirm both these
      hypotheses.

PMID- 9775319
TI  - The pupil response of a teleost fish, Porichthys notatus: description and
      comparison to other species.
AB  - The pupil response of Porichthys notatus to different intensities of illumination
      is described and compared to that of P. myriaster, Cephaloscyllium ventroisum,
      and a human. While the fully dark adapted pupil is round, at the highest light
      intensities it consists of only two small, almost independent, apertures with a
      total area 4.9% of that observed in the fully dilated animal. The response is at
      least partially consensual and occurs, albeit at a much reduced rate, in isolated
      eyes. P. notatus also displays retinomotor movements comparable to those seen in
      most teleosts, suggesting that, contrary to most previous assumptions, pupillary
      responses and retinomotor migrations are not mutually exclusive.

PMID- 9775320
TI  - The effect of forced vergence on retinal correspondence.
AB  - The spatial characteristics of the changes in retinal correspondence produced by
      forced convergence were studied. The vertical extent of lateral shifts in
      binocular correspondence were quantified by comparing the convergence of the eyes
      measured with binocular search coils to the convergence of the eyes as determined
      using nonius lines having vertical separations (gaps) between the nonius lines of
      0.5-4.8 degrees. Lateral shifts in binocular correspondence only occurred for
      nonius gaps < 3-4 degrees. The effects of horizontal retinal eccentricity on
      lateral shifts in correspondence were determined by measuring the nonius horopter
      of the subject under forced convergence, using 11 nonius line eccentricities
      between 4.5 degrees left and right. The nonius horopter was shifted toward the
      fusion target maximally near the fixation point. There was no shift beyond 3
      degrees of eccentricity. We conclude that the nonius horopter is 'dimpled'
      vertically and horizontally, facilitating local fusion by shifting the line
      horopter and the region of single binocular vision toward the point of regard
      over a region of 3 degrees around the fixation point.

PMID- 9775321
TI  - Perceptual filling-in: a parametric study.
AB  - We studied perceptual filling-in during maintained peripheral viewing of a
      uniform gray or red figure presented on a large textured background. Changes in
      the figure's size, shape, and eccentricity caused variations in the time required
      for filling-in that could be predicted from the size of its cortical projection
      within early visual areas. The data suggest that the time which elapsed before
      the figure was filled-in by its background reflects the time required for figure
      ground segregation to fail, rather than a slow spread of the background across
      the figure. Our findings reveal interactions between surface segregation and
      filling-in which may be at the basis of normal surface perception.

PMID- 9775322
TI  - Dynamics of a divisive gain control in human vision.
AB  - Evidence for a divisive contrast gain control in human vision was obtained using
      a contrast version of the probe-on-flash technique that has been employed in the
      light adaptation literature. Thresholds were measured for a briefly flashed (30
      ms), vertical test pattern superimposed on a cosine mask as a function of time
      after mask onset (SOA). Threshold elevations declined monotonically for SOAs up
      to 150 ms. and exhibited an exponential time course with an average time constant
      of 51 ms. Increment thresholds for the test as a function of mask contrast
      provide direct evidence that these effects are due to operation of a divisive
      gain control within the first 150 ms after stimulus onset. Experiments to measure
      the spatial spread of this gain control show it to be localized to a region of no
      more than 45 arc min radius.

PMID- 9775323
TI  - Visual field extent in children 3.5-30 months of age tested with a double-arc LED
      perimeter.
AB  - Visual field extent along the four diagonal meridia was measured cross
      sectionally in 180 normal children (infants and toddlers), and 22 adults. Infants
      were tested monocularly at 3.5, 7, or 9 months, and toddlers were tested
      binocularly at 11, 17, or 30 months. Adult control data were obtained under
      monocular viewing. Three testing methods were investigated: static and hybrid
      static-kinetic perimetry, using LED arrays under computer control, and kinetic
      perimetry, using white styrofoam spheres manipulated by hand. Data analysis
      included corrections for false positives in the method of constant stimuli and
      for errors of anticipation in the ascending method of limits. Across all data
      sets from children, kinetic perimetry yielded larger, more adult-like fields,
      which approached adult levels around 17 months, whereas static and hybrid static
      kinetic perimetry yielded smaller visual fields, approaching adult levels only at
      30 months.

PMID- 9775324
TI  - Dynamic asymmetries in disparity convergence eye movements.
AB  - Vergence eye movements have traditionally been considered the product of a single
      neural control center and are usually studied by combining the movements of each
      eye into a single 'vergence' response. In the present experiment, disparity
      driven eye movements were produced by symmetrical step stimuli, and the dynamic
      properties of each eye movement were analyzed separately. Although the final
      positions of the two eyes were symmetrical, large dynamic asymmetries often
      occurred. The timing between the two eyes showed fair synchrony as they attained
      maximum velocity at approximately the same time. Since the final static positions
      were symmetrical, asymmetries occurring during the initial dynamic component must
      necessarily be compensated by offsetting asymmetries in the latter portion of the
      response.

PMID- 9775325
TI  - Neural dynamics of motion processing and speed discrimination.
AB  - A neural network model of visual motion perception and speed discrimination is
      presented. The model shows how a distributed population code of speed tuning,
      that realizes a size-speed correlation, can be derived from the simplest
      mechanisms whereby activations of multiple spatially short-range filters of
      different size are transformed into speed-turned cell responses. These mechanisms
      use transient cell responses to moving stimuli, output thresholds that covary
      with filter size, and competition. These mechanisms are proposed to occur in the
      V1-->MT cortical processing stream. The model reproduces empirically derived
      speed discrimination curves and simulates data showing how visual speed
      perception and discrimination can be affected by stimulus contrast, duration, dot
      density and spatial frequency. Model motion mechanisms are analogous to
      mechanisms that have been used to model 3-D form and figure-ground perception.
      The model forms the front end of a larger motion processing system that has been
      used to simulate how global motion capture occurs, and how spatial attention is
      drawn to moving forms. It provides a computational foundation for an emerging
      neural theory of 3-D form and motion perception.

PMID- 9775326
TI  - A biophysical model for the developmental time course of retinal orientation
      selectivity.
AB  - A quantitative study of the time course of development of the percentage of
      orientationally selective and isotropic ganglion cells in turtle retina has
      recently been performed. This study revealed that as soon as ganglion cells start
      responding to light, a large percentage of them are selective to the orientations
      of moving visual stimuli. This percentage decreases with age to reach a minimum
      around hatching, increases dramatically after birth and finally, decreases again
      following the first month of life to reach adult level. Concomitantly, the
      percentage of cells responding isotropically to the orientation of elongated
      stimuli increases monotonically until about 30 days after birth, stabilizing
      afterwards. To account for both time courses, we propose a biophysical model
      implementing features ubiquitous to developing vertebrate retinas. These features
      include early dendritic and synaptic spatial polarization, dendritic growth, and
      waves of activity generated spontaneously or by visual stimulation sweeping
      across the inner plexiform layer (IPL). The model also assumes a physiologically
      plausible Hebbian rule, which includes long-term potentiation and depression.
      Computer simulations of this model yield good fits of the data. The quality of
      these fits confirms and extends results from an earlier model using
      computationally-simple mechanisms, which suggested that early dendritic
      polarization might be the seed for mature orientation selectivity.

PMID- 9775327
TI  - Second-order motions contribute to vection.
AB  - First- and second-order motions differ in their ability to induce motion
      aftereffects (MAEs) and the kinetic depth effect (KDE). To test whether second
      order stimuli support computations relating to motion-in-depth we examined the
      vection illusion (illusory self motion induced by image flow) using a vection
      stimulus (V, expanding concentric rings) that depicted a linear path through a
      circular tunnel. The set of vection stimuli contained differing amounts of first-
      and second-order motion energy (ME). Subjects reported the duration of the
      perceived MAEs and the duration of their vection percept. In Experiment 1 both
      MAEs and vection durations were longest when the first-order (Fourier) components
      of V were present in the stimulus. In Experiment 2, V was multiplicatively
      combined with static noise carriers having different check sizes. The amount of
      first-order ME associated with V increases with check size. MAEs were found to
      increase with check size but vection durations were unaffected. In general MAEs
      depend on the amount of first-order ME present in the signal. Vection, on the
      other hand, appears to depend on a representation of image flow that combines
      first- and second-order ME.

PMID- 9775328
TI  - Observer biases in the 3D interpretation of line drawings.
AB  - Line drawings produced by contours traced on a surface can produce a vivid
      impression of the surface shape. The stability of this perception is notable
      considering that the information provided by the surface contours is quite
      ambiguous. We have studied the stability of line drawing perception from
      psychophysical and computational standpoints. For a given family of simple line
      drawings, human observers could perceive the drawings as depicting either an
      elliptic (egg-shaped) or hyperbolic (saddle-shaped) smooth surface patch.
      Rotation of the image along the line of sight and change in aspect ratio of the
      line drawing could bias the observer toward either interpretation. The results
      were modeled by a simple Bayesian observer that computes the probability to
      choose either interpretation given the information in the image and prior
      preferences. The model's decision rule is noncommitting: for a given input image
      its responses are still probabilistic, reflecting variability in the modeled
      observers' judgements. A good fit to the data was obtained when three observer
      assumptions were introduced: a preference for convex surfaces, a preference for
      surface contours aligned with the principal lines of curvature, and a preference
      for a surface orientation consistent with an object viewed from above. We discuss
      how these assumptions might reflect regularities of the visual world.

PMID- 9775329
TI  - OKN, perceptual and VEP direction biases in strabismus.
AB  - The present study quantified nasalward/temporalward biases in monocular
      optokinetic nystagmus (MOKN) and perceived velocity in patients with either early
      onset esotropia, late onset esotropia and in normals. MOKN was measured with low
      spatial frequency, small-field gratings drifting at 9.4 degrees/s. MOKN bias was
      quantified as the ratio of nasalward slow-phase velocity divided by the sum of
      temporalward and nasalward slow-phase velocities (N/(N + T)). Observers also
      rated the perceived velocity of gratings moving in nasalward and temporalward
      directions (3 or 9.4 degrees/s) using a two interval forced choice task. MOKN and
      perceived velocity biases were correlated negatively in both early onset and late
      onset groups in the perceptual task--nasalward moving targets were rated as
      slower than temporalward targets, but in the MOKN task, slow-phase gain was
      higher for nasalward than for temporalward targets. Oscillatory-motion, visual
      evoked potentials (VEPs), were recorded in response to 1 c/deg gratings
      undergoing apparent motion at 10 Hz in a subset of the observers. VEP direction
      biases were quantified by calculating the ratio of first harmonic response
      amplitudes to the sum of first and second harmonic amplitudes. Significant
      correlations were found between the direction biases obtained on all three
      measures. Perceived velocity and MOKN bias measures were also correlated
      negatively. Patients with early onset esotropia (infantile esotropia) had larger
      biases than late onset esotropes or normals on each measure and the biases were
      more frequently bilateral in the early onset patients. The pattern of result is
      consistent with early critical periods for the mechanism(s) underlying MOKN,
      perceived velocity and cortical responsiveness. A single site model for all three
      asymmetries is unlikely, at least in simple form, because of the negative
      correlation between MOKN and perceived velocity biases and because of the
      differences in relative magnitude between the perceptual and MOKN biases.

PMID- 9775330
TI  - Theoretical and practical performance of a concentric bifocal intraocular implant
      lens.
AB  - Some results from a survey of 43 patients who had a monofocal intra-ocular-lens
      (IOL) in one eye and a concentric bifocal intra-ocular-lens in the fellow eye are
      reported. Twenty patients with 6/9 or better post-operative visual acuity in both
      eyes, participated in the main part of the study. Optical transfer functions for
      the bifocal lens showed that, compared to an optimal single-vision correction,
      there is a 50% contrast degradation of the distance retinal image across all
      spatial frequencies above around 3 c/deg. For the patients in the main study,
      there was a close correspondence between practical measurement of contrast
      sensitivity and the theoretical predictions of the modulation transfer functions.
      Measuring contrast sensitivity proved an effective means of assessing
      misalignment of the bifocal IOLs.

PMID- 9775331
TI  - Inversion superiority in visual agnosia may be common to a variety of orientation
      polarised objects besides faces.
AB  - Selective impairment in recognition of faces (prosopagnosia) resulting from
      certain localized cortical lesions has been advanced as an argument for a face
      specific brain module. The argument is claimed to be strengthened by the
      discovery of an inversion superiority effect in the recognition of faces by a
      prosopagnosic patient (Farah et al., Vis Res 1995b;35:2089-2093). The present
      paper reports an inversion superiority effect in the recognition of faces and
      shoes in a visual agnosic patient. The finding raises the possibility that
      several classes of orientationally polarized objects, of which shoes and faces
      are examples, will exhibit inversion superiority.

PMID- 9775332
TI  - Thalidomide approval brings tight restrictions on access.

PMID- 9775333
TI  - San Diego VA pharmacists find room in ambulatory care clinics.

PMID- 9775334
TI  - In patients with chronic diseases, unrelated disorders may go untreated.

PMID- 9775335
TI  - Marketing could be primary objective of managed care health promotion programs.

PMID- 9775336
TI  - Patients, more than physicians, frown on drug company freebies.

PMID- 9775337
TI  - Learning how to use ASHP's Clinical Skills Program.

PMID- 9775338
TI  - Realizing pharmacists' potential in the outpatient clinic arena.

PMID- 9775339
TI  - Identifying ambulatory care patients with coronary heart disease who need
      cholesterol management.

PMID- 9775340
TI  - Docetaxel: a taxoid for the treatment of metastatic breast cancer.
AB  - The pharmacology, pharmacokinetics, clinical trials, adverse effects, and dosage
      and administration of docetaxel are reviewed. Docetaxel, a taxoid for the
      treatment of metastatic breast cancer, blocks the ability of tumor cells to
      divide in the M phase of the cell cycle. The drug has demonstrated superior
      cytotoxic activity in the treatment of a variety of cancers and enhanced activity
      in combination with other drugs. The pharmacokinetics of docetaxel appear to be
      linear. There seems to be a large interpatient variation in docetaxel
      biotransformation rates. Docetaxel has FDA-approved labeling for use in the
      treatment of patients with locally advanced or metastatic breast cancer whose
      disease has progressed during anthracycline-based therapy or who have relapsed
      during anthracycline-based adjuvant therapy. Phase II trials established the
      drug's role in first-line and second-line treatment of advanced breast cancer and
      as therapy for anthracycline-resistant advanced breast cancer, and they suggested
      a role for the agent in combination chemotherapy. The dose-limiting toxicity in
      all studies has been neutropenia. Other commonly noted adverse effects include
      mucositis, hypersensitivity reactions, and neuropathy. The recommended dosage for
      patients with metastatic or locally advanced breast cancer and normal hepatic
      function is 60-100 mg/m2 i.v. infused over one hour every three weeks. Docetaxel
      is not recommended for patients with liver metastases or impaired liver function
      because clearance of the drug is impaired. Docetaxel is effective in the
      treatment of metastatic and anthracycline-resistant breast cancer and may have a
      role in combination with other agents and in neoadjuvant and adjuvant therapy.

PMID- 9775341
TI  - Staff development in pharmacist-conducted patient education and counseling.
AB  - A staff development program designed to improve pharmacists' counseling skills
      and to allow participants to achieve a minimum level of competence in counseling
      is described. The pharmacy service at a Department of Veterans Affairs medical
      center selected a workshop emphasizing the principles of the Indian Health
      Service (IHS) interactive counseling technique as the basis for a training
      program for staff pharmacists. The program was expanded to meet the pharmacy's
      counseling training needs. Handouts on 70 of the most frequently prescribed
      outpatient medications; administration techniques for oral and nasal inhalers and
      ophthalmic agents; and 32 common diseases were included in training manuals.
      Seven standard cases were developed for role-playing sessions, the purpose of
      which was to increase pharmacists' level of confidence in using the IHS technique
      and in counseling patients about common diseases and medications. Each
      pharmacist's counseling technique was assessed by a facilitator. Knowledge of
      commonly prescribed medications was assessed by an open-book written examination.
      The pharmacists' self-reported level of confidence in counseling patients about
      common diseases and medications was significantly improved after the training
      program. A counseling training program enabled pharmacists to achieve a minimum
      level of competence in counseling and increased their confidence in their
      counseling skills.

PMID- 9775342
TI  - Attitudes of Ohio hospital pharmacy directors toward national voluntary pharmacy
      technician certification.
AB  - Ohio pharmacy directors' attitudes about national voluntary pharmacy technician
      certification were surveyed. In May 1996 a questionnaire was mailed to all 224
      hospitals in Ohio. The questionnaire contained 29 attitudinal statements
      constructed as forecasts of the effects of certification; pharmacy directors were
      asked to rate their level of agreement or disagreement with each statement using
      a 7-point Likert scale. The response rate was 61.4% (137 questionnaires
      returned). Respondents indicated modest agreement with 21 of 27 attitudinal
      statements and therefore had a generally positive view of certification. For
      example, they agreed that certification will improve technicians' knowledge,
      image, confidence, skills, and job satisfaction. They disagreed that
      certification will allow technicians to function independently, result in the
      replacement of pharmacist positions with technicians, or eliminate the need for
      on-the-job training of technicians. There were significant differences in scores
      between directors working at hospitals employing certified technicians and
      directors working at hospitals not employing certified technicians for only three
      statements. Overall, Ohio hospital pharmacy directors had positive attitudes
      about pharmacy technician certification.

PMID- 9775344
TI  - Pharmacy technicians as members of care teams.

PMID- 9775343
TI  - Stability of bethanechol chloride, pyrazinamide, quinidine sulfate, rifampin, and
      tetracycline hydrochloride in extemporaneously compounded oral liquids.
AB  - The stability of five drugs commonly prescribed for use in oral liquids but not
      commercially available as such was studied. Bethanechol chloride 5 mg/mL,
      pyrazinamide 10 mg/mL, quinidine sulfate 10 mg/mL, rifampin 25 mg/mL, and
      tetracycline hydrochloride 25 mg/mL were each prepared in a 1:1 mixture of Ora
      Sweet and Ora-Plus (Paddock Laboratories), a 1:1 mixture of Ora-Sweet SF and Ora
      Plus, and cherry syrup and placed in 120-mL amber clear polyethylene
      terephthalate bottles. Three bottles of each liquid were stored at 5 degrees C
      and three at 25 degrees C, all in the dark. Samples were taken initially and at
      various times up to 60 days for analysis by high-performance liquid
      chromatography and assessment of appearance and odor; pH was measured. A mean of
      at least 90% of the initial drug concentration was retained for 60 days in the
      liquids containing bethanechol chloride, pyrazinamide, or quinidine sulfate and
      for 28 days in the rifampin-containing liquids and the mixture of tetracycline
      hydrochloride and Ora-Sweet-Ora-Plus at both 5 and 25 degrees C. Tetracycline
      hydrochloride concentrations of 90% or more of the initial concentration were
      retained in the liquids prepared with Ora-Sweet SF-Ora-Plus for 10 days at 5
      degrees C and 7 days at 25 degrees C and in those prepared with cherry syrup for
      7 days at 5 degrees C and 2 days at 25 degrees C. No substantial changes in the
      appearance, odor, or pH of any liquid were observed. At 5 and 25 degrees C,
      bethanechol chloride 5 mg/mL, pyrazinamide 10 mg/mL, and quinidine sulfate 10
      mg/mL were stable in three extemporaneously compounded oral liquids for 60 days
      and rifampin 25 mg/mL was stable for 28 days. The stability of tetracycline
      hydrochloride 25 mg/mL varied with the vehicle.

PMID- 9775345
TI  - Compliance issues in the treatment of HIV infection.

PMID- 9775346
TI  - Resident's perspective on pharmacist-managed drug therapy protocols.

PMID- 9775347
TI  - Indications for use of amifostine.

PMID- 9775348
TI  - Individual monitoring for internal exposure of workers replacement of ICRP
      publication 54.

PMID- 9775349
TI  - Genetics of alpha-amylases in hexaploid oat species.
AB  - The inheritance of alpha-amylases was studied in six F2 populations of hexaploid
      oats (Avena sativa, A. byzantina, A. fatua, A. sterillis) using polyacrylamide
      gel electrophoresis. A total of 22 loci was identified and described. Three main
      linkages of four or five loci each and an additional two pairs of linked loci
      were detected. It seems likely that the three main linkage groups represent
      homeologous chromosomes. Matching of alpha-amylase profiles of hexaploid
      (AACCDD), tetraploid (AACC), and diploid (AA) species was made to assign the
      linkage groups to particular subgenomes in the hexaploid oat. It was proposed
      that Linkage 1 (Amy12-Amy10-1-Amy4-Amy13-Amy11) belongs to the D-subgenome;
      Linkage 2 (Amy10-2, Amy9-Amy8-Amy6) belongs to the A-subgenome; and Linkage 3
      (Amy7-Amy3-Amy5-Amy2) belongs to the C-subgenome of the hexaploid oat. The "malt"
      and "green" alpha-amylases in hexaploid and tetraploid oats have been identified.
      Isozymes of "green" alpha-amylase were lower in electrophoretic mobility than
      other isozymes and were governed by loci assigned to the A- and D-subgenomes.

PMID- 9775350
TI  - Allelic polymorphism of histone H1.a in duck erythrocytes.

PMID- 9775351
TI  - Genetic variation in captive koalas (Phascolarctos cinereus): parentage
      determination and individual identification.
AB  - Highly repeatable randomly amplified polymorphic DNA (RAPD) markers were
      developed for parentage studies in the koala (Phascolarctos cinereus). Of the 25
      RAPD primers screened, 5 (20.0%) produced 32 repeatable polymorphic RAPD bands
      (average/primer = 6.4 +/- 4.2). A high level of polymorphism was observed for
      each group of koalas (Featherdale, 71.9%; Lone Pine, 84.4%). All 25 koalas could
      be uniquely identified using either RAPD or microsatellite markers. Of the 32
      RAPD markers generated in koalas, 25 were informative for parentage analyses.
      These RAPD markers successfully determined both parents to three offspring and a
      male parent to a fourth offspring. Paternity analysis (where the female parent is
      known) succeeded in assigning the correct male parent to seven offspring. Our
      RAPD-PCR method generates informative genetic markers that are useful for
      parentage determination and individual identification of captive koalas. This
      would provide genetic analysis to zoos and wildlife parks as a low-cost
      alternative to the more expensive microsatellite markers.

PMID- 9775352
TI  - Genetic diversity of Yunnan local pig breeds inferred from blood protein
      electrophoresis.
AB  - Protein electrophoresis was used to examine the blood protein polymorphism in
      Yunnan local pig breeds, i.e., the Saba pig, Dahe pig, and Diannan small-ear pig
      breeds. Of 38 genetic loci surveyed, 9 were found to be polymorphic. The
      percentage of polymorphic loci (P) varies from 0.1875 to 0.2121, and the mean
      individual heterozygosity (H) varies from 0.0712 to 0.1027 in three pig breeds.
      The results indicate that blood protein polymorphism in Yunnan pig breeds is
      high. Yunnan local pig breeds have a wealth of genetic diversity at the level of
      blood proteins.

PMID- 9775353
TI  - Biochemical genetic studies on wild populations of the Vicia amoena complex
      (tribe Vicieae: Fabaceae).

PMID- 9775354
TI  - Archive contributions to a molecular phylogeography of the toad Bufo calamita in
      Britain.
AB  - A complete phylogeographic analysis of any species requires sampling throughout
      its biogeographical range. In the case of the natterjack toad Bufo calamita in
      Britain, recent local extinctions have left substantial areas of its historical
      range without extant populations. We therefore obtained tissue samples of
      archived Bufo calamita from four museums in the United Kingdom. A range of
      tissues (tongue, liver, skin, lung, and larval tail) was sampled from a total of
      33 individual animals. DNA was extracted and eight polymorphic microsatellite
      loci were scored. One or more loci were amplified successfully from 27
      individuals, and sufficient data were obtained from regions with few or no
      surviving populations to supplement a phylogeographic analysis based on extant
      populations.

PMID- 9775355
TI  - The effect of oestrus and the presence of pouch young on aerobic bacteria
      isolated from the pouch of the tammar wallaby, Macropus eugenii.
AB  - Qualitative changes in the culturable, aerobic bacterial flora isolated from the
      tammar pouch have been documented over the period leading up to oestrus, at the
      time of anticipated birth and in absence and presence of pouch young of varying
      ages. In a group of 12 animals studied thirty species of aerobic bacteria were
      isolated. Twenty five species were found in pouches with no pouch young, 9 in
      pouches with young less than 3 weeks of age and 9 in pouches containing older
      animals. Gram positive organisms including Corynebacterium spp., Micrococcus spp.
      and Staphylococcus spp. were the most frequent isolates, regardless of
      reproductive status. Whilst Gram-negative rods Klebsiella pneumoniae, Pseudomonas
      aeruginosa, Enterobacter aerogenes, and Escherichia coli were found in pouches
      with and without pouch young, but not in pouches close to oestrus, at the time of
      birth or in the presence of very young animals (< 6 days). While pouches without
      pouch young displayed the greatest diversity of bacterial species, there were
      still significant numbers of bacterial species in those containing pouch young.
      Results suggest that the microbial population of the tammar pouch does not
      seriously compromise the well-being of the young animal during crucial stages of
      immunological development. The data are consistent with observations on the
      microflora of the quokka pouch but not with data from the koala.

PMID- 9775356
TI  - Comparative molecular epidemiological investigation on different bovine herpes
      viruses.
AB  - Eight Bulgarian bovine herpes viruses, two Hungarian herpes viruses 1A, 3A,
      calves isolate named Mramor, buffalo isolate 723 and two referents BHV 1 strains
      were investigated by restrictase fragment pattern analysis. Migration profile of
      viral DNA by using different restrictase enzymes Hpa I, BamH I and Hind III were
      compared. Clearly differences among two Hungarian strains, calves isolate Mramor,
      buffalo isolate 723 and 8 Bulgarian and two referents BHV 1 strain was observed.
      The strain Sartze was determined as a genital type BHV 1, whereas Ozet, Tch.voda,
      Slivnitza, B. Budinov, Ptcelarovo, Vrana and Podgumer as a respiratory type.
      Hungarian strains 1A, 3A, calves isolate Mramor and buffalo isolate 723 had
      similar migration profile as swine herpes viruses. Hybridisation between the K 22
      fragment and 8 bovine herpes viruses after Southern blotting were observed. That
      is evidence for genetic relation of these strains. Such hybridisation with
      Hungarian 1A, 3A, Mramor and buffaloes 723 strains were not observed. This fact
      allowed us to conclude that these strains are genetically different from BHV 1.

PMID- 9775357
TI  - Immunogenicity of purified lipopolysaccharide or protein-oligosaccharide
      conjugates of Pasteurella multocida type 6:B in mice.
AB  - Purified lipopolysaccharide (LPS) of Pasteurella multocida type 6:B, while toxic
      at higher doses, was protective at lower dose levels against experimentally
      induced pasteurellosis in mice. However, the observed protection was abrogated if
      such LPS was digested with proteinase K prior to use in immunisation. The O
      antigen polysaccharide side-chain (OS) of LPS did not appear to contribute to the
      observed protection as judged by the fact that immunisation of mice with purified
      OS or OS-protein conjugates, all of which were nontoxic, failed to confer
      protection against challenge with homologous virulent organisms. This was despite
      generation of significant levels of OS-specific antibodies, predominantly either
      of the IgM or IgG isotypes, in immunised mice.

PMID- 9775358
TI  - Identification and localization of a 94 kDa membrane protein found in Mycoplasma
      bovoculi strains.
AB  - Six isolates of Mycoplasma bovoculi obtained from cattle herds with bovine
      keratoconjunctivitis were analyzed by gel electrophoresis and immunoblotting
      techniques. All six strains showed similarity in their protein profiles although
      no two patterns were identical. Antigenic differences between strains were
      detected in immunoblots reacted with post-exposure calf serum. A common 94 kDa
      protein band designated p94 was detected in all six strains reacted with
      monoclonal antibody MA25.5 developed to one of the strains. The p94 was also
      recognized in these strains by the calf serum. Trypsin treatment of intact
      mycoplasma cells resulted in the removal of p94 from immunoblots reacted with MA
      or hyperimmune rabbit serum. Other trypsin-resistant antigens shared between
      strains or being strain-specific in nature were identified when trypsin-treated
      mycoplasma cells were reacted with hyperimmune rabbit serum. The p94 antigen was
      shown to be of mycoplasmal origin by radio-immunoprecipitation using the MA or
      hyperimmune rabbit serum. These studies identify the presence of a surface
      antigen (p94) on M. bovoculi membrane in all strains examined that is trypsin
      sensitive by the use of monoclonal antibody, calf serum and hyperimmune rabbit
      serum.

PMID- 9775359
TI  - Experimental infection of pigs with a thymidine kinase negative strain of
      pseudorabies virus.
AB  - Sixteen 20 day old pigs, devoid of neutralizing antibody to pseudorabies virus
      (PRV), were divided into two groups of eight, an the animals of each group were
      housed in a separate unit. In each group 6 pigs were inoculated intranasally with
      the thymidine kinase (TK-) mutant (Group 1) or the field strain of PRV (Group 2),
      each pig receiving an inoculum of 4 ml. The remaining 2 pigs in each group served
      as uninoculated controls. The only clinical sign observed in the pigs of Group 1
      was a transient febrile reaction, in the case of six pigs inoculated with the TK-
      mutant of PRV, whereas no signs of disease were seen in the uninoculated
      controls. The virus was isolated from the 6 infected pigs of the group only on
      post infection day (PID) 2, whereas it was never isolated from the controls. By
      contrast, the pigs of Group 2, had a severe clinical response and one, among
      those that were inoculated with the field strain of the PRV, died on PID 9. Virus
      was consistently isolated from all pigs of Group 2, inoculated and control. On
      PID 30 all pigs, i.e. the 8 of Group 1 and 7 of the Group 2 which survived to the
      infection, were subjected to dexamethasone (DMS) treatment. After DMS treatment
      virus was never isolated from the nasal swabbings obtained from the pigs of Group
      1, whereas it was consistently isolated from pigs of Group 2. After 30 d from the
      start of DMS treatment the pigs were killed and several tissues were collected
      from each pig for virus detection, by isolation in tissue culture and by PCR
      analysis. At necropsy no lesions were found in pigs of Group 1, whereas acute
      pneumonia and gliosis in the trigeminal ganglia were observed in pigs of Group 2.
      Virus was never isolated from any of the tissues taken from pigs of both, Group 1
      and Group 2, nevertheless sequences of PRV were detected by PCR analysis in the
      trigeminal ganglia of the pigs of both Groups.

PMID- 9775360
TI  - Effect of vaccination and the immunomodulators "bacillus of Calmette-Guerin,
      avridine and Propionibacterium acnes" on rabies in mice.
AB  - Responses of vaccination and treatment to immunomodulators against rabies in mice
      were evaluated through macrophage inhibition factor (MIF), intra-pad inoculation
      (IPI) and serum neutralization (SN) tests and by the detection of gamma
      interferon (IFN-gamma). Onco-BCG, Avridine and Propionibacterium acnes were
      administered to groups of mice. Higher survival rates were found in animals
      treated with P. acnes. Lower levels of IFN-gamma were observed in the groups of
      infected and vaccinated mice. The IPI was not effective on detecting the response
      of delayed-type hypersensitivity. Vaccine induced in the infected animals a more
      intense response to MIF reaction.

PMID- 9775361
TI  - A comparative study on certain enzymes of the granulocyte from different ruminant
      species.
AB  - In the present study the level of enzyme hydrolases (alkaline phosphatase,
      myeloperoxidase, elastase, arginase, lysozyme and beta-galactosidase) of
      polymorphonuclear cell (PMN) granules in different ruminant species and their
      release in response to activation was studied. Buffalo PMN alkaline phosphatase
      activity was higher (P < 0.01) than in PMNs of cattle and goats. Interestingly,
      myeloperoxidase was higher in cattle PMNs and least in goat PMNs (P < 0.01), a
      similar pattern was observed in the distribution of enzyme arginase. As far as
      lysozyme is concerned, its activity was significantly higher (P < 0.01) in PMNs
      of buffaloes than in the case of cattle and goat PMNs. On activation, these cells
      released MPO and elastase, in all the species studied, while lysozyme was
      secreted only in buffalo PMN cells. Activity of certain enzymes related to
      oxidant defence systems such as glutathione peroxidase and glutathione reductase
      were higher in cattle and goats compared to that in buffaloes. These observations
      are likely to have bearing on immunodefense roles played by PMNs and reflected
      differences among the ruminant species studied.

PMID- 9775362
TI  - Passive immunisation of neonatal lambs via colostrum and milk of ewes previously
      immunised with live attenuated Salmonella typhimurium protects neonatal lambs
      from experimental salmonellosis.
AB  - Lambs sucking non-immunised ewes or ewes immunised 4-5 weeks before lambing with
      live attenuated, aromatic-dependent (aroA) Salmonella typhimurium (strain CS 332)
      were challenged orally at either 2, 4 or 7 days of age with virulent S.
      typhimurium (strain CS 94) at doses ranging from 10(9) to 10(13) colony forming
      units. No lambs displayed signs of clinical salmonellosis and all survived
      challenge but those sucking immunised ewes had organisms of the challenge strain
      in their faeces for much shorter periods of time than lambs of the control ewes.
      High titres of specific antibodies were measured in colostrum and milk of
      immunised ewes in comparison with very low titres measured in samples from
      control ewes; these differences were reflected by the titres of antibodies in the
      sera of corresponding lambs. At 2 days after lambing, the major antibody isotype
      in the colostrum of immunised ewes and sera of their lambs was IgM whereas at 7
      days IgG1 was the predominant isotype. While it was clear that vaccination of
      pregnant ewes with the live attenuated vaccination conferred protection against
      experimentally-induced salmonellosis in their lambs, considerable protection was
      observed in control lambs in spite of there being very low titres of antibodies
      in the mammary secretion of their dams. The latter observation could be related
      to the presence of contain non-antibody potent bactericidal factors previously
      described in colostrum and milk.

PMID- 9775363
TI  - Multiresolution elastic image registration.
AB  - We have developed a multiscale algorithm for elastic (or molded) alignment of
      images. There is a wide array of medical applications of elastic (as opposed to
      strictly rigid) alignment: Subtraction of previous images from current ones to
      identify changes is perhaps the most obvious. We present preliminary results of
      this molding technique on a variety of images, and conclude with some closing
      remarks about this and future directions and goals of this work.

PMID- 9775364
TI  - Calculated mammographic spectra confirmed with attenuation curves for molybdenum,
      rhodium, and tungsten targets.
AB  - A model for calculating mammographic spectra independent of measured data and
      fitting parameters is presented. This model is based on first principles. Spectra
      were calculated using various target and filter combinations such as
      molybdenum/molybdenum, molybdenum/rhodium, rhodium/rhodium, and
      tungsten/aluminum. Once the spectra were calculated, attenuation curves were
      calculated and compared to measured attenuation curves. The attenuation curves
      were calculated and measured using aluminum alloy 1100 or high purity aluminum
      filtration. Percent differences were computed between the measured and calculated
      attenuation curves resulting in an average of 5.21% difference for
      tungsten/aluminum, 2.26% for molybdenum/molybdenum, 3.35% for rhodium/rhodium,
      and 3.18% for molybdenum/rhodium. Calculated spectra were also compared to
      measured spectra from the Food and Drug Administration [Fewell and Shuping,
      Handbook of Mammographic X-ray Spectra (U.S. Government Printing Office,
      Washington, D.C., 1979)] and a comparison will also be presented.

PMID- 9775365
TI  - A genetic algorithm-based method for optimizing the performance of a computer
      aided diagnosis scheme for detection of clustered microcalcifications in
      mammograms.
AB  - Computer-aided diagnosis (CAD) schemes have the potential of substantially
      increasing diagnostic accuracy in mammography by providing the advantages of
      having a second reader. Our laboratory has developed a CAD scheme for detecting
      clustered microcalcifications in digital mammograms that is being tested
      clinically at the University of Chicago Hospitals. Our CAD scheme contains a
      large number of parameters such as filter weights, threshold levels, and region
      of interest (ROI) sizes. The choice of these parameter values determines the
      overall performance of the system and thus must be carefully set. Unfortunately,
      when the number of parameters becomes large, it is very difficult to obtain the
      optimal performance, especially when the values of the parameters are correlated
      with each other. In this study, we address the problem of identifying the optimal
      overall performance by developing an automated method for the determination of
      the parameter values that maximize the performance of a mammographic CAD scheme.
      Our method utilizes a genetic algorithm to search through the possible parameter
      values, and provides the set of parameters that minimize a cost function which
      measures the performance of the scheme. Using a database of 89 digitized
      mammograms, our method demonstrated that the sensitivity of our CAD scheme can be
      increased from 80% to 87% at a false positive rate of 1.0 per image. We estimate
      the average performance of our CAD scheme on unknown cases by performing
      jackknife tests; this was previously not feasible when the parameters of the CAD
      scheme were determined in a nonautomated manner.

PMID- 9775366
TI  - Effects of lossy compression on lesion detection: predictions of the
      nonprewhitening matched filter.
AB  - The nonprewhitening matched filter (NPWMF) was used to study the effect of
      wavelet-based lossy image compression on lesion detectability. Two classes of
      images, representing lesion-present and lesion-absent cases, were generated by
      simulation techniques. The performance index, da, of the NPWMF was calculated
      from the reconstructed images of the two classes and was used as an objective
      measure for quantifying signal detectability. The effect of compression on
      detectability was analyzed by defining signal amplitude, signal size, and noise
      amplitude at a constant da. Since human observer studies directly correlate with
      the performance index da, the effect of signal parameters on compression ratios
      could be evaluated. For example, a signal with 7 pixels in diameter and an
      amplitude of 10 that was compressed at a ratio of 4.6:1, and a signal of the same
      size with an amplitude of 15 but compressed at a ratio of 24.3:1, both had a da
      of 4.1, implying identical detectability. Similar results for other combinations
      of signal and noise parameters, but at constant da, can be used to analyze the
      effect of compression on detectability without requiring human observer studies.

PMID- 9775367
TI  - Relation between radiographic mottle for double and single emulsions.
AB  - The radiographic density fluctuations produced by using dual screen-film systems
      are designated as the radiographic mottle. The density fluctuation of the
      radiographic mottle for the double emulsions at a density of the double emulsions
      consists of those for the front and back emulsions on a radiograph. However, the
      relation between the Wiener spectra of the radiographic mottle for the double and
      single emulsions had not been studied. Hence we compared the Wiener spectra of
      the radiographic mottle for the double emulsions with the sum of those for the
      front and back emulsions on the same radiographs and with the sum of those for
      the emulsions at the same densities. At all densities of more than 0.62 for lower
      spatial frequencies (< or = 1 mm-1), the Wiener spectral values of the
      radiographic mottle for the double emulsions were greater than the sum of those
      for the front and back emulsions for both comparisons on the same radiographs and
      at the same densities. In order to investigate the reason of the above phenomena,
      we separated the Wiener spectral values of the radiographic mottle for various
      densities into those of the three factors, i.e., quantum mottle, structure
      mottle, and film granularity, and performed the same comparisons as the
      radiographic mottle. Also, to explain the results for the three factors, we
      obtained the Wiener spectral values of the spatial fluctuations of the light
      exposure or the fluorescence intensity and the gradients of the characteristic
      curves of the film for the double and single emulsions of the x-ray film. As a
      result of the investigation, we found that the phenomena on the radiographic
      mottle were caused by that (1) on the same radiographs the squares of the
      gradients of the characteristic curves for the double emulsions were about 5.3
      times as great as those for the single emulsion at densities of more than 0.62 of
      the double emulsions, and (2) at the same density of more than 0.62 those were
      more than about 2.2 times as great as those for the single emulsion.

PMID- 9775368
TI  - Digital radiology using active matrix readout of amorphous selenium: geometrical
      and effective fill factors.
AB  - Flat panel self-scanned x-ray detectors using amorphous selenium (a-Se) as the
      photoconductor are being developed to replace both film/screen cassette systems
      for radiography and image intensifier (XRII)/video systems for fluoroscopy. These
      use a two-dimensional array of pixel electrodes to collect and readout the latent
      image charges formed on the photoconductor surface. The percentage of the area
      covered by the pixel electrodes (i.e., the geometrical fill factor fg) is always
      less than unity. In this paper, a novel approach is introduced to make the charge
      collection by pixel electrodes almost complete (i.e., a close to unity effective
      fill factor). The idea is to bend the electric field lines in the a-Se layer in
      such a way that image charges cannot land in the gap region between electrodes.
      This is achieved by depositing holes in the gap region, which is possible because
      there are charge traps available at the a-Se/insulator interface. The
      distribution of holes required in the gap region is calculated. Various factors
      associated with the feasibility of this approach as well as a method to deposit
      these holes are discussed. Application of the approach to the case of mammography
      is also included.

PMID- 9775369
TI  - Computerized analysis of breast lesions in three dimensions using dynamic
      magnetic-resonance imaging.
AB  - Contrast-enhanced magnetic resonance imaging (MRI) of the breast is known to
      reveal breast cancer with higher sensitivity than mammography alone. The
      specificity is, however, compromised by the observation that several benign
      masses take up contrast agent in addition to malignant lesions. The aim of this
      study is to increase the objectivity of breast cancer diagnosis in contrast
      enhanced MRI by developing automated methods for computer-aided diagnosis. Our
      database consists of 27 MR studies from 27 patients. In each study, at least four
      MR series of both breasts are obtained using FLASH three-dimensional (3D)
      acquisition at 90 s time intervals after injection of Gadopentetate dimeglumine
      (Gd-DTPA) contrast agent. Each series consists of 64 coronal slices with a
      typical thickness of 2 mm, and a pixel size of 1.25 mm. The study contains 13
      benign and 15 malignant lesions from which features are automatically extracted
      in 3D. These features include margin descriptors and radial gradient analysis as
      a function of time and space. Stepwise multiple regression is employed to obtain
      an effective subset of combined features. A final estimate of likelihood of
      malignancy is determined by linear discriminant analysis, and the performance of
      classification by round-robin testing and receiver operating characteristics
      (ROC) analysis. To assess the efficacy of 3D analysis, the study is repeated in
      two-dimensions (2D) using a representative slice through the middle of the
      lesion. In 2D and in 3D, radial gradient analysis and analysis of margin
      sharpness were found to be an effective combination to distinguish between benign
      and malignant masses (resulting area under the ROC curve: 0.96). Feature analysis
      in 3D was found to result in higher performance of lesion characterization than
      2D feature analysis for the majority of single and combined features. In
      conclusion, automated feature extraction and classification has the potential to
      complement the interpretation of radiologists in an objective, consistent, and
      accurate way.

PMID- 9775370
TI  - Review and evaluation of MRI nonuniformity corrections for brain tumor response
      measurements.
AB  - Current MRI nonuniformity correction techniques are reviewed and investigated.
      Many approaches are used to remedy this artifact, but it is not clear which
      method is the most appropriate in a given situation, as the applications have
      been with different MRI coils and different clinical applications. In this work
      four widely used nonuniformity correction techniques are investigated in order to
      assess the effect on tumor response measurements (change in tumor volume over
      time): a phantom correction method, an image smoothing technique, homomorphic
      filtering, and surface fitting approach. Six brain tumor cases with baseline and
      follow-up MRIs after treatment with varying degrees of difficulty of segmentation
      were analyzed without and with each of the nonuniformity corrections. Different
      methods give significantly different correction images, indicating that rf
      nonuniformity correction is not yet well understood. No improvement in tumor
      segmentation or in tumor growth/shrinkage assessment was achieved using any of
      the evaluated corrections.

PMID- 9775371
TI  - Automated seed localization from CT datasets of the prostate.
AB  - With the increasing utilization of permanent brachytherapy implants for treating
      carcinoma of the prostate, the importance of accurate post-treatment dose
      calculation also increases for assessing patient outcome and planning future
      treatments. An automatic method for seed localization of permanent brachytherapy
      implants, using CT datasets of the prostate, has been developed and tested on a
      phantom using an actual patient planned seed distribution. This method was also
      compared to results with the three-film technique for three patient datasets. The
      automatic method is as accurate or more accurate than the three film technique
      for 1 mm, 3 mm, and 5 mm contiguous CT slices, and eliminates the inter- and
      intra-observer variability of the manual methods. The automated method improves
      the localization of brachytherapy seeds while reducing the time required for the
      user to input information, and is demonstrated to be less operator dependent,
      less time consuming, and potentially more accurate than the three-film technique.

PMID- 9775372
TI  - Monte Carlo calculation of single-beam dose profiles used in a gamma knife
      treatment planning system.
AB  - The accuracy of single-beam dose profiles used in the algorithm of the Gamma
      Knife treatment planning system (Leksell GammaPlan) is verified. EGS4 Monte Carlo
      calculation was employed to calculate the dose distributions of single-beams in a
      spherical water phantom with diameter 160 mm. The beams were directed to the
      center of the phantom. Collimators of 4, 8, 14, and 18 mm sizes were studied. The
      single-beam dose profiles provided by Elekta (Manufacturer of Leksell Gamma
      Knife) were excellently consistent with the results of Monte Carlo for the 4, 14,
      and 18 mm collimators. The maximum discrepancy was less than 3% at all radial
      distances. For the 8 mm collimator, the maximum discrepancy was 8% in the
      relative dose in the radial distance range from 4.3 mm to 5.2 mm. Excellent
      agreement in dose profiles along x, y, and z axes for all collimator helmets by
      summing over all 201 sources was observed between the cases using the default
      single-beam dose profiles and the calculated Monte Carlo results, except for the
      8 mm collimator helmet along z axis. Such difference may however be too small to
      give a clinical significance.

PMID- 9775373
TI  - Beam characteristics of a retrofitted double-focused multileaf collimator.
AB  - Multileaf collimators (MLCs) are generally believed to be convenient and cost
      effective tools for intensity modulation and conformal therapy. They are becoming
      a standard feature on new accelerators; however, the older units can be
      retrofitted with modern MLCs. Before such a unit can be clinically used, the beam
      characteristics must be verified. In this study the beam characteristics of a
      Siemens double-focused MLC retrofitted to an MD2 linear accelerator are
      presented. The head leakage along with inter- and intra-leaf radiation
      transmission were measured using film. The collimator (Sc), phantom (Sp), total
      (Scp) scatter factors, central axis depth dose, beam profiles for off-axis
      ratios, penumbra, and surface dose were evaluated for square, rectangular, and
      irregularly shaped fields. The maximum head leakage was estimated to be < 0.05%
      in any plane at a distance of 1 m and maximum transmission through the MLC leaves
      was estimated to be < 1.4% and < 1.1% for the 10 MV and 6 MV beams, respectively.
      The maximum differences between pre- and post-MLC installation data for the Sc
      and Scp were < or = 0.7% and < or = 1.4%, respectively. Similarly, the percent
      depth dose data for all fields and both beam energies were within 1.5% of the
      original data. The beam profiles measured at various depths were also in
      agreement with those of the pre-MLC installation data. The measured beam penumbra
      (20%-80%) showed a range of 7.8 mm-11.0 mm for the 6 MV and 8.4 mm-11.1 mm for
      the 10 MV beams from smallest to largest fields. These ranges differ by less than
      a millimeter from those of the old data. The surface dose measurements were
      slightly lower than the conventional jaw values suggesting that MLC does not
      produce significant electron contamination. It is concluded that the retrofitted
      MLC maintains the integrity of the original beam and may provide a cost-effective
      conformal therapy.

PMID- 9775374
TI  - A generalized film technique for the verification of vertex fields used in the
      treatment of brain tumors.
AB  - With the availability of commercial three-dimensional (3D)-treatment planning
      systems, more and more treatment plans call for the use of noncoplanar conformal
      beams for the treatment of brain tumors. However, techniques for the verification
      of many noncoplaner beams, such as vertex fields which involve any combination of
      gantry, collimator, and table angles, do not exist. The purpose of this work is
      to report on the results of an algorithm and a technique that have been developed
      for the verification of noncoplanar vertex fields used in the treatment of brain
      tumors. This technique is applicable to any geometric orientation of the beam,
      i.e., a beam orientation that consists of any combination of gantry, table, and
      collimator rotations. The method consists of superimposing a central plane image
      of a correctly magnified vertex field on a lateral or oblique field port film. To
      achieve this, the 3D coordinates of the projection of the isocenter onto the film
      for lateral (or oblique) as well as the vertex fields are determined and then
      appropriately matched. Coordinate transformation equations have been developed
      that enable this matching precisely. A film holder has been designed such that a
      film cassette can be secured rigidly along the side rails of the treatment table.
      The technique for taking a patient treatment setup verification film consists of
      two steps. In the first step, the gantry, table, and collimator angles for the
      lateral (or oblique) field are set and the usual double exposures are made; the
      first exposure corresponds to that of the treatment portal with the isocenter
      clearly identified and the second one a larger radiation field so that the
      peripheral anatomy is visible on the film. In the next step, the gantry, table,
      and collimator angles are positioned for the vertex field and the table is moved
      laterally and vertically and the film longitudinally to a position that will
      enable precise matching of the isocenter on the film. A third exposure is then
      taken with the vertex portal. What is seen on the film is a superposition of a
      central plane image of the vertex field onto the image of the lateral or oblique
      field. This technique has been used on 60 patients treated with noncoplanar
      fields for brain tumors. In all of these cases, the coincidence of the projection
      of the isocenter for the lateral (or oblique) and the vertex fields was found to
      be within 3 mm.

PMID- 9775375
TI  - A generalized solution for the calculation of in-air output factors in irregular
      fields.
AB  - Three major contributors of scatter radiation to the in-air output of a medical
      linear accelerator are the flattening filter, wedge, and tertiary collimator.
      These were considered separately in the development of an algorithm to be used to
      set up an in-air output factor calculation formalism for open and wedge fields of
      irregular shape. A detector's eye view (DEV) field defined at the source plane
      was used to account for the effects of collimator exchange and the partial
      blockage of the flattening filter by the tertiary collimator in the determination
      of head scatter. An irregular field determined at the source plane by a DEV was
      segmented and mapped back into the detector plane by a field-mapping method.
      Field mapping was performed by using a geometric conversion factor and equivalent
      field relationships for head scatter. The scatter contribution of each segmented
      equivalent field at the detector plane was summed by Clarkson integration. The
      same methodology was applied for determining both tertiary collimator and wedge
      scatter contribution. However, the field size that determined the amount of
      scatter contribution was not the same for each component. For tertiary collimator
      scatter and external wedge scatter, a field projected to the detector plane was
      used directly. Comparisons of calculated and measured values for in-air output
      factors showed good agreement for both open and external wedge fields. This
      algorithm can also be used for multileaf collimator (MLC) fields irrespective of
      the position of the MLC (i.e., whether the MLC replaces one secondary collimator
      or is used as a tertiary collimator). The measurement and parameterization of
      tertiary collimator scatter is necessary to account for its contribution to the
      in-air output. Because a source-plane field is mapped into the detector plane, no
      additional dosimetric data acquisition is necessary for the calculation of head
      scatter.

PMID- 9775376
TI  - Forward and adjoint methods for radiotherapy planning.
AB  - The sensitivity theory developed for nuclear engineering applications is applied
      to radiotherapy planning. After emphasizing the mathematical equivalence of
      solving the Boltzmann equation in forward and adjoint spaces both mathematical
      approaches are implemented to calculate the sensitivities of the dose
      distributions in a mathematical phantom to changes in the source of radiation.
      The tagging of the functionals of the radiation field with the origin of the
      source (forward or adjoint) makes possible the calculation of the sensitivity of
      the dose to the position, angular distribution, intensity, and spectra of the
      source, in a very efficient way by using present day available codes and
      hardware. There is then a potential for a new, accurate and potentially faster
      method that does not rely on a trial and error methodology.

PMID- 9775377
TI  - Effects of changes in stopping-power ratios with field size on electron beam
      relative output factors.
AB  - Stopping-power ratios are a function of field size and vary with accelerators. To
      investigate how these variations affect relative output factor measurements made
      using ion chambers for electron beams, especially for small fields,
      (L/rho)air(water) is calculated using the Monte Carlo technique for different
      field sizes, beam energies, and accelerators and is compared to the data in TG-21
      or TG-25, which are for mono-energetic broad beams. For very small field sizes
      defined by cutouts, if the change in (L/rho)air(water) with dmax is ignored
      (i.e., TG-25 is not carefully followed), there is an overestimate of relative
      output factors by up to 3%. Ignoring the field-size effect on stopping-power
      ratio adds an additional overestimate of up to one-half percent, and using mono
      energetic stopping-power ratio data instead of realistic beam data gives another
      error, but in the opposite direction, of up to 0.7%. Due to the cancellation of
      these latter two errors, following TG-25 with (L/rho)air(water) data for broad
      mono-energetic beams will give the correct answer for the ROF measurement within
      0.4% compared to using (L/rho)air(water) data for which the field-size effect is
      considered for realistic electron beams.

PMID- 9775378
TI  - In-phantom dosimetry and spectrometry of photoneutrons from an 18 MV linear
      accelerator.
AB  - A combination of three superheated drop detectors with different neutron energy
      responses was developed to evaluate dose-equivalent and energy distributions of
      photoneutrons in a phantom irradiated by radiotherapy high-energy x-ray beams.
      One of the three detectors measures the total neutron dose equivalent and the
      other two measure the contributions from fast neutrons above 1 and 5.5 MeV,
      respectively. In order to test the new method, the neutron field produced by the
      10 cm X 10 cm x-ray beam of an 18 MV radiotherapy accelerator was studied.
      Measurements were performed inside a tissue-equivalent liquid phantom, at depths
      of 1, 5, 10 and 15 cm and at lateral distances of 0, 10, and 20 cm from the
      central axis. These data were used to calculate the average integral dose to the
      radiotherapy patient from direct neutrons as well as from neutrons transmitted
      through the accelerator head. The characteristics of the dosimeters were
      confirmed by results in excellent agreement with those of prior studies. Track
      etch detectors were also used and provided an independent verification of the
      validity of this new technique. Within the primary beam, we measured a neutron
      entrance dose equivalent of 4.5 mSv per Gy of photons. It was observed that fast
      neutrons above 1 MeV deliver most of the total neutron dose along the beam axis.
      Their relative contribution increases with depth, from about 60% at the entrance
      to over 90% at a depth of 10 cm. Thus, the average energy increases with depth in
      the phantom as neutron spectra harden.

PMID- 9775379
TI  - Designing accelerator-based epithermal neutron beams for boron neutron capture
      therapy.
AB  - The 7Li(p,n)7Be reaction has been investigated as an accelerator-driven neutron
      source for proton energies between 2.1 and 2.6 MeV. Epithermal neutron beams
      shaped by three moderator materials, Al/AlF3, 7LiF, and D2O, have been analyzed
      and their usefulness for boron neutron capture therapy (BNCT) treatments
      evaluated. Radiation transport through the moderator assembly has been simulated
      with the Monte Carlo N-particle code (MCNP). Fluence and dose distributions in a
      head phantom were calculated using BNCT treatment planning software. Depth-dose
      distributions and treatment times were studied as a function of proton beam
      energy and moderator thickness. It was found that an accelerator-based neutron
      source with Al/AlF3 or 7LiF as moderator material can produce depth-dose
      distributions superior to those calculated for a previously published neutron
      beam design for the Brookhaven Medical Research Reactor, achieving up to
      approximately 50% higher doses near the midline of the brain. For a single beam
      treatment, a proton beam current of 20 mA, and a 7LiF moderator, the treatment
      time was estimated to be about 40 min. The tumor dose deposited at a depth of 8
      cm was calculated to be about 21 Gy-Eq.

PMID- 9775380
TI  - Phantoms with 10BF3 detectors for boron neutron capture therapy applications.
AB  - Two acrylic cube phantoms have been constructed for BNCT applications that allow
      the depth distribution of neutrons to be measured with miniature 10BF3 detectors
      in 0.5-cm steps beginning at 1-cm depth. Sizes and weights of the cubes are 14
      cm, 3.230 kg, and 11 cm, 1.567 kg. Tests were made with the epithermal neutron
      beam from the patient treatment port of the Brookhaven Medical Research Reactor.
      Thermal neutron depth profiles were measured with a bare 10BF3 detector at a
      reactor power of 50 W, and Cd-covered detector profiles were measured at a
      reactor power of 1 kW. The resulting plots of counting rate versus depth
      illustrate the dependence of neutron moderation on the size of the phantom. But
      more importantly the data can serve as benchmarks for testing the thermal and
      epithermal neutron profiles obtained with accelerator-based BNCT facilities. Such
      tests could be made with these phantoms at power levels about five orders of
      magnitude lower than that required for the treatment of patients with brain
      tumors.

PMID- 9775381
TI  - A tilt and roll device for automated correction of rotational setup errors.
AB  - A tilt and roll device has been developed to add two additional degrees of
      freedom to an existing treatment table. This device allows computer-controlled
      rotational motion about the inferior-superior and left-right patient axes. The
      tilt and roll device comprises three supports between the tabletop and base. An
      automotive type universal joint welded to the end of a steel pipe supports the
      center of the table. Two computer-controlled linear electric actuators utilizing
      high accuracy stepping motors support the foot of table and control the tilt and
      roll of the tabletop. The current system meets or exceeds all pre-design
      specifications for precision, weight capacity, rigidity, and range of motion.

PMID- 9775382
TI  - Optical CT reconstruction of 3D dose distributions using the ferrous-benzoic
      xylenol (FBX) gel dosimeter.
AB  - In recent years, magnetic-resonance imaging of gelatin doped with the Fricke
      solution has been applied to the direct measurement of three-dimensional (3D)
      radiation dose distributions. However, the 3D dose distribution can also be
      imaged more economically and efficiently using the method of optical absorption
      computed tomography. This is accomplished by first preparing a gelatin matrix
      containing a radiochromic dye and mapping the radiation-induced local change in
      the optical absorption coefficient. Ferrous-Benzoic-Xylenol (FBX) was the dye of
      choice for this investigation. The complex formed by Fe3+ and xylenol orange
      exhibits a linear change in optical attenuation (cm-1) with radiation dose in the
      range between 0 and 1000 cGy, and the local concentration of this complex can be
      probed using a green laser light (lambda = 543.5 nm). An optical computed
      tomography (CT) scanner was constructed analogous to a first-generation x-ray CT
      scanner, using a He-Ne laser, photodiodes, and rotation-translation stages
      controlled by a personal computer. The optical CT scanner itself can reconstruct
      attenuation coefficients to a baseline accuracy of < 2% while yielding dose
      images accurate to within 5% when other uncertainties are taken into account.
      Optical tomography is complicated by the reflection and refraction of light rays
      in the phantom materials, producing a blind spot in the transmission profiles
      which, results in a significant dose artifact in the reconstructed images. In
      this report we develop corrections used to reduce this artifact and yield
      accurate dosimetric maps. We also report the chemical reaction kinetics, the dose
      sensitivity and spatial resolution (< 1 mm3) obtained by optical absorption
      computed tomography. The article concludes with sample dose distributions
      produced by "cross-field" 6 MV x-ray beams, including a radiosurgery example.

PMID- 9775383
TI  - Ion recombination and polarity effect of ionization chambers in kilovoltage x-ray
      exposure measurements.
AB  - Exposure measurements with ionization chambers are dependent on the correction
      factors related to the beam energy (ke), temperature and pressure (ktp),
      ionization recombination (Pion), and polarity (kpol) effects. In this work, six
      different chambers commonly used in diagnostic radiology were investigated for
      the Pion and kpol at various exposure rates by changing the tube voltage, beam
      current, exposure time, and distance. A special triaxial connector was used to
      connect chambers to an electrometer capable of measuring positive and negative
      polarity and 150 V and 300 V electrode potentials to measure the kpol and Pion,
      respectively. A mammography unit (24-35 kVp) and a diagnostic x-ray unit (60-125
      kVp) were used. Results indicate that the magnitude of the Pion is linearly
      dependent on kVp for large volume (> 150 cm3) chambers and independent for small
      volume (< or = 150 cm3) chambers. In general, Pion is higher at higher exposures
      (increasing kVp, mAs, and decreasing distance); however, kpol is independent of
      exposure rate and kVp, but strongly depends on the sensitive volume of an ion
      chamber. Pion and kpol vary between 1-48% and 1-16%, respectively, among various
      chambers and exposure conditions. Chambers with larger volumes have higher values
      of Pion and kpol. The desired accuracy of +/- 5% in exposure measurements might
      not be feasible unless both the polarity and recombination effects are known and
      accounted accurately.

PMID- 9775384
TI  - Comment on "Attenuation characteristics of a new compensator material: Thermo
      Shield for high energy electron and photon beams" [Med. Phys. 25, 485-487
      (1998)].

PMID- 9775385
TI  - Tenth International Genome Sequencing and Analysis Conference. Miami Beach,
      Florida, USA. September 17-20, 1998. Proceedings and abstracts.

PMID- 9775386
TI  - The CorA magnesium transporter gene family.
AB  - The CorA transport system is the primary Mg2+ influx system of Salmonella
      typhimurium and Escherichia coli. The CorA protein has no homology to any other
      known family of proteins. It has an unusual membrane topology, with a large,
      soluble, highly charged periplasmic N-terminal domain with three transmembrane
      segments in a shorter, hydrophobic C-terminal domain. Previous phenotypic and
      molecular data had suggested that this transport system was widespread in the
      Bacteria. In this report we show that CorA is virtually ubiquitous in the
      Bacteria and Archaea, forming a distinct family of transport proteins. Genomic
      sequences to date have revealed at least 22 members of the CorA family in the
      Bacteria and the Archaea, with 6 more distant members in the yeasts. Only three
      of the smallest bacterial genomes lack a CorA homologue. Strikingly, phylogenetic
      analysis does not show clustering by related species or even within kingdom.
      Several species of Bacteria contain two or even three CorA paralogues. Within
      species, these paralogues are not closely related, however, and we suggest that
      they might have distinct transport functions. A multiple alignment suggests three
      extended consensus regions within the N-terminal soluble domain of CorA, which is
      predicted to be virtually all alpha-helical. A fourth consensus region includes
      the last 20 residues of the soluble domain and continues through the entire
      membrane domain. The first half of this last consensus domain may form an
      amphipathic alpha-helix that extends from the soluble domain into the first
      transmembrane segment. The degree of charge in the first transmembrane segment is
      quite variable, and we suggest that this transport family may include members
      with only two rather than three transmembrane segments. If so, this would place
      the N-terminal soluble domain on different sides of the membrane in different
      members of the family. We suggest that the CorA Mg2+ transport system forms the
      major Mg2+ uptake system in the Bacteria and Archaea but that some family members
      may have a function other than Mg2+ transport.

PMID- 9775387
TI  - Assignment of folds for proteins of unknown function in three microbial genomes.
AB  - Analysis of DNA sequences of several microbial genomes has revealed that a large
      fraction of predicted coding regions has no known protein function. Information
      about the three-dimensional folds of these proteins may provide insight into
      their possible functions. To predict the folds for protein sequences with little
      or no homology to proteins of known function, we used computational neural
      networks trained on the database of proteins with known three-dimensional
      structures. Global descriptions of protein sequences based on physical and
      structural properties of the constituent amino acids were used as inputs for
      neural networks. Of the 131, 498, and 868 protein sequences of unknown function
      from Mycoplasma genitalium, Haemophilus influenzae, and Methanococcus jannaschii
      (Fleischmann et al. 1995), we have made high-confidence fold assignments for 4,
      10, and 19 sequences, respectively.

PMID- 9775388
TI  - Constructing multigenome views of whole microbial genomes.
AB  - We have designed and implemented a system to carry out cross-genome comparisons
      of open reading frames (ORFs) from multiple genomes. This implementation includes
      a genome profiling system that allows us to explore pairwise comparisons at
      different levels of match similarity and ask biologically motivated queries
      involving number and identity of ORFs, their function, functional category,
      distribution in genomes or in biological domains, and statistics on their matches
      and match families. This analysis required precise definition of new
      classification terms and concepts. We define the terms genomic signature, summary
      signature, biologic domain signature, domain class, match level, match family,
      and extended match family, then use these terms to define concepts, including
      genomically universal proteins and proteins characteristics of sets of genomes.
      We initiate an analysis based on automated FASTA (Pearson, 1996) comparison of
      22,419 conceptually translated protein sequences from nine microbial genomes.

PMID- 9775389
TI  - Meeting summary. Computational genomics I.

PMID- 9775390
TI  - The Dorothy Russell Memorial Lecture. The molecular and cellular sequelae of
      experimental traumatic brain injury: pathogenetic mechanisms.
AB  - The mechanisms underlying secondary or delayed cell death following traumatic
      brain injury (TBI) are poorly understood. Recent evidence from experimental
      models of TBI suggest that diffuse and widespread neuronal damage and loss is
      progressive and prolonged for months to years after the initial insult in
      selectively vulnerable regions of the cortex, hippocampus, thalamus, striatum,
      and subcortical nuclei. The development of new neuropathological and molecular
      techniques has generated new insights into the cellular and molecular sequelae of
      brain trauma. This paper will review the literature suggesting that alterations
      in intracellular calcium with resulting changes in gene expression, activation of
      reactive oxygen species (ROS), activation of intracellular proteases (calpains),
      expression of neurotrophic factors, and activation of cell death genes
      (apoptosis) may play a role in mediating delayed cell death after trauma. Recent
      data suggesting that TBI should be considered as both an inflammatory and/or a
      neurodegenerative disease is also presented. Further research concerning the
      complex molecular and neuropathological cascades following brain trauma should be
      conducted, as novel therapeutic strategies continue to be developed.

PMID- 9775391
TI  - Why do we remember Dorothy Russell?
AB  - Dorothy Russell (1985-1983), one of the leading figures in the brief history of
      British neuropathology, is remembered by the Society in a biennial Memorial
      Lecture. So rapid is progress in the Neurosciences and so short our memories,
      that for a younger generation of neuropathologists she is probably no more than a
      name associated with a large recently revised textbook on brain tumours. However,
      together with Godwin Greenfield, Dorothy Russell had a profound and lasting
      influence on the development and practice of Neuropathology throughout the world.

PMID- 9775392
TI  - NF-kB immunoreactivity is observed in association with beta A4 diffuse plaques in
      patients with Alzheimer's disease.
AB  - Transcription factor NF-kB is widely expressed in the nervous system and,
      particularly, in synaptic terminals. Increased NF-kB expression in synaptosomes
      has been observed as a result of activity, and beta A4 deposition. In the present
      study we have examined NF-kB immunoreactivity, by means of NF-kB p65
      immunohistochemistry, in the brains of seven patients with Alzheimer's disease,
      two patients with Creutzfeldt-Jakob disease associated with PrP amyloid
      deposition, and seven age-matched controls. Our purpose was to examine possible
      NF-kB induction associated to beta A4 or PrP deposition in these diseases.
      Punctate NF-kB immunoreactivity was constantly found in the neuropil of diffuse
      beta A4 deposits but not in dystrophic neurites of senile plaques. In addition,
      NF-kB immunoreactivity was found in the nuclei of neurons, but not in the nuclei
      of reactive astrocytes, in the vicinity of diffuse plaques, thus suggesting NF-kB
      translocation to the nucleus. Finally, a few neurons with neurofibrillary
      degeneration showed increased cytoplasmic NF-kB immunoreactivity probably
      secondary to abnormal compartmentation or impaired transport of NF-kB. No similar
      modifications in NF-kB immunoreactivity were observed in association with PrP
      deposits in patients with Creutzfeldt-Jakob disease. Since it has been suggested
      that the presence of NF-kB in synapses may indicate the existence of a new
      pathway of gene transcription, the present results support the concept that this
      pathway may be activated by the deposition of beta A4 in diffuse plaques in
      Alzheimer's disease.

PMID- 9775393
TI  - Distribution of interleukin-1-immunoreactive microglia in cerebral cortical
      layers: implications for neuritic plaque formation in Alzheimer's disease.
AB  - Activated microglia overexpressing interleukin-1 (IL-1) are prominent
      neuropathological features of Alzheimer's disease. We used computerized image
      analysis to determine the number of IL-1 alpha-immunoreactive (IL-1 alpha +)
      microglia in cytoarchitectonic layers of parahippocampal gyrus (Brodmann's area
      28) of Alzheimer and control patients. For cortical layers I and II, the numbers
      of IL-1 alpha + microglia were similar in Alzheimer and control patients. For
      layers III-VI, the numbers of IL-1 alpha + microglia were higher than that seen
      in layers I-II for both Alzheimer and control patients. Moreover, for layers III
      VI, the number of IL-1 alpha + microglia in Alzheimer patients was significantly
      greater than that in control patients (relative Alzheimer values of threefold for
      layer III-V and twofold for layer VI; P < 0.05 in each case). The cortical
      laminar distribution of IL-1 alpha + microglia in Alzheimer patients correlated
      with the cortical laminar distribution of beta-amyloid precursor protein
      immunoreactive (beta-APP+) neuritic plaques found in Alzheimer patients (r =
      0.99, P < 0.005). Moreover, the cortical laminar distribution of IL-1 alpha +
      microglia in control patients also correlated with the cortical laminar
      distribution of beta-APP+ neuritic plaques found in Alzheimer patients (r = 0.91,
      P < 0.05). These correlations suggest that pre-existing laminar distribution
      patterns of IL-1 alpha + microglia (i.e. that seen in control patients) are
      important in determining the observed laminar distribution of beta-APP+ neuritic
      plaques in Alzheimer patients. These findings provide further support for our
      hypothesis that IL-1 is a key driving force in neuritic plaque formation in
      Alzheimer's disease.

PMID- 9775394
TI  - Differential expression of transforming growth factor-beta isoforms in human
      prion diseases.
AB  - To examine the involvement of transforming growth factor-beta (TGF-beta) in the
      pathogenesis of prion diseases, immunohistochemical studies on both TGF-beta
      isoforms (beta 1, beta 2 and beta 3) and TGF-beta receptor type II (TGF-beta RII)
      were performed on the cerebral neocortices of 20 cases with human prion diseases,
      three cases with Alzheimer's disease, and five control cases. TGF-beta 2
      immunoreactivity was thus detected in most neurons and astrocytes in all observed
      cases of prion disease. TGF-beta 3 immunoreactivity in the astrocytes and TGF
      beta RII in the neurons were also detected in 17 of 20 cases with prion diseases.
      These immunoreactivities had increased markedly regarding the intensity and the
      number of positive cells in comparison to the control cases, but they were
      indistinguishable from those observed in Alzheimer's disease cases. In contrast,
      the TGF-beta 1 immunostaining did not show any apparent difference. Among the
      cases with prion diseases, however, no significant correlation was revealed
      between the immunohistochemical results and the clinical and pathological
      features. The results showed that TGF-beta isoforms thus appear to be
      differentially involved in the pathogenesis of prion diseases in a similar manner
      to that of Alzheimer's disease. Furthermore, two cases of prion disease in which
      pathological findings were free from astrogliosis and neuronal cell degeneration
      in the cerebral cortices also showed an increased immunoreactivity for TGF-beta
      2. Thus, this result suggests that TGF-beta 2 may be involved in the early stages
      of neuronal cell degeneration in prion diseases.

PMID- 9775395
TI  - Differential expression of MHC class II molecules by microglia and neoplastic
      astroglia: relevance for the escape of astrocytoma cells from immune
      surveillance.
AB  - There is increasing evidence that microglia serve as antigen presenters in the
      human CNS. Although the occurrence of MHC class II immunoreactive cells has been
      reported in astrocytic gliomas, the relative contribution of microglia to this
      cell population has not been studied in detail. Using computer-assisted image
      analysis, we have investigated the expression of MHC class II molecules and of
      the microglia/macrophage markers Ki-MIP, RCA-1, KP1 and iba1, in 97 astrocytic
      gliomas comprising all WHO grades to answer the question whether there is a
      correlation between tumour grade and the number of MHC class II positive
      microglia/macrophage profiles. Microglia expressing MHC class II were common in
      astrocytomas and anaplastic astrocytomas but rare in pilocytic tumours although
      there was significant variation within each group. MHC class II immunoreactivity
      was reduced in highly cellular areas of glioblastomas where large numbers of
      cells expressing macrophage markers were still present. Thus, there was no simple
      relationship between tumour grade and microglial/macrophage MHC class II
      expression. In addition, up to 55% of astrocytic gliomas contained MHC class II
      immunoreactive tumour cells. Microglia but not tumour cells were found to express
      the BB1/B7 costimulator. We conclude that microglia in astrocytic gliomas are
      well equipped to function as antigen presenting cells. Yet, neoplastic astroglia
      appear to acquire the capacity to downregulate microglial MHC class II expression
      and, at the same time, may induce T-cell clonal anergy through aberrant
      expression of MHC class II molecules.

PMID- 9775396
TI  - Expression of neuronal markers in oligodendrogliomas: an immunohistochemical
      study.
AB  - The oligodendroglioma has been considered to be a tumour showing oligodendrocyte
      differentiation, but studies of the expression of oligodendrocyte markers have
      not conclusively demonstrated this and the pattern of differentiation of this
      tumour remains uncertain. Recent studies have suggested that some
      oligodendrogliomas may show neuronal differentiation. The aim of this study was
      to determine whether there was evidence of neuronal differentiation in a series
      of oligodendrogliomas, and, if so, to determine whether this identified a
      biologically or clinically distinct group. Immunohistochemistry was carried out
      on paraffin sections using antibodies to synaptophysin, phosphorylated and non
      phosphorylated neurofilament proteins. An archival series of 32
      oligodendrogliomas had been previously characterized for histological features,
      histological grade, Ki-67 labelling index, apoptosis index and prognosis. Six per
      cent of tumours showed expression of synaptophysin. Thirty-one per cent of cases
      showed expression of neurofilament proteins with an antibody to non
      phosphorylated epitopes, but no cases were positive with antibodies to
      phosphorylated neurofilament epitopes. Tumours showing expression of neuronal
      markers did not show a difference in the distribution of histological grade or
      GFAP expression from those which did not express these markers, and there was no
      difference in labelling indices or prognosis between the two groups. In
      conclusion, a subset of oligodendrogliomas showed expression of neuronal lineage
      markers; this is discussed in relation to histogenesis and differential
      diagnosis. The expression of such markers did not identify a biologically or
      clinically distinct subgroup.

PMID- 9775397
TI  - Matrix metalloproteinases MMP-2 and MMP-9 in denervated muscle and injured nerve.
AB  - Nerve crush or axotomy results in a transient or longterm denervation accompanied
      by remodelling in nerve, muscle and neuromuscular junctions. These changes
      include an increased turnover of several extracellular matrix molecules and
      proliferation of Schwann cells in injured nerves. Given the role of matrix
      degrading metalloproteinases MMP-2 and MMP-9 (gelatinases-type IV collagenases)
      in extracellular matrix remodelling, we investigated their regulation and
      activation in denervated muscles and injured nerves in mice. For this,
      immunofluorescence using MMP-2 and MMP-9 antibodies was carried concomitantly
      with gelatin zymography and quantification of gelatinase activity using [3H]
      gelatin substrate. Results show that in normal mouse muscles MMP-2 and MMP-9 are
      localized at the neuromuscular junctions, in Schwann cells and the perineurium of
      the intramuscular nerves. In denervated mouse muscles, MMP-2 immunolabelling
      persists at the neuromuscular junctions but decreases in the nerves whereas MMP-9
      immunolabelling persists at the neuromuscular junctions but is enhanced in
      degenerated intramuscular nerves. Denervated muscles did not show any significant
      change of gelatinolytic activity or expression pattern, while injured nerves
      exhibited a transient increase of MMP-9 and activation of MMP-2. In conclusion,
      this study demonstrates that MMP-2 and MMP-9 are expressed at mouse neuromuscular
      junctions and that their localization and expression pattern appear not to be
      modified by denervation. Their modulation in injured nerves suggests they are
      involved in axonal degeneration and regeneration.

PMID- 9775398
TI  - Identification of glial cell proliferation in early multiple sclerosis lesions.
AB  - Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous
      system which leads to destruction of myelin sheaths. The patterns of cell
      proliferation in the early course of the disease are largely unknown. The present
      study used immunohistochemical identification of proliferating glial cells in
      stereotactic brain biopsy material of eight patients with early chronic MS.
      Double-labelling with the proliferation marker MIB-1 detected proliferating
      oligodendrocytes (MOG), astrocytes (GFAP) and microglia/macrophages (Ki-M1P). The
      majority of proliferating cells were macrophages/microglia when compared with
      oligodendrocytes (P > 0.005) or astrocytes (P > 0.0005); only a minor proportion
      of microglia/macrophages, however, proliferated in situ. Astrocytic and
      oligodendroglial proliferation was sparse to absent and showed significant
      variations between different patients. There were statistically significant
      differences when comparing the amount of proliferation between lesions of
      different demyelinating activity: highest numbers of proliferating cells were
      found in early active lesions compared with demyelinated and early remyelinated
      lesions (P > 0.05) or the periplaque white matter (P > 0.01). MOG-positive
      oligodendrocytes proliferated occasionally in the early stages of lesion
      formation; this proliferation occurred in four cases but was independent of the
      stage of the disease. Since MOG is expressed by mature oligodendrocytes, and not
      by immature precursors, this might suggest a potential role for the proliferation
      of mature surviving oligodendrocytes with subsequent remyelination.

PMID- 9775399
TI  - Non-rabies Lyssavirus human encephalitis from fruit bats: Australian bat
      Lyssavirus (pteropid Lyssavirus) infection.
AB  - A 39-year-old woman died of encephalitis a few weeks after being scratched by
      fruit bats. Autopsy disclosed meningoencephalomyelitis, and revealed neuronal
      intracytoplasmic inclusions which had similarities to Negri bodies of rabies.
      Laboratory investigations detected a Lyssavirus type previously identified only
      in fruit bats. This appears to be the first human case of encephalitis due to
      this Lyssavirus type.

PMID- 9775400
TI  - Chronic ethanol consumption: from neuroadaptation to neurodegeneration.
AB  - In this review first we evaluate evidence on the role of the neurobiological
      alterations induced by chronic ethanol consumption in the development of ethanol
      tolerance, dependence and withdrawal. Secondly, we describe the neuropathological
      consequences of chronic ethanol on cognitive functions and on brain structures.
      Chronic alcohol consumption can induce alterations in the function and morphology
      of most if not all brain systems and structures. While tolerance mechanisms are
      unlikely to contribute to the neuroadaptive changes associated with ethanol
      dependence, it is otherwise clear that repeated high, intoxicating doses of
      ethanol trigger those neuroadaptive processes that lead to dependence and
      contribute to the manifestation of the abstinence syndrome upon withdrawal. An
      unbalance between inhibitory and excitatory neurotransmission is the most
      prominent neuroadaptive process induced by chronic ethanol consumption. Due to
      the diffuse glutamatergic innervation to all brain structures, the neuroadaptive
      alterations in excitatory neurotransmission can affect the function of most if
      not all of neurotransmitter systems. The expression of the withdrawal syndrome is
      the major causal factor for the onset and development of the neuropathological
      alterations. This suggests a link between the neuroadaptive mechanisms underlying
      the development of ethanol dependence and those underlying the functional and
      structural alterations induced by chronic ethanol. In animals and humans,
      specific alterations occur in the function and morphology of the diencephalon,
      medial temporal lobe structures, basal forebrain, frontal cortex and cerebellum,
      while other subcortical structures, such as the caudate nucleus, seem to be
      relatively spared. The neuropathological alterations in the function of
      mesencephalic and cortical structures are correlated with impairments in
      cognitive processes. In the brain of alcoholics, the prefrontal cortex and its
      subterritories seem particularly vulnerable to chronic ethanol, whether
      Korsakoff's syndrome is present or not. Due to the role of these cortical
      structures in cognitive functions and in the control of motivated behavior,
      functional alterations in this brain area may play an important role in the onset
      and development of alcoholism.

PMID- 9775401
TI  - Control of abdominal muscles.
AB  - Abdominal muscles serve many roles; in addition to breathing, especially at
      higher levels of chemical drive or at increased end-expiratory lung volumes, they
      are responsible for, or contribute to, such protective reflexes as cough, sneeze,
      and vomiting, generate the high intra-abdominal pressures necessary for
      defecation and parturition, are active during postural adjustments, and play an
      essential role in vocalization in many species. Despite this widespread
      involvement, however, their control has, with rare exceptions, received little
      attention for two major reasons. First, in most anesthetized or decerebrate
      preparations, they are relatively inactive at rest, in part because the position
      of the preparation (supine or prone with abdomen supported), reduces lung volume
      and, therefore, their activity. Second, unlike phrenic motoneurons innervating
      the diaphragm, identification of motoneurons to a particular abdominal muscle is
      difficult. At the lumbar level, a given motoneuron may innervate any one of the
      four abdominal muscles; at the thoracic level, they are also intermixed with
      those innervating the intercostals. The two internal muscles, the internal
      oblique and the transverse abdominis, respond more to increases in chemical or
      volume-related drive than the two external muscles, the rectus abdominis and
      external oblique; the basis for this differential sensitivity is unknown.
      Segmental reflexes at the thoracic and lumbar levels are sufficient to activate
      abdominal motoneurons in the absence of descending drive but the basis for these
      reflex effects is also unknown. Neuroanatomical experiments demonstrate many more
      inputs to, and outputs from, the nucleus retroambigualis, the brainstem region in
      which the premotor neurons are located, than can be accounted for by their
      respiratory role alone. These other connections likely subserve activities other
      than respiration. Studies of the multifunctional roles of the abdominal muscles,
      on the basis of recent work, hold considerable promise for improving our
      understanding of their control.

PMID- 9775402
TI  - Involvement of basal ganglia transmitter systems in movement initiation.
AB  - The basal ganglia have been implicated in a number of important motor functions,
      in particular in the initiation of motor responses. According to the current
      model of basal ganglia functions, motor initiation is supposed to be associated
      with an inhibition of basal ganglia output structures (substantia nigra pars
      reticulata/entopeduncular nucleus) which, in turn, might be brought about by
      corresponding striatal activity changes conveyed via direct and indirect
      intrinsic pathways to the substantia nigra pars reticulata and the entopeduncular
      nucleus. Rodent studies using neuropharmacological manipulations of basal ganglia
      transmitter systems by neurotoxins or drugs provide converging evidence that
      dopamine within the caudate-putamen, but also within extrastriatal basal ganglia
      nuclei, is involved in motor initiation by modulating the activity of direct and
      indirect intrinsic pathways. However, the striatal segregation of dopamine D1 and
      D2 receptors in control of the direct and indirect projection neurons seems not
      to be maintained throughout the basal ganglia. In dopamine intact animals,
      striatal glutamate plays a major role in response initiation probably through
      actions on striatopallidal neurons involving N-methyl-D-aspartate, but not alpha
      amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors. Striatal
      adenosine might also contribute to movement initiation by acting on adenosine A2A
      receptors located on striatopallidal neurons. Analysis of two integral parts of
      the indirect pathway revealed that inactivation of the subthalamic nucleus was
      found to facilitate response initiation, while inactivation of the globus
      pallidus resulted in facilitation as well as inhibition of response initiation
      indicating a complex contribution of this latter nucleus. Glutamate and gamma
      amino-butyric acid (GABA) controlling the activity of the substantia nigra pars
      reticulata could be involved in control of response initiation in a way predicted
      by the simplified model of basal ganglia functions. In contrast, the role of the
      entopeduncular nucleus in response initiation and its control through GABA and
      glutamate is at variance with this hypothesis, suggesting functional differences
      of the output structures. Taken together, neurochemical systems of the basal
      ganglia significantly contribute to intact response initiation by mechanisms
      which are only partly consistent with predictions of the current functional
      scheme of the basal ganglia. This suggests that a more complex model is required
      to account for these disparate findings.

PMID- 9775403
TI  - The regulation of amyloid precursor protein metabolism by cholinergic mechanisms
      and neurotrophin receptor signaling.
AB  - The increased expression and/or abnormal processing of the amyloid precursor
      protein (APP) is associated with the formation of amyloid plaques and
      cerebrovascular amyloid deposits, which are one of the major morphological
      hallmarks of Alzheimer's disease (AD). Among the processes regulating APP
      metabolism, the proteolytic cleavage of APP into amyloidogenic or
      nonamyloidogenic fragments is of special interest. The cleavage of the APP by the
      alpha-secretase within the beta-amyloid sequence generates nonamyloidogenic C
      terminal APP fragments and soluble APPs alpha, which has neurotrophic and
      neuroprotective activities. Proteolytic processing of APP by beta-secretase, on
      the other hand, exposes the N-terminus of beta-amyloid, which is liberated after
      gamma-secretase cleavage at the variable amyloid C-terminus. The resulting 39-43
      amino acid beta-amyloid may be neurotoxic and disrupt neuronal connectivity after
      its accumulation in senile plaques. In this review, we discuss evidence derived
      from in vitro experiments, suggesting that the stimulation of protein kinase C
      (PKC)-coupled M1/M3 muscarinic acetylcholine receptors increases the
      nonamyloidogenic, secretory pathway of APP processing. It has also been shown in
      animal models that under conditions of reduced M1/M3 muscarinic acetylcholine
      receptor stimulation the secretory pathway of APP processing is inhibited and
      that constitutive upregulation of M1/M3-associated PKC increases APP secretion.
      Thus, the cortical cholinergic hypoactivity characteristic of AD may inhibit the
      nonamyloidogenic APP processing pathway and lead to increased beta-amyloid
      generation. It has been shown in vitro that nerve growth factor (NGF)-associated
      signaling also influences the expression and catabolism of APP. Recent
      experiments with NGF-responsive cells revealed a specific role for the high
      affinity NGF receptor, TrkA, in the increases in secretory APP processing and a
      role for the low-affinity neurotrophin receptor, p75NTR, in the transcriptional
      regulation of APP. Therefore, treatments with NGF could ameliorate cortical
      cholinergic dysfunction in AD. These findings may influence the design of
      therapeutic strategies aimed at stimulating cholinergic function and at
      increasing nonamyloidogenic APP processing without elevating APP expression.

PMID- 9775405
TI  - Squamous cell carcinoma of the esophagus: a review and update.
AB  - Squamous cell carcinoma (SCC) of the esophagus is an often-lethal disease that
      most commonly presents in an advanced stage with dysphagia in elderly patients.
      Known risk factors include alcohol and tobacco abuse, lye stricture, and
      achalasia. Screening protocols for high-risk patients are practiced in Japan but
      not in the United States. The diagnosis usually is made based on the results of
      esophagogastroduodenoscopy and contrast upper gastrointestinal radiographs.
      Staging is determined using computed tomography scanning and esophageal
      ultrasound, the latter rapidly being accepted as a superior method. Treatment is
      based on the stage of disease at presentation. Lesions without metastatic spread
      or mediastinal invasion generally should be treated with esophagectomy. Dysphagia
      associated with advanced lesions is difficult to treat, but may be palliated by
      surgery, radiation therapy, chemotherapy, laser ablation, peroral dilation, or
      esophageal stenting. Despite numerous medical advances, little headway has been
      made in managing and treating SCC, and a multidisciplinary approach is
      recommended.

PMID- 9775404
TI  - Age-related impairment in long-term potentiation in hippocampus: a role for the
      cytokine, interleukin-1 beta?
AB  - Ageing is associated with impairments in a variety of biological functions, one
      of the most striking might be considered to be the impairment in cognitive
      function. This impairment probably relates to the vulnerability of the
      hippocampus to the ageing process, since several cognitive functions rely on the
      integrity of this brain area. Analysis of the mechanisms underlying the effect of
      ageing on hippocampal function has focused to a great extent on analysis of age
      related changes in long-term potentiation (LTP) in hippocampus of experimental
      animals. LTP is a remarkable form of synaptic plasticity which is characterized
      by a persistent increase in synaptic efficacy following tetanic stimulation of an
      afferent pathway to one of the hippocampal subfields. On the basis of its
      properties, LTP has been proposed as a biological substrate for learning and/or
      memory. There is general agreement that aged rats exhibit an impaired ability to
      sustain LTP but there is no agreement on the underlying cause of this deficit. In
      this review, the evidence which suggests that age-related changes in membrane
      composition, triggered by oxidative changes, might significantly contribute to
      the impairment in LTP, is considered. These findings are supported by recent data
      which indicates that dietary supplementation with the antioxidant vitamins, E and
      C, reversed the age-related impairment in LTP, in parallel with reversing the age
      related decrease in alpha-tocopherol concentration and the age-related increase
      in lipid peroxidation. The possibility that the proinflammatory cytokine,
      interleukin-1 beta, triggers several age-related changes in hippocampus is
      considered and, based on the evidence presented, the hypothesis that interleukin
      1 beta plays a significant role in ageing in the hippocampus is proposed.

PMID- 9775406
TI  - The role of radiotherapy in the surgical management of gastrointestinal cancer.
AB  - Surgery is the main mode of treatment in most gastrointestinal malignancies.
      Radiotherapy with or without chemotherapy is playing an increasing role as an
      adjunct to improve local control, survival and palliation. The principles of
      radiotherapy and the rationale for combination therapy are presented. The current
      role of radiation therapy in the GI tract is discussed by various sites. New and
      investigational radiotherapy techniques are outlined.

PMID- 9775407
TI  - Parotid cancer.
AB  - Parotid cancers are relatively rare but will be encountered in any head and neck
      oncology practice. Their histopathological diversity merits a specific
      classification, particularly as prognosis is often closely associated with
      histological type. Tumour stage is also of prognostic significance. Diagnostic
      value of aspiration cytology and frozen section analysis remains unresolved for
      this group of tumours. Surgery remains the mainstay of treatment with primary
      rather than delayed reconstruction of the facial nerve should this be required.

PMID- 9775408
TI  - D2 dissection for gastric cancer.
AB  - Theodore Billroth successfully performed the first gastrectomy for cancer in
      Vienna in 1881. This was the beginning of modern gastric cancer surgery and
      provided the first real hope for cure from this form of cancer. Gastric cancer is
      a leading cause of cancer related mortality world wide, particularly in Central
      and South America, Japan and Korea, and in the Baltic Sea countries. In the
      United States, the incidence of gastric cancer has been on the decline since the
      1930s. In 1996, it was estimated that there were 24,000 new cases of gastric
      cancer with 80-90% expected to die of their disease. The Japanese Research
      Society for Gastric Cancer has classified the draining lymph nodes of the stomach
      and assigned 16 different lymphatic stations. The nodes were then assigned to one
      of four echelons (N1-N4). Different locations of the cancer within the stomach
      require different forms of gastric resections. The Japanese have defined four
      levels of lymph node dissections (D1-D4), where specified lymph nodes from
      assigned lymphatic stations are dissected for a given type of resection. This was
      defined by the General Rules for the Gastric Cancer Study in Surgery and
      Pathology by the Japanese Research Society for Gastric Cancer in 1962 and revised
      in 1994. When a tumor has progressed to the muscularis propria or subserosa (T2),
      8-31% of the second echelon lymph nodes (N2) will contain metastases. When a
      tumor has penetrated the serosa (T3), more than 40% of the second echelon lymph
      nodes will have metastases. Therefore, less than a D2 dissection will
      inadequately stage a significant population of patients. When retrospective
      series are reviewed at institutions committed to performing D2 dissections, the
      overall survival repeatedly shows improved results for patients undergoing D2
      dissections when compared to D1 dissections. Moreover, there have been several
      large trials from all areas of the world which have shown similar morbidity and
      mortality results when D1 and D2 dissections have been compared. To date, there
      have been no trials which have been reproducible that have shown an improved
      survival in patients receiving adjuvant chemotherapy. Intergroup 0116 is
      currently studying the use of adjuvant radiation therapy in gastric cancer. We
      have not come far from the days of Theodore Billroth in the treatment modalities
      for gastric cancer. As surgical expertise and technology have improved, and the
      field of anesthesia has developed, survival of patients has improved. Only the
      extent of lymphatic dissection (D2 dissection) has proven beneficial to the
      outcomes of patients with this disease.

PMID- 9775409
TI  - The evaluation of palpable breast masses: common pitfalls and management
      guidelines.
AB  - The management of a palpable breast mass starts with identification of the lesion
      and a suspicion of malignancy. While seemingly simple, the initial evaluation can
      significantly impact upon treatment options and outcomes. The management of two
      patients recently referred to this Institution highlights common pitfalls and
      technical considerations in the diagnosis and treatment of palpable breast
      masses. The case histories of two patients referred after open breast biopsy were
      examined. The English language medical literature was searched manually and by
      Medline for publications related to the evaluation of palpable breast masses.
      Imaging, diagnostic techniques and technical considerations in the management of
      palpable lesions were reviewed. The initial use of carefully selected diagnostic
      and therapeutic measures is critical in optimizing outcomes measured in improved
      quality of life and survival. Inappropriate choices at this first stage can have
      extremely negative consequences. The early evaluation of two patients highlighted
      these considerations. Management pitfalls included serial examination of a
      suspicious lesion, failure to obtain a mammogram prior to excisional biopsy and
      unnecessary testing. Technical problems included piecemeal excision of the tumor
      with positive margins, use of a drain, closure of deep tissues with dimpling of
      the breast, and incision placement in a location that subsequently necessitated
      mastectomy. Careful adherence to the clinical and operative principles of breast
      cancer management optimizes outcomes in the evaluation of palpable breast masses.

PMID- 9775410
TI  - Statements of the committees of the WHO consensus conference, 20 August 1997. 1st
      International Conference on Urinary Incontinence in the Elderly. Bonn, Germany,
      20-21 August 1997.

PMID- 9775412
TI  - Epidemiology and etiology of urinary incontinence in the elderly.

PMID- 9775413
TI  - The aging bladder: morphology and urodynamics.

PMID- 9775414
TI  - Urge incontinence in the elderly--supraspinal reflex incontinence.

PMID- 9775415
TI  - Consensus report on pelvic floor weakness of the elderly female.

PMID- 9775416
TI  - Medical treatment and medical side effects in urinary incontinence in the
      elderly.

PMID- 9775417
TI  - Interdisciplinary care of urinary incontinence in the elderly.

PMID- 9775418
TI  - National public health policies for prevention and care in urinary incontinence
      in the elderly.

PMID- 9775419
TI  - Genitourinary reconstruction. Part II.

PMID- 9775420
TI  - The transverse ileal tube as second-line modification of the Mitrofanoff
      principle.
AB  - With the advantages of constant availability, minimal loss of bowel, relative
      simplicity (no mesentery interfering with implantation, high mobility of the
      tube), minimized risk of stone formation (no use of staples), reliable continence
      (no leak point) and easy catheterization (longitudinal folds), this
      straightforward technique is an excellent second choice for the Mitrofanoff
      conduit. A longer period of follow-up is needed to determine whether it deserves
      a permanent place in the reconstructive surgeons' repertoire.

PMID- 9775421
TI  - Bowel-flap tubes for continent cutaneous urinary diversion.
AB  - The appendix stoma for Mainz-pouch continent cutaneous urinary diversion is
      reliable and easy to perform. Two new continence mechanisms were developed for
      patients in whom the appendix is not available or usable. A seromuscular tube was
      used in 27 patients (12 women, 15 men, mean age 63 years) and a bowel-wall tube
      was used in 24 patients (13 women, 11 men, mean age 57 years) as the continence
      mechanism for continent cutaneous urinary diversion. At a mean follow-up of 32
      months (range 2-68 months), 93% of patients with a seromuscular tube and 92% of
      those with a bowel-wall tube are continent day and night. Four early and nine
      late stoma-specific complications have occurred, requiring seven open surgical
      revisions. Thus far, both techniques have fulfilled all requirements as
      continence mechanisms for continent cutaneous urinary diversion. However, the
      reliability, advantages, and disadvantages of these techniques have to be
      confirmed in further long-term studies.

PMID- 9775422
TI  - Gastrocystoplasty: is there a consensus?
AB  - The problems encountered with ileal and colocystoplasty have led to the use of
      the stomach for bladder augmentation, termed gastrocystoplasty. The advantages of
      gastrocystoplasty over intestinal segment augmentation include reduced chloride
      reabsorption, decreased mucus production, decreased urinary infection in the
      presence of acid urine, extremely low incidence of stones, and avoidance of
      complications from short bowel syndrome. The gastric patch provides comparable
      improvements in bladder volume, pressure, and continence. The thick muscular wall
      of the stomach facilitates ureteric reimplantation as compared with the small
      intestine, but the rate of stenosis and reflux may not be superior. The
      disadvantages of the gastric patch include complications of severe systemic
      alkalosis, which is usually manifest in dehydrated, renal compromised patients,
      and the hematuria-dysuria syndrome (HDS), which is more prevalent in patients
      with renal insufficiency, normal pelvic sensation, and urinary incontinence. The
      postoperative complication rate of gastrocystoplasty is comparable with that of
      other augmentation procedures and similarly warrants proper selection and close
      follow-up of patients. In this report we review the literature and present the
      results, including a discussion of the technique and the pathophysiology of its
      complications.

PMID- 9775423
TI  - Ureterocystoplasty update.
AB  - Ureterocystoplasty is a unique method for bladder augmentation that lines the
      bladder with transitional epithelium and avoids the potential complications
      associated with enterocystoplasty. Seven patients have undergone
      ureterocystoplasty with excellent long-term results. All have maintained good
      bladder compliance and the contralateral kidney has been protected in all cases.

PMID- 9775424
TI  - Autoaugmentation demucosalized enterocystoplasty.
AB  - Autoaugmentation demucosalized enterocystoplasty has been developed from the
      combination of the autoaugmentation technique, the use of the stomach and colon
      for bladder augmentation and the ability of the bowel and stomach to survive the
      removal of their epithelial lining. The initial combined approach used the
      stomach as the source of muscle, with the colon subsequently being used as an
      alternative. The operations have been applied in the laboratory and clinically,
      giving good results for bladder augmentation with both sources of enteric muscle,
      more reliably so and with a greater ease of separation of the mucosa when stomach
      muscle is used. There is hope that further research will improve the outcome of
      what is a technically challenging procedure.

PMID- 9775425
TI  - Small-intestinal submucosa for bladder augmentation: a review of preclinical
      studies.
AB  - The need to find an alternative to the use of bowel for urinary reconstruction
      has renewed research interests involving bladder regeneration. Historically,
      alloplastic and biodegradable materials have demonstrated bladder regeneration;
      however, high complication rates and unreliable regenerative results have
      prevented any of these materials from being used clinically. Small-intestinal
      submucosa (SIS) is an acellular, nonimmunogenic, biodegradable, xenogeneic,
      collagen-based material that is derived from the submucosa layer of porcine small
      intestine. SIS has demonstrated regenerative capacities in multiple organ
      systems, including the aorta, vena cava, ligaments, tendons, abdominal wall, and
      skin. SIS has also demonstrated long-term reliable regenerative results in the
      rat and canine bladder-augmentation models. This article reviews the preclinical
      studies involving the use of SIS for bladder augmentation.

PMID- 9775426
TI  - Surgery for detrusor overactivity.
AB  - Intractable detrusor overactivity can result in considerable morbidity and, in
      the case of neurogenic bladder dysfunction, can put the upper tracts at risk.
      Once conservative treatments have been exhausted the aim of surgery is to
      increase functional bladder capacity and decrease the maximal detrusor pressure
      at this capacity. The mainstay of contemporary therapy has been augmentation
      cystoplasty; the different techniques and recent literature are reviewed herein.
      Bladder autoaugmentation is compared and contrasted with augmentation cystoplasty
      and its role is discussed, as is the less invasive technique of sacral
      neuromodulation with reference to their role within the range of surgical
      treatments for detrusor activity.

PMID- 9775427
TI  - The antegrade continence enema procedure why, when and how?
AB  - Following the description of the antegrade continence enema (ACE) 7 years ago, it
      has become widely performed and accepted as the most successful treatment for
      intractable faecal incontinence. Modifications of the operative technique and
      enema regimen have been described, but the basic principle remains. This paper
      traces the evolution of the ACE and describes criteria for patient selection,
      operative technique and enema regimens.

PMID- 9775428
TI  - Modifications of and extended indications for the Pippi Salle procedure.
AB  - Total urinary incontinence is a difficult problem faced by the urologist. Several
      techniques to increase ureteral resistance have been described. The majority of
      them rely on intermittent catheterization for bladder emptying, especially in
      neurogenic incontinence. We have developed a new procedure in which a bladder
      flap is used to create a neourethra. This urethral extension acts as a flap valve
      to provide continence. Bladder emptying is accomplished by clean intermittent
      catheterization. Urethral lengthening with an anterior bladder-wall flap was
      performed in 18 patients aged a mean of 8.9 years who had neurogenic incontinence
      (14) or exstrophy (4). Patients with previous bladder interventions received a
      lateralized anterior flap. Bladder augmentation was performed in 14 of the 18
      patients [detubularized ileum (11), detubularized colon (3)]. The average follow
      up period is currently 29.3 months. Continence was achieved in 13 of the 18
      patients (72%). Complications included urethrovesical fistulae, which developed
      in two patients. Two patients could not perform catheterization due to pain but
      had no obstruction to passage of catheter (exstrophy). Ureteral lengthening with
      an anterior bladder-wall flap is a useful alternative for the surgical treatment
      of urinary incontinence. This technique achieves a good continence rate and
      presents few problems with catheterization.

PMID- 9775429
TI  - Defining the role of the bladder-neck sling in the surgical treatment of urinary
      incontinence in children with neurogenic incontinence.
AB  - Patient selection for the creation of a fascial sling procedure to increase
      outlet resistance has been somewhat controversial. We review our experience with
      the fascial sling technique and report our patient selection process. Since 1991,
      30 patients, including 6 males and 24 females aged 4-20 years (mean 10 years),
      underwent a rectus fascial sling procedure as part of their reconstructive
      efforts for continence. The underlying cause of incontinence was neurogenic in 28
      patients. All males were prepubertal. Videourodynamics were performed in all
      patients preoperatively. Criteria for enhancement of bladder-outlet resistance
      included a detrusor leak-point pressure (LPPd) of < 50 cmH2O; a stress leak-point
      pressure (LPPs) of < 100 cmH2O; an open bladder neck, irrespective of LPP, and
      clinical evidence of stress incontinence, irrespective of videourodynamic
      parameters. Technical aspects of the procedure are discussed. Augmentation
      cystoplasty was performed in 29 patients with poor bladder compliance. In 18
      patients a catheterizable stoma was also created. The period of follow-up
      currently ranges from 2 to 70 (mean 37) months. In all, 28 patients (93%) became
      continent and 2 female patients remain incontinent with a low LPP. All patients
      are on clean intermittent catheterization (CIC); 12 patients (40%) are
      catheterizing per urethra without difficulty. All prepubertal males are
      completely dry. The fascial sling repair has many advantages over other methods
      for increasing outlet resistance, including simplicity of technique,
      effectiveness, minimal likelihood of erosion, and low cost.

PMID- 9775430
TI  - Long-term metabolic effects in patients with urinary diversion.
AB  - The use of intestinal segments in genitourinary reconstruction could influence
      vitamin metabolism and affect the skeletal bone and its mineral content in the
      long term. In 137 patients, serum levels of the vitamins A, B1, B2, B6, B12, D,
      and E and of folic acid, bile acid, and ammonia as well as levels of
      intracorpuscular vitamin B12 and folic acid were examined and a red blood cell
      count was performed. The patients were divided into three groups (< or = 2 years,
      > 2 to < or = 4 years, and > 4 years after surgery) as well as into children and
      adults. In addition, bone mineral density (dual-photon absorptiometry) was
      measured in 25 patients. Of these, 16 patients were approximately 16.8 years s/p
      rectal reservoir, 6 were approximately 20.5 years s/p colonic conduit, two were 6
      and 8 years s/p ileocecal pouch, and one adolescent was 5 years s/p ileal bladder
      augmentation. In all patients the levels of vitamins A, B1, B2, B6, D, and E and
      of folic acid, bile acid, and ammonia as well as the red blood cell count were
      within normal ranges. In children (n = 51) there was no significant drop in
      vitamin B12 levels after the operation. In adults (n = 86), serum vitamin B12
      levels dropped significantly from 402 +/- 182 ng/l during the first 2 years after
      the operation to 292 +/- 204 ng/l after the 4th year (normal range 240-1,100
      ng/l). No significant increase in the intracorpuscular vitamin B12 level was
      observed during the same period. The bone mineral density was normal in all 25
      patients with different types of urinary diversion. In addition to regular
      examination (sonography, creatinine levels, and base excess), vitamin B12 levels
      should be determined at 4 years after urinary diversion. It remains unclear
      whether substitution is necessary. However, substitution is easy to achieve and
      cheaper than the regular determination of vitamin B12. No decrease in bone
      mineral content was seen in the long-term follow-up with early correction of the
      base excess (below -2.5).

PMID- 9775431
TI  - Effect of exceptional valine replacement for highly conserved alanine-55 on the
      catalytic site structure of chymotrypsin-like serine protease.
AB  - The catalytic triad consisting of His57, Asp102 and Ser195, which is completely
      conserved within the chymotrypsin-like serine protease family, plays a central
      role in catalysis. Highly conserved Ala55 also likely plays an important role in
      catalysis due to its location just behind the catalytic triad. The only exception
      to the conserved Ala55 in mammalian serine proteases is Val55 in bovine protein
      C. Interestingly, it has been demonstrated that the replacement of Ala55 with Thr
      results in the reduced activity of plasmin in patients with venous thrombosis and
      with retinochoroidal vascular disorders, which indicates the importance of Ala55
      in catalysis. In the present study, we constructed a bovine protein C model which
      shows that Val55 causes no serious rearrangement of the catalytic site structure.
      We also constructed an A55T variant model of trypsin for comparison. The A55T
      substitution alters His57 into an inactive conformation, forming an unusual
      hydrogen bond between Thr55 O gamma 1 and His57 N epsilon 2. The present study
      shows that the Ala/Val55 residue contributes heavily to the active conformation
      of His57 and enables His57 to accept a proton from Ser195 O gamma effectively.

PMID- 9775432
TI  - Synthesis and sedative-hypnotic effects of N3-allyl- and N1-allyl-5,6-substituted
      2-thiouracil derivatives in mice.
AB  - Twenty four thiouracil derivatives, including N3-allyl- (19) and N1-allyl-2
      thiouracil (20) were synthesized and their pharmacological effects [sedative
      hypnotic activity (loss of righting reflex and spontaneous activity), convulsant
      activity, effect on pentobarbital (PB)-induced sleep and mortality] were
      evaluated in mice at doses of 320 mg/kg, i.p. and 2 mumol/mouse by
      intracerebroventricular (i.c.v.) injections, respectively. N3-Allyl-6-propyl-2
      thiouracil (3), N3-allyl-5,6-dimethyl-2-thiouracil (10), N3-allyl
      1,2,3,4,5,6,7,8,9-nonahydro-4-oxo-2-thiocyclohepta [d]pyrimidine (16) and N3
      allyl-5-methyl-2-thiouracil (18) exhibited sedative-hypnotic activity, whereas N3
      allyl-6-ethyl-5-methyl-2-thiouracil (11), N1-allyl-5-methyl-2-thiouracil (21), N1
      allyl-1,2,3,4,5,6,7,8,9-nonahydro-4-oxo-2-thiocyclohepta[ d]pyrimidine (23) and
      N1-allyl-5,6-dimethyl-2-thiouracil (24) conversely displayed clonic- and/or tonic
      convulsant seizures. N3-Allyl-6-propyl-2-thiouracil (3) and N3-allyl-5-methyl-2
      thiouracil (18) decreased spontaneous activity. Other compounds examined were
      inactive, or only slightly active in the sedative-hypnotic assay even at high
      doses. Fifteen compounds (1-4, 7, 10, 11, 14-16, 18-21, and 23) significantly
      prolonged the PB-induced sleeping time. Interestingly, only N1-allyl-5,6-dimethyl
      2-thiouracil (24) shortened the PB-induced sleeping time. These results showed
      that these thiouracils possessed many different effects such as sedative
      hypnotic, anticonvulsant and/or convulsant, and that N3-allyl-5-methyl-2
      thiouracil (18) and N1-allyl-5,6-dimethyl-2-thiouracil (24) had the most potent
      hypnotic activity and antagonistic effect against PB, respectively.

PMID- 9775433
TI  - Amino acids and peptides. LII. Design and synthesis of opioid mimetics containing
      a pyrazinone ring and examination of their opioid receptor binding activity.
AB  - An amino group was introduced to the 3 or 6 position of a pyrazinone ring by
      cyclization of dipeptidyl chloromethyl ketones. Boc-Tyr-OH was coupled with the
      amino function, followed by removal of the Boc group to give pyrazinone ring
      containing tyrosine derivatives. Of the various tyrosine derivatives prepared, 5
      methyl-6-beta-phenethyl-3-tyrosylaminobutyl-2(1H)-pyrazinone exhibited strong
      binding to the mu-opioid receptor with a Ki value of 55.8 nM and to the delta
      opioid receptor with a Ki value of 2165 nM and with a Ki mu/Ki delta value of
      0.026.

PMID- 9775434
TI  - Protective effects of baicalein against cell damage by reactive oxygen species.
AB  - Baicalein (5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one), a naturally
      occurring flavonoid, was found to prevent human dermal fibroblast cell damage
      induced by reactive oxygen species such as hydrogen peroxide (H2O2), tert-butyl
      hydroperoxide (BuOOH) and superoxide anions (.O2-) in a concentration-dependent
      manner, and was more effective than the iron chelator, deferoxamine, hydroxyl
      radical (.OH) scavengers such as dimethyl sulfoxide (DMSO) and ethanol (EtOH),
      the lipid peroxidation chain blocker, alpha-tocopherol (Vit. E) and the xanthine
      oxidase inhibitor, allopurinol. To probe the mechanism of cell defense, the
      reaction of baicalein with oxygen free radicals was investigated using electron
      spin resonance (ESR) spectrometry. Baicalein decreased the signal intensities due
      to the 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) spin adducts of .OH, .O2- and tert
      butyl peroxyl (BuOO.) radicals in a concentration-dependent manner. The IC50
      values, which are the 50% inhibition concentrations of baicalein for the free
      radicals, were 10, 45 and 310 microM, respectively. These results suggested that
      baicalein possesses free radical scavenging ability which prevents the fibroblast
      damage induced by these free radical species.

PMID- 9775435
TI  - Antidiabetic principles of natural medicines. III. Structure-related inhibitory
      activity and action mode of oleanolic acid glycosides on hypoglycemic activity.
AB  - We examined the structure-related activity of oleanolic acid glycosides with
      respect to their inhibitory effect on the increase in serum glucose in oral
      glucose-loaded rats and their mechanism of action using oleanolic acid 3-O
      glucuronide and momordin Ic. Both the 3-O-monodesmoside structure and 28-carboxyl
      group were confirmed to be essential for such activity, and the 3-O-glucuronide
      was more potent than 3-O-glucoside. On the other hand, the 28-ester glucoside
      moiety and 6'-methyl ester of the glucuronide moiety reduced such activity.
      Oleanolic acid 3-O-glucuronide and momordin Ic, both of which inhibited the
      increase in serum glucose in oral glucose-loaded rats, did not lower serum
      glucose in normal or intraperitoneal glucose-loaded rats, or alloxan-induced
      diabetic mice. These glycosides were found to suppress gastric emptying in rats,
      and also inhibit glucose uptake in the rat small intestine in vitro. These
      results indicate that oleanolic acid 3-O-glucuronide and momordin Ic, given
      orally, have neither insulin-like activity nor insulin releasing-activity. They
      exhibit their hypoglycemic activity by suppressing the transfer of glucose from
      the stomach to the small intestine and by inhibiting glucose transport at the
      brush border of the small intestine.

PMID- 9775436
TI  - Structures of three new oleanene glucuronides isolated from Lathyrus palustris
      var. pilosus and hepatoprotective activity.
AB  - Three new saponins, named palustrosides I, II and III, together with
      azukisaponins II, V and soyasapogenol B monoglucuronide, were isolated from the
      aerial parts of Lathylus palustris L. var. pilosus Ledeb. The structures of
      palustrosides I, II and III were identified as 3-O-beta-D-glucopyranosyl-(1-->2)
      beta-D-glucuronopyranosides of soyasapogenol E, abrisapogenol E, and bredemolic
      acid 28-O-beta-D-glucopyranoside, respectively, by spectroscopic and chemical
      methods. As part of our studies on hepatoprotective drugs, we also examined the
      hepatoprotective effects of these saponins towards immunologically induced liver
      injury in primary cultured rat hepatocytes. The activity of the disaccharide
      group was greater than that of the trisaccharide group. This information
      regarding the structure-activity relationships substantiated previously obtained
      data. Structure-hepatoprotective relationships for the sapogenol moiety suggested
      that the hydroxyl group at C-30 reduces the hepatoprotective effect. On the other
      hand, the carbonyl group at C-22 may be equivalent to a hydroxyl group at C-22 in
      terms of hepatoprotective action. Oleanolic acid-type saponins also exhibited
      hepatoprotective action.

PMID- 9775438
TI  - Optimization of the granulation process for designing tablets.
AB  - A computer optimization technique based on surface response methodology was
      applied to optimize the wet granulation process for designing tablets. Physical
      properties (mean granule size, granule size distribution, compressibility,
      granule strength) of a model granule formulation containing ethenzamide were
      accurately described by a second polynomial equation based on two independent
      variables (amounts of binder and binder solution). This regression equation also
      gave a good correlation for three physical properties of tablets (distintegration
      time, compactibility, compression force variance), but the correlation for tablet
      hardness and weight variation was poor. These results imply that not only the
      above physical properties of granules but also the rheological behavior and
      porous structure of granules are closely related to tablet properties. Using an
      optimization of five tablet properties using the generalized distance function,
      the predicted values of the physical properties of both granules and tablets
      agreed well with experimental values. This agreement indicates that the computer
      optimization technique is useful for optimizing the granulation process for
      designing tablets.

PMID- 9775437
TI  - Synthesis and effect of two new penetration enhancers on the transdermal delivery
      of 5-fluorouracil through excised rat skin.
AB  - The tetrahydrogeraniol (THG) derivative, ethyl-(3,7-dimethyl octyl thio) acetate
      (EDOTA) was prepared by reacting tetrahydrogeranyl bromide (obtained by reaction
      of 40% hydrobromic acid and concentrated sulfuric acid) with ethyl 2
      mercaptoacetate, while 3,7-dimethyl octyl propionate (DOP) was synthesized by a
      common esterification reaction by reacting THG with propionic acid in the
      presence of cyclohexane and concentrated sulfuric acid. The penetration-enhancing
      effect of the new enhancers were compared with THG and Azone in vitro using
      excised rat skin in modified Franz-type diffusion cells. 5-Fluorouracil (5-FU), a
      hydrophilic drug with poor skin permeability was used as a model permeant. Skin
      samples were pretreated with pure liquid enhancers for 12 h. 5-FU flux through
      the control and enhancer-treated skin increased linearly with its concentration
      in the receptor compartment. EDOTA and DOP interacted with the skin rapidly (<
      2h), and the duration of action is at least 24 h. Significant differences were
      found in the flux values of 5-FU; EDOTA and DOP enhanced the permeability of the
      drug about 6-fold and 11-fold respectively. Increased partition coefficient and
      diffusion coefficient values were obtained by these enhancers. The results
      suggested that the amount of EDOTA and DOP in the skin, especially in the stratum
      corneum, may be related to their penetration-enhancing effect.

PMID- 9775439
TI  - Antipyretic activity of gingyo-san, a traditional medicine, in influenza virus
      infected mice.
AB  - Gingyo-san is composed of 10 crude drugs and used as a traditional antipyretic
      medicine for the treatment of the common cold and influenza virus infection. In a
      murine intranasal influenza infection model, fever produced by the infection has
      been demonstrated to be reduced by suppressing interferon-induced interleukin
      (IL)-1 alpha production. Thus, we focused on the serum level of IL-1 alpha which
      produces such novel antipyretic activity, and evaluated the relationship between
      defervescence and the suppression of IL-1 alpha production by Gingyo-san in
      influenza virus-infected mice. Fever was produced in the infected mice 33-44 h
      after infection. Oral administration of a hot water-extract of Gingyo-san (8.9
      12.5 mg/0.25 ml/mouse x 3 per day) significantly reduced fever production and
      suppressed the rise in IL-1 alpha production to the level in uninfected mice. No
      apparent toxicity by Gingyo-san was observed in infected mice. When the hot water
      extract of each 10 of the crude components of Gingyo-san (an unknown amount
      extracted from 6.25 mg/0.25 ml/mouse x 3 per day for Saigae Tataricae Cornu and
      3.5 mg/0.25 ml/mouse x 3 per day for the other 9) was orally administered to
      infected mice, 6 showed significant antipyretic activity. Of these 6, Saigae
      Tatricae Cornu significantly suppressed the rise in IL-1 alpha production to the
      basal level while the other 5 did not affect serum IL-1 alpha. Thus, of the 10
      crude components of Gingyo-san, Saigae Tataricae Cornu simultaneously exhibited
      antipyretic and IL-1 alpha-regulatory activities. The novel antipyretic action of
      Gingyo-san may be mainly mediated by Saigae Tataricae Cornu which regulates the
      elevated serum IL-1 alpha level produced by influenza infection.

PMID- 9775440
TI  - Synthesis and pharmacological activities in mice of halogenated delta 9
      tetrahydrocannabinol derivatives.
AB  - Seven halogenated derivatives of delta 9-tetrahydrocannabinol (delta 9-THC, 1)
      substituted on the aromatic ring at the 2 and/or 4 position, 2 (4)-fluoro- (2),
      2,4-difluoro- (3), 2-chloro- (4), 2-bromo- (5), 2,4-dibromo- (6), 2-iodo- (7) and
      2,4-diiodo-delta 9-THC (8) were synthesized and pharmacological effects such as
      catalepsy, anticonvulsant effects, hypothermia, pentobarbital-induced sleep
      prolongation and locomotor activity evaluated by intracerebroventricular (i.c.v.,
      25 micrograms/head) and intravenous (i.v., 5 or 10 mg/kg) injections in mice. The
      cataleptogenic effects of 2 and 5 were about three-quarters and two-thirds,
      respectively, compared to those of 1 (i.v.), though other derivatives were much
      less active (i.c.v. and i.v.). 2 (for clonic seizures) exhibited a significant
      prolongation of seizure latency induced by pentylenetetrazol (i.v.). Hypothermic
      effects of monohalogenated derivatives were comparable to 1 when administered by
      i.v. injection, whereas the effects of dihalogenated derivatives of 1 were
      attenuated. In contrast, 3 and 8 exhibited a significant hyperthermic effect in
      mice. In synergy with pentobarbital, 4 and 5 exhibited a significant prolongation
      of sleeping time by 1.6- and 1.8-fold, respectively, compared with control (32.4
      +/- 2.5 min), although other derivatives did not affect significantly the
      sleeping time (i.c.v.). However, by i.v. injection, 2, 4, 5 and 7 significantly
      prolonged pentobarbital-induced sleeping time and reduced locomotor activity. The
      sleep prolonging effects of 2, 4 and 7 (10 mg/kg, i.v.) were as potent as that of
      1 (5 mg/kg, i.v.). 5 and 7 were the most potent derivatives among the synthetic
      cannabinoids examined in the present study. These results indicate that
      halogenation of 1 leads to modification of the pharmacological profile of THC.

PMID- 9775441
TI  - 2-(3-Pyridyl)thiazolidine-4-carboxamide derivatives. II. Structure-activity
      relationships and active configuration of 2-(3-pyridyl)thiazolidine-4
      carboxamides as platelet-activating factor receptor antagonists.
AB  - Conversion of the 2-(3-pyridyl)thiazolidine part of 1-(3-phenylpropyl)-4-[2-(3
      pyridyl)thiazolidine-4-carbonyl]piperazine (YM461), which is a potent platelet
      activating factor (PAF) antagonist, to other rings was performed, and PAF
      antagonistic activities evaluated. The 2-(3-pyridyl)thiazolidine skeleton, which
      exists as a mixture of cis and trans diastereomers, played an important role in
      the potency of PAF antagonism. In this study, new effective skeletons were not
      uncovered, however, 2-(4-pyridyl)thiazolidine-4-carboxamides (1n and 1z) showed
      potent PAF antagonistic activities equal to the 3-pyridyl derivatives. From the
      results obtained for 1a, 1a(S), 1g and 1i, a cis-(2R,4R)-2-(3
      pyridyl)thiazolidine-4-carboxamide was assumed to be the active configuration for
      PAF antagonism.

PMID- 9775442
TI  - A simple fluorometric determination of vitamin C.
AB  - A simple and accurate method for determination of vitamin C (ascorbic acid (AsA)
      and dehydroascorbic acid (DHA)) using 4,5-dimethyl-o-phenylenediamine (DMPD) was
      investigated. It was found that DMPD is a useful fluorescent reagent. The
      reaction product of DMPD with DHA showed strong and stable fluorescence (Ex; 360
      nm, Em; 440 nm). Fluorometric derivatives were extracted with isobutanol or n
      butanol. Extraction with isobutanol was superior to that with n-butanol in terms
      of specificity, since fluorometric derivatives of keto acids were extracted with
      n-butanol, together with DHA. The fluorescence intensity of DMPD derivatives was
      absolutely stable in isobutanol for at least 24 h. The sensitivity of
      determination of vitamin C was improved by removing several non-fluorometric
      compounds coexisting in the samples. The derivative derived from AsA was easily
      separated from those of keto acids by an HPLC method. The determination of
      vitamin C in natural products was thus improved by extraction and the HPLC
      method.

PMID- 9775443
TI  - Effects of new triphenylethylene platinum(II) complexes on the interaction with
      phosphatidylcholine liposomes.
AB  - In a previous work we synthesized a class of new antineoplastic drugs by coupling
      a cisplatin derivative to a triphenylethylene moiety similar to the antiestrogen,
      tamoxifen. These drugs differ in the number of hydroxy functions on the
      triphenylethylene rings and in the length of the linking arm. To gain more
      insight into the cellular mechanism by which these new drugs act on cells, we
      studied, using differential scanning calorimetry, the effects of these compounds
      on the phase transition of membrane phospholipid (distearoyl phosphatidyl choline
      (DSPC)), and correlated these effects to drug cytotoxicity. The drugs without
      hydroxy function showed the highest cytotoxicity and induced little change on the
      thermogram of DSPC. Contrarily, the drugs bearing two or three hydroxy groups
      were less toxic, but induced important modifications of the thermogram. We
      suggest that the drugs with no hydroxy group enter the membrane, with the
      triphenylethylene moiety localized deep within the hydrophobic core of the
      bilayer and do not affect the cooperativity region (C2-C8). In contrast, drugs
      which bear hydroxy groups on the triphenylethylene rings system perturb the
      phospholipid molecular arrangement; this may be due either to the additional
      steric hindrance of the hydroxy functions in the core of the bilayer, or to their
      hydrophilic effect on the polar head of the lipid. In vitro, the cytotoxic effect
      of these drugs seems not to be related to their affinity for the estrogen
      receptor. We suggest that the addition of a triphenylethylene moiety to the
      platinum(II) complexes increases the hydrophobicity, and consequently the
      resulting drugs become more permeable to the membrane, particularly the non
      hydroxylated triphenylethylene derivatives.

PMID- 9775444
TI  - Potent anticonvulsant paeonimetabolin-I derivatives obtained by incubation of
      paeoniflorin and thiol compounds with Lactobacillus brevis.
AB  - Seventeen thiopaeonimetabolin-I adducts were obtained as mixtures of
      diastereoisomers after incubation of paeoniflorin with Lactobacillus brevis in
      the presence of various thiols. Four compounds, 8-(n-hexylthio)- (8), 8
      cyclopentylthio-, 8-(p-tolyl)thio- and 8-benzoylthio- (18) paeonimetabolins,
      showed 100% protection against pentylenetetrazole-induced convulsions at doses of
      0.125, 0.25, or 0.50 mmol/kg, relative to valproic acid (100% protection at 1.5
      mmol/kg). For 8 and 18, the principle anticonvulsant activity resided in the (7S)
      isomers while (7R)-isomers showed muscle relaxation effects.

PMID- 9775446
TI  - Public reliance on risk communication channels in the wake of a cryptosporidium
      outbreak.
AB  - In the spring of 1993, about 39% of Milwaukee-area residents suffered through a
      nationally publicized illness brought about by cryptosporidium, a parasite that
      had infested the metropolitan drinking water supply. Our study, based on a
      telephone survey of 610 local adult residents, indicates that worry about
      becoming ill in the future with cryptosporidiosis relates more strongly and
      consistently to public reliance on, and use of, media for cryptosporidium
      information than do a range of risk perception and experience variables. We
      propose that more studies should take an audience-centered approach to
      understanding risk communication.

PMID- 9775445
TI  - Synthesis of new peptides with prolactin-releasing activity by a combination of
      recombinant DNA technology and a cysteine-specific cyanylation reaction.
AB  - A newly isolated peptide from bovine hypothalamus with prolactin-releasing
      activity (prolactin-releasing peptide; PrRP) was synthesized by a combination of
      recombinant DNA technology and a cysteine-specific cyanylation reaction, together
      with rat and human homologs. The peptides were expressed in the form of fusion
      proteins with basic fibroblast growth factor mutein, which were purified by
      heparin-affinity chromatography. The fusion proteins were cleaved at the cysteine
      residues of the junction site by cyanylation, followed by treatment with ammonia
      for C-terminal amidation. Purification of the resulting crude peptides was
      performed using chromatography on a gel-filtration column, a cation-exchange
      column, and a reversed-phase column. As an example, about 90 mg of bovine PrRP
      (bPrRP) was obtained from 201 of culture bloth. The purified b PrRP showed full
      biological activities in binding to its receptor expressed on CHO cells and
      releasing arachidonic acid metabolite from the same cells, while the C-terminal
      acid form of bPrRP had little of these activities. These results indicate that
      the C-terminal amide structure is very important for expressing biological
      activity. The peptides obtained here might be very useful for studies on their
      biological significance and roles in vivo.

PMID- 9775448
TI  - A trivariate distribution for the height, weight, and fat of adult men.
AB  - Using exploratory data analysis, probability plots, scatterplots, and computer
      animations to rotate and visualize the data, we fit a trivariate Normal
      distribution to data for the height, the natural logarithm of body weight, and
      the body fat for 646 men between the ages of 50 and 80 years as reported by the
      medical staff of the U.S. Veterans Administration's "Normative Aging Study" in
      Boston, MA. Although these data do not include any children, women, or young men,
      the measurements represent the best data that we could find through a 4-year
      search. We believe that these data are well measured and reliable for men in the
      specified age range and that these data reveal an interesting statistical pattern
      for use in probabilistic PBPK models.

PMID- 9775447
TI  - Health risks of energy systems.
AB  - Health risks from fossil, renewable and nuclear reference energy systems are
      estimated following a detailed impact pathway approach. Using a set of
      appropriate air quality models and exposure-effect functions derived from the
      recent epidemiological literature, a methodological framework for risk assessment
      has been established and consistently applied across the different energy
      systems, including the analysis of consequences from a major nuclear accident. A
      wide range of health impacts resulting from increased air pollution and ionizing
      radiation is quantified, and the transferability of results derived from specific
      power plants to a more general context is discussed.

PMID- 9775449
TI  - Judgments of chemical risks: comparisons among senior managers, toxicologists,
      and the public.
AB  - Nineteen Senior Managers of a major chemical company in the United Kingdom
      participated in a survey to determine their attitudes, beliefs, and perceptions
      regarding risks from chemicals. Similar surveys had previously been conducted
      with toxicologists and members of the general public in the United States and
      Canada. In general, the Senior Managers tended to judge risks to be quite small
      for most chemicals. Moreover, they had lower risk perceptions than did members of
      the British Toxicological Society and even far lower perceptions of risk than a
      comparison group of members of the Canadian public. The managers held views that
      were similar to British toxicologists working in industry and government and
      dissimilar to the views of toxicologists working in academia. The observed
      differences between views of managers, toxicologists, and the public must be
      recognized and understood in order to facilitate communication and constructive
      efforts to manage chemical risks.

PMID- 9775450
TI  - Risk analysis and management of dam safety.

PMID- 9775452
TI  - A probabilistic model for the failure frequency of underground gas pipelines.
AB  - A model is constructed for the failure frequency of underground pipelines per
      kilometer year, as a function of pipe and environmental characteristics. The
      parameters in the model were quantified, with uncertainty, using historical data
      and structured expert judgment. Fifteen experts from institutes in The
      Netherlands, the United Kingdom, Italy, France, Germany, Belgium, Denmark, and
      Canada participated in the study.

PMID- 9775451
TI  - A methodology to select a wire insulation for use in habitable spacecraft.
AB  - This paper investigates electrical overheating events aboard a habitable
      spacecraft. The wire insulation involved in these failures plays a major role in
      the entire event scenario from threat development to detection and damage
      assessment. Ideally, if models of wire overheating events in microgravity
      existed, the various wire insulations under consideration could be quantitatively
      compared. However, these models do not exist. In this paper, a methodology is
      developed that can be used to select a wire insulation that is best suited for
      use in a habitable spacecraft. The results of this study show that, based upon
      the Analytic Hierarchy Process and simplifying assumptions, the criteria
      selected, and data used in the analysis, Tefzel is better than Teflon for use in
      a habitable spacecraft.

PMID- 9775453
TI  - Effect of ethanol ingestion on renal regulation of water and electrolytes.
AB  - Ethanol may alter the homeostasis of water and electrolytes before the occurrence
      of liver damage able to explain these disorders. How the kidney may become
      involved in water diuresis or sodium and potassium retention has not been well
      elucidated. During the last decade, an increasing body of evidence has guided
      interest toward the relevance of the biochemical basis of ethanol-induced injury
      to the kidney. Multiple functional abnormalities of renal tubules may be
      associated with ethanol-induced changes in membrane composition and lipid
      peroxidation of these epithelial cells. Ethanol interferes with the carrier
      function by decreasing (Na+K)-ATPase activity, but this activity is enhanced by
      chronic exposure. Recently, it was reported that ethanol oxidation by the kidney
      is favored in chronic ethanol-treated rats, thereby suggesting a pathogenic role
      for acetaldehyde in the nephrotoxic effect of ethanol ingestion. Also, increased
      reactive oxygen species, partly generated from acetaldehyde oxidation, may
      contribute to the occurrence of oxidative stress. The pathophysiology of renal
      regulation of water and electrolytes of alcoholic disease is analyzed on the
      basis of recent advances in our knowledge concerning the biochemical effects of
      ethanol on the kidney.

PMID- 9775454
TI  - Effect of hypoxia and reoxygenation on metabolic pathways in rat hepatocytes.
AB  - BACKGROUND: The mechanisms whereby rat hepatocytes undergo irreversible injury
      due to a lack of oxygen have not been established. METHODS: Liver cells were used
      for reperfusion injury, and four compartmentalized pathways were evaluated during
      hypoxia (N2/CO2, 19:1) for 30 min followed by oxygen (O2/CO2, 19:1) for 30 min.
      RESULTS: Cell viability decreased during the hypoxic, but not during the
      reoxygenation, phase. Glycogenolysis, as measured by glucose release, was
      significantly increased during hypoxia as compared to controls in oxygen (205 +/-
      15 vs. 155 +/- 10 nmol glucose/mg protein/h, respectively), and did not return to
      normal levels by reoxygenation. Gluconeogenesis was importantly decreased during
      hypoxia (102 +/- 10 vs. 8 +/- 2 nmol glucose/mg protein/h) with partial recovery
      during reoxygenation. Ureagenesis diminished in hypoxia, but recovered during
      reoxygenation. Additionally, 3-hydroxybutyrate formation was augmented by
      hypoxia, with some recovery when oxygen was present. CONCLUSIONS: These results
      suggest that compartmentalized pathways are protected from hypoxic injury in
      isolated hepatocytes, and also suggest it as a model to test the idea that
      enzymes of those pathways are organized into multienzyme complexes in vivo.

PMID- 9775455
TI  - System of 14C-glucose incorporation in axenic cultures of Entamoeba invadens: IP
      1 strain.
AB  - BACKGROUND: It has been described that the walls of the amebic cysts from
      Entamoeba invadens are composed mainly of chitin, a polysaccharide of amino
      sugars. It is also known that the synthesis of this polysaccharide is closely
      related to the degradation of the intracellular glycogen in this organism.
      Nevertheless, it is not known whether the intracellular glycogen is really the
      source of the glucose requirements for the synthesis of the cell wall. METHODS:
      To determine the relationship between the wall cyst synthesis and glycogen
      degradation, it was considered to develop an in vitro culture cell system to
      label this polysaccharide with radioactive glucose. In this study, a system of
      14C-glucose incorporation in axenic cultures of E. invadens was developed. The
      experiments in the study were carried out to recognize if an increase occurred in
      the 14C-glucose incorporation into ameba when the amount of the radioactivity
      used was increased, or whether this incorporation is a dependent metabolic stage.
      RESULTS: The results showed that the amount of glucose incorporation reached
      similar values of 4.5 x 10(-12) mmol per cell in both cases. A different slope in
      the glucose kinetic incorporation between the cultures previously subjected to
      glucose depletion and the standard cultures was observed. CONCLUSIONS: This
      axenic method of radioactive glucose incorporation in Entamoeba invadens could
      facilitate the analysis on a greater scale of the metabolism of this nutrient.

PMID- 9775456
TI  - Intestinal colonization of the infant mouse model by attenuated and virulent
      Vibrio cholerae strains.
AB  - BACKGROUND: Intestinal colonization of humans with virulent Vibrio cholerae
      stimulates substantial, lasting immunity against reinfection. The purpose of this
      study was to evaluate the colonizing capability of various Vibrio cholerae
      strains which are promising candidates to oral vaccine. METHODS: Infant mouse
      model modification was used. In order to standardize the method, several
      parameters were tested, such as culture medium and optimal time of incubation and
      appropriate number of cells to be inoculated. The following were tested: Vibrio
      cholerae strain 81, 413, and 251A, which were obtained at the Molecular Biology
      Department of the National Center for Scientific Research, Havana, Cuba. Their
      virulence cassettes which code for the main virulence factors were deleted.
      RESULTS: Good variance coefficient (VC) was obtained in repeated experiments. The
      colonizing properties of attenuated Vibrio cholerae strains evaluated by this
      method correlated well with those observed for parental strains. CONCLUSIONS:
      Genetically attenuated Vibrio cholera strains have the same intestinal
      colonization level as their parental strains in the infant mouse model; thus,
      genetic manipulation does not affect genes that encode for the synthesis of
      colonization factors.

PMID- 9775457
TI  - Genotoxic evaluation of norfloxacin and pipemidic acid with the Escherichia coli
      Pol A-/Pol A+ and the ames test.
AB  - BACKGROUND: Genotoxicity of antibiotics has not been well evaluated, and there is
      not much information on the genetic risk of quinolone drugs, even though they are
      widely used as alternative choice drugs in urinary infections. METHODS: Pipemidic
      acid and norfloxacin were tested for their capacity to induce point mutations
      using the Ames test and DNA damage on Escherichia coli PolA-/PolA+. RESULTS: At
      non-toxic doses, all of the drugs studied were negative on the E. coli PolA
      /PolA+ test with or without in vitro metabolic activation with induced arochlor
      1254 rat liver (S9). They did not produce frameshift mutations in TA98, or base
      pair substitutions in S. typhimurium hisG46 strains TA100, or UTH8414.
      Norfloxacin and its induced metabolites in vitro with S9 rat liver were mutagenic
      to hisG48 strains TA102 and TA104, both of which detect oxidative chemicals.
      Pipemidic acid induced mutations in S. typhimurium hisG48 strains only when they
      had an efficient DNA excision repair system. CONCLUSIONS: These results suggest
      that the risk of oxygen-free radical generation from quinolones should be
      considered.

PMID- 9775458
TI  - Electrocardiographic alterations in chronically Trypanosoma cruzi-infected
      persons exposed to cardiovascular factors.
AB  - METHODS: We analyzed the potential influence that associated risk factors (ARF),
      such as smoking, alcoholism, overweight, and hypertension, could have on the
      establishment of chronic chagasic cardiomyopathy (CC). The sample was comprised
      of 124 individuals, 69 males and 55 females (mean age +/- SD, 41 +/- 9.5 years),
      who were born in en demic areas of Northern Argentina and migrated further to
      Rosario City, an area where autochthonous cases of Chagas' disease have never
      been registered. Assessments included the following: clinical examination to
      discard previous cardiomyopathies; search for the presence of ARF according to
      standard criteria; specific serology; frontal chest X-ray, and 12-lead resting
      electrocardiogram (ECG). Subjects were classified on the basis of their
      serological status and presence of ARF into four groups: Tc+ARF+ T. cruzi
      infected persons with ARF (n = 41); Tc-ARF+ seronegativity in presence of ARF (n
      = 27); Tc+ARF- individuals showing positive serology that lacked ARF (n = 27),
      and Tc-ARF- seronegative individuals having no ARF (n = 29). RESULTS: Except for
      a higher female/male ratio in groups presenting no ARF (p < 0.02), no statistical
      differences as to age, length of residence in endemicity areas (LR), and ARF
      distribution were recorded among groups. Forty-one persons presented abnormal ECG
      tracings, distributed thus: Tc+ARF+, 18/41; Tc-ARF+, 14/27, Tc+ARF-, 14/27, and
      Tc-ARF, 4/29 (p < 0.01, in relation to the latter group). Subjects from the
      Tc+ARF+, Tc-ARF+, and Tc+ARF- groups had 4.89-, 6.7-, and 6.7-fold increases,
      respectively, if having an abnormal ECG when compared with Tc-ARF- individuals.
      Comparisons on the frequency of abnormal ECG between seropositives carrying ARF
      or not yielded a non-significant odds ratio, be it estimated as crude, or after
      adjusting for sex, age, and LR in multivariate analysis. CONCLUSIONS: Presence of
      ARF was not associated with an increasing risk of cardiac affectation in
      chronically T. cruzi-infected persons, but resulted in chagasic-compatible ECG
      abnormalities in those seronegative individuals.

PMID- 9775459
TI  - Use of prenatal phenobarbital in the prevention of subependymal/intraventricular
      hemorrhage in premature infants.
AB  - BACKGROUND: Subependymal/intraventricular hemorrhage (SE/IVH) is a frequent cause
      of disability and mortality. METHODS: This is a prospective, randomized, double
      blind study which included 100 pregnant Mexican women who need to interrupt their
      pregnancy within 28-32 weeks of gestation. One group was given a single dose of
      intravenous (IV) phenobarbital 10 micrograms/kg (phenobarbital group, n = 50),
      and the other was provided with diluted distilled water (control group).
      Measurements of phenobarbital serum concentrations were taken by both mother and
      newborn, and head sonograms were applied during the first 24 hours, at the 3rd
      and 7th days of life. RESULTS: The sample was made up of 42 newborns in the
      phenobarbital group, and 46 in the control group; the newborns had phenobarbital
      levels of 11.5 5.7 g/microliter at birth, and of 9.5 +/- 5.9 g/microliter 24
      hours later. SE/IVH was found in 12 patients from the phenobarbital group and in
      29 from the control group (p < 0.005), the first group were 11 mild SE/IVH (2
      grade I, and 9 grade II), and 26 in the control group (4 grade I, and 22 grade
      II), p < 0.005. Severe hemorrhages were similar between groups. A larger
      frequency of SE/IVH was found in the newborn group which received mechanical
      ventilation (p = 0.0008). CONCLUSIONS: Prenatal phenobarbital can reduce the
      SE/IVH frequency in premature infants younger than 32 weeks at birth. Its main
      effect could be shown in patients with mechanical ventilation.

PMID- 9775460
TI  - Risk factors for osteoporotic hip fractures in Mexicans.
AB  - BACKGROUND: Osteoporosis (OP) and its fractures are a major problem due to their
      impact in morbidity and mortality in the elderly. Although this entity is well
      studied in other countries, OP and its fractures have not been evaluated
      carefully in our population. The objective was to assess risk factors for
      osteoporotic hip fracture in Mexicans. METHODS: A total of 295 subjects, 152
      cases and 143 controls, were studied. Cases were patients with hip fracture, of
      both sexes and 45 years of age or older. Controls were healthy subjects who were
      in hospital waiting rooms accompanying patients without hip fractures. A
      questionnaire covering known possible risk factors for osteoporotic hip fracture
      was administered by the same evaluator to all subjects. Pelvic roentgenograms,
      anterior-posterior view, were obtained in both cases and controls to perform the
      Singh index and the cortical index of the femur. RESULTS: Fractures were present
      in (72.2%) of women. Weight and any alcohol ingestion were associated with an
      increased risk of hip fracture. The odds ratio (OR) for low weight by the
      Quetelet Index was 4.03 (95% CI 1.93-8.39) p < 0.001. Any alcohol intake was
      associated with an OR of 1.73 (95% CI 1.04-2.90) p < or = 0.03 for the total
      group, and 2.78 (95% CI 1.25-6.14) p < or = 0.003 for women. Controls had a
      significantly higher mean daily calcium intake compared to cases (mean, SD 575.9
      +/- 297.2 vs. 490.4 +/- 245.5, p < or = (0.007). Family history, smoking,
      physical activity, pregnancies, breastfeeding or concomitant diseases were not
      associated with risk of hip fracture. CONCLUSIONS: This study confirmed the risk
      factors for osteoporotic hip fracture in Mexicans, previously shown for other
      ethnic groups. Further research in different factors, such as rate of bone
      turnover, anthropometric dimensions, and genetic studies (osteoporosis gene) are
      needed in order to define the differences among ethnic groups.

PMID- 9775462
TI  - Factors associated with non-use of Pap test. A population survey.
AB  - BACKGROUND: Cervical cancer is the most important cancer in Mexican women. Early
      detection is possible by means of the Papanicolaou (Pap) test; however, the
      coverage in Mexico is low. METHODS: A cross-sectional survey was carried out in a
      representative sample of women from the Tlalpan area of Mexico City. Social,
      reproductive and health care factors associated with the lack of use of the Pap
      test with respect to adequate use and misuse were identified. Both bivariate and
      logistic regression analyses were used for the adjustment of variables. RESULTS:
      Of 1,215 women studied, 22.5% had never had a Pap smear, 42% had misused the test
      (< 90% of triennial performance), and 35.5% had adequately used the test (> or =
      90% of triennial performance). The main factors related to the lack of use were
      the following: not knowing about the Pap test (ORa = 35.16, 95% C.I. = 17.4
      70.9); having fewer than 6 years of education (ORa = 4.5, 95% C.I. = 2.5-8.4);
      women younger than 30 years of age (ORa = 3.4 95% C.I. = 2.3-5.1); use of
      contraceptives (ORa = 0.4, 95% C.I. = 0.2-0.8); history of sexually transmitted
      diseases (ORa = 0.3, 95% C.I. = 0.1-0.8), and the principal informant about the
      Pap test, i.e., the health services personnel (ORa = 0.02, 95% C.I. = 0.0008
      0.05). CONCLUSIONS: The lack of use and the misuse of Pap smears vary importantly
      among the different social and reproductive factors. But the principal reasons
      for lack of use were not knowing about the Pap test and a low educational level.
      We propose a greater diffusion on the benefits of the test in the Mexican
      population, through massive means of communication and health services.

PMID- 9775461
TI  - Risk factors for steroid diabetes in rheumatic patients.
AB  - BACKGROUND: Steroid induced diabetes (SDM) has been known for a long time, but
      its pathophysiological mechanisms as well as its predisposing factors remain
      unknown. METHODS: In order to investigate the different factors related to the
      development of steroid diabetes (SDM) in patients with rheumatic diseases, we
      studied 27 patients with SDM, and 27 age- and sex-matched controls who also
      received therapy with glucocorticoids. In every case, family history of DM, body
      mass index, associated treatment, steroid dose and treatment duration were
      studied; fasting serum insulin, "C" peptide, growth hormone and glucagon levels
      were measured. RESULTS: All of the patients received prednisone. Cumulated
      prednisone dose was the only factor significantly associated with the development
      of SDM. Patients with SDM had a cumulated dose of 26.6 +/- 28 g (M +/- SD), while
      the control group received 11.6 +/- 11 g (p < 0.02) (odds ratio, 6.35). Serum
      insulin levels were not significantly different, but insulin/glucose ratio was
      lower in SDM (0.104 +/- 0.05) than in the control group (0.163 +/- 0.07) (p <
      0.05). CONCLUSIONS: These findings suggest that high cumulated prednisone dose
      may induce DM regardless of another hereditary or personal predisposing factor.

PMID- 9775463
TI  - Odontogenic myxoma: case report with reconstructive considerations.
AB  - Odontogenic myxoma is a benign but locally aggressive neoplasm. The present case
      documents the resective and reconstructive management of a patient with a
      moderately large myxoma of the mandible.

PMID- 9775464
TI  - Fibrin sealant fixation of a skin graft in mandibular vestibuloplasty. Case
      report.
AB  - Fibrin sealant fixation of a skin graft without the use of sutures or a stent in
      mandibular vestibuloplasty is presented in this case report. The advantages of
      the fibrin sealant in preprosthetic surgery are discussed.

PMID- 9775465
TI  - Cracked tooth syndrome--incidence, clinical findings and treatment.
AB  - Cracked tooth syndrome (CTS) is a common occurrence in modern general practice.
      This article reviews the forces placed on the human dentition and the effect
      restorative dentistry has on the strength of tooth structure. The study reports
      on the incidence of CTS in a general practice, finding a far higher incidence in
      teeth which have had the marginal ridge restored than those which have not. The
      various types of treatment modalities advocated and their relative merits are
      discussed.

PMID- 9775466
TI  - The use of titanium mesh sheet in the fronto-zygomatico-orbital region. Case
      reports.
AB  - Six cases reconstructed in the zygomatico-fronto-orbital region with titanium
      mesh are reported and a discussion of the use of this material in oral and
      maxillofacial surgery is presented.

PMID- 9775467
TI  - Cemento-ossifying fibroma with mandibular fracture. Case report in a young
      patient.
AB  - The cemento-ossifying fibroma is classified as an osteogenic neoplasm of the
      jaws. It commonly presents as a progressively growing lesion that can attain an
      enormous size with resultant deformity if left untreated. A case of a large
      cemento-ossifying fibroma involving the left mandible is described in a 15 year
      old male patient. The clinical, radiographic and histological features as well as
      surgical findings are presented. The treatment of choice of this lesion is also
      emphasized. Two years after surgery, there was no evidence of recurrence and the
      transosseous wire used to immobilize the fracture was found to be completely
      buried in the jaw bone.

PMID- 9775468
TI  - Massive residual dental cyst: case report.
AB  - A case report is presented of a massive residual dental cyst that involved over
      half an edentulous mandible. Presentation, diagnosis and management of the
      massive cyst is discussed.

PMID- 9775469
TI  - Langerhans' cell histiocytosis of the jaw bones. Report of 11 cases.
AB  - Eleven cases of Langerhans' cell histiocytosis of the jaw bones are reported. The
      clinical and radiographic features are described, and the role of the dentist in
      the diagnosis and management of this disorder is discussed.

PMID- 9775470
TI  - Post-extraction bleeding--an aid to diagnosis? Case report.
AB  - Haemophilia A, the most common of bleeding disorders is characterized by bruising
      and spontaneous bleeding into the joints but may remain undiagnosed if present in
      the mild form. A case is discussed where episodes of bruising and joint swelling
      as a child were misdiagnosed as rheumatic fever and the bleeding disorder was
      diagnosed following recurrent episodes of bleeding after extraction of an upper
      molar tooth.

PMID- 9775471
TI  - Candida-associated denture stomatitis. Aetiology and management: a review. Part
      3. Treatment of oral candidosis.
AB  - Treatment of oral candidosis with topical antifungal agents such as nystatin and
      amphotericin B is effective initially. However, medication can produce side
      effects in some patients and when therapy is stopped the condition can recur.
      Alternative treatment involving the use of antiseptics and disinfecting agents
      has been shown to play an important role in the control of dental plaque. The use
      of sodium hypochlorite as an overnight denture soak has been shown to eliminate
      denture plaque and recent investigations have demonstrated that microwave
      irradiation of dentures at a specified setting and exposure time is bactericidal
      and candidacidal.

PMID- 9775472
TI  - Sodium hypochlorite and its use as an endodontic irrigant.
AB  - Sodium hypochlorite has been used as an endodontic irrigant for more than 70
      years, and is now one of the most common solutions for this purpose. The chemical
      properties and production of commercial sodium hypochlorite are reviewed.
      Domestic bleaches and an infant sanitizer are compared from the point of view of
      cost and ease of use--Milton being recommended where a 1% solution is required.
      The cost of syringes and needles for endodontic irrigation is many times greater
      than the hypochlorite they contain, and total annual practice costs for
      hypochlorite are low. Brief guidelines for clinical use, storage, handling and
      disposal are included.

PMID- 9775473
TI  - A survey of oral health in a population of adults with developmental
      disabilities: comparison with a national oral health survey of the general
      population.
AB  - During 1991, an oral health assessment of 101 adults with developmental
      disabilities aged from 21 to 53 years was undertaken as part of a broader health
      survey which also included medical, psychological and nutritional assessments.
      The study group consisted of a random sample of adults chosen from the
      developmentally disabled population known to be living in the lower North Shore
      area of Sydney. This paper describes the results of the oral health assessment
      and compares them with an oral health survey of the Australian population done in
      1987/88. Forty-six per cent of the study group were males (mean age 33.5 years)
      and 54 per cent were females (mean age 33.0 years). Compared with similar age
      subgroups in the Australian population, the following factors were more
      frequently reported in the developmentally disabled group: a dental visit in the
      last 12 months (65 per cent vs 50 per cent; Odds Ratio (OR) 1.9:95 per cent
      Confidence Interval (CI): 1.3-2.8); use of public rather than private dental
      services (42 per cent vs 6 per cent; OR 11.3:95% CI 7.5-16.9); oral mucosal
      pathology requiring treatment (15 per cent vs 2 per cent; OR 8.5:95% CI 5.2
      13.8); severe periodontal disease (16 per cent vs 3 per cent; OR 6.9:95% CI 4.2
      11.4); and moderate to severe malocclusion (26 per cent vs 11 per cent; OR
      2.1:95% CI 1.3-3.5). Fifty-eight per cent of subjects felt they needed no dental
      treatment but on examination of the oral mucosa, periodontal tissues and teeth,
      over 90 per cent were found to require some sort of dental treatment.

PMID- 9775474
TI  - An in vitro study of apical and coronal microleakage of laterally condensed gutta
      percha with Ketac-Endo and AH-26.
AB  - The purpose of this in vitro study was to compare both apical and coronal dye
      penetration when Ketac-Endo and AH-26 sealers were used with laterally condensed
      gutta percha. Crowns were removed from 28 teeth and the root canals were
      biomechanically prepared. The teeth were divided into two groups of 12-teeth each
      and a control group of 4 teeth. Root canals in the two experimental groups were
      filled with laterally condensed gutta percha and either Ketac-Endo or AH-26
      sealer. The Ketac-Endo group had the coronal 3 mm of gutta percha and sealer
      removed and the resultant cavity was filled with Ketac-Endo alone. After the
      sealers had set, the root surfaces were coated with nail varnish except at the
      apex and at the coronal end. Positive controls had no root fillings and were
      coated with nail varnish in the same manner while the negative controls were
      sealed apically and coronally with Cavit prior to sealing the entire external
      root surface with nail varnish. Specimens were placed in 2% methylene blue dye in
      a vacuum of 660 mm of mercury for five minutes and then left immersed for a
      further two days. The roots were vertically sectioned to determine the following
      mean levels of dye penetration: Ketac-Endo, 1.08 mm apically and 6.29 mm
      coronally; AH-26, 0.75 mm apically and 6.67 mm coronally. Positive controls had
      total leakage and negative controls had no leakage. This study demonstrated that
      the apical and coronal seals obtained with Ketac-Endo and AH-26 were not
      significantly different although the apical seal obtained with each material was
      significantly better than the corresponding coronal seal.

PMID- 9775475
TI  - Genetic aspects of dental disorders.
AB  - This paper reviews past and present applications of quantitative and molecular
      genetics to dental disorders. Examples are given relating to craniofacial
      development (including malocclusion), oral supporting tissues (including
      periodontal diseases) and dental hard tissues (including defects of enamel and
      dentine as well as dental caries). Future developments and applications to
      clinical dentistry are discussed. Early investigations confirmed genetic bases to
      dental caries, periodontal diseases and malocclusion, but research findings have
      had little impact on clinical practice. The complex multifactorial aetiologies of
      these conditions, together with methodological problems, have limited progress
      until recently. Present studies are clarifying previously unrecognized genetic
      and phenotypic heterogeneities and attempting to unravel the complex interactions
      between genes and environment by applying new statistical modelling approaches to
      twin and family data. Linkage studies using highly polymorphic DNA markers are
      providing a means of locating candidate genes, including quantitative trait loci
      (QTL). In future, as knowledge increases; it should be possible to implement
      preventive strategies for those genetically-predisposed individuals who are
      identified to be at risk.

PMID- 9775476
TI  - Everybody's business or nobody's business.

PMID- 9775477
TI  - Reaction following lignocaine hydrochloride infiltration.

PMID- 9775479
TI  - Vaccine safety resource materials for health-care providers and the public.

PMID- 9775478
TI  - Canadian Consensus Conference on a National Immunization Records System.

PMID- 9775480
TI  - Experiences of mothers in five countries whose child died of cancer.
AB  - Although increasing attention is being focused on the emotional aspects of caring
      for dying children and their families, few research reports concentrate on the
      experiences of mothers, particularly in different countries. This article
      describes the findings of an exploratory, descriptive study that investigated the
      experiences of mothers from five different countries who each had a child die
      from cancer in the past 6 months. Principal investigators, members of the
      International Work Group on Death, Dying, and Bereavement, conducted
      semistructured interviews with 21 mothers in their own countries. No culturally
      related differences were noted among mothers, and the mothers' recall of their
      experiences are more similar than different. All mothers, irrespective of
      country, described similar reactions to the diagnosis, management of the end
      stage illness, and challenge of coping with bereavement. Lessons learned from
      this project provide suggestions for future research across countries.

PMID- 9775481
TI  - Hospice patients' and nurses' perceptions of self-care deficits based on symptom
      experience.
AB  - Although the relief and/or control of physically, emotionally, and spiritually
      distressing symptoms are the hallmarks of hospice care, accurate assessment of
      the individual's unique and often rapidly changing symptom experience is lacking.
      The purpose of this descriptive, correlational study was to assess and quantify
      hospice patients' perceptions of their symptom experiences and those of the
      hospice nurse assessing them. A convenience sample of 53 hospice patients (32
      males, 21 females), with a mean age of 69 years, from a large midwestern home
      based hospice completed the Adapted Symptom Distress Scale Form 2 (ASDS-2) at
      admission, and at 2 and 4 weeks after admission. The Hospice Admission Intake was
      completed at admission. Individual hospice nurses completed the ASDS-2 within 24
      hours of their hands-on assessment, in addition to the demographic
      characteristics profile. Findings indicated an improvement in symptom experience,
      distress, and occurrence scores from admission to week 2, and in the symptom
      experience and distress scores from admission to week 4. Hospice nurses tended to
      give higher symptom experience scores than the patients gave to themselves. These
      findings demonstrate the importance of obtaining information about symptom
      experience from the patient as well as the nurse.

PMID- 9775482
TI  - Measuring impact of nursing intervention on cancer patients' ability to control
      symptoms.
AB  - Cancer patients' ability to control symptoms and to maintain reasonable quality
      of life is limited due to lack of knowledge, guidance, and instructions from
      health care providers, who usually refrain from transferring responsibility for
      the treatment to the patient. The present study describes a measured effect of a
      structured nursing intervention in which nurses were trained to apply the self
      care model to 48 ambulatory cancer patients under chemo- or radiotherapy or both.
      The intervention included 10 structured home visits to each patient during 3
      months, in which the nurse assessed symptoms and advised, guided, supported, and
      educated the patient in the relevant areas. The symptoms were quantitatively
      assessed using the Symptom Control Assessment (SCA) instrument, which was
      developed and validated specifically for this study. The SCA relates to 16 signs,
      symptoms, and complaints that encompass both the universal and the deviation-from
      health needs, in addition to anxiety, body image, and sexuality. The instrument
      allows either the patient or the nurse to rate the severity of the complaint, the
      patient's independence in controlling it, the patient's perception of the
      familial and external help extended to him or her, and the knowledge of the
      symptom and its control possessed by the patient. Also, the SCA allows comparing
      the patient's ratings with the professional view of the visiting nurse. The SCA
      was proven to be a highly reliable and valid instrument. The results indicate
      that the intensity of the complaints decreased in the experimental group during
      the 3-month period while they increased in the matched control group, creating a
      considerable difference between the two groups on multivariate analysis of
      covariance (MANCOVA). On t-tests, significant improvement was found in 15 out of
      the 16 symptoms, including pain. The greatest reduction was found in the
      "psychosocial symptoms," namely anxiety, sociability, body image, and sexuality.
      Similarly, the patients' independence, knowledge, and perception of familial help
      increased in the experimental group and declined in the control group. Perhaps
      the most meaningful change was a significant increase in the ability of the
      experimental patients to assume responsibility for their own treatment as it is
      reflected by the increase of the independence ratings for all 16 symptoms. This
      is in sharp contrast to the decrease in 15 of the 16 symptoms among control
      patients. The results suggest that the self-care approach is effective also in
      improving the quality of life for unstable cancer patients by reduction of
      suffering and increase in controlling capabilities.

PMID- 9775483
TI  - Acculturation and Pap smear screening practices among college-aged Vietnamese
      women in the United States.
AB  - The purposes of this study were both to gather information on the prevalence of
      Pap smear screening among college-aged Vietnamese women and to identify
      predictive factors that influence Vietnamese women to engage in early cervical
      cancer detection behavior. This study also examines the role of acculturation in
      explaining cervical cancer screening behavior. Data were collected through mail
      and telephone surveys. Of those respondents (n = 207), approximately one-third
      (36.8%) reported having had a Pap smear. More than one-third (39.3%) of sexually
      active respondents reported never having had a Pap smear. Acculturated women were
      more likely to be sexually active and to be obtaining regular Pap smears. In the
      logistic regression model, marital status, sexual activity, and a belief that
      only married women should have a Pap smear were important predictors of prior
      reported Pap smear experience. These study findings suggest that less
      acculturated women appear to have the belief that cervical cancer screening is
      more important for married women than for unmarried women, regardless of their
      sexual activity. The existence of such misconceptions underscores the importance
      of offering culturally relevant cancer education that addresses related
      misconceptions.

PMID- 9775484
TI  - Nonadherence to follow-up treatment of an abnormal Pap smear: a case study.
AB  - This article is a case study of a 32-year-old African-American woman diagnosed
      with an abnormal Pap smear, who did not follow through with the recommended
      colposcopy procedure. This case study highlights the role of illness explanatory
      models in nonadherence to follow-up treatment for an abnormal Pap smear. Illness
      explanatory models are an individual's personal interpretation of the illness.
      Research indicates that patients' illness explanatory models may not agree with
      biomedical explanations, but may sometimes have an adverse impact on health and
      illness behavior. This case study draws attention to the impact of illness
      explanatory models of cancer resulting from experience with cancer in the family,
      personal belief systems, and spiritual faith on the patient's decision not to
      follow through with recommended treatment for an abnormal Pap smear. Addressing
      illness explanatory models is of clinical importance in determining methods that
      will motivate women to follow through with treatment protocols when diagnosed
      with an abnormal Pap smear. Further in-depth study of the role these explanatory
      models of cancer play in nonadherence to treatment protocols is needed.

PMID- 9775485
TI  - Perceived benefits: a predictor of participation in prostate cancer screening.
AB  - Prostate cancer is the most frequently diagnosed major cancer and the second
      cause of cancer-related deaths among men. With early detection through screening
      and timely treatment, 9 out of 10 men will survive a minimum of 5 years. However,
      with late diagnoses, only 3 out of 10 men will have a 5-year minimum survival
      rate. Guided by a conceptual map, this correlational research examined perceived
      benefits as a predictor of participation in free prostate cancer screening.
      Perceived benefits are the personal belief and valuing of screening for early
      detection of prostate cancer. All subjects received one of four educational
      interventions: traditional, peer educator, client navigator, or combination.
      Participation in prostate cancer screening was measured by compliance with the
      American Cancer Society's Guidelines, which included a digital rectal exam (DRE)
      and/or a prostate-specific antigen (PSA) blood test. The purposive sample (n =
      1,522) of men, ages 40 to 70 years, was recruited from randomly selected
      churches, barbershops, industries, housing projects, and car dealerships in a
      southeastern state. Seventy-two percent of the sample was African American.
      Predictors of participation in free prostate cancer screening were these:
      perceived benefits, being white, having at least a high school education, being
      married, and receiving the client navigator or combination educational
      intervention. The Benefits Scale was significant (p = 0.013, odds ratio (OR) =
      1.059) as a predictor for participation in screening when all demographic
      variables and educational interventions were controlled. Practice implications
      for nursing are discussed and recommendations for future research are presented.

PMID- 9775486
TI  - Self-transcendence in older men attending a prostate cancer support group.
AB  - Self-transcendence has been shown to be related to well-being in older adults,
      women with breast cancer, women with AIDS, gay men with AIDS, and a healthy
      population. The purpose of this descriptive pilot study was to examine self
      transcendence in another high-priority population: older men with prostate
      cancer. A convenience sample of 23 men, age 60 and older (M = 69), from three
      prostate cancer support groups completed Reed's Self-Transcendence Scale (STS)
      and a demographic data form. The men were predominantly white (82.6%), of the
      Catholic faith (56.5%), married (78.3%), and not working (87.0%). Over half
      (65.2%) had a college degree or higher; most viewed their health as good (69.6%)
      or excellent (21.7%); and the majority (56.5%) viewed their prostate cancer as
      affecting some of their daily activities. These men scored high on the STS (M =
      50.07), which was consistent with previous findings in other populations.
      Findings of this study contribute to Reed's middle-range theory of self
      transcendence. The discovery that self-transcendence is relevant to this group of
      older men with prostate cancer provides a basis for nurses to investigate the
      phenomenon in this population and help their clients explore the benefits of the
      self-transcendence resource.

PMID- 9775487
TI  - Cancer patients' reported experiences of suffering.
AB  - This study describes the nature and content of experiences of suffering by
      patients with incurable cancer. The main body of data was collected in
      interviews. A structured questionnaire was administered for additional
      information. Three different dimensions were identified in patient experiences of
      suffering: physical, psychologic, and social. Suffering has a physical
      foundation, which was divided into two categories: that caused by the illness
      itself and that caused by treatment of the illness. The primary sources of
      physical suffering were fatigue, pain, and the side effects of chemotherapy. The
      causes of psychologic suffering lie in the physiologic changes associated with
      the disease and in the imminence of death. Psychologic suffering was most
      typically manifested in depression, which most of the patients suffered during
      the initial stages of the disease, when the disease metastasized, and when they
      were in a particularly poor condition. General deterioration and fear of
      infections very much restrict the social life of cancer patients, causing them to
      withdraw into their home or the hospital.

PMID- 9775488
TI  - Reliability and validity of the Multidimensional Fatigue Inventory (MFI-20) and
      the Rhoten Fatigue Scale among rural cancer outpatients.
AB  - Cancer patients typically experience fatigue while undergoing treatment for their
      disease. This study was an effort to identify a reliable and economical measure
      of fatigue. In particular, scores on the five subscales of the Multidimensional
      Fatigue Inventory (MFI-20) were analyzed for internal consistency and then
      correlated with scores on the Rhoten Fatigue Inventory to establish a measure of
      validity. Moderate-to-high Cronbach alphas coefficients were established for the
      General Fatigue subscale of the MFI-20 using a sample of 97 rural oncology
      outpatients (1). Partial associations with the Rhoten Fatigue Scale lend evidence
      to the validity of the MFI-20 measures.

PMID- 9775489
TI  - Recommendations for management of severe enterovirus infection in Taiwan.

PMID- 9775490
TI  - Assessing the value of pediatrics journals.
AB  - The pediatric literature comprises more than 500 journals. This paper reviews the
      relative impact of 63 pediatric journals and 26 highly cited journals that also
      publish pediatric articles. Using the objective measures of citation analysis and
      an understanding of the type of literature appropriate for one's purpose of
      study, physicians, scientists and students can avoid the pitfalls of information
      overload created by the proliferation of journals and information technology,
      while effectively extracting the clinical and basic science knowledge that will
      aid their reading and research. As the medical and scientific knowledge database
      continues to grow, knowing where to look for significant articles may likely
      become as important as knowing how to apply the information contained within
      them. Realizing that a significant portion of influential and important articles
      can be found in a relatively small group of journals can guide one's initial
      literature search, but one must also remember that equally valuable information
      can be found in other publications. Armed with the tools to minimize the field of
      less appropriate sources, one can more readily achieve the real purpose of a
      search, which is to uncover the bloom of knowledge and to nurture, cultivate and
      share it.

PMID- 9775491
TI  - Helicobacter pylori infection in children.
AB  - Helicobacter pylori colonises the stomach of man, especially during childhood.
      However, Helicobacter pylori strains are not created equal, with major
      differences in virulence characteristics which probably account for different
      clinical symptoms. The majority of infected subjects remain asymptomatic. H.
      pylori infection is correlated with socioeconomic conditions and hygienic
      circumstances, resulting in an extremely high prevalence in (children of)
      developing countries. Commercial available screening tests are not capable to
      separate the more virulent strains (type I with vacuolating toxin VacA and CagA
      protein) from the less virulent strains (Type II, vacA and CagA negative). Type I
      strains, but not Type II, are associated with an increased risk for duodenal
      ulcer and gastric cancer. Therefore, (future) screening tests (and vaccination)
      should focus on the Type I strains.

PMID- 9775492
TI  - Comparison of the outcome of extremely-low-birth-weight infants between two
      periods.
AB  - A comparison was made of the outcome of 73 neonates born with their birth weight
      of 500-999 gm in National Taiwan University Hospital during the period between
      January 1, 1993 and December 31, 1996 (Period II), with the outcome of 21 such
      neonates born between April 1, 1988 and October 31, 1992 (Period I). Exclusion
      criteria included parental refusal for resuscitation, and major anomalies. Data
      were collected via a predetermined record sheet. The incidences of the extremely
      low-birth-weight infants were 23/10,173 (0.23%) and 81/13,835 (0.59%) in Periods
      I and II, respectively. Early neonatal mortality rate was significant decreased
      in Period II (43% versus 14%). The limit of viability was improved from
      gestational age of 26 weeks or 700 gm to gestational age of 24 weeks or 600 gm.
      The incidence of neonatal morbidity (80% versus 50%) and total survival rate (48%
      versus 60%) have not changed significantly as seen in this limited number of
      cases. This study concluded that, with the introduction of exogenous surfactant
      and modern neonatal care, early neonatal survival rate and the limit of viability
      were improved.

PMID- 9775493
TI  - Home oxygen therapy for chronic lung disease in very low-birth-weight infants.
AB  - Prolonged hospitalization in infants suffering from chronic lung disease who
      require continuous oxygen therapy can be avoided by oxygen administration at
      home. In the period from August 1995 to September 1996, 155 very low-birth-weight
      (VLBW) infants were consecutively admitted to the neonatal intensive care unit of
      Mackay Memorial Hospital. Of the 155 infants, 72% (111/155) survived to
      discharge. However, 34% (38/111) of the survivors developed chronic lung disease.
      Twenty-three infants with chronic lung disease underwent home oxygen therapy
      after 107.0 +/- 43.6 days of hospitalization. The mean duration of home oxygen
      therapy was 4.3 +/- 3.4 months. In the first year after discharge, 91% of the
      patients required rehospitalization. One patient died during the fourth
      hospitalization. Follow-up information on growth and development at one year of
      corrected age was available for 19 patients. Five of the 19 patients had a body
      weight below the 5th percentile. Five of the 19 infants were mentally retarded
      and 12 of the 19 patients had significantly delayed motor development. In
      conclusion, carefully supervised home oxygen therapy permits safe early discharge
      of selected VLBW infants with chronic lung disease. Their somatic and psychomotor
      development should be carefully followed up.

PMID- 9775494
TI  - Strokes in children: a medical center-based study.
AB  - Stroke is an important cause of mortality and morbidity in children. Cases of
      pediatric stroke admitted to National Taiwan University Hospital from January
      1985 to December 1995 were reviewed. Patients whose stroke was obviously caused
      by premature birth, birth trauma or head injury were excluded. Totally 65
      patients were enrolled, including 37 boys and 28 girls. Their ages ranged from
      birth to 18 years old. They were classified into two groups: ischemic stroke (38
      patients) and hemorrhagic stroke (27 patients), according to the pathogenesis.
      The ages of onset, clinical manifestation, underlying diseases and treatment of
      these two groups were systematically analyzed. The major presenting symptoms of
      both ischemic and hemorrhagic strokes were motor deficit (65.8%) and
      consciousness disturbance (55.6%). A wide variety of diseases predisposing to
      strokes was identified. The major causes of hemorrhagic stroke were vascular
      malformation and oncologic conditions, with the latter, the most frequently
      encountered underlying diseases associated with childhood ischemic stroke. The
      mortality rate for hemorrhagic stroke was 37% and, for ischemic stroke, 21.1%.
      There was male predominance in pediatric stroke. Although the clinical symptoms
      and signs might provide some guidelines to differentiate between hemorrhagic and
      ischemic strokes, neuroimaging studies were crucial to more exact diagnosis. A
      variety of diseases may contribute to pediatric stroke. Early diagnosis determine
      treatability, then aggressive treatment are important.

PMID- 9775495
TI  - Immunological studies of children with anaphylactoid purpura.
AB  - Anaphylactoid purpura is a small-vessel, vasculitic disease of unknown etiology,
      but it is thought to be caused by an immunoglobulin-mediated inflammatory
      process. To study the immunological profiles of local anaphylactoid purpura
      patients, during the period from October 1996 to October 1997 with 17 patients,
      (6 boys and 11 girls), (aged 3 years to 17 years, mean age: 7.9 years), with
      anaphylactoid purpura who visited National Taiwan University Hospital.
      Immunological studies were performed in 17 patients and 20 age-matched healthy
      controls. Higher C3 was noted in patients (126.2 +/- 26.7 mg/dL) than in the
      control group (116.1 +/- 16.7 mg/dL), although without statistical significance
      (P = 0.307). C4 levels of patients were significantly higher in patients than
      control group (38.6 +/- 13.4 v.s. 23.7 +/- 6.9 mg/dL), P < 0.001). There were no
      significant differences in the IgG and IgM levels between patient and control
      groups. In contrast, the IgA levels of patient were significantly higher than
      that control groups (293.1 +/- 102.9 v.s. 179.8 +/- 71.0 mg/dL, P = 0.001). The
      serum level of TGF-beta 1 of patients was higher than that of the control group
      although not statistically significant (44.1 +/- 27.3 v.s. 29.9 +/- 19.0 ng/mL, p
      = 0.067). A significantly higher percentage of T cells was noted in anaphylactoid
      purpura patients than controls (71.5 +/- 9.2% v.s. 65.0 +/- 6.3%, P = 0.016).
      However, no significant difference was found in other subpopulations of
      lymphocytes. These basic immunological profiles may be helpful for further work
      on the pathogenesis of anaphylactoid purpura.

PMID- 9775496
TI  - Germ cell tumor in infancy and childhood: experience at one institute compared to
      other studies.
AB  - To understand the difference in incidence and distribution of germ cell tumor
      (GCT) between cases seen in this institute and Western studies, 98 cases of GCTs
      collected from 1979 to 1996 were included 50 with gonadal GCTs, 9 with
      mediastinal GCTs; 9 with retroperitoneal GCTs, 10 with sacrococcygeal GCTs and 20
      with intracranial GCTs; all were analyzed retrospectively by chart review. The
      incidences of testicular and intracranial GCT in all GCTs were higher in this
      study, i.e. 26.5%(26/98) and 20.4%(20/98) compared to 7% and 6% of American
      reports. But the incidence of sacrococcygeal GCT in all GCTs was lower in this
      study, i.e. 10.2%(10/98) compared to 41% of American reports. The incidences of
      testicular and ovarian GCT in all GCTs were about the same in this study, i.e.
      26.5%(26/98) and 24.5%(24/98) compared to 7% and 29% of American reports;
      51%(50/98) of all GCTs were gonadal in this study compared to 36% in the American
      reports.

PMID- 9775497
TI  - Spontaneous resolution of an intratracheal mass: report of one case.
AB  - A 14 year-old boy was investigated for a slowly resolving right upper lobe
      consolidation persisting for 3 months after a pneumonic episode. A flexible
      bronchoscopy showed a polypoid mass in the carina with extension to the right
      proximal bronchus. The bronchial washings study for fungus, acid-fast bacilli and
      polymerase chain reaction for mycobacterium were negative. A reported
      bronchoscopic examination 8 months later revealed no tracheal mass or subsequent
      stenosis. A tracheal mass in an asymptomatic and non-progressive child may be
      managed alternatively by repeated bronchoscopic examinations at intervals instead
      of immediate bronchoscopic excision or thoracotomy.

PMID- 9775498
TI  - Transplantation for adrenoleukodystrophy with HLA-A and B nonidentical paternal
      marrow: report of one case.
AB  - We report the result of allogeneic bone marrow transplantation (BMT) in a 14-year
      old boy who was neurologically severely involved with the childhood form of
      adrenoleukodystrophy (ALD) and received marrow from his HLA-A and B nonidentical,
      MLC-nonreactive paternal donor without T-cell depletion processing. Bone marrow
      transplantation corrected the excess content of very long chain fatty acid in
      plasma but did not arrest the deterioration of the neurological status during 3.5
      year post-transplant follow-up period. Since partially matched or unrelated
      donors have been applied to clinical BMT successfully with current new
      techniques, ALD patients will have a better prognosis when they are transplanted
      in status of mild and early involvement. Our first experience may be helpful in
      more trials of BMT for genetic leukodystrophy in Taiwan.

PMID- 9775499
TI  - Perinatal candidiasis and transient maternal candidemia: report of one case.
AB  - A premature infant who contracted candida pneumonia and candidemia early in the
      postnatal period was reported. Fungal hyphae was found in the pus-like gastric
      aspirate soon after birth, giving the first clue to the diagnosis and prompting
      an early institution of antifungal therapy. Maternal candidemia was documented in
      the immediate postpartum period, which resolved spontaneously without specific
      antifungal treatment.

PMID- 9775500
TI  - Successful treatment of Sjogren's syndrome with cyclophosphamide pulse therapy:
      report of one case.
AB  - The treatment of Sjogren's syndrome (SS) is very controversial, though several
      therapeutic regimens have been proposed. Cyclophosphamide pulse therapy has been
      widely used in many disease entities. However, reports concerning its clinical
      application in SS were very rare. We report a 17-year-old girl presenting with
      lupus nephritis and SS, which was refractory to corticosteroid therapy but
      successfully treated with cyclophosphamide pulse therapy. The improvement of
      clinical features was confirmed by Schirmer's test and minor salivary gland
      biopsy.

PMID- 9775501
TI  - Swyer James syndrome following Mycoplasma pneumoniae pneumonia: report of one
      case.
AB  - A previous healthy 5 year-old girl developed a right hyperlucent lung following
      Mycoplasma pneumoniae pneumonia 14 months before admission. Serial chest
      radiographs revealed a persistent right upper lobe atelectasis and gradual
      development of the right hyperlucent lung associated with frequent bouts of
      wheezing and exertional dyspnea. Physical examination showed markedly decreased
      breathing sounds in the right hemithorax with fine inspiratory crackles and
      expiratory wheezes. A diagnosis of Swyer James syndrome was confirmed by the
      exclusion of other causes of unilateral hyperlucent lung using computed
      tomographic scans of chest, fiberoptic bronchoscopy and lung perfusion
      scintigraphy. She has been followed up at our hospital using anti-asthmatic
      medication.

PMID- 9775502
TI  - Seizures: classification, etiologies, and pathophysiology.
AB  - Epilepsy is a disorder of recurrent seizures that are neural in origin. Partial
      seizures are usually due to a structural cerebrocortical lesion and may be simple
      or complex. Brain injuries may alter inherent neuronal properties and neuronal
      circuits and lead to recurrent excitatory activity. Potentiation of excitatory
      synapses and depression of inhibitory synapses are probable critical events in
      epileptogenesis. The pathogenic factors underlying primary or idiopathic
      generalized seizures are not as well understood. A more diffuse or multifocal
      state of neuronal excitability may be the result of early congenital events that
      are magnified over time. The progression of subclinical neuronal excitatory
      activity to a clinical seizure may relate directly to the phenomenon of cortical
      plasticity.

PMID- 9775503
TI  - Interictal paroxysmal discharges in the electroencephalograms of epileptic dogs.
AB  - Paroxysmal discharges (PD) consisting of spikes, multiple spike complexes, sharp
      waves, multiple sharp-wave complexes, and spike-and-slow-wave complexes can be
      recorded in the interictal electroencephalograms of sedated epileptic dogs. With
      appropriate methods, focal PD can be detected and the hemisphere of origin and
      rostrocaudal location of their sources identified. Electrode montages that permit
      ready recognition of so-called instrumental phase reversal are especially
      helpful. PD that are presumably generalized can be recorded from dogs with
      signalments suggesting inherited/"idiopathic" epilepsy. These PD are described as
      "presumably" generalized because of the lack of recordings from ventral and
      ventrolateral cerebral regions. Further study is necessary, attempting to
      correlate types of PD with types of epilepsy.

PMID- 9775504
TI  - Idiopathic epilepsy.
AB  - Idiopathic epilepsy is one of the most common and treatable neurologic diseases
      of small animals. The objectives of this article are to present a clinical
      overview and practical approach to its management. A review of terminology,
      epidemiologic issues, diagnosis, differential diagnosis, and general principles
      of treatment are presented.

PMID- 9775505
TI  - Feline epilepsy.
AB  - The diagnosis and management of seizures in the cat require an understanding of
      the more common diseases that predispose to feline epilepsy. Feline seizures may
      occur secondary to intracranial or extracranial disease. Intracranial causes
      include inflammatory, neoplastic, vascular, and traumatic disorders. Extracranial
      causes include various metabolic and toxic insults. Previous brain insults that
      are no longer active may leave "seizure foci." Idiopathic epilepsy is uncommon in
      the cat relative to the dog but should be considered if no cause can be found.
      Regardless of the etiology, ictal events in cats can manifest themselves in
      multiple forms and levels of severity. Therapy should be directed at controlling
      seizure frequency and treating the underlying cause. An aggressive diagnostic and
      therapeutic approach to feline epilepsy may improve prognosis and lead to a
      favorable outcome.

PMID- 9775506
TI  - Toxic and metabolic causes of seizures.
AB  - Seizures are a relatively nonspecific response of the cerebral cortex to insult
      and can be caused by a variety of toxic or metabolic diseases. Seizure in
      response to extracranial disease are called reactive seizures. Toxins cause
      seizures by altering the balance of excitation and inhibition in the nervous
      system or interfering with energy metabolism. Many therapeutic or illicit drugs
      will cause seizures through similar mechanisms. Metabolic diseases can cause
      seizures by interfering with energy metabolism, changing osmolality, or producing
      endogenous toxins. In addition, metabolic disease may alter the pharmacokinetics
      of antiepileptic drugs or drugs that have the potential to cause seizures. While
      seizures represent a serious sign for many of these conditions, reactive epilepsy
      always carries the possibility that the seizures may be eliminated if the
      underlying cause is detected and corrected.

PMID- 9775507
TI  - Inflammatory diseases of the central nervous system in dogs.
AB  - Inflammatory diseases of the central nervous system (CNS) are important causes of
      seizures in dogs. Specific diseases include canine distemper, rabies,
      cryptococcosis, coccidioidomycosis, toxoplasmosis, neosporosis, Rocky Mountain
      spotted fever, ehrlichiosis, granulomatous meningoencephalomyelitis, and pug dog
      encephalitis. Inflammatory disorders should be considered when a dog with
      seizures has persistent neurological deficits, suffers an onset of seizures at
      less than 1 or greater than 5 years of age, or exhibits signs of systemic
      illness. A thorough history, examination, and analysis of cerebrospinal fluid are
      important in the diagnosis of inflammatory diseases. However, even with extensive
      diagnostic testing, a specific etiology is identified in less than two thirds of
      dogs with inflammatory diseases of the CNS.

PMID- 9775508
TI  - Seizures as a complication of brain tumors in dogs.
AB  - Seizures are a common reflection of a variety of intracranial physiologic
      abnormalities in dogs. In dogs with brain tumors, seizures often provide the
      clinical clue to the existence of an underlying structural brain disease. The
      majority of brain tumors that result in seizures affect the supratentorial
      nervous system, especially the olfactory and frontal lobes. Diagnosis requires
      advanced imaging such as computed tomography (CT) or magnetic resonance imaging
      (MRI) to establish the presence of a structural abnormality. Therapy is directed
      both at tumor and seizure control to afford the best chance of successful
      management of dogs with brain tumors.

PMID- 9775509
TI  - Antiepileptic drug therapy.
AB  - Successful treatment of seizure disorders in small animals requires proper
      patient assessment, understanding the principles of antiepileptic drug (AED)
      therapy, designing a strategy for pharmacotherapy, and plans for emergency
      treatment. Several levels of assessment are needed in managing an epileptic
      patient to include the diagnosis, effectiveness of therapy, and health-related
      quality of life assessments. Three levels of diagnosis are important in
      determining the appropriate AED therapy: 1) confirmation that an epileptic
      seizure has occurred, and if so, the seizure type(s) manifested; 2) diagnosis of
      the seizure etiology; and 3) determination of an epileptic syndrome. Monotherapy
      is the initial goal of treating any cat or dog with epilepsy to reduce possible
      drug-drug interactions and adverse effects. Unfortunately, many of the AEDs
      useful in people cannot be prescribed to small animals either due to
      inappropriate pharmacokinetics (too rapid of an elimination), and potential
      hepatotoxicity. Thus, the most commonly used AEDs in veterinary medicine are from
      the same mechanistic category, that of enhancing inhibition of the brain.
      Antiepileptic drugs can be classified into three broad mechanistic categories: 1)
      enhancement of inhibitory processes via facilitated action of gamma amino-butyric
      acid (GABA); 2) reduction of excitatory transmission; and 3) modulation of
      membrane cation conductance. Pharmacotherapy strategies should be designed based
      on the decision when to start treatment, choice of the appropriate AED, and
      proper AED monitoring and adjustment. Information is presented for the current
      AEDs of choice, phenobarbital and bromide. Additional guidelines are provided for
      administration of newer AEDs, felbamate and gabapentin. All owners should be
      aware that emergency therapy may be necessary if recurrent or severe seizures
      occur in their pet. A rapid, reliable protocol is presented for the emergency
      management of seizuring cats and dogs in the hospital and at home. Home treatment
      with per rectal administration of diazepam in the dog has proven to be an
      effective means of reducing seizure frequency and owner anxiety. Treating each
      animal as an individual, applying the philosophy that seizure prevention is
      better than intervention, and consulting specialists to help formulate or revise
      treatment plans will lead to improved success in treating seizure disorders in
      the cat and dog.

PMID- 9775510
TI  - How can mental models theory account for content effects in conditional
      reasoning? A developmental perspective.
AB  - This article proposes a modification to Johnson-Laird's mental models theory
      applied to the interpretation of conditional statement of the form 'if ... then'.
      The model suggests that this interpretation is based on the construction of
      mental models supplied by establishing a correspondence between the semantic
      spaces associated with the antecedent and consequent of the statements. The
      construction of the models and the interpretation of the statements would depend
      on the nature of the semantic spaces involved, the interpretative context and the
      subject's knowledge and processing capacity. Three experiments show that the
      interpretation of conditional rules depends, for example, on whether or not the
      conditional rule possess binary terms (e.g. boy/girl). The developmental approach
      makes it possible to reveal phenomena which tend to remain hidden in studies of
      adult functioning. We show that the model accounts for a number of the reasoning
      biases described in the literature as well as for the interpretation of various
      conditional forms which do not have a truth-functional meaning.

PMID- 9775511
TI  - Predictive action in infancy: tracking and reaching for moving objects.
AB  - Because action plans must anticipate the states of the world which will be
      obtained when the actions take place, effective actions depend on predictions.
      The present experiments begin to explore the principles underlying early
      developing predictions of object motion, by focusing on 6-month-old infants' head
      tracking and reaching for moving objects. Infants were presented with an object
      that moved into reaching space on four trajectories: two linear trajectories that
      intersected at the center of a display and two trajectories containing a sudden
      turn at the point of intersection. In two studies, infants' tracking and reaching
      provided evidence for an extrapolation of the object motion on linear paths, in
      accord with the principle of inertia. This tendency was remarkably resistant to
      counter-evidence, for it was observed even after repeated presentations of an
      object that violated the principle of inertia by spontaneously stopping and then
      moving in a new direction. In contrast to the present findings, infants fail to
      extrapolate linear object motion in preferential looking experiments, suggesting
      that early-developing knowledge of object motion, like mature knowledge, is
      embedded in multiple systems of representation.

PMID- 9775512
TI  - Children's mental representation of referential relations.
AB  - We identify a surprising discrepancy in children's performance in two tasks which
      appear superficially to require handling of the same properties of the
      representational mind. Four- to six-year-olds made judgements about the knowledge
      of a protagonist who had only partial information about an object: the child knew
      that an object in a box had two descriptions, X and Y (e.g. dice and eraser), but
      the protagonist had access to only one of these, X. In Experiment 1, children who
      passed a standard false-belief task also judged correctly that the protagonist
      did not know the X was Y, but often judged wrongly that he did know there was a Y
      in the box. In Experiment 2, children predicted wrongly where the protagonist
      would look for a Y: the problem was not purely linguistic. We argue that success
      on standard theory-of-mind tasks can be supported by a more basic representing
      ability than is assumed in current theories, and that children's mental
      representation of referential relations between the world and the mind
      subsequently undergoes important change.

PMID- 9775513
TI  - The development of calibration-based reasoning about collision events in young
      infants.
AB  - Previous research indicates that, when shown a collision between a moving and a
      stationary object, 11-month-old infants believe that the size of the moving
      object affects how far the stationary object is displaced. The present
      experiments examined whether 6.5- and 5.5-month-old infants hold the same belief.
      The infants sat in front of a horizontal track; to the left of the track was an
      inclined ramp. A wheeled toy bug rested on the track at the bottom of the ramp.
      The infants were habituated to an event in which a medium-size cylinder rolled
      down the ramp and hit the bug, propelling it to the middle of the track. Next,
      the infants saw two test events in which novel cylinders propelled the bug to the
      end of the track. The two novel cylinders were identical to the habituation
      cylinder in material but not in size: one was larger (large-cylinder event) and
      one was smaller (small-cylinder event) than the habituation cylinder. The 6.5
      month-old infants, and the 5.5-month-old female infants, looked reliably longer
      at the small- than at the large-cylinder event. These and control results
      indicated that the infants (a) believed that the size of the cylinder affected
      the length of the bug's trajectory and (b) used the habituation event to
      calibrate their predictions about the test events. Unlike the other infants, the
      5.5-month-old male infants tended to look equally at the small- and large
      cylinder events. Further results indicated that this negative finding was not due
      to the infants' (a) failure to remember how far the bug rolled in the habituation
      event or (b) inability to use the habituation event to calibrate predictions
      about novel test events. Together, the present results suggest the following
      conclusions. First, when shown a collision between a moving and a stationary
      object, infants aged 5.5-6.5 months (a) believe that there is a proportional
      relation between the size of the moving object and the distance traveled by the
      stationary object and (b) can engage in calibration-based reasoning about this
      size/distance relation. Second, female infants precede males by a few weeks in
      this development, for reasons that may be related to sex differences in the
      maturation of depth perception.

PMID- 9775514
TI  - Linguistic influences in cognitive arithmetic: comment on Noel, Fias and
      Brsybaert (1997)
AB  - Noel et al. (Noel, M.-P., Fias, W., Brsybaert, M., 1997. About the influence of
      the presentation format on arithmetical-fact retrieval processes. Cognition 63,
      335-374) examined the simple-multiplication errors of 24 Dutch- and 24 French
      speaking adults for evidence that number reading interferes with language
      specific, number-fact retrieval processes. They concluded that arithmetic memory
      is not influenced by reading-based interference and is based on a notation and
      language-independent mental representation. Alternative analyses of their error
      data, however, provide strong evidence that arithmetic performance is subject to
      reading-based interference and provide some support for the language-specificity
      of number-fact memory.

PMID- 9775515
TI  - Does language really matter when doing arithmetic? Reply to Campbell (1998)
AB  - Campbell (1998) has questioned the conclusion of Noel et al. (1997) and has
      argued that alternative analyses of their data provide strong evidence that
      arithmetic performance is subject to reading-based interference and provide some
      support for the language-specificity of number-fact memory. We consider that
      Campbell reached conclusions different from those we had obtained because (1) he
      performed his analyses on a different data set (i.e. including also the table
      unrelated errors), (2) he has given a double weight to the naming errors and (3)
      he has multiplied the analyses without correcting the corresponding P values. We
      thus consider that there exist interactions between language and performance in
      simple multiplication tasks, but that the current data can easily be explained
      without postulating that such interactions operate at the level of the retrieval
      stage. In other words, we consider that there are not definitive arguments, as
      yet, in favour of the hypothesis of modality-specific arithmetical-fact networks.

PMID- 9775516
TI  - Linguistic complexity: locality of syntactic dependencies.
AB  - This paper proposes a new theory of the relationship between the sentence
      processing mechanism and the available computational resources. This theory--the
      Syntactic Prediction Locality Theory (SPLT)--has two components: an integration
      cost component and a component for the memory cost associated with keeping track
      of obligatory syntactic requirements. Memory cost is hypothesized to be
      quantified in terms of the number of syntactic categories that are necessary to
      complete the current input string as a grammatical sentence. Furthermore, in
      accordance with results from the working memory literature both memory cost and
      integration cost are hypothesized to be heavily influenced by locality (1) the
      longer a predicted category must be kept in memory before the prediction is
      satisfied, the greater is the cost for maintaining that prediction; and (2) the
      greater the distance between an incoming word and the most local head or
      dependent to which it attaches, the greater the integration cost. The SPLT is
      shown to explain a wide range of processing complexity phenomena not previously
      accounted for under a single theory, including (1) the lower complexity of
      subject-extracted relative clauses compared to object-extracted relative clauses,
      (2) numerous processing overload effects across languages, including the
      unacceptability of multiply center-embedded structures, (3) the lower complexity
      of cross-serial dependencies relative to center-embedded dependencies, (4)
      heaviness effects, such that sentences are easier to understand when larger
      phrases are placed later and (5) numerous ambiguity effects, such as those which
      have been argued to be evidence for the Active Filler Hypothesis.

PMID- 9775517
TI  - Motor processes in mental rotation.
AB  - Much indirect evidence supports the hypothesis that transformations of mental
      images are at least in part guided by motor processes, even in the case of images
      of abstract objects rather than of body parts. For example, rotation may be
      guided by processes that also prime one to see results of a specific motor
      action. We directly test the hypothesis by means of a dual-task paradigm in which
      subjects perform the Cooper-Shepard mental rotation task while executing an
      unseen motor rotation in a given direction and at a previously-learned speed.
      Four results support the inference that mental rotation relies on motor
      processes. First, motor rotation that is compatible with mental rotation results
      in faster times and fewer errors in the imagery task than when the two rotations
      are incompatible. Second, the angle through which subjects rotate their mental
      images, and the angle through which they rotate a joystick handle are correlated,
      but only if the directions of the two rotations are compatible. Third, motor
      rotation modifies the classical inverted V-shaped mental rotation response time
      function, favoring the direction of the motor rotation; indeed, in some cases
      motor rotation even shifts the location of the minimum of this curve in the
      direction of the motor rotation. Fourth, the preceding effect is sensitive not
      only to the direction of the motor rotation, but also to the motor speed. A
      change in the speed of motor rotation can correspondingly slow down or speed up
      the mental rotation.

PMID- 9775518
TI  - The effect of face inversion on the human fusiform face area.
AB  - Inversion severely impairs the recognition of greyscale faces and the ability to
      see the stimulus as a face in two-tone Mooney images. We used functional magnetic
      resonance imaging to study the effect of face inversion on the human fusiform
      face area (FFA). MR signal intensity from the FFA was reduced when greyscale
      faces were presented upside-down, but this effect was small and inconsistent
      across subjects when subjects were required to attend to both upright and
      inverted faces. However when two-tone faces were inverted, the MR signal from the
      FFA was substantially reduced for all subjects. We conclude that (i) the FFA
      responds to faces per se, rather than to the low-level visual features present in
      faces, and (ii) inverted greyscale faces can strongly activate this face-specific
      mechanism.

PMID- 9775519
TI  - Separating hierarchical relations and word order in language production: is
      proximity concord syntactic or linear?
AB  - In this paper we address the question whether hierarchical relations and word
      order can be separated in sentence production. In two experiments, we assess
      whether subject-verb agreement errors (such as 'The time for fun and games are
      over') require linear proximity of a so-called 'local' noun ('games' in the
      example) to the verb. In the first experiment, we found a proximity effect when
      participants were asked to complete sentential beginnings of the kind: 'The
      helicopter for the flights'. In the second experiment, we asked participants to
      produce a question such as 'Is the helicopter for the flights safe?'. The
      syntactic relation between the subject noun and the local noun is the same in the
      two experiments, but the linear position of the local noun is different. The
      distribution of agreement errors was similar in the two experiments. We argue
      that these data provide evidence for a stage in language production in which a
      syntactic structure is built prior to a stage in which words are assigned to
      their linear position. Agreement is computed during the first stage.

PMID- 9775520
TI  - Tuberculosis notifications in Australia, 1996. Communicable Diseases Network
      Australia New Zealand.
AB  - Since the implementation of the National Mycobacterial Surveillance System (NMSS)
      in 1991, the epidemiology and trends of tuberculosis in Australia have been
      described in a series of annual reports. This article presents an analysis of the
      data for tuberculosis notifications for 1996. A total of 1,037 notifications of
      tuberculosis were received for the year 1996, and the crude rates of new and
      relapsed disease were reported at 5.37 per 100,000 and 0.29 per 100,000
      respectively. Rates of tuberculosis have remained stable over the last decade and
      the majority of notifications and highest rates of disease continue to occur in
      the overseas-born population.

PMID- 9775521
TI  - Tuberculosis in Australia: bacteriologically confirmed cases and drug resistance,
      1996. Report of the Australian Mycobacterium Reference Laboratory Network.
AB  - The Australian Mycobacterium Reference Laboratory Network collected and analysed
      laboratory data on new diagnoses of infection with Mycobacterium tuberculosis
      complex during 1996. A total of 750 cases were identified, representing an annual
      incidence of 4.1 cases of laboratory confirmed tuberculosis per 100,000
      population. The incidence rate varied between States, reflecting differences in
      the distribution of persons belonging to 'high-risk' categories for tuberculosis.
      Incidence statistics were almost identical to those recorded by the Network in
      1994 and 1995. The male:female ratio remained at around 1.2:1. As was the case in
      1995, the median age group for males was 45-49 years and for females 35-39 years.
      The frequency of positive microscopy in pulmonary samples was stable at around
      55%. Lymphatic disease accounted for 19% of the total cases in 1996 compared with
      15% in the previous year, confirming that lymphadenitis is becoming more common
      in females with tuberculosis in Australia. Approximately 11% of isolates had in
      vitro resistance to at least one of the four standard anti-tuberculosis drugs, an
      increase from 8% in 1994-95. Fifteen isolates were multi-drug resistant, compared
      with a total of only 38 during the previous seven years. Thus, the 1996 data
      points to an increasing frequency of multi-drug resistant strains among isolates
      from Australian patients with tuberculosis.

PMID- 9775522
TI  - A case of diphtheria in New Zealand.

PMID- 9775524
TI  - How long should you boil water to make it safe to drink?

PMID- 9775525
TI  - Communicable diseases surveillance.

PMID- 9775523
TI  - Sporadic human anthrax in urban Brisbane.

PMID- 9775526
TI  - Meningeal enhancement surrounding meningiomas on Gd-DTPA MRI.
AB  - Meningeal enhancement (ME) using Gd-DTPA MRI was studied in 25 of 35 patients
      with meningiomas, and its clinical importance on associated MRI and histologic
      findings of ME was evaluated. ME extended 0.5-4.3 cm (mean: 1.5 cm) from the
      tumor attachment site, and was classified morphologically into two patterns: that
      extending with a gentle curve from the tumor attachment site to the dura, and
      that extending linearly. Tumor parenchyma was differentiated from ME based on
      time-dependent changes in signal intensity on Gd-DTPA MRI. Histologic examination
      was performed in tissue from regions of ME of 15 patients. Tissue corresponding
      to regions of ME consisted of two layers: an outer dura mater layer and an inner
      layer of hyperplasic loose fibrous tissue with dilated capillaries. Meningeal
      tumor cell clusters were observed in the fibrous tissue of 4 patients. These
      clusters were observed at a maximum distance of 1.4 cm from the tumor attachment
      site. It is thought that meningeal tumor cell clusters may represent a potential
      cause of local recurrence. Therefore, resection of the dura at least 2 cm from
      the tumor attachment site may be required to prevent local recurrence.

PMID- 9775527
TI  - Clinicopathologic features of local and metastatic recurrences in primary lung
      adenocarcinoma.
AB  - We attempted to construct the contour of recurrence in primary lung
      adenocarcinoma with clinicopathologic variables based on data of 131 patients
      with completely resected primary lung adenocarcinoma. In univariate analysis,
      tumor size (more or less 3 cm in diameter), p-T, p-N, pathological stage,
      differentiation, ly factor and v factor were chosen for prognostic predictors. In
      multivariate analysis, v factor and p-N were independent variables of local
      recurrence and metastatic recurrence, respectively. The examination of
      significant correlation among clinicopathologic variables in terms of 5-year
      survival rates of patients showed that tumor size, p-T, ly factor and v factor
      were profoundly related to local recurrence, whereas ly factor, differentiation
      and p-N were linked to distant metastasis. We therefore examined an additive
      effect of tumor size, differentiation and vascular invasion on recurrence. The
      results demonstrated that neither local nor metastatic recurrences were found in
      patients with well differentiated adenocarcinoma less than 3 cm in diameter if
      vascular invasion was negative. We conclude that vascular (ly factor and v
      factor) is central to lung adenocarcinoma recurrence. The vascular invasion is a
      powerful predictor of recurrence in less than 3 cm diameter, well differentiated
      adenocarcinoma of the lung.

PMID- 9775528
TI  - Contribution of endothelium in contractile response of isolated rabbit aortic
      preparation to electrical field stimulation.
AB  - An isolated rabbit aortic preparation, on which drugs selectively act from the
      intimal surface was made. The contractile response of the aortic preparation to
      norepinephrine (NE) (1 nM-10 microM) administered from the intimal surface was
      considerably reduced by removal of the endothelium, whereas the response to KCl
      was not changed. The contractile response of the aortic preparation to electrical
      field stimulation (EFS) was abolished by the treatment with tetrodotoxin (1
      microM), guanethidine (1 microM) or prazosin (10 microM), indicating that the
      response was elicited by the release of NE from the adrenergic nerve terminals.
      The contractile response of the aortic preparation to EFS was also considerably
      reduced by the removal of the endothelium. A nitric oxide (NO) synthase
      inhibitor, NG-nitro-L-arginine (100 microM) had almost no effect on the
      contractile response to EFS, indicating that the involvement of NO in the
      contractile response was negligible. In prostaglandin F2 alpha (PGF 2 alpha)
      contracted aortic preparation, the contractile response to EFS was never
      converted into relaxing response by the treatment with prazosin (10 microM). The
      finding confirmed that adrenergic beta action of NE released from nerve terminals
      on the aorta was minor. These findings indicate that endogenously released NE
      from adrenergic nerve terminals as well as exogenously administered NE acts on
      the endothelium and may release endothelium derived contracting factor(s) which
      act together with NE on the vascular smooth muscle.

PMID- 9775529
TI  - Clinical characteristics of breast cancer patients with family history.
AB  - This study was conducted to acquire information as to the clinicopathological
      characteristics of breast cancer patients with family history. Of 583 patients
      with breast cancer, 60 (10.3%) had family history in at least one relative within
      the second-degree. The affected family member was most frequently a sister (43%),
      followed by the mother (23%) and an aunt (20%). Comparison of the data for the
      patients between with and without family history revealed no significant
      differences for any of mean age, menopausal status, histological type,
      histological staging, and estrogen receptor status. Although the sample size was
      small, neither the survival rate nor the bilaterality of disease was influenced
      by the family history of breast cancer.

PMID- 9775530
TI  - Effect of growth factors on expression of integrin subtypes in microvascular
      endothelial cells isolated from bovine retinas.
AB  - We isolated microvascular endothelial cells from bovine retinas (BREC) by a
      colony isolation method, and investigated the effects of basic fibroblast growth
      factor (bFGF) and vascular endothelial growth factor (VEGF) on growth as well as
      integrin subtype expression of the cultured BREC. Either of the growth factors
      stimulated growth of the cultured BREC. In non-stimulated BREC, alpha v beta 3
      integrin expression was predominant over the other integrin subtypes tested
      (alpha v beta 5, alpha 2 beta 1 and alpha 5 beta 1), but no enhancement of the
      alpha v beta 3 expression occurred by either growth factor stimulation. On the
      other hand, bFGF addition stimulated alpha v beta 5 and alpha 5 beta 1 expression
      while VEGF induced the alpha 2 beta 1 expression as well. These results suggest
      that external stimuli such as bFGF and VEGF alter integrin expression profiles of
      BREC and probably influence interactions of endothelial cells with extracellular
      matrix during angiogenesis which must be involved in pathogenesis of ischemic
      retinal disorders. In this respect, this BREC culture system could be useful to
      study the mechanism of neovascularization in these disorders.

PMID- 9775532
TI  - Time to publication: status.

PMID- 9775531
TI  - Mesenteric venous thrombosis: a case report.
AB  - We describe herein a 41-year-old man who complained of abdominal pain. He
      underwent surgery, and the diagnosis of mesenteric venous thrombosis was made.
      The small intestine, mainly the jejunum, presented necrosis on laparotomy, and a
      155-cm long segment of it was successfully resected. Anticoagulant therapy was
      initiated postoperatively, and he is well at present.

PMID- 9775534
TI  - Forecasting generalized epileptic seizures from the EEG signal by wavelet
      analysis and dynamic unsupervised fuzzy clustering.
AB  - Dynamic state recognition and event-prediction are fundamental tasks in
      biomedical signal processing. We present a new, electroencephalogram (EEG)-based,
      brain-state identification method which could form the basis for forecasting a
      generalized epileptic seizure. The method relies on the existence in the EEG of a
      preseizure state, with extractable unique features, a priori undefined. We
      exposed 25 rats to hyperbaric oxygen until the appearance of a generalized EEG
      seizure. EEG segments from the preexposure, early exposure, and the period up to
      and including the seizure were processed by the fast wavelet transform. Features
      extracted from the wavelet coefficients were imputed to the unsupervised optimal
      fuzzy clustering (UOFC) algorithm. The UOFC is useful for classifying similar
      discontinuous temporal patterns in the semistationary EEG to a set of clusters
      which may represent brain-states. The unsupervised selection of the number of
      cluster overcomes the a priori unknown and variable number of states. The usually
      vague brain state transitions are naturally treated by assigning each temporal
      pattern to one or more fuzzy clusters. The classification succeeded in
      identifying several, behavior-backed, EEG states such as sleep, resting, alert
      and active wakefulness, as well as the seizure. In 16 instances a preseizure
      state, lasting between 0.7 and 4 min was defined. Considerable individual
      variability in the number and characteristics of the clusters may postpone the
      realization of an early universal epilepsy warning. University may not be crucial
      if using a dynamic version of the UOFC which has been taught the individual's
      normal vocabulary of EEG states and can be expected to detect unspecified new
      states.

PMID- 9775533
TI  - A muscular fatigue index based on the relationships between superimposed M wave
      and preceding background activity.
AB  - A practical muscle fatigue index is studied in this paper using the correlation
      between the instantaneous frequencies (IF's) of the superimposed M wave and the
      mean power frequency (MPF) of the preceding background activity. A superimposed M
      wave is an M wave elicited during a sustained contraction and was recently
      introduced for studying muscle fatigue. We investigated the details of the
      distribution of a feature vector (mpf, if) in two-dimensional space. Our
      experimental results showed that MPF and IF's were closely correlated during the
      first phase of a short-term high-level sustained voluntary contraction and then
      became uncorrelated or sometimes showed negative correlation as muscular fatigue
      progressed. Combining the correlation coefficients and conventional myoelectric
      (ME) parameters, such as the MPF and the average rectified value of ME signals,
      we propose a fuzzy rule based muscular fatigue index that can be used for
      managing the inevitable variability among individual subjects collected as a
      group. Introducing fuzzy inference seemed effective, but further studies
      including detailed investigation of the level of voluntary effort, the muscle
      fiber type composition, and metabolic by-products will be needed to customize the
      membership functions and fuzzy rules more appropriately in each practical field.

PMID- 9775535
TI  - Baseband velocity estimation for second-harmonic signals exploiting the
      invariance of the Doppler equation.
AB  - All Doppler systems, whether conventional Doppler domain or radio frequency (RF)
      processing is employed, relate the temporal frequency characteristics of the
      signal at a certain point in depth as function of time to the spatial frequency
      characteristics of the received signal as function of depth. The mean frequency
      of the latter may change as a result of depth-dependent attenuation, nonlinear
      scattering mechanisms, as in harmonic imaging of ultrasound contrast agents, or
      RF signal demodulation. For all these cases, the relationship between spatial and
      temporal mean frequency and target velocity is still governed by the familiar
      Doppler expression if the signal modifications have been properly accounted for.
      A major drawback of RF signal processing to extract the target velocity is the
      large number of data points to consider. The computational complexity increases
      further for harmonic imaging. It is shown conceptually, and demonstrated by
      signal simulations, that prior to velocity estimation RF demodulation followed by
      decimation 1) does not affect the Doppler equation, 2) enhances the information
      content of the samples, 3) reduces the computational load by a factor of four and
      for harmonic signals by a higher factor, and 4) while demodulation does not have
      to be actually performed, but can be accounted for by a scaling factor in the
      cross-correlation function. It is concluded that decimation hardly affects the
      precision of the velocity estimate if possible frequency aliasing is maintained
      within bounds, suggesting that the decimation factor is not critical.

PMID- 9775536
TI  - Nonlinear mechanics of the organ of Corti caused by Deiters cells.
AB  - Though the organ of Corti (OC) has been an object of experimental and theoretical
      hearing research, open questions remain concerning the processing of acoustic
      signals by the cochlea where the OC is located. Today there is extensive
      knowledge about single parts of the organ but a lack of understanding as to how
      these elements act together. One of the reasons for this is the missing analysis
      of the mechanics of the OC in three dimensions. In order to fill this gap, we
      have analyzed a short section (0.06 mm) of the basilar membrane including the OC
      and evaluated its nonlinear finite element model numerically. The Deiters cells
      are idealized as thin elastic beams with a comparably low modulus of elasticity
      of actin. Therefore, they show nonlinear mechanical behavior generating
      additional frequency components with two-tone stimulation.

PMID- 9775537
TI  - Phenomenological evolution equations for heat-induced shrinkage of a collagenous
      tissue.
AB  - Optimization of clinical heat treatments for various pathologies requires
      accurate numerical modeling of the heat transfer, evolution of thermal damage,
      and associated changes in the material properties of the tissues. This paper
      presents two phenomenological equations that quantify time-dependent thermal
      damage in a uniaxial collagenous tissue. Specifically, an empirical rule-of
      mixtures model is shown to describe well heat-induced axial shrinkage (a measure
      of underlying denaturation) in chordae tendineae which results from a spectrum of
      thermomechanical loading histories. Likewise an exponential decay model is shown
      to describe well the partial recovery (e.g., renaturation) of chordae when it is
      returned to body temperature following heating. Together these models provide the
      first quantitative descriptors of the evolution of heat-induced damage and
      subsequent recovery in collagen. Such descriptors are fundamental to numerical
      analyses of many heat treatments because of the prevalence of collagen in many
      tissues and organs.

PMID- 9775538
TI  - Variational formulation of open-ended coaxial line in contact with layered
      biological medium.
AB  - An open-ended coaxial probe designed to measure layered biological media is
      analyzed with a new method. The probe is considered as an electrostatic circuit
      element whose capacitance is solved using a stationary functional. The
      fundamental transverse electric and magnetic field (TEM)-mode and the series of
      evanescent wavemodes in the coaxial cable are used as basis functions. The field
      outside the probe is solved using a Hankel transform. The capacitance is
      calculated for homogeneous materials and two-layer structures and the results are
      compared with values measured with a phantom model. The method can be easily
      extended for structures with an arbitrary number of layers. A practical
      approximation for two-layer cases, originally developed to take into account the
      effect of subcutaneous fat in skin measurements, is presented and its validity
      for different combinations of dielectric constants and the thickness of the first
      layer is demonstrated. The static approximation limits the frequency range, but
      it covers biological measurements up to 500 MHz. The developed method is accurate
      and easy to adopt in practice.

PMID- 9775539
TI  - Frequency series expansion of an explicit solution for a dipole inside a
      conducting sphere at low frequency.
AB  - The electromagnetic field generated by a current dipole situated at an arbitrary
      position inside a conducting sphere is derived using the expansions of the
      spherical vector wave functions. The first few terms in a series expansion of
      this field with respect to the frequency are given for the normal magnetic field
      (used in magnetoencephalogram) and the tangential electric field (used in
      electroencephalogram) outside the conducting sphere at low frequency. It is shown
      that the first correction term to the static solution is linear in the frequency
      omega (the second correction term is proportional to omega 3/2) and, thus, the
      static solution can be used as a good approximation for the solution at a very
      low frequency.

PMID- 9775540
TI  - Modeling assemblies of biological cells exposed to electric fields.
AB  - Gap junctions are channels through the cell membrane that electrically connect
      the interiors of neighboring cells. Most cells are connected by gap junctions,
      and gaps play an important role in local intercellular communication by allowing
      for the exchange of certain substances between cells. Gap communication has been
      observed to change when cells are exposed to electromagnetic (EM) fields. In this
      work, we examine the behavior of cells connected by gap junctions when exposed to
      electric fields, in order to better understand the influence of the presence of
      gap junctions on cell behavior. This may provide insights into the interactions
      between biological cells and weak, low-frequency EM fields. Specifically, we
      model gaps in greater detail than is usually the case, and use the finite element
      method (FEM) to solve the resulting geometrically complex cell models. The
      responses of gap-connected cell configurations to both dc and time harmonic
      fields are investigated and compared with those of similarly shaped (equivalent)
      cells. To further assess the influence of the gap junctions, properties such as
      gap size, shape, and conductivity are varied. Our findings indicate that simple
      models, such as equivalent cells, are sufficient for describing the behavior of
      small gap-connected cell configurations exposed to dc electric fields. With
      larger configurations, some adjustments to the simple models are necessary to
      account for the presence of the gaps. The gap junctions complicate the frequency
      behavior of gap-connected cell assemblies. An equivalent cell exhibits low-pass
      behavior. Gaps effectively add a bandstop filter in series with the low-pass
      behavior, thus lowering the relaxation frequency. The characteristics of this
      bandstop filter change with changes to gap properties. Comparison of the FEM
      results to those obtained with simple models indicates that more complex models
      are required to represent gap-connected cells.

PMID- 9775541
TI  - In vivo Doppler shift measurements using multimode fiber-optic catheters.
AB  - A new fiber-optic catheter for in vivo blood-flow measurements has been
      developed. The catheter is designed to measure blood flow in both the forward
      (toward the catheter tip) and reverse (away from the catheter tip) flow
      directions. It consists of two multimode optical fibers with core diameter of 50
      microns and cladding diameter of 125 microns. One fiber transmits the laser beam
      into blood and the other receives the backscattered light from the erythrocytes
      within the probe volume. In the flow experiment, it was found that the flow
      within the boundary layer is indeed laminar and, hence, the relationship between
      the Doppler shift frequencies and the flow velocities is linear, thereby making
      the linear calibration possible for predicting the free stream flow velocity.
      Plots of the maximum shift frequency (frequency at which the Doppler spectrum
      disappeared into the noise spectrum) against the flow velocities are found to be
      more linear in both the forward and reverse flow directions than that of the
      dominant shift frequency (frequency with the highest amplitude). These results
      were reaffirmed by the numerical flow simulation along the catheter side wall.

PMID- 9775542
TI  - A real-time experimental prototype for enhancement of vision rehabilitation using
      auditory substitution.
AB  - The rehabilitation of blindness, using noninvasive methods, requires sensory
      substitution. A theoretical frame for sensory substitution has been proposed
      which consists of a model of the deprived sensory system connected to an inverse
      model of the substitutive sensory system. This paper addresses the feasibility of
      this conceptual model in the case of auditory substitution, and its
      implementation as a rough model of the retina connected to an inverse linear
      model of the cochlea. We have developed an experimental prototype. It aims at
      allowing optimization of the sensory substitution process. This prototype is
      based on a personal computer which is connected to a miniature head-fixed video
      camera and to headphones. A visual scene is captured. Image processing achieves
      edge detection and graded resolution. Each picture element (pixel) of the
      processed image is assigned a sinusoidal tone; weighted summation of these
      sinewaves builds up a complex auditory signal which is transduced by the
      headphones. On-line selection of various parameters and real-time functioning of
      the device allow optimization of parameters during psychophysical
      experimentations. Assessment of this implementation has been initiated, and has
      so far demonstrated prototype usefulness for pattern recognition. An integrated
      circuit of this system is to be developed.

PMID- 9775543
TI  - Comments on "Hall effect imaging".

PMID- 9775544
TI  - NDs should be future coordinators of health care.

PMID- 9775545
TI  - ND model is the future.

PMID- 9775546
TI  - Clarification about nursing in Russia.

PMID- 9775547
TI  - Nurses should take the high road to serve public need.

PMID- 9775548
TI  - Nursing history: repositories and the Web.

PMID- 9775549
TI  - New definition for nursing informatics needed.

PMID- 9775550
TI  - Nursing research and priorities in Africa, Asia, and Europe.

PMID- 9775551
TI  - Financing, demographic, and political problems confronting Medicare in the United
      States.

PMID- 9775552
TI  - Racial and gender differences in quality of life following kidney
      transplantation.
AB  - PURPOSE: To determine if race or gender affected changes in quality of life (QoL)
      reported by nondiabetic kidney transplant recipients from pre- to 6 and 12 months
      post-transplant and offer possible explanations. Information gained may offer
      direction for interventions designed to enhance post-transplant QoL for patients
      who may be less likely to attain improved outcomes. DESIGN: Descriptive,
      prospective clinical study. A convenience sample of 90 male and female Caucasian
      American and African-American patients was used. Patients were 19 to 67 years of
      age, nondiabetic, and undergoing kidney transplantation at one university
      hospital located in the southern United States. Data were collected 1990 to 1995.
      METHODS: Three questionnaires measuring QoL were used: the Sickness Impact
      Profile, Ferrans and Powers' Quality of Life Index, and the Adult Self-Image
      Scales. Patients completed questionnaires at the time of transplant and at their
      routine 6- and 12-month post-transplant evaluation visits. Repeated measures
      analysis of variance with multiple pre-planned comparisons of least-squares (LS)
      means were performed to determine if differences existed between and within study
      groups over time. FINDINGS: African-Americans achieved less improvement than
      Caucasian-Americans in affective as well as functional measures of QoL. Women
      scored consistently lower than men on most QoL measures at baseline and reported
      greater improvement in functional ability while perceptions of self-image
      remained low. CONCLUSIONS: Although transplantation dramatically improves QoL,
      some segments of the patient population, namely African-Americans and women, do
      not benefit to the same extent as others. Nurses need to recognize sociocultural
      differences in patients and how these differences affect care requirements.

PMID- 9775553
TI  - Postpartum onset of panic disorder.
AB  - PURPOSE: To describe the experience of panic disorder in mothers during the
      postpartum period. The onset of panic disorder during the postpartum period has
      recently been reported. Clinicians are urged to differentiate between the more
      widely known presentation of postpartum depression and the newly reported
      postpartum panic disorder. DESIGN: Phenomenology. The purposive sample consisted
      of six women with panic disorder during the postpartum period. METHODS: In 1995,
      mothers were interviewed regarding their experiences with panic. The verbatim
      transcripts of these interviews were analyzed using Colaizzi's phenomenological
      method. In all, 214 statements regarding mothers' experiences of panic were
      extracted and clustered into six themes. FINDINGS: Panic during the postpartum
      period seriously complicated mothers' lives as they struggled to maintain their
      composure during panic attacks. As a result of recurring panic attacks, negative
      changes in women's lifestyles ensued stripping them of their self-esteem and
      leaving them to bear the burden of disappointing not only themselves, but also
      their families. CLINICAL IMPLICATIONS: Implications for nursing practice with
      mothers suffering from postpartum onset of panic disorder can be derived from
      each one of the six themes. Nurses can help women identify panic triggers to help
      prevent further panic attacks. Also, nursing interventions can target the guilt
      mothers experience over repeatedly disappointing themselves and their families.

PMID- 9775554
TI  - Expert nursing knowledge in the care of patients at risk of impaired swallowing.
AB  - PURPOSE: To describe the practical knowledge of expert nurses when they assess
      and feed patients at risk of impaired swallowing. Observation uncovered a lack of
      well-developed nursing practices in assessing patients' swallowing and eating,
      and a wide range of interventions in the care of difficult-to-feed-patients.
      Finding little previous nursing research to guide practice for patients with
      impaired swallowing, the authors undertook a study to identify and describe the
      knowledge embedded in the everyday practice of nurses. DESIGN: Descriptive,
      exploratory using purposive sampling. Twelve nurses were identified in 1994 as
      expert in the care of patients at risk of impaired swallowing in one Boston,
      Massachusetts teaching hospital. METHODS: Data were collected using written
      narratives by each participant; group interviews in which nurses discussed the
      written narratives; nonparticipant observations and individual interviews of the
      expert nurses; and patients' chart review. Data were analyzed using interpretive
      phenomenology. FINDINGS: Most nurses in the study did not perform a complete
      assessment of swallowing before feeding their patients. Yet, through feeding
      patients, they were able to describe several components of the swallowing
      assessment used in their practice. CONCLUSIONS: The areas of assessment described
      by the nurses can serve as a template for the development of educational content
      and assessment tools for swallowing.

PMID- 9775555
TI  - Quotation and reference accuracy of three nursing journals.
AB  - PURPOSE: To determine the accuracy of bibliographic citations in three widely
      circulated nursing journals, RN, Nursing Management, and Image: Journal of
      Nursing Scholarship. Accurate citations facilitate retrieval of the cited
      documents and establish the judgment and credibility of authors. DESIGN:
      Descriptive, comparative. METHODS: A random sample of 60 references per journal
      published July 1995 to June 1996 was reviewed for citation and quotation
      accuracy. Errors were classified as major or minor. Data were analyzed using the
      SAS statistical package. FINDINGS: Of the 180 references, 58 (32%) had citation
      errors, with 43 of 58 errors classified as major errors, which made retrieval of
      the cited work difficult; 12 of the 180 articles contained a major quotation
      error, including four instances where the content of the original article
      contradicted or was unrelated to the author's contention. CONCLUSIONS: The rate
      of citation and quotation errors in the three sampled nursing journals is
      comparable to rates previously reported for medical and nursing journals. Errors
      of citation and quotation diminish the value of published papers.

PMID- 9775556
TI  - Making do with fewer nurses in the United States, 1945-1965.
AB  - PURPOSE: To analyze the perceptions that nurses and hospital administrators had
      about the nursing shortage between 1945 and 1965 and the actions they took.
      Reasons nurses' wages remained low during this period of shortages and high
      demand were also examined to expand knowledge of nursing labor during a critical
      time in nursing history. METHOD: Historical analysis of primary and secondary
      sources generated between 1945 and 1965 including: (a) American Nurses'
      Association's (ANA) central files in Washington, DC; (b) ANA archives at the
      Mugar Memorial Library, Boston University; (c) official proceedings of the ANA's
      and American Hospital Association's (AHA) conventions; (d) nursing and hospital
      journals; (e) ANA and U.S. Government statistical documents and reports on the
      status of nursing labor; and (g) monographs on nursing, hospitals, the history of
      women's labor and the history of women in the 1940s, 1950s, and 1960s. FINDINGS:
      Hospital administrators and nurses disagreed on the causes of the nursing
      shortage and its remedies in the 20 years after World War II. Hospital managers
      believed the shortage occurred because many nurses left the work force to remain
      at home with their families. Nurses, however, identified low wages and deplorable
      working conditions as the cause. CONCLUSIONS: Hospital managers were successful
      at easing the shortage and controlling nursing costs by employing ancillary
      workers to replace RNs. Nurses took several different actions to deal with poor
      working conditions: initiating the ANA Economic Security Program, joining unions,
      and leaving hospital nursing.

PMID- 9775557
TI  - Understanding seasonal affective disorder and experiences in northern Norway.
AB  - PURPOSE: To better understand a diagnosis corresponding to mental distress and
      sleep disturbance associated with seasonal change known as seasonal affective
      disorder (SAD). DESIGN: This ethnographically guided investigation, conducted
      from 1993 through 1995 in Tromsoo, Norway at a latitude of 69 degrees north
      describes how the residents experience extreme seasonal change. METHOD:
      Qualitative interview data from 28 participants plus observation, folk wisdom,
      and literature were used to describe local understanding of seasonality and
      illustrate how cultural values, meanings, and practices can contribute to
      alternative experiences that differ from scientists' expectations. FINDINGS:
      While there is evidence that human physiologic alterations occur in response to
      the changing seasonal patterns of light and dark and to a greater extent, at
      latitudes further from the equator, the findings related to psychological changes
      and their causes remain inconsistent and controversial. CONCLUSION: Investigators
      concerned with the effects of seasonal change should be aware of and develop an
      appreciation of cultural perception and adaptation.

PMID- 9775558
TI  - Staying healthy in immigrant Pakistani families living in the United States.
AB  - PURPOSE: To determine the meaning of "staying healthy" as experienced by
      immigrant Pakistani families living in the United States. DESIGN:
      Phenomenological, interpretive using a convenience, purposive sample, in 1994, of
      members of four Pakistani immigrant families in one Midwestern U.S. city. METHOD:
      Heideggerian interpretive analysis applied to verbatim Urdu translated to English
      text by four researchers. FINDINGS: The relational themes found were: feeling
      understood, maintaining spiritual peace, keeping family and neighbor support,
      longing for the former way of being, and knowing how. Achieving wholeness was
      found to be the constitutive pattern. Participants viewed health as a dynamic
      experience of "being on the right path". CONCLUSIONS: Acceptance of care
      interventions depends on congruence with one's sense of what is "right"-
      spiritually as well as physically. Viewing health and illness as unitary and
      planning care once the meaning people assign to health and illness is clearly
      understood is important for clinical practice.

PMID- 9775559
TI  - Diabetes research in an American Indian community.
AB  - PURPOSE: To describe field experiences of a nurse-led team conducting
      collaborative research on diabetes with an American Indian community. Diabetes is
      of epidemic proportions among Indians. Methodological reports can assist nurse
      researchers to make important contributions to Indian health and diabetes care.
      ORGANIZING FRAMEWORK: Wax's stages of fieldwork: Initiation, fieldwork, post
      field work. SCOPE AND METHOD: Report of key research experiences from all phases
      of a study with an Indian community (1988-1996). Based on review of classic
      literature, field notes, and team meetings. FINDINGS: Methodological literature
      on research with Indians and cultural tutelage by Indians were helpful but
      neither sufficient nor infallible. A long period of investigator presence in the
      community before beginning the research was extremely useful. The need for
      researchers to explain their presence and the contribution of research to the
      community was ongoing. CONCLUSIONS: Wax's conception of field work as a dialectic
      process was supported. A collaborative, community focus and willingness to spend
      much time acquiring cultural knowledge can facilitate successful research on
      Indian health.

PMID- 9775560
TI  - World Wide Web search tools.
AB  - This article describes and compares five popular general search tools and two
      popular general metasearch tools. The tools and their related files in February
      1998 are the source of information and illustrations. A MEDLINE(R) search no
      longer guarantees retrieval of the most current, relevant, appropriate, and
      useful information. To meet demands for current information, the World Wide Web
      (WWW) must be searched. However, the enormous size of the WWW makes finding
      relevant information a difficult task. Fortunately, there are many automated
      search tools that can assist in locating relevant information quickly. Choosing
      the most appropriate tool depends on the type of information being sought.

PMID- 9775561
TI  - Shifting images of chronic illness.
AB  - PURPOSE: To describe results of a meta-study of client roles in two decades of
      qualitative research on elements of chronic illness experiences. While a vast
      body of qualitative health research has uncovered insider perspectives on a range
      of chronic diseases and their related illness experiences, systematic analysis
      has not been attempted, and research has not yet contributed to coherent
      theoretical developments. ORGANIZING CONSTRUCT: Health care relationships as
      articulated in the context of insider research into chronic illness experience.
      SOURCES: Elements of meta-theory, meta-method, and meta-data-analysis in the
      available qualitative research reports addressing chronic illness experience
      published 1980 through June 1996. Of over 400 published reports, 158 met the
      inclusion criteria and were subjected to systematic analysis on a number of
      themes, one of which is reported in this article. METHODS: Data selection,
      reduction, thematic analysis, and synthesis using constant comparative analysis.
      FINDINGS: Early conceptualizations of individuals with chronic illness shift from
      a focus on loss and burden toward images of health within illness,
      transformation, and normality. Parallel conceptualizations of health care
      relationships appropriate to chronic illness shift from client-as-patient to
      client-as-partner for the 15-year period. CONCLUSIONS: Meta-study permits
      critical analysis of the location of current inquiry into the larger context of
      systematic patterns in knowledge development. Researchers are cautioned against
      uncritical acceptance of current trends in interpretation.

PMID- 9775562
TI  - Middle-range theory of chronic sorrow.
AB  - PURPOSE: To introduce a middle-range nursing theory of chronic sorrow that
      presents this sorrow as a normal response to ongoing disparity due to loss.
      Chronic sorrow is the periodic recurrence of permanent, pervasive sadness or
      other grief related feelings associated with a significant loss. The theory
      provides a framework for understanding and working with people following a single
      or ongoing loss. ORGANIZING FRAMEWORK: The model of chronic sorrow includes
      antecedents, trigger events, and internal and external management methods. SCOPE:
      Theory is useful for analyzing individual responses of people experiencing
      ongoing disparity due to chronic illness, caregiving responsibilities, loss of
      the "perfect" child, or bereavement. SOURCES: The theory was developed using
      concept analysis, critical review of research, and validation in 10 qualitative
      studies of various loss situations. CONCLUSIONS: Chronic sorrow has been shown to
      explain the experience of people across the lifespan who encounter ongoing
      disparity because of significant loss. Nurses need to view chronic sorrow as a
      normal response to loss and, when it is triggered, provide support by fostering
      positive coping strategies and assuming roles that increase comfort.

PMID- 9775563
TI  - Research instrumentation and elderly subjects.
AB  - PURPOSE: To address instrumentation problems in conducting research with elderly
      subjects. SCOPE: The needs of older adults are considered with regard to
      instrument selection. Techniques for pretesting instruments are provided through
      illustrations from research reports and instrument development. Types of
      instruments are evaluated for use with older adults and methods for strengthening
      their applicability are provided. SIGNIFICANCE: Instrument development is sorely
      needed in gerontological research. Many of the instruments currently used to
      study elderly subjects lack adequate testing for applicability with old and very
      old populations. Knowledge about instrumentation can help researchers choose
      appropriate instruments for elderly subjects and strive to balance subject
      capacity and the demands of research. CONCLUSIONS: Four factors for consideration
      in selecting research instruments for use with older adults include subject (a)
      fatigue, (b) anxiety, (c) ethnic background, and (d) education. These factors are
      not adequately addressed in the current literature. Certain types of instruments
      may be more useful than others in studying the elderly.

PMID- 9775564
TI  - Vulnerability as a key to authenticity.
AB  - PURPOSE: Vulnerability is explored as a human trait that gives nurses an
      opportunity to engage in authentic nursing. Vulnerability in both nurse and
      patient is necessary for the practice of nursing with caring as its basic
      premise. ORGANIZING FRAMEWORK: Philosophic discourse. SCOPE: Vulnerability is
      explored in terms of its traditional connotation and existential meaning.
      CONCLUSIONS: To be authentic, nurses must be aware of their own vulnerability,
      recognize themselves in others, and be willing to enter into mutual
      vulnerability. If nurses deny the opportunity to be vulnerable, they deny the
      opportunity to participate in humanness and are more likely to dehumanize others.

PMID- 9775565
TI  - Tumour suppressor genes in lung cancer.

PMID- 9775567
TI  - Analysis of status of surgery in thoracic tuberculosis.
AB  - A retrospective analysis of the surgical procedure in 1655 patients in twenty
      years in a university hospital for thoracic tuberculosis revealed that the
      varieties of procedures were necessary in 2.2% cases only. They can be grouped as
      tubercular empyema with or without bronchopleural fistula in 1507 (91%),
      complicated pulmonary tuberculosis in 78 (4.7%), cold abscess in the chest wall
      with or without lymphadenitis in 54 (3.2%) and osteomyelitis of the ribs and
      sternum in 16 cases (0.9%). This is statistically significant with a confidence
      interval of 0.1248 to 0.2348. In tubercular empyema 222 procedures were performed
      of which 162 were minor procedures, intercostal drainage with irrigation: 89
      cases, thoracostoma: 56 cases and continuous chest wall tube 17 cases and 60 were
      major procedures (decortication in 45 cases, thoracoplasty [modified] in 14 cases
      and muscle transfer in one case). All the above procedures were preceded by an
      intercostal drainage. In complicated pulmonary tuberculosis the operative
      procedures were as follows: lobectomy in 33 cases, pneumonectomy in 35 cases and
      thoracoplasty in 10 cases. Drainage of cold abscess with or without lymphnode
      resection was performed in 54 cases and in 16 cases of osteomyelitis of the ribs
      and sternum resection were necessary. All procedures were performed under the
      cover of antitubercular therapy and supportive treatment with the aim of
      resolution of process, obliteration of the empyema space, control of sepsis and
      improvement of activity performance. The morbidity was extensive and mortality
      was high in major procedures. Good results could be obtained in over 92% cases,
      and only 66.2% on major surgery cases.

PMID- 9775566
TI  - Passive smoking, domestic fuels and lung function in north Indian children.
AB  - A study was carried out in 200 school children from north India to find out the
      effects of passive smoking and exposure to domestic cooking fuels on their lung
      functions. Forced vital capacity and FEV1 were the lowest in boys whose
      households used biomass fuel (p < 0.05) and PEFR and FEF 25% and 50% were lowest
      in boys with their homes using kerosene as fuels. All these were the best for LPG
      fuel. However, in girls there was no significant difference in different
      parameters, although the values were lower in those using kerosene and biomass
      fuel. All parameters were lower in passive smokers irrespective of the type of
      fuel used although they were not statistically significant. However, FEF 50% was
      significantly less in passive smokers whose households used mixed fuels. The same
      was true for PEFR, PEFR %, and FEF 25% in cases of LPG fuel use.

PMID- 9775568
TI  - Primary bronchogenic carcinoma: clinical profile of 279 cases from mid-west
      Rajasthan.
AB  - The present retrospective study was undertaken to study the clinical profile of
      primary bronchogenic carcinoma seen during last eight years in a teaching
      hospital. Out of a total of 279 diagnosed cases, 86% were males with an average
      age of 57 years, smoking was the risk factor in 81.6%. Forty percent of female
      patients were smoker with a significant overlap in use of smoking objects. Twenty
      four (8.8%) patients were less than 40 years of age at the time of diagnosis.
      Average duration of illness was 4.5 months. Weight loss (77%) and fever (34%)
      were the commonest general symptoms. Other chest symptoms include cough (68%),
      dyspnoea (59%), chest pain (22%), hemoptysis (20%) and dysphagia (6%). Fiberoptic
      bronchoscopy (FOB) (75%) and fine needle aspiration cytology (FNAC) (74.8%) were
      found to be the most efficient diagnostic procedures. Histologically, squamous
      cell carcinoma, adenocarcinoma, large cell carcinoma and small cell carcinoma
      were seen in 42%, 20%, 18% and 14% cases, respectively. Six percent patients
      showed malignant cells only and marked as unclassified. Radiologically,
      obstructive pneumonitis was the commonest presentation (59.5%) followed by mass
      lesion (31.8%) and rib destruction (5.1%). Inspite of its limitation, this study
      for the first time reports lung cancer pattern from mid-west Rajasthan.

PMID- 9775569
TI  - Patient education programme in bronchial asthma in India: why, how, what and
      where to communicate?
AB  - Judicious and prolonged use of 'protector' metered dose inhalers of steroid
      aerosol, sodium cromoglycate, both orally and nasally, and 'reliever' drugs like
      beta 2-agonists etc can induce a state of controlled asthma in many cases.
      Continued patient education programme (PEP) in a well-staffed asthma clinic is
      needed to achieve this state. Various aspects of PEP programme should be
      discussed during each visit. Presence of superstition, misconceptions, ignorance
      and strong bias against the use of metered-dose inhalers should be removed during
      PEP. Poor level of literacy, language-barrier, poverty and inadequate contingency
      fund for prolonged treatment in most families, poor medical infrastructure,
      inadequate health care facilities, overcrowding in all hospitals, insufficient
      para-medical staff-pattern (even in private hospitals), high cost of inhalers,
      tendency for early discontinuation of protector drugs, dislike for prolonged
      supervision and follow-up investigations, distrust for doctors, fear of social
      stigma, lure for homeopathy and indigenous branch of medicine for children, etc.,
      are some of the many problems, peculiar to our country, to be faced during PEP.
      Because of the presence of adequate medical and primary health care services, PEP
      in developed and affluent Western countries is liable to differ from what is
      advised here.

PMID- 9775571
TI  - Ectopic ascariasis: an unusual case of pyopneumothorax.
AB  - A patient of tuberculous pyopneumothroax with broncho-pleural fistula in whom a
      mature roundworm Ascaris lumbricoides migrated from the intestine to lodge itself
      in the pleural cavity is being reported.

PMID- 9775570
TI  - Cotrimoxazole induced toxic epidermal necrolysis in a suspected case of
      Pneumocystis carinii pneumonia with human immuno deficiency virus infection.
AB  - Toxic epidermal necrolysis due to trimethoprim sulphamethoxazole therapy in a
      subject of HIV with suspected pneumocystis carinii pneumonia, is reported,
      because of its rarity in Indian conditions. Patient showed excellent recovery on
      corticosteroid therapy.

PMID- 9775572
TI  - Two unusual cases of foreign body larynx.
AB  - Two adult patients of foreign body larynx who presented to us with a short
      history of foreign body inhalation with severe respiratory distress are being
      reported. They underwent elective tracheostomy preoperatively for maintenance of
      airway and the foreign body was removed successfully. We conclude that
      preoperative tracheostomy can be attempted to secure a patient's airway before
      resorting to removal of foreign body lodged in the larynx.

PMID- 9775573
TI  - An unusual presentation of pulmonary echinococcosis.
AB  - A case of pulmonary hydatid disease presenting with right supraclavicular cystic
      swelling is being reported. Radiologically, the cyst had an extension into the
      chest wall with bony involvement in the form of destruction and thinning of the
      first and second ribs on the right side. The patient responded to albendazole
      therapy.

PMID- 9775575
TI  - Rotavirus G and P types in children from Belem, northern Brazil, as determined by
      RT-PCR: occurrence of mixed P type infections.
AB  - Fifty-four group A rotavirus-positive stool samples, obtained from children aged
      less than three years during a longitudinal (December 1982 to March 1986) study
      in Belem, Brazil, were re-examined. The samples were tested by reverse
      transcription and polymerase chain reaction to determine their G-type and P-type
      specificity. Only 17 (32%) of these rotavirus strains could be successfully G-
      and P-genotyped. While 10 (59%) of the 17 strains showed single G- and P-type
      specificity, the remaining belonged to single G- and mixed P-genotypes. Rotavirus
      strains P[8], G1 and P[4], G1 predominated, accounting for 29% and 18% of the
      typed strains respectively. Mixed P-type infections caused by rotaviruses
      classified as P[8] + P[4], G1 were identified in 23% of cases. All but 3 of the
      54 rotavirus strains displayed long genomic profiles, as demonstrated by the
      analysis of RNA by polyacrylamide gel electrophoresis. Most (70%) rotavirus
      strains with single G- and P-type specificity were detected during the first year
      of life, whereas 5 (71%) of the seven mixed P-type infections occurred throughout
      the second or third year of age. Reinfections were noted in two children, both of
      them being infected with P[8] + P[4], G1 rotavirus strains when aged 20 months.
      The high proportion of untypeable rotavirus strains suggests that unusual types
      may be circulating in Belem. In addition, the occurrence of mixed P-type
      infections in our region indicates the potential for reassortment between
      different rotavirus genogroups. Monitoring of these rotavirus strains may have
      important implication in the context of future strategies of rotavirus
      vaccination in Brazil.

PMID- 9775574
TI  - Intestinal amoebiasis: antibody-secreting cells and humoral antibodies.
AB  - Splenic plasma cell response and systemic antibody response to intestinal
      amoebiasis were studied in C3H/HeJ mice from 5 to 60 days post-inoculation with
      Entamoeba histolytica. At various time intervals specific antibody-secreting
      cells (ASC) in the spleen were measured in infected mice and non-infected control
      mice by enzyme-linked immunospot (ELISPOT) assay. Serum antibodies were measured
      by enzyme-linked immunosorbent assay (ELISA). The infected animals showed high
      IgA ASC from 30 to 50 days post-inoculation as compared to IgM and IgG ASC.
      However, class-specific serum antibody showed high IgG titre from 30 to 60 days
      post-inoculation as compared to IgM and IgA serum titres. Our results suggest
      that E. histolytica trophozoites can induce a plasma cell response in the spleen
      that is different from anti-amoebic antibody response in serum.

PMID- 9775576
TI  - A simple method for measuring caeco-colonic transit time in mice.

PMID- 9775578
TI  - The changing role of receiving hospitals under the Emergency Medical Treatment
      and Active Labor Act.

PMID- 9775577
TI  - De facto health-care rationing by age. The law has no remedy.

PMID- 9775579
TI  - The emerging convergence of the doctrine of informed consent and judicial
      reinterpretation of the Employee Retirement Income Security Act.

PMID- 9775580
TI  - Understanding and applying alternative dispute resolution methods in modern
      medical conflicts.

PMID- 9775581
TI  - Is utilization review the practice of medicine? Implications for managed care
      administrators.

PMID- 9775582
TI  - Establishment of the tortoise tick Amblyomma marmoreum (Acari: Ixodidae) on a
      reptile-breeding facility in Florida.
AB  - The tortoise tick Amblyomma marmoreum Koch was found to be established on a
      reptile facility in central Florida. Over a 5-mo period, 443 ticks were collected
      from tortoises, dogs, and vegetation. Collections from hosts were primarily from
      3 species of exotic tortoises, including leopard tortoises, Aldabra tortoises,
      and yellow-footed tortoises. The total numbers of ticks present, the presence of
      all life stages, and the slow development of this species indicate that this is
      not a recent infestation. The source of the infestation is unknown because no
      tortoises were imported or moved onto this premise within the previous year. The
      propensity of this tick to feed on mammals and reptiles as immatures, its status
      as an experimental heartwater vector, and potential for further accidental
      introductions to the United States elicit concern toward the more widespread
      establishment of this species.

PMID- 9775583
TI  - Experimental infection of domestic cats with Bartonella henselae by inoculation
      of Ctenocephalides felis (Siphonaptera: Pulicidae) feces.
AB  - Caged cat fleas, Ctenocephalides felis (Bouche), were fed on 6 cats; 3 cats were
      injected with 5 x 10(7) colony forming units of Bartonella henselae intradermally
      and 3 cats were injected with an equal volume of saline. After the fleas fed for
      4 d, 5 groups of 50 B. henselae-exposed fleas were caged and allowed to feed on 5
      cats for 6 d. Five cats each were injected intradermally with 1 ml of saline
      containing 45 mg of feces from B. henselae-exposed fleas. Five cats were fed 50
      B. henselae-exposed fleas and 45 mg of fresh feces from B. henselae-exposed
      fleas. Five cats received all 3 treatments by using fleas and feces collected
      from cats inoculated with saline (controls). Cats were bled weekly and tested by
      culture and serology. The cats that were injected with feces from infected fleas
      were positive by culture for B. henselae at 1 or 2 wk after exposure and were the
      only cats to become bacteremic or seropositive by week 20.

PMID- 9775584
TI  - Reported distribution of Ixodes scapularis and Ixodes pacificus (Acari: Ixodidae)
      in the United States.
AB  - Lyme disease, caused by infection with Borrelia burgdorferi, is the most
      frequently reported arthropod-borne disease in the United States. To develop a
      national map of the distribution of the vectors of B. burgdorferi to humans
      (Ixodes scapularis Say and Ixodes pacificus Cooley & Kohls ticks), we sent
      questionnaires to acarologists, health officials, and Lyme disease researchers;
      surveyed the 1966-1996 MEDLINE data base; and reviewed 1907-1995 National Tick
      Collection data. Tick collection methods cited included flagging and dragging,
      deer surveys, small- and medium-sized mammal surveys, CO2 baiting, and receipt of
      tick submissions. A total of 1,058 unique, county-specific I. scapularis and I.
      pacificus records was obtained. Tick populations were classified as "reported" (<
      6 ticks and 1 life stage identified) or "established" (> or = 6 ticks or > 1 life
      stage identified). Established populations of I. scapularis were identified in
      396 counties in 32 states in the eastern and central United States, whereas
      established populations of I. pacificus were found in 90 counties in 5 western
      states. Counties with established populations were most concentrated in the
      northeastern, upper northcentral, and west-coastal states but were also clustered
      in southeastern and Gulf-coastal states. A less concentrated distribution was
      found in the south-central states. Reports were notably missing from all but a
      few counties in Ohio, West Virginia, western Virginia and North Carolina,
      Kentucky, and Tennessee. They were absent in the Great Plains and Rocky Mountain
      regions and from large areas of western states east of the Cascade and Sierra
      Nevada cordilleras. These data are useful for identifying areas of Lyme disease
      risk, for targeting Lyme disease prevention strategies, and for monitoring trends
      in spatial distribution of Lyme disease vector ticks.

PMID- 9775585
TI  - Effect of body size on host seeking and blood meal utilization in Anopheles
      gambiae sensu stricto (Diptera: Culicidae): the disadvantage of being small.
AB  - The survival, metabolic reserves, and host-seeking response of unfed Anopheles
      gambiae Giles sensu stricto females of different size classes were investigated
      from 1 to 6 d after emergence. In addition, the effect of blood meal size and
      frequency of feeding on the accumulation of metabolic reserves and reproductive
      development were investigated during the 1st gonotrophic cycle. Large females
      survived longer and contained significantly more protein, glycogen, and lipid at
      emergence than did small females. Over 6 d, the host-seeking response of large
      mosquitoes was greater than that of small ones. There was no gonotrophic
      development in unfed small females after emergence, whereas < or = 52% of large
      females developed oocytes to Christophers stage II. One blood meal, given by
      enema, resulted in gonotrophic development to stage II in small females, whereas
      only large females matured oocytes to Christophers stage V. In both large and
      small females, egg development was related to the size of the blood meal, but
      large females were better able to utilize the meals. Two successive blood meals
      enhanced the ability of small females to develop eggs. The pregravid condition
      commonly observed in An. gambiae appears to be determined by insufficient
      metabolic reserves at emergence, and the probability for small individuals to be
      pregravid is greater than for large mosquitoes because of the need to build up
      sufficient energy reserves before gonotrophic development can occur. The
      consequence of this behavior in relation to malaria transmission is discussed.

PMID- 9775586
TI  - New procedures to estimate water temperatures and water depths for application in
      climate-dengue modeling.
AB  - Two new approaches have been developed to estimate water temperatures and water
      depths in containers that commonly are used as breeding sites for mosquitoes, the
      primary vectors of dengue viruses. These estimates are incorporated in recently
      developed stochastic simulation models used to describe the daily dynamics of
      dengue virus transmission in the urban environment. Water temperature estimates
      are provided through a regression model that includes meteorological variables
      not previously used; results show that they are significantly better than those
      used in previous dengue transmission models. Water depth models use a climatic
      water budget approach which estimates moisture storage within containers. The
      water depth models are less precise than those developed for water temperature;
      however, results are superior to those used in previous models. These new
      approaches should improve estimates of the impact of water conditions on dengue
      vectors.

PMID- 9775587
TI  - Minimum infection rate of Ambylomma americanum (Acari: Ixodidae) by Ehrlichia
      chaffeensis (Rickettsiales: Ehrlichieae) in southern Indiana.
AB  - In 1994 and 1995, 8 cases of human monocytic ehrlichiosis were confirmed. These
      cases originated from southern counties where the putative tick vector Ambylomma
      americanum (L.) is well established. To confirm the presence of Ehrlichia
      chaffeensis in ticks in southern Indiana and to determine the minimum infection
      rate, specimens of A. americanum were collected from 5 counties (7 sites).
      Nucleic acid was isolated from 88 pools of ticks (430 individuals) using an
      optimized phenol/CTAB (cetyltrimethylammonium bromide) extraction procedure and
      subjected to polymerase chain reaction analysis using species-specific 16S rRNA
      gene bacterial primers. Twenty-one of 88 pools (a minimum of 21 of 430
      individuals) were positive for the presence of E. Chaffeensis, yielding an
      average minimum infection rate of 4.9%. Minimum infection rates at individual
      sites ranged from 0 to 9.4%. These data extend the known distribution of the
      bacterium to 3 southern counties of Indiana and suggest a higher prevalence of E.
      chaffeensis than previously reported for Missouri, North Carolina, or Kentucky.

PMID- 9775588
TI  - Role of Anopheles quadrimaculatus and Coquillettidia perturbans (Diptera:
      Culicidae) in the transmission cycle of Cache Valley virus (Bunyaviridae:
      Bunyavirus) in the midwest, USA.
AB  - Midwestern populations of Coquillettidia perturbans (Walker) and Anopheles
      quadrimaculatus (Say) were tested for their ability to transmit Cache Valley
      virus (CV), a recognized human and animal pathogen. Field-collected mosquitoes
      were fed artificial blood meals containing 5.2-6.2 log10 pfu/ml of CV. After 9-23
      d at 28 degrees C, 75-93% of blood-fed Cq. perturbans had disseminated infections
      and 6-62% transmitted the virus to suckling mice. However, when infected with a
      lower virus titer (3.3 log10 pfu/ml), only 10-36% of the mosquitoes had
      disseminated infections and 0-10% transmitted the virus to suckling mice. A
      similar infection rate (21%) was observed in Cq. perturbans fed on viremic (3.2
      log10 pfu/ml) hamsters. An. quadrimaculatus were infected (81-100%) by both doses
      used, with transmission rates ranging from 13-67% after 16-23 d of incubation.
      Transmission rates for the laboratory strain An. quadrimaculatus SAVANNAH ranged
      from 20 to 33% after 7-14 d of incubation. Our data show that although An.
      quadrimaculatus is more susceptible to CV infections than Cq. perturbans, both
      mosquito species could be involved in the midwestern transmission cycle of the
      virus.

PMID- 9775589
TI  - Overcrowding of Culex sitiens (Diptera: Culicidae) larvae: population regulation
      by chemical factors or mechanical interference.
AB  - Crowding of Culex sitiens Wiedemann larvae was investigated to determine whether
      pupation was delayed by the presence of chemical factors in the water or by
      mechanical interference. As the larval density increased from 0.05 to 1.0 larvae
      per milliliter of water, the duration of larval development increased from 7.5 to
      23.0 d and larvae mortality increased from 1.7 to 99.6%. At high larval densities
      (2 larvae per milliliter), the larvae did not pupate, but remained alive as 4th
      instars for at least 50 d, even after their abundance subsequently declined due
      to mortality. When not crowded, 80% of the larvae fed at the surface; the
      remainder fed mainly on the bottom (even at a depth of 35 cm). Removal of
      chemical retardants by changing the water daily increased pupation to 65%
      (compared with 4% in controls, in which the water was not changed), but this was
      less than the effect of reducing mechanical interference by increasing the
      surface area, which increased pupation to 98%. Therefore, the main density
      dependent factor was mechanical interference during feeding, but prolonged
      development to 19 d showed that chemical retardants also were important. The
      chemical retardant was not stable, so that 2nd generation larvae reared in the
      same water were unaffected, but its effect was irreversible, because most crowded
      larvae moved to clean water and a lower density did not pupate.

PMID- 9775590
TI  - Effect of salt concentration in larval rearing water on susceptibility of Aedes
      Mosquitoes (Diptera: Culicidae) to eastern equine and Venezuelan equine
      encephalitis viruses.
AB  - The effect of salt concentration in larval rearing water on the susceptibility of
      adult Aedes taeniorhynchus (Wiedemann) and Aedes sollicitans (Skuse) to infection
      with eastern equine encephalomyelitis (EEE) virus was tested in the laboratory.
      Ae. sollicitans was more susceptible to infection (79%, n = 82) and viral
      dissemination (16%) with EEE virus than was Ae. taeniorhynchus (42%, n = 184) and
      (5%), respectively, when fed on a chick with a viremia of 10(7) +/- 0.1 plaque
      forming units/ml; however, infection rates in adults were not affected by rearing
      in salt concentrations ranging from fresh water to brackish water containing 2.4%
      sea salts (1 part fresh water and 2 parts seawater). When fed on the same viremic
      6-d-old chicken, all 48 Aedes albopictus (Skuse), reared in fresh water, became
      infected. Similarly, Venezuelan equine encephalitis viral infection or
      dissemination rates did not vary among Ae. taeniorhynchus adults that were reared
      in water containing 0, 1, or 2% sea salts.

PMID- 9775591
TI  - Development of Alouattamyia baeri (Diptera: Oestridae) from howler monkeys
      (Primates: Cebidae) on Barro Colorado Island, Panama.
AB  - The fecundity and development of larval stages of the cuterebrid bot fly A. baeri
      were studied in an unusual host, remotely related to the primary host. Third
      instar Alouattamyia baeri (Shannon & Greene) removed from howler monkeys,
      Alouatta palliata, were allowed to pupate and then were cultured under controlled
      conditions. Eclosion occurred after 37.9 +/- 0.4 (mean +/- SE) (male) and 38.2 +/
      0.4 (female) d at 26 degrees C. Five-day-old females were mated using a tethered
      flight technique and oviposited on ridged filter paper. The total egg complement
      was 1,399 +/- 243 (n = 2) eggs per female. Eggs were fully embryonated after
      incubation for 5 d at 26 degrees C. Eggs hatched when warmed in the palm of the
      hand. Hatching of eggs from an individual batch was asynchronous. Newly hatched
      larvae would not penetrate intact skin on a rabbit, Oryctolagus cuniculus L.
      Larvae placed near the nares or on the ocular conjunctiva migrated rapidly from
      view. Warbles containing larvae were first observed on infested rabbits 5 d after
      infestation. Development of larvae proceeded until day 39 after infestation, when
      nearly mature 3rd instars were observed. None of the larvae survived to pupate.

PMID- 9775592
TI  - Measurement of flight tone differentiates among members of the Anopheles gambiae
      species complex (Diptera: Culicidae).
AB  - Through digital sampling and resampling at 5,000 and 20,000 Hz of amplified
      mosquito flight sound, baseline separation was observed for flight tone frequency
      distributions of male and female Anopheles gambiae Giles, An. arabiensis Patton,
      An. merus Donitz, and An. melas Theobald. Males of the 4 species showed flight
      tones considerably higher than females. Up to 7 harmonics were measured for each
      species. Close correspondence for each individual mosquito of the means of the
      flight tone harmonics (corrected for harmonic number) demonstrated the accuracy
      and precision of the method. These data indicate that flight tone differences
      have been subjected to selection and may act as an isolating mechanism for mating
      or serve some other behavioral purpose in these mosquitoes. Individuals and
      swarms of sympatric species were distinguished from each other for both males and
      females, but the allopatric species, An. merus and An. melas, were
      indistinguishable.

PMID- 9775593
TI  - Honeydew sugars in wild-caught female deer flies (Diptera: Tabanidae).
AB  - Female deer flies (Chrysops spp.) were collected from 2 habitats in Algonquin
      Provincial Park, ON. Using thin-layer chromatography, 11 sugars were detected in
      the digestive tracts of these flies; these occurred in 41 different combinations.
      We argue that combinations including melezitose, stachyose, or both can be used
      to indicate when flies recently have fed on homopteran honeydew. Accordingly,
      85.7% of Chrysops excitans (n = 49) and 61.1% of Chrysops mitis (n = 18)
      collected from an abandoned airfield and 69.8% of C. excitans (n = 53) and 60.0%
      of C. mitis (n = 15) from a bog habitat tested positive for these honeydew
      indicator sugars. The difference between species was significant at the airfield
      only. Possible reasons for this habitat-dependent difference are discussed.

PMID- 9775595
TI  - Effects of temperature on Sarcophaga haemorrhoidalis (Diptera: Sarcophagidae)
      development.
AB  - Growth curves were studied for the larva and pupa of Sarcophaga haemorrhoidalis
      (Fallen) under cyclic temperatures with means of 15.6, 21.1, 26.7, and 35 degrees
      C, and a constant temperature of 25 degrees C. Development from 1st instar to
      adult under all regimes ranged from 252 to 802 h. A constant temperature of 25
      degrees C produced a range of pupation times from 93 to 153 h, with adult
      emergence ranging from 252 to 502 h. A maximal preferential temperature of 30
      degrees C was determined for maggots by using a gradient system. This study shows
      that S. haemorrhoidalis can be used as an indicator species when establishing a
      postmortem interval as long as the investigator accounts for the developmental
      variation prevalent within this species.

PMID- 9775594
TI  - Laboratory and field evaluation of the repellents deet, CIC-4, and AI3-37220
      against Anopheles farauti (Diptera: Culicidae) in Australia.
AB  - Laboratory and field tests of the repellents diethyl methylbenzamide (deet), 1-(3
      cyclohexen-1-yl-carbonyl)-2-methylpiperidine (AI3-37220), and (2
      hydroxymethylcyclohexyl) acetic acid lactone (CIC-4) were conducted against
      Anopheles farauti s.s. Laveran, an important malaria vector in the southwest
      Pacific region. In the laboratory, An. farauti was tolerant of all 3 repellents,
      but deet and CIC-4 provided significantly better protection than AI3-37220. The
      field study was conducted in rain forest located near Innisfail, northern
      Queensland, and tested 25% (vol:vol) ethanol solutions of each repellent against
      An. farauti. All 3 repellents provided > 95% protection against An. farauti for 5
      h after application. In contrast to the laboratory tests, protection provided by
      AI3-37220 was significantly better than that by either deet or CIC-4, and there
      was no difference between protection by deet and CIC-4. The protection by deet
      and CIC-4 declined 8 h after application and provided < or = 50% protection at 9
      h. In contrast, AI3-37220 provided > or = 94% protection for 9 h.

PMID- 9775596
TI  - Field evaluation of Mesocyclops longisetus (Copepoda: Cyclopoidea) for the
      control of larval Aedes aegypti (Diptera Culicidae) in northeastern Mexico.
AB  - Field trials of the predacious copepod Mesocyclops longisetus Thiubaud were
      conducted in northeastern Mexico to determine the effectiveness of this species
      to control larval Aedes aegypti (L.) populations and to survive and reproduce in
      nature. Groups of 200, 50, and 50 ovigerous M. longisetus females were inoculated
      into 200-liter metal drums, discarded tires, and cemetery flower vases,
      respectively, which are 3 of the more important Aedes breeding sites in this
      area. Larvae were sampled at 15-d intervals, and total surviving cyclops were
      collected at the end of the study, 120 d later. Community participation was
      solicited through a simple training program on copepod rescue before drum
      cleaning and facilitated by the addition of a drum marker to remind residents of
      copepod presence. Results showed good cooperation and after 4 mo all peridomestic
      drums, still supported variable numbers of cyclopoids. Average of larvae
      reduction was 37.5% for drums, 67.5% for flower vases, and 40.9% for tires. This
      study shows difficulties of using cyclopoids for tires and vases in areas where
      prolonged dry seasons desiccated these habitats and reduced copepod survival.

PMID- 9775597
TI  - Seasonal colonization and decomposition of rat carrion in water and on land in an
      open field in South Carolina.
AB  - Decomposition and insect colonization of rat, Rattus rattus L., carrion on land
      and in water were compared during summer and winter in a plowed field in
      northwestern South Carolina. During winter, carcasses on land reached the dried
      remains stage of decomposition, whereas carcasses in water reached the early
      floating stage. During summer, carcasses in both habitats entered the final
      remains stage of decomposition in 1-2 wk. Fewer than 30 species of carrion
      insects were recorded from the carcasses over the duration of the study, probably
      reflecting the small size of the carcasses and the depauperate fauna of the
      habitat. Three species of blow flies--Cynomyopsis cadaverina (Robineau-Desvoidy),
      Calliphora vicina Robineau-Desvoidy, and Lucilia illustris (Meigen)--colonized
      carrion on land during winter, but no insects colonized carrion in water during
      winter. Two species of blow flies, Cochliomyia macellaria (F.) and Phaenicia
      sericata (Meigen), and 1 species of flesh fly, Sarcophaga bullata Parker,
      colonized the carrion on land and in water during summer; the blow fly, Phormia
      regina (Meigen), colonized only the carrion on land. This study demonstrated
      seasonal variation in decomposition and colonization patterns of carrion in
      contrasting habitats, with important implications for forensic entomology.

PMID- 9775598
TI  - Screening of Haematobia irritans irritans (Diptera: Muscidae) populations for
      pyrethroid resistance-associated sodium channel gene mutations by using a
      polymerase chain reaction assay.
AB  - A polymerase chain reaction (PCR)-based rapid screening procedure was developed
      to test individual horn flies, Haematobia irritans irritans (L.), for the
      presence of a specific nucleotide substitution in the sodium channel gene
      sequence that has been associated with pyrethroid resistance. By a systematic
      optimization of reaction conditions and judicious choice of PCR primers differing
      in DNA sequence by a single nucleotide, we identified pyrethroid-susceptible or
      resistant sodium channel alleles in individual flies. Laboratory and field
      populations were examined by both the PCR assay and conventional filter paper
      bioassays with the pyrethroid cyhalothrin to verify that populations containing
      greater proportions of individuals with the resistant sodium channel allele DNA
      sequence also had higher bioassay LC50 values. The PCR assay for resistance
      alleles gave definitive information on the genotype of an individual fly and
      detected the presence of heterozygous individuals that might serve as reservoirs
      of resistance genes in field populations.

PMID- 9775599
TI  - Relative fitness of three organophosphate-resistant strains of Culex pipiens
      pallens (Diptera: Culicidae).
AB  - Effects of dipterex, temephos, and chlorpyrifos resistance on the relative
      fitness of Culex pipiens pallens (L.) were evaluated by examining developmental
      and reproductive characteristics. Age-specific life tables of Dip-R- (dipterex),
      Tmo-R- (temephos), and Chl-R- (chlorpyrifos) resistant strains were compared with
      the susceptible strain to determine relative fitness based on population trend
      indices (I). The 3 organophosphate-resistant strains possessed reproductive and
      developmental disadvantages involving fecundity and survival relative compared
      with the susceptible strain, with relative fitness values of 0.465, 0.520, and
      0.501, respectively. These results are discussed in relation to the reversal from
      resistance to susceptibility in natural populations of mosquitoes.

PMID- 9775600
TI  - Mode of action of lufenuron on larval cat fleas (Siphonaptera: Pulicidae).
AB  - Adult cat fleas, Ctenocephalides felis (Bouche), were fed suboptimal in vitro
      concentrations of lufenuron in blood to allow hatching of flea larvae for
      cytological study. At concentrations of 0.125, 0.25, and 0.5 ppm, larval hatch
      was 64, 15, and 4%, respectively. Larvae hatching from eggs laid by adults fed
      lufenuron at concentrations of 0.025, 0.08, or 0.125 ppm did not differ
      significantly from the control. However, many larvae from the 0.08-ppm group and
      higher concentrations died during the 1st instar. Examination of these larvae
      revealed that they were dying from desiccation caused by bleeding from
      microscopic lesions in the cuticle or the inability to complete the molt to the
      next instar. Electron micrographs showed that lufenuron often disrupted formation
      of the endocuticle resulting in the deposition of an amorphous mass of randomly
      oriented chitin microfibrils. Other larvae formed normal endocuticle but were
      unable to digest the old endocuticle or produce new procuticle after apolysis.
      Failure of larvae to digest old cuticle or form new cuticle was caused by
      degeneration of the epidermal cells needed for the synthesis of molting fluid and
      chitin.

PMID- 9775601
TI  - Effects of cold stress on survival and reproduction of Haematobia irritans
      (Diptera: Muscidae).
AB  - Adult horn fly, Haematobia irritans (L.), survival, mating success, and ovarian
      development were measured following exposure of pupae to 4 degrees C for 2, 3,
      and 4 wk, and were compared with an untreated control group held at 29 degrees C.
      Survival varied inversely with duration of low-temperature exposure, and ranged
      from 92.1% in the control to 7.0% following a 4-wk exposure. Mating success also
      varied inversely with duration of low-temperature exposure, and ovarian
      development was delayed, especially in the week 4 group. Reproductive and
      population parameters were measured in a 2nd cohort of horn flies following
      exposure of pupae to 1-4 wk at 4 degrees C, and in a control. Adult longevity
      varied inversely with duration of exposure. Mean longevity was greatest in the
      week 1 group at 17.6 d, followed by the control at 14.7 d. Week 4 flies lived an
      average of 2.2 d and produced no eggs. The preoviposition period was longest in
      the week 3 group at 7.3 d. In cohort 2, control and week 1 flies produced the
      highest number of eggs, eggs per female, and eggs per day compared with other
      groups. Eggs were produced over a mean of 6.8 d by week 3 flies compared with
      25.4 d by week 1 flies. Reproductive rates varied inversely with low-temperature
      exposure duration, as did F1 generation egg hatch, larval development, and adult
      emergence. Survivorship and fecundity schedules are discussed with respect to the
      effects of low-temperature exposure duration. The effects of low-temperature
      exposure duration on horn fly reproduction and life-history patterns are
      discussed with respect to rearing, storage, and ecology.

PMID- 9775602
TI  - Taxonomic review of Cotingacola (Phthiraptera: Philopteridae) from the cotingas
      (Passeriformes: Tyrannidae), with descriptions of two new species.
AB  - The genus Cotingacola currently contains 14 species and subspecies described by
      Carriker. A careful examination of these reveals only 6 valid taxa with 8 names
      placed as junior synonyms. These new synonymies are Cotingacola rupicolae
      colombiana, C. latigastra, C. temporalis and C. longicrucis, synonyms of C.
      rupicolae; C. foramina, C. graciligastra and C. tityra, synonyms of C. tergalis;
      C. acuticeps, a synonym of C. dimorpha. Two new species are described from
      Peruvian material: C. stotzi (type host: Querula purpurata) and C. fitzpatricki
      (type host: Lipaugus subalaris). A key is provided for identification of the 8
      species.

PMID- 9775603
TI  - Population parameters of Triatoma spinolai (Heteroptera: Reduviidae) under
      different environmental conditions and densities.
AB  - Population parameters of Triatoma spinolai Porter were studied using specimens
      collected in the north and central region of Chile. Two cohorts of 17 and 44
      first instars were maintained at a constant temperature of 28 degrees C and 70%
      RH. Two similar cohorts of bugs were exposed to 16-24 degrees C and 55-75% RH and
      maintained under a photoperiod of 14:10 (L:D) h for 16 mo. The preimaginal period
      ranged between 285 and 372 d under constant conditions. The lower-density cohort
      required 9.5 mo to reach the adult stage compared with 12.4 mo for the high
      density cohort. Bugs placed under variable temperature and relative humidity
      conditions did not survive long. Cohorts with higher densities had similar
      mortality rates with greater mortality occurring in cohorts that had lower
      numbers of bugs. Cohorts under constant temperature and relative humidity
      reproduced and basic reproduction rates (Ro, intrinsic growth rate [r], and
      generation time [G]) were estimated. Cohorts with higher numbers of bugs had
      higher Ro and r, whereas values of G were similar for both groups. Apparently, 25
      degrees C was a critical temperature threshold for T. spinolai and there appeared
      to be a minimal population density that allowed reproduction.

PMID- 9775604
TI  - Determination of sample sizes for the estimation of Onchocerca volvulus
      (Filarioidea: Onchocercidae) infection rates in biting populations of Simulium
      ochraceum s.l. (Diptera: Simuliidae) and its application to ivermectin control
      programs.
AB  - Monthly samples of biting Simulium ochraceum s.l. Walker were collected before
      and after ivermectin treatment in southern Mexico and analyzed for Onchocerca
      volvulus Leuckart infection rates, infection intensity, and the characteristics
      of larval distribution among parous flies. The variance over mean ratio (VMR)
      indicated that in all cases this distribution departed from Poisson and was
      strongly aggregated (VMR > 1). The negative binomial was found to be an adequate
      model with a small value of the aggregation parameter k, but the degree of larval
      overdispersion increased as the mean larval load decreased, invalidating the use
      of a common kc value. A linear relationship between k and the mean (mu) was
      established, k(mu) = k1 mu, which permitted exploration of the relationship
      between the observed proportion of infected flies, p, and the estimated mean
      larval burden per fly, m (all larval stages in parous flies). This would allow
      mean numbers of larvae per parous fly to be predicted from presence-absence data
      (e.g., from infection rates provided by polymerase chain reaction methods applied
      to pools of flies), assuming that k1 is a known parameter. Given that both p and
      m are naturally low in S. ochraceum, their relationship was practically linear
      within the range of observed values. Predictions were tested with the Mexican
      data from which the clumping parameter was estimated as well as for Guatemalan
      data for which this information was not available. Results showed a highly
      satisfactory degree of agreement between predictions and observations. The sample
      sizes required to estimate mean larval loads from prevalence data for fixed
      levels of precision (defined as the ratio between SE[m] and m) were calculated
      for realistic S. ochraceum infection rates (those found in published pre- and
      postcontrol field surveys as well as in this work). For the special case in which
      the relationship between k and the mean is linear and goes through the origin,
      k(mu) = k1 mu, the number of flies to be examined for O. volvulus infections does
      not explicitly depend on the aggregation parameter, but rather on the unknown
      proportion of infected flies. Practical recommendations for the calculation of
      sample sizes are discussed. For infection levels < 0.2%, a minimum number between
      6,000 and 13,000 parous flies would have to be examined to estimate the mean
      larval load with a precision between 0.20 and 0.30. The linearity between
      onchocercal infection rate and infection intensity in the fly population
      indicates that relationships between the former and onchocerciasis patterns in
      the human population should be further explored for the purposes of monitoring
      the impact of ivermectin control programs through entomological evaluations.

PMID- 9775605
TI  - Surveillance for arthropod-borne viral activity in Nebraska, 1994-1995.
AB  - A 2-yr arbovirus surveillance program was established in Nebraska following the
      midwest flood of 1993. CDC light traps were used to collect mosquitoes at 11
      localities throughout Nebraska. In 1994, we collected 685,582 mosquitoes, and we
      tested 1,359 pools of Culex mosquitoes for arbovirus infection, with St. Louis
      encephalitis virus isolated from 2 pools collected in Scotts Bluff County in
      western Nebraska. In 1995, 1,163,741 mosquitoes were collected and 2,788 pools
      tested, with 36 positive for western equine encephalomyelitis (WEE) virus. Thirty
      of the WEE-positive pools were collected in Scotts Bluff County, 4 pools from the
      city of Norfolk and 2 from the city of Grand Island. All viruses were isolated
      from Culex tarsalis Coquillett. The highest minimum infection rate of 3.81 per
      1,000 mosquitoes was observed in Scotts Bluff County on 13 September 1995. The
      seasonal minimum infection rate for WEE was 0.52 in Scotts Bluff County. No human
      or horse disease attributed to arboviral infection was reported in Nebraska
      during 1994 and 1995.

PMID- 9775606
TI  - Seasonal changes in abundance and gonotrophic age of host-seeking Tabanidae
      (Diptera) from a subarctic Labrador peatland.
AB  - Canopy and Malaise traps continuously sampled host-seeking female tabanids
      throughout the 1990 and 1991 flight seasons at Iron Arm Fen in subarctic
      Labrador. A total of 19,426 tabanids representing 3 genera and 18 species was
      collected. Subsamples of each daily catch were dissected to determine gonotrophic
      age. Horse flies (mainly Hybomitra spp.) accounted for 96% of all tabanids; the
      remainder were deer flies (Chrysops spp.). Hybomitra arpadi (Szilady) and
      Hybomitra aequetincta (Becker) were the dominant species, comprising 60.6 and
      24.8% of collections, respectively. They were also among the 1st species to
      emerge (in early July) and persisted for the entire flight season (until mid
      August). Seasonal abundance for each species varied between the 2 yr of study.
      Both H. arpadi and H. aequetincta were obligately anautogenous at Iron Arm Fen.
      Seasonal changes in the gonotrophic age structure of host-seeking females of
      these species indicated a mid-July emergence peak in 1990 and an early July peak
      in 1991. Among the other tabanid species collected at Iron Arm Fen, Hybomitra
      lurida (Fallen) and Hybomitra zonalis (Kirby) were facultatively autogenous,
      whereas Hybomitra pechumani (Teskey & Thomas), Hybomitra hearlei (Philip),
      Hybomitra frontalis (Walker), Hybomitra astuta (Osten Sacken), Chrysops zinzalus
      (Philip), and Chrysops nigripes Zetterstedt were obligately autogenous during
      their 1st ovarian cycle.

PMID- 9775607
TI  - Sequence heterogeneity in copia-like retrotransposons in Anopheles (Diptera:
      Culicidae) in Thailand.
AB  - Degenerate primers and the polymerase chain reaction (PCR) detected a conserved
      region of copia-like reverse transcriptase from Anopheles mosquitoes in Thailand.
      A total of 43 subclone PCR fragments of the size expected for reverse
      transcriptase of copia-like elements was isolated from Anopheles dirus (Peyton &
      Harrison) subspecies A, Anopheles maculatus (Theobald) subspecies E, Anopheles
      nivipes (Theobald), and Anopheles subpictus Grassi. Sequence analysis of
      subclones confirmed the identity of these sequences as copia-like reverse
      transcriptase sequences. The sequences displayed varying degrees of sequence
      heterogeneity, in contrast to the limited diversity seen in copia-like elements
      in Drosophila. Phylogenetic analysis of the amino acid sequences of the subclones
      showed that the majority of the retroelements were clustered together, implying
      that sequence divergence during vertical transmission of the copia-like
      retrotransposons has been a major factor in the evolution of copia-like
      retroelements in Anopheles species. Additionally, there is evidence that
      horizontal transfer of this transposon group among certain divergent taxa also
      may have played a role in their evolution.

PMID- 9775608
TI  - Cuticular hydrocarbon composition analysis for taxonomic differentiation of
      phlebotomine sandfly species (Diptera: Psychodidae) in Kenya.
AB  - Gas chromatographic patterns of cuticular hydrocarbon composition were analyzed
      for 9 sandfly species, including Phlebotomus (Larroussius) aculeatus Lewis,
      Minter & Ashford [syn. P. (L.) elgonensis Ngoka, Madel & Mutinga], P. (sensu
      stricto) duboscqi Neveu-Lemaire, P. (Synphlebotomus) martini Parrot, P. pedifer
      (Larroussius) Lewis, Mutinga & Ashford, Sergentomiya (Parrotomyia) africanus
      Newstead, S. (Sergentomyia) antennatus Newstead, S. (Spelacomyia) garnhami
      Heisch, Giggisberg & Teedale, S. (Rondanomyia) ingrami Newstead, and S.
      (Sergentomyia) schwetzi Adler, Theodor & Parrot, collected in the field in Kenya
      or reared in the laboratory. The patterns showed both quantitative and
      qualitative differences among species. Discriminant analysis of easily identified
      peaks (expressed as percentages of total peak area) confirmed the uniqueness of
      the pattern for each species. Species identifications of field-collected flies
      revealed an excellent correspondence between morphometric criteria and gas
      chromatography for all species, except P. duboscqi. These results indicated that
      the morphological criteria for the identification of P. duboscqi should be
      reexamined. Chromatograms of females and males showed slight quantitative
      differences.

PMID- 9775609
TI  - Oviposition attraction and repellency of Aedes aegypti (Diptera: Culicidae) to
      waters from conspecific larvae subjected to crowding, confinement, starvation, or
      infection.
AB  - As the biomass of Aedes aegypti (L.) larvae increased in relation to the volume
      of rearing waters, oviposition attraction of these waters to conspecific, gravid
      females first rose to a peak and then declined. Further increases in biomass
      rendered waters strongly repellent. Comparable responses were elicited by a
      decrease in the volume of rearing waters or an increase in the relative size or
      number of mosquito larvae. Low volumes of water reduced oviposition attraction
      and increased repellency, whereas larger volumes increased attraction.
      Excessively large volumes diluted attraction to neutrality. Constraints imposed
      by the physical dimensions of the larval environment which interfered with the
      normal postural movements and behaviors of the larvae also induced repellency,
      independent of rearing volume. Titration of repellent waters revealed that
      infection with the digenean Plagiorchis elegans (Rudolphi) generated the most
      powerful repellent effect, whereas crowding or starvation induced significantly
      weaker responses. At no time did dilution of repellent waters restore attractive
      properties. Repellents, even at minute concentrations, overrode attractants. The
      density-dependent action of oviposition attractants and repellents may help to
      maintain larval populations near optimal levels through their influence on
      recruitment. Oviposition repellency induced by sublethal infections with P.
      elegans may maintain population levels below the carrying capacity of the
      environment. Persistence of oviposition attraction and repellency varied
      inversely with temperature. The magnitude of the repellent effect induced by
      larvae appears to be a good indicator of their probability of survival and may be
      of selective significance. Repellency may deflect ovipositing females away from
      sites close to human habitation and may lead to new, and perhaps more effective,
      method, to control mosquitoes and the diseases they transmit.

PMID- 9775610
TI  - Morphology and development of Anaplasma marginale (Rickettsiales:
      Anaplasmataceae) in cultured Ixodes scapularis (Acari: Ixodidae) cells.
AB  - Anaplasma marginale Theiler, a tick-borne rickettsial pathogen of cattle, was
      recently propagated in a continuous tick cell line, IDE8, derived from embryonic
      Ixodes scapularis Say. Cell monolayers were infected briefly with a high
      multiplicity of infection to synchronize rickettsial development and allow for
      description of the invasion, development, and release of A. marginale from the
      cultured cells. Sequential samples were collected, fixed, and processed for
      examination with light and electron microscopy. A. marginale entered host cells
      by an endocytotic process and remained within a vacuolar membrane throughout
      development. After entry, the dense form of A. marginale transformed into the
      vegetative or reticulated form that multiplied by binary fission, forming large
      colonies of rickettsiae. The reticulated form subsequently transformed into the
      dense form of A. marginale, which was released from cells and survived
      extracellularly. The dense forms were eventually released from the cultured cells
      by a process in which the inclusion membrane fused with the host cell membrane.
      Release of A. marginale was effected without the loss of host cell cytoplasm. In
      subsequent cell cycles, A. marginale reinfected cultured cells resulting in the
      development of multiple colonies per cell and eventual host cell destruction.
      Small vesicles were abundant within the colonies and appeared to form from
      individual rickettsiae. Development of A. marginale in IDE8 cells was similar to
      that described in naturally infected Dermacentor spp. ticks. However, destruction
      of cells by A. marginale as seen in vitro was not observed in naturally infected
      ticks. An understanding of the developmental cycle of A. marginale in cultured
      cells may provide insight into rickettsial development in its tick host and
      provide a basis for studying pathogen-host cell interaction in vitro.

PMID- 9775611
TI  - Mortality of horn fly (Diptera: Muscidae) larvae in bovine dung supplemented with
      loline alkaloids from tall fescue.
AB  - Larvae of arthropod ectoparasites of livestock, such as the horn fly, Haematobia
      irritans (L.), may be exposed to acyl-loline alkaloids in dung of ruminant
      livestock ingesting herbage of the tall fescue (Festuca arundinacea Schreb.)
      endophyte association [Neotyphodium coenophialum (Morgan-Jones & W. Gams) Glenn,
      Bacon & Hanlin comb. nov.]. Biological activity of alkaloid-supplemented bovine
      dung was assayed by growth, development, and survival of 1st instars of horn fly.
      An extract from tall fescue seed, containing N-formyl loline (NFL), N-acetyl
      loline (NAL), and loline (59:21:20 by mass, respectively) caused 100% mortality
      of horn fly larvae when dung was supplemented at > or = 100 micrograms/g. Probit
      analysis of data corrected for natural mortality indicated a LD50 of 30
      micrograms/g (95% fidicial limits: 20-49 micrograms/g). When horn fly larvae were
      introduced to dung supplemented with up to 50 microM of acyl-loline derivatives,
      mortality of larvae varied significantly between alkaloids (P < 0.0001). Probit
      analysis indicated that NFL [LD50: 34 microM (95% fidicial limits: 3-53 microM)]
      was more toxic than NAL [LD50: 46 microM (0-83 microM)], and that loline
      hydrochloride was not toxic.

PMID- 9775612
TI  - Reservoir competence of the meadow vole (Rodentia: Cricetidae) for the Lyme
      disease spirochete Borrelia burgdorferi.
AB  - The reservoir competence of the meadow vole, Microtus pennsylvanicus Ord, for the
      Lyme disease spirochete Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt &
      Brenner was established on Patience Island, RI. Meadow voles were collected from
      5 locations throughout Rhode Island. At 4 of the field sites, M. pennsylvanicus
      represented only 4.0% (n = 141) of the animals captured. However, on Patience
      Island, M. pennsylvanicus was the sole small mammal collected (n = 48). Of the
      larval Ixodes scapularis Say obtained from the meadow voles on Patience Island,
      62% (n = 78) was infected with B. burgdorferi. Meadow voles from all 5 locations
      were successfully infected with B. burgdorferi in the laboratory and were capable
      of passing the infection to xenodiagnostic I. scapularis larvae for 9 wk. We
      concluded that M. pennsylvanicus was physiologically capable of maintaining B.
      burgdorferi infection. However, in locations where Peromyscus leucopus
      (Rafinesque) is abundant, the role of M. pennsylvanicus as a primary reservoir
      for B. burgdorferi was reduced.

PMID- 9775613
TI  - Life table study of Aedes aegypti (Diptera: Culicidae) in Puerto Rico fed only
      human blood versus blood plus sugar.
AB  - Life table studies were performed in 1996 with Aedes aegypti (L.) during the low
      (cool/dry) and high (hot/rainy) dengue virus transmission seasons in Puerto Rico.
      Mated adult females from field-collected pupae were placed individually in cages
      and divided into 2 treatment groups: one was fed only human blood and the other
      human blood plus a 10% sucrose solution. Survival and number of eggs laid were
      recorded daily for each female. During both seasons, age specific survivorship
      was higher for the blood plus sugar group, groups fed only human blood had higher
      reproductive outputs (mx), and net replacement rates (Ro) for blood only groups
      were higher than for those fed blood plus sugar. Intrinsic rates of growth (r)
      were the same for both treatments during the low (cool/dry) transmission season,
      but higher for the blood-only treatment during the high (hot/rainy) transmission
      season. Our results indicate that feeding on only human blood provides an
      evolutionary advantage to Ae. aegypti females in Puerto Rico. These results are
      similar to those from an earlier study carried out with Ae. aegypti in Thailand;
      the advantage of feeding on human blood does not seem to be restricted to a
      particular geographic region. We also found that the benefits associated with
      human feeding persist through epidemiologically different times of the year. We
      conclude that feeding on human blood is reproductively beneficial for Ae.
      aegypti, which may increase their contact with human hosts, and therefore may
      influence their vectorial capacity for dengue viruses through frequent feeding on
      blood.

PMID- 9775614
TI  - Laboratory studies of susceptibility and resistance to insecticides in Pediculus
      capitis (Anoplura; Pediculidae).
AB  - The susceptibility of local head lice to permethrin, sumithrin, deltamethrin, and
      carbaryl was determined by laboratory bioassays in field-collected colonies. Head
      lice collected from the infested heads of children 6-12 yr old were tested within
      3 h of collection. The longest survival of control insects in the laboratory was
      obtained by keeping them in the dark at 18 degrees C and 70-80% RH. The base line
      susceptibility data obtained for insects collected from children not treated for
      lice, the reference colony, showed that deltamethrin caused the highest mortality
      of the insecticides tested (LC50, 0.06%). Permethrin, sumithrin, and carbaryl
      showed no significant difference in mortality (superposition of confidence
      intervals), being 10 times lower than that caused by deltamethrin. All field
      collected lice required a higher LC50 of permethrin than the reference colony.
      Resistance levels varied from 3 to > 100 for colonies that were taken from
      children treated with anti-lice products. Lice colonies with permethrin
      resistance showed resistance to sumithrin and deltamethrin, but resistance was
      not observed to the carbamate carbaryl.

PMID- 9775615
TI  - Culicoides variipennis (Diptera: Ceratopogonidae) complex in Virginia.
AB  - Immature Culicoides variipennis (Coquillett) were sampled from aquatic habitats
      throughout Virginia, reared to adults, and examined by isozyme electrophoresis to
      assess their taxonomic status. Data from 22 counties showed that C. v.
      variipennis is widespread and common, the predominant taxon throughout Virginia,
      and genetically similar to C. v. variipennis in Maryland. Because C. v.
      variipennis is considered an inefficient vector of the bluetongue viruses, this
      observation is consistent with the low seroprevalence of bluetongue in indigenous
      livestock of the mid-Atlantic region. Culicoides v. sonorensis Wirth & Jones,
      considered to be the primary North American vector of the bluetongue viruses, was
      recovered in large numbers only from a wastewater lagoon at a dairy in
      southeastern Virginia, but also was detected at low levels in 6 other counties.
      Comparison of genetic distances and patterns of discriminating alleles among
      Virginia populations of C. v. variipennis and C. v. sonorensis showed that
      respective subspecies are genetically distinct and show no evidence of
      introgression, irrespective of geographic- and habitat-level sympatry. The
      persistence of a pure C. v. sonorensis population in a dairy wastewater lagoon
      may reflect physico-chemical factors that influence the distribution of immature
      C. variipennis complex populations. A better understanding of the distribution of
      the C. variipennis complex will benefit regionalization of U.S. exports of
      livestock and livestock germplasm to bluetongue-free countries.

PMID- 9775616
TI  - Density dependence in larval Aedes albopictus (Diptera: Culicidae).
AB  - Aedes albopictus (Skuse) is expanding its distribution in the United States and
      elsewhere, and a better understanding of its population regulation is needed. A
      field experiment under seminatural conditions determined that density had a
      negative effect and food level a positive effect on immature survival, duration
      of development, and female size at emergence. A summary index (r') indicated that
      population growth also depended on density and food availability. These data can
      be used to estimate the relationships needed in the development of mathematical
      models for Ae. albopictus.

PMID- 9775617
TI  - Morphological, molecular, and chromosomal discrimination of cryptic Anopheles
      (Nyssorhynchus) (Diptera: Culicidae) from South America.
AB  - Based on similarity of male genitalia, the malaria vector Anopheles trinkae Faran
      from the eastern Andean piedmont of Colombia, Ecuador, Peru, and Bolivia was
      determined by Peyton (1993) to be a junior synonym of An. dunhami Causey, then
      known from a single locality in Amazonian Brazil. Following an appraisal of
      molecular, chromosomal, and morphological characters, we conclude herein that the
      2 taxa are specifically distinct and remove An. trinkae from synonymy with An.
      dunhami. Eggs of the 2 species are distinguished easily by the anterior crown,
      long floats, and closed deck that occur only in An. trinkae. The X chromosome of
      larval polytenes is divisible into R and L arms in An. dunhami, but not in An.
      trinkae. A phenogram based on banding pattern scores from 18 random amplified
      polymorphic DNA primers separated with 100% resolution An. dunhami, An. trinkae,
      Anopheles nuneztovari Gabaldon and Anopheles darlingi Root. In the ITS2 region of
      rDNA, 25% of base sites distinguished An. trinkae from An. dunhami and 21% from
      the related An. nuneztovari; males of these 3 species had accessory glands of
      significantly different sizes. Preliminary isoenzyme screening indicated that 3
      of 11 loci were diagnostic for separating An. trinkae from An. dunhami. The
      results indicate that An. dunhami is related more closely to An. nuneztovari than
      to An. trinkae and illustrate the merits of a multidisciplinary approach to
      mosquito systematics.

PMID- 9775618
TI  - Effects of sodium concentration on Aedes triseriatus (Diptera: Culicidae) and
      microorganisms in treeholes.
AB  - A 2-factor field microcosm experiment with 2 concentrations of sodium ([Na]) was
      performed with and without mosquitoes to test the hypothesis that Na is a
      limiting nutrient for the treehole mosquito, Aedes triseriatus (Say), at
      concentrations observed in the field. This experiment also tested the effects of
      both water [Na] and mosquito larvae on cohabiting treehole microorganisms. Female
      Ae. triseriatus emerging from microcosms with high-[Na] were significantly larger
      than females emerging from low-[Na] microcosms. There was no effect of [Na] on
      the size of males; however, males had higher body [Na] than females at both [Na].
      Densities of protozoans were lower in the presence of mosquitoes, and densities
      of bacteria were lower at high than low [Na]. Water [Na] may affect mosquito
      populations by decreasing energy expenditures to obtain Na at higher [Na],
      allowing for more allocation to growth. Males were not affected by the [Na]s
      tested here. This experiment agrees with field observations and other laboratory
      studies indicating that [Na] may affect populations of Ae. triseriatus under
      certain conditions.

PMID- 9775619
TI  - Comparisons of rice field mosquito (Diptera: Culicidae) abundance among areas
      with different agricultural practices in northern Thailand.
AB  - Adult mosquitoes were collected from 3 areas in northern Thailand with different
      availabilities of rice fields for larval habitats by using blacklight, truck, and
      pig-baited traps. Culex tritaeniorhynchus Giles and Culex gelidus Theobald were
      dominant in all samples. Significant study-area differences were found in light
      and truck trap collections for Cx. tritaeniorhynchus and Cx. gelidus, but not for
      Culex vishnui Theobald + Culex pseudovishnui Colless. In pig-baited sample area
      differences were significant only for Cx. gelidus. Adults of Culex fuscocephala
      Theobald were relatively rare, comprising only 0.6-7.9% of the total mosquitoes
      collected. When compared with the results from previous studies in the Chiangmai
      area, we conclude that Cx. fuscocephala has become a minor species and that
      changes in the mosquito fauna have occurred in northern Thailand.

PMID- 9775620
TI  - Kinetics and cross-species comparisons of host antibody responses to lone star
      ticks and American dog ticks (Acari: Ixodidae).
AB  - Understanding of the animal antibody response to tick salivary gland proteins is
      necessary to identify candidate antibodies that may have use as species- and
      feeding-duration-specific biomarkers of tick exposure in humans. The kinetics of
      the humoral immune response of rabbits to challenge feeding by 2 tick species
      [Amblyomma americanum (L.) and Dermacentor variabilis (Say)] was characterized by
      both enzyme-linked immunosorbent assay and immunoblot. Western blot analysis
      revealed that rabbits produced antibodies against both A. americanum and D.
      variabilis tick salivary gland antigens, with molecular weights ranging from 12.2
      to 125 kDa; the antibody response against the saliva of both tick species
      possessed both unique and common aspects. The presence of antibody against low
      molecular-mass (< 20 kDa) salivary gland antigens of A. americanum may be
      specific for A. americanum exposure. Antibodies directed against D. variabilis
      salivary gland antigens of 111, 86.3, and 85 kDa may be specific for D.
      variabilis exposure. The data suggest that host antibodies directed against
      specific tick salivary gland proteins might have use as species-specific biologic
      markers of tick exposure.

PMID- 9775621
TI  - Two new species of chiggers (Acari: Trombiculidae and Leeuwenhoekiidae) from
      Iran.
AB  - Odontacarus khanjani Goff & Saboori (Leeuwenhoekiidae) and Neotrombicula
      iranensis Goff & Saboori (Trombiculidae) were described as new. Both species were
      collected as unengorged larvae on alfalfa plants, Medicago sativa, in western
      Iran.

PMID- 9775622
TI  - Evaluation of natural Psoroptes ovis (Acarina: Psoroptidae) soluble proteins as
      candidate vaccine immunogens.
AB  - In this study potential vaccine candidate immunogens were identified and
      evaluated in a vaccine challenge trial. Calves vaccinated with a partially
      purified fraction of Psoroptes ovis-soluble proteins had 8 of 14 calves free of
      palpable lesions 8 wk after a challenge infestation. A self-grooming behavioral
      response elicited by a pruritic immediate-type allergic reaction was believed to
      be an effector in protecting the vaccinated calves from a clinical P. ovis
      infestation.

PMID- 9775623
TI  - Geographic distribution of ticks (Acari: Ixodidae) in Michigan, with emphasis on
      Ixodes scapularis and Borrelia burgdorferi.
AB  - A 12-yr (1985-1996) passive survey in Michigan based upon tick submissions from
      citizens yielded 4,755 ticks of 21 species, 16 of which were probably indigenous
      in the state. Three species of Dermacentor [most common, D. variabilis Say and D.
      albipictus (Packard)]; 2 species of Amblyomma [most common, A. americanum (L.)];
      and 12 species of Ixodes (most common, I. cookei Packard and I. scapularis Say),
      as well as Haemaphysalis leporispalustris (Packard), Rhipicephalus sanguineus
      Latreille, and the soft ticks Ornithodoros kelleyi Cooley & Kohls, and Otobius
      megnini (Duges) were submitted. New state records were I. kingi Bishopp, I.
      texanus Banks, I. sculptus Neumann, and I. baergi Cooley & Kohls. Examination of
      gut smears from dissections of 1,037 ticks of 13 species by indirect
      immunofluorescent assay, using murine monoclonal H9724 as the primary antibody,
      revealed that 11 of 175 I. scapularis were infected with Borrelia spp. All
      positive I. scapularis were from Menominee County in the upper peninsula of the
      state, which also provided 79.8% of all submitted I. scapularis. Surveys for
      ticks on 5,449 hunter-killed white-tailed deer were conducted from 1988 to 1990,
      encompassed deer taken from 65 of the state's 83 counties, and showed that
      although D. albipictus was distributed widely in the northern part of the state,
      I. scapularis occurred only on deer taken from southern townships of Menominee
      County. Of 1,218 canine sera tested for antibodies to B. burgdorferi in 1992 and
      1993, 25 of 299 (8.0%) from Menominee County were positive but only 1 of 919 sera
      submitted from 5 counties in the lower peninsula was positive.

PMID- 9775624
TI  - Taxonomic study of the genus Ctenocephalides Stiles & Collins, 1930 (Insecta:
      Siphonaptera: Pulicidae) by using aedeagus characters.
AB  - To define more accurately the taxonomic position of the species of
      Ctenocephalides Stiles & Collins, 1930 (Siphonaptera), a morphological study of
      the aedeagus was conducted an all taxa of this genus. Based on some phallosome
      structures (hamulus, lobes, tubus interior), an identification key is constructed
      to complement the existing taxonomic criteria. C. orientis and C. damarensis are
      confirmed to specific rank.

PMID- 9775625
TI  - Recognition of the tick genus Anocentor Schulze, 1937 (Acari: Ixodidae) by
      numerical taxonomy.
AB  - We report on an evaluation of the systematic position of the tick Anocentor
      nitens (Neumann), examining particularly whether Anocentor should be regarded as
      a subgenus of Dermacentor or as a separate genus. Twelve species of Ixodidae were
      analyzed phenetically by using 24 characters of adult ticks. A phenogram
      indicated 3 clusters, with Anocentor more closely related to Rhipicephalus than
      to Dermacentor. The results of this study endorse the validity of the monotypic
      genus Anocentor.

PMID- 9775626
TI  - Comparison of genomic DNA in various strains of Boophilus microplus (Acari:
      Ixodidae).
AB  - The conventional method of identifying acaricide resistance in a suspect tick
      population by the United Nations Food and Agriculture Organization packet assay
      is a laborious and time-consuming process. DNA probes have been demonstrated as
      rapid and accurate tools for detecting pesticide resistance in insect species.
      Random-amplified polymorphic DNA (RAPD) has been used by other groups to
      differentiate species of mosquitoes and populations within a mosquito species. By
      using different arbitrary oligonucleotides as primers with RAPD, we have
      demonstrated that various strains of Boophilus microplus (Canestrini) show
      different patterns of DNA fragments on agarose gel electrophoresis. The unique
      DNA fragments may be useful for developing probes that can detect acaricide
      resistance in field pest populations.

PMID- 9775627
TI  - Coinfection of blacklegged ticks (Acari: Ixodidae) in Dutchess County, New York,
      with the agents of Lyme disease and human granulocytic ehrlichiosis.
AB  - Adult blacklegged ticks, Ixodes scapularis Say, collected from forested sites in
      Dutchess County, NY, were tested for infection with the etiologic agents of Lyme
      disease, Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner, and
      human granulocytic ehrlichiosis (HGE). Rates of infection with the 2 pathogens
      were high and independent of one another, confirming prior findings and
      suggesting that a variety of hosts may be competent reservoirs of the HGE agent.

PMID- 9775628
TI  - The future: imagine the possibilities, Part II--health care.

PMID- 9775629
TI  - History. Delete or save?

PMID- 9775630
TI  - Education. Liberal learning in nursing education--connecting career with service.

PMID- 9775631
TI  - International affairs. Nurse education in the United Kingdom--Project 2010?

PMID- 9775632
TI  - Legal and ethical issues. Bioethics legislation.

PMID- 9775633
TI  - Faculty practice as partnership with a community coalition.
AB  - Faculty practice as partnership with a community coalition can be a dynamic
      strategy for retooling the future of nursing. The Escalante ElderCARE Coalition
      was formed in 1991, with the Community Health Division of the Arizona State
      College of Nursing taking a leadership role. Since that time, more than 50 aging
      network and community agencies have become involved. More than $300,000 in grant
      funding has been awarded for Healthy WAY services with low-income seniors as
      health care and program partners. The conceptual model includes health-promotion
      services, participation of community elders in program planning and evaluation,
      and education of health professionals. Participation theory is the basis for the
      conceptual model. A large number of undergraduate and graduate nursing students
      have been involved in the nontraditional delivery of services provided by the
      coalition. The Short Form 36 (SF-36) and the Lifestyle Directions Questionnaire
      are the health status outcome measures, and elder satisfaction, coalition
      effectiveness, and cost-savings measures are the process indicators. Elders
      reported healthier scores in six of the eight SF-36 dimensions, including general
      health, than the older US general population, but they also report that their
      amount of physical exercise and fiber intake is less than adequate. Overall, the
      elders express great satisfaction with the Healthy WAY programs but do not
      perceive as much ownership as do the coalition's agency professionals. Coalitions
      are emerging as a force for change and a public health strategy, and faculty
      members are encouraged to take seriously the opportunities afforded by them for
      proactive, advanced practice roles.

PMID- 9775634
TI  - Preparing for the 21st century: diversity in nursing education, research, and
      practice.
AB  - This article presents issues surrounding nursing research, education, and
      practice as they relate to the changing demographics in American society. The
      authors suggest that cultural diversity should be a key element in all components
      of nursing. They present challenges to nurse researchers, educators, and
      practitioners regarding the essential need to be sensitive about cultural
      diversity. They further suggest that the 21st century will emerge with
      demographic shifts that include larger groups of ethnic individuals and families.
      These ethnic groups will be both care providers and recipients of care.
      Recommendations are suggested to prepare for diversity in America health care
      systems.

PMID- 9775635
TI  - Developing a culturally competent work force: an opportunity for collaboration.
AB  - This article describes a collaborative project formed between three major
      community systems--education, health care, and the business sector--to respond to
      the specialized cultural needs of a growing Hispanic population in a large public
      health care system in Dallas, TX. Two specific strategies, short-term cultural
      immersion and the development of a nurse exchange program with a "sister"
      hospital in Mexico, assist health care personnel to learn the language and the
      culture of Mexico. Findings from process evaluation suggest that these
      initiatives are essential and beneficial to changing individual views and
      developing knowledge and skills. Community partnerships requiring a significant
      commitment to a continuum of efforts from top administrative levels to the
      individual level facilitate institutional responses to the challenge of
      developing a culturally skilled health work force.

PMID- 9775636
TI  - Nurse educators'/administrators' ways of handling conflict.
AB  - Using women's standpoint research to analyze the data, a qualitative,
      retrospective case study was undertaken to study the group process among 27
      female nurse educators/administrators who met from 1987 to 1990. The group was
      engaged in making major changes to integrate nursing education programs from a
      variety of institutions. Part of the research involved studying the group's
      conflict-handling strategies. These strategies were compared and contrasted with
      strategies found in traditional, feminist, and nursing management literature. In
      the traditional management literature, five conflict-handling modes are
      described: competing, compromising, avoiding, integrating, and accommodating.
      Although the research results indicated similarities between the conflict
      handling modes used by the group studied and those reported in the research
      literature, there also were significant differences. One unique strategy
      identified was not competing. Competing as a strategy was rejected. Compromising
      and avoiding were used frequently by the group. Integrating, the most efficacious
      strategy, was used to resolve only two issues, whereas accommodating was not
      identified as an obvious strategy, although two aspects of it were apparent. One
      conclusion is that conflict management theories based on men's behavior do not
      adequately explain nurses' (women's) conflict management behavior. This study
      suggests that nurse educators/administrators may have a distinct approach to
      conflict management that has not been recognized.

PMID- 9775637
TI  - How to develop and sustain a peer-mentored research work group.
AB  - Most collaborative research models in nursing focus on hierachical structures in
      which an identified expert or leader directs and/or guides others in conducting
      research. The authors propose a peer-mentored model of collaborative research
      that promotes collegial participation, maximizes the use of each member's
      expertise, and enhances skill development within the group. This article is a
      description of the evolution of the Dementia Research Work Group within the
      Decker School of Nursing at Binghamton University. Emphasis is placed on how to
      create and nurture a peer-mentored research work group as well as what has been
      learned from the process.

PMID- 9775638
TI  - Entry into community-based nursing practice: perceptions of prospective
      employers.
AB  - To better prepare new graduates for entry-level positions in community settings,
      faculty of one college of nursing gathered information using focus groups of
      prospective employers. The groups were to identify the skills and qualities
      nurses need to practice in the community and ways to redesign nursing curricula
      to better prepare undergraduates for community-based practice. Data for this
      qualitative study were collected in five separate focus groups conducted with
      prospective employers (N = 18) from four major areas of Kentucky. By
      collaborating with prospective employers in the community, a partnership was
      established between nurse educators and community health leaders to improve the
      marketability of baccalaureate graduates. Assessment was the most frequently
      named skill essential to nursing practice in the community. Independence,
      critical thinking, collaboration, and confidence consistently emerged as
      important skills and qualities. Prospective employers were positive about
      developing partnerships to improve under-graduate nursing curricula.
      Recommendations for curricula to better prepare undergraduates for community
      based practice are suggested.

PMID- 9775639
TI  - Educational mobility. American Association of Colleges of Nursing.
AB  - POSITION STATEMENT: As health care shifts from a fragmented system of disparate
      providers and payers into integrated managed systems, nurses and other health
      professionals are encountering tremendous changes. The environments in which
      nurses practice are becoming increasingly diverse, and the skills required to
      practice in these settings are becoming increasingly specific to the services
      offered and the patients served. Advances in health-related technologies call for
      enhanced knowledge and application of computing and other technical skills.
      Nurses are faced with complex ethical dilemmas created by rationing-of-health
      care decisions and research advances such as the human genome project. Practicing
      nurses must continue to update their skills as their work environments adapt to
      reforms in health care delivery. Furthermore, nurses' practice will be influenced
      by changes in the regulatory system that will accompany multistate recognition of
      licensure. Over the years, the nursing educational system, through multiple entry
      and exit routes, has prepared nurses for the variety of settings in which health
      care is delivered. The nursing educational system must continue to produce the
      most qualified and prepared nurses to produce the most qualified prepared nurses
      to deliver cost-effective and quality care. Nurse educators must continue to
      analyze health care trends and create flexible curricula that provide individuals
      with the skills and knowledge needed for diverse settings. Furthermore, nurse
      educators must continue to offer continuing education for nurses as they fine
      tune skills for new settings. Educational mobility in nursing is the vehicle by
      which nurses and aspiring nurses gain new knowledge and skills through formal and
      informal educational offerings. Educational mobility serves the public, the
      profession, and the individual nurse. Educational mobility should continue to
      focus on promoting high standards and maintaining the quality and integrity of
      baccalaureate and graduate programs while emphasizing the attainment of program
      outcomes. The focus of higher learning should be on the socialization of students
      to new professional roles and the knowledge and skills needed for these roles.
      Educational mobility options should respect previous learning that students bring
      to the educational environment. To this end, educational mobility encompasses
      diverse approaches to continuous, life-long learning for nurses and for
      individuals aspiring to nursing as a profession. Baccalaureate and higher-degree
      programs in nursing should build on knowledge and skills attained by learners
      before their matriculation into formal educational programs. Higher education in
      nursing should be offered using creative and flexible approaches that are
      incorporated into curricula and reflect consideration of individual student
      learning needs.

PMID- 9775640
TI  - Nightguard vital bleaching: a review and clinical study.
AB  - Based on current clinical experience and research, dentist-prescribed home
      bleaching, also referred to as nightguard vital bleaching, is a safe and
      effective technique for whitening teeth when a carbamide peroxide material (up to
      10 percent) is used. The bleaching material should be produced by a recognised
      and reputable manufacturer and must be used under a dentist's supervision over a
      relatively short time. Mild thermal sensitivity is a common side effect; however,
      no long-term pulpal effects have been shown. The reduction in the bond strength
      of resin to freshly bleached enamel and dentine has been shown to be transient,
      and no clinically significant changes in surface morphology or physical
      properties have been shown to occur to teeth or dental restorative materials as a
      result of vital bleaching. As a consequence, vital bleaching has gained favour
      with patients and dentists alike. Significant benefit was obtained in 12 subjects
      using two nightguard bleaching systems which were equally effective.

PMID- 9775641
TI  - Documenting the changing face of New Zealand.
AB  - This paper reviews the major descriptive dental epidemiological surveys that have
      taken place in New Zealand, and discusses the role of Dr TW Cutress in their
      initiation, organisation, and implementation. The study that has had the major
      impact was the 1976 Survey of Adult Oral Health, which had two main findings.
      First, teenagers had a high number of restored teeth, little untreated decay, and
      few extractions of permanent teeth, regardless of social or ethnic group. Second
      was the high rate of extraction of permanent teeth in adults. The survey findings
      created debate and intense activity in dental circles. A second national study,
      the World Health Organization's Study of Oral Health Outcomes, demonstrated that,
      by 1988, oral health had improved in all age groups. In the space of a little
      over a decade, the population had gone from having one of the highest levels of
      dental disease to a low disease level in children and marked reductions in tooth
      loss in adults. A further national survey is recommended to take place in the
      year 2000.

PMID- 9775642
TI  - The decline of caries in New Zealand over the past 40 years.
AB  - In New Zealand, as elsewhere, caries prevalence has declined since the 1950s;
      this has been accompanied by a change in the intra-oral pattern of the disease.
      This is illustrated by analysis of data for 12-year-old children. However,
      because treatment services for children in New Zealand are so comprehensive, the
      DMF index is primarily a count of restorations placed. This treatment overlay can
      distort the true caries prevalence and has been a confounding factor in
      assessment of the change in caries over time. Measurement of the fine gradations
      of ongoing change in the present low-caries-prevalence population requires the
      use of a more sensitive indicator than the DMF indices. When the timing of
      various forms of fluoride supplementation is correlated with the decline in
      caries, the decline continues beyond the time of maximum population coverage with
      fluoridated water and fluoridated toothpaste. Thus an explanation of the
      convergance of caries prevalence in fluoridated and non-fluoridated areas since
      the 1970s may require a re-assessment of the fluoride effect. This convergence,
      and the overall decline during the last decade without known additional fluoride
      supplementation, suggest that factors other than fluoride, such as food additives
      and antibiotics, may have contributed.

PMID- 9775643
TI  - Soils and dental research.

PMID- 9775644
TI  - Cytokines in the developing periodontal tissues of rats.

PMID- 9775645
TI  - Pathways to organogenesis: from coconut crazed teeth in Tonga to salivary glands
      in space.

PMID- 9775646
TI  - The origins and development of the Community Periodontal Index of Treatment
      Needs.

PMID- 9775647
TI  - The Community Periodontal Index of Treatment Needs--uses and abuses?
AB  - The CPITN system has undergone modifications to enable it to be used for the
      screening of patients in general practice. Many of the features of the original
      index are retained. The modifications overcome some of the concerns raised by
      critics of CPITN by allowing recession and furcation defects to be recorded. The
      widespread use of the modified Index indicates that it has a useful role to play
      in the diagnosis and management of periodontal diseases, and is a tribute to its
      original design.

PMID- 9775648
TI  - The contributions of Terry Cutress from the perspective of the dental profession.

PMID- 9775649
TI  - Treatment of obstructive sleep apnoea in edentulous patients--design of a
      combination appliance: a case study.
AB  - This report describes the fabrication of a prosthesis to prevent obstructive
      sleep apnoea in edentulous patients. The objective of treatment in a 62-year-old
      man was to establish a comfortable protrusive and vertical position of the
      mandible that minimised hypopharyngeal obstruction nocturnally. An appliance was
      designed incorporating two concepts in the elimination of obstructive sleep
      apnoea: mandibular advancement, which maintains hypopharyngeal width nocturnally;
      and advancement of the tongue with the aid of a device holding the tongue in a
      protrusive position by vacuum pressure. This combination appliance offers a
      treatment modality to a large group of otherwise forgotten patients.

PMID- 9775650
TI  - Dental management of people with renal disease and renal transplants.
AB  - Chronic renal failure is the result of progressive loss of functioning nephrons
      leading to loss of renal function and accumulation of excretory products. Loss of
      the regulatory and excretory functions of the kidneys causes oral manifestations
      and multiple complications which have implications for dental care. Dental
      management of patients with renal failure and renal transplants involves
      consideration of specific haematological and cardiovascular effects, and
      implications for the prescribing and use of pharmaceuticals. It also requires the
      dentist to appreciate the potential for involvement of multiple organ systems in
      the disease process and the implications this has for dental care. The orofacial
      manifestations of chronic renal failure are secondary to systemic manifestations
      and are not specific to the diagnosis of end-stage renal disease.

PMID- 9775651
TI  - Care of psychiatric patients.

PMID- 9775652
TI  - [Complex treatment of infected necrotizing pancreatitis].
AB  - Pancreatic necrosis associated with septic conditions is the leading cause of
      mortality in acute pancreatitis. Since 1986, 155 patients with infected
      pancreatic necrosis have been treated. The mean APACHE II score was 18.5 (range
      11-32). In all cases, the infected pancreatic necrosis was combined with
      retroperitoneal abscesses. The surgical treatment was performed on average 18.5
      days (range 8-25 days) after the onset of acute pancreatitis. The operative
      management consisted of wide-ranging necrosectomy in the total affected area,
      combined with widespread lavage and suction drainage. In 69 of the 155 cases
      (45%), some other surgical intervention (distal pancreatic resection,
      splenectomy, cholecystectomy, sphincteroplasty or colon resection) was also
      performed. Following surgery supportive therapy was applied in all patients,
      which also consisted orf immunonutrition (glutamine and arginine supplementation)
      and modification of cytokine production by petoxyfillin and dexamethasone from
      1992. TNF and IL-6 serum levels were measured by ELISA and in vitro stimulation
      of leukocytes were induced by E. coli LPS. Following surgery, continuous lavage
      and suction drainage were applied for an average of 41.5 days (range 21-90 days),
      with an average of 9.5 (range 5-20) litres of saline per day. The bacteriologic
      findings revealed mainly enteral bacteria, but Candida infection was also
      frequently detected. The incidence of fungal infection was 20%. Thirty-two
      patients (21%) had to undergo reoperation. The cytokine production capacity (TNF
      and IL-6) was shown to correlate with the prognosis. As a consequence of
      pentoxifyllin and dexamethasone therapy, the TNF production generally dropped to
      the normal level. The overall hospital mortality was 6.4% (10 patients died). In
      our experience, infected pancreatic necrosis responds well to aggressive surgical
      treatment, continuous, long-standing lavage and suction drainage, together with
      supportive therapy consisting of immunonutrition and modification of cytokine
      production, combined with adequate antibiotic and antifungal medication.

PMID- 9775654
TI  - [Regional differences in suicide in Hungary in the light of registered cases of
      depression].
AB  - Author made a revision on the theory published by Rihmer and alii in the year
      1989. According to this theory the marked regional differences of suicide in
      Hungary are caused by the different discovery of the "endogen depression" (rate
      of diagnosed depression). So the lower is the diagnosis of depression the higher
      is the suicide rate in a given territory. They have seen a negative correlation
      between the number of working physicians and the suicide rates. Author made a
      reexamination on a correct database between 1985-1994. He has also made a study
      using the DSM-III-R diagnostic criteria in four counties of Hungary. His results
      deny the theory above mentioned. The rank-correlation of the number of GP and the
      suicide rates in Hungary in years 1985-1994 did not show correlation. So the
      underdiagnosis of the depressive disorders and the different number of GP are not
      the cause of the regional differences of suicide in Hungary.

PMID- 9775653
TI  - [Current viewpoints on the evaluation of testicular biopsy].
AB  - The aim of this study was to analize clinical diagnoses and histopathological
      reports in 185 cases of male infertility, investigated by testicular biopsies in
      the period 1993-1997. The classical objective of such investigations has been to
      clarify either obstructive, or so-called secretory lesions resulting in
      azoospermia. Histologically normal spermatogenesis was reported in 8 patients
      (4.3%). Hypospermatogenesis proved to be the most frequent pathologic lesion (69
      cases, 37.3%), followed by maturation arrest (61 cases, 33%). Germ cell aplasia
      (Sertoli-cell-only syndrome) was found in 28 cases (15.1%). Tubular atrophy was
      the dominant lesion in 5 cases (2.7%). Inflammatory change without other
      histologic abnormalities was seen only in 1 biopsy (0.5%). Further 13 specimens
      (7%) showed miscellaneous lesions, including one intratubular germ cell
      neoplasia. Retrospective histopathologic analysis revealed the coexistence of
      different basic lesions in 43 of our cases (21.7%). According to the novel
      requirements, pathologists should always report the presence of germ cell forms
      in the specimen, which are potentially suitable for fertilization. This is
      essencial because the new methods of testicular spermium extraction and
      intracytoplasmatic spermium injection offer the chance of assisted fertilization,
      even for some patients with smaller testicles and slightly elevated FSH levels.

PMID- 9775655
TI  - [New possibilities in the management of hemorrhagic diathesis caused by factor
      deficiency and thrombocytopenia: recombinant active factor VII concentrate].
AB  - Recombinant Factor VIIa, a new therapeutic tool to treat severe bleeding caused
      by inhibitory haemophilia cases, some cases of thrombocytopenia and
      thrombocytopathy (e.g. severe type III von Willebrand disease) receives growing
      attention in clinical practice. Exogeneous FVIIa-in a supraphysiological
      concentration (clearly over 6 U/ml) seems to be able to generate quickly and
      safely (without thrombotic side effects) thrombin--the final enzyme of clotting-
      in physiological, or pathological conditions. A concise review about the possible
      mechanisms of action, indications, monitoring and clinical experience gained
      sofar with FVIIa is given in this report.

PMID- 9775656
TI  - [Life-threatening gastrointestinal bleeding in Crohn disease].
AB  - Massive gastrointestinal bleeding is a very rare complication in Crohn's disease.
      Its occurrence has been quoted as 1-2% in the literature. A case of a 16-year old
      boy is reported here, who had a three-year history of Crohn's disease. After a
      three-day's therapy of bronchopneumonia a massive rectal bleeding began and an
      emergency operation had to be made. Site of the bleeding was localised by
      intraoperative colonoscopy and an ileocolic resection was made. The patient
      recovered and has done well since. Some characteristics, diagnostic and
      therapeutic problems of the massive bleeding in Crohn's disease are discussed.

PMID- 9775657
TI  - [In memoriam Karoly Leufenauer--on the 150th anniversary of his birth].

PMID- 9775658
TI  - [Lived: 64 years. History of the Benczur Street Hospital in Budapest (1931
      1995)].

PMID- 9775659
TI  - Pilot study of suicide risk factors among personnel in the United States Marine
      Corps (Pacific Forces).
AB  - Risk factors for suicide among active-duty members of the United States Marine
      Corps were investigated. Three groups were suicide attempters (n = 172),
      completers (n = 22), and a nonpsychiatric comparison group (n = 384). A series of
      multiple regression and discriminant analyses were conducted to assess whether
      any of 137 selected risk-factors differentiated the suicidal group from the
      comparison group. The following factors differentiated suicide attempters and
      completers from the comparison group and were associated with increased suicide
      risk: History of Abuse, Neglect, or Rejection, Lower Performance Evaluation,
      Symptoms of Depression, No History of Gambling Behavior, Younger Age, History of
      Alcohol Abuse, and Hopelessness. A discriminant analysis using these seven
      variables resulted in a 77% accuracy rate. When evaluating variables that could
      be obtained by a review of military records alone, three variables differentiated
      the attempters and completers from the comparison group, Lower Performance
      Evaluation, Younger Age, and a History of Military or Legal Problems. These
      variables correctly classified 73% of the sample. Implications for suicide-risk
      assessment for individuals in the Marine Corps are provided.

PMID- 9775660
TI  - Comprehensive review of biorhythm theory.
AB  - Biorhythm theory which became popular with the general public in the late 1960s
      held that three different biorhythm cycles influenced three different general
      aspects of human behavior. There was a 23-day cycle which influenced physical
      aspects of behavior. A 28-day cycle influenced emotions and a 33-day cycle
      influenced intellectual functions. Further, according to the theory, these three
      cycles started at birth and progressed, sinusoidally, throughout life varying not
      a bit with environmental or physiological factors. This paper reviews 134 studies
      of biorhythm theory, both published and unpublished. 35 of those reported some
      support for biorhythm theory. Careful examination of these studies identified
      methodological and statistical errors that account for the claimed findings
      supporting the theory. Another 99 studies, covering many different variables,
      yielded no support. The conclusion is that biorhythm theory is not valid.

PMID- 9775661
TI  - Revisiting sexual styles: patterns of adolescents' self-perceptions.
AB  - Recently, Buzwell and Rosenthal proposed that sexual styles were a useful way of
      understanding young people's constructions of a sexual identity. In this work we
      replicated with a sample of 522 15- to 16-yr.-olds in broad terms, the five
      styles identified by Buzwell and Rosenthal.

PMID- 9775662
TI  - Very delayed smoking relapse warrants research attention.
AB  - Recent findings suggest that former smokers remain at risk for relapse well
      beyond the traditional treatment follow-up period of one year. Although progress
      has been made in understanding factors involved in smoking cessation and short
      term maintenance, very little attention has been paid to research on the process,
      predictors, and treatment implications of very delayed relapse. Possible research
      questions are offered to stimulate further investigation in this area.

PMID- 9775663
TI  - The Manic Depressiveness Scale: a preliminary effort at replication and
      extension.
AB  - In a previous paper, an 18-item scale was presented to measure the extent to
      which a person had experienced symptoms resembling mania or clinical depression.
      There was evidence that, within a group of 37 bipolar persons, scores on this
      Manic Depressiveness Scale correlated significantly positively with number of
      manic-depression-relevant medications currently being taken by the subject. In
      the present study, 24 subjects (9 unipolar depressives, 15 bipolars) were
      administered this scale, and aspects of their clinical history were taken. For
      the bipolar subjects only, scores on the scale correlated significantly with
      number of relevant medications (r = .45, p < .05, one-tailed), with number of
      hospitalizations (r = .46, p < .05), and with psychiatrist-rated severity of
      illness (r = .45, p < .05). Bipolar patients also scored significantly higher
      than did unipolar patients on the Manic Experience subscale. The Manic
      Depressiveness Scale thus appears to have some predictive validity.

PMID- 9775664
TI  - Validity of the Perceived Criticism Measure in an undergraduate sample.
AB  - The concurrent and predictive validity of the Perceived Criticism Measure's
      Criticism and Upset subscales was assessed for undergraduates, 21 men and 98
      women. Participants were asked to identify five people important to them at
      present (typically these were parents as well as peers) and, for each, to rate
      how critical that person was as well as how upsetting they found that criticism
      to be. Scores on Upset exhibited convergent validity with another self-report
      measure of general sensitivity to criticism, whereas those on Criticism did not.
      Neither measure predicted higher ratings of criticism in a specific interaction
      with a mildly critical peer. Divergent validity with scores on a measure of
      depression was supported for Upset but was less clear for Criticism. Strong
      evidence of predictive validity for Criticism and Upset was obtained. Ratings for
      both Peer scales predicted increased negative affect after mild criticism from a
      peer, although this interaction took place 4 to 10 weeks after administration of
      the Perceived Criticism Measure.

PMID- 9775665
TI  - Correlates of primary and secondary murder.
AB  - The social correlates of the murder rates of American states in 1980 varied with
      the relationship of the victim to the murderer.

PMID- 9775666
TI  - Family capital and Hong Kong adolescents' academic achievement.
AB  - This study examined relationships between the economic, human, social, and
      cultural capital of families and adolescents' academic achievement. Data were
      collected from 387 14-yr.-old Hong Kong students (187 girls, 200 boys), who
      completed questionnaires to assess their perceptions of the various dimensions of
      family capital. Academic achievement was measured by performance in Chinese
      language, English language, and mathematics. The findings indicated that
      different combinations of the dimensions of family capital combined to contribute
      to moderate amounts of variance in adolescent girls' academic performance,
      whereas social capital was the only family measure to have a meaningful and
      significant modest association with adolescent boys' academic achievement.

PMID- 9775668
TI  - Cultural competence in three human service agencies.
AB  - This paper summarizes findings from applications of the Agency Cultural
      Competence Checklist in three human service agencies. This checklist was
      developed on the basis of published literature and culture-specific agencies were
      chosen to document checklist findings in settings known to be culturally
      competent. As anticipated, all three agencies were culturally competent in
      attitudes, although the range of services differed. This paper provides some
      baseline data for using the checklist in mainstream agencies in which
      predominantly Euro-American providers serve minority populations.

PMID- 9775667
TI  - Suicide and the shame of exposure.
AB  - A recent spate of suicides among those investigated by a Royal Commission in
      Australia on police corruption leads to the recommendation of mental health
      resources being provided for such investigations.

PMID- 9775670
TI  - Caring for terminally ill persons: comparative analysis of attitudes
      (thanatophobia) of practicing physicians, student nurses, and medical students.
AB  - To investigate why some caregivers desire to avoid patients with terminal
      illnesses, a thanatophobia scale assessing caregivers' uncomfortable feelings and
      sense of helplessness was developed and evaluated among practicing physicians and
      student nurses and medical students. As a group, student nurses scored lower on
      the thanatophobia scale than practicing physicians and medical students. Higher
      scores on intolerance to clinical uncertainty were associated with higher
      thanatophobia scores in all groups. Scores for depressed mood, decreased
      sensitivity, and Machiavellianism were statistically significant predictors in
      some groups. Higher thanatophobia scores also predicted lower scores for ratings
      of self-esteem in caring for elderly patients. Among senior medical students,
      those with lower thanatophobia scores tended to enter primary care residencies.
      Health professional educators may find this scale helpful both in pinpointing
      sources of caregivers' angst and useful in counseling students in management of
      terminally ill persons.

PMID- 9775669
TI  - Use of the MMPI-A to assess personality of juvenile male delinquents who are sex
      offenders and nonsex offenders.
AB  - The present study investigated the relationship between offender type and
      personality in 21 juvenile males adjudicated for crimes of a sexual nature and 30
      juvenile males adjudicated for nonsexual offenses including Possession of
      Narcotics, Burglary, Criminal Mischief, Assault, and other crimes involving
      property. Subjects who were aged 13 to 17 years (mean age 15) and committed to
      the State of Connecticut, Long Lane School, were administered the Minnesota
      Multiphasic Personality Inventory-Adolescent (MMPI-A). Scores on Psychopathic
      Deviate and Schizophrenia scales contributed most to the juveniles being
      classified as sex offenders, whereas scores on Hysteria and Psychasthenia
      contributed primarily to subjects being classified as nonsex offenders. A single
      discriminant function attained statistical significance, thereby correctly
      classifying 77% of the nonsex offenders and 71% of the sex offenders. Results
      indicate that sex offenders may be distinguished from nonsex offenders according
      to clinical scales of the MMPI-A.

PMID- 9775671
TI  - Socioeconomic changes associated with medical indices in the Democratic Republic
      of Croatia.
AB  - In Croatia after the demise of socialism, unemployment and poverty have risen
      dramatically. Associated health problems have increased in prevalence. Examples
      are mortality from cardiovascular disease and use of illicit drugs. At the same
      time, the number of live births and abortions have significantly decreased. The
      extreme and protracted stress reactions are associated as triggers of great
      health problems.

PMID- 9775672
TI  - Clinical trainees' recollections of their training in a diagnostic preschool
      program: a pilot study.
AB  - 26 clinician trainees' recollections of experiences in a diagnostic preschool
      program were analyzed in terms of strength and weaknesses of the program.

PMID- 9775673
TI  - A potential moderating role of stress in the association of disease activity and
      psychological status among patients with rheumatoid arthritis.
AB  - This study investigated the role of perceived daily stress as a potential
      moderator in the relation between a set of predictors (disease activity,
      education, pain) and psychological status (anxiety, depression) of 31 patients
      with rheumatoid arthritis. Psychological measures served as dependent variables
      in hierarchical regression analyses testing for potential interaction effects of
      daily stress upon relationships between predictors and dependent measures. No
      predictors predicted directly scores on depression and anxiety; however, daily
      stress directly predicted scores on depression and anxiety, even after having
      separately controlled for each of the predictors. Increased disease activity had
      significantly stronger associations with increased psychological morbidity only
      among patients reporting high scores on daily stress, suggesting a potential
      moderating role for stress.

PMID- 9775674
TI  - Predicting cirrhosis death rates in Hungary and the USA.
AB  - Marriage and birth rates predicted the rates of death from cirrhosis of the liver
      in the states of the U.S.A., but not in Hungarian counties.

PMID- 9775675
TI  - Attributional style, depression, and grade point averages of college students.
AB  - 91 upper-level undergraduates completed the Attributional Style Questionnaire and
      the Center for Epidemiologic Studies Depression Scale; scores on these
      inventories were correlated with students' cumulative grade point averages.
      Students with pessimistic attributional style scores had higher depression scores
      than students with optimistic attributional style scores and those with higher
      depression scores had lower grade point averages. The need for longitudinal
      evaluation of changes in these associations is discussed.

PMID- 9775676
TI  - Relationship between the Maternal Social Support Index and the Parenting Stress
      Index in mothers of very-low-birthweight children now age 7.
AB  - Two measures, the Maternal Social Support Index and the Parenting Stress Index
      were used to assess parents' stress and social support among mothers of 7-yr-old
      children born at very low birthweight. The MSSI Total scores did not
      significantly correlate with the PSI Total Child, Total Parent, or Total Stress
      Indices, although they were significant, but modestly correlated with scores on
      the Parent subscale of Social Isolation. The relationship between parental stress
      and maternal social support requires continued investigation.

PMID- 9775677
TI  - Predictors of outcome in drug treatment of adolescent inpatients.
AB  - Little is known about for whom treatment is most effective and how to match
      adolescent clients to substance-abuse treatment. 280 adolescents treated in a
      multifaceted program participated. Of these, 128 did not complete treatment prior
      to termination of the 2-mo. inpatient phase. They were significantly different
      from clients who completed treatment measures of alienation, social
      maladaptation, aggression, and lower occupational status of the father. Of those
      who completed inpatient treatment and remained in the study at 1-mo.
      postdischarge (n = 69) two groups were formed, those who improved and those who
      either remained the same or worsened in terms of substance abuse. For those who
      improved factors which differentiated them were identification with middle-class
      values, tendency to be older, initial difficulty identifying emotions, and
      depressive symptoms at intake. Clients who did not change or worsened were
      distinguished by more social anxiety, depressive symptoms, and troubling thoughts
      at intake. These results suggest that individual characteristics may identify
      cases who are more likely to benefit from treatment.

PMID- 9775678
TI  - Cognitive-behavioral therapy for paruresis: a case report.
AB  - This article reviews directive interventions for paruresis, the inability to
      urinate in the proximity of others. As in treatments for other anxiety disorders,
      historical interventions have included the use of paradoxical intention and
      several different forms of exposure. The results of pharmacological treatment
      have not proven promising. Although a multidimensional treatment model has been
      recommended, little attention has been paid to treating cognitive components of
      the problem. In this paper, a single case is described in which cognitive
      components of the problem of paruresis were evident. A cognitive approach and
      exposure in vivo were applied. Measures of successful trials were obtained over
      18 weeks. The combination of cognitive interventions and gradual exposure was
      effective in reducing paruresis. At follow-up 6 mo. later results had been
      maintained. The results of this case suggest more attention to the cognitive
      components is appropriate in the treatment of paruresis, as was stated previously
      for other specific social phobias.

PMID- 9775679
TI  - Subjective well-being, suicide, and homicide.
AB  - In a sample of 46 nations, suicide and homicide rates were not associated with a
      measure of subjective well-being but rather with economic indices.

PMID- 9775680
TI  - Medical students' personal values and their career choices a quarter-century
      later.
AB  - A longitudinal study of 391 physicians tested two hypotheses regarding personal
      values and career choices: that higher preference for social values would be
      associated with physicians' being more interested in "people-oriented" rather
      than "technology-oriented" specialties and that higher preference for economic
      values would be associated with expectations of high income. The physicians (344
      men, 47 women) were graduates of Jefferson Medical College in 1974 and 1975 who
      completed the Allport-Vernon-Lindzey Study of Values during medical school.
      Analysis showed that physicians currently in the "people-oriented" specialties
      scored significantly higher on the Social Value scale than their peers in
      "technology-oriented" specialties. A moderate but statistically significant
      correlation was found between scores on the Economic Value scale and expectations
      of higher income. The findings suggest that physicians' personal values are
      relevant to their career decisions such as specialty choice and expectations of
      income. The findings have implications with regard to two major issues in the
      evolving health care system, namely, the distribution of physicians by specialty
      and cost containment.

PMID- 9775681
TI  - Acculturative stress, depression, and suicidal ideation among Mexican-American
      adolescents: implications for the development of suicide prevention programs in
      schools.
AB  - The present study explored the relationship of scores on acculturative stress
      with those on depression and suicidal ideation among 26 male and 28 female
      Mexican-American students from a southern California high school. Subjects
      completed the SAFE acculturative stress scale, the Reynolds Adolescent Depression
      Scale, and the Suicidal Ideation Questionnaire-Junior. Analyses suggested that
      acculturating Mexican-American adolescents who report high scores on
      acculturative stress may report elevated scores for depression and suicidal
      ideation. Researchers should assess suicide risk within this and other
      acculturating groups, and risk factors specific to acculturating groups should be
      considered in the development and implementation of suicide prevention programs
      in schools.

PMID- 9775682
TI  - Family relations and psychosocial risk in families with an obese adolescent.
AB  - The aim of the present study is a comparison of family relations in families with
      an obese adolescent and families with a normal-weight adolescent. Particularly,
      we studied the parents' and children's perceptions of some crucial areas of their
      relationship, e.g., communication, support, and some factors of "psychosocial
      risk" for the adolescents. We compared 30 family triads each with an obese child
      and 30 family triads each with a normal-weight child. We used a questionnaire
      aimed to evaluate some crucial variables of family functioning such as
      communication, family climate, support and satisfaction. A multivariate analysis
      of variance yielded no difference between obese and nonobese adolescents
      concerning communication with their mothers and fathers and concerning support
      given and received from them. In particular, analysis indicated no difference
      between parents of obese adolescents and parents of normal-weight adolescents
      regarding openness and problems in communication. As a protective factor against
      psychosocial risk, in both the samples the relationship with the mother arises as
      relevant, but, for the nonobese adolescents, both support and communication with
      this parent were important, whereas for the obese adolescents only support seemed
      to be really important. The results are discussed with respect to this approach
      which considered the family as the unit of analysis both from a theoretical and a
      methodological point of view.

PMID- 9775683
TI  - Involvement of alcohol in murder suicides.
AB  - The blood alcohol levels present post mortem for all murder-suicides identified
      via the Queensland Suicide Register were compared with those of a sample of
      suicides matched on age, sex and method. No differences in the levels of alcohol
      were found.

PMID- 9775684
TI  - Problems with managed mental health care for multicultural populations.
AB  - Managed mental health care has developed a system of care-giving that does not
      recognize that acceptable and effective services must acknowledge individual
      differences and cultural or racial identities. This approach is unacceptable in
      an era when a psychology of differences is necessary to provide services for
      nearly one-third of the population. This paper suggests that the adequacy of
      contemporary psychoparmacological and psychological interventions for
      multicultural populations is either unknown or unsatisfactory. Historically,
      interventions in the United States were designed primarily for Euro-Americans and
      thus were culture-specific in derivation. Managed care has reduced the
      availability and quality of these interventions for all patients and further
      limited the range of possible options. Culturally competent mental health
      services are described and related to quality of care. A societal agenda for
      implementing cultural competence is suggested.

PMID- 9775685
TI  - Effectiveness of methadone maintenance for heroin addiction.
AB  - Methadone maintenance programs have effectively reduced heroin dependency and are
      available in most countries affected by heroin addiction. Methadone, developed in
      Germany during World War II as a pain killer, does not have the euphoric effects
      of heroin and the goal of treatment is to substitute methadone for heroin use.
      Recidivism is probably a life-long risk. Methadone maintenance programs began in
      the 1960s in the United States in New York City. Once tolerance is developed, it
      may be used continually without harmful side effects. Dosage is important for
      effectiveness as are counseling, rehabilitation services, and employment support.
      Reduction in criminality and AIDS has been associated with methadone maintenance
      programs.

PMID- 9775686
TI  - Compulsiveness and impulsiveness: unidimensional or bidimensional constructs?
AB  - The correlation of scores on the Obsessive-Compulsive Scale and the Barrett
      Impulsiveness Scale for 148 men and 255 women (18-84 years) was -.07, and both
      scores decreased across age groups, but age accounted for only 3% and 1.8% of the
      variance.

PMID- 9775687
TI  - Metamotivational dominance and use of tobacco and alcohol among adolescents.
AB  - This study investigated differences in metamotivational dominance among
      adolescents who engaged in different amounts of substance use, specifically,
      whether students who labeled themselves as 'heavy' alcohol consumers or cigarette
      smokers would be more Paratelic and Negativism Dominant than those who labeled
      themselves 'nondrinkers' or 'nonsmokers'. 93 secondary school students (Years 9
      and 10) participated in the study (68 boys, 25 girls). One-way analyses of
      variance indicated self-labeled heavy drinkers scored significantly more
      Paratelic Dominant than nondrinkers, while heavy smokers scored significantly
      more Paratelic and Negativism Dominant than nonsmokers. Paratelic Dominant
      adolescents who reported engaging in heavy smoking may have done so because
      smoking is defined by society as a risky behaviour and so provides arousal.
      Education and preventive programs that focus on health hazards of smoking may, in
      fact, increase the likelihood of this behaviour by both individuals who score
      Paratelic and Negativism Dominant.

PMID- 9775688
TI  - Self-reported smoking and measurement of expired air carbon monoxide in a
      clinical treatment.
AB  - In this study was evaluated the relationship between self-reported smoking rate
      and expired air carbon monoxide in 208 smokers who had attended a behavioral
      program for smoking cessation. A close relationship between carbon monoxide
      levels and self-reports was found at the end of treatment and in all follow-ups
      (6 and 12 mo.), around 100% concordance. Thus, support was found for the use of
      an expired air carbon monoxide measure as a valid and easy way of corroborating
      self-report data when required.

PMID- 9775689
TI  - Gender and marital satisfaction: data from the National Survey of Families and
      Households.
AB  - In 1972, Bernard argued that marriage was good for men and bad for women.
      Subsequent research noted that wives, on average, reported lower marital
      satisfaction than husbands. Furthermore, when differences within couples existed
      on marital satisfaction, the wife was usually the less satisfied spouse; however,
      most previous studies of the gender/marital satisfaction relationship had not
      been based on nationally representative samples. A nationally representative
      sample from the 1988 Survey of Families and Households was used to assess the
      relationship of gender with marital satisfaction. Within-couple analyses
      indicated that wives were less satisfied with their marriages than husbands and
      that, when substantial within-couple differences occurred with respect to marital
      satisfaction, the wife was usually the less satisfied spouse. Results provide at
      least small support for feminist assertions about the relatively adverse nature
      of marriage for women in the United States.

PMID- 9775690
TI  - Posttraumatic stress symptoms and depression in mothers of children with severe
      burn injuries.
AB  - This study examined posttraumatic stress symptoms and depressive symptoms in
      mothers of children with burn injuries from accidentally falling into a bathtub
      filled with hot water. Subjects were 16 pairs, children with burn injuries and
      their mothers. Psychiatric interviews were administered to the mothers to check
      the presence or absence of mental disorders. The severity of mothers' depressive
      symptoms was rated on the Hamilton Depression Scale. Prevalence rates of DSM-IV
      posttraumatic stress disorder and major depression were 6.3% and 0% in children
      with burn injury and 12.5% and 18.8% in their mothers, respectively. For three
      symptoms of posttraumatic stress disorder (intense distress at similar event,
      restricted range of affect, and hypervigilance), prevalence rates were
      significantly higher for the mothers than for the children. Ratings of the three
      symptoms of posttraumatic stress disorder for the mothers were significantly and
      positively correlated with scores for guilt feelings. Compared with children with
      burn injury, mothers are prone to posttraumatic stress symptoms mixed with guilt
      feelings for children with burn injury.

PMID- 9775691
TI  - Locus of control, sex, and attitudes toward suicide.
AB  - A sample of 191 college students were administered the Suicide Opinion
      Questionnaire and the Rotter Locus of Control Scale. Significant differences in
      endorsement were obtained on 2 of the 8 Suicide Opinion Questionnaire scales with
      respect to sex and locus of control.

PMID- 9775692
TI  - Femininity, bulimia, and distress in college women.
AB  - This study investigated differences in the scores on perceived Distress and
      Bulimia among college women with varying scores on the Behavioral Self-report of
      Femininity. Distress was assessed using The Psychological Distress Inventory and
      Bulimia was measured using the Bulimia Cognitive Distortions Scale. Women who
      reported low numbers of stereotypic feminine behaviors scored lower on the
      Bulimia Cognitive Distortions Scale than women reporting moderate to high numbers
      of stereotypic feminine behaviors. Distress scores were not significantly
      different between women scoring high and low on Bulimic Cognitive Distortions,
      and Bulimic Cognitive Distortion scores did not vary as a function of scores on
      Distress and Femininity. A multiple regression indicated that one factor of the
      Behavioral Self-report of Femininity, Social Connectedness, made a significant
      contribution to the prediction of Bulimia scores.

PMID- 9775693
TI  - Scores on a statistics test and scores on the Defense Style Questionnaire.
AB  - Scores for 21 men and 41 women on a university statistics test were compared with
      scores on the 1993 Defense Style Questionnaire of Andrews, et al. The significant
      negative association between higher scores on the statistics test and higher
      scores on the measure of the defence mechanism of projection suggested the latter
      construct be considered when examining statistical achievement.

PMID- 9775694
TI  - Measures of mental health and a five factor theory of personality.
AB  - Principal components analyses were calculated with intercorrelations of scores on
      scales measuring mental health and the five-factor model of personality on a
      sample of 296 university students. Mental health was measured with Affect Balance
      scale, Happiness Measure, Satisfaction with Life scale, Life Orientation test,
      Short Index of Self-actualization, Social Interest scale, and the Self-control
      Schedule, along with subscales from Scales of Psychological Well-being, Openness
      to Experience scale, and the Perceived Self Questionnaire. The five-factor model
      was measured with the Interpersonal Adjective Scale Revised-B5. Separate analyses
      for both the traditional five-factor model and the expanded interpersonal
      circumplex model of personality gave six-factor solutions. Scores on scales
      measuring subjective well-being, openness, and social interest loaded on the same
      factors as Neuroticism, Openness to Experience, and Agreeableness, respectively.
      Scales that measured autonomy and self-actualization formed a factor that was
      separate from the five-factor model.

PMID- 9775695
TI  - Legal gambling and crime.
AB  - In the 48 contiguous continental states in 1990, the total number of gambling
      activities was associated with robbery and motor vehicle theft rates. Controls
      for other social variables eliminated these associations.

PMID- 9775696
TI  - Alexithymia and somatic amplification in chronic pain.
AB  - A controlled study was undertaken to assess alexithymia and somatic amplification
      among 50 medical outpatients with chronic pain referred for psychiatric
      consultation. Data were collected on demographics; DSM-IV diagnoses; and measures
      of anxiety, depression, and alexithymia, assessed with the Toronto Alexithymia
      Scale (TAS-20), as well as somatic amplification, assessed with the Somatosensory
      Amplification Scale (SAS). Data analysis revealed low scores on the TAS-20 and
      SAS for the pain patients, compared with a control group without pain. In this
      sample, depression and anxiety were the primary determinants of alexithymia and
      somatic amplification, rather than pain. These findings suggest that
      psychological markers for chronic pain may be different from those for other
      somatoform disorders.

PMID- 9775697
TI  - Suicidal ideation, suicide attempts, and HIV infection.
AB  - A cross-sectional study was performed to investigate the prevalence and
      predictors of suicidal ideation and past suicide attempt in an Australian sample
      of human immunodeficiency virus (HIV)-positive and HIV-negative homosexual and
      bisexual men. Sixty-five HIV-negative and 164 HIV-positive men participated. A
      suicidal ideation score was derived from using five items selected from the Beck
      Depression Inventory and the General Health Questionnaire (28-item version).
      Lifetime and current prevalence rates of psychiatric disorder were evaluated with
      the Diagnostic Interview Schedule Version-III-R. The HIV-positive (Centers for
      Disease Control and Prevention [CDC] Stage IV) men (n = 85) had significantly
      higher total suicidal ideation scores than the asymptomatic HIV-positive men (CDC
      Stage II/III) (n = 79) and the HIV-negative men. High rates of past suicide
      attempt were detected in the HIV-negative (29%) and HIV-positive men (21%).
      Factors associated with suicidal ideation included being HIV-positive, the
      presence of current psychiatric disorder, higher neuroticism scores, external
      locus of control, and current unemployment. In the HIV-positive group analyzed
      separately, higher suicidal ideation was discriminated by the adjustment to HIV
      diagnosis (greater hopelessness and lower fighting spirit), disease factors
      (greater number of current acquired immunodeficiency syndrome [AIDS]-related
      conditions), and background variables (neuroticism). Significant predictors of a
      past attempted suicide were a positive lifetime history of psychiatric disorder
      (particularly depression diagnoses), a lifetime history of infection drug use,
      and a family history of suicide attempts. The findings indicate increased levels
      of suicidal ideation in symptomatic HIV-positive men and highlight the role that
      multiple psychosocial factors associated with suicidal ideation and attempted
      suicide play in this population.

PMID- 9775698
TI  - Depression in Parkinson's disease. The impact of symptom overlap on prevalence.
AB  - The reported prevalence of depression concomitant with Parkinson's disease varies
      greatly in the literature, which may partly be explained by symptom overlap. To
      determine the impact of symptom overlap on the prevalence, the authors tested 100
      Parkinson's disease patients for major depression (DSM-III-R) with both a
      standard, inclusive method and a diagnostic-etiologic, exclusive method. The
      authors found that the prevalence detected with the inclusive method (23%)
      decreased when the exclusive method was used (13%), which was mainly caused by
      lower scores on the item "loss of interest." The study's findings give empirical
      support for the relevance of the new category in DSM-IV "mood disorder due to a
      general medical condition."

PMID- 9775699
TI  - Olanzapine in the treatment of delirium.
AB  - Delirium is an organic psychiatric syndrome characterized by fluctuating
      consciousness and impaired cognitive functioning. Eleven delirious patients were
      treated with olanzapine (dosage mean +/- standard deviation [SD]: 8.2 +/- 3.4 mg
      qhs), and 11 delirious control patients were treated with haloperidol (dosage
      mean +/- SD: 5.1 +/- 3.5 mg qhs). Peak response time was similar in both groups.
      Five of the 11 olanzapine patients showed significant improvement (> 50% score
      reduction) on the Delirium Rating Scale (DRS) and no patients had side effects,
      whereas 6 of the 11 control subjects showed improvement on the DRS and 5 had
      extrapyramidal symptoms or excessive sedation. Olanzapine may be a useful
      alternative to haloperidol in the treatment of delirium in hospitalized patients.

PMID- 9775700
TI  - Clinical predictors of mental disorders among medical outpatients. Validation of
      the "S4" model.
AB  - The authors previously reported four clinical cues that predicted a subgroup of
      ambulatory patients likely to have depressive and anxiety disorders. The authors'
      purpose in this study was to validate this model in another cohort of 185
      consecutive adult referrals to a rheumatology clinic. The authors found 4
      variables important in predicting mental disorders: recent stress (odds ratio
      [OR]: 3.3, 95% confidence interval [CI]: 1.5-7.1); > 5 somatic symptoms (OR: 4.5,
      95% CI: 1.1-9.5); only fair or poor health status (OR: 3.4, 95% CI: 1.6-7.4); and
      symptom severity (OR: 1.6, 95% CI: 0.8-3.6). There was a stepwise increase in the
      likelihood of a mental disorder with an increasing number of predictors. The
      authors conclude that these clinical cues may allow clinicians to select patients
      in which formal screening for mental disorders would be particularly fruitful.

PMID- 9775701
TI  - Quality of life and pain in patients with recurrent breast and gynecologic
      cancer.
AB  - Pain is a central factor affecting quality of life for the cancer patient. This
      descriptive study was designed to explore the relationship between pain and
      several factors affecting quality of life. The factors explored included physical
      and social functioning, emotional health, and spiritual commitment in women with
      recurrent breast or gynecologic cancer. Pain frequency, amount, and interference
      with activities were found to correlate more strongly with objective measures of
      quality of life (i.e., physical and social functioning) than subjective measures
      (i.e., psychological or spiritual dimensions).

PMID- 9775702
TI  - Recurrent psychotic depression associated with GM2 gangliosidosis.

PMID- 9775703
TI  - Malingered dementia associated with battered women's syndrome.

PMID- 9775704
TI  - Atrial myxoma with psychiatric presentation.

PMID- 9775705
TI  - Catatonia. Another neuropsychiatric presentation of vitamin B12 deficiency?

PMID- 9775706
TI  - Interferon treatment of hepatitis C associated with symptoms of PTSD.

PMID- 9775707
TI  - Adult pica. A clinical nexus of physiology and psychodynamics.

PMID- 9775708
TI  - A schizophrenic patient's attempt to resume dialysis following renal
      transplantation.

PMID- 9775709
TI  - Cognitive-behavioral treatment of panic disorder with agoraphobia triggered by
      AICD implant activity.

PMID- 9775710
TI  - Postictal violence and epilepsy.

PMID- 9775711
TI  - Depression in corticobasal degeneration.

PMID- 9775712
TI  - Use of herbal medicines among C-L populations.

PMID- 9775713
TI  - The 3rd Abraham Conference on Preventive Nutrition: Dietary Assessment in
      Populations. Beer Sheva, Israel. 7-9 July 1997.

PMID- 9775714
TI  - Nutrition and chronic disease.

PMID- 9775715
TI  - Biomarkers in the study of diet and disease.

PMID- 9775716
TI  - The population of Israel: implications for dietary assessment.

PMID- 9775717
TI  - Dietary assessment in Israel: past experience.

PMID- 9775718
TI  - Differences between Israeli Jews and Arabs in morbidity and mortality rates for
      diseases potentially associated with dietary risk factors.
AB  - BACKGROUND: Cancer, ischemic heart disease, cerebrovascular disease and diabetes
      together comprise almost 70% of the causes of death in Israel. Dietary factors
      such as total caloric intake, saturated fats, polyunsaturated fatty acids, trace
      elements, vitamins, certain proteins, and fiber have all been suggested as
      playing a role in the pathogenesis of these diseases. AIM: In this study,
      patterns of mortality and morbidity (where available) for selected diseases were
      compared between the Jewish and Arab population groups in Israel. METHODS: Data
      on cause-specific mortality in Israel between 1973 and 1994 were obtained from
      the Israel Central Bureau of Statistics. Age-adjusted rates for selected diseases
      were compared between the Jewish and Arab population groups. RESULTS: Until 1987,
      the age-adjusted ischemic heart disease mortality rates in the Arab population
      were slightly lower than those in the Jewish population. Since 1990, they have
      been slightly higher. Cerebrovascular disease mortality rates have consistently
      been higher in the Arab population and the gap has been increasing. Similarly,
      the mortality rates for diabetes mellitus were slightly higher in the Arab
      population during the 1970 and 1980s and the gap has increased markedly. On the
      other hand, age-adjusted mortality rates from colorectal cancer are about three
      times as high and breast cancer mortality rates about twice as high in the Jewish
      population. The differences for incidence rates are even greater. CONCLUSIONS:
      This study demonstrates the contradictory mortality rates for cardiovascular
      disease as compared with colon and breast cancer in the Jewish and Arab
      population. While representative dietary data for the populations are lacking,
      there is evidence that the dietary patterns of the Jewish and Arab population
      groups differ in many important aspects. It is possible that this may at least
      partly explain the contradictory differences in mortality and morbidity. The
      national nutrition surveys currently being initiated by the Ministry of Health
      should contribute to a better understanding of this subject.

PMID- 9775719
TI  - Development and maintenance of nutrient databases for nutritional epidemiological
      studies.

PMID- 9775720
TI  - Development and maintenance of nutrient databases for national dietary surveys.

PMID- 9775721
TI  - Nutrient database development and management: an NHANES perspective.

PMID- 9775722
TI  - Experiences with dietary assessment in the Middle East.

PMID- 9775723
TI  - The DAFNE food data bank as a tool for monitoring food availability in Europe.
      DAta Food NEtworking.
AB  - DAFNE, the acronym for DAta Food NEtworking, aims at the creation of a pan
      European food data bank based on household budget surveys. It relies on household
      budget surveys that provide a unique source of dietary information that can be
      used to form a system that meets several requirements, including large sample
      size, representativeness, timeliness, and economic efficiency. In this brief
      overview of the project, the methodology is summarised, validation procedures are
      indicated, and examples of the information that can be harvested is provided. The
      DAFNE data could provide the background for the development of recommended
      dietary objectives customised to particular populations and form the basis for
      evidence-based nutritional policies serving guidelines of global applicability.

PMID- 9775724
TI  - Sources of nutritional data in Israel.

PMID- 9775725
TI  - Differential nutritional habits in distinct ethnic groups in the Israel
      population.

PMID- 9775726
TI  - Statistical issues in dietary assessment in surveys and etiological studies.

PMID- 9775728
TI  - Adjustment for misclassification bias in epidemiological studies of nutrition and
      disease.

PMID- 9775727
TI  - Some statistical considerations in the analysis of dietary epidemiologic studies.

PMID- 9775729
TI  - The association between daily caloric intake, physical activity, and blood
      insulin.

PMID- 9775730
TI  - Nutrition policy formulation and public health implications: the Norwegian
      experience.

PMID- 9775731
TI  - Health, food, and nutrition policy.

PMID- 9775733
TI  - Development of a food and nutrition policy for Palestine.

PMID- 9775732
TI  - Uses of food consumption data: with an example exploring the impact of food
      consumption on economic growth.

PMID- 9775734
TI  - The children's vaccine initiative (CVI) and WHO's global programme for vaccines
      and immunization (GPV). Recommendations from the Scientific Advisory Group of
      Experts (SAGE). Part II.

PMID- 9775735
TI  - Power imbalance--evolving theory in need of research.

PMID- 9775736
TI  - Mentoring and nurse practitioner student self-efficacy.
AB  - The relationship between nurse practitioner students and their clinical teachers
      (preceptors) may have an impact on students' confidence in their ability to take
      on the advanced practice role of the nurse practitioner. This descriptive,
      correlational study investigated the relationship between nurse practitioner
      students' perceptions of mentoring by their clinical preceptors and student self
      efficacy. Bandura's Self-Efficacy Theory and Biddle's Role Theory provided the
      framework for the research. Study results may have an impact on graduate nursing
      program philosophy, clinical placement management strategies, and preceptor
      selection.

PMID- 9775737
TI  - Correlates of nurse practitioners' diagnostic and intervention performance for
      domestic violence.
AB  - The purposes of this research were to identify diagnosis and intervention
      performance accuracy, variables that influence this performance accuracy, and
      barriers that impede performance accuracy of adult nurse practitioners (ANP) and
      family nurse practitioners (FNP) for domestic violence. Two measures were
      developed: the Nurse Practitioner Survey (NPS) and the Nurse Practitioner
      Performance Tool. A total of 118 ANPs and FNPs completed and returned mailed
      surveys. Of these, 22 individuals were interviewed by telephone regarding
      personal and professional experience with domestic violence and barriers in their
      clinical settings to addressing domestic violence.

PMID- 9775738
TI  - Jurisdiction in community nursing services.
AB  - This article focuses on community-health nursing services and their jurisdiction
      in Norway. The aim of the study was to analyze and gain a better understanding of
      community-nursing services' jurisdiction and jurisdictional pressure. The areas
      of investigation were degree of jurisdictional control, pattern of pressure in
      the jurisdiction, and nurses' strategies to deal with this pressure. The
      respondents were nurses in public health nursing service, home nursing service,
      and nursing homes. The results showed that nurses in the three different
      community-nursing services had different degrees of formal and informal control
      in their jurisdictions. Patterns of pressure were visible both inside and outside
      of the jurisdiction. Jurisdictional pressure led to strategies that strengthened
      control of the work, fortified professional status, or both.

PMID- 9775739
TI  - Graduate student-faculty collaboration in research and publication.
AB  - The nursing profession advocates development of theoretical knowledge as a basis
      for nursing practice and promotes preparation of graduate students as nursing
      scholars. This study explored the influence of selected factors on the publishing
      efforts of student authors who published in the Western Journal of Nursing
      Research during a 5-year period. Assignments, particularly for a dissertation,
      provided a significant impetus for publishing. Self-selection of a topic of
      interest also was an important factor. Approximately one third of the student
      authors had collaborated with faculty as coauthors. Graduate students make a
      significant contribution to the creation and dissemination of nursing knowledge.
      The influence of collaboration with faculty, the defining elements of
      collaborative mentorship, and inherent ethical issues should be investigated in
      future studies.

PMID- 9775740
TI  - Expert nursing assistant care activities.
AB  - Expert nursing assistants (NAs) described a broad range of care activities
      provided for nursing home residents. Data from in-depth interviews were analyzed
      using a naturalistic inquiry approach. Functional care activities addressed
      activities of daily living. Seven types of psychosocial care activities promoted
      emotional and mental health. NAs also described activities beyond the scope of
      their training, yet delegated by licensed nurses. Identification of expert NA
      contributions to resident care, proposed as the highest level of NA care
      possible, can guide development of educational programs and evaluation
      instruments. Awareness of delegated activities can direct research regarding
      their safety and legality.

PMID- 9775741
TI  - Swedish nursing students' transition into nursing during education.
AB  - The transition from student to nurse involves the influence of several different
      educational aspects. The aim of this study is to elucidate the transition to the
      role of a nurse, which Swedish nursing students underwent during their 3 years in
      nursing education, as described from the perspective of their experiences with
      elderly patients. Interviews were conducted with the students at the end of each
      academic year, and the students wrote diaries about their clinical education in
      the second and third years. The narratives were analyzed with a phenomenological
      hermeneutic method, and six themes appeared vital for the transition into
      nursing. The study implies a continuous process during education, involving many
      aspects of the transition from a student with a genuine and natural interest to
      care for others to a registered nurse ready to take up her first position.
      Cooperation with other team members had a strong influence on the students.

PMID- 9775743
TI  - Advocate for our children--physicians working with schools make a difference.

PMID- 9775742
TI  - Measuring the intervention in effectiveness research.
AB  - Inconsistent implementation of the intervention in the field setting presents a
      threat to the validity of the conclusions of an effectiveness study. Inconsistent
      implementation results in variability in the actual dosage of the intervention
      received by the participants, which leads to variability in outcomes achievement
      and, consequently, to Type II error. This article discusses the methodological
      implications of inconsistent intervention implementation and advances a strategy
      as a solution to this problem. The strategy proposes to quantify the dosage of
      the intervention as a continuous variable and to use this variable in the
      statistical analysis. The benefits of this strategy are illustrated with an
      empirical example from the Self-Help Intervention Project.

PMID- 9775744
TI  - "2% by 2000" to prevent child neglect and abuse.

PMID- 9775745
TI  - Caring for our most valuable natural resource: school age children.

PMID- 9775746
TI  - Critical adolescent health issues: results of the 1997 Wisconsin Youth Risk
      Behavior Survey.

PMID- 9775747
TI  - Wisconsin's Comprehensive School Health Program (CSHP).

PMID- 9775748
TI  - Wisconsin's new guide to school nursing and health services.

PMID- 9775749
TI  - Health services in Madison Metro School District.

PMID- 9775750
TI  - Good breakfast for good learning.

PMID- 9775751
TI  - Wrestling the scale not the opponent.

PMID- 9775752
TI  - Tracking and improving children's health.

PMID- 9775753
TI  - What's the matter with kids today?

PMID- 9775754
TI  - Advances in the care of children with heart disease.
AB  - As we enter the next millennium, we are encouraged by the progress that has been
      made in the care of neonates, infants, and children with heart disease. Surgical
      repair can be offered at an earlier age with excellent results. Diseases that
      were uniformly fatal in the past have improved outcomes. Research continues in
      the area of interventional devices such that surgical repair might be eliminated
      or delayed. We continue to look forward to advances in the next several years
      that will allow for future improvement in outcome, better quality-of-life and
      better long-term results.

PMID- 9775755
TI  - Quality-of-life in technology-dependent children receiving home care, and their
      families--a qualitative study.
AB  - PURPOSE: This qualitative study explored quality-of-life (QL) issues among
      Wisconsin's technology-dependent children and their families. METHODS: Five semi
      structured focus groups were held with parents, siblings and health care workers
      of home-dwelling children dependent upon technology such as tracheostomy,
      ventilator support and gastrostomy tube feedings. Focus group transcripts were
      analyzed using an editing style format, with each author as an independent
      analyst. RESULTS: QL for the child was seen as a relative term, defined within
      the family, dependent upon the availability of services; and expressed in terms
      of physical comfort and function, and integration of the child into the family
      and community. Positive QL aspects for families include: growth as individuals,
      intrinsic rewards from the child and appreciation of others with handicaps.
      Negative impacts on family QL include: physical and mental anguish (e.g.,
      exhaustion, suicidal ideation, back injuries), inhibitions of normal family
      functions, and isolation. Home nursing was highly valued despite lack of privacy.
      A number of ethical issues emerged including ineffective communication and lack
      of QL discussions during the child's acute treatment, end-of-life decisions, and
      potential cuts in Medicaid services. The latter issue prompted fear of poverty
      and divorce among siblings. CONCLUSIONS: Technology appears to exceed the
      sociological and ethical components of the care of these children, and QL is
      defined in terms of physical comfort, functional status, adequate services, and
      family/community integration. Parents assume an ambiguous medical role with their
      child, and need respite care and advocacy from their health care team.

PMID- 9775757
TI  - Diabetes outpatient project.

PMID- 9775758
TI  - Pharmacists administering vaccines--an increase in your liability?

PMID- 9775756
TI  - Leukemia and kidney failure: case presentation and review of the literature.

PMID- 9775759
TI  - Pollutant transport during a regional O3-episode in the mid-Atlantic states.
AB  - Ozone (O3) concentrations in the Baltimore-Washington (B-W) metropolitan area
      frequently exceed the National Ambient Air Quality Standard (NAAQS) in the summer
      months. The most extreme O3 events occur in multi-day high O3 episodes. These
      events can be regional in scale, with O3 concentrations exceeding the NAAQS at
      numerous locations along the eastern U.S. seaboard, and are typically associated
      with slow-moving or stagnant high pressure systems. In the B-W region, the most
      extreme events typically occur with surface high pressure overhead or just west
      of the region and an upper air high-pressure area (ridge) to the west or
      northwest. Besides providing conditions conductive to local O3 production
      (subsidence and strong low-level inversions, weak horizontal winds, little cloud
      cover), this weather pattern may also result in transport of O3 and its
      precursors from heavily industrialized areas west and north of the B-W region. In
      this paper, observations and back trajectories made during the severe regional O3
      event of July 12-15, 1995, are used to confirm the hypothesis that significant
      regional-scale transport of O3 and its precursors occur during extreme O3 events
      of the standard type in the B-W area.

PMID- 9775760
TI  - A discussion of regulatory requirements and air dispersion modeling approaches
      applicable to U.S. chemical demilitarization facilities.
AB  - Owners of hazardous waste treatment, storage, and disposal facilities, and
      certain major air pollution sources, must conduct several separate ambient air
      dispersion modeling analyses before beginning construction of new facilities or
      modifying existing facilities. These analyses are critical components of the
      environmental permitting and facility certification processes and must be
      completed to the satisfaction of federal, state, and local regulatory
      authorities. The U.S. Army has conducted air dispersion modeling for its proposed
      chemical agent disposal facilities to fulfill the following environmental
      regulatory and risk management requirements: (1) Resource Conservation and
      Recovery Act human health and ecological risk assessment analysis for the
      hazardous waste treatment and storage permit applications, (2) Quantitative Risk
      Assessment to support the site-specific risk management programs, and (3)
      Prevention of Significant Deterioration ambient air impact analysis for the air
      permit applications. The purpose of these air dispersion modeling studies is to
      show that the potential impacts on human health and the environment, due to
      operation of the chemical agent disposal facilities, are acceptable. This paper
      describes and compares the types of air dispersion models, modeling input data
      requirements, modeling algorithms, and approaches used to satisfy the three
      environmental regulatory and risk management requirements listed above. Although
      this paper discusses only one industry (i.e., chemical demilitarization), the
      information it contains could help those in other industries who need to
      communicate to the public the purpose and objectives of each modeling analysis.
      It may also be useful in integrating the results of each analysis into an
      overarching summary of compliance and potential risks.

PMID- 9775761
TI  - Simultaneous sulfur dioxide and nitrogen dioxide removal by calcium hydroxide and
      calcium silicate solids.
AB  - At conditions typical of a bag filter exposed to a coal-fired flue gas that has
      been adiabatically cooled with water, calcium hydroxide and calcium silicate
      solids were exposed to a dilute, humidified gas stream of nitrogen dioxide (NO2)
      and sulfur dioxide (SO2) in a packed-bed reactor. A prior study found that NO2
      reacted readily with surface water of alkaline and non-alkaline solids to produce
      nitrate, nitrite, and nitric oxide (NO). With SO2 present in the gas stream, NO2
      also reacted with S(IV), a product of SO2 removal, on the exterior of an alkaline
      solid. The oxidation of S(IV) to S(VI) by oxygen reduced the availability of
      S(IV) and lowered removal of NO2. Subsequent acidification of the sorbent by the
      removal of NO2 and SO2 facilitated the production of NO. However, the conversion
      of nitrous acid to sulfur-nitrogen compounds reduced NO production and enhanced
      SO2 removal. A reactor model based on empirical and semi-empirical rate
      expressions predicted rates of SO2 removal, NO2 removal, and NO production by
      calcium silicate solids. Rate expressions from the reactor model were inserted
      into a second program, which predicted the removal of SO2 and NOx by a continuous
      process, such as the collection of alkaline solids in a baghouse. The continuous
      process model, depending upon inlet conditions, predicted 30-40% removal for NOx
      and 50-90% removal for SO2. These results are relevant to dry scrubbing
      technology for combined SO2 and NOx removal that first oxidizes NO to NO2 by the
      addition of methanol into the flue duct.

PMID- 9775762
TI  - Determination and parameterization of some air pollutants as a function of
      meteorological parameters in Kayseri, Turkey.
AB  - In this paper, the statistical relations between meteorological parameters and
      some pollutant ground level concentrations are presented. The daily average
      sulfur dioxide and smoke values were measured at five stations in Kayseri over 20
      months. The model adopted for analysis differed from the power-law form selected
      by former investigators. Wind speed, degree-day temperature, the percentage of
      relative humidity, the previous day's pollution concentrations, and the amount of
      global solar radiation were the variables of multiple regression equations that
      were derived to calculate pollutant concentrations. The amount of cloud cover,
      however, had no important effect on the pollutant concentrations. The average
      variances of these regression equations were found as 84 and 75% for sulfur
      dioxide and smoke concentrations, respectively. The calculated pollutant
      concentrations utilizing forecast meteorological parameters reflected that the
      occurrence of high pollutant concentrations can be predicted.

PMID- 9775763
TI  - Helping clients in their sexual expression.

PMID- 9775764
TI  - What direction for mental health research?

PMID- 9775765
TI  - Moving and handling practice in neuro-disability nursing.
AB  - This article examines the challenge of implementing a safer handling policy in an
      environment which caters for the needs of people who have complex and profound
      disability. It explores how a moving and handling educational strategy has been
      developed and the effectiveness of the strategies employed. The impact of
      changing practice at ward level and the difficulties encountered will be
      discussed in light of the patients' complex needs. The effects of the strategy
      are outlined with regard to accident reporting and the impact of legislation
      regarding moving and handling in an environment where patients' needs have to be
      balanced with staff safety are considered.

PMID- 9775766
TI  - Prostatic cancer and men's healthcare needs.

PMID- 9775767
TI  - Current feeding policies for patients with stroke.
AB  - It is well known that policies for feeding patients who have suffered a recent
      stroke vary enormously. The choice of method used may depend on the severity of
      the stroke, i.e. swallowing ability, conscious level, ability to communicate and
      the level of sensory and motor dysfunction. Other considerations may include age
      and previous nutritional status. However, in the absence of evidence from
      controlled clinical trials, the preferences of individual physicians and nurses
      may have a significant influence. As part of the preparatory work before the
      start of a clinical trial of different feeding policies, the author wished to
      assess both the degree of variability of feeding practice on wards in the same
      hospital and also whether there were reasons other than lack of evidence which
      influenced feeding policies. One nurse from each of 19 wards (one neurology, nine
      medical and nine care of the elderly) in two hospitals of the same trust was
      interviewed to ascertain their current feeding practice for patients with stroke.
      The results showed the expected variability in feeding practice, possibly
      reflecting the uncertainties felt by physicians and nurses in this area. However,
      many comments revealed the concerns that nurses have in trying to meet the
      nutritional needs of their stroke patients in busy acute general hospitals.

PMID- 9775769
TI  - Incapable adults and informal admission: another scenario.
AB  - The Court of Appeal has once again caused a flurry of consternation with its
      decision that patients incapable of giving consent to admission to psychiatric
      hospital must, if the statutory provisions are present, be admitted compulsorily
      under the Mental Health Act 1983. This article submits that this decision can
      only cause increased bureaucracy and distress for thousands of mentally
      incompetent adults. The long-term solution is for the Law Commission's proposals
      for decision making for mentally incompetent adults to be enacted.

PMID- 9775768
TI  - Incapable adults and informal admission: lifting the veil of deceit.
AB  - Since 1959, informal admission has been used for the admission of non-resisting
      adults to hospital for treatment of their mental health problems. The Court of
      Appeal has ruled this practice unlawful. As a consequence, certain issues in
      relation to the admission and management of these patients will have to be
      reconsidered and while there will be positive repercussions for the management of
      patients there will also be some negative effects. This article considers the
      implications.

PMID- 9775770
TI  - PAT: advanced nursing interventions for eating disorders.
AB  - Passive activity time (PAT) is a nursing intervention that was developed for
      young people with eating disorders. This development was a pioneering attempt to
      examine the nursing care for this client group and improve treatment programmes.
      Nursing practice before PAT was dominated by a biomedical model which directed a
      set procedure of care for all patients, focusing primarily on weight restoration.
      The prominent interventions were bed rest for any patient who was under weight
      and a strict dietary regimen. PAT was the result of a change in nursing practice
      towards a more holistic philosophy of care. This article will describe the
      rationale behind its development and discuss its potential in future nursing
      practice for people experiencing anorexia nervosa.

PMID- 9775771
TI  - Homeostasis: a framework for integrating the life sciences.
AB  - Nurse education curricula continue to emphasize the holistic nature of health and
      ill-health. As a concept, holism recognizes that the interactions between a
      person and his/her environment are significant factors in shaping the individual,
      and important determinants of wellbeing. Psychosocial interactions as a basis for
      health now figure prominently in nursing curricula. In contrast, the applied
      biological sciences have increasingly become marginalized, yet knowledge of the
      biological construct of the individual, and an understanding of how it is
      influenced by psychosocial interactions, are also necessary if holistic care is
      the aim. Nursing models attempt to reinforce holistic principles, but the
      integrative nature of health and illness needs to be established before their
      application. This article proposes that the concept of homeostasis, and its
      relationship to systems theory, provides a workable framework for teaching the
      basis of health, and so forms a foundation for the application of nursing theory
      and nursing models.

PMID- 9775772
TI  - Role of the nurse: introducing theories and concepts.
AB  - This article is a descriptive analysis of the work of nurse theorists in relation
      to the role of the nurse. It is clear from the literature that nursing is
      difficult to define but it is possible to identify the core values of nursing and
      the commonalities that run through the profession. The core components identified
      by an examination of the literature are the development of systems for the
      delivery of care, coordinating care, teaching, defending the frail and
      vulnerable, caring for the ill and the well, and providing technical care. This
      article aims to provide a baseline picture of what nursing is and how it is
      described in nursing models allowing readers to examine and compare their own
      values and image of nursing with what the theorists have written.

PMID- 9775773
TI  - 3M Cavilon No Sting Barrier Film in the protection of vulnerable skin.
AB  - Skin often becomes vulnerable in incontinent patients or following the use of
      aggressive adhesive tapes and dressings. Until recently the only products
      available for use on such skin have been ointments, creams and alcohol-based
      products. 3M Health Care has launched a range of no sting barrier film
      applicators that provide skin protection in many scenarios, but in a product that
      does not sting or cause pain on application.

PMID- 9775774
TI  - Prison services are in need of urgent reform.

PMID- 9775776
TI  - Needlestick injury: my personal story.

PMID- 9775775
TI  - Sharps injuries & preventive measures.

PMID- 9775777
TI  - Reflections of a Canadian RNFA. Past, present and future.

PMID- 9775778
TI  - Expanding the perioperative role with RNFA certification.

PMID- 9775779
TI  - Putting nursing forward. Strategies for the next millennium.

PMID- 9775780
TI  - Skill mix and clinical outcomes.

PMID- 9775781
TI  - Politics as relationships.

PMID- 9775782
TI  - Nursing's national role in health policy. Interview by Marjorie Jamieson.

PMID- 9775783
TI  - Grass roots efforts. Nurses involved in the political process.

PMID- 9775784
TI  - Nursing's ethical mandate: endorsing candidates.

PMID- 9775786
TI  - Thirty years of primary nursing.

PMID- 9775785
TI  - Boosting minority student success.

PMID- 9775787
TI  - A visible community of primary nurses. Interview by Marie Manthey.

PMID- 9775788
TI  - Primary nursing's impact on long-term care.

PMID- 9775789
TI  - A nursing assistant's view.

PMID- 9775790
TI  - The primary relationship in home care.

PMID- 9775791
TI  - A noticeable seamlessness.

PMID- 9775792
TI  - Case managing, intervening early.

PMID- 9775793
TI  - The Primary Nurse Award winner: a steadfast stance for constancy. Interview by
      Pat Jakobsen.

PMID- 9775794
TI  - Stopping the madness: emergency nurses and violence prevention.

PMID- 9775795
TI  - More on saline flush study.

PMID- 9775796
TI  - Found down: compartment syndrome, rhabdomyolysis, and renal failure.

PMID- 9775797
TI  - Beyond the basics: monitoring with a pulmonary artery (Swan-Ganz) catheter.
AB  - Interpreting hemodynamic parameters requires both knowledge and practical
      experience. As emergency nurses care for more acutely ill patients during longer
      ED stays, an understanding of hemodynamic monitoring will be essential.

PMID- 9775798
TI  - Noninvasive pacing: what you should know.
AB  - Noninvasive pacing is a valuable therapy in emergency cardiac care. The more
      experience clinicians have with the noninvasive pacing procedure, the greater
      their confidence and the easier the job becomes. Effective troubleshooting during
      pacing becomes less problematic with increased experience with the therapy.
      Noninvasive pacing allows rapid initiation of emergency pacing and "buys time" to
      stabilize the patient and plan further care.

PMID- 9775799
TI  - Role and productivity of nurse practitioners in one urban emergency department.
AB  - Data gathered from this one institution, although not necessarily generalizable,
      proved helpful in retaining the NP role in our emergency department. Other
      facilities may benefit from a similar analysis of like information.

PMID- 9775800
TI  - Dobutamine stress echocardiogram: emergency department evaluation of chest pain.

PMID- 9775801
TI  - Strokes, CVAs, or brain attacks: by any name they need quick attention.

PMID- 9775802
TI  - Summary of strategies for managing severe traumatic brain injury during the early
      posttraumatic phase.

PMID- 9775803
TI  - Scripted demonstrations: a screening tool for ED computer software system
      selection.

PMID- 9775804
TI  - Hospital-wide domestic violence education.

PMID- 9775805
TI  - Buckle up for Nik.

PMID- 9775807
TI  - SANE expert and factual testimony.

PMID- 9775806
TI  - Ethical issues in publication of research.
AB  - We often think of research ethics mostly in connection with the processes of
      intervention, data collection, and analysis, but ethics does not stop there. The
      process of preparing publications involves a number of ethical considerations,
      including continued protection of the rights of human subjects; reporting
      findings truthfully, accurately, and completely and using one's own words to do
      so, or appropriately citing the work of others; and ensuring that authorship
      credit and acknowledgments accurately reflect the contributions of others. No
      foolproof way exists to ensure that only ethical publications see print; however,
      including content on publication ethics in all research courses, publishing clear
      policies related to ethical expectations in journals, and engaging in discussion
      of these issues with colleagues are a good start toward that goal.

PMID- 9775808
TI  - Flail chest: a nursing challenge.
AB  - Caring for a patient with a flail chest poses a significant challenge to the ED
      nurse. Performing serial evaluation, complicated pain management, and diligent
      pulmonary toilet will put your nursing skills to the test! Finding the time to do
      it in a busy emergency department ... well, that's a topic for another article.

PMID- 9775809
TI  - A 62-year-old woman with periorbital swelling.

PMID- 9775810
TI  - Renaissance nurse: Debby Henderson, lecturer, writer, teacher, mentor, patient
      advocate, nursing advocate. Interview by Marlene Jezierski.

PMID- 9775811
TI  - The nurse was there.

PMID- 9775812
TI  - Advocacy--an integral part of emergency nursing.

PMID- 9775813
TI  - On leadership and learning.

PMID- 9775814
TI  - "Tyson squats" as a cause of rhabdomyolysis.

PMID- 9775815
TI  - Research article on "efficacy of normal saline solution vs. heparin solution"
      applauded.

PMID- 9775816
TI  - Expect the unexpected.

PMID- 9775817
TI  - Scombroid fish poisoning.

PMID- 9775818
TI  - Blood transfusion error (barely) avoided.

PMID- 9775819
TI  - A 30-year-old pregnant woman with pulmonary edema from a clotted mechanical
      aortic valve.

PMID- 9775820
TI  - Home care referral after emergency department discharge.
AB  - OBJECTIVE: The purpose of this study was to assess the need for home health care
      referral screening for elderly patients after ED discharge. The specific research
      question addressed was: Is there a need for home care referral screenings for
      elderly patients discharged from the emergency department? DESIGN: A
      nonexperimental, retrospective, descriptive design was used in this project.
      METHODS: A convenience sample of 194 closed medical records was obtained from a
      Midwestern hospital emergency department. The medical records were from patients
      65 years of age and older who had visited the emergency department during a 3
      month period. One chart audit tool was completed for each medical record.
      RESULTS: Eighty-eight (45.4%) of the 194 patients in the study could have
      benefited from a home care referral. CONCLUSION: Elderly patients frequently
      access the health care delivery system through the emergency department, but
      little is known about the outcomes of such usage, particularly in the context of
      continuity of care. If home care referral screenings of elderly ED patients are
      performed and appropriate referrals are made before ED discharge, a seamless
      delivery system of health care is provided. A home care visit resulting from a
      referral may be all that is needed for the maintenance of a patient's condition.
      To improve the quality and continuity of patient care, home care screening should
      be integrated into the routine discharge ED activities.

PMID- 9775822
TI  - Childhood submersion injuries.
AB  - The overall prognosis for children who sustain a submersion incident is directly
      related to several variables including length of submersion, initial neurologic
      evaluation, time to first breath, initial pH, and others. Resuscitation after
      near-drowning is unsuccessful in terms of death and neurologic deficit in 30% of
      those children who are treated at our institution. Despite the fact that we have
      been able to present variables that are somewhat predictive of outcome, it is
      almost impossible to identify 100% of the time which particular comatose child
      will survive neurologically intact. Therefore skilled attempts at resuscitation
      and management are mandatory. The understanding of the sequence of events that
      occur during the drowning process and the pathophysiologic consequence make it
      possible for health care personnel to provide aggressive therapeutic
      interventions that will enhance the likelihood of a normal recovery.

PMID- 9775821
TI  - Perceptions, safety behaviors, and learning needs of parents of children brought
      to an emergency department.
AB  - INTRODUCTION: This study was conducted at a level II Pediatric Trauma Center to
      assess the perceptions, safety behaviors, and learning needs of parents who
      brought their children to the emergency department. METHODS: Surveys were
      distributed in the emergency department, and 412 parents/caretakers responded. A
      descriptive design provided the framework for data analysis. RESULTS: A profile
      of caretakers of children in three age groups (1 to 4, 5 to 12, and 13 to 15
      years) emerged. Whereas most parents and older children knew how to call 911,
      only half of the parents knew child CPR. Parents tended to underestimate their
      children's risks for motor vehicle-related and immersion injuries and were more
      concerned about kidnapping and assault. Less than half of the parents believed
      that most injuries can be prevented. Learning needs were indicated by 34% of
      parents, and CPR was mentioned most frequently. Parents' desires for learning
      tended to focus on care after injuries happened. DISCUSSION: Health professionals
      need to spend more time teaching parents about the link between child development
      and risks for injury, to emphasize prevention. Interventions based on study
      results include the hospital Safety Helmet Discharge Plan.

PMID- 9775823
TI  - The latex allergy triage or admission tool: an algorithm to identify which
      patients would benefit from "latex safe" precautions.

PMID- 9775824
TI  - A sign of the times: THINK signs at sites of alcohol-related fatalities.

PMID- 9775825
TI  - How one ED manager stays organized with a one-page form.

PMID- 9775826
TI  - Radiologic assessment of the injured elbow.

PMID- 9775827
TI  - Nursing care for diabetic patients with alcohol-induced hypoglycemia.
AB  - The combination of diabetes and alcohol poses a potentially serious threat for 16
      million persons in the United States. With the prevalence of diabetes increasing,
      health care providers working in acute care settings need to be prepared to
      recognize alcohol-induced hypoglycemia quickly and respond with appropriate
      treatment. Prompt recognition of the problem and rapid implementation of
      appropriate therapies may help decrease the current cost of diabetes for the
      nation, which exceeds $100 billion a year, and also contribute toward the U.S.
      Department of Health and Human Services Healthy People 2000 goal of decreasing
      diabetes-related deaths and complications.

PMID- 9775828
TI  - Establishing a forensic nurse council within a state nurses association: the
      Tennessee Nurses Association Council of Forensic Nurses.

PMID- 9775829
TI  - Reference checks: a tool of system selection.

PMID- 9775830
TI  - A triage vital sign policy for a children's hospital emergency department.

PMID- 9775831
TI  - Ethical issues in industry-sponsored research.

PMID- 9775832
TI  - SANE development and operation guide.

PMID- 9775833
TI  - A 55-year-old patient with chronic lung disease and intractable shortness of
      breath.

PMID- 9775834
TI  - Standing beside you.

PMID- 9775835
TI  - Emergency Nurses Association position statement. Latex allergy.

PMID- 9775836
TI  - Breastfeeding and the bottom line: why are the cost savings of breastfeeding such
      a hard sell?

PMID- 9775837
TI  - Growth patterns of breastfed infants and the current status of growth charts for
      infants.
AB  - In summary, numerous studies have indicated that the pattern of growth during
      infancy is influenced by feeding mode. Compared to formula-fed infants, breastfed
      infants generally gain less weight, particularly after the first few months of
      life. This appears to be a normal pattern among healthy, thriving infants.
      Although true growth faltering can certainly occur among breastfed infants, it is
      difficult to evaluate using the NCHS growth chart, which is based on a sample of
      predominantly formula-fed infants. This situation has prompted WHO to begin the
      process of creating a new growth chart based on breastfed infants.

PMID- 9775838
TI  - The influence of breastfeeding on the development of the oral cavity: a
      commentary.

PMID- 9775839
TI  - Fortified human milk.

PMID- 9775840
TI  - Human milk fortifiers are not "nature's way".

PMID- 9775841
TI  - Contamination in expressed breast milk.

PMID- 9775842
TI  - Risk factors for lactation mastitis.
AB  - The research undertaken in this study utilized a case-control group nested within
      a prospective cohort which was followed for the first 3 months postpartum.
      Mothers with mastitis and their controls were requested to complete a self-report
      questionnaire designed to investigate the association between the potential risk
      factors, identified from the literature, and lactation mastitis. Logistic
      regression analyses of the possible risk factors were performed separately for
      mothers who had not breastfed previously and those mothers who had breastfed at
      least one infant prior to this lactation. Analysis showed blocked duct(s) and
      increased levels of stress were the significant predictors for mastitis in
      mothers who had breastfed a previous infant and blocked duct(s), restriction from
      a tight bra, attachment difficulties, and nipple pain during a feed were the
      significant predictors for mastitis in first time breastfeeding mothers.

PMID- 9775844
TI  - Body weight, body composition, and energy intake changes in breastfeeding
      mothers.
AB  - Body weight, body composition, and energy intake changes are described for 13
      breastfeeding mothers followed for 18-24 months after delivery. Body weight was
      assessed at 1-6, 9, 12, 18, 24 months postpartum and 1 month after infant
      weaning, and energy intake was assessed at 2-6, 9, 12, 18, 24 months postpartum
      and 1 month after infant weaning. Compared to prepregnancy weight, participants
      were an average of 4.0 +/- 6.6 kg heavier 18 months postpartum (p < 0.05). The
      mean rate of weight loss from 1 month postpartum until termination of lactation
      was 0.32 +/- 0.27 kg/month. Eight of the 12 women gained weight after weaning
      their infant. Percent body fat assessed by underwater weighing declined from 34.6
      +/- 2.8% at 1 month postpartum to 31.4 +/- 4.8% at 1 month after infant weaning
      (p < 0.05). Further research is needed to study the factors which affect weight
      loss postpartum, and how weight gain after weaning can be prevented.

PMID- 9775843
TI  - The effects of calcium supplementation, duration of lactation, and time of day on
      concentrations of parathyroid hormone-related protein in human milk: a pilot
      study.
AB  - This pilot study reports parathyroid hormone-related protein (PTHrP) in milk from
      14 women (placebo = 6, calcium = 8) over the duration of lactation. Milk samples
      collected 0 to 250 days postpartum were assayed for PTHrP by a two-site
      immunoradiometric assay. PTHrP concentrations were significantly lower in
      colostrum 0-4 days postpartum (5,080 +/- 1575 pmol/L) than at 7-60 days
      postpartum (11,863 +/- 1528-14,213 +/- 1574 pmol/L); concentrations did not
      differ between calcium and placebo groups. A suggestive diurnal variation was
      seen in two women who collected milk samples over 48 continuous hours.
      Confounding factors related to milk synthesis and milk sampling contribute to
      variability in PTHrP concentrations.

PMID- 9775845
TI  - Breastfeeding and the sexual abuse survivor.
AB  - In this paper, the possible effects of child sexual abuse on a mother's
      breastfeeding experience are described. The long-term effects of sexual abuse are
      divided into seven domains that may impact breastfeeding behavior: posttraumatic
      stress disorder, cognitive distortions, emotional distress, impaired sense of
      self, avoidance, interpersonal difficulties, and health problems. In each
      section, the potential impact of past sexual abuse on current breastfeeding
      behavior and the mother-infant relationship is described. Finally, specific
      suggestions and strategies for lactation consultants are offered.

PMID- 9775846
TI  - A case report of breastfeeding quadruplets: factors perceived as affecting
      breastfeeding.
AB  - The number of higher-order multiple births in the United States quadrupled
      between 1970 and 1994. The number of women choosing to breastfeed their higher
      order multiples also has risen. In this report, a mother of quadruplets
      identifies factors and interventions she perceived as having a positive or
      negative impact on breastfeeding. Maternal motivation coupled with a mother's
      personal approach to breastfeeding quadruplets may be key factors in shaping
      breastfeeding outcomes, such as in this case where one quad weaned at 12 months
      and the remaining three breastfed for 2 1/2 years. With increased discussion of
      this select population, lactation consultants and other health professionals will
      be able to develop breastfeeding care plans which reflect this population's
      unique needs and concerns from the prenatal through postpartum periods.

PMID- 9775847
TI  - True insufficient milk is rare.

PMID- 9775848
TI  - Breastfeeding the infant/child with a cardiac defect: an informal survey.
AB  - Despite the well-established benefits of breastfeeding, there is little
      literature about breastfeeding the infant with a congenital cardiac defect. This
      paper describes the experience of 12 mothers of infants with cardiac defects.
      These mothers responded to an informal survey and described numerous obstacles to
      success such as maternal fatigue, anxiety, separation from infant, institutional
      policy, and lack of support from health care providers. Mothers compared sources
      of help and identified coping strategies. Perceived benefits of breastfeeding
      included decreased illness, decreased stress, feeling part of the infant's health
      care team, and maintaining a relationship with the infant. Recommendations for
      assisting the mother nursing an infant with congenital heart disease are
      included.

PMID- 9775849
TI  - Clinical case history: donor milk use for severe gastroesophageal reflux in an
      adult.

PMID- 9775850
TI  - Nicotine replacement products: implications for the breastfeeding mother.

PMID- 9775851
TI  - [Pain therapy for the severely ill and the dying].

PMID- 9775852
TI  - [Etiology and diagnosis of fever of unknown origin].

PMID- 9775853
TI  - [The virus can not yet be eradicated. "HIV-infected patients cannot be completely
      cured"].

PMID- 9775854
TI  - [Cost comparison. Conventional care of wounds versus modern care of wounds].

PMID- 9775855
TI  - [Dialog with the anesthetist before surgery: something of help to the patient and
      his carers].

PMID- 9775856
TI  - [Geriatrics and enterostomal therapy: "The arena of everyday living is
      important"].

PMID- 9775858
TI  - [ALCATEL--telecommunication in the hospital].

PMID- 9775857
TI  - [Placing workers where their competence counts].

PMID- 9775859
TI  - [Religious requirements in old age. How do I find out about religious
      requirements and problems in the care of the aged].

PMID- 9775860
TI  - [Psychologists who founded schools (V). C.G. Jung--Wilhelm Bitter (1893-1974)].

PMID- 9775861
TI  - Specialist practice: the long road to a set of standards.

PMID- 9775862
TI  - Writing and presenting a research report.

PMID- 9775863
TI  - Helping supervisees to get the most out of their supervisory experience.

PMID- 9775864
TI  - Neither this nor that: the stigma of being an undergraduate nurse.

PMID- 9775865
TI  - Lecturing in higher education: a career for self-starters.

PMID- 9775866
TI  - Sharing education.

PMID- 9775867
TI  - Introducing a nursing doctorate.

PMID- 9775868
TI  - Learning in clinical practice. 2. Building relationships.

PMID- 9775870
TI  - Supervision for nurse specialists.

PMID- 9775869
TI  - Professional relationships: authority and power.

PMID- 9775871
TI  - Working in the community.

PMID- 9775872
TI  - Myths and facts...about botulism.

PMID- 9775873
TI  - Caring for venous ulcers.

PMID- 9775874
TI  - Pain Management. Worlds apart.

PMID- 9775875
TI  - Documenting suspected child abuse, Part II.

PMID- 9775876
TI  - Managing wound dehiscence and evisceration.

PMID- 9775877
TI  - Lithium and sodium depletion.

PMID- 9775878
TI  - Pulse oximeters.

PMID- 9775879
TI  - Actionstat. Ruptured diverticulum.

PMID- 9775880
TI  - Danger points. How to prevent nerve injuries from venipuncture.

PMID- 9775881
TI  - Getting in touch with Rita.

PMID- 9775882
TI  - Reaching beyond the rules. Understanding--and influencing--your scope of
      practice.

PMID- 9775883
TI  - "Thank God I have cancer".

PMID- 9775884
TI  - Female genital mutilation.

PMID- 9775885
TI  - Your patient is undergoing resuscitation. Where's the family?

PMID- 9775886
TI  - Nutrition during drug therapy.

PMID- 9775887
TI  - Sounding out blood flow with a Doppler device.

PMID- 9775888
TI  - End-of-life care. How well do we serve our patients?

PMID- 9775889
TI  - Sweeping away stereotypes.

PMID- 9775891
TI  - 30 rules to live by.

PMID- 9775890
TI  - Resolving conflicts. It's as easy as 1-2-3.

PMID- 9775892
TI  - Coping with HPV. How to help a patient diagnosed with this sexually transmitted
      disease.

PMID- 9775893
TI  - I'm not going anywhere.

PMID- 9775895
TI  - Protesting sexual harassment. Was this a hostile work environment.

PMID- 9775897
TI  - The UKCC's specialist practice consultation period.

PMID- 9775896
TI  - Sharing. Pretty in pink.

PMID- 9775898
TI  - Victory for partnership.

PMID- 9775899
TI  - Crossing the divide.

PMID- 9775900
TI  - Bearing in mind.

PMID- 9775901
TI  - Show you care.

PMID- 9775902
TI  - On your mark. Stop.

PMID- 9775903
TI  - Rebels with cause.

PMID- 9775904
TI  - Dead letter.

PMID- 9775905
TI  - Surveying Europe.

PMID- 9775906
TI  - All change.

PMID- 9775907
TI  - Networks for the rich?

PMID- 9775908
TI  - Research & development co-ordinating centre.
AB  - This year the RCN launched its Research and Development Co-ordinating Centre, the
      main focus of which is a web site that allows nurses to access extensive R&D
      related information on a range of topics. In this report, the authors explain the
      benefits for nurses and patients and how interacting with the site will shape its
      future development.

PMID- 9775909
TI  - Personal professional profiles.
AB  - This article reports the results of a study into the use of personal professional
      profiles by nurses, midwives and health visitors in an NHS trust. The author
      discusses factors in profile development, compares profile use between grades and
      attempts to identify the need for in-service education and support for profile
      development.

PMID- 9775910
TI  - CFC-free inhalers.

PMID- 9775911
TI  - Interstitial cystitis.
AB  - Interstitial cystitis (IC) is a serious debilitating disease often overlooked by
      medical and health professionals. This paper describes the elusive aetiology and
      the painful symptoms of IC and how it affects the patient's life. The author
      outlines the treatments available and offers guidelines for supporting patients
      with the disease.

PMID- 9775912
TI  - Ectopic pregnancy.
AB  - This article discusses the aetiology of tubal ectopic pregnancy and the
      associated risk factors, methods of diagnosis and treatment options, so that
      nurses will be better informed and feel more confident when advising and nursing
      patients.

PMID- 9775913
TI  - Nursing's role in interdisciplinary accountability for patient outcomes.
AB  - Few disagree that health care is improved by effective interdisciplinary
      teamwork. Most nurses are anxious to collaborate with members of other
      disciplines in the delivery of cost-effective care. Unfortunately, some overly
      zealous and mistaken proponents of the interdisciplinary approach argue that a
      disciplinary focus is incongruous with interdisciplinary teamwork. Nurses must
      resist this notion, work to strengthen the discipline, and gain the tools needed
      to be visible and accountable. Nursing has an important role in interdisciplinary
      care, and interdisciplinary teams depend on nurses' contributions to be effective
      and accountable.

PMID- 9775915
TI  - Implementing the Nursing Outcomes Classification in a practice setting.
AB  - Outcomes management has received increased attention in the current health care
      environment, but nursing participation has been limited due to the lack of
      standardized data about the effects of nursing practice. The Nursing Outcomes
      Classification (NOC) provides a standardized language that can be used to measure
      the effects of nursing practice on patient outcomes. An overview of the
      classification and implementation methods is provided.

PMID- 9775914
TI  - Collaborative practice teams: from multidisciplinary to interdisciplinary.
AB  - The current competitive health care market includes consumers and payers who are
      demanding that providers demonstrate and validate the effectiveness of their
      interventions in promoting patient outcomes. Collaboration in the form of
      interdisciplinary teams is an effective mechanism for enhancing patient outcomes.
      The CPT acts as the vehicle for driving the outcomes management process. Seven
      skills used by CPT members enhance collaboration: clinical competence,
      credibility, consistency, assertiveness, structured meetings, valuing of time,
      and marketing of the CPT. Change is inevitable, and strategies for change will be
      useful in achieving the outcomes of carefully planned objectives and goals.

PMID- 9775917
TI  - The Outcomes Research in Nursing Administration Project: methodological issues in
      implementation.
AB  - This article describes the Outcomes Research in Nursing Administration (ORNA)
      project--a longitudinal, multisite study investigating the interrelationships of
      various hospital-level and nursing-unit-level characteristics, nursing unit
      organizational structure, and administrative and patient outcomes. A variety of
      methodological challenges were encountered in the actual conduct of the project
      in relation to the design, sampling plan, management of attrition, and data
      collection. The article describes these challenges and how they were successfully
      resolved.

PMID- 9775916
TI  - Dignified dying as a nursing outcome.
AB  - The goal for humanistic end-of-life care is to maintain quality of life and
      personal dignity. The nursing outcome called "dignified dying" is defined as
      maintaining personal control and comfort with the approaching end of life and
      lists indicators for measuring this. These criteria enable nurses to measure the
      effectiveness of their nursing interventions, monitor patient progress over time,
      and summarize research data. This article describes the development of this
      outcome and illustrates its use with a case study.

PMID- 9775918
TI  - Impact of risk classification on nursing resource utilization, postoperative
      length of stay, and hospital costs for cardiac surgical patients.
AB  - Outcomes after cardiac surgery are a concern for patients, health care providers,
      and insurers. Because of the current economic climate, there is a demand for
      positive outcomes and an evaluation of negative results. The results of this
      study showed significant differences in nursing resource utilization,
      postoperative length of stay, and hospital costs by risk classification group.
      Risk classification models could serve as a template for staffing patterns and
      reimbursement based on patients' clinical profiles.

PMID- 9775919
TI  - Nursing performance measures go public.
AB  - Over 100 years ago, Florence Nightingale showed caregivers how to analyze
      mortality data to improve their clinical processes. The nurses of today are
      facing a new performance measurement challenge. Consumers of health care services
      want information that will help them compare quality among providers. This
      article describes the types of nursing performance measures most appropriate to
      include on these public-oriented report cards and several issues that influence
      report card design and dissemination.

PMID- 9775920
TI  - The relationship of hospital structural and financial characteristics to
      mortality and length of stay in acute myocardial infarction patients.
AB  - This ex post facto correlational study reports the influence of eight hospital
      structural and financial characteristics on mortality and length of stay (LOS) in
      acute myocardial infarction patients in 373 California hospitals. Significant
      results include: registered nurse hours/patient day (RN hours/pt. day) were
      inversely related to mortality in bivariate and regression analyses and to LOS in
      regression analyses. Total operating expenses/patient day (TOE/pt. day) were
      positively related to mortality (regression analyses) and LOS (bivariate
      analysis). The authors discuss implications for research and administration.

PMID- 9775921
TI  - [Modernizing nursing with holistic nursing systems? Results of a formative
      assessment].
AB  - A project aiming at the implementation of a holistic nursing system was conducted
      on selected wards of a general hospital. The results of a formative evaluation
      are presented from a work psychological perspective. The reorganisation of
      nursing led to a higher degree of patient and employee orientation. Most aspects
      of nurses' work load were reduced but the improvement did not effect nurses'
      strain to the expected degree. Decision latitudes at the workplace were enlarged,
      whereas only few changes in decision latitudes were stated with regard to areas
      outside the ward. The project is discussed as a reflexive strategy of
      modernization; its success is a result of a process-oriented management which is
      able to react on unavoidable consequences in the reorganization process.

PMID- 9775922
TI  - [Patient-oriented quality assurance. Information and cooperation of the health
      services as a condition for integrated care].
AB  - The increasing care needs of the elderly and chronically ill have a growing
      impact on health care services. With complex needs to meet, the patient's quality
      of life depends on multiple factors, of which the continuity of care plays an
      important role. Information on the past and present health state and on self care
      resources are prerequisites for adequate rehabilitation efforts that are patient
      oriented and of high quality. Institutionally induced "cascade episodes of
      incompetence" (Ulmer & Saller, 1994) have to be avoided. To make sure that
      interventions promote or stabilize the quality of life, the participation of the
      client is crucial in all stages of the process of care planning and coordination.
      Integrated care requires the exchange of information and close coordination on
      the concept of care between all participants in the care process. Yet,
      collaborative care is often seriously jeopardized by lack of knowledge about the
      concepts, scope of action and requests of the involved health professionals and
      services. At the Agnes Karll Institute of Nursing Research an action research
      project aiming at cooperative quality assurance was carried out. It became
      obvious that there is a large amount of intersectoral knowledge necessarily
      needed by all professionals and services to ensure seamless professional care.
      But often they have no access to the information needed. Therefore a client's
      accompanying booklet was developed to pass on basic information. It is kept by
      the client and shall be used and filled out by them, their relatives and the
      different health professionals and health care services involved.

PMID- 9775923
TI  - [Conceptual considerations on the use of nursing standards].
AB  - The article mainly focuses on basic questions and aspects as regards "nursing
      care standards", and how they have been discussed in specialist German literature
      during the past few years. Importance and function of standards to assure the
      quality of nursing are discussed. Requirements as well as conceptual
      considerations and aspects of content are shown. The necessity of checking
      standards and criteria is emphasized.

PMID- 9775924
TI  - [Pleasures and pains of a beginning researcher. What is being withheld at the
      presentation of a study].
AB  - This article endeavours to provide information about the process of conducting
      research. In presenting research, details of this process are often overlooked
      and left out. As these are part of the development of a study, the importance of
      such information seems obvious. Therefore highlighting and illustrating crucial
      phases of conducting research may not only provide background information to one
      particular study, but also provide a basis of comparison for other researchers.
      The article focuses on researchers who have just started their first study.
      Drawing on my personal experiences as a junior researcher, I will attempt to
      point out the difficult, but also the joyous parts in conducting research.

PMID- 9775925
TI  - [Foot reflexology: an intervention study].
AB  - The study's goal was to test if foot reflexology (FR) affects well-being,
      voiding, bowel movements, pain and/or sleep in women who underwent an abdominal
      operation. 130 subjects were randomized into three groups. For five days they
      were exposed to 15 minutes of FR, foot/leg massage (FM) or talking respectively.
      Results show that women in the FR group were more able to void without problems,
      after the indwelling catheter had been removed, than did women in the comparison
      groups. There was also a tendency in the FR-group for the indwelling catheter to
      be removed earlier than in the other groups. In comparison, the FR-subjects slept
      worse than the others. FM showed significant results in subjective measurements
      of well-being, pain and sleep.

PMID- 9775926
TI  - [Ethics and nursing. A contribution to nursing education].
AB  - Given today's developments in public health, nursing will be forced to manage
      different care services in the future. Nurses' growing responsibilities and the
      complexity of decision-making increase the necessity of a discussion of ethics in
      nursing. Ethics should help nurses solve moral conflicts. This article (an
      excerpt from a thesis) describes one possible way to improve ethical decision
      making: by using casuistry as an attempt to help nurses bridge the gulf between
      general moral rules and specific problems in specific cases, for example the
      conflict between respecting autonomy and the obligation to care, one of the main
      problems of decision-making. This problem is analyzed according to Thiroux's
      ethical principles. The limits of casuistry lie in the fact that each person is
      accountable for his own decision in a specific situation without having a
      relevant context to refer to.

PMID- 9775927
TI  - [Old, in need of care and homosexual. Experiences of an patient and his nursing
      team].
AB  - As many other homosexuals of his generation, Mr. X had to lead to double life.
      Now over 80 years old, he continues to live according to its rules. His
      behaviour, his effeminate nature and his sexual reactions evoke feelings of
      disgust, anger and rejection-emotions that have a relieving effect on the team.
      Those members of the nursing staff that allow these emotions to arise assume that
      Mr. X makes use of nursing care as a means of sexual stimulation. Both patient
      and team suffer from this situation. On the other hand there are also moments of
      true affection and fascination. This qualitative individual study gives a
      methodological framework for research by using interpretative biography. The
      results show how social contempt, involuntary prejudices and mental hospitalism
      serve each other's purposes.

PMID- 9775929
TI  - [Nursing, a quality service? The patient answers].
AB  - Being quality an updated concept in several productive sectors, we have tried to
      study this concept in nursing service environment at the patient's point of view.
      For reaching this goal, a questionnaire has been made upon which 45 Hospital de
      Clinicas de Porto Alegre interned patients have produced their opinions. It has
      been shown that generally speaking, the nursing service has been satisfactory
      although there is some critic from some clients and improvement could be worked
      out.

PMID- 9775930
TI  - [Support for decision making in nursing in cases of altered urinary elimination:
      Alturin.Exp System].
AB  - Lopes, Palombo and Sabbatini have developed a system for computer-aided decision
      in nursing named ALTURIN.EXP, based on SABBATINI'S EXPERTMD system and the North
      American Nursing Diagnosis Association (NANDA) nursing diagnosis classification,
      which is related to nursing diagnosis for altered urinary elimination. The
      ALTURIN.EXP defines the specific altered urinary elimination diagnosis and
      indicates the most common nursing interventions. Our purpose was testing the
      program clinically. Twenty-nine cases of altered urinary elimination in women
      with gynecological and oncogynecological problems have been described. Three
      nurses provided the principal and secondary diagnoses when regarded. These
      diagnoses were compared to those of the program. As previously elaborated, the
      program, in some cases, provided the secondary diagnosis. The clinical cases use
      has led to a review on the program structure in order to decrease error
      possibility.

PMID- 9775931
TI  - [Patterns in nursing supervision at hospitals in Feira de Santana-Ba].
AB  - This is an exploratory descriptive study about Nurse Supervision Pattern (NSP)
      performed in Feira de Santana-Bahia-Brazil, in 1994, which aims at describing
      supervision pattern and identifying interference factors. A questionnaire and
      descriptive statistics have been used. Supervision pattern proved that the kind
      of hospital is a factor that interferes on NSP. Based on literature, percentual
      exam of results and author's professional experience, it asserted that sex,
      academic graduation, earnings, health politics, planning and technical
      administrative structure are conditional factors for NSP, as well as lack of
      professional autonomy, interference of political parties, deficiency of material
      and human resources, low salaries, unsuitable environment and unsatisfactory
      interpersonal relationships mentioned by the subjects.

PMID- 9775933
TI  - [The mother figure of children with malformations. A phenomenological study].
AB  - The theme of this research refers to children suffering congenital malformation
      through an analysis of their mothers' reactions in dealing with such a situation.
      It deals with a descriptive study along the qualitative line through the
      phenomenological approach. In order to attain that purpose, interviews were made
      and data collected. The analysis was built under the view of meaning, the
      orientation of those mothers, i.e. the outlook of the world from their
      perspective, which was tracked from the meanings (units of meaning) to actual
      sense based on the philosophical insight of Dr. Martin Heidegger, aiming at
      characterizing the mother-being in her daily life.

PMID- 9775932
TI  - [Expectations of hospitalized patients as to their relationship with the nursing
      team].
AB  - This research has been made in infectious-parasitary disease sector of a public
      university hospital in Rio de Janeiro on the first semester of 1995. The logbook
      research has been introduced to 5 adult clients, from both sexes, who had been
      interned in the construction of two categories, which are: a) Category I:
      Feelings and expectations of the client and; b) Category II: Communication and
      relationship between client and nurse. The results found in the first category
      were: 1) Lack of affection; 2) Affection, fear and anxiety; 3) Loneliness and
      depression; 4) Reflection; 5) Insecurity; 6) Worry about the equipment, to be
      cut, to be impersonally treated, lose self-control and physical dependence. The
      results found in the second category were: 1) Doubts and interests in information
      about their disease, its evolution and how long they will stay in hospital: 2)
      Opportunity to express feelings and ideas; 3) Comprehension of the message given
      by the nurse. We emphasize the increase of interchange of information, ideas,
      beliefs, feelings and acts in nurse-client interaction to develop the therapeutic
      relationship aiming at helping the client to fulfill his basic needs.

PMID- 9775934
TI  - [The search for lost places. Help for the mental patient made possible through
      his life history].
AB  - This study aims at knowing mental patients life history by freeing their hopes,
      projects and possibilities either indoors or away from the psychiatric
      institution and based on the people knowledge of life, pondering over assistance
      to mental patients. By reading speeches reports, we have been revealed their
      quality of life BEFORE, DURING and AFTER the maddening process, considering that
      for AFTER, the reports presented another meaning, even when the place was
      materially the same place of before becoming ill. Due to the lack of choice and
      of meaning, they succeeded in living looking backwards to the past, which, in
      most cases, was also plenty of difficulties; however they had the essential: the
      role they played was socially accepted, they shared the social group and
      anticipated the time-to-come. The subject of this study exposed the use of
      astuteness and smartness to dribble the rules to which they are submitted. They
      reinvindicate the liberation of the identity, the relational, they wish to share
      life with the others and participate in the administration of their destiny,
      somehow. They also state that the non-place, is not only the psychiatric hospital
      but also the existing culture of mad-houses in the families, out-patient units,
      daily hospitals and hospital psychiatric wards. Undoing the mad-house, it will be
      necessary to revise culture or mental mad-house, in other words, to free our
      minds from rationality of jail. This is not only a process within Psychiatry; it
      crosses different dimensions: politics, law, social organizations, rules,
      disciplinary institutions, the collective imaginary.

PMID- 9775935
TI  - [Operational definition of the quality of nursing care at an intensive care unit
      of a teaching hospital].
AB  - The purpose of this study is the development of valid standards and criteria of
      nursing care quality for intensive care units (ICUs) based on Donabedian's
      approach to quality access. Eighteen standards and 219 criteria have been
      formulated by ICU staff nurses at a school-hospital, according to a protocol.
      These standards/criteria have then been evaluated by 14 experts in ICU Nursing
      from 5 other hospitals by means of a written questionnaire. The results indicated
      a high acceptance thereof and only one criterion was rejected. This showed that
      staff nurses and the experts involved had similar concepts about quality of ICU
      practice. The developed operational definition may be a basis to quality access
      tool. Staff nurses participation in this process is recommended.

PMID- 9775936
TI  - [Use of a brainstorming technique for decision making by a public health nursing
      team].
AB  - The study focuses on the use of brainstorming tool for consensual decision making
      in nursing services. A qualitative research has been developed with focus group
      technique use involving 6 workers from a basic health unit in Joao Pessoa city
      which belongs to the state network of Paraiba State Health Secretary. The results
      showed the method application plausibility as a strategy to nursing services
      quality improvement.

PMID- 9775937
TI  - [Drug combinations in the care of bed sores].
AB  - The present study aims at discussing the types of prescriptions and caring
      bedsores related to IRUXOL ointment use, as well as bandages practice reports
      performed by the nursing team in care units. Nineteen patient files from three
      School Hospitals ins Rio de Janeiro city have been analyzed. The results
      presented eight different kinds of drug prescription for bedsore treatment in
      which four of them were related to IRUXOL. The most frequent formulation was:
      cleaning with PVP-I + Physiologic Solution 0.9% and IRUXOL. It has also been
      observed that the nursing professional had used seventeen different combinations
      with several substances in which ten of them were associated to IRUXOL. They have
      also reported the use of 24 different products/substances when performing
      bedsores bandages. The indiscriminated use of products which alters injury pH
      (acid-base contents) such a factor which interferes debridant action of IRUXOL,
      has been verified.

PMID- 9775938
TI  - [The nurse's role today].
AB  - This work aims at analyzing the nurse's role as a result of historical
      transformations that happened in nursing. The capitalist system sets the nurse in
      an assistance clinical model which is designated to other professional areas,
      often without any qualification. In this universe, we understand that the nurse
      has the main role of administrating the nursing assistance for having a vision of
      the whole and, this way, develop a qualified and articulated service provision
      for nowadays social structure needs.

PMID- 9775939
TI  - [Nursing research on the use of venous catheters for hospitalized patients].
AB  - This report shows that intravenous catheterisation has been required for 59.4% of
      the patients in this sample. The main reason identified for catheterisation was
      the difficulty in accessing peripheral veins. The wound dressing was applied for
      100% of the patients and the procedure itself was carried out each 48 hours in
      89.8% of them. The intravenous catheter stood for 10 days in 52% of the cases and
      it was removed in 34.8% for intravenous drugs interruption and the other reasons
      were related as to technical problems. The most present microorganism was
      Staphylococcus aureus in 20.3% of the catheter cultures.

PMID- 9775941
TI  - [Understanding the idea of nursing for use in professional practice].
AB  - This study is about the comprehension analysis of female students at graduation
      courses in Nursing on the meaning of Nursing as a female profession, in the light
      of their reasons why they have chosen it. Qualitative method and social
      representation have been used for data analysis. The results showed that Nursing
      is a profession of love for the fellowman and it is a way to get closer to God,
      but it is also a challenge and a struggle for a better profession.

PMID- 9775942
TI  - [Work and manifest: the esthetic challenge to health workers].
AB  - This work goal is the aesthetic of health work, aesthetic seen as the fundamental
      relation between Man and the world, thus the individual way of happening in any
      praxis. It analyses the space of aesthetic expression of health workers, through
      the most quotidian thought, action, and manifestation. It discusses the object in
      the sociological and philosophical landmark and presents some categories
      generated from a qualitative research process. It recovers time-space-subject
      relation as well as the importance of imagination and the symbolism in health
      work comprehension, especially on work and subjectivity relation and on worker
      ethical aesthetic deviation rescue-turn work into an experience of self
      enunciation.

PMID- 9775943
TI  - [Daily circadian variations of deaths in a general hospital].
AB  - This work aims at determining the incidence of circadian daily variations of
      natural death at a general hospital. METHODS: We have analyzed time of death in
      502 individuals with natural death. Statistical analyses have been applied to
      determine the difference significance between proportions and averages. As a
      result, we have found out that the occurrence of natural death was similar in
      different periods of the day. However, values indicate an excess of lethality at
      6 a.m. and from noon to 6 p.m. We have concluded that the observed results
      suggested that the natural death does not have a circadian pattern, despite the
      vespertine peak.

PMID- 9775944
TI  - [Nursing and its practice: thinking and experiences of nurses at the St. Francis
      of Assisi Teaching Hospital].
AB  - This research is of qualitative nature and it aims at studying nurse's social
      representations towards nursing and its professional practice and the way they
      effectively accomplish this practice at Rio de Janeiro Federal University San
      Francisco de Assisi School Hospital (HESFA/UFRJ). Data were collected from
      interview, campus observations and documents. Data analysis reveal contradictions
      and conflicts experienced by nurses in their professional praxis. They are
      beginning a process of reflection on their professional autonomy: they are sorry
      for the lack of structure is assisting clients properly; they do believe that
      researching and political participation are essential for profession development.

PMID- 9775945
TI  - [Holistic practice in nursing: problems, experiences and potentials].
AB  - This work aims at seeking possibilities of advances in Nursing through intimate,
      daily and social holopraxis. We believe that holopraxis favors a better view of
      health/illness process and, consequently, it results in upgrading health care
      delivery quality, allowing partial or total difficulties overcome in Nursing
      exercise.

PMID- 9775946
TI  - [Power, interdependence and complementarity in hospital work: an analysis from
      the nursing point of view].
AB  - This essay intends to discuss recent transformation both to hospital work and
      nursing work specifically. Analysis privilege inter and intra relations with
      multidisciplinary teams which is constituted of practices on the therapeutic
      process present in hospital space-time.

PMID- 9775947
TI  - [Risk factors for the spine: nursing assessment and care].
AB  - The present work aimed at studying risk factor that affect people with back pain,
      identifying them and implementing an intervention proposal of a health education
      program based on self-care teaching, existential humanist philosophical projects
      and stress equalization approach line, skeletal-muscle reintegration activities,
      basic techniques on stress equalization and massage. It has been developed for a
      population of 42 (forty-two) clients. Two instruments which integrate nursing
      consultation protocol have been used in data collection. The results showed the
      existence of associated risk factors which are changeable according to health
      education programs. The assessment process has contributed for therapeutic
      measures focus, using non-conventional care methods for this approach providing
      an improvement to these clients life quality.

PMID- 9775948
TI  - [Creating an integrated nursing curriculum].
AB  - During the last two decades, Brazilian society has gone through great changes
      into political, ideological and economical fields. These changes left their
      strings into society, specially in population health. The nurse formation based
      on the Law n(o) 5540/68 and on the Statement n(o) 163/72, no more meets
      population demands. Since 1992, the Nursing Faculty of UERJ-FEUerj intensifies
      the reflection movement upon teaching-learning process searching for transforming
      its own reality. The making of this project presents two complementary and
      important reasons: FEUerj docents and discents' desire in elaborating a
      curriculum which searches for nurses' formation that articulates teaching-work
      community, theory and practice, based on a Critical Theory of Education, on the
      line of PROBLEMATIZATION, and the accomplishment of Statement n(o) 314/94 from
      the CFE and from the Letter of Order MEC n(o) 1171/15/dez/94. From debating, the
      professional profile has been defined from the social environment where the
      profession is performed and the alumnate's characteristics; area determination or
      group of attributions, according to professional praxis adequation, concept
      hierachization, processes, etc., which in the process of 'classification and
      syntheses' of knowledge results into a netlike chained and related tree. In the
      first phase of the curriculum study, it has diagnosed as principal condition, the
      actual curriculum 'DECONTEXTUALIZATION' and the 'US' to be faced to lead it to an
      end the Curriculum Reformulation Proposal. The Process of Pedagogical Abilitation
      for professors, workshops, researches on the desirable and present profile,
      seminars, performance, abilities and principles systematization, identification
      of areas which compose the integrated curriculum, subjects localization into
      areas and articulation between professional subjects and other activities, has
      been implemented. Based on this work on the problematized pedagogy first step, an
      instrument 'Research on the Professional Profile for the Nursing Graduation
      Course', was built, identifying the performances and principles which sustain
      them on each subject making the present profile clear and desirable to docents
      and discents.

PMID- 9775949
TI  - [Illness, hospitalization and anxiety: an approach to mental health].
AB  - With the purpose of completely approaching the patient in the hospital, this
      research had the goal to identify the generating factors of the of anxiety
      patient and how they express their uneasiness towards the illness and the
      hospitalization the data were collected from april/may/96 with adults in a school
      hospital and was based on a guide for observation of the anxieting situations and
      in an interview guide. We found out that the patients' major concerns were:
      Knowing if their illness has aure, how long they will be there, their and the
      support of the family. They get sadder at night and in the afternoon, when the
      staff is reduced, there is more silence and they feel lonely. Only a small
      percentage of them have the consistent information about the disease and
      treatment, however, the hospital is mainly identified as a good place for the
      possibility of cure, good assistance and food. Witnessing the suffering and the
      dying risk of the neighbour, be discharged, exams and treatment procedures
      suspended on cancelled, bling communicated of the necessity of bling operated on
      that the disease doesn't have a cure, were the anxieting factors that were
      remanked not only in the immediate sections, but also in the late ones of the
      anxieting situations, prevail passive attitudes such as sadness, crying,
      depression and negativism. We concluded that the psychic and emotional conditions
      of the patients in the hospital have to be taken on consideration on hospitals
      emphasizing a comsiete approach, with special care of the speed of the actions
      and the consistence of the information given to the patient about their health
      and treatment.

PMID- 9775950
TI  - [Seventieth anniversary of the Brazilian Nursing Association].
AB  - The celebration of the Brazilian Nursing Association seventieth anniversary,
      former Brazilian Graduated Nurses Association, represents, in fact, seventy years
      of the history of Nursing in Brazil. We have certified, in a historical
      retrospective that the entity's creation, its organization which has been through
      several changes, adapting itself to the demands imposed by the conjunctures; the
      cultural landmarks, where the Brazilian Nursing Magazine, Brazilian Nursing Week,
      National Seminar of Research in Nursing, the Nursing Regional Meetings and the
      Brazilian Congress of Nursing are highlighted and are a demonstration of power
      and guts of this entity that survives from the struggle, conquests and
      achievements for the category. We also highlight the political advance these last
      two decades for the political and structural organization, the more democratic
      decisory process both internal and externally (ABEn's National Council); an
      autonomous social and political expression while civil society, better
      relationship with other national and international entities. Finally, we relate
      the challenges which appear to the entity's present management.

PMID- 9775951
TI  - [Is there one autism or are there several kinds?].

PMID- 9775952
TI  - [Towards integrated care in autism].
AB  - Autism entails major consequences because it affects the development of family
      relations and social groups, and because of the uncertainty of its causes and of
      the choices of therapeutic and educational methods. The diversity of clinical
      pictures leads to the necessity of individualized programs thanks to a global
      evaluation of the difficulties and capacities of the child. The authors propose a
      comprehension of the disorder--independently of its causes--from an early
      disturbance of the development of interpersonal relations, especially emotional.
      Care aims at respecting the means of development the child has at his disposal by
      supporting his natural partners--family, social and educational milieu--and by
      adding direct intervention according to age, intensity and evolution of the
      disorder. The integration of these different means implies the networking of
      multiple and complementary structures.

PMID- 9775953
TI  - [Psychological-educational intervention for autistic children].
AB  - A "TEACCH" experience conducted in Lyon, France, with autistic children within
      the framework of an infant-juvenile psychiatric intersectory is described here:
      the proposal for an individualized educational project stems from the
      developmental possibilities of each child; taking children into care is inspired
      by Schopler's proposals: in a structured environment the child is placed in an
      educational setting; alternatives to verbal communication are also proposed to
      the children, who for the most part are non verbal. At the same time, work with
      families is put into place: it consists of support in the taking in charge by the
      parents on a daily basis of the handicap of the child: a broad place is given to
      the harmonization of help to the child in his different life contexts.
      Contribution and limits of this work are also discussed: the child's capacity to
      relax, the improvement of his relational capacities and his autonomy are
      noteworthy; restoration of quality of life and relation with families is clear;
      the child's mental deficit is obviously a limiting factor.

PMID- 9775954
TI  - [Case report. Therapeutic intervention using a "particular interest" of an
      autistic child with visual agnosia].
AB  - Although special education under its diverse forms is consensually recognized as
      the privileged area of pervasive developmental delay, there is little studies on
      re-education intervention for autistic persons of normal intelligence. This
      article presents a psychoeducative intervention with a three year old autistic
      boy in a pedopsychiatric day care centre. The interest of this observation is
      double. On the one hand, this child, aside from autism, is carrier of an
      exceptional ailment: visual agnosia. On the other hand, his "restrictive autistic
      interest", namely perceptive attraction and his questioning of a particular class
      of objects or a particular parameter of these objects were used as lever to bring
      him to improve his capacities of communication and social interactions.

PMID- 9775955
TI  - [Clinical report on pharmacological treatment of autism].
AB  - This article reviews the pharmacology of autism and briefly overviews its use,
      history and novelties. "Autism" does not refer to any pathophysiology currently
      known. And no drug or class of drugs can cure this illness which includes many.
      Before using drugs, efficient in relieving symptoms, it is important to consider
      the potential benefit of behavioral approaches. Developments in research give
      hope that drugs will cure or prevent this brain illness.

PMID- 9775956
TI  - [Diagnosis of pervasive developmental disorders without mental retardation and
      its impact on obtaining social and educational services in Quebec].
AB  - Pervasive developmental disorders without mental retardation is a new clinical
      category including high-functioning autism, Asperger syndrome and pervasive
      developmental disorder non otherwise specified. Its recognition is recent and
      still problematic in many regards. This article reviews the historical,
      theoretical and clinical relations between pervasive developmental disorders
      without mental retardation and bordering disorders. The consequences of an
      inadequate diagnosis on measures of assistance for these patients is also
      investigated. The authors conclude on the necessity in considering, independently
      of the diagnosis, the description of symptoms, the intellectual level and the
      adaptative level in order to take the most appropriate educational and
      psychosocial decisions regarding pervasive developmental disorders without mental
      retardation.

PMID- 9775957
TI  - [The theory of the mind of the autistic child].
AB  - Theory of the mind is the capacity to present oneself with the desires, beliefs
      and intentions of others. This capacity is acquired by children around the age of
      seven. However, a deficit of this theory is present in people with autism with a
      mental age equivalent or superior to seven years old. This difficulty seems to be
      explained by a developmental delay specific to the mechanism of the mind (Baron
      Cohen, 1989a). This delay seems to be associated to their own diagnostic
      criterias, namely their cognitive difficulties (Baron-Cohen, 1989b), deficit in
      speech capacities (Sparrevohn et Howie, 1995) and to their altercations in social
      interactions (Holroyd et Baron-Cohen, 1993). This article proposes a review of
      the literature on the issue of theory of the mind as well as a description of two
      approaches, namely executive functions and central coherence.

PMID- 9775958
TI  - [Diagnostic criteria of autism and Asperger's syndrome: similarities and
      differences].
AB  - The American Psychiatric Association's last version of the Diagnostic and
      Statistical Manual of Mental Disorders (DSM-IV; APA, 1994) identifies within
      pervasive developmental disorders five subgroups: (a) autistic disorder; (b)
      Rett's disorder; (c) childhood disintegrative disorder; (d) Asperger's disorder's
      and (e) pervasive developmental disorder not otherwise specified. However, the
      diagnosis of the different sub-groups is difficult to establish, particularly
      between autistic disorder and Asperger's disorder. This article exposes the
      diagnostic criteria of autism and Asperger's syndrome in order to illustrate the
      similarities and differences between the two disorders.

PMID- 9775959
TI  - [Beliefs of foster parents regarding the children in their care and their natural
      parents].
AB  - This exploratory research has been conducted with the objective of identifying
      the beliefs of foster parents towards children in their care and their natural
      families. Results show that foster parents have a number of beliefs that can harm
      the optimal exercise of their mandate. The major issues raised concern their
      initial motivation, their perceptions of the children's needs, their educational
      strategies, the nuances regarding usual parental role and their positions
      regarding the natural parents of foster children. This research constitutes a
      foundation for more adaptative interventions with regards to the context of
      placement, especially for the development of support and education services for
      foster parents.

PMID- 9775960
TI  - [Perception of social support given by health professionals according to the
      participants in a prenatal prevention program who live in extreme poverty].
AB  - One of the essential elements of the "Programme integre de prevention en
      perinatalite--Naitre-egaux-Grandir-en-san t" (Born Equal--Brought up Healthy) is
      to have a health professional offering general support to pregnant women living
      in poverty. This research is based on a secondary analysis of the transcriptions
      of interviews done in order to implement the program. The thematic content
      analysis was employed to analyze the women's perception of the support provided
      by the health professional, the relationship between client-professional, and the
      perceptions of these women about the impact that the social support had on their
      pregnancy experience. The categories of support that emerged from the analysis
      are: information support, emotional support, instrumental support, changing life
      style support, recreational support, and availability of support. The categories
      of impact perceived by the participants are: learning, changes in life style, to
      be in a good mood, and the use of community resources. A key element in the
      perception of support by the participants is the establishment of a relationship
      of trust between professional and client. This relationship of trust is important
      to the development of intimacy and to foster the perception of a more intense
      kind of support. Hence social support and the relationship of trust work in
      synergy and reinforce each other.

PMID- 9775961
TI  - [Vulnerability and mother-child interactions. Illustration of the necessary but
      insufficient conditions for the efficacy of early intervention].
AB  - The present study evaluates the impact of an early stimulation program for 24
      mother-infant (0-6 months) vulnerable dyads from the Monteregie region. These
      dyads participate in a series of ten stimulation workshops. Twenty four other
      dyads form a witness group. The program's major objective aims at developing
      positive interactions for the mother and stimulative interactions for the infant.
      The hypotheses state that at the end of the program, the mother from the
      intervention group will feel less isolated, possess a higher level of knowledge
      on the development of their child, perceive more positively the temperament of
      their child and have behaviors that are more contingent to their infants as well
      as more functional to this development. The two first hypotheses are not
      confirmed. However, at the end of the program, the mothers of the intervention
      group perceive the temperament of their child as foreseeable. Also, they imitate
      more frequently the verbal and facial behaviors of their infant and emit more
      vocalizations when they are interacting with the child. The discussion of results
      bears on the importance of modifying conditions in which the parent-child
      interactions are held to prevent deficits in the development of the children.

PMID- 9775962
TI  - [Psychodynamic approach to the addictive personality structure specific for
      alcohol and hard drugs].
AB  - The overconsumption of psychotropic substances is a major problem for
      contemporary societies. In the USA, 14.1% of the population between the age 15
      and 54 have experienced addiction problems to alcohol during their lives while as
      7.5% are addicted for life to other drugs (cannabis, cocaine, stimulants, etc).
      Many studies report that excessive consumption of alcohol, with or without
      illegal drug use, is associated to social conditions favoring the development of
      psychological distress and isolation. Although there are many studies on the
      differences between personality traits of alcoholics and drug users, few authors
      have examined the possibility to bring to the fore a specificity between the
      personality structures of the alcoholic and the drug user from a psychodynamic
      approach. This exploratory review of literature, first presents studies already
      conducted in order to identify common or distinct personality features for these
      types of addition. This article then reviews psychodynamic writings examining the
      possibility of a structural organization that is specific to addiction. Finally,
      the authors propose a few thoughts allowing to postulate on the existence of a
      structural organization specific to these two types of addiction.

PMID- 9775963
TI  - [Reflection on the project PSI-La Boussole].
AB  - The "Psi-La Boussole" project constitutes a model of coordination of services
      characterized by two currents: case management and coordination of Individualized
      Service Plan (ISP). Its objectives consists in improving autonomy, social
      integration and quality of life of persons with severe mental disorders, as well
      as reducing the burden of families and favor a partnership between different
      resources. From Spring 1992 to January 1996, in Quebec City, 28 people with
      mental disorder participated in the project. After presenting their profiles, a
      synthesis of the analysis of 8 history cases allows to put in light the
      particularities of the model and its functioning.

PMID- 9775964
TI  - [Participants of courses for personal growth: motives for participation and how
      the courses were experienced and consultation of other health services. An
      exploratory study].

PMID- 9775965
TI  - [Emergency or crisis].

PMID- 9775966
TI  - [Ambulatory care and emergency centers].

PMID- 9775967
TI  - [Ambulatory care and emergency centers].

PMID- 9775968
TI  - [Patient admission at the ambulatory therapeutic center].

PMID- 9775969
TI  - [Patient admission without problems?].

PMID- 9775970
TI  - [The admission interview].

PMID- 9775971
TI  - [From admission to continuity of care. Limits of the care in ambulatory care
      facilities].

PMID- 9775972
TI  - [Those demented people, heavens!].

PMID- 9775973
TI  - [The association of psyche and cancer].

PMID- 9775974
TI  - [Care, health and nursing].

PMID- 9775975
TI  - [What are the challenges for nursing in the XXI century?].

PMID- 9775976
TI  - [Controversy about a vaccine].

PMID- 9775977
TI  - [Drugs, between health and politics].

PMID- 9775978
TI  - Plasticity of Na,K-ATPase isoform expression in cultures of flat astrocytes:
      species differences in gene expression.
AB  - The Na,K-ATPase plays an active role in glial physiology, contributing to K+
      uptake as well as to the Na+ gradients used by other membrane carriers. There are
      multiple isoforms of Na,K-ATPase alpha and beta subunits, and different
      combinations result in different affinities for Na+ and K+. Isoform choice should
      thus influence K+ and Na+ homeostasis in astrocytes. Prior studies of astrocyte
      Na,K-ATPase subunit composition have produced apparently conflicting results,
      suggesting plasticity of gene expression. Purified flat astrocytes from the
      cerebral cortex and cerebellum of both mouse and rat were systematically
      investigated here. Using antibodies specific for the alpha1, alpha2, alpha3,
      beta1, beta2, and beta3 subunits, isoform level was assessed with Western blots,
      and cellular distribution was visualized with immunofluorescence. Although alpha1
      was always expressed, differences were observed in the expression of alpha2 and
      beta2, subunits that can be expressed in astrocytes in vivo and in coculture with
      neurons. In addition, abundant alpha subunit was expressed in rat astrocytes and
      in mouse cerebellar astrocytes without an equivalent level of any of the known
      beta isoforms, suggesting that an additional beta subunit important for glia is
      yet to be discovered. Conditions that have been shown to increase Na,K-ATPase
      activity in astrocyte cultures, such as dibutyryl cAMP, high extracellular K+,
      and glutamate, did not specifically induce missing subunits, suggesting that
      cellular interactions are required to alter the ion transporter phenotype.

PMID- 9775979
TI  - Neurotrophins regulate the function of cultured microglia.
AB  - Although the physiological role of neurotrophins in neuronal development and
      survival has been extensively investigated, their role in glial cell physiology
      remains to be elucidated. In the present study, we investigated the effects of
      neurotrophins on cultured microglia from newborn rat brain. All of the
      neurotrophins tested nerve growth factor (NGF), brain-derived neurotrophic factor
      (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), increased the secretion
      of plasminogen and urokinase type-plasminogen activator and specific activity of
      acid phosphatase, but suppressed the release of constitutively-produced and
      lipopolysaccharide-stimulated nitric oxide (NO) from microglia. The reverse
      transcription-polymerase chain reaction, immunocytochemical staining, and Western
      blotting revealed that cultured microglia express Trk A, B, and C, and low
      affinity NGF receptor, LNGFRp75. Neurotrophin was found to phosphorylate Trk A
      and B, and the neurotrophin-induced enhancement of plasminogen-secretion was
      suppressed by protein kinase inhibitor, K252a. Furthermore, neurotrophins caused
      an activation of transcription factor, NF-kappaB. These results indicate that the
      neurotrophin family regulate the function of microglia through Trk and/or
      LNGFRp75-mediated signal transduction.

PMID- 9775980
TI  - Chronically denervated rat Schwann cells respond to GGF in vitro.
AB  - C-erbB receptor/neuregulin signalling plays a significant role in Schwann cell
      function. In vivo, Schwann cells up-regulate expression of c-erbB receptors in
      the first month after injury, but receptor expression is down-regulated with time
      to levels that are not detectable immunohistochemically. The inability of
      chronically denervated Schwann cells to respond adequately to signals derived
      from regenerating axons may be one reason why delayed repair of an injured
      peripheral nerve frequently fails. We have examined the effects of GGF on
      denervated Schwann cells in vitro. A modified delayed dissociation technique was
      used to obtain adult rat Schwann cells from the distal stumps of transected
      sciatic nerves which had been acutely (7 days) or chronically (2-6 month)
      denervated. We found that in vitro denervated Schwann cells invariably expressed
      p75NTR and c-erbB receptors. There was a progressive decrease in total cell yield
      and the percentage of cells with Schwann cell phenotype (p75NTR and/S-100
      or/laminin or /GFAP or/c-erbB positive); proliferation rate; migratory potential;
      and expression of the cell adhesion molecules N-CAM and N-cadherin, with
      increasing time of denervation. Addition of GGF2 had a significant stimulatory
      effect upon Schwann cell proliferation and migration, and an increased proportion
      of Schwann cells expressed N-CAM and N-cadherin, suggesting that these responses
      were mediated via GGF/c-erbB signalling. Our results support the view that it may
      be possible to manipulate chronically denervated Schwann cells so that they
      become more responsive to signals derived from regrowing axons.

PMID- 9775981
TI  - Glial cell-specific differences in response to alkylation damage.
AB  - Oligodendrocytes are preferentially sensitive to the toxic, carcinogenic, and
      teratogenic effects of methylnitrosourea (MNU). The mechanisms responsible for
      this enhanced sensitivity have not been fully elucidated. One of the most
      vulnerable cellular targets for this chemical is mitochondrial DNA (mtDNA). To
      determine if differences in mtDNA damage and repair capacity exist among the
      different CNS glial cell types, the effects of MNU exposure on oligodendroglia,
      astroglia, and microglia cultured separately from neonatal rat brain were
      compared. Quantitative determinations of mtDNA initial break frequencies and
      repair efficiencies showed that whereas no cell type-specific differences in
      initial mtDNA damage were detected, mtDNA repair in oligodendrocytes,
      oligodendrocyte progenitors, and microglia was significantly reduced compared to
      that of astrocytes. In astrocytes, and all other cell types previously evaluated
      in our laboratory, >60% of N-methylpurines were removed from the mtDNA by 24 hr.
      In contrast, only 35% of lesions were removed from mtDNA of oligodendrocytes,
      oligodendrocyte progenitors, and microglia during the same time period.
      Mitochondrial perturbations by a variety of xenobiotics have been linked to
      apoptosis. In the present study, apoptosis, as determined by DNA laddering and
      ultrastructural analysis, was clearly induced by MNU treatment of cultured
      oligodendrocyte progenitors and microglia, but not in astroglia. These data
      demonstrate a correlation between diminished mtDNA repair capacity and the
      induction of apoptosis. However, further experimentation is necessary to
      determine if a causal relationship exists and contributes to the vulnerability of
      oligodendroglia following exposure to N-nitroso compounds in the environment or
      in chemotherapeutic regimen.

PMID- 9775982
TI  - Voltage-dependent membrane currents of cultured human neurofibromatosis type 2
      Schwann cells.
AB  - Previous experimental observations indicate that inhibition of voltage-dependent
      K+ currents suppresses proliferation of normal Schwann cells. In the present
      study we tested the opposite relationship, i.e., whether Schwann cells from
      tumors with abnormally high rates of proliferation would have an increase in
      membrane K+ currents. Whole-cell membrane currents were studied in cultured cells
      from schwannomas of two neurofibromatosis type 2 (NF2) patients (n = 53), one
      patient with a sporadic schwannoma (n = 22), and two control subjects (n = 41).
      Five different types of voltage-dependent membrane currents were found in all of
      the Schwann cells tested. Membrane depolarization activated outward K+ and Cl-
      currents; quinidine was found to block the K+ current (IC50 approximately 1
      microM), and NPPB reduced the Cl- current. Ba2+-sensitive inward rectifier K+
      currents, fast Na+ currents, and a transient, inactivating K+ current were less
      frequently observed. On average, NF2 cells were found to have statistically
      significant higher membrane potential and larger non-inactivating K+ outward
      current as compared to controls. Electrophysiological parameters of Schwann cells
      from a sporadic schwannoma showed a tendency for larger outward currents;
      however, the difference did not reach statistical significance. Together the data
      support the suggestion of a possible link between K+ outward current and
      proliferation of Schwann cells.

PMID- 9775983
TI  - Cultured astrocytes express functional receptors for galanin.
AB  - The neuropeptides galanin and calcitonin gene-related peptide (CGRP) are strongly
      up-regulated in motoneurons following axotomy. Earlier reports have suggested
      that peptides might be released from injured neurons to recruit surrounding glia.
      In this study, the effects of galanin and CGRP on cultured rat astrocytes were
      investigated using the expression of immediate early genes as a model for
      receptor-mediated transcriptional activation. Galanin was found to induce c-fos,
      junB, and Tis11 mRNA in cultured astrocytes, providing evidence for the presence
      of functional galanin receptors on neuroglial cells. In contrast, CGRP only led
      to the induction of c-fos and junB mRNA. Cholecystokinin (CCK-8) and substance P,
      which are also up-regulated in select motoneuron populations following axotomy,
      fail to induce immediate early genes in astrocytes, indicating specificity of
      neuropeptides in their ability to stimulate glial cells. The differential
      induction of immediate early gene expression by galanin and CGRP in astrocytes
      points to differences in intracellular signal transduction mechanisms. Whereas
      CGRP was found to stimulate the accumulation of cyclic AMP by 10- to 20-fold,
      galanin had no effect on basal cyclic AMP content. The effect of CGRP on cyclic
      AMP accumulation was completely reversed by the CGRP receptor antagonist, CGRP(8
      37). These results suggest roles for galanin and CGRP in the transcriptional
      activation of astrocytes.

PMID- 9775984
TI  - Peripheral nerve-stimulated macrophages simulate a peripheral nerve-like
      regenerative response in rat transected optic nerve.
AB  - We have previously demonstrated that the failure of the mammalian central nervous
      system (CNS) to regenerate following axonal injury is related to its
      immunosuppressive nature, which restricts the ability of both recruited blood
      borne monocytes and CNS-resident microglia to support a process of repair. In
      this study we show that transected optic nerve transplanted with macrophages
      stimulated by spontaneously regenerating nerve tissue, e.g., segments of
      peripheral nerve (sciatic nerve), exhibit axonal regrowth at least as far as the
      optic chiasma. Axonal regrowth was confirmed by double retrograde labeling of the
      injured optic axons, visualized in their cell bodies. Transplanted macrophages
      exposed to segments of CNS (optic) nerve were significantly less effective in
      inducing regrowth. Immunocytochemical analysis showed that the induced regrowth
      was correlated with a wide distribution of macrophages within the transplanted
      transected nerves. It was also correlated with an enhanced clearance of myelin,
      known to be inhibitory for regrowth and poorly eliminated after injury in the
      CNS. These results suggest that healing of the injured mammalian CNS, like
      healing of any other injured tissue, requires the partnership of the immune
      system, which is normally restricted, but that the restriction can be
      circumvented by transplantation of peripheral nerve-stimulated macrophages.

PMID- 9775986
TI  - Carnosine and beta-alanine release is stimulated by glutamatergic receptors in
      cultured rat oligodendrocytes.
AB  - Oligodendrocytes obtained from rat brain 0-2 A progenitor cells and
      differentiated in culture take up beta-alanine and synthesize carnosine (beta-Ala
      His). The present study was designed to determine whether carnosine and beta
      alanine are released from such cultures in response to some stimuli. An evoked
      release of these substances was not observed when the cells were incubated with 1
      mM glutamate or 0.3 mM kainate. Addition of 0.1 mM cyclothiazide (CTZ) to the
      corresponding stimulus was accompanied by a distinct peak of release consisting
      of both carnosine and beta-alanine. The efflux was blocked completely in the case
      of kainate and to 80% in the case of glutamate when 50 microM 6,7
      dinitroquinoxaline-2,3 (1H,4H)-dion (DNQX) was added to the cells at the same
      time as the receptor agonist. An increase of the efflux was observed in the
      presence of Zn2+. This effect was concentration-dependent. Total substitution of
      NaCl in the efflux medium by LiCl caused only a partial reduction of the release.
      GABA or 55 mM KCl showed only negligible effect. A large release of carnosine and
      beta-alanine was observed when oligodendrocyte cultures were treated with Ca2+
      ionophore A 23187. These results suggest that oligodendrocytes exhibit a
      glutamate receptor-mediated release of carnosine and beta-alanine. The release is
      dependent on elevated intracellular Ca2+ concentration.

PMID- 9775985
TI  - Elevated complement C5a receptor expression on neurons and glia in astrocyte
      targeted interleukin-3 transgenic mice.
AB  - Evidence from several central nervous system (CNS) inflammatory disease models
      suggests that intrathecal complement synthesis may contribute to early
      inflammatory events in the brain. In this study, we examined the expression of
      the receptor for C5a (C5aR), a potent inflammatory and chemotactic factor, in the
      brains of transgenic mice with constitutive astrocyte expression of interleukin-3
      (IL-3), a hematopoietic and immunomodulatory cytokine. By in situ hybridization,
      we demonstrated that cells infiltrating the cerebellar meninges, the cerebellum,
      and demyelinating lesions in the cerebellum were strongly positive for C5aR mRNA.
      By immunohistochemistry, the infiltrating cells expressing the C5aR were
      identified as macrophages based on staining with antibodies to the complement
      receptor type 3 and F4/80, a mouse macrophage-specific marker. In addition, some
      of the cells in cerebellar lesions were positive for the astrocyte-specific
      marker, glial fibrillary acidic protein, suggesting that a subpopulation of
      astrocytes in these lesions express elevated levels of the C5aR. Increased C5aR
      expression was also observed in cortical neurons in the occipital cortex and in
      pyramidal neurons in the cornu ammonis and subiculum of the hippocampus, at both
      the protein and mRNA levels. These data suggest that IL-3 may play an
      immunomodulatory role in C5aR expression on several cell types in the brain and
      that increased C5aR expression correlates with the pathology seen in this model.
      The transgenic mice used in this study provide a useful tool for characterizing
      the mechanism of regulation of the C5aR expression and for examining the
      functions of this chemotactic receptor in CNS inflammation.

PMID- 9775987
TI  - Two novel monoclonal antibodies (1.9.E and 4.11.C) against olfactory bulb
      ensheathing glia.
AB  - We produced and characterized two monoclonal antibodies, termed 1.9.E and 4.11.C,
      that specifically recognize olfactory bulb ensheathing glia. Both antibodies were
      generated using the olfactory nerve layer (ONL) of newborn rat olfactory bulbs
      (P0, P1) as immunogens. The specificity of these antibodies was tested by
      immunofluorescence techniques on tissue sections and cultures of adult and
      neonatal rat olfactory bulbs, and by Western blot analysis. 1.9.E labeled the ONL
      and glomerular layer of the olfactory bulb (OB) of adult rats. In newborn rats,
      1.9.E immunostained ensheathing cells from the ONL and peripheral olfactory
      fascicles. Furthermore, 1.9.E reacted with some processes of the radial glia in
      the periventricular germinal layer of the newborn rat. Although 4.11.C also
      specifically labeled ensheathing cells in the adult OB, it did not stain any cell
      type in the ONL of newborn rats. The lack of double labeling with either 1.9.E or
      4.11.C and anti-olfactory marker protein (OMP) antibody, a specific marker for
      olfactory axons, indicated that none of the monoclonals recognized olfactory
      axons. Double immunostaining of adult OB cultures with 1.9.E or 4.11.C and anti
      p75-nerve growth factor receptor revealed that both antibodies specifically
      recognized ensheathing glia in those cultures. Filaments were strongly labeled
      throughout the entire cytoplasm of ensheathing cells, suggesting that 1.9.E and
      4.11.C immunoreacted with ensheathing glia cytoskeleton. 4.11.C stained a few
      Schwann cells in adult sciatic nerve sections. Moreover, 4.11.C immunostained
      cortical astrocyte cultures from newborn rats (P1). In Western blot analysis both
      antibodies recognized a major component, migrating with an apparent molecular
      weight of 60 kDa, from olfactory nerve and glomerular layer (ONGL) extracts of
      adult and neonatal rats. The pattern of immunoreactivity of 1.9.E and 4.11.C
      antibodies suggest that both antibodies are specific markers for olfactory
      ensheathing glia in the adult rat central nervous system (CNS).

PMID- 9775988
TI  - Diltiazem for maintenance tocolysis of preterm labor: comparison to nifedipine in
      a randomized trial.
AB  - The objective of this study was to compare the safety and efficacy of maintenance
      tocolysis with oral diltiazem to oral nifedipine in achieving 37 weeks gestation.
      After successful intravenous tocolysis with magnesium sulfate, 69 women with
      preterm labor at <35 weeks gestation were randomly assigned to nifedipine (20 mg
      orally every 4-6 hr), or diltiazem (30-60 mg orally every 4-6 hr). The primary
      outcome was the percentage of patients achieving 37 weeks gestation. Maternal
      cardiovascular alterations and neonatal outcomes were also assessed. Sixty-nine
      patients were available for final analysis. Less patients on diltiazem as
      compared to nifedipine achieved 37 weeks (15.1% vs. 41.7%, P = 0.019).
      Gestational age at delivery was also less for patients receiving diltiazem (35.5
      +/- 3.5 weeks vs. 33.4 +/- 3.9 weeks, P = 0.022). There were fewer days gained in
      utero from randomization to delivery with diltiazem as compared to nifedipine;
      however, this difference was not statistically significant (22.4 +/- 16.3 days
      vs. 31.2 +/- 24.4 days, P = 0.084). Maternal blood pressure and pulse during
      tocolysis did not differ significantly between groups. Despite the theoretical
      advantages of diltiazem tocolysis, maintenance tocolysis with diltiazem offered
      no benefit over nifedipine in achieving 37 weeks gestation. The cardiovascular
      alterations with either drug in normotensive, pregnant patients appear minimal.

PMID- 9775990
TI  - Ballantyne syndrome: is placental ischemia the etiology?
AB  - Ballantyne syndrome is a condition in which the gravid patient essentially
      "mirrors" the in utero state of the hydropic fetus. The exact pathophysiological
      mechanism, however, is unclear. At 25 weeks gestation, a 28-year-old G3P2
      presented with acute onset lower extremity edema, hyperuricemia, polyhydramnios,
      generalized pruritus, hemodilutional anemia, and pre-term labor. The human
      chorionic gonadotrophin (hCG) level was markedly elevated, at 570,020 mIU/ml.
      Postpartum, she developed a pre-eclampsia-like syndrome with oliguria and
      pulmonary effusions. Associated placental findings included a 8 x 7 x 7 cm
      chorangioma. Underlying placental ischemia, reflected by a hyperproliferative
      trophoblast, increased hCG secretion, and increased placental resistance may
      account for the maternal findings of Ballantyne syndrome.

PMID- 9775991
TI  - Comparison of elective and empiric cerclage and the role of emergency cerclage.
AB  - We describe the maternal, obstetric, and neonatal outcomes of patients undergoing
      elective, empiric, and emergency cervical cerclage at our institution in an
      attempt to determine predictive factors for adverse perinatal and maternal
      outcomes. A retrospective chart review was conducted on patients who underwent
      cervical cerclage placement over a 7-year time span. Of 55 charts, 40 contained
      complete peripartum data satisfactory for review; 7 elective, 15 empiric, and 18
      emergency cerclages were analyzed. There was no perinatal mortality in the
      elective group, and 5/7 patients delivered at term. The empiric population
      experienced a 20% neonatal mortality; 6/15 gestations progressed to term. The
      perinatal mortality was 44% in the emergency group and 2/18 patients delivered at
      term. Relative to neonatal outcome, elective cerclage was statistically
      significantly better than emergent cerclage; there was no statistically
      significant difference between the elective and empiric groups nor between the
      empiric and emergent groups. This relatively small series with a large number of
      variables appeared to favor an elective procedure rather than an empiric one.
      Although emergent cerclage was associated with only a 56% neonatal survival, it
      did have value in some patients.

PMID- 9775989
TI  - Bacteria-induced or bacterial product-induced preterm parturition in mice and
      rabbits is preceded by a significant fall in serum progesterone concentrations.
AB  - Bacterial products are thought to induce labor by stimulating the production of
      pro-inflammatory cytokines and prostaglandins in gestational tissues, leading to
      the onset of preterm parturition. Progesterone withdrawal is a prerequisite of
      parturition in many species. Yet a role for progesterone in the mechanisms
      responsible for preterm parturition, in the setting of infection, is unclear. The
      current studies were conducted to determine if a fall in serum progesterone
      concentrations occurs before the onset of bacterial product-induced preterm
      parturition in animals. Accordingly, pregnant mice at day 15 (70% gestation) were
      injected i.p. with Escherichia coli lipopolysaccharide (LPS; 50 microg/mouse) and
      timed-pregnant rabbits were inoculated transcervically with a suspension of E.
      coli to cause an ascending intrauterine infection. Control animals in both groups
      received equal volumes of sterile phosphate-buffered saline (PBS) solution. Blood
      specimens were collected at regular intervals and serum progesterone levels were
      determined by RIA. Within 14 h of LPS administration, mice delivered their pups.
      The median concentrations of serum progesterone were significantly lower at 1 h,
      4 h, 10 h, and at the onset of preterm parturition (11-12 h) after LPS injection,
      compared to that in animals given PBS. Similarly, E. coli-inoculated rabbits
      delivered 1-2 days posttranscervical inoculation and demonstrated 60% decrease in
      serum progesterone within 12-24 h of inoculation compared to those given PBS.
      Parturition in both control groups occurred at term, following typical
      progesterone withdrawal. It is concluded that LPS administration to pregnant mice
      and ascending intrauterine infection in pregnant rabbits is associated with a
      dramatic fall in serum progesterone concentrations prior to the onset of
      parturition.

PMID- 9775992
TI  - Successful pregnancy following orthotopic liver transplantation for idiopathic
      Budd-Chiari syndrome.
AB  - Budd-Chiari syndrome is a rare and serious thrombotic event with significant
      morbidity and mortality. Recommendations regarding future conception and
      management during pregnancy have not been defined. We present a patient with
      history of idiopathic Budd-Chiari Syndrome and subsequent orthotopic liver
      transplantation who was successfully managed during pregnancy. A 24-year-old
      white female, gravida 1 para 0, status postorthotopic liver transplantation 5
      years previously for Budd-Chiari syndrome with post-transplant insulin-dependent
      diabetes mellitus presented to our clinic at 7 weeks of gestation for initial
      prenatal evaluation. Maintenance immunosuppressive therapy and prophylactic
      heparin anticoagulation was administered throughout the pregnancy, which was
      uneventful until 35 weeks gestation, at which time pre-eclampsia and premature
      preterm rupture of membranes prompted labor induction. The patient developed no
      evidence of acute or chronic hepatic rejection and no evidence of recurrent Budd
      Chiari syndrome during the pregnancy or post-partum convalescence. Prudent use of
      prophylactic anticoagulation, close immunosuppressive monitoring, and periodic
      fetal and maternal surveillance are warranted in patients with previous
      orthotopic liver transplantation for idiopathic Budd-Chiari syndrome and may
      reduce risk of recurrence during pregnancy.

PMID- 9775994
TI  - Relationship between endomyometritis and the duration of premature membrane
      rupture.
AB  - In this study, correlation between duration of premature rupture of the membranes
      (PROM) and the degree of membrane, decidua, and myometrium infections were
      histologically investigated. The study was carried on 61 women with term
      pregnancy (30 with PROM, 31 control group). During cesarean section, a full
      thickness biopsy specimen of the uterine wall from serosa to decidua was obtained
      with scissors. Chorioamnionitis was histopathologically identified by
      neutrophilic leukocyte (NL) infiltration of the membranes. Endometritis or
      myometritis were diagnosed when the acute inflammatory process extended to the
      decidua or the myometrium successively. It was found that the presence and depth
      of NL infiltration significantly correlates with the interval between rupture of
      membranes and termination of pregnancy.

PMID- 9775993
TI  - Lack of relationship between histologic chorioamnionitis and duration of the
      latency period in preterm rupture of membranes.
AB  - It is often believed that the frequency of clinical chorioamnionitis in preterm
      premature rupture of membranes (PROM) increases with the duration of the interval
      between membrane rupture and delivery. We tested the hypothesis that the
      prevalence of histologic evidence of intrauterine infection increases
      proportionally to the duration of the latency period. A total of 191 consecutive
      placentas of singleton, nonanomalous, liveborn infants delivered at <32 weeks'
      gestation with PROM were examined prospectively. Demographic, obstetric,
      histopathologic, and neonatal information was obtained. Histopathologic evidence
      of acute inflammation in choriodecidua, amnion, umbilical cord, and chorionic
      plate was recorded and scored. The prevalence and severity of pathological
      evidence of intrauterine infection was correlated with the interval between
      membrane rupture and delivery. Maternal and neonatal outcomes were assessed in
      six groups defined by different intervals between membrane rupture and delivery.
      Statistical analysis utilized regression, Fisher's exact test, Chi-square, and
      one-way analysis of variance after log transformation where applicable. P < 0.05
      was considered significant. No correlation was observed between total score of
      placental acute inflammation and the interval membrane rupture-to-delivery (r =
      0.068, 95% confidence interval -0.075, 0.211; P = 0.35). There was no evidence
      that the rate of maternal (P = 0.4) or neonatal (P = 0.15) infectious morbidity,
      or the total score of acute placental inflammation (P = 0.13), acute amnionitis
      (P = 0.35), choriodeciduitis (P = 0.46), chorionic plate inflammation (P = 0.38),
      or umbilical and chorionic vasculitis (P = 0.06) increase with the prolongation
      of the PROM-to-delivery interval. This study had an 85% power to detect the lack
      of association that was actually observed. The rate of histologic evidence of
      chorioamnionitis in preterm PROM does not increase with the duration of the PROM
      to-delivery interval.

PMID- 9775995
TI  - Complete trisomy 9 in a term fetus: a case report.
AB  - Complete trisomy 9 was diagnosed in a 35-week fetus by amniocentesis. Several
      sonograms had revealed only a two-vessel cord and intrauterine growth
      restriction. No other abnormalities were noted. A stillborn infant was delivered
      at 37 weeks gestation after induction of labor.

PMID- 9775996
TI  - Hospital readmission for postpartum endometritis.
AB  - This study identified risk factors associated with readmission for postpartum
      endometritis. The study group consisted of 109 mothers (Group I) who were
      discharged after delivery and readmitted with endometritis. Control groups
      consisted of women who had endometritis immediately after delivery but who did
      not require readmission (Group II, n = 109), and women who had no intrapartum or
      puerperal infection and also were not readmitted (Group III, n = 109). Subjects
      in Groups II and III were matched to an index study subject for date of delivery
      and maternal age, race, and parity; and women in Groups I and III were also
      matched for route of delivery. Groups were compared in terms of demographic
      characteristics, intrapartum course, and clinical presentation. The data were
      analyzed with the t-test, chi2, and multiple logistic regression analyses, and a
      P value < .05 was considered significant. Women in Groups I and III delivered
      vaginally more often than mothers in Group II. In addition, mothers in Groups I
      and III had similar postpartum courses, no evidence of infection on discharge
      after delivery, and a similar period from delivery until postpartum discharge.
      Although women in Group I were more likely to have spontaneous rupture of
      membranes, a shorter latent period, and have fewer bilateral tubal ligations than
      mothers in Group II, multivariate analysis identified route of delivery as the
      only significant maternal variable associated with postpartum endometritis
      requiring readmission. Women who were readmitted for endometritis usually
      delivered vaginally, and the occurrence of late-onset postpartum endometritis was
      unrelated to the length of stay following delivery.

PMID- 9775997
TI  - Long-term effects of HIV counseling and testing for women: behavioral and
      psychological consequences are limited at 18 months posttest.
AB  - Behavioral and psychological consequences of HIV counseling and testing (HIV C&T)
      for women were examined in a longitudinal, prospective study. Women who received
      HIV C&T at community health clinics (n = 106) and a comparison group of never
      tested women (n = 54) were interviewed five times over 18 months. There was no
      change in risk behaviors as a consequence of testing: tested and untested women
      engaged in high-risk sexual behavior at baseline and 18 months later. Tested
      women reported more anxiety, depression, and intrusive thoughts about AIDS than
      did untested women. Although tested women were more concerned about AIDS, their
      potential risk factors over the study period generally were equivalent to those
      for untested women. HIV counseling and testing should be considered one aspect of
      a broader program of HIV prevention. Identification of alternative interventions
      must be a public health priority.

PMID- 9775998
TI  - HIV sexual risk behavior following bereavement in gay men.
AB  - The present study followed a group of 100 gay men up to 1 year before and 1 year
      after losing a partner to AIDS (University of California, San Francisco Coping
      Project). Following bereavement, participants were at increased risk for engaging
      in unprotected anal intercourse: at 4 to 6 months for HIV-negative men and at 8
      to 12 months for HIV-positive men. Sociodemographic variables, HIV serostatus,
      substance use, depression, prebereavement relationship quality, and social
      support did not explain sexual risk-taking in this sample. However, men who
      engaged in unprotected anal intercourse were twice as likely to be involved in a
      new primary relationship as those who did not. The authors concluded that risk
      varies over time by HIV status and may involve engagement in new relationships.

PMID- 9775999
TI  - Psychological predictors of good health in three longitudinal samples of educated
      midlife women.
AB  - Concurrent and longitudinal associations between cognitive and affective
      personality variables--intellectual efficiency (IE), anxiety, and hostility--and
      observer ratings of physical health were examined in 3 longitudinal samples of
      women: Mills Longitudinal Study (n = 101); Radcliffe Study (RS, n = 118); and
      University of California, San Francisco Study (n = 44). Observer ratings of
      health were based on participants' reports of health problems. The California
      Psychological Inventory (H. G. Gough, 1996) IE, Hostility, and Anxiety Scales
      were used in all studies at Times 1 and 2, except in RS, when at Time 1 the Zung
      Anxiety (W. K. Zung, 1971) and the Profile of Mood States (D. M. McNair, M. Lorr,
      & L. F. Droppleman, 1971) Hostility Scales were used. In the majority of
      analyses, IE was positively associated with good health, and Anxiety and
      Hostility were negatively associated with health. IE was the strongest
      independent predictor of health, indicating that cognitive characteristics may
      have an important role in health and should be examined further.

PMID- 9776000
TI  - Transition to chronic pain in men with low back pain: predictive relationships
      among pain intensity, disability, and depressive symptoms.
AB  - Pain intensity, disability, and depressive symptoms are hallmarks of chronic pain
      conditions, but little is known about the relationships among these symptoms in
      the transition from acute to chronic pain. In this study, an inception cohort of
      men with low back pain (N = 78) was assessed at 2, 6, and 12 months after pain
      onset. At 6 months, pain intensity, disability, and depressive symptoms were
      predicted only by their respective levels at 2 months after pain onset. At 12
      months, pain intensity and depressive symptoms were predicted by heightened
      disability at 6 months after pain onset; 12-month depressive symptoms also were
      predicted by 2-month disability. Pain intensity was not predictive of changes in
      disability or depressive symptoms. These findings suggest that functional
      disability plays a more prominent role than pain intensity in the transition from
      acute to chronic pain. A "failure to adapt" conceptual model is presented to
      account for these results.

PMID- 9776001
TI  - Responses of natural killer cell activity to acute laboratory stressors in
      healthy men at different times of day.
AB  - To assess possible diurnal variations in natural killer reactivity to acute
      laboratory stressors, this study investigated changes in natural killer cell
      activity (NKCA) during and after three stressors (mental arithmetic, speech, and
      the Stroop) at 3 times of the day (08:00, 12:00, and 16:00) in 30 healthy men.
      NKCA activity increased during mental arithmetic and speech tasks at all 3 times
      of the day. Change in NKCA was greatest in the afternoon. Differences in the
      magnitude of mood changes were also observed at the 3 times of day, parallel to
      immune reactivity. These findings suggest that the dynamics of stress-related
      NKCA are more complex than previously believed and that time of day may affect
      the way they are generated or interpreted.

PMID- 9776002
TI  - Effects of video-relayed social support on hemodynamic reactivity and salivary
      cortisol during laboratory-based behavioral challenge.
AB  - The authors tested the effects of a laboratory analogue of social support on
      reactivity to laboratory-based behavioral challenge. Video-relayed supportive
      commentary was provided by a same-sex confederate while participants (40 healthy
      men and women assigned to support and no-support groups) performed a demanding
      computer task, and their heart rate, systolic and diastolic blood pressure, and
      salivary cortisol were measured. The authors found that heart rate and cortisol
      level (but not blood pressure) were attenuated in the support condition for both
      genders. Objective performance on the task was similar in both groups, but the
      social support group reported higher levels of perceived support and rated the
      task as easier than did participants in the no-support condition. Video
      presentation offers new opportunities for systematically examining social support
      and its effects.

PMID- 9776003
TI  - Experimental evidence for stages of health behavior change: the precaution
      adoption process model applied to home radon testing.
AB  - Hypotheses generated by the precaution adoption process model, a stage model of
      health behavior, were tested in the context of home radon testing. The specific
      idea tested was that the barriers impeding progress toward protective action
      change from stage to stage. An intervention describing a high risk of radon
      problems in study area homes was designed to encourage homeowners in the model's
      undecided stage to decide to test, and a low-effort, how-to-test intervention was
      designed to encourage homeowners in the decided-to-act stage to order test kits.
      Interventions were delivered in a factorial design that created conditions
      matched or mismatched to the recipient's stage (N = 1,897). Both movement to a
      stage closer to testing and purchase of radon test kits were assessed. As
      predicted, the risk treatment was relatively more effective in getting undecided
      people to decide to test than in getting decided-to-act people to order a test.
      Also supporting predictions, the low-effort intervention proved relatively more
      effective in getting decided-to-act people to order tests than in getting
      undecided people to decide to test.

PMID- 9776004
TI  - The relationship between smoking and body weight in a population of young
      military personnel.
AB  - Evidence indicates that middle-aged smokers weigh less than nonsmokers and that
      smoking cessation reliably produces weight gain, but recent studies have
      questioned the weight control "benefits" of smoking in younger populations (the
      time that people typically initiate smoking). The relationship between smoking
      and body weight was evaluated in all U.S. Air Force Basic Military Training
      recruits during a 1-year period (n = 32,144). Those who smoked prior to Basic
      Military Training (n = 10,440) were compared to never smokers or experimental
      smokers. Results indicated that regular-current smoking had no relationship to
      body weight in women (p > .05) and a very small effect in men (p < .05).
      Ethnicity, education, income, and duration and intensity of smoking did not
      affect the relationship between smoking and body weight. It was concluded that
      smoking has no effects on the body weights of young women and minimal effects in
      young men.

PMID- 9776005
TI  - Trait anxiety, symptom perceptions, and illness-related responses among women
      with breast cancer in remission during a tamoxifen clinical trial.
AB  - Postmenopausal women with breast cancer in remission (N = 140) who were
      participating in a randomized clinical trial of tamoxifen chemoprevention therapy
      completed measures of trait anxiety, symptoms, cancer worry, and breast self
      examinations (BSEs) during the first 6 months of the trial. Trait anxiety was
      associated with heightened sensitivity to tamoxifen-induced symptoms (but not
      with tendencies to report increases in symptoms unrelated to tamoxifen use),
      greater tendencies to attribute symptoms to tamoxifen use, and greater cancer
      worry. Tamoxifen use increased BSE rates among high-anxiety participants. For low
      anxiety participants, tamoxifen use increased cancer worry but not BSE rates.
      Trait anxiety appears to be associated with vigilant activation of illness
      related representations that trigger attentiveness to sensations, worry, and
      protective coping in response to somatic cues.

PMID- 9776006
TI  - Number of pregnancies, outcome expectancies, and social norms among HIV-infected
      young women.
AB  - In this descriptive study, researchers examined pregnancies, sexually transmitted
      diseases (STDs), and sexual behaviors among 67 HIV-infected young women, as well
      as the women's outcome expectancies and peer and partner norms regarding
      pregnancy. Many of the women (69%) had been pregnant; 42% had been pregnant at
      least once since learning their HIV status, with 71% choosing to carry to term,
      resulting in 25% (N = 5) of the babies infected. The women had positive outcome
      expectancies related to pregnancy, which were significantly correlated with peer
      and partner social norms. Lack of knowledge regarding infant transmission, high
      rates of STDs, and inconsistent condom use all indicate a need for improved
      intervention regarding pregnancy and decision-making. Suggestions for better
      methods of providing information to HIV+ young women are provided.

PMID- 9776008
TI  - Medical identification numbers: a good idea that won't work...yet.

PMID- 9776007
TI  - Coronary Artery Smoking Intervention Study (CASIS): 5-year follow-up.
AB  - The authors compared the effect of a behavioral multicomponent smoking cessation
      special intervention (SI) to an advice-only intervention (AO) on smoking status
      at 5 years for smokers with coronary disease (n = 160). Regression analyses
      revealed an interaction between intervention type and disease severity such that
      patients in the SI group with greater degrees of coronary artery disease showed
      significantly higher cessation rates (odds ratio = 344 for 3-vessel disease in
      the SI vs. AO, p = .01). Factors predicting maintained abstinence included having
      12 or more years of education, contemplating quitting smoking or being ready to
      begin action to quit at baseline, and having a higher self-efficacy score.

PMID- 9776009
TI  - Nocturia in adults: etiology and classification.
AB  - Nocturia is one of the most bothersome of all urologic symptoms, yet even a
      rudimentary classification does not exist. We herein propose a classification
      system of nocturia based on a retrospective study. The records of 200 consecutive
      patients with nocturia were reviewed. Evaluation included history, micturition
      diary (including day, night, and 24-hr voided volume), postvoid residual urine
      (PVR), and videourodynamic study (VUDS). Functional bladder capacity (FBC) was
      determined to be the largest voided volume in a 24-hr period. The etiology of
      nocturia was thus classified into one of three groups: nocturnal polyuria ([NP]
      in which voided urine volume during the hours of sleep exceeds 35% of the 24-hr
      output), nocturnal detrusor overactivity ([NDO] defined as nocturia attributable
      to diminished bladder capacity during the hours of sleep), and mixed (NP+NDO);
      polyuria (24-hr urine output >2,500 cc) was classified separately. There were 129
      women and 65 men ranging in age from 17 to 94 years (x=59). Overall 13 (7%) had
      NP, 111 (57%) NDO, and 70 (36%) had a mixed etiology of their nocturia (both NP
      and NDO). Forty-five (23%) also had polyuria. These data confirm that the
      etiology of nocturia is multifactorial and in many instances unrelated to the
      underlying urologic condition. Nocturnal overproduction of urine is a significant
      component of nocturia in 43% of patients, most of whom will also have NDO. We
      believe that treatment should be directed at both conditions.

PMID- 9776010
TI  - Different voiding dynamics in stable and unstable bladders with and without
      outlet obstruction.
AB  - Of 120 men with benign prostatic enlargement who were evaluated urodynamically,
      60 had stable bladders, with (n=30) and without (n=30) outlet obstruction (OO),
      whereas 60, both obstructed (n=30) and unobstructed (n=30), had detrusor
      instability (DI). The unstable bladders, wither in the absence or presence of OO,
      always showed a greater mechanical capability. In particular, compared to the
      stable bladders, the unstable ones not only had greater strength, but also showed
      a higher maximum shortening velocity (as well as a shorter opening time and not
      significantly higher internal work). In the obstructed unstable series, compared
      to the obstructed stable one, such findings paralleled a more severely increased
      urethral impedance, which suggests that a functional "compensatory" response to a
      greater OO was facilitated. All such data were hypothesized to result from
      microstructural changes yielding an easier electrical coupling between the
      detrusor smooth muscle cells and hence both a state of DI and better synchronized
      (thus, stronger and faster) micturition contractions. At least, the latter would
      be the case should there be no heavy bladder collagenosis upsetting the spread of
      the depolarization wave.

PMID- 9776011
TI  - Urinary bladder bilharziasis as a cause of impaired bladder muscle contractility.
AB  - In an attempt to evaluate the effect of bilharziasis on bladder contractility as
      a factor in the genesis of voiding disorders, 44 cases of bilharzial bladder neck
      obstruction diagnosed using traditional methods (symptomatological, radiographic,
      and endoscopic) were subjected to complete urodynamic evaluation (flowmetry,
      cystometry, pressure/flow study, and stop-flow test). Their parameters were
      compared with those of 28 patients with urodynamically obstructed benign
      prostatic hyperplasia and 8 nonsymptomatic controls. Contractility parameters
      (isometric detrusor pressure, maximum estimated flow rate, detrusor power at
      maximum flow) were calculated for the studied cases and their distribution
      according to the Schafer pressure/flow diagram was evaluated. Bladder biopsy
      including the detrusor was evaluated in all 72 patients. Poor bladder
      contractility associated with an extensive bilharzial effect on the detrusor
      muscle was found to be the major abnormality in 20 of 44 patients with presumed
      bilharzial bladder neck obstruction with no evidence of urodynamic outflow
      obstruction. We believe such a workup is essential in cases of suspected
      obstruction associated with bilharziasis to throw light on the pathophysiology of
      the voiding disorders, avoid unnecessary surgery, and provide a better prognosis.

PMID- 9776012
TI  - Urodynamic findings in postprostatectomy incontinence.
AB  - Due to the large variability in the reported contribution of bladder dysfunction
      to postprostatectomy incontinence and the impact this dysfunction may have on the
      outcome of selected treatment, we retrospectively reviewed the videourodynamic
      findings of bladder and sphincteric function in patients with postprostatectomy
      incontinence. The contributions of bladder and sphincteric causes of incontinence
      are determined. Ninety-two patients had multichannel videourdynamic testing
      performed as part of a comprehensive evaluation for incontinence at least 1 year
      after prostatectomy. Using a 6-French double-lumen catheter in the bladder and a
      10-French catheter in the rectum, all pressures were recorded continuously while
      in the upright position. Valsalva leak point pressures (VLPP) were measured in
      the absence of a bladder contraction at a 150-ml volume and at 50-ml increments
      thereafter until maximum functional capacity was reached. Bladder compliance and
      bladder capacity were determined and the presence of detrusor instability (DI)
      was documented. Sixty-five patients (71%) presented after radical prostatectomy
      (RP) and 27 patients (29%) after transurethral resection of the prostate (TURP).
      The predominant urodynamic finding was sphincteric incompetence as VLPP were
      obtained in 85 patients (92%) and ranged from 12 to 120 cm water. DI was a common
      finding, occurring in 34 patients (37%), and classified as follows: a) phasic
      instability in 22/34, b) tonic instability in 3/34, and c) mixed phasic and tonic
      instability in 9/34. However, we found DI to be the sole cause of incontinence in
      only 3/92 patients (3.3%). There was no statistically significant difference in
      the incidence of sphincteric incompetence after RP or TURP; however, TURP
      patients had a higher incidence of DI, which was statistically significant
      (P=0.019). There was no correlation of incontinence severity and VLPP when
      comparing preoperative pad usage to VLPP < or =70 or > or =71 cm water. Although
      bladder dysfunction may be contributing problem in patients with
      postprostatectomy incontinence, it is rarely the only mechanism for this
      disorder. VLPP does not correlate with incontinence severity. Although
      sphincteric incompetence is the most common mechanism contributing to
      incontinence after prostatectomy, bladder dysfunction may coexist or be an
      isolated cause of postprostatectomy incontinence. Therefore, urodynamic studies
      are important to illustrate the exact cause(s) of incontinence in each individual
      patient after prostatectomy.

PMID- 9776013
TI  - Dose-ranging study of tolterodine in patients with detrusor hyperreflexia.
AB  - Tolterodine is a potent antimuscarinic agent specifically developed for the
      treatment of urinary urge incontinence and other symptoms related to the
      overactive bladder. In order to assess the optimum dosage for use in future
      clinical studies, a double-blind, randomized, placebo-controlled, parallel-group,
      multicenter study was performed in 90 patients with detrusor hyperreflexia and
      symptoms of urinary urgency, frequency, and/or urge incontinence. Urodynamic
      variables, micturition diary variables, and subjective urinary symptoms were
      measured before and after 2 weeks' treatment with either placebo or tolterodine
      0.5, 1, 2, or 4 mg twice daily (bd). Serum drug concentrations, electrocardiogram
      recordings, blood pressure, and incidence of adverse events were also assessed.
      Linear regression analysis showed a significant dose-response relationship for
      several clinically relevant urodynamic variables, while there was a trend towards
      an improvement in micturition diary variables and subjective assessment of
      symptoms with increasing dosages of tolterodine. There were no safety or
      tolerability concerns regarding any of the dosages of tolterodine investigated,
      although 2 patients treated with a dosage of 4 mg bd experienced urinary
      retention that necessitated dosage reduction. The results of this study suggest
      that tolterodine is well-tolerated and exerts a dose-dependent effect on bladder
      function in patients with detrusor hyperreflexia. The optimum dosage of
      tolterodine for use in future studies is 1-2 mg bd.

PMID- 9776014
TI  - Capsaicin and neurogenic detrusor hyperreflexia: a double-blind placebo
      controlled study in 20 patients with spinal cord lesions.
AB  - The aim of this study was to investigate the efficacy and tolerance of capsaicin,
      a neurotoxin for C-fiber afferents, applied intravesically in the treatment of
      detrusor hyperreflexia. Eleven male and nine female patients who had spinal cord
      lesions caused by multiple sclerosis (12) or trauma (eight) resulting in detrusor
      hyperreflexia with urge incontinence and pollakiuria were randomized to receive
      one intravesical instillation of either 30 mg capsaicin in 100 ml 30% ethanol or
      100 ml 30% ethanol alone. The patients were evaluated clinically (voiding diary)
      and urodynamically (maximum cystometric capacity, maximum detrusor pressure,
      first and normal desire to void) before and 30 days after the instillation. On
      day 30, the 10 patients who received capsaicin had significant decreases in 24-h
      voiding frequency from 9.3+/-6.1 to 6.7+/-3.8 (P=0.016) and leakages from 3.9+/
      1.6 to 0.6+/-0.8 (P=0.0008); their maximum cystometric capacity increased from
      169+/-68 to 299+/-96 ml (P=0.01) and maximum detrusor pressure decreased from
      77+/-24 to 53+/-27 cm H2O. There were no significant changes in the control
      group. In seven subjects in each group, instillation triggered immediate side
      effects (suprapubic pain, sensory urgency, flushes, hematuria, autonomic
      hyperreflexia) that resolved within 2 weeks. Intravesical capsaicin significantly
      improves clinical and urodynamic parameters of detrusor hyperreflexia in spinal
      cord-injured patients. Side effects are frequent, tolerable, and identical to
      those induced by 30% ethanol alone.

PMID- 9776015
TI  - Bladder tissue biopsies in spinal cord injured patients: histopathologic aspects
      of 61 cases.
AB  - It was the aim of this histopathologic study to examine and compare results of
      bladder tissue biopsies in spinal cord injured (SCI) patients. The study group
      consisted of 61 SCI patients who received treatment at the Swiss Paraplegic
      Centre in Nottwil, near Lucerne, Switzerland. The mean age of the study group was
      41 years (range, 17-73) and the mean duration of spinal cord lesion was 10 years
      and 4 months (range, 5 months to 44 years). The male:female ratio was 57:4.
      Bladder infections had occurred in each patient one to six times per year
      (median, 3.2). All samples were taken from the trigone of the bladder during
      endoscopic urologic procedures with a flexible cystoscope. Histopathologic
      analysis showed abnormal alterations of bladder tissue in 56 SCI patients
      (91.8%). Forty-six SCI patients (75.4%) had a chronic type and 10 SCI patients
      (16.4%) a subacute type of inflammation. Normal bladder tissue was found in five
      cases (8.2%). Further observation revealed the presence of fibrosis (34.4%),
      edema (9.8%), and lymphoid hyperplasia (6.6%). A t-test for independent samples
      showed a lack of significant correlation between the number of clinical bladder
      infections per year, the duration of injury, the neurologic level of the spinal
      cord lesion, and histopathologic types of infections.

PMID- 9776016
TI  - Urethral sphincter needle electromyography in women: comparison of periurethral
      and transvaginal approaches.
AB  - Needle electromyography (EMG) of the striated urethral sphincter is the only
      technique that permits detection of individual motor unit action potentials
      (MUAPs) and is a valuable diagnostic tool in the evaluation of women with urinary
      incontinence and voiding disorders. The purpose of this study was to compare two
      methods of urethral needle EMG with respect to the number of MUAPs identified,
      the amount of patient discomfort, and the duration of the examination. Twenty
      consecutive women referred for electrodiagnostic testing to evaluate symptoms of
      urinary incontinence and/or voiding dysfunction underwent both methods of the
      needle examination in a prospective randomized cross-over study design with each
      patient acting as her own control. A full cross-over analysis was conducted to
      detect period and sequence effects using analysis of variance with a power of
      0.85 and a significance level of P < 0.05. Twice as many MUAPs were identified
      using the periurethral approach (8.8 versus 3.9) with a mean difference of 5.0
      (P=0.0008). There was a non-significant trend to greater patient discomfort with
      the periurethral approach; however, the discomfort was generally rated as mild to
      moderate. The length of time required to count all identifiable MUAPs did not
      vary significantly between the two methods. We conclude that the periurethral
      approach is superior to the transvaginal approach with respect to the quantity of
      electrodiagnostic information obtained and propose that this method be
      standardized to characterize more accurately the neurogenic component of urinary
      incontinence and voiding dysfunction for future electrodiagnostic studies.

PMID- 9776017
TI  - Clinical assessment of pelvic floor dysfunction in multiple sclerosis: urodynamic
      and neurological correlates.
AB  - We present a study on the clinical assessment of pelvic floor dysfunction in 30
      female patients with proven multiple sclerosis (MS). A scoring system for pelvic
      floor muscle testing by digital vaginal palpation is proposed. The concept of
      pelvic floor spasticity in MS is introduced. The relationship of our findings
      with the neurological findings and urodynamic data is presented. Pelvic floor
      spasticity correlates well with the presence of detrusor-external sphincter
      dyssynergia and with more severe spinal cord disease.

PMID- 9776018
TI  - Modulation of the micturition reflex pathway by intravesical electrical
      stimulation: an experimental study in the rat.
AB  - Intravesical electrical stimulation (IVES) is used clinically to improve bladder
      evacuation in patients with inadequate micturition contractions. The procedure
      involves field stimulation of Adelta bladder mechanoreceptor afferents resulting
      in a prolonged enhancement of the micturition reflex. The aim of the present
      experimental study in the rat was to identify the site for this neuromodulation,
      whether it was due to sensitization of bladder mechanoreceptors, to enhancement
      of transmission in the central micturition reflex pathway, or to improved
      effectiveness of the peripheral motor system of the bladder. The experiments were
      performed on female rats, anesthetized by alpha-chloralose. Multi-unit afferent
      or efferent activity was recorded from bladder pelvic nerve branches during
      repeated cystometries before and after IVES. The specific antagonist CPPene was
      used to block central glutaminergic receptors of NMDA type. Micturition threshold
      volume decreased significantly after IVES. The afferent threshold volume, peak
      response, and pressure sensitivity were unchanged as were the peak efferent
      activity and bladder contractility. There was no efferent activity until just
      before the micturition contraction. The IVES-induced decrease in micturition
      threshold was blocked by prior administration of the NMDA (N-methyl-D-aspartic
      acid) antagonist CPPene (3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphonic
      acid). The findings indicate that the IVES-induced modulation of the micturition
      reflex is due to an enhanced excitatory synaptic transmission in the central
      micturition reflex pathway. The observed modulation may account for the clinical
      beneficial effect of IVES treatment.

PMID- 9776019
TI  - Urodynamic parameters in scrapie-affected ewes and their modifications in the
      course of the disease.
AB  - The aim of this study was to determine the urological abnormalities linked to
      spontaneous spongiform encephalopathy and their occurrence in the course of the
      disease. The animals used in this were 11 healthy and 20 scrapie-affected ewes.
      The scrapie-affected ewes were studied at a rate of once a month (1 to 5
      measures; mean, 2.55) until they died. Urodynamic explorations were performed.
      The bladder activity was explored using cystometry. The urethral activity was
      measured during cystometry and during a urethral pressure profile. Both were
      analyzed using International Continence Society recommendations. Results showed
      in scrapie-affected ewes a decrease in functional bladder capacity and an
      increase in detrusor contraction incidence during filling of the bladder and in
      the occurrence of significant urethral instability. Bladder abnormalities were
      seen only in scrapie-affected ewes and worsened during the course of the disease.
      Urethral instability was not typical of the disease but was significantly more
      frequent in scrapie-affected ewes. It was concluded that lower urinary tract
      dysfunction occurred in scrapie-affected ewes and worsened during the course of
      the disease. This dysfunction is in agreement with overactive detrusor function
      due to neurological lesions.

PMID- 9776020
TI  - "When you build it, keep it simple": comment on "If you build it, they will come"
      (1998): Neurourol Urodynam 17:1-2.

PMID- 9776021
TI  - Recording the detrusor electromyogram is still a difficult and controversial
      enterprise.

PMID- 9776022
TI  - The relationship of dental calculus to caries, gingivitis, and selected salivary
      factors in 11- to 13-year-old children in Chiang Mai, Thailand.
AB  - Thai children have been shown to accumulate large amounts of dental calculus. The
      purpose of this study was to examine the relationship of calculus to caries and
      gingivitis, and salivary conditions which may contribute to calculus
      accumulation. Four-hundred and thirty-nine (439) children from 18 schools in
      Chiang Mai were selected for this study. The children were given oral
      examinations to determine calculus index (CI); decayed, missing, and filled
      surfaces (DMFS); decayed, missing, and filled teeth (DMFT); gingival index (GI);
      and plaque index (PI). Children with mean CI scores > or =1 (206) were assigned
      to the calculus group; the 233 children with mean CI scores of <1 to the
      noncalculus group. Saliva was collected from 60 randomly-selected children in
      each group. Unstimulated and stimulated whole saliva and stimulated parotid
      saliva were assessed for flow rate, pH, and buffer capacity using 2 methods.
      Results showed that calculus status was not significantly associated with caries,
      but that there was a high association between gingivitis and plaque status with
      calculus accumulation (P < 0.001). There were no significant differences in
      saliva flow rate, pH, or buffer capacity between calculus and noncalculus groups.
      The lack of association between calculus status and caries indicated these 2
      conditions have different etiologies and suggests the importance of plaque and
      calculus prevention programs, in addition to caries control efforts, to maintain
      oral health of Thai children.

PMID- 9776023
TI  - Periodontal findings in elderly patients with non-insulin dependent diabetes
      mellitus.
AB  - The periodontal status of 25 patients with non-insulin dependent diabetes
      mellitus (NIDDM) (age range 58 to 76) was investigated and compared with 40 non
      diabetic control subjects (age range 59 to 77). Surfaces with visible plaque and
      bleeding after probing, calculus, recessions, and pathological pockets were
      examined. The total attachment loss was calculated as a sum of recessions and
      pockets in millimeters. Mesial and distal bone loss was measured from panoramic
      radiographs and mean alveolar bone loss was calculated. Periodontal disease was
      considered advanced when mean alveolar bone loss was over 50%, or 2 or more teeth
      had pockets > or = 6 mm. Microbiological analysis comprised the detection of
      Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Bacteroides
      forsythus by a polymerase chain reaction (PCR) method. Patients with NIDDM had
      significantly more often advanced periodontitis than control subjects, 40.0% and
      12.5%, respectively. Diabetic patients did not harbor more pathogens than the
      control subjects. The HbA1C level deteriorated in patients with advanced
      periodontitis, but not in other patients with NIDDM, when compared to the
      situation 2 to 3 years earlier. Advanced periodontitis seems to be associated
      with the impairment of the metabolic control in patients with NIDDM, and a
      regular periodontal surveillance is therefore necessary.

PMID- 9776024
TI  - Computer-assisted densitometric image analysis of digital subtraction images: in
      vivo error of the method and effect of thresholding.
AB  - The aim of the present study was to assess the in vivo error of the method as
      well as the effect of thresholding when obtaining and evaluating standardized
      periapical radiographs for computer-assisted densitometric image analysis
      (CADIA). Twenty healthy volunteers participated in an experimental gingivitis
      study in which neither mechanical nor chemical plaque control was performed for
      21 days. Two pairs of standardized periapical radiographs were taken at days 0
      (baseline) and 21 (follow-up), one from a maxillary area (15 volunteers) and one
      from a mandibular molar/premolar area (17 volunteers). Each baseline radiograph
      was digitized and its image displayed on a monitor. The follow-up radiograph was
      then superimposed and digitized as well. After gray level correction, subtraction
      radiographic images were produced. The difference in gray level between the
      baseline and the follow-up image was calculated within each region of interest
      (ROI) at each picture point (pixel). In bone ROI, changes in density reflected
      the amount of change due to methodological errors plus the basic bone remodeling
      over 3 weeks. For gingival ROI, changes in density reflected the methodological
      error plus a possible change in soft tissue density during the experimental
      gingivitis. Within all of the ROI, some pixels indicated a change in gray level.
      A change in gray level was then thresholded; i.e., only changes >5 and then >10
      gray levels were registered and used for calculation of the CADIA values. With a
      threshold of 5, 44/45 maxillary bone ROI and 60/66 mandibular bone ROI showed a
      change in density, while 41/45 maxillary gingiva ROI and 26/66 mandibular gingiva
      ROI indicated a change in density. With a threshold of 10, 16/45 maxillary bone
      ROI and 12/66 mandibular bone ROI indicated a change in density, while 13/45
      maxillary gingiva ROI and 1/66 mandibular gingiva ROI indicated a change. The
      amounts of changes in density calculated in the various ROI were low even when
      applying no threshold, ranging from -0.279 to 0.621. Applying a threshold of 5,
      the CADIA values ranged from -0.234 to 0.727. With a threshold of 10, the changes
      in density ranged from -0.318 to 0.133. In vivo, CADIA of standardized
      radiographs indicated change in density due to methodological errors. Application
      of thresholds may avoid false-positive diagnoses. When applying CADIA in clinical
      research, the range of change to be expected due to methodological limitations as
      well as the threshold for true change should be evaluated. These thresholds may
      differ in various areas of the mouth, i.e., bone or gingival,
      maxillary/mandibular, anterior/posterior ROI.

PMID- 9776025
TI  - A 2-year clinical evaluation of a diphenylphosphorylazide-cross-linked collagen
      membrane for the treatment of buccal gingival recession.
AB  - To retard collagen membrane enzymatic degradation and to increase its mechanical
      strength, the diphenylphosphorylazide (DPPA) technique has been demonstrated to
      achieve natural cross-links between peptide chains of collagen without leaving
      any foreign product in the cross-linked molecule. In the present prospective
      clinical trial, the potential of a DPPA-cross-linked type I bovine collagen
      membrane was evaluated in the healing of 15 buccal soft tissue recessions in 15
      patients according to the biological concept of guided tissue regeneration. The
      recession decreased from 3.7 mm (SD 1.4) at baseline to 0.8 mm (SD 1.2) at 2
      years postsurgery, corresponding to a mean root coverage of 82.2% (P <0.0001).
      Concurrently, the clinical attachment level decreased from 5.4 mm (SD 1.6) at
      baseline to 1.9 mm (SD 1.2) 2 years postsurgery, corresponding to an average
      clinical attachment gain of 3.5 mm (SD 1.3) (P <0.0001). The 2-year postsurgical
      width of the keratinized tissue was not significantly different from baseline
      values. More than half (53%) of the treated sites showed complete root coverage
      and about two-thirds (73%) of the total cases showed a 75% to 100% disappearance
      of the mucogingival defect. The present investigation demonstrated that the use
      of DPPA-cross-linked collagen membranes in the treatment of human buccal soft
      tissue recessions results in predictable amounts of root coverage and clinical
      attachment gain. Long-term randomization controlled clinical trials of this
      material are needed to fully evaluate its potential for treating periodontal
      recession.

PMID- 9776026
TI  - Effect of a calcium sulfate implant with calcium sulfate barrier on periodontal
      healing in 3-wall intrabony defects in dogs.
AB  - This controlled, split-mouth, preclinical study was designed to evaluate outcome
      following surgical implantation of an allogeneic, freeze-dried demineralized bone
      matrix-calcium sulfate (DBM+CS) composite with a CS barrier in 3-wall intrabony
      periodontal defects in 4 dogs. Control conditions included surgical implantation
      of DBM or CS and gingival flap surgery (GFS) alone. Three-wall intrabony defects
      (4x4x4 mm) were surgically created at the mesial and distal aspect of the
      maxillary and mandibular first and third premolars, respectively. Maxillary and
      mandibular defects each received 1 of the 4 experimental conditions. Experimental
      conditions were rotated between defect sites in subsequent animals. Block
      sections of the defects were collected at sacrifice 8 weeks postsurgery and
      processed for histometric analysis. Histometric defect height (means +/- SD) for
      the DBM+CS, DBM, CS, and GFS groups amounted to 4.2 +/- 0.5, 4.3 +/- 0.7, 4.0 +/-
      0.2, and 4.1 +/- 0.2 mm, respectively. Connective tissue adhesion (connective
      tissue contact to the root without apparent cementum formation) amounted to 0.4
      +/- 0.3, 0.4 +/- 0.3, 0.5 +/- 0.2, and 1.6 +/- 0.5 mm for the DBM+CS, DBM, CS,
      and GFS groups, respectively; the DBM+CS, DBM, and CS groups being significantly
      different from the GFS group (P < 0.05). Cementum regeneration amounted to 3.0 +/
      0.3, 3.1 +/- 0.4, 2.5 +/- 0.4, and 1.6 +/- 0.3 mm for the DBM+CS, DBM, CS, and
      GFS groups, respectively; the DBM+CS, DBM, and CS groups being significantly
      different from the GFS group (P < 0.05). Alveolar bone regeneration amounted to
      2.7 +/- 0.4, 2.7 +/- 0.3, 1.8 +/- 0.5, and 0.7 +/- 0.1 mm for the DBM+CS, DBM,
      CS, and GFS groups, respectively; the DBM+CS, DBM, and CS groups being different
      from the GFS group (P < 0.05), and the DBM+CS and DBM groups being different from
      the CS group (P < 0.05). None of the DBM-containing implants provided evidence of
      bone metabolic activity. In summary, surgical implantation of DBM and CS, alone
      or in combination, may result in significantly improved regeneration of alveolar
      bone and cementum in this preclinical model. Observed regeneration is likely
      unrelated to a biologic activity inherent in DBM. Rather it appears that space
      providing properties of the implants supported observed regeneration.

PMID- 9776027
TI  - Adjunctive use of a subgingival controlled-release chlorhexidine chip reduces
      probing depth and improves attachment level compared with scaling and root
      planing alone.
AB  - The present studies evaluated the efficacy of a controlled-release biodegradable
      chlorhexidine (CHX) (2.5 mg) chip when used as an adjunct to scaling and root
      planing on reducing probing depth (PD) and improving clinical attachment level
      (CAL) in adult periodontitis. Two double-blind, randomized, placebo-controlled
      multi-center clinical trials (5 centers each) were conducted; pooled data are
      reported from all 10 centers (447 patients). At baseline, following 1 hour of
      scaling and root planing (SRP) in patients free of supragingival calculus, the
      chip was placed in target sites with PD 5 to 8 mm which bled on probing. Chip
      placement was repeated at 3 and/or 6 months if PD remained > or = 5 mm. Study
      sites in active chip subjects received either CHX chip plus SRP or SRP alone (to
      maintain study blind). Sites in placebo chip subjects received either placebo
      chip plus SRP or SRP alone. Examinations were performed at baseline; 7 days; 6
      weeks; and 3, 6, and 9 months. At 9 months significant reductions from baseline
      favoring the chlorhexidine chip compared with both control treatments were
      observed with respect to PD (chlorhexidine chip plus SRP, 0.95 +/- 0.05 mm; SRP
      alone, 0.65 +/- 0.05 mm, P < 0.001; placebo chip plus SRP, 0.69 +/- 0.05 mm, P <
      0.001) and CAL (chlorhexidine chip plus SRP, 0.75 +/- 0.06 mm; SRP alone, 0.58 +/
      0.06 mm, P < 0.05; placebo chip plus SRP, 0.55 +/- 0.06 mm, P < 0.05). The
      proportion of patients who evidenced a PD reduction from baseline of 2 mm or more
      at 9 months was significantly greater in the chlorhexidine chip group (19%)
      compared with SRP controls (8%) (P < 0.05). Adverse effects were minor and
      transient toothache, including pain, tenderness, aching, throbbing, soreness,
      discomfort, or sensitivity was the only adverse effect that was higher in the
      chlorhexidine group as compared to placebo (P = 0.042). These data demonstrate
      that the adjunctive use of the chlorhexidine chip results in a significant
      reduction of PD when compared with both SRP alone or the adjunctive use of a
      placebo chip. These multi-center randomized control trials suggest that the
      chlorhexidine chip is a safe and effective adjunctive chemotherapy for the
      treatment of adult periodontitis.

PMID- 9776029
TI  - The response of periodontal ligament cells to fibronectin.
AB  - Fibronectin (fn) is an extracellular matrix (ECM) molecule important in cell
      adhesion and migration and in wound healing. It is also likely important in
      periodontal ligament (PDL) cell-ECM interactions, and thus in regenerating
      periodontal tissues. In this study we characterized PDL cells and their
      interactions with FN, testing different PDL cell isolates taken from healthy and
      diseased conditions. PDL cells were characterized by their morphology, integrin
      profile, motility, and bone nodule formation. Cells were then assayed for
      adhesion, proliferation, and chemotaxis in response to FN or FN fragments. Cell
      isolates were morphologically heterogeneous and fibroblastic, had a normal
      appearing actin cytoskeleton and a wide range of migration potentials, and formed
      bone-like nodules in vitro. They expressed alpha5, beta1, alpha v, and alpha4
      integrin subunits, known receptors for FN, and in fact they bound FN
      preferentially at 5 and 10 microg/ml. Intact FN induced greater PDL cell
      proliferation and chemotaxis than did FN fragments (120-kDa cell-binding, 60-kDa
      heparin-binding, and 45-kDa collagen-binding). PDL cells harvested from diseased
      and healthy conditions were no different on the basis of these assays. These data
      demonstrate that PDL cells are a mixed population of fibroblastic cells, capable
      of forming a mineralized matrix. They also suggest that maximal proliferation and
      chemotaxis require specific FN domains that are present on the intact molecule
      but not its fragments.

PMID- 9776028
TI  - Relationship between conversion of localized juvenile periodontitis-susceptible
      children from health to disease and Actinobacillus actinomycetemcomitans
      leukotoxin promoter structure.
AB  - The periodontal pathogen Actinobacillus actinomycetemcomitans produces a
      leukotoxin that is considered a primary virulence factor in localized juvenile
      periodontitis (LJP). Select strains of the bacterium contain a 530-bp deletion in
      the promoter region of the leukotoxin gene operon which results in enhanced
      transcription of the leukotoxin. DNA hybridization and polymerase chain reaction
      (PCR) were used to examine genetic variants of A. actinomycetemcomitans in 24 LJP
      susceptible children from 21 families having a history of the disease and 34
      control children from non-LJP families. A significant association was found
      between the detection of variants that had a deletion in the leukotoxin promoter
      region, indicative of a high level expression leukotoxin genotype, and conversion
      from a healthy periodontal status to disease. Subjects harboring A.
      actinomycetemcomitans of this genotype were more likely to convert to LJP than
      those subjects who had variants containing the full length leukotoxin promoter
      region (odds ratio = 22.5; 95% C.I., 2.84 < 206.66) [corrected]. These findings
      support the concept that highly virulent strains or clonal types of periodontal
      pathogens play a major role in the initiation of periodontal disease in
      susceptible hosts.

PMID- 9776030
TI  - Guided tissue regeneration in Class II furcation involved maxillary molars: a
      controlled study of 8 split-mouth cases.
AB  - The purpose of this study was to clinically evaluate the effectiveness of
      polytetrafluoroethylene membranes in the healing of interproximal Class II
      furcation defects in maxillary molars using a surgical treatment technique based
      on the principles of guided tissue regeneration. Eight subjects with similar
      bilateral Class II furcation lesions on the mesial aspect of maxillary first
      molars participated in this study. Patients received initial therapy consisting
      of oral hygiene instructions, scaling and root planing, and occlusal adjustment
      if necessary. Clinical parameters evaluated included plaque index, sulcular
      bleeding index, probing depth, attachment level, gingival recession, and open
      horizontal and vertical furcation fill. An acrylic occlusal stent was used to
      assure reproducibility of measurements. Experimental sites received a
      polytetrafluoroethylene membrane following surgical exposure of the furcation.
      Control sites were treated in the exact same manner but without a membrane.
      Membranes were removed at 6 weeks after the first surgery. Reentry surgeries were
      performed at 9 months. Postsurgical results showed a significant improvement in
      probing depth, attachment level, and open horizontal furcation fill for both
      groups when compared to baseline values, with experimental sites performing
      significantly better than controls. Control sites showed a slight loss in open
      vertical furcation fill while experimental sites remained unchanged. This study
      suggests that guided tissue regeneration using polytetrafluoroethylene membranes
      is of some but limited value in the treatment of maxillary molar interpoximal
      Class II furcation lesions.

PMID- 9776031
TI  - Clinical evaluation of bioactive glass in the treatment of periodontal osseous
      defects in humans.
AB  - The purpose of this study was to compare the use of bioactive glass to
      demineralized freeze-dried bone allograft (DFDBA) in the treatment of human
      periodontal osseous defects. Fifteen systemically healthy patients (6 males and 9
      females, aged 30 to 63) with moderate to advanced adult periodontitis were
      selected for the study. All patients underwent initial therapy, which included
      scaling and root planing, oral hygiene instruction, and an occlusal adjustment
      when indicated, followed by re-evaluation 4 to 6 weeks later. Paired osseous
      defects in each subject were randomly selected to receive grafts of bioactive
      glass or DFDBA. Both soft and hard tissue measurements were taken the day of
      surgery (baseline) and at the 6-month re-entry surgery. The clinical examiner was
      calibrated and blinded to the surgical procedures, while the surgeon was masked
      to the clinical measurements. Statistical analysis was performed by using the
      paired Student's t test. The results indicated that probing depths were reduced
      by 3.07 +/- 0.80 mm with the bioactive glass and 2.60 +/- 1.40 mm with DFDBA.
      Sites grafted with bioactive glass resulted in 2.27 +/- 0.88 mm attachment level
      gain, while sites grafted with DFDBA had a 1.93 +/- 1.33 mm gain in attachment.
      Bioactive glass sites displayed 0.53 +/- 0.64 mm of crestal resorption and 2.73
      mm bone fill. DFDBA-grafted sites experienced 0.80 +/- 0.56 mm of crestal
      resorption and 2.80 mm defect fill. The use of bioactive glass resulted in 61.8%
      bone fill and 73.33% defect resolution. DFDBA-grafted defects showed similar
      results, with 62.5% bone fill and 80.87% defect resolution. Both treatments
      provided soft and hard tissue improvements when compared to baseline (P < or =
      0.0001). No statistical difference was found when comparing bioactive glass to
      DFDBA; however, studies with larger sample sizes may reveal true differences
      between the materials. This study suggests that bioactive glass is capable of
      producing results in the short term (6 months) similar to that of DFDBA when used
      in moderate to deep intrabony periodontal defects.

PMID- 9776032
TI  - Gingival crevicular pH in experimental gingivitis and occlusal trauma in man.
AB  - The purpose of this study was to investigate the fluctuation of gingival
      crevicular pH during experimentally evoked gingivitis and occlusal trauma, and to
      examine the relationship between the pH and periodontal health status using a
      newly developed pH sensor. Maxillary first premolars with clinically healthy
      gingiva were selected as test teeth in 10 volunteers. In the first study phase,
      experimental gingivitis was evoked, and gingival index, plaque index, and
      crevicular pH were recorded during the study period. In the second study phase,
      experimental occlusal trauma was created with metal onlays having occlusal
      interferences in lateral movements, and tooth mobility and pH were recorded
      during the study period. In the gingivitis phase, GI, PlI, and pH values
      fluctuated significantly during the study period (P < 0.01) and positive
      correlations were observed between both GI and pH values (P < 0.05), and PlI and
      pH values (P < 0.01). In the occlusal trauma phase, significant fluctuation was
      found among tooth mobilities (P < 0.05) during the study phase, but not in pH
      values. Statistically significant correlations were not observed between tooth
      mobilities and pH values. These data suggest that the crevicular pH level may not
      be influenced by experimental occlusal trauma, but shifts toward alkaline with
      experimental gingivitis.

PMID- 9776033
TI  - Preservation of alveolar bone in extraction sockets using bioabsorbable
      membranes.
AB  - The purpose of this study was to evaluate the clinical effectiveness of a
      bioabsorbable membrane made of glycolide and lactide polymers in preserving
      alveolar ridges following tooth extraction using a surgical technique based on
      the principles of guided bone regeneration. Sixteen patients requiring
      extractions of 2 anterior teeth or bicuspids participated in the study (split
      mouth design). Following elevation of buccal and lingual full-thickness flaps and
      extraction of teeth, experimental sites were covered with bioabsorbable
      membranes; control sites did not receive any membrane. Titanium pins served as
      fixed reference points for measurements. Flaps were advanced in order to achieve
      primary closure of the surgical wound. No membrane became exposed in the course
      of healing. Reentry surgeries were performed at 6 months. Results showed that
      experimental sites presented with significantly less loss of alveolar bone
      height, more internal socket bone fill, and less horizontal resorption of the
      alveolar bone ridge. This study suggests that treatment of extraction sockets
      with membranes made of glycolide and lactide polymers is valuable in preserving
      alveolar bone in extraction sockets and preventing alveolar ridge defects.

PMID- 9776034
TI  - Evaluation of periosteal membranes and coronally positioned flaps in the
      treatment of Class II furcation defects: a comparative clinical study in humans.
AB  - The purpose of this study was to compare the clinical effectiveness of connective
      tissue grafts including periosteum used as a mechanical barrier for guided
      periodontal tissue regeneration and coronally positioned flaps in the treatment
      of Class II furcation defects. A total of 28 furcation defects were treated; 14
      received a periosteal barrier and 14 received a coronally positioned flap.
      Reentry surgeries were performed at 6 months. No statistically significant
      differences were found preoperatively between the two treatment groups with
      respect to clinical parameters and osseous measurements. Postsurgically, both
      treatment modalities resulted in a significant decrease in probing depth and a
      significant gain in clinical attachment, but the differences observed were not
      statistically significant. The periosteal barrier group presented with a
      significantly better gain in vertical components of the alveolar bone (1.93 +/-
      0.15 mm and 0.20 +/- 0.26 mm for periosteal barrier and coronally positioned flap
      groups, respectively; P < or = 0.001) and horizontal components of the alveolar
      bone (1.60 +/- 0.21 mm and 0.13 +/- 0.90 mm for periosteal barrier and coronally
      positioned flap groups, respectively; P < or = 0.001). The results of this trial
      indicate that similar clinical resolution of Class II furcation defects can be
      obtained with periosteal barriers and coronally positioned flaps. Periosteal
      barriers, however, are a better treatment alternative in achieving bone fill of
      the furcation area.

PMID- 9776035
TI  - Alveolar bone levels in AIDS and HIV seropositive patients and in control
      subjects.
AB  - Alveolar bone levels were studied from intraoral radiographs of 24 non
      hospitalized patients with AIDS, 17 HIV seropositive subjects, and 39 matched
      control subjects. The AIDS/HIV subjects were seeking dental care in a faculty
      practice. The matched control subjects came from those non-HIV-infected patients
      seeking dental care at the University of Washington. Magnified intraoral
      radiographs were used to assess the distance between the cemento-enamel junction
      (CEJ) and the alveolar bone level (BL). The extent of vertical defects and
      furcation invasions was also assessed. The mean age of the AIDS, HIV, and control
      subjects was 38.9 +/- 6.6 years, 37.1 +/- 7.6, and 39.9 +/- 5.6, respectively,
      and was not statistically different. Among the AIDS patients, 75% were smokers,
      while 88.2% of the HIV subjects were cigarette smokers. Therefore, the matched
      control subjects were also smokers to the same extent. The mean difference in
      distance CEJ-BL was 0.1 mm (mesial) and 0.3 mm (distal) and greater in the
      HIV/AIDS group than in the control group, but not statistically different. No
      vertical defects > or = 3.0 mm were found in 69.2% of the control subjects and in
      58.5% of the combined HIV/AIDS group. None of the HIV/AIDS subjects had more than
      5 defects > 3.0 mm, while 7.6% of the control subjects had such defects.
      Significant associations were found between smoking and extent of alveolar bone
      loss (distance) (P < 0.001) as well as the number and extent of vertical defects
      (P < 0.01), but were not associated with HIV status. The extent of furcation
      invasions, as read radiographically, did not differ between groups. In
      conclusion, smoking but not HIV status was the primary factor for alveolar bone
      loss.

PMID- 9776036
TI  - The application of deproteinized bovine bone mineral for ridge preservation prior
      to implantation. Clinical and histological observations in a case report.
AB  - Alveolar ridge preservation following tooth extraction is important when implant
      supported oral rehabilitation is considered. The ability to maintain the ridge
      allows implant placement in an ideal position, fulfilling both functional and
      esthetic demands. A deproteinized bovine bone mineral (DBBM) was used as a socket
      site filler material to maintain ridge configuration, without applying an
      occlusive membrane. The material was grafted and packed onto the socket sites
      immediately after extractions, and subsequently primary soft tissue closure was
      attempted. The ridge healed for 9 months before the second surgical procedure, in
      which the implant was placed. New bone formation was observed in all histological
      specimens. DBBM particles adhered to a highly osteocyte-rich woven and lamellar
      type bone. Clinically and histologically, this report demonstrated DBBM particles
      to be an effective biocompatible filler agent in extraction sockets for ridge
      preservation prior to titanium fixture implantation. Randomized controlled
      clinical trials are needed to fully evaluate the usefulness of this material in
      ridge preservation after tooth extraction.

PMID- 9776037
TI  - Etiology of localized juvenile periodontitis.

PMID- 9776038
TI  - Acceptance Program Guidelines. Products and methods for the diagnosis and/or
      management of periodontitis. Council on Scientific Affairs. American Dental
      Association.
AB  - SCOPE: These Guidelines apply to the design of clinical trials to evaluate
      products and methods which are intended to be used for the detection and
      diagnosis of periodontitis. The general purpose for such products and methods
      would be to assist in the identification of sites or subjects with existing
      periodontitis or, at increased risk of periodontitis, or for the development or
      progression of periodontitis. Clinical use of such diagnostics might occur: 1)
      during initial evaluation (screening, pre-treatment risk assessment, diagnosis,
      treatment-planning); 2) during treatment or management (monitoring therapeutic
      endpoints, identifying therapeutic targets); and 3) post-treatment (establishment
      of recall intervals, early detection of recurrent disease). The specifics of
      clinical trial design for each of these related, but separate, clinical functions
      may differ depending on a variety of circumstances.

PMID- 9776040
TI  - Acceptance Program Guidelines. Products designed to regenerate periodontal
      tissues. Council on Scientific Affairs. American Dental Association.
AB  - SCOPE: These Guidelines apply to products used to promote the regeneration of
      periodontal tissues lost due to periodontal diseases or other causes. Periodontal
      regeneration is defined histologically as regeneration of the tooth's supporting
      tissues, including alveolar bone, periodontal ligament, and cementum over a
      previously diseased root surface. Regenerative procedures must enhance the
      formation of a new attachment apparatus demonstrated by randomized controlled
      histological studies in animals, verified by human histologic evidence, and
      supported by beneficial results in human randomized controlled clinical trials.

PMID- 9776039
TI  - Acceptance Program Guidelines. Chemotherapeutic agents to slow or arrest
      periodontitis. Council on Scientific Affairs. American Dental Association.
AB  - SCOPE: These Guidelines apply to products used to slow or arrest periodontitis.
      The periodontal diseases represent a wide array of infections characterized by
      variable microbial clusters and host susceptibility factors that may require
      different therapeutic approaches. There are two basic ways to control
      periodontitis: 1) target the putative microbial components with anti-infective
      strategies; or 2) strengthen or suppress the host response with host modulation
      agents. Products that are designed for the prevention and/or control of
      gingivitis are addressed elsewhere and are not considered in these guidelines.

PMID- 9776041
TI  - Photolysis and membrane lipid peroxidation of human erythrocytes by m
      chloroperbenzoic acid.
AB  - The aim of the present work was to investigate the biological hazard of
      photooxidation products of m-chloroperbenzoic acid (mCPBA), as a novel photo
      sensitizer, on lysis and membrane lipid peroxidation of human red blood cells
      (RBC). The photohemolysis activity of mCPBA oxidative products was concentration-
      and exposure time-dependent. Ten minutes photoexposure time and 100 micromol/L of
      mCPBA concentration were optimum to study the effect of generated superoxide (O2.
      ) and hydroxyl (.OH) radicals on RBC. The hemolytic effect of mCPBA was highly
      significantly inhibited by formate (as an .OH radical scavenger) compared with
      the partial inhibition effect of SOD-like Cu(II) complex (as O2.- radical
      Scavenger). The MDA value (an end product of membrane lipid peroxidation of RBC)
      induced by mCPBA was highly significantly decreased by formate. The generation of
      O2.- radicals by mCPBA was also confirmed by the partial hemolytic effect of
      phenazine methosulfate (PMS., O2.- radical generation). The data suggest the
      molecular mechanism of the oxygen radical species (O2.- and .OH through the
      photosensitization reaction of mCPBA and explain that hydroxyl radicals (.OH)
      play an active role in the photohemolysis process and peroxidation of membrane
      lipids of human erythrocytes.

PMID- 9776042
TI  - Changes in intestinal alkaline phosphatase isoforms in healthy subjects bearing
      the blood group secretor and non-secretor.
AB  - We found the high molecular mass intestinal alkaline phosphatase (HIAP) and
      normal molecular mass intestinal alkaline phosphatase (NIAP) in serum at fasting
      and after fatty meal by use of 6.0% polyacrylamide gel electrophoresis (PAGE) in
      the presence of 1% Triton X-100. HIAP only appeared in serum of Lewis blood group
      secretors ?Le(a-b+)?, and HIAP levels were dependent on ABO blood groups. Among
      the secretors, the highest activities of HIAP in fasting serum were observed in
      subjects with blood groups O and B (8.6+/-1.4 U/1; mean+/-SD) and the lowest
      activities were associated with blood group A (0.7+/-0.2 U/1; mean+/-SD), and the
      HIAP activities did not change after fatty meal. In contrast, NIAP was present in
      the serum of both secretors and non-secretors regardless of ABO blood group.
      Trace amounts of NIAP remained in fasting serum; however serum NIAP activities
      rose sharply after fatty meal. The remaining ratios of NIAP activity at fasting
      and 9 h after fatty meal of secretors were approximately the same as those of non
      secretors. The electrophoretic mobility on PAGE or the apparent molecular mass
      estimated by gel filtration of serum NIAP in secretors was slightly different
      from that in non-secretors. In addition, HIAP can be normalized to NIAP on PAGE
      in the absence of Triton X-100, and the electrophoretic mobility of normalized
      NIAP was identical to that of original NIAP in secretors. Accordingly, it can be
      concluded that the structure of serum NIAP in the secretor was different from
      that in the non-secretor, because HIAP is only formed by serum NIAP in the
      secretor. These results suggest that differences in serum NIAP in the secretor
      and the non-secretor may be closely related to the appearance of IAP in the
      circulation.

PMID- 9776043
TI  - Effect of nicotine and cotinine on the susceptibility to in vitro oxidation of
      LDL in healthy non smokers and smokers.
AB  - Cigarette smoke of which the major component is nicotine plays an important role
      in the development of cardiovascular diseases. To study the effect of in vitro
      incubation of LDL with nicotine and its metabolite, cotinine on a copper-induced
      peroxidation, we monitored the formation of conjugated dienes, hydroperoxides and
      thiobarbituric acid-reactive substances production. The LDL studied were taken
      from six non-smokers (aged 41.5 years) and six smokers who consumed at least ten
      cigarettes per day (40.7 years). LDL oxidation with CuSO4 showed that cigarette
      smoking promotes LDL susceptibility to peroxidative modification. During the
      peroxidation of LDL with nicotine (O to 5 mmol/1) and CuSO4 (5 micromol/l), the
      formation of hydroperoxides decreased when nicotine concentrations increased and
      the production of TBARS increased in a concomitant manner. The results showed
      that the presence of nicotine destabilized the production of hydroperoxides in
      LDL and increased the formation of secondary oxidation products. On the other
      hand, cotinine had no effect on LDL oxidative susceptibility in smokers and non
      smokers.

PMID- 9776044
TI  - Assay of beta-N-acetylhexosaminidase isoenzymes in urine by means of
      determination of their activation energy without removing endogenous low
      molecular-mass components.
AB  - The determination of the activation energy of beta-N-acetylhexosaminidase (Hex,
      EC 3.2.1.52), using 3,3'-dichlorophenylsulfonphthaleinyl-N-acetyl-beta-D
      glucosaminide as substrate, allows its isoenzyme composition to be evaluated in
      different biological specimens. However, in the analysis of urine samples, it is
      necessary first to remove the endogenous low-molecular-mass components, as these
      provoke an over-estimation of the activation energy of the Hex and, consequently,
      of the relative proportion of Hex B isoenzyme. The study of this interference has
      allowed urea to be characterised as the only urinary metabolite that is
      responsible, and to establish a mathematical expression for the correction, in
      relation to the endogenous urea concentration, of the activation energy of the
      Hex obtained experimentally in samples of native urine. The results thus obtained
      for the isoenzyme composition of urinary Hex are similar to those found using an
      electrophoretic separation procedure.

PMID- 9776046
TI  - Evaluation of the Abbott system in maternal serum screening for Down syndrome:
      the AxSym analyzer, AFP and hCG reagents and Maciel Prenatal Interpretive
      Software.
AB  - Multi-marker maternal serum screening for Down syndrome in the second trimester
      is now part of routine care in many centers. Most protocols use a combination of
      hCG (or its free beta-subunit) and alpha-fetoprotein (AFP) or unconjugated
      estriol (UE3), or both. Risk calculation is based on these maternal serum marker
      values combined with maternal age and trisomy 21 maternal age-related risk.
      Computer programs are therefore necessary. Both technical and statistical
      efficiency are included in the final risk evaluation. We studied the Abbott
      system, comprising AxSym analyzer, AFP and hCG kits and Prenatal Interpretive
      Software (Maciel). Median values were established between 14 and 18 weeks of
      amenorrhea in a population of 1822 patients and in twin pregnancies in 157 cases.
      Forty maternal sera from trisomy 21 affected pregnancies were analyzed. Software
      was evaluated in a population of 429 patients and in 124 cases of trisomy 21. We
      conclude that this system constitutes an accurate and efficient method of
      maternal serum screening for Down syndrome.

PMID- 9776045
TI  - Determination of silicon in urine by inductive coupled plasma-optical emission
      spectroscopy.
AB  - We describe an inductive coupled plasma-optical emission spectroscopic method to
      determine silicon in spot urine specimens. A 6-fold standard addition series of
      the urine specimen ranging from 0 to 356 micromol/l silicon was applied, and the
      method meets the requirement of matrix compensation in a frequently changing
      environment. The inter-assay variation was +/-3.0%, intra-assay variations for
      three specimens were +/-1.7%, +/-1.1% and +/-0.84%. To compensate for
      physiological variations of urine density, the silicon concentrations in urine
      were related to urinary creatinine which was measured in parallel by reversed
      phase HPLC. Urinary silicon concentrations were examined in 43 healthy controls
      from the local population. The 5th-95th percentile was 12.6-237 micromol/mmol
      creatinine. A follow-up of three people over a period of 14 days showed that
      intra-individual variations of urinary silicon concentrations were smaller than
      variations between individuals, especially when silicon is related to creatinine.

PMID- 9776047
TI  - Atypical neutrophil alkaline phosphatase associated with impaired neutrophil
      functions.
AB  - We report the case of a healthy young man presenting with atypical neutrophil
      alkaline phosphatase (NAP) and reduced neutrophil chemotactic activity, but with
      no susceptibility to infection. NAP activity was low, kinetic parameters were
      modified and immunoreactive properties and subcellular distribution were
      abnormal. Neutrophil morphology was normal. A similar pattern was observed in the
      patient's healthy brother. The profile of the observed anomalies offers some
      similarity to that previously described in patients with chronic myelogenous
      leukaemia. However, in the present case, the NAP deficiency with impaired
      neutrophil function was present in two brothers with no haematological symptoms
      and is probably related to a non-acquired neutrophil abnormality. This
      observation of a primary NAP variant reinforces the hypothesis of a direct link
      between NAP activity and functional properties of neutrophils.

PMID- 9776048
TI  - A study on the carotid artery intima-media thickness and its association with
      lipid peroxidation.
AB  - High resolution B-mode ultrasonography of the carotid arteries has been used to
      investigate the signs of early atherosclerotic vessel wall disease by measuring
      the intima-media thickness (IMT). We examined the association between IMT and
      lipid peroxidation and found IMT to be increased in a group of patients with
      respect to controls (1.430+/-0.341 mm versus 0.703+/-0.201 mm, P < 0.001). Plasma
      and erythrocyte malondialdehyde (MDA) levels were also significantly higher
      (P<0.001) and the erythrocyte reduced glutathione (GSH) levels were significantly
      lower (P <0.001) in the patients with respect to the controls. In the groups of
      patients there was no significant correlation between the mean IMT and the plasma
      and erythrocyte MDA levels or the erythrocyte GSH levels. In conclusion
      determination of lipid peroxides would be especially important and advisable in
      patients with increased carotid IMT. Type II diabetes and hypertension were also
      associated with increased IMT.

PMID- 9776049
TI  - A case of multiple myeloma IgG(lambda)type with low molecular weight kappa light
      chain.

PMID- 9776050
TI  - Observations on ploidy of cells and on reproductive performance in
      parthenogenetic turkeys.
AB  - Using flow cytometry, the ploidy levels of parthenogenetic turkeys were
      quantified from blastodisc stage to adulthood. Eggs were collected from
      noninseminated hens of the Beltsville Small White flock, known for their high
      degree of parthenogenesis, and the blastodermal cells from developing embryos
      were compared with those of embryos produced by hens inseminated with semen from
      males of the same flock. Erythrocytes of parthenogens from Day 10 of incubation
      to 27 mo of age were also used for ploidy determination. Sperm and erythrocyte
      preparations from normal males of the above flock served as haploid and diploid
      standards, respectively. In parthenogenetically developing blastoderms, 40.3 +/-
      14.5% of the cells were haploid and 48.9 +/- 11.9% diploid; blastoderms from
      fertilized eggs had no haploid cells. The haploid cell content of parthenogens
      declined from the blastodermal stage to adult life, with 1.9 +/- 2.3% at 10 to 20
      d of embryonic development, 1.5 +/- 1.4% at 21 to 29 d of development, 1.4 +/-
      2.6% at 4 wk posthatch, and 1.3 +/- 1.9% in adulthood, although changes between
      the 1st mo after hatch and adult stage were not significant. It is possible,
      therefore, that parthenogenetic embryos with a low proportion of haploid cells
      could be the ones that survive to Day 10 of development and beyond, whereas those
      with a higher proportion of haploid cells fail to develop. The semen volume of
      male parthenogens was significantly lower than that of normal males, although the
      concentration of spermatozoa and their fertilizing capacity did not vary
      significantly between groups, suggesting that the germ cells of these
      parthenogens are capable of normal meiosis and sperm maturation leading to a
      normal fertility.

PMID- 9776051
TI  - Differentiating between parthenogenetic and "positive development" embryos in
      turkeys by molecular sexing.
AB  - In mated or inseminated turkeys, 5 to 15% of eggs set for incubation show only
      rudimentary development. Most of these embryos die during the first 24 to 48 h of
      incubation and contain only unorganized sheets of tissue. This abnormal
      development is termed "positive development" (PD). Turkey eggs also show
      incidence of parthenogenesis and the resulting progeny is believed to be always
      male. As both types of embryos are morphologically similar at the early stage of
      incubation, it has been speculated that PD embryos may in fact be parthenogens.
      By identifying the sex at the blastodermal stage with the help of DNA markers, we
      have differentiated between the PD embryos and parthenogens. Parthenogenetic
      embryos were obtained from eggs laid by uninseminated or virgin Beltsville Small
      White (BSW) hens, and the PD embryos were obtained from eggs of inseminated
      Nicholas and British United Turkeys of America (BUTA) hens. DNA was extracted
      from blastoderms of parthenogenetic and PD embryos. Turkey W-chromosome specific
      DNA probe and primers were used to detect females in all samples by Southern blot
      and polymerase chain reaction (PCR), respectively. No female was detected among
      the 35 parthenogens examined, whereas there were 3 females among the 11 PD
      embryos. The presence of both males and females among PD embryos suggests that
      they are products of fertilization, and that at least these 3 female embryos, if
      not all the 11 PD embryos, are not of parthenogenetic origin. It is concluded,
      therefore, that PD embryos result from errors in fertilization or from early
      embryonic mortality following successful fertilization, and that they are
      unlikely to be of parthenogenetic origin.

PMID- 9776052
TI  - Forty generations of bidirectional selection for mating frequency in male
      Japanese quail.
AB  - A bidirectional replicated selection experiment for high (H1 and H2) or low (L1
      and L2) cumulative number of complete matings (CNCM) in male Japanese quail was
      conducted for 40 generations. In the S32 generation, a subline was taken from
      each selected line and selection was relaxed. In the randombred control line (C),
      CNCM and unselected traits changed significantly over generations. Means of the
      selected lines were adjusted each generation for deviations from the control
      means. After 40 generations of selection, there was a 21-fold difference in CNCM
      (59.4 vs 2.8) between Lines H1 and L1. Whereas means increased and variation
      decreased in the high lines, means decreased and variation increased in the low
      lines. Regressions of mean CNCM on generation of Lines H1, H2, L1, and L2 were
      1.15 +/- 0.08, 0.61 +/- 0.08, -0.26 +/- 0.04, and -0.34 +/- 0.03, respectively.
      Although responses to selection were observed throughout the 40 generations in
      Line H1, the low lines appeared to have reached a limit to selection after the
      S30 generation. Relaxed lines provided supporting evidence for this conclusion.
      Mean CNCM decreased in the relaxed high lines to that of the control, whereas the
      low relaxed lines remained at the same level as their corresponding selected
      lines. Line H2 went into extinction in the 37th generation as a result of reduced
      fitness. Realized heritabilities of CNCM were 0.09, 0.07, 0.06, and -0.15 in
      Lines H1, H2, L1, and L2, respectively. As correlated responses to the selection,
      male quail in the high lines were heavier, exhibited greater relative
      aggressiveness, and had larger cloacal glands than those of the control and low
      lines.

PMID- 9776053
TI  - Hematocrit values in weight-selected and relaxed lines of White Rock chickens.
AB  - Hematocrits (PCV) were measured at 29 and 106 d of age (PCV1 and PCV2,
      respectively) in male and female White Plymouth Rocks. Four lines were used, two
      of which had undergone 40 generations of divergent selection for 8-wk BW (HWS,
      LWS), and two respective sublines (HWR, LWR), in which selection had been relaxed
      for five generations. At both ages, males and females did not differ for PCV in
      lines HWR, LWR, and LWS. For line HWS there was an age by sex interaction that
      resulted from an age effect for males but not for females, and from a sex effect
      at each age. At both ages, PCV was higher for the HW than the LW lines.
      Initially, there was no difference between the selected and their respective
      relaxed lines, but by 106 d, HWR chickens had a higher PCV than HWS chickens. In
      lines HWR and LWR, PCV increased with age. There was a negative correlation in
      HWS males for PCV1 with 28 and 56 d BW. The HWR males also had a negative
      correlation for PCV1 with BW at 28 d, but not between PCV2 and BW. The
      correlation for PCV1 with PCV2 was high and positive for HWR males and females.

PMID- 9776054
TI  - The effect of dietary crude protein on growth, ammonia concentration, and litter
      composition in broilers.
AB  - An experiment was conducted to determine the effect of diets with reduced CP and
      supplemental amino acids on broiler performance, N excretion, litter
      characteristics, and equilibrium NH3 gas concentration. Results suggest that
      reducing CP (and lysine) below 241 g/kg (13.7 g/kg lysine) in the diets fed
      during the first 3 wk may slightly increase feed:gain and therefore may not be
      advisable. During the period 22 to 43 d of age there were no significant
      differences in weight gain and BW at 6 wk of age when reducing CP from 215 g/kg
      (11.5 g/kg lysine) to 196 g/kg (11.3 g/kg lysine), but feed intake and feed:gain
      ratio increased. However, reducing CP did cause equilibrium NH3 gas concentration
      and litter N to decline by 31 and 16.5%, respectively. Both of these advantages
      will improve air quality within the housing facility and possibly reduce heating
      costs during winter associated with higher ventilation rates required to reduce
      elevated NH3 gas concentrations.

PMID- 9776055
TI  - Sodium chloride concentration in drinking water and eggshell quality.
AB  - Two experiments with White Leghorn hens (36 and 49 wk old, respectively) were
      conducted to examine the effects of varying NaCl concentrations provided through
      drinking water upon eggshell quality. Experiments were of 6 and 5 wk duration,
      respectively. Seven replicate pens of five individually caged hens received each
      water treatment. Treatments were the same in both studies and consisted of low-Na
      (9 ppm) tap water supplemented with 0, 200, 400, 600, or 800 ppm NaCl. Solutions
      were prepared weekly. All eggs produced were examined visually for shell defects,
      and egg weight and specific gravity were determined. In the second experiment,
      eggs from 2 consecutive d were also broken out each week for Haugh Unit
      determinations. In both studies, hen-day egg production, daily feed and water
      intake, egg weight, and body weight change over the experimental period were not
      influenced by any level of waterborne NaCl. Haugh Units were also not affected in
      Experiment 2. In contrast to other literature reports, visually determined shell
      defects and egg specific gravity were not adversely affected by NaCl
      supplementation of layer drinking water.

PMID- 9776056
TI  - Effect of housing birds in cages or an aviary system on bone characteristics.
AB  - Sixty-nine-week-old brown egg layers were either maintained in cages or moved to
      a litter-floored aviary system. After 10 or 20 d, birds were selected at random
      from within each environment, and their tibiae removed. After drying, bones were
      measured and then subject to various physical measurements of strength and
      elasticity. Bone ash and bone calcium content were also measured. Birds
      maintained in an aviary initially had stronger bones as measured by force (P <
      0.05). After 20 d in an aviary, birds had stronger bones, as assessed by force,
      than their contemporaries maintained in cages. This same relationship was seen in
      measures of bone stress (P < 0.05). After 20 d in the aviary system, previously
      caged birds had bone ash values that were intermediate between birds held only in
      cages or the aviary (P > 0.05). Bone calcium content was not influenced by the
      bird's environment. It appears that the skeleton of caged birds can be affected
      by providing them with an environment that allows opportunity for increased
      static and dynamic loading of the bones.

PMID- 9776057
TI  - Salmonella prevalence in crops of Ontario and Quebec broiler chickens at
      slaughter.
AB  - Swabs of crop contents of 635 broiler chickens were obtained from 9 Ontario and
      12 Quebec processing plants and cultured for Salmonella to determine prevalence
      in broiler crops. Serotypes of positive cultures were determined to evaluate the
      serotype profile. The overall prevalence of contamination was low (4.3%).
      Prevalence was higher in broilers sampled in Quebec (5.8%) than in those sampled
      in Ontario (2.2%). In Quebec, there were differences in prevalence among the
      groups of broilers sampled at the various plants. These differences were believed
      to be attributable to differences in Salmonella prevalence among groups of flocks
      delivered to the plants due to the limited exposure of the chickens to the plant.
      The serotype profile of Salmonella isolated from the crops of broilers in this
      study was similar in several respects to profiles obtained from other surveys of
      Canadian broiler flocks using either environmental samples or cloacal swabs.
      Similarities included: predominance of Salmonella hadar and Salmonella
      heidelberg; several other common serotypes at a low prevalence; little Salmonella
      enteritidis isolated in other studies, and no S. enteritidis isolated in this
      study. Results of this field survey of Salmonella in crops of broilers are
      similar to those of Canadian studies of other internal and environmental sites of
      broilers. The similarity indicates that monitoring of Salmonella environments of
      flocks of live broiler chickens should define profiles of Salmonella
      contamination of the carcasses and would also aid in determination of Salmonella
      contamination status of broiler flocks. Such information would assist efforts to
      reduce Salmonella contamination in broiler chickens.

PMID- 9776058
TI  - Effects of a hydrated sodium calcium aluminosilicate (T-Bind) on mycotoxicosis in
      young broiler chickens.
AB  - Experiments were conducted to determine the ability of a hydrated sodium calcium
      aluminosilicate (T-Bind) sorbent to reduce the toxicity of aflatoxins (AF) or T-2
      toxin in male broiler chickens from day of hatch to 21 d of age. In Experiment 1,
      the sorbent was added at 0.250 or 0.375% to diets containing AF at 5 or T-2 toxin
      at 8 mg/kg of diet. When compared with controls, AF reduced BW gain by 27% and T
      2 toxin reduced BW gain by 17%. The addition of the sorbent at 0.250 or 0.375%,
      in the absence of added mycotoxins, did not alter the performance of the chicks.
      The sorbent reduced the toxic effects of 5 mg AF/kg of diet on BW gain by 43% but
      did not significantly diminish the toxic effects of 8 mg T-2 toxin/kg of diet.
      The decreased efficiency of feed utilization and the increased relative organ
      weights caused by AF were significantly diminished to differing degrees by the
      sorbent. Oral lesions caused by T-2 toxin were not affected by the sorbent. In
      Experiment 2, the sorbent was added at 0.80% to a diet containing 8 mg T-2
      toxin/kg of diet. The sorbent did not diminish the toxic effects of T-2 toxin
      when added at 0.80% of the diet. These data demonstrate that this specific
      sorbent can provide protection against the toxicity of AF, but not T-2 toxin, in
      young broiler chicks.

PMID- 9776059
TI  - Intracellular accumulation, subcellular distribution, and efflux of tilmicosin in
      chicken phagocytes.
AB  - Tilmicosin is a semi-synthetic macrolide antibiotic, currently approved for
      veterinary use in cattle and swine respiratory disease, and is in development for
      use in poultry mycoplasma air sacculitis. In order to provide an understanding of
      clinical efficacy, the in vitro interaction of tilmicosin with three types of
      chicken phagocytes (MQ-NCSU macrophages, monocyte-macrophages, and heterophils)
      was evaluated. After incubation with radiolabeled tilmicosin, uptake was
      determined and expressed as the ratio of the cellular (Cc) to the extracellular
      (Ce) drug concentration (Cc:Ce). Tilmicosin was avidly accumulated by heterophils
      (Cc: Ce 138 at 4 h incubation vs 32 and 66, respectively, in MQ-NCSU and monocyte
      macrophages) with 61 to 88% localized in the lysosomes. Uptake was dependent on
      cell viability, temperature, and pH, but was not influenced by metabolic
      inhibitors. However, phagocytosis of Pasteurella multocida and lipopolysaccharide
      exposure increased tilmicosin uptake by the chicken phagocytes. Upon removal of
      extracellular tilmicosin, 50% of the intracellular tilmicosin was effluxed within
      the first 30 min, but after 4 h of incubation in antibiotic-free medium, 30%
      remained cell-associated. Opsonized P. multocida significantly enhanced the
      release of tilmicosin from all three types of chicken phagocytes. Tilmicosin
      uptake was observed to increase lysosomal enzyme (acid phosphatase, lysozyme,
      avidin, and beta-glucuronidase) production. Finally, neutrophils were shown to
      transport and efflux bioactive tilmicosin in a test system measuring both
      neutrophil chemotaxis under agarose and a bioassay measuring inhibition of
      bacterial growth in the presence of antibiotic in agar. These in vitro
      observations of cellular pharmacology suggest a complex interaction between
      phagocytes and tilmicosin that contribute to clinical efficacy.

PMID- 9776061
TI  - A comparison of Escherichia coli levels at four sampling sites on turkey
      carcasses.
AB  - The objective of this study was to investigate the levels of Escherichia coli on
      different sites of turkey carcasses by sponge sampling using a 50 cm2 template.
      The breast, thigh, back, and cavity sites were sampled to determine which sites
      would be suitable for quantifying E. coli levels for the purpose of assessing
      control of the slaughtering and chilling processes. Results show that the breast
      and cavity sites have the lowest levels of E. coli (2.6 and 2.7 cfu/cm2,
      respectively), whereas thigh and back sites have the highest (6.7 and 7.6
      cfu/cm2, respectively). Data analyses indicate that E. coli levels at the breast
      and cavity site are lower (P < 0.05) than the other sites. A composite sample
      consisting of thigh and back sites for E. coli testing is recommended for
      assessing process control in turkey slaughtering facilities.

PMID- 9776060
TI  - Effects of dietary fat and eggshell cuticle removal on egg water loss and embryo
      growth in broiler hatching eggs.
AB  - The effects of dietary fat and eggshell cuticle removal on egg water loss, embryo
      growth, and hatchability were determined in eggs from broiler breeder hens at
      different ages. Hens were fed isocaloric diets containing one of three different
      types and levels of added fat. In addition, eggs were either left intact or
      washed to remove the eggshell cuticle prior to set. Cuticle removal increased egg
      water loss between 43 and 62 wk. Cuticle removal increased relative wet embryo
      weight at Week 52 and relative dry embryo weight at 52 and 62 wk. Furthermore, at
      62 wk, diet and day of incubation interacted to affect wet embryo weight, and
      diet variably affected dry embryo weight. No treatment differences were observed
      for cumulative hatchability, rate of hatch, and relative yolk sac weight at Day
      19 of incubation. It was concluded that cuticle removal and the addition of fat
      to breeder diets may influence embryonic growth without having any subsequent
      effects on hatchability.

PMID- 9776062
TI  - The inhibitory effect of carboxymethylcellulose with high viscosity on lipid
      absorption in broiler chickens coincides with reduced bile salt concentration and
      raised microbial numbers in the small intestine.
AB  - Two diets, with or without a nonfermentable carboxymethylcellulose (CMC) with
      high viscosity, were fed to broiler chickens beginning at 2 wk of age to study
      whether the anti-nutritive effect of gelling fibers on lipid digestibility may be
      associated with reduced intestinal bile salt concentration. Moreover, the
      microflora were examined to study whether possible changes in bile salt
      concentration coincide with alterations in microbial numbers.
      Carboxymethylcellulose depressed apparent lipid digestibility (P = 0.021). Feed
      intake and weight gain were not significantly affected. Water intake was
      increased in birds fed the CMC diet (P = 0.039). Bile acid concentration in small
      intestinal digesta was decreased (P = 0.047) in birds fed the CMC diet, which may
      have been caused by the increased water content of digesta (P < 0.001). The
      concentration of bile acids per gram dry matter or per milligram chromium was not
      reduced in small intestinal contents. Broiler chickens fed the CMC diet excreted
      more bile acids in the excreta (P < 0.001). Total aerobic and anaerobic microbial
      counts in the intestinal digesta were significantly increased in the duodenum
      plus jejunum (P = 0.038) but not in the ileum. Significant increases were found
      in the numbers of Clostridia (P = 0.017), Lactobacillus (P = 0.009), Bacteroides
      (P = 0.022), and yeasts and molds (P = 0.012). The present study supports the
      hypothesis that a nonfermentable gelling fiber (CMC) decreases apparent lipid
      digestibility by reducing the concentration of bile acids in the chyme in broiler
      chickens. Moreover, the ingestion of gelling fibers may increase the bacterial
      activity in the small intestine, which may further contribute to malabsorption of
      lipids.

PMID- 9776063
TI  - Studies on the effect of feeding cupric sulfate pentahydrate to laying hens on
      egg cholesterol content.
AB  - Two experiments were conducted to test the hypothesis that pharmacological levels
      of dietary Cu could reduce egg cholesterol content. White Leghorn hens 30 to 39
      wk of age were fed corn and soybean meal diets with 0, 125, or 250 mg
      supplemental Cu/kg diet from cupric sulfate pentahydrate (basal diet = 6.74 mg
      Cu/kg). Body weight, feed consumption, egg weights, egg specific gravity, and
      Haugh Units were not consistently affected during the 8-wk feeding trials. Egg
      production was significantly increased (P < 0.05) in the second 4-wk period by
      supplemental Cu in both experiments. Egg yolk cholesterol concentrations were
      decreased by feeding 125 mg Cu/kg diet (11.7 vs 8.6 mg/g, average of two
      experiments); feeding 250 mg Cu/kg resulted in further declines in egg
      cholesterol but the differences were not significant (7.9 mg/g). Changes in
      plasma cholesterol concentrations were similar to those of yolk cholesterol.
      Small but significant amounts of Cu accumulated in the yolks and shells of eggs
      from Cu-supplemented hens; however, most of the Cu fed was found in the excreta.

PMID- 9776064
TI  - Bioavailability of zinc in two zinc sulfate by-products of the galvanizing
      industry.
AB  - Two Zn depletion/repletion assays were conducted with chicks to determine the
      relative bioavailability (RBV) of Zn from two new by-products of the galvanizing
      industry. Using a soy concentrate-dextrose diet, slope-ratio methodology was
      employed to evaluate two different products: Fe-ZnSO4 x H2O with 20.2% Fe and
      13.0% Zn, and Zn-FeSO4 x H2O with 14.2% Fe and 20.2% Zn. Feed-grade ZnSO4 x H2O
      was used as a standard. Weight gain, tibia Zn concentration, and total tibia Zn
      responded linearly (P < 0.01) to Zn supplementation from all three sources. Slope
      ratio calculations based on weight gain established average Zn RBV values of 98%
      for Fe-ZnSO4 x H2O and 102% for Zn-FeSO4 x H2O, and these values were not
      different (P > 0.10) from the ZnSO4 standard (100%). Slope-ratio calculations
      based on total tibia Zn established average Zn RBV values of 126% for Fe-ZnSO4 x
      H2O and 127% for Zn-FeSO4 x H2O, and these values were greater (P < 0.01) than
      those of the ZnSO4 standard (100%). It is apparent that both mixed sulfate
      products of Fe and Zn are excellent sources of bioavailable Zn.

PMID- 9776065
TI  - Dietary threonine responses in growing turkey toms.
AB  - A study was conducted to evaluate Thr responses in Large White (British United
      Turkeys) male turkeys during three time periods: 0 to 3, 3 to 6, and 6 to 9 wk of
      age. The Thr-deficient diets, fed in 3-wk intervals, were composed primarily of
      corn, peanut meal, poultry meal, and soybean meal as intact protein sources and
      supplemented with amino acids. Graded levels of L-Thr were added to the Thr
      deficient diets. Another group of turkeys received a corn-soybean-poultry meal
      control diet in each time period. Diets were formulated to meet a minimum of 110%
      of suggested amino acid specifications (NRC, 1994) for all essential amino acids,
      except Thr. Feed intake, BW gain, and feed:gain responses were measured. Average
      environmental temperatures for Weeks 1, 2, and 3 were 29, 27, and 24 C,
      respectively. From 4 to 9 wk of age, average environmental temperatures varied
      between 24 and 35 C. Turkeys in each time period responded to Thr in a
      curvilinear manner with responses at the asymptote being equivalent to turkeys
      fed the corn-soybean meal control diets. Adequate dietary Thr levels for gain and
      feed:gain for the 0 to 3 wk period were 0.93% (3.21 g Thr/Mcal ME) and 0.97%
      (3.34 g Thr/Mcal ME) of diet, respectively. From 3 to 6 wk of age, the level of
      dietary Thr needed to support adequate BW gain and feed:gain was 0.88% of diet
      (2.81 g Thr/Mcal ME). The level of dietary Thr needed to support adequate BW gain
      and feed:gain from 6 to 9 wk of age was 0.77% of diet (2.30 g Thr/Mcal ME). These
      results indicate that the NRC (1994) estimations of Thr needs up to 9 wk of age
      are more than adequate.

PMID- 9776066
TI  - Hepatic export of glutathione and uptake of constituent amino acids, glutamate
      and cysteine, in broilers in vivo.
AB  - This study was conducted to document the glutathione (GSH) cycle (interorgan
      circulation of GSH) in broilers in vivo. Two experiments were conducted on 36
      anesthetized male broilers (n = 6 per treatment) implanted with cannulae in the
      carotid artery, hepatic portal, and hepatic veins. Plasma GSH, glutamate,
      cysteine, cystine, and cysteinylglycine levels in each vessel were monitored
      following a bolus injection [Experiment (Exp.) 1] or 30 min continuous infusion
      (Exp. 2) of GSH, or a gamma-glutamyltranspeptidase inhibitor (AT125) into the
      hepatic portal vein. Controls received saline alone. The GSH and AT125 treatments
      were used to determine the effect of increasing the prehepatic GSH load and of
      inhibiting systemic GSH degradation, respectively, on the GSH cycle. Hepatic
      export of GSH was clearly evident in all three treatment groups in both
      experiments (Exp.). The GSH and AT125 treatments raised amino acid levels in some
      or all of the vessels, whereas cysteinylglycine was elevated by AT125 and
      depressed by the GSH treatment compared to Controls. Hepatic uptake of glutamate,
      cysteine, and/or cystine was observed in Controls and GSH-treated birds, but not
      in birds given AT125 (Exp. 2). Neither hepatic export nor uptake of
      cysteinylglycine was observed in any treatment group. The results clearly
      demonstrate the ability of the avian liver to export GSH into the general
      circulation despite alterations that might arise from changes in extra-hepatic
      ability to utilize GSH or its constituent amino acids.

PMID- 9776067
TI  - Evaluation of minimally invasive indices for predicting ascites susceptibility in
      three successive hatches of broilers exposed to cool temperatures.
AB  - Broilers from three consecutive hatches were exposed to cool temperatures to
      amplify the incidence of pulmonary hypertension syndrome (PHS, ascites). The
      largest apparently healthy individuals on Day 42 were evaluated using minimally
      invasive diagnostic indices [percentage saturation of hemoglobin with oxygen,
      hematocrit (HCT), heart rate, electrocardiogram (ECG) Lead II, body weight), then
      they were subjected to the ongoing pressures of fast growth and cool temperatures
      to determine which of these indices are predictive of the subsequent onset of
      PHS. Approximately 20% of the males and females evaluated on Day 42 subsequently
      developed PHS by Day 51. When data for all hatches were pooled and broilers that
      subsequently developed ascites were compared with those that did not
      (nonascitic), body weights, heart rates, and percentage saturation of hemoglobin
      with oxygen were lower on Day 42 for ascitic than for nonascitic males, and HCT
      was higher in ascitic males and females than in nonascitic males and females,
      respectively. Comparisons of the ECG Lead II wave amplitudes for all hatches
      pooled indicated that RS-wave amplitude was larger in ascitic than in nonascitic
      males, and that S-wave amplitude was more negative in ascitic males and females
      than in nonascitic males and females. Necropsies conducted on Day 51 revealed
      higher right:total ventricular weight ratios in ascitic than in nonascitic
      broilers, whereas normalizing the left ventricle plus septum weight for
      differences in body weight generated similar values for ascitic and nonascitic
      males and females, respectively. These results support a primary role for
      pulmonary hypertension but not cardiomyopathy in the pathogenesis of ascites
      triggered by cool temperatures. Values obtained for minimally invasive diagnostic
      indices on Day 42 also establish predictive thresholds that can be used to
      evaluate the PHS susceptibility of large and apparently healthy male and female
      broilers.

PMID- 9776068
TI  - Reduced-fat bologna manufactured with poultry skin connective tissue gel.
AB  - The objectives of this study were to determine temperature (50, 60, 70, and 80 C)
      and time (0.5, 1.0, 1.5, and 2.0 h) effects on the water binding ability of
      chicken skin connective tissue (CCT) and its ability to form model gels; to
      develop and determine the functionality of added water (AW, 100, 200, and 300%)
      CCT gels; and to evaluate the attributes of reduced-fat bologna containing 10 to
      30% addition of 100 to 300% AW CCT gels. Determination of water binding and
      holding capacities, and objective textural and color attributes provided data
      suggesting the practicality of developing and incorporating AW CCT gels as water
      binders in reduced-fat bologna. Processing qualities, and textural and sensory
      attributes were analyzed to assess the feasibility of manufacturing a reduced-fat
      processed poultry product containing a modified poultry by-product. Heating (60
      C) CCT for 0.5 h allowed the formation of model CCT gels containing 100 to 300%
      AW. Added water decreased CCT gel fat, protein, collagen content, and hardness
      due to a protein (collagen) dilution. Hydration values were sufficient to allow
      CCT to bind up to 300% AW. Gel fragility and syneresis were observed in higher AW
      CCT gels due to protein dilution, a result of the high fat content of raw CCT
      (approximately 40%) and added water. Percentage gel addition and AW decreased (P
      < 0.05) the hardness of reduced-fat CCT gel bologna. All bologna treatments
      exhibited acceptable sensory attributes. This study indicated the feasibility of
      using lower AW CCT gels as texture-modifying agents in reduced-fat comminuted
      meat products.

PMID- 9776069
TI  - Assessment of three devices used in shear tests of cooked breast meat.
AB  - Methods that increase processing efficiency to save energy costs and to improve
      yield and volume must be evaluated in terms of maintaining or improving final
      product quality. Shear tests measure the force to cut through fibers of cooked
      samples. They are the simplest and most common tests used to document cooked meat
      texture. However, information obtained from shearing devices that perform in a
      similar way may not be interchangeable. In this study, three shearing devices
      were assessed. Eight treatments were imposed on broiler breasts processed under
      commercial conditions to represent ranges of texture characteristics. Treatments
      included electrical stimulation (S), or no stimulation (NS) of carcasses;
      postchill deboning at 2 or 6 h; and marination (M), or no marination (NM). Shear
      force values of cooked breasts were obtained from the benchtop Warner-Bratzler
      (BT-WB) machine, the Warner-Bratzler blade attachment (TA-WB) and a 45 degrees
      chisel-end blade attachment (TA-WD). The TA-WB and TA-WD were attached to Model
      TA.XT2 texture analyzer. For each device, shear value differences were
      significant (P < 0.05) for deboning time. Marination effects were significant (P
      < 0.05) for BT-WB and TA-WB. Stimulation by debone interactions were significant
      (P < 0.05) for BT-WB and TA-WD. The TA-WD values varied the greatest over all
      treatments (SD = 5.52; SE = 0.65). Variations of BT-WB and TA-WB shear values
      were similar (SD = 3.25, 2.97, respectively; SE = 0.38, 0.35).

PMID- 9776070
TI  - Topographical distribution of cells in the rat submandibular gland duct system
      with special reference to dark cells and tuft cells.
AB  - The duct system of the rat submandibular gland consists of the intercalated duct,
      the granular convoluted tubule, the striated duct, the excretory duct, the main
      excretory duct, and the salivary bladder. The duct system contains special cell
      types, such as dark cells and tuft cells, in addition to principal cells.
      However, little is known about cell distribution in the duct system. The purpose
      of the present study was to examine cell distribution and to perform a
      morphometric analysis of the duct system. Transmission and scanning electron
      microscopy were used to examine the duct system of the rat submandibular gland.
      Six regions in the duct system, the striated duct, the interlobular excretory
      duct, the 5-mm proximal excretory duct from the hilus, the main excretory duct at
      the hilus, the 10-mm distal main excretory duct from the hilus, and the salivary
      bladder, were investigated. Morphometric and statistical analyses of the data
      were then performed. The epithelium of the duct system consisted of a
      heterogeneous cell population. Dark cells and tuft cells were present throughout
      the duct system. The principal, dark, and tuft cells were distinguished by their
      different microvilli by using a scanning electron microscope. The frequency of
      these cells in the total epithelial cell population was as follows: The
      percentage of principal cells in the six regions of the duct system varied from
      87.5% to 94.4%, that of dark cells varied from 4.1% to 7.2%, and that of tuft
      cells varied from 1.8% to 7.2%. The number of principal and tuft cells was
      significantly different between the striated duct and the main excretory duct at
      the hilus (P < 0.01). However, no significant difference in number of dark cells
      throughout the duct system was observed (P > 0.05). The abundance of the
      principal, dark, and tuft cells in the duct system of the rat submandibular gland
      was determined. Few tuft cells were distributed in the striated duct, and most
      were found at the hilus. Dark cells were distributed equally throughout the duct
      system.

PMID- 9776071
TI  - Apoptosis and Bcl-2 oncoprotein expression in the human fetal central nervous
      system.
AB  - Apoptosis and the apoptosis-regulatory gene bcl-2 have been suggested from animal
      studies to be important during the development of the central nervous system
      (CNS), but information on apoptotic activities of the developing human CNS has
      been scarce. To establish spatial and temporal distributions of apoptotic cells
      and Bcl-2 oncoprotein expression, we examined sections taken from cerebral
      cortex, hippocampus and brainstem at weeks 14, 18, 27, and 32 of gestation.
      Terminal transferase-mediated nick end labelling (TUNEL), histological analyses,
      and immunocytochemical staining using monoclonal antibodies were employed. Except
      for layer I of the motor cortex and the molecular layer of the hippocampus, both
      at week 14 of gestation, TUNEL-positive cells with typical apoptotic appearance
      and apoptotic indices, ranging from 0.08 to 2.85, were found in all other brain
      regions examined including visual, sensory, frontal and motor cortices,
      hippocampus, dorsal raphe, locus coeruleus, and periaqueductal grey of the
      brainstem. No specific spatial or temporal distribution patterns of apoptotic
      cells were found in the cortices. However, the apoptotic index of the molecular
      layer of the hippocampus increased with the gestation age. The periaqueductal
      grey of the brainstem showed high apoptotic indices (ranging from 0.37 to 2.85)
      at all the gestation ages studied. An inverse correlation between apoptosis and
      Bcl-2 oncoprotein expression was found in visual, sensory, and motor cortices but
      not in the frontal cortex and hippocampus. Apoptosis and Bcl-2 oncoproteins are
      important for CNS development and, apart from being an apoptosis regulator, Bcl-2
      oncoproteins may also have other roles to play during neural development.

PMID- 9776072
TI  - Perivascular structures in corrosion casts of the human central nervous system: a
      confocal laser and scanning electron microscope study.
AB  - Scanning electron microscopy (SEM) of microvascular corrosion casts revealed
      perivascular structures that resembled smooth muscle and pericyte cells. Although
      these structures have been studied in widely different experimental contexts,
      their origin, function, and distribution pattern in different tissues are not
      understood. Microvascular corrosion casts from 15 fresh human brains and 20
      lumbar spinal cords were studied by SEM. In five cerebral hemispheres a
      fluorescent resin was injected in order to study the vascular bed by confocal
      laser scanning microscopy (CLSM). Microvascular casts showed two perivascular
      structures on their surfaces: plastic strips, which formed a muff around
      arteriolar vessels, and pericyte-like structures that were present around the
      capillary network. Their morphological characteristics and distribution were
      similar to those of smooth muscle cells and pericytes, respectively. The SEM
      study showed that these structures were not tightly joined to the cast surface,
      but were connected to the vascular cast by narrow plastic connections. The CLSM
      showed that the resin invaded the subendothelial space, thus giving rise to these
      structures. Perivascular structures associated with arteriolar and capillary
      vessels appear to represent smooth muscle cells and pericytes. They are formed by
      the passage of the resin to the subendothelial space, probably through weak
      endothelial cell junctions. The effusion of resin into the subendothelial space
      may represent evidence for the structural basis of myocyte and pericyte cell
      control. Chemical communication by substances released locally or transported to
      these cells through these junctions may regulate their functions, allowing them
      to regulate blood flow.

PMID- 9776073
TI  - Architecture of the cancellous bone of the human talus.
AB  - The trabeculae of the cancellous bone are formed along the direction of the lines
      of stresses to which a bone is subjected. The talus sustains the weight of the
      body and transmits the weight in different directions (i.e., the calcaneus and
      navicular). The aim of the present study was to investigate the architecture of
      the cancellous bone of the talus to understand the mechanism of transmission of
      force within the bone. Twenty-five dry, macerated tali of adult male humans were
      used to study the trabecular architecture. In a few bones, serial longitudinal
      (parasagittal), transverse (coronal), and horizontal sections were cut; in other
      bones, the trabecular bone was exposed by removal of cortical bone. Trabecular
      architecture was studied by dissection microscope and by taking radiographs of
      the slices. The body of the talus consisted of vertical, parallel plates arranged
      posteroanteriorly. This kind of orientation of the plates facilitates the
      transmission of weight, when the tibia rolls posteroanteriorly on the trochlear
      surface during walking. The trabecular architecture in the head of talus
      consisted of semiarched plates running parallel to each other. The vertical limb
      of these semiarched plates were situated above the middle and anterior calcaneal
      facets on the plantar surface of the head, whereas the horizontal limbs of the
      arches were deep to the navicular articular surface of the head. The vertical
      plates of the body and semiarched plates of the head were interconnected by a
      meshwork of irregularly arranged trabecular bone of the neck. The architecture of
      this meshwork was such that it could facilitate the change in the direction and
      nature of force. In conclusion, the part of compressive force, acting vertically
      downward on the body of the talus during standing, was converted to tensile force
      in the neck, and its direction was made perpendicular to enable this force to go
      toward the head of the talus. In a similar manner, the semiarched pattern of
      plates in the head facilitated the change in the direction of the force, at the
      end of the stance phase, from the downward (toward calcaneus) to the forward
      (toward navicular) direction.

PMID- 9776074
TI  - In vivo and in vitro assessment of mitogen activated protein kinase involvement
      during quail secondary palate formation.
AB  - Spatiotemporally regulated cell proliferation and differentiation are crucial for
      the successful completion of morphogenesis of the vertebrate secondary palate. An
      understanding of the mechanisms by which these cellular phenomena are regulated
      during palate development involves the identification of the various signal
      transduction pathways. In the present study, the presence and activation of
      mitogen-activated protein (MAP) kinases were investigated during the development
      of quail secondary palate. The palatal shelves were dissected on days 5-9 of
      incubation, homogenized, and centrifuged, after which the samples were separated
      by anion exchange fast protein liquid chromatography. The fractions were analyzed
      for myelin basic protein (MBP) phosphorylation. In addition, primary cultures of
      quail palate mesenchymal cells (QPMCs) were treated with epidermal growth factor
      (EGF) and prepared for MBP phosphorylation assays. A temporally regulated pattern
      of phosphotransferase activity, characterized by a three-fold increase in
      phosphotransferase activity toward MBP between days 5 and 8 of incubation, was
      observed during quail palate development. Western blotting, using MAP kinase
      antibodies, demonstrated the presence of a 42-kDa isoform between days 5 and 9 of
      incubation, during which the level of protein remained constant. Antityrosine
      immunoblotting with 4G10 also detected a 42-kDa protein. Phosphotransferase
      assays, using either a MAP kinase-specific substrate peptide (S5) or a protein
      kinase C inhibitor (R3), further confirmed the presence of a MAP kinase in the
      developing palate of quail. Because diverse biological processes occur
      concurrently during in vivo palate morphogenesis, the involvement of MAP kinase
      was explored further in primary cell culture. The data showed that EGF stimulated
      proliferation and activated 42-kDa MAP kinase in QPMCs. It is suggested that MAP
      kinase cascade may be involved in growth factor-regulated cell proliferation
      during morphogenesis of quail secondary palate.

PMID- 9776075
TI  - Scanning electron microscopic and morphometric analysis of the guinea pig uterine
      luminal surface: cyclic and ovarian steroid-induced modifications.
AB  - A morphometric and scanning electron microscopic analysis of endometrial, luminal
      topographical changes of cyclic and ovariectomized, ovarian steroid-treated
      guinea pigs was undertaken to determine the effects of cyclic endocrine
      influences on the uterine surface features recognized to be involved in the
      process of interstitial blastocyst implantation. Estrogenic stimulation of the
      uterine epithelial layer induced microvillus growth and closed the endometrial
      gland openings on the luminal surface. Progestins antagonized these parameters,
      as indicated by short, sparse microvillus formation over a flat luminal uterine
      surface on which gland openings were both numerous and prominent. The combined
      effects of estrogen and progesterone therapies induced luminal epithelial changes
      resembling those characterizing the cyclic uterine surface at the time of
      blastocyst implantation. These data indicate that the cyclic alterations in the
      uterine luminal surface are directly regulated by ovarian steroid hormones, and
      that these changes in surface structure are synchronized and directly involved in
      the preparation for blastocyst-uterine interaction during the nidatory process in
      this species.

PMID- 9776076
TI  - Ultrastructural features of odontoclasts that resorb enamel in human deciduous
      teeth prior to shedding.
AB  - Three dental hard tissues, i.e., cementum, dentin, and enamel, are resorbed by
      multinucleated cells referred to as "odontoclasts." These cells have
      morphological and functional characteristics similar to those of bone-resorbing
      osteoclasts. However, concerning enamel resorption, which is a process that may
      occur during tooth eruption, satisfactory ultrastructural data on odontoclastic
      resorption are still lacking. Ultrastructural and histochemical characteristics
      of odontoclasts resorbing enamel of human deciduous teeth prior to shedding were
      examined by means of light microscopy and transmission and scanning electron
      microscopy. Odontoclasts that that resorbed enamel were tartrate-resistant acid
      phosphatase (TRAP)-positive multinucleated giant cells that were essentially the
      same as those that resorbed dentin and cementum. Ultrastructurally, they had
      numerous mitochondria, lysosomes, and free polysomes in their cytoplasm. In
      addition, they were characteristically rich in large cytoplasmic vacuoles
      containing enamel crystals in the cytoplasm opposite the ruffled border. Although
      they extended a well-developed, ruffled border against enamel surface, a clear
      zone--an area typically devoid of organelles--was rarely seen in these cells. In
      many cases, the cells were in very close contact with the enamel surface by the
      peripheral part of their cytoplasm. The enamel prisms at the resorption surface
      contained more loosely packed and electron-lucent enamel crystals compared with
      those of unresorbed, intact enamel. Furthermore, numerous thin needle- or plate
      like enamel crystals that were liberated from the enamel matrix were found in the
      extracellular channels of the ruffled border and in various-sized cytoplasmic
      vacuoles in their cytoplasm. The superficial layer of the enamel matrix
      undergoing odontoclastic resorption stained positively with toluidine blue and
      for TRAP activity. The results of the present study suggest that odontoclasts
      resorbing enamel secrete acids as well as organic components, including
      hydrolytic enzymes, into the resorption zone underlying their ruffled border and
      that they phagocytose crystals that have been liberated from the partially
      demineralized enamel matrix by acids, subsequently dissolving them
      intracellularly.

PMID- 9776077
TI  - Preganglionic fibers in the rat hypogastric nerve project bilaterally to pelvic
      ganglia.
AB  - Stimulation of the hypogastric nerve (HGN) often evokes bilateral responses in
      some pelvic organs. Retrograde labeling studies indicate that axons of
      postganglionic neurons often cross to the opposite side. However, there is little
      information available as to whether preganglionic fibers in the HGN have a
      contralateral projection to pelvic ganglia. A retrograde tracer was injected into
      the left major pelvic ganglion (MPG) in rats receiving various lesions of
      preganglionic nerves (HGN and pelvic nerve, PN). The lumbar spinal cord was then
      examined for location and number of dye-filled neurons. In a second approach, the
      incidence of synaptophysin immunoreactivity (SN-IR) perineuronal profiles
      (baskets) was examined in the MPG and in the accessory pelvic ganglia (APG) after
      nerve lesions. Labeled neuronal profiles were found in spinal cord nuclei
      (Lumbar1-2) after dye injection of the MPG in animals with an intact
      contralateral HGN. Cutting both HGNs virtually eliminated dye labeling in the
      lumbar cord, as did severing commissural branches (CB) between pelvic ganglia
      (leaving the contralateral HGN intact). Some SN-IR baskets were found in the left
      APG when only the contralateral HGN was intact, but baskets were rare when all
      four preganglionic nerves were cut. It could not be determined whether the HGN
      projects to the contralateral MPG, since SN-IR baskets were numerous in the MPG
      even when all four nerves were cut. This study has shown that some preganglionic
      fibers in the HGN synapse on neurons in contralateral pelvic ganglia. Both the
      APG and MPG receive contralateral innervation, but it is likely that neurons in
      the APG are the primary target of this input. Thus, in addition to crossing
      postganglionic fibers, a portion of the bilateral control of pelvic tissues is
      accomplished by preganglionic fibers which target autonomic neurons in
      contralateral ganglia.

PMID- 9776078
TI  - Descending neural projections to the spinal cord in the channel catfish,
      Ictalurus punctatus.
AB  - Retrograde transport of horseradish peroxidase was used to determine the
      descending projections to the spinal cord in an otophysan fish, the channel
      catfish, Ictalurus punctatus. The majority of cells projecting to the spinal cord
      are located in the reticular formation, which is organized into rhombomeric
      segments. Vestibulospinal neurons are located in the descending, magnocellular,
      and tangential octaval nuclei, as well as in the medial octavolateralis nucleus
      of the lateral line system. Cells in the facial lobe project to the spinal cord.
      Additionally, axons of cells of the trigeminal system and the nucleus of the
      lateral lemniscus project caudally into the spinal cord. In the midbrain,
      descending spinal projections arise from cells of the medial longitudinal
      fasciculus and the red nucleus. More rostrally, cells of the ventrolateral
      thalamus, dorsal periventricular hypothalamus, central pretectal and
      magnocellular preoptic nuclei also project to the cord. The results of this study
      indicate that there are a number of homologies in the descending systems of bony
      fishes and other vertebrate taxa, including tetrapods. We also provide further
      evidence that a red nucleus is present in the brains of bony fishes and is
      therefore a primitive vertebrate character antedating the evolution of tetrapods.

PMID- 9776079
TI  - Morphology of human neutrophils: a comparison of cryofixation, routine
      gluteraldehyde fixation, and the effects of dimethyl sulfoxide.
AB  - Cell shape and density are critical to the evaluation of neutrophil function
      and/or activation. Dimethyl sulfoxide-cryofixation-freeze-substitution processing
      (DCF) instantly preserves cell processes and ultrastructural elements with fewer
      artifacts than routine chemical fixation with glutaraldehyde and postfixation
      osmium tetroxide (GO). This study morphometrically examined density-separated
      neutrophils to assess differences in DCF and GO processing procedures and studied
      the effect of dimethyl sulfoxide followed by GO fixation (DGO) on morphology.
      Fifteen consecutive neutrophils were analyzed using computerized planimetry for
      differences in DCF v. GO treatments (n = 4) and DGO v. GO treatments (n = 4).
      Cryofixed and DGO-fixed cells were significantly rounder than GO cells which had
      a more irregular surface with membrane projections. The cell volume of GO cells
      was 27-30% smaller than in DCF or DGO processing, while the surface area was
      similar. The increased volume in DCF and DGO cells did not appear to be due to
      abnormal cell swelling, since membranes, nuclear envelope, and mitochondrial
      cristae were more intact than in GO cells. Preservation of mitochondria as well
      as endocytic caveolae with a subplasmalemmal coating was best in DCF samples,
      moderate in DGO, and poorest in GO. Morphometric data showed that the nuclear
      compartment was 22% smaller, while the cytoplasm (and its associated
      compartments) was 29% smaller in GO compared to DCF-processed neutrophils. This
      was consistent with the more dense cytoplasm in GO cells. Pretreatment of
      neutrophils with dimethyl sulfoxide (DMSO) resulted in volume preservation and
      improved the morphology of GO fixation. In summary, DCF appears to be an
      excellent method for preserving neutrophil membranes and cytoplasmic organelles
      (particularly mitochondria), and prevents a number of artifacts caused by routine
      GO fixation. Morphology can also be improved by using DMSO in conjunction with
      GO.

PMID- 9776080
TI  - Fibrocartilages in the extensor tendons of the interphalangeal joints of human
      toes.
AB  - The extensor tendons of the fingers and toes form part of the capsule of the
      interphalangeal joint and press against the proximal phalanx during flexion.
      Previous work on the fingers has shown that there is a "sesamoid" fibrocartilage
      on the deep surface of each tendon that labels immunohistochemically for a
      variety of glycosaminoglycans and collagens. However, we know little about the
      molecular composition of the tendon in the toes. This question is of special
      interest, because the mechanics of the interphalangeal joints differ in the upper
      and lower limbs-the toes balance the forefoot, distribute load during the gait
      cycle, and transmit the pull of larger muscles. This means that their extensor
      tendons are more often under higher tension than those in the fingers. Here, we
      report the presence of an equivalent fibrocartilage and compare its
      immunolabelling characteristics in all the toes. Six forefeet were removed from
      elderly cadavers, and the interphalangeal (IP) joints were fixed in 90% methanol.
      The extensor tendon and its enthesis were dissected out from the IP joint of the
      big toe and from the proximal interphalangeal (PIP) joint of all lesser toes,
      decalcified, cryosectioned, and immunolabelled with a panel of monoclonal and
      polyclonal antibodies for type I, II, III, and VI collagens; chondroitin 4 and 6
      sulphates; and dermatan and keratan sulphate. Antibody binding was detected with
      the Vectastain ABC Elite avidin-biotin-peroxidase kit (Vector Laboratories,
      Burlingame, CA). The extensor tendon in all the toes had a metachromatic,
      sesamoid fibrocartilage on its deep surface that immunolabelled for all
      glycosaminoglycans and for type I, III, and VI collagens. Labelling for type II
      collagen was seen in the sesamoid fibrocartilage of all toes but was particularly
      characteristic of the 2nd through 5th toes. The immunolabelling patterns of the
      enthesis fibrocartilage were similar in all toes and to results reported
      previously for fingers. The normal occurrence of type II collagen in the sesamoid
      fibrocartilage of the 2nd through 5th toes is in contrast to our published data
      on the fingers. The finding can be related to the more constant loading of the
      tendon in the toes. The greater prominence of type II collagen in the sesamoid
      fibrocartilage of the 2nd through 5th toes could be related to a difference in
      joint position during walking between the 1st toe and the 2nd through 5th toes-
      the PIP joints of the latter are usually more flexed than the IP joint of the
      former.

PMID- 9776081
TI  - Embryogenesis of tracheal atresia.
AB  - A spectrum of tracheo-esophageal anomalies has been described in an adriamycin
      treated model with common features to the human pattern. Tracheal agenesis was
      part of this spectrum. It is a rare congenital anomaly that has not been
      described in embryos. Virgin timed-pregnant Sprague-Dawley rats were injected
      with adriamycin i.p. at a dose of 2 mg/Kg on days 6-9 of gestation (plug day =
      day 0). Fetuses were recovered at term and histologic assessment of tracheo
      esophageal anomalies was made. Also, embryos were removed on different
      gestational days and the embryology of these defects was analysed. Two out of
      sixty-two fetuses and nine out of 180 embryos were identified with tracheal
      atresia. Type III tracheal atresia was seen in the full-term fetuses with a
      tracheo-esophageal fistula arising from the origin of the left main bronchus. Day
      13 embryos did not show normal tracheal development; instead, the lung buds
      developed from the ventral aspect of the foregut which continued to the stomach
      as a lower esophageal segment. A blind ending pouch was seen on the ventral
      aspect of the upper part of the foregut. The embryogenesis of tracheal atresia
      was similar to that of esophageal atresia except that the blind upper foregut
      pouch developed ventrally rather than dorsally.

PMID- 9776082
TI  - Increasing frequency of occurrence of tuft cells in the main excretory duct
      during postnatal development of the rat submandibular gland.
AB  - Tuft cells, a widespread cell type that is present in the mucosal epithelia of
      hollow organs, including the main excretory duct (MED) epithelia of the rat
      salivary gland, are well documented morphologically. However, studies of their
      development are few. The purpose of the present study was to examine the
      perinatal and postnatal development of tuft cells in the main excretory duct of
      the rat submandibular gland. Main excretory ducts of the submandibular gland were
      obtained from five male Wistar rats at the ages of 0, 1, 7, 14, 17, 21, 23, 28,
      and 56 postnatal days and were prepared for scanning and transmission electron
      microscopy. The tuft cells, which are distinguished easily by their long
      microvilli protruding into the lumen, were recognizable first at 17 postnatal
      days. They showed a remarkable increase in number between 3 and 4 postnatal
      weeks. The percentages of tuft cells were 0.4% at 17 postnatal days and 0.8% at 3
      postnatal weeks. The number of tuft cells represented approximately 5% of the
      total epithelial cells by 4 postnatal weeks. There was a significant difference
      between 3 and 4 postnatal weeks (P < 0.01). The microvilli of the tuft cells at
      the time of weaning had almost the same width as in the adult, but they were
      shorter. Microfilaments extending from the tips of the microvilli and
      microtubules and many electron-lucent vesicles in the supranuclear cytoplasm also
      were observed. These results indicate that tuft cells appeared in the MED of the
      submandibular gland during weaning and had abundant vesicles in their apical
      cytoplasm.

PMID- 9776083
TI  - Codistribution of procathepsin B and mature cathepsin B forms in human prostate
      tumors detected by confocal and immunofluorescence microscopy.
AB  - Cathepsin B (CB) is involved in invasion and metastasis of a variety of solid
      organ tumors, including human prostate cancer. The tertiary structures of the
      proenzyme and mature forms of CB are related closely, as revealed by
      crystallographic studies. However, the cellular distributions of the CB forms
      have not been defined in human prostate and its tumors. Our objective was to
      investigate the distribution and codistribution of CB and procathepsin B (proCB)
      in human prostate tumors. Human prostate tissue samples that were obtained from
      21 prostatectomy and/or cystectomy patients were collected immediately after
      surgery and processed for this study. We used a rabbit antihuman liver CB
      immunoglobulin G (IgG) that recognizes both mature CB and proCB and a mouse
      antipropeptide monoclonal antibody IgG that recognizes only proCB. Fluorescein
      isothiocyanate (FITC)-conjugated donkey antirabbit IgG and indocarbocyanine (Cy3;
      rhodamine)-conjugated donkey antimouse IgG were used to differentiate
      localization of the enzyme forms. Immunofluorescence of FITC and Cy3 was examined
      in prostate sections by using epifluorescence and confocal laser-scanning
      microscopy. Because fluorescence is dependent on section thickness, time needed
      for study and photography, and the antigenic sites of proCB and mature CB
      localized by antibodies and by fluorescent markers (Cy3 vs. FITC), the cellular
      distributions and the relative intensity of fluorescence on cryostat sections
      were assessed qualitatively. Immunofluorescence of Cy3 for localizing proCB and
      of FITC for localizing mature CB were observed in prostatic epithelial cells and
      their tumors and in stromal connective tissue cells. By using confocal
      microscopy, colocalization of the enzyme forms in the same cells was indicated by
      yellow fluorescence. In stromal cells (such as smooth muscles, fibroblast, and
      macrophages), the distribution of proCB and relative fluorescence intensity was
      moderate to predominant in human prostate and its tumors. In neoplastic prostate,
      the cellular distributions of CB ranged from low to predominant levels. In some
      neoplastic glands, Cy3 fluorescence for proCB was absent, whereas the mature form
      of CB localized in cancer cells and in the subjacent extracellular matrix.
      Confocal microscopy showed a close association of CB with extracellular matrix
      surrounding neoplastic acini and invasive cells, indicating that the enzyme form
      was probably involved in degradation of the matrix proteins. The negative control
      study showed no specific immunofluorescence for proCB or CB in prostate cancer
      cases. We have shown a differential distribution of proenzyme and mature forms of
      CB in normal prostate, benign prostatic hyperplasia, and neoplastic prostate. The
      enzyme forms were assessed by determining the cellular distributions of CB and
      proCB. Our study indicates that the differential distribution of proCB and CB
      might provide clues into aggressiveness of prostate cancers within Gleason
      grades. However, we emphasize that our observation should be evaluated in a
      larger series of prostate samples before a definitive conclusion can be reached.
      This is the first report to show codistribution of proenzyme and mature forms of
      CB by using confocal microscopy.

PMID- 9776084
TI  - An unusual parotid gland in the tent-building bat, Uroderma bilobatum: possible
      correlation of interspecific ultrastructural differences with differences in
      salivary pH and buffering capacity.
AB  - The tent-building bat, Uroderma bilobatum, is a small, frugivorous phyllostomid
      bat with a broad neotropical distribution. Generally found in humid forest, this
      bat lives in small groups that create daytime "roosts" from large leaves of a
      variety of tropical plants. Fruit eating engenders a variety of ecological and
      physiological challenges for bats, some of which could require adaptive features
      in their salivary glands. The parotid salivary glands of Uroderma bilobatum were
      prepared for transmission electron microscopy by using methods that have become
      standard for field work. The parotid gland is extremely unusual in structure.
      Although the secretory endpieces still produce serous granules with a complex
      substructure, they are modified into quasi striated ducts. Their basal folds,
      which are extensive, occasionally harbor some vertically oriented mitochondria,
      imparting a resemblance to striated ducts. Other evidence for the endpiece origin
      of these parenchymal components is a well-developed system of intercellular
      canaliculi, structures that never occur in bona fide striated ducts. The long but
      sparse intercalated ducts consist of two types of cells, each of which elaborates
      a modest number of secretory granules of differing substructure. Striated ducts
      are of conventional morphology, except that a few dark cells shaped like wine
      glasses are present in their walls. The striated duct cells produce no secretory
      granules, but their apical cytoplasm may contain some small, empty vesicles.
      Capillaries lie in longitudinal grooves in the base of the duct cells, an
      arrangement that might enhance electrolyte exchange. Excretory ducts consist of
      simple cuboidal epithelium composed of cytologically unspecialized cells that
      sometimes includes a dark cell. It was concluded that salivary glands could have
      a major role in adapting species to acquire nutrients from marginal sources, such
      as tropical fruits, which have a low protein and sodium content. The unusual
      parotid acinar cells in Uroderma bilobatum are discussed in the context of
      salivary pH and buffering capacity. Comparisons are made with four other bat
      species, including an insectivorous species with a salivary pH > 8.0 and a very
      high buffering capacity, an intermediate species, and a fruit bat with acidic
      stimulated saliva and very low buffering capability. Such interspecific
      comparisons provide a foundation for hypothesizing that ultrastructural features
      of the acinar cell basolateral membranes and intercellular canaliculi correlate
      with differences involving Na/H+ exchangers and release of HCO3- and, thus, are
      associated with the species differences that are important to diet and nutrient
      acquisition.

PMID- 9776085
TI  - Fine structure of three types of olfactory organs in Xenopus laevis.
AB  - There is no report on the fine structure of three types of olfactory organs in
      Xenopus laevis. Their functional assignments in olfaction are not yet
      established. The fine structure of three types of olfactory organs, olfactory
      epithelium (OE), vomeronasal organ (VNO), and middle chamber epithelium (MCE),
      was examined in Xenopus laevis by light and electron microscopy. The olfactory
      cells of the OE and the sensory cells of the VNO were equipped with cilia and
      microvilli, respectively, similar to terrestrial animals that possess both the OE
      and the VNO. On the other hand, the sensory cells of the MCE were classified into
      two types, the sensory cells with cilia and the sensory cells with microvilli,
      like those of the OE in fish. These findings suggest that the OE and the VNO in
      Xenopus laevis detect different kinds of odoriferous molecules in air, whereas
      the MCE is involved in the perception of odorants in water.

PMID- 9776086
TI  - Regeneration and myogenic cell proliferation correlate with taurine levels in
      dystrophin- and MyoD-deficient muscles.
AB  - This study coupled proton magnetic resonance spectroscopy (1H-NMR) and in situ
      hybridization plus autoradiography in a novel examination of different phenotypes
      of adult myogenesis that arise from genetic disruptions in mice. Study of muscle
      extracts from normal and dystrophin-deficient mdx limb and diaphragm muscles
      confirmed our previous findings linking taurine and muscle regeneration at the
      peak of damage and repair. 1H-NMR distinguished biochemical differences in
      regenerating muscles that were consistent with the extent of repair in three
      strains: mdx dystrophic mice; MyoD(-/-) mice that lack expression of the early
      myogenic regulatory gene MyoD; and a double-mutant mdx:MyoD(-/-) strain lacking
      expression of both MyoD and dystrophin. We tested the hypothesis that differences
      in spectra according to genotype and the regeneration phenotype are related
      specifically to proliferation by committed myogenic precursor cells. 1H-NMR
      distinguished the three mutant strains: Taurine was highest in mdx muscles, with
      the phenotype of most effective regeneration; lowest in MyoD(-/-) muscles, with
      the least effective formation of new muscle in repair, as reported previously;
      and intermediate in double-mutant muscles, now reported to show an intermediate
      repair phenotype. The early and late muscle precursors (mpcs) expressing myf5 and
      myogenin were examined for proliferation. Eighteen percent of mdx myf5-positive
      mpcs were proliferative, whereas myf5-positive mpcs did not proliferate in
      regenerating muscles that lacked MyoD expression. By contrast, whereas 30% of
      myogenin-positive mpcs were proliferative in mdx muscles, almost none were
      proliferative in MyoD(-/-) muscles, and 12% were proliferative in double-mutant
      muscles. Therefore, the extent of accumulated structural regeneration, taurine
      levels, and proliferation of late mpc (expressing myogenin) were congruent across
      genotypes. Proliferation by early mpc (expressing myf5) was inhibited by the lack
      of MyoD expression during muscle regeneration. These studies indicate the
      potential for 1H-NMR monitoring of muscle status in disease, regeneration, and
      treatment.

PMID- 9776087
TI  - Burns of the hand and upper limb--a review.
AB  - This review article addresses the principles and controversies associated with
      thermal injury to the hand and upper limb. Accepted principles are outlined and
      areas of controversy are discussed in a balanced manner. The importance of hand
      burns is described functionally and epidemiologically. Burns appropriate to
      outpatient care are defined and treatment discussed, including debridement,
      topical therapy, rehabilitation and follow-up. The general principles of
      inpatient management are given, including the controversial issue to timing of
      surgery and treatment of the exposed tendon or joint. The extent of surgery,
      methods of wound closure and difficult problem of palm burns are also discussed.
      Reconstructive principles are outlined and a problem oriented approach to the
      most common reconstructive problems given.

PMID- 9776088
TI  - Evaluation of proteinase inhibitors and free radical inhibitors/scavengers in
      reducing post-thaw viability loss of cryopreserved skin.
AB  - Cryopreserved skin must be used immediately after thawing or discarded owing to
      rapid post-thaw deterioration in viability. This is inconvenient and wasteful.
      The purpose of this study was to evaluate whether release of protease enzymes
      from cryogenically damaged cells or the action of free radicals on skin cells, is
      the cause of this deterioration. Following thawing. skin was incubated for 24 h
      at 4 degrees C in a range of protease inhibitors and free radical
      inhibitors/scavengers. The rate of deterioration was significantly reduced by
      using complex treatments including addition of serum, egg white and raised pH.
      These treatments are known to inhibit various groups of protease enzymes but
      would clearly have additional effects on the cells. Of the remaining treatments
      most of the specific protease inhibitors improved viability although not
      significantly. Treatments designed to inhibit or scavenge free radicals had
      little or no effect.

PMID- 9776089
TI  - Plasma levels of type II phospholipase A2 and nitrite/nitrate in patients with
      burns.
AB  - Type II phospholipase A2 (type II PLA2), nitrite/nitrate (NOx), tumor necrosis
      factor-alpha (TNF-alpha) and endotoxin were studied in burn patients. Type II
      PLA2 values and NOx values were both significantly higher in the group that died,
      the group with shock as a complication and the group with multiple organ
      dysfunction syndrome (MODS) as a complication, than in the group that survived,
      the group without shock as a complication and the group without MODS as a
      complication, respectively. The results suggested that type II PLA2 and nitric
      oxide (NO) may play a major role in the pathology of burn patients. Significant
      correlations were found between TNF-alpha and type II PLA2 values and between
      type II PLA2 and NOx values, suggesting the possibility of involvement in each
      other's production.

PMID- 9776090
TI  - The effect of early burn wound excision on regional gastric blood flow in rats.
AB  - This study examined the effects of early burn wound excision on gastric blood
      flow and on morphologic changes in mucosal vessels. Wistar rats were given a 30%
      total body surface area burn and divided into four groups, consisting of control
      animals (group 1), animals with burn injury without and with fluid resuscitation
      (groups 2 and 3, respectively), and animals with both fluid resuscitation and
      early wound excision (group 4). Gastric mucosal blood flow (GMBF) was measured by
      the hydrogen gas clearance method up to 24 h post-burn. Morphologic changes in
      mucosal vessels were examined by scanning electron microscopy (SEM) at 3 and 24 h
      post-burn. The GMBF sharply decreased in the acute period after the burn. In
      group 4, however, it recovered to the initial value by 6 h post-burn and there
      was no significant change throughout the experiment. Morphologically, although
      the mucosal capillaries revealed some changes such as irregularity in diameter in
      groups 2-4 at 3 h, most of mucosal capillaries retained their original appearance
      in group 4 at 24 h post-burn. These result suggest that early excision does not
      aggravate the state of gastric ischemia.

PMID- 9776091
TI  - Detection of capillary protein leakage by glucose and indocyanine green dilutions
      during the early post-burn period.
AB  - Overestimation of the plasma volume determined by the indocyanine green (ICG)
      dilution method (PV-ICG) may occur after burns, since this dye has the potential
      of extravasation in the presence of the capillary protein leakage. Assuming that
      the initial distribution volume of glucose (IDVG) consistently indicates the
      extracellular fluid volume of highly perfused organs including plasma,
      overestimation of the PV-ICG can be detected by a higher PV-ICG/IDVG ratio. The
      present study was designed to test whether a higher PV-ICG/IDVG ratio is observed
      within 24 h post-burn compared to the subsequent days. Ten severely burned adult
      patients admitted to the ICU were studied through the 2nd post-burn day. The
      daily IDVG and PV-ICG were calculated using a one compartment model by
      simultaneous administration of glucose, 5 g, and ICG, 25 mg. Although the IDVG
      increased on the 1st post-burn day (p < 0.05), the PV-ICG remained unchanged. The
      PV-ICG/IDVG ratio within 24 h post-burn was significantly higher than that on the
      1st post-burn day (p < 0.01). Results indicate that overestimation of the PV-ICG
      can occur within 24 h post-burn and suggest that simultaneous measurement of the
      IDVG and the PV-ICG would help predict the generalized capillary protein leakage
      after burns.

PMID- 9776092
TI  - The efficacy of trypsin: chymotrypsin preparation in the reduction of oxidative
      damage during burn injury.
AB  - This study was mainly aimed to investigate the efficacy of trypsin:chymotrypsin
      to elicit anti-oxidant properties. In our earlier studies it was observed that
      the enzyme preparation exhibited an anti-inflammatory action as there was a
      remarkable reduction in oedema formation and tissue destruction. This led to
      further study on the amount of lipid peroxidation products formed and the levels
      of enzymatic and non-enzymatic anti-oxidants and relative trace element contents
      of copper, selenium, iron and zinc during administration of the enzyme
      preparation. Decreased formation of lipid peroxidation products was observed in
      treated group in comparison with the untreated group. Higher levels of enzymatic
      anti-oxidants mainly super oxide dismutase, catalase, glutathione peroxidase and
      glutathione-s-transferase and non-enzymatic antioxidant namely ceruloplasmin
      persisted for a longer period of time in the treated group than in the untreated
      group. No statistical significance was observed in non-enzymatic antioxidants
      viz. ascorbic acid and tocopherol levels in both the groups. Increased serum
      copper and selenium levels in the treated group could be related to higher levels
      of the ceruloplasmin and glutathione peroxidase observed in the treated group.
      The above studies support the finding that treatment with the enzyme preparation
      reduced tissue destruction leading to decreased formation of free radicals and
      subsequent effective scavenging of free radicals by the higher levels of
      enzymatic and non-enzymatic anti-oxidants.

PMID- 9776093
TI  - Results of a survey on the use of different treatment options for partial and
      full thickness burns.
AB  - 36 Key opinion leaders in the field of burn care from countries all over the
      world participated in a survey on their preferences for ways of treating
      different types of burns. The article describes the results of the survey and
      analyses the different treatment preferences.

PMID- 9776094
TI  - Non-accidental burns in children.
AB  - A retrospective review of five hundred and seven consecutive admissions to a
      state-wide paediatric burns unit over a three year period was made to assess the
      characteristics of the burn injuries and to see which, if any, characteristics
      would help to distinguish accidental burns from burns which were due to abuse or
      neglect. In 86% of admissions (the 'accident group') it was considered that the
      injury was accidental, with no evidence of deliberate injury or gross neglect.
      Eight percent of admissions (the 'abuse/neglect group') were referred to the
      State Department of Community Services for abuse or neglect resulting in the
      Department becoming involved in the family's management. In six percent of cases
      (the 'concern group') the Unit had concerns that the family's emotional or social
      situation was a significant factor in the child's injury, or made further injury
      more likely, and discussed the family's situation with the Department, but formal
      intervention was not undertaken by the Department. There were no differences
      between the groups in age or mortality. Children in the 'abuse/neglect' and the
      'concern' groups were more likely to require skin grafting and treatment in the
      intensive care unit. They were more likely to come from single parent families
      and were more likely to have burns involving both hands or both legs. There were
      few other distinguishing factors. The incidence of prior notification for abuse
      and neglect was four percent for the 'accident' group, 14% for the 'concern'
      group and 46% for the 'abuse/neglect' group. This is considerably higher in the
      'concern' and 'abuse/neglect' groups than the annual state incidence of 1.73% for
      abuse and neglect notifications. While the clinical features of a burn may often
      not be helpful in reaching a diagnosis of abuse or neglect as a cause of the
      burn, it appears that many children who have non-accidental burns have also had
      prior notifications for other types of abuse or neglect.

PMID- 9776096
TI  - Extracorporeal membrane oxygenation in the treatment of inhalation injuries.
AB  - Smoke inhalation is a leading cause of death in burns patients. Conventional
      ventilation cannot always maintain adequate tissue oxygenation. Extracorporeal
      membrane oxygenation (ECMO) has rarely been used in the treatment of smoke
      inhalation injuries. ECMO is a proven therapy in severe neonatal respiratory
      failure and has also been used to good effect in the treatment of children and
      adults. We report the cases of two children who developed severe respiratory
      failure refractory to maximal ventilation, one case followed smoke inhalation
      alone, the other followed smoke inhalation and burns. Pre-ECMO PaO2/FIO2 ratios
      were 6.5 and 8 kPa, respectively. The patients were treated with veno venous ECMO
      for 72 and 144 h, respectively. The use of ECMO for respiratory failure due to
      smoke inhalation and thermal injury is discussed.

PMID- 9776095
TI  - Recreational-outdoor burns: the impact and severity--a retrospective review of
      107 patients.
AB  - INTRODUCTION: Campfires, bonfires and barbecues play a prominent role in outdoor
      activities and serve a variety of decorative and functional purposes. Given all
      of it's various forms, uses and benefits, the outdoor fire can turn dangerous in
      a matter of seconds: a stumble or fall (the child running that trips) leads to
      direct contact with the flames and subsequent burn injury. With it's everyday
      occurrence, we were surprised to find a paucity of information regarding this
      type of burn in the literature, including the NBIE analysis. METHODS: A
      retrospective review of 107 patients admitted to the Maricopa Medical Bum Center,
      from 1987 to 1996, was conducted. Each chart was analyzed for the patient
      demographics, mechanism of injury, percent total body surface area burned,
      operative versus non-operative treatment and overall outcome. RESULTS: An average
      burn injury involved 5.7% TBSA, with a wide range from 1 to 47%. The majority of
      our population involved either small children or intoxicated adults and a total
      of 50 patients required 92 operations. Severe morbidity, including 4 amputations
      and 2 mortalities, were seen. The average hospital stay was 14.3 days, ranging
      from 1 to 52 days. CONCLUSIONS: Recreational outdoor burns were extremely common
      injuries leading to loss of functional employment and prolonged physical therapy
      requirements. Small children and intoxicated adults comprised the majority of our
      study population. The impact and severity of such outdoor fires could be greatly
      affected by appropriate attention to prevention.

PMID- 9776097
TI  - Successful utilization of ECMO to treat an adult burn patient with ARDS.
AB  - We present an interesting case of the first adult reported in the United States
      to suffer from thermal burns, adult respiratory distress syndrome (ARDS) and to
      be treated with extracorporeal membrane oxygenation (ECMO) who survived. Our
      patient is a 26 year old male who sustained thermal burns (12% TBSA) to his face
      and anterior trunk and broncoscopically demonstrable inhalation injury. He was
      transported to our regional burn center for burn wound care and ventilatory
      support. The patient was treated with silver sulfadiazine 1% to his wounds which
      healed per primam. Because of low oxygen saturation he required increasing FIO2.
      The following parameters: FIO2= 1, PEEP = 17, minute ventilation of 15.1 1, peak
      airway pressure of 45 and mean of 27, along with chest X-rays corroborated the
      severity of ARDS. The patient failed volume control ventilation. A trial of
      pressure ventilation was attempted but the patient only reached O2 saturation in
      the low 80s. At this point, the decision was made to transfer the patient to a
      hospital capable of ECMO treatment. The patient was subsequently treated with
      veno venous ECMO. Six weeks later the patient was discharged from the hospital
      off all ventilatory support.

PMID- 9776098
TI  - Deep electrical burns of the calvarium: early or delayed reconstruction?
AB  - Three cases of deep high-energy electrical burns of the calvarium are presented.
      Surgical aspects such as the timing of osteonecrectomy, reconstruction and the
      choice of methods for covering of extensively denuded brain are discussed.

PMID- 9776099
TI  - Neuroleptic malignant syndrome in a burn patient.
AB  - A 39 year old white male with a 55% total body surface burn who developed
      neuroleptic malignant syndrome (NMS) during his acute course is reported. The
      patient had several acute sinusitis and septic episodes during his acute course.
      On postburn day 31, he developed a temperature of 108.4 degrees F (42.4 degrees
      C). This responded promptly to Dantrolene and Bromocriptene. His recovery was
      uneventful. NMS is a drug-related response to various medications, such as
      Haloperidol, which the patient was receiving. NMS must be considered as part of
      the differential diagnosis of fever in burn patients receiving medication known
      to cause the syndrome.

PMID- 9776100
TI  - Correction of post burns contracture of wrist with Ilizarov method.
AB  - A case of severe post burns contracture of the wrist, of 43 years duration
      resulting in recurrent ulceration of the skin was successfully treated by gradual
      distraction using the Ilizarov method. This method is superior to plaster of
      Paris cast and is more versatile than other forms of external fixation.

PMID- 9776101
TI  - Burn injuries following explosion of car heaters.
AB  - We report four cases of burn injuries inflicted by hot coolant after the
      explosion of the heating unit in four motor-vehicles of the same make and
      version, in similar circumstances while the patients were driving their cars.
      Burns of this type can cause considerable morbidity with an accompanying high
      risk of a traffic accident.

PMID- 9776102
TI  - Burns in a suicide attempt related to psychiatric side effects of interferon.
AB  - A 50-year-old woman was admitted to our critical care center after pouring lamp
      oil on herself and setting herself on fire. Diagnosed with chronic hepatitis, she
      had received interferon-alpha at another hospital. During interferon therapy she
      developed anxiety, irritability, sleeplessness, and depression. At our hospital
      she underwent fluid resuscitation according to the method of Baxter. After
      treatment with topical cream and ointment, she underwent skin grafting.
      Interferon was not given. After discharge, wound healing proved satisfactory. She
      was intelligent and insightful, and her mental condition remained stable with no
      apparent emotional problems. As she had no significant past medical or
      psychiatric history and no history of substance abuse, we believe that her
      depression was a side effect of interferon therapy. A number of reports have
      described depression and other psychiatric disorders associated with interferon,
      but none of these accounts have concerned burns sustained in suicide attempts.
      This case underscores the potential seriousness of adverse reactions to
      interferon characterized by emotional disturbance and also illustrates that
      physicians who treat burn patients need to have an understanding of affective
      disorders and unusual side effects of medication.

PMID- 9776104
TI  - Egg on your face.

PMID- 9776103
TI  - Increasing numbers of patients with self-inflicted burns at Dutch burn units.

PMID- 9776105
TI  - Recent references.

PMID- 9776106
TI  - Rheumatoid arthritis, fasting, diet and bacteria: myths and enthusiasm.

PMID- 9776107
TI  - Urinary excretion of the pyridinium cross-links of collagen in systemic lupus
      erythematosus.
AB  - The aim of this study was to measure the urinary excretion of the pyridinium
      cross-links of collagen and to determine their usefulness as markers of reduced
      bone mineral density in systemic lupus erythematosus (SLE). All female SLE
      patients managed at a single centre were invited to participate in a cross
      sectional study of urinary pyridinium cross-links excretion (HPLC), bone mineral
      density (DXA), and SLE-related variables. Ninety-one women with SLE were studied,
      35 of whom were postmenopausal. Pyridinoline/Creatinine (Pyd/Cr) and
      deoxypyridinoline/Cr (Dpd/Cr) levels in postmenopausal women were significantly
      increased compared with premenopausal values (p = 0.010 and p = 0.004,
      respectively). Univariate linear regression analysis revealed a significant
      association of Dpd/Cr with reduced femoral neck and lumbar spine BMD (p = 0.001,
      p<0.001), and of Pyd/Cr with reduced femoral neck BMD (p = 0.020). In addition,
      the association of Pyd/Cr with reduced lumbar spine BMD approached significance
      (p = 0.055). Stepwise multiple linear regression analysis adjusting for other
      variables confirmed a significant association of Dpd/Cr with reduced lumbar spine
      BMD (p = 0.006), and a significant association of both Pyd/Cr and Dpd/Cr with
      postmenopausal status (p = 0.003, p<0.001). It was concluded that in this SLE
      population, the urinary excretion of Dpd/Cr was a useful marker of reduced BMD at
      the lumbar spine. Menopausal status was a major predictor of cross-links
      excretion in SLE.

PMID- 9776108
TI  - Efficacy of radiosynovectomy of the knee in rheumatoid arthritis: evaluation with
      magnetic resonance imaging.
AB  - The intra-articular injection of a radiopharmaceutical agent (radiosynovectomy)
      produces a reduction of the synovial inflammatory process. The inflammed synovial
      membrane can be identified with magnetic resonance imaging after the intravenous
      administration of gadolinium (MRI-Gd). A 6-month prospective study was carried
      out in 10 patients with rheumatoid arthritis after radiosynovectomy of the knee.
      The efficacy was evaluated with clinical parameters and MRI-Gd. A progressive
      amelioration of synovial effusion, pain, articular range of mobility, total
      leucocytes count in synovial fluid and synovial membrane thickness through MRI-Gd
      was observed. The global efficacy was considered to be good in six patients, fair
      in three and bad in one. The study shows for the first time that MRI-Gd allows
      the evaluation of the response of the synovial membrane to radiosynovectomy.

PMID- 9776109
TI  - Salmonella septic arthritis in systemic lupus erythematosus and other systemic
      diseases.
AB  - Salmonella infection is an important problem in immunocompromised patients. The
      synovium is a particular metastatic focus of Salmonella infection and can result
      in many disabilities of life. Systemic lupus erythematosus (SLE) patients were
      highly susceptible to Salmonella infection. In the past 6 years, 41 patients with
      Salmonella septic arthritis have been treated in our hospital. Eleven patients
      had an underlying systemic disease of SLE which presented with a distinctive
      clinical course. Alcoholic liver disease (six cases) was another common
      underlying systemic disease. The most frequent predisposing articular factor was
      avascular necrosis (16 cases). The hip joint was the most commonly involved site.
      Salmonella group B was the most common serotype (30/41). Seventy-three per cent
      (8/11) of the SLE group had involvement of two or more joints compared with only
      three out of 30 patients in the non-SLE group. The sex differentiation shows a
      predominance of young females (10/11) in the SLE group and middle-aged males in
      the non-SLE group. Moreover, in the SLE group, all 11 patients shared the risk of
      lupus nephritis and steroid use. Ten patients had Salmonella group B bacteraemia
      and five had urinary tract infections simultaneously. In the non-SLE group, there
      were 10 patients with a history of steroid use, three with antecedent enteritis,
      12 with bacteraemia, and three with necrotising fasciitis. Seven patients in each
      of the groups had a recurrent course. However, three patients in the non-SLE
      group had died during the episode of septic arthritis.

PMID- 9776110
TI  - Study of pro-inflammatory (TNF-alpha, IL-1alpha, IL-6) and T-cell-derived (IL-2,
      IL-4) cytokines in plasma and synovial fluid of patients with juvenile chronic
      arthritis: correlations with clinical and laboratory parameters.
AB  - Acute phase proteins, synovial fluid (SF) cellular infiltrates, pro-inflammatory
      (TNF-alpha, IL-1alpha, IL-6) and Th1 (IL-2) and Th2 (IL-4) derived cytokine
      levels both in plasma and SF were examined in pauciarticular and polyarticular
      juvenile chronic arthritis (JCA) patients during the active (n = 22) and inactive
      (n = 14) period in order to determine pathogenic mechanisms and correlations
      between cytokines and laboratory parameters showing disease activity. The
      erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) and IgG
      concentrations were found to be significantly elevated in the active period of
      JCA. In pauciarticular JCA patients, when compared with their peripheral blood
      lymphocyte subpopulations, SF CD3+ cells (73.1%) and HLA-DR+ active T cells
      (22.5%) were found to be significantly increased. In the active period of JCA,
      plasma TNF-alpha and IL-6 concentrations were significantly elevated. Plasma IL-2
      and IL-4 levels were not elevated and were found to be similar to those in the
      inactive phase and in healthy controls. SF IL-6, TNF-alpha and IL-1alpha levels
      were extremely high in all the patients. SF IL-4 and IL-2 levels were all
      undetectable. There was a significant correlation between ESR values and plasma
      IL-6 levels and between serum CRP levels and plasma IL-6 and TNF-alpha
      concentrations. In conclusion, increased local production of pro-inflammatory
      cytokines appears to account for the articular manifestations of JCA. The
      impaired production of anti-inflammatory Th2-derived cytokines (IL-4) seems to
      cause increased production of inflammatory cytokines acting on the balance
      between them. The deficit in IL-2 production was not suggested to be primarily
      involved in the pathogenesis. In addition, not only CRP and ESR values, but also
      plasma IL-6 and TNF-alpha concentrations may be used as markers of disease
      activity.

PMID- 9776111
TI  - Significance of stem cell factor and soluble KIT in patients with systemic lupus
      erythematosus.
AB  - To determine the significance of stem cell factor (SCF) and soluble KIT (sKIT) in
      the serum of patients with systemic lupus erythematosus (SLE), levels of SCF and
      sKIT in patients with SLE were estimated, and their correlations with clinical
      parameters were examined. The sKIT levels in SLE patients (n = 106) were
      significantly lower than those in healthy controls (n = 40). A significant
      negative correlation was found between the SCF and sKIT levels of SLE patients.
      Although the SCF levels correlated with the titre of anti-RNP antibody, no
      significant relationship was found between SCF levels and blood cell counts, such
      as white blood cell, red blood cell and platelet counts. sKIT levels were
      significantly correlated with the platelet count, and were negatively correlated
      with the white blood cell count, titre of anti-DNA antibody, and SLE activity
      index (SLEDAI). sKIT levels were also negatively affected by high doses of
      corticosteroid. These results indicate that serum sKIT levels may be more closely
      related than SCF to the haematological abnormalities in SLE patients, and may
      reflect the clinical status of SLE patients and the effectiveness of high-dose
      corticosteroid treatment.

PMID- 9776112
TI  - Usage of complementary therapies in rheumatology: a systematic review.
AB  - Complementary medicine (CM) is more popular than ever before. Rheumatology
      patients seem particularly keen to try CM. In this paper, surveys on rheumatology
      patients' use of CM are reviewed. The issues of perceived effectiveness, safety
      and costs are also addressed. In addition surveys of doctors' attitudes towards
      CM in rheumatology are summarised. Fourteen surveys on patients' use of CM and
      three on patients' attitudes towards CM were found and analysed. The results
      imply that the prevalence of CM varies between 30% and nearly 100%. Overall,
      patients perceive CM as being moderately effective. The survey contains only few
      data on adverse events of CM as perceived by these patients; collectively they
      suggest that adverse events are uncommon. Data on costs are similarly sparse;
      they imply that expenditure for CM is rarely high. Physicians seem to be more
      sceptical about CM than are their patients. It is concluded that, on average, CM
      is frequently used by rheumatology patients. The patients' level of satisfaction
      with CM is often considerable and few adverse effects are being reported. On the
      basis of these findings, a rigorous investigation of the effectiveness, safety
      and costs of CM in rheumatology seems desirable.

PMID- 9776113
TI  - What counselling do patients with ankylosing spondylitis receive? Results of a
      questionnaire survey.
AB  - This questionnaire survey of 71 patients with ankylosing spondylitis (members of
      the National Ankylosing Spondylitis Society of the UK) revealed that a
      substantial proportion of patients were apparently not told of several aspects of
      their illness by their doctors such as likely cause(s), familial clustering, role
      of HLA tissue typing and diet (appropriately). Only a small percentage (4.2%)
      were counselled to actively seek screening for close family members. As HLA B27
      presence is not diagnostic of ankylosing spondylitis, and it cannot be prevented
      or arrested even if diagnosed at onset or early stages, routine screening of
      close family members cannot be justified at present.

PMID- 9776114
TI  - Low frequency of HLA-B27 and scarcity of ankylosing spondylitis in a Zairean
      Bantu population.
AB  - Ankylosing spondylitis (AS) is an inflammatory rheumatic disease which is thought
      to be rarely seen in African Blacks. Its genetic predisposition has been stressed
      in Caucasians where the HLA-B27 antigen is firmly linked to the disease. In the
      present study, HLA-B27 antigen was determined in 146 individuals of Bantu root.
      Only one of these subjects was found to possess HLA-B27 antigen. This study
      correlates the low frequency of HLA-B27 with the observed scarcity of AS in
      patients attending a clinic in Kinshasa for osteoarticular diseases.

PMID- 9776115
TI  - Serum interleukin-2 receptor for the early diagnosis of rheumatoid arthritis.
AB  - The value of measuring soluble interleukin-2 receptor (sIL-2R) in the sera of
      patients with joint pain as a predicting parameter for the future development of
      rheumatoid arthritis (RA) was examined. sIL-2R was measured by the ELISA method.
      Sixty-four patients with joint pain (suspected RA: sus-RA) but no bone or joint
      destruction were enrolled over 2 years and 47 were selected for the study. Eleven
      patients whose diagnosis was sus-RA after a year of observation were successively
      followed-up for 5 years. Two-thirds of the patients whose sIL-2R levels were
      higher than those of normal healthy adults (< 82 pmol/l; mean +2SD) developed RA
      within a year. On the other hand, one-quarter of the patients with normal levels
      of sIL-2R also developed RA within a year. The presence of two or three of the
      following three items in patients with joint pain without any bone and joint
      destruction was thus indicated to be useful for the early diagnosis of RA:
      elevated CRP level (> or = 1.0 mg/dl), positive rheumatoid factor (RF) (> or = 30
      IU/ml) and an elevated sIL-2R level (> or = 100 pmol/l). Sensitivity and
      specificity were 72.7% and 96.0%, respectively. The probability of development of
      RA is expressed as P = 1/[1 + exp(2.673 - 0.01784 x sIL-2R - 0.4398 x CRP -
      0.004835 x RF)], with R2 = 0.3083 and p<0.0005. On the other hand, the sIL-2R
      levels did not correlate with any future bone or joint changes within a year of
      observation. The above criteria may therefore hopefully justify the early
      treatment of patients with joint pain using drugs that can modify the patients'
      immune function. However, the validity of these criteria still need to be
      examined more thoroughly in the future.

PMID- 9776117
TI  - Results of the Kudo elbow prosthesis in patients with rheumatoid arthritis: a
      preliminary report.
AB  - Sixteen elbows in 15 rheumatoid arthritis patients had a total elbow replacement
      with insertion of a non-constrained surface-replacement prosthesis. One patient
      died of an unrelated cause, but all the others were available for follow-up (mean
      follow-up period: 35.4 months). The results were graded according to a modified
      version of the Morrey elbow score. A good result was seen in 13 elbows and a fair
      result in two. One infection occurred, which was cured with intravenous
      antibiotics and maintenance of the prosthesis in place; however, recurrent
      dislocation persisted. Another patient had postoperative instability with
      recurrent subluxations. Eleven patients were very satisfied and one was
      satisfied. The total active range of motion increased significantly from 70.3
      degrees (SD 29.6) to 97.0 degrees (SD 15.4), mainly by increased flexion. The
      modified Morrey score increased significantly from 32.7 (SD 13.1) to 89.3 (SD
      10.3). Pain decreased from severe (n = 12) and moderate (n = 3) preoperatively to
      mild (n = 5) and absent (n = 10) postoperatively.

PMID- 9776118
TI  - Granulomatous amoebic encephalitis caused by Acanthamoeba in a patient with
      systemic lupus erythematosus.
AB  - A 25-year-old chronically immunosuppressed woman with systemic lupus
      erythematosus (SLE) died after developing subacute granulomatous encephalitis
      caused by Acanthamoeba. Amoebic trophozoites were also found in the lung,
      suggesting a primary pulmonary focus of infection. The infectious encephalitis
      was difficult to differentiate from a flare-up of central nervous system lupus.
      This case illustrates that Acanthamoeba can cause fatal encephalitis in lupus
      patients, as well as in patients with acquired immunodeficiency syndrome as
      previously reported. To our knowledge, this is the first reported case of
      granulomatous amoebic encephalitis due to Acanthamoeba in a patient with SLE.

PMID- 9776116
TI  - Comparative study of tetranectin levels in serum and synovial fluid of patients
      with rheumatoid arthritis, seronegative spondylarthritis and osteoarthritis.
AB  - Tetranectin (TN) was assessed in paired synovial fluid (SF) and serum (S) samples
      from 27 patients with rheumatoid arthritis (RA), 23 with seronegative
      spondylarthritis (SSA) and 22 with osteoarthritis (OA). RA patients had a
      stronger correlation between serum and SF TN and a higher SF/S TN ratio than did
      SSA and OA patients. Moreover, the SF/S TN ratio exceeded 1 in most RA patients
      but not in SSA and OA patients, indicating the possibility of intra-articular TN
      synthesis in RA. A strong correlation of serum and SF TN with known inflammatory
      markers was observed in RA. The TN/proteinase inhibitors (PIs: alpha1
      antitrypsin, alpha2-macroglobulin) molar ratio in SF was lower in RA and SSA
      patients to a statistically significant degree than in OA patients. In RA, in
      contrast to SSA and OA, this ratio correlated positively with the SF interleukin
      8 (IL-8), responsible for neutrophil recruitment and degranulation, and
      negatively with erythrocyte sedimentation rate, serum C-reactive protein and
      fibrinogen, known markers of disease activity. In conclusion, patients with RA
      showed lower serum TN levels, a higher SF/S TN ratio and a lower SF TN/PI molar
      ratio than did SSA and OA patients, suggesting the implication of TN in the
      impaired regulation of fibrinolysis associated with the inflammatory process.

PMID- 9776119
TI  - Pyomyositis.
AB  - A case of non-tropical pyomyositis (PM), in a 63-year-old female patient,
      affecting gluteus and intrapelvic muscles is presented. Delayed diagnosis and
      treatment led to long-standing morbidity. Magnetic resonance imaging (MRI) of the
      pelvis provided valuable information on the nature and extent of the disease and
      helped to plan surgical management. MRI of the pelvis should be undertaken at an
      early-stage. Prompt examination of material obtained by aspiration or debridement
      would then permit an accurate diagnosis and appropriate management.

PMID- 9776120
TI  - Pancreatitis associated with pleural-mediastinal pseudocyst, panniculitis and
      polyarthritis.
AB  - We describe two patients with pancreatitis. One patient had acute pancreatitis of
      biliary origin and presented with small joint polyarthritis and panniculitis
      lesions. The other patient was originally hospitalised for dyspnoea with
      bilateral pleural effusion, and subsequently developed migratory polyarthritis.
      During his hospital stay he developed panniculitis lesions and a monoclonal IgG
      disorder of unknown significance. Very few patients with pancreatitis develop
      polyarthritis and panniculitis. The appearance of pseudocysts in the pleural and
      mediastinal cavity in the course of pancreatitis is an infrequent complication.

PMID- 9776122
TI  - Progressive pseudorheumatoid chondrodysplasia: a hereditary disorder simulating
      rheumatoid arthritis.
AB  - Progressive pseudorheumatoid chondrodysplasia is a rare hereditary disorder. This
      autosomal recessive condition is characterised by progressive arthropathy and
      platyspondyly. The symptoms are similar to those of rheumatoid arthritis but
      synovitis is absent. In this study a patient with inherited progressive
      pseudorheumatoid chondrodysplasia is presented.

PMID- 9776121
TI  - Septic arthritis caused by Haemophilus influenzae associated with endocarditis.
AB  - Septic arthritis with Haemophilus influenzae is infrequent in adults and often
      associated with an extra-articular septic focus. We report the case of a septic
      arthritis caused by H. influenzae in an elderly (89-year-old) female patient in
      whom an transoesophageal echocardiogram showed an aortic valve endocarditis.

PMID- 9776123
TI  - Factor XIII insufficiency in a patient with severe psoriasis vulgaris, arthritis,
      and infirmity.
AB  - Factor XIII (FXIII) links soluble fibrin monomers and collagen fibres to stable
      fibrin connections. Deficiency of FXIII, caused by dyspoiesis or increased
      consumption, results in a bleeding tendency and wound healing complications.
      Although the decrease of FXIII and successful replacement in patients with wound
      healing complications after surgery have been described by several authors, it is
      rarely considered that patients with autoimmune diseases, bleeding or healing
      complications may suffer from FXIII deficiency. We report a patient with severe
      psoriasis vulgaris generalisata with large, painful erythemas, bleeding tendency,
      joint contractions and infirmity, whose FXIII activity was 19%. After successful
      replacement the bleeding tendency vanished, and a marked improvement of skin and
      joint mobility allowed mobilisation and administration of physical therapy,
      whereby some independence and mobility were restored to the patient.

PMID- 9776125
TI  - Uncommon features of polyarteritis nodosa: psychosis and angio-oedema.
AB  - Psychosis and swelling of the face and hands are rarely observed in adult
      polyarteritis nodosa (PAN). We describe a 21-year-old woman who presented with
      fever, livedo reticularis, tender subcutaneous nodules and arthritis. These
      manifestations did not respond to prednisone, but remitted when the drug was
      tapered. She had had psychosis since the age of 16 years. During the flares of
      the disease she presented with facial, periorbital and hand swelling. This
      finding is rarely observed in adult PAN. Arteriography showed multiple small
      aneurysms, of the mesenteric vessels consistent with a diagnosis of PAN. Our
      report discusses the diagnosis of PAN and emphasises the uncommon presentation of
      this case.

PMID- 9776124
TI  - Successfully treated sulphasalazine-induced fulminant hepatic failure,
      thrombocytopenia and erythroid hypoplasia with intravenous immunoglobulin.
AB  - We report the simultaneous development of fulminant hepatic failure,
      thrombocytopenia and erythroid hypoplasia in a child treated with sulphasalazine.
      A 12-year-old girl with juvenile rheumatoid arthritis developed fulminant hepatic
      failure, thrombocytopenia and erythroid hypoplasia, which was confirmed by liver
      histology and bone marrow examination, 2 weeks after initiation of sulphasalazine
      therapy. The patient recovered after administration of high doses of intravenous
      immunoglobulin. This is the first reported case of the concurrent development of
      these complications associated with sulphasalazine hypersensitivity. The use of
      intravenous immunoglobulin may have helped in the treatment of this rare adverse
      effect of sulphasalazine.

PMID- 9776126
TI  - Unilateral sacroiliitis as an unusual complication of acupuncture.
AB  - Septic sacroiliitis is an uncommon disease and is rarely reported as a
      complication of acupuncture. We present a case of unilateral septic sarcoiliitis,
      which developed as a complication of acupuncture because of failure to sterilise
      the skin properly before treatment. Bone scan and computed tomography were
      positive for sacroiliitis. After a course of antibiotics with oxacillin for 6
      weeks, the condition was completely improved. This case report stresses the
      importance of sterilisation procedures before acupuncture therapy.

PMID- 9776127
TI  - Neurotoxic effects of +/-fenfluramine and phenteramine, alone and in combination,
      on monoamine neurons in the mouse brain.
AB  - Until recently, (+/-)fenfluramine (FEN) was widely prescribed as an appetite
      suppressant. In animals, FEN is a potent and selective brain serotonin
      neurotoxin. The present studies assessed the effects of phentermine (PHEN), an
      appetite suppressant frequently used clinically in combination with FEN, on FEN
      induced serotonin neurotoxicity. Groups (n = 6/group) of mice were treated with
      FEN (10 mg/kg), PHEN (20 mg/kg or 40 mg/kg), FEN (10 mg/kg) plus PHEN (20 mg/kg
      or 40 mg/kg), or vehicle twice daily for four days. Food intake and body weight
      were measured during and after drug treatment. Brains were evaluated for regional
      brain serotonin and dopamine axonal markers two weeks after drug treatment. PHEN
      enhanced the anorectic and weight-reducing effects of FEN. PHEN also
      significantly enhanced FEN's long-term toxic effects on 5-HT axons. This effect
      was evident in some (hypothalamus, striatum) but not all (hippocampus, cortex)
      brain regions examined. PHEN alone produced no long-term effects on 5-HT axonal
      markers. However, whether given alone or in combination with FEN, PHEN produced
      significant, dose-related decreases in striatal DA axonal markers. These results,
      coupled with those from previous studies, suggest that PHEN has the potential to
      exacerbate FEN-induced serotonin neurotoxicity, if utilized in certain doses.
      Further, the present results indicate that PHEN possesses dopamine (DA)
      neurotoxic potential. The relevance of these data to humans previously treated
      with FEN/PHEN is discussed.

PMID- 9776128
TI  - Electrically evoked [3H]GABA release from cerebral cortical cultures: an in vitro
      approach for studying glutamate-induced neurotoxicity.
AB  - In the present study the [3H]GABA release in the rat cerebral cortex primary
      cultures, kept at rest or electrically stimulated, was measured. In addition, the
      development of excitotoxic cell damage caused by pretreating the cells for 10 min
      with increasing glutamate concentrations (10-300 microM) was examined 2 and 24 h
      after the insult. Cellular injury was quantitatively assessed by measuring the
      electrically-evoked [3H] GABA release, the [3H] GABA uptake, and 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide staining. Trains of
      electrical pulses at different frequencies (2, 5, 10, and 20 Hz) applied to the
      cultures elicited a [3H]GABA release which was frequency related, Ca++-dependent,
      and tetrodotoxin sensitive. Either 2 or 24 h after glutamate exposure, the
      electrically evoked [3H]GABA release was reduced by glutamate in a concentration
      dependent manner, while [3H]GABA uptake and 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide staining appeared less sensitive. The N-methyl-D
      aspartate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and
      metabotropic receptor antagonists were tested on 100 microM glutamate-exposed
      cells and a prominent N-methyl-D-aspartate receptor-mediated component was
      observed. The present findings indicate that the electrically-evoked [3H]GABA
      release from cerebral cortical cells could represent a useful approach not only
      to study the spike-triggered neurosecretion but also to the neuronal damage
      caused by glutamate, as well as to test potential neuroprotective compounds.

PMID- 9776129
TI  - Increased responsiveness of mesolimbic and mesostriatal dopamine neurons to
      cocaine following repeated administration of a selective kappa-opioid receptor
      agonist.
AB  - Previous data have shown that the repeated administration of kappa-opioid
      receptor agonists attenuates the acute behavioral effects of cocaine. The site
      and mechanism by which kappa-agonists interact with this psychostimulant,
      however, are unknown. Accordingly, the present microdialysis study characterized
      the effects of prior, repeated administration of the selective kappa-opioid
      receptor agonist U69593 on basal and cocaine-evoked DA levels within the nucleus
      accumbens (NAC) and caudate putamen (CPU). The influence of U69593 treatment on
      the locomotor-activating effects of an acute cocaine challenge was also assessed.
      Rats received once daily injections of U69593 (0.16-0.32 mg/kg/day) or vehicle
      (1.0 ml/kg/day) for 3 days. The behavioral and neurochemical effects produced by
      an acute cocaine challenge (20 mg/kg i.p.) were assessed 2 days following
      treatment cessation. Administration of cocaine to control animals increased
      locomotor activity. This effect was attenuated in animals which had previously
      received U69593 (0.32 mg/kg/day x 3 days). Prior administration of U69593 failed
      to modify basal DA levels in either the NAC or CPU. Thus, 2 days following the
      cessation of U69593 treatment, dialysate DA levels did not differ from that of
      controls. Administration of cocaine to vehicle-treated animals increased
      dialysate levels of DA in both brain regions. However, in animals previously
      exposed to U69593 (0.32 mg/kg/day x 3 days), a significant enhancement in the
      response of DA neurons to cocaine was seen. These data demonstrate that prior,
      repeated administration of a selective kappa-opioid receptor agonist attenuates
      the locomotor-activating effects of cocaine and increases cocaine-evoked DA
      overflow in terminal projection areas of mesostriatal and mesolimbic DA neurons.
      These findings indicate that the behavioral interactions of kappa-agonists with
      cocaine observed in this and previous studies cannot be attributed to a
      presynaptic inhibition of DA release. Rather, they suggest that postsynaptic or
      non-DA mechanisms mediate the interaction of these agents with cocaine.

PMID- 9776130
TI  - [18F]fluoroethoxy-benzovesamicol, a PET radiotracer for the vesicular
      acetylcholine transporter and cholinergic synapses.
AB  - Loss of cholinergic transmission in the cortex and hippocampus is a
      characteristic feature of Alzheimer's disease, and visualization of functional
      cholinergic synapses in the brain with PET could be a useful method for studying
      this degenerative condition in living humans. We investigated
      [18F]fluoroethoxybenzovesamicol, (-)-[18F] FEOBV,(-)-(2R,3R)-trans-2-hydroxy-3-(4
      phenylpiperidino)-5-(2-[18F ]fluoroethoxy)-1,2,3,4-tetralin, a high affinity
      positron emitting ligand for the vesicular acetylcholine transporter, as a
      potential in vivo cholinergic synapse mapping agent. Rodent biodistribution,
      dosimetry, stereospecificity of biological effects, pharmacologic blocking
      studies, in vivo rodent brain autoradiography and metabolites were examined. (-)
      [18F]FEOBV brain uptake following intravenous injection was robust, with 2.65%
      dose/brain in mice at 5 min, and the regional localization matched the known
      distributions of presynaptic cholinergic markers at later times. Both the
      cholinergic localization and curare-like effects of FEOBV were associated with
      the "(-)"-enantiomer exclusively. (-)-[18F]FEOBV regional brain distribution in
      rodents was changed little by pretreatment with haloperidol, (+)-3-PPP, or E
      2020, indicating FEOBV, unlike other vesamicol analogs, did not interact in vivo
      with dopamine or sigma receptor systems. Autoradiography of rat brain 3 h
      following i.v. injection of (-)-[18F]FEOBV showed high localization in brain
      areas rich in presynaptic cholinergic elements. Metabolic defluorination in
      rodents was modest, and analysis of brain tissue following tracer administration
      found FEOBV as the only extractable radioactive species. (-)-[18F]FEOBV dosimetry
      calculated from rat data estimate 10 mCi doses can be given to humans. These
      studies show FEOBV maps cholinergic areas with high specificity in vivo, and may
      provide a noninvasive means to safely and accurately gauge the functional
      integrity of cholinergic synapses in man using PET.

PMID- 9776131
TI  - Repeated treatment with the selective kappa opioid agonist U-69593 produces a
      marked depletion of dopamine D2 receptors.
AB  - U-69593, the selective K-opioid agonist, was repeatedly administered in single
      daily injections (0.32 mg/kg) to male, Sprague-Dawley rats. Two or ten days
      later, the rats were euthanized and dopamine D1 and D2 receptors were measured
      using (3H]SCH 23390 or [3H]sulpiride, respectively, in caudate putamen and
      nucleus accumbens. Two days after the last of three injections, dopamine D2
      receptors in the caudate putamen were decreased by approximately 40%, with no
      change in D1 receptors. Dopamine D2 receptor number had returned to normal by 10
      days posttreatment. In contrast, in the nucleus accumbens there was a small,
      nonsignificant decrease in dopamine D2 receptors 2 days after treatment, but a
      large increase (65%) after 10 days. In agreement with the changes in D2
      receptors, there was a significant downward shift in the locomotor activity curve
      for the D2 agonist quinpirole after a 2-day withdrawal. There were no differences
      in either the total amount of dopamine taken up or in the IC50 for cocaine to
      inhibit dopamine uptake following this treatment, suggesting that the dopamine
      transporter and presynaptic terminals were intact. The results of these studies
      demonstrate that repeated administration of a selective K-opioid agonist induces
      long-term alterations in dopamine D2 receptors. Furthermore, the finding that
      these changes in receptor number require both repeated injections and a
      withdrawal time greater than 1 day suggests that these alterations are
      compensatory in nature.

PMID- 9776132
TI  - Chemical phenotype of calretinin interneurons in the human striatum.
AB  - We recently reported the existence of a new class of aspiny interneurons
      characterized by their immunoreactivity for the calcium-binding protein
      calretinin (CR) in human striatum. This group is composed of numerous medium
      sized (10-20 microm) neurons with poorly branched dendrites and a smaller number
      of large-sized (24-42 microm) neurons with highly ramified dendrites. We further
      demonstrated the selective sparing of the medium-sized, but not all the large
      sized, CR+ striatal neurons in Huntington's disease. In the present study, we
      applied a double-antigen localization method to postmortem striatal tissue
      obtained from normal individuals to further characterize the chemical phenotype
      of these two subsets of CR+ neurons. Our results reveal that in the medium-sized
      neurons, CR is not colocalized with any of the following current markers of
      striatal neurons: calbindin, parvalbumin, beta-nicotinamide adenine dinucleotide
      phosphate-diaphorase (NADPH-d), or choline acetyltransferase (ChAT). Furthermore,
      quantitative estimates show that the medium-sized CR+ neurons are by far the most
      abundant type of interneurons in the human striatum. In contrast, CR is
      colocalized with ChAT in about 80% of the large-sized CR+ neurons. Thus, the
      medium-sized CR+ neurons appear to form a distinct class of striatal
      interneurons, whereas most of the large-sized CR+ neurons belong to the
      population of giant cholinergic neurons. This study has provided the first
      exhaustive characterization of the chemical phenotype of the CR + neurons in the
      human striatum.

PMID- 9776133
TI  - Time-course of the cannabinoid receptor down-regulation in the adult rat brain
      caused by repeated exposure to delta9-tetrahydrocannabinol.
AB  - Recent studies have demonstrated that the pharmacological tolerance observed
      after prolonged exposure to plant or synthetic cannabinoids in adult individuals
      seems to have a pharmacodynamic rather than pharmacokinetic basis, because down
      regulation of cannabinoid receptors was assessed in the brain of cannabinoid
      tolerant rats. In the present study, we have examined the time-course of
      cannabinoid receptor down-regulation by analyzing cannabinoid receptor binding,
      using autoradiography, and mRNA expression, using in situ hybridization, in
      several brain structures of male adult rats daily exposed to delta9
      tetrahydrocannabinol (delta9-THC) for 1, 3, 7, or 14 days. With only the
      exception of a few number of areas, most of the brain regions exhibited a
      progressive decrease in cannabinoid receptor binding. Two facts deserve to be
      mentioned. First, the pattern of this down-regulation process presented
      significant regional differences in terms of onset of the decrease and magnitude
      reached. Second, the loss of cannabinoid receptor binding was usually accompanied
      by no changes in its mRNA expression. Thus, some structures, such as most of the
      subfields of the Ammon's horn and the dentate gyrus in the hippocampus, exhibited
      a rapid (it appeared after the first injection) and marked (it reached
      approximately 30% of decrease after 14 days) reduction of cannabinoid receptor
      binding as a consequence of the daily delta9-THC administration. However, no
      changes occurred in mRNA levels. Decreased binding was also found in most of the
      basal ganglia, but the onset of this reduction was slow in the lateral caudate
      putamen and the substantia nigra (it needed at least three days of daily delta9
      THC administration), and, in particular, in the globus pallidus (more than 3
      days). The magnitude of the decrease in binding was also more moderate, with
      maximal reductions always less than 28%. No changes were seen in the
      entopeduncular nucleus and only a trend in the medial caudate-putamen. However,
      the decrease in binding in some basal ganglia was, in this case, accompanied by a
      decrease in mRNA levels in the lateral caudate-putamen, but this appeared after 7
      days of daily delta9-THC administration and, hence, after the onset of binding
      decrease. In the limbic structures, cannabinoid receptor binding decreased in the
      septum nuclei (it needed at least 3 days of daily delta9-THC administration),
      tended to diminish in the nucleus accumbens and was unaltered in the basolateral
      amygdaloid nucleus, with no changes in mRNA levels in these last two regions.
      Binding also decreased in the superficial and deep layers of the cerebral cortex,
      but only accompanied by trends in mRNA expression. The decrease in binding was
      initiated promptly in the deep layer (after the first injection) and it reached
      more than 30% of reduction after 14 days of daily delta9-THC administration,
      whereas, in the superficial layer, it needed more than 3 days of daily delta9-THC
      administration and reached less than 30% of reduction. Finally, no changes in
      binding and mRNA levels were found in the ventromedial hypothalamic nucleus. In
      summary, the daily administration of delta9-THC resulted in a progressive
      decrease in cannabinoid receptor binding in most of the brain areas studied, and
      it was a fact that always occurred before the changes in mRNA expression in those
      areas where these existed. The onset of the decrease in binding exhibited
      regional differences with areas, such as most of the hippocampal structures and
      the deep layer of the cerebral cortex, where the decrease occurred after the
      first administration. Other structures, however, needed at least 3 days or more
      to initiate receptor binding decrease. Two structures, the entopeduncular nucleus
      and the ventromedial hypothalamic nucleus, were unresponsive to chronic delta9
      THC administration, whereas others, the medial caudate-putamen and the
      basolateral amygdaloid nucleus, only exhibited trends.

PMID- 9776134
TI  - The antiparkinsonian drug budipine stimulates the activity of aromatic L-amino
      acid decarboxylase and enhances L-DOPA-induced dopamine release in rat substantia
      nigra.
AB  - The present study examined the effects of the antiparkinsonian drug budipine on
      dopamine synthesis and release from L-DOPA in the substantia nigra of reserpine
      treated rats. Budipine (at 100 microM, but not 10 microM) applied by reverse
      dialysis to the nigra caused a small and significant rise in dopamine recovery in
      normal rats, but not in rats pretreated with reserpine (4 mg/kg i.p. for 18
      hours) and alpha-methyl-p-tyrosine (alpha-MPT; 200 mg/kg i.p. for 1 hour to limit
      dopamine synthesis to L-DOPA). L-DOPA applied to the nigra by reverse dialysis in
      reserpine + alpha-MPT-treated rats, increased the recovery of dopamine when
      applied at 5 or 10 microM, but not at 2 microM. Coadministration of budipine (10
      microM) significantly enhanced L-DOPA-induced dopamine (and DOPAC) release with 5
      microM L-DOPA, but not with 2 or 10 microM L-DOPA. This potentiation was even
      more pronounced when the budipine concentration was raised to 100 microM
      (equivalent to approximately 10 microM extracellularly). Pretreating rats with
      budipine (5, 12.5, or 20 mg/kg i.p.) for 1 hour significantly raised the activity
      of the enzyme L-aromatic amino acid decarboxylase in the striata and nigras of
      intact rats, as well as in rats pretreated with reserpine alone (5 mg/kg i.p.),
      without altering tissue levels of dopamine or its metabolites. It is suggested
      that the beneficial effects of budipine, when used as an adjunct to L-DOPA
      therapy of Parkinson's disease, may be due to an increase in the bioconversion of
      L-DOPA with a consequent rise in synaptic dopamine. These actions of budipine may
      be related to its weak NMDA receptor antagonist property.

PMID- 9776135
TI  - Cellular electrophysiological effects of chronic fluoxetine and duloxetine
      administration on serotonergic responses in the aging hippocampus.
AB  - The pharmacological and physiological effects of chronic administration of the
      selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitor (SSRI)
      fluoxetine and the dual 5-HT/norepinephrine (NE) reuptake inhibitor duloxetine
      were compared on 5-HT-mediated electrophysiological responses recorded in the
      hippocampus of young (3-5 months) and old (17-20 months) female Fischer 344 rats.
      Fluoxetine, duloxetine, or vehicle (saline) was administered once daily for 14
      days (10 mg/kg, i.p.) and extracellular recordings of spontaneously firing CA1
      and CA3 pyramidal neurons were conducted 24 h following the last injection using
      microiontophoretic drug application techniques in a chloral hydrate anesthetized
      preparation. The recovery times (RT50 values; sec) following 5-HT application on
      pyramidal neurons were significantly increased in the young and old chronic
      fluoxetine (FLX) treated groups (73% and 104%, respectively; P < 0.05), but not
      chronic duloxetine- (DLX) or vehicle- (VEH) treated groups. Following prolonged
      application of duloxetine (5-10 min), the 5-HT RT50 values were significantly
      increased in the young FLX groups as compared to the age-matched DLX- and VEH
      treated groups. In contrast, a significant decline in the time to recovery
      produced by 5-HT (52%) was observed in the old vs. young FLX-treated group
      following the second co-application of 5-HT with duloxetine. Within each drug
      treatment and age group, co-application of duloxetine and 5-HT did not alter the
      inhibitory responses (IT50 values; nC) produced by the application of 5-HT alone.
      These results demonstrate cellular adaptive changes in serotonergic neuronal
      function occur following repeated exposure to 5-HT reuptake inhibitors in an age
      dependent manner.

PMID- 9776136
TI  - Characterizing cortical neuron injury with Fluoro-Jade labeling after a
      neurotoxic regimen of methamphetamine.
AB  - We used Fluoro-Jade, a recently-developed fluorescent indicator of neuronal
      damage, to identify neurons injured 1-21 days after repeated injections of
      methamphetamine (m-AMPH) or saline. The m-AMPH-treated rats showed Fluoro-Jade
      positive neurons in parietal cortex (layers III and IV) and had less striatal
      tyrosine hydroxylase immunoreactivity than did saline-injected controls. Fluoro
      Jade positive neurons were greatest in number 3 days post-treatment; some
      fluorescent neurons displayed bud-like surface protrusions. These observations
      support the hypothesis that certain neocortical neurons degenerate after m-AMPH.

PMID- 9776138
TI  - Opposing effects of clomipramine on [125I]RTI-55 and [3H]N-methylspiperone
      binding in mouse striatum: important role of other factors than endogenous
      dopamine?

PMID- 9776137
TI  - Selective regulation of dopamine transporter binding in the shell of the nucleus
      accumbens by adrenalectomy and corticosterone-replacement.

PMID- 9776139
TI  - Cell-mediated immune responses and cytotoxicity to mycobacterial antigens in
      patients with tuberculous pleurisy in Brazil.
AB  - Evaluating human immune response to defined Mycobacterium tuberculosis antigens
      in patients with different clinical forms of tuberculosis may help in elucidating
      pathogenesis and in vaccine development. In the present report we evaluated the
      lymphocyte proliferation, cytokine production and natural killer cell
      cytotoxicity as parameters to screen four mycobacterial recombinant antigens.
      Pleural fluid mononuclear cells (PFMC) and peripheral blood mononuclear cells
      (PBMC) from 13 HIV-negative patients with tuberculous pleurisy, living in a
      tropical region of Brazil were used in these assays. Crude M. tuberculosis
      antigen and recombinant 70-, 65- and 38-kDa mycobacterial antigens, induced
      greater proliferation in PFMC than in PBMC. IFN-gamma, TNF-alpha, IL-4 and IL-10
      were evaluated in the PFMC supernatants stimulated by these antigens. Both crude
      and 70-kDa antigens induced higher levels of IFN-gamma, TNF-alpha and IL-10.
      There was a significant positive correlation between IFN-gamma and the
      proliferative response induced by crude M. tuberculosis antigen, and an inverse
      correlation was identified between IL-10 and cell proliferation. IL-4 was not
      detected in the supernatants of pleural fluid mononuclear cell cultures
      stimulated by either crude, or recombinant antigens. TNF-alpha was detected in
      variable amounts in supernatants of PFMC stimulated by all antigens tested.
      Natural killer cytotoxicity was induced by both crude and 70-kDa antigen. Our
      results demonstrate that cells present at the site of disease recognized three of
      the antigens screened, as shown by lymphocyte proliferation and production of
      regulatory and inflammatory cytokines, and the results obtained with PFMC were
      consistently higher than those obtained with homologous PBMC.

PMID- 9776140
TI  - A cDNA encoding a pepsinogen-like, aspartic protease from the human roundworm
      parasite Strongyloides stercoralis.
AB  - Using degenerate oligonucleotide primers based on conserved active site residues,
      we have isolated a cDNA encoding an aspartic protease from the nematode parasite
      Strongyloides stercoralis, an important, enteric pathogen of humans. cDNAs
      encoding the aspartic protease were isolated from the infective, third stage
      larvae of the parasite as well as from free-living, rhabditiform larvae. Based on
      comparisons of other aspartic proteases, the cDNA encoded a short signal peptide,
      an enzyme pro-segment of 35 amino acid residues, and mature enzyme of 337
      residues. Homology alignments using the proenzyme sequence showed that the novel
      S. stercoralis zymogen was 36% identical to human pepsinogen A and 36% identical
      to pepsinogen C (progastricin) from humans and macaques. Phylogenetic analyses
      using the Phylip program and analysis of Glx/Asx and Leu/Ile ratios indicated
      that the proenzyme was closely related to pepsinogen A-like enzymes from the free
      living nematode Caenorhabditis elegans and Haemonchous contortus, a nematode
      parasite of the gastro-intestinal tract of sheep. We have termed this novel
      enzyme strongyloidespepsin.

PMID- 9776142
TI  - Detection of a chemotactic factor for neutrophils in extracts of female
      Onchocerca volvulus.
AB  - Neutrophilic granulocytes and macrophages are the dominant inflammatory cell
      types observed in the vicinity of and attached to adult Onchocerca volvulus in
      the subcutaneous nodules. Crude extract from female O. volvulus was examined for
      chemotactic activity for peripheral neutrophils from healthy individuals by use
      of an endogenous component chemotactic assay in Boyden chambers. Significant
      chemotactic responses of neutrophils were detected using O. volvulus extracts at
      > or = 15 microg/ml in a dose-dependent manner. Checkerboard analysis
      demonstrated low chemokinetic in addition to chemotactic activity. Neutrophil
      migration was also elicited by excretory-secretory products of vital females.
      Fractionation of the female worm extract by FPLC revealed two components with
      chemotactic activity, one with a molecular mass less than 12 kDa and another with
      a molecular mass of > 200 kDa. Immunohistological examination of onchocercomas
      containing only one adult alive filarial worm demonstrated that neutrophils were
      accumulated near and attached to the cuticle of immature females, females
      producing microfilariae and males.

PMID- 9776141
TI  - Efficacy of albendazole against Giardia and hookworm in a remote Aboriginal
      community in the north of Western Australia.
AB  - The parasitological, clinical efficacy and tolerability of albendazole in the
      treatment for both giardiasis and hookworm infection in a remote Aboriginal
      population was investigated. Albendazole at a dose rate of 400 mg daily for 5
      days was highly effective in reducing hookworm egg numbers and both Giardia
      antigen and cysts. The 36.6% prevalence of Giardia prior to treatment fell to 12%
      between days 6 and 9, 15% for days 10-17 and rose to 28% between days 18 and 30.
      Tolerability and clinical efficacy were excellent. The effect of albendazole on
      hookworm was longer lasting than that on Giardia, reducing percent infection from
      over 76-2% on days 6-9 and zero by day 18-30 despite conditions highly conducive
      to rapid re-infection. We conclude that albendazole is highly efficacious against
      both parasites when used as described but that long term community benefit may
      require additional education programmes to avoid re-infection with Giardia
      although treatment strategies would seem appropriate for hookworm.

PMID- 9776143
TI  - Trypanosome infections and tick infestations: susceptibility in N'Dama, Gobra
      zebu and Gobra x N'Dama crossbred cattle exposed to natural challenge and
      maintained under high and low surveillance of trypanosome infections.
AB  - Susceptibility to trypanosome infections and tick infestations was assessed in 51
      N'Dama, 48 Gobra zebu and 37 Gobra x N'Dama crossbred (F1) cattle exposed to
      field-tick infestations and natural high tsetse challenge over more than one
      year. From these cattle, 12 animals of each breed were randomly selected and
      examined parasitologically for trypanosome infections and packed cell volume
      (PCV) twice a week (high surveillance, group HS). In the remaining 100 cattle
      trypanosome infection and PCV were monitored monthly (low surveillance, group
      LS). Mortality rates were recorded in both groups. Tick infestation was
      quantified fortnightly from all animals in group HS and from four to seven
      randomly selected animals of each breed in group LS. In both HS and LS groups,
      trypanocidal drug treatment was administered to trypanosome positive animals with
      PCV equal to or less than 20% or when they showed clinical evidence (dullness,
      weight loss) of trypanosomosis. In both groups, N'Dama cattle exhibited a
      superior capacity to control trypanosome infections and limit tick burdens.
      Particularly, in group HS N'Dama cattle showed lower trypanosome infection rate,
      higher mean PCV value, lower requirement for trypanocide treatments and lower
      tick load than crossbred and Gobra cattle in the corresponding group (P < 0.05 or
      greater). This was also true in N'Damas in comparison with crossbreds in group
      LS. Unfortunately, the high mortality occurring in Gobra cattle in group LS did
      not allow within group comparative analysis between N'Dama, Gobra and crossbred
      cattle overall the study period. No death occurred in N'Dama cattle maintained
      under high surveillance of trypanosome infection, while approximately 8% of
      crossbreds and 50% of Gobras died of trypanosomosis. In group LS, all Gobra and
      more than 70% of crossbred cattle died. In this group, mortality in N'Dama was
      limited to less than 16%. In both groups, differences in mortality were
      significantly higher (P < 0.01) in Gobras than in N'Damas. Within breed, animals
      of the three breeds maintained under high surveillance of trypanosomal infection
      showed higher mean PCV values, lower tick burdens and required proportionally
      less trypanocide treatments than corresponding cattle in group LS. The infection
      rate in N'Dama under high surveillance was lower in comparison with N'Dama cattle
      in group LS. There was no significant difference in mortality between groups
      within the N'Dama breed. Conversely, mortality rates were lower in crossbred and
      Gobra in group HS than in respective cattle in group LS. It was concluded that
      cattle of the three breeds suffered from trypanosomosis and that trypanosome
      infections affected tick susceptibility. However, N'Dama showed a superior
      ability to limit both the pathological effects of trypanosomosis and the level of
      tick infestations. Therefore, considering the cost of labour and consumable
      equipment required for a high surveillance, use of multi-disease resistant N'Dama
      cattle is recommended for the low-input traditional African farming systems in
      areas where trypanosomosis, ticks and tick-borne diseases are constraints to
      livestock production. Additional comparative investigations are needed to assess
      the impact of high surveillance scheme of trypanosome infection in different
      production systems in trypanotolerant and trypanosusceptible cattle exposed to
      different gradients of tsetse challenge.

PMID- 9776145
TI  - Measurement of public health importance of schistosomiasis: problems and
      prospects.

PMID- 9776144
TI  - Some gastro-intestinal parasites of zoonotic (public health) importance commonly
      observed in old world non-human primates in Kenya.
AB  - A study was undertaken to categorise some gastro-intestinal (GIT) parasites
      commonly observed in Kenyan non-human primates (NHPs) on the basis of their
      health implications for humans. Six species of locally available non-human
      primates, namely olive baboons (Papio cyanocephalus anubis), Vervet monkey
      (Cercopithecus aethiops), Sykes monkey (Cercopithecus mitis), Black and white
      colobus (Colobus abyssinicus), Debrazzas monkey (Cercopithecus neglectus) and
      Grey and Black mangabeys (Cercocebus torquatus and Cercocebus albigena) which
      were imported from Zaire (Democratic Republic of Congo) were sampled. Simple
      laboratory methods involving microscopic examination of stained faecal smears
      were used. Wet faecal smears stained with iodine and unstained controls were used
      for conventional parasites while acid fast staining was employed to detect
      Cryptosporidium oocysts. Both helminths and protozoan parasites were detected in
      varying rates in all primate species. Trichuris sp. was the most frequent
      helminth followed by Strongyloides fulleborni, Strongyles sp. and Schistosoma
      mansoni in that order. Entamoeba coli was the most common protozoan followed,
      respectively, by Balantidiun coli and Entamoeba histolytica. All primate species
      examined were infected with all the parasites listed except the black and white
      colobus. Cryptosporidium was found in both clinically normal and diarrhoeic
      baboons and vervets. Most taxa of parasites observed could prejudice human
      welfare directly through infection and causation of illness and indirectly
      through increased cost of livestock production and decreased availability of
      animal proteins. The potential of some of the agents to cause opportunistic
      infections in immuno-compromised persons was suggested as a likely threat to
      man's well-being. This would warrant such person's exemption from high risk
      operations at primate and other animal facilities in developing countries.
      Further, specific studies are needed to provide data on the epidemiology, socio
      economic impact and pathogenicity of the primate parasites to other species of
      animals and man.

PMID- 9776146
TI  - Surgical Internet at a glance: volume V.

PMID- 9776147
TI  - Determining the real bottom line and true cost of surgical practice using
      relative value units.

PMID- 9776148
TI  - Vena cava occlusion with balloon to control blood pressure during deployment of
      transluminally placed endovascular graft.
AB  - Transluminally placed endovascular graft (TPEG) replacement has been applied to
      treat various aortic diseases. At the moment of deployment, TPEG receives a
      pressure pulse force to shove it distally, which possibly results in
      misplacement. Moreover, deploying the TPEG in the aorta increases cardiac
      afterload, which may damage myocardial function. To avoid these risks, we
      developed a new technique to control blood pressure by almost complete venous
      return occlusion. Two occlusion balloon catheters are inserted into the superior
      and inferior vena cava via the femoral vein. TPEG is deployed at the proper
      position during inflation of the vena cava balloon to maintain a blood pressure
      as low as 60 mm Hg by cardiac preload blockage. We, thus far, have not
      experienced even a trivial sequela with this technique.

PMID- 9776149
TI  - Early experience of endoscopic extirpation of benign breast tumors via an extra
      mammary incision.
AB  - The early results of 6 patients with a benign breast mass who underwent an
      endoscopic extirpation via an extra-mammary incision were presented. Under
      general anesthesia in either a lateral or supine position, a 12-mm and two 5-mm
      incisions in the infra-mammary line in 2 patients and in the mid-axillary line in
      the remaining 4 patients were made. The tumors were then endoscopically
      extirpated. Preoperative aspiration needle cytology revealed six fibroadenomas in
      5 patients and one intraductal papilloma in the other patient. All patients were
      single females with a mean age of 22.5 years. The maximal size of the masses was
      5 cm on average. The average operation time was 3 hours 20 minutes. Regarding
      postoperative complications, subcutaneous emphysema extending to the neck due to
      CO2 gas inflation and a burn in the skin were seen in 1 patient each; however, no
      further treatment was required in these cases. The postoperative hospital stay
      was 1.7 days on average, and all patients were extremely satisfied with the
      cosmetic results of the procedure. The cosmetic results are drastically improved
      by the application of endoscopic removal via extra-mammary approaches, which are
      newly introduced, for benign breast tumors.

PMID- 9776150
TI  - Prospective, randomized, double-blind study of prophylactic antibiotics in
      axillary lymph node dissection.
AB  - BACKGROUND: Antibiotic prophylaxis is controversial in patients undergoing
      axillary lymph node dissection (ALND). We determined whether preoperative
      antibiotics decreased incidence or treatment cost of infectious complications
      following ALND. METHODS: Two hundred patients entered this prospective,
      randomized, double-blind trial. Patients received either placebo or cefonicid
      preoperatively. Loco-regional signs of infection were monitored for 4 weeks
      postoperatively. RESULTS: There was a trend toward fewer infections in the
      prophylactic group (placebo 13% versus cefonicid 6%; P = 0.080). Cefonicid
      significantly decreased severe infections requiring hospitalization (placebo 8%
      versus cefonicid 1%; P = 0.033). Cefonicid also decreased the treatment cost of
      infection per patient ($49.80 versus $364.87). CONCLUSIONS: We demonstrated a
      trend toward fewer overall infections and significantly fewer severe infections
      in patients given prophylactic antibiotics, which translated into a decrease in
      the cost of treatment for infectious complications. These findings support
      antibiotic prophylaxis for patients undergoing ALND.

PMID- 9776152
TI  - Surgical considerations in the contemporary management of biliary tract disease
      in the postpartum period.
AB  - BACKGROUND: Excluding sterilization procedures, no experience with laparoscopic
      procedures in the postpartum period has been reported. The postpartum patient may
      have unique characteristics that must be recognized for safe management. METHODS:
      The authors prospectively studied 1,100 consecutive biliary patients in a private
      surgical practice since the introduction of laparoscopic cholecystectomy (LC).
      The group includes 34 patients who presented with biliary tract disease and were
      operated upon within 6 weeks of obstetrical delivery. Laparoscopic procedures
      were performed on these 34 patients 1 to 42 days following vaginal (26) or
      Cesarean (8) deliveries. RESULTS: All patients had calculous cholecystitis.
      Choledocholithiasis was documented in 10 (29%) patients, including 3 patients
      (9%) with missed common duct stones, and strongly suggested in 5 (15%) others.
      Open biliary procedures were required for 2 patients. One patient returned to
      surgery for an ERCP-related complication. Follow up is known for all patients.
      There were no delayed complications. CONCLUSIONS: The laparoscopic approach to
      biliary tract disease in the postpartum period is safe. Recent vertical Cesarean
      incisions can withstand the strain of a reduced pneumoperitoneum. The high
      incidence of choledocholithiasis calls for routine cholangiography in the
      postpartum patient.

PMID- 9776151
TI  - Characteristics of women surgeons in the United States.
AB  - BACKGROUND: Women surgeons are becoming increasingly prevalent. Despite this,
      there have been few studies of personal or professional characteristics of US
      surgeons of either gender. METHODS: Data were taken from the Women Physicians'
      Health Study, a nationally representative random sample (n = 4,501 respondents)
      of US women physicians, and data were analyzed in SUDAAN. RESULTS: Surgeons were
      younger, and more likely to be US born, white, unmarried, and childless than were
      other women physicians; their personal health behaviors were similar to those of
      others. They worked significantly more clinical hours and call nights, but were
      not more likely to report feeling that they worked too much, had too much work
      stress, or had less control of their work environment. Their career satisfaction
      was similar to that of other women physicians, and satisfaction with their
      specialty was greater. They were less avid preventionists than were primary care
      practitioners, and somewhat less avid than other specialists. CONCLUSIONS: Women
      surgeons differ in interesting and important ways from other women physicians.

PMID- 9776153
TI  - A randomized controlled trial of extraperitoneal bupivacaine analgesia in
      laparoscopic hernia repair.
AB  - BACKGROUND: The limited space developed in totally extraperitoneal laparoscopic
      inguinal hernia repair (TEP) provides the ideal setting for direct instillation
      of local anesthetic. This study evaluates the efficacy of extraperitoneal
      bupivacaine analgesia in patients undergoing day-care TEP. METHODS: Fifty-six
      consecutive patients were randomized to intraoperative extraperitoneal
      instillation of bupivacaine (n = 29) or normal saline control (n = 27). Patients
      were blindly assessed on discharge from hospital, at 24 hours, 1 week, and 1
      month postoperatively. RESULTS: Compared with controls, patients treated with
      bupivacaine had lower median (range) visual analogue pain scores on discharge
      (1.5 [0 to 5.9] versus 3.7 [0.2 to 6.9], P = 0.03), and were more frequently pain
      free (54% versus 31%, P = 0.078). Although this difference had gone by 24 hours,
      the bupivacaine group continued to recover faster; stopping analgesia earlier (2
      [0 to 7] days versus 3 [0 to 21] days, P = 0.01) and returning to full activity
      earlier (2.5 [1 to 14] days versus 5 [1 to 21] days, P = 0.013). Of bupivacaine
      patients 100% were completely satisfied with the procedure compared with 81% of
      controls (P = 0.02). CONCLUSION: Extraperitoneal bupivacaine minimizes pain
      following day-care TEP repair, facilitates recovery, and increases patient
      satisfaction. Benefits persist beyond the pharmacological action of bupivacaine.

PMID- 9776154
TI  - A prospective randomized trial of intraoperative bupivacaine irrigation for
      management of shoulder-tip pain following laparoscopy.
AB  - BACKGROUND: Postoperative shoulder-tip pain (STP) frequently occurs following
      laparoscopic surgery. In an attempt to abrogate this complication we
      prospectively evaluated the efficacy of intraoperative irrigation of the
      diaphragm with bupivacaine. METHODS: One hundred and five consecutive patients
      undergoing laparoscopic surgery were prospectively randomized to treatment or
      control groups. Treatment group (B, n = 55) received irrigation with 10 mL 0.5%
      bupivacaine in 500 mL saline and control group (A, n = 50) received an equal
      volume of normal saline. Each dome of the diaphragm was irrigated with 250 mL of
      either solution at the end of surgery. Laparoscopic procedures performed included
      cholecystectomy (n = 63), Nissen fundoplication (n = 21), appendicectomy (n = 7),
      hernia repair (n = 4), and diagnostic laparoscopy (n = 10). Patients' anesthesia
      and perioperative analgesia were standardized. STP was recorded on a visual
      analogue pain scale (VAPS) in the recovery room immediately following surgery and
      at 4, 10, and 24 hours thereafter. RESULTS: The overall incidence of STP in
      patients undergoing laparoscopic procedures was approximately 24%. Twenty-one
      patients (42%) in the control group and 4 patients (7%) in the treatment group
      complained of shoulder pain during the recording period (P = 0.003). Mean STP
      scores as recorded on VAPS were significantly lower in the bupivacaine group than
      in the control group from 4 to 24 hours after surgery (P < 0.01). Postoperative
      analgesia requirements were also significantly reduced in those patients
      receiving bupivacaine irrigation (P < 0.04). CONCLUSION: Intraperitoneal
      irrigation with bupivacaine to both hemidiaphragms at the end of surgery
      significantly reduces both frequency and intensity of STP following laparoscopic
      procedures thus reducing patient morbidity.

PMID- 9776155
TI  - The accuracy of laparoscopic ultrasound in the detection of colorectal cancer
      liver metastases.
AB  - BACKGROUND: The most sensitive and specific method of detecting colorectal cancer
      hepatic metastases has been shown to be a combination of careful intraoperative
      palpation and intraoperative ultrasound. Although there has been growing interest
      in laparoscopic surgical therapy for colorectal cancer, the ability of this
      technique to adequately evaluate the liver for small metastases has been unknown.
      This study was undertaken to compare laparoscopic liver ultrasound to the gold
      standard of open palpation and intraoperative ultrasound in detecting hepatic
      metastases from colorectal cancer. METHODS: A preliminary animal model was first
      performed in adult pigs. Eighteen liver "lesions" were created with chlorhexidine
      gluconate under laparoscopic guidance. A blinded surgeon then performed
      laparoscopic liver ultrasound followed by open ultrasound and palpation,
      comparing the accuracy of these techniques in detecting the lesions. In a second
      study, 15 patients undergoing laparotomy for colorectal cancer underwent
      preliminary laparoscopic liver ultrasound followed by open palpation and
      intraoperative ultrasound to compare these methods of liver evaluation. RESULTS:
      Laparoscopic liver ultrasound detected 17 of 18 lesions created in the pig
      livers, for a sensitivity of 94.4%. There were two false negatives, for a
      specificity of 77.7%. Laparoscopic liver ultrasound detected 4 of the 5 liver
      metastases in the human study, for a sensitivity of 80%. There was a single false
      negative, for a specificity of 90.9%. Several technical difficulties and their
      solutions are discussed. CONCLUSIONS: With several technical modifications guided
      by our initial experience, we believe laparoscopic liver ultrasound can be an
      effective way of evaluating the liver for metastases during laparoscopic
      colorectal resection for cancer.

PMID- 9776156
TI  - Colon carcinoma in patients undergoing liver transplantation.
AB  - BACKGROUND: Organ recipients are at risk for certain neoplasms. Ulcerative
      colitis (UC) is itself a strong risk factor for the development of colon
      carcinoma (CCa). Transplant patients with UC might be at higher risk for CCa. We
      analyzed these patients to compare the incidence and pattern of CCa development
      in these and non-UC patients following liver transplantation (OLTX). PATIENTS AND
      METHODS: Retrospective study of 1,085 OLTX patients. RESULTS: In 1,022 patients
      without UC, 1 patient (< 0.1%) developed adenocarcinoma in a colonic polyp 46
      months after OLTX. Sixty-three of 108 (60%) patients undergoing OLTX
      simultaneously had UC. Five OLTX patients (8%) with UC developed colon
      adenocarcinoma 22 to 66 (mean 48) months after OLTX. Two have died. CONCLUSIONS:
      Coexistent UC in patients requiring OLTX constitutes a potentially high risk for
      the development of colonic cancer, a late-appearing event. These patients require
      close observation and frequent colonoscopic/histologic screening of the colon.

PMID- 9776157
TI  - Duct-parenchymal ratio predicts exocrine pancreatic function after
      pancreatoduodenectomy and distal pancreatectomy.
AB  - BACKGROUND: The postoperative exocrine pancreatic function was compared between
      pancreatoduodenectomy and distal pancreatectomy, and we studied the relationship
      between the preoperative morphology of the pancreas expected to remain and
      pancreatic function after surgery. PATIENTS AND METHODS: In 27 patients who
      underwent pylorus-preserving pancreatoduodenectomy (PPPD group) and 12 who
      underwent distal pancreatectomy (DP group), the exocrine pancreatic function was
      assessed using the BT-PABA excretion test before surgery and short term after
      surgery (< or =2 months). Preoperative morphology of the pancreas at a presumed
      line of transection was also investigated on computed tomography. RESULTS: The
      mean urinary PABA excretion rate in the PPPD group decreased from 68.3% to 53.7%
      (P = 0.0029), whereas that in the DP group showed no significant change (70.7%
      versus 72.7%). The mean size of the main pancreatic duct at the presumed
      transection line in the PPPD group was significantly greater than that in the DP
      group (6.5 mm versus 2.6 mm, P = 0.0002). The mean parenchymal thickness of the
      pancreatic gland at the presumed transection line in the PPPD group was
      significantly smaller than that in the DP group (16.1 mm versus 18.6 mm, P =
      0.04). The mean ratio of the pancreatic duct caliber to parenchymal thickness
      (duct-parenchymal ratio) in the PPPD group was significantly higher than that in
      the DP group (0.43 versus 0.14, P = 0.0004). There was a significant negative
      correlation between the postoperative PABA excretion rate and the duct
      parenchymal ratio (P = 0.0057). CONCLUSIONS: The postoperative exocrine
      pancreatic function after PPPD and DP was significantly influenced by the
      morphology of the pancreas at the presumed transection line. It is important to
      evaluate the preoperative morphology of the presumably remaining pancreas,
      especially duct-parenchymal ratio, to predict the exocrine pancreatic function
      short term after pancreatectomy.

PMID- 9776158
TI  - Pancreaticogastrostomy for reconstruction of pancreatic stump after
      pancreaticoduodenectomy for ampullary carcinoma.
AB  - BACKGROUND: Management of the pancreatic stump after pancreaticoduodenectomy (PD)
      is still a matter of debate. Pancreaticojejunostomy (PJ) is used commonly but is
      associated with a significant incidence of pancreatic leaks.
      Pancreaticogastrostomy (PG) is an alternative that has been reported to be safer.
      METHODS: The study is a retrospective analysis of all patients having PD for
      ampullary carcinoma in one surgical unit at All India Institute of Medical
      Sciences over 18 years, with PG being the only drainage procedure for the
      pancreatic stump. RESULTS: Among 125 patients having PD for ampullary carcinoma,
      overall morbidity rate was 28%, mortality rate was 4.8%, with no cases of leakage
      from the pancreaticogastrostomy. CONCLUSIONS: In world literature (including the
      current series), the leakage rate of PG is 2.5% (14 of 553) with only 2 deaths (2
      of 14) due to leakage from PG. Our large experience and these data conclusively
      prove the safety of pancreaticogastrostomy, which should be the drainage
      procedure of choice for the pancreatic stump following pancreaticoduodenectomy.

PMID- 9776159
TI  - A new evaluation of pancreatic function after pancreatoduodenectomy using
      secretin magnetic resonance cholangiopancreatography.
AB  - BACKGROUND: The remnant pancreatic function after pancreatoduodenectomy
      influences greatly postoperative quality of life. However, it has been difficult
      to evaluate the exocrine remnant pancreatic function postoperatively. The aim of
      this study was to assess the usefulness of secretin-stimulated magnetic resonance
      cholangiopancreatography (secretin MRCP) in evaluating the remnant pancreatic
      function and ascertaining the anastomotic patency after pancreatoduodenectomy.
      METHODS: Thirty-four patients who underwent pancreatoduodenectomy were evaluated
      with secretin MRCP. The results of MRCP were determined by the amount of exocrine
      pancreatic secretion, and were graded as follows: grade I (poor secretion), grade
      II (moderate secretion), and grade III (good secretion). RESULTS: Secretin MRCP
      could visualize the pancreatic secretion dynamically. MRCP grades were grade I in
      11 patients, grade II in 12, and grade III in 11. There was a significant
      correlation between MRCP grade and glucose tolerance. We confirmed visually the
      patency of the anastomotic site in 24 patients (71%). MRCP grades correlated
      significantly with clinical symptoms. CONCLUSION: Our results demonstrated
      secretin MRCP was feasible for evaluating the remnant pancreatic function after
      pancreatoduodenectomy.

PMID- 9776160
TI  - The futility of chest roentgenograms following routine central venous line
      changes.
AB  - OBJECTIVE: To demonstrate chest roentgenograms after central venous line changes
      over a guidewire delay the use of the central lines and increases charges with no
      change of morbidity or the rate of complication. METHODS: Retrospective study
      using the Surgical Intensive Care database followed by a nonrandomized,
      prospective study of central venous line changes. The total time from the
      catheter change until chest radiograph confirmation and an analysis of charges
      was done. RESULTS: The retrospective study of 1,201 central line changes
      demonstrated no pneumothorax and two central lines malpositioned. The prospective
      study of 100 patients demonstrated no pneumothorax and one catheter
      malpositioned. The average time from completion of the central line change until
      the radiographic confirmation was 60.2 minutes. The charge for the chest x-ray
      film was $156. CONCLUSIONS: The combined studies composed of 1,301 patients
      demonstrated no pneumothorax and three malpositioned catheters. This study
      demonstrates that radiographic confirmation of central venous line placement
      after routine line change is of no benefit as the malpositioned catheters caused
      no morbidity, produces significant delays and increases medical charges to the
      patient. Extrapolation predicts an annual reduction of $46,800 in the Vanderbilt
      Surgical Intensive Care Unit.

PMID- 9776161
TI  - The significance of histologically infiltrated resection margin after
      esophagectomy for esophageal cancer.
AB  - BACKGROUND: Microscopic tumor infiltration of the resection margin after
      esophageal resection is implicated to influence anastomotic leakage, tumor
      recurrence rates, and long-term survival. METHODS: Patients with tumor
      infiltration of resection margin (RM+) and those without (RM-) were compared.
      RESULTS: Of 604 patients, 45 (7.5%) were RM+. Patients in the RM+ group had more
      palliative resections, 76% versus 56%, P = 0.01. Anastomotic leakage rates were
      2.2% (RM+) and 4.1% (RM-), P = 1.0. Excluding hospital deaths, anastomotic
      recurrences developed in 10.3% in the RM+ group and 4.9% in the RM- groups, P =
      0.15. Although a positive margin did not increase anastomotic recurrence, a
      shorter resection margin correlated with such recurrence. The mean (SEM) lengths
      of resection margins in surgical specimens were 2.7 cm (0.3) and 4.4 cm (0.1) for
      those with and without recurrence, P < 0.001. Median survival time were 8.8
      months (RM+) and 15 months (RM-), P = 0.007. CONCLUSIONS: Histologic infiltration
      of resection margins did not influence leakage rate. Anastomotic recurrence was
      related to the length of resection margin.

PMID- 9776162
TI  - Evaluation of abdominal pain in systemic lupus erythematosus.
AB  - BACKGROUND: Abdominal pain is a common finding in patients with systemic lupus
      erythematosus (SLE), occurring in as many as half of all SLE patients in the
      course of their disease. The rheumatology and gastroenterology literature
      emphasizes etiologies of abdominal pain in patients with SLE such as peritonitis
      from polyserositis, dyspepsia from reflux, nausea and vomiting from bowel edema,
      ascites, mesenteric ischemia, pancreatitis, pneumatosis intestinalis from
      necrotizing enterocolitis, and hepatobiliary abnormalities. But in clinical
      practice, caring for SLE patients in a community teaching hospital, these seem to
      be rare entities. PATIENTS AND METHODS: A chart review study was performed of all
      patients with SLE with the diagnosis of abdominal pain admitted to a community
      teaching hospital between 1980 and 1995. RESULTS: Of 13 patients who presented
      with abdominal pain, 9 required surgical intervention for cholecystitis,
      perforated ulcer, colonic perforation, diverticulitis, and adhesions. There were
      no negative laparotomies for polyserositis or bowel edema, or cases of mesenteric
      infarction or ascites. CONCLUSION: Despite some unusual diagnostic possibilities
      in abdominal pain in SLE such as polyserositis and mesenteric infarction, and
      despite the superimposed problems of steroid therapy in most of the patients in
      this study, the majority of lupus patients with abdominal pain presenting at
      community hospitals have relatively conventional illnesses.

PMID- 9776163
TI  - Reconstruction of the hepatic and portal veins using a patch graft from the right
      ovarian vein.
AB  - We describe a patch-graft technique using the right ovarian vein for
      reconstruction of the right hepatic and portal veins after resection in
      hepatectomy and pancreatoduodenectomy in female patients. After partial resection
      of the right hepatic vein or portal vein for removing either hepatic or
      pancreatic tumors, the defects were covered by a patch graft from the right
      ovarian vein. The proximal part of the vein, 5 cm in length, was harvested,
      divided longitudinally, and then divided into two equal parts, which were sutured
      together to give a patch measuring 2.5 x 2.0 cm. This technique can be applied
      for reconstruction after partial resection of the hepatic or portal vein in
      hepatectomy and pancreatoduodenectomy.

PMID- 9776165
TI  - Helpful techniques to facilitate abdominal procedures.

PMID- 9776164
TI  - Extended lymphadenectomy for thoracic esophageal cancer.

PMID- 9776166
TI  - Influenza and pneumococcal vaccination levels among adults aged > or =65 years-
      United States, 1997.
AB  - In 1996, influenza and pneumonia were the fifth leading cause of death among
      persons aged > or =65 years in the United States. A national health objective for
      2000 is to increase influenza and pneumococcal vaccination levels to > or =60%
      among persons at high risk for complications, including those aged > or =65
      years. To monitor states' progress toward achieving this objective, data from the
      1997 Behavioral Risk Factor Surveillance System (BRFSS) were analyzed. This
      report summarizes the BRFSS findings, which indicate the influenza vaccination
      objective was exceeded by 45 states and by the 50 states and the District of
      Columbia (DC) combined, but the pneumococcal vaccination objective was not
      reached by any state.

PMID- 9776167
TI  - Deaths resulting from residential fires and the prevalence of smoke alarms-
      United States, 1991-1995.
AB  - In 1995, residential fires accounted for an estimated 3600 deaths and
      approximately 18,600 injuries. In addition, property damage and other direct
      costs have been estimated to exceed more than $4 billion annually. To determine
      residential fire-related death rates, CDC analyzed death certificate data from
      1991 to 1995 from U.S. vital statistics mortality tapes. Data from CDC's
      Behavioral Risk Factor Surveillance System (BRFSS) was used to determine the
      prevalence of smoke alarms in U.S. households. This report presents the findings
      of these analyses, which indicate a seasonal variation in fire-related deaths and
      a high prevalence of smoke alarms in residences in the United States.

PMID- 9776168
TI  - Outbreak of cyclosporiasis--Ontario, Canada, May 1998.
AB  - During May-June 1998, the Ontario Ministry of Health and local health departments
      in Ontario received reports of clusters of cases of cyclosporiasis associated
      with events held during May. This report describes the preliminary findings of
      the investigation of a cluster in Toronto, Ontario, and summarizes the findings
      from investigations of 12 other clusters. These investigations indicated that
      fresh raspberries imported from Guatemala were linked to the multicluster
      outbreak.

PMID- 9776169
TI  - Local data for local decision making--selected counties, Connecticut,
      Massachusetts, and New York, 1997.
AB  - Although the delivery of clinical preventive services to adults, such as adult
      vaccinations and cancer and cardiovascular screening, reduces premature morbidity
      and mortality, such services are underused. Performance monitoring at the
      population level plays a critical role in supporting efforts to increase the use
      of clinical preventive services. However, many communities do not have the
      capacity to measure prevention activities. Without such information, efforts
      aimed at improving the county-wide or regional use of clinical preventive
      services must rely on state or national data. To examine the use of seven
      clinical preventive services among adults at the county level and to demonstrate
      how a population-based survey can be used to guide local prevention efforts, a
      community-based coalition (the Sickness Prevention Achieved through Regional
      Collaboration [SPARC]), in collaboration with state health departments, peer
      review organizations, and CDC, conducted a survey in the four-county SPARC
      region. This report summarizes the results of this analysis, which indicate that
      clinical preventive services in this region were underused despite high levels of
      access to medical care.

PMID- 9776170
TI  - Transgenic mutation models: research, testing, and reality checks.

PMID- 9776171
TI  - Transgenic animal models for mutagenesis studies: role in mutagenesis research
      and regulatory testing.

PMID- 9776172
TI  - The use of transgenic animals in research.

PMID- 9776173
TI  - Principles and practices of integrating genotoxicity evaluation into routine
      toxicology studies: a pharmaceutical industry perspective.
AB  - In this article, an integrated in vivo genotoxicity testing philosophy and a
      practical approach, as applied to pharmaceuticals, are described. Recently, there
      has been an effort to integrate the rodent (primarily rat) micronucleus assay
      with routine 2-4-week toxicokinetic studies. This approach has several
      advantages: 1) it utilizes the general principles of toxicology that govern the
      overall toxicity profile of a test substance; 2) factors such as the dose and/or
      route of drug administration, drug metabolism, principles of toxicokinetics, and
      saturation of defense mechanisms are considered in evaluating genotoxicity; 3) it
      uses the concept of administering multiple tolerable doses aiding in achieving
      steady state plasma drug levels, which is more relevant for risk assessment
      compared to high acute doses; and 4) it helps minimize the amount of drug, number
      of animals used, and other resources. This integration approach can be extended
      to other toxicology studies and other relevant genotoxicity endpoints may be
      assessed. Based on the experience in our laboratory, integrating micronucleus
      assessment in routine toxicology testing is promising and should be utilized when
      practical.

PMID- 9776174
TI  - Oxidative DNA damage and cytogenetic effects in flight engineers exposed to
      cosmic radiation.
AB  - This study set out to analyze biomarkers for genotoxic events, e.g., oxidative
      DNA damage, chromosomal damage and hprt mutations, among flight personnel, who
      are known to be occupationally exposed to ionizing radiation of cosmic origin.
      Twenty-three flight engineers were recruited while ground personnel served as a
      matched control group. Cumulative radiation doses during flight were calculated
      on the basis of subjects' flight records assuming an exposure rate of 6 microSv
      per hour of flight. Oxidative DNA damage in peripheral lymphocytes from flight
      engineers appeared significantly increased in comparison with controls and was
      associated with cumulative exposure to cosmic radiation. Frequencies of
      peripheral lymphocyte chromosome aberrations, micronuclei and hprt mutations
      appeared also to be increased in flight engineers, but not significantly. It was
      also observed that DNA damage was higher in flight engineers with a relatively
      shorter flight history in comparison with flight engineers with higher cumulative
      exposures to radiation, suggesting adaptation to DNA damage caused by ionizing
      radiation. DNA repair activities measured as unscheduled DNA synthesis were
      clearly increased in the higher-exposed subgroup of flight engineers, and
      appeared significantly correlated with cumulative radiation dose, as well as
      inversely with oxidative DNA damage. The implications for cancer risk assessment
      in relation to exposure to cosmic radiation are discussed.

PMID- 9776176
TI  - Chronic ingestion of clastogens by mice and the frequency of chromosome
      aberrations.
AB  - Environmental exposure to mutagens is believed to play a significant role in
      human carcinogenesis. Determination of the in vivo effects of a single mutagen is
      best done in laboratory animals because humans are exposed to a variety of
      mutagens both in their diet and in the rest of their environment. In this study,
      C57BL/6N female mice were used to analyze the effect on chromosomes of chronic
      ingestion of a mutagen dissolved in drinking water. Cyclophosphamide (CP) or
      urethane (ethyl carbamate, EC) were dissolved in sterile drinking water at
      concentrations of 0, 32, 64, and 96 ppm or 0, 5,000, 10,000, and 15,000 ppm,
      respectively. All exposures began at 8 weeks of age and continued through the
      20th week unless terminated earlier due to toxicity. Body weights and water
      consumption were measured weekly. Blood and bone marrow were taken from
      approximately five mice per exposure group at 4, 8, and 12 weeks from the start
      of exposure. All mice remaining after 12 weeks received drinking water without
      any carcinogen for an additional 6 weeks to determine if induced aberrations
      persisted. Chromosome translocations, measured by painting, were not induced in
      blood or bone marrow cells at any time point for either chemical. However, both
      carcinogens induced significant increases in micronucleated normochromatic
      erythrocytes, indicating that the carcinogens reached the tissues examined in
      these experiments. These results indicate that chronic exposure of mice to
      chemical carcinogens induces chromosome breakage measurable by micronuclei.
      However, the breakage and reunion necessary to see chromosome exchanges such as
      translocations were not observed in this study.

PMID- 9776175
TI  - Genetic effects of petroleum fuels: II. Analysis of chromosome loss and
      hyperploidy in peripheral lymphocytes of gasoline station attendants.
AB  - Molecular cytogenetic methods were applied to investigate the effect of the
      occupational exposure to low concentrations of benzene and petroleum fuels on
      genomic stability. Twelve male gasoline station attendants (average benzene
      exposure of 0.32 mg/m3 as 8h TWA) and 12 age- and smoking-matched unexposed
      controls were selected for the study. The incidence of hyperploidy and polyploidy
      in peripheral lymphocytes was evaluated through in situ hybridization of
      interphase cells, harvested 24 hr after stimulation, with centromeric probes of
      chromosomes 7, 11, 18, and X. For half of the subjects, metaphases harvested 24
      hr later were analyzed. The incidence of chromosome loss in vitro was determined
      in cytokinesis-blocked cells, harvested at 66 hr, through the hybridization of
      micronuclei with a pancentromeric probe. Ten thousand chromosomes (more than 200
      metaphases equivalent) and 2,000 binucleated cells/person were scored for
      hyperploidy and micronucleus analysis, respectively. The results obtained did not
      show any exposure-related excess of hyperploidy or micronucleus formation.
      Conversely, the age of the subjects was significantly correlated with several
      markers of genomic instability, such as the incidence of chromosome X and
      chromosome 18 hyperploidy, total hyperploidy and polyploidy, and close to
      statistical significance with chromosome loss. Smoking habits did not appear to
      contribute significantly to the effects measured. The parallel analysis of
      hyperploidy and polyploidy in interphase nuclei in 24-hr cultures and in
      metaphase cells harvested 24 hr later showed basically similar incidences of
      aneuploid cells, indicating that no significant selection against hyperploid and
      polyploid types occurred during the first cell cycle in vitro.

PMID- 9776177
TI  - High sensitivity for color mutants in lacZ plasmid-based transgenic mice, as
      detected by positive selection.
AB  - Transgenic mice carrying bacteriophage lambda-based vectors harboring a lacZ or
      lacI reporter gene have been used in recent years for the detection,
      quantification, and characterization of spontaneous and induced gene mutations in
      vivo. The usefulness of these models is basically determined by their ability to
      detect significant (organ-specific) exposure-related increases in mutant
      frequencies. This, in its turn, is dependent on the models' ability to detect all
      possible types of mutations, including mutations that partially inactivate the
      gene product, as well as the absence of a significant proportion of E. coli
      derived mutations. The newly developed lacZ plasmid-based transgenic mouse
      mutation assay is sensitive to a broad range of DNA mutations, including large
      size changes. Here, we describe the plasmid model's sensitivity for detecting
      color mutants, i.e., cells containing a partially inactivated lacZ gene, as
      detected by a positive selection system using phenyl-beta-galactoside. The
      proportion of color mutants in brain and kidney was 30-40%. This was
      significantly higher than the 10-20% color mutants observed in lung, spleen, and
      liver. It is demonstrated that the color mutants detected were neither the result
      of a mixture of both mutant and nonmutant cells within the original mutant colony
      forming unit nor due to the presence of mutant and nonmutant lacZ genes within
      individual E. coli host cells. Sequence analysis of 13 different color mutants
      revealed single basepair substitutions in the lacZ gene of each mutant. The high
      tolerance of the positive selection system for lacZ color mutants in the plasmid
      based transgenic mouse model greatly contributes to the sensitivity of this
      model, now ranging from large size-change mutations that completely inactivate
      the lacZ gene to basepair substitutions that partly inactivate the lacZ gene.

PMID- 9776178
TI  - Formation of DNA adducts in tissues of mouse progeny through transplacental
      contamination and/or lactation after administration of a single dose of
      ochratoxin A to the pregnant mother.
AB  - Ochratoxin A (OTA) is a mycotoxin which has been detected in foods of plant
      origin, in edible animal tissues, and in human sera, urine, and milk in many
      countries. OTA is nephrotoxic and carcinogenic in mice and rats and is suspected
      to play a key role in the etiology of Balkan endemic nephropathy and/or
      associated urinary tract tumors. In the present study, some early signs of
      genetic impairment, including the presence of DNA adducts in target tissues from
      the progeny of mice after administration of a single OTA dose during late
      pregnancy, have been investigated. By the 32P-postlabeling method, several
      characteristic DNA adducts with the same Rf values were detected in kidney and
      liver of both the OTA-treated mice and their progeny the fetus and the offspring.
      No adduct was found in tissues from control animals. Different adducts were most
      important in kidney and liver DNA and some were organ-specific. High levels of
      DNA adducts were detected in the kidneys of male progeny, whereas in the female
      progeny and the mothers they were detected almost exclusively in the liver. This
      result correlates well with the carcinogenicity in mice: the target organ for
      males is the kidney, while for females it is the liver. High levels of DNA
      adducts were also found in fetuses. These results provide evidence for a direct
      genotoxic action of OTA in the progeny through transplacental contamination,
      which constitutes a new serious health hazard of exposure to this toxin.

PMID- 9776179
TI  - Relative activities of methyl methanesulphonate (MMS) as a genotoxin, clastogen
      and gene mutagen to the liver and bone marrow of MutaMouse mice.
AB  - The mutagenicity of the rodent carcinogen methyl methanesulphonate (MMS) to the
      liver and bone marrow of MutaMouse lacZ- transgenic mice was evaluated. A single
      intraperitoneal (i.p.) dose of 100 mg/kg MMS gave a strong positive response in
      the liver UDS and bone marrow micronucleus assays conducted 2 hr and 30 hr,
      respectively, after dosing. A single i.p. administration of 100 mg/kg of MMS, or
      five daily administrations of 20 mg/kg MMS, failed to increase significantly the
      lacZ- --> lacZ+ mutation frequency (MF) in either the liver or the bone marrow,
      albeit some evidence of weak mutagenicity was observed for the liver. The gene
      mutation analyses were undertaken 14 days after the final chemical exposure.
      Administration of the liver mitogens dimethylnitrosamine (DMN), or 4
      acetylaminofluorene (4AAF), subsequent to multiple (five) exposures of 20 mg/kg
      MMS, foiled to enhance the mutagenicity of MMS to the liver, thereby eliminating
      the possibility that MMS produced promutagenic lesions in the liver that were not
      transformed to mutations because of the absence of MMS-induced cell division. In
      the latter experiments, DMN gave a strong mutagenic response and 4AAF a weak
      mutagenic response. Possible reasons for this selective mutagenicity of MMS (DNA
      damage and micronuclei induction in the absence of gene mutations) are discussed,
      but no clear outcome emerges. It is concluded that transgenic mutation assays
      should not be employed for defining genetic toxicity in vivo, but rather should
      be reserved for mechanistic studies on previously established rodent genotoxins
      and/or carcinogens.

PMID- 9776182
TI  - Lack of induction of micronuclei in bone marrow erythrocytes of rats exposed to 3
      chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) for two years in a
      carcinogenicity bioassay.

PMID- 9776180
TI  - Defects in base excision repair combined with elevated intracellular dCTP levels
      dramatically reduce mutation induction in yeast by ethyl methanesulfonate and N
      methyl-N'-nitro-N-nitrosoguanidine.
AB  - Previously, we determined that elimination of deoxycytidylate (dCMP) deaminase
      (DCD1) in the yeast Saccharomyces cerevisiae increases the intracellular
      dCTP:dTTP ratio and reduces the induction of G x C --> A x T transitions in the
      SUP4-o gene by ethyl methanesulfonate (EMS) and N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG). Simultaneously, the G x C --> C x G transversion
      frequency rises substantially. We attributed the first response to dCTP
      outcompeting dTTP for incorporation opposite O6-alkylguanine, and the second
      outcome to the increased dCTP pool causing error-prone repair of apurinic (AP)
      sites resulting from the removal or lability of N7-alkylguanine. To test the
      latter hypothesis, we used isogenic dcd1 strains deleted for either of two genes
      (MAG1: 3-methyladenine glycosylase; APN1: apurinic endonuclease) involved in the
      repair of N7-alkylguanine. In these backgrounds, EMS or MNNG induction of total
      SUP4-o mutations, G x C --> A x T transitions and G x C --> C x G transversions
      were reduced by >98%, >97%, and >80%, respectively. Mutation frequencies in the
      dcd1 apn1 strain were close to those for spontaneous mutagenesis in the wild-type
      parent. These findings argue that misincorporation of dCTP during repair of
      alkylation-induced AP sites is responsible for the increased G x C --> C x G
      transversion frequency in the dcd1 strain treated with EMS or MNNG. The data also
      demonstrate that defective repair of AP sites coupled with an elevated dCTP:dTTP
      ratio eliminates most EMS and MNNG mutagenesis. In addition, the results point to
      a role for AP sites in the production of some EMS- and MNNG-induced G x C --> A x
      T transitions as well as other substitutions in the dcd1 strain.

PMID- 9776181
TI  - In vivo studies on genotoxicity of a soil fumigant, dazomet.
AB  - Dazomet is a soil fumigant effective against germinating weed seeds, nematodes,
      soil fungi, and soil insects. Dazomet is primarily used for preplanting control
      in tobacco and forest nursery crops and is now marketed for a wider range of open
      field and greenhouse crops (e.g., vegetables, fruits, ornamental plants, lawns,
      and turfs). Swiss CD1 male and female mice were intraperitoneally treated with
      dazomet in order to evaluate its potential genotoxicity. DNA damage activity,
      namely, DNA single-strand breaks, DNA adducts, and increased micronuclei
      frequency due to treatment with the soil fumigant was observed in the
      experimental animals. Dose-dependent DNA adduct formation was detected in the
      liver, kidneys, and lungs of mice. DNA adduct levels in these three organs were
      6.0 +/- 0.4 (SD), 4.8 +/- 0.1 (SD), and 2.2 +/- 0.4 (SD) adducts/10(8)
      nucleotides, respectively, at the highest dose of the soil fumigant tested (90
      mg/kg). No adduct formation was observed in control mice. A significant increase
      in DNA single-strand breaks was detected in the liver and kidneys of mice treated
      with 100 mg/kg of dazomet (P < 0.05). A significant increase in micronuclei
      frequency was observed in the bone marrow of mice treated with 100 mg/kg of
      dazomet (P < 0.05).

PMID- 9776183
TI  - Transition mutations at CpG dinucleotides are the most frequent in vivo
      spontaneous single-based substitution mutation in the human HPRT gene.

PMID- 9776184
TI  - Selection of agar for use in Salmonella typhimurium and Escherichia coli mutation
      assays.
AB  - The spontaneous and induced revertant frequency of four Salmonella typhimurium
      strains (TA1535, TA1537, TA98, and TA100) and Escherichia coli [WP2 uvrA
      (pKM101)] was evaluated using Vogel Bonner minimal plates prepared with ten
      different agars. In addition to the Difco Bacto agar originally recommended by
      Ames, Difco Noble, granulated and Bitek agars; BD grade A, BBL granulated and
      purified agars; Oxoid purified and No. 1 agars; and GIBCO select agar were
      tested. Several of these agars have been reported as acceptable alternatives for
      these Salmonella strains, but comparable studies with E. coli have not been done.
      The bacteria were treated with DMSO or an appropriate positive control in the
      presence or absence of an Aroclor 1254-induced rat liver activation system. With
      the exception of Noble agar in the presence of S9, there was little difference
      among the responses of the Salmonella strains on any of the agars. However, with
      E. coli the responses include either a reduction or an increase in spontaneous
      revertants numbers as well as a reduction in absolute and relative induced
      revertant frequency. Difco Bacto agar appears to be the most consistent agar for
      use with these strains. As an alternative, only BBL purified agar resulted in
      consistent results for all of these strains under all testing conditions. These
      results emphasize the need to evaluate the components of the standard mutation
      assay when incorporating additional bacterial strains. Suboptimal responses
      related to the agar or other components could compromise the detection of weak
      mutagens.

PMID- 9776185
TI  - A tissue-engineered conduit for peripheral nerve repair.
AB  - BACKGROUND: Peripheral nerve repair using autograft material has several
      shortcomings, including donor site morbidity, inadequate return of function, and
      aberrant regeneration. Recently, peripheral nerve research has focused on the
      generation of synthetic nerve guidance conduits that might overcome these
      phenomena to improve regeneration. In our laboratory, we use the unique chemical
      and physical properties of synthetic polymers in conjunction with the biological
      properties of Schwann cells to create a superior prosthesis for the repair of
      multiply branched peripheral nerves, such as the facial nerve. OBJECTIVES: To
      create a polymeric facial nerve analog approximating the fascicular architecture
      of the extratemporal facial nerve, to introduce a population of Schwann cells
      into the analog, and to implant the prosthesis into an animal model for
      assessment of regeneration. RESULTS: Tubes of poly-L-lactic acid (molecular
      weight, 100000) or polylactic-co-glycolic acid copolymer were formed using a dip
      molding technique. They were created containing 1, 2, 4, or 5 sublumina, or
      "fascicular analogs." Populations of Schwann cells were isolated, expanded in
      culture, and plated onto these polymer films, where they demonstrated excellent
      adherence to the polymer surfaces. Regeneration was demonstrated through several
      constructs. CONCLUSIONS: A tubular nerve guidance conduit possessing the
      macroarchitecture of a polyfascicular peripheral nerve was created. The
      establishment of resident Schwann cells onto poly-L-lactic acid and polylactic-co
      glycolic acid surfaces was demonstrated, and the feasibility of in vivo
      regeneration through the conduit was shown. It is hypothesized that these tissue
      engineered devices, composed of widely used biocompatible, biodegradable polymer
      materials and adherent Schwann cells, will be useful in promoting both more
      robust and more precisely directed peripheral nerve regeneration.

PMID- 9776187
TI  - Alloantigen gene therapy for squamous cell carcinoma of the head and neck:
      results of a phase-1 trial.
AB  - OBJECTIVE: To determine the safety and efficacy of an immunogenic gene therapy
      using a drug designed to produce expression of a foreign class I major
      histocompatibility complex protein in patients with head and neck cancer. DESIGN:
      Phase 1 prospective clinical trial. SETTING: Academic medical setting. PATIENTS:
      Nine patients with advanced head and neck squamous cell carcinoma who had failed
      conventional therapy and did not express HLA-B7, a class I major
      histocompatibility complex protein. INTERVENTION: Patients were treated with
      Allovectin-7 (Vical Inc, San Diego, Calif) by direct intratumoral injection.
      Allovectin-7 contains a plasmid complementary DNA complexed with a cationic
      lipid, which results in expression of HLA-B7. MAIN OUTCOME MEASURES: Patients
      were assessed for any toxic effects and for any change in tumor volume. Biopsy
      specimens obtained before and after therapy were evaluated by
      immunohistochemistry to detect HLA-B7 expression and with the terminal
      deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end
      labeling (TUNEL) assay to detect any induction of apoptosis. RESULTS: There were
      no toxic effects of the gene therapy. In 4 of these 9 patients there was a
      partial response to treatment, evidenced by a gradual reduction in tumor size.
      One patient has remained alive for more than 17 months since commencing
      treatment, with no clinical evidence of disease but with persistent histological
      evidence of cancer. Analysis of the biopsy specimens from 2 of the patients who
      responded to therapy demonstrated HLA-B7 expression. The TUNEL assay demonstrated
      extensive apoptosis in both of these patients, suggesting that this may be the
      mechanism of tumor reduction. CONCLUSIONS: These data demonstrate the potential
      efficacy and lack of toxicity of this form of alloantigen gene therapy. A multi
      institutional study has been initiated to expand on these findings.

PMID- 9776188
TI  - Starplasty: a new technique of pediatric tracheotomy.
AB  - OBJECTIVE: To report a new technique of pediatric tracheotomy that reduces the
      problems of pneumothorax and recannulation after accidental decannulation in a
      recently performed tracheotomy. DESIGN: Retrospective chart review for 1990-1997.
      PATIENTS: Sixty-eight children aged between 2 days and 14 years. METHOD: The
      starplasty procedure is based on the geometry of a 3-dimensional Z-plasty. The
      technique of the procedure is described and illustrated in detail. RESULTS: There
      were 27 short-term complications, including 4 accidental decannulations. There
      were no instances of pneumothorax or tracheotomy-related deaths. There were 25
      long-term minor complications. There were no instances of tracheotomy-related
      death, suprastomal collapse, or tracheal stenosis. Thirty-eight children remain
      tracheotomy tube dependent, 17 underwent decannulation, 7 died of primary
      disease, and 6 were lost to follow-up. All 17 children who underwent
      decannulation have a persistent tracheocutaneous fistula. CONCLUSIONS: I conclude
      that starplasty reduces the incidence of major complications and death. Its only
      drawback seems to be persistent tracheocutaneous fistula.

PMID- 9776186
TI  - Clinical outcome of endoscopic surgery for frontal sinusitis.
AB  - OBJECTIVE: To determine the efficacy of endoscopic surgery for chronic frontal
      sinusitis. DESIGN: A prospective analysis of established measures of clinical
      outcome (Chronic Sinusitis Survey and Short Form 36) that was administered to
      patients before frontal sinus surgery and at intervals of 3 months, 6 months, and
      1 year after surgery. INTERVENTIONS: For limited disease, the frontal recess was
      opened and the frontal ostium probed or enlarged. For more severe cases, a drill
      was used to resect the frontal sinus floor and interfrontal septum. SETTING:
      Private and institutional-based practices at an academic medical center.
      SUBJECTS: Eighty-seven patients who underwent endoscopic surgery for frontal
      sinusitis, including 24 patients with severe disease who underwent a frontal
      sinus drillout procedure. MAIN OUTCOME MEASURES: Scores on the Chronic Sinusitis
      Survey, Short Form 36, and surgical revision rate. RESULTS: Significant
      improvement in facial pain, nasal drainage, and congestion was observed 1 year
      after surgery (P<.01). Medication use was also significantly reduced during this
      period (P<.01). Quality-of-life measures showed greatest improvement in the
      domain of social functioning (P<.05). Three (12.5%) of 24 patients who underwent
      a frontal sinus drillout procedure did not respond to surgery secondary to
      restenosis of the frontal ostium. CONCLUSIONS: Although the long-term results of
      endoscopic surgery for frontal sinusitis are unknown, this approach appears to be
      effective for most patients and may provide a reasonable alternative to frontal
      sinus obliteration surgery in selected cases.

PMID- 9776189
TI  - Bronchoscopy and laryngoscopy findings as indications for tracheotomy in the
      burned child.
AB  - OBJECTIVE: To determine possible indications for tracheotomy in the burned child
      based on bronchoscopic and laryngoscopic findings. DESIGN AND SETTING: A
      retrospective case study of all patients admitted to a tertiary children's burn
      center. PARTICIPANTS: All children admitted with burn inhalation injury between
      1990 and 1995 (n = 211). INTERVENTION: All patients underwent laryngoscopy and
      bronchoscopy and 19 underwent tracheotomy, with 5 tracheotomy tubes placed
      emergently. MAIN OUTCOME MEASURES: Observations during laryngoscopy and
      bronchoscopy included erythema, edema, carbonaceous material, ulcerations, and
      bronchial mucous casts. The supraglottis, glottis, and subglottis were analyzed
      separately, when possible. Any sepsis resulting from tracheotomy was determined.
      Complications, such as glottic webs, subglottic stenosis, and tracheomalacia,
      were noted. RESULTS: Indications for tracheotomy included 6 for airway
      obstruction, 6 for prolonged intubation, 6 for pulmonary cleansing, and 1 for
      endotracheal tube complications (subglottic stenosis). When examined by
      bronchoscopy and laryngoscopy, 17 of 19 children had significant airway edema, 10
      had carbonaceous material in the airway, and 3 had ulcerations in the airway.
      CONCLUSIONS: Tracheotomy is indicated in the burned child when significant airway
      edema is present. Failure to place a tracheotomy tube in these cases leads to a
      high incidence of immediate tracheotomies (26%). There was no evidence of
      clinically significant infection attributable to tracheotomy. The number of
      airway complications due to tracheotomy was no higher than from endotracheal
      intubation.

PMID- 9776190
TI  - Tympanostomy tubes and water exposure: a practical model.
AB  - OBJECTIVE: To determine whether water exposure causes middle ear contamination in
      patients with collar button tympanostomy tubes (TTs). METHOD AND DESIGN: An in
      vitro model of a human head that contained an auricle, external auditory canal,
      tympanic membrane with TT, middle ear, eustachian tube, and mastoid cavity was
      developed. Two electrodes connected to an external ohmmeter resided in the middle
      ear to detect water entry. The model was tested with 4 types of water exposure:
      showering, bathing, hair rinsing, and swimming. Statistical analysis was
      performed by the Fisher exact test. MAIN OUTCOME MEASURES: A positive test result
      corresponded to water entering the middle ear via the TT, confirmed by a
      resistance reading of zero on the ohmmeter. A negative test result indicated no
      change in the initial high resistance reading. RESULTS: No positive test results
      were obtained for showering (0 of 60 tests), hair rinsing (0 of 60 tests), or
      head submersion (12.7 cm) in clean tap water (0 of 60 tests). Ten positive test
      results were obtained for head submersion in soapy water (10 of 97 tests), which
      was statistically different from clean water (P< or =.007). Swimming pool depths
      of 30, 45, 60, and 75 cm elicited positive test results in 2 of 16, 3 of 18, 2 of
      20, and 11 of 20 tests, respectively. A higher incidence of water entry into the
      middle ear occurred at depths of more than 60 cm (P< or =.001). No statistical
      difference between depths of 60 cm or less occurred (P= .88). CONCLUSIONS:
      Showering, hair rinsing, and head submersion in clean tap water do not promote
      water entry into the middle ear. Submersion in soapy water increases the
      probability of water contamination. Pool water infrequently enters the middle ear
      with head submersion, but the incidence increases with deeper swimming (>60 cm).
      These data provide further evidence that many water precautions frequently
      advised in patients with TTs are unnecessary.

PMID- 9776191
TI  - Extracranial repair of pediatric traumatic cerebrospinal fluid rhinorrhea.
AB  - OBJECTIVE: To examine the methods of extracranial repair of traumatic defects in
      the cribriform plate and ethmoid roof resulting in persistent cerebrospinal fluid
      (CSF) rhinorrhea in pediatric patients. DESIGN: Retrospective case series.
      SETTING: A single-institution, tertiary care, pediatric hospital. PATIENTS: Four
      children, ranging in age from 3 1/2 to 9 years, who sustained fractures in the
      cribriform plate or ethmoid roof. INTERVENTION: Transnasal endoscopic repair in 4
      patients, with 2 patients also undergoing external ethmoidectomy because of the
      large bony defect and the need for further exposure for repair. MAIN OUTCOME
      MEASURES: Time free from CSF leaks or recurrence, meningitis, and other
      postoperative complications. RESULTS: All patients except 1 have been free of
      recurrent CSF leaks, meningitis, and other postoperative complications. The 3
      patients who solely underwent the extracranial approach did not experience the
      complications of the traditional intracranial approach. CONCLUSIONS: In a select
      group of pediatric patients, the extracranial approach for the repair of CSF
      leaks is appropriate. Successful use of an extracranial approach in 3 of 4
      patients supports this method.

PMID- 9776192
TI  - Vagal paraganglioma: a review of 46 patients treated during a 20-year period.
AB  - BACKGROUND: Vagal paragangliomas (VPs) arise from paraganglia associated with the
      vagus nerve. Approximately 200 cases have been reported in the medical
      literature. Because of their rarity, most information regarding these tumors has
      arisen from case reports and small clinical series. OBJECTIVE: To detail the
      clinicopathologic features of 46 patients with VP with an emphasis on the role of
      a multidisciplinary skull base team in both the successful extirpation and
      rehabilitation. DESIGN: Retrospective review of 46 patients with VP managed by a
      single skull base team. SETTING: An academic tertiary medical center. RESULTS:
      Forty-six patients were treated over a 20-year period (1978-1998). Ten (22%)
      demonstrated intracranial extension. There was a history of familial
      paragangliomas in 9 (20%) of the patients. The incidence of multicentric
      paragangliomas was 78% in patients with familial paragangliomas vs 23% in
      patients with nonfamilial paragangliomas. Management of this group of 46 patients
      consisted of surgery (n = 40), radiation therapy (n = 4), and observation (n =
      2). The operative approach consisted of a transcervical excision often combined
      with a transtemporal or lateral skull base approach as dictated by the tumor
      extent. Postoperative cranial nerve deficits were common, and, as such,
      aggressive rehabilitation was a vital component in the management of these
      tumors. CONCLUSIONS: The management of VP and its associated cranial nerve
      deficits remains a difficult clinical problem. Options for treatment include
      surgical resection, radiation therapy, and, in selected cases, observation.
      Surgical extirpation requires a multidisciplinary skull base team to achieve
      complete tumor resection. Radiation therapy is reserved for elderly patients and
      patients at risk for bilateral cranial nerve deficits. Rehabilitation of cranial
      nerve deficits is an integral part of the management of VP.

PMID- 9776193
TI  - Percutaneous fluoroscopic gastrostomy tube placement in patients with head and
      neck cancer.
AB  - OBJECTIVE: To study the safety and efficacy of percutaneous fluoroscopic
      gastrostomy tube placement in patients with head and neck cancer. DESIGN: We
      conducted a retrospective case review of 92 consecutive cases. Comparable access
      procedures and relevant literature were reviewed. SETTING: Academic tertiary care
      center. PATIENTS: Patients with head and neck cancer who underwent percutaneous
      fluoroscopic gastrostomy tube placement between January 1996 and July 1996. MAIN
      OUTCOME MEASURES: Immediate, delayed, and long-term complications; tube
      malfunction; and tube placement failure. RESULTS: The major complication rate was
      1%; the minor complication rate was 8%; and the tube malfunction rate was 13%.
      The rate of successful tube placement was 98%. None of the patients required
      hospitalization as a result of the procedure. CONCLUSIONS: Percutaneous
      fluoroscopic gastrostomy tube placement is a safe, economical, and comfortable
      method that has distinct advantages over other gastrostomy tube placement
      methods. It is recommended for enteral feeding and nutritional supplementation in
      patients with head and neck cancer.

PMID- 9776194
TI  - Pharyngoesophageal reconstruction with the ulnar forearm flap.
AB  - OBJECTIVE: To evaluate the use of a generous fasciocutaneous ulnar forearm free
      flap in pharyngoesophageal reconstruction. DESIGN: Tertiary referral center.
      SETTING: Private practice. PATIENTS: From September 1, 1991, to October 30, 1996,
      20 ulnar forearm free flaps were used to reconstruct the pharyngoesophagus in 19
      patients after surgery for squamous cell carcinoma. There were 13 circumferential
      defects and 7 near-circumferential defects (<2 cm of mucosa remaining). The
      reconstructions were performed primarily (at the time of tumor resection) in 16
      cases and secondarily in 4 cases. INTERVENTION: A generous fasciocutaneous ulnar
      forearm flap with a minimum dimension of 9 x 22 cm was harvested to reconstruct
      the pharyngoesophagus. A 2-layer closure was performed in flap tailoring and
      proximal (pharynx to flap) and distal (flap to esophagus) anastomoses to minimize
      the risk of leakage. Also, portions of the flap were used to monitor flap
      viability, to cover cervical vessels, to obliterate dead space, and as skin
      coverage when the skin flaps were deficient. RESULTS: Nineteen of the 20 flaps
      transferred were successful. Swallow function was restored in 18 cases, and voice
      was rehabilitated in all the patients using either tracheoesophageal puncture and
      a voice device or an electrolarynx device. There was 1 perioperative mortality.
      Three fistulas occurred, all of which healed with nonsurgical treatment. One
      stricture developed that required intermittent dilatation. The donor site
      morbidity was minor. CONCLUSIONS: This versatile technique achieves excellent
      results with a decreased complication rate compared with other methods currently
      available in pharyngoesophageal reconstruction.

PMID- 9776195
TI  - Image-guided fine-needle aspiration of the head and neck: five years' experience.
AB  - OBJECTIVE: To evaluate the diagnostic utility of image-guided fine-needle
      aspiration (FNA) in the head and neck. DESIGN: All image-guided FNAs of the head
      and neck performed January 1992 through June 1997 were included. All
      cytohistopathologic data were reviewed and collated. A slide review was performed
      in all cases with cytohistologic discrepancies. SETTING: The Department of
      Radiology, University of Pennsylvania Medical Center, Philadelphia. PATIENTS:
      Patients with deep-seated or poorly localized masses in the head and neck,
      representing both primary or recurrent/metastatic lesions, were referred.
      RESULTS: There were 111 computed tomography-guided FNAs performed in 109
      patients. Sites sampled included parapharyngeal (n = 20), parotid or
      submandibular (n= 25), thyroid (34), and neck, paratracheal/paraesophageal, skull
      base, and paraspinal (n = 32). Diagnostic samples were obtained in 93 cases
      (83.8%). The procedures were well tolerated, without long-term complications.
      Cytologic examination detected a total of 39 malignancies, 24 of which were
      confirmed histologically. Eleven of the remaining malignant FNA cases reflected
      recurrent tumor; there were 3 false-positive FNA cases (2.7%), 2 in the setting
      of previous surgery and/or radiation therapy. There were 2 false-negative
      aspirates from sites deep in the neck (1.8%) among 7 of the 35 patients with
      benign aspirates who underwent surgery. Twenty six patients underwent ultrasound
      guided FNA (thyroid gland only), revealing 1 papillary carcinoma and 1
      intrathyroidal parathyroid gland, both of which were confirmed histologically.
      The findings in the aspirates from the rest of the patients were benign (n = 18),
      Hurthle cell neoplasm (n = 1), and nondiagnostic (n = 5). CONCLUSIONS: (1) The
      cytologic findings were supported clinically and/or histologically in 86 (92%) of
      the 93 diagnostic computed tomography-guided FNA cases. (2) Unnecessary surgery
      was avoided in 37% of the patients with recurrent tumor or benign diagnoses by
      cytologic assessment. (3) Potential pitfalls include false-positive diagnoses
      after radiation therapy and procedural or sampling limitations for deep neck and
      paraspinal lesions.

PMID- 9776197
TI  - Pathologic quiz case 1. Papillary thyroid carcinoma (PTC), combined tall cell and
      columnar variants.

PMID- 9776196
TI  - The subcutaneous pedicle flap in melolabial reconstruction.
AB  - OBJECTIVE: To review and report our experience with the subcutaneous pedicle flap
      in the reconstruction of defects adjacent to the melolabial crease. DESIGN:
      Retrospective review. SETTING: Cutaneous surgery unit of an academic tertiary
      referral center. PATIENTS: One hundred nine patients with defects of the lateral
      aspect of the upper lip, the medial aspect of the cheek, and the melolabial
      crease after Moh excision of cutaneous lesions. CONCLUSIONS: In our experience,
      the subcutaneous pedicle advancement flap is often ideally suited to the
      reconstruction of cutaneous defects adjacent to the melolabial crease. We have
      been particularly satisfied with the results of this reconstructive technique
      when addressing deep defects adjoining the alar facial sulcus in patients with
      full cheeks.

PMID- 9776198
TI  - Pathologic quiz case 2. Liposarcoma of the larynx.

PMID- 9776199
TI  - What role do systemic corticosteroids, immunotherapy, and antifungal drugs play
      in the therapy of allergic fungal rhinosinusitis?

PMID- 9776200
TI  - Allergic fungal rhinosinusitis: experience with immunotherapy.

PMID- 9776201
TI  - Allergic fungal rhinosinusitis: our experience.

PMID- 9776202
TI  - Inner ear pressure in Meniere's disease and fluctuating hearing loss determined
      by tympanic membrane displacement analysis.
AB  - Meniere's disease and fluctuating hearing loss are related to labyrinthine fluid
      pressure variations. The development of a new indirect method of analysis of the
      tympanic membrane displacement during the stapedial reflex, using the Marchbanks
      Measurements System (MMS 10), allows us to study inner ear fluid pressure during
      these pathological conditions. In this study, measurements with this method were
      made in four groups of patients: a control group with normal hearing (n=7),
      stable sensorineural hearing loss (n=9), fluctuating hearing loss (n=8), and
      Meniere's disease (n=25). Results show, first, a good relationship between the
      recording of negative curves, suggesting a high pressure, and the acute episodes
      of fluctuating hearing loss; and, secondly, in the case of Meniere's disease two
      types of situation: positive and negative curves suggesting normal and high
      pressures, respectively.

PMID- 9776203
TI  - Cochlear tuning in the gerbil: a comparison of responses to sinusoidal amplitude
      modulation and difference tone stimuli.
AB  - Vocalizations often have periodic variations of their acoustic waveform envelope.
      Two simultaneously presented frequencies have an envelope fluctuation with a
      frequency equal to their difference tone (DT = F2-F1). Sinusoidal amplitude
      modulation (SAM) of a carrier frequency also produces an envelope fluctuation.
      Electrical ensemble responses to DT and SAM stimuli were recorded from the
      gerbil's round window. The predominant frequency of the response to the DT
      stimuli is F2-F1; to the SAM stimuli, it is the modulation frequency. Both
      responses are spectrally, temporally, and dynamically non-linear. Forward masking
      of a low-frequency DT response produced a tuning curve (TC) with a tip at the
      high-stimulus frequency. Forward masker TCs of a low-frequency SAM ensemble
      response had tips at the high frequency of the carrier. Tip thresholds and
      sharpness of tuning of DT and SAM TCs are quite similar, with cochlear neurons
      having high characteristic frequencies providing sharply tuned information about
      low frequency acoustic envelope periodicities.

PMID- 9776204
TI  - Long-term and short-term variations in amplitude and frequency of spontaneous
      otoacoustic emissions in pre-term infants.
AB  - In pre-term infants, spontaneous otoacoustic emission (SOAE) frequencies show an
      upward shift with time. The present study aimed to monitor the SOAE amplitude
      variation during this frequency shift. A long-term observation of 87 SOAE
      frequencies from 18 pre-term infants yielded a positive frequency shift of 0.72
      per cent per week, which was not accompanied by a simultaneous amplitude shift,
      as the mean variations in SOAE amplitude were practically zero. Furthermore,
      there was no relationship between the short-term SOAE amplitude variation and the
      infant's post-conceptional age. Only the absolute amount of SOAE amplitude
      variation seemed to grow with time. Comparison with induced variations in SOAE
      frequency argues against a middle ear influence on the SOAE frequency shift. In
      our view, the absence of any amplitude shift during the upward SOAE frequency
      shift further suggests cochlear development during the last period of gestation.

PMID- 9776205
TI  - Extended high frequency audiometry in pre-school children.
AB  - Since adequate and reliable earphones are now available and standards have been
      established, clinical audiometry can be performed at extended high frequencies
      (EHFs). In the present study, 47 preschool children (aged 4-7 years) were
      examined with EHFs (8-16 kHz) using the new Sennheiser HDA 200 earphone. The
      hearing thresholds correspond to those of other studies; the median thresholds
      and range increase with increasing frequency. The medians and quartiles were: 10
      kHz: 25 (5-35) dB(SPL), 11.2 kHz: 35 (20-40) dB(SPL), 14 kHz 40 (30-50) dB(SPL)
      and 16 kHz: 50 (40-60) dB(SPL). The hearing thresholds could be more reliably
      determined in the older children (> 5 years) and were 5 dB better than in the
      younger ones (< 5 years). Thresholds in the 10-12.5 kHz range correspond to those
      of adults but are more sensitive by 5-12 dB in the 14-16 kHz range.

PMID- 9776206
TI  - Accuracy of self-reported hearing loss.
AB  - The purpose of this study was to assess the accuracy, in older adults, of
      questions assessing hearing loss. Study participants (n=3,556), aged 48-92 years,
      were examined in a population-based study of age-related hearing loss in Beaver
      Dam, Wisconsin. Self-report data from the ten-question Hearing Handicap Inventory
      for the Elderly-screening Version (HHIE-S), and four additional questions were
      compared with hearing loss as measured by pure-tone air conduction audiometry.
      The single question, 'Do you feel you have a hearing loss?' was the most
      sensitive question (sensitivity=71 per cent); its overall and gender-specific
      prevalence estimates were within 3.2 per cent of prevalence measures derived
      audiometrically, although age-group specific estimates were not as accurate.
      Using an HHIE-S total score >8 resulted in low sensitivity (34 per cent) and
      inaccurate prevalence estimates. These results indicate that, for some
      applications, one simple question may be sufficient for prevalence surveys of
      hearing loss among older adults.

PMID- 9776207
TI  - The self-reported handicapping effect of hearing disabilities.
AB  - This study investigates the extent to which individuals see themselves as being
      handicapped by a hearing disability. Self-reports were obtained with the
      Amsterdam Inventory for Auditory Disability and Handicap which distinguishes five
      basic disabilities: intelligibility in noise, intelligibility in quiet,
      localization of sounds, distinction of sounds and detection of sounds. Responses
      of 239 hearing-impaired people with varying types of hearing loss have been
      examined. The occurrence of the five disabilities in the population as well as
      the self-reported limiting and annoying effect per disability has been examined.
      This study shows that the handicapping effects of the disabilities do not have
      equal weights. Handicap resulting from the inability to understand speech in
      noise is most strongly felt. This paper argues that the type of disability
      jointly determines the severity of a person's handicap.

PMID- 9776208
TI  - Fibrinolysis and the plasma carboxypeptidase.
AB  - Plasma contains the precursor of a carboxypeptidase B-like enzyme. This zymogen
      can be activated by high levels of thrombin, such as those that occur after clot
      formation, or by low levels of thrombin in the presence of thrombomodulin. The
      activated enzyme suppresses fibrinolysis by removing carboxy terminal lysine
      residues from partially degraded fibrin, thereby preventing plasmin-mediated
      positive feedback in the fibrinolytic cascade. The existence of this protein
      implies a direct molecular link between the coagulation and fibrinolytic cascades
      through the thrombin-thrombomodulin complex. This connection most likely plays a
      significant role in maintaining a proper balance between the deposition and
      removal of fibrin.

PMID- 9776209
TI  - The collagen-platelet interaction.
AB  - Collagen-platelet interaction, occurring in hemostasis but also a cause of
      thrombosis, is a two-step process of adhesion and activation involving the
      sequential recognition of distinct receptors. Adhesion involves first the
      reversible recognition of collagen-bound von Willebrand factor by the platelet
      receptor complex Gp Ib/IX/V, followed by direct interaction between collagen and
      the platelet integrin receptor alpha2beta1, which binds to specific sequences in
      collagen in which the GER motif appears important. Platelet activation then
      follows from the recognition by the receptor Gp VI of GPP* sequences in collagen,
      culminating in signalling events unique to collagen as a platelet agonist: Gp VI
      leads via the novel platelet Fc receptor gamma-chain to p72syk and phospholipase
      Cgamma2.

PMID- 9776210
TI  - Problems and prospects in gene therapy for hemophilia.
AB  - The aim of gene therapy for hemophilia is the stable introduction and expression
      of a gene encoding functional blood coagulation factor VIII or IX. Although there
      are as yet no published studies demonstrating long-term expression of therapeutic
      levels in large animal models of the disease, there have been several reports
      over the past year of sustained expression of therapeutic levels of clotting
      factors in small animals, and some of these strategies are currently being
      applied to hemophilic dogs. Recent advances include optimized retroviral gene
      transfer, improved adenoviral vectors for high levels of sustained expression of
      factor VIII in mice, stable therapeutic levels of factor IX expression in mice
      after transduction of muscle or liver with adenoassociated virus vector, as well
      as new nonviral gene delivery strategies. Finally, several important mouse and
      dog models of hemophilia have been characterized during the past year.

PMID- 9776211
TI  - Bleeding and thrombosis in myeloproliferative disorders.
AB  - Patients with polycythemia vera and essential thrombocythemia have a hemostatic
      imbalance, the mechanisms of which are still elusive. Hemorrhagic tendency
      usually manifests in patients with high platelet count and reveals the clinical
      and laboratory features of acquired von Willebrand's disease. In most patients,
      however, the increased risk of arterial and venous thromboses constitutes the
      main therapeutic challenge. Data from large retrospective studies have recently
      allowed us to reassess the clinical epidemiology of these manifestations.
      Erythromelalgia and other peculiar microcirculatory disturbances are selectively
      sensitive to aspirin. This finding, and the thromboxane A2 hyperproduction
      existing in polycythemic and thrombocythemic subjects, provide the rationale for
      the use of low-dose aspirin in these patients. The efficacy and safety of this
      treatment in patients with polycythemia vera is being tested in a large scale,
      randomized trial. Appropriately designed clinical studies are also needed for
      defining the neoplastic risk of commonly used chemotherapic agents and the
      antithrombotic efficacy of alternative cytoreductive strategies.

PMID- 9776212
TI  - Genetic abnormalities in hereditary hemorrhagic telangiectasia.
AB  - Hereditary hemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber disease, is an
      autosomal dominant disorder of localized angiodysplasia, although it is sometimes
      mistakenly identified as a hemostatic disorder due to its associated
      characteristic bleeding. The vascular lesions that develop consist of direct
      arteriovenous connections without an intervening capillary bed. Germline
      mutations in one of two different genes, endoglin or ALK-1, can cause HHT. Both
      are members of the transforming growth factor (TGF)-beta receptor family of
      proteins, and are expressed primarily on the surface of endothelial cells. They
      are associated together in a receptor complex on the cell surface. Biochemical
      studies suggest that endoglin modulates TGF-beta signaling through ALK-1 and the
      type I TGF-beta receptor. Most mutations identified in endoglin and ALK-1 create
      null alleles, which lead to reduced message or protein levels. A model of
      haploinsufficiency is proposed, in which inheritance of a mutation predisposes an
      individual to develop HHT-associated vascular lesions. The factors that initiate
      lesion formation are unknown, but disruption of these genes in mice should
      provide animal models to address these and other important questions about the
      pathogenesis of HHT.

PMID- 9776213
TI  - The prothrombin 20210 G to A variation and thrombosis.
AB  - The 20210 G to A variation in the prothrombin gene was first described in 1996
      and found to be associated with both elevated plasma prothrombin levels and a
      moderately increased risk for first venous thrombotic events. These findings
      generally have been confirmed in several independent studies. The 20210A allele
      seems to be rather common in white subpopulations, among whom the prevalence of
      heterozygous carriers may vary from 1% to 5%. The variant prothrombin allele
      contributes to the risk of thrombosis in carriers of other genetic risk factors
      (eg, factor V Leiden); also, this allele seems not to be an important risk factor
      for arterial thrombosis, unless risk factors for cardiovascular disease (eg,
      smoking) also are present.

PMID- 9776214
TI  - Mechanisms of thrombosis in hyperhomocysteinemia.
AB  - Hyperhomocysteinemia is now recognized as a common risk factor for thrombotic
      vascular events such as stroke, myocardial infarction, and venous thrombosis.
      Studies of cultured cells in vitro indicate that homocysteine has prothrombotic
      effects on the endothelium and vascular smooth muscle. An association between
      moderate hyperhomocysteinemia and vascular dysfunction was confirmed in recent
      studies in animals and humans. Current models propose that dysregulation of
      homocysteine metabolism may impair vascular function through mechanisms involving
      oxidant stress or altered cellular methylation. Although moderate
      hyperhomocysteinemia can be treated effectively by administration of folic acid
      and other B vitamins, the clinical benefit of this therapeutic approach has not
      been proven in patients with thrombosis.

PMID- 9776215
TI  - Oral contraceptives and thrombosis.
AB  - The debate on whether the so-called third-generation progestogens (desogestrel,
      gestodene, and norgestimate) are associated with a higher risk of venous
      thrombosis than the older, so-called second-generation progestogens (principally
      levonorgestrel and norethindrone) continues. Much of the debate focuses on
      finding alternative explanations for the observed relationship. Alternative
      explanations include a prescribing bias, in which women at greater risk of venous
      thromboembolism were preferentially prescribed newer preparations; a failure by
      researchers to adjust adequately for residual confounding by age; and a failure
      by researchers to allow adequately for confounding by the duration of use of oral
      contraceptives. None of these explanations have been accepted without dispute,
      and the debate will clearly continue. A possible biologic explanation for the
      observed relationship of higher thrombosis risk with use of third-generation
      preparations has been put forward by Rosing et al. from Maastricht, who developed
      a new way of measuring activated protein C (APC) resistance. They found that
      users of third-generation preparations have higher acquired APC resistance than
      users of second-generation products. This finding requires confirmation.

PMID- 9776216
TI  - Prevention and management of central venous catheter thrombosis.
AB  - Central venous catheters play an integral part in the treatment of patients with
      a variety of illnesses. Complications, although not common, do occur. However,
      the benefits of these devices far outweigh the risks. Thrombosis, one of the most
      common problems, can be divided into three distinct clinical entities. The
      prophylaxis, diagnosis, pathogenesis, and treatment of central venus catheter
      related thromboses are critical in the treatment of patients requiring long-term
      venous access.

PMID- 9776218
TI  - Bibliography. Current world literature. Hemostasis and thrombosis.

PMID- 9776217
TI  - Recent clinical trials in the treatment of venous thromboembolism and unstable
      angina with low molecular weight heparins.
AB  - Low molecular weight heparins (LMWHs) have a more predictable anticoagulant
      response, better bioavailability when administered by subcutaneous injection, and
      a longer plasma half-life than unfractionated heparin. Consequently, LMWHs can be
      administered by subcutaneous injection, once daily, without laboratory
      monitoring. When used in this way, LMWHS are as safe and effective as
      unfractionated heparin administered by continuous intravenous infusion with
      laboratory monitoring for the treatment of venous thrombosis and pulmonary
      embolism, and at least as safe and effective as unfractionated heparin for the
      treatment of unstable angina. Three recent studies demonstrated that because of
      their improved pharmacokinetic properties, LMWHs can be used to treat selected
      patients with venous thrombosis in the out-of-hospital setting.

PMID- 9776220
TI  - SV40 infections in simians and humans.

PMID- 9776219
TI  - Introduction to simian virus 40: getting by with more than a little help from its
      host cell.
AB  - More than three decades of research on simian vacuolating virus 40 (SV40) have
      generated a richly detailed picture of the viral genome, the events in infection,
      and the functions of the viral proteins in the host cell. This contribution
      briefly reviews our current understanding of SV40 biology as an introduction to
      this symposium volume on its role as a possible human polyoma-virus.

PMID- 9776221
TI  - Simian virus 40 DNA sequences in human brain and bone tumours.
AB  - This report reviews recent observations regarding the association of simian virus
      40 (SV40) DNA sequences with brain and bone tumours of childhood [1-3]. Our
      initial investigation was suggested by the tumorigenicity of SV40 in animals, and
      the transgenic mouse expression of SV40 large T-antigen in which all animals
      developed choroid plexus (CP) tumours. Polymerase chain reaction (PCR) analysis
      and DNA sequencing demonstrated SV40-like DNA sequences, amplified from the "Rb
      pocket" binding domain of the viral large T-antigen, in 10/20 CP and 10/11
      ependymoma tumours of children. The PCR analysis was subsequently extended to
      three additional regions of the viral genome: the carboxy-terminal region of
      large T-antigen, the viral enhancer/origin, and the VP1 gene. All amplified
      products were related to SV40 sequences. Furthermore, because one individual in
      the original brain tumour study was a member of a Li-Fraumeni kindred, 151 DNA
      samples from such families were analysed. Only 18 were positive for viral
      sequences and 11 of these were isolated from individuals with osteosarcomas. This
      observation led to a further analysis of DNA from bone tumours, in which 54/160
      samples contained SV40-like sequences. These studies associate SV40-like
      sequences with human CP, ependymoma, and bone tumours. A causal relationship to
      human oncogenesis remains a subject for further study.

PMID- 9776222
TI  - Detection of authentic SV40 DNA sequences in human brain and bone tumours.
AB  - This report summarizes our follow-up studies of SV40 DNA sequences in human brain
      tumors of early childhood and our confirmation of the presence of SV40 DNA in
      human osteosarcomas. We examined brain tumors and osteosarcoma samples by the
      polymerase chain reaction (PCR) using primers from four separated regions of the
      SV40 genome. Sequence analysis confirmed that authentic SV40 DNA was present. The
      regulatory region of each tumor-associated viral DNA was of archetypal length
      (non-duplicated enhancer); sequence variation was noted at the extreme C-terminus
      of the large T-antigen (T-ag) genes. Infectious SV40 was recovered from one brain
      tumor. We sequenced the entire early genomic region from three human isolates of
      SV40 and two laboratory strains originally recovered from monkeys. The predicted
      amino acid sequence of the large T-ags showed remarkable sequence conservation
      among isolates, except for a small variable region identified at the C-terminus
      of the protein. There were no human-isolate-specific changes detected that could
      serve to distinguish a human variant of SV40 nor were any tumor-type-specific
      viral markers observed. Based on these data, we conclude that authentic SV40 is
      associated with some human brain and bone tumors and that multiple SV40 strains
      can infect humans.

PMID- 9776224
TI  - SV40 DNA sequences in mesotheliomas.
AB  - To investigate the presence of SV40 DNA sequences in human British mesotheliomas,
      PCR analysis using PYV and SV primers which amplify a 172 bp fragment of SV40LTAg
      and a 105 bp fragment unique to the SV40LTAg respectively was performed on
      archival and frozen tissues. Nine pleural mesotheliomas, nine adenocarcinomas
      metastatic to the pleura and three inflammatory disorders of the pleura were
      studied. PCR positivity with the SV primer set was restricted to four of the nine
      cases of mesothelioma with concordance between paraffin embedded and frozen
      tissues. Positivity with the PYV primer set was observed in six mesotheliomas,
      two adenocarcinomas and one of the reactive pleurae. This study indicates that
      SV40 DNA sequences are present in a substantial proportion of British
      mesotheliomas.

PMID- 9776223
TI  - Evidence for and implications of SV40-like sequences in human mesotheliomas and
      osteosarcomas.
AB  - Pleural mesotheliomas and osteosarcomas develop in hamsters injected
      intracardially with SV40. Using primers specific for the RB-pocket binding domain
      of SV40 we analysed with the polymerase chain reaction frozen specimens from 48
      human mesotheliomas and 145 human bone tumours. We found that 60% of human
      mesotheliomas and 33% of human bone tumours contained SV40-like DNA.
      Immunostaining, Western blot and RNA in situ hybridization experiments revealed
      SV40 Tag expression in human mesotheliomas. Osteosarcomas were not studied for
      Tag expression because not enough material was available. Finally, antibodies
      anti-Tag were detected in the sera collected from patients with mesothelioma.
      These data indicate that SV40, or a closely related virus, is/are present in
      human mesothelioma and osteosarcoma.

PMID- 9776225
TI  - Simian virus 40-like DNA sequences and large-T antigen-retinoblastoma family
      protein pRb2/p130 interaction in human mesothelioma.
AB  - The oncoprotein of the Simian virus 40, SV40 large T-antigen (Tag), is reported
      to target and inactivate growth-suppressive proteins such as the retinoblastoma
      (Rb) family and p53 leading to transformation of human cell lines in vitro, to
      produce tumours in rodents, and to be detected in several human cancers including
      mesothelioma. In support of the potential role of SV40 Tag in the pathogenesis of
      certain human cancers, we have found SV40-like sequences in 8/25 bioptic
      specimens of mesothelioma from patients with exposure to asbestos fibres. We have
      also demonstrated that the SV40 Tag detected in human mesothelioma binds the
      retinoblastoma family protein pRb2/p130 in 5/5 specimens studied. We submit that
      the tumorigenic potential of SV40 Tag in some human mesotheliomas may arise from
      its ability to interact with and thereby inactivate several tumour and/or growth
      suppressive proteins in cooperation with asbestos fibres in inducing pleural
      mesothelioma.

PMID- 9776226
TI  - Simian virus 40 footprints in normal human tissues, brain and bone tumours of
      different histotypes.
AB  - SV40 footprints were investigated by PCR in normal human tissues and tumours of
      different histotypes, followed by Southern blot hybridization with a specific
      internal oligoprobe for SV40 DNA. Specific SV40 amplification products were
      detected at high prevalence in primary human brain tumours: 83% of choroid plexus
      papillomas, 75% ependymomas, 47% astrocytomas and 37% glioblastomas. SV40
      footprints were also revealed in primary bone tumours: 35% osteosarcomas and
      Ewing's tumours. Positive normal tissue samples ranged from 45% of sperm fluids
      to 8% of brain tissue. Normal bone tissue specimens were SV40 negative. These
      results indicate that SV40 is associated with human brain and bone neoplasms,
      whereas normal bone and brain tissues were either SV40 negative or positive at
      low grade. SV40 footprints were found in other normal samples such as PBC, B- and
      T-lymphocytes and sperm fluids, indicating that SV40 is latent in these cells.
      Therefore, these cells may be vectors of SV40 in other host tissues and may
      spread SV40 infection by blood transfusion and sexual transmission in the human
      population.

PMID- 9776227
TI  - Search for SV40 in human mesotheliomas.

PMID- 9776228
TI  - Molecular biology and pathogenesis of human polyomavirus infections.
AB  - The two human polyomaviruses JC and BK are ubiquitous in the human population.
      Primary infection leads to lifelong persistence in the kidney, the CNS and in
      lymphoid cells. Virus is shed into the urine and is transmitted at least in part
      by the oral route. Under limited changes of the immunological state persistent
      polyomavirus infection is activated to an asymptomatic virus production. However,
      in severe long-lasting immunosuppression, highly effective virus multiplication
      can be accompanied by extended cytolytic damage of viral target cells leading to
      fatal disease. Whereas BKV is associated with severe urogenital disorders, JCV
      affects the CNS, leading to progressive multifocal leukoencephalopathy (PML).
      Although the number of PML cases is steadily increasing because of the AIDS
      epidemic, the mechanisms responsible for the change from asymptomatic-activated
      to the diseased state are not yet understood. As a possible pathogenic factor,
      the role of genomic heterogeneity of the transcriptional control region in the
      induction of disease is discussed.

PMID- 9776229
TI  - BK virus as a potential co-factor in human cancer.
AB  - BK virus (BKV) is a member of the polyomavirus family that persistently infects
      75-80% of the human population. BKV encodes a large T antigen which is
      responsible for the transforming functions of the virus. Recent studies have
      shown an association of BKV DNA with a variety of human tumours including
      pancreatic islet, brain, urinary tract and Kaposi's sarcoma. Despite the
      detection of BKV DNA in several human tumours, there is no clear evidence for a
      causative role in tumour formation. We have sought to characterize the
      interactions of BKV TAg with cellular tumour suppressor proteins including p53,
      pRb, p107, and p130 in an attempt to further understand the molecular mechanisms
      of transformation by BKV. We have shown that BKV TAg can bind to and functionally
      inhibit p53 and the p53-mediated response to DNA damage. Additionally, we have
      shown that low levels of BKV TAg are sufficient to induce free E2F and a serum
      independent phenotype despite the absence of detectable interactions with pRb
      family members. Taken together, these results suggest that BKV TAg can both
      inhibit the cellular response to DNA damage and induce proliferation, allowing
      for potential accumulation of mutations in cellular growth control genes. These
      results suggest a possible role for BKV TAg in cellular transformation and tumour
      formation in the human host.

PMID- 9776230
TI  - Oncogenic potential of human neurotropic papovavirus, JCV, in CNS.
AB  - The human polyomavirus, JCV, is the causative agent of Progressive Multifocal
      Leukoencephalopathy (PML), a fatal human demyelinating disease. PML results from
      the cytolytic destruction of oligodendrocytes, the myelin-producing cells of the
      nervous system. JCV has also been shown to be tumorigenic in several animal
      models. Transgenic mice expressing the JCV early protein, T-antigen, develop
      poorly differentiated neural crest origin tumours. Intracerebral inoculation of
      JCV into newborn hamsters induces medulloblastomas, astrocytomas, and primitive
      neuroectodermal tumours. Further, inoculation of the virus into the brains of non
      human primates, owl and squirrel monkeys, results in astrocytomas and
      glioblastoma multiforme. Several case reports have associated JCV with human CNS
      tumours in patients with concomitant PML, and one such report has detected JCV in
      a glial tumour in the absence of PML. The induction of neural origin tumours by
      JCV has been studied in transgenic mice harbouring the early genome of the virus.
      Alterations in the level and function of tumour suppressor proteins p53 and Rb,
      as well as associated cell cycle regulators, have been detected in tumour tissue
      from JCV T-antigen transgenic mice. Possible mechanisms by which JCV may exert
      its oncogenic potential by alteration of cellular growth control pathways in both
      humans and experimental animals are discussed.

PMID- 9776231
TI  - Rearranged and chimaeric primate polyomavirus genomes.
AB  - Recombination between different primate polyomavirus genomes (SV40, JCV, BKV) or
      within the genome of the same species (e.g. archetype to rearranged type virus)
      might contribute to the establishment of SV40-like viruses within the human
      population. Alternatively, it is possible that these polyomaviruses might, upon
      co-infection of human cells, complement each other's growth through direct virus
      virus interactions or by indirect effects on host cell permissiveness. Our
      laboratory has investigated the activity of JCV-BKV-SV40 chimaeras constructed in
      vitro, and some of them exhibit altered lytic, host range, and oncogenic
      behaviour. Our work has also included the PCR analysis of human tissue specimens
      for the presence of polyomaviral sequences. Archetype and rearranged variants of
      JC virus have been detected in normal and diseased tissues, but evidence for
      naturally arising JCV-BKV or JCV-SV40 recombinant genomes has not been obtained.

PMID- 9776232
TI  - JC virus infection in cells from lymphoid tissue.
AB  - Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease
      characterized by infection of oligodendrocytes by JC virus. The exact nature of
      the pathogenesis of PML is not known. The nature of the primary infection, the
      site of viral latency, and the route by which JCV enters the brain remain to be
      elucidated. Different laboratories have shown the presence of JCV in peripheral
      lymphocytes from immunosuppressed individuals, suggesting these cells as possible
      carriers of JCV to the brain. To examine this observation, we tested the
      susceptibility to JCV infection of cells from lymphoid organs, focusing our
      attention on CD34+ haematopoietic precursor cells and B lymphocytes. The results
      demonstrate that both these cell types are susceptible to JCV infection and,
      moreover, that JCV can infect only those cells that differentiate into
      lymphocytic lineage.

PMID- 9776233
TI  - Detection of SV40 sequences in human mesothelioma.
AB  - The presence of SV40 DNA sequences in British cases of mesothelioma was
      investigated using previously reported PCR assays. Three different SV40 primer
      sets were used which gave positive detection rates of 100% (SV.for3/SV.rev), 42%
      (PYV.for/rev) and 15% (SV.for2/SV.rev). When 26 mesothelioma biopsies were
      tested. Negative samples included 22 semen samples from AIDS patients, 10 blood
      donor DNAs and the human mesothelioma cell line H-MESO-1. The problems
      encountered with these assays and the interpretation of the results are
      discussed.

PMID- 9776234
TI  - A broad spectrum PCR method for the detection of polyomaviruses and avoidance of
      contamination by cloning vectors.
AB  - Polyomaviruses induce tumours of different histological types when inoculated
      into experimental animals, but their aetiological role in the development of
      malignant tumours in humans remains questionable. We developed a degenerate PCR
      assay in an attempt to identify additional, presently unknown human polyomavirus
      types which may be involved in the malignant transformation of human tissues.
      Degenerate oligonucleotide primers were deduced from four different conserved
      amino acid motifs in the highly conserved viral capsid protein, VP1. Three
      different sets of primers were included for the each test. Bladder carcinomas,
      Hodgkin's lymphomas, meningiomas, Kaposi-tumours and -cell lines were analysed.
      No polyomavirus DNA sequences could be detected. A comparative analysis led to
      the recognition of the presence of SV40 DNA sequences in more than 200 vectors
      available in the EMBL and Genbank Databanks and commonly used in laboratories
      worldwide. The majority of primers used to detect polyomavirus sequences in human
      tumours are distributed throughout these regions also present in the vectors.
      Only a small stretch of 286bp in the overlapping region of the VP1, VP2 and VP3
      genes is not present in the vector sequences. We propose to use this region for
      the design of additional non-contamination primers.

PMID- 9776235
TI  - Further validation of SV40-like DNA in human pleural mesotheliomas.
AB  - We have confirmed in a second set of patients having human pleural mesothelioma
      that DNA for regions of the amino terminus of SV40 Tag can be amplified by the
      polymerase chain reaction. Moreover, other regions, including the carboxy
      terminus for Tag, and the regulatory region of SV40, are present in these
      specimens.

PMID- 9776236
TI  - Detection of SV40-like DNA sequences in pleural mesothelioma, bronchopulmonary
      carcinoma and other pulmonary diseases.
AB  - Mesotheliomas are pleural-based tumours mainly associated with asbestos exposure
      (70% of cases) and the incidence is still raising. Recently, a possible viral
      connection was reported and 60% of mesotheliomas were demonstrated to contain and
      express SV40-like DNA sequences. In this study, the presence of SV40-like DNA
      sequences were investigated in mesotheliomas (15 tissue samples and six cell
      lines) and in 63 additional bronchopulmonary carcinomas, one parietal
      osteosarcoma and non-malignant lung samples as well as in organizing pleuritis
      (8). Finally, 163 samples were analysed by the polymerase chain reaction (PCR)
      with a set of primers PYV.for and PYV.rev to amplify a 173 bp region of the SV40
      Tag. and a 179 bp region JC virus (JCV) as well as a 182 bp region BK virus
      (BKV). PCR amplification and hybridization with a probe specific for SV40 Tag
      revealed that 47.6% of mesotheliomas, 28.6% of primary bronchopulmonary
      carcinomas and 16% of non-neoplasic lung diseases contained SV40-like DNA
      sequences. No statistically significant difference in the occurrence of these DNA
      sequences was found between malignant mesothelioma and bronchopulmonary
      carcinoma. However, a significantly higher number of mesothelioma cases exhibited
      SV40- like DNA sequences in comparison with non-malignant pleural and pulmonary
      tissues. The DNA sequences were not related to BK and JC virus sequences. These
      results indicate that SV40-like DNA sequences are present in mesotheliomas as
      well as in bronchopulmonary carcinomas and non-malignant pleuropulmonary
      diseases.

PMID- 9776237
TI  - BK virus in brain tumours.

PMID- 9776238
TI  - Consideration of PCR methods for the detection of SV40 in tissue and DNA
      specimens.
AB  - SV40 is capable of infecting humans, although its association with human diseases
      remains controversial. Recently, a subgenomic SV40 DNA sequence was detected by
      polymerase chain reaction (PCR) in certain types of human tumour tissue as well
      as in normal pituitary tissue. However, due to the limited DNA sequence
      information that was obtained in those experiments, SV40 could not be
      authenticated, and it was uncertain whether a related or hybrid virus (or
      endogenous DNA) accounted for the PCR-amplified DNA. To gain more insight into
      these observations, we are experimenting with PCR primers directed at various
      sites of the SV40 genome, as well as with various parameters of the PCR assay. In
      this communication, we describe methodology we currently use in our studies and
      discuss problems associated with the PCR detection of SV40 in various types of
      samples.

PMID- 9776239
TI  - Discovery of simian virus 40 (SV40) and its relationship to poliomyelitis virus
      vaccines.
AB  - Simian Virus 40 (SV40) was discovered in 1959 as a covert contaminant of
      poliovirus vaccines prepared using Macacus monkey renal cell cultures. This
      inapparent polyoma virus of monkeys was detected using Cercopithecus renal cell
      cultures and was eliminated from poliovaccines. There has been no evidence to
      implicate SV40 virus of vaccine origin in long- or short-term consequences in
      human subjects. Of importance, SV40 virus provided a new model for basic studies
      of viral pathogenesis and for cell transformation and neoplasia. Neoplastic
      transformation is fixed on the promiscuous binding of SV40 large T antigen to
      anti-oncogene cellular protein elements. SV40 also served as a valuable model for
      defining the immunology of virus-induced cancer and in its prevention and cure.
      Further, it has been a prime tool for elucidating the molecular details of
      eukaryotic cell processes. Numerous techniques now used in molecular biology were
      pioneered in the SV40 system. The SV40 promoter is commonly used in vector
      expression constructs and it has continued to be a model to develop new tools for
      site-specific mutagenesis. The virus has been critically important to studies in
      modern genetics and in molecular biology.

PMID- 9776240
TI  - Host range analysis of simian virus 40, BK virus and chimaeric SV40/BKV: relative
      expression of large T-antigen and Vp1 in infected and transformed cells.
AB  - Simian virus 40 (SV40) persists in Rhesus monkeys and productively infects
      cultured simian kidney cells. In contrast to the closely related human virus BKV,
      SV40 is known to propagate inefficiently in human embryonic kidney (HEK) cells
      and human fibroblasts (HFF). We examined the growth of SV40, BKV and the
      chimaeric genome virus, SV40/RFV, in several types of human cells. We analysed
      replication, expression of T-Ag and Vp1 capsid proteins, and cytopathic effects
      (CPE). We also compared T-Ag and Vp1 expression in infected versus transformed
      HFF cells. Although SV40 DNA replicated in HFF and in one subtype of HEK cells,
      viral DNA accumulated slowly and did not reach high levels until six to eight
      weeks after transfection. In HFF or HEK cells there was little T-Ag produced but
      Vp1 was produced in significant amounts in HFF cells. In HFF cells the Vp1/T-Ag
      ratio was approximately 200: 1, and expression of the viral late region appeared
      to inhibit expression of the T-Ag gene. In contrast, BKV and the SV40/RFV hybrid
      propagated well in HEK and HFF cells. The Vp1/T-Ag ratios were also high in BKV
      and SV40/RFV infected HFF cells but more T-Ag was produced with BKV and SV40/RFV
      Because SV40/RFV contained the RFV capsid genes but a SV40 T-Ag gene and
      regulatory region, the human versus simian host range of SV40 was controlled by
      the viral late region, or one or more capsid proteins. This suggested that the
      production of small amounts of T-Ag could not by itself account for poor growth
      of SV40 in HFF cells and that very small, barely detectable amounts of T-Ag were
      sufficient to activate Vp1 gene expression. Also, although some feature of the
      SV40 late region prevented rapid growth of the virus in HFF cells, poor virus
      growth could not be explained by the inability to produce a significant amount of
      Vp1. Although little T-Ag accumulated in SV40 infected HFF and HEK cells,
      transformants contained large amounts of T-Ag. In transformants there was a
      reversal of the Vp1/T-Ag ratio, such that T-Ag was now in 10-20 fold greater
      amount than Vp1. The relatively large amount of T-Ag in transformants could be
      accounted for by the relative absence of Vp1, which may inhibit T-Ag production,
      or by integration of the T-Ag gene at a site in the cell DNA which allows for
      elevated T-Ag gene expression.

PMID- 9776241
TI  - SV40 in adenovirus vaccines and adenovirus-SV40 recombinants.
AB  - During the development of adenovirus (Ad) vaccines in the 1950s, Ad strains 1-5
      and 7 recombined with SV40 during adaptation to growth in rhesus monkey kidney
      cells. The recombination events between the Ad and SV40 genomes produced hybrid
      viruses that contained, within the Ad genome, either portions of the early region
      of the SV40 genome or single or multiple copies of the entire SV40 genome
      inserted in a configuration that permitted the generation of SV40 progeny. When
      portions of the SV40 early region were inserted into the Ad2 E3 region, a region
      non-essential for viral replication, the resulting Ad-SV40 hybrids were non
      defective in that they were capable of independent replication. Such hybrids have
      no known selective advantage for replication in human tissues; however, through
      inadvertent human exposure it is theoretically possibly that they could be
      induced to spread in the environment. Because of deletions in the Ad genome, the
      Ad-SV40 hybrids that contain infectious SV40 DNA were defective and were not
      capable of replication without a helper virus. Due to the low frequency with
      which cells in an infected individual could be co-infected with both defective
      hybrid and helper virions, it is unlikely that such defective viruses could be
      established in the population. Based on the Ad-SV40 model, it is theoretically
      possible that SV40 could recombine with other DNA viruses that infect humans. The
      introduction of Ad-SV40 hybrids or SV40-other virus hybrids into the environment
      could contribute to establishing SV40 as a human polyomavirus and to the SV40 DNA
      sequences that are being detected in human tissues.

PMID- 9776242
TI  - Product quality control testing for the oral polio vaccine.
AB  - A brief overview regarding the quality control testing of the Sabin oral polio
      vaccine is provided. Product testing procedures and specifications are
      established through product license agreements between the vaccine manufacturer
      and the FDA Center for Biologics Evaluation and Research. The manufacture and
      testing of ORIMUNE is a multi-stage process that is closely monitored by the FDA
      following explicit protocols and requires extensive quality control testing at
      various stages.

PMID- 9776243
TI  - Examination of poliovaccines for the presence of SV40 sequences.
AB  - Batches of monovalent oral poliovirus vaccine bulks previously screened for
      infectious SV40 by cell culture methods and used in the United Kingdom from 1971
      96 in trivalent oral poliovirus vaccine have now been examined by a newly
      developed PCR for the presence of SV40 sequences. Up to April 1997, over 190
      batches have been examined. SV40 sequences were not detected in any of the
      vaccines. This provides additional assurance that oral poliovirus vaccines used
      in the U.K. from 1971 are free of SV40 contamination.

PMID- 9776244
TI  - Potential exposure to SV40 in polio vaccines used in Sweden during 1957: no
      impact on cancer incidence rates 1960 to 1993.
AB  - U.S. polio vaccines produced during the 1950s were potentially contaminated by
      simian virus 40 (SV40). Recently DNA from SV40 has been detected in brain
      ependymoma, pleural mesothelioma and osteosarcoma. In 1957, when national polio
      vaccination was started in Sweden, vaccine potentially contaminated with SV40 was
      given to approximately 700,000 individuals, mainly pre-school and school children
      born between 1946 and 1953. From 1958, a Swedish inactivated polio vaccine was
      exclusively used, which has been claimed to be free of SV40. We explored cancer
      incidence rates in the cohorts exposed to the potentially contaminated polio
      vaccines in Sweden. The Swedish Cancer Registry provided annual cancer incidence
      rates in five-year age groups for the years 1960-93. Cancer incidence in cohorts
      maximally exposed was followed during this period, and the incidence when these
      cohorts reached a specific age was compared to the incidence when unexposed
      cohorts reached the same age. For osteosarcoma and brain ependymoma overall age
      standardised incidence rates were essentially unchanged between 1960 and 1993,
      and age specific rates were similar in the exposed and unexposed male and female
      cohorts. During the same period, overall age standardised incidence rates in
      males of brain cancers increased from 9.0 to 13.1 and of pleural mesotheliomas
      from 0.2 to 2.1 per 100,000. None of these increased rates was associated with
      the exposed cohorts. The use of potentially SV40 contaminated inactivated polio
      vaccines in Sweden has not been shown to be associated with increased cancer
      incidence. However, the exposed cohorts have not yet reached the age of increased
      risk of brain cancer or mesothelioma.

PMID- 9776245
TI  - Exposure to SV40-contaminated poliovirus vaccine and the risk of cancer--a review
      of the epidemiological evidence.

PMID- 9776246
TI  - SV40 as a putative human commensal.

PMID- 9776247
TI  - Simian virus 40 oncogenesis in hamsters.
AB  - Simian virus 40 (SV40) is a DNA tumour virus which is highly oncogenic in
      hamsters. Only specific histologic types of tumours develop in hamsters injected
      with SV40, and these are influenced by the route of virus inoculation. When SV40
      is injected systemically to expose most different cell types to the virus, the
      animals develop mesotheliomas, osteosarcomas, sarcomas, and lymphomas within six
      months. When the virus is injected subcutaneously, sarcomas at the site of
      injection develop. If hamsters are injected intracranially with SV40, they
      develop ependymomas. These same tumour types have been found to contain SV40.

PMID- 9776248
TI  - SV40 rodent tumour models as paradigms of human disease: transgenic mouse models.
AB  - Transgenic mice have been used to study the process of Simian Virus 40 (SV40)
      induced oncogenesis in a broad range of tissues including mammary gland, salivary
      gland, pancreas, prostate, liver, lung, kidney, intestine, brain, choroid plexus,
      lens of the eye, bone, smooth muscle and cartilage. The focus of these studies
      rests primarily on the action of the major transforming viral oncoprotein, the
      large T antigen (TAg). In most transgenic studies, the DNA coding sequence of the
      SV40 TAg is placed under the control of a tissue specific promoter which is
      responsible for directing TAg expression to the selected organ. This review
      focuses on the process of viral oncogenesis in the mammary and salivary glands.
      The role of TAg in the induction of apoptosis in the mammary gland, and the time
      dependency of TAg induced hyperplastic changes in the salivary gland, are
      emphasized.

PMID- 9776250
TI  - SV40-mediated transformation and immortalization of human cells.
AB  - SV40 infection of human cells results in both transformation and lytic infection.
      We have used origin-defective viral mutants which are unable to replicate in
      permissive cells to help analysis of transformation. Expression of large T
      antigen (T ag) and small t antigen results in the altered growth phenotypes
      characteristic of transformation in other species. Human diploid fibroblasts (HF)
      have a limited lifespan and undergo senescence; T ag results in extension of
      lifespan but only in rare cases are the cells capable of continuous growth and
      are immortal. We have developed matched sets of non-immortal and immortal
      transformed HF for assessment of the steps required for immortalization. Results
      are summarized to characterize both T-dependent and T-independent functions. A
      novel growth suppressor gene SEN6 has been identified, the inactivation of which
      is required for immortalization; it may also serve as a marker to distinguish
      cells in which SV40 is replicating from those in which it is responsible for
      tumorigenesis.

PMID- 9776249
TI  - Small-t and large-T antigens cooperate to drive cell proliferation.
AB  - Optimal transformation efficiencies or tumour formation in certain target tissues
      require the SV40 small-t antigen in addition to the transforming protein, large
      T. We have used two model systems in which small-t is required for transformation
      to roles of individual viral proteins in this process. These systems include
      anchorage-independent growth of rat fibroblasts and focus formation by primary
      human diploid fibroblasts. In both cases, large-T and small-t antigens work
      together to drive cell cycle induction. Thus, the need for both tumour antigens
      is apparent in the initial step of the transformation process, the stimulation of
      quiescent cells to enter the cell cycle.

PMID- 9776251
TI  - Experimental tumour induction by SV40 transformed cells.
AB  - Although SV40 transforms cells from many species, transformed cells from species
      other than the Syrian hamster are rarely tumorigenic in immunocompetent animals.
      However, secondary manipulations of SV40-transformed cells can result in
      increased tumorigenicity. Some early observations on tumour induction by SV40 and
      transformed cells will be followed by a selected review of evidence suggesting
      that tumorigenicity of SV40-transformed cells involves serial mutations. An SV40
      transformed rat cell model will be described to illustrate the changes in
      tumorigenic phenotype that can occur during tumour progression. This information
      will be used to propose that SV40 immortalization of cells (other than hamster
      cells) is only the first in a series of steps in the pathway toward
      tumorigenicity and that a complete understanding of the oncogenicity of SV40 will
      require definition of the secondary genetic events which complement SV40
      immortalization to create the fully tumorigenic phenotype.

PMID- 9776252
TI  - Molecular chaperone function of the SV40 large T antigen.
AB  - The SV40 large T antigen (T antigen) is a potent viral oncogene capable of
      inducing tumours in test animals and transforming cells in culture. T antigen
      possesses multiple transforming functions that act in a cell-type dependent
      manner. One of these transforming functions requires a physical association
      between T antigen and the cellular tumour suppressor p53, while another requires
      T antigen binding to the retinoblastoma family of tumour suppressors. A third
      transforming function, <<Activity X>>, maps to the amino terminus of large T
      antigen, sequences also present in small t antigen. Our recent studies have shown
      that Activity X: (i) is a J-domain and that T antigen possesses the biochemical
      properties of a DnaJ molecular chaperone; (ii) must act in cis with the T antigen
      Rb-family binding motif to transform; and, (iii) must act in cis with some factor
      through its carboxy terminal half of T antigen, possibly p53, to transform.

PMID- 9776253
TI  - The effect of an antisense expression plasmid to the IGF-1 receptor on hamster
      mesothelioma proliferation.
AB  - We have evaluated the effect of antisense IGF receptor transcripts on the
      proliferation and tumorigenicity in an SV40-induced, immunocompetent hamster
      mesothelioma model (H9A). Expression of IGF-1 and IGF-1 receptor (IGF-1 R) genes
      was identified from H9A RNA using RT-PCR and Northern blot analysis. H9A cells
      were electroporated with inducible expression vectors (under the transcriptional
      control of heat shock promotor HSP70) containing a cDNA fragment corresponding to
      bp 1-309 of IGF-1 R in the sense or antisense orientation to generate the
      respective clones A3 sense or B9 antisense. At 39 degrees C, the B9 antisense
      transfectants demonstrated significantly less proliferation than A3 sense
      transfectants (p2 < 0.02). At 34 degrees C, cell growth of A3 sense and B9
      antisense transfected cells was not significantly different. The A3 sense clones
      resulted in greater numbers of tumours in vivo compared to the B9 antisense clone
      (p2 = 0.0001). The inhibitory effect of IGF-1R antisense transcripts on hamster
      mesothelioma demonstrated in this study by decreased growth and tumorigenicity in
      vitro and in vivo may have implications for the therapy of human mesothelioma.

PMID- 9776254
TI  - Cytotoxic T lymphocyte recognition sequences as markers for distinguishing among
      tumour antigens encoded by SV40, BKV and JCV.
AB  - Simian virus 40 (SV40) has been shown to be associated with a number of human
      tumours. Two other human papova viruses, BKV and JCV, infect humans at a
      relatively high frequency and are activated upon immune suppression. The T
      antigens of both of these viruses share considerable homologies with the
      transforming protein T antigen of SV40. We have used SV40 T antigen specific
      cytotoxic T lymphocyte (CTL) clones to discriminate among the T antigens of SV40,
      BKV and JCV. These CTL clones directed to four distinct CTL epitopes serve as
      specific probes and can differentiate subtle alterations or deletions in the CTL
      epitopes relative to SV40 T antigen. Using this strategy, we have been able to
      authenticate three SV40 viruses isolated from humans as all four distinct CTL
      epitopes in the T antigens encoded by these three SV40 human isolates (SVCPC,
      SVMEN, and SVPML-1) were found to be identical to prototype SV40. We have further
      identified a 198 amino acid deletion T antigen variant of SVCPC. The finding of a
      deletion mutant in the SVCPC virus population suggests that the cellular immune
      response may play a role in the selection of antigenic loss variants.

PMID- 9776255
TI  - Immunotherapy of SV40 induced tumours in mice: a model for vaccine development.
AB  - Various vaccination strategies were compared for their ability to elicit antigen
      specific tumour immunity, using the SV40-BALB/c murine tumour system.
      Specifically, mice were injected with baculovirus-derived recombinant SV40 Tag
      (rTag), synthetic peptides corresponding to B cell epitopes on SV40 Tag or a
      plasmid DNA construct encoding the gene for SV40 Tag. In vivo tumour immunity was
      determined by a lethal tumour challenge with syngeneic SV40-transformed tumour
      cells. SV40 Tag-specific antibody titres were induced in mice immunized with rTag
      or Tag synthetic peptides. Partial tumour protection was observed in mice that
      were immunized with SV40 Tag peptides, where as complete tumour immunity was
      observed in mice immunized with rTag. Although protective tumour immunity was
      also observed in mice immunized with DNA, negligible levels of antibodies to SV40
      Tag were detected. Examination of the cytotoxic T lymphocyte (CTL) activity in
      mice injected with the SV40 Tag-DNA construct revealed Tag-specific lysis of
      syngeneic SV40-transformed tumour cells. Conversely, little to no CTL activity
      was detected in mice immunized with rTag. However, antigen-specific antibodies
      from rTag immunized mice were capable of mediating antibody-dependent cell
      mediated cytotoxicity against SV40-transformed cells. These data indicate that
      the immune mechanisms elicited for protection against SV40 induced tumours in
      mice appeared to be dependent on the vaccination strategy employed and included
      both humoral and cell-mediated immune responses.

PMID- 9776256
TI  - SV40 as an oncogenic virus and possible human pathogen.

PMID- 9776257
TI  - SV40 expression in human neoplastic and non-neoplastic tissues: perspectives on
      diagnosis, prognosis and therapy of human malignant mesothelioma.
AB  - We have recently demonstrated the association of SV40 and human pleural malignant
      mesothelioma. Here, we have investigated whether SV40 viral sequences may be
      associated with other human tumours or other non-neoplastic pathology and whether
      SV40 DNA or protein expression may be of diagnostic, prognostic or therapeutic
      relevance. DNA was extracted from paraffin embedded tissues. SV40, JC and BK
      viral sequences were detected by the polymerase chain reaction and molecular
      hybridization with specific probes. The screening with three different sets of
      SV40-related primers demonstrated that 7/18 (38.8%) mesothelioma specimens were
      SV40 positive as well as 5/18 (27.7%) tubercular pleural lesions. None of the 18
      lung cancers, nor the 20 pleural non-specific inflammatory specimens tested were
      positive. Twenty-five blood samples and 18 urinary sediments from MM patients
      were also negative. We have also found that SV40 Tag proteins are present in
      mesothelioma cells and tumours. Tag proteins may interfere with tumour suppressor
      gene products, such as p53. Preliminary results suggest that wild type p53
      transgene expression, obtained after infection with recombinant adenovirus
      (AdCMV.p53), inhibited in vitro and in vivo proliferation, inducing apoptosis of
      mesothelioma cells. Infections with control viruses were ineffective. Thus, SV40
      DNA and Tag expression in mesothelioma tumour cells, though probably not relevant
      for diagnostic or prognostic purposes, may be crucial for innovative gene therapy
      strategies.

PMID- 9776258
TI  - Simian virus 40 (SV40): a possible human polyomavirus. Bibliography of suggested
      texts.

PMID- 9776260
TI  - Advancing medical care: the role of nuclear medicine in radioguided surgery.

PMID- 9776261
TI  - Minimally invasive radioguided parathyroidectomy: an endocrine surgeon's
      perspective.

PMID- 9776262
TI  - Wake-up call: can you protect yourself and your nuclear medicine practice from
      fraud and abuse?

PMID- 9776263
TI  - Nitrogen-13-ammonia and oxygen-15-water estimates of absolute myocardial
      perfusion in left ventricular ischemic dysfunction.
AB  - Measurements of resting myocardial blood flow (MBF) in patients with chronic left
      ventricular ischemic dysfunction by 15O-water with 13N-ammonia and PET have
      yielded conflicting results. The aim of this study was to perform a head-to-head
      comparison of both tracers in the same patient population and to answer the
      question of whether distinctive tracer properties account for differences in
      estimates of MBF in chronically dysfunctional myocardium by both tracers.
      METHODS: A total of 30 patients with chronic dysfunction of the anterior
      myocardial wall due to significant left anterior descending coronary artery
      disease underwent PET measurements of absolute MBF in the anterior wall by use of
      15O-water and 13N-ammonia before coronary revascularization by either coronary
      artery bypass graft (n = 24) or percutaneous transluminal coronary angioplasty (n
      = 6). Improvement of regional contractile function was assessed by two
      dimensional echocardiography at a mean of 7.5 +/- 2.1 mo after revascularization.
      As judged from the changes in anterior myocardial wall motion after
      revascularization, patients were considered to have either reversibly (n = 16) or
      persistently (n = 14) dysfunctional myocardium. Estimates of MBF by 15O-water and
      13N-ammonia, obtained in every patient before revascularization, were compared
      among the two patient groups by use of previously validated methods. RESULTS:
      With 13N-ammonia, resting regional MBF was significantly higher in reversibly as
      opposed to persistently dysfunctional segments [84 +/- 8 versus 48 +/- 6 ml (min
      x 100 g)(-1), mean +/- s.e.m., p < 0.01]. By contrast, no such difference was
      found when using 15O-water to measure MBF [74 +/- 6 versus 86 +/- 9 ml (min x 100
      g)(-1), p = ns]. This was mainly due to the fact that the perfusable tissue
      fraction (PTF), a fitted parameter of the 15O-water model, was significantly
      higher in reversibly as opposed to persistently dysfunctional segments (0.63 +/-
      0.03 versus 0.50 +/- 0.03, p < 0.05). As a consequence, the 15O-water perfusable
      tissue index (PTI), which is the ratio of the PTF to the anatomical tissue
      fraction, was greater in reversibly dysfunctional as opposed to persistently
      dysfunctional segments (1.07 +/- 0.07 versus 0.79 +/- 0.05, p < 0.01).
      CONCLUSION: This study demonstrates significant differences in MBF estimates
      between 15O-water and 13N-ammonia in chronically dysfunctional ischemic
      myocardium. Our results indicate that the 15O-water method yields higher absolute
      MBF values than the 13N-ammonia approach. Our results also support the use of PTI
      as a marker of myocardial tissue viability.

PMID- 9776264
TI  - Safety of dobutamine-atropine stress myocardial perfusion scintigraphy.
AB  - Dobutamine stress testing is increasingly used for the diagnosis and functional
      evaluation of coronary artery disease. However, the relationship between
      myocardial perfusion abnormalities and complications of the test has not been
      studied. METHODS: We studied the hemodynamic profile, safety and feasibility of
      dobutamine (up to 40 microg/kg/min)-atropine (up to 1 mg) stress myocardial
      perfusion SPECT imaging (with 201TI, 99mTc-MIBI or tetrofosmin) in a consecutive
      series of 1076 patients (age = 59 +/- 11 yr, 50% with previous myocardial
      infarction) referred for evaluation of myocardial ischemia. RESULTS: No
      infarction or death occurred during the test. The test was considered feasible
      (achievement of 85% of the target heart rate or an ischemic endpoint) in 1005
      patients (94%). Hypotension (systolic blood pressure drop > or = 40 mm Hg)
      occurred in 37 patients (3.4%). Independent predictors were higher baseline
      systolic blood pressure (p < 0.0001), number of ischemic segments (p < 0.05) and
      age (p < 0.05). Supraventricular tachyarrhythmias occurred in 48 patients (4.4%).
      Independent predictors were fixed perfusion defect (infarction) score (p < 0.005)
      and age (p < 0.05). Ventricular tachycardia occurred in 41 patients (3.8%).
      Independent predictors were infarction score (p < 0.01) and male gender (p <
      0.05). All arrhythmias terminated spontaneously or after metoprolol
      administration. CONCLUSION: Dobutamine-atropine myocardial perfusion scintigraphy
      is a feasible method for the evaluation of coronary artery disease with a safety
      profile and feasibility comparable to those reported for dobutamine stress
      echocardiography. Patients with more severe fixed perfusion abnormalities are at
      a higher risk of developing tachyarrhythmias during the test.

PMID- 9776265
TI  - Physiological fluctuation of the human left ventricle sympathetic nervous system
      assessed by iodine-123-MIBG.
AB  - It has been proposed that sympathetic nervous system pathophysiology is involved
      in the development of cardiovascular disorders. Since cardiac adrenergic activity
      has been difficult to assess in humans, physiological changes in the sympathetic
      nervous system in the human left ventricle remain unclear. METHODS: To determine
      if age and gender influence the sympathetic nervous function of the left
      ventricle, 300 angiographically normal subjects (170 men, 130 women; age range 40
      79 yr) had 123I-metaiodobenzylguanidine (MIBG) cardiac imaging. Regional
      quantitative analysis of MIBG uptake and washout rate was performed. RESULTS: Men
      and women had prominent age-related decreases in MIBG uptake in the inferior and
      lateral walls (r2 = 0.34, p <0.0001 for both). Both genders had a significant
      positive correlation between regional washout rate and age in each region. In
      contrast to men, women had strong positive correlations in all regions (r2 =
      0.54, p <0.0001 in the anterior wall, r2 = 0.56, p <0.0001 in the lateral wall
      and r2 = 0.44, p <0.0001 in the inferior wall). According to the decade-by-decade
      analysis of washout rate, women had a significantly lower washout than men under
      50 yr in every region and a significantly higher washout in the lateral wall than
      men over 70 yr. CONCLUSION: The sympathetic nervous system in the human left
      ventricle showed age- and gender-related regional changes. The findings suggested
      that men have high sympathetic nerve activity from a younger age, and women have
      a progressive increase in sympathetic nerve activity with aging. These changes
      may contribute to the age and gender differences in the incidence and development
      of cardiac disorders.

PMID- 9776266
TI  - Intra-individual comparison of 3(R)-BMIPP and 3(S)-BMIPP isomers in humans.
AB  - The racemic 15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid (BMIPP) is
      currently used at several centers for myocardial metabolic imaging with SPECT.
      Recently, the 3(R)-BMIPP isomer showed a 20%-25% higher myocardial uptake and
      lower liver uptake than 3(S)-BMIPP in fasted rats. The aim of this study was to
      determine if these differences in myocardial and liver uptake also occur in
      humans. METHODS: Iodine-123-labeled 3(R)-BMIPP and 3(S)-BMIPP isomers were
      injected at rest, on two separate days, in six patients with stable coronary
      artery disease. Dual-head, whole-body scintigraphy was performed 20 min and 3 hr
      after injection. SPECT cardiac imaging was performed 60 min after injection.
      RESULTS: Myocardial activity averaged (% injected dose +/- s.d.) 3.15 +/- 0.49
      versus 3.01 +/- 0.44 at 20 min (p = ns) and 2.64 +/- 0.38 versus 2.55 +/- 0.41 at
      3 hr postinjection (p = ns) for the 3(R)-BMIPP and 3(S)-BMIPP isomers,
      respectively. Liver activity averaged 9.50 +/- 1.18 versus 9.44 +/- 0.66 at 20
      min and 5.33 +/- 0.64 versus 5.43 +/- 0.66 at 3 hr, respectively (p = ns). SPECT
      showed no difference in the distribution of the two isomers between normal and
      infarcted myocardium. CONCLUSION: There is no significant difference in
      myocardial and liver distribution of the 3(R)-BMIPP and 3(S)-BMIPP isomers in
      humans.

PMID- 9776267
TI  - Impaired regional fatty acid uptake and systolic dysfunction in hypertrophied
      right ventricle.
AB  - Little information is available regarding the determinants of systolic
      contractile function of the hypertrophied right ventricle (RV). The purpose of
      this study was to clarify the relationship between myocardial metabolism and
      contractile function in the hypertrophied RV due to pulmonary hypertension (PH).
      METHODS: Iodine-123-labeled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid
      (BMIPP) and 99mTc-sestamibi (MIBI) SPECT were performed to calculate the RV-to
      left ventricle (LV) tracer uptake ratio (RV/LV) in 21 patients with PH (6 with
      primary PH and 15 with chronic thromboembolic PH). The patients also underwent
      electron-beam CT to assess RV ejection function (RVEF) and percentage systolic
      wall thickening (%SWT) and right heart catheterization to measure mean pulmonary
      arterial pressure (mPAP). RESULTS: There were significant positive correlations
      between mPAP and MIBI-RV/LV (r = 0.89, p < 0.001) and between mPAP and BMIPP
      RV/LV (r = 0.86, p < 0.001). However, 8 patients showed lower BMIPP-RV/LV than
      MIBI-RV/LV, indicating the impairment of myocardial fatty acid uptake in the RV.
      These patients had lower RVEF and %SWT compared to those with normal myocardial
      fatty acid uptake (RVEF = 28% +/- 10% compared to 40% +/- 9% and %SWT = 33% +/-
      27% compared to 74% +/- 30%, respectively; p < 0.05 for both comparisons).
      Although mPAP did not differ between the groups, the RVEF-mPAP and %SWT-mPAP
      regression lines drawn from the patients with impaired myocardial fatty acid
      uptake were located below the lines from the patients with normal myocardial
      fatty acid uptake, suggesting disproportionately decreased RV myocardial
      contractility for a given mPAP in patients with impaired myocardial fatty acid
      uptake. The patients with the impaired fatty acid uptake in the RV had a
      significantly higher death rate (log-rank test, p < 0.05). CONCLUSION: The
      results from this preliminary study suggest that myocardial fatty acid uptake is
      impaired in the failing hypertrophied RV due to PH.

PMID- 9776268
TI  - Absent myocardial iodine-123-BMIPP uptake and platelet/monocyte CD36 deficiency.
AB  - Global absence of myocardial 123I-15-(p-iodophenyl)-3-(R,S)-methyl pentadecanoic
      acid (BMIPP) uptake is occasionally noted, and it reflects myocardial long-chain
      fatty acid uptake abnormality. CD36, a membrane glycoprotein expressed on
      platelet, monocyte and endothelial cells, may contribute to myocardial fatty acid
      transport, and its deficiency has been reported in a small subset of the
      population. We hypothesized that CD36 deficiency may be related to absent
      myocardial BMIPP uptake. Thus, we investigated CD36 expression of
      platelet/monocyte in patients with absent myocardial BMIPP uptake. METHODS:
      Peripheral blood of 7 patients with global absence of myocardial BMIPP uptake (3
      of 7 patients in one family) and 3 control subjects were examined in flow
      cytometric analysis. Platelet/monocyte surface CD36 was detected by using OKM5,
      an anti-CD36 mouse monoclonal antibody. RESULTS: There were no apparent
      relationships between specific clinical symptoms and absent myocardial BMIPP
      uptake. None of the blood samples of the 7 patients were stained with OKM5 on the
      platelet/monocyte cell surface, indicating that all of these patients were Type I
      CD36-deficient subjects. In contrast, all the control subjects showed normal
      staining. CONCLUSION: The fact that rare Type I CD36 deficiency was observed in
      all patients with absent myocardial BMIPP uptake suggests that CD36 plays a role
      in the myocardial long-chain fatty acid uptake process in humans.

PMID- 9776269
TI  - Comparison of fatty acid tracers FTHA and BMIPP during myocardial ischemia and
      hypoxia.
AB  - To study the sensitivity of two fatty acid tracers to changes in beta-oxidation,
      the myocardial retention kinetics of 125I-iodine-15-(p-iodophenyl)-3(R,S)
      methylpentadecanoic acid (BMIPP) and 14-18F-fluoro-6-thia-heptadecanoic acid
      (FTHA) were compared in states of oxygen deprivation due to ischemia and hypoxia.
      METHODS: Nineteen swine were studied by extracorporeal perfusion of the three
      coronary arteries. Fatty acid beta-oxidation rates were determined by infusion of
      tritiated palmitate into the left anterior descending artery (LAD) and by
      measurement of labeled water production in the LAD perfusion bed. After a
      baseline period of 30 min, animals were divided into three groups and subjected
      to a 50-min intervention period. For the control group, there was no change in
      perfusion; for the ischemia group, there was a 60% decrease in LAD perfusion; and
      for the hypoxia group, the perfusion rate was unchanged, but venous blood was
      used as the LAD perfusate. Continuous infusion of FTHA and BMIPP into the LAD
      started 10 min into the intervention period and continued until the end of the
      intervention period. Retention rates of the two tracers were compared between the
      LAD and circumflex perfusion beds. RESULTS: No difference in beta-oxidation rate
      occurred from the baseline to the intervention period in the control group. A 50%
      reduction in beta-oxidation occurred in the ischemia group, and an 80% reduction
      occurred in the hypoxia group. No difference in retention of BMIPP or FTHA
      occurred in the control group. In the ischemia group, reduction in retention of
      both tracers occurred. However, in the hypoxia group, FTHA uptake was unchanged,
      whereas BMIPP retention increased compared to the circumflex arterial bed.
      CONCLUSION: Decreased retention of both BMIPP and FTHA occurred with ischemia,
      despite the known differences in metabolism of the two tracers. This difference
      in metabolism was further highlighted in the setting of hypoxia with increased
      BMIPP uptake. Thus, these results suggest that uptake of both FTHA and BMIPP
      tracks reduction of fatty acid utilization in myocardial ischemia but fails in
      tracking reduction of fatty acid oxidation during hypoxia.

PMID- 9776270
TI  - Myocardial uptake of the fatty acid analog 14-fluorine-18-fluoro-6-thia
      heptadecanoic acid in comparison to beta-oxidation rates by tritiated palmitate.
AB  - The fatty acid tracer 14-18F-fluoro-6-thia-heptadecanoic acid (FTHA) is a
      metabolically trapped tracer of exogenous fatty acid utilization. The objectives
      of this study were to determine the relationship of FTHA uptake to changes in
      perfusion and fatty acid oxidation and to confirm the retention of FTHA in the
      mammalian heart. METHODS: Six pigs with extracorporeal perfusion of the left
      anterior descending artery (LAD) and cannulation of the LAD vein were studied.
      The extraction fraction (EF) of FTHA, measured from LAD arterial and venous blood
      samples, was compared to beta-oxidation rates, determined by water production
      from tritiated palmitate. After a baseline period, changes in FTHA EF were
      measured in 15-min periods of hyperemia, control (baseline flow rate) and lactate
      infusion. After the lactate infusion, FTHA infusion was terminated, and a 15-min
      washout period was observed. RESULTS: Beta-oxidation rate was unchanged from the
      baseline period during the hyperemic and control periods. With lactate infusion,
      the expected myocardial preference for lactate was noted, with a decline in
      exogenous fatty acid oxidation. Fluorine-18-FTHA EF paralleled the changes in
      beta-oxidation, with a decrease in EF during lactate infusion. Increase in
      perfusion was associated with a decrease in FTHA EF, compared to control, such
      that the product of flow and extraction was maintained. A linear relationship of
      FTHA EF to fractional tritiated water production was found. Washout analysis
      confirmed minimal washout of tracer at 15 min after termination of infusion.
      Organic solvent extraction of tissue samples suggested that the majority of
      tissue radioactivity was protein-bound. CONCLUSION: In the extracorporeally
      perfused mammalian heart, FTHA EF declined during suppression of beta-oxidation
      with lactate infusion and alteration in perfusion without change in fatty acid
      oxidation rate. The linear relationship of FTHA EF with fractional water
      production from tritiated palmitate further confirms a correlation of the uptake
      of FTHA with fatty acid beta-oxidation rate and supports the utility of FTHA in
      the noninvasive determination of fatty acid oxidation rate. Furthermore, the
      trapped nature of the tracer may allow the use of graphical analysis for the
      quantification of beta-oxidation rates.

PMID- 9776271
TI  - Generation of myocardial factor images directly from the dynamic oxygen-15-water
      scan without use of an oxygen-15-carbon monoxide blood-pool scan.
AB  - The measurement of regional myocardial blood flow (MBF) with H2(15)O and PET
      requires an additional C15O blood-pool scan for the purpose of region of interest
      (ROI) definition. This additional scan results in a substantially increased
      radiation dose, study duration and risk of movement artifacts. Therefore, a
      method was developed to generate myocardial factor images directly from the
      dynamic H2(15)O study without the need for a C15O scan. METHODS: The factor
      sinograms were generated by means of linear dimension reduction of the dynamic
      sinograms, where the required variate and covariate factors (myocardial and blood
      time-activity curves) were modeled from the lung time-activity curve. The factor
      images were generated by iterative reconstruction. RESULTS: No significant
      difference was found between MBF values from ROIs drawn on the traditional images
      (using the C15O scan) and those drawn on the factor images. CONCLUSION: It is
      possible to generate myocardial images directly from the dynamic H2(15)O study,
      so that the C15O scan can be omitted from MBF studies. The proposed method is
      robust and results in nearly optimal signal-to-noise ratios in the factor images.

PMID- 9776272
TI  - D2 receptor imaging with iodine-123-iodobenzamide brain SPECT in infants with
      hypoxic-ischemic brain injury.
AB  - The purpose of this study was to evaluate the striatal dopamine D2 receptor
      density in infants with perinatal hypoxic-ischemic brain injury (HIBI) using 123I
      iodobenzamide (IBZM) brain SPECT and to correlate the findings with the severity
      of HIBI and neurologic outcome. METHODS: Twenty infants who were diagnosed to
      have perinatal HIBI were included in this study. They were classified as having
      mild (n = 6), moderate (n = 10) or severe (n = 4) HIBI according to their
      neurologic findings at birth using the criteria of Sarnat and Sarnat. Neurologic
      outcome of these infants was determined by serial neurologic examinations and the
      Denver developmental screening test; 10 infants recovered without any deficit and
      the remaining 10 were affected to a degree varying from motor impairment to
      cerebral palsy. All 20 infants were examined using 123I-IBZM brain SPECT at age
      7.8 +/- 2.3 mo. Transaxial slices were obtained 2 hr after intravenous injection
      of 300 micro ci (11.1 MBq) 123I-IBZM and the activity ratios of striatal to
      occipital cortex (ST/OC) were calculated. RESULTS: The mean ST/OC ratios in
      patients with mild, moderate and severe HIBI (1.219 +/- 0.078, 1.097 +/- 0.069
      and 0.813 +/- 0.140, respectively) were significantly different from each other
      (p = 0.001). The infants who recovered from HIBI without any neurologic sequelae
      had higher mean ST/OC ratios than the others (1.184 +/- 0.010 versus 0.969 +/-
      0.160, p = 0.002). CONCLUSION: The results of this study show that in infants
      with HIBI, striatal D2 receptor density decreases as the severity of injury
      increases. The D2 receptor density is higher in infants who recover without
      neurologic deficits compared to those who are affected neurologically. Dopamine
      D2 receptor imaging can be used to assess the severity of HIBI in children.

PMID- 9776273
TI  - Technetium-99m-HMPAO SPECT and MRI of brain in patients with neuro-Behcet's
      syndrome.
AB  - Involvement of the brain is one of the most important complications of Behcet's
      disease (BS). It is difficult to diagnose, however, because of the lack of
      effective imaging methods. METHODS: Thirteen BS patients with neuropsychiatric
      symptoms or signs [Neuro-Behcet's syndrome (NBS)] were included in this study. We
      combined two routine brain imaging modalities-brain SPECT with 99mTc-hexamethyl
      propyleneamine oxime (HMPAO) and brain MRI-with clinical manifestations to
      diagnose brain involvement. RESULTS: Technetium-99m-HMPAO brain SPECT findings
      were abnormal in 100% (13/13) of patients. Brain MRI findings were abnormal in
      31% (4/13) of patients. Gray matter was involved more commonly than white matter.
      In the gray matter, the cerebral cortex was the most commonly involved area and
      the cerebellum was the least commonly involved area in NBS. CONCLUSION: SPECT is
      a more sensitive and useful tool in detecting brain involvement in NBS patients
      compared with brain MRI. The combination of HMPAO and MRI is necessary to detect
      brain lesions in both gray and white matter in NBS.

PMID- 9776274
TI  - Technetium-99m-HMPAO brain SPECT in neonates with hypoglycemic encephalopathy.
AB  - Regional brain injury in three neonates with hypoglycemic encephalopathy are
      presented using serial 99mTc-hexamethyl propyleneamine oxime (HMPAO) SPECT and,
      for comparison, MRI. During the acute stage, both 99mTc-HMPAO SPECT and MRI
      reveal abnormalities in the posterior cerebrum. Technetium-99m-HMPAO SPECT
      reveals further areas of insult, for example the frontal lobes. The degree of
      hypoperfusion correlates with the clinical severity of hypoglycemia during the
      neonatal period and subsequent neurological sequelae. Follow-up with HMPAO SPECT
      several months after insult demonstrates persistent hypoperfusion in some areas,
      mainly in the occipital and posterior parietal regions. MRI can depict
      morphological changes with superior resolution. Because morphological change
      generally follows slowly after functional change, MRI is less sensitive than
      HMPAO SPECT in detecting and predicting the extent of hypoglycemic cerebral
      injury during the acute phase. HMPAO SPECT during the acute stage is a valuable
      tool for evaluating the extent and severity of brain injury in neonates with
      hypoglycemic encephalopathy.

PMID- 9776275
TI  - Quantitative comparison of three- and two-dimensional PET with human brain
      studies.
AB  - The aim of this study was to test the quantitation accuracy of three-dimensional
      PET in brain scanning. METHODS: Three-dimensional data from 11 human subjects
      were tested using 11C-dihydrotetrabenazine, 11C-Schering 23390 and 18F-FDG as
      tracers. Two-dimensional scans were performed on the same subjects and the
      distribution volume, distribution volume ratio and local metabolic rate of
      glucose (LMRGlu) values obtained from these were used as reference. Three
      dimensional data were processed as follows: iterative convolution subtraction
      scatter correction, detector normalization including radial and axial geometric
      factors, attenuation correction extracted from a two-dimensional transmission
      scan, Kinahan-Rogers reconstruction and region-of-interest-based sensitivity
      calibration. RESULTS: No major systematic differences between the two methods
      were found. The agreement between the two-dimensional and three-dimensional data
      was within 5%. Although statistical analysis generally did not show this
      difference to be significant, reliability analysis indicated that comparing two
      dimensional and three-dimensional data might introduce some inaccuracies.
      CONCLUSION: Three-dimensional PET yields quantitatively valid results for brain
      scanning.

PMID- 9776276
TI  - Significance of nonuniform attenuation correction in quantitative brain SPECT
      imaging.
AB  - The purposes of this study were to develop a method for nonuniform attenuation
      correction of 123I emission brain images based on transmission imaging with a
      longer-lived isotope (i.e., 57Co) and to evaluate the relative improvement in
      quantitative SPECT images achieved with nonuniform attenuation correction.
      METHODS: Emission and transmission SPECT scans were acquired on three different
      sets of studies: a heterogeneous brain phantom filled with 1231 to simulate the
      distribution of dopamine transporters labeled with 2beta-carbomethoxy-3beta-(4
      123I-iodophenyl)tropane (123I-beta-CIT); nine healthy human control subjects who
      underwent transmission scanning using two separate line sources (57Co and 123I);
      and a set of eight patients with Parkinson's disease and five healthy control
      subjects who received both emission and transmission scans after injection of
      123I-beta-CIT. Attenuation maps were reconstructed using a Bayesian transmission
      reconstruction algorithm, and attenuation correction was performed using Chang's
      postprocessing method. The spatial distribution of errors within the brain was
      obtained from attenuation correction factors computed from uniform and nonuniform
      attenuation maps and was visualized on a pixel-by-pixel basis as an error image.
      RESULTS: For the heterogeneous brain phantom, the uniform attenuation correction
      had errors of 2%-6.5% for regions corresponding to striatum and background,
      whereas nonuniform attenuation correction was within 1%. Analysis of 123I
      transmission images of the nine healthy human control subjects showed differences
      between uniform and nonuniform attenuation correction to be in the range of 6.4%
      16.0% for brain regions of interest (ROIs). The human control subjects who
      received transmission scans only were used to generate a curvilinear function to
      convert 57Co attenuation values into those for 123I, based on a pixel-by-pixel
      comparison of two coregistered transmission images for each subject. These values
      were applied to the group of patients and healthy control subjects who received
      transmission 57Co scans and emission 123I scans after injection of 123I-beta-CIT.
      In comparison to nonuniform attenuation correction as the gold standard, uniform
      attenuation with the ellipse drawn around the transmission image caused an
      approximately 5% error, whereas placement of the ellipse around the emission
      image caused a 15% error. CONCLUSION: Nonuniform attenuation correction allowed a
      moderate improvement in the measurement of absolute activity in individual brain
      ROIs. When images were analyzed as target-to-background activity ratios, as is
      commonly performed with 123I-beta-CIT, these outcome measures showed only small
      differences when Parkinson's disease patients and healthy control subjects were
      compared using nonuniform, uniform or even no attenuation correction.

PMID- 9776278
TI  - FDG uptake, GLUT-1 glucose transporter and cellularity in human pancreatic
      tumors.
AB  - We previously reported that grading of GLUT-1 glucose transporter expression was
      related closely to FDG accumulation in FDG PET in human cancers. But in this
      strong GLUT-1 expression group, there was an enormous range of standardized
      uptake values (SUVs) within them. METHODS: To evaluate other factors determining
      the FDG PET uptake, FDG PET was performed in 36 preoperative patients (mean age
      62.0 yr) suspected of having pancreatic tumors, including 33 malignant and 3
      benign neoplastic tumors. FDG uptake at 50 min after injection of 185 MBq 18F-FDG
      with > 5 hr fasting condition was semiquantitatively analyzed as SUVs. The GLUT-1
      expression was studied by immunohistochemistry of paraffin sections from these
      tumors after the operation using the antiGLUT-1 antibody. The number of tumor
      cells within a 5- x 5-mm square was counted manually using x200 magnification
      photographs and was graded immunohistochemically as strong, weak or negative.
      RESULTS: In all 36 cases there were 3 cases of GLUT-1 negative, 8 of GLUT-1 weak
      positive and 25 of GLUT-1 strong positive. In all cases, the total number of
      tumor cells had no significant value for SUVs. Among 33 GLUT-1 positive cases,
      the number of GLUT-1 positive tumor cells correlated significantly with SUVs (p <
      0.01). Only in 25 strong grade cases, the number of GLUT-1 strong positive tumor
      cells had a more significant value for SUVs (p < 0.005). Computational
      multivariate analysis using multiple regression for SUVs was performed evaluating
      the five variables as follows: tumor size, GLUT-1 immunohistochemical grading,
      number of total tumor cells, number of total GLUT-1 positive tumor cells and
      number of GLUT-1 strong positive cells. This analysis revealed that only the
      variable, the number of GLUT-1 strong positive cells, had a significant
      regression coefficient for SUVs (standard regression coefficient = 0.855, p <
      0.0001). CONCLUSION: These data indicate that GLUT-1 expression plays an
      essential role in higher FDG accumulation in pancreatic tumor FDG PET, and the
      cellularity has a significant influence on SUVs only in the condition of GLUT-1
      strong positive expression.

PMID- 9776280
TI  - Iodine-131-MIBG therapy of a patient with carcinoid liver metastases.
AB  - Iodine-13I-metaiodobenzylguanidine (MIBG) is highly concentrated by >60% of
      carcinoid metastases and thus provides a therapeutic opportunity. METHODS: A
      symptomatic patient with carcinoid liver metastases, unresponsive to chemotherapy
      combined with interferon-alpha, was subsequently treated with 131I-MIBG. RESULTS:
      Radionuclide therapy, which was without significant side effects, resulted in
      symptomatic improvement and reduced urinary 5-hydroxyindoleacetic acid levels. No
      new metastases were observed for 15 mo after 131I-MIBG therapy. Gross cystic
      change occurred in existing liver metastases, presumably as a result of ischemic
      necrosis. Surgical deroofing and aspiration of cysts led to regeneration of
      normal liver tissue. CONCLUSION: Iodine-131-MIBG therapy can provide prolonged
      symptomatic relief and improved quality of life in patients with metastatic
      carcinoid disease unresponsive to other therapies. The antitumor effect of 131I
      MIBG was accompanied by few side effects, suggesting that this therapy should be
      considered in symptomatic patients with an early stage of disease.

PMID- 9776279
TI  - Feasibility of tumor imaging using L-3-[iodine-123]-iodo-alpha-methyl-tyrosine in
      extracranial tumors.
AB  - L-3-[123I]-Iodo-alpha-methyl-tyrosine (IMT) is a modified amino acid. It is
      reported to be avidly taken up in brain tumors, reflecting amino acid transport
      and is suitable for SPECT. METHODS: To determine whether tumors outside the brain
      can also accumulate this tracer, we injected 300-450 MBq IMT into 20 patients
      with different tumors [5 breast cancers, 4 lung tumors (1 benign), 2 carcinoid
      liver metastases, 4 soft-tissue tumors (1 benign), 3 malignant lymphomas and 2
      primary brain tumors]. Tumor size ranged from 1-12 cm. Imaging was repeated after
      radiotherapy in two patients with breast cancer. Histology was available in all
      cases. Dynamic scans, whole-body imaging and SPECT were performed during the
      first hour and 3 hr after injection. Plasma samples were analyzed for IMT, free
      1231 and other metabolites. RESULTS: All primary tumors were visualized. Tumor-to
      background ratios ranged from 1.1 to 3.8 on planar and from 1.3 to 6.2 on SPECT
      images. Tumor uptake peaked in the first hour. Two carcinoid lesions in the liver
      tumors exhibited no IMT uptake above liver background. Tumor-to-background ratios
      in a benign bone inflammatory process and a focal pulmonary vasculitis were less
      than 1.2 (planar) and 1.9 (SPECT) and could be differentiated from uptake in all
      malignant nonbrain tumors. IMT was rapidly cleared from the plasma [3.6% +/- 0.6%
      (mean +/- s.d.) injected dose/liter at 10 min postinjection]. Minor in vivo
      deiodination was present (<1% of injected dose 1 hr postinjection). No other
      metabolites were found. Normal distribution consists of some uptake in the brain,
      liver, spleen, muscles, pancreatic region and intestinal structures and massive
      uptake and excretion in the kidneys and bladder. CONCLUSION: IMT has potential as
      a metabolic tracer in tumors outside the brain.

PMID- 9776281
TI  - Marrow toxicity and radiation absorbed dose estimates from rhenium-186-labeled
      monoclonal antibody.
AB  - Estimates of radiation absorbed dose to the red marrow (RM) would be valuable in
      treatment planning for radioimmunotherapy if they could show a correlation with
      clinical toxicity. In this study, a correlation analysis was performed to
      determine whether estimates of radiation absorbed dose to the bone marrow could
      accurately predict marrow toxicity in patients who had received 186Re-labeled
      monoclonal antibody. METHODS: White blood cell and platelet count data from 25
      patients who received 186Re-NR-LU-10 during Phase I radioimmunotherapy trials
      were analyzed, and the toxicity grade, the fraction of the baseline counts at the
      nadir (percentage baseline) and the actual nadir were used as the indicators of
      marrow toxicity. Toxicity was correlated with various predictors of toxicity.
      These predictors included the absorbed dose to RM, the absorbed dose to whole
      body (WB) and the total radioactivity administered. RESULTS: Percentage baseline
      and grade of white blood cells and platelets all showed a moderate correlation
      with absorbed dose and radioactivity administered (normalized for body size). The
      percentage baseline platelet count was the indicator of toxicity that achieved
      the highest correlation with the various predictors of toxicity (r = 0.73-0.79).
      The estimated RM absorbed dose was not a better predictor of toxicity than either
      the WB dose or the total radioactivity administered. There was substantial
      variation in the blood count response of the patients who were administered
      similar radioactivity doses and who had similar absorbed dose estimates.
      CONCLUSION: Although there was a moderately good correlation of toxicity with
      dose, the value of the dose estimates in predicting toxicity is limited by the
      patient-to-patient variability in response to internally administered
      radioactivity. In this analysis of patients receiving 186Re-labeled monoclonal
      antibody, a moderate correlation of toxicity with dose was observed but marrow
      dose was of limited use in predicting toxicity for individual patients.

PMID- 9776282
TI  - Intratumoral injection of rhenium-188 microspheres into an animal model of
      hepatoma.
AB  - Intratumoral injection of 90Y microspheres is a potential alternative in the
      treatment of primary liver tumor. However, complicated preparation and lack of a
      gamma ray for imaging are the disadvantages of 90Y. In this study, we used 188Re,
      a generator-produced radioisotope with 155-keV gamma ray emission, to label
      microspheres. After intratumoral injection of 188Re microspheres into rats with
      hepatoma, biodistributions and survival times were analyzed. METHODS: Twelve male
      rats with hepatoma were killed at 1, 24 and 48 hr (4 rats at each time point)
      after intratumoral injection of approximately 7.4 MBq 188Re microspheres. Samples
      of various organs were obtained and used to calculate the tissue concentrations.
      In addition, 30 male rats bearing hepatoma were divided into two groups (15 rats
      in each group) to evaluate survival time. Group 1 received intratumoral injection
      of 37 MBq 188Re microspheres, whereas Group 2 served as the control group and
      received an intratumoral injection of 0.1 ml normal saline only. Survival time
      was calculated from the day of injection to 2 mo after treatment. RESULTS:
      Radioactivity in the tumor was very high throughout. Biological half-time was
      170.8 hr. Radioactivity in the lung was 1.78% injected dose (i.d.)/g at 1 hr but
      declined rapidly over time. The concentration in the urine was approximately
      6.14% i.d./ml after the first hour and rapidly declined thereafter. The
      concentrations of radioactivity in other organs, such as normal liver, muscle,
      spleen, bone, testis and whole blood, were quite low throughout the study. Twelve
      of 15 (80%) of rats survived over 60 days after intratumoral injection of 188Re
      microspheres, whereas only 4 of 15 (26.7%) survived more than 60 days after
      injection of normal saline only. The difference between the groups was
      significant (p < 0.05). CONCLUSION: Rhenium-188 offers cost-effectiveness, on
      site availability, short half-life, energetic beta particle, emission of gamma
      photons for imaging, easy preparation, easy clinical administration and apparent
      lack of radiation leakage from the treated tumor. Direct intratumoral injection
      of 188Re microspheres is extremely attractive as a clinical therapeutic
      alternative in hepatoma patients.

PMID- 9776283
TI  - Carbon-11-thymidine and FDG to measure therapy response.
AB  - This study was performed to determine if PET imaging with 11C-thymidine could
      measure tumor response to chemotherapy early after the initiation of treatment.
      Imaging of deoxyriboneucleic acid biosynthesis, quantitated with 11C-thymidine,
      was compared with measurements of tumor energetics, obtained by imaging with 18F
      fluorodeoxyglucose (FDG). METHODS: We imaged four patients with small cell lung
      cancer and two with high-grade sarcoma both before and approximately 1 wk after
      the start of chemotherapy. Thymidine and FDG studies were done on the same day.
      Tumor uptake was quantified by standardized uptake values (SUVs) for both tracers
      by the metabolic rate of FDG and thymidine flux constant (K(TdR)) using regions
      of interest placed on the most active part of the tumor. RESULTS: In the four
      patients with clinical response to treatment, both thymidine and FDG uptake
      markedly declined 1 wk after therapy. Thymidine measurements of SUV and K(TdR)
      declined by 64% +/- 15% and 84% +/- 33%, respectively. FDG SUV and the metabolic
      rate of FDG declined by 51% +/- 9% and 63% +/- 23%, respectively. In the patient
      with metastatic small cell lung cancer who had disease progression, the thymidine
      SUV decreased by only 8% (FDG not done). In a patient with abdominal sarcoma and
      progressive disease, thymidine SUV was essentially unchanged (declined by 3%),
      whereas FDG SUV increased by 69%. CONCLUSION: Images show a decline in both
      cellular energetics and proliferative rate after successful chemotherapy. In the
      two patients with progressive disease, thymidine uptake was unchanged 1 wk after
      therapy. In our limited series, K(TdR) measurements showed a complete shutdown in
      tumor proliferation in patients in whom FDG showed a more limited decrease in
      glucose metabolism.

PMID- 9776284
TI  - Tumor cell spheroids as a model for evaluation of metabolic changes after
      irradiation.
AB  - Tumor cell spheroids provide a good model to evaluate the relationship between
      tumor volume and the number of viable cells in the volume with the uptake of
      metabolic tracers before and after therapy. They represent the only in vitro
      model that allows the determination of the activity per unit volume, a parameter
      which is relevant for interpretation of PET studies. The purpose of this study
      was to evaluate this model with respect to the uptake of 14C-FDG, 3H-methionine
      and 3H-thymidine with and without exposure to irradiation. METHODS: Spheroids of
      the human adenocarcinoma cell line SW 707 were incubated in media containing 14C
      FDG, 3H-methionine or 3H-thymidine for 1 hr at 1, 4, 8, 24 and 48 hr after
      exposure to a single radiation dose of 6 Gy together with control spheroids.
      Tracer uptake after incubation was expressed in cpm/ spheroid, cpm/1000 viable
      cells and cpm/0.01 mm3. In addition, the proliferative capacity of control and
      irradiated spheroids was determined using the clonogenic assay. RESULTS: Spheroid
      uptake of FDG decreased with time after irradiation, while the uptake per 1000
      viable cells was increased significantly. The activity per unit volume remained
      unchanged in comparison to control spheroids. Methionine uptake per spheroid was
      unchanged after irradiation because of the high increase in uptake per 1000
      viable cells. Uptake per unit volume also remained unchanged in comparison to
      controls. Thymidine uptake per 1000 viable cells did not change after irradiation
      but showed significant differences in uptake per spheroid and per unit volume
      compared to controls. The percentage of thymidine incorporated into the TCA
      precipitable fraction containing DNA was 50% in controls and decreased to 12% at
      24 hr after irradiation. The suppressed clonogenic capacity early after therapy
      recovered with the increase in thymidine uptake and with the increase in
      thymidine incorporation into DNA. CONCLUSION: The results show that the activity
      determined within a certain tumor volume is a balance between the increased
      tracer uptake by surviving cells after therapy and the lack of tracer uptake by
      dead cells, which still contribute to the tumor volume. Thus, the resulting
      unchanged activity per unit volume within the spheroid, as found for FDG and
      methionine, may not fully reflect therapy-induced metabolic changes in tumors.

PMID- 9776286
TI  - Bullets to magic bullets--and miles to go before we sleep.

PMID- 9776285
TI  - Gallium-68 chelate imaging of human colon carcinoma xenografts pretargeted with
      bispecific anti-CD44V6/anti-gallium chelate antibodies.
AB  - Recently, we demonstrated the feasibility of combining improved tumor-to-tissue
      contrasts and PET imaging for immunoscintigraphic tumor localization using a
      multistep targeting technique that consists of the administration of an
      antitumor/antihapten bispecific monoclonal antibody (BS-MAb), a blocker to
      saturate the antihapten binding sites of the BS-MAb that are still present in the
      circulation, and a low molecular weight Ga chelate, labeled with positron emitter
      68Ga, serving as the hapten. Due to this technique, the biodistribution of the
      radiolabeled hapten is governed mainly by the binding characteristics of both the
      antitumor and the antihapten part of the BS-MAb. For a future clinical
      implementation of the method, we investigated MAb VFF18, which is reactive with
      the adhesion molecule CD44V6, a tumor-associated antigen, and up-regulated in
      colon, squamous cell and pancreas carcinoma, and two anti-Ga chelate MAbs, which
      are highly selective for only one of the two enantiomers (optical isomers) of the
      inherently racemic Ga chelate. METHODS: From the VFF18 MAb and the anti-Ga
      chelate MAbs, two BS-MAbs containing the same antitumor parts, but different
      antihapten parts, were prepared and tested for multistep targeting in human colon
      carcinoma-bearing nude mice. RESULTS: Despite identical biodistributions of both
      BS-MAbs and their very similar affinities for the corresponding Ga chelate
      enantiomers, tumor uptake of the two enantiomers 1 hr postinjection was
      significantly different [8.7 +/- 1.9% versus 5.8% +/- 1.6% of the injected dose/g
      (%i.d./g)], with tumor-to-blood ratios being higher for the BS-MAb showing the
      lower tumor uptake (7.6 +/- 1.6 versus 4.7 +/- 0.6). From data obtained with each
      BS-MAb, a similar initial tumor binding of approximately 15.5%i.d./g, but
      different in vivo half-lives of the corresponding BS-MAb-enantiomer immune
      complexes, could be estimated. Pretargeting with a mixture of both BS-MAbs
      followed by the administration of the racemic Ga chelate resulted in the lowest
      tumor uptake (3.9% +/- 1.5%i.d./g). PET imaging of nude mice with the
      enantiomeric, as well as with the racemic, 68Ga chelate demonstrated a clear
      delineation of tumors against blood pool background. CONCLUSION: Multistep
      immunoscintigraphy with BS-MAbs markedly increases tumor-to-tissue ratios in nude
      mice and enables PET imaging. Using a BS-MAb containing MAb VFF18, a more
      sensitive localization of CD44V6-positive tumors in patients should also be
      obtained.

PMID- 9776287
TI  - Bone scintigraphy in the detection of chronic recurrent multifocal osteomyelitis.
AB  - In this study, we describe the importance of the whole-body bone scan in
      diagnosing the multifocality of chronic recurrent multifocal osteomyelitis (CRMO)
      and in distinguishing it from unifocal acute hematogenous osteomyelitis.
      MATERIALS: The medical records and two-phase, whole-body bone scans of 14
      patients (mean age 10.5 yr) with the diagnosis of CRMO, were retrospectively
      reviewed. The diagnosis of CRMO was based on bone biopsy in 9 patients and
      clinical course/laboratory findings in 5. Bone scans were evaluated for
      geographic and anatomic locations of their lesions. Correlative radiographs of
      areas of abnormal uptake were performed to assess the radiographic appearance of
      the lesions. RESULTS: The presentation of the disease was localized to one
      painful, tender and swollen periarticular site 86% of the time. The number of
      lesions detected by bone scan varied from 1-18 (mean 6). Most lesions were
      metaphyseal, proximal or distal tibial lesions. Purely sclerotic or mixed
      (sclerosis and lysis) lesions were found on radiographs. Bilateral lesions were
      seen in 64% of patients. Biopsies were negative for organisms in all patients and
      exhibited subacute or chronic histologic changes in most instances. Complications
      of chronic hyperemia included marked overgrowth (5), diffuse demineralization
      (1), angular deformity (1) and length discrepancy (1). CONCLUSION: The
      identification of the multifocal configuration of the disease process by two
      phase (soft-tissue and delayed) whole-body bone scintigraphy results in
      appropriate diagnosis and therapy of CRMO. Additional sites for possible bone
      biopsy become apparent for exclusion of other diagnoses. Supportive
      (nonsteroidal, anti-inflammatory medication) instead of antimicrobial therapy can
      be initiated with significant cost savings.

PMID- 9776288
TI  - Evaluation of glomerular filtration rate by camera-based method in both children
      and adults.
AB  - We describe a method to evaluate glomerular filtration rate (GFR) in both
      children and adults using 99mTc-diethylenetriamine pentaacetic acid (DTPA) and a
      gamma camera. METHODS: Renal scintigraphy with 99mTc-DTPA was performed in 40
      children and 92 adults with various degrees of renal function. The percent renal
      uptake at 2-2.5 min after tracer arrival in the kidney was determined with
      background subtraction and correction for soft-tissue attenuation and was
      correlated by linear regression analysis with GFR measured from two blood
      samples. A perirenal region of interest was used for background subtraction.
      Renal depth was computed using the equations determined or validated on the basis
      of CT measurements, and the attenuation coefficient was set at 0.12. The obtained
      regression equation was used to predict GFR. Renal function was also assessed by
      the Gates' method. RESULTS: Percent renal uptake was closely correlated with GFR
      normalized for body surface area in all patients (y = 15.958x - 2.94; r = 0.939).
      GFR was successfully predicted using the regression equation in both children and
      adults. Gates' method severely overestimated GFR in children and provided less
      accurate values even in adults than our method. CONCLUSION: The method presented
      here requires neither blood sampling nor additional imaging and allows estimation
      of GFR in both children and adults.

PMID- 9776290
TI  - Gastric emptying in male neurologic trauma.
AB  - Prolonged gastric emptying half-time (GET1/2) has been observed in several
      neurological disorders. Most patients with moderate to severe neurologic trauma
      (NT) initially do not tolerate enteral or nasogastric feedings. However, previous
      findings of altered gastric emptying (GE) in patients with NT have been
      questionable. Quantitative measurements of GE, to determine a possible mechanism
      for intolerance to enteral feeding, are lacking. In this study, we measured
      GET1/2 sec of solid and liquid meals by radionuclide imaging in men who were
      neurologic trauma patients. METHODS: A prospective study was conducted to assess
      GET1/2 in 30 men who were patients with spinal cord injuries (SCIs) and 20 men
      who were patients with head injuries (HIs) using radionuclide-labeled solid and
      liquid meals, respectively. Meanwhile, 18 and 14 male control subjects underwent
      the same imaging techniques for solid and liquid meals, respectively, to evaluate
      the normal ranges of solid and liquid GET1/2 sec (84.5 +/- 16.7 and 29.2 +/- 3.7
      min). RESULTS: In the 30 SCI patients, GET1/2 of solid meals was significantly
      prolonged (138.3 +/- 49.2 min, p < 0.05), and 53% (16/30) of patients had
      abnormal GET1/2. A more prolonged GET1/2 and a higher incidence of abnormal
      GET1/2 were observed in patients with high-level injury, when compared with
      patients with low-level injury (p < 0.05). In the 20 HI patients, GET1/2 of
      liquid meals was prolonged significantly (51.7 +/- 24.8 min, p < 0.05), and 65%
      (13/20) of patients had abnormal GET1/2. Coma, as indicated by the Glasgow Coma
      Scale score, was not a statistically significant factor influencing GET1/2 (p
      >0.05). CONCLUSION: NT can cause significantly prolonged GE, especially in
      patients with high-level SCI.

PMID- 9776289
TI  - Noninvasive quantitation of cerebral blood flow using oxygen-15-water and a dual
      PET system.
AB  - Measurement of the arterial input function is essential for quantitative
      assessment of physiological function in vivo using PET. However, frequent
      arterial blood sampling is invasive and labor intensive. Recently, a PET system
      has been developed that consists of two independent PET tomographs for
      simultaneously scanning the brain and heart, which should avoid the need for
      arterial blood sampling. The aim of this study was to validate noninvasive
      quantitation with this system for 15O-labeled compounds. METHODS: Twelve healthy
      volunteers underwent a series of PET studies after C15O inhalation and
      intravenous H2(15)O administration using a Headtome-V-Dual tomograph (Shimadzu
      Corp., Kyoto, Japan). The C15O study provided gated blood-pool images of the
      heart simultaneously with quantitative static blood-volume images of both the
      brain and heart. Weighted-integrated H2(15)O sinograms were acquired for
      estimating rate constant (K1) and distribution-volume (Vd) images in the brain,
      in addition to single-frame sinograms for estimating autoradiographic cerebral
      blood flow images. Noninvasive arterial input functions were determined from the
      heart scanner (left ventricular chamber) according to a previously developed
      model and compared directly to invasive input functions measured with an on-line
      beta probe in six subjects. RESULTS: The noninvasive input functions derived from
      this PET system were in good agreement with those obtained by continuous arterial
      blood sampling in all six subjects. There was good agreement between quantitative
      values obtained noninvasively and those using the invasive input function:
      average autoradiographic regional cerebral blood flow was 0.412 +/- 0.058 and
      0.426 +/- 0.062 ml/min/g, K1 of H2(15)O was 0.416 +/- 0.073 and 0.420 +/- 0.067
      ml/min/ml and Vd of H2(15)O was 0.800 +/- 0.080 and 0.830 +/- 0.070 ml/ml for the
      noninvasive and invasive input functions, respectively. In addition to the brain
      functional parameters, the system also simultaneously provided cardiac function
      such as regional myocardial blood flow (0.84 +/- 0.19 ml/min/g), left ventricular
      volume (132 +/- 22 mm at end diastole and 45 +/- 14 ml at end systole) and
      ejection fraction (66% +/- 5%). CONCLUSION: This PET system allows noninvasive
      quantitation in both the brain and heart simultaneously without arterial
      cannulation, and may prove useful in clinical research.

PMID- 9776291
TI  - Technetium-99m-HIDA scintigraphy versus endoscopic retrograde
      cholangiopancreatography in demonstrating bile leaks after laparoscopic
      cholecystectomy.
AB  - In two patients who had laparoscopic cholecystectomy, the postoperative course
      was complicated by continuous bilious drainage from the surgical drain in one and
      by jaundice in the other. In both patients, the findings of 99mTc-N-substituted
      2,6-dimethylphenyl carbamoylethyl iminodiacetic acid (HIDA) scanning were
      interpreted as clearly demonstrating a significant bile leak in one and the
      complete absence of bile passage from the liver to the intestines in the other.
      These findings could result from either spontaneous closure of the bile leak or
      false-positive HIDA scans. Subsequent endoscopic retrograde
      cholangiopancreatography (ERCP) showed the common bile duct and the cystic duct
      to be normal, without any evidence of bile leakage or any problem with drainage
      to the intestines. In all patients who have a positive 99mTc-HIDA scan, ERCP
      should be performed before deciding on further surgical intervention.

PMID- 9776292
TI  - 1-[Carbon-11]-glucose radiation dosimetry and distribution in human imaging
      studies.
AB  - 1-[Carbon-11]-D-glucose ([11C]-glucose) is an important imaging agent for PET
      studies that have been used to study the normal brain, encephalitis, epilepsy,
      manic-depressive disorder, schizophrenia and brain tumors. METHODS: Dosimetry
      estimates were calculated in subjects undergoing imaging studies to help define
      the radiation risk of [11C]-glucose PET imaging. Time-dependent radioactivity
      concentrations in normal tissues in 33 subjects after intravenous injection of
      [11C]-glucose were obtained by PET imaging. Radiation absorbed doses were
      calculated according to the procedures of the Medical Internal Radiation Dose
      (MIRD) committee along with the variation in dose based on the calculated
      standard deviation of activity distribution seen in the individual patients.
      RESULTS: Total body exposure was a median of 3.0 microGy/MBq in men and 3.8
      microGy/MBq in women. The effective dose equivalent was 3.8 microGy/ MBq in men
      and 4.8 microGy/MBq in women. The critical organs were those that typically take
      up the most glucose (brain, heart wall and liver). CONCLUSION: The organ doses
      reported here are small and comparable to those associated with other commonly
      performed nuclear medicine tests and indicate that potential radiation risks
      associated with this radiotracer are within generally accepted limits.

PMID- 9776293
TI  - Placental binding and transfer of radiopharmaceuticals: technetium-99m d, 1
      HMPAO.
AB  - Placental binding and transfer of 99mTc d, 1-hexamethyl propyleneamine oxime
      (HMPAO) was studied in vitro using human placenta and pregnant guinea pigs.
      MATERIALS AND METHODS: Five pieces of human placenta were incubated in 50 ml
      Earle's solution containing 1.85 MBq 99mTc d, 1-HMPAO. The percent binding of the
      tracer to the placenta per 1 ml standard solution was calculated. Pregnant guinea
      pigs representing first, second and third trimesters were each injected with 74
      MBq 99mTc d, 1-HMPAO through the jugular or femoral vein after sedation was
      induced with pentabarbital sodium. Static images were obtained, the guinea pigs
      were killed, and the fetuses were removed, weighed and imaged separately. The
      placentas, maternal and fetal brains, lungs, livers and kidneys also were
      removed, and the radioactivity was assayed in a dose calibrator for each organ.
      The percent radioactivity in each organ was calculated. RESULTS: The binding of
      99mTc d, 1-HMPAO to human placenta ranged from 2.95% +/- 1.5% to 5.82% +/- 0.3%
      per 1 ml standard solution. Both the binding of 99mTc d, 1-HMPAO to guinea pig
      placenta and its transfer to the fetus increased with gestational age. The
      percent binding ranged from 0.09% +/- 0.06% to 0.43% +/- 0.05%, whereas that of
      transfer to the fetus ranged from 0.05% +/- 0.03% to 2.19% +/- 0.64%. Of the
      amount transfered to the fetus, the order of accumulation in the fetal organs was
      liver > blood >> brain > lungs > kidneys > heart. CONCLUSION: Technetium-99m d, 1
      HMPAO binds to the placenta, and a minimal amount crosses the placental barrier
      and is transfered into the fetal circulation, mostly in the liver but a
      measurable amount is found in brain tissue.

PMID- 9776294
TI  - Biological properties of biotin-chelate conjugates for pretargeted diagnosis and
      therapy with the avidin/biotin system.
AB  - Three-step pretargeting increases target-to-background ratios in
      radioimmunodetection and can potentially decrease harmful radiation to normal
      tissues in radioimmunotherapy. We studied four biotin-chelate conjugates (BCCs)
      for use in the avidin/biotin pretargeting system. METHODS: Pharmacokinetics and
      biodistribution were studied in normal BALB/c (IAk-negative), normal C3H (IAk
      positive) and LS174T tumor-bearing BALB/c severe combined immunodeficient mice.
      Streptavidin alone and antibody-streptavidin conjugates [monoclonal antibody
      (MAb) 10-3.6 anti-IAk IgG2a] were used. Indium-111- or 88Y-BCCs were given alone
      intravenously; they were mixed with streptavidin or MAb-streptavidin conjugate
      and given intravenously; or streptavidin and MAb-streptavidin conjugate were
      pretargeted, and 2-3, 5 and 21 hr later, BCCs were injected intravenously.
      Samples were taken 2-3 hr after intravenous injection of labeled BCCs. RESULTS:
      Three of the four BCCs were rapidly excreted by the kidneys, with <2.5%/g in any
      organ or tumor at 2-3 hr. Gut excretion eliminated biotinyl-(S)-1-p
      aminobenzylethylenediaminetetraacetic acid (EDTA) for use in pretargeting. Ninety
      percent of BCCs were bound to circulating pretargeted streptavidin at 1-6 hr, and
      approximately 15% were bound to pretargeted streptavidin at 24 hr. Kidney uptakes
      were: preformed streptavidin-BCC given intravenously, approximately 80%/g (24
      hr); streptavidin pretargeted for 2-3 hr, approximately 60%/g; and streptavidin
      pretargeted for 5-21 hr, approximately 10%-20%/g. Kidney uptake was dose
      dependent: 0.2, 0.67 and 1.0 nmol of streptavidin pretargeted for 21 hr showed
      increasing concentrations (24 hr). Uptake of monoclonal anti-IAk-streptavidin-BCC
      complex into spleen (70% +/- 10%/g; p < 0.05) and lymph nodes (10% +/- 3.5%/g; p
      < 0.01) was higher in IAk-positive C3H mice than it was in IAk-negative control
      BALB/c mice, and it was much higher than that in streptavidin controls. No
      significant target uptake was seen with anti-IAk MAb-streptavidin pretargeted for
      3 or 20 hr. Kidney uptake approximately 20%/g, which was lower than that of
      streptavidin alone. CONCLUSION: Three biotinyl chelates bind the diagnostic and
      therapeutic radiometals 111In and 88Y (and, by analogy, 90Y) with the required in
      vivo stability and physiological properties for pretargeted diagnosis and
      therapy. Kidney uptake of streptavidin was decreased by conjugation to MAb.
      Failure of anti IAk MAb-streptavidin conjugate to bind BCC after pretargeting may
      be due to rapid internalization of MAb-streptavidin-IAk complex by the lymphocyte
      or to endogenous biotin. Either or both of these would make streptavidin
      unavailable to subsequent BCCs.

PMID- 9776295
TI  - Molecular imaging of atherosclerosis using a technetium-99m-labeled endothelin
      derivative.
AB  - Endothelins have been implicated in the pathogenesis of atherosclerosis and
      restenosis. The aim of this study was to characterize the potential of an
      endothelin derivative labeled with 99mTc for imaging experimental atherosclerosis
      in vivo. METHODS: Atherosclerosis was induced by balloon denudation of the
      infrarenal aorta in eight New Zealand white rabbits followed by a 6-wk period of
      a standard or 0.5% cholesterol diet in four animals, respectively. Another four
      rabbits served as controls, without balloon denudation and cholesterol feeding.
      Digital subtraction angiograms and planar whole-body scintigrams were obtained
      after intravenous injection of 74 MBq of the 99mTc-labeled endothelin derivative.
      The aorta was dissected for autoradiography, sudan-III staining, morphometry and
      immunohistology (anti-alpha-actin, RAM 11) 5 hr after injection. RESULTS: The
      lesions induced in the infrarenal aorta could be detected in vivo (whole-body
      scintigrams) in all treated animals only 15 min after injection of 99mTc
      endothelin derivative. Autoradiography of the excised aorta revealed good
      correlation of tracer accumulation and sudan-III-stained lesions. The ratio of
      accumulation between the induced lesions and untreated vessel wall was 6.8 +/-
      1.4 in the cholesterol-fed animals and 6.3 +/- 1.8 in the animals without
      cholesterol feeding. Accumulation of the endothelin derivative correlated with
      the number of smooth muscle cells (r = 0.924) but not with the amount of
      macrophages, the area or the maximum thickness of the plaques. CONCLUSION:
      Scintigraphic visualization of experimentally induced atherosclerosis in vivo is
      feasible using an endothelin derivative labeled with 99mTc.

PMID- 9776296
TI  - Renal depth estimates to improve the accuracy of glomerular filtration rate.
AB  - This study was performed to validate a computer implementation of the Gates'
      method for radionuclide glomerular filtration rate (RGFR) calculation. The
      accuracy of the original method was improved by replacing the Tonnesen formula
      that estimated renal depth with direct measurement from lateral views to
      calculate tissue attenuation correction. METHODS: Both the creatinine clearance
      test (CCT) and dynamic 99mTc-diethylenetriamine pentaacetic acid (DTPA) renal
      scintigraphy (DRS) were performed on 38 patients on the same day. RGFR was
      quantified from the attenuation corrected absolute DTPA uptake of the kidneys on
      DRS from 120-180 sec after injection. Attenuation correction was estimated using
      the lateral views of the kidneys taking in account the distance from the computed
      geometric center of the kidneys to the posterior body surface along a line
      vertical to the collimator surface. CCT and glomerular filtration rate estimates
      from DRS were compared by linear regression. RESULTS: RGFR estimates agreed well
      with CCT, yielding a correlation coefficient of 0.92 in 38 patients and 0.90 in a
      subgroup of 11 patients suffering from chronic renal failure. CONCLUSION: Present
      modifications improve RGFR accuracy to the precision range of blood sample based
      methods. This modified method requires little additional work and no extra cost
      in patients undergoing DRS. RGFR calculation may be advantageous in cases when 24
      hr urine collection for CCT cannot be obtained, and it should improve the
      accuracy of the captopril test.

PMID- 9776297
TI  - Statistical power analysis for PET studies in humans.
AB  - Although simple techniques have been established to determine statistical power
      when comparing, for example, the means of two groups of sampled data, the
      analysis is more complicated when establishing a trend in the data, such as with
      a linear regression. We present an approach to calculate the sample size
      necessary to reject the hypothesis that there is no trend in the data (slope is
      not different from zero) at a given level of statistical significance, given the
      intra- and inter-subject variability of the measurement. METHODS: We have derived
      analytically the distribution of the t statistic, for a given non-zero slope, and
      integrated this distribution to determine in what fraction of trials a real trend
      in the population would be missed. We illustrate our approach by re-examining the
      issue of an age-related impairment in presynaptic dopamine metabolism as measured
      by PET. RESULTS: We showed that the sample size necessary to determine whether 6
      18F-fluoro-L-dopa retention decreases with age depends critically on both the
      variability of the quantitative method used and on the magnitude of the expected
      change. CONCLUSION: The method we have illustrated is a simple statistical test
      that allows investigators to be certain that an experimental design has a
      sufficient sample size to demonstrate the effect under study.

PMID- 9776298
TI  - Technetium-99m-tetrofosmin SPECT imaging of lung lesions: a not-so-negative
      study.

PMID- 9776299
TI  - Technetium-99m-tetrofosmin scintigraphy, P-glycoprotein and lung cancer.

PMID- 9776300
TI  - Drug labeling changes.

PMID- 9776301
TI  - Apoptotic, non-apoptotic, and anti-apoptotic pathways of tumor necrosis factor
      signalling.
AB  - Early events in the signalling of tumor necrosis factor-receptor 1 (TNF-R1),
      which is the main TNF receptor on most cell types, have been clarified recently.
      A multimolecular signal transducing complex from which several pathways originate
      rapidly forms upon TNF-induced aggregation of the receptor. Although fully
      capable of transducing apoptotic signals, which depend on the adapter Fas
      associated death domain protein (FADD) and on the subsequent
      recruitment/activation of the apoptotic proteases, TNF-R1 usually does not kill
      cells; this is due to the induction of a complex cytoprotective response that
      requires TNF-receptor associated factor 2 (TRAF2), a signal transducer that
      couples TNF-R1 to both nuclear factor kappaB (NFkappaB)-dependent and NFkappaB
      independent transcriptional events implicated in induction of genes protecting
      from TNF cytotoxicity. Although absolutely required for cytoprotection, TNF
      receptor associated factor 2 is not sufficient to protect cells from TNF, thus
      suggesting that it may act in concert with additional TNF-R1 complex components.
      In this commentary, we will discuss some critical aspects of TNF-R1 signal
      transduction that are not fully understood: Why do cells not die before the
      protective protein synthesis has occurred? What are the mechanisms implicated in
      the termination of each TNF-R1-elicited response? Are there regulatory mechanisms
      capable of influencing the composition of the TNF-R1 complex and, consequently,
      the propagation of specific signals?

PMID- 9776302
TI  - Isoquinoline derivatives as endogenous neurotoxins in the aetiology of
      Parkinson's disease.
AB  - The cause of neurodegeneration in Parkinson's disease (PD) remains unknown.
      However, isoquinoline derivatives structurally related to the selective
      dopaminergic toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its
      active metabolite, 1-methyl-4-phenylpyridinim (MPP+), have emerged as candidate
      endogenous neurotoxins causing nigral cell death in Parkinson's disease.
      Isoquinoline derivatives are widely distributed in the environment, being present
      in many plants and foodstuffs, and readily cross the blood-brain barrier. These
      compounds occur naturally in human brain where they are synthesized by non
      enzymatic condensation of biogenic amines (e.g. catecholamines and
      phenylethylamine) with aldehydes, and are metabolized by cytochrome P450s and N
      methyltransferases. In addition, isoquinoline derivatives are oxidized by
      monoamine oxidases to produce isoquinolinium cations with the concomitant
      generation of reactive oxygen species. Neutral and quaternary isoquinoline
      derivatives accumulate in dopaminergic nerve terminals via the dopamine re-uptake
      system, for which they have moderate to poor affinity as substrates. Several
      isoquinoline derivatives are selective and more potent inhibitors of NADH
      ubiquinone reductase (complex I) and alpha-ketoglutarate dehydrogenase activity
      in mitochondrial fragments than MPP+, and lipophilicity appears to be important
      for complex I inhibition by isoquinoline derivatives. However, compared with
      MPP+, isoquinoline derivatives are selective but less potent inhibitors of NADH
      linked respiration in intact mitochondria, and this appears to be a consequence
      of their rate-limiting ability to cross mitochondrial membranes. Although both
      active and passive processes are involved in the accumulation of isoquinoline
      derivatives in mitochondria, inhibition of respiration is determined by steric
      rather than electrostatic properties. Compared with 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine or MPP+, isoquinoline derivatives show selective but
      relatively weak toxicity to dopamine-containing cells in culture and following
      systemic or intracerebral administration to experimental animals, which appears
      to be a consequence of poor sequestration of isoquinoline derivatives by
      mitochondria and by dopamine-containing neurones. In conclusion, the 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine-like cytotoxic characteristics of isoquinoline
      derivatives and the endogenous/environmental presence of these compounds make it
      conceivable that high concentrations of and/or prolonged exposure to isoquinoline
      derivatives might cause neurodegeneration and Parkinson's disease in humans.

PMID- 9776303
TI  - Influence of iron chelation on the antioxidant activity of flavonoids.
AB  - The antioxidant activity of flavonoids is believed to be caused by a combination
      of iron chelation and free radical scavenging activities. Several authors have
      attempted to separate the iron chelation and scavenging activity of flavonoids in
      order to study these processes individually. There are, however, several
      contradictions in the literature, and the outcome largely depends on the
      experimental conditions and the type of assay used. In order to investigate the
      contribution of iron chelation to the antioxidant activity of flavonoids, we
      determined the antioxidant activity of a group of flavonoids from several
      subclasses in an iron-independent (azobisamidinopropane, [ABAP]) lipid
      peroxidation (LPO) process and compared them with data from an iron-dependent
      (Fe2+/ascorbate) LPO process, which we determined earlier. These LPO data were
      compared with oxidation potentials, which were earlier found to have a good
      correlation with the scavenging activity of flavonoids. For most flavonoids, it
      was found that there was no difference between the LPO assays, indicating that
      iron chelation is either a constant factor among the flavonoids or is not
      significant in these types of assays. The IC50 values in the iron-independent LPO
      assay showed an excellent correlation with the oxidation potentials (Ep/2).
      Therefore, it can be concluded that for the majority of flavonoids tested, iron
      chelation does not play a role in the antioxidant activity in microsomal lipid
      peroxidation.

PMID- 9776304
TI  - Protective effects of the thiophosphate amifostine (WR 2721) and a lazaroid
      (U83836E) on lipid peroxidation in endothelial cells during
      hypoxia/reoxygenation.
AB  - Little is known about pharmacological interventions with thiophosphates or
      lazaroids in endothelial cells injured by hypoxia/reoxygenation with respect to
      membrane lipid peroxidation (LPO) caused by reactive oxygen species. Therefore, a
      cell line of bovine aortic endothelial cells was studied after 120-min hypoxia
      followed by 30-min reoxygenation, resulting in moderate and predominantly
      reversible injury (energy depression/cytosolic Ca2+-accumulation during hypoxia,
      which almost normalized during reoxygenation; membrane blebs, an increasing
      amount of lysosomes, vacuolization, lipofuscin formation, alterations in
      mitochondria size, some lyzed cells). 18.9 +/- 4.3% of the cells died. Radical
      induced LPO measured as malondialdehyde continuously increased to 2.18 +/- 0.17
      nmol/mg of protein after reoxygenation vs control (0.41 +/- 0.13, P < 0.05).
      Simultaneously, the content of 4-hydroxynonenal, a novel indicator of LPO,
      increased from 0.02 +/- 0.01 to 0.11 +/- 0.02 nmol/mg of protein (P < 0.01). The
      results support the assumption that reoxygenation injury is accompanied by an
      increase in membrane LPO, causing structural and functional disturbances in the
      monolayer. The thiophosphate WR 2721 [S-2-(3-aminopropylamino)
      ethylphosphorothioic acid] and the lazaroid U83836E [(-)-2-[[4-(2,6-di-1
      pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl] methyl]-3,4-dihydro-2,5,7,8
      tetramethyl-2H-1-benzopyran-6-ol (dihydrochloride)] were effective scavengers of
      .OH, being more efficient than trolox C (6-hydroxy-2,5,7,8-tetramethylchroman-2
      carbon acid) used as standard (EC50: 12, 5 and 15 microM, respectively, measured
      by electron spin resonance spectroscopy). One mM WR 2721, 10 microM U83836E, and
      5 microM trolox C reduced formation of malondialdehyde during
      hypoxia/reoxygenation to 53 +/- 7, 51 +/- 10 and 48 +/- 6%, respectively (P <
      0.05 each, versus control). In general, WR 2721 and U83836E prevent radical
      induced membrane LPO in a model of endothelial cells injured by
      hypoxia/reoxygenation. The use of these two agents is a new approach to protect
      the endothelium against oxidative stress.

PMID- 9776305
TI  - The inhibitory effect of cinchonine on human platelet aggregation due to blockade
      of calcium influx.
AB  - The Cinchona bark contains alkaloids like quinine, quinidine, cinchonine and
      cinchonidine. These agents are effective antimalarial drugs and have been used
      clinically in malaria caused by Plasmodium falciparum. Previous studies show that
      quinine and quinidine exert effects on cardiovascular system. This study was
      conducted to examine the effect of cinchonine on human platelet aggregation. The
      results show that cinchonine inhibited platelet aggregation mediated by platelet
      agonists, epinephrine (200 microM), ADP (4.3 microM), platelet activating factor
      (PAF; 800 nM) and collagen (638 nM) but had no effect on arachidonic acid (AA;
      0.75 mM). Cinchonine was most effective in inhibiting aggregation induced by
      platelet activating factor and epinephrine with IC50 values of 125 and 180 microM
      respectively, however, higher concentrations of cinchonine were required to
      inhibit aggregation mediated by ADP or collagen (IC50; 300 microM). Pretreatment
      of platelets with cinchonine inhibited aggregation caused by Ca2+ ionophore, A
      23187 (6 microM), in a dose-dependent manner (IC50; 300 microM) indicating an
      inhibitory effect on Ca2+-signaling cascade. This was supported by measuring
      [Ca2+]i in platelets loaded with Fura-2AM where cinchonine inhibited the rise in
      cytosolic Ca2+ mediated by A-23187 (6 microM) or collagen (638 nM). Results show
      that cinchonine (20 microM) also inhibited aggregation when platelets were
      pretreated with protein kinase C (PKC) activator, phorbol myristate acetate (PMA;
      0.1 microM) in combination with low doses of platelet activating factor (80 nM).
      Cinchonine, however, had no effect on AA-induced platelet aggregation and
      thromboxane A2 (TXA2) synthesis in platelets. These results suggest that
      antiplatelet effects of cinchonine are mediated mainly through inhibition of Ca2+
      influx and protein kinase C pathways in platelets.

PMID- 9776306
TI  - Glutathione-independent mechanism of apoptosis inhibition by curcumin in rat
      thymocytes.
AB  - Curcumin (CUR) is a natural yellow dye with antioxidant and scavenging properties
      present in Curcuma species. It is widely used as an anti-inflammatory, anti
      mutagenic and chemopreventive agent. In addition to its inhibitory effect on
      proliferation, CUR has recently been shown to block dexamethasone-induced
      programmed cell death (apoptosis) of rat thymocytes. Because cellular thiols seem
      to play a role in redox regulation of apoptosis, the mechanism of the anti
      apoptotic effect of CUR was studied by examining the levels of glutathione and
      acid-soluble sulfhydryl groups. CUR was shown to prevent the glutathione loss
      occurring in dexamethasone-treated thymocytes, enhancing intracellular
      glutathione content at 8 hr to 192% of that of nontreated cells. A 60% increase
      in acid-soluble sulfhydryl groups was also observed. In the presence of L
      buthionine S,R-sulfoximine (BSO, an inhibitor of glutathione synthesis),
      intracellular glutathione content of thymocytes treated with dexamethasone and
      CUR fell to 31% and that of the acid-soluble sulfhydryl groups to 23% of control
      after 8 hr. Unexpectedly, the electrophoretic and flow cytometric studies of DNA
      fragmentation demonstrated that apoptosis did not occur even after 20 hr of
      incubation with buthionine S,R-sulfoximine and dexamethasone, while control
      thymocytes and the cells treated only with buthionine S,R-sulfoximine showed DNA
      fragmentation at a level corresponding to spontaneous apoptosis. These results
      show that CUR treatment elevated the concentrations of glutathione and nonprotein
      sulfhydryl groups, thus preventing their decrease in apoptotic thymocytes.
      Coadministration of L-buthionine S,R-sulfoximine and CUR did not affect the anti
      apoptotic effect of CUR suggesting a glutathione-independent mechanism of cell
      protection.

PMID- 9776307
TI  - Agonist-induced down-regulation of the beta2-adrenoceptor and its mRNA in human
      mononuclear leukocytes.
AB  - Agonist-mediated regulation of beta2-adrenoceptors in mononuclear leukocytes has
      been examined at the protein but not at the mRNA level. In the present study,
      incubation of mononuclear leukocytes with the beta-agonist (-)-isoproterenol (10(
      6) M) for up to 42 hr led to a maximum decrease in both beta2-adrenoceptor mRNA
      concentration and total receptor number of ca. 56 and 70%, respectively. The
      decrease in the mRNA level, however, was slower than for the protein level. After
      4 hr of incubation with the beta-agonist, the protein level decreased to a
      minimum of 65% of the initial amount, while an incubation of 8 hr was necessary
      to reach a similar decrease in the level of mRNA (69% of the initial level).
      Measurements of mRNA stability revealed a reduction in the half-life of beta2
      adrenoceptor mRNA from 2.7 to 1.1 hr following 4 hr of incubation with (-)
      isoproterenol. Our data clearly demonstrate that treatment of human mononuclear
      leukocytes with (-)-isoproterenol induces a beta2-adrenoceptor down-regulation
      together with a slower time course of mRNA down-regulation which is partly due to
      a reduction of mRNA stability.

PMID- 9776308
TI  - Polyamine modulation of mitochondrial calcium transport. I. Stimulatory and
      inhibitory effects of aliphatic polyamines, aminoglucosides and other polyamine
      analogues on mitochondrial calcium uptake.
AB  - In this study, the regulation of mitochondrial Ca2+ transport by polyamines
      structurally related to spermine and by analogous polycationic compounds was
      characterized. Similar to spermine, a number of amino groups containing cationic
      compounds exerted a dual effect on Ca2+ transport of isolated rat liver
      mitochondria: a decrease in Ca2+ uptake velocity and an enhancement of Ca2+
      accumulation. In contrast to the effects of spermine and other aliphatic
      polyamines, however, the accumulation-enhancing effect of aminoglucosides, basic
      polypeptides, and metal-amine complexes turned into an inhibition of Ca2+
      accumulation at higher concentrations. Within groups of structurally related
      compounds, the potency to decrease Ca2+ uptake velocity and to enhance Ca2+
      accumulation correlated with the number of cationic charges. The presence of
      multiple, distributed cationic charges was a necessary, but not sufficient
      criterion for effects on mitochondrial Ca2+ transport, because cationic
      polyamines and basic oligopeptides which did not enhance mitochondrial Ca2+
      accumulation could be identified. Spermine was not able to antagonize the
      blocking of Ca2+ uptake by ruthenium red, but rather showed an apparent
      synergism, which can be explained as a displacement of membrane-bound Ca2+ by
      spermine. The aminoglucosides, gentamicin and neomycin, but not the inactive
      polyamine bis(hexamethylene)-triamine, inhibited the binding of spermine to
      intact mitochondria. Apparently, the binding of spermine, gentamicin, and a
      number of polyamine analogues to low-affinity binding sites at mitochondria,
      which have low, but distinct structural requirements and which may correspond to
      phospholipid headgroups, indirectly influences the activity state of the
      mitochondrial Ca2+ uniporter. The ability of aminoglucosides to displace spermine
      from the mitochondria and to inhibit mitochondrial Ca2+ accumulation may
      contribute to the mitochondrial lesions, which are known to occur early in the
      course of aminoglucoside-induced nephrotoxicity.

PMID- 9776309
TI  - Polyamine modulation of mitochondrial calcium transport. II. Inhibition of
      mitochondrial permeability transition by aliphatic polyamines but not by
      aminoglucosides.
AB  - In this study, the effects of polyamines and analogous compounds on mitochondrial
      permeability transition were characterized to distinguish between these effects
      and those on mitochondrial Ca2+ uptake, which are described in an accompanying
      report (Rustenbeck et al., Biochem Pharmacol 8: 977-985, 1998). When a
      transitional Ca2+ release from Ca2+-loaded mitochondria was induced by an acute
      increase in Ca2+ concentration in a cytosol-adapted incubation medium (Ca2+
      pulse), this process was inhibited, but not abolished by spermine in the
      concentration range of 0.4 to 20 mM. The aminoglucoside, gentamicin, and the
      basic polypeptide, poly-L-lysine, which like spermine are able to enhance
      mitochondrial Ca2+ accumulation (preceding paper), had no or only a minimal
      inhibitory effect, while the aliphatic polyamine, bis(hexamethylene)triamine,
      which is unable to enhance mitochondrial Ca2+ accumulation, achieved a complete
      inhibition at 4 mM. The conclusion that the Ca2+ efflux was due to opening of the
      permeability transition pore was supported by measurements of mitochondrial
      membrane potential, ATP production, and oxygen consumption. Mg2+, a known
      inhibitor of mitochondrial membrane permeability transition, did not mimic the
      effects of spermine on mitochondrial Ca2+ accumulation, while ADP, the main
      endogenous inhibitor, showed both effects. However, a combination of spermine and
      ADP was significantly more effective than ADP alone in restoring low Ca2+
      concentrations after a Ca2+ pulse. Two different groups of spermine binding sites
      were found at intact liver mitochondria, characterized by dissociation constants
      of 0.5 or 4.7 mM and maximal binding capacities of 4.6 or 19.7 nmol/mg of
      protein, respectively. In contrast to aminoglucosides, the aliphatic polyamine
      bis(hexamethylene)triamine did not displace spermine from mitochondrial binding
      sites. The total intracellular concentration of spermine in hepatocytes was
      measured to be ca. 450 microM and the free cytoplasmic concentration was
      estimated to be in the range of 10-100 microM. In conclusion, the enhancement of
      mitochondrial Ca2+ uptake by spermine is not an epiphenomenon of the inhibition
      of permeability transition. The physiological role of spermine appears to be that
      of an enhancer of mitochondrial Ca2+ accumulation rather than an inhibitor of
      permeability transition.

PMID- 9776310
TI  - Evidence for ryanodine receptors in Schistosoma mansoni.
AB  - The present study investigated the presence of ryanodine receptors in the
      trematode Schistosoma mansoni. [3H]Ryanodine specific binding sites were found in
      the four subcellular fractions of S. mansoni; however, more binding sites were
      recovered in the heterogeneous fraction P1 and the microsomal fraction P4, as was
      thapsigargin-sensitive (Ca2+-Mg2+)ATPase activity, marking the sarco/endoplasmic
      reticulum calcium ATPase (SERCA) pumps. This binding had an equilibrium
      dissociation constant (Kd) in the nanomolar range, an apparent maximal number of
      receptors (Bmax) of about 80 fmol/mg of protein, and was modulated by ions (Ca2+,
      Mg2+) and some pharmacological tools such as caffeine. Ryanodine was able to
      accelerate the rate of 45Ca2+ release from actively loaded vesicles, and also to
      induce a transient contraction of the whole worm. We conclude that ryanodine
      sensitive Ca2+ release channels are present in S. mansoni, with properties very
      similar to the ones present in higher animals.

PMID- 9776311
TI  - Isoform specificity of trimethylamine N-oxygenation by human flavin-containing
      monooxygenase (FMO) and P450 enzymes: selective catalysis by FMO3.
AB  - In the present study, we expressed human flavin-containing monooxygenase 1
      (FMO1), FMO3, FMO4t (truncated), and FMO5 in the baculovirus expression vector
      system at levels of 0.6 to 2.4 nmol FMO/mg of membrane protein. These four
      isoforms, as well as purified rabbit FMO2, and eleven heterologously expressed
      human P450 isoforms were examined for their capacity to metabolize trimethylamine
      (TMA) to its N-oxide (TMAO), using a new, specific HPLC method with radiochemical
      detection. Human FMO3 was by far the most active isoform, exhibiting a turnover
      number of 30 nmol TMAO/nmol FMO3/min at pH 7.4 and 0.5 mM TMA. None of the other
      monooxygenases formed TMAO at rates greater than 1 nmol/nmol FMO/min under these
      conditions. Human fetal liver, adult liver, kidney and intestine microsomes were
      screened for TMA oxidation, and only human adult liver microsomes provided
      substantial TMAO-formation (range 2.9 to 9.1 nmol TMAO/mg protein/min, N = 5).
      Kinetic studies of TMAO formation by recombinant human FMO3, employing three
      different analytical methods, resulted in a Km of 28 +/- 1 microM and a Vmax of
      36.3 +/- 5.7 nmol TMAO/nmol FMO3/min. The Km determined in human liver microsomes
      ranged from 13.0 to 54.8 microM. Therefore, at physiological pH, human FMO3 is a
      very specific and efficient TMA N-oxygenase, and is likely responsible for the
      metabolic clearance of TMA in vivo in humans. In addition, this specificity
      provides a good in vitro probe for the determination of FMO3-mediated activity in
      human tissues, by analyzing TMAO formation at pH 7.4 with TMA concentrations not
      higher than 0.5 mM.

PMID- 9776312
TI  - Combined expression of multidrug resistance protein (MRP) and glutathione S
      transferase P1-1 (GSTP1-1) in MCF7 cells and high level resistance to the
      cytotoxicities of ethacrynic acid but not oxazaphosphorines or cisplatin.
AB  - We tested the hypothesis that combined increased expression of human glutathione
      S-transferase P1-1 (GSTP1-1), an enzyme that catalyzes the conjugation with
      glutathione of several toxic electrophiles, and the glutathione-conjugate efflux
      pump, multidrug resistance protein (MRP), confers high level resistance to the
      cytotoxicities of anticancer and other drugs. To accomplish this, we developed
      MCF7 breast carcinoma cell derivatives that express high levels of GSTP1-1 and
      MRP, alone and in combination. Parental MCF7 cells, which express no GSTP1-1 and
      negligible MRP, served as control cells. We found that either MRP or GSTP1-1
      alone conferred significant resistance to ethacrynic acid cytotoxicity. Moreover,
      combined expression of GSTP1-1 and MRP conferred a high level of resistance to
      ethacrynic acid that was greater than resistance conferred by either protein
      alone. Increased MRP was also associated with modest resistance to the
      oxazaphosphorine compounds mafosfamide, 4-hydroxycyclophosphamide, and 4
      hydroperoxycyclophosphamide. However, coordinated expression of GSTP1-1 with MRP
      failed to augment this modest resistance. Similarly, GSTP1-1 had no effect on the
      sensitivities to cisplatin of MCF7 cells regardless of MRP expression. These
      results establish that coordinated expression of MRP and GSTP1-1 can confer high
      level resistance to the cytotoxicities of some drugs, including ethacrynic acid,
      but that such resistance is variable and does not apply to all toxic drugs that
      can potentially form glutathione conjugates in either spontaneous or GSTP1-1
      catalyzed reactions.

PMID- 9776313
TI  - SK&F 96365 (1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenylethyl]-1H-
      imidazole hydrochloride) stimulates phosphoinositide hydrolysis in human U373 MG
      astrocytoma cells.
AB  - SK&F 96365 (1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenylethyl]-1H-imi
      dazole hydrochloride) stimulated the accumulation of [3H]inositol monophosphates
      ([3H]IP1) in human U373 MG astrocytoma cells prelabelled with [3H]inositol (EC50
      15 +/- 1 microM, Hill coefficient 3.8 +/- 0.4). SK&F 96365-induced accumulation
      of [3H]IP1 increased linearly with time, but there was no initial rapid formation
      of [3H]IP3. SK&F 96365 also stimulated [3H]IP1 accumulation in human HeLa cells,
      but only to a small extent in slices of rat cerebral cortex and guinea-pig
      cerebellum. SK&F 96365-induced accumulation of [3H]IP1 in U373 MG cells increased
      as extracellular Ca2+ was increased from nominally zero to 4 mM, but there was no
      evidence that SK&F 96365 induced any marked entry of Ca2+ into cells; only an
      inhibition of store-refilling-induced Ca2+ entry was apparent. Further, the
      response to SK&F 96365 was additive with that to the Ca2+ ionophore ionomycin.
      Depolarization of the cells with raised K+ produced only a small stimulation of
      phosphoinositide hydrolysis. SK&F 96365 caused the release of Ca2+ from
      intracellular stores in U373 MG cells (EC50 26 +/- 14 microM), but thapsigargin
      induced only a small accumulation of [3H]IP1. Miconazole, another N-substituted
      imidazole, also stimulated [3H]IP1 accumulation in U373 cells.

PMID- 9776314
TI  - Antiproliferative and differentiating effects of benzodiazepine receptor ligands
      on B16 melanoma cells.
AB  - In this study, we evaluated the effect of several ligands active at the central
      type and peripheral-type benzodiazepine receptor (BzR) (clonazepam, diazepam,
      PK11195 and Ro5-4864) on the growth and differentiation of B16 melanoma cells.
      All tested BzR ligands were able to suppress proliferation of the cells at the
      micromolar range and in a concentration-dependent manner. However, agents
      selectively active at the peripheral-type BzR (PK11195 and Ro5-4864) exhibited
      more potent antiproliferative activity. In addition, the BzR ligands were
      demonstrated to affect the cell cycle by reducing the percent of cells in the S
      phase and increasing the percent in the G2/M phase. BzR ligands induced cellular
      phenotypic alterations, which have been previously shown to be associated with
      melanoma cell differentiation. These alterations included: marked morphological
      changes, enhancement of melanogenesis, lipid accumulation and increase in the
      activity of gamma glutamyl transpeptidase. All BzR ligands induced a marked
      reduction in the concentration of UTP and most of them did the same in GTP and
      CTP, while ATP levels were not significantly altered. In summary, BzR ligands
      (clonazepam, diazepam, PK11195 and Ro5-4864) were found to exert antitumor
      effects in B16 melanoma cells. These findings encourage further studies of a
      possible therapeutic potential of BzR ligands in treatment of melanoma.

PMID- 9776315
TI  - Phosphorylation of anticancer nucleoside analogs by human mitochondrial
      deoxyguanosine kinase.
AB  - The kinetic properties of recombinant human mitochondrial deoxyguanosine kinase
      (dGK, EC 2.7.1.113) for 2'-deoxyguanosine and the clinically important nucleoside
      analogs 2-chloro-2'-deoxyadenosine (CdA), 9-beta-D-arabinofuranosylguanine (araG)
      and 2',2',-difluorodeoxyguanosine (dFdG) were determined. The Michaelis-Menten
      kinetic parameters, comparing ATP and UTP as phosphate donors, demonstrated a
      marked increase in phosphorylation efficiency (VmaxKm) with UTP in comparison
      with ATP for both CdA and araG. The difluoro analog dFdG was an efficient
      substrate for recombinant dGK with an apparent Km of 16 microM with ATP as
      phosphate donor. We compared the kinetic properties of dGK with those of the
      related enzyme deoxycytidine kinase (dCK, EC 2.7.1.74). Although the purines 2'
      deoxyguanosine (dGuo) and 2'-deoxyadenosine are substrates for both dGK and dCK,
      only CdA among the purine nucleoside analogs tested was an efficient substrate
      for both dCK and dGK. In competition with dGuo, the most efficient analog for
      phosphorylation by dGK was araG, as indicated by a lower Ki value than for CdA
      and dFdG. Of the purine analogs tested as substrates for dCK, only CdA could
      compete with 2'-deoxycytidine (dCyd). No inhibition of dCK-mediated dCyd
      phosphorylation was found by either araG or dFdG. In crude cell extract of HeLa
      and Capan 2 cells, the major CdA phosphorylation was contributed by dCK, while
      most araG phosphorylation was a result of dGK activity. Our study with pure
      recombinant enzymes confirms that dGK is mainly responsible for araG and dFdG
      phosphorylation, whereas dCK is the most important enzyme for activation of CdA
      and 2',2'-difluorodeoxycytidine (dFdC).

PMID- 9776316
TI  - Stress-induced increase in urinary isatin excretion in rats: reversal by both
      dexamethasone and alpha-methyl-P-tyrosine.
AB  - The effects of acute food deprivation and acute cold exposure on 24-hr urinary
      isatin excretion in rats and a mechanism responsible for changes in urinary
      isatin excretion during stress were investigated. This is the first study to
      demonstrate by HPLC that urinary isatin excretion is increased by stress. Both
      types of stress induced a marked increase in urinary isatin excretion during the
      24 hr following the initiation of stress. Dexamethasone administration prevented
      the increase in urinary isatin excretion induced by both of the different types
      of stress. Furthermore, administration of either the benzodiazepine receptor
      agonist diazepam or the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine
      prevented the increase in urinary isatin excretion induced by acute food
      deprivation, whereas the dopamine-beta-hydroxylase inhibitor
      diethyldithiocarbamate proved ineffective. These observations suggest that during
      stress, activated catecholamine-synthesizing cells and corticotropin-releasing
      factor cells, both of which play central roles in stress responses, may be
      involved in total isatin production. Isatin may serve as an endogenously
      generated marker for some types of stress.

PMID- 9776317
TI  - Hormonal regulation of microsomal flavin-containing monooxygenase activity by sex
      steroids and growth hormone in co-cultured adult male rat hepatocytes.
AB  - To investigate the hormonal control of the expression of flavin-containing
      monooxygenase (FMO; EC 1.14.13.8) under defined in vitro conditions, adult male
      rat hepatocytes were isolated by collagenase perfusion and co-cultured with rat
      liver epithelial cells of primitive biliary origin. The direct effect of 17beta
      estradiol, testosterone, 5alpha-dihydrotestosterone (5alpha-DHT) and human growth
      hormone (hGH) on FMO activity was studied using this in vitro model. Optimal, non
      cytotoxic hormonal concentrations were determined by measuring the lactate
      dehydrogenase (LDH) index. In addition, the microsomal protein content of the
      cultured hepatocytes was determined as a function of culture time. The female sex
      hormone 17beta-estradiol caused a significant decrease in FMO as a function of
      culture time. After 14 days of exposure, FMO activity decreased by 56%. Neither
      of the male sex hormones or human growth hormone had an effect on FMO activity.
      These results in co-cultured male rat hepatocytes support in vivo observation
      that 17beta-estradiol is a potent hormone involved in the negative regulation of
      the expression of FMO in male rat liver.

PMID- 9776319
TI  - Interaction of cyclic GMP and cyclic AMP during neutrophil migration: involvement
      of phosphodiesterase type III.
AB  - In previous experiments, it was shown that migration of electropermeabilized
      human neutrophils induced by a combination of cGMP and cAMP markedly lower
      relative to that induced by cGMP or cAMP alone. However, when cGMP was replaced
      with 8-(para-chlorophenylthio-guanosine-3',5'-cyclic monophosphate (8-pCPT-cGMP),
      a metabolic stable analogue of cGMP which does not affect the activity of cGMP
      regulated phosphodiesterases (PDEs), migration in the presence of cAMP was
      enhanced in an additive way. To investigate the role of cyclic nucleotide
      breakdown during neutrophil migration in more detail, specific inhibitors of
      phosphodiesterase type III (PDE-III) (cGMP-inhibited) were used. Milrinone and
      cilostamide inhibited migration induced by an optimal concentration of cAMP. This
      revealed that inhibition of cAMP breakdown, by prolonging the action of an
      otherwise optimal concentration of cAMP, led to decreased migration, in
      accordance with the observation that the effect of cAMP on migration of
      electropermeabilized neutrophils was biphasic. Furthermore, it was found that a
      combination of 8-pCPT-cGMP and milrinone/cilostamide could substitute for cGMP in
      both activating cGMP-dependent protein kinase (8-pCPT-cGMP) and inhibiting PDE
      III (milrinone/cilostamide). In conclusion, evidence is presented that cGMP and
      cAMP could interact on the level of PDE-III during neutrophil migration.

PMID- 9776318
TI  - Structural and functional comparison of agents interfering with dihydroorotate,
      succinate and NADH oxidation of rat liver mitochondria.
AB  - Mitochondrially bound dihydroorotate dehydrogenase (EC 1.3.99.11) catalyses the
      fourth sequential step in the de novo synthesis of uridine monophosphate; this
      enzyme uses ubiquinone as the proximal and cytochrome oxidase as is the ultimate
      electron transfer system. Here, seven compounds with proven antiproliferative
      activity and in vitro antipyrimidine effects were investigated with isolated
      functional mitochondria of rat tissues in order to differentiate their anti
      dihydroorotate dehydrogenase potency versus putative effects on the respiratory
      chain enzymes. Ten microM of brequinar sodium, the leflunomide derivatives A77
      1726, [2-cyano-3-cyclopropyl-3-hydroxy-enoic acid (4-trifluoromethylphenyl)
      amide], MNA 279, (2-cyano-N-(4-cyanophenyl)-3-cyclopropyl-3-oxo-propanamide),
      MNA715 (2-cyano-3-hydroxy-N-(4-(trifluoromethyl)-phenyl-6-heptanamide), HR325 (2
      cyano-3-cyclopropyl-3-hydroxy-N-[3'-methyl-4'-(trifluoromethyl)phenyl ]
      propenamide), and the diazine toltrazuril completely inhibited the dihydroorotate
      induced oxygen consumption of liver mitochondria. Succinate and NADH oxidation
      were found to be influenced only at elevated drug concentration (100 microM),
      with the exception of HR325, 10 microM of which caused a 70% inhibition of NADH
      and 50% inhibition of succinate oxidation. This was comparable to the effects of
      toltrazuril, which caused an approximate 75% inhibition of NADH oxidation.
      Ciprofloxacin was shown here to have only marginal effects on the redox
      activities of the inner mitochondrial membrane. This differentiation of drug
      effects on mitochondrial functions will contribute to a better understanding of
      the in vivo pharmacological activity of these drugs, which are presently in
      clinical trials because of their immunosuppressive, cytostatic or anti-parasitic
      activity. A comparison of the influence of A77-1726, HR325, brequinar and 2,4
      dinitrophenol on energetically coupled rat liver mitochondria revealed only a
      weak uncoupling potential of A77-1726 and brequinar. In addition, a modeling
      study was raised to search for common spatial arrangements of functional groups
      essential for binding of inhibitors to dihydroorotate dehydrogenase. From the
      structural comparison of different metabolites and inhibitors of pyrimidine
      metabolism, a 6-point model was obtained by conformational analysis for the drugs
      tested on mitochondrial functions, pharmacophoric perception and mapping. We
      propose our model in combination with kinetic data for a rational design of
      highly specific inhibitors of dihydroorotate dehydrogenase.

PMID- 9776320
TI  - Effect of CI-930 [3-(2H)-pyridazinone-4,5-dihydro-6-[4-(1H-imidazolyl) phenyl]-5
      methyl-monohydrochloride] and rolipram on human coronary artery smooth muscle
      cell proliferation.
AB  - Experiments were conducted to determine how selective inhibitors of certain
      cyclic nucleotide phosphodiesterase (PDE) families, namely CI-930 (PDE3
      inhibitor; 3-(2H)-pyridazinone-4,5-dihydro-6-[4-(1H-imidazolyl) phenyl]-5-methyl
      monohydro chloride) and rolipram (PDE4 inhibitor), may affect human coronary
      artery smooth muscle cell (HCASMC) proliferation. CI-930- and rolipram
      inhibitable PDEs accounted for most of the cyclic AMP hydrolyzing activity in
      HCASMC. Twenty micromolar CI-930 and 20 microM rolipram used individually
      attenuated proliferation of HCASMC from some, but not all donors, as measured by
      flow cytometry. The simultaneous addition of 10 microM CI-930 plus 10 microM
      rolipram caused greater attenuation. This attenuation represented a reduction of
      the number of cells entering the S phase of the cell cycle and not merely a delay
      in cell cycle traverse. No statistically significant elevation of cyclic AMP was
      detected following the addition of either PDE inhibitor individually, but the
      combination produced significant elevations. It is concluded that CI-930- and
      rolipram-inhibitable PDE isozymes are expressed in HCASMC and that selective
      inhibitors of these isozymes can attenuate HCASMC proliferation. The data suggest
      that selective PDE inhibitors may prevent restenosis in patients following
      percutaneous transluminal coronary angioplasty because of their effect on HCASMC
      proliferation, and they may also be useful in retarding the progression of
      atherosclerosis in individuals at risk. PDE3 and PDE4 inhibitors in combination
      are more effective than the inhibitors used individually.

PMID- 9776321
TI  - No significant expression of CYP2E1 in rat liver stellate cells.
AB  - The putative role of the ethanol-inducible cytochrome P450(CYP)2E1 in stimulating
      collagen synthesis by rat liver stellate cells was studied. Analysis of carefully
      isolated stellate cells revealed that their content of immunoreactive CYP2E1
      protein and of CYP2E1 mRNA, as determined by reverse transcription, polymerase
      chain reaction (RT-PCR), was very low, i.e. only 0-4% of that in hepatocytes. We
      conclude that it is improbable that such low expression of CYP2E1 in stellate
      cells would have functional importance.

PMID- 9776322
TI  - Cysticercosis and epilepsy: a critical review.
AB  - Neurocysticercosis (NC) remains a major public health problem in developing and
      some developed countries. Currently, the best procedures for diagnosing NC are
      neuroimaging studies. Immunoserologic assays, such as enzyme-linked
      immunoelectrotransfer blot assay (EITB) or enzyme-linked immunosorbent assay
      (ELISA), detect antibodies against Taenia solium, or cysticercus. Consequently,
      they are useful in identifying a population at risk of contact with the parasite
      but do not necessarily indicate a systemic active infection. Most seropositive
      individuals are asymptomatic. No data from prospective studies concern the
      proportion of these individuals that will develop seizures or other neurologic
      symptoms. There is a discrepancy between the results of serologic assays and
      neuroimaging studies: >50% of those individuals with NC diagnosed by computed
      tomography (CT) scan test EITB negative. Pathophysiologic classification of NC
      into active, transitional, and inactive forms permits a good correlation between
      clinical manifestations and neuroimaging procedures and facilitates medical and
      surgical management and research. The most frequent clinical manifestations of NC
      are seizures. We assume that NC is the main cause of symptomatic epilepsy in
      developing countries; however, no case-control or cohort studies demonstrate this
      association. Most patients with NC with seizures have a good prognosis;
      nevertheless, further studies analyzing factors related to recurrence of seizures
      and possibilities of discontinuation of antiepileptic medications (AEDs) are
      needed. Regarding treatment of NC with antihelminthic drugs, no controlled
      clinical trials exist that establish specific indications, definitive doses, and
      duration of treatment. The most effective approach to taeniasis/cysticercosis
      infection is prevention. This should be a primary public health focus for
      developing countries. We critically review the available information regarding
      the epidemiology and diagnosis of human cysticercosis, the physiopathology and
      imaging correlation of the parasite in the central nervous system (CNS) of the
      host, the relation between seizures or epilepsy and NC, and the issues
      surrounding the treatment and prognosis of NC, including the use of
      antihelminthic therapy.

PMID- 9776323
TI  - Glucose utilization during interictal intervals in an epilepsy model induced by
      pilocarpine: a qualitative study.
AB  - PURPOSE: Interictal intervals in pilocarpine-induced chronic epilepsy are
      characterized by apparent normal electrographic activity and longer sleep periods
      or drowsiness or both. Sparse information exists concerning the neural network
      activity during these seizure-free intervals. In our research, a [14C]2-deoxy-D
      glucose (2DG) autoradiographic technique was used to investigate interictal
      changes in the metabolism of the epileptic rat brain. METHODS: Epileptic rats
      were monitored by video-EEG for approximately 120 days, with [14C]2DG injected
      after a seizure-free interval of > or = 24 h. RESULTS: Autoradiographic analysis
      revealed an increase in glucose utilization by several brain regions; the most
      consistent increase was found in the lateral posterior thalamic nucleus and
      pretectal region. CONCLUSIONS: These findings suggest that the lateral posterior
      thalamic nucleus and the pretectal region may be involved in cerebral circuits
      inhibiting epileptic activity during interictal intervals.

PMID- 9776324
TI  - Characterization of phenytoin-resistant kindled rats, a new model of drug
      resistant partial epilepsy: comparison of inbred strains.
AB  - PURPOSE: Previous work from our laboratory showed that amygdala-kindled Wistar
      outbred rats can be selected according to the increase of afterdischarge
      threshold (ADT) after phenytoin application. Animals that consistently do not
      respond to phenytoin (PHT) with an ADT increase (non-responders) are the first
      animal model of pharmacoresistant complex partial seizures. In this study, we
      determined the ability to respond to PHT in male kindled rats of different inbred
      strains. METHODS: The experiments were performed in fully kindled rats of five
      different inbred strains, Wistar-Kyoto, Lewis, Fischer 344, ACI, and Brown
      Norway. The response type of each rat was revealed by four consecutive PHT
      applications (75 mg/kg, i.p.) in fully kindled rats. RESULTS: PHT application
      resulted in plasma concentrations ranging from some 16 microg/ml in Lewis rats to
      35 microg/ml in Fischer 344 rats, and in slight ataxia, most strongly in Fischer
      344 rats. The rats of each strain did not show a homogeneous response to PHT. A
      significant increase of ADT was found after 86-97% of applications in Lewis,
      Wistar-Kyoto, and Fischer 344 rats. In contrast, Brown Norway rats responded in
      only 34% of experiments. This led to a considerable number of responders (i.e.,
      consistent ADT increase by >20%) in Fischer 344, Wistar-Kyoto, and Lewis rats.
      The only strain revealing nonresponders (i.e., consistent lack of ADT increase by
      >20% with PHT treatment) was Brown Norway. CONCLUSIONS: Inbred strains, although
      genetically more homogenous than outbred strains, differ in their response to
      PHT. Brown Norway rats can offer advantages for further detailed investigation of
      the resistance to PHT in the kindling model of complex partial seizures.

PMID- 9776325
TI  - Carbamazepine-induced release of serotonin from rat hippocampus in vitro.
AB  - PURPOSE: Carbamazepine is one of several antiepileptic drugs (AEDs) that release
      the inhibitory neurotransmitter serotonin as part of their pharmacodynamic action
      on brain neurons. We undertook this study to investigate the cellular processes
      by which carbamazepine (CBZ) releases serotonin from brain tissue. METHODS:
      Tissue slices were prepared from hippocampi of Sprague-Dawley rats. These
      hippocampal slices were preincubated in vitro in a buffer so that neurons within
      the slice would take up tritium-labeled serotonin. Subsequently the slices were
      superfused with buffer containing CBZ or other chemicals (or both) that increase
      the overflow of serotonin radioactivity. RESULTS: Carbamazepine produced a
      concentration-dependent (50, 125, 250, or 500 microM) increase in basal overflow
      of serotonin radioactivity from superfused rat hippocampal slices in vitro. In
      contrast, these concentrations did not alter potassium-stimulated release,
      suggesting that the CBZ-induced release does not depend on depolarization or
      exocytosis. Blockade of the neuronal membrane serotonin transporter by fluoxetine
      (1 microM) or citalopram (2 microM) did not alter overflow of serotonin
      radioactivity produced by 250 microM CBZ. p-chloramphetamine (10 microM) produced
      a substantial increase in overflow of serotonin radioactivity, and this effect
      appears to be antagonized by 250 microM CBZ. Uptake of [3H]-labeled serotonin
      into hippocampal synaptosomes was inhibited by CBZ with a median inhibitory
      concentration (IC50) of 511+/-33 microM and a Hill coefficient of 0.87+/-0.11,
      suggesting competitive inhibition of uptake by CBZ. CONCLUSIONS: We conclude that
      CBZ (a) releases serotonin from hippocampal slices independent of exocytosis and
      by a mechanism not involving the neuronal membrane serotonin transporter, and (b)
      at high enough concentration, blocks the neuronal serotonin transporter.

PMID- 9776326
TI  - Does short-term antiepileptic drug treatment in children result in cognitive or
      behavioral changes?
AB  - PURPOSE: To determine possible cognitive and behavioral effects of antiepileptic
      drug (AED) therapy by assessing children with newly diagnosed epilepsy before and
      after initiation of treatment. A comparison group of children with diabetes
      mellitus (DM) was included to control for the effects of practice, maturation,
      and chronic illness. METHODS: Baseline neuropsychological assessments were
      completed for children with epilepsy (n = 37) and children with DM (n = 26)
      recruited through outpatient clinics at a regional children's hospital. Children
      were reevaluated 6 months from baseline testing. At follow-up, children with
      epilepsy had therapeutic AED levels and controlled seizures. Statistical analysis
      included a between-group repeated measures ANCOVA with pretest scores serving as
      the covariate. RESULTS: Significant differences between groups were not found for
      any cognitive or behavioral factors, including attention (p < 0.24), immediate
      memory (p < 0.24), delayed memory (p < 0.10), complex motor speed (p < 0.19), or
      behavior problems (p < 0.89). CONCLUSIONS: Changes in performance on cognitive
      and behavioral measures were not different for children treated with AEDs and
      controls. Although adverse effects may be associated with prolonged treatment,
      results would not suggest adverse effects from AED monotherapy during the first 6
      months of therapy.

PMID- 9776327
TI  - Antiepileptic drug-related cognitive complaints in seizure-free children with
      epilepsy before and after drug discontinuation.
AB  - The cognitive complaints reported by children and their parents, as subjectively
      associated with antiepileptic drug (AED) treatment, were evaluated in seizure
      free children before and after drug discontinuation. The aim of the design was to
      isolate the cognitive side effects of AEDs from other factors, such as the effect
      of seizures. Our inventory explored the following areas: "alertness,"
      "concentration," "activation/ tiredness," "memory," "drowsiness," "depression,"
      "aggressiveness," and "hyperactivity," using a 5-point Likert scaling procedure.
      One hundred two eligible patients were selected, each matched with a healthy
      control and assessed when still on antiepileptic medication. All children were
      seizure free for at least 1 year. The medication was then discontinued gradually
      over a 3-month period. Four months after the children were completely medication
      free, a second assessment was carried out, but only in the 83 children who
      remained seizure free and in their matched controls. The results of the reports
      made by the children themselves did not show differences with the matched
      controls, and only showed improvement after drug discontinuation for complaints
      about "tiredness." Parents of the children with epilepsy reported significant
      improvement in all areas related to "alertness and activation" after
      discontinuation of the drugs. The finding that only a limited number of children
      have cognitive complaints, both when still on AEDs and after discontinuation, may
      be in line with the reports that the major factor contributing to quality of life
      is whether patients are seizure free or still have seizures. All patients in this
      study were seizure free for a period >1 year, which may have caused the favorable
      pattern of response in our patient group.

PMID- 9776328
TI  - Individual memory change after anterior temporal lobectomy: a base rate analysis
      using regression-based outcome methodology.
AB  - PURPOSE: To characterize patterns of base rate change on measures of verbal and
      visual memory after anterior temporal lobectomy (ATL) using a newly developed
      regression-based outcome methodology that accounts for effects of practice and
      regression towards the mean, and to comment on the predictive utility of baseline
      memory measures on postoperative memory outcome. METHODS: Memory change was
      operationalized using regression-based change norms in a group of left (n = 53)
      and right (n = 48) ATL patients. All patients were administered tests of episodic
      verbal (prose recall, list learning) and visual (figure reproduction) memory, and
      semantic memory before and after ATL. RESULTS: ATL patients displayed a wide
      range of memory outcome across verbal and visual memory domains. Significant
      performance declines were noted for 25-50% of left ATL patients on verbal
      semantic and episodic memory tasks, while one-third of right ATL patients
      displayed significant declines in immediate and delayed episodic prose recall.
      Significant performance improvement was noted in an additional one-third of right
      ATL patients on delayed prose recall. Base rate change was similar between the
      two ATL groups across immediate and delayed visual memory. Approximately one
      fourth of all patients displayed clinically meaningful losses on the visual
      memory task following surgery. Robust relationships between preoperative memory
      measures and nonstandardized change scores were attenuated or reversed using
      standardized memory outcome techniques. CONCLUSIONS: Our results demonstrated
      substantial group variability in memory outcome for ATL patients. These results
      extend previous research by incorporating known effects of practice and
      regression to the mean when addressing meaningful neuropsychological change
      following epilepsy surgery. Our findings also suggest that future
      neuropsychological outcome studies should take steps towards controlling for
      regression-to-the-mean before drawing predictive conclusions.

PMID- 9776329
TI  - Antiepileptic drug use in nursing home residents: effect of age, gender, and
      comedication on patterns of use.
AB  - PURPOSE: Examine antiepileptic drug (AED) use in nursing homes by age, gender,
      and use of comedication that can interact with AEDs. METHODS: Two point
      prevalence evaluations of AED use from computerized medical records of nursing
      home residents throughout the United States (set 1, 43,757; set 2, 41,386) 65
      years and older serviced by PHARMERICA. RESULTS: 10.5% of residents received an
      AED. Of the age group 65-84 years, 15 % received an AED compared with 6.1% of
      those 85 years or older (p < 0.001). Gender differences were present; 13.4% of
      the male residents and 9.4% of the female residents were treated with an AED (p <
      0.001). The most frequently prescribed AEDs were phenytoin, carbamazepine,
      clonazepam, or phenobarbital. The average number of routine medications taken by
      AED recipients was 5.6, greater than the average of 4.6 for other residents.
      CONCLUSIONS: AEDs are extensively prescribed for elderly nursing home residents.
      Men and persons aged 65-85 years were more likely to receive AEDs than were women
      or those older than 85 years. AED recipients receive more routine medications
      than do other residents, including co-medications that alter hepatic metabolism
      and clinical response. The reasons for age and gender differences are unclear and
      require further study.

PMID- 9776330
TI  - Neuropsychological outcomes in randomized controlled trials of antiepileptic
      drugs: a systematic review of methodology and reporting standards.
AB  - PURPOSE: To systematically review the methodology and use of neuropsychological
      tests in randomized controlled trials (RCTs) of antiepileptic drugs (AEDs) in
      patients with epilepsy. METHODS: Trial reports were found by searching Medline
      1966-1996 and searching through journals by hand. Inclusion and exclusion
      criteria were applied, and methodological and neuropsychological test data was
      extracted by using a proforma. RESULTS: 43 reports met our inclusion criteria,
      representing 40 RCTs. as three RCTs had generated two reports. Twenty-two were
      actively controlled, and 18 were placebo-controlled studies. Reporting of basic
      methods such as randomization method was poor. There has been no uniform approach
      to the use of neuropsychological tests, and a total of 87 has been used. The
      Stroop Colour Word Test and the Finger Tapping Test were most commonly used, at
      13 times each, but were not used or reported in a uniform manner. CONCLUSIONS:
      Poor reporting of methods and the use of a plethora of neuropsychological tests
      create great difficulties for anyone wishing to make sense of currently available
      data. If we are better to understand the neuropsychological effects of AEDs, a
      more rational approach is needed, for which recommendations are made.

PMID- 9776331
TI  - A stereoelectroencephalographic (SEEG) study of light-induced mesiotemporal
      epileptic seizures.
AB  - PURPOSE: This study explored the mechanism of light-induced complex partial
      seizures by using ictal intracerebral recordings in a patient with refractory
      epilepsy of the right temporal lobe. METHODS: Presurgical evaluation of this
      patient was realized by means of video-EEG recordings, WADA test, magnetic
      resonance imaging (MRI), F18-deoxyglucose and C11-flumazenil positron emission
      tomography (PET) interictal neuroimaging data, and stereoelectroencephalographic
      (SEEG) ictal recordings. RESULTS: SEEG investigations demonstrated the right
      mesiotemporal origin of all the patient's seizures. This result was confirmed by
      a successful right temporal lobectomy. Moreover, SEEG recordings revealed a
      frequent interictal spiking activity in the right occipital visual cortex that
      was undetectable on scalp recordings. However, the occipital cortex was not
      involved at the onset of mesiotemporal ictal discharges and was not
      hyperresponsive to focal electrical stimulation. CONCLUSIONS: This study shows
      that, in spite of interictal occipital spiking, the photosensitivity of
      mesiotemporal seizures can be observed in both the absence of occipital cortex
      involvement during ictal discharges and demonstrable hyperexcitability of the
      occipital cortex to light or direct electrical stimulation.

PMID- 9776332
TI  - Clonidine- and methohexital-induced epileptiform discharges detected by
      magnetoencephalography (MEG) in patients with localization-related epilepsies.
AB  - PURPOSE: During presurgical evaluation, 14 patients with medically intractable
      focal epilepsies underwent magnetoencephalographic (MEG) recordings to localize
      the epileptogenic focus. To increase the number of epileptiform discharges
      required for MEG analysis, methohexital a short-acting barbiturate that is known
      to activate epileptiform activity, was used. Additionally, we investigated the
      spike-provoking properties of clonidine in comparison to methohexital. METHODS:
      After oral premedication with clonidine, short-lasting anesthesia was provided by
      intravenously administered methohexital. The number and location of epileptiform
      MEG discharges were assessed after clonidine premedication and during
      methohexital anesthesia. Results were compared with baseline MEG recordings.
      RESULTS: Methohexital increased the frequency of focal epileptiform discharges in
      eight of 13 patients (one of the 14 patients did not receive methohexital after
      premedication with clonidine). Additionally, premedication with clonidine was
      found to increase focal epileptiform discharges in nine of 14 patients. When
      compared with baseline MEG recordings, recordings after treatment with both
      clonidine premedication and methohexital anesthesia showed a significant increase
      in the total number of epileptiform signals and the number of spikes contributing
      to MEG source localizations. CONCLUSIONS: This study confirms the selective
      proconvulsant effects of methohexital on the epileptogenic focus as suggested
      previously by EEG and electrocorticogram (ECoG) investigations. Additionally, our
      data establish for the first time that clonidine increases epileptiform activity
      in patients with seizure disorders. These results indicate that clonidine is
      suited as an activating agent for the localization of epileptogenic foci by means
      of MEG. This effect of clonidine on specific epileptic activity also indicates
      that clonidine should be used with caution as an antihypertensive drug in
      patients with seizure disorders.

PMID- 9776333
TI  - Chronic stimulation of the left vagal nerve in children: effect on swallowing.
AB  - PURPOSE: To learn whether stimulation of the left vagal nerve would influence
      swallowing. METHODS: Eight children receiving intermittent left vagal nerve
      stimulation (VNS) for their pharmacoresistant epilepsy underwent barium swallow
      studies with their generators off, on, and at maximally tolerated settings.
      RESULTS: Laryngeal penetration of barium was present in three patients without
      stimulation, and was caused by VNS in one other patient. Aspiration never
      occurred. CONCLUSIONS: Stimulation of the left vagal nerve under conditions used
      to treat epilepsy does not cause aspiration.

PMID- 9776334
TI  - Carbamazepine intoxication with negative myoclonus after the addition of
      clobazam.
AB  - We report a case a carbamazepine (CBZ) intoxication with negative myoclonus that
      occurred 4 weeks after clobazam (CLB) had been added to a stable regimen of CBZ
      and topiramate (TPM). Both CBZ and CBZ-epoxide (CBZ-E) blood levels were
      elevated, and the symptoms resolved quickly when CBZ dosage was reduced and CLB
      discontinued. CLB was reintroduced a year later with the patient's consent, and
      the time course of the interaction was studied: CBZ and CBZ-E levels increased
      slowly over 12 days. The interaction is thus probably related to the progressive
      increase in Nor-CLB.

PMID- 9776335
TI  - Ictal oroalimentary automatisms with preserved consciousness: implications for
      the pathophysiology of automatisms and relevance to the international
      classification of seizures.
AB  - A patient showing seizures presenting ictal automatisms with preserved
      consciousness is reported. A 30-year-old, right-handed man with normal
      development and without family history of epilepsy was referred for surgical
      treatment of epilepsy. At 15 he began to have seizures, starting with an
      epigastric aura, occasionally developing automatisms (lip-smacking, chewing),
      sometimes followed by tonic-clonic convulsions. At the time of referral, he
      averaged six convulsive seizures per year and one nonconvulsive per week. His
      sleep EEG showed sharpened slow activity over the right anterior quadrant
      magnetic resonance imaging (MRI) showed a benign lesion in the mesial aspect of
      the right occipital lobe. Simultaneous video monitoring and intracranial EEG with
      subdural strips recording from the right temporal and occipital lobes was
      undertaken. During one seizure, he had pronounced oroalimentary automatisms while
      holding a conversation with a technician, answering her questions, and explaining
      details of his seizures. Memory of this event was preserved. At seizure onset,
      spike activity was seen at the mesial occipital strips. At midseizure, high
      voltage sharpened delta was seen throughout the right hemisphere. Left-sided
      scalp electrodes remained relatively uninvolved. The lesion, a dysembryoplastic
      neuroepithelial tumour was removed. Surgery was followed by abolition of seizures
      described. Because it is agreed that complex partial seizures require impaired
      consciousness, a history of automatisms with retained consciousness usually
      suggests nonepileptic attacks. This case suggests that automatisms in epileptic
      seizures can take place with minimal loss of consciousness, particularly if there
      is widespread but unilateral involvement. The need for a revision of the
      International Classification is suggested.

PMID- 9776336
TI  - Inhibition of the gap junctional component of endothelium-dependent relaxations
      in rabbit iliac artery by 18-alpha glycyrrhetinic acid.
AB  - The gap junction inhibitor 18-alpha-glycyrrhetinic acid (alpha-GA, 100 microM)
      attenuated endothelium-dependent relaxations to acetylcholine and cyclopiazonic
      acid by approximately 20% in rings of pre-constricted rabbit iliac artery. The
      nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 300
      microM) inhibited relaxations to both agents by approximately 65% and these were
      further attenuated by alpha-GA to < 10% of control. In endothelium-denuded
      preparations, relaxations to sodium nitroprusside were not affected by alpha-GA.
      Heterocellular gap junctional communication may therefore account for nitric
      oxide-independent relaxations evoked both by receptor-dependent and -independent
      mechanisms in rabbit iliac artery.

PMID- 9776337
TI  - Somatostatin displayed on filamentous phage as a receptor-specific agonist.
AB  - 1. In search of methods to identify bio-active ligands specific for G protein
      coupled receptors with seven transmembrane spanning regions, we have developed a
      filamentous phage-based selection and functional screening method. 2. First,
      methods for panning peptide phage on cells were established, using the hormone
      somatostatin as a model. Somatostatin was displayed on the surface of filamentous
      phage by cloning into phage(mid) vectors and fusion to either pIII or pVIII viral
      coat proteins. Peptide displaying phage bound to a polyclonal anti-somatostatin
      serum, and, more importantly, to several somatostatin receptor subtypes (Sst)
      expressed on transfected CHO-K1 cells, in a pattern which was dependent on the
      used display method. Binding was competed with somatostatin, with an IC50 in the
      nanomolar range. The phage were specifically enriched by panning on cells,
      establishing conditions for cell selections of phage libraries. 3. Binding of
      somatostatin displaying phage to sst2 on a reporter cell line, in which binding
      of natural ligand reduces secretion of alkaline phosphatase (via a cyclic AMP
      responsive element sensitive promoter), proved that the phage particles act as
      receptor-specific agonists. Less than 100 phage particles per cell were required
      for this activity, which is approximately 1000 fold less than soluble
      somatostatin, suggesting that phage binding interferes with normal receptor
      desensitization and/or recycling. 4. The combination of biopanning of phage
      libraries on cells with functional screening of phage particles for receptor
      triggering activity, may be used to select novel, bio-active ligands from phage
      libraries of random peptides, antibody fragments, or libraries based on the
      natural receptor ligand.

PMID- 9776338
TI  - ATP-sensitive K+ channels in smooth muscle cells of guinea-pig mesenteric
      lymphatics: role in nitric oxide and beta-adrenoceptor agonist-induced
      hyperpolarizations.
AB  - 1. Intracellular microelectrode recordings were performed to investigate the
      membrane K+ conductances involved in smooth muscle hyperpolarization of lymphatic
      vessels in the guinea-pig mesentery. 2. Nitric oxide (NO), released either by the
      endothelium after acetylcholine (ACh; 10 microM) stimulation or by sodium
      nitroprusside (SNP; 50-100 microM), hyperpolarized lymphatic smooth muscle. These
      responses were inhibited with the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazole
      [4,3-a]quinoxalin-1-one (ODQ, 10 microM). 3. ACh and SNP-induced
      hyperpolarizations were inhibited (by about 90%) upon application of the ATP
      sensitive K+(K(ATP)) channel blocker, glibenclamide (10 microM), or with 4
      aminopyridine (2.5 mM), but were not affected by the Ca2+-activated K+ channels
      blocker, penitrem A (100 nM). 4. Hyperpolarization caused by the K+ channel
      opener, cromakalim (0.1-10 microM), isoprenaline (0.1 microM) or forskolin (0.5
      microM) were all significantly blocked by glibenclamide. 5. Hyperpolarization
      evoked by ACh and SNP were inhibited with N-[2-(p-bromociannamylamino)-ethyl]-5
      isoquinolinesulfonamide-dich loride (H89, 10 microM), suggesting the involvement
      of cyclic AMP dependent protein kinase (PKA). 6. These results suggest that
      K(ATP) channels play a central role in lymphatic smooth muscle hyperpolarization
      evoked by a NO-induced increase in cyclic GMP synthesis, as well as by beta
      adrenoceptor-mediated production of cyclic AMP. Interestingly, both pathways lead
      to K(ATP) channels opening through the activation of PKA.

PMID- 9776339
TI  - Investigation on the mechanisms involved in the central protective effect of
      amylin on gastric ulcers in rats.
AB  - 1. The mechanisms involved in the protective effect of amylin (administered into
      the brain ventricle, i.c.v.) on gastric ulcers induced by the oral administration
      of ethanol 50% (EtOH, 2 ml/rat) or indomethacin (indomethacin, 20 mg kg(-1), at a
      dosing volume of 5 ml) were investigated in rats. 2. The possible involvement of
      endogenous nitric oxide (NO) in the beneficial effect of amylin against EtOH
      induced ulcers was examined. The inhibitor of NO-synthesis, NG-nitro-L-arginine
      methyl ester (L-NAME, 70 mg kg(-1), s.c.) was injected 30 min before amylin (2.2
      microg/rat, i.c.v.) followed by EtOH after a further 30 min. Rats were sacrificed
      1 h after EtOH. L-NAME completely removed the protective effect of amylin. 3. The
      interaction between amylin and gastric nonprotein sulfhydryl groups was studied.
      The rats were treated with N-ethyl-maleimide (NEM, 25 mg kg(-1), s.c.) 30 min
      before amylin (2.2 microg/rat, i.c.v.) followed by EtOH 30 min after or by
      indomethacin 5 min after amylin. Rats were sacrificed 1 h or 6 h respectively
      after EtOH or indomethacin. NEM counteracted the protective effect of amylin
      against EtOH-induced ulcers but not against those provoked by indomethacin. 4. To
      determine whether amylin was able to promote ulcer healing, the peptide was
      injected 5 min after EtOH or 1 h after indomethacin. In the case of EtOH, the
      beneficial effect of amylin was lost whereas it was still effective on
      indomethacin-induced ulcers. 5. The results indicate that: the mechanisms
      involved in the antiulcer effects of amylin are different in these two types of
      gastric lesions probably because of the different etiopathology of various types
      of ulcers. Endogenous NO and nonprotein sulfhydryl groups are involved in the
      mucosal protective effects of amylin on EtOH and not on indomethacin-induced
      ulcers. Furthermore the effectiveness of amylin against indomethacin-induced
      lesions when administered after the ulcerogenic process has started suggests that
      amylin is involved not only in the protection but also in the healing mechanisms
      in this type of ulcer.

PMID- 9776340
TI  - Antithrombotic activity of a monoclonal antibody inducing the substrate form of
      plasminogen activator inhibitor type 1 in rat models of venous and arterial
      thrombosis.
AB  - 1. Elevated plasminogen activator inhibitor 1 (PAI-1) is a risk factor for
      thrombosis, and inhibitors of the interaction between PAI-1 and tissue
      plasminogen activator (t-PA) have antithrombotic and prothrombolytic activity in
      animals. We describe the antithrombotic effects in the rat of a monoclonal
      antibody (MA33H1) which converts PAI-1 to a non-inhibitory substrate. 2. The
      activity of MA33H1 against rat PAI-1 was confirmed using two-chain t-PA and a
      chromogenic substrate. MA33H1 was evaluated in rat venous (thromboplastin +
      stasis in the abdominal vena cava) and arterial (electric current applied to a
      carotid artery) thrombosis models. The effects on tail-transection bleeding time
      were studied. 3. MA33H1 at 100 ng ml(-1) inhibited both human (44.1%) and rat PAI
      1 (49.7%). This effect was concentration-dependent. Its effect on human PAI-1 was
      not significantly inhibited by 1 microg ml(-1) fibrin or a approximately 7 fold
      molar excess of vitronectin (1 nM). Inhibition of rat PAI-1 was unchanged by
      fibrin, but vitronectin reduced inhibition from 0.5 nM. 4. In the venous
      thrombosis model, MA33H1 significantly reduced thrombus weights by 38 and 58.6%
      at 50 and 100 microg kg(-1) min(-1) i.v. respectively. This effect was inhibited
      by tranexamic acid. In the arterial model, MA33H1 significantly increased the
      delay to occlusive thrombus formation by 58 and 142% at 50 and 100 microg kg(-1)
      min(-1) i.v., and did not affect bleeding time at 300 microg kg(-1) min(-1) i.v.
      5. Thus, a monoclonal antibody which transforms PAI-1 to a t-PA substrate
      prevents thrombus formation in the rat with no effect on bleeding time at a
      higher dose.

PMID- 9776341
TI  - Influence of various combinations of specific antibody dose and affinity on
      tissue imipramine redistribution.
AB  - 1. This study was designed to evaluate the distribution kinetics of imipramine
      (Imip) in the brain and the main peripheral organs (heart, kidney, liver and
      lung) of rats, and to establish the relationship between the redistribution of
      Imip from these tissues and the immunoreactive capacity (dose and affinity) of
      anti-TCA IgG. 2. [3H]-Imip (1 nmol kg(-1) body weight) was injected intravenously
      6 min before the i.v. injection of antibodies. At this time, the concentrations
      of Imip and its main metabolites in plasma were determined. The radioactivity
      measured corresponded to 91.7% Imip, indicating that the pharmacokinetics
      reflected essentially Imip. Plasma and tissue Imip contents were measured over
      the interval 1 to 90 min in control and in treated rats. The antibodies used were
      a murine monoclonal IgG1 (Ka=3.8 10(7) M(-1)) at an IgG1/Imip molar ratio of 1000
      (IgG1 1000), and a sheep polyclonal IgG (TAb, Ka=1.3 10(10) M(-1)) at IgG/ Imip
      molar ratios of 1, 10 and 100 (TAb1, TAb10 and TAb100). 3. The anti-TCA IgG
      increased the plasma [3H]-Imip concentrations: the AUC1-->60 min for [3H]-Imip
      were 4 (IgG1 1000), 9 (TAb1), 33.9 (TAb10) and 41.4 (TAb100) times higher in the
      treated groups than in the controls. The opposite effect occurred in the brain,
      heart and lungs, with large, rapid decreases in Imip. The increase in plasma Imip
      and the decrease in tissue Imip depended on the immunoreactive capacity (NKa) of
      the antibody, where N=molar concentration of IgG binding sites and Ka=IgG
      affinity constant. Maximal plasma and tissue redistribution occurred when
      NKa=33.8 x 10(4). 4. Imip redistribution can be controlled using various doses or
      affinities of specific antibodies, and the resulting rapid, extensive Imip
      redistribution from the main target organs could be very promising for TCA
      detoxification.

PMID- 9776342
TI  - Potent vasodilatory with minor cardiodepressant actions of mibefradil in human
      cardiac tissue.
AB  - 1. The present study compared the cardiovascular effects of mibefradil (MIB), a
      novel Ca2+-channel antagonist with high selectivity for T-type Ca2+-channels to
      the effect of the L-type Ca2+-channel-antagonists nifedipine (NIF) and diltiazem
      (DIL) in left ventricular myocardium and coronary arteries of hearts obtained
      from patients suffering from dilated cardiomyopathy (NYHA IV). Right atrial
      myocardium from patients undergoing aortocoronary bypass surgery without signs of
      cardiac failure was studied as well. 2. NIF and DIL (100 micromol l(-1))
      completely depressed force of contraction (FOC) in electrically driven left
      ventricular myocardium (NIF 6.5+/-1.4% and DIL 7.1+/-1.2% of control), whereas a
      similar concentration of MIB only reduced force of contraction to 55.1+/-4.0% of
      the basal FOC. The negative inotropic potency as measured by the concentration
      needed to reduce basal FOC for 25% was NIF (0.0095 micromol l(-1))>DIL (0.041
      micromol l(-1))>MIB (9.47 micromol l(-1)). 3. All three Ca2+-channel antagonists
      were more potent in human atrial compared to human left ventricular myocardium to
      reduce FOC. 4. The rank order of Ca+-antagonistic moiety as measured by the
      decrease of the intracellular Ca2+-transient (fura-2 ratio method) was
      NIF>DIL>MIB. 5. All Ca2+-channel antagonists completely relaxed human coronary
      arteries (% of papaverine effect: MIB 81.7+/-5.5%, DIL 91.3+/-0.9%, NIF 96.4+/
      3.7%) precontracted with PGF2alpha (0.3 micromol l(-1)). The rank order of
      vasodilatory potency was NIF (EC50; 0.02 micromol l(-1))>DIL (0.13 micromol l(
      1))>MIB (2.05 micromol l(-1)). 6. The vasoselectivity measured by the ratio of
      the concentration needed to achieve a 25% decrease in force and the concentration
      needed for 25% vasodilatation was 316 for MIB, 1.5 for NIF and 1.0 for DIL. 7.
      The present study provides evidence that blockade of T-type Ca2+-channels (e.g.
      mibefradil) results in potent vasodilatory properties with only minor
      cardiodepressant effects.

PMID- 9776343
TI  - The transport of the anti-HIV drug, 2',3'-didehydro-3'-deoxythymidine (D4T),
      across the blood-brain and blood-cerebrospinal fluid barriers.
AB  - 1. The brain is a site of infection, viral replication and sanctuary for HIV-1.
      The treatment of HIV-1 infection therefore requires that an effective agent be
      delivered to the brain. 2',3'-Didehydro-3'-deoxythymidine (D4T) is a nucleoside
      analogue which has been shown to have beneficial clinical effects in the
      treatment of HIV infection. However, although D4T has been detected in human CSF,
      the ability of this drug to cross both the blood-brain and blood-cerebrospinal
      fluid (CSF) barriers and gain entrance into the brain tissue is not known. 2.
      This study examined the CNS entry of D4T by means of the bilateral vascular brain
      perfusion technique in the anaesthetized guinea-pig. 3. The results indicated
      that [3H]-D4T had a limited ability to cross the blood-brain barrier (BBB), which
      was not significantly greater than D-[14C]-mannitol (a slowly penetrating marker
      molecule). Although D4T was found to cross the blood-CSF barrier, the presence of
      D4T in the CSF did not reflect levels of the drug in the brain tissue. 4. These
      results can be related to the measured low lipophilicity of D4T, the higher
      paracellular permeability characteristics of the choroid plexus (blood-CSF
      barrier) compared to the BBB, and the sink action nature of the CSF to the brain
      tissue. 5. In conclusion, these animal studies suggest that D4T may only
      penetrate the brain tissue to a limited extent and consideration should be given
      to these findings in the clinical situation.

PMID- 9776344
TI  - Endothelin-1 stimulates sodium-dependent calcium efflux from bovine adrenal
      chromaffin cells in culture.
AB  - 1. The effect of endothelin (ET)-1 on Ca2+ efflux from cultured bovine adrenal
      chromaffin cells was examined. ET-1 (10(-7) M) significantly increased
      intracellular free Ca2+ level ([Ca2+]i), 45Ca2+ uptake and catecholamine
      secretion in the cells. 2. ET-1 stimulated the efflux of 45Ca2+ from the cells
      preloaded with 45Ca2+ in a concentration-dependent manner (10(-9)-10(-7) M). This
      stimulatory effect was inhibited by ET(B) receptor antagonist BQ788, but not by
      ET(A) receptor antagonist BQ123. Selective ET(B) receptor agonists Suc-[Glu9,
      Ala11.5]-ET-1 and sarafotoxin S6c (SRTX) also stimulated 45Ca2+ efflux from the
      cells. 3. ET-1, Suc-[Glu9 Ala11.15]-ET-1 and SRTX increased the level of cyclic
      GMP in the adrenal chromaffin cells. ET-1 induced an increase in the nitric oxide
      (NO) level in the cells. The stimulatory effects by which ET- increases NO level
      and 45Ca2+ efflux were inhibited by NG-monomethyl-L-arginine acetate (L-NMMA), a
      competitive inhibitor of NO synthase. 4. The 45Ca2+ efflux stimulated by ET-1 was
      inhibited by deprivation of extracellular Na+, but not by deprivation of Ca2+. 5.
      These results suggest that ET-1 stimulates an extracellular Na+-dependent Ca2+
      efflux through the activation of NO synthase in cultured bovine adrenal
      chromaffin cells.

PMID- 9776345
TI  - Effects of mitogen-activated protein kinase kinase inhibitor PD 098059 on antigen
      challenge of guinea-pig airways in vitro.
AB  - 1. It has been shown that activation of protein tyrosine kinases is the earliest
      detectable signalling response to FcepsilonRI cross-linking on mast cell.
      Following tyrosine kinase activation, a family of mitogen-activated protein
      kinases (MAPKs) was found to be activated as well. The present study examined the
      role of MAPK signalling cascade in in vitro model of allergic asthma using a
      specific MAPK kinase inhibitor PD 098059. 2. Guinea-pigs were passively
      sensitized with IgG antibody raised against ovalbumin (OA). Effects of PD 098059
      on OA-induced anaphylactic contraction of isolated bronchi and release of
      histamine and peptidoleukotrienes from chopped lung preparations were studied. 3.
      PD 098059 (10-50 microM) produced only minor reduction of maximal OA-induced
      bronchial contraction. In contrast, the rate of relaxation of OA-induced
      bronchial contraction was markedly faster in the presence of PD 098059 than the
      vehicle control in a concentration-dependent manner. 4. These observations
      corroborate well with the inability of PD 098059 (5-50 microM) to substantially
      block the OA-induced release of histamine and with marked inhibition of OA
      induced release of peptidoleukotrienes from lung fragments in the presence of PD
      098059. Exogenous arachidonic acid-induced release of peptidoleukotrienes from
      lung fragments was not blocked by PD 098059. 5. In immunoblotting study, we found
      that p42MAPK was constitutively expressed in guinea-pig bronchi. However,
      treatment with OA, histamine or LTD4 did not cause activation of p42MAPK. These
      findings together with the lack of inhibitory effects of PD 098059 on bronchial
      contraction induced by histamine or LTD4 suggest that histamine- and LTD4-induced
      bronchial contractions are not mediated by p42MAPK activation. 6. Taken together,
      our findings show that inhibition of MAPK signalling cascade by PD 098059
      significantly reduced the OA-triggered release of peptidoleukotrienes leading to
      rapid relaxation of anaphylactic bronchial contraction. On the other hand,
      p42MAPK did not play a role in histamine- or LTD4-induced bronchial smooth muscle
      contraction suggesting that PD 098059 exerts its inhibitory effects on OA-induced
      bronchial contraction primarily through inhibition of peptidoleukotrienes release
      from mast cells.

PMID- 9776346
TI  - 5-hydroxytryptamine receptors mediating vasoconstriction and vasodilation in
      perinatal and adult rabbit small pulmonary arteries.
AB  - 1. Vasoconstrictor responses to 5-HT, 5-carboxamidotryptamine (5-CT, 5-HT1
      receptor agonist), alpha-methyl-5-HT (5-HT2 receptor agonist) and sumatriptan (5
      HT1D/1B receptor agonist) were studied in fetal, 0-24 h, 4 day, 7 day and adult
      rabbit pulmonary resistance arteries (PRAs), alone and in the presence of the NO
      synthase inhibitor Nomega-nitro-L-arginine methylester (L-NAME). The effect of
      the selective 5-HT receptor antagonists ketanserin (5-HT2A receptor) and GR55562
      (5-HT1B/1D receptor) on vasoconstrictor responses to 5-HT were studied in the
      presence of L-NAME. Vasodilator responses to 5-CT were also studied in pre
      contracted PRAs. 3. 5-HT and alpha-methyl-5-HT were equipotent in causing
      contraction in the PRAs at each age (e.g. pEC50s for 5-HT and alpha-methyl-5-HT
      were 6.74+/-0.13 and 6.63+/-0.22 respectively in adult vessels). In the perinatal
      PRAs, sumatriptan and 5-CT produced negligible contractions, but in adult PRAs, 5
      CT and sumatriptan were potent agonists with pEC50s of 6.05+/-0.3 and 5.70+/-0.20
      respectively. 4. L-NAME markedly increased the maximum response to 5-HT in the 0
      24 h, 4 day and 7 day vessels and increased 5-HT potency in the 4-, 7-day-old and
      adult rabbit vessels. 5. In perinatal vessels, responses to 5-HT, with L-NAME
      present, were antagonized by ketanserin (30 nM and 0.1 microM) but not GR55562 (1
      microM). A small ketanserin-resistant, GR55562-sensitive component was observed
      at 0-24 h. In adult vessels, both ketanserin and GR55562 inhibited 5-HT-induced
      responses. 7. Vasodilator responses to 5-CT were observed in pre-contracted PRAs
      from 4- and 7-day-old rabbits but not in the fetus, 0-24 h old or adult rabbit
      vessels. At 4 days the vasodilator response was inhibited both by L-NAME and
      GR55562. At 7 days the response was only partly blocked by L-NAME and resistant
      to GR55562. The L-NAME resistant component was antagonized by the 5-HT7 receptor
      antagonist spiperone (1 microM). 8. The results suggest that 5-HT2A-receptors
      mediate vasoconstriction in perinatal vessels whilst the 5-HT1D or 5-HT1B
      receptor contributes in adult rabbit vessels. The 5-HT1D or 5-HT1B receptor
      mediates NO-dependent vasodilation in vessels from rabbits at 4 days of age
      whilst 5-HT7 receptors mediate NO-independent vasodilation by 7 days.

PMID- 9776348
TI  - Peripheral and/or central effects of racemic-, S(+)- and R(-)-flurbiprofen on
      inflammatory nociceptive processes: a c-Fos protein study in the rat spinal cord.
AB  - 1. We have evaluated the effects of intravenous or intraplantar racemic-, S(+)-
      and R(-)-flurbiprofen on both the carrageenan-evoked peripheral oedema and spinal
      c-Fos immunoreactivity, an indirect index of neurons involved in spinal
      nociceptive processes. 2. Three hours after intraplantar injection of carrageenan
      (6 mg in 150 microl of saline) in awake rats, a peripheral oedema and numerous c
      Fos protein-like immunoreactive (c-Fos-LI) neurons in L4 L5 segments were
      observed. c-Fos-LI neurons were essentially located in the superficial (I-II) and
      deep (V-VI) laminae of the dorsal horn. 3. Intravenous racemic-flurbiprofen (0.3,
      3 and 9 mg kg(-1)) dose-relatedly reduced the carrageenan-evoked oedema and
      spinal c-Fos expression (r=0.64, r=0.88 and r=0.84 for paw diameter, ankle
      diameter and number of c-Fos-LI neurons; P<0.05. P<0.001 and P<0.001
      respectively). 4. Similar effects to those of intravenous racemic-flurbiprofen
      were obtained with intravenous S(+)-flurbiprofen (0.3, 3 and 9 mg kg(-1)) which
      dose-relatedly reduced the number of c-Fos-LI neurons (r=0.69, P<0.01) and
      diameters of paw and ankle (r=0.56 and r=0.52 respectively, P<0.05 for both). 5.
      For the dose of 0.3 mg kg(-1) i.v., R(-)-flurbiprofen did not modify the number
      of c-Fos-LI neurons and produced a weak reduction of oedema at only the ankle
      level (23+/-12% reduction, P<0.05). However, a ten times higher dose of R(-)
      flurbiprofen (3 mg kg(-1) i.v.) was necessary to obtain effects comparable to
      those of S(+)- or racemic-flurbiprofen (0.3 mg kg(-1) i.v.). 6. Intraplantar
      racemic-flurbiprofen (1, 10 and 30 microg) dose-relatedly reduced the carrageenan
      enhanced ankle diameter (r=0.81, P<0.001) and the number of c-Fos-LI neurons in
      L4-L5 segments (r=0.83, P<0.001). with a 60+/-3% reduction of the number of c-Fos
      LI neurons (P<0.001), and 30+/-3 and 67+/-7% reduction of paw and ankle diameter
      respectively (P<0.001 for both) for the dose of 30 microg. 7. For intraplantar
      S(+)-flurbiprofen (1, 10 and 30 microg) the dose-related effects (r=0.77, r=0.60
      and r=0.59 for c-Fos-LI neurons, paw and ankle diameters respectively, P<0.001,
      P<0.01 and P<0.01) were similar to those of racemic-flurbiprofen. In contrast,
      intraplantar R(-)-flurbiprofen (1, 10 and 30 microg) did not have detectable
      effects on all studied parameters. 8. The present study provides clear evidence
      for potent anti-inflammatory and antinociceptive effects of both intravenous or
      intraplantar racemic- and S(+)-flurbiprofen. These results further demonstrate
      marked anti-inflammatory and antinociceptive effects of intravenous, but not
      intraplantar, R(-)-flurbiprofen. These results suggest that the main site of
      action of racemic- and S(+ )-flurbiprofen is in the periphery and indicate that
      the site of action of R(-)-flurbiprofen is mainly of central origin.

PMID- 9776347
TI  - Augmented myocardial ischaemia by nicotine--mechanisms and their possible
      significance.
AB  - 1. To study the effect of nicotine on the severity of experimental myocardial
      ischaemia, Langendorff hearts of rabbits (n=7-12 per group) were subjected to 2 h
      of low-flow ischaemia followed by 1 h of reperfusion. 2. Infusion of nicotine
      (100 ng ml(-1)) caused only minor changes in non-ischaemic conditions but a
      significant (P<0.05) increase in end-diastolic pressure (LVEDP), loss of creatine
      kinase (CK) and troponin (TnT) as well as increase in noradrenaline (NA) overflow
      in reperfused ischaemic hearts. 3. RT PCR was done on total RNA for mRNA
      expression of the constitutive (COX-1) and inducible cyclooxygenase (COX-2).
      There was no COX-2 in non-ischaemic hearts but a significant expression in
      ischaemia (n=5) which was further increased by nicotine. These data were
      confirmed at the protein level by Western blotting and additionally shown that
      COX-1 remained unchanged. 4. There was a marked increase in prostacyclin (PGI2)
      and a 2 fold increase in NA overflow which were both stimulated by nicotine. 5.
      The aggravating effects of nicotine on myocardial ischaemia (CK release) as well
      as the expression of COX-2 mRNA were prevented by pretreatment with the beta
      blocker pindolol (1 microM). 6. The data demonstrate marked deleterious actions
      of nicotine in reperfused ischaemic hearts. These actions are probably related to
      the increase in catecholamine overflow, are beta-receptor-mediated and involve
      enhanced gene expression of COX-2.

PMID- 9776349
TI  - Influence of aminoguanidine on parameters of liver injury and regeneration
      induced in rats by a necrogenic dose of thioacetamide.
AB  - 1. When aminoguanidine, a nucleophilic hydrazine compound, was administered to
      rats (50 mg kg(-1) body wt) 30 min before a necrogenic dose of thioacetamide (500
      mg kg(-1) body wt), significant changes related to liver injury and
      hepatocellular regeneration were observed. 2. The extent of necrosis was
      noticeably less pronounced, as detected by the peak of serum aspartate
      aminotransferase activity. Depletion of hepatic glutathione (GSH) and the
      increase in malondialdehyde concentration as markers of oxidative stress,
      produced by thioacetamide metabolism, were significantly diminished. However, the
      activity of microsomal FAD monooxygenase, the system responsible for
      thioacetamide oxidation, did not show significant alterations. Antioxidant enzyme
      systems involved in the glutathione redox cycle, such as glutathione reductase
      and glutathione peroxidase activities, slightly decreased following
      aminoguanidine pretreatment. 3. Primary cultures of peritoneal macrophages from
      control rats, when incubated in the presence of serum collected following
      thioacetamide intoxication, showed a significant decrease in nitric oxide (NO)
      release at 24 h, that was more pronounced in the group pretreated with
      aminoguanidine. However, the sharp and progressive increase in macrophage NO
      release, when incubated in the presence of serum obtained at 48, 72 and 96 h,
      were increased by aminoguanidine-pretreatment. 4. The cell population involved in
      DNA synthesis sharply increased in both groups at 48 h of intoxication, although
      the values at 0, 24, 72 and 96 h were markedly higher in the group pre-treated
      with aminoguanidine. Polyploidy at 72 and 96 h of intoxication was delayed by the
      effect of aminoguanidine and a progressive increase in the hypodiploid hepatocyte
      population, which reached 16% of the total at 96 h, was observed. 5. These
      results indicate that a single dose of aminoguanidine before thioacetamide
      administration, markedly diminished the severity of the liver injury by
      decreasing oxidative stress and lipoperoxidation, but hepatocellular regeneration
      was apparently unaffected probably due to an enhanced mitogenic activity.

PMID- 9776350
TI  - Human vascular to cardiac tissue selectivity of L- and T-type calcium channel
      antagonists.
AB  - 1. Voltage-operated calcium channel (VOCC) antagonists are effective
      antihypertensive and antianginal agents but they also depress myocardial
      contractility. 2. We compared four L-type calcium channel antagonists,
      felodipine, nifedipine, amlodipine and verapamil and a relatively T-type
      selective calcium channel antagonist, mibefradil, on human and rat isolated
      tissue assays to determine their functional vascular to cardiac tissue
      selectivity (V/C) ratio. 3. The V/C ratio was calculated as the ratio of the IC50
      value of the antagonist that reduced (by 50%) submaximally contracted (K+ 62 mM)
      human small arteries from the aortic vasa vasorum (vascular, V) mounted in a
      myograph and the IC50 value of the antagonist that reduced (-)-isoprenaline (6
      nM) submaximally stimulated human right atrial trabeculae muscle (cardiac, C)
      mounted in organ chambers. 4. The average pIC50 values (-log IC50 M) for the
      human vascular preparations were felodipine 8.30, nifedipine 7.78, amlodipine
      6.64, verapamil 6.26 and mibefradil 6.22. The average pIC50 values for the
      cardiac muscle were felodipine 7.21, nifedipine 6.95, verapamil 6.91, amlodipine
      5.94, and mibefradil 4.61. 5. The V/C ratio calculated as antilog [pIC50V-pIC50C]
      is thus mibefradil 41, felodipine 12, nifedipine 7, amlodipine 5 and verapamil
      0.2. 6. In rat small mesenteric arteries the pIC50 values for the five drugs were
      similar to the values for human vasa vasorum arteries contracted by K+ 62 mM.
      However for methoxamine (10 microM) contraction in the rat arteries the pIC50
      values were lower for felodipine 7.24 and nifedipine 6.23, but similar for
      verapamil 6.13, amlodipine 6.28 and mibefradil 5.91. 7. In conclusion. in the
      human tissue assays, the putative T-channel antagonist mibefradil shows the
      highest vascular to cardiac selectivity ratio; some 3 fold higher than the
      dihydropyridine, felodipine, and some 200 fold more vascular selective than the
      phenylalkylamine, verapamil. This favourable vascular to cardiac selectivity for
      mibefradil, from a new chemical class of VOCC antagonist, may be explained by its
      putative T-channel selectivity.

PMID- 9776351
TI  - Differential effect of propofol on sympathetic neurotransmission in isolated
      human omental arteries and veins.
AB  - 1. The present study was undertaken to elucidate the effect of propofol on
      sympathetic neurotransmission in isolated human omental vessels. 2. Segments of
      both arteries and veins were exposed to 0, 10(-7), 10(-6), 10(-5) or 10(-4)M
      propofol, and studied in vitro to determine effects on: (i) isometric tension
      after electrical field stimulation (EFS) or after exogenous administration of
      noradrenaline (NA); (ii) EFS-stimulated release of [3H]-NA from vessel segments
      preincubated with [3H]-NA; (iii) uptake of [3H]-NA. 3. Propofol at 10(-6) M
      enhanced EFS-induced contraction in artery segments, 10(-7) and 10(-5) M had no
      effect, and 10(-4) M propofol depressed EFS-induced contraction in both artery
      and vein segments. 4. Propofol did not affect the response to exogenous NA in
      artery and vein segments. 5. EFS-stimulated release of [3H]-NA was depressed by
      10(-5) and 10(-4) M propofol in artery segments, and by 10(-4) M in vein
      segments. 6. Uptake of [3H]-NA was depressed by 10(-6)-10(-4) M propofol in
      artery but not in vein segments. 7. The results suggest that sympathetic
      neurotransmission is enhanced at clinical concentrations (10(-6) M) of propofol
      in human omental arteries, but not veins. This may be due to an increased
      availability of NA in the neuromuscular junction resulting from a reduced
      presynaptic reuptake. Propofol at probably supraclinical concentrations (10(-5)
      10(-4) M) impairs the sympathetic neurotransmission in both human omental
      arteries and veins, probably due to an inhibitory effect on the NA release from
      the sympathetic nerves.

PMID- 9776352
TI  - Rilmenidine reveals differences in the pharmacological characteristics of
      prejunctional alpha2-adrenoceptors in the guinea-pig, rat and pig.
AB  - 1. The alpha2A and alpha2D-adrenoceptor subtypes are thought to be species
      homologs most easily differentiated on the basis of the potency of antagonists.
      In the present study we have compared the effect of rilmenidine with two other
      selective alpha2-adrenoceptor agonists, UK-14304 (5-bromo-6- [2-imidazolin-2
      ylamino]-quinoxaline) and clonidine, against electrically-evoked contractions in
      five isolated preparations from the rat, guinea-pig and pig, and, where possible,
      determined the receptor subtype involved. 2. UK-14034, clonidine and rilmenidine
      produced concentration-dependent inhibition of the electrically-evoked
      contractions of the rat isolated vas deferens and tail artery and the guinea-pig
      ileum. These inhibitory effects were reversed by the selective alpha2
      adrenoceptor antagonist, RX-811058 (1 microM), except in the rat tail artery
      preparations where the remaining neurogenic response was inhibited; evidence for
      the involvement of 'innervated' alpha2-adrenoceptors. Both clonidine and UK-14304
      produced concentration-dependent inhibition of responses in the porcine isolated
      tail artery and urinary bladder but clonidine was markedly less efficacious in
      these preparations. In contrast, rilmenidine failed to inhibit the neurogenic
      contractions in either preparation. 3. Although rilmenidine failed to elicit a
      detectable response in either the porcine isolated tail artery or urinary
      bladder, it (10 microM and 30 microM, respectively) competitively antagonised the
      inhibitory effects of UK-14304 with an estimated dissociation constant of (pK(B))
      5.82 and 5.93, respectively. 4. Prazosin (1 microM) failed to alter the effect of
      UK-14304 against neurogenic contractions in the porcine isolated urinary bladder,
      while rauwolscine (pK(B) 8.87) was 10 fold more potent than phentolamine (pK(B)
      7.56). On the other hand, phentolamine (pK(B) 8.42) was only marginally more
      potent than rauwolscine (pK 8.05) against clonidine-induced inhibition of
      electrically-evoked contractions of the guinea-pig isolated ileum. This
      pharmacological evidence with antagonists supports the presence of alpha2D
      adrenoceptors in the rat and guinea-pig and the alpha2A-adrenoceptors in the pig.
      5. We have demonstrated that rilmenidine, unlike clonidine and UK-14304, is
      devoid of any agonist activity at prejunctional alpha2A-adrenoceptors in the pig,
      but is an efficacious agonist at alpha2D-adrenoceptors in the rat and guinea-pig.

PMID- 9776353
TI  - Effect of chronic hypoxia on adrenoceptor responses of ovine foetal umbilical
      vessels.
AB  - 1. The effects of chronic hypoxia on alpha1-adrenoceptor-mediated contractions
      were investigated in foetal umbilical vessels obtained from near-term
      (approximately 140 day gestation) pregnant sheep maintained near sea level ( 300
      m) and at high altitude (3820 m) from 30 day gestation. 2. Chronic hypoxia
      significantly decreased contractile sensitivity of the umbilical vein to
      noradrenaline (pD2: 6.22+/-0.19 vs 5.67+/-0.09) and reduced the maximum response
      by 43%. Noradrenaline-induced contraction of the umbilical artery was abolished.
      In contrast, contractions to KCI were not affected by chronic hypoxia. 3. In
      umbilical vein, the apparent dissociation constant (KA) of noradrenaline to
      alpha1-adrenoceptors was increased from 0.54+/-0.06 microM in control animals to
      1.35+/-0.14 microM in chronically hypoxic animals. In accordance, radioligand
      binding of agonist showed high and low affinity binding sites for noradrenaline
      in both normoxic and chronically hypoxic tissues. Addition of GTPgammaS (100
      microM) abolished apparent high affinity binding sites. Whereas proportional
      binding sites were not changed by chronic hypoxia, the apparent high affinity of
      noradrenaline was significantly decreased (pKi: 7.80+/-0.17 vs 7.20+/-0.16). 4.
      Chronic hypoxia significantly decreased alpha1-adrenoceptor density (fmol mg
      protein(-1)) in umbilical vein (24.6+/-3.2 vs 12.3+/-3.1) and the artery (7.1+/
      0.4 vs 3.1+/-0.9) with no change in [3H]-prazosin binding affinity. There was a
      linear correlation of the maximum contractions to noradrenaline and alpha1
      adrenoceptor density. 5. We conclude that chronically hypoxic-induced depression
      in contractions of ovine foetal umbilical vessels to noradrenaline is mediated
      predominantly by decreases in alpha1-adrenoceptor density and the agonist binding
      affinity.

PMID- 9776354
TI  - Kinin B2 receptor-mediated contraction of tail arteries from normal or
      streptozotocin-induced diabetic rats.
AB  - 1. The vasoactive effects of bradykinin (BK) are mediated by different subtypes
      of kinin receptors, of which the expression varies among different tissues. In
      rat tail artery tissues, BK elicited a concentration-dependent vasoconstriction
      (EC50, 25.9+/-2.4nM; Emax, 0.39+/-0.01 g; n=16). This effect of BK was
      endothelium independent and indomethacin insensitive. The BK-induced contraction
      of tail artery tissues, however, depended on both membrane potential-sensitive
      extracellular Ca2+ entry and thapsigargin-sensitive intracellular Ca2+ release.
      2. Kinin B1 receptor antagonist or agonist did not affect the basal tension or
      the BK-induced contraction of tail artery tissues in the absence or presence of
      endothelium (P>0.05). In contrast, the BK-induced vasoconstriction was inhibited
      by kinin B2 receptor antagonists. Pretreatment of vascular tissues with Hoe 140
      (1 nM) significantly changed EC50 of the BK-induced vasoconstriction from 25.5+/
      7.4 nM to 82.6+/-16.8nM (n=8, P<0.01) and Emax from 0.43+/-0.03g to 0.16+/-0.01 g
      (n=8, P<0.01). 3. In the tail artery tissues from streptozotocin-induced diabetic
      rats, the BK-elicited vasoconstriction was significantly reduced (EC50, 67.8+/-11
      nM: Emax, 0.19+/-0.01 g) compared to their counterparts from normal rats. The
      decreased vasoconstrictive effects of BK on diabetic arteries were endothelium
      independent and indomethacin insensitive. 4. Our study demonstrated that the
      contraction of rat tail arteries induced by BK was mediated by B2 receptors
      located on vascular smooth muscles. The altered B2 receptor-mediated vascular
      activity may play an important role in the vascular complications of diabetes.

PMID- 9776355
TI  - Inhibition of chemotaxis in A7r5 rat smooth muscle cells by a novel panel of
      inhibitors.
AB  - 1. Arginine-specific ADP-ribosyltransferase (ART) activity has been implicated in
      white cell chemotaxis. In this study, we examined the capacity of a panel of
      structurally unrelated inhibitors and pseudosubstrates of ART to inhibit
      chemotaxis of A7r5 rat vascular smooth muscle cells in response to PDGF-BB. 2.
      The IC50 values for nicotinamide (12 mM) and novobiocin (165 microM) were similar
      to those observed for inhibition of chemotaxis by human polymorphonuclear
      neutrophil leucocytes (PMN), whereas vitamins K3 (IC50=22 microM) and K1 (IC50=95
      microM) were less potent than previously described in PMNs. The pseudo-substrates
      for the enzyme (DEA-BAG, agmatine and arginine-methylester) also inhibited A7r5
      chemotaxis, and in addition inhibited cell adhesion at similar concentrations.
      Vitamin K3 was unique among the inhibitors of ART, in that it also inhibited cell
      adhesion. 3. A rat ART1 transcript was amplified by rtPCR from rat skeletal
      muscle, and was noted to share 94% homology with the mouse ART1 cDNA sequence. No
      such transcript could be detected in A7r5 cells by Northern blot analysis or
      rtPCR. 4. Evidence for ART activity on the surface of A7r5 cells was investigated
      using 32P-NAD+ as substrate, and labelled membrane proteins were observed with
      MWt values of 116, 100, 90 and 70 kDa. Exposure of the labelled proteins to
      phosphodiesterase yielded 32P-AMP, and hydrolysis with NaOH yielded 32P-NAD+.
      These results indicated that the labelled proteins were adducts with NAD+, and
      not the products of ART activity. The absence of ART catalytic activity in A7r5
      cells was confirmed in protocols designed to show ADP-ribosylation of agmatine.
      5. We conclude that the chemotactic activity of A7r5 cells is independent of ART
      activity, and the mechanism whereby the novel panel of inhibitors reduced cell
      migration remains undefined.

PMID- 9776357
TI  - Involvement of barium-sensitive K+ channels in endothelium-dependent vasodilation
      produced by hypercapnia in rat mesenteric vascular beds.
AB  - 1. We examined the vasodilatory effect of hypercapnia in the rat isolated
      mesenteric vascular bed. The preparation was perfused constantly (5 ml min(-1)
      with oxygenated Krebs-Ringer solution, and the perfusion pressure was measured.
      In order to keep the extracellular pH (pHe) constant (around 7.35) against a
      change in CO2, adequate amounts of NaHCO3 were added to Krebs-Ringer solution. 2.
      In the endothelium intact preparations, an increase in CO2 from 2.5% to 10% in
      increments of 2.5% decreased the 10 microM phenylephrine (PE)-produced increase
      in the perfusion pressure in a concentration-dependent manner. Denudation of the
      endothelium by CHAPS (3-[(3-cholamidopropyl)-dimethylammonio]-1
      propanesulphonate) (5 mg l(-1), 90 s perfusion) abolished the vasodilatory effect
      of hypercapnia. 3. An increase in CO2 from 5% to 10% reduced the increases in the
      perfusion pressure produced by 10 microM PE and 400 nM U-46619 by 48% and 44%,
      respectively. NG-monomethyl-L-arginine (100 microM) and indomethacin (10 microM)
      did not affect the vasodilatory effect of hypercapnia, whereas the vasodilatory
      response of the preparation to hypercapnia disappeared when the preparation was
      contracted by 60 mM K+ instead of PE or U-46619. 4. The vasodilatory effect of
      hypercapnia observed in the PE- or U-46619-precontracted preparation was affected
      by neither tetraethylammonium (1 mM), apamin (500 microM), glibenclamide (10
      microM), nor 4-aminopyridine (1.5 mM). On the other hand, pretreatment with Ba2+
      at a concentration of 0.3 mM abolished the hypercapnia-produced vasodilation. 5.
      An increase in the concentration of K+ in Krebs-Ringer solution from 4.5 mM to
      12.5 mM in increments of 2 mM reduced the PE-produced increase in the perfusion
      pressure in a concentration-dependent manner. Pretreatment of the preparations
      with not only Ba2+ (0.3 mM) but also CHAPS abolished the vasodilatory effect of
      K+. 6. The results suggest that an increase in CO2 produces vasodilation by an
      endothelium-dependent mechanism in the rat mesenteric vascular bed. The membrane
      hyperpolarization of the endothelial cell by an activation of the inward
      rectifier K+ channel seems to be the mechanism underlying the hypercapnia
      produced vasodilation. Neither nitric oxide nor prostaglandins are involved in
      this response.

PMID- 9776356
TI  - Assessment of the effect of malaria infection on hepatic clearance of
      dihydroartemisinin using rat liver perfusions and microsomes.
AB  - 1. The clearance of dihydroartemisinin (DHA) in control and malaria-infected (MI)
      rats was investigated using the isolated perfused rat liver (IPRL) model and
      hepatic microsomal studies. 2. In the recirculating IPRL, clearance of DHA was
      reduced from a mean (s.d.) of 8.2+/-1.8 ml min(-1) in controls (n=8) to 6.0+/-1.0
      ml min(-1) in MI (n=8; P<0.01). Clearance in control livers was similar to the
      perfusion flow rate, suggesting a high hepatic extraction ratio for DHA. 3.
      Single-pass IPRL studies in controls (n=8) showed that DHA bioavailability at
      1.3, 8 and 38 microm was 0.026+/-0.020, 0.043+/-0.025 and 0.14+/-0.06,
      respectively (P<0.001 for 8 microM vs 38 microM). In MI livers (n=5), DHA
      bioavailability at 8 and 38 microM was 0.18+/-0.07 and 0.40+/-0.08, respectively
      (P=0.002). Bioavailability was higher in the MI group than in controls (P=0.01 at
      8 microM and P<0.001 at 38 microM). DHA-glucuronide was the sole biliary
      metabolite. 4. Hepatic microsomal studies of DHA-glucuronide formation showed a
      significantly lower Vmax but no significant change in Km, in MI compared to
      control livers (n=6). Intrinsic metabolic clearance (Vmax/Km) was higher in
      control than in MI livers (5.2+/-1.3 and 2.5+/-1.4 microl min(-1) mg(-1),
      respectively; P=0.006). 5. These studies demonstrate that DHA has a high,
      concentration-dependent hepatic extraction ratio that is reduced by 20-30% in the
      P. berghei rodent malaria model. The impaired hepatic clearance of DHA in MI is
      attributable to a reduction in intrinsic metabolic clearance.

PMID- 9776358
TI  - Attenuation of tolerance to opioid-induced antinociception and protection against
      morphine-induced decrease of neurofilament proteins by idazoxan and other I2
      imidazoline ligands.
AB  - 1. Agmatine, the proposed endogenous ligand for imidazoline receptors, has been
      shown to attenuate tolerance to morphine-induced antinociception (Kolesnikov el
      al., 1996). The main aim of this study was to assess if idazoxan, an alpha2
      adrenoceptor antagonist that also interacts with imidazoline receptors, could
      also modulate opioid tolerance in rats and to establish which type of imidazoline
      receptors (or other receptors) are involved. 2. Antinociceptive responses to
      opioid drugs were determined by the tail-flick test. The acute administration of
      morphine (10 mg kg(-1), i.p., 30 min) or pentazocine (10 mg kg(-1), i.p., 30 min)
      resulted in marked increases in tail-flick latencies (TFLs). As expected, the
      initial antinociceptive response to the opiates was lost after chronic (13 days)
      treatment (tolerance). When idazoxan (10 mg kg(-1), i.p.) was given chronically
      30 min before the opiates it completely prevented morphine tolerance and markedly
      attenuated tolerance to pentazocine (TFLs increased by 71-143% at day 13).
      Idazoxan alone did not modify TFLs. 3. The concurrent chronic administration (10
      mg kg(-1), i.p., 13 days) of 2-BFI, LSL 60101, and LSL 61122 (valldemossine),
      selective and potent I2-imidazoline receptor ligands, and morphine (10 mg kg(-1),
      i.p.), also prevented or attenuated morphine tolerance (TFLs increased by 64 172%
      at day 13). This attenuation of morphine tolerance was still apparent six days
      after discontinuation of the chronic treatment with LSL 60101-morphine. The acute
      treatment with these drugs did not potentiate morphine-induced antinociception.
      These drugs alone did not modify TFLs. Together, these results indicated the
      specific involvement of I2-imidazoline receptors in the modulation of opioid
      tolerance. 4. The concurrent chronic (13 days) administration of RX821002 (10 mg
      kg(-1), i.p.) and RS-15385-197 (1 mg kg(-1), i.p.), selective alpha2-adrenoceptor
      antagonists, and morphine (10 mg kg(-1), i.p.), did not attenuate morphine
      tolerance. Similarly, the concurrent chronic treatment of moxonidine (1 mg kg(
      1), i.p.), a mixed I(1)-imidazoline receptor and alpha2-adrenoceptor agonist, and
      morphine (10 mg kg(-1), i.p.), did not alter the development of tolerance to the
      opiate. These results discounted the involvement of alpha2-adrenoceptors and I(1)
      imidazoline receptors in the modulatory effect of idazoxan on opioid tolerance.
      5. Idazoxan and other imidazol(ine) drugs fully inhibited [3H]-(+)-MK-801 binding
      to N-methyl-D-aspartate (NMDA) receptors in the rat cerebral cortex with low
      potencies (Ki: 37-190 microM). The potencies of the imidazolines idazoxan,
      RX821002 and moxonidine were similar, indicating a lack of relationship between
      potency on NMDA receptors and ability to attenuate opioid tolerance. These
      results suggested that modulation of opioid tolerance by idazoxan is not related
      to NMDA receptors blockade. 6. Chronic treatment (13 days) with morphine (10 mg
      kg(-1), i.p.) was associated with a marked decrease (49%) in immunolabelled
      neurofilament proteins (NF-L) in the frontal cortex of morphine-tolerant rats,
      suggesting the induction of neuronal damage. Chronic treatment (13 days) with
      idazoxan (10 mg kg(-1)) and LSL 60101 (10 mg kg(-1)) did not modify the levels of
      NF-L proteins in brain. Interestingly, the concurrent chronic treatment (13 days)
      of idazoxan or LSL 60101 and morphine, completely reversed the morphine-induced
      decrease in NF-L immunoreactivity, suggesting a neuroprotective role for these
      drugs. 7. Together, the results indicate that chronic treatment with I2
      imidazoline ligands attenuates the development of tolerance to opiate drugs and
      may induce neuroprotective effects on chronic opiate treatment. Moreover, these
      findings offer the I2-imidazoline ligands as promising therapeutic coadjuvants in
      the management of chronic pain with opiate drugs.

PMID- 9776359
TI  - Relaxant effects of L-citrulline in rabbit vascular smooth muscle.
AB  - 1. Vascular endothelium plays a pivotal role in the control of vascular tone
      through the release of vasoactive factors such as EDRF (NO). 2. The aim of this
      study was to investigate whether the addition of exogenous L-citrulline, the
      byproduct of the NO-synthesis, could relax vascular smooth muscle. 3. L
      citrulline relaxed both endothelium-denuded and endothelium-intact rabbit aortic
      rings precontracted with noradrenaline 10(-6) M (maximum relaxations induced by L
      citrulline 10(-8) M were 74.1+/-5.2% vs 51.3+/-2.8% in endothelium-denuded and
      endothelium-intact arteries, respectively). 4. This relaxant effect was enhanced
      by zaprinast (a phosphodiesterase type 5 inhibitor) and inhibited by HS-142-1 (a
      particulate guanylate cyclase inhibitor) and by apamin (a K(Ca)-channel blocker).
      5. L-citrulline (10(-13)-10(-8) M) increased cGMP levels in aortic rings (maximum
      value with L-citrulline 10(-8) M was 0.165+/-0.010 pmol cGMP mg(-1) of tissue vs
      0.038+/-0.009 pmol mg(-1) of tissue in basal). 6. L-citrulline as well as NO were
      released from endothelial cells in culture stimulated with ACh. The values were
      6.50+/-0.50 microM vs 2.30+/-0.20 microM (stimulated with ACh and basal
      respectively) for L-citrulline and 4.22+/-0.10 microM vs 0.87+/-0.26 microM
      (stimulated with ACh and basal respectively) for NO. 7. These results suggest
      that L-citrulline could be released together with NO from endothelium and may
      have actions complementary to those of NO in the control of vascular smooth
      muscle relaxation.

PMID- 9776360
TI  - Cytokine induction of NO synthase II in human DLD-1 cells: roles of the JAK-STAT,
      AP-1 and NF-kappaB-signaling pathways.
AB  - 1. In human epithelial-like DLD-I cells, nitric oxide synthase (NOS) II
      expression was induced by interferon-gamma (100 u ml(-1)) alone and, to a larger
      extent, by a cytokine mixture (CM) consisting of interferon-gamma, interleukin
      1beta (50 u ml(-1)) and tumor necrosis factor-alpha (10 ng ml(-1)). 2. CM-induced
      NOS II expression was inhibited by tyrphostin B42 (mRNA down to 1%; nitrite
      production down to 0.5% at 300 microM) and tyrphostin A25 (mRNA down to 24%,
      nitrite production down to 1% at 200 microM), suggesting the involvement of janus
      kinase 2 (JAK-2). Tyrphostin B42 also blocked the CM-induced JAK-2
      phosphorylation (kinase assay) and reduced the CM-stimulated STAT1alpha binding
      activity (gel shift analysis). 3. CM reduced the nuclear binding activity of
      transcription factor AP-1. A heterogenous group of compounds, that stimulated the
      expression of c-fos/c-jun, enhanced the nuclear binding activity of AP-1. This
      group includes the protein phosphatase inhibitors calyculin A, okadaic acid, and
      phenylarsine oxide, as well as the inhibitor of translation anisomycin. All of
      these compounds reduced CM-induced NOS II mRNA expression (to 9% at 50 nM
      calyculin A; to 28% at 500 nM okadaic acid; to 18% at 10 microM phenylarsine
      oxide; and to 19% at 100 ng ml(-1) anisomycin) without changing NOS II mRNA
      stability. In cotransfection experiments, overexpression of c-Jun and c-Fos
      reduced promoter activity of a 7 kb DNA fragment of the 5'-flanking sequence of
      the human NOS II gene to 63%. 4. Nuclear extracts from resting DLD-1 cells showed
      significant binding activity for transcription factor NF-kappaB, which was only
      slightly enhanced by CM. The NF-kappaB inhibitors dexamethasone (1 microM), 3,4
      dichloroisocoumarin (50 microM), panepoxydone (5 microg ml(-1)) and pyrrolidine
      dithiocarbamate (100 microM) produced no inhibition of CM-induced NOS II
      induction. 5. We conclude that in human DLD-1 cells, the interferon-gamma-JAK-2
      STAT1alpha pathway is important for NOS II induction. AP-1 (that is downregulated
      by CM) seems to be a negative regulator of NOS II expression. NF-kappaB, which is
      probably important for basal activity of the human NOS II promoter, is unlikely
      to function as a major effector of CM in DLD-1 cells.

PMID- 9776362
TI  - Molecular cloning and functional characterization of a rat somatostatin sst2(b)
      receptor splice variant.
AB  - 1. The mouse somatostatin (SRIF) sst2 receptor exists in two splice variants,
      sst2(a) and sst2(b), which differ in their intracellular carboxy-termini only.
      The murine sst2(b) receptor was reported to be less prone to agonist-induced
      desensitization as compared with the sst2(a) receptor. To determine whether a
      sst2(b) splice variant with similar functional characteristics exists in the rat,
      we have isolated a cDNA fragment from rat gastric mucosa encoding a sst2(b)
      receptor and expressed the full-length protein in CHO-K1 cells for functional
      characterization. 2. This study provides the first evidence for the occurrence in
      the rat of the sst2(b) receptor, which has a 15 amino acid carboxy-terminus
      differing in composition to the 38 amino acid C-terminus of the rat sst2(a)
      receptor. 3. In CHO-K1 cells expressing rat recombinant sst2(a) or sst2(b)
      receptors, SRIF caused concentration-dependent increases in extracellular
      acidification rates (EAR) with pEC50 values of 9.0 and 9.9, respectively. Pre
      treatment with pertussis toxin (Ptx) caused a rightward displacement of the SRIF
      concentration-effect curves with pEC50 values of 8.3 (sst2(a) and 8.4 (sst2(b)).
      4. SRIF (3 pM-3 nM) also caused concentration-dependent inhibition of forskolin
      stimulated cyclic AMP formation in CHO-sst2(a) cells (pIC50 10.5) and CHO-sst2(b)
      cells (pIC50 10.4). The degree of inhibition was less with higher concentrations
      of SRIF resulting in bell-shaped concentration-effect curves. Following pre
      treatment with Ptx, the inhibitory effect of SRIF was abolished and SRIF caused
      only increases in cyclic AMP formation. 5. Both the SRIF-induced increases in EAR
      and inhibition of cyclic AMP formation were susceptible to agonist-induced
      desensitization, but this was less apparent following pre-treatment with Ptx. 6.
      This demonstrates that the operational characteristics of the recombinant rat
      sst2(a) and sst2(b) receptors are broadly similar. Both isoforms couple to Ptx
      sensitive as well as -insensitive G proteins and are equally prone to agonist
      induced desensitization.

PMID- 9776361
TI  - SB-224289--a novel selective (human) 5-HT1B receptor antagonist with negative
      intrinsic activity.
AB  - 1. Human 5-HT1B (h5-HT1B) and human 5-HT1D (h5-HT1D) receptors show remarkably
      similar pharmacology with few compounds discriminating the receptors. We report
      here on a novel compound, SB-224289 (1'-Methyl-5-[[2'-methyl-4'-(5-methyl- 1,2,4
      oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6,7-tetrahydro spiro [furo [2,3
      f]indole-3,4'-piperidine] oxalate), which has high affinity for h5-HT1B receptors
      (pK1=8.16+/-0.06) and displays over 75 fold selectivity for the h5-HT1B receptor
      over all other 5-HT receptors including the h5-HT1D receptor and all other
      receptors tested thus far. 2. Functional activity of SB-224289 was measured in a
      [15S]GTPgammaS binding assay on recombinant h5-HT1B and h5-HT1D receptors
      expressed in Chinese Hamster Ovary (CHO) cells. SB-224289 displayed negative
      intrinsic activity at both receptors with higher potency at h5-HT1B receptors. SB
      224289 caused a rightward shift of agonist concentration response curves
      consistent with competitive antagonism and generated affinities comparable with
      those obtained from competition radioligand receptor binding studies. 3. SB
      224289 potentiated [3H]5-HT release from electrically stimulated guinea-pig
      cerebral cortical slices to the same extent as as the non-selective 5-HT1
      antagonist methiothepin. SB-224289 also fully reversed the inhibitory effect of
      exogenously superfused 5-HT on electrically stimulated release. 4. Using SB
      224289 as a tool compound, we confirm that in guinea-pig cerebral cortex the
      terminal 5-HT autoreceptor is of the 5-HT1B subtype.

PMID- 9776363
TI  - Catecholamine transport by the organic cation transporter type 1 (OCT1).
AB  - 1. Liver and kidney extract adrenaline and noradrenaline from the circulation by
      a mechanism which does not seem to be one of the classical catecholamine
      transporters. The hypothesis that OCT1 is involved the organic cation transporter
      type 1 which exists in rat kidney and liver-was tested. 2. Based on human
      embryonic kidney cells (293), we constructed a cell line which stably expresses
      OCT1r (293OCT1r cells). Transfection with OCT1 resulted in a transport activity
      not only for prototypical known substrates of OCT1 such as 3H-1-methyl-4
      phenylpyridinium and 14C-tetraethylammonium but also for the catecholamines 3H
      adrenaline, 3H-noradrenaline (3H-NA) and 3H-dopamine (3H-DA), the indoleamine 3H
      5-hydroxytryptamine (3H-5HT) as well as the indirect sympathomimetic 14C
      tyramine. 3. For 3H-DA, 3H-5HT and 3H-NA, at non-saturating concentrations, the
      rate constants for inwardly directed substrate flux (kin) were 6.9+/-0.8, 3.1+/
      0.2, and 1.2+/-0.1 microl min(-1) mg protein(-1). In wild type cells (293WT) the
      corresponding kin's were considerably lower, being 0.94+/-0.40, 0.47+/-0.08 and
      0.23+/-0.05 microl min(-1) mg protein ' (n=12). The indirectly determined half
      saturating concentrations of DA, 5HT, and NA were 1.1 (95% c.i.: 0.8, 1.4), 0.65
      (0.49, 0.86), and 2.8 (2.1, 3.7) mmol l(-1) (n=3). 4. Specific 3H-DA uptake in
      293OCT1r cells was resistant to cocaine (1 micromoll(-1)), 3H-5HT uptake was
      resistant to citalopram (300 nmol l(-1)) and 3H-NA uptake was resistant to
      desipramine (100 nmoll(-1)), corticosterone (1 micromol l(-1)), and reserpine (10
      nmoll(-1)) which rules out the involvement of classical transporters for biogenic
      amines. 5. The findings demonstrate that OCTI efficiently transports
      catecholamines and other biogenic amines and support the hypothesis that OCT1 is
      responsible for hepatic and renal inactivation of circulating catecholamines.

PMID- 9776364
TI  - Evidence that S-adenosyl-L-methionine diastereoisomers may reduce ischaemia
      reperfusion injury by interacting with purinoceptors in isolated rat liver.
AB  - 1. Mechanisms underlying the haemodynamic activity of diastereoisomers of S
      adenosyl-L-methionine (SAM) were investigated using inhibitors of purinoceptors
      and nitric oxide (NO) synthase in perfused rat livers damaged by sequential 24 h
      cold and 20 min rewarming ischaemia + reperfusion. 2. Stored livers were flushed
      with 10 ml saline alone (control) or with added (R,S) or (S,S) SAM (100 microM)
      and reperfused in the absence (control) or presence of 10 microM 8
      phenyltheophylline (8-PT) or 100 microM L-N-monomethylarginine (L-NMMA). 3. Both
      SAM diastereoisomers rapidly increased blood flow and bile production versus
      controls (P<0.001) but the (R,S) isomer induced greater increases in blood flow
      and the (S,S) isomer greater increases in bile production: 625 versus 596 versus
      518 ml blood flow and 100 versus 119 versus 56 mg bile production per g liver
      over 3 h in (R,S), (S,S) and control, respectively. 4. 8-PT prevented the
      enhancement of blood flow by (S,S) SAM (529 versus 596 ml g(-1) liver over 3 h
      for (S,S) SAM alone, P<0.001), but was without effect in control livers. 8-PT
      also reduced SAM-enhanced bile production: 51 versus 119 mg g(-1) liver over 3 h,
      P<0.001. L-NMMA reduced blood flow and bile production similarly in the absence
      or presence of (S,S) SAM. 5. Thus, SAM may improve liver perfusion after
      ischaemia-reperfusion injury via stimulation of P, (A2) purinoceptors at which
      SAM shows activity. The choleretic activity of (S,S) SAM is disproportionately
      greater than enhanced blood flow and may occur independently of a NO-dependent
      component of bile production.

PMID- 9776365
TI  - Psycho-oncology research: the road traveled, the road ahead.

PMID- 9776366
TI  - Group therapy in the cancer setting.

PMID- 9776367
TI  - The role of the clinical psychologist in gynecological cancer.
AB  - Gynecological cancers, which account for a substantial proportion of cancer cases
      in women, can precipitate a wide range of psychological difficulties including
      affective disturbances, sexual problems, certain somatic symptoms, and family
      issues. The clinical psychologist has a unique contribution to make in the
      assessment and treatment of the psychological needs of gynecological cancer
      patients, while also conducting research and providing training for health
      professionals regarding the psychological issues associated with gynecological
      cancer. Although the gynecological cancer setting affords the clinical
      psychologist multiple personal benefits, strategies must usually be implemented
      to minimize any negative impact arising from working in an area of considerable
      psychological stress.

PMID- 9776368
TI  - Assessment and treatment of depression in the cancer patient.
AB  - The prevalence, diagnosis, and treatment of depression in the cancer patient are
      reviewed. Although frequently encountered in the cancer patient population,
      depression often remains undiagnosed and untreated. This carries grave
      consequences in that depressed cancer patients experience a poorer quality of
      life, are less compliant with medical care, have longer hospital stays, and have
      higher mortality rates. Diagnostic assessment of depression in the cancer patient
      raises difficulties both upon phenomenological and etiological grounds. In
      particular, the presence of neurovegetative symptoms which may be secondary to
      either cancer or depression may cloud the diagnostic picture. Due to the serious
      consequences of unrecognized depression, a more sensitive inclusive approach to
      diagnosis is recommended in the clinical setting. Finally, the limited data
      regarding treatment of depression in patients with cancer is reviewed. This
      includes a discussion of both psychosocial and pharmacological interventions
      which are shown to alleviate depression, improve quality of life measures,
      improve immune function, and lengthen survival time.

PMID- 9776369
TI  - Cancer in married couples: higher or lower distress?
AB  - This study focuses on the question of what occurs when both spouses become
      seriously ill. Our hypothesis was that psychological distress in married couples
      involving two ill partners is far higher than when only one partner is ill. The
      study group comprised 20 married couples, in which both spouses were diagnosed
      with cancer. Two comparison groups were also studied: 20 married couples with the
      husband diagnosed with cancer, and 20 couples with the wife diagnosed with
      cancer. All patients in the three groups completed four self-report scales: the
      Brief Symptom Inventory (BSI); the Perceived Family Support (PFS); the Impact of
      Events Scale (IES); and the Mental Adjustment to Cancer (MAC). The healthy
      spouses completed only the first three scales. Our findings supported the null
      hypothesis--that is, that the psychological distress in married couples with both
      partners diagnosed with cancer was not significantly different than when only one
      partner had cancer. Our findings also showed that neither sociodemographic
      background, medical condition, nor family support affect patient distress. Gender
      differences were found with Intrusiveness contributing to the distress of male,
      but not female, patients. This study confirms and augments earlier work, and
      shows that partners of cancer patients report a high degree of distress, with
      this level of distress not being much different from that of the patients.

PMID- 9776370
TI  - Persistent somatization in cancer: a controlled follow-up study.
AB  - Nature and frequency of somatic complaints, severity of anxiety and depression,
      and nature of psychiatric symptoms and disorders were evaluated in 81 adequately
      treated cancer patients, disease-free or with residual disease, using a
      controlled, prospective follow-up design. Patients were included in the index
      group (n=60) if they had persistent somatic complaints or unexplained nature or
      severity of somatic complaints, or the control group (n=21), if they did not
      report somatic complaints. Instruments used for evaluation were the Scale for
      Assessment of Somatic Symptoms, Hospital Anxiety and Depression Scale,
      Psychiatric Assessment Schedule, and DSM-III-R. Common somatic complaints in the
      index group were pain (19%), fatigue (17%), sensory symptoms (30%), and mixed
      symptoms (27%). Subjects in the index group significantly (p<0.001) more often
      had depressive or anxiety disorder (19%) and atypical somatoform disorder (15%).
      Patients were treated appropriately with psychotropic medications and counseling.
      Follow-up at 4-6 months revealed a significant reduction in the number of somatic
      symptoms (p<0.001) and anxiety (p<0.001) and depression (p<0.05) scores. The
      observations confirm that somatic symptoms may persist in cancer patients, which
      are related to concomitant psychopathology, and require psychiatric intervention.

PMID- 9776371
TI  - Awareness of diagnosis and psychiatric morbidity among cancer patients--a study
      from South India.
AB  - Awareness regarding cancer diagnosis and its relationship to psychiatric
      morbidity was studied in 294 newly admitted cancer patients at an oncology center
      in South India. Fifty-four percent of patients were aware that they had cancer
      and were able to discuss their diagnosis; 46% of patients reported nonawareness
      of diagnosis. Discriminant function analysis revealed that oral cancers and
      relatives' awareness of the cancer was more prevalent in the group aware of
      diagnosis. More patients in the "unaware" group refused treatment for
      psychological distress. There was no difference between the two groups in
      patterns and prevalence of psychiatric morbidity. The study emphasizes the
      complexities in assessing awareness in cancer patients and a need to study its
      various components and relationship to psychological distress.

PMID- 9776372
TI  - Correlates of participation in a breast cancer support group.
AB  - We identified correlates of participation in a breast cancer support group.
      Thirty-eight breast cancer patients were classified as established members, new
      members, or nonmembers of breast cancer support groups and were administered a
      Background Data Sheet, Medical Questionnaire, and the Personality Assessment
      Inventory. Established members were most educated, had the most friends with
      cancer, perceived group as more supportive than new members, and identified
      coping skills and sense of community as the most helpful features of group; new
      members held longer meetings than established members, rated their relatives as
      least supportive, and cited medical information as the most beneficial feature of
      group. Established members manifested the least anxiety, depression, stress,
      nonsupport, and aggression. We integrate these findings with the literature on
      social support and cancer and offer suggestions for research and practice.

PMID- 9776373
TI  - Understanding the level of fatigue in cancer patients undergoing radiotherapy.
AB  - This study tests the hypothesis that a discrepancy between resources and demands
      explains most of the variance in fatigue in cancer patients undergoing
      radiotherapy. Patients (n=250) were interviewed at pretreatment, posttreatment,
      and at 9-month follow-up. Resources involved physical condition, neuroticism,
      optimism, social support, gender, age, and level of education. Demands entailed
      prognosis, radiotherapy dose, the effort associated with actual activity, and the
      patient's perception of overall burden. Regression analyses were performed, using
      interaction terms to operationalize the discrepancy between resources and
      demands. The hypothesis was not supported. At pretreatment, physical condition
      explained most of the fatigue, whereas, at posttreatment, both the patients'
      physical condition and perception of burden contributed to fatigue. At follow-up,
      demands did not add to the variance already explained by resources, and vice
      versa. Factors that contribute to the patient's physical condition before
      starting radiotherapy and to his/her perception of burden need to be addressed to
      further our understanding of their fatigue.

PMID- 9776374
TI  - Hypnotically induced control of nausea: a preliminary report.

PMID- 9776375
TI  - Chemopreventive agents: selenium.
AB  - The element selenium (Se) was recognized only 40 years ago as being essential in
      the nutrition of animals and humans. It is recognized as being an essential
      component of a number of enzymes, in which it is present as the amino acid
      selenocysteine. Se compounds have also been found to inhibit tumorigenesis in a
      variety of animal models, and recent studies indicate that supplemental Se in
      human diets may reduce cancer risk. The antitumorigenic activities have been
      associated with Se intakes that correct nutritionally deficient status in
      animals, as well as higher intakes that are substantially greater than those
      associated with maximal expression of the selenocysteine-containing enzymes.
      Therefore, it is proposed that while some cancer protection, particularly that
      involving antioxidant protection, involves selenoenzymes, specific Se
      metabolites, which are produced in significant amounts at relatively high Se
      intakes, also discharge antitumorigenic functions. According to this two-stage
      model of the roles of Se in cancer prevention, individuals with nutritionally
      adequate Se intakes may benefit from Se supplementation. Evidence for
      chemoprevention by Se and for the apparent mechanisms underlying these effects is
      reviewed to the end of facilitating the development of the potential of Se
      compounds as cancer chemopreventive agents.

PMID- 9776376
TI  - The renal excretory mechanisms and the role of organic cations in modulating the
      renal handling of paraquat.
AB  - Paraquat (PQ), a cationic herbicide, is predominantly excreted by the kidneys,
      but it is also nephrotoxic. It is thought to cause damage to proximal renal
      epithelial cells, which results in acute renal failure. The precise mechanism by
      which PQ is excreted by the kidney has not been fully elucidated, although
      current evidence indicates that it is actively secreted via a cation transport
      system. This review examines the renal cytotoxic effect and excretory mechanisms
      of PQ, and the role of organic cations in modulating the renal handling of PQ.

PMID- 9776377
TI  - Lipid-lowering drugs in the management of hyperlipidaemia.
AB  - Despite intense debate on the benefits of cholesterol lowering, the use of lipid
      lowering drugs has risen substantially in most countries. This change in attitude
      has accompanied the appreciation of data from initial observational studies on
      large cohorts that established the link between elevated serum cholesterol and
      coronary heart disease and randomized controlled trials of cholesterol lowering
      that demonstrated improvements in coronary morbidity and mortality seen in
      patients with or without coronary heart disease. Data are now accumulating on the
      effects of lowering serum triglyceride levels in improving coronary risk. More
      studies are still required, but metabolic studies indicate that high serum
      triglycerides are a marker for the presence of atherogenic small dense low
      density lipoproteins. Low concentrations of high-density lipoprotein cholesterol
      is also a marker for coronary risk, but the case for increasing levels by drugs
      is unclear. The rationale for the use of lipid-lowering drugs becomes more
      evident with an understanding of the mechanisms that cause hyperlipidaemia. In
      addition to serum lipid values, a good clinical history and examination are an
      essential part of assessing coronary risk. Certain groups, such as women,
      children, elderly people and patients with genetic hyperlipidaemias or liver or
      renal disease, need a special approach to therapy. The better tolerability and
      widespread use of the newer lipid-lowering drugs have raised issues of cost
      effectiveness. New lipid-lowering drugs are being developed, and there is some
      evidence that existing lipid-lowering drugs may produce benefit beyond that
      related to lipid lowering.

PMID- 9776378
TI  - 5-Hydroxytryptamine2-family receptors (5-hydroxytryptamine2A, 5
      hydroxytryptamine2B, 5-hydroxytryptamine2C): where structure meets function.
AB  - 5-Hydroxytryptamine2 (serotonin2, 5-HT2)-family receptors are important for
      mediating many physiological functions, including vascular and nonvascular smooth
      muscle contraction, platelet aggregation, modulation of perception, mood,
      anxiety, and feeding behavior. A large number of psychopharmaceuticals, including
      atypical antipsychotic drugs, antidepressants, anxiolytics, and hallucinogens,
      mediate their actions, at least in part, via interactions with various 5-HT2
      family receptors. This review article summarizes information about structure
      function aspects of 5-HT2-family receptors. Evidence is presented that implies
      that conserved aromatic and charged residues are essential for ligand binding to
      5-HT2A receptors. Additionally, findings are reviewed that are consistent with
      the hypothesis that residues located in intracellular loops 2 and 3 (i2 and i3)
      mediate coupling to specific G(alpha)-subunits such as G(alpha q). Studies are
      reviewed that suggest that 5-HT2-family receptors may be down-regulated by both
      agonists and antagonists, and usually this down-regulation is due to post
      transcriptional mechanisms. Finally, a model for regulation of 5-HT2-family
      receptors by receptor-mediated endocytosis is advanced, and the particular
      structural features responsible for the various endocytotic pathways are
      emphasized. Taken together, these results suggest that discrete domains of the
      receptor structure are important for ligand binding, G-protein coupling, and
      internalization.

PMID- 9776379
TI  - Functional coupling of human metabotropic glutamate receptor hmGlu1d: comparison
      to splice variants hmGlu1a and -1b.
AB  - Functional coupling of the human mGlu1 splice variants was examined by
      heterologous expression. In cells stably (CHO) or transiently (A9) expressing the
      hmGlu1d receptor. agonists elevated intracellular calcium with a rank order of
      potency typical of a group I mGlu receptor (quisqualate > L-glutamate > (S)
      dihydroxyphenylglycine > (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R
      ACPD)). These responses were reduced by the antagonist (+)-alpha-methyl-4
      carboxyphenylglycine (MCPG), by pretreatment with pertussis toxin and phorbol
      ester, and by removal of extracellular calcium. In transiently transfected HEK293
      cells, the hmGlu1b and -1d receptors increased inositol monophosphate (IP)
      production only in the presence of glutamate, whereas hmGlu1a coupled even in the
      absence of agonist. This was not due to differences in receptor expression levels
      as assessed by immunoblotting. Adenylate cyclase activity in HEK293 cells
      expressing the hmGlu1 variants was neither stimulated nor inhibited by glutamate.
      In A9 cells hmGlu1a-mediated calcium/fluo-3 fluorescence was sensitive to
      depletion of intracellular calcium stores by thapsigargin, but the hmGlu1d
      response was resistant. Thus, hmGlu1d receptors can be distinguished from hmGlu1a
      by their lack of agonist-independent coupling and their dependence on
      extracellular calcium.

PMID- 9776380
TI  - Substituted quinolines as inhibitors of L-glutamate transport into synaptic
      vesicles.
AB  - This study investigated the structure-activity relationships and kinetic
      properties of a library of kynurenate analogues as inhibitors of 3H-L-glutamate
      transport into rat forebrain synaptic vesicles. The lack of inhibitory activity
      observed with the majority of the monocyclic pyridine derivatives suggested that
      the second aromatic ring of the quinoline-based compounds played a significant
      role in binding to the transporter. A total of two kynurenate derivatives,
      xanthurenate and 7-chloro-kynurenate, differing only in the carbocyclic ring
      substituents, were identified as potent competitive inhibitors, exhibiting Ki
      values of 0.19 and 0.59 mM, respectively. The Km value for L-glutamate was found
      to be 2.46 mM. Parallel experiments demonstrated that while none of the
      kynurenate analogues tested effectively inhibited the synaptosomal transport of
      3H-D-aspartate, some cross-reactivity was observed with the EAA ionotropic
      receptors. Molecular modeling studies were carried out with the identified
      inhibitors and glutamate in an attempt to preliminarily define the pharmacophore
      of the vesicular transporter. It is hypothesized that the ability of the
      kynurenate analogues to bind to the transporter may be tied to the capacity of
      the quinoline carbocyclic ring to mimic the negative charge of the gamma
      carboxylate of glutamate. A total of two low energy solution conformers of
      glutamate were identified that exhibited marked functional group overlap with the
      most potent inhibitor, xanthurenate. These results help to further refine the
      pharmacological specificity of the glutamate binding site on the vesicular
      transporter and identify a series of inhibitors with which to investigate
      transporter function.

PMID- 9776381
TI  - Nicotine prevents glutamate-induced proteolysis of the microtubule-associated
      protein MAP-2 and glutamate neurotoxicity in primary cultures of cerebellar
      neurons.
AB  - The aim of this work was to assess whether nicotine prevents glutamate
      neurotoxicity in primary cultures of cerebellar neurons, to try to identify the
      receptor mediating the protective effect and to shed light on the step of the
      neurotoxic process which is prevented by nicotine. It is shown that nicotine
      prevents glutamate and NMDA neurotoxicity in primary cultures of cerebellar
      neurons. The protective effect of nicotine is not prevented by atropine,
      mecamylamine or dihydro-beta-erythroidine, but is slightly prevented by
      hexamethonium and completely prevented by tubocurarine and alpha-bungarotoxin,
      indicating that the protective effect is mediated by activation of alpha7
      neuronal nicotinic receptors. Moreover, alpha-bungarotoxin potentiates glutamate
      neurotoxicity, suggesting a tonic prevention of glutamate neurotoxicity by basal
      activation of nicotinic receptors. Nicotine did not prevent glutamate-induced
      rise of free intracellular calcium nor depletion of ATP. Nicotine prevents
      glutamate-induced proteolysis of the microtubule-associated protein MAP-2 and
      disaggregation of the neuronal microtubular network. The possible mechanism
      responsible for this prevention is discussed.

PMID- 9776382
TI  - Properties of GABA(A) receptors in cultured rat oligodendrocyte progenitor cells.
AB  - We have studied the properties of GABA responses in oligodendrocyte-type 2
      astrocyte (O-2A) progenitor cells derived from primary cultures of the neonatal
      rat brain. In whole cell voltage clamp recordings, rapid application of 1-10 mM
      GABA elicited current responses in > 85% of the cells examined. The dose-response
      relationship pooled from nine progenitor cells was best fit by a logistic
      function of EC50=113 microM and Hill coefficient=0.9. In contrast to the rate of
      current deactivation, the rate of current activation exhibited marked
      concentration-dependence. Pharmacologically, GABA, muscimol and ZAPA ((Z)
      3[(aminiiminomethyl)thio]prop-2-enoic acid sulphate) produced responses with
      ligand-specific kinetics, whereas glycine and the GABA(C) receptor agonist CACA
      were without effect; bicuculline methochloride acted as a competitive antagonist.
      Neither the amplitude nor the kinetics of currents produced by 100 microM GABA
      were affected by the benzodiazepine flunitrazepam (1 microM). Similarly the
      benzodiazepine receptor inverse agonist DMCM (1 microM) was also without effect.
      GABA-activated currents reversed polarity within 2 mV of the calculated Cl-
      equilibrium potential. With brief agonist pulses deactivation was
      monoexponential, however, unlike neurones the rate of deactivation was voltage
      independent. Desensitisation of responses to 10 mM GABA was bi-exponential and
      accelerated at depolarised membrane potentials. Increasing the amount of GABA(A)
      receptor desensitisation (by increasing the duration of the agonist exposure)
      consistently produced a slowing of deactivation.

PMID- 9776383
TI  - Evidence that P2X purinoceptors mediate the excitatory effects of
      alphabetamethylene-ADP in rat locus coeruleus neurones.
AB  - Extracellular and whole-cell patch clamp recordings were used to study the
      excitatory responses elicited by purine nucleotides in pontine slices of the rat
      brain containing the locus coeruleus (LC). The P2 purinoceptor agonists,
      alphabeta-methyleneadenosine 5'-triphosphate (alphabetameATP) and adenosine 5'-O
      (2-thiodiphosphate) (ADPalphabetaS), and a novel purinoceptor agonist, alphabeta
      methyleneadenosine 5'-diphosphate (alphabetameADP), elicited concentration
      dependent increases in the spontaneous firing rate over the concentration range
      (1-300 microM). On vagus nerve or dorsal root preparations alphabetameADP (100
      microM) had no agonist activity. In the presence of both alphabetameATP (300
      microM), ADPbetaS (300 microM) elicited a further and significant increase in the
      firing rate of the LC neurones, whilst neither alphabetameATP nor alphabetameADP
      (300 microM) elicited a further response. The P2 purinoceptor antagonists,
      suramin (100 microM) and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid
      (PPADS; 30 microM), markedly attenuated responses to all three agonists. Whole
      cell recording of membrane current showed that, at - 60 mV, alphabetameATP and
      alphabetameADP (both 100 microM) elicited inward currents of a similar magnitude,
      whilst the inward currents elicited by a lower concentration of ADPbetaS (30
      microM) were larger and faded in the presence of this agonist. In the presence of
      tetrodotoxin and a combination of other neurotransmission blockers, both
      alphabetameATP and alphabetameADP still produced inward currents. Based on the
      known selectivity of the agonists used in this study, there appear to be two
      distinct P2 purinoceptor types present on neurones in the LC, which correspond to
      the P2X and P2Y types. The responses elicited by alphabetameADP appear to be
      mediated through a putative P2X purinoceptor, although further work is required
      to determine which P2X receptor subtype(s) are involved.

PMID- 9776384
TI  - Naloxone-induced supersensitivity of oxytocin neurones to opioid antagonists.
AB  - Here we report that a single administration of naloxone to conscious rats
      produces no significant increase in oxytocin release, but when repeated 3-4 days
      later results in a large release of oxytocin. Plasma oxytocin concentrations were
      measured in conscious and urethane-anaesthetized rats pretreated with naloxone or
      isotonic saline on Day 1. On Days 2, 3 or 4, a second dose of naloxone was given,
      producing an increase in oxytocin secretion in naloxone-pretreated groups (P <
      0.05 vs. controls) on Day 3 and 4, but not on Day 2. The specificity of the
      opioid antagonist supersensitivity was determined by injection of the kappa
      antagonist nor-binaltorphimine (nor-BNI). Pretreated rats (naloxone, saline or
      nor-BNI, Day 1) received an additional acute nor-BNI injection (Day 4) which
      increased plasma oxytocin concentration in the three groups. However, this
      increase was higher in naloxone-pretreated rats with no differences between the
      nor-BNI- and saline-pretreated animals. Measurements of electrical activity of
      single supraoptic nucleus oxytocin neurons and of plasma oxytocin concentration
      (Day 4) showed that naloxone modestly enhanced the responsiveness of oxytocin
      neurons to cholecystokinin (CCK) in naloxone-pretreated rats (by comparison with
      saline-pretreated rats), but had only a small effect on basal firing rate that
      did not differ between naloxone-pretreated rats and saline-pretreated rats. To
      investigate whether naloxone-pretreatment modified the effect of morphine on CCK
      induced oxytocin release, on Day 4 CCK was injected i.v. with or without
      morphine. Morphine at a dose of 0.1 mg/kg did not affect CCK-induced oxytocin
      release, whereas 1 mg/kg of morphine blocked this release in both saline- and
      naloxone-pretreated rats. The results suggest that naloxone induces opioid
      antagonist supersensitivity on oxytocin secretion, mainly by up-regulating kappa
      opioid mechanisms on oxytocin nerve terminals in the posterior pituitary.

PMID- 9776385
TI  - The nitric oxide synthase inhibitor 7-nitroindazole displays enhanced anxiolytic
      efficacy without tolerance in rats following subchronic administration.
AB  - The nitric oxide synthase inhibitor 7-nitroindazole (7-NI) dose-dependently (3.0
      30.0 mg/kg) displayed anxiolytic activity, as measured by an increase in open arm
      exploration time in the elevated plus-maze (EPM), following intraperitoneal
      (i.p.) administration in rats. Acute administration of 7-NI at 30.0 mg/kg
      significantly (P < 0.05) increased open arm exploration time by 176% compared to
      vehicle control, similar to the benzodiazepine diazepam at 1.0 and 3.0 mg/kg (+
      191 and + 200%, respectively). However, 39 h following subchronic 5-day
      administration of diazepam twice daily (bid) at 3.0 mg/kg, diazepam was devoid of
      anxiolytic activity at 1.0 mg/kg, as measured by no difference in open arm
      exploration time compared to vehicle control, while the 3.0 mg/kg dose still
      produced a significant (P < 0.05) 175% increase in open arm exploration time. In
      contrast, following subchronic administration of 7-NI (30.0 mg/kg, bid), a
      significant (P < 0.01) enhancement in open arm exploration time was observed at
      30.0 mg/kg (+ 665% compared to control). Therefore, inhibition of nitric oxide
      synthase by 7-NI resulted in anxiolysis similar to diazepam following acute
      administration in the EPM. However, following subchronic administration, unlike
      diazepam which showed an attenuation of anxiolytic activity, 7-NI displayed
      enhanced anxiolytic efficacy and was devoid of tolerance.

PMID- 9776386
TI  - Effect of acute, short- and long-term milnacipran administration on rat locus
      coeruleus noradrenergic and dorsal raphe serotonergic neurons.
AB  - The effect of milnacipran on the firing activity of dorsal raphe serotonin (5-HT)
      neurons and locus coeruleus norepineprine (NE) neurons was assessed using
      extracellular unitary recording in chloral hydrate anesthetized rats. A 2-day
      treatment with milnacipran (20 or 60 mg/kg/day, s.c.) markedly decreased the
      firing rate of NE neurons, and it remained reduced after a 7- or a 14-day
      treatment. Although the suppressant effect of the alpha2-adrenergic agonist
      clonidine on the firing rate of NE neurons was markedly reduced following long
      term milnacipran (60 mg/kg/day x 14 days, s.c.), that of NE remained unchanged.
      The firing rate of 5-HT neurons was reduced following a 2-day treatment with
      milnacipran (20 mg/kg/day, s.c.), but there was a partial recovery after a 7-day
      treatment (20 mg/kg/day, s.c.) and a complete one after a 14-day treatment (20,
      40 or 60 mg/kg/day, s.c.). The suppressant effect of 5-HT and of the 5-HT1A
      agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) on the firing rate of
      5-HT neurons was also unaltered after milnacipran (60 mg/kg/day x 14 days, s.c.).
      The latter milnacipran treatment did not affect the uptake of [3H]5-HT but it
      inhibited that of [3H]NE by 30% in hippocampal slices. The NE system was thus
      investigated in an attempt to explain the effects of milnacipran on the firing
      activity of 5-HT neurons. Acute injection of milnacipran suppressed the firing
      activity of 5-HT neurons (with an ED50 of 5.7+/-1.5 mg/kg, i.v.), but not in NE
      denervated rats. Furthermore, the inhibitory effect of clonidine on 5-HT neuron
      firing activity was markedly reduced by the long-term milnacipran treatment,
      whereas the inhibition of electrically evoked release of [3H]NE as well as that
      of [3H]5-HT produced by the alpha2-adrenoceptor agonist UK 14.304 from preloaded
      mesencephalic slices containing the dorsal raphe was unaltered. The latter
      results indicate that the alpha2-adrenergic autoreceptor and heteroreceptor were
      unaffected in the raphe area by milnacipran. In conclusion, milnacipran had
      profound effects on the function of 5-HT and NE neurons, and the mechanism by
      which 5-HT neurons regained their normal firing during milnacipran treatment
      appeared to implicate the NE system.

PMID- 9776387
TI  - The relationship between the degree of neurodegeneration of rat brain 5-HT nerve
      terminals and the dose and frequency of administration of MDMA ('ecstasy').
AB  - The effect of varying the dose and frequency of administration of 3,4
      methylenedioxymethamphetamine (MDMA or 'ecstasy') on both the acute hyperthermic
      response and the long term neurodegeneration of 5-hydroxytryptamine (5-HT) nerve
      terminals in the brain has been studied in Dark Agouti rats. A single injection
      (4-15 mg/kg i.p.) of MDMA produced immediate dose-related hyperthermia and a dose
      related decrease in 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) and [3H]paroxetine
      binding in regions of the brain 7 days later, with a dose of 4 mg/kg having no
      degenerative effect. This dose was also without effect when given once daily for
      4 days, but produced a marked loss of [3H]paroxetine binding and indole
      concentration ( approximately 55%) when given twice daily for 4 days. When a dose
      of 4 mg/kg was given twice weekly for 8 weeks it had no effect on these
      serotoninergic markers, despite a clear anorectic effect of the drug being seen.
      These data demonstrate that MDMA-induced neurodegeneration is related to both the
      dose and frequency of administration and indicate that damage to 5-HT neurones
      can occur in the absence of a hyperthermic response to the drug. We suggest that
      damage occurs when endogenous free radical scavenging mechanisms become
      overwhelmed or exhausted.

PMID- 9776388
TI  - Behavioral effects of phenelzine in an experimental model for screening
      anxiolytic and anti-panic drugs: correlation with changes in monoamine-oxidase
      activity and monoamine levels.
AB  - This study investigated the effects of acute and chronic (one daily i.p.
      injection for 14 days) treatments with the non-selective irreversible monoamine
      oxidase (MAO) inhibitor phenelzine (10 and 30 mg/kg) on defensive behaviors of
      Swiss mice in the mouse defense test battery (MDTB) which has been designed for
      screening anxiolytic and anti-panic drugs. In the MDTB, subjects were confronted
      with a natural threat (a rat) and situations associated with this threat. MAO-A
      and MAO-B activities and levels of brain monoamines (serotonin (5-HT), dopamine
      (DA) and norepinephrine (NE)) and their deaminated metabolites were subsequently
      measured. Behavioral results showed that acute administration of phenelzine did
      not specifically modify defensive behaviors. By contrast, after chronic
      treatment, phenelzine produced a significant reduction in avoidance distance when
      the rat was approaching, an effect which is consistent with an anti-panic-like
      action. In addition, phenelzine displayed weak anxiolytic-like effects as it
      increased risk assessment responses when mice were constrained in one part of the
      apparatus facing the rat which remained at a constant distance. No other specific
      drug effect was observed. These behavioral changes were associated with a
      dramatic increase in 5-HT levels, in particular after chronic treatment, while
      levels of DA and NE increased only slightly. Importantly, no significant
      differences in DA and NE levels between acute and chronic regimens were observed.
      Levels of deaminated metabolites of monoamines were markedly decreased.
      Measurements of MAO activity revealed substantial reductions in both type A and B
      forms with a full inhibition of both forms being observed only after chronic
      treatment with phenelzine. These results suggest that the effects of phenelzine
      may be due mainly to its effects on the 5-HT system and presumably related to the
      full inhibition of MAO-A and/or MAO-B.

PMID- 9776389
TI  - Elevation of extracellular cortical noradrenaline may contribute to the
      antidepressant activity of zotepine: an in vivo microdialysis study in freely
      moving rats.
AB  - The antipsychotic, zotepine, as well as possessing affinity for dopamine D1- and
      D2-1ike receptors, has high affinity for the noradrenaline (NA) transporter and
      inhibits [3H]NA uptake by rat frontal cortex synaptosomes, in vitro. The present
      studies investigated the effects of zotepine on extracellular NA in the frontal
      cortex of freely moving rats using in vivo microdialysis. Removal of calcium from
      the perfusate reduced extracellular NA by 70.5% and prevented the 50 mM KCl
      stimulated increase in NA levels. Zotepine (0.5-1.5 mg kg(-1) i.p.), evoked
      biphasic, dose-dependent rises in extracellular NA with maximal increases
      observed at 60 min (+ 171.0%) and 240 min (+ 211.5%) post-treatment. The
      increases in NA levels were sustained for up to 100 min post-dosing. Clozapine
      (10.0 mg kg(-1) i.p.), resulted in a smaller, transient increase in NA levels (+
      72.0%) which lasted for 20 min post-treatment. Neither ziprasidone (3.0 mg kg(-1)
      i.p.) nor olanzapine (1.0 mg kg(-1) i.p.) influenced extracellular NA. Systemic
      treatment with the antidepressant desipramine (0.3 mg kg(-1) i.p.) resulted in a
      prolonged elevation of NA levels over 240 min (maximal increase of + 354.3%),
      whilst local infusion of nisoxetine (1-100 microM) through the dialysis probe
      increased NA levels in a concentration-dependent manner (up to 587.8% of control
      values). These data suggest that the inhibition of NA uptake by zotepine and its
      subsequent prolonged elevation of extracellular cortical NA may underlie the
      reported antidepressant properties of zotepine in schizophrenic patients.

PMID- 9776390
TI  - Investigation of the presynaptic effects of quinine and quinidine on the release
      and uptake of monoamines in rat brain tissue.
AB  - Quinine and quinidine are reported to potentiate the behavioural effects of
      serotonergic agents and monoamine uptake inhibitors. We have therefore
      investigated the presynaptic actions of quinine and quinidine on monoamine uptake
      and release in rat brain tissue in vitro. Quinidine evoked the release of [3H]5
      HT, [3H]noradrenaline and [3H]dopamine from pre-loaded rat brain slices in a
      concentration dependent manner with EC50 values of 175, 486 and 150 microM,
      respectively. Quinine induced [3H]monoamine release with similar potencies. Both
      quinine and quinidine also inhibited the active uptake of [3H]5-HT,
      [3H]noradrenaline and [3H]dopamine into rat brain synaptosomes with IC50 values
      in the range 0.13-12.4 microM. The potency of each drug to inhibit [3H]5-HT
      uptake was significantly higher than that for [3H]noradrenaline or [3H]dopamine.
      The relative potency of quinidine compared to quinine was more marked in the case
      of [3H]5-HT (58-fold) than for [3H]noradrenaline (3-fold) or [3H]dopamine (4
      fold). The inhibition of [3H]5-HT uptake by quinine and quinidine was competitive
      in nature and corresponded with the potencies of these drugs to inhibit
      [3H]paroxetine binding. No correlation was observed between the potencies of
      quinine and quinidine to induce the release of [3H]monoamines and to inhibit
      their uptake, suggesting that these effects are mediated by two distinct
      mechanisms. We conclude that the presynaptic actions of quinine and quinidine on
      monoamine uptake and release may be implicated in their potentiation of the
      effects of serotonergic agents and uptake blockers.

PMID- 9776391
TI  - Serotonin (5-HT)2C receptors tonically inhibit dopamine (DA) and noradrenaline
      (NA), but not 5-HT, release in the frontal cortex in vivo.
AB  - The novel, preferential 5-HT2C receptor agonist, Ro 60-0175 ((S)-2-(6-chloro-5
      fluoroindol-1-yl)-1-methylethylamine) (2.5 mg,kg, s.c.), markedly suppressed
      dialysate levels of dopamine (DA) and noradrenaline (NA) levels in the frontal
      cortex of freely-moving rats without affecting levels of 5-HT. In contrast, the
      novel and selective 5-HT2C receptor antagonist, SB-242084 (6-chloro-5-methyl-1-[6
      (2-methylpyridin-3-yloxy) pyridin-3-yl carbamoyl] indoline) (10.0 mg/kg, i.p.),
      markedly increased dialysate levels of DA and NA without modifying those of 5-HT.
      These data suggest that 5-HT2C receptors exert a tonic, inhibitory influence upon
      frontocortical dopaminergic and adrenergic, but not serotonergic, transmission.

PMID- 9776392
TI  - Chemical and immunological characterization of a low molecular weight outer
      membrane protein of Salmonella typhi.
AB  - A new immunogenic outer membrane protein, Omp-28 (MW 28,000 and pI 4.6), was
      isolated from smooth Salmonella typhi cells by the use of an extracting medium
      containing 6 M urea, 1% deoxycholate and 5 mM EDTA. The purification of Omp-28
      was performed by gel filtration and fast ion exchange chromatography. This
      protein showed to be the prevalent component isolated by the latter methodology.
      Omp-28 is formed by three identical subunits (MW 9,000), not linked by disulfide
      bonds. The partial N-terminal amino acid sequence of Omp-28 presented great
      homology with part of the sequence of an Escherichia coli protein found in a
      precursor whose sequence was predicted by c-DNA. ELISA and Western blotting
      identified Omp-28 as the major antigenic protein present in the outer membrane
      protein fraction, isolated by gel filtration. Antibodies against Omp-28 were
      detected by ELISA in 43% of 28 sera from typhoid fever convalescent patients. The
      antisera from mice immunized with Omp-28 and the highest positive typhoid fever
      convalescent serum gave a positive bactericidal test, killing 50% of Salmonella
      typhi cells in serum dilutions of 1/80 and 1/320, respectively. These results
      indicate the immunogenic importance of Omp-28 isolated from Salmonella typhi
      outer membrane and strongly suggest it should be used in further studies of
      animal protection against the disease caused by this pathogenic bacteria.

PMID- 9776393
TI  - Heterogeneity in expression of lipopolysaccharide and major outer-membrane
      proteins by strains of Escherichia coli O157 with different H-serotypes.
AB  - A total of 11 strains of Escherichia coli (E. coli) belonging to serogroup O157
      were examined for the expression of long-chain lipopolysaccharide (LPS) and major
      outer-membrane proteins (OMPs) by means of SDS-PAGE. The strains belonged to
      either one of four different flagellar (H) types or did not express flagella.
      Four of the eleven strains carried genes encoding Shiga-like toxins (SLTs). All
      the strains exhibited one of four LPS profiles, designated A, B, C or D. Electron
      microscopic analysis with the freeze-substitution technique demonstrated the
      differences in the cell surface structures of strains with each LPS profile.
      Strains with LPS profile A, B or C had layers of thin fibers 10, 20 and 20 nm
      long, respectively, on the outer membrane but strains with LPS profile D had no
      such structure. An analysis of the OMPs showed that all the strains had one of
      four OMP profiles, designated I, II, III or IV. Both LPS and OMP profiles were
      dependent on H-serotypes, and the combination pattern of LPS and OMP profiles of
      the strains was unique for each H-serotype. These data support the existence of
      heterogeneous groups of O157 strains.

PMID- 9776394
TI  - Mechanism of membrane damage by Clostridium perfringens alpha-toxin.
AB  - The effect of Clostridium perfringens alpha-toxin on liposomes prepared from
      phosphatidylcholine (PC) containing the fatty acyl residues of 18 carbon atoms
      was investigated. The toxin-induced carboxyfluorescein (CF) leakage and
      phosphorylcholine release from multilamellar liposomes increased as the phase
      transition temperature of the phosphatidylcholines containing unsaturated fatty
      acyl residues decreased. However, there was no difference between the sensitivity
      of the different phosphatidylcholines solubilized by deoxycholate to the
      phospholipase C (PLC) activity of the toxin. However, the toxin did not hydrolyze
      solubilized distearoyl-L-alpha-phosphatidylcholine (DSPC) or phosphatidylcholine
      containing saturated fatty acyl residue, and caused no effect on liposomes
      composed of DSPC. These results suggest that the activity of the toxin is closely
      related to the membrane fluidity and double bond in PC. The N-terminal domain of
      alpha-toxin (AT1-246) and variant H148G did not induce CF leakage from liposomes
      composed of dioleoyl-L-alpha-phosphatidylcholine (DOPC). H148G bound to the
      liposomes, but AT1-246 did not. However, the C-terminal domain (AT251-370)
      conferred binding to liposomes and the membrane-damaging activity on AT1-246.
      These observations suggest that the membrane-damaging action of alpha-toxin is
      due to the binding of the C-terminal domain of the toxin to the double bond in
      the PC in the bilayer and hydrolysis of the PC by the N-terminal domain.

PMID- 9776395
TI  - Determination of serotypes of astroviruses by reverse transcription-polymerase
      chain reaction and homologies of the types by the sequencing of Japanese
      isolates.
AB  - Human standard astroviruses, serotypes 1 to 7, and 35 Japanese isolates were
      typed by reverse transcription and polymerase chain reaction (RT-PCR) with
      serotype-specific primers for the first time. The results were identical with
      those obtained by enzyme immunoassay with serotype-specific polyclonal
      antibodies, a method which has already been reported. RT-PCR with serotype
      specific primers is useful for epidemiological studies of astroviruses where
      serotype-specific polyclonal antibodies are not available. Two parts of the
      capsid region, N terminus and C terminus, were sequenced. Serotypes differed in
      those regions. The N terminus differed less than the C terminus between
      serotypes. Both the N terminus and C terminus were similar intraserotypically
      with the exception of serotype-4 isolates which could be divided into A and B
      subgroups on the basis of their C terminus sequences, which were not known
      previously.

PMID- 9776396
TI  - Single-step reverse transcription-polymerase chain reaction for the detection of
      hepatitis C virus RNA.
AB  - We developed a novel single-step reverse transcription-polymerase chain reaction
      (RT-PCR), which is equal in sensitivity and specificity to RT-nested PCR, based
      on both reverse transcriptase and Taq DNA polymerase working efficiently under
      single buffer reaction conditions. Using in vitro synthesized hepatitis C virus
      (HCV) RNA, it was demonstrated that 10-100 copies of HCV RNA could be detected
      with a set of primers that amplify a 144 base-pair sequence unique to the 5'
      noncoding region of HCV RNA. Furthermore, this method was successfully performed
      on serum and liver biopsy specimens obtained from patients with chronic hepatitis
      C. In addition, HCV RNA from in vitro HCV-infected MT-2C cells, which supported
      HCV replication, was also detected by this method. The method is anticipated to
      improve the detection of small amounts of RNA, such as that of HCV, promoting
      both labor savings and the prevention of carry-over contamination.

PMID- 9776397
TI  - The functional role of B7 molecules on the induction of thymocyte activation and
      apoptosis.
AB  - To evaluate the role of B7 on thymocyte activation and apoptosis, we took
      advantage of TCR transgenic mice in which the majority of thymocytes express a
      uniform TCR that is specific for ovalbumin. We also prepared Chinese hamster
      ovary (CHO) cells expressing B7 and appropriate class II molecules. We found that
      the apoptosis of double-positive thymocytes by TCR-mediated signaling, which
      presumably represents negative selection, requires a costimulatory signal
      provided by B7-1 or B7-2. The requirement of B7-1 costimulation for the apoptosis
      of thymocytes does not change in either low or high antigenic peptide loading. We
      also demonstrated that two signals through TCR and CD28 augmented the
      proliferation of thymocytes, and the requirement of CD28-mediated signal by B7-1
      or B7-2 for thymocyte proliferation became less evident when high doses of
      antigenic peptide were loaded, indicating that the intensity of TCR-mediated
      signal determines the requirement of B7-mediated second signal for thymocyte
      proliferation.

PMID- 9776398
TI  - Induction of apoptosis and tyrosine phosphorylation of cellular proteins in T
      cells and non-T cells by stimulation with concanavalin A.
AB  - A high concentration (30 microg/ml or more) of Con A caused the death of not only
      thymocytes but also splenic cells of BALB/c mice, whereas a moderate
      concentration (3 microg/ml) of Con A induced proliferation of these cells. A high
      concentration of Con A also induced the death of splenic cells of athymic BALB/c
      nu/nu mice and the bone marrow cells of BALB/c mice which mainly consist of non-T
      cells. However, any concentration (1-30 microg/ml) of Con A failed to induce the
      proliferation of these cells. Specific binding of tetrameric Con A to mannose
      containing receptors was required for the induction of cell death. DNA
      fragmentation was observed by both laser flow cytometry and electrophoresis in
      Con A-stimulated T cells and non-T cells. This indicated that the mechanism of
      induction of apoptosis with Con A is not necessarily TCR-dependent. Con A induced
      tyrosine phosphorylation of a number of proteins in various types of cells.
      Interestingly, phosphorylation of the 40 kDa protein developed only in the
      thymocytes and spleen cells that contain T cells, whereas phosphorylation of the
      80 and 120 kDa proteins appeared in both T cells and non-T cells. These results
      suggested that the Con A-induced apoptosis of T cells and non-T cells involves
      different but possibly mutually related protein tyrosine phosphorylation-linked
      signals.

PMID- 9776399
TI  - The first isolation of Arthroderma benhamiae in Japan.
AB  - A clinical isolate of Trichophyton mentagrophytes from rabbit was examined by
      polymerase chain reaction (PCR) analysis and a mating experiment. The species
      specific primers designed from the nucleotide sequences of the chitin synthase 1
      (CHS1) gene in the teleomorph of Arthroderma benhamiae amplified a fragment from
      genomic DNA samples of A. benhamiae and the clinical isolate but not from those
      of A. simii and A. vanbreuseghemii. On the other hand, the species-specific
      primers of A. simii and A. vanbreuseghemii did not amplify any fragment from the
      genomic DNA of the clinical isolates. When the isolate was respectively crossed
      with (+) or (-) tester strains of A. benhamiae, A. simii and A. vanbreuseghemii,
      ascospores were produced in the crossing with the A. benhamiae (+) strain.
      Therefore, the isolate was identified to be A. benhamiae (-), confirming the
      result of molecular analysis. This is the first report on the isolation of A.
      benhamiae in Japan.

PMID- 9776400
TI  - Rapid analysis of allelic variants of the sheep PrP gene by oligonucleotide
      probes.
AB  - A rapid method to determine the allelic variants of the sheep PrP gene was
      developed. DNA samples from 128 Suffolk sheep (39 rams and 89 ewes) were screened
      by using polymerase chain reactions and dot-blot hybridization with 32P-labeled
      nine allele-specific oligonucleotide probes corresponding to the polymorphic PrP
      codons 112, 136, 154 and 171. Three allelic variants of the PrP gene, PrP(MARQ),
      PrP(TARQ) and PrP(MARR), were found in the flocks. Among those variants, nearly
      half of the ewes had alleles of the 171-Arg variant that is closely associated
      with resistance to natural scrapie. Assessments of allelic mutations of the PrP
      gene may help to select the scrapie-resistant progenitors in the flocks.

PMID- 9776402
TI  - The retinoblastoma-like protein family: still in the shadow of the RB gene?

PMID- 9776401
TI  - Passive smoking and lung cancer risk: what is the story now?

PMID- 9776404
TI  - The rise and fall of the front-page gene.

PMID- 9776403
TI  - How to slice it? Tissue technologies vie for potentially lucrative market.

PMID- 9776405
TI  - Cancer control efforts reach out to "culturally isolated" groups.

PMID- 9776406
TI  - Are lumpectomies for kidney cancer shifting towards acceptance?

PMID- 9776407
TI  - Tamoxifen debate hinges on whose risk is high enough.

PMID- 9776408
TI  - Benefits and risks of screening mammography for women in their forties: a
      statistical appraisal.

PMID- 9776409
TI  - Multicenter case-control study of exposure to environmental tobacco smoke and
      lung cancer in Europe.
AB  - BACKGROUND: An association between exposure to environmental tobacco smoke (ETS)
      and lung cancer risk has been suggested. To evaluate this possible association
      better, researchers need more precise estimates of risk, the relative
      contribution of different sources of ETS, and the effect of ETS exposure on
      different histologic types of lung cancer. To address these issues, we have
      conducted a case-control study of lung cancer and exposure to ETS in 12 centers
      from seven European countries. METHODS: A total of 650 patients with lung cancer
      and 1542 control subjects up to 74 years of age were interviewed about exposure
      to ETS. Neither case subjects nor control subjects had smoked more than 400
      cigarettes in their lifetime. RESULTS: ETS exposure during childhood was not
      associated with an increased risk of lung cancer (odds ratio [OR] for ever
      exposure = 0.78; 95% confidence interval [CI] = 0.64-0.96). The OR for ever
      exposure to spousal ETS was 1.16 (95% CI = 0.93-1.44). No clear dose-response
      relationship could be demonstrated for cumulative spousal ETS exposure. The OR
      for ever exposure to workplace ETS was 1.17 (95% CI = 0.94-1.45), with possible
      evidence of increasing risk for increasing duration of exposure. No increase in
      risk was detected in subjects whose exposure to spousal or workplace ETS ended
      more than 15 years earlier. Ever exposure to ETS from other sources was not
      associated with lung cancer risk. Risks from combined exposure to spousal and
      workplace ETS were higher for squamous cell carcinoma and small-cell carcinoma
      than for adenocarcinoma, but the differences were not statistically significant.
      CONCLUSIONS: Our results indicate no association between childhood exposure to
      ETS and lung cancer risk. We did find weak evidence of a dose-response
      relationship between risk of lung cancer and exposure to spousal and workplace
      ETS. There was no detectable risk after cessation of exposure.

PMID- 9776410
TI  - Retinoblastoma-related protein pRb2/p130 and suppression of tumor growth in vivo.
AB  - BACKGROUND: The RB/p105 and p107 genes of the retinoblastoma family are tumor
      suppressor genes whose proteins are inactivated by interaction with T-antigen
      proteins encoded by polyomaviruses (e.g., simian virus 40 and human JC virus),
      which have been found to be highly tumorigenic in animals. A variety of indirect
      evidence suggests that another member of the retinoblastoma gene family,
      RB2/p130, is also a tumor suppressor gene. To investigate the putative tumor
      suppressor activity of RB2/p130 more directly, we utilized a tetracycline
      regulated gene expression system to control expression of the encoded protein
      pRb2/p130 in JC virus-induced hamster brain tumor cells and to study the effects
      of pRb2/p130 on the growth of such tumor cells in nude mice. The ability of
      pRb2/p130 to interact with JC virus T antigen was also studied. METHODS: Northern
      blot hybridization analyses were performed on samples of total cellular RNA to
      measure RB2/p130 and beta-actin messenger RNA levels. Immunoprecipitation and
      western blot analyses were used to determine T-antigen and pRb2/p130 protein
      levels and to assess the phosphorylation status of these proteins. Tumor cells
      were injected subcutaneously into nude mice, and tumor growth, with or without
      induced expression of pRb2/p130, was monitored. RESULTS: Induction of pRb2/p130
      expression brought about a 3.2-fold, or 69% (95% confidence interval = 64%-73%),
      reduction in final tumor mass in nude mice. We also demonstrated that JC virus T
      antigen binds hypophosphorylated pRb2/p130 and that stimulation of pRb2/p130
      expression overcomes cellular transformation mediated by this antigen.
      CONCLUSION: Our findings support the hypothesis that RB2/p130 is a tumor
      suppressor gene.

PMID- 9776411
TI  - Biologic activity of tamoxifen at low doses in healthy women.
AB  - BACKGROUND: Results of a clinical trial recently completed in the United States
      indicate that administration of tamoxifen (20 mg/day) to women at risk can reduce
      breast cancer incidence by approximately 50% but is associated with an increased
      risk of developing endometrial cancer and venous thromboembolic events. Since
      these adverse effects may be dose related, we investigated the effect of
      tamoxifen on several biomarkers when the drug was given at doses lower than those
      currently in use. METHODS: In two sequential experiments, 127 healthy
      hysterectomized women aged 35-70 years were randomly assigned to one of the
      following four treatment arms: placebo (n = 31) or tamoxifen at 20 mg/day (n =
      30) (first experiment); or tamoxifen at 10 mg/day (n = 34) or tamoxifen at 10 mg/
      alternate days (n = 32) (second experiment). Baseline and 2-month measurements of
      the following parameters were compared: 1) total cholesterol (primary end point)
      and other surrogate markers of cardiovascular disease, e.g., low-density
      lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and
      lipoprotein(a); 2) blood cell count; 3) fibrinogen; 4) antithrombin III; 5)
      osteocalcin; and, 6) in a subgroup of 103 women, insulin-like growth factor-I
      (IGF-I), a possible surrogate marker for breast cancer. RESULTS: After adjustment
      for the baseline values, there were reductions in circulating levels of total
      cholesterol and IGF-I of the same magnitude in all three tamoxifen treatment
      arms. A similar pattern was observed for most of the other parameters. In the
      placebo arm, fibrinogen level, which showed a decrease, was the only parameter
      exhibiting change. CONCLUSIONS: Up to a 75% reduction in the conventional dose of
      tamoxifen (i.e., 20 mg/day) does not affect the activity of the drug on a large
      number of biomarkers, most of which are surrogate markers of cardiovascular
      disease. This study was hypothesis generating, and larger studies are warranted
      to assess the efficacy of tamoxifen at low doses.

PMID- 9776412
TI  - Relationship between serum concentrations of the growth factor pleiotrophin and
      pleiotrophin-positive tumors.
AB  - BACKGROUND: Growth factors produced by tumor cells are essential for tumor
      expansion and may be useful in monitoring tumor progression or therapeutic
      efficacy if the factors are released into the circulation. In this study, we
      measured serum levels of pleiotrophin, a secreted heparin-binding growth and
      angiogenesis factor, in mice bearing human tumor xenografts to determine whether
      these levels reflected overall tumor burden, and we examined the relationship
      between tumor expression of pleiotrophin and serum levels of this factor in
      patients with cancer. METHODS: Pleiotrophin in serum from mice and humans was
      measured by use of a highly sensitive enzyme-linked immunosorbent assay. For the
      clinical studies, serum specimens were obtained from 193 patients with various
      cancers of the gastrointestinal tract and from 28 healthy control subjects. In a
      subset of 64 cancer patients, serum levels of pleiotrophin were measured at the
      time of surgery, and tumor expression of this factor was detected
      immunohistochemically. All P values are two-sided. RESULTS: In mice, serum
      pleiotrophin levels were found to increase as a function of tumor size. In
      humans, elevated serum pleiotrophin levels were found in patients with pancreatic
      cancer (n = 41; P<.0001) and colon cancer (n = 65; P = .0079) but not in patients
      with stomach cancer (n = 87; P =.42). A statistically significant positive
      association was found between elevated levels of pleiotrophin in serum drawn at
      the time of surgery and expression of this factor by tumors (P<.0001). In both
      mice and humans, serum pleiotrophin levels dropped after successful tumor
      removal. CONCLUSIONS: Elevated serum pleiotrophin levels can indicate the
      presence of tumors expressing this factor. Monitoring serum levels of
      pleiotrophin may prove useful in determining the pharmacologic efficacy of
      cytotoxic or anti-pleiotrophin therapy.

PMID- 9776413
TI  - Specific genetic predictors of chemotherapeutic response and survival in patients
      with anaplastic oligodendrogliomas.
AB  - BACKGROUND/METHODS: Gliomas are common malignant neoplasms of the central nervous
      system. Among the major subtypes of gliomas, oligodendrogliomas are distinguished
      by their remarkable sensitivity to chemotherapy, with approximately two thirds of
      anaplastic (malignant) oligodendrogliomas responding dramatically to combination
      treatment with procarbazine, lomustine, and vincristine (termed PCV).
      Unfortunately, no clinical or pathologic feature of these tumors allows accurate
      prediction of their response to chemotherapy. Anaplastic oligodendrogliomas also
      are distinguished by a unique constellation of molecular genetic alterations,
      including coincident loss of chromosomal arms 1p and 19q in 50%-70% of tumors. We
      have hypothesized that these or other specific genetic changes might predict the
      response to chemotherapy and prognosis in patients with anaplastic
      oligodendrogliomas. Therefore, we have analyzed molecular genetic alterations
      involving chromosomes 1p, 10q, and 19q and the TP53 (on chromosome 17p) and
      CDKN2A (on chromosome 9p) genes, in addition to clinicopathologic features in 39
      patients with anaplastic oligodendrogliomas for whom chemotherapeutic response
      and survival could be assessed. RESULTS/CONCLUSIONS: Allelic loss (or loss of
      heterozygosity) of chromosome 1p is a statistically significant predictor of
      chemosensitivity, and combined loss involving chromosomes 1p and 19q is
      statistically significantly associated with both chemosensitivity and longer
      recurrence-free survival after chemotherapy. Moreover, in both univariate and
      multivariate analyses, losses involving both chromosomes 1p and 19q were strongly
      associated with longer overall survival, whereas CDKN2A gene deletions and ring
      enhancement (i.e., contrast enhancement forming a rim around the tumor) on
      neuroimaging were associated with a significantly worse prognosis. The inverse
      relationship between CDKN2A gene deletions and losses of chromosomes 1p and 19q
      further implies that these differential clinical behaviors reflect two
      independent genetic subtypes of anaplastic oligodendroglioma. These results
      suggest that molecular genetic analysis may aid therapeutic decisions and predict
      outcome in patients with anaplastic oligodendrogliomas.

PMID- 9776414
TI  - Evidence for an ontogenetic basis for circadian coordination of cancer cell
      proliferation.

PMID- 9776415
TI  - Re: Cigarette smoking and the histopathology of lung cancer.

PMID- 9776416
TI  - Diffuse thin glomerular basement membrane in association with idiopathic
      membranous glomerulonephritis.
AB  - Here we present a rare report of diffuse thin glomerular basement membrane
      (dTGBM) with idiopathic membranous glomerulonephritis (IMGN). dTGBM was found in
      11 (2.04%) of 539 adult patients with IMGN. The male:female ratio was 1:1.2.
      Sixty patients with IMGN alone (matched for age and sex) were adjusted and
      analyzed as control patients. There was no significant difference in the clinical
      and laboratory data between the two groups except for the microhematuria, which
      was more frequently found in the dTGBM associated IMGN group (dTGBM + IMGN)
      (10/11, 91%) than in the IMGN group (19/60, 31.7%), and the difference was
      significant (p <0.001). However, no statistical difference was found in
      morphological parameters between the two groups except in the thickness of the
      glomerular basement membrane (GBM). In this study, using specific monoclonal
      antibodies against the chains of type IV collagen, no change in quality or
      location (in aberrant or no expression) was found in the collagenous composition
      of the dTGBM compared to the normal GBM. No prominent thickening or
      transformation of the GBM, which is characteristic for MGN, developed in the
      dTGBM + IMGN cases or IMGN. As a result, we could not detect any difference in
      the prognosis between these two groups. These findings support the view that IMGN
      can occur in patients with dTGBM, and the dTGBM patients may recover completely.
      The possible coexistence of these diseases was thus hypothesized due to the
      persisting microhematuria.

PMID- 9776417
TI  - Recurrence of membranous nephropathy after renal transplantation: probability,
      outcome and risk factors.
AB  - Recurrence of membranous nephropathy after renal transplantation has been
      reported either anecdotally or in a few series. In the present study, the
      potential risk factors as well as hitherto unreported actuarial risk for
      recurrence and graft loss due to recurrence were evaluated by combining data of a
      series of transplanted patients with MN at Louvain Medical School (n = 12) and at
      Lyon (n = 18; previously reported by Couchoud et al. 1995) giving a total of 30
      patients. No risk factor for recurrence was identified as there was no
      statistical difference between the patients with and without recurrence for
      duration of MN in native kidneys or of pretransplant hemodialysis, presence of
      HLA-DR3, graft origin and use of cyclosporin. Actuarial risk for recurrence
      reached 29% at 3 years, plateauing up to 10 years. The outcome of recurrence was
      poor since the actual risk for graft loss among patients with recurrent MN was 38
      and 52% at 5 and 10 years, respectively.

PMID- 9776418
TI  - Analysis of renal pathology and drug history in 158 Japanese patients with
      rheumatoid arthritis.
AB  - To clarify the characteristics of renal pathology and its correlation with
      disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid
      arthritis (RA), renal biopsy findings from 158 Japanese RA patients with urinary
      abnormalities and/or renal dysfunction were analyzed retrospectively in the
      period between 1979 and 1996. Urologic abnormality and urinary tract infection
      were ruled out in all patients. Light and immunofluorescence (IF) microscopy were
      performed in all patients. Mesangial proliferative glomerulonephritis (MesPGN)
      was diagnosed in 54 patients, membranous nephropathy (MN) in 49, and secondary
      amyloidosis (AM) in 30. Renal dysfunction was more frequent in patients with AM
      (22/30) than in patients without (40/128). Forty of 49 MN patients developed
      renal disorders during DMARDs therapy. The prevalence of DMARD-related MN
      increased during the period of observation. The fact that DMARDs are of very
      frequent use in recent Japanese RA patients may reflect the prevalence of MN in
      this study. Two thirds of patients with MesPGN developed renal disorders when no
      DMARDs were used. One half of 54 MesPGN patients demonstrated IgA
      glomerulonephritis (GN) by IF. The prevalence of primary renal diseases in Japan
      may reflect the frequency of IgA GN in Japanese RA patients. Furthermore, diffuse
      thinning of the glomerular basement membrane (GBM) was observed in 30 of 81
      patients with electron microscopy. RA itself may underlie the pathogenesis of GBM
      thinning, and drugs used for RA treatment may also accelerate the development of
      this lesion. In conclusion, although MesPGN, MN, and AM may be relatively more
      common, IgA GN and GBM thinning also were other frequent entities in Japanese RA
      patients. No correlation was observed between DMARDs and renal disorders
      excepting MN.

PMID- 9776419
TI  - Effect of hypertension, diabetes and other cardiovascular risk factors on kidney
      size in middle-aged adults.
AB  - The aim of the study was to investigate in a population-based series (1031
      subjects, age range 40-60 years) whether the renal size of hypertensive subjects
      differs from that of control subjects and whether the difference might be due to
      hypertension itself or risk factors associated with hypertension. The renal
      measurements were performed by abdominal ultrasound. The genders were analyzed
      separately. Hypertensive men had slightly larger kidneys than controls (70.1+/
      8.9 cm2 vs. 67.9+/-8.7 cm2, p <0.008). The difference was, however, mediated
      mainly through the body mass index (BMI), whereas hypertension, blood pressure or
      hypertensive medication did not affect renal size. High serum concentrations of
      uric acid and creatinine were associated with smaller kidney size (p <0.001 and p
      <0.05, respectively). Alcohol users had slightly larger kidneys than abstainers,
      but the difference was not significant. Renal size increased with pack years of
      smoking. Diabetics had 4.8% larger kidneys (p <0.039), but no difference was
      observed between the subjects with impaired glucose tolerance and those with
      normal test results. In multivariate analysis, the most significant factors
      associated with enlarged kidney size were the fasting blood glucose concentration
      (p < or = 0.0001), smoking (p < or = 0.0001) and atherosclerotic lesions in
      carotid arteries (p <0.002). The kidneys were also slightly larger in
      hypertensive women than in control subjects, but the difference was only of
      borderline significance (p <0.08). Women on hormone replacement therapy had
      smaller kidneys than other women (p <0.05), but there was no difference in renal
      measures between premenopausal and postmenopausal women. In multivariate
      analysis, the most significant factors contributing to large kidney size were
      blood glucose concentration (p <0.0001) and smoking (p <0.05), while age and
      serum creatinine concentration were associated with smaller kidney size (p
      <0.0001 and p <0.0001). We conclude that renal size is related to sex and the
      subject's height and weight. Smoking, abnormal glucose tolerance, blood uric
      acid, creatinine, carotid atherosclerosis and hormone replacement therapy in
      women were also significant factors for renal size. Hypertensive subjects had
      larger kidneys than controls, mainly because of their more frequent obesity and
      abnormal glucose test.

PMID- 9776420
TI  - Urinary N-acetyl-beta-glucosaminidase in the prediction of preeclampsia.
AB  - The urinary excretion of N-acetyl-beta-glucosaminidase (NAG), a lysosomal enzyme
      of the renal tubular cells was analyzed in 177 women divided into nonpregnant
      healthy controls (n = 46), normal pregnant women in their third trimester (n =
      49), pregnant women with transient hypertension (n = 43), and women with
      preeclampsia (n = 39). Urinary activity of NAG was increased in normal pregnant
      women and in patients with transient hypertension in pregnancy compared to
      nonpregnant healthy controls. In preeclamptic women, this increase was found to
      be much higher than that corresponding to their gestational age; this fact is due
      to the tissue ischemia that precedes glomerular endotheliosis, but also tubular
      lesions caused by arteriolar vasoconstriction may have an important role.

PMID- 9776421
TI  - Pharmacokinetics of deflazacort in renal transplanted and hemodialyzed children.
AB  - Deflazacort (DFZ) pharmacokinetics was evaluated in fifteen pediatric patients on
      chronic hemodialysis or after renal transplantation, and in three normal
      children. After overnight fasting, oral DFZ 0.26+/-0.01 mg/kg (mean +/- SEM) was
      given. Serial blood samples were collected for 360 min and analyzed by HPLC for
      21-hydroxy-DFZ (21-HO-DFZ). Serum concentration profiles and pharmacokinetic
      parameters were similar in patients on hemodialysis, renal transplant recipients
      and normal children. Elimination half-life was longer in the 9 cyclosporine
      treated subjects (108.0+/-13.6 min) than in the other nine (71.2+/-8.3 min; p
      <0.02). Our finding suggests that, from a pharmacokinetic point of view, DFZ dose
      adjustment for renal function is not necessary in children with chronic renal
      failure or after renal transplantation.

PMID- 9776422
TI  - Alkalinization and hemodialysis in severe salicylate poisoning: comparison of
      elimination techniques in the same patient.
AB  - We report the case of a man who took two overdoses of aspirin, on each occasion
      suffering a grand mal fit with blood levels of salicylate of over 5 mmol/l. The
      first event was treated with hemodialysis but without effective alkalinization,
      and the second with alkalinization but without hemodialysis. The rate of decline
      in salicylate concentration was faster with alkalinization in the first 4 hours.
      Similar salicylate levels were achieved with both techniques by 24 hours post
      overdose. If a case of salicylate poisoning is to be treated with hemodialysis,
      treatment with alkalinization should still be given without delay, in order to
      prevent acidemia and to promote elimination of as much salicylate as possible via
      the kidneys.

PMID- 9776423
TI  - A case of late onset primary hyperoxaluria type I (PH-I) presented with black
      liver.
AB  - A 63-year-old woman who had received hemodialysis therapy since she fell acute on
      chronic renal failure 4 years ago presented with multiple joint pain.
      Nephrocalcinosis was not detected by abdominal X-ray when hemodialysis therapy
      was initiated. Laboratory testing showed azotemia, anemia, hypoproteinemia and
      mild liver dysfunction but no liver cirrhosis. Biopsied bone tissue demonstrated
      numerous calcium oxalate crystal depositions. Laparoscopy revealed black liver in
      macroscopic view. Histological studies showed numerous lipofuscin-like dark brown
      granules were deposited in hepatocytes. The activity of alanine : glyoxylate
      aminotransferase (AGT) was less than 0.1 U/g in biopsied patient's liver tissue.
      Generally, clinical symptoms demonstrated by Japanese primary hyperoxaluria type
      I (PH-I) patients are milder than those of European patients. Some PH-I patients
      may successfully avoid urinary tract calcification unless they fall into oliguria
      by some other causes. The lipofuscin granules are most likely the source of the
      dark color. Massive deposition of the lipofuscin granules indicated that the
      duration of the liver metabolic abnormality had lasted for long time. Thus, black
      liver may be related to a mild form of PH-I.

PMID- 9776424
TI  - Hyperkalemic renal tubular acidosis induced by trimethoprim/sulfamethoxazole in
      an AIDS patient.
AB  - A patient with the acquired immunodeficiency syndrome (AIDS) and sickle cell
      anemia presented to the University of Wisconsin Hospital on two separate
      occasions with pneumocystis carinii pneumonia (PCP). On both occasions he was
      treated with high-dose intravenous trimethoprim/sulfamethoxazole (TMP/SMX).
      Several days into each treatment course he developed hyperkalemia and systemic
      acidosis consistent with hyperkalemic renal tubular acidosis (RTA). The
      abnormalities resolved in the first instance with the addition of amphotericin B
      while continuing TMP/SMX, and in the second upon discontinuation of the TMP/SMX.
      While an increasing number of cases with TMP/SMX-induced hyperkalemia have been
      reported, hyperkalemic RTA is an uncommon complication of TMP/SMX therapy,
      occurring in patients with predisposing factors for acidosis such as aldosterone
      defects, medullary dysfunction and renal insufficiency.

PMID- 9776426
TI  - Aphtous ulcers of the mouth associated with losartan.

PMID- 9776425
TI  - Indinavir nephropathy in an AIDS patient with renal insufficiency and pyuria.
AB  - Indinavir has been described to cause crystalluria and nephrolithiasis in a
      variable number of treated patients. Acute renal failure, often reversible with
      discontinuation of the medication, induction of a diuresis and correction of
      urinary obstruction if present, occurs in a smaller percent of patients. One
      recent report described renal biopsy findings, indinavir crystals within cellular
      casts in the collecting tubules, in a patient receiving this antiretroviral
      agent. We report a second case of a patient with mild renal insufficiency and
      pyuria following indinavir therapy and describe similar renal biopsy findings.

PMID- 9776427
TI  - Nephrotic syndrome following initiation of methotrexate therapy for rheumatoid
      arthritis.

PMID- 9776428
TI  - Effect of H2-blockers on serum calcium and phosphorus in hemodialysis patients on
      calcium carbonate therapy.

PMID- 9776429
TI  - Seminal vesicle cysts in the patients with adult polycystic kidney disease.

PMID- 9776430
TI  - Renal involvement in essential monoclonal (type 1) IgG cryoglobulinemia.

PMID- 9776431
TI  - Does cisplatin stimulate erythropoietin secretion from the peritubular cells of
      the kidney?

PMID- 9776432
TI  - Rhabdomyolysis and acute renal failure due to status epilepticus.

PMID- 9776433
TI  - Codeine in post-operative pain. Study of the influence of sparteine phenotype and
      serum concentrations of morphine and morphine-6-glucuronide.
AB  - OBJECTIVE: Within the past decade, human experimental pain studies have supported
      the 50-year-old hypothesis that codeine is a prodrug, which has to be converted
      to morphine to exert an analgesic effect. This study aimed at evaluating the
      impact of sparteine phenotype and serum concentrations of morphine on the
      efficacy of codeine in post-operative pain. METHODS: Eighty-one patients with a
      pain rating of 3 or more on a 0-10 numerical rating scale 0.5 h after surgery
      were included in the study. The patients were given an oral dose of 100 mg
      codeine and rated pain with the numerical rating scale 0.5 h and 1 h after
      medication. Blood for determination of serum concentration of codeine and its
      metabolites was collected 1 h after medication, and a 12-h urine sample after
      administration of 100 mg sparteine was used to determine the sparteine phenotype.
      RESULTS: Eight patients were poor metabolizers and 66 were extensive metabolizers
      of sparteine, while the urine samples for the remaining seven patients were lost.
      In 22 patients, including the eight poor metabolizers, the serum concentrations
      of both morphine and morphine-6-glucuronide (M6G) were below the limit of
      determination of the assay, i.e. 1.5 nmol x l(-1) and 2 nmol x l(-1),
      respectively. A sum of the concentration of these two substances below 10 nmol x
      l(-1) was found in an additional eight patients. The sum of differences between
      pre- and post-operative pain ratings did not differ between the two phenotypes (P
      = 0.60), whereas the 30 patients with serum concentrations of morphine plus M6G
      below 10 nmol x l(-1) had a marginally significant lower sum than the 51 patients
      with higher levels of these substances (median 1.5 vs 2.5, P = 0.058).
      CONCLUSION: A low serum concentration of morphine and M6G seems to be common in
      patients treated with codeine for post-operative pain, and low concentrations of
      these active substances may be related to decreased efficacy of codeine.

PMID- 9776434
TI  - Comparison of ketorolac and diclofenac in the treatment of renal colic.
AB  - OBJECTIVE: To compare the efficacy and adverse effects of ketorolac and
      diclofenac in the treatment of renal colic. METHODS: In a double-blind,
      randomized clinical trial, 57 patients admitted to the emergency room for renal
      colic, received either 30 mg of ketorolac or 75 mg of diclofenac i.m.
      (intramuscularly). Evaluations were performed at 1, 2 h and 6 h after treatment.
      Pain was assessed by a four-point verbal rating scale (VRS) and a visual analogue
      scale (VAS). Only patients with at least moderate pain according to the VRS were
      included. Seventy-five milligrams of pethidine i.m. was given as rescue medicine,
      if insufficient analgesia was achieved. The adverse effects recorded were
      sedation, nausea and vomiting. RESULTS: There was no significant difference
      between ketorolac and diclofenac, with respect to pain level over time, the
      number of patients requiring rescue medicine, or the level of adverse effects.
      CONCLUSION: Ketorolac and diclofenac are equally effective in the treatment of
      renal colic.

PMID- 9776435
TI  - The effect of pre-induction clonidine on platelet aggregation during minor
      surgery.
AB  - OBJECTIVE: This paper reports the results of a prospective randomized double
      blind trial on the effects of pre-operative clonidine on platelet aggregation.
      METHODS: Thirty adult (ASA I-II) patients undergoing elective minor orthopaedic
      surgery were randomly allocated into three groups of ten patients each. In group
      I clonidine 2 microg x kg(-1), in group II clonidine 4 microg x kg(-1) and in
      group III saline placebo was administered intravenously before the induction of
      anaesthesia. Anaesthesia was induced with propofol and vecuronium and maintained
      with halothane-nitrous oxide. Platelet counts and aggregation tests were
      performed before (t0) and 1 h (t1) and 24 h (t24) after administration of the
      study drug. RESULTS: Changes in platelet counts among the groups and values over
      time were not significant. Both maximum rate and intensity of collagen-induced
      aggregation in both clonidine groups and maximum intensity of adenosine 5'
      diphosphate (ADP)-induced aggregation in the high-dose clonidine group increased
      significantly at t1. However, all these increases in aggregation were within the
      normal ranges. CONCLUSION: The effects of both low and high doses of clonidine on
      platelet aggregation appeared to be minor, and we did not observe any increases
      above the normal ranges.

PMID- 9776436
TI  - Pharmacokinetics and effects of formoterol fumarate in healthy human subjects
      after oral dosing.
AB  - OBJECTIVE: To evaluate the effects of formoterol after oral administration on
      plasma eosinophils and plasma potassium in healthy subjects. METHODS: Plasma
      concentrations of formoterol, peripheral eosinophil count and plasma potassium
      were determined during 7 h after oral administration of 168 microg of formoterol
      to eight healthy subjects. Descriptions of the concentration-time course of
      formoterol are given using a one-compartment pharmacokinetic model with first
      order absorption in four subjects and a two-compartment model in the other four
      subjects. Effects on potassium and eosinophils are described using
      pharmacokinetic/pharmacodynamic (PK/PD) modelling with the 'effect-compartment'
      approach. RESULTS: The values of the kinetic parameters were: Ka: 6.9 (h(-1)),
      t1/2, 8.5 (h), AUC: 741 (pg x h(-1) x l(-1), V(area/f): 1470 (l). Formoterol
      concentrations were related to dynamic data using a sigmoid Emax model.
      CONCLUSION: Plasma concentrations of formoterol can be measured in plasma of
      healthy subjects after oral administration. These data can be used for describing
      concentration-effect relations with respect to plasma potassium and eosinophils.
      With comparable EC50 values for the two effects, remarkable differences were
      found for k(e0) and n values.

PMID- 9776437
TI  - Influence of the cytochrome P4502D6*4 allele on the pharmacokinetics of
      controlled-release metoprolol.
AB  - AIM: The aim of the present paper was to compare the pharmacokinetics of
      metoprolol in homozygous Caucasian volunteers for the wild-type CYP2D6 allele
      (CYP2D6*1/CYP2D6*1) and heterozygous (CYP2D6*1/CYP2D6*4) Caucasians. METHODS:
      Thirty-six unrelated healthy male Caucasians were screened for two of the most
      frequently occurring mutant alleles (CYP2D6*3 and CYP2D6*4) using polymerase
      chain reaction (PCR). Twenty-four volunteers with a genotype suggesting a rapid
      hydroxylator phenotype were enrolled in a bioequivalence trial and each received
      in a randomized, cross-over fashion one of the three formulations compared. Each
      formulation contained 200 mg metoprolol tartrate/(tablet). In each of the three
      periods of the trial, one of the formulations was administered under fasting
      conditions in the morning on 4 consecutive days. Blood for quantification of
      metoprolol was drawn immediately before the last dose and in selected time
      intervals thereafter. A sensitive and specific high-performance liquid
      chromatography (HPLC) method with fluorescence detection was applied for the
      quantification of metoprolol. Pharmacokinetic parameters were determined for each
      subject and statistically compared in two groups of 16 homozygous
      (CYP2D6*1/CYP2D6*1) and six heterozygous (CYP2D6*1/CYP2D6*4) volunteers. RESULTS:
      Significant differences between homozygous and heterozygous individuals were
      observed for all pharmacokinetic parameters. The AUC in the course of one those
      interval of 24 h (AUCtau), minium steady-state concentration (C(min)ss) and
      average steady-state concentration (C(av)ss) values for heterozygous individuals
      were more than twice those of individuals. Significantly higher values for
      C(max)ss, t1/2, half-value duration (HVD) and mean residence time (MRT) were also
      observed in heterozygous volunteers. The higher concentrations of metoprolol in
      heterozygous individuals also had pharmacodynamic consequences, namely, greater
      heart rate and blood pressure reduction.

PMID- 9776438
TI  - Determination of the relative bioavailability of nedocromil sodium to the lung
      following inhalation using urinary excretion.
AB  - OBJECTIVE: To determine the relative lung deposition of nedocromil sodium
      following inhalation by comparing the amounts of nedocromil sodium excreted in
      the urine after oral and inhaled dosing. METHODS: Ten healthy volunteers
      swallowed 8 mg of nedocromil and inhaled 4 x 2-mg doses on separate days. Urine
      was collected at 0.0, 0.5. 1.0, 2.0, 5.0, 24 h and 36 h after dosing. Urinary
      excretion of nedocromil was determined by high-performance liquid chromatography.
      RESULTS: A significantly greater amount of nedocromil was excreted following
      inhalation than after oral dosing. The mean with (SD) amount excreted at 0.5, 1.0
      h and 24 h following inhalation of 4 x 2-mg doses was 41.0 (19.5), 93.0 (39.1)
      and 319.9 (138.1) microg. Corresponding values after oral administration of 8 mg
      of nedocromil were 2.1 (2.2), 6.3 (4.7) microg and 74.4 (58.8) microg,
      respectively. CONCLUSION: Nedocromil excreted in the urine at 0.5 h and 1.0 h
      after dosing is representative of the amount of drug delivered to the lungs. This
      method could be used to compare the relative bioavailability to the lungs
      following inhalation, and hence the performance of different inhaled products and
      inhalation techniques. The amount of nedocromil excreted in 24 h post-dose is
      representative of the emitted dose which was delivered to the body.

PMID- 9776439
TI  - CYP2D6 and CYP2C19 genotypes in an elderly Swedish population.
AB  - OBJECTIVE: Eighty-three healthy elderly Swedish subjects (age 87 +/- 4 years,
      mean +/- SD, range 80-98 years) were genotyped with respect to the two genetic
      polymorphisms of oxidative drug metabolism, CYP2D6 and CYP2C19, using allele
      specific polymerase chain reaction (PCR). A control population consisted of 248
      younger unrelated healthy volunteers (age 31 +/- 9 years, range 19-63 years) for
      CYP2D6, and 162 (age 30 +/- 8 years, range 19-55 years) for CYP2C19. RESULTS: No
      significant differences were found between the control groups and the elderly
      subjects with respect to the frequencies of the defect alleles CYP2D6*3,
      CYP2D6*4, CYP2C19*2 and CYP2C19*3. Neither were there any differences in the
      genotype frequencies, or the predicted phenotype frequencies. The study indicates
      that the CYP2D6 and CYP2C19 genotypes play no major role in the probability of
      reaching high age. CONCLUSION: No genetically determined differences in the
      pharmacokinetics of drugs metabolized by these two polymorphic enzymes are to be
      expected in the oldest age groups compared with younger adults.

PMID- 9776441
TI  - On-line home monitoring of drug compliance: is it feasible?

PMID- 9776440
TI  - Under-reporting of adverse drug reactions. Estimate based on a spontaneous
      reporting scheme and a sentinel system.
AB  - OBJECTIVE: Spontaneous reporting is the most common method used in
      pharmacovigilance and the best one to generate signals on new or rare adverse
      drug reactions (ADRs). Under-reporting is a major drawback of this system. The
      objective of this study was to quantify the extent of under-reporting in general
      practice and to assess the factors which influence it. METHODS: Details of ADRs
      collected through a short intensive survey were compared with primary care
      spontaneous reports received by the Castilla y Leon Regional Pharmacovigilance
      Centre during a 12-month reference period. The survey was undertaken by a random
      sample of 146 general practitioners (GPs), providing care to 149,487 people. The
      pharmacovigilance centre received reports concerning the whole regional
      population (2.5 million) covered by primary health care. The under-reporting
      coefficient (U) was estimated as the ratio between the number of effects observed
      by physicians in the survey and those spontaneously reported to the
      pharmacovigilance centre. RESULTS: The overall under-reporting rate was 1144 [95%
      confidence interval (CI): 928-1409]. Under-reporting was greater for psychiatric
      (2119; 945-4752) and gastrointestinal (1946; 1424-2659) disorders. Severe effects
      were more reported (U = 605; 151-2431) than moderate (863; 473-1575) and mild
      (1209; 973-1503) ones. The under-reporting rate was lower for drugs recently
      marketed (706; 406-1230) and slightly lower for unlabelled effects (1031; 641
      1657). CONCLUSION: The under-reporting rate of ADRs is considerable, though not
      homogeneous for the different cases. This should be taken into account when
      comparing adverse effects (AEs) for different drugs. Under-reporting seems to be
      positively selective, as it involves mainly the less severe and better-known
      effects, preserving the value of spontaneous reporting for signal detection.

PMID- 9776442
TI  - Hydroxyurea influences adrenocortical function in humans.

PMID- 9776443
TI  - Mediators in polytrauma--pathophysiological significance and clinical relevance.
AB  - Multiple trauma induces an inflammatory response syndrome of the whole body that
      is triggered by (a) hemorrhage inducing an ischemia/reperfusion (I/R) syndrome
      and (b) fractures or organ contusions inducing tissue-repair processes. I/R
      injury generates oxyradical/proteolytic metabolites and adhesion molecules, while
      tissue and endothelial injury directly stimulate complement, coagulation and
      kinin pathways. Membrane-derived phospholipase A2 and lipid mediators potentiate
      cellular interactions and increase microvascular permeability. The tissue-repair
      process mediates macrophage/monocyte and T-cell activation which releases pro-
      and anti-inflammatory cytokines. Mediator action follows a "three-level model",
      proposing that depending on the degree of traumatic injury cellular and humoral
      responses may spread from a cellular to an organ and then a systemic level. The
      systemic response can result in a severe immunological dys-homeostasis that
      potentially hazards the survival of the trauma patient by uncontrollable cellular
      dysfunction, appearing clinically as multiple organ-dysfunction syndrome. Blood
      mediator concentrations often parallel the inflammatory process; initially, high
      levels of cytokines are followed by severe organ dysfunction. However,
      interpretation of these data remains difficult due to distinct beneficial or
      detrimental effects of mediators on the different levels of inflammation and
      missing prognostic threshold values, indicating a risk of adverse effects. Future
      studies must determine pro- and anti-inflammatory mediators directly, during the
      intensive care therapy, and evaluate their clinical relevance prospectively for
      the different levels of inflammation at local and systemic sites.

PMID- 9776444
TI  - Scores in polytrauma--do they help?
AB  - BACKGROUND: The answer to the question "Scores in polytrauma - do they help ?" is
      discussed. DISCUSSION: One of the two sections deals with the role of scores used
      for clinical decision making in individual patients and, in the other, the
      significance of scores in improving patient care is analyzed. RESULTS: It is
      shown that scores may be helpful in both regards. However, certain methodological
      limitations of scores have to be considered.

PMID- 9776445
TI  - Clinical and pathophysiological significance of severe neurotrauma in
      polytraumatized patients.
AB  - INTRODUCTION: Traumatic brain injury (TBI) is present in up to two-thirds of
      multiply injured patients. The degree of TBI influenced the mortality and
      morbidity of multiple trauma significantly. RESULTS: Important prognostic
      predictors are: injury severity score (ISS); Glasgow coma score [(GCS), motor
      score]; pupil size and reactivity; coma grade and duration; age; morphological
      primary brain lesion; and pathophysiological changes leading to secondary brain
      damage. The time course of brain edema, raised intracranial pressure and,
      especially, pathophysiology of disturbed cerebral blood flow and metabolism
      characterizes early and late periods of ischemic vulnerability. CONCLUSION: These
      should be taken into consideration when planning operative procedures in multiple
      trauma patients. Avoidance of secondary ischemic brain damage by reducing the
      number of systemic insults (hypovolemia, hypotension, hypoxia) will improve
      prognosis of critically ill polytraumatized patients with head injury.

PMID- 9776446
TI  - Management priorities in patients with polytrauma.
AB  - BACKGROUND: The basic principles for the treatment of the polytraumatized patient
      is early resuscitation, followed by a physical examination and diagnostic
      studies. These are performed to establish the priorities for life-saving
      management and further treatment. DISCUSSION: Trauma management regarding
      musculoskeletal injuries is discussed in four different distinguished periods:
      (1) acute or resuscitation period (0-3 h); (2) primary or stabilization period (3
      72 h); (3) secondary or regeneration period (days 3-8); and (4) tertiary or
      rehabilitation period (beyond day 8). For management during the acute period, a
      trauma algorithm is described, which consists of four different steps: (1) first
      look; (2) shock treatment; (3) check up; and (4) control and diagnosis. During
      the acute period, decompression of organ cavities (tension pneumothorax, cardiac
      tamponade) is performed along with life-saving operations for hemorrhage control
      of thoracic, abdominal, pelvic or external bleeding. The primary period (3-72 h)
      of treatment starts when the vital functions have been stabilized. During this
      period, so-called 'day-one' surgery is performed. During the secondary period
      (days 3-8), a phase of regeneration, a secondary deterioration of organ function
      must be prevented. During the tertiary phase (beyond day 8), in most cases,
      recovery usually continues and final reconstructive operations can be performed.

PMID- 9776447
TI  - Outcome after polytrauma.
AB  - BACKGROUND AND AIMS: Outcome refers to the different facets of consequences
      resulting from an event or intervention. These consequences may be relevant for
      an individual patient, but also for society. There is a growing recognition that
      clinical research needs to define and focus on the outcomes of medical care.
      Outcome research should help health care professionals to better evaluate the
      effectiveness of specific interventions or a therapeutic concept. This broader
      base of evidence should then benefit the patients. METHODS: The literature was
      reviewed with respect to concepts of outcome research as well as results of
      outcome research after major trauma. RESULTS: Measuring outcome might be relevant
      for research purposes as well as in daily surgical practice. In the past,
      clinical research in trauma care has tended to focus on survival. Mortality rates
      are not out, complication rates are not out, but their value is limited and
      restricted to given scenarios with high mortality rates. New outcomes have to be
      added: such a functional status, emotional health, social interaction, cognitive
      function, degree of disability and other indicators of health. CONCLUSION:
      Despite differences in injury pattern and severity of injury, there is strong
      evidence from the literature that the quality of life is significantly impaired
      after major trauma. This is true for functional outcome as well as for psycho
      social outcome in up to 70% of patients.

PMID- 9776448
TI  - Differentiated thyroid cancer in children and adolescents.
AB  - INTRODUCTION: There have been only a few studies on differentiated childhood
      thyroid cancer (DTC) in children and adolescents. METHODS: We analyzed the
      characteristics of DTC with respect to age, gender and histology in 114 patients
      under 18 years of age. In a questionnaire-based survey, data of 114 patients,
      aged between 3 years and 18 years, was collected from 65 clinical institutions in
      Germany. Characteristics of 80 females and 34 males were evaluated, and the
      prognostic effect of age, gender, histology, multicentric growth, tumor stage and
      N-status on distant metastases was tested using multivariate discriminant
      analysis. Between-group comparison was performed using student t-test and chi
      squared test. RESULTS: The incidence of DTC in females was higher than in males
      with a peak of female:male ratio at puberty, which was more pronounced in
      children with papillary thyroid cancer, but not with follicular thyroid cancer.
      Papillary thyroid cancer was associated with more advanced disease (P=0.009),
      more lymph-node involvement (P=0.007) and more distant metastases (P=0.02)
      compared with follicular thyroid cancer. Multivariate analysis showed advanced
      tumor stage as the only significant factor (P=0.02) associating with distant
      metastasis. CONCLUSION: It can be concluded that in children and adolescents: 1.
      The incidence of papillary thyroid cancer is higher in females than males, with a
      peak at puberty. 2. The only significant factor associated with distant
      metastases is the advanced tumor stage. 3. Childhood thyroid cancer is frequently
      associated with lymph-node involvement, distant metastases and advanced tumor
      stage. 4. Papillary childhood thyroid cancer is more aggressive than follicular
      type.

PMID- 9776449
TI  - Surgical training and vocal-cord paralysis in benign thyroid disease.
AB  - INTRODUCTION: Operations performed by a trainee surgeon should not result in a
      higher risk of complications. However, there is little information about
      identifying risk factors for primary surgery of benign, non-autoimmune goiter.
      METHODS: This study correlates experience of the surgeon and other potential risk
      factors with palsy rates of the recurrent laryngeal nerve over an 18-month
      period. Radical removal of all nodular thyroid tissue and principal nerve
      identification were standard procedures. RESULTS: Of a total of 405 operations
      per side, 55.8% were subtotal resections, 11.8% extended subtotal (near total)
      resections and 33.1% lobectomies. The overall initial and permanent palsy rates
      of "nerves at risk" were 8.9% and 1.2%, respectively. Patients' age, gender and
      weight, as well as endocrine activity of the thyroid gland were not associated
      with increased complications. CONCLUSION: The risk of nerve damage increased
      significantly and independently with size of goiter and extent of resection, but
      did not correlate with the surgical experience. In conclusion, the training of
      surgeons is safe if cases are carefully selected and the surgeons in training are
      supervised.

PMID- 9776450
TI  - Preoperative diagnostics in pancreatic carcinoma: would less be better?
AB  - OBJECTIVE: The objective of this study was to investigate the value of
      preoperative diagnostics in patients with pancreatic carcinoma in terms of tumor
      diagnosis and evaluation of resectability. PATIENTS/METHODS: From 1 September
      1985 to 31 December 1997, 408 patients shown by histology to have a ductal
      (n=330) or periampullary carcinoma (n=78) were treated at our hospital. RESULTS:
      In determining the presence of tumor, ultrasonography and computed tomography
      (CT) had a sensitivity of 88.3% and 94.0%, respectively; combined, they had a
      sensitivity of 96.2%. Endoscopic retrograde cholangiopancreatography (ERCP) had a
      sensitivity of 96.2%. Preoperative aspiration biopsy cytology had a sensitivity
      of 71.4%. No correlation was found in the patients undergoing surgery between the
      preoperative level of serum CA 19-9 and the presence of distant metastases. Tumor
      infiltration of the portal vein was shown with a sensitivity of 33.3%, 24.3%, and
      76.5% and a specificity of 93.9%, 98.9%, and 65.6% by ultrasonography, CT, and
      angiography, respectively. Ultrasonography and CT detected liver metastases or
      peritoneal carcinomatosis with a sensitivity of 35.9% each and a specificity of
      91.9% and 91.7%, respectively. CONCLUSION: This study shows that, in 96% of
      patients with pancreatic carcinoma, ultrasonography and CT are adequate for
      diagnosis and for the evaluation of resectability. ERCP is not the method of
      choice in the diagnosis of pancreatic carcinoma due to its invasiveness and to
      the fact that it fails to demonstrate the pathological anatomical location of the
      tumor; it should only be used if a tumor is suspected despite negative results on
      ultrasonography and CT or as an additional diagnostic method to differentiate
      between chronic pancreatitis and carcinoma. On account of the low sensitivity of
      percutaneous aspiration biopsy cytology, this method is not necessary
      preoperatively and may even lead to the spread of tumor cells. In 7% of patients,
      routine laparoscopy would additionally show liver metastases or peritoneal
      carcinomatosis not demonstrated using the imaging techniques.

PMID- 9776451
TI  - Laceration of a benign adrenal adenoma mimicking a splenic rupture.
AB  - Lacerations of adrenal tumors are very rare events and have been described for
      myelolipoma, pheochromocytoma, and cortisol-producing adenoma. We report on a
      patient who was admitted with suspected splenic rupture. Computed tomography
      showed a mass 14 cm in diameter adjacent to the spleen, but selective angiography
      revealed blood supply by the left suprarenal artery. A ruptured adrenal tumor was
      therefore diagnosed and resected. No hormone production was detected.
      Histologically a benign adrenal adenoma was found. Frequency, diagnosis and
      therapy of adrenal masses are discussed.

PMID- 9776452
TI  - Severe head injury combined with orthopedic and vascular trauma of the limbs.
AB  - From 1982 to 1992, 2766 brain injury patients were admitted to the University
      Hospital San Cecilio of Granada, Spain. In 873 cases head injury was concomitant
      with other injuries but the association of severe head injury and combined
      orthopedic and vascular trauma of the limbs was observed only in 23 cases
      (incidence 2%). Thirteen patients were scheduled for revascularization, and of
      these secondary amputation was mandatory in two cases to keep rising intracranial
      pressure under control. Except for epidural hematomas which constitute an
      absolute neurosurgical emergency, combined orthopedic and vascular trauma of the
      limbs can be treated before head injury. However, we prefer to work with two
      operating teams simultaneously. Physical examination and judicious arteriography
      provide means for prompt diagnosis and treatment of the injured limb. The
      compartment syndrome should be anticipated and fasciotomy should be used
      routinely. Vascular repairs normally using reverse autogenous vein are the first
      priority, but we must always bear in mind the deleterious effects of the
      revascularization syndrome which expose the brain to a second aggression, and
      amputation, when necessary, should be undertaken to reduce mortality.

PMID- 9776453
TI  - Results of bypasses to the anterior tibial artery through the interosseous
      membrane.
AB  - The purpose of the present study was to retrospectively evaluate the results of
      anatomically tunneled grafts to the anterior tibial artery for distal
      revascularization in terms of patency and limb salvage rates as well as local
      morbidity, which can lengthen the postoperative hospital stay. Twenty-three
      patients received 24 bypasses to the anterior tibial artery, with grafts tunneled
      through the interosseous membrane. The mean age was 67 years; 10 patients were
      diabetic, 12 were smokers, 9 presented with significant coronary artery disease,
      and 2 with chronic renal insufficiency. The donor vessel was the common femoral
      artery in 17 cases, the superficial femoral artery in 4, and the infra-articular
      popliteal artery in 3. The graft material consisted in the reversed saphenous
      vein in 4 cases, the non-reversed devalvulated ex situ saphenous vein in 11,
      composite polytetrafluoroethylene (PTFE) + inversed saphenous vein in 6, and PTFE
      alone in 3 cases. No postoperative mortality was observed, nor was there
      postoperative graft occlusion or need for major amputation. The average
      postoperative length of stay in the hospital was 9.7 days. Two local surgical
      wound complications were observed, which did not necessitate a postoperative
      hospital stay exceeding 15 days. Cumulative primary patency and limb salvage
      rates at 3 years were 50% and 70%, respectively. Anatomic tunneling of grafts to
      the anterior tibial artery yields patency and limb salvage rates comparable to
      those reported in the literature for distal bypasses and, considered overall, an
      acceptably low local morbidity and short hospital stay. Definitive superiority
      over externally tunneled grafts, however, is not definitely demonstrated by this
      study and should be prospectively tested.

PMID- 9776454
TI  - Haematogenous tuberculous infection following revision of a loosened total hip
      replacement.
AB  - A case of tuberculous arthritis complicating revision of a total hip replacement
      (THR) is reported. Primary THR was performed for arthrosis of the hip and the
      patient underwent revision because of aseptic loosening. After this surgical
      procedure, secondary infection with Mycobacterium tuberculosis occurred.
      Bacterial contamination due to haematogenous spread probably from a reactivated
      old quiescent tuberculous pleural focus is proposed as the most likely source of
      infection in this patient. Tuberculous infections in THR are rare but
      prophylactic use of antituberculous drugs in patients with a history of
      tuberculosis may reduce the risk of reactivation of old foci and serve to
      eliminate contamination of prosthetic replacements.

PMID- 9776455
TI  - Growth inhibition of pancreatic tumor cells by modified antisense
      oligodeoxynucleotides.
AB  - INTRODUCTION: Pancreatic adenocarcinomas are largely resistant to apoptosis. More
      than 50% of pancreatic tumors reveal mutations in the p53 tumor suppressor gene.
      METHODS: We investigated the growth of pancreatic tumor cells after
      downregulation of p53 protein expression by antisense oligodeoxynucleotides.
      RESULTS: Proliferation and p53 expression of PancTu-I cells overexpressing mutant
      p53 protein were inhibited by antisense oligodeoxynucleotide treatment. When
      analyzed, two of three other pancreatic tumor cell lines with mutated p53 were
      also inhibited in their growth. Two of two wild-type (wt) p53 pancreatic tumor
      cells were not significantly influenced by p53 expression and were, only to a
      lesser extent, affected in their proliferation. K562 cells (lacking p53 mRNA) and
      normal human skin fibroblasts used as a target mismatch control showed no changes
      in proliferation rates with treatment. The different biological effects in the
      various cells were not caused by differences in the uptake of the
      oligodeoxynucleotides as monitored by confocal laser-scanning microscopy.
      CONCLUSIONS: Truncation and 5'- and 3'-lipophilic modifications of the
      oligodeoxynucleotides drastically enhanced the growth inhibition of PancTu-I
      cells, which were resistant to apoptosis-inducing agents. Furthermore, a higher
      sequence-specificity of the observed effects was achieved with these compounds.

PMID- 9776456
TI  - Photochemotherapy of experimental colonic tumours with intra-tumorally applied
      methylene blue.
AB  - INTRODUCTION: Phototoxicity of intra-tumoral injected methylene blue (MB+) was
      studied in 48 experimental colonic tumours in comparison with photosan-3, Zn
      phthalocyanine and tetrasulphanated ClAl-phthalocyanine. METHODS: In mice.
      xenotransplanted subcutaneous tumours about 1 cm in diameter were treated
      photodynamically twice, with different sensitisers. The irradiation was performed
      at the sensitiser-specific wavelength, and a density of 100 mW/cm2 and a dose of
      100 J/cm2. RESULTS: Light alone without sensitiser did not induce any effect in
      mice tumours. Surprisingly, Al-phthalocyanine could only be used for intratumoral
      injections because of toxic effects after intravenous applications in nude mice.
      Using MB+ (1%), 75% of the tumours were destroyed by a single photodynamic
      treatment (PDT). In addition, toxicity of MB+ was most intense when compared with
      Zn-phthalocyanine and photosan-3. However, after the second PDT, there was no
      statistically significant difference among these sensitisers. Dark toxicity of
      MB+ (1%) could be well demonstrated by sufficient sensitiser incorporation
      without irradiation, which led to a stationary tumour volume up to 3 weeks after
      injection. CONCLUSION: Intra-tumoral MB+ PDT is a potential treatment for
      inducing necrosis in vivo. With regard to tumour tissue, the selectivity of MB+
      is high and depends on a precise local injection of the dye.

PMID- 9776457
TI  - The use of intravital microscopy in surgical research. 26-years of experience
      analyzed by studies presented at the Surgical Forum of the Annual Congress of the
      German Society of Surgery.
AB  - Recent developments in intravital microscopy make this technique an attractive
      approach to studying microvascular, cellular, and molecular mechanisms of
      distinct surgical diseases. We investigated the value of this technique in
      surgical research laboratories by analyzing the studies presented during the past
      26 years (1972-1997) at the Surgical Forum of the Annual Congress of the German
      Society of Surgery. From a total of 2279 papers 188 contributions (8.3%)
      presented data which derived from the analysis of the microcirculation using
      techniques, such as H2 and 133Xe clearance, autoradiography, thermodiffusion,
      laser Doppler fluxmetry, laser speckle, radioactive and fluorescent microspheres,
      polarographic oximetry, and intravital microscopy. There were 72 presentations
      (3.2% of all contributions) reporting the use of intravital microscopy, thus
      reflecting 38.3% of all microcirculatory analyses. Although these numbers may be
      considered quite small, analysis over time revealed a significant (P<0.05)
      increase in the number of microcirculatory studies (11.4%) and in particular of
      those using intravital microscopy (6.3%) in the 1990s when compared to the 1970s
      (5.3%; 0.1%) and 80th (7.1 %; 1.3%). In 1997, 27 of 165 contributions (16.4%)
      included microcirculatory analyses, and 18 of the 165 contributions (10.9%)
      reported results analyzed by intravital microscopy. Thus our analysis reflects an
      increasing interest of surgical researchers to study in vivo the
      microcirculation, and by doing so to use intravital microscopy for the
      elucidation of mechanisms of surgical disease.

PMID- 9776458
TI  - Technique and results of the retroperitoneoscopic adrenalectomy via a lumbar
      approach.
AB  - INTRODUCTION: Since 1992, endoscopic techniques have been used increasingly in
      adrenal-gland surgery. In the present paper, the technique of the
      retroperitoneoscopic adrenalectomy via a lumbar approach is described. METHODS:
      The patient is placed in a lateral decubitus position. In the first step, a
      dilatation trocar is introduced in the retroperitoneal space to create an
      artificial cavity. The dilatation trocar is replaced by a blocking trocar to
      close off the operating field. After insufflation of CO2, two additional trocars
      are introduced in the area of the conventional flank incision. Adrenalectomy is
      performed via these ports. Once the adrenal gland is completely mobilized, it is
      inserted into a sterile plastic bag and removed through the 1.5-cm incision.
      CONCLUSION: The retroperitoneoscopic approach to the adrenal gland appears to be
      suitable for benign adrenal-gland tumors up to a size of 6 cm.

PMID- 9776459
TI  - Laparoscopic vs conventional appendectomy--a meta-analysis of randomised
      controlled trials.
AB  - AIM: To compare the effectiveness and safety of laparoscopic and conventional
      "open" appendectomy in the treatment of acute appendicitis. METHODS: Meta
      analysis of randomised controlled trials available by May 1998 that compared both
      techniques. Within each trial and for each outcome an effect size was calculated;
      the effect sizes were then pooled by a random-effects model. RESULTS: We
      summarised outcome data of 2877 patients included in 28 trials. Operating time
      was +16 min (95% confidence interval +12-20 min) longer for laparoscopic
      appendectomy. Overall complication rates were comparable, but wound infections
      were definitely reduced after laparoscopy [rate difference -4.2%, (-2.3% to 
      6.1%)]. Intra-abdominal abscesses, however, occurred slightly more frequently
      [+0.9%, (-0.4% to +2.3%)]. Hospital stay after laparoscopic appendectomy was 15 h
      (8-23 h) shorter, and patients returned to full fitness or work 7 days (5-9 days)
      earlier. Pain intensity on day 1 was slightly less. Heterogeneity was present for
      some outcome measures due to methodological differences among the primary
      studies. CONCLUSION: Laparoscopic appendectomy reduces wound infections and eases
      postoperative recovery. Nevertheless, the various differences among the primary
      studies and their partly flawed methodology make it difficult to generalise from
      these findings.

PMID- 9776460
TI  - The genetics of Parkinson's disease and parkinsonian syndromes.
AB  - The finding of a mutation in the alpha-synuclein gene in a rare autosomal
      dominant form of idiopathic Parkinson's disease (IPD), has prompted increased
      interest in identifying genes that account for the more common sporadic form. A
      number of association studies have suggested that functional polymorphisms in
      genes that play a role in dopamine, drug and toxin metabolism may increase the
      relative risk of IPD. Unfortunately, patient numbers are often small, and the
      results have not been consistently reproduced. This article reviews the evidence
      from epidemiological, imaging and genetic studies to determine the role of
      genetic susceptibility in IPD and parkinsonian syndromes.

PMID- 9776461
TI  - Neurological manifestations of malignant and non-malignant dysglobulinaemias.
AB  - The main neurological manifestations associated with malignant and non-malignant
      dysglobulinaemias are reviewed. These disorders are classified according to
      topographic features, pathological changes or association with specific plasma
      cell disorders. The main clinical, laboratory, immunological and pathological
      features are summarized. Knowledge of the pathogenesis in this group of disorders
      has clearly increased in recent years, allowing better diagnosis and treatment.

PMID- 9776462
TI  - Generalized tonic-clonic status epilepticus: causes, treatment, complications and
      predictors of case fatality.
AB  - We retrospectively reviewed the clinical course of 66 patients treated for
      generalized tonic-clonic status epilepticus at the Ege University neurological
      intensive care unit from 1988 to 1997. Seventy-two per cent of the study group
      had a pre-existing seizure disorder, and antiepileptic drug withdrawal was the
      most prominent cause of status epilepticus. The other causes included drug
      toxicity, central nervous system infection, cerebrovascular disease, tumour and
      trauma. Seventy-three per cent of all patients responded to the first-line
      therapy (diazepam and/or phenytoin), and the remainder were considered to have
      refractory status epilepticus and required pentobarbital anaesthesia. Overall
      case fatality was 21%, but death could be attributed directly to status
      epilepticus and/or treatment complication in 10% of the study group. Major
      determinants of fatal outcomes were: increasing age, longer duration of status
      epilepticus before initiation of therapy and central nervous system infection as
      a causal factor.

PMID- 9776463
TI  - CAG repeat length and clinical features in three Italian families with
      spinocerebellar ataxia type 2 (SCA2): early impairment of Wisconsin Card Sorting
      Test and saccade velocity.
AB  - We report on the clinical, neuropsychological, neurophysiological, computerized
      eye movement, magnetic resonance imaging (MRI) and molecular findings from 17
      individuals affected with spinocerebellar ataxia type 2 (SCA2) belonging to three
      families. The average age at onset of the symptoms was 35.6, 11.9 (mean, SD)
      years. The mean age at onset of the symptoms in the parents was 44.8, 8.2 years,
      and in the offspring it was 28.7, 7.2 years. In 12 parent-child pairs, the mean
      anticipation was -15.75, 9.1 years (range -8.1 to -23.3 years, t = -4.9, P = <
      0.002). The mutated SCA2 alleles ranged from 38 to 42 CAG repeats, while the
      normal alleles ranged from 22 to 24 repeats, with 97% of the alleles having 22
      repeats. Small differences in the number of CAG repeats influenced the age at
      onset and rate of progression of the disease considerably. Indeed, patients
      presenting with their first symptom at an age of 35 years or later with a slower
      course of the disease harboured between 38 and 39 repeats. In contrast, patients
      carrying > or = 40 CAG repeats manifested the disease prior to 30 years of age
      and had a faster disease progression toward incapacity. The presenting symptom
      was always gait ataxia. Slow saccades occured from the beginning of the disease
      despite normal delay, accuracy and smooth pursuit eye movements. The
      neuropsychological study showed early and selective impairment of conceptual
      reasoning ability, as detected by the Wisconsin Card Sorting Test (WCST). It is
      noteworthy that a significant mutual relationship was observed between
      performance on the WCST and saccade velocity. All of these findings favour the
      hypothesis that the disease process of SCA2 in regions other than the cerebellum
      and brain stem affects severely and early those cortical structures involved in
      the control of both visually guided saccades and WCST performance.

PMID- 9776465
TI  - Colour vision abnormalities do not correlate with dopaminergic nigrostriatal
      degeneration in Parkinson's disease.
AB  - Sensory disturbances such as olfactory or visual dysfunctions are common in
      Parkinson's disease (PD). A possible relationship between distorted colour
      discrimination and the nigrostriatal dopamine deficit is still a matter of
      debate. We examined 31 de novo Parkinsonian patients with [123I]beta-CIT single
      photon emission tomography (SPECT). We used a single-head gamma-camera and
      calculated the binding ratio striatum/cerebellum (specific/nonspecific binding)
      of [123I]beta-CIT uptake. On the same day, we performed the Farnsworth-Munsell
      100 Hue Test (FMT) in these patients and estimated the total error score, in
      order to investigate abnormalities of colour vision. Parkinsonian patients' total
      error score was higher compared with an age- and sex-matched control group (P = <
      0.0001), whereas disability scores of the Hoehn and Yahr scale (P = 0.019,
      Spearman r = 0.419) and the Unified Parkinson's Disease Rating Scale (P = 0.039,
      Spearman r = 0.373) correlated with total error score. No significant association
      appeared between total error score (Spearman r = -0.119, P = 0.525) and [123I]P
      CIT-SPECT ratio. Thus both total error scores of the FMT and [1231]beta-CIT-SPECT
      binding ratios have been found to reflect the severity of PD. However, only
      [123I]beta-CIT SPECT reflects degeneration of dopaminergic neurons of the basal
      ganglia, but does not reflect alterations of the visual system and/or extranigral
      lesions in PD. From our results, we speculate that FMT may be a valuable clinical
      method to measure extranigral lesions of the visual system in PD.

PMID- 9776464
TI  - Prevalence of factor V Leiden mutation in young adults with cerebral ischaemia: a
      case-control study on 225 patients.
AB  - Cerebral ischaemia in young adults is a well-recognised disease, and
      approximately half of the cases remain aetiologically unclear despite extensive
      investigations. Thrombophilias are known to cause a subset of ischaemic strokes
      in this population. The factor V Leiden (FVL) mutation, causing resistance to
      activated protein C, has recently been recognised as the most important genetic
      thrombophilia in the Western population. Carriers of this gene mutation have a
      sevenfold increased risk of phlebothrombosis. We undertook this study to evaluate
      whether the FVL mutation constitutes a risk factor for juvenile cerebral
      ischaemias. A total of 225 patients aged < or = 45 years at onset of cerebral
      ischaemia and 200 age-matched healthy controls were investigated. The overall
      frequency of heterozygosity for the FVL mutation did not differ significantly
      between patients (8.4%) and controls [6.0%; odds ratio (OR) 1.4, 95% confidence
      interval (CI) 0.7-3.1]. In the subgroup of patients with cryptogenic cerebral
      ischaemia (n = 94), however, a significantly higher frequency of this gene defect
      (15.9%) was found compared with the controls (OR 3.0, CI 1.3-6.6). Further trends
      towards higher frequencies of the FVL mutation were found in patients with patent
      foramen ovale (OR 1.9), individual (OR 2.1) or family history of previous
      thrombembolisms (OR 2.0), and in those aged 25 years at onset of disease (OR 1.9,
      all not significant). In conclusion, the FVL mutation is not a risk factor for
      cerebral ischaemia of the young. However, our results suggest that this gene
      mutation plays an aetiological role in the subgroup of patients suffering from
      'cryptogenic' ischaemic events.

PMID- 9776466
TI  - Murine typhus presenting as subacute meningoencephalitis.
AB  - Murine typhus is a febrile systemic illness, presenting with headache and
      undulating fever. Neurological involvement is considered a rare complication.
      During 1994 and 1995, 34 patients admitted to our hospital were diagnosed as
      having murine typhus. Five of these patients presented with a syndrome of
      subacute "aseptic" meningitis or meningoencephalitis. Three had bilateral
      papilloedema and 2 had focal neurological signs. None had a rash or other
      systemic findings suggestive of rickettsial disease. The diagnosis was based on
      serum and cerebrospinal fluid serology and on prompt response to doxycycline
      therapy. These cases suggest that neurological involvement in murine typhus is
      more common than previously suspected and that murine typhus should be included
      in the differential diagnosis of subacute meningitis in endemic areas.

PMID- 9776467
TI  - Clinimetrics of postural instability in Parkinson's disease.
AB  - Judgement of the ability to recover balance after a sudden shoulder pull is used
      as a clinical measure of postural instability in Parkinson's disease. To further
      evaluate its merits, we compared this 'retropulsion test' with dynamic
      posturography in 23 Parkinson patients. Dynamic posturography involved 20 serial
      'toe-up' support surface rotations, which induced backward body sway. We found a
      moderate correlation (Spearman's p = 0.54; P < 0.05) between the retropulsion
      test and body sway after platform rotations during the 'off' phase, but no
      correlation during the 'on' phase (Spearman's p = 0.43; P = 0.11). These results
      cast doubt on the use of the retropulsion test as a measure of postural
      instability in Parkinson's disease.

PMID- 9776468
TI  - Saccadic slowing in myotonic dystrophy and CTG repeat expansion.
AB  - Recent studies have shown that the severity of the several clinical symptoms of
      myotonic dystrophy (DM) is closely related to the size of a CTG triplet repeat in
      the gene encoding myotonin protein kinase. Although neurotological findings,
      including saccadic slowing in patients with DM, have been reported, the
      relationship between these neurotological findings and elongation of the CTG
      triplet repeat has not been discussed to our knowledge. We made a case-control
      study that compared the saccadic velocity in 13 patients with DM and in 13
      controls matched for age and sex. We also examined the correlation between the
      saccadic velocity in DM patients and the size of the expanded DNA fragment (EF)
      obtained by Southern blot analysis with EcoRI or BglI. We found: (1) The primary
      eye position was normal in 9 of 12 patients. Divergent strabismus was present in
      3 patients. (2) The range of ocular movement was normal in 2 patients, nearly
      normal in 5 and minimally limited in the other 5. (3) Only 1 patient had lateral
      gaze nystagmus, which was fine and transient. (4) The horizontal saccades were
      essentially normometric in 11 of the 13 patients, slightly hypometric in 1 and
      obviously hypometric in 1. These last 2 patients had the second longest and
      longest EF sizes. The vertical saccades were essentially normometric in 8 of 12
      patients, hypermetric in 3, and hypometric in the 1 with the longest EF size. (5)
      The saccadic velocity in the DM patients was significantly lower than that in the
      controls in the horizontal or vertical direction, the difference being more
      prominent in the horizontal direction. (6) The correlation coefficients between
      horizontal saccadic velocity and EF size, 0.801 (EcoRI) and 0.756 (BglI), had a
      strong negative correlation (P < 0.01 for both EcoRI and BglI). No statistically
      significant correlation was found between vertical saccadic velocity (upward and
      downward) and EF sizes. Although it was difficult to determine whether saccadic
      slowing was caused by central oculomotor system involvement or extraocular muscle
      atrophy, the absence of gaze-evoked nystagmus in almost all of the patients
      favours the latter. Our study shows that neurotological examinations that include
      a saccadic velocity test are very useful for detecting subtle eye movement
      abnormalities in DM and for quantitatively evaluating the clinical severity of
      DM.

PMID- 9776469
TI  - Metabolic changes in patients with mitochondrial myopathies and effects of
      coenzyme Q10 therapy.
AB  - We used a standardized bicycle ergometry protocol with a stepwise increasing
      workload (30-100 W) to evaluate various metabolic factors for the diagnosis and
      metabolic monitoring of mitochondrial encephalomyopathies. All patients (n = 9)
      showed pathological venous lactate/pyruvate (L/P) ratios, which normalized in
      three patients after 6 months of coenzyme Q10 (CoQ) therapy. Thus, the L/P ratio
      proved to be the clinically most useful parameter in the evaluation and
      monitoring of mitochondrial diseases, showing higher sensitivity than lactate
      measurements only. CoQ may exert a favourable effect in some patients with
      mitochondrial diseases.

PMID- 9776470
TI  - Correlation between cognitive status and cerebral inositol in Alzheimer-type
      dementia.

PMID- 9776471
TI  - Rhino-orbito-cerebral mucormycosis.

PMID- 9776472
TI  - Anti-Ri positive opsoclonus-myoclonus-ataxia in ovarian duct cancer.

PMID- 9776473
TI  - Effects of a novel purine nucleoside phosphorylase inhibitor, BCX-34, on
      activation and proliferation of normal human lymphoid cells.
AB  - The antiproliferative effect of BCX-34 was tested in normal human peripheral
      blood mononuclear cells (PBMCs) induced to proliferate with OKT3, tetanus toxoid,
      the mixed lymphocyte reaction, or IL-2. In the case of OKT3, tetanus toxoid, or
      the MLR the IC50s ranged between 0.7 and 4 microM. With IL-2, the IC50 was 14.6
      microM. In T-cells purified by rosetting the IC50 with IL-2 was 0.62 microM. In
      CD4 or CD8 cells obtained by magnetic activated cell sorting the IC50s with IL-2
      were 0.24 and 0.62 microM, respectively. BCX-34 inhibition of proliferation in
      human PBMCs may not depend entirely upon the accumulation of intracellular dGTP
      because tetanus toxoid-induced proliferation was inhibited in the absence of
      deoxyguanosine and was not reversed by deoxycytidine. BCX-34 did not inhibit IL-2
      release from PBMCs and did not alter PBMC viability. The results of these studies
      show that BCX-34 is a potent inhibitor of normal human T-cell proliferation
      induced by antigenic or IL-2 stimulation. BCX-34 in normal human T-cells has a
      deoxyguanosine-independent mechanism to suppress in vitro proliferation. BCX-34
      appears to have little effect on T-cell viability. The data suggest that BCX-34
      may be useful in the treatment of T-cell proliferative disorders.

PMID- 9776474
TI  - Differential regulation by thalidomide and dexamethasone of cytokine expression
      in human peripheral blood mononuclear cells.
AB  - Immunosuppressive drugs are used routinely to reduce the inappropriate production
      of cytokines in an immune response. Recent attention has focused on drugs that
      selectively inhibit specific cytokines. Both thalidomide and dexamethasone have
      been reported to exhibit immunomodulatory effects on cytokines in vitro. We
      wished to examine the effects of thalidomide and dexamethasone on the production
      of cytokines by peripheral blood mononuclear cells (PBMC), following mitogenic
      stimulation, at the level of both secreted product and mRNA production. PBMC from
      healthy human volunteers were stimulated optimally with phytohaemagglutinin (PHA)
      in the presence of varying concentrations of thalidomide and dexamethasone using
      dimethyl sulphoxide (DMSO) as the solvent. Analysis of supernatants by enzyme
      linked immunosorbent assay (ELISA) showed that thalidomide caused a dose
      dependent inhibition of the pro-inflammatory cytokines interleukin 6 (IL-6) and
      tumour necrosis factor alpha (TNF-alpha), maximally reducing production by 20 (P
      < 0.05) and 30% (P < 0.01), respectively, compared with controls. However,
      thalidomide did not affect either proliferation or the production of interleukin
      2 (IL-2), interleukin 4 (IL-4) or interleukin 10 (IL-10). A slight bell shaped
      inhibition of interferon gamma (IFN-gamma) was seen which was statistically
      significant (P < 0.05). In contrast, dexamethasone inhibited markedly the
      expression of all cytokines tested (IL-2, IL-4, IL-6, IL-10, IFN-gamma and TNF
      alpha) in dose-dependent fashion, reducing levels to near to background. Reverse
      transcription-polymerase chain reaction (RT-PCR) analyses showed that thalidomide
      inhibited selectively the expression of TNF-alpha and IL-6 mRNA, whereas
      dexamethasone inhibited mRNA levels of all cytokines examined. The data indicate
      that dexamethasone is a broad range immunosuppressant inhibiting all cytokines
      tested in a dose-dependent manner at the level of both secreted product and mRNA.
      Conversely, thalidomide selectively inhibits the production of IL-6 and TNF
      alpha. Due to their markedly different effects on cytokine production, and the
      fact that both drugs act at the level of transcription, we believe they influence
      separate pathways involved in cytokine gene regulation.

PMID- 9776475
TI  - Anti-arthritic effects of the novel dipeptidyl peptidase IV inhibitors TMC-2A and
      TSL-225.
AB  - We evaluated the immunopharmacological effects of two novel dipeptidyl peptidase
      IV (DP IV) inhibitors, TMC-2A [(2S,2S',2S'')-2-[2'-[2''-amino-3''-(-indol-3'''
      yl)-1''-oxopropyl]-1',2 ',3',4'-tetrahydro-6',8'-dihydroxy-7'-methoxyisoquinol-3
      yl-car bonylamino]-4-hydroxymethyl-5-hydroxypentanoic acid] and TSL-225
      (tryptophyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid). TMC-2A, produced
      by Aspergillus sp. A374, inhibited rat kidney DP IV uncompetitively, with a Ki
      value of 5.3 microM. In vivo, TMC-2A suppressed alkyldiamine (N,N-dioctadecyl
      N',N-bis(2-hydroxyethyl)propanediamine)-induced arthritis. We developed a
      chemically modified inhibitor, TSL-225, with potency similar to that of TMC-2A.
      TSL-225 inhibited DP IV uncompetitively, with a Ki value of 3.6 microM. TSL-225
      was also effective against adjuvant-induced arthritis. These results suggest that
      TMC-2A and its derivatives may have therapeutic potential for the treatment of
      inflammatory diseases such as rheumatoid arthritis.

PMID- 9776476
TI  - Taurine chloramine down-regulates the generation of murine neutrophil
      inflammatory mediators.
AB  - We previously reported that taurine chloramine (TauCl), a product of activated
      neutrophils, inhibits the generation of macrophage inflammatory mediators such as
      nitric oxide (NO), TNF-alpha, and PGE2. Taurine, the most abundant free amino
      acid in the cytosol of neutrophils, is chlorinated to form TauCl by the halide
      dependent myeloperoxidase (MPO) system. Under physiological conditions, TauCl
      reduces HOCl toxicity. In this study, we investigated the influence of TauCl on
      generation of oxygen free radicals, cytokines and eicosanoids by activated murine
      peritoneal neutrophils. We found that TauCl, but not taurine alone, inhibited the
      production of NO, prostaglandin E2, interleukin-6 and tumor necrosis factor
      alpha, in a dose-dependent manner. In contrast, the products of the respiratory
      burst, as measured by luminol-dependent chemiluminescence (LCL), were reduced by
      both taurine and TauCl. However, taurine affected LCL at higher concentrations
      and to a lesser extent than TauCl. The results of these studies suggest that
      TauCl decreases production of tissue-damaging inflammatory mediators and may
      regulate the balance between protective, microbicidal and toxic effect of
      neutrophils.

PMID- 9776477
TI  - Characteristic immunostimulation by angelan isolated from Angelica gigas Nakai.
AB  - The immunopharmacological characteristics of angelan, a polysaccharide purified
      from Angelica gigas Nakai, were investigated in relation to the specificity to
      immune cells. The treatment of angelan increased the expression of IL-2, IL-4, IL
      6, and IFN-gamma. The expression of IL-6 and IFN-gamma was rapidly augmented but
      that of IL-2 responded later. In the case of IL-4, angelan stimulated at early
      time after exposure but down-regulated thereafter. These results suggested that
      macrophages and natural killer cells involved in nonspecific immunity were
      primarily activated and helper T cells were secondarily affected by angelan.
      Angelan also had lympho-proliferative potential to B cells, specifically. The
      specificity of angelan was also elucidated in a cell fractionation experiment.
      The activated B cells by angelan also increased antibody production. The direct
      activation of B cells, macrophages, and accessory cells and the indirect
      activation of helper T cells coordinately increased immune functions such as in
      vitro and in vivo T-dependent immunization and antibody production. The
      experiment of host resistance to syngeneic tumors also showed that angelan
      potentiated the immune functions. In conclusion, angelan, a purified
      polysaccharide from an oriental herbal drug, showed characteristic
      immunostimulation, which was different from clinically used polysaccharides such
      as lentinan and PSK.

PMID- 9776478
TI  - B1 kinin receptor activity in pigs is associated with pre-existing infection.
AB  - Bradykinin (BK) and related kinins are potent inflammatory mediators produced
      during acute and chronic inflammation. The effects of these kinins are mediated
      via the stimulation of either a B2 or a B1 receptor. The B1 receptor is not
      normally present but its expression can be induced within 4 h by a variety of
      noxious stimuli, specifically, gram-negative bacteria or bacterial
      lipopolysaccharide (LPS) given to healthy animals. This study compared the
      cardiovascular response of healthy pigs and pigs diagnosed with a pre-existing
      spontaneously acquired infection to BK, a B2 receptor agonist, and des-Arg9-BK, a
      B1 receptor agonist. Eighty-eight percent of the animals diagnosed with an
      established infection based on a standardized clinical evaluation demonstrated
      increased sensitivity and responsiveness to des-Arg9-BK but normal responsiveness
      to BK and acetylcholine. In contrast, only 15% of healthy animals showed elevated
      responses to des-Arg9-BK. The response to des-Arg9-BK and BK in each group was
      characterised as B1 and B2, respectively, using the selective B1 and B2
      antagonists Lys0-Leu8-des-Arg9-BK and Hoe 140, respectively. This study
      demonstrates the existence and function of the B1 receptor in animals with a
      previously acquired infection. These observations lend validity to animal
      experiments with LPS infusion in order to model bacterial inflammation.

PMID- 9776479
TI  - Individual variations in lymphocyte-responses to glucocorticoids in patients with
      bronchial asthma: comparison of potencies for five glucocorticoids.
AB  - Glucocorticoids (GCs) are known to be effective for bronchial asthma, however, a
      considerable number of asthma patients fail to respond to GC despite the onset of
      serious side effects. Here we examined individual sensitivities to five
      clinically-used GCs in 40 asthma patients and 100 healthy subjects. Peripheral
      blood mononuclear cells (PBMCs) were isolated from these subjects, and their in
      vitro sensitivities to hydrocortisone, prednisolone, methylprednisolone,
      dexamethasone, and betamethasone were determined with a mitogen-assay procedure.
      The number of PBMCs positive to IL-2 receptors (IL-2Rs) as well as soluble IL-2R
      (sIL-2R) levels in serum were concomitantly measured in asthma patients, and
      relationships between these cytokine indices and PBMC-sensitivities to GCs were
      also examined. Large individual variations in GC IC50s have been observed in
      PBMCs from asthma subjects, especially in prednisolone IC50s (ranged from 1 to
      10,000 ng/ml). When compared with healthy subjects, asthma patients tend to show
      PBMC-resistance to prednisolone (p < 0.05). Moreover, potencies of
      methylprednisolone on PBMC-blastogenesis were > 10 times higher than those of
      prednisolone in both healthy subjects and asthmatics (p < 0.01). In asthma
      patients, IC50s of hydrocortisone, prednisolone and betamethasone against PBMC
      blastogenesis were significantly correlated with elevated percentages of IL-2R
      positive PBMCs (p < 0.05), while the IC50 of methylprednisolone showed no such
      correlation. sIL-2R levels did not correlate with IC50s of any of the GCs
      examined. Thus, the results showed that a part of asthma patients exhibited PBMC
      resistance to GCs, especially to prednisolone. Methylprednisolone potency was
      unexpectedly higher (> 10 times) than prednisolone potency. Our results also
      raised the possibility that PBMC-resistance to prednisolone in asthma may
      correlate with an increase in IL-2R positive PBMCs.

PMID- 9776480
TI  - Induction of apoptosis by dexamethasone in the B cell lineage.
AB  - The susceptibility to induction of apoptosis by the synthetic glucocorticoid,
      dexamethasone (Dex), was analysed at different stages of B cell maturation. Cells
      of the 70Z/3 pre-B cell line, expressing cytoplasmic mu chains, and LPS
      stimulated 70Z/3 cells, expressing surface IgM, were used as a model of
      differentiation of pre-B cells into immature B cells. Cell proliferation and cell
      cycle progression were similarly inhibited by Dex (100 nM) in both naive 70Z/3
      pre-B cells and in LPS-stimulated 70Z/3 cells. In contrast, Dex failed to affect
      apoptosis of naive 70Z/3 cells while it increased that of LPS-stimulated 70Z/3
      cells. Splenic mature B lymphocytes were highly susceptible to Dex-induced
      apoptosis since subphysiological doses (5 nM) increased the frequency of
      apoptotic cells to more than 80%. On the other hand, the treatment of B
      lymphocytes with LPS, which led to proliferation and differentiation into
      immunoblasts, decreased the susceptibility to Dex-induced apoptosis. These
      effects were mediated by the glucocorticoid receptor since they were abrogated by
      the RU 486 antagonist. The response of B cells to glucocorticoids is thus
      dependent on their stage of differentiation.

PMID- 9776482
TI  - Vitrification of in vitro produced bovine blastocysts: methodological studies and
      developmental capacity.
AB  - Methodological studies were undertaken to test the validity of a three-step
      vitrification procedure for bovine in vitro produced embryos using glycerol and
      ethylene glycol as cryoprotectants. Embryos were produced in a low-phosphate
      culture system (medium VT1 + 10% foetal calf serum) and vitrified at day 7 post
      insemination either in a mixture of 25% glycerol--25% ethylene glycol or a
      mixture of 10% glycerol--40% ethylene glycol. In the first mixture 67% (n = 283)
      of blastocysts were re-expanded after 72 h of culture and 53% were hatched while
      in the second one (n = 65) only 5% survived. The mean number of cells of the
      surviving blastocysts was correlated with the rate of survival (R2 = 0.47; P =
      0.0024). Embryo size (diameter < or > to 180 microm) did not influence blastocyst
      survival or cell number, but hatching rate was higher for embryos > 180 microm.
      Embryo survival, hatching rate and cell number 72 h post-warming were not
      affected by the mode of vitrification (direct plunging into nitrogen liquid or
      vitrification into nitrogen liquid vapour), the mode of preparation of the
      vitrification solutions (molar or molal basis) or by the concentration of
      galactose used as a diluent (0 to 0.85 M). Only one calf was born after transfer
      of 22 vitrified blastocysts. These results confirm the apparent lack of
      correlation for cryopreserved embryos between in vitro survival or hatching and
      viability after transfer.

PMID- 9776481
TI  - Effects of particulate and soluble (1-3)-beta-glucans on Ca2+ influx in NR8383
      alveolar macrophages.
AB  - Particulate and soluble (1-3)-beta-glucans are effective in preventing infections
      by enhancing macrophage and neutrophil functions. However, the mechanisms
      triggering these enhanced cellular responses are essentially unknown. We recently
      demonstrated that zymosan, a particulate (1-3)-beta-glucan receptor agonist,
      caused an influx of Ca2+ in NR8383 rat alveolar macrophages (AMs) and a resulting
      increase in intracellular Ca2+ (Zhang et al., J. Leukoc. Biol. 62 (1997) 341
      348). Since Ca2+ is important in mediating leukocyte responses, we investigated
      whether other (1-3)-beta-glucans also alter Ca2+ mobilization in AMs. Particulate
      and soluble (1-3)-beta-glucans derived from Saccharomyces cerevisiae were used in
      these studies. Like zymosan, particulate (1-3)-beta-glucan (WGPs) caused a
      concentration-dependent increase in [Ca2+]i, which was inhibited by removal of
      extracellular Ca2+ and by SKF96365, an inhibitor of receptor-operated Ca2+
      channels. When three different soluble (1-3)-beta-glucans, with molecular weights
      of approximately 11,000, 150,000, and 1,000,000 Da, were tested alone for effects
      on Ca2+ responses, the low molecular weight (1-3)-beta-glucan produced no effect
      and the intermediate and high molecular weight (1-3)-beta-glucans caused only a
      small increase in [Ca2+]i. Interestingly, however, all three soluble (1-3)-beta
      glucans could significantly reduce the Ca2+ responses induced by a subsequent
      exposure to either WGPs or zymosan. These results demonstrate that: 1)
      particulate (1-3)-beta-glucan activates Ca2+ influx in NR8383 macrophages through
      receptor-operated Ca2+ channels; 2) soluble (1-3)-beta-glucans do not strongly
      activate Ca2+ influx in these cells; and 3) soluble (1-3)-beta-glucans
      significantly inhibit Ca2+ influx induced by WGPs or zymosan. Soluble (1-3)-beta
      glucans are likely to prevent Ca2+ influx by competitively binding to the (1-3)
      beta-glucan receptors recognizing zymosan and WGPs. The smaller Ca2+ influx
      induced by soluble (1-3)-beta-glucans may represent only a partial activation of
      post-receptor signal transduction pathways necessary for inducing Ca2+ influx.

PMID- 9776483
TI  - Membrane integrity and fertilizing potential of cryopreserved spermatozoa in
      European mouflon.
AB  - There is a pressing need to develop and use assisted reproductive techniques in
      wildlife species living in small and captive groups. We evaluated the effect of
      freezing on membrane integrity and fertilizing capacity of European mouflon (Ovis
      gmelini musimon) spermatozoa collected during the breeding season. After thawing,
      the percentage of live spermatozoa, stained with fluorescein isothiocynate
      labeled Pisum Sativum agglutinin and propidium iodide, was 47% of which 19%
      showed intact acrosomal membrane. After culture in TCM 199 + 10% FCS, the number
      of live spermatozoa was significantly (P < 0.01) lower than in a medium with
      oviductal epithelial cells. The absence of oviductal cells decreased
      significantly the fertilization rates (P < 0.05), 24.0 vs. 63.1 with oviductal
      epithelial cells and 59.1 in vivo of in vitro matured ovine oocytes. Polyspermic
      fertilization rate of oocytes was lower (P < 0.05) with oviductal epithelial
      cells (1.6) than in absence of cells (12.8). However, the percentage of embryos
      that reached blastocyst stage was significantly higher in vivo than in vitro.
      These results provide interesting preliminary data for the development of genetic
      resource banks for European mouflon.

PMID- 9776484
TI  - Delayed luteolysis after intra-uterine infusions of nordihydroguaiaretic acid in
      the ewe.
AB  - Intrauterine administration of nordihydroguaiaretic acid (5 mg, bid. NDGA), an
      inhibitor of the enzyme 5-lipoxygenase, on days 10-14 of the oestrous cycle,
      maintained luteal function and delayed oestrus in the ewe. The duration (mean +/-
      SD) of the oestrous cycle in the treatment group (n = 4) was 24 +/- 1 days, which
      was significantly (P < 0.001) longer than that of 16 +/- 1 days in vehicle
      treated controls (n = 4); plasma progesterone concentrations were also
      significantly (P < 0.01) higher in the treatment group. On days 13 and 14 of the
      cycle (oestrus = Day 0) in the control group large pulses of 13,14-dihydro-15
      keto prostaglandin F2alpha (PGFM) were evident, with mean (+/- SD) maximum
      concentrations of 232.5 +/- 66 and 415 +/- 309 pg ml(-1), respectively. In the
      treatment group, however, concentrations of PGFM were below detection level (< 50
      pg ml(-1)). Similarly, in the control group, oxytocin release was highly
      pulsatile, with mean (+/- SD) peak concentrations of 21.8 +/- 5 and 18.5 +/- 6 pg
      ml(-1) on days 13 and 14, respectively; these were significantly (P < 0.01)
      higher than values of 7.6 +/- 3 and 6.1 +/- 3 pg ml(-1) in NDGA-treated ewes,
      where pulses were of relatively low amplitude. These results suggest that 5
      lipoxygenase products of arachidonic acid metabolism may be involved in the
      positive feedback mechanism between luteal oxytocin and uterine PGF2alpha during
      luteolysis in the ewe.

PMID- 9776485
TI  - Diurnal changes in light intensity inside the pregnant uterus in sheep.
AB  - Penetration of light into the pregnant sheep uterus was studied in 9 ewes,
      gestational ages 40 to 142 days (term 147 days). Light sensors were placed inside
      the pregnant horn and over the flank skin overlying the position of the uterine
      horn. To perform the experiments, the ewes were placed in a study cage outdoors
      and light sensors were connected to a luxometer. Simultaneous measurements were
      obtained from the intrauterine and the external sensors in the shade at noon. The
      amount of light detected inside the uterus increased with gestational age from
      two lux at 40 days to 51.1 +/- 16.5 (n = 5) lux at 142 days (0.2 and 5.4% of the
      amount of light detected at the maternal flank). Measurements through the 24 h
      were done in four pregnant ewes at 142 days gestation under natural photoperiod
      (13.5 light:10.5 dark). In these experiments, the intensity of intrauterine light
      changed through the 24 h, reflecting the changes in the intensity of the
      sunlight. Maximal intrauterine light values were observed at noon, corresponding
      to 4.7% of incident light. Small but detectable values were observed at 0900 and
      1800 h. Our data show that, at mid gestation, light reaches the pregnant uterus
      and that, at late gestation, changes in intrauterine lighting throughout the 24 h
      are present reflecting the changes in external daylight. Therefore the sheep
      fetus is exposed to light-dark transitions at dawn and dusk, and to a peak of
      light at midday.

PMID- 9776486
TI  - Effects of level of food intake on ovarian follicle number, size and
      steroidogenic capacity in the ewe.
AB  - The effect of high (H) or low (L) levels of food intake, during the preceding 4
      weeks, on ovarian follicle numbers and steroidogenic capacity were investigated
      in groups of 12 adult Scottish Blackface ewes. Ewes of the two treatments had
      similar levels of body condition at the time of study but there was a twofold
      difference in levels of food intake. Ovaries were surgically removed on day 11 or
      12 of the oestrous cycle (luteal phase; n = 6 per nutritional treatment) or at 30
      h after injection (i.m.) of prostaglandin F2alpha analogue on day 11 or 12 of the
      cycle (follicular phase; n = 6 per nutritional treatment). Ovarian follicles > 1
      mm diameter were dissected out and incubated individually for 2 h at 37 degrees
      C, in 1 ml of medium 199 which was then assayed to determine concentrations of
      oestradiol and testosterone. There were significantly more small follicles (1-2.5
      mm diameter) in (H) than (L) ewes (P < 0.05) but no treatment difference in the
      numbers of large follicles (> 2.5 mm diameter) during either phase of the cycle
      and no difference in the mean diameters (mm) of the two largest follicles in each
      animal. However, although there were higher rates of synthesis of both oestrogen
      (P < 0.05) and testosterone (P < 0.01) in the large follicles of (L) ewes as
      compared with (H) ewes, there was a lower oestrogen/testosterone ratio in (L)
      than (H) follicles which may indicate a lower level of aromatase activity in (L)
      follicles. It is concluded that the effects of level of food intake on ovulation
      rate are expressed through differences in late stages of follicle development,
      probably through effects on the intrafollicular steroid milieux.

PMID- 9776487
TI  - The effect of environment on plasma cortisol and beta-endorphin in the parturient
      pig and the involvement of endogenous opioids.
AB  - Previous work has indicated that plasma cortisol increases during farrowing in
      the pig suggesting increasing physiological stress. The aim of this study was to
      determine changes in plasma cortisol and beta-endorphin over farrowing in the pig
      to obtain a more detailed profile of pituitary and adrenal release at this time
      and also to investigate the involvement of endogenous opioids in the mediation of
      the HPA axis. Indwelling jugular catheters were implanted, under general
      anaesthesia, in 31 Large White x Landrace gilts approximately 15 days before the
      expected parturition day (EPD). Gilts were moved into either a farrowing crate,
      without straw (n = 15), or a straw-bedded pen (n = 16) 5 days before the EPD.
      Samples were taken during the pre-farrowing period and then during farrowing
      itself. At 7.5 min after the birth of the first piglet (BFP), gilts either
      received naloxone, an opioid antagonist, (1 mg kg(-1) body weight, i.v.) or a
      control dose of saline. Plasma beta-endorphin increased following the BFP but
      remained fairly constant over the third and fourth hour of farrowing. Plasma
      cortisol continued to increase over the 4 h following the BFP. Changes seen in
      these hormones were generally insensitive to the environment and there was little
      evidence of opioid mediation of the HPA axis at parturition. From these results
      it is suggested that certain aspect(s) of parturition itself stimulate the HPA
      axis. However it is unknown if the rise in plasma cortisol is a result of some
      stress-inducing factor of the parturition process or whether it reflects a
      metabolic function. The study also demonstrates the lack of any inhibitory
      mediation of the HPA axis by endogenous opioids at parturition.

PMID- 9776488
TI  - Influence of lactation length and feed intake on reproductive performance and
      blood concentrations of glucose, insulin and luteinizing hormone in primiparous
      sows.
AB  - Twenty-four pregnant gilts were assigned to four experimental treatments in a 2 x
      2 factorial arrangement. The first factor was lactation length (12 vs. 21 days)
      (LL); the second factor was a provided amount of diet (FF, full feeding vs. low,
      2 kg/day). The same diet (1% lysine and 3.27 Mcal ME/kg) was used from farrowing
      to 1 day after weaning. Sow body weight, backfat thickness (BF), litter weights,
      and blood samples were measured prior to and 1 day after weaning. Sows were
      monitored for estrous once daily in the presence of a boar until 35 days after
      weaning or until estrous was detected. Average feed intake during lactation
      (ADFI) was 1.9 (low) and 4.0 (FF) kg/day. ADFI among individual sows varied from
      1.8 to 4.9 kg/day. Positive effects of both LL and feed intake treatments were
      found (P < 0.05) on sow body weight loss, backfat loss, glucose concentrations,
      mean luteinizing hormone (LH) concentrations, and LH pulse frequency prior to
      weaning, and farrowing-to-estrous interval. Greater concentrations of insulin
      prior to weaning were associated only with feed intake treatment (P < 0.05). No
      interactions between LL and feed intake treatments were found in any measures
      except for sow body weight loss. Using regression analysis, greater lactation
      feed intake was associated with greater concentrations of insulin and glucose,
      greater LH pulse frequency prior to weaning and shorter farrowing-to-estrous
      interval in both LL treatments. We suggest that greater feed intake during
      lactation improves farrowing-to-estrous interval through LH release regardless of
      LL treatment.

PMID- 9776490
TI  - Proposal for an urgency classification in cardiac surgery.

PMID- 9776489
TI  - Artificial insemination in Callithrix jacchus using fresh or cryopreserved sperm.
AB  - Assisted reproductive techniques are needed urgently to facilitate the captive
      breeding of many New World primate species which are endangered in the wild and
      to assist the effective genetic management of small colonies. A protocol was
      devised for artificial insemination in the common marmoset, Callithrix jacchus,
      using ejaculated sperm obtained by vaginal washing after copulation. A double
      insemination protocol was employed, with the first insemination taking place the
      day before ovulation was expected to occur and the second 48 h later. All six
      females inseminated with fresh ejaculated sperm became pregnant, delivering a
      total of 16 offspring at term. The gestation lengths and litter sizes were not
      statistically different from those observed in pregnancies following natural
      mating. The insemination protocol was adapted for use with cryopreserved
      ejaculated sperm by including an additional insemination on the day of expected
      ovulation, to take into account differences in the capacitation time of frozen
      thawed sperm compared to fresh sperm. Three out of six females inseminated
      according to this triple insemination schedule, conceived, although one female
      subsequently resorbed twin foetuses approximately 100 days later. The remaining
      two pregnant females delivered four babies at term, one singleton and one set of
      triplets. In the final group, six females were inseminated with low doses of
      cryopreserved epididymal sperm using the same triple insemination protocol used
      for frozen-thawed ejaculated sperm. One female conceived, delivering triplets.

PMID- 9776491
TI  - Reversal of ventricular dilatation after correction of aortic incompetence:
      mechanical prosthesis compared with biological procedures.
AB  - BACKGROUND: The aim of the study was to compare early differences in reversal of
      LV dilatation between patients with mechanical prosthesis = group A (n = 51:
      Carbomedics = 40, Tekna/Edwards = 11) and biological procedures = group B (n =
      75: pulmonary autograft = 36, aortic valve repair = 29, homograft = 10). METHODS:
      Since 1,990,126 consecutive patients younger than 50 years who had surgical
      correction of isolated aortic incompetence underwent echocardiographic
      examinations preoperatively, at discharge, and at one-year follow-up. Left
      ventricular (LV) diameters were measured (LVEDD, LVESD) and matched to body
      surface area (LVESDI, LVEDDI and fractional shortening (FS) was calculated.
      Aortic peak flow velocities were assessed by Doppler technique and gradients were
      calculated. RESULTS: There were no significant differences preoperatively in
      aortic incompetence, NYHA classification, LVEDDI, LVESDI, and FS. In group B
      there was a significant decrease of LVESDI (p < 0.002) and LVEDDI (p < 0.001) but
      no change in FS at discharge. In group A a significant reduction of FS (p < 0.05)
      without any significant changes in LV size was observed. No patient died
      perioperatively or during the first year. At one-year follow-up (complete in
      97.6% patients) there were no significant differences in LV diameters but group B
      had better ventricular function (p < 0.05) resulting in better NYHA
      classification (p < 0.05). Only group B had normal aortic valve gradients at
      discharge and at follow-up (A: 25.2 +/- 4.3 vs B: 10.2 +/- 2.4 mmHg).
      CONCLUSIONS: Normal aortic valve gradients in patients after aortic valve repair
      or allograft replacement for chronic aortic incompetence lead to early recovery
      from ventricular dilatation and significantly better ventricular function at
      discharge. One year postoperatively they had improved ventricular function and
      NYHA class in comparison with patients in whom a mechanical prosthesis was
      implanted.

PMID- 9776492
TI  - The Ross operation: do native aortic, native pulmonary, and homograft pulmonary
      valve size and form differences influence results?
AB  - BACKGROUND: The pulmonary autograft approaches the ideal aortic valve substitute
      but numerous technical modifications are debated. The valves involved often
      differ in diameter and shape of the recipient annulus. We previously reported
      simplified surgical rules and early results of 52 patients and here we extend the
      report to 76 patients and analyze the mid-term results with respect to valve
      mismatch. METHODS: We studied the influence of geometric discrepancies. Valve
      regurgitation and gradient are compared for size discrepancies up to or more than
      3 mm between recipient annulus and pulmonary autograft. The normal tricuspid
      recipient aortic annulus is compared with the flat circular redo-prosthetic or
      bicuspid annulus. Patients with plication of the aortic annulus and remodeling of
      the distal aorta are reviewed, and lastly donor homograft to pulmonary autograft
      discrepancies up to and more than 3 mm are compared. RESULTS: The results were
      comparable in all groups and no significant differences were observed.
      CONCLUSION: The pulmonary autograft operation may be simplified, with good
      results at the least in the first year despite operative tailoring due to valve
      discrepancies.

PMID- 9776493
TI  - Preoperative left-ventricular ejection fraction does not influence the
      improvement in quality of life after coronary artery bypass surgery.
AB  - Coronary artery bypass grafting (CABG) is an established treatment for angina
      pectoris which conveys relief of chest pain and improved physical performance.
      However, increased survival has only been observed in selected subgroups of
      patients with advanced coronary artery disease, particularly in the presence of
      depressed left-ventricular ejection fraction (LVEF). It is therefore of interest
      to study whether the outcome in terms of quality of life (QoL) is also more
      favorable in candidates with depressed LVEF. All patients who underwent CABG
      without concomitant valve surgery in western Sweden between 6.1988 and 6.1991 (n
      = 2121) were sent questionnaires on QoL involving 3 different instruments, the
      Physical Activity Score, the Nottingham Health Profile, and the Psychological
      General Well-being Index. They were submitted before surgery and 3 times in the 2
      years thereafter. QoL was improved on all postoperative occasions. The degree of
      improvement was not associated with preoperative LVEF for any of the instruments.
      The postoperative Physical Activity Score was associated with preoperative LVEF.
      The other instruments showed no such association with LVEF. The improvement in
      QoL during 2 years after CABG is not dependent on the LVEF determined prior to
      operation. Self-estimated physical abilities are postoperatively associated with
      preoperative LVEF whereas health-related QoL and general well-being are not.

PMID- 9776494
TI  - Neuropsychological changes after cardiopulmonary bypass for coronary artery
      bypass grafting.
AB  - BACKGROUND: An alarming incidence (1% to 83%) of neuropsychological dysfunction
      has been reported after operations using cardiopulmonary bypass (CPB). The
      present clinical study re-evaluates these complications with current CPB
      technology in a strictly selected low-risk group of coronary artery bypass (CABG)
      patients. METHODS: 76 CABG patients, without history of stroke or internal
      carotid artery stenosis, were examined before, 5 days after, and 2 months after
      surgery. A neuropsychological test battery was employed according to the
      "Statement of Consensus on Assessment of Neurobehavioral Outcomes after Cardiac
      Surgery". Tests include the Block Design Test (problem-solving strategies,
      recognition and analysis of forms), the Trail Making Test (cognitive achievement
      at speed), and the Digit Span Test (short-term memory and memory of figures).
      RESULTS: Both postoperative test scores were not significantly decreased as
      compared to preoperative values. In contrast, neuron specific enolase (NSE) and
      S100 b protein, biochemical markers of cerebral injury, increased markedly during
      and immediately after surgery (NSE preop.: 7.07 +/- 2.40 ng/ml, 1 h postop.:
      13.64 +/- 4.50 ng/ml, p < 0.001; S100 b preop.: 0.04 +/- 0.07 ng/ml, after
      crossclamp: 0.90 +/- 0.69 ng/ml, p < 0.001). One patient displayed postoperative
      transitional syndrome, another patient suffered from transitory paresis and
      hypesthesia of the left arm, which disappeared during hospital stay. CONCLUSIONS:
      Biochemical markers demonstrate significant postoperative cerebral injury during
      and immediately after CPB. However, CPB for CABG does not lead to marked
      impairment of neuropsychological scores, and clinically relevant neurological
      findings were observed in one patient only.

PMID- 9776495
TI  - Left-ventricular expression of interleukin-6 messenger-RNA higher in idiopathic
      dilated than in ischemic cardiomyopathy.
AB  - During end-stage heart failure, plasma levels of interleukin-6 (IL6) are
      elevated. This cytokine exerts a negative inotropic influence on the myocardium.
      The production site of IL6 is unclear. We examined the hypothesis that IL6 in end
      stage heart-failure patients is produced in the myocardium itself and is
      differentially regulated according to etiology. Cardiac tissue was obtained from
      27 patients (idiopathic dilated cardiomyopathy, (DCM) 9/6 m/f, age 46 +/- 14 y;
      ischemic cardiomyopathy (ICM), 11/1 m/f, age 55 +/- 8 y) at the time of
      transplantation. The tissue was subjected to IL6 Northern-blot analysis. Signals
      were quantified by densitometric scanning after normalization to G3 PDH mRNA.
      Data were compared by Mann-Whitney test between DCM and ICM patients, divided by
      chamber origin. IL6 transcripts were found in all patients. In DCM, left
      ventricular IL6 mRNA expression was higher than in ICM (p = 0.006). Median right
      ventricular as well as left- and right-atrial IL6 mRNA expression was not
      significantly different in both groups. In summary, in end-stage heart failure,
      IL6 mRNA is consistently expressed in the myocardium. Left-ventricular expression
      is higher in DCM than in ICM. These data support the concept of a potentially
      reversible inflammatory component in the etiology of DCM which is more pronounced
      than in patients with ICM of comparable clinical severity.

PMID- 9776496
TI  - Usefulness of the QTc interval in predicting acute allograft rejection.
AB  - BACKGROUND: Endomyocardial biopsy (EMB) is the gold standard for detecting
      cardiac allograft rejection. However, EMB is invasive, costly, and unsuitable for
      frequent monitoring. Recent studies have shown that acute allograft rejection
      causes ventricular conduction disturbances. Therefore we tested the hypothesis
      that the electrocardiographic QTc interval correlates with the histopathologic
      degree of allograft rejection. METHODS: Between January 1994 and April 1997, 65
      adult cardiac allograft recipients (mean age 52.1 +/- 1.7 years) were studied
      from transplantation until hospital discharge. During EMB, a 12-lead
      electrocardiogram was obtained. In grading acute allograft rejection, we used
      both the Texas Heart Institute (THI) scale and the International Society for
      Heart and Lung Transplantation (ISHLT) scale. 212 paired biopsy specimens and QTc
      intervals (mean 3.3 per patient) were obtained. We considered an increase of more
      than 10% of the QTc interval a rejection. RESULTS: Of the biopsy specimens 177
      showed no or mild rejection (THI grade 0-5; ISHLT grade O-IIIA), and 35 showed
      moderate to severe rejection (THI grade 6-10; ISHLT IIIA-IV). The mean QTc
      interval was 449 +/- 2 msec for the first group and 517 +/- 11 msec for the
      second group (p = 0.0001). The correlation between the biopsy grades and the
      percentage of the changes in the QTc interval was r = 0.73 (p = 0.001). The QTc
      interval had a sensitivity of 86% (30/ 35) in predicting rejection and a
      specificity of 88% (1551177) in predicting the absence of rejection. CONCLUSIONS:
      Determination of the QTc interval is an accurate, noninvasive means of detecting
      acute cardiac rejection. Adoption of QTc testing may allow EMB to be used less
      frequently and more selectively.

PMID- 9776497
TI  - Response of the cellular immune system to cardiopulmonary bypass is independent
      of the applied pump type and of the use of heparin-coated surfaces.
AB  - BACKGROUND: Cardiopulmonary bypass (CPB) is associated with an activation of
      leukocytes. The extent of this activation was thought to depend on the applied
      CPB-circuit set-up. The present study comparatively evaluated the effect of
      roller pump, centrifugal pump, and uncoated and heparin-coated surfaces. METHODS:
      73 patients were included, randomly assigned to 3 groups. In group A a roller
      pump was used, in group B a centrifugal pump, and in group C a centrifugal pump
      together with Carmeda heparin-coated surfaces. The quantitative (cell count) and
      the qualitative changes of leukocyte populations (subpopulations and expression
      of the CD126-, HLA-DR-, CD45 RO-, CD71 antigens) was comparatively analysed
      before, during, and following CPB. RESULTS: Groups A and B did not differ in
      leukocyte counts and the differences between groups B and C were restricted to
      single time points. Neither groups A and B, nor groups B and C differed
      significantly in the relative distribution of lymphocyte subpopulations or in the
      percentage of CD126+, HLA-DR+, CD45 RO+ and CD71+ leukocyte subpopulations.
      CONCLUSIONS: CPB affects the cellular immune system; however, this effect seems
      to be a physiological reaction, independent of the applied CPB circuit system.

PMID- 9776498
TI  - Are in-vitro platelet function tests useful in predicting blood loss following
      open heart surgery?
AB  - BACKGROUND: We investigated the suitability of two commercially available in
      vitro bleeding tests (IVBT), the PFA-100 and the Hepcon HMS, to predict blood
      loss following operations with extracorporeal circulation (ECC) and compared them
      with conventional coagulation studies. METHODS: In 40 patients subjected to
      elective open heart surgery with ECC a blood sample was taken before and after
      ECC to measure platelet count, prothrombin time, aPTT, D-dimers, fibrinogen, and
      PFA-100 and Hepcon HMS data. The postoperative blood loss was recorded hourly
      until removal of drains. RESULTS: A significant correlation was found between
      total blood loss (250-1750 ml) and the preoperative PFA-100 (r = 0.41, p =
      0.022), the preoperative platelet count (r = -0.42, p = 0.007), the preoperative
      D-dimer concentration in the plasma (r = 0.41, p = 0.01), and duration of ECC (r
      = 0.35, p = 0.044). There was no significant correlation between blood loss and
      the Hepcon HMS system. CONCLUSIONS: Although a significant correlation was found
      between blood loss and the PFA-100 IVBT, the practical value of these tests in
      the clinical situation is limited due to a great variability in individual
      results.

PMID- 9776499
TI  - Endothelin-A receptor antagonist BQ123 protects against myocardial and
      endothelial reperfusion injury.
AB  - BACKGROUND: This study was designed to investigate the effects of the selective
      endothelin-A receptor antagonist BQ123 on myocardial and endothelial function
      after reversible deep hypothermic ischemia and reperfusion. METHODS: Isogenic
      intra-abdominal heterotopic heart transplantation was performed in Lewis rats.
      After one hour of cold ischemic preservation reperfusion was started after
      application of either saline vehicle or BQ123 (1 micromol/L). Left-ventricular
      pressure-volume relations and myocardial blood flow were assessed after one and
      24 hours of reperfusion. Responses to endothelium-dependent vasodilator
      acetylcholine and endothelium-independent vasodilator sodium nitroprusside were
      also determined. RESULTS: BQ123 significantly improved myocardial contractility,
      as indicated by the leftward shift of the systolic pressure-volume relation and
      significantly increased myocardial blood flow during early reperfusion (p <
      0.05). Although myocardial function and baseline myocardial blood flow were
      similar in both groups after 24 hours of reperfusion, endothelium-dependent
      vasodilatation was still significantly higher in the BQ123 group (p < 0.05).
      CONCLUSIONS: These results suggest that endothelin-A receptor antagonists may be
      useful in reducing ischemia/reperfusion injury after heart transplantation by
      preservation of myocardial and endothelial function.

PMID- 9776500
TI  - Exclusion of lumbar arteries by aortic endovascular grafts: can angiography
      demonstrate sealing characteristics?
AB  - BACKGROUND: This study evaluates sealing characteristics of two designs of
      endovascular grafts by angiographic demonstration of exclusion of porcine lumbar
      arteries. METHODS: 6 endovascular grafts (3 self-expandable with integrated
      polyurethane wall versus 3 nitinol structures covered with polyester fabric) were
      implanted in 6 porcine aortae. Perfusion of lumbar arteries was assessed by
      angiography after implantation and by angiography and dissection at graft
      explantation after 4 +/- 2 months. Tissue healing was evaluated by light and
      scanning electron microscopy. RESULTS: Immediate exclusion of the lumbar arteries
      was achieved in 14/31 vessels (12 by polyurethane grafts and 2 by polyester
      grafts, p < 0.001). Follow-up angiography and dissection at explantation revealed
      perfusion of 30/31 lumbar arteries with a collateral network in most cases.
      Another reason for reperfusion of initially excluded branches was distention of
      the polyurethane grafts with resulting shortening allowing reperfusion of 8 of
      the 31 originally covered branches. Histological examination revealed a complete
      neointimal lining and a tight contact between endovascular grafts and aorta.
      CONCLUSIONS: The immediate angiographic demonstration of exclusion of lumbar
      arteries predicts sealing characteristics of endovascular grafts. Later
      angiographic reappearance is due to development of a collateral network and
      possible shortening of self-expandable devices.

PMID- 9776501
TI  - Continuous, less invasive, hemodynamic monitoring in intensive care after cardiac
      surgery.
AB  - A pulse-contour-based method for continuous measurement of cardiac output (CO)
      and systemic vascular resistance (SVR) was tested and arterial thermodilution,
      used for calibration, was compared to pulmonary artery thermodilution. In 30
      patients CO and SVR were measured by pulse contour analysis (COpc, SVRpc) 270
      times in 24 h and compared to arterial (COart, SVRart) and pulmonary arterial
      (COpa, SVRpa) thermodilution measurements. The mean difference between COpa and
      COart was 0.26 L/min (3.6%) with a standard deviation (SD) of 0.7 L/min, the
      correlation coefficient was 0.96, and the coefficient of variation was 5.0% and
      5.9% respectively. COpc did differ from COpa by 0.11 L/min (1.5%, SD = 0.6 L/min)
      and from COart by 0.15 L/min (2.1%, SD = 0.7 L/min). Correlation of COpc with
      COpa was 0.91, correlation of COpc with COart was 0.90. SVRpc did correlate with
      SVRpa, a coefficient of 0.94, and with SVRart, a coefficient of 0.92. Mean COpc
      and SVRpc did not differ significantly from COpa or COart and SVRpa or SVRart
      during the 24 h study period. It is concluded that COart correlates well with
      COpa and can be used to calibrate COpc. COpc and SVRpc agree with thermodilution
      based CO and SVR without recalibration for 24 hours.

PMID- 9776502
TI  - Western diet, early puberty, and breast cancer risk.
AB  - The typical high fat, low fibre diet of the industrialised West, particularly
      when associated with inadequate exercise, is likely to advance the onset of
      puberty. This will manifest in girls as an earlier menarche, earlier onset of
      breast development, and an earlier growth spurt. Both earlier menarche and adult
      tallness are markers of increased risk to breast cancer. Earlier menarche in the
      West is usually associated with earlier onset of hyperinsulinaemia, and multiple
      case-control studies report that hyperinsulinaemia too is a marker of increased
      breast cancer risk. Although the Western diet is linked both to earlier menarche
      and also to earlier hyperinsulinaemia, the mechanism involved is not necessarily
      the same. While menarche is likely to be triggered by a threshold level of
      fatness, manifestation of insulin resistance is genetically-determined and
      strongly influenced by the fatty acid profile of the diet. The putative
      mechanisms by which they influence mammary carcinogenesis also differ. Early
      menarche is reported to be associated with a raised oestradiol level persisting
      into early adult life. On the other hand, hyperinsulinaemia is commonly
      associated with abnormal aromatase activity in the ovaries. In addition, the
      concomitant increase in bioactive levels of insulin-like growth factor-I may
      synergise with oestrogen in stimulating proliferative activity in mammary
      epithelium. Dietary modification and exercise regimens are proposed in families
      at high risk to breast cancer. The measures have been shown to reduce insulin
      levels in both children and adults, and serial monitoring of insulin and sex
      steroid levels could be used to detect a metabolic-endocrine effect.

PMID- 9776503
TI  - Fibrotic focus in infiltrating ductal carcinoma of the breast: a significant
      histopathological prognostic parameter for predicting the long-term survival of
      the patients.
AB  - The presence of fibratic fows (FF) in infiltrating ductal carcinoma (IDC) has
      been shown to be an important histological factor associated with high tumor
      aggressiveness, or early tumor recurrence or death. However, the
      clinicopathological significance of FF for predicting the long-term survival of
      the patients with IDC has not been fully investigated. In order to elucidate this
      aspect, we divided 140 IDCs with at least 10 years of follow up into tumors with
      FF and those without. IDC with FF showed significantly higher histologic grade
      (P=0.02), higher frequency of tumor necrosis (P=0.02), higher frequency of cases
      with more than three positive lymph node metastases (P=0.04), higher T
      classification (P=0.009), and higher pathological stage (P=0.0002) than those
      without FF. Relative risk (RR) of tumor recurrence and death was significantly
      higher in tumors with FF than in those without (RR=4.5, P < 0.00001 and RR=5.6, P
      < 0.00001, respectively). In cases of early stage cancer (stages I, IIA, and
      IIB), or in those with less than four lymph node metastases, IDCs with FF
      demonstrated a significantly higher risk than those without. Multivariate
      adjustments for other pathological factors did not change the RRs significantly.
      These results indicate that in long-term follow up the presence of FF is a
      significant prognostic parameter for IDC, and therefore strongly suggest that
      IDCs must be divided into those with and without FF.

PMID- 9776504
TI  - Modulating effect of lonidamine on response to doxorubicin in metastatic breast
      cancer patients: results from a multicenter prospective randomized trial.
AB  - Previous results from our preclinical studies have shown that lonidamine (LND)
      can positively modulate the antiproliferative activity of doxorubicin (DOX) on
      breast cancer cell lines. To evaluate the effect of LND in a clinical setting, a
      multicenter randomized trial was carried out on patients with advanced breast
      cancer. From September 1991 to July 1993, 181 patients were enrolled in the trial
      and received an initial treatment of DOX at 75 mg/m2 for 3 cycles. The 137
      patients who reached complete remission, partial remission, or stable disease
      were randomized to receive either DOX alone (75 mg/m2 day 1) (arm A) or DOX plus
      LND (600 mg orally/day) (arm B). The patients enrolled in the two arms were
      fairly homogeneous in terms of major clinical characteristics. Toxicity was
      similar in both arms except for myalgia: WHO grade > or=2 was observed in 57% of
      arm B patients. Overall response rate to DOX + LND was 50% and to DOX alone 38%
      in evaluable patients, and 48% vs 37% in all registered patients, as determined
      by an intention-to-treat analysis. The differences did not reach statistical
      significance. Conversely, in agreement with previous findings, we observed a
      significant difference in response rate in the subgroup of patients with liver
      metastases, regardless of the extent of hepatic involvement (DOX + LND 68% vs DOX
      33%, p=0.03). This observation makes LND an important tool in association with
      anthracyclines in the treatment of this subgroup of patients.

PMID- 9776505
TI  - Estrogen receptor negative and progesterone receptor positive primary breast
      cancer: pathological characteristics and clinical outcome. Institut Curie Breast
      Cancer Study Group.
AB  - The expression of estrogen (ER) and progesterone (PgR) receptors was analyzed in
      a retrospective series of 3000 patients who had operable primary breast cancer.
      Patients were stratified according to ER and PgR status and the study was focused
      on the two groups (ER-PgR+ and ER-PgR-) of patients whose tumors contained low
      levels of ER (< 15 fmol/mg protein), regarding potential response to endocrine
      therapy. The comparison of clinical or histological characteristics between ER
      PgR+ and ER-PgR- patients was analyzed as well as the disease-related death and
      survival. The mean follow-up was 86.3 months. Among the 529 ER-patients, 62 were
      PgR+ (12%), whereas 467 were PgR- (88%). The ER-PgR+ and ER-PgR- populations
      represented 2% and 15.6% of the overall population, respectively. In ER- tumors,
      the PgR status was significantly related to: age, menopausal status, tumor size,
      SBR grade, and histological type, but not to the type of surgical treatment or to
      lymph node involvement. ER-PgR+ tumors had smaller size (64% T1 vs 43%) (p=0.004)
      and were more frequently grade I (28% vs 12%) than ER-PgR- tumors (p < 0.001). In
      addition, the patients with ER-PgR+ tumors were significantly younger (49.4 years
      vs 58.4 years; p < 0.0001), and were more frequently premenopausal (76% vs 36%, p
      < 0.001). The disease-free interval and the metastasis-free survival tended to be
      worse for ER-PgR- than for ER-PgR+ patients, but the difference was not
      statistically significant at 10 years. However, a small but significant
      difference in overall survival, in favor of the PgR+ group, was observed between
      the two groups during the first 5 years (p=0.03). We conclude that in combination
      with ER, PgR status defines a group of patients with clinical and biological
      specificity, which could be considered for specific endocrine therapy.

PMID- 9776506
TI  - Modulation of estrogen receptor gene expression in human breast cancer cells: a
      decoy strategy with specific PCR-generated DNA fragments.
AB  - Transcriptional activity of human estrogen receptor (hER) gene was modulated by
      competition with double-stranded PCR-generated DNA fragments (decoys) that
      contain 5' upstream sequences of the hER gene. Two DNA fragments belonging to the
      P1 canonical promoter and the P3 distal promoter, 120 and 102 bp in size
      respectively, were produced by PCR and directly transfected in MCF7 breast cancer
      cells. After 24 hours transfection, RT-PCR analysis revealed that the 120 bp
      decoy significantly reduced the expression of the ER gene and estrogen responsive
      genes (PR and c-myc), whereas the 102 bp decoy increased the ER mRNA level. An ER
      unrelated PCR product, used as control, had no activity. The biological activity
      of these ds DNAs was related to their high stability, binding affinities, and
      lack of cytotoxicity. These findings suggest that such PCR product decoys may be
      a non-antisense tool to analyze putative regulatory sequences and to study the
      function of DNA-binding transcription factors.

PMID- 9776507
TI  - High-dose therapy with peripheral blood stem cell (PBSC) support using an
      innovative mobilization regimen in patients with high-risk primary or
      chemoresponsive metastatic breast cancers.
AB  - High-dose therapy followed by peripheral blood stem cell (PBSC) support was
      performed in 29 patients with primary high-risk (Group I) or chemoresponsive
      metastatic (Group II) breast cancer patients. Group I patients had received PBSC
      mobilization within 4 weeks of modified radical mastectomy. Group II patients had
      to achieve minimal residual disease (MRD) by induction chemotherapy before being
      considered eligible for PBSC mobilization and high-dose therapy. An innovative
      FE120C regimen (5-FU 600 mg/m2, i.v., day 1; epirubicin 120 mg/m2, i.v., day 1;
      cyclophosphamide 600 mg/m2, i.v., day 1) plus G-CSF (300 microg/day, subcutaneous
      injection for 9 days, from day 4 post-FE120C) was used to mobilize PBSCs. After
      high-dose CTCb (cyclophosphamide 6,000 mg/m2, thiothepa 500 mg/m2, carboplatin
      800 mg/m2, in 4 days), patients received PBSC infusion and daily C-CSF 300 microg
      subcutaneous injection. There were 19 and 16 patients enrolled into Group I and
      Group II, respectively. Ten of the Group II patients had achieved minimal
      residual disease (MRD) after induction chemotherapy. The median numbers of
      mobilized total CD34 + cells for Group I and Group II patients were 27.3 (9.2 to
      114.1) x 10(6)/kg and 17.1 (5.9 to 69.1) x 10(6)/kg respectively. The median time
      to neutrophil recovery (ANC > or = 500/microL) was 8 and 9 days in Group I and
      II, respectively. The median time to platelet recovery (> or = 50,000/microL) was
      10 and 15 days in Group I and II, respectively. No major treatment-related
      toxicities were noted. In Group I, 13 out of 19 patients (68.4%; 43-87%, 95%
      C.I.) remained recurrence-free with a median follow-up of 31 months (6 + to 55 +
      months). In Group II, 3 out of 10 patients (30%; 7-65%, 95% C.I.) remained
      progression-free at 33 +, 35 +, 39 + months from induction therapy. We suggest
      that the FE120C plus G-CSF is an effective and innovative regimen for PBSC
      mobilization in breast cancer patients, and high-dose CTCb therapy with PBSC
      support is a safe and well-tolerated treatment modality.

PMID- 9776508
TI  - Fractal analysis of mammographic lesions: a prospective, blinded trial.
AB  - Mammography has become the mainstay of breast cancer screening. However,
      widespread mammography has led to an increase of the number of breast biopsies
      done for benign disease. Therefore, a method to better discriminate benign from
      malignant lesions is needed. Fractal analysis is a mathematical method which can
      quantify complex shapes. It has been previously shown retrospectively that the
      composite fractal dimensions, D, of malignant mammographic masses is higher than
      for benign lesions. A prospective study of 75 patients who were recommended to
      undergo needle localized breast biopsy by independent radiologists had the
      composite D calculated. Fractal analysis was done without knowledge of the biopsy
      results. The mean composite D of malignant lesions was higher than benign
      lesions, 2.545+/-0.067 vs. 1.936+/-0.144 (p=0.00004). Calculation of a receiver
      operating characteristic curve showed that a cutoff value of 2.067 had a 100%
      sensitivity and 63 % specificity (i.e., false positive rate of 37%). Mean D for
      fibroadenomas was 2.087+/-0.054, fibrocystic disease was 1.877+/-0.167, DCIS was
      2.261+/-0.069, and invasive cancer was 2.634+/-0.039 (1-way ANOVA, p=0.00007).
      These data imply that fractal analysis may be beneficial in discriminating
      between benign and malignant lesions. However, further study in a larger number
      of patients with a variety of lesions is needed.

PMID- 9776509
TI  - Evaluation of in vitro chemosensitivity of antitumor drugs using the MTT assay in
      fresh human breast cancer.
AB  - Practical criteria were developed in this paper for the purpose of evaluating
      chemosensitivity of fresh human breast cancer by the MTT assay. The survival
      rates at maximum inhibition (Imax %) and the concentrations of drugs which caused
      fifty percent reduction in absorbance compared to baseline values (IC50) of 175
      samples of 10 anti-tumor drugs were evaluated by logistic analyses of the dose
      response curves. Distributions of Imax% appeared as normal curves, while those of
      the IC50 significantly deviated from normal distribution (p < 0.0001). We
      assessed the in vitro chemosensitivity by comparing the Imax % of each drug on
      individual samples with the mean Imax % + SD which was obtained from the Imax% of
      175 samples. If the individual Imax % > mean Imax % + SD. we thought the tumor
      sample was resistant to this drug. If the Imax % < or = mean Imax % + SD, we
      would compare its IC50 with Q50 which was used as a cutoff point for in vitro
      chemosensitivity of anti-tumor drugs. The in vitro chemosensitivity could be
      graded as sensitive (Q1-Q25), intermediate (Q26-Q75), and resistant (Q76-Q100) by
      means of percentile method. If the individual IC50 > or = Q76, the tumor sample
      would be defined as resistant. If the individual IC50 < or = Q25, it would be
      defined as sensitive. In the range of Q26-Q75, we used Q50 as a cutoff point
      between relative sensitivity and relative resistance. Preliminary results showed
      that the in vitro chemosensitivity to different anti-tumor drugs determined by
      these criteria were consistent with the clinical response in 83 advanced breast
      cancer patients.

PMID- 9776510
TI  - ErbB-2 protein in sera and tumors of breast cancer patients.
AB  - We compared levels of erbB-2 oncoprotein among three groups: Group I included 60
      asymptomatic women; Group II had 51 women with benign breast biopsies; and Group
      III had 67 women with node-negative breast cancer. Serological levels of erbB-2
      protein were measured in all participants; tumor levels were measured for Groups
      II and III. Forty-three percent of usable tumors (25/58), including three of
      seven lobular tumors, were erbB-2 positive. Tumor and blood oncoprotein levels
      were unrelated. Blood levels, however, were positively related to tumor volume,
      but only when the tumor had both a ductal carcinoma in situ (DCIS) component and
      an invasive component, suggesting a role for erbB-2 protein in progression of
      DCIS to invasive carcinoma. In Groups I and II serological levels of erbB-2
      protein were directly related to age, and inversely related to having had a live
      birth. Therefore, a model that determined the threshold levels of serological
      erbB-2 positivity in Group III included age and nulliparity as independent
      variables. Only three of the 67 women (4.5%) in Group III were positive for
      serological erbB-2. In a multivariate model, with serological erbB-2 as the
      dependent variable, and in which the independent variables included Study Group,
      there was a statistical trend for younger women, in which Group III had the
      highest serological levels of erbB-2, followed by Group II, and then Group I. In
      women who were over the age of 50 years the trend was reversed; i.e., levels of
      erbB-2 tended to be lowest in Group III, followed by Group II, and finally Group
      I.

PMID- 9776511
TI  - A principle of error compensation studied within a task of force production by a
      redundant set of fingers.
AB  - Based on previous studies, we formulated a principle of error compensation as a
      major principle of synergy organization during motor tasks performed by a
      redundant set of effectors. Within the present study, we tested the principle by
      an investigation of the performance of individual fingers during isometric force
      production when another task was performed simultaneously. Subjects were asked to
      press at about 30% of the maximal contraction force with three fingers (index,
      middle, and ring) acting in parallel. Then, they were required to perform a
      series of taps at 2 Hz with one of the fingers. In all the tasks, nontapping
      fingers changed their force production without a time delay with the changes in
      the force by the tapping finger. During tapping with the index and with the
      middle finger, both nontapping fingers showed changes in their force negatively
      correlated with changes in force of the tapping finger. During tapping with the
      ring finger, two types of behavior could be seen in different subjects with the
      force of the middle finger going out of phase (group 1) or in phase (group 2)
      with the force of the ring finger. In both cases, the force of the index finger
      was out of phase with the force of the ring finger. These changes, on average,
      induced a compensation for the expected drop in finger force during tapping,
      ranging in different conditions from 94% to 102%. The ratio of forces produced by
      the nontapping fingers did not change during the tapping in all the cases except
      group 2 during ring-finger tapping, when the index finger started to generate
      significantly higher force as compared to the middle finger. We interpret the
      data as results of the action of a feed-forward central mechanism leading to
      parallel changes in forces produced by fingers united into a structural unit.

PMID- 9776512
TI  - Processing of twitter-call fundamental frequencies in insula and auditory cortex
      of squirrel monkeys.
AB  - Amplitude-modulated (AM) and frequency-modulated (FM) elements are prominent
      periodic sound features of squirrel monkeys' twitter calls. To investigate how
      the periodic FM elements are represented in the spike activity of cortical
      neurons, single units in the insula, primary auditory field (AI) and rostral
      auditory field (R) were recorded. In five monkeys, 566 units (insula, n = 181;
      AI, n = 221; R, n = 164) were exposed to synthesized fundamental frequencies and
      one natural twitter call. Neuronal encoding of periodic FM elements takes place
      by phase-locking to either the up- or the down-directed FM sweeps. The phase
      locking was strongly influenced by the FM-period repetition rate. The ability of
      neurons in both auditory fields and the insula to encode all periodic FM elements
      showed a marked reduction at 16 Hz FM-period repetition rate. The neurons' best
      frequency (BF) influenced the quality of periodicity encoding, but neurons with
      BFs outside the frequency range of the fundamentals also responded with periodic
      discharge rates. Even neurons in AI (6.8%) and the insula (22.6%) that did not
      respond to pure tones showed clear periodic FM encoding. The percentage of
      neurons able to encode all periodic FM elements within the twitter fundamental
      was significantly higher in field R than in AI and the insula. From 58
      simultaneously recorded pairs of units in AI and the insula that had positive
      cross-correlation coefficients of spontaneous activity, the influence of the FM
      period repetition rate on neuronal correlation was investigated. Correlated
      firing of AI and insula neurons seems limited to low-period repetition rates. The
      cross-correlation coefficients obtained for spontaneous activity and six
      different periodic FM sounds showed a band-pass characteristic. The natural
      twitter call evoked stronger neuronal responses in all fields than the
      synthesized fundamental frequencies with corresponding bi-directional FM sweeps.
      The better encoding of the transient features in the natural call can be
      attributed to the amplitude modulation added to the FM elements in the natural
      call. These amplitude modulations divide the FM elements of twitter calls into
      syllable-like sound elements. It is probable that encoding the complex pattern in
      the time and frequency domains of a call must undergo some integration at a
      cortical level. Additionally, these data provide the first evidence that insula
      neurons contribute to the encoding of complex FM signals.

PMID- 9776513
TI  - Botzinger-complex expiratory neurons monosynaptically inhibit phrenic motoneurons
      in the decerebrate rat.
AB  - We examined respiratory neurons in the Botzinger complex of the medulla oblongata
      in 18 vagotomized, paralyzed, ventilated, and decerebrated rats and tested the
      hypothesis that bulbospinal expiratory neurons in this region monosynaptically
      inhibit phrenic motoneurons. First, we surveyed the types of respiratory neurons
      found in the Botzinger complex; only 11 of the 98 (approximately 11%) examined
      were bulbospinal, and all discharged only during late expiration (E2), usually
      with an augmenting discharge frequency (AUG). Then, we examined the spinal
      projections of 34 E2-AUG neurons using antidromic activation and found that all
      projected as far as the C4 or C5 segments of the spinal cord but no further
      caudally. Most (30, approximately 88%) had only unilateral projections, the
      majority (25, approximately 83%) ipsilateral, but 4 neurons (approximately 12%)
      had bilateral projections. Their axons could be antidromically activated at low
      currents (less than 10 microA) in the dorsal-lateral part of the spinal cord at
      the C2-3 border; 0.5-1.2 mm (mean+/-SD 0.84+/-0.23 mm) below the dorsal surface
      and 0.7-1.5 mm (1.19+/-0.25 mm) lateral from the midline. We sought evidence for
      connections from bulbospinal E2-AUG neurons to 118 phrenic motoneurons by
      computing spike-triggered averages (STAs) of their intracellular potentials
      triggered by the action potentials of 38 unilaterally-projecting E2-AUG neurons.
      Resting phrenic motoneuron membrane potentials ranged from -40 to -75 mV (-56+/-8
      mV) and fluctuations with the respiratory cycle from 7 to 20 mV (14+/-4 mV). Of
      the 118 STAs computed, hyperpolarizations were evident in 18 (approximately 15%)
      STAs, evoked by 11 of 38 (approximately 29%) E2-AUG neurons. Their amplitudes
      varied from 35 to 550 microV (105+/-113 microV), 10-90% fall times from 0.4 to
      0.9 ms (0.63+/-0.17 ms), and half-amplitude widths from 1.3 to 3.2 ms (2.0+/-0.52
      ms). Most (16/95, approximately 17%) of the STAs that displayed
      hyperpolarizations were associated with ipsilateral trigger neurons but some
      (2/23, approximately 9%) resulted from contralateral trigger neurons. We conclude
      that Botzinger-complex, expiratory neurons project to the C4 and/or C5 segments
      of the cervical spinal cord but no further caudal. Their axons are located
      dorsolaterally in the upper cervical segments of the spinal cord, and they
      monosynaptically inhibit phrenic motoneurons during the late part of expiration.

PMID- 9776514
TI  - Hand and joint paths during reaching movements with and without vision.
AB  - This study examines whether the kinematics of pointing movements are altered by
      the sensory systems used to select spatial targets and to guide movement. Hand
      and joint paths of visually guided reaching movements of human subjects were
      compared with two non-visual conditions where only proprioception was available:
      (1) movements of the same subjects with blindfolds, and (2) movements by
      congenitally blind subjects. While hand-path curvatures were overall quite small,
      sighted subjects wearing a blindfold showed a statistical increase in hand-path
      curvature compared with their visually guided movements. Blindfolded subjects
      also showed greater hand-path curvature than blind subjects. These increases in
      hand-path curvature for blindfolded subjects did not always lead to a decrease in
      joint-path curvature. While there were differences between blind subjects and
      sighted subjects using vision for some movement directions, there was no
      systematic difference between these two groups. The magnitude of joint-path
      curvature showed much greater variation than hand-path curvature across the
      movement directions. We found variation in joint-path curvature to be correlated
      to two factors, one spatial and one geometrical. For all subject groups, joint
      path curvature tended to be smaller for sagittal-plane movements than for
      transverse or diagonal movements. As well, we found that the magnitude of joint
      path curvature was also related to the relative motion at each joint. Joint-path
      curvature tended to increase when movements predominantly involved changes in
      shoulder angle and was minimal when movements predominantly involved elbow
      motion. The consistently small curvatures of hand trajectory across blind and
      sighted subjects emphasize the powerful tendency of the motor system to generate
      goal-directed reaching movements with relatively straight hand trajectories, even
      when deprived of visual feedback from very early in life.

PMID- 9776515
TI  - Cyclophosphamide cystitis as a model of visceral pain in rats: a c-fos and Krox
      24 study at telencephalic levels, with a note on pituitary adenylate cyclase
      activating polypeptide (PACAP).
AB  - This article is the fifth of a series aimed at mapping brain activities as they
      result from the development of cyclophosphamide (CP) cystitis in behaving rats
      using c-fos and Krox-24 expression. The inactive hepatic metabolites of CP are
      metabolized in the kidney to produce acrolein, which generates cystitis. Data
      come from animals which were injected once i.p. with either 1 ml saline (sham) or
      100 mg/kg CP in 1 ml saline under transient volatile anesthesia and which behaved
      freely for 1-4 h postinjection, 4 h being the minimum time for cystitis to
      completely develop. Survival times longer than 4 h were not studied owing to
      ethical considerations. The first 2 h postinjection cover a period of time over
      which inputs of multifactorial origin (stress and pain due to the intraperitoneal
      injection process, possible effects due to the presence of hepatic CP metabolites
      in blood, cystitis onset) interact in an indistinguishable way; the last 2 h are
      more cystitis specific as the other effects have vanished. Complete screening of
      telencephalic levels has been performed. These data complete previously published
      data at both spinal and subtelencephalic levels. Of all the telencephalic
      structures, only the bed nucleus of the stria terminalis in the dorsal part of
      its lateral division (BSTLd) and, to a lesser degree, the nucleus centralis of
      the amygdala, mostly in its caudal portion (cCeA), appeared to be significantly
      driven over the most specific cystitis period. Both of these structures had
      related, but not identical patterns of expression. They both reacted shortly
      after CP injection, but, while cCeA maintained its activity throughout cystitis
      development, BSTLd showed a rebound, reaching a peak value when cystitis was
      fully developed. Both of these areas are the only telencephalic areas to contain
      high PACAP38 immunoreactivity. This is evidence that, (1) both the BSTLd and cCeA
      could be the most rostral areas that visceronociceptive inflow would reach when
      cystitis genesis is under way, and (2) PACAP38 could be one of the neurochemical
      agents involved in telencephalic visceronociceptive processing. From our complete
      mapping of brain activities under a fully developed cystitis situation (4 h
      postinjection), it appears that the activities in BSTLd and cCeA are concomitant
      with those of both the dorsal vagal complex (DVC), paratrigeminal nucleus (PaT),
      and the ventrocaudal bulbar reticular formation (vcBRF) at brainstem levels,
      suggesting they all form the main part of the neural network that subserves the
      central processing of cystitis-related inputs, comprising pain and associated
      pseudoaffective responses. Both the DVC and BSTLd, which are the most powerfully
      driven areas, would be particularly important in such a way. The origin of these
      activities should be found in both vagal (as sensed through PaT activity) and
      spinal (pelvic) influences. This network profoundly differs from those reported
      for painful situations, either somatic or visceral, which controversally
      accompany positive cardiac inotropism.

PMID- 9776516
TI  - Effect of head position on postural orientation and equilibrium.
AB  - This study examined (1) how changes in head position affect postural orientation
      variables during stance and (2) whether changes in head position affect the rapid
      postural response to linear translation of the support surface in the horizontal
      plane. Cats were trained to stand quietly on a moveable platform and to maintain
      five different head positions: center, left, right, up, and down. For each head
      position, stance was perturbed by translating the support surface linearly in 16
      different directions in the horizontal plane. Postural equilibrium responses were
      quantified in terms of the ground reaction forces, kinematics, dynamics (net
      joint torques), body center of mass, and electromyographic (EMG) responses of
      selected limb and trunk muscles. A change in head position involved rotation of
      not only the neck but also the scapulae and anterior trunk. Tonic EMG levels were
      modulated in several forelimb and scapular muscles but not hindlimb muscles.
      Finally, large changes in head orientation in both horizontal and vertical planes
      did not hamper the ability of cats to maintain postural equilibrium during linear
      translation of the support surface. The trajectory of the body's center of mass
      was the same, regardless of head position. The main change was observed in joint
      torques at the forelimbs evoked by the perturbation. Evoked EMG responses of
      forelimb and scapular muscles were modulated in terms of magnitude but not
      spatial tuning. Hindlimb responses were unchanged. Thus, the spatial and temporal
      pattern of the automatic postural response was unchanged and only amplitudes of
      evoked activity were modulated by head position.

PMID- 9776517
TI  - Effect of altered sensory conditions on multivariate descriptors of human
      postural sway.
AB  - Multivariate descriptors of sway were used to test whether altered sensory
      conditions result not only in changes in amount of sway but also in postural
      coordination. Eigenvalues and directions of eigenvectors of the covariance of
      shnk and hip angles were used as a set of multivariate descriptors. These
      quantities were measured in 14 healthy adult subjects performing the Sensory
      Organization test, which disrupts visual and somatosensory information used for
      spatial orientation. Multivariate analysis of variance and discriminant analysis
      showed that resulting sway changes were at least bivariate in character, with
      visual and somatosensory conditions producing distinct changes in postural
      coordination. The most significant changes were found when somatosensory
      information was disrupted by sway-referencing of the support surface (P = 3.2 x
      10(-10)). The resulting covariance measurements showed that subjects not only
      swayed more but also used increased hip motion analogous to the hip strategy.
      Disruption of vision, by either closing the eyes or sway-referencing the visual
      surround, also resulted in altered sway (P = 1.7 x 10(-10)), with proportionately
      more motion of the center of mass than with platform sway-referencing. As shown
      by discriminant analysis, an optimal univariate measure could explain at most 90%
      of the behavior due to altered sensory conditions. The remaining 10%, while
      smaller, are highly significant changes in posture control that depend on sensory
      conditions. The results imply that normal postural coordination of the trunk and
      legs requires both somatosensory and visual information and that each sensory
      modality makes a unique contribution to posture control. Descending postural
      commands are multivariate in nature, and the motion at each joint is affected
      uniquely by input from multiple sensors.

PMID- 9776518
TI  - Opioid inhibition of rat medial vestibular nucleus neurones in vitro and its
      dependence on age.
AB  - Extracellular and whole-cell patch clamp intracellular recordings were made from
      rat medial vestibular nucleus (MVN) neurones in vitro, and their responses to
      selective mu-, kappa- and delta-opioid receptor agonists and antagonists were
      examined. Of 127 neurones tested, the large majority were inhibited in a dose
      dependent manner by the delta-opioid receptor agonists [D-Ala2, D-Leu5]
      enkephalin (DADLE) and [D-Pen2, Pen5]-enkephalin (DPLPE). The mu-opioid receptor
      agonist morphine and the kappa-receptor agonist U50,488 did not affect the tonic
      discharge rate of any of the 63 MVN cells tested. The delta-receptor antagonist
      naltrindole effectively antagonised the inhibitory effects of DADLE and DPLPE.
      Weak excitatory responses to high doses of DADLE were seen in only two MVN cells.
      These results demonstrate the presence of delta- but not mu- or kappa-opioid
      receptors on tonically active MVN neurones. Whole-cell intracellular recordings
      from MVN cells in a current clamp showed that the DADLE-induced inhibition was
      accompanied by membrane hyperpolarisation and decrease in input resistance, while
      voltage clamp experiments showed that DADLE induced an outward membrane current
      that was reduced but not abolished by 20 mM tetraethylammonium bromide. Thus the
      mechanisms of action of DADLE in inhibiting MVN cells involve the potentiation of
      outward K currents, in a similar way to the effects of opioids in other areas of
      brain. The inhibitory effects of DADLE increased linearly with age, so that the
      responses to DADLE in the youngest animals used here (60-80 g, approx. 3 weeks of
      age) were relatively small, increasing significantly over the following 2-3
      weeks. This age-dependence may be due to post-natal changes in the density of
      delta-opiate receptors or the efficacy of the signalling pathways activated by
      them in the MVN cells over this time.

PMID- 9776519
TI  - Visually evoked cortical potentials in awake cats during saccadic eye movements.
AB  - Visually evoked potentials (VEPs) measured under conditions of retinal image
      stabilization that minimized the influences of visual masking and smearing were
      averaged from electroencephalographic records measured from striate cortex of
      three cats. The amplitudes of the VEPs increased around saccade initiation. The
      grating-evoked potentials obtained at different times relative to the saccade
      exhibited changes in waveform shape that could be attributed to a saccade-evoked
      potential. The changes in the shape of the waveform were reasonably accounted for
      by the summation of the grating-evoked potential (produced when the cat did not
      make a saccade) and an appropriately timed saccade-evoked potential. The
      fundamental amplitudes of the residual potentials were computed and found to vary
      across the time course of the saccade. These observations suggest that there are
      other influences besides visual masking that are exerted early in the visual
      pathway to modulate visual processing during saccadic eye movements. A corollary
      discharge process is the most likely candidate to exert these influences.

PMID- 9776520
TI  - Neuronal responsiveness to three-dimensional motion in cat posteromedial lateral
      suprasylvian cortex.
AB  - The neuronal responsiveness to three-dimensional (3D) motion in cat posteromedial
      lateral suprasylvian (PMLS) cortex was studied using a computer-controlled,
      stereoscopic 3D graphic display capable of reproducing the major visual cues for
      natural 3D motion, including motion disparity, size, texture, and shading
      changes. The animals were anesthetized with nitrous oxide supplemented with
      alphaxalone, and paralysis prevented eye movement. Systematic investigation of
      neuronal responsiveness to 3D motions in 26 different directions revealed that
      more than half of the PMLS cells were selectively responsive to approaching (AP
      cells, 112 of 271) or recessive motion (RC cells, 64 of 271). The remaining cells
      were selectively responsive to frontoparallel motion (FP cells, 49 of 271) or
      nonselectively responsive to motion in multiple directions (NS cells, 46 of 271).
      The dependency on these visual cues was investigated as a reduction in the
      response amplitude or the response selectivity for the removal of a single cue
      from the motion stimuli containing the full visual cues. The AP and RC cells
      showed a strong dependency on the motion disparity cue, moderate dependency on
      the size cue, and weak dependency on the texture and shading cues. The FP cells
      showed no dependency on those visual cues. The cue dependency analysis indicated
      the existence of nonlinear interactions between those visual cues. Comparison of
      the responses to a combination of the motion disparity and size cues with the
      summed responses to each of the individual cues revealed that the responses to
      the combined cues are roughly predicted as a linear sum between the preferred
      responses. This comparison also showed nonlinear summation between the
      nonpreferred responses, i.e., responses to the combined cues were smaller than
      the summed responses. A similar quasilinear summation of the preferred responses
      between the two eyes and a nonlinear summation of the nonpreferred responses were
      found in the AP and RC cells for the motion disparity stimulus. All of these
      observations indicate that quasilinear and nonlinear interactions of the
      responses to various stimulus elements underlie the 3D motion responsiveness of
      the PMLS cells.

PMID- 9776521
TI  - Biphasic changes in F3/contactin expression in the gerbil hippocampus after
      transient ischemia.
AB  - We studied changes in expression of F3/contactin (F3), a neuron-specific adhesion
      molecule, in the gerbil hippocampus after transient forebrain ischemia for 5 min.
      By immunohistochemical techniques using F3 antibody, we found a biphasic change
      in immunoreactivity for F3 in the CA1 area after ischemia. Western blotting of F3
      protein showed a similar biphasic change. F3 immunoblots decreased to 67% of the
      control at 1 week, but then they increased and attained 159% at 3 weeks and 152%
      at 5 weeks after ischemia. Immunoreactivity of a neurofilament (NF145) showed a
      similar biphasic change to F3 but to a lesser extent. In contrast, microtubule
      associated protein 2 (MAP2) immunoreactivity uniformly decreased after ischemia.
      In situ hybridization revealed that F3 messenger RNA (mRNA) hybridization signals
      in CA1 area were greatly reduced 1 week after ischemia, while the signals in the
      CA3 area were unchanged and even increased 3 weeks after ischemia. Damage to CA3
      neurons by hyperthermic ischemia blocked the F3 increase in area CA1. Our results
      suggest that the initial decrease in F3 following ischemia reflects loss of CA1
      neurons and the late increase in F3, which shows that a similar time course with
      neurofilaments may be caused by neurite sprouting.

PMID- 9776522
TI  - Gaze stabilization during dynamic posturography in normal and vestibulopathic
      humans.
AB  - Dynamic posturography by measurement of center of pressure (COP) is a widely
      employed technique for evaluating the vestibular system. However, the
      relationship of COP motion to vestibulo-ocular reflex (VOR) function and image
      stability on the retina has not been determined previously. To assess these
      relationships, we report gaze, head, and trunk stability during dynamic
      posturography in 11 normal volunteers, 7 subjects with unilateral vestibular
      lesions, and 3 subjects with bilateral vestibular lesions. Posturographic tasks
      consisted of standing still and standing on a platform that was sliding (0.2 Hz),
      tilting (0.1 Hz), or covered with a foam cushion 6 cm thick while tilting (0.1
      Hz). Each perturbation was imposed in the anterior-posterior and repeated in the
      medial-lateral direction, in both light and darkness. Subjects viewed (or in
      darkness remembered) a target located 50, 100, or 500 cm distant. COP, angular
      eye position, and angular and linear orbit and trunk positions were measured
      using magnetic search coils and flux gate magnetometer sensors. With the target
      visible, the velocity of image motion on the retina was on average always less
      than 1 degree/s, well within the range consistent with high visual acuity. In
      darkness, gaze velocity increased for normal and vestibulopathic subjects. During
      tilt, vestibulopathic subjects had a significantly greater gaze velocity than
      controls. Gain of the angular VOR (eye velocity/head velocity) was significantly
      lower in darkness than in light and in vestibulopathic as compared to control
      subjects. Gain of the VOR was significantly correlated with gaze instability, but
      variation in VOR gain accounted for only 20-40% of the variance. In darkness, the
      velocity of the COP was significantly greater in vestibulopathic than control
      subjects for every condition tested. In light, this difference was small and
      often not significant. Although spectral analysis of the COP indicated
      frequencies above 1 Hz that were not observed in motion of the trunk and orbit,
      root mean square (RMS) velocities of the trunk and orbit in the horizontal plane
      were higher in darkness and in vestibulopathic subjects, mirroring COP findings.
      Only in vestibulopathic subjects tested in darkness was there a correlation
      between COP velocity and gaze velocity; COP velocity was otherwise uncorrelated
      with gaze. Gaze velocity was greater with near than with distant targets.
      Vertical VOR gain was higher with near targets. No other significant effects of
      target distance were found. Head movement strategy, VOR gain, and COP were all
      unaffected by target proximity. These data show that gaze velocity measurements
      during dynamic posturography in darkness are sensitive to vestibular loss. With a
      visible target, both COP and gaze stability of vestibulopathic subjects are
      difficult to distinguish from normal. During visual feedback, it is likely that
      image stabilization over the range of frequencies tested is achieved through
      better head stability and through visual tracking, allowing vestibulopathic
      subjects to maintain adequate visual acuity.

PMID- 9776523
TI  - Spatial disparity affects visual-auditory interactions in human sensorimotor
      processing.
AB  - Information from the auditory and visual systems converges in the nervous system
      with physiological and behavioral consequences. Most of our knowledge about the
      rules governing such convergence has been obtained in experiments where the
      strength or the timing of the individual auditory and visual stimuli has been
      varied. Relatively little attention has been paid to the spatial relationship
      between different modalities of stimuli in multisensory experiments. We studied
      saccadic reaction times of human subjects to bimodal auditory and visual stimulus
      presentations under two conditions: first, with the targets spatially coincident
      and, second, with various degrees of spatial separation or disparity. In the
      first experiment, we found that the saccadic reaction times were consistently
      shorter than would be predicted by independent processing of information about
      the visual and auditory targets. These results suggest convergence of multimodal
      information at one or more loci within the nervous system. In the second
      experiment, we found that saccadic latency gradually increased as spatial
      distance between the auditory and visual targets increased. Evidence for neural
      summation was found over a wide range of spatial disparities. These results
      suggest that multisensory information can be integrated and have significant
      influences on behavior over a surprisingly large range of spatial disparity.

PMID- 9776524
TI  - Use and misuse of albumin infusions in neonatal care.
AB  - During the neonatal period, albumin infusions are administered in response to a
      variety of clinical scenarios. Review of currently available literature, however,
      demonstrates that crystalloid rather than colloid infusions should be used both
      to treat hypovolaemic hypotension and as the replacement fluid in a dilutional
      exchange. The role of an albumin infusion in "treating" metabolic acidosis needs
      further evaluation, but the practice of giving albumin to correct "asymptomatic"
      hypoalbuminaemia or at resuscitation should be discouraged. CONCLUSION: The
      neonatologist would be well advised, when reaching for an albumin infusion, to
      reflect that there may be a safer, certainly cheaper and equally effective
      alternative.

PMID- 9776525
TI  - Growth hormone secretion, puberty and adult height after cranial irradiation with
      18 Gy for leukaemia.
AB  - The dose of prophylactic cranial irradiation given to patients for acute
      lymphoblastic leukaemia has been decreased from 24 to 18 Gy, but the beneficial
      effect of this decrease on growth is controversial. This study compares the
      growth hormone (GH) secretion and growth of 35 patients (20 boys) given 18 Gy at
      3.7+/-0.3 (SE) years, and routinely evaluated 5.4+/-0.4 years after irradiation
      to define the indications for GH treatment in these patients. Of these, 63% had a
      low GH peak (< 10 microg/l) after one (22 cases) or two (17 cases) stimulation
      tests. The plasma concentrations of insulin-like growth factor I and its GH
      dependent binding protein were normal for age in all but two cases. The height
      changes between irradiation and evaluation were correlated with the GH peaks (P <
      0.03) and were concordant, except in patients with early puberty. This occurred
      in 16 patients including all 12 girls irradiated before 4 years of age. A
      significant (P < 0.03) reduction in height (SD) between irradiation and adult
      height occurred in untreated GH-deficient patients (-1+/-0.3, n=6), but not in GH
      deficient patients given GH (-0.6+/-0.3, n=8) or in those with normal GH peak (
      0.4+/-0.3, n=7). CONCLUSION: In children irradiated for acute lymphoblastic
      leukaemia, GH deficiency is frequent after 18 Gy but its impact on adult height
      is smaller than after higher doses. We suggest that the indications for
      gonadotropin releasing hormone analogue therapy should be broad in patients with
      early or rapidly progressing puberty and those for GH therapy in those patients
      with a below average constitutional height before irradiation.

PMID- 9776526
TI  - Prepubertal girls with insulin-dependent diabetes mellitus have higher exogenous
      insulin requirement than boys. Childhood Diabetes in Finland Study Group.
AB  - In a population based study, the prescribed insulin dose of 348 prepubertal
      children with insulin-dependent diabetes mellitus (IDDM) was analysed 2 years
      after the diagnosis of diabetes. Girls had an insulin dose 13.6% higher than that
      in boys. When children younger than 5 years of age at diagnosis were analysed
      separately, the difference in insulin dose between boys and girls remained. The
      increased insulin dose in girls was not explained by possible differences in
      endogenous insulin secretion, body mass index, metabolic control or the number of
      daily insulin injections. Our observations indicate that prepubertal girls with
      IDDM have a poorer insulin sensitivity than boys.

PMID- 9776527
TI  - Good growth despite very low levels of insulin-like growth factors.
AB  - A 12.5-year-old girl presented with short stature. Insulin-like growth factor
      1(IGF-I) and insulin- like growth factor binding protein (IGFBP-3) were below the
      0.1 percentile. Growth hormone provocation tests disclosed normal responses to L
      arginine and insulin-induced hypoglycaemia. A huge benign mesenteric cyst was
      discovered by abdominal ultrasound and completely removed. Subsequently, the girl
      showed a marked catch-up growth; however, IGF-I and IGFBP-3 remained below the
      0.1 percentile. CONCLUSION: These observations imply that growth may take place
      even with very low levels of insulin-like growth factors. The interpretation of
      low IGF-I and IGFBP-3 levels in short children still requires good clinical
      judgement and basic knowledge of their biological action.

PMID- 9776528
TI  - Idiopathic non-obstructive hypertrophic cardiomyopathy, vitamin B12 deficiency
      and gastric adenocarcinoma: an unreported association in a teenager.
AB  - A 14-year-old boy presented with anorexia and weakness whereon the diagnosis of
      dimorphic anaemia was made. An excellent response to iron and vitamin B12 was
      observed. In addition, the patient had non-obstructive hypertrophic
      cardiomyopathy. At endoscopy 2.5 years later, an adenocarcinoma was diagnosed and
      the patient underwent a high subtotal gastrectomy. To the best of our knowledge,
      this rare association has never been reported in children. CONCLUSION: We report
      a youngster with pernicious anaemia, associated with nonobstructive hypertrophic
      cardiomyopathy in whom gastric adenocarcinoma was found. Patients with pernicious
      anaemia are at greater risk of developing gastric carcinoma than the general
      population, therefore we recommend routine periodic gastroscopic surveillance in
      the paediatric population with pernicious anaemia.

PMID- 9776529
TI  - Long-term somatic and mental development of children after periconceptional
      multivitamin supplementation.
AB  - The preventive effect of periconceptional folic acid-containing multivitamin
      supplementation compared to placebo-like trace element tablets on the number of
      first-occurring neural-tube defects was well documented in the Hungarian
      randomized double-blind trial. The effect of this new primary prevention on the
      early (first 11 months) postnatal development has also been studied. This follow
      up was expanded to children at the 2nd and 6th years of age studied previously by
      a blind examination of their somatic and mental development. Confounding factors
      and case histories were evaluated and paediatric, ophthalmological, audiological
      and psychometric examinations were performed on 625 children. CONCLUSION: There
      were no differences in the rate and distribution of disorders including allergies
      (except otitis media), ophthalmological and audiological anomalies,
      anthropometric and mental development between children who belonged to the
      multivitamin or to the trace element group.

PMID- 9776530
TI  - Neurodevelopmental outcome after prenatal exposure to opiates.
AB  - To study the developmental effects of prenatal exposure to opiates, a prospective
      follow up study of 34 drug-exposed (opiates and nicotine) and 42 reference
      infants (nicotine exposure only) was conducted from January 1992 to September
      1995. At the time of delivery, 12 of 34 mothers used opiates without medical
      control. Twenty-two mothers participated in a methadone maintenance programme. At
      1 year, the average Griffiths Developmental Quotient (DQ) was lower in the drug
      exposed group (mean: 100.5 vs. references 107.9; P < 0.001). This difference was
      mainly due to lower subscales "locomotor" (mean 100.8 vs. 111.4; P < 0.05) and
      "intellectual performance" (mean 100.8 vs. 108.5; P < 0.05) in the drug-exposed
      group. Severe developmental retardation mean DQ (-2 SD) was diagnosed in 2 drug
      exposed infants. Mild developmental retardation (mean DQ: 1 SD- > 2 SD) was found
      in 7 drug-exposed and in 3 reference infants (P < 0.05). Neurological
      abnormalities were found more frequently in the drug-exposed group (11 vs. 3
      infants; P < 0.01). Among the opiate-exposed infants, the subscales "hearing and
      speech" and "intellectual performance" were lower in the uncontrolled drug-using
      than in the methadone group. The 17 fostered infants showed no difference in
      developmental outcome compared with the 10 infants living with their biological
      parents (mean DQ: 100.0 versus 101.3). CONCLUSIONS: At 1 year infants prenatally
      exposed to opiates are at risk for mild psychomotor developmental impairment.

PMID- 9776531
TI  - Middle ear effusion among children diagnosed and treated actively for acute
      otitis media.
AB  - We assessed the point prevalence of middle ear effusion among day care children
      in an area where acute otitis media is diagnosed, treated and followed actively.
      Minitympanometry was used to screen 850 day care centre attendants aged 0.6 to
      6.9 years (mean 3.7 years). Tympanometry was performed by two trained nurses at
      the day care centres and pneumatic otoscopy was done by a paediatrician when
      effusion was suspected. We found 60 (7.1%) children to have middle ear effusion,
      which was bilateral in 23 (2.7%) cases. Of the children with bilateral effusion
      13 had respiratory symptoms fulfilling the criteria of acute otitis media, 8 of
      them had experienced acute otitis media during the past 3 weeks and were
      diagnosed to have otitis media with effusion, and only 2 (0.2%) were asymptomatic
      children not identified earlier. Of the 37 (4.4%) children with unilateral
      effusion, 14 had acute otitis media and 23 otitis media with effusion, of whom 12
      children (1.4%) had not been identified earlier. The point prevalence of acute
      otitis media was 3.2% and that of otitis media with effusion 3.9%. CONCLUSION: We
      conclude that active diagnosis and treatment of acute otitis media practically
      eliminates such middle ear effusion that could cause significant hearing
      impairment.

PMID- 9776532
TI  - Necrotizing toxoplasmic encephalitis in a child with the X-linked hyper-IgM
      syndrome.
AB  - We report on a 9-year-old boy with the hyper-IgM syndrome who presented with
      rapid impairment of consciousness. The brain CT scan showed multiple round
      lucencies, and the brain histology revealed necrotizing toxoplasmic encephalitis.
      This patient, whose CD40/CD40 ligand system was impaired, indicates the
      importance of this system for defence against toxoplasmic infection. CONCLUSION:
      Although disseminated toxoplasmosis is a rare complication of the hyper-IgM
      syndrome, it must be included in the differential diagnosis of infections.

PMID- 9776534
TI  - Stroke-like encephalopathy in an infant with 3-hydroxy-3-methylglutaryl-coenzyme
      A lyase deficiency.
AB  - A 2.5-year-old boy presented with acute metabolic decompensation in whom 3
      hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) lyase deficiency was diagnosed.
      Four days after metabolic decompensation, a stroke-like encephalopathy with tonic
      clonic convulsion of the left arm and leg and coma developed. Brain oedema and
      subsequent demarcation and atrophy were observed mainly within the supply areas
      of the right anterior and middle cerebral artery and to a lesser extent in
      various sites within the right hemisphere. Residual neurological deficits
      included spastic paresis of the left arm and leg. and left supranuclear facial
      palsy and aphasia, indicating bilateral diffuse brain affection. CONCLUSION: In
      the presented patient with HMG-CoA lyase deficiency, stroke-like encephalopathy
      occurred days after metabolic decompensation indicating ongoing (intracerebral)
      metabolic derangement. Monitoring of the intracerebral accumulation of toxic
      metabolites by magnetic resonance spectroscopy and of cerebral haemodynamics
      might be useful for a better understanding of the pathogenetic mechanisms of
      stroke-like encephalopathy and to identify patients at risk.

PMID- 9776533
TI  - Slowly deteriorating insulin secretion and C-peptide production characterizes
      diabetes mellitus in infantile cystinosis.
AB  - Infantile cystinosis, a rare lysosomal storage disease of cystine, leads to
      Fanconi syndrome and end-stage renal failure. After renal transplantation, no
      recurrence of the disease occurs in the graft, but other organ involvement
      becomes evident later in life. Diabetes mellitus has been associated with
      cystinosis, but the mechanisms of impaired glucose tolerance have not yet been
      characterized. Here, we studied glucose tolerance, glucose constant decay (k
      values), insulin and C-peptide by intravenous glucose tolerance test (IVGTT) in
      eight patients with infantile cystinosis (three with impaired GFR (CRF) and five
      after kidney transplantation (KTX)). For comparison, 15 age-matched children with
      CRF and 15 age-matched KTX patients were analysed. Both early and second insulin
      secretion phases were diminished in patients with infantile cystinosis, whereas
      in CRF, k-values were no different from control patients. After renal
      transplantation, k-values were significantly lower in cystinotic patients with a
      markedly reduced early insulin secretion phase. There was a significant negative
      correlation between k-values and age in patients with cystinosis. Repetitive
      IVGTTs in these patients demonstrated progressive but rather slow loss of first
      phase insulin secretion and C-peptide production, suggesting a slowly reducing
      secretion potential of the beta cell due to cystine storage. CONCLUSION: Unlike
      type I diabetes mellitus, glucose intolerance in patients with infantile
      cystinosis is characterized by a slow, progressive loss of insulin secretion and
      C-peptide production. For these patients, the data indicate a 50% risk of
      developing glucose intolerance by the age of 18 years. We recommend to perform
      intravenous glucose tolerance tests at 5-year intervals.

PMID- 9776535
TI  - Disease-related response to inhaled nitric oxide in newborns with severe
      hypoxaemic respiratory failure. French Paediatric Study Group of Inhaled NO.
AB  - Inhaled nitric oxide (iNO) has been shown to improve oxygenation in severe
      persistent pulmonary hypertension of the newborn (PPHN). However, PPHN is often
      associated with various lung diseases. Thus, response to iNO may depend upon the
      aetiology of neonatal acute respiratory failure. A total of 150 (29 preterm and
      121 term) newborns with PPHN were prospectively enrolled on the basis of
      oxygenation index (OI) higher than 30 and 40, respectively. NO dosage was
      stepwise increased (10-80 ppm) during conventional mechanical or high-frequency
      oscillatory ventilation while monitoring the oxygenation. Effective dosages
      ranged from 5 to 20 ppm in the responders, whereas iNO levels were unsuccessfully
      increased up to 80 ppm in the nonresponders. Within 30 min of iNO therapy, OI was
      significantly reduced in either preterm neonates (51+/-21 vs 23+/-17, P < .0001)
      or term infants with idiopathic or acute respiratory distress syndrome (45+/-20
      vs 20+/-17, P < .0001), 'idiopathic' PPHN (39+/-14 vs 14+/-9, P < .0001), and
      sepsis (55+/-25 vs 26+/-20, P < .0001) provided there was no associated
      refractory shock. Improvement in oxygenation was less significant and sustained
      (OI=41+/-16 vs 28+/-18, P < .001) in term neonates with meconium aspiration
      syndrome and much less (OI=58+/-25 vs 46+/-32, P < .01) in those with congenital
      diaphragmatic hernia. Only 21 of the 129 term newborns (16%) required
      extracorporeal membrane oxygenation (57% survival). Survival was significantly
      associated with the magnitude in the reduction in OI at 30 min of iNO therapy, a
      gestational age > or =34 weeks, and associated diagnosis other than congenital
      diaphragmatic hernia. Conclusion, iNO improves the oxygenation in most newborns
      with severe hypoxaemic respiratory failure including preterm neonates. However,
      response to iNO is disease-specific. Furthermore, iNO when combined with adequate
      alveolar recruitment and limited barotrauma using exogenous surfactant and HFOV
      may obviate the need for extracorporeal membrane oxygenation in many term
      infants.

PMID- 9776536
TI  - Five-year study of medical or surgical treatment in children with severe vesico
      ureteral reflux dimercaptosuccinic acid findings. International Reflux Study
      Group in Europe.
AB  - The results of serial dimercaptosuccinic acid (DMSA) imaging over 5 years are
      reported in 287 children with severe vesico-ureteral reflux entered into the
      European Branch of the International Reflux Study in Children. The children were
      randomly allocated to medical (n=147) or surgical (n=140) management and DMSA
      studies were performed during the follow up period at least 6 months after any
      urinary tract infection. Abnormal images were classified into four types: (1)
      large polar hypodensity with normal renal outline; (2) peripheral photon
      deficient defect(s) in a non-deformed kidney; (3) small renal image with normal
      contour; and (4) peripheral defect(s) with resultant irregularity of the renal
      outline. The DMSA findings were abnormal at entry in 235 (82%) with no difference
      in incidence or severity between the two treatment groups. During follow up,
      deterioration was observed in 25 medically and 23 surgically treated patients and
      comprised image deterioration alone in 17, image deterioration with corresponding
      reduction in differential function in 16 and reduction in relative function
      without image change in 15, with similar distribution between the two treatment
      groups. Deterioration was more frequent in children entering the study under the
      age of 2 years and in those with grade IV rather than grade III reflux. These
      findings, showing no difference in outcome between children managed surgically or
      medically, are consistent with the radiological results already published.
      CONCLUSION: In the International Reflux Study the DMSA scintigraphic data showed
      no difference in outcome between children managed surgically or medically.

PMID- 9776537
TI  - Chronic renal failure in infants: effect of strict conservative treatment on
      growth.
AB  - Twenty infants with chronic renal failure from the first weeks of life, received
      strict conservative treatment consisting of a protein-restricted, calorie
      enriched diet, supplements of essential amino acids, sodium chloride, sodium
      bicarbonate, calcium and vitamin D. The last 10 patients also received
      erythropoietin. Neither nasogastric nor gastrostomy tubes were used in any of
      these patients. Four patients needed dialysis in the second half of the 1st year
      of life. We analysed the patients' growth in weight, height and head
      circumference from birth until the age of 12 months. At the age of 12 months,
      mean values of height, weight and head circumference SDS were -1.63, -1.53 and 
      1.01 respectively as compared to healthy children. The body length data also
      compare favourably with those from a large cohort of chronic renal failure
      patients collected by the European Study Group for Nutritional Treatment of
      Chronic Renal Failure in Childhood; here the mean height SDS at 12 months of age
      is -3.3. CONCLUSION: This retrospective analysis shows that the generally
      observed progressive growth retardation in infants with chronic renal failure can
      be prevented by early and adequate conservative management.

PMID- 9776538
TI  - Fatty acid composition of lipid classes in maternal and cord plasma at birth.
AB  - The fatty acid composition of plasma phospholipids, triglycerides, cholesterol
      esters and nonesterified fatty acids was determined by high-resolution capillary
      gas-liquid chromatography in 41 pairs of mothers and their term infants at time
      of birth. The total free fatty acid content in maternal and cord plasma was
      positively correlated, possibly reflecting a passive, gradient dependent
      transplacental passage of nonesterified fatty acids. Higher percentage values of
      several saturated and monounsaturated fatty acids in cord than in maternal plasma
      phospholipids, triglycerides and nonesterified fatty acids may have resulted from
      an active fetal fatty acid synthesis. Trans fatty acids were found in every lipid
      class at similar or slightly lower percentages in neonatal as in maternal plasma,
      thus confirming their placental passage. Long-chain n-6 and n-3 polyunsaturated
      fatty acids are preferentially incorporated into phospholipids and sterolesters
      of both maternal and cord plasma. Linoleic and alpha-linolenic acids were found
      in smaller portions in cord than in maternal fatty acids, in contrast to
      strikingly higher proportions of their long-chain polyunsaturated metabolites,
      which may indicate a discriminating placental transport for certain
      physiologically important long-chain polyunsaturated fatty acids. CONCLUSION: The
      fetus appears to obtain fatty acids from a combination of de novo synthesis, a
      passive gradient dependent transplacental passage of nonesterified fatty acids
      and a selective materno-fetal placental transport for certain fatty acids, such
      as physiologically important long-chain polyunsaturated fatty acids.

PMID- 9776539
TI  - Medication errors in paediatric practice: insights from a continuous quality
      improvement approach.
AB  - The objective was to assess the incidence and consequences of medication errors,
      highlight sources of recurrent error and institute changes in practice to prevent
      their recurrence. Utilising a continuous quality improvement approach, a 2-year
      prospective cohort study was undertaken using an adverse incident reporting
      scheme. A multidisciplinary committee analysed medication error reports,
      classifying them according to type (prescription, supply or administration),
      severity (serious or not serious) and clinical outcome. Changes in policy and
      practice were implemented to reduce the frequency of errors. There were 441
      reported medication errors in the study period, during which 682 patients were
      admitted for 5315 inpatient days. Errors were more seven times likely to occur in
      the intensive care setting. Doctors accounted for 72% of errors and prescription
      errors doubled when new doctors joined the rotation. Most errors (68%) were
      detected prior to drug administration. Twenty-four serious medication errors were
      not detected in advance, but only 4 had overt clinical consequences. Excluding
      prevented errors and appropriate deviations from prescribed therapy, there were
      117 actual medication errors (1/5.8 admissions, or 1/45 inpatient days). During
      the 2nd year of the scheme, the incidence of all reported errors, administration
      errors and serious errors fell, but the prescription error rate remained
      constant. CONCLUSIONS: Medication errors occurred commonly in this study, but
      adverse consequences were rare. The non-punitive, multidisciplinary approach to
      medication errors utilised in this study increased staff vigilance, highlighted
      sources of recurrent error, and led to changes in drug policies and staff
      training, which resulted in improved patient safety and quality of care.

PMID- 9776540
TI  - A toddler with persistent vomiting and diarrhoea.

PMID- 9776541
TI  - Clinical importance of essential fatty acid deficiency.

PMID- 9776542
TI  - Ethosuximide-associated lupus with cerebral and renal manifestations.

PMID- 9776544
TI  - Frequency of the HIV-1 resistance CCR5 deletion allele in Hungarian newborns.

PMID- 9776543
TI  - Unexpectedly prolonged colonization of exfoliative toxin A-producing methicillin
      resistant Staphylococcus aureus in infants.

PMID- 9776545
TI  - Chemoreflex thresholds to CO2 in decerebrate cats.
AB  - We used a modified rebreathing technique to measure chemoreflex thresholds to CO2
      in decerebrate, paralyzed and ventilated cats. Cats were hyperventilated to
      neural apnea (PaCO2 < 15 mmHg) with one ventilator and then switched to a
      rebreathing circuit consisting of a balloon inside a bottle connected to a second
      ventilator. The volume of the circuit was approximately 110 ml. The balloon
      contained 5% CO2:95% O2 for hyperoxic rebreathing or approximately 5% CO2 with 11
      or 6.5% O2 for moderately and severely hypoxic rebreathing. A plateau in CO2
      concentration at the onset of rebreathing indicated equilibration of CO2 between
      the circuit, alveolar gas and venous and arterial blood. After rapid
      equilibration of CO2 between the cat and the circuit, CO2 increased linearly with
      time during rebreathing. Under hyperoxic conditions, phrenic activity began to
      increase at an end-tidal P(CO2) (PET(CO2)) of 35.1 +/- 6.1 (SD) mmHg (n = 8);
      during hypoxia, phrenic activity began to increase at a significantly lower
      PET(CO2) of 27.8 +/- 4.8 mmHg (P < 0.01, n = 6). We interpret these values as the
      central and peripheral chemoreflex thresholds to CO2, respectively. Persistent
      phrenic activity prevented determination of a threshold during severe hypoxic
      rebreathing. Our modified method of hyperoxic and hypoxic rebreathing allows
      detection of the effects of hypoxia on the central and peripheral chemoreflex
      thresholds and, within a cat, measurements of chemoreflex sensitivities.

PMID- 9776547
TI  - Effect of cardiac output on pulmonary gas exchange: role of diffusion limitation
      with VA/Q mismatch.
AB  - We studied the effect of the interaction between diffusion limitation and
      alveolar ventilation to perfusion ratio (VA/Q) mismatch in the relation between
      blood gas partial pressures and cardiac output (Q). The analysis was based on a
      mathematical model of gas exchange involving two exchanging compartments and a
      right to left shunt. A system of equations describing alveolar-arterial mass
      conservation for O2, CO2 and N2 and Bohr integration for O2 and CO2 was
      interactively solved to find sets of alveolar and blood gas partial pressures
      fitting input data. Simulations used values compatible with patients in
      respiratory failure and neonate piglets. Association of (VA/Q) mismatch and
      diffusion impairment limited the increase of PaO2 with Q. A maximum in the PaO2
      vs. Q curve can be attained, further Q increases lead to reductions in PaO2. The
      effect was accentuated by increasing (VA/Q) and diffusion to perfusion
      heterogeneity. Combination of (VA/Q) mismatch and diffusion limitation was
      synergistic leading to greater reductions in PaO2 than expected from simple
      addition of their independent influences. The findings are compatible with
      experimental data.

PMID- 9776546
TI  - Cardiorespiratory responses to glutamate microinjected into the medullary raphe.
AB  - The involvement of the medullary raphe in modulating cardiorespiratory activity
      was examined by microinjecting L-glutamate (L-Glu) into the raphe of rats.
      Animals were vagotomized, paralyzed, artificially ventilated, maintained at 37
      degrees C, and instrumented to record arterial blood pressure (BP) and phrenic
      nerve activity (PNA). Mock cerebrospinal fluid (mCSF, 10 nl, pH 7.4; control) and
      L-Glu dissolved in mCSF (10, 100, 1000 mM; 10 nl; pH 7.4; experimental) were
      microinjected into the raphe. L-Glu affected both BP and PNA in a dose dependent
      manner. Blood pressure was reduced by 6.30 +/- 0.97 and 12.98 +/- 1.29% by 100
      and 1000 mM L-Glu, respectively, without affecting heart rate. PNA increased by
      23 and 38% with 100 and 1000 mM L-Glu, respectively. Mock CSF and 10 mM L-Glu had
      no effect. It is concluded that there are sites in the medullary raphe that
      affect blood pressure only and other sites which can affect both blood pressure
      and respiration.

PMID- 9776548
TI  - A significant proportion of exhaled nitric oxide arises in large airways in
      normal subjects.
AB  - Nitric oxide (NO) of endogenous origin is present in exhaled breath. An increase
      in exhaled NO concentration (ENO) has been described in bronchial asthma and ENO
      falls after inhaled steroid therapy. The sources of ENO may include pulmonary
      blood, the gas exchange region, conducting airways and the nasal cavity. In four
      healthy volunteers, a catheter was placed in a main bronchus after topical
      anesthesia in order to sample airway NO (CNO). Exhaled nitric oxide of
      bronchopulmonary and oropharyngeal origin (ENO(b/o)) was measured while excluding
      nasal NO and was controlled for expiratory flow. During the same exhalation,
      ENO(b/o) was compared to CNO at multiple sites in the airway as the catheter was
      progressively withdrawn. Mean CNO concentration in a position corresponding to a
      main bronchus was 51.4 +/- 10.8% of ENO(b/o). As the catheter was withdrawn, mean
      CNO concentration progressively increased both in absolute values and as a
      proportion of ENO(b/o), until in the oropharynx, it was 96.1 +/- 5.2% ENO(b/o).
      We conclude that a significant proportion of ENO(b/o) arises in the large airways
      and trachea in normal subjects and contains a minor oropharyngeal component.

PMID- 9776549
TI  - The effect of NO synthase inhibition on blood oxygen-carrying function during
      hyperthermia in rats.
AB  - Hyperthermia is known to be accompanied by considerable worsening of body oxygen
      delivery. Nitric oxide (NO) is a messenger that contributes to the regulation of
      oxygen transport (vasodilation, formation of nitrosohemoglobin, erythrocyte
      deformability), but also has cytotoxic effects (when abundantly generated by
      inducible NO synthase and through a formation of peroxynitrite). The effects of
      NO synthesis inhibition on the blood oxygen transport (hemoglobin-oxygen affinity
      and erythrocyte deformability) were investigated in rats with hyperthermia. The
      most considerable changes in blood oxygen transport indices and the most
      pronounced hypoxia were observed in rats that received the NO synthase inhibitor
      N(omega)-nitro-L-arginine methyl ester (L-NAME) i.p. Its administration before
      heating significantly impaired body oxygen delivery, with a shift of the
      oxyhemoglobin dissociation curves rightwards and lowering of erythrocyte
      deformability. The changes in the blood oxygen transport in animals receiving L
      arginine and L-NAME to prevent NO synthase inhibition were similar to those in
      rats treated with isotonic NaCl before heating.

PMID- 9776550
TI  - Pulmonary blood flow measured by inspiratory inert gas concentration forcing
      oscillations.
AB  - The aim of this study was to discover if the forced inspired inert gas sinewave
      technique could be used to measure pulmonary blood flow, using nitrous oxide as
      the indicator gas, following inotropic stimulation of the heart by dobutamine, in
      the presence of a constant alveolar ventilation. Cardiac output (range 1-4.5 L
      min(-1)) was measured in six dogs by thermodilution and by calculation from the
      sinusoidal expired partial pressures of argon and nitrous oxide using: (i)
      analytical equations and a conventional continuous ventilation three-compartment
      lung model, which did not include recirculation; and (ii) a digital simulation
      tidal ventilation lung model (Gavaghan and Hahn, 1996. Respir. Physiol. 106, 209
      221) which was adapted to include nitrous oxide mixed-venous recirculation from a
      combined single viscera compartment. The continuous ventilation model
      calculations always underestimated thermodilution cardiac output, with the bias
      error increasing to almost -1 L min(-1) at the longest forcing periods, 4-5 min.
      In contrast, the tidal ventilation model calculations were in close agreement to
      thermodilution cardiac output, with biases of -0.04 and -0.26 L min(-1) at
      forcing periods of 2 and 3 min, respectively.

PMID- 9776551
TI  - Normoxic ventilatory response in lowlander and Sherpa elite climbers.
AB  - The differences in ventilatory response to exercise of some highland ethnic
      communities is a controversial issue. We have evaluated the differences in
      ventilatory response to exercise at sea level between two groups of elite
      climbers, four Himalayan Sherpas (S) and four Caucasian lowlanders (C), after
      descent from extreme altitude. All of them performed a progressive-intensity
      exercise test on a treadmill under normoxic conditions. Pulmonary gas exchange
      was obtained until exhaustion by means of an automatic gas-analyzer system.
      Significant differences in expired ventilation and carbon dioxide production were
      found between the two groups, the VE x VO2(-1) being lower in the S at rest (41.9
      +/- 5) in comparison with C (48.7 +/- 9) (P < 0.05), higher at medium loads of
      the test (S = 28.2 +/- 4 vs. C = 25.7 +/- 2; P < 0.05) and reaching similar
      values at higher loads (S = 34.5 + 2 vs. C = 35.6 +/- 4; NS). We conclude that
      the special ventilatory response observed in these highlanders could explain
      their adaptation to altitude, allowing higher oxygen blood saturation at medium
      working loads and reducing the risk of neurological injury caused by a high
      ventilatory response when exercising at high intensity effort under extreme
      altitude environment.

PMID- 9776552
TI  - Extent of expiratory flow limitation influences the increase in maximal exercise
      ventilation in hypoxia.
AB  - Increasing ventilation (VE) during hypoxic exercise may help to defend arterial
      O2 saturation (SaO2) and VO2max however, many athletes experience limitations to
      ventilatory flow and are not able to increase VE at high workrates. Five of 19
      highly trained endurance athletes screened had < 5% of their tidal flow volume
      loop during maximal exercise meet the boundary set by their maximal resting flow
      volume loop. These five athletes were grouped as non-flow limited and compared to
      the five athletes who demonstrated the greatest percent of tidal volume flow
      limitation (56 +/- 11%) during maximal exercise (flow limited). Each athlete
      completed two incremental treadmill tests to exhaustion: normoxia and hypoxia
      (FI(O2) = 0.187). Non-flow limited athletes increased VE at VO2max from normoxia
      to hypoxia (140.9 +/- 13.4 vs. 154.7 +/- 11.9 L/min, P < 0.05), while flow
      limited athletes did not (159.5 +/- 9.4 vs. 162.3 +/- 6.0 L/min). The decline in
      SaO2 at VO2max from normoxia to hypoxia was not significantly different between
      groups. We conclude that athletes with little or no expiratory flow limitation
      are able to increase VE during maximal exercise in mild hypoxia, compared to
      athletes with significantly higher degrees of mechanical limitation. However this
      'mechanical ventilatory reserve' does not appear to influence the ability to
      defend SaO2 or VO2max during maximal exercise in mild hypoxia.

PMID- 9776553
TI  - The effect of hyperoxia on embryonic and organ mass in the developing chick
      embryo.
AB  - It is known that hyperoxia stimulates growth late in incubation when the chick
      embryo outgrows the O2 diffusion capacity. We wondered whether hyperoxia could
      have an effect in the early period prior to the stage where metabolism exceeds
      the oxygen diffusion capacity of the eggshell. For this we studied four groups of
      chicken eggs: control group (CG; n = 100) and three test groups (TGs) exposed
      during 48 h to 60% O2 on days 10, 14, and 18. In the CG, embryonic and organ mass
      (brain, heart, lungs, liver and intestine) were measured from day 10 until day 21
      of incubation. In the TGs embryonic and organ mass were obtained from 24 h after
      the start of hyperoxia exposure until the end of incubation. In all TGs the most
      striking growth rate acceleration was observed in the liver and intestine,
      maximum growth rate accelerations were respectively, 19 and 42% in TG1, 43 and
      173% in TG2 and 39% and 84 in TG3. In contrast, the brain was little affected by
      the hyperoxia exposure, the maximum growth rate acceleration was 14% in TG2. The
      results suggest that also in the middle of the incubation period O2 availability
      can be a limiting factor for growth, before metabolism exceeds the oxygen
      diffusion capacity of the eggshell.

PMID- 9776554
TI  - Postnatal development of respiratory function in lambs studied serially between
      birth and 8 weeks.
AB  - We have quantified developmental changes in major aspects of respiratory function
      in 12 pentobarbitone-sedated lambs by making repeated measurements during the
      first 8 postnatal weeks, between term birth and post-weaning. Pulmonary diffusing
      capacity for CO increased with age due to increases in both the diffusing
      capacity of the alveolar capillary membrane (Dm) and pulmonary capillary blood
      volume (Vc). Total lung capacity measured at a lung inflation pressure of 30
      cmH2O decreased from 74.4 +/- 3.2 ml/kg at 3 days to 47.2 +/- 2.9 ml/kg at 8
      weeks. Static respiratory system compliance, measured between FRC and TLC fell
      rapidly during the first 3 weeks, then remained unchanged; the early postnatal
      fall was largely due to a reduction in chest wall compliance as lung compliance
      was constant. FRC declined from 32.3 +/- 1.7 ml/kg at 3 days to 25.1 +/- 1.5
      ml/kg at 2 weeks, then fell to 21.4 +/- 1.2 ml/kg by 8 weeks. Specific pulmonary
      conductance (conductance/FRC) during mid-inspiration and mid-expiration did not
      change with age (0.195 +/- 0.012 and 0.194 +/- 0.019 L x sec(-1) x cmH2O(-1) x L(
      1)-FRC, respectively). Breathing frequency, and weight-adjusted tidal volume and
      minute ventilation declined after birth until 4 weeks after which they did not
      change. This study has shown that, using basic methodology, serial assessments of
      respiratory function can be obtained in sedated lambs from soon after birth. The
      age-related increase seen in pulmonary diffusing capacity is due to increases in
      both Dm and Vc, which are consistent with continuing alveolarisation. Our data on
      age-related changes in pulmonary function and volumes provide a reference for
      future studies on the effect of altered prenatal lung development on postnatal
      lung function in sheep.

PMID- 9776555
TI  - Allometric algorithms and the work of the heart.
AB  - In mammals, blood velocity at the aortic root varies little with body mass, M,
      and so the kinetic work is a constant fraction of the total work of the heart,
      and also of the metabolic rate of the animal. This happens because body
      metabolism and the cross-sectional area of the aortic root vary to the same power
      of M. But if metabolism increased with M to a higher power than area, aortic
      velocity would increase and kinetic work would become a greater fraction of total
      work in a large animal. In larger animals it could exceed pressure work at rest
      and even more so in exercise. But there is a limit to how much an increase in
      aortic area can balance an increase in metabolism without the aorta becoming
      ridiculously large. Also aortic area should not exceed ventricular area. These
      factors could dictate how high the power of M is in relation to the metabolism of
      an animal.

PMID- 9776556
TI  - Effect of alcohol and/or cocaine on blood glutathione and the ultrastructure of
      the liver of pregnant CF-1 mice.
AB  - Alcohol and cocaine are abused by the general population as well as by pregnant
      women. Since alcohol and cocaine are hepatotoxic, pregnant mice were used to
      study the effect of alcohol and/or cocaine on alanine aminotransferase (ALT) and
      aspartate aminotransferase (AST) and on liver ultrastructure. Also, blood
      glutathione (GSH) and GSH related enzymes such as glutathione reductase (GSH-Rx)
      and glutathione peroxidase (GSH-Px) were studied. The mice were treated with 0.6
      g/kg ethanol twice daily via gavage and/or 20 mg/kg of cocaine hydrochloride
      intravenously once daily. The treatment was from day 6 to 15 of gestation and
      these studies were performed at day 18. Our results indicated a significant
      increase in AST level after treatment with ethanol alone or in combination with
      cocaine. The blood GSH levels decreased significantly in all the treated groups
      compared to the control. The activity of GSH-Px was significantly decreased only
      in the ethanol and cocaine combination group compared to the control.
      Histopathological studies indicated that co-administration of ethanol and cocaine
      lead to a significant potentiation in liver toxicity as indicated by increased
      fatty infiltration.

PMID- 9776558
TI  - Similar cytogenetic effects of sodium-meglumine diatrizoate and sodium-meglumine
      ioxithalamate in lymphocytes of patients undergoing brain CT scan.
AB  - Cytogenetic effects of two ionic contrast media (CM), Urografin 76% a sodium
      meglumine diatrizoate, and Telebrix 38, a sodium-meglumine ioxythalamate, were
      tested on lymphocytes of patients undergoing brain CT Scan. Both compounds have
      approximately similar iodine concentrations. Chromosomal aberrations were scored
      in peripheral lymphocytes obtained from 15 patients undergoing brain CT with
      either urografin 76% or telebrix 38 before and after examination. Results showed
      no difference in aberration frequency for patients who underwent brain CT without
      contrast materials compared to controls. However, injection of CM resulted in a
      high frequency of chromosomal aberrations which significantly differed from
      controls (P < 0.05). The effect of urografin 76% appeared to be similar to
      telebrix 38. Therefore, both CM exhibited clastogenic effects on peripheral
      lymphocytes in vivo. An increase in chromosomal aberrations due to CM used in
      this study were similar to that reported for other ionic and non-ionic compounds.

PMID- 9776557
TI  - Fenofibrate modifies transaminase gene expression via a peroxisome proliferator
      activated receptor alpha-dependent pathway.
AB  - Fibrates modify the expression of genes implicated in lipoprotein and fatty acid
      metabolism via the peroxisome proliferator-activated receptor alpha(PPARalpha),
      leading to reductions in serum triglycerides and cholesterol. The expression of
      certain genes regulated by PPARalpha have been shown to be modified in a species
      dependent manner. Aspartate aminotransferase (AspAT or GOT) and alanine
      aminotransferase (AlaAT or GPT) are enzymes involved in intermediate metabolism
      in all cells and in hepatic gluconeogenesis. These enzymes are also widely used
      as serum markers of possible tissue damage. This study investigated whether
      fenofibrate could modify the expression of liver AspAT and/or AlaAT and thus
      possibly alter transaminase levels independently of a cytotoxic effect. In human
      Hep G2 cells, fenofibrate increased cytosolic AspAT (cAspAT) activity by 40% and
      AlaAT activity by 100%, as well as both mRNAs. Nuclear run on assays showed that
      this effect was, at least in part, transcriptional. Increases in mRNA were also
      observed in human hepatocyte cultures at concentrations of the drug attained in
      patients. In C57BL/6 mice, fenofibrate decreased cAspAT and cAlaAT mRNA, while
      these effects were abolished in PPARalpha knock-out mice. In conclusion,
      fenofibrate has been shown to modify cAspAT and AlaAT gene expression in a
      species and PPARalpha dependent manner. This is the first demonstration that
      cAspAT and AlaAT activities may be pharmacologically altered, independently of a
      toxic phenomenon.

PMID- 9776559
TI  - Formation of liver microsomal MDA-protein adducts in mice with chronic dietary
      iron overload.
AB  - Lipid peroxidation has been proposed to be a major mechanism involved in the
      pathophysiology of hepatic iron overload. Hepatic microsomal lipid peroxidation
      has been demonstrated in animals with dietary iron overload, and major products
      of lipid peroxidation with known cytotoxicity, such as malondialdehyde (MDA), may
      be involved in iron-induced hepatocellular injury by covalent binding to
      microsomal proteins. This investigation examined whether DBA/2Ibg mice fed a diet
      enriched with ferrocene-iron for 16 weeks, results in hepatic lipid peroxidation,
      and if liver microsomes contain proteins adducted by MDA. Chronic iron feeding to
      mice resulted in a severe hepatic iron overload with hepatic stores of iron 12
      fold greater than those measured in control mice and a three-fold increase in
      hepatic concentrations of MDA, indicating the occurrence of iron-induced lipid
      peroxidation in vivo. Hepatic collagen content was increased by over three-fold
      (p < 0.05) in iron-fed mice as compared to control animals, suggesting increased
      fibrogenesis. Using rabbit antiserum specific for MDA amine protein adducts and
      immunoprecipitation-Western blotting, we documented formation of 10 liver
      microsomal proteins adducted by MDA in iron overload mice (approximate molecular
      weights; 214, 140, 129, 121, 103, 83, 62, 60, 48, and 43-kD). Control mice did
      not exhibit positive immunostaining for these protein adducts. The incubation of
      synthetic MDA with liver microsomes isolated from untreated mice demonstrated
      formation of MDA-adducted proteins with molecular weights comparable to those
      detected following in vivo iron overload. The data from this animal study are the
      first to demonstrate that lipid-derived aldehydes produced from hepatic iron
      overload in vivo, covalently bind and hence, chemically modify numerous proteins
      in microsomes. These data suggest that MDA modified proteins in microsomes may
      play a role in a sequence of events that lead to cell injury during metal-induced
      liver damage.

PMID- 9776560
TI  - Amiodarone-induced disruption of hamster lung and liver mitochondrial function:
      lack of association with thiobarbituric acid-reactive substance production.
AB  - Amiodarone (AM) is an efficacious antidysrhythmic agent that is limited
      clinically by numerous adverse effects. Of greatest concern is AM-induced
      pulmonary toxicity (AIPT) due to the potential for mortality. Mitochondrial
      alterations and free radicals have been implicated in the etiology of AM-induced
      toxicities, including AIPT. Isolated hamster lung and liver mitochondria were
      assessed for AM-induced effects on respiration, membrane potential, and lipid
      peroxidation. AM (50-400 microM) stimulated state 4 (resting) respiration at
      complexes I and II of tightly coupled lung mitochondria, with higher
      concentrations (200 and 400 microM) resulting in a subsequent inhibition. This
      biphasic effect of AM (200 microM) was also observed with isolated liver
      mitochondria. Only inhibition of respiration was observed with AM (50-400 microM)
      in less tightly coupled lung mitochondria. Based on safranine fluorescence, 200
      microM AM decreased lung mitochondrial membrane potential (p < 0.05), while a
      concentration-dependent (50-200 microM) decrease of membrane potential was
      observed with liver mitochondria exposed to AM (p < 0.05). Formation of
      thiobarbituric acid-reactive substances (TBARS) was not altered by AM (50-400
      microM) in incubations lasting up to 1 h. These results indicate that lipid
      peroxidation, as indicated by levels of TBARS, does not play a role in AM-induced
      alterations in mitochondrial respiration and membrane potential.

PMID- 9776561
TI  - Comparative tumorigenicity of 1- and 3-nitrobenzo[a]pyrenes, and 3,6- and 1,6
      dinitrobenzo[a]pyrenes in F344/DuCrj rats.
AB  - Our earlier study revealed that 1- and 3-nitrobenzo[a]pyrene (NBP), 1,6- and 3,6
      dinitrobenzo[a]pyrene (DNBP), nitrated derivatives of benzo[a]BP (BP), are
      present in the environment. These derivatives are potent mutagens for Salmonella
      tester strains and we have preliminarily reported them to be carcinogenic in
      F344/DuCrj rats. In this study, the tumorigenic action of 1- and 3-NBP, 1.6- and
      3,6-DNBP, and BP induced by subcutaneous injection into rats was found to differ
      according to the NO2-substitution in the BP structure. The chemicals were
      suspended in equal volumes of beeswax and tricaprylin, and rats were
      subcutaneously injected with single doses of 500, 1000, and 2000 microg for 1-
      and 3-NBP, and of 8, 40, 200, and 1000 microg for 3,6- and 1,6-DNBP, and BP as a
      positive control. 3,6-DNBP and BP induced tumors in a dose-dependent manner at
      the injection site. Rats given 1000 microg of 3,6-DNBP (2924 nmol) and BP (3968
      nmol) developed subcutaneous tumors at the rate of 70 and 80%, respectively, and
      those given a minimum dose of 23 nmol for 3.6-DNBP and 32 nmol for BP per rat
      developed tumors at a rate of 4.8 and 18.2%, respectively. However, rats given
      500 and 1000 microg of 1- and 3-NBP did not develop any tumors while those given
      a high dose, 2000 microg, of each chemical developed tumors at only one of ten
      animals used. It was concluded, therefore, that these chemicals are weak
      carcinogens. Histologically, most of the tumors were malignant fibrous
      histiocytomas. Rats given various doses of 1,6-DNBP did not develop any tumors at
      the injection site. The failure of 1,6-DNBP to induce tumors may involve its
      metabolites because of the lower mutagenicity of its reduction products, 1
      nitroso-6-NBP and 1-amino-6-NBP. It is suggested, therefore, that
      tumorigenicities of NBPs and DNBPs differ according to the NO2-substitution on
      the chemical structure, which may be due to the possible nitroreduction of the
      chemicals.

PMID- 9776562
TI  - Influence of diet restriction and tumor promoter dose on cell proliferation,
      oxidative DNA damage and rate of papilloma appearance in the mouse skin after
      initiation with DMBA and promotion with TPA.
AB  - The mouse skin tumor initiation-promotion model was used to investigate the
      protective effect of diet restriction in mechanistic and quantitative terms. A
      total of five groups of 14 male NMRI mice were initiated with 100 nmol 7,12
      dimethylbenz[a]anthracene (DMBA) and promoted twice weekly with 2.5, 1.25, or
      0.625 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA). Food intake was ad libitum
      (all 3 TPA dose levels) or restricted to 70% (high and intermediate TPA dose
      levels). Time of appearance of the first papilloma was recorded for each mouse.
      Two weeks later, an osmotic minipump delivering 5-bromo-2'-deoxyuridine (BrdU)
      was implanted and the mouse was killed after 24 h. Cell proliferation in the
      epidermis was assessed by immunohistochemistry for BrdU incorporated into DNA. 8
      hydroxy-2'-deoxyguanosine (8-OH-dG) in epidermal DNA was determined by
      HPLC/electrochemical detection. The median latency time (t50) for the appearance
      of skin papilloma in the high-, intermediate-, and low-dose TPA groups fed ad
      libitum was 9, 15.5, and 23.5 weeks, respectively. The diet-restricted groups
      (high and intermediate TPA dose) showed t50 values of 16 and 26 weeks. Therefore,
      diet restriction to 70% had approximately the same protective effect as reducing
      the dose of TPA by a factor of two. Both the rate of cell proliferation and the
      level of 8-OH-dG in the epidermis increased with the dose of TPA. Median values
      were increased 3- to 4-fold at the highest dose. In controls, but not in TPA
      treated animals, diet restriction resulted in a decrease for both markers, by 25
      and 40% for the labeling index for cell division and the level of 8-OH-dG,
      respectively. Both markers showed an inverse relationship with the median
      papilloma latency time. On an individual basis, the correlation was significant
      in some groups, but only for the labeling index. The data indicate that
      protection from the skin tumor-promoting effect of TPA by diet restriction could
      be based more on a reduction of the rate of cell division than on a reduction of
      oxidative DNA damage.

PMID- 9776563
TI  - Quantitative analysis of liver peroxisomes in rats intoxicated with
      peroxisomicine-A1.
AB  - Peroxisomes are single-membrane-bound organelles present in almost all eukaryotic
      cells. Hypolipidemic agents such as clofibrate, herbicides and plasticizers
      induce an increase in the number and size of peroxisomes from mammalian cells.
      However, there is no evidence of drugs causing a decrease in the number of these
      organelles. In this paper, we report the effect in vivo of toxin T-514 extracted
      from the plant Karwinskia humboldtiana, now re-named peroxisomicine-A1, on
      hepatic peroxisomes from rats intoxicated with this compound. Rats were treated
      with a single dose of 25 mg/kg of peroxisomicine-A1 and at different times were
      killed by decapitation. For the peroxisomal counting, liver tissue sections from
      control and treated rats were processed for the localization of catalase in
      peroxisomes. The results of the quantitative analysis demonstrated a significant
      decrease in the number of liver peroxisomes from rats intoxicated with
      peroxisomicine-A1. This finding suggests that peroxisomicine-A1 as in yeast,
      causes a damage to mammalian peroxisomes. The diminution in the number of
      peroxisomes could be a consequence of damage to the organelle, which is further
      removed by an autophagic process.

PMID- 9776564
TI  - Freshly generated stainless steel welding fume induces greater lung inflammation
      in rats as compared to aged fume.
AB  - It has been previously reported that both short- and long-lived reactive oxygen
      species (ROS) are present on the surface of freshly generated fumes. The
      objective of this study was to determine if freshly formed welding fume induces
      greater lung inflammation and injury in rats due to the presence of reactive
      oxygen species than aged welding fume. Fume was collected during gas metal arc
      welding using a stainless steel consumable electrode and found to be of
      respirable size with a mean diameter of 0.77 microm +/- 0.48. Male CD/VAF rats
      were dosed intratracheally with the welding fume 30 min (fresh) and 1 and 7 days
      (aged) after fume collection at a dose of 1.0 mg/100 g b wt. Bronchoalveolar
      lavage (BAL) was performed 24 h post-instillation. Lung injury and inflammation
      were assessed by measuring the concentration of neutrophils, albumin, lactate
      dehydrogenase (LDH), and glucosaminidase (GLU) in the recovered BAL fluid. More
      neutrophils and enhanced GLU activity were observed for the 'fresh' group as
      compared to both 'aged' groups (P < 0.05). Slight, but not significant,
      elevations were seen in albumin content and LDH activity for the 'fresh' group as
      compared to the 'aged' groups. No significant differences were observed for any
      of the parameters when fume aged for 1 and 7 days were compared. When the 'fresh'
      and 'aged' fumes (12.5, 25, and 50 microg/ml) were suspended in
      dichlorofluorescin (15 microM), a probe which becomes fluorescent when oxidized,
      the concentration-dependent increases in fluorescence were greater for the
      'fresh' fume versus the 'aged' fumes. We have demonstrated that freshly generated
      stainless steel welding fume induces greater lung inflammation than 'aged' fume.
      This is likely due to a higher concentration of ROS on fresh fume surfaces.

PMID- 9776565
TI  - Further evaluation of developmental toxicity of di-n-butyl phthalate following
      administration during late pregnancy in rats.
AB  - The objective of this study was to further evaluate the developmental toxicity of
      di-n-butyl phthalate (DBP) administered during the second half of pregnancy.
      Pregnant rats were fed a diet containing DBP at a dose of 0 (control), 0.5, 1.0
      or 2.0% ad libitum on days 11-21 of pregnancy. Average daily intakes of DBP were
      331, 555 and 661 mg/kg for the 0.5, 1.0 and 2.0% groups, respectively. No
      significant changes induced by DBP were detected in the incidence of
      postimplantation loss and numbers of live fetuses and of resorptions and dead
      fetuses. The weights of male and female fetuses at 2.0% DBP were significantly
      decreased. The incidences of fetuses with cleft palate and fetuses with fusion of
      the sternebrae at 2.0% DBP and fetuses with undescended testes at 1.0 and 2.0%
      DBP were significantly increased. There were significant decreases in the
      anogenital distance (AGD) of male fetuses in the 1.0 and 2.0% DBP groups, also.
      AGD of female fetuses in the DBP-treated groups was comparable to that in the
      control group. It was concluded that DBP administered during the second half of
      pregnancy produced adverse effects on the reproductive development in male
      fetuses.

PMID- 9776566
TI  - Elevated frequency of sister chromatid exchanges in lymphocytes of victims of the
      Tokyo sarin disaster and in experiments exposing lymphocytes to by-products of
      sarin synthesis.
AB  - More than 5000 passengers of Tokyo subway trains were injured with toxic
      chemicals including the nerve gas sarin. Most of the victims examined had marked
      miosis and decreased serum cholinesterase activity. To monitor the genetic
      aftereffects of sarin exposure, we measured sister chromatid exchanges (SCEs) of
      the victims using peripheral blood lymphocytes. The frequency of SCEs was
      significantly higher in the victims than in the control group. Analyzing results
      using samples of urine from the victims suggested that the victims were exposed
      to not only sarin per se, but by-products of sarin synthesis, i.e. diisopropyl
      methylphosphonate (DIMP), diethyl methylphosphonate (DEMP) and ethyl isopropyl
      methylphosphonate (EIMP). Thus, the in vitro SCE-inducing effect of DIMP, DEMP
      and EIMP was examined using human lymphocytes and we obtained positive results.

PMID- 9776567
TI  - Effects of dienogest (a synthetic steroid) on coagulation, fibrinolysis, and
      platelet aggregation in female monkeys.
AB  - We investigated the effects of dienogest (0.1-10 mg/kg per day, p.o.) on
      coagulation, fibrinolysis and platelet aggregation in female rhesus monkeys.
      Then, we also examined those of medroxyprogesterone acetate (MPA, 10 mg/kg per
      day, p.o.) or danazol (10-1000 mg/kg per day, p.o.) on these parameters in the
      same species. In addition, we assessed the effects of dienogest (1 and 3 mg/kg
      per day, p.o.) or MPA (10 mg/kg per day, p.o.) on platelet aggregation and
      platelet lipids in female cynomolgus monkeys. At doses of 0.3 mg/kg or greater,
      dienogest increased the levels of several coagulation and anticoagulation
      factors, but had no effect on the prothrombin time, activated partial
      thromboplastin time, fibrinolysis, or platelet aggregation. MPA (10 mg/kg) had no
      effect on coagulation or fibrinolysis, but significantly potentiated platelet
      aggregation in response to ADP and collagen and also increased the platelet
      cholesterol-to-phospholipid ratio. Danazol (10 mg/kg or more) increased the
      activities of coagulation factors V, VII, VIII, X, XI, and XII in comparison to
      dienogest and MPA. Consequently, dienogest caused less potentiation of platelet
      aggregation than MPA and less potentiation of coagulation than danazol.

PMID- 9776569
TI  - Comment on "Psychological and somatic subjective symptoms as a result of
      dermatological patch testing with metallic mercury and phenyl mercuric acetate"
      by J.A. Marcusson, Toxicology Letters 84 (1996) 113-122.

PMID- 9776568
TI  - Serum and liver concentrations of tumor necrosis factor alpha and interleukin
      1beta following administration of carbon tetrachloride to male rats.
AB  - Inflammatory cytokines are recognized as early mediators of tissue damage and
      repair. The purpose of this study was to determine the effects of carbon
      tetrachloride administration on tumor necrosis factor-alpha (TNF-alpha) and
      interleukin 1beta (IL-1beta) concentrations in serum and liver of rats.
      Administration of 0.2 ml/kg, i.p., of CCl4 to male Fischer 344 rats caused modest
      increases in serum levels of both cytokines; elevations of TNF-alpha were
      statistically significant at 4 and 12 h, and elevations of IL-1beta were
      statistically significant at 24 h. Although CCl4 produced substantial increases
      in liver IL-1beta concentrations (more than 3-fold), levels of TNF-alpha were not
      affected. Treatment with 0.1, 0.32 or 1.0 ml/kg of CCl4 produced dose-dependent
      increases in serum alanine aminotransferase (ALT) and sorbitol dehydrogenase
      (SDH) activities, but serum cytokine concentrations were not dose-dependent and
      did correspond with serum ALT and SDH activities. The results suggest that IL
      1beta production in rat liver is stimulated by hepatotoxic doses of CCl4.
      Production of TNF-alpha may also be induced, but the source of TNF-alpha in serum
      could be a tissue or organ other than liver.

PMID- 9776570
TI  - F(ab')2 molecules made from Escherichia coli produced Fab' with hinge sequences
      conferring increased serum survival in an animal model.
AB  - Fab's with hinges based on the human gamma1 sequence containing 1, 2, or 4
      cysteines have been produced by high level Escherichia coli periplasmic
      secretion, and coupled in vitro by reduction/oxidation to form F(ab')2. We find
      that the F(ab')2 made with hinges containing 2 or 4 cysteines have a high level
      (approximately 70%) of multiple disulphide bonds. These F(ab')2 molecules have an
      increased pharmacokinetic stability as measured by area under the curve compared
      to those made by direct coupling through a single disulphide bond. One particular
      molecule containing 4 hinge cysteines has a greater pharmacokinetic stability
      than a F(ab')2 formed by chemical cross-linking. F(ab')2 made from the Fab' with
      4 hinge cysteines is also relatively resistant to chemical reduction in vitro
      allowing partial reduction to expose reactive hinge thiols. These hinge sequences
      provide a simple method for producing robust F(ab')2 in vitro, obviating the need
      to use chemical cross-linkers, and provide a route to hinge specific chemical
      modification with thiol-reactive conjugates.

PMID- 9776571
TI  - A cytofluorometric method for the simultaneous detection of both intracellular
      and surface antigens of apoptotic peripheral lymphocytes.
AB  - The aim of this study was to define a simple and reliable method to detect
      simultaneously surface and intracellular antigens in apoptotic peripheral human
      lymphocytes. This approach requires a permeabilizing procedure for intracellular
      access of mAbs, which raises the important question of the influence of this
      procedure on parameters which identify apoptotic cells and on the surface
      expression of antigens. We compared the effects of three currently used
      permeabilizing methods (saponin quillaia bark 0.05%, Triton X-100 0.1, ethanol
      70%) on the quantification of apoptotic lymphocytes, defined according to FSC/SSC
      criteria or following 7-AAD staining, and on the detection of surface CD3, CD4,
      CD8, Fas, CD45R0 molecules. The combined detection of these surface antigens with
      intracellular molecules, including Bcl-2 and cytokines (IFNgamma, TNFalpha, IL-2)
      was also analysed in the context of these three permeabilizing procedures. All
      the experiments were performed on PBMC from HIV-infected donors, known to undergo
      excessive apoptosis following short-term culture. We report that permeabilization
      with saponin is the only procedure which allows: (1) the preservation of
      lymphocyte morphology determined by the FSC/SSC parameters; (2) the
      quantification of apoptotic lymphocytes following 7-AAD staining; (3) a reliable
      surface immunophenotyping, maintaining a good antibody binding capacity (ABC);
      (4) the proper detection of intracellular membrane bound antigens (Bcl-2) and
      intracellular cytokines (IFNgamma, TNFalpha, IL-2); (5) the combined detection of
      apoptotic nuclei, surface antigens and intracellular molecules. Altogether these
      observations demonstrate that the simultaneous analysis of extracellular and
      intracellular antigens in apoptotic cells belonging to a complex lymphoid
      populations such as PBMC can be readily overcome provided the detergent used for
      cell permeabilization is appropriate and the successive staining procedures
      performed in a defined order.

PMID- 9776572
TI  - Bone marrow cellular composition in Listeria monocytogenes infected mice detected
      using ER-MP12 and ER-MP20 antibodies: a flow cytometric alternative to
      differential counting.
AB  - Detailed assessment of bone marrow cellular composition is essential in the
      evaluation of various experimental in vivo systems, such as expression of
      transgenes, null mutations and stimulation of host defence in infection.
      Traditional morphological analysis of mouse bone marrow is laborious, requires
      specific cytological expertise, and is somewhat subjective. As an alternative, we
      have examined whether double labelling of bone marrow with the anti-precursor
      monoclonal antibodies ER-MP12 and ER-MP20 could be used for differential analysis
      by flow cytometry, as these antibodies define six relatively homogeneous cell
      populations in mouse bone marrow. Following a sublethal infection of mice with
      Listeria monocytogenes, we monitored changes in cellular composition of the bone
      marrow at various time points in three ways: differential morphological count;
      single-color flow cytometric analysis using markers for the myeloid, erythroid
      and lymphoid lineages; and double labelling with ER-MP12 and ER-MP20. As
      expected, the bone marrow composition changed dramatically during infection,
      leading to an increase of myeloid cells which peaked after 1 week of infection.
      Data determined by ER-MP12/20 flow cytometric analysis appeared to be in close
      agreement with both morphology and lineage marker analysis. In addition, ER
      MP12/20 analysis provided more detailed information with regards to the presence
      of early myeloid precursors compared to lineage marker analysis. These data show
      that flow cytometric analysis of bone marrow using ER-MP12 and ER-MP20 monoclonal
      antibodies provides a relatively simple, rapid and objective assay when
      evaluating cellular composition in the bone marrow of the mouse.

PMID- 9776573
TI  - Detection of and discrimination between total and free human interleukin-4 and
      free soluble interleukin-4 receptor by ELISA.
AB  - Interleukin-4 (IL-4) signaling is initiated by binding of IL-4 to the high
      affinity IL-4 receptor alpha-chain and subsequent interaction with the common
      gamma-chain. Soluble forms of the extracellular domain of the alpha-chain (sIL
      4R) were shown to be present in biological fluids and, dependent on the
      concentration, enhance or inhibit IL-4 activity by forming IL-4/sIL-4R complexes.
      To discriminate between free and potentially active IL-4 from the inactive and
      complexed form, we have established a set of new ELISA systems for the
      measurement of human IL-4 in its distinct forms. To select suitable pairs of anti
      IL-4 antibodies, a chequerboard interference analysis with six highly-selective
      human IL-4 specific monoclonal antibodies was performed. For the determination of
      total IL-4, a monoclonal capture antibody was used that binds IL-4 outside the
      binding site of the IL-4R alpha-chain. Another antibody recognizing an epitope of
      the alpha-chain binding site was chosen for the detection of free IL-4. The
      binding of this antibody was inhibited in a dose-dependent fashion by recombinant
      sIL-4R. Assays for both total and free IL-4 exhibited a sensitivity of 8 pg/ml
      and a dynamic range up to 1000 pg/ml. Human sIL-4R was detected by two monoclonal
      antibodies directed against different epitopes. This ELISA was inhibited by
      recombinant IL-4 suggesting the measurement of predominantly free sIL-4R.
      Complexes between soluble IL-4R and IL-4 were detected by a monoclonal anti-sIL
      4R antibody in combination with an anti-IL-4 antibody. When supernatants of
      activated T cells were analyzed, the majority of the IL-4 was in free form. The
      amount of complexed IL-4 was low as indicated by the fact that most of total IL-4
      could be detected as free IL-4. Although values obtained for complexed IL-4
      correlated with the difference between total and free IL-4, precise values could
      not be determined, presumably due to the dynamic nature of the complex between
      the two proteins. We suggest that the ability to quantitate total and free IL-4
      in combination with sIL-4R may provide a new insight of the role that IL-4 plays
      in different pathophysiological conditions.

PMID- 9776574
TI  - The matrix effects on kinetic rate constants of antibody-antigen interactions
      reflect solvent viscosity.
AB  - This study describes the influence of different matrices on two model antibody
      antigen interactions; that between beta2microglobulin and anti
      beta2microglobulin, and that of rabbit anti mouse Fc fragment (RAMFc) with mouse
      IgG. The matrices investigated were; phosphate-buffered saline pH 7.4 containing
      0.05% Tween 20 detergent, horse serum, a 50:50 mixture of phosphate-buffered
      saline/Tween 20 and horse serum, and four glycerol solutions of differing
      concentrations. A recently developed optical biosensor, the IAsys, was used to
      monitor the interactions in real-time and provide precise determinations of
      k(ass), k(diss) and KA values. The results show that the rates of association and
      dissociation for the two different antibody:antigen models are significantly
      affected by the surrounding matrix. Glycerol of known viscosity was used as a
      matrix in both models to show that this effect is attributable to the viscosity
      as opposed to proteins present in the matrix. The viscosity of the matrix has
      also been shown to have an apparent influence upon the overall
      equilibrium/affinity constant for the interaction, with measurements of KA
      tending to increase with viscosity. The significant effects of matrix on kinetic
      rate constants for antibody-antigen interactions shown here have important
      implications in the use of immunoassays where non-equilibrium measurements are
      made in serum matrices.

PMID- 9776575
TI  - Apoptosis detection by annexin V binding: a novel method for the quantitation of
      cell-mediated cytotoxicity.
AB  - Current standard methods for the measurement of cell-mediated cytotoxicity rely
      on radioactive tracers, which either detect the release of cytoplasmic contents
      after plasma membrane disintegration by dying cells (51Cr release), or retained
      DNA by living cells (the JAM test). In this study, the annexin V binding assay of
      early apoptosis was applied to measure cell-mediated cytotoxicity. Primed human
      lymphocytes were examined for their ability to lyse either xenogeneic pig
      endothelial or allogeneic human PBMC target cells by assaying annexin V binding
      and the results compared with those obtained by the JAM test. Assaying annexin V
      binding by indirect immunofluorescence was demonstrated to be more sensitive and
      faster than the JAM test, which is a well-described, sensitive and simple assay
      for DNA fragmentation and cell death. However, the annexin V binding method was
      considered a more accurate measurement of absolute cytotoxicity as individual
      cell lysis was detected directly. In other methods, cytotoxic activity was
      calculated indirectly as a percentage of retained or released radioactive label.
      In addition, the apoptosis induced by the cell-mediated cytotoxicity can be
      visualized by this method thereby allowing a more accurate and sensitive
      quantitation of the number of apoptotic cells present when low effector to target
      ratios are used. These advantages make the annexin V binding method superior to
      other conventional cytotoxicity assays, particularly in situations where effector
      cells can be easily distinguished or separated from target cells.

PMID- 9776576
TI  - A modification of the JAM test is necessary for a correct determination of
      apoptosis induced by FasL+ adherent tumor cells.
AB  - Tumor cells from several organs including colon have recently been shown to
      express Fas ligand (FasL) in vitro and in vivo. The expression, which in some
      tumours occurs de novo, was suggested to facilitate immune escape of malignant
      cells by killing tumor-infiltrating lymphocytes via Fas-FasL-induced apoptosis.
      An argument to support this hypothesis is the detection of tumor cell-induced
      apoptosis in Jurkat cells (as model T cells) by means of the widely used JAM
      test. In the present work the validity of this test for the analysis of colon
      carcinoma cell-mediated apoptosis in Jurkat cells was scrutinized in detail. The
      presented data show that the JAM test as described previously is prone to false
      positive detection of apoptosis, when adherent epithelial cells are used as
      effectors. Furthermore, three lines of evidence indicated that several FasL+
      colon carcinoma cell lines did not induce detectable apoptosis in Jurkat cells in
      vitro. We conclude that: (1) The JAM test must be modified for testing DNA
      fragmentation induced through adherent effector cells and (2) FasL+ colon
      carcinoma cells may be unable to induce apoptosis in vitro.

PMID- 9776577
TI  - An ELISA to determine the biodistribution of human monoclonal antibody in tumor
      xenografted SCID mice.
AB  - An ELISA technique was developed to assay the distribution of native human
      monoclonal antibodies (mAbs) in tumor-xenografted SCID mice. This was used in an
      investigation of its potential as an alternative to the conventional
      radioisotopic technique for mAb biodistribution assays which would be simpler to
      implement and might yield results in closer accord with actual mAb activity
      because it is based on the use and detection of the native mAbs rather than their
      radioisotope-coupled immunoconjugates. SCID mice bearing xenografted tumors of
      the human lung adenocarcinoma cell line A549 received injections via the tail
      vein of four human mAbs that had been obtained from human-mouse heterohybridomas
      and were known to be reactive with A549. The biodistribution of the mAbs was
      assayed by the ELISA technique seven days after the mAb injection. The assay
      yielded tumor/serum ratios for the four reactive mAbs which were in the range of
      three to six and tumor mAb levels which were in the range of 0.28 to 0.92 %ID/g
      (percent of injected mAb dose per gram of tumor). The tumor mAb levels were thus
      lower than the levels commonly found by radioisotopic assay, and further
      investigation is desirable to determine the cause of the difference. The results
      indicate that ELISA can provide a simple, practical means of investigating the
      biodistribution of human mAbs in mice bearing xenografted carcinomas. The
      application of this procedure would obviate the need for the complex facilities
      and procedures associated with radioisotopic labelling and assay.

PMID- 9776578
TI  - A highly sensitive and specific assay using a novel human growth hormone cDNA
      reporter gene regulated by the human interleukin-4 inducible germline epsilon
      transcript promoter.
AB  - We have successfully developed a highly sensitive and specific assay system for
      human interleukin-4 (IL-4) regulated gene expression. It is based on a human
      Jijoye cell line with the germline epsilon transcript promoter joined to the
      human growth hormone (hGH) cDNA. The germline epsilon transcript promoter is
      responsive to IL-4 and involved in immunoglobulin heavy chain class switching. We
      cloned hGH complementary DNA (cDNA) as the reporter gene instead of using
      conventional hGH genomic DNA which failed to generate any IL-4 inducible clone in
      human Jijoye cells. The two IL-4 inducible cell lines with the hGH cDNA reporter
      show high signal/noise ratio for IL-4-mediated induction (60-90 fold). The
      response to IL-4 is dose-dependent with ED50 of 10 pM. As expected, there is no
      response to other human cytokines and growth factors, as well as mouse IL-4. The
      mutant hIL-4 antagonist hIL-4.Y124D inhibits the induction mediated by native hIL
      4. These IL-4 inducible cell lines provide a sensitive, specific assay system to
      study IL-4-regulated gene expression, and in particular the regulation of the
      germline epsilon promoter.

PMID- 9776579
TI  - Establishment of the cells useful for murine interleukin-18 bioassay by
      introducing murine interleukin-18 receptor cDNA into human myelomonocytic KG-1
      cells.
AB  - We genetically engineered human myelomonocytic KG-I cells by introducing cDNA of
      murine interleukin-18 receptor (MuIL-18R) and established human cells which were
      capable of responding to MuIL-18. These cells expressed larger number of MuIL-18R
      (> 13,000 sites/cell) than intrinsic human IL-18 receptor (HuIL-18R) (< 2,500
      sites/cell). And the cells responded to MuIL-18 as well as to HuIL-18 in a dose
      dependent manner, and produced large amounts of interferon-gamma (IFN-gamma). We
      could estimate the amount of murine IL-18 based on the amounts of IFN-gamma
      produced by these cells. The stoichiometry was observed up to 150 ng/ml of MuIL
      18. By using these cells, a large amount of MuIL-18 (448 +/- 89.2 ng/ml) was
      detected in sera of Propionibacterium acnes (P. acnes)/lipopolysaccharide (LPS)
      treated endotoxic mice (the same conditions in which IL-18 was first identified).
      These cells provide us with a useful tool for determining the bioactivity of MuIL
      18.

PMID- 9776580
TI  - On-line flow displacement immunoassay for fatty acid-binding protein.
AB  - In standard displacement flow immunoassays the analyte in the sample creates an
      active dissociation of labelled antigens (or antigen homologues) from an antigen
      binding site of an immobilized antibody, after which the labelled substance is
      measured downstream. Such systems have been described for molecules up to 1 kDa.
      In this study, we demonstrate displacement in a flow system for the detection of
      a small protein, cytoplasmic heart-type fatty acid-binding protein (15 kDa), a
      plasma marker for myocardial injury. The displacement system uses an inverse set
      up: enzyme labelled monoclonal antibodies are associated to immobilized antigen,
      and are displaced by analyte in the sample. The system permits detection of both
      physiological (2-12 microg l(-1)) and pathological concentrations (12-2000 microg
      l(-1)) of fatty acid-binding protein in an on-line flow system.

PMID- 9776581
TI  - Inhibition of nonspecific binding of fluorescent-labelled antibodies to human
      eosinophils.
AB  - Eosinophils and their products play a major role in inflammatory reactions
      associated with asthma and allergic diseases. There is a growing body of evidence
      that eosinophils synthesize, store, and release bioactive cytokines and
      chemokines with the potential to contribute to local inflammatory changes.
      Fluorescein isothiocyanate (FITC) has been widely used as an immunofluorescent
      conjugate for antibodies specific for detection of these molecules. However, FITC
      is an ionic fluorochrome (negatively charged) which binds strongly to positively
      charged eosinophil granule proteins. We developed new methods to prevent charge
      based interactions of ionic fluorochromes with granule proteins, and optimised
      immunofluorescent staining techniques for eosinophils. An antibody to interleukin
      6 (IL-6) was used to optimise this procedure for eosinophil-derived granule
      proteins. We attempted to block nonspecific binding of FITC-labelled anti-IL-6
      using normal human IgG, foetal calf serum (FCS), bovine serum albumin (BSA), and
      goat, horse, and normal human sera at concentrations ranging between 1-10%. Only
      human IgG (2%; 20 mg/ml) was able to reduce background fluorescence. These
      results were confirmed using Texas Red conjugates. We also used antibodies
      conjugated to a nonionic fluorochrome, BODIPY FL, to detect IL-6 in eosinophils.
      Unlike FITC, BODIPY FL-conjugated antibodies did not require strong blocking
      conditions (2% BSA). We recommend that a neutral fluorochrome (BODIPY FL) should
      be used for immunofluorescence studies in eosinophils. Alternatively, strong
      blocking conditions may be used to decrease background binding of FITC-conjugated
      antibodies.

PMID- 9776582
TI  - Removal of erythroid cells from umbilical cord blood mononuclear cell
      preparations using magnetic beads and a monoclonal antibody against glycophorin
      A.
AB  - Umbilical cord blood mononuclear cells isolated by density centrifugation are
      contaminated by erythrocytes and nucleated erythroid precursors which may exceed
      50% of the total cell population, and thus interfere with phenotypic, functional
      and mRNA analyses. Lysis with hypotonic ammonium chloride can overcome this
      problem, but interferes with lysosomal function and should be avoided when cell
      preparations are intended for functional studies. The aim of this study was to
      develop a technique for removing erythroid cells from cord blood mononuclear cell
      preparations that would be as effective as ammonium chloride lysis but would not
      affect cellular function. This paper describes a method using 10F7, a mouse
      monoclonal antibody against human glycophorin A, and magnetic beads coated with
      anti-mouse immunoglobulin. The population of cord blood mononuclear cells
      recovered using this technique was of high purity, good yield and viability, and
      the cells responded appropriately to stimulation in vitro. To maximise cost
      effectiveness, purification with magnetic beads could be performed after two
      density separations to reduce the quantity of beads required.

PMID- 9776583
TI  - Two high-affinity monoclonal IgG2a antibodies with differing thermodynamic
      stability demonstrate distinct antigen-induced changes in protein A-binding
      affinity.
AB  - Two IgG2a monoclonal antibodies (G10 and F11) are described which have similar
      affinity for human spleen ferritin and identical protein A-binding affinity. The
      two mAbs display changes in protein A-binding affinity following binding of the
      antigen to its specific recognition site in the variable domains. However, while
      antigen-induced conformational changes in G10 enhance its affinity to protein A,
      interaction of F11 with ferritin results in a significant decrease in protein A
      binding affinity. In contrast to the IgG2a antibodies, using a mouse IgG1
      antiferritin antibody (C5) high-affinity binding of the antigen does not change
      an inherently low ability to bind protein A. Differential scanning calorimetry
      revealed that the enthalpy and Gibb's free energy of thermal unfolding for G10
      was 19% and 23% higher, respectively, than the corresponding parameters for F11.
      The lower structural energetics of F11 are associated with the absence of a
      calorimetrically revealed folding unit, which may be responsible for interactions
      between the antigen-binding site and the protein A-binding site. This study
      provides the first demonstration that functionally significant interactions
      between two recognition sites in antibodies of the same subclass can be modulated
      by subclass-independent structural variations associated with different
      thermodynamic stability.

PMID- 9776584
TI  - A simple and robust method for the complete dissociation of HIV-1 p24 and other
      antigens from immune complexes in serum and plasma samples.
AB  - Accuracy of antigen determination in human plasma samples is often adversely
      affected by immune complex formation between antigens (e.g., HIV-1 p24 protein)
      and specific antibodies. In this study we describe an optimized method for
      complete immune complex dissociation (ICD) in plasma. This method is based on
      heat denaturation of antibodies and utilizes a defined solution of sodium dodecyl
      sulfate (SDS) and diethylenetriaminepentaacetic acid (DTPA) as diluent. The
      efficiency of this procedure for ICD was compared with those of published
      methods, employing heat denaturation alone and acidification. Plasma samples from
      patients participating in anti-retroviral treatments and samples reconstituted in
      vitro were treated and analyzed in parallel. HIV-1 p24 antigen was determined by
      quantitative enzyme-linked immunosorbent assay (ELISA). In 312 samples from 97
      patients, antigenemia was found in 44.9% when measured directly and in 87.2%
      after this treatment. In a subset of 56 samples, 21.4% tested positive prior to
      treatment, while after either novel treatment, heat denaturation or
      acidification, these samples tested positive in 80.4%, 62.5% and 60.7%,
      respectively. In 94% of cases viral RNA was detected. This improved procedure for
      ICD provides a reliable and convenient method for complete and accurate p24
      antigen detection in human plasma and is applicable to commercially available
      test kits.

PMID- 9776585
TI  - A comparative study of different methods for the assessment of apoptosis and
      necrosis in human eosinophils.
AB  - Eosinophils, prominent cells in asthmatic inflammation, undergo apoptosis or
      programmed cell death following deprivation of contact with survival-promoting
      cytokines such as IL-5 and GM-CSF. The aim of this study was to assess a number
      of techniques for the quantification of apoptosis in human eosinophils cultured
      with or without IL-5 or GM-CSF and following staurosporine treatment. The
      relationship between apoptosis and necrosis in eosinophils was also determined.
      Eosinophils 'aged' in vitro for 48 h exhibited endonuclease DNA degradation,
      apoptotic morphology, increased red autofluorescence and externalisation of
      phosphatidylserine (PS) as assessed by binding of FITC-labelled annexin V.
      Annexin V-FITC binding was first detectable in eosinophils maintained at 37
      degrees C for 5 h post-purification. This method proved to be the most sensitive
      marker of apoptosis. Morphological assessment of wet preparations of eosinophils
      by Kimura staining was found to be the next most-sensitive marker followed by
      increased red autofluorescence. The latter was a relatively insensitive method
      for the detection of apoptosis. At 5, 20 and 24 h of culture trypan blue
      exclusion indicated that eosinophil viability was high (85-90% viable cells).
      However, propidium iodide (PI) staining and flow cytometry revealed that, by 24
      h, approximately 75% of cells had compromised membrane integrity. Eosinophils
      maintained in IL-5 or GM-CSF exhibited a non-apoptotic morphology and levels of
      annexin V-FITC binding and PI uptake similar to that of freshly isolated cells.
      Staurosporine (10(-5) M) treatment of eosinophils maintained in IL-5 or GM-CSF
      resulted in significant levels of apoptotic morphology at 2 h (23.8% +/- 6.9, p <
      0.025) which was associated with negligible annexin binding. At 6 h post
      staurosporine treatment significant annexin-FITC binding (38% +/- 1.5, p < 0.025)
      was observed compared with 93% +/- 1.2 of eosinophils displaying apoptotic
      morphology. Exclusion of PI demonstrated membrane integrity at all time points up
      to 6 h. Thus, eosinophils aged in vitro in the absence of viability-promoting
      cytokines exhibit evidence of both apoptosis and necrosis simultaneously. In
      contrast, staurosporine-treated eosinophils exhibited both membrane integrity and
      rapid apoptosis-associated morphological changes detected by single step Kimura
      staining which preceded externalisation of PS.

PMID- 9776586
TI  - Optimization and comparison of the MTT assay and the 3H-TdR assay for the
      detection of IL-2 in helper T cell precursor assays.
AB  - The helper T cell precursor (HTLp) assay is of value for predicting graft-versus
      host disease after allogeneic bone marrow transplantation. The assay requires
      reliable detection of the amount of interleukin 2 (IL-2) produced by one cell. To
      optimize the IL-2 sensitivity of our HTLp assay we tested an IL-2 dependent cell
      line, CTLL-2, with two different measurement methods: a colorimetric assay with
      tetrazolium (MTT) and an isotope incorporation assay with 3H-thymidine (3H-TdR).
      The test conditions examined encompassed: time without IL-2, preincubation time
      in IL-2, CTLL-2 cell concentration and different human sera. Due to the different
      measurement procedures, the volumes of the IL-2 dilutions were 75 microl in
      assays with MTT and 150 microl in assays with 3H-TdR. We found that it was the
      amount of IL-2, not the concentration, that limited the growth of CTLL-2 cells.
      In the most optimal setting the MTT assay could detect 0.6 pg IL-2/well,
      corresponding to 8 pg/ml. For the 3H-TdR assay the sensitivity was 0.6 pg/well,
      corresponding to 4 pg/ml. Because of the possibility of IL-2 detection in the
      whole culture volume (150 microl), we found that the 3H-TdR assay was superior to
      the MTT assay with a 10-fold better sensitivity in different human sera.

PMID- 9776587
TI  - A highly sensitive whole blood natural killer cell assay.
AB  - The assessment of natural killer cell activity at baseline and the monitoring of
      this activity during treatment is important in many diseases especially in
      patients with cancer and AIDS. An optimised and standardised whole blood chromium
      release assay is described using K562 cells, the standard target erythroleukaemic
      cell line. The tumour cell lysis observed using whole blood is comparable to that
      obtained with the standard 4 h lysis assay using peripheral blood mononuclear
      cells as effector cells. Results with the whole blood assay are reproducible when
      the incubation with K562 cells is performed over a period of 18 h. The assay
      necessitates only 0.6 ml of blood collected in 10 IU/ml of sodium heparin as the
      anticoagulant. In this report, depletion experiments, also standardised using
      whole blood, show that the effector cells in the whole blood assay are contained
      within the CD56 + cell population. This assay will be of interest where the
      immunological status of patients with different diseases need to be frequently
      monitored.

PMID- 9776588
TI  - Comparison of detection techniques for cytokine reverse transcriptase polymerase
      chain reaction; digoxigenin-labeled polymerase chain reaction permits sensitive
      detection of cytokine mRNA in rat heart allografts.
AB  - The polymerase chain reaction (PCR) is a sensitive method for the analysis of
      cytokine mRNA expression. The amount of specific mRNA in tissues involved in an
      inflammatory immune response can be low and therefore requires highly sensitive
      detection of the PCR products. In our study we have compared different detection
      techniques in order to replace the commonly used detection by means of
      radiolabeled probes. Besides the detection of DNA in agarose gels by ethidium
      bromide (EB), we used detection by digoxigenin (DIG)-labeled probes, as well as
      the direct incorporation of DIG-labeled nucleotides in the PCR, in comparison to
      detection by means of 32P-labeled probes. In vitro activated rat lymph node
      cells, lymph node tissue, and acutely or chronically rejected rat heart
      allografts were examined for expression of mRNA of the cytokines IL-2 and
      IFNgamma. The directly DIG-labeled PCR appeared to be the best alternative for
      detection of PCR products by means of radiolabeled probes. While IL-2 mRNA was
      not detected by means of EB and IFNgamma mRNA was only detected at the highest
      PCR cycle numbers in acutely and chronically rejected rat heart allografts, both
      cytokine mRNA's were readily detected by directly DIG-labeled PCR.

PMID- 9776589
TI  - A vector for the expression of recombinant monoclonal Fab fragments in bacteria.
AB  - The availability of genes coding for monoclonal Fab fragments of a desired
      specificity permits their expression in bacteria and provides a simple method for
      the generation of good quality reagents. In this paper we describe a new phagemid
      vector for the production of recombinant Fabs from genes obtained from phage
      display combinatorial libraries. The phagemid features an antibiotic resistance
      cassette which, once inserted between the heavy chain fragment and the light
      chain genes, avoids unwanted recombination and preserves useful restriction sites
      not affecting the Fab production rate.

PMID- 9776591
TI  - Severe male infertility. Impact of genetic factors on diagnosis and counselling.

PMID- 9776590
TI  - Are the new microfertilization techniques associated with an increased genetic
      risk to the offspring?

PMID- 9776592
TI  - Can a single measurement of amniotic fluid delta optical density be safely used
      in the clinical management of Rhesus-alloimmunized pregnancies before 27 weeks'
      gestation?
AB  - BACKGROUND: To assess the efficacy of a single measurement of amniotic fluid
      optical density deviation at 450 nanometers in predicting fetal anemia in Rhesus
      alloimmunization before 27 weeks gestation. METHODS: In this cross-sectional
      study, fetal blood and amniotic fluid samples from 43 Rhesus-alloimmunized
      pregnancies at 18 to 26 weeks gestation were obtained under ultrasound guidance.
      Amniotic fluid samples were scanned by spectrophotometry for optic density at
      various wavelengths. Deviation at 450 nanometers was calculated between 550 and
      365 nanometers. The fetuses were divided into three groups based on their
      hematocrit levels and the predictive efficacy of optic density zones for anemia
      was evaluated. RESULTS: A high number of false positive and false negative
      results were observed when the delta-amniotic fluid optical density of fetuses at
      risk for anemia was plotted to the zones recently proposed to manage Rhesus
      alloimmunized pregnancies. CONCLUSIONS: These data confirm previous results that
      the diagnosis of fetal anemia in Rhesus-alloimmunized pregnancies before 27
      weeks' gestation cannot be accurately made by a single measurement of amniotic
      fluid optical density at 450 nanometers.

PMID- 9776593
TI  - Increased circulating concentrations of asymmetric dimethyl arginine (ADMA), an
      endogenous inhibitor of nitric oxide synthesis, in preeclampsia.
AB  - OBJECTIVES: To study endogenous nitric oxide (NO) synthesis inhibitors in
      preeclampsia by measuring asymmetric dimethyl arginine (ADMA) and arginine. STUDY
      DESIGN: Blood samples for measurement of plasma concentrations of ADMA and
      arginine were obtained antepartum (range 32-39 weeks gestation), 3-5 days
      postpartum and 3 months postpartum from 12 pregnant women with severe
      preeclampsia and from a normotensive pregnant control group (n=12). RESULTS:
      During the third trimester, plasma ADMA was elevated (p<0.05) in the preeclampsia
      patients (0.55+/-0.02 micromol/l) compared to the normotensive pregnant controls
      (0.36+/-0.01 micromol/l). Since plasma arginine levels did not differ between
      preeclamptic and normotensive control women (80.7+/-5.8 micromol/l) and 74.5+/
      3.8 micromol/l respectively), the plasma arginine/ADMA ratio was lower (p<0.05)
      in the preeclamptic group (145.6+/-10.5) compared to the normotensive controls
      (211.0+/-14.3). Three days post partum there was an increase (p<0.05) in plasma
      ADMA in both the preeclamptic (0.67+/-0.03 micromol/l) and the normotensive
      control group (0.64+/-0.03 micromol/l). This was accompanied by a rise (p<0.05)
      in plasma arginine levels in both the preeclamptic patients (112.9+/-10.5
      micromol/l) and the normotensive control group (121.7+/-9.6 micromol/l). At this
      time point there was no difference in plasma arginine/ADMA ratio between the
      groups. Three months postpartum, plasma ADMA levels were slightly lower in both
      groups compared to the postpartum values (preeclampsia: 0.56+/-0.03 micromol/l,
      normotensive pregnant control: 0.52+/-0.03 micromol/l). CONCLUSION: Elevated
      circulating ADMA concentrations in combination with low plasma arginine levels
      may be of pathophysiological importance in pregnancies complicated with
      preeclampsia.

PMID- 9776594
TI  - Pregnancies complicated by diabetic proliferative retinopathy.
AB  - BACKGROUND: To examine retinal and pregnancy outcome in insulin-dependent
      diabetic women with proliferative retinopathy and assess the effect of
      albuminuria on morbidity. METHODS: The records of 26 women with known
      proliferative retinopathy before pregnancy were studied retrospectively in the
      prepregnancy period, during pregnancy, and after delivery. Perinatal and maternal
      morbidity was studied using ophthalmic, obstetric and pediatric records. RESULTS:
      Seven pregnancies were delivered preterm (27%). Serious neonatal morbidity
      occurred in five pregnancies (19%). Perinatal survival was 88%. Laser treatment
      was given prior to pregnancy to 54%, during pregnancy to 27% and after delivery
      to 31% of the women. Laser treatment during pregnancy was more common in those
      with no prior photocoagulation and in White class F/R. Low birthweight was more
      frequently associated with nephropathy and proliferative retinopathy compared to
      retinopathy alone (p<0.05). Recent hemorrhage, maculopathy or glaucoma was found
      in 14 (54%) of the women. Blindness developed unilaterally in two women.
      CONCLUSIONS: Perinatal morbidity was associated with nephropathy rather than
      retinopathy. The incidence of hemorrhage, maculopathy or glaucoma was similar in
      White classes R and F/R.

PMID- 9776595
TI  - Fear of childbirth and psychosomatic support. A follow up of 72 women.
AB  - BACKGROUND: Women with severe anxiety of childbirth need special support. AIMS:
      To follow up women who had received individualized psychological/obstetric
      support because of anxiety of delivery and to describe this model of support.
      METHODS: Questionnaires were sent to 100 women who had suffered from anxiety of
      delivery and to 100 matched references; 72 pairs provided answers. RESULTS: Some
      women in the study group (25%) accepted psychotherapy during the pregnancy, and
      the others a modified support. In comparison with the references they remembered
      the pregnancy as a less positive experience (p=0.02), less vigor (p=0.002), less
      psychic well-being (p=0.04), more worry about health (p=0.04), more need for
      encouragement (p=0.001) and less emotional preparedness for delivery (p=0.01).
      Their experiences of delivery were similar as the references' and in some
      respects even more positive. The women who initially had wished a cesarean
      section but eventually underwent a vaginal delivery were as satisfied as those
      who had not wished a cesarean section. The women recommended the staff to take
      women's worry seriously (study and reference group 64% and 26% respectively, p
      value 0.003) and to build up trust and give support (30% and 19% respectively, p
      value 0.003). CONCLUSION: Women with fear of childbirth remembered the pregnancy
      as distressing, in spite of support. They remembered the delivery similarly as
      references, also those who initially had asked for a cesarean section but
      eventually underwent a vaginal delivery.

PMID- 9776596
TI  - Socio-demographic risk factors for perinatal mortality. A study of perinatal
      mortality in the French district of Seine-Saint-Denis.
AB  - OBJECTIVES: To investigate the impact of a set of socio-demographic risk factors
      commonly associated with perinatal mortality -- age, parity, marital status,
      educational attainment, occupation, and ethnic origin in the French district of
      Seine-Saint-Denis. METHODS: The study has a case-control design with prospective
      identification of cases. It includes all singleton non-malformed perinatal deaths
      which occurred between October 1, 1989 and September 30, 1992. Logistic
      regression is used to estimate odds ratios. Base incidence rates are generated by
      incorporating sampling information for the controls. RESULTS: All socio
      demographic variables are significantly related to the risk of perinatal
      mortality in univariate analyses. Some of the increased risk due to social
      factors is explained by differential age and parity distributions. In
      multivariate models, however, only parity and country of origin are significant.
      Women born in the French overseas departments and territories and Sub-Saharan
      Africa have the highest odds ratios. CONCLUSIONS: Women born outside of
      continental France face an elevated risk of experiencing a perinatal death even
      after controlling for age, parity and socioeconomic factors. Although, this
      excess risk may reflect residual variation in socioeconomic status, alternative
      explanations such as standards of prenatal care, medical problems during
      pregnancy and delivery, and cultural practices should be explored.

PMID- 9776597
TI  - Smoking habits among Danish pregnant women from 1989 to 1996 in relation to
      sociodemographic and lifestyle factors.
AB  - BACKGROUND: The aim of the study was to describe changes in smoking habits among
      Danish pregnant women during an eight-year period in relation to changes in
      sociodemographic and lifestyle factors. METHODS: From 1989 to 1996 all pregnant
      women attending routine antenatal care at the Department of Gynecology and
      Obstetrics at Aarhus University Hospital who completed an inclusion questionnaire
      were invited to participate in the present study (n=27,194). They were asked to
      complete two additional questionnaires during pregnancy. Apart from smoking
      habits. these questionnaires provided information on medical and obstetric
      history together with information on sociodemographic and other lifestyle
      variables. RESULTS: The proportion of pregnant smokers decreased from 34% (95%
      CI: 32%/36%) in 1989 to 21% (95% CI: 19%-22%) in 1996 (p<0.001). The mean number
      of cigarettes per day remained almost constant during the study period.
      Stratified and multivariate analyses showed that the results were not confounded
      by changes in sociodemographic and lifestyle factors. CONCLUSIONS: From 1989 to
      1996 a significant reduction in the proportion of pregnant smokers was found.
      There were no specific campaigns against smoking in pregnancy during this period
      and the reduction was not associated with changes in sociodemographic and
      lifestyle factors.

PMID- 9776598
TI  - The effect of labor on the acid-base status of the newborn.
AB  - BACKGROUND: There has been some controversy regarding the effect that a long
      labor can have on fetal well-being. This study was undertaken to evaluate the
      effect of duration of labor both the first and second stage on the acid-base
      variables in the umbilical artery of the newborn. METHODS: Bloodsampling was
      attempted from all infants born at our department between October 1994 and
      September 1995. Nineteen hundred and forty-one live infants were delivered during
      the period. Sampling was unsuccessful in 264 cases and after excluding infants
      with operative delivery, multiple gestations, breech presentation, prematurity,
      postmaturity and infants small for gestational age 1255 remained singleton, term
      infants with vertex presentation and non-operative vaginal birth. RESULTS: We
      found no correlation between duration of the first stage of labor and neither pH
      nor base excess in umbilical artery blood. There was a significant correlation
      between duration of the second stage of labor and both the pH and base excess.
      For vaginal nulliparas we found that pH=7.30-0.016 x second stage duration in
      hours and base excess=-3.71-0.692 x second stage duration in hours. For women
      with previous vaginal births pH=7.31-0.029 x second stage duration in hours and
      base excess=-2.38-1.306 x second stage duration in hours. CONCLUSIONS: We find no
      correlation between duration of the first stage of labor and umbilical artery pH
      or base excess. We do find a correlation between duration of the second stage of
      labor and the umbilical artery pH and base excess. However, a prolongation of the
      second stage with as much as three hours would give an expected lowering of the
      umbilical artery pH with only 0.05 and of base excess with 2.1 mmol/l for vaginal
      nulliparas and correspondingly with 0.09 and 3.9 mmol/l in women with previous
      vaginal births. This effect on pH and base excess is so small that it is hardly
      clinically relevant and we do not find any support for the belief that a long
      labor -- in the absence of other risk factors -- is to the disadvantage of the
      fetus.

PMID- 9776599
TI  - Birth in triplet pregnancies. Vaginal delivery--how often is it possible?
AB  - OBJECTIVE: To compare cesarean section with vaginal delivery in triplet
      pregnancies. DESIGN: Medical records of 16 triplet pregnancies were
      retrospectively reviewed. SETTING: One hospital where planned, vaginal delivery
      of triplet gestations is the preferred policy. SUBJECTS: Sixteen women giving
      birth to triplets in the University Hospital, Uppsala, Sweden. RESULTS: Nine
      women were delivered vaginally, seven with cesarean section. The corrected
      mortality was 3.3% in the group delivered vaginally and zero in the cesarean
      section group. Twenty-three percent of the babies in the vaginally delivered
      group were without any morbidity and 6% in the corresponding cesarean section
      group. CONCLUSIONS: In terms of fetal outcome cesarean section in triplets is not
      superior to a policy of vaginal delivery. Vaginal delivery may be suggested when
      there are no obvious obstetrical contraindications.

PMID- 9776600
TI  - Obstetric outcome in patients with unexplained infertility: comparison of
      treatment-related and spontaneous pregnancies.
AB  - BACKGROUND: The aim of this study was to determine the long-term prognosis of
      fecundity among couples with unexplained infertility and to compare pregnancy
      course and outcome in spontaneous versus treatment-related pregnancies. METHODS:
      A prospective follow-up study of 70 couples with a diagnosis of unexplained
      infertility. All couples had participated in a study at the Helsinki University
      Central Hospital where the effectiveness was compared with intrauterine
      insemination, direct intraperitoneal insemination or timed intercourse, each
      combined with superovulation. The follow-up was carried out by collecting all
      available information on treatment-related and spontaneous pregnancies from
      hospital records and questionnaires mailed to these same women 6 years later.
      RESULTS: Of 70 couples, 45 (64.3%), conceived during the follow-up period. Of all
      83 pregnancies, 50 (60.2%) began spontaneously and 33 (39.8%) with infertility
      treatment. Rate of multiple deliveries was 25% in treatment-related pregnancies,
      but only 2.8% in spontaneous pregnancies (p<0.05). Mean birthweight among
      singleton pregnancies was 3 120 grams in treatment-related, and 3387 grams in
      spontaneous pregnancies (p<0.05). The rate of small-for-gestational-age (<-2
      s.d.) and preterm births (before 37 completed weeks) in both groups was equal.
      CONCLUSIONS: The long-term prognosis of couples with unexplained infertility was
      good, and many of the pregnancies began spontaneously. The birthweight of
      singleton neonates in treatment-related pregnancies was lower than in
      spontaneously conceived pregnancies, but otherwise perinatal outcome was similar.

PMID- 9776601
TI  - Comparison of buserelin and nafarelin in IVF cycles and in subsequent frozen
      thawed embryo transfer cycles.
AB  - OBJECTIVE: To compare two gonadotropin-releasing hormone agonists for down
      regulation prior to superovulation in in vitro fertilization/embryo transfer
      treatment. METHODS: Infertility patients (n=181) were randomized to receive
      buserelin (1200 microg/day, n=90) or nafarelin (800 microg/day, n=91)
      intranasally starting in the luteal phase. Serum levels of LH, estradiol and
      progesterone were measured during the treatment. The cycles were compared with
      regard to number of oocytes, fertilization and implantation rates and achieved
      pregnancies. RESULTS: Serum LH was lower after two weeks on buserelin: 1.8 (1.3
      2.4) IU/L (median, with lower and upper quartile in parenthesis), than after
      nafarelin: 2.6 (1.8-4.0) IU/L, (p=0.0001). No other differences in serum hormone
      levels could be detected. More oocytes were recovered in the buserelin group:
      13.0 (8.0-19.0) vs 11.0 (6.8-15.0), (p=0.046), but the fertilization rate was
      higher in the nafarelin group (49.9%, vs 45.1%, p=0.023). Implantation rate was
      higher in the nafarelin group (26.28% vs 15.5%, p=0.030), but there were an equal
      number of deliveries in both groups (20.9% vs 15.6% per started stimulation,
      p=0.420). In the subsequent frozen-thawed embryo transfer cycles the implantation
      rate was 21.1% (nafarelin group) and 10.6% (buserelin group, p=0.067), the
      pregnancy rate/ET was 31.7% and 17.0% (p=0.107) and the delivery rate was 22.0%
      and 10.6% (p=0.148), respectively. CONCLUSIONS: Differences exist in IVF-cycles
      down-regulated with buserelin or nafarelin which might affect embryo quality and
      treatment outcome.

PMID- 9776602
TI  - Color Doppler ultrasonography in the earlier differentiation of benign
      molehydatidiforms from malignant gestational trophoblastic disease.
AB  - BACKGROUND: To find out the effectiveness of color Doppler ultrasonography of the
      uterine arteries in the differentiation of benign molehydatidiforms from
      malignant gestational trophoblastic disease. METHODS: Prospective study was
      performed in 32 women who were referred to the Oncology Department with the
      diagnosis of gestational trophoblastic disease. Uterine artery Doppler studies
      were made and resistance index for both uterine arteries were calculated. In the
      follow-up, twelve of these patients required chemotherapy (first group) and 20 of
      them were treated with only suction curettage (second group). Non parametric Mann
      Whitney U test was used for the statistical analysis. RESULTS: Median of the
      lowest uterine artery resistance index were 0.29 for the first group and 0.46 for
      the second group. Resistance index were significantly lower in the first group
      (alpha<0.001). Color Doppler study of the uterine arteries is helpful in the
      differentiation of benign molehydatiforms from malignant gestational
      trophoblastic disease.

PMID- 9776603
TI  - Fluid absorption and the long-term outcome after transcervical resection of the
      endometrium.
AB  - BACKGROUND: Fluid absorption may cause symptoms of acute volume overload and has
      also been associated with a less favorable outcome after endometrial resection.
      To further study this topic, we evaluated the incidence of fluid absorption, the
      factors associated with absorption, and the relationship between fluid absorption
      and the long-term outcome after TCRE. METHOD: Two hunded and sixty-five women
      underwent TCRE in which the absorption of irrigating fluid (glycine 1.5%) was
      measured volumetrically. Physical examinations were made and questions about
      menstrual blood loss and cyclic pelvic pain were asked before the operation and
      12 weeks and 1, 2, and 3 years later. RESULTS: Fluid absorption was increased in
      patients treated with a GnRH analogue (leuprolide acetate) prior to the TCRE
      (p<0.007) and also when a submucous myoma was removed during the operation
      (p<0.0001). About 40% of the women operated on still had menstrual bleeds 1 year
      later, and this correlated with a larger fluid absorption (p<0.04). Dysmenorrhea
      disappeared in half the patients, while 17% of those who were pain-free before
      the TCRE had developed cyclic pelvic pain at 1 year, an outcome also associated
      with a larger fluid absorption (p<0.02). Pain correlated with lower patient
      satisfaction, preserved menstrual bleeds, and with the presence of remnants of
      endometrial tissue as imaged by transvaginal ultrasonography. CONCLUSIONS:
      Resection of a submucous adenoma increases the risk of fluid absorption during
      TCRE. The results also indicate that fluid absorption is associated with
      persistent menstrual bleeding and late development of cyclic pelvic pain.

PMID- 9776604
TI  - Interferon alpha-2a therapy and pregnancy. Report of a case of chronic
      inflammatory demyelinating polyneuropathy.

PMID- 9776606
TI  - Endometrial strongyloides stercoralis in a healthy woman.

PMID- 9776605
TI  - Psammocarcinoma of the peritoneum diagnosed during operative laparoscopy.

PMID- 9776607
TI  - Diffuse laminar endocervical hyperplasia (DLEGH) or Chlamydia trachomatis
      infection?

PMID- 9776609
TI  - Medical students' attitudes toward, knowledge of, and experience with
      complementary medicine therapies.

PMID- 9776608
TI  - Is admission test in labor justified in low-risk women?

PMID- 9776610
TI  - Selected papers from the 53rd annual meeting of the American Society for
      Reproductive Medicine. Cincinnati, Ohio, USA. October 18-22, 1997.

PMID- 9776611
TI  - Current Concepts and Controversies in Vital Pulp Capping. Proceedings of a
      Symposium. Orlando, Florida, March 16, 1997.

PMID- 9776612
TI  - Microgravity and its implication for fermentation biotechnology.
AB  - Fermentation processes are highly dependent upon physical and chemical
      environmental parameters, many of which are influenced by gravity. Extending
      biotechnology into the realm of space flight provides researchers with an
      opportunity to investigate the role that gravity plays in natural growth
      processes. Physical factors governing cell sedimentation, nutrient mixing and
      byproduct dispersion are altered in the absence of the constant sedimenting force
      of gravity. In addition, space flight has also been shown to give rise to a wide
      variety of indirect consequences associated with the physiology of the organisms
      themselves.

PMID- 9776613
TI  - Proposal to amend rule 61 of the International Code of Nomenclature of Bacteria
      (1990 revision).
AB  - It is proposed to modify the Note of rule 61 as follows: 'The liberty of
      correcting a name or epithet under Rules 61, 62a and 62b must be used with
      reserve especially i) if the change affects the first syllable and above all the
      first letter of the name or epithet, and ii) if a name or epithet is cited in the
      Approved Lists of Bacterial Names.'

PMID- 9776614
TI  - Necessary corrections according to judicial opinions 16, 48 and 52.

PMID- 9776615
TI  - Validation of the publication of new names and new combinations previously
      effectively published outside the IJSB. List No. 65.

PMID- 9776616
TI  - Symposium on inflammatory and immune mechanisms in vascular disease. Bethesda,
      Maryland, USA. February 19-20, 1998. Abstracts.

PMID- 9776617
TI  - Active measurements of indoor concentrations of radon and thoron gas using
      charcoal canisters.
AB  - Standardized charcoal canisters with diameters of 4 inch, of a type recommended
      by the USEPA for passive measurement of radon gas concentrations, have been
      modified for active air sampling. Simultaneous measurement of the concentrations
      of radon (Rn) and thoron (Tn) in air can be obtained by counting the areas under
      gamma-ray peaks. Sample results obtained in a laboratory and in a residence with
      different conditions are also given. The largest uncertainties are about 2% and
      3% for Rn and Tn respectively. The minimum detection limits are around 2.0 Bq/m3
      for both gases. If only Rn concentration is required, the measurement time can be
      significantly shortened.

PMID- 9776618
TI  - Natural and man-made radioactivity in soils and plants around the research
      reactor of Inshass.
AB  - The specific radioactivities of the U-series, 232Th, 137Cs and 40K were measured
      in soil samples around the Inshass reactor in Cairo, using a gamma-ray
      spectrometer with a HpGe detector. The alpha activity of 238U, 234U and 235U was
      measured in the same soil samples by surface barrier detectors after
      radiochemical separation and the obtained results were compared with the specific
      activities determined by gamma-measurements. The alpha-activity of 238Pu,
      239+240Pu, 241Am, 242Cm and 244Cm was measured after radiochemical separation by
      surface barrier detectors for both soil and plant samples. Then beta-activity of
      241Pu was measured using liquid scintillation spectrometry.

PMID- 9776619
TI  - Appendix: foreign proteins expressed in P. pastoris.

PMID- 9776620
TI  - Proceedings of the 17th International Symposium on the Separation and Analysis of
      Proteins, Peptides and Polynucleotides. Washington, DC, USA. 26-29 October 1997.

PMID- 9776622
TI  - [Symptom of acute cholecystitis in obese patients].

PMID- 9776623
TI  - The history of psychiatry in Hradec Kralove.

PMID- 9776624
TI  - Cardioaortic and aortic surgery: has surgical art progressed in fifty years?

PMID- 9776625
TI  - Aortic root replacement in patients with Marfan's syndrome and annulo-aortic
      ectasia. How and when?

PMID- 9776626
TI  - Current strategies of the Fontan operation.

PMID- 9776627
TI  - [The AETS (Agencia de Evaluacion de Tecnologias Sanitarias) report on PET in
      clinical oncology].

PMID- 9776628
TI  - Surgically responsive focal tremor associated with a frontal convexity
      meningioma.

PMID- 9776629
TI  - Application of bilateral sequential pallidotomy to treat a patient with
      generalized dystonia.

PMID- 9776630
TI  - A myasthenic syndrome associated with combined autoantibodies to postsynaptic
      acetylcholine receptors and presynaptic voltage-gated calcium channels.

PMID- 9776631
TI  - Incidence of cerebrovascular insult in Split.

PMID- 9776632
TI  - Meningitis and myelitis by Mycobacterium bovis resistant to isoniazid.

PMID- 9776633
TI  - Guillain-Barre syndrome in association with focal segmental glomerulosclerosis.

PMID- 9776634
TI  - Enhanced penicillin production by oligosaccharides from batch cultures of
      Penicillium chrysogenum in stirred-tank reactors.
AB  - Alginate and galactomannan-derived oligosaccharides enhanced the production of
      penicillin G when added to stirred tank reactor cultures of Penicillium
      chrysogenum. The addition of oligomannuronate and oligoguluronate blocks
      increased penicillin G yield by 47% and 49%, respectively. The effect of mannan
      oligosaccharides was found to be more pronounced with 69% higher yield than the
      control cultures. The maximum increase in the average specific productivity of
      the oligosaccharide augmented cultures was 55% after addition of mannan
      oligosaccharides. In addition, a difference was observed in all cases in the
      accumulation pattern of the intermediate of penicillin biosynthesis, delta-(L
      alpha-aminoadipyl)-L-cysteinyl-D-valine.

PMID- 9776635
TI  - Characterization of an Aspergillus nidulans mutant with abnormal distribution of
      nuclei in hyphae, metulae, phialides and conidia.
AB  - The V10 deteriorated variant of Aspergillus nidulans has hyphae, metulae,
      phialides and conidia with abnormal nuclear distributions. The alterations
      observed were: increase in the number of nuclei in hyphae, metulae and phialides,
      presence of anucleate, uninucleate and multinucleate conidia, abnormal vegetative
      growth and defection conidiation. When 0.5 M NaCl was added to the medium, an
      increase in the number of conidia was observed but their morphology and number of
      nuclei were not modified. The gene responsible for these alterations was named
      anuA1. The anuA1 gene is located on linkage group VII and is possibly involved in
      nuclear migration to hyphae, metulae, phialides and conidia.

PMID- 9776636
TI  - 52nd annual fall conference of the Council for High Blood Pressure Research.
      Philadelphia, Pennsylvania, USA. September 15-18, 1998. Abstracts.

PMID- 9776637
TI  - Proceedings of the 40th Congress of the International Psychoanalytical
      Association. Barcelona, 1997.

PMID- 9776638
TI  - Consensus Conference on Open or Closed Management of Condylar Fractures. 12th
      ICOMS. Budapest, 1995.

PMID- 9776639
TI  - Directory. Prosthetic dentistry.

PMID- 9776640
TI  - Graft rescue for haemodialysis arterio-venous grafts: is it worth doing and which
      factors predict a good outcome?
AB  - Arterio-venous grafts in patients with end-stage renal failure are used when the
      patients have inadequate native veins or where there is an urgent need for
      permanent vascular access. Complications include thrombosis, bleeding, infection
      and pseudoaneurysm formation. The factors causing thrombosis can be divided into
      patient-related and graft-related factors. In this study 47 graft rescues in 24
      patients were analysed. Polytetrafluoroethylene (PTFE) and polyurethane grafts
      were used. A successful graft rescue was defined as one in which a thrill was
      felt after surgical thrombectomy and the graft was subsequently used for
      haemodialysis. Eighteen grafts were PTFE and 10 were polyurethane; there were 15
      women and nine men. There were 20 successful and 27 unsuccessful rescues, the
      overall success rate being 42.6% (20/47 rescues). Evidence of underlying stenoses
      was found in 14 graft rescues: 11 were at the venous end, two at the arterial end
      and one at the apex. A vein patch was used in these patients. In successful graft
      rescues an identifiable structural cause was found in only seven (25.9%) of the
      failed graft rescues. In spite of the common belief that graft rescue is
      unproductive, this study has shown that graft rescue was successful in 42.6% of
      cases. This was especially so when there was a surgically correctable underlying
      graft stenosis.

PMID- 9776641
TI  - Candesartan cilexetil vs losartan.

PMID- 9776642
TI  - Dental practice in a changing marketplace.

PMID- 9776643
TI  - [The 3rd Japanese-United States Vancomycin Forum].

PMID- 9776644
TI  - Proposition: medical technologies should pass performance and cost-effectiveness
      review in centers of excellence before being released for diffusion in the
      clinical community.

PMID- 9776645
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 31-1998. An eight-year-old boy with bronchiectasis.

PMID- 9776646
TI  - Prolongation of the QT interval and the sudden infant death syndrome.

PMID- 9776647
TI  - Prolongation of the QT interval and the sudden infant death syndrome.

PMID- 9776648
TI  - Prolongation of the QT interval and the sudden infant death syndrome.

PMID- 9776649
TI  - Prolongation of the QT interval and the sudden infant death syndrome.

PMID- 9776650
TI  - Prolongation of the QT interval and the sudden infant death syndrome.

PMID- 9776651
TI  - Tirofiban in unstable coronary disease.

PMID- 9776652
TI  - Cardiac response to enzyme-replacement therapy in Gaucher's disease.

PMID- 9776653
TI  - Hospitalizations and the homeless.

PMID- 9776654
TI  - Hospitalizations and the homeless.

PMID- 9776655
TI  - Hospitalizations and the homeless.

PMID- 9776656
TI  - Effects of daylight savings time on collision rates.

PMID- 9776657
TI  - Proceedings of the 5th Symposium on Food Proteins: Structural and Functional
      Aspects of Protein Modification. Potsdam, Germany, 1-3 September 1997.

PMID- 9776658
TI  - Combined chemoreduction and adjuvant treatment for intraocular retinoblastoma.

PMID- 9776659
TI  - Biomarkers as tracers for life on early earth and Mars.
AB  - Biomarkers in geological samples are products derived from biochemical (natural
      product) precursors by reductive and oxidative processes (e.g., cholestanes from
      cholesterol). Generally, lipids, pigments and biomembranes are preserved best
      over longer geological times and labile compounds such as amino acids, sugars,
      etc. are useful biomarkers for recent times. Thus, the detailed characterization
      of biomarker compositions permits the assessment of the major contributing
      species of extinct and/or extant life. In the case of the early Earth, work has
      progressed to elucidate molecular structure and carbon isotropic signals
      preserved in ancient sedimentary rocks. In addition, the combination of bacterial
      biochemistry with the organic geochemistry of contemporary and ancient
      hydrothermal ecosystems permits the modeling of the nature, behavior and
      preservation potential of primitive microbial communities. This approach uses
      combined molecular and isotopic analyses to characterize lipids produced by
      cultured bacteria (representative of ancient strains) and to test a variety of
      culture conditions which affect their biosynthesis. On considering Mars, the
      biomarkers from lipids and biopolymers would be expected to be preserved best if
      life flourished there during its early history (3.5-4 x 10(9) yr ago). Both
      oxidized and reduced products would be expected. This is based on the inferred
      occurrence of hydrothermal activity during that time with the concomitant
      preservation of biochemically-derived organic matter. Both known biomarkers
      (i.e., as elucidated for early terrestrial samples and for primitive terrestrial
      microbiota) and novel, potentially unknown compounds should be characterized.

PMID- 9776660
TI  - Functional phylogeny: the use of the sensitivity of ribosomes to protein
      synthesis inhibitors as a tool to study the evolution of organisms.
AB  - In order to study the functional phylogeny of organisms, forty different protein
      synthesis inhibitors with diverse domain and functional specificities have been
      used to analyze forty archaeal, bacterial and eukaryotic translational systems.
      The inhibition curves generated with the different ribosome-antibiotic pairs have
      shown very interesting similarities among organisms belonging to the same
      phylogenetic group, confirming the feasibility of using such information in the
      development of evolutionary studies. A new method to extract most of the
      information contained in the inhibition curves is presented. Using a statistical
      treatment based on the principal components analysis of the data, we have defined
      coordinates for the organisms which have allowed us to perform a functional
      clustering of them. The phenograms obtained are very similar to those generated
      by 16/18S rRNA sequence comparison. These results prove the phylogenetic value of
      our functional analysis and suggest an interesting intersection between genotypic
      and phenotypic (functional) information.

PMID- 9776661
TI  - [The "mysterious" role of the clothes louse and its exposure (Charles Nicolle)].

PMID- 9776662
TI  - Influence of genuine kavapyrone enantiomers on the GABA-A binding site.
AB  - The influence of kavapyrones from Piper methysticum Forst. on the GABAA receptor
      was demonstrated using radioreceptor assays. Both the dienolide yangonin and the
      genuine enolide enantiomers (+)-kavain, (+)-dihydrokavain, (+)-methysticin, and
      (+)-dihydromethysticin enhanced the specific binding of [3H]bicuculline
      methochloride ([3H]BMC). The kavapyrones have been investigated at assay
      concentrations between 100 microM and 10 nM. (+)-Kavain, (+)-methysticin and (+)
      dihydromethysticin showed maximal enhancements of 18% to 28% at a concentration
      of 0.1 microM, whereas a 100-fold concentration of (+)-dihydrokavain revealed a
      similar modulatory activity of 22%. In the presence of 1 microM yangonin an
      increase of about 21% of the specific [3H]BMC binding was observed.
      Desmethoxyyangonin did not alter the binding behavior of the GABAA-receptor. A
      structure comparison of desmethoxyyangonin and yangonin indicated that the
      aromatic methoxy group was of particular importance for the modulatory activity.
      In contrast, the substitution pattern of the aromatic ring did not influence the
      modulatory activity of the enolides in a decisive manner. A structure comparison
      of desmethoxyyangonin and (+)-kavain revealed that an angular lactone ring was an
      important structure requirement. Both the enolides and the dienolides did not
      inhibit the specific binding of [3H]flunitrazepan. Thus, the influence on the
      GABAA receptor was not based upon an interaction of these kavapyrones with the
      benzodiazepine receptor.

PMID- 9776663
TI  - Determination of the components in a Chinese prescription, yu-ping-feng san, by
      RAPD analysis.
AB  - In this study, the RAPD (random amplified polymorphic DNA) technique was employed
      for the first time to determine the components in a Chinese herbal prescription.
      Forty decamer oligonucleotide primers were screened in the RAPD analysis to
      identify three Chinese medicines, the dried root of Astragalus membranaceus
      (Fisch.) Bge., the dried root of Ledebouriella seseloides Wolff, and the dried
      rhizome of Atractylodes macrocephala Koidz, in a Chinese prescription. Only
      primer OPP-10 simultaneously generated three distinct markers were each specific
      to one component. The marker with 200 bp is specific to Astragalus membranaceus;
      the 440 bp marker is specific to Atractylodes macrocephala; and the remaining
      marker with 500 bp was present in Ledebouriella seseloides. The presence of the
      three herbal medicines in the mixed sample, the Chinese prescription, was
      determined when the primer OPP-10 RAPD reaction was performed. The technique was
      proved to contribute to the identification of components in the Chinese medicinal
      preparations.

PMID- 9776665
TI  - [Congresses].

PMID- 9776664
TI  - Benzodiazepine binding site-interactive flavones from Scutellaria baicalensis
      root.
AB  - A benzodiazepine binding assay directed separation led to the identification of 3
      flavones baicalein (1), oroxylin A (2), and skullcapflavone II (3) from the water
      extract of Scutellaria baicalensis root. Compounds 1, 2, and 3 interacted with
      the benzodiazepine binding site of GABAA receptors with a Ki value of 13.1, 14.6
      and 0.36 micromol/L, respectively.

PMID- 9776666
TI  - [The debate on continuing education].

PMID- 9776667
TI  - [The dental operation].

PMID- 9776668
TI  - [Oral surgery and traumatology in the dental office. The SSO congress at Davos of
      June 11 to 13, 1998. Societe Suisse d'Odonto-Stomatologie].

PMID- 9776669
TI  - [Observations on health before and after amalgam removal].

PMID- 9776670
TI  - [Integrated quality].

PMID- 9776671
TI  - [Materials science--a pillar of dentistry. The 3rd Basel Materials Science
      Symposium of 5/6 December 1997].

PMID- 9776672
TI  - NIH to produce a 'working draft' of the genome by 2001.

PMID- 9776673
TI  - Animal experimentation. Strict rules rile Indian scientists.

PMID- 9776674
TI  - A record grant for college programs.

PMID- 9776675
TI  - China sets rules for foreign collaboration.

PMID- 9776676
TI  - Taming MEDLINE with concept spaces.

PMID- 9776677
TI  - A closer look at SNPs suggests difficulties.

PMID- 9776678
TI  - More SNPs on the way.

PMID- 9776679
TI  - A sweet way to keep proteins safe.

PMID- 9776680
TI  - Patent income.

PMID- 9776681
TI  - Solution to a conservation problem?

PMID- 9776682
TI  - Tobacco: who pays whom?

PMID- 9776683
TI  - Tobacco: who pays whom?

PMID- 9776684
TI  - The Swiss vote on gene technology.

PMID- 9776685
TI  - Telomeres--unsticky ends.

PMID- 9776686
TI  - Genetic variation as a guide to drug development.

PMID- 9776687
TI  - Two-hybridzyme.

PMID- 9776688
TI  - Metastasis in eggs.

PMID- 9776689
TI  - 26th Conference of the European Teratology Society. Stockholm, Sweden, 30 August
      2 September 1998. Abstracts.

PMID- 9776690
TI  - Proceedings of the Gastrointestinal Disorders in Juveniles Symposium. Lelystad,15
      16 September 1997.

PMID- 9776692
TI  - Annual scientific meeting of the Australian and New Zealand Society of Nuclear
      Medicine. Melbourne, Victoria, 4-8 April 1998. Abstracts.

PMID- 9776691
TI  - Ridiculitis: more [sic] humor.

PMID- 9776706
TI  - T-cell responses to myelin antigens in multiple sclerosis; relevance of the
      predominant autoimmune reactivity to myelin oligodendrocyte glycoprotein.
AB  - Until recently, the search for the 'culprit' autoantigen towards which
      deleterious autoimmunity is directed in multiple sclerosis (MS) centered mostly
      on myelin basic protein (MBP) and proteolipid (PLP), the two most abundant
      protein components of central nervous system (CNS) myelin, the target tissue for
      the autoimmune attack in MS. Although such research has yielded important data,
      furthering our understanding of the disease and opening avenues for possible
      immune-specific therapeutic approaches, attempts to unequivocally associate MS
      with MBP or PLP as primary target antigens in the disease have not been
      successful. This has led in recent years to a new perspective in MS research,
      whereby different CNS antigens are being investigated for their possible role in
      the initiation or progression of MS. Interesting studies in laboratory animals
      show that T-cells directed against certain non-myelin-specific CNS antigens are
      able to cause inflammation of the CNS, albeit without expression of clinical
      disease. However, reactivity to these antigens by MS T-cells has not been
      demonstrated. Conversely, reactivity by MS T-cells to non-myelin-specific
      antigens such as heat shock proteins, could be observed, but the pathogenic
      potential of such reactivity has not been corroborated with the
      encephalitogenicity of the antigen. More relevant to MS pathogenesis may be, as
      we outlined in this review, the autoimmune reactivity directed against minor
      myelin proteins, in particular the CNS-specific myelin oligodendrocyte
      glycoprotein (MOG). Here, we review the current knowledge gathered on T-cell
      reactivity to possible target antigens in MS in the context of their
      encephalitogenic potential, and underline the facets which make MOG a highly
      relevant contender as primary target antigen in MS, albeit not necessarily the
      only one.

PMID- 9776707
TI  - Amelioration of lymphoid hyperplasia and hypergammaglobulinemia in lupus-prone
      mice (gld) by Fas-ligand gene transfer.
AB  - We recently demonstrated that the transplantation of wild-type bone marrow cells
      into lupus-prone mice (gld), resulted in the normalization of autoimmune
      syndromes due to induction of direct elimination of pathogenic cells by apoptosis
      via Fas/Fas ligand (L) interactions. This finding supports the beneficial
      therapeutic effect of Fas-mediated apoptosis on autoimmunity in gld mice. To
      further establish the therapeutic effect of Fas-mediated apoptosis on
      autoimmunity, we investigated the effect of cells transfected with the FasL gene
      on autoimmune symptoms in gld mice. The FasL transfectants exhibited cytotoxic
      activity against gld splenocytes via the Fas/FasL system in vitro. In vivo
      administration of irradiated-FasL transfectants induced a reduction in
      hypergammaglobulinemia, the disappearance of lymphoid hyperplasia and of the
      accumulation of gld cells (B220+ T-cells). Furthermore, in situ nick end
      labelling analysis revealed that cells in the spleen and lymph nodes frequently
      underwent apoptosis. These results clearly indicate that FasL transfectants
      induce the apoptosis of the pathogenic cells responsible for
      hypergammaglobulinemia and lymphoid hyperplasia in gld mice by cell/cell
      interaction via the Fas/FasL system. Thus, ex vivo gene transfer of FasL may
      represent a new therapeutic strategy for autoimmunity caused by the FasL
      dysfunction.

PMID- 9776708
TI  - Intrathymic expression of genes involved in organ specific autoimmune disease.
AB  - Insulin, thyroglobulin and myelin basic protein (MBP) are implicated as
      autoantigens in the autoimmune diseases, insulin-dependent diabetes mellitus
      (IDDM), autoimmune thyroid-disease and multiple sclerosis. Self tolerance to
      these antigens, until recently only thought to be present extrathymically, is
      generally considered to be maintained by 'peripheral' mechanisms, such as clonal
      anergy or clonal ignorance. The techniques of reverse transcription and
      polymerase chain reaction (RT-PCR) were used to investigate the intrathymic
      expression of these genes. Expression was examined in mRNA isolated from complete
      adult rat thymus, various mouse thymic cell-types isolated from fetal thymic
      organ cultures and from neonatal-mouse thymocyte subsets. mRNA for insulin,
      thyroglobulin and MBP were detected in unfractionated adult rat and embryonic
      mouse thymus. Rat thymus expressed both insulin I and II, while mouse thymus only
      expressed insulin II. Thyroglobulin and MBP, but not insulin mRNA were detected
      in mouse MHC class II+ thymic epthelial cells and class II+ dendritic cells and
      in certain thymocyte subsets. The presence of insulin, thyroglobubin and MBP mRNA
      in the thymus has important implications for the development of the T-cell
      repertoire, particularly for the mechanisms of tolerance that prevent
      autoreactivity to these antigens in healthy individuals.

PMID- 9776709
TI  - Clomipramine and imipramine suppress clinical signs and T and B cell response to
      myelin proteins in experimental autoimmune neuritis in Lewis rats.
AB  - 5-Hydroxytryptamine (5-HT) reuptake inhibitors of the zimeldine-type have induced
      polyneuropathies similar to Guillain-Barre syndrome (GBS) in patients with
      endogenous depression. Some monoamine neurotransmitters have been shown to affect
      immune reactions in vivo and in vitro in a concentration-dependent manner. We
      therefore studied the effect of the monoamine reuptake inhibitory anti
      depressants, clomipramine and imipramine on specific immune response and the
      clinical course of experimental autoimmune neuritis (EAN), the animal model of
      GBS in humans. Clomipramine and imipramine both suppressed clinical signs of EAN
      induced by immunization with bovine peripheral nerve myelin (BPM), when given at
      a dose of 20 mg/kg/day intraperitoneally, via osmotic pumps. Clomipramine and
      imipramine reduced the numbers of Th1 cells secreting IFN-gamma in response to
      the neuritogenic myelin proteins BPM, P0 and P2 among lymph node mononuclear
      cells (MNC) from rats with EAN. The levels of cells secreting IgG antibodies to
      BPM, P2 and GM1 in lymph nodes were reduced at the height of EAN in clomipramine
      and imipramine treated animals. The action of clomipramine and imipramine on
      induced IFN-gamma and anti-myelin antibodies suggests that the mechanism for the
      suppressive effect of those substances on EAN symptoms may be due to an action on
      myelin T and B cell autoreactivity. Considering that the main common
      pharmacological principle of clomipramine and imipramine is to increase the
      functional activity of the nor-adrenaline (NA) and serotonin (5-HT) of the
      monoamines, it seems justified to postulate that the actions of clomipramine and
      imipramine demonstrated in this study to some extent involve NA and/or 5-HT. The
      immunomodulatory effects of clomipramine and imipramine call for further research
      on the potential role of drugs acting on the monoamine system in the treatment of
      autoimmune diseases, and for further studies of immunological mechanisms in the
      pathogenesis of depressive disorders.

PMID- 9776710
TI  - Immunoaugmenting effect of FK 506 on experimental allergic encephalomyelitis in
      Lewis rats.
AB  - The effect of the immunosuppressive drug FK 506 on encephalomyelitis (EAE) in
      Lewis rats was studied. Treatment that began during EAE induction delayed EAE
      onset, but when the disease started it was chronic/progressive and of unusual
      severity and duration, leading to death in many animals. Treatment started after
      onset of EAE shortened the disease. Forty seven days after immunization,
      extensive demyelination and inflammation were observed in the spinal cords of
      rats treated with FK 506 from the day of EAE induction. Rats treated after EAE
      onset had only minimal pathological abnormalities.

PMID- 9776711
TI  - Immunization of diabetes-prone or non-diabetes-prone mice with GAD65 does not
      induce diabetes or islet cell pathology.
AB  - Glutamic acid decarboxylase autoimmunity was investigated by immunizing female
      BALB/c, C57B1/6, National Marine Research Institute (NMRI) and non-obese diabetic
      (NOD) mice once or twice with glumatic acid decarboxylase, GAD65, bovine serum
      albumin, or phosphate-buffered saline in incomplete Freunds adjuvant, or not
      treating. Mice immunized with GAD65, showed splinic T-cell reactivity to GAD 65
      in vitro assessed by cytokine secretion. However untreated NOD mice did not. NOD
      mice showed a vigorous IFN-gamma response after one immunization, whereas NMRI
      mice showed a lower response. IL-4 and IL-10 were only detected after two
      immunizations with higher levels in BALB/c, NMRI and NOD mice, compared to
      C57B1/6 mice. High levels of GAD65 antibodies were detected in all mice immunized
      with GAD65, though lower levels were found in C57B1/6 mice. Histological analysis
      of pancreata revealed that no control mice, regardless of treatment, had
      mononuclear cell infiltration in the islets. In NOD mice, peri-insulitis was
      detected in all groups, but less so in GAD65 and bovine serum albumin (BSA)
      immunized animals. These data demonstrate that NOD mice respond more vigorously
      to immunization with GAD65 than non-diabetic mice strains. Furthermore,
      immunization with GAD65 is not sufficient to provoke onset of diabetes in NOD
      mice or induce islet cell pathology in non-diabetes prone mice.

PMID- 9776712
TI  - Low dose poly I:C prevents diabetes in the diabetes prone BB rat.
AB  - Poly I:C, an inducer of IFN-alpha and other cytokines, has been used to study the
      development of diabetes in both the BioBreeding (BB) diabetes prone rat and non
      obese diabetic (NOD) mouse animal models of insulin-dependent diabetes mellitus
      (IDDM). Surprisingly, poly I:C accelerates the disease in the BB rat while
      inhibiting it in the NOD mouse. Since cytokines can have dose related opposing
      effects on immune responses, we hypothesized that the paradoxical effect of
      polyinosinic polycytidylic acid (poly I:C) on diabetes in the two animal models
      is dose related. Accordingly, we compared the incidence of diabetes and degree of
      insulitis in diabetes prone BB rats administered saline and poly I:C at doses
      (0.05 microg/g body weight and 0.1 microg/g body weight) up to 100-fold lower
      than doses (poly-5 microg/g) previously found to accelerate diabetes. In
      addition, the non-specific suppressor activity of mononuclear splenocytes from BB
      rats administered low dose (poly-0.05 microg/g body weight), high dose (poly-5
      microg/g body weight), and saline were compared. The development of diabetes was
      inhibited in rats treated with each dose of poly I:C. The degree of insulitis in
      poly-I:C treated animals was also less severe. The total white blood cell count
      and proportion of RT6+ T-cells and each T-cell subset were unaltered by poly I:C.
      When compared to splenocytes of control animals, splenocytes from poly I:C (0.05
      microg/g body weight) treated rats suppressed responder cell proliferation to
      concanavalin A and alloantigen. However, spleen cells from high dose poly-I:C did
      not suppress responder cell proliferation to alloantigen. In adoptive transfer
      studies, the administration of spleen cells from poly-0.05 treated rats decreased
      the development of diabetes in recipient BB rats. In vitro studies also
      demonstrated that poly-I:C inhibits the proliferative response of BB rat spleen
      cells to concanavalin A. The administration of poly-0.05, but not poly-5.0,
      decreased TNF-alpha mRNA and IL-10 mRNA content in spleen cells. We conclude that
      poly I:C, at a dose 100 times lower than that required to accelerate diabetes
      prevents the development of diabetes in BB rates by interfering with the
      development of insulitis. The induction of suppressor cell activity induced by
      low dose poly-I:C in vivo and the inhibition of T-cell responses by poly-I:C in
      vitro suggests that the diabetes sparing activity of poly I:C is mediated by
      augmented immunoregulatory cell activity. Further studies with poly I:C may be
      important in increasing our understanding of the pathogenesis of IDDM and provide
      a means to prevent it.

PMID- 9776713
TI  - Altered peptide ligands of islet autoantigen Imogen 38 inhibit antigen specific T
      cell reactivity in human type-1 diabetes.
AB  - Type 1 diabetes, insulin-dependent diabetes mellitus (IDDM) results from
      autoimmune T cell-dependent destruction of insulin producing beta-cells in the
      pancreatic islets of Langerhans. T cells from recent-onset IDDM patients
      specifically proliferate to beta cell membrane Ag enriched fractions, containing
      the mitochondrial 38 kD islet antigen (Imogen). Recently, we identified a peptide
      epitope (Imogen p55-70) that is recognized by a 38 kD-specific, Th1 clone from an
      IDDM patient. In animal models of autoimmune diseases, altered self peptide
      ligands (APL) have been used effectively in peptide-based immune prevention or
      therapy. No such APL, however, have been reported so far that can modulate
      autoreactive T-cell responses in IDDM. Here, we have designed APL of p55-70.
      These APL efficiently downregulate in vitro activation of the 38 kD-specific Th1
      clone induced by either p55-70 or by native beta cell autoantigens. Self peptide
      reactive T-cell proliferation could be inhibited only when APL and the self
      peptide were present on the same APC. Unrelated peptides with equal HLA-DR
      binding affinity were not effective, excluding simple MHC competition as the
      mechanism for T-cell modulation. APL triggered upregulation of CD69 and CD25
      expression, but not T-cell proliferation, TCR down-modulation or T-cell anergy.
      Thus, the p55-70 APL inhibit beta cell autoantigen-induced activation of an
      Imogen-reactive T-cell clone derived from an IDDM patient, by acting as partial
      TCR agonists that inhibit TCR down-modulation.

PMID- 9776721
TI  - Model organisms.

PMID- 9776714
TI  - Abnormal DNA damage-inducible protein in cells from Sjogren's syndrome patients.
AB  - Antinuclear antibodies are commonly found in patients with Sjogren's syndrome. It
      has been suggested that the development of antinuclear antibodies depends on the
      activation of the spliceosome and other transcription-related subcellular
      particles, some of which have recently been shown also to function in DNA
      modifying processes, such as DNA repair and V(D)J recombination. These
      observations add weight to a previously proposed model for the aetiology of
      Sjogren's syndrome. This includes the abnormal processing of the T-cell receptor
      and immunoglobulin genes. To test this hypothesis further, the present study on
      DNA-modifying proteins in Sjogren's syndrome was initiated. Gel-shift experiments
      using protein extracted from UV-treated Sjogren cells provided evidence of high
      molecular weight DNA-binding protein in six out of 12 Sjogren patients studied
      (but not among seven healthy controls). Some Sjogren sera displayed antibodies to
      protein extracts from cells treated with psoralen plus UVA radiation. These
      results indicate an abnormal DNA damage-inducible response in Sjogren's syndrome.
      It may therefore be concluded that alterations in nuclear protein may play a role
      in the aetiology of Sjogren's syndrome.

PMID- 9776715
TI  - Reactive oxygen species modified polyguanylic acid: immunogenicity and
      implications for systemic autoimmunity.
AB  - The effect of the hydroxyl radical on polyguanylic acid [poly(G)] was
      investigated with regard to progressive increase of autoantibodies against it in
      systemic lupus erythematosus (SLE) and progressive systemic sclerosis (PSS).
      Rabbits immunized with both native and ROS-poly(G) induced high titre antibodies.
      Immune IgG exhibited a high degree of specificity towards the immunogen,
      reiterated visually by a gel retardation assay. The induced antibodies showed a
      wide range of cross-reactivity with various synthetic polynucleotides exhibiting
      B-, A-, and allied conformations. The specificity of induced antibodies resembled
      the diverse binding characteristics of lupus anti-DNA autoantibodies. Moreover,
      sera from scleroderma patients showed binding to native and ROS-poly(G). SLE and
      PSS autoantibodies showed preferential recognition of ROS-poly(G) over native
      poly(G). These results demonstrate that the hydroxyl modified guanine residues in
      DNA and RNA can induce circulating SLE and PSS autoantibodies.

PMID- 9776720
TI  - Illusions as neuro-signs.

PMID- 9776722
TI  - Huntington's disease.

PMID- 9776723
TI  - Refuge of spandrels.

PMID- 9776724
TI  - Stretch-induced alkalinization of feline papillary muscle: an autocrine-paracrine
      system.
AB  - Myocardial stretch is a well-known stimulus that leads to hypertrophy. Little is
      known, however, about the intracellular pathways involved in the transmission of
      myocardial stretch to the cytoplasm and nucleus. Studies in neonatal
      cardiomyocytes demonstrated stretch-induced release of angiotensin II (Ang II).
      Because intracellular alkalinization is a signal to cell growth and Ang II
      stimulates the Na+/H+ exchanger (NHE), we studied the relationship between
      myocardial stretch and intracellular pH (pHi). Experiments were performed in cat
      papillary muscles fixed by the ventricular end to a force transducer. Muscles
      were paced at 0.2 Hz and superfused with HEPES-buffered solution. pHi was
      measured by epifluorescence with the acetoxymethyl ester form of the pH-sensitive
      dye 2',7'-bis(2-carboxyethyl)-5,6-carboxyfluorescein (BCECF-AM). Each muscle was
      progressively stretched to reach maximal developed force (Lmax) and maintained in
      a length that was approximately 92% Lmax (Li). During the "stretch protocol,"
      muscles were quickly stretched to Lmax for 10 minutes and then released to Li;
      pHi significantly increased during stretch and came back to the previous value
      when the muscle was released to Li. The increase in pHi was eliminated by (1)
      specific inhibition of the NHE (EIPA, 5 micromol/L), (2) AT1-receptor blockade
      (losartan, 10 micromol/L), (3) inhibition of protein kinase C (PKC)
      (chelerythrine, 5 micromol/L), (4) blockade of endothelin (ET) receptors with a
      nonselective (PD 142,893, 50 nmol/L) or a selective ETA antagonist (BQ-123, 300
      nmol/L). The increase in pHi by exogenous Ang II (500 nmol/L) was also reduced by
      both ET-receptor antagonists. Our results indicate that after myocardial stretch,
      pHi increases because of stimulation of NHE activity. This involves an autocrine
      paracrine mechanism in which protein kinase C, Ang II, and ET play crucial roles.

PMID- 9776726
TI  - Slow conduction in cardiac tissue, II: effects of branching tissue geometry.
AB  - In cardiac tissue, functional or structural current-to-load mismatches can induce
      local slow conduction or conduction block, which are important determinants of
      reentrant arrhythmias. This study tested whether spatially repetitive mismatches
      result in a steady-state slowing of conduction. Patterned growth of neonatal rat
      heart cells in culture was used to design unbranched cell strands or strands
      releasing branches from either a single point or multiple points at periodic
      intervals. Electrical activation was followed optically using voltage-sensitive
      dyes under control conditions and in elevated [K+]o (5.8 and 14.8 mmol/L,
      respectively; in the latter case, propagation was carried by the L-type Ca2+
      current). Preparations with multiple branch points exhibited discontinuous and
      slow conduction that became slower with increasing branch length and/or
      decreasing inter-branch distance. Compared with unbranched strands, conduction
      was maximally slowed by 63% under control conditions (from 44.9+/-3.4 to 16.7+/
      1.0 cm/s) and by 93% in elevated [K+]o (from 15.7+/-2.3 to 1.1+/-0.2 cm/s). Local
      activation delays induced at a single branch point were significantly larger than
      the delays per branch point in multiple branching structures. Also, selective
      inactivation of inward currents in the branches induced conduction blocks. These
      2 observations pointed to a dual role of the branches in propagation: whereas
      they acted as current sinks for the approaching activation thus slowing
      conduction ("pull" effect), they supplied, once excited, depolarizing current
      supporting downstream activation ("push" effect). This "pull and push" action
      resulted in a slowing of conduction in which the safety was largely preserved by
      the "push" effect. Thus, branching microarchitectures might contribute to slow
      conduction in tissue with discontinuous geometry, such as infarct scars and the
      atrioventricular node.

PMID- 9776727
TI  - Characterization of a slowly inactivating outward current in adult mouse
      ventricular myocytes.
AB  - We recently have reported that suppression of the slowly inactivating component
      of the outward current, Islow, in ventricular myocytes of transgenic mice (long
      QT mice) overexpressing the N-terminal fragment and S1 segment of Kv1.1 resulted
      in a significant prolongation of action potential duration and the QT interval.
      Here we describe the detailed biophysical properties and physiological role of
      Islow by applying the whole-cell patch-clamp technique at both room temperature
      and 37 degreesC. This current activates rapidly with time constants ranging from
      3.8+/-0.8 ms at -20 mV to 2.1+/-0.5 ms at 50 mV at room temperature. The half
      activation voltage and slope factor are -12.5+/-2.6 mV and 7. 7+/-1.0 mV,
      respectively. The inactivation of this current is slow compared with the fast
      inactivating component Ito, with time constants of approximately 100 ms at 37
      degreesC. The steady-state inactivation of Islow is not temperature-dependent,
      with half-inactivation voltages and slope factors of -35.1+/-1.3 and -5. 4+/-0.4
      mV at 37 degreesC, and -37.6+/-1.8 and -5.8+/-0.6 mV at room temperature. Double
      exponentials were required to describe the time-dependent recovery of Islow from
      steady-state inactivation, with time constants of 233+/-34 and 3730+/-702 ms at
      37 degreesC, and 830+/-240 and 8680+/-2410 ms at room temperature. Islow is
      highly sensitive to 4-aminopyridine but is insensitive to tetraethylammonium,
      alpha-dendrotoxin, and E-4031. Stimulation with action-potential waveforms under
      voltage-clamp mode revealed that this current plays an important role in the
      early and middle phases of repolarization of the cardiac action potential. We
      conclude that the biophysical properties and pharmacological profiles of Islow
      are similar to those of Kv1.5-encoded currents.

PMID- 9776725
TI  - Slow conduction in cardiac tissue, I: effects of a reduction of excitability
      versus a reduction of electrical coupling on microconduction.
AB  - It was the aim of this study to characterize the spread of activation at the
      cellular level in cardiac tissue during conduction slowing, a key element of
      reentrant arrhythmias; therefore, activation patterns were assessed at high
      spatiotemporal resolution in narrow (70 to 80 microm) and wide (230 to 270
      microm) linear strands of cultured neonatal rat ventricular myocytes, using
      multiple site optical recording of transmembrane voltage. Slow conduction was
      induced by graded elevation of [K+]o, by applying tetrodotoxin, or by exposing
      the preparations to the gap junctional uncouplers palmitoleic acid or 1-octanol.
      The main findings of the study are 4-fold: (1) gap junctional uncoupling reduced
      conduction velocity (range, 37 to 47 cm/s under control conditions) to a
      substantially larger extent before block (</=1 cm/s; ultra-slow conduction) than
      did a reduction of excitability (range, approximately 10 to 15 cm/s); (2)
      activation wavefronts during uncoupling meandered within the boundaries of the
      preparations, resulting in a pronounced additional slowing of conduction in wide
      cell strands; (3) at the cellular level, propagation during uncoupling-induced
      ultra-slow conduction was sustained by sequentially activated tissue patches,
      each of which consisted of a few cells being activated simultaneously; and (4)
      depending on the uncoupler used, maximal action potential upstroke velocities
      during ultra-slow conduction were either slightly (palmitoleic acid) or highly (1
      octanol) depressed. Thus, depolarizing inward currents, the spatial pattern and
      degree of gap junctional coupling, and geometrical factors all contribute in a
      concerted manner to conduction slowing, which, at its extreme (0.25 cm/s measured
      over 1 mm), can reach values low enough to permit, theoretically, reentrant
      excitation to occur in minuscule areas of cardiac tissue (<<1 mm2).

PMID- 9776728
TI  - Interferon induction of TAP1: the phosphatase SHP-1 regulates crossover between
      the IFN-alpha/beta and the IFN-gamma signal-transduction pathways.
AB  - Interferon (IFN)-gamma and IFN-alpha/beta induction of the transporter associated
      with antigen processing-1 (TAP1) promoter was compared in HeLa cells and
      endothelial cells (ECs). In HeLa cells, IFN-gamma acts through
      Stat1alpha/Stat1alpha homodimers binding to the gamma activating sequence (GAS)
      and IFN-alpha/beta acts through Stat1/Stat2/p48 binding to the IFN-stimulated
      response element (ISRE). In ECs, however, IFN-gamma and IFN-alpha/beta act
      through both the GAS and ISRE. The basis of the IFN signaling crossover in ECs
      was investigated. HeLa and ECs contain similar ratios of Stat1alpha to Stat2
      proteins, and IFN-alpha/beta also activates the same Janus kinases (JAKs) (Jak1
      and tyrosine kinase (Tyk) 2 but not Jak2). However, IFN-alpha/beta activates more
      Stat1alpha than does IFN-gamma in ECs, whereas the reverse occurs in HeLa, and
      expression of the IFN-alpha/beta receptor-associated phosphatase SHP-1 is much
      lower in ECs than HeLa cells. Overexpression of SHP-1 in ECs blocks IFN
      alpha/beta signaling through GAS, and expression of a dominan negative SHP-1 in
      HeLa cells permits IFN-alpha/ss signaling through GAS, demonstrating a role for
      SHP-1 in regulating crossovers between the IFN-alpha/beta and IFN-gamma signaling
      pathways.

PMID- 9776729
TI  - p38 Kinase is a negative regulator of angiotensin II signal transduction in
      vascular smooth muscle cells: effects on Na+/H+ exchange and ERK1/2.
AB  - Activation of the Na+/H+ exchanger isoform-1 (NHE-1) by angiotensin II is an
      early signal transduction event that may regulate vascular smooth muscle cell
      (VSMC) growth and migration. Many signal transduction events stimulated by
      angiotensin II are mediated by the mitogen-activated protein (MAP) kinases. To
      define their roles in angiotensin II-mediated NHE-1 activity, VSMCs were treated
      with angiotensin II and the activities of p38, c-Jun N-terminal kinase (JNK), and
      extracellular signal-regulated kinases 1 and 2 (ERK1/2) were measured.
      Angiotensin II rapidly (peak, 5 minutes) activated p38 and ERK1/2, whereas JNK
      was activated more slowly (peak, 30 minutes). Because angiotensin II stimulated
      Na+/H+ exchange within 5 minutes, the effects of p38 and ERK1/2 antagonists on
      Na+/H+ exchange were studied. The MEK-1 inhibitor PD98059 decreased ERK1/2
      activity and Na+/H+ exchange stimulated by angiotensin II. In contrast, the
      specific p38 antagonist SKF-86002 increased Na+/H+ exchange. Two mechanisms were
      identified that may mediate the effects of p38 and SKF-86002 on angiotensin II
      stimulated Na+/H+ exchange. First, angiotensin II activation of ERK1/2 was
      increased 1. 5- to 2.5-fold (depending on assay technique) in the presence of SKF
      86002, demonstrating that p38 negatively regulates ERK1/2. Second, the ability of
      angiotensin II-stimulated MAP kinases to phosphorylate a glutathione S
      transferase fusion protein containing amino acids 625 to 747 of NHE-1 in vitro
      was analyzed. The relative activities of endogenous immunoprecipitated p38,
      ERK1/2, and JNK were 1.0, 2.0, and 0.05 versus control, respectively suggesting
      that p38 and ERK1/2, but not JNK, may phosphorylate NHE-1 in VSMC. These data
      indicate important roles for p38 and ERK1/2 in angiotensin II-mediated regulation
      of the Na+/H+ exchanger in VSMC.

PMID- 9776730
TI  - Vascular endothelial growth factor upregulates the expression of matrix
      metalloproteinases in vascular smooth muscle cells: role of flt-1.
AB  - Vascular endothelial growth factor (VEGF) is a critical regulator of angiogenesis
      that stimulates proliferation, migration, and proteolytic activity of endothelial
      cells. Although the mitogenic activity of VEGF is endothelial cell specific,
      recent reports indicate VEGF is able to stimulate chemotaxis and tissue factor
      production in monocytes. VEGF-stimulated activity in monocytes is mediated by the
      VEGF receptor flt-1. The purpose of the present study was to investigate the
      effects of VEGF on another major cell type in the vascular wall, namely, the
      vascular smooth muscle cell (SMC). Using cultured cells, we showed that VEGF has
      a minimal mitogenic effect on SMCs, which is in accordance with published data.
      However, VEGF treatment significantly enhanced production of matrix
      metalloproteinase (MMP)-1, -3, and -9 by human SMCs. The upregulation of MMP-1
      and MMP-9 was pronounced, and the stimulation for MMP-3 was less prominent.
      Stimulation could be demonstrated at both protein and mRNA levels, as reflected
      by ELISA, zymography, and Northern blot analysis. To explore the signal
      transduction pathway for the effect of VEGF on SMCs, we studied the expression of
      2 high-affinity VEGF receptors, the kinase insert domain-containing receptor
      (KDR) and flt-1, in human SMCs. Both reverse transcriptase-polymerase chain
      reaction and immunoblotting revealed the expression of flt-1. Immunoprecipitation
      followed by immunoblotting illustrated phosphorylation of the flt-1 receptor
      after VEGF treatment. Similar methodology failed to detect expression of KDR in
      human SMCs. These data suggest the role of flt-1 in mediating VEGF-stimulated MMP
      expression of SMCs. The physiological relevance of MMP upregulation was studied
      by examining VEGF-stimulated SMC migration through 2 synthetic extracellular
      matrix barriers, Matrigel and Vitrogen. Our results indicate that VEGF treatment
      accelerated SMC migration through both barriers, and that this response was
      blocked by MMP inhibition in Matrigel, which supports a permissive role of MMP in
      SMC migration. These data are the first to show a direct effect of VEGF on SMCs.
      SMC-derived MMPs may be an additional source of proteases to digest vascular
      basement membrane, which is a crucial step in the initial stage of angiogenesis.
      The MMPs may also contribute to SMC migration in angiogenesis and atherogenesis.

PMID- 9776731
TI  - Calcium- and protein kinase C-dependent activation of the tyrosine kinase PYK2 by
      angiotensin II in vascular smooth muscle.
AB  - Angiotensin II (Ang II) induces vascular smooth muscle cell (VSMC) growth by
      activating Gq-protein-coupled AT1 receptors, which leads to elevation of
      cytosolic Ca2+ ([Ca2+]i) and activation of protein kinase C (PKC) and mitogen
      activated protein kinases. To assess the link between these Ang II-induced
      signaling events, we examined the effect of Ang II on the proline-rich tyrosine
      kinase (PYK2), previously found to be activated by a variety of stimuli that
      increase [Ca2+]i or activate PKC. PYK2 distribution was demonstrated in rat
      aortic tissue and in cultured VSMC by immunohistochemistry, revealing a cytosolic
      distribution distinct from smooth muscle alpha-actin, focal adhesion kinase, or
      paxillin. The involvement of PYK2 in Ang II signaling was measured by
      immunoprecipitation and immune complex kinase assays. Treatment of quiescent VSMC
      with Ang II resulted in a concentration- and time-dependent increase in PYK2
      tyrosine phosphorylation and kinase activity in PYK2 immunoprecipitates. PYK2
      phosphorylation was inhibited by AT1 receptor blockade and was attenuated by
      downregulation of PKC or the chelation of [Ca2+]i. Treatment with either phorbol
      ester or Ca2+ ionophore also increased PYK2 phosphorylation, suggesting that PKC
      activation and/or increased [Ca2+]i are both necessary and sufficient to activate
      PYK2. Activation of PYK2 by Ang II was also associated with increased PYK2-src
      complex formation, suggesting that PYK2 activation represents a potential link
      between Ang II-stimulated [Ca2+]i and PKC activation with downstream signaling
      events such as mitogen-activated protein kinase activation involved in the
      regulation of VSMC growth.

PMID- 9776732
TI  - Regulation of angiopoietin-2 mRNA levels in bovine microvascular endothelial
      cells by cytokines and hypoxia.
AB  - Angiopoietin-2 (Ang2) is a ligand for the endothelial cell tyrosine kinase
      receptor Tie2 and counteracts blood vessel maturation/stability mediated by
      angiopoietin-1 (Ang1), the other known ligand of Tie2. Using degenerate
      oligonucleotides and reverse transcriptase-polymerase chain reaction, we have
      screened bovine microvascular endothelial (BME), aortic, lymphatic, pulmonary
      artery, and transformed fetal aortic endothelial cells, as well as rat smooth
      muscle cells for Ang1 and Ang2 expression. Except for high Ang2 mRNA levels found
      in BME cells, none of the endothelial cell types studied expressed appreciable
      levels of Ang1 or Ang2 mRNAs, whereas smooth muscle cells expressed both Ang1 and
      Ang2. BME cell Ang2 mRNA levels were increased by vascular endothelial growth
      factor (1.9- to 2.9-fold), basic fibroblast growth factor (1.6- to 2-fold), both
      cytokines in combination (2.9- to 4-fold), and hypoxia (3.1- to 5.6-fold) and
      were decreased by Ang1 (31% to 70%) or transforming growth factor-ss1 (64% to
      81%). Ang2 also decreased (60% to 82%) BME cell Ang2 mRNA. mRNA levels for the
      Tie1 or Tie2 receptors were only slightly modulated under the conditions
      described above. These findings suggest that the angiogenic effect of a number of
      regulators may be achieved in part through the regulation of an autocrine loop of
      Ang2 activity in microvascular endothelial cells.

PMID- 9776735
TI  - AHA journals at the forefront of cardiology : A report on excellence 

PMID- 9776733
TI  - Human heart generates complement proteins that are upregulated and activated
      after myocardial infarction.
AB  - In human heart, we detected mRNAs and proteins for C1q, C1r, C1s, C2, C3, C4, C5,
      C6, C7, C8, and C9 with the use of reverse transcriptase-polymerase chain
      reaction, Western blotting, and immunohistochemical techniques. We found an
      upregulation of both mRNAs and proteins in areas of recent and old myocardial
      infarctions. In both situations, the classical complement pathway was activated,
      with C4d, C3d, and the membrane attack complex (C5b-9) being deposited on damaged
      cardiac myocytes. These activated complement components were also identified on
      Western blots of infarcted tissue. Complement mRNAs in infarcted heart tissue
      were higher than those in liver, and liver complement mRNAs were not upregulated
      in cases with infarcted hearts. Our results establish that (1) complement
      proteins are endogenously produced by human heart; (2) the classical complement
      pathway is fully activated after myocardial infarction; (3) complement activation
      is directly involved in myocardial damage after ischemic insults; and (4) damage
      from complement activation may be chronically sustained. These data suggest that
      inhibition of the complement system should be effective in treating myocardial
      infarction.

PMID- 9776734
TI  - Angiotensin and endothelin: messengers that couple ventricular stretch to the
      Na+/H+ exchanger and cardiac hypertrophy.

PMID- 9776736
TI  - Natural covalent complexes of nucleic acids and proteins: some comments on
      practice and theoryon the path from well-known complexes to new ones.

PMID- 9776737
TI  - Kinetics and thermodynamics of i-DNA formation: phosphodiester versus modified
      oligodeoxynucleotides.
AB  - At slightly acidic or even neutral pH, oligodeoxynucleotides that include a
      stretch of cytidines have been shown to form a tetrameric structure in which two
      parallel-stranded duplexes have their hemiprotonated C.C+base pairs face to face
      and fully intercalated, in a so-called i-motif. Cytosine-rich pyrimidine
      oligodeoxynucleotides can form an intramolecular i-motif. We have studied the
      ability of several DNA analogs to fold into this structure. Evidence for folding
      was provided by thermal denaturation. We have shown that phosphorothioate and
      phosphodiester oligodeoxynucleotides, but not methylphosphonate or PNA oligomers,
      may form the i-motif. Four different PS oligodeoxynucleotides were compared with
      their PO counterparts. In all cases, the melting temperature (Tm) of the
      phosphorothioate oligomer was equal or slightly inferior (by 2-3 degreesC) to the
      Tmof the natural oligodeoxynucleotide. For long oligodeoxynucleotides, a small
      change of pH leads to a completely different melting profile: the curves are
      reversible at pH 6.4 or lower, and a hysteresis is obtained at pH 6.8 or higher;
      cooling and heating curves were not superimposed, allowing us to determine the
      rate constants of association (kon) and dissociation (koff) as a function of the
      temperature: these rate constants give linear Arrhenius plots, in agreement with
      the prediction of the two-state model of association-dissociation. The activation
      energy Eonis strongly negative and, at neutral pH, the phosphorothioate
      associates and dissociates nine times faster than the phosphodiester
      oligodeoxynucleotide of identical sequence.

PMID- 9776738
TI  - Role of the DNA ligase III zinc finger in polynucleotide binding and ligation.
AB  - Mammalian DNA ligase III exists as two distinct isoforms denoted alpha and beta.
      Both forms possess a motif that is homologous to the putative zinc finger present
      in poly(ADP-ribose) polymerase. Here, the role of this motif in the binding and
      ligation of nicked DNA and RNA substrates in vitro has been examined in both
      isoforms. Disruption of the putative zinc finger did not affect DNA ligase III
      activity on nicked DNA duplex, nor did it abolish DNA ligase III-alpha activity
      during DNA base excision repair in a cell-free assay. In contrast, disruption of
      this motif reduced 3-fold the activity of both DNA ligase III isoforms on nicked
      RNA present in RNA/DNA homopolymers. Furthermore, whereas disruption of the motif
      did not prevent binding of DNA ligase III to nicked DNA duplex, binding to nicked
      RNA homopolymers was reduced approximately 10-fold. These results suggest that
      the putative zinc finger does not stimulate DNA ligase III activity on simple
      nicked DNA substrates, but indicate that this motif can target the binding and
      activity of DNA ligase III to nicked RNA homopolymer. The implications of these
      results to the cellular role of the putative zinc finger are discussed.

PMID- 9776739
TI  - Suppression of electrophoretic anomaly of bent DNA segments by the structural
      property that causes rapid migration.
AB  - Intrinsic DNA curvature is speculated to be a common feature of all satellite DNA
      sequences and may aid in the tight winding of DNA in constitutive
      heterochromatin. Several satellite DNAs, however, show unusually rapid migration
      in non-denaturing polyacrylamide gels, which is just the opposite behavior of
      that shown by curved DNA structures. Employing bovine satellite I DNA monomer, we
      attempted to understand the molecular mechanism of 'rapid migration'. The
      phenomenon of rapid migration was temperature-dependent and to a small extent
      polyacrylamide-concentration-dependent. Physiological or near-physiological
      concentrations of Mg2+and Ca2+ions bent the rapid migrating DNA segment.
      Predominance of purine-purine base stacking over purine-pyrimidine in nucleotide
      sequence was strongly indicated to be the cause of the rapid migration.
      Furthermore, they seemed to be implicated in the formation of induced DNA bend.
      We also found that the satellite I monomer contains an intrinsic DNA curvature as
      do many other satellites. Heretofore, the rapid migration property has concealed
      the presence of curvature.

PMID- 9776740
TI  - The hepatitis B virus post-transcriptional regulatory element contains two
      conserved RNA stem-loops which are required for function.
AB  - Human Hepatitis B Virus (HBV) RNAs contain a cis -acting sequence, the post
      transcriptional regulatory element (HPRE), which facilitates the cytoplasmic
      localization of intronless transcripts. Our previous studies have shown that the
      HPRE is composed of at least two independent sub-elements, HPREalpha and
      HPREbeta, which co-activate a reporter for RNA export in a greater than additive
      manner. Utilizing deletion, mutation and co-variational analyses, we have
      identified three regions important for full HPRE activity. The three separate
      regions of the HPRE function can function independently in a dose-dependent
      manner when multimerized. Two of these regions contain stem loops, HSLalpha and
      HSLbeta1, which are necessary for full HPRE function. These structures are
      conserved throughout the mammalian Hepadnaviruses. Disruption of either stem-loop
      structure by mutagenesis decreases HPRE function while compensatory mutations
      restore activity. The location of the stem-loops in the genome reveal that they
      are present in all of the HBV transcripts. HSLalpha and HSLbeta1 are likely to
      contain the binding sites for the cellular factor(s) which mediates HPRE
      function.

PMID- 9776741
TI  - EcoKI with an amino acid substitution in any one of seven DEAD-box motifs has
      impaired ATPase and endonuclease activities.
AB  - For type I restriction systems, recently determined nucleotide sequences predict
      conserved amino acids in the subunit that is essential for restriction but not
      modification (HsdR). The conserved sequences emphasize motifs characteristic of
      the DEAD-box family of proteins which comprises putative helicases, and they
      identify a new candidate for motif IV. We provide evidence based on an analysis
      of Eco KI which supports both the relevance of DEAD-box motifs to the mechanism
      of restriction and the new definition of motif IV. Amino acid substitutions
      within the newly identified motif IV and those in six other previously identified
      DEAD-box motifs, but not in the original motif IV, confer restriction-deficient
      phenotypes. We have examined the relevance of the DEAD-box motifs to the
      restriction pathway by determining the steps permitted in vitro by the defective
      enzymes resulting from amino acid substitutions in each of the seven motifs. Eco
      KI purified from the seven restriction-deficient mutants binds to an unmethylated
      target sequence and, in the presence of AdoMet, responds to ATP by undergoing the
      conformational change essential for the pathway of events leading to DNA
      cleavage. The seven enzymes have little or no ATPase activity and no endonuclease
      activity, but they retain the ability to nick unmodified DNA, though at reduced
      rates. Nicking of a DNA strand could therefore be an essential early step in the
      restriction pathway, facilitating the ATP-dependent translocation of DNA,
      particularly if this involves DNA helicase activity.

PMID- 9776742
TI  - Identification of AP-2 as an interactive target of Rb and a regulator of the G1/S
      control element of the hamster histone H3.2 promoter.
AB  - Previous studies have established that a 32 bp cis -regulatory region, referred
      to as the H3core spanning -241 to -210 of the hamster histone H3.2 promoter, is
      critical for its G1/S-phase induction of transcription. Here we report that the
      transcription factor AP-2 is a major component of the protein complex which
      interacts with the H3core from hamster nuclear extracts. In search of the control
      mechanism(s) whereby AP-2 can mediate cell cycle regulation of the histone H3.2
      promoter, we found that AP-2 can physically interact with the retinoblastoma (Rb)
      tumor suppressor protein in vitro , and when over-expressed, can also associate
      with Rb in vivo . Importantly, in contrast to the majority of Rb binding
      proteins, the C-terminal domain of Rb alone is sufficient for its interaction
      with AP-2. Using a reporter gene system linking tandem copies of the H3core to a
      heterologous minimal promoter, we demonstrated that over-expression of AP-2
      proteins results in transactivation of the reporter gene through the H3core in a
      sequence-specific but orientation-independent manner. Additionally, this
      stimulative effect was suppressed by co-expression of Rb. Thus, AP-2, through its
      physical and functional interaction with Rb, may contribute to the cell cycle
      regulation of its target genes.

PMID- 9776743
TI  - Molecular cloning of a cDNA encoding human SPH-binding factor, a conserved
      protein that binds to the enhancer-like region of the U6 small nuclear RNA gene
      promoter.
AB  - Many vertebrate small nuclear RNA gene promoters contain an SPH motif in their
      distal control regions that can confer transcriptional stimulation by RNA
      polymerase II or RNA polymerase III. Using the human U6 gene SPH motif as a
      probe, we isolated a cDNA encoding human SPH-binding factor (hSBF) from a HeLa
      cell expression library. The coding region of hSBF is almost identical to ZNF143,
      a 626 amino acid, seven zinc finger protein of previously unknown function.
      Furthermore, the predicted amino acid sequence of hSBF is highly homologous to
      Xenopus laevis and mouse Staf proteins, that bind to SPH motifs and stimulate
      transcription of selenocysteine tRNA gene promoters. Recombinant hSBF expressed
      in vitro or from Escherichia coli bound specifically to the human U6 gene SPH
      motif as shown by DNase I footprinting and electrophoretic mobility shift assays
      using various mutant SPH sites as competitors. Antibodies prepared against
      recombinant hSBF inhibited assembly of native SBF-DNA complexes. Immunodepleted
      HeLa S100 transcription extract no longer supported elevated levels of
      transcription by RNA polymerase III from a U6 promoter containing an SPH motif,
      whereas addition of recombinant hSBF protein to the immunodepleted extract
      reconstituted stimulated transcription.

PMID- 9776744
TI  - Primer extension analysis of eukaryotic ribosome-mRNA complexes.
AB  - Conditions are described for using a primer extension inhibition (toeprinting)
      assay to study the initiation step of protein synthesis in rabbit reticulocyte
      lysates. These studies revealed that chloramphenicol acetyltransferase mRNA,
      which is widely used as a reporter, forms unusually labile initiation complexes.
      This and other unexpected problems were solved by adjustments in pH and
      temperature during the reverse transcriptase step. Complications that may occur
      during the ribosome binding step were also examined, including the possibility of
      rapid mRNA degradation. The suitability of inhibitors commonly used to block the
      elongation phase of translation was studied. The refined toeprinting assay was
      used to confirm context-dependent selection of the AUG start codon. Absence of
      the m7G cap did not subvert the process wherein initiation is restricted to the
      first AUG codon. The fidelity of initiation was impaired, however, when NaF was
      introduced during the ribosome binding step. In a preliminary assessment of the
      processivity of scanning, no dissociation of 40S ribosomal subunits was detected
      as the distance from the cap to the AUG codon was increased to nearly 300 bases.
      With an mRNA that contains a pseudoknot upstream from the AUG codon, the
      toeprinting assay revealed 40S ribosomal subunits trapped behind the base paired
      structure. Thus the assay is usable for mapping some intermediates as well as for
      detecting conventional 80S initiation complexes.

PMID- 9776745
TI  - Cationic oligonucleotides can mediate specific inhibition of gene expression in
      Xenopus oocytes.
AB  - Base-specific hydrogen bonding between an oligonucleotide and the purines in the
      major groove of a DNA duplex provide an approach to selective inhibition of gene
      expression. Oligonucleotide-mediated triplex formation in vivo may be enhanced by
      a number of different chemical modifications. We have previously described an in
      vitro analysis of triplex formation using oligonucleotides containing
      internucleoside phosphate linkages modified with the cation N , N -diethyl
      ethylenediamine (DEED). When compared with unmodified oligonucleotides of
      identical base composition, DEED-modified oligonucleotides were better able to
      form DNA triplexes under conditions that approximate the pH, magnesium and
      potassium levels found in vivo . Here we report the ability of DEED-modified
      oligonucleotides to inhibit the expression of plasmid DNA injected into Xenopus
      oocytes. Inhibition is specific to plasmids containing a triplex formation target
      and sensitive to sequence alteration in the triplex forming target site.
      Inhibition of gene expression was nearly complete when oligonucleotide and
      plasmid were mixed together prior to injection. Inhibition was partial when
      oligonucleotide was injected first and not evident when plasmid was injected and
      allowed to form chromatin prior to oligonucleotide injection. Thus, access to DNA
      is a determining factor in effective triplex inhibition of gene expression.

PMID- 9776746
TI  - Unstable retrovirus mutants with acquired transforming activity: rapid changes in
      the number of repeats of a specific junD polynucleotide segment.
AB  - We have previously reported that the non-transforming jun D (wild type) gene can
      acquire transforming activity through spontaneous mutations when it is replicated
      through avian replication-competent retrovirus vectors in chicken embryo
      fibroblasts. In two of these spontaneous mutants, T1 and T2, which were isolated
      from proviral DNA in the same transformed cell clone, a specific 48 bp
      polynucleotide segment of the jun D coding sequence was tandemly repeated three
      and five times, respectively. We report here that the number of direct repeats in
      these mutants rapidly changes (mostly decreases) in the context of either RSV
      based replication-competent or MLV-based replication-defective retroviruses, most
      likely during the process of reverse transcription, while these mutations are
      stable in the cellular chromosome. We also show that the growth conditions of the
      infected culture modulate the proportions of polymorphic proviral populations in
      the infected culture. We finally discuss the possible molecular mechanisms that
      generate genetic diversity in these amplification mutants.

PMID- 9776747
TI  - The phage-type PclpP-53 plastid promoter comprises sequences downstream of the
      transcription initiation site.
AB  - The existence of a phage-type plastid transcription machinery (NEP), related to
      the mitochondrial RNA polymerase, has been recognized only recently. Here we
      report the cis sequences required for transcription initiation by the phage-type
      enzyme. The promoter chosen for the study, PclpP-53, is well expressed in tobacco
      leaves, unlike most NEP promoters. Promoter definition was carried out in vivo ,
      in transplastomic tobacco plants expressing a uidA reporter gene from PclpP-53
      promoter derivatives. We report here that sequences from -5 to +25 (relative to
      the transcription initiation site) are sufficient to support specific
      transcription initiation. Requirement of sequences downstream of the
      transcription initiation site contrasts with mitochondrial promoters, which have
      conserved sequences predominantly upstream. The promoter defined here is
      conserved in liverworts and conifers, indicating that the phage-type
      transcription machinery appeared in plastids early on during the evolution of
      land plants. The PclpP-53 promoter sequences are present in rice but do not
      function, suggesting that PclpP-53 recognition specificity is absent in some
      monocots.

PMID- 9776748
TI  - X-ray analysis of a complex of Escherichia coli uracil DNA glycosylase (EcUDG)
      with a proteinaceous inhibitor. The structure elucidation of a prokaryotic UDG.
AB  - Uracil-DNA glycosylase (UDG), a key highly conserved DNA repair enzyme involved
      in uracil excision repair, was discovered in Escherichia coli . The Bacillus
      subtilis bacteriophage, PBS-1 and PBS-2, which contain dUMP residues in their
      DNA, express a UDG inhibitor protein, Ugi which binds to UDG very tightly to form
      a physiologically irreversible complex. The X-ray analysis of the E. coli UDG (
      Ec UDG)-Ugi complex at 3.2 A resolution, leads to the first structure elucidation
      of a bacterial UDG molecule. This structure is similar to the enzymes from human
      and viral sources. A comparison of the available structures involving UDG permits
      the delineation of the constant and the variable regions of the molecule.
      Structural comparison and mutational analysis also indicate that the mode of
      action of the enzyme from these sources are the same. The crystal structure shows
      a remarkable spatial conservation of the active site residues involved in DNA
      binding in spite of significant differences in the structure of the enzyme
      inhibitor complex, in comparison with those from the mammalian and viral sources.
      Ec UDG could serve as a prototype for UDGs from pathogenic prokaryotes, and
      provide a framework for possible drug development against such pathogens with
      emphasis on features of the molecule that differ from those in the human enzyme.

PMID- 9776749
TI  - Determination of spontaneous loss of heterozygosity mutations in Aprt
      heterozygous mice.
AB  - A mouse model was generated to investigate loss of heterozygosity (LOH) events in
      somatic cells. The adenine phosphoribosyltransferase ( Aprt ) gene was disrupted
      in embryonic stem cells using a conventional gene targeting approach and
      subsequently Aprt hetero-zygous and homozygous mice were derived. Aprt homozygous
      deficient animals were viable though the mendelian inheritance pattern was
      skewed. On average these mice died at 6 months of age from severe renal failure.
      In T-lymphocytes of Aprt heterozygous mice the mean spontaneous mutant frequency
      at the Aprt locus was 8.7 x 10(-6) while the frequency was 0.8 x 10(-6) at the
      hypoxanthine phosphoribosyltransferase locus. In order to determine whether LOH
      events contribute to the high spontaneous mutant frequency at the Aprt locus, 140
      Aprt mutant T-lymphocyte clones were expanded and analysed by allele-specific
      PCR. In 97 (69%) of these clones the wild-type allele had been lost. Nine of the
      mutant clones were characterized in more detail using dual-coloured fluorescence
      in situ hybridization analysis. Five out of six of the mutant clones which arose
      from an LOH event, based on the PCR assay, contained a duplication of the
      targeted allele. Therefore, mitotic recombination or chromosome loss followed by
      duplication of the remaining homologue appears to be the predominant mechanism
      for the in vivo generation of Aprt mutant T-lymphocytes.

PMID- 9776750
TI  - A simple polypyrimidine repeat acts as an artificial Rho-dependent terminator in
      vivo and in vitro.
AB  - In this paper, we present evidence that an efficient Rho-dependent terminator can
      be created by introducing a simple (AG/TC) n DNA repeat into a transcription
      unit. The Rho termination activity in vivo and in vitro is dependent on the
      length and the orientation of the insert. The transcription of at least 30 bp of
      the (AG/TC) n repeat in the orientation encoding the (rUrC) n sequence on the
      transcript leads to Rho-dependent termination at a downstream non-terminator
      site. Our results indicate that the high efficiency of this artificial Rho
      dependent terminator is due to optimal interactions between the (rUrC) n RNA
      sequence and Rho protein. Thus, our findings strongly suggest that an adequate
      loading site is the primary determinant for Rho termination activity and provide
      a more defined system for future investigations.

PMID- 9776751
TI  - Cloning and stable maintenance of DNA fragments over 300 kb in Escherichia coli
      with conventional plasmid-based vectors.
AB  - Bacterial artificial chromosome (BAC) and P1-derived artificial chromosome (PAC)
      systems were previously developed for cloning of very large eukaryotic DNA
      fragments in bacteria. We report the feasibility of cloning very large fragments
      of eukaryotic DNA in bacteria using conventional plasmid-based vectors. One
      conventional plasmid vector (pGEM11), one conventional binary plasmid vector
      (pSLJ1711) and one conventional binary cosmid vector (pCLD04541) were
      investigated using the widely used BAC (pBeloBAC11 and pECBAC1) and BIBAC
      (BIBAC2) vectors as controls. The plasmid vector pGEM11 yielded clones ranging in
      insert sizes from 40 to 100 kb, whereas the two binary vectors pCLD04541 and
      pSLJ1711 yielded clones ranging in insert sizes from 40 to 310 kb. Analysis of
      the pCLD04541 and pSLJ1711 clones indicated that they had insert sizes and
      stabilities similar to the BACs and BIBACs. Our findings indicate that
      conventional plasmid-based vectors are capable of cloning and stably maintaining
      DNA fragments as large as BACs and PACs in bacteria. These results suggest that
      many existing plasmid-based vectors, including plant and animal transformation
      and expression binary vectors, could be directly used for cloning of very large
      eukaryotic DNA fragments. The pCLD04541 and pSLJ1711 clones were shown to be
      present at at least 4-5 copies/cell. The high stability of these clones indicates
      that stability of clones does not seem contingent on single-copy status. The
      insert sizes and the copy numbers of the pCLD04541 and pSLJ1711 clones indicate
      that Escherichia coli can stably maintain at least 1200 kb of foreign DNA per
      cell. These results provide a new conceptual and theoretical basis for
      development of improved and new vectors for large DNA fragment cloning and
      transformation. According to this discovery, we have established a system for
      large DNA fragment cloning in bacteria using the two binary vectors, with which
      several very large-insert DNA libraries have been developed.

PMID- 9776752
TI  - A peptide nucleic acid (PNA) is more rapidly internalized in cultured neurons
      when coupled to a retro-inverso delivery peptide. The antisense activity
      depresses the target mRNA and protein in magnocellular oxytocin neurons.
AB  - A peptide nucleic acid (PNA) antisense for the AUG translation initiation region
      of prepro-oxytocin mRNA was synthesized and coupled to a r etro-inverso peptide
      that is rapidly taken up by cells. This bioconjugate was internalized by cultured
      cerebral cortex neurons within minutes, according to the specific property of the
      vector peptide. The PNA alone also entered the cells, but more slowly. Cell
      viability was unaffected when the PNA concentrations were lower than 10 microM
      and incubation times less than for 24 h. Magnocellular neurons from the
      hypothalamic supraoptic nucleus, which produce oxytocin and vasopressin, were
      cultured in chemically defined medium. Both PNA and vector peptide-PNA depressed
      the amounts of the mRNA coding for prepro-oxytocin in these neurons. A scrambled
      PNA had no effect and the very cognate prepro-vasopressin mRNA was not affected.
      The antisense PNA also depressed the immunocytochemical signal for prepro
      oxytocin in this culture in a dose- and time-dependent manner. These results show
      that PNAs driven by the retro-inverso vector peptide are powerful antisense
      reagents for use on cells in culture.

PMID- 9776753
TI  - AbeI, a restriction endonuclease from Azotobacter beijerinckii, which recognizes
      the asymmetric heptanucleotide sequence 5'-CCTCAGC-3'(-5/-2).
AB  - A new restriction endonuclease Abe I has beenisolated from Azotobacter
      beijerinckii. This enzymerecognizes the asymmetric heptanucleotide sequence 5'
      CCTCAGC-3' and cleaves within it symmetrically at positions -5/-2 in the opposing
      strands, producing three base protruding 5'-ends.

PMID- 9776754
TI  - Targeting of nucleic acid junctions: addressing to a branch point an
      oligodeoxynucleotide conjugated with an intercalator.
AB  - It is possible to enhance targeting of a DNA stem flank domain with a
      complementary DNA when it is conjugated with diphenyl ether at the branch point.
      The nucleoside 2'-deoxy-5-methyl- N 4-(4-phenoxyphenyl)cytidine (5) was
      synthesized from thymidineby tritylation, acetylation, amination via 2,4, 6
      trimethylbenzenesulfonyl activation and subsequent de-protection. When a three
      way junction is formed with a bulged nucleoside 5 at the branch point, the
      thermal melting temperature was increased by 9 degreesC when compared with wild
      type DNA. When hybridizing to one of the flanks at a stem allowing coaxial
      stacking to the stem, modification at the branch point resulted in DeltaTm= 5.8
      degreesC. For targeting to RNA the results were more ambiguous. RNase H activity
      was observed in some cases when an intercalating aromatic ring was addressed at
      the branch point. RNase H activity was observed even for a short 7mer ODN.

PMID- 9776755
TI  - NMR solution structure of a DNA dodecamer containing single G.T mismatches.
AB  - The three-dimensional solution structure of the self-complementary DNA dodecamer
      (CGT_GACGT_TACG above GCAT_TGCAG_TGC] which contains the thermodynamically
      destabilizing [TG_A above AT_T] motif was determined using two-dimensional NMR
      spectroscopy and simulated annealing protocols. Relaxation matrix analysis
      methods were used to yield accurate NOE derived distance restraints. Scalar
      coupling constants for the sugar protons were determined by quantitative
      simulations of DQF-COSY cross-peaks and used to determine sugar pucker
      populations. Twenty refined structures starting from random geometries converged
      to an average pairwise root mean square deviation of 0.49 A. Back calculated NOEs
      give Rc and Rx factors of 0.38 and 0.088, respectively. The final structure shows
      that each of the single G@T mismatches form a wobble pair with two hydrogen bonds
      where the guanine projects into the minor groove and the thymine projects into
      the major groove. The incorporation of the destabilizing [TG_A above AT_T] motif
      has little effect on the backbone torsion angles and helical parameters compared
      to standard B-form duplexes, which may explain why G.T mismatches are among the
      most commonly observed in DNA. The structure shows that perturbations caused by a
      G.T mismatch extend only to its neighboring Watson-Crick base pair, thus
      providing a structural basis for the applicability of the nearest-neighbor model
      to the thermodynamics of internal G.T mismatches.

PMID- 9776756
TI  - Guanine is the target for direct ionisation damage in DNA, as detected using
      excision enzymes.
AB  - Exposure of an aqueous, aerated solution (pH 7) of a double-stranded DNA to 193
      nm light, of sufficient energy to ionise DNA, leads to selective, non-random
      modification at guanine in the form of frank single-strand break (ssb) and base
      modifications, revealed by treatment with either Escherichia coli
      formamidopyrimidine-DNA glycosylase (Fpg), Escherichia coli endonuclease III
      (Nth) or hot piperidine treatment. There is a similar neighbouring base sequence
      dependence for Fpg- and Nth-sensitive damage as that previously reported for both
      hot alkali-labile damage and prompt ssb. Low yields of photoproducts, namely
      pyrimidine dimers, are also revealed using the enzyme T4 endonuclease V (T4 endo
      V). Although irradiation of DNA with 193 nm light causes photoionisation of all
      the nucleic acid bases, these results indicate that guanine is the predominant
      site for localisation of the oxidative damage. These findings are consistent with
      migration of the radical cation to 'target' damage at guanine sites.

PMID- 9776757
TI  - Direct laser trapping of single DNA molecules in the globular state.
AB  - A sharply focused laser is able to trap small particles at the laser focal point
      due to the difference in refractive index of the particles and that of the
      surrounding medium. This technique, called laser trapping, can be used to
      manipulate animal or bacterial cells without any contact and has been widely
      applied in biological research. However, it has been difficult to trap biological
      macromolecules such as DNA molecules, because these molecules give a low
      difference in refractive index and cannot overcome Brownian motion. DNA molecules
      can be transformed to a condensed globular state. This transformation results in
      a higher refractive index of DNA due to its increased density. We demonstrate in
      this paper that a single DNA molecule can be optically trapped using a Nd:YAG
      laser (1064 nm wavelength) upon transformation from the coiled state to the
      globular state.

PMID- 9776758
TI  - Random insertion of GFP into the cAMP-dependent protein kinase regulatory subunit
      from Dictyostelium discoideum.
AB  - The green fluorescent protein (GFP) is currently being used for diverse cellular
      biology approaches, mainly as a protein tag or to monitor gene expression.
      Recently it has been shown that GFP can also be used to monitor the activation of
      second messenger pathways by the use of fluorescence resonance energy transfer
      (FRET) between two different GFP mutants fused to a Ca2+sensor. We show here that
      GFP fusions can also be used to obtain information on regions essential for
      protein function. As FRET requires the two GFPs to be very close, N- or C
      terminal fusion proteins will not generally produce FRET between two interacting
      proteins. In order to increase the probability of FRET, we decided to study the
      effect of random insertion of two GFP mutants into a protein of interest. We
      describe here a methodology for random insertion of GFP into the cAMP-dependent
      protein kinase regulatory subunit using a bacterial expression vector. The
      selection and analysis of 120 green fluorescent colonies revealed that the
      insertions were distributed throughout the R coding region. 14 R/GFP fusion
      proteins were partially purified and characterized for cAMP binding, fluorescence
      and ability to inhibit PKA catalytic activity. This study reveals that GFP
      insertion only moderately disturbed the overall folding of the protein or the
      proper folding of another domain of the protein, as tested by cAMP binding
      capacity. Furthermore, three R subunits out of 14, which harbour a GFP inserted
      in the cAMP binding site B, inhibit PKA catalytic subunit in a cAMP-dependent
      manner. Random insertion of GFP within the R subunit sets the path to develop two
      component FRET with the C subunit.

PMID- 9776759
TI  - Human mitochondrial uracil-DNA glycosylase preform (UNG1) is processed to two
      forms one of which is resistant to inhibition by AP sites.
AB  - The preform of human mitochondrial uracil-DNA glycosylase (UNG1) contains 35 N
      terminal residues required for mitochondrial targeting. We have examined
      processing of human UNG1 expressed in insect cells and processing in vitro by
      human mitochondrial extracts . In insect cells we detected a major processed form
      lacking 29 of the 35 unique N-terminal residues (UNG1Delta29, 31 kDa) and two
      minor forms lacking the 75 and 77 N-terminal residues, respectively (UNG1Delta75
      and UNG1Delta77, 26 kDa). Purified UNG1Delta29 was effectively cleaved in vitro
      to a fully active 26 kDa form by human mitochondrial extracts. Furthermore,
      endogenous forms of 31 and 26 kDa were also observed in HeLa mitochondrial
      extracts. The sequences at the cleavage sites, as identified by peptide
      sequencing, were compatible with the known specificity of mitochondrial
      processing peptidase (MPP). However, in vitro cleavage of UNG1Delta29 by
      mitochondrial extracts did not require divalent cations and was stimulated by
      EDTA, indicating the involvement of a processing peptidase distinct from MPP at
      the second site. Interestingly, while UNG1Delta29 generally has the typical
      properties reported for other uracil-DNA glycosylases, it is not inhibited by
      apurinic/apyrimidinic sites. Our results indicate that the preform of human
      mitochondrial uracil-DNA glycosylase is processed to distinctly different forms
      lacking 29 or 75/77 N-terminal residues, respectively.

PMID- 9776760
TI  - Comparison of murine Supt4h and a nearly identical expressed, processed gene:
      evidence of sequence conservation through gene conversion extending into the
      untranslated regions.
AB  - We show herein the transcription of a processed gene that originated from a
      spliced transcript. Recently, we isolated the human and murine homologues of the
      yeast chromatin protein, SPT4. The Supt4h gene is spliced normally from five
      exons encoded by chromosome 11. Here we show that a related sequence on
      chromosome 10 encodes Supt4h2, a processed intronless gene (with a polyA tail and
      a tandemly-duplicated 13 bp insertion site in the genome) with a different 5'
      control region. Both the spliced gene, Supt4h , and the processed gene, Supt4h2 ,
      are expressed in each of four tissues we examined. Supt4h2 encodes a 117 amino
      acid protein nearly identical to the Supt4h gene product with only one amino acid
      difference, indicating extreme conservation of this expressed processed gene with
      the spliced gene over evolutionary time. This illustrates another potential
      complexity of the mammalian genome, i.e. the use of a processed gene under the
      control of a different promoter region than the spliced gene.

PMID- 9776761
TI  - A specific RNA-protein interaction at yeast polyadenylation efficiency elements.
AB  - The specific RNA-protein interactions responsible for the production of mature 3'
      ends of eukaryotic mRNAs are not well understood. Sequence elements at the 3'
      ends of yeast genes have been identified that specify the position of the poly(A)
      site and the efficiency of polyadenylation. To provide additional insights into
      the interaction between important sequences that direct 3'-end formation in vivo
      and nuclear proteins, we utilized gel mobility shift assays and UV-crosslinking
      studies. The data indicate that a protein, with an apparent molecular weight of
      80 kDa, interacts specifically with pre-mRNA at the (UA)3efficiency element.
      Although the interaction is specific, it can be competed by RNA sequences that do
      not contain the same type of efficiency element; that is, a sequence lacking a
      (UA)3repeat. This result implies that the protein binding site is flexible. Using
      immunoprecipitation techniques, the protein has been identified as Hrp1, a
      heteronuclear RNA binding protein. The role of Hrp1p in 3'-end formation
      including RNA processing and transcription termination is addressed.

PMID- 9776763
TI  - Incorporation of terminal phosphorothioates into oligonucleotides.
AB  - Considerable effort has been directed towards studying the structure and function
      of oligonucleotides and several approaches rely on the attachment of reporter
      groups to oligonucleotides. We report here the introduction of 3'- and 5'
      terminal phosphorothioates into heptameric oligonucleotides and their post
      synthetic modification with several reporter groups. The synthesis of terminal
      phosphorothioates is based on the coupling of a ribonucleoside phosphoramidite at
      the first or last nucleotide, respectively, which, after sulphurization, is
      removed by sequential oxidation of the vicinal hydroxyl groups and then beta
      elimination. Product formation is of the order of 95%. The ratio of
      phosphorothioate- versus phosphate-terminated oligodeoxynucleotides as analysed
      by electrophoresis on a Hg2+gel is in general 85/15. Examples for the reactivity
      of the terminal phosphorothioates for conjugation with cholesterol, bimane and
      for sulphydryl exchange are described.

PMID- 9776762
TI  - Enhanced high density oligonucleotide array-based sequence analysis using
      modified nucleoside triphosphates.
AB  - Pairs of high density oligonucleotide arrays (DNA chips) consisting of >96 000
      oligonucleotides were designed to screen the entire 5.53 kb coding region of the
      hereditary breast and ovarian cancer BRCA1 gene for all possible sequence changes
      in the homozygous and heterozygous states. Single-stranded RNA targets were
      generated by PCR amplification of individual BRCA1 exons using primers containing
      T3 and T7RNA polymerase promoter tails followed by in vitro transcription and
      partial fragmentation reactions. Fluorescent hybridization signals from targets
      containing the four natural bases to >5592 different fully complementary 25mer
      oligonucleotide probes on the chip varied over two orders of magnitude. To
      examine the thermodynamic contribution of rU.dA and rA.dT target.probe base pairs
      to this variability, modified uridine [5-methyluridine and 5-(1-propynyl)
      uridine)] and modified adenosine (2,6-diaminopurine riboside) 5'-triphosphates
      were incorporated into BRCA1 targets. Hybridization specificity was assessed
      based upon hybridization signals from >33 200 probes containing centrally
      localized single base pair mismatches relative to target sequence. Targets
      containing 5-methyluridine displayed promising localized enhancements in
      hybridization signal, especially in pyrimidine-rich target tracts, while
      maintaining single nucleotide mismatch hybridization specificities comparable
      with those of unmodified targets.

PMID- 9776764
TI  - Growth-regulated antisense transcription of the mouse thymidine kinase gene.
AB  - The expression of the salvage pathway enzyme thymidine kinase (TK) is very low in
      resting mammalian cells, but increases dramatically when growth-stimulated cells
      enter S phase. The 30-fold rise in TK mRNA levels in response to growth factors
      is due to a well-characterized transcriptional activation and less defined post
      transcriptional mechanisms. A minigene containing the murine TK promoter and the
      TK cDNA showed a 3-fold increase in TK mRNA levels after growth induction in
      stably transfected mouse TK-deficient L fibroblasts. Introduction of the first
      three TK introns resulted in a 10-fold regulation of TK expression which was
      predominantly due to repressed TK mRNA levels in serum-deprived cells. Removal of
      intron 3 from this construct or replacement of the TK promoter by a constitutive
      SV40 promoter led to a reduced, but still significant increase in TK mRNA levels
      during the onset of proliferation. These results indicate that both the TK
      promoter and specific TK introns contribute independently to the growth-dependent
      regulation of TK mRNA expression. To examine the regulatory mechanisms in more
      detail we analyzed TK transcription rates and steady-state levels of nuclear
      transcripts from an SV40 promoter-driven minigene that contains introns 2 and 3
      of the TK gene. Using a set of single-stranded probes we detected TK-specific
      antisense transcription that was up-regulated in resting cells. Similarly,
      antisense transcription of the endogenous TK gene in Swiss 3T3 cells rose during
      serum deprivation while sense transcription was regulated in the opposite way.
      Luciferase reporter assays revealed the presence of a putative antisense promoter
      in intron 3 of the murine TK gene. These results suggest a negative role for
      intron-dependent antisense transcription in the regulation of TK mRNA expression
      in mouse fibroblasts.

PMID- 9776765
TI  - Circular dichroism and UV melting studies on formation of an intramolecular
      triplex containing parallel T*A:T and G*G:C triplets: netropsin complexation with
      the triplex.
AB  - We have used circular dichroism and UV absorption spectroscopy to characterize
      the formation and melting behaviour of an intramolecular DNA triple helix
      containing parallel T*A:T and G*G:C triplets. Our approach to induce and to
      stabilize a parallel triplex involves the oligonucleotide 5'-d(G4A4G4[T4]C4T4C4
      [T4]G4T4G4) ([T4] represents a stretch of four thymine residues). In a 10 mM
      sodium cacodylate, 0.2 mM disodium EDTA (pH 7) buffer, we have shown the
      following significant results. (i) While in the absence of MgCl2 this
      oligonucleotide adopts an intramolecular hairpin duplex structure prolonged by
      the single strand extremity 5'-d([T4]G4T4G4), the presence of millimolar
      concentrations of MgCl2generates an intramolecular triplex (via double hairpin
      formation). (ii) In contrast to the antiparallel triplex formed by the
      oligonucleotide 5'-d(G4T4G4[T4]G4A4G4[T4]C4T4C4), the parallel triplex melts in a
      biphasic manner (a triplex to duplex transition followed by a duplex to coil
      transition) and is less stable than the antiparallel one. The enthalpy change
      associated with triplex formation (-37 kcal/mol) is approximately half that of
      duplex formation (-81 kcal/mol). (iii) The parallel triple helix is disrupted by
      increasing the concentration of KCl(>10 mM), whereas, under the same conditions,
      the antiparallel triplex remains stable. (iv) Netropsin, a natural DNA minor
      groove-binding ligand, binds to the central site A4/T4of the duplex or triplex in
      an equimolar stoichiometry. Its association constant K is smaller for the
      parallel triplex ( approximately 1 x 10(7) M-1) than for the antiparallel one (
      approximately 1 x 10(8) M-1). In contrast to the antiparallel structure,
      netropsin binding has no apparent effect on thermal stability of the parallel
      triple helix.

PMID- 9776766
TI  - A formula for thermal stability (Tm) prediction of PNA/DNA duplexes.
AB  - An empirical formula for thermal stability (T m) prediction of PNA/DNA duplexes
      has been derived. The model is based on the T m as calculated for the
      corresponding DNA/DNA duplex employing a nearest neighbour approach, by including
      terms for the pyrimidine content and length of the PNA to take into account the
      increased thermostability of PNA/DNA hybrids and the asymmetry of the PNA-DNA
      heteroduplex. The predictive power of the T m prediction formula was challenged
      with an independent data set not used for model building. The T m of >90% of the
      sequences was predicted within 5 K; 98% of the predicted T ms differ by not more
      than 10 K from the experimentally determined T m.

PMID- 9776767
TI  - A method for global protein expression and antibody screening on high-density
      filters of an arrayed cDNA library.
AB  - We have developed a technique to establish catalogues of protein products of
      arrayed cDNA clones identified by DNA hybridisation or sequencing. A human fetal
      brain cDNA library was directionally cloned in a bacterial vector that allows
      IPTG-inducible expression of His6-tagged fusion proteins. Using robot technology,
      the library was arrayed in microtitre plates and gridded onto high-density in
      situ filters. A monoclonal antibody recognising the N-terminal RGSH6sequence of
      expressed proteins (RGS.His antibody, Qiagen) detected 20% of the library as
      putative expression clones. Two example genes, GAPDH and HSP90alpha, were
      identified on high-density filters using DNA probes and antibodies against their
      proteins.

PMID- 9776768
TI  - Urea improves efficiency of bisulphite-mediated sequencing of 5'-methylcytosine
      in genomic DNA.
AB  - The detection of 5'-methylcytosine by the bisulphite-mediated genomic sequencing
      method has considerably aided study of the role of methylation in areas such as X
      chromosome inactivation, genomic imprinting and cancer research. However on
      occasion difficulty has been experienced in obtaining complete conversion of
      cytosine to uracil in regions of the target DNA. We report here a simple
      improvement to the method involving addition of urea to the bisulphite reaction,
      a step which greatly improves the reaction efficiency, presumably by maintaining
      the target DNA in single stranded form, thereby allowing complete and reliable
      conversion.

PMID- 9776769
TI  - Yeast artificial chromosome segregation from host chromosomes with similar
      lengths.
AB  - We propose a new method for segregation of yeast artificial chromosomes (YACs)
      from endogenous yeast chromosomes with similar lengths. The method is based on
      recently developed PNA-assisted rare cleavage (PARC) of genomic DNA. We apply the
      PARC procedure to YAC-containing samples of yeast DNA in such a way that host
      chromosomes, which electrophoretically comigrate with the chosen YACs, are
      selectively digested while YACs remain intact. These data demonstrate that a pool
      of appropriate PNAs can be used as an efficient tool for the PARC-based isolation
      of intact purified YACs directly from the host cells.

PMID- 9776770
TI  - Primer specific and mispair extension analysis (PSMEA) as a simple approach to
      fast genotyping.
AB  - A simple method, primer specific and mispair extension analysis (PSMEA) with pfu
      DNA polymerase was developed for genotyping. PSMEA is based on the unique
      properties of 3'-->5' exonuclease proofreading activity. In the presence of an
      incomplete set of dNTPs, pfu was found to be extremely discriminative in
      nucleotide incorporation and proofreading at the initiation step of DNA
      synthesis, completely preventing primer extension when mispair(s) are found
      adjacent to the 3'-end of the primer. This has allowed us to accurately detect
      nucleotide variations, deletions and insertions for fast genotyping.

PMID- 9776771
TI  - Monitoring and mass budget for mercury in the everglades nutrient removal project
AB  - The Everglades Nutrient Removal Project (ENRP) is a 1,545-ha prototype wetland
      constructed to test a larger system of stormwater-treatment areas that is being
      used to remove agricultural nutrients and help restore the remnant Everglades.
      Concerns that the ENRP may lead to mercury bioaccumulation as observed in other
      newly created reservoirs resulted in an effort to construct a mercury mass budget
      and measure bioaccumulation in aquatic organisms. For the first 2 years of
      operation, total mercury (THg) and methylmercury (MeHg) concentrations in water
      decreased significantly a short distance into the ENRP, probably through particle
      settling. During both years, THg concentrations in largemouth bass were about 0.1
      &mgr;g/g throughout the ENRP while the adjacent Water Conservation Area bass were
      at or above the state health advisory level of 0.5 &mgr;g/g. THg levels in
      mosquitofish were lower than levels found in bass, and mosquitofish mercury
      concentrations in the interior of the ENRP were significantly lower than the
      inflow and outflow sites. The major THg pool was the sediment while less than 1%
      the total mass was stored in vegetation, water, and fish. The major MeHg pool
      also was the sediment but vegetation, water, and fish were significant fractions.
      Mass budget estimates showed the inflow pump and rainfall to be the major sources
      of THg, while the outflow pump was the major output. The inflow pump was the
      major source of MeHg while the outflow pump was the major output. Evasion of
      elemental mercury estimated by the stagnant-film model indicated a minor loss,
      but field measurements over cattails suggested that evasion may be the major
      pathway. When all inputs and outputs were considered, the ENRP removed about 70%
      of the THg and MeHg masses in the first 2 years of operation.

PMID- 9776772
TI  - Organotin compounds in water, sediment, and biological samples from the port of
      osaka, japan 
AB  - Butyltin (Bts) and phenyltin compounds (Pts) were measured in water, sediment,
      plankton, and mussels collected from eight stations in the harbor area of the
      Port of Osaka in 1996, and were compared with those of Otsuchi Bay. The levels of
      tributyltin (TBT) compounds in all samples from the Port of Osaka were slightly
      high in marinas and mooring areas of small and medium-hull vessels. Of total Bts,
      the ratio of TBT was under 50% in water and was dominant in sediment, plankton,
      and mussels. Triphenyltin (TPT) compounds in water were not detected. TPT was
      present at lower levels than TBT in sediment, plankton, and mussels. Of total
      Pts, monophenyltin (MPT) compounds and diphenyltin (DPT) compounds represented a
      high proportion in sediment, while TPT was dominant in plankton and mussels. The
      concentrations of TBT in water from the Port of Osaka were lower than those from
      Otsuchi Bay, however TBT concentrations in sediment, plankton, and mussels from
      the Port of Osaka were higher than those from Otsuchi Bay. The difference of TBT
      concentration among stations in the Port of Osaka was slight. In contrast, the
      levels of TBT in Otsuchi Bay were markedly higher at a station near the shipyard.
      Though TPT in water from the Port of Osaka was not detected, trace amounts of TPT
      was found in seawater from Otsuchi Bay. The levels and detected frequencies of
      TPT in sediment, plankton, and mussels from the Port of Osaka were lower than in
      those from Otsuchi Bay. The partition coefficients of Bts to sediment, plankton,
      and mussels from the Port of Osaka were higher than those of dibutyltin (DBT)
      compounds and MBT and those of TBT to plankton and mussels were higher than those
      in sediment. The partition coefficients of TBT to sediment and biological samples
      from the Port of Osaka were higher level than those in Otsuchi Bay.

PMID- 9776773
TI  - Selection of an aquatic indicator species to monitor organic contaminants in
      trophically simple lotic food webs 
AB  - A four-step procedure was used to identify an aquatic macroinvertebrate with
      which to monitor organic contaminant burdens in trophically simple lake food webs
      of Alberta, Canada. We identified leeches (Oligochaeta: Hirudinea) as the
      potential indicator assemblage (Step 1), and then documented their abundance and
      distribution in 16 lakes to identify a species-level bioindicator (Step 2). The
      latter two steps involved identifying the number and level of organic
      contaminants within the indicator species (Step 3) and a comparison with other
      taxa within the food web (Step 4). The majority of lakes within the watershed
      contained seven to nine leech species with individuals of Nephelopsis obscura
      being one of the most abundant and widely distributed species that is
      sufficiently large to allow for rapid collection of sufficient biomass for
      organic contaminant analyses. Concentrations of organic contaminants in leeches
      from 22 sites and in sediments (two lakes) within the watershed were low, and in
      the majority of cases less than analytical detection levels (i.e., 0.05 &mgr;g/kg
      wet weight). Nevertheless, leech tissues contained trace amounts of a fungicide
      (i.e., hexachlorobenzene) and four pesticides including: pp'-DDE, pp'-DDD,
      representing intermediate and final breakdown products of pp'-DDT, a-HCH (i.e.,
      hexachlorocyclohexane) and g-HCH (Lindane). Concentrations of these contaminants
      did not differ significantly between leeches collected from lakes within a
      national park compared to areas outside the park that may have been more
      vulnerable to loadings of contaminants from industrial and agricultural sources.
      Lastly, we compared organic contaminant concentrations in N. obscura with
      Gammarus lacustris and Brook's stickleback, Culaea inconstans (Gasterosteidae).
      Organic contaminant concentrations in N. obscura were similar or higher than
      those present in G. lacustris and C. inconstans. Eight organic contaminants were
      found in N. obscura, whereas, C. inconstans and G. lacustris contained only three
      and four, respectively. The fact that N. obscura typically contained higher
      concentrations and greater numbers of detectable compounds suggest that it is a
      suitable indicator of organic contamination. While current levels of organic
      contaminants in the Beaver Hills watershed are low, despite the intense
      agriculture and industrial activities, they should be monitored to act as an
      early warning indicator of ecosystem degradation.

PMID- 9776775
TI  - Environmental effects of sodium Acetate/Formate deicer, ice sheartrade mark 
AB  - The environmental impacts of Ice Sheartrade mark, an alternative highway deicer,
      have been evaluated using standard laboratory tests; biochemical oxygen demand
      (BOD) tests, chemical oxygen demand (COD) tests, acute rainbow trout bioassays,
      and phytotoxicity tests were used. Ice Shear consists of equimolar sodium acetate
      and sodium formate. The organic matter of the deicer can be readily degraded
      microbiologically in the natural environment with a slow rate of degradation at
      lower temperatures but an increased rate at higher temperatures. At elevated
      temperatures, highway runoffs of the deicer may reduce the level of dissolved
      oxygen in the receiving waters to cause an adverse impact. However, the apparent
      activation energy calculated for the BOD rate of Ice Shear is low (8.78 kcal mole
      1), indicating that the temperature variation may not significantly influence the
      biodegradation of the deicer compound. Ice Shear appears relatively harmless to
      aquatic animals, showing a high 96-h LC50 value (16.1 g/L) derived for rainbow
      trout (Oncorhynchus mykiss). Ice Shear causes minimal toxicity to representative
      roadside vegetation; herbaceous (e.g., sunflowers, beans, and lettuce) and woody
      (e.g., pine seedlings) plants. Rather, the deicer at low concentrations (less
      than 2 g/kg soil) seems to work as a fertilizer, promoting the yield of biomass.
      The test results indicate that Ice Shear poses minimal environmental disturbance
      in both aquatic and terrestrial ecosystems.

PMID- 9776774
TI  - Sediment toxicity evaluation for hexachlorobenzene: spiked sediment tests with
      Leptocheirus plumulosus, Hyalella azteca, and Chironomus tentans.
AB  - Hexachlorobenzene (HCB) is a hydrophobic organic chemical that has shown a lack
      of toxicity in aquatic tests at concentrations up to and exceeding the solubility
      limit. The equilibrium partitioning approach to deriving sediment quality
      benchmarks, which assumes that toxicity can be predicted based on contaminant
      concentrations in interstitial water, predicts that HCB will not produce direct
      toxicity to benthic invertebrates as a sediment contaminant. However, the
      potential for toxicity due to direct exposure to sediment-adsorbed HCB has not
      been thoroughly established. This study evaluated the survival and growth of the
      estuarine amphipod Leptocheirus plumulosus, the freshwater amphipod Hyalella
      azteca, and the midge Chironomus tentans (freshwater) following 10-day exposure
      to sediment spiked with a range of HCB concentrations. H. azteca was tested under
      both freshwater and estuarine (10 ppt salinity) conditions. No significant
      toxicity was observed for any test species at the highest test concentration (60
      mg/kg normalized to 1% organic carbon). Minimum detectable differences were less
      than or equal to 20% for three of eight test endpoints. The observed results add
      to the available weight of evidence indicating a limited potential for HCB
      related sediment toxicity to benthic invertebrates.

PMID- 9776776
TI  - Interference by carbohydrate substrates, flavonoids, and monosaccharide
      derivatives on bacterial beta-D-glucuronidase assays.
AB  - Most commercially available test kits for water and foodstuffs use beta
      galactosidase activity for coliforms and beta-glucuronidase activity for
      Escherichia coli. We tested the effects on the beta-glucuronidase activity of E.
      coli W3110 of substances usually present in foods and several synthetic
      pharmaceutical compounds. Thirteen substances were tested: three carbohydrates,
      four flavonoids, five monosaccharide derivatives, and dimethyl sulphoxide. In a
      minimum medium without any other carbon source, glucose (0.1 mM), quercetin (0.1
      mM), silymarin (10 mg/L), D-gluconic acid (0.01 mM), D-gluconic acid lactone
      (0.01 mM), isopropyl-beta-D-thiogalacto pyranoside (1 mM), p-nitrophenyl beta-D
      glucuronide (1 mM), and DMSO (1 M) completely inhibited E. coli glucuronidase
      activity at the above concentrations. However, the following compounds stimulated
      E. coli glucuronidase activity within the ranges of concentrations shown: glucose
      (0.0001-0.01 mM), lactose and sucrose (>0.1 mM), D-saccharic acid 1,4 lactone
      (0.0001-0.1 mM), p-nitrophenyl beta-D-glucuronide (0.001-0.01 mM) and DMSO (2-500
      mM). In a rich culture medium that contained other carbon sources (lauryl
      tryptose broth) E. coli glucuronidase activity in the presence of the extra
      nutrients was unaffected by the test substances and therefore, under normal
      conditions in water or foods, they should not interfere with E. coli assays based
      on measurements of beta-glucuronidase activity.

PMID- 9776777
TI  - Trace metals and variations of antioxidant enzymes in Arctic bivalve populations.
AB  - In the framework of an INTAS project, arctic populations of the clam Macoma
      balthica were collected from seven stations (Mezen, Khaypudyr, Pechora 3, Pechora
      5, Dvina, Keret 1, and Keret 2) in the White Sea and Pechora Sea. The main
      objectives of this research were to define baseline concentrations of trace
      metals (As, Cd, Cr, Cu, Fe, Mn, Pb, Zn) in M. balthica and to evaluate
      antioxidant responses as biomarkers of anthropogenic stress in these organisms.
      The antioxidant parameters examined included the levels of glutathione and the
      activities of several glutathione-dependent and antioxidant enzymes: glyoxalase I
      and glyoxalase II (EC 4.4.1.5 and EC 3.1.2.6), glutathione S-transferases (EC
      2.5.1.18), glutathione reductase (EC 1.6.4.2), glutathione peroxidases
      (EC1.11.1.9 and EC 2.5.1.18, respectively, for Se-dependent and Se-independent
      forms), superoxide dismutase (SOD, EC 1.15.1.1), and catalase (EC 1.11.1.6).
      Organisms revealed enhanced concentrations of lead in both Keret stations,
      Khaypudyr, and Mezen, and high levels of copper in Keret and cadmium in
      Khaypudyr. At the biochemical level, organisms from Pechora 3, Pechora 5, and
      Dvina were not statistically different, whereas those from Mezen and Khaypudyr
      exhibited higher activities of superoxide dismutase, glutathione peroxidase, and
      glyoxalase II. Catalase levels were lower in Mezen and Khaypudyr. More
      heterogeneous were the responses of glyoxalase I and glutathione S-transferases,
      while no significant differences among the stations were observed for glutathione
      reductase. Multiple regression analyses revealed significant positive
      relationships between the main antioxidant enzymes (glutathione peroxidases,
      superoxide dismutase, glyoxalase I, and glyoxalase II), and confirmed the
      exception of catalase, which, when significant, was negatively correlated with
      the other parameters. The results support the suitability of antioxidant
      responses as biomarkers of pollutant exposure and/or toxicity for arctic
      biomonitoring programs even though only moderately polluted sites were sampled.

PMID- 9776778
TI  - Glutathione, glutathione-related enzymes, and catalase activities in the
      earthworm Eisenia fetida andrei.
AB  - The aim of this work was to provide basic data on the antioxidant defences in the
      annelid Eisenia fetida andrei (E. f. a.). Methods for measurement of three
      antioxidant enzymes-catalase (CAT), glutathione peroxidase (GPX), and glutathione
      reductase (GR)-and of glutathione-S-transferase (GST) were optimized. GPX
      activity differed according to the substrate used: cumene hydroperoxide (CUOOH)
      or hydrogen peroxide (H2O2). The effects on the enzyme activities of storage up
      to 2 months at -80 degrees C, -20 degrees C, and +4 degrees C were evaluated. The
      subcellular distribution (in cytosol, mitochondrial, and microsomal fractions)
      was examined. The properties and subcellular distribution of the enzymes and
      glutathione were also characterized in dissected tissues and body fluids. The GR
      activity decreased at -80 degrees C and was the only one not stable at this
      temperature. The four enzymes were localized mainly in the cytosolic fraction.
      CAT distribution was unusual as it was not associated with peroxisomes, its
      properties being consistent with a catalase-peroxidase, rather than a true
      catalase. However, this result could also be an artifact linked to the use of an
      inappropriate method to obtain the fractions. Our observations indicate the
      presence of a distinct cytosolic selenium-dependent GPX (Se-GPX), and of a
      possible microsomal Se-GPX. A strong non-Se-GPX activity was measured in the CF
      and CL, which could be linked to the peroxidase activity of fetidins secreted by
      coelomocytes and with the ROS production of these cells. This study seems to
      indicate that E. f. a. is well equipped for the metabolism of electrophilic and
      pro-oxidants through glutathione.

PMID- 9776779
TI  - Effects of boron and nitrate on hatching success of amphibian eggs.
AB  - As part of a land-application wastewater disposal system in central Pennsylvania,
      vernal ponds are commonly exposed to wastewater effluent containing high levels
      of boron and nitrate. We examined the individual effects of these compounds on
      the eggs of amphibians breeding in these ponds. Wood frog (Rana sylvatica),
      Jefferson salamander (Ambystoma jeffersonianum), spotted salamander (A.
      maculatum), and American toad (Bufo americanus) eggs were exposed to boron (0,
      50, and 100 mg L-1) and nitrate (0, 10, 25, and 40 mg L-1) under laboratory
      conditions. There was no difference in the hatching success or proportion of
      deformed larvae among the four nitrate levels in any of the species. High boron
      concentrations reduced the hatching success of B. americanus and produced more
      deformed offspring in R. sylvatica, A. jeffersonianum, and A. maculatum. Deformed
      R. sylvatica and A. jeffersonianum hatchlings displayed a "curling defect" in
      which the larvae had a crescent body shape and expressed difficulty in swimming.
      A. maculatum larvae from high boron treatments displayed a different abnormality,
      possibly because of longer times to hatching, characterized by a swelling of the
      thoracic region and altered gill morphology. Although the concentrations of boron
      and nitrate tested were within the range measured in wastewater effluent, maximum
      levels of boron and nitrate in breeding ponds were only 1.5 mg L-1 and 26.7 mg L
      1 respectively, likely due to rainwater dilution and biological and chemical
      processes reducing the levels of these compounds in vernal ponds. Nonetheless,
      these studies are the first to examine the effects of boron and nitrate on
      amphibian egg hatching success, and to demonstrate that elevated boron
      concentrations can detrimentally affect the development of amphibian embryos.

PMID- 9776780
TI  - Contaminants in ospreys from the Pacific Northwest: I. Trends and patterns in
      polychlorinated dibenzo-p-dioxins and -dibenzofurans in eggs and plasma.
AB  - Osprey (Pandion haliaetus) eggs were collected from 1991 to 1997 at nests (n =
      121) upstream and downstream of bleached kraft pulp mills and at reference sites
      in the Fraser and Columbia River drainage systems of British Columbia,
      Washington, and Oregon. Blood samples were collected from nestling ospreys during
      the 1992 breeding season on the Thompson River. Samples were analyzed for
      polychlorinated dibenzo-p-dioxins (PCDDs) and -dibenzofurans (PCDFs). Mean
      concentrations of 2,3,7,8-TCDD were significantly higher in eggs collected in
      1991 at downstream compared to upstream nests near pulp mills at Kamloops and
      Castlegar, British Columbia. There were no significant temporal trends in 2,3,7,8
      TCDD, -TCDF or other measured compounds at a sample of nests monitored between
      1991 and 1994 downstream of the Castlegar pulp mill, despite changes in bleaching
      technology (CIO2 substitution). However, by 1997 concentrations of 2, 3,7,8-TCDD
      and -TCDF were significantly lower than previous years in nests sampled
      downstream at both Castlegar and Kamloops. An unusual pattern of higher
      chlorinated PCDDs and PCDFs was found in many of the osprey eggs collected in
      this study, and considerable individual variation in the pattern existed among
      eggs from the same site. For example, eggs from four different nests at one study
      area (Quesnel) on the Fraser River had concentrations of 1,2,3,4,6,7,8-HpCDD
      ranging from <1 to 1,100 ng/kg and OCDD from <1 to 7,000 ng/kg wet weight. Higher
      mean concentrations of HpCDD and OCDD were found in eggs from the Thompson River,
      a tributary of the Fraser, compared to the Columbia River, and concentrations
      were generally higher at nests upstream of pulp mills. In plasma samples,
      1,2,3,4,6,7,8-HpCDD and OCDD were the main compounds detected, with no
      significant differences measured between samples upstream versus downstream or
      earlier versus later in the breeding season. Use of chlorophenolic wood
      preservatives by lumber processors was considered the main source of higher
      chlorinated PCDD/Fs throughout the systems, based on patterns of trace PCDFs in
      eggs and significant correlations between egg concentrations of pentachlorophenol
      and both HpCDD (r = 0.891, p < 0.01) and OCDD (r = 0.870, p < 0.01).

PMID- 9776781
TI  - Influence of heavy metal exposure during different phases of the ontogeny on the
      development of pied flycatchers, Ficedula hypoleuca, in natural populations.

PMID- 9776782
TI  - Distribution of 14 elements in tissues and organs of oceanic seabirds.
AB  - The concentrations of 14 trace elements (Li, V, Mn, Co, Cu, Zn, Se, Rb, Sr, Ag,
      Cd, Cs, Pb, and Hg) were determined in tissues and organs of three species and in
      the liver of 11 species of seabirds. Comparatively high concentrations of Li, Co,
      Sr, and V were found in the femur. Cd, Se, Cu, and Mn concentrations were
      relatively higher in the kidney than in other tissues and organs. Rb, Cs, and Pb
      concentrations were rather uniform among tissues. Concentrations of essential
      elements such as Mn, Cu, and Co were comparable among seabird species, except
      high Cu concentrations in northern giant petrel. Among nonessential elements,
      concentrations of Cd and Hg were variable according to seabird species. Pb levels
      were low in all the species. High Se levels (100 microg/g dry weight) were found
      in the liver of black-footed albatross and grey petrel. There were significant
      positive correlations between Se and Cd concentrations in three species and
      between Se and Hg in black-footed albatross, suggesting that Se has an
      antagonistic action on the toxic effects of Cd and Hg. Concentrations of Li, V,
      Ag, and Cs were usually low (less than 1 microg/g dry weight).

PMID- 9776783
TI  - Lack of developmental and reproductive toxicity of 2,3,3',4, 4'
      pentachlorobiphenyl (PCB 105) in ring-necked pheasants.
AB  - Mono-ortho PCBs are global contaminants of wildlife with the potential to produce
      toxicity by an aryl hydrocarbon receptor (AhR)-mediated mechanism. To determine
      the potency of 2,3,3',4, 4'-pentachlorobiphenyl (PCB 105) for producing
      reproductive and developmental toxicity, adult ring-necked pheasant hens
      (Phasianus colchicus) were orally dosed with 0, 0.06, 0.6, or 6 mg PCB 105/kg
      hen/week for 10 weeks to achieve cumulative doses of 0, 0.6, 6, or 60 mg PCB
      105/kg hen after which hens were bred with untreated roosters once per week for 8
      weeks. Except at week 6 of the egg-laying period when cumulative egg production
      in the 6 mg PCB 105/kg hen group was greater than controls, fertilized egg
      production was not significantly different between treatment groups. Embryo
      mortality and chick mortality were not significantly different between treatment
      groups. Total body and heart weights of all chicks 1 day posthatch (dph) were not
      different between groups, however, liver weights of chicks from the 60 mg/kg
      treatment group were greater than controls at 1 dph. The first chick to hatch
      from each hen was reared to 21 dph and among these birds, the total body, liver,
      and heart weights were not different between groups. There were no dose-related
      malformations of the beak or limbs, and no signs of subcutaneous edema, ascites,
      or pericardial edema in chicks at 1 or 21 dph. Hepatic microsomal monooxygenase
      activities [ethoxyresorufin-O-dealkylase (EROD), benzyloxyresorufin-O-dealkylase
      (BROD), and methyloxyresorufin-O-dealkylase (MROD)] were significantly elevated
      in chicks at 1 dph from hens given a cumulative PCB 105 dose of 6 mg/kg and in
      chicks at 21 dph from hens given a cumulative PCB dose of 60 mg/kg. These results
      indicate that a cumulative PCB 105 dose up to 60 mg/kg hen does not decrease the
      production of fertilized eggs or increase embryo or chick mortality in ring
      necked pheasants, but does increase chick hepatic monooxygenase activity.

PMID- 9776784
TI  - Studies of bioaccumulation and biotransformation of PCBs in mustelids based on
      concentration and congener patterns in predators and preys.
AB  - Bioaccumulation of non-, mono-, and di-ortho-substituted chlorobiphenyls (CBs)
      was investigated in four species of mustelids (weasel, stoat, polecat, and otter)
      and their preys, from a restricted area in the northern part of The Netherlands.
      Diets of these mustelids ranged from terrestrial (weasel, stoat, and polecat) to
      aquatic (otter). Diet-specific biomagnification factors (BMFs), CB in diet
      relative to CB in mustelids, were calculated for the sum of 28 congeners
      (SigmaCB), for the sum of the toxic equivalent concentration (SigmaTEQ) and on an
      individual congener basis. Biotransformation was studied in relation to
      structural CB properties (vicinal H-atom substitution). In addition, the
      methylsulphonyl CB-metabolites were determined. The concentration of SigmaCB on
      lipid weight basis increased in the order weasel < stoat < polecat < otter. On
      the basis of SigmaTEQ, the order changed to weasel < polecat < stoat < otter.
      Most of the differences in BMFs between the CBs could be explained by the vicinal
      H-atom structure-activity rules. For all mustelids, the lowest BMFs were found
      for congeners with vicinal H-atoms in the meta, para position. Indications were
      found that all mustelid species can metabolize these congeners. For some of the
      CBs, their methylsulphonyl-CB metabolites were determined and found to be present
      in concentrations up to 350-fold higher than those of the parent compounds. In
      addition, the non-ortho CBs 126 and 169 are selectively retained in the liver of
      weasel, stoat, and otter. These CBs had the highest BMFs of all congeners.
      However, rather surprisingly, in polecat the highest BMFs were found for di-ortho
      substituted CBs. This animal was able to metabolize all congeners with vicinal H
      atoms in the ortho and meta position (non- and mono-ortho CBs). The information
      concerning the differences in bioaccumulation of CBs for closely related mustelid
      species increased the understanding of reported differences in PCB toxicity
      between mink and ferrets, and suggest that weasel, stoat, and otter are at least
      as sensitive to CBs as are mink, while polecats are less sensitive. As otter is
      exposed to much higher concentrations of CBs trough their diet than weasel and
      stoat, the toxic threat of CBs will be the greatest for this animal.

PMID- 9776785
TI  - Species and organ dependence of PCB contamination in fish, foxes, roe deer, and
      humans.
AB  - According to previous experimental results, PCBs are deposited in muscle fat in
      animals and in humans, although they also reach the brain, the liver, and the
      lungs. The aim of the present study was to determine the concentrations of the so
      called "indicator PCBs" (PCB nos. 28, 52, 101, 138, 153, 180), as described by
      the German ordinance for maximum concentrations of contaminants in foodstuffs, in
      muscle tissue, liver, and brain of four different species: fish, fox, roe deer,
      and humans, all exposed to PCBs directly in their environment. Potential target
      organs for the accumulation of these congeners were also to be identified.
      Furthermore, the organs or tissues were to be identified in which PCBs are
      accumulated, and unusual patterns of accumulation or breakdown of particular
      PCBs, for example the "dioxin-like PCBs" (coplanar PCBs) determined. For humans,
      the lungs were also included in these studies. Statistical comparison of PCB
      concentrations in samples from wild animals and humans showed that in spite of
      its relatively high fat concentration, brain tissue in all of the species
      examined (with the exception of fish) appeared to be better protected against
      accumulation of PCB than liver or muscle tissue. This protection may be the
      result of the blood-brain barrier, as witnessed by the relatively uniform
      concentration of PCBs throughout the various organs of fish, since the blood
      brain barrier of fish is considerably less efficient than that of mammals. No
      peculiarities were found in regard to distribution of the coplanar PCBs over the
      other congeners in this study. This applies to the brain and other organs or
      tissues of the four species that were examined. Accumulations of PCBs and
      coplanar PCBs in the liver were only found in fox and roe deer. In contrast,
      humans were found to have accumulations of the high-chlorinated biphenyls studied
      here as well as PCB no. 118 in muscle tissue fat and not in the liver.
      Unexpectedly, low-chlorinated biphenyls were found to accumulate in the human
      lung. The results of this study show that the lung represents a target organ for
      the accumulation of potentially metabolically activated low-chlorinated
      biphenyls, indicating that the possible biological effects of PCBs on the lungs
      will need to receive more attention in the future.

PMID- 9776786
TI  - Hexachlorocyclohexane and its isomers: regional brain levels in the rat after
      dermal exposure.
AB  - In the present study the distribution of hexachlorocyclohexane (HCH) and its
      isomers in the brain of rats given dermal exposure of this pesticide have been
      investigated using a gas liquid chromatographic technique. The male Druckery rats
      were given dermal exposure of HCH 50 or 100 mg/kg body weight/day in 0.2 ml
      acetone for the period of 60 or 120 days. The results reveal that an appreciable
      quantity of HCH and its isomers alpha, beta, gamma, and delta accumulate in a
      dose- and time-dependent manner in different regions of the brain, which may
      adversely affect the specific physiological function of these brain regions.

PMID- 9776787
TI  - Bioavailability of PCBs to male laboratory rats maintained on litters of
      contaminated soils: PCB burden and induction of alkoxyresorufin O-dealkylase
      activities in liver and lung.
AB  - Male rats from the Sprague-Dawley laboratory strain were maintained in the
      laboratory during 3 days and 1 night on litters containing a reference soil and
      different amounts of a soil, mainly polluted by PCBs (207 ppm expressed in
      Aroclor(R) 1254; SIII soil). Two categories of biomarkers of exposure were
      measured in both liver and lung of these rats: PCB burdens and activities of
      microsomal liver and lung cytochrome P450-dependent mono-oxygenases, namely
      ethoxy-, pentoxy-, and benzoxy-resorufin O-dealkylase activities (EROD, PROD, and
      BROD, respectively). PCB burdens in liver and lung of rats exposed to SIII soil
      were 1,845 and 241 ppb, respectively (expressed in Aroclor(R) 1254 equivalents).
      EROD, PROD, and BROD were significantly induced in the liver of rats exposed to
      SIII soil, while only EROD activity was induced in the lung. Induction of hepatic
      EROD activity was approximately 3- to 5.4-fold; pulmonary EROD activity was
      induced by 9- to 12-fold. In the lung, PROD and BROD activities were inhibited.
      When rats were exposed to SIII soil diluted with various amounts of standard ISO
      soil, a nearly linear dose-response relationship was found between the level of
      PCBs in the litter and EROD activity in both liver and lung. A nonlinear dose
      response relationship exists with hepatic BROD activity; no dose-response
      relationship was observed with hepatic PROD and pulmonary PROD and BROD
      activities. EROD activity measurement in both liver and lung of rats maintained
      on a litter of PCB polluted soil was used to assess the bioavailability to
      mammals of PCBs.

PMID- 9776788
TI  - Technical hexachlorocyclohexane use trends in China and their impact on the
      environment.
AB  - Trends in production of technical HCH (BHC: 1,2,3,4,5, 6-hexachlorocyclohexane)
      in China have been surveyed from 1952 to 1983, when the Chinese government banned
      the use of this pesticide. While the total 4.46 million metric tons produced
      during this period make China by far the biggest producer and user of technical
      HCH, Japan consumed the largest accumulated average amount of this insecticide
      over arable land (84 t/kha for Japan versus 44 t/kha for China). The relationship
      between technical HCH production/usage trends and their impact on the environment
      has been studied. The similarity between total HCH isomer concentrations in
      Chinese environmental compartments in the beginning of 1980s and those in
      Japanese in the beginning of 1970s indicates the linkage between the average
      accumulated usage of technical HCH and the magnitude of contamination in the
      environment by this organochlorine insecticide. According to data from a national
      monitoring program on food contamination by organochlorine pesticides, residues
      of total HCH in foodstuffs in China decreased by about five times in rice, 127
      times in fish, 32 times in poultry eggs, and 32 times in meat between 1978 and
      1992.

PMID- 9776789
TI  - Efficiency of safety measures applied to a manual knapsack sprayer for paraquat
      application to maize (Zea mays L.).
AB  - The objectives of the present study were to evaluate the safety of mixer/loaders
      and applicators of paraquat to maize crop by knapsack sprayers and to determine
      the efficacy of safety measures applied to the sprayers. Potential dermal
      exposure (PDE) was evaluated in 22 worker body parts. The Cu2+ cation of a copper
      based fungicide was used as tracer in the spray solution. Sanitary pads and
      cotton gloves were used to collect the pesticide solution on the sampled body
      parts. It was observed that paraquat application in front of the applicator's
      body (0.5 and 1.0 m lance) is unsafe because PDE was 1,979.8 ml/day (for 0.5 m
      lance) and 1,290.4 ml/day (for 1.0 m lance) and needs 50-80% and 37-69% control
      of PDE respectively. Control can be achieved by the use of protective garment on
      the legs and feet only, which received 92-93% of the PDE. Switching the spray
      nozzle to the back of the operator reduced the PDE by 98% and was sufficient to
      make working conditions safe, while maintaining the efficiency of application and
      making the work lighter and more comfortable. Mixer/loaders received 86% of the
      PDE to the hands and the work condition was safe (MOS > 1), however impermeable
      gloves could be used as a further safety measure.

PMID- 9776790
TI  - Twenty-five years of surveillance for contaminants in human breast milk.
AB  - To monitor the exposure of Canadian populations, Health Canada has carried out
      six major surveys of breast milk contaminants, beginning in 1967. In these
      national surveys, breast milk was collected from nursing mothers at various times
      in their nursing period, and the concentrations of chlorinated hydrocarbons were
      measured. There was a downward trend from 1967 to 1992, in the concentrations of
      organochlorine (OC) pesticides and polychorinated biphenyl hydrocarbons (PCBs).
      This regression was observed for samples across Canada, except for a sharp
      isolated increase in 1982 for the Quebec Province. As the disappearance curves of
      the chemicals surveyed follow the same pattern for both Ontario and Canada, a
      similar decline could be expected of OC concentrations in human breast milk in
      the Great Lakes Basin.

PMID- 9776791
TI  - Estimation of target hazard quotients and potential health risks for metals by
      consumption of seafood in Taiwan.
AB  - The purpose of this paper is to describe the impact of metal pollution on the
      main seafood and assess the potential health risk from consuming the contaminated
      seafood in Taiwan. The results of geometric mean (GM) metal concentrations in
      various seafood showed that the copper, zinc, and arsenic concentrations in
      oysters were significantly (p < 0.001) higher than those in the other seafood by
      about 1,057, 74.3, and 56.2 times, respectively. The green color found in the
      oysters was due to high GM copper and zinc concentrations of 909 (ranging from
      113-2,805) and 1,293 (ranging from 303-3,593) microg/g dry wt, respectively. In
      addition, using a maximum consumption rate of 139 g/day of oysters for
      individuals, calculations yield target hazard quotients (daily intake/reference
      dose) of below 1 for cadmium and mercury and high values of 1.61, 9. 33, and 1.77
      for inorganic arsenic, copper, and zinc in adults, respectively. The various
      lifetime cancer risks for inorganic arsenic (maximum exposed individuals risk
      ranging from 9.93 x 10(-6) to 3.11 x 10(-4)) might be caused by consuming
      different seafood in Taiwan. The highest risk estimate for inorganic arsenic was
      5.10 x 10(-4) for consumption of oysters by Machu Islands residents. The long
      term exposure of metals through consumption of oysters, especially for some high
      risk groups, could be dangerous. Taking inorganic arsenic for example, a 10(-6)
      upper limit on lifetime risk as the health protection standard would require
      maximum oyster residue levels of approximately 0.0076-0.056 microg/g wet wt, for
      consumption rates of 139-18.6 g/d. In the light of known risks to public health,
      the government should issue an immediate warning to the public to refrain from
      eating all seafood harvested from the Taiwan coastal areas, especially the
      Hsiangshan area and the Machu Islands.

PMID- 9776792
TI  - International endstage renal disease (ESRD) outcome comparisons.

PMID- 9776793
TI  - Effects of low-protein diet on carbohydrate metabolism and energy expenditure.
AB  - Low-protein diets (LPD), which are prescribed for uremic patients to slow the
      progression of chronic renal failure, theoretically may exacerbate disorders of
      carbohydrate metabolism that are frequently observed in these patients because
      increased carbohydrate rations are required to maintain a sufficient caloric
      intake. No such exacerbation actually occurs. Glucose tolerance has been shown to
      improve after 3 months of a diet affording .3 g protein/kg body weight
      supplemented with essential amino acids and ketoanalogs with carbohydrates
      accounting for 67% of the total energy intake. Hyperinsulinemic euglycemic clamp
      studies show that this amelioration is linked with an increase in insulin
      sensitivity, which is also observed in uremic diabetic patients on this diet. The
      improvement in glucose tolerance involves the insulin sensitivity of endogenous
      glucose production, glucose oxidative disposal, and its nonoxidative disposal.
      Besides these effects, LPD increases the metabolic clearance rate of insulin and
      causes blood insulin levels to decrease. LPD's low acid load and phosphorus
      content, the reduced synthesis of uremic toxins derived from alimentary protein,
      or both may explain these effects, which are indirectly protective against
      atherosclerosis. However, the significant increase in resting energy production
      after 3 months on LPD justifies strict monitoring of nutritional status and
      caloric intake.

PMID- 9776794
TI  - Barriers to adequate protein nutrition among hemodialysis patients.
AB  - OBJECTIVE: Determine the relative importance of potential medical, behavioral,
      and socioeconomic barriers to adequate protein nutrition among hemodialysis
      patients. DESIGN: Cross-sectional study. SETTING: All 22 chronic hemodialysis
      units in northeast Ohio. PATIENTS: 298 randomly selected chronic hemodialysis
      patients. INTERVENTION: We interviewed and abstracted the chart of each patient
      to assess protein nutritional status (albumin and protein catabolic rate),
      potential medical barriers (poor appetite, inadequate dialysis, bioincompatible
      dialysis membrane, difficulty chewing, and comorbid conditions), potential
      behavioral barriers (knowledge of protein containing foods and dietary
      noncompliance), and potential socioeconomic barriers (expense of protein
      containing foods and needing help shopping and cooking). MAIN OUTCOME MEASURE: We
      used logistic regression to examine the relationship between protein nutritional
      status and potential barriers. RESULTS: Albumin levels of <35 g/L were
      independently associated with Kt/V of <1.2 (odds ratio, 2.4), having more than
      three comorbid conditions (odds ratio, 4.0), inability to name any protein
      containing foods (odds ratio, 2. 3), and needing help shopping and cooking (odds
      ratio, 2.6). Normalized protein catabolic rate of <1.0 g/kg/d was independently
      associated with poor appetite (odds ratio, 3.3), Kt/V of <1.2 (odds ratio, 3.1),
      and dietary compliance as indicated by low interdialytic fluid gain (odds ratio,
      2.2). CONCLUSION: Three medical factors (poor appetite, inadequate dialysis, and
      comorbid conditions), two behavioral factors (lack of knowledge of protein
      containing foods and low interdialytic fluid gain), and one socioeconomic factor
      (needing help shopping and cooking) are independently associated with inadequate
      protein nutrition among hemodialysis patients. Further work is needed to develop
      interventions to overcome these barriers and to determine the effect of such
      interventions on protein nutrition and patient mortality and morbidity.

PMID- 9776796
TI  - Validation of 24-hour dietary recall: a study in hemodialysis patients.
AB  - The 24-hour dietary recall method is frequently used for dietary assessment.
      However, it is subject to errors by both respondent and observer bias and is
      largely influenced by the motivation and recall ability of the respondent. The
      weighment method is regarded as the gold standard for estimating nutrient intake.
      This study was undertaken to assess the validity of dietary recall in a group of
      seven maintenance hemodialysis patients, who also had corresponding weighed food
      records. Actual food consumed and residue were weighed separately. A dietary
      recall was taken on the next day. Subjects were not allowed to take any food or
      beverage other than that served during the study period. A good agreement was
      obtained between dietary recall and the weighed food record (the difference was
      within 10% of the results of weighment), although there was a consistent
      underestimate by dietary recall. The results also suggested a training effect
      since improved recall was noted during the later weeks of the study, although
      this difference was not statistically significant. Therefore, dietary recall as a
      method of dietary assessment may be of special value in chronic hemodialysis
      patients in India, who are usually a motivated and informed group.

PMID- 9776795
TI  - Renal dietitians' perspective: identification, prevalence, and intervention for
      malnutrition in dialysis patients in Texas.
AB  - OBJECTIVE: Determine the prevalence of malnutrition per facility standards;
      examine interventions used to treat malnutrition; and share experiences,
      concerns, and solutions to problems in the management of malnutrition in dialysis
      patients in Texas. DESIGN: Structured survey questionnaires. SETTING: 196
      outpatient hemodialysis (HD) and 86 peritoneal dialysis (PD) programs in End
      Stage Renal Disease (ESRD) Network of Texas, Inc. PARTICIPANTS: Renal dietitians
      who worked in Texas dialysis facilities that treated chronic, outpatient adult,
      and pediatric ESRD patients on HD or PD. MEASIRES: Criteria used to identify
      malnourished patients, prevalence of malnutrition in dialysis recipients,
      prevalence and types of interventions used to manage malnourished patients, and
      participation in quality management activities among renal dietitians. RESULTS:
      For facilities that treated both HD and PD patients in 1996: (1) a significantly
      greater proportion of PD patients were identified as malnourished than HD
      patients; (2) facilities that had a high percentage of malnourished HD patients
      also had a high percentage of malnourished PD patients; (3) a significantly
      greater proportion of PD patients received commercial nutrition supplements than
      HD patients; and (4) use of tube feedings, intradialytic parenteral nutrition,
      intraperitoneal parenteral nutrition, and total parenteral nutrition among HD and
      PD patients decreased significantly from the past to the current survey year.
      Renal dietitians shared their experiences, concerns and solutions to problems in
      the management of malnutrition in this population. CONCLUSION: Results indicate a
      need to improve the nutritional status of malnourished dialysis patients, to
      increase consideration of tube feedings as viable nutrient delivery routes, and
      to maximize involvement of renal dietitians in the quality management process.
      With the cooperative effort of staff, care givers, patients, and family, early
      identification and appropriate interventions may improve the nutritional status
      and quality of life of dialysis patients. This is a US government work. There are
      no restrictions on its use.

PMID- 9776798
TI  - Energy supplementation in chronic hemodialysis patients with moderate and severe
      malnutrition.
AB  - OBJECTIVE: Prospectively evaluate the effect on the nutritional status of a
      glucose polymer as energy supplementation alone in chronic hemodialysis patients
      with moderate and severe malnutrition. MATERIAL AND METHODS: The nutritional
      status of 55 hemodialysis patients was assessed by using a score that included
      Iron binding capacity, albumin, cholesterol, body mass index, mid brachial
      circumference, arm muscle area, triceps skinfold, and clinical impression. Twenty
      two of 27 patients (14 men and 8 women, mean age 43 +/- 15 years, time on
      dialysis 65 +/- 49 months) were classified as moderately or severely malnourished
      and were supplemented for 6 months with 100 g of glucose polymers per day
      (equivalent to 380 kcal or 1590 kJ) added to the usual food intake. The patients
      were reevaluated at 3 and 6 months. RESULTS: Only body weight, body mass index,
      triceps skinfold, and brachial circumference and clinical impression increased
      significantly at the end of the third month (P < .05) in the 22 patients. These
      results were confirmed at 6 months in 18 patients that completed the study. Mean
      body weight increase was 2.4 kg (range, .2 to 6.3 kg). The nutritional status,
      evaluated through the score, improved in only 4 patients at the end of the study.
      Few gastrointestinal side effects were observed. Triglycerides increased from 136
      +/- 40 mg/dL to 235 +/- 120 mg/dL. Follow-up of the patients showed that fat mass
      (assessed by anthropometry) was maintained for 6 months after supplementation was
      discontinued. CONCLUSION: Energy supplementation alone in patients with moderate
      and severe malnutrition on chronic hemodialysis resulted in an increase in body
      weight, owing to an increase in body fat, but the nutritional status did not
      improve.

PMID- 9776797
TI  - The effect of a self-monitoring tool on self-efficacy, health beliefs, and
      adherence in patients receiving hemodialysis.
AB  - OBJECTIVE: Assess the effectiveness of a self-monitoring tool on perceptions of
      self-efficacy, health beliefs, and adherence in patients receiving hemodialysis.
      DESIGN: A monthly intervention using a pretest, posttest design over a 6-month
      period. Both the treatment and control groups were randomly selected and received
      surveys to assess health beliefs, perceptions of self-efficacy for performing
      specific healthful behaviors, and renal diet knowledge at baseline, before
      intervention, and 6 months later. The treatment group also received monthly
      feedback of monthly phosphorus levels and interdialytic weight gains. SETTING: A
      university hospital-based 43-chair ambulatory dialysis center. SUBJECTS: Forty
      patients with end-stage renal disease (25 men and 15 women, age 26 to 78 years),
      on chronic hemodialysis for at least 2 months and with a history of noncompliance
      with phosphorus and/or fluid restrictions for 1 or more months. MAIN OUTCOME
      MEASURES: Self-efficacy, health beliefs, knowledge, biochemical, and demographic
      variables were analyzed. Analysis of variance tests of repeated measures were
      used to examine relationships between adherence with phosphorus and fluid
      restrictions to health beliefs and perceptions of self-efficacy after training in
      self-monitoring. RESULTS: Overall, there were no significant improvements in
      adherence with phosphorus and fluid restrictions between the two groups, although
      a comparison within the groups revealed the treatment group had a statistically
      significant decrease in mean phosphorus levels of 7.14 to 6.22 mg/dL (P = .005)
      from baseline to month 3. However, because this value was not maintained, it was
      not statistically significant. No significant differences existed between the two
      groups for health beliefs and perceptions of self-efficacy. Knowledge scores in
      the treatment group, however, improved significantly as compared to the control
      group (P = .008) and was a significant increase from baseline (P = . 002). In the
      control group, all scores fell slightly but this difference was not significant.
      CONCLUSIONS: The benefits of patient self-monitoring and behavioral contracting
      upon adherence in patients on hemodialysis are inconclusive, as serum phosphorus
      and interdialytic weight gains did not differ between the two groups. The
      interventional tools also appeared to have little effect on perceptions of self
      efficacy and health beliefs. Trends of improvement, however, did exist for
      phosphorus within the treatment group and subjects in this group had a
      statistically significant increase in knowledge scores over time. Additional
      research using repeated measures design is needed to explore the effects of
      increased frequency and duration of an intervention on the attainment of patient
      clinical outcome measures.

PMID- 9776800
TI  - Product update 

PMID- 9776799
TI  - Low phosphorus and low potassium food list.

PMID- 9776801
TI  - Abstracts of the 48th annual NKF meeting october 22-25, 1998 philadelphia,
      pennsylvania 

PMID- 9776804
TI  - Subject index 

PMID- 9776802
TI  - Message from the chairperson 

PMID- 9776805
TI  - Interstrain variation in the deoxynucleotide composition of Cryptococcus
      neoformans: nucleotide composition of Cryptococcus neoformans.
AB  - The deoxynucleotide (dNMP) composition of ten strains of C. neoformans was
      analysed by 32P-labelling and two-dimensional thin-layer chromatography. This
      technique is very sensitive for detecting rare deoxynucleotide adducts and
      analogues (minor bases) in DNA. The results indicate considerable variation among
      strains in DNA nucleotide composition.

PMID- 9776806
TI  - Different utilization of neutral lipids by Malassezia furfur and Malassezia
      sympodialis.
AB  - In recent years, the genus Malassezia has been expanded based on molecular data;
      in addition to M. furfur and M. pachydermatis, five new species (M. sympodialis,
      M. globosa, M. obtusa, M. restricta, M. slooffiae) have been described. Apart
      from their lipid dependence, little is known about the metabolism and nutritional
      requirements of these new species. Defined inocula of Malassezia reference
      strains were cultured on selective agar for pathogenic fungi which was overlaid
      with olive oil. Samples of the olive oil overlay were taken at regular intervals
      and the lipid fractions were analysed by high performance thin layer
      chromatography. Depending on the time of incubation and the number of cells, M.
      sympodialis and the other recently described species produced a significant
      increase in free fatty acids. In addition, a band of an apolar substance was
      identified as a mixture of fatty acid ethyl esters. While showing growth, strains
      of M. furfur produced only small amounts of ethyl esters and free fatty acids.
      The growth kinetics of M. furfur and M. sympodialis were also different: for M.
      sympodialis, a clear lag phase was observed, possibly indicating the necessity of
      extracellular hydrolysis of the triglycerides. The significance of the synthesis
      of ethyl esters could not be clarified. For routine differentiation, this
      metabolic difference is only of limited usefulness because slight contamination
      of M. furfur strains with other lipophilic Malassezia species may lead to
      misinterpretation due to the high metabolic activity. These metabolic differences
      might be important in the pathogenesis of Malassezia infections.

PMID- 9776807
TI  - Colonization of living skin equivalents by Malassezia furfur.
AB  - Initial colonization events and yeast-hyphal transformation by Malassezia furfur
      were observed using living skin equivalent (LSE) models for growth. Yeast cells
      were inoculated onto the LSEs which were incubated in CO2-independent media at 37
      degreesC for variable lengths of time. Assessment of fungal growth and invasion
      was by light- and scanning electron microscopy (SEM). Viability counts of M.
      furfur were determined by a method of washing and serial dilution. Yeast cells
      had retained their viability and increased in number approximately twofold over a
      4-day period of incubation. Yeast-to-hyphal transition was not achieved in this
      model. Random destruction of the uppermost layers of the stratum corneum was
      observed in the presence of M. furfur. LSEs therefore appear to be a promising
      model for mechanisms of growth of cutaneous organisms.

PMID- 9776808
TI  - Characteristic infectivity of Sporothrix schenckii to mice depending on routes of
      infection and inherent fungal pathogenicity.
AB  - Isolates of Sporothrix schenckii were examined for their infectivity in BALB/c
      mice. The mice were injected with yeast forms of S. schenckii isolates differing
      in clinical source (human cutaneous lesions and pulmonary lesions), and fungal
      growth was determined at intervals in the footpad and visceral organs. After
      subcutaneous injection of approximately 10 colony forming units (cfu) of S.
      schenckii into the footpad, locally restricted fungal infection developed
      gradually. At the peak of the infection (3-4 weeks post-inoculation), viable
      fungal counts reached 102-106 cfu/footpad. Dissemination to other tissues and
      visceral organs was not observed. After intravenous or intraperitoneal injection
      of 106 cfu of yeast forms, three of four isolates from cutaneous sporotrichosis
      were unable to establish infection and were eliminated from blood and visceral
      organs. The development of systemic infection was observed only with S. schenckii
      isolates obtained from the human lung lesion. Thus, inherent properties of each
      clinical isolate and routes of infection were shown to be critical for the
      establishment of systemic infection in spite of the remarkably strong infectivity
      of S. schenckii to the cutaneous tissue.

PMID- 9776809
TI  - Analysis of fluconazole effect on Candida albicans viability during extended
      incubations.
AB  - Fluconazole is an azole agent with primarily fungistatic activity in standard in
      vitro susceptibility tests. However, recent work has demonstrated that this drug
      can reduce Candida albicans viability during prolonged incubations under non
      growing conditions. The present study was undertaken to examine more closely some
      of the parameters of this killing activity. Fungicidal effects of 1.0 microg ml-1
      of fluconazole were found during 7-14-day exposures in each of two media that
      prevented proliferation, distilled water and metal-depleted RPMI 1640 tissue
      culture medium. Fluconazole appeared to be stable after being incubated at 37
      degreesC for either 7 or 14 days. Strains of C. albicans resistant to fluconazole
      in standard short-term growth-inhibition assays were also found to be resistant
      to fluconazole's effect on viability in prolonged culture, suggesting similar
      mechanisms of action for these effects. C. albicans yeast cells pre-incubated for
      7 days in distilled water were not more sensitive to the drug in short-term
      susceptibility assays. Although all proliferation of the organisms in distilled
      water cultures appeared to cease after 3 days, fluconazole added at 7 days still
      reduced C. albicans viability. Therefore, the drug appeared to kill the non
      proliferating organisms directly rather than preventing growth and thereby the
      emergence of younger organisms that would live longer. Transmission electron
      microscopy demonstrated damage to the cell wall-cell membrane complex and
      interior contents of yeast cells incubated in distilled water alone; fluconazole
      appeared to increase the percentages of cells so affected. In summary, extended
      incubation susceptibility tests demonstrated that fluconazole has direct
      fungicidal activity of non-proliferating C. albicans yeast cells. These results
      may be relevant to the manner in which this drug promotes clearance of chronic
      fungal infections.

PMID- 9776810
TI  - Isolation of a Paracoccidioides brasiliensis strain from the soil of a coffee
      plantation in Ibia, State of Minas Gerais, Brazil.
AB  - Paracoccidioides brasiliensis has rarely been isolated from its habitat in rural
      areas. In order to investigate the hypothesis that human infection with this
      fungus is linked to coffee plantations (Coffea arabica), material was collected
      monthly over a period of 1 year from farms in the town of Ibia, State of Minas
      Gerais, Brazil. A total of 760 samples of soil, coffee leaves and fruits was
      cultured and inoculated into mice. A fungus isolated from the liver of a mouse
      inoculated with soil showed temperature-dependent dimorphism and in vitro
      mycelium and yeast phases characteristic of P. brasiliensis. Yeast cells of this
      fungus caused disseminated infection after intraperitoneal inoculation in Wistar
      rats from which the fungus was re-isolated. An antigen reacting with sera from
      patients with paracoccidioidomycosis was obtained from this P. brasiliensis
      strain; antigenic identity with strain 339 and with four other P. brasiliensis
      strains was detected by gel immunodiffusion. However, when the exo-antigen was
      submitted to SDS-PAGE, we observed low gp43 expression in this new strain, which
      we called Ibia. The isolation of P. brasiliensis from the soil at a coffee
      plantation suggests that this is one of its habitats and supports the hypothesis
      of acquisition of paracoccidioidomycosis during agricultural activity in these
      areas.

PMID- 9776811
TI  - Auricular chromoblastomycosis caused by Rhinocladiella aquaspersa.
AB  - An unusual case of chromoblastomycosis localized in the ear and caused by R.
      aquaspersa is presented. The patient was a 60-year-old male urban resident, who
      had had the disease for 5 years. The lesion was darkly pigmented, infiltrative
      and crusty. Sclerotic cells were seen on direct examinations and the fungus was
      recovered in culture and identified on the basis of the characteristic
      sporulation. Itraconazole therapy at a dose of 200 mg day-1 for 7 months produced
      complete healing.

PMID- 9776812
TI  - Simultaneous infection with Blastomyces dermatitidis and Cryptococcus neoformans.
AB  - In this report, we present two cases of simultaneous infection with Blastomyces
      dermatitidis and Cryptococcus neoformans. In both cases, fungi were isolated from
      the lungs. The clinical manifestations were not suggestive of infection with two
      fungi. One patient was receiving immunosuppressive therapy and another was
      otherwise immunocompetent. A review of the literature failed to uncover any
      reports of co-infection with these two fungal pathogens. We discuss possible
      mechanisms for the isolation of both pathogens.

PMID- 9776813
TI  - Invasive hyphomycotic rhinitis in a cat due to Metarhizium anisopliae.
AB  - Invasive mycotic rhinitis was diagnosed in a cat with a 4-month history of
      stertor, nasal discharge and subcutaneous swelling of the nasal bridge. Histology
      demonstrated fungal hyphae in representative biopsies of the nasal cavity and
      subcutaneous mass. Mycological culture demonstrated a pure growth of Metarhizium
      anisopliae var. anisopliae. The infection was treated with orally administered
      itraconazole. This is the first well documented case of infection by M.
      anisopliae in a mammalian host.

PMID- 9776814
TI  - Increased incidence of Trichophyton tonsurans tinea capitis in Ontario, Canada
      between 1985 and 1996.
AB  - In Canada, since the 1990s, Trichophyton tonsurans has emerged as the main cause
      of tinea capitis. Prior to this the more common agents were T. verrucosum,
      Microsporum canis and M. audouinii. Over the past few years the incidence of T.
      tonsurans has increased such that in 1985 and 1996 the cases of mycologically
      confirmed tinea capitis due to T. tonsurans were 9% and 76%, respectively. The
      epidemic of T. tonsurans has reduced the role of Wood's lamp in diagnosis of
      tinea capitis. The age distribution of tinea capitis due to T. tonsurans closely
      matches that of mycologically confirmed tinea capitis, being most common in
      children under 14 years of age. There is no significant sex difference in
      children who develop T. tonsurans tinea capitis; however, subjects are
      significantly more likely to live in urban than rural areas. This should provide
      guidance regarding where to concentrate health resources and deliver
      patient/parent education to combat this epidemic of tinea capitis.

PMID- 9776816
TI  - Does hydrocortisone modify the in vitro susceptibility of Aspergillus fumigatus
      to itraconazole and amphotericin B?
AB  - To analyse if hydrocortisone could modify the in vitro susceptibility of
      Aspergillus fumigatus to antifungal drugs, we developed a procedure to test the
      susceptibility of an A. fumigatus strain to amphotericin B and itraconazole,
      grown in the presence and in the absence of hydrocortisone. Conidia were
      germinated in the presence or the absence of hydrocortisone in Czapek medium
      without antifungal drug. A dilution of these cultures (5x10(3) conidia ml(-1))
      was spread onto Czapek-agarose plates containing both antifungal drug and
      hydrocortisone. The cfu per plate were enumerated and compared. A therapeutic
      concentration of hydrocortisone induced a significant increase in the
      susceptibility to itraconazole. Conversely, the susceptibility to amphotericin B
      was not significantly modified when this antifungal drug was associated with
      hydrocortisone.

PMID- 9776815
TI  - PCR-based identification of clinically relevant Pseudallescheria/Scedosporium
      strains.
AB  - Pseudallescheria boydii (anamorph: Scedosporium apiospermum) and S. prolificans
      can cause severe infections in both the immunocompromized host and accidentally
      injured people. A species-specific polymerase chain reaction (PCR) enabling
      detection and discrimination of these fungi has not been available to date. In
      view of the difficult treatment especially of S. prolificans infections, a PCR
      based detection system has been developed. Based on results of partial sequencing
      of ribosomal DNA, Scedosporium DNA could be amplified, either at the genus or at
      the species level. Hybridization probes for the identification of the PCR
      products were established.

PMID- 9776818
TI  - UV irradiation induced high frequency of colonial variants with altered
      morphology in Sporothrix schenckii.
AB  - Ultraviolet light (UV) exposure of Sporothrix schenckii strains resulted in a
      high frequency of morphological variants that ranged from 10(-3) to 10(-1)
      depending on the strain and dose of UV. Based on their morphological differences,
      these variants were classified into five different groups. One common feature
      among them was that they were smaller in size compared to the wild type. Two
      morphological phenotypes (II and IV) were fuzzy, like the wild-type colony, and
      only the colony size was altered. Phenotypes I, III and V had different shapes;
      they lost the fuzzy appearance and the individual hyphae in the colony were of
      aberrant shape. Stable and non-stable morphological variants were found in the
      population; reversion of the mutant phenotype was always to the wild-type
      phenotype. Unlike Candida albicans, phenotypic switching was not found in
      individual colonial phenotypes.

PMID- 9776817
TI  - Lysis of Paracoccidioides brasiliensis by Zygosporium geminatum.
AB  - Zygosporium geminatum, isolated as a contaminant in a culture of the mycelial
      phase of Paracoccidioides brasiliensis, was lethal to the latter organism. Its
      lytic action was due to exocellular alpha-1,3- and beta-1,3-glucanases which
      degraded the P. brasiliensis cell wall. The alpha-1,3-glucanase was more active
      at 30 degrees C and the beta-1,3-glucanase at 23 degrees C, each having pH 6.0 as
      its optimum.

PMID- 9776819
TI  - Bovine mammary protothecosis due to Prototheca zopfii.
AB  - Mastitis due to Prototheca zopfii was diagnosed in three of 28 cows in a dairy
      herd. As two cows continued to shed algae after 45 days they were slaughtered and
      organs were examined by cultivation, histology, immunohistochemistry and electron
      microscopy. Algae were restricted to the mammary glands and regional lymph nodes
      in which a granulomatous inflammation was seen. Algae were predominantly seen in
      macrophages but neutrophils also contained organisms. In macrophages both
      sporangiospores and sporangia were found, suggesting that intracellular
      proliferation may be responsible for the failure to overcome the infection. Serum
      samples from all cows were assayed for antibodies against P. zopfii in an enzyme
      linked immunosorbent assay (ELISA). Although the highest titre was found in an
      infected cow the difference between the mean values of the titre in infected and
      non-infected cows was not significant.

PMID- 9776820
TI  - The effects of Malassezia on pro-inflammatory cytokine production by human
      peripheral blood mononuclear cells in vitro.
AB  - Malassezia spp., the causative agents of pityriasis versicolor, are members of
      the normal human cutaneous microflora. Utilizing a combination of both enzyme
      linked immunosorbent assay (ELISA) and bioassay, we have investigated the ability
      of both formalin-preserved and viable Malassezia (serovars A, B and C) to
      modulate pro-inflammatory cytokine (IL-6, IL-1beta and TNF-alpha) release by
      human peripheral blood mononuclear cells (PBMNC) in vitro, over a 48-h co
      incubation period. The results demonstrated that formalin-preserved Malassezia
      (serovars A, B and C) at mid-exponential phase were generally able to induce a
      pro-inflammatory cytokine response at a yeast cell to PBMNC ratio of 1:1. In
      addition, the results consistently demonstrated that at a yeast cell to PBMNC
      ratio of 20:1, formalin-preserved Malassezia, irrespective of serovar, growth
      phase or PBMNC donor, were capable of significantly (P<0.05) decreasing the
      release of both immunochemical IL-6 and IL-1beta plus bioactive IL-1beta and TNF
      alpha below that of unstimulated culture medium control values. This was apparent
      following 24- and 48-h co-incubation times, where maximal cytokine production was
      detected after 24 h. Similar results were obtained for the effect of viable
      Malassezia on pro-inflammatory cytokine release by PBMNC. Our results suggest
      that a possible inhibitory component, present perhaps within the cell wall of
      Malassezia, was responsible for this depressive effect on pro-inflammatory
      cytokine production.

PMID- 9776822
TI  - Fatal aortic Myceliophthora thermophila infection in a patient affected by cystic
      medial necrosis.
AB  - A 22-year-old Italian woman developed fungal aortitis after cardiac surgery for
      aortic insufficiency. She experienced two episodes of septic embolization and
      subsequently underwent replacement of the aortic root and initial ascending aorta
      by a homograft. The lumina of the ascending aorta, aortic arch and the origin of
      the innominate artery were completely filled with vegetation. From the involved
      tissue the phaeoid thermophilic hyphomycete Myceliophthora thermophila (Apinis)
      van Oorschot was isolated in pure culture. This is the second report of isolation
      of this fungus from humans and the first isolation of a human pathogenic strain
      of M. thermophila causing fatal vasculitis in a patient affected by cystic medial
      necrosis. A detailed morphological description of the isolate is also provided.

PMID- 9776821
TI  - Systemic aspergillosis caused by an aflatoxin-producing strain of Aspergillus
      flavus.
AB  - The first case of human systemic infection by an Aspergillus flavus isolate
      demonstrated to produce aflatoxins in vitro and in vivo is described. The
      patient, a 41-year-old man with acute myelogenous leukaemia, developed a
      complication of suspected pulmonary Aspergillus infection during remission
      induction therapy. Antifungal chemotherapy brought about a considerable degree of
      improvement, but remission of the underlying disease was not attained. Bone
      marrow transplantation was also not effective. The patient showed recovery from
      neutropenia but died despite aggressive antifungal chemotherapy. The autopsy
      revealed lesions in the lungs, myocardium, kidneys, brain, thyroid gland and skin
      due to a suspected Aspergillus sp. A fungus isolated from the right lung and the
      skin lesions was identified as A. flavus. Aflatoxins B1, B2 and M1 were detected
      in culture filtrates of the isolated A. flavus, and in an extract of lung
      lesions. These aflatoxins are considered to have played an important role in
      damaging the immune system of the patient through their toxic effects.

PMID- 9776823
TI  - Cryptococcus neoformans var. gattii--evidence for a natural habitat related to
      decaying wood in a pottery tree hollow.
AB  - To study hollows of living trees as the natural habitat of Cryptococcus
      neoformans in an endemic area of cryptococcosis in the northeastern Brazilian
      region, samples of decaying wood were collected inside the hollows, plated on
      niger seed agar and inoculated into mice and hamsters. Identification of C.
      neoformans was based on morphological and physiological tests. Canavanine-glycine
      bromothymol medium was used to screen the varieties and Crypto Check Iatron Kit
      to serotype the isolates. For a period of 29 months C. neoformans var. gattii
      serotype B was isolated repeatedly from the hollow of a pottery tree (Moquilea
      tomentosa), pointing to the natural occurrence of C. neoformans var. gatti in
      decaying wood forming hollows in living trees. Evidence for a natural habitat of
      the variety gattii other than that related to Eucalyptus camaldulensis are
      discussed.

PMID- 9776824
TI  - Promotion of chlamydoconidium formation in Candida albicans by corn meal broth
      incubation.
AB  - Chlamydoconidium formation can be used as a tool for the identification of
      Candida albicans. While chlamydoconidia are known to be inducible on corn meal
      agar, this report demonstrates that testing in liquid media supplemented with
      milk or serum enhances chlamydoconidium formation and the formation of complex
      mycelial clusters.

PMID- 9776825
TI  - Polar lipids of Aspergillus fumigatus, A. niger, A. nidulans, A. flavus and A.
      terreus.
AB  - Little is known of the phospholipid composition of Aspergillus species. The aim
      of this study was to determine individual phospholipid analogues in Aspergillus.
      Twenty-nine clinical and environmental isolates from five Aspergillus species
      were analysed. Fast atom bombardment mass spectrometric data were considered in
      two ranges, m/z 190-500 and m/z 500-1000, to facilitate the recognition of major
      fatty acyl groups and phospholipids. Quantitative comparison of major anions in
      both m/z ranges was undertaken. Confirmation of major phospholipid anions from
      eight representative isolates was achieved by tandem mass spectrometry. The major
      phospholipid families were phosphatidic acid (PA), phosphatidylethanolamine (PE),
      phosphatidylinositol (PI), and phosphatidylserine (PS). Anions were detected
      consistent with the presence of specific phospholipid moieties, such as palmitoyl
      linolenoyl phosphatidic acid, palmitoyl-oleoylphosphatidylethenolamine, oleoyl
      linoleoyl-phophatidylserine and palmitoyl-linoleoyl-phosphatidylinositol. It
      appears that there is some commonality of sn1 or sn2 fatty acyl substituents,
      frequently C18:2 at sn1 accompanied by C16:0 at sn2, with differing molecular
      weights being attributable to analogues with differing head groups. Differences
      in certain phospholipids (e.g. minor peak with m/z 933) were detected between A.
      fumigatus, A. nidulans and other species examined which could have diagnostic
      value.

PMID- 9776826
TI  - Antimicrobial activity of AmBisome and non-liposomal amphotericin B following
      uptake of Candida glabrata by murine epidermal Langerhans cells.
AB  - The antifungal efficacy and cellular toxicity of AmBisome(R) and non-liposomal
      amphotericin B were compared in cultured epidermal Langerhans cells infected with
      Candida glabrata. Uptake of the yeast was determined by light and electron
      microscopy, and viability was assessed by plating dilutions of lysates from yeast
      infected Langerhans cells and counting colony forming units. The Candida-infected
      Langerhans cells were incubated for 6, 24 or 48 h with 12.5 micro ml-1 of
      AmBisome or non-liposomal amphotericin B, non-drug-containing liposomes or media.
      Intracellular C. glabrata incubated with media or non-drug-containing liposomes
      showed a 2 log increase in cfu, and microscopic examination revealed budding
      yeast within the Langerhans cells. Both liposomal and non-liposomal amphotericin
      B treatment reduced intracellular growth of C. glabrata by 5 logs over 48 h of
      incubation. A morphometric analysis of cell ultrastructure demonstrated that
      AmBisome-treated Langerhans cells retained their cell architecture, but
      Langerhans cells treated with non-liposomal amphotericin B were characterized by
      the absence of intact organelles, disrupted non-granular cytoplasm and the
      presence of many large vacuoles. In conclusion, AmBisome was significantly less
      toxic for epidermal Langerhans cells than amphotericin B, but demonstrated
      comparable antifungal efficacy. After 48 h of drug exposure, both forms of
      amphotericin B effectively inhibited intracellular growth of C. glabrata, but
      only AmBisome did not damage the Langerhans cells.

PMID- 9776827
TI  - Exophiala dermatitidis and Sarcinomyces phaeomuriformis: ITS1-sequencing and
      nutritional physiology.
AB  - The internal transcribed spacer 1 (ITS1) sequences of the nuclear rRNA gene
      (approximately 200 bp) of 33 strains of the Exophiala dermatitidis complex were
      determined; two similar species were added for comparison. A core group (I),
      including the type strain CBS 207. 35, contained 20 identical strains which had
      previously been found to have introns in their small sub-unit (SSU) rDNA. Eleven
      remaining strains identified as E. dermatitidis (groups II-V) differed from the
      core group in 1-4 nucleotide positions (plus a deletion in one strain); most of
      them lacked introns in their SSU ribosomal genes. The type strain of the
      meristematic species Sarcinomyces phaeomuriformis CBS 131.88 was found to differ
      significantly from E. dermatitidis. One strain had the annellidic morphology of
      E. dermatitidis, but the ITS1 sequence of S. phaeomuriformis. Strain CBS 709.95,
      an E. dermatitidis reported to have a meristematic synanamorph, was found to have
      ITS1 identity to the type strain of E. dermatitidis, although SSU sequences
      established previously suggested a close relationship with S. phaeomuriformis.
      Slight physiological differences were found between E. dermatitidis and S.
      phaeomuriformis. An oligonucleotide probe specific for E. dermatitidis was
      designed, thus able to discriminate this species from closely related black
      yeasts.

PMID- 9776828
TI  - The identification and phylogenetic relationship of pathogenic species of
      Aspergillus based on the mitochondrial cytochrome b gene.
AB  - To study the identification and phylogeny of pathogenic isolates of Aspergillus,
      we designed primers from known cytochrome b amino acid sequences. Using these
      primers, 426 bp fragments of a mitochondrial (mt) cytochrome b gene were
      amplified by polymerase chain reaction (PCR), directly sequenced, and compared
      among Aspergillus fumigatus, A. flavus, A. niger, A. terreus and Emericella
      nidulans. Except for E. nidulans, all strains produced the 426 bp fragment by
      PCR. The E. nidulans strains demonstrated both an intron-presence fragment (
      approximately 1500 bp) and intron-absence fragment (426 bp). Species-specific
      nucleotides were found in each of the five species. Based on sequence analysis,
      the strains were further divided into several groups within each species. When a
      142-amino-acid sequence was estimated from the 426 bp nucleotide sequence using
      the yeast mt genetic code, the amino acid sequences showed no difference among
      strains of the individual species. DNA-based phylogenetic and amino acid-based
      trees were constructed. In conclusion, the DNA sequences of the cytochrome b gene
      may be of use in identification of pathogenic Aspergillus species and the amino
      acid-based tree suitable for discussing their phylogenetic relationships.

PMID- 9776829
TI  - Concentrations of airborne Aspergillus compared to the incidence of invasive
      aspergillosis: lack of correlation.
AB  - Air sampling of the rooms and corridors of the oncology wards of the hospital was
      carried out over a 54-week period to assess the concentration of viable
      Aspergillus conidia. A. fumigatus and A. flavus were recovered at a mean of 1.83
      cfu m-3 air sampled. Individual samplings yielded concentrations of up to 11.6
      cfu m-3. Other Aspergillus spp. were recovered at a mean of 2.38 cfu m-3 (maximum
      32.6 cfu m-3). Concentration was not correlated with season or hospital ward.
      Review of autopsy results showed an average of 6.6 cases of aspergillosis
      annually over a 22-year period. No seasonal variation in case incidence was
      found. Six cases of invasive aspergillosis were diagnosed on the three cancer
      wards during the air-sampling period, but no association was seen linking these
      cases with changes in recovery of airborne Aspergillus. A seasonal pattern was
      not observed in the overall incidence of aspergillosis cases nor concentrations
      of airborne conidia.

PMID- 9776830
TI  - Specific identification of Penicillium marneffei by a polymerase chain
      reaction/hybridization technique.
AB  - Penicillium marneffei has been described recently as a cause of an emerging
      mycotic infection in HIV-infected patients. A PCR/hybridization assay was
      developed to rapidly identify this pathogen. The nucleotide sequence of the 631
      bp region of 18S ribosomal DNA of P. marneffei was determined using the standard
      dideoxy chain termination method. An oligonucleotide probe was designed on the
      basis of the analysed sequences of P. marneffei and 18S rDNA sequences of other
      fungi in the GenBank database. A 631-bp PCR product was amplified using primers
      RRF1 and RRH1 from P. marneffei and seven other fungi, Penicillium spp.,
      Aspergillus fumigatus, A. flavus, Histoplasma capsulatum, Cryptococcus
      neoformans, Candida albicans and C. krusei. A 15 oligonucleotide segment (Pm3)
      which was specific for P. marneffei was synthesized and used as a probe. Only the
      PCR products of P. marneffei isolates hybridized with the Pm3 oligonucleotide
      probe. The sensitivity of the assay was approximately 0.5 pg/microl and 0.1
      pg/microl of DNA by PCR and Southern hybridization, respectively. The usefulness
      of this method as a diagnostic tool will require further studies.

PMID- 9776831
TI  - Antihistoplasmal in vitro and in vivo effect of Lys-Nva-FMDP.
AB  - The new synthetic antifungal agent, L-Lysyl-L-Norvalyl-FMDP, inhibits growth of
      the yeast form of Histoplasma capsulatum. The compound is transported into the
      fungal cells by peptide permeases, cleaved intracellularly to constitutive amino
      acids, and the released C-terminal amino acid inhibits glucosamine-6-phosphate
      synthase. Promising antihistoplasmal in vivo activity of the FMDP-peptide was
      observed in an organ load test in mice.

PMID- 9776832
TI  - Pradimicin therapy of disseminated Candida tropicalis infection in the mouse.
AB  - BMS 181184 (BMS), an analogue of pradimicin, was administered intravenously to
      neutropenic mice infected with either a fluconazole-susceptible or a fluconazole
      resistant clinical isolate of Candida tropicalis. BMS prolonged survival at doses
      >3 mg kg -1 day-1, and at higher doses reduced tissue counts in mice. BMS was
      less potent mg for mg than amphotericin B. Combined BMS and amphotericin B were
      no more effective than either of the individual drugs.

PMID- 9776833
TI  - Analysis of HLA association in susceptibility to infection with Cryptococcus
      neoformans var. gattii in a Papua New Guinean population.
AB  - The possible association between susceptibility to infection with Cryptococcus
      neoformans var. gattii and HLA phenotype was examined in a group of Papua New
      Guinean patients. There was no evidence for a statistically significant
      association between susceptibility to infection and HLA class I and HLA class II
      phenotypes, although analysis of data which had not been subjected to the
      appropriate Bonferroni correction factor suggested a trend for susceptibility
      linked to HLA B*5601.

PMID- 9776834
TI  - Role of the capsule in microglial cell-Cryptococcus neoformans interaction:
      impairment of antifungal activity but not of secretory functions.
AB  - Using two isogenic strains of Cryptococcus neoformans, we studied the influence
      of the capsule in C. neoformans microglial-cell interaction. We demonstrate that
      the acapsular mutant yeasts (CAP67) are more susceptible to phagocytosis and
      killing than encapsulated yeasts (B3501) by the murine microglial cells, BV-2. RT
      PCR analysis showed that the pattern of gene transcripts for tumour necrosis
      factor alpha (TNF-a), interleukin (IL)-1beta, IL-6, IL-12p40 and granulocyte
      macrophage colony stimulating factor remains unchanged following BV-2 cell
      infection with CAP67 or B3501 yeasts. Moreover, no induction of TNF-alpha
      secretion occurs in BV-2 cells infected with either B3501 or CAP67 yeasts or
      exposed to glucuronoxylomannan (GXM) or galactoxylomannan (GalXM). Nevertheless,
      lipopolysaccharide-induced TNF-alpha secretion is downregulated by cell infection
      with B3501 or CAP67 yeasts or exposure to GXM or GalXM. Overall, by means of a
      continuous cell line, it appears that the C. neoformans capsule is detrimental to
      microglial cell antifungal activity, while no effect can be attributed to the
      capsule as trend of cytokine gene expression and TNF-alpha secretion.

PMID- 9776835
TI  - Effect of Pichia anomala killer toxin on Candida albicans.
AB  - The effect of a Pichia anomala killer toxin upon a Candida albicans-sensitive
      strain was studied. Yeast and hyphae, after treatment with the toxin, were less
      capable of uptaking either [3H]-uridine or [35S]-methionine. In addition, the
      hyphal form of the fungus appeared to be less capable of DNA synthesis after
      toxin treatment. No effect of the killer toxin was shown upon a natural resistant
      mutant of the source strain. These data suggest that, similar to other killer
      yeast toxins, the toxin of P. anomala can produce a number of quantifiable
      effects upon sensitive C. albicans cells.

PMID- 9776836
TI  - Characterization of a single group I intron in the 18S rRNA gene of the
      pathogenic fungus Histoplasma capsulatum.
AB  - A 425-bp insertion in Histoplasma capsulatum strain G186B, denoted as Hc.SSU.1,
      was identified as a group I intron, based on the presence of the conserved
      sequence elements P, Q, R and S and a predicted secondary structure consistent
      for group I introns. The Hc. SSU.1 sequence from strain G186B was identical to
      strain G184B but differed from strain FLs1 by five nucleotides. Hc.SSU.1 was most
      similar to the group I intron from the black mould Exophiala castellanii.
      Southern blot analysis suggests that the intron is not dispersed in the genome
      and that most, if not all 18S rRNA genes harbour the intron. Northern blots
      demonstrated absence of the intron from mature 18S rRNA. A Hc.SSU.1-specific PCR
      assay detected the intron in six of 37 isolates of Histoplasma. Hc.SSU.1
      containing strains exhibited no significant differences in antimicrobial
      susceptibilities when compared to isolates not containing Hc.SSU.1. This
      investigation demonstrates the existence of group I intron sequences in the H.
      capsulatum genome and its evolutionary relationship among other group I intron
      sequences.

PMID- 9776837
TI  - Epidemiology of Candida albicans isolates from heroin addicts analysed by DNA
      typing.
AB  - Candida albicans is a ubiquitous commensal organism of humans. Several studies
      have examined outbreaks of candidiasis in heroin addicts utilizing a variety of
      methods to assess the epidemiological relatedness of the isolates and suggested
      the association of certain subtypes with disease in this patient population. The
      aim of the present study was to assess a separate group of isolates of C.
      albicans from heroin addicts in Spain using a DNA typing method. Results showed
      that, of the 34 isolates from heroin addicts, 20 were in subgroup IA, 10 were in
      subgroup IB and no isolates were of the subtype IA2. In addition, four isolates
      were in a recently described subgroup IC. Control isolates from the same
      geographical region (Spain) showed a distribution similar to the Spanish heroin
      addict isolates (12 subgroup IA, three subgroup IB, two subgroup IC and no
      isolates of the subtype IA2). In this study isolates from the same locality
      appeared similar irrespective of the patient population from which they were
      isolated. These results indicated that there may be differing geographical
      diversity of C. albicans than has previously been reported and that the newly
      described genotypic subgroup (IC) of C. albicans may be more widespread than
      previously shown.

PMID- 9776838
TI  - rDNA-RFLP and ITS1 sequencing of species of the genus Fonsecaea, agents of
      chromoblastomycosis.
AB  - Amplicons of SSU and ITS1+2 rDNA of 13 strains of Fonsecaea pedrosoi and three
      strains of F. compacta were digested with seven restriction enzymes. In addition,
      the ITS1 region of 14 strains was sequenced. With both methods significant
      variation was found which, however, did not coincide with established species
      limits based on morphology.

PMID- 9776839
TI  - Damage to yeast cells of Cryptococcus neoformans by voriconazole and fluconazole:
      a culture and microscopic study.
AB  - A systematic cultural, cytological and microscopic study of voriconazole (VCZ)
      and fluconazole (FCZ) damage to Cryptococcus neoformans over time was made. When
      haemocytometer counts were compared with colony-forming units (cfu) viability
      decreased with increased drug concentration and prolonged treatment time up to 48
      h. Percentage viability by vital staining correlated with cfu. Concentrations of
      VCZ were found to be 10-fold more potent than FCZ. At 72 h, percentage viability
      increased in cultures with lower drug concentrations, indicating outgrowth of
      surviving yeast cells. Drug treatment resulted in a cytological change in a large
      percentage of yeast cells characterized by a large central vacuole easily
      observed microscopically. Vital staining showed that there was no direct
      relationship between cytological changes and non-viability. These novel findings
      add a new approach for studying the antifungal action of VCZ and FCZ against C.
      neoformans and provide a new perspective on their antifungal action.

PMID- 9776840
TI  - In vitro activity of terbinafine against clinical isolates of dermatophytes.
AB  - A broth macrodilution method following the recommendations established by the
      National Committee for Clinical Laboratory Standards was employed for testing
      terbinafine against 20 clinical isolates of dermatophytes belonging to seven
      species. The minimal inhibitory concentrations resulting in either 80% or 100%
      inhibition of growth, compared to growth in drug-free control tubes, ranged from
      </=0.03 to 0.25 g ml-1 and from </=0.03 to 2.0 g ml-1, respectively. Terbinafine
      was shown to be fungicidal at a concentration of </=1.0 microg ml-1 for 19
      isolates. No differences in susceptibilities were found between strains isolated
      from HIV-positive and -negative individuals.

PMID- 9776841
TI  - In vitro activity of voriconazole against selected fungi.
AB  - Fifty-nine isolates consisting of 14 genera and 33 species of ascomycetes,
      basidiomycetes, and zygomycetes were tested against amphotericin B, fluconazole,
      itraconazole and voriconazole using an in vitro modified macrobroth dilution
      procedure based upon the NCCLS M27-A standard method for yeasts. The triazoles
      voriconazole and itraconazole had similar MIC values, except for Acremonium
      alabamensis, A. strictum, Fusarium oxysporum, F. solani and Wangiella
      dermatitidis, which had substantially lower voriconazole MIC values. Voriconazole
      MIC values were lower than those for itraconazole for the 17 species of
      Trichosporon tested. Fluconazole had high MIC values, often greater than 128
      microg ml-1.

PMID- 9776843
TI  - Comments on Microsporum canis.

PMID- 9776842
TI  - In vitro evaluation of terbinafine and itraconazole against dematiaceous fungi.
AB  - Two hundred and three isolates representing 15 species of filamentous ascomycetes
      were evaluated against terbinafine and itraconazole using a modification of the
      NCCLS M27-A standard reference method for yeasts. The MIC ranges and geometric
      means were similar, although terbinafine tended to have the lowest values. The
      loculoIascomycete clade tested had consistently low MIC geometric mean values for
      its members, ranging from 0.03 to 0.17 microg ml-1 for terbinafine and 0.03-0.37
      microg ml-1 for itraconazole.

PMID- 9776844
TI  - Response to 'Comments on microsporum canis' 

PMID- 9776845
TI  - Editorial: the 1996 lifetime achievement award 

PMID- 9776846
TI  - The mast cell-nerve axis in wound healing: a hypothesis.
AB  - Beyond their classic roles in allergic reactions and defence against parasites,
      mast cells can now be viewed as key players in regulating connective tissue
      homeostasis. There is good evidence that mast cells are in close morphological
      and functional contact with the peripheral nervous system. Although substantial
      differences exist between mast cells of different tissues and different species,
      they produce a wide range of agents, including cytokines, growth factors, and
      other regulatory molecules, and they respond to an equally wide range of
      substances, including neuropeptides. At our current level of understanding wound
      healing, inflammation plays a central role in this process, with macrophages
      being central protagonists at the cellular level. There is now increasing
      evidence that mast cells are also involved in wound healing, in health and
      disease. They produce and secrete histamine, heparin, and multifunctional
      cytokines and growth factors, which represent important agents in the wound
      healing process. Reviewing the recent literature supporting this hypothesis, we
      also outline the clinical importance of this work to help close the gap between
      basic research and clinical application.

PMID- 9776847
TI  - Epidemiological study of chronic dermal ulcers in China.
AB  - A total of 30,000 hospitalized surgical patients in 15 hospitals were screened
      for chronic ulcers. A total of 489 patients with chronic dermal ulcers were found
      with their major causes of ulceration including traumatic wounds, infections,
      diabetes mellitus, and venous diseases. Patients with chronic ulcers following
      trauma and infection comprised 67.48% of the total patient population. The
      incidence of diabetic ulcers and venous ulcers was 4.91% and 6.54% respectively.
      Sites of ulceration differed with different etiological factors. The percentage
      of chronic dermal ulcers in the lower extremities, upper extremities, thorax and
      abdomen, back, and head was 63.10%, 17.93%, 7.76%, 4.83% and 6.38% respectively.
      Of the 489 patients with chronic ulcers, 183 were farmers (37.42%), and 131 were
      workers (26.79%). Chronic dermal ulcers were more common in men than in women,
      but there was no significant difference in the sex-related prevalence. According
      to these data from different hospitals, the incidence of chronic ulcers in
      patients hospitalized for surgery was 1.5% to 3.0%. These data have primarily
      shown the prevalence and clinical characteristics of chronic ulcers in
      hospitalized patients in China. These data may not be consistent with reports
      from other countries. Significant differences in etiological factors of
      ulceration, professional distribution of patients with chronic dermal ulcers, and
      treatment methods were found when compared with reports of studies conducted in
      developed countries. Our results will benefit not only additional basic research,
      but these data will also be useful in preventing and managing chronic wounds in
      developing countries.

PMID- 9776848
TI  - p53 and apoptosis alterations in keloids and keloid fibroblasts.
AB  - Keloids are the result of a dysregulated wound-healing process and are
      characterized by formation of excess scar tissue that proliferates beyond the
      boundaries of the inciting wound. In this study, we investigated the expression
      of key proteins involved in regulating apoptosis in keloids. Twenty archival
      paraffin-embedded keloid samples were randomly selected for an immunoperoxidase
      assay with antibodies against fas, p53, bcl-2, and bcl-x proteins using the
      target antigen-retrieval technique. Apoptosis was assessed in keloids and normal
      skin and in keloid and normal fibroblasts by the TdT-mediated dUTP nick-end
      labeling (tunel) assay on tissue sections, fibroblast cultures, and by flow
      cytometry for cell suspensions. We found that 18 of 20 keloids expressed p53
      protein; bcl-2 was expressed by keloid fibroblasts in 19 of 20 keloids, and all
      specimens had prominent fas expression throughout the tissue. The distribution of
      these three antigens was regional within each lesion and followed a consistent
      pattern of p53 and bcl-2 expression colocalized to the hypercellular, peripheral
      areas of each keloid in a perinuclear pattern (p < .001). In contrast, an inverse
      distribution of fas expression was shown, with staining being more diffuse across
      the cell surfaces and limited to the central, more hypocellular regions in16 of
      17 keloids (p < .001). There was no specific staining pattern in these keloids
      with antihuman bcl-x. In vitro studies on cultured keloid fibroblasts (derived
      from six patients) revealed maintenance of the p53+, bcl-2+ phenotype up to
      passage 10. Neither neonatal nor normal adult skin fibroblasts expressed either
      antigen but could be induced to express p53 by exposure to adriamycin. Keloid
      lesions and keloid fibroblasts were found to have lower rates of apoptosis than
      normal controls. Keloid fibroblasts displayed enhanced apoptosis rates in
      response to hydrocortisone, gamma interferon, and hypoxia treatment as compared
      with normal adult fibroblasts. Focal dysregulation of p53 combined with
      upregulation of bcl-2 may help produce a combination of increased cell
      proliferation and decreased cell death in the younger, hypercellular areas of the
      keloid. This phenotype is reversed in the older areas of the keloid and may
      prevent malignant degeneration, thus favoring normal apoptosis as evidenced by
      prominent fas expression.

PMID- 9776849
TI  - Fibroblast senescence in pressure ulcers.
AB  - Pressure ulcers appear as localized chronic wounds in the middle of normal
      functioning skin. This study focuses on pressure ulcer fibroblasts cultured from
      the ulcer bed, ulcer margin, and normal, nonulcerated skin adjacent to the wound.
      From these areas we show that pressure ulcer fibroblasts become prematurely
      senescent. Verification of senescence was based on failure of cell populations to
      undergo a 0.5 population doubling after 1 week in culture, light microscopic
      appearance of late-passage senescent cells in culture, light microscopic
      verification of senescence in vivo and in vitro by anti-terminin staining, and
      ultrastructural identification of senescent fibroblasts by anti-terminin
      colloidal gold labeling. Although not all ulcer fibroblasts are senescent, there
      is a range of proliferative ability. The senescent phenotype of ulcer fibroblasts
      remains intact in vitro as these cells remain viable but are unable to complete
      DNA synthesis. Fibroblast senescence is not uniform in chronic wounds but varies
      within areas of the ulcer bed and from patient to patient. Although ulcer
      fibroblasts exhibit limited proliferative ability, fibroblasts from the ulcer
      margin and adjacent normal skin show a continued ability to divide. However, in
      all areas of the wound, the mean generation time of the fibroblast population is
      longer than commonly observed for cultured human diploid fibroblasts. At first
      passage, the mean generation time for fibroblasts from all patients is
      significantly different (p = .001, analysis of variance) among fibroblasts from
      the ulcer bed (4.2 2.2 days), ulcer margin (2.9 +/- 1.3 days), and adjacent
      normal skin (1.9 +/- 0.6 days). Analysis of the three cell groups by the post hoc
      Tukey test, using corrected p values shows that the difference between mean
      generation times among fibroblast populations from adjacent normal skin and ulcer
      bed are significantly different (p < 0.05), whereas the difference between
      fibroblasts from adjacent normal skin and ulcer margin and ulcer margin and ulcer
      bed are not significantly different (p > 0.05). These data may help to explain
      the poor response of certain pressure sores to aggressive medical treatment.

PMID- 9776850
TI  - Efficient debridement of necrotic wounds using proteolytic enzymes derived from
      Antarctic krill: a double-blind, placebo-controlled study in a standardized
      animal wound model.
AB  - Wound healing can be accelerated by removing necrotic tissue. Various methods of
      wound debridement have been developed, including enzymatic debridement. Recently
      potent proteolytic enzymes were isolated from the intestine of Euphausia superba
      (Antarctic krill) that might be useful for degrading necrotic tissue. The purpose
      of this study was to evaluate the debriding properties of krill enzymes, using a
      specially designed animal model and a computerized analysis system. In 10 female
      domestic pigs, each weighing 20 kg, 6 artificial ulcers were made on each
      animal's back using electrokeratome, followed by application of trichloracetic
      acid. Ulcers were treated twice daily for 7 days with either krill enzymes at
      different concentrations or with saline. Reduction of necrotic tissue was
      measured daily using computerized wound analysis. Histological examination
      included the determination of bromodeoxyuridine incorporation in order to detect
      cell proliferation as well as routine stains. The debriding effect of krill
      enzymes at a concentration of >/= 3.0 casein units per ml was significantly
      better than saline control treatment (p < 0.05). The effect was dose dependent,
      and granulation tissue formation was enhanced. In conclusion, krill enzymes are
      effective in wound debridement, as measured in this animal model.

PMID- 9776851
TI  - Expression of Wnt genes in early wound healing.
AB  - The Wnt family of developmental genes has previously been shown to be involved in
      proliferation, differentiation, and cell to cell signaling during embryogenesis.
      In addition, several Wnt genes have been shown to be expressed during
      carcinogenesis. We have investigated these genes during the wound-healing
      process. Wnt-4 gene expression is found in mouse wounds from 2 hours to 30 hours
      postwounding. The expression of Wnt-4 is also stimulated by direct trauma to
      murine fibroblasts in culture, and the expression is greatly enhanced by the
      addition of a short plasmin digest of fibrin. Therefore the regulation of Wnt-4,
      appears to be complex, with expression being stimulated both by direct trauma and
      by the influence of clotting and fibrinolysis products. We propose that the
      expression of Wnt-4 in the early wound, in response to the provisional fibrin
      matrix, regulates cell movement and proliferation in the creation of new tissue
      by mechanisms related to those of embryogenesis.

PMID- 9776852
TI  - Bioactive factors affect proliferation and phenotypic expression in progenitor
      and pluripotent stem cells.
AB  - Progenitor and pluripotent stem cells reside within connective tissue
      compartments. They are also present in granulation tissue. This study examined
      the effects of treating these two cell populations with eight bioactive factors.
      Cells were assayed for DNA content as a measure of proliferation and for tissue
      specific phenotypic markers as measures of lineage progression and lineage
      commitment. Platelet-derived endothelial growth factor and insulin-like growth
      factor-II did not induce proliferation in either population. However,
      dexamethasone, insulin, insulin-like growth factor-I, muscle morphogenetic
      protein, platelet-derived growth factor-AA, and platelet-derived growth factor-BB
      stimulated proliferation in one or both cell populations. Platelet-derived growth
      factor-BB was the most potent stimulator of proliferation in either population.
      Phenotypic expression markers were induced in the progenitor cells by insulin,
      insulin-like growth factor-I, insulin-like growth factor-II, dexamethasone, and
      muscle morphogenetic protein. However, only dexamethasone and muscle
      morphogenetic protein induced phenotypic expression markers in the pluripotent
      cells. Platelet-derived endothelial cell growth factor, platelet-derived growth
      factor-AA, and platelet-derived growth factor-BB did not induce phenotypic
      expression markers in progenitor or pluripotent cells. This study suggests the
      potential for using progenitor and pluripotent cells as an in vitro model to
      ascertain the effects of various bioactive factors on stem cells potentially
      involved in tissue maintenance and repair.

PMID- 9776853
TI  - A new paradigm for wound care.

PMID- 9776854
TI  - Ultrasound therapy in chronic leg ulceration: a meta-analysis.
AB  - We reviewed all articles on ultrasound therapy published since 1950 to assess the
      evidence for an effect of this therapy in the treatment of chronic leg ulcers.
      Fourteen studies concerning ultrasound therapy, chronic leg ulcers, and wound
      healing were found. The six studies that fulfilled inclusion criteria for a
      randomized controlled trial were generally found lacking with respect to
      description of ulcer etiology-treated area, ultrasound head area, control of
      ultrasound apparatus, sham ultrasound apparatus, and follow-up evaluations.
      However, all six studies presented their data in a way that made pooling possible
      with respect to a decrease in ulcer area as a percent of the starting area. A
      standardized effect size was applied and gave evidence for a significant effect
      of ultrasound, showing a 16.9% (CI95: 6.3% to 27.5%, p = 0.011) mean difference
      in healing after 4 weeks of treatment and a 14.5% (CI95: 6.6% to 22.3%, p =
      0.005) mean difference after 8 weeks of treatment compared with control
      treatment. In three studies, the number of healed ulcers was assessed, and
      pooling showed a nonsignificant (p = 0.06) therapeutic gain of 15% (CI95: 1% to
      30%). This analysis would suggest that ultrasound has the best effect being
      delivered in low doses around the edge of the ulcer, but further studies are
      required to confirm this possible effect and to evaluate a possible dose-response
      relationship.

PMID- 9776855
TI  - Dynamics of the matrix metalloproteinases MMP-1 and MMP-8 in acute open human
      dermal wounds.
AB  - Extracellular matrix degradation during dermal wound healing involves multiple
      levels of regulation by several enzymes of the matrix metalloproteinase family,
      their activators, and their inhibitors. This study tested the hypothesis that a
      temporal pattern of interstitial collagenase appearance occurs during normal
      dermal wound healing, with matrix metalloproteinase-8 originating from
      neutrophils appearing earlier than the fibroblast-derived matrix
      metalloproteinase-1. Open (6 mm) full-thickness dermal wounds, which were covered
      by transparent occlusive dressings, were made in healthy human volunteers (n =
      20). Wound fluids from under the dressings were collected daily through day 8,
      and wound tissue biopsies were obtained on days 0, 2, 4, 14, and 28. Collagenases
      were extracted from homogenized tissue biopsies for analysis. Samples were
      analyzed for the presence of matrix metalloproteinase-1 and matrix
      metalloproteinase-8 by enzyme-linked immunosorbent assays and by collagenase
      activity assays using purified types I and III collagen as substrates. In
      addition, tissue inhibitor of metalloproteinases-1 and matrix metalloproteinase
      1/tissue inhibitor of metalloproteinases-1 complexes in wound fluids were
      measured. Results showed a differential temporal pattern of matrix
      metalloproteinase-1 and matrix metalloproteinase-8 in wound exudates with peak
      levels of matrix metalloproteinase-8 occurring on day 4 and matrix
      metalloproteinase-1 peak levels on day 7. Maximal levels in tissue for both
      enzymes occurred on day 2. At all time points examined, levels of matrix
      metalloproteinase-8 were statistically higher than matrix metalloproteinase-1
      (100-fold to 200-fold). Tissue inhibitor of metalloproteinases-1 levels declined
      over time, whereas levels of matrix metalloproteinase-1/tissue inhibitor of
      metalloproteinase-1 complexes increased to a plateau on day 7. This study
      provides new evidence implicating matrix metalloproteinase-8 as a major
      collagenase in healing human dermal wounds. It also shows a temporal pattern in
      the appearance of the matrix metalloproteinases, tissue inhibitor of
      metalloproteinase-1, and matrix metalloproteinase-1/tissue inhibitor of
      metalloproteinases-1 complexes, suggesting that a tightly regulated pattern of
      expression of matrix metalloproteinases and their inhibitors is essential for
      normal wound healing in humans.

PMID- 9776856
TI  - Inhibited proliferation of fibroblasts derived from chronic diabetic wounds and
      normal dermal fibroblasts treated with high glucose is associated with increased
      formation of l-lactate.
AB  - Diabetes is accompanied by delayed wound healing and insufficient granulation
      tissue formation, possibly because of a defect in fibroblast function. We have
      previously shown that fibroblasts derived from chronic diabetic foot ulcers have
      lower proliferation compared with those from uninjured skin. The aim of this
      study was to investigate possible mechanisms explaining the impaired fibroblast
      proliferation observed in fibroblasts from non-insulin-dependent diabetes
      mellitus chronic wounds and normal fibroblasts cultured in high glucose.
      Fibroblasts from two groups of patients were studied: nondiabetic patients with
      chronic venous stasis ulcers and non-insulin-dependent diabetes mellitus patients
      with chronic diabetic wounds. Biopsies from both uninjured skin and wounds were
      taken from the same patients to serve as sources of fibroblasts. A fluorometric
      method was used to determine DNA content, and a spectrophotometric lactate
      oxidase method was used for lactate level analysis. We found a dose-dependent
      inhibition of normal fibroblast proliferation when adding conditioned media from
      non-insulin-dependent diabetes mellitus wound fibroblasts. The conditioned
      medium, from these cells showed elevated l-lactate levels, 6.3 +/- 0.7 mmol/L,
      compared with media derived from nondiabetic, 2.1 +/- 0.3 mmol/L (p < 0.01), and
      diabetic uninjured skin fibroblasts, 3.5 +/- 0.6 mmol/L, and from chronic
      nondiabetic wound fibroblasts 2.9 +/- 0.3 mmol/L. Addition of 6 mmol/L l-lactate
      to uninjured normal fibroblasts resulted in decreased DNA content (58 +/- 7%, p <
      0.01). Previously we have shown that high glucose concentrations inhibit
      fibroblast proliferation and induce growth factor resistance. When increasing the
      amount of d-glucose in the media, l-lactate levels increased in all cell types.
      When the uninjured normal cells were treated with beta-hydroxybutyrate, the total
      DNA content decreased by 42 +/- 5% (p < 0.05), with no significant increase in
      the l-lactate levels. These observations indicate that l-lactate production may
      be of importance for fibroblast proliferation in vitro and may play a role in
      fibroblast proliferation in vivo.

PMID- 9776857
TI  - Expression of inducible nitric oxide synthase in human burn wounds.
AB  - Nitric oxide is produced by various cell types and can initiate either beneficial
      or deleterious effects. Because cultured human keratinocytes express an inducible
      isoform of nitric oxide synthase, it was postulated that keratinocytes within a
      burn wound would express increased levels of inducible nitric oxide synthase
      following the injury. Immunohistochemical staining identified the sites of
      cellular expression and temporal sequence of inducible nitric oxide synthase
      protein within partial- and full-thickness burns excised from 29 patients. While
      migrating keratinocytes at the immediate edge of the wounds showed decreased or
      undetectable levels of inducible nitric oxide synthase, the immediately adjacent
      proliferative population and upwardly growing keratinocytes from surviving hair
      follicles showed increasingly greater cytoplasmic staining for inducible nitric
      oxide synthase at 4-21 days after injury. Noninjured skin showed minimal
      inducible nitric oxide synthase staining. Within the wound, detectable inducible
      nitric oxide synthase protein appeared to decrease as keratinocytes assumed a
      differentiated phenotype in the outer newly resurfaced epidermis, in inner root
      sheath layers of hair follicles, or in epithelium of eccrine sweat ducts. Within
      granulation tissue, immunoreactive inducible nitric oxide synthase was detected
      in capillary endothelium and in arterial smooth muscle layer. Focal increases in
      inducible nitric oxide synthase expression were noted in association with
      inflammatory infiltrates. In conclusion, the cellular and temporal distributions
      of immunoreactive inducible nitric oxide synthase suggest that nitric oxide may
      play a role in the regulation of wound repair processes beyond the acute burn
      injury.

PMID- 9776859
TI  - Ultrastructural changes during contraction of collagen lattices by ocular
      fibroblasts.
AB  - Contraction and scarring of the cornea and conjunctiva following disease or
      injury are major causes of visual morbidity. The aim of this study was to
      identify any specific ultrastructural features of ocular fibroblast behavior in
      different collagen lattices in order to understand some of the mechanisms of cell
      mediated contraction. Normal human Tenon's capsule fibroblasts were cultured
      within both restrained and floating collagen lattices for periods of up to 13
      days and then analyzed using transmission electron microscopy. The contractile
      force of these fibroblasts was also tested using the culture force monitor, an
      instrument capable of measuring the minute forces exerted by cells within a
      collagen lattice. The results showed differences in the behavior of fibroblasts
      cultured in the two gel models. The features seen in restrained gels suggest that
      fibroblasts were actively migrating across and through the lattice. These
      migratory features were not seen to the same extent in untethered gels, which
      lack the inherent tension and support of the tethered model. We hypothesize that
      contraction of the collagen matrix in tethered lattices is due to cellular
      migration and that this fact cannot be ascertained from untethered gels. Both
      lattice models have experimental value, but it is important to appreciate what
      mechanical signals cells receive from the matrix in order to understand cellular
      behavior.

PMID- 9776858
TI  - Nonviable Staphylococcus aureus and its peptidoglycan stimulate macrophage
      recruitment, angiogenesis, fibroplasia, and collagen accumulation in wounded
      rats.
AB  - We have previously shown that local application at the time of operation of
      Staphylococcus aureus, nonviable S. aureus, its cell wall, or S. aureus
      peptidoglycan accelerates wound healing. We hypothesized that this effect is due
      to both direct and indirect mechanisms, among which is an increase in the
      inflammatory response to wounding, resulting in an increase in macrophages,
      angiogenesis, and fibroblasts. Twenty-seven Sprague-Dawley male rats were
      anesthetized, and two 7-cm paravertebral skin incisions were made. Four polyvinyl
      alcohol sponges, two on each side, containing either 100 microliter of isotonic
      saline or 0.5 mg of nonviable S. aureus or S. aureus peptidoglycan in 100
      microliter saline were implanted subcutaneously. Nonviable S. aureus or S. aureus
      peptidoglycan (860 microgram/cm incision) in 200-microliter saline were
      inoculated into the incisions at closure. The rats ate a commercial rat chow and
      drank tap water ad libitum throughout. After days 3 and 7 postwounding, rats were
      euthanized, and tissues were examined for immunohistochemical features of
      reparative tissue using ED-1, Factor VIII, and vimentin antibodies, markers for
      monocyte/macrophages, endothelial cells, and mesenchymal cells (including
      fibroblasts), respectively. Incisions treated with nonviable S. aureus or S.
      aureus peptidoglycan showed more macrophages along and deep in the wound tract 7
      days postoperatively. Nonviable S. aureus or S. aureus peptidoglycan-treated
      sponges were surrounded and penetrated by much larger capsules of reparative
      tissue than saline-treated sponges at both 3 and 7 days. Neutrophil influx was
      much greater in nonviable S. aureus or S. aureus peptidoglycan-treated sponges,
      especially in central regions, and there were many more ED-1-stained macrophages
      in distinct geographic locations, specifically, the more peripheral-cortical
      areas. Some clustering of macrophages occurred around areas of invasion by
      reparative tissue into the surrounding subcutaneous fat and within the
      interstices of the sponges at the interface between reparative tissue and acute
      inflammatory cells. In contrast, saline-treated sponge reparative tissue had
      significantly fewer macrophages, much thinner and flimsy reparative tissue, with
      proportionately fewer macrophages clustering centrally. There were many more
      mesenchymal cells (notably fibroblasts) and new blood vessels and much more
      reparative collagen in the nonviable S. aureus or S. aureus peptidoglycan-treated
      sponges. We conclude that local application of nonviable S. aureus or S. aureus
      peptidoglycan at wounding induces an increased number and alteration in location
      of macrophages, increased influx (or proliferation) of mesenchymal cells (notably
      fibroblasts), and increased angiogenesis and reparative collagen accumulation, as
      well as increasing the overall acute inflammatory response to wounding.

PMID- 9776861
TI  - 1998: a new era in wound healing and new opportunities for The Wound Healing
      Society.

PMID- 9776860
TI  - Enhancement of wound healing by curcumin in animals.
AB  - Tissue repair and wound healing are complex processes that involve inflammation,
      granulation, and remodeling of the tissue. In this study, we evaluated the in
      vivo effects of curcumin (difeurloylmethane), a natural product obtained from the
      rhizomes of Curcuma longa on wound healing in rats and guinea pigs. We observed
      faster wound closure of punch wounds in curcumin-treated animals in comparison
      with untreated controls. Biopsies of the wound showed reepithelialization of the
      epidermis and increased migration of various cells including myofibroblasts,
      fibroblasts, and macrophages in the wound bed. Multiple areas within the dermis
      showed extensive neovascularization, and Masson's Trichrome staining showed
      greater collagen deposition in curcumin-treated wounds. Immunohistochemical
      localization of transforming growth factor-beta1 showed an increase in curcumin
      treated wounds as compared with untreated wounds. In situ hybridization and
      polymerase chain reaction analysis also showed an increase in the mRNA
      transcripts of transforming growth factor-beta1 and fibronectin in curcumin
      treated wounds. Because transforming growth factor-beta1 is known to enhance
      wound healing, it may be possible that transforming growth factor-beta1 plays an
      important role in the enhancement of wound healing by curcumin.

PMID- 9776862
TI  - Perspective article: collagen expression by novel cell populations in the dermal
      wound environment.
AB  - Numerous collagenous structures must be reconstituted following injury to the
      skin in order to return function to this tissue. The basement membrane zone,
      vascular basement membranes, and the dense connective tissue of the dermis are
      examples of structures that contain a number of different collagen types and that
      may need replacement following injury. In addition, a scar is deposited at the
      site of damage in order to substitute for elements lost in the trauma and for
      elements that cannot be successfully replaced. Clearly, cells resident within the
      different compartments of the skin are able to synthesize and deposit collagen to
      reform these multiple structures. However, accumulating experimental evidence
      suggests that in addition to these resident cells, blood-borne cells may be
      responsible for the deposition of a portion of the newly synthesized collagen.
      Studies from this laboratory point to the activated monocyte as a potential
      source of collagen in the wound environment. Given the dynamics of the process,
      the hypothesis is proposed that during normal wound healing, the activated
      monocyte is a source of collagen essential for the rapid formation of a
      provisional matrix conducive for the subsequent formation of granulation tissue.
      Collagen synthesis also occurs by expanded populations of resident cells, under
      the influence of inflammatory cell-derived mediators, which results in the major
      accumulation of collagen during normal wound repair. However, if a chronic
      inflammatory state is initiated, the activated monocytes may remain in sufficient
      numbers to deposit collagen leading to a pathological lesion.

PMID- 9776863
TI  - Sympathetic denervation impairs epidermal healing in cutaneous wounds.
AB  - The involvement of peripheral nerves in dermal wound healing, particularly in the
      inflammatory response has not been extensively studied. Therefore, this study was
      performed to examine the role of peripheral nerves in the healing of rat skin
      linear incisions. We report that chemical sympathectomy with 6-hydroxydopamine
      significantly impaired wound healing as measured on days 7, 11, and 14
      postsurgery (by day 14, 48% of the sympathectomized rats were healed in contrast
      with 84% of the controls; p = 0.0104). In contrast, neonatal capsaicin treatment,
      which predominantly destroys sensory afferents, had no effect on wound healing (p
      > 0.05 on all days). These results support the hypothesis that sympathetic
      efferents are important for wound healing. Unlike previous research, which showed
      that peripheral nerves influence ischemic skin flaps, we are the first to
      demonstrate a role for peripheral nerves in the healing of skin incisions.
      Because inflammation is an important step in cutaneous wound healing, we propose
      that a reduction of neurogenic inflammation caused by sympathectomy may explain
      the impaired wound healing that we observed in our study.

PMID- 9776864
TI  - Effect of interferon-alpha2b on guinea pig wound closure and the expression of
      cytoskeletal proteins in vivo.
AB  - Scar contraction following the healing of deep partial-thickness or full
      thickness dermal injury is a leading cause of functional and cosmetic morbidity.
      The therapeutic use of interferon for the treatment of fibroproliferative
      disorders associated with scar contraction, including hypertrophic scar, has been
      suggested because of its antifibrotic properties. Treatment of fibroblasts with
      interferon has been shown to reduce the rate and extent of contraction using the
      in vitro fibroblast-populated collagen lattice model. In order to establish the
      effect of interferon-alpha2b on full-thickness wound contraction in vivo, osmotic
      pumps loaded with interferon or sterile saline were implanted intraperitoneally
      in guinea pigs. Seven days following implantation, six full-thickness punch
      biopsy wounds were created and were monitored by daily assessment of the wound.
      There was a significant reduction in the rate of wound contraction in the
      interferon-treated animals after day 3 (p < 0.01). Western blot analysis was used
      to quantitate selected cytoskeletal proteins in the normal skin and tissue
      biopsied from the wound at days 7, 14, and 21 postinjury. The amount of vimentin
      in the contracted wound increased following injury as compared with the amount
      present in normal skin (p < 0.0001); however, the relative amounts of the
      myofibroblast-associated cytoskeletal proteins alpha-smooth muscle actin and
      smooth muscle myosin were less than those found in normal, uninjured skin. By
      using vimentin to adjust the levels of cytoskeletal proteins for the increase in
      cellularity in the wounds, both alpha-smooth muscle actin and smooth muscle
      myosin significantly increased after closure of the wounds on day 14, as compared
      with the open-wound stage (day 7), before further reductions occurred with
      remodeling on day 21. Measurement of apoptotic cells using the terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay
      revealed an increase in apoptosis in the interferon-alpha2b-treated animals at 21
      days following wounding (p < 0.001), which did not colocalize with alpha-smooth
      muscle actin staining. Taken together, these findings suggest that interferon
      alpha2b inhibits wound contraction in vivo, not through an appreciable alteration
      in myofibroblast number or cytoskeletal protein expression, but possibly through
      a reduction in fibroblast cellularity by the induction of apoptosis.

PMID- 9776865
TI  - Effect of a collagen matrix containing epidermal growth factor on wound
      contraction.
AB  - Excessive wound contraction is known to lead to pathological wound contracture.
      Using a rabbit model, we applied a bovine type I collagen matrix sponge as a
      dermal substitute and human epidermal growth factor to full-thickness excisional
      wounds. Wound contraction was assessed 14 and 28 days after wounding. It was
      found that both collagen matrix and epidermal growth factor significantly
      inhibited wound contraction (p < 0.001) in all wounds treated with collagen
      matrix alone or treated with 0.1 and 1 microg of epidermal growth factor 28 days
      after wounding. Interestingly, the combination of collagen matrix with epidermal
      growth factor strongly inhibited wound contraction over matrix alone (p < 0.01 on
      day 28). Histological analyses showed a regular horizontal arrangement of
      collagen fibers in the dermis under wounds treated with these substances but not
      under untreated wounds. Furthermore, using a fibroblast-populated collagen gel,
      the direct inhibitory effect of epidermal growth factor on gel contraction by
      fibroblasts was also observed. Collagen gels without stimulation contracted to
      29.5 +/- 0. 6% of their original size, as determined 6 days after culturing. At 3
      days or more, epidermal growth factor inhibited collagen gel contraction by
      fibroblasts (after 6 days: 34.2 +/- 1.8%, p > 0.05; 36.5 +/- 2.8%, p < 0.05; and
      39.8 +/- 2.1%, p < 0.001 at 1, 10, and 100 ng/ml of epidermal growth factor,
      respectively). In conclusion, collagen matrix and epidermal growth factor,
      particularly in combination, may be useful in the prevention of wound
      contracture.

PMID- 9776866
TI  - Histological characterization of a delayed wound healing model in pig.
AB  - Chronic wounds, such as venous ulcers and pressure ulcers, frequently remain
      unresponsive to currently available treatments. Several animal models of wound
      healing have been published, including models of impaired healing developed to
      mimic the clinical condition of chronic wounds better. We used a delayed wound
      healing model in the pig that uses irradiation of the skin prior to creation of
      the surgical wounds and characterized it histologically. Radiation was used on
      one side of the back prior to making four full-thickness wounds on each side.
      Clinical observations were performed to record granulation tissue,
      reepithelialization, and wound area as a function of time. Histology data were
      obtained at 1, 2, 3, and 4 weeks, and slides were stained with hematoxylin and
      eosin for general observations. Immunohistochemistry was performed using laminin
      as a marker for blood vessels, and the number, size, and circularity of blood
      vessels found in the granulation tissue were measured. Our results show that this
      model causes a delay in wound healing that is mostly apparent between days 7 and
      15. Granulation tissue took more time to form and fill the wounds on the
      irradiated side, and blood vessels were slower to develop. Blood vessels were
      larger and more irregular in shape on the irradiated side than on the control
      side. After 2 weeks, healing resumed, indicating that the induced damage was not
      irreversible. These results suggest that this model can be used to test the
      effects of therapeutic approaches intended to treat chronic wounds.

PMID- 9776867
TI  - Susceptibility of the malaria vectors to insecticides in Bangladesh.
AB  - Insecticide susceptibility tests with diagnostic dosages of 4% DDT and 5%
      malathion concentrations conducted at field sites on the two important principal
      malaria vectors namely, Anopheles dirus and An. philippinensis have been
      reported. They are found to be susceptible to DDT and malathion. The implication
      of the use of insecticides in controlling malaria is also discussed.

PMID- 9776868
TI  - Effect of Nelumbo nucifera rhizome extract on the gastrointestinal tract of rat.
AB  - Extract of Nelumbo nucifera rhizome (RNN) was used as anti-diarrheal agent to
      combat the diarrhea in experimental rats. The RNN extract in graded doses (100,
      200, 400 and 600 mg/kg body wt.) reduced not only the frequency of defecation,
      wetness of fecal dropping and PGE2 induced enteropooling but also the propulsive
      movements of charcoal meal significantly.

PMID- 9776869
TI  - Effect of Norplant on liver function.
AB  - Combined pills have known adverse effects on liver function. Progesterone based
      contraceptives are thought to be safer in this regard. The effect of Norplant, a
      levonorgestrel contraceptive implant, on liver function was evaluated in 149
      Bangladeshi women of reproductive age in this study. Liver function tests and
      ultrasonography of hepato-biliary system were done before and after the
      implantation. The patients were followed upto two years. There were non
      significant transient rise of serum bilirubin and slight enlargement of liver
      during the first year. There was no significant change in the levels of AST, ALT,
      alkaline phosphatase, total protein, albumin-globulin ratio and prothrombin time.
      The results suggest that Norplant has no adverse effect on liver function.

PMID- 9776871
TI  - Dystrophic calcification in the neck--a case report.
AB  - One 55 years aged male person was admitted with progressive painless neck
      swelling with multiple discharging sinuses. His X-ray of the neck showed a dense
      radio-opaque shadow & serum calcium level was 2 mmol/l. On neck exploration, an
      irregular calculus was revealed; hooking around the left carotid sheath.
      Histopathology confirmed the clinical diagnosis of tuberculosis. Anti-TB
      chemotherapy for six months cured him.

PMID- 9776870
TI  - An exercise training combined with dietary program for patients with
      hypertension.
AB  - A controlled clinical trial was conducted to determine whether combined exercise
      training and diet alone reduce blood pressure (BP), body weight and body mass
      index (BMI) in three weeks. Twenty eight patients with diastolic BP < or = 110
      mmHg were assigned to a hypertensive group and another 28 subjects with diastolic
      BP < or = 90 mmHg were subjected to the same intervention as control group
      (normotensive group). Exercise training and diet reduced diastolic BP by 24.7
      mmHg and systolic BP by 32.8 mmHg in hypertensive group. There was a mean
      decreased of 5.3 mmHg in the diastolic BP in the normotensive group (P < 0.001).
      The systolic BP decreased only minimally. The weight loss ranged from 1 kg to 3
      kg in hypertensive and 1 kg to 2 kg in the normotensive group. The mean weight
      loss was 1.6 kg (0.7) in hypertensive and 1.5 kg (0.5) in the normotensive group.
      In both the groups the weight reduction was highly significant (P < 0.001) and
      moderately positive correlation was also noted with the fall of BPs. The mean
      fall of BMI was 0.61 kg/m2 (0.21) and 0.51 (0.2) kg/m2 in the hypertensive and
      normotensive groups respectively. The findings indicated that a combined exercise
      training and dietary program could lower BP in patients with mild to moderate
      hypertension, but its long-term consequences on morbidity and mortality remain to
      be determined.

PMID- 9776872
TI  - The validation of its updated and rewritten nurse practitioner degree programme.

PMID- 9776873
TI  - Nurse power.

PMID- 9776874
TI  - Visiting rights.

PMID- 9776876
TI  - Child benefit.

PMID- 9776875
TI  - Pride and prejudice.

PMID- 9776877
TI  - What's new?

PMID- 9776878
TI  - Human MOTs.

PMID- 9776879
TI  - Site perfect.

PMID- 9776881
TI  - Adding spice to your life.

PMID- 9776880
TI  - Teenage health.

PMID- 9776882
TI  - Broadcast.

PMID- 9776883
TI  - The UKCC's further work on specialist practice.

PMID- 9776884
TI  - Care of skeletal pins: a literature review.
AB  - Using the literature reviewed in this article, the author explores the issues
      surrounding wound care management in relation to care of skeletal pin sites. In
      this way, an evidence-based protocol for care is developed.

PMID- 9776885
TI  - The effects of ecstasy.
AB  - Nurses working in critical care are seeing an increasing number of Ecstasy
      overdoses. This article describes the effects of Ecstasy and discusses the need
      for nurses to know more about the drug and the consequences of overdose.

PMID- 9776886
TI  - Psychosexual awareness in everyday nursing.
AB  - Using real life examples, this article shows how nurses, midwives and other
      professional carers can help patients to communicate about the way sexual
      feelings are affected by illness, childbirth and hospitalisation. Nurses need to
      special knowledge, the author argues, but need to develop confidence in their own
      ability to listen and respond.

PMID- 9776887
TI  - Dressing wounds.
AB  - This article describes the choice and method of application of wound dressing in
      a variety of situations. The types of wounds covered include those in awkward
      areas, cavity wounds and fungating wounds. The problems of patients with
      allergies to wound dressings are also discussed.

PMID- 9776889
TI  - Nurse trust in Scotland.

PMID- 9776888
TI  - Diverse market.

PMID- 9776890
TI  - Thanks for 50 years of NHS nursing.

PMID- 9776891
TI  - Wishing well. Nursing leaders share their hopes for the future of the NHS.

PMID- 9776892
TI  - Fast forward into 2048.

PMID- 9776893
TI  - Born on the 5th of July.

PMID- 9776894
TI  - Mother country.

PMID- 9776895
TI  - Great expectations.

PMID- 9776896
TI  - How support teams can develop research activity.
AB  - This report discusses an initiative whereby a research support team has been
      formed in order to encourage, support and develop research awareness and activity
      among nurses.

PMID- 9776897
TI  - The importance of hope.
AB  - Hope is an important aspect of life. Although nursing can play a part in
      encouraging hope, we seem to be in danger of neglecting this aspect of care. This
      article examines the meaning of hope, and suggests ways in which the nurse may
      inspire hope in those who need it.

PMID- 9776899
TI  - Suturing.
AB  - This article describes the nursing interventions involved in wound cleaning
      before the application of sutures, as well as the necessary wound assessment
      skills, and preparatory techniques in suturing simple lacerations of the skin.

PMID- 9776898
TI  - Promoting scope of professional practice in a large organisation.
AB  - The UKCC's Scope of Professional Practice document opened up major opportunities
      for nurses, but many have problems relating its principles to their everyday
      practice. This article describes how workshops were held in a large teaching
      trust to raise nurses' awareness of the document.

PMID- 9776900
TI  - Aloe vera: magic or medicine?
AB  - Some recent studies appear to show topical and orally administered aloe vera
      preparations in patients with chronic venous leg ulcers may aid healing. Despite
      encouraging results, in the absence of larger research studies, the author
      cautions against generalisation of this complementary treatment.

PMID- 9776901
TI  - Nursing burn wounds on general wards.
AB  - In this article, the author predicts that patients with intermediate and minor
      burn injuries will be increasingly nursed on general wards. In this context, she
      describes developments in the treatment and management of wounds caused by burns,
      and examines the advantages and drawbacks of current nursing treatments and how
      these should be used.

PMID- 9776902
TI  - New system for wheelchair users.

PMID- 9776903
TI  - National standards of service.

PMID- 9776904
TI  - Freedom of speech.

PMID- 9776907
TI  - Street fighter.

PMID- 9776905
TI  - Risky business.

PMID- 9776906
TI  - Country life?

PMID- 9776908
TI  - Lecture theatre.

PMID- 9776909
TI  - Less haste....

PMID- 9776910
TI  - Theatre trip.

PMID- 9776912
TI  - Nursing solutions.

PMID- 9776911
TI  - The man with a mission. Interview by Charlotte Alderman.

PMID- 9776913
TI  - Family rights.

PMID- 9776914
TI  - Review of care for people who are hard to engage.
AB  - Here, Ian McMillan provides a summary of the report Keys to Engagement: Review of
      Care for People with Severe Mental Illness who are Hard to Engage With (The
      Sainsbury Centre for Mental Health 1998), which discusses how patients with
      mental health problems should be encouraged to engage with community-based
      services.

PMID- 9776915
TI  - Evaluating health care using goal attainment scaling.
AB  - Goal attainment scaling, a way of evaluating the outcomes of care, was first
      discussed 30 years ago, but it is rarely used today. The author argues that the
      technique is particularly relevant to modern healthcare practice.

PMID- 9776916
TI  - Focus group interviews: defining clinical supervision.
AB  - In the companion article to a literature review published recently in Nursing
      Standard (Sloan 1998), the author demonstrates the use of focus groups as a data
      collection method. He details how the group discussion was analysed, and
      reproduces the findings relevant to the 'good characteristics' of a clinical
      supervisor from the supervisee's perspective.

PMID- 9776917
TI  - Self-medication in ophthalmology.
AB  - Patients on a short-stay ophthalmology ward are encouraged to administer their
      own medication. In this article, the author describes how standards were set to
      audit the self-medication programme.

PMID- 9776918
TI  - The urology nurse practitioner.

PMID- 9776919
TI  - The UK nursing labour market.

PMID- 9776920
TI  - First class only.

PMID- 9776922
TI  - Learning for life.

PMID- 9776921
TI  - Get in on the act.

PMID- 9776923
TI  - Size matters.

PMID- 9776924
TI  - Agency alert. Irresponsible agencies are increasingly sending incompetent carers
      to nursing homes.

PMID- 9776925
TI  - Waiting games.

PMID- 9776926
TI  - Persecution of the fifty-somethings.

PMID- 9776927
TI  - Buying healthcare.

PMID- 9776928
TI  - Opportunity knocks ... will nurses answer?

PMID- 9776929
TI  - The need for single registration care homes: the RCN vision.
AB  - This report discusses the provision of care for people living in nursing and
      residential homes. It presents the RCN's (1997a) proposals for single
      registration care homes. In the first of two articles, on page 35 in this week's
      issue, the authors also examine the statutory framework that currently regulates
      residential and nursing home provision.

PMID- 9776930
TI  - The need for single registration care homes. 1: Current provision.
AB  - As we await the government White Paper on social services, the authors examine;
      in the first of two articles, the current two-tier service which means that
      elderly people are often moved unnecessarily between residential and nursing
      homes when their health needs change. The Royal College of Nursing's proposals
      for single registration care homes is explained on pages 32 and 33 in this issue.
      The second article will appear next week.

PMID- 9776931
TI  - The use of nurses' holding power in a large psychiatric hospital.
AB  - The use of nurses' holding power is a poorly explored aspect of psychiatric
      inpatient care. This study examined the use of Section 5(4) at the Maudsley
      Hospital, London, since the introduction of the 1983 Mental Health Act. Between
      1983 and 1996 nurses' holding powers were used on 25 occasions. Seventy two per
      cent of patients detained under Section 5(4) of the Mental Health Act 1983 were
      subsequently detained under Section 5(2). Results were broadly consistent with
      previous studies, although some significant inconsistencies were observed which
      can probably be attributed to small sample sizes. Further, multicentre research
      is needed in order that substantive conclusions can be drawn.

PMID- 9776932
TI  - Patients' use of denial: coping with the unacceptable.
AB  - Nurses working with terminally ill or bereaved clients and their families need to
      understand the defence mechanism of denial and how it helps people to cope with
      unacceptable physical and psychological threats.

PMID- 9776933
TI  - Numeracy skills for intravenous calculations.

PMID- 9776934
TI  - Violence in families: assessing prevention and treatment programs.

PMID- 9776935
TI  - AHCPR focuses on information for health care decision makers.

PMID- 9776936
TI  - Long-term care research: demand, payment, and outcomes.

PMID- 9776937
TI  - The roles of Medicaid and economic factors in the demand for nursing home care.
AB  - OBJECTIVE: To examine nursing home demand, focusing on how Medicaid affects
      demand, the role of economic variables, and on important interactions between
      explanatory factors. DATA SOURCES: From the 1989 National Long Term Care Survey,
      a nationally representative sample of community-based and institutionalized
      elderly persons with disabilities (N = 3,837). Survey data are merged with state-
      and county-level data on Medicaid policy and local market conditions. STUDY
      DESIGN: Sample members are classified as Medicaid-eligible or private pay, were
      they to enter a nursing home. The probability of being in a nursing home is
      estimated separately on these two groups using probit. To explore interactions,
      these subsamples are further divided between married and unmarried persons and
      between persons with high and low levels of disability. PRINCIPAL FINDINGS:
      Demand for nursing home care systematically differs, depending on eligibility for
      Medicaid. This is attributed in part to the structure of Medicaid benefits.
      Although economic factors do not appear important to demand decisions in the
      aggregate, they play a larger role among married persons relative to unmarried
      persons, and among less disabled persons relative to highly disabled persons.
      CONCLUSIONS: Understanding the nature of nursing home demand requires careful
      consideration of the different consumption choices people face by virtue of their
      eligibility for public benefits. Because behavioral responses to changes in
      policy are found to differ among various groups of disabled persons, policymakers
      should be sensitive to how these differences affect the efficiency and
      distributional effects of specific policy changes.

PMID- 9776938
TI  - Nursing home performance under case-mix reimbursement: responding to heavy-care
      incentives and market changes.
AB  - OBJECTIVE: To examine the effect of case mix-adjusted reimbursement policy and
      market factors on nursing home performance. DATA SOURCES AND STUDY SETTING: Data
      from Medicaid certification inspection surveys, Medicaid cost reports, and the
      Kentucky State Center for Health Statistics for the years 1989 and 1991, to
      examine changes in nursing home performance stemming from the adoption of case
      mix-adjusted reimbursement in 1990. STUDY DESIGN: In addition to cross-sectional
      regressions, a first-difference approach to fixed-effects regression analyses was
      employed to control for facility differences that were essentially fixed during
      the survey years and to estimate the effects of time-varying predictors on
      changes in facility expenditures, efficiency, and profitability. PRINCIPAL
      FINDINGS: Facilities that increased the proportion of Medicaid residents and
      eliminated excess capacity experienced higher profitability gains during the
      beginning phase of case-mix reimbursement. Having a heavy-care resident
      population was positively related to expenditures prior to reimbursement reform,
      and it was negatively related to expenditures after the case-mix reimbursement
      policy was introduced. While facility-level changes in case mix had no reliable
      influence on costs or profits, nursing homes showing an increased prevalence of
      poor-quality nursing practices exhibited increases in efficiency and
      profitability. At the market level, reductions in excess or empty nursing home
      beds were accompanied by a significant growth in home health services. Moreover,
      nursing homes located in markets with expanding home health services exhibited
      higher increases in costs per case-mix unit. CONCLUSIONS: Characteristics of the
      reimbursement system appear to reward a cost minimization orientation with
      potentially detrimental effects on quality of care. These effects, exacerbated by
      a supply-constrained market, may be mitigated by policies that encourage the
      expansion of home health service availability.

PMID- 9776939
TI  - A longitudinal analysis of nursing home outcomes.
AB  - OBJECTIVE: To investigate resident and facility attributes associated with long
      term care health outcomes in nursing homes. DATA SOURCES: Quarterly Management
      Minutes Questionnaire (MMQ) survey data for Medicaid case-mix reimbursement of
      nursing homes in Massachusetts from 1991 to 1994, for specification of outcomes
      and resident attributes. Facility attributes are specified from cost report data.
      STUDY DESIGN: Multivariate logistic and "state-dependence" regression models are
      estimated for survival, ADL functional status, incontinence status, and mental
      status outcomes from longitudinal residence histories of Medicaid residents
      spanning 3 to 36 months in length. Outcomes are specified to be a function of
      resident demographic and diagnostic attributes and facility-level operating and
      nurse staffing attributes. PRINCIPAL FINDINGS: The estimated parameters for
      resident demographic and diagnostic attributes showed a great deal of construct
      validity with respect to clinical expectations regarding risk factors for adverse
      outcomes. Few facility attributes were associated with outcomes generally, and
      none was significantly associated with all four outcomes. CONCLUSIONS: The
      absence of uniform associations between facility attributes and the various long
      term care health outcomes studied suggests that strong facility performance on
      one health outcome may coexist with much weaker performance on other outcomes.
      This has implications for the aggregation of individual facility performance
      measures on multiple outcomes and the development of overall outcome performance
      measures.

PMID- 9776940
TI  - The demand for healthcare among racial/ethnic subpopulations.
AB  - OBJECTIVE: To analyze differences in the determination of healthcare expenditures
      among racial/ethnic groups. DATA SOURCE: The 1987 National Medical Expenditure
      Survey, a nationally representative sample of the United States population.
      (Nomenclature reflects racial/ethnic categories as used in the Survey.) STUDY
      DESIGN: The design was to estimate completely separate demand systems for blacks,
      Hispanics, and whites, perform statistical tests for the appropriateness of such
      separation, and carry out various simulations of healthcare expenditures. DATA
      COLLECTION/EXTRACTION METHODS: All black, white, and Hispanic persons in the 1987
      NMES Household Survey were used in this analysis. PRINCIPAL FINDINGS: Several of
      the differences among the equations for the three racial/ethnic groups appear to
      be related to access to care, particularly between Hispanics and whites, and to a
      lesser degree between blacks and whites. Simulations indicated that most of the
      differences in healthcare spending were due on net to differences in
      characteristics of the sampled persons and their environments. However, for
      Hispanics relative to both blacks and whites, some of the differences in total
      expenditures were also due to differences in the behavior embodied in the
      equations. CONCLUSIONS: It would be inadequate, and possibly misleading, to allow
      for differences in health expenditures by simply including dummy variables for
      blacks, Hispanics, and/or whites in pooled equations estimated for the entire
      sample. Studies that allow one to analyze the institutional and behavioral
      aspects of healthcare spending in greater detail are needed for a better
      understanding of these racial/ethnic differences.

PMID- 9776941
TI  - Too little time? The recognition and treatment of mental health problems in
      primary care.
AB  - OBJECTIVES: To assess the effect of practice characteristics on the diagnosis and
      treatment of mental health problems in primary care. DATA SOURCE: National
      Ambulatory Medical Care Survey (NAMCS) 1991-1994. STUDY DESIGN: We examine the
      effect of visit characteristics and practice characteristics on rates of
      diagnosis of mental health problems, rates of referral, and rates of use of
      psychotropic medications. We characterize each primary care physician's practice
      using information about the ways in which that physician treated patients who did
      not have mental health problems. PRINCIPAL FINDINGS: We find that median visit
      duration has a small, statistically insignificant effect on the rate of diagnosis
      and treatment of mental health problems. Physicians with large HMO caseloads are
      slightly more likely to diagnose mental health problems, but less likely to
      prescribe psychotropic medications, than are physicians who see few HMO patients.
      Practice style and specialty are important determinants of diagnosis and, to a
      lesser extent, of treatment. CONCLUSIONS: Physicians specialty and practice style
      are more strongly related to mental health diagnosis and treatment than are
      system characteristics such as visit duration and insurance composition.

PMID- 9776942
TI  - Empirically defined health states for depression from the SF-12.
AB  - OBJECTIVE: To define objectively and describe a set of clinically relevant health
      states that encompass the typical effects of depression on quality of life in an
      actual patient population. Our model was designed to facilitate the elicitation
      of patients' and the public's values (utilities) for outcomes of depression. DATA
      SOURCES: From the depression panel of the Medical Outcomes Study. Data include
      scores on the 12-Item Short Form Health Survey (SF-12) as well as independently
      obtained diagnoses of depression for 716 patients. Follow-up information, one
      year after baseline, was available for 166 of these patients. METHODOLOGY: We use
      k-means cluster analysis to group the patients according to appropriate
      dimensions of health derived from the SF-12 scores. Chi-squared and exact
      permutation tests are used to validate the health states thus obtained, by
      checking for baseline and longitudinal correlation of cluster membership and
      clinical diagnosis. PRINCIPAL FINDINGS: We find, on the basis of a combination of
      statistical and clinical criteria, that six states are optimal for summarizing
      the range of health experienced by depressed patients. Each state is described in
      terms of a subject who is typical in a sense that is articulated with our cluster
      analytic approach. In all of our models, the relationship between health state
      membership and clinical diagnosis is highly statistically significant. The models
      are also sensitive to changes in patients' clinical status over time.
      CONCLUSIONS: Cluster analysis is demonstrably a powerful methodology for forming
      clinically valid health states from health status data. The states produced are
      suitable for the experimental elicitation of preference and analyses of costs and
      utilities.

PMID- 9776944
TI  - Economies of scope and home healthcare.

PMID- 9776943
TI  - Hospitalizations for back and neck problems: a comparison between the Province of
      Ontario and Washington State.
AB  - OBJECTIVE: To examine back and neck hospitalizations in the Province of Ontario
      and Washington State. Because of their different organization and financing,
      there has been considerable interest in comparing healthcare systems in Canada
      and the United States. Features of healthcare systems might be expected to result
      in greater variations in care for elective than urgent conditions. DATA SOURCE:
      Automated hospital discharge databases. STUDY DESIGN: Previously developed
      algorithms were used to identify surgical and nonsurgical hospitalizations for
      back and neck problems in the administrative databases. We compared overall rates
      of hospitalization and lengths of hospital stay in Ontario and Washington as well
      as small area variations within the province and state. PRINCIPAL FINDINGS:
      Surgical back and neck hospitalizations were three times as common in Washington,
      but medical hospitalizations were twice as common in Ontario. Provincial lengths
      of stay were longer for both surgical and nonsurgical hospitalizations. Admission
      rates varied substantially and significantly among small areas in both Washington
      and Ontario. Variations in hospital length of stay were greater in Ontario,
      particularly for nonsurgical back and neck hospitalizations. CONCLUSION: The two
      jurisdictions had very different patterns of hospital utilization for one of the
      most common health problems seen by physicians. Our results suggest that the
      global controls on hospital budgets and access to technology in Ontario were
      associated with lower rates of surgery, higher rates of hospital-based medical
      care, and longer lengths of stay. They also indicate that the utilization review
      process in Washington was associated with lower small area variation rates for
      medical back care.

PMID- 9776945
TI  - Improving the quality of healthcare for children: implementing the results of the
      AHSR research agenda conference.
AB  - OBJECTIVE: To describe the rationale, development, content, and results of the
      AHSR-sponsored conference on developing a research agenda focused on improving
      the quality of care for children. DATA SOURCES AND METHODS: Planning documents,
      background papers, and conference proceedings. PRINCIPAL FINDINGS: The conference
      developed the research agenda focused on (1) monitoring the health of children;
      (2) evaluating the efficacy and effectiveness of health services for children;
      (3) assessing the quality of healthcare provided to children; (4) improving the
      quality of healthcare within health systems; (5) assessing the performance of
      community systems for children; (6) exploring the impact of different financial
      incentives on the provision of pediatric healthcare; and (7) developing and
      disseminating clinical practice guidelines and other information to physicians,
      families, and consumers. Specific issues and research questions in each area are
      also presented. Strategies for implementing the research agenda are presented and
      include: (1) expanding the child health services research workforce; (2)
      developing child healthcare quality improvement research centers; (3) conducting
      research in specific high-priority areas; (4) focusing research on improving the
      health of vulnerable populations; (5) improving child health data and collection
      systems at the national level; (6) developing better community health monitoring
      for children; (7) building and supporting research networks and a consortium of
      research users; and (8) developing a coordinated interagency federal effort to
      advance this agenda and to provide accountability for its completion. CONCLUSION:
      The proposed research agenda should be a national priority so that all Americans
      can be assured that children are receiving the best quality of care that the
      United States can provide.

PMID- 9776946
TI  - Overview of issues in improving quality of care for children.
AB  - OBJECTIVE: To provide a framework for a research agenda-setting conference on
      quality of care for children. DATA SOURCES/STUDY SETTING: Literature review.
      CONCLUSIONS: Research on quality of care for children has lagged behind its
      counterpart for adults. Defining key issues and questions in seven topic areas
      the health of children; the efficacy and effectiveness of health services for
      children; assessing quality of care; improving quality of care within health
      services delivery systems; assessing and improving quality at the community
      level; getting financial incentives right; and disseminating information about
      the results of research investigations-will facilitate the development of an
      effective research strategy. Ultimately, enhanced information in these areas will
      lead to improvements in the processes and outcomes of care for children.

PMID- 9776947
TI  - The health of children.
AB  - OBJECTIVE: To summarize the concept of child health and the measurement of child
      health status in order to help guide the evaluation of the effectiveness of
      medical, social, and policy programs. CONCLUSIONS: Opportunities for research on
      children's health status and quality of care abound. Comprehensive and functional
      definitions create problems of measurement, but investigators are making progress
      in measuring children's health status both generically and for specific chronic
      health conditions. RECOMMENDATIONS: Measures of child health need to be
      developed, improved, tested, and made user-friendly for clinical and policy
      research. The relationship between health status and a variety of social programs
      for children and families needs study. The impact of changes in healthcare
      organization and financing must be investigated, especially for children from
      vulnerable subgroups. Determining the value and effectiveness of preventive
      services is a pressing issue. It is crucial to understand better the link among
      quality of care; other factors biological, family, and social; and children's
      health status.

PMID- 9776948
TI  - Issues in studying the effectiveness of health services for children.
AB  - OBJECTIVES: To discuss issues in studying the effectiveness of health services
      for children, suggest areas in which more research is needed, and recommend
      strategies for future research. PRINCIPAL FINDINGS: Issues that should be
      considered include the choice of perspective, which will help determine the
      interventions studied and the measures of effectiveness and cost-effectiveness
      chosen. Unique challenges in this area include the fact that serious measurable
      morbidity is relatively uncommon in children, that causal relationships between
      services and outcomes may be difficult to establish, and that standard measures
      of cost-effectiveness may fail to accurately measure important benefits, such as
      reduced parental anxiety. More research is needed on high-risk and health
      promoting behaviors, on critical parent behaviors, on classifying children by
      vulnerability status, on modes of delivery of preventive care, and on violence
      prevention. RECOMMENDATIONS: Group-randomized designs and observational research
      designs that take advantage of natural variations in practice may be increasingly
      useful in effectiveness studies. Parent- and patient-reported measures of health
      status and quality of life should be made briefer and more practical for routine
      use, and better measures of cost-effectiveness are needed. Future research
      efforts can best be supported by the concerted efforts of various constituencies,
      including health plans, providers, patients, researchers, and the government.

PMID- 9776949
TI  - Assessing the quality of healthcare provided to children.
AB  - OBJECTIVE: To present a conceptual framework for evaluating quality of care for
      children and adolescents, summarize the key issues related to developing measures
      to assess pediatric quality of care, examine some existing measures, and present
      evidence about their current level of performance. PRINCIPAL FINDINGS: Assessing
      the quality of care for children poses many challenges not encountered when
      making these measurements in the adult population. Children and adolescents (from
      this point forward referred to collectively as children unless differentiation is
      necessary) differ from adults in two clinically important ways (Jameson and Wehr
      1993): (1) their normal developmental trajectory is characterized by change, and
      (2) they have differential morbidity. These factors contribute to the limitations
      encountered when developing measures to assess the quality of care for children.
      The movement of a child through the various stages of development makes it
      difficult to establish what constitutes a "normal" outcome and by extension what
      constitutes a poor outcome. Additionally, salient developmental outcomes that
      result from poor quality of care may not be observed for several years. This
      implies that poor outcomes may be observed when the child is receiving care from
      a delivery system other than the one that provided the low-quality care.
      Attributing the suboptimal outcome to the new delivery system would be
      inappropriate. Differential morbidity refers to the fact that the type,
      prevalence, and severity of illness experienced by children is measurably
      different from that observed in adults. Most children experience numerous self
      limited illness of mild severity. A minority of children suffer from markedly
      more severe diseases. Thus, condition-specific measures in children are
      problematic to implement for routine assessments because of the extremely low
      incidence and prevalence of most severe pediatric diseases (Halfon 1996).
      However, children with these conditions are potentially the segment of the
      pediatric population that can be most affected by variations in the quality of
      care. Improving the care provided to these children is likely to have the largest
      impact on quality of life and longevity. The low prevalence of most severe
      pediatric diseases also makes it difficult to evaluate the effectiveness of new
      treatment modalities; multi-center trials or long enrollment periods are usually
      required to obtain a large enough patient sample to conduct the necessary
      randomized controlled trials or cohort studies. Another challenge encountered
      when measuring quality of care for children is that, in most cases, they depend
      on adults to both obtain care and to report on the outcomes of that care. Parents
      and their children may have different perceptions of what defines health or have
      different levels of satisfaction with the care they receive. Children,
      particularly those with special needs, also depend on a broad range of services
      including the medical system, community intervention programs, social programs,
      and school-based services. Dependency on these various services adds to the
      difficulty of measuring and appropriately attributing health outcomes observed in
      children to a particular service delivery entity. Adolescents also depend on
      adults for access to some of their care; however, they have special needs related
      to confidentiality and parent-child information sharing. Adolescents commonly
      seek care at facilities, such as school-based clinics, that allow them to obtain
      confidential care. These facilities usually provide out-of-health plan care for
      these children, which raises special issues related to information availability
      for quality assessments and for assessing utilization patterns in this
      population. If the source of poor health outcomes is not known, quality
      improvement is not possible. The many challenges faced when constructing
      pediatric (this term will be used to refer to both children and adolescents)
      quality of care measures have resulted in few of these instruments being
      developed specifically for children. Most of the measures developed to date have
      either a very limited pediatric component or still require the process or outcome
      validation step. Although several practice guidelines and indicators of quality
      have been constructed, a conceptual framework to guide the development of such
      tools for quality assessment in the pediatric population is lacking. CONCLUSIONS:
      Pediatric health services researchers and the organizations that fund this work
      need to focus on developing a set of quality assessment tools that will address
      several challenging issues. Working within the context of the conceptual
      framework presented, we draw several conclusions related to issues that should be
      considered in developing quality of care measures for children.

PMID- 9776950
TI  - Improving the quality of care for children in health systems.
AB  - OBJECTIVE: To summarize the state of the art in quality improvement, review its
      application to care for children, and define the information that will be needed
      so that care for children can be further improved. PRINCIPAL FINDINGS: Health
      services for children exhibit numerous deficiencies in quality of care. The
      deficiencies cross all major domains of pediatric care--preventive services,
      acute care, and chronic care--and provide the opportunity for creative
      application of improvement strategies with a potential to benefit the health and
      well-being of children. Approaches to quality improvement have changed over the
      past two decades from those emphasizing the inspection of structural aspects of
      care and the imposition of sanctions to more dynamic strategies that emphasize
      measurement and comparison to motivate change; the use of evidence to specify
      aims for improvement; and the adoption of a variety of management strategies
      adapted from business and the social sciences to achieve these aims. These modern
      approaches to quality improvement have rarely been subjected to rigorous testing
      of their effectiveness. Moreover, their application in pediatrics has been less
      widespread than in adult healthcare. For children, several aspects about health
      services, such as the relative rarity of chronic illness, the important effects
      of social factors on health, and the limited cost, make some of these approaches
      even more challenging and may require new approaches or meaningful modifications.
      RECOMMENDATIONS: Research to understand better the general process of improvement
      will benefit improvement efforts for children. Research that builds the base of
      knowledge about best practices for children--effectiveness research--will also
      result in an enhanced capacity for improvement of those systems that care for
      children's health. Quality of care for children would be enhanced by targeted
      research examining ways both to foster improvement across segments of society,
      and to make recommendations for care more sensitive to children's development and
      environmental context. Research that supports incorporating the child's
      perspective into care is both uniquely challenging to perform and central to
      improving pediatric care.

PMID- 9776951
TI  - Assessing the performance of community systems for children.
AB  - OBJECTIVE: To present a framework for measuring the quality of community systems
      for children, based on key attributes of systems performance for children's
      services. We present a research agenda for refining the model, evaluating
      indicators across the performance domains identified, developing normative
      standards for performance, and assessing the empirical basis for performance
      criteria. PRINCIPAL FINDINGS: Systems performance can be measured. A systems
      approach to evaluating community systems for children needs to incorporate the
      multilevel service delivery networks, programs, and systems of care for children.
      A model of community systems performance for children includes key dimensions of
      structure, financing, and accountability. Attributes within these dimensions
      serve as indicators that communities can use to evaluate systems quality.
      Performance standards can be based on the evidence from field demonstrations as
      well as from normative assessments. RECOMMENDATIONS: The model of community
      systems performance should be refined and developed using empirical findings of
      analyses of children's systems. A set of indicators that capture vital aspects of
      performance and that are relevant, scientifically valid, and feasible should be
      developed and tested in field studies. Once indicators are evaluated for use in
      performance monitoring, communities will be able to implement performance
      monitoring.

PMID- 9776952
TI  - Getting the incentives right for children.
AB  - OBJECTIVE: One way to improve the functioning of the American child healthcare
      system is through the design of incentives. Objective: to examine what we know
      and need to know about designing incentives to encourage the production of high
      quality care both for healthy children and for children with serious illnesses.
      SUMMARY AND CONCLUSIONS: For healthy children, incentives should encourage the
      provision of preventive services, including services that encourage healthy
      behavior. For children with serious illnesses, incentives should reduce risk
      selection, promote collaborative systems of care, and ensure access to
      appropriate specialty services. Research findings needed for incentive design
      includes information on the actual working of existing incentive mechanisms as
      well as information about risk adjustment, mixed payment system, carve-outs, and
      other mechanisms to reduce risk selection; options for defining service scope
      that encourage collaboration; and information about the ways in which quality
      measurement interacts with payment incentives.

PMID- 9776953
TI  - Specific issues related to developing, disseminating, and implementing pediatric
      practice guidelines for physicians, patients, families, and other stakeholders.
AB  - OBJECTIVE: To describe ways in which medical information should be developed and
      disseminated, focusing on pediatric practice guidelines as an example of one type
      of information. PRINCIPAL FINDINGS: The methodology of guideline development is
      well known and has been previously reviewed. Guideline development poses problems
      for many medical specialties, but particularly for pediatrics, because (1) few
      diseases are prevalent, (2) only limited randomized controlled trials have been
      conducted with respect to specific diagnostic and therapeutic options, and (3)
      clinicians often are dealing with patient surrogates--parents--rather than with
      the actual patient. Patient and family involvement in guideline development and
      dissemination has been limited and may affect the likelihood that guidelines will
      be adopted and subsequently improve child health outcomes. The science of
      dissemination, including guidelines and other information, is poorly developed.
      Little is known about the most effective ways to ensure that guidelines reach
      clinicians and are adopted. Finally, the effect of guidelines on child health
      outcomes is itself uncertain. RECOMMENDATIONS: (1) Research efforts should focus
      on guideline dissemination and adoption. (2) The effect of guideline
      implementation on health outcomes needs to be better understood. (3) Parents
      should be more involved in guideline dissemination and adoption.

PMID- 9776954
TI  - Chronic pulmonary hypertension--the monocrotaline model and involvement of the
      hemostatic system.
AB  - Monocrotaline (MCT) is a toxic pyrrolizidine alkaloid of plant origin.
      Administration of small doses of MCT or its active metabolite, monocrotaline
      pyrrole (MCTP), to rats causes delayed and progressive lung injury characterized
      by pulmonary vascular remodeling, pulmonary hypertension, and compensatory right
      heart hypertrophy. The lesions induced by MCT(P) administration in rats are
      similar to those observed in certain chronic pulmonary vascular diseases of
      people. This review begins with a synopsis of the hemostatic system, emphasizing
      the role of endothelium since endothelial cell dysfunction likely underlies the
      pathogenesis of MCT(P)-induced pneumotoxicity. MCT toxicology is discussed,
      focusing on morphologic, pulmonary mechanical, hemodynamic, and biochemical and
      molecular alterations that occur after toxicant exposure. Fibrin and platelet
      thrombosis of the pulmonary microvasculature occurs after administration of
      MCT(P) to rats, and several investigators have hypothesized that thrombi
      contribute to the lung injury and pulmonary hypertension. The evidence for
      involvement of the various components of the hemostatic system in MCT(P)-induced
      vascular injury and remodeling is reviewed. Current evidence is consistent with
      involvement of platelets and an altered fibrinolytic system, yet much remains to
      be learned about specific events and signals in the vascular pathogenesis.

PMID- 9776955
TI  - An overview of recent studies on the potential of pulp-mill effluents to alter
      reproductive parameters in fish.
AB  - In the early 1990s, many Canadian pulp and paper mills implemented process
      changes to comply with new regulations that came into effect in 1993. These
      regulations placed stricter guidelines on a number of parameters in effluent
      discharges, including limits on acute toxicity, on the discharges of suspended
      solids, and on biochemical oxygen demand. To meet these new regulations, many of
      the older Canadian pulp and paper mills had to install secondary treatment
      systems. The investment by the Canadian pulp and paper industry was in excess of
      $5 billion, and the implementation of the new regulations and the process changes
      took several years. The new regulations were an extension of regulations designed
      in the early 1970s and were not designed specifically to address the reproductive
      responses recently reported in fish collected downstream of mills in Scandinavia
      and North America. This report describes a series of projects conducted between
      1991 and 1996 to evaluate the effectiveness of the new regulations to address the
      issue of reproductive responses in fish associated with exposure to pulp-mill
      effluents. These studies have shown that the existing short-term bioassays do not
      adequately predict the potential of effluents to affect reproduction in wild
      fish. Laboratory testing using fathead minnows exposed over a full life cycle
      confirmed depression in sex steroid production, delay in sexual maturity, reduced
      egg production, and changes in secondary sex characteristics documented at some
      sites. Our studies demonstrated that both steroid hormone changes and induction
      of liver detoxification enzymes take place quickly. While short-term exposures
      can predict the potential of some effluents to impact steroid hormone production,
      there is no readily available assay that can be widely applied. In the absence of
      a usable and transferable laboratory bioassay, field collections were conducted
      at a number of sites. Generalizations are not possible at this time, but impacts
      have been seen at a variety of sites, and partial recovery has been documented at
      five sites in North America following various process and waste treatment
      changes. Data gaps and critical research areas are identified.

PMID- 9776956
TI  - Do poison centers save money...? What are the data?

PMID- 9776957
TI  - The pharmacokinetics of continuous infusion pralidoxime in children with
      organophosphate poisoning.
AB  - OBJECTIVE: To define the pharmacokinetics of continuous infusion pralidoxime in
      organophosphate-poisoned children. STUDY DESIGN: Open-label study in 11 children
      and adolescents poisoned with organophosphates or carbamates. Serial blood
      samples were obtained during continuous pralidoxime infusion and after the drug
      was stopped. RESULTS: Patients were treated for 12-43 hours. Steady-state
      concentrations were (mean +/- SD) 22.2 +/- 12.3 mg/L. Volume of distribution
      ranged from 1.7 to 13.8 L/kg and was significantly higher in the more severely
      poisoned subjects. Elimination half-life was 3.6 +/- 0.8 hours, and clearance was
      0.88 +/- 0.55 L/h/kg. After initiation of continuous infusion pralidoxime, only 1
      patient required any additional atropine to control recurrent muscarinic
      symptoms. All patients exhibited complete clinical recovery. CONCLUSIONS: The
      pharmacokinetics of pralidoxime in poisoned children following continuous
      intravenous infusion are widely variable and differ from those previously
      reported in both healthy and poisoned adults. A loading dose of 25-50 mg/kg is
      recommended followed by a continuous infusion of 10-20 mg/kg/h. A loading dose of
      50 mg/kg may be appropriate in more severely poisoned patients.

PMID- 9776958
TI  - Respiratory tract inflammation in swine confinement workers studied using induced
      sputum and exhaled nitric oxide.
AB  - OBJECTIVE: To further define the asthma-like syndrome seen in swine confinement
      workers. DESIGN: A cross-sectional study was performed at a swine confinement
      facility in rural Nebraska and at the University of Nebraska Medical Center,
      Omaha, Nebraska. PARTICIPANTS: 24 swine confinement workers and 14 urban normal
      control subjects. All subjects completed a questionnaire concerning respiratory
      complaints. We performed hypertonic saline challenges on the swine confinement
      workers and control subjects in order to induce expectoration of sputum. Cell
      counts and cell differentials were determined in the induced sputum samples.
      Nasal, mean, and peak exhaled nitric oxide was measured in both groups.
      Spirometry was also done. RESULTS: Swine confinement workers were significantly
      more likely to report wheezing, cough, and sinusitis symptoms than controls (p =
      .003). Macrophages were significantly elevated in the induced sputum samples of
      the swine confinement workers vs the control subjects (0.59 macrophages/mL +/-
      0.1 SEM vs 0.36 +/- .16; p = .006), while there was no difference in numbers of
      neutrophils. No eosinophils were observed. A small elevation in mean exhaled
      nitric oxide was seen in the swine confinement workers compared to normal
      controls (11.7 ppb +/- 0.6 SEM vs 10.2 +/- 1.6; p = 0.023). Spirometry values did
      not differ statistically between swine confinement workers and the control group.
      CONCLUSIONS: Swine confinement workers have signs and symptoms of lower
      respiratory tract inflammation when studied using induced sputum and exhaled
      nitric oxide. Findings in the swine confinement workers differ from those in
      asthmatics and chronic bronchitis.

PMID- 9776959
TI  - Personal decontamination after exposure to stimulated liquid phase contaminants:
      functional assessment of a new unit.
AB  - OBJECTIVE: To evaluate the efficacy of a decontamination station following
      exposure of volunteers to liquids with physical characteristics comparable to
      sarin and mustard gas. DESIGN: Twenty-four volunteers participated in the
      experiment which was performed with all staff wearing personal protective
      equipment including respiratory protection. The clothes, skin, and hair of the
      volunteers were contaminated with the simulated liquid phase contaminants, ethyl
      lactate and methyl salicylate. Sulphur hexafluoride gas was used to confirm the
      ventilation efficacy. Decontamination followed guidelines using a two-stage
      procedure. In the first chamber, all volunteers received a 3-minute shower with
      water at 30 degrees C, and their clothes but not their respiratory masks were
      removed. In the second, they were twice washed thoroughly with soap and water.
      After decontamination, the volunteers entered a third chamber for first aid
      measures. RESULTS: The air concentration of sulphur hexafluoride was reduced by
      1:10,000 between the first and the third chambers. Ethyl lactate and methyl
      salicylate were measured in low concentrations in the third chamber. The capacity
      was 16 volunteers per hour with two-thirds on stretchers. After self
      decontamination of the staff, the concentration of ethyl lactate increased
      significantly in the third chamber, consistent with residual ethyl lactate
      adsorbed by their underwear. This observation revealed a deficiency in the
      guidelines for self-decontamination. CONCLUSION: The capacity of the
      decontamination unit was found to be 16 volunteers per hour. The ventilation
      system and guidelines of the decontamination unit were demonstrated to be
      effective under the conditions examined. The self-decontamination of the staff
      was not optimal.

PMID- 9776961
TI  - Nitric oxide inhalation for paraquat--surviving both poisoning and therapy?

PMID- 9776960
TI  - Nitric oxide inhalation for paraquat-induced lung injury.
AB  - BACKGROUND: When ingested, concentrated paraquat can cause either rapid death
      from multisystem failure and cardiovascular shock or delayed death from
      progressive pulmonary fibrosis. Diquat ingestion does not usually cause pulmonary
      fibrosis, but produces early onset acute renal failure. CASE REPORT: A 52-year
      old male ingested approximately 50 mL of a solution containing 13% paraquat and
      7% diquat (about 6650 mg of paraquat and 3500 mg of diquat), and subsequently
      developed adult respiratory distress syndrome and pulmonary fibrosis. Survival
      prediction employing the criteria of Hart et al. for paraquat plasma levels was
      30%. From the probable amount of paraquat ingested, severe toxicity was expected.
      The clinical course was not consistent with significant diquat toxicity.
      Treatment included oral Fuller's earth, forced diuresis, hemofiltration, N
      acetylcysteine, methylprednisolone, cyclophosphamide, vitamin E, colchicine, and
      delayed continuous nitric oxide inhalation. The patient recovered and pulmonary
      function was subsequently normal. CONCLUSION: It is unclear which, if any, of the
      above treatments contributed to recovery, but the encouraging outcome suggests a
      possible benefit of nitric oxide inhalation in paraquat poisoning which deserves
      further study.

PMID- 9776962
TI  - Severe respiratory distress following sodium oleate ingestion.
AB  - CASE REPORT: Oleic acid and oleate are pulmonary toxins used to create laboratory
      models of acute respiratory distress syndrome, but there is little information on
      human toxicity. We report the intentional ingestion of 50 mL sodium oleate 20% by
      a 22-year-old woman with no symptoms for the first 2 days after ingestion. Her
      respiratory status deteriorated rapidly on day 3 progressing to acute respiratory
      distress syndrome (PaO2/FIO2 < 100 mm Hg) on day 4. Treatment with high-dose
      steroids and intensive respiratory support including high-frequency jet
      ventilation were associated with gradual but complete recovery by day 39. The
      delayed onset of symptoms suggested that the lung injury was due to the systemic
      circulation of oleate to the lungs rather than to direct aspiration. In oral
      poisoning by sodium oleate, the lung is the first and most lethally affected
      target organ in humans. This case demonstrates that ingestion of a relatively
      small amount of sodium oleate can cause delayed, progressively severe, lung
      injury.

PMID- 9776963
TI  - Aspiration of black mustard.
AB  - CASE REPORT: A 15-month-old healthy boy presented in acute, severe respiratory
      distress after ingesting and aspirating ground black mustard (Brassicu nigra)
      seeds. Ground mustard seeds contain the toxic compound, isothiocyanate, that
      causes airway irritation and edema similar to black pepper (known to be lethal
      with aspiration). This case documents the potential toxicity of black mustard
      which has not been previously reported.

PMID- 9776964
TI  - ECG conduction delays associated with massive bupropion overdose.
AB  - BACKGROUND: Bupropion, a relatively new antidepressant, is highly regarded for
      its safety profile in therapeutic doses and in the overdose. Seizure is the
      primary adverse reaction associated with bupropion overdoses. Clinically
      significant cardiovascular complications are rare. CASE REPORT: We report the
      case of an adult male who ingested 9 g bupropion and developed neurologic
      toxicity as well as intraventricular conduction disturbances on
      electrocardiogram. Cardiac monitoring of these patients should be considered.

PMID- 9776965
TI  - Loss of consciousness from acute quetiapine overdosage.
AB  - BACKGROUND: Quetiapine (Seroquel) is a new atypical antipsychotic agent developed
      for the treatment of schizophrenia. This dibenzothiazepine derivative possesses
      high affinity for 5-HT2 receptors with lower affinity for D1 and D2 dopamine
      receptors. In comparison to other antipsychotic agents, quetiapine has less
      antimuscarinic and alpha1 antagonist receptor activity. Overdose reports outside
      of clinical trials are limited. We report an intentional overdose of quetiapine
      by a schizophrenic. CASE REPORT: A 26-year-old female presented to the emergency
      department following an alleged ingestion of greater than 10,000 mg of
      quetiapine. At 1 1/2 hours postingestion, the patient was awake, ambulatory, and
      responded to verbal stimuli. At 2 1/2 hours postingestion, the patient
      experienced a decreased level of consciousness and responded only to deep pain.
      Physical findings included sinus tachycardia, pupils 3-4 mm and sluggish, and BP
      135/70. Within 16 hours, the patient became awake and alert and was subsequently
      extubated. Serum electrolytes and blood count were unremarkable. The
      electrocardiogram at 18 hours postingestion showed a sinus tachycardia, which
      lasted for approximately 40 hours postingestion. A follow-up electrocardiogram at
      42 hours postingestion was normal. CONCLUSION: This ingestion resulted in the
      loss of consciousness with need for airway protection and persistent tachycardia.
      Major overdoses of quetiapine warrant close observation in an intensive care
      setting.

PMID- 9776966
TI  - Optic neuritis with residual tunnel vision in perchloroethylene toxicity.
AB  - CASE REPORT: In a 57-year-old female owner of a dry-cleaning shop, we describe
      the association of severe bilateral optic neuritis with unexpectedly high
      concentrations of perchloroethylene/metabolites in the blood and of chloroform in
      urine. Visual disturbances consisted of complete blindness for 9 days in the left
      eye, for 11 days in the right eye, with bright phosphenes and pain on eye
      rotation. Only central (2-3 degrees radius) vision recovered in the following
      months. CONCLUSION: Although environmental concentrations of perchloroethylene
      were within normal limits, we measured five-fold increases in vapors emitted when
      ironing freshly dry-cleaned fabrics, and suggest that inhalation of
      perchloroethylene vapors was the cause of this case of ocular nerve toxicity,
      recapitulating a previous report of major perchloroethylene toxicity.

PMID- 9776967
TI  - Carisoprodol-induced myoclonic encephalopathy.
AB  - CASE REPORT: A 39-year-old man ingested 35 g carisoprodol. He developed
      agitation, tachycardia, myoclonus, and coma. The blood carisoprodol was 71
      micrograms/mL; the meprobamate was 26 micrograms/mL. DISCUSSION: Carisoprodol
      overdose is thought to induce simple central nervous system depression. This case
      demonstrates a severe overdose with symptoms more consistent with myoclonic
      encephalopathy. A review of cases presenting to the San Francisco Division of the
      California Poison Control System during 1997 suggests that carisoprodol is more
      commonly associated with agitation and bizarre movement disorders than the
      current literature suggests. The pharmacology and potential mechanisms of
      toxicity are discussed. CONCLUSION: Agitation, hypertonia, and a myoclonic
      encephalopathy may be seen with significant carisoprodol intoxication.

PMID- 9776968
TI  - Prolonged formation of methemoglobin following nitroethane ingestion.
AB  - BACKGROUND: Artificial nail removers containing nitroethane pose a serious risk
      of toxicity when ingested. CASE REPORTS: We report 3 cases of children under 3
      years of age who developed prolonged methemoglobinemia following ingestions of
      small quantities of these nitroethane-containing products. Methylene blue therapy
      reduced the methemoglobin level in all 3 children; however, in 2 of these
      children methemoglobin levels increased again several hours later and required
      additional methylene blue. Accurate substance identification is essential for
      appropriate management of ingestions of fingernail products. The availability of
      nitroethane products for home use should be questioned.

PMID- 9776969
TI  - Love potions and the ointment of witches: historical aspects of the nightshade
      alkaloids.
AB  - BACKGROUND: Nightshade plants (Solanaceae) have been utilized as hallucinogenic
      drugs since antiquity in nearly every culture. The Solanaceae alkaloids, atropine
      and scopolamine, were the active substances in ointment of witches and medieval
      anesthetics, and in modern poisons. They are still currently used as
      hallucinogenic drugs. In poisonings, a dosage- and substance-dependent clinical
      picture occurs, with central and peripheral symptoms. Hallucinations are
      predominant in the middle dose range, which explains the drugs' earlier
      utilization for religious and prophetic purposes. Respiratory depression and
      arrest at high doses confirm the use of scopolamine as a lethal poison. Despite
      this, the nightshade alkaloids were utilized in clinical medicine in the 19th
      century. This is an overview of the cultural history of the nightshade alkaloids.

PMID- 9776970
TI  - Stachybotrys revisited.

PMID- 9776971
TI  - Stachybotrys: still under investigation.

PMID- 9776972
TI  - Identification of unknown mushrooms: the good, the bad, and the ugly.

PMID- 9776973
TI  - Identification of unknown mushrooms: if it ain't broke, don't fix it.

PMID- 9776974
TI  - The mortality rate of salicylate poisoning.

PMID- 9776975
TI  - Improving patient care by reporting problems with medical devices.

PMID- 9776976
TI  - The MedWatch program.

PMID- 9776977
TI  - Mutation measurement in mammalian cells. IV: Comparison of gamma-ray and chemical
      mutagenesis.
AB  - The interaction of chemical mutagens with mammalian cells is much more complex
      than that of gamma-irradiation because of the different ways in which chemical
      agents react with cell and medium components. Nevertheless, the system previously
      described for analysis of mutagenesis by gamma-radiation appears applicable to
      chemical mutagenesis. The approach involves measurement of cell survival, use of
      caffeine to inhibit repair, analysis of mitotic index changes, and quantitation
      of microscopically visible structural changes in mitotic chromosomes. The
      behavior of a variety of chemical mutagens and nonmutagens in this system is
      described and compared with that of gamma-irradiation. The procedure is simple
      and the results reasonably quantitative though less so than those of gamma
      irradiation. The procedure can be used for environmental monitoring, analysis of
      mutational events, and individual and epidemiological testing. Mutational events
      should be classified as primary or secondary depending on whether they represent
      initial genomic insult, or genomic changes resulting from primary mutation
      followed by structural changes due to metabolic actions. While caffeine has
      multiple effects on the mammalian genome, when used under the conditions
      specified here it appears to act principally as an inhibitor of mutation repair,
      and so affords a measure of the role of repair in the action of different
      mutagens on cells in the G2 phase of the life cycle.

PMID- 9776978
TI  - A panel of partial chromosome paints and YAC probes specific for human chromosome
      2.
AB  - Twenty nine hybrids retaining fragments of human chromosome 2 were characterized
      by reverse-FISH and by a panel of 106 STSs. Most of the hybrids are radiation
      hybrids retaining fragments of chromosome 2 as the only human contribution. The
      hybrid panel dissected chromosome 2 in 69 distinct physical regions, allowing a
      fine mapping of the sequences. These hybrids are particularly useful as starting
      points for generation, via Alu-PCR, of specific partial chromosome paints (PCP).
      We also report the mapping by FISH of 60 YACs located on chromosome 2. These
      resources can be advantageously used in cytogenetic investigations, with
      particular reference to cancer cytogenetics, as illustrated with the renal
      carcinoma cell line KRC/Y.

PMID- 9776979
TI  - Cloning and characterization of the promoter of baboon XRCC1, a gene involved in
      DNA strand-break repair.
AB  - The DNA repair gene XRCC1 was the first cloned human DNA repair gene involved in
      resistance to ionizing radiation. Previous studies have shown that rodent and
      baboon homologs of XRCC1 are expressed in all tested tissues with significantly
      higher levels in testis. Furthermore, expression of murine XRCC1 is most abundant
      in pachytene spermatocytes and round spermatids. To begin to study regulation of
      XRCC1 expression, the 5' region of baboon XRCC1 was cloned and characterized. 400
      bp of 5'-flanking region showed the greatest promoter activity, while -194 to -8
      bp of the 5'-flanking region displayed core promoter activity in transient
      transfection assays. A comparison between baboon and human 5'-flanking sequences
      in the core promoter region revealed a potential CAAT-box, an imperfect CREB
      binding site and two putative Sp1-binding sites. Results from transient
      transfection assays in which each putative binding site was individually mutated,
      indicated that the distal Sp1-binding site has a functional role in
      transcription. In comparison, both putative Sp1-binding sites bound protein(s)
      from HeLa cell nuclear extracts in vitro. In vitro binding was lost when mutated
      Sp1 sites were used in gel mobility shift assays. Finally, anti-Sp1 antibodies
      produced mobility supershifts, thereby indicating Sp1 or an Sp1-like protein
      bound to the DNA fragment in vitro.

PMID- 9776981
TI  - Construction and characterization of single-transcript tricistronic retroviral
      vectors using two internal ribosome entry sites.
AB  - We describe a series of retroviral vectors containing two internal ribosome entry
      sites (IRES) for the co-transcription of three genes. Transcription of the single
      transcript tricistronic mRNA is under the control of a Harvey murine sarcoma
      virus long terminal repeat. The 5'-most open reading frame is under either cap
      dependent or cap-independent translational control, while the two downstream open
      reading frames are translated in a cap-independent fashion using the initiation
      codons of their respective IRES elements. Both IRES elements are taken from the
      encephalomyocarditis virus. To characterize these vectors, we used the human
      multidrug resistance gene (MDR1) in the 5' position, the gene for green
      fluorescent protein (GFP) in the middle position, and neo in the 3' position. The
      vectors were either transfected directly into NIH3T3 mouse fibroblasts or
      packaged into retrovirus and then transduced into NIH3T3 cells. Gene transfer was
      followed by selection with colchicine, which selects for expression of the MDR1
      gene, or with G418, which selects for expression of the neo gene. Thus, we could
      determine the function of the tricistronic vectors under conditions of selection
      for either the 5'-most or the 3'-most gene. In DNA-mediated transfections, we
      were able to achieve expression of all three open reading frames under either
      selection condition. We obtained higher expression of all three genes when
      colchicine was used to select for MDR1 expression than when G418 was used to
      select for neo expression. Expression of the non-selected GFP gene (the middle
      cistron) was unstable, most likely due to loss of integrated GFP DNA sequences
      during long-term culturing. We were able to achieve retrovirus-mediated
      transduction of all three genes, but this was an inefficient process.

PMID- 9776982
TI  - Localization of PiUS, a stimulator of cellular phosphate uptake to human
      chromosome 3p21.3.
AB  - A novel gene, PiUS, was recently cloned and shown to increase phosphate uptake
      when expressed in oocytes, indicating that it may be an important regulator of
      cellular phosphate homeostasis. The phosphate wasting disease autosomal dominant
      hypophosphatemic rickets (ADHR) was previously mapped to chromosome 12p13 by
      linkage analysis. PiUS' role as a modulator of phosphate transport, as well as
      its intestinal and renal expression made the gene an appropriate candidate for
      ADHR. The purpose of our study was to determine the chromosomal localization of
      the human PiUS gene through the use of somatic cell hybrids and radiation hybrid
      mapping. In the present work, PiUS was localized to human chromosome 3p21.3 and
      is therefore not the ADHR gene.

PMID- 9776984
TI  - Earnings and feminization of the veterinary profession.

PMID- 9776983
TI  - Is xenotransplantation worth the risk?

PMID- 9776980
TI  - Recombination hotspot activity of hypervariable minisatellite DNA requires
      minisatellite DNA binding proteins.
AB  - Hypervariable minisatellite DNA repeats are found at tens of thousands of loci in
      the mammalian genome. These sequences stimulate homologous recombination in
      mammalian cells [Cell 60:95-103]. To test the hypothesis that protein-DNA
      interaction is required for hotspot function in vivo, we determined whether a
      second protein binding nearby could abolish hotspot activity. Intermolecular
      recombination between pairs of plasmid substrates was measured in the presence or
      absence of the cis-acting recombination hotspot and in the presence or absence of
      the second trans-acting DNA binding protein. Minisatellite DNA had hotspot
      activity in two cell lines, but lacked hotspot activity in two closely related
      cell lines expressing a site-specific helicase that bound to DNA adjacent to the
      hotspot. Suppression of hotspot function occurred for both replicating and non
      replicating recombination substrates. These results indicate that hotspot
      activity in vivo requires site occupancy by minisatellite DNA binding proteins.

PMID- 9776985
TI  - Comments on tenectomy and onychectomy in cats.

PMID- 9776986
TI  - Injection-site sarcomas in cats.

PMID- 9776987
TI  - Vaccine injection-site sarcoma in a ferret.

PMID- 9776988
TI  - Education and empowerment may improve client compliance.

PMID- 9776989
TI  - What is your diagnosis? Bone cyst causing acute lameness in a dog.

PMID- 9776991
TI  - Primer on estimating withdrawal times after extralabel drug use.

PMID- 9776990
TI  - Anesthesia case of the month. Pacemaker malfunction during anesthesia in a dog.

PMID- 9776992
TI  - Noncompartmental methods of drug characterization: statistical moment theory.

PMID- 9776993
TI  - Randomized controlled trial of doxorubicin versus dactinomycin in a multiagent
      protocol for treatment of dogs with malignant lymphoma.
AB  - OBJECTIVE: To compare efficacy and toxicity of 2 multiagent chemotherapeutic
      protocols similar in all respects except that 1 incorporated dactinomycin and the
      other incorporated doxorubicin for treatment of dogs with malignant lymphoma.
      DESIGN: Randomized controlled trial. ANIMALS: 45 dogs with malignant lymphoma.
      PROCEDURE: Dogs were randomly assigned to a doxorubicin or dactinomycin treatment
      group. Time to first remission, duration of first remission, survival time, and
      prevalence of toxicoses, particularly number of episodes of dose-limiting
      neutropenia and gastrointestinal toxicoses, were compared between groups.
      RESULTS: 37 dogs received at least 1 dose of doxorubicin (21 dogs) or
      dactinomycin (16). Median time to first remission was not significantly different
      between groups, but median duration of first remission and median survival time
      were significantly longer for dogs in the doxorubicin treatment group than for
      dogs in the dactinomycin treatment group. Number of dogs that died, number of
      episodes of dose-limiting neutropenia, and number of episodes of gastrointestinal
      toxicoses were not significantly different between groups. CLINICAL IMPLICATIONS:
      A multiagent chemotherapeutic protocol incorporating doxorubicin was
      significantly more effective in dogs with malignant lymphoma than a similar
      protocol incorporating dactinomycin. Despite the lower cost and lack of
      cardiotoxicity, dactinomycin is not an equivalent substitute for doxorubicin in
      the initial treatment of dogs with malignant lymphoma.

PMID- 9776994
TI  - Recombinant human granulocyte colony-stimulating factor for treatment of puppies
      with neutropenia secondary to canine parvovirus infection.
AB  - OBJECTIVE: To determine the effect of treatment with recombinant human
      granulocyte colony-stimulating factor (rhG-CSF) for puppies with neutropenia
      secondary to canine parvovirus infection. DESIGN: Randomized controlled clinical
      trial. ANIMALS: 23 puppies. PROCEDURE: Diagnosis was confirmed by use of an ELISA
      for detection of canine parvovirus antigen in feces, and all puppies received
      standard treatment for parvoviral enteritis. All puppies had neutropenia (< 1,000
      neutrophils/microliter) at the time of admission to the hospital or within 4 days
      afterward. Eleven puppies were treated with rhG-CSF daily until neutrophil count
      was > 1,500 cells/microliter; the remaining 12 puppies were not treated with rhG
      CSF. RESULTS: We did not detect any significant differences between groups
      regarding duration of hospitalization, neutrophil count when neutropenia was
      first detected, lowest neutrophil count, or time until neutrophil count was >
      1,500 cells/microliter. CLINICAL IMPLICATIONS: Results suggest that treatment
      with rhG-CSF may not be beneficial in puppies with neutropenia secondary to
      canine parvovirus infection.

PMID- 9776996
TI  - Agreement between two methods for measuring urine pH in cats and dogs.
AB  - OBJECTIVE: To compare urine pH of cats and dogs determined by use of a dipstrip
      and a pH meter. DESIGN: Prospective study. SAMPLE POPULATION: 109 urine samples
      from 88 cats that were clinically normal or had signs of irritative urination, 52
      samples from 13 clinically normal dogs, and 3 samples from 3 dogs with urinary
      tract infections. PROCEDURE: Measurements of urine pH were obtained by use of a
      dipstrip and pH meter, and degree of agreement between measurements was
      evaluated. RESULTS: Mean difference (+/- 2 SD) between the 2 methods was 0.1 +/-
      0.9 pH units. Only 65 of 164 (40%) samples measured by use of a dipstrip were
      within 0.25 pH units of results obtained by use of the pH meter. CLINICAL
      IMPLICATIONS: When an accurate measurement of urine pH is critical for clinical
      decision making, the measurement should be made by use of a pH meter. Dipstrips
      typically are not accurate enough to be clinically useful.

PMID- 9776995
TI  - Efficacy of oral administration of itraconazole to cats with dermatophytosis
      caused by Microsporum canis.
AB  - OBJECTIVE: To determine efficacy of orally administered itraconazole in cats with
      dermatophytosis caused by Microsporum canis. DESIGN: Uncontrolled clinical trial.
      ANIMALS: 15 cats with dermatophytosis caused by M canis. PROCEDURE: All cats were
      treated with itraconazole (1.5 to 3.0 mg/kg [0.7 to 1.4 mg/lb] of body weight,
      PO, q 24 h, for 15 days). Six cats had been treated with griseofulvin (10 mg/kg
      [4.5 mg/lb], PO, q 24 h) during a 60-day period, but their clinical condition had
      not improved. Five cats treated at the highest dosage of itraconazole vomited or
      became anorectic. Consequently, dosages were progressively decreased for each cat
      until adverse effects were not evident. After treatment, samples of hair were
      submitted for fungal cultures, and if appropriate, treatment was repeated when
      culture results were positive. RESULTS: 8 cats treated with itraconazole
      recovered completely, as indicated by resolution of lesions and negative results
      of fungal cultures. Six of these 8 cats received a single 15-day course of
      treatment, whereas the remaining 2 cats needed prolonged treatment (two 15-day
      courses of treatment and three 15-day courses of treatment). In 4 other cats that
      became clinically normal, M canis was isolated from hair samples obtained at the
      completion of treatment, even though only 1 colony or a small number of colonies
      was isolated. In the other 3 cats, itraconazole did not cause clinical
      improvement, and culture results remained positive. CLINICAL IMPLICATIONS: Oral
      administration of itraconazole at dosages of 1.5 to 3.0 mg/kg may be useful for
      the treatment of cats with dermatophytosis attributable to M canis infections.

PMID- 9776997
TI  - Use of human recombinant erythropoietin and prednisone for treatment of
      myelodysplastic syndrome with erythroid predominance in a dog.
AB  - A 7-year-old German Shepherd dog was referred for evaluation of severe
      nonregenerative anemia (PCV, 10%; reticulocyte fraction, 0.2%). Cytologic
      examination of a bone marrow aspirate indicated erythroid predominance and
      dyserythropoiesis, and a diagnosis of myelodysplastic syndrome (MDS) with
      erythroid predominance was made. The dog was given a single blood transfusion and
      was treated with prednisone and recombinant human erythropoietin (EPO). Eight
      weeks later, anemia had resolved. The dog remained clinically normal 30 months
      after treatment, with a PCV of 45%. Results suggest that EPO may be useful in the
      treatment of dogs with MDS with erythroid predominance or erythroleukemia.
      Additional studies are required to confirm the benefit of EPO to manage MDS
      associated anemia in dogs.

PMID- 9776998
TI  - Prognostic importance of alkaline phosphatase activity in serum from dogs with
      appendicular osteosarcoma: 75 cases (1990-1996).
AB  - OBJECTIVE: To determine whether alkaline phosphatase activity in dogs with
      appendicular osteosarcoma can be used as a prognostic indicator. DESIGN:
      Retrospective study. ANIMALS: 75 dogs with appendicular osteosarcoma. PROCEDURE:
      Serum total alkaline phosphatase (TALP) and bone-specific alkaline phosphatase
      (BALP) activities were determined from archival serum samples obtained at various
      times during treatment of appendicular osteosarcoma and follow-up evaluations.
      Associations among activities of TALP and BALP and survival and disease-free
      intervals, percentage of bone length involved with tumor, histologic subtype, and
      method of surgical treatment were evaluated. RESULTS: High activities of TALP and
      BALP before surgery were significantly associated with shorter survival and
      disease-free intervals in dogs undergoing surgery (amputation or limb-sparing
      procedure) and adjuvant chemotherapy. Activity of BALP significantly decreased in
      29 dogs for which postoperative samples were available. Failure of BALP activity
      to decrease after surgery was correlated with shorter survival and disease-free
      intervals. CLINICAL IMPLICATIONS: Activities of TALP and BALP in serum are
      important prognostic factors for appendicular osteosarcoma in dogs. Prognostic
      factors may help clinicians initiate more aggressive treatment for dogs that are
      at higher risk of death or relapse.

PMID- 9776999
TI  - Pharmacokinetics of a high dose of gentamicin administered intravenously or
      intramuscularly to horses.
AB  - OBJECTIVE: To evaluate pharmacokinetics of a high dose of gentamicin administered
      i.v. or i.m. to horses. DESIGN: Repeated-measures study. ANIMALS: 6 clinically
      normal female adult stock-type horses. PROCEDURE: All horses were given
      gentamicin (6.6 mg/kg [3 mg/lb] of body weight), i.v. and i.m., in a two-way
      cross-over design. Serum gentamicin concentrations were measured during a 24-hour
      period. RESULTS: Plasma concentration curves were consistent with a two
      compartment model. Maximum plasma gentamicin concentrations were 71.9 +/- 15.7
      micrograms/ml (0 hours after injection) and 22.0 +/- 4.9 micrograms/ml (1.31
      hours after injection) for the i.v. and i.m. groups, respectively. Area under the
      curve (AUC) was 116.6 +/- 14.5 and 116.3 +/- 14.6 micrograms.h/ml for the i.v.
      and i.m. groups, respectively. Elimination half-life for the IV group was 3.0 +/-
      2.8 hours. Trough concentrations were < 2 micrograms/ml for > 15 and > 12 hours
      for the i.v. and i.m. groups, respectively. Significant changes were not detected
      in clinicopathologic variables before and after administration of gentamicin.
      CLINICAL IMPLICATIONS: Administration of a high dose of gentamicin i.v. or i.m.
      resulted in peak plasma concentrations, AUC, and minimum trough plasma
      concentrations. Results indicate once-daily administration of gentamicin might be
      as efficacious and safe as multiple-dose daily administration in accordance with
      traditional low-dose regimens, similar to those used in other species.

PMID- 9777000
TI  - Reliability of using results of abdominal fluid analysis to determine treatment
      and predict lesion type and outcome for horses with colic: 218 cases (1991-1994).
AB  - OBJECTIVE: To assess clinical utility of abdominal fluid analysis in predicting
      outcome, lesion type, and whether medical or surgical treatment is indicated for
      horses with colic. DESIGN: Retrospective study. ANIMALS: 218 horses > 1 year old.
      PROCEDURE: Horses were classified on the basis of age, site of lesion, lesion
      type (nonstrangulating vs strangulating), type of treatment (medical vs
      surgical), and outcome (survival vs nonsurvival). Sensitivity and specificity of
      using age and results of abdominal fluid analysis, individually and in
      combination, to predict lesion type, type of treatment, and outcome were
      determined. RESULTS: Most single variables evaluated were found to have low
      sensitivity, specificity, and predictive value for determining lesion type,
      whether medical or surgical treatment was indicated, and outcome. When evaluated
      in series, abdominal fluid color and specific gravity had a high positive
      predictive value for lesion type, and patient age and abdominal fluid color had a
      high positive predictive value for outcome. CLINICAL IMPLICATIONS: Results of
      abdominal fluid analysis cannot be used alone to accurately predict lesion type,
      whether medical or surgical treatment is needed, or outcome for horses with
      colic.

PMID- 9777001
TI  - Arthroscopic removal of abaxial fracture fragments of the proximal sesamoid bones
      in horses: 47 cases (1989-1997).
AB  - OBJECTIVE: To determine the outcome of horses after arthroscopic removal of
      abaxial fracture fragments of the proximal sesamoid bone and association of
      fracture grade with outcome. DESIGN: Retrospective study. ANIMALS: 47 horses.
      PROCEDURE: Information obtained from dorsopalmar and dorsoplantar radiographic
      views of metacarpophalangeal and metatarsophalangeal joints was used to classify
      fractures as grade 1 (< 15 mm long), grade 2 (15 to 25 mm long), and grade 3 (>
      25 mm long) and type 1 (abaxial) and type 2 (apical-abaxial). Outcome was
      determined by whether the horse returned to its intended use, raced in the same
      class or higher (racehorses), or performed satisfactorily (nonracehorses). Number
      of starts, performance index, and money earned were also used to evaluate
      performance of racehorses. RESULTS: Follow-up information was obtained for 41
      horses (35 racehorses, 6 nonracehorses). Twenty-five racehorses were able to
      return to racing (16 in the same class, 9 in a lower class). All 6 nonracehorses
      were able to return to performance at the same level. Horses with small fracture
      fragments or fractures involving the abaxial aspect of the proximal sesamoid bone
      only had a more favorable outcome, compared with horses with large or apical
      abaxial fractures. CLINICAL IMPLICATIONS: Overall, horses with abaxial fractures
      of the proximal sesamoid bone have a favorable prognosis for return to racing,
      but only a fair prognosis for return to racing in the same class, after
      arthroscopic removal of fracture fragments. Successful results can be expected
      for nonracehorses.

PMID- 9777002
TI  - Anesthetic and cardiorespiratory effects of tiletamine-zolazepam-medetomidine in
      cheetahs.
AB  - OBJECTIVE: To evaluate anesthetic and cardiorespiratory effects of an
      intramuscular injection of a tiletamine-zolazepam-medetomidine combination in
      cheetahs. DESIGN: Prospective study. ANIMALS: 17 adult captive cheetahs.
      PROCEDURE: The anesthetic combination was administered intramuscularly via a
      dart. Induction quality, duration of lateral recumbency, duration of recovery,
      and quality of anesthetic reversal with atipamezole were assessed.
      Cardiorespiratory variables (arterial blood gas partial pressures, arterial blood
      pressure, heart and respiratory rates, end-tidal CO2, oxygen saturation, and
      rectal temperature) were measured during anesthesia. RESULTS: Sedation and
      lateral recumbency developed within 1.9 +/- 1.0 (mean +/- SD) and 4.3 +/- 2.0
      minutes of drug administration, respectively. Clinically acceptable
      cardiorespiratory and blood gas values were recorded for at least 87 minutes
      after drug administration in all but 1 cheetah. Hypoxemia and arrhythmias
      developed in 1 cheetah breathing room air but resolved after treatment with
      oxygen. Hypertension developed in all cheetahs. Significant differences in heart
      and respiratory rates, mean arterial blood pressure, arterial pH, partial
      pressure of oxygen, and hemoglobin saturation were found between cheetahs that
      did and did not receive oxygen supplementation. After administration of
      atipamezole, sternal recumbency and mobility returned within 6.9 +/- 5.8 and 47.5
      +/- 102.2 minutes, respectively. Postreversal sedation, which lasted
      approximately 4 hours, developed in 4 cheetahs. CLINICAL IMPLICATIONS: Tiletamine
      zolazepam-medetomidine delivered via a dart provided an alternative method for
      induction and maintenance of anesthesia in cheetahs. Atipamezole at the dose used
      was effective for reversal of this combination in the initial phase of
      anesthesia.

PMID- 9777003
TI  - Introducing a solid model for reconstructing the severely deformed hand.
AB  - We report a case of a 39-year-old man with a severely deformed hand resulting
      from an injury sustained in a traffic accident at 2 years of age. A Marjolin
      ulcer appeared on the cicatricial area 3 years ago. After radical surgery for
      squamous cell carcinoma, we planned to realign the axis of the ulnarly flexed
      hand. Prior to surgery, we produced a solid model of the bony framework using
      laser lithography based on 3-D CT digital image data. The solid model furnished
      us and the patient with precise information on the deformity and allowed us to
      perform preoperative simulation surgery. By a two-stage wedge-shaped ostectomy at
      the end of the radius, the ulnarly deviated axis of the hand was realigned from
      100 to 30 degrees (approximate) in clinical measurement and the patient was quite
      satisfied with the resulting function and appearance. However, there are some
      disadvantages of the laser lithography solid model: the cost is high, the resin
      material is very hard and difficult to operate on, and the model does not include
      soft-tissue structures. The development of a model in the future that includes
      vessels, nerves, and tendons will enable surgeons to transfer more precisely the
      results of the simulation surgery to the patient in the operating room.

PMID- 9777004
TI  - M-type potassium current in dissociated sympathetic ganglion cells of Xenopus
      laevis.
AB  - Whole-cell/voltage-clamp recordings were made from dissociated sympathetic
      neurons of Xenopus laevis. Step depolarization (10-70 mV, 0.5 s) from the holding
      potential of -65 mV activated a non-inactivating potassium current which was
      selectively blocked by barium (1 mM). The current did not require an inward
      calcium current for its activation. The steady-state activation curve of the
      current was centered at -35 mV with a slope factor of 8.6 mV. The time constant
      for activation of the current was about 115 ms when measured at -35 mV and the
      effective valence of the voltage-sensing particle was 2.9. This potassium current
      was identified as a particular set of potassium currents usually referred to as M
      current.

PMID- 9777005
TI  - Left atrial ball thrombus in a patient without mitral valve disease.
AB  - We experienced a large left atrial ball thrombus in a patient without mitral
      valve disease. By transthoracic echocardiography the mass was appeared to be free
      floating and swinging randomly in the left atrium. An urgent operation was
      performed successfully. Operative findings revealed the mass to be a large ball
      thrombus loosely attached to atrial wall. We suggest that surgical removal is
      indicated as soon as possible, because of a very high risk of embolism or
      circulatory collapse.

PMID- 9777006
TI  - The bioavailability and pharmacokinetics of mefenamic acid in alloxan-diabetic
      rabbits.
AB  - The bioavailability and pharmacokinetics of mefenamic acid was studied in alloxan
      diabetic rabbits. Mefenamic acid in plasma was assayed by high performance liquid
      chromatography. A paired t-test for normal and alloxan treated rabbits revealed a
      significant decrease in all the bioavailability and disposition kinetic
      parameters of mefenamic acid during diabetes was observed in the present study.
      The altered bioavailability and disposition of mefenamic acid in the diabetic
      state will require adjustment of the dosage regimen prescribed for diabetics in a
      clinical setting.

PMID- 9777007
TI  - IgA nephropathy in mice following repeated administration of conjugated
      Haemophilus influenzae type B vaccine (PRP-T).
AB  - OBJECTIVE: In this study, the risk of IgA nephropathy in Swiss albino mice
      following the subcutaneous administration of conjugated Haemophilus influenzae
      type b vaccine (PRP-T), containing capsular polysaccharide of the organism (PRP)
      conjugated to tetanus protein (T), was evaluated. METHODS: Three treatment and
      corresponding control groups, each containing mice, were constituted and given 2,
      4, 6 injections of 1/4 HD of PRP-T or placebo, respectively, at 2-week intervals.
      All mice in each treatment group were sacrificed two weeks from the last
      injection to examine sequential glomerular changes. RESULTS: The niceoscpic
      examination of renal tissues revealed mesangial proliferation (6/7; 85%) in the
      first group given 2 doses of vaccine; mesangial proliferation (5/7; 72%) and
      increase in matrix (7/7; 100%) in the second group given 4 doses; and mesangial
      proliferation (7/7; 100%), increase in matrix (7/7; 100%), IgA (7/7; 100%) and C3
      (3/7; 42%) deposition within mesangium in the third group given 6 doses. No
      histopathological changes were detected in the renal tissues of any control
      mouse. When the experimental groups were compared statistically with their
      respective controls at the light microscopic level, mesangial proliferation in
      the first group (p: 0.0047), mesangial proliferation (p: 0.021) and increase in
      matrix (p: 0.001) in the second group, mesengial proliferation (p: 0.001) and
      increase in matrix (p: 0.001) in the third group were determined to be
      significantly different. When study and control groups were compared by
      immunofluorescence microscopy, only the third group revealed a statistically
      significant difference with respect to IgA deposition (p: 0.001). C3 deposition
      was also demonstrated in this group, but it was not significantly different (p:
      0.192). However, in no instance was a control mouse found to have any form of
      immune deposition. CONCLUSION: We concluded that conjugated Haemophilus
      influenzae type b vaccine, given at two-week intervals to a total of six doses,
      caused secondary IgA nephropathy in mice.

PMID- 9777008
TI  - Radioautographology: the proposal of a new concept.
AB  - A new concept termed "radioautographology" is advocated. This term was
      synthesized from "radioautography" and "ology", expressing a new science derived
      from radioautography. The concept of radioautographology (RAGology) is that of a
      science whose objective is to localize radioactive substances in the biological
      structure of objects and to analyze and study the significance of these
      substances in the biological structure. On the other hand, the old term
      radioautography (RAG) is the technique used to demonstrate the pattern of
      localization of various radiolabeled compounds in specimens. The specimens used
      in biology and medicine are cells and tissues. They are fixed, sectioned and
      placed in contact with the radioautographic emulsions, which are exposed and
      developed to produce metallic silver grains. Such specimens are designated as
      radioautographs and the patterns of pictures made of silver grains are named
      radioautograms. The technicians who produce radioautographs are named
      radioautographers, while those who study RAGology are scientists and should be
      called radioautographologists. The science of RAGology can be divided into two
      parts, general RAGology and special RAGology, as most natural sciences usually
      can. General RAGology is the technology of RAG which consists of three fields of
      science, i.e., physics concerning radioactivity, histochemistry for the treatment
      of cells and tissues, and photochemistry dealing with the photographic emulsions.
      Special RAGology, on the other hand, consists of applications of general
      RAGology. The applications can be classified into several scientific fields,
      i.e., cellular and molecular biology, anatomy, histology, embryology, pathology
      and pharmacology. Studies carried out in our laboratory are summarized and
      reviewed. All the results obtained from such applications should be systematized
      as a new field of science in the future.

PMID- 9777009
TI  - E. coli alpha-hemolysin: a membrane-active protein toxin.
AB  - alpha-Hemolysin is synthesized as a 1024-amino acid polypeptide, then
      intracellularly activated by specific fatty acylation. A second activation step
      takes place in the extracellular medium through binding of Ca2+ ions. Even in the
      absence of fatty acids and Ca2+ HlyA is an amphipathic protein, with a tendency
      to self-aggregation. However, Ca(2+)-binding appears to expose hydrophobic
      patches on the protein surface, facilitating both self-aggregation and
      irreversible insertion into membranes. The protein may somehow bind membranes in
      the absence of divalent cations, but only when Ca2+ (or Sr2+, or Ba2+) is bound
      to the toxin in aqueous suspensions, i.e., prior to its interaction with
      bilayers, can alpha-hemolysin bind irreversibly model or cell membranes in such a
      way that the integrity of the membrane barrier is lost, and cell or vesicle
      leakage ensues. Leakage is not due to the formation of proteinaceous pores, but
      rather to the transient disruption of the bilayer, due to the protein insertion
      into the outer membrane monolayer, and subsequent perturbations in the bilayer
      lateral tension. Protein or glycoprotein receptors for alpha-hemolysin may exist
      on the cell surface, but the toxin is also active on pure lipid bilayers.

PMID- 9777010
TI  - The use of non-human primates as animal models for the study of hepatitis
      viruses.
AB  - Hepatitis viruses belong to different families and have in common a striking
      hepatotropism and restrictions for propagation in cell culture. The
      transmissibility of hepatitis is in great part limited to non-human primates.
      Enterically transmitted hepatitis viruses (hepatitis A virus and hepatitis E
      virus) can induce hepatitis in a number of Old World and New World monkey
      species, while the host range of non-human primates susceptible to hepatitis
      viruses transmitted by the parenteral route (hepatitis B virus, hepatitis C virus
      and hepatitis delta virus) is restricted to few species of Old World monkeys,
      especially the chimpanzee. Experimental studies on non-human primates have
      provided an invaluable source of information regarding the biology and
      pathogenesis of these viruses, and represent a still indispensable tool for
      vaccine and drug testing.

PMID- 9777011
TI  - Involvement of the actin cytoskeleton and p21rho-family GTPases in the
      pathogenesis of the human protozoan parasite Entamoeba histolytica.
AB  - It has been estimated that infection with the enteric protozoan parasite
      Entamoeba histolytica kills more than 50,000 people a year. Central to the
      pathogenesis of this organism is its ability to directly lyse host cells and
      cause tissue destruction. Amebic lesions show evidence of cell lysis, tissue
      necrosis, and damage to the extracellular matrix. The specific molecular
      mechanisms by which these events are initiated, transmitted, and effected are
      just beginning to be uncovered. In this article we review what is known about
      host cell adherence and contact-dependent cytolysis. We cover the involvement of
      the actin cytoskeleton and small GTP-binding proteins of the p21rho-family in the
      process of cell killing and phagocytosis, and also look at how amebic
      interactions with molecules of the extracellular matrix contribute to its
      cytopathic effects.

PMID- 9777012
TI  - Effect of hypoxia on the activity and binding of glycolytic and associated
      enzymes in sea scorpion tissues.
AB  - The effect of hypoxia on the levels of glycogen, glucose and lactate as well as
      the activities and binding of glycolytic and associated enzymes to subcellular
      structures was studied in brain, liver and white muscle of the teleost fish,
      Scorpaena porcus. Hypoxia exposure decreased glucose levels in liver from 2.53 to
      1.70 mumol/g wet weight and in muscle led to its increase from 3.64 to 25.1
      mumol/g wet weight. Maximal activities of several enzymes in brain were increased
      by hypoxia: hexokinase by 23%, phosphoglucoisomerase by 47% and
      phosphofructokinase (PFK) by 56%. However, activities of other enzymes in brain
      as well as enzymes in liver and white muscle were largely unchanged or decreased
      during experimental hypoxia. Glycolytic enzymes in all three tissues were
      partitioned between soluble and particulate-bound forms. In several cases, the
      percentage of bound enzymes was reduced during hypoxia; bound aldolase in brain
      was reduced from 36.4 to 30.3% whereas glucose-6-phosphate dehydrogenase fell
      from 55.7 to 28.7% bound. In muscle PFK was reduced from 57.4 to 41.7% bound.
      Oppositely, the proportion of bound aldolase and triosephosphate isomerase
      increased in hypoxic muscle. Phosphoglucomutase did not appear to occur in a
      bound form in liver and bound phosphoglucomutase disappeared in muscle during
      hypoxia exposure. Anoxia exposure also led to the disappearance of bound fructose
      1,6-bisphosphatase in liver, whereas a bound fraction of this enzyme appeared in
      white muscle of anoxic animals. The possible function of reversible binding of
      glycolytic enzymes to subcellular structures as a regulatory mechanism of
      carbohydrate metabolism is discussed.

PMID- 9777013
TI  - Annual changes in serum calcium and inorganic phosphate levels and correlation
      with gonadal status of a freshwater murrel, Channa punctatus (Bloch).
AB  - Adult Channa punctatus murrels of both sexes (60-80 g) were collected locally
      from Ramgarh Lake during the second week of every month (10 individuals of each
      sex/month) throughout the year. Blood samples were collected and analyzed for
      serum calcium and phosphate levels by the methods of Trinder (1960) and Fiske and
      Subbarow (1925), respectively. Gonads were fixed to judge the state of maturation
      of the fish. Males exhibited no change in serum calcium levels throughout the
      year in correlation with testicular maturation. However, serum phosphate levels
      exhibited a rise in correlation with the increased gonadosomatic index. Females
      showed marked seasonal changes in serum calcium and phosphate levels which were
      associated with ovarian maturation (vitellogenesis).

PMID- 9777014
TI  - Antioxidant activity of the microalga Spirulina maxima.
AB  - Spirulina maxima, which is used as a food additive, is a microalga rich in
      protein and other essential nutrients. Spirulina contains phenolic acids,
      tocopherols and beta-carotene which are known to exhibit antioxidant properties.
      The aim of the present study was to evaluate the antioxidant capacity of a
      Spirulina extract. The antioxidant activity of a methanolic extract of Spirulina
      was determined in vitro and in vivo. The in vitro antioxidant capacity was tested
      on a brain homogenate incubated with and without the extract at 37 degrees C. The
      IC50 (concentration which causes a 50% reduction of oxidation) of the extract in
      this system was 0.18 mg/ml. The in vivo antioxidant capacity was evaluated in
      plasma and liver of animals receiving a daily dose of 5 mg for 2 and 7 weeks.
      Plasma antioxidant capacity was measured in brain homogenate incubated for 1 h at
      37 degrees C. The production of oxidized compounds in liver after 2 h of
      incubation at 37 degrees C was measured in terms of thiobarbituric acid reactant
      substances (TBARS) in control and experimental groups. Upon treatment, the
      antioxidant capacity of plasma was 71% for the experimental group and 54% for the
      control group. Data from liver spontaneous peroxidation studies were not
      significantly different between groups. The amounts of phenolic acids, alpha
      tocopherol and beta-carotene were determined in Spirulina extracts. The results
      obtained indicate that Spirulina provides some antioxidant protection for both in
      vitro and in vivo systems.

PMID- 9777015
TI  - Improvement of the indirect hemagglutination test for the detection of antibodies
      to Streptococcus pyogenes.
AB  - An indirect hemagglutination test for a seroepidemiological survey of
      Streptococcus pyogenes infection was standardized. This is an improved
      modification of the indirect hemagglutination test which utilizes an unstable
      reagent prepared with fresh blood cells. Two types of bacterial antigens
      represented by extracellular products and purified streptolysin O were assayed,
      but only the former antigen gave good results. Pretreatment of the bacterial
      antigen with 0.15 M NaOH and neutralization to pH 5.5, as well as postfixation of
      sensitized red cells with 0.1% glutaraldehyde at 56 degrees C for 30 min were
      found to be essential to give long stability to the reagent in liquid suspension,
      at least 9 months at 4 degrees C. A total of 564 serum samples with high,
      moderate and low anti-streptolysin O antibodies as determined by the
      neutralization assay were studied by the indirect hemagglutination test using the
      new reagent. The sensitivity, specificity, efficiency, positive predictive value
      and negative predictive value of the test in relation to the neutralization assay
      were 0.950, 0.975, 0.963, 0.973, and 0.955, respectively. The kappa agreement
      index between the two techniques was high (0.926) and ranked as "almost perfect".
      Antibody levels detected by both techniques also presented a high positive
      correlation (rs = 0.726). Five reagent batches successively produced proved to be
      reproducible. Thus, the improved indirect hemagglutination test seems to be
      useful for public health laboratories.

PMID- 9777016
TI  - Anterograde effects of a single electroconvulsive shock on inhibitory avoidance
      and on cued fear conditioning.
AB  - A single electroconvulsive shock (ECS) or a sham ECS was administered to male 3-4
      month-old Wistar rats 1, 2, and 4 h before training in an inhibitory avoidance
      test and in cued classical fear conditioning (measured by means of freezing time
      in a new environment). ECS impaired inhibitory avoidance at all times and, at 1
      or 2 h before training, reduced freezing time before and after re-presentation of
      the ECS. These results are interpreted as a transient conditioned stimulus (CS)
      induced anxiolytic or analgesic effect lasting about 2 h after a single
      treatment, in addition to the known amnesic effect of the stimulus. This suggests
      that the effect of anterograde learning impairment is demonstrated unequivocally
      only when the analgesic/anxiolytic effect is over (about 4 h after ECS
      administration) and that this impairment of learning is selective, affecting
      inhibitory avoidance but not classical fear conditioning to a discrete stimulus.

PMID- 9777017
TI  - The radioprotective effect of a new aminothiol (20-PRA).
AB  - We examined the radioprotective effect of aminothiol 2-N-propylamine-cyclo
      hexanethiol (20-PRA) on a human leukemic cell line (K562) following various
      radiation doses (5, 7.5 and 20 Gy) using a source of 60Co gamma-rays. At 5 Gy and
      1 nM 20-PRA, a substantial protective effect (58%) was seen 24 h after
      irradiation, followed by a decrease at 48 h (11%). At the high radiation dose (20
      Gy) a low protective effect was also seen (35%). In addition, the antitumorigenic
      potential of 10 nM 20-PRA was shown by the inhibition of crown gall formation
      induced by Agrobacterium tumefaciens. The radioprotective potency of 20-PRA is
      10(5)-10(6) times higher than that of the aminothiol WR-1065 (N-(2-mercaptoethyl)
      1,3-diaminopropane) whose protective effect is in the 0.1 to 1.0 mM range.

PMID- 9777018
TI  - High dietary calcium decreases blood pressure in normotensive rats.
AB  - This study evaluates the influence of different concentrations of calcium on
      blood pressure of normotensive rats. Four groups of Wistar rats (A, B, C and D)
      had free access to modified isocaloric and isoproteic diets containing 0.2, 0.5,
      2 and 4 g% calcium as calcium carbonate for a period of 30 days. Systolic and
      diastolic arterial blood pressures were monitored in awake rats by the indirect
      tail cuff method using a Physiograph equipped with transducers and preamplifiers.
      Body weight and length and food intake were monitored. Under the conditions of
      the present experiment, the systolic and diastolic arterial blood pressures of
      group D rats fed a diet containing 4 g% calcium were significantly (P < 0.05)
      lower compared to rats of the other groups.

PMID- 9777019
TI  - Swelling-induced decrease in spontaneous pacemaker activity of rabbit isolated
      sino-atrial node cells.
AB  - The heart responds to an increase in sino-atrial node wall stress with an
      augmentation in rate of contraction. It has been suggested that swelling
      activated ion channels may play a key role in that response. This paper
      investigates directly the effects of cell swelling on spontaneous activity of
      rabbit isolated sino-atrial node pacemaker cells. The main finding is that sino
      atrial node cells, studied in current clamp mode using amphotericin-permeabilized
      patches, decrease their spontaneous pacemaker rate by 24.2 +/- 7.8% (P < 0.01, n
      = 9) during 75% hyposmotic swelling. This response is opposite to the predicted
      impact of volume-activation of sarcolemmal ion conductances. Computer modelling
      (OXSOFT Heart v4.8) suggests that swelling-induced dilution of the cytosol,
      reduction in intracellular potassium concentration, and decrease in the delayed
      rectifier potassium current, IK, are leading mechanisms in the response. This is
      supported by voltage-clamp data that show a swelling-induced positive shift in
      the reversal potential of IK by between 5 and 10 mV (n = 7) and a reduction in
      amplitude of its rapidly activating component, IKr, (n = 6). Thus, spontaneously
      active sino-atrial node cells reduce pacemaking rate during swelling. This
      response cannot be explained by the known volume-activated sarcolemmal ion
      conductances, but appears to be dictated by other mechanisms including dilution
      of the cytosol and reduction in IK. The results re-enforce the view that cardiac
      responses to cell volume changes may be quite different from those to
      longitudinal stretch.

PMID- 9777020
TI  - Partial inhibition of Na,K-ATPase activity in cultured rabbit non-pigmented
      ciliary epithelium following an episode of cytoplasmic ATP depletion.
AB  - Ouabain-sensitive ATP hydrolysis (Na,K-ATPase activity) was measured in digitonin
      permeabilized monolayers of cultured cells derived from rabbit non-pigmented
      ciliary epithelium. Diminished Na,K-ATPase activity was observed in cells that
      had been pre-treated 10 min with the protein kinase C activator, PDBu, as well as
      in cells that had been cooled to 4 degrees C for 4 h then rewarmed to 37 degrees
      C for 30 min (cool-rewarm manoeuvre). In the intact cells, ouabain binding was
      not decreased either by PDBu treatment or the cool-rewarm manoeuvre. However,
      both PDBu and the cool-rewarm manoeuvre increased the rate of ouabain-sensitive
      potassium (86Rb) uptake measured in intact cells. Cell ATP content was diminished
      in PDBu-treated cells and cells subjected to the cool-rewarm manoeuvre. We
      suggest that an episode of ATP depletion might initiate a mechanism which causes
      lasting, partial inhibition of Na,K-ATPase activity. In keeping with this
      suggestion, diminished Na,K-ATPase activity was observed in cells that had been
      pre-treated 20 min with the metabolic inhibitors CCCP or rotenone and in cells
      pre-treated 2.5 h in dextrose-free medium. This study illustrates that Na,K
      ATPase activity measured in the permeabilized cell is a complex parameter which
      is not necessarily a reliable indicator of sodium pump responses in the intact
      cell.

PMID- 9777022
TI  - Renal tubular transport and metabolism of carboxyamidated and glycine-extended
      gastrins in pigs.
AB  - Renal handling of postprandial and intravenously administered gastrin was
      investigated in anaesthetised pigs. The fractional extraction of postprandial
      carboxyamidated and glycine-extended gastrin in the kidneys was 0.21 +/- 0.01 and
      0.16 +/- 0.02, but the respective urinary clearance comprised only 0.57 +/- 0.03
      and 0.44 +/- 0.05% of the GFR (P < 0.02). The respective total body clearance of
      carboxyamidated and glycine-extended gastrin-17 (gastrin-17 and gastrin-17Gly)
      during continuous infusion was 22.9 +/- 1.5 and 19.6 +/- 1.4 mL kg-1 min-1 (NS),
      and the renal fractional extraction of the peptides was 0.31 +/- 0.03 and 0.29 +/
      0.05, respectively. The kidneys accounted for 8% of total body clearance of
      gastrin-17. Renal filtration rate of gastrin-17 exceeded renal extraction rate
      (9.739 +/- 0.487 vs. 6.407 +/- 0.321 pmol min-1). Urinary clearance of gastrin-17
      and gastrin-17Gly amounted only 0.91 +/- 0.16 and 0.13 +/- 0.03%, respectively,
      of the GFR (P < 0.01), but urinary excretion rate correlated with the filtered
      amount of the peptides (r = 0.93, P < 0.01). Neither was a renal plasma threshold
      recorded nor was a Tm value for tubular uptake or degradation of gastrin achieved
      in spite of supraphysiological plasma levels of the peptides. The results
      indicate that filtered gastrin is almost completely removed in the renal tubules,
      primary by metabolism although part of the absorbed peptides may be returned to
      the circulation in intact form. The process for uptake or metabolism has a high
      capacity but varies with the molecular form of gastrin.

PMID- 9777021
TI  - Increased endothelin ETB contractile activity in cultured segments of human
      temporal artery.
AB  - Contractions induced by endothelin-1, endothelin-3 and the selective ETB agonist,
      sarafotoxin S6c, were studied in segments of human temporal artery. The results
      in fresh arteries were compared with those obtained after 1 or 4 days in organ
      culture, and with the specific ETA antagonist FR 139,317, the specific, mixed
      antagonist bosentan, or the specific ETB antagonist, BQ 788. Sarafotoxin S6c
      induced no contractile activity in fresh artery segments, but elicited marked
      contractions after culture. This contraction was only slightly inhibited by FR
      139,317, but was abolished by BQ 788. Contractions induced by endothelin-1 were
      antagonized by FR 139,317 and bosentan, but not by BQ 788. Organ culture did not
      change the overall pattern, but all concentration-response curves were shifted
      leftwards. Contractions induced by endothelin-3 were abolished by all antagonists
      in fresh arteries, but some activity was restored after organ culture.
      Sensitivity to endothelin-3 was markedly increased. The results suggest a change
      in endothelin receptors during organ culture, resulting in a marked increase in
      contractile ETB activity, and possibly some increase in ETA activity. Such
      changes illustrate the complexity of endothelin responses in this vascular bed.

PMID- 9777023
TI  - Forskolin-induced down-regulation of Na+,K(+)-ATPase activity is not associated
      with internalization of the enzyme.
AB  - Activation by protein kinase A by forskolin phosphorylates and inactivates
      Na+,K(+)-ATPase in COS-7 cells (Cheng et al. 1997b). In this study we show, using
      [3H]ouabain binding, that forskolin-induced inhibition of Na+,K(+)-ATPase
      activity is not because of internalization of the enzyme. The effect of forskolin
      on Na+,K(+)-ATPase activity was examined by two independent methods, ouabain
      sensitive 86Rb+ uptake in intact cells and ATP hydrolysis in microsomal
      preparations from cells. The change in number of functional pumps on cell surface
      before and after protein kinase A activation was assessed by [3H]ouabain binding
      measured under equilibrium conditions. Cells, which had been ATP-depleted by
      antimycin A and 2-deoxyglucose treatment, served as a positive control for the
      internalization of Na+,K(+)-ATPase. Activation of protein kinase A with forskolin
      in combination with the phosphodiesterase inhibitor 3-isobutyl-1-methyl xanthine,
      inhibited Na+,K(+)-ATPase activity, but this treatment had no effect on specific
      ouabain binding. No change in ouabain binding was found following activation of
      protein kinase C by phorbol ester or diacyl glycerol analogue treatment in cells.
      These data suggest that protein kinase A phosphorylation and inhibition of
      Na+,K(+)-ATPase activity does not lead to any internalization of the enzyme in
      COS-7 cells.

PMID- 9777024
TI  - Bradykinin causes contraction in rat uterus through the same signal pathway as
      oxytocin.
AB  - The signal pathway for bradykinin-induced contraction of the uterine smooth
      muscle was investigated by comparing the effect of blocking agents on bradykinin
      and oxytocin induced contractions of the isolated rat uterus in organ bath. The
      phospholipase C inhibitor U-73,122 abolished the effect of both bradykinin and
      oxytocin. Inhibition of non-voltage-dependent Ca2+ influx by SK & F 96,365
      reduced the contraction induced by both agonists to about 20% of control. The
      tissues failed to contract when they were exposed to bradykinin or oxytocin in
      Ca(2+)-free Krebs-Henseleit buffer with 2 mM EDTA. Both bradykinin and oxytocin
      induced further contraction when the tissues were partially depolarized and
      partially contracted by 30 mM KCl. These observations suggest that bradykinin,
      like oxytocin, activates phospholipase C which generates IP3 with a subsequent
      release of Ca2+ from intracellular stores followed by store-operated Ca2+ influx.
      Thus, membrane potential independent steps appear to be important in bradykinin
      induced contraction in the rat uterus.

PMID- 9777025
TI  - Cardiac accumulation of citrate during brief myocardial ischaemia and reperfusion
      in the pig in vivo.
AB  - Citrate is a key intermediate in energy metabolism and an inhibitor of
      phosphofructokinase of the glycolytic pathway. During myocardial ischaemia
      glycolysis is the main source of cardiac ATP. The aim of the present study was to
      determine if myocardial ischaemia and reperfusion alter cardiac tissue levels of
      citrate. Open-chest, anaesthetized pigs were subjected to 10 min of regional
      myocardial ischaemia by occlusion of the left anterior descending coronary
      artery, with and without reperfusion, and to 10 min of global ischaemia by
      circulatory arrest. Citrate, amino acids, glucose and NH3 were measured in
      biopsies. Ischaemia, whether regional or global, caused a 60-70% increase in
      tissue levels of citrate. During 1 min of reperfusion following regional
      ischaemia the level of citrate increased 460%, to approximately 600 nmol g-1 wet
      weight. The level of glutamate decreased by 20-33% (corresponding to 1300-2200
      nmol g-1 wet weight), indicating net consumption of this amino acid during
      ischaemia. The level of aspartate decreased 50% indicating conversion of
      aspartate to oxaloacetate for the synthesis of citrate. Theoretically, the
      accumulation of myocardial citrate during brief ischaemia and early reperfusion
      is large enough to significantly inhibit phosphofructokinase activity and could
      therefore affect the ability of the myocardium to increase the glycolytic rate in
      response to ischaemia. This could, however, be partly compensated by the
      metabolism of myocardial glutamate.

PMID- 9777026
TI  - Microsphere infusion reverses vasoconstrictor-mediated change in hindlimb oxygen
      uptake and energy status.
AB  - The vasoconstrictors, angiotensin II (AII) and serotonin (5-HT) produce opposing
      metabolic effects and appear to control different flow routes in the constant
      flow perfused rat hindlimb. In the present study the association between vascular
      flow route recruitment and metabolism was assessed by selective microsphere
      embolism of either route. Microspheres (MS, 11.9 +/- 0.1 microns, mean +/- SE
      diameter) were injected during AII, 5-HT or vehicle infusions (basal conditions)
      and the effects on hindlimb (4.7 +/- 0.1 g muscle) oxygen uptake (VO2) and
      indices of energy status CrP/Cr, CrP/ATP and energy charge (EC) of the calf
      muscle group assessed. MS (1.5 x 10(6)) injected during vehicle, or 5-HT infusion
      increased VO2 (P < 0.05) but did not affect energy status. During AII, MS
      decreased VO2. Change in VO2 correlated positively with CrP/Cr (r = 0.68, P <
      0.0001) and CrP/ATP (r = 0.51, P < 0.001) but not EC (r = 0.08, P = 0.59). MS
      (1.5 x 10(6)) increased pressure but did not affect the flow rate. The metabolic
      changes resulting from 1.5 x 10(6) microspheres were intensified by a second
      injection of 1.5 x 10(6) microspheres but further injection (> 3.0 x 10(6)
      microspheres) began to inhibit flow. It is concluded that a finite number (< or =
      3.0 x 10(6)) of microspheres of 11.9 microns diameter has opposite effects on VO2
      depending on the vasoconstrictor present and that these effects result from the
      occlusion of the different vascular route accessed by each vasoconstrictor. The
      data support the proposal that hindlimb metabolism can be controlled by
      vasoconstrictors as a result of selective vascular recruitment.

PMID- 9777027
TI  - Regional differences in the effect of exercise intensity on thermoregulatory
      sweating and cutaneous vasodilation.
AB  - To investigate regional body differences in the effect of exercise intensity on
      the thermoregulatory sweating response, nine healthy male subjects (23.2 +/- 0.4
      year) cycled at 35, 50 and 65% of their maximal O2 uptake (VO2max) for 30 min at
      an ambient temperature of 28.3 +/- 0.2 degrees C and a relative humidity of 42.6
      +/- 2.4%. Local sweating rate (msw) on the forehead, chest, back, forearm and
      thigh increased significantly with increases in the exercise intensity from 35 to
      50% VO2max and from 50 to 65% VO2max (P < 0.05). The mean values for the density
      of activated sweat glands (ASG) at 50 and 65% VO2max at the five sites were
      significantly greater than at 35% VO2max. The mean value of the sweat output per
      gland (SGO) also increased significantly with the increase in exercise intensity
      (P < 0.05). The patterns of changes in ASG and SGO with an increase in exercise
      intensity differed from one region of the body to another. Although esophageal
      temperature (Tes) threshold for the onset of sweating at each site was not
      altered by exercise intensity, the sensitivity of the sweating response on the
      forehead increased significantly from 35 to 50 and 65% VO2max (P < 0.05). The
      threshold for cutaneous vasodilation tend to increase with exercise intensity,
      although the exercise intensity did not affect the sensitivity (the slope in the
      relationship Tes vs. percentage of the maximal skin blood flow) at each site. Tes
      threshold for cutaneous vasodilation on the forearm was significantly higher at
      65% VO2max than at either 35 or 50% VO2max, but this was not observed at the
      other sites, such as on the forehead and chest. These results suggest that the
      increase in msw seen with an increasing intensity of exercise depends first on
      ASG, and then on SGO, and the dependence of ASG and SGO on the increase in msw
      differs for different body sites. In addition, there are regional differences in
      the Tes threshold for vasodilation in response to an increase in exercise
      intensity.

PMID- 9777028
TI  - Rapid recovery of power output in females.
AB  - The purpose of the present study was to examine whether the magnitude of the
      changes in the concentration of muscle metabolites influences the recovery of
      power output following short-term maximal intensity cycle exercise performed at
      different average pedalling rates. In part A of the study eight female subjects
      performed four trials on a cycle ergometer. Two trials involved maximal sprints
      of 30- and 6-s duration separated by a very short (2-3 s) recovery period.
      Average pedal rate during the first 30-s sprint was manipulated by employing
      resistances of either 7.5 or 10.1% of body weight; the second sprint always being
      performed against 7.5% BW. In two further trials subjects performed only a single
      30-s sprint against the two resistances with pre- and post-exercise muscle
      biopsies and blood samples being taken. Peak power in the second sprint was
      significantly higher (442 +/- 31W vs. 402 +/- 33W; P < 0.05) following prior
      exercise against the greater resistance during which average pedal rate was lower
      (approximately 26%; P < 0.01) compared with the lesser resistance. However,
      despite this the muscle metabolite responses to the first sprint were similar
      (delta PCr (7.5 vs. 10.1% applied resistance) -55 vs. -59 mmol kg dry muscle-1:
      delta Lactate + 104 vs. +107 mmol kg dry muscle-1: both P > 0.05). In part B of
      the study six female subjects performed 19 trials in which the recovery interval
      between a maximal 30-s sprint (where average pedalling rate was manipulated in a
      manner similar to part A) and a 6-s sprint ranged from 0 to 300 s. The rate of
      restoration of power output was influenced by the average pedal rate in sprint 1
      only for recovery durations of up to 3 s. These findings suggest that the
      recovery of power is not exclusively determined by muscle metabolites, in
      particular PCr, when the recovery duration is very short (< or = 3 s). As it has
      been previously shown that the pattern of muscle activation influences ionic
      balance it is speculated that ionic factors may be very important in the early
      and rapid recovery of power.

PMID- 9777029
TI  - The influence of PaO2, pH and SaO2 on maximal oxygen uptake.
AB  - Influence of arterial oxygen pressure (PaO2) and pH on haemoglobin saturation
      (SaO2) and in turn on O2 uptake (VO2) was evaluated during ergometer rowing (156,
      276 and 376 W; VO2max, 5.0 L min-1; n = 11). During low intensity exercise,
      neither pH nor SaO2 were affected significantly. In response to the higher work
      intensities, ventilations (VE) of 129 +/- 10 and 155 +/- 8 L min-1 enhanced the
      end tidal PO2 (PETO2) to the same extent (117 +/- 2 mmHg), but PaO2 became
      reduced (from 102 +/- 2 to 78 +/- 2 and 81 +/- 3 mmHg, respectively). As pH
      decreased during maximal exercise (7.14 +/- 0.02 vs. 7.30 +/- 0.02), SaO2 also
      became lower (92.9 +/- 0.7 vs. 95.1 +/- 0.1%) and arterial O2 content (CaO2) was
      202 +/- 3 mL L-1. An inspired O2 fraction (F1O2) of 0.30 (n = 8) did not affect
      VE, but increased PETO2 and PaO2 to 175 +/- 4 and 164 +/- 5 mmHg and the PETO2
      PaO2 difference was reduced (21 +/- 4 vs. 36 +/- 4 mmHg). pH did not change when
      compared with normoxia and SaO2 remained within 1% of the level at rest in
      hyperoxia (99 +/- 0.1%). Thus, CaO2 and VO2max increased to 212 +/- 3 mL L-1 and
      5.7 +/- 0.2 L min-1, respectively. The reduced PaO2 became of importance for SaO2
      when a low pH inhibited the affinity of O2 to haemoglobin. An increased F1O2
      reduced the gradient over the alveolar-arterial membrane, maintained haemoglobin
      saturation despite the reduction in pH and resulted in increases of the arterial
      oxygen content and uptake.

PMID- 9777030
TI  - Proximal tubular function in adult rats treated neonatally with enalapril.
AB  - Neonatal treatment with angiotensin-converting enzyme (ACE) inhibitors or the
      angiotensin II type-1 receptor antagonist losartan in rats induces irreversible
      renal histological abnormalities, mainly papillary atrophy, in association with
      an impairment in urinary concentrating ability. The aim of the present study was
      to assess proximal tubular function in adult rats treated neonatally with
      enalapril. Male Wistar rats received daily, intraperitoneal injections of either
      enalapril (10 mg kg-1) or isotonic saline vehicle from 3 to 24 days of age. In 15
      week-old, hydropenic rats we analysed: (i) proximal tubular iso-osmotic fluid
      reabsorption using the method of lithium clearance; and (ii) maximal tubular D
      glucose reabsorption (TmG), under pentobarbital anaesthesia. The main findings
      were that neonatally enalapril-treated rats showed: (i) reductions in absolute
      (APRH2O) and fractional (FPRH2O) iso-osmotic fluid reabsorption in the proximal
      tubules (APRH2O: 0.50 +/- 0.02 vs. 0.64 +/- 0.03 mL min-1 g KW-1, P < 0.05;
      FPRH2O: 58 +/- 3 vs. 68 +/- 2%, P < 0.05); and (ii) a normal TmG. In addition,
      during baseline clearance measurements neonatally enalapril-treated rats showed
      increases in urine volume and fractional excretion rates of sodium and potassium,
      a reduction in urine osmolality, whereas glomerular filtration rate and effective
      renal plasma flow were unaltered. These results suggest that neonatal ACE
      inhibition produces an irreversible, but differentiated, abnormality in proximal
      tubular function. Thus, the development of a normal proximal tubular function in
      the rat seems to be dependent on an intact renin-angiotensin system, (RAS)
      neonatally.

PMID- 9777031
TI  - Regulation of cell cyclic AMP in medullary thick ascending limb of Henle in a rat
      model of chronic renal failure.
AB  - Chronic renal failure (CRF) is accompanied by adaptive changes in electrolyte
      reabsorption in the thick ascending limb of Henle of surviving nephrons. To study
      the cellular mechanism of this adaptation, we measured intracellular cAMP in
      micro-dissected medullary thick ascending limb (mTAL) segments in rats with CRF.
      mTAL exhibited in CRF an increase of basal cAMP from 25.6 +/- 10.0 in controls to
      65.8 +/- 11.3 fmol mm-1 tubule in CRF (P < 0.05). Vasopressin and calcitonin
      stimulated mTAL adenylate-cyclase in a dose-dependent manner in controls but
      failed to stimulate in CRF. Likewise, maximal stimulation with 10(-3) M 3
      isobutyl-1-methylxanthine (IBMX) plus 10(-5) M forskolin increased cAMP in
      controls to 63.0 +/- 16.0 but not in CRF, where maximal stimulated values
      remained at 63.1 +/- 18.8 fmol mm-1 tubule (P NS). Alpha2-adrenoreceptor
      activation with clonidine at concentrations ranging from 10(-8) to 10(-6) M
      diminished cAMP production by 37% in CRF (P < 0.05), whereas no differences were
      found in controls. Thus, the basal intracellular cAMP is increased in rat mTAL in
      CRF. The finding that neither forskolin nor vasopressin were able to further
      augment intracellular cAMP would suggest that stimulatory pathways of the
      adenylate-cyclase system are activated in the basal state. However, mTAL cells in
      CRF seem to retain the response of normal epithelium to inhibitory pathways such
      as the one mediated by alpha2-adrenoreceptors.

PMID- 9777032
TI  - Opposite effects of adrenaline on plasma ammonia and blood lactate levels in
      humans.

PMID- 9777033
TI  - Possible beta 3-adrenoceptor-mediated relaxation of the human detrusor.

PMID- 9777034
TI  - Trypanosoma cruzi antigens down-regulate T lymphocyte proliferation by muscarinic
      cholinergic receptor-dependent release of PGE2.
AB  - Here we demonstrate that T. cruzi antigen molecule SAPA (shed acute phase
      antigen) with neuraminidase-trans sialidase activity triggers down-regulation of
      T lymphocyte proliferation by interacting with T lymphocyte muscarinic
      acetylcholine receptors (mAChR). SAPA attachment to mAChR from Lyt 2.2+ T cells
      resulted in synthesis of cyclic GMP (cGMP) and secretion of PGE2, an
      immunoregulator effector substance. These T suppressor cell signals were blunted
      by atropine and by indomethacin. Cell sorter analysis showed that the interaction
      of SAPA with purified T cells, affected the ratio of L3T4+/Lyt 2.2+ T cells
      increasing the percentage of Lyt 2.2+ T cells, effect that was inhibited by the
      mAChR antagonist, atropine. The interaction between SAPA and mAChR from Lyt 2.2+
      T cells may result, therefore, in the down-regulation of the host immune response
      as consequence of T suppressor/cytotoxic cells activation and PGE2 release as
      they were observed. These results support the theory of an immunosuppressive
      state that contribute to the chronic course of Chagas' disease.

PMID- 9777035
TI  - [Effect of thyroid hormones on the modulation of genetic expression of liver
      cytosolic malic enzyme, in rats poisoned with hexachlorobenzene].
AB  - Hexachlorobenzene (HCB) is a widespread environmental pollutant. Chronic exposure
      of laboratory animals to HCB triggers porphyria, induction of liver microsomal
      enzymes, low levels of T4 reproductive dysfunction's, liver and thyroid tumors.
      Previous findings from our laboratory have shown that HCB increased the activity
      of the liver thyroid-responsive enzymes: malic enzyme (ME), glucose-6-phosphate
      dehydrogenase (G6PD) without any change in the mytochondrial alpha
      glycerophosphate dehydrogenase (alpha-GPD). In this study we have demonstrated
      that HCB treatment increased ME mRNA. We also have investigated if HCB affected:
      a) the thyroid hormone receptor (TR) concentration and binding affinity for its
      ligands, b) specifically the ME gene expression, or other thyroid hormone
      responsive enzymes were affected as well, c) Protein/DNA complex formed on the
      thyroid responsive element (TRE). Livers from female Wistar rats intoxicated with
      HCB (100 mg/100 g b.w.), for 9 and 15 days, were analyzed. Northern blot
      hybridization analysis, have demonstrated that ME mRNA levels increased 4 times
      and 2 times after 9 and 15 days intoxication respectively, without any
      alterations in the mRNA levels of other thyroid hormone responsive enzymes such
      as glyceraldheyde 3- phosphate dehydrogenase, phosphoenolpyruvatecarboxikinase
      and alpha-GPD. These results suggest that HCB affects specifically, ME gene
      expression. Hepatic T3 and T4 levels evaluated by RIA were not affected by HCB.
      Scatchard analyses showed that TR affinity and number of sites were not altered
      after 9 and 15 days of HCB treatment (control, Ka: 1.9 nM, Bmax 3.9 f/mol 100
      micrograms DNA: HCD 9 days Ka: 2.1 nM, Bmax 4.5 fmol/100 micrograms DNA: HCB 15
      days Ka 1.9 nM. Bmax 5.1 fmol/100 micrograms DNA intoxication, neither at 9 nor
      at 15 days. Electrophoresis mobility shift assay showed that HCB did not modify
      nuclear protein extract affinity for the TREs sequence. Our results suggest that
      TR itself was not directly involved in the induction of ME gene expression by
      HCB. Nevertheless TR could interact with other transcription factors in the
      overexpression of ME gene.

PMID- 9777036
TI  - [Effect of the thioctamide in relation to the hexachlorobenzene action].
AB  - Chronic administration of Hexachlorobenzene, with or without the simultaneous
      administration of Tioctamide was assayed. Hexachlorobenzene alone produced the
      characteristic porphyria, detected through an increase of the urinary excretion
      and the hepatic accumulation of porphyrins, as well as by a decrease of the
      Uroporphyrinogen decarboxylase activity. The content of hepatic conjugated dienes
      did not change while those of malondialdehyde increased, although without
      reaching levels of statistical significance. These results would indicate the
      occurrence of an light lipid peroxidation process. The Thioctamide (25 mg/kg body
      weight) produced more noxious effects than protective ones, which were detected
      by a high level of Glutamate piruvate transaminase activity and a decrease of the
      hepatic Uroporphyrinogen decarboxylase activity, at its first step of
      decarboxylation. These results might indicate that: 1) high doses of Thioctamide
      decreases Uroporphyrinogen decarboxylase activity, masking its possible
      protective effect from Hexachlorobenzene's action through free radicals
      production and, 2) Uroporphyrinogen decarboxylase is a more sensitive parameter
      than conjugated dienes or malondialdehyde levels to assay the free radicals in
      vivo Hexachlorobenzene production. In any case, the Thioctamide assayed in lower
      and non toxic doses, perhaps might protect against Hexachlorobenzene's action
      through its free radical scavenger ability.

PMID- 9777037
TI  - [The central cholinergic stimulation in sinoaortic denervation. Effect of
      intracerebroventricular administration of cholinomimetic agents].
AB  - It was decided to made a pharmacological study of the cholinergic participation
      in the sinoaortic denervation experimental model by analyzing the cardiovascular
      effects of several muscarinic agonists and the anticholinesterase neostigmine
      administered either by intravenous via or by the intracerebroventricular via. The
      activity of the enzyme acetylcholinesterase was also evaluated in diverse
      structures of the central nervous system after the intracerebral administration
      of neostigmine. Sinoaortic denervation increases the pressor response to the
      i.c.v. administration of the agonist bethanechol and of the anticholinesterase
      neostigmine but it diminishes the bradycardic effect. However it would not alter
      the cardiovascular responses to the i.v. injection of the agonist oxotremorine
      and to the i c v. administration of the agonist McNeil-A-343. After the i c v.
      administration of neostigmine, the enzymatic activity oscillated among 24%-30% in
      hypothalamic structures and among 42%-52% in the remaining tissues, without
      differences between the rats with sham operation and those with sinoaortic
      denervation. The results suggest that M, muscarinic receptor subtype would not be
      involved in the cardiovascular effects of the central cholinergic stimulation On
      the other hand, it would support the idea of an involvement of muscarinic
      receptors in the observed changes. Because the used route of administration of
      neostigmine, a greater degree of inhibition of the hypothalamic
      acetylcholinesterase is observed, suggesting then that the hypothalamic
      structures could be involved in the cardiovascular effects induced by the
      intracerebral administration of the anticholinesterase.

PMID- 9777038
TI  - [Effect of gonadal hormones on sexual dimorphism in malnutrition substrates].
AB  - The environmental effect on growth and sexual dimorphism is mediated by
      endocrinological dysfunctions. It was shown that malnutrition acts on the
      hypotalamus-pituitary-glandular axis. An experiment was made in Wistar rats to
      determine the effect of some gonadic hormones on the functional components of the
      skull to which sex dimorphism was alterated by a postnatal undernutrition. The
      effects of these hormones in restoring sexual cranial dimorphism was tested. Four
      treatments were applied: control, with food intake ad-libitum; undernutrition
      (50% of the control food intake); undernutrition plus periodic injections of
      testosterone and estradiol to males and females, respectively and sham-operated
      animals, which were injected with oil vehicle only. A radiological longitudinal
      study was performed between 20 and 80 days of postnatal age. The length width and
      height of the neural and facial components were measured on each radiograph. Data
      were processed by ANOVA and Mann-Whitney statistical tests were performed by
      means of the SYSTAT 7.0 statistical package. Results showed that gonadic hormones
      restored the sexual cranial dimorphism by stimulating (testosterone) or
      suppressing (estradiol) the growth of the cranial components.

PMID- 9777039
TI  - Bromocriptine-induced tachycardia in conscious rats: blunted response following
      isoproterenol pretreatment for 5 days.
AB  - Previous studies have shown that tachycardia induced by intravenous injection of
      bromocriptine, which persisted after adrenalectomy, was mediated by central
      dopamine D2 receptor stimulation. Such stimulation could activate central
      sympathetic outflow to the heart. To test this hypothesis, we investigated
      whether pretreatment with isoproterenol, known to induce cardiac beta
      adrenoceptor desensitization, could reduce bromocriptine-induced tachycardia. A 5
      day pretreatment with isoproterenol (5 mg/kg/day) induced a 21% increase in the
      ratio of ventricular dry weight to body weight, compared with saline-pretreated
      rats. In isolated perfused heart preparations from isoproterenol-pretreated rats,
      the isoproterenol-induced increase in left ventricular systolic pressure and
      heart rate was significantly reduced, compared with saline-pretreated rats (the
      isoproterenol concentration producing 50% of the maximal positive inotropic and
      chronotropic responses was increased approximately 5- and 4-fold, respectively).
      In conscious control rats, intravenous injection of bromocriptine (50, 150 and
      250 micrograms/kg) decreased mean aortic pressure and increased heart rate in a
      dose-related manner. Pretreatment with isoproterenol for 5 days reduced
      bromocriptine-induced tachycardia without affecting hypotension. Cardiac
      autonomic tone remained of the same order of magnitude irrespective of whether
      the animal was pretreated with isoproterenol. These results indicate that
      isoproterenol pretreatment reduces bromocriptine-induced tachycardia mainly
      through desensitization of cardiac beta-adrenoceptors rather than via an
      impairment of autonomic regulation of the heart. This supports the hypothesis
      that bromocriptine-induced activation of central dopamine D2 receptors increases
      heart rate via activation of central sympathetic outflow to the heart.

PMID- 9777040
TI  - The public health impact of anxiety disorders: a WHO perspective.
AB  - Anxiety disorders, which may constitute anywhere from one quarter to one half of
      all mental illnesses in the community, are most commonly seen in the primary care
      sector. Despite their significant impact on the functioning of individual
      patients, the plethora of unnecessary medical procedures to which these sufferers
      are subjected, and the large indirect economic burden, these disorders continue
      to be grossly underdiagnosed and undertreated in this sector. Effective
      treatments for anxiety disorders have been available for at least two decades.
      Concerted efforts by the World Health Organization (WHO), the World Psychiatric
      Association and similar organizations are needed to change this picture.

PMID- 9777041
TI  - Comorbidity as a fundamental feature of generalized anxiety disorders: results
      from the National Comorbidity Study (NCS).
AB  - Generalized anxiety disorder (GAD) is a relatively common mental disorder in the
      general population, afflicting approximately 3% of community residents during
      their lifetime. It is not a benign condition, since significantly increased
      disability and dysfunction are found in GAD subjects compared to non-GAD
      subjects. For decades GAD has frequently been observed in the context of other
      mental and substance abuse disorders. Initially the weight of clinical opinion
      indicated that GAD was a residual disease which should only be diagnosed when
      other mental disorders are not present. More recently there has been a growing
      recognition that comorbidity is a fundamental characteristic of the course and
      nature of GAD. In a series of secondary analyses conducted in subjects in the
      National Comorbidity Study database, we found that 8 out of 10 subjects with
      lifetime GAD also had a comorbid mood disorder during their lifetime. We found
      unipolar disorders to be four times more common in GAD than bipolar disorders
      (67% vs. 17%), providing indirect support for the previously reported observation
      that GAD and major depression may share a common genetic diathesis. In addition,
      our analyses support the conclusion that when comorbid mood disorders are present
      in GAD, a significant increase in associated disability and dysfunction is also
      found. Thus this comorbid relationship has important implications for clinical
      course and outcome.

PMID- 9777042
TI  - Generalized anxiety disorder and its comorbidities: disputes at the boundaries.
AB  - This theoretical paper reviews the status of generalized anxiety disorder (GAD)
      and the Axis I and Axis II disorders with which it is often comorbid. Differences
      in comorbidity between the epidemiological and clinical literatures are
      discussed. Special attention is given to panic disorder, the symptoms of which
      are similar to those of GAD. The boundaries of GAD and its relationship to other
      Axis I disorders and to Axis II disorders raise important implications for its
      classification.

PMID- 9777044
TI  - On the one aspect of generalized anxiety.
AB  - Generalized anxiety disorder, considered to be a theoretical and
      psychopathological construct in the Western world, has emerged as an endemic
      daily problem in the post-Soviet republics. The daily uncertainties of life have
      become such a burden for most citizens of these countries that even clinical
      scientists in these countries have largely abandoned the study of this condition.
      Left to the politicians in the leadership of these republics, little alleviation
      has come by way of 'social therapies'. The author of this article, who is
      assigned to the Office of the President of the Republic of Armenia, proposes that
      much is to be gained by both science and society if scientists from western and
      newly independent states jointly study the phenomenology of generalized anxiety
      in these states.

PMID- 9777043
TI  - DSM-IV and beyond: what is generalized anxiety disorder?
AB  - With the advent of DSM-III in the USA (1), a new disorder termed generalized
      anxiety disorder (GAD) was established separately from panic disorder. Because
      GAD was relegated to a residual category, it soon became a confusing diagnosis.
      Although revisions in DSM-III-R (2) removed GAD as a residual category, they also
      complicated the clinical examination necessary to arrive at a GAD diagnosis. With
      the publication of DSM-IV (3), GAD has been further refined in an attempt to
      improve the reliability and discriminability of the disorder. However, it
      continues to be controversial, and a number of issues remain unresolved.

PMID- 9777045
TI  - Psychic and somatic anxiety: worries, somatic symptoms and physiological changes.
AB  - Contrary to self-reports, patients with generalized anxiety disorder exhibit
      increased muscle tension but not autonomic hyperarousal. Under stress they tend
      to react autonomically in a less flexible manner than normal controls. There is
      only a weak relationship, and in some instances a desynchrony, between
      physiological changes and perception of change. The inconsistencies between self
      reports of physiological states and physiological recordings can be explained by
      alterations of body sensations through psychological factors, predominantly
      expectations of and attention to bodily states, that lead to perceptual
      distortions.

PMID- 9777046
TI  - Are sleep disturbances risk factors for anxiety, depressive and addictive
      disorders?
AB  - This paper reviews recent literature which suggests that sleep disturbance in
      members of the general population, whether or not they have ever had a formal
      psychiatric disorder, is a risk factor for the onset of a formal psychiatric
      diagnosis at a later time. Based upon the current literature, the strongest link
      is between subjective insomnia, lasting at least 2 weeks, and the later onset of
      depression. Less well-established data suggest that lifetime reports of at least
      2 weeks of insomnia, hypersomnia, or both hypersomnia and insomnia, are risk
      factors for the later development of depression, anxiety disorders or substance
      abuse. More tentatively, preliminary data suggest that increasing subjective
      sleep disturbance may signal a relapse in remitted depressed patients. Sleep
      disturbances are common manifestations of major depressive and anxiety disorders.
      Therefore, sleep complaints may be among the most robust prodromal symptoms
      reflecting partial depressive or anxiety disorders, which eventually declare
      themselves as full-blown clinical episodes.

PMID- 9777047
TI  - Ethology of anxiety in phylogeny and ontogeny.
AB  - Among animals, fear is a signal of an external danger which can be triggered
      without any learning. Fear is often mediated by the perception of another fear
      issued from a peer, allowing the contagion of the emotion. Ontogeny of animal
      fear can be observed in the natural environment, and it can be experimentally
      manipulated. This suggests the idea that animal fear is an internal signal of a
      danger, and that it develops by imprinting of external objects which categorizes
      the animal's world in a familiar tranquillizing world vs. a strange anxiogenic
      one. In humans, the child's development allows us to observe similar phenomena
      until such time as the child has access to the semantic world, and will
      experience emotions released by gestures and words issued from attachment figures
      or anxiogenic ones.

PMID- 9777049
TI  - Towards a genetics of anxious temperament: from mice to men.
AB  - An enduring question in the study of human personality is 'to what extent and how
      do genetic factors influence such personality constructs as "trait anxiety"?'. We
      selectively survey progress and obstacles in the genetic dissection of fear-like
      behavior, especially as it pertains to more constitutional forms of anxiety or
      anxious temperament. We emphasize the selection of phenotypic dimensions and the
      utility of 'temperament' and personality constructs as mediating variables for
      psychopathology. We summarize studies on the use of mouse models of 'anxious
      temperament' to map genetic loci, and briefly review recent genetic association
      studies of related phenotypes in humans utilizing candidate genes. We suggest
      that further progress in genetic research on 'trait anxiety' disorders may come
      from the following: (i) developing alternate constructs for investigating
      psychiatric illness focusing on dimensional scales, mediating variables and
      premorbid traits; (ii) examining 'at-risk' populations for protective genetic
      factors influencing 'resilience' or loci providing a reduced risk of a given
      trait or disorder; and (iii) utilizing lower animal models as a bridge to dissect
      the genetic factors contributing to related human phenotypes.

PMID- 9777048
TI  - Opponent processes and anxiety: toward a neurophysiological formulation.
AB  - As a general philosophical framework, the author presents a theoretical position
      according to which 'opposition' is at the heart of the workings of the living
      being and the very origins of life. He then deals with 'opposing processes' and
      neural mechanisms which appear to underlie them. The theory rests on the premise
      that a great number of our actions are derived from our emotions, and that the
      coupling of pleasure/suffering controls the expression of our desires. Developed
      in the 1970s, this theory is founded on the observation of dependence phenomena
      (addictions), but its value extends far beyond drugs, to all types of human
      conduct, including sexuality, play, alimentary behaviours, etc. Inconsistent with
      classical theories, it subordinates the act to an affective state. The author
      finally examines the phenomenon of anxiety in the light of these considerations.

PMID- 9777050
TI  - Toward a definition of generalized anxiety disorder as an anxious temperament
      type.
AB  - Generalized anxiety disorder (GAD) is defined as an uncontrollable disposition to
      worry about one's welfare and that of one's immediate kin. Associated
      manifestations include arousal, vigilance, tension, irritability, unrestful sleep
      and gastrointestinal distress. There is growing evidence for the lifelong nature
      of this condition among many of its sufferers. This and other evidence reviewed
      in the present paper provide further support for the thesis that the chronic
      disposition to worry should probably be classified under constitutional or trait
      anxiety. GAD is best considered an exaggeration of a normal personality
      disposition that can be named 'Generalized anxious temperament' (GAT). Despite
      some overlap with anxious-phobic, inhibited and avoidant-sensitive temperaments,
      GAT seems to have a distinct profile with altruistic overtones; on the other
      hand, GAT is less easily distinguished from harm-avoidant and obsessive traits.
      That worrying would increase upon relaxation is not a paradox at all, and is
      understandable in an ethological perspective as subserving the defensive function
      of being vigilant of ever present yet uncertain external dangers--to oneself and
      one's kin--in day-to-day living. GAT can thus be considered as 'altruistic
      anxiety', subserving hypothetically the survival of one's extended phenotype in a
      'kin selection' paradigm. Only when extreme does worrying manifest in a clinical
      context, impairing one's interpersonal life and functioning at work, and
      increasing use of general health care resources. Furthermore, generalized anxiety
      appears to predispose to and is often associated with depression, and a spectrum
      of phobic disorders, as well as alcohol and sedative use. These considerations
      place GAD (and the putative GAT) in the limelight and underscore the need for
      more research into its fundamental characteristics. Towards this aim, a self
      rated GAT measure under development in our center is provided in an appendix to
      this paper.

PMID- 9777051
TI  - Animal models sensitive to anti-anxiety agents.
AB  - Animal models of anxiety serve two primary purposes in psychopharmacological
      research. (i) The pharmacological profile observed in the model provides a basis
      which, depending on its predictive validity, permits an estimation of clinical
      activity. (ii) Insofar as the 'anxiety' occurring in the animal model is
      homologous to human anxiety disorders, it is possible to investigate the
      underlying cellular and molecular mechanisms. The most commonly used laboratory
      procedures for the identification of anxiolytic effects of drugs are described in
      this paper.

PMID- 9777052
TI  - Anxiety and increased aggression as pacemakers of depression.
AB  - The concept of a serotonin (5-HT)-related, anxiety and/or aggression-driven,
      stressor-precipitated depression is formulated and discussed. The serotonergic
      disturbances found in some depressed individuals, particularly those with lowered
      CSF 5-HIAA, are linked to the anxiety and aggression components of the depressive
      syndrome. In this type of depression, called 5-HT-related depression,
      dysregulation of anxiety and/or aggression is hypothesized to be primordial and
      mood-lowering is a derivative phenomenon. In other words, this is a group of
      anxiety/aggression-driven depressions. The author submits that the serotonergic
      impairment in certain types of depression is a trait phenomenon, i.e. it persists
      during remission. This disturbance makes the individual susceptible to
      perturbation of anxiety and aggression regulation. Anxiety and (overt or
      suppressed) anger are core constituents of the stress syndrome. Thus the
      serotonergic disturbance will induce a heightend sensitivity to stressful events,
      i.e. the latter will induce stress phenomena, including anxiety and anger, more
      readily than normal. The latter psychological features induce lowering of mood,
      and thus 'drive' the patient into a full-blown depression. Furthermore, it is
      predicted that anxiolytics and serenics (i.e. anti-aggressive drugs) that act via
      normalization of serotonergic circuits will exert an antidepressant effect in 5
      HT related depression, in addition to their therapeutic actions in anxiety
      disorders and states of increased aggressiveness, respectively. The exact nature
      of the serotonergic impairment in 5-HT-related depression has yet to be
      elucidated.

PMID- 9777053
TI  - Cognition and anxiety: the cognitive effects of anti-anxiety medication.
AB  - There does not appear to be a single hypothesis or theory which can adequately
      explain the aetiology of anxiety, although there is no short-age of contenders.
      Neurochemical, existential, sociogenic, familial, pathological, psychodynamic and
      behavioural explanations have all been offered as putative reasons for the
      psychological disorder, which in its various representations (panic disorder,
      obsessive-compulsive disorder, phobias, post-traumatic stress disorder,
      generalized anxiety disorders, etc.) can affect up to 20% of the population on a
      lifetime basis (1). Notwithstanding the variety of theories and the diversity of
      presentation of anxiety disorders, it would appear that cognitive dysfunction of
      one sort or another is a characteristic feature of anxiety in all its
      manifestations. Indeed, it is possible to argue that a cognitive impairment is
      the primary presenting feature of pathological anxiety, with the characteristic
      syndrome of somatic symptoms as secondary or necessary consequences of such
      cognitive disorder.

PMID- 9777054
TI  - Benzodiazepine dependence and withdrawal: a review of the syndrome and its
      clinical management.
AB  - The treatment of anxiety has evolved through various phases. Currently, there is
      a growing recognition that anxiety disorders are frequently chronic and/or
      recurrent. There is also less optimism than a decade ago that benzodiazepines
      will be replaced by alternative agents that are not active at the benzodiazepine
      receptor. Consequently, the understanding and management of benzodiazepine
      dependence and withdrawal continue to be of some clinical importance. This
      article briefly reviews the withdrawal syndrome and the pharmacological and
      patient variables that contribute to it. It then summarizes the various
      approaches to managing benzodiazepine dependence and withdrawal.

PMID- 9777055
TI  - Recent clinical trials of hydroxyzine in generalized anxiety disorder.
AB  - Numerous clinical trials in the 1960s and 1970s have attested to the anxiolytic
      efficacy of hydroxyzine and its beneficial effect on sleep, as well as in
      reducing stress and anxiety associated with coronary disease. Experience with
      hydroxyzine has also shown a lack of organ toxicity and an absence of dependency.
      Recent controlled clinical trials with hydroxyzine have confirmed its efficacy
      (at a fixed dose of 50 mg) in generalized anxiety disorder--superiority over
      placebo on all anxiety measures from the first week with early target symptoms
      which are grouped in a cognitive component of anxiety. Efficacy was maintained
      throughout the 4 weeks of treatment and after abrupt discontinuation. In another
      controlled trial vs. lorazepam, hydroxyzine demonstrated greater and more rapid
      cognitive improvement.

PMID- 9777056
TI  - The nature and duration of treatment for GAD.
AB  - It is becoming increasingly evident that GAD is a chronic condition with repeated
      acute-on-chronic episodes. Treatment in the short term relies on the
      benzodiazepines, which are rapid in action, providing substantial symptomatic
      relief with a low incidence of side-effects and low toxicity in overdose. The
      risk of more serious unwanted effects in the long term, including some risk of
      physical dependence, has led to a move towards alternative treatments both
      pharmacological and psychotherapeutic. Antidepressants are being used on a long
      term basis, but data are sparse to confirm their efficacy in GAD. Anxiety
      management and cognitive-behavioural techniques are rivalling pharmacotherapy in
      popularity. None the less, research seeking optimal ways of combining therapies
      remains an urgent priority.

PMID- 9777057
TI  - The ramifications of regulatory reform.
AB  - This article examines the regulatory reform proposals for the health care
      workforce recently proposed by politicians and members of the Pew Health
      Professions Commission. These proposals attempt to address issues related to
      state practice acts, competence, advanced practice, "boundaryless" practice, the
      disciplinary process, consumerism, and umbrella legislation. Questions are
      presented for each issue to guide practitioners when deliberating about possible
      actions professional organizations can take in proposing legislation at the state
      level. Various external forces shape each issue and lead to the need to seek such
      regulatory reform as improving disciplinary processes and activity, assessing
      competence beyond the entry level, and increasing involvement of consumers.
      However, there are risks associated with any proposed regulatory reform,
      particularly if one realizes the potential financial costs associated with
      competency assessment and advanced-practice regulation. We must also carefully
      examine any reform proposals that advocate title protection and the licensing of
      invasive procedures in place of licensing professionals. The fact remains that
      the impact on quality of care and long-term cost-effectiveness from the
      unrestricted use of less qualified professionals and unlicensed aide-level
      personnel to provide skilled services has not been adequately determined.

PMID- 9777058
TI  - Continuing competence in the health professions.
AB  - The health professions are confronted with external pressures to assure the
      public of the continuing competence of health care providers and internal
      pressures for self-regulation. This article describes the forces driving
      continuing competence, the difficulty defining the scope of professional
      competencies for experienced practitioners, the difficulty creating valid
      measures to evaluate continuing competence, and the need for shared
      responsibility and collaboration among regulatory boards, professional
      associations, and specialty certification programs. The article presents findings
      from the Study of Professions, which was based on literature review, document
      review, and telephone interviews with key informants from 13 regulated health
      professions.

PMID- 9777059
TI  - Evolving competence in the practitioner role.
AB  - This article discusses competence from the viewpoint of the practitioner role.
      Concepts from two documents published by the American Occupational Therapy
      Association--Occupational Therapy Roles and Developing, Maintaining, and Updating
      Competency in Occupational Therapy: A Guide to Self-Appraisal--are integrated
      within the discussion. Discussed in this article are factors that affect
      competence, the interrelationship of competence and practice, and personal
      responsibility for competence; ways in which competence may be challenged during
      the practitioner's career; common misconceptions about competence; and attitudes
      and actions in which the competent practitioner engages. Competence is described
      as a complex and evolving set of abilities that develops throughout the
      practitioner's career.

PMID- 9777060
TI  - The national occupational therapy practice analysis: findings and implications
      for competence.
AB  - OBJECTIVE: This article reports some of the findings from a national study of
      occupational therapy practice conducted by the National Board for Certification
      in Occupational Therapy (NBCOT) as part of its fiduciary responsibility to ensure
      that its entry-level certification examination is formulated on the basis of
      current practice. METHOD: The NBCOT developed a survey with input from
      approximately 200 occupational therapy leaders and then used it to solicit
      information about current practice from 4,000 occupational therapists and 3,000
      occupational therapy assistants. The sample included geographical location,
      experience level, and practice area distributions. RESULTS: Approximately 50% of
      the sample responded to the survey. Data indicate similarities and differences in
      occupational therapist and occupational therapy assistant practice (e.g.,
      occupational therapists spend more time conducting evaluations, planning
      interventions, and supervising, whereas occupational therapy assistants spend
      more time providing interventions), an increased emphasis on population-based
      services (e.g., serving a business or industry rather than an individual worker),
      and an emphasis on occupation as a core knowledge base for practice. From a
      continuing competency perspective, the data can be useful to the profession; we
      can plan continuing education to address topics that practitioners have indicated
      are critical to their practice. CONCLUSION: The findings will be useful for
      revising the entry-level certification examination and may guide thinking about
      the parameters of continuing competence because the responses represent a cross
      section of the profession.

PMID- 9777062
TI  - Accountability and competence: occupational therapy practitioner perceptions.
AB  - OBJECTIVE: Occupational therapy practitioners must meet ever-increasing
      accountability demands in all service delivery environments. Accountability is
      made possible through the ongoing development of continued competence throughout
      a practitioner's career. Behaviors that demonstrate accountability and reflect
      competence include commitment, leadership, and professional knowledge. This
      article discusses issues related to accountability and competence, presents
      findings from focus group discussions with occupational therapy practitioners
      regarding professional competence, and identifies actions that will bring about
      greater understanding of this topic. METHOD: Thirty-nine randomly selected
      occupational therapy practitioners attended one of two focus groups. Participants
      responded to a structured discussion guide, including questions addressing the
      definition, process for sustaining, and outcomes of continued competence.
      RESULTS: Several themes emerged from these discussions. Views about what
      constitutes and contributes to continued competence in occupational therapy were
      diverse, and perceptions of occupational therapy "practice" were broad.
      Participants believed that the "outcomes" of a practitioner's continued
      competence were best defined as autonomy in executing the occupational therapy
      process. CONCLUSIONS: Findings offer potential language to articulate competence
      in occupational therapy and facilitate a discipline-wide conversation. The
      findings likewise challenge practitioners to assume new professional behaviors
      that require both personal and interpersonal skills. Such behaviors are critical
      to demonstrating accountability and competence.

PMID- 9777061
TI  - Transitional portfolios: orchestrating our professional competence.
AB  - Reflective professional development results from thoughtful planning of goals and
      meeting learning objectives. With rapid changes in health care resulting in major
      reevaluation and even modification of the role and functions of an occupational
      therapy practitioner, producing a historical record of competencies in order to
      learn from one's own experience and to plan for change is essential. A new use of
      the portfolio is presented to show that a portfolio can be more than the typical
      repository of completed projects. The transitional portfolio is introduced as a
      tool for one to self-direct professional development through thoughtful
      engagement with artifacts created during one's career in relationship to
      professional goals and desired roles. The transitional portfolio process is
      holistic, flexible, and reflective. It can serve as a way to document accumulated
      knowledge and skill acquisition as well as facilitate thoughtful, planned
      reflection on one's career development in occupational therapy. This article
      describes the use of transitional portfolios to connect professional development
      learning experiences, accomplishments, and future opportunities for occupational
      therapy practitioners.

PMID- 9777063
TI  - Management competencies required of administrative and clinical practitioners in
      the new millennium.
AB  - Changes in the health care environment necessitate revisiting management-related
      competencies for both clinical and administrative practitioners. Major changes
      include the shift from recruitment to reengineering, direct service to multiple
      service models, department to program management, professional standards to
      market-driven standards, and single-system to multisystem management. Important
      competencies include the ability to identify and implement flexible staffing, to
      use communication technologies to support staff members across multiple sites, to
      understand of the business of health care, and to create innovative service
      delivery models consistent with the core values of the profession.

PMID- 9777064
TI  - Competence in scientific inquiry and research.
AB  - The survival and expansion of the profession of occupational therapy depends on
      its ability to respond to continually changing environments. One of the most
      current and critical factors in this adaptation is the capacity of therapists to
      achieve competence in scientific inquiry and research. Competence in the role of
      researcher is necessary because it contributes to the development of the
      individual therapist, the profession, and the organization within which the
      therapist functions. The aim of this article is to review and elaborate on the
      competencies associated with the role of researcher and to propose a
      reconceptualization of the knowledge, skills, and attitudes that shape competence
      in scientific inquiry.

PMID- 9777065
TI  - The competent scholar.
AB  - Scholars in occupational therapy are responsible for ensuring that the
      profession's body of knowledge is so formulated that it provides the foundation
      for carrying out the work of the profession effectively, compassionately, and
      ethically. This article delineates the knowledge, skills, and typical personal
      attributes of competent scholars. Some suggestions are offered about how the
      occupational therapy profession might increase its number of competent scholars.

PMID- 9777066
TI  - Competence and the occupational therapy entrepreneur.
AB  - That which constitutes competence in an occupational therapy entrepreneur is not
      well delineated, even though the role of entrepreneur requires that such a person
      possess a particular set of knowledge and skills in order to be competent. The
      question of competence in an occupational therapy entrepreneur is increasingly
      important because the number of practitioners assuming this role has grown in
      recent times. Indeed, a connection exists between the competence of occupational
      therapy entrepreneurs and the future stature of the profession. Still, the issue
      remains: How will occupational therapy entrepreneurs be judged competent? Peer
      evaluation is one possibility, but the ultimate measure will be marketplace
      success.

PMID- 9777067
TI  - Errors in statistics could lead to misinterpretation.

PMID- 9777068
TI  - Focus on occupation is much needed.

PMID- 9777069
TI  - Intensivists for the intensive care unit--do they make a difference?

PMID- 9777070
TI  - Impact on quality of patient care and procedure use in the medical intensive care
      unit (MICU) following reorganisation.
AB  - We conducted this retrospective, cohort study to evaluate the quality of patient
      care and procedure use in the medical care unit (MICU) following reorganisation
      and staffing by an intensivist. Consecutive admissions to an adult MICU in a
      university affiliated hospital during two 3-month periods, August to October 1993
      (Period 1, n = 112) and January to March 1994 (Period 2, n = 127) were analysed.
      In Period 1, the MICU was run under the open system in which patient care was
      provided by the individual attending physicians. In Period 2, a resident MICU
      team led by a trained intensivist took over the medical care from the primary
      physicians when the patients were admitted to the MICU. The intensivist also
      vetted MICU admission and decided on MICU discharge. In addition, there was a
      resident respiratory therapist to attend to ventilatory care during office hours.
      After office hours, the care of the MICU was delegated to the on-call team on a
      rotational basis among the medical departments. This was the semi-closed ICU
      model. The patients in the two periods were similar with respect to age, sex,
      race, source of admission and APACHE II scores. There was improvement in the
      median ICU length of stay for survivors from 3 days in Period 1, to 2 days in
      Period 2 (P = 0.0114). The relative risk of ICU death in Period 1 compared to
      Period 2 was 1.23 (P = 0.286). There was no significant difference in the use of
      peritoneal dialysis (5.4% versus 6.3%) and mechanical ventilation (55.4% versus
      49.6%). However, utilisation of intra-arterial lines and pulmonary artery
      catheters increased from 0% in both Periods 1 and 2 to 23.6% and 5.5%,
      respectively. Reorganisation of the MICU in Period 2 resulted in reduced length
      of MICU stay for survivors. Hence, we believe that coverage by a dedicated ICU
      team and active respiratory care by a respiratory therapist during office hours
      were beneficial for the care of the critically ill. There was also a noticeable
      increase in the use of invasive monitoring.

PMID- 9777071
TI  - Audit of 2431 admissions to the Surgical Intensive Care Unit, Singapore General
      Hospital.
AB  - A prospective analysis of 2431 patients admitted to the Surgical Intensive Care
      Unit (SICU) of Singapore General Hospital was conducted between January 1994 and
      June 1997. All patients were followed up until hospital discharge. This ongoing
      project serves as both audit and quality assurance in the SICU. The mean APACHE
      II score of patients was 12.67 +/- 8.36 and the mean age was 59.17 +/- 17.82
      years. There were 157 re-admissions, giving a re-admission rate of 6.46%.
      Mortality rate for re-admitted patients was 48.4%. One hundred and four (4%)
      patients stayed in the SICU for more than 2 weeks. Thirty (29%) died before the
      SICU discharge. SICU mortality was 9.46%, hospital mortality was 10.86% and
      standardised mortality ratio was 1.95. Computerised tools that analyse ICU
      utilisation patterns and outcomes have the potential to better target resources
      and so lower hospital costs, reducing futile medical care by selecting patients
      for appropriate expensive ICU care.

PMID- 9777072
TI  - APACHE II and SAPS II are poorly calibrated in a Hong Kong intensive care unit.
AB  - This study seeks to determine if the Acute Physiology and Chronic Health
      Evaluation II (APACHE II) and the new Simplified Acute Physiology Score (SAPS II)
      model predictions are well calibrated in our adult Intensive Care Unit (ICU)
      patient population. 1064 successive ICU discharges were enrolled with 222 deaths
      at hospital discharge. APACHE II predicted 287.44 deaths, thus giving an APACHE
      II standardised mortality ratio (SMR) of 0.77 (95% confidence interval +/- 0.07).
      SAPS II predicted 269.59 deaths, giving a SAPS II SMR of 0.82 (95% confidence
      interval +/- 0.07). The Hosmer-Lemeshow goodness-of-fit C statistic was 43.96 for
      APACHE II and 49.06 for SAPS II (P < 0.001 for both, inferring significant
      departures from the null hypotheses of good calibration). The area under the
      Receiver Operating Characteristic plot for SAPS II risk of death was 0.87 (95%
      confidence interval +/- 0.028) while that for APACHE II risk of death was 0.88
      (95% confidence interval +/- 0.026). Although the APACHE II and SAPS II models
      provide good discriminatory performance this study finds the APACHE II and SAPS
      II models to be poorly calibrated in that they over-predict mortality in our ICU
      population.

PMID- 9777073
TI  - Survival after cardiopulmonary resuscitation in the general wards--the results of
      a dedicated "code" team.
AB  - We describe our experience with a dedicated cardiopulmonary resuscitation team
      over 13 months for adults out-of-intensive care unit cardiopulmonary arrests.
      There were 137 recorded arrests with the majority (69%) happening "out-of-office
      hours". The ages of patients ranged from 27 to 95 years, with 42% of patients >
      or = 70 years old. Spontaneous circulation was established in 38% with transfers
      to the intensive care unit. However, only 27% of these patients eventually
      survived to hospital discharge. Thus, there was an overall 10% hospital survival
      for all adult arrests in the general wards. Those that had return of spontaneous
      circulation were significantly younger than the nonsurvivors. Patients less than
      70 years old had a higher hospital survival rate than those > or = 70 years old
      (16.5% vs 8.6%, chi 2 < 0.0001).

PMID- 9777074
TI  - Predictors of long-term outcome in severe head injury.
AB  - Severe head injury is associated with significant morbidity and mortality. We
      conducted a retrospective study to assess the long-term outcome of these patients
      using the Glasgow Outcome Score (GOS) and evaluate the variables that might
      predict outcome. Data were collected from all post-traumatic neurosurgical
      patients with severe head injury (Glasgow Coma Scale 8 or less) admitted to the
      Surgical Intensive Care Unit over a 29-month period. The long-term outcome was
      assessed one year after the injury by a telephone interview or a review of the
      hospital records. Seventy patients satisfied the criteria for the study. The male
      to female ratio was 9:1. The mean age of the patients was 37 (range 17 to 84)
      years. The overall mortality was 50%. Patients with a poor outcome (defined as
      GOS scores of 1 to 3) had a significantly higher mean age, higher Acute
      Physiology and Chronic Health Evaluation (APACHE) II score and a lower Glasgow
      Coma Scale than those with a good outcome (GOS 4 to 5). The APACHE II score
      correlated better with outcome than the Glasgow Coma Scale or age. The APACHE II
      score may be used to prognosticate the long-term outcome in severe head injury.

PMID- 9777076
TI  - Diabetes insipidus in neurosurgical patients.
AB  - Diabetes insipidus (DI) is an uncommon but important complication in the
      neurosurgical population. This retrospective study aimed to determine the
      incidence, profile and outcome of patients admitted to an 18-bedded neurosurgical
      intensive care unit who developed DI. The overall incidence was 3.7% (29/792
      admissions). Aetiologies included subarachnoid haemorrhage (12/29), severe head
      injury (11/29), post-surgical excision of craniopharyngioma or pituitary adenoma
      (5/29) and acute haemorrhagic stroke (1/29). All patients were treated with a
      regime of fluid replacement, electrolyte correction, parenteral or intranasal
      desmopressin (DDAVP), or parenteral pitressin. Overall mortality was 72.4%. There
      were no deaths in the patients who underwent excision of tumours. Complications
      included acute pulmonary oedema, hypernatremia and hypokalaemia. The development
      of DI was found to be associated with impending brain death and mortality in the
      majority of patients with subarachnoid haemorrhage and severe head injury.
      However, careful diagnosis and management of DI after hypothalamo
      neurohypophyseal surgery did not result in any permanent neurological sequelae.

PMID- 9777075
TI  - Outcome of patients with traumatic brain injury managed on a standardised head
      injury protocol.
AB  - A standardised protocol in the management of severe head injury in our hospital
      enables pre-determined critical care-paths and consistent treatment regimes to be
      instituted. In Singapore there has been no previously reported data on the
      outcome of severely head injured patients. Over a 6-month period, 48 consecutive
      patients who were enrolled in our severe head injury protocol were prospectively
      studied. In addition to demographic and outcome data, physiologic measurements
      obtained from a computerised patient information system (Carevue Hewlett-Packard
      9000) were analysed to determine the mean cerebral perfusion pressure (CPP) and
      intracranial pressure (ICP) achieved throughout the protocol period. Median
      Glasgow Coma Score for all patients on admission to the protocol was 6 (range 4
      to 8). The mean age was 34.46 +/- 15.03 years with a male to female ratio of
      43:5. The average duration of treatment on the protocol was 110.73 hours. Initial
      ICP measured was 25.5 +/- 19.68 mmHg. Outcome was measured at 6 months post
      injury using the Glasgow Outcome Score. Favourable outcome (GOS 4-5) was seen in
      29 of 48 patients (60.4%) while 12 out of 48 (25%) had an unfavourable outcome.
      There was a mortality of 14.6% (7 of 48 patients). Patients who survived had a
      higher mean CPP (P = 0.00005), a lower initial ICP and a mean ICP (P = 0.007 and
      0.0009). The use of a protocol with standardised treatment goals in the
      management of traumatic brain injury allows for the optimal use of limited
      resources and provides consistency in treatment. Good outcome is related to early
      aggressive resuscitation to prevent hypotension and hypoxia, prompt evacuation of
      surgical mass lesions and the maintenance of an adequate cerebral perfusion
      pressure. Our results are comparable with that reported in other established
      neurotrauma systems.

PMID- 9777077
TI  - A retrospective study of near-drowning victims admitted to the intensive care
      unit.
AB  - A retrospective study was conducted to evaluate the outcome of near-drowning
      patients admitted to the intensive care unit (ICU) comparing seawater and
      freshwater drownings. A chart review was used to identify near-drowning patients
      admitted to ICU from 1 April 1989 to 1 May 1996 for biodata, physiological data
      and outcome. Seventeen near-drowning patients were admitted to ICU over a period
      of nearly 7 years. There were 3 deaths (17.6%) and 8 patients (47%) required
      cardiopulmonary resuscitation. Freshwater near-drowning occurred in 8 patients
      and saltwater near-drowning occurred in 9 patients. Nearly all (94%) the patients
      had a PaO2/FiO2 ratio < 300 mm Hg. Pulmonary oedema was present on the chest
      radiographs of all patients. Mechanical ventilation was required for 8 patients
      (47%), and nearly all (94%) received prophylactic antibiotics. None of the
      patients developed pneumonia. Serum electrolytes and haemoglobin concentration
      were not grossly abnormal although, those with saltwater near-drowning had a
      significantly higher level of haemoglobin, sodium and urea compared to those with
      freshwater near-drowning. Patients that survived to hospital discharge had full
      neurological recovery and stayed an average of 4.5 days. We concluded that near
      drowning victims that survive to be admitted to ICU have significant oxygenation
      defect with nearly half requiring ventilatory support. Mortality is appreciable,
      but those that survive to hospital discharge had full neurological recovery.

PMID- 9777078
TI  - Patients admitted to an intensive care unit for poisoning.
AB  - This paper presents our experience with patients admitted for poisoning to the
      adult medical intensive care unit (MICU), Tan Tock Seng Hospital, from 1 January
      1993 to 31 December 1995. Case records of 50 consecutive patients admitted to the
      MICU for management of poisoning were retrospectively analysed for epidemiologic
      data and intensive care interventions. There were equal proportions of male and
      female patients. The majority (76%) were in the economically productive age group
      of 21 to 60 years old. Most patients (24 out of 50) stayed for 1 day only. The
      most common drugs involved were organophosphates and carbamates (16 occurrences),
      benzodiazepines (12 occurrences), tricyclic antidepressants (12 occurrences), and
      phenothiazines (8 occurrences). About a third involved multiple-agent poisoning;
      this was significantly more common in males. Fifty-eight per cent of patients had
      suicidal intent. There were 4 deaths (8%) during this period; 3 of these were due
      to poisoning by organophosphates and carbamates. Seventeen patients were
      ventilated, 2 underwent peritoneal dialysis, and 1 underwent forced diuresis.

PMID- 9777079
TI  - Malaria requiring intensive care.
AB  - We studied 24 consecutive adult patients with malaria who required intensive care
      between 1 January 1994 and 31 December 1997. This was out of a total of 256
      patients hospitalised at the Singapore General Hospital with malaria during these
      4 years. Our aim was to characterise the type and severity, clinical features,
      complications, treatment and outcome of adult patients with malaria who required
      intensive care. In addition, we compared the actual and predicted mortality based
      on the Acute Physiology and Chronic Health Evaluation II (APACHE II) score. The
      travel history, prophylaxis, duration of fever before receiving treatment, type
      of malaria and severity, clinical data, complications, APACHE II score, treatment
      and outcome were analysed. Most cases were imported by locals travelling overseas
      or foreigners infected with the parasite elsewhere. Four patients had vivax
      malaria and 20 patients had severe falciparum malaria. All but 1 patient received
      transfusion with blood products and 6 patients with severe falciparum malaria had
      exchange transfusions. Complications were restricted to infection with P.
      falciparum: 9 patients required acute dialysis and 8 required mechanical
      ventilation. Three patients died giving a mortality of 15% for severe falciparum
      malaria. The overall mortality of patients with malaria was 1.2%. The mortality
      of patients with malaria requiring intensive care was 12.5% as compared with a
      predicted mortality of 18.7% based on the APACHE II prognostication system.

PMID- 9777080
TI  - Use of central venous lines in paediatrics--a local experience.
AB  - Central venous catheters are widely used in the care of critically ill patients.
      This paper reviews our experience with central lines in paediatric patients
      requiring intensive care, between the period August 1994 and August 1995. A total
      of 57 insertions were performed in 40 patients, all less than 12 years of age. We
      found that the most common indication for catheter use was nutritional support
      (40%). The overall complication rate was 58%. Catheter-related infection was the
      most serious problem, occurring in 32% of all insertions. Coagulase-negative
      Staphylococcus aureus was the organism most frequently isolated. Maintenance
      problems affected 17 of our catheters in which 9 were blocked. Both infected and
      blocked catheters were promptly removed. We had 3 cases of perforation and 2
      cases of thrombosis. There were no deaths directly attributed to catheter use.
      Recommendations made include: 1) staff education and new guidelines for catheter
      care, 2) use of bacteria filters, 3) careful prospective monitoring of catheter
      infection rate, 4) heparinisation when infusion rate less than 2 ml/h, 5)
      eliminate use of stiff polyethylene catheters and 6) routine confirmatory X-ray
      or waveform monitoring before catheter use, if possible. We concluded that
      central venous catheterisations greatly facilitated the management of our
      patients. However, one must bear in mind that the use of such catheters is
      associated with problems which must be recognised early and promptly treated and,
      if possible, prevented with safe practice.

PMID- 9777081
TI  - Five paediatric case reports of the use of adenosine in supraventricular
      tachycardia.
AB  - The efficacy, safety and diagnostic usefulness of adenosine in the treatment of
      supraventricular tachycardia in children were prospectively studied over a 2-year
      period. Only patients who were stable and without hypotension were included.
      Adenosine was given at a dose of 0.1 mg/kg and increased to 0.2 mg/kg for the
      second and third doses if there was no response. Adenosine was used on 5
      occasions in 5 patients. Adenosine was found to be effective in terminating
      supraventricular tachycardia in all 5 patients; 4 responded to a dose of 0.2
      mg/kg while 1 responded to 0.1 mg/kg. Wolff-Parkinson White Syndrome was detected
      in 2 patients after termination of supraventricular tachycardia. Transient
      hypotension was noted in 1 patient lasting 45 seconds with no haemodynamic
      consequences. Two patients had transient ventricular ectopics lasting 3 to 5
      seconds. One out of 3 patients who were old enough to report side-effects,
      experienced chest discomfort and dizziness lasting 5 seconds. All side-effects
      were transient and mild. We concluded that adenosine is effective and safe in
      terminating supraventricular tachycardia in children after vagal manoeuvres have
      failed.

PMID- 9777082
TI  - A retrospective study of infants with severe persistent pulmonary hypertension
      (PPHN) managed without extracorporeal membrane oxygenation (ECMO).
AB  - We studied 13 consecutive infants admitted to our Neonatal Intensive Care Unit
      over 37 months from 1 June 1994 to 30 June 1997, who were diagnosed with severe
      persistent pulmonary hypertension (PPHN) meeting extracorporeal membrane
      oxygenation (ECMO) criteria as defined by Bartlett and/or Short. They were
      managed with conservative ventilation strategy, with emphasis on the use of
      moderate ventilatory pressures whilst avoiding paralysis. Peak inspiratory
      pressure (PIP) on intermittent mandatory ventilation was adjusted according to
      adequate chest excursion. High PIP was avoided. Two main ventilatory techniques
      were used: 1) low ventilatory rate < or = 40/min, PIP 20 to 30 cmH2O, inspiratory
      time (IT) 0.5 seconds, positive end-expiratory pressure (PEEP) 5 cmH2O, and 2)
      high ventilatory rate 100/min, PEEP 0 cmH2O, IT 0.3 seconds. The aim was to keep
      preductal PaO2 > or = 50 mmHg. We did not sought to achieve alkalotic pH or low
      PaCO2. When PIP requirements exceeded 30 to 35 cmH2O, the use of an alternative
      rescue therapy such as pulmonary vasodilator, high frequency ventilation and/or
      surfactant were considered. Only 1 infant died of PPHN. Low mortality due to PPHN
      can be achieved using this strategy. There is a need for a randomised controlled
      trial to compare this strategy with other alternative treatment strategies.

PMID- 9777083
TI  - Caudal morphine in paediatric patients: a comparison of two different doses in
      children after major urogenital surgery.
AB  - We compared the duration of postoperative analgesia and the occurrence of side
      effects of two different doses of caudal morphine in children undergoing major
      urogenital surgery. Fifty-two children aged between 1 and 12 years were randomly
      selected to receive caudal morphine, either 25 micrograms.kg-1 (Group A) or 50
      micrograms.kg-1 (Group B) with 0.5 ml kg-1 of 0.25% plain bupivacaine immediately
      before surgery. They were monitored for 24 hours in a high dependency area for
      known complications of epidural morphine. There was no significant difference in
      postoperative analgesia between the two doses of caudal morphine. Clinically
      significant respiratory depression or sedation was not detected in either group.
      The occurrence of vomiting and pruritus was similar in both groups. Urinary
      retention was not recorded as all children had an indwelling catheter as required
      by the surgical procedure. We concluded that 25 micrograms.kg-1 of caudal
      morphine is as effective as 50 micrograms.kg-1 for providing postoperative
      analgesia in children undergoing urogenital surgery.

PMID- 9777084
TI  - Critical care--the worldwide perspective.
AB  - The development of the specialty of critical care and the intensivist is outlined
      and the data that favours critically ill patients being cared for by intensivists
      are reviewed. The future challenges for intensive and critical care are dealing
      with the new ethical dilemmas raised by intensive care, providing appropriate
      intensive care in both developed and developing countries and applying the
      principles of evidence-based medicine to intensive therapy.

PMID- 9777085
TI  - Critical care medicine in the Western Pacific region.
AB  - The Western Pacific region has seen rapid recent economic development but
      variation in the provision and organisation of intensive care units (ICUs)
      between different countries remains. While Japan, Australia, New Zealand,
      Singapore, Taiwan, Korea and Hong Kong have well developed intensive care
      facilities, in other countries the more limited funding for healthcare can be
      reflected by differential availability of modern medical technology between the
      public and private sectors. Other factors important to intensive care include
      physician training, availability of other staff and whether intensive care is
      delivered in "open" or "closed" units. At present only Japan, Hong Kong, the
      Philippines, Australia and New Zealand have a postgraduate examination in
      intensive care leading to recognition as an intensive care physician. In Japan,
      Australia, New Zealand and Indonesia each hospital usually has a single
      multidisciplinary (medical-surgical) ICU, whereas most other Western Pacific
      countries have divided medical and surgical units. In Japan, Australia, New
      Zealand, Hong Kong, Taiwan and Thailand, the larger ICUs are usually staffed by
      full-time intensivists. Future development of intensive care in the region will
      parallel economic development. In most countries increasing patient expectations,
      ageing populations and "Western" diseases will increase demand for intensive care
      services. Only a few countries currently have recognised programmes of training
      and certification in intensive care but as more adopt this process it should lead
      to a clearer recognition and acceptance of the role of the intensivist.

PMID- 9777086
TI  - Controlled observations in critical care medicine: the therapeutic trial.
AB  - The practice of critical care medicine revolves around the monitoring of patients
      to identify acute physiologic deterioration and the titration of therapies aimed
      at supporting internal homeostasis. Central to this practice is the evaluation of
      therapies or stresses designed to assess homeostatic reserve and to uncover
      pathologic processes. Both the cardiovascular and respiratory systems have
      received particular attention because of the ease with which specific
      haemodynamic and respiratory parameters can be measured, the ability to modulate
      their status with therapies, and the intimacy of both cardiovascular and
      respiratory status to overall homeostasis. These forms of assessment are referred
      to as clinical trials, and if performed in a rigorous fashion are referred to as
      controlled clinical trials. Clinical trials form much of the basis for titration
      of therapy, wherein a specific therapy is adjusted so as to optimise its
      effectiveness in an individual. Titration is typically done once a diagnosis has
      already been made or a treatment identified, such as with the titration of
      antihypertensive therapy in either hospital or outpatient setting. This review
      will focus on the exploratory aspect of clinical trials wherein a specific
      manoeuvre is performed to determine either the aetiology or severity of a
      pathophysiologic problem.

PMID- 9777087
TI  - Severity scoring systems in the modern intensive care unit.
AB  - In recent years, several factors have led to increasing focus on the meaning of
      appropriateness of care and clinical performance in the intensive care unit
      (ICU). The emergence of new and expensive treatment modalities, a deeper
      reflection on what constitutes a desirable outcome, increasing financial pressure
      from cost containment efforts, and new attitudes regarding end-of-life decisions
      are reshaping the delivery of intensive care worldwide. This quest for a measure
      of ICU performance has led to the development of severity adjustment systems that
      will allow standardised comparisons of outcome and resource use across ICUs.
      These systems, for many years used only in the research setting, have evolved to
      become sophisticated, computer-based decision-support tools, in some instances
      commercially developed, and capable of predicting a diverse set of outcomes.
      Their application has broadened to include ICU performance assessment, individual
      patient decision-making, and pre- and post-hoc risk stratification in randomised
      trials. In this paper, we review the popular scoring systems currently in use;
      design issues in the development and evaluation of new scoring systems; current
      applications of scoring systems; and future directions.

PMID- 9777088
TI  - The oxygen delivery debate--a review.
AB  - Tissue hypoxia is an important cause for the development of multisystem organ
      failure in the critically ill. Achieving adequate haemodynamic support of oxygen
      demand is the mainstay of treatment in these patients. Controversies regarding
      therapeutic end-points do exist but in general maintaining oxygen delivery by
      ensuring adequate cardiac output, oxygen saturation and haemoglobin is important
      in the critically ill.

PMID- 9777089
TI  - Ventilatory strategies for acute respiratory distress syndrome.
AB  - Acute respiratory distress syndrome (ARDS) is a severe condition that has a high
      mortality. Mechanical ventilation is required and concepts have evolved over the
      last few decades as to the methods and principles guiding such ventilatory
      support. In particular, volutrauma as a feature of ventilator-associated lung
      injury has been well documented, leading to pressure-limited strategies with
      consequent permissive hypercapnia. Such an approach is in direct contrast to
      traditional ventilatory teaching of high tidal volumes and normal PaCO2. Current
      strategies therefore emphasis lower tidal volumes, adequate positive end
      expiratory pressure (PEEP), minimum FiO2, and the use of pressure-control modes
      (plus or minus inverse-ratio ventilation). Hypercapnia is allowed to develop, and
      adjunctive methods are employed to improve oxygenation in order to minimise the
      "pressure-cost" of maintaining adequate oxygenation. With such an approach,
      overall mortality is reported to be around 40%.

PMID- 9777090
TI  - Nitric oxide in septic shock: directions for future therapy?
AB  - Septic shock is a major cause of death among patients in intensive care units. It
      has a mortality rate of 20% to 80%. The clinical syndrome of septic shock is
      characterised by hypotension, hyporesponsiveness to vasoconstrictors and volume
      depletion which will then lead to multiorgan dysfunction and death. Except for
      surgical and supportive care, no specific therapy is known. Recently interest has
      been focused on the role of nitric oxide (NO) in septic shock. Large amounts of
      NO released by the endothelium and vascular smooth muscle cells lead to profound
      vasodilation and hyporesponsiveness to vasoconstrictors. The cytotoxic effect of
      NO could also cause tissue injury and organ failure. Inhibition of NO synthase,
      the enzyme responsible for NO production, has been proposed as a new therapy for
      septic shock. However, experimental reports have provided conflicting results,
      demonstrating both beneficial and detrimental effects. A brief review of the role
      of NO in septic shock and the possible use of NO synthase inhibitors as potential
      therapeutic agents is presented here.

PMID- 9777091
TI  - Contributions of respiratory care practitioners to intensive care: a review.
AB  - Through the years, the professional practice of respiratory care has continually
      evolved to include management of critically ill patients. Although the functions
      and duties of respiratory care practitioners (RCPs) in this setting may vary
      across different institutions, it is widely recognised throughout the United
      States that RCPs contribute importantly to intensive care unit (ICU) outcomes.
      The American Association for Respiratory Care (AARC) has painstakingly
      established guidelines to more precisely define the role of RCPs in performing
      procedures in the ICU. Published studies demonstrate the added value of RCPs'
      collaboration in several ICU activities, including placement of arterial
      catheters, sampling of arterial blood gases, endotracheal intubation, and
      management of and weaning from mechanical ventilation. Other ICU activities in
      which RCPs participate include assisting with bronchoscopy, obtaining
      haemodynamic measurement, and indirect calorimetry and supporting specialised
      techniques such as extracorporeal membrane oxygenation (ECMO) and continuous veno
      venous haemofiltration and/or haemodiafiltration (CVVH/CVVHD). Based on the
      demonstrated impact of RCPs and their technical and cognitive training, a
      continuing role expansion for RCPs in the ICU is expected.

PMID- 9777092
TI  - Continuous renal replacement therapy: continuous blood purification in the
      intensive care unit.
AB  - Severe acute renal failure (SARF) occurs when renal dysfunction is such that
      haemodialysis or haemofiltration becomes necessary to maintain homeostasis. SARF
      is increasingly seen in association with multiorgan failure and has become a
      predominantly Intensive Care Unit disorder. Because of this change in
      epidemiology, the treatment of SARF has evolved from being exclusively
      nephrologist and intermittent haemodialysis-based to being mostly intensivist and
      continuous haemofiltration-based, particularly in European countries with a
      strong ICU tradition and in Australia. Continuous renal replacement therapy
      (CRRT) has several advantages in critically ill patients, including greater
      flexibility, excellent haemodynamic tolerance, outstanding fluid balance control,
      excellent control of uraemia, prevention of cerebral oedema, ability to provide
      full and aggressive nutrition, and a possible anti-inflammatory effect. The blood
      purification effect of CRRT may, in fact, go beyond the simple control of
      uraemia. Several animal studies have now shown that CRRT attenuates the
      haemodynamic consequences of bacteraemia or endotoxaemia. Such studies have also
      shown that increasing the intensity of fluid exchange may offer further
      beneficial effects in the setting of sepsis. In the light of these findings, CRRT
      is moving into the area of adjuvant treatment of sepsis, and pilot randomized
      controlled trials are being conducted to test the hypothesis that CRRT, either in
      standard or high fluid exchange volumes, attenuates the inflammatory effects of
      sepsis in humans. In the future, the use of CRRT may extend beyond its initial
      scope into the area of adjuvant management of sepsis and continuous blood
      purification may become part of a complex multifaceted approach to multiorgan
      dysfunction.

PMID- 9777094
TI  - Combined high-frequency ventilation (CHFV) in the treatment of acute lung injury-
      a case report.
AB  - A 22-year-old man was admitted to a district general hospital with chest
      injuries, a ruptured spleen and limb fractures, sustained in a road traffic
      accident. After an emergency splenectomy, the patient developed unilateral
      pulmonary oedema with hypoxaemia which was resistant to both conventional
      controlled mechanical ventilation (CMV) and independent lung ventilation (ILV).
      He was transferred to a specialist cardiothoracic unit where high frequency jet
      ventilation (HFJV) also failed to achieve adequate oxygenation. Combined high
      frequency ventilation (CHFV), using high frequency pulses from a Bromsgrove
      Penlon Jet ventilator superimposed onto small tidal volumes from an Engstrom
      Erica improved oxygenation rapidly to allow decreases in inspired oxygen fraction
      (FiO2), peak airway pressure (PAWP) and positive end expiratory pressure (PEEP).
      Progressive weaning from ventilatory support was then possible over five days.
      CHFV is a valuable technique in the treatment of acute catastrophic lung injury
      and needs wider recognition.

PMID- 9777093
TI  - Foregoing life support in medically futile patients.
AB  - Advances in medical technology have rendered the ability to provide prolonged
      physiologic support of incurable or terminally ill patients commonplace in the
      intensive care unit. In tandem, there has been a global shift in the
      intensivist's mindset from solely pursuing an unrelenting course of aggressive
      therapy, to a recognition of the limitations of intensive care and the
      appropriate discontinuance of nonbeneficial therapy. Underpinning this shift
      remains the physician's adherence to the ethical principles of beneficence,
      nonmaleficence, and disclosure; the patient's right to autonomy and self
      determination; and the community's right to just distribution of medical
      resources. When the doctor assumes the role of patient advocate, and assesses
      illness severity and evaluate recovery, or lack of, to a quality consistent with
      the patient's own life philosophy, he is able to communicate to the family a
      course of action that is in the patient's best interest. A consensus on
      withholding or withdrawal of care is often then achieved. The process of
      foregoing or withdrawing life-sustaining therapy itself, must be carried out with
      sensitivity and empathy, with the primary goal of providing comfort and reducing
      suffering.

PMID- 9777095
TI  - A case of pseudohyperkalaemia and thrombocytosis.
AB  - An unusual cause of "hyperkalaemia" was observed in a neurosurgical patient
      admitted to our intensive care unit. The cause of the hyperkalaemia was not known
      initially and treatment with cation ion exchange resin was initiated to lower the
      elevated serum potassium level. The concurrent occurrence of thrombocytosis and
      hyperkalaemia raised the possibility of psuedohyperkalaemia associated with
      thrombocytosis. Simultaneous measurement of plasma and serum potassium with the
      Hitachi 917 Analyzer (indirect ion selective electrode, coefficient of variation
      = 1% to 2%) confirmed the diagnosis. Correlation between thrombocytosis and
      pseudohyperkalaemia was found to be highly significant (r = 0.54; P = 0.014). It
      is estimated that for for every 100 x 10(9)/L of platelets, an increase of 0.07
      to 0.15 mmol/L of potassium is expected. In thrombocytosis, plasma rather than
      serum potassium should be measured.

PMID- 9777097
TI  - Planning and design of a surgical intensive care unit in a new regional hospital.
AB  - Critical care unit design has profound effect on work efficiency, infection
      control and psychology of patients and staff working in the area. A
      multidisciplinary team was involved in the design and planning of a surgical
      intensive care unit (SICU) in a new regional hospital. A workgroup consisting of
      clinicians, nurses, engineers and hospital administrators were involved in its
      planning. The Hospital Planning Committee oversaw the activities of the workgroup
      to ensure co-ordination and integration of the unit plan with the hospital plan.
      The issue on "single room" versus "open unit" patient room design was much
      debated. "Single room" concept was adopted and the cubicles were arranged
      radially facing a central station. Access of patients from the operating theatres
      and wards to the SICU was an important consideration. The design and facilities
      of various rooms in the SICU are described. New technology such as the automated
      guided vehicle, pneumatic tube system, floor mounted power column and closed
      circuit television were some of the useful assets available in the unit.

PMID- 9777096
TI  - Management training in critical care medicine.
AB  - Critical care medicine is the only specialty fellowship which requires formal
      training in administrative and management skills by its certifying organisation.
      The rationale for this is the fact that critical care is responsible for some 1%
      of gross national product, 10% of hospital beds and 30% of acute hospital costs
      in the USA. The curriculum required during the fellowship training has been
      defined. In order for critical care medicine to continue to grow as an academic
      as well as a successful institutional clinical service, it is important that
      quality training be provided in this non-clinical part of the fellowship
      curriculum as well as the clinical aspects.

PMID- 9777098
TI  - [Antifungal chemotherapy. Progress and problems].

PMID- 9777099
TI  - [Biosynthesis of leucine aminopeptidase by Xanthomonas rubrilineans 67 in culture
      with various concentrations of nitrogen containing compounds].
AB  - The dynamics of consumption of amine and ammonium nitrogen and glucose in the
      process of Xanthomonas rubrilineans 67 growth and biosynthesis of leucine
      aminopeptidase was studied. It was shown that the rate of leucine, alanine and
      glycine consumption as a source of amine nitrogen out of 16 amino acids was the
      highest during the fermentation. Addition of these three amino acids or their
      mixtures to the medium at definite stages of the fermentation process increased
      the leucine aminopeptidase biosynthesis by 50 to 100 per cent. Ammonium nitrogen
      was not used by X.rubrilineans 67. The consumption of glucose during the
      fermentation was even: by the 24th hour of the process the medium contained about
      10 per cent of the glucose initial concentration. The optimal temperature for the
      culture growth and leucine aminopeptidase biosynthesis was determined. It was
      shown to be 28 degrees C. Higher aeration increased the culture productivity.

PMID- 9777100
TI  - [Antimicrobial and membranolytic activity of sterically hindered phenols].
AB  - Antimicrobial activity of some complicated space phenols (screened) was studied.
      The compounds had different activities against grampositive bacteria and were
      inactive against gramnegative microbes. Di-tertiary butyl derivatives of
      pyrocatechol and resorcin showed the highest activities. The MICs of such
      derivatives for the collection strains of Bacillus megaterium, Bacillus subtilis
      and Staphylococcus aureus were 8 to 30 micrograms/ml and exceeded 6-25 times
      those of the nonsubstituted analogs. The derivatives of pyrocatechol and resorcin
      impaired the membrane permeability in susceptible intact cells of B.megaterium
      and S.aureus 209P and had no effect on the membrane permeability of the
      Escherichia coli resistant cells. In concentrations up to 200 micrograms/ml the
      nonsubstituted analogs of pyrocatechol and resorcin did not impair the membrane
      permeability in the intact cells of the above bacteria. Di-tertiary butyl
      derivatives of pyrocatechol and resorcin had lytic activity with respect to
      cytoplasmic membranes (protoplasts) of B.megaterium and had no lytic action on
      E.coli spheroplasts. The antimicrobial spectrum correlated with the
      membranotropic properties of the compounds. It was suggested that the target of
      the antimicrobial action of the screened phenols was the bacterial cell
      cytoplasmic membrane.

PMID- 9777101
TI  - [Characteristics of fauces microflora in children treated in intensive care
      units].
AB  - Characteristic features of fauces aerobic microflora in children treated in
      intensive care units (ICU) were analysed. For comparison fauces microflora in
      children outpatients and in children patients from general surgical units was
      investigated. A retrospective analysis of all the smears without exception for 2
      years (a total of 2120) revealed a direct dependence of the changes in the fauces
      microflora composition on the patient condition and the antibiotic load. It was
      shown that the fauces indigenic microflora in ICU patients was more often
      replaced by enterococci, gramnegative enteric bacteria and nonfermenting bacteria
      which are not usual under the normal conditions. The flora in such cases was
      represented by monoculture. Thus, microorganisms natural for the fauces i.e.
      Haemophilus influenzae and Neisseria spp. were not practically detected in the
      fauces of the ICU patients (0.5 and 0.4 per cent, respectively). Grampositive
      cocci in the children of the surgical units and in the outpatients included alpha
      hemolytic streptococci in association with beta-hemolytic or nonhemolytic
      streptococci. No such bacteria were isolated from the ICU newborns. The
      associations of gramnegative organisms from the ICU patients included 40
      variants. Seventy-eight association variants of Pseudomonas aeruginosa were
      mainly represented by the combinations with Serratia spp. and Klebsiella spp. as
      well as with coagulase negative staphylococci or enterococci, especially in the
      ICU newborns. The results of the study demonstrated that the target-aimed
      antibiotic therapy providing eradication of P.aeruginosa in the ICU patients was
      not always justified because of possible superinfection practically due to any
      organism from the association. Massive antibiotic therapy with pressing on
      gramnegative flora in the ICU patients induced selective contamination of the
      mucosa by polyresistant enterococci thus increasing their potential role in the
      development of hospital infections.

PMID- 9777103
TI  - [New fluoroquinolones: characteristics of antimicrobial effect and
      pharmacokinetics].

PMID- 9777102
TI  - [Epidemiology of infectious inflammatory diseases and role of Candida in
      newborns].
AB  - The results of a 20-year microbiological monitoring of full-term newborns with
      infectious inflammatory diseases hospitalized from maternity homes of Moscow are
      presented. The incidence of candidiasis within that period was shown to increase
      7 times at the account of the events of cutaneous and mucocutaneous candidiasis,
      gastrointestinal candidiasis and candidiasis of the central nervous system. One
      of the sources of the endogenic contamination of the newborns and infants was
      their intestinal microflora. In 4.6 per cent of the patients the meconium
      contamination by Candida was stated during the first days after the birth.

PMID- 9777104
TI  - [Drugs of microbial origin for treatment of atherosclerosis].

PMID- 9777106
TI  - Preaching by the unconverted.

PMID- 9777107
TI  - Obstructive sleep apnoea.

PMID- 9777108
TI  - The causes of sporadic and 'senile' chorea.
AB  - BACKGROUND: Although 'senile' chorea is commonly listed in the differential
      diagnosis of chorea, the condition is poorly defined. Indeed, the existence of
      such an entity is debated. There are few contemporary prospective studies of
      sporadic chorea in the elderly. METHODS: Detailed prospective study of patients
      presenting with undiagnosed chorea over a three year period to a Movement
      Disorder Clinic. RESULTS: Twelve patients, aged 50 to 89 years, were identified.
      The final diagnoses were Huntington's disease, confirmed on genetic testing in
      six, antiphospholipid antibody syndrome in two, and hypocalcaemia, tardive
      dyskinaesia and basal ganglia calcification in each of the three remaining cases.
      Only one patient remained undiagnosed despite extensive investigation.
      CONCLUSIONS: The majority of patients with 'senile' chorea actually have
      Huntington's disease even in the absence of a family history. Rarer causes of
      chorea still need to be considered in the elderly when Huntington's disease has
      been excluded by DNA analysis.

PMID- 9777109
TI  - Evaluation of a computer based package on electrocardiography.
AB  - BACKGROUND: Opportunities for interactive learning in electrocardiography are
      limited--particularly at postgraduate level. In medical education, increasing use
      is being made of the electronic medium and various materials have been developed
      to improve clinicians' skills. AIMS: To test and evaluate the learning of
      electrocardiography among health professionals. METHODS: A software package,
      containing a tutorial on electrocardiography and a self-assessment programme of
      140 electrocardiograms (ECGs) was constructed. Seventy-two health professionals
      were recruited into the study and tested before and after the study period.
      Participants were randomly allocated to one of three groups: control (no study
      material), tutorial or computer. The tutorial group participated in a series of
      tutorials and the computer group were provided with a CD-ROM containing study
      material for them to use in their own time. The results were assessed for
      statistical significance between all groups using analysis of variance
      techniques. RESULTS: Sixty-one individuals completed the study. Each of the three
      groups was pre and post tested on their knowledge of electrocardiography and
      their ability to interpret ECGs. The computer group was the only group to achieve
      a significant increase in performance in their knowledge on electrocardiography
      and in their ability to interpret ECGs. CONCLUSIONS: Suitably structured computer
      programmes are effective in helping clinicians understand electrocardiography and
      interpret ECGs.

PMID- 9777110
TI  - NSAIDs and faecal blood loss in elderly patients with osteoarthritis: is plasma
      half-life relevant?
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) vary in their degree of
      gastrointestinal (GI) toxicity. NSAIDs with longer half-lives are of particular
      concern as they may be more toxic in the elderly. AIM: To compare the GI
      toxicity, by measurement of faecal blood loss, of short, intermediate and long
      half-life NSAID treatments compared with control in elderly patients with
      osteoarthritis. METHODS: Twenty-three patients, mean age 69 years, with
      osteoarthritis requiring NSAID treatment, received treatment with diclofenac 100
      mg/day, naproxen 750 mg/day and piroxicam 20 mg/day, representing a short, medium
      and long half-life NSAID respectively, in a double-blind, randomised, three way,
      cross-over block design. In each case, a three week washout control phase was
      followed by active treatment phases of two weeks each with three week washout
      between treatment phases. RESULTS: Faecal blood loss, collected over 72 hours at
      the end of each treatment phase, was measured by 51Cr-labelled erythrocyte
      method. Comparison was made of mean 24 hour faecal blood loss with each treatment
      compared with control using repeated measures analysis of variance. Eighteen
      patients completed all phases of the study. Three patients were withdrawn due to
      GI bleeding; two during diclofenac treatment and one during treatment with
      piroxicam. Mean 24 hour faecal blood loss with diclofenac (0.53 mL +/- 0.21) was
      not significantly different from control (0.28 mL +/- 0.06), whereas it was
      significantly increased with naproxen (2.76 mL +/- 2.22) and piroxicam (1.16 mL
      +/- 0.62), p = 0.0013. CONCLUSION: A short half-life NSAID was associated with
      lower GI toxicity than a medium and long half-life NSAID, as measured by faecal
      blood loss.

PMID- 9777111
TI  - Continuous and intermittent infusion of coagulation factor concentrates in
      patients undergoing surgery: a single centre Australian experience.
AB  - BACKGROUND: Haemophilia patients require large doses of coagulation factor
      concentrates to optimise haemostasis at the time of surgery. The superior
      pharmacokinetic profile of continuous infusion over intermittent bolus
      administration may be more advantageous. AIMS: We report our experience using
      coagulation factor concentrates delivered by continuous infusion in patients
      undergoing surgery. METHODS: A retrospective case notes review of all patients
      treated by continuous infusion at Royal Prince Alfred Hospital (RPAH) over a two
      year period and a comparison of two cohorts of patients undergoing orthopaedic
      surgery using either continuous infusion or bolus factor VIII (FVIII) replacement
      therapy. Patients received a pre-operative bolus of factor concentrate (AHF,
      Immunine or Recombinate) followed by a continuous infusion calculated according
      to weight, clearance and target plasma concentration. RESULTS: Twenty-one (19 M,
      two F) with haemophilia or von Willebrand's disease underwent 26 surgical
      procedures between July 1995 and July 1997. The mean total consumption of
      concentrate per patient was 36,676 units (range 6750-82,000) infused over a mean
      period of 7.6 days (range one-16). One patient experienced minor surgical
      bleeding on treatment and one patient developed severe bleeding into the replaced
      joint off infusion requiring additional boluses of treatment. In a separate
      analysis, ten of these patients who underwent major orthopaedic surgery were
      compared to a historic cohort (n = 8) of patients who received bolus injections
      for similar types of operations. CONCLUSIONS: Coagulation factor concentrates
      delivered by continuous infusion have major clinical and economic advantages in
      the surgical management of patients with haemophilia.

PMID- 9777112
TI  - Smoking habits and cessation programme in an Australian teaching hospital.
AB  - BACKGROUND: Data on prevalence of cigarette smoking by hospital employees are
      limited in Australia, but anecdotal evidence suggests that many health sector
      employees continue to smoke despite abundant evidence regarding the harmful
      effects of this habit. Nicotine is an addictive drug and arguably this should be
      known better in the health industry than in any other industry. Despite having
      this knowledge at their disposal, health sector employers rarely provide
      assistance to employees, relying instead on restrictive policies to reduce
      smoking in the workplace. METHODS: To assist employees to quit smoking, we
      instituted a medium intensity Stop Smoking Programme, run by a clinical
      pharmacist offering nicotine patches and support on a weekly basis. A principal
      aim of the service was to redress the imbalance between the availability of
      cigarettes and the most effective nicotine replacement therapy, the trandermal
      nicotine patch. Following 18 months operation of this service, we surveyed
      hospital employees to ascertain smoking rates and views on smoking cessation in
      this South Australian teaching hospital. RESULTS: In the first 18 months of
      operation, 111 staff members availed themselves of the service. At the first
      follow up period (three months), 21 were not contactable, 29 were successful in
      not smoking and 61 were still smoking. Six of the 29 who were not smoking at
      three months resumed smoking by six months, and a further four resumed smoking by
      12 months. At the time of this report, 12 of the remaining 19 non smokers had
      completed two years since quitting and a further three of these had resumed
      regular smoking by this time. The cost of providing the service was modest at
      approximately $180.00 per known successful quitter. Results from the survey
      showed that 12.4% of hospital employees were regular smokers. Smoking prevalence
      was not equally distributed with female employees being twice as likely to smoke
      as their male counterparts and employees in the catering department having the
      highest smoking prevalence (23.8%). CONCLUSIONS: Although the prevalence of
      cigarette smoking by employees of this teaching hospital is lower than for the
      general community, health sector employers can reduce smoking prevalence further
      by providing assistance to their employees to quit smoking. The Stop Smoking
      Programme we describe is effective and could be replicated by other hospitals and
      similar organisations.

PMID- 9777114
TI  - High prevalence of retinopathy among type 2 diabetic patients with no visual
      complaint.

PMID- 9777113
TI  - Mycobacterial lymphadenitis in eastern Sydney.
AB  - BACKGROUND: There has been a resurgence of tuberculosis (TB) in the developed
      world, especially extrapulmonary manifestations, of which lymphadenitis is the
      most common. We reviewed all cases of mycobacterial lymphadenitis notified in the
      eastern suburbs of Sydney from 1989 to 1996. AIMS: To review all cases of
      mycobacterial adenitis in eastern Sydney. METHODS: This was a retrospective
      review of the medical records of 54 patients (aged 1.2 to 84 years), recruited
      from all notifications of TB presenting as lymphadenitis at Prince of Wales,
      Sydney Children's and St Vincent's Hospitals. RESULTS: There were two distinct
      groups: Group 1, patients with Mycobacterium tuberculosis (MTB), n = 37 (68.5%),
      Group 2, patients with atypical mycobacteria, n = 17 (31.5%). For Group 1, 83.3%
      were foreign born and 18.9% were positive for the human immunodeficiency virus
      (HIV). Disease involved single node groups in 73% (the cervical chain was
      involved in 70.1%). Complete resolution of lymphadenopathy at conclusion of
      treatment occurred in 73.1%. Outcome was not documented in 13.5%, of the rest;
      83.8% completed treatment; 2.7% were lost to follow up before treatment
      concluded; 2.7% were still being seen at the time of writing and 10.8% died
      within six months of treatment starting (all were HIV positive). HIV positive
      patients had more diffuse disease. Group 2 were all Australian born. They
      comprised children less than six years who were all HIV negative and adults (aged
      30-55 years) who were all HIV positive. The children were all treated surgically
      with 80% having complete resolution of their modes. Those adults with HIV had a
      mortality of 83.3% during treatment. CONCLUSIONS: In eastern Sydney lymphadenitis
      caused by MTB in the HIV negative population is mostly seen in those who are
      immigrants. Our large proportion of HIV positive patients tended to have diffuse
      disease and a high mortality. The reporting of outcomes was poor and in a greater
      than expected number of outcome and follow up were inadequately documented.

PMID- 9777115
TI  - Central nervous system relapse in acute promyelocytic leukaemia treated with all
      trans retinoic acid.

PMID- 9777116
TI  - Emergency coronary artery bypass grafting (CABG) after failed coronary artery
      intervention--caution regarding the combined use of aspirin, ticlopidine and
      abciximab.

PMID- 9777117
TI  - Mediastinal nodal tuberculosis presenting as immune thrombocytopenia.

PMID- 9777119
TI  - Successful surgical treatment of thromboembolic pulmonary hypertension.

PMID- 9777118
TI  - Early rapid onset lipohypertrophy in a patient with type 1 diabetes mellitus.

PMID- 9777120
TI  - Primary aortoenteric fistula.

PMID- 9777121
TI  - A role for surgery in the management of multi-drug-resistant tuberculosis (MDRTB)

PMID- 9777122
TI  - Spread of influenza A virus infection in hospitalised patients with cancer.

PMID- 9777123
TI  - Is hypokalaemic periodic paralysis more prevalent in Maori?

PMID- 9777124
TI  - Calcitriol mediated hypercalcaemia in a T cell rich B cell lymphoma.

PMID- 9777125
TI  - Rehabilitation length of stay after hip fracture.

PMID- 9777126
TI  - Guillain-Barre syndrome and optic neuritis after Mycoplasma pneumoniae infection.

PMID- 9777127
TI  - Systemic lupus erythematosus (SLE) and neonatal morbidity and mortality.

PMID- 9777128
TI  - A burden to bear in systemic lupus erythematosus (SLE)

PMID- 9777129
TI  - Dysphagia, hoarseness and a collapse.

PMID- 9777130
TI  - Can we improve on front-loaded alteplase (r-TPA)?
AB  - The method of administration of alteplase has evolved since its introduction to
      clinical practice in the late 1980s. The initial dosage regimen of a graded
      administration of 100 mg was replaced by the front-loaded weight adjusted
      regimen, the efficacy of which was demonstrated in the GUSTO 1 trial. Double
      bolus administration was shown to achieve superior TIMI 3 patency of the infarct
      related artery in a small angiographic study, but the COBALT trial failed to show
      equivalence and indeed showed a slightly higher mortality and incidence of
      stroke, so cannot be recommended. Reteplase, a deletion mutant of alteplase, also
      showed superior efficacy in achieving coronary patency but no clinical
      superiority in outcomes in the 15,000 patient GUSTO 3 trial. The case of
      administration of reteplase, however, has some attraction as an alternative to
      alteplase. Trials of newer agents based on further modifications of alteplase are
      ongoing, but at present the front-loaded alteplase regimen remains the standard
      for clinical practice.

PMID- 9777131
TI  - Alteplase (r-TPA) vs streptokinase.
AB  - The GUSTO trial and an Australian consensus meeting in 1993 led to the
      recommendation that recombinant tissue plasminogen activator (r-TPA) was the
      preferred thrombolytic in patients with acute myocardial infarction (AMI) and ST
      segment elevation under the age of 75, whose infarction was anterior, who could
      be treated within four hours of the onset of symptoms and who did not have a
      contraindication to thrombolysis. Available data suggest that streptokinase (SK)
      should not be administered in a patient who has received this drug three days or
      more previously. New data on the risks of stroke confirm that the use of r-TPA is
      associated with a higher risk of intracranial haemorrhage than SK, and those with
      a high risk profile for intracranial haemorrhage (hypertension and advanced age)
      should receive SK rather than r-TPA. It may be justified to give r-TPA to any
      patient with a large infarct regardless of location, within four hours of the
      onset of infarction in an attempt to achieve TIMI flow grade 3 (complete)
      reperfusion, reduce mortality and improve left ventricular function and clinical
      outcomes. The focus for the future will be on how to treat more patients earlier
      with thrombolytic agents, rather than the choice of agent.

PMID- 9777132
TI  - Thrombolytic eligibility.
AB  - The Fibrinolytic Therapy Trialists' Collaborative Group has demonstrated that
      patients without clear contraindications who present with ischaemic chest pain
      within 12 hours of the onset of symptoms and who have ST segment elevation or
      bundle branch block on their electrocardiogram (ECG), will benefit from
      thrombolytic therapy. Therefore the treatment of patients presenting with
      ischaemic chest pain is guided by the initial ECG. This paper addresses the
      question of thrombolytic eligibility in several subsets of patients who may
      benefit from treatment. It also explores the data which confirm the benefit for
      patients presenting with an inferior myocardial infarction and for those
      presenting from six-12 hours after the onset of symptoms. In conclusion,
      thrombolytic therapy should not be routinely withheld from diabetic or elderly
      patients, menstruating women and patients who have had cardiopulmonary
      resuscitation.

PMID- 9777133
TI  - Refining the risk-benefit equation for thrombolysis: how to identify the low risk
      patient before administering thrombolytic therapy.
AB  - In view of the relative risk of intracranial haemorrhage and major bleeding with
      thrombolytic therapy, it is important to identify as early as possible the low
      risk patient who may not have a net clinical benefit from thrombolysis in the
      setting of acute myocardial infarction. An analysis of 5434 hospital-treated
      patients with myocardial infarction in the Perth MONICA study showed that age
      below 60 and absence of previous infarction or diabetes, shock, pulmonary oedema,
      cardiac arrest and Q-wave or left bundle branch block on the initial ECG
      identified a large group of patients with a 28 day mortality of only 1%, and one
      year mortality of only 2%. Identification of baseline risk in this way helps
      refine the risk-benefit equation for thrombolytic therapy, and may help avoid
      unnecessary use of thrombolysis in those unlikely to benefit.

PMID- 9777134
TI  - The primary angioplasty vs thrombolysis debate.
AB  - Early and complete coronary reperfusion can improve survival in myocardial
      infarction. Primary angioplasty can achieve TIMI grade 3 flow (complete
      restoration) in over 90% of cases. In comparison thrombolysis can achieve TIMI
      grade 3 flow in only just over 50%. Comparative trials have shown superior rates
      of death and reinfarction with a low haemorrhagic risk with PTCA compared with
      thrombolysis. Early clinical trials showed a clear superiority of primary
      angioplasty over thrombolysis but larger trials with larger number of endpoints
      have shown less impressive superiority. Wider application in community studies
      has not shown the benefits promised in the earlier studies, possibly due to
      dilution of experience. The impact of newer stent regimens vs nonnewer
      thrombolytic and antithrombotic regimens can only be determined by further
      clinical trials.

PMID- 9777135
TI  - Intervention with PTCA and CABG following thrombolysis for acute myocardial
      infarction. Australian data from GUSTO 1 (1991-3) and International Study Group r
      TPA-Streptokinase Mortality (1989) trials. Global Utilisation of Streptokinase
      and Tissue.
AB  - The patterns of revascularisation with percutaneous transluminal coronary
      angioplasty (PTCA) and coronary artery bypass graft (CABG) surgery in the GUSTO 1
      trial patients in Australia are described. In comparison with rates documented in
      earlier trials of thrombolytic therapy in Australia, the rates of
      revascularisation post-thrombolysis increased by 50%, primarily due to a doubling
      in the rate of use of PTCA. However, the rates were low by international
      comparisons. There were marked variations in the rates of revascularisation
      between States, but no correlation with differences in mortality between States.
      The main predictors of post thrombolysis PTCA were prior angina, mild infarction
      and access to PTCA facilities.

PMID- 9777136
TI  - Heparin management in acute myocardial infarction (AMI).
AB  - Antithrombotic agents have been shown to be beneficial in the setting of acute
      coronary syndromes, and as an adjunct to thrombolysis for acute myocardial
      infarction (AMI). The optimal type and dosing of antithrombotic drug, however,
      remains elusive. Heparin, the agent most commonly used, has several limitations,
      the most important of which may be its inability to inhibit clot-bound thrombin.
      Newer, direct thrombin inhibitors (such as hirudin) provide potent and
      predictable thrombin inhibition and are able to inhibit clot-bound thrombin. Both
      heparin and hirudin can carry a substantial risk of haemorrhage, however, and
      thrombin activity is likely to rebound after discontinuation of either agent.
      Further, the relationships of antithrombotic/thrombolytic dosing, measures of
      anticoagulation (such as APTT), and clinical outcomes are not always clear.
      Nonetheless, from the data available from large, randomised trials, intravenous
      heparin should remain a standard adjunct to thrombolytic therapy for AMI.

PMID- 9777137
TI  - The GUSTO 2b and related studies. Global Use of Strategies to Open Occluded
      Coronary Arteries.
AB  - Direct anti-thrombin inhibitors such as hirudin have theoretical advantages over
      heparin. Two large studies in acute coronary syndromes were designed to test the
      thrombin hypothesis by demonstrating improved outcomes in hirudin treated
      patients. TIMI 9 assessed the effect of hirudin in patients with ST elevation
      receiving thrombolytic therapy. GUSTO 2 assessed the full spectrum of acute
      coronary syndromes of ST elevation and non-ST elevation. Over 15,000 patients
      were entered into the studies and no major benefit was demonstrated for hirudin.
      This may, however, relate to endpoints measured and the timing of the anti
      thrombin.

PMID- 9777138
TI  - Hirudin (desirudin) and Hirulog (bivalirudin) in acute ischaemic syndromes and
      the rationale for the Hirulog/Early Reperfusion Occlusion (HERO-2) Study.
AB  - Unlike unfractionated heparin, direct thrombin inhibitors such as hirudin and
      Hirulog inhibit clot-bound as well as fluid-phase thrombin, escape neutralisation
      by platelet secretion products, do not require monitoring, and are unassociated
      with immune thrombocytopenia. They have been shown to have modest advantages over
      heparin when given after thrombolytic therapy, reducing reinfarction by 14%. In
      the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO 2b) trial,
      patients treated with streptokinase and adjunctive hirudin had a reduction in
      death or myocardial infarction of 40% at 30 days (8.6% with hirudin versus 14.4%
      with heparin, p = 0.004). In the Hirulog Early Reperfusion/Occlusion (HERO 1)
      trial, 48% of patients who received Hirulog as adjunctive therapy with
      streptokinase had Thrombolysis in Myocardial Infarction (TIMI) trial grade 3 flow
      in the infarct-related artery, compared with 35% of patients who received heparin
      with streptokinase (p < 0.05). The HERO 2 study, involving 17,000 patients, will
      test the hypothesis that Hirulog and aspirin given before streptokinase will
      reduce mortality compared with aspirin plus heparin. Early administration of
      direct thrombin inhibitors may potentially improve the outcome of patients
      treated with thrombolytic therapy.

PMID- 9777139
TI  - Low molecular weight heparins in acute ischaemic syndromes.
AB  - Thrombus formation and ongoing generation play a major role in the pathogenesis
      of unstable angina and myocardial infarction (MI). Unfractionated heparin is
      widely used as an adjunctive therapy in the management of acute ischaemic
      syndromes, but it has a number of limitations including inter-patient
      variability, need for monitoring, and the fact that its use may be associated
      with thrombocytopenia. Low molecular weight heparins have pharmacological and
      pharmacokinetic properties that may result in better clinical outcomes and
      safety. They are easy to administer and do not require monitoring. Low molecular
      weight heparins have been shown to reduce mortality and the incidence of MI and
      recurrent ischaemia compared with placebo in patients with unstable angina and
      non-Q-wave MI, and have a more predictable anticoagulant effect than standard
      unfractionated heparin. They also can be used long term in the outpatient
      setting, in the form of self-administered subcutaneous injections. The clinical
      relevance of these new developments is still being defined in ongoing clinical
      trials and cost-effectiveness analyses.

PMID- 9777140
TI  - New antiplatelet agents.
AB  - Aspirin is an established therapy for the management of acute myocardial
      infarction (AMI) and unstable angina. Secondary prevention with chronic aspirin
      therapy is also indicated for patients with stable angina. Aspirin inhibits cyclo
      oxygenase-I, a key enzyme in the biosynthetic pathway leading to the production
      of thromboxane A2. It therefore inhibits only one of the many activation pathways
      leading to platelet aggregation. Other antiplatelet agents that have also been
      evaluated in clinical trials include ticlopidine and clopidogrel, which inhibit
      adenosine diphosphate-mediated platelet aggregation, but these agents are known
      to be effective against only one of the 90 known agonists that stimulate platelet
      aggregation. The final common pathway for platelet aggregation involves the
      glycoprotein IIb/IIIa receptor combining with fibrinogen. Several inhibitors of
      the glycoprotein IIb/IIIa receptor have been developed and have an important role
      as adjunctive therapy in angioplasty. Recent trials have been performed in
      patients with unstable angina, and trials of adjunctive therapy are currently
      underway in patients receiving thrombolysis for AMI, and for secondary
      prevention. These drugs have various different features, including specificity
      for blockade of the glycoprotein IIb/IIIa receptor, half life, duration of the
      haemostatic effect and potential for antigenicity. Recently concluded and ongoing
      trials of both intravenous and oral agents are expected to provide further
      support for the introduction of these agents into clinical management of patients
      with acute coronary syndromes.

PMID- 9777141
TI  - Detection of reperfusion after thrombolytic therapy by the analysis of released
      biochemical markers.
AB  - Although the advent of thrombolytic therapy for acute coronary occlusion has
      substantially reduced the mortality of acute myocardial infarction (AMI), the
      best available thrombolytic regimens only achieve adequate reperfusion in a
      little over half the patients who are treated. The ability to detect failure of
      reperfusion by non-invasive means would permit further therapy in this patient
      group who currently have a high mortality. As coronary reperfusion causes a rapid
      release of many myocardial proteins into the blood stream, analysis of the rate
      of release of markers such as myoglobin, troponin, and creatine kinase (CK)
      during the first 90 minutes after thrombolytic therapy can identify about 80% of
      the patients in whom thrombolytic therapy has been ineffective. An ideal marker
      of reperfusion would be rapidly released after reperfusion, rapidly cleared from
      the circulation, highly myocardial specific, and amenable to rapid quantitative
      assay to permit 'real time' determination of coronary patency status. At present
      myoglobin and cardiac troponins appear most promising for detection of
      reperfusion, but other markers such as CK isoforms may prove useful if reliable
      rapid assays become available.

PMID- 9777142
TI  - The corrected TIMI frame count. The new gold standard?
AB  - Over the last decade Thrombolysis in Myocardial Infarction (TIMI) flow grades
      have been the gold standard for the assessment of efficacy of infarct-artery
      reperfusion. However, with the introduction of core angiographic laboratories,
      the reproducibility of TIMI flow grades has been questioned. The corrected TIMI
      frame count (CTFC) has been developed as a more reproducible method of
      quantifying infarct artery blood flow after myocardial infarction (MI). We have
      utilised the CTFC in two studies to examine infarct-artery blood flow. In the
      Hirulog in Early Reperfusion and Occlusion (HERO 1) study, the CTFC was measured
      at 90-120 minutes after administration of aspirin, streptokinase and either
      Hirulog or heparin. Only 27% of patients had a normal CTFC (< or = 27) in the
      infarct-related artery. Patients with a prolonged CTFC (> 27) had more abnormal
      left ventricular function (LVF) as measured by the mean chord score in the 'area
      at risk' (-2.51 vs -2.06, p = 0.02), on left ventriculography. In a second study,
      infarct-artery flow was examined four weeks and one year after MI. At four weeks,
      only 43% of patients with patient infarct-related arteries had a 'normal' CTFC of
      < or = 27. A prolonged CTFC at four weeks was a univariate predictor of increased
      reocclusion at one year (p = 0.001). CTFCs are frequently abnormal in patent
      infarct-related arteries, and predict reocclusion. Whether frame counting is a
      better predictor of late clinical outcomes than the TIMI flow grade needs to be
      prospectively examined in large clinical trials.

PMID- 9777143
TI  - Issues in extrapolating from clinical trials to clinical practice and outcomes.
AB  - Extrapolation of clinical trial results to clinical practice requires
      consideration of whether the trial patients were representative of clinical
      practice, whether the trial therapy studied was optimal, whether the sample size
      was adequate, and the impact of adjunctive treatments. In thrombolytic trials in
      particular, regional variations in attitudes to coronary angiography may have
      affected outcomes. Clinical trial results need to be interpreted in the light of
      the cost effectiveness of the application. The assessment of clinical outcomes
      depends on interplay between the structure and process of care, patient factors
      and chance. Large standardised databases are necessary to assess clinical
      practice and outcomes.

PMID- 9777144
TI  - Molecular typing of avian Escherichia coli isolates by random amplification of
      polymorphic DNA.
AB  - Escherichia coli is a common inhabitant of the gastrointestinal tract of most
      animals. Like most pathogenic E. coli, avian isolates cannot be distinguished
      biochemically from the normal commensals inhabiting the gastrointestinal tract of
      birds. Using a molecular approach, we were able to identify genetic differences
      among avian E. coli isolates by restriction fragment length polymorphism (RFLP)
      and random amplification of polymorphic DNA (RAPD) by the polymerase chain
      reaction (PCR). Several different RFLPs were observed among avian E. coli
      isolates using DNA probes for 16S ribosomal RNA genes (rrn) and insertion
      sequence elements (IS2). We were also able to observe differences in DNA banding
      patterns generated by RAPD analysis. Similarities and differences among avian E.
      coli were discernible using RFLPs and RAPD analysis, whereas conventional
      bacteriological methods failed to differentiate these isolates. Based on RAPD
      patterns, avian E. coli appear to be genetically diverse. Of 16 different RAPD
      types (RT) encountered, 84% of E. coli fell into seven major RTs. One RT was
      present in clinical isolates but absent from the commensals isolated in this
      study. Many of these different E. coli RTs were not geographically restricted to
      northern Georgia but were also observed in other southern states in the United
      States. Resistance to various antibiotics was randomly associated with different
      E. coli RTs. Sarafloxacin resistance was present among different E. coli RTs,
      suggesting that antibiotic usage is not selecting for a clonal population in
      avian E. coli. RAPD provides a rapid and powerful tool to study the epidemiology
      of avian E. coli.

PMID- 9777145
TI  - Postmortem detection of acute septicemia in broilers.
AB  - Septicemia is an unwholesome condition diagnosed during postmortem inspection in
      poultry slaughter establishments on the basis of macroscopic lesions. Early
      identification of septicemia has important public health implications. In this
      study, Pasteurella multocida, Escherichia coli, and Staphylococcus aureus
      septicemia were induced in broilers in order to determine if lesions of acute
      septicemia can be grossly detected in the visceral organs of broiler carcasses
      prior to the development of changes in the skeletal muscle. Increased spleen and
      liver weights were observed during the acute phase of septicemia. Airsacculitis,
      pericarditis, and perihepatitis were observed during the acute phase of P.
      multocida- and E. coli-induced septicemia; and arthritis was the earliest
      indicator of S. aureus-induced septicemia. These macroscopic lesions were
      sufficient to identify unwholesome septicemic broiler carcasses prior to the
      development of changes in the skeletal muscle of the carcass.

PMID- 9777146
TI  - Variability in the resistance of four chicken lines to experimental intravenous
      infection with Salmonella enteritidis phage type 4.
AB  - The capacity of four chicken lines (Y11, L2, B13, PA12) to control Salmonella
      enteritidis (SE) phage type 4 (PT4) systemic colonization was investigated.
      Thirteen-week-old chickens were intravenously inoculated with 10(6) SE colony
      forming units, and the levels of SE colonization were determined at various time
      intervals after inoculation in liver, spleen, genital organs, and ceca. The
      course of SE infection showed a rapid contamination of liver, spleen, and genital
      organs, whereas the ceca were infected later. A significant (P < 0.001) effect of
      the chicken line on levels of SE was detected on day 3 postinoculation (PI) in
      liver and ceca, on day 10 PI in ceca, and on day 15 PI in spleen. Because an
      early control of systemic Salmonella infection by the Ity/Nramp1 gene has been
      demonstrated in mice, we aimed to study the early resistance of chickens to SE.
      As a consequence, we then focused our study on the between- and within-line
      variabilities of SE levels on day 3 PI. According to the SE levels in liver on
      day 3 PI, the chicken lines could be classified as susceptible (Y11 and L2) or
      resistant (PA12 and B13). This early variability was explored in resistant B13
      and susceptible L2 lines. Differences between these two lines were confirmed in
      liver but not in ceca. A large within-line variability was observed in all organs
      of these two lines. The genetic origin of this variability will have to be
      determined as a prerequisite to an eventual selection.

PMID- 9777147
TI  - Restriction fragment length polymorphism analysis of highly virulent strains of
      infectious bursal disease viruses from Holland, Turkey, and Taiwan.
AB  - Strains of highly virulent infectious bursal disease virus (HVIBDV) from Turkey
      (OA, OE), Holland (HOL), and Taiwan (PT, IL) were characterized by reverse
      transcriptase/polymerase chain reaction-restriction fragment length polymorphism
      (RT/PCR-RFLP) analysis and compared with the United States of America (USA)
      classic (STC) and variant (MD, IN) serotype 1 viruses and serotype 2 OH strain. A
      primer pair that amplified a 743-bp fragment of the VP2 gene was used. The RFLP
      profiles of the RT/PCR products were determined with four restriction enzymes
      (SspI, BstNI, MboI, and StyI). The SspI enzyme distinguished the HVIBDVs from the
      USA classic and variant viruses and the serotype 2 virus. The USA serotype 1
      viruses used in this study did not have restriction sites for SspI in the 743-bp
      VP2 fragment. The RFLP profiles of the five HVIBDVs when digested with BstNI were
      different from the USA classic STC virus but were similar to the variant viruses
      (MD, IN). The RFLP profiles for isolates from Turkey and Holland were similar to
      the classic STC strain when digested with MboI but were different from the
      variant USA viruses (MD, IN). The RFLP profiles of the two Taiwan isolates were
      different from the Holland, Turkey, and USA classic and variant viruses when
      digested with MboI. When the five HVIBDVs were digested with StyI enzyme, their
      RFLP patterns were similar to those of the USA classic STC strain but were
      different from the USA variant viruses. None of the strains tested had patterns
      similar to serotype 2 OH virus.

PMID- 9777148
TI  - Simplified sample processing combined with a sensitive nested polymerase chain
      reaction assay for detection of infectious bursal disease virus in the bursa of
      Fabricus.
AB  - A rapid and sensitive protocol for the detection and amplification of infectious
      bursal disease virus (IBDV) RNA in the bursa of Fabricius was developed. By
      digestion with proteinase K and subsequent extraction with phenol and chloroform,
      IBDV RNA was efficiently released from a single bursa. IBDV RNA extraction time
      was shortened to 4 hr, compared with 24 hr with the traditional method, and only
      one bursa was needed instead of five. This more simplified procedure resulted in
      a significant reduction in costs due to less labor and the reduction in expensive
      chemicals and reagents. Four primers were selected from the sequence of a
      hypervariable region in VP2 genes. For the amplification of genomic IBDV RNA, the
      product (643 bp) of reverse transcriptase-polymerase chain reaction (RT-PCR) was
      reamplified and double checked by a nested PCR amplifying a 491-bp cDNA. The
      sensitivity of nested PCR was at least 100 times greater than RT-PCR as
      determined by dilution of the bursal homogenate. The fidelity of the nested PCR
      product was confirmed by Southern blotting, demonstrating specificity to the VP2
      gene of IBDV. The simplified sample processing, shortened procedure time, and
      technical ease of this nested PCR render it more suitable for implementation in
      routine RT-PCR with restriction fragment length polymorphism testing for the
      detection and differentiation of IBDV RNA, especially for studies of IBDV
      infections of individual chickens.

PMID- 9777149
TI  - Molecular characterization of the hemagglutinin gene and oral immunization with a
      waterfowl-origin avian influenza virus.
AB  - Vaccination against highly pathogenic (HP) subtypes of avian influenza (AI) virus
      in poultry has been prohibited in the United States. Recently, policy has been
      changed to potentially allow use of inactivated vaccines in emergency programs to
      control HP H5 and H7 AI. Vaccination with inactivated virus against non-highly
      pathogenic AI viruses has been allowed in the U.S. turkey industry since 1979 (1)
      but requires expensive handling of individual birds for parenteral inoculation.
      Oral immunization would provide a less expensive method to protect commercial
      poultry from AI. Prime candidates for oral vaccines are waterfowl-origin (WFO)
      isolates, which have a tropism for the alimentary tract. One WFO isolate,
      A/mallard/Ohio/556/1987 (H5N9) (MOh87), was characterized by determining the
      complete nucleotide sequence of its hemagglutinin (HA) gene. The HA protein of
      this isolate possessed a deduced amino acid sequence nearly identical to the
      consensus amino acid sequence for all published H5 genes, indicating that it has
      potential as a broadly effective vaccine. Experimental results demonstrated
      measurable serum antibody responses to orally delivered live and inactivated
      preparations of MOh87. Oral vaccination also protected chickens from diverse,
      lethal H5 AI virus challenge strains and blocked cloacal shedding of challenge
      virus.

PMID- 9777150
TI  - Coding region of segment A sequence of a very virulent isolate of IBDV-
      comparison with isolates from different countries and virulence.
AB  - We determined the sequence of the coding region of segment A, coding for the
      viral proteins (VPs) VP2, VP4, and VP3, of a very virulent (vv) infectious bursal
      disease virus (IBDV) isolated in Israel and named IBDVks. We compared the deduced
      amino acid sequences of the proteins of the new isolate with those of the same
      proteins from several IBDV isolates, as published in recent years. The amino acid
      sequences of VP3 and VP4 of the Israeli isolate were 1.9%-2.3% different from the
      sequences of their counterparts from classical strains. Thus, the stable region
      of VP2 of IBDVks was very similar (0-0.68% difference) to the same region of VP2
      from vv strains from Europe and Japan but distinct from that of proteins from
      classical strains from Europe, the United States, and Australia (up to 9.42%
      divergence), showing that IBDVks is more closely related to the vv strains from
      Europe and Japan. We found that viruses isolated in recent years resemble each
      other more than isolates from the same areas isolated a few years earlier. Hence,
      IBDVks can be categorized in one group with vv new isolates from Europe and
      Japan. This group has been found to be distinct from new isolates in the United
      States and strains isolated before the IBDV epidemic during the late 1980s.

PMID- 9777151
TI  - Biological and molecular characterization of Newcastle disease virus (NDV) field
      isolates with comparisons to reference NDV strains.
AB  - Fifty-seven Newcastle disease virus (NDV) isolates from chickens, turkeys, a
      rhea, a parrot, and an anhinga were pathotyped and characterized by monoclonal
      antibody (mAb) inhibition profile, elution rate, and hemagglutinin
      thermostability. Nucleotide sequence analysis of portions of the fusion protein
      and matrix protein genes of the parrot isolate was done for comparison with prior
      sequence analysis of the anhinga isolate and NDV reference strains. Seven of the
      43 chicken isolates were recovered from flocks in Canada. The remaining isolates,
      including 11 from turkeys, were isolated in the United States. All isolates
      except that of the anhinga were of low virulence by mean death time in embryos,
      intracerebral pathogenicity index, and/or intravenous pathogenicity index
      procedures and were classified as lentogens. The anhinga isolate was more
      virulent than the other strains and was pathotyped as a mesogen. However,
      nucleotide sequence analysis of the anhinga isolate had revealed a homology with
      the virulent cormorant isolates of 1992 rather than the classical U.S. mesogens
      characterized by the Roakin strain. Variability was evident among the lentogenic
      isolates. Two isolates from turkeys had mAb profiles that differed from B1 and La
      Sota reference and vaccine strains, and 38% (21/56) of the isolates had more
      thermostable hemagglutinins than those reference strains. There was no evidence
      that any of the isolates from poultry were more virulent than the lentogenic
      pathotype.

PMID- 9777152
TI  - Evaluation of a competitive ELISA for detection of antibodies against avian
      influenza virus nucleoprotein.
AB  - A competitive enzyme-linked immunosorbent assay (C-ELISA) employing a baculovirus
      expressed recombinant nucleoprotein and a monoclonal antibody was developed for
      the detection of antibodies to type A influenza virus nucleoprotein. The
      performance of the C-ELISA was evaluated by testing 756 chickens, 1123 turkeys,
      707 emus, and 1261 ostriches, for a total of 3847 serum samples. Relative to the
      agar gel immunodiffusion (AGID) test, the C-ELISA had a sensitivity of 100% for
      all four species. The C-ELISA's sensitivity relative to the hemagglutination
      inhibition (HI) test results was 100% for chicken, turkey, and emu and 96.2% for
      the ostrich serum samples. More than 90% of the AGID-negative/C-ELISA-positive
      serum samples were found positive by HI for at least one influenza serotype. The
      specificity of C-ELISA relative to AGID ranged from 85.5% to 99.8% for sera
      collected from these species. These results indicated that the C-ELISA was more
      sensitive and more specific than the AGID test and as sensitive and as specific
      as the HI test. The C-ELISA has the potential to replace the AGID test for
      screening sera from avian species, including ratites, for detection of antibodies
      to type A influenza virus.

PMID- 9777153
TI  - Hematologic and plasma chemistry values in captive psittacine birds.
AB  - Reference values for some hematologic parameters in 19 species and plasma
      chemical values in 11 species of Psittacine birds, including cockatoos, parrots,
      amazons, macaws, conures, and lories, were established for use in veterinary
      medicine. The following parameters were studied: hematocrit, hemoglobin
      concentration, erythrocyte number, mean corpuscular volume, mean corpuscular
      hemoglobin, mean corpuscular hemoglobin concentration, erythrocyte dimensions,
      leukocyte number and differential leukocyte count, glucose, urea, uric acid,
      cholesterol, triglycerides, creatinine, aspartate aminotransferase, alanine
      aminotransferase, alkaline phosphatase, creatinine phosphokinase, lactic
      dehydrogenase, gamma glutamyl transpeptidase, total plasma protein, albumin,
      globulins, albumin-globulin ratio, sodium, potassium, calcium, magnesium, total
      phosphorus, chloride, and osmolality. Hematologically, the Psittacine is a very
      homogeneous avian group, with small differences between species. They are,
      however, different from other groups of birds.

PMID- 9777154
TI  - Changes in microflora of the cloaca and oviduct of hens after intracloacal or
      intravaginal inoculation with Salmonella enteritidis.
AB  - Quantitative and qualitative microbiological examination was carried out on
      cloacal and oviductal contents pre- and postinfection with Salmonella enteritidis
      (SE) intracloacally or intravaginally. Before inoculation with SE, the means +/-
      standard deviation (SD) of total bacterial counts, anaerobic bacterial counts,
      and aerobic bacterial counts in the cloaca were log10 7.7 +/- 0.7, 7.4 +/- 0.2,
      and 6.9 +/- 0.8 colony-forming units (CFU)/g, respectively. The predominant
      bacteria were Bacteroidaceae, Lactobacillus, and Escherichia coli. Before
      inoculation with SE, the means +/- SD of total bacterial counts, anaerobic
      bacterial counts, and aerobic bacterial counts in the vagina were log10 5.7 +/-
      1.4, 5.5 +/- 1.3, and 3.6 +/- 2.7 CFU/g, respectively. Bacteroidaceae and
      Lactobacillus were predominant. Following inoculation with SE, only the cloacal
      population of Lactobacillus in hens inoculated intracloacally was significantly
      increased compared to that before the inoculation. Other indigenous microflora
      were stable even after the inoculation. In the uterus, very few bacteria,
      Lactobacillus and Staphylococcus, were isolated. Five of 20 eggs (25%) from hens
      inoculated with SE intravaginally were positive for SE, whereas no SE was
      recovered from 22 eggs in hens inoculated with SE intracloacally. SE was
      recovered from the uterus after intravaginal inoculation with SE and from the
      vagina after intracloacal inoculation with SE. Contamination may ascend from the
      cloaca into the lower parts of the oviduct and subsequently contaminated eggs may
      occur.

PMID- 9777155
TI  - Resistance to Salmonella enteritidis organ invasion in day-old turkeys and
      chickens by transformed T-cell line-produced lymphokines.
AB  - We previously reported an increased resistance to Salmonella enteritidis (SE)
      organ invasion in chicks and turkey poults injected prophylactically with SE
      immune lymphokines (ILK). In the present study, concanavalin A (Con-A)-activated
      splenic T cells isolated from SE-hyperimmunized hens were transformed in vitro
      with reticuloendotheliosis virus strain T (REV-T) (chicken syncitial virus).
      These transformed T cells were then maintained as a long-term (> 1 yr) cell line
      for the harvest of immune lymphokines (VILK). The efficacy of VILK to protect
      turkey poults and chicks against SE organ invasion and the correlation between
      organ invasion and peripheral blood heterophilia were then evaluated. Three
      groups of day-old poults and chicks were injected intraperitoneally with either
      phosphate-buffered saline (PBS; group A), ILK (group B), or VILK (group C).
      Thirty minutes postinjection, poults and chicks were challenged per os with 5 x
      10(5) colony-forming units (CFU) SE and 5 x 10(4) CFU SE, respectively. At 24 hr
      posttreatment, birds in groups A, B, and C were euthanatized and liver samples
      were cultured for the presence of SE. Both the VILK- and ILK-treated turkeys and
      chicks had significant reductions in organ invasion when compared with the PBS
      injected controls (P < 0.005). For peripheral blood studies, turkeys and chicks
      were treated as above, and at 4 hr post-PBS, ILK, or VILK injection; total and
      differential peripheral blood counts were performed on birds from each group. A
      significant (P < 0.05) peripheral blood heterophilia at 4 hr postinjection was
      observed in the ILK- and VILK-treated birds, with no such increase found in the
      PBS-injected group. Correlation analysis revealed a direct relationship between
      the peripheral blood heterophilia in turkeys and chicks seen at 4 hr
      postinjection and the reduction in SE organ invasion seen in the VILK and ILK
      treatment groups (r = 0.991, r = 0.91, respectively). T cells isolated and
      transformed from nonimmune chickens did not produce factors that protected chicks
      from SE organ invasion and did not cause the peripheral blood heterophilia
      observed with ILK and VILK. These results show that the virally transformed SE
      immune T-cell line produces lymphokines that result in the same level of
      peripheral blood heterophilia as ILK and was equally protective against SE organ
      invasion as ILK.

PMID- 9777156
TI  - Detection of duck enteritis virus by polymerase chain reaction.
AB  - Duck enteritis virus (DEV), a herpesvirus, is the causative agent of duck viral
      enteritis in free-flying, feral, and domesticated members of the Anatidae family.
      HindIII-digested DEV DNA was cloned into the plasmid pBluescript, and a 1.95-kb
      fragment was sequenced. This fragment codes for the 3' region of the DEV
      homologues of varicella-zoster virus (VZV) open reading frame (ORF) UL6 and the
      5' region of VZV UL7. Alignment of the putative peptide fragments for DEV UL6 and
      UL7 showed a 64% and 37% identity with VZV UL6 and UL7, respectively. Primers
      located in the highly conserved domain of the UL6 gene were used for a polymerase
      chain reaction (PCR) assay, which was able to amplify DEV DNA. The PCR assay also
      amplified DEV DNA from the original outbreak samples and/or after passage in
      Muscovy duck embryos.

PMID- 9777157
TI  - Diet and humoral responsiveness of lines of chickens divergently selected for
      antibody response to sheep red blood cells.
AB  - Growth and humoral immune response were studied in lines of white leghorn
      chickens selected for high (HA) or low (LA) 5-day antibody titers to an i.v.
      inoculation with 0.1 ml of a 0.25% suspension of sheep red blood cells (SRBC)
      antigen(s). Chicks were fed either a high (E) or low (A) nutrient density diet
      from hatch onward. Chicks from each line-diet subclass were inoculated i.v. with
      0.1 ml of either 0.25% or 2.50% suspension of SRBC at either 7, 14, 21, or 28
      days of age. Antibody titers were measured 5, 10, and 20 days after inoculation.
      LA chicks were heavier than HA chicks at 7 days of age and thereafter. Chicks fed
      diet E were heavier than those fed diet A. Feed efficiency was influenced by diet
      (E > A) at 21 and 28 days of age and line (LA > HA) at 28 days of age. In all but
      one case, antibody titers to SRBC were higher in HA than LA chicks. Also, the
      frequency of nonresponders of chicks inoculated with SRBC at 7 days of age was
      higher for LA than HA chicks. The higher dosage elicited greater 5-day antibody
      responses in LA but not in HA chicks inoculated at 28 days of age. Dietary
      effects on SRBC antibody were generally unimportant except for occasional
      interactions of dosage and line.

PMID- 9777158
TI  - Vaccination of chickens against Ornithobacterium rhinotracheale infection.
AB  - Vaccination of young broilers with inactivated vaccines against experimental
      Ornithobacterium rhinotracheale challenge was found to be effective, but the
      results of vaccination were influenced, in a negative way, by the presence of
      maternal antibodies. The use of a strong adjuvant, such as mineral oil, in a
      bacterin was necessary to obtain good protection when maternal antibodies were
      present. Vaccination of broiler breeders resulted in high serologic responses and
      protection of their progeny against experimental O. rhinotracheale challenge up
      to an age of 4 wk. Vaccination of broilers with a live vaccine was found to be
      effective when the maternal antibody levels were low. A combination of
      vaccinating the breeders with a bacterin and their progeny with a live vaccine at
      approximately 3 wk of age seems to be the best way to protect broilers against O.
      rhinotracheale infection.

PMID- 9777160
TI  - Reduction of fecal shedding and egg contamination of Salmonella enteritidis by
      increasing the number of heterophil adaptations.
AB  - Serial passage of Salmonella enteritidis (SE) in chicken heterophils resulted in
      heterophil-adapted SE (HASE). We now report that an additional five heterophil
      passages have further reduced the number and frequency of fecal shedding of HASE.
      Eleven-times HASE (11 x HASE) given to 12 laying hens for three consecutive days
      reduced fecal shedding of 11 x HASE to three isolations from fecal samples during
      the 70-day postexposure observation period. Hens were exposed to challenge SE 74
      days after treatment with 11 x HASE. Three of 12 11 x HASE-treated hens were
      positive for challenge SE (11/396 fecal samples, or 2.8%) between days 5 and 40
      postchallenge, whereas all 12 challenge control birds were positive (118/420
      fecal samples, or 28.1%) for SE. None of 12 11 x HASE-treated hens was fecal
      positive from day 9 postchallenge, whereas 10 of 12 challenge control hens
      (82/372 fecal samples, or 22.0%) remained positive until day 40, the termination
      of the experiment. None of 525 eggs and eggshells cultured after 11 x HASE
      exposure was positive for Salmonella, and none of 422 eggs and eggshells cultured
      after challenge SE exposure was positive for Salmonella. Eggs or eggshells from
      challenge control hens were positive for Salmonella in 12/479 (2.5%) cases after
      challenge SE exposure.

PMID- 9777159
TI  - Use of Aviguard and other intestinal bioproducts in experimental Clostridium
      perfringens-associated necrotizing enteritis in broiler chickens.
AB  - Clostridium perfringens-associated necrotic enteritis (CPANE) is a common problem
      among rapidly growing broiler strains of chickens that are raised intensively in
      modern microenvironments. The purpose of this study was to compare the use of
      Aviguard and three other intestinal bioproducts (two normal gut flora [NGF]
      products and one probiotic product) in experimental CPANE in broiler chickens.
      Male broiler chicks were housed in the same environmentally controlled facility
      and given one of six treatments. The necrotic enteritis infection model (NEIM)
      used in the present study was effective in inducing CPANE intestinal gross
      lesions in broiler chickens. Equally important, Aviguard was found to be
      significantly more effective than either the other two NGF products or the
      probiotic for reducing gross lesions induced by the NEIM. In addition,
      Aviguard/NEIM-treated chicks ate more feed and had better feed efficiency than
      their NGF- or probiotic/NEIM-treated counterparts. Other significant differences
      among these four reconstituted microbial preparations were not found. Results
      from this study have additional importance because they further support the use
      of reconstituted microbial preparations as novel and effective alternatives to
      antibiotics that can reduce the severity of C. perfringens-associated necrotic
      enteritis challenge in broilers.

PMID- 9777161
TI  - Inclusion body tracheitis associated with avian adenovirus in turkeys.
AB  - Nine turkey flocks with basophilic intranuclear inclusion bodies, suggestive of
      adenovirus, within the epithelial cells of the tracheal mucosa were studied.
      Respiratory signs and increased mortality occurred in turkeys between 6 and 10 wk
      of age from nine commercial turkey meat flocks in central California. Necropsy
      findings included tracheitis and occasional mild sinusitis. Histopathology of the
      tracheas revealed epithelial deciliation, squamous metaplasia, large basophilic
      intranuclear inclusion bodies within epithelial cells, and lymphoplasmatic
      inflammation in the mucosa. Electron microscopy of the mucosa revealed hexagonal
      viral particles, approximately 73 nm in diameter, consistent with adenovirus
      within the nuclei of epithelial cells. All tracheal sections were negative for
      adenovirus group II by specific immunoperoxidase staining. Adenovirus group I was
      isolated from the trachea. In addition, Bordetella avium, Ornithobacterium
      rhinotracheale, and Klebsiella pneumoniae were isolated from the tracheas of
      three, three, and two flocks, respectively. Statistically greater total mortality
      and a smaller percentage of marketed turkeys were observed in the submitted
      flocks than in randomly selected flocks. No significant difference was observed
      between the two turkey groups in market weight, feed conversion, or percentage of
      grade "A" turkeys.

PMID- 9777162
TI  - Impaction of the stomachs in farmed ostriches (Struthio camelus) in Botswana.
AB  - Impaction of the proventriculus, gizzard, and sometimes intestines due to sand
      was confirmed at postmortem in 25 cases involving ostriches (Struthio camelus).
      Although there was no age predisposition, impaction was more common in juvenile
      over 3 mo old. Clinical signs included sternal recumbency, outstretched neck,
      debility, and inability to stand. Palpation of the impacted stomachs gave a
      gritty sensation. Depletion of coronary fat was a consistent postmortem finding.
      The most common material causing impaction was sand. This report highlights
      impaction as one of the major causes of debility and death in intensively farmed
      ostriches. High levels of alkaline phosphatase coupled with low levels of plasma
      glucose, protein, and albumin detected in impacted ostriches may be useful
      diagnostic antemortem indicators of the syndrome.

PMID- 9777164
TI  - Histology, immunohistochemistry, and ultrastructure of hydropericardium syndrome
      in adult broiler breeders and broiler chicks.
AB  - Ten 250-day-old broiler breeders, seven 16-day-old broiler chicks, and three 25
      day-old broiler chicks suffering from hydropericardium syndrome (HPS) in Japan
      were examined histologically, immunohistochemically, and ultrastructurally.
      Clinically, the chickens died suddenly without apparent signs. The mortality
      rates were 6.4%, 20.2%, and 26.1%, respectively. The common characteristic
      histologic lesion was necrosis of hepatocytes, accompanied by intranuclear
      inclusions of hepatocytes and hemorrhages. In the spleen, there were activation
      of macrophages in splenic sinus and ellipsoids and erythrophagocytosis in the
      splenic sinus. The interlobular interstitium of the lung showed marked edema. The
      air and blood capillary areas of parabronchi included many macrophages with
      yellow pigments. With immunoperoxidase staining, intranuclear inclusion bodies
      within degenerating hepatocytes stained positively for group I adenovirus
      antigen. Ultrastructurally, numerous viral particles (65-70 nm in diameter) were
      demonstrated in the intranuclear inclusions of hepatocytes. Group I adenovirus
      (serotype 4) was isolated from liver samples of adult broiler breeders and
      broiler chicks with HPS. This study suggests that HPS may be caused by group I
      adenovirus.

PMID- 9777163
TI  - Encephalomalacia associated with vitamin E deficiency in commercially raised
      emus.
AB  - Thirteen of 64 emus on a commercial emu farm in Ohio exhibited neurological signs
      that included backward staggering, incoordination, generalized weakness, and
      sitting on their hocks with head retracted backward. Eight of the birds showing
      such signs were found dead. Two of these emus were necropsied, and no significant
      gross lesions were observed. Major histopathological lesions were found in the
      cerebellum and included multiple malacic foci in association with neuropil
      rarefaction and astrogliosis within the white matter of folia. In addition, the
      hepatic vitamin E level of one emu was determined at the Michigan State
      University Animal Health Diagnostic Laboratory (MSU-AHDL) to be 14.61
      micrograms/g dry weight. This vitamin E level was in the lower percentile (35%)
      of 30 emu liver samples examined at MSU-AHDL. A diagnosis of vitamin E-associated
      encephalomalacia was made based on clinical signs, gross and histological
      lesions, and liver vitamin E levels.

PMID- 9777166
TI  - Specific treatment of the neuroleptic malignant syndrome.

PMID- 9777165
TI  - Isolation of Georgia variant (Georgia isolate 1992) infectious bronchitis virus
      but not Ornithobacterium rhinotracheale from a Kentucky broiler complex.
AB  - Integrated broiler production operations in western Kentucky have been very
      successful. The reason for this success includes the fact that flocks are free of
      many endemic diseases for a period of time, often years, because birds are raised
      in virgin, disease-free territory. This case report documents that importation of
      birds from an area with endemic Georgia variant (GA-92) infectious bronchitis
      virus and Ornithobacterium rhinotracheale (ORT) bacterial infection resulted in
      introduction of GA-92, but not ORT, to Kentucky farms. As more broiler production
      units locate in western Kentucky, in the early phases of operation, they may not
      experience the "virgin territory," disease-free advantage.

PMID- 9777167
TI  - In vivo neurochemistry of the brain in schizophrenia as revealed by magnetic
      resonance spectroscopy.
AB  - Magnetic resonance spectroscopy (MRS), an application of the methods of nuclear
      magnetic resonance (NMR), is a functional imaging modality that provides a view
      of localized biochemistry in vivo. A number of studies applying MRS to the
      neurochemistry of schizophrenia have been reported, which encompass a range of
      patient populations, states of medication, anatomic regions, nuclear species, and
      MRS techniques. A brief review of the history and methodology of NMR and MRS is
      presented. Comparison is made of MRS capabilities with other functional imaging
      modalities. Aspects of the neurochemistry of schizophrenia relevant to MRS
      studies are reviewed, as are the reported MRS studies involving patients with
      schizophrenia. Areas of consistent findings include decreased phosphomonoesters
      and increased phosphodiesters in frontal lobes, and decreases in the putative
      neuronal cell marker, N-acetylaspartate, in temporal lobes. Studies of
      neurotransmitters such as glutamate, gamma-aminobutyric acid, and glutamine have
      generated inconsistent results. New insights into alterations in neurochemistry
      in schizophrenia have been provided by MRS. Studies of neurotransmitters have
      future potential with improvements in field strength and in spectral editing
      techniques. MRS has the potential to measure brain medication levels and
      simultaneous effects on neurochemistry. MRS may assist in characterizing high
      risk populations, and ultimately guide medication use.

PMID- 9777169
TI  - Corpus callosum shape and size in male patients with schizophrenia.
AB  - BACKGROUND: Corpus callosum (CC) morphology has recently been investigated in
      schizophrenia using refined imaging and analytic techniques; however,
      methodological problems and small sample sizes have led to inconsistent findings.
      METHODS: This study used a large sample of male schizophrenics (n = 79) and male
      controls (n = 65) to investigate size and shape of the CC on midsagittal magnetic
      resonance images. Size was determined by tracing the area of the CC, and shape
      was determined using a landmark-based analysis. In addition, the relationship
      between CC morphology and phenomenologic variables such as age of onset, length
      of illness, exposure to medications, and symptom severity was explored. RESULTS:
      After controlling for age, height, and parental socioeconomic status, there was a
      main effect of diagnosis on CC size (F = 5.05, df = 1,139, p < .03), with
      patients' CCs being significantly smaller. No difference was found between
      patients and controls in CC shape (F = 1.07, df = 18,125, p > .38) or orientation
      (F = 0.79, df = 18,125, p > .70), using a landmark-based technique. Finally,
      there was a significant inverse correlation between size of CC and severity of
      negative symptoms. CONCLUSIONS: These findings support previous studies that have
      found a decrease in size of the CC in patients with schizophrenia. Moreover, the
      decrement in volume is generalized, not regional, and is related to the severity
      of negative symptoms.

PMID- 9777168
TI  - 31Phosphorus magnetic resonance spectroscopy of the dorsolateral prefrontal
      region in schizophrenics--a study including 50 patients and 36 controls.
AB  - BACKGROUND: In a preliminary study we found decreased phosphodiester (PDE)%
      values and an increased phosphomonoester (PME)/phosphodiester ratio in the
      dorsolateral prefrontal region (DLPFR) of 13 chronic schizophrenics vs. 14
      controls using 31phosphorus magnetic resonance spectroscopy (31P-MRS). Since
      these results are in contrast to the findings of other groups, we increased our
      study group to a total of 50 chronic schizophrenics on stable neuroleptic
      medication and 36 controls to minimize the possibility of a chance result due to
      small sample size. METHODS: An image-selected in vivo 31P-MRS method on a Philips
      Gyroscan ACS II scanner working at 1.5 T was used. RESULTS: We could confirm our
      earlier findings of decreased PDE% levels in schizophrenics. Additionally, we
      found phosphocreatine (PCr)% and PCr/adenosine triphosphate (ATP) to be increased
      in the schizophrenics. While no association between PME% and PDE% with
      neuroleptic medication was found, ATP% correlated positively and PCr/ATP
      negatively with the chlorpromazine equivalent dose. CONCLUSIONS: The decreased
      PDE% levels might be characteristic only for chronic, neuroleptic-treated
      patients. The finding of altered high-energy phosphate levels can be interpreted
      as an indication of decreased energy-demanding processes in the DLPFR of the
      investigated patients compared to controls.

PMID- 9777170
TI  - Hemispheric asymmetry of frontal and temporal gray matter and age of onset in
      schizophrenia.
AB  - BACKGROUND: Investigators have reported lack of normal asymmetry of
      lateralization in some schizophrenic patients, as measured postmortem and by
      preference and/or performance. It has been suggested that this lack of asymmetry
      is related to early onset of schizophrenia. The present study extends the inquiry
      by magnetic resonance imaging (MRI) measurement of volumetric asymmetry. METHODS:
      Hemispheric asymmetry of volume in regional gray matter was examined in 16
      schizophrenic patients who had undergone MRI of brain volume. RESULTS: Low levels
      of hemispheric asymmetry in the frontal and temporal areas were strongly
      associated with early onset of schizophrenia, the association with frontal volume
      being more marked than with temporal volume. No relationship was found in the
      other brain areas that were scanned. The findings were not artifacts of
      chronological age, nor of extreme scores in a small sample. CONCLUSIONS: These
      findings are consistent with the hypothesis that failure to develop asymmetry is
      an important component of the pathology underlying some forms of schizophrenia.

PMID- 9777171
TI  - Temporal horn enlargement is present in schizophrenia and bipolar disorder.
AB  - BACKGROUND: Ventricular enlargement and temporal lobe volume deficits have been
      demonstrated in patients with affective disorder as well as those with
      schizophrenia. This study compares quantitative measures of temporal lobe,
      hemispheric, and ventricular volumes in a group of patients with chronic
      schizophrenia and bipolar disorder and seeks to determine if the groups can be
      differentiated on the basis of measured brain abnormalities. METHODS: A series of
      coronal magnetic resonance imaging sections were acquired and analyzed for each
      of 22 patients with chronic schizophrenia, 14 patients with bipolar disorder, and
      15 community volunteers. Eleven regions of interest for each brain were defined,
      which included temporal lobe, superior temporal gyrus, hemisphere, lateral
      ventricle, third ventricle, and temporal horn measures. Tissue measures were
      obtained by tracing, and cerebrospinal fluid measures were obtained by fluid
      tissue thresholding using specialized computer software. RESULTS: Both patient
      groups had significantly larger temporal horn volumes in comparison with the
      control group both before and after correction for intracranial volume. The two
      patient groups did not differ from each other or controls on any other tissue or
      fluid measure. CONCLUSIONS: This study confirms the findings of increased
      temporal horn volume in patients with schizophrenia and suggests that this
      structural abnormality does not differentiate the structural neuropathology of
      schizophrenia from that of bipolar disorder.

PMID- 9777172
TI  - Comparison of glutamate and gamma-aminobutyric acid uptake binding sites in
      frontal and temporal lobes in schizophrenia.
AB  - BACKGROUND: Theories of schizophrenia proposing deficiencies of amino acid
      [glutamate, gamma-aminobutyric acid (GABA)] neurons are in accord with the
      observed temporal lobe pathology of the disease rather than with the newer theory
      of glutamate hyperinnervation and hyperfunction in areas of prefrontal cortex.
      This study addresses the issue by measuring specific uptake sites as indices of
      glutamatergic and GABAergic neuron densities in frontal and temporal lobes.
      METHODS: Frontal cortex (six areas) and temporal lobe (six areas of cortex,
      amygdala, and hippocampus) were dissected from 19 control autopsy brains and 12
      brains from neuroleptic drug-treated schizophrenic patients. Groups had similar
      ages, postmortem intervals, and storage times. Membranes, prepared from tissue
      homogenates, were incubated with D-[3H]aspartate to measure neuronal and glial
      glutamate uptake site binding in 14 areas and with [3H]nipecotic acid to measure
      neuronal GABA uptake site binding in 11 areas. RESULTS: Glutamate and GABA uptake
      sites were not reduced in prefrontal and temporal areas. Instead, we found small
      increases in glutamate uptake sites in prefrontal areas. Some tendency toward
      increased GABA uptake sites were not disease-related. CONCLUSIONS: Our findings
      concur with other studies that propose locally overabundant glutamate systems in
      prefrontal cortex in schizophrenia. Losses of amino acid neurons do not accompany
      the temporal lobe pathology.

PMID- 9777173
TI  - Inositol levels are decreased in postmortem brain of schizophrenic patients.
AB  - BACKGROUND: A previous study reported decreased levels of inositol in frontal
      cortex of postmortem brain from bipolar patients and suicide victims. The aim of
      the present study was to test the specificity of this finding. METHODS: Inositol
      and the enzyme that synthesizes it, inositol monophosphatase, were measured in
      postmortem brain tissue from frontal and occipital cortex and cerebellum from 10
      schizophrenic patients and the previously reported controls. Inositol levels were
      assayed gas-chromatographically as trimethylsilyl derivatives with mannitol as an
      internal standard. Inositol monophosphatase activity in brain homogenates was
      measured as the difference between phosphate release from inositol-l-phosphate in
      the absence and in the presence of Li+. RESULTS: Inositol was significantly
      reduced in all three areas in the schizophrenic patient' brains: inositol
      monophosphatase was unchanged. Postmortem interval did not correlate with
      inositol levels and did not differ between control group and schizophrenic
      patients. CONCLUSIONS: These results suggest an abnormality of second messenger
      precursor availability in common with schizophrenia and affective
      psychopathology.

PMID- 9777175
TI  - Low frontal electroencephalographic coherence in neuroleptic-free schizophrenic
      patients.
AB  - BACKGROUND: Electroencephalographic (EEG) coherence analysis is a noninvasive
      technique for studying corticocortical associations. As there is evidence for a
      dysfunction of the prefrontal dorsolateral cortex in schizophrenia, we
      hypothesized to find lower frontal EEG coherence in schizophrenia. METHODS: EEG
      amplitude and coherence analysis was performed in 16 antipsychotic-free
      schizophrenic patients and 16 healthy controls. EEG recordings were done with 19
      gold-plated electrodes placed according to the International 10/20 system against
      averaged signals from both earlobes. Local coherence was computed for 22 adjacent
      electrode pairs within the hemispheres and interhemispheric coherence for eight
      corresponding electrode pairs of both hemispheres in the delta, theta, alpha, and
      beta-I band. RESULTS: Amplitude and interhemispheric coherence analysis revealed
      no differences. Local EEG coherence was significantly lower in schizophrenic
      patients for Fpl-F7 in the delta (p = .001) and the theta band (p = .002), and at
      F7-F3 in the alpha band (p = .002). In the delta band coherence of Fpl-F7 was
      inversely correlated to the Positive and Negative Syndrome Scale positive
      symptoms subscore (R = -.74, p = .014). CONCLUSIONS: Assuming that EEG coherence
      can be used to index functional coupling between brain areas under the
      electrodes, the low EEG coherence in Fpl-F7 and F7-F3 in schizophrenic patients
      might reflect impaired information processing in the left dorsolateral prefrontal
      cortex.

PMID- 9777174
TI  - Cerebrospinal fluid inositol monophosphatase: elevated activity in depression and
      neuroleptic-treated schizophrenia.
AB  - BACKGROUND: Inositol monophosphatase (IMPase) is a key enzyme in the regulation
      of the activity of the phosphatidyl inositol (PI) signaling pathway. This enzyme
      is also found in the cerebrospinal fluid (CSF), where it may prove useful as a
      marker of dysfunctional PI signal transduction. METHODS: IMPase activity was
      measured in lumbar CSF of depressed and neuroleptic-treated schizophrenic
      patients. In addition, and to gain an insight into the factors that influence the
      levels of CSF IMPase, enzyme activity was measured in subgroups of schizophrenic
      patients treated for 3-7 days with lithium or 7 days with inositol. RESULTS: CSF
      IMPase activity was significantly increased by 88% in depressed and by 172% in
      schizophrenic patients relative to control subjects. Lithium produced a marked
      increase in CSF IMPase activity in the group as a whole, and this group effect
      could be more specifically attributed to 3 of the 8 individuals in whom enzyme
      activity increased by over 300%. On the other hand, inositol had no effect on CSF
      IMPase activity. CONCLUSIONS: In the absence of a clear relationship between CSF
      IMPase activity and neuronal PI signaling pathways it is not possible to
      correlate these changes with altered neuronal function. Nevertheless, increased
      CSF IMPase activity in depression and schizophrenia may be a marker of the
      pathophysiological processes underlying these disorders. Moreover, the large
      lithium-induced increase in IMPase activity seen in a subgroup of schizophrenic
      subjects suggests a differential regulation of CSF enzyme activity in these
      patients.

PMID- 9777176
TI  - Distinguishing schizophrenic patients from healthy controls by quantitative
      measurement of eye movement parameters.
AB  - BACKGROUND: Eye tracking dysfunction is a putative trait marker for
      susceptibility to schizophrenia; however, it cannot be recommended as an
      additional tool for the diagnosis of schizophrenia, due to low sensitivity and
      specificity. METHODS: To assess the diagnostic potentials of combinations of eye
      movement paradigms, four smooth pursuit experiments (1: constant velocity of 15
      degrees/sec; 2 and 3: combination with either visual or auditory distractors; 4:
      constant velocity of 30 degrees/sec) and two saccadic eye movement experiments
      (1: reflexive saccades; 2: voluntary saccades) were conducted. Fourteen patients
      with residual schizophrenia and 17 healthy controls were studied. Two sets of
      discriminant analyses (each with the resubstitution and with the "leaving one
      out" method) were calculated. RESULTS: In the first set, all 10 characteristic
      variables were included, whereas for the second set, the three most powerful
      parameters were selected (two from smooth pursuit tasks and one from a voluntary
      saccade experiment). This procedure provided the best classification results,
      regarding concordance between clinical diagnoses and eye movement dysfunction
      (kappa = .67-.80). CONCLUSIONS: Schizophrenic patients of the residual subtype
      can be differentiated from healthy individuals with considerable criterion
      validity on the basis of paradigms from two different ocular motor systems.

PMID- 9777177
TI  - The relationship between skin conductance hyporesponsivity and perseverations in
      schizophrenia patients.
AB  - BACKGROUND: It has been reported that approximately 45% of schizophrenia patients
      versus 10% of normal comparison subjects are classified as skin conductance
      hyporesponders (SCOR-HR: the lack of a robust orienting response) when exposed to
      innocuous tones. We studied the skin conductance orienting response (SCOR) of
      schizophrenia patients during the exposure to complex and abstract stimuli. We
      investigated two questions: 1) would the same percentage of schizophrenia
      patients be classified as SCOR-HR when the orienting stimuli are complex and
      abstract as when they are innocuous tones; and 2) whether SCOR-HR schizophrenia
      patients have associated frontally mediated neurocognitive deficits. METHODS:
      Thirty-one schizophrenia patients and 29 normal comparison subjects were
      presented with the Rorschach inkblot test while their SCORs were recorded.
      Schizophrenics were divided in two groups: SCOR-HR and SCOR responders.
      Demographic and clinical comparisons were made between the two groups. Rorschach
      responses were scored for the presence of perseverations. RESULTS: Forty-five
      percent of the schizophrenia patients were classified as SCOR-HR versus 10% of
      the normal comparison subjects. Among the schizophrenia patients, SCOR-HR was
      associated with increased perseverations, which were in turn correlated with the
      Scale for the Assessment of Negative Symptoms scores. CONCLUSIONS: It appears
      that SCOR-HR in schizophrenia is not a function of the "meaningfulness" of the
      stimuli. When SCOR status was combined with the measure of stuck-in-set
      perseverations, a pattern of results emerged lending indirect support to the
      hypothesis that relates SCOR-HR to frontal impairment and to the idea that SCOR
      HR schizophrenia patients may represent a specific subgroup.

PMID- 9777178
TI  - P300 delay and attenuation in schizophrenia: reversal by neuroleptic medication.
AB  - BACKGROUND: P300 amplitude reduction in schizophrenia has been found by many
      investigators, but P300 latency generally has been reported to be normal;
      however, conflicting findings are present in the literature, and interpretation
      has been confounded by medication effects and methodological differences.
      METHODS: This study used a standard auditory oddball paradigm to compare the
      latency, amplitude, and topographic distribution of P300s in neuroleptic-free
      schizophrenic patients with those of healthy controls. The patients then were
      treated for 6 weeks with either remoxipride or haloperidol, and their P300s were
      reassessed. RESULTS: P300s were attenuated and delayed among neuroleptic-free
      patients. There was no evidence of peak lateralization or amplitude asymmetry
      over temporal areas. Subsequent neuroleptic medication normalized P300 latencies
      and increased P300 amplitudes, but the latter remained below normal limits over
      all except frontal areas. There were no correlations between P300 latency or
      amplitude and clinical symptomatology either before or after treatment.
      CONCLUSIONS: The finding of a P300 delay in neuroleptic-free schizophrenics that
      is normalized by neuroleptic medication has not been reported previously.
      Neuroleptic effects on P300 amplitude and latency appear to be independent of
      effects on clinical symptoms, and cannot be attributed to anticholinergic
      activity.

PMID- 9777179
TI  - Predictors of differential response to clozapine and haloperidol. Veterans
      Affairs Cooperative Study Group on Clozapine in Refractory Schizophrenia.
AB  - BACKGROUND: We sought to identify baseline predictors of response to clozapine.
      METHODS: Data were from a 15-site randomized clinical trial comparing clozapine
      and haloperidol in hospitalized patients with refractory schizophrenia (n = 423).
      Three-month outcomes were analyzed with the full sample (n = 368 due to
      attrition). Because of crossovers, analyses of 12-month outcomes were conducted
      with crossovers excluded (n = 291). Clinical predictors included age, race,
      diagnosis (current substance abuse, paranoid subtype of schizophrenia, or
      depressive syndrome), severity of symptoms, quality of life, age at onset of
      schizophrenia, extrapyramidal symptoms, and VA compensation payment. Multiple
      regression analysis was used to examine the interaction of treatment condition
      and each of these variables in predicting outcomes for symptoms, quality of life,
      side effects, and days hospitalized. RESULTS: Patients with higher quality of
      life at baseline (p = .04) and higher symptoms (p = .02) had relatively smaller
      declines in hospital days at 6 months. In the 12-month sample patients with
      higher levels of symptoms had greater symptom reductions at 12 months (p = .03)
      and greater improvement in quality of life (p = .004). CONCLUSIONS: Although high
      levels of symptoms were associated with greater improvement on clozapine, these
      findings are not robust enough to suggest that any specific, clinically defined
      subgroup of refractory patients should be preferentially targeted for clozapine
      treatment.

PMID- 9777180
TI  - Dopamine D4 receptor gene polymorphisms and neuroleptic response in
      schizophrenia.
AB  - BACKGROUND: Dopamine D4 receptor (DRD4) gene polymorphisms are associated with
      various pharmacologic activities. This study investigated whether polymorphisms
      of 48-bp tandem repeats in the exon 3 of the DRD4 gene are related to neuroleptic
      response. METHODS: The neuroleptic response at the acute stage of schizophrenia
      was assessed in 80 (48 men, 32 women) schizophrenic patients. The negative
      symptoms at remission were also rated. DRD4 genotype was established using the
      polymerase chain reaction. Patients with genotypes containing an allele with only
      two repeats (2-2, 2-3, 2-4, 2-6) were assigned to group I (n = 38). Those
      homozygous for four 48-bp repeats were assigned to group II (n = 42). RESULTS:
      Thirteen (34.2%) of the 38 group I subjects and 26 (61.9%) of the 42 group II
      subjects had good neuroleptic response during acute stage treatment (chi 2 6.12,
      df = 1, p < .02). In remission, the rates of negative symptoms of blunt affect,
      avolition, and global negative rating were higher in group I than in group II.
      This was more prominent in men than in women. CONCLUSIONS: The presence of
      homozygous four 48-bp repeats in both alleles in exon 3 of the DRD4 gene is
      associated with good neuroleptic response during acute treatment, and with a
      lower prevalence of negative symptoms at remission, especially in male
      schizophrenic patients.

PMID- 9777181
TI  - Pretreatment plasma homovanillic acid in schizophrenia and schizoaffective
      disorder: the influence of demographic variables and the inpatient drug-free
      period.
AB  - BACKGROUND: The relationship between plasma homovanillic acid (pHVA) and
      schizophrenic symptoms has not been conclusively determined. We reexamine pHVA
      levels in a new sample of patients with emphasis on demographic variables and the
      drug-free period. METHODS: Plasma HVA levels were studied in 54 schizophrenic and
      schizoaffective-disordered, drug-free inpatients suffering from a psychotic
      exacerbation. RESULTS: A significant correlation was observed between pHVA levels
      and the number of inpatient drug-free days in the total sample, as well as the
      schizophrenic patient subsample. Further, pHVA was significantly and positively
      correlated with the duration of illness in the schizophrenic patient subsample.
      Plasma HVA correlations with behavior, as measured by Brief Psychiatric Rating
      Scale factors (anxiety/depression and hostility/suspiciousness), emerged only
      when considering schizophrenic patients drug-free for more than 2 weeks. No
      correlation was found between pHVA and the age of illness onset or the duration
      of the delay of treatment of the first psychotic episode. CONCLUSIONS: The
      effects of antipsychotic withdrawal on levels of pHVA in clinical populations may
      have to be examined and controlled for in future studies attempting to study the
      relationship between this metabolite and behavior in acutely ill, drug-free
      schizophrenic patients.

PMID- 9777182
TI  - Tardive dyskinesia and serum iron indices.
AB  - BACKGROUND: This study was undertaken to evaluate whether peripheral (serum)
      markers of iron status are associated with severity of the choreoathetoid
      movements seen in tardive dyskinesia (TD). METHODS: Serum iron indices (ferritin,
      iron, and total iron binding capacity) and fluphenazine levels were measured in a
      group of 30 male DSM-III diagnosed schizophrenic patients chronically treated
      with fluphenazine decanoate. The severity of choreoathetoid movements was
      assessed with the Abnormal Involuntary Movement Scale (AIMS), and akathisia was
      assessed with the Barnes scale. RESULTS: A significant positive correlation was
      observed between AIMS scores and serum ferritin. This relationship remained
      significant after controlling for age and plasma fluphenazine levels. No
      significant correlations were observed between serum iron or total iron binding
      capacity and choreoathetoid movement ratings. There were no significant
      associations between serum iron indices and akathisia ratings. CONCLUSIONS: The
      data suggest that choreoathetoid movements are associated with serum ferritin
      levels in chronically medicated male schizophrenic patients. This relationship
      does not seem to be caused by an association of these variable with age or plasma
      fluphenazine levels. In addition, the relationship seems to be specific, since
      other iron indices and another extrapyramidal side effect (akathisia) do not
      demonstrate a similar relationship. In view of reports that antipsychotic
      medications change normal iron metabolism and increase iron uptake into the
      brain, the current results could be interpreted to suggest that serum ferritin
      levels may be a risk factor for TD in patients treated with "classic"
      antipsychotic medications.

PMID- 9777183
TI  - Serum iron in catatonia and neuroleptic malignant syndrome.
AB  - BACKGROUND: Preliminary data suggest that decreased serum iron levels predict the
      progression of catatonia to neuroleptic malignant syndrome (NMS). This study
      examines the predictive value of low serum iron in this NMS conversion and
      explores other potential significance of serum iron in catatonia. METHODS: Fifty
      patients with catatonia were prospectively identified at two psychiatric
      intensive care units during a 3-year period [incidence of 5% (39/716) and 13%
      (11/86) respectively]. Serum iron was measured in 39 episodes. Seventeen episodes
      (44%) showed low serum iron levels. A retrospective chart review of patients
      identified was conducted, comparing those with low and normal serum iron levels.
      RESULTS: Low serum iron levels were associated with malignant catatonia, excited
      catatonia, and poor responses to benzodiazepines. There were 7 episodes of
      malignant catatonia. All had low serum iron. Neuroleptic were used in 5 of them,
      and all 5 evolved into NMS. No such NMS conversion was noted in those with normal
      serum iron or in nonmalignant catatonia with low serum iron. Seven episodes (with
      low serum iron) failing benzodiazepine therapy responded subsequently to lithium
      neuroleptic combination therapy. CONCLUSIONS: Malignant catatonia, associated
      with low serum iron, is at high risk of evolving into NMS. Low serum iron in
      nonmalignant catatonia does not predict this NMS conversion. Excited catatonia as
      a catatonic subtype (associated with low serum iron and unfavorable
      benzodiazepine responses) deserves more research attention. There appears to be a
      possible connection between treatment resistance to benzodiazepines, favorable
      responses to lithium-neuroleptic combination, and low serum iron.

PMID- 9777184
TI  - Enhancement of antipsychoticlike properties of raclopride in rats using the
      selective serotonin2A receptor antagonist MDL 100,907.
AB  - BACKGROUND: Selective suppression of conditioned avoidance response (CAR) is a
      standard animal screening test for predicting antipsychotic effect. Ability to
      suppress CAR is presumed to be due to antagonism at dopamine receptors, a
      property shared by all known antipsychotics. METHODS: Using CAR behavior, in a
      conventional shuttle-box paradigm, as an index for antipsychotic efficacy, the
      effects of the selective serotonin2A receptor antagonist MDL 100,907 alone, and
      in combination with the dopamine D2 receptor antagonist raclopride, were studied
      in adult male Sprague-Dawley rats. Nonparametric procedures were employed for
      statistical evaluation. RESULTS: MDL 100,907 (0.1-1.5 mg/kg, SC) alone did not
      suppress CAR in a manner predictive of antipsychotic activity; however, in the
      presence of an ED50 (0.14 mg/kg, SC) dose of raclopride, MDL 100,907 enhanced and
      prolonged the suppression of CAR. In the presence of a subthreshold (0.05 mg/kg,
      SC) dose of raclopride, MDL 100,907 induced a suppression of CAR. CONCLUSIONS:
      The results suggest that treatment with a selective serotonin2A receptor
      antagonist alone may not produce a robust antipsychotic effect; however, a
      selective serotonin2A receptor antagonist in the presence of a minimal dopamine
      D2 receptor blocking action could potentially be an adjunctive therapy resulting
      in improved antipsychotic efficacy and fewer extrapyramidal symptoms.

PMID- 9777186
TI  - [Changes in ultrastructure of axon-spine contacts in the human brain during
      normal aging and in vascular pathology].

PMID- 9777185
TI  - [The role of retroposition in the self-regulation of genome processes (do genes
      program the body and retroposons program genome?].

PMID- 9777187
TI  - [Experimental substantiation of the metasympathetic nervous system condition in
      asthma].

PMID- 9777188
TI  - [Expression of the bone marrow macrophage receptors during cytostatic
      myelosuppression].

PMID- 9777189
TI  - [Effect of seleptin on the reproduction of the active avoidance reaction in
      rats].

PMID- 9777190
TI  - [Effect of cerebral ischemia of various severity on acute seizures and chronic
      epileptogenesis].

PMID- 9777191
TI  - [Bombesin stimulates pancreatic beta-cell function in rats with experimental
      diabetes].

PMID- 9777192
TI  - [Mechanism of the hypocoagulation effect of the laser low energy radiation].

PMID- 9777193
TI  - [Effect of the active immunization to plasma amine oxidase on memory and brain
      mediator activity in rats].

PMID- 9777194
TI  - [Effect of high density lipoproteins and hydrocortisone on apolipoprotein E
      production in Kupffer cells].

PMID- 9777195
TI  - [Mechanism of changes in the platelet functional activity caused by low energy
      laser irradiation].

PMID- 9777196
TI  - [The role of hemoglobin on the regulation of electrokinetic characteristics and
      volume of erythrocytes].

PMID- 9777197
TI  - [Effect of bromocriptin on prolactin receptor expression in liver cells after the
      common bile duct ligation].

PMID- 9777198
TI  - [Effect of the synthetic heparin antagonist--quaternary ammonium salt of 25
      conidine oligomer on the regeneration of liver injured by CCl4].

PMID- 9777199
TI  - [Enhancement of the blood flow in the stenosed carotid artery with high molecular
      weight polyethylene oxide].

PMID- 9777200
TI  - [Oxygen burst in human blood monocytes induced by liposomes with the various
      lipid composition].

PMID- 9777202
TI  - [Membrane-bound dehydrogenases of Gluconobacter oxydans whole cells as basis for
      sensors for determination of sugars, alcohols, and polyols].

PMID- 9777201
TI  - [Microorganism ability to inactivate the bactericidal effect of the thrombocyte
      cationic protein (beta lysin)].

PMID- 9777203
TI  - [Erythropoiesis during bacterial infection].

PMID- 9777204
TI  - [Immune response to plasma lipoproteins induced by C-reactive protein].

PMID- 9777205
TI  - [Effect of arginine vasopressin on the level of cyclic nucleotides,
      phosphorylation of cell proteins, and plastic adhesion of mouse peritoneal
      macrophages].

PMID- 9777206
TI  - [Recovery of the colony-forming activity of of stem hemopoietic and blood cells
      of mice after 1-beta-D-arabinofuranosylcytosine administration].

PMID- 9777207
TI  - [Genetic models of the impairment of the startle reaction pre-impulse
      inhibition].

PMID- 9777208
TI  - [Participation of gastroduodenal mucosa prostaglandins in the anti-ulcer effect
      of venter].

PMID- 9777209
TI  - [Granulocyte colony-stimulating factor production in patients with chronic
      myelosis].

PMID- 9777210
TI  - [Cytochemical and morphologic changes in brain neurons caused by delta sleep
      inducing peptide].

PMID- 9777211
TI  - [Liver cell ultrastructure during exhaustive physical load].

PMID- 9777212
TI  - [Ultrastructural changes in liver sinusoid endothelial cells during treatment of
      long-term crash syndrome with dextran].

PMID- 9777213
TI  - [The role of fibroblast growth factor and transforming growth factor isoforms in
      the development of nephrotoxic nephritis in rats].

PMID- 9777214
TI  - [Morphofunctional characteristics of the rat ovarian capillary bed during low
      intensity laser irradiation].

PMID- 9777215
TI  - [Effects of neo-kyotorphin and delta sleep-inducing peptide on the rectal
      temperature in rats in the norm, during hypothermia and self-warming].

PMID- 9777216
TI  - [Myocardial mast cell reaction during neoangiogenesis induced by YAG:Nd laser].

PMID- 9777217
TI  - [Re-expression of cytokeratin-19 in human hepatocyte primary culture].

PMID- 9777218
TI  - [Natural killer cells and endogenous biological relay].

PMID- 9777219
TI  - [Characteristics of the vascular reactivity in hypertensive NISAG rats].

PMID- 9777220
TI  - [Effects of dipeptides Gly-Pro, Pro-Gly, glycine, and proline on the cardiotropic
      effect of acetylcholine].

PMID- 9777221
TI  - [Vagal regulation of microhemodynamics and oxygen supply of the contractile
      apparatus of the small intestine].

PMID- 9777222
TI  - [Increase of the membrane-bound urokinase level in monocytes from patients with
      atherosclerosis is accompanied by decrease of urokinase-induced myocyte
      migration].

PMID- 9777223
TI  - [Increased blood viscosity syndrome in SHR rats: analysis of the model adequacy].

PMID- 9777224
TI  - [Changes in the morphofunctional state of rat erythrocytes caused by the native
      venom of the red cobra (Naja pallida)].

PMID- 9777225
TI  - [Aggregation and 3H-serotonin release from thrombocytes stimulated by serotonin
      in patients with migraine].

PMID- 9777226
TI  - [Effect of high density lipoproteins on the ADP-induced aggregation of
      thrombocytes in plasma].

PMID- 9777228
TI  - [Transformations of human carboxyhemoglobin molecules induced by ultraviolet
      radiation].

PMID- 9777227
TI  - [Disturbances of proliferative properties of cells in the early embryo impair the
      following development of the nervous, immune, and endocrine systems in the
      offspring].

PMID- 9777229
TI  - [Effects of cattle brain tissue hydrolysates on the protein synthesis in various
      organs of mice and cultured cells].

PMID- 9777230
TI  - [Membranotropic effect of 2-(chloroethoxy)-para-N
      dimethylaminophenylphosphinylacetic acid hydrazide (Kapakh)].

PMID- 9777231
TI  - [Anabolic properties of furostanol glycosides from Dioscorea deltoidea wall].

PMID- 9777232
TI  - [Mechanism of the mildronate effect on the development of rabbit embryos during
      placental insufficiency].

PMID- 9777233
TI  - [Effect of trekrezan on the lipid peroxidation in patients with chronic cardiac
      insufficiency].

PMID- 9777234
TI  - [Immunoenzyme system for detection of antibodies in their complexes with HIV-1
      antigens].

PMID- 9777236
TI  - [Sex steroid hormones and their receptors in pancreatic neoplasms].

PMID- 9777235
TI  - [Monoclonal antibodies against nerve tissue growth protein A3G7 impair learning
      and memory in adult rats].

PMID- 9777237
TI  - [Activity and inducibility of cytochrome p-450-1A in the liver of mice with
      different sensitivity to hepatocarcinogenic effect of o-aminoazotoluene].

PMID- 9777238
TI  - [Lipid composition of erythrocyte membranes in patients with cancer].

PMID- 9777239
TI  - [Effect of the ozonized physiologic solution on biochemical parameters of liver
      during neoplasia].

PMID- 9777240
TI  - [Experimental clinical substantiation of plasma dynamic therapy of wounds with
      nitric oxide].

PMID- 9777241
TI  - [Effect of iodine isotope on the hypophyseal-thyroid and immune systems of
      children residing in radionuclide polluted areas].

PMID- 9777242
TI  - [Colony forming megakaryocyte units in the peripheral blood of patients with
      hyperlipoproteinemia].

PMID- 9777243
TI  - [Effect of implantation of the placental tissue on the morphofunctional condition
      of the rat placenta].

PMID- 9777244
TI  - [Common pathological processes in somatic muscles during genetically determined
      metabolic myopathy in W/SSM rats].

PMID- 9777245
TI  - [Morphofunctional evaluation of the intestinal wound reparation depending on the
      age].

PMID- 9777246
TI  - [Compression ureter anastomoses. Development of technique principles].

PMID- 9777247
TI  - The relationship between adhesion molecules and neuronal plasticity.
AB  - 1. It is presently widely assumed that structural reorganization of synaptic
      architectures subserves the functional gains that define certain neuronal
      plasticities. 2. While target molecules thought to participate in such
      morphological dynamics are not well defined, growing evidence suggests a pivotal
      role for cell adhesion molecules. 3. Herein, brief discussions are presented on
      (i) the history of how adhesion molecules became implicated in plasticity and
      memory processes, (ii) the general biology of some of the major classes of such
      molecules, and (iii) the future of the adhesion molecule/plasticity relationship.

PMID- 9777249
TI  - Low-density induced apoptosis of cortical neurons is inhibited by serum factors.
AB  - 1. We investigated the survival of neurons under serum-free conditions without
      any exogenous signal molecules, using primary cultures of rat cerebral cortex. 2.
      Survival activity, measured with Alamar Blue, showed a cell density dependency
      under serum-free conditions. 3. The addition of fetal bovine serum suppressed the
      apoptotic cell death accompanied by DNA-laddering and fragmentation specific in
      low-density cultures, resulting in the disappearance of the cell density
      dependency of survival. 4. These findings suggest that serum factors may
      substitute for endogenous survival factors from cortical neurons in high-density
      cultures.

PMID- 9777248
TI  - Pyrimidine nucleotide-stimulated thromboxane A2 release from cultured glia.
AB  - 1. Uridine triphosphate (UTP), uridine diphosphate (UDP), cytidine triphosphate
      (CTP), and deoxythymidine triphosphate (TTP) caused concentration-dependent
      increases in the release of thromboxane A2 (TXA2) from cultured glia prepared
      from the newborn rat cerebral cortex. Although each of the pyrimidine nucleotides
      displayed similar potencies, CTP and TTP were considerably less effective than
      either UTP or UDP. The purine nucleotide ATP was equally as potent as the
      pyrimidine nucleotides but was marginally less effective than either UTP or UDP.
      2. The ability of UTP, UDP, TTP, and CTP to promote TXA2 release from cultured
      glia was inhibited in a concentration-dependent manner by suramin and was
      markedly reduced when incubations were performed either in Ca(2+)-free medium or
      on cultures which had been maintained in serum-free growth medium for 4 days
      prior to experimentation. 3. Challenges with UTP and UDP in combination were
      found to elicit a response which was no different from the effects of these
      nucleotides alone; in addition, their effects were reversed by the phospholipase
      A2 inhibitor ONO-RS-082. A slight reduction in UTP- and UDP-stimulated TXA2
      release was observed in cultures grown in the presence of leucine methyl ester, a
      treatment reported to limit microglial survival. 4. These results suggest that
      glia are targets for extracellular pyrimidine nucleotides and that their ability
      to release eicosanoids from these cells may be important in the brain's response
      to damage.

PMID- 9777250
TI  - Interferon yield and MHC antigen expression of human medulloblastoma cells and
      its suppression during dibutyryl cyclic AMP-induced differentiation: do
      medulloblastoma cells derive from bipotent neuronal and glial progenitors?
AB  - 1. Human medulloblastoma (ONS-76), a central nervous system (CNS)-derived
      undifferentiated cell line, was found to possess glial characteristics as defined
      by responses in the interferon (IFN) system; ONS-76 cells produced as much IFN
      beta as human fibroblast and glioma cells by viral infection and poly(I):poly(C)
      induction. 2. Major histocompatibility complex (MHC) class I antigens were also
      induced under IFN-beta stimulation. ONS-76 cells expressed neurofilament protein,
      as shown by Northern blot analysis, and morphological differentiation was induced
      by dibutyryl cyclic AMP (dcAMP). 3. Expression of IFN-beta and MHC class I
      antigens was suppressed in ONS-76 cells during the dcAMP-induced differentiation.
      4. These results showed that ONS-76 cells possessed a glial property in IFN
      system responses and a neuronal property in cytoskeleton protein, suggesting that
      the precursors of medulloblastoma may be characterized as bipotent neuronal and
      glial progenitors in CNS.

PMID- 9777251
TI  - Characterization of the human gonadotropin-releasing hormone receptor
      heterologously produced using the baculovirus/insect cell and the Semliki Forest
      virus systems.
AB  - 1. Two eukaryotic viral systems, the baculovirus/insect cell and the Semliki
      Forest virus systems, were tested for heterologous expression of human
      gonadotropin-releasing hormone receptor (GnRHR) cDNA. 2. An unmodified as well as
      a c-myc epitope-tagged human GnRH receptor was produced in two insect cell lines
      (Spodoptera frugiperda, Trichoplusia ni) after infection with the respective
      recombinant baculoviruses. In both insect cell lines, the receptor was identified
      by immunoblot analysis as a triplet of bands between 35 and 40 kDa. After
      deglycosylation of the receptor the molecular mass decreased to 35 kDa. The GnRH
      receptor was localized in membrane compartments within the infected insect cells.
      However, only in membranes of infected Trichoplusia ni insect cells could
      approximately 2000 receptors per cell be detected. 3. Production of the GnRH
      receptor in BHK cells using the Semliki Forest virus system resulted in
      approximately 50,000 receptors per cell. A maximal yield of 0.42 pmol/mg membrane
      protein was obtained 24 hr after electroporation of BHK cells with in vitro
      synthesized RNA. Binding of the antagonist [125I]Cetrorelix was saturable with a
      KD of 1.3 nM. The receptor produced in the BHK cells was further characterized by
      ligand displacement studies. The rank order of agonist and antagonist affinities
      was Cetrorelix > Triptorelin > Antide > GnRH.

PMID- 9777254
TI  - In vivo signal transduction of tetrodotoxin-sensitive nociceptive responses by
      substance P given into the planta of the mouse hind limb.
AB  - 1. We developed a simple and sensitive peripheral analgesic test in mice. 2.
      Substance P (SP) given into the planta (i.pl.) of the mouse hind limb produced a
      flexor response. The flexor response was dependent on SP doses (0.1-100 pmol,
      i.pl.). When SP (10 pmol) was given every 5 min, there were stable flexor
      responses. These nociceptive responses were completely abolished by CP-96,345, a
      neurokinin 1 receptor antagonist. 3. SP-induced responses were also blocked by
      several signal transduction-related compounds, such as tetrodotoxin, EGTA, and
      U73122, a selective phospholipase C inhibitor. 4. These findings suggest that SP
      depolarizes peripheral nerve endings, possibly through inositol trisphosphate
      (Ins P3)-gated Ca2+ influx, followed by induction of action potentials in the
      peripheral axons of primary afferent neurons.

PMID- 9777252
TI  - Beta-adrenergic receptors mediate a stress-induced decrease in IGF-II mRNA in the
      rat cerebellum.
AB  - 1. Exposure to a combined forced swimming-confinement stress resulted in a
      decrease in insulin-like growth factor II (IGF-II) mRNA levels in the whole brain
      (without the cerebellum) and in the isolated brain areas of the cerebral cortex,
      the hippocampus, and the cerebellum. 2. In an effort to elucidate the
      neurotransmitter systems involved in this stress-induced decrease, animals were
      injected prior to exposure to the stress, with either propranolol, diazepam, or
      MK-801. 3. Administration of diazepam or MK-801 did not affect the stress-induced
      decrease in IGF-II mRNA in any of the three brain areas examined. 4.
      Administration of propranolol prior to the exposure to the stress inhibited the
      stress-induced decrease in IGF-II mRNA in the cerebellum. Propranolol had no such
      effect in the cerebral cortex or the hippocampus. 5. Our results suggest that in
      the cerebellum, the stress-induced decrease in IGF-II mRNA is mediated by beta 2
      adrenergic receptors.

PMID- 9777255
TI  - Social information-processing patterns as predictors of social adaptation and
      behavior problems among maltreated children in foster care.
AB  - OBJECTIVE: The goal of this investigation was to determine if social information
      processing patterns were predictive of later social adaptation and behavior
      problems within a group of maltreated children in foster care. METHOD: A
      longitudinal design was used to address the study hypotheses. The sample
      consisted of 124 maltreated children ages 5 to 10 who had been placed into foster
      care. Twelve months following entrance into foster care, children were presented
      with age-relevant hypothetical vignettes to assess the quality of the way in
      which they process social information. Six to 8 months following this assessment,
      caregivers completed the Vineland Adaptive Scales and the Child Behavior
      Checklist. RESULTS: Measures reflecting unbiased and competent processing were
      predictive of social adaptation, whereas measures reflecting biased and
      incompetent processing were predictive of behavior problems. In aggregate,
      processing measures accounted for a significant proportion of the variance in the
      outcome measures. CONCLUSIONS: The findings suggest that the manner in which
      maltreated children process social information has a bearing on their later
      social adaptation and behavioral adjustment. Therefore, maltreated children in
      foster care may benefit from interventions that target the manner in which they
      process social information.

PMID- 9777256
TI  - School-age and adolescent children's perceptions of family functioning in
      neglectful and non-neglectful families.
AB  - OBJECTIVE: Examined the question, do neglected children's perceptions of their
      own family's functioning acknowledge the differences that exist between
      neglectful and non-neglectful families? METHOD: An inter-rater consistency design
      was used; child and caseworker reports of family functioning in neglectful (n =
      33) and non-neglectful families (n = 34) were compared. RESULTS: After
      establishing significant differences between the socioemotional and physical
      environment provided by neglectful and non-neglectful families, the results
      indicated that children from neglectful families perceived a higher level of
      quality in family functioning that was not reported by caseworkers or supported
      by other measures. CONCLUSIONS: Implications for designing effective
      interventions for school-age and adolescent children from neglectful families are
      discussed.

PMID- 9777257
TI  - Preliminary validation of the Child Abuse Potential Inventory in Chile.
AB  - OBJECTIVE: The objective of this work is a preliminary validation in Chile of the
      Child Abuse Potential (CAP) Inventory (Milner, 1986). METHOD: A sample of 134
      participants was drawn from Santiago's Metropolitan Area and the city of Iquique
      in Chile, divided into two groups: people identified as physical abusers of their
      own children and people identified as nonabusers. As a result of the sampling
      procedure, the study group was composed of 64 women and three men. This
      distribution was matched in the control group. A reliability analysis, a
      predictive and construct validity analysis, and an item analysis of the Abuse
      Scale proposed by Milner were performed. RESULTS: The Abuse Scale items were
      tabulated both with the weighted scores proposed by Milner and with simple
      scores. The results were more consistent with simple scores. It correctly
      classified 90% of respondents (91% in the abuse group and 88% in the control
      group). Of the 76 items of the Abuse Scale, 55 were highly discriminatory, six of
      them were nonsignificant and 15 of them had differences that were not great
      enough so as to discriminate people well. To evaluate the dimensionality of the
      items, a factor analysis was carried out. The best solution (Oblimin rotation)
      was obtained with 6 factors, which accounts for 53.8% of the variance.
      CONCLUSION: Milner's Abuse Scale discriminated between abusing and nonabusing
      individuals, and showed a factor analysis similar to the original one. Some items
      reflected cultural conducts in Chile instead of potential abuse: they are related
      with socially desirable neatness and cleanliness of children and home, specially
      in low-income families.

PMID- 9777258
TI  - [Preliminary validation of the Child Abuse Potential Inventory in Argentina].
AB  - OBJECTIVE: To know the ability of the CAP Inventory (Milner, 1986) to
      discriminate between child physical abusers and nonabusers in Argentina, and to
      know its reliability. To conduct an item analysis in order to know the capability
      of the Abuse Scale items for discrimination between both groups of subjects.
      METHOD: The CAP Inventory was applied to two groups of subjects: 40 child
      physical abusers and 40 nonabusers. Both groups were matched in gender, age,
      educational level, family income, martial status, number of children, and gender
      and age of children. RESULTS: Fifty-four items discriminated (p < .05) between
      both groups of subjects. The reliability coefficient of the Abuse Scale was
      adequate (alpha = .94). Twenty items with the best capability for discrimination
      were selected. More than 97% (97.4%) of subjects were correctly classified (94.4%
      for physical abusers and 100% for nonabusers). The Abuse Scale present similar
      psychometric characteristics than the American and Spanish versions. CONCLUSION:
      This is the first study in Argentina with the objective of CAP adaptation and
      validation. The discriminant and predictive capability of the Abuse Scale are
      promising for Argentina. However, complementary studies with different samples
      are needed in order to obtain reliable data and a preliminary version of the
      Inventory.

PMID- 9777259
TI  - Juvenile male rape victims: is the level of post-traumatic stress related to
      personality and parenting?
AB  - OBJECTIVE: The purpose of this study was to assess the level of post-traumatic
      stress in juvenile male rape victims and to test for its relationships with
      perceived parental rearing and personality dimensions. METHOD: Fifteen subjects
      (mean age of 16 years) were recruited from a correctional camp for juvenile
      criminals in Arkhangelsk, Russia. They were investigated by means of the "Revised
      Impact of Event Scale," the "Child Self-Report Post-Traumatic Stress Reaction
      Index," the "Hospital Anxiety and Depression Scale," the "EMBU" (perceived
      parental rearing) and the "Temperament and Character Inventory" (TCI). RESULTS:
      The level of post-traumatic stress, in most cases moderate to high, correlated
      with the temperament dimensions of harm avoidance and reward dependence. As
      concerns parental rearing, the total level of post-traumatic stress reaction was
      negatively correlated with paternal emotional warmth and positively with paternal
      rejection. CONCLUSIONS: The experience of post-traumatic stress is influenced by
      temperamental characteristics as well as by perceived parental rearing practices.
      Assumingly, these factors also play a role in becoming a rape victim, which
      deserves further investigation.

PMID- 9777253
TI  - Metal ion and guanine nucleotide modulations of agonist interaction in G-protein
      coupled serotonin1A receptors from bovine hippocampus.
AB  - 1. The serotonin type 1A (5-HT1A) receptors are members of a superfamily of seven
      transmembrane domain receptors that couple to GTP-binding regulatory proteins (G
      proteins). We have studied the modulation of agonist binding to 5-HT1A receptors
      from bovine hippocampus by metal ions and guanine nucleotide. 2. Bovine
      hippocampal membranes containing the 5-HT1A receptor were isolated. These
      membranes exhibited high-affinity binding sites for the specific agonist [3H]OH
      DPAT. 3. The agonist binding is inhibited by monovalent cations Na+, K+, and Li+
      in a concentration-dependent manner. Divalent cations such as Ca2+, Mg2+, and
      Mn2+, on the other hand, show more complex behavior and induce enhancement of
      agonist binding up to a certain concentration. The effect of the metal ions on
      agonist binding is strongly modulated in the presence of GTP-gamma-S, a
      nonhydrolyzable analogue of GTP, indicating that these receptors are coupled to G
      proteins. 4. To gain further insight into the mechanisms of agonist binding to
      bovine hippocampal 5-HT1A receptors under these conditions, the binding
      affinities and binding sites have been analyzed by Scatchard analysis of
      saturation binding data. Our results are relevant to ongoing analyses of the
      overall regulation of receptor activity for G-protein-coupled seven transmembrane
      domain receptors.

PMID- 9777260
TI  - Psychological disturbance and child sexual abuse: a follow-up study.
AB  - OBJECTIVE: The aim of this prospective study was to identify risk factors for the
      development of psychological disturbance in sexually abused children, enabling
      recognition of the need for appropriate psychological intervention and provision.
      METHOD: A city-wide study of children aged 16 or under was carried out, with all
      cases of CSA requiring investigation within 12 months included. Data were
      collected on 144 children from police, social services, and pediatricians. Follow
      up was by questionnaire and interview with involved professionals at 4 weeks, 9
      months, and 2 years post investigation. RESULTS: Initially, two-thirds of
      children showed emotional or behavioral indicators of disturbance, commonly sleep
      disturbance, temper tantrums, and depression. Over time, there was a substantial
      increase, with anxiety and depression, suicide attempts, substance abuse, lack of
      interaction with peers and sexualized behavior showing increases over the study's
      duration. Age, gender, abuse, and perpetrator characteristics did not show strong
      effects initially. Children involved in criminal proceedings were at particular
      risk. No improvement was evident over time. CONCLUSIONS: In the absence of clear
      risk factors other than initial disturbance, process models involving cognitive
      factors may be helpful in explaining disturbance, and the need for early
      identification of disturbance and intervention is highlighted.

PMID- 9777261
TI  - Characteristics of intrafamilial and extrafamilial child sexual abuse.
AB  - OBJECTIVE: The precise nature of the differences between intrafamilial and
      extrafamilial child sexual abuse is not clear. The purpose of the present study
      is to provide clarification of these differences. METHOD: Archival data
      containing 1,037 cases of child sexual abuse were obtained from police files in
      two western Canadian cities with populations of about 180,000. Two trained
      research assistants coded and transcribed the data. RESULTS: Results showed: (1)
      earlier onset, longer duration, higher level of intrusion, and greater physical
      and emotional injury for intrafamilial victims; (2) less use of physical/verbal
      force, or enticements, and greater use of instructions "not to tell" by
      intrafamilial offenders; (3) more convictions and longer jail sentences for
      intrafamilial offenders; and (4) no intra-extrafamilial differences in victim sex
      preference. CONCLUSIONS: Boys are younger than girls at the time of first abuse
      in samples of criminal justice and hospital referrals, although only for older
      aged victims, for example, 8 to 17 years. Although statistically significant,
      there is little difference in level of intrusion perpetrated by intrafamilial and
      extrafamilial offenders, both are highly intrusive. Both intrafamilial and
      extrafamilial offenders use physical/verbal force, with older victims:
      extrafamilial offenders more often choose older victims, and therefore more often
      use force. Intrafamilial victims suffer greater physical and emotional injury,
      resulting from greater intrusion not duration of abuse. It's not clear that
      victim sex preferences of intra- and extrafamilial offenders exist.

PMID- 9777263
TI  - Law enforcement officers' approaches to evaluations of child sexual abuse.

PMID- 9777264
TI  - Evolution of treatment strategies in multiple myeloma.

PMID- 9777262
TI  - Shaken baby syndrome: report on four pairs of twins.

PMID- 9777265
TI  - Ethnicity study and non-selective screening for haemoglobinopathies in the
      antenatal population of central Manchester.
AB  - The objective of this study was to determine the frequency of ethnic groups
      within the antenatal population in central Manchester and thereby ensure that the
      haemoglobinopathy service was targeting the correct population and their needs.
      Ethnic data collection records of 6718 patients were analysed over a 7 month
      period. Of these 62.3% stated that they were White, 13.2% Asian, 7.9% Black, 3.8%
      Chinese or 'other ethnic groups' and 12.7% gave no information about their ethnic
      background. A subset of 1144 patients were screened for haemoglobinopathies over
      a 1 month period. The incidence of haemoglobinopathies within the screened
      population was 2.62%, and comprised 0.69% beta thalassaemia trait, 1.22% sickle
      cell trait, 0.43% haemoglobin C trait and 0.26% haemoglobin D trait. The total
      incidence of haemoglobinopathies was highest within the Black population (18.2%),
      followed by the no information group (5.6%), Asian (3.35%) and white (0.26%). The
      high proportion of ethnic minorities and the significant carrier frequency in the
      no information group, support our view that non-selective screening should be
      offered to the antenatal population of central Manchester.

PMID- 9777267
TI  - Clinicopathological features of megaloblastic anaemia in Hong Kong: a study of 84
      Chinese patients.
AB  - Megaloblastic anaemia is uncommon in Hong Kong. Eighty-four consecutive Chinese
      patients with megaloblastic anaemia were studied. There were 48 males and 36
      females, with a median age at presentation of 67 years. Vitamin B12 deficiency
      was found in all cases, with none of the patients showing folate deficiency. The
      frequency of pernicious anaemia in our patients was higher than in other south
      east Asian series but comparable with western ones. When compared with patients
      in the West, our cases showed the following main differences: virtual absence of
      folate deficiency, even in alcoholics; absence of associated gastric
      malignancies; and a high frequency of tuberculosis.

PMID- 9777266
TI  - The effect of EDTA as an anticoagulant on the osmotic fragility of erythrocytes.
AB  - The osmotic fragility test is used to determine the extent of red blood cell
      haemolysis produced by osmotic stress. Since the quality of this test may easily
      be influenced by environmental and technical factors we have determined osmotic
      fragility reference values in our own conditions. The results show significantly
      increased osmotic resistance of erythrocytes in our conditions vs the published
      values for blood samples anticoagulated with heparin. Furthermore, the use of
      EDTA as an anticoagulant increased the osmotic fragility of red blood cells as
      compared with heparin. We conclude that EDTA can be used as an anticoagulant for
      the osmotic fragility test in order to simplify routine procedures. However,
      every laboratory should determine its own reference values which would reflect
      the local environmental and technical factors.

PMID- 9777268
TI  - Detecting residual bcr-abl transcripts in chronic myeloid leukaemia patients
      using coupled reverse transcriptase-polymerase chain reaction with rTth DNA
      polymerase.
AB  - The bcr-abl fusion gene is the hallmark of chronic myeloid leukaemia (CML) and
      presumably the cause of its development. Accordingly, long-term disappearance of
      the bcr-abl gene after intensive therapy suggests that a patient is probably
      cured of CML. The diagnostic protocol based on coupling of two enzymatic
      reactions, reverse transcription (RT) and nested polymerase chain reaction
      (nPCR), for the detection of bcr-abl transcripts in peripheral blood provides a
      powerful tool for minimal residual CML detection. We have developed a new
      detection protocol using rTth DNA polymerase as the only enzyme catalysing both
      reactions for simplifying CML diagnosis. We demonstrate its efficacy
      investigating residual leukaemic cells in the peripheral blood of 10 patients.
      This assay offers several advantages over the use of conventional RT-PCR, being
      more sensitive, faster, less prone to false positives since no opening of the
      tube is required between the two reactions and requires no special oils or waxes.
      Our simple assay for bcr-abl chimeric transcripts detection is a practical
      addition to the diagnostic evaluation of the patient with chronic myeloid
      leukaemia.

PMID- 9777269
TI  - Action of interleukin-3 on the proliferation of leukaemic progenitor cells from
      patients with acute myeloblastic leukaemia.
AB  - In the present study, we examined the effects of interleukin-3 (IL-3) on the
      proliferation of leukaemic progenitor cells from 11 Japanese patients with acute
      myeloblastic leukaemia (AML), including the effect of its combination with
      granulocyte/macrophage colony-stimulating factor (GM-CSF) or granulocyte colony
      stimulating factor (G-CSF). The results showed that IL-3 sufficiently stimulated
      the proliferation of AML progenitor cells in almost all the cases examined, and
      that the stimulation pattern of IL-3 was similar to that of GM-CSF, although
      different from that of G-CSF. Furthermore, IL-3 worked synergistically with G
      CSF, whereas IL-3 and GM-CSF together were less actively synergistic (P < 0.05).
      These findings suggest the possibility of IL-3/G-CSF/cytosine arabinoside (Ara-C)
      combination therapy, which may be able to enhance the cytotoxic effect of Ara-C
      on AML progenitor cells powerfully in a wider range of patients including cases
      refractory for IL-3/Ara-C combination therapy.

PMID- 9777270
TI  - Tumour necrosis factor alpha (TNF alpha) and leukaemic cells: secretion and
      response.
AB  - Leukaemic cells from various types (ALL-O, ALL-proB, ALL-common [cALL], ALL-T) of
      acute lymphoblastic leukaemia (ALL) and non-lymphoblastic leukaemia (ANLL) were
      studied for their ability to produce tumour necrosis factor alpha (TNF). The role
      of exogenous and endogenous TNF in proliferation in vitro of leukaemic cells was
      also assessed. Leukaemic cells from different types of acute leukaemia were found
      to show major differences in their ability to proliferate in vitro. High
      production of TNF was observed mainly in ALL-T and ANLL but in ALL-T it was not
      associated with the proliferation rate of leukaemic cells. In most instances no
      bioactive TNF was detected. The variable response of leukaemic cells (inhibition
      or stimulation of proliferation) to exogenous human recombinant (rTNF) was
      assessed. The role of endogenous TNF as a growth factor or agent associated with
      resistance to exogenous TNF was excluded as judged by a lack of effect of the TNF
      synthesis inhibitor pentoxifylline (PTX) and of anti-TNF antibody and PTX/rTNF.
      There was no association of the effect of rTNF on proliferation of leukaemic
      cells with their immunophenotype, spontaneous release of TNF or proliferation
      rate. Hence, this study does not provide evidence for the role of TNF as a growth
      factor for leukaemic cells or for its role in the inhibition of proliferation of
      leukaemic cells.

PMID- 9777271
TI  - Carnosine and anserine as modulators of neutrophil function.
AB  - Carnosine and anserine, the bioactive peptides found in most meats and fish, were
      tested for their ability to modulate neutrophil and U937 cell function,
      specifically with respect to respiratory burst, interleukin-1 beta production and
      apoptosis. Both peptides increased the respiratory burst and interleukin-1 beta
      production of human neutrophils but not of U937 cells. They suppressed apoptosis
      of human neutrophils but enhanced apoptosis of U937 cells as assessed by DNA
      strand breaks. These results suggest that carnosine and anserine have the
      capacity to modulate the immune response at least in human neutrophils.

PMID- 9777272
TI  - Evaluation of protein C and protein S levels during oral anticoagulant therapy.
AB  - A number of workers have examined protein C in relation to other vitamin K
      dependent factors during warfarin therapy and successfully identified protein C
      deficient patients by ratio calculation. However, protein S deficiency has not
      been addressed in this manner. This study compares protein C and protein S by
      functional and antigenic determination with procoagulant factors of similar half
      life (Factors VII and II) in an attempt to identify protein C and protein S
      deficient patients whilst on oral anticoagulant therapy. Procoagulant and
      anticoagulant factors were compared by linear regression in a population of
      normal blood donors and patients on stabilized warfarin therapy to obtain
      expected values for protein C and protein S dependent upon FVII and FII levels,
      respectively. Observed over expected values for protein C and protein S were
      calculated for individual patients and normal ranges derived. Comparison of
      similarly calculated observed over expected protein C and protein S ratios with
      these normal ranges successfully identified known protein C and protein S
      deficient patients who were taking warfarin at time of testing.

PMID- 9777274
TI  - Delayed diagnosis and unnecessary percutaneous biopsies in cases of myeloma
      presenting as chest wall tumours.
AB  - We report on five cases of myeloma presenting at a single institution over an 8
      year period between 1988 and 1996. All presented with bony pain and a chest wall
      mass arising from a rib on chest X-ray. Myeloma was not confirmed until 22, 25
      and 50 days after admission in three of the cases who each suffered a potentially
      hazardous percutaneous chest wall biopsy which was undiagnostic. A fourth case
      did not suffer diagnostic delay as his biopsy showed sheets of plasma cells
      although, as in all five cases, evidence of myeloma was clearly present on
      serum/urine electrophoresis, skeletal survey and marrow aspirate, making chest
      wall biopsy unnecessary. The only case who suffered no diagnostic delay and no
      percutaneous chest wall biopsy was the only case to have a comprehensive chest X
      ray report listing myeloma as a differential diagnosis and suggesting a
      haematology referral.

PMID- 9777273
TI  - Audit of patients on oral anticoagulants with International normalized ratios of
      eight or above.
AB  - We reviewed retrospectively the medical records of all patients (n = 77, mean age
      74.2) on oral anticoagulants with an International normalized ratio (INR) of
      eight or above in a 12-month period in the Leicestershire District Health
      Authority (DHA). From a total of 55,625 INRs, 131 (0.24%) were > or = 8. A major
      cause of over-anticoagulation was unsatisfactory dose loading during in-hospital
      commencement of oral anticoagulation. The incidence of major bleeding was 12.9%
      of total episodes of INR > or = 8 with two haemorrhage-related fatalities.
      Therapy of major haemorrhage with fresh frozen plasma (FFP) and intravenous (i.v)
      vitamin K proved effective but was not given in a majority of such cases. In
      conclusion, improvements in initial dose loading of oral anticoagulation and in
      the management of major haemorrhage are required. Severely over-anticoagulated
      patients without obvious bleeding should nevertheless receive small dose vitamin
      K therapy to reduce the risk of haemorrhage related morbidity and mortality
      without compromising subsequent oral anti-coagulant control.

PMID- 9777275
TI  - Insight and illness in chronic schizophrenia.
AB  - The role of insight in relation to the diagnosis and treatment of psychotic
      disorders has received renewed attention in psychiatric and psychological
      literature. Degree of insight has been found to generally associate with social
      and occupational functioning, prognosis, and treatment outcome. However, the
      relationship between insight and symptoms of illness is not known due to previous
      studies that yielded conflicting results. This study tested the association
      between general insight and symptomatology in a sample of 66 patients with
      chronic schizophrenia. Degree of insight was significantly related to positive
      symptomatology; however, it was not related to demographics, negative symptoms,
      general psychopathology, or global functioning. These results are supported by
      several other investigations in this area.

PMID- 9777276
TI  - Insight in paranoid schizophrenia--its relationship to psychopathology and
      premorbid adjustment.
AB  - The patient's insight in the course of a mental disease has recently become a
      matter of interest for psychiatrists. Various aspects of insight are examined, as
      well as the relationship between insight and different clinical variables. In the
      current study, we examined correlations between aspects of insight and intensity
      of psychopathological symptoms, occurrence of the various types of delusions, and
      the level of premorbid adjustment in patients with paranoid schizophrenia. We
      found significant relationships between poor insight and negative symptoms,
      thought-broadcasting, delusions of grandeur and sexual delusions, and worse
      premorbid adjustment in late adolescence and adulthood.

PMID- 9777277
TI  - Specificity of eating disorders diagnoses in families of probands with anorexia
      nervosa and bulimia nervosa.
AB  - This study examines the prevalence of anorexia nervosa and bulimia nervosa in
      relatives of probands, and examines the probandwise specificity of any familial
      clustering. Data were collected from probands using the family history method.
      Probands were recruited in a sequential cohort fashion. Information collected
      from probands was rated semiblindly by two of the authors, and a diagnostic
      hierarchy applied to arrive at a diagnosis for each of the relatives assessed.
      Data are reported on 2,125 family members, collected from 93 probands. Diagnostic
      agreement between raters was high, with serious disagreement present in three of
      167 possible cases of an eating disorder. Rates of anorexia nervosa, bulimia
      nervosa, major depression, and substance abuse declined from first- to third
      degree relatives, which is consistent with genetic clustering, and there was
      evidence of a cohort effect operating for anorexia nervosa and bulimia nervosa.
      The rates of anorexia nervosa and bulimia nervosa in all family members were
      5.1%, and 4.3% respectively. An analysis of maternal and paternal descent showed
      no evidence for X-linked dominant transmission in these families. Preliminary
      analysis of the clustering of diagnoses in relatives showed a tendency (chi 2 =
      14.47, P = .006) for family members to be affected by the same diagnosis as was
      the proband. This trend was strongest for anorexia nervosa, but there was overlap
      when the proband had a lifetime diagnosis of bulimia nervosa, with or without
      anorexia nervosa. These results are compatible with the existence of genetic
      factors influencing predisposition to eating disorders, but do not prove such.

PMID- 9777278
TI  - Body dysmorphic disorder in psychiatric outpatients: recognition, prevalence,
      comorbidity, demographic, and clinical correlates.
AB  - The prevalence of Body Dysmorphic Disorder (BDD), based on structured and
      unstructured clinical interviews, was compared in two samples of psychiatric
      outpatients drawn from the same practice setting. In the first sample, 500
      patients were diagnosed according to a routine, unstructured clinical interview.
      In the second sample, 500 subjects were diagnosed according to information
      obtained by the Structured Clinical Interview for DSM-IV (SCID). No patient was
      diagnosed with BDD in the clinical sample, whereas 16 (3.2%) patients were
      diagnosed with BDD in the SCID sample. Compared with patients without BDD,
      patients with BDD received significantly more current axis I diagnoses, and were
      more likely to be diagnosed with current obsessive-compulsive disorder (OCD) and
      social phobia. Both groups were diagnosed with major depression at similar rates.
      Patients with BDD, versus those without, tended to be sicker and more
      functionally impaired. It appears that BDD is an infrequent disorder in an
      outpatient setting, which is rarely recognized when clinicians conduct their
      routine diagnostic interview. Although it was not usually a patient's principal
      reason for seeking treatment, the majority of patients with BDD in this sample
      wanted their treatment to address these symptoms.

PMID- 9777279
TI  - Dissociative symptomatology and aggressive behavior.
AB  - The present study examined the relationship between dissociative symptomatology
      and a range of aggressive behavior in a general psychiatric outpatient
      population. Of the total sample (n = 122), 29% scored above 25 on the
      Dissociative Experiences Scale (DES). Patients with high DES scores (> 25) were
      significantly more likely than patients with lower DES scores (< 25) to report a
      history of childhood sexual abuse, to have attempted suicide, and to report more
      assaultive behavior, irritability, and negativism. There were no differences
      between the patients with high versus low DES scores on homicidal behavior. To
      better manage and treat outpatients with dissociative symptomatology, it is
      important to clarify the association between outwardly aggressive behavior and
      dissociative experiences.

PMID- 9777280
TI  - Identifying the unique and common characteristics among the DSM-IV antisocial,
      borderline, and narcissistic personality disorders.
AB  - A clinical chart-review study of the Cluster B personality disorders (PDs) was
      conducted to evaluate the specificity of DSM-IV criteria for the Antisocial
      Personality Disorder (ANPD), Borderline Personality Disorder (BPD), and
      Narcissistic Personality Disorder (NPD). Eight-six outpatients meeting DSM-IV
      criteria for a PD were identified through a retrospective chart-review procedure.
      Records of these 86 patients were independently rated on all of the ANPD, BPD,
      and NPD symptom criterion for the DSM-IV. High interrater reliabilities were
      obtained for the presence or absence of a PD and symptom criteria for ANPD, BPD,
      and NPD (all kappa > or = .80). The sample consisted of ANPD (n = 20), BPD (n =
      25), NPD (n = 15), and other personality disorders (OPD; Cluster A and C; n =
      26). Five ANPD criteria reliably differentiated ANPD patients from BPD and NPD
      patients (1, 2, 3, 6, 7), and two criteria did not differentiate this group from
      either intracluster category (4, 5). BPD criteria also differentiated BPD
      patients from ANPD and NPD patients; however, the specific criteria that
      effectively differentiated categories were dependent on the group comparisons.
      BPD criteria (1, 2, 3, 6, 7) differentiated BPD and ANPD patients. BPD and NPD
      patients could be discriminated on other BPD criteria (2, 3, 5, 6, 7, 8). NPD
      criteria showed a similar ability to differentiate patients. NPD criteria
      differentiated NPD and BPD patients on DSM-IV criteria of 1, 3, 4, 5, 7, and 9.
      NPD and ANPD patients could be differentiated on other NPD criteria (1, 2, 3, 4,
      5, 9). The results of this study provide general support for the use of specific
      criteria for these three disorders in the differential comparison of related and
      unrelated PDs. The utility of items that describe essential features are
      discussed.

PMID- 9777281
TI  - Symptoms of prototypic patients with passive-aggressive personality disorder: DSM
      IIIR versus DSM-IV negativistic.
AB  - This study examined features of patients that clinicians identified as good
      examples of Passive-Aggressive Personality Disorder to identify core features of
      the disorder and to determine which set of criteria (DSM-III-R, two definitions
      in the DSM-IV Options Book, or DSM-IV Negativistic) best characterized the
      identified patients. A national sample of licensed psychologists (N = 68)
      identified a patient who (based on symptoms) was a good example of Passive
      Aggressive Personality Disorder. They then rated the patient on a symptom
      checklist composed of the Passive-Aggressive and Negativistic criteria, as well
      as other personality-disorder symptoms that overlap with Passive-Aggressive.
      Clinicians identified patients they considered exemplars for Passive-Aggressive
      Personality Disorder, and there was moderate consensus about their characteristic
      symptoms. DSM-III-R symptoms received the highest ratings, and there was little
      overlap with other personality disorders. Principal-component factor analysis
      suggested that a general pattern of passive resistance, along with a behavioral
      manifestation of procrastination and a second group of symptoms suggesting
      interpersonal difficulties, were the features of these passive-aggressive
      patients. More male patients were identified as good examples of the disorder,
      and female patients presented a more heterogeneous diagnostic picture.
      Implications and directions for future research are discussed, including the need
      to integrate research findings from the differing perspectives on personality
      disorders.

PMID- 9777282
TI  - Axis II comorbidity of borderline personality disorder.
AB  - The purpose of this study was to assess the prevalence of a full range of DSM-III
      R axis II disorders in a sample of criteria-defined borderline patients and axis
      II controls. The axis II comorbidity of 504 personality-disordered inpatients was
      assessed blind to clinical diagnosis using a semistructured research interview.
      Odd, anxious, and dramatic cluster disorders were each common among borderline
      patients. However, only odd and anxious cluster disorders were significantly more
      common among borderline patients (N = 379) than axis II controls (N = 125).
      Paranoid, avoidant, and dependent personality disorders were the most highly
      discriminating disorders between borderline patients and controls. In addition,
      male and female borderline patients exhibited somewhat different patterns of
      comorbidity. Although the rates of avoidant and dependent personality disorders
      were similar, male borderlines were significantly more likely than female
      borderlines to meet DSM-III-R criteria for paranoid, passive-aggressive,
      narcissistic, sadistic, and antisocial personality disorders. These results
      suggest that there is a particularly strong relationship between anxious cluster
      disorders and borderline personality disorder (BPD). They also suggest that
      gender plays an important role in the expression of axis II comorbidity,
      particularly with respect to dramatic cluster disorders.

PMID- 9777283
TI  - The differential effect of personality on computer-based treatment of
      agoraphobia.
AB  - The differential effects of the revised NEO Personality Inventory (NEO PI-R)
      personality factors and intelligence on response to a computerized vicarious
      exposure treatment for agoraphobia were investigated. The Fear Questionnaire
      (FQ), the Agoraphobia Cognitions Questionnaire (ACQ), and the Body Sensations
      Questionnaire (BSQ) were used to assess agoraphobic symptomatology. Fourteen
      females and four males with agoraphobia diagnoses completed three 45-minute
      weekly treatment sessions. There was a significant decrease in scores on all
      three measures following treatment. Compared with published population norms, the
      agoraphobic subjects showed very high neuroticism, low extroversion, and high
      openness. Lower agreeableness factor scores predicted good treatment outcome. The
      NEO PI-R openness factor was negatively correlated with proficiency on the
      computer program; however, proficiency on the computer program did not correlate
      with symptom improvement. Overall, these results suggest that personality
      interacts with treatment at different stages of the therapeutic process.

PMID- 9777284
TI  - Obsessive-compulsive disorder among schizophrenic patients: an exploratory study
      using functional magnetic resonance imaging data.
AB  - Despite the growing research on the etiology of obsessive-compulsive disorder
      (OCD), and schizophrenia, the clinical distinction between the two disorders is
      not clearly understood. In the present investigation, we sought to better
      understand the relationship between OCD and psychotic disorders by examining
      functional magnetic resonance imaging (fMRI) data from a group of schizophrenic
      patients with varying degrees of OCD symptomatology, based on results of the Yale
      Brown Obsessive Compulsive Scale (Y-BOCS) and the National Institute of Mental
      Health (NIMH) rating scales of OCD. While subjects performed a cognitive
      challenge paradigm that included a verbal fluency task, activation data from the
      left dorsolateral prefrontal cortex were collected and analyzed. We hypothesized
      that the fMRI signal patterns in schizophrenic patients with high levels of OCD
      symptomatology would differ from that of schizophrenic patients with a low level
      of OCD. For the group as a whole, no significant relationship was found for
      scores of either rating scale and fMRI signal change; however, a significant
      association was found for a subgroup of patients. For these schizophrenics, there
      was a negative relationship between OCD symptomatology and activation of the left
      dorsolateral prefrontal cortex. These results support the suggestion of several
      researchers that a relationship between OCD severity and neurophysiological
      activity exists in schizophrenia.

PMID- 9777285
TI  - The perception of sleep as a function of the level of daytime sleepiness among
      patients with obstructive sleep apnea.
AB  - Subjective estimates of sleep onset among patients with a variety of sleep
      disorders have been shown to be inaccurate. This inability in perceiving sleep
      onset is potentially dangerous for this population, in particular, for
      individuals who are required to drive long distances or operate heavy machinery
      as part of their daily activities. This study evaluated the perception of sleep
      among 237 consecutive patients diagnosed with obstructive sleep apnea. Patients
      completed an overnight sleep-laboratory evaluation followed by an objective
      evaluation of sleep propensity. The latter was done using the Multiple Sleep
      Latency Test (MSLT). Patients with an accurate perception of having slept on the
      MSLT were found to have shorter sleep latencies when compared with those with an
      inaccurate perception of their sleep. The results of this study suggest that the
      rapidity with which sleep is manifested is an important contributor to the
      accurate perception of sleep.

PMID- 9777286
TI  - Autoenucleation--a culture-specific phenomenon: a case series and review.
AB  - Cases of autoenucleation may provide a good example of the pathoplastic effects
      of culture. To further characterize this phenomenon, the author reviewed the
      medical literature and conducted a retrospective search of the local psychiatric
      hospital records. Medline search did not show a single case of autoenucleation in
      the non-European Christian culture. Descriptive accounts of the identified seven
      patients show they were all psychotic at the time of the act, and five had a
      history of prior drug abuse. Most were religiously preoccupied before the act and
      displayed prominent affective symptoms, and they all interpreted the Biblical
      text literally. The association of sight and the concept of sin is discussed in a
      wider cultural context, and it is proposed that autoenucleation may be unique to
      the Christian West.

PMID- 9777287
TI  - The feed-back regulation of erythropoietin production in healthy humans.
AB  - The proposed oxygen-dependent feed-back loop regulation of EPO production (Fogh
      1978, Erslev 1991, LeHir et al 1991, Nielsen 1991) is mainly supported by data
      from studies in animals and cell cultures. The feed-back loop and its dependence
      on oxygen was therefore challenged by studies in healthy humans: Exposure of
      humans to different levels of acute and continued altitude hypobaria provided
      evidence for an oxygen dependency of the EPO response. This response is
      consistent with the proposed feed-back loop regulation of EPO production.
      Exposure to continued altitude hypobaria demonstrated that the decline in human
      EPO production is initiated before an EPO-induced erythropoiesis is detectable,
      and that this decline is related to a concomitant decrease in the haemoglobin
      oxygen affinity. Contrary to the feed-back loop, this time-relation indicate that
      the feed-back regulation of EPO production during continued hypobaric hypoxia is
      exerted primarily through a decrease in the haemoglobin-oxygen affinity, rather
      than by the effects of an EPO-stimulated erythropoiesis. A laboratory experiment
      demonstrated that the lowering of PaO2 by short-term breathing of hypoxic gas
      could trigger human EPO production. Since the possible influence of spontaneous
      non-hypoxic variations in EPO production was taken into account, the magnitude of
      the human EPO response to hypoxia was found to be less than formerly observed in
      humans and rodents. Contrary to former observations in rodents, the triggering of
      human EPO production was not related to a hypoxic or normoxic increase of the
      haemoglobin-oxygen affinity, and normocapnia, without changes in pH or
      haemoglobin-oxygen affinity, sufficed to suppress the human EPO response to
      hypoxia. Together with the altitude studies, these results have demonstrated that
      human EPO production is dependent on, and triggered by, oxygen deprivation, and
      that changes in the haemoglobin-oxygen affinity play a role mainly in the feed
      back regulation rather than in the triggering of human EPO production. Increased
      circulating levels of the proinflammatory cytokine IL-6 was found in healthy
      humans during four days of altitude exposure as compared with sea level. The
      other proinflammatory cytokines IL-1 beta, and TNF alpha remained unchanged, and
      the increased serum IL-6 did not induce production of c-reactive protein.
      However, a relation was shown between serum IL-6, SaO2, and serum EPO. These
      observations in humans confirm earlier in vitro studies in that IL-6 may have a
      co-stimulatory role on EPO production in the presence of hypoxia. Comparable
      circadian variations in human EPO production were shown in sedentary subjects,
      athletes, and healthy but hypoxaemic subjects. Human EPO production could not be
      triggered by one hour of high-intensity exercise, whereas longitudinal changes in
      exercise showed a trend of relation between human EPO production, serum
      concentration of free testosterone, and indices of body composition. These
      results have demonstrated an endogenous, probably hormonal, and oxygen
      independent regulation of human EPO production, which is at variance with the
      oxygen dependent feed-back loop regulation of EPO production. Conclusively, the
      present investigations have shown that the feed-back loop regulation of EPO
      production, as described by studies in rodents and cell-culture models, cannot be
      applied to the physiology of human EPO production without modifications.

PMID- 9777288
TI  - Promotion, prediction, and prevention of progression in diabetic nephropathy.

PMID- 9777289
TI  - Familial defective apolipoprotein B-100.
AB  - Abnormal interaction between low density lipoprotein receptors (LDLR) and their
      ligands, apolipoprotein E and B, causes decreased catabolism of lipoproteins
      which carry these apolipoproteins (VLDL, IDL and/or LDL) and thereby increased
      plasma concentrations of these. In familial hypercholesterolemia (FH), abnormal
      interaction is due to mutations in the LDLR gene, and in type III hyperlipidemia
      due to mutations in the apo E gene. A few mutations in the apolipoprotein B (apo
      B) gene have been described, of which the apo B-3,500Arg-Gln seems by far the
      most frequent, that causes defective binding to normal LDLR. The metabolic
      disorder associated with these mutations has been named familial defective
      apolipoprotein B-100 (FDB). The frequency of the apo B-3,500Arg-Gln mutation is
      particularly high in Central Europe (Switzerland) with lower frequencies south of
      the Alpes, in Russia and in Scandinavia. We found an incidence of 1/1250 of the
      mutation in Denmark (III), employing a DNA based assay optimized to allow
      detection of the mutation in very small amounts of DNA (I). Since other mutations
      in the receptor binding domain of the apo B-100 have been described, we developed
      another DNA based assay, employing DGGE technique, to screen for other mutations
      in the region of amino acid 3,456 to 3,553 (II). However, no other mutations but
      the apo B-3,500Arg-Gln have so far been detected in Danish hypercholesterolemic
      patients. In a study of 5 Danish families with FDB (46 heterozygous FDB patients
      and 57 unaffected relatives) we found that FDB patients had significantly
      increased mean cholesterol and LDL cholesterol concentrations, but with a wide
      range of variation and with approximately 30% having cholesterol concentrations
      below the 95th percentile for the general population (IV). This was confirmed in
      a compilation of data on 205 FDB patients from the Netherlands, Germany and
      Denmark (V). In this study we also compared the biochemical and clinical features
      of FDB with those of 101 Danish FH patients in whome FDB had been ruled out. Our
      data support, that the LDL cholesterol elevation is less pronounced in FDB than
      in FH and that the age-specific prevalence of atherosclerotic cardiovascular
      disease (CVD) is lower in FDB than in FH. In the compiled study of 205 FDB
      heterozygotes (V), we found that age, gender and genetic variation in the LDLR
      gene explained a considerable part of the between-individual variation in total
      and LDL cholesterol. We conducted a prospective study of the lipid lowering
      effect of pravastatin and gemfibrozil in 30 Danish FDB patients (VI). Together
      with other, retrospective, studies, we conclude that the cholesterol lowering
      effect of HMG-coA-reductase inhibitors, anion binding resins and nicotinic acid
      is fully comparable to that observed when treating FH patients and type IIa
      hypercholesterolemic patients, without clinical signs of FH.

PMID- 9777290
TI  - Measurement of histamine release in intact human skin by microdialysis technique.
      Clinical and experimental findings.

PMID- 9777291
TI  - Transabdominal chorionic villus sampling. Method, safety and accuracy.

PMID- 9777292
TI  - Chemotherapy-induced nausea and vomiting with special emphasis on metopimazine.

PMID- 9777293
TI  - Co-contraction of antagonistic muscles in man.

PMID- 9777294
TI  - Prevalence of hypercalcaemia in normal and in hospital populations.
AB  - The purpose of the present study was to review the literature with respect to the
      prevalence of hypercalcaemia in normal and in hospital populations. Pertinent
      studies were selected from the MEDLINE database (1980 to March 1995) and through
      the bibliographies of selected articles. Hypercalcaemia is one of the most common
      metabolic disorders in malignant diseases and develops in 3-30% of such patients.
      Hypercalcaemia of malignancy is the most common cause of hypercalcaemia followed
      by primary hyperparathyroidism in hospital populations. The most common cause in
      normal populations is primary hyperparathyroidism followed by transient
      hypercalcaemia. The prevalence of hypercalcaemia shows a large variation in
      hospital populations ranging from 0.17% to 2.92%. The prevalence in normal
      populations varies between 1.07% and 3.9% and, surprisingly exceeds the level in
      hospital populations. The discrepancies between prevalences may be due to varying
      referral patterns, different distribution of specialities causing different
      hospital populations and different definitions of hypercalcaemia. Hypercalcaemia
      presents a diagnostic problem. The percentage of cases of hypercalcaemia that are
      actually diagnosed has been observed to be as low as 25% in hospitals, in which
      laboratory results remain unreported unless requested. But even when presented,
      20-50% of the cases are overlooked.

PMID- 9777295
TI  - Outpatients' knowledge about and attitude towards clinical research and
      randomized clinical trials. The INFO Trial Group.
AB  - OBJECTIVES: To investigate the knowledge about randomized clinical trials and the
      attitude towards clinical research among Danish outpatients and to examine the
      relationships between outpatient demographic variables and knowledge and
      attitude. SETTING: Outpatients (n = 415) were recruited from four departments at
      a university hospital in Copenhagen. METHODS: The participants answered an 18
      item multiple choice test evaluating knowledge about randomized clinical trials
      and a 32 item Likert format questionnaire evaluating attitudes towards clinical
      research in general and randomized clinical trials. Assessment of scales for
      knowledge and attitudes was performed using Rasch analysis and Cronbach's alpha.
      Associations between demographic variables, knowledge score and attitude score
      were examined using analysis of variance. RESULTS: Mean age for all outpatients
      was 46 years (range 18-88 years); 251 (60%) were females. A total of 27
      outpatients (7%) had previously participated in a randomized clinical trial. Mean
      knowledge score (number of correct answers out of a maximum of 17) was 7.9 (SD
      3.1). Patients in the younger age groups and patients with longer education had
      significantly higher knowledge scores (p < 0.001). The effect of age group
      (estimated increase in knowledge score relative to the group 60-89 years) was: 18
      29 years 1.2 (SE 0.4); 30-39 years 2.0 (SE 0.4); and 40-59 years 1.6 (SE 0.4).
      The effect of education (estimated decrease in knowledge score relative to
      patients with > 12 years of education) was: < 7 years 3.4 (SE 0.4); and 8-11
      years 2.0 (SE 0.3). Mean total attitude score was 74.8 (SD 14.8) on a scale from
      0-128. Compared to female patients, male patients had an estimated 5.1 points (SE
      1.5) higher attitude score (p < 0.001). There was a weak but significant positive
      association (r = 0.38; p < 0.001) between the knowledge score and the total
      attitude score. CONCLUSION: Among Danish outpatients knowledge about randomized
      clinical trials is better in the younger age groups and in individuals with
      longer education. Overall, better knowledge was associated with a more positive
      attitude towards clinical research. The question is whether it is possible by
      simple means to increase knowledge about clinical research and whether an
      increase in knowledge may positively affect the attitude towards clinical
      research in individual patients.

PMID- 9777296
TI  - [Calcium-independent induction of thyroid gland calpains].

PMID- 9777297
TI  - [Distribution of birds and mammals in the Pechora and Kara Seas in the spring of
      1997].

PMID- 9777298
TI  - [Development of the vestibular apparatus of the lesser rorqual in comparison to
      development of auditory structures (Cetacea: Mysticeti- Balaenoptera
      acutorostrata)].

PMID- 9777299
TI  - [Unfolding of the tRNA(Phe) structure by complementary oligonucleotides].

PMID- 9777300
TI  - [Effect of 5,6-dihydroxytryptamine on membrane and threshold potentials of
      command neurons during long-term sensitization in the Helix snail].

PMID- 9777301
TI  - [Effect of the dietary vitamin concentrate Ammivit on survival of irradiated
      BALB/c mice].

PMID- 9777302
TI  - [Disturbances in the Drosophila stress reaction correlate with changes in the
      heat-shock response].

PMID- 9777305
TI  - [On the validity of the elephant genus Archidiscodon].

PMID- 9777303
TI  - [Antiviral activity of fullerene (60)C complexed with poly(N-vinylpyrrolidone)].

PMID- 9777304
TI  - [Participation of specific cell surface proteins in the transport of nucleic
      acids into cells].

PMID- 9777306
TI  - [Some reactions of the adaptation mechanism in animal and plant cells upon
      exposure to stress].

PMID- 9777307
TI  - [Histogenesis of perineal gland cells from the pangolin (Manis javanica Demarest,
      1821, Pholidota, Mammalia) during organ culture in diffusion chambers].

PMID- 9777308
TI  - The future role of anti-tumour necrosis factor-alpha products in the treatment of
      Crohn's disease.
AB  - Tumour necrosis factor-alpha (TNF alpha) is thought to play a central role in the
      immunopathology of Crohn's disease, particularly since its levels are raised in
      all types of cells, tissues and secretory fluids of these patients and in animal
      models of the disease. In addition, TNF alpha has been found to modulate a number
      of different processes within the network of inflammatory reactions and therefore
      has become a target molecule for intervention studies. In the past few years
      several compounds have been developed which neutralise or impair the production
      of TNF alpha, e.g. monoclonal antibodies [infliximab (cA2), CDP-571], TNF
      receptor p75-Fc fusion protein, pentoxifylline (oxpentifylline), p65 antisense
      oligonucleotides and metalloproteinase inhibitors, thereby counteracting the
      deleterious effects of this proinflammatory cytokine. At present, successful
      treatment of active 'refractory' and fistulising Crohn's disease has been
      reported with anti-TNF alpha antibodies; more clinical studies are in progress or
      will be performed with substances that intervene in the activation, production
      and processing of TNF alpha. Although important aspects of this type of immune
      intervention therapy still need to be elucidated, e.g. long term effects,
      mechanism(s) of action, identification of responders and nonresponders, etc., it
      is obvious that the integration of basic and clinical research brings us to a new
      era of specific cytokine-directed therapy in Crohn's disease.

PMID- 9777310
TI  - Disease-modifying antirheumatic drugs. Using their clinical pharmacological
      effects as a guide to their selection.
AB  - Rheumatoid arthritis is a disease of unknown aetiology characterised by
      persistent joint swelling, functional disability and increased mortality. No
      curative therapy exists at present but some therapeutic agents, commonly referred
      to as disease-modifying drugs, offer the potential for suppression of the
      inflammatory activity and attenuation of the disease process. Since the precise
      mechanism of action of most disease modifying drugs is uncertain, the selection
      of a particular therapy must at present be based on the pharmacologic properties
      of each available agent, appropriately individualised for each clinical setting.
      The toxicity of disease-modifying agents often limits the dose and/or duration of
      therapy and makes careful monitoring mandatory. No consensus exists as to the
      order in which disease-modifying agents should be employed. Less toxic disease
      modifying drugs such as auranofin, hydroxychloroquine, minocycline, and
      sulfasalazine are usually used in early and mild disease. Azathioprine,
      penicillamine (D-penicillamine), methotrexate and parenteral gold are usually
      considered to be more toxic and are most often used in the setting of progressive
      disease while the most toxic agents, such as chlorambucil and cyclophosphamide,
      are reserved for life-threatening manifestations such as vasculitis. Newer
      therapeutic approaches presently under study include the use of existing drugs in
      combination and novel biologic agents which selectively inhibit lymphocyte and
      cytokine activity. These strategies offer the hope of more efficacious and less
      toxic therapy in the future.

PMID- 9777311
TI  - Rational drug therapy recommendations for the treatment of patients with
      Sjogren's syndrome.
AB  - The aetiology of Sjogren's syndrome (SS) is unknown, and consequently curative
      treatments are not available. The immunopathogenesis of SS is partly clarified
      and immune-regulating drugs (IR) may therefore be of therapeutic value. However,
      the present understanding of SS is still too unclear to allow an exact and
      evidence-based algorithm for therapeutic decision making. Rational drug
      recommendations for the therapy of SS must, therefore, rely mostly on empirical
      data. Several IR drugs have been shown to be able to downregulate the
      immunopathological activity of primary SS, but it is not certain whether the
      diagnostic and cardinal manifestations from the eyes and mouth can be improved.
      In primary SS the disease-modifying qualities of IR and cytotoxic drugs,
      therefore, largely apply to the treatment of severe internal organ involvement,
      inflammatory vascular disease and malignant B lymphocyte disease. In secondary SS
      the IR therapy is directed against the basic immunoinflammatory connective tissue
      disease. Symptom-modifying therapies include drugs to stimulate and substitute
      for exocrine functions, and drugs to treat complications of the exocrine disease
      manifestations and to improve the various nonexocrine disease manifestations. The
      main drugs available for increasing lacrimal and salivary gland output are
      bromhexine and pilocarpine, respectively. However, exocrine substitutes, and in
      particular eye drops, are still the most important means of alleviating the sicca
      symptoms. They are also indispensable local treatment measures which may help to
      prevent mucosal complications.

PMID- 9777312
TI  - Levobupivacaine.
AB  - Levobupivacaine is an enantiomer of the long-acting local anaesthetic
      bupivacaine, which, although currently the most widely used agent in surgery and
      obstetrics, is associated with potentially fatal cardiotoxicity. Levobupivacaine
      75 to 122 mg was less arrhythmogenic than the same dose range of bupivacaine in
      healthy volunteers. Its effects on the corrected QT interval were significantly
      weaker than those of bupivacaine, and it tended to have a weaker effect on QRS
      duration. The CNS depressant effect of intravenous levobupivacaine 40 mg was less
      than that of bupivacaine 40 mg in healthy volunteers, both in terms of the
      magnitude of the effect and the regions of the cortex affected. Clinical studies
      have demonstrated that epidural levobupivacaine produces a sensory and motor
      block clinically similar to that of bupivacaine in patients requiring anaesthesia
      during surgery. However, the duration of sensory block was significantly longer
      with levobupivacaine 0.75% than with levobupivacaine 0.5% or bupivacaine 0.5% or
      0.75% in one study. Levobupivacaine 0.25% was as effective as bupivacaine 0.25%
      in women requiring epidural anaesthesia during labour with respect to time to
      onset of pain relief, overall quality of analgesia, extent of sensory blockade
      and number of patients reporting motor block. Levobupivacaine is as well
      tolerated as bupivacaine. In a clinical study involving 88 patients who received
      either drug, intraoperative hypotension was the most commonly reported adverse
      event with levobupivacaine and no serious arrhythmias occurred.

PMID- 9777309
TI  - Proton pump inhibitors. Pharmacology and rationale for use in gastrointestinal
      disorders.
AB  - Proton pump inhibitors (PPIs) are drugs which irreversibly inhibit proton pump
      (H+/K+ ATPase) function and are the most potent gastric acid-suppressing agents
      in clinical use. There is now a substantial body of evidence showing improved
      efficacy of PPIs over the histamine H2 receptor antagonists and other drugs in
      acid-related disorders. Omeprazole 20 mg/day, lansoprazole 30 mg/day,
      pantoprazole 40 mg/day or rabeprazole 20 mg/day for 2 to 4 weeks are more
      effective than standard doses of H2-receptor antagonists in healing duodenal and
      gastric ulcers. Patients with gastric ulcers should receive standard doses of
      PPIs as for duodenal ulcers but for a longer time period (4 to 8 weeks). There is
      no conclusive evidence to support the use of a particular PPI over another for
      either duodenal or gastric ulcer healing. For Helicobacter pylori-positive
      duodenal ulceration, a combination of a PPI and 2 antibacterials will eradicate
      H. pylori in over 90% of cases and significantly reduce ulcer recurrence.
      Patients with H. pylori-positive gastric ulcers should be managed similarly. PPIs
      also have efficacy advantages over ranitidine and misoprostol and are better
      tolerated than misoprostol in patients taking nonsteroidal anti-inflammatory
      drugs (NSAIDs). In endoscopically proven gastro-oesophageal reflux disease,
      standard daily doses of the PPIs are more effective than H2-receptor antagonists
      for healing, and patients should receive a 4 to 8 week course of treatment. For
      severe reflux, with ulceration and/or stricture formation, a higher dose regimen
      (omeprazole 40 mg, lansoprazole 60 mg, pantoprazole 80 mg or rabeprazole 40 mg
      daily) appears to yield better healing rates. There is little evidence that PPIs
      lead to resolution of Barrett's oesophagus or a reduction of subsequent
      adenocarcinoma development, but PPIs are indicated in healing of any associated
      ulceration. In Zollinger-Ellison syndrome, PPIs have become the treatment of
      choice for the management of gastric acid hypersecretion.

PMID- 9777313
TI  - Amphotericin-B colloidal dispersion. A review of its use against systemic fungal
      infections and visceral leishmaniasis.
AB  - Formulation of amphotericin B with sodium cholesteryl sulphate alters the
      pharmacokinetic properties of the drug, particularly reducing its distribution to
      the kidneys. The antifungal activity in vitro of amphotericin B colloidal
      dispersion (ABCD) is similar to that of conventional amphotericin B (C-AmB)
      against true pathogenic organisms including Blastomyces, Coccidioides,
      Histoplasma and Paracoccidioides species and the opportunistic organisms such as
      Candida and Cryptococcus species. In animal models, ABCD was generally less
      effective than an identical dose of C-AmB, but overall was more effective because
      of its improved therapeutic index. Although ABCD appeared to be more effective
      than C-AmB in resolving infection and improving survival in patients with proven
      or probable invasive aspergillosis, the retrospective design of the study and the
      greater prevalence of neutropenia in patients treated with the conventional
      formulation necessitate cautious interpretation of the results. ABCD has been
      effective and seldom caused nephrotoxicity in patients with fungal infection who
      had previously failed to adequately respond or had developed renal toxicity with
      C-AmB. Similarly, ABCD was effective in patients with proven or suspected fungal
      infection after bone marrow transplantation. Preliminary results from a pilot
      study comparing ABCD and C-AmB in patients with neutropenia and persistent fever
      reported similar response rates with both formulations. ABCD is an effective
      treatment for visceral leishmaniasis in immunocompetent patients. In 1 study,
      about 12% of ABCD recipients discontinued the drug because of adverse events;
      infusion-related events were the most common cause of discontinuation. The renal
      tolerability of ABCD is better than that of C-AmB. ABCD appears to be an
      effective alternative to conventional amphotericin B in patients with invasive
      aspergillosis or visceral leishmaniasis and in those with proven or suspected
      systemic fungal infection who are intolerant of the conventional formulation or
      have pre-existing renal impairment. Preliminary data also suggest that ABCD is an
      alternative to C-AmB when used empirically in patients with neutropenia and
      fever. Nevertheless, the efficacy of ABCD compared with that of the conventional
      formulation has yet to be adequately demonstrated and the role of ABCD relative
      to that of liposomal and other lipid-based formulations has not been determined.
      CONCLUSIONS: ABCD, like other lipid-based and liposomal formulations of
      amphotericin B, has been designed to deliver the active drug to the target site,
      while reducing renal toxicity. The aim of increasing the therapeutic index
      compared with C-AmB has been achieved.

PMID- 9777314
TI  - Dexrazoxane. A review of its use as a cardioprotective agent in patients
      receiving anthracycline-based chemotherapy.
AB  - Dexrazoxane has been used successfully to reduce cardiac toxicity in patients
      receiving anthracycline-based chemotherapy for cancer (predominantly women with
      advanced breast cancer). The drug is thought to reduce the cardiotoxic effects of
      anthracyclines by binding to free and bound iron, thereby reducing the formation
      of anthracycline-iron complexes and the subsequent generation of reactive oxygen
      species which are toxic to surrounding cardiac tissue. Clinical trials in women
      with advanced breast cancer have found that patients given dexrazoxane (about 30
      minutes prior to anthracycline therapy; dexrazoxane to doxorubicin dosage ratio
      20:1 or 10:1) have a significantly lower overall incidence of cardiac events than
      placebo recipients (14 or 15% vs 31%) when the drug is initiated at the same time
      as doxorubicin. Cardiac events included congestive heart failure (CHF), a
      significant reduction in left ventricular ejection fraction and/or a > or = 2
      point increase in the Billingham biopsy score. These results are supported by the
      findings of studies which used control groups (patients who received only
      chemotherapy) for comparison. The drug appears to offer cardiac protection
      irrespective of pre-existing cardiac risk factors. In addition, cardiac
      protection has been shown in patients given the drug after receiving a cumulative
      doxorubicin dose > or = 300 mg/m2. It remains to be confirmed that dexrazoxane
      does not affect the antitumour activity of doxorubicin: although most studies
      found that clinical end-points (including tumour response rates, time to disease
      progression and survival duration) did not differ significantly between treatment
      groups, the largest study did show a significant reduction in response rates in
      dexrazoxane versus placebo recipients. Dexrazoxane permits the administration of
      doxorubicin beyond standard cumulative doses; however, it is unclear whether this
      will translate into prolonged survival. Preliminary results (from small nonblind
      studies) indicate that dexrazoxane reduces cardiac toxicity in children and
      adolescents receiving anthracycline-based therapy for a range of malignancies.
      The long term benefits with regard to prevention of late-onset cardiac toxicity
      remain unclear. With the exception of severe leucopenia [Eastern Cooperative
      Oncology Group (ECOG) grade 3/4 toxicity], the incidence of haematological and
      nonhaematological adverse events appears similar in patients given dexrazoxane to
      that in placebo recipients undergoing anthracycline-based chemotherapy. Although
      preliminary pharmacoeconomic analyses have shown dexrazoxane to be a cost
      effective agent in women with advanced breast cancer, they require confirmation.
      CONCLUSIONS: Dexrazoxane is a valuable drug for protecting against cardiac
      toxicity in patients receiving anthracycline-based chemotherapy. Whether it
      offers protection against late-onset cardiac toxicity in patients who received
      anthracycline-based chemotherapy in childhood or adolescence remains to be
      determined. Further clinical experience is required to confirm that it does not
      adversely affect clinical outcome, that it is a cost-effective option, and to
      determine the optimal treatment regimen.

PMID- 9777315
TI  - Milnacipran. A review of its use in depression.
AB  - Milnacipran is a cyclopropane derivative which acts by inhibiting noradrenaline
      (norepinephrine) and serotonin (5-hydroxytryptamine; 5-HT) reuptake at
      presynaptic sites; no postsynaptic receptor activity has been demonstrated. It is
      most commonly administered at a dosage of 50 mg twice daily for the treatment of
      major depressive disorder. Improvement usually occurs within 2 weeks of treatment
      initiation, but some patients do respond sooner. Most studies which evaluated
      milnacipran were of short (4 to 8 weeks) duration and results were not published
      in full with rigorous peer review. Nonetheless, the drug is significantly more
      effective than placebo for the treatment of in- or outpatients with moderate to
      severe major depressive disorder. Limited data suggest that it may prevent
      relapse and be effective for long term use, although this requires confirmation.
      Milnacipran 200 mg/day is generally not significantly different from
      amitriptyline 150 mg/day in terms of onset and efficacy. However, when doses are
      titrated (not a requirement for milnacipran), milnacipran 50 or 100 mg/day has a
      slower onset than the tricyclic antidepressant. At a dosage of 100 mg/day for 4
      to 12 weeks, milnacipran generally has similar efficacy to imipramine and
      clomipramine 150 mg/day, although milnacipran 50 to 150 mg/day had a faster onset
      of activity than imipramine 50 to 150 mg/day in Japanese patients. In a 6-month
      trial, milnacipran was less effective than clomipramine. Milnacipran 50 or 100 mg
      twice daily was as effective as fluoxetine 20 mg once daily or fluvoxamine 100 mg
      twice daily in 4- to 12-week studies. At a dosage of 50 then 100 mg daily it was
      also as effective as mianserin 30 then 60 mg daily in a 4-week study. However,
      when administered once daily (in the evening), milnacipran 100 mg/day was not as
      effective as fluoxetine 20 mg/day after 6 weeks. The drug is generally well
      tolerated, producing no more adverse events (including anticholinergic events)
      than placebo, selective serotonin reuptake inhibitors or mianserin and fewer
      adverse events than tricyclic antidepressants in clinical trials. However,
      dysuria has been reported in 7% of male patients receiving milnacipran.
      CONCLUSIONS: Data from predominantly short term trials suggest that milnacipran
      generally has similar efficacy to tricyclic antidepressants and SSRIs. Although
      further published data are required to confirm its efficacy, good tolerability
      profile and pharmacokinetic profile which suggests a low potential for drug
      interactions, milnacipran should be considered a promising agent for the
      treatment of patients with major depressive disorder.

PMID- 9777316
TI  - Domperidone. A review of its use in diabetic gastropathy.
AB  - Domperidone is a selective antagonist at peripheral dopamine D2 receptors, with
      gastroprokinetic and antiemetic properties. It increases the frequency and
      duration of antral and duodenal contractions, thus decreasing/improving transit
      time of food through the gastrointestinal tract. Gastric emptying of liquids and
      solids is significantly improved with oral domperidone 40 to 120 mg/day in
      patients with diabetic gastropathy. Oral domperidone 40 to 80 mg/day
      significantly decreased the severity of symptoms of gastropathy from baseline
      values in 66 to 88% of patients with type 1 (insulin-dependent) or insulin
      requiring diabetes mellitus. Double-blind withdrawal of domperidone from patients
      who had responded previously led to greater deterioration of symptoms in patients
      with delayed gastric emptying than in those who continued receiving the drug.
      Quality of life was significantly improved in patients who showed a symptomatic
      response to domperidone. The administration of domperidone 40 to 120 mg/day
      significantly reduced hospitalisation rates in patients with gastropathy. The
      symptomatic improvement with domperidone 80 mg/day was similar to that seen with
      cisapride 40 mg/day or metoclopramide 40 mg/day, and therapeutic benefits seen in
      symptoms of gastropathy were maintained with domperidone for up to 12 years.
      Domperidone 40 to 80 mg/day may be effective in patients who are refractory to
      metoclopramide, and a combination of domperidone 80 mg/day with cisapride 80
      mg/day may improve some symptoms in patients who do not respond to either agent
      alone. Domperidone 40 to 120 mg/day was well tolerated for periods up to 12 years
      in trials in patients with diabetic gastropathy. Adverse events with domperidone
      80 mg/day were similar to those seen in placebo recipients and significantly
      fewer than in patients receiving metoclopramide 40 mg/day. Although significant
      elevation of plasma prolactin levels (unrelated to dosage and duration of
      treatment) occurred in all domperidone recipients, prolactin-related adverse
      events were observed in only 10 to 20% of patients. CONCLUSIONS: The available
      data suggest that domperidone 40 to 80 mg/day is an effective agent for the
      management of symptoms of gastropathy in patients with type 1 diabetes mellitus.
      In addition, it may provide symptom improvement in patients with gastropathy
      refractory to other gastroprokinetic agents. Domperidone maintains efficacy in
      the long term (up to 12 years) and appears to have a better tolerability profile
      than metoclopramide 40 mg/day.

PMID- 9777319
TI  - Early intervention in obesity: implications for impaired glucose tolerance and
      type II diabetes.

PMID- 9777318
TI  - Levofloxacin. Its use in infections of the respiratory tract, skin, soft tissues
      and urinary tract.
AB  - Levofloxacin, the optically pure levorotatory isomer of ofloxacin, is a
      fluoroquinolone antibacterial agent. Like other fluoroquinolones, it acts on
      bacterial topoisomerase and has activity against a broad range of Gram-positive
      and Gram-negative organisms. Levofloxacin also appears to have improved activity
      against Streptococcus pneumoniae compared with ciprofloxacin or ofloxacin.
      Levofloxacin distributes well and achieves high levels in excess of plasma
      concentrations in many tissues (e.g., lung, skin, prostate). High oral
      bioavailability allows switching from intravenous to oral therapy without dosage
      adjustment. In patients with mild to severe community-acquired pneumonia
      receiving treatment for 7 to 14 days, oral levofloxacin was similar in efficacy
      to amoxicillin/clavulanic acid, and intravenous and/or oral levofloxacin was
      superior to intravenous ceftriaxone and/or oral cefuroxime axetil. With
      levofloxacin use, clinical success (clinical cure or improvement) rates were 87
      to 96% and bacteriological eradication rates were 87 to 100%. In the 5- to 10-day
      treatment of acute exacerbations of chronic bronchitis, oral levofloxacin was
      similar in efficacy to oral cefuroxime axetil or cefaclor. Levofloxacin resulted
      in clinical success in 78 to 94.6% of patients and bacteriological eradication in
      77 to 97%. Oral levofloxacin was also similar in efficacy to
      amoxicillin/clavulanic acid or oral clarithromycin in patients with acute
      maxillary sinusitis treated for 7 to 14 days. Equivalence between 7- to 10-day
      therapy with oral levofloxacin and ciprofloxacin was seen in patients with
      uncomplicated skin and soft tissue infections. Clinical success was seen in 97.8
      and 96.1% of levofloxacin recipients and bacteriological eradication in 97.5 and
      93.2%. Complicated urinary tract infections, including pyelonephritis, responded
      similarly well to oral levofloxacin or ciprofloxacin for 10 days or lomefloxacin
      for 14 days. Clinical success and bacteriological eradication rates with
      levofloxacin occurred in 92 to 93.3% and 93.6 to 94.7% of patients. CONCLUSIONS:
      Levofloxacin can be administered in a once-daily regimen as an alternative to
      other fluoroquinolones in the treatment of infections of the urinary tract, skin
      and soft tissues. Its more interesting use is as an alternative to established
      treatments of respiratory tract infections. S. pneumoniae appears to be more
      susceptible to levofloxacin than to ciprofloxacin or ofloxacin. Other newer
      fluoroquinolone agents that also have enhanced in vitro antipneumococcal activity
      may not share the well established tolerability profile of levofloxacin, which
      also appears to improve on that of some older fluoroquinolones.

PMID- 9777320
TI  - Relationship between impaired glucose tolerance, non-insulin-dependent diabetes
      mellitus and obesity.
AB  - Plasma glucose concentration is the best predictor for the development of non
      insulin-dependent diabetes mellitus (NIDDM). However, obesity is also a
      recognized risk factor for development of the disease, and is easier to track
      over time. Thus obesity could be of considerable clinical importance as a
      predictor of diabetes. Studies have shown that the degree of overweight, the
      change in weight and the duration of overweight are all separate predictors of
      diabetes. The British Regional Heart Study showed that an increasing body mass
      index (BMI) was associated with increased risk of developing diabetes, even at
      BMI values not considered obese. A separate study showed that weight gain
      increased the risk of diabetes independently of BMI, while weight loss decreased
      the risk. The duration of obesity was also an important factor in developing
      NIDDM. A long duration increased the risk of diabetes, irrespective of the final
      BMI value. The effects of obesity on insulin action have also been investigated.
      Studies have shown that insulin sensitivity is inversely related to insulin
      secretion, with a disproportionate increase in insulin secretion seen with
      decreasing sensitivity. A recent European study showed that the prevalence of
      both insulin hypersecretion and insulin resistance increased with increasing BMI.
      Thus, in obesity, higher insulin levels are necessary to maintain glucose
      tolerance, leading to increased stress on the beta-cells. In obese individuals,
      weight loss improved insulin sensitivity in proportion to the degree of weight
      loss, leading to decreased insulin secretion. Weight loss can therefore, at least
      in the short term, act to decrease the risk of developing diabetes by reducing
      insulin resistance, and thus relieving beta-cell stress, the factor ultimately
      responsible for hyperglycaemia in predisposed individuals.

PMID- 9777321
TI  - Determinants for the progression from impaired glucose tolerance to non-insulin
      dependent diabetes mellitus.
AB  - The World Health Organization distinguishes among non-diabetic persons a form of
      glucose intolerance defined as impaired glucose tolerance (IGT). The main reason
      for considering IGT as a diagnostic entity is its prognostic value for the
      development of non-insulin-dependent diabetes mellitus (NIDDM). However, the use
      of one or two oral glucose tolerance tests (OGTT) for the definition of IGT and
      the large variability of the 2-h glucose level may explain the wide range of the
      incidence rates reported for NIDDM in subjects with IGT. It is evident that the
      pathogenesis of diabetes is still poorly understood. Both insulin resistance and
      impaired function of the beta-cell are thought to be important contributing
      factors in the development of diabetes. The 2-h post-load glucose level from the
      OGTT is most powerful for the prediction of the development of NIDDM. In
      addition, a fasting hyperinsulinaemia and a low glucose removal rate, both
      reflecting insulin resistance, were found to be associated with a higher risk for
      the progression of NIDDM. In the San Antonio Study and in the Hoorn Study high
      fasting proinsulin levels, reflecting beta-cell dysfunction, were associated with
      progression to NIDDM. Lipid levels did not predict progression to NIDDM in most
      studies. A two-step model for the development of NIDDM is hypothesized. The first
      step, the transition from normal to impaired glucose tolerance, is assumed to
      depend mainly on the presence of insulin resistance. The second step, progressing
      from IGT to diabetes, although accompanied by some further worsening of insulin
      resistance, is thought to be primarily dependent on the development of beta-cell
      dysfunction.

PMID- 9777322
TI  - Relationship between obesity and the increased risk of major complications in non
      insulin-dependent diabetes mellitus.
AB  - Obesity and non-insulin-dependent diabetes mellitus (NIDDM) are closely linked.
      They frequently occur together in patients, and body mass index (BMI) is the
      strongest risk factor for the development of NIDDM. Both obesity and NIDDM are
      also major causes of morbidity and mortality from atherogenic macrovascular
      disease, and they are independent risk factors for coronary heart disease. The
      risk of developing NIDDM and cardiovascular disease is affected by the regional
      distribution of body fat. Visceral obesity is associated with a higher degree of
      risk than peripheral obesity. The metabolic and circulatory changes associated
      with visceral obesity lead to the development of insulin resistance and increased
      lipoprotein synthesis. For example, the change in the population profile of
      lipoproteins in the blood, and alterations in the levels of oxidative stress lead
      to an increased cardiovascular and macrovascular risk. The changes in lipid
      metabolism also affect haemorrheological function. They have been linked to
      decreased fibrinolysis (a serious cardiovascular risk factor) through elevated
      levels of plasminogen activator inhibitor factor, high blood viscosity, and
      increased erythrocyte aggregability. Increased BMI also appears to be associated
      with endothelial dysfunction, which is a major factor in atheroma plaque
      formation and development of thrombosis. Visceral obesity therefore adds a
      significant burden to the already increased cardiovascular risk inherent in
      NIDDM. However, even moderate weight loss may successfully reverse the majority
      of changes seen with visceral obesity.

PMID- 9777324
TI  - Pharmacological intervention: the antidiabetic approach.
AB  - Impaired glucose tolerance (IGT) progresses to non-insulin-dependent diabetes
      mellitus (NIDDM) in many but not all IGT subjects. It remains unsettled whether
      long-term antidiabetic (i.e. antihyperglycaemic) pharmacotherapy delays the
      development of NIDDM, and whether such treatment influences macrovascular
      morbidity and mortality. This report summarizes the results from long-term (> 4
      years) antihyperglycaemic interventions addressing these issues. In an American
      study, tolbutamide (0.5 g 2-3 times daily) promoted a 4-year improvement of
      glucose tolerance in young, non-obese, mildly diabetic asymptomatic subjects who
      apparently comprised a mixture of IGT and NIDDM. In a Swedish 5-year study on 178
      survivors of myocardial infarction, of whom 79 had intravenous IGT, tolbutamide
      treatment was associated with improved glucose tolerance, reduced triglyceride
      levels, and improved 18-month survival. A British 5-year study on a subgroup of
      about 200 middle-aged men from the Whitehall cohort indicated that phenformin (50
      mg once daily) did not influence the deterioration of glucose levels. In a 10
      year British study, 241 middle-aged men and women were 4-square randomized to
      control, weight reduction, placebo and tolbutamide (0.5 g twice daily). A non
      lasting reduction of arterial disease was recorded in those on tolbutamide. No
      reduction of NIDDM development was seen. In a Swedish 10-year study on middle
      aged men with IGT, follow-up comprised 59 controls, 98 on diet advice with or
      without placebo, and 23 on tolbutamide (0.5 g three times daily) added to diet
      advice. A total of 29% developed NIDDM among controls and 13% in the diet group.
      In contrast, no subject maintaining tolbutamide treatment developed NIDDM.
      Moreover, the tolbutamide-treated subjects had reduced blood pressure,
      triglyceride and cholesterol levels, as well as fewer macrovascular
      complications. Recently, a lower mortality rate at 22 years after the start of
      tolbutamide treatment has been recorded. To summarize, treatment with insulin
      releasing drugs might help to reduce the development of NIDDM and macrovascular
      disease in IGT subjects. However, further studies are needed to verify or refute
      this notion.

PMID- 9777323
TI  - Diet, exercise and behavioural intervention: the nonpharmacological approach.
AB  - Behaviour is an important factor in both the aetiology and treatment of obesity.
      Successful long-term weight management ultimately depends on the ability of
      patients to change their behaviour patterns, particularly with regard to diet and
      exercise. Many patients find such changes extremely difficult to initiate and
      maintain. The failure to properly address behavioural modification is part of the
      reason why so many weight loss programmes cannot produce long-term weight loss,
      even though initial weight loss is often achieved with relative ease. Four
      examples of lifestyle changes are discussed in this paper: exercise; relapse
      prevention; the concept of a reasonable weight; and attribution theory.
      Behavioural therapy should be an integral part of a multifaceted approach for
      managing obesity and associated conditions, such as type II (non-insulin
      dependent) diabetes.

PMID- 9777317
TI  - Omeprazole. A review of its use in Helicobacter pylori infection, gastro
      oesophageal reflux disease and peptic ulcers induced by nonsteroidal anti
      inflammatory drugs.
AB  - Omeprazole is a well studied proton pump inhibitor that reduces gastric acid
      secretion. This review examines its use in Helicobacter pylori infection, gastro
      oesophageal reflux disease (GORD) with or without oesophagitis and
      gastrointestinal damage caused by nonsteroidal anti-inflammatory drugs (NSAIDs).
      Optimal omeprazole regimens for anti-H. pylori therapy are those that administer
      the drug at a dosage of 40 mg/day (in 1 or 2 divided doses) for 7, 10 or 14 days
      in combination with 2 antibacterial agents. As a component of 3-drug regimens in
      direct comparative studies, omeprazole was at least as effective as lansoprazole,
      pantoprazole, bismuth compounds and ranitidine. However, a meta-analysis suggests
      that triple therapies with omeprazole are more effective than comparable regimens
      containing ranitidine, lansoprazole or bismuth. Omeprazole also appears to be
      successful in triple therapy regimens used in children with H. pylori infection.
      In patients with acute GORD with oesophagitis, omeprazole is at least as
      effective as lansoprazole or pantoprazole in promoting healing, and superior to
      ranitidine, cimetidine or cisapride in oesophagitis healing and symptom relief.
      Omeprazole was similar to lansoprazole and superior to ranitidine in preventing
      oesophagitis relapse in patients with all grades of oesophagitis, but may be
      superior to lansoprazole or pantoprazole in patients with more severe disease.
      More patients with symptomatic GORD without oesophagitis experienced symptom
      relief after short term treatment with omeprazole than with ranitidine, cisapride
      or placebo, and symptoms were more readily prevented by omeprazole than by
      cimetidine or placebo. Omeprazole was effective in healing and relieving symptoms
      of reflux oesophagitis in children with oesophagitis refractory to histamine H2
      receptor antagonists. Omeprazole is superior to placebo in preventing NSAID
      induced gastrointestinal damage in patients who must continue to take NSAIDs. It
      is also similar to misoprostol and superior to ranitidine in its ability to heal
      NSAID-induced peptic ulcers and erosions, and superior to misoprostol, ranitidine
      or placebo in its ability to prevent relapse. In long and short term studies,
      omeprazole was well tolerated, with diarrhoea, headache, dizziness, flatulence,
      abdominal pain and constipation being the most commonly reported adverse events.
      Usual omeprazole dosages, alone or combined with other agents, are 10 to 40
      mg/day for adults and 10 to 20 mg/day for children. CONCLUSIONS: Omeprazole is a
      well studied and well tolerated agent effective in adults or children as a
      component in regimens aimed at eradicating H. pylori infections or as monotherapy
      in the treatment and prophylaxis of GORD with or without oesophagitis or NSAID
      induced gastrointestinal damage.

PMID- 9777325
TI  - Pharmacological intervention: the antiobesity approach.
AB  - Reduction in overweight and obesity management have been shown to be important in
      the treatment of diabetes. Even modest weight loss produces important metabolic
      benefits if maintained over the long term. Thus a pharmacotherapeutic agent that
      could produce a maintained weight loss, and had a good safety profile, would
      revolutionize the treatment of type II (non-insulin-dependent) diabetes. Two
      obesity management agents, orlistat and sibutramine, are expected shortly for the
      long-term treatment of obesity. These agents have been shown to be effective in 1
      2-year-long studies in obese, non-diabetic patients. They produced significant
      improvements in weight loss compared with placebos. The efficacy of these obesity
      management agents has also been demonstrated in short-term studies in patients
      with type II diabetes. As yet, however, few studies have investigated the long
      term effects of these treatments in diabetic patients. Obese patients with type
      II diabetes receiving 12 months of dexfenfluramine therapy showed greater
      reductions in weight, fasting blood glucose and HbA1c levels than the controls. A
      1-year study of orlistat treatment for patients with type II diabetes revealed
      substantial benefits in glycaemic control, even though weight loss was only
      moderate. A 1-year treatment with orlistat also substantially prevented the
      conversion of impaired glucose tolerance into type II diabetes (conversion rate
      2.6% in the orlistat group versus 10.4% in the placebo group). Encouraging
      results have also been reported from studies on orlistat and sibutramine in non
      diabetics, with beneficial effects seen for weight loss and other diabetes risk
      factors. Antiobesity pharmacotherapy therefore appears to offer a realistic
      option for the prevention of diabetes, although further studies are required to
      determine its efficacy.

PMID- 9777326
TI  - Strong association between DQA1/DQB1 genotype and early-onset IDDM in Chinese:
      the association is with alleles rather than specific residues.
AB  - We report on the role of HLA-DQA1 and DQB1 alleles in determining susceptibility
      to insulin-dependent diabetes mellitus (IDDM) in Hong Kong Chinese and
      investigate whether these alleles affect the age of onset of the disease. We
      studied 76 unrelated Chinese patients and 250 controls. There was no apparent
      predisposing effect of non-aspartic acid residues at position 57 of the DQ beta
      chain (Asp57-) but there was an excess of homozygous genotypes containing
      arginine at position 52 of the DQ alpha chain (Arg52+). This excess was mainly
      attributable to the genotype DQA1*0301/DQA1*05011 in early-onset disease. There
      was a significant excess of heterodimers of DQ alpha and DQ beta carrying Arg52+
      and Asp57- in both early-onset and late-onset disease, but the excess in early
      onset disease was mainly attributable to a single heterodimer formed by
      DQA1*05011 and DQB1*0201. Of three DQA1/DQB1 genotypes containing a double dose
      of Arg52+ and Asp57-, only one had a strong association with both early-onset and
      late-onset disease. We show that early-onset IDDM and late-onset IDDM in Chinese
      may be separated on the basis of their associated DQA1 and DQB1 genotypes and we
      conclude that previously reported associations of IDDM with Arg52+ and Asp57-
      residues in Chinese are secondary to specific combinations of DQA1 and DQB1
      alleles. We also show that DRB1 molecules play a distinct role in determining
      susceptibility to early-onset IDDM but the greatest effect is exerted by specific
      DR/DQ genotypic combinations.

PMID- 9777327
TI  - HLA antigens and haplotypes in IgA-deficient Brazilian paediatric patients.
AB  - In the present study we determined the HLA-A, B and DR antigenic and haplotypic
      frequencies in unrelated Brazilian Caucasian paediatric patients with IgA
      deficiency (IgA-D). Out of 17 IgA-D subjects typed for HLA A and B specificities,
      12 (71%) presented B8 and/or B14; of 15 patients also typed for HLA-DR
      specificities, 14 (93%) were positive for at least one of the HLA markers
      previously reported to be associated with IgA-D, i.e. B8, B14, DR1, DR3 or DR7.
      The haplotypes B8, DR3, B14, DR1 and B13, DR7 were present in 43, 21 and 14% of
      the cases, respectively, while they have a frequency in the general population of
      2, 2 and 1%, respectively. The concomitant association with the three IgA
      associated haplotypes found in our study probably reflects the admixture of
      European genetic influences present in the Brazilian Caucasian population of Sao
      Paulo.

PMID- 9777328
TI  - Description of a new kind of MHC DNA sequence in Saguinus oedipus (cotton-top
      tamarin).
AB  - The MHC class I genes of the New World primate the cotton-top tamarin (Saguinus
      oedipus) are an exception to the high polymorphism and variability usually
      displayed by this multigene family. In the present work, the cloning and
      sequencing of a new pseudogene, tentatively named Saoe-Mhc-N4, in this primate
      species are reported. This new sequence has two characteristic deletions at exon
      2, making it very unlikely that any putative protein from this sequence was an
      antigen-presenting molecule. Comparison of intron 1, intron 2, partial exon 1,
      exon 2 and partial exon 3 showed little similarity with those of classical class
      I genes and pseudogenes in S. oedipus and in other primates. Phylogenetic
      analysis grouped this Saoe-Mhc-N4 sequence with other pseudogenes in S. oedipus.
      Thus, it seems that Saoe-Mhc-N4 is an inactivated gene or a pseudogene which has
      been originated by the common process of duplication and subsequent inactivation
      of MHC class I loci in this primate species.

PMID- 9777329
TI  - The distribution of HLA-DRB alleles in ulcerative colitis patients in Turkey.
AB  - Recently described distinct associations of HLA class II genes with ulcerative
      colitis (UC) suggest a genetic heterogeneity for disease susceptibility. In this
      study, HLA-DRB alleles of UC patients (n = 59) from Turkey were investigated and
      compared with healthy controls (n = 244). Using molecular genotyping by
      polymerase chain reaction (PCR) and sequence-specific oligonucleotide
      hybridization, we have shown a positive association of UC patients with the HLA
      DRB1*1502 allele (10/59 vs. 16/244; P = 0.02; OR: 2.9) and a negative association
      with the DRB1*13 allele (7/59 vs. 64/244; P = 0.03; OR: 0.38) compared to
      controls. HLA-DRB1*0701 was significantly increased in perinuclear antineutrophil
      cytoplasmic antibody (pANCA)-positive UC patients compared to pANCA-negative
      patients (8/32 vs. 0/27; P = 0.005), whereas DRB1*1502 was observed more
      frequently in pANCA-negative patients (8/27 vs. 2/32; P = 0.03). These results
      extended the reported positive association of DRB1*1502 with UC to another
      population and supported the genetic susceptibility associated with HLA genes for
      disease development.

PMID- 9777330
TI  - HLA class II (DRB1, DQA1 and DQB1) associated genetic susceptibility in Iranian
      multiple sclerosis (MS) patients.
AB  - The association of HLA class II alleles with multiple sclerosis (MS) has been
      amply documented. In the present study, the role of HLA class II (DRB1, DQA1 and
      DQB1) alleles and haplotypes was investigated in 43 unrelated Iranian chronic
      progressive multiple sclerosis (CP-MS) patients compared with 100 healthy
      individuals. HLA typing for DRB1, DQA1 and DQB1 was performed by restriction
      fragment length polymorphism (RFLP). Subtypes of DR4, DR15 and DR16 were defined
      using polymerase chain reaction (PCR) amplification with sequence-specific
      primers (PCR-SSP). The results show that, among DR2-positive MS patients and the
      control group, a positive association with the DRB1*1503, DQA1*0102, DQB1*0602
      haplotype (21% vs. 2.7%, P = 0.057, RR = 9.8) and a negative association with the
      most frequent DR15 haplotype in the control group, DRB1*15021, DQA1*0103,
      DQB1*0601 (7% vs. 24.3%, P = 0.001), were observed. No significant association
      was found with the analysed HLA-DRB1, DQA1 and DQB1 alleles.

PMID- 9777331
TI  - Molecular cloning and sequencing of feline stromal cell-derived factor-1 alpha
      and beta.
AB  - The stromal cell-derived factor-1 alpha and beta (SDF-1 alpha/beta) are the
      ligands of fusin/CXCR4, the co-receptors of human immunodeficiency virus type 1
      and the feline immunodeficiency virus. We cloned the cDNA of feline SDF-1
      alpha/beta. The open reading frames of feline SDF-1 alpha/beta were 267/279 base
      pairs and encoded 89/93 amino acid residues.

PMID- 9777332
TI  - Complete cDNA sequence of the HLA-DRB1*09012 allele.
AB  - Sequencing studies of HLA class II molecules have focused almost exclusively on
      exon 2. In this study the complete cDNA sequence of the DRB1*09012 allele is
      reported for the first time. This sequence was previously only partially
      published. In the DR9 antigen, two synonymous allelic variants (DRB1*09011 and
      09012) were officially recognized, though it was later found that the first one
      contained an error and both sequences were, thus, identical.

PMID- 9777334
TI  - Complement C4B null allele status confers risk for systemic lupus erythematosus
      in a Spanish population.
AB  - Genetic susceptibility to systemic lupus erythematosus (SLE) may vary amongst
      different populations. In UK patients, genes encoded in the HLA class II
      (DQA*0501/DRB1*0301) and class III [C4A*Q0 and tumour necrosis factor (TNF)
      polymorphisms] subregions appear to contribute to disease susceptibility. We have
      examined HLA-DRB1, C4 and TNF microsatellites in 50 Spanish SLE patients and 48
      matched controls. HLA-DRB1*0301 was increased in patients but did not achieve
      statistical significance (41% vs. 25.5%). C4A*Q0 was not increased in patients,
      but C4B*Q0 allele frequency was significantly increased compared with the
      controls (29% vs. 6%; OR: 6.0). TNF c2 microsatellite allele frequency was also
      increased in SLE patients. The C4B null allele (C4B*Q0) appears to play an
      important role in SLE susceptibility in the Spanish population.

PMID- 9777335
TI  - Nomenclature for factors of the HLA system, update January 1998.

PMID- 9777333
TI  - Lack of HLA-G soluble isoforms in Graves-Basedow thyrocytes and complete cDNA
      sequence of the HLA-G*01012 allele.
AB  - The presence of HLA-G mRNA has been studied in thyroid follicular cells from
      autoimmune patients with Graves' disease. Investigating the possible role of the
      expression of the HLA-G gene in tissue inflammation, we have found four of the
      six HLA-G mRNA isoforms described: G1, G2, G3 and G4, but not the soluble ones G5
      and G6. Soluble G isoforms may be responsible for inducing tolerance and
      inflammation control and their absence in autoimmune thyroid follicular cells may
      induce failure of such control. In addition, the complete coding sequence of HLA
      G*01012 has been obtained from thyrocytes and it shows only four synonymous
      changes with respect to the HLA-G*01011 allele; this further supports the
      existence of an evolutionary pressure for invariance on HLA-G genes.

PMID- 9777336
TI  - Nomenclature for factors of the HLA system, update February 1998.

PMID- 9777337
TI  - Nomenclature for factors of the HLA system, update March 1998.

PMID- 9777338
TI  - Mutation analysis of the HLA-H gene in French hemochromatosis patients, and
      genetic counseling in families.
AB  - Mutation analysis of the HLA-H gene in French hemochromatosis patients and
      genetic counseling in families: Genotype analysis of 61 hemochromatosis patients
      living in France and 126 controls confirms that the disease is strongly
      associated with homozygosity for the mutation C282Y of the HLA-H gene: in our
      sample 67.2% patients, and none of the controls, carry two copies of the C282Y
      mutation; the frequency of the C282Y allele in a control population is 3.97%. A
      second variant (H63D) at the HLA-H gene is somehow more enriched (8.2%) in
      patient chromosomes that do not carry the C282Y mutation. The C282Y mutation was
      used in 10 hemochromatosis families for genetic counseling.

PMID- 9777340
TI  - Further delineation of the KBG syndrome.
AB  - Further Delineation of the KBG syndrome: We present a mother and her daughter
      with clinical features of KBG syndrome, including mild mental retardation,
      distinct facial features, macrodontia and skeletal anomalies. In the daughter, a
      heart defect (ventricular septal defect) was present.

PMID- 9777341
TI  - Ophthalmo-acromelic syndrome (Waardenburg) with split hand and polydactyly.
AB  - We report on a boy with anophthalmia, split hand, oligodactyly, syndactyly and
      polydactyly: These features are consistent with the diagnosis of the ophthalmo
      acromelic syndrome (Waardenburg). However, the hand anomalies have not been
      reported yet. This observation helps to extend the wide range of expressivity of
      this rare syndrome.

PMID- 9777339
TI  - The Catel-Manzke syndrome in a female infant.
AB  - Catel-Manzke syndrome in a female infant: We describe a girl with typical
      features of the Catel-Manzke syndrome. Although most cases described are boys, X
      linked inheritance is not very likely now at least four females with this
      syndrome have been described.

PMID- 9777342
TI  - Bjornstad syndrome in a patient with mental retardation.
AB  - Bjornstad syndrome in a patient with mental retardation: Pili torti or twisted
      hair can appear as an isolated defect, in association with other ectodermal
      defects, in association with other clinical features or can be acquired.
      Bjornstad syndrome is a rare condition with apparent autosomal recessive
      inheritance, characterized by hearing loss and twisted hairs (pili torti). All
      patients with Bjornstad syndrome reported thusfar have normal intelligence. We
      report on a patient with severe mental retardation and review the literature.

PMID- 9777343
TI  - Lethal hypophosphatasia, spur type: case report and fetopathological study.
AB  - Lethal hypophosphatasia, spur type: case report and fetopathological study:
      Hypophosphatasia (HP) is characterised by severe undermineralisation of the
      skeleton owing to deficiency of tissue nonspecific alkaline phosphatase.
      Clinically a perinatal, infantile, childhood and adult type is distinguished.
      Clinical signs in the perinatal type of HP show considerable overlap with other
      skeletal dysplasias such as osteogenesis imperfecta type IIA and type IIC, and
      achondrogenesis type IA. If present, "spurs" of the limbs are diagnostic for HP.
      We present a prenatally diagnosed case of HP and discuss the differential
      diagnosis based on clinical, radiological and pathological findings. Our findings
      indicate that two types of spurs can be distinguished in hypophosphatasia:
      midshaft type and joint type.

PMID- 9777344
TI  - Spasticity, mental retardation, macrocephaly and distinct craniofacial
      appearance: confirmation of a new subtype of complicated spastic paraplegia?
AB  - Spasticity, mental retardation, macrocephaly and distinct craniofacial
      appearance: confirmation of a new subtype of complicated spastic paraplegia?: In
      this report, we describe a 30-year-old female with mental retardation, spastic
      paresis, epilepsy, macrocephaly and distinct craniofacial appearance. Probably,
      she suffers from the same condition as the two sibs described by Fryns et al., in
      1994 (2).

PMID- 9777345
TI  - Localization by FISH of centric fission breakpoints in a de novo trisomy 9p
      patient with i(9p) and t(9q;11p).
AB  - Localization by FISH of centric fission breakpoints in a de novo trisomy 9p
      patient with i(9p) and t(9q;11p): In this report we present a 38 year-old,
      severely mentally retarded female with 9p trisomy due to isochromosome 9p, i(9p),
      formation and translocation of the long arm of the rearranged chromosome 9 onto
      the telomere region of the short arm of chromosome 11: karyotype: 46, XX, -9, 
      11, +i(9p), +der(11) t(9;11) (q12;p15.5). C-banding showed that the i(9p) was
      monocentric and that der(11) had an additional C-band at the t(9q;11p) junction.
      The centric rearrangements were further identified by fluorescence in situ
      hybridisation (FISH) using a panel of chromosome 9 (peri)centric DNA probes.
      Analysis with probe pG-Xbal 1/340 (locus D4Z1), detecting the satellite subfamily
      at the centromeres of chromosomes 4 and 9, revealed small signals at the primary
      constriction of i(9p) but no signals at the breakpoint junction of the t(9q;11p).
      Further analysis using respectively chromosome 9 classical satellite probe (locus
      D9Z1), that consists of beta satellite sequences and pHuR98 probe (locus D9Z3)
      which detects satellite 3 DNA, localized to the 9qh region, both revealed
      translocation of these DNA sequences to the breakpoint of the t(9;11) junction.
      By using a 3'biotinylated oligonucleotide (TTAGGG)7 probe, no evidence was found
      for the presence of interstitial telomeric repeats at the t(9q;11p) breakpoint
      junction indicating that this derivative chromosome is the result of a reciprocal
      translocation with loss of telomeric regions including terminal 11p15.5-->pter.
      Our results provide evidence that the misdivision process that occurs on the
      chromosome 9 centric region results either from breakage in the alphoid DNA
      arrays or at the junction between alphoid and DNA regions.

PMID- 9777346
TI  - Catch 22--microdeletion 22q11 screening in patients with congenital heart
      defects.

PMID- 9777347
TI  - Trisomy 9p and tetrasomy 9p: a unique, clinically recognisable syndrome.

PMID- 9777348
TI  - Sudden death in children with Prader-Willy syndrome: a call for collaboration.

PMID- 9777349
TI  - [Genetic control of the early stages of cardiac development in vertebrates].
AB  - An attempt is made to summarize the main stages of the determination and
      specification of the heart in chicken, mouse, and rat embryos and to show what is
      currently known about the genes that participate in heart formation at early
      developmental stages in vertebrates.

PMID- 9777351
TI  - [Genetic alterations in the region of the p53 gene on human chromosome 17 in
      colorectal cancer].
AB  - Most colorectal tumors are characterized, among other genetic alterations, by
      allele loss of the genes located on the short arm of chromosome 17 (17p13.1),
      including the p53 suppressor gene. In ovarian and mammary-gland tumors, deletions
      of another candidate tumor-suppressor gene, located in the 17p13.3 chromosome
      region, were observed. We analyzed allele losses in the loci of the short arm of
      chromosome 17 (YNZ22, MCT35.1, and the p53 gene) in colorectal-cancer patients
      from the former Soviet Union. Tumors with cytogenetic alterations in 17p and/or
      with a detected loss of heterozygosity at the YNZ22 (D17S30) locus were examined
      for allele losses in the p53 gene using two polymorphic sites. Different methods
      revealed alterations on 17p in 24 (48%) out of 50 patients with colorectal
      carcinomas. In all tumors with an allele loss of the YNZ22 marker (15 out of 44
      informative cases), which was detected by means of PCR, allele loss of the p53
      gene was found (12 out of 15 informative cases). In 5 out of 13 tumors with
      cytogenetic alterations in 17p, allele loss of the p53 gene was found, with the
      YNZ22 marker being unaffected. In one of these tumors, the i(17q) marker was
      found, and in the remaining four tumors, 17p translocations were detected. In 4
      out of 5 tumors with translocations affecting 17p, the t(17;20)(q21;p12)
      translocation was detected. The informativeness of the screening for 17p
      translocations, using PCR for the YNZ22 locus, and the reasons for discrepancy
      between the data of PCR and cytogenetic analyses are discussed.

PMID- 9777350
TI  - [Comparison of the synonymous and non-synonymous substitution rates in various
      regions of the neuraminidase and hemagglutinin genes of the influenza A virus].
AB  - A new, statistically justified approach was used to estimate the synonymous and
      non-synonymous substitution rates in several antigenic variants of influenza
      virus surface proteins. The rates were compared for antigenic and nonantigenic
      regions of neuraminidase and hemagglutinin, as well as for neuraminidase surface
      and internal amino acids identified by X-ray analysis. For neuraminidase, the
      estimation was performed for the first time. The non-synonymous substitution rate
      was shown to be significantly higher in antigenic than in nonantigenic sites.
      However, neither subsample of antigenic sites displayed a fixation rate of non
      synonymous substitutions higher than that of synonymous substitutions, which
      would confirm the effect of positive selection on these sites and argue against a
      neutral evolution character. Specific features of methods used to estimate the
      substitution fixation rates and problems in their interpretation are discussed.

PMID- 9777352
TI  - [Formation of deletional derivatives of the Ti-plasmid pGV3850 in a conjugative
      transfer from Agrobacterium tumefaciens to Escherichia coli].
AB  - The process of the transfer of the Ti-plasmid vector pGV3850 with the plasmid
      pBR322 inserted into the T-DNA region from Agrobacterium tumefaciens to a non
      plasmid strain of Escherichia coli was studied. The transferred Ti-plasmid was
      found to be exposed to deletions and formed a wide range of derivatives with a
      size ranging from 3-4 kb to 50 kb, maintained in E. coli due to ColE1-replicon.
      The Ti-plasmid is also inserted into the chromosome of the recipient bacterium
      with at least a 100-fold lower frequency than the formation of deletional
      derivatives. It was shown that the induction of vir genes controlling the
      transfer of T-DNA into plants has no appreciable effect on the efficiency of
      obtaining transconjugates in mating with E. coli. The deletion of the genetic
      material of megaplasmids with the inserted functional site OriV ColE1, as a
      result of the conjugative transfer from cells of different bacteria to the cells
      of E. coli, was proposed for molecular cloning.

PMID- 9777353
TI  - [Role of additional binding sites for the CytR protein in the regulation of
      Escherichia coli udp gene expression].
AB  - The nucleotide sequence of a 1000-bp fragment of the Escherichia coli chromosome
      located between genes metE and udp and including the promoter region of the udp
      gene was determined. Multiple binding sites for the CytR and CRP proteins were
      identified outside the canonical udp gene promoter. A set of deletion variants
      with the truncated regulatory region of the udp gene was isolated based on
      plasmids pSKII and pJEL250. The level of CytR regulation of the udp gene was
      shown to depend on the size of the regulatory region relative to the
      transcription initiation site. On the basis of these data, it is concluded that
      additional binding sites for the CytR protein located in the regulatory region
      are functionally active in the regulation of udp gene expression. This conclusion
      has been confirmed by properties of the udp264 promoter mutant, which contains a
      deletion covering the main CytR binding site within the canonical promoter.
      Irrespective of the deletion, the expression of the udp gene in mutant udpP264
      retains the dependence on the allelic state of the cytR gene. The CytR protein
      was shown to act as a transcription repressor or activator, depending on the
      configuration of the promoter and on the relative location and quantity of
      binding sites for CytR and CRP proteins.

PMID- 9777354
TI  - [High-resolution GTG-banding and nucleolar organizer regions of chromosomes of
      two vole species: Microtus rossiaemeridonionalis and M. transcaspicus (Rodentia,
      Arvicolidae)].
AB  - With the use of the GTG-banding of prometaphase chromosomes, 503 and 402 segments
      were revealed in haploid chromosome sets of voles Microtus rossiaemeridionalis
      and M. transcaspicus, respectively. Based on a detailed study of chromosomes at
      different condensation levels, idiograms of M. rossiaemeridionalis and M.
      transcaspicus chromosomes were constructed. Sequential Ag-staining and GTG
      banding allowed nucleolar organizer regions (NORs) to be localized in 16 and 11
      chromosome pairs of M. rossiaemeridionalis and M. transcaspicus, respectively.

PMID- 9777355
TI  - [Cloning and analysis of DNA from interband regions 85D9/D10 and 86B4/B6 of
      Drosophila melanogaster polytene chromosomes].
AB  - A recently developed complex approach based on electron microscopic mapping of
      the P element inserts in the interband regions of Drosophila polytene chromosomes
      was used for the cloning and sequencing of DNA from the 85D9/D10 and 86B4/B6
      interband regions. The in situ hybridization technique showed that these DNA
      fragments belonged to the fraction of unique sequences of the Drosophila genome.
      Comparison of the cloned sequences with the earlier cloned 61C7/C8 interband
      region was carried out. Our findings indicated that these clones were represented
      by AT-rich sequences (over 80% AT) interspersed with segments with a random
      nucleotide composition. The interband regions were shown to contain large amounts
      of polypurine, polypyrimidine and purine-pyrimidine stretches. This structural
      organization is typical of DNA sequences that are able to form noncanonical
      secondary structures and is similar to that of matrix-attached DNA regions.
      Cloned interband DNA regions were shown to contain short open reading frames with
      an unknown functional activity.

PMID- 9777356
TI  - [Chromosome variation and anomalous karyotypes in the red-backed mouse
      Clethrionomys rufocanus (Rodentia, Microtinae)].
AB  - G-banding and C-banding of chromosomes were studied in populations of the red
      backed mouse Clethrionomys rufocanus from 11 localities of eastern Russia.
      Intrapopulation polymorphism of autosome 3 caused by the deletion-duplication of
      the short-arm heterochromatin (2n = 56; NFa = 56-58) was demonstrated. The
      karyotype of Cl. rufocanus from continental populations and Sakhalin Island was
      shown to have a large subtelocentric chromosome of pair 3 (NFa = 58), whereas in
      the population from Kunashir Island, chromosomes of this pair were acrocentric
      (NFa = 56). One animal from the population of the Kedrovaya Pad' Reserve
      (Primorsk krai) had a pericentric inversion (acrocentric morphology) of the Y
      chromosome. In two animals, a female from the Ussuriiskii Reserve (Primorsk krai)
      and a male captured near the Tomari Settlement (Sakhalin Island), a pericentric
      inversion of one chromosome of pair 6 was found (NFa = 59). The inversion
      detected in the animal from the Sakhalin population was accompanied by the loss
      of the centromeric heterochromatin. In contrast, the inversion of the chromosome
      pair 6, which was found in the mouse from the Primorsk krai population, did not
      involve the loss of centromeric heterochromatin. Analysis of our results and data
      from the literature showed that the karyotype of Cl. rufocanus is not constant,
      as was thought earlier. The percentage of animals with abnormal karyotype (1.6%)
      was higher than in other groups of red-backed mice studied (0.12-0.7%).

PMID- 9777357
TI  - [Distribution of family names in rural populations of Kursk region].
AB  - The coefficient of inbreeding and its components were calculated for populations
      of rural districts of Kursk oblast with the use of the isonymic method. The
      following values were obtained: F(it) = 0.000567, Fst = 0.000650, and Fis =
      0.000083. The Fst value agreed with the value of Malecot's local inbreeding
      coefficient (0.000201). In the districts where the proportions of families with
      frequent family names (FFNs; a frequency of 0.001 and more) were 50% and over,
      these family names were sufficient to adequately describe the population
      structure. The migration index and the index of family-name diversity were
      calculated. Significant correlations were revealed between Fst, the migration
      index, the index of family-name diversity, Malecot's local inbreeding, the mean
      square distance between birthplaces of spouses, the effective migration pressure,
      and the coefficient of linear systematic pressure.

PMID- 9777358
TI  - [Genetic-demographic processes in urban populations of the Ukraine in the 1990's.
      Marriage structure of the Kharkov population].
AB  - The characteristics of marriages contracted in 1993 in two districts of the city
      of Khar'kov were studied. The age, education, occupation, ethnicity, and
      birthplace of the spouses were recorded. The genetic demographic parameters of
      the marriage structure were compared to the results of a similar study performed
      in 1985. It was found that since 1985, the average age of marriage and the
      educational level of spouses had increased, while the ethnic diversity and
      coefficients of contingency by the spouses' ethnicity and profession had
      decreased. The contingency coefficient for the birthplace has increased. The
      causes and genetic consequences of these changes are discussed.

PMID- 9777359
TI  - [Frequency of the HLA-DP genes and the antigens of the HLA-A, -B, -Cw, and -DR
      loci in Tuvinians].
AB  - The results of DNA typing of the HLA-DPB1 gene among Tuvinians are described. The
      allele 0201 was found to be the most frequent (26.66%); then, in order of
      decreasing frequency, followed the alleles 0401 (26.42%), 0402 (13.99%), 0301
      (8.55%), 0501 (7.77%), 0901 (5.16%), and 1301 (2.07%). The frequency of the
      allele 0501 in Tuvinians was significantly lower than that in the published data
      on allele distributions characteristic of two other Mongoloid populations, the
      Manchu and Japanese. The results of the serological typing of the loci HLA-A, -B,
      and -Cw of class I in the Tuva population were compared to the corresponding
      published data on ten Mongoloid populations of Central and Eastern Asia: Uigurs,
      Kazakhs, Mongols, Manchu, Tibetans, the Chinese of the northern and southern
      regions of China, Thais (inhabitants of Northwestern Indochina), Koreans, and
      Japanese. In Tuvinians, the most frequent antigens were HLA-A2, -A9, -B0, -B35, 
      B17, -Cw4, and -DR5. In the inhabitants of Tuva, the frequency of the antigens
      HLA-A1, -A9, -B17, -Cw2, and -Cw4 was significantly higher than in other
      Mongoloids, while that of the antigens HLA-A26 and -B22 was lower. This
      difference was greatest in the case of antigen HLA-B40: it a frequency of 43.4%
      was detected in it, while in individuals of Mongolian origin, the frequency of
      this antigen did not exceed 22.5%. Indices of genetic similarity (IGSs),
      calculated from the gene frequencies of the loci HLA-A, -B, and -Cw, suggested
      that the Tuvinians were most closely related to Kazakhs (IGS = 0.73), and least
      related to the Japanese and Uigurs (IGS = 0.66). Our data suggest that Tuvinians
      significantly differ from the compared populations of Central and Eastern Asia.

PMID- 9777360
TI  - [Immunogenetic markers of erythrocyte systems in Armenians of Nagornii Karabakh].
AB  - Frequencies of antigens of erythrocytic systems Rh-Hr, MNSs, Pp, Kidd, Duffy,
      Kell-Chellano, and Lewis were studied in the indigenous Armenian population of
      Nagornyi Karabakh with regard to all possible genotypes. The results were
      compared with those obtained for populations of the Caucasus, Europe, and Asia.
      In general, the studied population had a typical Caucasoid gene system.

PMID- 9777361
TI  - [East European gene pool and diseases in the rural population of European
      Russia].
AB  - New data on the association of the state of health and the disease incidence with
      the gene pool were obtained in the East European population. The second principal
      component (PC2.G, 11.4% of the total variance) of the geographic variation in the
      gene pool (100 alleles of 34 loci) showed a distinct latitudinal dependence
      corresponding to the natural zonality of Eastern Europe. This was also
      characteristic of the first principal component (PC1.M, 75.6% of the total
      variance) of the geographic variation in the disease incidence (i.e., the number
      of all new cases diagnosed in out-patient clinics per year) in the rural
      population. The disease incidence decreased from the south-southeast to the north
      northwest in European Russia. The coefficient of the geographic pairwise
      correlation between PC2.G and PC1.M was r = 0.945; their specific correlation
      remained high (r = 0.864), even after a correction for the effects of age
      composition and heterozygosity. Thus, an insignificant variation in the gene pool
      was shown to significantly affect the geographic distribution of disease
      incidence in the East European population of Russia (eta 2 = 0.892). A
      correlation of mapped geographic distributions of PC1.M and PC2.G in the modern
      population with those of the principal components of the geographic variation of
      the late Paleolithic material culture in Eastern Europe was analyzed. The origin
      of the latitudinal zonality of the modern gene pool was dated back to the late
      Pleistocene-early Holocene. A conclusion was made that diseases that affected
      reproduction and lethality in the Paleolithic population still represent a
      mechanism of the gene pool's adaptation to the natural zonality of the
      environment. The latitudinal zonality of disease incidence, which was
      characteristic of the ancient population, is conserved in the today's population,
      owing to the gene pool.

PMID- 9777362
TI  - [A new inherited RET proto-oncogene mutation associated with familial medullary
      thyroid carcinoma and polymorphisms in adjacent regions].
AB  - A new point mutation, TCG(Ser)-->GCG(Ala) in codon 891, exon 15 of the RET
      protooncogene was revealed in two patients from a pedigree with familial
      medullary thyroid carcinoma (FMTC), but not in healthy persons. A linkage
      analysis with two well-known and two new intragene polymorphisms showed that
      informative polymorphic markers, the phenotypic expression of the disease, and
      the mutation are cosegregated in the studied pedigree. Two new polymorphisms, G/A
      at position-24 of intron 14 and C/T in codon 836 of exon 14, were found in the
      RET protooncogene. The frequencies of allele 1 of the polymorphic site in codon
      836 were the same (0.96) in the Russian and German populations. This was also
      characteristic of two polymorphisms revealed earlier, namely, the sites in codons
      691 (0.80 and 0.81, respectively) and 904 (0.21 and 0.22). However, the frequency
      of allele 1 of the polymorphisms in intron 14 differed significantly (0.87 and
      0.77, respectively).

PMID- 9777363
TI  - [Distribution of the 32 bp deletion in the CCR5 chemokine receptor gene in
      populations of the Volga-Ural region].
AB  - Data on the frequency of the CCR5 chemokine receptor-gene 32-bp deletion in seven
      Turkic (Bashkir, Tatar, and Chuvash) and Finno-Ugric (Mari, Komi, Mordvinian, and
      Udmurt) populations of the Volga-Ural region, obtained by means of the PCR
      technique, are presented. The deletion frequency varied from 2.17% in the
      northwestern ethnogeographic group of Bashkirs to 13.44% in the Tatar population,
      with a mean frequency value of 7.02% for the region. The only deletion homozygote
      found belonged to the Udmurt population. The results indicate that the frequency
      distribution of the mutant allele in Volga-Ural populations coincided with that
      in European populations.

PMID- 9777364
TI  - [The population-demographic structure and the prevalence of multifactorial
      diseases affecting the viability of the population of Kursk region].
AB  - A significant effect of the population structure on the incidence of
      multifactorial diseases affecting the viability of the adult population was found
      in rural districts of Kursk oblast. The diseases studied were chronic bronchitis,
      pulmonary emphysema, pneumosclerosis, and atherosclerosis. The incidence of
      multifactorial pathology increased with an increase in the homozygosity level of
      district populations. On average, the population structure affected the incidence
      of multifactorial diseases by 30-50%.

PMID- 9777365
TI  - [Evolutionary role of sex chromosomes (a new concept)].
AB  - Sex differentiation provides for testing evolutionary innovations in the male
      genome before they are transferred to the female genetic system. This is possible
      with dichronous (asynchronous) evolution, when evolution in males precedes that
      in females [3-7]. Hence, along with common autosomal genes for stable characters,
      exclusively male and exclusively female genes must exist. The male genes are
      already acquired by the male genome but are not yet transferred to the female
      one. The female genes are already lost by the male genome but still remain in the
      female genome. They constitute temporary evolutionary genotypic sexual
      dimorphism. Common genes cannot exhibit genotypic sexual dimorphism; they show
      only constant phenotypic hormonal sexual dimorphism. On the basis of the
      interpretation of genotypic sexual dimorphism as a consequence of sex dichronism,
      the evolutionary role of sex chromatins is clarified and a new concept for them
      is suggested. According to this concept, the Y chromosome is the "conductor" of
      ecological information into the genome, the "place of birth" and testing of new
      genes, the accelerator and regulator of genotypic sexual dimorphism. By contrast,
      the X chromosome of the heterogametic sex provides the transportation of new
      genes from the Y chromosome to autosomes. This chromosome stabilizes, relaxes,
      and suppresses genotypic sexual dimorphism and accumulates genes that will be
      eliminated. This concept sheds light on many problems: the chromosomal
      localization of genes and their transfer to other chromosomes, the inactivation
      of chromosomes, mobile genes, mutation bursts, insertional mutagenesis, the
      association of the Y chromosome with stress, retroviruses, etc. In particular, it
      explains why genes "jump," why transpositions of mobile elements depend on
      ecological stress, why different genes mutate simultaneously, etc.

PMID- 9777366
TI  - Evidence for upregulation and redistribution of vascular endothelial growth
      factor (VEGF) receptors flt-1 and flk-1 in the oxygen-injured rat retina.
AB  - There is considerable evidence that vascular endothelial growth factor (VEGF) is
      important in the pathogenesis of retinal neovascular diseases. The effects of
      this endothelial cell-specific mitogen are mediated by specific cell surface
      receptors. In this study we probed for the two VEGF receptors (VEGFRs) known to
      have highest affinity in the rat--flt-1 and flk-1. Using a well-characterized rat
      model of the neovascular disease retinopathy of prematurity (ROP), we performed
      immunohistochemical assays on methacrylate sections of eyes from normal and
      oxygen-injured animals at the time neovascularization is first observed (16 days
      of age) and at its peak (day 20). In day 16 room air retinas there was light,
      diffuse labeling of the inner nuclear layer and outer plexiform layer. In
      contrast, in 4 of 5 oxygen-injured eyes on day 16, there was specific labeling of
      small neovascular growths and normal retinal vessels, and the outermost (sclerad)
      limit of the label had shifted inward to the vitread border of the inner nuclear
      layer and the inner plexiform layer. Day 20 room air eyes showed a pattern
      similar to day 16, although with stronger labeling. However, in oxygen-injured
      eyes on day 20 the labeling pattern had shifted toward the vitreous, with
      extremely strong labeling of the preretinal neovascular growths. As on day 16
      there was also labeling of the inner plexiform layer and the inner portion of the
      inner nuclear layer, but not the outer plexiform layer. Comparison of VEGF
      protein immunolabel with both of the VEGFR immunolabels revealed overlap and
      strong similarity on day 20 in the oxygen-injured eyes. This is the first report
      of VEGF receptor protein being concentrated in preretinal neovascular growths in
      a model of ROP. These results lend themselves to further investigation of the
      roles of VEGFRs in preretinal neovascularization in ROP and other retinal
      diseases and suggest avenues of research toward therapies using VEGFR
      antagonists.

PMID- 9777367
TI  - Ovine vascular endothelial growth factor: nucleotide sequence and expression in
      fetal tissues.
AB  - To examine the role of vascular endothelial growth factor (VEGF) in mediating
      angiogenesis and vascular permeability during fetal development, we determined
      the gene expression of VEGF in ovine fetal tissues. Further, we cloned and
      sequenced the ovine VEGF cDNA encoding VEGF164 from sheep placenta. VEGF protein
      was localized in epithelial cells of the placenta and fetal kidney, and in
      hepatocytes of the fetal liver. By Northern analysis, a major VEGF mRNA species
      of 3.7 kb was identified in all tissues examined, with abundance highest in the
      lung and lowest in the liver. The most prominent molecular form expressed in
      ovine fetal tissues appeared to be VEGF164 with low levels of expression of
      VEGF120 and VEGF188. Cloning and sequence analysis of the most abundant form of
      ovine VEGF cDNA in the placenta confirmed the prediction of a 164-amino acid
      peptide, with a putative N-terminal signal sequence of 26 amino acids. Comparison
      of the VEGF cDNA sequence among different species revealed that VEGF is highly
      conserved suggesting an important role in development.

PMID- 9777368
TI  - RGTA11, a new healing agent, triggers developmental events during healing of
      craniotomy defects in adult rats.
AB  - RGTA are chemically defined compounds which proved to be very potent healing
      agents in various tissue repair models including skin, muscle and nerve. These
      chemicals are believed to protect endogenously released heparin-binding growth
      factors and enhance their bioavailability during healing. In craniotomy defects
      that do not heal spontaneously in adults, RGTA promoted dose-dependent skull
      closure. The aim of this work was to characterize, in the same model, the events
      associated with wound closure by studying the expression of the osteoblastic
      phenotype and the distribution of some matrix proteins during RGTA11-induced bone
      healing. Craniotomy defects in rats were implanted with collagen plasters soaked
      in a solution of RGTA11 (1.5 micrograms per piece). The skulls were removed 30
      days after wounding, a stage of almost complete bone filling in treated samples.
      Bone formed only at the edges of the defect in controls, while it formed also at
      the center in the form of nodules in the treated samples. RGTA11 modified the
      amount and distribution of the tissues including bone in the wounds. In some
      RGTA11-treated samples, skull closure by bone occurred and the median suture was
      restored. In the treated defects, alkaline phosphatase-positive (osteoprogenitor)
      cells were far more numerous and were distributed differently. Type I and III
      collagen and fibronectin deposition was markedly enhanced in the bone compartment
      of the wounds. Secretory osteoblasts released type III collagen. Osteocalcin
      expression was enhanced by RGTA11. RGTA11 thus modified the healing pattern by
      increasing both the cellularity and the synthesis of a bone-competent
      extracellular matrix, thereby restoring the original anatomy of the skull. Flat
      bone regeneration can be triggered in adults through developmental events (i.e.
      nodule formation, secretion of type III collagen by osteoblasts, suture
      restoration...) that are no longer operative in the wounds of mature individuals.

PMID- 9777369
TI  - Biomolecular interaction analysis of IFN gamma-induced signaling events in whole
      cell lysates: prevalence of latent STAT1 in high-molecular weight complexes.
AB  - The basic framework for the JAK/STAT pathway is well documented. Recruitment of
      latent cytoplasmic STAT transcription factors to tyrosine phosphorylated docking
      sites on cytokine receptors and their JAK-mediated phosphorylation instigates
      their translocation to the nucleus and their ability to bind DNA. The biochemical
      processes underlying recruitment and activation of this pathway have commonly
      been studied in reconstituted in vitro systems using previously defined
      recombinant signaling components. We have dissected the Interferon gamma (IFN
      gamma) signal transduction pathway in crude extracts from wild-type and STAT1
      negative mutant cell lines by real-time BIAcore analysis, size-exclusion (SE)
      chromatography and immuno-detection. The data indicate that in detergent-free
      cell extracts: (1) the phospho-tyrosine (Y440P)-containing peptide motif of the
      IFN gamma-receptor alpha-chain interacts directly with STAT1, or STAT1 complexes,
      and no other protein; (2) non-activated STAT1 is present in a higher molecular
      weight complex(es) and, at least for IFN gamma-primed cells, is available for
      recruitment to the activated IFN gamma-receptor from only a subset of such
      complexes; (3) activated STAT1 is released from the receptor as a monomer.

PMID- 9777370
TI  - Biochemical characterization of mutant EGF receptors expressed in the hemopoietic
      cell line BaF/3.
AB  - The Epidermal Growth Factor (EGF) receptor appears to require a fully active
      tyrosine kinase domain to transmit mitogenic signals. However, waved-2 mice
      carrying a mutation in the alpha-helix C of their EGF-R, which abolishes tyrosine
      kinase activity, only display a mild phenotype and are fully viable. This
      suggests that the mutant EGF-R signals through heterodimerization with
      endogenous, kinase active members of the EGF-R family such as ErbB-2 or ErbB-4.
      We have examined the biochemistry of EGF-Rs carrying mutations in the alpha-helix
      C of the human EGF-R (V741G and Y740F), in the ATP binding site (K721R) and at
      the C-terminus (CT957), by expression in BaF/3 cells which are devoid of EGF-R
      family members. The in vitro kinase activity of the alpha-helix C EGF-R mutants
      was severely impaired as a result of reduced phosphotransfer activity without
      appreciable changes in the affinity for either ATP or peptide substrate.
      Surprisingly, EGF stimulation of cells carrying the different mutant or wild type
      EGF-Rs resulted in tyrosine phosphorylation of EGF-R proteins; this
      phosphorylation was abolished in crude plasma membrane preparations, and appears
      to be due to activation of a membrane-associated or a cytosolic kinase. Receptor
      mediated internalization of EGF was profoundly suppressed in the V741G, K721R and
      CT957 receptor mutant, and high affinity EGF binding was undetectable in the
      V741G and K721R receptors. We conclude that specific residues in the C-helix of
      the EGF-R kinase are essential for full kinase activity; mutations in this region
      do not affect ATP binding, but impair the receptors' phosphotransfer ability.
      High affinity binding of EGF is not dependent on tyrosine kinase activity or
      sequences in the C-terminus.

PMID- 9777371
TI  - Androgen regulation of prostate cancer cell FGF-1, FGF-2, and FGF-8: preferential
      down-regulation of FGF-2 transcripts.
AB  - Using quantitative RT-PCR, we found that T1 rat prostate cancer cell relative FGF
      1 transcript content was about 180-fold greater than that of FGF-2. This
      difference in transcript content was not representative of T1 cell relative FGF-1
      and FGF-2 protein content which showed, at most, only a 4- to 5-fold greater FGF
      1 content. Testosterone caused time-dependent down-regulation of prostate cancer
      cell FGF-2 transcript content without influencing either FGF-1 or FGF-8
      transcript content or T1 cell proliferation. Moreover, testosterone-mediated down
      regulation of prostate cancer cell FGF-2 transcripts did not result in a
      statistically significant change in 21.5 or 17.0 kD FGF-2 isoform content. By
      contrast, an approximately 20% statistically significant decrement in 19.5 kD FGF
      2 isoform content was demonstrable following 24 h testosterone treatment.
      However, following 72 h testosterone treatment, T1 cell 19.5 kD FGF-2 isoform
      content was not statistically significantly different from that of control. It is
      probable that the modest and variable decrement in 19.5 kD isoform content is not
      physiologically significant and is attributable to artifact resulting from
      difficulty quantifying this minor component of the FGF-2 isoforms. Transient
      transfection analysis showed that androgen caused concentration-dependent
      increases in MMTV-LTR regulated expression of chloramphenicol acetyl transferase
      activity. Consequently, the failure of androgen to affect either T1 cell FGF-1
      and FGF-8 transcript content or T1 cell proliferation could not be attributed to
      defective androgen receptor function. Moreover, the absence of a close
      relationship between T1 cell FGF-2 transcript and FGF-2 protein content implies
      that FGF-2 transcript content is not the dominant determinant of prostate cancer
      cell FGF-2 protein content. Testosterone-mediated down-regulation of prostate
      cancer-cell gene expression may have significance for clinical management of
      human disease that is treated by androgen ablation. The possibility that such
      ablation may enhance aggressiveness of "androgen-independent" cells by selective
      upregulation of gene expression merits further consideration.

PMID- 9777372
TI  - Cardiac surgery and the acute care nurse practitioner--"the perfect link".

PMID- 9777373
TI  - Measurement of glucose in tracheobronchial secretions to detect aspiration of
      enteral feedings.
AB  - OBJECTIVES: To determine (1) the relationship between results from 2 methods to
      measure glucose in tracheobronchial aspirates, (2) the effect of blood glucose
      levels on tracheobronchial glucose levels, and (3) the relationship between
      results from 2 methods to measure glucose in selected enteral formulas. DESIGN:
      Descriptive. SETTING: Two midwestern acute-care hospitals, a research laboratory,
      and a clinical laboratory. PATIENTS: Sixty-two acutely ill adult subjects with
      artificial airways whose secretions required frequent suctioning for therapeutic
      purposes; 53 of these 62 patients also required capillary blood glucose
      measurements for therapeutic purposes. OUTCOME MEASURES: Glucose concentrations
      in tracheobronchial secretions, capillary blood, and selected enteral formulas.
      INTERVENTION: None. RESULTS: Measures of glucose content made on 75 split samples
      of tracheobronchial secretions by 2 methods (glucose oxidase reagent strips and a
      laboratory assay) were highly correlated (ri = 0.94; P < .001) and mean readings
      were not statistically different (P = .17). Sixty-six capillary blood glucose
      readings made within 5 minutes of tracheobronchal suctioning correlated poorly
      with the glucose content in the tracheobronchial aspirates (r = 0.12; P = .36).
      Glucose concentrations in 22 enteral formulas determined by 2 methods correlated
      highly (r = 0.95; P < .001). Glucose concentrations were higher with the
      laboratory assay (259.6 +/- 206.3 mg/dL) than with glucose oxidase reagent strips
      (188.6 +/- 157.5 mg/dL). CONCLUSION: It appears appropriate to use glucose
      oxidase reagent strips to estimate glucose concentrations in tracheobronchial
      fluid. Elevated blood glucose levels apparently do not have a major effect on the
      glucose content in tracheobronchial fluid. Although mean glucose concentrations
      in the 22 formulas were higher with the laboratory assay, the readings were
      sufficiently similar to allow using glucose oxidase reagent strips to give a good
      estimation of the formulas' glucose content.

PMID- 9777374
TI  - Pulmonary thromboendarterectomy: an advance in the treatment of chronic
      thromboembolic pulmonary hypertension.
AB  - A new surgical procedure, pulmonary thromboendarterectomy, provides innovation in
      the surgical management of chronic thromboembolic pulmonary hypertension. This
      article will provide an overview of the surgical procedure itself as well as
      preindications for surgery and postoperative management. A clinical case study of
      a patient who has experienced the surgical procedure will be shared to apply the
      care management techniques outlined in the article.

PMID- 9777376
TI  - Perceived side effects and benefits of coronary angioplasty in the early recovery
      period.
AB  - OBJECTIVE: To examine patients' perceptions of the side effects and the treatment
      benefit of percutaneous transluminal coronary angioplasty (PTCA) in the early
      postdischarge recovery period, and to determine whether selected demographic and
      clinical variables were associated with perceptions of side effects and treatment
      benefit. DESIGN: Descriptive, correlational study. SAMPLE: Convenience sample of
      62 subjects, with a mean age of 62 years (SD 11 years), 77% of whom were men, who
      had undergone successful, elective PTCA. RESULTS: Fifty-two percent of subjects
      reported side effects 2 weeks after PTCA. The most frequently reported side
      effect (22.5%), was discomfort in the groin site. Seventy-nine percent of
      subjects reported PTCA made things better, and 5% reported that PTCA made things
      worse. The most commonly reported benefit of PTCA was relief of chest pain. Age,
      sex, and a history of previous PTCA were not related to reported side effects or
      reported benefits. Subjects who experienced chest pain since the time of hospital
      discharge were less likely to report that PTCA was beneficial. CONCLUSION: More
      emphasis should be placed on helping patients who are candidates for a PTCA to
      predict and to manage treatment side effects and to have realistic expectations
      concerning the trajectory of recovery from PTCA. Further research is needed to
      examine the impact of patients' uncertainty concerning treatment benefit or
      perceptions of no treatment benefit in the early recovery period on intermediate
      and long-term PTCA recovery outcomes.

PMID- 9777375
TI  - Pulmonary manifestations of inhaled street drugs.

PMID- 9777378
TI  - Development of the Sternal Wound Infection Prediction Scale.
AB  - OBJECTIVE: To develop an instrument to reliably predict the occurrence of sternal
      wound infection (SWI). DESIGN: Instrument development with retrospective chart
      review. SETTING: Southwestern university-affiliated medical center. PATIENTS: One
      hundred eighty-five adults who underwent cardiac surgery. SWI developed in 94
      patients, and 91 remained infection free. In phase 1, there were 82 subjects: SWI
      developed in 41, and 41 remained infection free. In phase 2, there were 103
      subjects: SWI developed in 53, and 50 remained infection free. OUTCOME MEASURE:
      Development of a postoperative SWI. INTERVENTION: The Sternal Wound Infection
      Prediction Scale (SWIPS) was developed in 2 phases. Phase 1 consisted of
      designing the SWIPS with use of 19 risk factors most often identified with SWI
      and revising this scale (SWIPS-R) with use of 21 risk factors. Eighty-two patient
      records were reviewed. After determining the mean cutscores in phase 1, phase 2
      provided cross-validation results with use of 103 additional patient records.
      RESULTS: The SWIPS produced 62.1% correct predictions of infection and
      noninfection; whereas the SWIPS-R produced 72.8% correct predictions. Phase 2
      cross-validation results for the 21 risk factors demonstrated that 62.1% and
      72.8% of the patients were correctly diagnosed using the SWIPS and SWIPS-R,
      respectively. A multivariate logistic regression was also performed on the risk
      factors to predict infection/noninfection groups for all 185 patients. A reduced
      logistic regression model included 9 of the risk factors and correctly classified
      76.2% of the subjects. CONCLUSIONS: The SWIPS-R, with 21 risk factors, and the
      logistic regression model, with 12 risk factors, provided excellent
      classification rates of infection/noninfection. However, more data need to be
      collected to further strengthen reliability.

PMID- 9777377
TI  - Symptom experience associated with maintenance immunosuppression after heart
      transplantation: patients' appraisal of side effects.
AB  - OBJECTIVE: To evaluate symptom experience related to side effects of
      immunosuppressive therapy in heart transplant recipients. METHODS: This
      descriptive, cross-sectional study included 105 heart transplant recipients (90
      men; 15 women) with a median age of 56 years. Maintenance immunosuppression
      consisted of triple therapy (cyclosporine, corticosteroids, azathioprine).
      Symptom frequency and symptom distress were assessed by an adapted version of the
      Transplant Symptom Frequency and Symptom Distress Scale, which includes 27
      symptoms associated with side effects of immunosuppressive therapy. RESULTS: The
      most frequent symptom for both sexes was increased hair growth. Impotence and
      painful menstruation were experienced as the most distressing symptoms for men
      and women, respectively. Women reported a significantly higher level of symptom
      experience. The majority of the most frequent and most distressing symptoms were
      corticosteroid associated. CONCLUSIONS: Patients' perception of side effects
      completes the symptomatologic profile of immunosuppressive therapy. A gender
      specific evaluation is indicated because symptom experience differs between the
      sexes.

PMID- 9777379
TI  - Factors influencing intensive care unit survival for critically ill elderly
      patients.
AB  - OBJECTIVE: To examine factors influencing intensive care unit (ICU) survival for
      critically ill elderly patients and to compare survivors and nonsurvivors of ICU
      on demographic and illness-related variables. DESIGN: Retrospective, ex post
      facto research design. SETTING: Adult medical and surgical ICUs. PATIENTS: The
      records of 164 survivors and 111 nonsurvivors from 2 medical-surgical ICUs were
      examined. Patients were placed into 3 age groups (middle-aged, young-old, and old
      old) to compare outcomes for elderly ICU patients. OUTCOME MEASURES: ICU
      survival, ICU treatments received, severity of illness. INTERVENTION: The Acute
      Physiology Age and Chronic Health Evaluation II (APACHE II) was used to assess
      illness severity. Additional illness-related information was collected by chart
      review. RESULTS: Predictors of ICU nonsurvival were severity of illness (measured
      by APACHE II scores) and intubation. Comparison of survivors and nonsurvivors
      revealed no statistically significant differences in sex or age. For all age
      groups, nonsurvivors had significantly higher mean days of ICU hospitalization (F
      (1,239) = 7.20 P < .0078) and higher APACHE II scores (F (1,239) = 106.5 P <
      .0001). Analysis of ICU treatments received by the 3 age groups of survivors
      revealed a significant difference only on oxygen therapy, (chi-square = 10.2, df
      = 2, P = .006), with more young-old (aged 65 to 79) and old-old (aged 80 and
      older) ICU patients receiving oxygen therapy than middle-aged patients (aged 45
      to 64). CONCLUSIONS: The findings of this study demonstrated that severity of
      illness was a predictor of ICU outcome; age was not. Additionally, age was not
      related to ICU treatments received.

PMID- 9777380
TI  - Schwannoma of posterior mediastinum: a case report and concise review.
AB  - In the vast majority of cases, schwannoma (neurilemmoma) of the posterior
      mediastinum arises from 1 of the intercostal nerves and most often is manifested
      by an asymptomatic solitary mass on a radiograph. This case report emphasizes the
      importance of new imaging studies in the diagnosis of this classic tumor of the
      mediastinum, with special regard to the differential diagnosis of such a tumor.

PMID- 9777381
TI  - Pseudosepsis secondary to bilateral adrenal hemorrhage.

PMID- 9777382
TI  - Dominant R wave in lead V1.

PMID- 9777383
TI  - Continuous positive airway pressure: patients' and caregivers' learning needs and
      barriers to use.

PMID- 9777384
TI  - Problems arising from eastern and western classification systems for
      gastrointestinal dysplasia and carcinoma: are they resolvable?
AB  - It has become increasingly apparent that the Japanese and Western systems of
      classifying dysplasia and carcinoma in the gastrointestinal tract are not the
      same. The implication of these differences is that in an article in a Western
      journal on gastrointestinal 'cancer' originating from Japan, it is often
      impossible to repeat the study to confirm or refute it, because of these
      differences in definitions. Although there is no reason why it should not be just
      as much of a problem if Western research is published in Japanese journals, this
      is currently not a major problem. The terminological differences do not mean that
      one is right and one wrong; they are simply different. We had an opportunity to
      look at these differences in detail in a series of 100 gastric biopsies. In this
      review, we outline these differences and indicate the similarities, differences
      and problems between these two systems. 'Carcinoma' is diagnosed in Japan by
      virtue of its structural and cytological features, but by invasion in the Western
      system. Adenoma does not mean a dysplastic lesion in the Japanese system
      (although it can) but in most cases is similar to low-grade dysplasia
      irrespective of the macroscopic/endoscopic appearances (hence flat and depressed
      adenomas in the Japanese system); however, most examples of high-grade dysplasia
      in the Western system, as well as some low-grade dysplasia, becomes 'cancer' in
      the Japanese system. Conversely, both have conceptual areas that are useful in
      the other's systems. Because we were ultimately able to use each other's systems,
      we were able to show where these systems come together and diverge. These provide
      hope that a common classification encompassing both systems that allows
      communication between both systems is feasible.

PMID- 9777385
TI  - The value of classifying interstitial pneumonitis in childhood according to
      defined histological patterns.
AB  - AIMS: Interstitial pneumonitis in children is very rare and most cases have been
      classified according to their counterparts in adults, although the term 'chronic
      pneumonitis of infancy' has recently been proposed for a particular pattern of
      interstitial lung disease in infants. We reviewed our paediatric cases of
      interstitial pneumonitis, first, to look at the spectrum of histological patterns
      found in this age group and, second, to determine whether the classification of
      such cases in childhood is both appropriate and worthwhile. METHODS AND RESULTS:
      Twenty-five of 38 open lung biopsies showed an overlapping spectrum of
      interstitial pneumonitis, including three cases that fulfilled the histological
      criteria for chronic pneumonitis of infancy. There were 11 cases of reactive
      pulmonary lymphoid hyperplasia (either lymphoid interstitial pneumonitis or
      follicular bronchiolitis), five of which were associated with abnormalities of
      the immune system. Four cases were classified as desquamative interstitial
      pneumonitis and the remaining seven cases were classified as nonspecific
      interstitial pneumonitis. There were no cases with the histological features of
      usual interstitial pneumonitis. Most patients responded to steroids but tended to
      have a residual deficit in lung function. Mortality appeared to be associated
      with presentation at a young age. CONCLUSION: Classification of interstitial
      pneumonitis according to their adult counterparts is appropriate for this younger
      age group and can provide valuable information for the clinician. The term
      'chronic pneumonitis of infancy' refers to a specific histological pattern, but
      whether it represents a separate disease or a reflection of pulmonary immaturity
      remains to be proven.

PMID- 9777386
TI  - Xanthogranulomatous cystitis associated with malignant neoplasms of the bladder.
AB  - AIMS: Two cases of xanthogranulomatous cystitis in conjunction with malignant
      neoplasms of the bladder are described. METHODS AND RESULTS: A partial cystectomy
      [corrected] specimen from a 55-year-old man showed a urachal adenocarcinoma
      partly surrounded by a large xanthogranulomatous inflammatory mass. Multiple
      resections of the locally recurring tumour over the subsequent 10 years did not
      show further xanthogranulomatous changes. In the second case, a 76-year-old
      woman, a focus of xanthogranulomatous cystitis was present near a moderately
      differentiated transitional-cell carcinoma of the vesico-ureteric junction.
      CONCLUSIONS: Xanthogranulomatous inflammation is associated with malignant
      neoplasms in the bladder as it is in the kidney and extra-urinary sites, as well
      as with benign neoplasms and non-neoplastic conditions such as urachal
      diverticula. The presence of a concomitant neoplasm should therefore be
      considered when the diagnosis of xanthogranulomatous cystitis is made.

PMID- 9777387
TI  - Epithelioid cell granulomas in chronic hepatitis C: immunohistochemical character
      and histological marker of favourable response to interferon-alpha therapy.
AB  - AIMS: The clinicopathological significance of intrahepatic epithelioid cell
      granulomas in chronic hepatitis C was determined. METHOD AND RESULTS:
      Granulomatous lesions were surveyed in 542 liver biopsy specimens and were
      immunohistochemically examined. We also tested whether this lesion is a marker of
      response to interferon-alpha therapy in chronic hepatitis C. Granulomatous
      lesions in hepatic lobules and/or portal tracts were identified in 11/542 (2%)
      cases with chronic hepatitis C. Granulomas were positive for HLA-DR and beta 2
      microglobulin, and were surrounded by T-cells. Among them, three chronic
      hepatitis C cases showed portal granulomas with mild biliary epithelial damage.
      Bile ducts showing mild epithelial damage in chronic hepatitis C were positive
      for beta 2-microglobulin, but negative for HLA-DR, while both antigens were
      frequently expressed in damaged bile ducts in primary biliary cirrhosis (PBC).
      All five cases of chronic hepatitis C with granulomas who had interferon-alpha
      therapy and were followed up and were found to have responded well. CONCLUSION:
      Granulomas showed the same immunohistochemical phenotypes, though the expression
      of HLA-DR on bile ducts in PBC but not in chronic hepatitis C suggests a
      different pathogenesis. Granulomas may predict a favourable response to
      interferon-alpha therapy in chronic hepatitis C.

PMID- 9777388
TI  - HIV-associated lymphoepithelial cysts and lesions: morphological and
      immunohistochemical study of the lymphoid cells.
AB  - AIMS: To determine the morphology, immunophenotype and bcl-2 protein status of
      intraepithelial lymphocytes in HIV-positive lymphoepithelial lesions. METHODS AND
      RESULTS: Seventeen cases (from adults and children) of HIV-associated parotid and
      lung lymphoid lesions were examined. In addition, three lymphoepithelial cysts
      from HIV-negative patients were studied in parallel. Immunohistochemistry was
      performed on paraffin embedded tissue with the following antibodies: CD20, CD79a,
      CD3, CD4, CD8, bcl-2, CAM5.2, AE1/3, MIB1, kappa/lambda light chains and EBV-LMP
      1. Heavy chain rearrangement was sought by polymerase chain reaction (PCR) in
      four of the cases. The lymphocytes participating in lymphoepithelial lesions of
      HIV-positive patients had the morphology of centrocyte-like cells with occasional
      cells resembling centroblasts. The majority of these cells were of B-cell
      lineage, but occasional intraepithelial T-cells (CD8 positive, CD4 negative) were
      also present. T-cells also formed a significant component of the infiltrative
      lymphoid cells outside the lymphoepithelial lesions. These were mainly CD8
      positive, but very occasional CD4-positive T-cells were also noted. None of the
      cases showed light chain restriction and the four cases did not demonstrate heavy
      chain rearrangement by molecular biology. The interesting finding was the absence
      of bcl-2 expression by the intraepithelial lymphocytes. In contrast, the
      intraepithelial lymphocytes seen in the non-HIV setting were strongly bcl-2
      positive. The majority of these were B-cells, and very occasional CD8 and CD4
      positive T-cells formed the intraepithelial population. CONCLUSION: It is
      postulated that this finding is due to the HIV causing down-regulation of bcl-2
      protein.

PMID- 9777389
TI  - A marginal zone pattern may be found in different varieties of non-Hodgkin's
      lymphoma: the morphology and immunohistology of splenic involvement by B-cell
      lymphomas simulating splenic marginal zone lymphoma.
AB  - AIMS: Splenic marginal zone lymphoma (SMZL) is characterized by a micronodular
      infiltrate of the splenic white pulp, centred on pre-existing follicles, with a
      peripheral rim of 'marginal' zone B-cells, always accompanied by a variable
      degree of red pulp infiltration. These histological features can be closely
      mimicked by a variety of other small B-cell lymphomas when they involve the
      spleen, which makes recognition of SMZL difficult. We therefore have compared the
      histopathological and immunohistochemical features of other non-Hodgkin's
      lymphoma (NHL) types with those of SMZL. METHODS AND RESULTS: We selected cases
      of splenic involvement by different types of B-cell lymphoma, including mantle
      cell lymphoma (MCL), follicular lymphoma (FL), immunocytoma (IM) and lymphocytic
      lymphoma (B-CLL). A micronodular pattern and marginal zone differentiation were
      both found to be frequently present in FL and MCL, and with lesser frequency in
      IM and B-CLL. The main morphological feature useful for differential diagnosis
      was the cytological composition of the white pulp tumoral nodules. SMZL is
      distinguished by characteristic dimorphic cytology, different from the
      monomorphic cytology of MCL, and the distinctive mixture of centroblasts and
      centrocytes which is the rule in FL. B-CLL could also be identified on the basis
      of the polymorphic cytology including small lymphocytes and prolymphocytes,
      whereas cases diagnosed as IM show prominent plasmacytic differentiation, lacking
      the features of the other lymphoma types. Immunohistochemistry was particularly
      useful for the differential diagnosis. Thus the recognition of MCL was
      facilitated by the identification of cyclin D1 and CD43 reactivity, while FL
      could be recognized by the lack of IgD expression or the distinctive pattern of
      Ki67 staining found in SMZL. B-CLL cells were CD23+, CD43+. CONCLUSION: The
      results of this study provide morphological and immunohistological information
      useful in the recognition of the different varieties of NHLs when involving the
      spleen and the differential diagnosis of SMZL.

PMID- 9777391
TI  - Histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease): continuing
      diagnostic difficulties.
AB  - AIMS: To describe the clinicopathological and immunophenotypic features of 25
      cases of Kikuchi-Fujimoto disease (K-F), which remains a poorly recognized entity
      and is still frequently confused with malignant lymphoma, and to discuss the main
      diagnostic problems experienced by the referring pathologist. METHODS AND
      RESULTS: Haematoxylin and eosin sections of 27 lymph node biopsies were re
      examined. Immunostains for B-lymphocytes, T-lymphocytes and macrophages were
      performed. Clinical and follow-up data were obtained through a questionnaire to
      the referring pathologist or from the patients' notes where available. The
      suggested initial diagnoses are discussed. The lymph nodes showed a necrotizing
      process characterized by patchy or confluent areas of necrosis associated with
      karyorrhexis and absence or paucity of granulocytes. This was associated with a
      proliferation of large blastic cells consisting of a mixture of T-lymphocytes and
      histiocytes. Fragmentation of the biopsy was a frequent feature. The diagnosis of
      K-F was suggested by the referring pathologist in three cases only. The most
      common suggested diagnosis was that of a non-Hodgkin's lymphoma. CONCLUSION: This
      series documents continuing difficulties in the diagnosis of Kikuchi-Fujimoto
      disease in the UK and emphasizes that cases are still being mistakenly diagnosed
      as malignant lymphomas. The diagnosis of Kikuchi-Fujimoto disease merits active
      consideration in any nodal biopsy showing fragmentation, necrosis and
      karyorrhexis, especially in young women presenting with cervical lymphadenopathy.

PMID- 9777390
TI  - Prognostic relevance of apoptotic cell death in non-Hodgkin's lymphomas: a
      multivariate survival analysis including Ki67 and p53 oncoprotein expression.
AB  - AIMS: To evaluate the independent prognostic value of apoptotic versus
      proliferative fractions in a series of 92 patients with non-Hodgkin's lymphomas
      (NHL). METHODS AND RESULTS: Apoptotic fractions were quantified by use of the TdT
      (terminal deoxynucleotidyl-transferase)-mediated in-situ end-labelling technique
      (TUNEL), the percentage of positive cells constituting the apoptotic index (AI).
      Proliferative rate was expressed as percentage of Ki67 positive cells (Ki67 LI).
      Tissues were also stained for p53 protein with the DO-1 antibody. Patients were
      followed up until death (n = 33) or for an average of 63 months (n = 56). AI
      increased with malignancy grade and proliferative activity but was not related to
      location, cell of origin, clinical stage, bone marrow involvement and p53
      expression. In multivariate analysis, overall survival was independently
      influenced by grade, stage, p53 LI and chemotherapy. The independent predictors
      of disease-free survival were Ki67 LI location and chemotherapy. AI turned out to
      be the only independent (negative) predictor of post-relapse survival. On the
      other hand, a low Ki67 LI increased the risk of relapse (logistic regression
      analysis) whereas a low p53 LI increased the probability of complete response.
      CONCLUSIONS: Our results suggest that the combined assessment of apoptotic
      fraction, proliferative rate and p53 expression may provide important prognostic
      information independent of other clinicopathological parameters in NHL.

PMID- 9777393
TI  - Loss of basement membrane components laminin and type IV collagen parallels the
      progression of oral epithelial neoplasia.
AB  - AIMS: To determine the immunohistochemical localization of basement membrane
      components laminin and type IV collagen in premalignant and malignant lesions of
      the oral epithelium. METHODS AND RESULTS: Formalin-fixed tissue sections of 12
      epithelial hyperplasias with no dysplasia and 30 dysplasias, clinically diagnosed
      as leukoplakia and/or erythroplakia, as well as 50 invasive squamous cell
      carcinomas, were stained with mouse monoclonal antibodies to human laminin and
      type IV collagen. Statistical analysis showed that there was a linear trend for
      discontinuous distribution of laminin from epithelial hyperplasia to epithelial
      dysplasia and invasive squamous cell carcinoma (P < 0.001). Laminin staining
      showed a linear trend for discontinuity with increasing grade of dysplasia (P <
      0.05) and was more frequently discontinuous in areas of deep tumour invasion than
      in central or superficial areas (P < 0.05). Brush-shaped thickening and
      reduplication of the basement membrane were also identified. CONCLUSIONS:
      Alterations in the distribution of laminin and type IV collagen in oral
      premalignant and malignant lesions indicate that the loss of continuity of the
      subepithelial basement membrane parallels the progression of the neoplastic
      transformation process in oral epithelium.

PMID- 9777392
TI  - Diagnostic lessons of mucosal melanoma with osteocartilaginous differentiation.
AB  - AIMS: To document the clinical, morphological and immunohistochemical features of
      two cases of primary mucosal melanoma with osteocartilaginous differentiation.
      MATERIALS AND METHODS: Two cases of mucosal melanoma with cartilage and bone
      formation are reported, one arising in the vagina of a 79-year-old woman and one
      in the oral cavity of a 67-year-old man. The vaginal melanoma exhibited only
      cartilaginous differentiation. The oral cavity mucosal melanoma exhibited both
      bone and cartilage formation and was remarkable for its multifocality, long
      history not associated with metastases and its lengthy manifestation of dual
      morphologies: some of the tumours were typical in situ/invasive melanotic
      melanomas whilst the others were composed of amelanotic spindle and epithelioid
      cells with osteocartilaginous tissue. One of the lesions exhibited in situ and
      invasive melanoma with transition to an osteogenic tumour in places. The patient
      also developed nonosteogenic malignant melanomas in the nasal cavity and
      nasopharynx. CONCLUSIONS: Malignant melanomas showing foci of osteocartilaginous
      differentiation are extremely rare with only 18 cases reported. Primary mucosal
      malignant melanomas of vagina and oral cavity showing osteocartilaginous
      differentiation have not previously been documented. Primary vaginal melanoma
      with cartilaginous differentiation must be distinguished from primary malignant
      mixed Mullerian tumour whilst malignant change in a pleomorphic adenoma,
      sarcomatoid carcinoma, osteogenic sarcoma and mesenchymal chondrosarcoma are
      included in the differential diagnosis of primary oral mucosal melanomas with
      osteocartilaginous differentiation. In this context, immunohistochemistry using
      antibodies to cytokeratin, S100 protein and MIC2 is of value.

PMID- 9777394
TI  - Male adnexal tumour of probable Wolffian origin occurring in a seminal vesicle.
AB  - AIMS: Adnexal tumours of probable Wolffian origin are rare low-grade malignant
      neoplasms that have been previously described in the broad ligament, ovaries and
      retroperitoneum of females. All are characterized by small, bland epithelial
      cells growing in a diffuse, trabecular, or tubular pattern. The majority of the
      cases reported have pursued a benign clinical course. However, recurrences and
      distant metastases have been described. We present a case of a male adnexal
      tumour of probable Wolffian origin occurring in the left seminal vesicle of a 29
      year-old man with 23 years of follow-up. RESULTS: The diagnosis is supported by
      immunohistochemical and electron microscopic findings: The tumour cells were
      immunoreactive for cytokeratin and vimentin while smooth muscle antigen and S100
      protein were uniformly negative. By electron microscopy cells were arranged in an
      acinar pattern and surrounded flocculent, electron-dense material. Individual
      cells contained numerous dense bodies and free ribrosomes. The patient had
      recurrences at 14 and 23 years after initial diagnosis. CONCLUSION: This is the
      first report of this entity in a male. The literature on this unusual tumour is
      reviewed and the clinicopathological, immunohistochemical and ultrastructural
      features are described. The differential diagnosis of this seemingly indolent
      tumour is discussed with genitourinary tumours having a more aggressive clinical
      course.

PMID- 9777396
TI  - Fixing Indian ink on resection margins.

PMID- 9777395
TI  - Breast development gives insights into breast disease.
AB  - AIMS: Studies of developing human breasts are essential for understanding the
      organogenesis as well as molecular pathogenesis of benign and malignant breast
      diseases. In this study we have examined the distribution of TGF-alpha, TGF-beta
      1, tenascin-C and collagen type IV with the aim of starting to build a picture of
      the profile of molecules that may be involved in the development of the human
      breast. METHODS AND RESULTS: Ten fetal breasts (16 to 23 weeks of gestation) and
      45 infant breasts, ranging in age from newborn to 2 years, were used in this
      study. Paraffin sections from these samples were immunostained with antibodies
      for these proteins and for Ki67 to elucidate the level of proliferative activity
      in different stages of breast development. TGF-alpha immunoreactivity was
      observed both in the stromal and the epithelial cells within fetal and infant
      breasts up to 25 days. TGF-beta 1 immunoreactivity was localized in the
      extracellular matrix. Tenascin-C was found around the neck of the developing
      breast bud and in the extracellular matrix of the infant with peaks in the
      newborn at 6-12 weeks. The immunoreactivity for type IV collagen was more intense
      in the region of the breast bud neck in the fetal breasts and reduced around the
      tips of lobular and terminal-end buds within the infant breasts. CONCLUSIONS: The
      distribution of the growth factors and extracellular matrix proteins within the
      developing human breast indicates that they play a significant role in different
      cellular compartments during morphogenesis and provides insights into breast
      disease.

PMID- 9777397
TI  - Oesophageal sarcoma with CD34 positivity.

PMID- 9777398
TI  - Intimal sarcoma of the left iliac artery.

PMID- 9777399
TI  - Multiple osseous metastases from occult paraganglioma: a diagnostic pitfall.

PMID- 9777400
TI  - Solitary fibrous tumour with an unusual adenofibromatous feature in the lacrimal
      gland.

PMID- 9777401
TI  - Mullerianosis of the urinary bladder: clinical and immunohistochemical findings.

PMID- 9777402
TI  - Cell cycle regulation of hematopoietic stem cells.
AB  - This review focuses on the cell cycle of hematopoietic stem cell and its
      regulatory mechanisms. Owing to recent advances in cell culture techniques and
      analyzing tools, hematopoietic stem cells can be purified from bone marrow,
      peripheral blood, and umbilical cord blood by using specific surface markers such
      as Sca-1 (murine) and CD34 (human). Stem cell compartment includes primitive stem
      cells with self-renewal capacity, multipotential progenitor cells, and lineage
      committed progenitors. The cell cycle profile of each population corresponds to
      their functional status: the most primitive stem cells are dormant (in G0 phase),
      the majority of self-renewing stem cells are in G1 phase and slowly cycling, and
      committed progenitors are rapidly cycling for effective expansion. Recent
      investigations have defined critical components implicated in cell cycle
      regulation of mammalian cells, and those at work for hematopoietic stem cells are
      also becoming clear. It has been reported that cell cycle arrest of stem cells is
      mediated through inhibition of pRB phosphorylation and E2F activity, as well as
      induction of cyclin-dependent kinase (cdk) inhibitors. Negative growth factors
      such as transforming growth factor-beta, macrophage inflammatory protein-1, and
      the interferons may play a role in these events. De-repression of these elements
      by cdk/cyclin complexes, which are activated by colony stimulating factors, is
      associated with the expansion of immature progenitor cells. Further advancement
      in this field should help resolve many of the clinical problems caused by the
      disruption of cell cycle regulation of hematopoietic stem cells.

PMID- 9777403
TI  - Establishment and characterization of melanoma cell line derived from malignant
      melanoma of human uterine cervix.
AB  - A cell line designated HOMM (human Okuno Malignant Melanoma) was established from
      the uterine cervical malignant melanoma of a 65-year-old Japanese woman. The cell
      line has grown well and serial passages were successively carried out 32 times
      within 19 months. The monolayer cultured cells revealed anaplastic and
      pleomorphic features, and grew in multilayers. They had long cell protrusions and
      many dark brown pigments. Immunocytochemical stain revealed that S-100 protein
      existed in the cytoplasm. Electron micrographs also revealed that they had a
      number of pre-melanosomes and melanosomes in the cytoplasm. All cultured cells
      were triploid, the modal chromosome number was 68 and the marker chromosomes were
      presented. The cells were transplanted into an immune-suppressed hamster's cheek
      pouch and produced a malignant melanoma resembled original tumor.

PMID- 9777404
TI  - Structural aspects of collectins and receptors for collectins.
AB  - The collectins are oligomeric molecules composed of C-type lectin domains
      attached to collagen regions via alpha-coiled neck regions. Five members of the
      collectins have been characterized. Mannan-binding lectin (MBL), conglutinin and
      collectin-43 (CL-43) are serum proteins produced by the liver. Lung surfactant
      protein A (SP-A) and lung surfactant protein D (SP-D) are mainly found in the
      lung, where they are synthesized by alveolar type II cells and secreted to the
      alveolar surface. The collectins are believed to play an important role in innate
      immunity. They bind oligosaccharides on the surface of a variety of microbial
      pathogens. After binding of the collectins to the microbial surface effector
      mechanisms such as agglutination, neutralizing or opsonization of the
      microorganisms for phagocytosis are initiated. SP-A and SP-D stimulate chemotaxis
      of phagocytes and once bound to the phagocytes, the production of oxygen radicals
      can be induced. In the case of MBL the opsonization can be further enhanced by
      complement activation via the MBLectin pathway while conglutinin interacts with
      the complement system by binding to the complement degradation product iC3b. A
      number of receptors and binding molecules interacting with the collectins are
      found on the membrane or in association with the membrane of various cells
      responsible for phagocytosis and clearance of microorganisms. This paper focus on
      the structural aspects of the collectins and the receptors for collectins.

PMID- 9777405
TI  - Ficolins and the fibrinogen-like domain.
AB  - Ficolins are a group of proteins containing collagen-like and fibrinogen-like
      (FBG) sequences and they have a similar overall structure to C1q and the
      collectins. There are two types of ficolin in man: L-ficolin and M-ficolin. L
      ficolin is synthesized in the liver and secreted into the plasma. It binds to
      several apparently unrelated structures including sugar residues and enhances
      phagocytosis of bound bacteria. M-ficolin is synthesized mainly in monocytes and
      is detected on the monocyte surface. The polypeptide sequences of ficolins, the
      collectins and C1q diverge mainly in their C-terminal globular regions which are,
      respectively, FBG domains, Ca(2+)-dependent carbohydrate recognition domains (C
      type CRD), and collagen-related sequences. The FBG domain consists of 220-250
      residues and is found in a number of proteins besides fibrinogen and ficolins.
      The crystal structure of the FBG domain has been characterized and the
      elucidation of its binding properties should provide essential insights into its
      role in ficolins and other proteins.

PMID- 9777406
TI  - Functional roles of the lung surfactant proteins SP-A and SP-D in innate
      immunity.
AB  - The surfactant proteins SP-A and SP-D are known to play important roles in innate
      immunity in the lungs in the protection against a wide variety of potential
      pathogens, which include viruses, bacteria and fungi. Recognition of the
      pathogens is, in most cases, mediated by the Ca+2-dependent binding of the C-type
      lectin domains of SP-A, or SP-D, to carbohydrate structures on the surface of the
      microorganisms. This can cause agglutination of the pathogens and also possibly
      their enhanced killing and clearance by phagocytic cells which carry receptors
      for SP-A or SP-D. Both SP-A and SP-D are found in a number of other sites in the
      body, in various secretions, and therefore may play a wider protective role than
      was initially envisaged.

PMID- 9777407
TI  - Interaction of C1q and the collectins with the potential receptors calreticulin
      (cC1qR/collectin receptor) and megalin.
AB  - Several proteins have been identified as candidate cell-surface receptors for the
      complement protein C1q. Some of these also interact with the structurally-related
      collectin proteins. Previous descriptions of C1q-binding properties of cells, and
      information on the cellular distribution of candidate receptors suggest that
      there is more than one physiologically relevant receptor for C1q. Two such
      candidate receptors, cell-surface calreticulin (also referred to as cC1qR or
      collectin receptor) and megalin are discussed in this review.

PMID- 9777408
TI  - Structure and function of gC1q-R: a multiligand binding cellular protein.
AB  - gC1q-R is a 33 kDa, single chain, highly acidic protein, which was first isolated
      from membrane preparation of Raji cells and now appears to be ubiquitously
      distributed. Although, gC1q-R was originally identified as a protein which binds
      to the globular "heads" of C1q, recent evidence suggests that the molecule is in
      fact a multiligand binding, multifunctional protein with affinity for diverse
      ligands which at best are functionally related. These molecules include:
      thrombin, vitronectin, and high molecular weight kininogen. The gC1q-R molecule,
      which is identical to the transcription factors SF2 and the Tat-associated
      protein, or TAP, is the product of a single gene localized on chromosome 17p13.3
      in human, and chromosome 11 in mouse, and is encoded by an approximately 1.5-1.6
      kb mRNA. The full length cDNA encodes a primary translation protein of 282
      residues and the 'mature' or membrane form of the protein isolated from Raji
      cells corresponds to residues 74-282 and is presumed to be generated by a site
      specific cleavage and removal of the highly basic, 73-residues long, N-terminal
      segment during post-translational processing. The translated amino acid sequence
      does not predict for the presence of a conventional sequence motif compatible
      with a transmembrane segment and does not have a consensus site for a GPI anchor.
      However, there is strong evidence which indicates that gC1q-R is expressed both
      inside the cell and on the membrane. First, certain mAbs raised against gC1q-R
      react moderately with intact Raji cells in suspension and this binding increases
      when the cells are first bound to poly-L-lysine coated surfaces and then fixed
      with glutaraldehyde. Second, surface labeling of cells using the membrane
      impermeable sulfo-NHS-LC-biotin shows that gC1q-R on the surface incorporates
      biotin whereas intracellular gC1q-R does not. In addition, the membrane
      expression of gC1q-R can be upregulated with inflammatory cytokines such as INF
      gamma, TNF-alpha, or LPS. These results suggest, that gC1q-R, is localized both
      as an intracellular and as a cell surface protein and may have important
      biological functions in both compartments of the cell.

PMID- 9777409
TI  - Platelet receptors for the complement component C1q: implications for hemostasis
      and thrombosis.
AB  - Platelets participate in a variety of responses of the blood to injury (1). In
      addition to their well known role in hemostasis and thrombosis, platelets play a
      role in inflammation and react with components of the immune system. Immune
      complexes and aggregated IgG, for example, are known to activate platelets via
      ligation of Fc gamma RII receptors and induce the release of platelet granule
      contents, including biogenic amines and adenine nucleotides (2). Platelets also
      interact with the complement subcomponent C1q utilizing binding sites that are
      unrelated to C1s, a complement subcomponent which was originally suggested to
      support C1q binding to thrombocytes (3). The physiologic and pathologic
      consequences of platelet C1q receptor occupancy are incompletely understood.
      Platelet C1q receptors may contribute to immune complex localization and
      clearance, as has been suggested for C1q receptors on phagocytic cells (4), but
      considerable evidence is emerging to suggest that the interaction between C1q and
      platelets may influence hemostasis and perhaps, more profoundly, thrombotic
      complications resulting from immune injury. This review will summarize current
      concepts in C1q receptor biology as it relates to human platelet function and
      blood coagulation.

PMID- 9777410
TI  - C1q receptors: regulating specific functions of phagocytic cells.
AB  - A C1q receptor that upregulates the phagocytic capacity of professional
      phagocytes, C1qRp, has been identified, and its primary structure determined by
      cDNA cloning and sequencing. Monoclonal antibodies that immunoprecipitate this
      126,000 Mr polypeptide inhibit the enhancement of phagocytosis triggered not only
      by C1q but also by mannose binding lectin (MBL) and pulmonary surfactant protein
      A (SPA) providing critical evidence that this polypeptide is a functional
      receptor or component of the receptor that mediates this enhancement of
      phagocytosis. The amino acid sequence, deduced from the cloned cDNA coding for
      this receptor, indicates that this surface glycoprotein receptor is a novel type
      I membrane protein of 631 amino acid containing a region homologous to C-type
      lectin carbohydrate recognition domains, 5 EGF-like domains, a single
      transmembrane domain and a 47 amino acid intracellular domain. Expression of this
      receptor is limited to cells of myeloid origin, platelets and endothelial cells,
      consistent with a relatively selective function, and making it an attractive
      candidate for therapeutic modulation of function. A distinct C1q receptor that
      triggers superoxide in polymorphonuclear leukocytes has been functionally
      characterized and designated as C1qRO2-. Thus, the accumulated data that will be
      summarized here demonstrate that there are at least two C1q receptor/receptor
      complexes (C1qRp and C1qRO2-), each triggering distinct cellular responses, that
      multiple C1q receptors can be expressed on the same, as well as on different,
      cell types, and that at least one C1q receptor, C1qRp, is capable of responding
      to multiple ligands.

PMID- 9777411
TI  - C1q and systemic lupus erythematosus.
AB  - In this chapter we review the association between SLE and C1q. In the first part
      of the chapter we discuss the clinical associations of C1q deficiency, and
      tabulate the available information in the literature relating to C1q deficiency
      and autoimmune disease. Other clinical associations of C1q deficiency are then
      considered, and we mention briefly the association between other genetically
      determined complement deficiencies and lupus. In the review we explore the
      relationship between C1q consumption and lupus and we discuss the occurrence of
      low molecular weight (7S) C1q in lupus, which raises the possibility that
      increased C1q turnover in the disease may result in unbalanced chain synthesis of
      the molecule. Anti-C1q antibodies are also strongly associated with severe SLE
      affecting the kidney, and with hypocomplementaemic urticarial vasculitis, and
      these associations are also examined. We address the question of how C1q
      deficiency may cause SLE, discussing the possibility that this may be due to
      abnormalities of immune complex processing, which have been well characterised in
      a umber of different human models. There is clear evidence that immune complex
      processing is abnormal in patients with hypocomplementaemia, and this is
      compatible with the hypothesis that ineffective immune complex clearance could
      cause tissue injury, and this may in turn stimulate an autoantibody response. We
      have also considered the possibility that C1q-C1q receptor interactions are
      critical in the regulation of apoptosis, and we explore the hypothesis that
      dysregulation of apoptosis could explain important features in the development of
      autoimmune disease associated with C1q deficiency. An abnormally high rate of
      apoptosis, or defective clearance of apoptotic cells, could promote the
      accumulation of abnormal cellular products that might drive an autoimmune
      response. Anti-C1q antibodies have been described in a number of murine models of
      lupus, and these are also briefly discussed. We focus on the recently developed
      C1q "knockout" mice, which have been developed in our laboratory. Amongst the C1q
      deficient mice of a mixed genetic background high titres of antinuclear
      antibodies were detected in approximately half the animals, and around 25% of the
      mice, aged eight months had evidence of a glomerulonephritis with immune
      deposits. Large numbers of apoptotic bodies were also present in diseased
      glomeruli, and this supports the hypothesis that C1q may have a critical role to
      play in the physiological clearance of apoptotic cells.

PMID- 9777412
TI  - Molecular basis of hereditary C1q deficiency.
AB  - Complete selective deficiencies of the complement component C1q are rare genetic
      disorders which are associated with recurrent infections and a high prevalence of
      lupus erythematosus-like symptoms. The improvements in molecular biology
      techniques have facilitated the analysis of such genetic defects to a great
      extend. To date the basis of C1q deficiencies from 13 families have been studied
      at the genetic level. In each case single base mutations leading to either
      termination codons, frame shift or amino acid exchanges were thought to be
      responsible for these defects as no other aberrations were found. In addition to
      DNA analysis, conventional immunochemical and biochemical methods have
      contributed substantially to the elucidation of the structural and functional
      requirements of this complex macromolecule. The present article reviews the
      different types of C1q defects in regard to structure and function whereas a
      detailed presentation on the clinical aspects of C1q deficiencies will be given
      in this issue of the Journal (by WALPORT, DAVIES and BOTTO).

PMID- 9777413
TI  - C1q as antigen in humoral autoimmune responses.
AB  - The observation of anti-C1q antibodies (C1qAb) in patients with various
      autoimmune diseases has led to the establishment of a strong correlation between
      these antibodies and renal involvement in patients with systemic lupus
      erythematosus (SLE). The measurement of anti C1q antibodies requires detailed
      insight in the reactivity of C1q with immune complexes and the methods to detect
      C1q as an antigen by solid phase assays. In this overview we describe the
      pitfulls of the anti C1qAb assay and its use in the measurement of C1qAb. Further
      we discuss the relevance of C1qAb in the pathogenesis of SLE and especially in
      relation to lupus nephritis.

PMID- 9777414
TI  - Structural and functional studies on C1r and C1s: new insights into the
      mechanisms involved in C1 activity and assembly.
AB  - C1r and C1s, the enzymes responsible for the activation and proteolytic activity
      of the C1 complex of complement, are modular serine proteases featuring similar
      overall structural organizations, yet expressing very distinct functional
      properties within C1. This review will initially summarize available information
      on the structure and function of the protein modules and serine protease domains
      of C1r and C1s. It will then focus on the regions of both proteases involved in:
      (i) assembly of C1s-C1r-C1r-C1s, the Ca(2+)-dependent tetrameric catalytic
      subunit of C1; (ii) expression of C1 catalytic activities. Particular emphasis
      will be aid on recent structural and functional studies that provide new insights
      into the complex mechanisms involved in the assembly, activation, and proteolytic
      activity of C1.

PMID- 9777415
TI  - Structure and function of the serine-protease subcomponents of C1: protein
      engineering studies.
AB  - Our protein engineering studies on human C1r and C1s revealed important
      characteristics of the individual domains of these multidomain serine-proteases,
      and supplied evidence about the cooperation of the domains to create binding
      sites, and to control the activation process. We expressed the recombinant
      subcomponents in the baculovirus-insect cell system and checked the biological
      activity. Deletions and point mutants of C1r were constructed and C1r-C1s
      chimeras were also produced. Our deletion mutants demonstrated that the N
      terminal CUB domain and the EGF-like domain of C1r together are responsible for
      the calcium dependent C1r-C1s interaction. It seems very likely that these two
      modules form the calcium-binding site of the C1r alpha-fragment and participate
      in the tetramer formation. The deletion mutants also demonstrated that the N
      terminal region of the C1r molecule contains essential elements involved in the
      control of activation of the serine-protease module. The substrate specificity of
      the serine-protease is also determined by the five N-terminal noncatalytic domain
      of C1r/C1s chimera, which contains the catalytic domain of C1s preceded by the N
      terminal region of C1r, could replace the C1r in the hemolytically active C1
      complex. The C1s/C1r chimera, in which the alpha-fragment of the C1r was replaced
      for that of the C1s exibits both C1r- and C1s-like characteristics. We stabilized
      the zymogen form of human C1r by mutating the Arg(463)-Ile(464) bond. Using our
      stable zymogen C1r we showed that one active C1r in the C1 complex is sufficient
      for the full activity of the entire complex. Further experiment with this mutant
      could provide us with important information about the structure of the C1
      complex.

PMID- 9777416
TI  - Mannose-binding lectin (MBL) in health and disease.
AB  - Mannose-binding lectin (MBL) is the most intensively studied human collectin. It
      is recognized to be a versatile macro-molecule with many of the functional
      characteristics of IgM, IgG and Clq. In the presence of calcium the protein can
      bind to a wide spectrum of oligosaccharides through multiple lectin domains. Such
      binding to the repeating sugar arrays on microbial surfaces may result in direct
      uptake by one or more collectin receptors on phagocyte surface or may trigger the
      activation of a pro-serine protease complex (MASP 1 and MASP 2) leading to
      cleavage of C4 and C2 of the classical complement pathway. Although serum levels
      of MBL are normally rather low (1500 micrograms/litre) there is increasing
      evidence that the protein plays an important role in immune defence, particularly
      during the phase of primary contact with a microorganism. This is suggested by
      the observed association of an increased incidence of infections in individuals
      with structural mutations in exon 1 of the MBL gene. A cluster of such mutations
      in codons 52, 54 and 57 lead to secondary structural abnormalities of the
      collagenous triple helix and a failure to form biologically functional higher
      order oligomers. The codon 54 mutation has been identified in several Eurasian
      populations whereas the codon 57 mutation is characteristic of sub-Saharan
      populations. One intriguing paradox arising from the MBL genotyping studies is
      the observation that in many populations there are surprisingly high frequencies
      of either the codon 54 or codon 57 mutation, suggesting that there may be some
      biological advantage associated with absence of the protein. Nevertheless,
      various groups have reported either low serum levels of MBL or an increased
      frequency of the structural gene mutations in patients with suspected
      immunodeficiencies, those with frequent unexplained infections and those with
      systemic lupus erythematosus. There is also evidence that the rate of progression
      of AIDS in HIV positive men is faster in those with such mutations. A recently
      published study of a consecutive series of admissions to a paediatric unit
      suggests that children presenting with an infectious aetiology are significantly
      more likely to have a MBL mutation. Moreover, this association was independent of
      age. Prospective studies are underway to address the questions raised by these
      findings.

PMID- 9777417
TI  - MASP1 (MBL-associated serine protease 1).
AB  - Mannose-binding lectin (MBL) is a serum component which participates in innate
      immunity by activating complement via a novel pathway. Human MBL forms complexes
      with two types of serine proteases termed MASP (MBL-associated serine protease).
      These two proteases, MASP1 and MASP2, are structurally similar to one another as
      well as to C1r and C1s. Together, MASP, C1r and C1s constitute a novel serine
      protease family. It is likely that human MASP1 is able to activate C3, while
      human MASP2 cleaves C4, although further functional studies are required to
      confirm this. Based on the analysis of MASP cDNA of vertebrates and ascidians,
      the MASP/C1r/C1s family can be classified into two groups. The first group is
      characterized by a histidine loop in its serine protease domain, an active-center
      serine encoded by TCN, and a proline as the amino acid residue at the-3 position
      from the active serine. Human MASP1, mouse MASP1, Xenopus MASP1 and ascidian
      MASPs all belong to this group. MASP of the second group has structural features
      which are distinct from those of the first group: an absence of a histidine loop,
      an active-serine encoded by AGY, and an alanine or valine as the amino acid
      residue at the -3 position from the active-serine. The second group includes
      human MASP2, Xenopus MASP2, carp MASP, shark MASP, C1r and C1s. The TCN-type of
      MASP may have emerged prior to the AGY-type as an ancestral protease of the
      MASP/C1r/C1s family and played a crucial role in cleaving C3.

PMID- 9777418
TI  - MASP-2, the C3 convertase generating protease of the MBLectin complement
      activating pathway.
AB  - Mannan-binding lectin (MBL) activates the complement system through cleavage of
      C4 and C2. Until recently it was thought that only one serine protease in complex
      with MBL (MBL-associated serine protease, MASP) mediates complement activation,
      but with the finding of a second MBL-associated serine protease, MASP-2, the
      activation process appears more elaborate, possibly resembling that of the C1
      complex. The two MASPs share the domain organisation of C1r and C1s and it may be
      speculated that interaction between the two MASPs is required for complement
      activation in the same manner as with the C1 proteases. We have demonstrated that
      MASP-2 is a C4 cleaving component of the MBL/MASP complex. By analogy, one may
      thus speculate that, upon binding of MBL to carbohydrate, MASP-1 autoactivates
      and then activates MASP-2, but there is as yet no evidence for this. The
      components of C1 are present in serum in approximately equimolar amounts, whereas
      MASP-1 is in large excess over MBL. Pairwise comparison of the four proteases
      shows the primary structures to be approximately 40% identical. Phylogenetic
      analysis indicates that MASP-2 is closer to C1r and C1s than is MASP-1, but no
      particular association between MASP-2 and the C4 cleaving enzyme, C1s, can be
      deduced from sequence comparison.

PMID- 9777419
TI  - Molecular genetics of C1 inhibitor.
AB  - More than 100 different C1 inhibitor gene mutations have been described in
      hereditary angioedema (HAE) patients. Sixty-nine mutations have been reported in
      patients with the quantitative C1 inhibitor defect (type 1 HAE) in two recent
      large-scale studies. These changes were found distributed over all exons and
      exon/intron boundaries. The molecular defects can be divided as follows: Alu
      repeat-mediated deletions or duplications (accounting for 21% of all cases),
      missense mutations (> 36%), frameshifts (14%), Stop codon mutations (10%),
      promoter variants (4%), splice site mutations (7-10%), deletions of a few amino
      acids (less than 3%). Several recent studies indicate that up to 25% of these
      changes are found in patients without a family history of angioedema and
      represent de novo mutations. Pathogenic amino acid substitutions were found
      distributed over the entire length of the coding sequence, except for the 100
      amino-acid-long glycosylated amino-terminal extension, whose sequence tolerates
      extensive variation, as indicated by comparisons across species. Functional
      studies have been carried out only on a fraction of these amino acid
      substitutions and indicate that defects affecting intracellular transport are
      often at the basis of type 1 hereditary angioedema. An interesting promoter
      variant (a C to T transition at position -103) was found in an exceptional family
      with recessive transmission of the disease. Regulatory elements in the promoter
      region and in intron 1 were revealed by their sequence conservation in mouse and
      man and by functional studies. C1 inhibitor "minigene" constructs directing
      correct mRNA and protein synthesis in transgenic mice have provided valuable
      information on hormonal control and cell-type specificity of gene expression.

PMID- 9777420
TI  - Pathogenetic and clinical aspects of C1 inhibitor deficiency.
AB  - People deficient in C1-INH present recurrent angioedema localized to subcutaneous
      or mucous tissues. The defect can be caused by impaired synthesis, due to a
      genetic defect (hereditary angioedema), or by increased catabolism (acquired
      angioedema). In our experience the majority of patients with acquired angioedema
      (16 of 18) have autoantibodies to C1-INH in their serum. These autoantibodies
      bind to C1-INH with different and generally low affinity. The vasopermeability
      mediator responsible for attacks is still undefined: bradykinin (derived from
      cleavage of high molecular weight kininogen) and a kinin-like peptide (derived
      from the second component of complement) still remain the two primary candidates.
      We examined the systems controlled by C1-INH (complement, contact system,
      fibrinolysis and coagulation) and found that all of them are activated during
      angioedema attacks. Activation of the coagulation leads to generation of thrombin
      whose vasoactive effect can thus influence edema formation. Treatment of severe
      angioedema attacks is satisfactorily performed with C1-INH plasma concentrate
      although patients with an acquired defect frequently need very high doses.
      Attenuated androgens effectively prevent attacks in hereditary angioedema, but
      their safety, on the very long-term, needs to be further assessed. Acquired
      angioedema generally fail to respond to these drugs, but can be treated
      prophylactically with antifibrinolytic agents.

PMID- 9777421
TI  - Regulation of C1 inhibitor synthesis.
AB  - The primary biologic roles of C1 inhibitor (C1-INH) are the regulation of
      activation of the classical complement pathway and of the contact system of kinin
      formation. Heterozygosity for deficiency or dysfunction of C1-INH results in
      hereditary angioedema (HAE). This deficiency results in loss of homeostasis with
      unregulated complement and contact system activation. Due to the consequent C1
      INH consumption, plasma levels of C1-INH in patients with HAE are decreased below
      50% of normal. In addition, diminished synthesis contributes to the lowered
      levels in some patients. The hepatocyte is the primary source of C1-INH, although
      a number of other cell types, including peripheral blood monocytes, microglial
      cells, fibroblasts, endothelial cells, the placenta, and megakaryocytes also
      synthesize and secrete the protein both in vivo and in vitro. Interferon-gamma
      and alpha (IFN), colony stimulating factor-1, interleukin-6 (IL-6) and tumor
      necrosis factor-alpha (TNF-alpha) all induce C1-INH synthesis in a variety of
      cell types. The IFN-response elements in the 5'-flanking region and in the first
      intron have been partially characterized, as have several of the promoter
      elements that direct basal transcription of the gene. However, although androgen
      therapy, in vivo, results in an increase in C1-INH plasma levels, a direct effect
      of androgens on C1-INH synthesis has not been convincingly demonstrated. Although
      the C1-INH gene contains a potential glucocorticoid/androgen response element,
      this element does not appear to respond to androgen. Continued analysis of the
      transcriptional regulation of the C1-INH gene may lead to new approaches to
      therapy of HAE.

PMID- 9777422
TI  - Are genetic factors important in the aetiology of leukoaraiosis? Results from a
      memory clinic population.
AB  - OBJECTIVE: To discover whether polymorphism in either the apolipoprotein E (ApoE)
      or angiotensin-converting enzyme (ACE) genes is associated with leukoaraiosis,
      white matter lesions visible on neuroimaging of the brain, which is commonly seen
      in dementia as well as some normal elderly subjects. DESIGN: Prospective study of
      consecutive patients attending our memory disorders clinic, to examine the
      relationship between leukoaraiosis and polymorphism of the ApoE and ACE genes.
      SETTING: Memory disorders clinic in Bristol, UK. PATIENTS: 182 patients attending
      the memory disorders clinic for investigation of possible dementia of whom 75%
      were suffering from dementia, 20% from memory impairment but no dementia and in
      5% of whom a dementing illness was thought to be unlikely; 38% of all patients
      had visible white matter lesions and 16% had cerebral infarcts. MEASURES:
      Patients and/or carers who agreed to participate in the study had their ACE and
      ApoE genotype determined and their brain CT/MRI scans were assessed by a
      neuroradiologist, blind to the result of the genotyping, for the presence or
      absence of white matter low attenuation. RESULTS: There was a significant
      association between white matter lesions and the DD genotype (p < 0.05), but not
      the ApoE genotype. However, this relationship with the DD genotype was only
      significant for patients with a previous infarct. CONCLUSION: Homozygosity of ACE
      gene deletion polymorphism is a risk factor for white matter lesions when it is
      associated with cerebral infarction. This suggests that it may be possible to
      identify subjects who are at greater risk of developing white matter lesions and
      are at risk of cognitive impairment and possibly dementia.

PMID- 9777423
TI  - The natural history of mental disorder in old age: Alzheimer's disease and
      depressive illness compared.
AB  - BACKGROUND: Depressive illness (DI) and Alzheimer's disease (AD) are important
      causes of morbidity in old age and the relationships between these two disorders
      are uncertain. METHOD: In a prospective, descriptive, comparative study of
      consecutive referrals aged over 65 years to one consultant, 218 patients with AD
      and 280 patients with DI were followed up for 15 years. RESULTS: The prognosis of
      DI uncomplicated by physical illness at referral was reasonably good and 5-year
      survival was double that of AD. The rate of occurrence of AD in DI is no greater
      than in the general population. The higher mortality from cancer in DI than in AD
      is unexplained but may relate to differences in aetiology of these two disorders.
      CONCLUSION: Although their symptoms frequently overlap, AD and DI are distinct
      disorders with very different prognoses and accurate diagnosis may have important
      implications for appropriate treatment.

PMID- 9777424
TI  - Outcomes following acute hospital care for stroke or hip fracture: how useful is
      an assessment of anxiety or depression for older people?
AB  - OBJECTIVE: To investigate the association between severe life events and mental
      health outcomes following acute hospital care for older patients with acute
      stroke or fractured neck of femur. DESIGN: Prospective longitudinal survey of
      stroke and hip fracture patients admitted to hospital from admission to 6-month
      follow-up. SETTING: Six district general hospitals, three in the North and three
      in the South of England. PARTICIPANTS: 642 patients admitted to hospital with an
      acute stroke (268) or hip fracture (374) resident in a private household at 6
      months follow-up. MAIN OUTCOME MEASURES: Hospital Anxiety and Depression Scale,
      cognitive items of the Survey Psychiatric Assessment Scale, Clackmannan
      Disability Scale, Severe Life Events Inventory, Wenger Social Support Network
      Typology. RESULTS: 47% of 6-month survivors of stroke or hip fracture resident in
      private households had a possible psychiatric illness: dementia (13%), anxiety or
      depression (41%). 57% had severe or very severe disability and 48% experienced
      additional life events (17% two or more) after hospital admission. Severe
      disability was strongly associated with a higher prevalence of anxiety (p <
      0.0005) or depression (p < 0.0001). Social contact was associated with a lower
      prevalence of anxiety (p < 0.01) or depression (p < 0.0001) and social support
      network type was strongly associated with depression (p < 0.001) but not anxiety
      (p = 0.096). Number of severe life events was associated with anxiety (p < 0.001)
      but not depression (p = 0.058). CONCLUSION: Disability is probably a more robust
      outcome measure than assessments of mental health for older people in
      uncontrolled studies.

PMID- 9777425
TI  - Randomized trial of the effect of supplementation on the cognitive function of
      older people with subnormal cobalamin levels.
AB  - BACKGROUND: Low serum cobalamin levels are often found in apparently normal older
      subjects. A major worry of leaving cobalamin deficiency untreated is that it may
      lead to subtle deterioration in cognitive function. OBJECTIVES: To investigate
      the effect of supplementation on the cognitive function of older people with
      cobalamin deficiency by a randomized trial. METHODS: Fifty Chinese subjects more
      than 60 years old with serum cobalamin level < 120 pmol/l were randomized into
      supplement and control groups. Fasting serum methylmalonic acid levels (MMA) were
      measured. A battery of neuropsychological tests was administered. The supplement
      group received intramuscular cyanocobalamin injections, while the control group
      received no intervention. They were followed up at around 4 months. RESULTS: 78%
      of the subjects had raised MMA, indicating metabolic cobalamin deficiency.
      Supplemented subjects improved in performance IQ, but the amount of improvement
      was not significantly more than that of control subjects. Moreover, the
      supplement group fared worse than the control group at follow-up in some motor
      function scores. Three out of seven demented subjects had improvement in Mini
      Mental State Examination scores, but there was no consistent improvement in other
      neuropsychological scores. CONCLUSIONS: This study suggested that cobalamin
      deficiency did not invariably cause cognitive impairment in older people. There
      remain the possibilities that cobalamin deficiency causes cognitive impairment or
      exacerbates coexisting dementia in some older people.

PMID- 9777426
TI  - Do health and use of services differ in residents of sheltered accommodation? A
      pilot study.
AB  - OBJECTIVE: To compare the rates of mental health problems, disability and use of
      health and social services of older people living in sheltered accommodation with
      those of the rest of the community in the same age group. DESIGN: Door-to-door
      survey in randomly selected enumeration districts. The districts contained three
      sheltered accommodation complexes. Residents from these addresses were compared
      with the others. SETTING: London Borough of Islington. SUBJECTS: 700 men and
      women aged 65 or over. MAIN OUTCOME MEASURES: Short-CARE depression, dementia and
      activity scales; the Guy's/Age Concern anxiety scale; individual items detailing
      problems with mobility, vision and hearing; use of a number of health and social
      services. RESULTS: The only difference in mental health variables on univariate
      analysis was a greater severity of cognitive impairment and dementia symptoms in
      sheltered accommodation. When demographic differences were taken into account,
      the association with cognitive impairment became statistically insignificant.
      There were significant associations between residence in sheltered accommodation
      and several of the disability variables. Increased use of health and social
      services by sheltered residents remained significant after disability and living
      alone were taken into account. CONCLUSIONS: The residents of sheltered
      accommodation were more disabled than the general elderly population but, in
      contrast to those in residential care, did not have a great excess of mental
      health problems. Indeed, the possibility was raised that sheltered accommodation
      may protect against depression in people who live alone.

PMID- 9777427
TI  - Effect of gender and apolipoprotein E genotype on response to anticholinesterase
      therapy in Alzheimer's disease.
AB  - BACKGROUND: Anticholinesterase therapies offer modest benefit to subgroups of AD
      sufferers. However, there has previously been no way of predicting which patients
      will respond to any of the drugs. OBJECTIVE: To discover if gender and/or
      apolipoprotein E genotype can be used as predictors of response in the clinical
      setting. DESIGN: 107 patients from the Bristol Memory Disorders Clinic took part
      in a double-blinded or open label trial of tacrine therapy for between 3 and 12
      months or an open label trial of galanthamine therapy for 3 months. RESULTS:
      After 3 months of therapy, gender was found to be the only significant influence
      on the number of responders to anticholinesterase therapy. Men had a 73% greater
      chance of responding than women (p = 0.012). While ApoE genotype did not modify
      response to therapy in the short term, there are indications that it may affect
      response over the longer term (up to 12 months), and also that the initial
      advantage of male gender may not be maintained after 3 months. CONCLUSION: Gender
      is likely to be a more powerful determinant of outcome of anticholinesterase
      treatment than apolipoprotein E status in the short term.

PMID- 9777428
TI  - An epidemiological profile of elderly suicides in Hong Kong.
AB  - Suicide rates in Hong Kong increased with age, and the highest suicide rate
      occurred among the oldest age groups. Hong Kong has one of the highest elderly
      suicide rates in the world. The elderly suicide rate was four to five times above
      the average. Furthermore, gender differences were observed among different
      marital status groups. For example, single males had a much higher rate than
      single females and married males had a higher rate than their widowed
      counterparts. The suicide rate for an economically inactive person was six times
      higher than for an active one. Jumping has become increasingly common and seems
      to substitute for other methods of suicide. Winter months and the Chinese New
      Year period had the lowest suicide occurrence. Some explanations are given.

PMID- 9777429
TI  - An unusual case of pica.
AB  - Pica is the persistent, culturally and developmentally inappropriate ingestion of
      non-nutritive substances (DSM-IV). AB is a 75-year-old lady with a 40-year
      history of schizophrenia and a 20-year history of pica who, at emergency
      laparotomy, had 175.32 Pounds of loose change in her stomach. Although pica has
      been reported to coexist with schizophrenia, she had had no positive symptoms of
      schizophrenia for at least 20 years. She has CT evidence of fronto-tempotal
      atrophy most marked on the left in the temporal lobe and on the right in the
      frontal lobe. Pica has been found to be related to cognitive deficits and
      hyperoral behaviour to temporal lesions. Neuropsychological testing reveals
      deficits closely related to these changes.

PMID- 9777430
TI  - Demented and chronic depressed patients attending a day hospital: stress
      expressed by carers.

PMID- 9777431
TI  - A case report of two siblings with familial leukoencephalopathy in normotensive
      male adults with alopecia and lumbago.

PMID- 9777432
TI  - Capgras syndrome in the context of multiple myeloma.

PMID- 9777434
TI  - Current awareness in geriatric psychiatry.

PMID- 9777433
TI  - Monitoring cognitive disturbance in delirium with the ten-point clock test.

PMID- 9777435
TI  - Utility of the Maternal Perinatal Scale (MPS) in distinguishing normal from
      learning disabled children.
AB  - This study examined perinatal complications and risk factors as predictors of
      learning disabilities in schoolaged children. Specifically, the Maternal
      Perinatal Scale (MPS) was used to distinguish between normal children and those
      classified as learning disabled (LD) by their school system. One hundred and
      eight participants, 54 in each classification, were selected from a small
      Midwestern area. A stepwise discriminant analysis demonstrated that all four
      factors of the MPS contribute significantly to the prediction. A linear composite
      of MPS factor scores correctly classified 93.5% of all participants, with only
      two normal and five LD children being misclassified. Repeating the results with
      other clinical populations, these results support the use of the MPS in assessing
      the perinatal history. More importantly, these data are consistent with the
      notion that perinatal complications increase the likelihood of future impairment.
      Moreover, the MPS shows promise as a screening device for use in early
      preventative programs which diminish the negative psychological, sociological,
      and neuropsychological outcomes for children with neurological disorders.

PMID- 9777436
TI  - Fast and slow reaction times and associated ERPs in patients with schizophrenia
      and controls.
AB  - A number of studies have examined across-trial averaged late component. Event
      Related Potentials (EPR) and Reaction Times (RT) in response to multiple target
      stimuli. In this study, within-trial relatively fast and slow sub averages are
      additionally examined, in 20 patients with schizophrenia and 20 age and sex
      matched controls. A conventional auditory oddball paradigm. Across-trial ERP
      average analysis showed smaller N200 amplitude and delayed latency (but larger
      P200 amplitude) in patients with schizophrenia compared with controls. Within
      trial ERP analysis revealed a number of additional findings. Controls showed
      distinctive differences in fast compared with slow ERP sub averages (smaller P200
      amplitude, increased N200/P300 amplitudes and earlier latencies). The
      schizophrenic group on the other hand, showed relatively similar fast versus slow
      subaverages (no differences in P200 amplitude and N200 latency). In addition,
      between-group (within-trial) analyses highlighted significant differences in
      earlier stages of processing (compared with across-trial averages) in both fast
      and slow subaverages (increased N100 amplitude in controls). The complementary
      within-trial (compared with across-trial) data are interpreted with respect to a
      possible disturbance in inhibitory function in patients with schizophrenia.

PMID- 9777438
TI  - Shorter latencies of components of middle latency auditory evoked potentials in
      congenitally blind compared to normal sighted subjects.
AB  - A previous study which reported shorter latencies of the Nb component of AEP-MLRs
      in congenitally blind compared to normal sighted subjects, formed the basis for
      the present study. The blind subjects had received a rehabilitation program from
      the age of 4 years onwards, which may have influenced auditory function. Hence
      the present study was designed to compare the AEP MLRs of normal sighted subjects
      with age-matched blind subjects who had not undergone early rehabilitation.
      Auditory evoked potentials (0 to 100 ms. range) were recorded in 10 congenitally
      blind subjects (average age = 22.4 +/- 4.9 yrs.) and an equal number of age
      matched subjects with normal vision. There were two repetitions per subject. The
      peak latencies of both the Pa (maximum positive peak between Na and 35 ms.) and
      Nb (maximum negative peak between 38 and 52 ms.) waves was significantly shorter
      in congenitally blind compared to normal sighted subjects. Since the Pa and Nb
      waves are believed to be generated by the superior temporal cortex (Heschl's
      gyrus), it appears that processing at this neural level occurs more efficiently
      in the blind. Also, in spite of the absence of an early rehabilitation program
      the present subjects showed the same auditory changes as those reported earlier.

PMID- 9777437
TI  - Premorbid psychosocial behavior in demented patients.
AB  - We investigated the premorbid behavioral characters of demented patients in terms
      of life style, type A behavior, life events and coping behavior. We adopted the
      case control study. Significant differences were not found in the inventory
      scores of life style, passive coping behavior and type A behavior between
      dementia group and normal controls. However, the life events occurred
      significantly frequent in the vascular dementia group and the score of positive
      coping behavior was significantly low in dementia group. The results suggest that
      those life events and positive coping behavior might be related to the onset of
      dementia.

PMID- 9777439
TI  - Sex differences in naturally occurring leg muscle pain and exertion during
      maximal cycle ergometry.
AB  - This investigation examined the role of sex in perceptions of leg muscle pain
      during exercise. Males (N = 26; age = 23.2 +/- 3.9) and females (N = 26; age =
      21.9 +/- 3.5) matched on weekly energy expenditure completed a ramped maximal
      cycle ergometry test. Leg muscle pain thresholds were determined and pain
      intensity ratings as well as ratings of perceived exertion were obtained during
      and after exercise. The power output at pain threshold was lower in females
      (129.9 +/- 46.5 watts) compared to males (148.2 +/- 56.6 watts). Peak power
      output and peak pain intensity ratings were lower (P < 0.001) in females (211.3
      +/- 39.1 watts; 5.5 +/- 2.9) compared to males (303.6 +/- 27.5 watts; 8.5 +/-
      2.3). A Sex X Relative Intensity (i.e., % peak power output) ANOVA revealed that
      females reported lower pain ratings at each relative intensity examined (F =
      17.7; df = 1.50; p < 0.001). The primary conclusion of this investigation is that
      females rate naturally occurring leg muscle pain as less intense than males when
      data are relativized to peak power output.

PMID- 9777441
TI  - The prenatal attenuation of brain/body development through interactions between
      growth hormone, triiodothyronine and testosterone during prenatal development of
      female neonates.
AB  - The relations of serum growth hormone (GH), free testosterone (T), and free
      triiodothyronine (T3) concentrations to the head circumference, height, and
      weight were studied in the human neonates. Blood was taken from the umbilical
      cord immediately after the birth, to measure the hormone concentrations. GH was
      found to be inversely correlated with the bodily measures in the female neonates;
      there were no significant correlations between these variables in males. In
      females, free T3 negatively linearly correlated with GH, and positively linearly
      correlated with the neonatal head circumference, height, and weight. Serum free T
      levels was found to be positively linearly correlated with GH, and negatively
      linearly correlated with the neonatal body measures in the same subjects. It was
      suggested that GH may exert growth reducing effects through T3 and T during
      perinatal development.

PMID- 9777440
TI  - Importance of immunological and inflammatory processes in the pathogenesis and
      therapy of Alzheimer's disease.
AB  - The contribution of autoimmune processes or inflammatory components in the
      etiology and pathogenesis of Alzheimer's disease (AD) has been suspected for many
      years. The presence of antigen-presenting, HLA-DR-positive and other
      immunoregulatory cells, components of complement, inflammatory cytokines and
      acute phase reactants have been established in tissue of AD neuropathology.
      Although these data do not confirm the immune response as a primary cause of AD,
      they indicate involvement of immune processes at least as a secondary or tertiary
      reaction to the preexisting pathogen and point out its driving-force role in AD
      pathogenesis. These processes may contribute to systemic immune response. Thus,
      experimental and clinical studies indicate impairments in both humoral and
      cellular immunity in an animal model of AD as well as in AD patients. On the
      other hand, anti-inflammatory drugs applied for the treatment of some chronic
      inflammatory diseases have been shown to reduce risk of AD in these patients.
      Therefore, it seems that anti-inflammatory drugs and other substances which can
      control the activity of immunocompetent cells and the level of endogenous immune
      response can be valuable in the treatment of AD patients.

PMID- 9777442
TI  - Changes of the EEG paroxysmal pattern during felbamate therapy in Lennox-Gastaut
      syndrome: a case report.
AB  - We report a case of a 43-year old woman with Lennox-Gastaut syndrome who
      exhibited atypical absence seizures, atonic seizures and generalized toniclonic
      seizures which were not controlled by antiepileptic drug (AED) treatment. Because
      of this, felbamate (FBM) (1800 mg per day) was progressively added to the pre
      existent therapy. The patient underwent a 24-hour-video-EEG monitoring before and
      after 4 months of FBM therapy. Analysis of the video-EEG signal recorded during
      wakefulness revealed the presence of ictal activity represented by repetitive,
      bilateral, slow spike and wave bursts underlying atypical absence seizures; the
      ictal activity occurring during non-REM sleep was characterized by runs of
      bilateral, rapid, high-voltage spikes followed by slow spike and wave complexes
      corresponding to brief tonic seizures. FBM therapy induced disappearance of the
      EEG ictal slow, spike and wave complexes leaving rather unaffected the runs of
      spikes. Computerized analysis of both the EEG background activity and the sleep
      structure displayed a better organization of the global cerebral rhythms under
      FBM treatment. Our findings suggest a selective effect of FBM on the ictal
      atypical spike and wave pattern. The differential effect of FBM on ictal patterns
      may be a reflection of a different action on the excitatory and inhibitory
      systems.

PMID- 9777444
TI  - Individual differences in memory and executive function abilities during normal
      aging.
AB  - The purpose of this study was to analyze the effects of some individual variables
      on memory and executive function test performance in normal aging individuals.
      Sixty subjects (21 males and 39 females), with a mean age of 69.66 (SD = 7.09)
      were selected. The following neuropsychological tests were selected. The
      following neuropsychological tests were administered: Associative Learning and
      Logical Memory from the Wechsler Memory Scale (WMS) (Wechsler, 1945), Associative
      Memory with Semantic Enhancement Test (AMSET) (Pineda, Galeano and Giraldo,
      1991), Wisconsin Card Sorting Test (WSCT) (Heaton, 1981), and Verbal Fluency
      (phonologic and semantic). The effects of demographic (age, education, and sex)
      and some individual variables (academic history, working history, physical
      activity, and leisure activities) were measured. Age and education effects on
      test scores were observed, but no sex effect was found. Working history and
      leisure activities established significant differences in some test scores. A
      multiple regression analysis was performed. Not only demographic variables, but
      also individual variables were associated with memory, and albeit at a lesser
      extend, with executive function test scores. It was emphasized that not only
      demographic factors, but also individual variables have a significant effect on
      cognitive changes observed during normal aging.

PMID- 9777443
TI  - Reversal of the bicycle drawing direction in Parkinson's disease by AC pulsed
      electromagnetic fields.
AB  - The Draw-a-Bicycle Test is employed in neuropsychological testing of cognitive
      skills since the bicycle design is widely known and also because of its complex
      structure. The Draw-a-Bicycle Test has been administered routinely to patients
      with Parkinson's disease (PD) and other neurodegenerative disorders to evaluate
      the effect of transcranial applications of AC pulsed electromagnetic fields
      (EMFs) in the picotesla flux density on visuoconstructional skills. A seminal
      observation is reported in 5 medicated PD patients who demonstrated reversal of
      spontaneous drawing direction of the bicycle after they received a series of
      transcranial treatments with AC pulsed EMFs. In 3 patients reversal of the
      bicycle drawing direction was observed shortly after the administration of pulsed
      EMFs while in 2 patients these changes were observed within a time lag ranging
      from several weeks to months. All patients also demonstrated a dramatic clinical
      response to the administration of EMFs. These findings are intriguing because
      changes in drawing direction do not occur spontaneously in normal individuals as
      a result of relateralization of cognitive functions. This report suggests that
      administration of AC pulsed EMFs may induce in some PD patients changes in
      hemispheric dominance during processing of a visuoconstructional task and that
      these changes may be predictive of a particularly favourable response to AC
      pulsed EMFs therapy.

PMID- 9777445
TI  - Rain forest or mud field?

PMID- 9777446
TI  - The primordial mind and the work of the negative.
AB  - This paper was given at the celebration of Bion's centennial in 1997. At the
      request of the organisers of this conference, the work of Bion has been brought
      into perspective with the author's. The author has chosen to illumine Bion's
      concept of the primordial mind and considers the transformation of the beta
      elements into the alpha ones. He also refers to Bion's distinction of thoughts
      without thinker and thinking as needing thoughts to be thought by a thinker
      (thinking apparatus). The main point of the paper is Bion's opposition of
      'nothing' and 'no thing'. The author refers to Freud's paper on 'Negation'. He
      recalls his own model of the double limit. He tries to show how Freud's
      conception of representation has a much wider field than is usually stated. He
      emphasises differences between Freud's and Bion's 'basic assumptions'. After
      having tried to clarify Bion's ideas on 'O', 'K and -K', he recalls Bion's
      reference to Keats's negative capability. The author then gives a short account
      of his own concept of the 'work of the negative', finding correspondences with
      Bion's own concepts. As a conclusion two Indian myths are recalled for their
      great symbolic value.

PMID- 9777447
TI  - The non-verbal dimension in psychoanalysis: 'state' and its clinical
      vicissitudes.
AB  - The author focuses on state, a particular and continuing dimension of non-verbal
      expression which, though generally seen, heard or felt, often remains implicit.
      Basic, primal, reflecting psyche and soma woven together, state lies in a direct
      link with our earliest beginnings. Conveying one's affect, the sense of one's
      body--of one's self--in relationship to oneself and to the outer world, it
      influences and is influenced by the presence of the other. Thus, a change in
      state may be an early cue of the experiential effect of a perception, reflecting
      the impact of another's felt participation--including that other's state--the
      place from which we may truly find ourselves as participant-observers. State
      illuminates our unceasing subjectivity. In its subtle manifestation, it offers an
      added 'royal road' to what is yet unconscious, opening vital pathways of psychic
      experience that might otherwise have remained unnoted. Brought to collaborative
      and explicit focus, state can be mutually observed, and enquiry as to its meaning
      undertaken. It can be verbalised, and it can be analysed. Further, in sharpening
      our observance of nuances of data, attention to state will deepen consideration
      of the nature of our analytic evidence. Clinical examples are offered in
      elaboration of these ideas.

PMID- 9777448
TI  - Some considerations in the structure of the self and its pathology.
AB  - The author's intention is to contribute to the study of the structure of the
      self, both discussing the different processes of interiorisation and
      identification that play their parts in this development, and looking into the
      role played by the objects, and especially the superego. Interiorisation (the
      choice of this word is explained) is seen as a broad concept that covers
      incorporation, internalisation, introjection and introjective identification, and
      the dynamic of each of these mechanisms is discussed, along with its influence in
      the development of the structure of the self and of its constituent elements.
      Taking these concepts as a theoretical base, the author goes on to consider the
      field of 'pathology of defect' compared with the more classical pathology of
      conflict. Starting from the findings of different authors, especially Fairbairn
      and Kohut, he enlarges upon theoretical aspects of this 'pathology of defect' and
      its close relationship with Kohut's theories of narcissism, emphasising that,
      apart from other factors, an essential element in understanding this pathology is
      the development of the superego. Clinical material is presented to illustrate the
      theory.

PMID- 9777449
TI  - Some Jungian and Freudian perspectives on the Oedipus myth and beyond.
AB  - The authors traces some of the differences and similarities between those
      psychoanalysts and analytical psychologists who met in London to discuss
      contemporary attitudes to the oedipal situation. The conference provided an
      opportunity to consider briefly whether the characterisation of Jung as an
      apostate was correct or whether this was a consequence of the political need,
      following the separation of Jung and Freud, to protect psychoanalysis from
      professional criticism until it had become sufficiently well-established to be
      able to tolerate dissenting opinion. The author considers the misjudgements of
      history, why psychoanalysts do not read Jung, and some of the differences between
      the conceptual foundations of psychoanalysis and those of analytical psychology.
      After setting out some of the directions in which Jungian thought has been
      moving, particularly in respect of the work of Fordham, Klein and Bion, the
      author compares current clinical approaches as exemplified by established
      practitioners and includes parts of the discussion between members of the two
      associations. A brief indication of what the papers contained is also included.

PMID- 9777450
TI  - A cat as fetish: a contribution to the theory of fetishism.
AB  - Since Freud's original study of fetishism and his description of the genesis of
      the symptom, many additions and elaborations have been made to those
      propositions. In the past decade, fetishism has been increasingly applied to a
      wide variety of behavior and mentation, some with no overt sexual component. In
      this paper, the author, drawing on his observations made during a very lengthy
      analysis of a female patient, underscores the need to broaden the applicability
      of the diagnosis of fetishism but sees value in limiting it to the sexual
      situation. He suggests that a fetish does not need to be an inanimate object and
      expresses agreement with those who feel that fetishism is not limited to males.
      Additionally, he offers for consideration the idea that fetishism belongs on a
      continuum with a whole gamut of phenomena such as the need for a transitional
      object, the use of amulets, and the endowment of magical properties to words,
      ideas, rituals and objects. All these phenomena have in common the use of an
      outside object bestowed by magic and illusion to control anxiety. The
      hierarchical level of such anxiety and its ideational content (oedipal versus pre
      oedipal) are of less causative value than the ego's inability to master it
      without resorting to an outside object.

PMID- 9777451
TI  - Should we or shouldn't we? Some aspects of the confidentiality of clinical
      reporting and dossier access.
AB  - In this paper, reservations are expressed about two deviations from analytic
      neutrality: when the analyst seeks the patient's permission for publication or
      presentation of clinical material and when the analyst allows the patient access
      to the dossier under access-of-information legislation. In the first case,
      concern centres mainly on the entanglement of the patient in the therapist's
      sanctioned version of their work, an entanglement that might inhibit future
      revisions of the patient's self-understanding. In the second case, the analytic
      mental space, symbolised by the dossier, is viewed as neither uniquely the
      analyst's nor the patient's, a complex dialectical chamber the privacy of which
      must be respected, even by the patient whose discourse contributes to it, in
      order for it to function effectively. Transparency and accountability in the
      analytic context reveal a paradox that is not exclusive to it: the possibility of
      full disclosure runs counter to the expression of subjective truth. In a clinical
      example, curiosity about the dossier is seen to have been a new version of an
      earlier thwarted questioning about origins and identity. A specific deficiency in
      the therapist's understanding may have contributed to the patient's enactment.

PMID- 9777452
TI  - What is 'applied' in 'applied' psychoanalysis?
AB  - The 'application' of psychoanalytic concepts and methods to the products of
      culture has occupied a somewhat ambiguous position, seen by some as a secondary,
      derivative, even dubious procedure, by others as a valuable and legitimate
      extrapolation of the basic principles. This paper argues that such 'applications'
      were integral to the early development of the field and that, indeed, many of
      Freud's basic ideas were derived from non-clinical (i.e. cultural) sources. The
      continuing impact of cultural forces on clinical concepts can be seen in the
      recent reformulations of our views on the psychology of women. Psychoanalysis is
      to be seen, therefore, as a constantly evolving system of propositions and
      hypotheses that are capable of 'application' and study in both clinical and extra
      clinical settings. It is further argued that the continued development--even
      survival--of psychoanalysis requires the integration of its institutions and
      training facilities into the university system, permitting the free exchange of
      ideas across disciplines and a flexible educational structure that will encourage
      much-needed training in research as well as clinical methods. A brief
      illustration of the value of a psychoanalytic approach to the understanding of a
      specific work of art (Man Ray's painting 'Les Amoureux') is provided.

PMID- 9777453
TI  - 'Killing the angel in the house': creativity, femininity and aggression.
AB  - The author brings to bear an art historical perspective on the psychoanalytic
      understanding of creativity as an object relationship, proposing that the
      creative endeavour is determined by a wider, more complex network of internal and
      external object relationships than is usually assumed. The workings of tradition,
      language, contemporary practices, methods and materials are explored. Creative
      block is considered in the context of the determining relationships, with
      particular reference to the role of aggression. The position of the latter within
      psychoanalytic theories of creativity is surveyed and it is proposed that
      aggression has a pivotal place not primarily in instituting sublimation,
      reparation or reaction formation but simply because the processes of creativity
      demand it. Virginia Woolf's image of 'Killing the Angel in the House' is analysed
      and used to track the implications of gender, focusing on the concept of the
      muse. It is pointed out that traditionally, the fear, guilt and anxiety
      associated with aggressive creativity has been mediated by the muse, which is
      compared to the internal good object. Drawing on art history, artists'
      statements, and clinical material, the author illustrates the disparate means by
      which the presence of 'muse' can be internalised to infuse the relationships that
      constitute creativity.

PMID- 9777454
TI  - The monster within: Mary Shelley's Frankenstein and a patient's fears of
      childbirth and mothering.
AB  - This paper explores the fantasy, widespread among women, of giving birth to a
      monster, particularly a psychological monster. The author hypothesises two
      central intrapsychic issues underlying these fears: monsters are viewed as
      'incest babies' or as reflections of maternal aggression--evil, destructive parts
      of the mother passed on to the infant. Shame about femaleness is postulated as a
      third factor in the fear of producing something monstrous. Mary Shelley's novel,
      'Frankenstein', is an iconic literary representation of these themes. The author
      presents and discusses some psychobiographical material about Mary Shelley,
      speculating on her motives for writing this novel and tracing the intrapsychic
      concerns about incest and aggression as reflected in the novel itself. Some
      recent feminist and psychoanalytic critical readings of 'Frankenstein' are
      referenced as they reflect on the novel's concern with themes of female sexuality
      and procreation. Clinical material from the author's own practice is presented to
      illustrate these fears, so similar to those with which Mary Shelley was dealing.
      A discussion, citing some relevant literature, follows.

PMID- 9777455
TI  - The psychoanalytic interpretation of sexuality.

PMID- 9777456
TI  - The analyst's sexuality and the analytic process.

PMID- 9777458
TI  - Attachment representations in adult years: implications for psychoanalysis.

PMID- 9777459
TI  - Sexuality, sublimation and psychic activity.

PMID- 9777457
TI  - Manifestations of sexuality in child analysis.

PMID- 9777460
TI  - Homosexuality.

PMID- 9777461
TI  - Beyond poetry, music.

PMID- 9777462
TI  - Bioengineering in the millennium.
AB  - This symposium identified the major challenges in biomedical research that will
      benefit from bioengineering applications. Attention was focused on the important
      role that bioengineers will play in future advances in biomedical research. There
      was considerable discussion about how to integrate bioengineering with biological
      research in meeting the challenges of the twenty-first century. Symposium
      presenters showcased the accomplishments of NIH-funded bioengineering researches
      and increased the visibility of bioengineering to NIH leaders, staff, and members
      of the intramural and extramural research community. Recommendations were also
      made for future NIH-funded research projects. Attention was also placed on how
      basic bioengineering research can lead to commercialization of new health care
      technology and therefore maintain the nation's leadership in this important area.
      New products, from biotechnology and novel devices for diagnosis and treatment,
      are marketed through interactions between universities, medical centers, small
      start-up firms, and larger, more established companies. In the United States the
      gross revenue of the bioengineering private sector industry involved in the
      manufacture of health care products already exceeds $40 billion. More then 750
      persons attended this bioengineering symposium. Over 110 scientific posters and
      exhibits relating to biology and medicine were presented. They provided a forum
      for showcasing NIH-funded bioengineering projects and fostered future
      collaboration among academic investigators, industry, and members of the small
      business community. The contributions of Pugwash bioengineer, Maciej Natecz, a
      member of the Polish Academy of Sciences, was recognized by the Conference
      Planning Committee. He was honored for his work in nuclear disarmament. Indian
      medical scientists should note that this symposium provided a framework for the
      development of technology in biomedical sciences during the Twenty-First Century.
      Major concentrations in interdisciplinary research should occur at all of the
      premier research institutions in India.

PMID- 9777463
TI  - Reduced protein adsorption on novel phospholipid polymers.
AB  - We have synthesized phospholipid polymers containing 2-methacryloyloxyethyl
      phosphorylcholine (MPC) units as novel blood compatible polymers and have
      evaluated their interactions with blood components. It was found that in the
      absence of anticoagulants, blood clotting was delayed and blood cell adhesion and
      activation were effectively prevented on the MPC copolymer surface. A little
      amount of protein adsorbed on the MPC copolymer from human plasma was compared
      with conventional polymers, and the amount was reduced with increasing MPC unit
      fraction. To clarify the reason for the little protein adsorption on the MPC
      copolymer, the water structure in the hydrated polymer was examined with
      attention to the free water fraction. Hydration of the polymers occurred when
      they were immersed in water. The thermal analysis of these hydrated polymers
      revealed that the free water fractions in the poly(MPC-co-n-butyl methacrylate
      (BMA)) and poly(MPC-co-n-dodecyl methacrylate) were significantly larger than
      those in the poly(2-hydroxyethyl methacrylate(HEMA)). The conformation of
      proteins adsorbed on poly(HEMA) changed considerably but that on poly(MPC-co-BMA)
      was almost the same as the native state. We concluded from these results that the
      proteins are hardly adsorbed and do not change their original conformation on the
      polymer surfaces which possess a high free water fraction such as phospholipid
      polymers.

PMID- 9777464
TI  - Activated charcoal microcapsules and their applications.
AB  - Activated charcoal, long known to the ancients as a substance of therapeutic
      value in a variety of maladies, has recently been "rediscovered" to be of great
      value in medical applications. Activated charcoal hemoperfusion is effective in
      blood purification for removal of various circulating toxic materials and waste
      metabolites, directly. However, particulate release and platelet adhesion prevent
      its continued clinical use. Polymeric coatings or microencapsulation of charcoal
      within polymers have improved their blood compatibility. Chitosan encapsulated
      activated charcoal (ACCB) beads have been extensively investigated in our group
      for the removal of various toxins such as urea, creatinine, uric acid, bilirubin,
      etc. This article highlights various methods of microencapsulation procedures of
      activated charcoal and the importance of this novel material for a variety of
      biomedical applications. Further, this review provides an insight to the future
      perspectives for using them in clinical practice.

PMID- 9777466
TI  - Microtox system, a new approach to the safety evaluation of medical devices.
AB  - Medical devices of both intra- and extra-corporeal applications may contain
      leachable toxicants that warrant routine testing using internationally
      recognized/practiced protocols. An in vitro Microtox system comprising a selected
      bioluminescence strain of bacteria-Photobacterium phosphorium which emits light
      as an end product of its respiration, is used to screen out toxicants from
      biomaterials/devices. A Microtox system was standardized and validated in our
      laboratory conditions. Our experiences with extract of pyrogenic cardiotomy
      reservoir, blood filter and systemically toxic (in mice) Barium methacrylate
      (monomer), and CIBA epoxy polymer materials established a positive correlation
      with Microtox system. Hence, the Microtox system gives adequate evidence as an
      alternative in vitro method to evaluate the toxicity of biomaterials and medical
      devices.

PMID- 9777465
TI  - Polyethylene glycol (PEG) modified bovine pericardium as a biomaterial: a
      comparative study on immunogenicity.
AB  - Bioprosthetic heart valves made from glutaraldehyde (GA)-fixed porcine aortic
      valves or bovine pericardium (BP) are having some advantages over mechanical
      valves. However, their durability is low due to the calcification and
      immunological rejection. Study on immunogenicity is an important part in
      understanding the biocompatibility of materials. Polyethylene glycol (PEG) on
      pericardium can control biodegradation and calcification. Also, PEG exhibits low
      immunogenicity. We have studied the complement activation potential and the
      contribution of complement factors (biologic factors) on the calcification of PEG
      grafted pericardium samples and compared with standard (control) glutaraldehyde
      treated pericardium samples. PEG-grafted BP activated using GA and carbodiimide
      (EDC) could be selected for further studies since complement activation and
      calcification observed on these samples has been relatively low.

PMID- 9777467
TI  - Word production: dissociation of two retrieval modes of semantic memory across
      time.
AB  - To identify components that contribute to word-fluency performance, 126 patients
      referred to a Memory Clinic for suspected cognitive impairment underwent a
      neuropsychological examination including the Controlled Oral Word Association
      test (FAS; Benton & Hamsher, 1976). The number of words produced in the FAS test
      during six consecutive 10-s periods followed a negatively accelerated curve
      approaching an asymptotic level after about 30 s. The 18 FAS variables (3 letters
      x 6 periods) were entered into an exploratory factor analysis resulting in two
      factors. One factor, linked to a semiautomatic and rapid retrieval from semantic
      memory, loaded on the initial phase of the FAS test. A second factor, linked to
      an effortful and slow retrieval from semantic memory, loaded on the later phase
      of the FAS test. Thus, two retrieval modes of semantic memory contribute
      differently to the initial and later part of the FAS test, which may have
      theoretical and practical implications.

PMID- 9777468
TI  - Evaluating neuropsychological impairment in chronic fatigue syndrome.
AB  - This study was designed to provide an estimate of the prevalence of
      neuropsychological impairment in chronic fatigue syndrome (CFS), to evaluate the
      concordance between impairment found on standardized tests and self-reported
      neuropsychological problems, and to study the relationship between
      neuropsychological functioning and fatigue severity and psychological processes.
      We adopted an individual approach to determine neuropsychological impairment as
      contrasted with the group-comparisons approach used in previous studies. Also,
      correction for premorbid functioning and confounders was done on an individual
      basis. The results show that a minority of participants were impaired in
      neuropsychological functioning. There was no relationship between
      neuropsychological impairment on standardized tests and self-reported memory and
      concentration problems. Neuropsychological functioning was not related to fatigue
      or depression. Slowed speed of information processing and motor speed were
      related to low levels of physical activity.

PMID- 9777469
TI  - Determinants of cognitive performance in systemic lupus erythematosus.
AB  - Patients with systemic lupus erythematosus (SLE) may have a variety of
      neuropsychiatric syndromes. Assessment of cognitive functioning for these
      patients is complicated by increased prevalence and disease severity among groups
      obtained lower scores on measures of cognitive functioning in normative national
      samples. Cognitive ability was quantified in a diverse cohort of patients with
      SLE and a demographically matched group of control participants. Hierarchical
      regression demonstrated a small increase (6%) in explained variation in cognitive
      functioning when presence of SLE was added to the equation derived from
      demographic variables. No significant interaction was found between race and
      disease. These results suggest that increased frequency of cognitive impairment
      in African Americans with SLE is due to the additive effects of psychosocial
      variables.

PMID- 9777470
TI  - Detection of incomplete effort on the Wechsler Adult Intelligence Scale-Revised:
      a cross-validation.
AB  - This study determined whether the Vocabulary-Digit Span difference score and
      discriminant function based on subtests of the Wechsler Adult Intelligence Scale
      Revised (WAIS-R) developed by Mittenberg et al. (1995) could differentiate
      patients with moderate and severe traumatic brain injuries (n = 50) from persons
      with financially compensable mild head injuries who were giving incomplete effort
      (n = 50). Employing modified cutoff scores, the discriminant function and
      Vocabulary-Digit Span difference score accurately classified 90% and 79% of the
      cases, respectively. Persons with traumatic brain injuries may produce WAIS-R
      subtest patterns that can be differentiated from individuals showing incomplete
      effort. These WAIS-R algorithms appear useful in making that distinction.

PMID- 9777471
TI  - Age-related hemispheric asymmetry in object discrimination.
AB  - Young and elderly observers judged whether two sequentially presented images in
      either the left or right visual field (LVF or RVF) were the same or different.
      The two objects depicted were always from the same entry-level category, but
      could differ only in viewpoint (a "same" trial--observers were instructed to
      ignore viewpoint changes) and/or in exemplar (a "different" trial). Young
      observers showed no difference in sensitivity across visual fields. Elderly
      observers were less sensitive overall than young observers, and were less
      sensitive to stimuli presented in the LVF-RH than in the RVF-LH. The results of
      this experiment support the hypothesis that one type of visual cognitive
      functioning declines with age faster in the right hemisphere than in the left
      hemisphere.

PMID- 9777472
TI  - Analysis of visuospatial errors in patients with Alzheimer's disease or
      Parkinson's disease.
AB  - Ska and colleagues (1990) reported that patients with possible or probable
      Alzheimer's Disease (AD) make characteristic errors on a measure of line
      orientation judgment. We examined errors of line orientation judgment in a sample
      of 31 patients with probable AD, 28 patients with idiopathic Parkinson's disease
      (PD), and 24 normal elderly controls (NC). Results indicated that, in comparison
      to NC participants, some error types were made more frequently by patients with
      PD and patients with AD. No error type, however, was specific to AD alone. in
      contrast, PD patients were more likely than AD or NC participants to make a
      specific error in oblique line judgment. This finding is discussed in the context
      of visuospatial analysis and selective attention in patients with PD.

PMID- 9777473
TI  - Mayo's older Americans normative studies: category fluency norms.
AB  - Age-adjusted normative data are presented for persons over age 55 years on a
      common measure of category fluency. Further adjustment for education is also
      provided. These data were obtained as part of a series of projects known
      collectively as Mayo's Older Americans Normative Studies (MOANS). The normative
      information provided here should prove useful for characterizing performance on
      the individual measure of category fluency. In addition, these data should
      promote greater accuracy in comparing category fluency scores with performance on
      any other measures with MOANS norms, including tests of letter fluency.
      Limitations and unique features of MOANS normative data are also discussed.

PMID- 9777474
TI  - Effects of coaching on detection of malingering on the California Verbal Learning
      Test.
AB  - The diagnostic accuracy of California Verbal Learning Test (CVLT) indices to
      detect malingered head injury was examined using a simulation paradigm that
      included naive malingerers, malingerers provided with information about head
      injury, and normal controls (N = 90). The application of diagnostic cutoff scores
      for Recognition Discriminability and Recognition Hits derived from populations of
      individuals with bona fide head injury and individuals suspected of malingering
      (Millis et al., 1995) proved highly sensitive and modestly specific in detecting
      feigned head injury among both simulation groups. Results of analyses of variance
      and logistic regression support previous findings that malingerers overestimate
      memory impairment associated with mild head injury; however, they indicate that
      exposure to a simple instructional set may render insensitive many indices of
      malingering. In contrast, indices based on more subtle principles of learning
      theory hold promise in the detection of malingering, even in the presence of an
      instructional set.

PMID- 9777475
TI  - Validation of the Warrington theory of visual processing and the Visual Object
      and Space Perception Battery.
AB  - Competing hypotheses regarding the nature of visual processing were examined
      using the performance of 111 healthy older persons on the Warrington and James
      (1990) Visual Object and Space Perception Battery (VOSP). Confirmatory factor
      analysis indicated that a two-factor model corresponding to the Warrington theory
      of object and space perception as discrete domains showed excellent congruence
      with the data, despite limitations in the VOSP space perception tests that may
      have resulted in underestimation of model fit. Moreover, compared to a
      unidimensional model of visual processing, the Warrington model demonstrated a
      superior fit to the data. These findings add to the bodies of evidence supporting
      a dissociation between object- and space-perception abilities and defining the
      construct validity of the VOSP battery.

PMID- 9777476
TI  - Demographic influences on free and cued selective reminding performance in older
      persons.
AB  - This study evaluated the influence of age, gender, race, and education on
      learning and memory in older persons. Free and Cued Selective Reminding (FCSR)
      was administered to a community-based sample of 216 Caucasian and 50 African
      American seniors as part of a larger medical and neuropsychological battery.
      Although age, education, and gender influenced FCSR performance, race did not.
      The study suggests that memory performance is not influenced by race and that
      race-adjustment may not be necessary in the norming of memory tests.

PMID- 9777477
TI  - Effects of olfactory stimulation on the vigilance performance of individuals with
      brain injury.
AB  - Observers with brain injury and control participants performed a vigilance task
      during which they received periodic whiffs of unscented air or air scented with
      peppermint. Under both fragrance conditions, controls reduced the frequency of
      commissive errors (false alarms) over the course of the vigil, an adaptive
      strategy given the low probability of signals employed (0.04). The false alarm
      rate of observers with brain injury increased precipitously toward the end of the
      vigil in the unscented air condition. However, exposure to the scent of
      peppermint rendered the false alarm scores of observers with brain injury similar
      to that of controls, a result which is consistent with evidence that olfactory
      stimulation activates brain areas vital for planning and judgment.

PMID- 9777478
TI  - Learning people's names following severe closed-head injury.
AB  - Although problems remembering people's names rank highly among the subjective
      complaints of patients with closed-head injuries, very few studies have examined
      their memory for people's names by objective measurements. An experiment is
      reported in which patients with severe closed-head injuries and normal controls
      learned the same set of words, either as names or as possessions, for unfamiliar
      faces. Name learning proved to be impaired in the patients. Patient recall of
      meaningless names and possessions which were described by nonwords was equally
      poor. The patients, but not the controls, recalled significantly fewer names than
      possessions if these items were described by concrete nouns. This last finding
      suggests that the patients' problems with learning people's names can not be
      fully explained by a general verbal learning impairment.

PMID- 9777479
TI  - Impact of pediatric traumatic brain injury on components of verbal memory.
AB  - This 3-month longitudinal study examined spared and impaired components of verbal
      learning and memory after pediatric traumatic brain injury (TBI), using the
      California Verbal Learning Test for Children. School-aged participants with
      severe or mild-to-moderate TBI were compared to traumatically injured control
      subjects without head trauma. Participants were initially evaluated approximately
      1 month post injury, and again 3 months later. At Times 1 and 2, participants
      with severe TBI displayed deficits in immediate recall, delayed recall, and
      recognition accuracy, consistent with a mild encoding deficit. In both
      evaluations, participants with mild-to-moderate TBI performed similarly to
      controls. On average, mild verbal encoding deficits appear to be associated with
      severe, but not mild-to-moderate, pediatric TBI in the first several months post
      injury.

PMID- 9777480
TI  - Quantitative evidence for neuroanatomic and neuropsychological markers in
      dementia of the Alzheimer's type.
AB  - Meta-analytic methods were used to determine the sensitivity of
      neuropsychological, structural, and physiological measures to temporal
      hippocampal system function in dementia of the Alzheimer's type. Effect sizes are
      reported for the California Verbal Learning Test, the Wechsler Memory Scale
      Revised, structural (i.e., magnetic resonance imaging [MRI]), and functional
      (i.e., positron emission tomography [PET], single photon emission computed
      tomography [SPECT]) neuroimaging methods. Overall, effect sizes from MRI studies
      are larger than those obtained from SPECT and PET, respectively, but not as large
      as those obtained from the neuropsychological measures. On the basis of this
      finding, the neuropsychological and gross pathologic similarities between
      Alzheimer's disease, other dementing conditions, and mixed dementias, warrants
      the coupling of neuropsychological evaluation for its sensitivity with
      neuroimaging visualization for its specificity in improving diagnostic and
      differential accuracy.

PMID- 9777481
TI  - Depression after traumatic brain injury as a function of Glasgow Outcome Score.
AB  - One hundred and five patients with traumatic brain injury (TBI) were assessed for
      depressive symptomatology at 6 months postinjury and 66 of those patients were
      examined again at 12 months postinjury. At 6 months, 42% of the patients with TBI
      and 20% of the Other Injury Control Group (OIC) were identified as depressed.
      Individuals with poor outcome (as measured by Glasgow Outcome Score [GOS]) had a
      higher frequency of depressive symptomatology than those with good GOS outcome.
      At 12 months, 36% of the patients with TBI and 28% of the OIC group were
      identified as depressed. At 12 months, there was no difference in terms of
      frequency of depressive symptomatology among patients with TBI with poor,
      moderate, or good outcome.

PMID- 9777482
TI  - Analysis of error types in the trial making test evidences an inhibitory deficit
      in dementia of the Alzheimer type.
AB  - Several studies have reported low performances of patients with dementia of the
      Alzheimer Type (DAT) on the Trial Making Test (TMT), however, these studies were
      not designed to identify specific operations underlying this impairment. To
      better understand the attentional disorder in DAT, we analyzed the performances
      of patients with DAT and matched elderly adults on the TMT, with a detailed
      analysis of error types. The analysis showed that 67% of patients' errors were
      related to an inhibitory deficit versus only 24% in normal elderly adults.
      Therefore, it was suggested that inefficient inhibitory mechanisms are
      responsible, to a large extent, for the poor TMT performance of patients with
      DAT, supporting the hypothesis of an inhibitory dysfunction in DAT.

PMID- 9777483
TI  - Validation of a new scoring system for the Weigl Color Form Sorting Test in a
      memory disorders clinic sample.
AB  - The Bristol Memory Disorders Clinic uses the Weigl Color Form Sorting Test (CFST)
      to appraise abstraction and the ability to shift set. The original scoring system
      for the CFST (Grewal & Haward, 1984), developed on the premise that sorting to
      form is more difficult than sorting to color, had no score for an individual able
      to sort to form and subsequently unable to shift to color with a cue. Clinical
      experience suggested that the performance of some individuals required such a
      score. A new scoring system was developed and validated in a memory-disorders
      clinic sample. The validation showed the new score to be necessary and gave
      support to the original premise that people with organic brain damage show a
      preference for sorting to color.

PMID- 9777484
TI  - Role of null hypothesis significance testing (NHST) in the design of
      neuropsychologic research.

PMID- 9777485
TI  - Medical genetic evaluation for the etiology of hearing loss in children.
AB  - The purpose of the medical genetic evaluation is to identify the etiology of the
      hearing loss. To do so requires a multidisciplinary team that includes the
      otolaryngologist, audiologist, medical geneticist, and radiologist. A number of
      tests and procedures are now available to assist in the search for the cause of
      hearing losses. The importance of sensitivity when providing genetic counseling
      is emphasized. Molecular genetics offers potential for continued progress in
      understanding the etiologies of hearing loss. Recent advances in this area are
      discussed.

PMID- 9777486
TI  - Single gene influences on radiologically-detectable malformations of the inner
      ear.
AB  - Inner ear malformations associated with hearing loss or vestibular dysfunction
      are discussed from the viewpoint of the etiologies of the malformation. Symptoms
      of classification of inner ear malformations are discussed. The significance of
      malformations of the cochlea and vestibular aqueduct to auditory function are
      discussed. Genetics features and characteristics of Branchio-oto-renal,
      Waardenburg's, Pendred's, DiGeorge's, Wildervanck, Fountain, and Treacher Collins
      syndromes are discussed in relation to ear abnormalities and hearing. Similar
      attention is given to genetic studies of nonsyndromic hearing loss.

PMID- 9777487
TI  - Branchio-oto-renal syndrome.
AB  - Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder with
      branchial, otologic, and renal manifestations. The branchial manifestations
      usually are inconsequential, however the hearing impairment and renal
      malformations can be significant. The disease is caused by mutations in the EYA1
      gene.

PMID- 9777488
TI  - Sensorineural hearing loss caused by mitochondrial DNA mutations: special
      reference to the A1555G mutation.
AB  - Mutations in mitochondrial DNA, which are maternally inherited, have been thought
      to be one of the causes of sensorineural hearing loss. Two mitochondrial
      mutational sites (A1555G, A7445G) have been reported to be responsible for non
      syndromic hearing impairments. The A1555G mutation causes increased
      susceptibility to aminoglycoside antibiotic-induced hearing loss as well as non
      syndromic sensorineural hearing loss. Our wide screening study showed that there
      may be a great number of subjects within the Japanese population who have the
      A1555G mutation. Recent reports suggest that high-risk populations may exist
      throughout the world. The aminoglycoside-induced hearing loss associated with a
      mitochondrial mutation is commonly bilateral, symmetric, high frequency involved,
      and is sometimes associated with progressive sensorineural hearing loss.

PMID- 9777489
TI  - Genetics and hearing loss: a review of Stickler syndrome.
AB  - Stickler syndrome is an autosomal dominant multisystem disease. The four most
      affected systems are craniofacial, skeletal, ocular, and auditory. The
      manifestations of Stickler syndrome vary considerably among affected individuals.
      Audiologists and speech-language pathologists should be familiar with the
      characteristics associated with Stickler syndrome to facilitate early
      identification and appropriate management.

PMID- 9777491
TI  - Identification and energetic ranking of possible docking sites for pterin on
      dihydrofolate reductase.
AB  - The reliability of new methodology for detecting sites for ligand binding on the
      surfaces of proteins has been tested using a range of dihydrofolate reductase
      (DHFR) crystal structures. Docking of the pterin molecule to ten such DHFR
      structures has been examined. Initial docking sites were selected using the VDW
      FFT method we have developed recently. This procedure was followed by rigid
      geometry optimization and solvation energy calculations using our parametrized
      reaction field multipoles (PRFM) method and the finite difference solution of the
      Poisson equation (FDPB) method. Two different sets of MM parameters, from the
      OPLS and Amber94 force fields, have been used. In eight cases the energy of the
      complexes with pterin bound at the active site was the lowest with the recent
      Amber94 parameters. In one case the spurious first-ranked site was only 1.8
      kcal/mol lower in energy compared with the active site. The other 'failure' of
      the method may, in fact, represent a valid initial binding site. The calculations
      with the old OPLS parameters gave slightly worse results.

PMID- 9777492
TI  - A branch-and-bound method for optimal atom-type assignment in de novo ligand
      design.
AB  - This paper investigates a computational procedure for the determination of the
      atom types on the vertices of a molecular skeleton to optimize interaction with
      the receptor site whilst maintaining a synthetically reasonable structure. The
      connectivity of the skeleton is analysed and appropriate atom types are compiled
      for each vertex. Receptor ionization and conformational states are generated by
      varying the positions of hydrogen atoms and electron lone pairs in the carboxyl,
      rotatable hydroxyl and amino groups. The structure is divided into small non
      overlapping substructures. Atom types are assigned exhaustively onto each of the
      substructures using a depth-first search method; chemical rules are applied to
      reject unacceptable atom combinations early on. An empirical interaction score is
      calculated and the representatives of each partial structure are stored in
      ascending order according to their scores. The branch-and-bound procedure is then
      used to find the structures with the lowest scores. The method is illustrated
      using five protein-ligand complexes.

PMID- 9777490
TI  - Prediction of binding constants of protein ligands: a fast method for the
      prioritization of hits obtained from de novo design or 3D database search
      programs.
AB  - A dataset of 82 protein-ligand complexes of known 3D structure and binding
      constant Ki was analysed to elucidate the important factors that determine the
      strength of protein-ligand interactions. The following parameters were
      investigated: the number and geometry of hydrogen bonds and ionic interactions
      between the protein and the ligand, the size of the lipophilic contact surface,
      the flexibility of the ligand, the electrostatic potential in the binding site,
      water molecules in the binding site, cavities along the protein-ligand interface
      and specific interactions between aromatic rings. Based on these parameters, a
      new empirical scoring function is presented that estimates the free energy of
      binding for a protein-ligand complex of known 3D structure. The function
      distinguishes between buried and solvent accessible hydrogen bonds. It tolerates
      deviations in the hydrogen bond geometry of up to 0.25 A in the length and up to
      30 degrees in the hydrogen bond angle without penalizing the score. The new
      energy function reproduces the binding constants (ranging from 3.7 x 10(-2) M to
      1 x 10(-14) M, corresponding to binding energies between -8 and -80 kJ/mol) of
      the dataset with a standard deviation of 7.3 kJ/mol corresponding to 1.3 orders
      of magnitude in binding affinity. The function can be evaluated very fast and is
      therefore also suitable for the application in a 3D database search or de novo
      ligand design program such as LUDI. The physical significance of the individual
      contributions is discussed.

PMID- 9777493
TI  - Modelling a 3D structure for EgDf1 from Echinococcus granulosus: putative
      epitopes, phosphorylation motifs and ligand.
AB  - EgDf1 is a developmentally regulated protein from the parasite Echinococcus
      granulosus related to a family of hydrophobic ligand binding proteins. This
      protein could play a crucial role during the parasite life cycle development
      since this organism is unable to synthetize most of their own lipids de novo.
      Furthermore, it has been shown that two related protein from other parasitic
      platyhelminths (Fh15 from Fasciola hepatica and Sm14 from Schistosoma mansoni)
      are able to confer protective inmunity against experimental infection in animal
      models. A three-dimensional structure would help establishing structure/function
      relationships on a knowledge based manner. 3D structures for EgDf1 protein were
      modelled by using myelin P2 (mP2) and intestine fatty acid binding protein (I
      FABP) as templates. Molecular dynamics techniques were used to validate the
      models. Template mP2 yielded the best 3D structure for EgDf1. Palmitic and oleic
      acids were docked inside EgDf1. The present theoretical results suggest definite
      location in the secondary structure of the epitopic regions, consensus
      phosphorylation motifs and oleic acid as a good ligand candidate to EgDf1. This
      protein might well be involved in the process of supplying hydrophobic
      metabolites for membrane biosynthesis and for signaling pathways.

PMID- 9777494
TI  - Toward the identification of the cardiac cGMP inhibited-phosphodiesterase
      catalytic site.
AB  - Cyclic nucleotide phosphodiesteras (PDEs) comprise a complex group of enzymes;
      five major PDE families or classes with distinctive properties have been
      identified. Among these a great deal of interest has recently been focused on the
      so called cGMP-inhibited low K(m) cAMP phosphodiesterase (cGI PDE) or PDE III. A
      number of positive inotropic agents, including the well-known milrinone, display
      a specific inhibition of PDE III as primary mechanism of action. Recent studies
      have been carried out to develop a pharmacophore model of the PDE III active
      site. We therefore performed molecular modelling and 3D-SAR studies so as to
      better define structural requirements for potent and selective enzymatic
      inhibition. The DISCO (DIStance COmparison) strategy has been applied on a set of
      compounds taken from literature and a milrinone analogue previously synthesized
      by us, all of which are characterized by a marked inotropic effect but with
      varying degrees of enzyme selectivity. A common pharmacophoric model was derived,
      validated and considered as starting point to perform a 3D-SAR study using the
      GRID force field and PCA (Principal Component Analysis) with the aim of
      rationally designing more selective inhibitors. This paper presents the results
      of this theoretical approach.

PMID- 9777496
TI  - Conformational energy penalties of protein-bound ligands.
AB  - The conformational energies required for ligands to adopt their bioactive
      conformations were calculated for 33 ligand-protein complexes including 28
      different ligands. In order to monitor the force field dependence of the results,
      two force fields, MM3* and AMBER*, were employed for the calculations.
      Conformational analyses were performed in vacuo and in aqueous solution by using
      the generalized Born/solvent accessible surface (GB/SA) solvation model. The
      protein-bound conformations were relaxed by using flat-bottomed Cartesian
      constraints. For about 70% of the ligand-protein complexes studied, the
      conformational energies of the bioactive conformations were calculated to be < or
      = 3 kcal/mol. It is demonstrated that the aqueous conformational ensemble for the
      unbound ligand must be used as a reference state in this type of calculations.
      The calculations for the ligand-protein complexes with conformational energy
      penalties of the ligand calculated to be larger than 3 kcal/mol suffer from
      uncertainties in the interpretation of the experimental data or limitations of
      the computational methods. For example, in the case of long-chain flexible
      ligands (e.g. fatty acids), it is demonstrated that several conformations may be
      found which are very similar to the conformation determined by X-ray
      crystallography and which display significantly lower conformational energy
      penalties for binding than obtained by using the experimental conformation. For
      strongly polar molecules, e.g. amino acids, the results indicate that further
      developments of the force fields and of the dielectric continuum solvation model
      are required for reliable calculations on the conformational properties of this
      type of compounds.

PMID- 9777495
TI  - Tautomeric equilibria in 8-oxopurines: implications for mutagenicity.
AB  - Free-radical-induced DNA damage by ionizing radiation leads to a number of
      oxidized purines, of which 7H-8-oxoguanine (8OG) and 7H-8-oxoadenine (8OA) are
      predominant and known to cause an appreciable amount of cellular damage. A
      detailed quantum mechanical study at various levels of theory in both the gas
      phase and in an aqueous solution has been carried out in order to assess the
      tautomeric preferences of the bases. The calculated energies of various plausible
      tautomers suggest that at higher levels of ab initio theory with inclusion of
      electron correlation, the 8-keto-6-enolic form of 8-oxoguanine (8OG2) would
      predominate over the 6,8-diketo form (8OG1) in the gas phase whereas the 6-amino
      8-keto form (8OA1) predominates over the other possible tautomers of 8
      oxoadenine. Aqueous solvation, however, changes the gas-phase order for 8
      oxoguanine, 8OG1 turning out to be the major tautomeric species in an aqueous
      medium. The estimated free energies of hydration by polarized continuum models
      are indicative that the mutagenically significant amounts of minor tautomeric
      forms of 8-oxoguanine and 8-oxoadenine exist in the aqueous phase and might be
      held responsible for inducing transversional as well as transitional mutations.

PMID- 9777497
TI  - Comparative molecular field analysis of artemisinin derivatives: ab initio versus
      semiempirical optimized structures.
AB  - Based on the belief that structural optimization methods, producing structures
      more closely to the experimental ones, should give better, i.e. more relevant,
      steric fields and hence more predictive CoMFA models, comparative molecular field
      analyses of artemisinin derivatives were performed based on semiempirical AM1 and
      HF/3-21G optimized geometries. Using these optimized geometries, the CoMFA
      results derived from the HF/3-21G method are found to be usually but not
      drastically better than those from AM1. Additional calculations were performed to
      investigate the electrostatic field difference using the Gasteiger and Marsili
      charges, the electrostatic potential fit charges at the AM1 level, and the
      natural population analysis charges at the HF/3-21G level of theory. For the HF/3
      21G optimized structures no difference in predictability was observed, whereas
      for AM1 optimized structures such differences were found. Interestingly, if ionic
      compounds are omitted, differences between the various HF/3-21G optimized
      structure models using these electrostatic fields were found.

PMID- 9777498
TI  - Seven years clinical experience with mandibular distraction in children.
AB  - Mandibular distraction was performed on 14 children, between September 1991 and
      December 1997. Their average age was 6.9 years, ranging from 1.5 to 13.5 years.
      All patients had severe hypoplastic mandibles with retromandibulism. Seven of the
      children (50%) had respiratory distress due to obstruction of the upper airway
      before distraction. This resolved in every case. Five patients underwent
      unilateral and nine bilateral distraction. A total of 23 distractors were used,
      15 were applied extraorally and 8 endorally. The average latency time after
      operation was 2.8 days, but for the past 2 years, distraction was started
      beginning with the operation. The distraction was increased twice daily for an
      average of 5.5 weeks, by 0.4 or 0.5 mm each time, depending on the distractor.
      Computed tomography and ultrasound were used to follow the ossification process
      in the distraction gap and to measure the lengthening achieved. Subsequent
      retention time averaged 2.4 weeks. The mandibles were elongated by up to 18 mm
      (average 9.3 mm) and the respiratory distress symptoms resolved in all patients.
      Several minor complications which are reported occurred. Six patients were
      followed up for periods between 3 and 7 years. During this time further growth of
      the distracted mandibles was recorded.

PMID- 9777499
TI  - The role of latency in mandibular osteodistraction.
AB  - Even though osteodistraction has been well established in the extremities, the
      parameters used in craniofacial distraction have been essentially borrowed from
      orthopaedic experience. Latency is widely practised but its relevance has not
      been fully investigated. The purpose of this study was to establish the role of
      latency in mandibular distraction osteogenesis. Twenty-two growing Wethers sheep
      were allocated to four experimental groups. Six animals were allocated to each of
      Groups A, B and C and underwent bilateral mandibular corticotomies and attachment
      of an external lengthening device. Latent periods of 0, 4 and 7 days respectively
      were observed prior to beginning distraction. The distraction protocol consisted
      of a rate of 0.5 mm twice daily for 20 days, followed by a consolidation phase of
      20 days after which the sheep were killed. Histology, bone densitometry and 3
      point mechanical testing were performed on the harvested mandibles. Group D
      formed the control group (n = 4). Histologically, the distracted bone exhibited
      bone formation primarily via intramembranous ossification with scattered islands
      of cartilage. The regenerated bone had mechanical properties significantly weaker
      than the undistracted control group (P < 0.05), but between the experimental
      groups no statistically significant differences were demonstrable either in
      mechanical strength or DEXA density. These data indicate that a change in latency
      does not alter the properties of the regenerated bone in mandibular distraction
      osteogenesis and indeed no latent interval may be necessary at all in
      craniofacial distraction. This has implications for the duration of device
      fixation in distraction procedures.

PMID- 9777501
TI  - Microsurgical treatment of midfacial tumours involving the skull base.
AB  - Various approaches to the base of the skull for the treatment of cranial base
      tumours are described in detail. Advantages and disadvantages of the particular
      approaches are discussed. This clinical experience is based on 303 neoplasms
      involving the base of the skull, operated on by the authors. Retrospective
      survival studies are presented and a review of the literature on the subject is
      discussed. Utilizing microsurgical techniques the 2-, 3- and 5-year survival
      rates were significantly improved. The functional and aesthetic outcomes were
      also dramatically superior compared with standard ablative procedures.
      Reconstructive postoperative strategies are suggested.

PMID- 9777500
TI  - Preoperative planning and intraoperative navigation in skull base surgery.
AB  - Experience with the commercially available, 3-D navigation systems Viewing Wand
      (ISG, Mississauga, Ontario, Canada) and SPOCS (Aesculap, Germany) in skull base
      surgery is presented. Having meanwhile been tested in over 60 clinical trials,
      the systems achieved an accuracy of < or = 2.7 mm which, at the moment, we deem
      sufficiently acceptable to proceed with their clinical evaluation. There was no
      difference in intraoperative accuracy between the mechanical and the optical
      navigation systems. The systems proved to be very helpful in identifying the
      extent of the tumours and in visualizing the proximity of vital structures. 3-D
      planning, simulation and intraoperative navigation especially facilitates surgery
      in anatomically complicated situations, without risk of damaging neighbouring
      structures. The SPOCS (Surgical Planning and Orientation Computer System)
      revealed a considerably improved flexibility in handling and a better integration
      into the surgical procedure in comparison with the relatively inflexible and
      space-demanding Viewing Wand arm. Especially, the 'offset' function of the SPOCS
      offers the possibility of a virtual elongation of the instrument and thus, in
      combination with the on-line visualization of the corresponding images, of a
      'look ahead' operation. By using computer-assisted simulation and navigation
      systems, we can expect quality improvement and risk reduction. More extensive and
      radical interventions seem possible.

PMID- 9777502
TI  - Frontal sinus fractures: principles of treatment and long-term results after
      sinus obliteration with the use of lyophilized cartilage.
AB  - The most commonly used techniques for frontal sinus obliteration involve the
      implantation of an autogenous tissue graft: either fat, muscle or bone.
      Lyophilized allogenic cartilage due to its unique properties, such as the
      tendency to ossification and resistance to volume reduction, can be used as the
      material of choice for sinus obliteration. A clinical and radiological study of
      66 patients operated on for frontal sinus fractures, between January 1 1988
      through December 31 1995 was undertaken. Variables recorded included the
      aetiological factors, the clinical and radiological fracture features with the
      corresponding treatment modality, the association of frontal sinus fractures with
      intracranial involvement, the early and late postsurgical complications and the
      correlation between pre- and postoperative radiological findings. Obliteration of
      the frontal sinus with lyophilized cartilage chips was performed in 51 (77.3%)
      patients. The postsurgical evaluation showed no major complications. Revision of
      the frontal sinus was only required in one patient. The radiological findings
      verified the progressive calcification of the obliterated sinus. Allogenic
      lyophilized cartilage implantation offers distinct advantages in cases of severe
      frontal sinus trauma: 1. There is nearly unlimited availability of the material.
      2. There is no need for a second operation field with the associated potential
      donor site morbidity. 3. The operation time is reduced due to the avoidance of a
      second operation on the donor site.

PMID- 9777503
TI  - Relevance of SCC-Ag, CEA, CA 19.9 and CA 125 for diagnosis and follow-up in oral
      cancer.
AB  - The prognosis of oral cavity carcinoma is limited by recurrent disease or lymph
      node metastasis. Secondary to surgery and radiotherapy, anatomical structures are
      often severely changed and make early diagnosis of renewed tumour growth by
      clinical and radiological examination difficult. We studied the course of serum
      SCC-Ag, CEA, CA 19.9 and CA 125 in 121 patients with untreated squamous cell
      carcinoma of the head and neck (SCCHN) before and after therapy and evaluated
      their relevance for diagnosis and follow-up in oral cancer. CA 19.9 and CA 125
      seemed to be useless for this tumour entity. CEA resembled more the alcohol
      consumption and smoking habits of the patients examined than their state of
      disease. Only SCC-Ag correlated with the tumour burden and represented the
      disease course. In the event of relapse, half the patients had an exponential
      increase in SCC-Ag, 1-2 months prior to diagnosis.

PMID- 9777505
TI  - Complications after microsurgical tissue transfer in the head and neck region.
AB  - In recent years, the use of microsurgically re-anastomosed free transplants has
      become a proven technique for the reconstruction of defects in the head and neck
      region, which is demanding from both aesthetic and functional points of view. A
      retrospective catamnestic study on 227 free tissue transfers in the Department
      for Oral and Maxillofacial Surgery at the University of Tubingen showed good
      healing with relatively low failure rates of the transplants used. A significant
      proportion of local complications, arising postoperatively, was to some degree
      due to pre-existing medical conditions, tumour-specific pretreatments and the
      particular wound-healing situation found in head and neck interventions. The
      highest relative rate of complications at the site of origin was seen amongst
      osteomuscular transplants (20%) whilst (fascio) cutaneous and visceral
      transplants were found to result in a low percentage of problems (4%). In
      contrast, the healing of iliac crest transplants was accompanied by various local
      complications in 12% of the cases, slightly higher than 20% amongst (fascio)
      cutaneous and abdominal transplants and well above 30% for latissimusdorsi and
      scapular transplants. General complications, in particular of a respiratory
      and/or psychiatric nature, were found in 23% of the patients.

PMID- 9777504
TI  - Comparison of two types of arterialized venous forearm flaps for oral
      reconstruction and proposal of a reliable procedure.
AB  - The mechanism of survival of venous flaps is not yet completely understood. To
      determine the conditions for reliable success, in 1996 and 1997 we used
      arterialized venous forearm flaps for oral reconstruction in patients with
      neoplastic disease. Building on earlier experience with flow-through flaps, we
      compared two different designs obeying the following specifications: five so
      called arterialized flow-through flaps, elevated from the ulnar flexor side of
      the forearm, with a single vein for orthograde inflow and outflow, diameter not
      larger than 2 mm (type 1); and five arterialized flaps with two parallel veins on
      the proximal side of the flap, also with a diameter of 1-2 mm, to avoid by
      passing of flap tissue by 'catching' the blood in the venous/capillary system
      (type 2). There were nine male and one female patients with a mean age of 55.7
      years. We covered defects of the anterior or anterolateral floor of the mouth to
      avoid folding of the flaps. Microsurgical anastomosis was done to the facial
      artery, the cranial thyroid artery and the external jugular vein or the facial
      vein. Average size of the flaps was 23 +/- 7.28 cm2 (type 1) and 25 +/- 5 cm2
      (type 2). Four flaps of type 1 showed total or subtotal success and only one was
      lost because of a haematoma. In comparison with this we saw three losses in type
      2 and only one partial and one total success, respectively. Analysis showed
      regularly occurring problems: there was failure of venous drainage in the lost
      type 2 flaps one day after microsurgery. In the flow-through flaps and the
      surviving type 2 flaps which had visible communicating branches between the two
      veins, the partial by-passing of the arterial input avoided this problem. There
      was no donor site morbidity after covering with a split-thickness skin graft. It
      could be shown that survival of arterialized venous forearm flaps is based on a
      combination of an arteriovenous shunt and capillary blood flow. In conclusion, we
      define six rules for a reliable venous forearm flap.

PMID- 9777506
TI  - Open bite deformity in amelogenesis imperfecta. Part 1: An analysis of
      contributory factors and implications for treatment.
AB  - Anterior open bite (AOB) is often seen in patients with amelogenesis imperfecta
      (AI). The skeletal and dental components were analysed in 15 patients with AI and
      AOB. Measurements on cephalometric radiographs and dental models were compared
      with those of 130 patients with AOB but without enamel anomalies. Skeletal
      components in the AI and non-AI group were comparable. The AI group showed omega
      shaped dental arches and a reversed mandibular curve of Spee. Orthodontic
      treatment options are limited because of the conical form of the teeth, tight
      contacts in the posterior regions and the condition of enamel resulting in
      difficulties in bonding brackets. Fixation problems encountered during surgery
      are discussed. A multidisciplinary treatment is outlined consisting of a multi
      segment Le Fort I osteotomy followed by prosthetic rehabilitation to stabilize
      occlusion for at least one year postoperatively.

PMID- 9777507
TI  - A clinical study on oroantral fistulae.
AB  - The report presented is an analysis of 98 patients with an oroantral fistula
      (OAF). The tooth most frequently involved was the upper second molar, followed by
      the first molar. The highest incidence was seen in the fourth and third decades
      of life and the lowest incidence in the second decade. In this study,
      intercurrent sinusitis was the most obvious cause of the chronic oroantral
      communication. The closure of OAF is one of the more challenging problems in oral
      surgery. Long-term successful closure of OAF depends on the technique used, the
      size and location of the defect, and on the presence or absence of sinus disease.
      Among the several techniques proposed for treatment of OAFs, in the majority of
      cases, the buccal advancement flap technique was used in this study. The
      advantages and limitations of the technique are discussed.

PMID- 9777508
TI  - Consensus and debate in the definition of breeding objectives.
AB  - The breeding objective is usually to increase the profit of the firm, industry,
      or society that is investing in a breeding program. This objective should include
      long-term genetic gain and nonadditive genetic changes such as inbreeding
      depression and possibly a weighting against the variability of outcome. The
      breeding objective is described by a profit function that takes genetic values as
      input and produces profit as outcome. This profit function may be a bioeconomic
      model of the farm. The traits in the profit function should relate as directly as
      possible to all sources of income and costs. The profit function can include
      variables controlled by management decisions if these interact with genetic
      merit. The differences between genotypes should be evaluated when management
      variables are optimized for each genotype. In the long term, mean profit is
      expected to be close to zero, and all costs are assumed to be variable costs.
      Under these conditions, the relative economic weights are the same, regardless of
      how the farm is constrained how the unit for which profit is calculated, whether
      the perspective is that of individual producers, an industry, or consumers.
      However, if price signals are not passed along the chain from consumers to seed
      stock breeders, the economic weights become distorted. The use to which breeding
      objectives are put, the perspective from which they are calculated, the rescaling
      and biological versus economic objectives, and the special problems associated
      with the inclusion of length of herdlife in the objective are discussed.

PMID- 9777509
TI  - Applying breeding objectives to dairy cattle improvement.
AB  - Otherwise well-researched definitions of breeding objectives and selection
      criteria may never be used in practice if those definitions do not take into
      account the perceptions and wishes of the breeders for whom they are designed.
      Finding selection criteria that are widely accepted and implemented is a daunting
      task that requires considerable time and full interaction between the scientists
      and the industry. We review various aspects of this process and, in particular,
      how scientific principles can be used to ensure that the outcome best meets both
      the perceptions and needs of the users while remaining as close as possible to
      the technical economic optimum. Alternative methods of presenting and delivering
      selection indexes, such as index expression, index formulation, focus on response
      to selection rather than on index weights, construction of component indexes, and
      the use of direct accounting for costs of constraints rather than rescaling
      methods can all help in improving acceptance of an index. Development and
      implementation of selection criteria also involve consideration of the selective
      mating decisions that form an integral part of selection decisions in the field.
      The technical basis of factors that foster emphasis on individual mating
      decisions in the field are discussed in relation to formulation of the breeding
      goal and selection index and in relation to nonlinear economic and genetic
      parameters. Strategies that focus on use of a linear index for the selection of
      sires and dams followed by selective mating of selected parents have the greatest
      potential for implementation in the industry. We focus on examples taken from the
      Canadian dairy industry, but principles apply generally.

PMID- 9777510
TI  - Objectives and strategies in pig improvement: an applied perspective.
AB  - Largely because of the influence of Charles Smith, simple performance testing of
      pigs over the previous 30 yr has been highly successful. With larger production
      units, current genetic objectives can be divided into two components: 1) to raise
      genetic potential for production traits and 2) to maximize the probability that
      this potential can be realized in practice. Faster improvement through increased
      accuracy and a more flexible nucleus structure are offered by BLUP methodology.
      Electronic measures of feed intake permit selection based on feeding behavior and
      the shape of the feed intake curve. After the elimination of the halothane gene,
      the next limiting factor for meat quality could be intramuscular fat. With more
      than 1500 mapped genes, the main constraints on marker-assisted selection are the
      high costs of DNA testing and the relatively small effects of this selection on
      performance. A combination of the possible effects of BLUP, the Meishan breed,
      and the ESR gene could give genetic improvements totaling 4 liveborn piglets per
      litter over the next 10 yr. There appear to be no limits on future improvement of
      lean growth, but risks are adverse changes in reproduction and disease
      resistance. Existing quantitative methods of improvement are very cost effective.
      The greatest challenge for molecular technologies may be the genetics of the
      immune system.

PMID- 9777511
TI  - Optimizing pure line breeding strategies utilizing reproductive technologies.
AB  - The development of new reproductive techniques has had a great effect on schemes
      for dairy cattle improvement; AI resulted in progeny-testing schemes, and, more
      recently, multiple ovulation and embryo transfer has resulted in nucleus breeding
      schemes. In traditional breeding schemes, the use of multiple ovulation and
      embryo transfer resulted in only small increases of genetic gains because the
      selection intensity of bull dams was already high, but the selection intensity of
      cows in nucleus breeding schemes increased considerably. This increase makes
      nucleus schemes very competitive, especially when in vitro maturation and
      fertilization is used to increase female reproductive rates further. The
      increased genetic gain results in the selection of young females (i.e., optimal
      generation intervals are shortened). The combined effect of multiple ovulation
      and embryo transfer and shorter generation intervals increases the rate of gain
      by approximately 15% but also increases the rate of inbreeding and variances of
      the selection response (i.e., the risk of the breeding scheme) by about 80%.
      Recently, selection methods have been developed to reduce the rates of inbreeding
      or the variance of the selection response in breeding schemes. A scheme that
      maximized the selection differential while constraining the rate of inbreeding
      yielded about 30 to 60% more selection response than selection for BLUP estimated
      breeding value at the same rate of inbreeding. For the future, the combination of
      juvenile predictors of genetic merit (e.g., DNA markers) and techniques that
      further increase female reproductive rates seem very promising methods to
      increase the rates of genetic gain. As an example, the genetic gain of an
      optimized hybrid nucleus scheme could be increased 24% by the combined use of
      juvenile predictors and in vitro maturation and fertilization. Fertilization of
      fetal embryos was predicted to increase rates of gain by up to 18%.

PMID- 9777512
TI  - Mate selection by groups.
AB  - The two key components in a breeding program can be described as the development
      of an objective function and the implementation of an algorithm for mate
      selection to target the objective function. However, mate selection is
      unacceptably slow for objective functions that involve longer term aims, such as
      engineering a good connection between herds. This paper proposes animal
      clustering to facilitate group mate selection, plus a step to refine mate
      selection for individual animals. Cluster analysis is used to form groups of
      animals within each sex based on nominated factors such as breed, herd, age, and
      EBV. Mate selection is then performed on groups, reducing the size of the problem
      considerably. The example used involved a three-breed crossbred population with a
      simple objective function to maximize predicted progeny merit. Twenty sires and
      500 dams were to be selected from 816 and 1784 candidates. Group mate selection
      achieved 96.9% efficiency (random selection, 0%; full mate selection, 100%) and
      took 0.28 s to compute (394.2 s for full mate selection). Permitting more
      candidates to reach the individual mate selection stage increased efficiency to,
      for example, 98.9% at the cost of an extra 1.15 s. Efficiency was also improved
      by permitting more clusters.

PMID- 9777513
TI  - Detection and utilization of single genes without DNA assays.
AB  - Quantitative traits are often assumed to be controlled by a large number of loci
      that each have a small effect. Under this assumption, the distribution of
      genotypic and phenotypic values can be adequately modeled by a multivariate
      normal distribution. Thus, most genetic analyses are based on mixed linear
      models. Evidence is accumulating, however, for the presence of loci that have
      large effects on traits of economic importance. If the genotypes for such loci
      can be observed without error, then--conditional on these observed genotypes-
      genotypic and phenotypic values follow a multivariate normal distribution, and
      data from very large pedigrees can be analyzed using a mixed linear model that
      includes the genotypic effects for these loci as fixed effects. However, when the
      major genotype is not observed, the genotypic and phenotypic values follow a
      mixture of multivariate normal distributions, and analyses based on fitting a
      mixed linear model may not be optimum, especially for populations undergoing
      selection and nonrandom mating. Several approaches are discussed for the genetic
      analysis of data when the major genotypes are not known.

PMID- 9777514
TI  - Restricted maximum likelihood analysis of linkage between genetic markers and
      quantitative trait loci for a granddaughter design.
AB  - A REML for the estimation of location and variance of a single quantitative trait
      locus, together with polygenic and residual variance, is described for the
      analysis of a granddaughter design. The method is based on a mixed linear model
      that includes the allelic effects of the quantitative trait locus, which are
      assumed to be normally distributed. Information from four marker loci situated on
      a single chromosome was available to derive the covariances at the linked
      quantitative trait locus. A derivative-free algorithm is described that makes use
      of the specific structure of the granddaughter design. The procedure has been
      applied to simulated data for a granddaughter design with 50 grandsire families
      of 40 sires each. Error variance was 60, and total additive genetic variance
      equaled 40; the quantitative trait locus explained either 10 or 25% of the latter
      variance. The size of the marker bracket containing the quantitative trait locus
      was either 10 or 30 cM. The power of detecting the quantitative trait locus
      ranged from 19 to 99%. Estimates of total genetic variance and variance explained
      by the quantitative trait locus were found to be empirically unbiased. A small
      bias was found in location estimates, especially when markers were not fully
      informative. The accuracy of parameter estimates was greatly improved by the use
      of information from individual daughters.

PMID- 9777515
TI  - Strategies to utilize marker-quantitative trait loci associations.
AB  - Marker-assisted selection holds promise because genetic markers provide
      completely heritable traits than can be measured at any age in either sex and
      that are potentially correlated with traits of economic value. Theoretical and
      simulation studies show that the advantage of using marker-assisted selection can
      be substantial, particularly when marker information is used, because normal
      selection is less effective, for example, for sex-limited or carcass traits.
      Assessment of the available information and its most effective use is difficult,
      but approaches such as crossvalidation may help in this respect. Marker systems
      are now becoming available that allow the high density of markers required for
      close associations between marker loci and trait loci. Emerging technologies
      could allow large numbers of polymorphic sites to be identified, practically
      guaranteeing that markers will be available that are in complete association with
      any trait locus. Identifying which polymorphism out of many that is associated
      with any trait will remain problematic, but multiple-locus disequilibrium
      measures may allow performance to be associated with unique marker haplotypes.
      This type of approach, combined with cheap and high density markers, could allow
      a move from selection based on a combination of "infinitesimal" effects plus
      individual loci to effective total genomic selection. In such a unified model,
      each region of the genome would be given its appropriate weight in a breeding
      program. However, the collection of good quality trait information will remain
      central to the use of these technologies for the foreseeable future.

PMID- 9777516
TI  - Risk factors for Clostridium difficile infection.
AB  - A systematic review of the literature to identify risk factors associated with
      Clostridium difficile infection was conducted. Two main outcomes were considered:
      C. difficile diarrhoea and C. difficile carriage. A qualitative assessment, based
      on a set of defined and consistently applied criteria, appeared to be the best
      approach for risk factors other than antibiotic use, as an approach based on meta
      analysis would have utilized only the information provided by a minority of the
      studies. Risk factors for which there was evidence suggestive or consistent with
      an association with C. difficile diarrhoea were: increasing age (excluding
      infancy), severity of underlying diseases, non-surgical gastrointestinal
      procedures, presence of a nasogastric tube, anti-ulcer medications, stay on ITU,
      duration of hospital stay, duration of antibiotic course, administration of
      multiple antibiotics. For malignant haematological disorders there was evidence
      of an association only with C. difficile carriage, but there were no suitable
      studies to explore a possible association of this risk factor with symptomatic
      infection. Antibiotic use lent itself to quantitative assessment with meta
      analysis using logistic regression. Exposure to an antibiotic was shown to be
      statistically significantly associated with both C. difficile diarrhoea and C.
      difficile carriage. The meta-analysis approach enabled the ranking of individual
      antibiotics in relation to the risk of C. difficile infection, though the 95%
      confidence intervals were often wide and overlapping. Antibiotics associated with
      a lower risk of C. difficile diarrhoea should be considered, especially when
      attempting to control a C. difficile outbreak or when prescribing for a patient
      with other C. difficile risk factors. This systematic review of the literature
      enabled the identification of features it would be desirable to consider in
      future epidemiological studies.

PMID- 9777517
TI  - Antibiotic resistance among clinically important gram-positive bacteria in the
      UK.
AB  - The resistance of bacteria to antibiotics, particularly those used for first-line
      therapy, is an increasing cause for concern. In the UK, the prevalence of
      resistance to methicillin and mupirocin in Staphylococcus aureus, and to
      penicillin and macrolides in Streptococcus pneumoniae, appear to be increasing.
      There has also been an increase in the number of hospitals where glycopeptide
      resistant enterococci are known to have been isolated. The increases in
      methicillin-resistant S. aureus and glycopeptide-resistant enterococci are due,
      in part, to the inter-hospital spread of epidemic strains. Although new
      quinolones and streptogramins with activity against Gram-positive bacteria
      (including strains resistant to currently available agents) are under
      development, there is no reason to believe that resistance to these agents will
      not emerge. The control of resistance in Gram-positive bacteria will require a
      multi-faceted approach, including continued and improved surveillance, a
      reduction in the unnecessary use of antibiotics, and the application of other
      strategies such as vaccination.

PMID- 9777518
TI  - The prognostic factors of adult gram-negative bacillary meningitis.
AB  - Seventy-seven patients with Gram-negative bacillary meningitis (GNBM), 57 males
      and 20 females, aged 17-86 years, were identified at Kaohsiung Chang Gung
      Memorial Hospital, over an 11-year period. Fifty-four infections were community
      acquired, and 23 were nosocomial; 49 were spontaneous and 28 occurred after head
      surgery or neurosurgery. The organisms most frequently involved were Klebsiella
      pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and Acinetobacter. Rarer
      pathogens included Citrobacter species, Serratia marcescens, Enterobacter
      cloacae, and Proteus mirabilis. All patients who did not receive appropriate
      antibiotic therapy died. The mortality in those treated with appropriate
      antibiotics was 28%. Other statistically significant prognostic factors included
      septic shock, initial level of consciousness, hyperosmolar hyperglycemic
      nonketotic coma, disseminated intravascular coagulation, high cerebrospinal fluid
      lactate levels and leucocytosis. In the multiple logistic regression analysis,
      only appropriate antimicrobial therapy and septic shock were strongly associated
      with mortality even after adjusting for other potentially confounding factors.
      Despite the high mortality, management can be improved by early diagnosis, early
      use of appropriate antibiotics, and correction of underlying and associated
      medical derangement.

PMID- 9777519
TI  - Positive intravenous line tip cultures as predictors of bacteraemia.
AB  - Intravenous line tip cultures provide valuable information when taken in
      conjunction with blood culture, but in practice are often performed in isolation.
      This retrospective study has evaluated: (1) the frequency of isolated line tip
      culture; and (2) whether the species of microorganism isolated from line tip
      culture, using the Maki semi-quantitative culture method, is predictive of
      bacteraemia. Of 2753 line tip culture episodes in 1659 patients between May 1993
      and August 1995, 2230 were performed in isolation (81%). Evaluation of 792
      positive line tip culture episodes in 654 patients where blood cultures were
      performed in the period from 48 h before, to 24 h after tip culture, identified
      825 line tip isolates. Of these, 194 were associated with a blood culture
      positive for the same species. The rate of positive blood culture, according to
      species, ranged from 10-72%. The highest rate was seen for methicillin
      susceptible Staphylococcus aureus where 70 of 97 line tip episodes (72%) were
      associated with positive blood culture. This compared with a rate of 17% for
      coagulase-negative staphylococci (P < 0.0001). Patients with line tip cultures
      positive for S. aureus should be considered to be at high risk of bacteraemia.

PMID- 9777520
TI  - Analysis and impact of infectious disease consultations in a general hospital.
AB  - During an 18-month period, data from all patients in whose care our infectious
      diseases (ID) service was involved, were recorded in a computerized database. A
      total of 4184 new consultations was recorded. The consultations were solicited by
      the patients' physicians in 3326 cases (80%) and initiated by the ID service in
      the remainder. The purpose of the consultations was diagnosis (14%), therapy
      (39%), both diagnosis and therapy (40%), and prophylaxis (6%). Two thousand and
      ninety-four consultations (50%) were performed at the bedside, and the others by
      personal or telephone discussion. ID consultation was given in more than 10% of
      admitted patients in six departments, 46% of the admissions in the ICU, and
      6.9/100 hospitalized patients. Recommendations included: antibiotic manipulation
      (i.e., initiation, change or discontinuation of antibiotic treatment) (51%);
      performance of tests (13%); performance of diagnostic or therapeutic procedures
      (5%); prophylaxis (4%) or no change in management (26%). Analysis of the
      solicited vs unsolicited consultations and of the bedside vs telephone
      consultations revealed that sub-groups of consultations differ significantly from
      each other in many aspects. Recording of consultations enables the ID service to
      evaluate its activity and to direct efforts to departments with high rates of
      infectious diseases and/or antimicrobial usage.

PMID- 9777521
TI  - Quality of perioperative antibiotic administration by French anaesthetists.
AB  - Antibiotics are the most prescribed drugs in hospitals in France and
      approximately one-third of prescriptions are for antimicrobial prophylaxis.
      Although the principles of prophylaxis have been defined over the years, there is
      still widespread misuse of antimicrobials for that purpose. The aim of this
      survey was to determine whether prescription of prophylactic antibiotics by
      French anaesthetists complies with the French Guidelines on Surgical Antibiotic
      Prophylaxis. Information was sought concerning the agent(s) recommended, the
      timing of the first dose and the duration of prescription. A total of 1473 French
      anaesthetists was studied. For the great majority (93%), the first antibiotic
      dose is administered at time of induction of anaesthesia, as recommended by the
      guidelines. First- and second-generation cephalosporins are frequently selected,
      as well as co-amoxiclav. In contrast to the guidelines, third-generation
      cephalosporins (3GCs) are widely prescribed in digestive and urological surgery
      and quinolones in urological surgery. Duration of prescription is limited to 48 h
      by most anaesthetists (94%), however there is a strong tendency to prescribe
      prophylaxis for longer periods in the immunocompromised and patients undergoing
      major surgery. This survey indicates discrepancies between the French Guidelines
      on Surgical Antibiotic Prophylaxis and the current practice of French
      anaesthetists. Major concerns are the use of antibiotics such as 3GCs or
      fluoroquinolones and prescription for periods exceeding 48 h. In conclusion,
      compliance with guidelines for prophylactic antimicrobial administration should
      be more strict in surgical patients.

PMID- 9777522
TI  - Unnecessary hospital infection control practices in Thailand: a survey.
AB  - The high prevalence of hospital-acquired infection has a significant impact on
      the operating cost of hospitals in Thailand. A nationwide questionnaire survey
      was conducted to determine how frequently unnecessary infection control
      procedures were performed. Nearly 17% of hospitals routinely cleaned floors with
      disinfectants; 48% installed ultraviolet lights in the operating room; 57%
      performed routine environmental cultures; 68% reported fogging of the operating
      theatres and the isolation rooms; wearing a protective gown in the intensive care
      units was routine in 57% of the surveyed hospitals; 30% of hospital laundries set
      temperatures unnecessarily high and sterile gloves were overused in 25% of
      hospitals. Large cost reduction can be achieved by discontinuing these practices.

PMID- 9777523
TI  - Investigation of gaseous ozone for MRSA decontamination of hospital side-rooms.
AB  - A domestic, gaseous ozone generator was investigated for use in the
      decontamination of hospital side-rooms that have housed patients colonized with
      methicillin-resistant Staphylococcus aureus (MRSA). Three models of bacterial
      contamination were used. These were exposed to ozone generation in a standard
      hospital side-room for 4 and 7 h. A methicillin-sensitive and a methicillin
      resistant strain of S. aureus were compared. Ozone concentrations of 0.14 ppm
      were reached, levels which are sufficient to cause mild pulmonary toxicity.
      Bacterial counts were reduced in the vicinity of the gas generator in most
      instances, but the effect elsewhere in the room was, at best, limited. MRSA
      appeared more resistant to the effects of ozone than methicillin-sensitive S.
      aureus. We conclude that the device tested would be inadequate for the
      decontamination of such hospital side-rooms.

PMID- 9777524
TI  - A rapid (20 h) solid screening medium for detecting methicillin-resistant
      Staphylococcus aureus.
AB  - Methicillin aztreonam mannitol salt agar is a sensitive and reliable solid
      screening medium for detecting methicillin-resistant Staphylococcus aureus
      (MRSA). With this medium an incubation period of only 20 h is sufficient to
      either produce visible colonies of MRSA or to exclude MRSA (no staphylococcal
      colonies). Coagulase testing (requiring a further 6 h) enables coagulase-positive
      isolates to be provisionally reported as 'possible MRSA' 26-30 h after the swabs
      were collected. The medium supports growth of intrinsically resistant
      staphylococci including low-expression-class MRSA (methicillin minimum inhibitory
      concentration (MIC) 8-16 mg/L), but methicillin susceptible staphylococci and
      beta-lactamase hyperproducers are suppressed.

PMID- 9777525
TI  - Ultrasound instruments as possible vectors of staphylococcal infection.
AB  - In this study, we evaluated whether ultrasound instruments are important in the
      spread of nosocomial staphylococcal infections. Following genomic typing by
      pulsed-field gel electrophoresis, it was apparent that ultrasound procedures
      transferred colonizing staphylococci from a patient's skin to the ultrasound
      instruments. Staphylococcus aureus survived in the transmission medium for longer
      than in water. Furthermore, S. aureus was more resistant to the ultrasonic medium
      than Pseudomonas aeruginosa, also a significant cause of hospital-acquired
      infections. To prevent staphylococcal transmission by ultrasound equipment, we
      recommend disinfection of the probe and removal of the medium after each
      examination.

PMID- 9777526
TI  - Contamination of wounds by direct inoculation in total hip arthroplasty: a
      prospective clinical study.

PMID- 9777527
TI  - Typhoid fever mimicking nosocomial infection.

PMID- 9777528
TI  - The nose: an underestimated source of Staphylococcus aureus causing wound
      infection.
AB  - For the last fifty years, the nose has been intermittently recognized and
      targeted as a source of Staphylococcus aureus causing surgical site infection. In
      London in 1959, Williams and co-workers established for the first time that nasal
      carriers had increased rates of surgical sepsis compared with non-carriers. For
      half of these patients, the source was the patient's own nose. Post-admission
      acquisition of tetracycline-resistant strains was associated with even higher
      rates of infection. The increasing appearance of epidemic methicillin-resistant
      S. aureus (MRSA) in the 1980s rekindled interest in these (largely overlooked)
      studies, when the elimination of nasal carriage by topical mupirocin proved
      pivotal for the control of MRSA in Northern Europe and elsewhere. In the late
      1980s and 1990s, Boelaert, Holton and others, appreciating the work performed
      forty years previously, used nasal mupirocin for the successful prevention of
      sepsis with S. aureus in patients on haemodialysis and continuous ambulatory
      peritoneal dialysis without incurring problems with mupirocin resistance. In
      1995, Kluytmans and colleagues demonstrated that nasal carriage of S. aureus is a
      significant risk factor for wound infection after cardiac surgery. Towards the
      year 2000, the use of prophylactic nasal mupirocin for the prevention of serious
      sepsis in major clean surgery is emerging as a plausible and exciting new
      strategy.

PMID- 9777529
TI  - Reduction of Staphylococcus aureus nasal carriage and infection in dialysis
      patients.
AB  - Numerous studies conducted in different countries and in different populations of
      patients on dialysis have consistently documented that a large proportion of such
      patients carry Staphylococcus aureus in their nares and that the risk of them
      becoming infected with their own strains is quite high. Furthermore, S. aureus
      infections can cause considerable morbidity and mortality in these patients.
      Thus, decolonization of the nares may prevent S. aureus infections and the
      attendant complications. The published data that support the use of rifampicin,
      intranasal mupirocin and povidone-iodine to prevent S. aureus infections in
      patients on dialysis are reviewed in detail.

PMID- 9777530
TI  - Reduction of surgical site infections in major surgery by elimination of nasal
      carriage of Staphylococcus aureus.
AB  - Staphylococcus aureus has long been recognized as an important pathogen in human
      disease. Staphylococcal infections occur regularly in hospital patients and,
      despite antibiotic therapy, have severe consequences. An increasing number of
      such infections are caused by methicillin-resistant S. aureus (MRSA) strains,
      many of which have become multi-resistant to treatment. In an unblinded
      intervention trial, with historical controls, perioperative nasal carriage of S.
      aureus was eliminated using mupirocin nasal ointment. A significant reduction in
      surgical site infection was observed post-intervention in the treated group of
      patients. No resistant to mupirocin was observed. The results of this study
      warrant a prospective randomized, placebo-controlled study to confirm the
      efficacy of mupirocin.

PMID- 9777531
TI  - Eradication of nasal carriage of Staphylococcus aureus--is it cost-effective?
AB  - In cardiothoracic surgery, the costs of surgical-site infection (SSI) arise from
      additional postoperative procedures (approximately US $5000 per patient) and
      prolonged hospital stay (approximately $11,500 per patient). Application of nasal
      mupirocin reduced SSIs by 63% compared with historical controls. This would have
      resulted in savings provided that the attributable cost of an SSI was more than
      $245. Mupirocin was estimated to reduce the risk of bacteraemia in haemodialysis
      patients by 84% compared with historical controls. A model using data on Medicare
      payments for haemodialysis admissions was used to estimate the impact on hospital
      costs. The conclusion was that mupirocin would have been cost-saving but the
      model did not provide sufficient detail about hospital costing to allow
      assessment of its relevance in other settings. In a prospective, randomized,
      placebo-controlled trial in continuous ambulatory peritoneal dialysis (CAPD)
      patients, mupirocin reduced the risk of staphylococcal exit-site infection (ESI)
      from 0.42 to 0.14 per patient-year. However, as in a previous comparison with
      historical controls, there was an increase in the rates of ESIs caused by Gram
      negative bacteria in patients who received mupirocin, bringing the rate of total
      ESIs up to that observed in the placebo group. There was some evidence that
      infections caused by Gram-negative bacteria had less severe consequences than
      staphylococcal infections. It is concluded that application of nasal mupirocin to
      nasal carriers of Staphylococcus aureus may be cost-saving in patients undergoing
      cardiac surgery or haemodialysis but, if the analysis is restricted to the cost
      of management of ESIs, it may not be cost-saving in CAPD. However, reducing the
      risk of staphylococcal ESI may reduce the risk of catheter loss and subsequent
      transfer to haemodialysis and this merits further study.

PMID- 9777532
TI  - New strategies for the use of mupirocin for the prevention of serious infection.
AB  - Nasal mupirocin has an important role to play in the prevention of Staphylococcus
      aureus infection by eliminating nasal carriage of this organism. Indeed, in many
      countries nasal mupirocin is one of the mainstays for controlling outbreaks of
      methicillin-resistant S. aureus. Eradication of nasal S. aureus with mupirocin
      has been shown to be effective in preventing postoperative infections in patients
      undergoing cardiothoracic surgery and in preventing exit-site infections in
      patients undergoing haemodialysis. It has been proposed that the use of mupirocin
      should be extended to other situations, such as the prevention of postoperative
      infections in patients undergoing implant surgery and the prevention of
      bacteraemias in high-risk patients. Clinical trials are needed to establish the
      efficacy of mupirocin in these situations. Both low-level and high-level
      resistance have been reported during treatment with nasal mupirocin. Low-level
      resistance does not represent a significant clinical problem but high-level
      resistance resulting from indiscriminate use may give grounds for concern.
      Further review of these issues is required. As with any antibiotic, mupirocin
      should be used judiciously, as part of an integrated programme of infection
      control.

PMID- 9777533
TI  - Influence of mite growth culture phases on the biological standardization of
      allergenic extracts.
AB  - House dust mites are a well known cause of asthma and other respiratory
      allergies. In order to improve the standardization of allergenic extracts for
      diagnosis and immunotherapy, it is important to determine the frequency and
      concentration of the components, both the major and the minor allergens during
      the growth period of the mite population. In a previous paper we demonstrated
      that the laboratory cultures of Dermatophagoides pteronyssinus and
      Dermatophogoides farinae exhibited three well differentiated growth phases:
      latency, exponential growth, and death of the culture. Biological standardization
      of extracts from the two mite species were carried out by skin prick tests in a
      group of 20 patients, using different concentrations of the extracts at the three
      growth phases. The patient sera were also studied by means of the RAST technique
      to determine the levels of specific IgE for each phase. The extracts produced
      from the exponential growth phase of the cultures revealed six times more
      relative allergenic activity in in vivo studies, and average RAST values were
      approximately three times higher than those extracts from latency and death
      phases. The reproducibility of the extract production method was assessed by
      comparing different batches obtained in similar conditions. The results showed
      batch-to-batch homogeneity allergenic activity. In conclusion, it was
      demonstrated that extracts obtained from cultures with the highest concentration
      of live mites (maximum growth phase) render the best diagnostic results in vivo
      and in vitro.

PMID- 9777534
TI  - Determinations of Par j 1 by a competitive enzyme immunoassay using human
      specific IgE and IgG. Validation by skin prick testing.
AB  - Par j 1 is the major allergen of Parietaria judaica. The objectives of this study
      were the following: 1) to purify Par j 1; 2) to develop an enzyme immunoassay
      based on the bivalent properties of specific IgE and IgG to determine the Par j 1
      content in several batches of P. judaica extracts; and, 3) to study the
      contribution of Par j 1 to the total allergenicity and antigenicity of P. judaica
      extracts. P. judaica pollen was extracted and subjected to hydrophobic
      interaction and gel filtration chromatography for the purification of Par j 1.
      Inhibition enzyme immunoassays, SDS-PAGE and immunoblotting were used to
      characterize the allergen content. The in vivo biological potency of the extracts
      was estimated by skin prick testing 26 P. judaica clinically sensitive patients.
      The new enzyme immunoassay showed a high degree of specificity and sensitivity,
      detecting from 2 to 100 ng Par j 1/ml. The range of Par j 1 content in nine
      batches ranged from 23% to 78% of the total protein in the extracts. The Par j 1
      content showed a significant correlation with the allergenic potency of these
      extracts evaluated by specific IgE inhibition and skin prick testing; the
      correlation with the specific IgG inhibition capacity was not significant.
      Purified Par j 1 shows great specific IgE and IgG binding capacity; its content
      can be determined using this newly developed enzyme immunoassay. Par j 1 levels
      exhibit a significant correlation with the biological potency of the extracts.
      This method allows the detection of Par j 1 isoforms.

PMID- 9777535
TI  - Characterization of allergenic fractions from Drechslera monoceras.
AB  - Drechslera monoceras, a fungus of the Deuteromycota phylum, is fairly frequent in
      Brazil, and is spread through the atmosphere. In previous studies done in the
      city of Sao Paulo, it was found that in relation to 42 other fungi extracts, the
      crude extract of this fungi demonstrated a more intense cutaneous reaction in
      patients with respiratory allergies. Biochemical, antigenic and allergenic
      evaluations were carried out at various growth stages of this fungus. Based on
      these facts, the purpose of this research was the fractionation and allergenic
      characterization of the allergenic extract of D. monoceras to be used in
      diagnosis and immunotherapy in patients with positive cutaneous reaction to this
      fungus. In the city of Sao Paulo, 13 of 248 patients with respiratory allergy
      (asthma and/or rhinitis) showed positive reaction following cutaneous tests (skin
      prick tests). The crude extract of D. monoceras was fractionated by SDS-PAGE. The
      visible fractions were then separated by electroelution to be inoculated into
      BALB/c mice to evaluate the production of IgE antibody. The IgE content was
      detected by passive cutaneous anaphylaxis test in Wistar rats, and two fractions
      of approximate molecular weights of 14.4 and 36 KDa reacted to the test. The in
      vitro allergenic characterization was carried out by Western blotting, and three
      fractions of approximate molecular weights of 14.4, 36 and 60 KDa were positive.
      It was concluded that the extract of D. monoceras has at least three allergenic
      determinants, which can be used for diagnosis and immunotherapy in patients with
      respiratory allergy to this fungi.

PMID- 9777536
TI  - Hypersensitivity to chironomid larvae.
AB  - Chironomid larvae (red midge larvae) are often used by aquarists as fish food.
      Their hemoglobins can cause IgE-mediated allergic diseases in exposed and
      unexposed people. The aim of this study was to find out the prevalence of
      positive skin tests to chironomids in patients suffering from rhinitis and/or
      bronchial asthma in Ciudad Real (Spain). A total of 465 patients were submitted
      to skin prick tests with chironomids in addition to common inhalant allergens.
      The patients with positive skin prick test (wheal > or = 3 mm) to these larvae
      answered a questionnaire. Skin prick tests with Acarus siro, shrimp, cockroach
      and mosquito (Culex pipiens) were carried out. Serum levels of total IgE and anti
      Chironommus thummi, anti-Dermatophagoides pteronyssinus, anti-shrimp, and anti
      mosquito (Aedes communis) IgE were determined. Conjunctival or nasal provocation
      tests were carried out with chironomids. Of the 465 patients skin tested, 19
      showed a positive skin prick test with chironomids, corresponding to 4.1% of all
      patients and 6% of the atopic patients. None were monosensitized. Significant
      correlations were found between skin prick test results with chironomids and
      mites (p < 0.005). Of the 19 patients, 15 had positive skin prick test with the
      common mosquito C. pipiens. Seven patients showed elevated anti-D. pteronyssinus
      IgE, six elevated anti-shrimp IgE, and 10 showed elevated anti-A. communis IgE.
      Provocation tests with chironomids were positive in 14 patients (four nasal and
      10 conjunctival tests). Conjunctival provocation tests were carried out in 16
      controls and were positive in three; all three showed positive skin prick test
      with chironomids. One patient had occupational allergy from the larvae
      (aquarist). After mosquito bites, five patients showed immediate wheal reactions
      and one patient suffered an anaphylactic reaction after several mosquito bites.
      Only two patients remembered having been in contact with chironomids as fish
      food. We found hypersensitivity to these larvae in patients without apparent
      contact to them. These patients could have become sensitized in various ways,
      including: 1) inhaling particles of chironomids or others that are cross-reactive
      with them; 2) exposure to products used as fish food containing chironomids; and,
      3) through cross-reactivity with other allergens such as mites, shrimp or
      mosquitoes.

PMID- 9777537
TI  - The allergen spectrum in Turkey and the relationships between allergens and age,
      sex, birth month, birthplace, blood groups and family history of atopy.
AB  - This study was performed retrospectively on 2,342 patients who were treated in
      the allergy department from 1985 to 1996. All patients had been skin prick tested
      with 40 common aeroallergens in Turkey. Allergen immunotherapy was given to 1,455
      of them. Mean age of the patients was 25.9 (range 5 to 69). Fifty-five percent
      were males and 45.1% females. Forty percent had bronchial asthma and 60.2% had
      allergic rhinitis. Fifty-five percent of them had a family history of atopy.
      Sensitization to pollens was 59.7%, to house dust 20.5%, to molds 2%, to pollens
      and molds 2.9%, to pollens and house dust 11.5%, to molds and house dust 1.4%,
      and to pollens, molds and house dust 2%. The grass pollen sensitivity was
      threefold more common than that for trees, and fourfold more common than that for
      weed pollens. The diagnosis of bronchial asthma in the 5 to 9 age group was
      higher than in the other age groups (p < 0.005). The mold sensitization increased
      in parallel with age and it was the highest in 60 to 69 age group (p < 0.0001).
      There was no relationship between the allergens and sex, history of family atopy
      or blood group (p > 0.05) (except for house dust allergen). However, there was a
      relationship between month of birth (p < 0.005, p < 0.05, respectively) and
      birthplace (p < 0.001) with pollen and house dust allergen. House dust and molds
      were more common causes of bronchial asthma than pollens (p < 0.001, p < 0.01,
      respectively). In conclusion, the most common allergen was pollen in Turkey. In
      addition, atopic diseases are multifactorial, including such factors as genes and
      environment. Month and place of birth may influence early exposure and subsequent
      risk for allergy.

PMID- 9777538
TI  - DNase I hypersensitive sites in human I epsilon region of immunoglobulin heavy
      chain genes abnormally induced by interleukin-4 in B-lymphocytes of atopic
      patients with high levels of serum IgE.
AB  - Interleukin-4 (IL-4) induces germline C epsilon transcripts prior to C epsilon
      switch recombination in human B-lymphocytes. In chromatin, nucleosome-free
      regions known as nuclease hypersensitive sites represent the "open windows" that
      allow enhanced access of crucial resident cis-acting DNA sequences to transacting
      factors. In this study, lymphoblastoid cell lines (LCLs) were established from
      surface IgE negative B-cells of healthy children and patients with high levels of
      serum IgE, using Epstein-Barr virus. The germline C epsilon transcript was
      amplified from cDNA of the patients' LCLs cultured with low concentrations of
      recombinant interleukin-4 (rIL-4, 10 IU/ml), while it was not amplified from the
      cDNA of the healthy LCLs with the low concentration of rIL-4. The germline C
      epsilon transcript was strongly amplified from cDNA of the patients' LCLs with
      high concentrations of rIL-4 (100 IU/ml), compared with that of the healthy LCLs
      with the high concentrations of rIL-4. Moreover, the DNase I hypersensitive site
      of the I epsilon region was abnormally induced in the patients' LCLs even by a
      low concentration of rIL-4, compared with that of healthy LCLs. Our results
      indicate that DNase I hypersensitive sites in the I epsilon region of
      immunoglobulin-heavy chain genes are abnormally induced by IL-4 in the B-cells of
      atopic patients with high levels of serum IgE, and, as a result, the germline C
      epsilon transcript is abnormally expressed.

PMID- 9777539
TI  - SC5b-9 is the most sensitive marker in assessing disease activity in Brazilian
      SLE patients.
AB  - This study investigated whether increased plasma levels of terminal complement
      complex (SC5b-9) or split products correlate with disease activity and clinical
      manifestations in Brazilian systemic lupus erythematosus (SLE) patients.
      Comparisons with conventional measurements of complement and other inflammatory
      markers were also performed. Plasma levels of SC5b-9, C3a desArg, C1rs
      C1Inhibitor, C3b(Bb)P, C3, C4, erythrocyte sedimentation rate (ESR) and
      mucoproteins (MP) were measured in 41 patients with SLE of different disease
      activity: 10 patients with none, 15 patients with mild, and 16 patients with
      moderate or severe activity. All parameters, with the exception of C3 and
      C3b(Bb)P, showed a statistically significant correlation with disease activity.
      Plasma levels of SC5b-9, C3a desArg, C4, CH50, ESR and MP revealed significant
      differences between the groups of patients without activity and those with
      moderate or severe disease. Although none of the variables were able to
      discriminate between patients without and those with mild activity, SC5b-9, C3a
      desArg, C4, ESR and mucoproteins showed significant differences between the
      patients with mild and those with moderate or severe disease. Among all the
      variables, SC5b-9 levels showed the most significant results and correlated well
      with the severity of the disease (p < 0.0005). Our data suggest that elevated
      levels of complement activation products, particularly of SC5b-9 are more
      sensitive markers in assessing disease activity than conventional laboratory
      diagnosis. Modern complement diagnosis is therefore recommended for monitoring
      disease progress in SLE patients.

PMID- 9777541
TI  - Delayed reaction to cow's milk proteins: a case study.
AB  - Allergy to cow's milk proteins has been defined as any adverse reaction mediated
      by immunological mechanisms to one or several of these proteins. The diagnosis
      can be made based on clinical manifestations supported by immune activation of in
      vitro parameters. Reactions to cow's milk have been classified according on their
      onset as immediate (< 45 min) or delayed-type (from 2 h to days). We describe a
      patient with late respiratory manifestations after milk intake, probably due to
      more than one immunological mechanism. He was an 18-year-old male who since
      infancy had presented serous rhinorrea, sneezing, nasal blockade, oropharyngeal
      pruritus and occasional dyspnea 12 to 48 h after ingestion of milk and its
      derivates. We performed skin prick and intradermal tests with whole milk and
      fractions. Patch tests were also carried out with whole milk purchased at a
      supermarket and with the extracts described, in their original form and
      vehiculized in vaseline. Total and serum specific IgE and IgG4 to milk fractions,
      histamine release test (HRT) to milk fractions, and precipitating antibodies by
      contraimmunoelectrophoresis against milk fractions were also measured. As a
      control we repeated this test in a patient with IgE-mediated manifestations to
      milk proteins and in two healthy controls. We performed a single-blind placebo
      controlled challenge with whole milk. Skin prick and intradermal tests were
      negative. Patch test (48 h) was positive for whole milk and whole milk
      vehiculized in vaseline, and for alpha-lactalbumin. Total IgE was 559 kU/l; serum
      specific IgE was negative; IgG4 was positive (9.48% for alpha-lactalbumin; 7.41%
      for beta-lactoglobulin and 9.85% for casein). HRT was positive for casein (34%).
      We found precipitating antibodies to the three milk fractions in our patient and
      in the atopic control. In the challenge test, 10 h after milk intake the patient
      presented serous rhinorrea, sneezing and nasal blockade. IgG4 was involved as a
      blocking or anaphylactic antibody and as an immunological epiphenomenon
      reflecting a permanent antigenic stimulus. We find this last explanation to be
      the most coherent in this case.

PMID- 9777540
TI  - Sensitization to cockroach allergens in a sample from the urban population living
      in Naples (southern Italy).
AB  - The aim of this study was to evaluate the prevalence of allergic sensitization to
      cockroach allergens in a group of atopic patients living in the urban area of
      Naples. Four hundred and fourteen consecutive patients were submitted to the
      following diagnostic procedures: anamnestic data; clinical examination; and skin
      prick test by using a standardized pricker and allergenic extracts, one of which
      contained a mix of whole bodies of Blattella orientatis, Blattella germanica and
      Periplaneta americana. The evaluation of cockroach serum specific IgE antibodies
      was carried out in the 19 patients (4.58%) who showed a positive skin prick test
      to cockroach allergens. The majority of cockroach sensitive individuals were
      males and exhibited perennial respiratory symptoms; 17 of these patients were
      also sensitized to Dermatophagoides pteronyssinus allergens. The results of our
      study demonstrated that the prevalence of cockroach sensitization as determined
      by skin prick test in our urban area (Naples) is lower in comparison to other
      European studies. Up to now, it is not clear if the association between cockroach
      D. pteronyssinus sensitization can be determined by a cross-reactivity between
      the allergens or by their coexistence in the same indoor environments.
      Considering the absence of a visual presence of cockroaches in the indoor
      environments of our cockroach-sensitive patients we suggest the possibility of
      unrecognized exposure to cockroach materials and, moreover, the possibility of
      the carrying of such allergens from infested places on clothing, as we
      demonstrated for Fel d I.

PMID- 9777542
TI  - Fixed drug eruption induced by indapamide. Cross-reactivity with sulfonamides.
AB  - Indapamide is a nontiazidic sulfonamide diuretic which has not been previously
      reported as a cause of fixed drug eruption. We describe a patient who experienced
      several episodes of fixed drug eruption during treatment with indapamide. The
      diagnosis was confirmed by positive controlled oral challenge test. The possible
      existence of cross-reactivity with other sulfonamide derivatives was investigated
      by controlled oral challenge test with sulfamethoxazole, sulfadiazine and
      furosemide, with the tests with sulfamethoxazole and sulfadiazine resulting
      positive.

PMID- 9777543
TI  - Active lateral neck flexion range of motion measurements obtained with a modified
      goniometer: reliability and estimates of normal.
AB  - OBJECTIVE: To describe a new method for measuring lateral neck flexion range of
      motion (ROM), document the reliability of the method and present estimates of
      normal. SUBJECTS: One hundred thirty-five subjects ranging in age from 14-95 yr.
      Two physical therapists with 13 and 2 yr of experience, respectively, served as
      testers. INTERVENTION: Measurement of active lateral neck flexion ROM using a
      universal goniometer modified by the placement of a portion of a small paper clip
      through the axis. The goniometer arms were aligned with the subject's nose, and
      the free-swinging paper clip (pendulum) was used as a marker. The more
      experienced therapist measured lateral flexion of 100 subjects to establish
      intratester reliability and estimates of normal. Both therapists measured 35
      subjects to determine intertester reliability. MAIN OUTCOME MEASURE: Degrees of
      lateral neck flexion. RESULTS: Intraclass correlation coefficients for
      intratester reliability exceeded 0.90. Coefficients for intertester reliability
      were 0.86 and 0.65. ROM decreased with increasing age. CONCLUSION: The modified
      goniometer is inexpensive, easy to use and can yield high intratester reliability
      and satisfactory intertester reliability. The estimates of normal provide
      preliminary values with which a patient's lateral neck flexion ROM can be
      compared.

PMID- 9777544
TI  - An investigation of the interrelationship between manipulative therapy-induced
      hypoalgesia and sympathoexcitation.
AB  - OBJECTIVE: To investigate a proposed model in which manipulative therapy produces
      a treatment-specific initial hypoalgesic and sympathoexcitatory effect by
      activating a descending pain inhibitory system. The a priori hypothesis tested
      was that manipulative therapy produces mechanical hypoalgesia and
      sympathoexcitation beyond that produced by placebo or control. Furthermore, these
      effects would be correlated, thus supporting the proposed model. DESIGN: A
      randomized, double-blind, placebo-controlled, repeated-measures study of the
      initial effect of treatment. SETTING: Clinical neurophysiology laboratory.
      SUBJECTS: Twenty-four subjects (13 women and 11 men; mean age, 49 yr) with
      chronic lateral epicondylalgia (average duration, 6.2 months). INTERVENTION:
      Cervical spine lateral glide oscillatory manipulation, placebo and control.
      OUTCOME MEASURES: Pressure pain threshold, thermal pain threshold, pain-free grip
      strength test, upper limb tension test 2b, skin conductance, pileous and glabrous
      skin temperature and blood flux. RESULTS: Treatment produced hypoalgesic and
      sympathoexcitatory changes significantly greater than those of placebo and
      control (p < .03). Confirmatory factor-analysis modeling, which was performed on
      the pain-related measures and the indicators of sympathetic nervous system
      function, demonstrated a significant correlation (r = .82) between the latencies
      of manipulation-induced hypoalgesia and sympathoexcitation. The Lagrange
      Multiplier test and Wald test indicated that the two latent factors
      parsimoniously and appropriately represented their observed variables.
      CONCLUSION: Manual therapy produces a treatment-specific initial hypoalgesic and
      sympathoexcitatory effect beyond that of placebo or control. The strong
      correlation between hypoalgesic and sympathoexcitatory effects suggests that a
      central control mechanism might be activated by manipulative therapy.

PMID- 9777545
TI  - Random vs. systematic sampling from administrative databases involving human
      subjects.
AB  - OBJECTIVE: Two sampling techniques, simple random sampling (SRS) and systematic
      sampling (SS), were compared to determine whether they yield similar and accurate
      distributions for the following four factors: age, gender, geographic location
      and years in practice. METHOD: Any point estimate within 7 yr or 7 percentage
      points of its reference standard (SRS or the entire data set, i.e., the target
      population) was considered "acceptably similar" to the reference standard. The
      sampling frame was from the entire membership database of the Canadian
      Chiropractic Association. The two sampling methods were tested using eight
      different sample sizes of n (50, 100, 150, 200, 250, 300, 500, 800). From the
      profile/characteristics, summaries of four known factors [gender, average age,
      number (%) of chiropractors in each province and years in practice], between- and
      within-methods chi 2 tests and unpaired t tests were performed to determine
      whether any of the differences [descriptively greater than 7% or 7 yr] were also
      statistically significant. The strengths of the agreements between the provincial
      distributions were quantified by calculating the percent agreements for each
      (provincial pairwise-comparison methods). Any percent agreement less than 70% was
      judged to be unacceptable. RESULTS: Our assessments of the two sampling methods
      (SRS and SS) for the different sample sizes tested suggest that SRS and SS
      yielded acceptably similar results. Both methods started to yield "correct"
      sample profiles at approximately the same sample size (n > 200). CONCLUSION: SS
      is not only convenient, it can be recommended for sampling from large databases
      in which the data are listed without any inherent order biases other than
      alphabetical listing by surname.

PMID- 9777546
TI  - Further analysis of the reliability of the posterior tangent lateral lumbar
      radiographic mensuration procedure: concurrent validity of computer-aided X-ray
      digitization.
AB  - OBJECTIVE: To investigate the reliability of a specific method of radiographic
      analysis of the geometric configuration of the lumbopelvic spine in the sagittal
      plane, and to investigate the concurrent validity of a computer-aided
      digitization procedure designed to replace the more tedious and time-consuming
      manual measurement process. DESIGN: A blind, repeated-measures design was used.
      The results of radiographic measures derived through the traditional manual
      marking method were compared with measures derived by computer-aided digitization
      of lateral lumbopelvic radiographs. SETTING: Private chiropractic clinic. MAIN
      OUTCOME MEASURES: Pearson's product-moment correlation coefficients, paired
      sample t tests and intraclass correlation co-efficients (ICC) were used to
      examine intraexaminer reliability, and repeated measures of analysis of variance
      were used to examine interexaminer reliability for relative rotation angles for
      T12-L1, L1-L2, L2-L3, L3-L4, L4-L5, L5-S1, overall lordosis measurement [absolute
      rotation angle (ARA)] from L1-L5 and Cobb angle of overall lordosis measured from
      the inferior surface of T12 to the superior surface of S1, Ferguson's sacral base
      angle to horizontal, angle of pelvic tilt (arcuate angle) to horizontal and
      anteroposterior thoracic translation (Sz) in millimeters. RESULTS: ICC estimates
      for intraexaminer reliability were in the range of 0.96-0.98 for the L1-L5 ARA, a
      range of 0.87-0.99 for the arcuate angle measurement, 0.83-0.94 for the
      Ferguson's angle measurement, 0.88-0.95 for the Cobb angle measurement from the
      inferior surface of T12 compared with the superior surface of S1 and 0.98-1.00
      for the translation measurement of the lower thoracic spine to S1 (Sz). The
      intersegmental measurement's (T12-L1, L1-L2, L2-L3, L3-L4, L4-L5, L5-S1)
      correlations ranged from a low of 0.55 to a high of 0.97. Examination of these
      findings suggests that the reliability for the three doctors is acceptable with
      only the T12-L1 intersegmental measure falling below 0.70 for the least
      experienced examiner. Average ICC of interexaminer reliability for manual and
      computer-aided digitizing examiners were the following: 0.96 for the L1-L5 ARA;
      0.84 for the arcuate angle measurement; 0.82 for the Ferguson's angle
      measurement; 0.88 for the Cobb angle measurement; 1.00 for the Sz translation
      measurement; and values of 0.65, 0.73, 0.74, 0.75, 0.89 and 0.81 for relative
      rotation angle measurements T12-L1, L1-L2, L2-L3, L3-L4, L4-L5 and L5-S1,
      respectively. CONCLUSION: The data tend to support the reliability of this method
      of radiographic analysis of the geometric configuration of the lumbopelvic spine
      as viewed on lateral lumbopelvic radiographs. The additional data presented here
      tend to support the concurrent validity of the computer-aided digitization method
      of analysis inasmuch as the measures determined by the digitizing examiners are
      essentially identical to those determined by the manual method plus or minus the
      average standard error of measure of each value.

PMID- 9777547
TI  - Tunnel vision information: a paradox of ethics, economics, politics and science.
AB  - BACKGROUND: Improvement in vision with spinal manipulation was first observed in
      the early 1970s. Reports of the phenomenon appeared in the 1980s in the popular
      press and at scientific meetings, but it was not until the mid-1990s that general
      discussion of the potential value of this knowledge occurred. Considering the far
      reaching implications of the possible ability to improve brain function by spinal
      manipulation, the delay in consideration and implementation of this concept is a
      paradox in general terms and a total mystery in the case of the chiropractic
      profession. OBJECTIVE: To provide explanations for the delay in scientific
      assessment of the discovery that vision improves, in appropriate patients, when
      the spine is manipulated and to discuss the implications of this finding. This
      discovery is now called the "tunnel vision information." DISCUSSION: A schema of
      pathological hierarchy is depicted in which the level of intervention of spinal
      manipulation outranks other forms of treatment. The significance of this
      precedence is portrayed. Possible reasons for the failure to address this
      hierarchy in light of the tunnel vision information are discussed with reference
      to established protocols, medical politics, the presentation of the data, the
      failure of scientific editorship and the illogical aspects of the illness itself.
      CONCLUSION: In the future, the delay from the initial observation of the tunnel
      vision discovery to its free discussion in scientific literature may seem
      incongruous, particularly if the health benefits which it augurs are realized.

PMID- 9777548
TI  - Lymphedema as a cause of unilateral leg swelling: a case report with 6-yr follow
      up.
AB  - OBJECTIVE: To discuss a case of unilateral lower extremity swelling caused by an
      uncommon condition, lymphedema praecox. An emphasis is placed on diagnostic
      imaging. CLINICAL FEATURES: A 48-yr-old man suffered from low back and left leg
      pain. The left leg was swollen with evidence of cellulitis. Orthopedic evaluation
      separated the low back pain from the leg pain, and a diagnosis of sacroiliac
      syndrome concurrent with lymphedema was made. Further evaluation led to a
      diagnosis of congenital lymphedema, specifically lymphedema praecox, because of
      the age of onset. INTERVENTION AND OUTCOME: Because of active cellulitis, direct
      treatment of the lymphedema was contraindicated. The patient was advised in
      techniques to keep the leg clean and to help decrease pooling of lymph by placing
      the limb in an elevated position. The patient was also referred to a medical
      facility for antibiotics. The low back pain was addressed using chiropractic.
      CONCLUSION: Congenital lymphedema is an uncommon condition that causes unilateral
      limb swelling. The differential diagnosis includes other uncommon entities that
      should be ruled out so that proper treatment may be administered. Congenital
      lymphedema is best treated conservatively and only after any cellulitis has been
      controlled.

PMID- 9777549
TI  - Psychoneuroimmunology, the placebo effect and chiropractic.

PMID- 9777550
TI  - How real is the subluxation? A research perspective.

PMID- 9777551
TI  - Changes in brain function after manipulation of the cervical spine.

PMID- 9777552
TI  - Changes in brain function after manipulation of the cervical spine.

PMID- 9777553
TI  - Changes in brain function after manipulation of the cervical spine.

PMID- 9777554
TI  - Changes in brain function after manipulation of the cervical spine.

PMID- 9777555
TI  - Changes in brain function after manipulation of the cervical spine.

PMID- 9777556
TI  - Treatment of cervical disc protrusions via instrumental chiropractic adjustment.

PMID- 9777557
TI  - Mycotoxins and building-related illness.

PMID- 9777558
TI  - ACOEM guidelines for protecting health care workers against tuberculosis.
      American College of Occupational and Environmental Medicine.

PMID- 9777559
TI  - EPA ruling on environmental particulates and the occupational physician.

PMID- 9777560
TI  - Vibration white finger revisited.

PMID- 9777561
TI  - The NIOSH review of hand-arm vibration syndrome: vigilance is crucial. National
      Institute of Occupational Safety and Health.

PMID- 9777562
TI  - The economic costs associated with body mass index in a workplace.
AB  - This study was undertaken to determine if a progressive correlation exists
      between body mass index (BMI), health care costs, and absenteeism and to identify
      an economically optimal BMI. We studied 3,066 First Chicago NBD employees by
      using health risk appraisals and personnel data. Analysis was completed for those
      employees with and without a risk for BMI. People at risk for BMI are more likely
      to have additional health risks, short-term disability and illness absence, and
      higher health care costs than those not at risk for BMI. A "J-shaped" curve
      between health care costs and BMI exists, with the low point occurring at about
      25 to 27 kg/m2. We concluded that indirect and direct costs to an employer
      increase with increasing BMI. Employers may benefit from helping employees
      achieve a healthy weight. The initial target population should be those who are
      at highest risk of complications from obesity.

PMID- 9777563
TI  - Workplace effects of the stigmatization of depression.
AB  - Employers have previously been shown to hold negative attitudes toward mental
      illness. The purpose of this survey of human resource officers in UK companies
      was to ascertain whether these attitudes prejudice employment opportunities for
      subjects with mental illness--specifically, depression--and, if so, some of the
      beliefs upon which these attitudes are based. When employers were given vignettes
      of job applicants identical except for diagnosis, a label of depression
      significantly reduced the chances of employment, compared with one of diabetes,
      despite both being seen as equally credible illnesses. This stigmatization is
      based upon perceptions of potential poor work performance, rather than
      expectations of future absenteeism, but is not concordant with previous research.
      It is suggested that greater dissemination of information may alleviate some of
      this stigma.

PMID- 9777564
TI  - Long-term follow-up of psychological distress, social functioning, and coping
      style in treated and untreated patients with solvent-induced chronic toxic
      encephalopathy.
AB  - Patients with organic solvent-induced toxic encephalopathy (TE) (n = 13) were
      followed up seven years after the application of an intervention program. They
      were also compared with untreated TE patients diagnosed at the same time (n = 26)
      and with unexposed referents (n = 39). Psychological distress, social function,
      and coping ability and style were measured with the Symptom Checklist-90,
      Interview Schedule of Social Interaction, and Sense of Coherence and Strategies
      to Handle Stress questionnaires. Both TE groups had unchanged function in
      neuropsychological tests. Members of the treated group had improved their social
      functioning and reduced their mental stress but were not any better than the
      untreated patients. Compared with referents, the TE patients continued to live
      with increased psychological distress and used predominantly emotionally focused
      strategies to cope with their problems. This can be a cause for concern in family
      life and can also make gainful work impossible.

PMID- 9777567
TI  - Effects of the intensity and timing of asbestos exposure on lung cancer risk at
      two mining areas in Quebec.
AB  - Mortality data from 9609 workers at two asbestos mining areas in Quebec were
      analyzed to assess the effects of the intensity and timing of exposure on lung
      cancer risk. Summary exposure measures based on differing assumption were
      computed for lung cancer cases and matched controls and were fitted to the data
      using conditional logistic regression. A non-linear relationship between
      intensity and risk fit both mining areas, but risk was greater at one area than
      the other. At the mine with lower risk, exposure occurring more than 30 years
      prior to death had little effect, while at the other mine risk did not vary with
      time since exposure and men starting employment before 1924 were at elevated
      risk. The results point to differences in dust composition at the two areas and
      illustrate the difficulties in estimating risk.

PMID- 9777565
TI  - Using the National Death Index to obtain underlying cause of death codes.
AB  - This study evaluated the comparability of underlying cause of death codes
      obtained from NDI Plus, a new feature of the National Death Index (NDI), with
      codes assigned by two study nosologists or by a National Center for Health
      Statistics (NCHS) nosologist. Two study nosologists and an NCHS nosologist
      independently reviewed the death certificates of 493 decedents and assigned each
      an International Classification of Diseases code for the underlying cause of
      death. Using the NCHS codes as the reference standard, we determined discrepancy
      rates for NDI Plus codes; for each study nosologist's original codes; and for
      "final study codes," derived by comparing the two sets of study nosologists'
      codes and resolving discrepancies by using the NCHS code. For all causes of death
      combined, the discrepancy rate was 4% for NDI Plus codes, 4% for the final study
      codes and 6%-7% for the study nosologists' original codes. The discrepancy rate
      for selecting the appropriate cancer site was 1% for NDI Plus codes and 3% for
      the final study codes. For noncancer conditions, the discrepancy rate was 5% for
      NDI Plus codes and 4% for the final study codes. NDI Plus underlying cause of
      death codes are comparable to codes developed using standard but more cumbersome
      procedures. The use of NDI Plus codes may enhance the validity of comparisons of
      an occupational cohort's mortality rates with national or state rates.

PMID- 9777568
TI  - Effects of maternal work activity during pregnancy on infant malformations.
AB  - This article examines the association between two birth defects, neural tube
      defects and oral cleft defects, and maternal physical work demands during the
      periconceptional period. A case-control study was conducted by comparing exposure
      characteristics of mothers of malformed infants, as ascertained from the New York
      State Congenital Malformations Registry (n = 520), with mothers of non-malformed
      infants (n = 1154). Case groups were further subdivided on whether infants had
      additional defects. Occupational exposure information was collected from a self
      administered questionnaire, and demographic variables from vital records. The
      results showed no general differences between cases and controls in most
      variables. However, those infants with cleft defects plus additional defects
      tended to have a marginally increased risk (odds ratio = 1.76; 95% confidence
      interval, 1.02-3.21) in relation to maternal jobs requiring standing (> or = 75%
      of time). We suggest that exposure assessment be improved and defects subdivided
      for future studies.

PMID- 9777566
TI  - Respiratory findings in workers employed in the brick-manufacturing industry.
AB  - We studied 233 male workers employed in two brick-manufacturing plants and 149
      matched control workers. The mean age of the brick workers was 35 years, with a
      mean duration of employment in this industry of 16 years. The prevalence of
      chronic respiratory symptoms as well as acute symptoms during the work shift were
      recorded. Lung function was measured on Monday during the work shift by recording
      maximum expiratory flow-volume (MEFV) curves, from which the forced vital
      capacity (FVC), the one-second forced expiratory volume (FEV1) and flow rates at
      50% and the last 75% of the FVC (FEF50, FEF75) were measured. The results of
      periodic chest roentgenograms were reviewed. There was a significantly higher
      prevalence of chronic cough (31.8%), chronic phlegm (26.2%), and chest tightness
      (24.0%) in exposed workers, compared with control workers (20.1%; 18.1%; 0%) (P <
      0.05). This increased symptom frequency was also documented among nonsmokers
      studied by age and by length of employment, suggesting a work-related effect.
      Among work shift-related symptoms, high prevalences were noted for upper
      respiratory tract symptoms (e.g., dry throat, eye irritation, throat irritation).
      The measured FVC and FEV1 were significantly lower than predicted for brick
      workers and suggested a restrictive pattern. The mean FVC (as a percent of
      predicted) was 78.1% and FEV1 was 88.1%. The FEF50 and FEF25 were not
      significantly decreased. A multiple regression analysis with age, exposure, and
      smoking as predictors and lung function parameters as response variables showed a
      significant effect between exposure and FVC. Significant chest roentgenographic
      abnormalities were not documented. These findings of a restrictive lung function
      pattern in brick workers with normal chest roentgenograms may suggest early
      interstitial disease. Additionally, a bronchitic component, as suggested by the
      respiratory symptoms, may also be present.

PMID- 9777569
TI  - Leptin as a metabolic regulator during fetal and neonatal life and in childhood
      and adolescence.
AB  - Body weight is regulated by a feedback loop in which peripheral signals report
      nutritional information to an integratory center in the brain. The cloning of the
      ob gene is consistent with this concept and suggests that body fat content in
      adult rodents is regulated by a negative feedback loop centered in the
      hypothalamus/1-8/. In a recent report, two severely obese children with
      congenital leptin deficiency due to a homozygous frame-shift mutation involving
      the deletion of a single guanine nucleotide in codon 133 of the ob gene have been
      described. This discovery provides the first genetic evidence that leptin is an
      important regulator of energy balance in humans. However, it has become
      increasingly clear that apart from leptin's function in the central nervous
      system and in regulation of energy balance, leptin also acts in the periphery and
      might be important as a hormone modulating processes in regard to reproduction,
      glucose metabolism and insulin resistance, as well as growth and development of
      many tissues and organs either directly or indirectly. This report reviews some
      of the topics of leptin research that are of particular importance and relevance
      for pediatric and adolescent medicine and for pediatric endocrinology in
      particular.

PMID- 9777570
TI  - Gonadotropin independent precocious puberty.
AB  - Clinicians should now be fully aware of this intriguing condition of GIPP. The
      condition is characterized by pubertal sex steroid concentrations and
      gametogenesis in the presence of prepubertal or suppressed gonadotrophins. In
      patients with MPP especially without a family history, one should exclude the
      possibility of pseudoprecocious puberty due to premature production of sex
      steroids without pituitary gonadotrophins resulting from a primary disorder of
      the gonad or adrenal gland or to autonomous secretion of gonadotrophin by a
      tumor. Similarly in patients with recurrent ovarian cyst formation, persistence
      of the cysts especially with a significant solid component beyond three months
      should alert a clinician to the possibility of juvenile granulosa cell tumor of
      the ovary /75/. After confirmation of the diagnosis appropriate treatment should
      be instituted.

PMID- 9777571
TI  - Recognition of children with psychosocial short stature: a spectrum of
      presentation.
AB  - We describe 65 children (32F, 33M) with psychosocial short stature from 51
      families. Average age was 6.6 years (range 0.9-16.5) and all but five were
      prepubertal. 67% of the patients lived in families with three or more children,
      but in 73% of cases the patient was the first or the second born child. 45% of
      the parents were divorced and in 31% of the families the father was unemployed.
      In 56 children, the birth weight was known and in only 29% was it above 3000 g;
      21% were premature, 29% had features of low birth-weight syndrome (including four
      with Russell-Silver syndrome). Average birth weight was 2786 g (range 1650-4676).
      In all patients, the predominant reason for referral was growth failure. In 28%
      an environmental aetiology was suspected and in a further 29%, social or
      emotional problems were known to the referring physician but not suspected as the
      aetiology of the growth failure, despite social services involvement in 60% at
      the referral to our unit. At initial presentation in our clinic, we found
      additional features leading to the suspicion of psychosocial short stature; 54%
      abnormal eating pattern, 42% behaviour problems, 26% encopresis, 18% nocturnal
      enuresis and 12% inappropriate urination. During the observation period of a mean
      of 3.7 years, 27 (41%) of our patients were found to have been sexually or
      physically abused. In these 27 children hyperphagia, bizarre eating habits,
      behaviour problems, soiling and nocturnal enuresis were more common.

PMID- 9777572
TI  - True hermaphrodites in the southeastern region of Brazil: a different cytogenetic
      and gonadal profile.
AB  - Sex ambiguity may be due to several disorders of gonadal differentiation,
      including true hermaphroditism (TH), as well as male and female
      pseudohermaphroditism. Although TH is a rare cause of intersex in Europe and
      North America, in Africa it presents one of the highest frequencies. The 46,XX
      karyotype has been found in the majority of the reported patients (70.6%), and
      aberrations in the sex chromosomes have been observed in about 22% of the cases.
      The 46,XY karyotype has been described as less frequent. Herein we describe ten
      cases of TH which have been diagnosed over the last 7 years, six lateral TH, two
      unilateral TH, and two cases of ovotestes with absent contralateral gonad. From a
      total of 18 gonads analyzed, there were 8 testes, 6 ovaries and 4 ovotestes. Nine
      subjects had originally a male sex assignment, and in three cases this was
      reverted to female. Four cases had a 46,XY karyotype. Additional sex chromosome
      aberrations had been found in four different cases [two 46,XX/46,XY, one
      45,X/47,XYY, one 46,X,del(Yq)]. A 46,XX karyotype was found in only two
      individuals, and both were SRY negative. Our preliminary data, especially on the
      constitution of chromosomes and gonads, indicate marked differences from those in
      the literature.

PMID- 9777573
TI  - Pelvic ultrasound measurements in normal girls: relation to puberty and sex
      hormone concentration.
AB  - Pelvic ultrasonography was performed on 75 normal girls. Values were obtained for
      uterine length, fundal/cervical ratio (FCR), ovarian volume and sex hormones. The
      resultant data were grouped according to age and pubertal stage (Tanner). For
      uterine length, FCR and ovarian volume, the data were positively skewed, and the
      variance increased with age and pubertal stage (p < 0.001). The uterus underwent
      a regular increase in size and the corpus gradually became larger than the
      cervix. Uterine length, right ovary volume, FCR and hormones (serum estradiol,
      follicle-stimulating hormone and luteinizing hormone) showed a correlation with
      the Tanner score (p < 0.001). Although the correlations were significant, the
      best correlation was between pubertal stage and serum estradiol level.

PMID- 9777574
TI  - Hyperprolactinaemia and pituitary adenomas in adolescence.
AB  - Six adolescents, five males with prolactin-secreting pituitary macroadenomas and
      one female with idiopathic hyperprolactinaemia, are described. Their ages at
      presentation ranged from 13 years 7 months to 16 years 6 months. Presenting
      symptoms included headache, visual field defect, arrested growth and puberty.
      Only two cases had galactorrhoea. Every case had an elevated serum prolactin
      level. Three had surgery before the results of serum prolactin were to hand. Each
      patient was treated with bromocriptine. Bromocriptine suppressed serum prolactin
      level to normal in four cases, but in the girl with idiopathic
      hyperprolactinaemia, bromocriptine was not useful. In two boys, serum prolactin
      was not suppressed with bromocriptine therapy alone, and they were subsequently
      treated with cabergoline, surgery and irradiation. Nevertheless, in children and
      adolescents with prolactin-secreting pituitary adenoma, bromocriptine should be
      the first line of treatment.

PMID- 9777575
TI  - Experience with low-dose replacement therapy in the initial management of severe
      pediatric acquired primary hypothyroidism.
AB  - Rapid hormonal replacement of children with severe primary hypothyroidism
      frequently results in irritability and poor concentration. To alleviate these
      problems we have been using initial low-dose thyroxine treatment, building up to
      a final dose in an incremental manner over 4 1/2 to 6 months. Because of concern
      this regimen may compromise growth, we reviewed our experience treating 14
      children and adolescents. For the 10 patients with remaining growth potential, 5
      to 7 month growth velocity from the onset of treatment was 8.5 +/- 1.9 cm/year
      (range 5.7-10.9), and 5 to 7 month growth velocity z-score 1.5 +/- 1.7 (range 0.2
      4.9). For the entire group, the thyroxine dose required to normalize TSH was 1.6
      +/- 0.74 microgram/kg (range 0.9-3.4) or 60.7 +/- 18.9 micrograms/m2 (range 37.5
      97.7). Based on the 5 to 7 month z-score, we conclude that satisfactory growth
      can be achieved on this regimen despite biochemical hypothyroidism. Thyroxine
      doses required to induce initial euthyroidism are lower than previously proposed.

PMID- 9777576
TI  - Diurnal variation of plasma cortisol levels in infancy.
AB  - Normal children and adults show diurnal variation of plasma cortisol levels
      reaching peak values around 08.00 h and lower values around 24.00 h. Despite
      numerous studies on diurnal variation of plasma cortisol levels in children, the
      age of appearance of a circadian rhythm has not been definitely established. The
      purpose of this study was to investigate the development of cortisol circadian
      rhythm in infancy. In seventy healthy, full-term infants, less than six months
      old, plasma cortisol was measured at 10.30 h and 22.30 h. The mean +/- SEM values
      of daytime plasma cortisol at one to four weeks of life were 159 +/- 41, 116 +/-
      43, 240 +/- 54 and 456 +/- 95 nmol/l and the night-time values were 129 +/- 40,
      99 +/- 44, 131 +/- 78 and 430 +/- 105 nmol/l, respectively. No statistically
      significant differences were found between daytime and night-time cortisol values
      during the first four weeks of life. In contrast, the daytime values of plasma
      cortisol were 295 +/- 62 at the age of 2-3 months, 211 +/- 43 at 4-5 months and
      291 +/- 31 nmol/l at 6 months of life, and night-time values were 166 +/- 52, 119
      +/- 35 and 109 +/- 21 nmol/l, respectively, which were statistically significant
      (p < 0.05). These data clearly indicate that cortisol circadian rhythm starts
      between the second and third month of life.

PMID- 9777577
TI  - Incidence of insulin-dependent diabetes mellitus (0-14 years) in the Abruzzo
      Region, Italy, 1990-1995: results from a population-based register.
AB  - OBJECTIVE: To provide incidence data of insulin dependent diabetes mellitus
      (IDDM) in the Abruzzo Region, Italy in 0-14 year-old children and contribute to a
      better understanding of IDDM geographical variability throughout Italy. SUBJECTS
      AND METHODS: All incident cases younger than 15 years first diagnosed with IDDM
      according to the WHO criteria between 1 January 1990 and 31 December 1995 and
      resident in the Abruzzo Region were recorded. The primary sources were divisions
      of pediatrics, endocrinology or medicine, diabetic centers for adult patients and
      the Regional Pediatric Diabetology Centre. Secondary independent sources included
      registered prescriptions for insulin in local district units of the National
      Health System and the regional IDDM association for children. RESULTS: During the
      six years, 117 new cases of IDDM in the age-group 0-14 were identified, with an
      overall standardized incidence rate of 9.34/100,000/year (95% C.I. 7.76-10.95).
      The crude incidence rate was highest in the 10-14 year age-group (10.64, 95% C.I.
      7.66-13.62). Teramo province showed the highest standardized incidence rate,
      10.30/100,000/year (95% C.I. 6.58-14.02); it is noteworthy that the IDDM rate in
      Teramo (15.40/100,000/year) was the highest in peninsular Italy in 1994. Abruzzo
      Region shows significantly higher rates than other central Italian regions. No
      significant difference in rates between males and females was observed.
      Seasonality was not observed from incidence data. CONCLUSIONS: We report the
      highest incidence rate for IDDM in children in the Italian mainland in the years
      1990-95. Our findings confirm the need for epidemiological research to provide
      more information about the distribution of genetic markers and the etiologic role
      of environmental factors in Italian regions.

PMID- 9777578
TI  - An improved polymerase chain reaction (PCR) protocol for unambigous detection of
      growth hormone gene deletions.
AB  - hGH-1 gene deletions are detected by simultaneous PCR amplification along the two
      homologous DNA sequences flanking the hGH-1 gene on both sides and are
      differentiated by SmaI restriction enzyme digestion. We have observed that among
      the SmaI digested PCR products from normal homozygous subjects, from those
      heterozygous for the 7.6 kb deletion and from those heterozygous for a 6.7 kb
      deletion, along with the expected fragments there is an unexpected 1470 bp
      fragment. This fragment arises from the co-amplification of a third homologous
      sequence located downstream from the hGH-1 gene and it confuses differentiation
      between normal homozygous and heterozygous for 7.6 kb subjects from the 6.7 kb
      heterozygous subjects. To overcome this problem we have improved PCR conditions
      using a different reverse primer. These changes avoid the interaction of the
      primers with the third homologous sequence located downstream from the hGH-1 gene
      and prevent the appearance of this additional band that complicates the
      interpretation of the results. We conclude that the new reverse primer sequence
      avoids the amplification of the downstream hGH-1 gene sequence and the production
      of the 1474 bp band after SmaI endonuclease enzyme digestion and makes it
      possible to differentiate homozygous normal subjects and those who are
      heterozygous for a 7.6 kb deletion from those who are heterozygous for a 6.7 kb
      deletion.

PMID- 9777579
TI  - Collodion baby concomitant with congenital hypothyroidism: a patient report and
      review of the literature.
AB  - Collodion baby is a rare congenital disorder resembling harlequin fetus but is
      milder in degree. Although it has been reported that harlequin fetus is
      associated with kidney abnormalities, malignant keratoma, micromelia,
      polydactyly, thymic atrophy and thyroid aplasia, there are few reports of
      collodion baby associated with congenital abnormality and/or disease in the
      literature. A newborn infant admitted with shedding of the skin and diagnosed as
      collodion baby concomitant with congenital hypothyroidism is presented here. This
      is the first case of collodion baby associated with congenital hypothyroidism in
      the literature to our knowledge.

PMID- 9777580
TI  - Congenital diabetes in an infant with trisomy 21.
AB  - A newborn infant with trisomy 21 was found to have congenital diabetes which
      appears to be permanent. Congenital diabetes is extremely rare and differs from
      type I or type II diabetes. It has never been reported previously in Down's
      syndrome and it seems to be due to a selective beta cell defect with undetectable
      C-peptide but normal alpha-cell function.

PMID- 9777581
TI  - Expression of receptors for basic fibroblast growth factor on human periodontal
      ligament cells.
AB  - Basic fibroblast growth factor (FGF-2; bFGF) is a major mitogen for connective
      tissue cells, and participates in the healing process. It has already been
      reported that FGF-2 could be applicable to enhance periodontal regeneration. In
      the present study, we examined FGF receptor (FGFR) expression on human
      periodontal ligament (PDL) cells. The binding of [125I]-labeled FGF-2 to human
      PDL cells was studied by radioreceptor assay. The binding of [125I]-FGF-2 to PDL
      cells reached a plateau after 2.5 h incubation at 4 degrees C and was inhibited
      by the addition of unlabeled FGF-2 and acidic FGF (FGF-1; aFGF), but not insulin
      like growth factor-I, platelet-derived growth factor and transforming growth
      factor-beta 1. Scatchard analysis revealed the presence of approximately 1.0 x
      10(5) FGF-2 binding sites per cell with an apparent Kd of 1.2 x 10(-10) M.
      Interestingly, the binding of [125I]-FGF-2 on PDL cells reached its maximum at d
      6 of the culture and then gradually decreased. Scatchard analysis also
      demonstrated that the number of FGFRs on a PDL cell was altered during the course
      of the culture, while the affinity between FGF-2 and its receptor was not. The
      responsiveness of PDL cells to FGF-2, which was monitored by the inhibitory
      effect on alkaline phosphatase activity, was reduced in proportion to the
      decrease in the number of FGFRs on the PDL cells. The present study suggests that
      PDL cells alter the responsiveness to FGF-2 during the course of the culture by
      changing the density of its receptor, and that the density of FGFR expression
      might be a marker of the cytodifferentiation of PDL cells into mineralized tissue
      forming cells.

PMID- 9777582
TI  - Biofilm formation by Porphyromonas gingivalis and Streptococcus gordonii.
AB  - Confocal scanning laser microscopy (CSLM) was used to visualize and quantify
      biofilm formation by the oral bacteria Streptococcus gordonii and Porphyromonas
      gingivalis. A saliva-coated glass coverslip under continuous bacterial challenge
      and conditions of low shear force was used to investigate attachment to the
      salivary pellicle and also the effect of cell-cell interactions on the extent of
      colonization and biofilm development. S. gordonii bound to the salivary pellicle
      and outcompeted P. gingivalis for attachment sites. Both P. gingivalis and S.
      gordonii failed to establish substantial biofilm formation independently.
      However, biofilm formation did occur subsequent to initial adherence of P.
      gingivalis to S. gordonii cells deposited on the salivary pellicle. The commensal
      species S. gordonii may, therefore, provide an attachment substrate for
      colonization and biofilm accretion by the potential pathogen, P. gingivalis.

PMID- 9777583
TI  - Fluid dynamics of gingival tissues.
AB  - Gingival hydraulic interstitial pressure was measured with glass micropipettes in
      18 anesthetized rabbits at the level of the free gingiva, attached gingiva and
      oral mucosa facing the incisors and molar teeth. Samples of gingival interstitial
      tissue fluid were also collected by inserting nylon wicks in the subepithelial
      layer of the oral mucosa. Colloid osmotic pressure of interstitial fluid samples
      was measured with an osmometer whose membrane had a molecular cutoff of 30 kD.
      Hydraulic interstitial pressure from the free gingiva, at an average distance of
      300 microns from sulcular space, was -1.3 +/- 0.9 (SD) cmH2O. Mean colloid
      osmotic pressure of gingival tissues interstitial fluid was 13.1 cmH2O,
      corresponding to a protein concentration of 2.8 g/dl. The thickness of the
      sulcular epithelium and of the oral gingival epithelium (data from 2 rabbits)
      were approximately 100 microns; the minimal distance of microvessels from the
      surface of the sulcular epithelium was approximately 150 microns. Based on
      hydraulic and colloid osmotic data, the Starling balance of pressures causes
      fluid filtration from gingival capillaries to gingival interstitium; however,
      across the sulcular epithelium, the pressure gradient sustains fluid absorption
      from the sulcus into the gingival interstitium. Plasma proteins may leak from
      microvessels into gingival interstitium, down convective bulk flow and via a
      concentration dependent diffusive component. At sulcular level, proteins may leak
      into the sulcus down a concentration gradient. Thus, at sulcular level a peculiar
      condition occurs in that there is an absorption gradient for water but a
      filtration gradient for plasma proteins.

PMID- 9777584
TI  - The effect of transforming growth factor beta one (TGF-beta 1) on wound healing,
      with or without barrier membranes, in a Class II furcation defect in sheep.
AB  - The purpose of this study was to analyse the effect of TFG-beta 1 on wound
      healing in standardized Class II furcation defects of 48 mandibular second
      premolar teeth in 24 sheep. The experimental design included a control group
      (carrier only, 25% pluronic F-127), and 2 experimental groups: group A (80
      micrograms/ml TGF-beta 1 + carrier) and group B (80 micrograms/ml TGF-beta 1 +
      carrier covered with a barrier membrane). Sheep were killed either 2 wk or 6 wk
      after surgery. Mesiodistal sections of the decalcified specimens were quantified
      histologically using stereology. Percentage volumes of regenerated bone, fibrous
      connective tissue and cementum were calculated for each furcation defect. Mean
      values were analysed using multiple ANOVA; p values were calculated using paired
      and unpaired Student's t-tests. After 2 wk there was more bone in group B than
      either of the other 2 groups, but this was not statistically significant. By 6 wk
      more bone was present in group A than in the control group (p < 0.02) and also in
      group B when compared with both group A and the control group (p < 0.02 and p <
      0.44), respectively. In the 4 wk between sampling significantly more bone had
      formed (group A < 0.05 and group B p < 0.003, respectively). A negative
      correlation existed between volumes of bone and fibrous connective tissue and no
      significant differences between the volumes of cementum were evident between any
      of the groups. This study demonstrated that TGF-beta 1 encouraged bone
      regeneration in Class II furcation defects in sheep, an effect enhanced by the
      presence of a barrier membrane. This is the first report on the use of TGF-beta 1
      in conjunction with GTR in periodontal defects.

PMID- 9777585
TI  - Distribution of macrophage lineage cells in rat gingival tissue after topical
      application of lipopolysaccharide: an immunohistochemical study using monoclonal
      antibodies: OX6, ED1 and ED2.
AB  - To discuss the role of macrophage lineage cells on the periodontal tissue
      destruction, we immunohistochemically examined the phenotype and the dynamics of
      macrophage lineage cells 1 or 3 h or 1, 2, 3 or 7 d after topical application of
      LPS (5 mg/ml in physiological saline) from the rat gingival sulcus using 3
      monoclonal antibodies: OX6 (antigen-presenting cells), ED1 (monocytes,
      macrophages and dendritic cells) and ED2 (resident macrophages). We could detect
      at least 3 different types of macrophage lineage cells, namely OX6+/ED1+/ED2-
      dendritic cells and exudate macrophages and ED2+ resident macrophages. After LPS
      application the majority of macrophage lineage cells accumulated in the
      subjunctional epithelial area were newly extravasated OX6+/ED1+/ED2- dendritic
      cells or macrophages. The number of these cells increased progressively with time
      and reached a maximum level at d 2. On the other hand, number and tissue
      distribution of ED2+ resident macrophages did not change. These results indicate
      that several types of macrophage lineage cells exist in rat gingival tissue and
      suggest that dendritic cells and exudate macrophages transiently accumulated
      after LPS application are responsible for various host immune response and tissue
      destruction caused by LPS.

PMID- 9777586
TI  - Effect of projective aspects variations on estimates of changes in bone mass
      using digital subtraction radiography.
AB  - This study tests the hypothesis that estimates of changes in bone mass derived
      from subtraction data obtained in accord with published methods are independent
      of the spatial aspect of the lesion being evaluated when calibrations are
      performed independently. Nineteen sliver-shaped bone chips ranging in mass from
      approximately 1 to 35 mg were orientated with broad side parallel to the facial
      surface of a hemisectioned dry human mandible and radiographed using conventional
      exposure parameters on conventional E-speed dental X-ray film. Also attached to
      the film was a standardized aluminium calibration wedge that facilitated
      quantitative analysis of resulting subtraction data using established
      methodology. The effects of scatter were simulated by the addition of a 1-cm
      thick slab of tissue-equivalent plastic. A second series of exposures then was
      produced using the same respective spatial chip locations and projection
      geometries but each chip was reorientated such that its broad side was now
      positioned perpendicular to the mandibular facial surface. Finally, a comparable
      series of control exposures was produced without any chips or calibration wedge
      to facilitate subtraction. When paired bone estimates derived from the two chip
      orientations were compared (paired comparisons) using Student's t-test, a
      statistically significant difference (p < 0.05) was observed. These results also
      were tested for statistical significance using the non-parametric Wilcoxon test.
      As with the parametric analysis, the discrepancy between the parallel and
      perpendicular mass estimates was found to statistically significant (p < 0.05).
      The methods employed in this investigation thus resulted in bone mass estimates
      that varied significantly depending upon lesion orientation.

PMID- 9777587
TI  - Alterations of neutrophil L-selectin and CD18 expression by tobacco smoke:
      implications for periodontal diseases.
AB  - Alterations in neutrophil functions by both chronic low levels of tobacco and by
      acute short-term higher levels of tobacco smoke, as encountered during the act of
      smoking, may play a role in the pathogenesis of periodontal diseases in smokers.
      Among the early migration events of neutrophil function is the alteration in
      surface expression of L-selectin and the CD11/18 integrins. In the present study
      we examined the effect of in vitro smoke exposure and nicotine alone on the
      expression of these 2 adhesion molecules in neutrophils from smokers and non
      smokers. We also determined the physiological relevance of this in vitro system
      by assessing the levels of nicotine exposure in this in vitro system and
      comparing these levels to acute and chronic levels of nicotine in saliva and
      gingival crevicular fluid. Peripheral neutrophils were isolated from the blood of
      smokers (> 1 pack/d) and non-smokers and incubated in vitro with either cigarette
      smoke (0-5 min), 10(-7) M F-met-leu-phe, or nicotine alone at 1.62 mg/ml to 162
      ng/ml (10(-2) M-10(-6) M). The neutrophils were then incubated with fluoresceine
      conjugated anti-Leu8 (L-selectin), anti-CD18 (CD18 integrin), or gamma-4 (non
      specific control), fixed and analyzed by flow cytometry. With cigarette smoke
      exposure, there was an approximate 75% shedding of L-selectin in both smokers and
      non-smokers with no marked difference between groups at 1-5 min of smoke
      exposure. Cigarette smoke exposure resulted in a 15-20% increase in CD18
      expression in both smokers and non-smokers. At all time points, there was
      slightly greater but statistically insignificant expression of CD18 integrin in
      non-smokers when compared to smokers. These patterns of CD18 increases and L
      selectin shedding were similar in magnitude to incubations with 10(-7) M F-met
      leu-phe. Acute smoke exposure resulted in elevation of nicotine in the smoke box
      to 529 ng/ml at 5 min, in saliva from 109.2 ng/ml before smoking to 1821.4 ng/ml
      after smoking, and in gingival crevicular fluid to 5961 ng/ml after smoking. No
      significant alterations in L-selectin or CD18 expression were noted with in vitro
      nicotine from 1.62 mg/ml to 162 ng/ml.

PMID- 9777588
TI  - Detection of Prevotella intermedia in subgingival plaque of adult periodontitis
      patients by polymerase chain reaction.
AB  - A PCR assay was developed that could specifically amplify DNA from the
      periodontal pathogen Prevotella intermedia. A pair of primers was selected from
      regions of the 16S rRNA gene of P. intermedia that were both divergent in
      sequence at their 3' ends with respect to the corresponding regions of the 16S
      rRNA gene of P. nigrescens, its most closely related species, and used in the PCR
      assay. Positivity was indicated by amplification of an 855 bp product. Using
      purified genomic DNA from these 2 species, assay conditions were determined under
      which only P. intermedia DNA and not P. nigrescens DNA was amplifiable. Absolute
      specificity of the assay was confirmed by the fact that no amplification products
      were obtained when using DNA from several other important periodontal organisms.
      The optimized PCR assay was used to identify P. intermedia in subgingival plaque
      samples of patients with adult periodontitis. Confirmation of amplification of P.
      intermedia DNA was achieved by digestion of PCR products with the restriction
      endonuclease RsaI, which gives different restriction patterns for P. intermedia
      and P. nigrescens. Of the 97 samples analysed, 38 (39%) were positive for P.
      intermedia. The results obtained confirm P. intermedia as a possible aetiological
      agent of adult periodontitis. Additionally, PCR primers targeting the
      corresponding region of the 16S rRNA gene of P. nigrescens were shown to be
      specific for the organism when used in a PCR assay, although P. nigrescens was
      not detectable in any of the subgingival plaques analysed.

PMID- 9777589
TI  - In vitro modulation of human gingival epithelial cell attachment and migration by
      minocycline-HCL.
AB  - Although the influence of tetracyclines on periodontal connective tissue cells
      has been the topic of many in vitro and in vivo studies, data regarding their
      effects on gingival epithelial cells are scarce. The present in vitro study was
      designed to examine the influence of minocycline, a semi-synthetic analog of
      tetracycline, on human gingival keratinocyte (HGK) attachment and migration.
      Attachment tests were performed with HGK prelabeled by tritiated amino-acids.
      Increasing concentrations of minocycline (10, 50, 100 micrograms/ml) in the
      medium produced no significant modification of cell adhesion kinetics compared to
      control conditions, except for 100 micrograms/ml which statistically
      significantly (p < 0.05) reduced the number of attached cells beyond 6 h. A 24-h
      cell preincubation in 10 micrograms/ml of minocycline did not alter the kinetics
      of HGK attachment. Scanning electron microscopic observations of attached HGK
      showed that the presence of 10 micrograms/ml of minocycline in the "attachment
      medium" induced the production of multiple filopodial extensions. Migration tests
      in Boyden chambers for 40 h demonstrated that HGK preincubation for 24 h in a 10
      micrograms/ml minocycline-HCl solution increased significantly (p < 0.005) cell
      migration towards a gradient of fetal calf serum. The presence of 10
      micrograms/ml of minocycline in contact with the keratinocytes in the upper
      compartment of the migration chambers also produced a significant (p < 0.005)
      result. In contrast, the presence of minocycline in the lower compartments did
      not produce any chemoattractive effect. Within the limits of their significance,
      these results suggest that, at concentrations not beyond 50 micrograms/ml,
      minocycline could fasten the periodontal wound coverage by epithelial cells and
      allow the normal reformation of a junctional epithelium.

PMID- 9777590
TI  - Elastic modulus, permeation time and swelling ratio of a new porcine dermal
      collagen membrane.
AB  - The goal of a single step therapy has been an important consideration in the
      development of guided tissue regeneration devices. It would spare the patient
      from the need for repeated surgery and eliminate many problems associated with a
      non-resorbable barrier. Animal studies of a collagen membrane extracted from
      porcine dermis (PDCM), as conditioned by different concentrations of
      glutaraldehyde (GA), have shown it to be biocompatible and biodegradable (up to 9
      wk). This in vitro study further investigated the physical properties of this
      membrane. A PDCM modified and cross-linked with various concentrations (0.01%,
      0.05% and 3.00%) of GA was used. A similar control series was not conditioned. At
      least 4 specimens for each experimental condition were prepared. The elastic
      modulus (EM) was measured by a universal testing machine. In the permeability
      test, Al2O3 particles of different sizes (5-23 microns) were mixed with normal
      saline to make 5 v/v% suspension and the time needed for collecting 7.5 ml of the
      filtered suspension from 10 ml suspension was recorded. Swelling ratio (gamma)
      was also measured according to gamma = 1/Vf (volume fraction). Data were analysed
      using ANOVA and Tukey's LSD test. The EM (40.8 +/- 3.8 gf/mm2) for the GA
      conditioned membranes showed no significant difference but was greater (p < 0.05)
      than that of the control. There was a significant increase (100-300%) in the
      permeation time with GA concentration (control 0.168 vs. 3% GA 0.100). The
      results suggest that the physical properties of the GA conditioned PDCM
      (especially in 3%) may fit the clinical requirements of membrane materials used
      in guided tissue regeneration techniques.

PMID- 9777591
TI  - Human cementum tumor cells have different features from human osteoblastic cells
      in vitro.
AB  - Cells obtained from human cementoblastoma and alveolar bone were isolated and
      cultured. Initial and late stages of mineralization were assessed by using atomic
      force microscopy, scanning electron microscopy and X-ray microanalysis. In
      cultures of cementoblastoma-derived cells the initial stages of mineralization
      showed well-defined spherical-shaped structures, while the osteoblastic cells
      showed plaque-like deposits. These morphological patterns of mineral deposition
      could serve as nucleation centers for hydroxyapatite crystals. Late stages of
      mineralization at 28 and 35 d maintained those morphological differences
      established in initial cultures. The material deposited by cementoblastoma and
      osteoblastic cells, analyzed by EDX spectra, revealed similar Ca/P ratios for
      both cell types. These values were similar to those reported for hydroxyapatite
      in enamel and bone. Alkaline phosphatase specific activity (AlP), of osteoblastic
      cells at 3, 7 and 11 d, showed an increase of 27.9, 50.9 and 37.0% (p < 0.001),
      respectively. However, at 15 and 19 d there was an increase of AlP activity of
      cementoblastoma cells by 39.4 and 34.5% over osteoblastic cells (p < 0.001).
      Immunostaining of cementoblastoma and osteoblastic cells using a specific mAb
      against a cementum-derived attachment protein revealed strong immunostaining of
      cementoblastoma cells which was localized to the cell membrane and fibril-like
      structures (96.2 +/- 1.3). A few osteoblastic cells also stained weakly with the
      anti-CAP mAb (6.4 +/- 0.6). Sections of decalcified paraffin embedded
      cementoblastoma specimens, when immunostained with anti-CAP mAb, showed strong
      immunostaining of the cells surrounding the regular and irregularly-shaped
      calcified masses of the tumor. Putative cementocytes also stained positively.
      Immunostaining with a polyclonal antibody against osteopontin strongly stained
      the osteoblastic cells (89.0 +/- 3.6). Cementoblastoma cells showed weaker
      staining (54.2 +/- 2.4). The results suggest that cementoblastoma cells could be
      a major source of specific cementum proteins. These cells could provide the
      opportunity to elucidate the regulation of the cementogenesis process.

PMID- 9777592
TI  - Periotron 8000: calibration characteristics and reliability.
AB  - The Periotron is an instrument designed to quantify submicrolitre volumes of
      fluid sampled on a filter paper strip. To date 3 models have been manufactured:
      the Periotron 600 (1976), the Periotron 6000 (1983) and more recently the
      Periotron 8000 (1995). This paper investigated for the first time the calibration
      characteristics and reliability of the Periotron 8000. The fluids under
      investigation were: de-ionised water, human serum, fetal bovine serum and an
      ultrafiltrate of fetal bovine serum. Quantitative analysis was studied by
      recording a series of Periotron readings over a volume range of 0-1.0 microliters
      for each fluid. The average of 5 Periotron values for each particular fluid was
      then plotted versus the respective fluid volume. Qualitative changes in fluid
      composition versus Periotron Scores were also analysed. Volume conversion for
      Periotron scores using both Periotron MLCONVRT software and a best fit equation
      selected from TableCurve 2D software compared well. The results of this study
      revealed that: 1) differences in calibration fluid composition (e.g. protein
      content) are reflected in the Periotron scores; 2) positioning of filter paper
      strip between the jaws of the Periotron should be standardised, 3) calibration of
      the Periotron 8000 seems to be consistent over a 1-wk interval.

PMID- 9777593
TI  - Use of hyaluronic acid binding protein for detection of hyaluronan in ligature
      induced periodontitis tissue.
AB  - This study was designed to demonstrate, by use of biotin-labeled hyaluronic acid
      binding protein (HABP) and an avidin-enzyme system, the localization of
      hyaluronan (HA) in periodontal tissue of beagle dogs during experimentally
      induced periodontitis. Experimental periodontitis was induced in the dogs by
      ligation of the gingival sulcus. Experimental tissue was collected at 0, 3, 7 and
      21 days after ligation. HA was revealed by strong staining in the intercellular
      space around epithelial cells and periodontal ligament, and by light staining in
      the gingival connective tissue. According to the progression of periodontal
      tissue breakdown, HA was detected in a small number of leukocytes and monocytes,
      on the surface of osteoclasts, the surface of alveolar bone, thickened
      endothelium and in epithelial cells related to rete peg formation. Streptomyces
      hyaluronidase-treated specimens gave negative staining. This study suggests that
      HA may be associated with the inflammatory reaction in experimental periodontitis
      tissue.

PMID- 9777594
TI  - Histological alterations following short-term smokeless tobacco exposure in
      humans.
AB  - The purpose of this study was to investigate the histological changes following
      short-term smokeless tobacco application in humans. Sixteen smokeless tobacco
      using subjects participated in this trial. Each subject had used at least 3 cans
      of snuff per week for the previous 2 yr and had an existing lesion at the site of
      habitual snuff placement. The experimental design included subject placement of
      moist snuff (University of Kentucky reference tobacco brand 1S3) at a new site in
      the mandibular arch. At either 2 or 7 d, biopsies were taken from the new lesions
      and from a non-placement site in the opposing arch. The volume density of
      inflammatory cells was determined by point counting. Keratin and epithelial
      thickness were evaluated by digitizing morphometry. Data were analyzed by
      repeated measures analysis of variance. In 7-d lesions, increased keratin
      thickness was observed at the new sites compared to the non-placement sites (p =
      0.05). Increased volume density of fibroblasts (p = 0.027) and decreased volume
      densities of macrophages (p = 0.0083) and mast cells (p = 0.05) were observed at
      2 d in new versus non-placement sites. Clinically, the new sites showed erythema,
      erythema plus ulceration, or white striations. This study demonstrated
      histological and clinical changes at new snuff placement sites in as few as 2-7
      d, underscoring the rapidity of tissue alterations following snuff use.

PMID- 9777595
TI  - Dissolution of type I collagen fibrils by gingival fibroblasts isolated from
      patients of various periodontitis categories.
AB  - The classification of periodontitis in various disease categories, including
      juvenile periodontitis, rapidly progressive adult periodontitis and slowly
      progressive adult periodontitis is based mainly on differences in disease
      progression and age group susceptibility. Because dissolution of collagen fibers
      is an integral part of periodontal attachment loss, we investigated whether the
      clinical differences among these periodontitis/control groups are reflected in
      the collagen-degrading activity of gingival fibroblasts isolated from affected
      tissues. All fibroblast strains isolated from the 4 groups (n = 48) displayed
      cell-associated collagenolytic activity when seeded in contact with a
      reconstituted film of type I collagen fibrils. Cells from the control group (n =
      14) dissolved the collagen fibril film twice as fast as those from each of the 3
      disease groups (juvenile periodontitis (n = 13), rapidly progressive adult
      periodontitis (n = 7), and slowly progressive adult periodontitis (n = 14)). Both
      interleukin-1 beta and phorbolester accelerated the rate of dissolution 2-4-fold,
      but even after cytokine or phorbolester stimulation control cells were still
      considerably more effective in dissolving the collagen fibrils than cells from
      the disease groups. The observation made in this study, that dissolution of
      collagen fibrils by gingival fibroblasts from periodontally diseased individuals
      is significantly slower than by cells from healthy control subjects, challenges
      disease paradigms based on a direct relationship between collagenolytic potential
      and disease activity.

PMID- 9777596
TI  - Increased adhesion of peripheral blood neutrophils from patients with localized
      juvenile periodontitis.
AB  - Adhesion of peripheral blood neutrophils from 5 patients with localized juvenile
      periodontitis (LJP) and age- and gender-matched healthy controls was measured
      using a semi-automated 96-well microtiter plate assay method. Both unstimulated
      and formyl-methionyl-leucyl-phenylalanine (FMLP, 10-1000 nM)-stimulated
      neutrophils from LJP patients showed in general higher adhesion than did their
      controls. After 15-60 min incubation with 100 and 1000 nM FMLP the numbers of
      adherent cells were significantly (p < 0.05), 2.1-2.6-fold higher in LJP patients
      than in controls. Neutrophils from these LJP patients showed also enhanced
      respiratory burst activity in response to unopsonized zymosan stimulation. To
      test whether a decrease in intracellular diacylglycerol (DAG) kinase activity
      could account for the increased neutrophil adhesion of LJP patients normal
      neutrophils were treated with R59949 (10 microM), a DAG-kinase inhibitor. Both
      unstimulated and FMLP-stimulated normal neutrophils showed significantly (p <
      0.05) enhanced adhesion after R59949-treatment. Taken together, our data indicate
      that neutrophils from the 5 LJP patients investigated here exhibit 2 parallel
      hyperactivities, namely increased adhesion and enhanced production of reactive
      oxygen species. Furthermore, our present and previous (Hurttia et al., J
      Periodont Res 1997; 32: 401-407) results suggest that the observed neutrophil
      functional abnormalities in some LJP patients may be associated with decreased
      cellular DAG-kinase activity. It is proposed that the hyperadherent and -active
      neutrophils may promote the development of LJP by causing tissue damage in the
      periodontium.

PMID- 9777597
TI  - A study of the proliferative activity of the long junctional epithelium using
      argyrophilic nucleolar organizer region (AgNORs) staining.
AB  - The proliferative activity of the long junctional epithelium (LJE) in rats was
      examined using stains for argyrophilic proteins of the nucleolar organizer region
      (AgNORs protein). The LJE was experimentally produced by insertion of a rubber
      piece between maxillary molars for 1 wk. After removal of the rubber, the length
      and AgNORs parameters of the LJE were measured and analyzed statistically. The
      LJE widely covered the apical side of the exposed root surface 4 wk after the
      removal. Its length was longest after 4 and 8 wk; it became shorter subsequently.
      The AgNORs were visible as black dots of various sizes and numbers on the
      sections. A high potential for proliferation was obvious in the LJE after 4 wk
      and was maintained until 12 wk after the removal. The AgNORs ratio on the
      connective tissue interface of the LJE was about twice of that of normal
      junctional epithelium after 4-12 wk. The proliferative activity on the root
      surface side was slightly increased after 4 wk. There was no significant
      difference in proliferative activity between the coronal and apical sides. These
      results suggest that the proliferative activity of the LJE is maintained
      continuously at a high level on the connective tissue interface supplying the
      epithelial cells. Basal cells proliferate at the connective tissue interface of
      the LJE, migrate directly to the root surface or via the apical portion and
      finally desquamate from the surface of the epithelium.

PMID- 9777598
TI  - Absence of Malassez epithelial rests in the regenerated periodontal ligament. A
      pilot study in the monkey.

PMID- 9777599
TI  - Radioimmunoassay for TA-0910, a new stable thyrotropin releasing hormone analogue
      and its metabolite, TA-0910 acid-type, in human plasma and urine.
AB  - Radioimmunoassay (RIA) was investigated for the determination of TA-0910 and its
      main metabolite, TA-0910 acid-type, in human plasma and urine. TA-0910 is a new
      metabolically stable analogue of thyrotropin releasing hormone (TRH). Antiserum
      was raised in the rabbit against the 1-fluoro-2,4-dinitrophenyl derivative of TA
      0910 or TA-0910 acid-type conjugated to keyhole limpet hemocyanin (KLH). The
      radioligand was prepared by iodination with 125I of the histidine imidazole ring
      of TA-0910 or TA-0910 acid-type. Cross-reactivities of anti-TA-0910 or TA-0910
      acid-type antiserum for TA-0910, its metabolite and related compounds were low.
      The calibration range was 0.02-5 ng ml-1 using 100 microliters human plasma or
      urine. Inter-day variations of TA-0910 and TA-0910 acid-type assay in plasma were
      3.5-15.5 and 1.8-9.4%, respectively. The variations of the assay in urine were
      the same as those in plasma. The recovery of TA-0910 and TA-0910 acid-type spiked
      in plasma or urine samples was approximately 100%. Furthermore, this method was
      applied to the determination of TA-0910 and TA-0910 acid-type in human plasma and
      urine samples, for the evaluation of the pharmacokinetics of TA-0910 in humans.
      From the results it was demonstrated that he developed RIA was useful for the
      determination of TA-0910 and TA-0910 acid-type in human plasma and urine, and was
      applicable to pharmacokinetic studies in humans.

PMID- 9777600
TI  - Determination of l-menthol in pharmaceutical products by high performance liquid
      chromatography with polarized photometric detection.
AB  - A simple analytical method for l-menthol by high-performance liquid
      chromatography with a polarized photometric detector was established. The
      polarized photometric detector was constructed with two polarizers mounted on
      both sides of the flow cell in a conventional photometric detector and can be
      easily used for the detection of optically active compound, such as l-menthol.
      This study was conducted with a newly developed split-cell assembly in order to
      increase the sensitivity. The characteristic of this method is the ability to
      determine optically active compounds selectively among the other coexisting
      materials and the pretreatment of the sample can be very simple or not required
      at all. The detection of l-menthol by this method is 0.5 microgram. A good
      agreement was shown between another commonly used GC method and the method
      described in this paper.

PMID- 9777601
TI  - Quantitation of vancomycin and its crystalline degradation product (CDP-1) in
      human serum by high performance liquid chromatography.
AB  - The delayed clearance of vancomycin results in accumulation of vancomycin
      crystalline degradation product, CDP-1, in the bodies of renally impaired
      patients. The 2 isomers, CDP-1-M (major) and CDP-1-m (minor), of CDP-1 are
      antibiotically inactive but cross-react with some immunoassays that use
      polyclonal antibodies resulting in falsely elevated results. A high performance
      liquid chromatographic (HPLC) method was developed to quantitate vancomycin and
      CDP-1 in the serum of renal patients. After solid phase extraction of 200
      microliters serum, the separation of vancomycin, the 2 isomers of CDP-1 and the
      internal standard (cefazolin) was accomplished by gradient HPLC on a reversed
      phase C18 column with detection at 210 nm. Linearity was established from 1 to 25
      and 25 to 100 micrograms ml-1 vancomycin and 1 to 25 micrograms ml-1 CDP-1.
      Coefficients of variation for vancomycin and CDP-1 were 3.3-8.6% (n = 10) and 2.8
      5.2% (n = 8).

PMID- 9777602
TI  - High performance thin-layer chromatographic method for the determination of
      sparfloxacin in human plasma and its use in pharmacokinetic studies.
AB  - A rapid and sensitive high-performance thin-layer chromatographic (HPTLC) method
      has been developed for the measurement of sparfloxacin in human plasma and its
      use for pharmacokinetic study has been evaluated. Detection and quantitation were
      performed without using an internal standard. A single stage extraction procedure
      was followed for extracting sparfloxacin from plasma and a known amount of the
      extract was spotted on precoated silica gel 60 F254 plates using a Camag Linomat
      IV autosampler. Sparfloxacin was quantified using a Camag TLC Scanner 3. The
      recovery study of authentic analytes added to plasma at 0.1 to 0.8 microgram ml-1
      was 94.9 +/- 0.98% and the lowest amount of sparfloxacin that could be detected
      was 50 ng ml-1 plasma. The method provides a direct estimate of the amount of
      sparfloxacin present in plasma. The method was used for the determination of
      plasma levels as well as pharmacokinetic parameters of sparfloxacin after oral
      administration of two marketed preparations to healthy volunteers.

PMID- 9777603
TI  - Determination of buprenorphine in plasma by liquid chromatography: application to
      heroin-dependent subjects.
AB  - A rapid, sensitive, precise and accurate HPLC assay with UV detection was
      developed for the determination of buprenorphine (BN) in human plasma. This
      method involved a two-step extraction in the presence of clothiapine as internal
      standard. The compounds were chromatographied on a reversed-phase Spherisorb C8
      column with a mobile phase consisting of 0.06 M KH2PO4/Na2HPO4 pH 6.4
      acetonitrile-triethylamine-Pic B5 (520:480:0.5:15, v/v) and detected at 214 nm.
      The recovery of BN was greater than 94% with an intra-day relative standard
      deviation < or = 4.8% and an inter-day relative standard deviation < or = 14.6%
      at any studied level. Studies of drug stability during sample storage at -20
      degrees C and at +4 degrees C did not show any significative degradation of BN.
      This method was successfully applied to explore the overdose state of heroin
      dependent subjects treated by high-dose BN.

PMID- 9777604
TI  - Analysis of brefeldin A and the prodrug breflate in plasma by gas chromatography
      with mass selective detection.
AB  - Breflate is a water soluble prodrug developed to facilitate parenteral
      administration of the investigational antineoplastic agent brefeldin A (BFA).
      Previously, using analytical methods based upon reversed-phase high performance
      liquid chromatography (HPLC) with low wavelength UV detection or gas
      chromatography (GC) with electron capture detection following derivatization with
      heptafluorobutyrylimidazole, it was demonstrated that breflate undergoes rapid
      and efficient conversion to BFA following bolus i.v. injection in mice and dogs.
      However, plasma concentrations of the drug and prodrug achieved during the
      administration of nontoxic doses of breflate to beagle dogs as a 72 h continuous
      i.v. infusion were undetectable (< 0.1 microgram ml-1) by these methods. The
      sensitivity and specificity required for therapeutic drug level monitoring were
      achieved by GC with selected-ion mass spectrometry (MS) detection. Breflate, BFA
      and 1-eicosanol, the latter added to the sample as an internal standard (IS),
      were extracted from plasma into tert-butyl methyl ether (TBME) and esterified
      with trifluoroacetic anhydride. Methanol was added to the reaction mixture to
      effect the convenient removal of excess reagent as the volatile methyl ester
      during evaporation of the solvent. The residual material was analyzed directly
      upon reconstitution by capillary GC with automated splitless injection. Electron
      ionization (70 eV) MS detection was performed by sequentially scanning ions at
      m/z 58, 202 and 325. The lowest concentration of either analyte quantified with
      acceptable reproducibility, as defined by an inter-day R.S.D. of about 20%, was
      near 10 ng ml-1 in plasma using a sample volume of 100 microliters. The assay has
      proven to be sufficiently sensitive, specific and reproducible for the routine
      analysis of pharmacokinetic specimens acquired during IND (investigational new
      drug)-directed toxicology studies in dogs.

PMID- 9777605
TI  - Liquid chromatographic determination of biotin in multivitamin-multimineral
      tablets.
AB  - A reproducible reverse phase high pressure liquid chromatography (RP-HPLC) method
      for the determination of biotin in multivitamin-multimineral tablets has been
      developed and validated. This method involves reverse phase separation of the
      component monitored by absorbance at 200 nm wavelength. The method has excellent
      precision and accuracy with S.D. 0.83 and 2.9%, respectively. The established
      linearity range was 0.5-2 micrograms ml-1 (r2 > 0.9999). The recovery of biotin
      from spiked placebo was > 97% over the linear range. The extraction procedure is
      simple and the HPLC conditions separate biotin from its degradation products and
      excipients. The method has been successfully used in determining biotin content
      in 4 brands of commercially available multivitamin-multimineral tablets.

PMID- 9777606
TI  - A kinetic enzyme immunoassay for the quantitation of antibodies to a humanized
      monoclonal antibody in human serum.
AB  - A kinetic enzyme immunoassay was developed and validated to quantitate human
      antibodies to the humanized monoclonal antibody CAMPATH1-1H (C1H) in human serum.
      The assay was configured using C1H-coated 96-well plates which were blocked with
      bovine serum albumin, and incubated with dilutions of human serum containing anti
      C1H antibody. Antibody was detected using biotinylated C1H followed by
      streptavidin-conjugated alkaline phosphatase and p-nitrophenyl phosphate.
      Absorbance data were collected for 10 min, and mOD min-1 data were exported to
      MultiCalc data analysis software. A 4-parameter logistic-log algorithm was shown
      to model the data through the range of the standard curve within 15% of nominal
      values. The overall assay performance coefficient of variation by ANOVA was 9.2%.
      The lower limit of detection was defined at 160 Units ml-1. The anti-idiotype
      antibody standard stock solution is stable at 4 degrees C and at -80 degrees C
      for at least 11 months in buffer. The anti-idiotype antibody controls are stable
      for at least seven freeze-thaw cycles and at least 6 months in human serum stored
      at -20 degrees C. A strategy was devised by which to establish the specific
      antibody potency for any given batch of anti-C1H antibody standard relative to
      the Reference Standard. This EIA has been used to quantify and characterize anti
      C1H antibody in human serum in support of clinical safety and efficacy studies.

PMID- 9777607
TI  - Comparison of classification approaches applied to NIR-spectra of clinical study
      lots.
AB  - NIR-spectroscopy combined with pattern recognition approaches is applied to
      classify samples of clinical study lots in the pharmaceutical industry. The
      performance of linear discriminant analysis (LDA), quadratic discriminant
      analysis (QDA) and K-nearest neighbour (KNN) method is evaluated on a tablet data
      set and a capsule data set. To establish a classification model a strategy is
      followed, which is described in this work. Frequently, in the pharmaceutical
      industry, several batches of the same clinical study lot are produced. We tested
      whether it is possible to merge several batches in one class for modelling or,
      instead, whether it is necessary to model each batch individually.

PMID- 9777608
TI  - Isolation and identification of a metabolite of cidofovir from rat kidney.
AB  - Cidofovir is an acyclic nucleotide analog with potent and broad-spectrum
      antiviral activity against adenoviruses and herpesviruses including
      cytomegalovirus (CMV). Cidofovir undergoes intracellular phosphorylation by host
      enzymes to cidofovir phosphate and cidofovir diphosphate (the active form). An
      unidentified metabolite has been observed previously in rat tissues and in urine
      of rabbits, rats and monkeys dosed with cidofovir. In the present study, this
      metabolite was isolated from rat kidney following an intravenous dose of 100 mg
      kg-1 cidofovir. The metabolite (metabolite I) was separated from cidofovir and
      impurities using extraction on anion-exchange resin followed by preparative
      normal and reversed-phase high-performance liquid chromatography (HPLC). The
      isolated metabolite I was subjected to proton, 13C and phosphorus nuclear
      magnetic resonance (NMR) and matrix-assisted laser desorption/ionization mass
      spectroscopy, and confirmed to be cidofovir-phosphocholine. The uptake of
      cidofovir by rat kidney was saturated at an intravenous dose of 100 mg kg-1,
      probably as a result of saturation of the renal tubular secretion pathway.
      However, the relative abundance of cidofovir phosphocholine was not affected by
      dose.

PMID- 9777609
TI  - Fluorescence detection of biotin using post-column derivatization with OPA in
      high performance liquid chromatography.
AB  - A sensitive and selective high-performance liquid chromatographic method with
      post-column derivatization, using o-phthalaldehyde (OPA) and 3-mercaptopropionic
      acid (3-MPA), is described for the determination of biotin in pharmaceutical
      preparations. The use of 3-MPA gives intense fluorescent derivative and improves
      the stability of biotin fluorophore towards oxidation to the picomole level. The
      fluorophore was detected at 453 nm (excitation at 342 nm). The calibration graph
      was linear for 20-200 ng per injection. The detection limit of biotin under these
      conditions was about 10 ng per injection. The RSDs were 1.9-3.4%. This method
      could be applied to pharmaceutical preparations without interference of other
      compounds.

PMID- 9777610
TI  - An automated method for the determination of subnanogram concentrations of
      eprinomectin in bovine plasma.
AB  - Eprinomectin is a potent anthelmintic compound that kills certain parasitic
      nematodes and arthropods of cattle. A sensitive and automated bioanalytical assay
      was developed for quantitation of eprinomectin in bovine plasma in support of
      clinical development of eprinomectin for use in all classes of cattle. This assay
      determined the concentration of eprinomectin in plasma by reversed-phase high
      performance liquid chromatography (HPLC) with fluorometric detection. Plasma
      sample preparation included liquid extraction performed by the Packard MultiPROBE
      robotics workstation, followed by solid phase extraction performed by the Gilson
      ASPEC XL automated workstation. The HPLC assay included automated pre-column
      derivatization with a fluorogenic reagent system which included trifluoroacetic
      anhydride and N-methylimidazole as the catalyst. This reversed-phase
      chromatographic analysis was based on the fluorescence detection of derivatized
      eprinomectin and an internal standard, L-648 548, which was similarly derivatized
      by the fluorogenic reagents. The assay was automated and validated for two
      concentration ranges of 0.05-10 and 0.5-200 ng ml-1. The lower limit of
      quantitation of eprinomectin in plasma was 0.05 ng ml-1. The %RSD of the assay
      was 10% or better at all concentrations. This automated analysis of eprinomectin
      was used for high-throughput clinical assays with acceptable accuracy and
      precision.

PMID- 9777611
TI  - Trace iron determination in aminoisophthalic acid using differential-pulse
      cathodic stripping voltammetry at carbon paste electrodes.
AB  - Application of differential-pulse cathodic stripping voltammetry using a carbon
      paste electrode (consisting of carbon powder and liquid paraffin) have been
      investigated for trace determination of iron in 5-aminoisophthalic acid (AIPA).
      Samples were dissolved in 1 M HC1, pH was adjusted to 4-5 after addition of EDTA.
      Voltammetric measurements were performed after filtration. No sample
      decomposition (mineralization) was necessary. The method showed a good linearity
      between current and concentration from 3 x 10(-7) to 5 x 10(-5) mol dm-3 of iron,
      with a detection limit of 3 x 10(-7) mol dm-3 (resp. 1 ppm in solid AIPA). The
      results agreed well to those obtained by atomic absorption spectrometry (AAS)
      using electrothermic atomisation. For AAS measurement, however, microwave
      digestion of samples was necessary.

PMID- 9777612
TI  - The determination of trifluoroacetic acid in rat milk samples by 19F-NMR
      spectroscopy and capillary gas chromatography.

PMID- 9777613
TI  - Value of pharmaceutical sciences.

PMID- 9777614
TI  - Vulvar disorders in prepubertal girls. A literature review.
AB  - OBJECTIVE: To review and discuss vulvar disorders in prepubertal girls. STUDY
      DESIGN: Literature review. RESULTS: Bacterial and fungal vulvitis, dermatitis,
      inflammatory dermatoses, secondary drug reactions, viral infections and a variety
      of vulvar tumors can all present as primary vulvar problems in prepubertal girls.
      In addition, systemic diseases can present with vulvar involvement. CONCLUSION:
      In order to facilitate optimal care of prepubertal girls with vulvar disorders, a
      comprehensive review of the literature is presented.

PMID- 9777615
TI  - Importance of atypical glandular cells of uncertain significance in cervical
      cytologic smears.
AB  - OBJECTIVE: To determine the clinical implications of atypical glandular cells of
      uncertain significance (AGCUS) in cervical cytologic smears. STUDY DESIGN:
      Retrospective analysis. RESULTS: Eighty-eight of 32,181 (0.27%) cervical smears
      obtained during the study period contained AGCUS. Of the 47 women with AGCUS, 16
      had intraepithelial or invasive neoplasms (34%; 95% confidence interval, 21-49%),
      including 9 low or high grade squamous intraepithelial lesions, 1 adenocarcinoma
      in situ of the cervix, 3 adenocarcinomas of the cervix, 2 adenocarcinomas of the
      endometrium and 1 adenoid basal cell carcinoma of the cervix. CONCLUSION: The
      high prevalence of cervical and endometrial neoplasia among women with the
      isolated finding of AGCUS on cervical cytologic smears warrants a thorough
      diagnostic evaluation.

PMID- 9777616
TI  - Human ejaculate. Effects on the biomechanical properties of the human
      chorioamniotic membranes.
AB  - OBJECTIVE: To determine the effects of human ejaculate on the biomechanical
      properties of the human chorioamniotic membranes. STUDY DESIGN: Equivalent strips
      of chorioamniotic membranes were obtained from 30 term, uncomplicated pregnancies
      immediately after delivery and incubated for 0, 1 and 24 hours with either
      ejaculate or pseudoamniotic fluid. Three biomechanical properties--rupture
      tension, strain to rupture and work to rupture--were compared. RESULTS: One hour
      of incubation with pseudoamniotic fluid alone did not significantly change the
      membrane biomechanical parameters, but these parameters were reduced after one
      hour of exposure to ejaculate (P < .05). Twenty-four hours of incubation
      decreased all three properties in both the ejaculate and control groups without
      any significant difference between the two groups. CONCLUSION: In vitro exposure
      to human ejaculate for one hour significantly weakens the human chorioamniotic
      membranes.

PMID- 9777617
TI  - Sexual behavior changes with vulvar vestibulitis syndrome.
AB  - OBJECTIVE: To study the changes in normal sexual behavior that accompany the
      vulvar vestibulitis syndrome and to gauge an appropriate classification for the
      resulting sexual dysfunction. STUDY DESIGN: Following full medical screening,
      questionnaires were administered to assess sexual history, illness behavior and
      vulvar discomfort. Forty patients who met the criteria of vestibulitis syndrome
      composed the study cohort. RESULTS: The average duration of reported vulvar pain
      was 33 months (range, 3-240). The cohort showed no significant differences when
      compared with normative data on the sexual history form in their level of sexual
      desire, duration of intercourse or chance of female orgasm with intercourse or
      masturbation. Patients were: (1) highly likely to experience vulvar pain with
      intercourse (P < .001), (2) highly likely to have significantly reduced arousal
      potential (P < .001), (3) highly likely to complain of vulvar symptoms preventing
      intercourse from occurring (P < .001), (4) highly likely to have a reduced
      interest in intercourse and to have negative feelings toward it (P < .001); and
      (5) highly likely to refuse a partner's sexual advances (P < .001). CONCLUSION:
      In the case of vulvar vestibulitis, the most appropriate Diagnostic and
      Statistical Manual of Mental Disorders, fourth edition, classification appears to
      be sexual dysfunction due to a general medical condition.

PMID- 9777618
TI  - Lichen sclerosus. Therapy with clobetasol propionate.
AB  - OBJECTIVE: To assess the efficacy of treating lichen sclerosus with clobetasol
      propionate. STUDY DESIGN: A retrospective chart review of 81 consecutive
      symptomatic private practice and clinic patients with biopsy-proven lichen
      sclerosus were included. All subjects' punch biopsies, baseline histories and
      physical examinations were reviewed by the same examiner. Each subject's
      symptomatology and responses to previous treatment modalities were recorded. A
      standard regimen of 0.05% clobetasol propionate cream was initiated. Subjects
      were reevaluated at three months and asked to rate the improvement of symptoms.
      Follow-up examinations were conducted 6-12 months later on 36 subjects.
      Descriptive statistics and chi 2 analyses were performed. RESULTS: The mean age
      of subjects was 54 +/- 15.5 years (range, 15-86), and the average duration of
      treatment prior to clobetasol use was 6 +/- 6.9 years (range, 0.5-29). Twenty
      seven subjects did not complete the study or were lost to follow-up. The average
      subject had tried 2.25 treatment modalities (range, 1-13). The most common
      symptoms were pruritus (98%) and irritation (61%), with complaints of burning and
      dyspareunia. Most subjects (76%) had labial involvement, with concomitant
      involvement of the clitoris (70%), perineum (68%) and perianus (32%). The
      majority (88%) of subjects had a primary lesion of white and crinkled tissue.
      With clobetasol, 77% of subjects had complete remission of symptoms, 18% had
      partial remission and 5% reported no change. A change in clinical appearance was
      noted for the complete-remission (32%) and partial-remission groups (46%). Twenty
      two percent revealed no change. CONCLUSION: Clobetasol propionate cream is
      recommended for treatment of lichen sclerosus, with a 77% chance of complete
      remission of symptoms and a 47% chance of improvement in the clinical appearance
      of the vulva. Women may have to continue to use clobetasol as needed after
      finishing a base treatment course.

PMID- 9777619
TI  - Diagnostic accuracy of transvaginal ultrasound in detecting free pelvic fluid.
AB  - OBJECTIVE: To evaluate the diagnostic accuracy of transvaginal ultrasonography in
      detecting and measuring free pelvic fluid. STUDY DESIGN: Eighty-two patients
      undergoing diagnostic or therapeutic laparoscopy at a tertiary care center were
      prospectively assessed before surgery by transvaginal ultrasound. Free pelvic
      fluid was measured in two ultrasonographic planes. These measurements were
      compared to the volume of fluid aspirated during laparoscopy. RESULTS: The mean
      volumes reported for transvaginal ultrasound were significantly lower than those
      observed at laparoscopy (mean milliliters +/- SEM, 2.54 +/- 0.5 versus 9.42 +/-
      1.3, P < .001). The smallest volume of free pelvic fluid that was consistently
      detected by ultrasound was 8 mL. Whenever no fluid or < 1 mL was detected by
      transvaginal ultrasound, a small volume of fluid was found at laparoscopy (mean
      milliliters +/- SEM, 1.6 +/- 0.47). The sensitivity of transvaginal ultrasound
      was 83% and specificity was 69%. CONCLUSION: Transvaginal ultrasound is a
      sensitive method of detecting the presence of > 8 mL of free pelvic fluid and
      therefore is an important diagnostic tool in the assessment of pelvic pathology
      associated with increased peritoneal fluid.

PMID- 9777620
TI  - Drug dependence during pregnancy. Effect of an on-site support group.
AB  - OBJECTIVE: To examine the clinical and economic efficacy of an on-site support
      group for drug-abusing pregnant women enrolled in an urban, hospital-based
      obstetric clinic. STUDY DESIGN: Maternal and neonatal outcomes and medical cost
      data were compared for drug-abusing pregnant women who attended (n = 54) and did
      not attend (n = 67) a weekly substance abuse support group in the obstetric
      clinic. RESULTS: Clinical and economic outcomes were more favorable for support
      group attenders than nonattenders. Specifically, infants of support group
      attenders had higher birth weights and better 1-minute Apgar scores. In addition,
      average short-term medical care costs were nearly $1,000 (maternal) and > $1,500
      (infant/neonatal) lower for support group attenders as compared to nonattenders.
      CONCLUSION: Support group attendance was associated with short-term clinical and
      economic benefits that are likely to translate into longer-term cost savings. The
      findings suggest that a weekly substance abuse support group can provide low
      cost, well-accepted and effective therapeutic services for this high-risk
      population of women.

PMID- 9777621
TI  - Recurrent pregnancy loss. An update.
AB  - OBJECTIVE: To comprehensively review causes of recurrent pregnancy loss and the
      currently applied methodologies for their diagnosis and management. STUDY DESIGN:
      A review article addressing pertinent issues on the subject of recurrent
      pregnancy loss, which, by definition, is three consecutive pregnancy losses prior
      to the 20th week of gestation. RESULTS AND CONCLUSION: Diagnostic workup and
      treatment of recurrent abortion often poses a special challenge as numerous
      conclusive and nonconclusive causes have been described with varied and often
      controversial approaches for their management. While a definitive cause may not
      be discovered in a significant number of cases, among those with an identifiable
      cause, anatomic disorders are by far the most conclusively diagnosable and
      effectively treatable conditions, making their exclusion or inclusion an
      essential part of the evaluation. That up to 60% of these cases may achieve
      successful pregnancy without any intervention should receive serious
      consideration when analyzing results of studies that claim therapeutic benefits
      from treatment modalities.

PMID- 9777622
TI  - Maternal and cord plasma lipid and lipoprotein concentrations in women with and
      without gestational diabetes mellitus. Predictors of birth weight?
AB  - OBJECTIVE: To describe lipid and lipoprotein perturbations in gestational
      diabetes mellitus (GDM) and to examine the potential consequences--e.g, increased
      birth weight and increased placental lipid transfer. STUDY DESIGN: Maternal and
      cord free fatty acids (FFAs) and total, very low density lipoprotein (VLDL), low
      density lipoprotein (LDL), high density lipoprotein (HDL) (and maternal HDL2 and
      HDL3), triglyceride (TG), and cholesterol and dietary intake were determined for
      women with diet-treated GDM and for healthy pregnant women with normal glucose
      tolerance. RESULTS: Women with GDM had higher hemoglobin A1c than controls, while
      body weight gain was significantly lower for women with GDM as compared to
      controls. Plasma and lipoprotein TG concentrations were greater for women with
      GDM, and although plasma FFAs were higher in women with GDM versus controls, the
      difference was not significant. No differences were observed between groups with
      respect to maternal plasma or lipoprotein cholesterol. Cord plasma and
      lipoprotein lipids were similar between groups; with the exception of VLDL + LDL
      TG, which was lower in women with GDM. In controls, there were significant
      correlations between maternal plasma TG and cord FFAs; maternal HDL2 cholesterol
      and cord plasma cholesterol; and maternal plasma TG, maternal HDL2 cholesterol,
      cord FFAs, and infant birth weight. In GDM, maternal plasma cholesterol and cord
      VLDL + LDL cholesterol correlated. There were no significant correlations between
      maternal or cord lipids and infant birth weight in women with GDM. CONCLUSION:
      Hypertriglyceridemia, rather than hypercholesterolemia, is a feature of GDM.
      However, elevations in maternal plasma and lipoprotein TGs in women with GDM were
      not related to fetal lipid concentrations or infant birth weight.

PMID- 9777623
TI  - Transvaginal ultrasonographic diagnosis of uterine septa.
AB  - OBJECTIVE: To ascertain the sensitivity of transvaginal ultrasound as a screening
      tool in diagnosing patients with uterine septa. STUDY DESIGN: In this
      descriptive, retrospective study, the medical records of all patients who had
      hysteroscopic resection of uterine septa between 1990 and 1996 were reviewed.
      Specific preoperative imaging techniques were noted, and the sensitivity of
      transvaginal ultrasonography in correctly identifying the septum was calculated.
      RESULTS: During the seven-year period, 27 of 39 total patients undergoing
      hysteroscopic metroplasty had preoperative transvaginal ultrasonography. Twenty
      two of the 27 ultrasonograms correctly identified the uterine septum, for a
      sensitivity of 81%. CONCLUSION: This was the largest study to date that
      specifically assessed the sensitivity of transvaginal ultrasonography as a
      reliable method of diagnosing uterine septa. It appears justifiable to use it as
      the initial screening tool for an accurate evaluation of uterine septa.

PMID- 9777624
TI  - Diagnosing ovarian torsion with computed tomography. A case report.
AB  - BACKGROUND: The diagnosis of adnexal torsion is difficult to make on the basis of
      symptoms, physical findings or radiologic techniques. Unfortunately, delayed
      intervention can lead to irreversible damage and loss of the adnexa. This report
      describes a finding seen on computed tomography (CT) that may increase suspicion
      of the diagnosis of ovarian torsion. CASE: A 21-year-old woman was admitted with
      constant abdominal pain and a tender retrouterine mass. Ultrasound failed to
      provide a definitive diagnosis. CT showed a central, hypodense area consistent
      with fat and surrounded by a shell of intermediate density. At laparotomy the
      patient was found to have a necrotic left adnexa due to torsion. Bisection of the
      adnexal mass confirmed a dermoid cyst with overlying edematous ovarian cortex.
      CONCLUSION: The observation of a round, hypodense central lesion (dermoid cyst)
      surrounded by thickened, edematous ovarian cortex on CT is a finding that may aid
      in the diagnosis of adnexal torsion. The finding is a thickened shell of ovarian
      cortex surrounding a central mass that has caused the torsion; in this case it
      was a dermoid cyst.

PMID- 9777625
TI  - Lower extremity paralysis after operative laparoscopy from conversion disorder. A
      case report.
AB  - BACKGROUND: Neurologic complications are rarely associated with laparoscopic
      procedures, and most nerve injuries are transient palsies. We present the first
      case of paraplegia following gynecologic laparoscopy. CASE: A 34-year-old woman,
      gravida 2, para 0-1-1-0, with long-standing infertility, underwent an
      uncomplicated laparoscopic ovarian cystectomy for a persistent ovarian
      cystadenoma. In the immediate postoperative period, the patient developed
      bilateral lower extremity paralysis. She regained her sensorimotor function in
      one extremity within hours, while both motor and sensory functions, but not
      proprioception, were deficient in the other extremity in a pattern of
      distribution that was inconsistent and paradoxical. Diagnostic studies to
      evaluate the patient's central and peripheral nervous systems and evoked sensory
      potentials were all normal. The patient's indifference to her persistent yet
      paradoxical neurologic deficits was a clue to her diagnosis. In the absence of an
      organic lesion to account for the patient's symptoms, the diagnosis of conversion
      disorder was made. CONCLUSION: Neurologic complications following laparoscopy are
      rare, generally involving nerve palsies from local injury. This is the first
      report of lower extremity paralysis after laparoscopy. Although conversion
      disorder is rare, it may occur in the gynecologic setting owing to its prevalence
      in women and especially in the presence of underlying affective disorders.

PMID- 9777626
TI  - Isolated torsion of the fallopian tube. A case report.
AB  - BACKGROUND: While torsion of the adnexa is relatively common, isolated torsion of
      the fallopian tube alone remains a rare occurrence. Diagnosis and surgical
      intervention are often delayed. CASE: A 38-year-old woman presented with acute
      lower right abdominal pain initially managed as renal colic. She returned to the
      emergency department three days later. After surgical consultation, a computed
      tomography scan and ultrasound showed a cystic pelvic mass with normal ovarian
      flow studies. Ultimately, the gynecology team performed laparoscopy with the
      suspicion of intermittent adnexal torsion. A 6 x 8-cm, twisted, dusky purple
      right fallopian tube was noted. A laparoscopic salpingectomy was performed.
      CONCLUSION: In the differential diagnosis of acute lower abdominal pain, isolated
      torsion of the fallopian tube should be considered. A timely diagnosis and
      surgical intervention may allow preservation of the tube. Even when irreversible
      damage has occurred, laparoscopic management is recommended.

PMID- 9777627
TI  - Placenta previa percreta involving the left broad ligament and cervix. A case
      report.
AB  - BACKGROUND: Placenta previa percreta with invasion of the broad ligament and
      uterine cervix is an extremely rare condition and carries high maternal and fetal
      morbidity and mortality. CASE: A 39-year-old, multiparous woman with two previous
      cesarean sections presented in active labor at term with placenta previa percreta
      involving the left broad ligament and cervix. The patient was managed by
      antepartum diagnosis of placenta previa accreta, supracervical hysterectomy, and
      blood transfusion. CONCLUSION: This case was managed consistent with the
      literature, and favorable maternal and fetal outcomes were achieved.

PMID- 9777628
TI  - Carcinoid tumor of the uterine corpus. A case report.
AB  - BACKGROUND: Carcinoid tumors are neoplasms of neuroendocrine origin that rarely
      affect the genital tract. CASE: A 75-year-old woman underwent hysterectomy and
      bilateral adnexectomy due to vaginal bleeding and uterine pathology (leiomyoma,
      cervical low grade squamous intraepithelial lesions and endometrial hyperplasia
      on ultrasound). Pathologic examination of the specimen disclosed a uterine corpus
      carcinoid tumor. The patient had been taking tamoxifen for adjuvant treatment of
      breast cancer diagnosed and treated seven years before. CONCLUSION: A review of
      the literature revealed one case of carcinoid tumor of the uterine wall. There
      does not appear to be any relationship between tamoxifen and the carcinoid tumors
      reported.

PMID- 9777629
TI  - Uniqueness and redundancy in GABA production.
AB  - GABA is present in organisms belonging to at least four of the five kingdoms. It
      acts as a neurotransmitter, a paracrine signaling molecule, a metabolic
      intermediate, or a trophic factor. In mammals, GABA synthesis depends on two
      forms of the enzyme glutamic acid decarboxylase--GAD65 and GAD67--that may serve
      distinctive functions within GABA-producing cells. The two GADs derive from two
      genes, which are differentially regulated, though nearly every GABA-producing
      cell contains both forms of GAD. GAD67 predominates early in development and
      after neuronal injury, consistent with a possible role in producing GABA for
      trophic use. In the embryo, GAD67 transcripts also undergo alternative splicing,
      which gives rise to truncated forms. In the mature neuron, GAD67 is present in
      both terminals and the cell body, where it may subserve a nonsynaptic,
      intracellular GABA pool. In contrast, GAD65 is usually expressed later in
      development and is primarily localized to nerve terminals. GAD65 enzymatic
      activity is more subject to regulation by cofactor binding and neuronal activity,
      consistent with its involvement in the production of synaptic GABA. Thus, while
      both GAD67 and GAD65 mediate the synthesis of GABA, their unique distributions
      and expression patterns suggest divergent functional roles.

PMID- 9777630
TI  - Are GAD65 and GAD67 associated with specific pools of GABA in brain?
AB  - Brain contains at least two pools of gamma-aminobutyric acid (GABA), the
      transmitter pool and the so-called metabolic pool. To a large extent these pools
      may reflect the presence of GABA in different intracellular compartments, as
      immunocytochemical studies show that GABA is not localized mainly in terminals
      but is distributed throughout neurons. An interesting issue is the extent to
      which the two major forms of glutamate decarboxylase (GAD65 and GAD67) are
      specialized to synthesize GABA for these pools. Although GAD65 and GAD67 differ
      significantly in several characteristics, they also have substantial similarities
      and interactions, and the presence of individual forms of GAD in certain cell
      types is consistent with the idea that GAD65 and GAD67 can each synthesize GABA
      for both pools. Substantial progress has been made in understanding the
      regulatory properties of GAD, but the available data provide little indication of
      how differences between the forms might enable each to serve the demands for GABA
      synthesis in a specific pool.

PMID- 9777631
TI  - Partial deafferentation of the developing rat spinal cord delays the spontaneous
      repression of GAD67 mRNAs in spinal cells.
AB  - Early and ubiquitous detection of GABA in the rat spinal cord before the
      occurrence of synaptogenesis has led to the concept of a neurotrophic role of
      GABA, in addition to a promoting effect on neurite extension and
      neurodevelopment. The aim of this study was to further establish, in vivo,
      evidence for a link between the maturation of spinal cord innervation and the
      regulation of several isoforms of the synthetic enzymes of GABA, the glutamic
      acid decarboxylases GAD65, GAD67, and EP10, the embryonic truncated form of
      GAD67. Neonatal capsaicin treatment was used to induce a specific loss of
      afferent fibers (unmyelinated C fibers, thin myelinated fibers A delta) to the
      dorsal horn. The regulation of various GAD mRNAs was investigated using sensitive
      techniques such as RT-PCR and in situ hybridization. The sensitivity of the
      methods was further enhanced by the use of a gaseous detector (beta-imager) to
      quantitate the mRNAs species. After neonatal capsaicin treatment, higher levels
      of GAD67 mRNA were detected transiently during the postnatal development of the
      rat spinal cord. A maximum two-fold increase of GAD67 mRNA was found on the day
      following the capsaicin injection and reached control values within 3 weeks. In
      contrast, GAD65 mRNA levels remained low and were unaffected by the treatment,
      and EP10 was not detected. In addition, we have found a similar upregulation,
      with the same time course, of the cytoskeletal protein beta-actin. The capsaicin
      induction of mRNA synthesis was, however, two-fold greater for beta-actin than
      for GAD67. Moreover, since this upregulation of GAD67 mRNA coincides with the
      sprouting of unaffected afferent fibers and of 5HT axons, one can hypothesize
      that GAD67 participates in the structural plasticity occurring in reaction to the
      capsaicin-induced partial deafferentation.

PMID- 9777632
TI  - Transmitting transmitter phenotypes in brain development.
AB  - Little is known about the transmitter choice of neurons in the central nervous
      system. Recent evidence suggests that precursor cells in the mammalian neocortex
      are multipotential and generate GABAergic as well as glutamatergic neurons.
      Environmental interactions within the proliferative zone seem to specify the
      transmitter phenotype of the neurons generated by the multipotential precursor
      cells. Precursor cells are restricted in the ventricular zone of a given region
      in the forebrain and do not intermingle with precursor cells from the adjacent
      regions. They are thus exposed to distinct region-specific environmental
      influences that instruct the different neuronal phenotypes found in different
      regions of the adult brain. Amongst the factors that influence the transmitter
      choice of early neuroblasts are transmitters themselves. Activity-dependent
      mechanisms mediated by a variety of neurotransmitters and their receptors could
      be the key players in specifying neuronal phenotypes at early developmental
      stages in the ventricular zone.

PMID- 9777633
TI  - GABA-immunoreactive cells of the cortical primordium contribute to distinctly
      fated neuronal populations.
AB  - The roles of GABA during development, as either a putative neurotransmitter or a
      nonsynaptic trophic factor, are being discussed intensely in recent literature.
      We offer an anatomical framework to better understand these possible roles in the
      developing cerebral cortex. During the early development of the cerebral cortex,
      GABA-containing cells constitute an outstanding cell population in the primordial
      plexiform layer, but they later distribute into at least four compartments. These
      include (1) Cajal-Retzius cells in layer I and (2) the subplate cells. Certain of
      these GABA-containing cell groups may disappear either by ceasing their
      expression of GABA, dilution in a growing brain volume, or cell death,
      possibilities that are reviewed here. The chemical tags that characterize Cajal
      Retzius cells, both in the forming isocortex and Ammon's horn, are discussed.
      Another cell population that also belongs to the primordial plexiform layer is
      formed by (3) the tangentially migrating cells of the deep intermediate layer.
      These migrate away from the isocortical primordium to invade, and contribute
      cells to, the forming stratum oriens of the Ammon's horn. Since these cells cross
      cortical area boundaries, their tangential migration is relevant to the issue of
      cortical area specification during development. Finally, GABA-immunoreactive
      cells in the developing cortical plate are considered to be (4) the future
      GABAergic interneurons. A hypothetical mechanism is presented here to explain
      their acquisition of laminar positions, which is known to take place
      simultaneously, and with an identical "inside-out gradient," to the pyramidal
      cells generated contemporarily.

PMID- 9777634
TI  - Neural cells derived by in vitro differentiation of P19 and embryonic stem cells.
AB  - The past decade has seen great progress in understanding the key genes involved
      in GABAergic transmission. The genes for GAD, multiple subunits of the ionotropic
      GABA receptors, metabotropic GABA receptors, and GABA uptake proteins have been
      cloned. Analysis of the cloned genes has yielded a plethora of fundamental
      insights into the role of the corresponding proteins in mediating GABAergic
      signals (reviewed in Tobin et al. and Erlander and Tobin). Tools based on these
      new studies, ranging from monoclonal antibodies to gene probes, have also allowed
      detailed mapping of expression patterns in the central nervous system (CNS).
      These new studies reveal that some components of GABAergic transmission have a
      very wide distribution, being expressed by GABAergic neurons throughout the CNS.
      Others have a much more restricted pattern of expression. The highly specific
      expression of GABAergic genes poses a set of fundamental challenges to
      developmental neurobiology. What genetic mechanisms underlie these patterns of
      expression? How are complex structures such as receptors assembled? How do the
      components of a GABAergic synapse come to be localized in proximity to each other
      so as to make functional transmission possible? Cell lines that express GABAergic
      phenotypes play an important part in answering these and related questions. With
      appropriate cell lines it should be possible to manipulate genes related to the
      GABAergic phenotype in ways that shed light on these questions. Recently, work
      from several laboratories, including our own, has shown that two pluripotent cell
      lines from the mouse, the P19 embryonal carcinoma line and embryonic stem (ES)
      cells, are capable of differentiating into neuron-like cells with GABAergic
      phenotypes. Since these cell lines are highly suitable for genetic manipulation,
      they should be extremely useful for studying the relationship between GABA
      related genes and the phenotypes they encode.

PMID- 9777635
TI  - GABAA-receptor subtypes in developing brain. Actors or spectators?
AB  - Distinct GABAA-receptor subtypes, differing in subunit composition, physiology,
      and pharmacology, are expressed in fetal, neonatal, and adult brain. Their
      developmental schedule, evidenced by the differential maturation of the GABAA
      receptor subunits alpha 1, alpha 2, and alpha 5, is similar in rodents and
      primates, indicating that the regulation of receptor subtypes is conserved across
      species. "Adult" GABAA-receptors, characterized by the alpha 1-subunit
      immunoreactivity, are largely absent from fetal brain. They appear, however,
      before the onset of functional inhibitory connections, suggesting that GABAA
      receptors may play an active role in the formation of GABAergic synapses. In
      neocortex, the maturation of GABAA-receptor subtypes is governed by an intrinsic
      program, leading to an area- and lamina-specific distribution as early as E20 in
      rats. In primary somatosensory and visual areas, this pattern is influenced
      postnatally by the ingrowing thalamocortical projection, a process that can be
      prevented experimentally by lesioning the thalamus at birth. Altogether, the
      expression of GABAA-receptor subtypes in developing brain reflects the changing
      functional needs of neurons during differentiation, the formation of inhibitory
      circuits, and the emergence of functionally distinct brain compartments.

PMID- 9777636
TI  - Differentially expressed GABAA-receptor subunits result in structurally and
      functionally receptor assemblies following excitatory afferent synaptic
      transmission.
AB  - Cerebellar granule cells isolated from postnatal day 7 rat pups are ideal for
      studying epigenetic events associated with the regulation of neuronal gene
      expression. These cultures contain from 90 to 95% glutamatergic granule cells and
      express mRNAs encoding a variety of ionotropic and metabotropic glutamate
      receptors as well as virtually all of the GABAA-receptor subunit mRNAs to
      different extents. A unique feature of this culture system is that the neurons
      undergo time-dependent maturation changes in vitro that mimic many of the
      characteristics of these receptors occurring in vivo. Granule cell cultures in
      vitro require depolarizing concentrations of KCl for long-term growth and
      survival. Both N-methyl-D-aspartate (NMDA) and GABA have been reported to exert
      trophic actions on these cells replacing the requirement for maintaining the
      cultures in high KCl. Cerebellar granule cells maintained under different
      conditions in vitro can be induced to alter their patterns of maturation, as
      indicated by the different temporal changes in gene expression of receptor
      subunit mRNAs and proteins. The focus of the current studies is the effect of
      NMDA afferent synaptic signaling on the changes in mRNA content and functional
      properties of GABAA receptors and how this may relate to comparable changes shown
      to occur in vivo.

PMID- 9777637
TI  - Developmental expression of cerebellar GABAA-receptor subunit mRNAs. Nature
      versus nurture.
AB  - Recent studies have demonstrated that many of the mRNAs encoding GABAA-receptor
      subunits in the cerebellum exhibit distinct temporal profiles of expression. The
      levels of six of these subunit transcripts increase severalfold in the second
      week of postnatal ontogeny. Findings from a variety of experimental systems
      suggest that the onset and increases in subunit mRNA expression are mediated by
      the interaction of genetic and epigenetic programs. The initiation of subunit
      mRNA expression occurs relatively early in cellular maturation and may be
      directed by intrinsic mechanisms. However, the levels of expression attained in
      adult animals may be controlled by extrinsic signals received by neurons during
      the postnatal maturation process.

PMID- 9777638
TI  - Early developmental modulation of GABAA receptor function. Influence on adaptive
      responses.
AB  - If GABA is serving a trophic role during early brain development, before taking
      on its function as a neurotransmitter, interference with the function of GABA
      during this period should have a profound influence on neural organization. We
      have addressed this hypothesis by evaluating the effects of exposing rat fetuses
      to diazepam (DZ), a positive modulator of GABA at the GABAA receptor, over
      gestation days 14 to 20. Studies have shown that adult rats exposed in utero to
      DZ over this developmental period make inappropriate behavioral responses and
      have altered neural and hormonal responses to environmental stimuli that threaten
      the organism's stability and homeostasis. Thus, the early exposure led to altered
      adaptive responses. These effects of the early exposure did not become apparent
      until late in adolescent development. Furthermore, specific behavioral and neural
      responses to environmental challenges normally emerge over adolescent
      development. Other studies have shown that the GABAA receptor in adult brains is
      responsive to environmental challenges. Thus, we hypothesize that early
      modulation of the action of GABA mediated via the GABAA receptor interfered with
      the neural organization of adaptive responses.

PMID- 9777639
TI  - Effects of gamma-aminobutyric acid (GABA) on synaptogenesis and synaptic
      function.
AB  - The correct establishment and function of synapses depend on a variety of
      factors, such as guidance of pre- and postsynaptic neurons as well as receptor
      development and localization. gamma-Aminobutyric acid (GABA) has a pronounced
      effect on these events and elicits differentiation of neurons; that is, GABA acts
      as a trophic signal. Accordingly, activating preexisting GABA receptors, a
      trophic GABA signal enhances the growth rate of neuronal processes, facilitates
      synapse formation, and promotes synthesis of specific proteins. Transcription and
      de novo synthesis are initiated by the GABA signal, but the intracellular link
      between GABA receptor activation and DNA transcription is largely unknown. GABA
      also controls the induction and development of functionally and pharmacologically
      different GABAA receptor subtypes. The induced receptors are likely to be
      inserted only into the synaptic membrane domain. However, this ability to target
      the induced GABAA receptors is probably coupled to the maturation of neurons and
      not to the action of GABA per se. The induced GABAA receptors apparently mediate
      a pronounced inhibition of neurotransmitter release, whereas other subtypes of
      GABAA receptors may be modulatory rather than inhibitory.

PMID- 9777640
TI  - GABA as a trophic factor for developing monoamine neurons.
AB  - GABA exerts a variety of trophic influences on developing brain cells, as
      reviewed in this issue. During early stages of brain development, GABAergic axons
      course through regions where other neurotransmitter phenotypes are being
      generated. This raises the question of whether GABA may influence the ontogeny of
      these neurotransmitter systems in the embryonic brain. The brainstem provides a
      good example of this relationship, since GABAergic axons pass through the anlage
      of the developing raphe nuclei when serotonergic (5-HT) neurons are just
      beginning to differentiate and migrate away from the ventricular zone. Evidence
      that GABA regulates development of these and adjacent noradrenergic neurons has
      recently been obtained using embryonic brainstem cultures, which contain
      differentiating 5-HT, tyrosine hydroxylase (TH), and GABA neurons. These cultures
      also express multiple GABAA-receptor subunits that form functional GABAA/Cl-
      channels. GABAA receptor ligands produce differential effects on survival and
      growth of monoamine (5-HT, TH) and GABA neurons, and on expression of GABAA
      subunits in these cultures. These findings provide evidence that GABA can
      selectively regulate development of neurons of different neurotransmitter
      phenotypes, as well as developmental expression of its own receptors, and suggest
      that in utero exposure to GABAA receptor ligands could produce imbalances in
      monoaminergic versus GABAergic neurotransmission in the developing brain.
      Dieldrin, an organochlorine pesticide that acts as a GABAA antagonist, has potent
      effects on survival, and neurite outgrowth by 5-HT neurons, and GABAA subunit
      expression in brainstem cultures. Thus, maternal exposure to organochlorine
      pesticides could pose a risk to fetal brain development, especially during the
      first trimester of pregnancy.

PMID- 9777641
TI  - GABA as a developmental neurotransmitter in the outer plexiform layer of the
      vertebrate retina.
AB  - GABA is present in certain retinal neurons before synapses are formed, and it has
      a variety of effects on the developing retina. Its exact role in retinal
      maturation is not clear; however, there is growing evidence from rabbit retina
      that neonatal horizontal cells produce GABA within the outer retina, which in
      turn is necessary for normal synapse formation of photoreceptors. In addition to
      its classic role as an inhibitory transmitter, GABA in the neonate increases
      intracellular calcium levels in selected cells. This latter property is lost
      during postnatal development, along with a general decrease in the level of
      expression of both pre- and postsynaptic GABAergic markers and a decrease in the
      number of GABAergic neurons. The adult GABAergic circuitry in adult retina may
      represent a restricted, perhaps simplified version of the more complex and
      diversified interactions of the GABA system during development.

PMID- 9777642
TI  - GABA as a developmental signal in the inner retina and optic nerve.
AB  - Gamma-aminobutyric acid (GABA) acts as an inhibitory neurotransmitter in the
      mature vertebrate retina, where it is localized predominantly in amacrine cells,
      and to a lesser extent in other cell types. During development, GABA is expressed
      transiently in additional cells, including retinal ganglion cells and horizontal
      cells. Elements of the GABA system, including GABA uptake and release mechanisms
      and GABA receptors, are also expressed early in retinal development, well in
      advance of the onset of visual function. The GABA transporter is a major
      component of the GABA system in the mature retina, and is most likely responsible
      for GABA release early in development, prior to the establishment of vesicular
      synaptic transmission. GABA, produced by amacrine cells and retinal ganglion
      cells, may serve a developmental role in the establishment of circuitry in the
      retinal inner plexiform layer and may also be involved in the formation of
      appropriate central connections by retinal ganglion cell axons.

PMID- 9777643
TI  - Physiological functions of GABA-induced depolarizations in the developing rat
      spinal cord.
AB  - Gamma-aminobutyric acid (GABA) is one of the principle inhibitory
      neurotransmitters in the mature spinal cord. It effectively suppresses synaptic
      transmission by mechanisms of postsynaptic and presynaptic inhibition. The
      function of GABA is less well understood early in spinal cord development, when
      the amino acid is transiently expressed in most neurons, and it depolarizes
      instead of hyperpolarizes neurons. This article reviews the possible
      physiological roles of GABA in modulating synaptic transmission, promoting
      neuronal development, and regulating neuronal pH during early stages of spinal
      cord differentiation. It is proposed that despite its depolarizing action, GABA
      acts as an inhibitory neurotransmitter that may also function as a neurotrophic
      agent.

PMID- 9777644
TI  - GABA excites immature CA3 pyramidal cells through bicuculline-sensitive and 
      insensitive chloride-dependent receptors.
AB  - Intracellular and patch clamp recording techniques were used to investigate the
      role of GABA in immature CA3 hippocampal neurons. During the first postnatal week
      spontaneous GABA release was detected as spontaneous ongoing synaptic potentials
      (SPSPs) or giant depolarizing potentials (GDPs). GDPs were generated at regular
      intervals and regulated by ionotropic glutamate receptors (GluRs), whereas SPSPs
      occurred randomly and were unaffected by ionotropic GluRs. Both GDPs and SPSPs
      were positively modulated by metabotropic GluRs through cyclic AMP-dependent
      protein kinase. Moreover GABA controlled its own release through GABAA and GABAB
      receptors, probably localized on GABAergic nerve terminals. At this developmental
      stage, GABA depolarized CA3 pyramidal cells through two distinct classes of
      chloride-permeable receptors: bicuculline sensitive and insensitive,
      respectively. The bicuculline-insensitive responses were blocked by picrotoxin in
      a noncompetitive way. Whole-cell GABA currents, recorded in the presence of
      bicuculline, had a slower desensitization rate and faster recovery from
      desensitization. In excised outside-out patches, in the presence of bicuculline,
      GABA activated single-channel currents with conductances of 14, 22, and 31 pS.
      These values were similar to those obtained when GABA was applied in the absence
      of bicuculline. Interestingly, GABA responses obtained in the absence of
      bicuculline, were sensitive to the blocking effect of zinc, whereas bicuculline
      resistant responses were almost unaffected by this divalent cation. Expression of
      different subunits in native receptors (particularly of the alpha and rho type)
      may account for the functional differences observed in the present experiments.
      Activation of bicuculline-insensitive receptors would strengthen and prolong the
      depolarizing action of GABA, thus favoring the entry of calcium through voltage
      dependent calcium channels. This calcium signal may be essential in promoting
      stabilization of synaptic contacts during a critical period of postnatal
      development.

PMID- 9777645
TI  - GABAergic cells and signals in CNS development.
AB  - GABA is formed primarily from decarboxylation of glutamate by a family of
      cytosolic and membrane-bound GAD enzymes. In the adult, GAD-derived GABA sustains
      the vitality of the central nervous system (CNS), since blockage of GAD rapidly
      leads to convulsions and death. In plants, cytosolic GAD synthesizes GABA in
      response to hormones and environmental stress. Since decarboxylation involves
      protonation, secretion of GABA serves to buffer cytosolic pH in plant cells.
      Families of GAD and GABAA receptor/Cl- channel transcripts and encoded proteins
      emerge early and seemingly everywhere during CNS development, with their
      abundance closely paralleling neurogenesis and peaking before birth. Micromolar
      GABA acts at receptor/Cl-channels to depolarize progenitor cells in the cortical
      neuroepithelium; it also elevates their cytosolic Ca2+ (Cac2+) levels. In some
      way, these effects decrease proliferation. GABA directs the migration of
      postmitotic neuroblasts at femtomolar concentrations and stimulates their random
      motility at micromolar concentrations via Ca2+ signaling mechanisms. Activation
      of GABAA receptors by micromolar GABA may limit motility via membrane
      depolarization and elevated Cac2+. These results indicate that in vitro GABA can
      affect embryogenesis of the CNS through effects on cell proliferation and
      migration. As neurons differentiate postnatally, Cl(-)-dependent depolarization
      disappears together with GABAergic Cac2+ signals. Physiologically occurring
      GABAergic signals at Cl-channels exist in tonic and transient forms. Since the
      former are found on progenitor cells while both are present in postmitotic
      neurons, mechanisms to generate transients differentiate in the latter.
      Surprisingly, tonic and transient forms of GABAergic signaling at Cl-channels are
      rapidly and smoothly interconvertible and seem to be derived from online GABA
      synthesis in a surface-accessible compartment of the membrane.

PMID- 9777646
TI  - Apoptotic cell death in retinal degenerations.
AB  - Apoptosis is a regulated mode of single cell death that involves gene expression
      in many instances and occurs under physiological and pathological conditions in a
      large variety of systems. We briefly summarize major features of apoptosis in
      general and describe the occurrence of apoptosis in the retina in different
      situations that comprise animal models of retinitis pigmentosa, light-induced
      lesions, histogenesis during development, and others. Apoptosis can be separated
      into several phases: the induction by a multitude of stimuli, the effector phase
      in which the apoptotic signal is transmitted to the cellular death machinery, the
      excecution period when proteolytic cascades are activated, and the phagocytic
      removal of cellular remnants. Control mechanisms for retinal apoptosis are only
      beginning to be clarified. Potential apoptotic signal transducers were
      investigated in our laboratory, including metabolites of arachidonic acid and
      downstream mediators of signaling molecules such as transcription factors. Work
      in our laboratory revealed an essential role of the immediate-early gene product
      c-Fos in light-induced apoptosis. c-Fos is a member of the AP-1 family of
      transcription factors and, together with other members of this family, it may
      regulate apoptosis in the central nervous system. Expression of the c-fos gene in
      the retina can be evoked by light exposure and follows a diurnal rhythm. Future
      studies will have to clarify how light can control the expression of specific
      genes, and specifically, the role of c-fos and other genes of retinal apoptosis
      including potential target genes and signaling pathways.

PMID- 9777647
TI  - The intact isolated (ex vivo) retina as a model system for the study of
      excitotoxicity.
AB  - Excitotoxicity is defined as a mode of neural cell death triggered by
      overactivation of receptors for the amino acid transmitter glutamate. There is
      considerable evidence that excitotoxicity is responsible for cell death in
      several neuropathological states, including some retinal diseases. The isolated
      retina, particularly from chick embryos, has been used extensively as an
      experimental system to characterize this process. This paper summarizes the use
      of isolated retina as a model system for studies of excitotoxicity from a
      theoretical and methodological point of view, and reviews results obtained from
      studies utilizing this system.

PMID- 9777648
TI  - Oscillatory potentials in the retina: what do they reveal.
AB  - This chapter is an overview of current knowledge on the oscillatory potentials
      (OPs) of the retina. The first section describes the characteristics of the OPs.
      The basic, adaptational, pharmacological and developmental characteristics of the
      OPs are different from the a- and b-waves, the major components of the
      electroretinogram (ERG). The OPs are most easily recorded in mesopic adaptational
      conditions and reflect rapid changes of adaptation. They represent photopic and
      scotopic processes, probably an interaction between cone and rod activity in the
      retina. The OPs are sensitive to disruption of inhibitory (dopamine, GABA-, and
      glycine-mediated) neuronal pathways and are not selectively affected by
      excitatory amino acids. The earlier OPs are associated with the on-components and
      the late OPs with the off-components in response to a brief stimulus of light.
      The postnatal appearance of the first oscillatory activity is preceded by the a-
      and b-waves. The earlier OPs appear postnatally prior to, and mature differently
      from, the later ones. The second section deals with present views on the origin
      of the OPs. These views are developed from experimental studies with the
      vertebrate retina including the primate retina and clinical studies. Findings
      favor the conclusion that the OPs reflect neuronal synaptic activity in
      inhibitory feedback pathways initiated by the amacrines in the inner retina. The
      bipolar (or the interplexiform) cells are the probable generators of the OPs.
      Dopaminergic neurons, probably amacrines (or interplexiform cells), are involved
      in the generation of the OPs. The earlier OPs are generated in neurons related to
      the on-pathway of the retina and the later ones to the off-channel system.
      Peptidergic neurons may be indirectly involved as modulators. The individual OPs
      seem to represent the activation of several retinal generators. The earlier OPs
      are more dependent on an intact rod function and the later ones on an intact cone
      system. Thus, the OPs are good indicators of neuronal adaptive mechanisms in the
      retina and are probably the only post-synaptic neuronal components that can be
      recorded in the ERG except when structured stimuli are used. The last section
      describes the usefulness of the oscillatory response as an instrument to study
      the postnatal development of neuronal adaptation of the retina. In this section
      clinical examples of of the sensitivity of the OPs for revealing early
      disturbance in neuronal function in different retinal diseases such as pediatric,
      vascular and degenerative retinopathies are also given.

PMID- 9777649
TI  - Light adaptation and sensitivity controlling mechanisms in vertebrate
      photoreceptors.
AB  - The human visual system can discriminate increment and decrement light stimuli
      over a wide range of ambient illumination; from moonlight to bright sunlight.
      Several mechanisms contribute to this property but the major ones reside in the
      retina and more specifically within the photoreceptors themselves. Numerous
      studies in retinae from cold- and warm-blooded vertebrates have demonstrated the
      ability of the photoreceptors to respond in a graded manner to light increments
      and decrements even if these are applied during a background illumination that is
      expected to saturate the cells. In all photoreceptors regardless of type and
      species, three cellular mechanisms have been identified that contribute to
      background desensitization and light adaptation. These gain controlling
      mechanisms include; response-compression due to the non-linearity of the
      intensity-response function, biochemical modulation of the phototransduction
      process and pigment bleaching. The overall ability of a photoreceptor to adapt to
      background lights reflects the relative contribution of each of these mechanisms
      and the light intensity range over which they operate. In rods of most species,
      response-compression tends to dominate these mechanisms at light levels too weak
      to cause significant pigment bleaching and therefore, rods exhibit saturation. In
      contrast, cones are characterized by powerful background-induced modulation of
      the phototransduction process at moderate to bright background intensities where
      pigment bleaching becomes significant.Therefore, cones do not exhibit saturation
      even when the level of ambient illumination is raised by 6-7 log units.

PMID- 9777650
TI  - Tear dynamics and dry eye.
AB  - Tears undergo four processes: production by the lacrimal gland, distribution by
      blinking, evaporation from the ocular surface and drainage through the
      nasolacrimal duct. Abnormalities in any of these steps can cause dry eye. There
      are two kinds of tear production, basic and reflex, which can be distinguished
      from each other by the Schirmer test with nasal stimulation. Reflex tearing is
      important because it supplies such essential components as EGF and vitamin A,
      whose deficiency may cause squamous metaplasia. There is no reflex tearing in
      Sjogren's syndrome because of destruction of the lacrimal gland. In cases of
      diminished or absent reflex tearing, topical autologous serum is the treatment of
      choice. Even when there is adequate tear production, insufficient distribution,
      such as occurs with the decreased blinking associated with the use of video
      display terminals (VDT), may cause dry eye. Any process or activity that
      suppresses blinking interferes with tear distribution. Tear evaporation increases
      under certain conditions and in some diseases. When the exposed ocular surface
      area is increased, such as in VDT work, tear evaporation increases. Meibomian
      gland dysfunction (MGD) also causes increased tear evaporation by altering the
      quality of the oily layer in tears. Tear evaporation can be suppressed by using a
      warm compresser or a humidifier, narrowing the palpebral fissure, or wearing
      protective eyeglasses. The tear clearance rate is measured by fluorescein dye
      dilution in the conjunctiva. When the tear clearance is low, inflammatory
      cytokines or preservatives accumulate in the conjunctival sac, resulting in
      ocular surface diseases. Frequent use of artificial tears without preservative is
      the key treatment. A differential diagnosis of the abnormalities of tear dynamics
      can give us a proper understanding of the pathogenesis of dry eye. With this
      knowledge, we can formulate an efficient therapeutic approach.

PMID- 9777651
TI  - The eyes of deep-sea fish. I: Lens pigmentation, tapeta and visual pigments.
AB  - Deep-sea fish, defined as those living below 200 m, inhabit a most unusual photic
      environment, being exposed to two sources of visible radiation; very dim
      downwelling sunlight and bioluminescence, both of which are, in most cases,
      maximal at wavelengths around 450-500 nm. This paper summarises the reflective
      properties of the ocular tapeta often found in these animals, the pigmentation of
      their lenses and the absorption characteristics of their visual pigments. Deep
      sea tapeta usually appear blue to the human observer, reflecting mainly shortwave
      radiation. However, reflection in other parts of the spectrum is not uncommon and
      uneven tapetal distribution across the retina is widespread. Perhaps
      surprisingly, given the fact that they live in a photon limited environment, the
      lenses of some deep-sea teleosts are bright yellow, absorbing much of the
      shortwave part of the spectrum. Such lenses contain a variety of biochemically
      distinct pigments which most likely serve to enhance the visibility of
      bioluminescent signals. Of the 195 different visual pigments characterised by
      either detergent extract or microspectrophotometry in the retinae of deep-sea
      fishes, ca. 87% have peak absorbances within the range 468-494 nm. Modelling
      shows that this is most likely an adaptation for the detection of
      bioluminescence. Around 13% of deep-sea fish have retinae containing more than
      one visual pigment. Of these, we highlight three genera of stomiid dragonfishes,
      which uniquely produce far red bioluminescence from suborbital photophores. Using
      a combination of longwave-shifted visual pigments and in one species (Malacosteus
      niger) a chlorophyll-related photosensitizer, these fish have evolved extreme red
      sensitivity enabling them to see their own bioluminescence and giving them a
      private spectral waveband invisible to other inhabitants of the deep-ocean.

PMID- 9777652
TI  - The eyes of deep-sea fish. II. Functional morphology of the retina.
AB  - Three different aspects of the morphological organisation of deep-sea fish
      retinae are reviewed: First, questions of general cell biological relevance are
      addressed with respect to the development and proliferation patterns of
      photoreceptors, and problems associated with the growth of multibank retinae, and
      with outer segment renewal are discussed in situations where there is no direct
      contact between the retinal pigment epithelium and the tips of rod outer
      segments. The second part deals with the neural portion of the deep-sea fish
      retina. Cell densities are greatly reduced, yet neurohistochemistry demonstrates
      that all major neurotransmitters and neuropeptides found in other vertebrate
      retinae are also present in deep-sea fish. Quantitatively, convergence rates in
      unspecialised parts of the retina are similar to those in nocturnal mammals. The
      differentiation of horizontal cells makes it unlikely that species with more than
      a single visual pigment are capable of colour vision. In the third part, the
      diversity of deep-sea fish retinae is highlighted. Based on the topography of
      ganglion cells, species are identified with areae or foveae located in various
      parts of the retina, giving them a greatly improved spatial resolving power in
      specific parts of their visual fields. The highest degree of specialisation is
      found in tubular eyes. This is demonstrated in a case study of the scopelarchid
      retina, where as many as seven regions with different degrees of differentiation
      can be distinguished, ranging from an area giganto cellularis, regions with
      grouped rods to retinal diverticulum.

PMID- 9777653
TI  - Oxysterols and TBARS are among the LDL oxidation products which enhance
      thromboxane A2 synthesis by platelets.
AB  - In this study, we compared the effects of normal LDL (nLDL) and oxidized LDL
      (oxLDL) on thromboxane (TXA2) release by platelets triggered by low concentration
      of thrombin, and we determined which component of oxLDL is responsible for that
      activation. After oxidation of LDL with copper sulfate, the small molecular
      weight fraction (< 10 kDa) which was high in TBARS was removed; using Amicon
      Centriprep-10 concentrator membrane. More than 67% of TBARS in the oxLDL
      preparation was found in solution while the remaining was covalently attached to
      the oxLDL particles. OxLDL contained significantly higher levels of oxysterols
      and TBARS than the nLDL. Platelets preincubated with low concentrations of oxLDL
      (33-132 micrograms protein/mL) produced significantly higher TXA2 than platelets
      preincubated with equivalent concentrations of nLDL when triggered with thrombin.
      Platelets treated with oxLDL also contained significantly higher levels of
      oxysterols than platelets treated with nLDL. Platelets preincubated with pure
      cholestanetriol (10 micrograms/mL) contained a high level of cholestanetriol in
      the membrane, and TXA2 release was significantly increased in these platelets
      compared to the control platelets. The TBARS in solution also was very potent in
      enhancing TXA2 release by thrombin-treated platelets. These results indicate that
      oxysterols and the free TBARS either in solution or covalently attached to the
      oxLDL particles are partly responsible for the stimulatory effect of oxLDL on
      TXA2 release by platelets. The present study also showed that this enhancement of
      TXA2 release was due to activation of phospholipase A2 and to the increase of
      arachidonic acid liberation from the platelet phospholipids.

PMID- 9777654
TI  - Vitamin E supplementation attenuates myointimal proliferation of the abdominal
      aorta after balloon injury in diet-induced hypercholesterolemic rabbits.
AB  - The effects of vitamin E supplementation in a dose of 450 mg/1000 g chow on the
      myointimal proliferation of the abdominal aorta after balloon injury were studied
      in 4 groups of rabbits (24 each). The animals were fed regular diet, regular diet
      plus vitamin E, 1% cholesterol-enriched diet, and 1% cholesterol-enriched diet
      plus vitamin E. Each animal underwent a balloon injury of the abdominal aorta and
      left common iliac artery after 2 weeks of feeding. The animals remained on their
      respective diets thereafter. In 8 balloon-injured and 8 sham-operated animals of
      each group, the abdominal aortas were harvested 3 days after the procedure for
      the analysis of prostacyclin and thromboxane A2 synthesis, thiobarbituric acid
      reactive substances (TBARS) levels, enzyme activities of glutathione reductase
      (GR) and glutathione peroxidase (GP) as well as reduced (GSH) and oxidized (GSSG)
      glutathione levels, 3H-thymidine uptake, cholesterol as well as vitamin E
      contents. In the other 8 balloon-injured rabbits of each group, the tissue was
      harvested 3 weeks later for the morphometric study. In dependent of high
      cholesterol feeding, the vitamin E-treated rabbits had lower aortic production of
      thromboxane B2, higher 6-keto-PGF1 alpha and higher 6-keto-PGF1 alpha/thromboxane
      B2 ratios in both procedures. The aortic TBARS levels of the rabbits treated high
      cholesterol alone were significantly higher than the other three groups in both
      procedures. Balloon injury had a trend to increase TBARS levels and had
      significantly higher 3H-thymidine uptake (each p < 0.001) than sham operation in
      each group. Vitamin E supplement to high cholesterol diet or regular chow reduced
      aortic TBARS levels (p < 0.005 and 0.01, respectively) and 3H-thymidine uptake (p
      < 0.05 and 0.01, respectively), as well as attenuated myointimal proliferation of
      the abdominal aorta and left common iliac artery after balloon injury; but only
      supplement to high cholesterol diet reached statistical significances (both p <
      0.05 compared to rabbits fed high cholesterol alone). These results suggest that
      vitamin E supplement changes prostanoid metabolism to a favorable pattern and
      reduces lipid peroxidation of the abdominal aortic wall, thus attenuates
      myointimal proliferation after balloon injury; these presentations are
      particularly obvious in diet-induced hypercholesterolemic rabbits.

PMID- 9777656
TI  - Analgesic effect of mofezolac, a non-steroidal anti-inflammatory drug, against
      phenylquinone-induced acute pain in mice.
AB  - The oral administration of mofezolac, [3,4-di(4-methoxyphenyl)-5
      isoxazolyl]acetic acid, resulted in the suppression of writhing induced by the
      intraperitoneal injection of phenyl-p-benzoquinone (phenylquinone, PQ) in mice.
      The analgesic activity of mofezolac was almost as potent as that of indomethacin,
      and more potent than that of sodium diclofenac, zaltoprofen, NS-398, and etodolac
      when their 50% effective doses were compared. The in vitro inhibitory activity of
      mofezolac against ovine cyclooxygenase (COX)-1 was also more potent than that of
      any other non-steroidal anti-inflammatory drugs (NSAIDs) tested, whereas the
      activity of mofezolac against COX-2 was relatively weak. A Western analysis
      revealed COX-1 to be constitutively expressed, whereas COX-2 was hardly expressed
      until 30 min after the PQ-injection in the peritoneal cells. Because the writhing
      terminated within 30 min after PQ-injection, the prostaglandins involved in the
      induction of writhing seem to be derived from COX-1. These data thus indicate
      that potent analgesic activity of mofezolac against the present model to be more
      closely related to its potent inhibitory activity against COX-1 but not against
      COX-2.

PMID- 9777655
TI  - PAF- and histamine-receptor antagonists lessen allergen-induced hearing
      impairment in guinea pigs.
AB  - We have demonstrated degranulation of mast cells in the endolymphatic sac as well
      as an increase in audiological threshold shift in the experimental animal models
      following antigen provocation. Mast cells, however, release such chemical
      mediators as histamine, platelet activating factor (PAF), and leukotriene due to
      an antigen-antibody reaction on the cell surface. The aim of this study was to
      clarify the major chemical mediators responsible for hearing impairment in the
      animal models following antigen provocation. Guinea pigs were actively sensitized
      with DNP-Ascaris and provoked with an injection of DNP-BSA. A significant
      audiological threshold shift was observed at 1, 10, 24, and 72 h following
      challenge with allergen. The peak shift was at 10 h; all changes were reversed
      after 7 days. This threshold shift was abolished by prior injection of either a
      histamine- or PAF-receptor antagonist to allergen, but not of a leukotriene
      receptor antagonist. Results suggest that histamine and PAF are involved in the
      hearing impairment induced by allergen exposure in the guinea pig.

PMID- 9777657
TI  - Changes in refractoriness of rabbit corpora lutea to a prostaglandin F2 alpha
      analogue, alfaprostol, during pseudopregnancy.
AB  - The responsiveness of rabbit corpus luteum to 200 micrograms of the prostaglandin
      F2 alpha (PGF2 alpha) analogue, alfaprostol, between Days 3 and 9 of
      pseudopregnancy was assessed by evaluating the decline in plasma progesterone
      after treatment with PGF2 alpha in 81 New Zealand White (NZW) rabbits. On Days 3
      5, functional luteolysis was not observed. On Days 6, 7, and 8 of
      pseudopregnancy, the number of rabbits responsive to PGF2 alpha, rose from 38% to
      71% and 83%, respectively. In the other cases, the effect of the PGF2 alpha
      analogue was transient as CL recovered in the following 2 or 3 days. By contrast,
      on Day 9 luteolysis was effective and persistent in all the animals. In rabbits
      treated on Day 9, progesterone decreased gradually from 10.6 +/- 0.7 within the
      first 6 h, but fell to 3.6 +/- 1.5 ng/mL (p < 0.01) 12 h after PGF2 alpha and to
      0.2 +/- 0.1 ng/mL (p < 0.01) 24 h later.

PMID- 9777658
TI  - Effects of tennis practice on the coincidence timing accuracy of adults and
      children.
AB  - This study examines the development of perceptuomotor processes involved in
      coincidence timing tasks according to age and experience in tennis. Tennis
      players and novices, 7, 10, 13, and 23 years of age, were tested in a coincidence
      timing task which consisted of estimating the arrival of a simulated moving
      object on a target. The effect of three different motions were analyzed: constant
      velocity, constant acceleration, and constant deceleration. Results showed that
      (1) timing accuracy improves mainly between the ages of 7 and 10 years; (2)
      tennis practice accelerates the development of timing accuracy; and (3)
      acceleration or deceleration of the moving stimulus had no effect on the timing
      accuracy of any of the tested groups, suggesting a continuous visual control of
      the trajectory. Theoretical implications for the development of perceptuomotor
      processes involved in coincidence timing tasks are discussed.

PMID- 9777659
TI  - Relative frequency of knowledge of performance and motor skill learning.
AB  - This study examined the effects of variations in relative frequency of knowledge
      of performance (KP) on acquisition, retention, and transfer of form for a
      multilimb closed sport skill. Two groups received either 100% relative frequency
      of KP or 33% relative frequency of KP while learning the soccer throw-in skill.
      Participants were boys between the ages of 11 and 14 years who were unfamiliar
      with the skill. Participants performed a 30-trial acquisition phase in which KP
      was provided about one of eight aspects of form. Following acquisition, five
      trial retention and transfer (to a target at a different distance than
      experienced in acquisition) tests were administered at 5 min, 24 hr, and 72 hr.
      Although no group differences were found for accuracy scores, the 33% group had
      higher form scores in acquisition and all retention and transfer tests. It was
      concluded that reducing the relative frequency of KP eliminated a dependency on
      KP to guide performance in acquisition, which was beneficial for maintaining form
      in conditions in which KP was absent.

PMID- 9777660
TI  - The development of self-perceptions of ability and achievement goals and their
      relations in physical education.
AB  - This study examined the development of self-perceptions of ability and
      achievement goals and their relationships in physical education. Three hundred
      and eight students in 4th, 8th, and 11th grades completed questionnaires
      assessing their goal orientations, conceptions of ability, and perceived
      competence in physical education. Analyses assessing grade-related changes in
      conceptions of ability and achievement goals showed that as the students
      progressed from grades 4 through 11, they were more likely to: (a) interpret
      ability as a stable capacity that may limit or increase the effect of effort on
      performance and (b) become ego-oriented. Analyses assessing relationships between
      variables of interest across grade level revealed that achievement goals were
      related to different conceptions of ability, students' self-ratings were
      significantly positively correlated to their teachers' ratings of their
      competence, and no consistent relationships emerged between achievement goals and
      perceived competence.

PMID- 9777661
TI  - Innovation in two alternative elementary school programs: why it works.
AB  - The purpose of this paper was to describe and interpret the factors that
      supported and maintained curricular innovation at two alternative elementary
      schools. The two schools have Project Adventure as their curriculum focus and use
      the concepts of risk, challenge, trust, cooperation, and problem solving;
      briefing and debriefing; and personal goal-setting contracts as part of their
      schoolwide curriculum (Project Adventure, 1991). Data were collected through
      formal interviews with the physical education teachers, the principals, and four
      classroom teachers at each school. Nonparticipant observation, field notes,
      informal interviews, and document analysis were also conducted. Inductive
      analysis and constant comparison were used to analyze and organize the data
      throughout the research process. Five factors emerged that supported the
      implementation of this innovative physical education program: a shared vision,
      external support for the schools' programs, curricula integration, centrality of
      physical education, and shared decision making. Project Adventure at these
      schools provides an example of substantive curricular reform where physical
      education was a critical element in the school programs.

PMID- 9777663
TI  - Students' perceptions of the physical education class environment for boys and
      girls and the perceived motivational climate.
AB  - Greek students (N = 310) responded to surveys concerning their perceptions of the
      physical education class environment. Based on factor and reliability analyses,
      14 scale scores were computed. Two depicted perceptions of teacher-initiated
      mastery orientation and teacher-initiated performance orientation. Six scale
      scores reflected the teacher's negative behavior toward boy's, focus on boys'
      learning, encouragement toward boys, autonomy given to boys, adjustment of the
      lesson for boys, and motivation of boys. Six identical scale scores were
      calculated assessing the physical education class climate for girls. The
      perception of a teacher who behaves differently toward boys and girls was
      negatively related to the perception of a teacher who tried to help all students
      to improve. It is suggested that a mastery orientation increases students'
      motivation and maintains equality in physical education.

PMID- 9777662
TI  - Practical knowledge in expert coaches: on-site study of coaching in sailing.
AB  - The purpose of this study was to analyze the practical knowledge of expert
      sailing coaches of the French team preparing for the 1996 Olympic Games in
      Atlanta. Coaching knowledge was studied from a cognitive ergonomics perspective
      based on the task activity model. According to this model, a task is a set of
      constraints facing individuals. To meet the demands imposed by these constraints,
      an individual engages in an adaptative activity which can be studied from the
      point of view of his or her knowledge and cognitive operating modes. In-depth
      interviews were conducted after observation of five training sessions, and the
      verbal protocols obtained were coded inductively. The results showed that
      coaching tasks were considered by coaches as a set of interacting constraints
      which generate complex, contradictory, and ill defined problems. Coaches'
      operating modes appeared to be based on organization routines, cognitive
      anticipation on flexible plans, flexible on-site adaptation, joint control of
      training with athletes, and involvement in the training situation based on past
      experiences.

PMID- 9777664
TI  - Confirmatory factor analysis of the Task and Ego Orientation in Sport
      Questionnaire with cross-validation.
AB  - Although a number of factor analytic studies have been conducted on the factorial
      validity of the Task and Ego Orientation in Sport Questionnaire (TEOSQ), the
      results have been equivocal. To further substantiate its evidence of validity,
      this study cross-validated the measurement model using a rigorous structural
      equation modeling (SEM) approach. Data collected from a college student sample
      were first analyzed on a calibration sample (n = 439). Results confirmed the two
      factor orthogonal structure representing the underlying task and ego
      orientations. The results were cross-validated on a validation sample (n = 439)
      using various SEM-based cross-validation procedures. Collectively, these findings
      support the construct validity of the TEOSQ as a measure of achievement goal
      orientation.

PMID- 9777665
TI  - Specificity of practice: the case of powerlifting.

PMID- 9777666
TI  - New frontiers in visual search: an exploratory study in live tennis situations.

PMID- 9777667
TI  - Prediction of VO2max before, during, and after 16 weeks of endurance training.

PMID- 9777668
TI  - Reliability of a protocol for testing endurance performance in runners and
      cyclists.

PMID- 9777669
TI  - Comments on "development of a cadence curl-up test for college students"
      (Sparling, Millard-Stafford, & Snow, 1997): concerns about validity and
      practicality.

PMID- 9777671
TI  - [Screening test by statistically reducing the number of the State-Trait Anxiety
      Inventory (STAI) items].
AB  - The purpose of the study is to find a method of mental examination which can be
      simply performed concurrently with physical examination during a regular check
      up. On a regular check-up, the state-trait anxiety inventor (STAI) was
      administered to 264 construction workmen engaged in reconstruction work for the
      Hanshin Awaji Great Earthquake. Data on a total of 40 STAI items, i.e., 20 state
      anxiety (A-State) items and 20 trait anxiety (A-Trait) items were subjected to
      multiple regression analysis and five items were extracted from A-State and five
      from A-Trait items as a practical tool for a simple screening test. The
      contribution rates of the respective five items for the total score were 90.0%
      for A-State and 88.5% for T-State. The correlation coefficients, r, between
      predicted and observed values were 0.949 (p < 0.01) for A-State and 0.940 (p <
      0.01) for A-Trait. Because of certain degrees of validity and reliability of each
      five-item system, it is considered that this method is useful as a simple
      screening test to roughly grasp the mental health of subjects and can be utilized
      for mental health care at offices.

PMID- 9777672
TI  - [A proposed method for evaluating short-term exposure condition].
AB  - High short-term exposure to toxic chemicals can occur during a workday, even if
      the daily average exposure is lower than the permissible exposure limit, because
      the exposure concentration varies from minute to minute. To protect workers from
      acute health effects due to high short-term exposure, the Japan Society for
      Occupational Health recommends that the maximum value for 15-min time-weighted
      average (15-min TWA) exposure during a workday should not exceed 1.5 times the
      occupational exposure limit for 8-hr TWA, and the American Conference of
      Governmental Industrial Hygienists issues the threshold limit value-short-term
      exposure limit (TLV-STEL), that is a 15-min TWA exposure which should not be
      exceeded at any time during a workday. A workday (8 hr) consists of thirty two 15
      min periods. If the thirty-two 15-min TWAs are measured, the short-term exposure
      situation can be appropriately evaluated by comparing the highest measured value
      with the standard value (e.g. TLV-STEL), but such continuous monitoring consumes
      a lot of cost and time. In this paper, we propose a method for evaluating short
      term exposure by using three or more measured values. This evaluation method
      corresponds to two different types of selection of sampling periods. One is a
      random selection of three or more 15-min periods among the 32 periods. If this
      selection is adopted, a comparison between the 98.44 percentile of the within-day
      distribution of 15-min TWAs and the standard value can be made by using one-sided
      tolerance factors, KI, KII and KIII, and the exposure situation is classified
      into four exposure classes at 95% and 50% confidence levels. Another is a random
      selection among high exposure periods. If this selection is adopted, a comparison
      between the specific percentile of the distribution and the standard value can be
      made with modified one-sided tolerance factors, and the exposure class is
      determined similarly. This method can provide a precise evaluation of exposure,
      so that it is useful in the industrial hygiene field.

PMID- 9777673
TI  - Brain injury in the premature infant: overview of clinical aspects,
      neuropathology, and pathogenesis.
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 two
      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
      neurology, neuropathology, and pathogenesis of these two lesions. Recent work
      suggests that the ultimate goal, prevention of the lesions, is potentially
      achievable. Periventricular hemorrhagic infarction may be preventable 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- 9777674
TI  - Intraventricular hemorrhage: emphasis on prevention.
AB  - Germinal matrix/intraventricular hemorrhage is a common type of cerebral injury
      in premature newborns. Based on the improved understanding of underlying
      pathogenetic mechanisms, numerous interventional strategies for prevention have
      been proposed. This article summarizes and evaluates the efficacy and safety of
      major interventions that are currently under consideration for the prevention of
      germinal matrix/intraventricular hemorrhage.

PMID- 9777675
TI  - Posthemorrhagic hydrocephalus and brain injury in the preterm infant: dilemmas in
      diagnosis and management.
AB  - Advances in neonatal critical care have reduced the incidence of intraventricular
      hemorrhage (IVH) in the newborn. Paradoxically, however, the prevalence of the
      complications of IVH including posthemorrhagic hydrocephalus (PHHC) has
      increased. By virtue of its association with long-term neurodevelopmental
      disability, posthemorrhagic hydrocephalus is an ominous diagnosis in the
      premature infant. Animal models have demonstrated that ventricular distention may
      cause direct cerebral parenchymal injury. Evidence for secondary parenchymal
      injury in the premature infant with PHHC is by necessity indirect. The precise
      impact of secondary parenchymal injury on the overall neurological outcome of
      premature infants with PHHC remains unclear in large part because of the
      vulnerability of the immature brain to other forms of injury (e.g.,
      periventricular leukomalacia) that may be difficult to distinguish from injury
      due to distention. Furthermore, parenchymal injury due to PVL may cause
      ventricular enlargement that does not benefit from CSF diversion. Because these
      primary and secondary mechanisms of injury may operate concurrently, the precise
      or dominant cause of ventricular enlargement is often difficult to establish with
      certainty in the neonatal period. These diagnostic dilemmas have in turn impeded
      the development and evaluation of therapies specifically aimed at reversing
      ventricular distention and preventing secondary parenchymal injury. This article
      focuses on the current dilemmas in diagnosis and management of this potentially
      reversible form of injury as well as on potential future strategies for its
      prevention.

PMID- 9777676
TI  - Human oligodendroglial development: relationship to periventricular leukomalacia.
AB  - Periventricular leukomalacia in the premature infant is a lesion of cerebral
      white matter with its greatest period of risk when white matter is immature, that
      is, when oligodendrocyte precursors are proliferating and differentiating, and
      before myelin sheaths are actively synthesized. Although the pathogenesis of
      perinatal cerebral white matter damage involves multiple factors, the correlation
      of the timing of the lesion with dominance of oligodendrocyte precursors in
      cerebral white matter suggests that intrinsic factors related to oligodendrocyte
      precursors are critical. Ischemia and infection have both been implicated as
      causes of perinatal white matter damage. Major mechanisms underlying
      oligodendrocyte injury in ischemia include glutamate toxicity, free-radical
      injury, and cytokine damage mediated by macrophages accompanying ischemia-induced
      inflammation. Factors related to a vulnerability of immature oligodendrocytes to
      ischemia potentially include a developmental lack of antioxidant enzymes to
      mediate oxidative stress. Cytokine-mediated injury to oligodendrocytes is also
      potentially important. A complete understanding of the role of immature white
      matter in the pathogenesis of periventricular leukomalacia is essential for
      developing strategies to prevent it.

PMID- 9777677
TI  - Infection remote from the brain, neonatal white matter damage, and cerebral palsy
      in the preterm infant.
AB  - This review synthesizes the literature supporting the hypothesis that infection
      during or even before pregnancy remote from the fetal brain leads to neonatal
      white matter damage (NWMD) and its long-term sequelae, including cerebral palsy.
      First, a framework of five dimensions is presented, including the spectrum of
      NWMD, its relationship with gestational age, its clinical spectrum, the
      expressions and correlates of infection, and the mother/child dyad. Second, a
      summary of the plethora of support for the remote infection/NWMD-hypothesis is
      presented by drawing on studies published over the past three decades. Although
      an epidemiological perspective is prominent, we invoke molecular explanations
      (especially the cytokine hypothesis) for observed associations. Third, the
      article concludes with a section on future studies needed to characterize and
      eliminate (pre-) pregnancy infections in the mother and to identify and evaluate
      potentially neuroprotective strategies in the fetus.

PMID- 9777678
TI  - Antenatal glucocorticoid, magnesium exposure, and the prevention of brain injury
      of prematurity.
AB  - Prevention of perinatal white matter injury with or without severe
      intraventricular hemorrhage (IVH) is critical to reduce cerebral palsy (CP) in
      premature infants. Antenatal therapies that may afford neuroprotection include
      glucocorticoids, which are associated with a significant reduction in severe IVH,
      and magnesium, which is associated with reduced CP. Potential protective
      mechanisms of glucocorticoids include a direct effect on brain, improved
      respiratory function, and more stable blood pressure hemodynamics. Because
      magnesium is often administered to mothers with pregnancy-induced hypertension, a
      condition associated with reduction in severe IVH, the independent
      neuroprotective role of magnesium remains unclear and warrants additional
      studies.

PMID- 9777679
TI  - Remyelination: cellular and gene therapy.
AB  - Dysfunctional myelination or oligodendroglial abnormalities play a prominent role
      in a vast array of pediatric neurological diseases of genetic, inflammatory,
      immunological, traumatic, ischemic, developmental, metabolic, and infectious
      causes. Recent advances in glial cell biology have suggested that effective
      remyelination strategies may, indeed, be feasible. Evidence for myelin repair is
      accumulating in various experimental models of dysmyelinating and demyelinating
      disease. Attempts at remyelination have either been directed towards creating
      myelin de novo from exogenous sources of myelin-elaborating cells or promoting an
      intrinsic spontaneous remyelinating process. Ultimately, some disorders of myelin
      may require multiple repair strategies, not only the replacement of dysfunctional
      cells (oligodendroglia) but also the delivery or supplementation of gene products
      (i.e., growth factors, immune modulators, metabolic enzymes). Although primary
      oligodendrocytes or oligodendroglial precursors may be effective for glial cell
      replacement in certain discrete regions and circumstances and although various
      genetic vectors may be effective for the delivery of therapeutic molecules,
      multipotent neural stem cells may be most ideally suited for both gene transfer
      and cell replacement on transplantation into multiple regions of the central
      nervous system under a wide range of pathological conditions. We propose that, by
      virtue of their inherent biological properties, neural stem cells possess the
      multifaceted therapeutic capabilities that many diseases characterized by myelin
      dysfunction in the pediatric population may demand.

PMID- 9777681
TI  - Strength training. Single versus multiple sets.
AB  - Perhaps the most controversial element of any strength training programme is the
      number of sets required to increase muscular strength and hypertrophy. There is a
      prevalent belief that at least 3 sets of each exercise are required to elicit
      optimal increases in strength and hypertrophy. However, most of the studies that
      reported the results of training with single versus multiple sets do not
      substantiate this tenet. In fact, the preponderance of evidence suggests that for
      training durations of 4 to 25 weeks there is no significant difference in the
      increase in strength or hypertrophy as a result of training with single versus
      multiple sets. Because of the design limitations of these studies, conclusions
      concerning the efficacy of multiple sets should be tentative. However, there is
      little scientific evidence, and no theoretical physiological basis, to suggest
      that a greater volume of exercise elicits greater increases in strength or
      hypertrophy. This information may represent an important practical application of
      time-efficient, low-volume exercise.

PMID- 9777680
TI  - The female athlete. The triad of disordered eating, amenorrhoea and osteoporosis.
AB  - Over the last few decades, the number of women participating in organised sports
      has grown dramatically. Participation in sports has led to significant health
      benefits for these women; however, several medical disorders have become more
      prevalent as the number of female athletes has increased. In response to the
      increase in the number of female athletes and potential medical disorders, the
      American College of Sports Medicine coined the term 'the female athlete triad' in
      1992. The female athlete triad is a serious syndrome comprising 3 interrelated
      components: (i) disordered eating; (ii) amenorrhoea; and (iii) osteoporosis. The
      female athlete triad is a syndrome that can be prevented. Medical management of
      the female athlete triad requires a multidisciplinary approach, with early
      diagnosis and treatment being key factors. More studies are required to determine
      its causes, prevalence and consequences and to develop an optimal treatment
      strategy. All individuals, including coaches and parents, who are working with
      physically active girls and women should be educated about these disorders, and
      they should develop strategies to prevent, recognise and treat the female athlete
      triad.

PMID- 9777682
TI  - Autonomic regulation of the circulation during exercise and heat exposure.
      Inferences from heart rate variability.
AB  - Minimal information is available on the autonomic response to exercise under
      adverse environmental conditions. Traditionally, pharmacological blockade has
      been used to study autonomic responsiveness but, owing to its invasive nature,
      such studies have been limited in their scope. Recent advances in
      electrocardiographic tape recording, telemetry and associated computing systems
      have provided investigators with noninvasive methods for assessing the autonomic
      response to various physiological stressors. This article describes methods for
      the analysis of heart rate variability (HRV) and discusses the reports of those
      who have used HRV analysis to evaluate autonomic regulation during exercise, heat
      exposure and the combination of these 2 stressors. Spectral analysis of HRV
      reduces variations in the R-R interval into component sine waves of differing
      amplitude and frequency. Amplitude (variance) is displayed as a function of
      frequency, and power (cumulative variance) is calculated for specified frequency
      ranges (< 0.03 Hz, 0.03 to 0.15 Hz and 0.15 to 0.5 Hz). Parasympathetic nervous
      system activity can be inferred from the several indices of high frequency power;
      however, the estimation of sympathetic nervous system activity from low frequency
      power is more problematic. Data on HRV have shown that sympathovagal regulation
      during exercise is dependent on the intensity of the activity and the
      environmental conditions. At the onset of exercise, heart rate is increased by a
      reduction in vagal tone and a temporary increase in sympathetic tone. A
      continuation of physical activity is associated with a continued withdrawal of
      vagal activity and an attenuation of sympathetic nervous system tone. However,
      with the additional stimulus of a heated environment, sympathetic activity
      remains increased throughout exercise.

PMID- 9777685
TI  - A Bayesian hierarchical survival model for the institutional effects in a multi
      centre cancer clinical trial.
AB  - In randomized clinical trials comparing treatment effects on diseases such as
      cancer, a multi-centre trial is usually conducted to accrue the required number
      of patients in a reasonable period of time. While we interpret the average
      treatment effect, it is necessary to examine the homogeneity of the observed
      treatment effects across institutions, that is, treatment-by-institution
      interaction. If the homogeneity is confirmed, the conclusions concerning
      treatment effects can be generalized to a broader patient population. In this
      paper, a Bayesian hierarchical survival model is used to investigate the
      institutional effects on the efficacy of treatment as well as on the baseline
      risk. The marginal posterior distributions are estimated by a Markov chain Monte
      Carlo method, that is, Gibbs sampling, to overcome current computational
      limitations. The robustness of the inferences to the distributional assumption
      for the random effects is also examined. We illustrate the methods with analyses
      of data from a multi-centre cancer clinical trial, which investigated the
      efficacy of immunochemotherapy as an adjuvant treatment after curative resection
      of gastric cancer. In this trial there is little difference in the treatment
      effects across institutions and the treatment is shown to be effective, while
      there appears to be substantial variation in the baseline risk across
      institutions. This result indicates that the observed treatment effects might be
      generalized to a broader patient population.

PMID- 9777684
TI  - Common sports injuries in young tennis players.
AB  - Tennis is a popular racquet sport played by boys, girls, men and women. Tennis
      players frequently begin playing in childhood and may continue playing into late
      adulthood. Preadolescent and adolescent players have open growth plates and a
      reduced muscle power, lower level of coordination and smaller stature compared
      with adult players. The physical characteristics of the young tennis player mean
      that unique demands are placed on the developing athlete which can, in turn, be
      associated with different types and patterns of injury. The most common types of
      injury in tennis players of all ages are muscle sprains and ligament sprains
      secondary to overuse. These are a particular problem in the adolescent age group
      because, in general, this group begin playing with a lower level of physical
      conditioning. Fortunately, injuries in younger players are usually not
      longstanding and the overuse (chronic) problems seen in older players, such as
      patellar tendinosis and tennis elbow, are less common in younger players.
      Anatomically, lower extremity injuries are twice as common as those to the upper
      extremity or spine, with ankle injury being the most common. Prevention of injury
      in young tennis players, or at least a reduction in the incidence, is possible.
      Some traumatic injuries, including contusions, abrasions, lacerations and
      fractures, may be unavoidable as a result of aggressive play, but others may be
      prevented by monitoring equipment and the court surface to ensure a safe field of
      play. The prime target of prevention in young tennis players should be overuse
      injuries. The principles of 'overload' and staged involvement are of particular
      importance in this age group. A gradual, progressive increase in the intensity of
      tennis practice, the slow introduction of new court surfaces and a staged
      progression in the teaching of tennis skills can help to reduce the incidence of
      injury in young tennis players.

PMID- 9777687
TI  - An empirical study of the effect of the control rate as a predictor of treatment
      efficacy in meta-analysis of clinical trials.
AB  - If the control rate (CR) in a clinical trial represents the incidence or the
      baseline severity of illness in the study population, the size of treatment
      effects may tend to very with the size of control rates. To investigate this
      hypothesis, we examined 115 meta-analyses covering a wide range of medical
      applications for evidence of a linear relationship between the CR and three
      treatment effect (TE) measures: the risk difference (RD); the log relative risk
      (RR), and the log odds ratio (OR). We used a hierarchical model that estimates
      the true regression while accounting for the random error in the measurement of
      and the functional dependence between the observed TE and the CR. Using a two
      standard error rule of significance, we found the control rate was about two
      times more likely to be significantly related to the RD (31 per cent) than to the
      RR (13 per cent) or the OR (14 per cent). Correlations between TE and CR were
      more likely when the meta-analysis included 10 or more trials and if patient
      follow-up was less than six months and homogeneous. Use of weighted linear
      regression (WLR) of the observed TE on the observed CR instead of the
      hierarchical model underestimated standard errors and overestimated the number of
      significant results by a factor of two. The significant correlation between the
      CR and the TE suggests that, rather than merely pooling the TE into a single
      summary estimate, investigators should search for the causes of heterogeneity
      related to patient characteristics and treatment protocols to determine when
      treatment is most beneficial and that they should plan to study this
      heterogeneity in clinical trials.

PMID- 9777688
TI  - The application of sample selection models to outcomes research: the case of
      evaluating the effects of antidepressant therapy on resource utilization.
AB  - Non-randomized studies of treatment effects have come under criticism because of
      their failure to control for potential biases introduced by unobserved variables
      correlated with treatment selection and outcomes. This paper describes the basic
      concepts of sample selection models--a technique used widely in the economics
      evaluation literature for nearly two decades--and discusses the potential role of
      these models in outcomes research. In addition, it presents a case study of the
      application of the sample selection modelling approach to evaluation of the
      effects of antidepressant therapies on medical expenditures for physician
      services. This case study presents empirical comparisons of alternative model
      specifications and discusses practical issues in evaluation of sample selection
      models. We demonstrate that, in this particular case, sample selection models
      yield very different conclusions regarding treatment effects than traditional
      ordinary least squares regression.

PMID- 9777686
TI  - Regression with bounded outcome score: evaluation of power by bootstrap and
      simulation in a chronic myelogenous leukaemia clinical trial.
AB  - Evaluation of the treatment effect on cytogenetic ordered categorical response is
      considered in patients treated for chronic myelogenous leukaemia (CML) in a
      clinical trial initiated by the East German Group for Hematology and Oncology. A
      simulation model for the cytogenetic response (per cent of Philadelphia
      chromosome positive metaphases) serially measured in CML patients was constructed
      to describe roughly the sparse information available in medical literature. The
      model was used to construct a summary measure of response and to formulate the
      treatment effect as a regression with U-shape distributed ordered categorical
      data. Two simple models (vertical shift model and pooled conditional response
      model) were specifically designed to model the treatment effect 'observed' in a
      simulated 'pilot' data set. The powers were contrasted with the traditional
      proportional odds and binary models. The comparison was based both on repeated
      sampling from the simulated model and on bootstrap of 'given' pilot data set. We
      show that the specific models that address the treatment effect directly (as
      anticipated from pilot data) can gain in power as compared to the traditional
      proportional odds model when evaluated by bootstrap. However, the proportional
      odds model appears to be better with repeated sampling from the simulation model.
      To explain this discrepancy we generated 'pilot data sets' repeatedly from the
      simulation model and showed that the ordering of the bootstrap power estimates is
      unstable with reasonably complex models dependent on the random fall of the pilot
      data sets. This phenomenon clearly limits the usefulness of subtle modelling the
      form of the treatment difference observed in a small pilot data set.

PMID- 9777683
TI  - The influence of exercise-induced plasma volume changes on the interpretation of
      biochemical parameters used for monitoring exercise, training and sport.
AB  - A number of studies have demonstrated considerable plasma volume changes during
      and after exposure to different environmental and physiological conditions. These
      changes are thought to result from transient fluid shifts into (haemodilution)
      and out of (haemoconcentration) the intravascular space. If the levels of plasma
      constituents are to be routinely measured for research purposes or used as
      indicators of training adaptation or the health of an athlete, then it is
      important to consider the dynamic nature of plasma volume. Controversy still
      exists over the relevance of plasma volume interactions with plasma constituent
      levels, and while some investigators have taken plasma volume shifts into
      account, others have chosen to ignore these changes. Bouts of acute exercise have
      been shown to produce a transient haemoconcentration immediately after long
      distance running, bicycle ergometry and both maximal and submaximal swimming
      exercise. While these changes are transient, lasting only a few hours, other
      studies have reported a longer term haemodilution following acute exercise. In
      addition, endurance training has been shown to cause long term expansion of the
      plasma volume. It would, therefore, seem important to consider the influence of
      plasma volume changes on plasma solutes routinely measured for research, and as
      markers of training adaptation, prior to arriving at conclusions and
      recommendations based purely on their measured plasma level. To further confound
      this issue, plasma volume changes are known to be associated with heat
      acclimatisation, hydration state, physical training and postural changes, all of
      which may differ from one experiment or exercise bout to the next, and should
      thus be taken into account.

PMID- 9777689
TI  - Covariate measurement error and the estimation of random effect parameters in a
      mixed model for longitudinal data.
AB  - We explore the effects of measurement error in a time-varying covariate for a
      mixed model applied to a longitudinal study of plasma levels and dietary intake
      of beta-carotene. We derive a simple expression for the bias of large sample
      estimates of the variance of random effects in a longitudinal model for plasma
      levels when dietary intake is treated as a time-varying covariate subject to
      measurement error. In general, estimates for these variances made without
      consideration of measurement error are biased positively, unlike estimates for
      the slope coefficients which tend to be 'attenuated'. If we can assume that the
      residuals from a longitudinal fit for the time-varying covariate behave like
      measurement errors, we can estimate the original parameters without the need for
      additional validation or reliability studies. We propose a method to test this
      assumption and show that the assumption is reasonable for the example data. We
      then use a likelihood-based method of estimation that involves a simple extension
      of existing methods for fitting mixed models. Simulations illustrate the
      properties estimators.

PMID- 9777690
TI  - Modelling age-specific risk: application to dementia.
AB  - We give up-to-date methods for estimating the age-specific incidence of a disease
      and for estimating the effect of risk factors. We recommend taking age as the
      basic time scale of the analysis; then, the hazard function can be interpreted as
      the age-specific incidence of the disease. This choice raises a delayed entry
      problem. We present three methods: the person-years method; the smoothed Nelson
      Aalen estimator, and the penalized likelihood approach. When explanatory
      variables are available, the Poisson model and the Cox model with delayed entry
      may be used for estimating relative risks; the penalized likelihood approach can
      also be used. We apply these methods to estimate the age-specific incidence of
      dementia using data from a large cohort study, Paquid. This 5-year study followed
      a random initial sample of 3675 subjects with 190 incident cases of dementia. We
      compare the estimates based on the three possible methods. The estimated
      incidences computed separately for men and women cross and it is verified that a
      non-proportional hazards model for gender holds; women below 75 have a lower risk
      than men while women above 75 have a higher risk.

PMID- 9777691
TI  - Incorporating correlations between measurements into the estimation of age
      related reference ranges.
AB  - An LMS-based maximum likelihood method of fitting age-related reference ranges is
      extended to incorporate non-independent measurements by including the matrix of
      the correlations between standard normalized repeat measurements into the
      likelihood. The likelihood is maximized via iterative re-estimation of the
      correlation structure and the reference range parameters until convergence is
      achieved. The correlation structure is explicitly modelled and the extent to
      which the estimated centiles depend on the adequacy with which the correlation
      structure is modelled is investigated. The method is illustrated using CD4 counts
      of uninfected children born to HIV-1 infected women. This data set consists of
      5063 CD4 counts taken from 745 children at irregular ages between birth and 10
      years of age. The data exhibited a strong correlation structure with correlations
      decreasing with increasing time between measurements and being lower for younger
      measurement ages. However, incorporation of the correlation had little effect on
      the choice of model for the median or on the fitted centiles or their precision.

PMID- 9777692
TI  - A simulation study comparing tests for the equality of coefficients of variation.
AB  - The coefficient of variation is commonly used in medical and biological sciences.
      In this paper, several parametric and non-parametric tests for the equality of
      coefficients of variation in kappa populations are reviewed. Simulation studies
      are conducted to compare the sizes and power of these tests. It is found that the
      parametric tests perform well if the data are normally distributed, but perform
      poorly if otherwise. The non-parametric test, however, is rather robust against
      the underlying distribution. An example using data of the Quality Assurance
      Program from the Hong Kong Medical Technology Association in Haematology and
      Serology is provided. The insensitivity of the non-parametric test to outliers is
      demonstrated.

PMID- 9777693
TI  - Confidence intervals for differences in correlated binary proportions.

PMID- 9777694
TI  - Immunosuppression in pancreas transplantation: progress, problems and
      perspective.
AB  - Through 1997, over 10,000 pancreas transplants have been performed world-wide,
      with 88% being simultaneous kidney-pancreas transplants (SKPTs). Current 1-year
      patient survival exceeds 90% and pancreas graft survival (complete insulin
      independence) exceeds 80% for SKPT, 70% for sequential pancreas after kidney
      transplant (PAKT), and 65% for pancreas transplant alone (PTA). According to
      Registry data, rejection accounts for 32% of graft failures in the first year
      after pancreas transplantation. However, improving outcomes are expected to
      continue with the evolution of treatment protocols. Most pancreas transplant
      centres employ quadruple drug immunosuppression with anti-lymphocyte induction,
      using either a monoclonal or polyclonal antibody agent. In recent years, there
      has been an overall decline in the use of antibody-induction therapy from 90%
      during 1987-93, to 83% of pancreas transplants performed during 1994-97.
      Maintenance immunosuppression is triple therapy consisting of a calcineurin
      inhibitor (cyclosporine or tacrolimus), corticosteroids, and an anti-metabolite
      such as azathioprine (AZA) or mycophenolate mofetil (MMF). Prior to 1995, nearly
      all pancreas transplant recipients were managed with Sandimmune. Since 1986,
      tacrolimus-based therapy has been used in approximately 20% of cases, and a new
      microemulsion formulation of cyclosporine (Neoral) has replaced Sandimmune in
      contemporary post-transplant immunosuppression. In addition, MMF is replacing AZA
      as part of the standard immunosuppressive regimen following pancreas
      transplantation. At present, a number of centres are conducting various trials
      with new drug combinations including either Neoral or tacrolimus in combination
      with steroids and MMF, with or without antibody-induction therapy. From 1994 to
      1997, the 1-year rates of immunologic graft loss have decreased to 2% after SKPT,
      9% after PAKT, and 16% after PTA. The current array of new immunosuppressive
      agents are providing more effective control of rejection and permitting solitary
      pancreas transplantation to become an accepted treatment option in diabetic
      patients without advanced complications. The apparent potency of new drug
      combinations has also resulted in a resurgence of interest in steroid withdrawal.
      Immunosuppressive strategies will continue to evolve to achieve effective control
      of rejection while minimizing injury to the allograft and risk to the patient. In
      addition, new regimens must not only address the issue of specific drug
      toxicities, but also long-term economic, metabolic, and quality of life outcomes.
      Pancreas transplantation will remain an important alternative in the treatment of
      diabetic patients until other strategies are developed that can provide equal
      glycaemic control with less immunosuppression and overall morbidity.

PMID- 9777695
TI  - All or none peripheral tolerance induction in H-Y antigen-specific TCR transgenic
      mice.
AB  - In in vivo tolerance induction, the dose of tolerogen injected is generally
      linearly correlated to the length of tolerance induced. Small, medium and large
      doses are related to no, partial and long-term tolerance, respectively. However,
      even with injection of substantially large doses of tolerogen, the length of
      tolerance induced varies over a wide range. Most of the recipients can still
      reject donor grafts. In this study, it is shown that the linear dose-response can
      be altered into an all or nothing response in a H-Y antigen-specific TCR
      transgenic (Tg) mouse model. In thymectomized female Tg mice, injection of 3, 30
      and 100 x 10(6) male spleen cells was correlated to no, partial and massive
      deletion of Tg (alpha T beta T) CD8 cells, respectively. When the thymectomized
      Tg mice were injected with 9 x 10(6) T cell-enriched (T+) male cells, one half of
      the recipients showed no deletion of alpha T beta T cells, and in the other half
      massive deletion occurred. In complete correlation with deletion, all male skin
      grafts were rejected in the undeleted group as PBS-injected controls, whereas
      with massive deletion they were indefinitely tolerized. Thus, partial deletion
      and partial tolerance can be avoided. Injection of 18 x 10(6) male T+ cells
      induced long-term tolerance in all the recipients. The all or none T cell
      deletion and long-term tolerance induction has not only significant implications
      in understanding the mechanism of peripheral tolerance induction, but also in
      tolerance induction in transplantation, gene therapy and the prevention and
      treatment of autoimmune diseases.

PMID- 9777696
TI  - Stress protein-induced immunosuppression: inhibition of cellular immune effector
      functions following overexpression of haem oxygenase (HSP 32).
AB  - This is the first report on suppression of immune effector functions following
      upregulation of heat shock protein 32 (HSP 32), known as haem oxygenase (HO-1).
      Here we evaluated the effect of cobalt-protoporphyrin (CoPP)-induced HO-1
      expression on cell-mediated immune responses. Administration of CoPP to CBA mice
      resulted in overexpression of HO-1 in the spleen, liver and kidneys. In vitro
      measurements of T cell-mediated and NK-cell-mediated cytotoxicity in spleens from
      CoPP-treated animals demonstrated a severe suppression of their effector
      functions while administration of Zn-PP or vitamin B12 had no effect.
      Furthermore, CoPP therapy decreased the lymphoproliferative alloresponse and
      differentiation of cytotoxic T cells. Inhibition of proliferation appeared to be
      due to cell growth arrest with an increased number of cells staying in G0/G1
      phase. Despite the suppressed proliferative response, IL-2 production in the MLR
      was not inhibited. In contrast, CoPP decreased the production of IL-10, IFN-gamma
      and TNF-alpha. In vivo, CoPP prolonged the survival of heterotopic heart
      allografts in mice. The immunosuppressive effects following CoPP-mediated
      upregulation of HO-1 were similar to those observed after peptide-mediated
      upregulation of HO-1. The results indicate that overexpression of HO results in
      the inhibition of several immune effector functions and thus provides an
      explanation for stress-induced immunosuppression.

PMID- 9777697
TI  - Malononitrilamides 715 and 279 prevent accelerated cardiac allograft rejection
      synergistically with cyclosporin A in presensitized rats.
AB  - A77 1726 is a malononitrilarnide (MNA) and the active metabolite of leflunomide.
      Leflunomide has been extensively investigated and shown to be a potent
      immunosuppressive drug. However, the half-life of A77 1726 is about 15-18 days in
      humans and the leflunomide is, therefore, currently being evaluated for the
      treatment of autoimmune disease and not for transplantation. The search for
      analogues has led to the development of MNA 715 and 279, derivatives of A77 1726.
      Previous limited experimental experience has shown these MNAs to prevent skin
      allograft and xenograft rejection and graft-versus-host disease in rodents, and
      to reverse ongoing allograft rejection. The aim of the present study was to
      verify the efficacy of these MNAs in a cardiac retransplant model of sensitized
      rats, concerning prevention of accelerated rejection, inhibition of antibody
      production and interaction with cyclosporin A (CsA). Heterotopic cardiac
      transplantation and retransplantation in Dark Agouti (DA) to Piebald Virol Glaxo
      (PVG) rats was used. Subgroups of rats were given either CsA, MNA 715, MNA 279 or
      combined CsA/MNA for 10 days starting either day 0 or day -1, as of regrafting or
      no treatment. Titres of allospecific IgM and IgG were quantitated by flow
      cytometry. Ten days of MNA 715 or 279 from day -1 prevented accelerated rejection
      of the retransplant, as did CsA. Neither treatment given from day 0 prevented
      rejection within 24 h. However, a combination of MNA 715 or 279 and CsA from day
      0 effectively prevented accelerated regraft rejection. Production of specific
      alloantibodies was reduced in all immunosuppressed subgroups, IgG titres at day 7
      in MNA-treated subgroups being significantly lower compared with those in the CsA
      treated subgroup. In conclusion, MNA 715 and 279 were shown to be potent
      immunosuppressants with the capacity to prevent accelerated regraft rejection in
      rat cardiac transplants, most efficiently in combination with CsA, and to
      suppress specific alloantibody production.

PMID- 9777698
TI  - An association between antibodies specific for endothelial cells and renal
      transplant failure.
AB  - Human leucocyte antigen (HLA)-specific antibodies, present at the time of
      transplant, cause renal transplant rejection but cases of rejection of HLA
      identical renal transplants indicate that antibodies to non-HLA antigens may also
      be detrimental. There is increasing evidence that antibodies to antigens present
      on endothelial cells and monocytes, and on endothelial cells alone, are
      associated with transplant rejection. We investigated 105 patients with failed
      renal transplants for the presence of endothelial cell reactive antibodies and
      compared them with 94 successful transplant patients to determine the role of non
      HLA antibodies in transplant failure. Patient sera were tested by enzyme-linked
      immunoabsorbent assay (ELISA) using as a target fixed cells either from the
      endothelial/epithelial cell line EAHy.926 or primary cultures of human umbilical
      vein endothelial cells. Antibody binding was detected using an alkaline
      phosphatase-conjugated anti-human immunoglobulin G (IgG) antibody. Fourteen of
      the 105 failed transplant patients had endothelial cell-reactive antibodies as
      compared with only three of the 94 patients with successful transplants (Fisher's
      exact test, p = 0.02). Antibody-positive sera were absorbed with the epithelial
      cell line A549 to remove antibodies directed against the epithelial component of
      EAHy.926 and with a pool of lymphoblastoid cell line cells to remove HLA-specific
      antibodies. Absorption did not reduce antibody activity showing the antibodies to
      be directed against endothelial cell determinants. Antibody-positive sera were
      also tested by flow cytometry against the monocyte cell line THP-1 and 13 of the
      14 patients were negative. In conclusion, we have demonstrated the presence of
      IgG antibodies directed against endothelial cell determinants in renal transplant
      recipients in association with renal transplant failure.

PMID- 9777699
TI  - Prevention of hyperacute rejection by phosphatidylinositol-anchored mini
      complement receptor type 1.
AB  - Complement receptor type 1 (CR1, CD35) contains both factor I cofactor activity
      and convertase decay accelerating activity, but is, in general, thought to be an
      extrinsic regulator of complement activation. In this study, we prepared a
      phosphatidylinositol (PI)-anchored mini-CR1, which is composed of the short
      consensus repeat (SCR) 8-11 of CR1 and the PI anchor of DAF, and expressed it
      stably on a swine endothelial cell (SEC) line. We then examined the intrinsic
      regulatory activity of the mini-CR1, with respect to complement-mediated cell
      lysis as an in vitro hyperacute rejection model of a swine to human discordant
      xenograft. Flowcytometric profiles of the stable SEC lines with mini-CR1 showed a
      moderate level of expression for this molecule. Mini-CR1 blocked human complement
      mediated cell lysis by approximately 50-70% on SEC. From the data of this study
      and our previous studies, mini-CR1 was more effective than membrane cofactor
      protein (MCP, CD46), and as effective as decay accelerating factor (DAF, CD55) in
      this system. The results suggest that PI-anchored mini-CR1 represents a useful
      molecule for clinical xenotransplantation.

PMID- 9777700
TI  - Methotrexate regulates ICAM-1 expression in recipients of rat cardiac allografts.
AB  - The means by which methotrexate (MTX) mediates immunosuppression at low doses
      remains to be elucidated. MTX has been shown to inhibit the adherence of
      neutrophils and fibroblasts to endothelial cells in vitro. The hypothesis that
      MTX treatment may affect cellular adherence by downregulating cell adhesion
      molecule expression formed the rationale for these studies. Previous studies of
      rat cardiac transplant recipients in our laboratory demonstrated that low-dose
      MTX treatment alone significantly inhibits the expression of the leucocyte beta 2
      integrin subunit, CD18. These investigations have addressed whether low-dose MTX
      treatment might also affect the expression of the beta-integrin counter-receptor,
      ICAM-1, a cell adhesion molecule which may be induced on endothelial cells during
      an immune response. The degree to which low-dose cyclosporine A and low-dose MTX
      treatment alone, and in combination, impact cell adhesion molecule expression has
      been studied in Brown Norway (BN) to Lewis (Lew) rat accessory cervical heart
      allografts. According to both Northern blot and immunohistochemical analysis,
      ICAM-1 expression was upregulated in graft regional lymph nodes and in the spleen
      of untreated cardiac allograft recipients within 6 h post-transplantation.
      Despite induction of VCAM-1 expression, ICAM-1 expression remained low or
      undetectable in cardiac allograft tissue as measured both by reverse
      transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemical
      analysis. These data suggest that ICAM-1 may function in leucocyte trafficking
      through lymphoid organs, such as the lymph nodes and spleen, but not directly in
      graft leucocyte recruitment during BN to Lew rat cardiac allograft rejection.
      Despite prolonged allograft survival with cyclosporine A alone and combination
      cyclosporine A/MTX, these treatments did not result in diminished steady-state
      ICAM-1 mRNA levels in regional lymph nodes or spleen of cardiac allograft
      recipients. MTX treatment alone, however, substantially diminished ICAM-1
      expression in allograft recipient lymphoid tissues. These studies demonstrate for
      the first time in vivo using a rat model of acute allograft rejection that MTX
      but not cyclosporine treatment downregulates cell adhesion molecule expression.
      Low-dose MTX treatment alone, however, is not sufficient to result in prolonged
      BN to Lew rat cardiac allograft survival. The means by which combination low-dose
      cyclosporine A and MTX treatment results in prolonged rat cardiac allograft
      survival over low-dose cyclosporine treatment alone remain(s) to be clarified.

PMID- 9777701
TI  - Effects of cyclosporine A and methotrexate on CD18 expression in recipients of
      rat cardiac allografts.
AB  - Recent advances in the study of the molecular basis of inflammation suggest that
      cell-cell interactions mediated by specific adhesion molecules could be new
      targets for immunosuppression. Methotrexate (MTX)-treated cells in vitro have
      demonstrated decreased neutrophil-endothelial cell adhesion associated with
      increased release of adenosine from endothelial cells, while the direct role of
      cyclosporine A (CSA) in the regulation of cell adhesion molecule (CAM) expression
      is less well-defined. Since the adhesion of leucocytes to endothelial cells via
      CAMs is necessary for leucocyte extravasation and infiltration into graft tissue
      during allograft rejection, these studies have addressed the hypothesis that MTX
      treatment of cardiac transplant recipients may affect cellular adherence by
      downregulating cell adhesion molecule expression. Using a vascularized method of
      rat cardiac transplantation, our studies have previously demonstrated that low
      doses of the immunosuppressive agents CSA and MTX, when used in combination,
      significantly increase allograft survival. According to reverse transcriptase
      polymerase chain reaction (RT-PCR) methodology to measure changes in steady-state
      CD18 mRNA levels, and immunohistochemistry to assess transplant CD18 protein
      levels in situ, both CD18 transcript and protein levels were significantly
      increased in untreated allografts when compared to isograft tissues on days 3
      through to 7 post-transplant. Whereas, both low-dose CSA alone and low-dose MTX
      alone treatment resulted in similar levels of graft leucocyte infiltration, MTX
      treated recipients demonstrated lower levels of CD18 expression when compared to
      low-dose CSA alone treatment. The results of immunohistochemical staining for T
      cells, where significantly fewer T cells were observed in rat cardiac allografts
      after low-dose MTX treatment alone compared to low-dose CSA treatment, were
      noteworthy. Results of these studies indicate that CD18 expression and
      infiltrating T cell numbers in Brown Norway (BN) to Lewis (Lew) rat cardiac
      allografts are significantly diminished with low-dose MTX treatment. The
      immunosuppressive effects of MTX, therefore, may be related to its ability to
      interfere with an early step during the cell-mediated immune response, namely the
      firm binding or 'adhesion' of leucocytes to the endothelium during
      transendothelial migration.

PMID- 9777702
TI  - Low temperature photolysis of denatured nitrosyl hemoproteins.
AB  - Photolysis of denatured HbNO were carried out at temperatures below 26 K. The
      normalized kinetic curves were fitted using either two exponentials or a
      conformational substate energy distribution or a fractal model. The parameters
      are related to the protein structure. The two exponentials model assumes the
      existence of two fractions of photolysed molecules that rebind with slow and fast
      reaction rates. Only the slow reaction rate is sensitive to the denaturation
      process. The pre-exponential factor and the peak energy of the substate
      distribution values suggest an increase in the entropy and a decrease of the
      flexibility in the denatured samples, respectively. The fractal model parameters
      strengthened the functional relevance of the flexibility of the protein chain.

PMID- 9777703
TI  - Differential scanning calorimetric study of poly(3-hydroxyoctanoate) inclusions
      in bacterial cells.
AB  - Medium chain length polyhydroxyalkanoates, MCL-PHAs, produced by bacteria as
      inclusion bodies or granules were analyzed in situ by differential scanning
      calorimetry (DSC) without isolation from the cells. The kinetic DSC study of PHA
      granules, which contained mostly 3-hydroxyoctanoate units (PHO), in Pseudomonas
      putida BM01 cells showed that the polymer within the granules existed in an
      amorphous state, but it crystallized after dehydration of the cells under freeze
      drying condition (below -50 degrees C) followed by annealing at ambient
      temperature. In this manner, PHO within the cells readily crystallized to the
      maximum degree of crystallinity within 24 h at room temperature, which was much
      faster than for the same polymer isolated by solvent extraction. This observation
      suggests that the polymer within the cellular granules may be well organized. The
      DSC endothermic melting peak areas for the room-temperature annealed polymers
      within the cells were directly proportional to the amount of polymer in the cell,
      and the results from this type of quantitative analysis were essentially
      identical to those obtained by gas chromatographic and gravimetric analysis of
      the polymers. X-Ray diffraction analysis of the polymer in the freeze-dried,
      whole cells and of the isolated, fully crystallized polymer showed that the two
      types of PHO samples had similar crystal structures, but the polymer in the
      granules exhibited better side-chain packing and higher crystallinity.

PMID- 9777704
TI  - On the helical conformation of un-ionized poly(gamma-D-glutamic acid).
AB  - The conformational preferences of the naturally occurring poly(gamma-D-glutamic
      acid) in the un-ionized state were investigated using a combination of molecular
      dynamics and quantum mechanical calculations. Results indicated that a left
      handed helix with 19-membered ring hydrogen bonds set between the CO of the amide
      group i and the NH of amide group i + 3 is the most stable conformation for this
      poly(gamma-amino acid). Weak intramolecular interactions between the oxygens of
      the carboxyl side groups and the NH of the backbone amide groups were detected.
      They are assumed to be responsible for the unexpected handedness exhibited by the
      helix with regards to the stereochemistry of the compound.

PMID- 9777705
TI  - Electrostatics of the phospholipase-membrane interaction.
AB  - The electrostatic interaction of the Phospholipase A2 (PLA2)-membrane complex in
      the presence and absence of calcium is analysed by the computation of the
      electrostatic profiles of the components and the complex. The electrostatic
      potential was computed by using of the program MOLPOT that implement the boundary
      element method to solve the electrostatic problem. It considers a closed surface
      in three dimensions that contains the macromolecule that follows as close as
      possible the macromolecule shape. The results show that the presence of calcium
      ions contributes to the stability of the complex and at the same time creates a
      favourable electrostatic potential pattern that may be favourable for the
      lipolysis of the membrane components.

PMID- 9777706
TI  - Thermodynamic and kinetic characterization of calf lens gammaF-crystallin.
AB  - Gamma-crystallin is reported to be conformationally stable because of its
      internal structural symmetry, and gammaF (gammaIVa) is the most stable among the
      various gamma-crystallin gene products. However, there is no detailed report on
      its thermodynamic and kinetic stability. In the present study, detailed unfolding
      of gammaF-crystallin was investigated by equilibrium and kinetics methods with
      fluorescence and far-UV CD spectroscopic measurements. The GdnHCl-induced
      unfolding curves probed by Trp emission maximum and intensity showed a sharp
      single-step transition. Upon widening the unfolding transition with the use of
      urea in 1.5 M GdnHCl, a more proper fit for thermodynamic analysis was obtained.
      GammaF-Crystallin underwent a straightforward two-state process (N <==> U)
      without showing any measurable amount of intermediate. The conformational
      stability, as measured by deltaG(D)H2O (approximately 9 kcal/mol), indicates that
      gammaF-crystallin is a very stable protein. The high activation energy
      deltaG++H2O (approximately 24 kcal/mol), calculated from unfolding kinetics
      monitored by far-UV CD at 218 nm, also indicates that the native and unfolded
      states are separated by a high activation energy barrier.

PMID- 9777708
TI  - Fourier analysis of electron micrographs of positively stained collagen fibrils:
      application to type I and II collagen typing.
AB  - Type I and II collagen (native-type) fibrils, positively stained with uranyl
      acetate, present typical periodic (D = 67 nm) cross-striation patterns. Although
      the two patterns are similar, the distributions of charged amino acids along the
      type I and II collagen molecules are different. After optical diffraction
      analysis or computer image processing of electron micrographs, different Fourier
      transforms were obtained from type I and II collagen fibrils, either as native
      fibrils or after in vitro reconstitution from purified molecules. With tissues
      such as tendon and cartilage, better results were obtained after mild trypsin
      treatment, which allowed better isolation and staining of the collagen fibrils.
      The main difference observed in the Fourier transforms was the presence in type
      II collagen fibrils of a strong tenth-order peak (corresponding to the tenth
      harmonic of the fundamental frequency). In order to discriminate between the two
      collagens, we measured the ratio (R) of the areas under the ninth- and tenth
      order peaks. In trypsin treated tissues, the distributions of these ratios were
      clearly separated: below 1.0 for type II collagen fibrils and above 1.5 for type
      I collagen fibrils. This method appears to be suitable for rapid typing of type I
      and II collagen fibrils and might be useful for determining the exact composition
      of fibrils in tissues, such as intervertebral discs, that contain these both
      types of collagen.

PMID- 9777707
TI  - Folding of SNase R begins early during synthesis: the conformational feature of
      two short N-terminal fragments of staphylococcal nuclease R.
AB  - To further understand the folding of nascent peptide during the early course of
      peptide synthesis, two short N-terminal fragments of staphylococcal nuclease R
      (SNase R), SNR52 and SNR79, were made by deleting 97 and 70 amino acid residues
      from the C-terminus. The conformations of SNR52 and SNR79 were studied by FTIR
      and far-ultraviolet CD. The results demonstrate that even the short N-terminal
      fragments of SNase R still have a certain amount of residual ordered secondary
      structure in the physiological condition. The ordered secondary structures were
      mainly assigned as beta-strands and turns, which corresponds well to the
      structures of the N-terminal part in the native protein. The conformational
      changes during unfolding and refolding in different concentrations of guanidine
      hydrochloride (GuHCl), monitored by far-ultraviolet CD and intrinsic
      fluorescence, show that the interaction between amino acid residues, which
      governs the formation of their conformation are not random. Considered together
      with earlier studies (Jing et al., Biochim Biophys Acta 1995;1250:189-196; Zhou
      et al., J Biochem 1996:120: 881-888), the results suggest that the folding of
      nascent peptide chains begins early in the synthesis process and that the amount
      of ordered structure increases with increasing peptide chain length until the
      conformation of the biologically active protein is generated.

PMID- 9777709
TI  - Thermal denaturation and renaturation of a fermentation broth of xanthan:
      rheological consequences.
AB  - The rheological properties of an unpasteurised and concentrated xanthan
      fermentation broth (c = 30 g/l 0.02 M in salt) were studied before heat treatment
      and after a thermal heating/cooling cycle performed at various polymer
      concentration conditions (10-30 g/l). At concentrations below 10 g/l heat
      denaturation occurs with dissociation of the native double-stranded structure
      into two single strands. At higher concentration, no complete dissociation
      happens. Changes in both viscoelastic properties and molecular weight are
      observed after heating above the melting order-disorder temperature (Tm). They
      are related to the order disorder conformational transition of the xanthan
      molecules. Xanthan renatured in concentrated conditions (above 10 g/l) has a
      higher viscosity than that of the native sample and displays more gel-like
      properties. The inhibition of the dissociation in two single strands in the high
      concentration range is attributed to the presence of nematic phases observed by
      viscoelastic measurements and apolar microdomains evidenced by the addition of a
      neutral detergent.

PMID- 9777710
TI  - Natural hepatocyte growth factor (HGF) from human serum and a bound form of
      recombinant HGF with heparan sulfate are indistinguishable in their
      physicochemical properties.
AB  - Natural hepatocyte growth factor (nHGF) purified from human serum showed a
      difference in molecular mass (Mr) between SDS PAGE (76-90 kDa) and gel filtration
      chromatography on a Sephadex G-200 column (> 200 kDa), whereas nHGF or
      recombinant HGF (rHGF) from cell culture medium did almost the same Mr (74-100
      kDa). A bound form of rHGF with heparan sulfate (or heparin), and an aggregate
      form of rHGF itself showed a homogeneous band with a Mr of 76-90 kDa on SDS PAGE,
      but showed a Mr larger than 200 kDa on a Sephadex G-200 column. Both nHGFs, rHGF
      and the bound form were basic, but the aggregate form was acidic in ionic nature.
      No significant difference was found in affinity for heparin among these HGF
      preparations. The bound form treated by the procedures for purification of nHGF
      from human serum still showed a larger molecular form. The bound form mimicked
      physicochemical properties of nHGF purified from human serum. These results
      suggest that a possible form of nHGF in human serum may be a bound form with
      heparin-like molecules such as heparan sulfate, which are found in the
      circulation and on cell surface, and purified as the bound form.

PMID- 9777711
TI  - Development of in vitro screening system for assessment of antifilarial activity
      of compounds.
AB  - Evaluation of antifilarial activity of new potential agents in vivo is extremely
      time consuming and uneconomic. In the present study effort has been made to
      develop an in vitro screening method using Acanthocheilonema viteae, a
      subcutaneously dwelling rodent filariid with anaerobic metabolic characteristics
      like human filariids, W. Bancrofti/Brugia malayi as test parasite. Motility test
      and tetrazolium (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide,
      MTT) based colorimetric assay were used as parameters in in vitro assay. Results
      showed that 92.3% of compounds (in vivo active) could be picked up in the in
      vitro assay when both adults and microfilarae (mf) were used simultaneously. Mf
      and adult stages separately detected, respectively, 84.6 and 69.2% of in vivo
      active compounds. The adults and mf separately and both the life stages together
      exhibited, respectively, 80.0, 50.0 and 80.0% false positive results in the in
      vitro test with in vivo inactive compounds. It is felt that mf stage when used in
      in vitro test using motility and MTT assays as parameters would be useful in
      primary screening of new potential filaricides.

PMID- 9777712
TI  - Schistosoma mansoni infection in owl monkeys (Aontus nancymai): evidence for the
      early elimination of adult worms.
AB  - Detailed parasitologic, serologic, clinical and histopathologic studies were
      conducted in owl monkeys (Aotus nancymai) exposed to varying numbers of cercariae
      of Schistosoma mansoni. All the experimental animals had clinical symptoms
      suggestive of infection (weight loss diarrhoea, mucus in stools, etc.) which were
      not seen in uninfected individuals. The only A. vociferans included in this study
      passed S. mansoni eggs 8 weeks after infection. None of the A. nancymai passed
      eggs in their faeces. No adult worms were recovered following perfusion of the
      sacrificed experimental monkeys, suggesting that they were early eliminated.
      Serological techniques (ELISA-SEA and COPT) allowed diagnosis of infection,
      starting 9 weeks post challenge, in all but one A. nancymai exposed to 100
      cercariae. Granulomas containing eggs were observed predominantly in liver and
      less extensively in intestine, suggesting that adult worms were mainly lodged in
      the intrahepatic portal system. We conclude that A. nancymai is susceptible to
      infection with S. mansoi, with the worms reaching sexual maturity, but being
      eliminated shortly after oviposition.

PMID- 9777713
TI  - Diagnostic evaluation of PCR on dried blood samples from goats experimentally
      infected with Trypanosoma brucei brucei.
AB  - In seven goats experimentally infected with a pleomorphic clone of Trypanosoma
      brucei brucei, parasitaemia was monitored weekly for 6 weeks by wet blood film
      and microhaematocrit buffy coat examination. Dried blood samples on filter paper
      were concomitantly collected and tested by PCR using three different primer sets,
      putatively specific for Trypanozoon, T. vivax and T. congolense. With the
      originally designed ORPHON5J Trypanozoon primers, PCR tests became positive after
      1 week (six animals) or 2 weeks (one animal) of infection and remained
      consistently positive until the end of the experiments, thus yielding an overall
      positivity rate of 97%, as compared with 74% for all parasitological tests
      together. The T. vivax and T. congolense primers yielded no positive PCR results.

PMID- 9777714
TI  - Triatoma infestans can be captured under natural climatic conditions using yeast
      baited traps.
AB  - The effectiveness of a trap for triatomines baited with yeast cultures has been
      previously demonstrated in laboratory assays. We report results from assays
      testing yeast-traps for Triatoma infestans performed under natural climatic
      conditions. All assays were conducted at experimental chicken-coops colonised by
      bugs, situated at an endemic area for Chagas disease in Argentina. Two different
      models of traps were tested, for use either on the floor, or attached to walls.
      The results obtained clearly demonstrate that yeast-baited traps are effective
      for capturing triatomine bugs. Floor traps, when baited, captured significantly
      more bugs than their controls (t-test, P = 0.0008, k = 10). In addition, wall
      traps were also more effective, when compared to their controls (t-test, P =
      0.011, k = 10). The maximum capture by a single yeast-trap was 39 bugs in one
      night, while for the same period the maximum capture by a control-trap was two
      bugs. Traps captured significantly more bugs at nights when maximum temperature
      was above 18 degrees C (t-test, P = 0.0002). Results indicate that yeast traps
      are capable of capturing significant numbers of free insects in one night. The
      potential use of yeast- traps for the detection of triatomine bugs is discussed.

PMID- 9777715
TI  - Malaria epidemiology, glucose 6-phosphate dehydrogenase deficiency and human
      settlement in the Vanuatu Archipelago.
AB  - Vanuatu is located at the southeast margin of the malarious band extending from
      southeast Asia to eastern Melanesia. We analysed the malaria situation on
      different islands of Vanuatu, using passive case detection and malariometric
      survey data from 1985 to 1992, i.e. after the DDT residual programme ceased and
      before the impregnated bed-nets programme started on a larger scale. Malaria was
      mainly hypo-mesoendemic but with hyperendemic spots in certain years and on some
      islands. The transmission was generally more intense in the northern islands than
      in the south. In the late 1980s, annual parasite incidence per one thousand
      population (API) was around 180. The overall parasite rate was 11.9% with
      Plasmodium falciparum, P. vivax and P. malariae rate of 5.2, 6.7, and 0.1%,
      respectively. There was a seasonal fluctuation of P. falciparum incidence,
      whereas the P. vivax incidence was rather stable. Vivax malaria was confined to
      children less than 10 years old, while the intense in the northern islands than
      in the south. In the late 1980s, annual parasite incidence per one thousand
      population (API) was around 180. The overall parasite rate was 11.9% with
      Plasmodium falciparum, P. vivax and P. malariae rate of 5.2, 6.7, and 0.1%,
      respectively. There was a seasonal fluctuation of P. falciparum incidence,
      whereas the P. vivax incidence prevalence of P. falciparum only changed
      moderately with age. The mean rate of glucose 6-phosphate dehydrogenase (G6PD)
      deficiency among male subjects was in 7.4% but with a wide variation of 0-14.3%
      on different islands. A positive rank-order correlation was found between malaria
      incidence and G6PD deficiency rate on the different islands. A reasonable
      hypothesis is that malaria was introduced to the islands with the first human
      settlement 4000 years ago, with a geographical malaria distribution similar to
      the present situation. Different malaria endemicities possibly then selected
      different prevalences of G6PD deficiency over many generations.

PMID- 9777716
TI  - Studies on immunodiagnosis of dracunculiasis. II. Search for circulating
      antigens.
AB  - Sera from individuals living in a dracunculiasis endemic area of northern Ghana
      were examined for circulating Dracunculus medinensis antigens by applying
      protocols previously developed for detection of circulating antigens in other
      helminth infections. Antisera from rabbits immunised with homogenized first stage
      D. medinensis larvae were used for antigen capture and detection in three
      different forms, namely non-treated, biotinylated and horseradish peroxidase
      (HRP)-labelled. Three different preparations of human sera were examined, namely
      non-treated, pre-treated with polyethylene glycol/ethylenediaminetetra-acetic
      acid (PEG/EDTA) for analysis of precipitated immune complexes, and pre-treated
      with trichloroacetic acid (TCA) for analysis of isolated glycoproteins. In both
      SDS-PAGE/Western blotting and ELISA, significant reactivity was observed between
      non-treated and treated rabbit-antisera on the one hand and non-treated and
      treated human sera on the other. However, no significant response differences
      were observed between sera obtained from individuals with dracunculiasis and non
      endemic controls. The reasons are analysed and possible explanations presented.
      The study provided no evidence that D. medinensis-specific circulating antigens,
      detectable by relatively simple means, occur in infected individuals.

PMID- 9777718
TI  - A review of the present status of lymphatic filariasis in Vietnam.
AB  - Establishing the current status of an infectious disease forms the starting point
      of any attempt at parasite control. Although data on the prevalence and
      distribution of lymphatic filariasis exist for Vietnam from the early 1900s, the
      present situation regarding the disease is less well-known. Here, we review the
      results of recent surveys conducted by the Institute of Malariology, Parasitology
      and Entomology, Hanoi, to update the existing information on filariasis
      epidemiology and distribution for this country. The present results are from
      surveys carried out on some 135,000 individuals in 24 provinces of Vietnam. The
      highest prevalences of microfilaraemia (primarily Brugia malayi ) are observed in
      lowland areas of the Red River Delta and in Quang-binh Province where the survey
      results show microfilaraemia (mf) prevalences in the range of 0.9-5.5%. The most
      common type of chronic clinical manifestation is shown to be leg elephantiasis. A
      significant finding is that an overall decrease in mf prevalence was observed to
      occur in five communities which were surveyed twice over an 11-21-year period,
      even though no interventions were carried out between the two surveys. The
      changes are probably caused by environmental changes, such as increased standards
      of housing and drainage. Studies on the effect of selective chemotherapy and mass
      chemotherapy using diethylcarbamazine showed reductions in community mf
      prevalences of 69 and 72-88%, respectively. Furthermore, cats do not appear to
      represent significant reservoirs of infection. These findings of geographical
      restriction of infection, effective and well-tolerated drug therapy, low
      significance of animal reservoirs, together with the existence of an effective
      national health network, suggest a good prognosis for the control of filariasis
      in this country.

PMID- 9777717
TI  - Evaluation of the safety, immunogenicity, and pharmacokinetic profile of a new,
      highly purified, heat-treated equine rabies immunoglobulin, administered either
      alone or in association with a purified, Vero-cell rabies vaccine.
AB  - A clinical evaluation of a new, purified, heat-treated equine rabies
      immunoglobulin (PHT-Erig), F(ab')2 preparation, was carried out in Thailand and
      in the Philippines-two countries where rabies is endemic. An initial prospective,
      randomised, controlled trial (Study 1), compared the safety and pharmacokinetics
      (serum concentrations of rabies antibodies) after administration either of PHT
      Erig or of a commercially-available, equine rabies immune globulin (Erig PMC). A
      second trial (Study 2) simulated post-exposure rabies prophylaxis by using a
      reference cell culture vaccine, the purified Vero-cell rabies vaccine (PVRV),
      administered in association with either Erig PMC or PHT-Erig. In Study 1, 27
      healthy, Thai adults received a 40 IU kg(-1) dose of either Erig PMC (n = 12) or
      PHT-Erig (n = 15) via the intramuscular (i.m.) route; half of the dose was
      injected into the deltoid area and the other half into the buttocks. Serum for
      rabies antibody determination and F(ab')2 concentration was collected at hours
      (H) 0, 6 and 12, and on day (D) 2, 3, 4, 6, 8, 10, 12 and 15. Both products were
      safe, with no serious adverse events, and in particular, no anaphylactic
      reactions or serum sickness was reported. A statistical comparison of the
      pharmacokinetic parameters did not demonstrate bioequivalence of the two
      products. Nonetheless, the relative bioavailability of 93% and the similar
      absorption rates suggest the pharmacokinetic profiles of Erig and PHT-Erig are
      similar. The antibody level in either group were low throughout the 15-day study
      period. The geometric mean titer (GMT) values ranged from group 0.027-0.117 IU
      ml(-1) in the Erig group and from 0.029 to 0.072 IU ml(-1) in the PHT-Erig. There
      was no significant difference between the evolution of GMT values for the two
      groups. In Study 2, 71 healthy volunteers received 40 IU kg(-1) via the
      intramuscular route of either Erig PMC (n = 36) or PHT-Erig (n = 35) on D0, in
      association with five doses of PVRV on D0, D3, D7, D14 and D28. The safety
      evaluation was performed during the 28-day follow-up and serum samples for anti
      rabies antibody titration were collected on D0 (before injection) D3, D7, D14 and
      D28. No serious reactions were reported in either group. In particular, no
      immediate (anaphylactic type) or delayed (serum sickness) allergic reactions were
      observed. Over the 28-day follow-up period, GMT profiles of the two groups were
      statistically equivalent. On D14, 100% of the subjects had protective antibody
      titers (anti-rabies antibodies > or = 0.5 IU ml(-1), which is the WHO-recommended
      level of seroconversion), and Erig PMC and PHT-Erig were indistinguishable
      according to the clinical definition chosen. On D28, the GMT values were 33.2 IU
      ml(-1) (95% CI, 23.8-46.1 IU ml(-1)) in the Erig PMC/PVRV group and 31.4 IU ml(
      1) (95% confidence interval, CI, 23.4-42.2 IU ml(-1)) in the PHT-Erig/PVRV group,
      showing evidence of adequate vaccine-induced antibody responses in both groups.
      The increased purity, the heat-treatment step introduced in the manufacturing
      process of PHT-Erig, and the good clinical results substantiate the use of this
      new generation, purified equine F(ab')2 preparation in the post-exposure
      prophylaxis of rabies.

PMID- 9777719
TI  - Increased sensitivity of the card agglutination test CATT/Trypanosoma brucei
      gambiense by inhibition of complement.
AB  - CATT/Trypanosoma brucei (T.b.) gambiense is an antibody detection test currently
      used in field surveys on Gambian sleeping sickness. The screening test is usually
      performed on a drop of freshly collected heparinized blood, followed by a more
      specific confirmation test on diluted blood, plasma or serum. This approach may
      be biased by the occurrence of a complement-mediated prozone phenomenon causing
      lower test sensitivity at lower sample dilutions. A simple remedy is by addition
      of a Ca2+ chelating agent such as EDTA.

PMID- 9777720
TI  - Investigations on the in vitro metacyclogenesis of a visceral and a cutaneous
      human strain of Leishmania infantum.
AB  - The in vitro metacyclogenesis of a visceral (VL) and cutaneous (CL) human strain
      of Leishmania infantum was monitored in order to find out the kinetics of this
      process and the in vitro infective capacity for macrophages of the metacyclic
      promastigotes developed. To identify, enumerate, and separate the metacyclic
      population, the complement-dependent lysis by normal serum and the agglutination
      by peanut agglutinin (PNA) were used, as they were shown to be useful for the
      purpose of this study. Maximum percentage of metacyclics was detected by both
      techniques on the 4th day of growth for VL and the 6th day for CL, and was higher
      for the VL strain. The in vitro infectivity for macrophages of two strains was
      assayed, and the high parasitization data obtained were transformed in order to
      determine the increase of the parasite burden for macrophages throughout the
      incubation time of the experiments (2-72 h post-infection (p.i.)). This parameter
      is denominated the infectivity ratio (%I) and calculated as follows: (number of
      intracellular parasites per infected macrophage at 'x' time p.i./number of
      intracellular parasites per infected macrophage at 2 h p.i.) x 100. When %I was
      calculated for promastigotes unagglutinated by PNA (PNA-)--metacyclic or
      infective promastigotes--at any time of culture, the %I at 72 h p.i. was always
      much higher than for agglutinated promastigotes (2.1-12.5 times)--non-infective
      promastigotes--and unfractionated promastigotes from culture (1.7-9.5 times),
      especially with VL parasites. Likewise, the %I for VL PNA- promastigotes from the
      4th day of culture was 1.9 times higher than for CL PNA- promastigotes from the
      6th day of culture. The higher resistance to lysis by serum, percentage of
      metacyclics (PNA-), and infectivity ratio of VL than CL could be related to a
      higher spreading capability into the host body associated with higher pathogenic
      effects of the visceral strain than the cutaneous one.

PMID- 9777721
TI  - Cysticidal effect of chlorine dioxide on Giardia intestinalis cysts.

PMID- 9777722
TI  - Susceptibility to trypanosomosis of three Bos indicus cattle breeds in areas of
      differing tsetse fly challenge.
AB  - Studies to assess the differences in susceptibility to trypanosomosis among Bos
      indicus cattle breeds (Maasai Zebu, Orma Boran and Galana Boran) were conducted
      under conditions of varying tsetse fly challenge at the Nguruman escarpment in
      south-western Kenya, for a period of 1 year. It was found that under tsetse
      challenge quantified as high, Maasai Zebu and Orma Boran were less susceptible
      than Galana Boran to trypanosome infections, as judged by the significantly lower
      incidence of infection, development of less severe anaemia, fewer requirements
      for trypanocidal drug treatments, higher growth rates and fewer mortalities. In
      the area where tsetse challenge was considered low as a result of a tsetse fly
      control operation using odour-baited traps, only the Maasai Zebu and Orma Boran
      were compared. No significant differences in the incidence of infection, degree
      of anaemia or growth rates were observed between the two breeds, but all were
      significantly different from their counterparts in the high tsetse challenge
      area. These results suggest that there is variation in resistance to
      trypanosomosis among Bos indicus cattle breeds that could be exploited as part of
      the integrated trypanosomosis control programmes in East Africa.

PMID- 9777723
TI  - A multiple antigen ELISA to detect Neospora-specific antibodies in bovine sera,
      bovine foetal fluids, ovine and caprine sera.
AB  - Neospora caninum is a cyst-forming coccidian parasite recently identified as a
      cause of abortion in cattle. The epidemiology of neosporosis is poorly
      understood, partly because accurate diagnosis of infection is difficult. In this
      paper we describe the development of a multiple antigen-based enzyme-linked
      immunosorbent assay (ELISA) to detect antibodies to N. caninum in sera from
      cattle, sheep and goats as well as from bovine foetal fluids. A water-soluble
      fraction (wsf) of sonicated NC-1 strain tachyzoites was used as the antigen in
      the ELISA. Minimum optical density (OD) values that were considered to be
      Neospora antibody-positive, that is, the cut-off OD values were determined
      separately for bovine maternal sera, bovine foetal fluids, ovine sera and caprine
      sera; they were 0.40, 0.17, 0.23 and 0.41 OD, respectively. The ELISA gave a high
      signal/noise ratio, giving good sensitivity and specificity, correlating well
      with the indirect fluorescent antibody test (IFAT) currently used to diagnose
      Neospora infection in cattle, sheep and goats. In both the ELISA and immunoblot
      analysis using the same antigen, there was no significant cross-reactivity with
      sera from cattle, sheep or goats that had been infected with Toxoplasma gondii.
      The ELISA also showed no cross-reactivity in sera from cattle infected with
      Sarcocystis cruzi, Babesia divergens, B. bovis and B. bigemina. The wsf fraction
      of sonicated N. caninum tachyzoites used in this ELISA can be easily prepared and
      may be more sensitive than a single antigen ELISA, whilst still retaining good
      specificity.

PMID- 9777724
TI  - Modelling the prevalence of Echinococcus and Taenia species in small ruminants of
      different ages in northern Jordan.
AB  - A base-line survey of Echinococcus granulosus, Taenia hydatigena and T ovis were
      undertaken in order to investigate the transmission dynamics of these parasites
      in northern Jordan. Intensity of E. granulosus infection, in sheep, increased
      with age in a linear fashion whilst the asymptotic prevalence was one. This
      implied that E. granulosus is in an endemic steady state with no evidence of
      protective immunity in the intermediate host. The mean number of cysts increased
      by 1.66 per year with approximately 0.320 infections per year, each infection
      consisting of 598 eggs to produce 5.2 cysts. The basic reproduction ratio (R0)
      was estimated to be 1.5-1.8. A similar pattern was suggested with E. granulosus
      in goats but the infection pressure appeared to be lower with only 0.128 cysts
      per year. Although infection in goats appeared to be endemic there was some
      evidence of departure from the model which might indicate that the model needs
      adjusting for this species. In the case of T. hydatigena the host age-intensity
      helminth distribution indicated that this parasite was hyperendemic in both sheep
      and goats, implying regulation by intermediate host immunity. Consequently, R0
      was determined from asymptotic prevalence curves for T hydatigena and was
      calculated to be 4.0 and 3.1 in sheep and goats, respectively. The lower R0 in
      goats, together with the higher asymptotic age-intensity and age-prevalences,
      indicates that goats acquire immunity more slowly to T hydatigena in comparison
      to sheep. Taenia ovis was not detected in any animals.

PMID- 9777725
TI  - Resistance of Galla and Small East African goats in the sub-humid tropics to
      gastrointestinal nematode infections and the peri-parturient rise in faecal egg
      counts.
AB  - A study was carried out from 1994 to 1996 to compare the resistance to naturally
      acquired gastrointestinal (GI) nematode infections (predominantly Haemonchus
      contortus) of 88 Galla and 114 Small East African (SEA) goats (does) in the sub
      humid coastal region of Kenya. Live weights (LWT), blood packed cell volume (PCV)
      and faecal egg counts (FEC) were recorded each year at mating, 3-4 months after
      mating, 1-2 weeks before kidding and 1-4 months after kidding. There was a
      significant increase in FEC and a decline in PCV in lactating does compared to
      non-lactating does over the peri-parturient period. This peri-parturient rise in
      FEC occurred in both breeds but was more marked and persistent in the Galla than
      in the SEA. The SEA does were more resistant to GI nematode infections than Galla
      does as shown by their significantly lower FEC and higher PCV at all sampling
      times over the reproductive cycle, but this breed difference was particularly
      marked over the lactation period.

PMID- 9777726
TI  - An annotated checklist by genus and species of 93 species level names for 51
      recognized species of small strongyles (Nematoda: Strongyloidea: Cyathostominea)
      of horses, asses and zebras of the world.
AB  - The results of an international collaborative effort to prepare a recommended
      list of scientific names for the small strongyles (Nematoda: Strongyloidea:
      Cyathostominea) of horses, donkeys and zebras are reported. Fifty-one valid
      species are recognized in 13 genera, including Cyathostomum, Coronocyclus,
      Cylicodontophorus, Cylicocyclus, Cylicostephanus, Skrjabinodentus,
      Tridentoinfundibulum, Petrovinema, Poteriostomum, Parapoteriostomum, Hsiungia,
      Cylindropharynx and Caballonema. In addition, 42 other species level names are
      listed as synonyms of the 51 recognized species or as species inquirendae (10
      species) or nomen nudum (one species). Numerous annotations provide information
      on the nomenclatural and systematics history, current status and additional
      studies needed.

PMID- 9777727
TI  - Development and survival of infective larvae of nematode parasites of sheep on
      pasture in a cool tropical environment.
AB  - The development and survival of nematode parasites of sheep were studied in a
      cool tropical environment of the highlands of Ethiopia on 24 plots serially
      contaminated with Haemonchus contortus, Longistrongylus elongata and
      Trichostrongylus colubriformis eggs over a period of 2 consecutive years from
      June 1993 to May 1995. The availability of infective larvae was monitored by
      monthly pasture sampling and larvae recovery. Infective larvae were recovered
      from the herbage collected from the plots contaminated in June, July, August,
      September and October of both years. The longevity of infective larvae varied
      between two and six weeks when eggs were deposited on pasture in June and
      October, respectively. During the dry and short rainy season (November through
      May), eggs failed to develop into L3 stage. It is suggested that the long period
      (7 to 8 months) of lack of development of trichostrongylid infective larvae on
      the pasture can be efficiently used in a strategic treatment programme to
      interrupt transmission of H. contortus, L. elongata and T. colubriformis in sheep
      in this environment.

PMID- 9777728
TI  - Development of electrical excitability: mechanisms and roles.

PMID- 9777729
TI  - Monitoring early neuronal differentiation by ion channels in ascidian embryos.
AB  - According to the evolutionary tree proposed by Garstang, the tunicate larva has a
      central role in directing the ancestral sessile animal derived from primitive
      echinoderms into the stem for vertebrates by evolution through neoteny. The close
      similarity of the tunicate larval body plan to those of vertebrates and the
      extraordinary simplicity indicated by an extremely small cell population make the
      ascidian embryo and larva an excellent model system for analysis of vertebrate
      embryonic development. Furthermore, isolated anterior animal blastomeres from the
      Halocynthia eight-cell cleavage-arrested embryo, which are known to include
      presumptive brain vesicle region, autonomously develop long-lasting Ca-dependent
      action potentials which are characteristic of epidermal differentiation. However,
      when blastometeres are cultured in contact with the anterior vegetal blastomere,
      which are known to include presumptive notochordal region, and raised in
      contacted two cell systems, the same anterior animal blastomeres now develop
      neuronal Na+ spikes characterized by expression of Na+ channels and
      triethylammonium sensitive delayed rectifier K+ channels. This unique two-cell
      system enables us to examine roles of cell contact in various aspects of
      inductive differentiation at the cellular level. In this review, we focus on this
      simple cellular preparation and in particular, attempt to show how to make the
      preparation.

PMID- 9777731
TI  - Regulation of voltage-gated K+ channel expression in the developing mammalian
      myocardium.
AB  - As in neurons, depolarization-activated, Ca2+-independent outward K+ currents
      play prominent roles in shaping the waveforms of action potentials in myocardial
      cells. Several different types of voltage-gated K+ currents that contribute to
      the distinct phases of action potential repolarization have been characterized in
      myocardial cells isolated from different species, as well as in cells isolated
      from different regions of the heart in the same species. Important among these
      are the transient outward current, I(to), similar to the neuronal K+ current IA,
      and several components of delayed rectification, including I(Kr)[IK(rapid)],
      I(Ks)(IK(slow)], and I(Kur)[IK(ultrarapid)]. The properties of these currents in
      different species and cell types are remarkably similar, suggesting that the
      molecular correlates of functional voltage-gated K+ channel types are also the
      same. A number of voltage-gated K+ channel (Kv) pore-forming (alpha) and
      accessory (beta) subunits have now been cloned from heart cDNA libraries, and a
      variety of experimental approaches are being exploited to determine the molecular
      relationships between these subunits and functional voltage-gated myocardial K+
      channels. Considerable progress has been made recently in defining these
      relationships, and the results obtained to date indeed suggest that distinct
      molecular entities underlie the different types of voltage-gated K+ channels
      characterized electrophysiologically in myocardial cells. Marked changes in the
      densities and/or the properties of voltage-gated K+ currents occur during normal
      cardiac development, as well as in conjunction with myocardial damage or disease,
      and there is considerable interest in understanding the molecular mechanisms
      underlying these changes. Although there is evidence for transcriptional,
      translational, and posttranslational regulation of functional voltage-gated K+
      channel expression, we are only beginning to understand the underlying
      mechanisms; further studies focussed on delineating the molecular mechanisms
      controlling functional K+ channel expression are clearly warranted.

PMID- 9777730
TI  - Role of cell-cell interactions in the developmental regulation of Ca2+-activated
      K+ currents in vertebrate neurons.
AB  - The functional expression of the Ca2+-activated K+ current (IK[Ca]) is dependent
      on cell-cell interactions in developing chick autonomic neurons. In chick ciliary
      ganglion (CG) neurons, expression of macroscopic IK[Ca] coincides with the
      formation of synapses with target tissues. CG neurons that develop in vivo in the
      absence of normal target tissues fail to express functional IK[Ca], although
      voltage-activated Ca2+ currents and most other ionic currents are expressed at
      normal amplitudes and densities. CG neurons placed in cell culture prior to
      formation of synapses with target tissues also fail to express macroscopic
      IK[Ca]. However, CG neurons cultured in the presence of a heat- and trypsin
      sensitive extract of target tissues express IK[Ca] at normal levels. Similarly,
      interactions with target tissue appear to regulate the expression of whole-cell
      IK[Ca] in developing chick sympathetic ganglion neurons, although the relevant
      trophic factors appear to be different from those required by CG neurons. In
      addition to target tissue interactions, an intact preganglionic innervation is
      required for the normal in vivo development of IK[Ca] in chick CG neurons. The
      trophic effects of the afferent innervation do not require synaptic activation of
      the CG neurons, indicating secretion of a trophic factor, possibly an isoform of
      beta-neuregulin. The results are consistent with the hypothesis that target- and
      nerve terminal-derived trophic factors interact at a posttranslational level in
      the regulation of a functional IK[Ca]. Together, this body of data demonstrates
      an essential role for cell-cell interactions in the differentiation of neuronal
      excitability.

PMID- 9777732
TI  - Dynamic regulation of K+ channel gene expression in differentiated cells.
AB  - Recent studies have determined that K+ channel gene expression is dynamically
      controlled in endocrine, cardiac, and neuronal cells. This regulation is induced
      by physiological stimuli (e.g., hormones, transmitters, depolarization), drugs
      (e.g., opiates) and with pathophysiological conditions (e.g., seizures,
      hypertension). In many cases, alterations in subunit expression are driven by
      transcriptional changes. Furthermore, resultant changes in excitability can be
      produced within hours because of the rapid turnover of Kv-channel proteins.
      Finally, the consequences of altering K+-channel subunit are complex because a
      single gene product can participate in forming functionally distinct homomeric
      and heteromeric channels in the same cell. Thus, regulating K+-channel genes
      constitutes a novel mechanism for producing intricate long-term changes in
      excitability.

PMID- 9777733
TI  - When, where, and how much? Expression of the Kv3.1 potassium channel in high
      frequency firing neurons.
AB  - The Kv3.1 potassium channel gene is expressed in neurons that fire action
      potentials at high frequencies. Neurons that express this gene, such as auditory
      brain stem neurons, have high-threshold voltage-dependent potassium currents that
      activate and deactivate unusually rapidly, and whose characteristics match those
      of the Kv3.1 subunit expressed heterologously. The level of Kv3.1 expression in
      neurons is regulated during development and by environmental stimuli.
      Pharmacological and computer modeling studies indicate that changes in the level
      of this channel alter the ability of a neuron to follow synaptic inputs at high
      frequencies. To understand the transcriptional mechanisms that control Kv3.1
      expression, an initial characterization of the primary promoter for the Kv3.1
      gene was carried out. This review summarizes current knowledge regarding Kv3.1
      gene transcription and the roles of upstream regulatory elements in conferring
      cell-type specificity and long-term regulation by extrinsic factors.

PMID- 9777734
TI  - Ion channel redistribution and function during development of the myelinated
      axon.
AB  - The development of myelinated axons represents one of the most complex
      interactions among different cell types in the nervous system. Striking changes
      occur in both morphology and function in the early postnatal period. Myelination
      effectively isolates electrically most of the axolemma and dramatically alters
      the pathways for current flow that are required for rapid, reliable, and
      efficient conduction. Correspondingly, ion channels must be directed to and
      stabilized at their required sites. In the case of Na+ channels, this requires a
      25-fold increase in density within nodes of Ranvier, and, in mammalian fibers, a
      virtually complete spatial separation from voltage-dependent K+ channels. Nodes
      must also be properly spaced to ensure a high conduction velocity and energy
      efficiency without compromising the safety factor for reliable propagation. In
      this review, we consider the events responsible for axon development, emphasizing
      the involvement of ion channels. We discuss the current state of research in this
      area, including some controversies regarding mechanisms of neuron-glial
      communication.

PMID- 9777735
TI  - Control of spontaneous activity during development.
AB  - Electrical activity participates in the development of the nervous system and
      comes in two general forms. Use-dependent or experience-driven activity occurs
      relatively late in development, and is important in events of terminal nervous
      system differentiation, such as stabilization of synaptic connections. Earlier in
      development, activity is spontaneous, occurring independently of normal sensory
      input and motor output. Spontaneous activity participates in many of the initial
      events of axon outgrowth, pruning of synaptic connections, and maturation of
      neuronal signaling properties. Despite its importance, the genesis of spontaneous
      activity is poorly understood. What is clear is that spontaneous activity must be
      regulated by the patterns with which voltage- and ligand-gated ion channels
      develop in individual neurons. This review explores how that regulation most
      likely occurs.

PMID- 9777736
TI  - Orchestration of neuronal migration by activity of ion channels, neurotransmitter
      receptors, and intracellular Ca2+ fluctuations.
AB  - The real-time observation of cell movement in acute cerebellar slices reveals
      that granule cells alter their shape concomitantly with changes in the mode and
      rate of migration as they traverse different cortical layers. Although the origin
      of local environmental cues responsible for these position-specific changes in
      migratory behavior remains unclear, several signaling mechanisms involved in
      controlling granule cell movement have emerged. The onset of one such mechanism
      is marked by the expression of voltage-gated ion channels and neurotransmitter
      receptors in postmitotic cells prior to the initiation of their migration.
      Granule cells start their radial migration after the expression of N-type Ca2+
      channels and the N-methyl-D-aspartate subtype of glutamate receptors on the
      plasmalemmal surface. Blockade of the channel or receptor activity significantly
      decreases the rate of cell movement, indicating that the activation of these
      membrane constituents provides an essential signal for the translocation of
      granule cells. Another signal that controls the rate of cell migration is
      embedded in the combined amplitude and frequency components of Ca2+ fluctuations
      in the somata of migrating granule cells. Interestingly, each phase of Ca2+
      fluctuation controls a separate phase of saltatory movement in the granule cells:
      The cells move forward during the phase of transient Ca2+ elevation and remain
      stationary during the troughs. Consequently, the changes in the amplitude and
      frequency components of Ca2+ fluctuations directly affect granule cell movement:
      Reducing the amplitude or frequency of Ca2+ fluctuations slows down the speed of
      cell movement, while the enhancement of these components accelerates migration.
      These findings suggest that signaling molecules present in the local cellular
      milieu encountered on the migratory route control the shape and motility of
      granule cells by modifying Ca2+ fluctuations in the soma through the activation
      of specific ion channels and neurotransmitter receptors.

PMID- 9777737
TI  - Mechanisms of spontaneous activity in developing spinal networks.
AB  - Developing networks of the chick spinal cord become spontaneously active early in
      development and remain so until hatching. Experiments using an isolated
      preparation of the spinal cord have begun to reveal the mechanisms responsible
      for this activity. Whole-cell and optical recordings have shown that spinal
      neurons receive a rhythmic, depolarizing synaptic drive and experience rhythmic
      elevations of intracellular calcium during spontaneous episodes. Activity is
      expressed throughout the neuraxis and can be produced by different parts of the
      cord and by the isolated brain stem, suggesting that it does not depend upon the
      details of network architecture. Two factors appear to be particularly important
      for the production of endogenous activity. The first is the predominantly
      excitatory nature of developing synaptic connections, and the second is the
      presence of prolonged activity-dependent depression of network excitability. The
      interaction between high excitability and depression results in an equilibrium in
      which episodes are expressed periodically by the network. The mechanism of the
      rhythmic bursting within an episode is not understood, but it may be due to a
      "fast" form of network depression. Spontaneous embryonic activity has been shown
      to play a role in neuron and muscle development, but is probably not involved in
      the initial formation of connections between spinal neurons. It may be important
      in refining the initial connections, but this possibility remains to be explored.

PMID- 9777738
TI  - Intracellular calcium regulation of channel and receptor expression in the
      plasmalemma: potential sites of sensitivity along the pathways linking
      transcription, translation, and insertion.
AB  - Nervous system development is "activity dependent"--activation of neurons
      controls their development, which controls their activation patterns, which will
      then influence their further development, and so on. A critical issue is thus the
      regulation of channel and receptor expression. For nerve cells, the presence of
      specialized Ca2+-permeable channels in the surface membrane provides a direct
      link between electrical activity and the intracellular Ca2+ ion concentration
      ([Ca2+]i), and in many instances [Ca2+]i is thought to link membrane activation
      and internal biosynthesis. In this context, Ca2+-permeable channels function as
      "activity sensors," transducing membrane activation by admitting Ca2+ rapidly,
      locally, and proportionately. In this review, I consider the potential of [Ca2+]i
      to regulate channel and receptor expression. I emphasize mechanisms by which the
      Ca2+ concentration of the cytosol and/or the Ca2+ concentrations of membrane
      delimited Ca2+ sequestering organelles may influence biosynthetic processes.
      Here, I use "expression" in the most general sense of referring to the number and
      location of functional channels and receptors in the plasmalemma; regulation of
      expression is not limited to transcriptional regulation, but further encompasses
      translational and posttranslational processes. At the core is the notion of
      regulation by patterned oscillations in cytosolic [Ca2+], and, in a synchronous
      or contrapuntal manner, filling and depletion of a series of Ca2+-sequestering
      organelles--nuclear envelope, endoplasmic reticulum, Golgi, trans-Golgi network,
      and secretory vesicles--that all also have critical roles in biosynthesis of
      membrane proteins. These structures provide both an internal Ca2+ regulation and
      distribution system, and a scaffold for synthesis, targeting, and insertion of
      channels and receptors.

PMID- 9777739
TI  - Effects of ion channel activity on development of dorsal root ganglion neurons.
AB  - Studies of mouse dorsal root ganglion neurons in vitro demonstrate that ion
      channel function and regulation can influence a wide range of developmental
      processes. The work suggests that much as exposure to different trophic factors,
      the pattern of impulse activity a neuron experiences can have significant
      structural and functional effects during development. Studies concerning effects
      of ion channel activity on growth cone motility, axon fasciculation, synaptic
      plasticity, myelination, and intracellular signaling pathways regulating gene
      expression are presented in the context of changes in endogenous firing patterns
      during development.

PMID- 9777740
TI  - Ca2+ channel-regulated neuronal gene expression.
AB  - Neuronal activity is required for the survival of specific populations of
      neurons, for the proper synaptic organization of the visual and somatosensory
      cortex, and for learning and memory. The biochemical mechanisms that couple brief
      neuronal activity to rapid and lasting adaptive changes within the nervous system
      are poorly understood. Over a decade ago, it was first shown that mimicking
      neuronal activity by membrane depolarization rapidly induced the expression of a
      class of genes known as immediate early genes. Subsequently, it has been shown
      that neuronal activity triggers a temporal sequence of gene expression that has
      been suggested to play a role in mediating long-term adaptive responses. A major
      mechanism coupling neuronal electrical activity and the intracellular biochemical
      processes that culminate in gene expression is Ca2+ influx through plasma
      membrane Ca2+ channels. In this review, we delineate some of the reported
      mechanisms by which Ca2+ regulates gene expression: from its ability to activate
      specific intracellular signal transduction pathways to its ability to regulate
      the initiation, elongation, and translation of RNA transcripts. We will discuss
      some known mechanisms by which different patterns of Ca2+ influx, or Ca2+ influx
      through different types of channel, could generate distinct patterns of gene
      expression and how our understanding of Ca2+-regulated gene expression relates to
      larger questions of activity-dependent nervous system function.

PMID- 9777741
TI  - Development of electrical excitability in embryonic neurons: mechanisms and
      roles.
AB  - Xenopus spinal neurons serve as a nearly ideal population of excitable cells for
      study of developmental regulation of electrical excitability. On the one hand,
      the firing properties of these neurons can be directly examined at early stages
      of differentiation and membrane excitability changes as neurons mature.
      Underlying changes in voltage-dependent ion channels have been characterized and
      the mechanisms that bring about these changes are being defined. On the other
      hand, these neurons have been shown to be spontaneously active at stages when
      action potentials provide significant calcium entry. Calcium entry provokes
      further elevation of intracellular calcium via release from intracellular stores.
      The resultant transient elevations of intracellular calcium encode
      differentiation in their frequency. Recent studies have shown that different
      neuronal subpopulations enlist distinct mechanisms for regulation of excitability
      and recruit specific programs of differentiation by particular patterns of
      activity.

PMID- 9777742
TI  - Thyrotropin suppression and disease progression in patients with differentiated
      thyroid cancer: results from the National Thyroid Cancer Treatment Cooperative
      Registry.
AB  - The ideal therapy for differentiated thyroid cancer is uncertain. Although
      thyroid hormone treatment is pivotal, the degree of thyrotropin (TSH) suppression
      that is required to prevent recurrences has not been studied in detail. We have
      examined the relation of TSH suppression to baseline disease characteristics and
      to the likelihood of disease progression in a cohort of thyroid cancer patients
      who have been followed in a multicenter thyroid cancer registry that was
      established in 1986. The present study describes 617 patients with papillary and
      66 patients with follicular thyroid cancer followed annually for a median of 4.5
      years (range 1-8.6 years). Cancer staging was assessed using a staging scheme
      developed and validated by the registry. Cancer status was defined as no residual
      disease; progressive disease at any follow-up time; or death from thyroid cancer.
      A mean TSH score was calculated for each patient by averaging all available TSH
      determinations, where 1 = undetectable TSH; 2 = subnormal TSH; 3 = normal TSH;
      and 4 = elevated TSH. Patients were also grouped by their TSH scores: group 1:
      mean TSH score 1.0-1.99; group 2: mean TSH score 2.0-2.99; group 3: mean TSH
      score 3.0-4.0. The degree of TSH suppression did not differ between papillary and
      follicular thyroid cancer patients. However, TSH suppression was greater in
      papillary cancer patients who were initially classified as being at higher risk
      for recurrence. This was not the case for follicular cancer patients, where TSH
      suppression was similar for all patients. For all stages of papillary cancer, a
      Cox proportional hazards model showed that disease stage, patient age, and
      radioiodine therapy all predicted disease progression, but TSH score category did
      not. However, TSH score category was an independent predictor of disease
      progression in high risk patients (p = 0.03), but was no longer significant when
      radioiodine therapy was included in the model (p = 0.09). There were too few
      patients with follicular cancer for multivariate analysis. These data suggest
      that physicians use greater degrees of TSH suppression in higher risk papillary
      cancer patients. Our data do not support the concept that greater degrees of TSH
      suppression are required to prevent disease progression in low-risk patients, but
      this possibility remains in high-risk patients. Additional studies with more
      patients and longer follow-up may provide the answer to this important question.

PMID- 9777743
TI  - Comparison of thyroid peroxidase expression with cellular proliferation in
      thyroid follicular tumors.
AB  - Thyroid cancer is associated with abnormal thyroid peroxidase (TPO) expression as
      shown by abolition of immunodetection by monoclonal antibody 47 (Mab 47). The
      purpose of this study was to determine the relation of this abnormality with
      differentiation and proliferative potential of follicular tumors evaluated by
      analyzing thyroglobulin (TG) expression and proliferative cell nuclear antigen
      (PCNA) index. TPO, TG, and PCNA immunostaining were performed in a series of 30
      thyroid follicular tumors ranging from adenoma to invasive carcinoma. Our
      findings confirmed that TPO abnormalities and PCNA index were correlated with
      malignancy, and that PCNA as well as TPO could be used to determine the growth
      potential of follicular proliferations in fine-needle aspirates. The most
      discriminant parameter was the ratio between the percentage of Mab-47 and PCNA
      positive cells. Ratios under 0.6 were correlated with malignancy in 90% of the
      cases, with only 3 cases of atypical adenomas being misdiagnosed as carcinomas.
      An inverse correlation was found between TPO and PCNA expression, but TG, which
      persisted at high levels in several actively growing follicular carcinomas, did
      not appear directly linked to cellular proliferation. These findings confirm
      that, unlike a decrease in TG synthesis that merely reflects the progressive loss
      of differentiation occurring in high-grade proliferations, alteration of TPO is
      an early marker of thyroid follicular tumors, closely related to acceleration of
      tumor growth in the first stages of malignant transformation.

PMID- 9777744
TI  - Cancer risk in individuals with benign thyroid disorders.
AB  - The risk of cancer was examined in a cohort of 57,326 individuals who were
      discharged from a Danish hospital with a diagnosis of myxedema, thyrotoxicosis,
      or goiter. Although the general risk of cancer was only slightly increased, the
      risk of several sites was significantly above expected. The risk of thyroid
      cancer especially, was increased with standardized incidence ratios among women
      of 2.1 (myxedema), 2.5 (thyrotoxicosis), and 6.6 (nontoxic goiter). The increase
      in risk was present even many years after discharge, indicating that surveillance
      was not the only explanation. Furthermore, an increased risk was noted for cancer
      of the kidney in women discharged with myxedema (standardized incidence ratios
      [SIR] = 1.8) and thyrotoxicosis (SIR = 1.3), for cancer of the bladder in women
      discharged with myxedema (SIR = 1.5) and nontoxic goiter (SIR = 1.3), and for
      cancer of the hematopoetic system in women discharged with myxedema (SIR = 1.4)
      and nontoxic goiter (SIR = 1.4). The findings indicate that thyroid disorders may
      be related to cancer risk of several specific sites other than the thyroid.

PMID- 9777745
TI  - Thyrocyte class I and class II upregulation is a secondary phenomenon and does
      not contribute to the pathogenesis of autoimmune thyroid disease.
AB  - It has been proposed elsewhere that thyrocyte (TEC) class I expression plays a
      central role in the pathogenesis of autoimmune thyroid disease (AITD). We have
      studied thyroid xenografts from patients with Graves' disease (GD) and normal
      (paranodular) (N) tissues in nude and severe combined immunodeficient (SCID)
      mice. TEC class I and II expression are markedly increased in GD, as compared
      with N thyroids. When these tissues are transplanted to nude mice in which the
      immune environment is deleted from the thyroid grafts, TEC class I and class II
      expression decline to low levels; interferon-gamma (IFN-gamma) but not interferon
      alpha (IFN-alpha) will then upregulate TEC class I and class II expression in
      these N and GD nude xenografts. In SCID mouse xenografts, GD tissue shows higher
      TEC class I and II expression compared with N. In these SCID mice, both IFN-alpha
      and IFN-gamma will stimulate TEC class I and II expression further in both GD and
      N. However, only IFN-alpha increases thyroid antibody (TAb) production from GD
      SCID grafts, whereas IFN-gamma causes a rise in GD TEC class I and II expression,
      but no significant increase in TAb. Moreover, in N SCID grafts, despite a rise in
      TEC class I and II expression induced by both IFNs, no TAb could be detected.
      Because an immune environment is necessary for TEC class I and II upregulated
      expression, we conclude that such upregulation is a secondary phenomenon. Because
      there was dissociation between the stimulation of TEC class I and II expression
      versus the production of TAb, then at least under these experimental conditions,
      there is no support for a role for TEC class I and class II upregulation in the
      pathogenesis of AITD.

PMID- 9777746
TI  - Glucose metabolism of the thyroid in Graves' disease measured by F-18-fluoro
      deoxyglucose positron emission tomography.
AB  - The radiolabeled glucose surrogate F-18-fluoro-deoxyglucose (F-18-FDG) and
      positron emission tomography (PET) were used to measure glucose metabolism of the
      thyroid in vivo. We evaluated patients with Graves' disease before therapy with
      radioiodine in comparison to patients with normal thyroids. Thirty-six patients
      with Graves' disease underwent scanning the day before radioiodine therapy.
      Twenty patients with head tumors and normal thyroids were the controls. Overall F
      18-FDG uptake was determined for all thyroids and modeling of glucose metabolism
      was performed in order to differentiate between glucose concentration in the
      fractional blood volume, glucose transport, and glucose utilization. F-18-FDG
      uptake was significantly higher in Graves' disease patients compared with
      controls. In these patients F-18-FDG uptake increased with increasing antithyroid
      antibodies and shorter radioiodine half-life. Modeling of glucose metabolism
      revealed substantial differences in thyroid F-18-FDG utilization constants (k3
      values) corresponding to enhanced local metabolic rates in Graves' disease. No
      significant differences in the remaining rate constants and the fractional blood
      volume were detected. These results indicate that glucose metabolism is enhanced
      in the thyroid of Graves' disease patients not only due to enhanced fractional
      blood volume but to enhanced utilization. Whether a lymphocytic infiltration or
      thyroid epithelial cells utilize this surplus of glucose cannot be determined
      using in vivo PET measurements in humans. Still, the correlation of radioiodine
      half-life and glucose hypermetabolism suggests direct or nondirect connections of
      glucose metabolism and hormone synthesis in thyroid cells.

PMID- 9777747
TI  - Body mass and body composition after total thyroidectomy for benign goiters.
AB  - To date there are no data available as to whether postmenopausal women who
      undergo total thyroidectomy for benign euthyroid goiter demonstrate changes in
      body mass or body composition. We prospectively evaluated 8 postmenopausal women
      (mean age 57 +/- 7; range 48 to 70 years) who underwent total thyroidectomy for
      benign goiter. All patients were euthyroid preoperatively (serum free thyroxine
      [FT4] 12.7 +/- 0.6 pmol/L and serum thyrotropin [TSH] 0.98 +/- 0.2 mU/L) and were
      commenced on adequate thyroxine replacement immediately postoperatively in order
      to maintain a serum TSH within the normal range (0.5-4 mU/L). Body mass, body
      composition, and thyroid function were assessed preoperatively, and at 4 and 12
      months postoperatively. Body composition was assessed by anthropometry and dual
      energy x-ray absorptiometry (Lunar DPX-L scanner). Eight healthy postmenopausal
      women without evidence of thyroid disease matched for age, weight, and estrogen
      therapy who were followed over the same period were used as controls. All
      patients were maintained in a euthyroid status throughout the study. No
      significant changes in body mass or any parameter of body composition were
      demonstrated at 4 and 12 months postoperatively. Similar findings were recorded
      in our control group. We conclude that total thyroidectomy in euthyroid
      postmenopausal women with benign goiter does not result in a significant change
      in either body mass or body composition if adequate thyroxine replacement is
      maintained.

PMID- 9777749
TI  - Papillary thyroid carcinoma, parathyroid adenoma, and unexplained
      hypercalcitoninemia: an unusual presentation of multiple endocrine neoplasia type
      2A?
AB  - Multiple endocrine neoplasia type 2 (MEN 2) is a rare syndrome of medullary
      thyroid carcinoma (MTC) with pheochromocytoma and/or primary hyperparathyroidism
      (PHP), usually due to multigland hyperplasia. MEN 2 is associated with several
      RET protooncogene mutations. A 61-year-old woman with a family history of RET
      positive MTC presented with a solitary thyroid nodule. Fine-needle aspiration
      biopsy was suspicious for neoplasm. Biochemical studies revealed basal
      hypercalcitoninemia (116 pg/mL [normal <26]) and PHP (serum calcium, 10.9 mg/dL;
      intact PTH, 113.2 pg/mL [10.0-65.0]). Pheochromocytoma screening was negative. A
      provisional diagnosis of MEN 2 was made, but at surgery, a single parathyroid
      adenoma was resected and frozen sections of several lymph nodes revealed
      papillary thyroid carcinoma (PTC). A total thyroidectomy was performed. Final
      histological diagnosis was PTC and parathyroid adenoma with no evidence of MTC.
      Postoperatively, RET mutation testing was positive. The basal calcitonin (CT)
      fell to 25 pg/mL, but peaked at 935 (normal <105) after pentagastrin infusion,
      consistent with occult MTC. After radioiodine ablation, CT decreased further.
      Octreotide scanning was negative. Faced with PHP, a thyroid nodule, and a family
      history of MTC, clinicians tend to diagnose MEN 2. This patient had a single
      parathyroid adenoma and nonmedullary thyroid cancer, which the literature
      actually suggests to be an association more frequent than MEN 2. Yet, there
      remains compelling data in favor of occult MTC, leaving open the possibility of
      an MEN 2 variant with the rare association of PTC.

PMID- 9777748
TI  - Lack of association between polymorphism of the thyrotropin receptor gene and
      Graves' disease in United Kingdom and Hong Kong Chinese patients: case control
      and family-based studies.
AB  - The thyrotropin receptor (TSH-R) gene is a candidate for genetic susceptibility
      to Graves' disease (GD). Previous case control studies investigating allelic
      association of a polymorphism at position 253 (C253 to A253) of the TSH-R gene
      have shown conflicting results. We genotyped two independent case control
      datasets (UK Caucasian and Hong Kong Chinese), for the A253 polymorphism. The
      Transmission Disequilibrium Test was also used in a third family-based dataset
      that included 89 UK Caucasian families (both parents, a GD sibling and an
      unaffected sibling). Genotyping was performed by polymerase chain reaction (PCR)
      amplification of genomic DNA and Tth111 I restriction enzyme digestion. No
      difference in frequencies of the A253 polymorphism between GD (21/204, 10.3%) and
      controls (34/358, 9.5%) was found in the UK Caucasians (chi2 = 0.093; p = NS). A
      similar finding was observed in GD (0/96, 0%) and controls (2/71, 2.8%) in Hong
      Kong Chinese subjects (chi2 = 2.73; p = NS). Results from the 89 UK families
      showed no deviation from the expected transmission frequency of 0.5, from parents
      heterozygous for the A253 allele to either Graves' or unaffected offspring
      (Fisher's exact test p = 0.22) and, therefore, confirmed a lack of evidence of
      linkage disequilibrium between the A253 allele and GD.

PMID- 9777751
TI  - Methimazole-induced aplastic anemia in third exposure: successful treatment with
      recombinant human granulocyte colony-stimulating factor.
AB  - The major adverse reactions of antithyroid drugs are hematologic; aplastic anemia
      (AA) is one of the rarest and most severe complications. Use of recombinant human
      hemopoietic colony-stimulating factor was reported to be of benefit in patients
      who developed agranulocytosis, although there is still some doubt regarding the
      efficacy in AA. We present a case of a 58-year-old female patient with Graves'
      disease who developed AA in the third exposure to methimazole (MMI). The
      withdrawal of MMI and early treatment with 5 microg/kg per day recombinant human
      granulocyte colony-stimulating factor (G-CSF) for 9 days, allowed a favorable
      recovery of peripheral blood cell count. We conclude that the use of hemopoietic
      colony stimulating factors might be a suitable means to achieve the correction of
      severe thionamide-induced hematologic adverse reactions.

PMID- 9777750
TI  - Cerebral venous sinus thrombosis: a late sequel of invasive fibrous thyroiditis.
AB  - Riedel's invasive fibrous thyroiditis (IFT) is a rare disease of unknown etiology
      characterized by a dense fibrosis involving the thyroid gland and its surrounding
      tissues. Clinically, patients present with a stony hard goiter frequently
      associated with compressive symptoms. Involvement of the surrounding neck
      structures by IFT can lead to various clinical sequelae. We report the case of a
      55-year-old woman with known IFT who developed thrombosis in the right internal
      jugular vein that progressed to the right sigmoid, transverse, and superior
      sagittal sinuses. IFT could have predisposed to cerebral venous sinus thrombosis
      by causing venous stasis, vascular damage and possibly a hypercoagulable state.
      To our knowledge, this is the first report of cerebral venous sinus thrombosis
      that developed as a complication of IFT.

PMID- 9777752
TI  - Intrapartum labetalol for the treatment of maternal and fetal thyrotoxicosis.
AB  - Maternal thyrotoxicosis complicates approximately 0.2% of pregnancies.
      Simultaneous occurrence of maternal and fetal thyrotoxicosis during labor is
      rare, and control of maternal tachycardia and hypertension, as well as fetal
      manifestations of thyrotoxicosis, are cornerstones of management. An 18-year-old
      nulliparous female at 33 weeks gestational age presented in labor with
      thyrotoxicosis. Fetal tachycardia was present as well. Labetalol therapy resulted
      in a decrease in maternal pulse and blood pressure, and resolution of fetal
      tachycardia. Vaginal delivery occurred. Subsequent evaluation demonstrated
      neonatal thyrotoxicosis and high maternal titers of thyroid-stimulating
      immunoglobulin. In conclusion, labetalol was beneficial in the treatment of
      maternal and fetal thyrotoxicosis during labor.

PMID- 9777754
TI  - Subclinical thyroid disease in the elderly.
AB  - The development of sensitive assays for thyrotropin (TSH) has led to the
      discovery that many older patients have abnormal TSH levels without other
      alterations in serum thyroid hormone levels, conditions termed subclinical
      hypothyroidism (isolated elevation of TSH levels) and subclinical hyperthyroidism
      (isolated suppression of TSH levels). Subclinical hypothyroidism occurs in 5% to
      10% of elderly subjects, and is especially prevalent in elderly women.
      Subclinical hyperthyroidism is less common, affecting less than 2% of the elderly
      population. The causes of subclinical thyroid disease in the elderly are similar
      to those of thyroid disease in the general population, although medications and
      iodine-containing compounds may play an increased role. Potential risks of
      subclinical hypothyroidism in the elderly include progression to overt
      hypothyroidism, cardiovascular effects, hyperlipidemia, and neurological and
      neuropsychiatric effects. Potential risks of subclinical hyperthyroidism in the
      elderly include progression to overt hyperthyroidism, cardiovascular effects
      (especially atrial fibrillation), and osteoporosis. Decisions to treat elderly
      subjects with subclinical thyroid disease should be based on a careful assessment
      of these risks in the individual patient.

PMID- 9777753
TI  - The effect of recombinant human thyrotropin (rhTSH) on thyroid function in mice
      and rats.
AB  - The vast majority of studies to determine the biological activity of recombinant
      human thyrotropin (rhTSH) have been carried out in the mouse. We have recently
      reported that 0.1 mg of rhTSH IM (one-ninth the dose given in thyroid cancer
      patients) given to normal subjects elicits a brisk rise in serum thyroxine (T4),
      triiodothyronine (T3), and thyroglobulin (Tg) concentrations. In contrast, in
      initial studies in the rat, a low dose of rhTSH failed to increase serum T4 or T3
      concentrations. The present study was, therefore, carried out to determine the
      biological activity of rhTSH in euthyroid and in T3-treated, TSH-suppressed rats
      and mice. Doses of rhTSH based on body weight were used and resulted in similar
      serum human thyrotropin (hTSH) concentrations in the two species. Euthyroid and
      TSH-suppressed mice responded briskly to rhTSH administration. In contrast, serum
      T4 did not increase after rhTSH administration in euthyroid rats. In TSH
      suppressed rats, the increase in serum T4 was similar to that observed in TSH
      suppressed mice. These observations suggest that rhTSH more readily displaces
      endogenous TSH from the mouse than from the rat thyroid TSH receptor, because
      equal responses were observed when endogenous TSH was suppressed.

PMID- 9777755
TI  - "Spot 14" protein: a metabolic integrator in normal and neoplastic cells.
AB  - "Spot 14" (S14) was originally identified as a mRNA from rat liver that responded
      rapidly to thyroid hormone, and has now been shown to play a key role in the
      tissue-specific regulation of lipid metabolism. In addition to its responsiveness
      to thyroid hormone, S14 gene transcription is controlled by dietary substrates,
      such as glucose and polyunsaturated fatty acids, and by fuel-related hormones
      including insulin and glucagon. The S14 protein forms homodimers via a carboxyl
      terminal "zipper" domain. The protein is located primarily in the cell nucleus,
      and its expression in liver is limited to the perivenous portion of the hepatic
      lobule, the site of fatty acid synthesis. S14 protein is critical for the
      induction of key enzymes involved in the switching of hepatic metabolism from the
      fasted to the fed state. S14 antisense oligonucleotides inhibit both the
      intracellular production of lipids and their export as very low-density
      lipoprotein (VLDL) particles. S14 acts at the level of transcription to regulate
      expression of genes encoding key metabolic enzymes, including those required for
      long-chain fatty acid synthesis. The human S14 gene is located at 11q13.5, a
      region that is amplified in a subset of aggressive breast cancers. S14 mRNA is
      expressed in most breast cancer-derived cell lines, and the protein is found in
      the nuclei of two thirds of human breast cancer specimens, but not in normal
      nonlactating mammary glands. S14 expression in breast tumors is highly concordant
      with overabundance of a key lipogenic enzyme. This indicates the association of
      S14 with enhanced tumor lipogenesis, an established marker of poor prognosis. In
      addition to the utility of S14 as a model system for elucidation of the mechanism
      of thyroid hormone action, studies of its regulation and function have provided
      insights into tissue-specific metabolic control by hormones and dietary
      substrates in both normal and neoplastic tissues.

PMID- 9777756
TI  - Effects of environmental synthetic chemicals on thyroid function.
AB  - Synthetic chemicals are released into the environment by design (pesticides) or
      as a result of industrial activity. It is well known that natural environmental
      chemicals can cause goiter or thyroid imbalance. However, the effects of
      synthetic chemicals on thyroid function have received little attention, and there
      is much controversy over their potential clinical impact, because few studies
      have been conducted in humans. This article reviews the literature on possible
      thyroid disruption in wildlife, humans, and experimental animals and focuses on
      the most studied chemicals: the pesticides DDT, amitrole, and the thiocarbamate
      family, including ethylenethiourea, and the industrial chemicals polyhalogenated
      hydrocarbons, phenol derivatives, and phthalates. Wildlife observations in
      polluted areas clearly demonstrate a significant incidence of goiter and/or
      thyroid imbalance in several species. Experimental evidence in rodents, fish, and
      primates confirms the potentiality for thyroid disruption of several chemicals
      and illustrates the mechanisms involved. In adult humans, however, exposure to
      background levels of chemicals does not seem to have a significant negative
      effect on thyroid function, while exposure at higher levels, occupational or
      accidental, may produce mild thyroid changes. The impact of transgenerational,
      background exposure in utero on fetal neurodevelopment and later childhood
      cognitive function is now under scrutiny. There are several studies linking a
      lack of optimal neurological function in infants and children with high
      background levels of exposure to polychlorinated biphenyls (PCBs), dioxins,
      and/or co-contaminants, but it is unclear if the effects are caused by thyroid
      disruption in utero or direct neurotoxicity.

PMID- 9777757
TI  - On the prevalence of familial nonmedullary thyroid cancer.

PMID- 9777758
TI  - Thyroid hyperfunction during pregnancy.
AB  - The present report focuses on the two main causes of hyperthyroidism observed in
      the pregnant state: Graves' disease (GD) and gestational transient
      thyrotoxicosis. Together, the prevalence of hyperthyroidism may represent 3% to
      4% of all pregnancies, and therefore constitutes an important clinical issue.
      Concerning GD, the variable presentations of the disease (women under treatment,
      in remission, or considered cured) and specific alterations occurring in
      pregnancy are discussed: changes in thyrotropin (TSH) receptor antibody titers,
      the risk of fetal and neonatal thyrotoxicosis, the outcome of pregnancy in
      relation to the control of hyperthyroidism, and the treatment of active GD during
      and after pregnancy with antithyroid drugs. Gestational transient thyrotoxicosis
      is associated with a direct stimulation of the maternal thyroid gland by human
      chorionic gonadotropin (hCG), and has been shown to be directly related to both
      the amplitude and duration of peak hCG values. The syndrome is usually transient,
      observed at the end of the first trimester, and is frequently associated with
      emesis. Finally, we propose a global strategy for the systematic screening of
      hyperthyroidism during pregnancy, based on an algorithm that allows for the
      diagnosis of both autoimmune and nonautoimmune forms of hyperthyroidism in the
      pregnant state.

PMID- 9777759
TI  - Cutaneous deposition diseases. Part II.
AB  - Part II of the cutaneous deposition disorders focuses on cutaneous calcification
      and ossification, alkaptonuria and ochronosis, and gout. These disorders have in
      common the deposition of materials in the dermis or subcutis and often involve
      metabolic defects in hormonal and enzymatic regulation. The pathogenesis,
      clinical findings, and treatment of these diseases are discussed. Both the
      histologic and ultrastructural findings are reviewed.

PMID- 9777760
TI  - A side-by-side comparison of carbon dioxide resurfacing lasers for the treatment
      of rhytides.
AB  - BACKGROUND: The use of cutaneous resurfacing lasers to treat rhytides is widely
      accepted. Several carbon dioxide lasers, many using fundamentally different
      technologies, are available. OBJECTIVE: The purpose of this study was to compare
      the results obtained and side effects after treating rhytides with 3 different
      carbon dioxide resurfacing lasers. METHODS: We performed a randomized, blinded,
      prospective study wherein 16 subjects had either periorbital or perioral rhytides
      resurfaced with 1 of 3 carbon dioxide lasers on either side of the face. RESULTS:
      We were unable to demonstrate any significant differences in improvement in
      rhytides, patient satisfaction, posttreatment erythema, or other side effects.
      CONCLUSION: Our results suggest that operator technique and patient selection are
      more important factors than laser type with respect to outcome.

PMID- 9777762
TI  - Onychomatricoma: clinical and histopathologic findings in 12 cases.
AB  - BACKGROUND: Onychomatricoma is a nail matrix tumor that has been well
      characterized clinically but not histologically. OBJECTIVE: The purpose of this
      study was to establish histologic criteria for the diagnosis of onychomatricoma
      to differentiate it from other fibroepithelial tumors of the nail matrix.
      METHODS: We observed 12 cases and were able to examine 4 of these excised
      specimens, including the attached nail plate. In 8 patients, avulsion of the nail
      was performed before excision of the tumor so that the nail plate was examined
      separately from the tumor. RESULTS: Onychomatricoma is a fibroepithelial tumor
      consisting of 2 anatomic zones. The proximal zone is located beneath the proximal
      nail fold with a proximal border starting at the root of the nail and distal
      border corresponding to the cuticle. It is characterized by deep epithelial
      invaginations filled with a thick V-shaped keratogenous zone, a thickened nail
      plate without cavitation but with an undulating inferior border ending in ungual
      spurs, and a fibrillary stroma clearly demarcated from the undersurface. The
      distal zone corresponds to the lunula and is characterized by multiple "glove
      finger" digitations lined with matrix epithelium and oriented around antero
      oblique connective tissue axes; perforation of the nail plate by multiple
      cavities that, generally at the distal edge of the lunula, lose their epithelial
      digitations and become filled with serous fluid; the connective-tissue stoma of
      the digitations extends deeply into the dermis and is not demarcated form healthy
      tissue. CONCLUSION: On the basis of the mentioned characteristics, we have been
      able to define onychomatricoma histologically. In addition, we have identified an
      unusual clinical form of onychomatricoma that has the appearance of a cutaneous
      horn and is situated at the junction of the undersurface of the proximal nailfold
      and the lateral nailfold.

PMID- 9777761
TI  - Immunophenotyping and T-cell receptor gamma gene rearrangement analysis as an
      adjunct to the histopathologic diagnosis of mycosis fungoides.
AB  - BACKGROUND: The histopathologic diagnosis of mycosis fungoides (MF) may be
      difficult. OBJECTIVE: Our purpose was to evaluate the role of immunophenotyping
      and T-cell receptor (TCR) gene rearrangement studies as an adjunct to the
      histopathologic diagnosis of MF. METHODS: Immunohistochemical studies with
      antibodies to CD4, CD5, CD7, and CD8 and TCR gamma gene rearrangement analysis
      with a polymerase chain reaction were performed on fresh-frozen material of
      patients with "classic" histology of MF, "inconclusive" histology, and benign
      inflammatory dermatoses. RESULTS: Clonal TCR gamma gene rearrangements were found
      in 11 of 16 (69%) of classic MF cases, in 3 of 19 (16%) of inconclusive cases,
      and in none of the 12 inflammatory dermatoses cases (P < .05 and P < .001,
      respectively). Only the mean CD7 counts were statistically significantly
      different between these 3 groups (MF < inconclusive < inflammatory). CONCLUSION:
      Inconclusive histology is probably a heterogeneous group in which CD7 counts and
      TCR gamma gene rearrangement studies might help to differentiate the MF cases
      from the benign cases.

PMID- 9777763
TI  - Cockayne syndrome without typical clinical manifestations including neurologic
      abnormalities.
AB  - Although patients with mild symptoms of atypical Cockayne syndrome (CS) have been
      described, there has not been a report of a patient with CS whose only clinical
      manifestation was cutaneous photosensitivity. Cells from patients with CS show UV
      sensitivity, reduced recovery of RNA synthesis, but normal UV-induced unscheduled
      DNA synthesis. On the other hand, the patients with UV-sensitive syndrome have
      only cutaneous photosensitivity and skin freckles, whereas those cells respond to
      UV radiation in a similar fashion to the CS cells. We describe a patient with CS
      who showed only photosensitivity without typical clinical manifestations of CS,
      but his cells showed UV sensitivity, reduced recovery of RNA synthesis, and
      normal unscheduled DNA synthesis after UV radiation similar to CS cells.
      Furthermore, the patient was assigned to complementation group B of CS on the
      basis of the results of complementation analysis. The present report suggests
      that CS has a wider spectrum than that considered previously.

PMID- 9777764
TI  - Cutaneous melanoma: patient surveillance and tumor progression.
AB  - BACKGROUND: The goal of surveillance examinations (SVE) in patients at high risk
      for cutaneous melanoma (CM) is to diagnose premetastatic tumors. OBJECTIVE: We
      attempted to determine whether SVE before CM diagnosis influences the
      histopathologic features of tumor progression. METHODS: A retrospective review
      was conducted of consecutive patients who presented with an intact primary CM
      during a 36 month period (1991 to 1994) in a university dermatology ambulatory
      setting. RESULTS: Thirty-nine intact CMs were diagnosed in 34 patients. Compared
      with 23 CMs in as many patients presenting at the first encounter, 16 CMs
      diagnosed in 11 patients during SVE had a smaller mean tumor diameter (P = .007)
      and tumor thickness (P = .002) and were more likely anatomic level I or II (P =
      .003) with microscopic thickness less than 0.76 mm (P = .01) and less than 0.50
      mm (P = .002). CONCLUSION: Primary CMs are more likely to be smaller and thinner
      when diagnosed during SVE than at first encounter, features that are likely to
      have a positive impact on CM mortality.

PMID- 9777766
TI  - Tazarotene 0.1% gel plus corticosteroid cream in the treatment of plaque
      psoriasis.
AB  - BACKGROUND: Topical corticosteroids are often used in the treatment of psoriasis,
      but long-term use may be associated with serious adverse events such as
      tachyphylaxis or atrophy of the skin. Tazarotene, a new topical retinoid, has
      demonstrated significant clinical benefits but can cause mild to moderate local
      irritation. OBJECTIVE: We evaluate whether a combination treatment of topical
      tazarotene and a topical corticosteroid would increase efficacy while reducing
      the incidence of local adverse events associated with a topical retinoid.
      METHODS: Three hundred patients enrolled in an investigator-masked study were
      randomly assigned to 1 of 4 treatment groups: tazarotene 0.1% gel in combination
      with placebo cream, or with a low-, mid-, or high-potency corticosteroid cream,
      for 12 weeks of treatment and a posttreatment follow-up at week 16. RESULTS:
      Tazarotene 0.1% gel in combination with a mid- or high-potency corticosteroid,
      when compared with tazarotene plus placebo cream, achieved significantly greater
      reductions in scaling, erythema, and overall lesional severity, and a decreased
      incidence of adverse events. CONCLUSION: All tazarotene combinations (including
      tazarotene plus placebo) were highly effective in rapidly reducing the severity
      of psoriasis. Combining tazarotene with a topical corticosteroid increased
      efficacy while reducing the incidence of local adverse events.

PMID- 9777765
TI  - Finasteride in the treatment of men with androgenetic alopecia. Finasteride Male
      Pattern Hair Loss Study Group.
AB  - BACKGROUND: Androgenetic alopecia (male pattern hair loss) is caused by androgen
      dependent miniaturization of scalp hair follicles, with scalp dihydrotestosterone
      (DHT) implicated as a contributing cause. Finasteride, an inhibitor of type II
      5alpha-reductase, decreases serum and scalp DHT by inhibiting conversion of
      testosterone to DHT. OBJECTIVE: Our purpose was to determine whether finasteride
      treatment leads to clinical improvement in men with male pattern hair loss.
      METHODS: In two 1-year trials, 1553 men (18 to 41 years of age) with male pattern
      hair loss received oral finasteride 1 mg/d or placebo, and 1215 men continued in
      blinded extension studies for a second year. Efficacy was evaluated by scalp hair
      counts, patient and investigator assessments, and review of photographs by an
      expert panel. RESULTS: Finasteride treatment improved scalp hair by all
      evaluation techniques at 1 and 2 years (P < .001 vs placebo, all comparisons).
      Clinically significant increases in hair count (baseline = 876 hairs), measured
      in a 1-inch diameter circular area (5.1 cm2) of balding vertex scalp, were
      observed with finasteride treatment (107 and 138 hairs vs placebo at 1 and 2
      years, respectively; P < .001). Treatment with placebo resulted in progressive
      hair loss. Patients' self-assessment demonstrated that finasteride treatment
      slowed hair loss, increased hair growth, and improved appearance of hair. These
      improvements were corroborated by investigator assessments and assessments of
      photographs. Adverse effects were minimal. CONCLUSION: In men with male pattern
      hair loss, finasteride 1 mg/d slowed the progression of hair loss and increased
      hair growth in clinical trials over 2 years.

PMID- 9777767
TI  - Pulse methylprednisolone therapy for severe alopecia areata: an open prospective
      study of 45 patients.
AB  - BACKGROUND: Oral corticosteroids may be effective in the treatment of severe
      alopecia areata (AA), but the side effects of prolonged therapy limit their use.
      The benefit of a single intravenous pulse of methylprednisolone has not been
      evaluated in patients with ongoing hair loss of less than 12 months' duration.
      OBJECTIVE: Our purpose was to determine the effectiveness of an intravenous pulse
      of methylprednisolone at 1, 3, 6, and 12 months in patients with active severe AA
      of less than 12 months' duration. METHODS: Forty-five patients were included in
      this open study. All had rapid and extensive hair loss for less than 1 year
      (first occurrence or relapse), with the bald area exceeding 30% of the scalp.
      There were 20 multifocal, 10 ophiasic, 9 universalis, and 6 totalis cases.
      Intravenous methylprednisolone, 250 mg, was administered twice a day on 3
      successive days. Follow-up for at least 12 months (up to 29 months) was
      performed. The percentage of pretreatment bald area covered by hair regrowth at
      1,3,6, and 12 months was measured. RESULTS: No major side effects were observed.
      Patients with multifocal AA (n = 20) showed the best response rate, with 9, 12,
      13, and 12 showing 100% or 50% to 100% regrowth at 1, 3, 6, and 12 months,
      respectively. Relapse occurred at 3 months in 1 patient, at 6 months in 2, and at
      12 months in 4. A second pulse was tried in 2 patients with relapse with 100%
      regrowth that was stable at 12 and 28 months. In patients with ophiasic AA (n =
      10), no total regrowth was observed; 6 had no response, 4 showed 20% to 70%
      regrowth at 1 month with relapse at 3 and 6 months. A second series of pulses was
      given to the 4 initial responders 3 to 13 months after the first series; the
      response rate to this second treatment was better than the first. In patients
      with universalis and totalis AA (n = 15), no total regrowth was observed
      initially; 8 patients had no response, and 3 showed 50% to 90% regrowth at I
      month, with subsequent improvement at 3 and 6 months. In 4 patients who did not
      show an initial response, a significant (90% to 100%) delayed regrowth was
      observed between 9 and 16 months after the pulse therapy. CONCLUSION: A single
      series of intravenous pulse of methylprednisolone appears to be well tolerated
      and effective in patients with rapidly progressing extensive multifocal AA, but
      not those with ophiasic and universalis AA.

PMID- 9777768
TI  - Lymphatic mapping and sentinel node biopsy in the management of high-risk
      melanoma.
AB  - We review sentinel lymph node biopsy in patients with high-risk melanoma. This
      method of selective lymphadenectomy provides valuable staging information about
      the regional lymphatics without the need of prophylactic complete lymph node
      dissection. Only patients with micrometastases are candidates for complete lymph
      node dissection. This avoids, in nearly 85% of patients, the morbidity of the
      more extensive procedure. In addition, sentinel lymph node-positive patients may
      qualify for adjuvant therapy protocols. Whether this surgical approach ultimately
      results in a survival advantage awaits the results of a National Cancer Institute
      sponsored national multicenter trial.

PMID- 9777769
TI  - Uses of vitamins A, C, and E and related compounds in dermatology: a review.
AB  - Vitamins have been increasingly used as prophylactic and therapeutic agents in
      the management of skin disorders. The current literature is replete with studies
      that promote the potential benefits of these compounds and attempt to elucidate
      their mechanisms of action. We review the literature and discuss the roles,
      safety, and efficacy of vitamins A, C, and E and related compounds in cutaneous
      health and disease.

PMID- 9777770
TI  - Useful plants of dermatology. V. Capsicum and capsaicin.

PMID- 9777771
TI  - Surgical pearl: nail splinting by flexible tube--a new noninvasive treatment for
      ingrown toenails.

PMID- 9777772
TI  - Linear pustular psoriasis that developed in a patient with generalized pustular
      psoriasis.

PMID- 9777773
TI  - Cutaneous metastasis presenting as facial lymphedema.

PMID- 9777775
TI  - An improved method of studying fingernail morphometry: application to the early
      detection of fingernail clubbing.

PMID- 9777774
TI  - Prenatal findings in membranous aplasia cutis.

PMID- 9777776
TI  - Estrogen-sensitive cutaneous polyarteritis nodosa: response to tamoxifen.

PMID- 9777777
TI  - Sparing of tuberculoid leprosy patch in a patient with dapsone hypersensitivity
      syndrome.

PMID- 9777778
TI  - Efficacy of tacrolimus (FK 506) in idiopathic treatment-resistant pyoderma
      gangrenosum.

PMID- 9777780
TI  - Paraneoplastic dermatomyositis presenting as erythroderma.

PMID- 9777779
TI  - Mycobacterium fortuitum panniculitis in a steroid-dependent asthmatic patient.

PMID- 9777781
TI  - Onychomycosis in a 2-year-old child successfully treated with oral terbinafine.

PMID- 9777782
TI  - Unilateral hyperkeratosis lenticularis perstans (Flegel's disease).

PMID- 9777783
TI  - Medical missions and dermatology.

PMID- 9777784
TI  - Acne keloidalis is lichen simplex chronicus with fibrotic keloidal scarring.

PMID- 9777785
TI  - Purpura in infants and children.

PMID- 9777786
TI  - Guidelines of care: hemangiomas of infancy.

PMID- 9777787
TI  - Photosensitivity of the American Indian: terminology and historical aspects.

PMID- 9777788
TI  - The mechanism of "suction".

PMID- 9777789
TI  - Rational design of receptor-selective retinoids.
AB  - Orally administered retinoids can be associated with significant adverse effects
      because of high systemic exposure and a lack of receptor selectivity. Targeting
      the diseased tissue and improving the selectivity of the retinoid-receptor
      interaction to activate only those discrete pathways required for efficacy may
      minimize adverse effects. First- and second-generation retinoids contain several
      alternating single and double bonds that confer great conformational flexibility,
      allowing the molecules to adopt a variety of shapes and creating the potential to
      interact with multiple receptors. We hypothesized that, by designing a more rigid
      conformational structure, the receptor selectivity of retinoids could be improved
      and their therapeutic index enhanced. This strategy has resulted in the
      development of tazarotene. The receptor selectivity of tazarotene, together with
      its topical delivery, ensures a targeted action on psoriatic keratinocytes.

PMID- 9777790
TI  - The pathogenesis of psoriasis and the mechanism of action of tazarotene.
AB  - The 3 major features of psoriasis--abnormal differentiation of keratinocytes,
      hyperproliferation of keratinocytes, and infiltration of inflammatory components
      into the skin--can be quantified by measuring levels of certain biochemical
      markers. Psoriasis is associated with upregulation or downregulation of several
      of these markers. Tazarotene helps to normalize the levels of the markers,
      thereby bringing about clinical improvement.

PMID- 9777791
TI  - Pharmacokinetics and safety review of tazarotene.
AB  - The safety profile of tazarotene is superior to that of orally administered
      retinoids. The limited percutaneous penetration of tazarotene limits its systemic
      absorption and this, combined with its rapid metabolism in the skin and the
      plasma to the more water-soluble active metabolite, tazarotenic acid, helps
      prevent accumulation of the drug in fat containing tissues. Urinary and fecal
      elimination are virtually complete within 2 to 3 days and 7 days after dosing,
      respectively. Tazarotene also exhibits no indication of mutagenicity,
      carcinogenicity, phototoxic potential, photoallergic potential, or contact
      sensitization.

PMID- 9777792
TI  - Tazarotene in combination with topical corticosteroids.
AB  - The use of a topical corticosteroid in combination with tazarotene has theoretic
      appeal because each drug has a different mechanism of action, and it is therefore
      likely that combination therapy will offer additive or synergistic effects. For
      example, the steroid may promote a rapid initial response together with
      minimization of erythema during the treatment period, and tazarotene may prolong
      the duration of the therapeutic effect and lower the probability of relapse. The
      results of a large, controlled clinical trial in which corticosteroids of various
      potencies were added to tazarotene therapy showed that tazarotene plus a medium-
      or high potency corticosteroid produced greater and more rapid efficacy, and
      superior tolerability, than tazarotene plus placebo cream.

PMID- 9777793
TI  - Tazarotene in combination with phototherapy.
AB  - Despite the vast array of available therapies for treating psoriasis, there
      remains a need for safer, more effective treatments. Topical tazarotene has been
      shown to be effective in treating mild-to-moderate psoriasis without causing the
      adverse effects, such as mucocutaneous toxicity, hyperostosis, and elevation in
      serum lipids, often associated with orally administered retinoids. A 2-week
      pretreatment with tazarotene 0.1% gel once daily, followed by tazarotene plus UVB
      therapy (tazarotene-UVB) 3 times per week for 10 weeks, was more effective than
      UVB therapy alone or in combination with vehicle gel in reducing plaque
      elevation, scaling, and erythema. The tazarotene-UVB treatment was well
      tolerated, and no phototoxicity was observed. Treatment success, defined as a
      moderate response or better in psoriatic lesions (ie, > or = 50% improvement in
      psoriatic lesions compared with baseline), was achieved within 32 days with the
      tazarotene-UVB treatment, compared with 67 days with UVB alone or UVB plus
      vehicle gel.

PMID- 9777794
TI  - Future trends: a new generation of retinoids.
AB  - The existence of several different types of retinoid receptors, response
      elements, and cofactors means that retinoid physiology is mediated by multiple
      discrete pathways and is highly complex. As a result, non-selective retinoids
      have a multitude of physiologic effects and are usually associated with toxicity
      problems that limit their therapeutic usefulness. In contrast, because receptor
      selective retinoids have a more focused and targeted action, they are likely to
      have a better therapeutic index. Tazarotene is the first of a new generation of
      receptor-selective retinoids. Its actions are targeted on 2 retinoic acid
      receptors (RARs), RAR-beta and RAR-gamma. Current retinoid research is leading to
      the development not only of many more novel receptor-selective retinoids but also
      of novel types of function-selective retinoids such as RAR inverse agonists and
      RAR antagonists. These retinoids are expected to be of clinical benefit not only
      in dermatology but also in oncology, diabetes, and diseases associated with the
      human papilloma virus.

PMID- 9777796
TI  - Can light coming through the skin reset the clock?

PMID- 9777795
TI  - Blind people often sleep poorly; research shines light on therapy.

PMID- 9777797
TI  - Study: treatment works for substance abusers.

PMID- 9777798
TI  - Safe America plans to make injuries no accident.

PMID- 9777800
TI  - From the Centers for Disease Control and Prevention. Youth agricultural work
      related injuries treated in emergency departments--United States, October 1995
      September 1997.

PMID- 9777799
TI  - From the Food and Drug Administration.

PMID- 9777801
TI  - From the Centers for Disease Control and Prevention. Haemophilus influenzae
      invasive disease among children aged <5 years--California, 1990-1996.

PMID- 9777802
TI  - From the Centers for Disease Control and Prevention. Imported dengue--United
      States, 1996.

PMID- 9777803
TI  - Saving the vision of children with juvenile rheumatoid arthritis-associated
      uveitis.

PMID- 9777804
TI  - A piece of my mind. On being human.

PMID- 9777805
TI  - Prominence of patients' insurance status in clinical crossroads.

PMID- 9777806
TI  - The future of Blue Cross and Blue Shield.

PMID- 9777807
TI  - Alcohol consumption and breast cancer risk.

PMID- 9777808
TI  - Declines in population sex ratios at birth.

PMID- 9777809
TI  - Declines in population sex ratios at birth.

PMID- 9777810
TI  - Declines in population sex ratios at birth.

PMID- 9777811
TI  - Industry affiliations and scientific conclusions.

PMID- 9777812
TI  - Industry affiliations and scientific conclusions.

PMID- 9777813
TI  - Impact of a large-scale immunization initiative in the Special Supplemental
      Nutrition Program for Women, Infants, and Children (WIC)
AB  - CONTEXT: Inner-city immunization rates have lagged behind those in other areas of
      the country. OBJECTIVE: To evaluate the impact of an initiative linking
      immunization with distribution of food vouchers in the inner city. DESIGN:
      Retrospective analysis of immunization data gathered in 1996 and 1997. SETTING:
      Nineteen Special Supplemental Nutrition Program for Women, Infants, and Children
      (WIC) sites serving 30% of the Chicago, III, birth cohort. PARTICIPANTS: A total
      of 16581 children 24 months old or younger. INTERVENTIONS: Voucher incentives
      (varying frequency of food voucher issuance based on immunization status) and
      assessment of immunization status and referral to immunization provider. MAIN
      OUTCOME MEASURES: Age-appropriate immunization rates and WIC enrollment rates.
      RESULTS: During the 15-month period of evaluation, immunization rates increased
      from 56% to 89% at sites performing voucher incentives. The proportion of
      children needing voucher incentives declined from 51% to 12%. Sites performing
      assessment and referral, but not providing voucher incentives, showed no evidence
      of improvement in immunization coverage. No difference was observed in enrollment
      rates between sites performing voucher incentives and those that did not.
      CONCLUSION: Applied in a large-scale, programmatic fashion, voucher incentives in
      WIC can rapidly increase and sustain high childhood immunization rates in an
      inner-city population.

PMID- 9777814
TI  - Barriers to cadaveric renal transplantation among blacks, women, and the poor.
AB  - CONTEXT: Cadaveric renal transplantation rates differ greatly by race, sex, and
      income. Previous efforts to lessen these differences have focused on the
      transplant waiting list. However, the transplantation process involves a series
      of steps related to medical suitability, interest in transplantation,
      pretransplant workup, and movement up a waiting list to eventual transplantation.
      OBJECTIVE: To determine the relative importance of each step in explaining
      differences in cadaveric renal transplantation rates. DESIGN: Prospective cohort
      study. SETTING AND PATIENTS: A total of 7125 patients beginning long-term
      dialysis between January 1993 and December 1996 in Indiana, Kentucky, and Ohio.
      MAIN OUTCOME MEASURES: Completion of 4 separate steps during each patient-year of
      follow-up: (A) being medically suitable and possibly interested in
      transplantation; (B) being definitely interested in transplantation; (C)
      completing the pretransplant workup; and (D) moving up a waiting list and
      receiving a transplant. RESULTS: Compared with whites, blacks were less likely to
      complete steps B (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.61
      0.76), C (OR, 0.56; 95% CI, 0.48-0.65), and D (OR, 0.50; 95% CI, 0.40-0.62) after
      adjustment for age, sex, cause of renal failure, years receiving dialysis, and
      median income of patient ZIP code. Compared with men, women were less likely to
      complete each of the 4 steps, with ORs of 0.90, 0.89, 0.80, and 0.82,
      respectively. Poor individuals were less likely than wealthy individuals to
      complete steps A, B, and C, with ORs of 0.67, 0.78, and 0.77, respectively.
      CONCLUSIONS: Barriers at several steps are responsible for sociodemographic
      differences in access to cadaveric renal transplantation. Efforts to allocate
      kidneys equitably must address each step of the transplant process.

PMID- 9777815
TI  - Center-specific graft and patient survival rates: 1997 United Network for Organ
      Sharing (UNOS) report.
AB  - CONTEXT: Multiple comprehensive, risk-adjusted studies evaluating short-term
      surgical mortality have been reported previously. This report analyzes short-term
      and long-term outcomes, both nationally and at each individual transplant
      program, for all solid organ transplantations performed in the United States.
      OBJECTIVES: To report graft and patient survival rates for all solid organ
      transplantations, both nationally and at each specific transplant program in the
      United States, and to compare the expected survival rate with the actual survival
      rate of each individual program. DESIGN AND SETTING: Multivariate regression
      analysis of donor and recipient factors affecting graft and patient survival of
      all kidney, liver, pancreas, heart, lung, and heart-lung transplants reported to
      the United Network for Organ Sharing from 742 separate transplant programs.
      PATIENTS: A cohort of 97587 solid organ transplantations performed on 92966
      recipients in the United States from January 1988 through April 1994. MAIN
      OUTCOME MEASURES: Short-term and conditional 3-year national and individual
      transplant program graft and patient survival rates overall and from 2 separate
      eras (era 1, January 1988-April 1992; era 2, May 1992-April 1994); comparison of
      actual center-specific performance with risk-adjusted expected performance and
      identification of centers with better-than-expected or worse-than-expected
      survival rates. RESULTS: One-year graft follow-up exceeded 98% and conditional 3
      year follow-up exceeded 91% for all organs. Graft and patient survival improved
      significantly in era 2 compared with era 1 for all cadaver organs except heart,
      which remained the same. One-year cadaveric graft survival ranged from 81.5% for
      heart to 61.9% for heart-lung and 3-year conditional graft survival ranged from
      91.3% for pancreas to 74.7% for lung. The percentage of programs whose actual 1
      year graft survival was not different from or was better than their risk-adjusted
      expected survival ranged from 98.3% for heart-lung to 75.7% for liver. Most
      kidney, liver, and heart programs whose actual survival was significantly less
      than expected performed small numbers (less than the national average) of
      transplantations per year. CONCLUSIONS: Graft and patient survival for solid
      organ transplantations showed improvement over time. Conditional 3-year graft and
      patient survival rates were approximately 90% for all organs except for lung and
      heart-lung. The conditional 3-year survival rates were better than 1-year
      survival rates, indicating the major risk after transplantation occurs in the
      first year. The majority of transplant programs achieved actual survival rates
      not significantly different from their expected survival rates. Center effects
      were most significant within the first year after transplantation and had much
      less influence on long-term survival outcomes.

PMID- 9777816
TI  - Efficacy of risk-reduction counseling to prevent human immunodeficiency virus and
      sexually transmitted diseases: a randomized controlled trial. Project RESPECT
      Study Group.
AB  - CONTEXT: The efficacy of counseling to prevent infection with the human
      immunodeficiency virus (HIV) and other sexually transmitted diseases (STDs) has
      not been definitively shown. OBJECTIVE: To compare the effects of 2 interactive
      HIV/STD counseling interventions with didactic prevention messages typical of
      current practice. DESIGN: Multicenter randomized controlled trial (Project
      RESPECT), with participants assigned to 1 of 3 individual face-to-face
      interventions. SETTING: Five public STD clinics (Baltimore, Md; Denver, Colo;
      Long Beach, Calif; Newark, NJ; and San Francisco, Calif) between July 1993 and
      September 1996. PARTICIPANTS: A total of 5758 heterosexual, HIV-negative patients
      aged 14 years or older who came for STD examinations. INTERVENTIONS: Arm 1
      received enhanced counseling, 4 interactive theory-based sessions. Arm 2 received
      brief counseling, 2 interactive risk-reduction sessions. Arms 3 and 4 each
      received 2 brief didactic messages typical of current care. Arms 1, 2, and 3 were
      actively followed up after enrollment with questionnaires at 3, 6, 9, and 12
      months and STD tests at 6 and 12 months. An intent-to-treat analysis was used to
      compare interventions. MAIN OUTCOME MEASURES: Self-reported condom use and new
      diagnoses of STDs (gonorrhea, chlamydia, syphilis, HIV) defined by laboratory
      tests. RESULTS: At the 3- and 6-month follow-up visits, self-reported 100% condom
      use was higher (P<.05) in both the enhanced counseling and brief counseling arms
      compared with participants in the didactic messages arm. Through the 6-month
      interval, 30% fewer participants had new STDs in both the enhanced counseling
      (7.2%; P= .002) and brief counseling (7.3%; P= .005) arms compared with those in
      the didactic messages arm (10.4%). Through the 12-month study, 20% fewer
      participants in each counseling intervention had new STDs compared with those in
      the didactic messages arm (P = .008). Consistently at each of the 5 study sites,
      STD incidence was lower in the counseling intervention arms than in the didactic
      messages intervention arm. Reduction of STD was similar for men and women and
      greater for adolescents and persons with an STD diagnosed at enrollment.
      CONCLUSIONS: Short counseling interventions using personalized risk reduction
      plans can increase condom use and prevent new STDs. Effective counseling can be
      conducted even in busy public clinics.

PMID- 9777817
TI  - Age-race subgroup compared with renin profile as predictors of blood pressure
      response to antihypertensive therapy. Department of Veterans Affairs Cooperative
      Study Group on Antihypertensive Agents.
AB  - CONTEXT: Renin profiling and age-race subgroup may help select single-drug
      therapy for stage 1 and stage 2 hypertension. OBJECTIVE: To compare the plasma
      renin profiling and age-race subgroup methods as predictors of response to single
      drug therapy in men with stage 1 and 2 hypertension as defined by the Joint
      National Committee on Prevention, Detection, Evaluation and Treatment of High
      Blood Pressure. DESIGN: The Veterans Affairs Cooperative Study on Single-Drug
      Therapy of Hypertension, a randomized controlled trial. SETTING: Fifteen Veterans
      Affairs hypertension centers. PATIENTS: A total of 1105 ambulatory men with entry
      diastolic blood pressure (DBP) of 95 to 109 mm Hg, of whom 1031 had valid plasma
      and urine samples for renin profiling. INTERVENTIONS: Randomization to 1 of 6
      antihypertensive drugs: hydrochlorothiazide, atenolol, captopril, clonidine,
      diltiazem (sustained release), or prazosin. MAIN OUTCOME MEASURE: Treatment
      response as assessed by percentage achieving goal DBP (<90 mm Hg) in response to
      a single drug that corresponded to patients' renin profile vs a single drug that
      corresponded to patients' age-race subgroup. RESULTS: Clonidine and diltiazem had
      consistent response rates regardless of renin profile (76%, 67%, and 80% for low,
      medium, and high renin, respectively, for clonidine and 83%, 82%, and 83%,
      respectively, for diltiazem for patients with baseline DBP of 95-99 mm Hg).
      Hydrochlorothiazide and prazosin were best in low- and medium-renin profiles;
      captopril was best in medium- and high-renin profiles (low-, medium-, and high
      renin response rates were 82%, 78%, and 14%, respectively, for
      hydrochlorothiazide; 88%, 67%, and 40%, respectively, for prazosin; and 51%, 83%,
      and 100%, respectively, for captopril for patients with baseline DBP of 95-99 mm
      Hg). Response rates for patients with baseline DBP of 95 to 99 mm Hg by age-race
      subgroup ranged from 70% for clonidine to 90% for prazosin for younger black men,
      from 50% for captopril to 97% for diltiazem for older black men, from 70% for
      hydrochlorothiazide to 92% for atenolol for younger white men, and from 84% for
      hydrochlorothiazide to 95% for diltiazem for older white men. Patients with a
      correct treatment for their renin profile but incorrect for age-race subgroup had
      a response rate of 58.7%; patients with an incorrect treatment for their renin
      profile but correct for age-race subgroup had a response rate of 63.1% (P = .30).
      After controlling for DBP and interactions with treatment group, age-race
      subgroup (P<.001) significantly predicted response to single-drug therapy,
      whereas renin profile was of borderline significance (P= .05). CONCLUSIONS: In
      these men with stage 1 and stage 2 hypertension, therapeutic responses were
      consistent with baseline renin profile, but age-race subgroup was a better
      predictor of response.

PMID- 9777819
TI  - Reconfiguring child health services in the inner city.

PMID- 9777818
TI  - Prying open the door to the tobacco industry's secrets about nicotine: the
      Minnesota Tobacco Trial.
AB  - In 1994 the state of Minnesota filed suit against the tobacco industry. This
      trial is now history, but its legacy will carry on into the 21st century because
      of the revelations contained in the millions of pages of previously secret
      internal tobacco industry documents made public in the trial. In this article, we
      review representative documents relating to nicotine addiction, low-tar, low
      nicotine cigarettes, and cigarette design and nicotine manipulation in cigarette
      manufacture. These documents reveal that for decades, the industry knew and
      internally acknowledged that nicotine is an addictive drug and cigarettes are the
      ultimate nicotine delivery device; that nicotine addiction can be perpetuated and
      even enhanced through cigarette design alterations and manipulations; and that
      "health-conscious" smokers could be captured by low-tar, low-nicotine products,
      all the while ensuring the marketplace viability of their products. Appreciation
      of tobacco industry strategies over the past decades is essential to formulate an
      appropriate legislative and public policy response. We propose key elements for
      such legislation and urge no legal or financial immunity for the tobacco
      industry.

PMID- 9777821
TI  - Smoke and spirits: the substance abuse dilemma.

PMID- 9777820
TI  - Organ transplantation--barriers, outcomes, and evolving policies.

PMID- 9777823
TI  - Tobacco and alcohol use among 1996 medical school graduates.

PMID- 9777822
TI  - Primary care as harm reduction for injection drug users.

PMID- 9777824
TI  - The international tobacco strategy.

PMID- 9777825
TI  - JAMA patient page: organ and tissue donation.

PMID- 9777826
TI  - A meeting too many.

PMID- 9777827
TI  - Genes and disease expression in hypertrophic cardiomyopathy.

PMID- 9777828
TI  - Malaria vaccines: are seven antigens better than one?

PMID- 9777830
TI  - Trials and tribulations in cervical spondylosis.

PMID- 9777829
TI  - Questionnaire approach to diagnosis in developing countries.

PMID- 9777831
TI  - UK medicine: what are we to do?

PMID- 9777833
TI  - Relation between semen quality and fertility: a population-based study of 430
      first-pregnancy planners.
AB  - BACKGROUND: Semen analysis is part of the routine assessment of infertile
      couples. WHO defines a sperm concentration above 20x10(6) per mL seminal fluid as
      normal. We studied the association between semen quality and the probability of
      conception in a single menstrual cycle in Danish couples with no previous
      reproductive experience. METHODS: In 1992-94, we invited 52,255 trades-union
      members aged 20-35 years, who lived with a partner and had no children to take
      part in the study; 430 couples agreed. The couples discontinued use of
      contraception, and were followed up for six menstrual cycles or until a pregnancy
      was verified within this period. Each man was asked to provide a semen sample at
      enrolment (which was analysed without freezing). Women kept a daily record of
      vaginal bleeding and sexual activity. The association between semen quality and
      likelihood of pregnancy was assessed by logistic regression, adjusted for sexual
      activity and female factors associated with low fertility. RESULTS: There were
      256 (59.5%) pregnancies among the 430 couples: 165 (65.0%) among those with a
      sperm concentration of 40x10(6)/mL or more and 84 (51.2%) among those with lower
      sperm concentrations. The probability of conception increased with increasing
      sperm concentration up to 40x10(6)/mL, but any higher sperm density was not
      associated with additional likelihood of pregnancy. The proportion of sperm with
      normal morphology was strongly related to likelihood of pregnancy independently
      of sperm concentration. Semen volume and motility were of limited value in
      pregnancy prediction. INTERPRETATION: Our study suggests that the current WHO
      guidelines for normal semen quality should be used with caution. Some men with
      sperm counts above the lower limit of the normal range defined by WHO may in fact
      be subfertile.

PMID- 9777832
TI  - Prevalence of atrial fibrillation and eligibility for anticoagulants in the
      community.
AB  - BACKGROUND: Anticoagulants are effective in the prevention of stroke in atrial
      fibrillation and flutter (AF). We aimed to find out the prevalence of AF in the
      UK and to estimate the proportion of patients with AF who might benefit from
      anticoagulation. METHODS: We screened with electrocardiography a random sample of
      4843 people from the community aged 65 years and older for AF. Participants with
      AF had further investigations to identify risk factors for stroke and
      contraindications to anticoagulants. We used three sets of criteria to assess
      risk and eligibility for anticoagulation. FINDINGS: 228 (4.7%) participants had
      AF. According to analyses derived from risk stratifications based on the Stroke
      Prevention in Atrial Fibrillation (SPAF) study 61% of these patients would have
      benefited from anticoagulation, 49% according to pooled analysis of trial
      results, and 41% according to the inclusion criteria for the SPAF 3 study.
      Anticoagulants were used by 1114 (23%) of all patients and were least used among
      elderly women, who may be the most likely to benefit. Echocardiography would be
      useful to assess the need for anticoagulation only in patients younger than 75
      years with no contraindications to treatment and no clinical risk factors for
      stroke. INTERPRETATION: Anticoagulants seem to be underused and misdirected in
      treatment of AF, according to various criteria. Efforts to promote and support
      wider and more appropriate use of anticoagulants would seem to be justified, and
      should decrease the incidence of stroke amongst elderly patients.

PMID- 9777834
TI  - Administration of desmopressin in brain-dead donors and renal function in kidney
      recipients.
AB  - BACKGROUND: Diabetes insipidus is common among brain-dead donors and may lead to
      decreased graft function. The use of desmopressin to limit the consequences of
      diabetes insipidus is controversial. We assessed the effects of desmopressin
      administered to brain-dead donors on early and long-term graft function in kidney
      recipients. METHODS: In a randomised controlled study, 97 brain-dead donors
      received desmopressin as 1 microg bolus every 2 h when diuresis was more than 300
      mL/h (desmopressin group n=49) or no desmopressin (control group n=48). In 175
      kidney recipients (controls n=89, desmopressin group n=86) we measured serum
      concentrations of creatinine and haemodialysis requirements to assess early renal
      function in the first 15 days after transplantation. We assessed long-term
      results of transplantation (median time 45 months) for a homogeneous subgroup of
      95 recipients (48 in the desmopressin group). FINDINGS: We found no significant
      differences between the two groups of brain-dead donors, except for final
      diuresis, which was lower in the desmopressin group than among controls.
      Haemodialysis requirement in controls and the desmopressin group (20 vs 23%,
      p=0.63) and serum creatinine concentrations (decrease from 903 micromol/L to 206
      micromol/L vs 814 micromol/L to 193 micromol/L, p=0.14) did not differ
      significantly in the first 15 days after transplantation. Long-term graft
      survival was similar in the two groups (88 vs 87%). INTERPRETATION: Desmopressin
      can be given to brain-dead donors to limit the harmful effects of diabetes
      insipidus without any substantial effects to graft function in recipients.

PMID- 9777835
TI  - In-vivo three-dimensional ultrasound reconstructions of embryos and early
      fetuses.
AB  - BACKGROUND: Three-dimensional (3D) imaging of the living human embryo has become
      possible in the monitoring of embryological development, as described by classic
      human embryology. We aimed to create 3D images of organs in embryos on early
      pregnancy. METHODS: We used a specially developed 7.5 MHz annular array 3D
      transvaginal probe to examine embryos. We included 34 women at 7-10 weeks'
      gestation. We measured the crown-rump length (CRL) of the embryos and fetuses and
      transferred the 3D ultrasound data to an external computer for further processing
      to calculate volume. FINDINGS: The CRLs ranged from 9.3 mm to 39.0 mm. The
      quality of the images of the embryos and fetuses made it possible to outline in
      detail the outer contours and the contours of the brain cavities, and the
      calculated volumes corresponded well to the descriptions from classic human
      embryology. INTERPRETATION: Our 3D imaging system allowed visualisation of
      structures of less than 10 mm. Therefore, development and abnormal development of
      fetuses can be monitored.

PMID- 9777836
TI  - Abnormal colonic fermentation in irritable bowel syndrome.
AB  - BACKGROUND: The cause of irritable bowel syndrome (IBS) is unknown. It may follow
      gastroenteritis and be associated with an abnormal gut flora and with food
      intolerance. Our study was designed to assess whether these factors were
      associated with colonic malfermentation. METHODS: We carried out a crossover
      controlled trial of a standard diet and an exclusion diet matched for
      macronutrients in six female IBS patients and six female controls. During the
      final 72 h on each diet, faecal excretion of fat, nitrogen, starch, and non
      starch polysaccharide NSP was measured, and total excretion of hydrogen and
      methane collected over 24 h in a purpose-built 1.4 m3 whole-body calorimeter.
      Breath hydrogen and methane excretion were then measured for 3 h after 20 g oral
      lactulose. FINDINGS: The maximum rate of gas excretion was significantly greater
      in patients than in controls (2.4 mL/min IQR 1.7-2.6 vs 0.6, 0.4-1.1). Although
      total gas production in patients was not greater than in controls (median 527
      mL/24 h IQR 387-660 vs 412, 234-507), hydrogen production was higher (332, 318
      478 vs 162, 126-217, p=0.009). In patients, the exclusion diet reduced symptoms
      and produced a fall in maximum gas excretion (0.5 mL/min IQR 0.3-0.7). After
      lactulose, breath hydrogen was greater on the standard than on the exclusion
      diet. INTERPRETATION: Colonic-gas production, particularly of hydrogen, is
      greater in patients with IBS than in controls, and both symptoms and gas
      production are reduced by an exclusion diet. This reduction may be associated
      with alterations in the activity of hydrogen-consuming bacteria. Fermentation may
      be an important factor in the pathogenesis of IBS.

PMID- 9777837
TI  - Never take things at face value.

PMID- 9777838
TI  - Effect of sleep deprivation on surgeons' dexterity on laparoscopy simulator.

PMID- 9777839
TI  - Functional anatomy of calorie fear in anorexia nervosa.

PMID- 9777840
TI  - Tissue transglutaminase and combined screening for coeliac disease and type 1
      diabetes-associated autoantibodies.

PMID- 9777841
TI  - Inducible nitric oxide synthase polymorphism and fatal cerebral malaria.

PMID- 9777842
TI  - Lack of T-cell proliferative response to HIV-1 antigens after 1 year of highly
      active antiretroviral treatment in early HIV-1 disease. Immunology Study Group of
      Spanish EARTH-1 Study.

PMID- 9777843
TI  - Treatment of retroperitoneal fibrosis by mycophenolate mofetil and
      corticosteroids.

PMID- 9777844
TI  - Detection of fetal RHD-specific sequences in maternal plasma.

PMID- 9777845
TI  - Diagnosis of spinal muscular atrophy from fetal normoblasts in maternal blood.

PMID- 9777846
TI  - Paramedic direct admission of heart-attack patients to a coronary-care unit.

PMID- 9777847
TI  - UN calls for positive approach to ageing.

PMID- 9777848
TI  - Consensus reached at new European breast-cancer meeting.

PMID- 9777849
TI  - Cartilage transplantation: an end to creaky knees?

PMID- 9777850
TI  - China's problems persist after the flood.

PMID- 9777851
TI  - India's welcome to foreign tobacco giants prompts criticism.

PMID- 9777852
TI  - Voluntary blood tests for Canadian doctors?

PMID- 9777853
TI  - Clinton administration plans to expand access to methadone.

PMID- 9777854
TI  - Escherichia coli O157:H7.
AB  - Escherichia coli O157 was first identified as a human pathogen in 1982. One of
      several Shiga toxin-producing serotypes known to cause human illness, the
      organism probably evolved through horizontal acquisition of genes for Shiga
      toxins and other virulence factors. E. coli O157 is found regularly in the faeces
      of healthy cattle, and is transmitted to humans through contaminated food, water,
      and direct contact with infected people or animals. Human infection is associated
      with a wide range of clinical illness, including asymptomatic shedding, non
      bloody diarrhoea, haemorrhagic colitis, haemolytic uraemic syndrome, and death.
      Since laboratory practices vary, physicians need to know whether laboratories in
      their area routinely test for E. coli O157 in stool specimens. Treatment with
      antimicrobial agents remains controversial: some studies suggest that treatment
      may precipitate haemolytic uraemic syndrome, and other studies suggest no effect
      or even a protective effect. Physicians can help to prevent E. coli O157
      infections by counselling patients about the hazards of consuming undercooked
      ground meat or unpasteurised milk products and juices, and about the importance
      of handwashing to prevent the spread of diarrhoeal illness, and by informing
      public-health authorities when they see unusual numbers of cases of bloody
      diarrhoea or haemolytic uraemic syndrome.

PMID- 9777855
TI  - Parity for mental illness, disparity for the mental patient.

PMID- 9777856
TI  - Time for reassessment of use of all medical information by UK insurers.

PMID- 9777857
TI  - Angels and spirits in the world of illness.

PMID- 9777858
TI  - High-dose chemotherapy and stem-cell support in breast cancer.

PMID- 9777859
TI  - Physiological or pathological chemokines.

PMID- 9777860
TI  - Physiological or pathological chemokines.

PMID- 9777861
TI  - Effect of early American results on patients in a tamoxifen prevention trial
      (IBIS). International Breast Cancer Intervention Study.

PMID- 9777862
TI  - Emergency contraception: WHO Task Force study.

PMID- 9777863
TI  - Emergency contraception: WHO Task Force study.

PMID- 9777864
TI  - Low carbohydrate intake and oral glucose-tolerance tests.

PMID- 9777865
TI  - Low carbohydrate intake and oral glucose-tolerance tests.

PMID- 9777866
TI  - Antiretroviral treatment.

PMID- 9777867
TI  - Bread fortification with folic acid, vitamin B12, and vitamin B6 in Hungary.

PMID- 9777868
TI  - British HIV Association guidelines.

PMID- 9777869
TI  - British HIV Association guidelines.

PMID- 9777870
TI  - Social context of meningococcal disease.

PMID- 9777871
TI  - Zidovudine and confusion in urinary metabolic screening.

PMID- 9777872
TI  - Osteoporosis, pregnancy, and lactation.

PMID- 9777873
TI  - Heart failure.

PMID- 9777874
TI  - Raised erythropoietin and thrombotic events.

PMID- 9777875
TI  - Assessing measles vaccination coverage by maternal recall in Guinea-Bissau.

PMID- 9777876
TI  - Freedom of information.

PMID- 9777877
TI  - Health care in Burma.

PMID- 9777878
TI  - The haunted forest: a ghost story.

PMID- 9777879
TI  - Magnesium in the management of asthma: critical review of acute and chronic
      treatments, and Deutsches Medizinisches Zentrum's (DMZ's) clinical experience at
      the Dead Sea.
AB  - The recognition of asthma as an inflammatory disease has led over the past 20
      years to a major shift in its pharmacotherapy. The previous emphasis on using
      relatively short-acting agents for relieving bronchospasms and for removing
      bronchial mucus has shifted toward long-term strategies with the use of inhaled
      corticosteroids, which successfully prevent and abolish airway inflammation.
      Because some of the biological, chemical, and immunological processes that
      characterize asthma also underly arthritis and other inflammatory diseases, and
      because many of these conditions have been successfully treated for the past 40
      years at the Dead Sea, we were not surprised to realize and record the
      significant improvement of asthmatic condition after a 4-week stay at the Dead
      Sea: lung function was improved, the number and severity of attacks was reduced,
      and the efficacy of beta2-agonist treatments was improved. After reviewing the
      acute and chronic treatments of asthma in the clinic (including emergency rooms)
      with magnesium compounds, and the use of such salts as supplementary agents in
      respiratory diseases, we suggest that the improvement in the asthmatic condition
      at the Dead Sea may be due to absorption of this element through the skin and via
      the lungs, and due to its involvement in anti-inflammatory and vasodilatatory
      processes.

PMID- 9777880
TI  - The validity and reliability of an asthma knowledge questionnaire used in the
      evaluation of a group asthma education self-management program for adults with
      asthma.
AB  - This paper reports aspects of the validity and reliability of an asthma general
      knowledge questionnaire for adults (AGKQA), developed as one of the outcome
      measures for a randomized controlled effectiveness trial of an asthma education
      program for adults with asthma. It also illustrates how study data can provide a
      valuable, generally neglected opportunity to assess the validity and reliability
      of a measure where resources are not available for the extensive investigation of
      these properties prior to administration of the measure in a study. The AGKQA was
      demonstrated to have good content and face validity. Construct validity assessed
      using the principal components method for factor analysis suggested the scale was
      unidimensional. Criterion-related validity, assessed using the contrasted groups
      method, demonstrated a significant difference (p < 0.0001) in total score and for
      68% of item responses for the adults with and without direct experience of
      asthma. The Kuder-Richardson 20 reliability coefficient for internal consistency
      calculated using responses at baseline, immediately, and 12 months post
      intervention were, respectively, 0.56, 0.80, and 0.75, indicating excellent
      reliability. The AGKQA is an acceptably valid and reliable measure for the
      assessment of program content mastery that it was designed to test.

PMID- 9777881
TI  - Young inner-city children visiting the emergency room (ER) for asthma: risk
      factors and chronic care behaviors.
AB  - Inner-city children visiting emergency rooms (ER) for asthma often rely on the ER
      as their primary source of care. To evaluate chronic asthma control, structured
      interviews were conducted with the adult accompanying a sample of 46 children, 2
      6 years old, presenting to an inner-city pediatric ER for asthma. Fifty-one
      percent had 10 or more prior ER visits and 46% had 2 or more previous
      hospitalizations. Seventy-two percent had functional severity scores in the
      moderate to severe range. Only 11% used daily inhaled anti-inflammatory
      medication. Not one patient had a written self-management plan. Most young
      children visiting an inner-city ER for asthma have poorly controlled and poorly
      managed chronic asthma.

PMID- 9777882
TI  - Development of an instrument to assess stress levels and quality of life in
      children with asthma.
AB  - The purpose of this study was to develop and evaluate a new instrument, About My
      Asthma (AMA), to assess stressors affecting quality of life in children with
      asthma. The AMA is a 55-item, 4-point Likert-type scale. Concurrent validity was
      established by comparing the AMA with the Pediatric Asthma Quality of Life
      Questionnaire (PAQLQ). Increased levels of stress measured by the AMA correlated
      with a decreased quality of life measured by the PAQLQ. We conclude that the AMA
      is a valid and reliable instrument to measure the quantity and type of stressors
      experienced by children who have asthma.

PMID- 9777883
TI  - Effects of beta2-agonists and budesonide on interleukin-1beta and leukotriene B4
      secretion: studies of human monocytes and alveolar macrophages.
AB  - The aims of the present study were to determine whether beta2-agonists (short-
      and long-acting) and a glucocorticoid (budesonide) influence the secretion of a
      pro-inflammatory cytokine (interleukin-1, [IL-1]) and a granulocyte attractant
      (leukotriene B4 [LTB4]) and to compare these effects on blood monocyte and
      alveolar macrophages. Alveolar macrophages (obtained by bronchoalveolar lavage)
      and blood monocytes from 26 healthy nonsmokers were stimulated with
      lipopolysaccharide or human serum opsonized zymosan. The influence of four beta2
      agonists (salbutamol, terbutaline, formoterol, and salmeterol) and a
      corticosteroid (budesonide) on the release of interleukin-1beta (IL-1beta) and
      LTB4 was studied in a dose-response manner (10(-8)-10(-5) mol/L for beta2
      agonists and 10(-10)-10(-6) mol/ L for budesonide). The stimulated IL-1beta
      secretion was significantly greater in blood monocytes than in alveolar
      macrophages (p < 0.05), but alveolar macrophages were much more capable of
      secreting LTB4 than were blood monocytes (p < 0.001). Budesonide significantly
      inhibited the release of IL-1beta from blood monocytes (p < 0.001), but no such
      effect was observed in alveolar macrophages. Budesonide did not influence the
      release of LTB4 in either cell type. The beta2-agonists neither influenced the
      LTB4 nor the IL-beta secretion in either cell type with the exception of
      formoterol, which stimulated IL-1beta secretion at the highest concentration (10(
      5) mol/L, p < 0.05). In conclusion, beta2-agonists exhibited only minor effects
      on IL-1beta secretion from blood monocytes and no effect on LTB4-secretion from
      either cell type, and budesonide effectively inhibited the IL-1beta release in
      blood monocytes, but not in alveolar macrophages. Thus, induced secretion of LTB4
      and IL-1beta , and the sensitivity to corticosteroids with regard to IL-1beta
      secretion, change during the transformation from blood monocytes to alveolar
      macrophages.

PMID- 9777884
TI  - Assessing metered-dose inhaler technique: comparison of observation vs. patient
      self-report.
AB  - The purpose of this study was to develop and determine the validity of a patient
      completed questionnaire that assesses metered-dose inhaler (MDI) technique. Self
      reported MDI technique was compared to observed technique. The questionnaire
      included nine steps for MDI use, with two to three response choices for each
      step. A total of 159 patients were studied. Direct observation revealed that
      greater than 82% of patients exhibited inadequate technique (more than two out of
      nine steps incorrect). The mean percentage agreement between the questionnaire
      and observation was 77.4%. Questionnaire results where in higher agreement with
      observation when patients performed correct MDI technique.

PMID- 9777885
TI  - The impact of asthma on health-related quality of life.
AB  - Although a substantial body of epidemiological and economic literature on asthma
      exists, relatively little is known about the impact of asthma on health-related
      quality of life (HRQL). The purpose of this review was to synthesize results from
      recent studies, profile the factors influencing HRQL in asthmatics, discuss the
      impact of treatment on HRQL outcomes, and offer recommendations for further
      research. The results of this review support the premise that asthma can
      adversely affect the physical, psychological, and social domains of HRQL.
      Published data suggest that females, those from lower socioeconomic groups, and
      ethnic minorities experience poorer quality of life as a result of their asthma
      symptoms. Results of published clinical trials indicate treatment regimens can
      have a significant impact on HRQL outcomes. Pharmacological interventions appear
      to effect change primarily in the physical domain and behavioral interventions
      lead to improvements in both physical and psychosocial domains. Future research
      should focus on precise a priori delineation of research hypotheses, including
      the selection of primary and secondary endpoints, the clarification and
      consistent application of criteria for defining asthma severity, thoughtful
      selection of HRQL instruments appropriate for the research hypotheses and target
      population, and careful delineation of clinically meaningful change scores of
      asthma-specific outcome measures.

PMID- 9777886
TI  - Molecular genetic features of myelodysplastic syndromes (MDS)
AB  - Recent developments in molecular genetics have provided insights on the molecular
      mechanisms that lead to myelodysplasias (MDS), secondary acute myelogenous
      leukemia (AML), therapy-induced AML, and elderly AML. These disorders are
      characterized by dysregulation of growth and differentiation of multilineage stem
      cells, a genetic profile characterized by unbalanced abnormalities that result in
      "unfavorable cytogenetics," and an increased frequency of intrinsic multidrug
      resistance. The unfavorable cytogenetics associated with this group of disorders
      include chromosome 5 and 7 monosomy, deletions of the long arm of chromosomes 5
      and 7, inversions of chromosome 3, translocations, deletions and trisomies
      involving several other chromosomes. Presumably, these unbalanced chromosomal
      aberrations result in hemizygosity and unmasking of oncogenes or inactivation of
      tumor suppressor genes. In addition, polymorphisms in genes encoding metabolic
      detoxification enzymes, defective DNA repair mechanisms, and intrinsic
      chromosomal instability have been implicated in the etiology of the
      myelodysplastic syndromes. It is evident that the cytogenetics associated with
      MDS are highly complex and heterogeneous. This review summarizes the most recent
      developments in the understanding of the molecular changes associated with the
      development of myelodysplasias and related leukemic disorders.

PMID- 9777887
TI  - Molecular genetics of human leukemia.
AB  - Human leukemias are clonal hemopathies generally characterized by acquired
      somatic mutations, including translocations, deletions, and insertions. Ten years
      ago, the first leukemia-related chromosomal translocation, the Philadelphia
      chromosome, was cloned and fully characterized at the molecular level. Since
      then, a plethora of chromosomal translocations and mutations has been associated
      with leukemogenesis. Analysis and comparison of this bewildering array of genetic
      changes have helped identify shared paradigms and themes in the mechanisms of
      transformation of hematopoietic cells. This information will guide the
      development of improved therapies that take into account the cytogenetic and
      molecular characteristics of human leukemias. This review summarizes the current
      knowledge of the nature of the genetic changes associated with leukemogenesis and
      discusses their consequences at the molecular and cellular levels.

PMID- 9777888
TI  - New agents for the treatment of acute myelogenous leukemia: focus on topotecan
      and retinoids.
AB  - Topotecan and retinoids are among the most promising agents being evaluated for
      the treatment of acute myelogenous leukemia (AML), refractory anemia with excess
      blasts (RAEB), and refractory anemia with excess blasts in transformation (RAEB
      t). Single-agent topotecan is similar to single-agent ara-C, but may be superior
      in patients with poor-prognosis chromosome abnormalities (ie, -5,-7). Topotecan
      plus ara-C is equivalent to topotecan alone in chronic myelomonocytic leukemia
      (CMML), but significantly more effective in RAEB and RAEB-t. Compared with single
      agent ara-C, the complete remission (CR) rate with topotecan plus ara-C is
      comparable, although it offers special advantages in patients with the -5,-7
      karyotype. In patients with poor-prognosis cytogenetics, the combination of
      cyclophosphamide, ara-C, and topotecan, plus all-trans retinoic acid (ATRA) and
      granulocyte colony-stimulating factor (G-CSF) appears favorable. In a recent
      study of triple-agent chemotherapy using fludarabine, ara-C, and idarubicin, with
      or without ATRA and G-CSF, median survival among poor-prognosis patients was 6-7
      months, but those who received ATRA did better than those who did not, primarily
      because it improved survival in those who did not achieve CR. G-CSF produced
      higher CR rates but had no effect on survival or disease-free survival.

PMID- 9777889
TI  - What is the best induction regimen for acute myelogenous leukemia?
AB  - The pursuit of the best induction regimen for acute myelogenous leukemia (AML)
      continues in an attempt to improve complete response rates and long-term disease
      free and overall survival. At this time, standard induction therapy generally
      consists of an anthracycline, most commonly daunorubicin given at a dose of 45-60
      mg/m2 intravenously for 3 days and cytarabine arabinoside (ara-C) given at a dose
      of 100-200 mg/m2 intravenously by continuous infusion for 7 days. This regimen is
      based on findings from classic studies conducted from the late 1960s through the
      1980s. Research on intensifying induction therapy has continued over the past
      decade. Potential strategies for intensifying induction therapy include (1)
      modulation of the anthracycline dose or agent; (2) modulation of ara-C; (3) the
      addition of other agents to standard induction therapy; (4) timed-sequential
      therapy; and (5) very early intensification therapy. Accurate interpretation of
      results from studies of intensifying induction therapy requires consideration of
      variables such as patient age, study inclusion criteria (eg, antecedent
      myelodysplasia), supportive care and, most importantly, patient selection.
      Furthermore, any benefit in long-term outcome during induction cannot be
      determined without regard to the choice of postremission therapy.

PMID- 9777890
TI  - Treatment of resistant disease.
AB  - Resistant AML encompasses two groups of patients: those with refractory leukemia
      and those whose leukemia has relapsed. Refractory leukemia is disease that does
      not respond to initial induction chemotherapy with cytarabine and an
      anthracycline. Patients with refractory leukemia are likely to have disease with
      adverse cytogenetics, a history of antecedent hematologic disturbance, adverse
      immunophenotypic features, and expression of multiple drug resistance. On the
      other hand, relapsed leukemia is leukemia that recurs following a CR. The
      duration of CR greatly affects the patient's prognosis and response to additional
      treatment. Patients with relapsed leukemia are heterogeneous with variable
      pretreatment characteristics.

PMID- 9777891
TI  - Allogeneic bone marrow transplantation for myelodysplastic syndrome: outcomes
      analysis according to IPSS score.
AB  - The objective of our analysis was to determine the post-transplantation outcomes
      for patients with myelodysplastic syndrome (MDS) according to their International
      Prognostic Scoring System (IPSS) risk categorization. Data for all MDS patients
      transplanted at our institution from 1981-1996 were reviewed. Multivariate
      analysis was used to determine factors predictive for non-relapse mortality,
      relapse, and disease-free survival. A total of 251 MDS patients (median age = 38
      years) were transplanted from 1981-1996. The overall disease-free survival rate
      was 40%, with an 18% relapse rate. Older age, increasing disease duration,
      mismatched donors, male gender, and therapy-related MDS were factors that
      significantly enhanced the likelihood of non-relapse mortality. Increasing
      disease duration, morphology, and cytogenetics were significant in predicting
      relapses. Increasing age, disease morphology, and cytogenetics were significant
      in determining disease-free survival. IPSS score was found to correlate
      significantly with relapse and disease-free survival. The 5-year disease-free
      survival was 60%, 36%, and 28% for low and intermediate-1 risk, intermediate-2
      risk, and high risk patients, respectively. We conclude that IPSS score may be
      used to predict relapse and disease-free survival in MDS patients undergoing
      allogeneic transplantation. Allogeneic transplantation may be recommended for
      patients with intermediate-1, intermediate-2, or high risk MDS.

PMID- 9777892
TI  - Umbilical cord transplantation.
AB  - The clinical efficacy of allogeneic bone marrow transplantation has been limited
      by difficulties in locating HLA-matched donors, and the occurrence of graft
      failure, severe graft-versus-host disease (GVHD), and opportunistic infections.
      Placental or umbilical cord blood may overcome some of these problems. Phase I-II
      trials of umbilical cord blood transplants (UCBT) show an overall engraftment
      rate of approximately 90%, with a median time to neutrophil recovery of 26 days.
      Nucleated cell, dose, and CFU-GM and CD34+ content were inversely correlated with
      the time to neutrophil recovery (P < .01 for each). The overall probability of
      grade II-IV GVHD was approximately 40%, despite high degrees of HLA disparity
      between donor and recipient. In analysis of data at two institutions, the only
      factors predictive of survival were age and cell dose within the context of HLA 0
      2 antigen disparities. There was no significant effect of HLA on the likelihood
      or speed of engraftment, the risk of grade II-IV acute GVHD, or survival. UCBT
      offers several potential advantages over bone marrow transplants for
      reconstitution of hematopoiesis, including the shorter interval to transplant,
      the absence of donor attrition, the absence of harvest complications, and the
      extremely low risk of cytomegalovirus transmission.

PMID- 9777893
TI  - Immunotherapy in acute myelogenous leukemia and myelodysplastic syndrome.
AB  - Disease recurrence following successful bone marrow transplantation remains a
      major impediment in the management of patients with acute myelogenous leukemia
      (AML) and myelodysplastic syndrome (MDS). A variety of monoclonal antibodies that
      deliver drugs or toxins to the site of activity, have been used in an attempt to
      augment marrow transplantation. Examples of three different monoclonal antibody
      techniques (naked antibody, drug antibody conjugations, and radiolabeled
      antibodies) are discussed. CD33 is an attractive antigen to use as a target for
      treating AML because it is present on most AML cells. Naked antibodies are
      limited in their ability to kill tumor cells, although studies to date suggest
      there may be a role in antileukemic therapy for unlabeled anti-CD33 humanized
      M195 antibody after the tumor burden has been reduced by chemotherapy.
      Calicheamicin, a novel and toxic drug moiety conjugated to anti-CD33 antibody, is
      currently under investigation in patients with refractory or relapsed AML.
      Results from a Phase I investigation were encouraging. Three different
      radiolabeled monoclonal antibodies have been evaluated in Phase I/II studies-
      131I-labeled anti-CD33 (p67) antibody, 213Bi-labeled humanized M195 antibody, and
      131I-anti-CD45 antibody. CD45 is a cell-surface antigen broadly expressed by all
      circulating leukocytes and lymphocytes. Initial studies demonstrated that
      substantially greater doses of radiation could be delivered to targeted organs
      compared with nontargeted organs using 131I-anti-CD45 antibody. This approach
      offers the potential for augmenting leukemia therapy without increased risk of
      toxicity.

PMID- 9777895
TI  - The role of apoptosis in the pathogenesis, prognosis, and therapy of hematologic
      malignancies.
AB  - Apoptosis or programmed cell death is a cellular process involved in the
      regulation of cell proliferation. Alterations in the expression of apoptosis
      related proteins are a common observation in hematologic malignancies. Moreover,
      increased expression levels of certain apoptosis-related proteins have been
      correlated with poorer clinical outcomes. Recent advances in the studies of the
      molecular events associated with the regulation of apoptosis have greatly
      improved our understanding of the etiology of human leukemias and
      myelodysplasias. Furthermore, these studies have helped identify proteins and
      cellular processes that are unique to leukemic cells and that could serve as
      therapeutic targets, diagnostic markers, and useful indicators of prognosis.
      Measurements of the levels of expression of apoptotic proteins could be used to
      help customize the therapeutic modalities that are most effective for each
      patient.

PMID- 9777894
TI  - Therapy of acute promyelocytic leukemia: all-trans retinoic acid and beyond.
AB  - Acute promyelocytic leukemia (APL) is the most potentially curable subtype of
      acute myeloid leukemia (AML). APL is highly sensitive to induction chemotherapy
      with anthracyclines. In addition, it now has been established that all-trans
      retinoic acid (ATRA), alone or in combination with chemotherapy for induction,
      improves the disease-free interval compared with chemotherapy alone. Large,
      prospective clinical studies have demonstrated complete remission rates ranging
      from 72% to 95% with ATRA therapy in patients with newly diagnosed APL. An
      important biological marker for monitoring residual disease is the promyelocytic
      retinoic acid receptor alpha (PML-RARalpha) fusion transcript. Its detection by
      the reverse transcription-polymerase chain reaction (RT-PCR) during remission
      appears to represent a strong predictor of clinical relapse. One limitation of
      ATRA therapy is the rapid development of retinoid resistance. Arsenic trioxide
      and alternative retinoids (9-cis retinoic acid and Am-80) currently are being
      investigated to determine whether they might have a role in circumventing
      retinoid resistance and further improving long-term outcome in patients with APL.

PMID- 9777896
TI  - The role of the MPL receptor in myeloproliferative disorders.
AB  - Thrombopoietin (TPO) is a primary regulator of megakaryopoiesis and
      thrombopoiesis, and has recently been identified as the ligand for the cytokine
      receptor MPL. Several lines of evidence suggest that dysregulation of MPL
      expression or TPO production are implicated in the pathogenesis of various
      myeloproliferative disorders. For example, mutations in the MPL gene can cause
      factor-independent growth and a transformed phenotype in vivo, and MPD may be
      associated with altered expression of the MPL receptor or TPO. Blast cells from
      patients with acute myelogenous leukemia (AML) often display MPL, and TPO induces
      some of these to proliferate. In sum, MPL may play a role as part of an autocrine
      pathway of MPD. While much remains to be clarified about the therapeutic use of
      TPO in AML, early results suggest it may be useful for platelet donation and/or
      priming to alleviate chemotherapy-induced thrombocytopenia in other malignant
      conditions.

PMID- 9777897
TI  - Platelet refractoriness and alloimmunization.
AB  - The two major methods of modifying donor blood products to prevent
      alloimmunization are leukocyte reduction or ultraviolet B (UVB) irradiation. Two
      studies have suggested that leukocyte reduction to levels <5 x 10(6) may be
      required to prevent alloantibody production. Three prospective, randomized
      transfusion trials demonstrated a statistically significant (P < 0.05) decrease
      in both platelet refractoriness and lymphocytotoxic antibody production in
      patients who received leukocyte-reduced blood components as compared to those who
      received standard unmodified blood products. The results of the Trial to Reduce
      Alloimmunization to Platelets (TRAP trial) further confirm the potential
      beneficial effects of leukocyte-reduced and UVB-irradiated blood products in
      preventing alloimmune platelet refractoriness. Five hundred thirty antibody
      negative patients undergoing induction chemotherapy for acute myeloid leukemia
      were randomly assigned to receive either unmodified platelet concentrates,
      filtered leukocyte-reduced platelet concentrates, UVB-irradiated platelet
      concentrates, or filtered leukocyte-reduced platelets obtained by apheresis.
      Patients who received modified platelet components had statistically
      significantly lower rates of both alloimmune platelet refractoriness and
      lymphocytotoxic antibodies than did patients who received unmodified platelet
      components. There were no differences in any study endpoints among patients who
      received any of the three modified platelet components. The investigators
      concluded that leukocyte-reduced and UVB-irradiated platelet components were
      equally effective in preventing alloimmune-mediated platelet refractoriness;
      platelets obtained by apheresis provided no additional benefit.

PMID- 9777898
TI  - Four decades of therapy for AML.
AB  - A review of the last four decades of leukemia research and treatment provides a
      view toward the next four decades. What is learned in leukemia research may apply
      to the treatment of other cancers. The biology of cancer, the importance of
      chromosomes, and the suppressor genes may hold the answers to future treatments.

PMID- 9777899
TI  - Preventing disability and managing chronic illness in frail older adults: a
      randomized trial of a community-based partnership with primary care.
AB  - BACKGROUND: Effective new strategies that complement primary care are needed to
      reduce disability risks and improve self-management of chronic illness in frail
      older people living in the community. OBJECTIVE: To evaluate the impact of a 1
      year, senior center-based chronic illness self-management and disability
      prevention program on health, functioning, and healthcare utilization in frail
      older adults. DESIGN: A randomized controlled trial. SETTING: A large senior
      center located in a northeast Seattle suburb. The trial was conducted in
      collaboration with primary care providers of two large managed care
      organizations. PARTICIPANTS: A total of 201 chronically ill older adults seniors
      aged 70 and older recruited through medical practices. INTERVENTION: A targeted,
      multi-component disability prevention and disease self-management program led by
      a geriatric nurse practitioner (GNP). MEASUREMENTS: Self-reported Physical
      function, physical performance tests, health care utilization, and health
      behaviors. RESULTS: Each of 101 intervention participants met with the GNP from 1
      to 8 times (median = 3) during the study year. The intervention group showed less
      decline in function, as measured by disability days and lower scores on the
      Health Assessment Questionnaire. Other measures of function, including the SF-36
      and a battery of physical performance tests, did not change with the
      intervention. The number of hospitalized participants increased by 69% among the
      controls and decreased by 38% in the intervention group (P = .083). The total
      number of inpatient hospital days during the study year was significantly less in
      the intervention group compared with controls (total days = 33 vs 116, P = .049).
      The intervention led to significantly higher levels of physical activity and
      senior center participation and significant reductions in the use of psychoactive
      medications. CONCLUSIONS: This project provides evidence that a community-based
      collaboration with primary care providers can improve function and reduce
      inpatient utilization in chronically ill older adults. Linking organized medical
      care with complementary community-based interventions may be a promising
      direction for research and practice.

PMID- 9777900
TI  - The effect of vitamin B12 deficiency on older veterans and its relationship to
      health.
AB  - OBJECTIVE: To examine the effect of vitamin B12 deficiency on older veterans and
      its relationship to general health and cognitive impairment. DESIGN: Cross
      sectional study. SETTING: Oklahoma City Veterans Affairs Medical Center.
      PARTICIPANTS: Data for this research were obtained from 303 ambulatory, older
      veterans who used the outpatient laboratories of the Oklahoma City Department of
      Veterans Affairs Medical Center. Subjects were included in the study if they were
      65 years of age and older and if they had no known diagnosis associated with B12
      deficiency. The sample in this study consisted of 301 men and 2 women aged 65 to
      89 years. MEASUREMENTS: This study used two separate measurements of vitamin B12
      deficiency: (1) a strict definition of B12 deficiency (serum B12 level <
      laboratory norm) and (2) a broader definition of B12 deficiency (serum B12 level
      < laboratory norm or laboratory norm < B12 < 300 pg/mL and methyl malonic acid
      (MMA) or homocysteine (HC) elevated by more than two standard deviations). The
      laboratory norm is 200 pg/mL. The dependent variables were measures of cognitive
      impairment and general health. Cognitive impairment was measured using the
      Folstein Mini-Mental State Examination (MMSE) and general health was measured
      using the RAND 36-Item Health Survey Version 1.0. The control variables for this
      study were the subjects' daily alcohol intake, daily intake of a vitamin/mineral
      supplement, annual income, and level of education. RESULTS/CONCLUSIONS: Nineteen
      subjects (6%) were vitamin B12-deficient as measured by the strict definition of
      B12 deficiency (serum B12 level < laboratory norm), and 49 subjects (16%) were
      vitamin B12-deficient as measured by the broader definition of B12 deficiency
      (serum B12 level < laboratory norm or laboratory norm < B12 < 300 pg/mL and MMA
      or HC elevated by more than two standard deviations). Vitamin B12 level decreases
      as age increases. Of the nine general health outcomes measured by using the RAND
      36-Item Health Survey, only bodily pain is associated with vitamin B12
      deficiency, and only then when B12 deficiency is measured as serum B12 level <
      laboratory norm, the strict definition of B12 deficiency. Vitamin B12-deficient
      subjects experience more bodily pain than those with normal vitamin B12 levels.
      There is a significant difference between B12-deficient subjects and B12 normal
      subjects on cognitive impairment, with B12 normal subjects indicating less
      cognitive impairment, only when B12 deficiency is measured as B12 level <
      laboratory norm, the strict definition of B12 deficiency. The broader measurement
      of vitamin B12 deficiency (i.e., serum B12 level < laboratory norm or laboratory
      norm < B12 < 300 pg/mL and MMA or HC elevated by more than two standard
      deviations) is not a significant correlate of cognitive impairment and general
      health.

PMID- 9777901
TI  - Exercise to improve spinal flexibility and function for people with Parkinson's
      disease: a randomized, controlled trial.
AB  - OBJECTIVES: The effectiveness of an exercise intervention for people in early and
      midstage Parkinson's disease (stages 2 and 3 of Hoehn and Yahr) in improving
      spinal flexibility and physical performance in a sample of community-dwelling
      older people is described. DESIGN AND SETTING: Fifty-one men and women, aged 55
      84 years, identified through advertisement, local support groups, and local
      neurologists were enrolled into a randomized, controlled trial. Subjects were
      assigned randomly to an intervention or a usual care arm (i.e., no specific
      exercise). Of the original 51 participants, 46 completed the randomized,
      controlled trial. Participants in the exercise arm (n = 23) received individual
      instruction three times per week for 10 weeks. Participants in the usual care arm
      (n = 23) were "wait listed" for intervention. MEASUREMENTS: Changes over 10 weeks
      in spinal flexibility (i.e., functional axial rotation) and physical performance
      (i.e., functional reach, timed supine to stand) were the primary outcome
      measures. RESULTS: MANOVA conducted for the three primary outcome variables
      demonstrated significant differences (P < or = .05) between the two groups.
      Further analysis using ANOVA demonstrated significant differences between groups
      in functional axial rotation and functional reach for the intervention compared
      with the control group. There was no significant difference in supine to sit
      time. CONCLUSION: Study results demonstrate that improvements in axial mobility
      and physical performance can be achieved with a 10-week exercise program for
      people in the early and midstages of PD.

PMID- 9777902
TI  - The association of non-insulin-dependent diabetes mellitus and cognitive function
      in an older cohort.
AB  - OBJECTIVE: In this study, we examined the association of non-insulin-dependent
      diabetes mellitus (NIDDM) and impaired glucose tolerance (IGT) with cognitive
      function in a population-based sample of older individuals. RESEARCH DESIGN AND
      METHODS: Subjects were 1509 healthy, community-dwelling men and women aged 55
      years and older who were participants in the Rancho Bernardo Study and attended
      clinic visits in 1984-87 and in 1988-91. An oral glucose tolerance test was
      administered during the 1984-87 visits. Based on World Health Organization
      criteria, participants were classified into those with NIDDM, IGT, or normal
      glucose tolerance. During the 1988-91 clinic visits, 12 tests of cognitive
      function were administered. RESULTS: Of the participants, 14.3% of the men and
      9.9% of the women had NIDDM, and 21.0% of the men and 28.0% of the women had IGT.
      Multiple regression analysis was used to compare the cognitive function of
      individuals with NIDDM and IGT with individuals with normal glucose tolerance
      after adjustment for age, education, obesity, depression, blood pressure, and
      current estrogen use. In men, there were no statistically significant differences
      in any of the 12 cognitive function tests by glucose tolerance category. Compared
      with those with normal glucose tolerance, women with IGT had lower scores on
      almost every cognitive function test, whereas women with NIDDM had higher scores,
      but none of these differences were statistically significant after adjustment for
      multiple comparisons. Furthermore, observed differences by NIDDM or IGT status
      were small and accounted for < or = 0.6% of the explained variance in cognitive
      function. CONCLUSIONS: This study shows no strong or consistent association
      between IGT or mild diabetes with cognitive function in community-dwelling older
      adults.

PMID- 9777903
TI  - The association of weight change in Alzheimer's disease with severity of disease
      and mortality: a longitudinal analysis.
AB  - OBJECTIVE: To describe weight loss in relation to the severity of Alzheimer's
      disease (AD), to identify confounders that might account for weight loss, and to
      investigate the association of weight change with mortality. METHODS: This study
      included 666 subjects with AD from the Consortium to Establish a Registry for
      Alzheimer's Disease, a longitudinal study of subjects with AD studied for < or =
      6 years. Body weight was measured on entry and at annual follow-up examinations
      as part of standardized clinical assessments. Hierarchical linear models were
      used to estimate weight change per change in stage of AD, as measured by the
      Clinical Dementia Rating scale, and to assess the impact of possible confounders
      on the tendency for weight loss. Linear correlation of the trajectories of weight
      and CDR over time were used to determine the association between weight change
      and stage change. The association between weight change and mortality was modeled
      using the Cox proportional hazards model. RESULTS: Each change in stage of AD was
      associated with an estimated average weight loss of nearly 2 lb (P = .0001). The
      correlation between change in stage of AD and weight change was statistically
      significant (r = -0.09, P = .005), which indicates a greater tendency toward
      weight loss with progression of AD. Weight loss of > or = 5% in any year before
      death was a significant predictor of mortality. When weight loss in the year
      before death or censoring was analyzed as a continuous variable, it was a
      significant predictor of mortality. Additionally, the relative risk of death
      increased as weight loss increased. In contrast, weight gain decreased the risk
      of mortality. CONCLUSION: The risk of weight loss tends to increase with severity
      and progression of AD. Weight loss is a predictor of mortality among subjects
      with AD, whereas weight gain appears to have a protective effect.

PMID- 9777904
TI  - Correlates of prescription and over-the-counter medication usage among older
      Mexican Americans: the Hispanic EPESE study. Established Population for the
      Epidemiologic Study of the Elderly.
AB  - OBJECTIVES: To determine the prevalence rates of prescription and over-the
      counter (OTC) medication usage among community-dwelling older Mexican Americans.
      DESIGN: Cross-sectional survey of a regional probability sample of older Mexican
      Americans. SETTING: The 1992-1997 Hispanic Established Population for the
      Epidemiologic Study of the Elderly (H-EPESE), a probability sample of
      noninstitutionalized Mexican Americans, age 65 and over, living in the five
      Southwestern states of Texas, New Mexico, Colorado, Arizona, and California.
      PARTICIPANTS: 2899 persons, age 65 and over, considered Mexican American, using
      appropriate weighting procedures to produce regional estimates. OUTCOME MEASURES:
      Use of prescription and OTC medication within the last 2 weeks before the survey
      confirmed by in-home review of medication containers. RESULTS: Medication users
      consumed a mean of 2.9 prescription and 1.3 OTC medications. Over half (58.9%, n
      = 1,798) of the participants used at least one prescribed medication, and 31.3%
      (n = 847) used at least one OTC medication within the 2 weeks before their
      participation in the study. Factors associated with both prescription and OTC
      medication usage were self-perceived health and number of co-morbid conditions.
      Factors associated only with prescription medication usage included female
      gender, alcohol usage, ADL dependency, and presence of additional insurance.
      Structural assimilation was associated only with OTC medication usage.
      CONCLUSIONS: These data show lower prevalence rates of prescription medication
      usage among Mexican American older men and lower rates of OTC medication usage in
      older Mexican Americans of both genders than previously reported in other ethnic
      groups. This may reflect differences in time and geographic location of the
      Hispanic EPESE relative to other EPESE studies, ethnic differences in access to
      care as reflected by insurance in addition to Medicare, ethnic differences in
      survival, especially among males, or ethnic differences in medication
      preferences.

PMID- 9777905
TI  - Discussions about end-of-life care in nursing homes.
AB  - OBJECTIVE: To measure the frequency with which nursing home residents and their
      surrogates discuss with clinicians the resident's wishes concerning future
      treatment and to assess the influence of the Patient Self Determination Act
      (PSDA) on the frequency and nature of such discussions. DESIGN: Retrospective
      cohort study of residents admitted to nursing homes before and after the PSDA.
      SETTING: Six large (at least 120 licensed chronic care beds), randomly selected
      nursing homes in Connecticut. PARTICIPANTS: Six hundred randomly selected nursing
      home residents admitted during 1990 and 1994 to one of the six study nursing
      homes. MEASUREMENTS: Documented discussions concerning future treatment wishes
      were abstracted from residents' nursing home medical records. Participants in the
      discussion, as well as the timing (i.e., date) and content of the documented
      discussions were recorded. Sociodemographic and health status factors were also
      obtained from the medical record. RESULTS: A large majority of residents (71.5%)
      had no discussion of future treatment wishes documented in their medical record.
      However, the percentage of residents with documented discussions had increased
      since the implementation of the PSDA (36.7% post-PSDA vs 20.3% pre-PSDA). Of
      those in the post-PSDA cohort who had had discussions, 90% had only one
      discussion within the first year of admission, and more than half (58.1%) of
      those who had discussions discussed only life-support systems (cardiopulmonary
      resuscitation, artificial nutrition and hydration, and ventilation) rather than
      broader preferences for future treatment, including proxy decision-making.
      CONCLUSIONS: Despite the increased prevalence of discussions about future
      treatment wishes since the enactment of the PSDA, no discussions were documented
      for most residents. For those with documented discussions, such conversations
      occurred rarely and were narrow in scope, suggesting that residents' and
      families' roles in medical decision-making in nursing homes may be limited.

PMID- 9777907
TI  - Beliefs concerning death, dying, and hastening death among older, functionally
      impaired Dutch adults: a one-year longitudinal study.
AB  - OBJECTIVES: Population surveys have documented increasing public support for
      euthanasia and assisted suicide but have not focused on the population of
      chronically ill older persons, obtained detailed sociocultural or health status
      information, or performed repeat assessments. This study seeks to describe the
      views of functionally-impaired Dutch elders on death, dying, and hastened death
      and to relate these to sociocultural and health status. DESIGN: One-year
      prospective epidemiologic survey. SETTING AND PARTICIPANTS: Community-dwelling
      participants in the longitudinal component of the Groningen Longitudinal Aging
      Study were assessed at home by interview and questionnaire in 1994 (n = 632) and
      again in 1995 (n = 575). MEASUREMENTS: Independent variables were sociocultural
      characteristics (eg, age, sex, income, education, religious affiliation, strength
      of religious belief), physical health status (number of chronic medical
      conditions, functional impairments), and mental health status (life satisfaction,
      self-efficacy, anxiety, depression, and neuroticism). Dependent variables were
      preoccupation with and fear of death, fears of the dying process, and attitudes
      toward hastened death. RESULTS: Low and stable rates of preoccupation with death
      and fear of death were found. Occasional but not persistent fears about the dying
      process were common. Fears of death and dying were most closely related to health
      status, especially mental health status. Views concerning hastening death were
      most strongly related to sociocultural variables, especially religious belief and
      affiliation. There was little change over the 1-year follow-up, with a trend
      toward less fears of death and dying and less support for hastened death.
      Significant changes in fears of death and dying and attitudes toward hastened
      death were not seen even in the 25% of subjects with the greatest deterioration
      in activities of daily living or greatest increase in anxiety and depression
      during the 1-year follow-up. CONCLUSION: Beliefs about death, dying, and hastened
      death are stable over 1-year follow-up. Fears of death and dying are most
      strongly related to mental health in this community sample. Attitudes about
      hastening death are primarily related to religious belief and secondarily to
      mental health. Mental health factors may determine the distress associated with
      the prospect of death and dying, whereas religion may dictate the actions
      considered proper when dying.

PMID- 9777906
TI  - Influence of patient preferences and local health system characteristics on the
      place of death. SUPPORT Investigators. Study to Understand Prognoses and
      Preferences for Risks and Outcomes of Treatment.
AB  - OBJECTIVE: To examine the degree to which variation in place of death is
      explained by differences in the characteristics of patients, including
      preferences for dying at home, and by differences in the characteristics of local
      health systems. DESIGN: We drew on a clinically rich database to carry out a
      prospective study using data from the observational phase of the Study to
      Understand Prognoses and Preferences for Outcomes and Risks of Treatments
      (SUPPORT component). We used administrative databases for the Medicare program to
      carry out a national cross-sectional analysis of Medicare enrollees place of
      death (Medicare component). SETTING: Five teaching hospitals (SUPPORT); All U.S.
      Hospital Referral Regions (Medicare). STUDY POPULATIONS: Patients dying after the
      enrollment hospitalization in the observational phase of SUPPORT for whom place
      of death and preferences were known. Medicare beneficiaries who died in 1992 or
      1993. MAIN OUTCOME MEASURES: Place of death (hospital vs non-hospital). RESULTS:
      In SUPPORT, most patients expressed a preference for dying at home, yet most died
      in the hospital. The percent of SUPPORT patients dying in-hospital varied by
      greater than 2-fold across the five SUPPORT sites (29 to 66%). For Medicare
      beneficiaries, the percent dying in-hospital varied from 23 to 54% across U.S.
      Hospital Referral Regions (HRRs). In SUPPORT, variations in place of death across
      site were not explained by sociodemographic or clinical characteristics or
      patient preferences. Patient level (SUPPORT) and national cross-sectional
      (Medicare) multivariate models gave consistent results. The risk of in-hospital
      death was increased for residents of regions with greater hospital bed
      availability and use; the risk of in-hospital death was decreased in regions with
      greater nursing home and hospice availability and use. Measures of hospital bed
      availability and use were the most powerful predictors of place of death across
      HRRs. CONCLUSIONS: Whether people die in the hospital or not is powerfully
      influenced by characteristics of the local health system but not by patient
      preferences or other patient characteristics. These findings may explain the
      failure of the SUPPORT intervention to alter care patterns for seriously ill and
      dying patients. Reforming the care of dying patients may require modification of
      local resource availability and provider routines.

PMID- 9777908
TI  - An operation under general anesthesia as a risk factor for age-related cognitive
      decline: results from a large cross-sectional population study.
AB  - OBJECTIVE: To evaluate the factor 'operation under general anesthesia' as a
      possible risk factor for age-related cognitive decline. DESIGN: A retrospective,
      population-based, cross-sectional study. SETTING: Maastricht Aging Study (MAAS),
      Maastricht, The Netherlands. PARTICIPANTS: 1257 normal healthy subjects aged 24
      to 86 years. Of the 1257 healthy subjects, 946 subjects appeared to have
      undergone at least one operation under general anesthesia. MEASUREMENTS: The
      history of an operation under general anesthesia, number of operations, duration
      of anesthesia, cognitive performance, subjective health, and subjective memory
      were measured. RESULTS: A history of an operation under general anesthesia, the
      number of operations, and the total duration of anesthesia significantly
      contributed to the number of subjective health-related complaints but did not
      predict cognitive performance or memory complaints. Subjects with a history of an
      operation under general anesthesia felt less healthy than subjects who had never
      undergone an operation under general anesthesia. No interactions with age were
      found. CONCLUSION: The present study found no support for the notion that a
      history of an operation under general anesthesia is a determinant or risk factor
      for accelerated age-related cognitive decline.

PMID- 9777909
TI  - Clock drawing test in very mild Alzheimer's disease.
AB  - OBJECTIVES: The primary objective of this study was to determine the efficacy of
      the clock drawing test to predict the presence of very mild Alzheimer's disease
      (AD). A secondary objective was to identify elements of clock drawing that were
      most useful in differentiating cognitively intact older adults from those with
      mild Alzheimer's disease. DESIGN: Cohort based comparison of retrospective data.
      SETTING: Academic research center. PARTICIPANTS: Clock drawings from 41
      outpatient cases of mild AD with Mini-Mental State Exam scores of 24 or higher
      and 39 age- and education-matched older adults were scored. MEASUREMENTS: Clock
      drawings were blindly and independently scored by two raters using the Clock
      Drawing Interpretation Scale and the scoring system reported by Rouleau et al.
      Predictive values for positive and negative tests were calculated using cut-off
      scores for total score and component subscores from each of these two systems.
      RESULTS: Two or more errors in the depiction of the clock hands on the Clock
      Drawing Interpretation Scale had a positive predictive value for AD of 100% and a
      negative predictive value of 51%. A score of 2 or less on the 4-point hand
      placement component of the Rouleau et al. scoring system provided a positive
      predictive value for AD of 94% and was associated with a negative predictive
      value of 62%. CONCLUSION: An individual who commits two errors or more in drawing
      the clock hands deserves further investigation for a possible dementia. Normal
      hand placement on the clock drawing test does not exclude AD. However, when
      prevalence rates of dementia in community-dwelling older adults are considered,
      these results argue that normal clock hand placement indicates that dementia is
      unlikely.

PMID- 9777910
TI  - The relationship between insomnia and mortality among community-dwelling older
      women.
AB  - OBJECTIVES: To investigate the relationship between insomnia and 6-year survival
      among older, community-dwelling, white women. DESIGN: Longitudinal study.
      SETTING: The sample was selected randomly from a 20-census tract area of
      Baltimore, Maryland. PARTICIPANTS: In 1984, 778 women aged 65 years and older
      participated in the baseline survey; 613 were re-interviewed in 1985; 596 were
      reinterviewed in 1986. MEASUREMENTS: Insomnia was measured as self-report of at
      least one of three sleep complaints: trouble initiating sleep, waking at night
      and trouble falling back to sleep, and waking too early. Cox proportional hazards
      models were used to assess the relationship between insomnia, as reported at the
      most recent of three interviews, and mortality. RESULTS: Twenty-nine percent of
      the sample reported trouble initiating sleep, 22.4% reported waking at night and
      having trouble falling back to sleep, and 26.6% reported waking too early. Of the
      sample, 43.2% had insomnia at the baseline interview; 23.2% percent of
      respondents with insomnia at baseline died during the follow-up period compared
      with 22.0% of those without insomnia at baseline. Recent insomnia was not
      associated significantly with mortality in either crude analyses (Hazards Ratio
      (HR) = 1.11, 95% CI, 0.78-1.60) or analyses adjusted for age, prescription
      medication use, functional limitations, self-rated health, and number of chronic
      conditions (HR = 0.74, 95% CI, 0.50-1.09). CONCLUSION: Our results, combined with
      the results from previous studies, suggest strongly that insomnia is not an
      indicator of approaching mortality in older community-dwelling populations.

PMID- 9777912
TI  - Association of electrocardiographic left ventricular hypertrophy with the
      incidence of new congestive heart failure.
AB  - OBJECTIVE: To investigate the association of electrocardiographic (ECG) left
      ventricular hypertrophy (LVH) with the incidence of new congestive heart failure
      (CHF) in older people. DESIGN: In a prospective study of 2638 older people, ECGs
      were obtained at study entry, at 1 month after study entry, when clinically
      indicated, and at least yearly after study entry. ECG LVH was diagnosed if the
      point score of Romhilt and Estes was > or = 5. Persistent LVH was diagnosed if
      all of the ECGs showed LVH. New LVH was diagnosed if the baseline ECG showed no
      LVH but LVH was present on the last ECG. Regression of LVH was diagnosed if the
      baseline ECG showed LVH but no LVH was present on the last ECG. No LVH was
      diagnosed if all of the ECGs showed no LVH. Persistent LVH, new LVH, regression
      of LVH, and no LVH were correlated with the incidence of new CHF at follow-up.
      SETTING: A large long-term health care facility. PATIENTS: The patients included
      1805 women and 833 men, mean age 81 +/- 9 years (range 60 to 103). MEASUREMENTS
      AND MAIN RESULTS: Of the 2,638 older persons studied, 281 (11%) had persistent
      ECG LVH, 31 (1%) had new ECG LVH, 12 (0.5%) had regression of ECG LVH, and 2314
      (88%) had no ECG LVH. At 42 +/- 24 months (range 1 to 154 months) follow-up, new
      CHF developed in 168 of 281 persons (60%) with persistent LVH, in 16 of 31
      persons (52%) with new LVH, in 4 of 12 persons (33%) with regression of LVH, and
      in 507 of 2314 persons (22%) with no LVH. Kaplan-Meier survival curves showed
      that the development of new CHF was higher in persons with persistent LVH versus
      regression of LVH (P = .013), in persons with persistent LVH versus no LVH (P =
      .001), in persons with new LVH versus regression of LVH (P = .039), and in
      persons with new LVH versus no LVH (P = .001). CONCLUSION: Older persons with
      persistent or new ECG LVH have a higher incidence of new CHF and an earlier time
      to the development of new CHF than older persons without ECG LVH.

PMID- 9777913
TI  - Contribution of individual items to the performance of the Norton pressure ulcer
      prediction scale.
AB  - OBJECTIVES: To assess the specific contribution to overall scale performance of
      each of the five items that constitute the Norton pressure ulcer prediction
      scale. DESIGN: A comparison of statistical models based on cross-sectional
      surveys of hospitalized patients. SETTING: An urban teaching hospital in Geneva,
      Switzerland. PARTICIPANTS: 2373 hospitalized patients who were free of pressure
      ulcers on admission. MEASUREMENTS: Norton scale items measuring activity,
      mobility, physical condition, mental condition, and incontinence on a 4-point
      scale were examined as predictors of stage 1 or greater pressure ulcers. RESULTS:
      A total of 245 new pressure ulcers occurred between admission and patient
      observation. After adjustment for other independent predictors in proportional
      hazards models, only the activity and mobility items remained associated
      significantly with the risk of pressure ulcer. A simplified 2-item scale was more
      strongly associated with pressure ulcer risk than was the classic 5-item Norton
      scale. CONCLUSIONS: Our study suggests that the activity and mobility items of
      the Norton scale are sufficient to express the risk of pressure ulcers in
      hospitalized patients. Confirmation of this finding in prospective studies is
      warranted.

PMID- 9777911
TI  - Arginine vasopressin levels in nursing home residents with nighttime urinary
      incontinence.
AB  - OBJECTIVES: To examine the relationship between diurnal urine volume and plasma
      arginine vasopressin levels (AVP) in nursing home residents with nighttime
      urinary incontinence and a comparison group of frail but nondemented, continent
      geriatric board and care residents. DESIGN: Case series. SETTING: Four nursing
      homes and two board and care facilities. PARTICIPANTS: Sixty-two nursing home
      residents and 27 board and care residents. MEASUREMENTS: Daytime (7:00 a.m. to
      7:00 p.m.) and nighttime (7:00 p.m. to 7:00 a.m.) urine volumes of incontinent
      nursing home residents were measured over 3 days and 3 nights by reweighing
      preweighed adults diapers and toileting inserts emptied by research staff for the
      comparison group. AVP levels were drawn in the early morning (5:00 a.m. to 7:00
      a.m.) before subjects arose and in the evening after an hour of lying in bed
      (8:00 p.m. to 11:00 p.m.), and plasma levels were determined by radioimmunoassay.
      RESULTS: Half of the nursing home residents and 82% of the comparison group had
      night/total urine volume ratios > or = 50%. Forty-nine percent of the total of 89
      subjects had undetectable morning AVP levels, 61% had undetectable evening AVP
      levels, and 42% had undetectable AVP levels in both morning and evening. There
      were no significant differences in AVP levels between those with night/total
      urine volume ratios > or = 50% and < 50% in either the nursing home or comparison
      groups though the small number of comparison group subjects with ratios < 50% may
      have limited our statistical power to detect differences. CONCLUSION: Our data
      suggest that a substantial proportion of both nursing home residents with
      nighttime incontinence and frail geriatric patients with a reversal of the normal
      diurnal pattern of urine excretion have an accompanying deficiency in AVP
      production and/or secretion. More detailed physiologic studies are needed to
      understand better the pathophysiology of geriatric nocturia and nighttime
      incontinence and the role that AVP deficiency may play in these conditions. Until
      such studies are carried out, we do not recommend the routine use of exogenous
      AVP for geriatric patients with unexplained nocturnal polyuria.

PMID- 9777914
TI  - On the number of automated timed manual performance trials to administer.
AB  - OBJECTIVE: To determine the number of trials needed to obtain satisfactory
      results when evaluating function in older subjects using the automated version of
      the Williams short (three-door) Timed Manual Performance (TMP) test. DESIGN:
      Administration of from one to five trials in succession on a given test date.
      SETTING: A Continuing Care Retirement Community (CCRC), assisted living centers,
      nursing homes, and a community residence, all located in central North Carolina.
      PARTICIPANTS: The subject population consisted of 182 older volunteers, aged 63
      to 100 years. One hundred nineteen lived independently in a CCRC, 33 were
      assisted-living residents, 29 lived in nursing homes, and one lived independently
      in the community. Each subject was administered at least three trials in
      succession on his or her first test date; 23 of the independently living CCRC
      residents were given three trials on a second test date. The community-dwelling
      volunteer was administered from one to five trials on each of 26 test dates over
      an approximately 16-month period. MEASUREMENTS: The time it takes to perform five
      door opening and closing operations as measured by the three-door Cognatemp
      Automated Timed Manual Performance (ATMP) system. MAIN RESULTS: Average ATMP time
      for the subjects living independently decreased approximately 10% between the
      first two trials but negligibly between trials two and three. The more dependent
      groups continued to improve between trials two and three. The community-dwelling
      subject tended to improve in the first three or four trials and to decline by the
      fifth trial. CONCLUSIONS: It is recommended that two trials be administered and
      the best time used; if neither trial results in a time less than 10 seconds, one
      or two more trials should be administered. It is generally not necessary nor
      advantageous to administer more than four trials.

PMID- 9777915
TI  - Epilepsy in older adults: causes, consequences and treatment.
AB  - OBJECTIVES: Seizures and epilepsy are common problems in older adults. Although,
      the highest incidence of seizures and epilepsy occurs in individuals more than 65
      years of age, the magnitude of this public health problem, and its consequences
      on the quality of life of older adults, are not appreciated. Moreover, there is
      no consensus on the most appropriate way to diagnose or manage epilepsy in this
      population. This report reviews the current literature on all aspects of epilepsy
      in older people. DESIGN/METHODS: The medical literature was reviewed for all
      articles pertaining to pathophysiology, diagnosis, and treatment of epilepsy in
      older people. RESULTS: Epidemiology, etiology, diagnosis, use of diagnostic tests
      including EEG and imaging, new medical and surgical treatments, and psychosocial
      issues as they relate to older epilepsy patient are discussed. Several questions
      that merit future systematic investigation are presented. CONCLUSION: Seizures
      and epilepsy in older people are much more common than is generally known. There
      are unique issues related to this population with regard to diagnosis and
      treatment. Several new medical and surgical therapies are now available for all
      epilepsy patients, some of which may be helpful for the older epilepsy patient.

PMID- 9777916
TI  - Therapy for acute myocardial infarction in older persons.
AB  - OBJECTIVE: To review the early management of acute myocardial infarction (AMI) in
      older adults. METHODS: Recently published studies relevant to the early
      management of AMI were systematically reviewed. When possible, the impact of
      older age on complication rates and clinical outcomes was evaluated. RESULTS: In
      general, AMI therapies that are effective in younger patients are also effective
      in older patients. Conversely, older age is associated with an increased risk of
      complications from therapy, implying that careful patient selection is required
      to optimize outcomes while minimizing risks. The principal limitation of
      currently available data is that relatively few patients older than the age of 80
      have been enrolled in prospective randomized clinical trials. CONCLUSIONS:
      Thrombolysis and primary angioplasty are effective in establishing reperfusion
      and improving clinical outcomes in older patients with AMI. In the absence of
      contraindications, aspirin and beta blockers should be considered standard
      therapy in AMI patients of all ages, whereas heparin, nitrates, and angiotensin
      converting enzyme inhibitors are indicated in selected subgroups. At the present
      time, calcium channel blockers, magnesium, and antiarrhythmic agents are not
      recommended for routine use in the AMI setting, and the role of glycoprotein
      IIb/IIIa inhibitors, low molecular weight heparin, and other newer agents await
      the results of ongoing clinical trials.

PMID- 9777917
TI  - Informed consent for research on human subjects with dementia. AGS Ethics
      Committee. American Geriatrics Society.

PMID- 9777918
TI  - The war on health care fraud and abuse: peril for providers.

PMID- 9777919
TI  - Preventing disability in older people with chronic disease: what is a doctor to
      do?

PMID- 9777920
TI  - Vitamin B12 deficiency in older people: improving diagnosis and preventing
      disability.

PMID- 9777921
TI  - Health care system structure and function--and outcomes.

PMID- 9777922
TI  - Combination therapy for early Alzheimer's disease: what are we waiting for?
AB  - The practical pharmacological approaches currently available to palliate the
      cognitive and functional losses in early Alzheimer's disease (AD) include
      cholinesterase inhibitors (ChEI), antioxidants (e.g., vitamin E), anti
      inflammatory agents, estrogen, seligiline, vasoactive agents, and ginkgo biloba.
      Reviewing available data on these therapies and using models from medical
      illnesses such as cancer and hypertension, we highlight the urgent need for
      evaluating combination therapies in early AD.

PMID- 9777923
TI  - Compensatory driving strategy of older people may increase driving risk.

PMID- 9777924
TI  - Concordance for psychotropic drug use in older married couples.

PMID- 9777925
TI  - Increasing the quality of medical care in the nursing home setting.

PMID- 9777926
TI  - Predicting mortality in patients with bacteremia.

PMID- 9777927
TI  - Depression and wealth in older people: when money makes the difference.

PMID- 9777928
TI  - Exposure to domestic cats or dogs: risk factor for Pasteurella multocida
      pneumonia in older people?

PMID- 9777929
TI  - Speech disturbance and marked decrease in function seen in several older patients
      on olanzapine.

PMID- 9777930
TI  - Effect of DNA repair inhibitors on the in vitro test for Alzheimer's disease.

PMID- 9777931
TI  - Forty years of the Warner-Lambert/Parke-Davis Award: a remarkable record.

PMID- 9777932
TI  - Warner-Lambert/Parke-Davis Award lecture. Many tumors and many genes: genetics of
      uterine leiomyomata.

PMID- 9777933
TI  - Atherosclerosis in young people: the value of the autopsy for studies of the
      epidemiology and pathobiology of disease.

PMID- 9777934
TI  - Risk factors and progression of atherosclerosis in youth. PDAY Research Group.
      Pathological Determinants of Atherosclerosis in Youth.

PMID- 9777935
TI  - Chronic inflammation: links with angiogenesis and wound healing.

PMID- 9777937
TI  - Homogeneous multiplex genotyping of hemochromatosis mutations with fluorescent
      hybridization probes.
AB  - Multiplex polymerase chain reaction amplification and genotyping by fluorescent
      probe melting temperature (Tm) was used to simultaneously detect multiple
      variants in the hereditary hemochromatosis gene. Homogenous real-time analysis by
      fluorescent melting curves has previously been used to genotype single base
      mismatches; however, the current method introduces a new probe design for
      fluorescence resonance energy transfer and demonstrates allele multiplexing by Tm
      for the first time. The new probe design uses a 3'-fluorescein-labeled probe and
      a 5'-Cy5-labeled probe that are in fluorescence energy transfer when hybridized
      to the same strand internal to an unlabeled primer set. Two hundred and fifty
      samples were genotyped for the C282Y and H63D hemochromatosis causing mutations
      by fluorescent melting curves. Multiplexing was performed by including two primer
      sets and two probe sets in a single tube. In clinically defined groups of 117
      patients and 56 controls, the C282Y mutation was found in 87% (204/234) of
      patient chromosomes, and the relative penetrance of the H63D mutation was 2.4% of
      the homozygous C282Y mutation. Results were confirmed by restriction enzyme
      digestion and agarose gel electrophoresis. In addition, the probe covering the
      H63D mutation unexpectedly identified the A193T polymorphism in some samples.
      This method is amenable to multiplexing and has promise for scanning unknown
      mutations.

PMID- 9777936
TI  - Histopathological evaluation of apoptosis in cancer.

PMID- 9777939
TI  - Beta1C integrin in epithelial cells correlates with a nonproliferative phenotype:
      forced expression of beta1C inhibits prostate epithelial cell proliferation.
AB  - The expression of the beta1C integrin, an alternatively spliced variant of the
      beta1 subunit, was investigated in human adult and fetal tissues. In the adult,
      beta1C immunoreactivity was found in nonproliferative, differentiated simple,
      and/or pseudostratified epithelia in prostate glands and liver bile ducts. In
      contrast, beta1C was undetectable in stratified squamous epithelium of the
      epidermis and/or in hepatocytes. Luminal prostate epithelial cells expressed
      beta1C in vivo and in vitro, but no beta1C was seen in basal cells, which are
      proliferating cells. Fetal prostate expressed beta1C in differentiated glands
      that had a defined lumen, but not in budding glands, indicating that beta1C is a
      marker of prostate epithelium differentiation. The beta1C and the common beta1A
      variants are differentially distributed: beta1A was found in luminal and basal
      epithelial as well as in stromal cells in the prostate. In the liver, beta1C and
      beta1A were coexpressed in biliary epithelium, whereas vascular cells expressed
      only beta1A. Because we found beta1C in nonproliferative and differentiated
      epithelium, we investigated whether beta1C could have a causal role in inhibiting
      epithelial cell proliferation. The results showed that exogenous expression of a
      beta1C, but not of a beta1A, cytoplasmic domain chimeric construct, completely
      inhibited thymidine incorporation in response to serum by prostate cancer
      epithelial cells. Consistent with these in vitro results, beta1C appeared to be
      downregulated in prostate glands that exhibit regenerative features in benign
      hyperplastic epithelium. These data show that the presence of beta1C integrins in
      epithelial cells correlates with a nonproliferative, differentiated phenotype and
      is growth inhibitory to prostate epithelial cells in vitro. These findings
      indicate a novel pathophysiological role for this integrin variant in epithelial
      cell proliferation.

PMID- 9777940
TI  - Typical and atypical carcinoid tumors of the lung are characterized by 11q
      deletions as detected by comparative genomic hybridization.
AB  - Neuroendocrine tumors of the lung represent a wide spectrum of phenotypically
      distinct entities with different biological characteristics such as typical
      carcinoid tumor (TC), atypical carcinoid tumor (AC), large-cell neuroendocrine
      carcinoma (LCNEC), and small-cell lung carcinoma (SCLC). The histogenetic
      relationships between TC, AC, LCNEC, and SCLC are still unclear. This study was
      carried out to provide cytogenetic data about pulmonary neuroendocrine tumors and
      to evaluate their characteristic alterations and histogenetic relations for an
      improved understanding of the mechanisms of tumor development. Twenty-nine
      paraffin-embedded tumor samples of TC (n = 17), AC (n = 6), LCNEC (n = 3), and
      SCLC (n = 3) were selected for isolation of tumor DNA and subsequent comparative
      genomic hybridization (CGH) analysis. To confirm the comparative genomic
      hybridization results for characteristic chromosomal imbalances, selected cases
      were additionally investigated by loss of heterozygosity analysis. For
      statistical evaluation, we also used comparative genomic hybridization data from
      45 published SCLC cases. DNA underrepresentations of 11q were the most frequent
      findings in TC (8 of 17) and AC (4 of 6), whereas these aberrations were rare in
      LCNEC (1 of 3) and SCLC (0 of 3). Furthermore, AC showed DNA underrepresentation
      of 10q (3 of 6) and 13q (3 of 6). In contrast, SCLC and LCNEC were characterized
      by a different pattern of DNA losses (3p-, 4q-, 5q-, 13q-, and 15q-) and gains
      (5p+, 17p+, and +20). Statistical analysis revealed significantly different
      occurrences of 11q deletions in TC/AC versus SCLC (45 published cases of SCLC and
      our 3 cases; P = 0.002; Fisher's exact test). Thus, TC and AC display frequent
      loss of 11q material including the MEN1 gene locus, which represents a
      characteristic genetic alteration in these tumors. Losses of 10q and 13q
      sequences allow a further cytogenetic differentiation between TC and AC. These
      additional changes might be responsible for the more aggressive behavior of AC.
      Three cases of LCNEC, the first to be analyzed by comparative genomic
      hybridization, exhibited similar complex abnormal patterns (4q-, 5q-, 10q-, 13q-,
      15q-) to those of SCLC. Although neuroendocrine tumors of the lung share common
      phenotypic features, suggesting a genotypic relationship, they differ remarkably
      in their cytogenetic characteristics, highlighting an early fundamental molecular
      divergence during the development of these tumors.

PMID- 9777938
TI  - Accumulated clonal genetic alterations in familial and sporadic colorectal
      carcinomas with widespread instability in microsatellite sequences.
AB  - A subset of hereditary and sporadic colorectal carcinomas is defined by
      microsatellite instability (MSI), but the spectra of gene mutations have not been
      characterized extensively. Thirty-nine hereditary nonpolyposis colorectal cancer
      syndrome carcinomas (HNPCCa) and 57 sporadic right-sided colonic carcinomas
      (SRSCCa) were evaluated. Of HNPCCa, 95% (37/39) were MSI-positive as contrasted
      with 31% (18/57) of SRSCCa (P < 0.000001), but instability tended to be more
      widespread in SRSCCa (P = 0.08). Absence of nuclear hMSH2 mismatch repair gene
      product by immunohistochemistry was associated with germline hMSH2 mutation (P =
      0.0007). The prevalence of K-ras proto-oncogene mutations was similar in HNPCCa
      and SRSCCa (30% (11/37) and 30% (16/54)), but no HNPCCa from patients with
      germline hMSH2 mutation had codon 13 mutation (P = 0.02), and two other HNPCCa
      had multiple K-ras mutations attributable to subclones. 18q allelic deletion and
      p53 gene product overexpression were inversely related to MSI (P = 0.0004 and P =
      0.0001, respectively). Frameshift mutation of the transforming growth factor beta
      type II receptor gene was frequent in all MSI-positive cancers (85%, 46/54), but
      mutation of the E2F-4 transcription factor gene was more common in HNPCCa of
      patients with germline hMSH2 mutation than in those with germline bMLH1 mutation
      (100% (8/8) versus 40% (2/5), P = 0.04), and mutation of the Bax proapoptotic
      gene was more frequent in HNPCCa than in MSI-positive SRSCCa (55% (17/31) versus
      13% (2/15), P = 0.01). The most common combination of mutations occurred in only
      23% (8/35) of evaluable MSI-positive cancers. Our findings suggest that the
      accumulation of specific genetic alterations in MSI-positive colorectal cancers
      is markedly heterogeneous, because the occurrence of some mutations (eg, ras, E2F
      4, and Bax genes), but not others (eg, transforming growth factor beta type II
      receptor gene), depends on the underlying basis of the mismatch repair
      deficiency. This genetic heterogeneity may contribute to the heterogeneous
      clinical and pathological features of MSI-positive cancers.

PMID- 9777941
TI  - Angiogenesis in mice with chronic airway inflammation: strain-dependent
      differences.
AB  - Chronic inflammation is associated with blood vessel proliferation and
      enlargement and changes in vessel phenotype. We sought to determine whether these
      changes represent different types of angiogenesis and whether they are stimulus
      dependent. Chronic airway inflammation, produced by infection with Mycoplasma
      pulmonis, was compared in strains of mice known to be resistant (C57BL/6) or
      susceptible (C3H). Tracheal vascularity, assessed in whole mounts after
      Lycopersicon esculentum lectin staining, increased in both strains at 1, 2, 4,
      and 8 weeks after infection, but the type of vascular remodeling was different.
      The number of vessels doubled in tracheas of C57BL/6 mice, with corresponding
      increases of capillaries and venules. In contrast, neither the number nor the
      length of vessels changed in C3H mice. Instead, vessel diameter and endothelial
      cell number doubled, and the proportion of venules doubled with a corresponding
      decrease of capillaries. Although the infection had no effect on baseline plasma
      leakage, in both strains it potentiated the leakage produced by substance P. We
      conclude that the same stimulus can result in blood vessel proliferation or
      enlargement, depending on the host response. Endothelial cells proliferate in
      both cases, but in one case new capillaries form whereas in the other capillaries
      convert to venules.

PMID- 9777942
TI  - Differing patterns of P-selectin expression in lung injury.
AB  - Using two models of acute lung inflammatory injury in rats (intrapulmonary
      deposition of immunoglobulin G immune complexes and systemic activation of
      complement after infusion of purified cobra venom factor), we have analyzed the
      requirements and patterns for upregulation of lung vascular P-selectin. In the
      immune complex model, upregulation of P-selectin was defined by Northern and
      Western blot analysis of lung homogenates, by immunostaining of lung tissue, and
      by vascular fixation of 125I-labeled anti-P-selectin. P-selectin protein was
      detected by 1 hour (long before detection of mRNA) and expression was sustained
      for the next 7 hours, in striking contrast to the pattern of P-selectin
      expression in the cobra venom factor model, in which upregulation was very
      transient (within the 1st hour). In the immune complex model, injury and
      neutrophil accumulation were P-selectin dependent. Upregulation of P-selectin was
      dependent on an intact complement system, and the presence of blood neutrophils
      was susceptible to the antioxidant dimethyl sulfoxide and required C5a but not
      tumor necrosis factor alpha. In contrast, in the cobra venom factor model,
      upregulation of P-selectin, which is C5a dependent, was also dimethyl sulfoxide
      sensitive but neutrophil independent. Different mechanisms that may explain why
      upregulation of lung vascular P-selectin is either transient or sustained are
      discussed.

PMID- 9777944
TI  - Morphometric analysis of lymphatic and blood vessels in human chronic viral liver
      diseases.
AB  - The purpose of this study was to elucidate the morphometric changes occurring in
      hepatic lymphatics in human chronic viral liver diseases and to investigate the
      relationship between liver fibrosis, liver inflammation, and these changes. The
      lymphatic vessels were stained intensely by enzyme histochemistry for 5'
      nucleotidase, whereas blood vessels stained well for alkaline phosphatase. We
      performed a morphometric analysis to estimate the number of lymphatic and blood
      vessels and their areas, using computer graphics software (NIH Image). Both the
      number of lymphatics in the specimens and their areas were increased according to
      the degree of liver fibrosis, but neither showed any relationship with the degree
      of activity of hepatitis. Neither the number nor the areas of the blood vessels
      showed any obvious relationship with the degree of fibrosis or the activity of
      chronic hepatitis. Correlation between clinical and laboratory data and the sizes
      and number of the lymphatics supported these morphological data. Our results
      clarified that the sizes and number of lymphatics are related to the stage of
      fibrosis in chronic viral liver diseases. This is thought to be due to increased
      lymph production, which is caused by the disturbance of the microcirculation
      associated with liver fibrosis.

PMID- 9777943
TI  - Pathogenesis of simian immunodeficiency virus pneumonia: an immunopathological
      response to virus.
AB  - Although many human immunodeficiency virus-infected individuals develop
      lymphocytic interstitial pneumonia, the roles of host and viral factors in the
      pathogenesis of pneumonia are not well defined. Human immunodeficiency virus
      infected children with lymphocytic interstitial pneumonia have human
      immunodeficiency virus-specific cytotoxic T cells in pulmonary infiltrates,
      increased survival time, and a reduced incidence of opportunistic infections,
      suggesting that lymphocytic interstitial pneumonia may reflect an effective
      antiviral immune response. In this study, 20 macaques were inoculated with
      related macrophage-tropic simian immunodeficiency viruses and examined for
      pulmonary lesions and virus gene expression. Ten macaques developed moderate to
      severe pneumonia characterized by perivascular, peribronchial, and interstitial
      infiltrates of lymphocytes and macrophages. Large numbers of pulmonary cytotoxic
      lymphocytes were demonstrated in macaques with moderate to severe pneumonia (P <
      0.05) by immunostaining for TIA-1. There was no difference in viral load between
      macaques with moderate to severe pneumonia and those with mild to no pulmonary
      lesions. In five macaques inoculated with the same virus swarm, there was a
      significant (P < 0.05) inverse correlation between the percentage decline in CD4+
      T-cell counts and the severity of pulmonary lesions. Pulmonary infiltrates of
      cytotoxic lymphocytes, the lack of correlation between severity of pulmonary
      lesions and virus gene expression, and the inverse relationship between pneumonia
      and inmune status suggest that simian immunodeficiency virus pneumonia may
      represent an immunopathological response to macrophage-tropic virus.

PMID- 9777945
TI  - Ontogeny of hepatocyte growth factor (HGF) and its receptor (c-met) in human
      placenta: reduced HGF expression in intrauterine growth restriction.
AB  - Severe intrauterine growth restriction (IUGR) is characterized by abnormal
      placentation. Mouse gene knockout studies show that an absence of either
      hepatocyte growth factor (HGF) or its receptor, c-met, leads to intrauterine
      death secondary to severe IUGR with deficient placentation. In this study,
      immunocytochemistry localized HGF protein throughout placental villi across
      gestation, whereas c-met protein was localized only to the perivillous
      trophoblast and vascular endothelium. Within the IUGR placentae, a reduction in
      HGF immunostaining within the villous stroma was observed. HGF mRNA was strongly
      expressed in the perivascular tissue around the stem villous arteries throughout
      gestation, with weaker expression within the villous stroma and the terminal
      villi. c-met mRNA expression was limited to the perivillous trophoblast,
      particularly in the first trimester, with only a faint hybridization signal from
      the villous stroma. Placental mRNA expression was examined quantitatively using a
      ribonuclease protection assay: HGF and c-met mRNA expression increased from the
      first to the second trimester, reaching a zenith before decreasing again through
      the third trimester to term. HGF mRNA levels were significantly reduced in the
      IUGR placentae (P = 0.036), whereas c-met mRNA expression was within the normal
      range for gestation. These findings suggest that HGF derived from the
      perivascular tissue of stem villous arteries may play an important role in
      controlling normal villous development. Whereas reduced expression of HGF within
      IUGR placentae does not prove a causative link with abnormal villous development,
      the association lends support to this possibility.

PMID- 9777946
TI  - Advanced glycation end products in Alzheimer's disease and other
      neurodegenerative diseases.
AB  - Advanced glycation end products (AGEs) have been implicated in the chronic
      complications of diabetes mellitus and have been reported to play an important
      role in the pathogenesis of Alzheimer's disease. In this study, we examined the
      immunohistochemical localization of AGEs, amyloid beta protein (A beta),
      apolipoprotein E (ApoE), and tau protein in senile plaques, neurofibrillary
      tangles (NFTs), and cerebral amyloid angiopathy (CAA) in Alzheimer's disease and
      other neurodegenerative diseases (progressive supranuclear palsy, Pick's disease,
      and Guamanian amyotrophic lateral sclerosis/Parkinsonism-dementia complex). In
      most senile plaques (including diffuse plaques) and CAA from Alzheimer's brains,
      AGE and ApoE were observed together. However, approximately 5% of plaques were
      AGE positive but A beta negative, and the vessels without CAA often showed AGE
      immunoreactivity. In Alzheimer's disease, AGEs were mainly present in
      intracellular NFTs, whereas ApoE was mainly present in extracellular NFTs. Pick's
      bodies in Pick's disease and granulovacuolar degeneration in various
      neurodegenerative diseases were also AGE positive. In non-Alzheimer
      neurodegenerative diseases, senile plaques and NFTs showed similar findings to
      those in Alzheimer's disease. These results suggest that AGE may contribute to
      eventual neuronal dysfunction and death as an important factor in the progression
      of various neurodegenerative diseases, including Alzheimer's disease.

PMID- 9777947
TI  - Effects of growth factors and basement membrane proteins on the phenotype of U
      373 MG glioblastoma cells as determined by the expression of intermediate
      filament proteins.
AB  - Various growth factors and basement membrane proteins have been implicated in the
      pathobiology of astrocytomas. The goal of this study was to determine the
      relative contribution of these two factors in modulating the phenotype of U-373
      MG glioblastoma cells as determined by the expression of the intermediate
      filament proteins glial fibrillary acidic protein, vimentin, and nestin. For
      these determinations, cells plated in serum-free medium were treated either with
      growth factors binding to tyrosine kinase receptors including transforming growth
      factor-alpha, epidermal growth factor, platelet-derived growth factor-AA, basic
      fibroblast growth factor, and insulin-like growth factor-1 or with basement
      membrane proteins including collagen IV, laminin, and fibronectin. The changes in
      the expression levels of intermediate filament proteins in response to these
      treatments were analyzed by quantitation of immunoblots. The results demonstrate
      that collagen IV and growth factors binding to tyrosine kinase receptors decrease
      the glial fibrillary acidic protein content of U-373 MG cells. Growth factors
      binding to tyrosine kinase receptors also decrease the vimentin content of these
      cells but do not affect their nestin content. On the other hand, basement
      membrane proteins decrease the nestin content of U-373 MG cells but do not affect
      their vimentin content. The significance of these results with respect to the
      role played by different factors in modulating the phenotype of neoplastic
      astrocytes during tumor progression is discussed.

PMID- 9777948
TI  - Characterization of monoclonal antibodies to calpain 3 and protein expression in
      muscle from patients with limb-girdle muscular dystrophy type 2A.
AB  - Monoclonal antibodies were raised to two regions of calpain 3 (muscle-specific
      calcium-activated neutral protease), which is the product of the gene that is
      defective in limb-girdle muscular dystrophy type 2A. The antibodies produced
      characteristic patterns of bands on Western blots: normal calpain 3 protein was
      represented by bands at 94 kd, plus additional fragments at approximately 60 or
      30 kd, according to the antibody used. Specificity was confirmed by the loss of
      all bands in patients with null gene mutations. The "normal" profile of bands was
      observed in muscle from 33 control subjects and 70 disease-control patients.
      Calpain 3 protein was found to be extremely stable in fresh human muscle, with
      full-size protein being detected 8 hours after the muscle had been removed. Blots
      of muscle from nine limb-girdle muscular dystrophy type 2A patients with defined
      mutations showed variation in protein expression, with seven showing a clear
      reduction in the abundance of protein detected. No simple relationship was found
      between the abundance and clinical severity. Two patients showed normal
      expression of the full-size 94 kd band accompanied by a clear reduction in the
      smaller fragments. This pattern was also observed in one patient with an
      undefined form of limb-girdle dystrophy. These results indicate that
      immunodiagnosis is feasible, but caution will need to be exercised with the
      interpretation of near-normal protein profiles.

PMID- 9777949
TI  - Microsatellite instability and mutation of DNA mismatch repair genes in gliomas.
AB  - Microsatellite instability (MSI) has been identified in various human cancers,
      particularly those associated with the hereditary nonpolyposis colorectal cancer
      syndrome. Although gliomas have been reported in a few hereditary nonpolyposis
      colorectal cancer syndrome kindred, data on the incidence of MSI in gliomas are
      conflicting, and the nature of the mismatch repair (MMR) defect is not known. We
      established the incidence of MSI and the underlying MMR gene mutation in 22
      patients ages 45 years or less with sporadic high-grade gliomas (17
      glioblastomas, 3 anaplastic astrocytomas, and 2 mixed gliomas, grade III). Using
      five microsatellite loci, four patients (18%) had high level MSI, with at least
      40% unstable loci. Germline MMR gene mutation was detected in all four patients,
      with inactivation of the second allele of the corresponding MMR gene or loss of
      protein expression in the tumor tissue. Frameshift mutation in the mononucleotide
      tract of insulin-like growth factor type II receptor was found in one high-level
      MSI glioma, but none was found in the transforming growth factor beta type II
      receptor and the Bax genes. There was no family history of cancer in three of the
      patients, and although one patient did have a family history of colorectal
      carcinoma, the case did not satisfy the Amsterdam criteria for hereditary
      nonpolyposis colorectal cancer syndrome. Three patients developed metachronous
      colorectal adenocarcinomas, fitting the criteria of Turcot's syndrome. Thus, MSI
      and germline MMR gene mutation is present in a subset of young glioma patients,
      and these patients and their family members are at risk of developing other
      hereditary nonpolyposis colorectal cancer syndrome-related tumors, in particular
      colorectal carcinomas. These results have important implications in the genetic
      testing and management of young patients with glioma and their families.

PMID- 9777951
TI  - Specific K-ras2 mutations in human sporadic colorectal adenomas are associated
      with DNA near-diploid aneuploidy and inhibition of proliferation.
AB  - Recent studies indicate that p21ras proteins mediate their multiple cell
      functions through interactions with multiple effectors and that the number of new
      effectors is growing. We recently reported that K-ras2 mutations in human
      colorectal adenomas were associated with chromosome instability and proliferation
      changes. In the present study, we extend these previous observations. Hereditary
      and multiple (n > or = 5) adenomas and adenomas with early cancer were excluded.
      Dysplasia was moderate in 91 cases and high in 25, and the median adenoma size
      was 1.5 cm. K-ras2 spectrum analysis was done by sequence-specific
      oligonucleotide hybridization using nuclear suspensions provided by analysis and
      sorting of multiparameter flow cytometry. In particular, tissue inflammatory
      cells were separated for DNA diploid tumors, whereas DNA aneuploid epithelial
      subclones were analyzed separately. K-ras2 mutations and DNA aneuploidy were both
      detected in 29 of 116 (25%) cases. DNA aneuploid index was in the near-diploid
      region in the majority of cases. DNA aneuploidy was strongly associated with G-
      >C/T transversions. An association was also found between low S-phase values and
      G-->A transitions. These findings were confirmed using multivariate logistic
      regression analysis to account for the effects of size, dysplasia, site, type,
      age, and sex. These data suggest that specific K-ras2 mutations in a subgroup of
      human sporadic colorectal adenomas play a role in chromosome instability and,
      contrary to expectations, are associated with inhibition of proliferation.

PMID- 9777950
TI  - Tracing cell fates in human colorectal tumors from somatic microsatellite
      mutations: evidence of adenomas with stem cell architecture.
AB  - Occult aspects of tumor proliferation are likely recorded genetically as their
      microsatellite (MS) loci become polymorphic. However, MS mutations generated by
      division may also be eliminated with death as noncoding MS loci lack selective
      value. Therefore, highly polymorphic MS loci cannot exist unless mutation rates
      are high, or unless mutation losses are inherently minimized. Mutations
      accumulate differently when cell fates are determined intrinsically before or
      extrinsically after division. Stem cell (asymmetrical division as in intestinal
      crypts) and random (asymmetrical and symmetrical division) proliferation,
      respectively, represent simulated cell fates determined before or after division.
      Whereas mutations regardless of selection systematically persist once inherited
      with stem cell proliferation, mutations are eliminated by the symmetrical losses
      of both daughter cells with random proliferation. Therefore, greater genetic
      diversity or MS variance accumulate with stem cell compared with random
      proliferation. MS loci in normal murine intestinal mucosa and xenografts of
      cancer cell lines accumulated mutations, respectively, consistent with stem cell
      and random proliferation. Tumors from patients with hereditary nonpolyposis
      colorectal cancer (HNPCC) demonstrated polymorphic MS loci. Overall, three of
      five adenomas and one of six cancers exhibited high MS variances. Assuming
      mutation rates are not significantly greater in adenomas than in cancers, these
      studies suggest the stem cell proliferation and hierarchy of normal intestines
      persists in many HNPCC adenomas and some cancers. An adenoma stem cell
      architecture can explain the complex polymorphic MS loci observed in HNPCC
      adenomas and account for many adenoma features. In contrast, cancers may lose
      intrinsic control of cell fate. These studies illustrate a feasible phylogenetic
      approach to unravel and describe occult aspects of human tumor proliferation. The
      switch from predominantly stem cell to random proliferation may be a critical and
      defining characteristic of malignancy.

PMID- 9777953
TI  - Multiple intron retention occurs in tumor cell CD44 mRNA processing.
AB  - Markedly increased overall levels of CD44 transcripts and proteins have been
      recognized in many tumors and the inappropriate expression and abnormal assembly
      of the CD44 variable exons has been linked to both tumor growth and metastatic
      potential. We have also previously observed the aberrant inclusion of intron 9 in
      CD44 mRNA transcripts in tumor tissues. In this study we assessed whether such
      retention is specific to certain introns or is a more general phenomenon
      affecting CD44 gene expression in tumor cells. Intron 18 was cloned and sequenced
      from genomic DNA and the novel sequences analyzed and used to create intron 18
      specific probes. The newly characterized intron was found to have consensus 5'
      splice site and branchpoint sequences but a suboptimal 3' splice site. The status
      of CD44 intron 18 retention or excision was assessed in a colon tumor cell line
      (HT29) and in tissue from 20 colorectal tumors and matched normal mucosa. The
      intron was shown to be retained in transcripts from 15 of the 20 (75%) carcinomas
      but in only 3 of the 20 (15%) matched normal samples. These results compare with
      80% retention of CD44 intron 9 in colonic carcinoma tissue mRNA and confirm that
      multiple abnormalities of CD44 mRNA processing occur in tumor cells.

PMID- 9777952
TI  - The clinicopathological features of gastric carcinomas with microsatellite
      instability may be mediated by mutations of different "target genes": a study of
      the TGFbeta RII, IGFII R, and BAX genes.
AB  - Gastric carcinomas with DNA replication errors (RER phenotype) display a
      particular clinicopathologic profile and carry a putative favorable prognosis.
      The RER phenotype has been identified as microsatellite instability in noncoding
      regions, as well as in repeat sequences within exons of several "target genes":
      TGFbeta RII, IGFII R, and BAX. In an attempt to find out whether the RER status
      is a significant prognostic factor in gastric carcinoma in a multivariate
      analysis and whether the clinicopathological features of the RER+ tumors are
      associated with mutations in the "target genes," we evaluated a series of 152
      cases of sporadic gastric carcinoma. Five or six microsatellite loci and/or BAT
      26, a poly(A) tract, were analyzed in each case using polymerase chain reaction
      and electrophoresis. Thirty-five cases (23.0%) were RER+. The RER phenotype was
      closely associated with a low pTNM stage and carried a significantly better
      prognosis. The repeat sequences of the target genes were screened for mutations
      in 28 RER+ and 13 RER-tumors. Mutations in TGFbeta RII occurred in 67.9% of the
      RER+ tumors and were significantly associated with the glandular histotype. IGFII
      R and BAX mutations occurred, respectively, in 25.0% and 32.1% of the cases;
      there was a trend toward an association between mutations in these genes and
      decreased nodal metastization and wall invasiveness, respectively. We conclude
      that the RER status is a significant prognostic indicator in gastric carcinoma
      and that such prognostic influence may be mediated by mutations in TGFbeta RII,
      IGFII R, and BAX genes.

PMID- 9777954
TI  - Human interleukin-10 expression in T/natural killer-cell lymphomas: association
      with anaplastic large cell lymphomas and nasal natural killer-cell lymphomas.
AB  - Several cytokines have been implicated in the pathogenesis of human lymphomas.
      Among them, interleukin-10 (IL-10) is a pleiotropic cytokine with various
      biological effects on B and T lymphocytes. Its expression has been essentially
      studied in B-cell lymphomas, where it appears to act as an autocrine growth
      factor. BCRF1 (also called viral IL-10), an open reading frame of Epstein-Barr
      virus, exhibits extensive sequence and functional homologies with human IL-10.
      Some entities belonging to T- or natural killer (NK)-cell lymphomas are
      characterized by a frequent association with Epstein-Barr virus. We analyzed 39
      cases of peripheral T-cell lymphoma, as well as 7 cases of nasal NK-cell
      lymphoma, for the presence of IL-10 transcripts by in situ hybridization, to see
      whether this cytokine was expressed in these tumors and whether its expression
      could be related to their histological subtype and to the presence of Epstein
      Barr virus. Because the riboprobe used for in situ hybridization recognizes both
      human and viral IL-10, 12 cases were also analyzed by reverse transcription
      polymerase chain reaction to verify the human or viral origin of IL-10. It was
      found that 8 of 11 (73%) anaplastic large cell lymphomas (ALCLs), 2 of 11 (18%)
      pleomorphic T-cell lymphomas, and 3 of 7 (43%) nasal NK-cell lymphomas exhibited
      a large number of IL-10-expressing cells, whereas only rare scattered cells were
      detected in angioimmunoblastic (11 of 11) and in gammadelta T-cell lymphomas (6
      of 6). In ALCLs, the pattern of IL-10 mRNA-expressing cells showed an overlapping
      with the CD30 staining and preferential localization in sinusal and
      perifollicular areas, thereby suggesting that IL-10-expressing cells were tumor
      cells. Furthermore, IL-10 transcripts were detected in the SU-DHL-1 anaplastic
      lymphoma cell line. No correlation with Epstein-Barr virus profile was found,
      because all cases of ALCL were negative for EBER 1 and 2 genes by in situ
      hybridization. We confirmed the presence of human IL-10 mRNA by reverse
      transcription-polymerase chain reaction in ALCLs as well as in NK-cell lymphomas,
      whereas viral IL-10 was not detected. Thus, human and not viral IL-10 is
      frequently expressed by tumor cells in ALCLs and nasal NK-cell lymphomas. In view
      of its function in the proliferation and the differentiation of cytotoxic T and
      NK cells, and its immunosuppressive properties, IL-10 may have a role in the
      pathogenesis of these lymphomas.

PMID- 9777956
TI  - Role of vascular endothelial growth factor in ovarian cancer: inhibition of
      ascites formation by immunoneutralization.
AB  - Ovarian cancer is characterized by the rapid growth of solid intraperitoneal
      tumors and large volumes of ascitic fluid. Vascular endothelial growth factor
      (VEGF) augments tumor growth by inducing neovascularization and may stimulate
      ascites formation by increasing vascular permeability. We examined the role of
      VEGF in ovarian carcinoma using in vivo models in which intraperitoneal or
      subcutaneous tumors were induced in immunodeficient mice using the human ovarian
      carcinoma cell line SKOV-3. After tumor engraftment (7 to 10 days), some mice
      were treated with a function-blocking VEGF antibody (A4.6.1) specific for human
      VEGF. A4.6.1 significantly (P < 0.05) inhibited subcutaneous SKOV-3 tumor growth
      compared with controls. However, tumor growth resumed when A4.6.1 treatment was
      discontinued. In mice bearing intraperitoneal tumors (IP mice), ascites
      production and intraperitoneal carcinomatosis were detected 3 to 7 weeks after
      SKOV-3 inoculation. Importantly, A4.6.1 completely inhibited ascites production
      in IP mice, although it only partially inhibited intraperitoneal tumor growth.
      Tumor burden was variable in A4.6.1-treated IP mice; some had minimal tumor,
      whereas in others tumor burden was similar to that of controls. When A4.6.1
      treatment was stopped, IP mice rapidly (within 2 weeks) developed ascites and
      became cachectic. These data suggest that in ovarian cancer, tumor-derived VEGF
      is obligatory for ascites formation but not for intraperitoneal tumor growth.
      Neutralization of VEGF activity may have clinical application in inhibiting
      malignant ascites formation in ovarian cancer.

PMID- 9777955
TI  - Host microvasculature influence on tumor vascular morphology and endothelial gene
      expression.
AB  - We have previously demonstrated that vascular endothelial growth factor-165
      (VEGF), a tumor-secreted angiogenic factor, can acutely and chronically induce
      fenestrations in microvascular endothelium (Cancer Res 1997, 57:765-772). Because
      the morphology and function of microvascular endothelium differs from tissue to
      tissue, we undertook studies to examine whether the neovasculature in tumors also
      differed depending upon tumor location. Four tumor types implanted in the brain
      or subcutis in nude mice were studied: a murine rhabdomyosarcoma (M1S), a murine
      mammary carcinoma (EMT), and two human glioblastomas (U87 and U251). In addition,
      we studied Chinese hamster ovary cells stably transfected with human VEGF165. As
      previously reported, tumors grown in the subcutaneous space had a
      microvasculature that was fenestrated and had open endothelial gaps. The
      identical tumors when grown in the brain also had fenestrated endothelium and
      vessels with open endothelial gaps, but they were drastically reduced in
      occurrence. Open endothelial gaps were not seen in all tumors implanted in the
      brain (EMT and M1S), although fenestrated endothelium was always seen. VEGF and
      VEGF receptors were measured in tumors from both locations by immunoblotting and
      competitive polymerase chain reaction, respectively. VEGF amount was not
      significantly different between the tumor locations. Interestingly, total tumor
      vascular mRNA expression of both Flk-1 and Flt-1 was greater in tumor vessels
      derived from the brain compared with tumor vessels derived from subcutaneous
      tissues. These results demonstrate that the host microvascular environment
      determines the morphology and function of the tumor vasculature and that
      endothelia from different tissues vary in their ability to express the VEGF
      receptors given identical stimuli.

PMID- 9777957
TI  - Modulation of endothelial cell function by normal polyspecific human intravenous
      immunoglobulins: a possible mechanism of action in vascular diseases.
AB  - Intravenous immunoglobulin (IVIg) is increasingly used in the treatment of
      autoimmune and inflammatory diseases, including vasculitides and Kawasaki
      disease. However, the outcome of IVIg interaction with endothelial cells of the
      vascular bed is not clear as yet. We have investigated the effect of IVIg on the
      in vitro activation of human endothelial cells, as assessed by cell proliferation
      and reverse transcription-polymerase chain reaction-detected expression of mRNA
      coding for adhesion molecules (intercellular adhesion molecule-1 and vascular
      cellular adhesion molecule-1), chemokines (monocyte chemoattractant protein-1,
      macrophage colony-stimulating factor, and granulocyte-macrophage colony
      stimulating factor), and proinflammatory cytokines (tumor necrosis factor-alpha,
      interleukin-1beta, and interleukin-6). IVIg inhibited proliferation of
      endothelial cells in a time-dependent manner. This effect was dependent on both
      Fc and F(ab')2 fragments of the immunoglobulin molecule and was fully reversible.
      Tumor necrosis factor-alpha and interleukin-1beta also inhibited thymidine
      incorporation, but to a lesser degree. IVIg had no effect on basal levels of mRNA
      coding for the adhesion molecules, chemokines, and proinflammatory cytokines.
      IVIg fully down-regulated the expression induced by tumor necrosis factor-alpha
      or interleukin-1beta of mRNA coding for these molecules. Thus, blockade of
      cellular proliferation and of cytokine-induced expression of adhesion molecules,
      chemokines, and cytokines may explain the therapeutic effect of IVIg in vascular
      and inflammatory disorders.

PMID- 9777959
TI  - Detection of human endogenous retrovirus type K-specific transcripts in
      testicular parenchyma and testicular germ cell tumors of adolescents and adults:
      clinical and biological implications.
AB  - Testicular germ cell tumors (TGCTs) of adolescents and adults have been shown to
      contain proteins of the human endogenous retrovirus type K family. In a recent
      study, expression of these retroviral sequences was confirmed using in situ
      hybridization, which also showed expression in carcinoma in situ, the precursor
      of all TGCTs. Because of the clinical significance of a test for early diagnosis
      of TGCTs, we studied whether expression of human endogenous retrovirus type K
      genes could be an informative parameter. Therefore, we investigated TGCTs of
      various histologies and testicular parenchyma with and without carcinoma in situ
      using reverse transcription-polymerase chain reaction for expression of the gag,
      env, and prt genes. The gag and prt genes were expressed in all samples tested.
      The env transcripts were not found in TGCTs showing somatic differentiation only
      but could be detected in most normal testicular parenchyma samples. Therefore,
      detection of human endogenous retrovirus type K transcripts cannot be used for
      early diagnosis of TGCTs. Simultaneous expression of multiple gag sequences was
      found both in normal parenchyma and TGCTs, and we demonstrated that expression of
      gag sequences with an extra G, necessary to generate a functional protein, was
      not limited to TGCTs.

PMID- 9777958
TI  - Bikunin present in human peritoneal fluid is in part derived from the interaction
      of serum with peritoneal mesothelial cells.
AB  - We recently reported that peritoneal fluid mainly contains two proteoglycans; one
      is the interstitial proteoglycan referred to as decorin, and the other an
      uncharacterized small chondroitin sulfate proteoglycan. In the present study, we
      have used a two-step process to isolate the small chondroitin sulfate
      proteoglycan free of decorin. The purified molecule ran as a single band on
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis with apparent molecular
      mass 50 kd made up of a chondroitin-4-sulfate glycosaminoglycan chain and a 30-kd
      core protein. NH2-terminal analysis of the core protein showed significant
      sequence homology with bikunin, a component of the human inter-alpha-trypsin
      inhibitor (IalphaI) family. A Western blot analysis using anti-human inter-alpha
      trypsin inhibitor confirmed the identity of the small chondroitin sulfate
      proteoglycan as bikunin, and a trypsin inhibitor counterstain assay confirmed its
      anti-trypsin activity. Examination of serum from patients receiving continuous
      peritoneal dialysis suggests that free bikunin in peritoneal fluid may be the
      result of leakage of serum proteins into the peritoneum. Our findings further
      show that the interaction of serum with peritoneal mesothelial cells offers a new
      and novel explanation for the presence of bikunin in peritoneal fluid.

PMID- 9777960
TI  - Induction of arthritis in BALB/c mice by cartilage link protein: involvement of
      distinct regions recognized by T and B lymphocytes.
AB  - Both type II collagen and the proteoglycan aggrecan are capable of inducing an
      erosive inflammatory polyarthritis in mice. In this study we provide the first
      demonstration that link protein (LP), purified from bovine cartilage, can produce
      a persistent, erosive, inflammatory polyarthritis when injected repeatedly
      intraperitoneally into BALB/c mice. We discovered a single T-cell epitope,
      located within residues 266 to 290 of bovine LP (NDGAQIAKVGQIFAAWKLLGYDRCD),
      which is recognized by bovine LP-specific T lymphocytes. We also identified three
      immunogenic regions in bovine LP that contain epitopes recognized by antibodies
      in hyperimmunized sera. One of these B-cell regions is found in the most species
      variable domain of LP (residues 1 to 36), whereas the other epitopes are located
      in the most conserved regions (residues 186 to 230 and 286 to 310). The latter
      two regions contain an AGWLSDGSVQYP motif shared by the G1 globulin domain of
      aggrecan core protein, versican, neurocan, glial hyaluronan-binding protein, and
      the hyaluronan receptor CD44. Our data reveal that the induction of arthritis is
      associated with antibody reactivities to B-cell epitopes located at residues 1 to
      19. Together, these observations show that another cartilage protein, LP, like
      type II collagen and the proteoglycan aggrecan, is capable of inducing an erosive
      inflammatory arthritis in mice and that the immunity to LP involves recognition
      of both T- and B-cell epitopes. This immunity may be of importance in the
      pathogenesis of inflammatory joint diseases, such as juvenile rheumatoid
      arthritis, in which cellular immunity to LP has been demonstrated.

PMID- 9777961
TI  - Progressive neurodegeneration in aspartylglycosaminuria mice.
AB  - Aspartylglycosaminuria (AGU) is one of the most common lysosomal storage
      disorders in humans. A mouse model for AGU has been recently generated through
      targeted disruption of the glycosylasparaginase gene, and at a young age the
      glycosyl asparaginase-deficient mice demonstrated many pathological changes found
      in human AGU patients (Kaartinen V, Mononen I, Voncken J-W, Gonzalez-Gomez I,
      Heisterkamp N, Groffen J: A mouse model for aspartylglycosaminuria. Nat Med 1996,
      2:1375-1378). Our current findings demonstrate that after the age of 10 months,
      the general condition of null mutant mice gradually deteriorated. They suffered
      from a progressive motoric impairment and impaired bladder function and died
      prematurely. A widespread lysosomal hypertrophy in the central nervous system was
      detected. This neuronal vacuolation was particularly severe in the lateral
      thalamic nuclei, medullary reticular nuclei, vestibular nuclei, inferior olivary
      complex, and deep cerebellar nuclei. The oldest animals (20 months old) displayed
      a clear neuronal loss and gliosis, particularly in those regions, where the most
      severe vacuolation was found. The severe ataxic gait of the older mice was likely
      due to the dramatic loss of Purkinje cells, intensive astrogliosis and
      vacuolation of neurons in the deep cerebellar nuclei, and the severe vacuolation
      of the cells in vestibular and cochlear nuclei. The impaired bladder function and
      subsequent hydronephrosis were secondary to involvement of the central nervous
      system. These findings demonstrate that the glycosylasparaginase-deficient mice
      share many neuropathological features with human AGU patients, providing a
      suitable animal model to test therapeutic strategies in the treatment of the
      central nervous system effects in AGU.

PMID- 9777963
TI  - Spontaneous autoimmune gastritis in C3H/He mice: a new mouse model for gastric
      autoimmunity.
AB  - Autoimmune gastritis is the underlying pathological lesion of pernicious anemia
      in humans. The lesion is characterized by a chronic inflammatory infiltrate in
      the gastric mucosa with loss of parietal and zymogenic cells. It is associated
      with circulating autoantibodies to the gastric H/K-ATPase, the enzyme responsible
      for acidification of gastric juice. Experimental models of autoimmune gastritis
      have previously been produced in mice after a variety of manipulations, including
      thymectomy. Here we report for the first time a spontaneous mouse model of
      autoimmune gastritis in C3H/He mice. The spontaneous gastritis is also
      accompanied by circulating autoantibodies to the gastric H/K-ATPase. The
      spontaneous mouse model should be useful for studies directed toward the
      immunopathogenesis and treatment of autoimmune gastritis.

PMID- 9777962
TI  - Mouse model of venous bypass graft arteriosclerosis.
AB  - Saphenous vein grafts are widely used for treatment of severe atherosclerosis via
      aortocoronary bypass surgery, a procedure often complicated by later occlusion of
      the graft vessel. Because the molecular mechanisms of this process remain largely
      unknown, quantitative models of venous bypass graft arteriosclerosis in
      transgenic mice could be useful to study this process at the genetic level. We
      describe herein a new model of vein grafts in the mouse that allows us to take
      advantage of transgenic, knockout, or mutant animals. Autologous or isogeneic
      vessels of the external jugular or vena cava veins were end-to-end grafted into
      carotid arteries of C57BL/6J mice. Vessel wall thickening was observed as early
      as 1 week after surgery and progressed to 4-, 10-, 15-, and 18-fold original
      thickness in grafted veins at age 2, 4, 8, and 16 weeks, respectively. The lumen
      of grafted veins was significantly narrowed because of neointima hyperplasia.
      Histological and immunohistochemical analyses revealed three lesion processes:
      marked loss of smooth muscle cells in vein segments 1 and 2 weeks after grafting,
      massive infiltration of mononuclear cells (CD11b/18+) in the vessel wall between
      2 and 4 weeks, and a significant proliferation of vascular smooth muscle cells
      (alpha-actin+) to constitute neointimal lesions between 4 and 16 weeks. Similar
      vein graft lesions were obtained when external jugular veins or vena cava were
      isografted into carotid arteries of C57BL/6J mice. Moreover, no significant
      intima hyperplasia in vein-to-vein isografts was found, although there was
      leukocyte infiltration in the vessel wall. Thus, this model, which reproduces
      many of the features of human vein graft arteriosclerosis, should prove useful
      for our understanding of the mechanism of vein graft disease and to evaluate the
      effects of drugs and gene therapy on vascular diseases.

PMID- 9777965
TI  - Rate of apoptosis in human atherosclerosis.

PMID- 9777964
TI  - Atherosclerosis is the leading cause of death in the developed societies.

PMID- 9777966
TI  - Introduction to care of chronic wounds.

PMID- 9777967
TI  - The burden of diabetic foot ulcers.
AB  - Lower extremity ulcers represent a major concern for patients with diabetes and
      for those who treat them, from both a quality of life and an economic standpoint.
      Studies to evaluate quality of life have shown that patients with foot ulcers
      have decreased physical, emotional, and social function. Analyses of economic
      impact have shown (1) the majority of costs occur in the inpatient setting, (2) a
      lack of financial benefit when comparing primary amputation with an aggressive
      approach to limb salvaging including vascular reconstruction, and (3) private
      insurance provides greater reimbursement for inpatient care than does Medicare.
      Results of etiologic studies suggest that hyperglycemia induces diabetes-related
      complications through sorbitol accumulation and protein glycation, and the
      resultant nerve damage manifests as peripheral neuropathy, which predisposes to
      ulcer development. Patients with diabetes also have an increased incidence of
      peripheral vascular disease, impaired wound healing, and decreased ability to
      fight infection. In light of these factors, it is sometimes difficult to
      determine the optimal course for patient management. This review is aimed at
      helping healthcare providers make better decisions about treatment, resource use,
      and strategies for future foot ulcer prevention.

PMID- 9777968
TI  - The development and complications of diabetic foot ulcers.
AB  - Neuropathy and ischemia, two common complications of diabetes mellitus, are the
      primary underlying risk factors for the development of foot ulcers and their
      complications. The presence of symmetric distal polyneuropathy, encompassing
      motor, sensory, and autonomic involvement, is one of the most important factors
      in the development of diabetic foot ulcers. Perhaps one third of diabetic foot
      ulcers have a mixed neuropathic and ischemic etiology. Although neuropathy and
      ischemia are the primary predisposing factors in the formation of diabetic foot
      ulcers, an initiating factor, such as physical or mechanical stress, is required
      for an ulcer to develop. Ischemic ulcers develop as a result of low perfusion
      pressure in a foot with inadequate blood supply, whereas neuropathic ulcers
      result from higher pressures in a foot with adequate blood supply but loss of
      protective sensation. In addition to increasing the risk of ulceration, diabetes
      mellitus also increases the risk of infection by impairing the body's ability to
      eliminate bacteria. The processes by which ulcers develop are reviewed here.

PMID- 9777969
TI  - Foundations of good ulcer care.
AB  - Diabetic foot ulcers are a significant healthcare problem affecting more than 1
      million patients at some point in their lifetime. Good ulcer care begins with
      thorough assessment of the ulcer, which includes determining whether the ulcer is
      infected and whether neuropathy or peripheral vascular disease is present. The
      principles of good wound care include use of proper footwear, non-weight-bearing
      limb support, use of appropriate antibiotics, debridement, aggressive
      revascularization, control of serum glucose levels, and careful monitoring of the
      ulcer. For refractory ulcers, new therapies, such as the use of exogenous
      recombinant growth factors, are being developed that may have a significant
      benefit in treating these ulcers and lowering the amputation rate.

PMID- 9777970
TI  - Physiology and healing dynamics of chronic cutaneous wounds.
AB  - In the last few decades, a great deal of progress has been made in understanding
      the cellular and biochemical interplay that comprises the normal wound healing
      response. This response is a complex process involving intricate interactions
      among a variety of different cell types, structural proteins, growth factors, and
      proteinases. The normal wound repair process consists of three phases-
      inflammation, proliferation, and remodeling--that occur in a predictable sequence
      and comprise a series of cellular and biochemical events. A review of the
      biochemical and physiologic processes that regulate wound healing and the cascade
      of cellular events that gives rise to the healing process is presented here.

PMID- 9777971
TI  - Impediments to wound healing.
AB  - Chronic wounds will often heal in a short period of time if factors that inhibit
      wound healing are identified and managed. Recombinant growth factor therapy may
      provide an added stimulus to healing in certain types of chronic wounds. However,
      there remains no substitute for a physiologic environment conducive to tissue
      repair and regeneration, without which the efficacy of growth factor therapy is
      questionable. Some of the most commonly encountered and clinically significant
      impediments to wound healing include wound hypoxia, infection, presence of debris
      and necrotic tissue, use of anti-inflammatory medications, a diet deficient in
      vitamins or minerals, or general nutritional deficiencies, tumors, environmental
      factors, and metabolic disorders, such as diabetes mellitus. Treatment of chronic
      wounds should be directed against the main etiologic factors responsible for the
      wound. Moreover, factors that may impede healing must be identified and, if
      possible, corrected, for healing to occur.

PMID- 9777972
TI  - Preclinical promise of becaplermin (rhPDGF-BB) in wound healing.
AB  - Advances in molecular biology have made possible the production of highly
      purified recombinant human proteins, and recombinant human growth factors have
      emerged as potential therapeutic wound healing agents. Becaplermin (recombinant
      human platelet-derived growth factor-BB [rhPDGF-BB]) quickly emerged as one of
      the leading candidates for clinical trials. Before the expected therapeutic
      potential of rhPDGF-BB and other growth factors could be realized, a number of
      concerns had to be addressed (eg, would growth factors show effects in normal
      animals, what parameters of wound healing would be affected, and would quality of
      healed wounds be normal?). In animal models, rhPDGF-BB demonstrated wound healing
      activity, predominantly by enhancing the formation of granulation tissue, but it
      was not known whether this effect on granulation tissue would translate into
      enhanced healing of chronic skin ulcers in humans. The objective of this article
      is to review how the study of rhPDGF-BB in animal wound healing models has
      assisted in addressing the potential clinical utility of rhPDGF-BB. Results of
      animal studies are summarized, and the advantages and limitations of the animal
      models are discussed.

PMID- 9777973
TI  - A review of nonclinical toxicology studies of becaplermin (rhPDGF-BB).
AB  - Becaplermin (recombinant human platelet-derived growth factor-BB [BB homodimer,
      rhPDGF-BB]) has demonstrated a favorable safety profile in a series of
      nonclinical studies designed to assess its systemic toxicity, sensitization,
      local irritation, and genotoxic potential. No significant local or systemic
      toxicity directly attributable to becaplermin was observed following single and
      multiple intravenous or subcutaneous administration at doses up to 3 mg/kg in
      monkeys. Administration of single large intravenous doses (up to 100 mg/kg) and
      repeated dosing at 1 or 3 mg/kg in mice resulted in rapidly reversible
      vasodilation and central nervous system depression. In a bone-toxicity study,
      becaplermin produced histomorphologic changes suggestive of accelerated bone
      remodeling, which were judged to be potentially reversible. Similar findings have
      not been observed in humans. Although becaplermin was not considered a dermal or
      ocular irritant, some skin-sensitizing effects were observed in animals; this
      finding was not unexpected for a recombinant human-derived protein. Becaplermin
      was not genotoxic in a variety of in vitro assays and in one in vivo assay.

PMID- 9777974
TI  - Effects of chronic wound fluid on the structure and biological activity of
      becaplermin (rhPDGF-BB) and becaplermin gel.
AB  - In this study, the effects of chronic wound fluid on the structure and biological
      activity of becaplermin (recombinant human platelet-derived growth factor-BB
      [rhPDGF-BB]) were evaluated. Wound fluid was collected from 12 subjects with
      diabetic ulcers or pressure ulcers. Wound fluid +/- becaplermin was added to cell
      cultures before- and after incubation for 12 hours at 37 degrees C or after 12
      hours' topical treatment. Biological activity, concentration, and immunogenicity
      were determined by [3H]thymidine incorporation into quiescent human foreskin
      fibroblasts, enzyme-linked immunosorbent assay (ELISA), and Western blot
      analysis, respectively. No PDGF-BB or mitogenic activity was detected in chronic
      wound fluid alone. Mitogenic activity was present in post-treatment samples from
      becaplermin-treated subjects but not placebo-treated subjects. Exposure to
      chronic wound fluid for 12 hours did not alter the amount, banding pattern, or
      mitogenic activity of becaplermin. Biologically active becaplermin remains in
      wound fluid 12 hours after topical application of becaplermin gel.

PMID- 9777975
TI  - Clinical safety of becaplermin (rhPDGF-BB) gel. Becaplermin Studies Group.
AB  - This overview of the safety of becaplermin gel is based on six well-controlled
      clinical studies that included patients with lower extremity diabetic neuropathic
      ulcers. Patients receiving becaplermin gel (n = 538), placebo gel (n = 278), or
      good ulcer care alone (n = 190) had a similar incidence of ulcer-related adverse
      events, such as infection, cellulitis, or osteomyelitis. Erythematous rash
      occurred in 2% of patients with suspected wound infections treated with
      becaplermin gel and 1% of patients treated with placebo gel. No rashes were
      observed in patients treated with good ulcer care alone. The incidence of
      cardiovascular, respiratory, musculoskeletal, and central and peripheral nervous
      system disorders were similar across all treatment groups. Mortality rates were
      also similar across all treatment groups. Patients treated with becaplermin gel
      did not develop neutralizing antibodies against becaplermin. Therefore,
      becaplermin gel appears to be a safe therapy for the treatment of lower extremity
      diabetic ulcers.

PMID- 9777977
TI  - The future of recombinant growth factors in wound healing.
AB  - For more than a decade, clinical trials have been conducted of the application of
      topical exogenous recombinant growth factors in attempts to accelerate the
      healing of chronic wounds. Although the results of some of these trials have been
      encouraging, overall the results have been somewhat discouraging. Much of the
      difficulty lies in the paucity of carefully controlled clinical trials of wound
      healing. Since wound healing is a complex process that can be influenced, both
      positively and negatively, by many factors, designing these trials has proved
      difficult. To date, only a single recombinant growth factor-recombinant human
      platelet-derived growth factor-BB (rhPDGF-BB)- has been approved by the US Food
      and Drug Administration; and that only for use in diabetic foot ulcers. It is
      unlikely, however, that a single growth factor will be able to resolve all issues
      of repair or strengthen all vulnerabilities of chronic wounds. Our expectation,
      therefore, is that growth factors, cytokines, and other biologic agents will be
      used more specifically in the future, for example, by targeting growth factor
      therapy at those specific components or processes that a given wound uses to
      heal.

PMID- 9777978
TI  - The pathologist as optimist: cancer grade deflation in prostatic needle biopsies.

PMID- 9777976
TI  - Clinical efficacy of becaplermin (rhPDGF-BB) gel. Becaplermin Gel Studies Group.
AB  - The results of four multicenter, randomized, placebo-controlled, parallel group
      studies of the efficacy of becaplermin gel are reviewed here. The four studies
      included a total of 922 patients, all of whom received a standardized regimen of
      good ulcer care. Patients were randomized to receive placebo gel, 30 or 100
      microg/g becaplermin gel, or good ulcer care alone. In Studies 1 and 2, the
      incidence of complete healing was significantly higher in patients receiving
      becaplermin gel (30 microg/g, Study 1; 100 microg/g, Study 2) compared with that
      in patients receiving placebo gel. In Study 3, which was not powered for
      statistical analysis, the incidence of complete healing in patients treated with
      100 microg/g becaplermin gel was approximately twice that of patients treated
      with good ulcer care alone. In Study 4, there was no significant difference in
      the incidence of complete healing in patients treated with becaplermin gel versus
      good ulcer care alone.

PMID- 9777979
TI  - Papillary glioneuronal tumor: a new variant of mixed neuronal-glial neoplasm.
AB  - We describe the clinicopathologic features of nine cases of a unique papillary
      glioneuronal tumor (PGNT) exhibiting astrocytic as well as extensive and varied
      neuronal differentiation. The four male and five female patients studied ranged
      in age from 11 to 52 years (mean 27.7 years). They either presented with mild
      neurologic symptoms or were asymptomatic. Magnetic resonance imaging showed
      demarcated cystic, 1.5-cm to 7-cm contrast-enhancing masses; five involved the
      temporal lobe, two the parietal, and two the frontal. All but one were totally
      resected. No recurrence was noted despite a follow-up period of 3 years. Two
      microscopic components were evident: 1) compact pseudopapillae composed of
      hyalinized vessels covered by a single layer of glial fibrillary acid protein
      (GFAP)-positive astrocytes and 2) synaptophysin-positive neuronal cells of
      varying size, including neurocytes, ganglioid cells, and ganglion cells within
      neuropil. Immunostains for chromogranin-A were negative, as was in situ
      hybridization for chromogranin-A mRNA. Ultrastructurally, neuronal cells featured
      microtubule-containing processes and aberrant synaptic terminals, but dense core
      granules were rare. Overall, cellularity was moderate and atypia was minimal. No
      mitotic activity or necrosis was noted. The proportions of the two components
      varied, but essential morphologic findings were identical in all cases. In that
      the clinical, radiographic, and morphologic characteristics of PGNT are
      distinctive, it appears to represent a previously undescribed form of mixed
      neuronal-glial tumor of the central nervous system.

PMID- 9777980
TI  - Differential diagnosis between classic Hodgkin's lymphoma, T-cell-rich B-cell
      lymphoma, and paragranuloma by paraffin immunohistochemistry.
AB  - There are significant difficulties in the differential diagnosis of lymphomas at
      the interface between classic Hodgkin's lymphoma and both paragranuloma and T
      cell-rich B-cell lymphoma as well as at the interface between T-cell-rich B-cell
      lymphoma and paragranuloma. We therefore investigated 197 cases (155 classic
      Hodgkin's lymphomas, 32 T-cell-rich B-cell lymphomas, and 10 paragranulomas) by
      paraffin immunohistochemistry. Special interest was given to cases with a B-cell
      phenotype of tumor cells. The reactive inflammatory infiltrate in both classic
      Hodgkin's lymphoma and T-cell-rich B-cell lymphoma was rich in TIA-1-positive
      cytolytic lymphocytes, and CD57-positive cells were rarely encountered. In
      contrast, in paragranuloma CD57-positive cells and small B-lymphocytes
      predominated the background infiltrate. The tumor cells in cases of classic
      Hodgkin's lymphoma were positive for CD30 in 95%, for CD15 in 75%, and for CD20
      in 22%. Apart from this, vimentin was expressed in >95% of the cases. All cases
      of T-cell-rich B-cell lymphoma were negative for vimentin, CD30, and CD15. The
      reactivity of the tumor cells for CD30, CD15, CD20, and vimentin together with
      the background reactivity for CD57 and TIA-1 seem to reliably discriminate
      between the entities and should therefore help to increase the interobserver
      reproducibility of diagnoses in the gray zone around Hodgkin's lymphoma.

PMID- 9777982
TI  - Role of immunohistochemistry in distinguishing epithelial peritoneal
      mesotheliomas from peritoneal and ovarian serous carcinomas.
AB  - The histologic distinction between epithelial peritoneal mesothelioma and
      papillary serous carcinoma diffusely involving the peritoneum may be difficult.
      Although some investigators have indicated that immunohistochemistry can
      facilitate this differential diagnosis. only a few studies using a limited number
      of markers have been published. In this study, the immunoreactivity of keratin
      5/6, vimentin, epithelial membrane antigen, thrombomodulin, calretinin, MOC-31,
      Ber-EP4, carcinoembryonic antigen, TAG-72 (B72.3), CD15 (Leu-M1), placental
      alkaline phosphatase, CA19-9, CA-125, HBME-1, 44-3A6, and S-100 protein was
      investigated in 35 epithelial peritoneal mesotheliomas, and 45 papillary serous
      carcinomas [30 ovarian (10 primary and 20 metastatic to the peritoneum) and 15
      papillary serous carcinomas of the peritoneum]. After analyzing the results, it
      is concluded that calretinin, thrombomodulin, and keratin 5/6 are the best
      positive markers for differentiating epithelial malignant mesotheliomas from
      papillary serous carcinomas diffusely involving the peritoneum. The best
      diagnostic discriminators among the antibodies considered to be negative markers
      for mesothelioma are MOC-31, B72.3, Ber-EP4, CA19-9, and Leu-M1. Immunostaining
      for carcinoembryonic antigen, placental alkaline phosphatase, epithelial membrane
      antigen, vimentin, HBME-1, 44-3A6, CA-125, or S-100 have little or no diagnostic
      utility in establishing the differential diagnosis between these conditions. The
      results of this study also confirm previous observations indicating that both
      papillary serous carcinomas of the peritoneum and serous carcinomas of the ovary
      have a similar phenotype and, therefore, immunohistochemical studies are not
      useful in separating these entities.

PMID- 9777981
TI  - Statistical evaluation of diagnostic and prognostic features of CD30+ cutaneous
      lymphoproliferative disorders: a clinicopathologic study of 65 cases.
AB  - Several clinical and histopathologic features of 65 CD30+ cutaneous
      lymphoproliferations were evaluated for their diagnostic value between CD30+
      primary versus secondary cutaneous lymphomas and for their prognostic
      significance. Primary cutaneous disease, spontaneous regression, and absence of
      extracutaneous spreading (but not age < or =60 years) were associated with a
      better prognosis. Epithelial membrane antigen, BNH9, CD15 or CBF.78 antigen were
      expressed in all types of cutaneous lymphoproliferations. However, epithelial
      membrane antigen immunoreactivity was more frequently expressed in CD30+
      secondary cutaneous large-cell lymphoma. Among CD30+ primary cutaneous large-cell
      lymphoma, CD15 expression was only seen in localized skin lesions. P53 expression
      was not associated with spontaneous regression, extracutaneous spreading, or
      survival. Nested reverse transcriptase-polymerase chain reaction allowed the
      detection of NPM-ALK transcripts in 10 of 26 CD30+ primary and in 3 of 11
      secondary cutaneous large-cell lymphomas. The ALK protein was detected in only 1
      of 50 primary and in 4 of 15 secondary cutaneous CD30+ lymphoproliferations. In
      CD30+ primary cutaneous lymphoproliferation, NPM-ALK transcripts might be
      expressed by very rare normal or tumoral cells that are undetectable by
      immunohistochemistry. However, the expression of either NPM-ALK transcripts or
      ALK-protein was not correlated with prognosis or age in CD30+ cutaneous
      lymphoproliferations.

PMID- 9777983
TI  - Value of cytokeratin 5/6 immunostaining in distinguishing epithelial mesothelioma
      of the pleura from lung adenocarcinoma.
AB  - The immunohistochemical diagnosis of mesothelioma is commonly made by using a
      battery of antibodies that reacts with lung adenocarcinomas but not with
      epithelial mesotheliomas. Only recently have markers that are often expressed in
      mesotheliomas but not in adenocarcinomas been recognized. Some of these markers,
      however, require frozen tissue sections, whereas others are not commercially
      available, or their value remains controversial. In a recent publication, it was
      suggested that immunostaining for cytokeratin 5/6 could assist in distinguishing
      epithelial mesothelioma from lung adenocarcinoma. To determine the practical
      value of cytokeratin 5/6 immunostaining in the diagnosis of mesothelioma, 40
      formalin-fixed, paraffin-embedded epithelial pleural mesotheliomas, 30 pulmonary
      adenocarcinomas, 93 nonpulmonary adenocarcinomas, 15 squamous carcinomas of the
      lung, 5 large cell undifferentiated carcinomas of the lung, and 12 metastatic
      transitional cell carcinomas to the lung were stained with the same antibody,
      which was obtained from a commercial source. Cytokeratin 5/6 reactivity was
      observed in all 40 mesotheliomas, but there was none in any of the 30 pulmonary
      adenocarcinomas. Focal or weak reactivity was observed in 14 of 93 nonpulmonary
      adenocarcinomas (10 of 30 ovarian, 2 of 10 endometrial, 1 of 18 breast, I of 7
      thyroid, 0 of 10 kidney, 0 of 10 colonic, and 0 of 8 prostatic). All 15 squamous
      carcinomas of the lung, 6 of 12 transitional cell carcinomas metastatic to the
      lung, and 3 of 5 large cell undifferentiated carcinomas of the lung expressed
      cytokeratin 5/6. It is concluded that cytokeratin 5/6 immunostaining is not only
      useful in separating epithelial pleural mesotheliomas from pulmonary
      adenocarcinomas but also can assist in distinguishing epithelial mesotheliomas
      from nonpulmonary adenocarcinomas metastatic to the pleura.

PMID- 9777984
TI  - Intramuscular myxoma: a clinicopathologic study of 51 cases with emphasis on
      hypercellular and hypervascular variants.
AB  - Intramuscular myxoma (IM) is a benign soft-tissue tumor that presents as a deeply
      seated mass confined to skeletal muscle. Surgical excision is virtually always
      curative. Recurrence, even after incomplete resection, is exceptional.
      Intramuscular myxoma is classically described as hypocellular and hypovascular,
      and is composed of cytologically bland stellate and bipolar fibroblasts separated
      by abundant extracellular myxoid matrix. What is underemphasized, however, is
      that IMs often show areas of increased cellularity and vascularity that can lead
      to a mistaken diagnosis of sarcoma, especially myxofibrosarcoma, low-grade
      fibromyxoid sarcoma, and myxoid liposarcoma. In this report, we describe the
      clinicopathologic features of 51 IMs with special emphasis on those that exhibit
      these "hypercellular regions." The patients included 35 women and 16 men who
      ranged in age from 27 to 89 (mean 52) years. The tumors measured from 2 to 15
      (average 5.6) cm and all had a gelatinous, lobulated cut surface. Histologically,
      they all demonstrated classic hypocellular, hypovascular regions. Thirty-eight
      tumors contained areas of relative increased cellularity that occupied from 10 to
      80% of the tumor. These foci had increased numbers of cells, more prominent
      vascularity, and often increased collagen content. The hypercellular regions were
      not associated with cytologic atypia of the constituent cells, mitotic activity,
      or necrosis. Follow-up information was available for 32 patients and ranged from
      3 to 108 (average 30) months. No tumor recurred or metastasized. Areas of
      hypercellularity are common in IMs. Their recognition is important to avoid an
      erroneous diagnosis of sarcoma.

PMID- 9777985
TI  - Low-grade myofibroblastic sarcoma: analysis of 18 cases in the spectrum of
      myofibroblastic tumors.
AB  - The clinicopathologic, immunohistochemical, and ultrastructural features of a
      seemingly distinctive low-grade spindle cell sarcoma showing myofibroblastic
      differentiation have been analyzed in a series of 18 patients. The age range of
      the patients (7 women and 11 men) was 19-72 years (median: 42 years). A painless,
      enlarging mass was the most common clinical presentation. Five tumors arose in
      the oral cavity (including four lesions in the tongue), four in the lower
      extremities and three in the upper extremities, four cases in the
      abdominal/pelvic cavity, and two on the trunk. Eight soft-tissue cases involved
      skeletal muscle, three cases were located in perifascial tissues, and two arose
      in subcutaneous tissue. Tumor size ranged from 1.4 to 17 cm (median: 4 cm); in
      six cases (of which four were abdominal/pelvic) the lesion was larger than 5 cm.
      All patients were treated surgically, and four received additional adjunctive
      therapy. Histologically, most cases were cellular lesions showing a diffusely
      infiltrative pattern, and were composed of spindle-shaped tumor cells arranged
      mainly in fascicles. Tumor cells had poorly defined, palely eosinophilic
      cytoplasm and fusiform nuclei, which were either tapering and wavy or plumper and
      vesicular with indentations and small inconspicuous nucleoli. Tumor cells were
      set in a collagenous matrix often with prominent hyalinization. Mild nuclear
      atypia was noted in 16 cases; in the other 2 cases, and in the metastases of one
      other lesion, a greater degree of nuclear atypia was seen. In all but one case,
      the mitotic rate ranged from 1 to 6 mitoses in 10 HPFs (mean: 2/10 HPFs); in a
      single case, there were more than 20 mitoses in 10 HPFs. Immunohistochemically,
      all cases stained positively for at least one myogenic marker; 12 cases were
      positive for desmin, 11 for alpha-smooth muscle actin, and 6 for muscle actin
      (HHF35). Seven neoplasms were desmin positive/ alpha-smooth-muscle actin
      negative, and five cases were desmin negative/alpha-smooth-muscle actin positive
      emphasizing the variable immunophenotype of myofibroblastic lesions. In addition,
      7 of 10 tumors stained at least focally positive for fibronectin. Ultrastructural
      examination in five cases showed characteristic features of myofibroblasts.
      Follow-up in 11 patients (median: 29 months) revealed local recurrence in 2
      cases, and multiple distant soft-tissue, intraosseous, and pulmonary metastases
      in one other patient. Low-grade myofibroblastic sarcoma seems to represent a
      distinct entity in the spectrum of low-grade myofibroblastic neoplasms and is
      distinguishable from fibromatosis, myofibromatosis, solitary fibrous tumor,
      fibrosarcoma, and leiomyosarcoma.

PMID- 9777986
TI  - Pseudohyperplastic prostatic adenocarcinoma.

PMID- 9777987
TI  - K-ras oncogene mutations in osteoclast-like giant cell tumors of the pancreas and
      liver: genetic evidence to support origin from the duct epithelium.
AB  - Osteoclast-like giant cell tumors (OCGTs) of the pancreas and liver are enigmatic
      tumors. Despite their striking morphologic resemblance to certain mesenchymal
      tumors of bone and tendon sheath, it has been suggested that these tumors may, in
      fact, arise from epithelial precursors. It is also unclear whether the osteoclast
      like giant cells in OCGTs are neoplastic or nonneoplastic. We identified OCGTs of
      the pancreas and liver that were associated with atypical intraductal epithelial
      proliferations or mucinous cystic neoplasms. To determine the relationship
      between the noninvasive epithelial proliferations and the infiltrating OCGTs,
      each individual component was analyzed for mutations at codon 12 of the K-ras
      oncogene. Four of the five-duct epithelial lesions harbored activating mutations
      of the K-ras oncogene. In each case, the same K-ras mutation was also present in
      the mononuclear cells from the paired OCGT. Moreover, these same mutations were
      detected when the osteoclast-like giant cells were individually microdissected
      and analyzed. A panel of immunohistochemical stains was performed, and the
      osteoclast-like giant cells demonstrated macrophage differentiation. These cells
      were consistently reactive for the monocyte/macrophage marker KP1, but showed
      absent staining for a panel of epithelial markers. The infiltrating mononuclear
      cells lacked strong staining for epithelial markers and monocyte/macrophage
      markers. These findings suggest that OCGTs of the pancreas and liver are
      undifferentiated carcinomas that arise directly from intraductal epithelial
      precursors. The finding of K-ras mutations in the osteoclast-like giant cells may
      reflect their propensity to phagocytize tumor cells.

PMID- 9777989
TI  - Neural cell adhesion molecules (NCAM) and NCAM-PSA expression in neuroendocrine
      lung tumors.
AB  - Neural cell adhesion molecules (NCAM) represent specific markers of
      neuroendocrine (NE) differentiation in lung cancer. Because the polysialic acid
      form (NCAM-PSA) has reduced adhesion properties, we hypothesized that NCAM-PSA
      expression could favor metastatic spread. Immunostaining of NCAM and NCAM-PSA
      were therefore compared in 120 NE lung tumors, including 17 typical carcinoids, 3
      atypical carcinoids, 30 large cell NE carcinomas and 70 small cell lung
      carcinomas, as compared with 25 adenocarcinomas and 25 squamous cell carcinomas.
      Neural cell adhesion molecules were negative in adenocarcinomas and squamous cell
      carcinomas but were constantly expressed in all NE tumors from typical carcinoids
      to small cell lung carcinomas. NCAM-PSA expression was significantly more
      frequent in high-grade tumors, with 24 of 30 positive cases in large cell NE
      carcinomas and 65 of 70 positive cases in small cell lung carcinoma, than in
      carcinoids with 10 of 17 and 2 of 3 positive cases in typical carcinoids and
      atypical carcinoids, respectively. The neural cell adhesion molecule-polysialic
      acid form scores of staining were significantly higher in high-grade as compared
      with low-grade tumors (p = 0.002), and were correlated with nodal spread (p =
      0.04) and metastasis (p = 0.016) across histologic classes but not in individual
      tumor type. We conclude that NCAM-PSA connotes poor differentiation and
      aggressive clinical behavior in the spectrum of NE lung tumors, but cannot be
      regarded as a prognostic factor in individual tumor classes.

PMID- 9777988
TI  - Splenic pathology in myelodysplasia: a report of 13 cases with clinical
      correlation.
AB  - Splenomegaly is uncommon in myelodysplasia (MDS) and, although cytopenias may be
      severe, therapeutic splenectomy is rarely performed. We report the histologic,
      histochemical, and immunophenotypic findings of nine cases of surgical
      splenectomy and four postmortem spleens from MDS patients. Four histologic
      patterns were identified: one dominated by erythrophagocytosis, one characterized
      by red pulp plasmacytosis, one with extramedullary hematopoiesis as the only
      salient finding, and one with marked red pulp expansion caused by a monocytic
      proliferation. Wright-Giemsa and histochemical stains were performed on touch
      preparations in three cases and played a critical role in the precise
      subclassification of one MDS patient's hematologic disorder, which ultimately
      proved to be chronic myelomonocytic leukemia. Splenectomy led to sustained
      improvement of cytopenias in three cases, but did not eliminate transfusion
      dependence for the remaining patients. Three splenectomy cases exhibited
      clustered Leder-negative mononuclear elements: two of these patients experienced
      disease progression to refractory anemia with excess blasts in transformation or
      acute myelogenous leukemia during post-splenectomy follow-up, whereas none of the
      three splenectomy patients without clustered mononuclear elements did. We
      conclude that splenomegaly in MDS usually reflects the sequelae of dyspoiesis
      rather than evidence of a proliferative phase, that clustering of Leder-negative
      large cells may correlate with either a substantial monocytic component or,
      possibly, increased risk of disease progression, and that the spleen can provide
      diagnostic as well as prognostic information in MDS patients with splenomegaly.

PMID- 9777990
TI  - Massive localized lymphedema in the morbidly obese: a histologically distinct
      reactive lesion simulating liposarcoma.
AB  - We report 14 cases of a soft tissue lesion in the limbs of morbidly obese adults
      that presents as a large mass and histologically simulates well-differentiated
      liposarcoma (WDL). Based on its distinctive clinical setting and morphologic
      identity to diffuse lymphedema we have termed this process massive localized
      lymphedema (MLL). All cases occurred in morbidly obese adults (mean weight 372
      lbs; mean age 47 years). Women predominated (9 women; 5 men). The lesions
      affected the proximal medial aspect of the extremities (12 thigh; 2 arm) and were
      unilateral in all but two patients. Etiologically significant antecedent events
      include ipsilateral axillary lymphadenectomy in both patients with arm lesions,
      chronic lymphedema resulting from vein-stripping 10 years prior in one patient.
      inguinal lymphadenectomy for anal carcinoma in another patient, and significant
      blunt trauma to the inner thigh during a motor vehicle accident in a third
      patient. The tumors were long standing ( I-IO years) and extremely large (mean
      size 33.4 cm, 7408 g). Clinically, they were diffuse, ill-defined masses that
      histologically consisted of lobules of mature fat interrupted by expanded
      connective tissue septa. The constituents of the septa were fine, fibrillary
      collagen, edema fluid, and uniformly distributed fibroblasts. Clusters of
      capillaries were frequently found at the interface between fat and connective
      tissue. The widened septa simulated the fibrous bands of sclerosing WDL, but MLL
      lacks the degree of nuclear atypia seen in the former. The consistent clustering
      of reactive vessels at the interface between the fat and fibrous tissue also
      contrasted with WDL. Six patients experienced persistent or recurrent lesions
      within 10 months to 10 years. No aggressive growth or histologic progression was
      observed during this time, however. Awareness of the features of MLL is important
      to avoid misclassification of this reactive lesion with WDL.

PMID- 9777991
TI  - Malignant phyllodes tumor of breast with lung metastases mimicking the primary.
AB  - We report a case of recurrent malignant phyllodes tumor with liposarcomatous
      transformation metastasizing to the lung. The unusual feature of this case was
      that the metastases reproduced the primary tumor and contained ductal structures
      and elements of sarcoma. The origin of the ductal structures in the lung
      metastases was confirmed to be from the phyllodes tumor, on the basis of their
      immunophenotype. The epithelial cells were positive for steroid receptors and
      GCDFP-15, and the myoepithelial cells were positive for anti-smooth-muscle
      specific proteins. We also reevaluated by immunohistochemistry a case of
      phyllodes tumor previously published by West et al., allegedly containing
      epithelial structures of supposed breast origin within lung metastases. The
      epithelial component was shown to consist of entrapped alveolar lining cells.

PMID- 9777992
TI  - Disseminated mucosal papilloma/condyloma secondary to human papillomavirus.
AB  - This report details the histopathologic findings in a woman who acquired the
      human papillomavirus 6/11 in her late teens and developed papilloma/condyloma of
      the nasopharynx, oropharynx, anogenital region, urethra, and urinary bladder.
      General evaluations of immune function reveal no defect, and there was no
      evidence of HIV infection. The morphologic expression of HPV 6/11 infection
      appears to be completely dependent on the mucosal epithelium affected. The
      complete spectrum of benign and premalignant epithelial changes induced by the
      human papillomavirus family-papilloma, verrucae, condyloma acuminatum, epithelial
      hyperplasia, and dysplasia-were present in this patient with a single
      papillomavirus infection. We postulate that this patient has a specific immune
      deficiency that limits her ability to control local infection and spread of the
      papillomavirus.

PMID- 9777993
TI  - A new type of peritoneal encapsulation of the small bowel.

PMID- 9777994
TI  - Nuclear grooves in papillary (chromophil) renal cell carcinoma.

PMID- 9777995
TI  - EEGs, EEG processing, and the bispectral index.

PMID- 9777996
TI  - The Internet: where do we want to go tomorrow?

PMID- 9777997
TI  - Gary Strichartz: life among local anesthetics. Recipient of 1998 Excellence in
      Research Award.

PMID- 9777998
TI  - Intravenous almitrine bismesylate reversibly induces lactic acidosis and hepatic
      dysfunction in patients with acute lung injury.
AB  - BACKGROUND: Intravenous almitrine, which augments hypoxic pulmonary
      vasoconstriction, is used for short-term improvement of arterial oxygenation.
      However, recent research has suggested a potentially harmful effect on lactate
      metabolism and hepatic function. METHODS: Arterial oxygenation, hemodynamic
      parameters, plasma lactate, and hepatic function were monitored prospectively in
      25 patients with acute lung injury (defined as a ratio of arterial oxygen
      pressure to inspiratory oxygen fraction < or = 150 mmHg) who where treated with
      intravenous almitrine. In 21 of 25 patients, acute lung injury was related to
      primary lung lesions, including pneumonia, postcardiosurgical atelectasis, and
      lung contusions. RESULTS: Intravenous almitrine increased the ratio of arterial
      oxygen pressure to inspiratory oxygen fraction from 93 +/- 33 mmHg to 207 +/- 107
      mmHg (mean +/- SD). In eight patients (three men), the plasma lactate
      concentration increased by an average of +3.5 +/- 1.8 mM, and the pH and
      bicarbonate concentration both decreased during the first 24 h of treatment. In
      this group of patients, the total bilirubin concentration was elevated before
      almitrine administration, and the results of other hepatic function tests, such
      as aspartate aminotransferase, alanine aminotransferase, and prothrombin time,
      were altered by almitrine administration. Therefore, intravenous almitrine was
      discontinued. Lactic acidosis and hepatic dysfunction improved. In the other 17
      patients (14 men), the plasma lactate concentration and the hepatic function
      tests remained unaltered during intravenous almitrine therapy for > 60 h.
      Univariate and multivariate analyses revealed that an abnormal plasma
      concentration of total bilirubin before almitrine administration and female
      gender were the two factors significantly linked with lactic acidosis during
      almitrine infusion. CONCLUSIONS: This study confirms that intravenous almitrine
      greatly improves arterial oxygenation in patients with acute lung injury but may
      also induce lactic acidosis and hepatic dysfunction. The coexistence of lactic
      acidosis and hepatic dysfunction in the same patients strongly suggests that the
      liver is the primary source of intravenous almitrine-induced lactic acidosis.

PMID- 9777999
TI  - Effects of respiratory alkalosis and acidosis on myocardial blood flow and
      metabolism in patients with coronary artery disease.
AB  - BACKGROUND: Variation of the arterial carbon dioxide partial pressure (PaCO2) is
      not uncommon in anesthetic practice. However, little is known about the
      myocardial consequences of respiratory alkalosis and acidosis, particularly in
      patients with coronary artery disease. The aim of the current study was to
      investigate the effects of variation in PaCO2 on myocardial blood flow (MBF),
      metabolism, and systemic hemodynamics in patients before elective coronary artery
      bypass graft surgery. METHODS: In 10 male anesthetized patients, measurements of
      MBF, myocardial contractility, metabolism, and systemic hemodynamics were made in
      a randomized sequence at PaCO2 levels of 30, 40, and 50 mmHg, respectively. The
      MBF was measured using the Kety-Schmidt technique with argon as a tracer. End
      diastolic left ventricular pressure and the maximal increase of left ventricular
      pressure were assessed using a manometer-tipped catheter. RESULTS: The cardiac
      index significantly changed with varying PaCO2 levels (hypocapnia, - 9%;
      hypercapnia, 13%). This reaction was associated with inverse changes in systemic
      vascular resistance index levels. The MBF significantly increased by 15% during
      hypercapnia, whereas no change was found during hypocapnia. Myocardial oxygen and
      glucose uptake and the maximal increase of left ventricular pressure were not
      affected by varying PaCO2 levels. CONCLUSIONS: In anesthetized patients with
      coronary artery disease, short-term variations in PaCO2 have significant effects
      on MBF but do not influence global myocardial oxygen and glucose uptake. Changes
      in systemic hemodynamics associated with respiratory alkalosis and acidosis are
      caused by changes in systemic vascular resistance rather than by alterations in
      myocardial contractility.

PMID- 9778000
TI  - Antiemetic activity of propofol after sevoflurane and desflurane anesthesia for
      outpatient laparoscopic cholecystectomy.
AB  - BACKGROUND: Controversy exists regarding the effectiveness of propofol to prevent
      postoperative nausea and vomiting. This prospective, randomized, single-blinded
      study was designed to evaluate the antiemetic effectiveness of 0.5 mg/kg propofol
      when administered intravenously after sevoflurane- compared with desflurane-based
      anesthesia. METHODS: Two hundred fifty female outpatients undergoing laparoscopic
      cholecystectomy were assigned randomly to one of four treatment groups. All
      patients were induced with intravenous doses of 2 mg midazolam, 2 microg/kg
      fentanyl, and 2 mg/kg propofol and maintained with either 1-4% sevoflurane
      (groups 1 and 2) or 2-8% desflurane (groups 3 and 4) in combination with 65%
      nitrous oxide in oxygen. At skin closure, patients in groups 1 and 3 were
      administered 5 ml intravenous saline, and patients in groups 2 and 4 were
      administered 0.5 mg/kg propofol intravenously. Recovery times were recorded from
      discontinuation of anesthesia to awakening, orientation, and readiness to be
      released home. Postoperative nausea and vomiting and requests for antiemetic
      rescue medication were evaluated during the first 24 h after surgery. RESULTS:
      Propofol, in an intravenous dose of 0.5 mg/kg, administered at the end of a
      sevoflurane-nitrous oxide or desflurane-nitrous oxide anesthetic prolonged the
      times to awakening and orientation by 40-80% and 25-30%, respectively. In group 2
      (compared with groups 1, 3, and 4), the incidences of emesis (22% compared with
      47%, 53%, and 47%) and requests for antiemetic rescue medication (19% compared
      with 42%, 50%, and 47%) within the first 6 h after surgery were significantly
      lower, and the time to home-readiness was significantly shorter in duration (216
      +/- 50 min vs. 249 +/- 49 min, 260 +/- 88 min, and 254 +/- 72 min, respectively).
      CONCLUSIONS: A subhypnotic intravenous dose of propofol (0.5 mg/kg) administered
      at the end of outpatient laparoscopic cholecystectomy procedures was more
      effective in preventing postoperative nausea and vomiting after a sevoflurane
      based (compared with a desflurane-based) anesthetic.

PMID- 9778001
TI  - Effect of isoflurane on the auditory steady-state response and on consciousness
      in human volunteers.
AB  - BACKGROUND: The auditory steady state response (ASSR) is a sustained electrical
      response of the brain to auditory stimuli delivered at fast rates (30-50
      responses/s). The aim of this study was to evaluate the effect of 0.26-0.50%
      isoflurane on the ASSR and on consciousness, defined as responsiveness to verbal
      commands. METHODS: Ten volunteers (21-31 yr) participated. Isoflurane was
      administered at three stable, end-tidal concentrations: 0.26%, 0.38%, and 0.50%.
      The ASSR in response to 18,000 stimuli (500-Hz tonebursts, 10 ms, 82-dB, the
      right ear, 35-45 bursts/s) was recorded from the vertex with reference to the
      right mastoid. Recordings were made during baseline, at each isoflurane
      concentration, and during recovery. RESULTS: The mean (SD) ASSR amplitudes were
      0.32 (0.23) microV during baseline, 0.24 (0.17) microV during 0.26% isoflurane,
      0.09 (0.05) microV during 0.38% isoflurane, 0.04 (0.03) microV during 0.50%
      isoflurane, and 0.29 (0.33) microV during recovery. The amplitude during baseline
      and recovery was larger than during 0.38% and 0.50% isoflurane (P < 0.001). The
      amplitude at 0.26% was larger than at the other concentrations (P < 0.025). The
      logarithm of the ASSR amplitude was related linearly to the concentration of
      isoflurane (r = 0.85; P < 0.0001). The prediction probability (Pk) for loss of
      consciousness was 0.95 for both ASSR and measured isoflurane concentration. An
      ASSR amplitude < 0.07 microV was always associated with unconsciousness.
      CONCLUSIONS: The ASSR is attenuated in a concentration-dependent manner by
      isoflurane. Suppression of consciousness and maximal attenuation of ASSR occur in
      the same isoflurane concentration range. Profound attenuation of ASSR appears to
      reflect unconsciousness, defined as unresponsiveness to verbal commands.

PMID- 9778002
TI  - Concentration-response relationships for fentanyl and sufentanil in patients
      undergoing coronary artery bypass grafting.
AB  - BACKGROUND: Concentration-response relationships for sufentanil and fentanyl are
      undefined in patients undergoing coronary artery bypass grafting. METHODS:
      Separate studies of sufentanil and fentanyl were performed in lorazepam
      premedicated patients undergoing coronary artery bypass grafting. Patients were
      assigned randomly to groups with different prebypass effect-site opioid
      concentrations targeted by computer-assisted infusion. The target sufentanil
      concentrations were 0.4 ng/ml (group LS, n = 11), 0.8 ng/ml (group MS, n = 10),
      and 1.2 ng/ml (group HS, n = 11); the target fentanyl concentrations were 5 ng/ml
      (group LF, n = 7), 10 ng/ml (group MF, n = 7), and 15 ng/ml (group HF, n = 6).
      Propofol at a dose of 1 mg/kg was administered at induction of anesthesia and
      isoflurane was used for hemodynamic control Hemodynamics, end-tidal isoflurane
      concentration, and opioid concentration in arterial blood were measured at
      specific intervals. RESULTS: Intraoperative opioid concentrations were constant,
      averaging 0.71 +/- 0.13, 1.25 +/- 0.21, and 2.03 +/- 0.46 ng/ml for groups LS,
      MS, and HS, respectively, and 7.3 +/- 1.1, 13.2 +/- 2.2, and 24.4 +/- 5.8 ng/ml
      for groups LF, MF, and HF, respectively (all mean +/- SD). Isoflurane
      requirements were significantly greater in group LS than in groups MS and HS and
      greater in group LF than in groups MF and HF. The serum opioid and end-tidal
      isoflurane concentrations were correlated significantly. There were no intergroup
      differences in hemodynamics. CONCLUSIONS: Serum sufentanil and fentanyl
      concentrations of 0.71 +/- 0.13 ng/ml and 7.3 +/- 1.3 ng/ml, respectively, are on
      the steep parts of the concentration-response relationships and facilitate
      prebypass hemodynamic control in patients undergoing coronary artery bypass
      grafting with opioid-isoflurane anesthesia. Concentrations of sufentanil > or =
      1.25 +/- 0.21 ng/ml and of fentanyl > or = 13.3 +/- 2.2 ng/ml minimize isoflurane
      requirements but do not improve hemodynamic control.

PMID- 9778003
TI  - Combined intravenous lidocaine and inhaled salbutamol protect against bronchial
      hyperreactivity more effectively than lidocaine or salbutamol alone.
AB  - BACKGROUND: Airway instrumentation in persons with asthma is linked to the risk
      of life-threatening bronchospasm. To attenuate the response to airway irritation,
      intravenous lidocaine is recommended (based on animal experiments) and mitigates
      the response to histamine inhalation in asthmatic volunteers. However, the
      effects of lidocaine have not been compared with standard prophylaxis with beta
      sympathomimetic aerosols. Therefore, the effect of lidocaine, salbutamol,
      combined treatment, and placebo control were tested in awake volunteers with
      bronchial hyperreactivity. METHODS: After approval from the local ethics
      committee, 15 persons, who were selected because they showed a decrease in forced
      expiratory volume in 1 s (FEV1) more than 20% of baseline in response to inhaled
      histamine in a concentration less than 18 mg/ml (PC20), were enrolled in a
      placebo-controlled, double-blind, and randomized study. The challenge was
      repeated on four different days and the volunteers were pretreated with either
      intravenous lidocaine, inhalation of salbutamol, inhalation of salbutamol plus
      intravenous lidocaine, or placebo. Lidocaine plasma concentrations were also
      measured. Statistical analyses included the Friedman test and Wilcoxon's rank
      sum. RESULTS: The baseline PC20 was 6.4 +/- 4.3 mg/ml. Intravenous lidocaine and
      salbutamol aerosol both significantly increased the histamine threshold to 14.2
      +/- 9.5 mg/ml and 16.8 +/- 10.9 mg/ml, respectively (mean +/- SD). However, the
      combination of lidocaine and salbutamol significantly increased the PC20 even
      further to 30.7 +/- 15.7 mg/ml than did salbutamol or lidocaine alone.
      CONCLUSIONS: In volunteers with bronchial hyperreactivity, both lidocaine and
      salbutamol attenuate the response to an inhalational histamine challenge, and
      their combined administration has much greater effects than does either drug
      alone. Accordingly, pretreatment of patients with bronchial hyperreactivity with
      both beta-mimetic aerosol and intravenous lidocaine is recommended before airway
      irritation.

PMID- 9778004
TI  - Population pharmacodynamics and pharmacokinetics of remifentanil as a supplement
      to nitrous oxide anesthesia for elective abdominal surgery.
AB  - BACKGROUND: Remifentanil blood concentrations necessary for adequate
      intraoperative anesthesia have not been defined. The goal of this study was to
      determine the blood concentrations of remifentanil needed for anesthesia with 66%
      nitrous oxide during intraabdominal surgery. In addition, the pharmacokinetics of
      remifentanil and the effects of covariates on both the pharmacodynamics and the
      pharmacokinetics were determined. METHODS: Anesthesia was induced and maintained
      with 66% nitrous oxide in oxygen and remifentanil. Remifentanil was administered
      by a computer-controlled infusion pump that rapidly attained, and then
      maintained, constant remifentanil blood concentrations. If the patient showed
      signs of inadequate anesthesia (autonomic or somatic response), the target
      concentration was increased by 1 or 2 ng/ml. If no response occurred during a 15
      min period, the concentration was decreased by 1 or 2 ng/ml. Remifentanil
      pharmacodynamics and pharmacokinetics were estimated using NONMEM. RESULTS: The
      remifentanil blood concentration for which there is a 50% probability of adequate
      anesthesia during abdominal surgery (Cb50) with 66% nitrous oxide was 4.1 ng/ml
      in men and 7.5 ng/ml in women. The Cb50 values for prostatectomy, nephrectomy,
      and other abdominal procedures were 3.8, 5.6, and 7.5 ng/ml, respectively.
      Remifentanil pharmacokinetics were best described by a two-compartment model with
      lean body mass as a significant covariate, where V1 = 0.129(lean body mass-50) +
      3.79 l, V2 = 6.87 l, CL1 = 0.0389(lean body mass-50) + 2.34 l/min and CL2 = 1.14
      l/min. CONCLUSIONS: The Cb50 differed according to patient gender. However,
      because surgery type was not specified for each man or woman, this may reflect a
      difference in surgical procedure.

PMID- 9778005
TI  - Non-thermoregulatory shivering in patients recovering from isoflurane or
      desflurane anesthesia.
AB  - BACKGROUND: Although cold-induced shivering is an obvious source of
      postanesthetic tremor, other causes may contribute. Consistent with this theory,
      the authors had previously identified an abnormal clonic component of
      postoperative shivering and proposed that it might be nonthermoregulatory. A
      subsequent study, however, failed to identify spontaneous muscular activity in
      normothermic volunteers. These data suggested that the initial theory was
      erroneous or that a yet-to-be identified factor associated with surgery might
      facilitate shivering in patients after operation. Therefore, the authors tested
      the hypothesis that some postoperative tremor is nonthermoregulatory. METHODS:
      One hundred twenty patients undergoing major orthopedic operation were observed.
      They were grouped randomly to receive maintenance anesthesia with nitrous oxide
      and isoflurane (0.8 +/- 0.4%) or desflurane (3.4 +/- 1.1%). Twenty patients in
      each group were allowed to become hypothermic, whereas normal body temperatures
      were maintained in the others (tympanic membrane temperature exceeding
      preinduction values). Arteriovenous shunt vasoconstriction was evaluated using
      forearm-minus-fingertip skin-temperature gradients; gradients less than 0 degrees
      C identified vasodilation. Postanesthetic shivering was graded by a blinded
      investigator. Tremor in patients who were normothermic and vasodilated was
      considered nonthermoregulatory. RESULTS: Thermoregulatory responses were similar
      after isoflurane or desflurane anesthesia. Approximately 50% of the unwarmed
      patients shivered. Shivering was observed in 27% of the patients who were
      normothermic; 55% of this spontaneous muscular activity occurred in vasodilated
      patients. Among the normothermic patients, 15% fulfilled the authors' criteria
      for nonthermoregulatory tremor. CONCLUSIONS: The incidence of postoperative
      shivering is inversely related to core temperature. Therefore, it was not
      surprising that shivering was most common among the hypothermic patients. The
      major findings, however, were that shivering remained common even among patients
      who were kept scrupulously normothermic and that many shivered while they were
      vasodilated. Thus, postoperative patients differ from nonsurgical volunteers in
      demonstrating a substantial incidence of nonthermoregulatory tremor.

PMID- 9778006
TI  - Cerebrovascular CO2 reactivity during anesthesia in patients with diabetes
      mellitus and peripheral vascular disease.
AB  - BACKGROUND: Diabetes mellitus (DM) and systemic atherosclerosis are risk factors
      for stroke. Although the origins of increased risk are complex, one possibility
      is that cerebrovascular reactivity is impaired and does not allow the brain to
      compensate for aberrations in physiology. The current study tested this issue by
      evaluating mean blood flow velocity of the middle cerebral artery (Vmca) and
      carbon dioxide reactivity during anesthesia in patients with DM and peripheral
      vascular disease (PVD). METHODS: Fifty-two patients were observed: 20 patients
      with DM (the DM group), 12 patients with PVD (the PVD group), and 20 patients
      classified as American Society of Anesthesiologists physical status 1 or 2 (the
      control group). The Vmca was measured using transcranial Doppler ultrasonography
      during isoflurane-nitrous oxide anesthesia. After measuring baseline Vmca at a
      partial pressure of carbon dioxide in arterial blood (PaCO2) of 37.7 +/- 4.5 mmHg
      (mean +/- SD), measurements were repeated at a PaCO of 44.2 +/- 3.8 mmHg, and the
      carbon dioxide reactivity (absolute value: cm x s(-1) x mmHg(-1); relative value:
      percentage of baseline Vmca/mmHg) was calculated. RESULTS: The baseline Vmca of
      the DM group (51 +/- 12 cm/s) was significantly greater than those of the control
      group (42 +/- 6 cm/s) and the PVD group (42 +/- 13 cm/s). The absolute and
      relative values of carbon dioxide reactivity in the DM group (3.1 +/- 1.3 cm x s(
      1) x mmHg(-1); 6.3 +/- 2.4%/mmHg) were significantly greater than or equivalent
      to those of the control group (2.3 +/- 0.8 cm x s(-1) x mmHg(-1); 5.3 +/-
      1.7%/mmHg), respectively. In the PVD group, the baseline Vmca was equivalent to
      the control group, but the carbon dioxide reactivity (1.1 +/- 0.5 cm x s(-1) x
      mmHg(-1) 2.8 +/- 1.2%/mmHg) was significantly less. CONCLUSIONS: The patients
      with DM have increased baseline cerebral blood flow velocity and normal carbon
      dioxide reactivity during anesthesia. The patients with PVD have decreased carbon
      dioxide reactivity, but baseline flow velocity is maintained.

PMID- 9778007
TI  - The pharmacodynamic interaction between propofol and fentanyl with respect to the
      suppression of somatic or hemodynamic responses to skin incision, peritoneum
      incision, and abdominal wall retraction.
AB  - BACKGROUND: Sufficient propofol or fentanyl doses necessary to prevent the
      response to skin incision do not necessarily attenuate hemodynamic responses
      during surgery. The goal of this study was to characterize the pharmacodynamic
      interaction between propofol and fentanyl with respect to the suppression of
      somatic or hemodynamic responses after three stimuli: skin incision, peritoneum
      incision, and abdominal wall retraction. METHODS: Propofol and fentanyl were
      administered via computer-assisted continuous infusion to provide equilibration
      between plasma-blood and biophase concentrations. Patients were randomized to
      nine groups that received predetermined concentrations of fentanyl (from 0 to 9
      ng/ml). Each patient was administered different target concentrations of
      propofol. Somatic and hemodynamic responses were measured before and after each
      of three different stimulations: skin incision (si), peritoneum incision (pi),
      and abdominal wall retraction (ret). The propofol plasma concentrations at which
      50% of the patients did not respond to each type of stimulation (Cp50si, Cp50pi,
      and Cp50ret) were calculated by fitting the Loewe synergistic model. RESULTS: For
      propofol alone, Cp50si, Cp50pi, and Cp50ret were 12.9, 17.1, and 19.4 microg/ml,
      respectively. Increasing the fentanyl concentration markedly reduced propofol
      Cp50si, Cp50pi, and Cp50ret for somatic response, indicating the potential
      synergistic interaction of both drugs. During the prestimulation period, fentanyl
      did not decrease systolic blood pressure; however, propofol specifically
      decreased systolic blood pressure. Both drugs had a synergistic drug interaction
      on the systolic blood pressure increase after various surgical stimulations.
      Fentanyl and propofol concentrations that suppressed both the 50% probability of
      somatic response and the 50% probability of moderate hemodynamic change defined
      by the 15% systolic blood pressure increase over the prestimulation value were
      3.6 ng/ml and 2.5 microg/ml for skin incision, 8.4 ng/ml and 1.6 microg/ml for
      peritoneum incision, and 5.9 ng/ml and 5.1 microg/ml for wall retraction,
      respectively. CONCLUSIONS: The anesthesia requirements for stimuli that are more
      intense than skin incision should be considered during abdominal surgery. Somatic
      and hemodynamic responses varied depending on the type of surgical stimuli.

PMID- 9778008
TI  - Prospective, randomized comparison of deep or superficial cervical plexus block
      for carotid endarterectomy surgery.
AB  - BACKGROUND: Carotid endarterectomy may be performed under cervical plexus block
      with local anesthetic supplementation by the surgeon as necessary during surgery.
      It is unclear, however, whether deep or superficial cervical plexus block offers
      the best operating conditions or patient satisfaction. Therefore, the authors
      compared the two in patients undergoing carotid endarterectomy. METHODS: Forty
      patients undergoing carotid endarterectomy were randomized to receive either a
      superficial or a deep cervical plexus block with 20 ml bupivacaine, 0.375%.
      Outcomes subjected to statistical analysis included supplemental anesthetic
      supplementation with lidocaine, 1%, by the surgeon, dermatomes affected by the
      block, paresthesia during block placement, postoperative pain scores, and
      analgesic requirements. RESULTS: Median supplemental lidocaine requirements were
      6 ml (range, 0.5 to 20 ml) in the deep block group and 6 ml (range, 0 to 20 ml)
      in the superficial block group (P = 0.7323). Patients in the deep block group who
      reported paresthesia during block placement required less lidocaine
      supplementation (median, 2; range, 0.5 to 20 ml) than the 9.5 ml (range, 6 to
      15.5 ml) required by those who did not experience paresthesia (P = 0.0113).
      Compared with patients in the superficial block group, those in the deep block
      group were less likely to need analgesia in the first 24 h after operation (P =
      0.047), and those who required analgesia received it later (6.6 +/- 4.1 vs. 3.9
      +/- 1.4 h after operation; Student's t test, P = 0.02). One patient in each group
      expressed dissatisfaction with the technique. CONCLUSIONS: Carotid endarterectomy
      may be performed satisfactorily during superficial or deep cervical plexus block
      placement with no differences in terms of supplemental local anesthetic
      requirements, although this is influenced by whether paresthesia is elicited
      during placement of the deep block. Therefore, the clinician's decision to use
      one block rather than another need not be based on any assumed superiority of one
      block based on intraoperative conditions or patient satisfaction.

PMID- 9778009
TI  - A multi-center study of intrathecal neostigmine for analgesia following vaginal
      hysterectomy.
AB  - BACKGROUND: Intrathecal neostigmine injection produces analgesia in volunteers
      and reduces hypotension from intrathecal bupivacaine in animals. Initial clinical
      trials with neostigmine studied doses of more than 100 microg, but animal studies
      suggest that smaller doses may be effective. In addition, all controlled clinical
      trials of neostigmine have come from one Brazilian university. This multicenter,
      placebo-controlled trial investigated the effects of 25-75 microg intrathecal
      neostigmine on analgesia and blood pressure in women undergoing vaginal
      hysterectomy. METHODS: After institutional review board approval was obtained at
      the three university centers, and after patients gave informed consent, 92 women
      scheduled for vaginal hysterectomy were randomized to receive an intrathecal
      injection of 2 ml bupivacaine, 0.75%, in dextrose plus either 1 ml saline or 25,
      50, or 75 microg neostigmine. Blood pressure, heart rate, pain and nausea (both
      assessed by visual analog scale), and intravenous morphine use were recorded
      during surgery and at specified intervals afterward. RESULTS: Morphine use was
      reduced similarly by all doses of neostigmine. Only the 75-microg dose of
      neostigmine increased the nausea score in the recovery room. The incidence of
      treatment for nausea was greater in patients receiving neostigmine (61%) than in
      those receiving saline placebo (29%) and was unaffected by neostigmine dose.
      Neostigmine did not reduce the incidence of hypotension from bupivacaine.
      CONCLUSION: These data in patients after vaginal hysterectomy suggest that
      analgesia from intrathecal neostigmine may occur at doses less than 50 microg. In
      these doses, neostigmine does not reduce spinal bupivacaine-induced hypotension
      but may increase the need for treatment of nausea.

PMID- 9778011
TI  - Mechanistic aspects of carbon monoxide formation from volatile anesthetics.
AB  - BACKGROUND: Desflurane, enflurane and isoflurane can be degraded to carbon
      monoxide (CO) by carbon dioxide absorbents, whereas sevoflurane and halothane
      form negligible amounts of CO. Carbon monoxide formation is greater with drier
      absorbent, and with barium hydroxide, than with soda lime. The mechanism, role of
      absorbent composition and water, and anesthetic structures determining CO
      formation are unknown. This investigation examined sequential steps in anesthetic
      degradation to CO. METHODS: Carbon monoxide formation from anesthetics and
      desiccated barium hydroxide lime or soda lime was determined at equimole and
      equiMAC concentrations. Carbon monoxide formation from deuterium-substituted
      anesthetics was also quantified. Proton abstraction from anesthetics by strong
      base was determined by deuterium isotope exchange. A reactive chemical
      intermediate was trapped and identified by gas chromatography-mass spectrometry.
      The source of the oxygen in CO was identified by 18O incorporation. RESULTS:
      Desflurane,enflurane,andisoflurane(difluoromethylethyl ethers), but not
      sevoflurane (monofluoromethyl ether), methoxyflurane (methy-ethyl ether), or
      halothane (alkane) were degraded to CO. The amount of CO formed was desflurane >
      or = enflurane > isoflurane at equiMAC and enflurane > desflurane > isoflurane at
      equimole concentrations. Proton abstraction from the difluoromethoxy carbon was
      greater with potassium than with sodium hydroxide, but unmeasurable with barium
      hydroxide. Carbon monoxide formation was correlated (r = 0.95-1.00) with
      difluoromethoxy (enflurane > desflurane > isoflurane > or = methoxyflurane =
      sevoflurane = 0) but not ethyl carbon proton abstraction. Deuterium substitution
      on enflurane and desflurane diminished CO formation. Chemical trapping showed
      formation of a difluorocarbene intermediate from enflurane and desflurane.
      Incorporation of H2(18)O in barium hydroxide lime resulted in C18O formation from
      unlabeled enflurane and desflurane. CONCLUSIONS: A difluoromethoxy group is a
      structural requirement for haloether degradation to CO. Results are consistent
      with initial base-catalyzed difluoromethoxy proton abstraction (potassium >
      sodium hydroxide, thus greater CO formation with barium hydroxide lime vs. soda
      lime) forming a carbanion (reprotonated by water to regenerate the anesthetic,
      hence requirements for relatively dry absorbent), carbanion decomposition to a
      difluorocarbene, and subsequent difluorocarbene reaction to form CO.

PMID- 9778010
TI  - Effects of intravenous general anesthetics on [3H]GABA release from rat cortical
      synaptosomes.
AB  - BACKGROUND: Potentiation by general anesthetics of gamma-aminobutyric acid (GABA)
      mediated inhibitory transmission in the central nervous system is attributed to
      GABA(A) receptor-mediated postsynaptic effects. However, the role of presynaptic
      mechanisms in general anesthetic action is not well characterized, and evidence
      for anesthetic effects on GABA release is controversial. The effects of several
      intravenous general anesthetics on [3H]GABA release from rat cerebrocortical
      synaptosomes (isolated nerve terminals) were investigated. METHODS: Purified
      synaptosomes were preloaded with [3H]GABA and superfused with buffer containing
      aminooxyacetic acid and nipecotic acid to inhibit GABA metabolism and reuptake,
      respectively. Spontaneous and elevated potassium chloride depolarization-evoked
      [3H]GABA release were evaluated in the superfusate in the absence or presence of
      various anesthetics, extracellular Ca2+, GABA receptor agonists and antagonists,
      and 2,4-diaminobutyric acid. RESULTS: Propofol, etomidate, pentobarbital, and
      alphaxalone, but not ketamine, potentiated potassium chloride-evoked [3H]GABA
      release (by 1.3 to 2.9 times) in a concentration-dependent manner, with median
      effective concentration values of 5.4 +/- 2.8 microM (mean +/- SEM), 10.1 +/- 2.1
      microM, 18.8 +/- 5.8 microM, and 4.4 +/- 2.0 microM. Propofol also increased
      spontaneous [3H]GABA release by 1.7 times (median effective concentration = 7.1
      +/- 3.4 microM). Propofol facilitation of [3H]GABA release was Ca2+ dependent and
      inhibited by bicuculline and picrotoxin, but was insensitive to pretreatment with
      2,4-diaminobutyric acid, which depletes cytoplasmic GABA pools. CONCLUSIONS: Low
      concentrations of propofol, etomidate, pentobarbital, and alphaxalone facilitated
      [3H]GABA release from cortical nerve terminals. General anesthetics may
      facilitate inhibitory GABA-ergic synaptic transmission by a presynaptic mechanism
      in addition to their well-known postsynaptic actions.

PMID- 9778012
TI  - Renal nerves are not involved in sodium and water retention during mechanical
      ventilation in awake dogs.
AB  - BACKGROUND: The role of renal nerves during positive end-expiratory pressure
      ventilation (PEEP) has only been investigated in surgically stressed,
      anesthetized, unilaterally denervated dogs. Anesthesia, sedation, and surgical
      stress, however, decrease urine volume and sodium excretion and increase renal
      sympathetic nerve activity independent of PEEP. This study investigated in awake
      dogs the participation of renal nerves in mediating volume and water retention
      during PEEP. METHODS: Eight tracheotomized, trained, awake dogs were used. The
      protocol consisted of 60 min of spontaneous breathing at a continuous positive
      airway pressure of 4 cm H2O, followed by 120 min of controlled mechanical
      ventilation with a mean PEEP of 15-17 cm H2O (PEEP), and 60 min of continuous
      positive airway pressure. Two protocols were performed on intact dogs, in which
      volume expansion had (hypervolemic; electrolyte solution, 0.5 ml x kg(-1) x min(
      1)) and had not (normovolemic) been instituted. This was repeated on the same
      dogs 2 or 3 weeks after bilateral renal denervation. RESULTS: Hypervolemic dogs
      excreted more sodium and water than did normovolemic dogs. There was no
      difference between intact and renal-denervated dogs. Arterial pressure did not
      decrease when continuous positive airway pressure was switched to PEEP. Plasma
      renin activity, aldosterone, and antidiuretic hormone concentrations were greater
      in normovolemic dogs. The PEEP increased aldosterone and antidiuretic hormone
      concentrations only in normovolemic dogs. CONCLUSIONS: In conscious dogs, renal
      nerves have no appreciable contribution to sodium and water retention during
      PEEP. Retention in normovolemic dogs seems to be primarily caused by an
      activation of the renin-angiotensin system and an increase in the antidiuretic
      hormone. Excretion rates depended on the volume status of the dogs.

PMID- 9778013
TI  - Isoflurane and sevoflurane induce vasodilation of cerebral vessels via ATP
      sensitive K+ channel activation.
AB  - BACKGROUND: Activation of adenosine triphosphate-sensitive K+ channels causes
      cerebral vasodilation. To assess their contribution to volatile anesthetic
      induced cerebral vasodilation, the effects of glibenclamide, an adenosine
      triphosphate-sensitive K+ channel blocker, on the cerebral vasodilation induced
      by isoflurane and sevoflurane were studied. METHODS: Pentobarbital-anesthetized
      dogs (n = 24) assigned to one of two groups were prepared for measurement of pial
      vessel diameter using a cranial window preparation. Each dog received three
      minimum alveolar concentrations (MAC; 0.5, 1, and 1.5 MAC) of either isoflurane
      or sevoflurane, and the pial arteriolar diameters were measured in the presence
      or absence of glibenclamide (10(-5) M) infused continuously into the window. Mean
      arterial pressure was maintained with phenylephrine. Furthermore, to assess the
      direct effect of isoflurane and sevoflurane on cerebral vessels, artificial
      cerebrospinal fluid was administered topically by being bubbled with isoflurane
      or sevoflurane. The blocking effect of glibenclamide on the vasoactive effects of
      these anesthetics also were evaluated. RESULTS: Isoflurane and sevoflurane both
      significantly dilated large (> or = 100 microm) and small (< 100 microm) pial
      arterioles in a concentration-dependent manner (6% and 10%, 3% and 8% for 0.5
      MAC; 10% and 19%, 7% and 14% for 1 MAC; 17% and 28%, 13% and 25% for 1.5 MAC).
      Glibenclamide attenuated the arteriolar dilation induced by these anesthetics
      (not significant in isoflurane). Topical application of isoflurane or sevoflurane
      dilated large and small arterioles both in a concentration-dependent manner. Such
      vasodilation was inhibited completely by glibenclamide. CONCLUSION: The
      vasodilation of cerebral pial vessels induced by isoflurane and sevoflurane
      appears to be mediated, at least in part, via activation of adenosine
      triphosphate-sensitive K+ channels.

PMID- 9778014
TI  - Differential immediate-early gene expression in ovine brain after cardiopulmonary
      bypass and hypothermic circulatory arrest.
AB  - BACKGROUND: This study determined the induction profiles of immediate-early genes
      in the ovine brain after cardiopulmonary bypass (CPB) and hypothermic circulatory
      arrest (HCA), and the effects of the noncompetitive N-methyl-D-aspartate
      antagonist, aptiganel, on immediate-early gene expression, neuronal necrosis, and
      functional outcome. METHODS: Cannulas were inserted into isoflurane-anesthetized
      neonatal lambs undergoing CPB. One group received 2.5 mg/kg intravenous
      aptiganel. Animals underwent 90 or 120 min of HCA at 16 degrees C, were rewarmed
      to 38 degrees C, and were weaned from CPB. One hour after CPB was discontinued,
      brain perfusion was fixed and removed for immunohistochemical analysis in one
      half of the animals. The other half survived 2 or 3 days before their brains were
      evaluated for neuronal degeneration. Data were analyzed using analysis of
      variance; P < 0.05 was considered significant. RESULTS: Cardiopulmonary bypass
      and HCA differentially induced c-Jun and Fos proteins in the hippocampal
      formation, with c-Jun expression increasing with the duration of HCA, whereas Fos
      protein expressions were greatest after 90 min of HCA. The c-Jun protein was
      expressed in all neurons except the dentate gyrus. The Fos proteins were
      expressed in all neurons, including the dentate gyrus. Neuronal necrosis was
      observed in CA1 (73%) and CA3 (29%) neurons but not in the dentate gyrus after
      120 min of HCA. Aptiganel completely inhibited c-Jun expression (P < 0.001) but
      not Fos, improved functional outcome, and attenuated neuronal necrosis (P <
      0.05). CONCLUSIONS: The c-Jun and c-Fos proteins are expressed differentially in
      hippocampal neurons after CPB and HCA. Expression of c-Jun is associated with
      neuronal necrosis, whereas Fos protein expression is associated with survival.
      Aptiganel inhibits c-Jun expression, attenuates neuronal necrosis, and improves
      outcome.

PMID- 9778015
TI  - Prolonged intercostal nerve blockade in sheep using controlled-release of
      bupivacaine and dexamethasone from polymer microspheres.
AB  - BACKGROUND: Previous work from the authors' group characterized a prolonged
      percutaneous blockade of the sciatic nerve in rats using bupivacaine
      dexamethasone microspheres. The goals of the current study are to examine the (1)
      efficacy of bupivacaine microspheres with and without dexamethasone for
      intercostal blockade in sheep; (2) scaling of dose and duration with a 100-fold
      increase in body size from rats to sheep; (3) local toxicity and adverse systemic
      reactions to bupivacaine microspheres with and without dexamethasone. METHODS:
      Intercostal blocks were performed percutaneously in sedated sheep. Sensory
      blockade was measured at repeated time points by absent flinch response to skin
      pinch. Plasma bupivacaine concentrations were measured using high performance
      liquid chromatography. Chest wall specimens were examined by light microscopy.
      RESULTS: The duration of intercostal blockade increased with bupivacaine dose for
      animals receiving from 8 to 80 mg/kg of microspheres with and without
      dexamethasone. At each dose, microspheres containing dexamethasone had a longer
      duration of block than microspheres without dexamethasone. From 8 to 80 mg/kg,
      the mean duration of block with bupivacaine-dexamethasone microspheres increased
      from 4 to 13 days. Plasma concentrations of bupivacaine remained 10-fold below
      the convulsive EC50 concentration for sheep. Chest wall histology showed a
      significant granulomatous reaction around bupivacaine microspheres but not around
      bupivacaine-dexamethasone microspheres. CONCLUSIONS: A single administration of
      bupivacaine-dexamethasone microspheres produces an effective chest wall analgesia
      of several days' duration. This may prove useful clinically for thoracic surgery
      or trauma.

PMID- 9778016
TI  - A primer for EEG signal processing in anesthesia.

PMID- 9778017
TI  - The Internet: a practical guide for anesthesiologists.

PMID- 9778018
TI  - Combined use of transesophageal echocardiography and basket catheter can prevent
      tumor embolism in a patient with renal cell carcinoma.

PMID- 9778019
TI  - General anesthesia for a patient with centronuclear (myotubular) myopathy.

PMID- 9778020
TI  - Transfusion-related acute lung injury (TRALI) complicating colectomy for
      ulcerative colitis.

PMID- 9778021
TI  - Secretion of dantrolene into breast milk after acute therapy of a suspected
      malignant hyperthermia crisis during cesarean section.

PMID- 9778022
TI  - The use of inhaled sevoflurane for endotracheal intubation in epiglottitis.

PMID- 9778023
TI  - Treatment of pulmonary embolism during cesarean section with recombinant tissue
      plasminogen activator.

PMID- 9778024
TI  - Prolonged loss of consciousness and elevated porphyrins following propofol
      administrations.

PMID- 9778026
TI  - Replacement of air by carbon dioxide.

PMID- 9778025
TI  - Partition coefficients of volatile anesthetics in aqueous electrolyte solutions
      at various temperatures.

PMID- 9778027
TI  - Adenosine-induced transient cardiac arrest for placement of endovascular stent
      grafts in the thoracic aorta.

PMID- 9778028
TI  - New double intrabronchial tube (Naruke tube) for tracheostomized patients.

PMID- 9778029
TI  - Pneumothorax during endoscopic extraperitoneal herniorrhaphy.

PMID- 9778030
TI  - Temperature of propofol does not reduce the incidence of injection pain.

PMID- 9778031
TI  - Temperature correction of the calculated alveolar oxygen tension.

PMID- 9778032
TI  - Activation of human herpesvirus 8 (HHV-8) thymidine kinase (TK) TATAA-less
      promoter by HHV-8 ORF50 gene product is SP1 dependent.
AB  - Human herpesvirus 8 (HHV-8) is a newly discovered virus closely associated with
      Kaposi's sarcoma and primary effusion lymphomas. When they occur in patients with
      AIDS, these B-cell lymphomas frequently harbor another human herpesvirus, Epstein
      Barr virus (EBV). To determine the molecular mechanisms of the regulation of
      early gene expression by the immediate-early gene products of HHV-8 and to assess
      possible molecular interactions between HHV-8 and EBV, we studied the regulation
      of the HHV-8 thymidine kinase (TK) promoter in cell lines harboring either or
      both viruses. The constitutive chloramphenicol acetyltransferase (CAT) activity
      of the TK promoter was low in all six cell lines tested. A putative immediate
      early gene product of HHV-8 ORF50, which is a homolog of EBV BRLF1, was cloned
      into an expression vector and tested for its transactivating capacity. In the
      presence of 12-O-tetradecanoyl-phorbol-13-acetate (TPA), the CAT activity of the
      TK promoter was increased 7- to 720-fold by cotransfection with the ORF50 clone
      in EBV-producing cell lines (Ramos/AW, P3HR-1, and BC-1) but not in EBV-negative
      cell lines (BCBL-1 and Ramos), nor in the latently EBV-infected cell line Raji.
      The TK promoter contains three consensus SP1- and two AP1-binding sites. In
      electrophoretic mobility shift assays, the cellular factor SP1, but not AP1, was
      found to bind specifically to the TK promoter. To determine whether the increased
      CAT activity resulted from the interaction of SP1 with the ORF50 gene product, we
      introduced mutations into two SP1-binding sites. Both mutated SP1 sites had
      reduced SP1-binding activity and greatly decreased TK promoter responsiveness to
      ORF50 transactivation, suggesting that upregulation of TK promoter by ORF50 is
      SP1 dependent.

PMID- 9778033
TI  - Thyroid hormone receptor is a negative regulator in p53-mediated signaling
      pathways.
AB  - Thyroid hormone nuclear receptors (TRs) are ligand-dependent transcription
      factors which regulate growth, differentiation, and development. The molecular
      mechanism by which TRs mediated these effects remains unclear. A prevailing
      hypothesis is that TRs exert their biological effects by cooperating with other
      transcription factors. We have recently shown that the human TR subtype beta1
      (hTRbeta1) interacts with the tumor suppressor p53, which plays a critical role
      in cell-cycle regulation and tumorigenesis. This interaction of hTRbeta1 with p53
      leads to an impairment of TR function. The present study examined whether
      hTRbeta1 could modulate the function of p53. Mapping of the domains of p53
      responsible for the interaction with hTRbeta1 indicated that the regions involved
      resided in the DNA-binding domain and carboxy terminus of p53. In agreement with
      this finding, hTRbeta1 increased the binding of p53 to p53 DNA-binding elements.
      This increase in DNA binding, however, resulted in repression of p53-dependent
      transcription activation in transfected cells. Furthermore, hTRbeta1 led to an
      inhibition of the p53-mediated induction of bax and gadd45 expression. In
      contrast, the p53-induced expression of p21 was not affected by hTRbeta1,
      suggesting that the expression of p53-regulated genes is differentially modulated
      by hTRbeta1. Because the expressions of bax, gadd45, and p21 are directly
      regulated by p53, these results indicate that hTRbeta1 can modulate p53-regulated
      gene expression and support the hypothesis that there is cross-talk between these
      two regulatory pathways. The cross-talk between these two transcription factors
      could play an important role in the biology of normal and cancer cells.

PMID- 9778034
TI  - Identification of human autoantigen La/SS-B as BC1/BC200 RNA-binding protein.
AB  - Rodent BC1 RNA and primate BC200 RNA are small cytoplasmic non-messenger RNAs
      that are phylogenetically unrelated. Nevertheless, the two RNAs exhibit a large
      degree of parallelism. In addition to some sequence similarities in their 3'
      domains, they are prevalently expressed in a similar subset of neurons and belong
      to a small group of transcripts with a somatodendritic location. Both RNAs are
      complexed with proteins as ribonucleoprotein particles (RNPs). Their similarities
      may even extend to analogous functional roles, for example, in the regulation of
      decentralized dendritic translation. To shed further light on the physiological
      role(s) of the BC1/BC200 RNPs, we began to analyze protein components that
      specifically bind to these RNAs. Ultraviolet-crosslinking experiments and
      affinity purification techniques revealed that the human autoantigen La/SS-B is
      associated with BC1/BC200 RNA in vitro and in vivo. As with other RNA polymerase
      III transcripts, La protein binds with high affinity to the 3' end of BC200 RNA.
      Our results suggest that an additional function of La may be control of dendritic
      translation by providing a link between the 5' Alu domain of BC200 RNP and the
      ribosome via the La protein dimer. The fact that La binds both BC1 and BC200 RNAs
      further supports the notion that the RNAs are functional analogs despite the fact
      that they arose from two separate retroposition events in two different mammalian
      lineages.

PMID- 9778035
TI  - Mouse prolactin receptor gene: genomic organization reveals alternative promoter
      usage and generation of isoforms via alternative 3'-exon splicing.
AB  - In rodents, the prolactin receptor is expressed as multiple isoforms with
      identical extracellular and membrane-proximal region sequences but with different
      3' sequences, encoding different cytoplasmic regions, and different 5'
      untranslated region (UTR) sequences. These divergent sequences could be the
      result of multiple prolactin receptor genes or of a single gene which displays
      alternative promoter usage and 3'-exon splicing. To investigate the molecular
      basis for these observations, we have cloned and determined the organization of
      the mouse prolactin receptor gene. Genomic DNA cloning allowed the arrangement of
      promoters 1A, 1B, and 1C to be determined. 5'-RACE-PCR from mouse liver
      identified two novel 5' prolactin receptor sequences, indicating that the gene
      has at least five different promoters, four of which are active in liver. The
      remaining nonvariable 5' UTR is encoded by a separate exon (exon 2), while a
      further 11 coding exons follow, the last 4 of which are alternatively spliced to
      produce the four isoforms of the receptor. Functional units were found to be exon
      specific. Thus, the multiple prolactin receptor isoforms are the product of a
      single gene of >120 kb which displays multiple promoter usage and 3'-exon
      splicing.

PMID- 9778036
TI  - Mouse cytochrome b561: cDNA cloning and expression in rat brain, mouse embryos,
      and human glioma cell lines.
AB  - A cDNA encoding cytochrome b561 has been isolated from a mouse brain cDNA
      library, which predicts a protein of 250 amino acids with a deduced Mr of 27,770.
      Northern blot analysis of different mouse and rat tissues revealed one major mRNA
      of 3300 bp, which is abundantly distributed in a number of neuroendocrine
      tissues. In addition, cytochrome mRNA levels in rat brain sections showed the
      highest distribution of cytochrome b561 in the hypothalamus, hippocampus,
      thalamus, and striatum, with a moderate level in the cerebral cortex, and the
      lowest levels in the olfactory bulb and cerebellum. Because non-neuronal cells in
      the central nervous system contained peptidyl alpha-amidating monooxygenase
      (PAM), to which cytochrome b561 donates its electrons, we used RT-PCR to document
      the coexpression of cytochrome b561 with PAM and dopamine beta-hydroxylase (DBH)
      in glioblastoma cells. Cytochrome b561 expression was detectable in the 11-day
      old mouse embryo, and the level of its mRNA increased tenfold by 15 and 17 days
      of gestation.

PMID- 9778037
TI  - Definition of family of coronin-related proteins conserved between humans and
      mice: close genetic linkage between coronin-2 and CD45-associated protein.
AB  - Cell adhesion and signal transduction are coordinated processes that may be
      linked through regulatory elements such as actin-binding proteins. One such
      protein that may fulfill this role is coronin. In Dictyostelium discoideum,
      coronin is involved in cellular processes such as mitosis, cell motility, and
      phagocytosis. In addition, a human coronin, p57, has been described which
      interacts with the p47 component of phox proteins and may be involved in the
      formation of phagocytic vacuoles. Here, we describe a family of four mouse
      proteins which share 38% identity with Dictyostelium coronin and thus are
      designated coronin-1, -2, -3, and -4. The gene for coronin-2 is localized to
      mouse chromosome 19, 5' of the gene for CD45-associated protein. All the coronin
      proteins contain five highly conserved WD domains. However, their carboxyl
      regions are quite distinct. Three of the four proteins are ubiquitously
      expressed, whereas coronin-1, the mouse ortholog of p57, demonstrates expression
      restricted to hematopoietic cells. Comparison of expressed sequence tag cDNAs
      indicates that coronin-1, -2, -3, and -4 are highly conserved between mice and
      humans.

PMID- 9778038
TI  - Deregulated expression of CDK2- or CDK3-associated kinase activities enhances c
      Myc-induced apoptosis.
AB  - Activation of high ectopic levels of c-Myc in serum-deprived Rat1-MycER cells by
      4-hydroxytamoxifen induces both proliferation and apoptosis. To further elucidate
      the role of G1 cyclin-dependent kinases (CDKs) in the process of Myc-induced
      apoptosis, we generated Rat1-MycER cells stably overexpressing CDK2 or CDK3.
      Ectopic expression of these CDKs in Myc-overexpressing cells was accompanied by
      upregulation of the specific kinase activities. Whereas neither high ectopic CDK2
      nor CDK3 alone induced apoptosis in serum-deprived Rat1 cells, both CDKs markedly
      elevated the incidence of Myc-induced apoptosis. It was shown earlier that in
      Rat1-MycER cells, which are resistant to tumor necrosis factor-alpha (TNF) when
      grown in high serum concentrations, the addition of TNF with the concomitant
      activation of Myc resulted in apoptotic cell death. Here, we show that neither
      CDK2 nor CDK3 induces susceptibility to the cytotoxic action of TNF in Rat1
      cells. However, both molecules heavily elevated the incidence of apoptosis
      induced by TNF together with Myc. It has earlier been reported that Myc-induced
      apoptosis in serum-deprived Rat1 fibroblasts is inhibited by specific cytokines,
      such as platelet-derived growth factor (PDGF). Here, we demonstrate that PDGF
      mediated protection from Myc-induced apoptosis is almost lost in Rat1 cells
      overexpressing CDK2 or CDK3. These apoptotic effects of CDK2 or CDK3 are not
      accompanied by alterations of proliferation parameters, such as DNA distribution,
      time the cells spend in each phase of the cell cycle, thymidine incorporation
      into DNA, or cell size analyzed during Myc-induced apoptosis. However, we found
      CDK3 to deregulate E2F-dependent transcription. In this report, we provide
      evidence for a not yet described property of CDK2 or CDK3 besides their activity
      in promoting proliferation: these G1-CDKs can promote apoptosis by interfering
      with the cell's response to survival factors.

PMID- 9778039
TI  - Regulation of mouse colony-stimulating factor-1 gene promoter activity by AP1 and
      cellular nucleic acid-binding protein.
AB  - Macrophage colony-stimulating factor (M-CSF; CSF-1) is a member of a complex
      network of cytokines that regulate monocytic cell development and activity. It is
      produced in nearly all organs by cell types commonly found in connective tissue,
      including fibroblasts and monocytes. Whether different cell types share common or
      have divergent mechanisms for regulating CSF-1 gene expression is not known. To
      address this question, the identity of cis-acting elements and cognate trans
      acting factors was characterized in a region of the CSF-1 promoter known to be
      more active in monocytes than in fibroblasts. The results of DNase I protection
      assays performed with fibroblast- or monocyte-derived nuclear extracts revealed a
      difference in the pattern of DNA-binding proteins. One protected region, common
      to both fibroblasts and monocytes, spans a putative phorbol ester-responsive
      element (TRE), and binding to the TRE by AP1 was verified with antibodies
      directed against c-fos and c-jun family members. Mutational analysis revealed
      that the TRE is required for CSF-1 gene expression in proliferating fibroblasts
      and monocytes. Binding of a second putative trans-acting factor, preferentially
      expressed in fibroblasts, to the region immediately upstream of the TRE was also
      detected. Screening a mouse expression library with oligonucleotides spanning the
      putative cis-acting element identified cellular nucleic acid-binding protein
      (CNBP) as the cognate binding activity, and antiserum to CNBP disrupted the
      electromobility shift assay complex. Mutational analysis revealed that loss of
      CNBP binding leads to a decrease in CSF-1 promoter activity in fibroblasts but
      has no effect on CSF-1 promoter activity in monocytes. Our results demonstrate
      that control of CSF-1 gene expression in monocytes and fibroblasts is mediated by
      common and cell type-specific trans-acting factors.

PMID- 9778041
TI  - Targeting the PML/RAR alpha translocation product triggers apoptosis in
      promyelocytic leukemia cells.
AB  - The t(15;17) rearrangement found in acute promyelocytic leukemia (APL) yields a
      fusion transcript, PML/RAR alpha. PML/RAR alpha expression is linked to
      leukemogenesis and to clinical sensitivity to all-trans retinoic acid (RA).
      Paradoxically, RA treatment causes transient complete remissions in most t(15;17)
      APL cases. The precise roles of PML/RAR alpha in triggering leukemia or in
      causing a maturation block are not yet known. This study explores directly these
      PML/RAR alpha functions in the growth and differentiation of APL cells using a
      hammerhead ribozyme to target PML/RAR alpha mRNA in the NB4 APL cell line. When
      the PML/RAR alpha cleaving but not the non-catalytic control ribozyme is
      introduced into the NB4 APL cell line, PML/RAR alpha protein expression is
      reduced. This catalysis signals growth suppression, cytotoxicity, and apoptosis
      without overcoming the maturation block found in these leukemic cells. These
      biologic effects depend on the selective pressure used to express the ribozyme
      from an episomal vector. Introduction of a non-catalytic, control ribozyme into
      NB4 cells caused no observed phenotype due to anti-sense activities. Expression
      of the catalytic or non-catalytic ribozymes in control cells lacking PML/RAR
      alpha mRNA yielded no apparent growth or differentiation effects. Thus, use of a
      hammerhead ribozyme that targets PML/RAR alpha expression in APL cells reveals
      the anti-apoptotic function of this translocation product and demonstrates that
      PML/RAR alpha cleavage is insufficient to overcome the differentiation block
      observed in these leukemic cells. Taken together, these findings indicate that
      persistent PML/RAR alpha expression is required to maintain basal leukemic cell
      growth and point to the therapeutic potential of targeting PML/RAR alpha in APL.

PMID- 9778040
TI  - Regulation of mouse Ah receptor (Ahr) gene basal expression by members of the Sp
      family of transcription factors.
AB  - The aromatic hydrocarbon receptor (AHR) is a ligand-activated transcription
      factor that regulates the expression of several drug-metabolizing enzymes and has
      been implicated in immunosuppression, teratogenesis, cell-specific hyperplasia,
      and certain types of malignancies and toxicities. The mouse Ahr gene 5' proximal
      promoter region, which contains four potential Sp1 motifs, is required for
      efficient basal expression. Using a fragment spanning the region from nt -174 to
      +70 of the Ahr promoter, we found that four regions corresponding to four Sp1
      sites were protected from DNase I digestion using nuclear extracts from MLE-12
      (lung), F9 (embryonal carcinoma), Hepa-1 (hepatoma), and 41-5a (epidermal) cells.
      The Hepa-1 and F9 cell lines were shown by reverse transcriptase-polymerase chain
      reaction and Western blot to contain mRNA and protein for Sp1 and Sp3, but not
      Sp2 and Sp4. In electrophoretic mobility shift assays using oligonucleotide
      probes corresponding to the four Ahr Sp1 sites, nuclear extracts from Hepa-1 and
      F9 cells formed complexes that were determined immunologically to contain both
      Sp1 and Sp3 protein. The two Ahr proximal Sp1 sites (A and B) were shown to bind
      both Sp1 and Sp3 proteins, whereas the more distal sites (C and D) bound only
      Sp1. Competition gel shift experiments showed that sites A and B had 10-fold
      higher affinity for Sp factors than did sites C and D. To determine the
      transactivation potential of each of the four Ahr Sp1 sites, we fused the Ahr
      promoter to a luciferase (LUC) reporter gene and transfected the construct into
      the Drosophila cell line Schneider-2, which contains no Sp1 or Sp1-like factors.
      Cotransfection of this construct with expression plasmids for each of the Sp
      factors revealed that Sp3 was approximately 1.6-fold more efficient than Sp1 in
      Ahr transactivation. Mutation of the four Sp1 sites individually and in
      combination demonstrated that each site contributes to the overall level of
      expression of the reporter gene and that interactions between these sites play a
      minor role in regulation of the Ahr-LUC construct. These results suggest that
      basal Ahr expression may be regulated by the expression and distribution of Sp1
      like factors.

PMID- 9778042
TI  - Sulindac sulfide inhibits Ras signaling.
AB  - The non-steroidal anti-inflammatory drug sulindac is used in cancer prevention
      and therapy, but the molecular aspects of its anti-tumor effect remain
      unresolved. In vivo the prodrug sulindac, is converted into the metabolite
      sulindac sulfide. We found that sulindac sulfide strongly inhibits Ras induced
      malignant transformation and Ras/Raf dependent transactivation. Sulindac sulfide
      decreases the Ras induced activation of its main effector, the c-Raf-1 kinase. In
      vitro sulindac sulfide directly binds to the Ras gene product p21ras in a non
      covalent manner. Moreover, we can show that sulindac sulfide inhibits the
      interaction of p21ras with the p21ras binding domain of the Raf protein. In
      addition, sulindac sulfide can impair the nucleotide exchange on p21ras by CDC25
      as well as the acceleration of the p21ras GTPase reaction by p120GAP. Due to its
      action at the most critical site in Ras signaling we propose sulindac sulfide as
      a lead compound in the search for novel anti-cancer drugs which directly inhibit
      Ras mediated cell proliferation and malignant transformation.

PMID- 9778043
TI  - Regulation of cell growth-dependent expression of mammalian CDC6 gene by the cell
      cycle transcription factor E2F.
AB  - CDC6 of Saccharomyces cerevisiae regulates the DNA replication initiation through
      the origin recognition complex (ORC). Identification of a human homolog of the
      CDC6 gene (HsCdc6) suggests a universal role of the gene product in DNA
      replication. Expression of HsCdc6 is growth-regulated. We investigated the
      molecular basis of growth-regulated expression of mammalian Cdc6. The promoter
      activity of isolated HsCdc6 upstream region was activated at late G1 and G1/S
      boundary in the cell cycle of rat embryonic fibroblast REF52 cells by the
      addition of serum. The isolated promoter was activated by exogenous expression of
      E2F without serum stimulation. However a mutant promoter lacking the E2F
      recognition sites failed to respond to serum stimulation and exogenous expression
      of E2F. Expression of endogenous Cdc6 was induced by exogenous expression of E2F.
      Therefore, we concluded that the growth-regulated expression of mammalian Cdc6
      was mediated by E2F. Moreover, we demonstrated that exogenous overexpression of
      either HsCdc6 or HsOrc1 failed to induce DNA synthesis unlike overexpression of
      E2F1, even though E2F1 induced both Cdc6 and Orc1, suggesting that E2F may
      regulate the expression of another gene(s), besides Cdc6 and Orc1, required for
      induction of cellular DNA synthesis in mammalian cells.

PMID- 9778044
TI  - Multiple negative elements contribute to repression of the HOX11 proto-oncogene.
AB  - The HOX11 proto-oncogene is normally expressed in embryogenesis where it directs
      the synthesis of the spleen. In adult tissues, HOX11 expression is silenced by an
      unknown mechanism. Aberrant expression of HOX11 occurs in T-cell acute
      lymphoblastic leukaemia (T-ALL), where it is thought to be involved in T-cell
      immortalization. The deregulated expression of HOX11 is frequently associated
      with chromosomal translocations which juxtapose a T-cell receptor (TCR) gene
      upstream of the HOX11 gene. In these cases, it is presumed that the activation of
      HOX11 expression results from bringing the gene under the control of TCR enhancer
      elements. However, activation of HOX11 also occurs in the absence of an
      associated translocation in both T-ALL and erythroleukaemia cells, implying that
      an alternative activation mechanism may exist. We hypothesized that HOX11 may be
      repressed in normal T-cells and erythroid cells by the action of negative
      elements which may be deleted or mutated in leukaemia. We therefore conducted a
      search for negative elements in the human HOX11 promoter which may function to
      silence its expression in normal cells of the haematopoietic lineages. Since
      little sequence of the HOX11 promoter was available, we began our investigation
      by sequencing over 4.5 kilobases of untranslated DNA from upstream of HOX11. The
      human sequence that overlaps with the 2.1 kb of murine Hox11 is highly conserved,
      suggesting that a large region of DNA upstream of HOX11 may have a regulatory
      function. We then used transfection assays to test the ability of portions of the
      promoter to drive transcription of a reporter gene. These studies identified four
      negative elements. Two of them (NRE2 and NRE4) function in all cell lines tested,
      while the remaining two (NRE1 and NRE3) appear to be cell-type specific. The DNA
      sequences of three elements are conserved between the human and mouse HOX11/Hox11
      promoters. We propose a model in which the combined action of these negative
      elements contributes to the overall repression of HOX11 expression in normal
      blood cells.

PMID- 9778046
TI  - Aberrant methylation of the BRCA1 CpG island promoter is associated with
      decreased BRCA1 mRNA in sporadic breast cancer cells.
AB  - BRCA1 mRNA is reduced in sporadic breast cancer cells despite the lack of
      mutations. Because a CpG island is found at the 5' end of the BRCA1 gene, we
      hypothesized that the decreased BRCA1 mRNA in sporadic breast cancer was
      associated with aberrant cytosine methylation of the CpG island. We examined
      BRCA1 mRNA expression in normal human mammary epithelial cells (HMECs),
      peripheral blood lymphocytes (PBLs) and six sporadic breast cancer cell lines
      using RT-PCR. The normal breast cells expressed high levels of BRCA1 mRNA. The
      sporadic breast cancer cell lines and PBLs expressed lower levels of BRCA1 mRNA
      ranging from a 3-16-fold decrease compared to the normal breast cells. We
      identified a 600 bp region of the BRCA1 CpG island that possessed strong promoter
      activity (approximately 40-fold above control), and determined the cytosine
      methylation patterns of the 30 CpG sites within this region by sodium bisulfite
      genomic sequencing. The HMECs, PBLs and five of the sporadic breast cancer cell
      lines were largely unmethylated. However, one sporadic breast cancer cell line,
      UACC3199, was > or = 60% methylated at all 30 CpG sites (18 sites were 100%
      methylated) and was associated with an eightfold decrease in BRCA1 mRNA compared
      to normal breast cells. These findings suggest that aberrant cytosine methylation
      of the BRCA1 CpG island promoter may be one mechanism of BRCA1 repression in
      sporadic breast cancer.

PMID- 9778045
TI  - Regulation of cytoskeletal association by a basic amino acid motif in polyoma
      virus middle T antigen.
AB  - The subcellular localization of many oncogenic proteins is thought to be
      important for their function. In the case of the middle T antigen of the DNA
      tumour virus, polyoma, localization to membranes in a specific manner is
      essential for its cellular transforming activity. To investigate factors that
      influence this localization, heterologous membrane targetting sequences were
      substituted for the middle T antigen transmembrane domain and the properties of
      the resulting proteins studied. Whereas C-terminal lipid modification derived
      from the H-ras CaaX box restored oncogenic activity to non-transforming truncated
      middle T antigen species, N-terminal myristylation from pp60c-src did not.
      Furthermore, a region, rich in basic amino acids and adjacent to the middle T
      transmembrane domain, was found to mediate association with detergent-insoluble
      cytoskeleton. Co-operation between the basic motif and neighbouring membrane
      binding domains resulted in specific localization of proteins to particular
      membrane sites, characterized by the association with subcellular structures,
      likely to be cytoskeletal in nature. These results demonstrate that the cellular
      localization of MT is regulated by at least two determinants, a transmembrane
      sequence which confers membrane binding and a basic motif which specifies a
      particular site within the membrane.

PMID- 9778047
TI  - Overexpression of AML1 renders a T hybridoma resistant to T cell receptor
      mediated apoptosis.
AB  - The AML1 gene, which encodes the DNA binding subunit of the heterodimeric
      transcription factor, PEBP2/CBF, is involved in several types of chromosomal
      translocations associated with human acute myeloid leukemia, and has been shown
      by gene targeting to be essential for the development of definitive hematopoiesis
      in the murine fetal liver. In addition, the gene is expressed abundantly in T
      lymphocytes and has been implicated in T cell specific gene expression. In the
      present study we examined the function of AML1 in T cell receptor (TCR)-mediated,
      Fas/Fas-ligand dependent apoptosis of a T hybridoma line, DO11.10. Several
      independent cell clones overexpressing the AML1 protein were isolated by
      transfecting AML1 cDNA into these cells. These clones possessed an increased
      level of PEBP2/CBF DNA binding activity and were found to be resistant to
      apoptosis induced by anti-CD3 antibody treatment. Northern blot analysis revealed
      that induction of the Fas-ligand transcript was markedly suppressed in the anti
      CD3 treated clones. Instead, expression of IL-2 receptor alpha subunit (IL-2R
      alpha), which is a manifestation of proliferative TCR signaling, was induced.
      This was in contrast to the parental, anti-CD3 treated DO11.10 cells where
      induction of Fas-ligand but not of IL-2R alpha was observed. Resistance of the
      AML1 overexpressing cell clones to TCR-mediated apoptosis is most likely
      attributable to the lack of Fas-ligand induction, since simultaneous treatment
      with anti-CD3 and anti-Fas antibodies caused apoptosis of the clones. The overall
      results suggest that the AML1 protein may play a pivotal role in switching TCR
      signaling between apoptosis and cell proliferation in T lymphocytes.

PMID- 9778048
TI  - A novel ionizing radiation-induced signaling pathway that activates the
      transcription factor NF-kappaB.
AB  - The signaling pathway through which ionizing radiation induces NF-kappaB
      activation is not fully understood. IkappaB-alpha, an inhibitory protein of NF
      kappaB mediates the activation of NF-kappaB in response to various stimuli,
      including cytokines, mitogens, oxidants and other stresses. We have now
      identified an ionizing radiation-induced signaling pathway that is independent of
      TNF-alpha. IkappaB-alpha degradation is rapid in response to TNF-alpha induction,
      but it is absent in response to ionizing radiation exposure in cells from
      individuals with ataxia-telangiectasia (AT). Overexpression of wild-type ATM, the
      product of the gene defective in AT patients, restores radiation-induced
      degradation of IkappaB-alpha. Furthermore, phosphorylation of IkappaB-alpha by
      immunoprecipitated ATM kinase is increased in control fibroblasts and transfected
      AT cells following ionizing radiation exposure. These data provide support for a
      novel ionizing radiation-induced signaling pathway for activation of NF-kappaB
      and a molecular basis for the sensitivity of AT patients to oxidative stresses.

PMID- 9778050
TI  - Genetic instability in the 9q22.3 region is a late event in the development of
      squamous cell carcinoma.
AB  - Squamous cell carcinoma (SCC) of the skin represents a group of neoplasms which
      is associated with exposure to UV light. Recently, we obtained data suggesting
      that invasive skin cancer and its precursors derive from one original neoplastic
      clone. Here, the analysis were extended by loss of heterozygosity (LOH) analysis
      in the chromosome 9q22.3 region. A total of 85 samples, taken from twenty-two
      sections of sun-exposed sites, corresponding to normal epidermis, morphological
      normal cells with positive immuno-staining for the p53 protein (p53 patches),
      dysplasias, cancer in situ (CIS) and squamous cell carcinomas (SCC) of the skin
      were analysed. Overall, about 70% of p53 patches had mutations in the p53 gene
      but not LOH in the p53 gene or 9q22.3 region. Approximately 70% of the dysplasias
      showed p53 mutations of which about 40% had LOH in the p53 region but not in the
      9q22.3 region. In contrast, about 65% of SCC and CIS displayed LOH in the 9q22.3
      region, as well as frequent (80%) mutations and/or LOH in the p53 gene. These
      findings strongly suggest that alterations in the p53 gene is an early event in
      the progression towards SCC, whereas malignant development involves LOH and
      alterations in at least one (or several) tumor suppressor genes located in
      chromosome 9q22.3.

PMID- 9778049
TI  - Retinoic acid-mediated growth arrest of EBV-immortalized B lymphocytes is
      associated with multiple changes in G1 regulatory proteins: p27Kip1 up-regulation
      is a relevant early event.
AB  - EBV-immortalized lymphoblastoid B cell lines (LCLs) are a suitable in vitro model
      for the study of EBV-related lymphoproliferative disorders of immunosuppressed
      patients. We have previously shown that 9-cis-, 13-cis- and all-trans-retinoic
      acid (RA) powerfully inhibit LCL proliferation at concentrations corresponding to
      therapeutically achievable plasma levels (10(-6) M). Herein we show that RA
      induced LCL accumulation in the G0/G1 phases correlated with the loss of the
      catalytic activity of all three G1-associated CDKs (CDK2, CDK4 and CDK6) and with
      increased levels of underphosphorylated pRb and, in some LCLs, p130. LCLs
      arrested in G0/G1 by RA also showed a significant decrease in the protein levels
      of cyclins D2, D3 and A, together with a reduction in the amount of cyclin D
      associated with CDK4 and CDK6, probably accounting for the inhibition of the
      relative kinase activity. In addition, RA-treated LCLs showed a marked up
      regulation of the CDK inhibitor (CKI) p27Kip-1 at the protein but not mRNA level,
      which correlated with a progressive increase of p27Kip-1 in CDK2 complexes (more
      than 2.5-fold) and with a reduction in the active phosphorylated form of CDK2.
      p27Kip-1 may also contribute to the inhibition of CDK4 kinase activity, as the
      amount of CDK4-associated p27Kip-1 was increased by 50% after RA exposure. p27Kip
      1 up-regulation stably persisted for more than one week after RA withdrawal
      concomitantly with the maintenance of the proliferative block. Moreover,
      neutralization of TGFbeta did not affect the growth inhibitory activity of RA,
      suggesting that LCL growth arrest induced by these retinoids is probably not
      mediated by a pathway directly involving TGFbeta. Overall, these results
      demonstrate that RA treatment of EBV-immortalized B lymphocytes is associated
      with multiple effects on G1 regulatory proteins, including p27Kip1 up-regulation,
      decreased levels of cyclins D2, D3 and A, and inhibition of CDK2, CDK4 and CDK6
      activity, which ultimately result in reduced pRb phosphorylation and G0/G1 growth
      arrest.

PMID- 9778052
TI  - Rho-regulated signals induce apoptosis in vitro and in vivo by a p53-independent,
      but Bcl2 dependent pathway.
AB  - Rho proteins are a branch of GTPases that belongs to the Ras superfamily which
      are critical elements of signal transduction pathways leading to a variety of
      cellular responses. This family of small GTPases has been involved in diverse
      biological functions such as cytoskeleton organization, cell growth and
      transformation, cell motility, migration, metastasis, and responses to stress. We
      report that several human Rho proteins including Rho A, Rho C and Rac 1, are
      capable of inducing apoptosis in different cell systems like murine NIH3T3
      fibroblasts and the human erythroleukemia K562 cell line. Since K562 cells are
      devoid of p53, apoptosis induced by Rho in this system is independent of p53. Rho
      dependent apoptosis is mediated by the generation of ceramides, and it is
      drastically inhibited by ectopic expression of Bcl2, both under in vitro and in
      vivo conditions. Furthermore, the human oncogenes vav and ost that have been
      shown to function as guanine exchange factors for Rho proteins, were also able to
      induce apoptosis under similar conditions. Finally, we also report that the
      levels of endogenous Rho proteins are increased when U937 myeloid leukemia cells
      are exposed to apoptosis-inducing conditions such as TNF alpha treatment.
      Furthermore, TNF alpha-induced apoptosis in these cells is inhibited by
      expression of a dominant negative mutant of Rac 1 but it is not affected by a
      similar mutant of Rho A. These results suggest that Rho proteins play an
      important role in the physiological regulation of the apoptotic response to
      stress-inducing agents.

PMID- 9778053
TI  - Genomic characterization of the human trkC gene.
AB  - The trkC gene encodes the high-affinity receptor for neurotrophin 3 and plays an
      important role in the regulation of the survival and differentiation of the
      mammalian nervous system and in heart development. Chromosomal rearrangements of
      trkC have been recently reported in congenital fibrosarcoma and it has been
      proposed that abnormal activation of this gene might be involved in tumor
      development. To facilitate the search for new mutations and rearrangements in the
      human trkC locus we have partially characterized its genomic organization by
      restriction mapping and have obtained the complete intron-exon structure. Our
      results show that human trkC consists of 20 exons, including two that encode the
      inserts present in the extracellular and tyrosine kinase domains, and another two
      that encode the carboxyl-terminal tail of the truncated TRKC isoform. Analysis of
      the 5' flanking region revealed the absence of TATA box, a very high content in
      C/G compatible with a CpG island and the presence of putative binding sites for
      the AP1, AP2, GC, ATF, BRN2, AML1 and Nkx2.5 transcription factors.

PMID- 9778051
TI  - Increased synthesis of phosphocholine is required for UV-induced AP-1 activation.
AB  - Exposure of mammalian cells to UV irradiation stimulates phosphatidylcholine
      hydrolysis and activates the transcription factor AP-1. Since phosphocholine
      (PCho), a phospholipid metabolite, is a potential regulator of mitogenesis and
      carcinogenesis, we examined the effect of UV exposure on the formation of PCho
      and the possible mediatory role of PCho in UVB-and UVC-induced activation of AP-1
      in mouse JB6 epidermal cells. We found that both UVB and UVC irradiation resulted
      in increased PCho levels. Hemicholinium-3 (HC-3), an inhibitor of choline kinase,
      strongly inhibited UV-induced AP-1 activity. By contrast, relatively low levels
      of PCho (80 microM) or choline (20 microM) nearly doubled UV-induced AP-1
      activity, while higher (2-20 mM) concentrations of PCho alone stimulated AP-1
      activity 6-8-fold. Importantly, HC-3 inhibited only the stimulatory effect of
      choline, but not of PCho, on AP-1 activity. Of the mitogen-activated protein
      (MAP) kinases involved in the regulation of AP-1 activity, UVC stimulated the MAP
      kinase family ERK-1/ERK-2, JNK as well as p38 kinase activity. These UVC effects
      were all inhibited by HC-3. With UVB, by contrast, only the activation of ERK
      1/ERK-2 was inhibited by HC-3. The data suggest that increased formation of PCho
      is required for UV-induced activation of AP-1 by an ERK-1/ERK-2-dependent
      mechanism.

PMID- 9778054
TI  - Active signaling by Neu in transgenic mice.
AB  - Transgenic mice engineered to overexpress the HER-2/neu/erbB-2 protooncogene
      under the control of a mammary-specific promoter develop mammary tumors and are a
      model for human breast cancer. Signal transduction by Neu was examined in situ in
      the tumors of these transgenic mice. This was accomplished using the PN2A
      monoclonal antibody, which recognizes Neu only in the phosphorylated, and
      therefore actively signaling, state. Immunohistochemistry using PN2A demonstrated
      that Neu actively signals in the tumors of Neu transgenic mice. Expression of Neu
      was always accompanied by co-overexpression of the endogenous epidermal growth
      factor receptor. Qualitatively similar results were found in mammary tumors from
      mice bitransgenic for the neu and transforming growth factor-alpha genes (both
      driven by the mouse mammary tumor virus promoter). Early mammary lesions
      demonstrated distinctive patterns of Neu activation relative to expression
      levels. Overexpression and activation were separable both temporally and
      spatially. These results refine the multi-step model for the role of Neu in
      mammary neoplasia and establish phosphorylation-state specific antibodies as a
      powerful tool for investigating tumor progression.

PMID- 9778055
TI  - Transgenic mouse model for skin malignant melanoma.
AB  - We report here on a novel metallothionein-I (MT)/ret transgenic mouse line in
      which skin melanosis, benign melanocytic tumor and malignant melanoma
      metastasizing to distant organs develop stepwise. The process of tumor
      development and its malignant transformation in this line may resemble that of
      the human giant congenital melanocytic nevus that is present at birth and that
      frequently gives rise to malignant melanoma during aging. We observed an increase
      in the expression level and activity of the ret transgene during the disease
      progression. That increase in transgene expression accompanied an activation of
      mitogen-activated protein kinases (MAPKs) and c-Jun as well as matrix
      metalloproteinases. These results suggest that progressive dysregulation of the
      expression level of the ret transgene might play a crucial role in the malignant
      transformation of melanocytic tumors developed in the MT/ret transgenic mouse
      line.

PMID- 9778056
TI  - Noninvasive risk stratification after myocardial infarction: which test is best?

PMID- 9778057
TI  - TIMI flow and surrogate end points: what you see is not always what you get.

PMID- 9778058
TI  - Caffeine ingestion: yet another wake-up call?

PMID- 9778059
TI  - Asymptomatic restenosis: should we (re)intervene? An unresolved dilemma.

PMID- 9778060
TI  - The stent decade: 1987 to 1997. Stanford Stent Summit faculty.
AB  - In January 1997, experts from the United States, Europe, and Japan gathered at
      Stanford University to review their collective experience with intracoronary and
      noncoronary stenting and to identify and prioritize issues requiring further
      clinical investigation. This report summarizes the discussions that took place
      during this stent summit. Knowledge of stent-tissue interaction from animal and
      human pathologic specimens was reviewed in the context of evolving stent designs.
      The relative merits of coil and slotted tubular stent designs were discussed.
      Stent deployment routines, including self-expansion, balloon expansion, and high
      pressure delivery were debated. The potential for covered stents and coated
      stents was explored. Problems surrounding the routine deployment of stents were
      identified: small vessel disease, long lesions, bifurcation stenoses, vein graft
      disease, ostial disease, left main stenoses, and intrastent restenosis. The value
      of intravascular ultrasound, as an adjunct to stenting, was explored and debated.
      An algorithm for "provisional stenting" based on ultrasound criteria was
      developed. Noncoronary stenting of the aorta, iliacs, and carotids were
      discussed. Clinical applications that may lead to randomized clinical trials were
      identified.

PMID- 9778061
TI  - Kissing stents in the aortic bifurcation.
AB  - BACKGROUND: We report the first series of simultaneously delivered stents used to
      treat stenosis of the aortic bifurcation. Surgical treatment of aortoiliac
      occlusive disease carries up to a 3% mortality rate. Percutaneous balloon
      techniques to treat aortic bifurcation stenosis, although safer, are still
      associated with up to a 9% incidence of dissection, thrombosis, or significant
      residual stenosis. Kissing stent insertion should decrease the incidence of these
      complications. METHODS: Twenty patients underwent kissing stent insertion.
      Suitable candidates included patients with symptoms of lower limb ischemia and
      significant atherosclerotic lesions in both ostial common iliac arteries (n = 15)
      or with extremely complex single ostial iliac stenoses (n = 5). Palmaz stents
      were delivered simultaneously to both limbs of the aortic bifurcation. RESULTS:
      Kissing stent insertion was successfully performed in all 20 patients without
      acute complications. Mean percent stenosis decreased from 46.2%+/-24.8% to 
      6.8%+/-13.3% (P = .0001) in the right iliac artery, 42.3%+/-22.8% to -1.6% +/
      18.1% (P = .0001) in the left iliac artery, and 19.1%+/-16.6% to 2.3%+/-16.4% (P=
      .0008) in the distal aorta. Intermittent claudication symptoms were improved in
      18 (95%) of 19 patients with 12 (63%) of 19 patients becoming totally
      asymptomatic. The strongest predictor of clinical outcome after kissing stent
      insertion was the preprocedural extent of femoropopliteal disease: 8 (89%) of 9
      patients with femoropopliteal narrowing <75% bilaterally became completely
      asymptomatic at follow-up compared with only 3 (30%) of 10 patients with more
      severe stenoses (P = .02). CONCLUSIONS: We have demonstrated in 20 patients that
      stenoses of the aortic bifurcation can be treated effectively with kissing stents
      with few serious adverse events.

PMID- 9778062
TI  - Late coronary artery stenting in patients with acute myocardial infarction.
AB  - BACKGROUND: The safety and efficacy of late coronary artery stenting of the
      infarct-related artery after acute infarction has not been evaluated previously.
      METHODS AND RESULTS: Coronary artery stenting was performed in 117 consecutive
      patients with acute infarction who were receiving ticlopidine/aspirin regimen
      without coumarin. There were 97 men and 18 women, aged 58+/-11 (mean +/- SD)
      years. A total of 136 Palmaz-Schatz stents were successfully implanted in 130
      lesions 15+/-8 days after acute myocardial infarction (median 9 days) in 115 of
      117 (98%) patients. The minimal luminal diameter (MLD) increased from 0.66+/-0.46
      to 3.14+/-0.53 mm (P< .001), with an acute gain of 2.49+/-0.61 mm. One patient
      had acute thrombosis requiring further stenting and another patient received
      emergency bypass surgery. There was no subacute thrombosis or other
      complications. During a follow-up duration of 14+/-3 months, 2 patients had
      angina pectoris develop and 1 died suddenly. Sixty-two patients underwent a
      follow-up coronary angiography 195+/-36 days after stenting. Restenosis was noted
      in 8 patients (13%); the MLD was 2.19+/-0.73 mm, the late loss was 0.96+/-0.65 mm
      (P< .001), the loss index was 0.39+/-0.28, and the net gain was 1.56+/-0.79 mm
      (P< .001). The angiographic left ventricular ejection fraction increased from
      47%+/-12% to 55%+/-12% (P< .001). CONCLUSIONS: Late coronary stenting of the
      infarct-related artery in patients with acute myocardial infarction is a safe and
      effective late reperfusion therapy and may be beneficial to the patients.

PMID- 9778063
TI  - Impact of routine angiographic follow-up after angioplasty.
AB  - BACKGROUND: There is an ongoing controversy as to whether repeat coronary
      angiography should be routinely performed after successful percutaneous
      transluminal coronary angioplasty (PTCA). METHODS: We examined the 10-year
      outcome in 400 patients who had or had not undergone an angiographic control 6
      months after successful PTCA and a subsequent event-free 6-month period. Our
      comparison was based on data gathered by questionnaire and telephone interview in
      315 patients with (group A) and 85 patients without (group B) a routine 6-month
      angiographic control. Multivariate analysis (Cox model) was performed to identify
      predictors of adverse events. RESULTS: During the 10-year follow-up period, 22
      (7%) of the 315 patients in group A died, compared with 16 (19%) patients in
      group B (P= .003). In groups A and B, respectively, acute myocardial infarction
      occurred in 28 (9%) and 10 (12%) patients (not significant [NS]); coronary artery
      bypass grafting (CABG) was performed in 42 (13%) and 14 (16%) patients (NS);
      repeat PTCA was performed in 89 (28%) and 11 (13%) patients (P= .012); and
      serious adverse events (death, myocardial infarction, CABG) occurred in 76 (24%)
      and 32 (38%) patients (P= .02). Absence of a 6-month angiographic follow-up was
      identified as an independent predictor of death associated with a 2.7 times
      higher mortality rate during the 10-year follow-up period. Previous myocardial
      infarction increased the risk of death 2.5 times. Any increase of residual
      diameter stenosis by 10% was combined with a 1.4 times higher mortality rate. The
      chance of bypass surgery was higher in patients with multivessel disease (2.9
      times), in patients with unstable angina (2.1 times), and in case of an increase
      of residual diameter stenosis by 10% (1.3 times). No predictor for the risk of
      myocardial infarction was found. Angiographic follow-up increased the likelihood
      of PTCA 2.5 times. CONCLUSIONS: A routinely performed angiographic control 6
      months after successful PTCA is associated with a significantly higher rate of
      repeat PTCA but, most important, is correlated with a significantly lower
      mortality rate during the 10-year follow-up period.

PMID- 9778064
TI  - Serum sialic acid concentration is not associated with the extent or severity of
      coronary artery disease in patients with stable angina pectoris.
AB  - BACKGROUND: Total serum sialic acid concentration has been reported to predict
      death from cardiovascular disease. This study was performed to assess the
      relation between serum sialic acid concentration and the angiographic extent and
      severity of coronary atheroma in patients with stable angina. METHODS:
      Quantitative coronary angiography was performed in 40 patients with stable angina
      with either triple-vessel disease (23 patients) or normal/nearly normal coronary
      arteries (17 patients). A colorimetric assay for the enzymatic determination of
      serum sialic acid was used. RESULTS: Serum sialic acid concentration was not
      significantly different in patients with normal or nearly normal coronary
      angiograms compared with those with triple-vessel disease (68+/-10 mg/100 mL and
      68+/-11 mg/100 mL, respectively). Neither was there any association between the
      extent or severity of coronary disease and serum sialic acid levels. CONCLUSIONS:
      Serum sialic acid concentration does not appear to be associated with the extent
      or severity of coronary artery disease in patients with stable angina pectoris.
      Thus the previously described association between serum sialic acid and
      cardiovascular death may reflect the role of mechanisms other than the severity
      of coronary artery narrowings.

PMID- 9778065
TI  - Effects of norepinephrine on the mechanical properties of the human radial artery
      in vitro.
AB  - BACKGROUND: The human radial artery has been proposed as an alternative to
      coronary grafts in subjects with coronary ischemic disease. Because this muscular
      artery is known to be prone to spasm, changes in its mechanical properties in
      response to catecholamines are important to investigate. METHODS: We describe a
      new echo-tracking technique of high resolution that allows investigation, in
      vitro, of the diameter and the wall thickness of arterial cylindrical segments.
      In addition, a classic tissue bath experiment is used to study the vasoreactivity
      of arterial rings. Mechanical properties of the radial artery are determined over
      a 0 to 200 mm Hg range of transmural pressure in the presence and absence of
      norepinephrine in the perfusion medium. RESULTS: With tissue bath experiments,
      the norepinephrine dose-response curve was characterized by an EC50 value of
      1.48+/-1.09 10(-6) mol/L and a maximal developed tension at 10(-5) mol/L. The
      results obtained with pressurized segments gave similar results with an EC50
      value of 8.1+/-2.3 10(-7) mol/L and a maximal change in diameter at 10(-5) mol/L
      norepinephrine. Under the influence of 10(-5) mol/L norepinephrine, the radial
      artery constriction reached 22%, significantly affecting the unstressed diameter.
      Compliance did not show any significant change in the overall transmural pressure
      range, whereas distensibility significantly increased and elastic modulus
      significantly decreased. CONCLUSION: The study shows that the capacitive
      properties of the human muscular radial artery are maintained with norepinephrine
      not only through decreased stiffness of wall material but also through reduced
      unstressed diameter. Thus drugs inducing smooth muscle relaxation may be helpful
      in preventing radial artery spasm after coronary grafts.

PMID- 9778066
TI  - Conversion efficacy and safety of repeated doses of ibutilide in patients with
      atrial flutter and atrial fibrillation. Study Investigators.
AB  - BACKGROUND: A study was conducted to determine the efficacy and safety of
      ibutilide fumarate versus placebo in the acute termination of atrial flutter and
      fibrillation. METHODS AND RESULTS: Two hundred sixty-two patients aged 28 to 88
      years with atrial flutter or fibrillation duration of 3 hours to 90 days were
      randomly assigned in a 5:1 ratio (ibutilide:placebo) to receive two 10-minute
      infusions, 10 minutes apart, of ibutilide (1 mg) or placebo. Patients were
      hospitalized and monitored by telemetry for 24 hours, with follow-up 72 hours
      later. Seventy-three (34.9%) of 209 evaluable ibutilide recipients had
      termination of atrial flutter or fibrillation within 1.5 hours compared with 0
      (0%) of 41 placebo recipients. Those with atrial flutter had a higher success
      rate. At hour 24, 86.3% remained in normal or alternative sinus rhythm. Of the
      patients who received ibutilide, 2.3% experienced drug-related sustained
      polymorphic or monomorphic ventricular tachycardia and recovered after
      intervention. Additionally, 7.3% experienced nonsustained polymorphic or
      monomorphic ventricular tachycardia. Other frequent medical events in ibutilide
      recipients were generally also noted in the placebo group. CONCLUSIONS: Ibutilide
      is effective and safe for acute termination of atrial fibrillation or atrial
      flutter.

PMID- 9778067
TI  - Acute effects of caffeine ingestion on signal-averaged electrocardiograms.
AB  - BACKGROUND: Although moderate caffeine ingestion has not been shown to be
      arrhythmogenic, caffeine toxicity can cause severe cardiac arrhythmias, including
      atrial fibrillation and ventricular tachycardia. Atrial fibrillation and
      ventricular tachycardia have been associated with prolongation of P-wave and QRS
      complex durations on signal-averaged electrocardiograms. This study investigated
      acute effects of caffeine ingestion on signal-averaged P-wave and QRS complexes.
      METHODS AND RESULTS: Signal-averaged electrocardiograms were obtained from 12
      normal subjects (6 men, 6 women; ages 21 to 26 years) before and after ingestion
      of caffeine (5 mg/kg body weight) or placebo in a randomized, double-blind,
      crossover fashion. Electrocardiograms for signal averaging were recorded from
      electrodes left in a constant location. After bandpass filtering (30 to 300 Hz)
      and amplification, signals were sampled over 7.2 minutes at 2000 Hz. Signal
      averaged P-wave and QRS complex durations did not significantly change after
      placebo ingestion. After caffeine ingestion QRS duration prolonged in 9 of 11
      subjects at 90 minutes (mean +/- SEM = 0.8+/-0.3 ms, P< .02) and in 8 of 9 after
      3 hours (1.1+/-0.2 ms, P< .001). No significant change in P-wave duration or
      heart rate was found after caffeine ingestion at any test interval. Average
      caffeine level in saliva 90 minutes after ingestion was 6.6+/-1.6 (SD) microg/dL.
      CONCLUSIONS: Although probably not arrhythmogenic in normal subjects, moderate
      caffeine ingestion does produce a small but statistically significant
      prolongation of signal-averaged QRS complexes. Further prolongation caused by
      excessive caffeine intake may be a factor in the genesis of arrhythmias
      associated with caffeine toxicity.

PMID- 9778068
TI  - Predictors of outcome after radiofrequency catheter ablation of the
      atrioventricular node for atrial fibrillation and congestive heart failure.
AB  - BACKGROUND: Although radiofrequency catheter ablation of the atrioventricular
      (AV) node is an established treatment for atrial fibrillation (AF) with
      uncontrolled ventricular response, factors that predict clinical outcome in
      patients with associated congestive heart failure (CHF) are unknown. METHODS AND
      RESULTS: AV node ablation and permanent pacemaker implantation was performed in
      44 consecutive patients (mean age 71+/-10 years) with CHF and AF associated with
      uncontrolled ventricular response. Immediately before ablation, mean left
      ventricular ejection fraction (EF) measured by 2-dimensional echocardiogram was
      34.6%+/-9.8%, mean exercise tolerance time was 2.6+/-1.8 minutes, and mean
      quality of life score was 62.3+/-19.7. Complete AV block was achieved in all 44
      patients but was complicated by death in 1 patient from cardiogenic shock soon
      after ablation. By 1 month after ablation, EF increased to 43.8%+/-13.7% (P <
      .01), exercise tolerance time was 4.0+/-2.5 minutes (P < .01), and mean quality
      of life score decreased to 35.6+/-18.1 (P < .01). Improved cardiac performance
      (increase in EF > or = 9% over baseline EF) was detected in 20 (45%) of the
      patients. During a mean follow-up of 17+/-9 months, 5 patients died suddenly of
      presumed ventricular tachyarrhythmia and 4 others died of progressive CHF.
      Multivariate Cox survival analysis identified baseline EF < or = 30%, presence of
      significant mitral regurgitation (>2+) before ablation, and failure to exhibit
      improved cardiac performance by 1 month after ablation as the only independent
      predictors of death. CONCLUSIONS: Baseline variables and failure of EF to improve
      soon after AV node ablation identifies patients with CHF and AF who have a high
      mortality rate. Adjunctive therapy to reduce sudden death and progressive heart
      failure should be evaluated in this subgroup.

PMID- 9778069
TI  - Comparison of oversensing during bradycardia pacing in two types of implantable
      cardioverter-defibrillator systems.
AB  - BACKGROUND: During bradycardia pacing in Ventritex Cadence (Models V-100 and V
      110) implantable cardioverter-defibrillators, amplifier gain is maximal and
      oversensing and false tachyarrhythmia detection have been reported. Newer
      Ventritex devices (Cadet, Model V-115 and Contour, Model V-145) have a modified
      automatic gain control that may minimize oversensing. METHODS AND RESULTS: We
      prospectively studied 50 patients (22 with Cadence, 28 with Cadet or Contour).
      Electrograms were evaluated for oversensing during bradycardia pacing. The
      bradycardia pacing refractory period required to prevent oversensing of T waves
      of paced beats and the time and number of beats required to achieve minimum gain
      after cessation of pacing were assessed. The bradycardia pacing refractory period
      could be left at its default setting of 350 ms in only 15 (30%) of 50 patients.
      The mean bradycardia pacing refractory period required to avoid oversensing of
      paced T waves was 386+/-32 ms. During pacing, oversensing of nonpaced T waves was
      seen in 12 (24%) devices, with similar incidence in Cadence devices (18%) and
      Cadet and Contour devices (29%, p = not significant). The time and number of
      beats to achieve minimum gain after pacing were longer in Cadence devices (19.0+/
      4.5 vs 4.6+/-1.2 sec; 21.3+/-3.3 vs 5.0+/-0.4 beats, both p < 0.001).
      CONCLUSIONS: The incidence of oversensing at maximum gain is similar in both
      types of devices, but more rapid changes in autogain levels in the newer devices
      may reduce the likelihood of false tachyarrhythmia detection.

PMID- 9778070
TI  - Abnormalities of the QT interval in primary disorders of autonomic failure.
AB  - BACKGROUND: Experimental evidence shows that activation of the autonomic nervous
      system influences ventricular repolarization and, therefore, the QT interval on
      the ECG. To test the hypothesis that the QT interval is abnormal in autonomic
      dysfunction, we examined ECGs in patients with severe primary autonomic failure
      and in patients with congenital dopamine beta-hydroxylase (DbetaH) deficiency who
      are unable to synthesize norepinephrine and epinephrine. SUBJECTS AND METHODS:
      Maximal QT and rate-corrected QT (QTc) intervals and adjusted QTc dispersion
      [(maximal QTc - minimum QTc on 12 lead ECG)/square root of the number of leads
      measured] were determined in blinded fashion from ECGs of 67 patients with
      primary autonomic failure (36 patients with multiple system atrophy [MSA], and 31
      patients with pure autonomic failure [PAF]) and 17 age- and sex-matched healthy
      controls. ECGs of 5 patients with congenital DbetaH deficiency and 6 age- and sex
      matched controls were also analyzed. RESULTS: Patients with MSA and PAF had
      significantly prolonged maximum QTc intervals (492+/-58 ms(1/2) and 502+/-61
      ms(1/2) [mean +/- SD]), respectively, compared with controls (450+/-18 ms(1/2), P
      < .05 and P < .01, respectively). A similar but not significant trend was
      observed for QT. QTc dispersion was also increased in MSA (40+/-20 ms(1/2), P <
      .05 vs controls) and PAF patients (32+/-19 ms(1/2), NS) compared with controls
      (21+/-5 ms(1/2)). In contrast, patients with congenital DbetaH deficiency did not
      have significantly different RR, QT, QTc intervals, or QTc dispersion when
      compared with controls. CONCLUSIONS: Patients with primary autonomic failure who
      have combined parasympathetic and sympathetic failure have abnormally prolonged
      QT interval and increased QT dispersion. However, QT interval in patients with
      congenital DbetaH deficiency was not significantly different from controls. It is
      possible, therefore, that QT abnormalities in patients with primary autonomic
      failure are not solely caused by lesions of the sympathetic nervous system, and
      that the parasympathetic nervous system is likely to have a modulatory role in
      ventricular repolarization.

PMID- 9778071
TI  - Differential effects of fosinopril and enalapril in patients with mild to
      moderate chronic heart failure. Fosinopril in Heart Failure Study Investigators.
AB  - OBJECTIVES: To investigate the efficacy and safety of fosinopril in the treatment
      of chronic heart failure (CHF), patients with mild to moderate CHF and left
      ventricular ejection fractions <40% were randomly assigned in a double-blind
      manner to receive fosinopril 5 to 20 mg every day (n = 122) or enalapril 5 to 20
      mg every day (n = 132) for 1 year. RESULTS: The event-free survival time was
      longer (1.6 vs 1.0 months, P= .032) and the total rate of hospitalizations plus
      deaths was smaller with fosinopril than with enalapril (19.7% vs 25.0%, P= .028).
      There was consistently better symptom improvement with fosinopril (P< .05). The
      incidence of orthostatic hypotension was lower in the fosinopril group (1.6% vs
      7.6%, P< .05). CONCLUSIONS: Fosinopril 5 to 20 mg every day was more effective in
      improving symptoms and delaying events related to worsening of CHF and produced
      less orthostatic hypotension than enalapril 5 to 20 mg every day.

PMID- 9778072
TI  - Heart failure after aortic valve replacement for aortic regurgitation:
      prospective 20-year study.
AB  - BACKGROUND: The objective of this study was to assess the probability of
      development of heart failure during a long-term follow-up in patients submitted
      for aortic valve replacement for aortic regurgitation on the basis of
      preoperative findings. METHODS AND RESULTS: Eighty-seven consecutive patients
      with pure aortic regurgitation and normal coronary arteries were submitted for
      aortic valve replacement and prospectively followed up. Clinical examination,
      echocardiography, and radionuclide ejection fraction were performed before
      surgery and at 1, 2, 5, and 10 years after surgery. Operative mortality rate was
      2.2% (2 patients). The follow-up period was 1 to 12 years (mean 6 years). Overall
      survival rate was 87% at 5 years and 81% at 10 years. During follow-up, 19
      patients had heart failure develop, and there were 14 deaths (6 caused by heart
      failure). Probability of heart failure was 16% at 5 years and 24% at 10 years.
      Age was the single independent preoperative predictor of both death and heart
      failure. Age >50 years (relative risk [RR] 10.4), preoperative ejection fraction
      <40% (RR 10.6), and end-systolic diameter >50 mm (RR 74) were independently
      related to the postoperative development of heart failure. CONCLUSIONS: Aortic
      valve replacement can be performed safely in patients with severe aortic
      regurgitation by following current recommendations. Age >50, end-systolic
      diameter >50 mm, and radionuclide ejection fraction <40% were independent
      preoperative predictors of postoperative heart failure. The only independent
      predictor of both postoperative death and heart failure was age >50 years.

PMID- 9778073
TI  - Diastolic effects of chronic digitalization in systolic heart failure.
AB  - BACKGROUND: The efficacy of short-term digitalization on exercise tolerance may,
      in part, reflect enhanced diastolic performance. However, cardiac glycosides can
      impair ventricular relaxation from cytosolic Ca++ overload. To detect any time
      dependent adverse effect, we assessed the diastolic function after long-term use
      of digitalis in patients with mild to moderate systolic left ventricular failure.
      METHODS AND RESULTS: From a cohort of 80 patients who received long-term,
      randomized, double-blind treatment with digitalis versus placebo at the WJB Dorn
      Veterans Affairs Medical Center, 38 survivors were evaluated at the end of follow
      up (mean 48.4 months) with evaluators blinded to treatment used. Each survivor
      underwent equilibrium scintigraphic and echocardiographic assessment of diastolic
      function. Peak and mean filling rates normalized with filling volume (FV),
      diastolic phase durations normalized with duration of diastole, and filling
      fractions were measured from the time-activity curve. The isovolumic relaxation
      period and ventricular dimensions were computed echocardiographically. By actual
      treatment-received analysis, treated versus untreated patients manifested a trend
      toward longer isovolumic relaxation (80.76 ms vs 61.54 ms, P = .06) but a
      markedly lower peak rapid filling rate (6.39 FV/sec vs 10.56 FV/sec, P = .02)
      despite comparable loading conditions. In addition, treated patients exhibited a
      lower mean rate of rapid filling (2.75 FV/sec vs 3.78 FV/sec, P = .05) in the
      absence of a longer rapid filling duration. However, the end-diastolic
      ventricular dimension did not differ between the 2 groups. Similar results were
      obtained by intention-to-treat analysis. Importantly, the mortality rate from
      worsening heart failure in the inception cohort was lower in the digitalis group
      versus the placebo group (P = .05) with no difference in total cardiac or all
      cause mortality. CONCLUSIONS: After long-term digitalization for systolic left
      ventricular failure, cross-sectional comparison with a control group from the
      same inception cohort shows a decrease in the rate and degree of ventricular
      relaxation. This effect did not interfere with the overall ventricular filling or
      with a favorable impact on outcome from worsening heart failure.

PMID- 9778075
TI  - Utilities for major stroke: results from a survey of preferences among persons at
      increased risk for stroke.
AB  - BACKGROUND: Patient beliefs, values, and preferences are crucial to decisions
      involving health care. In a large sample of persons at increased risk for stroke,
      we examined attitudes toward hypothetical major stroke. METHODS AND RESULTS:
      Respondents were obtained from the Academic Medical Center Consortium (n = 621),
      the Cardiovascular Health Study (n = 321 ), and United Health Care (n = 319).
      Preferences were primarily assessed by using the time trade off (TTO). Although
      major stroke is generally considered an undesirable event (mean TTO = 0.30),
      responses were varied: although 45% of respondents considered major stroke to be
      a worse outcome than death, 15% were willing to trade off little or no survival
      to avoid a major stroke. CONCLUSIONS: Providers should speak directly with
      patients about beliefs, values, and preferences. Stroke-related interventions,
      even those with a high price or less than dramatic clinical benefits, are likely
      to be cost-effective if they prevent an outcome (major stroke) that is so
      undesirable.

PMID- 9778074
TI  - Correlates of in-hospital cost among patients undergoing abdominal aortic
      aneurysm repair.
AB  - BACKGROUND: Surgical repair of abdominal aortic aneurysms (AAA) is increasingly
      being performed, but little is known about the correlates of in-hospital cost
      associated with this procedure. METHODS AND RESULTS: Baseline clinical
      characteristics, in-hospital outcomes, and total in-hospital costs were examined
      among a retrospective cohort of 71 patients who underwent AAA repair. Median age
      was 68 years, and 75% of the patients were men. High-risk characteristics for
      perioperative complications were common and included hypertension (73%),
      documented coronary artery disease (66%), smoking (60%), previous myocardial
      infarction (47%), history of congestive heart failure (12%), urgent or emergent
      AAA repair (16%), and diabetes mellitus (11%). Perioperative complications
      included congestive heart failure (13%), myocardial infarction (11 %), and death
      (1 %). Median length of stay in the surgical intensive care unit (SICU) was 2
      days (range 0 to 28), and median in-hospital stay was 9 days (range 5 to 39). In
      hospital cost for the 71 patients ranged from $13,766 to $82,435 (mean $25,931,
      median $21,633). Univariate and multiple linear regression analyses demonstrated
      that among the potential correlates investigated, number of SICU days (P= .007)
      and total length of stay (P< .0001) were the most closely associated with in
      hospital cost. CONCLUSIONS: Among patients undergoing AAA repair, the major
      correlates of in-hospital cost are the number of days spent in the SICU and the
      total number of days spent in the hospital. These results suggest that any
      intervention that reduces length of stay may significantly reduce the total in
      hospital cost associated with AAA repair.

PMID- 9778076
TI  - Validation of color Doppler measurements of minimum patent ductus arteriosus
      diameters: significance for coil embolization.
AB  - BACKGROUND: Echocardiography is sometimes performed to identify candidates for
      coil embolization of patent ductus arteriosus (PDA). Therefore we attempted to
      determine the validity of color Doppler echocardiography to accurately determine
      the minimum PDA diameter. METHODS AND RESULTS: We reviewed data from 27 children
      (median 3.8 years, range 1 to 15 years) with PDAs and measured their minimum
      ductal diameters by color flow Doppler echocardiography and by angiography. We
      found that there were significant mean differences between the color Doppler and
      angiographic measurements (2.7+/-0.8 vs 1.6+/-0.7 mm, P< .001) with color Doppler
      exceeding angiographic measurements by > or = 1.0 mm in 15 (56%) of 27 patients.
      More importantly, color Doppler measured a PDA > or = 4.0 mm (usually greater
      than that recommended for coiling) in 3 (11%) patients in whom the angiographic
      measurement was <4.0 mm. Correlation analysis demonstrated no correlation between
      the color Doppler and angiographic measurements (r2 = 0.17, P= .04, SEE = 0.2
      mm). CONCLUSIONS: These data suggest that color Doppler echocardiography often
      overestimates the true minimum PDA diameter, therefore we recommend that a color
      Doppler-based recommendation that a PDA is too large for transcatheter coil
      occlusion not be used exclusively to exclude a patient from this treatment
      modality.

PMID- 9778077
TI  - Doppler pressure half-time method of assessing mitral valve area: aortic
      insufficiency does not adversely affect validity.
AB  - OBJECTIVES: This study evaluated the effect of aortic insufficiency on the
      correlation of pressure half-time-derived mitral valve area with each of 2
      standards for mitral valve area (planimetry and cardiac catheterization) in a
      prospectively assembled cohort of patients scheduled for percutaneous balloon
      mitral commissurotomy. BACKGROUND: Although Doppler pressure half-time has been
      validated as a method for assessing mitral valve area, most previous studies have
      suggested that this noninvasive technique overestimates mitral valve area in the
      setting of coexistent aortic insufficiency. METHODS AND RESULTS: Echocardiography
      and cardiac catheterization were performed on 212 consecutive patients scheduled
      for percutaneous balloon mitral commissurotomy. After excluding 35 patients who
      did not have aortography, the rest were divided into a "no aortic insufficiency
      [AI] group" (n = 146) including those with trivial or no aortic insufficiency at
      catheterization and an "AI group" (n = 31 ) including those with mild or moderate
      aortic insufficiency. The pressure half-time mitral valve area tended to slightly
      underestimate invasive valve area by 0.04 cm2 in the AI group and to slightly
      overestimate invasive valve area by 0.06 cm2 in the no AI group. This difference
      between the groups was not statistically significant (P = .13). The pressure half
      time mitral valve area tended to underestimate planimetered valve area by 0.11
      cm2 in the AI group and by 0.10 cm2 in the no AI group. There was no difference
      between the 2 groups (P = .94). Potential confounders that could theoretically
      mask the effect of aortic insufficiency on the pressure half-time (including age,
      heart rate, blood pressure, left ventricular diastolic pressure, ejection
      fraction, mitral regurgitation, and atrial fibrillation) were excluded by
      multivariable analyses. CONCLUSIONS: The pressure half-time method of determining
      mitral valve area is not adversely affected by mild to moderate aortic
      insufficiency. This finding has implications for the utility of this technique in
      the rheumatic valvular disease population, in which mitral and aortic valve
      disease frequently coexist.

PMID- 9778079
TI  - Influence of risk factors on peripheral and cerebrovascular disease in men with
      coronary artery disease, low high-density lipoprotein cholesterol levels, and
      desirable low-density lipoprotein cholesterol levels. HIT Investigators.
      Department of Veterans Affairs HDL Intervention Trial.
AB  - BACKGROUND: The Veterans Administration-HDL Intervention Trial is an ongoing, 20
      center, randomized, double-blind, placebo-controlled study aiming to assess the
      effect of gemfibrozil-improved low high-density lipoprotein cholesterol levels on
      cardiovascular morbidity and mortality rates. METHODS AND RESULTS: Eligible
      patients were men with low high-density lipoprotein cholesterol levels and
      demonstrable coronary heart disease. A total of 2531 patients (average age 63.5
      years) were randomly assigned in this study, with a mean high-density lipoprotein
      cholesterol level of 0.83 mmol/L (32 mg/dL) and low-density lipoprotein
      cholesterol level of 2.87 mmol/L (111 mg/dL). Baseline data provided the
      opportunity to assess the interaction of several coronary heart disease risk
      factors and comorbid vascular diseases. Of these patients, 206 had diabetes
      mellitus (DM) alone, 1021 had hypertension (HTN) alone, 421 had both DM and HTN,
      and 883 had neither ("others"). Considering the influence of these risk factors
      on comorbidities independent of smoking status, patients with DM alone had a 2
      fold increase in the prevalence of peripheral vascular disease and a 1.5-fold
      increase in congestive heart failure. Patients with HTN had a significant
      increase in the prevalence of cerebrovascular disease, stroke, and congestive
      heart failure. Patients with HTN and DM had a significant increase in all
      comorbidities. Smoking resulted in substantial increase of both peripheral
      vascular disease and cerebrovascular disease. Compared with nonsmoking patients
      with no DM or HTN, patients with DM and HTN and smoking had a 3-fold increase in
      the prevalence of peripheral vascular disease and a 3.5-fold increase in
      cerebrovascular disease (P < .001). CONCLUSIONS: We conclude that DM is a strong
      correlate of peripheral vascular disease, hypertension of cerebrovascular
      disease, and that there is a strong additive effect between DM, HTN, and smoking
      on both.

PMID- 9778078
TI  - Comparison between 2-dimensional echocardiography and myocardial perfusion
      imaging in the emergency department in patients with possible myocardial
      ischemia.
AB  - BACKGROUND: Accurate identification of patients at high risk for acute coronary
      syndromes among those seen in the emergency department (ED) with possible
      myocardial ischemia and nonischemic electrocardiograms is problematic. Both 2
      dimensional echocardiography and myocardial perfusion imaging with technetium-99m
      sestamibi can identify patients at low and high risk; however, comparative
      studies are lacking. METHODS AND RESULTS: Patients initially considered at low or
      moderate risk for myocardial ischemia on the basis of the presenting history,
      physical examination, and electrocardiogram underwent both echocardiography and
      myocardial perfusion imaging within 4 hours of ED presentation. Positive
      echocardiography was defined as the presence of segmental wall motion
      abnormalities or moderate to severe global systolic dysfunction; positive
      perfusion imaging was defined as a perfusion defect in association with abnormal
      wall motion, thickening, or both. End points included MI, percutaneous
      transluminal coronary angioplasty, and positive stress perfusion imaging. Both
      imaging procedures were performed in the ED on 185 patients. Six patients had MI,
      and an additional 4 patients underwent percutaneous transluminal coronary
      angioplasty. Echocardiography and perfusion imaging were positive in all 10.
      Overall agreement between the 2 techniques was high (concordance 89%, kappa
      coefficient 0.74) in the 27 patients who had MI or underwent coronary
      angiography. For all patients, concordance was 89%, with a kappa coefficient of
      0.66. CONCLUSIONS: Agreement between echocardiography and perfusion imaging with
      technetium-99m sestamibi is high when used in patients in the ED with possible
      myocardial ischemia. Both techniques identified patients at high risk who
      required admission and those who could be safely discharged directly from the ED.

PMID- 9778080
TI  - An angiographic assessment of alteplase: double-bolus and front-loaded infusion
      regimens in myocardial infarction. DouBLE Study Investigators. Double Bolus Lysis
      Efficacy.
AB  - BACKGROUND: This study was designed to investigate the efficacy of alteplase
      double-bolus dosing compared with the front-loaded 90-minute infusion regimen in
      patients with acute myocardial infarction. Recent pilot studies have suggested
      that bolus dosing may provide improved efficacy in establishing early, complete,
      and sustained patency of the infarct-related artery in the thrombolytic treatment
      of acute myocardial infarction. METHODS AND RESULTS: In this multicenter,
      randomized, open-label trial, 461 patients with acute myocardial infarction
      received 100 mg alteplase as a front-loaded 90-minute infusion (15 mg bolus, then
      50 mg over a 30-minute period, then 35 mg over a 60-minute period) or double
      bolus (two 50 mg bolus injections 30 minutes apart). All patients also received
      intravenous heparin and oral aspirin during and after alteplase treatment. The 90
      minute angiographic patency rates were 74.5% in the double-bolus group and 81.4%
      in the infusion group (p = 0.08). Patency rates were also comparable for the two
      groups at 60 minutes (76.8% vs 77.5%) and 24 hours (95.5% vs 93.5%) after
      initiation of treatment. In-hospital mortality rates were 4.5% in the bolus group
      and 1.3% in the infusion group (p = 0.04); 30-day mortality rates were 4.5% and
      1.7%, respectively (p = NS). The two-groups were comparable in frequency of all
      other adverse events. CONCLUSIONS: Double-bolus alteplase administration produced
      reperfusion rates comparable to front-loaded infusion, but in-hospital and 30-day
      mortality rates were higher in the double-bolus group. These findings are in
      agreement with those of the COBALT megatrial, which also reported a trend to
      higher mortality rates with double-bolus dosing.

PMID- 9778081
TI  - HOT MI pilot study. Hyperbaric Oxygen and Thrombolysis in Myocardial Infarction.

PMID- 9778082
TI  - Dynamic QT dispersion during exercise.

PMID- 9778083
TI  - Role and significance of coagulation markers in understanding and treating acute
      coronary syndromes. Introduction.

PMID- 9778084
TI  - Coagulation markers and outcomes in acute coronary syndromes.

PMID- 9778085
TI  - Pathobiology of thrombin in acute coronary syndromes.

PMID- 9778086
TI  - Glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: pathophysiologic
      foundation and clinical findings.
AB  - The pathophysiologic basis for potent platelet inhibition in the acute coronary
      syndromes has been established. In the setting of PTCA for unstable angina and
      non-Q-wave myocardial infarction, there are clear data for a benefit of GP
      IIb/IIIa inhibition, whereas for primary PTCA in evolving myocardial infarction,
      preliminary data are very encouraging and a large-scale clinical trial is nearly
      completed. Glycoprotein IIb/IIIa inhibition as an adjunct to medical therapy for
      unstable angina is also the subject of encouraging preliminary data, and 3 large
      scale clinical trials have just been completed. Preliminary data have also been
      accrued for GP IIb/IIIa inhibition as conjunctive therapy with thrombolytic
      agents, and large clinical trials are now commencing.

PMID- 9778087
TI  - Relation between inhibition of platelet aggregation and clinical outcomes.
AB  - Despite a clinical trials experience in excess of 30,000 randomized patients,
      there is no definitive answer or agreement as to the relation between the level
      of inhibition of platelet aggregation and clinical outcome. Work with abciximab
      in the setting of percutaneous intervention would suggest that a level of
      platelet inhibition in excess of 80% provides the most favorable clinical
      benefit. Whether this applies to the small molecule inhibitors such as
      eptifibatide, tirofiban, and lamifiban is unknown and will require testing of the
      hypothesis in large-scale clinical trials. In the acute coronary syndromes, only
      the peptide and nonpeptide inhibitors have been studied independent of a need for
      percutaneous intervention. The level of platelet inhibition required to achieve
      maximal clinical benefit is unknown and awaits data from the large-scale unstable
      angina and myocardial infarction trials. Issues of combining heparin with GP
      IIb/IIIa inhibition and the platelet-altering effects of thrombolysis must be
      considered when examining what might be the optimal level of platelet inhibition
      that provides maximal efficacy while maintaining safety. Long-term therapy with
      the oral platelet inhibitors poses a particular challenge in determining an
      optimal level of treatment that renders clinical effectiveness while preserving
      safety. Large, ongoing clinical trials with these agents should provide insight
      into this question. Finally, given the complexity of using such potent therapies
      in any individual patient, there is a need for improved monitoring of the
      platelet inhibitory effect. Standard platelet aggregometry has its problems and
      limitations, as described, and is not a test that has wide-scale applicability.
      Whole blood aggregometry and other methods of rapidly assessing platelet function
      at the point of care have promise in this arena. In a clinical trial, such
      technology might allow better delineation of the population's pharmacodynamic
      response to an agent because it could be more widely applied and therefore more
      patients would be studied. In clinical practice, patients could be dosed
      individually so that a range of platelet inhibition could be achieved that was
      believed to provide optimal benefit and safety.

PMID- 9778088
TI  - Progress in point-of-care laboratory testing for assessing platelet function.

PMID- 9778089
TI  - The future of antithrombotic and antiplatelet therapy for ischemic heart disease.

PMID- 9778091
TI  - Physical activity and body composition: what do the national surveys reveal?
AB  - Measures of height, body weight, waist and hip girths are available from the
      Allied Dunbar National Fitness Survey and have been used to explore differences
      between respondents reporting differing levels of habitual physical activity.
      Body mass index (BMI), waist-to-hip ratio (WHR) and waist-to-height ratio were
      derived. Physical activity was estimated from a structured interview. The
      questionnaire permitted a separate estimate of levels of participation in
      vigorous and moderate intensity activity, as well as total energy expenditure.
      Each index of body composition was regressed against the measures of physical
      activity and other lifestyle factors. Relationships between activity and body
      composition measures were weak with different patterns emerging for men and
      women. These data suggest that it is doubtful whether changes in body composition
      brought about by interventions to increase population levels of physical activity
      will be revealed by measuring BMI. However WHR and waist-to-height ratio indices
      reflecting the bulk of the intra-abdominal fat stores may prove more informative.

PMID- 9778090
TI  - US weight guidelines: is it also important to consider cardiorespiratory fitness?
AB  - BACKGROUND: The health consequences of weight ranges across low to moderate and
      high levels of cardiorespiratory fitness are unknown. OBJECTIVE: To evaluate the
      validity of the 1995 US weight guidelines, while considering cardiorespiratory
      fitness. METHODS: We followed 21,856 men, aged 30-83 y, who had a complete
      preventive medical examination, including a maximal treadmill exercise test and
      body composition assessment. There were 427 deaths (144 cardiovascular disease
      (CVD); 143 cancer; 140 others) during an average of 8.1 y of follow-up. We used
      Cox proportional hazards regression to examine the relations among
      cardiorespiratory fitness, body mass index (BMI, kg/m2), and all-cause and CVD
      mortality. RESULTS: After adjustment for age, examination year, cigarette smoking
      and alcohol intake, we observed that men with a BMI of 19.0 to < 25.0 and who
      were unfit had 2.3 times the risk of all-cause mortality (95% confidence interval
      (95% CI), 1.59-3.17, P < 0.001) compared with fit men in this BMI group
      (reference category). Unfit men with a BMI of 25.0 to < 27.8 also had a greater
      risk of all-cause mortality than fit men in the same BMI category. Fit but
      overweight men (BMI > or = 27.8) had a similar rate of all-cause mortality as
      physically fit men of normal weight (BMI 19.0 to < 25.0) and had a lower risk of
      all-cause mortality than unfit and normal weight men. Fit men of normal weight
      had the lowest CVD mortality, while unfit and overweight men experienced the
      highest CVD mortality. Unfit men had substantially higher CVD mortality than fit
      men in each BMI group. CONCLUSIONS: Unfit men had higher all-cause and CVD
      mortality than fit men. The health benefits of normal weights appear to be
      limited to men who have moderate or high levels of cardiorespiratory fitness.
      These data suggest that the 1995 US weight guidelines may be misleading unless
      cardiorespiratory fitness is taken into account.

PMID- 9778092
TI  - Fit, fat and fat free: the metabolic aspects of weight control.
AB  - This paper examines the role of energy expenditure, especially physical activity
      related energy expenditure, in the metabolic aspects of body weight regulation.
      New data have emerged from studies conducted over the last decade, demonstrating
      that physical activity is a critical factor contributing to successful body
      weight regulation in lean and obese individuals. A growing number of prospective
      studies show the protective role of increased physical activity against weight
      gain over time. Also, individuals who are successful in long-term maintenance of
      a weight reduction are highly likely to also be physically active. Participation
      in physical activity is among the best predictors of success in weight
      maintenance. Physical activity facilitates weight maintenance through direct
      energy expenditure and improved physical fitness. The latter facilitates the
      amount and intensity of daily activities. Both components are of importance in
      relation to energy and substrate balance. Exercise may act as a substitute for an
      enlarged fat mass, in bringing about rates of fat oxidation commensurate with fat
      intake. Metabolic effects on lipid mobilization and oxidation and
      morphological/biochemical changes in the muscle fiber, contribute to this
      successful regulation of body weight. A limited number of studies indicate that,
      the minimal level of additional energy expenditure by physical exercise required
      for protection against gain in excessive body fatness, is around 12 kcal/kg body
      weight/d. In conclusion, the amount of energy expended in physical activity,
      mediated by several metabolic factors, may play an important role in body weight
      regulation.

PMID- 9778093
TI  - Effects of exercise on appetite control: loose coupling between energy
      expenditure and energy intake.
AB  - The relationship between physical activity and energy intake (food consumption)
      can take a number of forms, depending on the intensity, duration and frequency of
      the activity, and upon the degrees of fitness and physiological status of the
      individual. At extremes of energy expenditure such as those found in long
      distance cyclists, voluntary energy intake may be sufficient to balance the
      enormous daily expenditure; this is due to an entraining effect. Under more
      normal situations, there is a widely held belief that physical activity is a poor
      strategy for losing weight, since the energy expended drives up hunger and food
      intake to compensate for the energy deficit incurred. Recent studies in both
      normal weight and obese individuals show that substantial periods of exercise do
      not increase hunger and do not drive up food intake. Comparisons between
      sedentary and normally active individuals, or between enforced periods of rest or
      strenuous activity, generate little or no effect on levels of hunger or daily
      energy intake, indicating a rather loose physiological coupling between energy
      expenditure and food intake. This view generates an optimistic view of the role
      of exercise in weight loss and weight control, as it indicates that intake is not
      automatically driven up to compensate for energy expended. Reasons why physical
      activity often produces disappointing effects, rise from inappropriate food
      choices, a desire for self-reward after exercise and misjudgements about the
      relative rates at which energy can be expended (by exercise) or taken in (by
      eating). This means that physical activity will be most beneficial for weight
      control, if carried out in conjunction with a low energy dense diet or with
      judicious control of eating.

PMID- 9778094
TI  - The assessment of physical activity in individuals and populations: why try to be
      more precise about how physical activity is assessed?
AB  - Simple epidemiological measures of physical activity have proved sufficient to
      demonstrate associations with many chronic disease outcomes, but they have
      infrequently separated physical activity into its different dimensions, nor have
      they allowed estimation of dose-response effects. Generating greater clarity
      about the nature of the exposure-disease relationship, is an important step in
      the development of an appropriate public health intervention. This clarity can
      only be achieved with reliable and valid measurement instruments, which
      objectively and quantitatively assess the dimension of physical activity that is
      of interest for a particular health outcome. Objective techniques, such as heart
      rate monitoring, which have been directly compared to gold standard assessment
      methods, may be of use in medium-sized epidemiological studies and as a
      validation tool for questionnaires to be used in larger studies. The combination
      of methods with uncorrelated error, would result in an improved estimation of the
      true exposure and is an important area for research. Improved assessment would be
      of use in aetiological studies, in tracking trends in physical activity within
      populations, making objective comparisons between populations and in monitoring
      the effect of interventions.

PMID- 9778095
TI  - Motivation for physical activity and weight management.
AB  - The importance of exercise for health and long-term weight management is now well
      established. However, the critical challenge is facilitating increased physical
      activity in the large sector of young to middle-aged adults who are sedentary and
      already overweight. The psychology of exercise initiation and adherence in the
      overweight is seriously under-researched. However, it is possible to infer
      findings from the general population and from other health behaviours to develop
      effective exercise promotion strategies. Motivation and barriers to exercise,
      exercise-related beliefs, attitudes, and self-efficacy, and the formulation of
      self-perceptions and identity towards exercise need to be considered in
      interventions and campaigns to capture the interests of the general public.
      Readiness to change and behaviour change strategies need to be considered and
      incorporated into social support structures to facilitate individual behaviour
      change. This could be delivered through community, workplace and primary health
      care settings.

PMID- 9778096
TI  - National campaigns to promote physical activity: can they make a difference?
AB  - Mass media campaigns are one of the interventions used in health promotion, to
      stimulate population-level changes in behavior. A review of the literature found
      only three studies concerned with the effectiveness of national health promotion
      campaigns that used the mass media to promote physical activity. These showed
      that campaigns could help to change levels of knowledge and attitudes towards
      physical activity, but had limited short-term impact on physical activity
      participation. Reviews of the role of mass media in other health topics, also
      showed limited evidence of short-term behaviour change. The important broader
      role of campaigns is influencing the climate of public opinion in favour of
      health promoting public policies and providing an overall framework or umbrella
      under which a broader range of health promotion initiatives can take place. In
      particular, they appear to be useful to professionals working at a community
      level, as they provide the backdrop for more detailed community-level or
      interpersonal interventions.

PMID- 9778097
TI  - Promoting physical activity: issues in primary health care.
AB  - In the past few years, alliances between primary care and leisure services have
      become a popular strategy for exercise promotion in the England. 'GP Referral
      Schemes' typically involve referral to a local leisure centre by a General
      Practitioner (GP), whereupon patients are inducted into a 10-12 week exercise
      programme at a reduced fee. Referred patients are usually white, middle aged and
      apparently healthy women, with the main reason for referral being overweight. The
      schemes are characterised by their lack of formal evaluation, making conclusions
      about effectiveness impossible. In the US, physicians advice to exercise has been
      the focus of interventions to date. Two controlled trials, one randomised, have
      provided some evidence that exercise behaviour can be changed, at least in the
      short term. The ability to recruit sufficient numbers of patients, who have
      potentially the most to gain from increased physical activity, is the biggest
      barrier to primary care based interventions. One contributing factor to this
      problem, may be doctors and nurses' knowledge about the benefits of physical
      activity.

PMID- 9778098
TI  - The commercial sector: marketing diet and fitness responsibly.
AB  - The commercial sector, through a range of products and services, is already
      heavily involved in the weight loss industry. Because of its capability to access
      millions of people, it has great potential for promoting public health through
      dietary and exercise practices. However, an absence of controls or advertising
      standards, safety and quality, currently threatens its credibility. This paper
      draws from my own experience developing a now well-established diet and fitness
      organisation. It makes the case that the best quality products and practice arise
      from close collaboration with scientific experts in the field. Effectiveness is
      increased through the distribution of sound educational messages, through an
      array of commercial options that include books, magazines, videos, television and
      diet and exercise clubs.

PMID- 9778099
TI  - OK-432 develops CTL and LAK activity in mononuclear cells from regional lymph
      nodes of lung cancer patients.
AB  - We examined the effect of OK-432 on induction of cytotoxic T lymphocytes (CTL)
      directed against autologous tumor cells (ATC) and lymphokine-activated killer
      (LAK) cells from mononuclear cells separated from regional lymph node cells
      (RLMNCs) of 49 lung cancer patients. We also examined the phenotypic changes of
      RLMNCs during incubation with or without OK-432. Significant CTL activity and LAK
      activity against ATC developed from RLMNCs after stimulation with OK-432 or IL-2.
      Sequential treatment with OK-432 plus IL-2 or IL-2 plus OK-432 also developed
      significant CTL activity and LAK activity from RLMNCs. The CTL activity produced
      by OK-432 alone was as high as the CTL activity developed by IL-2 alone, OK-432
      plus IL-2, or IL-2 plus OK-432. There was no significant difference in the CTL
      activities achieved by these four treatments. The proportion of CD25+ cells in
      RLMNCs after incubation with OK-432 was twice that before incubation. Although OK
      432 increased IL-2 receptor expression on RLMNCs, it showed no synergistic effect
      with IL-2 in developing CTL and LAK activity. After incubation with OK-432, the
      proportion of HLA-DR + cells was also increased significantly. Moreover, the
      proportions of HLA-ABC+ and HLA-DR+ (class I and class II major
      histocompatibility complex antigens) cells in ATC were significantly larger than
      in Daudi cells. OK-432 alone could develop CTL activity against ATC from the
      RLMNCs of lung cancer patients that was as high as that developed by IL-2 alone
      or by sequential treatment with OK-432 plus IL-2 or IL-2 plus OK-432. The CTL
      developed from the RLMNCs of lung cancer patients may recognize class I and/or II
      antigens on the surface of ATC. These results indicated that treatment with OK
      432 might be therapeutically useful for lung cancer patients as a CTL inducer
      rather than a LAK inducer.

PMID- 9778100
TI  - Inhibition of type II collagen-induced arthritis in rats by triptolide.
AB  - The effects of purified triptolide, a diterpenoid triepoxide compound derived
      from the Chinese traditional anti-rheumatic medicinal plant extract, Tripterygium
      wilfordii Hook f (TWHf), were determined in type II collagen-induced arthritis
      (CIA) in rats. Lewis rats were immunized with bovine type II collagen and treated
      with purified triptolide 0.1 mg/kg/day or control (vehicle for triptolide) by
      daily gavage feedings for 28 days. Triptolide was well-tolerated with no evidence
      of toxicity. Treatment with triptolide resulted in significant delay in time to
      onset of arthritis (P = 0.039), as well as significantly decreased arthritis
      incidence (P = 0.024), clinical arthritis severity score (P < 0.0001),
      histopathological arthritis severity score (P < 0.0001), and in vivo cell
      mediated immunity to collagen (P = 0.0004). Triptolide appeared to be a potent
      immunomodulatory inhibitor of CIA in rats and this may account for the previously
      observed anti-rheumatic properties of crude extracts of TWHf, although more
      extensive studies will be needed to confirm these effects.

PMID- 9778101
TI  - Effect of macrophage colony-stimulating factor on mouse NK 1.1+ cell activity in
      vivo.
AB  - The effect of recombinant human macrophage colony-stimulating factor (rhM-CSF) on
      NK 1.1+ cell activity in vivo and in vitro was studied. An intravenous injection
      of rhM-CSF increased the numbers of NK 1.1+ cells in mouse spleen and blood and
      augmented the clearance of Yac-1 cells in vivo. Using a magnetic cell sorter
      (MACS), we purified NK 1.1+ cells from vehicle-injected and rhM-CSF-injected
      mouse spleen cells. More than 95% of the collected cells were NK 1.1 antigen
      positive. NK 1.1+ cells purified from rhM-CSF-injected mouse spleen cells
      exhibited (a) higher cytotoxic activity against Yac-1 cells, (b) higher
      proliferative responsiveness to interleukin (IL)-2 and (c) a greater production
      of interferon (IFN)-gamma in response to IL-2 and IL-12 compared to cells
      purified from vehicle-injected mouse spleen cells in vitro. These results suggest
      that the administration of rhM-CSF increases NK 1.1+ cell numbers and activates
      the cells in vivo.

PMID- 9778102
TI  - Delta9-tetrahydrocannabinol suppresses macrophage costimulation by decreasing
      heat-stable antigen expression.
AB  - Delta9-tetrahydrocannabinol (THC) suppresses several immunologic functions of
      macrophages. The costimulatory activity of a THC-exposed macrophage hybridoma was
      investigated by its ability to elicit interleukin-2 secretion by a helper T cell
      hybridoma activated with immobilized monoclonal anti-CD3 antibody. THC added at
      culture initiation inhibited the T cell response in a dose-dependent manner. When
      the macrophages were fixed with paraformaldehyde before culture, THC had no
      effect on T cell stimulation. However, macrophages, which were preincubated with
      THC and then fixed, were impaired in delivering costimulatory signals to T cells
      cultured without THC. The drug's inhibitory effect on macrophage costimulatory
      activity was reversible. THC exposure also decreased macrophage expression of
      heat-stable antigen (HSA). Antibody blocking experiments showed that HSA
      expressed on the macrophages provided an important costimulatory signal, whereas
      B7-1 and B7-2 molecules had a minor role. Treatment of the macrophages with
      phosphatidylinositol-specific phospholipase C cleaved HSA, but not the
      transmembrane B7 molecules, from the cell surface. Similar to THC, enzyme
      treatment significantly diminished macrophage costimulatory activity, which was
      also reversible. After drug or enzyme removal, HSA expression returned to the
      control level by 4 h. Therefore, THC suppresses macrophage costimulatory activity
      by diminishing cell surface expression of HSA.

PMID- 9778103
TI  - Effect of desipramine on immunological parameters in mice, and their reversal by
      stress.
AB  - Immunomodulation of cell-mediated immunity is demonstrated in mice, after
      administration of desipramine, a noradrenaline-reuptake inhibitor, with or
      without exposing the mice later to an acute swimming stress. A single i.p.
      injection of 10 mg/kg desipramine to naive mice increased the relative weight of
      their spleens, the response of their splenocytes to the mitogen concavaline-A and
      their ability to produce IL-10, as compared to saline controls. Exposing the
      desipramine-treated mice to a swimming stress significantly reduced these
      parameters, as well as the levels of IL-2 and IFN-gamma, as compared to
      desipramine-treated mice. Stress alone reduced the weight of the spleen, and the
      ability of splenocytes to produce IFN-gamma. As desipramine and acute stress have
      stimulatory effect on the sympathetic system, it is suggested that a concomitant
      administration of the drug and a stressful event of these mice, change the
      splenocytes' micro-environment of sympathetic transmitters, and inhibit their
      function. These results may be partially due to impairment in the T-helper cell
      function by a beta-adrenoreceptor-dependent mechanism.

PMID- 9778104
TI  - Mechanism for the development of pyothorax-associated lymphoma.
AB  - Malignant lymphomas frequently develop in the pleural cavity of patients with
      long-standing pyothorax. Thus, the term pyothorax-associated lymphoma (PAL) has
      been proposed for this type of tumor. Most PAL are of the type diffuse lymphoma
      of B cell and contain Epstein-Barr virus (EBV) DNA. This article reviews the
      mechanism for the development of PAL. The possible contribution of EBV infection,
      inflammatory cytokines and other genetic lesions, including the p53 gene, towards
      the growth advantage of neoplastic cells is described. Although the presence of
      EBV is focused in PAL cells, the contribution of EBV-mediated growth promotion in
      PAL is limited. Another important characteristic of PAL is that the virus antigen
      positive lymphoma develops in patients with pyothorax, in whom the systemic
      immunodeficiency is unlikely to be present. Therefore, in the course of the
      development of PAL, the mechanism for the evading host immune surveillance must
      be obvious. In this context, the production of an immunosuppressive cytokine from
      PAL cells, human histocompatibility leukocyte antigen class I alleles of patients
      with PAL, and the mutations of cytotoxic T lymphocyte epitopes in an EBV-latent
      antigen are described. These mechanisms could be involved in the development of
      PAL, an EBV-positive lymphoma developing in an immunocompetent host, and also
      shed light on the tumorigenesis of other EBV-positive neoplasms and on the
      lymphomagenesis of other inflammatory lesions.

PMID- 9778105
TI  - Polysialic acid, a unique glycan that is developmentally regulated by two
      polysialyltransferases, PST and STX, in the central nervous system: from
      biosynthesis to function.
AB  - Polysialic acid is a developmentally regulated carbohydrate composed of a linear
      homopolymer of alpha-2,8-linked sialic acid residues. This unique glycan is
      mainly attached to the neural cell adhesion molecule (N-CAM) and implicated in
      many morphogenic events of the neural cells by modulating the adhesive property
      of N-CAM. Recently, the cDNA that encodes polysialyltransferase, which is
      responsible for the polysialylation of N-CAM, was successfully cloned from three
      mammalian species. This review focuses on the molecular cloning of human
      polysialyltransferase, designated PST. It then describes the number of enzymes
      actually required for the polysialylation of N-CAM using an in vitro
      polysialyltransferase assay. Comparisons between PST and another
      polysialyltransferase, sialyltransferase X (STX), are made and it is demonstrated
      that both enzymes can independently form polysialic acid in vitro, but that
      during neural development they coordinately but distinctly synthesize polysialic
      acid on N-CAM. The role of polysialic acid in the central nervous system is also
      discussed. Finally, evidence that the two polysialyltransferases, PST and STX,
      apparently have distinct roles in the development of neural cells is provided by
      using a neurite outgrowth assay.

PMID- 9778106
TI  - Immunohistochemical characterization of two novel monoclonal antibodies that
      recognize human perivascular cells of the central nervous system and macrophage
      subsets.
AB  - Two monoclonal antibodies to cells of monocyte/macrophage lineage were
      established using a human glial cell-rich fraction as the immunogen. The
      antibodies, named GP-1 and GP-2, were originally found to react with perivascular
      cells of the central nervous system. They are immunohistochemically applicable on
      routinely formalin-fixed, paraffin-embedded tissue sections. GP-1 binds to a
      lysosomal protein, and GP-2 to a carbohydrate epitope of the cell membrane and
      lysosomes. Among the visceral organs, GP-1 labeled blood monocytes, almost all
      kinds of tissue and infiltrating macrophages in both normal and diseased states,
      and renal tubules. GP-1 staining of tissue macrophages tends to be intensified
      under inflammatory conditions. GP-1 staining also suggested that perivascular
      cells and macrophages had different ontogeny. GP-2 immunostained monocytes,
      Kupffer's cells, red pulp macrophages, infiltrating macrophages and reactive
      microglia, but not alveolar or tingible body macrophages. Besides those
      macrophages, GP-2 stained mantle zone lymphocytes, some hematopoietic cells,
      pneumocytes and renal collecting ducts. The staining pattern of ligands on THP-1
      and HL-60 neoplastic human macrophage cell lines was dissimilar to that of other
      macrophage markers, suggesting that they recognize unknown macrophage-related
      antigens.

PMID- 9778107
TI  - Alterations of p53 gene and Ha-ras gene are independent events in solar keratosis
      and squamous cell carcinoma.
AB  - In order to clarity the multiple-step progression from solar keratosis to
      squamous cell carcinoma, aberrations of the p53 gene (exons 2-11) and ras genes
      (exons 1 and 2) in solar keratosis and squamous cell carcinoma were investigated
      by polymerase chain reaction and single-strand conformation polymorphism
      analysis. In a series of Japanese patients, eight of 27 (30%) samples of solar
      keratosis and three of six (50%) samples of squamous cell carcinoma showed
      structural abnormalities in the p53 gene. Only one solar keratosis (4%) showed a
      point mutation in the Ha-ras gene but not in the p53 gene. Among these cases, no
      mutation of ras genes could be detected in squamous cell carcinoma. Simultaneous
      mutation of ras genes and the p53 gene was not detected in any cases of either
      solar keratosis or squamous cell carcinoma. It is concluded that aberrations of
      the p53 gene and ras genes are induced through independent processes of
      ultraviolet irradiation in the course of carcinogenic change from solar keratosis
      to squamous cell carcinoma.

PMID- 9778108
TI  - Expression of cytotoxic molecule TIA-1 in malignant lymphomas mimicking fulminant
      hepatitis.
AB  - Involvement of malignant lymphoma in the liver inducing fulminant hepatic failure
      has rarely been reported. Therefore, a close association between some lymphoma
      types with severe liver damage and the mechanism underlying the liver damage is
      intriguing. Three malignant lymphoma cases, which were clinically diagnosed as
      fulminant hepatitis, were collected from the autopsy records of Kawasaki Medical
      School (Kurashiki, Japan). All three cases were characterized by the presence of
      hepatosplenomegaly without superficial lymph node swelling, high elevation of
      transaminase and lactate dehydrogenase (LDH; especially LDH-2), and a quite
      aggressive clinical course. Immunohistochemically, the tumor cells in all three
      cases were positive for T cell intracellular antigen (TIA-1), which is a
      cytolytic protein in cytotoxic T and natural killer (NK) cells. The lymphomas
      were CD8+ peripheral T cell lymphoma (case 1), CD56+ T/NK cell lymphoma (case 2),
      and T cell lymphoma in a patient with mosquito hypersensitivity (case 3). Epstein
      Barr virus infection was demonstrated on the tumor cells of cases 2 and 3 using
      an in situ hybridization method and those cases showed high titers of serum
      interferon-gamma and Fas. Frequent apoptosis of liver cells, where the lymphoma
      cells had infiltrated, was revealed by a terminal deoxyribosyl transferase
      mediated deoxyuridine nick end-labeling (TUNEL) method. The findings in this
      study suggest that fulminant hepatic injury is closely associated with cytotoxic
      molecule TIA-1 expression of the lymphoma cells and that some specific mechanism
      may be involved in liver damage.

PMID- 9778109
TI  - Cutaneous allergic vasculitis: clinicopathological characterization and
      identification of apoptosis.
AB  - To elucidate the clinicopathological features of cutaneous allergic
      (leukocytoclastic) vasculitis (CAV), biopsied skin tissues of 32 patients with
      CAV were examined immunohistopathologically and compared with the main clinical
      features. Additionally, to obtain some clues to better understand the roles of
      infiltrating cells, particularly neutrophils in CAV, apoptosis and related
      antigens were investigated in vivo. The 32 patients with CAV were divided into
      two groups based on their clinical course: (i) non-recurrent (group I; nine
      cases); and (ii) recurrent (group II; 23 cases). Immunohistopathologically, group
      I was characterized by stereotypical necrotizing changes of CAV with fibrin
      exudation of small blood vessels in the upper cutis, and group II was
      characterized by CAV and fibrous thickening of the vascular walls with
      significant infiltration of CD3+, UCHL-1+ T cells. Group II was subdivided
      further: groups IIa (15 cases) and IIb (eight cases); that is, the former was
      notable for necrotizing changes of CAV, which tended to spread into the proper
      corium down to the lower cutis; whereas the latter exhibited considerably less
      marked histological changes of CAV without any spread to the lower cutis. In a
      comparison of the clinical data among the three groups, there were considerable
      differences in age, clinical course, localization of purpura and associated
      disease. In particular, group II showed a high frequency of connective tissue
      diseases. The presence of apoptosis was seen in a considerable number of
      neutrophils, and some nuclear debris turned out to be apoptotic bodies by the in
      situ terminal deoxytransferase (TdT)-catalyzed DNA nick end-labeling (TUNEL)
      method and electron microscopy. By combining immunohistochemistry with TUNEL, the
      majority of apoptotic neutrophils and nuclear debris was seen to be ingested by
      macrophages. In immunohistochemical examinations for apoptosis-related bcl-2
      protein and Fas antigen, bcl-2 was recognized only in the cytoplasm of
      infiltrating T cells, and Fas was positively stained on the cellular membranes of
      infiltrating T cells and neutrophils in a scattered fashion. Thus, a novel method
      for neutrophil disposal in CAV was suggested.

PMID- 9778110
TI  - The 5D4 antibody (anti-cyclin D1/D2) related antigen: cytoplasmic staining is
      correlated to the progression of gastric cancer.
AB  - In order to clarify the relationship between cyclin D1 and D2 (CD1/CD2)
      overexpression and progression, 191 gastric cancer cases (81 early and 110
      advanced cancers) were investigated using the 5D4 monoclonal antibody for both
      CD1/CD2 in immunohistochemistry. 5D4 immunoreactivity was noted in 68 (35.6%)
      cases, staining being restricted to the nucleus in 27 (14.1%) cases, the
      cytoplasm in 34 (17.8%) cases, and its presence in both the nucleus and cytoplasm
      in seven (3.7%). Cases demonstrating cytoplasmic positivity, including both
      positive cases, were significantly more frequent in advanced cancers (P = 0.010),
      those having lymph node metastasis (P = 0.004) and cases showing cancer invasion
      of vessels (P = 0.009), although no relation to histological malignant grading
      was apparent. In contrast, cases of nuclear positivity behaved no differently
      from 5D4-negative cases. Statistics showed a trend where survival in patients was
      worse in the cytoplasm-positive cases than the cytoplasm-negative group. However,
      multivariate analysis revealed no independent statistical significance in the
      cytoplasmic positivity of prognosis. Additional studies using DCS-6 antibody for
      CD1 and C-17 antibody for CD2, suggest that nuclear staining of 5D4 indicates the
      presence of CD1 but cytoplasmic staining is derived from an antigen that is
      related to CD2. In conclusion, the present results indicate that the accumulation
      of CD2 in the cytoplasm may play some role in the progression of gastric cancers
      but not prognosis; however, CD1 overexpression is not linked to either.

PMID- 9778111
TI  - Giant cell tumor of bone: a clinicopathologic study of prognostic factors.
AB  - Forty-seven cases of giant cell tumor of bone were clinicopathologically reviewed
      to determine any useful prognostic factors. Disease recurred in 11 cases. Eight
      of these cases had initially been treated with intracapsular piecemeal excision
      and three cases had been treated with wide excision. Nine of the 11 cases were
      classified as Grade III, two cases as Grade II, and one case as Grade II +
      fracture according to Campanacci's radiographic grading system. Intracapsularly
      excised cases had a high recurrence rate (47.1%). Metastasis to the lung occurred
      in three cases, each of which had been classified as Grade III. Although the
      radiographic Grade did not correlate with the rate of lung metastasis or
      recurrence, cases that metastasized to the lung or recurred tended to be
      radiographically aggressive. Disease recurred in eight of 24 Grade III cases; but
      in only two of 12 Grade II cases, in one of five Grade II + fracture cases, and
      none of six Grade I cases. p53 was expressed by mononuclear stromal cells in six
      cases. Disease recurred in four and lung metastasis occurred in three of these
      cases. p53 Expression correlated with rates of lung metastasis and recurrence. It
      was concluded that cases in which p53 is expressed have a high potential for lung
      metastasis and recurrence.

PMID- 9778112
TI  - Regulation of tumor growth as a 'total mass' in mice: apoptosis as a major
      mechanism in altering growth rates of single and multiple coexisting tumor
      nodules.
AB  - Earlier studies have suggested that a solid tumor behaves, in its general pattern
      of growth, like a normal integrated organ. In this study, the growth patterns of
      spherically shaped tumor nodules are re-examined using an accurate tumor volume
      measuring procedure, with the aim of investigating the possible role of apoptosis
      in regulating tumor growth. Observations revealed at least three distinct phases
      of growth: rapid growth phase I, slower growth phase II and 'stationary' phase
      III. Transition from one phase to the next was primarily due to an increase in
      the level of apoptosis and not to a decrease in the cell proliferation rate. The
      level of apoptosis, at a given phase, was similar in a single nodule and each of
      the multiple coexisting nodules of the same tumor line. However, temporal shifts
      in apoptosis levels caused early phase transition in coexisting nodules, such
      that their total volume was the same as that of a single nodule. It can be
      concluded that apoptosis appears to be a primary mechanism regulating tumor
      growth as a 'total mass', irrespective of whether the tumor exists in one or
      multiple nodules, if derived from the same tumor line.

PMID- 9778113
TI  - Chondromyxoid fibroma of the distal phalanx of the great toe: a tumor with
      unusual histological findings.
AB  - Chondromyxoid fibroma (CMF) rarely arises in the distal phalanx of the foot and
      less than 20 cases have been reported in the literature. It has also been known
      to show a wide spectrum of histology mimicking other primary bone tumors. An
      unusual case of CMF arising in the distal phalanx of the left great toe is
      reported because of its unique anatomic site of origin and histology. A 53-year
      old female presented with a slow growing, painful great toe of the left foot
      which she had had for 3 years. She had first noticed the mass 25 years ago. On
      admission, plain X-ray revealed an osteolytic mass with a sclerotic margin
      expanding to the distal phalanx of the great toe. Interestingly, the lesion was
      microscopically composed of hypercellular chondromyxoid lobules separated by
      hypocellular fibrous tissue, which is in contrast to the typical histology of
      CMF. In addition, the lesion showed an aggregate of tumor cells with pleomorphic
      multinucleate or giant nuclei within the chondromyxoid matrix, which were not
      similar to the osteoclast-like type. Perhaps these unusual histological findings
      may be associated with its long duration and presenting location.

PMID- 9778114
TI  - Small cell (oat cell) carcinoma of the breast.
AB  - A case of small cell (oat cell) carcinoma, which represents both the most
      distinctive and the least common type of breast carcinoma with neuroendocrine
      differentiation and usually shows the most aggressive behavior, is described.
      Radical mastectomy was performed on a 56-year-old female for a 10 cm tumor
      located in the outer part of the right breast with cutaneous ulceration
      Microscopically, the tumor predominantly consisted of a diffuse proliferation of
      small, round to ovoid cells with hyperchromatic nuclei and ill-defined, scant
      cytoplasm that was reminiscent of oat cell carcinoma of the lung. There were foci
      of invasive ductal carcinoma and ductal carcinoma in situ. Small cell carcinoma
      areas constituted approximately 90% of the neoplasm. The patient had axillary
      lymph node metastasis. The small tumor cells were argyrophilic and positive for
      CAM5.2, carcinoembryonic antigen, neuron-specific enolase, Leu-7, chromogranin A
      and synaptophysin. Flow cytometric analysis showed an aneuploid DNA content. The
      patient was alive and well without disease 4 years after surgery. Small cell
      carcinomas of the breast may exhibit a spectrum of malignancy that is comparable
      to similar tumors at better known primary sites.

PMID- 9778115
TI  - Mediastinal mature teratoma with coexistence of angiosarcoma, granulocytic
      sarcoma and a hematopoietic region in the tumor: a rare case of association
      between hematological malignancy and mediastinal germ cell tumor.
AB  - An association between mediastinal germ cell tumors (MGCT) and hematological
      malignancies (e.g. acute leukemia, malignant histiocytosis) has been recognized
      since 1984. A rare case of mediastinal mature teratoma with angiosarcoma, a
      hematopoietic region and granulocytic sarcoma is reported in a 29-year-old male.
      The resected tumor was 9.0 x 6.5 cm, weighed 65 g and showed extensive necrosis,
      forming a cyst. The histological features of the tumor showed a mature teratoma,
      which contained a large gland lined by ciliated epithelium, hyalinous cartilage,
      a paraganglion-like structure, well-differentiated angiosarcoma with atypical
      hematopoiesis composed of CD34-positive cells, and malignant round cells. The
      malignant round cells did not stain for CD34 but were positive for leukocyte
      common antigen (LCA) and c-kit product. From these findings, the round cells were
      diagnosed as granulocytic sarcoma. The patient died of metastasis of the
      granulocytic sarcoma in the tonsils and cervical lymph nodes 8 months after
      surgery. A leukemic condition was not present throughout the clinical course. The
      association between MGCT and hematological malignancy is a distinctive syndrome.
      However, its pathogenesis is still obscure and the origin of the hematopoietic
      malignancy has not been fully elucidated. In this particular case, it is
      suggested that the granulocytic sarcoma might have arisen from the abnormal
      hematopoietic area in the mediastinal teratoma.

PMID- 9778116
TI  - Oxyphilic cell variant of endometrioid adenocarcinoma.
AB  - A case of oxyphilic cell variant of endometrioid adenocarcinoma is presented. To
      the best of our knowledge, there have been only three such cases reported in the
      English literature. The patient was a 35-year-old Japanese female (gravida 0,
      para 0). She was slightly obese with profuse vaginal bleeding. Histological
      examination of the resected uterus revealed endometrioid adenocarcinoma with an
      exclusive oxyphilic cell component. There was no evidence of myometrial invasion
      nor lymph node metastases. Reported cases of oxyphilic cell variant of
      endometrioid adenocarcinoma, including the present case, were stages 0-1 and
      grades 1-2. Although further study is necessary to evaluate this variant,
      oxyphilic cell variant seems to be an early stage of adenocarcinoma and should be
      differentiated from eosinophilic metaplasia and other types of adenocarcinoma of
      the endometrium.

PMID- 9778117
TI  - Matrix metalloproteinases-2 and -9, and tissue inhibitor of metalloproteinases-1
      of the sheep placenta during the last third of gestation.
AB  - Uteroplacental and fetoplacental blood flows increase dramatically during the
      last third of gestation. Therefore, angiogenesis and tissue remodelling may
      regulate placental growth. On days 110, 120, 130, and 142 (term= 145+/-3; n=5
      ewes/day) of gestation, sheep placentae were separated into maternal (caruncular
      and intercaruncular) and fetal (cotyledonary and intercotyledonary) components;
      tissues were minced and cultured (24 h) and media were analysed for gelatinase
      activity and for tissue inhibitor of metalloproteinases-1 (TIMP-1) protein. Both
      the 72-kDa (matrix metalloproteinase-2; MMP-2) and 95-kDa (matrix
      metalloproteinase-9; MMP-9) gelatinases were detected by zymography. There was
      more (P<0.001) MMP-2 activity in the caruncle versus intercaruncle and
      intercotyledon, and all had greater MMP-2 activity (P<0.001) than the cotyledon.
      There was less (P<0.04) MMP-9 in the intercotyledon than in the other components.
      By Western analysis, there was more (P<0.004) TIMP-1 (30 kDa) in the caruncle
      conditioned media compared to the other tissues, which did not differ from each
      other (P> or =0.38). The immunohistochemical staining for MMP-2, MMP-9, and TIMP
      1 determined that staining was associated with the epithelial cells of the
      intercotyledon, the uterine glands, cells of the fetomaternal interface of the
      placentome (trophoblast and binucleate cells), and the endothelial cells of
      microvessels. Therefore, MMP-2, MMP-9, and TIMP-1 are present in the last third
      of gestation, suggesting that there is an ongoing tight regulation of tissue
      remodelling and growth throughout this critical time of pregnancy.

PMID- 9778119
TI  - Role of placenta growth factor (PIGF) in human extravillous trophoblast
      proliferation, migration and invasiveness.
AB  - Placenta growth factor (PlGF) is a homodimeric glycoprotein, 46-50 kDa in size,
      belonging to the vascular endothelial growth factor (VEGF) sub-family. It exists
      as two isoforms, PlGF-1 and -2, the latter having a heparin-binding domain. Like
      VEGF, it is a potent angiogenic factor; however, PlGF homodimers interact with
      the VEGF receptor Flt-1 (fms-like tyrosine kinase), but not with the kinase
      domain-containing region (KDR). Since PlGF is made by the human placenta and
      extravillous trophoblast (EV-T) cells of the human placenta express Flt-1 in
      situ, these cells may be responsive to PlGF. Therefore, this study examined
      whether first trimester EVT cells propagated in vitro expressed the mRNA or the
      protein of Flt-1 and PlGF, and whether exogenous PlGF-1 had any effect on EVT
      cell proliferation, migration or invasiveness. Immunocytochemical and RT-PCR
      analyses revealed that both normal and SV40 Tag-immortalized EVT cells expressed
      the protein and mRNA for Flt-1, but not for PlGF-1 or -2. Exogenous PlGF-1
      stimulated proliferation (measured by 3H-thymidine uptake) of normal EVT cells in
      a concentration-dependent manner, but only in the presence of excess heparan
      sulphate proteoglycans (HSPGs). These results raise two possibilities: that
      exogenous PlGF-1 (in spite of having a low affinity for heparin) was sequestered
      away from its receptor because of binding to heparan sulphate proteoglycans on
      the EVT cell surface or the ECM, or that HSPGs could modify the interaction
      between Flt-1 and PlGF. PlGF-1, in the presence or absence of HSPGs, however, had
      no effect on EVT migration or invasiveness, when measured with a transwell
      invasion (in the presence of Matrigel) or migration (in the absence of Matrigel)
      assay. These findings place PlGF amongst a large group of growth factors that
      promote EVT cell proliferation without influencing their migratory or invasive
      behaviours, and suggest that PlGF-Flt-1 interactions may be regulated by HSPGs in
      situ.

PMID- 9778120
TI  - Downregulation of protein kinase C by phorbol ester increases expression of
      epidermal growth factor receptors in transformed trophoblasts and amplifies human
      chorionic gonadotropin production.
AB  - Epidermal growth factor (EGF) and its homologue, transforming growth factor-alpha
      (TGF-alpha), regulate human chorionic gonadotropin (hCG) synthesis in the human
      placenta. The current study was designed to investigate the involvement of the
      protein kinase C pathway in EGF-mediated hCG-beta production by JAr
      choriocarcinoma cells. Downregulation of protein kinase C activity by chronic
      exposure to the phorbol ester, phorbol 12,13-dibutyrate (PDB), produced a greater
      increase in hCG-beta secretion than did activation of protein kinase C activity
      by short-term exposure to PDB. Pretreatment with the protein kinase C inhibitors
      calphostin and chelerythrine also resulted in enhanced basal and EGF-stimulated
      hCG-beta production. Individual concentrations (5 nM EGF and 500 nM PDB) that
      maximally stimulated hCG production, were additive in combination. The additive
      effect of PDB on EGF-induced hCG-beta secretion was mediated in part by increased
      JAr cell EGF-receptor concentrations detected by Western blot and Scatchard
      analyses. The results suggest that EGF and PDB stimulate hCG production in JAr
      cells by different but interactive mechanisms. It is speculated that
      downregulation of protein kinase C stimulates basal and EGF-mediated hCG-beta
      production by uninhibiting other signalling pathways that regulate hCG-beta
      secretion in trophoblasts.

PMID- 9778118
TI  - Effects of decidua-conditioned medium and insulin-like growth factor binding
      protein-1 on trophoblastic matrix metalloproteinases and their inhibitors.
AB  - The regulatory role of in vitro decidualized stromal cells (DESCM) and their main
      secretory product insulin-like growth factor binding protein-1 (IGFBP-1) was
      studied on the secretion of trophoblastic gelatinases and tissue inhibitor of
      metalloproteinase (TIMP-1). First trimester cytotrophoblastic cells (CTB) were
      obtained from abortions and cultured in vitro in presence or absence of DESCM or
      IGFBP-1. Secreted gelatinases were analysed in the culture supernatants by
      zymography and by measurements of the total gelatinolytic activity. TIMP-1, hCG,
      and fetal fibronectin (fFN) were measured by commercially available immunoassays.
      DESCM inhibited the total gelatinolytic activity of CTB but increased
      trophoblastic MMP-9, TIMP-1 and fFN. In contrast, IGFBP-1 increased the total
      gelatinolytic activity and TIMP-1, had no effect on MMP-2 , MMP-9 or fFN but
      inhibited hCG. It is concluded that a factor secreted by decidual cells inhibits
      the gelatinolytic property of trophoblast by increasing TIMP-1. Other decidual
      factors, as yet unidentified, increase MMP-2 and MMP-9 to an extent which does
      override the inhibitory effect of TIMP-1. Since in contrast to DESCM, IGFBP-1
      increases the total gelatinolytic activity of CTB, it cannot be the primary
      active decidual factor regulating the proteolytic activity of CTB. The
      possibility of an integrin-mediated effect of IGFBP-1 on CTB is discussed.

PMID- 9778121
TI  - Differential display analysis of oxygen-mediated changes in gene expression in
      first trimester human trophoblast cells.
AB  - Physiologic or pathologically induced periods of exposure to relatively low
      levels of oxygen during pregnancy affect the expression and function of certain
      genes in the placenta. In this study, the differential display technique was
      utilized to identify genes that are regulated in cultured cytotrophoblast cells
      by exposure to low levels of oxygen. Using this approach, four genes, which have
      been designated HRF-1, HRF-2, HRF-6, and HRF-8, were cloned and partially
      characterized. Northern blot analysis showed that clones HRF-1 and HRF-2 were
      downregulated in response to exposure to low levels of oxygen, whereas expression
      of HRF-6 and HRF-8 was increased. DNA sequencing and sequence analysis revealed
      that HRF-1 may represent an alternatively spliced or tissue-specific form of the
      Kruppel family zinc finger protein znfp104 gene. Clone HRF-2 showed a high degree
      of identity with exons 9, 10 and 11 of N33, a gene that is located within a
      homozygously deleted region of metastatic prostate cancer. Clones HRF-6 and HRF-8
      did not exhibit significant sequence identity with known sequences in GenBank and
      may represent novel genes. None of these genes have previously been shown to be
      present in trophoblast cells, nor have their expressions been shown to be
      regulated by oxygen. This study demonstrates that the differential display
      technique is a novel and effective method to analyse oxygen-mediated changes in
      gene expression in trophoblast cells.

PMID- 9778122
TI  - Immunohistochemical identification of epithelial and mesenchymal cell types in
      the chorioallantoic and yolk sac placentae of the guinea-pig.
AB  - To define the epithelial and mesenchymal cell types of the guinea-pig placenta,
      immunostaining patterns were determined for the intermediate filament proteins
      cytokeratin and vimentin. Chorionic and yolk sac placentae were studied at 15,
      20, 25, 29-30, 44-45, 55 and 65 days of gestation. Immunohistochemistry was
      performed on 5-microm thick sections of paraffin embedded tissue using specific
      antibodies against cytokeratin, a marker for epithelial cells, including
      trophoblast, and vimentin, a marker for mesenchymal cells and stromal decidua.
      Immunostaining was identified by the avidin-biotin-peroxidase technique with
      diaminobenzidine as the chromogen. Most of the surface of the placenta is covered
      by the columnar epithelium of the parietal yolk sac, beneath which is found a
      layer of chorionic giant cells. In the guinea-pig, a sheet of mesenchymal cells
      interposed between these cell layers immunostained for vimentin, a protein that
      is expressed only intracellularly, and had nuclei orientated parallel to the
      surface of the placenta. This cell layer is quite different from Reichert's
      membrane in the rat or mouse, which is acellular. Within the main placenta,
      cytokeratin immunostaining demonstrated that the trophoblasts lining the large
      maternal blood sinuses are different in character from the surrounding
      syncytiotrophoblast, confirming earlier ultrastructural observations. In the
      subplacenta, some trophoblast did not immunostain for cytokeratin and there was
      non-specific staining of cellular debris, so that immunostaining for vimentin
      provided the clearest indication of the maternal-fetal interface. In later stages
      of gestation (30-55 days), trophoblasts invading the walls of maternal arteries
      immunostained for cytokeratin and were vimentin negative. In early gestation,
      however, trophoblast invasion of the maternal vessels was indicated by cells that
      were immunoreactive for both cytokeratin and vimentin.

PMID- 9778123
TI  - Immunohistochemical identification of the receptor for urokinase plasminogen
      activator associated with fibrin deposition in normal and ectopic human placenta.
AB  - The receptor for urokinase plasminogen activator (uPAR) is a key molecule in cell
      surface-directed plasminogen activation. uPAR binds urokinase plasminogen
      activator (uPA) and thereby focuses plasminogen activation on the cell surface.
      Plasmin dissolves fibrin deposits and facilitates cell migration during tissue
      repair processes by degrading the extracellular matrix. During human implantation
      and placental development, plasmin is considered important for both trophoblast
      migration/invasion and for fibrin surveillance. This study examined the
      expression of uPAR in normal and ectopic human placentae by immunohistochemistry.
      In first and third trimester normal placentae as well as in tubal ectopic
      placental tissues, a high uPAR expression was seen in the trophoblast associated
      with deposits of fibrin-type fibrinoid. Extravillous trophoblast of the basal
      plate, of the cell islands, and of the cell columns was also positive for uPAR in
      the first trimester whereas at term the expression of the protein was decreased.
      Moreover, uPAR immunostaining was observed in decidual cells throughout normal
      gestation and in endometrial tissues of patients with ectopic pregnancies. These
      findings suggest that uPAR participates in placental development and in
      trophoblast invasion particularly in the first trimester of pregnancy and that
      uPAR is involved in repair mechanisms of the trophoblast and fibrin surveillance.

PMID- 9778125
TI  - Glycaemic regulation of glucose transporter expression and activity in the human
      placenta.
AB  - To determine whether the expression and activity of glucose transporters in human
      trophoblast are regulated by glucose, syncytiotrophoblast cells, choriocarcinoma
      cells, and villous fragments were incubated with a range of glucose
      concentrations (0-20 mM, 24 h). Expression of GLUT1 and GLUT3 glucose
      transporters was measured by immunoblotting, while glucose transporter activity
      was determined by [3H]2-deoxyglucose uptake in the cultured cells. GLUT1
      expression in syncytial cells was enhanced following incubation in absence of
      glucose, reduced by incubation in 20 mM glucose but was not altered by incubation
      at 1 or 12 mM glucose. Transporter activity was inversely related to
      extracellular glucose over the entire range of concentrations tested (0-20 mM).
      Incubation of villous fragments in 20 mM glucose produced a limited suppression
      of GLUT1 expression, but no effects were noted following incubation at 0 or 1 mM
      glucose. Neither GLUT1 expression in JAr and JEG-3 choriocarcinoma cells nor
      transport activity in JEG-3 cells was affected by extracellular glucose
      concentration. Unlike syncytial cells, JAr, JEG-3 and BeWo all expressed GLUT3
      protein in addition to GLUT1. These results show that while syncytiotrophoblast
      GLUT1 expression is altered at the extremes of extracellular glucose
      concentration, it is refractory to glucose alone at lower concentrations. By
      contrast, an inverse relationship exists between glucose transporter activity and
      extracellular glucose. This suggests that there are post-translational regulatory
      mechanisms which may respond to changes in extracellular glucose concentration.

PMID- 9778124
TI  - Heme oxygenase and nitric oxide synthase in the placenta of the guinea-pig during
      gestation.
AB  - Nitric oxide (NO) and carbon monoxide (CO) are novel gaseous chemical messengers
      that play key roles in cell function and cell-cell communication in many organ
      systems, including the cardiovascular system. Although the presence of NO
      synthase (NOS) in the placenta and its role in the regulation of fetoplacental
      and uteroplacental blood flow are well established, little is known about
      placental expression and activity of heme oxygenase (HO), the enzyme that
      catalyses the oxidation of heme to CO, biliverdin and iron, during gestation. The
      objectives of this study were to elucidate the localization of HO-1 and HO-2
      isoforms relative to NOS III protein, and to determine the enzymatic activity of
      HO in the placenta of the guinea-pig during gestation. Placentae were obtained
      from pregnant guinea-pigs at gestational day (GD) 34, 50, 62 and full term (term,
      about GD 68). Immunohistochemical localization of HO-1, HO-2 and NOS III protein
      was conducted using selective polyclonal antibodies. HO activity was determined
      by using a gas chromatographic method to measure the rate of formation of CO from
      heme. Faint staining for HO-1 was observed in the adventitial layer of larger
      fetal blood vessels of the placenta at GD 34. The intensity of this staining was
      higher at GD 50 and GD 62, and decreased at full term. Similar areas in serial
      sections of placentae obtained at these selected times during gestation exhibited
      lower staining intensity when incubated with anti-HO-2 antiserum. Placental HO
      activity was significantly increased (P<0.05) at GD 62 compared with GD 34, GD 50
      and full term. NOS III (endothelial constitutive NOS) staining was highest at GD
      34, decreasing thereafter, and was localized mostly to trophoblast lining
      maternal channels. The data demonstrate that, in the guinea-pig, placental HO and
      NOS differ in tissue localization during the second half of gestation, with
      expression of HO protein and its catalytic activity being higher during near-term
      pregnancy. In a preliminary immunohistochemical investigation of the full-term
      human placenta, HO-1 protein was localized primarily in the adventitial region of
      fetal blood vessels of stem chorionic villi. In view of the vasodilator action of
      CO and NO, the HO and NOS systems may play key roles in the regulation of
      placental haemodynamics.

PMID- 9778126
TI  - Non-transferrin iron uptake by trophoblast cells in culture. Significance of a
      NADH-dependent ferrireductase.
AB  - This study shows that trophoblast cells in culture are able to take up 59Fe from
      both Fe(III)nitrilotriacetate (NTA) and Fe-ascorbate. Fe in the presence of
      ascorbate is assumed to be Fe(III) in equilibrium with Fe(II). Kinetic parameters
      for non-transferrin iron uptake are determined from initial rate experiments,
      yielding Vmax=366 pmol/mg protein/5 min and Km=0.96 microM for Fe(III)NTA and
      Vmax=4043 pmol/mg protein/5 min and Km= 1.3 microM for Fe-ascorbate. Since
      trophoblast cells in culture reduce extracellular Fe(III)CN, and uptake of 59Fe
      from Fe-ascorbate is higher than that from Fe(III)NTA, it is suggested that
      reduction of Fe(III) precedes uptake. Uptake of 59Fe from both Fe-ascorbate and
      Fe(III)NTA is inhibited by Fe(II)chelator ferrozine and membrane-impermeable
      Fe(III)CN, further supporting this hypothesis. Studies with microvillous membrane
      vesicles (MMV) and basal membrane vesicles (BMV) reveal the presence of a NADH
      dependent ferrireductase. Reduction of Fe(III)CN follows Michaelis-Menten
      kinetics, both with respect to [NADH] and [Fe]. NADPH is ineffective as electron
      donor. The rate of Fe(III)CN reduction by BMV is 2.5 times higher compared to
      MMV, while Km values for Fe(III)CN and NADH are not significantly different.
      These results reveal that a transmembrane NADH-dependent ferrireductase plays a
      role in uptake of non-transferrin iron. The possibility that this enzyme system
      is involved in iron transfer across the basal membrane is discussed.

PMID- 9778127
TI  - Uptake and transport by the ovine placenta of neutral nonmetabolizable amino
      acids with different transport system affinities.
AB  - Placental uptake and transport of three nonmetabolizable amino acids with
      different reactivities for transport systems were studied in sheep under normal
      physiologic conditions. Methylaminoisobutyric acid (MeAIB), which has specific
      affinity for the sodium-dependent A system transporters, demonstrated placental
      concentrative uptake from the uterine and the umbilical circulations, but
      virtually no transport from mother to fetus. By contrast, aminoisobutyric acid
      (AIB) and aminocyclopentane-1-carboxylic acid (ACP), which have affinity for both
      sodium-dependent and sodium-independent transporters, demonstrated both
      concentrative uptake and transport from mother to fetus. ACP transport rate to
      the fetus was approximately twice the AIB transport rate. It is concluded that a
      neutral amino acid which interacts almost exclusively with the weakly reversible
      system A transporters may be transported rapidly into the placenta and may attain
      high concentrations within this organ but cannot escape from placenta to fetus
      down its own concentration gradient because the exit route is controlled by
      reversible amino acid transporters at the fetal surface of the placenta.
      Conversely, high affinity for reversible Na-independent transporters may be a
      necessary condition for the rapid transport of an amino acid from placenta to
      fetus.

PMID- 9778128
TI  - The investigation of placental relaxation and estimation of placental perfusion
      using echo-planar magnetic resonance imaging.
AB  - Echo-planar imaging (EPI) is a form of magnetic resonance imaging (MRI) which
      acquires images in milliseconds rather than minutes as with conventional MRI. The
      images produced using EPI are affected by the physiological environment in which
      the hydrogen atoms producing the signals are found, a process referred to as
      relaxation. Also by producing images a matter of milliseconds apart,
      quantification of perfusion within the tissue being imaged is feasible. The
      objective of this study was to investigate T1 and T2 relaxation times along with
      perfusion in placentae from normal pregnancies at different gestations and also
      to compare these to pregnancies complicated by abnormal placental function. A
      cross-sectional study of normal and compromised pregnancies from 20 weeks to term
      and a longitudinal study of normal pregnancy were performed. Placental T1, T2
      relaxation times, and perfusion were measured using echo-planar magnetic
      resonance imaging. Placental T1 and T2 relaxation times decreased in normal
      pregnancy (P<0.001). Relaxation times in pregnancies associated with placental
      pathology appeared to be reduced for that gestation although the numbers were too
      small to allow any statistical validation. No differences in placental perfusion
      with gestation or between normal and compromised pregnancy were demonstrated
      using this technique. This is the first demonstration of placental magnetic
      resonance relaxation and perfusion measurements in normal pregnancy using echo
      planar magnetic resonance imaging. In the future it may be possible to identify
      compromised pregnancies by differences in placental T1 and T2 relaxation times,
      using this novel non-invasive technique.

PMID- 9778129
TI  - Detection of Toxoplasma gondii in 94 placentae from infected women by polymerase
      chain reaction, in vivo, and in vitro cultures.
AB  - The biological diagnosis of congenital toxoplasmosis at birth is important to
      determine the infant's treatment. The aim of this study was to evaluate the
      placenta results in the congenital toxoplasmosis diagnosis and to compare them
      with those obtained with other samples collected at birth (cord blood and newborn
      blood). A total of 94 placentas, of which 33 came from fetuses suspected of or
      with proven congenital toxoplasmosis (CT+) and 61 from definitely or probably non
      infected fetuses (CT-), was analysed by in vitro culture, mouse inoculation and
      polymerase chain reaction (PCR). The PCR sensitivity was higher (60.9 per cent)
      than that of cell culture (29.6 per cent) and mouse inoculation (51.5 per cent)
      but the number of PCR positive results in CT - patients was also higher (9.5 per
      cent). The presence of Toxoplasma gondii in the placenta tissues was the only
      argument at birth (IgM and neosynthesized Ig were negative) in three out of the
      33 CT+ cases. The detection of IgM by ELISA and ISAGA and the detection of
      neosynthesized Ig by immunoblotting were more satisfactory to diagnose congenital
      toxoplasmosis but the placenta analysis was important to improve the sensitivity
      of the diagnosis at birth, especially when the prenatal diagnosis was negative or
      not performed.

PMID- 9778130
TI  - Regulation of term and preterm labour, Castellina, Italy, 28 October-1 November
      1997.

PMID- 9778131
TI  - Analysis of novel hydroperoxides and other metabolites of oleic, linoleic, and
      linolenic acids by liquid chromatography-mass spectrometry with ion trap MSn.
AB  - Linoleate is oxygenated by manganese-lipoxygenase (Mn-LO) to 11S
      hydroperoxylinoleic acid and 13R-hydroperoxyoctadeca-9Z,11E-dienoic acid, whereas
      linoleate diol synthase (LDS) converts linoleate sequentially to 8R
      hydroperoxylinoleate, through an 8-dioxygenase by insertion of molecular oxygen,
      and to 7S,8S-dihydroxylinoleate, through a hydroperoxide isomerase by
      intramolecular oxygen transfer. We have used liquid chromatography-mass
      spectrometry (LC-MS) with an ion trap mass spectrometer to study the MSn mass
      spectra of the main metabolites of oleic, linoleic, alpha-linolenic and gamma
      linolenic acids, which are formed by Mn-LO and by LDS. The enzymes were purified
      from the culture broth (Mn-LO) and mycelium (LDS) of the fungus Gaeumannomyces
      graminis. MS3 analysis of hydroperoxides and MS2 analysis of dihydroxy- and
      monohydroxy metabolites yielded many fragments with information on the position
      of oxygenated carbons. Mn-LO oxygenated C-11 and C-13 of 18:2n-6, 18:3n-3, and
      18:3n-6 in a ratio of approximately 1:1-3 at high substrate concentrations. 8
      Hydroxy-9(10)epoxystearate was identified as a novel metabolite of LDS and oleic
      acid by LC-MS and by gas chromatography-MS. We conclude that LC-MS with MSn is a
      convenient tool for detection and identification of hydroperoxy fatty acids and
      other metabolites of these enzymes.

PMID- 9778133
TI  - Lipase specificity toward some acetylenic and olefinic alcohols in the
      esterification of pentanoic and stearic acids.
AB  - The esterification of five medium- and long-chain acetylenic alcohols (2-nonyn-1
      ol, 10-undecyn-1-ol, 6-octadecyn-1-ol, 9-octadecyn-1-ol, and 13-docosyn-1-ol),
      seven olefinic alcohols (cis-3-nonen-1-ol, 10-undecen-1-ol, cis-6-octadecen-1-ol,
      cis-9-octadecen-1-ol, trans-9-octadecen-1-ol, trans-9, trans-11-octadecadien-1
      ol, cis-9,cis-12-octadecadien-1-ol), and four short-chain unsaturated alcohols
      (allyl alcohol, 3-butyn-1-ol, 3-pentyn-1-ol, and cis-2-penten-1-ol) with
      pentanoic or stearic acid in the presence of various lipase preparations was
      studied. With the exception of 2-nonyn-1-ol, where Lipase AY-30 (Candida rugosa)
      was used as the biocatalyst, the esterification of C11, C18, and C22 acetylenic
      alcohols with pentanoic acid appeared to be generally unaffected by the presence
      of an acetylenic bond in the alcohol as relatively high yields of the
      corresponding esters (78-97%) were obtained. However, medium- and long-chain
      olefinic alcohols were discriminated by Lipase AY-30, Lipolase 100T (Rhizomucor
      miehei), and especially by porcine pancreatic lipase (PPL), when esterification
      was conducted with pentanoic acid. Esterification of medium- and long-chain
      acetylenic or olefinic alcohols with a long-chain fatty acid, stearic acid, was
      very efficient except when Lipase AY-30 and Lipolase 100T were used. Short-chain
      unsaturated alcohols were much more readily discriminated. 3-Pentyn-1-ol and 3
      butyn-1-ol were difficult (<5% yield) to esterify with pentanoic or stearic acid
      in the presence of Lipase AY-30 and PPL, respectively. Very low yields (<26%) of
      esters were produced when 3-butyn-1-ol and 3-pentyn-1-ol were reacted with
      pentanoic or stearic acid, when catalyzed by lipase from Candida cylindracea. No
      reaction took place between 3-butyn-1-ol and stearic acids in the presence of
      Lipase AY-30. Esterification of short-chain acetylenic and olefinic alcohols was
      most efficiently achieved with Lipolase 100T (Rhizomucor miehei), Lipozyme IM20
      (Rh. miehei), or Novozyme 435 (Candida antarctica) as the biocatalyst.

PMID- 9778132
TI  - Characterization of phospholipase D activity in bovine photoreceptor membranes.
AB  - Phospholipase D (E.C. 3.1.4.4.) was detected in isolated bovine rod outer
      segments (ROS) and its properties determined. The enzyme activity was assayed
      using either a sonicated microdispersion of 1,2-diacyl-sn-[2(3)H]glycerol-3
      phosphocholine (PC), or [14C]ethanol. Using [3H]PC and ethanol as a substrate, we
      were able to detect the hydrolytic properties as well as the
      transphosphatidylation reaction catalyzed by phospholipase D (PLD): formation of
      [3H]phosphatidic acid and phosphatidylethanol [3H]PtdEt; whereas with
      [14C]ethanol or [3H]glycerol in the absence of exogenous PC, only
      transphosphatidylation reactions were detected (formation of [14C]PtdEt or
      [3H]phosphatidylglycerol, respectively). The use of varying concentrations of
      [3H]PC and 400 mM of ethanol gave an apparent Km value for PC of 0.51 mM and a
      Vmax value of 111 nmol x h(-1) x (mg protein)(-1). The activity was linear up to
      60 min of incubation and up to 0.2 mg of protein. The optimal ethanol
      concentration was determined to be 400 mM, with an apparent Km of 202 mM and a
      Vmax value for ethanol of 125 nmol x h(-1) x (mg protein)(-1). A clear pH optimum
      was observed around 7. PLD activity was increased in the presence of 3-[(3
      cholamidopropyl)dimethylammonio]-1-propane-sulfonate or sodium deoxycholate and
      inhibited with Triton X-100. The enzyme activity was also activated in the
      presence of Ca2+ or Mg2+ (1 mM) although these ions were not required for
      measuring PLD activity. The high specific activity of PLD found in purified ROS
      compared to the activity found in other subcellular fractions of the bovine
      retina suggests that this enzymatic activity is native to ROS. The present report
      is the first evidence of PLD activity associated with photoreceptor ROS.

PMID- 9778134
TI  - The triggering signal dictates the effect of docosahexaenoic acid on lymphocyte
      function in vitro.
AB  - Docosahexaenoic acid (DHA) is an n-3 fatty acid beneficial to several human
      conditions including inflammation and autoimmune disease. To better understand
      the effect of DHA on immunity, we monitored the rise in cytosolic free calcium,
      interleukin 2 receptor (IL2R) expression, and proliferation of splenic
      lymphocytes triggered with three different stimuli in the presence or absence of
      DHA. We found that 10 microg DHA/mL suppressed concanavalin A-induced mitogenesis
      and the mixed lymphocyte reaction while concurrently enhancing proliferation
      stimulated with anti-Thy-1 antibodies. Proliferation, as measured by
      [3H]thymidine incorporation after 2 to 5 d of culture, was affected by DHA, but
      earlier activation effects such as elevation of cytosolic free calcium and IL2R
      expression were not altered. These results imply that DHA incorporated into
      membrane phospholipids differentially affects the activity of distinct membrane
      bound receptors and signaling molecules. This result suggests that DHA may be
      used to modulate immune responses selectively, e.g., to suppress undesired
      autoimmunity while maintaining protective immunity.

PMID- 9778135
TI  - Replacement of partially hydrogenated soybean oil by palm oil in margarine
      without unfavorable effects on serum lipoproteins.
AB  - We have compared the effects of three different margarines, one based on palm oil
      (PALM-margarine), one based on partially hydrogenated soybean oil (TRANS
      margarine) and one with a high content of polyunsaturated fatty acids (PUFA
      margarine), on serum lipids in 27 young women. The main purpose of the study was
      to test if replacement of trans fatty acids in margarine by palmitic acid results
      in unfavorable effects on serum lipids. The sum of saturated fatty acids (12:0,
      14:0, 16:0) was 36.3% of total fatty acids in the PALM-diet, the same as the sum
      of saturated (12:0, 14:0, 16:0) (12.5%) and trans (23.1%) fatty acids in the
      TRANS-diet. This sum was 20.7% in the PUFA-diet. The content of oleic acid was
      37.9, 35.2, and 38.6%, respectively, in the three diets, whereas linoleic acid
      amounted to 16, 13.5, and 27.3%, respectively. Total fat provided 30-31% and the
      test margarines 26% of total energy in all three diets. The subjects consumed
      each of the diets for 17 d in a Latin-square crossover design. There were no
      significant differences in total cholesterol, low density lipoprotein (LDL)
      cholesterol and apolipoprotein B (apoB) between the TRANS- and the PALM-diets.
      High density lipoprotein (HDL)-cholesterol and apoA-1 were significantly higher
      on the PALM-diet compared to the TRANS-diet whereas the ratio of LDL-cholesterol
      to HDL-cholesterol was lower, although not significantly (P = 0.077) on the PALM
      diet. Total cholesterol, LDL-cholesterol, and apoB were significantly lower on
      the PUFA-diet compared to the two other diets. HDL-cholesterol was not different
      on the PALM- and the PUFA-diets but it was significantly lower on the TRANS-diet
      compared to the PUFA diet. Compared to the PUFA-diet the ratio of LDL- to HDL
      cholesterol was higher on both the PALM- and the TRANS-diets whereas apoA-1 was
      not different. Triglycerides and lipoprotein (a) were not significantly different
      among the three diets. We concluded that nutritionally, palmitic acid from palm
      oil may be a reasonable alternative to trans fatty acids from partially
      hydrogenated soybean oil in margarine if the aim is to avoid trans fatty acids. A
      palm oil-based margarine is, however, less favorable than one based on a more
      polyunsaturated vegetable oil.

PMID- 9778136
TI  - Different degrees of moderate iron deficiency modulate lipid metabolism of rats.
AB  - Severe iron deficiency affects lipid metabolism. To investigate whether moderate
      iron depletion also alters lipid variables-including lipid levels in serum and
      liver, hepatic lipogenesis, and fatty acid composition indicative of an impaired
      desaturation-we carried out experiments with rats fed 9, 13, and 18 mg iron/kg
      diet over a total of 5 wk. The study also included three pair-fed control groups
      and an ad libitum control group, fed with 50 mg iron/kg diet. The iron-depleted
      rats were classified as iron-deficient on the basis of reduced serum iron,
      hemoglobin concentration, and hematocrit. All moderately iron-deficient rats had
      significantly lower cholesterol concentrations in liver and serum lipoproteins
      than their pair-fed controls. Rats with the lowest dietary iron supply had higher
      concentrations of hepatic phosphatidylcholine (PC) and phosphatidylethanolamine
      (PE), lower activities of glucose-6-phosphate dehydrogenase, malic enzyme and
      fatty acid synthase, and higher triacylglycerol concentrations in serum
      lipoproteins than the corresponding pair-fed control rats. Moderate iron
      deficiency also depressed the serum phospholipid level. Moreover, several
      consistent significant differences in fatty acid composition of hepatic PC and PE
      occurred within moderate iron deficiency, which indicate impaired desaturation by
      delta-9 and delta-6 desaturases of saturated and essential fatty acids. We
      conclude that lipid variables, including cholesterol in liver and serum
      lipoproteins as well as fatty acid desaturation, reflect the gradations of iron
      status best and can be used as an indicator of the degree of moderate iron
      deficiency.

PMID- 9778137
TI  - Effects of long-term feeding of marine oils with different positional
      distribution of eicosapentaenoic and docosahexaenoic acids on lipid metabolism,
      eicosanoid production, and platelet aggregation in hypercholesterolemic rats.
AB  - Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were distributed
      mainly in the sn-1,3 positions of seal oil triglyceride and in the sn-2 position
      of squid oil triglyceride. Seal oil-rich or squid oil-rich fats having constant
      saturated/monounsaturated/polyunsaturated fatty acid (PUFA) and n-6/n-3 PUFA
      ratios were fed to exogenously hypercholesterolemic rats for 1 60 d. The control
      fat contained linoleic acid as the sole PUFA. Before starting the experimental
      diets, rats were orally treated with high doses of vitamin D for 4 d to
      accelerate atherogenesis. The percentage of arachidonic acid in
      phosphatidylcholine and phosphatidylethanolamine of liver, platelets, and aorta
      was lower in the marine oil groups than in the control group, seal oil being more
      effective than squid oil. Maximal platelet aggregation induced by collagen was
      significantly lower in both marine oil groups. Platelet thromboxane (TX) A2
      production induced by collagen or thrombin was markedly reduced by feeding seal
      or squid oils, the reduction being more pronounced in the seal oil than in the
      squid oil group. Aortic prostacyclin (PGI2) production was the same among the
      three groups. The ratio of the productions of aortic PGI2 and platelet TXA2 was
      significantly higher in the seal oil than in the control group. Although there
      was no difference in intimal thickness among the three groups, the aortic
      cholesterol content was significantly lower in the marine oil groups than in the
      control group. These results showed that the main effects in rats of the
      different intramolecular distributions of EPA and DHA in dietary fats were on
      arachidonic acid content in tissue phospholipids and on platelet TXA2 production.

PMID- 9778138
TI  - Effects of dietary methionine and cystine on lipid metabolism in hepatoma-bearing
      rats with hyperlipidemia.
AB  - Abnormal lipid metabolism and its restoration by dietary methionine (Met) and
      cystine (Cys) were studied in Donryu rats subcutaneously implanted with an
      ascites hepatoma cell line of AH109A. The hepatoma-bearing rats exhibited
      hyperlipidemia characterized by rises in serum triglyceride and cholesterol
      levels. Decreased lipoprotein lipase (LPL) activities in epididymal adipose
      tissue, cardiac muscle, and gastrocnemius as well as increased fatty acid
      mobilization from adipose tissue were considered to be responsible for the
      hepatoma-induced hypertriglyceridemia, while increased hepatic cholesterogenesis
      and decreased steroid excretion into feces were thought to be responsible for the
      hepatoma-induced hypercholesterolemia. Dietary-supplemented Met or Cys reduced
      the AH109A-induced hypertriglyceridemia with suppression of fatty acid synthesis
      in the host liver. Met restored the fall of LPL activities, while Cys did not.
      Dietary Met or Cys also reduced the hypercholesterolemia with restoration of
      decreased bile acid excretion into feces. These results suggest that dietary Met
      or Cys is hypolipidemic in the hepatoma-bearing rats with slight differences in
      their modes of action.

PMID- 9778140
TI  - Carnitine palmitoyltransferase I, carnitine palmitoyltransferase II, and acyl-CoA
      oxidase activities in Atlantic salmon (Salmo salar).
AB  - Salmon farmers are currently using high-energy feeds containing up to 35% fat;
      the fish's capability of fully utilizing these high-energy feeds has received
      little attention. Carnitine is an essential component in the process of
      mitochondrial fatty acid oxidation and, with the cooperation of two carnitine
      palmitoyltransferases (CPT-I and CPT-II) and a carnitine acylcarnitine
      transporter across the inner mitochondrial membrane, acts as a carrier for acyl
      groups into the mitochondrial matrix where beta-oxidation occurs. However, no
      reports are available differentiating between CPT-I and CPT-II activities in
      fish. In order to investigate the potential for fatty acid catabolism, the
      activities of key enzymes involved in fatty acid oxidation were determined in
      different tissues from farmed Atlantic salmon (Salmo salar), i.e., acyl-CoA
      oxidase (ACO) and CPT-I and CPT-II. Malonyl-CoA was a potent inhibitor of CPT-I
      activity not only in red muscle but also in liver, white muscle, and heart. By
      expressing the enzyme activities per wet tissue, the CPT-I activity of white
      muscle equaled that of the red muscle, both being >> liver. CPT-II dominated in
      red muscle whereas the liver and white muscle activities were comparable. ACO
      activity was high in the liver regardless of how the data were calculated. Based
      on the CPT-II activity and total palmitoyl-L-carnitine oxidation in white muscle,
      the white muscle might have a profound role in the overall fatty acid oxidation
      capacity in fish.

PMID- 9778139
TI  - Dietary proteins modulate the effects of fish oil on triglyceridemia in the rat.
AB  - Sprague-Dawley rats were fed purified diets varying in both protein (20%) and
      lipid (11%) content for 28 d to verify the independent and interactive effects of
      dietary proteins and lipids on serum and hepatic lipids, and on tissue
      lipoprotein lipase (LPL) activity in both fasted and postprandial states. These
      diets consisted of either casein-menhaden oil, casein-coconut oil, soy protein
      menhaden oil (SPMO), soy protein-coconut oil, cod protein-menhaden oil, or cod
      protein-coconut oil. A randomized 3 x 2 factorial design was used. A significant
      protein-lipid interaction was seen on serum triglyceride levels: menhaden oil,
      compared with coconut oil, induced a decrease in serum triglyceride levels when
      combined with soy protein but not when combined with cod protein and casein. The
      lower serum triglyceride concentrations observed in the SPMO-fed rats could be
      the result of decreased hepatic triglycerides when soy protein was compared with
      casein and when menhaden oil was compared with coconut oil. Total LPL activity in
      the heart was higher in menhaden oil-fed rats than in coconut oil-fed rats in the
      postprandial state. The higher LPL activity in the heart could, however, explain
      only 10% of the reduction of serum triglycerides, contributing slightly to the
      lowering effects of SPMO diet on serum triglycerides. Therefore, the present
      results indicate that dietary proteins can modulate the effects of fish oil on
      triglyceridemia in the rat, and that could be mainly related to specific
      alterations in hepatic lipid concentrations.

PMID- 9778142
TI  - An efficient ultrasound-assisted zinc reduction of fatty esters containing
      conjugated enynol and conjugated enynone systems.
AB  - Reduction of methyl 8-hydroxy-11-E/Z-octadecen-9-ynoate (1) with zinc in either
      aqueous n-propanol or water under concomitant ultrasound irradiation furnished a
      mixture of methyl 8-hydroxy-9Z,11E-octadecadienoate (3a) and methyl 8-hydroxy
      9Z,11Z-octadecadienoate (3b) (96% yield). Reduction of methyl 8-oxo-11-E/Z
      octadecen-9-ynoate (2) under similar conditions gave methyl 8-oxo-10-Z
      octadecenoate exclusively (4, 70%). The latter compound was epoxidized and
      converted to a C18 furanoid fatty ester (6, methyl 8,11-epoxy-8,10
      octadecadienoate) in 70% yield.

PMID- 9778141
TI  - Phospholipid composition of the granular amebocyte from the horseshoe crab,
      Limulus polyphemus.
AB  - The phospholipid composition was determined for the amebocyte of the primitive
      arthropod Limulus polyphemus. The total fatty acid composition of the cells'
      lipids was analyzed by gas chromatography/mass spectrometry (GC/MS) of fatty acid
      methyl esters (FAME). The FAME analysis revealed high levels of 20-carbon
      polyunsaturated fatty acids (PUFA), especially arachidonic (20:4n-6) and
      eicosapentaenoic (20:5n-3) acids. Almost 20% of the total lipid profile was
      comprised of dimethyl acetals of 16- to 20-carbon chain lengths, indicative of
      plasmalogens in the phospholipid pool. Phospholipids, analyzed by high-pressure
      liquid chromatography, included phosphatidylethanolamine (PE),
      phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylinositol (PI),
      sphingomyelin (SPH), and cardiolipin (CL). PE and PC levels predominated at 42.2
      and 36.3%, respectively. Smaller amounts of PS (9.0%) and PI (6.2%) were present,
      as well as low levels of SPH (4.6%), CL (1.6%), and trace amounts of
      lysophosphatidylcholine. The major phospholipid species, PE, PC, PS and PI, were
      collected and their molecular species were examined by electrospray-ionization
      mass spectrometry. The molecular species within the phospholipid classes
      reflected the high levels of PUFA seen in the total lipid profile. PI was mainly
      composed of 18:0a/20:4. Over half of the PS consisted of 18:0a/18:1 and
      18:0a/20:4. The major PE species were 20:1p/20:5, 20:1p/20:4, 18:0p/20:5, and
      18:0p/20:4. PC had the largest distribution of molecular species, and its most
      abundant species were 16:0e/20:5, 16:0e/20:4, and 16:0p/20:4. The presence of
      16:0e/20:4 is the first documentation of a specific precursor to platelet
      activating factor in an invertebrate hemocyte. Note: at the sn-1 position: [a=1=O
      acyl, e = 1-O-alkylether, and p = 1-O-alk-1'-enyl (plasmalogen)].

PMID- 9778143
TI  - Models of antioxidant protection against biological oxidative damage.

PMID- 9778144
TI  - Cyclooxygenase and inflammation in Alzheimer's disease: experimental approaches
      and clinical interventions.
AB  - Many epidemiological studies suggest that use of non-steroidal anti-inflammatory
      drugs (NSAIDs) delay or slow the clinical expression of Alzheimer's disease (AD).
      While it has been demonstrated that neurodegeneration in AD is accompanied by
      specific inflammatory mechanisms, including activation of the complement cascade
      and the accumulation and activation of microglia, the mechanism by which NSAIDs
      might affect these or other pathophysiological processes relevant to AD has been
      unclear. New evidence that cyclooxygenase (COX) is involved in neurodegeneration
      along with the development of selective COX inhibitors has led to renewed
      interest in the therapeutic potential of NSAIDs in AD.

PMID- 9778145
TI  - Responses in the aged rat brain after total immunolesion.
AB  - In the present study, we compare the effects of cholinergic deafferentation of
      the hippocampus, cortex, and olfactory bulb of young and aged rats on nerve
      growth factor (NGF) protein levels in these areas. We also describe glial
      responses to intraventricular injections of the immunotoxin, 192 IgG-saporin in
      the aged. Choline acetyltransferase (ChAT) activity was dramatically decreased in
      the basal forebrain and target areas of the cholinergic basal forebrain neurons
      (CBFNs) in the young immunolesioned rats and to a lesser extent in their aged
      counterparts. After total immunolesion, NGF protein levels significantly
      increased in the hippocampus, cortex, and olfactory bulb of the young rats but
      not of the aged rats, except for small increases in the olfactory bulb after two
      weeks. After immunolesion NGF protein levels in the basal forebrain increased in
      young rats and less so in the aged rats. The total immunolesions had no effects
      on NGF and BDNF mRNA levels in the hippocampus and cortex. Two weeks after
      injection of the immunotoxin, the profiles of AChE- and p75NTR-positive cells
      significantly decreased in medial septum, vertical and horizontal limbs of
      diagonal band and nucleus basalis of Meynert. There was also an increase in
      microglia while but not astrocytes in the subnuclei of basal forebrain. In
      conclusion, 192 IgG-saporin was effective in producing cholinergic lesions in
      both young and aged rat brains, the lesion-induced NGF response was partially
      extinguished in the aged rat brains and immunolesions induced a microglial
      response in aged brain.

PMID- 9778147
TI  - Localization of mRNAs for trkB isoforms and p75 in rat retinal ganglion cells.
AB  - Brain-derived neurotrophic factor (BDNF) plays an important role in the survival
      of retinal ganglion cells (RGCs). To better understand the potential role of BDNF
      receptors in the survival of RGCs, we studied the expression and localization of
      transcripts for trkB isoforms and p75, using reverse transcriptase-polymerase
      chain reaction (RT-PCR) and in situ hybridization with digoxigenin-labeled RNA
      probes in the adult rat retina. We found that truncated trkB and p75 were
      expressed in RGCs, as well as full-length trkB, in the adult rat retina. The
      localization patterns of full-length and truncated trkB mRNAs suggest that a
      subpopulation of RGCs expresses both full-length and truncated trkB. The
      localization pattern of p75 mRNA suggests that it is expressed in a subpopulation
      of RGCs. Expression of both trkB isoforms in RGCs raises the possibility that
      truncated trkB lessens BDNF effect on RGCs by forming nonfunctional heterodimers
      with full-length trkB. This possibility was supported by our observation that
      apoptosis of RGCs detected by the TUNEL method followed close on the onset of
      truncated trkB mRNA expression in the ganglion cell layer of the developing rat
      retina.

PMID- 9778146
TI  - Potentiation of N-methyl-D-aspartate-mediated neurotoxicity by immunostimulated
      murine microglia.
AB  - Microglia have been shown to be immunostimulated by inflammatory cytokines and
      produce a number of toxic mediators. Here we report that immunostimulated
      microglia can synergistically enhance the N-methyl-D-aspartate (NMDA) receptor
      mediated excitotoxicity in rat cerebellar granule cells (CGC) in culture.
      Neurotoxicity was assessed by morphological examination and by measuring the
      release of lactate dehydrogenase and DNA fragmentation. Cultured microglia were
      immunostimulated by interferon-gamma (200 U/ml) and lipopolysaccharides (10
      microg/ml) and one or two days later they were used for co-culture with CGC. Co
      culture of CGC with immunostimulated microglia resulted in a remarkable
      enhancement of the NMDA receptor-mediated death of CGC. This enhanced
      neurotoxicity was mimicked by the nitric oxide releaser 3-morpholinosydnonimine
      (SIN-1) or S-nitroso-N-acetylpenicillamine (SNAP). Superoxide dismutase and
      catalase, which stabilise NO by removing superoxide anion, ameliorated the
      potentiation of the NMDA-mediated death of CGC in co-culture with
      immunostimulated microglia, implying that reactions of NO with superoxide to form
      peroxynitrite can be implicated in the potentiated neurotoxicity. Our data
      indicate that immunostimulated microglia, which may involve in various
      neuropathologies, potentiate the NMDA receptor-mediated excitotoxicity in part
      through the expression of inducible nitric oxide synthase.

PMID- 9778148
TI  - Induction of DNA fragmentation and HSP72 immunoreactivity by adenovirus-mediated
      gene transfer in normal gerbil hippocampus and ventricle.
AB  - Foreign genes have been successfully transferred and expressed in experimental
      animal brains using adenoviral vectors. However, it is not fully understood
      whether adenovirus-mediated gene transfer causes stressful or cytotoxic injury in
      brain. A replication-defective adenoviral vector containing the Escherichia coli
      lacZ gene (AdCMVnLacZ) was directly injected into right hippocampus and lateral
      ventricle of normal gerbil brains. Temporal and spatial profiles of the
      expression of lacZ gene products, DNA fragmentation detected by terminal
      deoxynucleotidyl d-UTP nick end labeling (TUNEL) staining, and heat shock protein
      72 (HSP72) immunoreactivity were examined until 21 days after the injection. In
      the ventricle, lacZ gene was immediately and strongly expressed at 8 hr after the
      injection of AdCMVnLacZ, with a peak at 1-3 days, and disappeared by 21 days.
      Although a small number of choroid plexus cells were TUNEL positive at 3 and 7
      days, no HSP72 immunostaining was observed in the ventricle. Small-to-moderate
      expression of lacZ gene was found in the needle route from 8 hr to 3 days after
      the injection, and a small number of TUNEL-positive cells were detected at the
      needle track at 1-3 days. In the hippocampus, lacZ gene was markedly expressed
      around the dentate gyrus (DG) at 8 hr to 3 days with a peak at 1 day. Large
      number of TUNEL or moderate-to-dense HSP70 staining cells were also detected in
      the same area. CA1 neuronal cells just adjacent to the needle route showed TUNEL
      positivity at 1 to 3 days. However, the TUNEL staining was not associated with
      lacZ gene expression. The majority of lacZ-expressing cells were discriminated
      from the TUNEL-positive cells, whereas some were double-positive with HSP72
      staining in DG. Cellular loss was observed in the CA1 layer around the needle
      route. An apoptotic change was morphologically observed in the marginal region of
      the DG at 1-3 days and in the ventricle at 3-7 days. In the sham control group,
      TUNEL-positive or HSP72-staining cells were only detected around the needle track
      including CA1 cells adjacent to the needle route. These data suggest that
      adenoviral gene transfer may induce direct traumatic injury in the CA1 sector
      near the needle route, indirect apoptotic cell loss in the DG and ventricle, and
      stressful effect on the dentate granule cells in association with adenovirus
      infection in normal gerbil brain.

PMID- 9778149
TI  - QKI expression is regulated during neuron-glial cell fate decisions.
AB  - QKI proteins are expressed by differentiated glia and have been implicated as
      regulators of myelination, but are also thought to function during early neural
      development. This study shows that QKI proteins are expressed in neural
      progenitors of the ventricular zone (vz) during murine CNS development, but that
      their expression is down-regulated during neuronal differentiation. By contrast,
      neural progenitors located in specific subdomains of the vz maintain expression
      of QKI proteins as they differentiate and migrate away into the emerging nervous
      system. These QKI+ cells have characteristics consistent with the acquisition of
      a glial rather than neuronal fate; they express nestin, incorporate BrdU, fail to
      express neuronal markers, and similar QKI+ cells are found in the postnatal
      subventricular zone, a known area of gliogenesis. In vitro, neural progenitor
      cells also down-regulate QKI expression as they differentiate into neurons, but
      not if they differentiate into glia. Furthermore, neural progenitors in strictly
      delineated subdomains of the vz dramatically up-regulate expression of the QKI-5
      isoform prior to the emergence of QKI+ cells from these regions. Taken together,
      these data indicate that (1) glia are generated from subsets of neural
      progenitors found in specific, identifiable subdomains of the vz (2) QKI
      expression is regulated as neural progenitors undergo the neuron-glial cell fate
      decision and (3) QKI expression is a characteristic of glial progenitors.

PMID- 9778150
TI  - Apolipoprotein E4 induces neuronal cell death under conditions of suppressed de
      novo cholesterol synthesis.
AB  - The presence of the apolipoprotein E (apoE) allele epsilon4 is a major risk
      factor for the development of Alzheimer's disease (AD); however, the molecular
      mechanism underlying the acceleration of AD development in individuals with
      epsilon4 remains to be determined. To investigate the isoform-specific effects of
      apoE on neurons, primary neuron cultures were prepared from fetal rat cerebral
      cortices. Inhibition by compactin, a 3-hydroxyl-3-methylglutaryl coenzyme A
      reductase inhibitor of de novo cholesterol synthesis, induced premature neuronal
      cell death in a dose-dependent manner. In the presence of compactin at a
      sublethal dose to the cells, rabbit beta-migrating very low density lipoprotein
      (beta-VLDL) with human apoE4 (the product of epsilon4) induced premature neuronal
      cell death, while that with apoE3 (the product of epsilon3) did not. Neurons
      cultured in the presence of apoE4, beta-VLDL, and compactin were shrunken and
      spherical, containing condensed chromatin and fragmented DNA, features
      characteristic of apoptosis. The addition of intermediate metabolites of the
      cholesterol biosynthetic pathway, including mevalonate and squalene, rescued
      neuronal cells incubated with apoE4 and beta-VLDL, in the presence of compactin.
      These results strongly suggest that a reduction in the level of endogenously
      synthesized cholesterol is a prerequisite for apoE4-induced neuronal cell death.

PMID- 9778151
TI  - Macrophage and microglial responses to cytokines in vitro: phagocytic activity,
      proteolytic enzyme release, and free radical production.
AB  - Certain cytokines are believed to play a key role in the development of
      autoimmune demyelinating diseases. Little is known, however, about the effects of
      these cytokines in the regulation of the key event in myelin destruction, the
      phagocytosis of myelin by phagocytic cells. We investigated the effects of
      certain cytokines and growth factors on cultured peritoneal macrophages and
      microglia in respect to their various functions, phagocytosis, secreted
      proteolytic activity, and oxidative activity. Interferon-gamma (IFN-gamma), tumor
      necrosis factor-alpha (TNF-alpha), and lipopolysaccharide (LPS), all
      proinflammatory factors, actually decreased (IFN-gamma and LPS), or had no effect
      (TNF-alpha) on myelin phagocytosis by macrophages, but substantially increased
      phagocytic activity by microglia. Surprisingly, interleukins 4 and 10 (IL-4 and
      IL-10), considered to be downregulating cytokines, increased phagocytic activity
      by macrophages, while with microglia, IL-4 had no effect, but IL-10 almost
      doubled myelin phagocytosis. Transforming growth factor-beta (TGF-beta) had no
      significant effect on either cell. These cytokines did not affect proteolytic
      secretion in microglia, while IFN-gamma and LPS induced a doubling of the
      secreted proteases. This proteolytic activity was almost completely suppressed by
      calpain inhibitors, although some gelatinase appeared to be present. Microglia
      exerted much more oxidative activity on the membranes than macrophages, and
      granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin 1beta
      (IL-1beta) significantly increased microglial oxidative activity. The pattern of
      responses of macrophages and microglia to the cytokine types indicate that in
      cytokine-driven autoimmune demyelinating disease, microglia may be the more
      aggressive cell in causing tissue injury by phagocytosis and oxidative injury,
      while infiltrating macrophages may produce most of the proteolytic activity
      thought to contribute to myelin destruction.

PMID- 9778153
TI  - Direct administration and utilization of [1-13C]glucose by fetal brain and liver
      tissues under normal and ischemic conditions: 1H, 31P, and 13C NMR studies.
AB  - Three distinct, maternal-independent routes (e.g. intraamniotic, intraperitoneal
      and intracerebral), for [1-13C]glucose utilization by fetal brain and liver
      tissues, were examined by multinuclear magnetic resonance (NMR) spectroscopy
      before and after vascular occlusion of the maternal-fetal blood flow. Labeled
      lactate was the major glycolytic product by all routes, but in addition labeled
      TCA cycle products were also generated. Fractional 13C enrichment in both glucose
      and lactate were always higher in the ischemic state compared to controls using
      either one of the three routes studied. After intraperitoneal injection total
      glucose in the fetal brain was decreased by 85% after 20 min reperfusion
      following 20 min ischemia, but was elevated up to 170% after 60 min. [1
      13C]glucose increased continuously by up to 370% after 60 min. Total glucose in
      the fetal liver remained unchanged while [1-13C]glucose increased up to 380%.
      Total lactate level in brain was 50-80% above the control apart from a transient
      increase (140%) notable after 40 min reperfusion. The kinetics of [3-13C]lactate
      followed a similar time course. At the same time when lactate was transiently
      increased in fetal brain, total lactate as well as 13C-labeled lactate showed a
      transient decrease in liver after 40 min. While the ways of mobilization of
      energy substrates for maintaining adequate metabolic activity in the fetal brain
      remain still unclear, the present 13C NMR studies suggest that both liver glucose
      and lactate can contribute to brain metabolism particularly under ischemic
      stress.

PMID- 9778152
TI  - Monoclonal antibody 14F7, which recognizes a stage-specific immature
      oligodendrocyte surface molecule, inhibits oligodendrocyte differentiation
      mediated in co-culture with astrocytes.
AB  - Cells at an intermediate stage of oligodendrocyte lineage are not only well
      characterized by biochemical studies but also are likely to relate to the outcome
      of physiological events. To elucidate the molecular events leading to the
      development of oligodendrocyte lineage cells, we have raised monoclonal
      antibodies against stage-specific immature oligodendrocytes, which have
      previously been isolated by a novel oligodendrocyte-lineage cell culture
      technique (Sakurai et al.: J Neurosci Res 52:17-26, 1998). We have isolated a
      mouse monoclonal antibody termed 14F7 which predominantly labels stage-specific
      immature oligodendrocytes and have found that the expression of 14F7
      immunoreactivity in the developing neonatal rat forebrain is closely associated
      with cells expressing the oligodendrocyte progenitor marker A2B5 and to immature
      oligodendrocyte expressing O4 antigen. 14F7+ cells were distributed in the
      ventricular and subventricular zone and the nearby forming corpus callosum as non
      myelinating cells. In contrast to cell culture observations, 14F7+ cells were
      seen only in oligodendrocyte lineage cells. For instance, dissociated cell
      culture studies indicated that 14F7 labels a cell surface molecule, and its
      cellular distribution is coincident with all of O4+ cells and A2B5+ cells, and
      even A2B5- cells. By contrast, 14F7-positive cells did not label astrocytes and,
      furthermore, did not label myelin basic protein (MBP)-positive oligodendrocytes.
      14F7 recognized a 48-kDa protein on sodium dodecyl sulfate polyacrylamide gel
      electrophoresis. 14F7 immunoreactivity was detectable in rat brain as early as
      embryonic day 18. Furthermore, in these cells, the total time for differentiation
      was extended, and on maturation, these cells subsequently expressed an array of
      myelin-specific proteins, which normally occurs by direct contact with type-1
      astrocytes. However, in the presence of 14F7, stage-specific oligodendrocytes co
      cultured with astrocytes completely failed to express MBP. These data suggest
      that the 14F7 antigen is a novel cell surface molecule that is expressed in the
      intermediate stage of oligodendrocyte-lineage cells, and it is expected that it
      regulates the differentiation of oligodendrocyte throughout development.

PMID- 9778155
TI  - Lipopolysaccharide differentially regulates microglial trk receptor and
      neurotrophin expression.
AB  - Activated brain microglia play a pivotal role in inflammatory and degenerative
      disorders, mediating immune function and producing toxic and trophic agents. We
      previously reported that microglia express neurotrophins and that neurotrophin-3
      (NT-3) increases microglial proliferation and phagocytosis, processes associated
      with cellular activation. However, mechanisms regulating responsiveness to NT-3
      and expression of NT-3 in activated microglia remain undefined. To investigate
      mechanisms governing microglial responsiveness to neurotrophins, we determined
      whether microglia express trk C, the high-affinity receptor for NT-3, and whether
      the inflammatory agent lipopolysaccharide (LPS) regulates receptor expression.
      Trk C mRNA was expressed by unstimulated microglia, and both trk C mRNA and
      protein were dramatically increased by LPS. In contrast, expression of trk A, the
      high-affinity receptor for nerve growth factor (NGF), was down-regulated by LPS.
      Consequently, the same stimulus differentially influences responsiveness of
      microglia to distinct trophins. In addition, LPS induced microglial NT-3
      expression, suggesting that increases in both the ligand and receptor modulate NT
      3 effects on microglia. Regulation was specific, since brain-derived neurotrophic
      factor (BDNF) and NT-4/5 expression were unaltered by LPS. In sum, our findings
      raise the possibility that microglial NT-3 regulates their response to
      inflammation through autocrine mechanisms: LPS modulates both trk C and NT-3
      which, in turn, regulate microglial function.

PMID- 9778154
TI  - Serotonergic hyperinnervation of the frontal cortex in an animal model of
      depression, the bulbectomized rat.
AB  - We studied the influence of olfactory bulbectomy in rats on three different
      parameters of serotonin (5-HT) presynapses, 5-HT transporter density, tryptophan
      hydroxylase apoenzyme concentration, and the levels of 5-HT and 5-hydroxyindole
      acetic acid (5-HIAA) in various brain regions. Compared with sham-operated
      controls, the Bmax values of [3H]paroxetine binding, the apoenzyme concentration
      of tryptophan hydroxylase and the level of 5-HIAA, and, therefore, the 5-HIAA/5
      HT ratio were significantly and selectively increased in the frontal cortex of
      bulbectomized rats, measured 12 weeks after surgery. The most likely explanation
      of the concomitant increase in levels of all three markers of 5-HT presynapses in
      the frontal cortex is an increased density of 5-HT innervation in this remote
      projection field of the raphe nuclei. It is suggested that the bulbectomy
      associated axotomy of 5-HT fibers projecting to the bulb stimulates collateral
      sprouting and synaptogenesis, especially in the frontal cortex. The resulting 5
      HT hyperinnervation must be expected to alter global neuronal activity in this
      region and to impair the balance of information flow between this and other brain
      regions, resulting in a multitude of secondary behavioral and neurochemical
      changes. The frontocortical abnormalities observed by brain imaging studies in
      the brains of depressed patients may also be explained by a selective 5-HT
      hyperinnervation of this brain region.

PMID- 9778156
TI  - Mupirocin- and methicillin-resistant Staphylococcus aureus spreading in an
      intermediate-care unit in a Brazilian hospital.

PMID- 9778157
TI  - Tuberculosis: what you don't know can hurt you.

PMID- 9778158
TI  - The costs of healthcare worker respiratory protection and fit-testing programs.
AB  - OBJECTIVE: We studied hospital costs associated with healthcare worker (HCW)
      respiratory protection and respirator fit-testing programs recommended by the
      Centers for Disease Control and Prevention (CDC) and mandated by the Occupational
      Safety and Health Administration to decrease nosocomial or occupational
      Mycobacterium tuberculosis (TB). DESIGN: The number and cost of high-efficiency
      particulate air (HEPA)-filter and dust-mist (DM) respirators for 1989 to 1994
      were obtained from study hospital purchasing departments, and the costs of HCW
      fit-testing and education programs for 1994 were estimated from information
      provided by infection control practitioners. Costs of N-class respirator programs
      were estimated for study hospitals using retrospective cost analysis and an
      observational study. SETTING: Four urban hospitals with, and one rural community
      hospital without, documented nosocomial or occupational transmission of multidrug
      resistant TB. RESULTS: During the study period, four of five hospitals introduced
      HEPA and DM respirators and respirator education and fit-testing programs. Median
      costs in 1994 were $83,900 (range, $2,000-$223,000) for respirators and $17,187
      (range, $8,736-$26,175) for respiratory fit-testing programs. The projected
      median annual cost of N95 respirators was $62,023 (range, $270-$422,526).
      CONCLUSIONS: Compliance with CDC TB guidelines may require a substantial
      investment. However, outlays for respirators and education and fit-testing
      programs are more reasonable than would be suggested by analyses that estimated
      the costs of preventing one case of nosocomial TB.

PMID- 9778159
TI  - Nosocomial transmission of a drug-sensitive W-variant Mycobacterium tuberculosis
      strain among patients with acquired immunodeficiency syndrome in Tennessee.
AB  - OBJECTIVE: To use DNA fingerprinting to characterize nosocomial spread of
      Mycobacterium tuberculosis following hospitalization of a patient with acquired
      immunodeficiency syndrome and active pulmonary tuberculosis, for whom respiratory
      isolation was not initiated promptly. DESIGN: Epidemiological investigation.
      SETTING: A tertiary-care medical center in Tennessee. PARTICIPANTS: Patients and
      healthcare workers potentially exposed to the infectious patient in 1992.
      RESULTS: Of 172 healthcare workers exposed, 35 (20%) were judged to have acquired
      tuberculous infection. Risk of acquisition was greatest for nurses and medical
      receptionists. Active tuberculosis later developed in one healthcare worker and
      one hospitalized patient. Nosocomial transmission was supported by
      epidemiological evidence and DNA fingerprinting. The outbreak strain of
      Mycobacterium tuberculosis differed from other isolates at this hospital, but its
      DNA hybridization pattern was highly similar to that of the multidrug-resistant
      outbreak strain W that has been prevalent in New York City, suggesting a common
      strain ancestry. However, the Tennessee isolates were susceptible to all first
      line antituberculous agents. CONCLUSIONS: This report suggests the possibility
      that a molecular characteristic(s) shared by these successful outbreak strains is
      associated with increased transmissibility or pathogenicity and emphasizes the
      need for continued vigilance for tuberculosis in the nosocomial setting.

PMID- 9778160
TI  - The risk of infection associated with intra-arterial catheters for cancer
      chemotherapy.
AB  - OBJECTIVE: To determine the frequency of, and risk factors for, infections
      associated with intra-arterial catheters used for cancer chemotherapy. METHODS:
      Between September 1992 and September 1995, we conducted a surveillance study of
      all 807 intra-arterial catheters placed for chemotherapy at our center. The
      insertion site was disinfected with povidone iodine and alcohol, and the arterial
      catheter was placed using maximal sterile barrier precautions. Upon removal, all
      intravascular segments were submitted for semi-quantitative culture. RESULTS: No
      episodes of catheter-related bloodstream infection (95% confidence interval
      [CI95], 0%-1.6%) were observed. However, the risk of colonization (>15 colony
      forming units) of arterial catheters was 15% (CI95, 12%-17%). Retrospective risk
      factor analysis conducted on 224 intra-arterial catheters placed for chemotherapy
      in 1993 showed that colonization was associated significantly with duration of
      catheterization (median of 1 day for culture-negative catheters vs median of 4
      days for culture-positive catheters, P<.001). Age, gender, prior radiotherapy,
      underlying cancer, neutropenia, and hypoalbuminemia were not associated with
      catheter colonization. CONCLUSION: Intra-arterial catheters for cancer
      chemotherapy placed under maximal sterile barrier precautions for a short period
      of time are associated with a very low risk of bloodstream infection.

PMID- 9778161
TI  - Central venous catheters as a source of hemodialysis-related bacteremia.
AB  - OBJECTIVE: To describe investigations into an increase in hemodialysis-related
      bacteremia that occurred in our hospital in the first 6 months of 1996. SETTING:
      Hemodialysis unit in a tertiary-care medical center. METHODS: Prospective
      surveillance for hemodialysis bacteremia has been performed for several years.
      Cases that occurred in 1995 were compared to cases in the first 6 months of 1996.
      Unit data on dialysis runs and method of dialysis access were used to calculate
      rates. Nested polymerase chain reaction (PCR) was used to type 18 Staphylococcus
      aureus isolates from 1996. A case-control study comparing 80 randomly selected
      hemodialysis patients from 1995 and 1996 was performed to examine infection risk
      factors. RESULTS: The hemodialysis bacteremia rate was 1.2 per 1,000 runs in 1995
      and 2.8 per 1,000 in the first 6 months of 1996 (P=.0009). The 25 cases in 1995
      and 32 in the first half of 1996 were similar in age, gender, means of vascular
      access, and microbial etiology. Central venous catheter (CVC) access accounted
      for >90% of cases in both time periods. S aureus was the most common microbial
      etiology (53% of the 1996 cases). PCR typing of S aureus isolates from 1996
      demonstrated five different strains, the most common having six isolates. The use
      of CVCs as a means of vascular access abruptly increased in the unit in January
      1996, from <30% of dialysis runs in 1995 to >40% in 1996 (P<.001), associated
      with structural changes in healthcare delivery in the region resulting in delays
      in performing surgical procedures, such as creation of vascular grafts and
      fistulae. CONCLUSION: A marked increase in hemodialysis bacteremia occurred in
      1996, associated with increased reliance on CVCs for vascular access in
      hemodialysis patients during a period of healthcare restructuring.

PMID- 9778162
TI  - Failure to eradicate vancomycin-resistant enterococci in a university hospital
      and the cost of barrier precautions.
AB  - OBJECTIVE: To describe the effect of infection control interventions on the
      incidence of vancomycin-resistant enterococci (VRE), the utility of pharyngeal
      cultures for surveillance for VRE colonization, and the cost of barrier
      precautions. DESIGN: Evaluation of the occurrence of VRE infection or
      colonization, rates of vancomycin use, results of surveillance cultures before
      and after interventions, and the cost of increased barrier precautions. SETTING:
      University of Massachusetts Medical Center, a 347-bed tertiary-care teaching
      hospital with eight intensive-care units, one burn unit, and one bone marrow
      transplant unit. PARTICIPANTS: Patients in the intensive-care units and staff who
      were involved with patients colonized or infected with VRE. METHODS: Infection
      control interventions included placement of patients with VRE in private rooms,
      strict contact isolation, cohorting of patient and nursing staff, prohibiting of
      equipment sharing, and monitoring of compliance with the vancomycin restriction
      policy, with hand washing, and of the adequacy of environmental cleaning. Both
      rectal and pharyngeal cultures were obtained from patients at the beginning of
      the outbreak, and the utility of pharyngeal cultures was evaluated. The cost of
      barrier precautions was estimated by comparing the cost of glove and gown use
      before and after the outbreak began. RESULTS: The interventions decreased the
      number of new cases of VRE, but total eradication of VRE was not achieved.
      Compliance with the room-cleaning protocol was 91% (141/155 observations). Hand
      washing following interaction with patients who were not in isolation was 51%, vs
      100% for patients in isolation. Overall, handwashing compliance was 71%
      (319/449): 56% (130/231) for physicians and 86% (187/218) for nurses (P<.0001).
      The mean number of doses of vancomycin dispensed per 1,000 patient days decreased
      from 145 to 114 per 1,000 patient days (P<.001). Compliance with vancomycin-use
      guidelines was 85%. Forty-six (77%) of 60 surveillance rectal swabs yielded
      enterococci, as compared to only 4 (11%) of 36 pharyngeal cultures (P<.0001).
      Expenses on glove and gowns alone increased by over $11,000 per year since the
      epidemic began. CONCLUSIONS: Implementation of the various infection control
      measures did not eradicate VRE cases from the hospital. Rectal cultures were more
      useful than pharyngeal cultures for surveillance of VRE. Controlling VRE
      epidemics can be costly.

PMID- 9778163
TI  - Use of amoxicillin-clavulanate and resistance in Escherichia coli over a 4-year
      period.
AB  - OBJECTIVE: To reduce the use of amoxicillin-clavulanate after high-resistance
      rates in Escherichia coli were detected. DESIGN: Intervention study; the
      interventions were introduced successively over a 4-year period while closely
      monitoring the resistance patterns. SETTING: A 260-bed acute-care hospital in
      Switzerland. INTERVENTIONS: Introduction of therapeutic guidelines for specific
      departments or indications, which proposed alternative antibiotics to amoxicillin
      clavulanate. The perioperative prophylactic use of amoxicillin-clavulanate was
      eliminated completely. RESULTS: The absolute amount of amoxicillin-clavulanate
      consumed decreased by 23%, from 24.8 g per 100 patient days in 1992 to 18.5 g per
      100 patient days in 1995. The number of courses, a parameter that takes the
      prophylactic use into account, decreased by 62% from 2.3 per 100 patient days in
      1992 to 0.9 per 100 patient days in 1995. The percentage of sensitive strains
      increased from 54.9% (n=512) in 1992 and 54.0% (n=506) in 1993 to 72.1% (n=546)
      in 1994 and 83.1% (n=668) in 1995. No major changes were detected for other
      antimicrobials, such as cotrimoxazole, tetracycline, or cefuroxime, used in this
      4-year period. CONCLUSIONS: A decrease in the use of amoxicillin-clavulanate was
      followed by an increase in susceptibility of E coli to it. It was not possible to
      prove a causative relationship. Only a temporal association was discovered. The
      reduction of the use of amoxicillin-clavulanate was achieved through the
      implementation of treatment guidelines, facilitated through a close collaboration
      among the clinical pharmacists, the infection control practitioner, the
      microbiology laboratory, and the physicians in charge of the respective
      departments.

PMID- 9778164
TI  - Simplified surveillance for nosocomial bloodstream infections.
AB  - OBJECTIVE: To compare a surveillance definition of noso comial bloodstream
      infections requiring only microbiology data to the Centers for Disease Control
      and Prevention's (CDC) current definition. SETTING: Six teaching hospitals.
      METHODS: We classified a representative sample of 73 positive blood cultures from
      six hospitals growing common skin contaminant isolates using a definition for
      bacteremia requiring only microbiology data and the CDC definition for primary
      bloodstream infection (National Nosocomial Infections Surveillance [NNIS] System
      review method). The classifications assigned during routine prospective
      surveillance also were noted, and the time required to classify isolates by the
      two methods was compared. RESULTS: Among 65 blood cultures growing common skin
      contaminant isolates obtained from adults, the agreement rate between the
      microbiology data method and the NNIS review method was 91%. Agreement was
      significantly poorer for the eight blood cultures growing common skin contaminant
      isolates obtained from pediatric patients. The microbiology data method requires
      approximately 20 minutes less time per isolate than does routine surveillance.
      CONCLUSIONS: A definition based on microbiology data alone yields the same result
      as the CDC's definition in the large majority of instances. It is more resource
      efficient than the CDC's current definition.

PMID- 9778165
TI  - Importance of the surveillance method: national prevalence studies on nosocomial
      infections and the limits of comparison.
AB  - OBJECTIVE: To demonstrate the limits of comparison of national prevalence rates
      of nosocomial infections. DESIGN AND SETTING: Critical analysis of prevalence
      rates and methods of the Nosocomial Infections in Germany (NIDEP) study and other
      prevalence surveys with particular attention to the selection of patients, the
      qualification and training of the investigators, and the methods of identifying
      nosocomial infections. RESULTS: The lowest prevalence rate was found in Germany
      (3.5%), the highest in Belgium (9.3%). These differences may not be accurate,
      because variations in methods allow for differing explanations. CONCLUSIONS:
      Because of numerous methodological factors, comparison of infection rates between
      countries should be avoided. In contrast to other prevalence studies, the
      methodology of the German-NIDEP study permits registration of only certain
      infections, which is the main reason for the low rate.

PMID- 9778166
TI  - Experience with two validation methods in a prevalence survey on nosocomial
      infections.
AB  - OBJECTIVE: To determine whether an investigator effect remained on the first
      German study on the prevalence of nosocomial infections Nosokomiale Infektionen
      in Deutschland Erfassung und Pravention (NIDEP), despite extensive validation
      efforts. DESIGN: Two validation methods were applied: bedside validation and
      validation by case studies. In both cases, the results of the four investigators
      were compared with the diagnosis of gold standard observers. SETTING: Validation
      measures were applied before, intermittently, during, and at the end of the
      surveillance period in 72 acute-care hospitals with 14,966 patients. RESULTS: The
      overall sensitivity in the bedside-validation periods was 89.0%; the overall
      specificity was 99.5%. For validation by case studies, overall sensitivity was
      95.6%, and overall specificity was 92.8%. At the end of the surveillance, a
      remarkable investigator effect was found. CONCLUSION: Despite validation results
      that were assessed as satisfactory, based on available literature, an
      investigator effect was observed. This underlines the need for data validation
      and the formulation of recommendations for data validation. Clarification of the
      Centers for Disease Control and Prevention criteria for pneumonia and primary
      bloodstream infection and the inclusion of some diagnostic test results may
      reduce or prevent an investigator effect in future studies.

PMID- 9778167
TI  - Klebsiella pneumoniae bloodstream infections in neonates in a hospital in the
      Kingdom of Saudi Arabia.
AB  - OBJECTIVE: To identify risk factors for Klebsiella pneumoniae bloodstream
      infections (BSI) in neonates in a hospital in the Kingdom of Saudi Arabia (KSA).
      DESIGN: Two case-control studies among hospitalized neonates during February 15
      May 14, 1991, and a procedural and microbiological investigation. SETTING:
      Hospital A, a maternity and children's hospital in KSA. PATIENTS: Case patients
      had a blood culture positive for K pneumoniae after >2 days of hospitalization
      and had no evidence of a nonblood primary site of infection. RESULTS: When the 20
      case patients were compared with controls, hospitalization in a critical-care
      unit (odds ratio [OR], 5.5; 95% confidence interval [CI95], 1.20-51.1; P=.03) was
      identified as a risk factor. When the case patients were compared with a second
      set of controls matched by critical-care status, receipt of a particular
      intravenous fluid (D10%/0.2NS; OR, 11.0; CI95, 1.42-85.2; P=.009) or a blood
      product (OR undefined; P=.04) were identified as risk factors. Infusates were
      administered via umbilical catheters for most case and control patients (19/20 vs
      15/20, P>.05); catheters were manipulated more frequently in patients in critical
      care units. Umbilical catheter tip, skin, or mucus membrane K pneumoniae
      colonization occurred in 47% and 53% of evaluated case and control patients,
      respectively. Available K pneumoniae isolates from blood cultures and
      colonization sites had identical antimicrobial susceptibility patterns. Emphasis
      on handwashing, careful preparation and administration of infusates, and aseptic
      technique for catheter insertion, maintenance, and manipulation was temporally
      associated with resolution of the epidemic. CONCLUSIONS: This outbreak was
      probably due to infusion therapy practices that led to BSI in nursery patients
      colonized with K pneumoniae. Both catheter-related infections and extrinsic
      contamination of infusates may have occurred. Hospital personnel should be aware
      of their potential to spread nosocomial pathogens from person to person and
      should implement Centers for Disease Control and Prevention recommendations to
      decrease nosocomial BSIs.

PMID- 9778168
TI  - The kin-cohort study for estimating penetrance.
AB  - A cross-sectional study may be more feasible than a cohort or case-control study
      for examining the effect of a genetic mutation on cancer penetrance outside of
      cancer families. The kin-cohort design uses volunteer probands selected from a
      population with a relatively high frequency of the mutations of interest. By
      considering the cancer risk in first-degree relatives of mutation-positive and 
      negative probands as a weighted average of the risk in carriers and noncarriers,
      with weights calculated assuming a known mode of inheritance, one can infer the
      penetrance of the mutations. The estimates of penetrance by age 70 years for
      three specific mutations in the BRCA1 and BRCA2 genes common among Ashkenazi Jews
      for the first occurrence of breast or ovary cancer is 63%. The kin-cohort design
      can be a useful tool for quickly estimating penetrance from volunteers in a
      setting in which the mutation prevalence is relatively high.

PMID- 9778169
TI  - Use of two-segmented logistic regression to estimate change-points in
      epidemiologic studies.
AB  - In many epidemiologic data, the dose-response relation between a continuous
      exposure and the risk of disease abruptly changes when the exposure variable
      reaches an unknown threshold level, the so-called change-point. Although several
      methods are available for dose-response assessment with dichotomous outcomes,
      none of them provide inferential procedures to estimate change-points. In this
      paper, we describe a two-segmented logistic regression model, in which the linear
      term associated with a continuous exposure in standard logistic regression is
      replaced by a two-segmented polynomial function with unknown change-point, which
      is also estimated. A modified, iteratively reweighted least squares algorithm is
      presented to obtain parameter estimates and confidence intervals, and the
      performance of this model is explored through simulation. Finally, a two
      segmented logistic regression model is applied to a case-control study of the
      association of alcohol intake with the risk of myocardial infarction and compared
      with alternative analyses. The ability of two-segmented logistic regression to
      estimate and provide inferences for the location of change-points and for the
      magnitude of other parameters of effect will make this model a useful complement
      to other methods of dose-response analysis in epidemiologic studies.

PMID- 9778170
TI  - Validity of methods used to assess vitamin and mineral supplement use.
AB  - Assessing vitamin and mineral supplement use is important because supplement use
      per se is an exposure of interest for the risk of several chronic diseases and
      because supplements contribute a large proportion of total (diet plus supplement)
      micronutrient intake, another important exposure in epidemiologic research.
      Unfortunately, little is known about methods for obtaining valid information
      about supplement use. The authors conducted a validation study in 1996 comparing
      supplement data collected in a telephone interview and from a self-administered
      questionnaire with data derived from a detailed, in-person interview and
      transcription of the labels of supplement bottles (i.e., a gold standard) among
      adult supplement users in Washington State (n = 104). Spearman correlation
      coefficients comparing average daily supplemental vitamin and mineral intake from
      the interview or questionnaire with the gold standard ranged from 0.76 (95%
      confidence interval 0.66-0.83) for vitamin C to 0.08 (95% confidence interval 
      0.14 to 0.29) for iron, with a mean of about 0.5. The principal sources of error
      were inaccurate assumptions about the micronutrient composition of multiple
      vitamins and respondent confusion regarding the distinction between multiple
      vitamins and single supplements. These results suggest that commonly used
      epidemiologic methods of assessing supplement use may incorporate significant
      amounts of error in estimates of some nutrients.

PMID- 9778172
TI  - Foot pain and disability in older women.
AB  - In a study of the relation between foot pain and disability, a cross-sectional
      analysis was performed using baseline data (1992-1995) from the Women's Health
      and Aging Study, a population-based study of 1,002 disabled women aged 65 years
      and older living in Baltimore, Maryland. Chronic and severe foot pain, defined as
      pain lasting 1 month or longer in the previous year, plus pain in the previous
      month rated severe (7-10 on a scale of 0 to 10), was reported by 14% of the
      women. Severe foot pain was more common in women who were younger (aged 65-74
      years), obese, or had hand or knee osteoarthritis. Walking speed and five
      repeated chair stands were slower in women with foot pain. After adjustment for
      age, body mass index, race, education, self-rated health, smoking status,
      comorbidities, and number of other pain sites, severe foot pain was independently
      associated with increased risk for walking difficulty (adjusted odds ratio =
      1.69, 95% confidence interval 1.10-2.59) and disability in activities of daily
      living (adjusted odds ratio = 1.91, 95% confidence interval 1.21-3.01). These
      findings suggest that severe foot pain may play a key role in disability in older
      women. Further studies are warranted to confirm these results longitudinally and
      to determine whether interventions to alleviate foot pain could reduce or prevent
      disability in older women.

PMID- 9778171
TI  - Birth weight and renal disease in Pima Indians with type 2 diabetes mellitus.
AB  - Congenital retardation of renal development may increase the risk of renal
      disease, and this risk may be enhanced by diseases, such as diabetes, that damage
      the kidney. In this study, the prevalence of urinary albumin excretion,
      determined in 308 Pima Indians with type 2 diabetes, was 63% in subjects with low
      birth weight (<2,500 g), 41% in those with normal birth weight (2,500-4,499 g),
      and 64% in those with high birth weight (> or =4,500 g). When examined as a
      continuous variable by generalized additive logistic regression, birth weight had
      a U-shaped association with the prevalence of elevated urinary albuminuria (p =
      0.04) after adjustment for age, sex, duration of diabetes, glycosylated
      hemoglobin, and blood pressure. The odds of elevated albuminuria in subjects of
      low birth weight was 2.3 times (95% confidence interval 0.72-7.2) that in
      subjects of normal birth weight, and the odds in subjects of high birth weight
      was 3.2 times (95% confidence interval 0.75-13.4) as high. Sixty-four percent of
      the subjects with high birth weight and none of those with low birth weight were
      offspring of diabetic mothers. After maternal diabetes during pregnancy was
      controlled for, the odds of elevated albuminuria in subjects of high birth weight
      was no longer higher (odds ratio = 1.0, 95% confidence interval 0.22-4.9). The
      higher prevalence of elevated albuminuria in diabetic Pima Indians with high
      birth weight may be due to intrauterine diabetes exposure, whereas the higher
      prevalence in those with low birth weight may be due to the effects of
      intrauterine growth retardation.

PMID- 9778173
TI  - Assessing diagnostic classification in an emergency department: implications for
      daily time series studies of air pollution.
AB  - Seven independent assessments of diagnosis were obtained for 92 records of
      nontrauma emergency department visits in Saint John, New Brunswick, Canada, in
      1994. The hospital database was 1.18 times as likely (p < 0.05) as six external
      physician raters to classify visits as cardiorespiratory, which was consistent
      for high- and low-pollution days. Kappa was 0.70 (95 percent confidence interval
      (CI) 0.68-0.73). Kappajs were: asthma, 0.69 (95% CI 0.64-0.73); chronic
      obstructive pulmonary disease, 0.78 (95% CI 0.74-0.83); respiratory infections,
      0.53 (95% CI 0.49-0.57); cardiac, 0.84 (95% CI 0.79-0.88); and other, 0.66 (95%
      CI 0.62-0.71). Substantial or better interobserver agreement was seen,
      respiratory infections notwithstanding, and there was no evidence of diagnostic
      bias in relation to daily air pollution level.

PMID- 9778174
TI  - Trends of back pain in eastern Finland, 1972-1992, in relation to socioeconomic
      status and behavioral risk factors.
AB  - The aim of this study was to compare the trends in the prevalence of back pain
      between several population subgroups and to assess the stability of the
      associations between back pain and its potential risk factors. Five cross
      sectional surveys with independent random samples were conducted in two provinces
      in eastern Finland every fifth year from 1972 to 1992. There were 29,043
      respondents aged 30-59 years. The respondents completed a questionnaire that
      asked about the occurrence of back pain during the preceding month. The
      prevalence of back pain varied between 46 and 50 percent among men and between 46
      and 51 percent among women. In general, the trend for the entire sample was
      fairly stable, but the prevalence rates seemed to differ considerably between
      subgroups of the population. Back pain was more prevalent among those with lower
      education and income, those with blue-collar occupations, and those doing heavy
      work. The trends were significantly inconsistent (p < 0.05), for example, between
      the categories according to household income and, among men, between the
      categories according to body mass index, a suspected risk factor for back pain.

PMID- 9778175
TI  - Reproductive risk factors for breast cancer in Hispanic and non-Hispanic white
      women: the New Mexico Women's Health Study.
AB  - The authors conducted a population-based case-control study of breast cancer in
      Hispanic women in New Mexico. Hispanic and non-Hispanic white women with incident
      breast cancer, aged 30-74 years and diagnosed between 1992 and 1994, were
      identified by the New Mexico Tumor Registry. Controls were selected using random
      digit dialing and frequency matched by ethnicity, age, and region. Information on
      reproductive history, lactation, and other risk factors was collected through in
      person interviews; 719 Hispanics and 836 non-Hispanic whites were included in the
      analysis. Conditional logistic regression was used to estimate relative risk of
      breast cancer for reproductive factors and to assess ethnic differences in
      effects. Older age at first full-term birth was associated with breast cancer
      among Hispanics; the odds ratio for women aged 27 years and older at first full
      term birth compared with women 18 years or younger was 2.26 (95% confidence
      interval 1.17-4.38) compared with 1.60 (95% confidence interval 0.86-3.01) for
      non-Hispanic whites. Higher parity was associated with reduced risk of breast
      cancer for non-Hispanic whites, but not Hispanics (p < 0.008). Longer lactation
      was associated with reduced risk in premenopausal Hispanic women and
      premenopausal and postmenopausal non-Hispanic white women. Reproductive factors
      explained 17% of the ethnic difference in breast cancer incidence for
      postmenopausal women and none of the difference for premenopausal women.

PMID- 9778176
TI  - Occupational chlorophenol exposure and soft tissue sarcoma risk among men aged 30
      60 years.
AB  - To evaluate the association of chlorophenol exposure with soft tissue sarcoma
      risk independent of phenoxyherbicide exposure, the authors analyzed data from the
      Selected Cancers Study, a population-based case-control study that included 295
      male soft tissue sarcoma cases, aged 32-60 years, from eight population-based
      cancer registries and 1,908 male controls. Chlorophenol exposure was assigned
      using both an intensity and a confidence estimate by an industrial hygienist
      based on verbatim job descriptions. Seventeen percent of the jobs rated as high
      intensity involved wood preservation, while 82% involved cutting oils. Soft
      tissue sarcoma risk, modeled using conditional logistic regression, was
      significantly associated with ever having high-intensity chlorophenol exposure
      (odds ratio = 1.79, 95% confidence interval 1.10-2.88). A duration-response trend
      was evident among more highly exposed subjects (p for trend < 0.0001). For
      subjects with 10 or more years of substantial exposure, the odds ratio was 7.78
      (95% confidence interval 2.46-24.65). These results suggest that chlorophenol
      exposure independent of phenoxyherbicides may increase the risk of soft tissue
      sarcoma. Because of the large number of machinists in the exposed group and the
      complex composition of cutting fluids, it is possible that another exposure
      involved in machining is responsible for the observed excess risk.

PMID- 9778177
TI  - Drinking water mutagenicity and urinary tract cancers: a population-based case
      control study in Finland.
AB  - The detection of mutagenic and carcinogenic chlorination by-products in
      chlorinated drinking water has raised concern in many countries over the
      potential health effects of long-term exposure to these products. The relation
      between estimated exposure to historical drinking water mutagenicity and cancer
      was studied in Finland by using a population-based case-control study comprising
      732 bladder cancer cases, 703 kidney cancer cases, and 914 controls. The cases
      were obtained from the nationwide Finnish Cancer Registry for the years 1991
      1992. The controls, frequency matched by age and sex, were randomly selected from
      the national population registry. Information on past drinking water sources and
      confounding factors was acquired through a questionnaire. Historical exposure to
      drinking water mutagenicity was estimated by using information on past residence,
      past water source, and historical data on water quality and treatment. Odds
      ratios were calculated for an increase of 3,000 net revertants per liter (net
      rev/liter) in average exposure from 1950 to 1987, adjusting for age, sex,
      socioeconomic status, and smoking in logistic regression models. A small,
      statistically significant, exposure-related excess risk was found for kidney
      cancer for men (odds ratio = 1.49, 95 percent confidence interval (CI) 1.05-2.13)
      for 3,000 net rev/liter exposure level. For women, the association remained
      nonsignificant, with a lower odds ratio of 1.08 (95% CI 0.69-1.68). For bladder
      cancer, the odds ratio for both men and women was 1.22 (95% CI 0.92-1.62) for
      3,000 net rev/liter exposure. However, a higher odds ratio of 2.59 (95% CI 1.13
      5.94) for 3,000 net rev/liter exposure was observed for male nonsmokers.

PMID- 9778178
TI  - Re: "High rates of HIV infection among injection drug users participating in
      needle exchange programs in Montreal: results of a cohort study".

PMID- 9778179
TI  - Re: "Invited commentary: le mystere de Montreal".

PMID- 9778180
TI  - Re: "Invited commentary: le mystere de Montreal".

PMID- 9778181
TI  - Role of potassium channels in regulation of cerebral vascular tone.

PMID- 9778182
TI  - Simultaneous glutamate and perfusion fMRI responses to regional brain
      stimulation.
AB  - Functional magnetic resonance imaging (fMRI) rests on the assumption that
      regional brain activity is closely coupled to regional cerebral blood flow (rCBF)
      in vivo. To test the degree of coupling, cortical brain activity was locally
      stimulated in rats by reversed microdialysis infusion of picrotoxinin, alphagamma
      aminobutyric acid-A antagonist. Before and during the first 30 minutes of
      infusion, simultaneous fMRI (rCBF) and neurochemical (interstitial glutamate
      concentration) measures of brain activity were highly correlated (r = 0.83).
      After 30 minutes of picrotoxinin-induced stimulation, glutamate levels decreased
      but rCBF remained elevated, suggesting that additional factors modulate the
      relationship between neuronal neurotransmitters and hemodynamics at these later
      stages.

PMID- 9778183
TI  - Prolonged therapeutic window for ischemic brain damage caused by delayed caspase
      activation.
AB  - Apoptotic cell death is prominent in neurodegenerative disorders, such as
      Alzheimer's disease and Huntington's disease, and is found in cerebral ischemia.
      Using a murine model of delayed cell death, we determined that cleavage of zDEVD
      amino-4-trifluoromethyl coumarin (zDEVD-afc) in brain homogenate, a measure of
      caspase activation, increased initially 9 hours after brief (30 minutes) middle
      cerebral artery occlusion along with caspase-3p20 immunoreactive cleavage product
      as determined by immunoblotting. zDEVD-afc cleavage activity was blocked by
      pretreatment or posttreatment with the caspase-inhibitor N-benzyloxycarbonyl
      Asp(OMe)-Glu(OMe)-Val-Asp(OMe)-fluoromethyl-ketone (zDEVD-fmk), and ischemic
      damage was reduced when the drug was injected up to 9 hours after reperfusion.
      The protection was long lasting (21 days). Hence, the period before caspase
      activation defined the therapeutic opportunity for this neuroprotective agent
      after mild ischemic brain injury. Prolonged protection after caspase inhibition
      plus the extended treatment window may be especially relevant to the treatment of
      neurodegenerative disorders.

PMID- 9778184
TI  - Neuronal stress response and neuronal cell damage after cardiocirculatory arrest
      in rats.
AB  - Cardiocirculatory arrest is the most common clinical cause of global cerebral
      ischemia. We studied neuronal cell damage and neuronal stress response after
      cardiocirculatory arrest and subsequent cardiopulmonary resuscitation in rats.
      The temporospatial cellular reactions were assessed by terminal
      deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling (TUNEL)
      staining of DNA fragments, in situ hybridization (heat shock protein hsp70;
      immediate early genes c-fos and c-jun), and immunocytochemical (HSP70; and
      myeloperoxidase, specific marker of polymorphonuclear leukocytes [PMNL])
      techniques. Cardiac arrest of 10 minutes' duration was induced in mechanically
      ventilated male Sprague-Dawley rats anesthetized with nitrous oxide and
      halothane. After cardiopulmonary resuscitation, animals were allowed to reperfuse
      spontaneously for 6 hours, 24 hours, 3 days, and 7 days (n = 6 per group). Five
      sham-operated animals were controls. The TUNEL staining revealed an early onset
      degeneration in the thalamic reticular nucleus (TRN) at 6 hours that peaked at 3
      days. In contrast, degeneration was delayed in the hippocampal CA1 sector,
      showing an onset at 3 days and a further increase in the number of TUNEL-positive
      cells at 7 days. A minor portion of TUNEL-positive nuclei in the CA1 sector
      showed condensed chromatin and apoptotic bodies, whereas all nuclei in the TRN
      revealed more diffuse staining. After 6 hours of reperfusion, levels of mRNA for
      hsp70 and c-jun were elevated in circumscribed areas of cortex, in all
      hippocampal areas, and in most nuclei of thalamus, but not in the TRN. After 24
      hours, a strong expression of mRNA for hsp70 and c-jun could be observed in the
      second layer of the cortex and in hippocampal CA1 sector; hsp70 also was observed
      in hippocampal CA3 sector. Some animals showed expression of hsp70 and c-jun in
      the dentate gyrus. After 3 days, hsp70 and c-jun were detected mainly in the CA1
      sector of hippocampus. At 7 days, mRNA for both returned to control values.
      Therefore, delayed cell degeneration in the CA1 sector corresponds to a prolonged
      expression of hsp70 and c-jun in this area. In situ hybridization studies for c
      fos revealed a strong signal in CA3 and dentate gyrus and a less prominent signal
      in TRN at 6 hours. At 24 hours, CA4 and amygdalae were positive, whereas at 3 and
      7 days, the signal reached control levels; no prolonged or secondary expression
      was observed in the CA1 sector. Immunohistochemical study confirmed translation
      of HSP70 in various areas corresponding to the detection of mRNA, including the
      CA1 sector. The number of PMNL increased significantly at 6 hours and 7 days
      after cardiac arrest; PMNL were distributed disseminately and were not regionally
      associated with neuronal cell damage. The current data support the view that CA1
      neurons might undergo an apoptosis-associated death after cardiac arrest, but
      PMNL are not directly involved in this process. The marked differences in the
      time course and the characteristics of TUNEL staining and the neuronal stress
      response in CA1 sector and TRN point to different mechanisms of neuronal injury
      in the two selectively vulnerable areas.

PMID- 9778186
TI  - Evaluation of a motor deficit after chronic focal cerebral ischemia in rats.
AB  - It is well known that hemiplegia is frequently observed in cerebral ischemia. It
      is important for the pathophysiologic study and development of drug therapies to
      establish a precise method investigating impairment of motor function with animal
      models. To develop a quantitative and objective method for evaluating impairment
      of motor function, we examined an inclined plane test after chronic focal
      cerebral ischemia in the rat. Standard scoring of neurologic deficits has
      limitations, including problems with quantification and objectivity. The purpose
      of this study was to establish a novel method for evaluating impairment of motor
      function in middle cerebral artery (MCA) occluded rats. The left MCA was
      permanently occluded at a proximal site, and sensorimotor performance was
      evaluated at the fifth day and every week for 11 weeks thereafter. The ability to
      maintain body position on an inclined plane was measured when rats were placed on
      a stainless steel slope in left-headed, right-headed, and up-headed positions.
      Neurologic examination based on hemiparesis and abnormal posture was also
      performed. After all behavioral examinations were completed, the degree of
      shrinkage of the left hemisphere to the contralateral was measured. The ability
      of MCA-occluded rats to maintain position on an inclined plane in the left-headed
      position was significantly restricted when compared with that of sham-operated
      rats throughout the test period (maximum angle of 37 degrees versus 45 degrees,
      respectively). Minimal natural recovery was observed for all position
      measurements. MCA-occluded rats showed a significantly higher neurologic score
      with natural recovery. The ability to maintain position on an inclined plane
      after MCA occlusion (MCAO) was significantly correlated with the degree of the
      shrinkage of the ischemic hemisphere and neurologic score. The angle for the left
      headed position was most strongly correlated with ipsilateral shrinkage. In the
      present study, long-lasting impairment of motor function was detected in rats
      with MCAO, which correlated with the shrinkage of the ischemic hemisphere.
      Furthermore, a difference in performance depending on body position (left-headed
      versus right-headed) was also detected. The left-headed position was found to be
      most sensitive for evaluating this model. The inclined plane test is a
      quantitative, objective, and sensitive method for evaluating motor deficits after
      chronic focal cerebral ischemia in rats, and this method may be useful to
      investigate changes in motor function in hemiplegia.

PMID- 9778185
TI  - Postischemic enhancements of N-methyl-D-aspartic acid (NMDA) and non-NMDA
      receptor-mediated responses in hippocampal CA1 pyramidal neurons.
AB  - Glutamate receptor-mediated responses were investigated by using a whole-cell
      recording and an intracellular calcium ion ([Ca2+]i) imaging in gerbil
      postischemic hippocampal slices prepared at 1, 3, 6, 9, 12, and 24 hours after 5
      minute ischemia. Bath application of N-methyl-D-aspartic acid (NMDA), alpha-amino
      3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), and kainate showed that NMDA-,
      AMPA- and kainate-induced currents were enhanced in postischemic CA1 pyramidal
      neurons at 1 to 12 hours after 5-minute ischemia. NMDA and non-NMDA receptor
      mediated excitatory postsynaptic currents (EPSC) were examined in postischemic
      CA1 pyramidal neurons at 3 hours after 5-minute ischemia to confirm whether
      synaptic responses are enhanced in the postischemic CA1 pyramidal neurons. The
      amplitudes of NMDA- and non-NMDA-receptor-mediated EPSC were enhanced in the
      postischemic CA1 pyramidal neurons. NMDA-, AMPA-, and kainate-induced [Ca2+]i
      elevations were also examined to determine whether the enhancement of currents is
      accompanied by the enhancement of [Ca2+]i elevation. The enhancements of NMDA-,
      AMPA-, and kainate-induced [Ca2+]i elevations were shown in the postischemic CA1.
      These results indicate that NMDA and non-NMDA receptor-mediated responses are
      persistently enhanced in the CA1 pyramidal neurons 1 to 12 hours after transient
      ischemia, and suggest that the enhancement of glutamate receptor-mediated
      responses may act as one of crucial factors in the pathologic mechanism
      responsible for leading postischemic CA1 pyramidal neurons to irreversible
      neuronal injury.

PMID- 9778187
TI  - Delayed treatment with aminoguanidine decreases focal cerebral ischemic damage
      and enhances neurologic recovery in rats.
AB  - Delayed treatment with aminoguanidine (AG), a relatively selective inhibitor of
      inducible nitric oxide synthase, ameliorates brain damage produced by occlusion
      of the rat's middle cerebral artery (MCA). We investigated whether the protection
      exerted by AG is dose-dependent and whether it is associated with improved
      neurologic outcome. We also studied the effect of the timing of administration of
      AG relative to the induction of cerebral ischemia. Halothane-anesthetized
      spontaneously hypertensive rats underwent permanent MCA occlusion distal to the
      lenticulostriate branches. Neurologic deficits were assessed daily by the
      postural reflex test and beam balance test. Infarct volume was determined in
      thionin- stained sections 96 hours after ischemia and values corrected for
      swelling. Treatment with AG (intraperitoneally, twice daily), starting 24 hours
      after MCA occlusion, decreased neocortical infarct volume in comparison to
      vehicle-treated rats. After correction for swelling, the decrease was 8 +/- 12%
      at 50 mg/kg (n = 8; P > .05; analysis of variance), 25 +/- 13% at 100 mg/kg (n =
      7; P < .05), 30 +/- 16% at 200 mg/kg (n = 7; P < .05) and 32 +/- 9% at 400 mg/kg
      (n = 5; P < .05). Twenty-four hours after induction of ischemia neurologic
      deficits scores did not differ between treated and untreated rats (P > .05).
      However, from 48 to 96 hours after ischemia, neurologic deficits improved
      significantly in rats treated with AG (100 to 400 mg/kg) compared to rats in
      which vehicle was administered (P < .05). The decrease in neocortical infarct
      volume was greatest when AG (100 mg/ kg; twice daily) was administered 12 (26 +/-
      17%; n = 9) or 24 hours (25 +/- 13, n = 7) after MCA occlusion. The findings show
      that AG decreases ischemic brain damage dose-dependently and improves neurologic
      recovery. Delayed treatment with AG may be a therapeutic strategy to selectively
      target the evolution of ischemic damage that occurs in the post-ischemic period.

PMID- 9778188
TI  - Spatial stability of extracellular potassium ion and blood flow distribution in
      rat cerebral cortex after permanent middle cerebral artery occlusion.
AB  - Extracellular potassium ion activity ([K+]o) increases precipitously during brain
      ischemia when blood flow falls below threshold values less than approximately 15
      mL/100 g/min. This flow threshold for increase of [K+]o occurs also in focal
      ischemia producing gradient from ischemic core to adjacent normally perfused
      brain. In this study we investigated the spatial and temporal stability of
      extracellular potassium ion and blood flow gradients after permanent middle
      cerebral artery occlusion (MCAO) in rats. [K+]o and regional CBF were measured,
      respectively, with K+-sensitive and polarographic hydrogen-sensitive
      microelectrodes at different cortical locations in the middle cerebral artery
      distribution region. Spatial assessment of [K+]o and regional CBF was conducted
      at 30, 90, and 180 minutes after MCAO. [K+]o in the more lateral cortex (core)
      increased from near 3 mmol/L before MCAO to greater than 50 mmol/L and was
      associated with flow values less than 25% of pre-ischemic levels. Measurements
      medial to the core (penumbra) indicated progressively decreasing levels of [K+]o
      and improvement of CBF. There was a tendency for [K+]o in penumbral zones to
      decrease toward normal levels with time, but there was little dissipation of
      [K+]o in core regions. In contrast, the spatial CBF profile remained remarkably
      constant for the entire recording period. Thus, unlike infarction which has been
      reported to expand with time after focal ischemia, the spatial [K+]o disturbance
      tends to contract primarily due to decreasing [K+]o with time in the penumbra.
      Thus, steady state levels of [K+]o after focal ischemia may not be a valuable
      predictor of cell viability.

PMID- 9778189
TI  - Validation of a less-invasive method for measurement of serotonin synthesis rate
      with alpha-[11C]methyl-tryptophan.
AB  - We tested in normal human subjects a less invasive method to obtain plasma input
      function required in the calculation of the brain serotonin synthesis rate
      measured with positron emission tomography (PET) and alpha-[11C]methyl-tryptophan
      (alpha-MTrp). The synthesis rates derived with the arterial input function were
      compared to those derived from venous plasma and venous sinus time-radioactivity
      curves obtained from dynamic PET images. Dynamic PET images were obtained for the
      lengths up to 90 minutes after an injection of alpha-MTrp (400 to 800 MBq). Input
      functions were generated from both artery and vein in three subjects, and from
      artery only in two subjects. Net unidirectional uptake constants of alpha-MTrp
      (K*; mL/g/min) were calculated in several brain regions graphically using data
      between 20 and 60 minutes after injection with different input functions. In the
      five subjects with arterial sampling, we tested two methods for correcting the
      input functions from the venous samples: (1) normalization to the mean exposure
      time at 20 minutes from arterial curve; and (2) the use of the venous sinus curve
      for the first 20 minutes. Venous curves coincided with the arterial ones after
      about 20 minutes. When the venous curves were used, there was an underestimation
      of the area under the curves up to 20 minutes, resulting in a 5% to 30%
      overestimation of K* values. Combined use of the sinus curve up to 20 minutes and
      venous curve from 20 to 60 minutes as an input function resulted in the K*
      (mL/g/min) values larger by 7.1 +/- 3.8% than the K* values estimated with the
      arterial input function. Normalization of the venous curve to the exposure time
      at 20 minutes obtained from the arterial plasma curve resulted in a bias in the
      K* of about -0.34 +/- 3.32%. The bias from the K* values was propagated to the
      serotonin synthesis rates. The use of a combination of the venous blood samples
      and venous sinus as the input function resulted in an acceptable bias in the
      serotonin synthesis rates from the tissue time-radioactivity curves generated by
      PET.

PMID- 9778190
TI  - Muscarinic cholinergic receptor measurements with [18F]FP-TZTP: control and
      competition studies.
AB  - [18F]Fluoropropyl-TZTP (FP-TZTP) is a subtype-selective muscarinic cholinergic
      ligand with potential suitability for studying Alzheimer's disease. Positron
      emission tomography studies in isofluorane-anesthetized rhesus monkeys were
      performed to assess the in vivo behavior of this radiotracer. First, control
      studies (n = 11) were performed to characterize the tracer kinetics and to choose
      an appropriate model using a metabolite-corrected arterial input function.
      Second, preblocking studies (n = 4) with unlabeled FP-TZTP were used to measure
      nonspecific binding. Third, the sensitivity of [18F]FP-TZTP binding to changes in
      brain acetylcholine (ACh) was assessed by administering physostigmine, an
      acetylcholinesterase (AChE) inhibitor, by intravenous infusion (100 to 200 microg
      x kg(-1) x h(-1)) beginning 30 minutes before tracer injection (n = 7). Tracer
      uptake in the brain was rapid with K1 values of 0.4 to 0.6 mL x min(-1) x mL(-1)
      in gray matter. A model with one tissue compartment was chosen because reliable
      parameter estimates could not be obtained with a more complex model. Volume of
      distribution (V) values, determined from functional images created by pixel-by
      pixel fitting, were very similar in cortical regions, basal ganglia, and
      thalamus, but significantly lower (P < 0.01) in the cerebellum, consistent with
      the distribution of M2 cholinergic receptors. Preblocking studies with unlabeled
      FP-TZTP reduced V by 60% to 70% in cortical and subcortical regions.
      Physostigmine produced a 35% reduction in cortical specific binding (P < 0.05),
      consistent with increased ACh competition. The reduction in basal ganglia (12%)
      was significantly smaller (P < 0.05), consistent with its markedly higher AChE
      activity. These studies indicate that [18F]FP-TZTP should be useful for the in
      vivo measurement of muscarinic receptors with positron emission tomography.

PMID- 9778191
TI  - Cerebral blood flow and cerebrovascular reserve capacity: estimation by dynamic
      magnetic resonance imaging.
AB  - We have developed a new method for estimation of regional CBF (rCBF) and
      cerebrovascular reserve capacity on a pixel-by-pixel basis by means of dynamic
      magnetic resonance imaging (MRI). Thirteen healthy volunteers, 8 patients with
      occlusion and/or high grade stenosis of the internal carotid artery (ICA), and 2
      patients with acute stroke underwent dynamic susceptibility-weighted contrast
      enhanced MRI. Using principles of indicator dilution theory and deconvolution
      analysis, maps of rCBF, regional cerebral blood volume, and of the mean transit
      time (MTT) were calculated. In patients with ICA occlusion/stenosis,
      cerebrovascular reserve capacity was assessed by the rCBF increase after
      acetazolamide stimulation. Mean gray and white matter rCBF values in normals were
      67.1 and 23.7 mL x 100 g(-1) x min(-1), respectively. Before acetazolamide
      stimulation, six of eight patients with ICA occlusions showed decreased rCBF
      values; and in seven patients increased MTT values were observed in tissue
      ipsilateral to the occlusion. After acetazolamide stimulation, decreased
      cerebrovascular reserve capacity was observed in five of eight patients with ICA
      occlusion. In acute stroke, rCBF in the central core of ischemia was less than 8
      mL x 100 g(-1) x min(-1). In peri-infarct tissue, rCBF and MTT were higher than
      in unaffected tissue but rCBF was normal. Dynamic MRI provides important clinical
      information on the hemodynamic state of brain tissue in patients with occlusive
      cerebrovascular disease or acute stroke.

PMID- 9778192
TI  - Collateral inhibition of transcallosal activity facilitates functional brain
      asymmetry.
AB  - The corpus callosum is the largest connection between the functionally asymmetric
      cerebral hemispheres. The objective of this study was to measure functional
      activity of callosal fiber tracts during speech processing. We analyzed the
      regional glucose metabolism of the corpus callosum and of speech-relevant
      cortical areas in 10 normal individuals at rest and during word repetition. We
      used three-dimensionally registered magnetic resonance imaging to visualize the
      individual brain morphology and high-resolution positron emission tomography for
      metabolic measurements. The task-induced metabolic changes of the callosal
      midbody and isthmus had a significant negative correlation with key regions of
      language processing in the left inferior frontal cortex (Brodmann's area 44) and
      in the right superior temporal cortex (Brodmann's area 22) (e.g., correlation of
      metabolic changes in the surface aspects of the right Brodmann's area 22 and the
      callosal midbody/isthmus: r = -0.91, P < 0.001). The study indicates that
      language processing in asymmetrically organized cortical areas inhibits the
      reciprocal transcallosal information exchange in favor of the lateralized mental
      operation. Our data agree with anatomic, electrophysiologic, and pharmacologic
      experiments that point to the important role of collateral inhibition for the
      transcallosal information exchange.

PMID- 9778193
TI  - Deep venous thrombosis: thinking inside out.

PMID- 9778195
TI  - Case of the month: allaying apprehension. Autopsy Committee of the College of
      American Pathologists.

PMID- 9778194
TI  - Establishing the diagnosis of tuberculous pleuritis.

PMID- 9778196
TI  - Suicide, hastening death, and psychiatry.

PMID- 9778197
TI  - Maximizing the cost-effectiveness of lipid-lowering therapy.
AB  - Cardiovascular disease, including coronary heart disease, is the leading cause of
      death both in men and in women in the United States. The purpose of this review
      is to describe the effectiveness of lipid-lowering therapy in reducing
      cardiovascular morbidity and mortality, which has recently been extended to
      patients with mild to moderate hypercholesterolemia, and the cost of providing
      therapy, which would be prohibitive if all persons with hypercholesterolemia
      received treatment. Cost-effectiveness analysis provides a rational means of
      allocating limited health care resources by allowing the comparison of the costs
      of lipid-lowering therapy, in particular, therapy with beta-hydroxy-beta
      methylglutaryl-CoA (coenzyme A) reductase inhibitors (statins), with the costs of
      atherosclerosis that could be prevented by lowering cholesterol. To extend the
      benefits of treatment to the large number of persons not receiving therapy, we
      need to implement more cost-effective treatment by improving risk assessment,
      increasing treatment effectiveness, and reducing the cost of therapy.

PMID- 9778198
TI  - Antimicrobial photosensitive reactions.
AB  - Photosensitivity reactions are recognized as unwanted adverse effects of an array
      of commonly administered topical or systemic medications, including nonsteroidal
      antiinflammatory agents, antifungals, and antimicrobials. When a drug induces
      photosensitivity, exogenous molecules in the skin absorb normally harmless doses
      of visible and UV light, leading to an acute inflammatory response. In phototoxic
      reactions, the damage to tissues is direct; in photoallergic reactions, it is
      immunologically mediated. In vitro and in vivo assay systems can assist in
      predicting or confirming drug photosensitivity. The incidence of photosensitivity
      reactions may be too low to be detected in clinical studies and may become
      recognized only in the postmarketing stage of drug development. Some drugs have
      been withdrawn because of photosensitivity effects that appeared after general
      release. Photosensitivity reactions have been studied for a number of topical
      antimicrobials and for the sulfonamides, griseofulvin, the tetracyclines, and the
      quinolones. Incidence and intensity of drug phototoxicity can vary widely among
      the different compounds of a given class of antimicrobials. When phototoxic
      effects are relatively low in incidence, mild, reversible, and clinically
      manageable, the benefits of an antimicrobial drug may well outweigh the potential
      for adverse photosensitivity effects.

PMID- 9778199
TI  - Assessment of outpatient treatment of deep-vein thrombosis with low-molecular
      weight heparin.
AB  - BACKGROUND: Low-molecular-weight (LMW) heparins are safe and effective for out-of
      hospital treatment of acute deep-vein thrombosis (DVT) in a clinical trial
      setting. We examined the efficacy, safety, and feasibility of home treatment with
      LMW heparin of consecutive eligible patients with acute DVT in a routine care
      setting. In addition, we report our experience with patient compliance,
      acceptance, and satisfaction. METHODS: We performed a prospective cohort study of
      consecutive patients presenting to 2 thromboembolism clinics in a large Ontario
      city. Eligible patients were treated with LMW heparin for a minimum of 5 days and
      with long-term warfarin sodium. Outcomes included the incidences of bleeding and
      recurrence of DVT and pulmonary embolism and patient satisfaction as determined
      by a questionnaire. RESULTS: One hundred thirteen patients with objectively
      confirmed DVT underwent screening; 89 patients were treated at home with LMW
      heparin. During the study, 1 patient died of a combination of pulmonary embolism
      and major bleeding, another patient required admission to the hospital for
      bleeding, and 5 patients with active malignant disease had recurrent DVT. Of the
      patients who completed the satisfaction questionnaire, 75 (91%) of 82 were
      pleased with home treatment; 44 (70%) of 63 felt comfortable self-injecting the
      LMW heparin; and 71 (92%) of 77 were satisfied with the support and instruction
      they received during the outpatient treatment. CONCLUSIONS: Outpatient treatment
      of DVT with LMW heparin is safe, effective, and feasible for most patients and is
      associated with a high degree of patient satisfaction.

PMID- 9778200
TI  - Impact of major cardiovascular disease risk factors, particularly in combination,
      on 22-year mortality in women and men.
AB  - BACKGROUND: The appropriateness of current cardiovascular disease (CVD) risk
      factor guidelines in women continues to be debated. OBJECTIVE: To present new
      data on the appropriateness of current CVD risk factor guidelines, for women and
      men, from long-term follow-up of a large population sample. METHODS:
      Cardiovascular disease risk factor status according to current clinical
      guidelines and long-term impact on mortality were determined in 8686 women and
      10503 men aged 40 to 64 years at baseline from the Chicago Heart Association
      Detection Project in Industry; average follow-up was 22 years. RESULTS: At
      baseline, only 6.6% of women and 4.8% of men had desirable levels for all 3 major
      risk factors (cholesterol level, <5.20 mmol/L [<200 mg/dL]; systolic and
      diastolic blood pressure, <120 and <80 mm Hg, respectively; and nonsmoking). With
      control for age, race, and other risk factors, each major risk factor considered
      separately was associated with increased risk of death for women and men. In
      analyses of combinations of major risk factors, risk increased with number of
      risk factors. Relative risks (RRs) associated with any 2 or all 3 risk factors
      were similar: for coronary heart disease mortality in women, RR= 5.72 (95%
      confidence interval [CI], 2.35-13.93), and in men, RR = 5.51 (95% CI, 3.10-9.77);
      for CVD mortality in women, RR = 4.54 (95% CI, 2.33-8.84), and in men, RR = 4.12
      (95% CI, 2.56-6.37); and for all-cause mortality in women, RR = 2.34 (95% CI,
      1.73-3.15), and in men, RR = 3.20 (95% CI, 2.47-4.14). Absolute excess risks were
      high in women and men with any 2 or all 3 major risk factors. CONCLUSIONS:
      Combinations of major CVD risk factors place women and men at high relative,
      absolute, and absolute excess risk of coronary heart disease, CVD, and all-cause
      mortality. These findings support the value of (1) measurement of major CVD risk
      factors, especially in combination, for assessing long-term mortality risk and
      (2) current advice to match treatment intensity to the level of CVD risk in both
      women and men.

PMID- 9778201
TI  - Tuberculous pleurisy: a study of 254 patients.
AB  - OBJECTIVES: To determine the age at which tuberculous pleural effusions occur,
      the radiological and biochemical characteristics of the effusions, the
      sensitivities of the various diagnostic tests, and the utility of combining
      clinical, radiological, and analytic data in diagnosis. METHODS: We studied the
      case histories of 254 patients in whom tuberculous pleural effusions were
      diagnosed with certainty between January 1, 1989, and June 30, 1997, in a Spanish
      university hospital in a region with a high incidence of tuberculosis. RESULTS:
      The mean (+/-SD) age of the patients was 34.1+/-18.1 years, and 62.2% were
      younger than 35 years. The effusion was on the right side in 55.9% of patients,
      on the left side in 42.5% of patients, and on both sides in 1.6% of patients. In
      81.5% of patients, less than two thirds of the hemithorax was affected.
      Associated pulmonary lesions were detected in 18.9% of patients, of whom 14.6%
      exhibited cavitation. In 93.3% of the effusions, more than 50% of leukocytes were
      lymphocytes, and almost all had the biologic characteristics of exudates (98.8%
      had high total protein contents, 94.9% had high cholesterol levels, and 82.3% had
      high lactate dehydrogenase levels). All but 1 effusion (99.6%) had an adenosine
      deaminase (ADA) concentration higher than 47 U/L, 96.8% (123/127) of the
      effusions had high ADA2 levels, and 89% (73/82) of the effusions had high
      interferon gamma levels. Adenosine deaminase 2 contributed 72.2%+/-12.5% (mean +/
      SD) of total ADA activity. Total ADA activity was significantly correlated with
      ADA2 (r = 0.83) and with interferon gamma (r = 0.30) levels. Definitive diagnosis
      was based on the observation of caseous granulomas in pleural biopsy tissue
      samples in 79.8% of patients, on the results of biopsy cultures in 11.7% of
      patients, and on pleural effusion cultures in the remaining 8.5% of patients.
      Results of the tuberculin skin test were positive in only 66.5% of patients.
      CONCLUSIONS: In these patients, lymphocyte-rich exudative pleural effusions
      occurred, on average, at a young age, with no preference for either the right or
      the left side; normally affected no more than two thirds of the hemithorax; and
      were generally unaccompanied by pulmonary infiltrates. High ADA concentration was
      a highly sensitive diagnostic sign and was caused by a rise in ADA2
      concentration. The most sensitive criterion based on pleural biopsy was the
      observation of caseous granulomas, and culture of biopsy material further
      increased overall sensitivity. Negative skin test results were no guarantee of
      the effusion being nontuberculous. This, together with the low mean age of the
      patients and the low frequency of associated pulmonary lesions, suggests that
      tuberculous pleural effusion is a primary form of tuberculosis in this region.

PMID- 9778202
TI  - Determinants of mortality in elderly patients with heart failure: the role of
      angiotensin-converting enzyme inhibitors.
AB  - BACKGROUND: Despite randomized controlled trials demonstrating mortality
      reduction, many studies have documented persistent low rates of prescription of
      angiotensin-converting enzyme inhibitors (ACE-I) in patients with heart failures;
      the reasons for this pattern remain poorly defined. In addition, some authors
      have argued that the results of carefully controlled clinical trials do not
      translate well into the uncontrolled world of clinical practice, and the
      mortality benefits of ACE-I may not extend into special populations such as the
      elderly. OBJECTIVES: To understand the reasons for failure to prescribe ACE-I to
      Medicare patients with heart failure and to assess the impact of this failure on
      mortality. METHODS: We obtained data by reviewing charts of Medicare patients
      discharged from 7 Colorado hospitals with a diagnosis of heart failure during
      1994. RESULTS: We identified a diagnosis of heart failure in 1016 patients
      without a contraindication to ACE-I. Three hundred seventy-eight of these
      patients were receiving ACE-I at the time of admission. Of the 638 remaining, 257
      had their left ventricular systolic function assessed and 92 had diminished
      function. Of these 92, 50 (54.3%) were discharged on a regimen of ACE-I. The only
      significant difference in baseline comorbidity or demographic variables between
      those given and those not given ACE-I was that patients not prescribed ACE-I were
      older. Using multivariate analysis, younger age and cardiology consultation
      predicted ACE-I prescription (P = .02). By life-table analysis, mortality at 1
      year following discharge from the index hospitalization was lower in those
      treated with ACE-I than in those not so treated (P = .03). The Deyo index of
      comorbidity, prescription of an ACE-I, site of treatment, and presence or absence
      of cardiology consultation were significantly associated with 1-year mortality by
      multivariate analysis (P<.001). CONCLUSIONS: Underinvestigation and
      undertreatment of chronic heart failure persists. Failure to treat elderly
      patients with ACE-I is associated with a mortality that appears to be greater
      than that seen in the placebo arms of large clinical trials of ACE-I therapy.
      Within the population studied, older patients are less likely to be treated.
      Failure of age to significantly add to prediction of mortality implies that the
      apparent bias against treating older patients with chronic heart failure with ACE
      I is not justified. Because mortality is dependent on provider and site of
      treatment, further reductions in mortality from chronic heart failure may require
      intensive and selective local efforts, or development of regional heart failure
      centers.

PMID- 9778203
TI  - Comparison of the efficacy of dihydropyridine calcium channel blockers in African
      American patients with hypertension. ISHIB Investigators Group. International
      Society on Hypertension in Blacks.
AB  - BACKGROUND: Hypertension is a prevalent disease among African Americans, and
      successful treatment rates are low. Since calcium channel blockers are well
      tolerated and efficacious in African Americans, we undertook this study to
      compare the efficacy, safety, and tolerability of 3 commonly prescribed calcium
      channel blockers: amlodipine besylate (Norvasc), nifedipine coat core (CC)
      (Adalat CC), and nifedipine gastrointestinal therapeutic system (GITS) (Procardia
      XL). METHODS: One hundred ninety-two hypertensive patients across 10 study
      centers were randomly assigned to double-blind monotherapy with amlodipine
      besylate (5 mg/d), nifedipine CC (30 mg/d), or nifedipine GITS (30 mg/d) for 8
      weeks. Patients not achieving therapeutic response after 4 weeks had their dose
      doubled for the next 4 weeks. The primary end point was a comparison of the
      average reduction (week 8 minus baseline) in 24-hour ambulatory diastolic blood
      pressure (DBP). Secondary end points included a comparison of average 24-hour
      ambulatory systolic blood pressure (SBP), office SBP or DBP reduction, responder
      rates, safety, and tolerability. RESULTS: One hundred sixty-three patients were
      evaluable for efficacy after 8 weeks. There was no significant difference in the
      average 24-hour ambulatory DBP (-8.5, -9.0, and -6.1 mm Hg, respectively) or SBP
      (-14.3, -15.7, and -11.8 mm Hg, respectively) reduction. Average office SBP and
      DBP were reduced to a comparable degree (19-22 mm Hg [P =.50] and 12-14 mm Hg [P
      =.51], respectively). Responder rates (DBP <90 or reduced by > or = 10 mm Hg)
      were similar (P = .38). Discontinuation rates and adverse event frequency were
      distributed similarly across the 3 treatment groups. CONCLUSION: The efficacy,
      safety, and tolerability of the 3 dihydropyridine calcium channel blockers are
      equivalent in African Americans with stages 1 and 2 hypertension.

PMID- 9778204
TI  - A randomized trial of nortriptyline for smoking cessation.
AB  - BACKGROUND: Smoking cessation rates with current therapy are suboptimal. One
      class of drugs that may improve cessation is the tricyclics. OBJECTIVE: To add
      nortriptyline hydrochloride to a behavioral smoking cessation program to enhance
      cessation rates and reduce withdrawal symptoms. SUBJECTS AND METHODS: We
      conducted a randomized, double-blind, placebo-controlled trial at an affiliated
      Department of Veterans Affairs Medical Center and an Army Medical Center.
      Subjects were aged 18 through 70 years, smoked 10 or more cigarettes per day, and
      were without current major depression. Nortriptyline hydrochloride or matched
      placebo was started at 25 mg before bed 10 days prior to quit day and titrated to
      75 mg/d or to the maximal tolerated dose. The behavioral intervention consisted
      of 2 group sessions and 12 individual follow-up visits. Withdrawal symptoms were
      measured using a daily diary, and smoking cessation was defined as self-reported
      abstinence, expired carbon monoxide of 9 ppm or less, and a 6-month urine
      cotinine level of less than 50 ng/mL. RESULTS: A total of 214 patients were
      randomized (108 to nortriptyline and 106 to placebo). There was a significant
      reduction in several withdrawal symptoms including anxious/tense,
      anger/irritability, difficulty concentrating, restlessness, and impatience by day
      8 after quit day in the nortriptyline group. The cessation rate at 6 months was
      15 (14%) of 108 and 3 (3%) of 106, respectively (P = .003; absolute difference,
      11%; 95% confidence interval, -18% to -4%). Nortriptyline caused frequent adverse
      effects, including dry mouth (64%) and dysgeusia (20%). CONCLUSIONS: We conclude
      that nortriptyline led to an increased short-term cessation rate compared with
      placebo. In addition, there were significant, but relatively small, reductions in
      withdrawal symptoms. Nortriptyline may represent a new therapeutic approach to
      smoking cessation.

PMID- 9778205
TI  - Influence of human immunodeficiency virus 1 infection and degree of
      immunosuppression in the clinical characteristics and outcome of infective
      endocarditis in intravenous drug users.
AB  - BACKGROUND: Immunosuppression caused by human immunodeficiency virus 1 (HIV)
      infection appears to modify the clinical characteristics and to increase the
      severity of several bacterial infections. The impact of HIV infection and the
      degree of immunosuppression on the clinical characteristics and outcome of
      infective endocarditis (IE) in intravenous (IV) drug users has not been well
      characterized. METHODS: Prospective cohort study among 292 consecutive IV drug
      users with IE diagnosed in 2 academic institutional hospitals in Barcelona,
      Spain, from January 1, 1984, to October 31, 1995. Serostatus of HIV infection was
      documented in 283 patients. We measured demographics, clinical and biological
      data, cause, echocardiographic findings, HIV serostatus and classification, CD4
      cell count, complications, and mortality. RESULTS: Among the 283 episodes of IE,
      216 (76.3%) were in HIV-infected patients and 67 (23.7%) in non-HIV-infected
      patients. Rate of IE per 1000 admissions ranged from 0.17 to 0.82 per year,
      peaking in 1989. Characteristics of IE independently associated with HIV
      infection were right-side involvement (odds ratio [OR], 7.6; 95% confidence
      interval [CI], 3.5-16.7), a micro-organism different from viridans streptococci
      (OR, 2.5; 95% CI, 1.1-5.9), duration of drug abuse longer than 5 years (OR, 5.0;
      95% CI, 2.4-10.3), and white blood cell count of no more than 10 X 10(9)/L (OR,
      2.2; 95% CI, 1.1-4.2). There were no significant differences in mortality due to
      IE according to HIV serostatus. Among the 216 patients with HIV infection, the
      variables independently associated with worse outcome were CD4 cell count lower
      than 0.200 x 10(9)/L and left-sided or mixed IE. CONCLUSIONS: Although there is a
      difference in clinical presentation in IE in IV drug users, outcome was similar
      according to their HIV status. However, among HIV-infected patients, severe
      immunosuppression and mixed or left-side valvular involvement were strong risk
      factors for mortality.

PMID- 9778206
TI  - Sex differences in mortality after myocardial infarction: evidence for a sex-age
      interaction.
AB  - BACKGROUND: Studies of sex differences in mortality after myocardial infarction
      (MI) have shown conflicting results. OBJECTIVES: To test the hypothesis that sex
      differences in mortality after MI vary according to patients' age, with younger
      women, but not older women, having a higher mortality compared with men. METHODS:
      We performed a retrospective cohort study of 1025 consecutive patients who met
      accepted criteria for MI in 1992 and 1993 in 15 Connecticut hospitals. Data for
      the study were abstracted from medical records. RESULTS: Women had a 40% higher
      hospital mortality rate than men. Simple age adjustment eliminated the sex
      difference in mortality rate (odds ratio, 0.99; 95% confidence interval, 0.66
      1.48). However, when the sample was subdivided into 2 age groups, women younger
      than 75 years showed twice as high a mortality rate as men in the same age group,
      while among older patients no difference in mortality was found. In multivariate
      analyses the interaction of sex with age was highly significant, even after
      adjusting for comorbid conditions, clinical severity, process of care, and
      hospital characteristics. In the fully adjusted model, this interaction indicated
      that among patients younger than 75 years women had 49% higher odds of hospital
      death than men, while in the age group 75 years or older women had 46% lower odds
      of death compared with men. CONCLUSIONS: A higher mortality of women compared
      with men after MI is confined to the younger age groups. The sex-age interaction
      should be considered when examining sex differences in mortality after MI.

PMID- 9778208
TI  - Liver failure and peripheral facial paralysis in a case of primary amyloidosis.

PMID- 9778207
TI  - Angioneurotic edema attributed to the use of losartan.
AB  - BACKGROUND: Angioedema is a well-known adverse effect of angiotensin-converting
      enzyme inhibitors. The bradykinin accumulation as a result of the decreased
      degradation of bradykinin is thought to be the causal mechanism. Angiotensin II
      antagonists seem to have no effect on the degradation of bradykinin. Therefore,
      it was expected that angioedema would not occur during treatment with losartan
      potassium, the first orally active angiotensin II antagonist. METHODS: We
      reviewed the 13 case reports of angioedema associated with the use of losartan
      reported to Lareb (Netherlands Pharmacovigilance Foundation, Den Bosch) and to
      the Drug Safety Unit of the Inspectorate for Health Care, Ryswyh, in the
      Netherlands since the introduction of losartan in 1995 until May 1997. RESULTS:
      In all 13 cases, a diagnosis of angioedema attributed to the use of losartan
      seems to be very plausible. In 7 cases the diagnosis could not be confirmed by a
      physician because the symptoms had already been resolved, but the signs and
      symptoms clearly indicated angioedema. The adverse reactions occurred within 24
      hours to 16 months after the initiation of losartan therapy. Three patients had
      previously experienced angioedema during treatment with an angiotensin-converting
      enzyme inhibitor. Eleven of the patients involved were women and 2 were men.
      CONCLUSIONS: Our observations strongly suggest that the onset of angioedema was
      associated with the use of losartan. Physicians and pharmacists should be aware
      of this potentially life-threatening complication. It may be advisable not to
      prescribe angiotensin II antagonists to patients with a history of angioedema (of
      whatever origin).

PMID- 9778209
TI  - Managed care: our self-inflicted illness and how to eradicate it.

PMID- 9778210
TI  - The transition to managed care has to be seen as at least bittersweet.

PMID- 9778211
TI  - ACR presidential address: Rheum for more. American College of Rheumatology.

PMID- 9778212
TI  - Hormonal, environmental, and infectious risk factors for developing systemic
      lupus erythematosus.

PMID- 9778213
TI  - Oklahoma Choctaw and systemic sclerosis: the founder effect and genetic
      susceptibility.

PMID- 9778214
TI  - Association of microsatellite markers near the fibrillin 1 gene on human
      chromosome 15q with scleroderma in a Native American population.
AB  - OBJECTIVE: To localize disease genes for scleroderma, or systemic sclerosis
      (SSc), in a population of Choctaw Native Americans with a high prevalence of SSc,
      in which there is evidence of a possible founder effect. METHODS: A candidate
      gene approach was used in which microsatellite alleles on human chromosomes 15q
      and 2q, homologous to the murine tight skin 1 (tsk1) and tsk2 loci, respectively,
      were analyzed in Choctaw SSc cases and race-matched normal controls for possible
      disease association. Genotyping first-degree relatives of the cases identified
      potential disease haplotypes, and haplotype frequencies were obtained by
      expectation-maximization and maximum-likelihood estimation methods.
      Simultaneously, the ancestral origins of contemporary Choctaw SSc cases were
      ascertained using census and historical records. RESULTS: A multilocus 2-cM
      haplotype was identified on human chromosome 15q homologous to the murine tsk1
      region, which showed a significantly increased frequency in SSc cases compared
      with controls. This haplotype contains 2 intragenic markers for the fibrillin 1
      (FBN1) gene. Genealogical studies demonstrated that the SSc cases were distantly
      related, and their ancestry could be traced back to 5 founding families in the
      mid-eighteenth century. The probability that the SSc cases share this haplotype
      due to familial aggregation effects alone was calculated and found to be very
      low. There was no evidence of any microsatellite allele disturbances on
      chromosome 2q in the region homologous to the tsk2 locus or the region containing
      the interleukin-1 family. CONCLUSION: A 2-cM haplotype on chromosome 15q that
      contains FBN1 is associated with scleroderma in Choctaw Native Americans from
      Oklahoma. This haplotype may have been inherited from common founders about 10
      generations ago and may contribute to the high prevalence of SSc that is now
      seen.

PMID- 9778215
TI  - Anti-endothelial cell antibody binding makes negatively charged phospholipids
      accessible to antiphospholipid antibodies.
AB  - OBJECTIVE: Anti-endothelial cell autoantibodies (AECA) are often associated with
      antibodies to anionic phospholipids (PL), such as phosphatidylserine (PS). Yet,
      beta2-glycoprotein I (beta2GPI)-dependent anti-PL antibodies (aPL) do not have
      access to their target antigens on the membrane of endothelial cells (EC). Given
      that AECA are capable of exposing PS and, thereby, initiating apoptosis, we
      explored the relationships between AECA, beta2GPI, and aPL on the surface of EC.
      METHODS: Human EC were incubated with mouse AECA monoclonal antibodies, and the
      translocation of PS was established through the binding of annexin V, which binds
      specifically to PS. A rabbit anti-beta2GPI antibody and biotin-conjugated F(ab')2
      aPL derived from 3 patients were also used to detect beta2GPI on the cells.
      RESULTS: Twenty percent to 36% of the cells expressed anionic PL following
      incubation with AECA, as revealed by the binding of annexin V and beta2GPI. The
      proportion of anionic PL-expressing EC (up to 90%) correlated with the period of
      incubation of EC with AECA and depended on the dose of AECA. Bound aPL resided
      exclusively within the AECA-positive EC population. CONCLUSION: Based on our
      findings, AECA may be pathogenic. Some of them may even have the potential to
      induce production of aPL.

PMID- 9778216
TI  - Imbalance between interstitial collagenase and tissue inhibitor of
      metalloproteinases 1 in synoviocytes and fibroblasts upon direct contact with
      stimulated T lymphocytes: involvement of membrane-associated cytokines.
AB  - OBJECTIVE: To determine whether direct cell-cell contact with stimulated T
      lymphocytes (a) differentially modulates the production of interstitial
      collagenase (matrix metalloproteinase 1 [MMP-1]) and tissue inhibitor of
      metalloproteinases 1 (TIMP-1) on human synoviocytes and dermal fibroblasts, and
      (b) induces the production of prostaglandin E2 (PGE2); and to identify the
      membrane-associated factors on T cell surfaces involved in these mechanisms.
      METHODS: Dermal fibroblasts and fibroblast-like synovial cells (synoviocytes)
      were cultured with fixed T cells, isolated plasma membranes from T cells,
      interleukin-1beta (IL-1beta; 250 pg/ml), or transforming growth factor beta
      (TGFbeta; 5 ng/ml). Culture supernatants were assayed for the production of MMP
      1, TIMP-1, and PGE2. The expression of MMP-1 and TIMP-1 messenger RNA was
      analyzed by Northern blot of total fibroblast RNA. RESULTS: Membranes of
      stimulated T cells, i.e., human peripheral blood T lymphocytes (PBTL) and the
      human T cell line HUT-78, induced the production of PGE2 and MMP-1 on both
      synoviocytes and dermal fibroblasts. TIMP-1 production was enhanced upon contact
      with PBTL stimulated for short periods of time (2-4 hours) but not for longer
      periods. Similar results were obtained with CD4+ and CD8+ synovial tissue T cell
      clones (TCCs), which induced the production of TIMP-1 by fibroblasts when
      stimulated for short (2-4 hours), but not long, periods of time. This time
      dependency was not observed with HUT-78 cells. The production of MMP-1 by
      fibroblasts and synoviocytes upon cellular contact with stimulated T cells was
      higher than that induced by an optimum concentration of IL-1beta, whereas the
      production of PGE2 was equivalent or slightly lower. Cell membrane-associated IL
      1alpha and tumor necrosis factor a, but not CD69, CD40 ligand, or CD11b, were
      involved in the induction of MMP-1 and PGE2 production, as shown by blockade
      experiments using monoclonal antibodies and cytokine antagonists. CONCLUSION:
      Synovial tissue TCCs and PBTL stimulated for long periods of time trigger the
      production of PGE2 and MMP-1, but not TIMP-1, in synoviocytes and dermal
      fibroblasts, thus inducing an imbalance between the metalloenzyme and its
      inhibitor. These results demonstrate that T cells may affect fibroblast and
      synoviocyte functions directly (i.e., by contact activation) and indirectly
      (i.e., by activation of cytokine production in monocyte/macrophages, which in
      turn, trigger stromal cell functions). Since the production of MMPs in
      monocyte/macrophages is also induced upon contact with stimulated T cells, our
      results strongly suggest that contact of synovial cells with chronically
      stimulated T lymphocytes favors matrix catabolism. By analogy, this mechanism may
      trigger tissue destruction in vivo and, thus, may potentiate tissue destruction
      in chronic inflammatory diseases such as RA.

PMID- 9778217
TI  - The role of oncostatin M in animal and human connective tissue collagen turnover
      and its localization within the rheumatoid joint.
AB  - OBJECTIVE: To study the interaction of interleukin-1alpha (IL-1alpha) and
      oncostatin M (OSM) in promoting cartilage collagen destruction. METHODS: Bovine,
      porcine, and human cartilage and human chondrocytes were studied in culture. The
      levels of collagenase (matrix metalloproteinase 1 [MMP-1]) and tissue inhibitor
      of metalloproteinases 1 (TIMP-1) were measured by bioassay and enzyme-linked
      immunosorbent assay (ELISA). The levels of OSM in rheumatoid synovial fluid were
      measured by ELISA. RESULTS: When combined with OSM, IL-1alpha, IL-1beta, and
      tumor necrosis factor alpha released proteoglycan and collagen from cartilage.
      OSM was the only member of the IL-6 family to have this effect. Human tendon also
      responded to IL-1alpha and OSM. OSM increased the production of MMP-1 and TIMP-1
      but when combined with IL-1alpha, synergistically promoted MMP-1 production in
      human chondrocytes and synovial fibroblasts. High levels of OSM were found in
      human rheumatoid synovial fluids, and confocal microscopy showed that OSM was
      produced by macrophages in rheumatoid synovial tissue. CONCLUSION: These results
      highlight an important new mechanism by which there is irreversible loss of
      collagen from cartilage.

PMID- 9778218
TI  - HPRT- mutant T cells in the peripheral blood and synovial tissue of patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the frequency and characteristics of hprt- mutant T
      lymphocytes in the peripheral blood and synovium of rheumatoid arthritis (RA)
      patients compared with controls, and to correlate these findings with disease
      parameters. METHODS: An hprt- T cell assay was performed on blood and synovial
      samples from 93 RA patients, 8 osteoarthritis (OA) patients, and 19 control
      subjects. T cell clones were studied by flow cytometry and evaluated for
      fibronectin adhesion. RESULTS: RA patients showed a 5-fold increase in the
      frequency of mutant T cells in the peripheral blood compared with that in control
      peripheral blood, and a further 10-fold increase in the mutant T cell frequency
      in synovial tissue. In OA patients, the synovium also had a significantly higher
      frequency of hprt- mutant T cells compared with the peripheral blood, but at a
      lower level than in the rheumatoid synovium. RA peripheral blood mutant T cell
      clones displayed elevated fibronectin adhesion and beta1 integrin expression,
      similar to that observed in the RA synovial T cell lines. CONCLUSION: The origin
      of the mutated T cells in the peripheral blood of these patients appears to be
      the inflamed synovium of RA, and to a lesser extent, of OA, where the cells are
      exposed to a mitogenic and genotoxic environment.

PMID- 9778219
TI  - Pathogenic mechanisms in the rheumatoid nodule: comparison of proinflammatory
      cytokine production and cell adhesion molecule expression in rheumatoid nodules
      and synovial membranes from the same patient.
AB  - OBJECTIVE: To investigate the production of proinflammatory cytokines and
      expression of cell adhesion molecules in the rheumatoid nodule. METHODS: Cytokine
      content (tumor necrosis factor alpha [TNFalpha], interleukin-1beta [IL-1beta],
      and IL-1 receptor antagonist [IL-1Ra]), at the messenger RNA (mRNA) and protein
      levels, and cell adhesion molecule expression were studied in 16 rheumatoid
      nodules and 6 synovial membranes. RESULTS: Macrophages in the rheumatoid nodules
      contained TNFalpha, IL-1beta, and IL-1Ra mRNA and protein, particularly in
      perivascular cells of the stroma and in the palisading layer. All cell adhesion
      molecules studied were expressed in both the rheumatoid nodules and synovial
      membranes, with increased expression of E-selectin in the rheumatoid nodule
      compared with the synovial membrane, and with the absence of vascular cell
      adhesion molecule 1 expression on cells of the palisading layer in the rheumatoid
      nodule. CONCLUSION: The presence of similar proinflammatory cytokines and cell
      adhesion molecules in the rheumatoid nodule and synovial membrane suggests that
      similar pathogenic processes result in the chronic inflammation and tissue
      destruction in these lesions.

PMID- 9778221
TI  - Therapeutic actions of cyclosporine and anti-tumor necrosis factor alpha in
      collagen-induced arthritis and the effect of combination therapy.
AB  - OBJECTIVE: To define the mechanisms of action of 2 novel drugs, cyclosporine and
      anti-tumor necrosis factor alpha (TNFalpha), in collagen-induced arthritis and to
      determine the effect of combination therapy. METHODS: Type II collagen-immunized
      DBA/1 mice with established arthritis were treated with cyclosporine alone, anti
      TNFalpha alone, cyclosporine plus anti-TNFalpha, or saline. RESULTS: Cyclosporine
      was found to ameliorate arthritis, suppress interferon-gamma (IFNgamma)
      production by CD4+ T cells, and reduce TNFalpha expression in arthritic joints.
      However, cyclosporine did not directly inhibit TNFalpha production by
      macrophages, indicating that the decrease in TNFalpha expression observed in vivo
      was probably an indirect consequence of the reduction in type 1 T helper cell
      activity. Anti-TNFalpha also reduced IFNgamma production by T cells, indicating
      that TNFalpha is involved in the cellular immune response to collagen. Combined
      treatment with cyclosporine plus anti-TNFalpha had an additive therapeutic
      effect. CONCLUSION: Although cyclosporine and anti-TNFalpha target different
      points in the inflammatory pathway, there is an overlap in the consequences of
      their actions in vivo.

PMID- 9778220
TI  - Altered susceptibility to collagen-induced arthritis in transgenic mice with
      aberrant expression of interleukin-1 receptor antagonist.
AB  - OBJECTIVE: To determine the effect of overexpression or deletion of interleukin-1
      receptor antagonist (IL-1Ra) in collagen-induced arthritis (CIA). METHODS: Mice
      overexpressing the IL-1Ra gene under the control of its endogenous promoter, mice
      lacking IL-1Ra, and normal littermate controls were immunized with bovine type II
      collagen (CII) and compared in terms of features of CIA. RESULTS: Mice
      overexpressing IL-1Ra had a significant reduction in the incidence and severity
      of CIA. After CII immunization, IL-1Ra messenger RNA was overexpressed in the
      spleens, but not in the paws, of transgenic mice. Minimal differences were
      observed in the humoral or cellular immune responses to CII. Mice lacking IL-1Ra
      had a significantly earlier onset of CIA, with increased severity. CONCLUSION:
      Endogenous expression of IL-1Ra is a critical determinant of susceptibility to
      CIA. These findings suggest potential therapeutic interventions for autoimmune
      arthritis.

PMID- 9778222
TI  - The Fc gammaRIIIA-158F allele is a risk factor for systemic lupus erythematosus.
AB  - OBJECTIVE: To study whether the Fc gammaRIIIA-158V/F polymorphism, which affects
      IgG binding affinity, is a risk factor for systemic lupus erythematosus (SLE).
      METHODS: We genotyped a group of 70 Caucasian SLE patients for all known Fc
      gammaR polymorphisms. Of this group, 45 patients (64%) had nephritis. In 35
      patients, this diagnosis was confirmed by renal biopsy. RESULTS: In the total
      group of 70 SLE patients, the frequency of the Fc gammaRIIIA-158F allele was
      0.74, versus 0.57 in healthy controls (P = 0.003). The genotype distribution of
      the Fc gammaRIIIA-158V/F polymorphism was also significantly different from that
      of the control population (P = 0.004). The distribution of the other Fc gammaR
      polymorphisms--Fc gammaRIIA-131R/H, Fc gammaRIIIB-NA(1,2), and Fc gammaRIIIA
      48L/R/H--was similar in SLE patients and controls. CONCLUSION: In our group of
      SLE patients, only the distribution of the alleles of the Fc gammaRIIIA-158V/F
      polymorphism was significantly different from that in the control group. This
      might indicate that macrophage expression of the Fc gammaRIIIA-158F isoform is
      involved in the disturbed clearance of immune complexes in patients with SLE.

PMID- 9778223
TI  - Differential roles of the anti-ribosomal P antibody and antineuronal antibody in
      the pathogenesis of central nervous system involvement in systemic lupus
      erythematosus.
AB  - OBJECTIVE: To compare the role of antibodies against the ribosomal P protein
      (anti-P) with that of antibodies against neuronal cells (anti-N) in the
      pathogenesis of central nervous system (CNS) involvement in systemic lupus
      erythematosus (SLE). METHODS: Sera from 87 SLE patients (27 with non-CNS SLE, 34
      with lupus psychosis, and 26 with nonpsychotic CNS lupus) and from 20 control
      patients with neurologic manifestations without SLE and cerebrospinal fluid (CSF)
      from 41 patients with CNS lupus and from the 20 control patients were assayed for
      IgG anti-P and anti-N by an enzyme-linked immunosorbent assay (ELISA) using
      ribosomal P synthetic peptides and by a cell ELISA using paraformaldehyde-fixed
      SK-N-MC neuroblastoma cell lines, respectively. RESULTS: Serum anti-P levels were
      significantly elevated in patients with lupus psychosis compared with those with
      non-CNS SLE or those with nonpsychotic CNS lupus, whereas there were no
      significant differences in serum anti-N levels among these 3 groups. In contrast,
      CSF anti-N levels were significantly elevated in patients with lupus psychosis
      compared with those with nonpsychotic CNS lupus and compared with non-SLE
      controls, whereas CSF anti-P were not detected in most of the patients.
      CONCLUSION: The results indicate that anti-P in the systemic circulation and anti
      N in the CSF are involved in the development of lupus psychosis.

PMID- 9778224
TI  - Antigen-specific antibody responses in lupus patients following immunization.
AB  - OBJECTIVE: To determine the safety and efficacy of 3 clinically relevant vaccines
      in patients with systemic lupus erythematosus (SLE). METHODS: We studied 73
      consecutive SLE patients immunized with pneumococcal, tetanus toxoid (TT), and
      Haemophilus influenzae type B (HIB) vaccines. Patients were evaluated
      preimmunization and 12 weeks postimmunization for disease activity and
      immunization side effects. RESULTS: Eighty-four percent of the SLE patients
      developed a 4-fold titer increase in response to at least 1 vaccine, with 51%
      developing a 2-fold titer increase with all 3 vaccines. The majority of SLE
      patients developed protective levels of antibody to TT (90%) and HIB (88%).
      Although protective antibody levels could not be determined for pneumococcus,
      almost half of the patients (47%) developed a 4-fold antibody response. There was
      a trend toward a lower antibody response in patients with active disease treated
      with immunosuppressive therapy. Overall lupus disease activity was unaffected by
      immunization. CONCLUSION: Immunization is safe in SLE patients, with the
      overwhelming majority developing protective antibody levels. Therefore, SLE
      patients should receive immunizations according to the recommendations of the
      Centers for Disease Control and Prevention and the Immunization Practices
      Advisory Committee.

PMID- 9778225
TI  - Intravenous pulse administration of cyclophosphamide versus daily oral treatment
      in patients with antineutrophil cytoplasmic antibody-associated vasculitis and
      renal involvement: a prospective, randomized study.
AB  - OBJECTIVE: There is growing concern about the toxic side effects of daily oral
      cyclophosphamide (CYC) treatment. Intravenous (i.v.) pulse administration of CYC
      has been shown to be effective in patients with systemic lupus erythematosus, but
      contradictory results have been reported in patients with antineutrophil
      cytoplasmic antibody (ANCA)-associated vasculitis. METHODS: The efficacy and
      toxicity of i.v. pulse administration of CYC (0.75 gm/m2) versus daily oral CYC
      treatment (2 mg/kg body weight) were investigated in a prospective, randomized,
      multicenter study in patients with ANCA-associated vasculitis and renal
      involvement. RESULTS: The cumulative CYC dose was reduced by 57% in patients with
      i.v. pulse treatment (n = 22) compared with patients treated with daily oral
      therapy (n = 25). Patient survival, remission rate, time of remission, relapse
      rate, and outcome of renal function were not different between the 2 treatment
      groups. However, the rate of leukopenia (P < 0.01) and severe infections (P <
      0.05 by 1-tailed test) was significantly reduced in the i.v. pulse group compared
      with the group receiving daily oral treatment. Moreover, gonadal toxicity was
      reduced in the i.v. pulse group, as indicated by significantly lower levels of
      follicle-stimulating hormone. CONCLUSION: This randomized study shows that i.v.
      CYC administration is an effective therapeutic tool with low toxicity in patients
      with ANCA-associated vasculitis and renal involvement.

PMID- 9778226
TI  - Validation of rheumatoid arthritis improvement criteria that include simplified
      joint counts.
AB  - OBJECTIVE: To study the validity of response criteria for rheumatoid arthritis
      (RA) that included 28-joint counts instead of more comprehensive joint counts.
      METHODS: In a double-blind, placebo-controlled trial of 105 patients treated with
      methotrexate, sulfasalazine, or both, response was evaluated at week 52. Both
      European League Against Rheumatism and American College of Rheumatology
      definitions of response, with comprehensive as well as simplified joint counts,
      were calculated. We studied the differences between the criteria with and without
      simplified joint counts, the discriminating capacity between treatment groups,
      and the association with change in functional capacity and joint damage. RESULTS:
      Response criteria that included 28-joint counts classified patients' responses
      more conservatively. No differences between treatment groups were found with
      either set of response criteria. The association with change in functional
      capacity was significant in all cases. All response criteria were significantly
      associated with radiographic progression of RA. CONCLUSION: Improvement criteria
      that include 28-joint counts are as valid as the original improvement criteria
      that included more comprehensive joint counts.

PMID- 9778227
TI  - Depression and the long-term risk of pain, fatigue, and disability in patients
      with rheumatoid arthritis.
AB  - OBJECTIVE: To determine whether a previous episode of major depression leaves a
      "scar" that places previously depressed patients with rheumatoid arthritis (RA)
      at risk for experiencing high levels of pain, fatigue, and disability. METHODS: A
      cohort of 203 patients with RA was randomly selected from a national panel and
      interviewed by phone about pain, fatigue, depressive symptoms, disability, and
      history of major depression. RESULTS: Excluding patients who met the criteria for
      current major depression, patients with both a history of depression and many
      depressive symptoms at the time of the interview (dysphoria) reported more pain
      than those without current dysphoria, irrespective of whether they had a history
      of depression. Dysphoria alone was not reliably related to pain reports.
      CONCLUSION: An episode of major depression, even if it occurs prior to the onset
      of RA, leaves patients at risk for higher levels of pain when depressive symptoms
      persist, even years after the depressive episode.

PMID- 9778228
TI  - Reduced thiopurine methyltransferase activity and development of side effects of
      azathioprine treatment in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To investigate thiopurine enzyme activities for their possible value
      in predicting the development of azathioprine (AZA)-related toxicity in patients
      with rheumatoid arthritis (RA). METHODS: Patients with longstanding RA (n = 33)
      were enrolled in a study of treatment with AZA. Before the initiation of AZA
      treatment and at months 1 and 6 of treatment, we measured activities of the
      purine key enzymes hypoxanthine guanine phosphoribosyltransferase, 5'
      nucleotidase, purine nucleoside phosphorylase, and thiopurine methyltransferase
      (TPMT). Controls included patients with early RA (n = 24) and healthy volunteers
      (n = 42). RESULTS: Fourteen of the 33 patients rapidly developed severe side
      effects, most frequently gastrointestinal (GI) intolerance. Compared with the
      other groups, the group with adverse effects had significantly lower TPMT
      activities (P = 0.004). Seven of 8 patients with reduced ("intermediate")
      baseline TPMT levels developed toxicity, resulting in a significant relationship
      (P = 0.005) between toxicity and "intermediate" TPMT activity. Compared with
      "high" activity, baseline intermediate TPMT activity gave a relative risk of 3.1
      (95% confidence interval 1.6-6.2) for the development of severe toxicity with AZA
      treatment. CONCLUSION: In RA patients, inherited intermediate TPMT activity seems
      predictive for the development of severe side effects of AZA. Clinicians should
      consider measuring TPMT prior to treatment initiation to improve the safety of
      AZA use. We hypothesize that GI intolerance may also be related to a thiopurine
      metabolic imbalance.

PMID- 9778229
TI  - Estrogen replacement therapy and worsening of radiographic knee osteoarthritis:
      the Framingham Study.
AB  - OBJECTIVE: To examine whether estrogen replacement therapy (ERT) prevents
      worsening of radiographic knee osteoarthritis (OA) in elderly women. METHODS: A
      total of 551 women ages 63-91 years (mean age 71) in the Framingham Study were
      followed up from biennial examination 18 (1983-1985) to examination 22 (1992
      1993). Data on postmenopausal ERT were obtained every 2 years. Subjects were
      classified into 3 groups according to their estrogen use at biennial examination
      18: never users (n = 349), past users (n = 162), and current users (n = 40).
      Women received anteroposterior weight-bearing knee radiographs at examinations 18
      and 22. Using the Kellgren and Lawrence criteria, global radiographic knee OA was
      assessed, (grade range 0-4) and individual radiographic features, such as
      osteophytes and joint space narrowing, were scored from 0 to 3. Worsening was
      defined as either development of radiographic OA that was not present at baseline
      (incident OA) or progression of baseline radiographic OA by > or =1 Kellgren and
      Lawrence grade (progressive OA). Potential confounding factors included age, body
      mass index, weight change, smoking, knee injury, physical activity level, and
      bone mineral density at the femoral neck. RESULTS: During 8 years of followup,
      17.4% of knee radiographic scores worsened by 1 grade and 5.8% by 2 or 3 grades
      among never users of ERT. Among current estrogen users, only 11.7% of knee
      radiographic scores worsened by 1 grade and none worsened by more than 1 grade.
      After adjusting for age and other potential confounding factors, the relative
      risk of incident radiographic knee OA in comparison with never users of estrogen
      was 0.8 (95% confidence interval [95% CI] 0.5-1.4) in past users and 0.4 (95% CI
      0.1-3.0) in current users. Current use of estrogen also showed a trend toward
      decreased risk of progressive knee OA compared with never use (odds ratio [OR]
      0.5, 95% CI 0.1-2.9). When both incident and progressive radiographic knee OA
      cases were combined, current ERT use had a 60% decreased risk compared with never
      use (OR 0.4, 95% CI 0.1-1.5). CONCLUSION: This is the first prospective cohort
      study to examine the effects of ERT on radiographic knee OA. The results indicate
      that current use of ERT had a moderate, but not statistically significant,
      protective effect against worsening of radiographic knee OA among elderly white
      women. These findings corroborate those of cross-sectional studies and point
      further to a potential benefit of female hormones in OA.

PMID- 9778230
TI  - Manometry of the upper intestinal tract in patients with systemic sclerosis: a
      prospective study.
AB  - OBJECTIVE: To assess both the prevalence and the characteristics of motor
      disorders of the small bowel in patients with systemic sclerosis (SSc) and to
      investigate for an association between clinical manifestations in the upper
      intestinal tract, capillaroscopic features, esophageal motor impairment, and
      manometric evidence of motor disturbances. METHODS: Fasting and postprandial
      motor activity of the upper intestinal tract was studied in 17 consecutive
      patients with SSc (6 with and 11 without clinical manifestations of small bowel
      involvement) and 17 age- and sex-matched healthy control subjects. RESULTS: The
      prevalence of manometric evidence of intestinal involvement was as high as 88% in
      the SSc patients; normal motor activity was present in only 2 patients. The
      median values for duodenal and jejunal interdigestive phase III migrating motor
      complex duration, amplitude, and velocity and the postprandial motility index
      were therefore lower in SSc patients compared with controls. Our manometric
      findings indicated that there are both neuropathic and myopathic stages of upper
      intestinal tract dysfunction in SSc. Furthermore, no association could be found
      between the severity of the intestinal manometric abnormalities and clinical
      presentation, SSc subsets, disease score, capillaroscopic findings, or esophageal
      manometric impairment. CONCLUSION: We suggest that manometry of the upper
      intestinal tract may be useful in SSc patients with clinical manifestations in
      the small bowel (i.e., malabsorption syndrome or pseudoobstruction) in that it
      can be used to accurately evaluate both the nature and the severity of motor
      disturbances. Furthermore, this procedure can be used to assist in the selection
      of patients who may require octreotide therapy.

PMID- 9778231
TI  - Poncet's disease and papulonecrotic tuberculid in a patient infected with the
      human immunodeficiency virus.
AB  - We report the case of a 27-year-old patient with the human immunodeficiency virus
      (HIV) infection who presented with a 2-week history of crops of painful, red
      papules over the trunk and extremities, together with a sterile, symmetric
      polyarthritis involving the small and large joints. Histologic study of a skin
      biopsy specimen demonstrated features of papulonecrotic tuberculid. Analytical
      and microbiologic studies ruled out tuberculous infection. Both the synovial and
      the skin processes were considered to be an immune response secondary to
      Mycobacterium tuberculosis infection. Specific treatment was established, and
      there was marked improvement in both the skin and joint symptoms. This case
      illustrates the complex relationship between the host and the HIV, suggesting an
      immune dysregulation cause for both the synovial and the skin lesions.

PMID- 9778233
TI  - Detection of Chlamydia trachomatis in peripheral blood leukocytes of reactive
      arthritis patients by polymerase chain reaction.

PMID- 9778232
TI  - Propionibacterium acnes isolated from synovial tissue and fluid in a patient with
      oligoarthritis associated with acne and pustulosis.
AB  - This report describes the case of a patient with a 14-month course of severe
      oligoarthritis associated with acne. Pure cultures of Propionibacterium acnes
      were isolated from synovial tissue and synovial fluid specimens collected from
      the same joint after a 4-month interval. After 2 months of treatment with
      roxithromycin 300 mg/day, rifampicin 1,200 mg/day, and a nonsteroidal
      antiinflammatory drug (NSAID), followed by 4 months of treatment with
      azithromycin 1 gm/week and an NSAID, the synovitis persisted. Cultures of skin
      lesions and synovial fluid at this time were negative. Although P acnes has
      previously been isolated from bone specimens obtained from patients with osteitis
      associated with acne, this is the first report of the isolation of this
      microorganism from the synovial tissue of a patient with arthritis associated
      with acne. Our findings raise the question of the role of P acnes in the
      pathogenesis of arthritis associated with acne.

PMID- 9778234
TI  - Clinical image: bluish discoloration of the nails in ochronosis.

PMID- 9778235
TI  - Th1/Th2 cytokine balance in arthritis: comment on the article by Miossec and van
      den Berg.

PMID- 9778236
TI  - Role of sex steroids in the Th1/Th2 cytokine balance: comment on the article by
      Miossec and van den Berg.

PMID- 9778237
TI  - Psychosocial outcomes and health status in adults who have had juvenile
      rheumatoid arthritis: comment on the article by Peterson et al.

PMID- 9778238
TI  - Drug-induced pancytopenia in a patient with juvenile HLA-B27-associated
      spondylarthritis: comment on the article by Leipold et al.

PMID- 9778239
TI  - Nuclear inclusions in glutamine repeat disorders: are they pernicious,
      coincidental, or beneficial?

PMID- 9778240
TI  - Signaling to p53: breaking the MDM2-p53 circuit.

PMID- 9778241
TI  - Retroviral superantigens and type 1 diabetes mellitus.

PMID- 9778242
TI  - Development of insulin-dependent diabetes mellitus does not depend on specific
      expression of the human endogenous retrovirus HERV-K.

PMID- 9778243
TI  - HERV-K10s and immune-mediated (type 1) diabetes.

PMID- 9778244
TI  - Ablation of cerebellar Golgi cells disrupts synaptic integration involving GABA
      inhibition and NMDA receptor activation in motor coordination.
AB  - The role of inhibitory Golgi cells in cerebellar function was investigated by
      selectively ablating Golgi cells expressing human interleukin-2 receptor alpha
      subunit in transgenic mice, using the immunotoxin-mediated cell targeting
      technique. Golgi cell disruption caused severe acute motor disorders. These mice
      showed gradual recovery but retained a continuing inability to perform compound
      movements. Optical and electrical recordings combined with immunocytological
      analysis indicated that elimination of Golgi cells not only reduces GABA-mediated
      inhibition but also attenuates functional NMDA receptors in granule cells. These
      results demonstrate that synaptic integration involving both GABA inhibition and
      NMDA receptor activation is essential for compound motor coordination.
      Furthermore, this integration can adapt after Golgi cell elimination so as not to
      evoke overexcitation by the reduction of NMDA receptors.

PMID- 9778245
TI  - Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor
      PTEN.
AB  - PTEN is a tumor suppressor with sequence homology to protein tyrosine
      phosphatases and the cytoskeletal protein tensin. mPTEN-mutant mouse embryos
      display regions of increased proliferation. In contrast, mPTEN-deficient
      immortalized mouse embryonic fibroblasts exhibit decreased sensitivity to cell
      death in response to a number of apoptotic stimuli, accompanied by constitutively
      elevated activity and phosphorylation of protein kinase B/Akt, a crucial
      regulator of cell survival. Expression of exogenous PTEN in mutant cells restores
      both their sensitivity to agonist-induced apoptosis and normal pattern of PKB/Akt
      phosphorylation. Furthermore, PTEN negatively regulates intracellular levels of
      phosphatidylinositol (3,4,5) trisphosphate in cells and dephosphorylates it in
      vitro. Our results show that PTEN may exert its role as a tumor suppressor by
      negatively regulating the PI3'K/PKB/Akt signaling pathway.

PMID- 9778246
TI  - Ataxin-1 nuclear localization and aggregation: role in polyglutamine-induced
      disease in SCA1 transgenic mice.
AB  - Transgenic mice carrying the spinocerebellar ataxia type 1 (SCA1) gene, a
      polyglutamine neurodegenerative disorder, develop ataxia with ataxin-1 localized
      to aggregates within cerebellar Purkinje cells nuclei. To examine the importance
      of nuclear localization and aggregation in pathogenesis, mice expressing ataxin
      1[82] with a mutated NLS were established. These mice did not develop disease,
      demonstrating that nuclear localization is critical for pathogenesis. In a second
      series of transgenic mice, ataxin-1[77] containing a deletion within the self
      association region was expressed within Purkinje cells nuclei. These mice
      developed ataxia and Purkinje cell pathology similar to the original SCA1 mice.
      However, no evidence of nuclear ataxin-1 aggregates was found. Thus, although
      nuclear localization of ataxin-1 is necessary, nuclear aggregation of ataxin-1 is
      not required to initiate pathogenesis in transgenic mice.

PMID- 9778247
TI  - Huntingtin acts in the nucleus to induce apoptosis but death does not correlate
      with the formation of intranuclear inclusions.
AB  - The mechanisms by which mutant huntingtin induces neurodegeneration were
      investigated using a cellular model that recapitulates features of
      neurodegeneration seen in Huntington's disease. When transfected into cultured
      striatal neurons, mutant huntingtin induces neurodegeneration by an apoptotic
      mechanism. Antiapoptotic compounds or neurotrophic factors protected neurons
      against mutant huntingtin. Blocking nuclear localization of mutant huntingtin
      suppressed its ability to form intranuclear inclusions and to induce
      neurodegeneration. However, the presence of inclusions did not correlate with
      huntingtin-induced death. The exposure of mutant huntingtin-transfected striatal
      neurons to conditions that suppress the formation of inclusions resulted in an
      increase in mutant huntingtin-induced death. These findings suggest that mutant
      huntingtin acts within the nucleus to induce neurodegeneration. However,
      intranuclear inclusions may reflect a cellular mechanism to protect against
      huntingtin-induced cell death.

PMID- 9778248
TI  - Specification of motor neuron identity by the MNR2 homeodomain protein.
AB  - Sonic hedgehog signaling controls the differentiation of motor neurons in the
      ventral neural tube, but the intervening steps are poorly understood. A
      differential screen of a cDNA library derived from a single Shh-induced motor
      neuron has identified a novel homeobox gene, MNR2, expressed by motor neuron
      progenitors and transiently by postmitotic motor neurons. The ectopic expression
      of MNR2 in neural cells initiates a program of somatic motor neuron
      differentiation characterized by the expression of homeodomain proteins, by
      neurotransmitter phenotype, and by axonal trajectory. Our results suggest that
      the Shh-mediated induction of a single transcription factor, MNR2, is sufficient
      to direct somatic motor neuron differentiation.

PMID- 9778249
TI  - G protein signaling events are activated at the leading edge of chemotactic
      cells.
AB  - Directional sensing by eukaryotic cells does not require polarization of
      chemoattractant receptors. The translocation of the PH domain-containing protein
      CRAC in D. discoideum to binding sites on the inner face of the plasma membrane
      reflects activation of the G protein-linked signaling system. Increments in
      chemoattractant elicit a uniform response around the cell periphery. Yet when
      cells are exposed to a gradient, the activation occurs selectively at the
      stimulated edge, even in immobilized cells. We propose that such localized
      activation, transmitted by the recruitment of cytosolic proteins, may be a
      general mechanism for gradient sensing by G protein-linked chemotactic systems
      including those involving chemotactic cytokines in leukocytes.

PMID- 9778250
TI  - A SWI/SNF-related chromatin remodeling complex, E-RC1, is required for tissue
      specific transcriptional regulation by EKLF in vitro.
AB  - Erythroid Kruppel-like factor (EKLF) is necessary for stage-specific expression
      of the human beta-globin gene. We show that EKLF requires a SWI/SNF-related
      chromatin remodeling complex, EKLF coactivator-remodeling complex 1 (E-RC1), to
      generate a DNase I hypersensitive, transcriptionally active beta-globin promoter
      on chromatin templates in vitro. E-RC1 contains BRG1, BAF170, BAF155, and INI1
      (BAF47) homologs of yeast SWI/SNF subunits, as well as a subunit unique to higher
      eukaryotes, BAF57, which is critical for chromatin remodeling and transcription
      with EKLF. E-RC1 displays functional selectivity toward transcription factors,
      since it cannot activate expression of chromatin-assembled HIV-1 templates with
      the E box-binding protein TFE-3. Thus, a member of the SWI/SNF family acts
      directly in transcriptional activation and may regulate subsets of genes by
      selectively interacting with specific DNA-binding proteins.

PMID- 9778251
TI  - Bean Dwarf mosaic geminivirus movement proteins recognize DNA in a form- and size
      specific manner.
AB  - Plant viral movement proteins mediate the cell-to-cell movement of nucleic acids.
      This involves either a direct interaction between the viral movement protein and
      the nucleic acid or an indirect interaction involving host factors. The bipartite
      geminiviruses possess two movement proteins, BV1 and BC1, that coordinate
      movement of viral DNA across nuclear and plasmodesmal boundaries, respectively.
      Here, we demonstrate that both BV1 and BC1 interact directly with DNA and, in
      addition, that they have the unique property to recognize DNA on the basis of
      form and size rather than sequence. This is a novel feature for plant virus
      movement proteins and raises the possibility that BV1 and BC1 may be determinants
      of genome size in the bipartite geminiviruses.

PMID- 9778252
TI  - RNA-assisted nuclear transport of the meiotic regulator Mei2p in fission yeast.
AB  - Fission yeast Mei2p is an RNA-binding protein required for both premeiotic DNA
      synthesis and meiosis I. Mei2p binds to a polyadenylated RNA molecule, meiRNA,
      loss of which blocks meiosis I. Mei2p forms a dot in meiotic prophase nuclei.
      Here, we show that meiRNA is required for the nuclear localization of Mei2p and
      is detectable in the dot. However, Mei2p carrying a nuclear localization signal
      can produce a nuclear dot and promote meiosis I in the absence of meiRNA. Mei2p
      expressed in cultured mammalian cells stays in the cytoplasm, but it accumulates
      in the nucleolus if meiRNA is coexpressed. These results indicate that meiRNA
      contributes to the promotion of meiosis I exclusively as a cofactor that assists
      nuclear transport of Mei2p.

PMID- 9778253
TI  - Tn10 transposition via a DNA hairpin intermediate.
AB  - We present evidence that excision of the nonreplicative transposon Tn10 involves
      three distinct chemical steps, first-strand nicking, hairpin formation, and
      hairpin resolution. This three-step mechanism makes it possible for a single
      protein-active site to cleave two DNA strands of opposite polarity, as appears to
      be the case in this reaction. We infer the existence of alternating
      bifunctionality within the active site with suitable modulation of substrate
      components between steps. DNA double-strand breaks are also made by a "hairpin
      mechanism" in V(D)J recombination, possibly reflecting the same basic constraints
      faced in the Tn10 system. Similarities in the basic chemical steps in Tn10
      transposition and V(D)J recombination suggest that the V(D)J mechanism may have
      evolved from a bacterial transposition system.

PMID- 9778255
TI  - Stress genes protect brain.

PMID- 9778254
TI  - Structure of the DNA repair and replication endonuclease and exonuclease FEN-1:
      coupling DNA and PCNA binding to FEN-1 activity.
AB  - Flap endonuclease (FEN-1) removes 5' overhanging flaps in DNA repair and
      processes the 5' ends of Okazaki fragments in lagging strand DNA synthesis. The
      crystal structure of Pyrococcus furiosus FEN-1, active-site metal ions, and
      mutational information indicate interactions for the single- and double-stranded
      portions of the flap DNA substrate and identify an unusual DNA-binding motif. The
      enzyme's active-site structure suggests that DNA binding induces FEN-1 to clamp
      onto the cleavage junction to form the productive complex. The conserved FEN-1 C
      terminus binds proliferating cell nuclear antigen (PCNA) and positions FEN-1 to
      act primarily as an exonuclease in DNA replication, in contrast to its
      endonuclease activity in DNA repair. FEN-1 mutations altering PCNA binding should
      reduce activity during replication, likely causing DNA repeat expansions as seen
      in some cancers and genetic diseases.

PMID- 9778256
TI  - Gene therapy with HSP72 is neuroprotective in rat models of stroke and epilepsy.
AB  - Brain areas damaged by stroke and seizures express high levels of the 72-kd heat
      shock protein (HSP72). Whether HSP72 represents merely a marker of stress or
      plays a role in improving neuron survival in these cases has been debated. Some
      induced tolerance experiments have provided correlative evidence for a
      neuroprotective effect, and others have documented neuroprotection in the absence
      of HSP72 synthesis. We report that gene transfer therapy with defective herpes
      simplex virus vectors overexpressing hsp72 improves neuron survival against focal
      cerebral ischemia and systemic kainic acid administration. HSP72 overexpression
      improved striatal neuron survival from 62.3 to 95.4% in rats subjected to 1 hour
      of middle cerebral artery occlusion, and improved survival of hippocampal dentate
      gyrus neurons after systemic kainic acid administration, from 21.9 to 64.4%. We
      conclude that HSP72 may participate in processes that enhance neuron survival
      during transient focal cerebral ischemia and excitotoxin-induced seizures.

PMID- 9778258
TI  - Posterior vermal split syndrome.
AB  - We have studied a battery of movements in 5 children (age, 6-15 years) after
      transection of the posterior inferior cerebellar vermis. In each case, the
      surgery destroyed the midline vermis only (ranging from lobules VI-X). Tandem
      gait was badly impaired in all subjects. No subjects had impairments of kicking,
      reaching, pinching, or speech. Regular gait, standing, and hopping on one leg
      were relatively unimpaired. Cutting the parallel fibers that cross the midline
      may be the critical variable causing incoordination in tandem gait.

PMID- 9778257
TI  - Matrix metalloproteinases contribute to the blood-brain barrier disruption during
      bacterial meningitis.
AB  - In this study, we investigated the involvement of matrix metalloproteinases
      (MMPs) in the pathophysiology of bacterial meningitis. By using an enzyme
      immunoassay, high concentrations of MMP-9 were detected in the cerebrospinal
      fluid (CSF) of adult patients with bacterial meningitis but not in controls, and
      in patients with Guillain-Barre syndrome. Moreover, we observed significantly
      elevated concentrations of the tissue inhibitor of metalloproteinase-1 (TIMP-1)
      in the CSF of patients with bacterial meningitis, compared with controls. In a
      rat model of meningococcal meningitis, intracisternal injection of heat-killed
      meningococci caused a disruption of the blood-brain barrier (BBB), an increase in
      intracranial pressure, and CSF pleocytosis paralleled by the occurrence of MMP-9
      activity in the CSF 6 hours after meningococcal challenge. The MMP inhibitor
      batimastat (BB-94) significantly reduced the BBB disruption and the increase in
      intracranial pressure irrespective of the time of batimastat administration (15
      minutes before and 3 hours after meningococcal challenge) but failed to
      significantly reduce CSF white blood cell counts. In conclusion, our results
      suggest that MMPs are involved in the alterations of BBB permeability during
      experimental meningococcal meningitis.

PMID- 9778259
TI  - Expression of integrins in experimental autoimmune neuritis and Guillain-Barre
      syndrome.
AB  - Integrins are a subclass of adhesion molecules that mediate cell-cell and cell
      extracellular matrix interactions. Integrins influence transendothelial migration
      of lymphocytes and monocytes and are suitable targets for experimental
      immunotherapy. They are critically involved in the pathogenesis of autoimmune
      neuritis and abnormally expressed in human neuropathies. Also, the role of
      integrins in myelination, neurite outgrowth, and nerve regeneration suggests that
      they could be involved in the recovery phase of immune-mediated neuropathies. We
      investigated by immunohistochemistry the expression of a number of integrin
      subunits during the course of experimental autoimmune neuritis (EAN). Results
      were compared with the human immune neuropathy Guillain-Barre syndrome (GBS) and
      extended in vitro. Inflammation and demyelination in both EAN and GBS induced the
      down-regulation of beta4 integrin in Schwann cells (SCs), whereas loss of alpha2
      was noted only in EAN. When axonal loss was present, SCs displayed alpha5
      integrin, in both EAN and GBS. In vitro, basal lamina and inflammatory cytokines
      modulated the expression of beta4 in SCs, but they did not influence alpha2 and
      alpha5 expression. Finally, integrins were differentially expressed in blood
      vessels during EAN. In conclusion, the spatiotemporal changes in integrin
      expression may be used to characterize, stage, and better understand the
      pathogenesis and evolution of inflammation during GBS and EAN. This may help to
      establish useful, novel therapy for immune-mediated neuropathies.

PMID- 9778260
TI  - Neurophysiological identification of the subthalamic nucleus in surgery for
      Parkinson's disease.
AB  - Microelectrode recording methods for stereotactic localization of the subthalamic
      nucleus (STN) and surrounding structures are described. These methods accurately
      define targets for chronic deep brain stimulation in the treatment of Parkinson's
      disease. Mean firing rates and a burst index were determined for all recorded
      neurons, and responses to active and passive limb and orofacial movements were
      tested. STN neurons had a mean firing rate of 37+/-17 Hz (n = 248) and an
      irregular firing pattern (median burst index, 3.3). Movement-related activity and
      tremor cells were identified in the STN. Ventral to the STN, substantia nigra
      pars reticulata neurons had a mean rate of 71+/-23 Hz (n = 56) and a more regular
      firing pattern (median burst index, 1.7). Short trains (1-2 seconds) of
      electrical microstimulation of STN could produce tremor arrest but were not found
      to be useful for localization. Compared with data from normal monkeys our
      findings suggest that STN neuronal activity is elevated in Parkinson's disease.

PMID- 9778261
TI  - A subgroup of multiple sclerosis patients with anticardiolipin antibodies and
      unusual clinical manifestations: do they represent a new nosological entity?
AB  - The presence of antibodies to cardiolipin (ACL Abs) has been reported in some
      patients suffering from multiple sclerosis (MS), especially of the
      "neuromyelitic" type. In addition, bright T2-imaging foci (unidentified bright
      objects) are occasionally detected on brain magnetic resonance imaging (MRI)
      scans, in patients with antiphospholipid syndrome. From a cohort of 100 patients
      with a probable or definite diagnosis of MS according to Poser's criteria, we
      isolated a subgroup of 20 patients (8 males and 12 females) consistently positive
      for ACL Abs. These patients were followed up neurologically for 1 to 3 years and
      brain MRI scanning and a complete autoimmune screening were performed. Nineteen
      (19 of 20) of our patients had the classic neuroimaging features of MS (multiple
      white-matter T2 bright foci on the MRI scan). The most common neurological
      syndrome was chronic, slowly progressing myelopathy (presenting as myelopathy,
      neuromyelitis optica, or spinocerebellar syndrome; 15 of 20), and optic
      neuropathy (6 of 20). Headache was a dominant symptom in 8 of 20 patients. Less
      common symptoms included cognitive and psychiatric disorders and chronic fatigue.
      The mean levels of ACL Abs were 38.8+/-28.2 GPL (normal values up to 7.5).
      Oligoclonal bands in the cerebrospinal fluid were detected in only 3 of 20
      patients. Patients were treated with acetylsalycilic acid and occasionally with
      short courses of steroids. The progression of the chronic
      myelopathic/spinocerebellar syndrome was slower than expected in MS (only 2
      patients deteriorated whereas 4 improved during a mean follow-up period of 20.8+/
      7.1 months). We conclude that patients with probable or definite diagnosis of MS,
      and consistently elevated levels of ACL Abs show a slower progression and some
      atypical (for MS) features, such as persistent headaches and absence of
      oligoclonal bands in the cerebrospinal fluid. In these patients, other,
      presumably vascular, mechanisms may be involved in the pathogenesis of the
      neurological symptoms. Therefore, management should include antiplatelet or even
      anticoagulant agents.

PMID- 9778262
TI  - Progressive myoclonus epilepsy and mitochondrial myopathy associated with
      mutations in the tRNA(Ser(UCN)) gene.
AB  - We report seven unrelated families with mitochondrial tRNA(Ser(UCN)) gene
      mutations at three different loci. A novel G7497A mutation is found in two
      families, both of which present with progressive myopathy, ragged-red fibers,
      lactic acidosis, and deficiency of respiratory chain complexes I and IV. This
      mutation presumably affects the tertiary tRNA(Ser(UCN)) dihydrouridine
      interaction. Mutations 7472 insC and T7512C, found in three and two families,
      respectively, are associated with myoclonus epilepsy, deafness, ataxia, cognitive
      impairment, and complex IV deficiency. No ragged-red fibers or ultrastructural
      abnormalities are seen. It is interesting that 6 of our 7 index patients are
      apparently homoplasmic, indicating a minor pathogenetic power of the
      tRNA(Ser(UCN)) mutations.

PMID- 9778263
TI  - Slow vertical saccades in motor neuron disease: correlation of structure and
      function.
AB  - We studied eye movements and brainstem pathology in 2 patients with slow vertical
      saccades and autopsy-proven amyotrophic lateral sclerosis (ALS). In both
      patients, the main ocular motor finding was supranuclear vertical gaze impairment
      with slow vertical saccades. The second patient had difficulty opening his eyes
      on command, with preserved spontaneous eyelid opening. Postmortem examination in
      both patients demonstrated cell loss in the rostral interstitial nucleus of the
      medial longitudinal fasciculus (riMLF) and substantia nigra, along with
      histopathological findings consistent with ALS. The extent of the pathological
      changes in the riMLF correlated well with the degree of functional impairment as
      reflected in the slow vertical saccades. We suggest that motor neuron disease
      with early involvement of vertical saccades represents a distinct
      clinicopathological entity.

PMID- 9778264
TI  - Dopa-responsive dystonia: a clinical and molecular genetic study.
AB  - We have studied the GTP-cyclohydrolase 1 (GCH-1) gene in 30 patients with the
      diagnosis of clinically definite (n = 20) or possible (n = 10) dopa-responsive
      dystonia (DRD) as well as in a child with atypical phenylketonuria due to
      complete GCH-1 deficiency. A large number of new heterozygote mutations (seven
      point mutations, two splice site mutations, and one deletion) as well as a new
      homozygote mutation in the child with atypical phenylketonuria were detected. In
      addition, two previously described mutations were found in two other cases. We
      further extended our investigation of GCH-1 to the 5' and 3' regulatory regions
      and report the first detection of point mutations in the 5' untranslated region.
      Demethylation of CpG islands does not appear to be an important causative factor
      for the GCH-1 mutations in DRD. In addition, we have extended the clinical
      phenotype of genetically proven DRD to focal dystonia, dystonia with relapsing
      and remitting course, and DRD with onset in the first week of life. None of our
      DRD patients without a mutation in GCH-1 had the 3-bp deletion recently detected
      in DYT1, the causative gene for idiopathic torsion dystonia with linkage to 9q34.

PMID- 9778265
TI  - Acquired slow-channel syndrome: a form of myasthenia gravis with prolonged open
      time of the acetylcholine receptor channel.
AB  - A 32-year-old female presented with a 2-year history of fluctuating generalized
      weakness including extraocular, bulbar, and limb muscles, suggesting myasthenia
      gravis, but with poor response to pyridostigmine and unusual electromyographic
      findings. After rest, power increased on repeated maximal contractions, followed
      by progressive weakness. There were decremental responses at low-frequency
      stimulation, but incremental responses at high frequencies, and single stimuli
      evoked repetitive compound muscle action potentials. Plasmapheresis was
      ineffective. In a conventional assay, antibodies against acetylcholine receptors
      (AChRs) were borderline. However, in an assay using cells expressing mainly adult
      type human AChRs, the patient's serum was positive. Thymectomy revealed a
      hyperplastic thymus. An intercostal muscle specimen revealed small miniature end
      plate potentials, 0.22+/-0.02 mV instead of 0.56+/-0.05 mV in controls. The
      number of 125I-alpha-bungarotoxin binding sites was normal. The decay time
      constant of end-plate potentials was increased from 5.3+/-0.6 msec in controls to
      23+/-3.6 msec in the patient. Ultrastructurally, there was no destruction of the
      end plate. Transfer of the patient's plasma to mice in vivo produced similar
      physiological changes in their diaphragms. We conclude that the patient has an
      immune-mediated disorder, in which an antibody specific to the adult form of the
      AChRs alters the channel properties, reducing total current and slowing the
      closure. We propose the name "acquired slow-channel syndrome" for this variant of
      myasthenia gravis.

PMID- 9778266
TI  - Neonatal cytokines and coagulation factors in children with cerebral palsy.
AB  - We explored the association of inflammatory mediators and markers of autoimmune
      and coagulation disorders with cerebral palsy (CP), examining 53 analytes in
      dried neonatal blood of 31 children with spastic CP, most born at term, and 65
      control children. Ultramicroanalysis was performed by recycling immunoaffinity
      chromatography coupled with laser-enhanced fluorescence and chemiluminescence
      detection. Reactive antibodies to lupus anticoagulant, anticardiolipin,
      antithrombin III, and the translational product of the factor V Leiden mutation
      were isolated by recycling immunoaffinity chromatography and measured by
      capillary electrophoresis with chemiluminescence-enhanced immunoassay. Higher
      concentrations of interleukins (ILs) 1, 8, 9, tumor necrosis factor-alpha, and
      RANTES were observed in these children with CP than in any control child. There
      were also substantial elevations of IL-6, 11, 13, and other chemokines and colony
      stimulating factors in children with CP. Antiphospholipid antibody was present in
      a titer of 1:100 or greater in 4 children with CP and no control child. Using
      cuts empirically chosen by recursive partitioning, we found higher concentrations
      of antibody to antithrombin III, to a translational product of factor V Leiden
      mutation, and to proteins C and S in children with CP than in controls. We
      conclude that inflammation and these coagulation abnormalities, which have
      interacting pathways, are important in the etiology of CP.

PMID- 9778267
TI  - Alpha-ketoglutarate dehydrogenase in Alzheimer brains bearing the APP670/671
      mutation.
AB  - Alzheimer's disease (AD) is associated with a striking reduction in the activity
      of the alpha-ketoglutarate dehydrogenase complex (KGDHC). The deficiency occurs
      in brains from AD patients of undefined etiology, and in fibroblasts from both
      sporadic and familial AD cases. To further assess the nature of the abnormality
      of KGDHC in AD, KGDHC activities and immunoreactivities were analyzed in brains
      from AD patients bearing the Swedish APP670/671 mutation. This gene defect causes
      overproduction of the amyloid beta peptide. KGDHC activities were reduced by 55
      to 57% compared with control values in the mutation-bearing AD cases in the
      medial temporal and superior frontal cortices. The immunochemical levels of KGDHC
      subunits Elk (-51%) and E2k (-76%) declined, whereas E3 concentrations were
      unchanged. The results suggest that mitochondrial dysfunction is a part of the
      pathophysiological process in AD even when the primary pathogenic cause is
      nonmitochondrial.

PMID- 9778268
TI  - Amelioration of flulike symptoms at the onset of interferon beta-1b therapy in
      multiple sclerosis by low-dose oral steroids is related to a decrease in
      interleukin-6 induction.
AB  - Low-dose oral steroid use at the onset of interferon beta-1b (IFNbeta-1b) therapy
      in relapsing-remitting multiple sclerosis (RR-MS) patients reduces flulike
      symptoms. To determine the mechanism by which steroid treatment minimizes these
      side effects, we analyzed the percentage of interleukin-6 (IL-6)-, interferon
      gamma (IFN-gamma)-, tumor necrosis factor alpha (TNF-alpha)-, and IL-10-producing
      cells before and after 3 months of IFNbeta-1b therapy onset. Our results support
      a relationship between IL-6 induction and fever. Such side effects can be
      ameliorated by steroids.

PMID- 9778269
TI  - Antibodies against Helicobacter pylori were detected in the cerebrospinal fluid
      obtained from patients with Guillain-Barre syndrome.
AB  - We examined the antibodies against Helicobacter pylori proteins in the
      cerebrospinal fluid (CSF) of 7 patients with Guillain-Barre syndrome (GBS). Crude
      H. pylori antigens, fractionated heat shock protein (HSP), and urease B (UB) from
      H. pylori antigens were separated by SDS-PAGE. With Western blot analysis, four
      of seven CSF samples had several IgG antibodies against H. pylori proteins,
      including HSP and UB. No cross reactivity against Campylobacter jejuni was
      observed. These antibodies may be involved in the immune responses of patients
      with GBS.

PMID- 9778270
TI  - Ganaxolone, a selective, high-affinity steroid modulator of the gamma
      aminobutyric acid-A receptor, exacerbates seizures in animal models of absence.
AB  - Ganaxolone (3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) is a novel
      neurosteroid which has anticonvulsant properties in a number of seizure models as
      well as the ability to enhance function of the gamma-aminobutyric acid-A
      (GABA(A)) receptor complex via a neurosteroid binding site. The object of these
      experiments was to ascertain the efficacy of ganaxolone against absence seizures.
      Ganaxolone was assessed in the low-dose pentylenetetrazol (PTZ) and the gamma
      hydroxybutyric acid (GHB) model of absence seizures in rats. Ganaxolone
      pretreatment resulted in a significant prolongation of absence seizure in both
      the PTZ and GHB models. Further, ganaxolone in doses above 20 mg/kg alone
      produced bilaterally synchronous spike wave discharges (SWDs) associated with
      behavioral arrest. These data suggest that augmentation of GABA(A) receptor
      complex function by neurosteroids has the potential to result in or exacerbate
      absence seizures.

PMID- 9778271
TI  - Malignant glioma: who benefits from adjuvant chemotherapy?
AB  - We combined two randomized prospective Brain Tumor Study Group data sets to
      analyze the effects of prognostic factors on survival by treatment group.
      Adjuvant chemotherapy increased long-term survival regardless of prognostic
      factors. Pathological review revealed that oligo dendrogliomas were
      overrepresented among long-term survivors independent of therapy. Prognostic
      factors do not predict benefit from adjuvant nitrosourea in malignant gliomas,
      and long-term survival with chemotherapy is not explained by oligodendroglial
      tumors.

PMID- 9778272
TI  - Presence of 4-hydroxynonenal in cerebrospinal fluid of patients with sporadic
      amyotrophic lateral sclerosis.
AB  - A marker of lipid peroxidation 4-hydroxynonenal (HNE) was elevated in the
      cerebrospinal fluid (CSF) of a patient with sporadic amyotrophic lateral
      sclerosis (sALS) compared with that of most patients with other neurological
      diseases. Such elevations of HNE were sufficient to kill cyclic adenosine
      monophosphate (cAMP)-differentiated motor neuron hybrid cells in vitro, and anti
      oxidants prevented this HNE-dependent cell death. These data suggest that
      oxidative stress and lipid peroxidation are associated with and may promote motor
      neuron degeneration in sALS.

PMID- 9778273
TI  - Epilepsia partialis continua associated with a homoplasmic mitochondrial
      tRNA(Ser(UCN)) mutation.
AB  - Epilepsia partialis continua (EPC) is a rare epileptic syndrome characterized by
      continuous focal seizures. We report on a 16-year-old girl who died of prolonged
      pharmacoresistant EPC in whom we identified a 7472insC mutation within the
      mitochondrial transfer ribonucleic acid (tRNA)(ser(UCN)). Additional symptoms
      included ataxia, lactic acidosis, myopathy, sensorineural hearing loss, severe
      headaches, and mental retardation. Quantification revealed 100% mutant
      mitochondrial DNA (mtDNA) in the patient, 4% in her mother, and none in her half
      sister. This highly skewed mtDNA distribution is most improbable (approximately 3
      x 10(-30)) if only explained by random genetic drift. Clustering of dysfunctional
      mitochondria and replicatory advantage of mutant mtDNA may play a role in the
      rapid segregation towards homoplasmy within one generation.

PMID- 9778274
TI  - Central nervous system nitric oxide formation in cerebral systemic lupus
      erythematosus.
AB  - Systemic lupus erythematosus (SLE) is an inflammatory disease in which up to two
      thirds of the patients present neurological symptoms. The diagnosis of the
      disease is based on clinical findings and the presence of autoantibodies, and the
      pathogenesis is unclear. The purpose of this study was to determine if the
      pathogenesis was partly mediated via nitric oxide (NO) formation. Cerebrospinal
      fluid (CSF) samples from 15 patients with cerebral SLE were analyzed for the NO
      metabolites nitrite and nitrate using capillary electrophoresis. The severity of
      neurological symptoms was scored by dividing the patients into two groups with
      either mild or moderate/severe CNS involvement. All patients with cerebral SLE
      showed increased levels of NO metabolites. In CSF, there was a relationship
      between signs of NO production and clinical results showing that increased levels
      of nitrite and nitrate were associated with more severe neurological symptoms.
      These findings may shed new light on the pathogenesis of cerebral SLE, and
      analysis of nitrate and nitrate may prove to be of value in monitoring the
      activity of the disease.

PMID- 9778275
TI  - Genetic polymorphism of the tau gene and neurodegenerative diseases with tau
      pathology among Japanese.

PMID- 9778277
TI  - Joseph H. Ogura Memorial Lecture: educating the American otolaryngologist: 1810
      to 2010.

PMID- 9778276
TI  - Does CAG repeat number predict the rate of pathological changes in Huntington's
      disease?

PMID- 9778278
TI  - Bilateral medialization laryngoplasty.
AB  - OBJECTIVES: To present indications, techniques, and results of bilateral
      medialization laryngoplasty (BML). STUDY DESIGN: Retrospective review of 39
      consecutive patients who had BML for correction of glottal insufficiency
      attributable to presbylaryngis (n = 16), bilateral vocal fold paresis (n = 13),
      unilateral paralysis with contralateral bowing (n = 4), and other miscellaneous
      neurologic diseases (n = 6). METHODS: Complete preoperative and postoperative
      clinical and acoustical data were analyzed for 74% (29/39) of the subjects. All
      39 subjects completed a patient survey to assess their long-term outcomes.
      RESULTS: Overall, 90% (35/39) of the patients who had BML experienced significant
      improvement in voice and swallowing function. Subsequently, 36% (14/39) of the
      patients underwent adjunctive lipoinjection for closure of small residual glottal
      gaps (vocal "fine-tuning"). Of the BML patients (with or without lipoinjection)
      who had complete preoperative and postoperative voice data, 83% (24/29) had
      complete glottal closure after surgery, resulting in normal or near-normal
      voices. Eighty-five percent (33/39) of the patients responded that they "would
      have surgery again." Of the six patients who said that they would not have
      surgery again, three had good results and one had progressive neurologic disease.
      The mean duration of follow-up was 17 months. CONCLUSIONS: BML is an effective
      rehabilitative surgical treatment for symptomatic vocal fold bowing. In addition,
      lipoinjection is useful as an adjunct to BML to enhance the voice outcome in
      selected cases.

PMID- 9778279
TI  - Botulinum toxin management of spasmodic dysphonia (laryngeal dystonia): a 12-year
      experience in more than 900 patients.
AB  - OBJECTIVES: This paper reviews a 12-year experience in more than 900 patients
      with spasmodic dysphonia who have been treated with botulinum toxin. STUDY
      DESIGN: This is a retrospective analysis of patients with adductor spasmodic
      dysphonia (strain-strangled voice), abductor spasmodic dysphonia (whispering
      voice), and adductor breathing dystonia (paradoxical vocal fold motion), all of
      whom have been treated with botulinum toxin injections for relief of symptom.
      METHODS: All of the patients were studied with a complete head and neck and
      neurologic examination; fiberoptic laryngostroboscopy; acoustic and aerodynamic
      measures; and a speech evaluation including the Universal spasmodic dysphonia
      rating scale. Some were given electromyography. All patients received botulinum
      toxin injections into the affected muscles under electromyographic guidance.
      RESULTS: The adductor patients had an average benefit of 90% of normal function
      lasting an average of 15.1 weeks. The abductor patients had an average benefit of
      66.7% of normal function lasting an average of 10.5 weeks. Adverse effects
      included mild breathiness and coughing on fluids in the adductor patients, and
      mild stridor in a few of the abductor patients. CONCLUSION: Botulinum toxin A
      injection of the laryngeal hyperfunctional muscles has been found over the past
      12 years to be the treatment of choice to control the dystonic symptoms in most
      patients with spasmodic dysphonia.

PMID- 9778280
TI  - Use of glycopyrrolate in the treatment of Meniere's disease.
AB  - OBJECTIVES/HYPOTHESIS: The objective of this study was to determine whether
      glycopyrrolate is useful as a vestibular suppressant in patients with Meniere's
      disease. The tested hypotheses were that glycopyrrolate would decrease the
      perception of dizziness measured by the Dizziness Handicap Inventory in patients
      with Meniere's disease and that placebo would cause no such decrease. STUDY
      DESIGN: Randomized, prospective. METHODS: Thirty-seven subjects with a diagnosis
      of Meniere's disease were administered either 2 mg of glycopyrrolate or placebo
      twice daily as needed for vertigo. All were also administered the regimen of 1500
      mg sodium/day diet and diuretic. The following indices were examined: Dizziness
      Handicap Inventory, Tinnitus Handicap Inventory, Modified Somatic Perception
      Questionnaire, Beck Depression Inventory, hearing examination, and
      electronystagmography. After 4 to 6 weeks of the drug regimen, Dizziness Handicap
      Inventory, Tinnitus Handicap Inventory, Modified Somatic Perception
      Questionnaire, and Beck Depression Scale were reexamined. Paired t tests were
      performed to verify the significance of improvement before and after treatment.
      RESULTS: Subjects who received glycopyrrolate had statistically significant
      reduction in Dizziness Handicap Inventory, Beck Depression Score, and Modified
      Somatic Perception Score. In the placebo group, no improvement in any index was
      found. CONCLUSIONS: The hypothesis that glycopyrrolate is a useful vestibular
      suppressant in patients with Meniere's disease was statistically verified.

PMID- 9778281
TI  - Transtympanic gentamicin for Meniere's syndrome.
AB  - OBJECTIVES: Study the impact of transtympanic gentamicin on patients with
      unilateral Meniere's syndrome. Partial chemical labyrinthectomy is a relatively
      recent concept for the treatment of Meniere's syndrome. It uses the ototoxic
      effect of gentamicin to reduce the symptom of vertigo and maintain cochlear
      function. STUDY DESIGN: A prospective study using transtympanic gentamicin was
      begun in January 1994. Patients selected had failed medical therapy, but were not
      incapacitated. Patients had preinjection audiometric and electronystagmography
      data. Most had an imaging study. All had one injection, about half had more than
      one. Patients were seen 1 month after therapy and repeat studies were obtained.
      Repeat injection was performed if indicated. Follow-up from the chart or by
      telephone was obtained. Data were tabulated using the 1995 American Academy of
      Otologaryngology-Head and Neck Surgery guidelines. RESULTS: Through December 1996
      43 patients with unilateral Meniere's syndrome were treated. The pretherapy
      function level was 3 through 5. After therapy the function level was 1 or 2.
      There was almost no change in cochlear function and no patient became deaf. Many
      patients had mild ataxia or dysequilibrium during the first 2 weeks following
      therapy. Most patients showed some decrease in labyrinthine function measured on
      electronystagmography. No attempt was made to ablate labyrinthine function.
      Seventeen of 18 patients had a vertigo index in the class A or B category after 2
      years. CONCLUSIONS: Transtympanic gentamicin has become the treatment of choice
      for patients who fail medical therapy for Meniere's syndrome at the authors'
      institution.

PMID- 9778282
TI  - Split calvarial graft cranioplasty for the prevention of headache after
      retrosigmoid resection of acoustic neuromas.
AB  - OBJECTIVE: This study describes the technique and efficacy of split calvarial
      graft cranioplasty for the reconstruction of retrosigmoid/suboccipital defects
      following surgery for acoustic neuromas. STUDY DESIGN: A prospective study of the
      technique of split calvarial graft cranioplasty, its postoperative healing, and
      incidence of postoperative headache. METHODS: The technique requires splitting of
      the craniotomy bone flap into outer and inner table bone grafts. The combination
      of both bony grafts allows the coverage of a wider area of posterior fossa dura.
      This technique was used in 18 patients. All patients were followed for a minimum
      of 6 months. Eleven of 18 patients were followed for 1 year or longer. Four
      patients had three-dimensional computed tomography of their skull and area of
      split calvarial bone graft. RESULTS: One of 18 patients had a persistent
      disabling headache at 1 year postoperatively. A natural contour of the
      retrosigmoid area was achieved in all patients. Three-dimensional computed
      tomography scan, obtained 6 months postoperatively, showed total coverage of the
      retrosigmoid area and fusion of the bone flap to the surrounding skull.
      CONCLUSION: The technique of split calvarial grafting of posterior fossa defects
      is a feasible, safe, and effective way of separating the nuchal musculature and
      posterior fossa dura. The technique also allows the restoration of the contour
      and bony covering of the retrosigmoid area. The technique is a simple alternative
      to other types of cranioplasties aimed at reducing the incidence of postoperative
      headache in patients with acoustic neuromas.

PMID- 9778283
TI  - Preservation of the stapedius tendon in laser stapes surgery.
AB  - OBJECTIVES/HYPOTHESIS: The stapedius tendon is routinely transected during stapes
      surgery. The objective of this study was to evaluate the technique of stapedial
      tendon preservation during stapes surgery and to compare results of these cases
      with cases where the stapedial tendon was not preserved. STUDY DESIGN:
      Retrospective study. METHODS: Four groups of patients were evaluated. Two groups
      had undergone stapes surgery with preservation of the stapedial tendon. One of
      these groups underwent a laser stapedotomy minus prosthesis (laser STAMP)
      procedure, while the other group had a prosthesis inserted. The other two groups
      had undergone laser stapedotomy with one of two different prostheses being used.
      Audiometric data were obtained and reviewed both preoperatively and at
      approximately 6 weeks postoperatively. RESULTS: All groups had overall successful
      results demonstrating that stapedial tendon preservation is technically possible
      and does not compromise outcomes. CONCLUSIONS: Based on the results, it is
      recommended that the stapedius tendon be preserved whenever possible during laser
      stapes surgery. Reasons justifying its preservation are discussed.

PMID- 9778285
TI  - Long-term hearing results following vestibular surgery in Meniere's disease.
AB  - OBJECTIVES: The purpose of this study is to evaluate the long-term hearing
      changes following vestibular surgery in patients with Meniere's disease. STUDY
      DESIGN: This is a retrospective analysis of patients operated on in a tertiary
      referral center setting. METHODS: Preoperative, postoperative, and 3- to 9-year
      postoperative audiograms were analyzed in two patient groups. Twenty-one patients
      underwent posterior fossa vestibular neurectomy (VN) and five, mastoid
      endolymphatic sac decompression and shunt (ELS). All frequencies, four-frequency
      pure-tone averages (PTAs), spondee thresholds, and speech recognition scores were
      compared for operated ear against nonoperated ear of VN subjects. The results
      were subjected to a covariance analysis. VN and ELS patients whose hearing
      deteriorated from "serviceable" (PTA < or =70 dB hearing level) and speech
      recognition > or =30%) to nonserviceable status were compared using nonparametric
      statistics. RESULTS: Progressive hearing loss beyond the rate of change of the
      normal contralateral ear was evident in all patients. Serviceable hearing dropped
      from 81% to 43% of patients an average of 4 years following VN. CONCLUSIONS: VN
      patients have significant hearing deterioration over time in the operated ear.
      This finding suggests that continued postoperative medical management is
      necessary for patients undergoing VN.

PMID- 9778284
TI  - Lipomas of the internal auditory canal and cerebellopontine angle.
AB  - OBJECTIVE: To evaluate lipomas of the internal auditory canal (IAC) and
      cerebellopontine angle (CPA). STUDY DESIGN: Retrospective review. METHODS: Review
      of a multi-institutional series of 17 lipomas of the IAC/CPA, combined with a
      Medline review of the 67 cases reported in the world literature. RESULTS: This
      series of 17 IAC/CPA lipomas is the largest reported series to date, bringing the
      total number of documented cases to 84. There appears to be a nearly 2:1 male to
      female predominance. Sixty percent were left-sided lesions, and three were
      bilateral. Hearing loss, dizziness, and tinnitus were the most common presenting
      symptoms. Surgical resection was performed in 52 (62%) of these lesions; however,
      total tumor removal was accomplished in only 17 (33%), which is most likely
      because of the fact that these tumors tend to have a poorly defined matrix and a
      dense adherence to neurovascular structures. Sixty-eight percent of patients
      experienced a new deficit postoperatively, 11% were unchanged, and only 19%
      improved with no new deficit. Only one documented case of tumor growth was
      identified; however, the reported follow-up was short (average, less than 3
      years). CONCLUSION: With the magnetic resonance imaging techniques now available,
      lipomas can be reliably differentiated from other masses within the CPA and IAC,
      so histopathologic diagnosis is rarely necessary. Because of the potential for
      significant morbidity with resection of these lesions, we believe that
      conservative follow-up is the best treatment option for patients with these rare
      lesions. Surgery is indicated only when significant progressive or disabling
      symptoms are present.

PMID- 9778286
TI  - Expression of glycoconjugates in human eustachian tubes with otitis media.
AB  - OBJECTIVES: To characterize glycoconjugate expression in normal human eustachian
      tubes and study the alterations in glycoconjugate expression found in eustachian
      tubes with otitis media. STUDY DESIGN: Using lectin histochemistry, alterations
      in glycoconjugates were studied in three normal temporal bones, in four temporal
      bones with mucoid otitis media (MOM), and in five with serous otitis media (SOM).
      METHODS: Sections of previously processed temporal bones were decelloidinized,
      and then incubated with seven biotinylated lectins--WGA, SNA, MAA, BPA, PNA, UEA
      1, and LcH--that reflect seven carbohydrate residues of glycoconjugates,
      respectively: GlcNAc/NeuNAc, NeuNAc alpha(2-6)GalNAc, NeuNAc alpha(2-3)GalNAc,
      Gal beta(1-3) GalNAc, L-fucose, and alpha-mannose residues. Control sections were
      incubated with inhibitory carbohydrates or without biotinylated lectins. RESULTS:
      In the normal temporal bones, five carbohydrate residues in goblet cells and
      cilia of the eustachian tube demonstrated moderate to strong activity--NeuNAc
      alpha(2-6)GalNAc, NeuNAc alpha(2-3)GalNAc, GalNAc, Gal beta(1-3)GalNAc, and L
      fucose. Two residues demonstrated weak activity--GlcNAc/NeuNAc and alpha-mannose.
      Temporal bones with MOM revealed increases in sialic acid and alpha-mannose, and
      a decrease in L-fucose. Residues of carbohydrates in the cilia of bones with SOM
      were notably decreased, especially for GalNAc, Gal beta(1-3)GalNAc, and NeuNAc
      alpha(2-6)GalNAc. CONCLUSIONS: Glycoconjugates in the normal human eustachian
      tube are rich in GalNAc, Gal beta(1-3)GalNAc, L-fucose, and NeuNAc alpha(2-3/2-6)
      GalNAc, but low in alpha-mannose and sialic acid. Eustachian tubes from cases
      with SOM or MOM demonstrated alterations in glycoconjugate expression in cilia
      and goblet cells, which may reflect disorder of the carbohydrate metabolism
      during otitis media, especially in SOM.

PMID- 9778287
TI  - Facial nerve outcome in lateral skull base surgery for benign lesions.
AB  - OBJECTIVE: To statistically identify factors most important in affecting CN7
      outcome in lateral skull base surgery for benign lesions. STUDY DESIGN: A
      retrospective review of 217 nonmalignancy lateral skull base procedures from 1970
      to 1995 at the Otology Group in Nashville. METHODS: Charts were reviewed for
      epidemiology, histopathology, staging, type of CN7 mobilization (none, short,
      long, severance with reanastomosis, and resection), preoperative and
      postoperative CN7 function, surgery performed, and survival. RESULTS: Average
      House-Brackman (HB) scores for mobilizations were as follows: short, 1.65: long,
      2.74: and grafting, 4.33. Factors found to affect outcome in a statistically
      significant fashion were preoperative HB score, staging, type of CN7
      manipulation, and surgical approach. Meningiomas were found to have a worse
      outcome than glomus tumors. CONCLUSIONS: Complete resection of tumors should be
      performed with minimal manipulation of the facial nerve based on regional anatomy
      and tumor anatomy.

PMID- 9778288
TI  - Further evidence for allergic pathophysiology in allergic fungal sinusitis.
AB  - Controversy continues over whether allergic fungal sinusitis represents a true
      allergy, an infection, or a point somewhere along a spectrum between allergy and
      infection. The present study describes two experiments that add weight to the
      argument that allergic fungal sinusitis (AFS) is truly an immunologically
      mediated hypersensitivity and not a form of infection. In the first experiment,
      eight patients with Bipolaris culture-positive AFS were prospectively evaluated
      with Bipolaris antigen skin testing and with inhibition radioallergosorbent
      (RAST) and enzyme-linked immunosorbent assay (ELISA) for Bipolaris-specific IgE
      and IgG antibodies. The Bipolaris AFS cases were compared with 10 control
      patients with no history of AFS. All eight AFS cases demonstrated positive skin
      testing to Bipolaris and in addition, all tested positive by RAST and ELISA for
      IgE and IgG Bipolaris antibodies, respectively. In the control group one patient
      had a positive skin test, ELISA, and RAST and one additional patient had a
      positive ELISA only. Good correlation was noted between skin test, RAST, and
      ELISA results. In the second experiment, sinus mucosa from 14 AFS patients and 10
      control patients with other forms of surgical sinus disease was analyzed by
      immunohistocytochemistry for the eosinophilic inflammatory mediators major basic
      protein (MBP) and eosinophil derived neurotoxin (EDN) and the neutrophil mediator
      neutrophil elastase. All AFS cases demonstrated evidence of eosinophilic mediator
      release, and MBP and EDN predominated over neutrophil elastase. In the control
      group eosinophil and neutrophil mediator release in sinus mucosa was equal. The
      two experiments support the concept that AFS is an antigen-triggered, IgE- and
      IgG-mediated hypersensitivity response with a late-phase inflammatory reaction
      involving release of eosinophilic mediators.

PMID- 9778289
TI  - Minimal-access parathyroid surgery using intraoperative parathyroid hormone
      assay.
AB  - OBJECTIVES: Review the most current preoperative localization imaging techniques
      in patients with primary hyperparathyroidism and demonstrate their applicability
      to targeted tumor removal with intraoperative parathyroid hormone (PTH)
      monitoring. STUDY DESIGN: Retrospective review of 40 consecutive patients
      undergoing parathyroid surgery with intraoperative PTH assay as the principal
      determinant of correction of the hyperparathyroid state. Details of the
      technology, cost analysis, and comparison with other management methods are
      discussed. METHODS: The standard intact PTH chemiluminescent assay (Nichols
      Diagnostics) and modifications to allow accelerated intraoperative results are
      discussed in detail. The time intervals between completion of parathyroid
      excision and postremoval assay and subsequent laboratory investigation present a
      practical therapeutic algorithm. RESULTS: Forty consecutive patients with
      hyperparathyroidism were treated surgically with intraoperative PTH as the
      determinant of satisfactory resolution of the disease state. In most instances,
      the surgical field was reduced to the targeted pathology identified by
      preoperative localization, and all patients became eucalcemic when this method
      was employed. Approximately half of eligible patients were treated under local
      anesthesia. CONCLUSIONS: Intraoperative PTH assay has added a new dimension to
      primary and revision parathyroid surgery. It is cost-effective and accurate and
      may reduce the morbidity of surgical intervention in revision procedures.

PMID- 9778291
TI  - Tracheostomal stenosis revision with simultaneous tracheoesophageal puncture.
AB  - OBJECTIVES/HYPOTHESIS: Vocal rehabilitation of patients who have undergone
      laryngectomy is best accomplished by a tracheoesophageal puncture. Optimal
      function of the prosthesis requires an adequate stoma. Patients with
      tracheostomal stenosis require revision of the stoma if vocal rehabilitation is
      to take place. Revision and tracheoesophageal placement are usually done as two
      separate procedures. Creating a tracheoesophageal fistula at the time of stomal
      revision has not been addressed in the literature. STUDY DESIGN: Prospective
      analysis and follow-up of 10 patients undergoing simultaneous tracheoesophageal
      puncture and stomal revision for tracheostomal stenosis between 1991 and 1996.
      METHODS: Ten patients were reviewed. An inferiorly based V-Y advancement flap was
      used so as not to interfere with the tracheoesophageal puncture. All patients had
      received radiation prior to revision and tracheoesophageal puncture. Patients
      were followed for a minimum of 2 years (range, 2-6 y; median, 3 y). RESULTS: All
      patients maintained an adequate stoma without stenting. Eight of ten patients
      (80%) developed and maintained good tracheoesophageal speech. Two patients had
      their speech fistulas removed. There were no intraoperative or postoperative
      complications. CONCLUSIONS: Creation of a tracheoesophageal fistula at the time
      of stomal revision allows for vocal rehabilitation with a single visit to the
      operating room.

PMID- 9778290
TI  - Intraoperative brachytherapy, laryngopharyngoesophagectomy, and gastric
      transposition for patients with recurrent hypopharyngeal and cervical esophageal
      carcinoma.
AB  - OBJECTIVE: To evaluate the role of laryngopharyngoesophagectomy (LPE),
      intraoperative 125I brachytherapy (IOBT), and gastric transposition (GT) in
      patients with recurrent carcinoma involving the hypopharynx, or cervical
      esophagus. METHODS: Between 1988 and 1994 a total of 21 patients were managed
      with LPE/IOBT/GT. All patients had documentation of recurrent disease at the
      hypopharynx or cervical esophagus and had previously been treated with external
      beam radiation (EBRT) to a total median dose of 60 Gy. Median age was 67 years,
      with 17 male patients and four female. IOBT was performed in all cases with
      permanent 125I implantation. Medical records were retrospectively reviewed.
      Overall survival, local control, and complications were evaluated. Median follow
      up was 6 months. RESULTS: The median activity of 125I was 36 mCi, with a median
      dose of 80 Gy to the region at risk. Fifteen patients had lymph node dissections
      performed in conjunction with LPE, and 10 patients had nodal involvement on
      pathologic examination. Margins were microscopically positive in nine patients,
      and lymphvascular space invasion noted in 13. Actuarial survival at 1 and 3 years
      was 32% and 14%, respectively, with patients alive and with local control at 6,
      24, 36, and 48 months (negative margins). Actuarial local control at 1 and 3
      years was 63%. Complications included fistula in five patients, facial edema in
      four, protracted facial pain in two, cervical abscess in one, and mucosal
      hemorrhage in one. CONCLUSION: Patients with recurrent carcinoma of the
      hypopharynx or cervical esophagus after EBRT have an extremely poor prognosis.
      LPE, IOBT, and GT may provide very good local control for all candidates and
      prolonged survival for a small percentage of patients with an acceptable risk
      profile.

PMID- 9778292
TI  - Malignant neoplastic disease of the parotid lymph nodes.
AB  - OBJECTIVES: To review the management and outcome of patients with malignant
      neoplastic disease of the parotid lymph nodes excluding those with primary
      salivary gland tumors. STUDY DESIGN: Retrospective review of 14 patients who had
      malignant parotid lymph nodes from metastatic cutaneous malignancies, direct
      extension from primary cutaneous malignancies, or lymphoproliferative disorders.
      METHODS: Charts were reviewed from three institutions and tabulated for age,
      gender, histopathology, treatment, and outcome. RESULTS: Fourteen patients met
      the criteria for study. Ten patients had neoplastic nodes from cutaneous
      malignancies. Seven involved squamous cell carcinoma, two were metastatic from
      melanoma, and one was metastatic from basal cell carcinoma. Four patients had
      involvement from lymphoproliferative disorders. CONCLUSIONS: Metastatic disease
      to the parotid nodes or direct extension to nodes from primary cutaneous
      malignancy demonstrates a poor prognosis in this series. Prognosis of
      lymphoproliferative disorder is more favorable.

PMID- 9778293
TI  - Functional laryngeal dyskinesia in children and adults.
AB  - OBJECTIVE: Functional laryngeal dyskinesia (FLD) is characterized by signs and
      symptoms of airway obstruction without anatomic basis. Failure to recognize its
      features often leads to inappropriate diagnostic studies and therapies. A
      systematic approach is presented for the recognition and management of patients
      with this disorder. DESIGN: A retrospective case series at a large, urban
      tertiary care academic hospital. METHODS: Retrospective review of charts of
      adults and children diagnosed with FLD between 1979 and 1996. Presenting symptoms
      and signs of FLD were categorized and methods of diagnosis were recorded.
      Therapeutic interventions and resolution of FLD at follow-up were also analyzed.
      RESULTS: Ten patients were identified with FLD, seven females and three males,
      with mean age of 25.9 years at diagnosis (range, 10-59 y). Patients were
      hospitalized a mean of three times (range, 1 to 6 admissions) before FLD was
      correctly diagnosed. Nine patients were receiving treatment for asthma prior to
      diagnosis. Flow volume loops most often showed a fixed extrathoracic inspiratory.
      Arterial blood gas and radiographic data were essentially normal. The most useful
      diagnostic test was fiberoptic laryngoscopy, which showed abnormal adduction of
      the vocal cords on inspiration in the nine patients in this series who underwent
      laryngoscopy. CONCLUSIONS: The authors' experience with FLD shows that its early
      recognition is associated with fewer interventions and their accompanying risks.
      A high degree of suspicion is required in these patients, who are often young and
      well educated. They present with stridor that may disappear while they are asleep
      or after distraction techniques.

PMID- 9778294
TI  - Clinical update on type II first branchial cleft cysts.
AB  - OBJECTIVE: To describe clinical and radiological signs of type II first branchial
      cleft cyst in order to facilitate diagnosis. METHOD: Report of three cases of
      first branchial cleft cyst type II (one of them in association with ipsilateral
      agenesis of the parotid gland) and review of the literature. RESULTS: Two
      clinical signs are described: the location of the sinus opening in the neck,
      which is situated in a triangle limited by the external auditory canal above, the
      mental region anteriorly, and the hyoid bone inferiorly, and the presence in some
      cases of a myringeal web that runs from the floor of the external auditory canal
      to the umbo. In addition, imaging with computed tomography and magnetic resonance
      of the parotid area may be helpful in confirming the diagnosis.

PMID- 9778296
TI  - Childhood pseudohypacusis in patients with high risk for actual hearing loss.
AB  - OBJECTIVE: While pseudohypacusis or nonorganic hearing loss is a well-recognized
      phenomenon in adults, it is the aim of this report to heighten the physician's
      awareness of the occurrence of nonorganic hearing loss in pediatric patients. The
      medical and otologic histories of 18 cases identified consecutively between 1983
      and 1991 at The Children's Hospital, Boston, Massachusetts, were retrospectively
      reviewed. In these selected cases an analysis of the audiometric configuration,
      age range, and sex distribution is undertaken. This review highlights the need to
      rule out pseudohypacusis even in pediatric cases where suspicion is low. A
      precedent trauma was the presenting complaint in a high percentage of our patient
      population. This association has not been previously reported in the pediatric
      literature. While the severity of the traumatic incident was often minor,
      extensive medical and surgical investigations had been considered before the
      identification of nonorganic hearing loss. STUDY DESIGN: A retrospective chart
      analysis of patients identified with pseudohypacusis over a 7-year period.
      METHODS: A tertiary care children's hospital in an urban community. Eighteen
      consecutively identified patients examined by a staff audiologists at a tertiary
      care children's hospital. A specific battery of standard audiologic testing with
      the goal of detecting pseudohypacusis in children. RESULTS: Successful if
      additional interventions such as exploratory tympanotomy were avoided.
      CONCLUSIONS: Pseudohypacusis was identified in 18 patients with a majority having
      an antecedent history of trauma. Additional interventions were canceled upon the
      detection of true threshold values. A high index of suspicion of pseudohypacusis
      in children and an organized standardized battery of audiologic testing will
      facilitate early identification of these patients and will avert inappropriate
      interventions.

PMID- 9778295
TI  - Th-2 type cytokine receptors in allergic rhinitis and in response to topical
      steroids.
AB  - OBJECTIVES: Th-2 type cytokine production (interleukin-4 [IL-4] and interleukin-5
      [IL-5]) has been demonstrated to play a significant role in the pathophysiology
      of allergic rhinitis (AR), and the treatment of AR with topical corticosteroids
      has been shown to reduce the expression of Th-2 type cytokines in vivo. However,
      the contribution and expression of Th-2 type cytokine receptors in AR and their
      response to corticosteroid treatment remain to be clarified. Objectives of the
      current study are 1. To examine the expression of the cytokine IL-4 and IL-5
      receptors (IL-4R and IL-5R) in a nasal allergen challenge model and to contrast
      this with the expression of the receptor for the Th-1 type cytokine, interferon
      gamma receptor (IFN-gammaR), and 2. to examine the effects of pretreatment with
      topical corticosteroid before allergen challenge on the expression of these same
      receptors. STUDY DESIGN: Randomized prospective study involving 14 ragweed
      allergic subjects evenly divided between placebo and corticosteroid pretreatment.
      METHODS: Immunocytochemistry (alkaline phosphatase-antialkaline phosphatase
      labeling [APAAP] technique) was used to stain nasal biopsy specimens before and
      after allergen challenge. Antibodies used included anti-CD3, CD4, CD8, MBP, IL
      4R, IL-5R, and IFN-gammaR. RESULTS: Following allergen challenge, we observed a
      significant increase in the Th-2 type cytokine receptors (IL-4R and IL-5R; P <
      .05), as well as a significant decrease in the expression of the Th-1 type
      cytokine receptor (IFN-gammaR; P < .05). Pretreatment with topical
      corticosteroids before nasal allergen challenge resulted in decreased expression
      of IL-4R (P < .05) and IL-5R (P < .05) and increased expression of IFN-gammaR (P
      <.05). Further, IL-4R and IL-5R expression correlated with eosinophil
      infiltration in the tissues. CONCLUSIONS: We have demonstrated that in AR,
      cytokine receptors for IL-4, IL-5, and IFN-gamma follow a similar pattern to
      their ligands. In addition, pretreatment with topical corticosteroids was shown
      to alter the cytokine receptor expression pattern from a Th-2 profile more toward
      a Th-1 profile.

PMID- 9778297
TI  - Classification of otitis media.
AB  - OBJECTIVES: To review the International Classification of Diseases (ICD) system
      of classifying otitis media. To highlight the failings of this system and to
      propose an alternative (Read version 3). STUDY DESIGN: An historical review of
      the literature and a presentation of two distinct classification schemes.
      METHODS: The advantages and disadvantages of the alternative schemes are analyzed
      and an algorithm for the classification of otitis media is presented that
      describes the decisions taken to reach a diagnosis. RESULTS: The proposed
      classification of otitis media as used in the Read Codes thesaurus is more
      logical than the ICD classification. CONCLUSIONS: The widely used ICD schema of
      otitis media fails to provide the otologist or general medical practitioner with
      a logically organized set of terms to describe inflammatory middle ear disease.
      This article proposes a simple, hierarchical classification that can be used by
      specialists, generalists and epidemiologists alike.

PMID- 9778298
TI  - A new mutation in the POU3F4 gene in a Japanese family with X-linked mixed
      deafness (DFN3).
AB  - OBJECTIVE: The molecular defect in patients with X-linked mixed deafness showing
      a perilymphatic gusher at stapedectomy (DFN3) has been attributed to mutations in
      the POU3F4 gene. This study aimed to clarify an allelic variant of this gene.
      STUDY DESIGN: This was a genetic study of a single Japanese family with DFN3.
      METHODS: Products of a polymerase chain reaction (PCR) were subjected to single
      strand conformation polymorphism (SSCP) analysis. Direct sequencing of PCR
      products from patients and carriers showing SSCP variants was performed using the
      fluorescent dideoxy termination method and a sequencer. RESULTS: Sequencing of
      the PCR product revealed a 6-base deletion (TTCAAA) at nucleotides 601 to 606,
      resulting in a two-amino-acid deletion in the POU3F4 protein, (phenylalanine and
      lysine at amino acid residues 201 and 202). The deletion was adjacent to the site
      of a nonsense mutation previously described. CONCLUSION: Microdeletions at a
      previously undescribed location account for some clinically important POU3F4
      mutations.

PMID- 9778299
TI  - Ki-67 and p53 in T2 laryngeal cancer.
AB  - OBJECTIVE: To study the relationship between the proliferative capacity,
      represented by the immunohistochemical labeling index (LI) of proliferation
      marker Ki-67, and the p53 status, as in theory an intact p53 cell cycle
      checkpoint system should result in a lower proliferative capacity. STUDY DESIGN:
      From a group of 128 patients with a T2 laryngeal carcinoma, presented from 1989
      to 1993 at the University Hospital Utrecht, 20 patients with recurrent disease
      and 16 patients without recurrent disease were randomly selected. All patients
      received primary irradiation. METHODS: Denaturing gradient gel electrophoresis
      and immunohistochemistry determined the p53 status. MIB-1 staining was used to
      determine the Ki-67 LI. RESULTS: In 36% of specimens we found a p53 mutation with
      overexpression (LI, 31%). In 8% a p53 mutation without p53 overexpression was
      found (LI, 18%). Forty-two percent showed no mutation but, nevertheless,
      overexpression (LI, 35%). Neither mutation nor overexpression was found in 14%
      (LI, 38%). No correlation exists between p53 status and proliferative capacity of
      tumors (analysis of variance [ANOVA]; P = .104). The proliferation rate as
      established with Ki-67 LI positively correlates with response to radiotherapy (P
      = .006). CONCLUSIONS: 1. Overexpression of wild-type p53 protein does not result
      in cell cycle arrest measurable by a lower Ki-67 LI in comparison with cases
      overexpressing mutant type p53 protein. 2. A high Ki-67 LI correlates with a
      favorable response to radiotherapy.

PMID- 9778301
TI  - Fluoroscopically placed percutaneous gastrostomies in the head and neck patient.
AB  - OBJECTIVE: At our institution, percutaneous gastrostomy tubes have been inserted
      under fluoroscopic guidance (fluoroscopic cutaneous gastrostomy [FPG]), thereby
      avoiding the need to traverse the pharynx and esophagus with a large-bore
      esophagoscope. For this reason, placement in the postoperative patient does not
      jeopardize the surgical reconstruction. METHODS: Thirty-five patients underwent
      percutaneous gastrostomy placement under fluoroscopic guidance. These included 12
      patients whose cervical esophagus could not be entered safely because of a lesion
      in the head neck, 11 patients who had recently undergone resection of a head and
      neck cancer with pharyngeal reconstruction where traditional percutaneous enteral
      gastrostomy (PEG) placement was contraindicated, and two patients with
      postoperative fistulae. RESULTS: Thirty-four of 35 patients underwent successful
      gastrostomy or gastrojejunostomy placement. One patient had an intrathoracic
      position of the stomach, and one patient required repeat placement because the
      tube dislodged 5 days after insertion. No tube occluded. CONCLUSIONS:
      Percutaneous gastrostomy under fluoroscopic guidance (FPG) is an effective, safe
      method for access for prolonged enteral feeding of the patient whose cervical
      esophagus cannot be accessed for a variety of reasons. It also allows the safe
      placement of a gastrostomy catheter when the patient's postoperative course
      becomes complicated and prolonged enteral nutrition is required.

PMID- 9778300
TI  - Genotypic analysis of tumor suppressor genes PTEN/MMAC1 and p53 in head and neck
      squamous cell carcinomas.
AB  - OBJECTIVES: Tumor suppressor gene mutations in both p53 and PTEN/MMAC1 genomic
      DNA have been detected in many types of cancer. The purpose of this study was to
      investigate the presence and importance of PTEN/MMAC1 mutations in squamous cell
      carcinomas. METHODS: Exons of each gene were amplified after polymerase chain
      reaction (PCR) using genomic DNA derived from cell lines of squamous cell
      carcinoma of the head and neck (SCCHN) and snap-frozen biopsy specimens from
      primary established head and neck tumors. The amplified and purified DNA was then
      sequenced directly. RESULT: As anticipated, point mutations of the p53 gene were
      found in 80% of cell lines examined. A single base mutation in codon 151 was
      found in six of 10 cell lines studied. PTEN/MMAC1 gene mutations were found in
      neither the cell lines tested nor the tumor biopsy samples. CONCLUSION: This
      study, as well as a large volume of data, confirms that mutations of the p53 gene
      are frequent events in head and neck cancer cell lines. Although PTEN/MMAC1 gene
      mutations have been found in a variety of carcinomas, this gene was not found to
      be mutated in SCCHN cell lines or in primary squamous cell carcinomas of the head
      and neck. This information is useful for further studies of mutations in these
      cell lines.

PMID- 9778302
TI  - Prospective randomized comparative study of tracheoesophageal voice prosthesis:
      Blom-Singer versus Provox.
AB  - OBJECTIVES: Compare the most commonly used types of tracheoesophageal voice
      prostheses, Blom Singer and Provox. STUDY DESIGN: Prospective study of 113
      prostheses placed in 52 patients randomly selected to receive Blom-Singer and
      Provox. METHODS: Postoperative voice was recorded at 1 and 4 months after valve
      placement. Survival time of the prosthesis and four objective voice parameters
      were analyzed. Eight judges rated all recordings in a random order for six
      subjective voice parameters. Subgroup analysis for primary versus secondary
      placements and type of procedure was performed. In addition, patients were asked
      for their subjective assessment. RESULTS: Overall, Blom-Singer and Provox
      prostheses give very similar voice quality, lifetime, and patient satisfaction.
      Cleaning management is somewhat better for Provox, but there is a trend toward
      better overall voice quality for the Blom-Singer prosthesis. In subgroup analysis
      secondarily placed prostheses score somewhat better than primary placements, and
      patients with total laryngectomy have better voices than patients with extended
      laryngectomy combined with partial pharyngectomy. CONCLUSIONS: Given the equal
      and good results in terms of voice quality, other factors (e.g., costs, surgery
      related factors, maintenance, patient preference) should be taken into account
      when deciding which type of tracheoesophageal voice prosthesis to use.

PMID- 9778303
TI  - Quality of life and voice in patients with laryngeal carcinoma: a posttreatment
      comparison of laryngectomy (salvage surgery) versus radiotherapy.
AB  - OBJECTIVES: This study was designed to compare the voice and the quality of life
      (QOL) of laryngeal cancer patients receiving treatment with radical radiotherapy
      with or without laryngectomy as salvage surgery. We also compared the patients'
      own perceptual ratings of their voice to the perceptual ratings of a group of
      listeners. STUDY DESIGN: Two groups of laryngeal cancer patients were studied.
      METHODS: Fourteen irradiated laryngeal speakers with preserved larynx were
      matched with 14 salvage surgery laryngectomized patients speaking with
      tracheoesophageal prosthesis (TEP). To measure patients' QOL, we used the
      European Organisation for Research and Treatment of Cancer Quality of Life Core
      Questionnaire (EORTC QLQ-C30), the EORTC Head and Neck module (EORTC QLQ-H&N35),
      the Hospital Anxiety and Depression scale (HAD) and a study-specific
      questionnaire. For the perceptual speech evaluation we used visual analog scales.
      RESULTS: The perceptual ratings of speech intelligibility, voice quality, and
      speech acceptability showed a significant difference between the treatment
      groups. Both the patients who received treatment with radiotherapy and the
      listeners rated the irradiated laryngeal voices higher than the tracheoesophageal
      speech. The laryngectomized patients scored significantly better than the
      patients treated with radical radiotherapy on the question about hoarseness. No
      other significant difference was found for the QOL functions and symptoms.
      CONCLUSION: When patients treated with radiotherapy were compared with patients
      treated with laryngectomy as salvage surgery, QOL was similar, only small
      differences being found in the perceptual speech evaluation.

PMID- 9778304
TI  - Effects of hemimandibulectomy on quality of life.
AB  - OBJECTIVE: To assess the quality of life and functional status of patients who
      have undergone hemimandibulectomy based on the type of reconstructive procedure
      performed. STUDY DESIGN: Survey, retrospective. METHODS: Twenty-one patients who
      had undergone hemimandibulectomy and had similar defects were divided into two
      groups based on the reconstructive technique utilized. Eleven patients were
      placed in the soft tissue reconstruction group. Ten patients were placed in the
      mandible reconstruction group. All patients were assessed for: function,
      utilizing the Performance Status Scale, and quality of life, using a general
      cancer questionnaire (FACT-G) and a series of questions specific for head and
      neck cancer patients. RESULTS: Mandible reconstruction produced a perceived
      better physical appearance (P = .02), better eating ability (P = .04), and a
      better overall quality of life (P = .002). The mandible reconstruction cohort
      consistently outscored the soft tissue cohort on all questionnaires. CONCLUSION:
      Restoration of mandibular continuity after hemimandibulectomy leads to improved
      function and a superior quality of life in appropriately selected patients.

PMID- 9778305
TI  - 18FDG-PET for the assessment of primary head and neck tumors: clinical, computed
      tomography, and histopathological correlation in 38 patients.
AB  - OBJECTIVES: To evaluate the clinical usefulness of FDG-PET (fluoro-2-deoxy
      glucose-positron emission tomography) in the detection of lymph node involvement
      and recurrences in patients with head and neck cancer. STUDY DESIGN:
      Retrospective review of 38 patients with biopsy-proven head and neck cancers who
      underwent clinical, computed tomography (CT), and FDG-PET examinations. Twenty
      five patients were studied prior to therapy and 13 patients were evaluated for
      disease recurrence. METHODS: All patients were operated and clinical data, CT,
      and FDG-PET results were correlated with histopathological findings. RESULTS: All
      primary tumors in 25 patients were detected, with the exception of one small
      superficial localization of the epiglottis. Histopathological examination showed
      lymph node involvement in 10 patients; PET detected lymph node involvement in
      five. FDG-PET found one case of nodal disease not identified by clinical and CT
      examination. With so few cases, this could be anecdotal. Five false-negative
      results (microscopic lymph node involvement) and two false positives were noted.
      Twelve of 13 patients with recurrent disease were correctly identified with FDG
      PET. FDG-PET was the only imaging technique to identify local recurrence in two
      patients and lymph node involvement in two others. One false-positive result
      occurred in a patient with a foreign body granuloma. CONCLUSIONS: FDG-PET is a
      useful diagnostic modality for the detection of recurrent tumors and, in selected
      cases, precise lymph node involvement. The best way to further investigate the
      utility of clinical FDG-PET is in the follow-up of treated patients.

PMID- 9778306
TI  - Rigid endoscopy for monitoring indirect vocal fold injection.

PMID- 9778307
TI  - Role of quinoids in estrogen carcinogenesis.

PMID- 9778308
TI  - Characterization of a valine-lysine thiourea cross-link on rat globin produced by
      carbon disulfide or N,N-diethyldithiocarbamate in vivo.
AB  - Previous in vivo studies have supported protein cross-linking by CS2 as both a
      mechanism of neurotoxicity and a potential biomarker of effect through the
      detection of a structure responsible for CS2-mediated protein cross-linking,
      namely, lysine-lysine thiourea. In this study, the structure of a previously
      uncharacterized stable protein cross-link produced by CS2 in vivo involving
      lysine and the N-terminal valine of globin has been determined. Rats were exposed
      to 50, 500, and 800 ppm CS2 for 2, 4, 8, and 13 weeks by inhalation or to 3
      mmol/kg N,N-diethyldithiocarbamate administered orally on alternating days for 8
      and 16 weeks. Acid hydrolysis, using 6 N HCl, of globin from control and exposed
      rats caused cyclization of the valine-lysine thiourea cross-link in treated rats
      to isopropyl norleucyl thiohydantoin. The hydrolysate was separated by size
      exclusion chromatography, and the fraction that coeluted with the synthetic
      deuterated isopropyl norleucyl thiohydantoin internal standard was derivatized
      with 3-[4'-(ethylene-N,N, N-trimethylamino)phenyl]-2-isothiocyanate and analyzed
      by liquid chromatography/tandem mass spectrometry using selected reaction
      monitoring detection. Derivatized isopropyl norleucyl thiohydantoin obtained from
      CS2-treated rats displayed a cumulative dose response and was detectable at the
      lowest exposure (50 ppm, 2 weeks) at levels of approximately 50 pmol/g of globin.
      N, N-Diethyldithiocarbamate-treated rats, but not controls, also contained a CS2
      generated valine-lysine thiourea cross-link on globin. In vitro incubation of
      human hemoglobin with either CS2 or N, N-diethyldithiocarbamate also resulted in
      the formation of CS2-generated valine-lysine thiourea. These observations
      demonstrate the potential of thiourea cross-linking involving a free amino
      terminus and epsilon-amino groups of lysine to accumulate in a long-lived
      globular protein and suggest that cross-linking of globin may provide a specific
      dosimeter of internal exposure for CS2 capable of assessing exposure over
      subchronic periods.

PMID- 9778309
TI  - 1,3-Dichloropropene epoxides: intermediates in bioactivation of the promutagen
      1,3-dichloropropene.
AB  - 1,3-Dichloropropene (1,3-D), a major soil fumigant nematicide, is genotoxic in
      many types of assays, leading to its classification as possibly carcinogenic in
      humans. This study tests in three steps the hypothesis that 1,3-D is a promutagen
      activated by epoxidation and further reaction of the 1,3-D-epoxides.
      Stereospecific epoxidation of 1,3-D (examined as the cis/trans mixture and as
      individual isomers) to the corresponding cis- and trans-1,3-D-epoxides is
      demonstrated here for the first time, both in vitro in a mouse liver microsome
      NADPH system and in vivo in the liver of ip-treated mice, using GC/MS for product
      identification and quantitation. The cis epoxide is observed in higher yield than
      the trans epoxide, both in vitro and in vivo, and the cis isomer also reacts
      slower than the trans isomer with GSH alone or catalyzed by GSH S-transferase.
      cis- and trans-1,3-D-Epoxides are stable in acetone or chloroform but degrade
      completely in Me2SO exclusively to 2-chloroacrolein (30 min at 40 degrees C).
      Epoxide decomposition is slower in pH 7.4 phosphate buffer (t1/2 = 116 and 64 min
      for cis and trans, respectively, at 41 degrees C) with a >99% yield of 3-chloro-2
      hydroxypropanal (and its dimer) and <0.5% formation of 2-chloroacrolein (for
      which the t1/2 is 248 min at 41 degrees C). Mutagenicity assays in Salmonella
      typhimurium TA100 (standard plate incorporation) establish high potencies of 37,
      17, and 150 revertants/nmol for cis- and trans-1, 3-D-epoxides and 2
      chloroacrolein, respectively. The mutagenicity of the epoxides is due either to
      their direct action or to a degradation product formed at physiological pH, i.e.,
      3-chloro-2-hydroxypropanal or its dehydrochlorination products. The candidate
      mutagens methylglyoxal and glycidaldehyde are not detected as breakdown products
      of 3-chloro-2-hydroxypropanal at pH 7.4 and also have low mutagenic activity in
      TA100. It is therefore proposed that the penultimate and ultimate mutagens of 1,3
      D metabolism are the corresponding epoxides and their direct hydrolysis product 3
      chloro-2-hydroxypropanal, respectively.

PMID- 9778310
TI  - N-Glycosylation of pig flavin-containing monooxygenase form 1: determination of
      the site of protein modification by mass spectrometry.
AB  - By using a combination of biochemical methods (i.e., endoglycosidase H digestion
      and immunoblot and plant lectin binding studies), it was verified that pig flavin
      containing monooxygenase (FMO1) was N-glycosylated. By using mass spectrometry
      approaches [i.e., peptide mapping, gas chromatography/mass spectrometry,
      microbore HPLC/electrospray ionization mass spectrometry (LC/ESI/MS), chemical
      ionization gas chromatography/mass spectrometry (CI/GC/MS), and matrix-assisted
      laser desorption mass spectrometry (MALDI/MS)], we were able to confirm that pig
      FMO1 was N-glycosylated and we were able to identify the site of N-glycosylation.
      Pig FMO1 contains two putative consensus sites of N-glycosylation. The results
      showed that pig FMO1 amino acid Asn120 was selectively N-glycosylated. Highly
      purified pig FMO1 avidly bound concanavalin A and reacted positively for
      carbohydrates by the periodic acid/Schiff's base method of analysis. In addition,
      treatment of pig FMO1 with endo-N-acetylglucosaminidase converted the enzyme to
      another species with a molecular mass approximately 5000 Da lower than that of
      the parent protein as determined by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) and immunoblot experiments. Peptide mapping of pig
      FMO1 showed that the protein used in the study was not contaminated with another
      glycoprotein. MALDI/MS experiments showed that pig FMO1 was present with the
      expected molecular mass but that higher-molecular mass forms consistent with the
      presence of N-linked high-mannose oligosaccharide structures were also covalently
      attached to the enzyme. The presence of N-acetylglucosamine isolated from acid
      hydrolysates of the N-linked high-mannose oligosaccharide of pig FMO1 was
      confirmed by high-pH anion exchange HPLC studies and verified by CI/GC/MS studies
      of derivatized monosaccharide fractions. Further analysis of pig FMO1 proteolytic
      peptides by LC/ESI/MS showed that the only residue that was N-glycosylated in pig
      FMO1 was Asn120. Knowledge of the structural aspects of FMO may be useful in
      understanding the membrane association properties of the enzyme.

PMID- 9778311
TI  - Inactivation of cytochrome P450 2E1 by tert-butylisothiocyanate.
AB  - Several naturally occurring and synthethic isothiocyanates were evaluated for
      their ability to inactivate the major ethanol-inducible hepatic cytochrome P450
      2E1. Of the compounds tested, tert-butylisothiocyanate (tBITC) was found to be
      the most selective inactivator of the 2E1 p-nitrophenol hydroxylation activity.
      tBITC was more specific for inactivating P450 2E1 activity than for rat P450 1A1,
      1A2, 3A2, and 2B1, or the human cytochromes P450 3A4 and 2B6. The kinetics of
      inactivation of P450 2E1 by tBITC were characterized. P450 2E1, either in rat
      liver microsomes or in a purified reconstituted system containing the bacterially
      expressed rabbit cytochrome, was inactivated by tBITC in a mechanism-based
      manner. The loss of activity followed pseudo-first-order kinetics and was NADPH-
      and tBITC-dependent. The maximal rates for inactivation of P450 2E1 in microsomes
      or for the purified P450 2E1 at 30 degrees C were 0.72 and 0.27 min-1 and the
      apparent KI values were 11 and 7.6 microM, respectively. When cytochrome b5 was
      co-reconstituted with P450 2E1, the apparent KI for P450 2E1 inactivation by
      tBITC was similar to that seen in microsomes (14 microM). P450 2E1 T303A was also
      inactivated by tBITC with kinetic constants similar to that of the wild type
      enzyme. Co-incubations with an alternate substrate protected P450 2E1 from
      inactivation by tBITC. The extent of P450 2E1 inactivation by tBITC resulted in a
      comparable loss of the ability of the enzyme to form a reduced CO complex.

PMID- 9778312
TI  - A monofunctional derivative of melphalan: preparation, DNA alkylation products,
      and determination of the specificity of monoclonal antibodies that recognize
      melphalan-DNA adducts.
AB  - Bifunctional alkylating agents, such as those based on nitrogen mustard, form
      important parts of many anti-cancer chemotherapy protocols and are responsible
      for increased incidences of secondary tumors in successfully treated patients.
      These drugs generally form a majority of monofunctional DNA adducts, although the
      bifunctional adducts appear to be necessary for their powerful cytotoxic and
      antitumor effects. The relative importance of bifunctional as opposed to
      monofunctional adducts in the varied biological consequences of drug exposure has
      not been studied in detail, particularly in relation to the role and specificity
      of biochemical responses to therapy-related DNA damage. A simple method is
      described for the preparation of useful quantities of a pure monofunctional
      derivative of the nitrogen mustard-based drug melphalan. Monohydroxymelphalan was
      prepared by partial hydrolysis, purified by reversed phase chromatography, and
      characterized by MS, NMR, and HPLC. Contamination with melphalan was </=0.2%. The
      heat labile DNA base adducts formed by monohydroxymelphalan were shown to contain
      undetectable levels of cross-linked species. The ratio of adenine to guanine
      adducts was 0.62, similar to the equivalent ratio for melphalan. The sequence
      dependent pattern of alkylation of purified DNA was indistinguishable from that
      of melphalan, but required a higher dose to achieve comparable extents of
      reaction. The specificities of two monoclonal antibodies that recognize melphalan
      DNA adducts were investigated using DNA alkylated with [3H]monohydroxymelphalan.
      Adducts on this DNA showed similar immunoreactivities to adducts formed by
      melphalan. This shows clearly that neither antibody was specific for cross-linked
      adducts and that it is therefore possible to quantify adducts formed by both
      monohydroxymelphalan and melphalan with high sensitivities. The availability of
      monohydroxymelphalan in addition to melphalan, together with sensitive
      immunoassays for adducts on extracted DNA and in individual cells, constitutes a
      useful system for investigating cellular responses to the DNA modifications
      formed by a clinically relevant drug.

PMID- 9778313
TI  - Polyclonal antibodies to adenine N1-oxide: characterization and use for the
      measurement of DNA damage.
AB  - Adenine N1-oxide is a DNA lesion whose formation involves the specific oxidation
      of the adenine base by hydrogen peroxide under nonradical conditions. The damage
      may be measured using a HPLC/32P-postlabeling method, which however cannot be
      used for routine analysis. We propose herein as an alternative an immunological
      assay which allows a rapid evaluation of the level of adenine N1-oxide in DNA
      exposed to oxidative stress. Two polyclonal antibodies were raised using two
      different strategies for the coupling of the hapten to the protein. The first
      approach is based on the universal method of Erlanger and Beiser, whereas the
      preparation of the second antigen involves the conjugation of a morpholino
      derivative of adenosine N1-oxide to the carrier protein. The affinity and the
      specificity of those antibodies were determined by competitive enzyme-linked
      immunosorbent assay. The antibody obtained by the traditional method shows some
      cross-reactivity with normal nucleotides, whereas for the other antiserum, the
      selectivity was found to be higher. Therefore, this polyclonal antibody was used
      to quantify the level of adenine N1-oxide in calf thymus DNA oxidized either by m
      chloroperbenzoic acid or by hydrogen peroxide. The detection limit of the assay
      is four residues of adenine N1-oxide per 10(6) normal bases. The level of adenine
      N1-oxide in nonmodified DNA was lower than the detection limit of the assay,
      whereas in mCPB- and H2O2-modified DNA, it could be up to 14 and 0.7 adenine N1
      oxide residues per 10(4) normal bases, respectively.

PMID- 9778314
TI  - Reactions of 1-methyl-2-phenylindole with malondialdehyde and 4-hydroxyalkenals.
      Analytical applications to a colorimetric assay of lipid peroxidation.
AB  - Under acidic and mild-temperature conditions, 1-methyl-2-phenylindole was found
      to react with malondialdehyde (MDA) and 4-hydroxyalkenals to yield a stable
      chromophore with intense maximal absorbance at 586 nm. The use of methanesulfonic
      acid results in optimal yields of chromophore produced from MDA as well as from 4
      hydroxynonenal. By contrast, the use of hydrochloric acid results in an optimal
      yield of chromophore produced from MDA and a negligible reaction of 4
      hydroxynonenal. Taking advantage of such chromogenic reactions, we developed a
      new colorimetric assay of lipid peroxidation. Using a methanesulfonic acid-based
      medium, MDA and 4-hydroxyalkenals can be measured at the 586 nm wavelength.
      However, the presence of endogenous inhibitors of the reaction with 4
      hydroxyalkenals is common, and this means that the latter may be underestimated
      in some biological samples. The assay performed in a hydrochloric acid-based
      medium enables the specific measurement of MDA in the presence of 4
      hydroxyalkenals. Upon hydrolysis of Schiff bases in hydrochloric acid (pH 1.5),
      either assay can be used to specifically measure the amount of total MDA in
      biological samples because 4-hydroxyalkenals undergo an irreversible cyclization
      reaction under the hydrochloric acid-based conditions of hydrolysis. The two
      assays were applied to the determination of the amount of MDA alone and of MDA
      and 4-hydroxyalkenals in an in vitro model of lipid peroxidation. This
      methodology was also used to clarify complex patterns of tissue-specific MDA
      production in vivo, following hydrolysis of Schiff bases, in rodents treated with
      doxorubicin.

PMID- 9778315
TI  - Reactions of N-methyl-2-phenylindole with malondialdehyde and 4-hydroxyalkenals.
      Mechanistic aspects of the colorimetric assay of lipid peroxidation.
AB  - Under specific acidic conditions, both malondialdehyde (1, MDA) and 4
      hydroxynonenal (2, 4-HNE) react with N-methyl-2-phenylindole (3) to give the same
      chromophoric cyanine 4 with maximal absorbance at 586 nm. Under such conditions,
      the reaction of 3 with 4-HNE (2) as well as with alkanals yields a second
      chromophoric cyanine 10 with maximal absorbance at 505 nm. The influence of
      different acids, iron(III), and oxygen on the reaction of 3 with such aldehydes
      was studied in detail. Under anaerobic conditions, the acid-induced reaction of 4
      HNE with 3 afforded three rapidly interconverting intermediates, 5-7. Their
      subsequent fragmentation to 4 and hexanal in the presence of iron(III) and oxygen
      is consistent with the tandem beta-fragmentation of an indolyl radical cation. 1
      Indolylalkenes were identified as essential intermediates in the acid-induced
      reaction of 3 with alkanals. A very mild iron(III)-catalyzed fragmentation of
      these intermediates afforded the corresponding 3-formylindole 11 as the direct
      precursor of the 505 nm chromophore 10. Such reactions were markedly influenced
      by the nature of the acid. Contrary to the rapid chromogenic reaction of 4-HNE
      which was observed in the presence of methanesulfonic acid, the HCl-induced
      reaction of 4-HNE with 3 did not afford the 586 nm chromophore. Furthermore,
      hexanal did not yield the 505 nm chromophore 10 upon reaction with 3 in the
      presence of HCl, again in contrast with the rapid chromogenic reaction which was
      observed in the presence of methanesulfonic acid. Comparison of the reaction
      mixtures under the two assay conditions confirmed that the same intermediates
      were formed. We conclude that the nature of the acid plays a crucial role in the
      oxidative fragmentation of intermediates into chromophores, allowing the
      selective assay of MDA in the presence of 4-HNE, using HCl acidic conditions.

PMID- 9778316
TI  - Identification of a 2-phenylbenzotriazole (PBTA)-type mutagen, PBTA-2, in water
      from the Nishitakase River in Kyoto.
AB  - We previously isolated five mutagens, compounds I-V, in blue rayon-adsorbed
      materials from the Nishitakase River in Kyoto. The chemical structure of compound
      I, a major mutagen that accounted for 21% of the total mutagenicity, was
      determined to be 2-[2-(acetylamino)-4-[bis(2-methoxyethyl)amino]-5-methoxyphenyl]
      5-am ino-7-bromo-4-chloro-2H-benzotriazole (PBTA-1). Compound II was also a major
      mutagen and accounted for 17% of the total mutagenicity. In this study, a large
      quantity (1.2 mg) of compound II was isolated from adsorbate to 27 kg of blue
      cotton, and its UV, mass, and 1H NMR spectra were analyzed. On the basis of the
      spectral data, compound II was deduced to be the PBTA-1 analogue 2-[2
      (acetylamino)-4-[N-(2-cyanoethyl)ethylamino]-5-methoxyphenyl]-5- amino-7-bromo-4
      chloro-2H-benzotriazole (PBTA-2). As with PBTA-1, PBTA-2 was synthesized from an
      azo dye by reduction and chlorination. Since all of the spectra of PBTA-2
      coincided with those of compound II obtained from river water, compound II was
      concluded to be PBTA-2. PBTA-2 is a newly identified potent mutagen, which
      induces 93 000 and 3 200 000 revertants of Salmonella typhimurium TA98 and YG1024
      per microgram, respectively, in the presence of S9 mix. Like PBTA-1, PBTA-2 may
      also be produced from an azo dye during industrial processes in dyeing factories
      and treatment at sewage plants.

PMID- 9778318
TI  - Characterization of cytochrome P450 3A inactivation by cannabidiol: possible
      involvement of cannabidiol-hydroxyquinone as a P450 inactivator.
AB  - Cannabidiol (CBD) is a major constituent of marijuana and a potent inhibitor of
      P450-mediated hepatic drug metabolism. Mouse P450 3A11 metabolism of [14C]CBD
      resulted in the formation of radiolabeled P450, which after digestion with lysyl
      endopeptidase C (Lys-C) and HPLC resolution of peptides, revealed one major
      broadly eluting peak of radioactivity. Electrophoresis/autoradiography of this
      peak identified several peptide bands, one of which was predominantly
      radiolabeled and had an apparent molecular mass of approximately 6 kDa. Amino
      terminal sequence determination of this band revealed the presence of two
      peptides whose sequences identified them as Ala344-Lys379 and Gly426-Lys454. To
      characterize the reactive species that may be generated during P450 3A11
      catalyzed CBD metabolism, reduced glutathione (GSH) was used as a trapping agent
      for possible electrophilic metabolites. Incubation of P450 3A11 in the presence
      of cofactors NADPH, CBD, and [3H]GSH resulted in the formation of a radiolabeled
      product which was absent in incubations lacking any of the cofactors. The UV
      absorption spectra of this compound indicated absorbances at approximately 220,
      275, and 350 nm, and mass spectral analysis revealed prominent ions at m/z 634,
      599, 505, 402, and 359, ions consistent with that of a GSH adduct of CBD
      hydroxyquinone. A synthetic CBD-hydroxyquinone-GSH adduct was also prepared and
      had UV absorption and mass spectra nearly identical to that of the P450-mediated
      CBD-GSH adduct. CBD-hydroxyquinone formation may be the penultimate oxidative
      step involved in CBD-mediated modification and inactivation of P450 3A11.

PMID- 9778319
TI  - Attomole detection of 3H in biological samples using accelerator mass
      spectrometry: application in low-dose, dual-isotope tracer studies in conjunction
      with 14C accelerator mass spectrometry.
AB  - This is the first demonstration of the use of accelerator mass spectrometry (AMS)
      as a tool for the measurement of 3H with attomole (10(-18) mol) sensitivity in a
      biological study. AMS is an analytical technique for quantifying rare isotopes
      with high sensitivity and precision and has been most commonly used to measure
      14C in both the geosciences and more recently in biomedical research. AMS
      measurement of serially diluted samples containing a 3H-labeled tracer showed a
      strong correlation with liquid scintillation counting. The mean coefficient of
      variation of 3H AMS based upon the analysis of separately prepared aliquots of
      these samples was 12%. The sensitivity for 3H detection in tissue, protein, and
      DNA was approximately 2-4 amol/mg of sample. This high sensitivity is comparable
      to detection limits for 14C-labeled carcinogens using 14C AMS and demonstrates
      the feasibility of 3H AMS for biomedical studies. One application of this
      technique is in low-dose, dual-isotope studies in conjunction with 14C AMS. We
      measured the levels of 3H-labeled 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
      (PhIP) and 14C-labeled 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in
      rat liver tissue and bound to liver DNA and protein 4.5 h following acute
      administration of individual or coadministered doses in the range of 4-5100
      pmol/kg of body weight. Levels of PhIP and MeIQx in whole tissue and bound to
      liver protein were dose-dependent. MeIQx-protein and -DNA adduct levels were
      higher than PhIP adduct levels, which is consistent with their respective
      carcinogenicity in this organ. Coadministration of PhIP and MeIQx did not
      demonstrate any measurable synergistic effects compared to administration of
      these compounds individually. These studies demonstrate the application of AMS
      for the low-level detection of 3H in small biological samples and for its use in
      conjunction with 14C AMS for dual-labeling studies.

PMID- 9778317
TI  - Synthesis of adducts formed by iodine oxidation of aromatic hydrocarbons in the
      presence of deoxyribonucleosides and nucleobases.
AB  - Polycyclic aromatic hydrocarbons (PAH) undergo two main pathways of metabolic
      activation related to the initiation of tumors: one-electron oxidation to give
      radical cations and monooxygenation to yield bay-region diol epoxides. Synthesis
      of standard adducts is essential for identifying biologically formed adducts.
      Until recently, radical cation adducts were synthesized by oxidation of the PAH
      in an electrochemical apparatus, not readily available in many organic chemistry
      laboratories. We have developed a convenient and efficient method for
      synthesizing PAH-nucleoside adducts by using I2 as the oxidant. Adducts of
      benzo[a]pyrene (BP), dibenzo[a, l]pyrene (DB[a,l]P), and 7,12
      dimethylbenz[a]anthracene were synthesized with deoxyguanosine (dG),
      deoxyadenosine, guanine (Gua), or adenine in either Me2SO or dimethylformamide
      (DMF) with or without AgClO4. When, for example, the potent carcinogen BP was
      dissolved in DMF in the presence of 3 equiv of I2, 5 equiv of dG, and 1 equiv of
      AgClO4, 45% of the BP was converted to BP-6-N7Gua. When BP was placed under the
      same reaction conditions in the absence of AgClO4, the extent of formation of BP
      6-N7Gua decreased to 30%. When the potent carcinogen DB[a,l]P was dissolved in
      DMF in the presence of 3 equiv of I2, 5 equiv of dG, and 1 equiv of AgClO4, 43%
      of the DB[a,l]P was converted to DB[a,l]P-10-N7Gua. In the more polar solvent
      Me2SO under the same reaction conditions, however, the yield of DB[a,l]P-10-N7Gua
      was only 20%. Synthesis of adducts with the oxidant I2 is more convenient and, in
      some cases, more efficient than synthesis by electrochemical oxidation. This
      method simplifies the synthesis of PAH-nucleoside and nucleobase adducts that are
      essential for studying biologically formed PAH-DNA adducts.

PMID- 9778320
TI  - Ring addition of the alpha-amino group of glutathione increases the reactivity of
      benzoquinone thioethers.
AB  - 2-(Glutathion-S-yl)-1,4-benzoquinone was found to be remarkably unstable in
      phosphate buffer (pH 7.4) even in the absence of oxygen. Intramolecular addition
      of the alpha-amino group of the glutamate residue to the quinone ring yielded
      ultimately 2,3-(glutathion-N, S-yl)-1,4-benzoquinone and 2,6-(glutathion-N,S-yl)
      1,4-benzoquinone in a 3:1 ratio along with 2-(glutathion-S-yl)-1,4-hydroquinone.
      Kinetic studies indicated that the cyclization reactions proceeded at a rate k1
      of 0.093 min-1, while intermolecular reactions followed a second-order kinetics
      with a k2 of 94 M-1 min-1 (pH 7.4, 37 degreesC), resulting in multiple
      polymerization products. Both intramolecular amino adducts of 2-(glutathion-S-yl)
      1,4-benzoquinone are prone to hydrolysis, leading to the insertion of an
      additional OH group in the ring. These S-substituted trihydroxybenzene
      derivatives are particularly susceptible to autoxidation. The model compound 6-(N
      acetylcystein-S-yl)-2-hydroxy-1,4-hydroquinone was shown to form readily two
      atropoisomeric biphenyls upon autoxidation: 2,4'-bis(N-acetylcystein-S-yl)
      2',3,3',4,6, 6'-hexahydroxybiphenyl, indicating C-C coupling, presumably via
      semiquinone radical intermediates. Thus, the sequence of glutathione S-addition,
      followed by oxidation, N-addition, oxidation, and hydrolysis, constitutes a novel
      and very effective activation pathway of quinones for eliciting oxidative stress.
      These data underline the fact that glutathione conjugates of autoxidizable
      aromatics are no obligatory stable end products of a detoxication reaction. The
      possible toxicological impacts of intra- and intermolecular addition reactions of
      quinoid thiol conjugates are discussed.

PMID- 9778321
TI  - Plaque excision combined with stent placement. Can a poor "finisher" become a
      good "starter".

PMID- 9778322
TI  - New approaches to the management of atrial fibrillation. The role of the atrial
      defibrillator.

PMID- 9778323
TI  - Randomized multicenter comparison of conventional anticoagulation versus
      antiplatelet therapy in unplanned and elective coronary stenting. The full
      anticoagulation versus aspirin and ticlopidine (fantastic) study.
AB  - BACKGROUND: Dual therapy with ticlopidine and aspirin has been shown to be as
      effective as or more effective than conventional anticoagulation in patients with
      an optimal result after implantation of intracoronary metallic stents. However,
      the safety and efficacy of antiplatelet therapy alone in an unselected population
      has not been evaluated. METHODS: Patients were randomized to conventional
      anticoagulation or to treatment with antiplatelet therapy alone. Indications for
      stenting were classified as elective (decided before the procedure) or unplanned
      (to salvage failed angioplasty or to optimize the results of balloon
      angioplasty). After stenting, patients received aspirin and either ticlopidine or
      conventional anticoagulation (heparin or oral anticoagulant). The primary end
      point was the occurrence of bleeding or peripheral vascular complications;
      secondary end points were cardiac events (death, infarction, or stent occlusion)
      and duration of hospitalization. RESULTS: In 13 centers, 236 patients were
      randomized to anticoagulation and 249 to antiplatelet therapy. Stenting was
      elective in 58% of patients and unplanned in 42%. Stent implantation was
      successfully achieved in 99% of patients. A primary end point occurred in 33
      patients (13.5%) in the antiplatelet group and 48 patients (21%) in the
      anticoagulation group (odds ratio=0.6 [95% CI 0.36 to 0.98], P=0.03). Major
      cardiac-related events in electively stented patients were less common (odds
      ratio=0.23 [95% CI 0.05 to 0.91], P=0.01) in the antiplatelet group (3 of 123,
      2.4%) than the anticoagulation group (11 of 111, 9.9%). Hospital stay was
      significantly shorter in the antiplatelet group (4.3+/-3.6 versus 6. 4+/-3.7
      days, P=0.0001). CONCLUSIONS: Antiplatelet therapy after coronary stenting
      significantly reduced rates of bleeding and subacute stent occlusion compared
      with conventional anticoagulation.

PMID- 9778324
TI  - Stenting after optimal lesion debulking (sold) registry. Angiographic and
      clinical outcome.
AB  - BACKGROUND: Coronary stenting has reduced restenosis in focal de novo lesions,
      but its impact has been less pronounced in complex lesion subsets. Preliminary
      data suggest a role for plaque burden in promoting intimal hyperplasia after
      stent implantation. The aim of this study was to test the hypothesis that plaque
      removal with directional atherectomy before stent implantation may lower the
      intensity of late neointimal hyperplasia, reducing the incidence of in-stent
      restenosis. METHODS AND RESULTS: Seventy-one patients with 90 lesions underwent
      directional atherectomy before coronary stenting. Intravascular ultrasound-guided
      stenting was performed in 73 lesions (81%). Clinical success was achieved in 96%
      of patients. Procedural complications were as follows: emergency bypass surgery
      in 1 patient (1.4%), who died 2 weeks later; Q-wave myocardial infarction in 2
      patients (2.8%); and non-Q-wave myocardial infarction in 8 patients (11.3%). None
      of the patients had stent thrombosis at follow-up. Angiographic follow-up was
      performed in 89% of eligible patients at 5.7+/-1.7 months. Loss index was 0.33
      (95% CI, 0.26 to 0.40), and angiographic restenosis was 11% (95% CI, 5% to 20%).
      Clinical follow-up was performed in all patients at 18+/-3 months. Target lesion
      revascularization was 7% (95% CI, 3% to 14%). CONCLUSIONS: Directional
      atherectomy followed by coronary stenting could be performed with good clinical
      success rate. Also, these data point to a possible reduction in angiographic
      restenosis and a significant reduction in the need for repeated coronary
      interventions. Therefore, a randomized clinical trial seems appropriate to test
      the validity of this approach.

PMID- 9778325
TI  - Oral delivery of anticoagulant doses of heparin. A randomized, double-blind,
      controlled study in humans.
AB  - BACKGROUND: Parenteral heparin is the anticoagulant of choice in hospitalized
      patients. Continued anticoagulation is achieved by subcutaneous administration of
      low-molecular-weight heparin or with an orally active anticoagulant such as
      warfarin. An oral heparin formulation would avoid the inconvenience of
      subcutaneous injection and the unfavorable drug interactions and adverse events
      associated with warfarin. A candidate delivery agent, sodium N-[8(-2
      hydroxybenzoyl)amino]caprylate (SNAC), was evaluated with escalating oral heparin
      doses in a randomized, double-blind, controlled clinical study for safety,
      tolerability, and effects on indexes of anticoagulation. METHODS AND RESULTS:
      Increases in activated partial thromboplastin time (aPTT), anti-factors IIa and
      Xa, and tissue factor pathway inhibitor (TFPI) concentrations were detected when
      normal volunteers were dosed with 10.5 g SNAC/20000 IU heparin by gavage in some
      subjects. For the entire group, 30000 IU SNAC and heparin elevated TFPI from
      74.9+/-7.6 to 254.2+/-12.3 mg/mL (P<0.001) 1 hour after dosing (P<0.001). Similar
      changes occurred in anti-factor IIa and anti-factor Xa. aPTT rose from 28+/-0.5
      to 42.2+/-6.3 seconds 2 hours after dosing (P<0.01). No significant changes in
      vital signs, physical examination, ECGs, or clinical laboratory values were
      observed. Neither 30000 IU heparin alone nor 10.5 g SNAC alone altered the
      hemostatic parameters. Emesis was associated with 10.5 g SNAC. A taste-masked
      preparation of SNAC 2.25 g was administered orally with heparin 30000 to 150000
      IU. Both aPTT and anti-factor Xa increased with escalating doses of heparin. This
      preparation was well tolerated. Conclusions-Heparin, administered orally in
      combination with the delivery agent SNAC, produces significant elevations in 4
      indexes of anticoagulant effect in healthy human volunteers. These results
      establish the feasibility of oral delivery of anticoagulant doses of heparin in
      humans and may have broader implications for the absorption of macromolecules.

PMID- 9778326
TI  - Differential effects of glycoprotein IIb/IIIa antagonists on platelet
      microaggregate and macroaggregate formation and effect of anticoagulant on
      antagonist potency. Implications for assay methodology and comparison of
      different antagonists.
AB  - BACKGROUND: Citrated platelet-rich plasma (PRP) turbidimetry is used for
      assessing pharmacodynamic effects of glycoprotein (GP) IIb/IIIa antagonists in
      clinical trials. However, citrate can enhance the potency of at least
      eptifibatide (Integrilin), and turbidimetry is insensitive to microaggregate
      formation. We compared PRP turbidimetry, as a measure of macroaggregate
      formation, with single-platelet counting in both whole blood and PRP as a measure
      of microaggregate formation, using both citrate and hirudin anticoagulation.
      METHODS AND RESULTS: Three GP IIb/IIIa antagonists, eptifibatide, MK-0852, and
      GR144053, were compared in PRP (turbidimetry) and whole blood (platelet counting
      with an Ultra-Flo 100 Platelet Counter), with ADP and collagen used as agonists.
      Compared with hirudin, citrate enhanced the potency of eptifibatide by up to 4
      fold in both PRP and whole blood (P<0.0005), modestly enhanced MK-0852 potency
      (P=0.001), and had no effect on GR144053. Potency measured in PRP was 2- to 3
      fold greater compared with whole blood for MK-0852 and GR144053 but 3- to 4-fold
      greater for eptifibatide. Simultaneous turbidimetry and platelet counting
      performed in PRP indicated that this is because GP IIb/IIIa antagonists are more
      potent inhibitors of in vitro macroaggregation than microaggregation, this effect
      being greater for eptifibatide in hirudinized PRP compared with GR144053
      (P=0.032). CONCLUSIONS: GP IIb/IIIa antagonist potency is variably enhanced by
      citrate. Macroaggregation is inhibited more effectively than microaggregation,
      most markedly in the case of eptifibatide in hirudinized blood. These
      observations have implications for the interpretation and comparison of
      pharmacodynamic assays and possibly for the risk/benefit ratio of different
      agents.

PMID- 9778327
TI  - Use of a prognostic treadmill score in identifying diagnostic coronary disease
      subgroups.
AB  - BACKGROUND: Exercise testing is useful in the assessment of symptomatic patients
      for diagnosis of significant or extensive coronary disease and to predict their
      future risk of cardiac events. The Duke treadmill score (DTS) is a composite
      index that was designed to provide survival estimates based on results from the
      exercise test, including ST-segment depression, chest pain, and exercise
      duration. However, its usefulness for providing diagnostic estimates has yet to
      be determined. METHODS AND RESULTS: A logistic regression model was used to
      predict significant (>/=75% stenosis) and severe (3-vessel or left main) coronary
      artery disease, and a Cox regression analysis was used to predict cardiac
      survival. After adjustment for baseline clinical risk, the DTS was effectively
      diagnostic for significant (P<0.0001) and severe (P<0.0001) coronary artery
      disease. For low-risk patients (score >/=+5), 60% had no coronary stenosis >/=75%
      and 16% had single-vessel >/=75% stenosis. By comparison, 74% of high-risk
      patients (score <-11) had 3-vessel or left main coronary disease. Five-year
      mortality was 3%, 10%, and 35% for low-, moderate-, and high-risk DTS groups
      (P<0.0001). CONCLUSIONS: The composite DTS provides accurate diagnostic and
      prognostic information for the evaluation of symptomatic patients evaluated for
      clinically suspected ischemic heart disease.

PMID- 9778328
TI  - Prospective randomized study of the effect of "add-back" hormone replacement on
      vascular function during treatment with gonadotropin-releasing hormone agonists.
AB  - BACKGROUND: Gonadotropin-releasing hormone agonists (GnRHas) are a group of drugs
      that with long-term use induce a pseudomenopausal state in which estrogen
      production is suppressed. They are commonly used in the treatment of sex steroid
      dependent conditions. "Add-back" hormone replacement therapy is used to prevent
      menopause-like symptoms and bone loss during GnRHa treatment, but it is also
      recognized that hypoestrogenism adversely affects vascular function. The aim of
      this study was to examine the effect of GnRHa and add-back therapy on vascular
      reactivity. This model serves as a paradigm for the effect of hormone replacement
      therapy in postmenopausal women. METHODS AND RESULTS: Measurements of endothelium
      dependent and endothelium-independent vascular reactivity were compared in 2
      groups of women treated with a GnRHa for 6 months. One group received
      estrogen/progestogen add-back therapy during the second 3 months of GnRHa
      treatment. Vascular reactivity was examined by use of ultrasound measurements of
      changes in brachial artery diameter. Endothelium-dependent changes were assessed
      during reactive hyperemia, whereas endothelium-independent changes were measured
      after the administration of glyceryl trinitrate sublingual spray. Treatment with
      the GnRHa alone had an inhibitory effect on endothelium-dependent relaxation.
      However, endothelium-dependent relaxation significantly improved in the group
      receiving add-back therapy (14.6%) compared with the group treated with GnRHa
      alone (8.6%) (P<0.01). There were no significant endothelium-independent changes
      in either group. CONCLUSIONS: These results suggest that the administration of
      add-back therapy has a protective effect on vascular function in GnRHa-induced
      hypoestrogenism. As a model for the menopause, these results also suggest that
      the long-term administration of hormone replacement therapy would result in
      endothelium-dependent arterial relaxation, an observation previously attributed
      only to the acute administration of estrogen.

PMID- 9778329
TI  - Potential benefit from implantable cardioverter-defibrillator therapy in patients
      with and without heart failure.
AB  - BACKGROUND: Whether patients with heart failure derive a benefit from therapy
      with implantable cardioverter-defibrillators (ICDs) has been questioned. The
      purpose of this study was to investigate whether New York Heart Association
      (NYHA) functional class had an impact on the potential benefit from ICD therapy
      as assessed from data stored in the memory of ICDs. METHODS AND RESULTS: Between
      1989 and 1996, 603 patients (77% men; 59% with coronary artery disease and 16%
      with dilated cardiomyopathy; age, 57+/-13 years; ejection fraction, 44+/-18%)
      were treated with an ICD with extended memory function (storage of electrograms
      and/or RR intervals from treated episodes) in combination with endocardial lead
      systems. The stages of heart failure (NYHA functional class I through III) at
      implantation were correlated with overall mortality and the recurrence of fast
      ventricular tachyarrhythmias (>240 bpm) during follow-up. The potential benefit
      of the device was estimated as the difference between overall mortality and the
      hypothetical death rate had the device not been implanted. The latter was based
      on the recurrence of fast and, without termination by the devices, presumably
      fatal ventricular tachyarrhythmias. In the overall group, a significant
      difference between hypothetical death rate and overall mortality was observed
      (13.9%, 23.5%, and 26.6% at 1, 3, and 5 years, respectively) that suggested a
      benefit from ICD implantation. In patients in NYHA class I, the estimated
      benefit, which increased over time, was 15.2%, 29.2%, and 35.6% after 1, 3, and 5
      years, respectively. In patients in NYHA class II or III, the estimated benefit
      increased until the third year (21.8% and 21.9%, respectively) and then remained
      constant until the fifth year (22.9% and 23.8%, respectively). Even those
      patients in NYHA class III with a history of decompensated heart failure
      benefited from ICD implantation. CONCLUSIONS: Analysis of stored ECG data
      suggests that in patients with a history of ventricular tachycardia or
      ventricular fibrillation, ICD therapy may lead to a prolongation of life in NYHA
      classes I through III. The initial benefit is greatest in patients in NYHA class
      II and class III, but the estimated benefit might persist longest for patients in
      NYHA class I.

PMID- 9778330
TI  - Doppler estimation of left ventricular filling pressure in sinus tachycardia. A
      new application of tissue doppler imaging.
AB  - BACKGROUND: Doppler echocardiography is frequently used to predict filling
      pressures in normal sinus rhythm, but it is unknown whether it can be applied in
      sinus tachycardia, with merging of E and A velocities. Tissue Doppler imaging
      (TDI) can record the mitral annular velocity. The early diastolic velocity (Ea)
      behaves as a relative load-independent index of left ventricular relaxation,
      which corrects the influence of relaxation on the transmitral E velocity. METHODS
      AND RESULTS: We evaluated 100 patients 64+/-12 years old with simultaneous
      Doppler and invasive hemodynamics. Mitral inflow was classified into 3 patterns:
      complete merging of E and A velocities (pattern A), discernible velocities with A
      dominance (B), or E dominance (C). The Doppler data were analyzed at the mitral
      valve tips for E, acceleration and deceleration times of E, and isovolumic
      relaxation time. In patterns B and C, the A velocity, E/A ratio, and atrial
      filling fraction were derived. Pulmonary venous flow velocities were also
      measured, and TDI was used to acquire Ea and Aa. Weak significant relations were
      observed between pulmonary capillary wedge pressure (PCWP) and sole parameters of
      mitral flow, pulmonary venous flow, and annular measurements. These were better
      for patterns A and C. E/Ea ratio had the strongest relation to PCWP [r=0.86,
      PCWP=1.55+1.47(E/Ea)], irrespective of the pattern and ejection fraction. This
      equation was tested prospectively in 20 patients with sinus tachycardia. A strong
      relation was observed between catheter and Doppler PCWP (r=0.91), with a mean
      difference of 0.4+/-2.8 mm Hg. CONCLUSIONS: The ratio of transmitral E velocity
      to Ea can be used to estimate PCWP with reasonable accuracy in sinus tachycardia,
      even with complete merging of E and A velocities.

PMID- 9778331
TI  - Atrioverter: an implantable device for the treatment of atrial fibrillation.
AB  - BACKGROUND: During atrial fibrillation, electrophysiological changes occur in
      atrial tissue that favor the maintenance of the arrhythmia and facilitate
      recurrence after conversion to sinus rhythm. An implantable defibrillator
      connected to right atrial and coronary sinus defibrillation leads allows prompt
      restoration of sinus rhythm by a low-energy shock. The safety and efficacy of
      this system, called the Atrioverter, were evaluated in a prospective, multicenter
      study. METHODS AND RESULTS: The study included 51 patients with recurrent atrial
      fibrillation who had not responded to antiarrhythmic drugs, were in New York
      Heart Association Heart failure class I or II, and were at low risk for
      ventricular arrhythmias. The atrial defibrillation threshold had to be </=240 V
      during preimplant testing. Atrial fibrillation detection, R-wave shock
      synchronization, and defibrillation threshold were tested at implantation and
      during follow-up. Shock termination of spontaneous episodes of atrial
      fibrillation was performed under physician observation. Results are given after a
      minimum of 3 months of follow-up. During a follow-up of 72 to 613 days (mean,
      259+/-138 days), 96% of 227 spontaneous episodes of atrial fibrillation in 41
      patients were successfully converted to sinus rhythm by the Atrioverter. In 27%
      of episodes, several shocks were required because of early recurrence of atrial
      fibrillation. Shocks did not induce ventricular arrhythmias. Most patients
      received antiarrhythmic medication during follow-up. In 4 patients, the
      Atrioverter was removed: in 1 because of infection, in 1 because of cardiac
      tamponade, and in 1 because of frequent episodes of atrial fibrillation requiring
      His bundle ablation. CONCLUSIONS: With the Atrioverter, prompt and safe
      restoration of sinus rhythm is possible in patients with recurrent atrial
      fibrillation.

PMID- 9778332
TI  - Apoptosis and cell proliferation after porcine coronary angioplasty.
AB  - BACKGROUND: Angioplasty initiates a number of responses in the vessel wall
      including cellular migration, proliferation, and matrix accumulation, all of
      which contribute to neointima formation and restenosis. Cellular homeostasis
      within a tissue depends on the balance between cell proliferation and apoptosis.
      METHODS AND RESULTS: Profiles of apoptosis and proliferation were therefore
      examined in a porcine PTCA injury model over a 28-day period. Forty-two arteries
      from 21 pigs, harvested at the site of maximal injury at 1, 6, and 18 hours, and
      3, 7, 14, and 28 days after PTCA, were examined (n=3 animals per time point).
      Uninjured arteries were used as controls. Apoptosis was demonstrated by the
      terminal uridine nick-end labeling (TUNEL) method, transmission electron
      microscopy (TEM), and DNA fragmentation. Cells traversing the cell cycle were
      identified by immunostaining for proliferating cell nuclear antigen (PCNA).
      Apoptosis was not detected in control vessels at all time points nor at 28 days
      after PTCA. Apoptotic cells were identified at all early time points with a peak
      at 6 hours (5.1+/-0.26%; compared to uninjured artery, P<0.001) and confirmed by
      characteristic DNA ladders and TEM findings. Regional analysis showed apoptosis
      within the media, adventitia, and neointima peaked at 18 hours, 6 hours, and 7
      days after PTCA, respectively. In comparison, PCNA staining peaked at 3 days
      after PTCA (7.16+/-0.29%; compared to 1.78+/-0.08% PCNA-positive cells in the
      uninjured artery, P<0.001). Profiles of apoptosis and cell proliferation after
      PTCA were discordant in all layers of the artery except the neointima. These
      profiles also differed between traumatized and nontraumatized regions of the
      arterial wall. Immunostaining with cell-type specific markers and TEM analysis
      revealed that apoptotic cells included vascular smooth muscle cells (VSMCs),
      inflammatory cells, and adventitial fibroblasts. CONCLUSIONS: These results
      suggest that the profile of apoptosis and proliferation after PTCA is regional
      and cell specific, and attempts to modulate either of these events for
      therapeutic benefit requires recognition of these differences.

PMID- 9778333
TI  - Chronic amlodipine treatment during the development of heart failure.
AB  - BACKGROUND: This study examined the effects of chronic amlodipine treatment on
      left ventricular (LV) pump function, systemic hemodynamics, neurohormonal status,
      and regional blood flow distribution in an animal model of congestive heart
      failure (CHF) both at rest and with treadmill exercise. In an additional series
      of in vitro studies, LV myocyte contractile function was examined. METHODS AND
      RESULTS: Sixteen pigs were studied under normal control conditions and after the
      development of chronic pacing-induced CHF (240 bpm, 3 weeks, n=8) or chronic
      pacing and amlodipine (1.5 mg . kg-1 . d-1, n=8). Under ambient resting
      conditions, LV stroke volume (mL) was reduced with CHF compared with the normal
      control state (16+/-2 versus 31+/-2, P<0.05) and increased with concomitant
      amlodipine treatment (29+/-2, P<0.05). At rest, systemic and pulmonary vascular
      resistance (dyne . s-1 . cm-5) increased with CHF compared with the normal
      control state (3102+/-251 versus 2156+/-66 and 1066+/-140 versus 253+/-24,
      respectively, both P<0.05) and were reduced with amlodipine treatment (2108+/-199
      and 480+/-74, respectively, P<0.05). With CHF, LV stroke volume remained reduced
      and was associated with a 40% reduction in myocardial blood flow during treadmill
      exercise, whereas chronic amlodipine treatment normalized LV stroke volume and
      improved myocardial blood flow. Resting and exercise-induced plasma
      norepinephrine levels were increased by >5-fold in the CHF group and were reduced
      by 50% from CHF values with chronic amlodipine treatment. Resting plasma
      endothelin (fmol/mL) increased with CHF compared with the normal state (10.4+/
      0.9 versus 3.1+/-0.3, P<0.05) and was reduced with amlodipine treatment (6.6+/
      1.1, P<0.5). With CHF, LV myocyte velocity of shortening ( microm/s) was reduced
      compared with normal controls (39+/-1 versus 64+/-1, P<0.05) and was increased
      with chronic amlodipine treatment (52+/-1, P<0.05). CONCLUSIONS: Chronic
      amlodipine treatment in this model of developing CHF produced favorable
      hemodynamic, neurohormonal, and contractile effects in the setting of developing
      CHF.

PMID- 9778334
TI  - Development of endothelium-dependent relaxation in canine coronary collateral
      arteries.
AB  - BACKGROUND: Little information exists regarding development of vasomotor control
      mechanisms during coronary collateral artery maturation. Therefore, we studied
      endothelium-dependent relaxation of canine collateral arteries isolated 2, 4, and
      9 months after placement of an ameroid occluder around the proximal left
      circumflex coronary artery. RESULTS: Collateral arteries isolated after 2 months
      exhibited markedly reduced endothelium-dependent relaxation in response to
      acetylcholine (ACh; 10(-10) to 10(-4) mol/L) and bradykinin (BK; 10(-11) to 10(
      6) mol/L) compared with relaxation of noncollateral coronary arteries (P<0.01).
      In contrast, endothelium-independent relaxation of collateral arteries to
      nitroprusside was only slightly reduced compared with relaxation of noncollateral
      arteries (P<0.05). Endothelium-dependent relaxation of collateral arteries
      isolated after 4 and 9 months was increased significantly, to the extent that
      relaxation to ACh and BK was not significantly different between collateral and
      noncollateral arteries at these periods. Inhibition of nitric oxide synthesis
      with NT-nitro-L-arginine methyl ester (L-NAME; 100 micromol/L) markedly inhibited
      ACh-induced relaxation in all noncollateral arteries and in collateral arteries
      isolated after 9 months. However, neither L-NAME nor indomethacin (5 micromol/L)
      alone inhibited ACh-mediated relaxation of collateral arteries isolated after 4
      months. ACh-induced relaxation of these collateral arteries was only inhibited
      when arteries were preconstricted with 30 mmol/L K+ and pretreated with L-NAME
      and indomethacin (ie, when synthesis/effects of nitric oxide, prostaglandins, and
      endothelium-derived hyperpolarizing factor were inhibited). CONCLUSIONS:
      Development of endothelium-dependent relaxation in canine coronary collateral
      arteries is not complete after 2 months. After 4 months, endothelium-dependent
      relaxation of collateral arteries is similar to relaxation of noncollateral
      arteries, but the relaxation exhibits decreased dependence on synthesis of nitric
      oxide and increased involvement of prostaglandins and endothelium-derived
      hyperpolarizing factor(s). After 9 months of development, collateral arteries
      exhibit normal nitric oxide-dependent relaxation, similar to noncollateral
      arteries.

PMID- 9778335
TI  - Reduced pulmonary clearance of endothelin-1 contributes to the increase of
      circulating levels in heart failure secondary to myocardial infarction.
AB  - BACKGROUND: The pulmonary vascular bed is a major site for endothelin-1 (ET-1)
      clearance. A reduced clearance could contribute to the increase in circulating ET
      1 levels found in heart failure (HF). We therefore evaluated the effect of HF on
      pulmonary ET-1 clearance and on plasma ET-1 concentrations. METHODS AND RESULTS:
      Rats with myocardial infarction (n=24) were compared with sham-operated rats
      (n=22). The lungs were isolated and perfused at a constant flow rate of 10
      mL/min. Pulmonary ET-1 clearance was measured by the single-bolus indicator
      dilution technique with 125I-labeled ET-1. Infarct rats developed HF with mild
      pulmonary hypertension. ET-1 extraction was reduced by HF from 63+/-1.5% to 41+/
      4.5% (mean+/-SEM, P<0.001). Mixed venous (MV) and aortic ET-1 levels doubled with
      HF. There was a plasma ET-1 gradient across the lungs of sham rats (MV-aortic
      levels, 0.21+/-0.12 pg/mL) but not in lungs of HF rats (0.01+/-0.17 pg/mL).
      Plasma ET-1 levels correlated closely and inversely with ET-1 extraction
      (P<0.001). CONCLUSIONS: HF is associated with reduced pulmonary ET-1 clearance
      that contributes to the increase in circulating levels.

PMID- 9778336
TI  - Quantification of effects of global ischemia on dynamics of ventricular
      fibrillation in isolated rabbit heart.
AB  - BACKGROUND: Ventricular fibrillation (VF) leads to global ischemia of the heart.
      After 1 to 2 minutes of onset, the VF rate decreases and appears more organized.
      The objectives of this study were to determine the effects of no-flow global
      ischemia on nonlinear wave dynamics and establish the mechanism of ischemia
      induced slowing of the VF rate. METHODS AND RESULTS: Activation patterns of VF in
      the Langendorff-perfused rabbit heart were studied with the use of 2 protocols:
      (1) 15 minutes of no-flow global ischemia followed by reperfusion (n=7) and (2)
      decreased excitability induced by perfusion with 5 micromol/L of tetrodotoxin
      (TTX) followed by washout (n=3). Video imaging ( approximately 7500 pixels per
      frame; 240 frames per second) with a voltage-sensitive dye, ECG, and signal
      processing (fast Fourier transform) were used for analysis. The dominant
      frequency of VF decreased from 13.5+/-1.3 during control to 9.3+/-1.4 Hz at 5
      minutes of global ischemia (P<0.02). The dominant frequency decreased from 13.9+/
      1.1 during control to 7.0+/-0.3 Hz at 2 minutes of TTX infusion (P<0.001). The
      rotation period of rotors on the epicardial surface (n=27) strongly correlated
      with the inverse dominant frequency of the corresponding episode of VF (R2=0.
      93). The core area, measured for 27 transiently appearing rotors, was 5.3+/-0.7
      mm2 during control. A remarkable increase in core area was observed both during
      global ischemia (13.6+/-1.7 mm2; P<0.001) and TTX perfusion (16.8+/-3.6 mm2;
      P<0.001). Density of wave fronts decreased during both global ischemia (P<0.002)
      and TTX perfusion (P<0.002) compared with control. CONCLUSIONS: This study
      suggests that rotating spiral waves are most likely the underlying mechanism of
      VF and contribute to its frequency content. Ischemia-induced decrease in the VF
      rate results from an increase in the rotation period of spiral waves that occurs
      secondary to an increase in their core area. Remarkably, similar findings in the
      TTX protocol suggest that reduced excitability during ischemia is an important
      underlying mechanism for the changes seen.

PMID- 9778337
TI  - Left ventricular septal aneurysm.

PMID- 9778338
TI  - Submitral aneurysm.

PMID- 9778339
TI  - A major G protein alpha O isoform in bovine brain is deamidated at Asn346 and
      Asn347, residues involved in receptor coupling.
AB  - The structural differences between two major forms of the alpha subunit of the
      heterotrimeric G protein GO were found to be due to deamidation of either of two
      Asn residues near the C-terminus of the proteins, in a region involved in
      receptor recognition. GO is the most abundant heterotrimeric G protein in
      mammalian brain. Two forms of the protein, GOA and GOB, are known to be generated
      by alternative splicing of a single GOalpha gene. A third isoform, alphaOC,
      represents about 1/3 of the alphaO protein in brain and is related to alphaOA,
      from which it is thought to be generated by protein modification. Mass
      spectrometry and chemical derivatization of tryptic fragments of the proteins
      were used to localize the structural difference between alphaOA and alphaOC to a
      C-terminal peptide. Sequence analysis of a C-terminal chymotryptic fragment both
      by ion trap mass spectrometry and by Edman degradation identified Asn346 and
      Asn347 of alphaOA as alternative deamidation sites in alphaOC. These structural
      differences have immediate implications for G protein function, as they occur in
      a conformationally sensitive part of the protein involved in receptor recognition
      and activation. Since Asn347 is a conserved residue present in most G protein
      alpha subunits outside the alphas family, these observations may have general
      significance for many G proteins. Deamidation may be a component of a novel
      process for modifying or adapting cellular responses mediated by G proteins.

PMID- 9778340
TI  - O2 activation by non-heme diiron proteins: identification of a symmetric mu-1,2
      peroxide in a mutant of ribonucleotide reductase.
AB  - Non-heme diiron clusters occur in a number of enzymes (e.g., ribonucleotide
      reductase, methane monooxygenase, and Delta9-stearoyl-ACP desaturase) that
      activate O2 for chemically difficult oxidation reactions. In each case, a
      kinetically labile peroxo intermediate is believed to form when O2 reacts with
      the diferrous enzyme, followed by O-O bond cleavage and the formation of high
      valent iron intermediates [formally Fe(IV)] that are thought to be the reactive
      oxidants. Greater kinetic stability of a peroxodiiron(III) intermediate in
      protein R2 of ribonucleotide reductase was achieved by the iron-ligand mutation
      Asp84 --> Glu and the surface mutation Trp48 --> Phe. Here, we present the first
      definitive evidence for a bridging, symmetrical peroxo adduct from vibrational
      spectroscopic studies of the freeze-trapped intermediate of this mutant R2.
      Isotope-sensitive bands are observed at 870, 499, and 458 cm-1 that are assigned
      to the intraligand peroxo stretching frequency and the asymmetric and symmetric
      Fe-O2-Fe stretching frequencies, respectively. Similar results have been obtained
      in the resonance Raman spectroscopic study of a peroxodiferric species of Delta9
      stearoyl-ACP desaturase [Broadwater, J. A., Ai, J., Loehr, T. M., Sanders-Loehr,
      J., and Fox, B. G. (1998) Biochemistry 37, 14664-14671]. Similarities among these
      adducts and transient species detected during O2 activation by methane
      monooxygenase hydroxylase, ferritin, and wild-type protein R2 suggest the
      symmetrical peroxo adduct as a common intermediate in the diverse oxidation
      reactions mediated by members of this class.

PMID- 9778341
TI  - Peroxodiferric intermediate of stearoyl-acyl carrier protein delta 9 desaturase:
      oxidase reactivity during single turnover and implications for the mechanism of
      desaturation.
AB  - Combined optical and resonance Raman studies have revealed the formation of an O2
      adduct upon exposure of 4e- chemically reduced stearoyl-acyl carrier protein
      Delta9 desaturase to stearoyl-ACP and 1 atm O2. The observed intermediate has a
      broad absorption band at 700 nm and is remarkably stable at room temperature
      (t1/2 approximately 26 min). Resonance Raman studies using 16O2 gas reveal
      vibrational features of a bound peroxide [Vs(Fe-O2), 442 cm-1; Vas(Fe-O2), 490 cm
      1; V(O-O), 898 cm-1] that undergo the expected mass-dependent shifts when
      prepared in (16)O(18)O or 18(O2). The appearance of two Fe-O2 vibrations, each
      having a single peak of intermediate frequency with 16(O)18(O), provs that the
      peroxide is bound symmetrically between the two iron atoms in a mu-1,2
      configuration. The same results have been obtained in the accompanying resonance
      Raman study of ribonucleotide reductase isoform W48F/D84E [P. Moenne-Loccoz, J.
      Baldwin, B. A. Ley, T. M. Loehr, and J. M. Bollinger, Jr. (1998) Biochemistry 37,
      14659-14663], thus making it likely that other members of the class II diiron
      enzymes form related peroxodiferric intermediates. Study of the reactivity of
      peroxodiferric Delta9D revealed that this intermediate underwent 2e- reduction
      leading to an oxidase reaction and recovery of the resting ferric homodimer. In
      contrast, biological reduction of the same enzyme preparations using ferredoxin
      reductase and [2Fe-2S] ferredoxin gave catalytic desaturation with a turnover
      number of 20-30 min-1. The profound difference in catalytic outcome for
      chemically and enzymatically reduced Delta9D suggests that redox-state dependent
      conformational changes cause partition of reactivity between desaturase and
      oxidase chemistries. The Delta9D oxidase reaction represents a new type of
      reactivity for the acyl-ACP desaturases and provides a two-step catalytic
      precedent for the "alternative oxidase" activity recently proposed for a membrane
      diiron enzyme in plants and trypanosomes.

PMID- 9778342
TI  - The solvent-protected core of the hairpin ribozyme-substrate complex.
AB  - The complex between the hairpin ribozyme and its substrate consists of two
      domains that must interact in order to form a catalytic complex, yet experimental
      evidence concerning the points of interaction between the two domains has been
      lacking. Here, we report the use of hydroxyl radical footprinting to define the
      interface between the two domains. Cations that support very efficient ribozyme
      catalysis (magnesium and cobalt(III) hexammine) lead to the formation of a docked
      complex that features several regions of protection, indicating a solvent
      inaccessible core within the tertiary structure of the complex. Cations that are
      suboptimal in cleavage reactions do not produce complexes with regions of reduced
      solvent accessibility. Nucleotides encompassing the substrate cleavage site (c-2,
      a-1, g+1, and u+2) are strongly protected, suggesting their internalization into
      the catalytic core. Four distinct segments of the ribozyme are protected,
      including G11-A14, C25-C27, A38, and U42-A43. Protection of these sites is
      eliminated when g+1, an essential base at the cleavage site, is replaced by A. In
      addition, mutations which are known to decrease the fraction of docked complexes
      decrease or eliminate formation of a solvent-inaccessible core. Taken together,
      these observations demonstrate that we have identified the catalytic core of the
      active hairpin ribozyme-substrate complex.

PMID- 9778343
TI  - RT loop flexibility enhances the specificity of Src family SH3 domains for HIV-1
      Nef.
AB  - Understanding the issue of specificity imposed in the interactions of SH3 domains
      has largely been addressed in studies investigating the interaction of proline
      rich amino acid sequences derived from potential ligands for these domains.
      Although the interaction with this motif forms an essential platform in the
      binding of SH3 domains, in many cases little specificity is observed and the
      difference in affinity for so-called specific and nonspecific proline-rich
      sequences is not great. Furthermore, the binding interface between an SH3 domain
      and a protein ligand appears to encompass more interactions than are represented
      by that involving the proline-rich motif. Here we investigate the issue of
      specificity from the opposite point of view; namely, how does a ligand recognize
      different SH3 domains? We present the crystal structure of the unbound SH3 domain
      from hemopoietic cell kinase (Hck) which is a member of the Src family of
      tyrosine kinases. This structure reveals that, unlike the structures of other Src
      kinase SH3 domains, the RT loop region is highly mobile and lacks a network of
      hydrogen bonds that is elsewhere apparent. The RT loop has been shown to form a
      major part of the binding interface between SH3 domains and HIV-1 Nef.
      Thermodynamic data, derived from isothermal titration calorimetry, for the
      binding of Hck SH3 to HIV-1 Nef show that the binding of Hck (KD = 1.5 microM) is
      approximately an order of magnitude tighter than those of other Src family
      kinases that were investigated (Fyn, Lck, and Src). This increase in affinity is
      attributed to, among other effects, the inherent flexibility in the RT loop which
      does not require breaking the network of hydrogen bonds to adopt the conformation
      required for binding.

PMID- 9778344
TI  - Crystal structure of 4-oxalocrotonate tautomerase inactivated by 2-oxo-3
      pentynoate at 2.4 A resolution: analysis and implications for the mechanism of
      inactivation and catalysis.
AB  - The crystal structure of 4-oxalocrotonate tautomerase (4-OT) inactivated by the
      active site-directed irreversible inhibitor 2-oxo-3-pentynoate (2-OP) has been
      determined to 2.4 A resolution. The structure of the enzyme covalently modified
      at Pro-1 by the resulting 2-oxo-3-pentenoate adduct is nearly superimposable on
      that of the free enzyme and confirms that the active site is located in a
      hydrophobic region surrounding Pro-1. Both structures can be described as a
      trimer of dimers where each dimer consists of a four-stranded beta-sheet with two
      antiparallel alpha-helices on one side. Examination of the structure also reveals
      noncovalent interactions between the adduct and two residues in the active site.
      The epsilon and eta nitrogens of the guanidinium side chain of Arg-39" from a
      neighboring dimer interact respectively with the C-2 carbonyl oxygen and one C-1
      carboxylate oxygen of the adduct while the side chain of Arg-61' from the same
      dimer as the modified Pro-1 interacts with the C-1 carboxylate group in a
      bidentate fashion. An additional interaction to the 2-oxo group of the adduct is
      provided by one of the two ordered water molecules within the active site region.
      These interactions coupled with the observation that 2-oxo-3-butynoate is a more
      potent irreversible inhibitor of 4-oxalocrotonate tautomerase than is 2-OP
      suggest that Arg-39" and the ordered water molecule polarize the carbonyl group
      of 2-OP which facilitates a Michael reaction between Pro-1 and the acetylene
      compound. On the basis of the crystal structure, a mechanism for the enzyme
      catalyzed reaction is proposed.

PMID- 9778345
TI  - Solution structure of Delta 5-3-ketosteroid isomerase complexed with the steroid
      19-nortestosterone hemisuccinate.
AB  - The solution structure of the ketosteroid isomerase homodimer complexed with the
      product analogue 19-nortestosterone hemisuccinate (19-NTHS) was solved by
      heteronuclear multidimensional NMR methods using 1647 distance restraints, 77
      dihedral angle (phi) restraints, and 67 hydrogen bond restraints per monomer. The
      refined secondary structure of each subunit consists of three alpha-helices,
      eight beta-strands, four turns, and two beta-bulges. The beta-strands form a
      mixed beta-sheet. One of the five proline residues, Pro-39, is cis and begins a
      nonclassical turn. A self-consistent ensemble of 15 tertiary/quaternary
      structures of the enzyme dimer-steroid complex, with no distance violations
      greater than 0.35 A, was generated by simulated annealing and energy minimization
      with the program X-PLOR. The mean pairwise RMSD of the secondary structural
      elements was 0.63 A for the average subunit and 1.25 A for the dimer. Within each
      subunit, the three alpha-helices are packed onto the concave surface of the beta
      sheet with a groove between them into which the steroid binds at a site defined
      by 14 intermolecular distances. In the productive complex, Tyr-14, from alpha
      helix 1, approaches both Asp-99 and the 3-keto group of 19-NTHS while, from beta
      strand 1, the carboxylate of Asp-38 approaches the beta-face of the steroid near
      C4 and C6, between which it transfers a proton during catalysis. Thus the
      solution structure of the isomerase-steroid complex can accommodate the catalytic
      diad mechanism in which Asp-99 donates a hydrogen bond to Tyr-14 which in turn is
      hydrogen bonded to the 3-oxygen of the steroid. While direct hydrogen bonding of
      Asp-99 to the steroid oxygen is less likely, it cannot be excluded. All other
      interactions of the steroid with the enzyme are hydrophobic. The dimer interface,
      which is between the convex surfaces of the beta-sheets, is defined by 28
      intersubunit NOEs between hydrophobic residues in the 13C-filtered NOESY-HSQC
      spectrum of a 13C/12C-heterolabeled dimer. Both hydrophobic and polar
      interactions occur at the dimer interface which contains no space that would
      permit additional steroid binding. Comparison of the complexed enzyme with the
      solution structure of the free enzyme [Wu et al. (1997) Science 276, 415-418]
      reveals that the three helices change position in the steroid complex, becoming
      more closely packed onto the concave surface of the beta-sheet, thus bringing Tyr
      14 closer to Asp-99 and the substrate. Comparison of the enzyme-steroid complex
      in solution with the free enzyme in the crystalline state reveals similar
      differences between the positions of the helices.

PMID- 9778346
TI  - The preference of tryptophan for membrane interfaces.
AB  - One of the ubiquitous features of membrane proteins is the preference of
      tryptophan and tyrosine residues for membrane surfaces that presumably arises
      from enhanced stability due to distinct interfacial interactions. The physical
      basis for this preference is widely believed to arise from amphipathic
      interactions related to imino group hydrogen bonding and/or dipole interactions.
      We have examined these and other possibilities for tryptophan's interfacial
      preference by using 1H magic angle spinning (MAS) chemical shift measurements,
      two-dimensional (2D) nuclear Overhauser effect spectroscopy (2D-NOESY) 1H MAS
      NMR, and solid state 2H NMR to study the interactions of four tryptophan
      analogues with phosphatidylcholine membranes. We find that the analogues reside
      in the vicinity of the glycerol group where they all cause similar modest changes
      in acyl chain organization and that hydrocarbon penetration was not increased by
      reduction of hydrogen bonding or electric dipole interaction ability. These
      observations rule out simple amphipathic or dipolar interactions as the physical
      basis for the interfacial preference. More likely, the preference is dominated by
      tryptophan's flat rigid shape that limits access to the hydrocarbon core and its
      pi electronic structure and associated quadrupolar moment (aromaticity) that
      favor residing in the electrostatically complex interface environment.

PMID- 9778347
TI  - Thermodynamic parameters for an expanded nearest-neighbor model for formation of
      RNA duplexes with Watson-Crick base pairs.
AB  - Improved thermodynamic parameters for prediction of RNA duplex formation are
      derived from optical melting studies of 90 oligoribonucleotide duplexes
      containing only Watson-Crick base pairs. To test end or base composition effects,
      new sets of duplexes are included that have identical nearest neighbors, but
      different base compositions and therefore different ends. Duplexes with terminal
      GC pairs are more stable than duplexes with the same nearest neighbors but
      terminal AU pairs. Penalizing terminal AU base pairs by 0.45 kcal/mol relative to
      terminal GC base pairs significantly improves predictions of DeltaG degrees37
      from a nearest-neighbor model. A physical model is suggested in which the
      differential treatment of AU and GC ends accounts for the dependence of the total
      number of Watson-Crick hydrogen bonds on the base composition of a duplex. On
      average, the new parameters predict DeltaG degrees37, DeltaH degrees, DeltaS
      degrees, and TM within 3.2%, 6.0%, 6.8%, and 1.3 degreesC, respectively. These
      predictions are within the limit of the model, based on experimental results for
      duplexes predicted to have identical thermodynamic parameters.

PMID- 9778348
TI  - Crystal structures of a unique thermal-stable thymidylate synthase from Bacillus
      subtilis.
AB  - Unlike all other organisms studied to date, Bacillus subtilis expresses two
      different thymidylate synthases: bsTS-A and bsTS-B. bsTS-A displays enhanced
      enzymatic and structural thermal stability uncharacteristic of most TSs. Despite
      the high level of TS conservation across most species, bsTS-A shares low sequence
      identity (<40%) with the majority of TSs from other organisms. This TS and the
      TSs from Lactococcus lactis and phage Phi3T-to which it is most similar-have been
      of interest for some time since, by structure-based sequence alignment, they
      appear to lack several key residues shown by mutagenesis to be essential to
      enzymatic function [Greene, P. J., Yu, P. L., Zhao, J., Schiffer, C. A., and
      Santi, D. (1994) Protein Sci. 3, 1114-6]. In addition, bsTS-A demonstrates
      specific activity 2-3-fold higher than TS from Lactobacillus casei or Escherichia
      coli. We have solved the crystal structure of this unusual TS in four crystal
      forms to a maximum resolution of 1.7 A. Each of these crystal forms contains
      either one or two noncrystallographically related dimers. Stabilization of the
      beta-sheet dimer interface through a dramatic architecture of buttressed internal
      salt bridges maintains the structural integrity of bsTS-A at elevated
      temperatures. Melting curves of TSs from L. casei and E. coli are compared to
      that of TS-A from B. subtilis and correlated with numbers of hydrogen bonds, salt
      bridges, and the numbers of interactions localized to the dimer interface.
      Analysis of this structure will shed light on the conservation of function across
      diversity of sequence, as well as provide insights into the thermal stabilization
      of a highly conserved enzyme.

PMID- 9778349
TI  - Kinetic characterization of a bacteriophage T4 antimutator DNA polymerase.
AB  - Fidelity of DNA replication by bacteriophage T4 DNA polymerase is achieved in a
      multiplicative process: base selection by its polymerase activity and removal of
      misincorporated nucleotides by its exonuclease activity. The wild-type polymerase
      is capable of maintaining a balance between the two activities so that DNA
      replication fidelity is maximized without excessive waste of nucleotides.
      Antimutator enzymes exhibit a higher DNA replication fidelity than the wild-type
      enzyme, at the cost of increased nucleotide turnover. The antimutator A737V
      polymerase has been characterized kinetically using pre-steady-state and steady
      state methods to provide a kinetic sequence which defines the effect of the
      mutation on the discrete steps controlling DNA replication fidelity. Comparison
      of this sequence to that of the wild type [Capson, L. T., Peliska, J. A.,
      Kaboord, B. F., Frey, M. W., Lively, C., Dahlberg, M., and Benkovic, S. J. (1992)
      Biochemistry 31, 10984-10994] revealed that A737V polymerase differs in two ways.
      The rates at which DNA is transferred between the exonuclease and polymerase
      sites are reduced approximately 7-fold for a duplex DNA containing a mismatched
      3'-terminus, and the partitioning of the mismatched duplex between the polymerase
      and exonuclease sites is 1:2 versus 4:1 for the wild-type enzyme. The exonuclease
      activity of A737V relative to the wild-type enzyme is unchanged on single
      stranded DNA. However, the difference in partitioning the duplex DNA between the
      exonuclease and polymerase active sites results in an enhanced exonuclease
      activity for the antimutator enzyme.

PMID- 9778350
TI  - Single-turnover and pre-steady-state kinetics of the reaction of the adenine
      glycosylase MutY with mismatch-containing DNA substrates.
AB  - The DNA repair enzyme MutY plays an important role in the prevention of DNA
      mutations resulting from the presence of the oxidatively damaged lesion 7,8
      dihydro-8-oxo-2'-deoxyguanosine (OG) in DNA by the removal of misincorporated
      adenine residues in OG:A mispairs. MutY also exhibits adenine glycosylase
      activity toward adenine in G:A and C:A mismatches, although the importance of
      this activity in vivo has not been established. We have investigated the kinetic
      properties of MutY's glycosylase activity with OG:A and G:A containing DNA
      duplexes. Our results indicate that MutY's processing of these two substrates is
      distinctly different. By using single-turnover experiments, the intrinsic rate
      for adenine removal by MutY from an OG:A substrate was found to be at least 6
      fold faster than that from the corresponding G:A substrate. However, under
      conditions where [MutY] << [DNA], OG:A substrates are not quantitatively
      converted to product due to the inefficient turnover resulting from slow product
      release. In contrast, with a G:A substrate MutY's dissociation from the
      corresponding product is more facile, such that complete conversion of the
      substrate to product can be achieved under similar conditions. The kinetic
      results illustrate that the glycosylase reaction catalyzed by MutY has
      significant differences depending on the characteristics of the substrate. The
      lingering of MutY with the product of its reaction with OG:A mispairs may be
      biologically significant to prevent premature removal of OG. Thus, this approach
      is providing insight into factors that may be influencing the repair of damaged
      and mismatched DNA in vivo by base-excision repair glycosylases.

PMID- 9778351
TI  - A core folding model for catalysis by the hammerhead ribozyme accounts for its
      extraordinary sensitivity to abasic mutations.
AB  - Introducing abasic nucleotides at each of 13 positions in the conserved core of
      the hammerhead ribozyme causes a large decrease in the extent of catalysis
      [Peracchi, A., et al. (1996) Proc. Natl. Acad. Sci. U.S.A. 93, 11522]. This
      extreme sensitivity to structural defects is in contrast to the behavior of
      protein enzymes and larger ribozymes. Several additional differences in the
      behavior of the hammerhead relative to that of protein enzymes and larger
      ribozymes are described herein. The deleterious effects of the abasic mutations
      are not relieved by lowering the temperature, by increasing the concentration of
      monovalent or divalent metal ions, or by adding polyamines, in contrast to
      effects observed with protein enzymes and large RNA enzymes. In addition, the
      abasic mutations do not significantly weaken substrate binding. These results and
      previous observations are all accounted for by a "core folding" model in which
      the stable ground state structure of the hammerhead ribozyme complexed with the
      substrate is a partially folded state that must undergo an additional folding
      event to achieve its catalytic conformation. We propose that the peculiar
      behavior of the hammerhead arises because the limited structural interconnections
      in a small RNA enzyme do not allow the ground state to stably adopt the catalytic
      conformation; within the globally folded catalytic conformation, limited
      structural interconnections may further impair catalysis by hampering the precise
      alignment of active site functional groups. This behavior represents a basic
      manifestation of the well-recognized interconnection between folding and
      catalysis.

PMID- 9778352
TI  - Linker histones stabilize the intrinsic salt-dependent folding of nucleosomal
      arrays: mechanistic ramifications for higher-order chromatin folding.
AB  - Defined nucleosomal arrays reconstituted from core histone octamers and twelve
      208 bp tandem repeats of Lytechinus 5S rDNA (208-12 nucleosomal arrays) possess
      the ability to form an unstable folded species in MgCl2 whose extent of
      compaction equals that of canonical higher-order 30 nm diameter chromatin
      structures [Schwarz, P. M., and Hansen, J. C. (1994) J. Biol. Chem. 269, 16284
      16289]. To address the mechanistic functions of linker histones in chromatin
      condensation, purified histone H5 has been assembled with 208-12 nucleosomal
      arrays in 50 mM NaCl. Novel purification procedures subsequently were developed
      that yielded preparations of 208-12 chromatin model systems in which a majority
      of the sample contained both one histone octamer per 5S rDNA repeat and one
      molecule of histone H5 per histone octamer. The integrity of the purified 208-12
      chromatin has been extensively characterized under low-salt conditions using
      analytical ultracentrifugation, quantitative agarose gel electrophoresis,
      electron cryomicroscopy, and nuclease digestion. Results indicate that histone H5
      binding to 208-12 nucleosomal arrays constrains the entering and exiting linker
      DNA in a way that produces structures that are indistinguishable from native
      chicken erythrocyte chromatin. Folding experiments performed in NaC1 and MgC12
      have shown that H5 binding markedly stabilizes both the intermediate and
      extensively folded states of nucleosomal arrays without fundamentally altering
      the intrinsic nucleosomal array folding pathway. These results provide new
      insight into the mechanism of chromatin folding by demonstrating for the first
      time that distinctly different macromolecular determinants are required for
      formation and stabilization of higher-order chromatin structures.

PMID- 9778353
TI  - Characterization of the oligomeric states of RecA protein: monomeric RecA protein
      can form a nucleoprotein filament.
AB  - Self-assembly of RecA protein in solution and on single-stranded DNA exerts a
      significant effect on the catalytic activities of this protein. To manipulate the
      self-association reaction, we examined the effects of various salts on the self
      association of RecA from Thermus thermophilus (ttRecA) by circular dichroism
      spectroscopy and gel-filtration analysis. We showed that the self-association of
      ttRecA strongly depends on the kind and concentration of the salt, as well as on
      the protein concentration. Chaotropic ions were especially useful for obtaining
      RecA in its hexameric and monomeric states. On the basis of these observations,
      we were able to regulate the oligomeric states of ttRecA and we then examined the
      activity of RecA in various oligomeric states. Monomeric ttRecA bound to ssDNA
      and formed a nucleoprotein filament, which showed ssDNA-dependent ATPase
      activity. These results suggest that the monomeric form of RecA is an
      intermediate in filament formation on ssDNA.

PMID- 9778354
TI  - Laser light scattering evidence for a common wormlike growth structure of mixed
      micelles in bile salt- and straight-chain detergent-phosphatidylcholine aqueous
      systems: relevance to the micellar structure of bile.
AB  - We employed quasielastic and static light scattering to measure apparent values
      of the mean hydrodynamic radii (Rh)app, molecular weights (Mapp), and radii of
      gyration (Rg)app in solutions containing mixed micelles composed of bile salts
      (cholate and taurochenodeoxycholate, both cholanoyl derivatives) and the
      glycoacyl chain detergent, octyl glucoside, with egg yolk phosphatidylcholine
      (EYPC) as functions of total lipid concentration (0.1-10 g/dL), EYPC/detergent
      molar ratio (0-1.2), and ionic strength (0.15-0.4 M NaCl) at 20 degreesC and 1
      atm. As the mixed micellar phase boundaries were approached by dilution, (Rh)app,
      Mapp, and (Rg)app values increased markedly by up to 20-fold. For each micellar
      system, the scaling ratios (Rh)app/Mapp1/2 and (Rg)app/(Rh)app remained
      essentially constant at 0.018 nm/(g/mol)1/2 and 1.5 (dimensionless),
      respectively, despite large variations in total lipid concentration, detergent
      molecular species, and ionic strength. Refined data analysis is inconsistent with
      a flat "mixed-disc" model for bile salt-EYPC micelles [Mazer, N. A., Benedek, G.
      B., and Carey, M. C. (1980) Biochemistry 19, 601] and octyl glucoside-EYPC
      micelles principally because the numerical value of (Rh)app/Mapp1/2 corresponds
      to a hypothetical disk thickness of approximately 1 nm, which is 4-fold smaller
      than the bimolecular width of EYPC molecules, and for a disk, (Rg)app/(Rh)app
      ratios should be close to 1 at low total lipid concentrations. Assuming disc
      shaped micelles, we show that intermicellar excluded volume interactions would
      have only a minor effect on Mapp and cannot account for the unrealistic disk
      thickness. Instead, locally cylindrical, semiflexible wormlike micelles of
      diameter d = 4 nm and persistence length xip = 17 nm in solution are compatible
      with the observed (Rh)app/Mapp1/2 and (Rg)app/(Rh)app values when intermicellar
      excluded-volume interactions are considered. With EYPC/taurochenodeoxycholate =
      0.6 and EYPC/cholate = 1.0 in 0.15 M NaCl, independent micelles grow upon
      dilution and use of the second virial coefficient [Egelhaaf, S. U., and
      Schurtenberger, P. (1994) J. Phys. Chem. 98, 8560] is adequate for estimating
      micellar weights. The systems EYPC/cholate = 1.0 in 0.4 M NaCl, EYPC/cholate =
      1.2 in 0.15 M NaCl, and EYPC/octyl glucoside = 0.13 in 0.15 M NaCl all form
      highly overlapping, semidilute polymer solutions, which mimic the observed
      scaling ratios. In such semidilute systems, use of the second virial coefficient
      alone to account for intermicellar interactions is inadequate for estimating
      micellar weights. The results of the present study, in combination with locations
      of known phase boundaries of the ternary bile salt-EYPC-water phase diagram at
      high dilution, suggest that elongation, as well as entanglement of wormlike mixed
      micelles may occur at concentrations approaching the micellar phase limit.

PMID- 9778355
TI  - Secondary structure of the exchange-resistant core from the nicotinic
      acetylcholine receptor probed directly by infrared spectroscopy and
      hydrogen/deuterium exchange.
AB  - The spectral changes that occur in infrared spectra recorded as a function of
      time after exposure of the nicotinic acetylcholine receptor (nAChR) to 2H2O
      buffer were examined in order to investigate the secondary structure of the
      transmembrane domain. The resolution-enhanced amide I band in spectra recorded
      during the first 12 h after exposure to 2H2O exhibits subtle downshifts in
      frequency of alpha-helical and beta-sheet vibrations. A strong intensity of the
      unexchanged alpha-helical vibration near 1655 cm-1 after 3 days exposure to 2H2O
      suggests that a large proportion of the remaining 25% of unexchanged peptide
      hydrogens adopts an alpha-helical conformation. Further exposure of the nAChR to
      2H2O under conditions of both increasing pH and membrane "fluidity" led to
      additional exchange of peptide hydrogens for deuterium. The greatest degree of
      peptide 1H/2H exchange (95%) under nondenaturing conditions was found for the
      nAChR reconstituted into the highly fluid egg phosphatidylcholine membranes
      lacking cholesterol and anionic lipids at pH 9.0. This enhanced exchange was
      accompanied by a decrease in intensity near 1655 cm-1 due to the downshift in
      frequency of peptides in the alpha-helical conformation, whereas no clear
      evidence was found for the further exchange of beta-sheet. Some unexchanged alpha
      helical peptide hydrogens were still observed. As the exchange-resistant peptides
      likely include those found within the hydrophobic environment of the lipid
      bilayer, these data strongly support an alpha-helical secondary structure of the
      transmembrane domain.

PMID- 9778356
TI  - Identification of phosphorylation sites on AChR delta-subunit associated with
      dispersal of AChR clusters on the surface of muscle cells.
AB  - The innervation of embryonic skeletal muscle cells is marked by the
      redistribution of nicotinic acetylcholine receptors (AChRs) on muscle surface
      membranes into high-density patches at nerve-muscle contacts. To investigate the
      role of protein phosphorylation pathways in the regulation of AChR surface
      distribution, we have identified the sites on AChR delta-subunits that undergo
      phosphorylation associated with AChR cluster dispersal in cultured myotubes. We
      found that PKC-catalyzed AChR phosphorylation is targeted to Ser378, Ser393, and
      Ser450, all located in the major intracellular domain of the AChR delta-subunit.
      Adjacent to one of these sites is a PKA consensus target site (Ser377) that was
      efficiently phosphorylated by purified PKA in vitro. The PKC activator 12-O
      tetradecanoylphorbol-13-acetate (TPA) and the phosphoprotein phosphatase
      inhibitor okadaic acid (OA) produced increased phosphorylation of AChR delta
      subunits on the three serine residues that were phosphorylated by purified PKC in
      vitro. In contrast, treatment of these cells with the PKA activator forskolin, or
      with the cell-permeable cAMP analogue 8-bromo-cAMP, did not alter the
      phosphorylation state of surface AChR, suggesting that PKA does not actively
      phosphorylate the delta-subunit in intact chick myotubes. The effects of TPA and
      OA included an increase in the proportion of surface AChR that is extracted in
      Triton X-100, as well as the spreading of AChR from cluster regions to adjacent
      areas of the muscle cell surface. These findings suggest that PKC-catalyzed
      phosphorylation on the identified serine residues of AChR delta-subunits may play
      a role in the surface distribution of these receptors.

PMID- 9778357
TI  - Transbilayer movement of NBD-labeled phospholipids in red blood cell membranes:
      outward-directed transport by the multidrug resistance protein 1 (MRP1).
AB  - The outward movement (flop) of fluorescently labeled analogues of
      phosphatidylserine (PS) and phosphatidylcholine (PC) in human and murine red
      blood cells (RBC) was examined. 1-Oleoyl-2-[6(7-nitrobenz-2-oxa-1,3-diazol-4
      yl)amino]caproyl (C6-NBD) analogues of PS and PC were incorporated in the inner
      leaflet of the plasma membrane through the action of aminophospholipid
      translocase or through equilibration upon prolonged incubation, respectively.
      After removal of noninternalized probe, externalization of C6-NBD-PS or C6-NBD-PC
      from the inner to outer leaflet was monitored by continuous incubation of the
      cells in the presence of bovine serum albumin. Flop rates for both probes in
      intact human RBC were virtually identical (t1/2 approximately 1.5 h), confirming
      earlier findings by Bitbol et al. [Bitbol, M., et al. (1988) Proc. Natl. Acad.
      Sci. U.S.A. 85, 6783-6787] and Connor et al. [Connor, J., et al. (1992) J. Biol.
      Chem. 267, 19412-19417]. Flop activity in resealed RBC ghosts could only be found
      upon coinclusion of both ATP and oxidized glutathione (GSSG). Furthermore, flop
      in intact cells was sensitive to verapamil (IC50 = 5-7 microM), vincristine (IC50
      = 20 microM), and indomethacin (IC50 = 50 microM), suggesting the involvement of
      proteins conferring multidrug resistance (MDR). Experiments with RBC from knock
      out mice for multidrug resistance P-glycoproteins (Mdr1a/1b-/- and Mdr2-/-) and
      multidrug resistance protein 1 (Mrp1-/-) revealed that Mrp1 is responsible for
      the observed flop of the fluorescent lipid analogues. We found no indications for
      outward transport of endogenous PS by any of these drug-transporting proteins as
      measured by a sensitive prothrombinase assay. Neither aminophospholipid
      translocase nor Ca2+-induced lipid scramblase activities were affected in RBC of
      these knock-out mice. We conclude that lipid floppase activity, as detected with
      lipid probes, reflects the activity of MRP1 recognizing the modified lipid
      analogues as xenobiotics to be expelled from the cell.

PMID- 9778358
TI  - Posttranslational modifications of the C-terminus of alpha-tubulin in adult rat
      brain: alpha 4 is glutamylated at two residues.
AB  - In adult mammalian brain, the C-terminus of alpha-tubulin exhibits a high degree
      of polymorphism due to a combination of four covalent posttranslational
      modifications: glutamylation, tyrosination, detyrosination, and removal of the
      penultimate glutamate residue (C-terminal deglutamylation). Glutamylation is the
      most abundant. To characterize the glutamylation of alpha-tubulin and its
      relationship with the other modifications, we developed a chromatographic
      procedure for purifying alpha-tubulin C-terminal peptides. The purified peptides
      were identified by matrix-assisted laser desorption ionization time-of-flight
      mass spectrometry (MALDI-TOF) and amino acid sequencing. In this report, we
      provide a complete description of the glutamylation of tyrosinated,
      detyrosinated, and C-terminal deglutamylated isoforms of both alpha-tubulin
      isotypes (alpha1/2 and alpha4) expressed in adult rat brain. In particular, we
      describe for the first time the glutamylation of alpha4. More than 90% of the
      alpha-tubulin is glutamylated, and more than 75% of it is nontyrosinated. alpha4
      is more extensively glutamylated than alpha1/2, containing as many as 11
      posttranslationally added glutamate residues. The most abundant alpha4 isoform is
      nontyrosinated, containing five posttranslationally added glutamates, whereas the
      most abundant alpha1/2 isoforms are nontyrosinated, with only one or two
      posttranslationally added glutamates. In contrast to alpha1/2, alpha4 is
      glutamylated at two separate residues (Glu-443 and Glu-445) in the sequence
      431DYEEVGIDSYEDEDEGEE448. This is the first evidence that glutamylation can occur
      on two different residues in the same mammalian tubulin isotype.

PMID- 9778359
TI  - N-Linked glycosylation is essential for the functional expression of the
      recombinant P2X2 receptor.
AB  - P2X receptors are integral membrane proteins that belong to the growing family of
      transmitter-gated ion channels. The extracellular domain of these receptors
      contains several consensus sequences for N-linked glycosylation that may
      contribute to the functional expression of the channel. We have previously
      reported the extracellular orientation of asparagine residues 182, 239, and 298
      of the P2X2 receptor subunit by showing that the protein is glycosylated at each
      site [Torres, G. E., et al. (1998) FEBS Lett. 425, 19-23 (1)]. In this study, we
      focused on the consequences of removing N-linked glycosylation from the P2X2
      receptor by using two different approaches, tunicamycin treatment or site
      directed mutagenesis. HEK-293 cells stably transfected with the P2X2 receptor
      subunit showed little or no response to ATP after tunicamycin treatment. In
      addition, loss of function was observed with the elimination of all three N
      linked glycosylation sites from P2X2. Cell surface labeling with biotin or
      indirect immunofluorescence revealed that the expression of the nonglycosylated
      receptors produced by either tunicamycin or site-directed mutagenesis is greatly
      reduced at the cell surface, indicating that the nonglycosylated P2X2 receptors
      are retained inside the cell. These data provide the first direct evidence for a
      critical role of N-linked glycosylation in the cell surface expression of a P2X
      receptor subunit.

PMID- 9778361
TI  - Change in conformation of plasma membrane phospholipid scramblase induced by
      occupancy of its Ca2+ binding site.
AB  - Phospholipid (PL) scramblase is a 35.1 kDa plasma membrane protein that mediates
      the accelerated transbilayer migration of plasma membrane PL in activated,
      injured, or apoptotic cells exposed to elevated intracellular Ca2+. We recently
      identified a conserved segment in the PL scramblase polypeptide (residues Asp273
      to Asp284) that is essential for its PL-mobilizing function and was presumed to
      contain the Ca2+ binding site of the protein (Zhou, Q., Sims, P. J., and Wiedmer,
      T. (1998) Biochemistry 37, 2356-2360). Whereas the sequence of this peptide
      segment resembles that of known Ca2+-binding loops within EF-hand containing
      proteins, it is unusual in being a single such loop in the entire protein and in
      being closely spaced to the predicted transmembrane helix (Ala291-Gly309). To
      gain insight into how Ca2+ activates the PL-mobilizing function of PL scramblase,
      we analyzed conformational changes associated with occupancy of this putative
      Ca2+ binding site. In addition to activation by Ca2+, the PL-mobilizing function
      of PL scramblase was found to be activated by other ions, with apparent
      affinities Tb3+, La3+ >> Ca2+ > Mn2+ > Zn2+ > Sr2+ >> Ba2+, Mg2+. Evidence for
      coordinate binding of metal ion by the polypeptide was provided by resonance
      energy transfer from protein Trp to Tb3+, which was competed by excess Ca2+.
      Metal binding to PL scramblase was accompanied by increased right-angle light
      scattering and by a prominent change in circular dichroism, suggesting that
      coordinate binding of the metal ion induces a conformational change that includes
      self-aggregation of the polypeptide. Consistent with this interpretation,
      addition of Ca2+ was found to protect PL scramblase from proteolysis by trypsin
      both in detergent solution as well as in situ, within the erythrocyte membrane.
      Mutation in the segment Asp273-Asp284 reduced Tb3+ incorporation and attenuated
      the change in CD spectrum induced by bound metal ligand, confirming that this
      suspected EF-hand loopike segment of the polypeptide directly contributes to the
      Ca2+ binding site.

PMID- 9778360
TI  - Conformational changes in the cytoplasmic domain of the Escherichia coli
      aspartate receptor upon adaptive methylation.
AB  - By using targeted disulfide cross-linking, we have characterized structural
      changes that the Escherichia coli aspartate receptor undergoes upon modification
      of the four specific residues that are reversibly methylated during sensory
      adaptation. Cysteine residues were introduced at specific positions either in the
      cytoplasmic domain or in the periplasmic domain, and the rates of disulfide cross
      linking were used to probe for conformational changes upon covalent modification.
      Conversion of the methylation sites from glutamates to glutamines greatly reduced
      the rate of disulfide formation between residues 265 and 265' and residues 250
      and 250' in the cytoplasmic domain but not between residues 36 and 36' in the
      periplasmic domain. (Primes are used to indicate the second of the two identical
      subunits in the homologous dimer.) The covalent modification of the cytoplasmic
      domain induces conformational changes that are detectable in the cytoplasmic
      domain but none that are detectable in the periplasmic domain.

PMID- 9778362
TI  - A snake toxin inhibitor of inward rectifier potassium channel ROMK1.
AB  - Mamba snake dendrotoxins have been used extensively in biochemical and
      physiological studies of K+ channels of the brain. Their known targets of
      inhibition have been limited to the family of voltage-gated K+ channels. We
      report the isolation of a dendrotoxin inhibitor of ROMK1, a channel belonging to
      the inward rectifier family of K+ channels. The inhibitory activity, fractionated
      to purity with FPLC and HPLC, is identical to a previously identified delta
      dendrotoxin. To verify that delta-dendrotoxin blocks ROMK1 channels, a cDNA
      encoding the toxin was synthesized and recombinant toxin expressed in Escherichia
      coli. Electrophysiological recordings reveal that recombinant delta-dendrotoxin
      has a half-maximal inhibition constant (Kd) of 150 nM when applied to ROMK1
      channels expressed in Xenopus laevis oocytes. That the delta-dendrotoxin binding
      site exists on separate K+ channel classes is shown by its high affinity for two
      of the voltage-gated family of channels, Kv1.1 (Kd < 0.1 nM) and Kv1.6 (Kd = 23
      nM). Single amino acid substitutions in ROMK1 indicate that delta-dendrotoxin
      binds to the pore region of ROMK1 even though it does not completely block
      conduction through the pore. These results suggest that dendrotoxins inhibit K+
      channels by recognizing the structurally conserved pore region of these channels.

PMID- 9778363
TI  - The effect of pressure on the bacteriochlorophyll a binding sites of the core
      antenna complex from Rhodospirillum rubrum.
AB  - In this paper we examine the effect of pressure on the absorption spectrum and
      binding site of the core antenna complex from the photosynthetic bacterium
      Rhodospirillum rubrum. Absorption spectra and Raman spectra in preresonance with
      the Qy transition of the bacteriochlorophyll a were studied at pressures up to
      625 MPa. In agreement with previous work we observe a pressure-induced red shift
      and broadening of the absorption spectrum. We show that at these pressures the
      pigments within the protein matrix at room temperature experience little if any
      distortion, and the hydrogen-bonding network involving the C2 and C9 carbonyl
      groups of the pigment molecules are undisturbed. Having shown the lack of
      sensitivity to pressure of the binding site interactions, which are known to
      modulate the absorption spectrum, we feel that it is relatively safe to attribute
      the pressure-induced red shift broadly to solvatochromic effects and, in
      particular, to the modulation of the pigment-pigment interactions by the
      pressure. This paper represents the first vibrational study of photosynthetic
      complexes at high pressure and the first application of FT Raman spectroscopy to
      biological molecules at high pressure.

PMID- 9778364
TI  - Ligand binding is the principal determinant of stability for the p21(H)-ras
      protein.
AB  - p21(H-ras) is a 21 kDa, alpha/beta sheet protein that, as a member of the GTPase
      superfamily, acts as a molecular switch in signal transduction pathways. The
      essential role of GDP and Mg2+ in maintaining the inactive conformation of p21(H
      ras) prompted a study of the influence of these ligands on its structure and
      stability. The urea-induced equilibrium unfolding transitions for the ternary
      (p21.GDP.Mg2+), binary (p21.GDP) and apo (p21) forms of p21(H-ras) at pH 7.5 and
      25 degreesC were monitored by absorbance and circular dichroism spectroscopies.
      The cooperative disruptions of the secondary and tertiary structures for all
      three forms are well-described by a two-state model. Global analysis of the
      equilibrium unfolding data yields a free energy of folding in the absence of urea
      and under standard state conditions of 14.1 +/- 0.2 kcal mol-1, 7.5 +/- 0.4 kcal
      mol-1 and 1.8 +/- 0.2 kcal mol-1 for ternary, binary and apo forms, respectively.
      Near- and far-UV circular dichroism spectra of these three forms of p21(H-ras)
      show that removal of the Mg2+ from the ternary complex loosens the aromatic side
      chain packing but leaves the secondary structure largely unchanged. The removal
      of both GDP and Mg2+ completely releases the side chain packing but leaves a
      substantial fraction of the secondary structure intact. These results demonstrate
      that ligands play a significant role in the stability and structure of the
      p21.GDP.Mg2+ complex. The amino acid sequence itself only contains sufficient
      information to direct the formation of a large portion of the secondary structure
      in a molten globule-like state. Ligand binding is required to drive the formation
      of specific tertiary structure.

PMID- 9778365
TI  - The role of ligand binding in the kinetic folding mechanism of human p21(H-ras)
      protein.
AB  - p21(H-ras) plays a critical role in signal transduction pathways by cycling
      between an active, GTP/Mg2+ ternary complex and an inactive, GDP/Mg2+ complex.
      Urea-induced equilibrium unfolding studies [Zhang and Matthews (1998)
      Biochemistry 37, 14881-14890] have shown that GDP and Mg2+ play essential roles
      in stabilizing the protein. To probe the mechanism of folding and to examine the
      effects of these ligands on the kinetic folding reaction, unfolding and refolding
      experiments were performed at a variety of urea and ligand concentrations. A
      burst phase intermediate with substantial secondary structure and marginal
      stability was observed during refolding by stopped-flow circular dichroism
      spectroscopy. Three subsequent refolding phases were detected using a combination
      of absorbance, circular dichroism, and fluorescence spectroscopy. The fastest
      phase involves ligand binding and appears to directly form the fully folded
      enzyme. The intermediate and slow phases do not depend on either urea or ligand
      concentration under strongly refolding conditions and appear to reflect
      isomerization or rearrangement reactions. Double- jump experiments demonstrated
      that the intermediate and slow refolding phases both lead to the native
      conformation and correspond to parallel rather than sequential reactions.
      Unfolding is controlled by two phases that involve the release of the ligands
      when the ligands are in excess. At stoichiometric ligand concentrations, however,
      the rate-limiting steps in unfolding change from ligand release to isomerization
      or rearrangement reactions at high urea concentrations. Only the faster unfolding
      reaction is observed in the absence of Mg2+, suggesting that this reaction
      corresponds to the unfolding of the binary complex, p21(H-ras)*GDP. The slower
      unfolding reaction presumably corresponds to the unfolding of the ternary
      complex, p21(H-ras)*GDP. Mg2+. The kinetic data show that the refolding/unfolding
      of p21(H-ras) occurs through parallel channels that are strongly influenced by
      the binding/release of GDP and Mg2+ to/from a pair of native conformers.

PMID- 9778366
TI  - Triplet properties and interactions of the primary electron donor and antenna
      chromophores in membranes of Heliobacterium chlorum, studied with ADMR
      spectroscopy.
AB  - The triplet states of antenna and reaction center bacteriochlorophyll (BChl) g in
      membranes of Heliobacterium chlorum were studied by optically detected magnetic
      resonance in zero magnetic field, using absorbance detection. A variety of
      triplet states was detected, which were all localized on single BChl g
      chromophores as concluded from a comparison with the triplet state of monomeric
      BChl g in organic solvents. With the aid of the microwave-induced absorbance
      difference spectra, we assign a triplet state with zero-field splitting
      parameters |D| = 727.5 and |E| = 254. 5 MHz to that of the primary donor. The low
      |E| value indicates that the BChls of the primary donor are monoligated. The
      intensities of the zero-field transitions were strongly dependent on the redox
      state of the secondary electron acceptors. A triplet state with |D| = 690-705 MHz
      and |E| =230 MHz, present under all redox conditions, is associated with antenna
      BChl g absorbing at 814 nm. Its triplet yield was independent of the redox
      conditions; we conclude therefore that the antenna chromophores absorbing at 814
      nm are not connected with the reaction center at cryogenic temperatures (1.2 K).
      In addition, relatively strong signals were detected belonging to triplet states
      with |D| and |E| of 663-680 and 220-227 MHz, respectively, whose amplitudes were
      dependent on the redox conditions. Triplet states with these zero-field splitting
      parameters are located on antenna chromophores absorbing between 798-814 nm;
      their zero-field transitions and absorbance difference spectra indicate a
      considerable heterogeneity. The concentration of triplet states of antenna
      chromophores absorbing around 800 nm decreased markedly upon prolonged excitation
      at 1.2 K. This phenomenon is attributed to quenching of excitations on antenna
      pigments by stable charge separation in the closely connected reaction center,
      possibly involving a low-quantum yield menaquinone electron acceptor.

PMID- 9778367
TI  - Single electron reduction of cytochrome c oxidase compound F: resolution of
      partial steps by transient spectroscopy.
AB  - The final step of the catalytic cycle of cytochrome oxidase, the reduction of
      oxyferryl heme a3 in compound F, was investigated using a binuclear polypyridine
      ruthenium complex (Ru2C) as a photoactive reducing agent. The net charge of +4 on
      Ru2C allows it to bind electrostatically near CuA in subunit II of cytochrome
      oxidase. Photoexcitation of Ru2C with a laser flash results in formation of a
      metal-to-ligand charge-transfer excited state, Ru2C, which rapidly transfers an
      electron to CuA of cytochrome oxidase from either beef heart or Rhodobacter
      sphaeroides. This is followed by reversible electron transfer from CuA to heme a
      with forward and reverse rate constants of k1 = 9.3 x 10(4) s-1 and k-1 = 1.7 x
      10(4) s-1 for R. sphaeroides cytochrome oxidase in the resting state. Compound F
      was prepared by treating the resting enzyme with excess hydrogen peroxide. The
      value of the rate constant k1 is the same in compound F where heme a3 is in the
      oxyferryl form as in the resting enzyme where heme a3 is ferric. Reduction of
      heme a in compound F is followed by electron transfer from heme a to oxyferryl
      heme a3 with a rate constant of 700 s-1, as indicated by transients at 605 and
      580 nm. No delay between heme a reoxidation and oxyferryl heme a3 reduction is
      observed, showing that no electron-transfer intermediates, such as reduced CuB,
      accumulate in this process. The rate constant for electron transfer from heme a
      to oxyferryl heme a3 was measured in beef cytochrome oxidase from pH 7.0 to pH
      9.5, and found to decrease upon titration of a group with a pKa of 9.0. The rate
      constant is slower in D2O than in H2O by a factor of 4.3, indicating that the
      electron-transfer reaction is rate-limited by a proton-transfer step. The pH
      dependence and deuterium isotope effect for reduction of isolated compound F are
      comparable to that observed during reaction of the reduced, CO-inhibited CcO with
      oxygen by the flow-flash technique. This result indicates that electron transfer
      from heme a to oxyferryl heme a3 is not controlled by conformational effects
      imposed by the initial redox state of the enzyme. The rate constant for electron
      transfer from heme a to oxyferryl heme a3 is the same in the R. sphaeroides K362M
      CcO mutant as in wild-type CcO, indicating that the K-channel is not involved in
      proton uptake during reduction of compound F.

PMID- 9778369
TI  - Effects of L-histidine and its structural analogues on human N
      myristoyltransferase activity and importance of EEVEH amino acid sequence for
      enzyme activity.
AB  - Myristoyl-CoA:protein N-myristoyltransferase (NMT) is an essential eukaryotic
      enzyme that catalyzes the cotranslational transfer of myristate to the NH2
      terminal glycine residue of a number of important proteins of diverse function.
      Human NMT (hNMT) activity was found to be activated by L-histidine in a
      concentration-dependent manner. In contrast, two structural analogues of L
      histidine, L-histidinol and histamine, inhibited hNMT activity in a
      noncompetitive manner with half-maximal inhibitions of 18 and 1.5 mM,
      respectively. The inhibition of hNMT activity by L-histidinol was reversed by a 2
      fold molar excess of L-histidine, suggesting that L-histidine and L-histidinol
      were competing for a common site on NMT. Kinetic data indicated that whereas L
      histidine enhanced the Vmax, both L-histidinol and histamine decreased the Vmax;
      none of these compounds altered the Km. Our studies suggest that L-histidine and
      its analogues may be interacting with His-293, involved in myristoyl-CoA
      transfer, rather than His-218, and implicated in the transfer of myristoyl-CoA to
      the peptide substrates. Site-directed mutagenesis of His-293, Val-291, and Glu
      290 resulted in proteins with no measurable NMT activity. The most conserved
      region in the catalytic domain EEVEH (289-293) is critical for the myristoyl-CoA
      transfer in the NMT-catalyzed reactions. This region will be useful for the
      design of regulators of NMT function.

PMID- 9778368
TI  - Definition of the redox states of cobalt-precorrinoids: investigation of the
      substrate and redox specificity of CbiL from Salmonella typhimurium.
AB  - The enzyme CbiL from the facultative anaerobe Salmonella typhimurium exhibits a
      high degree of homology to CobI from the aerobe Pseudomonas denitrificans (29%
      identity; 51% conservation obtained by a Blastp search of the ncbi database). As
      CobI catalyzes the third methylation in the aerobic pathway to vitamin B12 it is
      proposed that CbiL catalyzes the analogous step in the anaerobic pathway.
      Potential metallo and metal-free substrates were characterized and their redox
      states defined by a combination of physicochemical techniques (MALDI-MS, NMR,
      UV/vis, IR, and EPR) and then used to investigate the function of CbiL. CbiL
      exhibited an absolute requirement for the presence of a metal ion (Co(II),
      Ni(II), or Zn(II)) within the tetrapyrrole substrate. CbiL had no preference for
      the redox state of its cobalt tetrapyrrole substrate, methylating both the
      reduced form, Co(II) 2, 7-dimethyl-dipyrrocorphin (Co(II)-precorrin-2), and the
      oxidized form, Co(III) 2,7-dimethyl-isobacterioclorin (Co(III)-factor-II). In
      contrast CbiL had a marked preference for the oxidized Ni(II) and Zn(II)-2,7
      dimethyl-isobacteriochlorin (Ni(II) and Zn(II)-factor-II). Removal of the metal
      ion from a product of CbiL (Zn(II)-factor-III) allowed characterization by 13C
      NMR, identifying the tetrapyrrole as 2,7,20-trimethyl-isobacteriochlorin (factor
      3), indicating that CbiL methylates at C20, the same site as that methylated by
      CobI. Competition experiments, utilizing isotopic labeling to distinguish
      otherwise identical mass substrates and products, revealed that oxidized Co(III)
      or Ni(II)-factor-II were equally good substrates, whereas Co(II)-precorrin-2 was
      much preferred over Ni(II)-precorrin-2. Excess Ni(II)-precorrin-2 did not
      decrease CbiL methylation of Co(II)-precorrin-2, implying that CbiL has a low
      affinity for Ni(II)-precorrin-2. These results are interpreted on the basis of
      tetrapyrrole ruffling occurring on the optimization of the metallo-N bond
      distances. The greater flexibility of the reduced precorrin-2 ring system allows
      greater deformation on accommodating the bound metal ion, the distortions imposed
      by bound Ni(II) or Zn(II) ions being larger than Co(II). The resulting
      distortions imposed on the precorrin ring could then decrease catalysis by
      causing a departure from the optimal substrate conformation required for CbiL. On
      oxidation of the Ni(II) or Zn(II)-precorrin-2, the increased stiffness of the
      ring could then constrain the metallo-factor-II conformation toward that of the
      usual substrate, allowing greater methylation by CbiL. In contrast to its
      counterpart CobI in the aerobic pathway of B12 biosynthesis, which methylates the
      metal-free precorrin-2, these studies show CbiL to be the first methylase unique
      to the anaerobic pathway, methylating a metallo-precorrin-2 substrate.
      Implications of CbiL specificity for the mechanism of the anaerobic B12 pathway
      are discussed.

PMID- 9778370
TI  - Characterization of the macrolide P-450 hydroxylase from Streptomyces venezuelae
      which converts narbomycin to picromycin.
AB  - The post-polyketide synthase (PKS) biosynthetic tailoring of macrolide
      antibiotics usually involves one or more oxidation reactions catalyzed by
      cytochrome P450 monooxygenases. As the specificities of members from this class
      of enzymes vary significantly among PKS gene clusters, the identification and
      study of new macrolide P450s are important to the growing field of combinatorial
      biosynthesis. We have isolated the cytochrome P450 gene picK from Streptomyces
      venezuelae which is responsible for the C-12 hydroxylation of narbomycin to
      picromycin. The gene was located by searching regions proximal to modular PKS
      genes with a probe for macrolide P450 monooxygenases. The overproduction of PicK
      with a C-terminal six-His affinity tag (PicK/6-His) in Escherichia coli aided the
      purification of the enzyme for kinetic analysis. PicK/6-His was shown to catalyze
      the in vitro C-12 hydroxylation of narbomycin with a kcat of 1.4 s-1, which is
      similar to the value reported for the related C-12 hydroxylation of erythromycin
      D by the EryK hydroxylase. The unique specificity of this enzyme should be useful
      for the modification of novel macrolide substrates similar to narbomycin, in
      particular, ketolides, a promising class of semisynthetic macrolides with
      activity against erythromycin-resistant pathogens.

PMID- 9778371
TI  - Carbon-13 isotope effect studies of Trypanosoma brucei ornithine decarboxylase.
AB  - Carbon isotope effect studies were undertaken with the wild-type pyridoxal 5'
      phosphate (PLP)-dependent enzyme ornithine decarboxylase (ODC) from Trypanosoma
      brucei and with several active site mutants of the enzyme. For the
      decarboxylation of the optimal substrate, L-ornithine, by wild-type ODC, the
      observed carbon isotope effect (k12/k13) is 1.033 at pH 7.3. In comparison to the
      expected intrinsic isotope effect (k12/k13 = 1.06) for decarboxylation, this
      value suggests that both the rate of decarboxylation and the rate of Schiff base
      interchange with L-ornithine are partially rate-limiting for the reaction steps
      up to decarboxylation. In contrast, with the alternate substrate L-Lys, which
      shows lower catalytic efficiency, the carbon isotope effect increased to 1.063,
      demonstrating that decarboxylation has become the rate-limiting step. For the
      mutant enzymes, E274A ODC and C360A ODC, with L-ornithine as substrate the carbon
      isotope effect also approaches the intrinsic limit. Glu-274 was previously
      demonstrated to play a direct role in carbanion stabilization, and thus the large
      carbon isotope effect (k12/k13 = 1.055) is consistent with an impaired rate of
      decarboxylation compared to wild-type ODC. In contrast, for K69A ODC, the isotope
      effect is almost entirely suppressed, suggesting that Schiff-base formation
      (which now must occur from enzyme-bound PLP, rather than from an enzyme-bound PLP
      Schiff base) has become rate-determining.

PMID- 9778372
TI  - Thiol ester hydrolysis catalyzed by glutathione S-transferase A1-1.
AB  - rGSTA1-1 has been shown to catalyze the hydrolysis of the thiol ester
      glutathionyl ethacrynate (E-SG). In contrast, neither the retro-Michael addition
      with the substrate EA-SG, to yield GSH and ethacrynic acid (EA), nor the
      conjugation reaction between GSH and EA to yield the thiol ester E-SG was
      catalyzed to any measurable extent under similar conditions. The steady state
      kcat and KM for hydrolysis of E-SG by wild type rGSTA1-1 were 0.11 +/- 0.009 min
      1 and 15.7 +/- 1.6 mM, respectively. The site-directed mutant, Y9F, in which the
      catalytic Tyr-9 is substituted with Phe, was completely inactive in this
      reaction. To uncover a mechanistic signature that would distinguish between
      direct hydrolysis and covalent catalysis involving acylation of Tyr-9, solvent
      isotope exchange and mass spectrometry experiments were performed. No 18O
      incorporation into the starting thiol ester was detected with initial velocity
      solvent isotope exchange experiments. However, covalent adducts corresponding to
      acylated protein also were not observed by electrospray ionization mass
      spectrometry, even with an assay that minimized the experimental dead time and
      which allowed for detection of N-acetyltyrosine acylated with EA in a chemical
      model system. The kon and koff rate constants for association and dissociation of
      E-SG were determined, by stopped flow fluorescence, to be 5 x 10(5) s-1 M-1 and
      6.7 s-1, respectively. Together with the isotope partitioning results, these rate
      constants were used to construct partial free energy profiles for the GST
      catalyzed hydrolysis of E-SG, assuming that Tyr-9 acts as a general acid-base
      catalyst. The "one-way flux" of the thiol esterase reaction results directly from
      the thermodynamic stability of the products after rate-limiting attack of the
      thiol ester by H2O or Tyr-9, and is sufficient to drive the hydrolysis to
      completion, in contrast to GST-catalyzed breakdown of other GSH conjugates.

PMID- 9778373
TI  - Processing of the Alzheimer's disease amyloid precursor protein in Pichia
      pastoris: immunodetection of alpha-, beta-, and gamma-secretase products.
AB  - betaA4 (Abeta) amyloid peptide, a major component of Alzheimer's disease (AD)
      plaques, is a proteolytic product of the amyloid precursor protein (APP).
      Endoproteases, termed beta- and gamma-secretase, release respectively the N- and
      C-termini of the peptide. APP default secretion involves cleavage within the
      betaA4 domain by alpha-secretase. To study the conservation of APP processing in
      lower eukaryotes, the yeast Pichia pastoris was transfected with human APP695
      cDNA. In addition to the full-length integral transmembrane protein found in the
      cell lysate, soluble/secreted APP (sAPP) was detected in the culture medium. Most
      sAPP comprised the N-terminal moiety of betaA4 and corresponds to sAPPalpha, the
      product of alpha-secretase. The culture medium also contained minor secreted
      forms detected by a monoclonal antibody specific for sAPPbeta (the ectodomain
      released by beta-secretase cleavage). Analysis of the cell lysates with specific
      antibodies also detected membrane-associated C-terminal fragments corresponding
      to the products of alpha and beta cleavages. Moreover, immunoprecipitation of the
      culture medium with three antibodies directed at distinct epitopes of the betaA4
      domain yielded a 4 kDa product with the same electrophoretic mobility as betaA4
      synthetic peptide. These results suggest that the alpha-, beta-, and gamma
      secretase cleavages are conserved in yeast and that P. pastoris may offer an
      alternative to mammalian cells to identify the proteases involved in the
      generation of AD betaA4 amyloid.

PMID- 9778374
TI  - Metal-thiolate clusters in the C-terminal domain of human neuronal growth
      inhibitory factor (GIF).
AB  - Neuronal growth inhibitory factor (GIF), a metallothionein-like protein
      (metallothionein-3), impairs the survival and neurite formation of cultured
      neurons. Native GIF contains 4 Cu(I) and three Zn(II) ions organized in
      homometallic metal-thiolate clusters. However, the cluster localization is not
      known. In this study, the metal-thiolate clusters formed with monovalent and
      divalent metal ions in the C-terminal domain of human GIF [GIF(32-68)] containing
      11 cysteines were investigated. The cluster formation was followed by using
      electronic absorption, circular dichroism (CD), and magnetic circular dichroism
      (MCD) spectroscopy, and in the case of Cu(I) complexes also by luminescence
      spectroscopy at 77 K. Spectroscopic studies on the Cu(I)-GIF(32-68) complexes
      showed the successive formation of two air-sensitive Cu4S8-9- and Cu6S11
      clusters. With Zn(II) and Cd(II) ions, a well-defined M4S11-cluster is formed in
      which each metal ion is tetrahedrally coordinated by cysteine thiolates. In the
      113Cd NMR spectra of 113Cd4-GIF(32-68), recorded at 293 and 323 K, all four 113Cd
      resonances at 672.8, 620.9, 629.6, and 564.2 ppm were observed only at 323 K.
      Their detection at elevated temperature indicates a conformational flexibility of
      this domain. Evidence for the existence of a Cd6-GIF(32-68) complex, contaning
      two more weakly bound Cd(II) ions, was also obtained. The formation of this
      complex requires the transformation of some originally terminal thiolates of the
      Cd4S11-cluster to bridging thiolates, suggesting a more accessible cluster
      structure. Such properties of Cd4-GIF(32-68) have not been observed with the
      Cd4S11-cluster in the isolated alpha-domain (amino acids 31-61) of
      metallothioneins. The significance of Cu- and Zn-clusters for the structure of
      native GIF is discussed.

PMID- 9778376
TI  - Drug binding and nucleotide hydrolyzability are essential requirements in the
      vanadate-induced inhibition of the human P-glycoprotein ATPase.
AB  - P-glycoprotein (Pgp) mediates drug transport utilizing the energy released from
      ATP hydrolysis. However, the mechanism by which Pgp couples these two reactions
      remains unclear. The present work is undertaken to describe kinetically the first
      step, which is the interdependence of nucleotide and drug binding to the Pgp by
      the use of vanadate. Preincubation of human Pgp expressed in Sf9 insect cells
      with vanadate in the presence of Mg2+, ATP, and verapamil resulted in nearly
      complete and stable inhibition of the drug-stimulated ATPase function. In
      contrast, the Pgp ATPase function was nearly unaffected when Mg2+, ATP, or
      verapamil was omitted. Inhibition was highly specific for divalent cations that
      support ATP hydrolysis, for nucleotides that serve as substrates of hydrolysis,
      and for those drugs/compounds that interact with the drug-binding/transport sites
      of the Pgp. Kinetic analysis indicated that vanadate inhibition was MgATP
      concentration-dependent with an apparent Ki value similar to the apparent Km,
      suggesting that MgATP was bound to a similar ATP-binding site in both the ATPase
      inhibition and activation reactions. In support of this conclusion, vanadate, in
      the presence of Mg2+ and verapamil, caused selective trapping of 8-azido [alpha
      32P] ATP and covalent labeling of ATP-binding site in the Pgp. Differences were
      observed in the vanadate-induced inhibition of wild-type and Val185 mutant Pgp's
      with different drug/compounds. These results suggested that the affinity of the
      interacting drug/compound is a constant and influences the overall stability of
      the inhibited Pgp species. Possible implications of these observations for the
      coupling of ATP hydrolysis to drug transport are discussed.

PMID- 9778375
TI  - Remnant high density lipoprotein2 particles produced by hepatic lipase display
      high-affinity binding and increased endocytosis into a human hepatoma cell line
      (HEPG2).
AB  - We had previously shown that hepatic lipase plays a prominent role in promoting
      the generation of pre-beta HDL particles from triglyceride rich HDL2, leaving an
      alpha-HDL particle of decreased size that was named "remnant HDL2" [Barrans, A.,
      et al. (1994) J. Biol. Chem. 269, 11572-11577]. Interestingly, this remnant HDL2
      was rapidly cleared by the liver, suggesting a particularly high affinity of
      those remnant HDL2 for liver cells. In the present study, we attempted to
      characterize the interaction of remnant HDL2 with HepG2 cells, as compared to
      those of native triglyceride rich HDL2. Two main observations were made. First,
      while triglyceride rich HDL2 particles were able to bind only the low-affinity
      binding sites, the remaining particle generated after hepatic lipase lipolysis
      the remnant HDL2 was further able to bind to the high-affinity binding sites.
      Competition experiments indicate that these two remnant HDL2 binding sites were
      the same as the two HDL3 binding sites previously described [Barbaras, R., et al.
      (1994) Biochemistry 33, 2335-2340]. This is the first observation on the
      remodeling dependence of HDL binding onto hepatocytes. Second, following binding
      on those two binding sites, the remnant HDL2 were faster internalized and in
      higher amounts than the native triglyceride rich HDL2. All together, these
      observations suggest that the continuous remodeling of HDL induces different
      binding and internalization characteristics of the HDL particles and that the
      high-affinity HDL binding sites might trigger the internalization of apo HDL
      through the low-affinity binding sites.

PMID- 9778377
TI  - Galactose mutarotase: purification, characterization, and investigations of two
      important histidine residues.
AB  - Galactose mutarotase catalyzes the interconversion of alpha- and beta-anomers of
      aldoses and is a recently identified member of the gal operon of Escherichia coli
      and participant in the Leloir pathway [Bouffard et al. (1994) J. Mol. Biol. 244,
      269-278]. We report the purification and characterization of this enzyme, as well
      as mechanistic studies involving chemical modification with diethylpyrocarbonate
      (DEPC) and site-directed mutagenesis demonstrating the significance of two
      conserved histidine residues. The enzyme lacks metal ions and oxidoreduction
      cofactors, and an extinction coefficient of (6.2 +/- 0.4) x 10(4) M-1 cm-1 has
      been measured by quantitative amino acid analysis. The catalytic mechanism is
      likely concerted general acid/general base. Experiments involving modification
      with DEPC suggest that a histidine is essential and is protected by substrate.
      Furthermore, site-directed mutagenesis of two conserved histidines was performed,
      and characterization of these mutants (His104Gln and His175Asn) illustrates the
      significance of these residues. Kinetic analysis of H104Q demonstrates an
      increase in KM of about 600-fold, a decrease in kcat of approximately 7-fold, and
      a 4000-fold decrease in kcat/KM as compared to the wild-type enzyme. The activity
      of His175Asn mutant, on the other hand, was too low to be measured accurately,
      and His 175 remains a candidate for the general base. These mutants were also
      subjected to DEPC modification, and results are consistent with the presence of
      two important histidines positioned closely together in the active site.

PMID- 9778378
TI  - Identification and purification of diphosphoinositol pentakisphosphate kinase,
      which synthesizes the inositol pyrophosphate bis(diphospho)inositol
      tetrakisphosphate.
AB  - Diphosphoinositol pentakisphosphate (PP-IP5) and bis(diphospho)inositol
      tetrakisphosphate (bis-PP-IP4) were recently identified as inositol phosphates
      which possess pyrophosphate bonds. The molecular mechanisms that regulate the
      cellular levels of these compounds are not yet characterized. To pursue this
      question, we have previously purified an inositol hexakisphosphate (IP6) kinase
      from rat brain supernatants [Voglmaier, S. M., et al. (1996) Proc. Natl. Acad.
      Sci. U.S.A. 93, 4305-4310]. We now report the identification and purification of
      another novel kinase, diphosphoinositol pentakisphosphate (PP-IP5) kinase, which
      uses PP-IP5 as a substrate to form bis(diphospho)inositol tetrakisphosphate (bis
      PP-IP4) in soluble fractions of rat forebrain. The purified protein, a monomer of
      56 kDa, displays high affinity (Km = 0.7 microM) and selectivity for PP-IP5 as a
      substrate. The purified enzyme also can transfer a phosphate from bis-PP-IP4 to
      ADP to form ATP. This ATP synthase activity is an indication of the high
      phosphoryl group transfer potential of bis-PP-IP4 and may represent a
      physiological role for PP-IP5 and bis-PP-IP4.

PMID- 9778380
TI  - ASSISTANCE IN MANUSCRIPT PRESENTATION. INTRODUCING A NEW SERVICE FROM CBI (FOR
      AUTHORS WHOSE FIRST LANGUAGE IS NOT ENGLISH).

PMID- 9778382
TI  - EDITORIAL. 'SPLITTING' AND 'LUMPING' RECONCILED?

PMID- 9778379
TI  - Amino acid residues involved in determining the processivity of the 3'-5'
      exonuclease activity in a family B DNA polymerase from the thermoacidophilic
      archaeon Sulfolobus solfataricus.
AB  - Herein, we report on the mutational analysis of a 70-amino acid segment (region
      1, residues 438-508) of family B DNA polymerase from the thermoacidophilic
      archaeon Sulfolobus solfataricus (Sso DNA pol). Region 1, which lies between the
      Exo III sequence and the similarity motif D- -SLYP, connects the exonuclease and
      polymerase domains of Sso DNA pol. Two C-terminally deleted forms of the enzyme,
      proteins N438 (residues 1-438) and N508 (residues 1-508), were overproduced in
      the recombinant form and biochemically characterized. They contain the three
      evolutionarily conserved Exo motifs, but differ in the extent of the C-terminal
      deletion, since only N508 includes region 1. Both have been found to retain a
      Mn2+-dependent 3'-5' exonuclease activity, whose thermal stability appears to be
      increased in comparison to that of the full-sized enzyme. Assays for processive
      3'-5' exonuclease activity, carried out with the heparin trap method on a 24-base
      oligonucleotide, have revealed that protein N508, as well as the full-length Sso
      DNA pol, retains a level of processivity of the degradative function
      substantially higher than that for protein N438. In addition, six site-specific
      mutations have been introduced at the highly conserved Y-GG/A motif, which has
      been found within Sso DNA pol region 1. All mutant proteins (Lys491Ile,
      Tyr495Ser, Lys496Ile, Gly497Ala, and Ala498Val) display increased processivity of
      their 3'-5' exonuclease activity, with the exception of protein Tyr495Phe. By a
      steady-state kinetic analysis of the exonucleolytic reaction on a 24-base
      oligonucleotide, the above site-specific mutations have been found to affect Km
      values consistently with the observed differences in the processivity values,
      whereas the effect on the kcat values seems to be less important. The results
      from this mutational analysis indicate that region 1 is involved in determining
      the processivity of the proofreading function, directly interacting with the
      nucleic acid substrate.

PMID- 9778383
TI  - Cuticular metals: quantification and mapping by complementary techniques.
AB  - Metal-replete cuticle was characterised by back-scattered electron imaging,
      secondary ion mass spectrometry, proton induced X-ray emission and SEM-X-ray
      microanalysis. Each technique was found to have singular advantages and
      limitations for localising and quantifying metal content. Manganese and zinc were
      found coincident at the mandibular cutting edge of the leaf-cutting ant Atta
      sexdens; these two metals were found in different zones within jaws of the
      ragworm, Nereis virens; while only manganese was found in the jaws of the termite
      C. cumulans. Copyright 1997 Academic Press

PMID- 9778384
TI  - Relationship between Oil-Water Interfacial Tension and Oily Soil Removal in Mixed
      Surfactant Systems.
AB  - Detergency of oily soil is a complex kinetic process that includes contributions
      from the wash system physical properties, time and temperature of wash, and the
      hydrodynamic forces exerted during the wash process. Generally, surfactant
      mixtures that exhibit a low oil-water interfacial tension are considered to
      provide superior oily soil detergency. In our investigations, we measured the oil
      water interfacial tension for C12EO3/NaLAS and C12EO7/NaLAS blends as a function
      of temperature (18-80 degreesC) and time (0-60 min). The oil-water interfacial
      tension was found to decrease as a function of time for all blends containing
      nonionic surfactants, and this decline was most rapid for blends containing a
      higher fraction of ethoxylated alcohol with less than 3 mol of ethylene oxide. It
      is proposed that the diffusion of this hydrophobic fraction into the oil phase
      leads to the measured decline in the oil-water interfacial tension. Also, due to
      this limitation, no general correlation of oil-water interfacial tension with
      oily soil removal was observed. In view of these observations, it appears that
      the measurement of the oil-water interfacial tension (using a spinning drop
      tensiometer) for solutions containing hydrophobic surfactants may give misleading
      results. Copyright 1998 Academic Press.

PMID- 9778385
TI  - A Thermodynamic Model for Contact Angle Hysteresis.
AB  - Thermodynamic expressions for the free energy of contact angle hysteresis have
      been derived assuming that wetting can be modeled as an adsorption-desorption
      process. The cause of hysteresis is not specified; it could be due to surface
      imperfections or simply irreversible interaction of the contact liquid and solid.
      The model shows that even near-zero contact angles can represent substantial free
      energies. Experimental data from previous work were used to calculate free
      energies for a variety of polymer and surfactant surfaces. For each surface, a
      variety of organic liquids and water gave similar free energy values. Nonpolar
      polymer surfaces gave free energies that corresponded to van der Waals
      interactions. Free energies were usually higher for polar polymers, arising from
      stronger interactions that may involve more extensive restructuring of groups at
      the interface. Copyright 1998 Academic Press.

PMID- 9778386
TI  - The Influence of Surfactants on the Hydrodynamics of Surface Wetting.
AB  - The hydrodynamic model of steady wetting developed by Boender et al. is extended
      to include the effect of a (nonionic) surfactant in the limiting case of
      negligible diffusion and low concentrations, confining attention to steady
      wetting between parallel plates. The approximation that the meniscus inclination
      becomes equal to the static contact angle at a distance from the solid of the
      order of a molecular dimension is extended to take account of the local
      surfactant concentration, making use of Young's law. A second inner boundary
      condition, provided by a surfactant balance at the contact line, places a
      restriction on the speed at which the interface is shed, leading to surfactant
      accumulation and partial or almost total immobilization of the interface which
      reduces the wetting speed. Under certain conditions, this immobilization is self
      stabilizing, leading to hysteresis effects. Both these effects and the reduced
      wetting speed correspond with results reported in the literature. Copyright 1998
      Academic Press.

PMID- 9778387
TI  - Approximate Solution for the Spreading of a Droplet on a Smooth Solid Surface.
AB  - The same approach used by Boender, Chesters, and van der Zanden in the context of
      an advancing liquid-gas meniscus in a capillary tube is extended to the case of
      spontaneous spreading of a droplet on an ideal solid surface. The result is an
      ordinary differential equation for the droplet profile which can be solved if the
      meniscus inclination phi0 is specified at some distance lambda from the solid. As
      in the capillary-tube case, good agreement is obtained with experimental data
      obtained by the authors and by others if phi0 is set equal to the static contact
      angle (zero in cases investigated experimentally), taking lambda of the order of
      a molecular dimension (1 nm). A comparison of predicted dynamic contact angles in
      the spreading-drop and capillary-tube cases for given values of the capillary
      number indicates only a weak dependence of the behavior on the system geometry.
      De Gennes and co-workers have predicted that during the final stages of spreading
      the inner length scale lambda should be determined by the effects of disjoining
      pressure in the thin film adjacent to the contact line rather than by molecular
      dimensions. The lambda value implied by their model is derived, thereby
      establishing the regime of spreading in which such effects should be dominant.
      The observed behavior in this regime is found to correspond somewhat better with
      a lambda value of the order of a molecular dimension, although the differences
      are small. Although the explanation probably lies in the nonideality of even the
      smoothest surfaces, this result suggests that the simplest model, based on a
      single lambda value of the order of 1 nm, should provide an excellent predictive
      tool. Copyright 1998 Academic Press.

PMID- 9778388
TI  - Differences in Thinning Processes of Some Vesicular Foam Films with Different
      Compositions.
AB  - Thinning processes of foam films are observed for various phospholipid vesicle
      suspensions by the horizontal suspending method using an interferometric
      microscopy system. It is found that the phospholipid components that construct
      the bilayer of unilamellar vesicles or micelles affect the thinning process
      behavior of the plane-parallel liquid film. In the case of vesicle from egg
      phosphatidylcholine (PC), the plane-parallel foam film made of its suspension
      shows a gradual but inhomogeneous slow thinning process, which differs from the
      stepwise thinning process of thin liquid films with silica or micelle suspensions
      reported in previous investigations. However, when lysophosphatidylcholine was
      mixed with egg PC, channel formation and coexistence of black thin films and
      thicker regions were observed. Copyright 1998 Academic Press.

PMID- 9778389
TI  - Impact of Bulk Phase Transitions and Wetting Transitions on Adsorption Isotherms
      in Binary Systems in Contact with Solid.
AB  - This paper presents several studies essentially on the solid/liquid interface.
      The studied system is the liquid binary mixture water-2,5dimethylpyridine
      (2,5DMP) in contact with an amorphous silica (Aerosil type). The study of wetting
      along the two-liquid bulk phases coexistence in contact with silica allows the
      determination of a wetting transition temperature, which is an important
      parameter for the adsorption behavior at coexistence. The adsorption isotherms in
      a diluted phase and in a concentrated phase present some very significant
      features. In diluted solutions the isotherms show a succession of plateaus; these
      transitions of layers persist in concentrated phases presenting a sequence of
      maxima and minima of relative adsorption (Gibbs adsorption) of 2,5DMP with
      respect to water. In concentrated solutions, they interfere with the prewetting
      that gives an original shape to the isotherms in concentrated solutions. These
      adsorption measurements were completed by activity measurements which allow one
      to obtain the chemical potential of mixtures and linked information. The whole
      study shows the behavior of colloidal suspensions close to bulk phase changes.
      Copyright 1998 Academic Press.

PMID- 9778390
TI  - Electroviscoelastic Instability of a Kelvin Fluid Layer Influenced by a Periodic
      Electric Force.
AB  - The electroviscoelastic stability of a Kelvin fluid layer is discussed in the
      presence of the field periodicity. The surface elevations are governed by two
      transcendental coupled equations of Mathieu type which have not been attempted
      before. Analysis for the surface waves in axisymmetric modes and antisymmetric
      deformation which are governed by a single transcendental Mathieu equation is
      considered. The method of multiple scales expansion is applied to the stability
      analysis. The solution and the characteristic curves are obtained analytically.
      It is shown that the region between the two branches of the characteristic curves
      is unstable, whereas all points which lie outside the characteristic curves are
      stable. The special case of large viscosity is introduced for numerical
      calculations. It is found that the increase of kinematic viscosity, field
      frequency, and the elasticity parameter possesses a dual role in a damping
      nature. The phenomena of the coupled resonance is observed. The resonance region
      and the resonance points are functions of viscosity, elasticity, and field
      frequency, with nonlinear relations in the wavenumber. Copyright 1998 Academic
      Press.

PMID- 9778392
TI  - Properties of Anionic-Cationic Adsorption Films in the Presence of Inorganic
      Electrolytes, 2.
AB  - The composition and mutual interaction of the components in anionic-cationic
      adsorption films have been determined by using a regular solution model for the
      mixed monolayers. Equimolar mixtures of surfactants that differ markedly in their
      surface activity (decylpyridinium chloride and sodium butylsulfonate) have been
      investigated. A marked asymmetry of the composition of mixed adsorption films, as
      well as mutual attraction of the adsorbed components (negative values of surface
      interaction parameter beta) have been found in these systems. The effect of the
      ionic strength and kind of the inorganic electrolyte on the surface interactions
      is similar, as in the case of mixtures of decylpyridinium chloride and sodium
      alkylsulfonates with hydrocarbon chains longer than the butyl ones that were
      previously investigated. Copyright 1998 Academic Press.

PMID- 9778391
TI  - Equilibrium Penetration of DMPC Monolayers by Sodium Cholate.
AB  - The interaction of dimyristoyl phosphatidylcholine (DMPC) with sodium cholate was
      studied by equilibrium penetration measurements. Surface pressure-area isotherms
      for DMPC on substrates containing various concentrations of sodium cholate are
      presented. From these isotherms, the saturation adsorptions of the bile salt for
      various surface concentrations of DMPC were calculated. It is shown that the
      equilibrium penetration of DMPC monolayers by sodium cholate can be
      satisfactorily described by the accessible-area theory of McGregor and Barnes. A
      plot of the surface excess concentration of cholate against the inverse of the
      area per DMPC molecule is linear. This plot yields a value for the adsorption
      into the accessible areas of the monolayer-covered surface that corresponds to
      the adsorption of cholate in a monolayer-free surface. The cholate molecules lie
      flat on the air-water interface. The effective cross-sectional area of the DMPC
      in the mixed monolayer is similar to the area occupied by a DMPC molecule in a
      close-packed liquid expanded monolayer. The composition of the penetrated
      monolayer at different areas per DMPC molecule was calculated. The penetration of
      cholate into DMPC monolayers is correlated with different results taken from the
      literature dealing with the incorporation of bile salts into lecithin bilayers.
      Copyright 1998 Academic Press.

PMID- 9778393
TI  - Rheology and Flocculation of Oil-in-Water Emulsions Made with Mixtures of alphas1
      Casein + beta-Casein.
AB  - The influence of the composition of a mixed binary protein emulsifier composed of
      alphas1-casein + beta-casein on the rheology of concentrated oil-in-water
      emulsions (45 vol% oil, 5 wt% protein, pH 7) has been investigated over the
      temperature range 0-40 degreesC. Controlled stress viscometric data are reported
      over the shear stress range 0.1-30 Pa for systems with alphas1-casein/beta-casein
      ratios of 100:0, 98:2, 95:5, 90:10, 75:25, 50:50, and 0:100. The pure casein
      emulsions showed substantially different temperature-dependent rheology, and
      there was observed to be a pronounced maximum in the small-deformation complex
      modulus of the pure alphas1-casein emulsion in the range 30-40 degreesC. In the
      emulsions containing >/=90% alphas1-casein in the emulsifier mixture, all of the
      beta-casein present was found to be associated with the surface of the droplets.
      Average droplet sizes and protein surface coverages were higher in the mixed
      casein systems than in the equivalent pure casein systems. The strongly
      pseudoplastic character of the emulsions is consistent with extensive reversible
      flocculation caused probably by a depletion mechanism involving unadsorbed
      protein. The degree of flocculation is sensitive to temperature and to the
      alphas1-casein/beta-casein ratio. The results can be interpreted in terms of
      changes in protein self-assembly and adsorbed layer structure which influence the
      strength of the interdroplet interactions and hence the rheological behavior of
      the emulsions. There is some evidence of a specific role for alphas1-casein-beta
      casein complexes in these systems. Copyright 1998 Academic Press.

PMID- 9778394
TI  - Surface Titrations of Perlite Suspensions.
AB  - The surface charge behaviour of unexpanded and expanded perlite samples in KNO3
      and NaCl solutions were investigated as a function of pH and ionic strength. The
      solutions of KNO3 and NaCl ranging from 10(-3) to 1.0 M were used. The
      potentiometric titration method was used to determine the surface charge of
      perlite samples. It was confirmed that the perlite samples had no the point of
      zero charge and was negatively charged in the pH range of 3-10. The double
      extrapolation method was used for determining the intrinsic equilibrium constants
      for simple ionization and complex ionization reactions. The values obtained are
      pKinta2 = 2.5 and p*KintK+ = 2.3 in KNO3 solutions and pKinta2 = 3.0 and
      p*KintNa+ = 2.4 in NaCl solutions for unexpanded perlite, and pKinta2 = 2.6 and
      p*KintK+ = 2.4 in KNO3 solutions and pKinta2 = 2.7 and pKintNa+ = 2.4 in NaCl
      solutions for expanded perlite. Copyright 1998 Academic Press.

PMID- 9778395
TI  - Surface Elasticity and Viscosity from Oscillating Bubbles Measured by Automatic
      Axisymmetric Drop Shape Analysis.
AB  - The pendant drop/sessile drop instrument developed by our group and based on
      video image analysis has been enhanced to measure oscillating drops and bubbles
      at a rate up to 25 pictures per second. Data analysis has been developed to
      analyze the results from sinusoidal oscillations in terms of dilatational surface
      elasticity and viscosity. The polymers ethylhydroxyethyl cellulose (EHEC) and two
      different poly(oxyethylene)-poly(oxypropylene) ABA block copolymers (PE6200 and
      PE6800) have been investigated at the air-water interface regarding rate of
      adsorption and surface dilatational properties. The polymers give surface
      pressures in the region 20-30 mN m-1, the surface elastic moduli are between 4
      and 30 mN m-1, and the viscous moduli are generally low, from 0 to 6 mN m-1. The
      elastic moduli increase with increasing frequency, but both the slope and the
      concentration dependency vary. For the most water-insoluble polymer, EHEC, the
      modulus increases with polymer concentration, the relatively hydrophobic polymer
      PE6200 shows the opposite behavior, and the most water-soluble polymer, PE6800,
      shows a maximum in the equilibrium elasticity. These observations can be
      explained by the changes in the molecular orientation in the surface layer as
      reflected in pi vs A isotherms. The PE6200 polymer also shows a higher viscous
      modulus, which may be explained by diffusional transport between surface and
      bulk. Copyright 1998 Academic Press.

PMID- 9778396
TI  - FTIR and UV-Vis Spectroscopic Studies of Black Soap Film.
AB  - FTIR and UV-vis spectroscopies have been employed to investigate the self
      assembly features of a black soap film (BSF) prepared from aqueous solution
      consisting of 10(-2) M cetyltrimethylammonium bromide (CTAB) and 10(-3) M
      thiazole yellow (TY) in the liquid-crystalline and gel states, respectively. The
      construction of two surfactant monolayers of the soap film is independent of the
      thickness of aqueous core, and the thickness is approximately 1.7 nm at
      equilibrium. In the liquid-crystalline state, the methylene segments of the
      hydrocarbon chains are averagely oriented at an angle of 70 degrees with respect
      to the film normal, and the alkyl chains take a long-range interaction to improve
      the film elasticity. The TY molecules in the film are horizontally aligned at the
      monolayer interface in the J-aggregate form. The double-negatively charged TY
      aggregate greatly enhances the film stability. Dye neutral red is further
      introduced into the CTAB soap film, the film lifetime is related to the type of
      the added dyes, in the order of cationic < nonionic < anionic. Copyright 1998
      Academic Press.

PMID- 9778397
TI  - Preparation of Monodisperse, Micron-Sized Polystyrene Particles with Single-Stage
      Polymerization in Aqueous Media.
AB  - A single-stage polymerization technique, proposed for producing micron-sized
      polymer particles in aqueous media by Gu and Konno, was examined. Styrene was
      used for the monomer, potassium persulfate for the initiator, and
      cetyltrimethylammonium bromide and sodium dodecyl sulfate were used for the ionic
      surfactants to control the aggregation of the particles during the reaction.
      Particle-size distributions and monomer-to-polymer conversions were measured over
      a range of initiator concentration (2-8 mmol/dm3 H2O), stirring speed (200-400
      rpm), surfactant addition time and monomer concentration (1.1-2.2 mol/dm3 H2O).
      Changes in the initiator concentration and stirring speed did not bring about
      significant effect on the particle-size distributions. On the other hand, the
      addition of time affected the coefficient of variation of the particle-size
      distribution, but it had no significant effect on the average diameter of the
      particles. An increase in the monomer concentration enlarged the average size
      without lowering the coefficient of variation of particle-size distribution.
      Monodisperse polystyrene particles with an average diameter of 3.3 um and a
      coefficient of variation of particle size distribution 7% could be prepared with
      the present technique. Copyright 1998 Academic Press.

PMID- 9778398
TI  - Observation of Oriented Close-Packed Lattice Planes in Polycrystalline Hard
      Sphere Solids.
AB  - We report time-resolved Bragg scattering experiments on solidifying colloidal
      suspensions of hard spheres. The polar angle-averaged, integrated intensity of
      the (111) and (311) reflections show a transient, two-step behavior below
      melting, which depends in a complex way on the volume fraction and is not present
      for (200) or (220). Detailed analysis of the full two-dimensional scattering
      pattern reveals intensity maxima of sixfold symmetry close to the position of the
      (111) and (311) Debye-Scherrer rings. These can be explained assuming oriented
      crystals with close-packed planes parallel to the container walls. We show that
      the observed temporal behavior is due to competing homogeneous and heterogeneous
      nucleation and growth scenarios. Copyright 1998 Academic Press.

PMID- 9778399
TI  - The Limited Swelling of Montmorillonite.
AB  - The attraction forces responsible for the occurrence of limited swelling of
      montmorillonite having divalent counterions were evaluated from (a) the
      electrostatic attraction between the negative charges of one surface and the
      effective charges of the counterions of the other interlayer surface and (b) van
      der Waals attraction between the two interlayer surfaces. Both methods of
      calculation almost account for the force required to maintain limited swelling of
      the clay. It is found that a Hamaker constant of 2.25 x 10(-13) erg in place of
      2.72 x 10(-13) erg and a counterion charge screening factor of 0.82[1 - exp(
      kappax)] in place of [1 - exp(-kappax)] reproduce the true value of the
      attraction force. Copyright 1998 Academic Press.

PMID- 9778400
TI  - Electro-optic Properties of Colloidal Crystals As Studied by Reflection
      Spectroscopy.
AB  - Electro-optic properties of colloidal crystals of silica spheres in the
      exhaustively deionized aqueous suspension have been studied by the reflection
      spectroscopy using a T-type cell. Acoustic shear waves are induced when sine-wave
      electric fields ranging from 0.01 to 1 Hz are applied. Modulation effects of the
      crystals on the applied AC fields such as phase delay, change in response
      intensity, waveform transformation, and harmonics generation are observed. The
      shear waves propagate outside the electrodes where the electric field is absent.
      The synchronous fluctuation of the colloidal spheres including expanded
      electrical double layers in the crystal lattice will be one of the main causes of
      the electro-optic nature of the crystals. Copyright 1998 Academic Press.

PMID- 9778401
TI  - Mechanism of the Shape and Structure Control of Monodispersed alpha-Fe2O3
      Particles by Sulfate Ions.
AB  - The characteristics of the adsorption of sulfate ions to hematite (alpha-Fe2O3)
      particles have been studied to elucidate the anisotropic growth of hematite
      particles in the presence of sulfate ions. Sulfate ions were actually found to be
      most strongly adsorbed to crystal faces parallel to the c-axis of the hexagonal
      crystal system from the adsorption isotherms of sulfate to hematite particles of
      different crystal habits, in accord with the retardation of their growth in the
      direction normal to the c-axis. It was found from FTIR spectroscopy that the
      adsorbed sulfate ions on the faces parallel to the c-axis, such as the {110} and
      {100} faces, or on {012} faces took the bidentate structure to Fe ions on the
      surfaces, while a monodentate structure was suggested for sulfate ions on the c
      planes ({001} faces). The adsorbed amount of sulfate ions to the {012} faces of
      hematite at 100 degreesC decreased with increasing pH and became almost zero at
      pH >/=5, suggesting that the shape control with sulfate is possible only in the
      acidic media at pH < 5. EDX and chemical analysis revealed that sulfate ions were
      almost uniformly incorporated into the ellipsoidal or peanut-type particles
      during their growth in the presence of sulfate ions. On the other hand, sulfate
      ions in the solution phase with a high concentration of chloride ions such as 3.0
      mol dm-3 were likely to be present in the form of free ions without forming a
      complex with Fe3+, as suggested from UV spectroscopy at 25 degreesC. When the
      concentration of sulfate ions in the solution phase exceeded the level for shape
      control of hematite, precipitation of acicular alpha-FeOOH (goethite) was
      observed. If hematite particles were present in such a system, alpha-FeOOH was
      grown as whiskers on the hematite particles. When [SO2-4] in the solution phase
      was higher than 0.1 mol dm-3, precipitation of basic ferric sulfate was also
      observed in addition to the growth of alpha-FeOOH whiskers on hematite. Copyright
      1998 Academic Press.

PMID- 9778402
TI  - Characterization of Turbid Colloidal Suspensions Using Light Scattering
      Techniques Combined with Cross-Correlation Methods.
AB  - The ability to characterize colloidal suspensions by means of dynamic light
      scattering is in general limited to systems with negligible contributions from
      multiple scattering. For larger particle sizes with high scattering contrast this
      immediately limits the technique to very low concentrations. A promising solution
      of this problem is to suppress multiple scattering in dynamic light scattering
      experiments using cross-correlation schemes. Based on these considerations we
      have constructed a so-called 3D cross-correlation experiment with which we are
      able to characterize extremely turbid suspensions. We have measured monomodal and
      bimodal suspensions of latex particles of relatively high volume fraction. The
      results show clearly that we are able to measure the dynamic structure factor in
      concentrated polydisperse suspensions with dynamic light scattering. Combining
      static and dynamic light scattering measurements for characterizing turbid
      suspensions the single scattering particle form factor and also the static
      structure factor can be evaluated. We demonstrate that the implementation of a 3D
      cross-correlation scheme is a powerful method in suppressing multiple scattering
      contributions in light scattering experiments and opens a wide field of
      characterization of colloidal dispersions with high turbidity without having to
      resort to high dilution. Copyright 1998 Academic Press.

PMID- 9778403
TI  - Pore Size Analysis of MCM-41 Type Adsorbents by Means of Nitrogen and Argon
      Adsorption.
AB  - Methods of nonlocal density functional theory (NLDFT), proposed recently for
      predictions of adsorption equilibrium and calculations of pore size distributions
      in micro- and mesoporous materials, were tested on reference MCM-41 materials.
      Five newly synthesized MCM-41 adsorbents with presumably uniform pore channels
      varying from 32 to 45 A were characterized by X-ray diffraction (XRD), nitrogen
      adsorption at 77 K, and argon adsorption at 77 and 87 K. New sets of
      intermolecular interaction parameters of the NLDFT model for N2 and Ar adsorption
      on MCM-41 were determined. The parameters were specified to reproduce the bulk
      liquid-gas equilibrium densities and pressures, liquid-gas interfacial tensions,
      and standard adsorption isotherms on nonporous surfaces in the multilayer
      adsorption region. The pore size distributions calculated from the desorption
      branches of the experimental isotherms measured at three different temperatures
      were consistent with each other. Comparison of the NLDFT-calculated pore sizes
      with XRD data showed that the thickness of pore walls in the MCM-41 samples under
      consideration varied from ca. 6 to 12 A. We found no correlation between the pore
      size and the pore wall thickness. The results obtained support the NLDFT model as
      a suitable tool for characterizing nanoporous materials and predicting adsorption
      equilibrium. The MCM-41 samples studied can be used as references for adsorption
      measurements. Copyright 1998 Academic Press.

PMID- 9778404
TI  - Effect of Tannic Acid on the zeta Potential, Sorption, and Surface Free Energy in
      the Process of Dyeing of Leacril with a Cationic Dye.
AB  - The behavior of the surface free energy in the process of dyeing Leacril
      pretreated with tannic acid and subsequently dyeing with the cationic dye
      Rhodamine B has been studied. Also the electrokinetic behavior of these systems
      has been analyzed by studying the zeta potential, which has been obtained by
      means of the streaming potential technique. Values more significative of the zeta
      potential of these systems have been obtained using the three models of
      capillaries existing in the literature. The qualitative behavior of the zeta
      potential is the same for the three models of capillaries tested in this paper.
      These models are those of Goring and Mason, Biefer and Mason, and Chang and
      Robertson. The zeta potential of the systems analyzed is negative in the range of
      concentration of the dye in the liquid phase from 10(-6) to ca. 10(-4) M of dye.
      In the range of low concentrations (from 10(-6) to ca. 10(-5) M of dye) the zeta
      potential of the system untreated Leacril/Rhodamine B increases in absolute value
      due to increasing hydrophobic attractions between both the hydrophobic chains of
      the dye and the Leacril fibers in aqueous media. In the system Leacril treated
      with tannic acid/Rhodamine B, this increase is also due to the presence of
      hydrogen bonding between the phenolic hydroxyl groups of the tannic acid and the
      sulfonate and sulfate end groups of Leacril fibers. For concentrations of dye
      between 10(-5) and 10(-4) M of dye in solution, the zeta potential decreases in
      absolute value due to the electrostatic attractions between the groups negatively
      charged in the fiber and the cation of the dye. The zeta potential changes its
      sign at the highest concentrations of dye used in this work. The adsorption of
      Rhodamine B onto both untreated Leacril and Leacril treated with tannic acid is
      favored by the increasing temperature of adsorption. The behavior of the
      components of the surface free energy obtained by the thin-layer wicking
      technique led us to consider that the cationic dye Rhodamine B is adsorbed on the
      surface of both untreated Leacril and Leacril treated with tannic acid by Lewis
      acid-base interactions. Copyright 1998 Academic Press.

PMID- 9778405
TI  - Characterization of Grafted Poly(ethylene glycol) on Si Wafers Using Scanning
      Probe Microscopy.
AB  - The uniformity and surface topography of grafted poly(ethylene glycol) (PEG)
      coatings were characterized at the microscale as a function of grafting
      temperature (grafting density) using scanning probe microscopy. Images of PEG
      coated silicon wafers show isolated domains which decrease in size and increase
      in surface density with increasing grafting temperature. Domain sizes appeared to
      correlate with the polarity of the solvent used for imaging. Roughness
      measurements of the PEG layers were obtained. The results are relevant in
      relation to the biomedically significant ability of PEG coatings to mask surface
      features such as charge detected via zeta potential measurements. Copyright 1998
      Academic Press.

PMID- 9778406
TI  - Age-related melanogenesis in the eye of mice, studied by microautoradiography of
      3H-methimazole, a specific marker of melanin synthesis.
AB  - Whether melanogenesis occurs in adult eyes is still a matter of controversy. It
      has been widely held that the pigment epithelial cells are fully melanized at
      birth, and that the uveal melanocytes cease their melanin production in the very
      young individual. Therefore there should be no turnover of melanin in the adult
      eye. A number of studies have, however, demonstrated that the enzyme involved in
      melanin synthesis, tyrosinase, seems to be active also in the adult eye. The
      recent observation that a prostaglandin analogue, used in glaucoma therapy,
      caused increased iridal pigmentation in the treated eye, but not in the untreated
      eye, of adult monkeys and in humans, indicate that the adult eye at least has the
      capacity to produce melanin. In the present study 3H-methimazole, a false melanin
      precursor, was administered to a series of DBA-mice, 3 weeks to one year of age.
      The eyes were removed 24 hr after a single i.p. injection of 3H-methimazole.
      Using microautoradiography the incorporation of radioactivity was studied in X
      ray film covered sections comprising the entire eye. A very selective
      accumulation of radioactivity was seen in uveal melanocytes and in the pigment
      epithelial cells in the iris and the ciliary body. The level in the retinal
      pigment epithelium was low in the eyes of all ages. No uptake was seen in any non
      pigmented ocular tissue. The most pronounced accumulation was seen in the pigment
      epithelium and melanocytes in the iris of the young mice, but some activity was
      seen in these cells also in the older mice. The presence of immature melanosomes
      seen in electron micrographs from iridal pigment cells and melanocytes of one
      year old mice indicate that new melanosomes are formed in these cells also in
      adult animals. The results of this study thus strongly indicate that there seems
      to be an active melanin synthesis in the adult eye of the mouse, most pronounced
      in iridal melanocytes and in the iridal pigment epithelium.

PMID- 9778407
TI  - Extracellular matrix changes in human corneas after radial keratotomy.
AB  - Extracellular matrix and basement membrane alterations were identified in human
      corneas after radial keratotomy. Ten normal and five radial keratotomy autopsy
      corneas (two at 6 months post surgery, and three at 3 years post surgery) were
      studied by immunofluorescence with antibodies to 28 extracellular matrix and
      basement membrane components. Outside of radial keratotomy scars, all studied
      components had a normal distribution. Of stromal extracellular matrix, only type
      III collagen accumulated around the scars. The basement membrane around
      epithelial plugs had a normal composition except for type IV collagen. Its alpha1
      alpha2 chains, normally present only in the limbal basement membrane, appeared
      around all plugs. alpha3 and alpha4 chains were very weak or absent in these
      areas, contrary to nonscarred areas. This basement membrane pattern was similar
      to the normal limbal but not to the central corneal pattern. Keratin 3 also had a
      limbal-like, suprabasal expression in the plug epithelium. The stroma around the
      scars accumulated tenascin-C, fibrillin-1, types VIII and XIV collagen, all of
      which were absent from normal corneal basement membrane and extracellular matrix.
      Only tenascin-C showed less staining in anterior scars 3 years post surgery than
      6 months post surgery, but still persisted in posterior scars. Incomplete scar
      healing was evident even 3 years post radial keratotomy. It was manifested by the
      accumulation of abnormal extracellular matrix in the anterior and posterior scars
      and by the limbal-like pattern of type IV collagen isoforms in the basement
      membrane around epithelial plugs.

PMID- 9778408
TI  - Properties of purified lens transglutaminase and regulation of its
      transamidase/crosslinking activity by GTP.
AB  - On account of its protein crosslinking activity, the Ca2+-dependent
      transglutaminase of the lens is likely to be involved in the formation of
      cataracts. We have now purified the rabbit lens enzyme to near homogeneity as
      judged by SDS-PAGE (Mr approximately 78 kDa), and a key feature of the procedure
      was the use of a highly selective affinity chromatographic step with a
      fibronectin fragment as ligand. The catalytic activity of the lens
      transglutaminase, measured by the incorporation of dansylcadaverine into
      dimethylcasein, was compared with those of two similar enzymes isolated from
      human red cells and from guinea pig liver, respectively. All three enzymes were
      inhibited by GTP, but the lens enzyme was most sensitive to inhibition by the
      nucleotide. Moreover, GTP was also shown to inhibit the formation of the
      approximately 55 kDa betacrystallin dimers in the Ca2+-treated rabbit lens
      homogenate, proving that the nucleotide is a negative regulator for the
      crosslinking activity of transglutaminase in this tissue.

PMID- 9778409
TI  - Immunolocalization of CD44 in the dystrophic rat retina.
AB  - The distribution of the cell surface adhesion/receptor molecule CD44 was studied
      in retinas of the Royal College of Surgeons (RCS) rat which exhibits an inherited
      retinal dystrophy. In this animal model, the retinal pigment epithelium fails to
      phagocytize shed photoreceptor outer segment material, a membranous debris layer
      accumulates in the subretinal space and the photoreceptor cells degenerate. Using
      immunoperoxidase and immunogold labeling, CD44 was localized to Muller cell
      apical microvilli in normal rat retinas, as noted in other species. For the RCS
      rat, immunoperoxidase labeling of 18 day and 1 month retinas showed the typical
      microvillar labeling pattern. At 2 months postnatal, following degeneration of
      most of the photoreceptors, a more condensed band of microvillar label was
      observed. At 3 months, when photoreceptor degeneration was virtually complete,
      only distinct regions of dense label remained between the neural retina and
      debris zone. Upon ultrastructural and immunogold analysis, these regions were
      found to contain closely packed Muller cell microvilli. At all ages studied,
      labeling for CD44 in the inner retina did not increase, as it does in other forms
      of retinal degeneration which lack a debris zone. However, by 3 months the debris
      zone was labeled for CD44 indicating that CD44 molecules remain on Muller cell
      microvilli and processes which have extended into and become part of the debris
      zone. This may be caused by an altered distribution of still undetermined ligands
      for CD44 which are present within the interphotoreceptor matrix of the RCS rat
      retina.

PMID- 9778410
TI  - Characterization of melanins in human irides and cultured uveal melanocytes from
      eyes of different colors.
AB  - The presence of eumelanin and pheomelanin in irides from eyes of various colors
      was determined and quantified by a highly specific microanalytical procedure
      based on chemical degradation. Significant differences in the type of melanin
      were observed in the stroma and iris pigment epithelium (IPE) fractions obtained
      by micro-dissection of the iris specimens. Melanin from the IPE is essentially
      eumelanin, while the pigment in IPE-scraped iris (consisting mainly of stroma
      plus anterior IPE) proved to be both eumelanic and pheomelanic. A pheomelanic
      type pigmentation was associated with green irides, while green-blue mixed-color
      irides were mostly eumelanic; by contrast, green-brown mixed-color and brown
      irides could not be placed into either of the two categories and probably feature
      a mixed pigment content. Blue irides invariably exhibited very low pigment
      content. Analysis of cultured iridial melanocytes in the growing stage showed a
      significant shift to pheomelanic pigmentation when compared with those in IPE
      scraped tissues, providing evidence that growth of iridial melanocyte induce a
      marked change of melanin metabolism. After senescence, cultured melanocytes
      exhibited a marked increase in pigment content, most of the variation was
      associated with the eumelanin content. These results represent the first direct
      evidence for the presence of eumelanin and pheomelanin in human irides, and
      suggest that differences in stromal pigmentation are due not only to the
      quantity, but also the nature of the melanin pigment.

PMID- 9778411
TI  - Deamidation and disulfide bonding in human lens gamma-crystallins.
AB  - Detailed analysis of the three gamma-crystallins present in the water-soluble
      portion of human lenses, gammaS, gammaD and gammaC, has identified disulfide
      bonding and deamidation as the major post-translational modifications of these
      crystallins. Chromatographic and mass spectrometric techniques were used to
      isolate and identify water-soluble gamma-crystallins from normal lenses, ages 32
      week gestation, 0 day old, 4 day old, 19, 31, 45 and 55 year old. The amino acid
      sequences of the gamma-crystallins were confirmed and/or corrected by mass
      spectrometric analysis of peptides produced by enzymatic digestion or chemical
      fragmentation of the isolated crystallins. The molecular weight of peptides were
      also used to identify, locate and quantify modifications. Each of the gamma
      crystallins had two disulfide bonds as well as several deamidated glutamine and
      asparagine residues. The extent of disulfide bond formation and deamidation
      appeared to increase with the age of the lens. This examination of normal human
      lens gamma-crystallins, the first detailed characterization of the gamma
      crystallins, will provide a basis for comparison with modifications found in the
      water-insoluble portion and in cataractous lenses.

PMID- 9778412
TI  - Photodynamic effect of a new photosensitizer ATX-S10 on corneal
      neovascularization.
AB  - In order to elucidate the mechanism by which a new photosensitizer ATX-S10 causes
      the photodynamic effect on neovasculature, we investigated the kinetics and
      localization of dye accumulation in the neovascular cornea of rats after systemic
      administration and the development of vascular injury induced by subsequent laser
      irradiation, compared to those in the normal iris. Under a fluorescence
      microscope, the neovascular cornea always exhibited more intense fluorescence
      than the iris between 0.5 and 4 hr after ATX-S10 administration, indicating the
      preferential deposit of dye in the former tissue. The fluorescence was found
      inside the vascular lumen at the earliest time period and thereafter in the
      vascular lining cells, interstitial tissue and infiltrating neutrophils until 6
      hr. As observed using light and electron microscopy, laser irradiation performed
      2.5 hr after ATX-S10 injection caused extensive vascular thrombosis with
      endothelial destruction, which persisted for at least 3 days. The proportion of
      thrombosed vessels at 6 hr after laser irradiation in the neovascular cornea
      (64+/-5%; n=3) was significantly (P<0.01) higher than that in the normal iris
      (44+/-8%; n=3). In the non-thrombosed vessels from heparinized rats, in which
      thrombosis-related ischemic effect was excluded, mitochondrial vacuolation was
      the pathologic change commonly seen in the endothelial cells, pericytes and
      neutrophils. Morphometric analysis revealed that the mitochondria of endothelial
      cells in the corneal new vessels were more severely injured than those in the
      iris vessels. The present results indicate that ATX-S10 is a potent
      photosensitizer which induces photodynamic occlusion particularly of new vessels
      probably due to the preferential biodistribution of dye in the neovascular
      tissue.

PMID- 9778413
TI  - Sulfation of intrinsic glycoproteins of the rabbit vitreous.
AB  - The experiments reported here were designed to characterize the intrinsic
      vitreous glycoproteins and to understand the process of their sulfation. Rabbits
      were injected intravitreally with 35S-sodium sulfate and killed at several time
      intervals after injection. In another series of experiments, rabbits were
      injected either with 35S-sodium sulfate, 3H-fucose or 3H-tyrosine, associated or
      not associated with tunicamycin administration. Vitreous from the control eyes
      was also digested with N-glycosidase. Furthermore, ciliary bodies, the putative
      source of the intrinsic vitreous glycoproteins, were incubated with 35S-sodium
      sulfate in the presence or absence of the protein synthesis inhibitor
      cycloheximide, and the culture media recovered for analysis. These and the
      vitreous samples of the other experiments were processed for sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and fluorography. Except
      for serum albumin, practically all polypeptide bands of the vitreous and culture
      media were labeled with radioactive sulfate and were shown to undergo renewal.
      The experiments using tunicamycin or enzyme treatment suggest that radioactive
      sulfate was incorporated not only into the carbohydrate side chains of the
      glycoproteins but also into the amino acid tyrosine of the polypeptide backbone
      of these glycoproteins.

PMID- 9778414
TI  - A novel member of the Ig superfamily, RPE7, expressed on the retinal pigment
      epithelial cell and Muller cell of the bovine retina.
AB  - The retinal pigment epithelium of the vertebrate eye plays a major part in the
      maintenance of ocular function. To identify molecules involved in the exertion of
      their physiological functions, monoclonal antibodies against bovine retinal
      pigment epithelial cells were made. Analysis by immunofluoresence and
      immunoelectron microscopy showed that one of the monoclonal antibodies named anti
      RPE7 stained the cell surface of retinal pigment epithelial cells and Muller
      cells. The anti-RPE7 antibody was revealed to recognize molecules of 45-55 kDa by
      Western blot analysis. Molecular cloning of the RPE7 cDNA and sequence analysis
      of the amino acids revealed that protein RPE7 belonged to the Ig superfamily. The
      high homology of RPE7 with metalloproteinase inducer suggests that the protein
      RPE7 might play a role in the matrix (interphotoreceptor matrix and basement
      membranes) remodeling as well as in retinal pigment epithelial cell migration
      under pathological conditions.

PMID- 9778415
TI  - Regulation of ocular mucin secretion by P2Y2 nucleotide receptors in rabbit and
      human conjunctiva.
AB  - The effects of adenine analogues on secretion of high molecular weight, mucin
      like glycoproteins (mucins) by conjunctival goblet cells were investigated using
      isolated rabbit and human conjunctiva. Mucin secretion was assayed using a
      quantitative dot-blot assay of Helix pomatia agglutinin-horseradish peroxidase
      binding to mucins absorbed to nitrocellulose filters. In rabbit conjunctiva,
      exogenous ATP (10(-7)-10(-3) m) induced a concentration-dependent, four-fold
      increase in mucin secretion that reached a plateau 15 min after drug addition.
      The rank order of potency of agonists was UTP>=ATPgammaS>ATP>ITP>ADP>>AMP.
      Adenosine, alpha,beta-methylene- ATP and beta,gamma-methylene-ATP were
      ineffective in stimulating mucin release. The response to ATP was unmodified by
      the putative P2 purinergic antagonists suramin or reactive blue (5x10(-5) m). In
      human conjunctiva, ATP and UTP were nearly equipotent in stimulating mucin
      secretion with an EC50 congruent with5x10(-6) m. These findings demonstrate that
      rabbit and human conjunctival cells contain functional P2Y2 (formerly designated
      as P2U) nucleotide receptors that govern mucin secretion. These receptors may
      provide useful pharmacological targets for therapeutic modulation of tear film
      mucins in dry-eye disorders and/or corneal wound healing.

PMID- 9778416
TI  - An ocular strain of Pseudomonas aeruginosa is inflammatory but not virulent in
      the scarified mouse model.
AB  - Pseudomonas aeruginosa is the most common pathogen among contact lens-associated
      infections. This study investigated the response of the murine cornea to
      infection with an ocular strain of P. aeruginosa isolated from a subject with an
      inflammatory adverse response to contact lens wear termed CLARE. Although this
      bacterium was isolated in confluency (greater than 2000 cfu lens-1) from the lens
      at the time of the inflammatory episode, no infection of the cornea subsequently
      developed. Male C57BL/6J mice (20 per strain) had their corneas scratched with a
      26 gauge needle (3 parallel 1.0 mm wounds in the left eye only). The incisions
      were centered over the pupillary axis and penetrated the epithelial cell basal
      lamina and into the superficial stroma. The CLARE strain was found to persist
      (viable bacteria could be cultured from corneal homogenates) up to 8 hr, as did
      the virulent control strain ATCC 19660. At 24 hr, only ATCC 19660 could be
      cultured, indicating an inability of the strain isolated from CLARE, Paer1, to
      persist in the eye consistent with the human inflammatory episode. Histological
      examination of the mouse tissue showed further differences between infection by
      the two strains. Infection with ATCC 19660 resulted in tissue necrosis and a
      large population of polymorphonuclear leukocytes (PMNs) recruited to the wound
      site. In contrast, during infection with the CLARE strain, PMN recruitment was
      reduced and temporally delayed. The CLARE strain grew as well as ATCC 19660 in
      vitro but produced less protease activity, in particular less elastase. The
      decreased PMN response and decreased protease production by the CLARE strain may
      have been responsible for the lack of ocular damage and apparent healing of the
      wound. P. aeruginosa strains are considered to be invasive or cytotoxic to
      corneal tissue, however this strain may represent a third inflammatory type
      consistent with its differing pathology.

PMID- 9778417
TI  - Mechanisms of hyperoxia-induced reductions in retinal blood flow in newborn pig.
AB  - Although reductions in retinal blood flow (RBF) in response to acute hyperoxia
      are well described, the mechanistic basis of this response has yet to be
      clarified. The present study was undertaken in order to determine the possible
      involvement of two arachidonic acid-derived vasoconstrictors, the cyclooxygenase
      metabolite thromboxane and the cytochrome P450 metabolite 20-HETE, as well as the
      involvement of the peptide endothelin and superoxide free radical. Fluorescein
      videoangiography was performed on the intact eyes of isoflurane-anesthetized
      newborn piglets. RBF responses to 20 min of hyperoxia were calculated from the
      angiograms off-line, using changes in mean arteriovenous transit times and
      arteriolar and venular diameters. The effect of hyperoxia (PaO2=351+/-9 mmHg;
      n=39) on RBF was examined in each animal under control conditions and again after
      intravitreal perivascular administration of drugs that block the synthesis or
      receptors of known vasoconstrictors. Estimated RBF decreased by a maximum of 42+/
      3% in the 7 animal groups in response to 20 min of hyperoxia. The magnitude and
      time course of the change in RBF resulting from two successive hyperoxic
      challenges did not differ, and were unaffected by intravitreal administration of
      vehicle. The response to hyperoxia was attenuated 46+/-6 (n=6; P=0.001) after
      intravitreal CGS 22652 (2 nmol), a combined thromboxane synthesis inhibitor and
      receptor antagonist. DDMS (12.5 nmol), a competitive inhibitor of the P450 enzyme
      omega-hydroxylase that forms 20-HETE, blocked hyperoxic constriction by 23+/-7%
      (n=6; P=0.01). Intravitreal pretreatment with TBC 1241z (2 nmol), a receptor
      antagonist of the peptide endothelin, blocked the hyperoxic response by 26+/-5%
      (n=6; P=0.01). A combination of CGS 22652 (2 nmol), DDMS (12.5 nmol), and TBC
      1241z (2 nmol), blocked the hyperoxic flow response by 51+/-3% (n=5; P=0.003).
      Administration of a combination of superoxide dismutase (10 U intravitreally,
      10000 U kg-1 of the polyethylene glycol-conjugate intravenously) and catalase (10
      U intravitreally, 10000 U kg-1 intravenously) was without effect on hyperoxia
      induced reductions in RBF (n=5). The present results indicate that the
      arachidonic acid metabolites thromboxane and 20-HETE, and the peptide endothelin,
      participate in mediating the acute reduction in RBF in response to hyperoxia.

PMID- 9778418
TI  - Migration of retinal microglia in experimental proliferative vitreoretinopathy.

PMID- 9778420
TI  - Announcements 

PMID- 9778419
TI  - Singlet oxygen production correlates with his and Trp destruction in brunescent
      cataract water-insoluble proteins.

PMID- 9778421
TI  - Nonlinear population dynamics: models, experiments and data.

PMID- 9778422
TI  - Assembly of exons from unitary transposable genetic elements: implications for
      the evolution of protein-protein interactions.
AB  - The discovery of "genes-in pieces" provided the first evidence that modern
      proteins evolved through the assembly and shuffling of simpler building blocks
      generally equated with exons. In the theoretical model presented here, it is
      suggested that exons were created from even smaller modules that have been termed
      duplication units. Furthermore, these segments may represent the ultimate
      building blocks for protein assembly. The nucleotide sequences of the duplication
      units to appear to resemble those mobile genetic elements such as transposons or
      insertion sequences, i.e. they possess direct repeats at each end and inverted
      sequences extending 15-25 base pairs from these direct repeats. During evolution,
      these transposable exons (trexons) would have been replicated and dispersed in
      the genome thereby promoting homologous recombination and further duplication.
      Thus, the transposition and splicing of these gene segments gave rise to
      increasingly complex proteins as well as multi-gene families of proteins. It has
      been proposed that peptides encoded by the first trexons were predisposed to form
      dimers or oligomers. Detailed structural analysis of various protein-protein
      complexes has revealed a tendency for the duplication units to self-associate.
      Self-binding peptides could have ultimately led to the evolution of protein
      ligands and receptors with high affinity.

PMID- 9778423
TI  - Modelling of allocation and balance of carbon in walnut (Juglans regia L.)
      seedlings during heterotrophy-autotrophy transition 
AB  - A deterministic and dynamic model of carbon allocation in walnut seedlings is
      described. Two experimental data sets were used to calibrate and validate the
      model. These data included: time course of the carbon content, chemical and
      isotope composition (12C and 13C) of the kernel and growing organs (roots, stem,
      leaves), and gas exchange rates during the first 55 days of the life of the plant
      with continuous 13CO2 feeding. The plant is modelled as a network with nodal
      organs acting as sources or sinks for carbohydrates. In a sink organ the demand
      for carbon is the sum of four elementary demands: maintenance respiration,
      structural growth, growth-associated respiration and carbon storage. The organs
      of the plant are assumed to be in exponential growth phase. The supply of carbon
      readily accessible for the organs is the store of soluble sugars present in a
      local reservoir. Carbon flow in the network is determined by the source/sink
      activities of the organs and local levels of demand and supply. Two carbon
      sources are considered: soluble sugars from the kernel, and gross photosynthesis.
      The rate of synthesis of soluble sugars in the kernel, and measured
      photosynthesis in the leaves are inputs for the plant model. The outputs are the
      predicted fluxes of carbon within the seedling; 13C composition,carbohydrate
      allocation to the growing organs, starch and soluble sugars accumulation, and
      respiration. The mathematical equations were translated into PSPICE software
      instructions. After optimisation of the parameter values, the model provided an
      accurate description of experimental observations in the seed-plant system during
      the critical transition from heterotrophy to autotrophy, especially C allocation
      to organs and C partitioning between storage, structural growth and respiration
      in each organ. The growth of the young plant is supply-limited, except at the
      earliest stages. A sensitivity analysis suggests that intense competition for
      carbohydrates dominates the relations among and within organs. Copyright 1998
      Academic Press Limited

PMID- 9778424
TI  - Theoretical analysis of "Switching" in a localized model for mountain pine beetle
      mass attack 
AB  - The dynamic interaction between mountain pine beetles (MPB) and hosts (generally
      lodgepole pine) is reviewed briefly. In particular, successful "switching" from
      initial foci of attack to nearby hosts which may be higher-quality resources is a
      potentially critical element initiating the transition from endemic to epidemic
      population levels. A coupled partial differential equation model for MPB
      dispersal and host response is reviewed. The equations are decoupled making an
      adiabatic assumption for MPB chemotaxis, and a "local" projection is made using
      the leading eigenfunction for the MPB density equation. This projection yields a
      system of ordinary differential equations for the spatio-temporal responses at
      individual trees. These equations are analysed to determine what factors control
      successful "switching" in a two-tree model. The results suggest that stand
      thinning ameliorates outbreaks mainly through interference with the chemical
      ecology via a change in micro-climate rather than by altering host
      vigor.Copyright 1998 Academic Press Limited

PMID- 9778425
TI  - On rugged shape of skin tumor (basal cell carcinoma).
AB  - Basal cell carcinoma (BCC) is the most common cancer of the skin that is made of
      transformed basal cells of the human epidermis, and spreads along the epidermis-
      dermis junction. It often forms tumor cell mass that protrudes towards the dermal
      connective tissue with many branches. Histopathological examination of the cancer
      demonstrates the cell mass of a rugged shape appearing as many regular spaced
      islands in a two-dimensional section. We study the process of cell proliferation
      and spatial pattern formation of the skin tumor by a pair of partial differential
      equations of tumor cells and nutrients. The assumptions are: (1) proliferation
      rate of tumor cells depends on the availability of nutrients, which simply
      diffuse out of capillaries through connective tissue; (2) nutrients are consumed
      by active tumor cells; (3) cell diffusion coefficient expressing tumor cell
      movements increase with the cell density and the nutrient availability. Starting
      from the initial condition with a single layer of tumor cells. the model develops
      a smooth colony if n'0 is large, but a characteristic rugged spatial pattern of
      tumor cell mass if n'0 is small, in which n'0 is nutrient concentration
      multiplied by square root of growth efficiency divided by diffusion coefficient
      of nutrients. The proportion of the area occupied by tumor cells increases with
      n'0. The coefficient of variation in the width of "islands" of tumor cell mass is
      rather small (0.2 reverse similar0.6), implying the regularity of the spatial
      pattern. We also analyses the photographs of a two-dimensional section of tumor
      cell mass and compare the spatial patterns generated by the model.

PMID- 9778426
TI  - Pattern formation in a patch occupancy metapopulation model: a cellular automata
      approach.
AB  - The explicit consideration of space in ecological research is of paramount
      importance to understand the structure and functioning of ecological systems. In
      this paper we develop a simple spatially explicit metapopulation model in which
      colonization is constant and independent of the number of occupied patches (i.e.
      propagule-rain effect, Gotelli, 1991). Extinction, on the other hand, is modelled
      as a stochastic process whose intensity depends on the number of occupied patches
      in the neighborhood of each focal patch. Our model is the CA counterpart of two
      classical patch occupancy metapopulation models. We analytically prove this by
      showing that our CA converges to the differential equation in the mean-field
      approximation. The asymptotic behaviour of the system, expressed as the
      proportion of occupied patches, agrees with the equilibrium proportion of patches
      derived by using ODEs. In both models, the existence of a rescue-effect increases
      the range of extinction and colonization parameters over which the system attains
      complete occupancy of patches. However, in our model this result is strongly
      influenced by the degree of coupling among patches and is apparent only for local
      interactions. With local interactions and particular parameter values of
      colonization and extinction, self-organized spatio-temporal patterns emerge with
      a fractal-like clustering, even though the environment is spatially homogeneous.
      Our results point out that the importance of being spatial and discrete (Durrett
      & Levin, 1994a) in our model is a result of local interactions.

PMID- 9778427
TI  - On the concept of leaf boundary layer resistance for forced convection 
AB  - The definition of leaf boundary layer resistance is reconsidered in respect of
      the three-dimensional diffusion-controlled mass transport region just above the
      leaf surface. Due to the existence of this superstomatal air layer, the
      conventional convective boundary layer is not in direct contact with the surface.
      Thus, in terms of plant physiology, the diffusive "end correction" to the
      stomatal resistance should be included in the boundary layer resistance. This is
      true for laminar as well as turbulent flows. When the surface mole fraction of an
      exchanged gas is estimated using the boundary layer resistance ignoring the
      diffusive term may lead to a noticeable error. The self-consistent approach is
      used to clarify the problems of the boundary layer formation and stomatal
      interference. If the correction is taken into account, the boundary layer
      resistance becomes dependent also on stomatal shape and distribution on the leaf.
      The traditional semiempirical formula corrected by the superstomatal diffusion is
      applied in numerical calculations. In estimates of the water vapour mole fraction
      on the surface of a transpiring leaf the relative error ranges from insignificant
      (quiescent air, large leaf and large stomatal pores) to 20 % (low humidity,
      strong wind, small leaf and small elliptic pores). The boundary layer resistance
      can decrease by a factor of 3 when the semiaxis lengths of the stomata increase
      from 1 and 0.5 &mgr;m to 10 and 5 &mgr;m. The effective thickness of the
      superstomatal air layer is maximally several millimetres (small stomatal surface
      concentration and small pores). Copyright 1998 Academic Press Limited

PMID- 9778428
TI  - Score-dependent fertility model for the evolution of cooperation in a lattice.
AB  - The evolution of cooperation is studied in a lattice-structured population, in
      which each individual plays the iterated Prisoner's Dilemma game with its
      neighbors. The population includes Tit-for-Tat (TFT, a cooperative strategy) and
      All Defect (AD, a selfish strategy) distributed over the lattice points. An
      individual dies randomly, and the vacant site is filled immediately by a copy of
      one of the neighbors in which the probability of colonization success by a
      particular neighbor is proportional to its score accumulated in the game. This
      "score-dependent fertility model" (or fertility model) behaves very differently
      from score-dependent viability model (viability model) studied in a previous
      paper. The model on a one-dimensional lattice is a analysed by invasion
      probability analysis, pair-edge method mean-field approximation, pair
      approximation, and computer simulation. Results are: (1) TFT players come to form
      tight clusters. When the probability of iteration w is large, initially rare TFT
      can invade and spread in a population dominated by AD, unlike in the complete
      mixing model. The condition for the increase of TFT is accurately predicted by
      all the techniques except mean-field approximation; (2) fertility model is much
      more favorable for the spread of TFT than the corresponding viability model,
      because spiteful killing of neighbors is favored in the viability model but not
      in the fertility model; (3) eight lattice games on two-dimensional lattice with
      different assumptions are examined. Cooperation and defects can coexist in the
      models of deterministic state change but not in the models of stochastic state
      change.

PMID- 9778429
TI  - Are only repeated triplets guilty?
AB  - It is well known that in some places of the human genome one finds a variable
      number of tandem repeats of trinucleotides; it is now commonly acknowledged that
      in many cases an excessive expansion of such a number is the cause of nervous
      system diseases. Moreover there exist cases of genetic disorders linked with loci
      where a variable number of tandem repeats of sequences longer than three bases
      has been found. The abnormal number of these repeats in few cases has been
      associated with the onset of the disease. Considering the above facts, we have
      performed an extensive study of published sequences of genes connected with
      various diseases. We have examined, inside or near those genes, all possible
      tandem repeats. The analysis has led to the detection of a large number of
      repeats of both triplets and longer sequences, many of which, as far as we know,
      had not been pointed out before. The results of our analysis lead us to put
      forward the hypothesis that in more cases than those till now established, a
      variable number of tandem repeats of generic sequences, not only of triplets,
      could be associated with disease onset. Finally we suggest to allocate
      experimental researches for all the possible tandem repeats and their possible
      correlation with the neurodegenerative disorders and with other kinds of
      syndromes.

PMID- 9778430
TI  - Evolutionarily stable mutation rates.
AB  - I investigate the hypothesis that mutation rates in natural populations are
      determined by a balance between: (1) selection against deleterious mutations
      favouring lower mutation rates, and (2) selection opposing further reduction of
      the mutation rate, resulting from the costs incurred by more stringent proof
      reading and repair (for example, a reduction in the rate of DNA replication). The
      influence of advantageous mutations is assumed to be negligible. In a previous
      paper, I analysed the dynamics of a modifier of the mutation rate in a large
      sexual population, where (infinitesimally rare) deleterious alleles segregate at
      an infinite number of unlinked loci with symmetric multiplicative fitness
      effects. A simple condition was obtained for a modifier allele to increase in
      frequency. Remarkably, this condition does not depend on the allele frequencies
      at the modifier locus. Here, I show that (as a consequence), given any set of
      possible values of the mutation rate (any set of possible modifier alleles),
      there always exists a single globally stable value of the mutation rate. This is
      an unusually strong form of "evolutionary stability" for a sexual population.
      Less surprisingly the optimum mutation rate in an asexual population has similar
      stability properties. Furthermore, in the case of an asexual population, it is
      not necessary to make any special assumptions about the selection acting against
      deleterious mutations, except that a deterministic mutation-selection equilibrium
      exists. I present a simple method for identifying the evolutionarily stable value
      of the mutation rate, given the function alpha(U) relating the value of the
      mutation rate to the fitness cost of maintaining this rate. I also argue that if
      there is a highly conserved relationship between the rate of replication per
      base, and the rate of mutation per base, and if this relationship has the form of
      a power law, then the remarkable uniformity of the per genome mutation rate in
      DNA based microbes can be explained.

PMID- 9778432
TI  - Role of enzyme-substrate flexibility in catalytic activity: an evolutionary
      perspective.
AB  - Site-directed mutagenesis has proved an effective experimental technique to
      investigate catalytic mechanisms and to determine relations between enzyme
      structure and function. This article invokes an analytical model based on
      evolution by mutation and natural selection-Nature's analogue of site-directed
      mutagenesis-to derive a set of general rules relating enzyme structure and
      activity. The catalysts are described in terms of the structural parameters,
      rigidity and flexibility, and the functional variables, reaction rate and
      substrate specificity. The evolutionary model predicts the following structure
      activity relations: (a) rigid enzyme-flexible substrate: large variation in
      reaction rates, broad substrate specificity; (b) rigid enzyme-rigid substrate:
      diffusion controlled rates, absolute specificity; (c) flexible enzyme-rigid
      substrate: intermediate reaction rates, group specificity; (d) flexible enzyme
      flexible substrate: slow rates, absolute specificity. Spectroscopic methods and X
      ray crystallography now yield important characteristics of enzyme-substrate
      complexes such as molecular flexibility. The evolutionary analysis we have
      exploited provides general principles for inferring catalytic activity from
      structural studies of enzyme-substrate complexes.

PMID- 9778431
TI  - Integral rein control in physiology.
AB  - We propose that blood glucose is regulated by a principle which we call integral
      rein control, in which under most conditions both glucagon and insulin are
      produced and control is achieved by altering the balance between the two. Like
      other integral control systems, the mechanism achieves zero steady-state error,
      which explains how the blood glucose level can remain very nearly constant over a
      wide range of input and demand. In addition, the use of two hormones makes the
      system stable against relatively large perturbations in either direction. An
      important feature of the model is that the set point is not fixed by an external
      reference but arises out of the dynamics, in particular out of the relation
      between the rates of production of the two hormones. The model therefore predicts
      that the consequence of an inability to produce insulin will be not just that the
      control will be less effective but that the set point will be shifted. This
      allows us to explain why patients with untreated Type I diabetes mellitus have
      high blood glucose levels even under conditions of low glucose input, and why it
      is difficult to maintain the normal level of 5 mmol/1 in patients who are being
      treated with insulin. It also explains why Type II diabetes is easier to treat.

PMID- 9778433
TI  - The evolution of diapause in a coupled host-parasitoid system.
AB  - Diapause of part of a population during a breeding opportunity is widespread
      among insects. We explore the evolution of such diapause in a coupled host
      parasitoid system, using a discrete-generation population dynamic model that
      incorporates diapause. We show that diapause in the host tends to be a
      stabilizing factor while diapause in the parasitoid does not affect the stability
      boundaries. We then allow the frequency of diapause in the host and parasitoid to
      evolve, and find the joint population and evolutionary dynamic equilibrium by
      numerical methods. At the equilibrium, population dynamics exhibit cycles and
      host diapause always occurs. Parasitoid diapause often occurs, though this
      depends on exact parameter values. Thus, intrinsically generated fluctuations in
      fitness (due to cyclical population dynamics) lead to the evolution of diapause
      as a bet-hedging mechanism.

PMID- 9778434
TI  - Self-reproducing system can behave as Maxwell's demon: theoretical illustration
      under prebiotic conditions.
AB  - The recent discovery of polymerase activity in a ribosomal RNA intervening
      sequence as well as other studies of RNA-replicating systems suggest that the
      first living molecules were RNAs called replicases. According to this suggestion
      from biochemical studies, the replicase system is chosen as the simplest case of
      self-reproducing systems, and the fundamental problem of "what is life" is
      theoretically investigated by analysing the behavior of a replicase system with a
      supply of organic materials under prebiotic conditions. In this analysis, it is
      essential to consider (i) self-reproduction on the basis of its own information,
      (ii) maintenance and improvement of the information by selection and (iii)
      environmental event of non-biologically generating organic materials from
      inorganic matter by photochemical reactions, probably occurring in prebiotic
      conditions on the Earth. The replicases can retain and further elevate their self
      reproducibility through competition among their descendant mutants for acquiring
      a limited quantity of materials, if the initial ability of self-reproduction and
      the concentration of replicases are above some critical values. By this
      selection, the replicase molecules retain a narrowed range of nucleotide
      sequences, or a state of lower entropy, against the natural tendency of sequence
      divergence, but this entropy reduction is sufficiently compensated by the entropy
      production in the environmental event of energy conversion from photons to heat.
      Once the stability of a self-reproducing system is established in the above
      sense, the self-reproducing system can operate as Maxwell's demon to regulate the
      outside flow of matter by its catalytic function without any contradiction to the
      second law of thermodynamics.

PMID- 9778435
TI  - Errors associated with metabolic control analysis. Application Of Monte-Carlo
      simulation of experimental data.
AB  - The errors associated with experimental application of metabolic control analysis
      are difficult to assess. In this paper, we give examples where Monte-Carlo
      simulations of published experimental data are used in error analysis. Data was
      simulated according to the mean and error obtained from experimental measurements
      and the simulated data was used to calculate control coefficients. Repeating the
      simulation 500 times allowed an estimate to be made of the error implicit in the
      calculated control coefficients. In the first example, state 4 respiration of
      isolated mitochondria, Monte-Carlo simulations based on the system elasticities
      were performed. The simulations gave error estimates similar to the values
      reported within the original paper and those derived from a sensitivity analysis
      of the elasticities. This demonstrated the validity of the method. In the second
      example, state 3 respiration of isolated mitochondria, Monte-Carlo simulations
      were based on measurements of intermediates and fluxes. A key feature of this
      simulation was that the distribution of the simulated control coefficients did
      not follow a normal distribution, despite simulation of the original data being
      based on normal distributions. Consequently, the error calculated using
      simulation was greater and more realistic than the error calculated directly by
      averaging the original results. The Monte-Carlo simulations are also demonstrated
      to be useful in experimental design. The individual data points that should be
      repeated in order to reduce the error in the control coefficients can be
      highlighted.

PMID- 9778436
TI  - Satiety splits feeding behaviour into bouts 
AB  - Animal behaviour is frequently displayed in bouts. Bout analysis aims at finding
      a bout criterion, i.e. that time between events that separates intervals within,
      from intervals between, bouts. Methods used for quantitative bout analysis are
      log-supervivorship and log-frequency analysis. Both models assume that the
      probability of the start of an event (or a bout) is independent of the time since
      the last event (or bout) and that, therefore, events as well as bouts occur
      according to Poisson processes, i.e. purely at random. The frequencies of
      intervals within, as well as between, bouts are then distributed as negative
      exponentials. These models are also widely applied in feeding behaviour analysis,
      where bouts can be meals. However, the satiety concept predicts that after
      terminating a meal, the animal's feeding motivation will be low. The probability
      of the animal initiating the next meal is expected to increase with time since
      the last meal and, therefore, meals will not likely be randomly distributed. A
      negative exponential is then not the most appropriate model to describe the
      frequency distribution of intervals between meals. Results of an experiment in
      which feeding behaviour of 16 cows was recorded continuously for 30 days were
      used to test the suitability of existing bout analysis techniques. It is
      concluded that these techniques are inadequate for the description of the
      observed interval distributions. A new model is proposed that takes account of
      the observed "shortage" of short intervals between meals. In contrast to existing
      models, that describe log-transformed frequency distributions of interval
      lengths, the proposed model describes frequency distributions of log-transformed
      interval lengths. Compared with existing models, this log-normal model is in
      better agreement with the biological phenomenon of satiety, it gave a better fit
      to the observed interval distribution and led to a more meaningful meal
      criterion.Copyright 1998 Academic Press Limited

PMID- 9778437
TI  - Sperm competition games: a general approach to risk assessment.
AB  - We investigate game theory models of ejaculate expenditure by males in a species
      where there is a risk probability, q, that females will mate twice before laying
      a given set of eggs. With frequency 1-q females mate just once; then males
      optimally ejaculate an arbitrary minimum amount of sperm. The paper extends the
      analysis of Parker et al. (1997) in which males have limited information about
      the three risk states of the female: 0 (virgins which will mate now but not
      again), 1 (virgins which will mate now and then once more), and 2 (once-mated
      females who will mate now but not again). We derive a general structure for
      finding ESSs under imperfect information about states, and examine two special
      cases in which males know the overall risk probability q, but have imperfect
      knowledge of the states (0, 1, 2). In Case 1, males cannot distinguish between
      states 0 and 1 but have limited information about state 2. As their information
      increases, so does the difference in sperm allocation, with more going to females
      assessed as mated (state 2) than to females assessed as virgins (0, 1). This
      difference decreases with q in a species, but the average ejaculate expenditure
      increases with q. Even for small amounts of information, the behaviour as q-->0
      is different from that predicted for zero information. In Case 2, males have
      perfect information about state 2, but limited information about states 0, 1.
      This has a major effect if q is small: males effectively behave as if they had
      perfect information by giving equal amounts of sperm to females assessed as 1 as
      those assessed to be 2, while giving a minimum amount to females assessed as 0.
      Ejaculate expenditures generally increase with the overall species-level risk q.
      A result common to both cases is that even a small amount of information allows
      more strategic choice than the zero information case and hence qualitatively
      different behaviour.

PMID- 9778438
TI  - Hysteresis-driven structure formation in biochemical networks 
AB  - A mechanism of structure formation, based on hysteresis behaviour is presented. A
      bisubstrate kinetic system with substrate inhibition, discussed previously in the
      context of Turing structure formation, may show hysteresis behaviour, when
      embedded in a metabolic network: the system may possess multiple steady states
      and may be switched from one stable fixpoint to the other. When cells containing
      this type of system are diffusively coupled, under certain conditions patterns
      result, which, as is demonstrated, are not of the Turing type. The main
      difference to diffusion-driven (Turing) structures is the fact that the
      hysteresis-driven patterns emerge under diffusive conditions, under which both
      the homogeneous and the asymmetrical steady state is stable. The resulting
      special properties and biological implications are discussed.Copyright 1998
      Academic Press Limited

PMID- 9778439
TI  - Why is meiosis arrested?
AB  - In mammals and birds, females are born with all the oocytes required for future
      ovulations. These oocytes are not haploid: they are arrested at the Prophase I of
      meiosis when they have two sister chromatids of each chromosome (i.e. the eggs
      are at the 4C stage). Under the assumption that the low number of ovulated eggs
      in these species have been selected to be of high quality, I propose three
      explanations for these two observations: (I) producing the eggs before birth may
      decrease the variance in mutations and genetic damage, thereby reducing risk;
      (II) arresting the oocytes at a 4C stage may allow sister-strand recombination to
      repair genetic damage; (III) arresting the oocytes at the 4C stage may mitigate
      intergametic conflict, hence potential selection of the oocytes for ovulation
      will not involve conflict. Predictions from the Mutational, Repair, and Conflict
      Hypotheses are critically evaluated in the light of unpublished data,
      evolutionary theory, and computer simulations.

PMID- 9778441
TI  - A double circadian oscillator model for quantitative photoperiodic time
      measurement in insects and mites 
AB  - From studies on photoperiodic time measurement in insects it is known that
      different night lengths at the same side of the critical night length can have
      different inductive strengths. This means that nights of different length, and
      either longer or shorter than the critical night length, can have qualitatively
      different values. Nevertheless, few photoperiodic-clock models have been
      developed that are based on quantitative night-length measurement. In this paper
      a model is proposed that consists of two independent, circadian mechanisms. Both
      mechanisms determine the length of a night and give it a quantitative value,
      which is either zero or positive. One of the mechanisms (LN system) generally
      gives a scotophase a positive value when it is "long" (i.e. lights-on occurs when
      the LN oscillator is in its descending phase), whereas the other (SN system)
      gives a scotophase a positive value when it is "short" (i.e. lights-on occurs
      when the SN oscillator is in its ascending phase). In this particular context,
      therefore, "long" and "short" do not necessarily mean longer or shorter than the
      critical night length. The reasons for two time-measuring systems instead of one
      are: first, in some insects only long nights are accumulated, not short nights,
      or vice versa. Second, long nights are less sensitive to temperature than short
      nights. Third, in some cases it seems that long and short nights are determined
      in a different manner. These observations indicate that long and short nights
      could be determined by separate mechanisms. Responses generated by the proposed
      model parallel those observed experimentally with the spider mite, Tetranchus
      urticae and the aphid, Megoura viciae. General properties of the model are
      discussed and compared with Zaslavski's quantitative clock model which shares
      some features. Copyright 1998 Academic Press Limited

PMID- 9778440
TI  - Risky choice and Weber's Law.
AB  - We present a family of models of choice between behavioural alternatives with
      stochastic outcomes (risky choice) based on the effects of Weber's Law in memory.
      These models generalise and extend a model of risk sensitive foraging originally
      proposed by Reboreda & Kacelnik [(1991) Behav. Ecol. 2, 301-308], which yielded
      qualitative predictions (risk-aversion for amount of food and risk-proneness for
      delay to food). We now demonstrate how this approach can predict quantitatively
      the partial preferences between two alternative options with any mean and
      variance in their outcomes, and the certainty equivalent of an option consisting
      of any set of probabilistic outcomes. The approach is also relevant to the
      economics and psychology of risk sensitivity because it predicts risk aversion
      for any desirable outcome (such as monetary gains) and risk seeking for any
      undesirable gain (such as monetary losses). Our models are process-based rather
      than purely normative, and are based on linear expected utility as a function of
      expected outcomes. They do not account for all observed aspects of risky choice,
      but their descriptive performance betters that of existing functional models and
      requires fewer parameters.

PMID- 9778442
TI  - The dynamics of drug action on the within-host population growth of infectious
      agents: melding pharmacokinetics with pathogen population dynamics.
AB  - The use of simple mathematical models to study the kinetics of drug action and
      decay within vertebrate hosts has a long history with a major objective being to
      derive drug dosage regimens that optimize efficacy and minimize toxicity to the
      patient. Mathematical models of the relationship between dosage, route of
      delivery, drug concentration in defined sites and effect on a particular pathogen
      are widely used in the pharmacological literature. A more recent literature is
      that concerned with the population dynamics of pathogen replication within the
      host subjected to pressures exerted by the human immune system. In this paper we
      develop a theoretical framework to meld both approaches with the aim of
      identifying threshold criteria that dictate the optimum pattern of drug
      administration for pathogen clearance from the host. In particular we show how
      the percentage reduction in microparasite abundance is related to the
      pharmacokinetic parameter, AUC, recording the area under the drug concentration
      time curve within the treated patient, in terms of the parameters that define the
      population dynamics of the pathogen and the properties of the drug. Two
      particular pathogens are examined to illustrate the principles underpinning the
      dynamics of the pharmacokinetic-population dynamic models, namely HIV and
      Plasmodium falciparum. Criteria for pathogen persistence or elimination are
      derived for these specific models based on the definition of a basic reproductive
      number, R0, which measures the average number of secondary infected target cells
      in a host generated by a single infected cell (CD4 lymphocyte for HIV, and
      erythrocyte for P. falciparum) within a population of susceptible cells. For the
      pathogen to invade the host and persist over time, R0</=1. Under chemotherapeutic
      regimens, expressions for R0 are derived allowing estimates to be made of the
      ideal treatment regime required to eliminate the pathogen, both for HIV and P.
      falciparum malaria.

PMID- 9778443
TI  - The humoral immune response to Haemophilus influenzae type b: a mathematical
      model based on T-zone and germinal center B-cell dynamics.
AB  - Through careful mapping of the physiology of the T-zone and GC B-blast dynamics
      to a mathematical representation of the cell processes including proliferation,
      migration, differentiation, and cell death, a mathematical model is constructed
      to capture the dominant nominal primary, late follicular, and secondary humoral
      response to Haemophilus influenzae Type b. This model explicitly incorporates the
      dynamics of memory B-cells, T-zone and GC B-dynamics, IgM and IgG antibodies,
      avidity maturation, and IC presentation by FDCs into a coherent framework. This
      paper describes the relevant immunology, the pertinent physiological assumptions,
      the developed model, and the parameter identification procedure. The model
      parameters were found using a parameter identification procedure that capitalizes
      on the timing and interactions of certain dominant physiological attributes.
      Simulation results and validation tests indicate that the model reflects not only
      a nominal primary and secondary humoral immune response but also the tertiary and
      T-independent responses. The model shows robustness to variations in infection
      dosage, bacterial growth rate (virulence of the strain), and onset-timing of the
      secondary response. The utility of this model in studying the humoral immune
      response is demonstrated through suggested physiological assumptions, mechanisms,
      and rates to be eventually clinically evaluated as well as insights into
      vaccination design. The model and parameter identification techniques are easily
      adapted to other diseases which primarily evoke a humoral immune response.

PMID- 9778444
TI  - Individual sex preferences and the population sex ratio of newborns.
AB  - This paper proposes the hypothesis that countries with stronger sex preferences
      are more likely to have a negative relationship between crude birth rates and
      male/female ratios of newborn babies. Conversely, the existence of a
      significantly negative relationship in any country may also be a supportive
      evidence of its preferences for sons. Our hypothesis is both behavioral and
      biological: on the behavioral side, parents with strong sex preferences are
      inclined to continue to bear children if the existing sex ratio of children is
      less than desirable. On the biological side, parents with many girls are more
      likely to be "girl producers", who with individual-specific biological
      characteristics tend to generate higher female births. We use the macro data in
      the United Nations Demographic Yearbook to verify and test our hypothesis. For
      developing countries which do not have reliable micro data on fertility, our
      approach using macro data is a useful and interesting alternative.

PMID- 9778445
TI  - Unifying genetic and game theoretic models of kin selection for continuous
      traits.
AB  - A framework is presented for unifying single locus genetic and game theoretic
      models of continuous traits under frequency-dependent selection when there are
      interactions among relatives. This framework serves two purposes. First, it is
      used to determine how "games between relatives" must be modeled to be genetically
      valid. There are two commonly employed phenotypic approaches used in this
      setting, and we demonstrate that, although some of their predictions are always
      genetically valid, others are invalid in general, and this is true for both
      haploid asexual and diploid sexual organisms. In particular, we show that both
      approaches obtain the correct equilibrium and convergence stability conditions,
      but neither obtains the correct condition for evolutionary stability. Unlike
      earlier results for discrete trait matrix games (Hines & Maynard Smith, 1979),
      there is no simple correspondence between phenotypic and genetic predictions, and
      we provide two examples to illustrate this point. It is possible however, to
      obtain these earlier results within the present setting by restricting attention
      to a particular class of fitness functions. These results demonstrate that, even
      when selection is weak, phenotypic models can fail if fitness is frequency
      dependent. The second purpose is to determine when population mean inclusive
      fitness effect provides an adaptive topography in games between relative. Our
      results show that the fitness function must have a special form for this to be
      true, and this form differs between haploid and diploid organisms.

PMID- 9778446
TI  - Theoretical maximal flow of the left ventricle is sensitive to change in
      ventricular afterload.
AB  - Systolic mechanical behavior of the ventricular pump can be quantified by both
      maximal systolic elastance and theoretical maximal flow. How sensitive these two
      model parameters are to changes in loading conditions has never been examined,
      however. The aim of the study is to determine the roles of these two parameters
      in the perturbation of ventricular loads. The loading conditions are altered by
      the use of methoxamine, a specific alpha1-selective adrenergic agonist. Left
      ventricular pressure and ascending aortic flow waves in male Fischer 344 rats are
      measured by a high-fidelity pressure sensor and electromagnetic flow probe,
      respectively. Isovolumetric pressure of the left ventricle is estimated from the
      instantaneous pressure of an ejecting contraction by a curve-fitting technique.
      The two parameters that characterize systolic pumping mechanics of the left
      ventricle are inferred by making use of an elastance-resistance model. Results in
      this study show that the theoretical maximum flow, the amount of outflow
      generated by the ventricle if it were to eject under zero load condition, is
      sensitive to change in ventricular afterload. On the contrary, the maximal
      systolic elastance is independent of loading conditions in a given constant
      contractile state of the ventricle. It is believed that afterload-dependent
      behavior of the theoretical maximal flow is the major factor responsible for the
      poor predictive performance of the elastance-resistance model.

PMID- 9778447
TI  - Structural resolution of the folding pathway of a protein by correlation of phi
      values with inter-residue contacts.
AB  - Folding of barstar, the 10 kDalton inhibitor of the ribonuclease barnase, has
      been suggested to follow a nucleation-condensation model [Nolting, B., Golbik,
      R., Neira, J. L., Soler-Gonzalez, A. S., Schreiber, G. & Fersht, A. R. (1997).
      Proc. Nat. Acad. Sci. U.S.A. 94, 826-830], where structure growth starts in a
      particular region of the molecule, the folding nucleus. Here the structure of the
      diffuse nucleus and its growth in three stages, 500 micros, 1 ms and 100 ms after
      initiation of the folding reaction, is mapped out by using phi-values which are
      correlate with inter-residue contact plots. Barstar folding is initiated by a
      significant consolidation of interactions in and around the strand1-loop1-helix1
      motif in the microsecond time scale, followed by the consolidation of helix4,
      which is located close to the C-terminus and does not have significant residual
      structure in the cold-denatured state. The non-uniform structure consolidation is
      most pronounced in the early stages of folding. The late folding events of
      barstar are characterized by a propagation of structure consolidation from the N
      and C-termini towards residues located in the center of the sequence.

PMID- 9778449
TI  - Hierarchical organization and the structural-interactive hierarchy.

PMID- 9778448
TI  - Fertility and labour supply in Femina economica.
AB  - This paper sets out a formal framework for the biological-evolutionary study of
      human economic behaviour. Femina economica is a hypothetical parthenogenetic
      species with a simple economy. Individuals make decisions about labour supply and
      fertility subject to time and resource constraints. Labour is of differing types
      and a parent determines the type of her offspring's labour. Wages are determined
      as marginal productivities from an economy-wide production function. Three
      propositions are proved, of which the first shows that under very general
      conditions there exists a population genetic equilibrium, in which individuals'
      decisions are assumed to be under genetic control. The second shows that at a
      population genetic equilibrium, individuals have the same behaviour as they would
      at an economic equilibrium, in which individuals are assumed to maximise a common
      utility function. The third proposition shows that if the common utility function
      fulfils certain conditions, the attainment of an economic equilibrium brings
      about the same behaviour as a population genetic equilibrium. This suggests a way
      in which evolutionarily stable behaviour can be brought about without the
      necessity for changes in gene frequencies. Demographic implications include the
      possibility of interpreting in Darwinian terms the reductions in offspring number
      that occur in fertility transitions, and the weak or even negative correlation in
      economically developed societies between control of resources and offspring
      number. There are implications for economics of deriving utility maximisation
      from population genetics.

PMID- 9778450
TI  - The construction and use of a PCR internal control.
AB  - An example of the application and contruction of a polymerase chain reaction
      (PCR) internal control is presented. The internal control is synthesized in one
      PCR reaction. The primers used in this reaction possess 5' over-hanging ends
      which are identical to the primers used in the diagnostic reaction, whereas their
      3' ends are complementary to a predetermined DNA sequence (pUC19 in this case) of
      defined length and sequence. As the sequence of the control except for primer
      sites, is not homologous to the PCR signal product, the formation of
      heteroduplexes and non-specific PCR products should not occur. Neither is there a
      risk that the target DNA will contaminate the internal control. However, the
      simultaneous amplification of two different DNA fragments flanked by the same
      primer sites resulted in either inhibition or enhancement of one or both products
      depending on the molar ratio of those DNA fragments. The presented method may be
      applied to construction of internal controls for quantitative PCR. The internal
      control was developed and tested for use in a PCR detection system for
      Agrobacterium tumefaciens.

PMID- 9778451
TI  - Cytochrome P450 2E1 mRNA in the rat prostate: detection and quantitation by
      competitive reverse transcription and polymerase chain reaction.
AB  - Cytochrome P450 2E1 plays a pivotal role in the metabolic activation of a wide
      variety of low molecular weight environmental toxicants and procarcinogens. In
      the present study, expression of the P450 2E1 gene in the rat prostate gland was
      quantitated by competitive reverse transcription and the polymerase chain
      reaction. To assess accurately the induction level of P450 2E1 mRNA in the
      prostate after pyridine treatment of rats, a recombinant standard RNA was
      generated that is homologous to the sequence of P450 2E1 mRNA except for an
      internal deletion of 100 bases. The data indicate that P450 2E1 mRNA is present
      in the prostate of untreated animals and is induced about four-fold by treatment
      with pyridine. The results suggest that exposure to certain environmental
      chemicals and procarcinogens may increase P450 2E1 levels in the prostate gland
      and thus could enhance formation of reactive, carcinogenic metabolites.

PMID- 9778452
TI  - Detection and quantification of the A3243G mutation of mitochondrial DNA by
      ligation detection reaction.
AB  - The A3243G mutation of mitochondrial DNA is associated to the MELAS syndrome and
      to transmitted forms of diabetes mellitus. This mutation exists in a
      heteroplasmic state and can be present at a minor and hardly detectable level.
      The aim was to design a method which could be applied to large series of samples
      and could provide rapid, sensitive and quantitative detection of this mutation in
      the wild-type mitochondrial DNA background. The ability of ligation detection
      reaction (LDR) to satisfy these objectives was evaluated. Ligation detection
      reaction was performed on a model template composed of mixtures of various
      proportions of plasmids bearing the wild-type or mutant mitochondrial DNA
      sequence. Radiolabelled or fluorescent primers and the wild-type and mutant LDR
      products were separated by electrophoresis on conventional denaturating gel or on
      an Applied Biosystem 373. The ratios of mutant/wild-type products were consistent
      with the initial ratios of the plasmids in the template. The sensitivity and
      accuracy of the fluorescence and isotopic detection methods were similar. The
      detection limit of mutant DNA was 10% of total mitochondrial DNA. The percentage
      of mutant DNA in DNA samples extracted from leukocytes of 19 patients having the
      mutation at different levels, was evaluated by fluorescent or isotopic LDR.

PMID- 9778453
TI  - Semi-quantitative RT-PCR for comparison of mRNAs in cells with different amounts
      of housekeeping gene transcripts.
AB  - A simple method is reported here for the semi-quantitative assay of mRNAs in the
      presence of an exogenous mRNA (pBR322 transcript) as a standard. This method uses
      the co-reverse transcription and co-amplification (co RT-PCR) of the target and
      standard mRNAs. This procedure enables transcripts to be compared when the
      differentiation process affects the transcription pattern of the beta-actin
      housekeeping gene, a commonly used internal standard. This method is sensitive
      and avoids constructing internal competitive RNA standards. As an example, it is
      shown that beta-actin transcription decreases and type V adenylyl cyclase
      transcription increases in adipocytes, when compared to preadipocytes.

PMID- 9778455
TI  - Multiplex PCR for the detection of Mycoplasma fermentans, M. hominis and M.
      penetrans in cell cultures and blood samples of patients with chronic fatigue
      syndrome.
AB  - A multiplex polymerase chain reaction (PCR) was initially developed to detect the
      presence of mycoplasma genus DNA sequences in cell cultures and to differentiate
      between three human pathogenic mycoplasma species simultaneously. The assay in
      turn, proved to be a useful tool for the detection of mycoplasma infection in
      human DNA samples. One set of oligonucleotide primers which are specific for a
      highly conserved region among all members of the genus mycoplasma along with
      three other primer sets which are specific for Mycoplasma fermentans, Mycoplasma
      hominis andMycoplasma penetrans species were used in this assay. The sensitivity
      of detection was determined by infecting peripheral blood mononuclear cells
      (PBMC) of healthy individuals with known bacterial copy numbers from each
      species, extracting the DNA, and subjecting 1 microgram of DNA from each sample
      to 40 cycles of amplification. By using agarose gel electrophoresis the detection
      level was determined to be 7, 7, 9 and 15 mycoplasma cells per microgram of human
      genomic DNA for M. genus,M. fermentans, M. hominis and M. penetrans,
      respectively. The assay was applied to DNA extracted from the PBMCs of
      individuals suffering from chronic fatigue syndrome (CFS) (n=100) as determined
      by the Center for Disease Control (CDC) criteria, and compared to healthy
      individuals (n=100). The percentage of M. genus infection was found to be 52% in
      CFS patients and only 15% in healthy individuals. Mycoplasma fermentans, M.
      hominis andM. penetrans were detected in 32, 9 and 6% of the CFS patients while
      they were detected in 8, 3 and 2% of the healthy control subjects, respectively.
      This assay provides a rapid and cost efficient procedure to screen either cell
      cultures or clinical samples for the presence of three potentially pathogenic
      species of mycoplasma with a high level of sensitivity and specificity.

PMID- 9778454
TI  - Molecular analysis reveals a high mutation frequency in the first untranslated
      exon of the PPOX gene and largely excludes variegate porphyria in a subset of
      clinically affected Afrikaner families.
AB  - A subset of probands from 11 South African families with clinical and/or
      biochemical features of variegate porphyria (VP), but without the known
      protoporphyrinogen oxidase (PPOX) gene defects identified previously in the South
      African population, were subjected to mutation analysis. Disease-related
      mutation(s) could not be identified after screening virtually the entire PPOX
      gene by heteroduplex single-strand conformation polymorphism analysis (HEX-SSCP),
      although three new sequence variants were detected in exon 1 of the gene in three
      normal controls. The presence of these single base changes at nucleotide
      positions 22 (C/G), 27 (C/A) and 127 (C/A), in addition to the known exon 1
      polymorphisms I-26 and I-150, indicates that this untranslated region of the PPOX
      gene is particularly mutation-prone. Furthermore, microsatellite markers flanking
      the PPOX and alpha-1 antitrypsin (PI) gene, on chromosomes 1 and 14,
      respectively, were used to assess the probability of involvement of these loci in
      disease presentation. Common alleles transmitted from affected parent to affected
      child were determined where possible in the mutation-negative index cases.
      Allelic frequencies of these <<disease-associated>> alleles were compared to
      findings in the normal population, but no predominant disease-associated allele
      could be identified. Co-segregation of a specific haplotype with the disease
      phenotype could also not be demonstrated in a large Afrikaner family. It is
      concluded that further studies are warranted to determine the genetic factor(s)
      underlying the autosomal dominant pattern of inheritance in molecularly
      uncharacterized cases showing clinical symptoms of an acute porphyria.

PMID- 9778456
TI  - Non-radioactive detection of K-ras mutations by nested allele specific PCR and
      oligonucleotide hybridization.
AB  - The development of methods to detect point mutations has been rapid over the
      recent years. In human colon tumours, a significant percentage of mutations are
      found in the K-ras gene. Faster and more sensitive methods for detection of these
      mutations are important for patient management and treatment. The author has
      extended the specificity of allele amplification of point mutations by using
      mismatch oligonucleotide primers in a polymerase chain reaction (PCR). It is
      shown that in colon tumours, the sensitivity of detecting a mutation is
      significantly higher when K-ras exon 1 is amplified prior to PCR with allele
      specific primers (mismatch PCR). It is shown that allele specific oligonucleotide
      probes which are non-radioactively labelled could be used to detect these point
      mutations. By utilizing this two-step PCR, K-ras codon 12 mutations were studied
      in 10 colon carcinoma cell lines and 25 colon tumours. By combining the two-step
      PCR together with non-radioactively labelled oligonucleotide probes, the
      detection of point mutations is both accurate and rapid.

PMID- 9778457
TI  - A reverse transcriptase polymerase chain reaction assay for the detection of
      thermophilic Campylobacter spp.
AB  - A novel method was developed for the detection of thermophilic enteropathogenic
      campylobacters based on the detection of mRNA using the reverse transcriptase
      polymerase chain reaction (RT-PCR). The RNA extraction method, DNase treatment
      and RT-PCR assay were shown to be specific for mRNA. The assay is specific for
      the thermophilic campylobacters Campylobacter jejuni, Campylobacter coli and
      Campylobacter upsaliensis and restriction fragment length polymorphism (RFLP)
      analysis of the 256 bp amplified product with the restriction endonucleases Alu
      I, Dde I and Dra I revealed distinct species specific patterns. The assay was
      applied to the detection of C. jejuni cells killed by heating at 72 degreesC for
      5 min and mRNA was detected by RT-PCR immediately after heat killing but became
      undetectable within 4 h when the cells were held at 37 degreesC. The assay
      therefore can differentiate between viable and dead cells of C. jejuni.

PMID- 9778458
TI  - Specific detection of the genus Serpulina, S. hyodysenteriae and S. pilosicoliin
      porcine intestines by fluorescent rRNA in situ hybridization.
AB  - A fluorescent-labelledin situ hybridization method targeting rRNA was devised to
      facilitate specific identification and diagnosis of diarrhoea and colitis in pigs
      caused by the genus Serpulina, as well as to distinguish the species Serpulina
      hyodysenteriae and Serpulina pilosicoli in formalin-fixed colon tissue sections.
      A genus-specific oligonucleotide probe SER1410 targeting the five species of
      porcine Serpulina was thus designed. Furthermore, species specific
      oligonucleotide probes (Hyo1210, Pilosi209 and Pilosi1405) were also designed to
      detect, identify and differentiate S. hyodysenteriae and S. pilosicoli. These
      probes clearly demonstrated and possessed the desired specificity, when evaluated
      by whole cell hybridization on five reference strains and 20 isolates covering
      the five species of porcine Serpulina. Furthermore, the oligonucleotide probes
      were specific when used both, for the detection of Serpulina isolates at genus
      level as well as for specific detection of S. hyodysenteriae and S. pilosicoli in
      formalin-fixed colon tissue sections from pigs suffering from swine dysentery and
      porcine colonic spirochaetosis, respectively. Tissue sections were also used from
      pigs without any intestinal disorders as controls for estimating the specificity
      of the probes. The probes developed in this study thus had the potential of
      specific identification and histological recognition obtained in the formalin
      fixed tissue samples.

PMID- 9778459
TI  - Detection of a high-frequency silent polymorphism (C-->T) in the kir2.1 (KCNJ2)
      inwardly rectifying potassium channel gene by polymerase chain reaction and
      single strand conformation polymorphism.
AB  - The aim of this work was to determine the frequency of a base substitution (C-
      >T) identified in the Kir2.1 gene (approved gene symbol: KCNJ2; OMIM number:
      600681). Polymerase chain reaction (PCR) of the area of the Kir2.1 gene
      containing this substitution was performed on 52 genomic DNA samples. Using
      single strand conformation polymorphism (SSCP) analysis, the genotype and allele
      frequencies were subsequently determined and the polymorphism identified in this
      study was verified by cycle sequencing. The data demonstrate that the C-->T
      nucleotide change identified corresponds to a silent polymorphism with a
      relatively high frequency. The deduced genotype frequencies of homozygotes and
      heterozygotes were: C/C: 73%; T/T: 2% and C/T: 25%. The deduced allele
      frequencies were C: 85.6% and T: 14.4%.

PMID- 9778460
TI  - Polymorphism at position 882 of the fibroblast growth factor receptor 3 (FGFR3)
      gene detected by SSCP analysis.

PMID- 9778461
TI  - Quantitation of glutaminase mRNA in enterocytes using competitive RT-PCR.
AB  - The concentration of mRNA within the intestinal mucosa is usually measured by
      either Northern blot analysis or semi-quantitative reverse transcription
      polymerase chain reaction (RT-PCR). However, these methods are limited by a lack
      of valid internal controls, low sensitivity, and large differences in the
      concentration of the internal control and target gene. The authors present an
      alternative method using competitive RT-PCR to measure glutaminase mRNA in
      isolated enterocytes.

PMID- 9778462
TI  - A PCR generated BsaJ I RFLP in the promoter of the von Hippel-Lindau disease
      (VHL) tumour suppressor gene.

PMID- 9778486
TI  - Cellular and molecular biology of vascular smooth muscle cells in pulmonary
      hypertension.

PMID- 9778487
TI  - Ion channels in the pulmonary vasculature.

PMID- 9778488
TI  - Short-term treatment with a low dose of inhaled fluticasone propionate decreases
      the number of CD1a+ dendritic cells in asthmatic airways.
AB  - The activation of T-lymphocytes through the recognition of specific allergens is
      a crucial event in the development of allergic inflammation. Dendritic cells (DC)
      are potent accessory cells that play an important role in initiating bronchial
      immune responses by activation of T-lymphocytes. We investigated the distribution
      of CD1a+ DC in the bronchial biopsies from asthmatic patients, and evaluated the
      effects of a short course of low dose inhaled fluticasone propionate treatment.
      Twenty-three mild to moderate stable asthmatic patients and eight normal subjects
      were included in the study. Bronchoscopy with bronchial biopsies were performed
      in each subject. Eighteen of the 23 asthmatics underwent a second bronchoscopy
      after 6 weeks of low dose inhaled fluticasone propionate treatment (250 mcg bd)
      in a placebo-controlled double-blind study. Biopsies were embedded into
      glycolmethacrylate resin and analysed by immunohistochemistry methods using
      specific monoclonal antibodies against CD1a, which is a widely recognized marker
      for DC. In asthmatics, CD1a+ DC number was significantly higher in bronchial
      epithelium (P < 0.001) and in lamina propria (P < 0.001) when compared with
      normal controls. In addition, we observed that a short course of low dose inhaled
      fluticasone propionate treatment decreased the number of CD1a+ DC in both the
      bronchial epithelium (P < 0.05) and lamina propria (P < 0.01). The increased
      number of CD1a+ DC support the hypothesis that DC play an important role in the
      modulation of the immune response in chronic asthma. Short-term low dose
      fluticasone propionate treatment induces down-regulation of the CD1a+ DC number.

PMID- 9778489
TI  - A tachykinin NK3 receptor antagonist, SR 142801 (osanetant), prevents substance P
      induced bronchial hyperreactivity in guinea-pigs.
AB  - Aerosolized substance P (0.1 M, for 30 min) induced airway hyperresponsiveness in
      guinea-pigs 24 h after they were pre-treated with salbutamol (8.7 mM by aerosol
      for 10 min) and phosphoramidon (0.1 mM by aerosol for 10 min). This was displayed
      by an exaggerated response to the bronchoconstrictor effect of acetylcholine. A
      microvascular leakage hypersensitivity also occurred and was demonstrated by a
      potentiation of the plasma protein extravasation from bronchial vessels induced
      by histamine. The aim of this study was to investigate the effects of the non
      peptide and potent tachykinin NK3 receptor antagonist, SR 142801 (osanetant), in
      comparison with those of the tachykinin NK1 and NK2 receptor antagonists, SR
      140333 (nolpitantium) and SR 48968 (saredutant) respectively, on substance P.
      When given once at 1 mg/kg i.p. 45 min before exposure to substance P, SR 142801
      prevented both hyperresponsiveness to acetylcholine and the potentiation of
      histamine-induced increase in microvascular permeability. SR 142801 did not
      exhibit any tachykinin NK1 or NK2 antagonistic activity in experiments on guinea
      pig isolated airways, in vitro or in vivo. The results suggest that tachykinin
      NK3 receptors might be involved in these substance P-induced effects on airways.

PMID- 9778490
TI  - The effect of tasuldine, a bronchosecretolytic agent, on mucus rheology and
      clearability and the interaction with acetylcholine in ferrets.
AB  - Tasuldine (Ts) is an orally active bronchosecretolytic agent shown to be
      clinically effective in human studies. Tasuldine decreases the sialomucin content
      of the mucus and, in animal studies, this modulation of the glycopeptide
      correlates with decreased mucus viscosity. The aim of this study was to evaluate
      the effect of tasuldine on mucus viscoelasticity and correlate the rheological
      changes to mucociliary and cough clearability. Tracheal mucus samples were
      collected from anaesthetized adult ferrets by a modification of the cytology
      brush technique. Mucus was collected prior to and following administration of
      either vehicle (normal saline) or Ts (10 mg/kg i.v.), and followed by
      acetylcholine (ACH) challenge (ca. 4 ml of 10(-2)M i.v., slow infusion). The
      analysis included magnetic microrheometry to measure the viscosity and elasticity
      of microlitre quantities of mucus. Mucociliary transportability (NFPTR) was
      measured by means of the frog palate assay and mucus collection rates (mg/min)
      were used as an indirect measure of secretion rate. The principal index of mucus
      rigidity, log G*, decreased with tasuldine infusion (P = 0.014) and further
      decreased with ACH (P = 0.002). In simple terms, the mucus became less rigid or
      more deformable with tasuldine administration, thus benefiting clearability based
      on predictions from model studies. The changes observed with acetylcholine alone
      were consistent with a classic secretagogue response--the outputting of a large
      volume of watery mucus. NFPTR increased with tasuldine treatment, and even
      further with acetylcholine; however, the combination of Ts and ACH resulted in a
      decrease in NFPTR close to baseline, which was likely due to the fact that the
      resulting mucus was too liquid for maximal mucociliary efficiency. The index of
      mucus flux (mg/min) was very much elevated with ACH compared with control; this
      was not the case with Ts. This indicates that tasuldine, despite improving the
      rheological properties of the mucus, did not stimulate hypersecretion, as was the
      case for acetylcholine. The changes in mucus rheology with infused tasuldine can
      be considered beneficial with respect to their effects on predicted mucociliary
      and cough clearability, supporting the clinical effectiveness of this type of
      mucolytic therapy in airway diseases such as chronic bronchitis. The study also
      illustrates the potential danger of overliquification of mucus.

PMID- 9778491
TI  - The potential roles of cytokines, IL-5 and IL-8, and plasma cortisol in the anti
      inflammatory actions of phosphodiesterase inhibitors in sensitized guinea-pig
      airways.
AB  - Ovalbumin (OvA) inhalation by sensitized guinea-pigs caused a pronounced rise in
      interleukin (IL)-5 in bronchoalveolar lavage (BAL) fluid at both 3 and 24 h after
      antigen exposure. The increased levels at 24 h were attenuated by the
      phosphodiesterase inhibitors Ro 20-1724 and aminophylline and by dexamethasone,
      all of which also attenuated the concurrent lung eosinophilia. The rise in IL-5
      at 3 h was additionally attenuated by the PDE3 inhibitor, siguazodan, which
      failed to attenuate the eosinophilia at 24 h. These results suggest a pivotal
      action of these compounds on the later rise in IL-5. Ro 20-1724, aminophylline,
      siguazodan and dexamethasone attenuated a rise in IL-8 levels in BAL fluid at 3 h
      and the subsequent neutrophilia at 24 h. There was no increase in plasma ACTH at
      3 and 24 h after OvA challenge but cortisol levels were elevated at 3 h. This was
      inhibited by Ro 20-1724, siguazodan and dexamethasone. Thus, elevation of plasma
      cortisol does not explain the anti-inflammatory actions of these compounds.
      Aminophylline, however, did raise plasma cortisol at both 3 and 24 h after
      antigen challenge which may be an important further mechanism of action for this
      compound.

PMID- 9778492
TI  - Effect of the mucoactive drug nacystelyn on the respiratory burst of human blood
      polymorphonuclear neutrophils.
AB  - In lung diseases such as chronic obstructive pulmonary disease (COPD) or cystic
      fibrosis, the activation of phagocytic cells produces high amounts of cytotoxic
      reactive oxygen species (ROS) that are partly implicated in the pathogenic
      process. In this study, the ex vivo antioxidant activity of nacystelyn (NAL), a
      recently developed mucoactive thiol-containing agent, was investigated using the
      respiratory burst of human blood polymorphonuclear neutrophils (PMNs). The ROS
      generation was induced by serum-opsonized zymosan and assessed with luminol- and
      lucigenin-enhanced chemiluminescence (ECL). The activity of NAL was compared with
      N-acetylcysteine (ACC) and captopril, other thiol-containing pharmacological
      agents having documented antioxidant properties. The three drugs significantly
      inhibited the ECL response of activated PMNs in the presence of luminol, a
      luminogenic agent which mostly reflects the production of hydroxyl and hypohalite
      radicals. NAL was more efficient than the other two drugs: the concentrations
      producing a 50% inhibition (IC50) of total luminol-ECL were 290 microM, 1580
      microM and 760 microM for NAL, ACC and captopril, respectively. The inhibition of
      the lucigenin-ECL response of activated PMNs was less marked for all compounds
      suggesting a poorer reactivity with superoxide radicals. These findings
      demonstrate that NAL, at concentrations obtainable in vivo by inhalation, impairs
      the PMNs chemiluminescence response related to hydroxyl and hypohalite radicals
      production. As those radicals are highly cytotoxic, NAL appears as a promising
      agent in the prevention of oxidative lung damage caused by an active inflammatory
      response.

PMID- 9778493
TI  - Characterisation of endothelin induced relaxation in guinea-pig airways: evidence
      for dilatory ETA- and ETB-receptors.
AB  - Receptors involved in endothelin induced relaxation were characterized on
      isolated circular segments of guinea-pig trachea. The motor responses to
      endothelin-1 (ET-1), ET-2 and ET-3 as well as the effects of the ETB-receptor
      agonist, BQ 3020, and the ETA-receptor antagonist, FR 139317, were tested. The
      responses obtained were analysed in relation to the nitric oxide (NO) synthase
      inhibition by NG-monomethyl L-arginine (L-NMMA). In submaximally precontracted
      tracheal segments ET-1 and ET-2 induced concentration-dependent dilatations. ET-3
      induced a biphasic response in precontracted segments, at low concentrations a
      small contraction followed by a dilatation at higher concentrations. FR 139317
      blocked the low concentration induced dilatation by ET-1/ET-2, unmasking a
      contractile response. The dilatation induced by higher ET-1/ET-2 concentrations
      was unaffected by FR 139317 which also did not affect the dilatory response of ET
      3. These results indicate the presence of two dilatory receptors. One of these
      was of ETA type, since it was antagonized by FR 139317 while the other receptor
      probably was of the ETB type, since all three endothelins in the moderate
      concentration range caused a uniform dilatation which was unaffected by FR
      139317. Furthermore, BQ 3020 induced potent relaxation of the precontracted
      segments. In resting tracheal segments all three endothelins caused an identical
      contraction, suggesting a contractile ETB-receptor. However, BQ 3020 along with
      another ETB-agonist, IRL 1620, failed to induce contraction which indicates the
      possibility of two different subtypes of the ETB-receptor, one involved in
      dilatation and the other in contraction. Experiments with the nitric oxide
      synthetase inhibitor L-NMMA on precontracted segments showed a similar change as
      when FR 139317 was used. This suggests that the dilatory ETA-receptor depends on
      nitric oxide (NO) for mediating the dilation. On the other hand, the dilatory ETB
      receptor response was unaffected by L-NMMA which suggests a mechanism unrelated
      to NO.

PMID- 9778494
TI  - Respiratory muscle overloading and dyspnoea during bronchoconstriction in asthma:
      protective effects of fenoterol.
AB  - Whether, and to what extent, beta 2-agonists protect against respiratory muscle
      overloading and breathlessness during bronchoconstriction remains to be defined
      in patients with asthma. In a double blind placebo-controlled study, 100
      micrograms of fenoterol were administered to six stable asthmatics before a
      bronchial provocation test, performed by inhaling doubling concentrations of
      histamine from a Devilbiss 646 nebulizer. We recorded breathing pattern (tidal
      volume VT, inspiratory time TI, total time of the respiratory cycle TTOT),
      inspiratory capacity (IC), dynamic pleural pressure swing (Pplsw), total lung
      resistance (RL) and FEV1. VT was expressed both in actual values and as % of IC.
      Changes in VT (%IC) during histamine inhalation reflected changes in dynamic end
      inspiratory lung volume (EILV). Pplsw was expressed as % of maximal (the most
      negative in sign) pleural pressure, obtained under control conditions during a
      sniff manoeuvre (Pplsn). Pplsw (%Pplsn) is an index of inspiratory muscle effort.
      The test ended when the concentration of histamine which caused a decrease in
      FEV1 of > or = 40% post-saline was reached. Dyspnoea rating was scored by a
      modified Borg scale. At the ultimate degree of bronchoconstriction (UDB) with
      histamine: (i) decrease in FEV1 was similar after placebo and fenoterol, while
      increase in RL was lower after fenoterol (P < 0.005); (ii) VT(%IC) increased less
      after fenoterol (P < 0.027); (iii) increases in Pplsw (%Pplsn) was lower after
      fenoterol (P < 0.001); (iv) delta Borg (from saline) was lower (P < 0.01) after
      fenoterol; (v) differences in delta Borg, from placebo to fenoterol, related to
      concurrent changes in VT(%IC) (r2 = 0.67). In conclusion, at UDB 100 micrograms
      of fenoterol produced a beneficial effect on the degree of inspiratory muscle
      loading and breathlessness, an effect greater than it would be expected from
      measuring FEV1 alone.

PMID- 9778495
TI  - Transducing positional information to the Hox genes: critical interaction of cdx
      gene products with position-sensitive regulatory elements.
AB  - Studies of pattern formation in the vertebrate central nervous system indicate
      that anteroposterior positional information is generated in the embryo by
      signalling gradients of an as yet unknown nature. We searched for transcription
      factors that transduce this information to the Hox genes. Based on the assumption
      that the activity levels of such factors might vary with position along the
      anteroposterior axis, we devised an in vivo assay to detect responsiveness of cis
      acting sequences to such differentially active factors. We used this assay to
      analyze a Hoxb8 regulatory element, and detected the most pronounced response in
      a short stretch of DNA containing a cluster of potential CDX binding sites. We
      show that differentially expressed DNA binding proteins are present in
      gastrulating embryos that bind to these sites in vitro, that cdx gene products
      are among these, and that binding site mutations that abolish binding of these
      proteins completely destroy the ability of the regulatory element to drive
      regionally restricted expression in the embryo. Finally, we show that ectopic
      expression of cdx gene products anteriorizes expression of reporter transgenes
      driven by this regulatory element, as well as that of the endogenous Hoxb8 gene,
      in a manner that is consistent with them being essential transducers of
      positional information. These data suggest that, in contrast to Drosophila
      Caudal, vertebrate cdx gene products transduce positional information directly to
      the Hox genes, acting through CDX binding sites in their enhancers. This may
      represent the ancestral mode of action of caudal homologues, which are involved
      in anteroposterior patterning in organisms with widely divergent body plans and
      modes of development.

PMID- 9778496
TI  - Neurofibromin modulation of ras activity is required for normal endocardial
      mesenchymal transformation in the developing heart.
AB  - Endocardial cushions are the precursors of the cardiac valves and form by a
      process of epithelial-mesenchymal transformation. Secreted growth factors from
      myocardium induce endocardial cells to transform into mesenchyme and invade the
      overlying extracellular matrix. Here, we show that the product of the Nf1
      neurofibromatosis gene is required to regulate this event. In the absence of
      neurofibromin, mouse embryo hearts develop overabundant endocardial cushions due
      to hyperproliferation and lack of normal apoptosis. Neurofibromin deficiency in
      explant cultures is reproduced by activation of ras signaling pathways, and the
      Nf1(-/-) mutant phenotype is prevented by inhibiting ras in vitro. These results
      indicate that neurofibromin normally acts to modulate epithelial-mesenchymal
      transformation and proliferation in the developing heart by down regulating ras
      activity.

PMID- 9778497
TI  - not really finished is crucial for development of the zebrafish outer retina and
      encodes a transcription factor highly homologous to human Nuclear Respiratory
      Factor-1 and avian Initiation Binding Repressor.
AB  - Not really finished (nrf), a larval-lethal mutation in zebrafish generated by
      retroviral insertion, causes specific retinal defects. Analysis of mutant retinae
      reveals an extensive loss of photoreceptors and their precursors around the onset
      of visual function. These neurons undergo apoptosis during differentiation,
      affecting all classes of photoreceptors, suggesting an essential function of nrf
      for the development of all types of photoreceptors. In the mutant, some
      photoreceptors escape cell death, are functional and, as judged by opsin
      expression, belong to at least three classes of cones and one class of rods. The
      protein encoded by nrf is a close homologue of human Nuclear Respiratory Factor 1
      and avian Initiation Binding Repressor, transcriptional regulators binding the
      upstream consensus sequence RCGCRYGCGY. At 24 hours of development, prior to
      neuronal differentiation, nrf is expressed ubiquitously throughout the developing
      retina and central nervous system. At 48 hours of development, expression of nrf
      is detected in the ganglion cell layer, in the neurons of the inner nuclear
      layer, and in the optic nerve and optic tracts, and, at 72 hours of development,
      is no longer detectable by in situ hybridization. Mutants contain no detectable
      nrf mRNA and die within 2 weeks postfertilization as larvae with reduced brain
      size. On the basis of its similarity with NRF-1 and IBR, nrf is likely involved
      in transcriptional regulation of multiple target genes, including those that
      encode mitochondrial proteins, growth factor receptors and other transcription
      factors. This demonstrates the power of insertional mutagenesis as a means for
      characterizing novel genes necessary for vertebrate retinal development.

PMID- 9778498
TI  - Heartbroken is a specific downstream mediator of FGF receptor signalling in
      Drosophila.
AB  - Drosophila possesses two FGF receptors which are encoded by the heartless and
      breathless genes. HEARTLESS is essential for early migration and patterning of
      the embryonic mesoderm, while BREATHLESS is required for proper branching of the
      tracheal system. We have identified a new gene, heartbroken, that participates in
      the signalling pathways of both FGF receptors. Mutations in heartbroken are
      associated with defects in the migration and later specification of mesodermal
      and tracheal cells. Genetic interaction and epistasis experiments indicate that
      heartbroken acts downstream of the two FGF receptors but either upstream of or
      parallel to RAS1. Furthermore, heartbroken is involved in both the HEARTLESS- and
      BREATHLESS-dependent activation of MAPK. In contrast, EGF receptor-dependent
      embryonic functions and MAPK activation are not perturbed in heartbroken mutant
      embryos. A strong heartbroken allele also suppresses the effects of
      hyperactivated FGF but not EGF receptors. Thus, heartbroken may contribute to the
      specificity of developmental responses elicited by FGF receptor signalling.

PMID- 9778499
TI  - A highly conserved centrosomal kinase, AIR-1, is required for accurate cell cycle
      progression and segregation of developmental factors in Caenorhabditis elegans
      embryos.
AB  - S. cerevisiae Ipl1, Drosophila Aurora, and the mammalian centrosomal protein IAK
      1 define a new subfamily of serine/threonine kinases that regulate chromosome
      segregation and mitotic spindle dynamics. Mutations in ipl1 and aurora result in
      the generation of severely aneuploid cells and, in the case of aurora, monopolar
      spindles arising from a failure in centrosome separation. Here we show that a
      related, essential protein from C. elegans, AIR-1 (Aurora/Ipl1 related), is
      localized to mitotic centrosomes. Disruption of AIR-1 protein expression in C.
      elegans embryos results in severe aneuploidy and embryonic lethality. Unlike
      aurora mutants, this aneuploidy does not arise from a failure in centrosome
      separation. Bipolar spindles are formed in the absence of AIR-1, but they appear
      to be disorganized and are nucleated by abnormal-looking centrosomes. In addition
      to its requirement during mitosis, AIR-1 may regulate microtubule-based
      developmental processes as well. Our data suggests AIR-1 plays a role in P
      granule segregation and the association of the germline factor PIE-1 with
      centrosomes.

PMID- 9778500
TI  - Determination of the zebrafish forebrain: induction and patterning.
AB  - We report an analysis of forebrain determination and patterning in the zebrafish
      Danio rerio. In order to study these events, we isolated zebrafish homologs of
      two neural markers, odd-paired-like (opl), which encodes a zinc finger protein,
      and fkh5, which encodes a forkhead domain protein. At mid-gastrula, expression of
      these genes defines a very early pattern in the presumptive neurectoderm, with
      opl later expressed in the telencephalon, and fkh5 in the diencephalon and more
      posterior neurectoderm. Using in vitro explant assays, we show that forebrain
      induction has occurred even earlier, by the onset of gastrulation (shield stage).
      Signaling from the early gastrula shield, previously shown to be an organizing
      center, is sufficient for activation of opl expression in vitro. In order to
      determine whether the organizer is required for opl regulation, we removed from
      late blastula stage embryos either the presumptive prechordal plate, marked by
      goosecoid (gsc) expression, or the entire organizer, marked by chordin (chd)
      expression. opl was correctly expressed after removal of the presumptive
      prechordal plate and consistently, opl was correctly expressed in one-eyed
      pinhead (oep) mutant embryos, where the prechordal plate fails to form. However,
      after removal of the entire organizer, no opl expression was observed, indicating
      that this region is crucial for forebrain induction. We further show that
      continued organizer function is required for forebrain induction, since beads of
      BMP4, which promotes ventral fates, also prevented opl expression when implanted
      during gastrulation. Our data show that forebrain specification begins early
      during gastrulation, and that a wide area of dorsal mesendoderm is required for
      its patterning.

PMID- 9778501
TI  - The role of Alx-4 in the establishment of anteroposterior polarity during
      vertebrate limb development.
AB  - We have determined that Strong's Luxoid (lstJ) [corrected] mice have a 16 bp
      deletion in the homeobox region of the Alx-4 gene. This deletion, which leads to
      a frame shift and a truncation of the Alx-4 protein, could cause the polydactyly
      phenotype observed in lstJ [corrected] mice. We have cloned the chick homologue
      of Alx-4 and investigated its expression during limb outgrowth. Chick Alx-4
      displays an expression pattern complementary to that of shh, a mediator of
      polarizing activity in the limb bud. Local application of Sonic hedgehog (Shh)
      and Fibroblast Growth Factor (FGF), in addition to ectodermal apical ridge
      removal experiments suggest the existence of a negative feedback loop between Alx
      4 and Shh during limb outgrowth. Analysis of polydactylous mutants indicate that
      the interaction between Alx-4 and Shh is independent of Gli3, a negative
      regulator of Shh in the limb. Our data suggest the existence of a negative
      feedback loop between Alx-4 and Shh during vertebrate limb outgrowth.

PMID- 9778502
TI  - Downregulation of atrial markers during cardiac chamber morphogenesis is
      irreversible in murine embryos.
AB  - Vertebrate cardiogenesis is a complex process involving multiple, distinct tissue
      types which interact to form a four-chambered heart. Molecules have been
      identified whose expression patterns co-segregate with the maturation of the
      atrial and ventricular muscle cell lineages. It is not currently known what role
      intrinsic events versus external influences play in cardiac chamber
      morphogenesis. We developed novel, fluorescent-based, myocardial, cellular
      transplantation systems in order to study these questions in murine embryos and
      report the irreversible nature of chamber specification with respect to the
      downregulation of atrial myosin light chain 2 (MLC-2a) and alpha myosin heavy
      chain (alpha-MHC). Grafting ventricular cells into the atrial chamber does not
      result in upregulation of MLC-2a expression in ventricular cells. Additionally,
      wild-type ventricular muscle cells grafted into the wild-type background
      appropriately downregulate MLC-2a and alpha-MHC. Finally, grafting of RXRalpha
      gene-deficient ventricular muscle cells into the ventricular chambers of wild
      type embryos does not rescue the persistent expression of MLC-2a, providing
      further evidence that ventricular chamber maturation is an early event. These
      studies provide a new approach for the mechanistic dissection of critical
      signaling events during cardiac chamber growth, maturation and morphogenesis in
      the mouse, and should find utility with other approaches of cellular
      transplantation in murine embryos. These experiments document the irreversible
      nature of the downregulation of atrial markers after the onset of cardiogenesis
      during ventricular chamber morphogenesis and temporally define the response of
      cardiac muscle cells to signals regulating chamber specification.

PMID- 9778503
TI  - Vertebrate tinman homologues XNkx2-3 and XNkx2-5 are required for heart formation
      in a functionally redundant manner.
AB  - Tinman is a Drosophila homeodomain protein that is required for formation of both
      visceral and cardiac mesoderm, including formation of the dorsal vessel, a heart
      like organ. Although several vertebrate tinman homologues have been
      characterized, their requirement in earliest stages of heart formation has been
      an open question, perhaps complicated by potential functional redundancy of
      tinman homologues. We have utilized a novel approach to investigate functional
      redundancy within a gene family, by coinjecting DNA encoding dominantly acting
      repressor derivatives specific for each family member into developing Xenopus
      embryos. Our results provide the first evidence that vertebrate tinman homologues
      are required for earliest stages of heart formation, and that they are required
      in a functionally redundant manner. Coinjection of dominant repressor constructs
      for both XNkx2-3 and XNkx2-5 is synergistic, resulting in a much higher frequency
      of mutant phenotypes than that obtained with injection of either dominant
      repressor construct alone. Rescue of mutant phenotypes can be effected by
      coinjection of either wild-type tinman homologue. The most extreme mutant
      phenotype is a complete absence of expression of XNkx2-5 in cardiogenic mesoderm,
      an absence of markers of differentiated myocardium, and absence of
      morphologically distinguishable heart on the EnNkxHD-injected side of the embryo.
      This phenotype represents the most severe cardiac phenotype of any vertebrate
      mutant yet described, and underscores the importance of the tinman family for
      heart development. These results provide the first in vivo evidence that XNkx2-3
      and XNkx2-5 are required as transcriptional activators for the earliest stages of
      heart formation. Furthermore, our results suggest an intriguing mechanism by
      which functional redundancy operates within a gene family during development. Our
      experiments have been performed utilizing a recently developed transgenic
      strategy, and attest to the efficacy of this strategy for enabling transgene
      expression in limited cell populations within the developing Xenopus embryo.

PMID- 9778504
TI  - Sperm-triggered calcium oscillations during meiosis in ascidian oocytes first
      pause, restart, then stop: correlations with cell cycle kinase activity.
AB  - We have investigated the relationship between the sperm-triggered Ca2+
      oscillations and the activities of two cell cycle kinases (MPF activity and MAP
      kinase activity) at fertilisation of Ascidiella aspersa oocytes. Maturation
      Promoting Factor (MPF) activity is elevated in the metaphase I (MI)-arrested
      unfertilised oocyte (as measured by phosphorylation of exogenous histone H1) and
      falls 5 minutes after fertilisation to remain at low levels for 5 minutes. The
      first polar body (pb1) is extruded when the MPF activity is low. The MPF activity
      is elevated again 15 minutes after fertilisation and finally becomes inactivated
      25 minutes after fertilisation when the pb2 is extruded. MAP kinase activity
      increases from an initially elevated level to reach maximal activity 10 minutes
      after fertilisation and subsequently falls to reach low levels 25 minutes after
      fertilisation. Sperm trigger a series of Ca2+ oscillations that pause for 5
      minutes while only the MPF activity is low and are present when both MPF and MAP
      kinase activity are elevated. We next attempted to determine whether the second
      phase of calcium oscillations is required to reactivate the MPF activity that
      precedes extrusion of the second polar body. To do this, we triggered a monotonic
      Ca2+ signal. This leads to the inactivation of MPF followed by MPF reactivation.
      The MPF activity then remains elevated for an extended period of time. During
      this period, the chromatin remains condensed and a metaphase II (MII) spindle
      forms. Fertilisation of these MII oocytes triggers extrusion of pb2 in 7 minutes.
      Interestingly, the second phase of Ca2+ oscillations is completely absent when
      MII oocytes are fertilised. Thus, in both MI and MII oocytes, the sperm-triggered
      Ca2+ oscillations follow the MPF activity. Finally we discuss our finding that
      the Ca2+ release system remains sensitive during the metaphase-like state
      (including the period when the Ca2+ oscillations pause).

PMID- 9778505
TI  - A GATA-dependent nkx-2.5 regulatory element activates early cardiac gene
      expression in transgenic mice.
AB  - nkx-2.5 is one of the first genes expressed in the developing heart of early
      stage vertebrate embryos. Cardiac expression of nkx-2.5 is maintained throughout
      development and nkx-2.5 also is expressed in the developing pharyngeal arches,
      spleen, thyroid and tongue. Genomic sequences flanking the mouse nkx-2.5 gene
      were analyzed for early developmental regulatory activity in transgenic mice.
      Approximately 3 kb of 5' flanking sequence is sufficient to activate gene
      expression in the cardiac crescent as early as E7.25 and in limited regions of
      the developing heart at later stages. Expression also was detected in the
      developing spleen anlage at least 24 hours before the earliest reported spleen
      marker and in the pharyngeal pouches and their derivatives including the thyroid.
      The observed expression pattern from the -3 kb construct represents a subset of
      the endogenous nkx-2.5 expression pattern which is evidence for compartment
      specific nkx-2.5 regulatory modules. A 505 bp regulatory element was identified
      that contains multiple GATA, NKE, bHLH, HMG and HOX consensus binding sites. This
      element is sufficient for gene activation in the cardiac crescent and in the
      heart outflow tract, pharynx and spleen when linked directly to lacZ or when
      positioned adjacent to the hsp68 promoter. Mutation of paired GATA sites within
      this element eliminates gene activation in the heart, pharynx and spleen
      primordia of transgenic embryos. The dependence of this nkx-2. 5 regulatory
      element on GATA sites for gene activity is evidence for a GATA-dependent
      regulatory mechanism controlling nkx-2.5 gene expression. The presence of
      consensus binding sites for other developmentally important regulatory factors
      within the 505 bp distal element suggests that combinatorial interactions between
      multiple regulatory factors are responsible for the initial activation of nkx-2.5
      in the cardiac, thyroid and spleen primordia.

PMID- 9778506
TI  - Eve and ftz regulate a wide array of genes in blastoderm embryos: the selector
      homeoproteins directly or indirectly regulate most genes in Drosophila.
AB  - The selector homeoproteins are a highly conserved group of transcription factors
      found throughout the Eumetazoa. Previously, the Drosophila selector homeoproteins
      Eve and Ftz were shown to bind with similar specificities to all genes tested,
      including four genes chosen because they were thought to be unlikely targets of
      Eve and Ftz. Here, we demonstrate that the expression of these four unexpected
      targets is controlled by Eve and probably by the other selector homeoproteins as
      well. A correlation is observed between the level of DNA binding and the degree
      to which gene expression is regulated by Eve. Suspecting that the selector
      homeoproteins may affect many more genes than previously thought, we have
      characterized the expression of randomly selected genes at different stages of
      embryogenesis. At cellular blastoderm, 25-50% of genes whose transcription can be
      monitored are regulated by both Eve and Ftz. In late embryogenesis, 87% of genes
      are directly or indirectly controlled by most or all selector homeoproteins. We
      argue that this broad control of gene expression is essential to coordinate
      morphogenesis. Our results raise the possibility that each selector homeoprotein
      may directly regulate the expression of most genes.

PMID- 9778507
TI  - The roles of the homeobox genes aristaless and Distal-less in patterning the legs
      and wings of Drosophila.
AB  - In the leg and wing imaginal discs of Drosophila, the expression domains of the
      homeobox genes aristaless (al) and Distal-less (Dll) are defined by the secreted
      signaling molecules Wingless (Wg) and Decapentaplegic (Dpp). Here, the roles
      played by al and Dll in patterning the legs and wings have been investigated
      through loss of function studies. In the developing leg, al is expressed at the
      presumptive tip and a molecularly defined null allele of al reveals that its only
      function in patterning the leg appears to be to direct the growth and
      differentiation of the structures at the tip. In contrast, Dll has previously
      been shown to be required for the development of all of the leg more distal than
      the coxa. Dll protein can be detected in a central domain in leg discs throughout
      most of larval development, and in mature discs this domain corresponds to the
      distal-most region of the leg, the tarsus and the distal tibia. Clonal analysis
      reveals that late in development these are the only regions in which Dll function
      is required. However, earlier in development Dll is required in more proximal
      regions of the leg suggesting it is expressed at high levels in these cells early
      in development but not later. This reveals a correlation between a temporal
      requirement for Dll and position along the proximodistal axis; how this may
      relate to the generation of the P/D axis is discussed. Dll is required in the
      distal regions of the leg for the expression of tarsal-specific genes including
      al and bric-a-brac. Dll mutant cells in the leg sort out from wild-type cells
      suggesting one function of Dll here is to control adhesive properties of cells.
      Dll is also required for the normal development of the wing, primarily for the
      differentiation of the wing margin.

PMID- 9778509
TI  - Vascularization in the murine allantois occurs by vasculogenesis without
      accompanying erythropoiesis.
AB  - The aim of this study was to determine whether the blood vessels of the murine
      allantois are formed by vasculogenesis or angiogenesis. Morphological analysis
      revealed that differentiation of allantoic mesoderm into an outer layer of
      mesothelium and an inner vascular network begins in the distal region of the
      allantois, which is most remote from other tissues, as early as the late neural
      plate stage (approximately 7.75 days postcoitum). Nascent blood vessels were not
      found in the base of the allantois until 4-somite pairs had formed in the fetus
      (approximately 8.25 days postcoitum), and vascular continuity with the yolk sac
      and fetus was not present until the 6-somite-pair stage (approximately 8.5 days
      postcoitum). Immunohistochemical analysis demonstrated that flk-1, a molecular
      marker of early endothelial cells, is expressed in significantly more distal than
      basal core cells in the early allantois and never in mesothelium. Furthermore,
      synchronous grafting of donor yolk sac containing blood islands into blood
      islands of headfold-stage host conceptuses provided no evidence that the yolk sac
      contributes endothelial cells to the allantois. Finally, when removed from
      conceptuses and cultured in isolation, neural plate and headfold-stage
      allantoises formed a conspicuous vascular network that was positive for Flk-1.
      Hence, the vasculature of the allantois is formed intrinsically by vasculogenesis
      rather than extrinsically via angiogenesis from the adjacent yolk sac or fetus.
      Whether allantoic vasculogenesis is associated with erythropoiesis was also
      investigated. Benzidine-staining in situ revealed that primitive erythroid cells
      were not identified in the allantois until 6-somite pairs when continuity between
      its vasculature and that of the yolk sac was first evident. Nevertheless, a small
      number of allantoises removed from conceptuses at a considerably earlier stage
      were found to contain erythroid precursor cells following culture in isolation.
      To determine whether such erythroid cells could be of allantoic origin, host
      allantoises were made chimeric with lacZ-expressing donor allantoises that were
      additionally labeled with [3H]methyl thymidine. Following culture and
      autoradiography, many lacZ-expressing benzidine-stained cells were observed in
      donor allantoises, but none contained silver grains above background. Moreover,
      no cells of donor allantoic origin were found in the fetus or yolk sac. Hence,
      vasculogenesis seems to be independent of erythropoiesis in the allantois and to
      involve a distal-to-proximal gradient in differentiation of allantoic mesoderm
      into the endothelial cell lineage. Furthermore, this gradient is established
      earlier than reported previously, being present at the neural plate stage.

PMID- 9778508
TI  - The Polycomb-group gene eed is required for normal morphogenetic movements during
      gastrulation in the mouse embryo.
AB  - We have characterized an induced mutation, called embryonic ectoderm development
      or eed, that disrupts A-P patterning of the mouse embryo during gastrulation.
      Positional cloning of this gene revealed it to be the highly conserved homologue
      of the Drosophila gene extra sex combs, which is required for maintenance of long
      term transcriptional repression of homeotic gene expression. Mouse embryos
      homozygous for loss-of-function alleles of eed initiate gastrulation but display
      abnormal mesoderm production. Very little embryonic mesoderm is produced; in
      contrast, extraembryonic mesoderm is relatively abundant. These observations,
      along with mRNA in situ hybridization analyses, suggested a defect in the
      anterior primitive streak, from which much of the embryonic mesoderm of the wild
      type embryo is derived. To analyse this defect, we initiated clonal analysis of
      the pre-streak epiblast in eed mutant embryos, using the lineage tracer
      horseradish peroxidase (HRP). The results of these studies indicate that epiblast
      cells ingress through the anterior streak, but the newly formed mesoderm does not
      migrate anteriorly and is mislocalized to the extraembryonic compartment.
      Abnormal localization of mesoderm to the extraembryonic region did not appear to
      be due to a restriction and alteration of distal epiblast cell fate, since the
      majority of clones produced from regions fated to ingress through the anterior
      streak were mixed, displaying descendants in both embryonic and extraembryonic
      derivatives. eed mutant embryos also fail to display proper epiblast expansion,
      particularly with respect to the A-P axis. Based on patterns of clonal spread and
      calculated clone doubling times for the epiblast, this does not appear to be due
      to decreased epiblast growth. Rather, epiblast, which is normally fated to make a
      substantial contribution to the axial midline, appears to make mesoderm
      preferentially. The data are discussed in terms of global morphogenetic movements
      in the mouse gastrula and a disruption of signalling activity in the anterior
      primitive streak.

PMID- 9778510
TI  - Drosophila engrailed can substitute for mouse Engrailed1 function in mid
      hindbrain, but not limb development.
AB  - The Engrailed-1 gene, En1, a murine homologue of the Drosophila homeobox gene
      engrailed (en), is required for midbrain and cerebellum development and
      dorsal/ventral patterning of the limbs. In Drosophila, en is involved in
      regulating a number of key patterning processes including segmentation of the
      epidermis. An important question is whether, during evolution, the biochemical
      properties of En proteins have been conserved, revealing a common underlying
      molecular mechanism to their diverse developmental activities. To address this
      question, we have replaced the coding sequences of En1 with Drosophila en. Mice
      expressing Drosophila en in place of En1 have a near complete rescue of the
      lethal En1 mutant brain defect and most skeletal abnormalities. In contrast,
      expression of Drosophila en in the embryonic limbs of En1 mutants does not lead
      to repression of Wnt7a in the embryonic ventral ectoderm or full rescue of the
      embryonic dorsal/ventral patterning defects. Furthermore, neither En2 nor en
      rescue the postnatal limb abnormalities that develop in rare En1 null mutants
      that survive. These studies demonstrate that the biochemical activity utilized in
      mouse to mediate brain development has been retained by Engrailed proteins across
      the phyla, and indicate that during evolution vertebrate En proteins have
      acquired two unique functions during embryonic and postnatal limb development and
      that only En1 can function postnatally.

PMID- 9778511
TI  - Cis-interactions between Delta and Notch modulate neurogenic signalling in
      Drosophila.
AB  - We find that ectopic expression of Delta or Serrate in neurons within developing
      bristle organs is capable of non-autonomously inducing the transformation of the
      pre-trichogen cell into a tormogen cell in a wide variety of developmental
      contexts. The frequencies at which Delta can induce these transformations are
      dependent on the level of ectopic Delta expression and the levels of endogenous
      Notch signalling pathway components. The pre-trichogen cell becomes more
      responsive to Delta- or Serrate-mediated transformation when the level of
      endogenous Delta is reduced and less responsive when the dosage of endogenous
      Delta is increased, supporting the hypothesis that Delta interferes autonomously
      with the ability of a cell to receive either signal. We also find that a dominant
      negative form of Notch, ECN, is capable of autonomously interfering with the
      ability of a cell to generate the Delta signal. When the region of Notch that
      mediates trans-interactions between Delta and the Notch extracellular domain is
      removed from ECN, the ability of Delta to signal is restored. Our findings imply
      that cell-autonomous interactions between Delta and Notch can affect the ability
      of a cell to generate and to transduce a Delta-mediated signal. Finally, we
      present evidence that the Fringe protein can interfere with Delta- and Serrate
      mediated signalling within developing bristle organs, in contrast to previous
      reports of the converse effects of Fringe on Delta signalling in the developing
      wing.

PMID- 9778512
TI  - Homologous association of the Bithorax-Complex during embryogenesis: consequences
      for transvection in Drosophila melanogaster.
AB  - Transvection is the phenomenon by which the expression of a gene can be
      controlled by its homologous counterpart in trans, presumably due to pairing of
      alleles in diploid interphase cells. Transvection or trans-sensing phenomena have
      been reported for several loci in Drosophila, the most thoroughly studied of
      which is the Bithorax-Complex (BX-C). It is not known how early trans-sensing
      occurs nor the extent or duration of the underlying physical interactions. We
      have investigated the physical proximity of homologous genes of the BX-C during
      Drosophila melanogaster embryogenesis by applying fluorescent in situ
      hybridization techniques together with high-resolution confocal light microscopy
      and digital image processing. The association of homologous alleles of the BX-C
      starts in nuclear division cycle 13, reaches a plateau of 70% in postgastrulating
      embryos, and is not perturbed by the transcriptional state of the genes
      throughout embryogenesis. Pairing frequencies never reach 100%, indicating that
      the homologous associations are in equilibrium with a dissociated state. We
      determined the effects of translocations and a zeste protein null mutation, both
      of which strongly diminish transvection phenotypes, on the extent of diploid
      homologue pairing. Although translocating one allele of the BX-C from the right
      arm of chromosome 3 to the left arm of chromosome 3 or to the X chromosome
      abolished trans-regulation of the Ultrabithorax gene, pairing of homologous
      alleles surprisingly was reduced only to 20-30%. A zeste protein null mutation
      neither delayed the onset of pairing nor led to unpairing of the homologous
      alleles. These data are discussed in the light of different models for trans
      regulation. We examined the onset of pairing of the chromosome 4 as well as of
      loci near the centromere of chromosome 3 and near the telomere of 3R in order to
      test models for the mechanism of homologue pairing.

PMID- 9778513
TI  - A cap 'n' collar protein isoform contains a selective Hox repressor function.
AB  - We have characterized a protein isoform (CncB) from the Drosophila cap 'n' collar
      locus that selectively represses cis-regulatory elements that are activated by
      the Hox protein Deformed. Of the three Cnc protein isoforms, CncB is expressed in
      a localized pattern in mandibular and labral cells of the head during mid-stages
      of embryogenesis. When CncB protein is absent or reduced, mandibular cells are
      homeotically transformed toward maxillary identities. This transformation is
      associated with persistent Deformed expression in anterior mandibular cells,
      since the Deformed autoactivation circuit is normally antagonized by CncB
      function in these cells. Heat-shock-induced ectopic expression of CncB in mid
      stages of embryogenesis is sufficient to attenuate the activity of Dfd response
      elements in maxillary epidermal cells, but appears to have no effect in trunk
      epidermal cells on either the function or the response elements of other Hox
      proteins. CncB provides a mechanism to modulate the specificity of Hox
      morphogenetic outcomes, which results in an increase in the segmental diversity
      in the Drosophila head.

PMID- 9778514
TI  - Requirement of the MADS-box transcription factor MEF2C for vascular development.
AB  - The embryonic vasculature develops from endothelial cells that form a primitive
      vascular plexus which recruits smooth muscle cells to form the arterial and
      venous systems. The MADS-box transcription factor MEF2C is expressed in
      developing endothelial cells and smooth muscle cells (SMCs), as well as in
      surrounding mesenchyme, during embryogenesis. Targeted deletion of the mouse
      MEF2C gene resulted in severe vascular abnormalities and lethality in homozygous
      mutants by embryonic day 9.5. Endothelial cells were present and were able to
      differentiate, but failed to organize normally into a vascular plexus, and smooth
      muscle cells did not differentiate in MEF2C mutant embryos. These vascular
      defects resemble those in mice lacking the vascular-specific endothelial cell
      growth factor VEGF or its receptor Flt-1, both of which are expressed in MEF2C
      mutant embryos. These results reveal multiple roles for MEF2C in vascular
      development and suggest that MEF2-dependent target genes mediate endothelial cell
      organization and SMC differentiation.

PMID- 9778515
TI  - Intraaortic hemopoietic cells are derived from endothelial cells during ontogeny.
AB  - We have investigated the developmental relationship of the hemopoietic and
      endothelial lineages in the floor of the chicken aorta, a site of hemopoietic
      progenitor emergence in the embryo proper. We show that, prior to the onset of
      hemopoiesis, the aortic endothelium uniformly expresses the endothelium-specific
      membrane receptor VEGF-R2. The onset of hemopoiesis can be determined by
      detecting the common leukocyte antigen CD45. VEGF-R2 and CD45 are expressed in
      complementary fashion, namely the hemopoietic cluster-bearing floor of the aorta
      is CD45(+)/VEGF-R2(-), while the rest of the aortic endothelium is CD45(-)/VEGF
      R2(+). To determine if the hemopoietic clusters are derived from endothelial
      cells, we tagged the E2 endothelial tree from the inside with low-density
      lipoproteins (LDL) coupled to DiI. 24 hours later, hemopoietic clusters were
      labelled by LDL. Since no CD45(+) cells were inserted among endothelial cells at
      the time of vascular labelling, hemopoietic clusters must be concluded to derive
      from precursors with an endothelial phenotype.

PMID- 9778516
TI  - Stage-specific expression of the Kit receptor and its ligand (KL) during male
      gametogenesis in the mouse: a Kit-KL interaction critical for meiosis.
AB  - The Kit receptor and its ligand KL, which together constitute an essential
      effector at various stages of embryonic development, are both present during
      adult gametogenesis. In the testis, KL is expressed in Sertoli cells, and Kit in
      germ cells, starting at the premeiotic stages. A series of observations indicated
      previously a role in spermatogonia survival, without excluding a possible
      function at later stages. We identified a complex pattern of expression of the
      two components in the adult murine testis, suggestive of a role in the meiotic
      progression of spermatocytes. At stages VII-VIII of the cycle of the seminiferous
      epithelium, the time when spermatocytes enter meiosis, the membrane-associated
      form of KL extends on the Sertoli cell from the peripheral to the adluminal
      compartment of the tubule. We also found that the receptor is present on the
      surface of germ cells up to the pachytene stage. The availability of
      differentiated Sertoli cell lines, which express the KL protein and support part
      of the maturation of germ cells in coculture, allowed us to ask whether, in the
      in vitro reconstructed system, transit of spermatocytes through meiosis requires
      the Kit-KL interaction. Addition of a blocking monoclonal antibody against the
      Kit receptor (ACK2) inhibited extensively the appearance of haploid cells and the
      expression of a haploid-phase-specific gene (Prm1). Recognition of the supporting
      Sertoli cell by germ cells was not affected, indicating a requirement for the
      activity of the receptor for either entering or completing meiosis. Involvement
      of the membrane-associated form of the ligand was suggested by the observation
      that addition of the soluble form of KL was equally inhibitory.

PMID- 9778517
TI  - Receptor tyrosine phosphatases: the worm clears the picture.
AB  - Recent work on the Caenorhabditis elegans clr-1 gene shows that the receptor
      tyrosine phosphatase that it encodes negatively regulates a receptor tyrosine
      kinase related to mammalian fibroblast growth factor receptors. This opens up a
      promising system for investigating receptor tyrosine phosphatase function.

PMID- 9778518
TI  - Protein targeting: getting into the groove.
AB  - The 54 kDa subunit of the signal recognition particle has to identify a diverse
      family of substrates and deliver them in a controlled manner to the translocation
      machinery of the endoplasmic reticulum. Important new insights into the function
      of this sorting protein have emerged from recent biochemical and structural
      studies.

PMID- 9778519
TI  - Conservation biology: genes are not enough.
AB  - A study of correlated genotypic and phenotypic changes over a 2400-year period in
      a cave population of pocket gophers bolsters the idea that small, isolated
      populations can not only persist in a fluctuating environment, but may be able to
      adapt without genetic input from elsewhere.

PMID- 9778520
TI  - Hematopoiesis: progenitors and their genetic program.
AB  - Recent advances in our understanding of blood cell development have included the
      identification of a hematopoietic progenitor derived from endothelial cells and
      the possibility that the embryonic and fetal environment can reprogram gene
      expression in adult hematopoietic stem cells.

PMID- 9778521
TI  - Parasite immunology: pathways for expelling intestinal helminths.
AB  - Helminth parasites induce strong immune responses that are initiated by
      cytokines, in the first instance interleukin-4 and interleukin-13. Recent studies
      of knockout mice deficient in these mediators or their shared receptor have
      revealed discrete pathways required for expulsion of different gut parasites.

PMID- 9778523
TI  - Neuronal diversity: too many cell types for comfort?
AB  - Recent studies indicate that there are many more different types of neuron in the
      brain than previously thought. This richness will complicate life for those
      aiming to understand how the brain works - particularly for the neural modellers.

PMID- 9778522
TI  - Receptor clustering: activate to accumulate?
AB  - Postsynaptic receptor clustering is thought to be of critical importance in
      central neurotransmission. Recent work suggests that the formation and size of
      such clusters may depend on synaptic activity, although that dependence appears
      to vary according to the type of receptor that mediates the postsynaptic
      response.

PMID- 9778524
TI  - Sensory bases of navigation.
AB  - Navigating animals need to know both the bearing of their goal (the 'map' step),
      and how to determine that direction (the 'compass' step). Compasses are typically
      arranged in hierarchies, with magnetic backup as a last resort when celestial
      information is unavailable. Magnetic information is often essential to
      calibrating celestial cues, though, and repeated recalibration between celestial
      and magnetic compasses is important in many species. Most magnetic compasses are
      based on magnetite crystals, but others make use of induction or paramagnetic
      interactions between short-wavelength light and visual pigments. Though odors may
      be used in some cases, most if not all long-range maps probably depend on
      magnetite. Magnetitebased map senses are used to measure only latitude in some
      species, but provide the distance and direction of the goal in others.

PMID- 9778525
TI  - Chromosome arrangement within a bacterium.
AB  - BACKGROUND: The contour length of the circular chromosome of bacteria is greater
      than a millimeter but must be accommodated within a cell that is only a few
      micrometers in length. Bacteria do not have nucleosomes and little is known about
      the arrangement of the chromosome inside a prokaryotic cell. RESULTS: We have
      investigated the arrangement of chromosomal DNA within the bacterium Bacillus
      subtilis by using fluorescence microscopy to visualize two sites on the
      chromosome simultaneously in the same cell. Indirect immunofluorescence with
      antibodies against the chromosome partition protein Spo0J were used to visualize
      the replication origin region of the chromosome. Green fluorescent protein fused
      to the lactose operon repressor Lacl was used to decorate tandem copies of the
      lactose operon operator lacO. A cassette of tandem operators was separately
      inserted into the chromosome near the origin (359 degrees), near the replication
      terminus (181 degrees), or at two points in between (90 degrees and 270 degrees).
      The results show that the layout of the chromosome is dynamic but is principally
      arranged with the origin and terminus maximally apart and the quarter points of
      the chromosome in between. CONCLUSIONS: The use of cytological methods to
      visualize two chromosomal sites in the same cell has provided a glimpse of the
      arrangement of a bacterial chromosome. We conclude that, to a first
      approximation, the folding of the bacterial chromosome is consistent with, and
      may preserve, the linear order of genes on the DNA.

PMID- 9778527
TI  - Cohesion between sister chromatids must be established during DNA replication.
AB  - BACKGROUND: Cohesion between sister chromatids, which opposes the splitting force
      exerted by the mitotic spindle during metaphase, is essential for their
      segregation to opposite poles of the cell during anaphase. In Saccharomyces
      cerevisiae, cohesion depends on a set of chromosomal proteins called cohesins,
      which include structural maintenance of chromosomes 1p (Smc1p), Smc3p and sister
      chromatid cohesion 1p (Scc1p). Strains with mutations in the genes encoding these
      proteins separate sister chromatids prematurely and fail to align them in
      metaphase. This leads to missegregation of chromosomes in the following anaphase.
      RESULTS: In a normal cell cycle, Scc1p was synthesized and recruited to
      chromosomes at the onset of S phase. Using cells that expressed Scc1p exclusively
      from a galactose-inducible promoter, we showed that if Scc1p was synthesised only
      after completion of S phase, it still bound to chromosomes but failed to promote
      sister chromatid cohesion. CONCLUSIONS: Cohesion between sister chromatids must
      be established during DNA replication, possibly following the passage of a
      replication fork. Furthermore, Scc1p (and other cohesins) are needed both for
      maintaining cohesion during mitosis and for establishing it during S phase.
      Establishment of sister chromatid cohesion is therefore an essential but hitherto
      neglected aspect of S phase.

PMID- 9778526
TI  - The dynactin complex is required for cleavage plane specification in early
      Caenorhabditis elegans embryos.
AB  - BACKGROUND: During metazoan development, cell diversity arises primarily from
      asymmetric cell divisions which are executed in two phases: segregation of
      cytoplasmic factors and positioning of the mitotic spindle - and hence the
      cleavage plane -relative to the axis of segregation. When polarized cells divide,
      spindle alignment probably occurs through the capture and subsequent shortening
      of astral microtubules by a site in the cortex. RESULTS: Here, we report that
      dynactin, the dynein-activator complex, is localized at cortical microtubule
      attachment sites and is necessary for mitotic spindle alignment in early
      Caenorhabditis elegans embryos. Using RNA interference techniques, we eliminated
      expression in early embryos of dnc-1 (the ortholog of the vertebrate gene for
      p150(Glued)) and dnc-2 (the ortholog of the vertebrate gene for p50/Dynamitin).
      In both cases, misalignment of mitotic spindles occurred, demonstrating that two
      components of the dynactin complex, DNC-1 and DNC-2, are necessary to align the
      spindle. CONCLUSIONS: Dynactin complexes may serve as a tether for dynein at the
      cortex and allow dynein to produce forces on the astral microtubules required for
      mitotic spindle alignment.

PMID- 9778528
TI  - Localization of mitochondrial large ribosomal RNA in germ plasm of Xenopus
      embryos.
AB  - In Xenopus, factors with the ability to establish the germ line are localized in
      the vegetal pole cytoplasm, or germ plasm, of the early embryo [1-3]. The germ
      plasm of Xenopus, and of many other animal species including Drosophila, contains
      electron-dense germinal granules which may be essential for germ-line formation
      [4-5]. Several components of the germinal granules have so far been identified in
      Drosophila [6-10]. One of these is mitochondrial large ribosomal RNA (mtlrRNA),
      which is present in the germinal granules (polar granules) during the cleavage
      stage until the formation of the germ-line progenitors or pole cells [8-9].
      MtlrRNA has been identified as a factor that induces pole cells in embryos that
      have been sterilized by ultraviolet radiation [11]. The reduction of mtlrRNA in
      germ plasm by injecting anti-mtlrRNA ribozymes into embryos leads to the
      inability of these embryos to form pole cells [12]. These observations clearly
      show that mtlrRNA is essential for pole cell formation in Drosophila. Here, we
      report that mtlrRNA is enriched in germ plasm of Xenopus embryos from the four
      cell stage to the blastula. Furthermore, our electron microscopic studies show
      that this mtlrRNA is present in the germinal granules during these stages. Thus,
      mtlrRNA is a common component of germinal granules in Drosophila and Xenopus,
      suggesting that the mtlrRNA has a role in germ-line development across
      phylogenetic boundaries.

PMID- 9778529
TI  - A role for Bruton's tyrosine kinase (Btk) in platelet activation by collagen.
AB  - Bruton's tyrosine kinase (Btk) is essential for normal B-cell receptor
      signalling. The lack of expression of functional Btk in humans leads to the B
      cell deficiency X-linked agammaglobulinaemia (XLA). We report here that Btk is
      also important for signalling via the collagen receptor glycoprotein VI (GPVI) in
      platelets. GPVI is coupled to the Fc receptor gamma chain (FcRgamma). The
      FcRgamma-chain contains a consensus sequence known as the immune-receptor
      tyrosine-based activation motif (ITAM). Tyrosine phosphorylation of the ITAM upon
      GPVI stimulation is the initial step in the regulation of phospholipase C gamma2
      (PLCgamma2) isoforms via the tyrosine kinase p72(Syk) (Syk) in platelets. Here we
      show that collagen and a collagen-related peptide (CRP), which binds to GPVI but
      does not bind to the integrin alpha2beta1, induced Btk tyrosine phosphorylation
      in platelets. Aggregation, dense granule secretion and calcium mobilisation were
      significantly diminished but not completely abolished in platelets from XLA
      patients in response to collagen and CRP. These effects were associated with a
      reduction in tyrosine phosphorylation of PLCgamma2. In contrast, aggregation and
      secretion stimulated by thrombin in Btk-deficient platelets were not
      significantly altered. Our results demonstrate that Btk is important for collagen
      signalling via GPVI, but is not essential for thrombin-mediated platelet
      activation.

PMID- 9778530
TI  - Caspases and programmed cell death in the hypersensitive response of plants to
      pathogens.
AB  - The hypersensitive response (HR) is induced by certain plant pathogens and
      involves programmed cell death (PCD) to restrict the spread of pathogens from the
      infection site [1]. Concurrent with the induction of cell death, the host
      activates a defense response [2]. The cell death associated with the HR in
      several plant-pathogen systems has morphological similarities to animal apoptosis
      [3,4], which suggests that cell death mechanisms in plants and animals may share
      common components that lead to similar cellular events. Caspases are conserved
      cysteine proteases that regulate animal PCD [5]; caspase activity or an
      involvement of caspases in cell death has yet to be reported in plants. In this
      work, we investigated the participation of caspases in HR cell death. Caspase
      specific peptide inhibitors, Ac-YVAD-CMK [6] and Ac-DEVD-CHO [7], could abolish
      bacteria-induced plant PCD but did not significantly affect the induction of
      other aspects of HR, such as the expression of defense genes. This result
      confirmed our previous model that cell death can be uncoupled from defense gene
      activation during HR [8]. Caspase-like proteolytic activity was detected in
      tobacco tissues that were developing HR following infection with tobacco mosaic
      virus (TMV). Our results provide evidence for the presence of caspase-like plant
      protease(s) that participate in HR cell death.

PMID- 9778531
TI  - The ras recruitment system, a novel approach to the study of protein-protein
      interactions.
AB  - The yeast two-hybrid system represents one of the most efficient approaches
      currently available for identifying and characterizing protein-protein
      interactions [1-4]. Although very powerful, this procedure exhibits several
      problems and inherent limitations [5]. A new system, the Sos recruitment system
      (SRS), was developed recently [6] based on a different readout from that of the
      two-hybrid system [6-8]. SRS overcomes several of the limitations of the two
      hybrid system and thus serves as an attractive alternative for studying protein
      protein interactions between known and novel proteins. Nevertheless, we
      encountered a number of problems using SRS and so have developed an improved
      protein recruitment system, designated the Ras recruitment system (RRS), based on
      the absolute requirement that Ras be localized to the plasma membrane for its
      function [9-10]. Ras membrane localization and activation can be achieved through
      interaction between two hybrid proteins. We have demonstrated the effectiveness
      of the novel RRS system using five different known protein-protein interactions
      and have identified two previously unknown protein-protein interactions through a
      library screening protocol. The first interaction (detailed here) is between
      JDP2, a member of the basic leucine zipper (bZIP) family, and C/EBPgamma, a
      member of the CCAAT/enhancer-binding protein (C/EBP) family. The second
      interaction is between the p21-activated protein kinase Pak65 and a small G
      protein (described in the accompanying paper by Aronheim et al. [11]). The RRS
      system significantly extends the usefulness of the previously described SRS
      system and overcomes several of its limitations.

PMID- 9778532
TI  - Chp, a homologue of the GTPase Cdc42Hs, activates the JNK pathway and is
      implicated in reorganizing the actin cytoskeleton.
AB  - The p21-activated protein kinases (PAKs) are activated through direct interaction
      with the GTPases Rac and Cdc42Hs, which are implicated in the control of the
      mitogen-activated protein kinase (MAP kinase) c-Jun N-terminal kinase (JNK) and
      the reorganization of the actin cytoskeleton [1-3]. The exact role of the PAK
      proteins in these signaling pathways is not entirely clear. To elucidate the
      biological function of Pak2 and to identify its molecular targets, we used a
      novel two-hybrid system, the Ras recruitment system (RRS), that aims to detect
      protein-protein interactions at the inner surface of the plasma membrane
      (described in the accompanying paper by Broder et al. [4]). The Pak2 regulatory
      domain (PakR) was fused at the carboxyl terminus of a RasL61 mutant protein and
      screened against a myristoylated rat pituitary cDNA library. Four clones were
      identified that interact specifically with PakR and three were subsequently shown
      to encode a previously unknown homologue of the GTPase Cdc42Hs. This
      approximately 36 kDa protein, designated Chp, exhibits an overall sequence
      identity to Cdc42Hs of approximately 52%. Chp contains two additional sequences
      at the amino and carboxyl termini that are not found in any known GTPase. The
      amino terminus contains a polyproline sequence, typically found in Src homology 3
      (SH3)-binding domains, and the carboxyl terminus appears to be important for Pak2
      binding. Results from the microinjection of Chp into cells implicated Chp in the
      induction of lamellipodia and showed that Chp activates the JNK MAP kinase
      cascade.

PMID- 9778534
TI  - First class stamps 

PMID- 9778535
TI  - Combinatorial chemistry.

PMID- 9778533
TI  - A nematode kinesin required for cleavage furrow advancement.
AB  - Dividing cells need to coordinate the separation of chromosomes with the
      formation of a cleavage plane. There is evidence that microtubule bundles in the
      interzone region of the anaphase spindle somehow control both the location and
      the assembly of the cleavage furrow [1-3]. A microtubule motor that concentrates
      in the interzone, MKLP1, has previously been implicated in the assembly of both
      the metaphase spindle and the cleavage furrow [4-6]. To gain insight into
      mechanisms that might underlie interdependence of the spindle and the cleavage
      furrow, we used RNA-mediated interference (RNAi) to study the effects of
      eliminating MKLP1 from Caenorhabditis elegans embryos. Surprisingly, in
      MKLP1(RNAi) embryos, spindle formation appears normal until late anaphase.
      Microtubule bundles form in the spindle interzone and the cleavage furrow
      assembles; anaphase and cleavage furrow ingression initially appear normal. The
      interzone bundles do not gather into a stable midbody, however, and furrow
      contraction always fails before complete closure. This sequence of relatively
      normal mitosis and a late failure of cytokinesis continues for many cell cycles.
      These and additional results suggest that the interzone microtubule bundles need
      MKLP1 to encourage the advance and stable closure of the cleavage furrow.

PMID- 9778536
TI  - Model organisms.

PMID- 9778537
TI  - Times they are a' changin' 

PMID- 9778538
TI  - Fas 

PMID- 9778539
TI  - Integrins during muscle development and in muscular dystrophies.
AB  - Cellular interactions with the extracellular matrix (ECM) have been shown to be
      important for a number of developmental events from the time of fertilization up
      till the maturation of the organism. In the following review we will discuss what
      is currently known about these interactions with special emphasis on the role of
      integrins during the formation of skeletal muscle. The importance of cell-ECM
      interactions will also be illustrated by a discussion of what happens when these
      interactions go awry, as happens in muscular dystrophies.

PMID- 9778540
TI  - Electrosigmoidogram in the various pathologic conditions of the sigmoid colon.
AB  - The current study investigates the electrosigmoidographic (ESG) patterns in 50
      patients with sigmoid colon pathologies and 10 healthy controls. Three electrodes
      were applied to the skin of the lower abdomen and the reference electrode was
      placed on the lower limb. Ulcerative colitis patients showed a "tachyarrhythmic"
      ESG; the PPs had a higher frequency with a lower amplitude and velocity than the
      normal controls. The sigmoid diverticulitis exhibited a "bradyarrhythmic"
      pattern; the PP variables were lower than normal. The PPs in sigmoid polyposis
      were "scarce" and were recorded only occasionally. In sigmoid colon cancer, the
      electric waves were normal proximal to the tumor and absent opposite and distal
      to it; a "silent" ESG was recorded in sigmoidectomy patients. Various ESG
      patterns were recordable in the different pathologic conditions of the sigmoid
      colon. It is thus suggested that percutaneous ESG can be included as an
      investigative tool in the diagnosis of sigmoid colon pathologies. The method is
      simple, easy, non-invasive and non-radiologic.

PMID- 9778542
TI  - Use of spectral turbulence analysis for the identification of patients at high
      risk for ventricular fibrillation and sudden death in patients with hypertrophic
      cardiomyopathy.
AB  - Hypertrophic cardiomyopathy carries an increased risk of sudden death. The aim of
      the present study was to assess the predictive value of the signal-averaged ECG,
      analysed in the time domain and using a new method, spectral turbulence analysis,
      for the identification of high-risk patients. Two-hundred and forty-six patients
      with hypertrophic cardiomyopathy were studied. During a mean follow-up of 68 +/-
      17 months, 17 patients died suddenly. Patients with sudden death (SD) and/or a
      history of ventricular fibrillation (VF; n = 25) were compared to patients
      without SD/VF (n = 221) and to patients without any recognised risk factors for
      SD (n = 82). There were no differences in mean values of the time domain or
      spectral turbulence parameters analysed between patients in the SD/VF group and
      the patients without SD/VF or in the low-risk group. It is concluded that the
      clinical usefulness of the signal-averaged ECG, analysed in the time domain or as
      spectral turbulence analysis, is limited in identifying high-risk patients with
      hypertrophic cardiomyopathy.

PMID- 9778541
TI  - Low prevalence of hepatitis C virus antibodies and RNA in patients with
      myocarditis and dilated cardiomyopathy.
AB  - We investigated the prevalence of hepatitis C virus in patients with dilated
      cardiomyopathy (DCM) and myocarditis in comparison to a control group of patients
      suffering from noninflammatory cardiac diseases such as aortic stenosis. In
      contrast to the results of previous studies on small numbers of patients, no
      significant difference in the prevalence of hepatitis C infections was observed.
      Our data suggest that HCV is not an important causal agent for myocarditis and
      DCM.

PMID- 9778544
TI  - Plasma B-type natriuretic peptide measurement in a multiphasic health screening
      program.
AB  - The aim of this study was to determine whether measurement of plasma levels of
      atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) is an
      efficacious method to predict patients with heart disease irrespective of left
      ventricular function in a multiphasic health screening program. We have examined
      whether patients with various heart disease selected by physical examination,
      ECG, and chest X-rays can be identified by plasma levels of ANP and BNP. We
      examined 481 consecutive subjects who visited our checkup clinic for a
      multiphasic health screening test. By routine methods, among the 481 subjects, 13
      were found to have some form of heart disease (old myocardial infarction, 2;
      cardiomyopathy, 2; valvular heart disease, 2; hypertensive heart disease, 5, and
      lone atrial fibrillation, 2). Sensitivity, specificity, and quintile analysis for
      identification of the patients with heart disease were determined by various
      cutoff levels of plasma ANP and BNP. Receiver operating characteristic (ROC)
      curves were constructed for the identification of these patients. A plasma BNP
      level of 40 pg/ml had a sensitivity of 85% and a specificity of 92% for heart
      disease detection. The area under the ROC curve for BNP was significantly greater
      than that for ANP (0.94 vs. 0.81; p < 0.001). A plasma BNP level of 13 pg/ml or
      less gave a 100% negative prediction value for heart disease. Plasma BNP
      concentration is a useful biochemical marker for the screening of asymptomatic
      patients with heart disease due to various etiologies from large population
      samples.

PMID- 9778543
TI  - Lack of evidence for a pathogenic role of Chlamydia pneumoniae and
      cytomegalovirus infection in coronary atheroma formation.
AB  - Atherosclerotic cardiovascular disease is generally accepted to be the result of
      metabolic disturbances. However, recent studies have suggested an infectious
      agent, especially Chlamydia pneumoniae or cytomegalovirus, to be involved in the
      pathogenesis of atherosclerosis. Atherosclerotic plaque specimens obtained from
      patients with coronary disease either by balloon dilatation catheter (13 cases)
      or atherectomy (16 patients) were examined for the presence of C. pneumoniae and
      cytomegalovirus. Using two primer pairs for C. pneumoniae, two primer pairs for
      the identification of unknown bacteria and primer pairs for the detection of
      immediate early gene E2 and the late genomic region of cytomegalovirus, we were
      unable to detect the suspected agents. The absence of C. pneumoniae, other
      bacteria and CMV in coronary atheromas is against the hypothesis of a
      pathogenetic role of these agents in coronary atheroma formation in the patients
      studied.

PMID- 9778546
TI  - Fibrosis, myocyte degeneration and heart failure in chronic experimental aortic
      regurgitation.
AB  - Myocardial fibrosis and myocyte degeneration have been reported in patients with
      chronic aortic regurgitation (AR), and may be related to the pathophysiology of
      congestive heart failure (CHF) in this disease. To define the relationship
      between myocardial histopathologic variations and CHF in chronic AR, we performed
      gross and microscopic evaluations of postmortem tissue from a rabbit model of
      chronic AR manifesting left ventricular (LV) responses to AR similar to those in
      humans. Moderate-to-severe chronic AR (echocardiographic regurgitant fraction =
      52 +/- 13%) was induced by closed-chest aortic valve perforation in 11 New
      Zealand White rabbits; 5 control rabbits were sham operated. Six of the 11 AR
      rabbits died 1.5 +/- 0.8 years (range 0.6-2.8 years) after AR induction; all 6
      had gross and histologic anatomic evidence of CHF at necropsy. The remaining 5 AR
      rabbits survived until sacrifice at 2.9 +/- 0.1 years of AR; none had pathologic
      evidence of CHF. Cardiac hypertrophy and the extent of LV fibrosis and myocyte
      necrosis all were greatest among the 6 AR CHF rabbits. No inflammatory response
      was apparent in any animal. Moderate-to-severe chronic experimental AR frequently
      results in CHF which is strongly associated with myocardial fibrosis and
      necrosis, without evidence of inflammation. These histopathologic variations may
      be pathophysiologically related to CHF development.

PMID- 9778545
TI  - Distribution of calcitonin gene-related peptide, atrial natriuretic peptide and
      neuropeptide Y in the rat heart.
AB  - Calcitonin gene-related peptide (CGRP) is a novel neuropeptide, predicted on the
      basis of structural analysis of the rat calcitonin gene. It is a neurotransmitter
      which has been suggested to take part in sensory transmission. In this study, we
      have examined the distribution of this peptide, alpha-atrial natriuretic peptide
      immunoreactivity (irANP) and neuropeptide Y (NPY) within different regions of the
      rat heart. Attempts were also made to compare the distributions of these peptides
      in the regions examined, through different methods of immunocytochemistry and
      further comparing these results with those obtained through radioimmunoassay. The
      distributions of the peptides in the atria were similar to results obtained with
      radioimmunoassay, but there were no myocytes containing irANP in the ventricles
      with immunocytochemistry as opposed to radioimmunoassay. While the staining
      obtained for irANP in the atrium was more intense in the right, CGRP and NPY
      nerve fibres were two to three times more abundant in the left atrium. The high
      local concentration of a vasoconstrictor peptide in the region of coronary
      vessels may suggest that it is involved in the control of vascular smooth muscle
      tone. The method of choice with the immunocytochemical studies was that of the
      susa wax technique for irANP. Caution should therefore be observed when
      interpreting results based only on a single staining technique.

PMID- 9778547
TI  - Predictors of death and other cardiac events within 2 years after coronary artery
      bypass grafting.
AB  - RESULTS: In 1,841 patients who underwent coronary artery bypass grafting (CABG)
      we evaluated risk indicators for death and other cardiac events during 2 years of
      follow-up. Independent predictors of death were: a history of congestive heart
      failure, diabetes mellitus and renal dysfunction prior to CABG. Independent
      predictors of death, acute myocardial infarction (AMI), CABG or percutaneous
      transluminal coronary angioplasty (PTCA) were: a small body surface area, a
      history of congestive heart failure, diabetes mellitus and smoking prior to CABG.
      Independent predictors of death, AMI, CABG, PTCA or rehospitalization for a
      cardiac reason were: angina functional class, previous AMI, a history of
      congestive heart failure and renal dysfunction prior to CABG. CONCLUSION: When
      using various definitions of a cardiac event after CABG, various risk indicators
      for death or such an event can be found. Our data suggest that anamnestic
      information prior to CABG indicating a depressed myocardial function or severe
      myocardial ischemia are more important predictors of outcome than the information
      gained from cardioangiography.

PMID- 9778548
TI  - Morphometric and histologic assessment of remodeling associated with restenosis
      after percutaneous transluminal coronary angioplasty.
AB  - The role of remodeling in restenosis of coronary arteries on which percutaneous
      transluminal coronary angioplasty (PTCA) had been performed was investigated. At
      autopsy, presence (n = 6) or absence of restenosis (n = 5) based on the cross
      sectional area of stenosis was determined in 11 coronary lesions. Remodeling was
      defined as a ratio of the artery area at the PTCA site to that at the reference
      site of <1.0. According to this definition, remodeling had occurred in all of the
      lesions in the restenosis group, and in only 1 lesion in the group with no
      restenosis which had the least residual plaque (p < 0.05). Dense caps of collagen
      fibers in the adventitia in the vicinity of the disrupted internal elastic
      laminae were present in all of the remodeling lesions. We suggest that
      remodeling, which results in adventitial scarring, is one of the major causative
      factors of restenosis.

PMID- 9778549
TI  - Parasympathetic tone affects electrocardiographic preconditioning during right
      coronary angioplasty.
AB  - We investigated whether parasympathetic tone may affect ischemic preconditioning
      in terms of ST segment alteration during coronary angioplasty. Coronary balloon
      angioplasty was performed in 19 patients with angina and isolated right coronary
      artery disease. Parasympathetic tone was assessed by frequency domain parameters
      of heart rate variability using 24-hour electrocardiographic recordings obtained
      before angioplasty. Logistic regression analysis showed the high frequency
      component to be an independent predictor of the change in ST elevation induced by
      the second balloon inflation. An increase in parasympathetic tone was related to
      ischemic preconditioning with respect to the electrocardiographic alterations
      observed in these patients.

PMID- 9778552
TI  - Thallium-201 for detection of myocardial viability: comparison of early
      postexercise reinjection and imaging with 4 and 18-24 hours redistribution
      imaging.
AB  - To evaluate the efficacy of an early 201Tl reinjection and imaging protocol for
      reducing the need for conventional 4-hour or optimal 24-hour redistribution
      imaging (RI) and detecting of myocardial viability, we compared the results of
      early postexercise Tl reinjection and imaging with those of 4- and 24-hour RI in
      74 consecutive patients aged 55 +/- 9 years (mean +/- SD) who were assessed for
      myocardial ischemia. One millicurie of Tl was injected promptly after completion
      of the initial postexercise imaging (PEX) and three additional sets of images
      were acquired 1, 4 and 18-24 h later. A total of 2,368 segments were evaluated.
      On PEX, 390 (17%) segments showed defects, of which 287 (74%) showed enhanced Tl
      uptake at 1-hour RI; 89 (23%) did not change and 14 (4%) showed reverse
      redistribution. Of the 103 persistent defects, only 27 (7%) showed further fill
      in of Tl; 62 (16%) segments showed reverse redistribution at 4-hour RI while at
      18- to 24-hour RI 17 (4%) and 47 (12%) segments showed further fill-in of Tl and
      reverse redistribution, respectively. Finally, after analysis of 4- and 18- to 24
      hour RI, the diagnosis changed from myocardial necrosis to ischemia in only 2
      (3%) patients. In conclusion, these results suggest that by eliminating the need
      for an additional delayed set of images for detection of myocardial viability,
      this protocol reduces the total investigation procedure, is more convenient for
      the patient, increases patient turnover and expedites the decision-making
      process.

PMID- 9778550
TI  - Depressed plasma platelet-activating factor acetylhydrolase in patients
      presenting with acute myocardial infarction.
AB  - Cell membrane phospholipids, including platelet-activating factor (PAF),
      participate in the pathogenesis of acute myocardial infarction (AMI). The plasma
      level of PAF acetylhydrolase (AH) was determined in 18 patients at presentation
      with AMI before thrombolysis, and the administration of adjunctive therapy, and
      compared with 13 healthy controls. Plasma levels of PAF-AH were significantly
      lower in the AMI patients (23.15 +/- 1.75 nmol/min/ml) than in the controls
      (30.43 +/- 2.13 nmol/min/ml; p = 0.027). Considering normal plasma levels of PAF
      and lyso-PAF, and lack of evidence that anti-PAF antibodies are really beneficial
      in myocardial ischemia-reperfusion, it is reasonable to speculate that an
      inability of systemic PAF to 'turn on' PAF-AH enzymatic activity could contribute
      substantially to the observed events. Decreased PAF-AH activity in AMI patients
      may represent not a consequence, but rather, a risk factor for the development of
      acute coronary syndromes.

PMID- 9778551
TI  - Hyperbaric oxygen and thrombolysis in myocardial infarction: the 'HOT MI'
      randomized multicenter study.
AB  - In a previous pilot study, we demonstrated that adjunctive treatment with
      hyperbaric oxygen (HBO) appears to be feasible and safe in patients with acute
      myocardial infarction (AMI) and may result in an attenuated rise in creatine
      phosphokinase (CPK), more rapid resolution of pain and ST changes. This
      randomized multicenter trial was organized to further assess the safety and
      feasibility of this treatment in human subjects. Patients with an AMI treated
      with recombinant tissue plasminogen activator (rTPA) or streptokinase (STK), were
      randomized to treatment with HBO combined with either rTPA or STK, or rTPA or STK
      alone. An analysis included 112 patients, 66 of whom had inferior AMIs (p = NS).
      The remainder of the patients had anterior AMIs. The mean CPK at 12 and 24 h was
      reduced in the HBO patients by approximately 7.5% (p = NS). Time to pain relief
      was shorter in the HBO group. There were 2 deaths in the control and 1 in those
      treated with HBO. The left ventricle ejection fraction (LVEF) on discharge was
      51.7% in the HBO group as compared to 48.4% in the controls (p = NS). The LVEF of
      the controls was 43.4 as compared to 47.6 for those treated, approximately 10%
      better (no significant difference). Treatment with HBO in combination with
      thrombolysis appears to be feasible and safe for patients with AMI and may result
      in an attenuated CPK rise, more rapid resolution of pain and improved ejection
      fractions. More studies are needed to assess the benefits of this treatment.

PMID- 9778553
TI  - Left ventricular wall thickening does occur in elite power athletes with or
      without anabolic steroid Use.
AB  - Reports on the occurrence of left ventricular wall thickening in resistance
      trained athletes have rejected the possibility for this physiological adaptation
      to occur without concomitant anabolic steroid abuse. Others have concluded short
      bursts of arterial hypertension that occur with maximal weight lifting are not
      sufficient to induce left ventricular wall thickening, and left ventricular wall
      thickness >/=13 mm should not be found in pure resistance-trained athletes.
      Therefore, we examined 4 elite resistance-trained athletes by two-dimensional
      echocardiography. In addition, we retrospectively examined the individual left
      ventricular dimensions of 13 bodybuilders from our previous echocardiographic
      studies. All 4 elite resistance-trained athletes had left ventricular wall
      thicknesses beyond 13 mm. One of the elite bodybuilders has the largest left
      ventricular wall thickness (16 mm) ever reported in a power athlete.
      Retrospectively, 43% of the drug-free bodybuilders and 100% of the steroid users
      had left ventricular wall thickness beyond the normal range of 11 mm. In
      addition, 1 drug-free subject and 3 steroid users were beyond the critical mark
      of 13 mm. No subjects demonstrated diastolic dysfunction. In contrast to previous
      reports, we have demonstrated that left ventricular wall thicknesses >/=13 mm can
      be found routinely in elite resistance-trained athletes. The use of anabolic
      steroids concomitant with intensive resistance exercise does appear to augment
      left ventricular size without dysfunction. Anabolic steroids may accelerate left
      ventricular wall thickening indirectly by increasing strength, thus augmenting
      the pressor response.

PMID- 9778554
TI  - Evidence of apoptosis induced by myocardial ischemia: A case of ventricular
      septal rupture following acute myocardial infarction.
AB  - Recent studies have reported that apoptosis may be induced by reperfusion injury
      following ischemia in cardiomyocytes. We present a case with evidence of
      apoptosis induced by myocardial ischemia without reperfusion. DNA fragmentation
      was demonstrated in the nuclei of the myocardial cells surrounding the
      ventricular septal rupture following acute myocardial infarction without
      reperfusion in the infarct-related left anterior descending coronary artery. This
      finding suggests that ischemia without reperfusion may induce apoptosis in
      myocardial cells.

PMID- 9778561
TI  - Preface 

PMID- 9778555
TI  - Acupuncture treatment for angina.

PMID- 9778562
TI  - N-acetyl aspartate: a marker for neuronal loss or mitochondrial dysfunction.

PMID- 9778564
TI  - Introduction 

PMID- 9778563
TI  - Landmarks in the application of 13C-magnetic resonance spectroscopy to studies of
      neuronal/glial relationships.
AB  - The development of the use of carbon isotopes as metabolic tracers is briefly
      described. 13C-labelled precursors (13CO2, 13CH4) first became available in 1940
      and were studied in microorganisms, but their use was limited by very low
      enrichments and lack of suitable analytical equipment. More success was achieved
      with 11C and especially 14C, as these radioactive tracers did not need to be
      highly enriched. Although the stable 13C isotope can be used at a low percentage
      enrichment in mass spectrometry, its application to magnetic resonance
      spectroscopy (MRS) requires very highly enriched precursors, due to its low
      natural abundance and low sensitivity. Despite such limitations, however, the
      great advantage of 13C-MRS lies in its exquisite chemical specificity, in that
      labelling of different carbon atoms can be distinguished within the same
      molecule. Effective exploitation became feasible in the early 1970s with the
      advent of stable instruments, Fourier transform 13C-MRS, and the availability of
      highly enriched precursors. Reports of its use in brain research began to appear
      in the mid-1980s. The applications of 13C isotopomer analysis to research on
      neuronal/glial relationships are reviewed. The presence of neighbouring 13C
      labelled atoms affects the appearance of the resonances (splitting due to C-C
      coupling), and so allows for unique quantification of rates through different and
      possibly competing pathways. Isotopomer patterns in resonances labelled from a
      combination of [1-13C]glucose and [1, 2-13C2]acetate have revealed aspects of
      neuronal/glial metabolic trafficking on depolarization and under hypoxic
      conditions in vitro. This approach has now been applied to in vivo studies on
      inhibition of glial metabolism using fluoroacetate. The results confirm the glial
      specificity of the toxin and demonstrate that it does not affect entry of
      acetate. When the glial TCA cycle is inhibited, the ability of the glia to
      participate in the glutamate/glutamine cycle remains unimpaired, in that
      labelling of glutamine, which can only be derived from neuronal metabolism of
      glucose, persists. The results also confirmed earlier evidence that part of the
      GABA transmitter pool is derived from glial glutamine.

PMID- 9778565
TI  - Evidence supporting the existence of an activity-dependent astrocyte-neuron
      lactate shuttle.
AB  - Mounting evidence from in vitro experiments indicates that lactate is an
      efficient energy substrate for neurons and that it may significantly contribute
      to maintain synaptic transmission, particularly during periods of intense
      activity. Since lactate does not cross the blood-brain barrier easily, blood
      borne lactate cannot be a significant source. In vitro studies by several
      laboratories indicate that astrocytes release large amounts of lactate. In 1994,
      we proposed a mechanism whereby lactate could be produced by astrocytes in an
      activity-dependent, glutamate-mediated manner. Over the last 2 years we have
      obtained further evidence supporting the notion that a transfer of lactate from
      astrocytes to neurons might indeed take place. In this article, we first review
      data showing the presence of mRNA encoding for two monocarboxylate transporters,
      MCT1 and MCT2, in the adult mouse brain. Second, by using monoclonal antibodies
      selectively directed against the two distinct lactate dehydrogenase isoforms,
      LDH1 and LDH5, a specific cellular distribution between neurons and astrocytes is
      revealed which suggests that a population of astrocytes is a lactate 'source'
      while neurons may be a lactate 'sink'. Third, we provide biochemical evidence
      that lactate is interchangeable with glucose to support oxidative metabolism in
      cortical neurons. This set of data is consistent with the existence of an
      activity-dependent astrocyte-neuron lactate shuttle for the supply of energy
      substrates to neurons.

PMID- 9778567
TI  - Comparison of lactate and glucose metabolism in cultured neocortical neurons and
      astrocytes using 13C-NMR spectroscopy.
AB  - In cerebral cortical neurons, synthesis of the tricarboxylic acid (TCA) cycle
      derived amino acids, glutamate and aspartate as well as the neurotransmitter of
      these neurons, gamma-aminobutyrate (GABA), was studied incubating the cells in
      media containing 0.5 mM [U-13C]glucose in the absence or presence of glutamine
      (0.5 mM). Lyophilized cell extracts were analyzed by 13C nuclear magnetic
      resonance (NMR) spectroscopy and HPLC. The present findings were compared to
      results previously obtained using 1.0 mM [U-13C]lactate as the labeled substrate
      for the neurons. Regardless of the amino acids studied, incubation periods of 1
      and 4 h resulted in identical amounts of 13C incorporated. Furthermore, the
      metabolism of lactate was studied under analogous conditions in cultured cerebral
      cortical astrocytes. The incorporation of 13C from lactate into glutamate was
      much lower in the astrocytes than in the neurons. In cerebral cortical neurons
      the total amount of 13C in GABA, glutamate and aspartate was independent of the
      labeled substrate. The enrichment in glutamate and aspartate was, however, higher
      in neurons incubated with lactate. Thus, lactate appears to be equivalent to
      glucose with regard to its access to the TCA cycle and subsequent labeling of
      glutamate, aspartate and GABA. It should be noted, however, that incubation with
      lactate in place of glucose led to lower cellular contents of glutamate and
      aspartate. The presence of glutamine affected the metabolism of glucose and
      lactate differently, suggesting that the metabolism of these substrates may be
      compartmentalized.

PMID- 9778566
TI  - Lactate transport by cortical synaptosomes from adult rat brain: characterization
      of kinetics and inhibitor specificity.
AB  - Since lactate released by glial cells may be a key substrate for energy in
      neurons, the kinetics for the uptake of L-[U-14C]lactate by cortical synaptic
      terminals from 7- to 8-week-old rat brain were determined. Lactate uptake was
      temperature-dependent, and increased by 64.9% at pH 6.2, and decreased by 43.4%
      at pH 8.2 relative to uptake at pH 7.3. Uptake of monocarboxylic acids was
      saturable with increasing substrate concentration. Eadie-Hofstee plots of the
      data gave evidence of two carrier-mediated uptake mechanisms with a high-affinity
      Km of 0.66 mM and Vmax of 3.66 mM for pyruvate, and a low-affinity system with a
      Km of 9.9 mM for both lactate and pyruvate and Vmax values of 16.6 and 23.1
      nmol/30 s/mg protein for lactate and pyruvate, respectively. Saturable uptake was
      seen in the presence of 10 mM alpha-cyano-4-hydroxycinnamate. Lactate transport
      by synaptic terminals was much more sensitive to inhibition by sulfhydryl
      reagents than transport in astrocytes. Addition of 0.5 and 2 mM mersalyl
      decreased the uptake of 1 mM lactate by synaptic terminals by 59.3 and 66.37%,
      respectively. Pyruvate moderately decreased lactate transport, whereas 3
      hydroxybutyrate had little effect. Quercetin, an inhibitor of lactate release,
      had little effect on the content of 14C lactate in synaptic terminals, supporting
      the concept that the majority of lactate produced within brain is from glial
      cells. Oxidation of L-[U-14C]lactate by synaptosomes was saturable, and yielded a
      Km of 1.23 mM and a Vmax of 116 nmol/h/mg protein. Overall the studies show that
      synaptic terminals from adult brain have a high capacity for transport and
      oxidation of lactate, consistent with the proposed role for this compound in
      metabolic trafficking in brain. Furthermore, the data provide kinetic evidence of
      two carrier-mediated mechanisms for monocarboxylic acid transport by synaptosomes
      and demonstrate that uptake of lactate by synaptic terminals is regulated
      differently than transport by astrocytes. Uptake of lactate by synaptic terminals
      also has differences from the systems described for neurons.

PMID- 9778568
TI  - Functional energy metabolism: in vivo 13C-NMR spectroscopy evidence for coupling
      of cerebral glucose consumption and glutamatergic neuronalactivity.
AB  - The use of in vivo 13C nuclear magnetic resonance spectroscopy (NMR) has
      established the pathways of functional interaction between neurons and astrocytes
      in the mammalian brain and enabled quantitation of these fluxes. A mathematical
      model of glutamate, glutamine and ammonia metabolism in the brain has been
      developed, under the constraints of carbon and nitrogen mass balance, allowing
      the direct and quantitative comparison of in vivo 13C- and 15N-NMR data. Using
      this model and 13C-NMR data, the authors have separated the neurotransmitter
      cycling and detoxification components of glutamine synthesis by measuring the
      rate of glutamine synthesis under normal and hyperammonaemic conditions in the
      rat brain cortex in vivo. In addition, the simultaneous measurement of the rates
      of oxidative glucose metabolism and glutamate neurotransmitter cycling in the rat
      brain cortex has shown that over a range of EEG activity (from isoelectric up to
      near-resting levels) the stoichiometry between glucose metabolism and glutamate
      cycling is close to 1:1. Under mild anesthesia, cortical glucose oxidation
      coupled to glutamatergic synaptic activity accounts for over 80% of total glucose
      oxidation. Previously, changes in cerebral glucose metabolism have been taken to
      indicate alterations in functional activity. These recent in vivo results
      demonstrate, however, that those changes are, in fact, quantitatively coupled to
      the crux of functional activity, neurotransmitter release. These findings bear
      upon a number of hypotheses concerning the neurophysiological basis of brain
      functional imaging methods.

PMID- 9778569
TI  - Glucose and lactate metabolism in C6 glioma cells: evidence for the preferential
      utilization of lactate for cell oxidative metabolism.
AB  - 13C and 1H nuclear magnetic resonance spectroscopy (NMR) was used to investigate
      the metabolism of L-lactate and D-glucose in C6 glioma cells. The 13C enrichment
      of cell metabolites was examined after a 4-h incubation in media containing 5.5
      mM glucose and 11 mM lactate, each metabolite being alternatively labelled with
      either [1-13C]D-glucose or [3-13C]L-lactate. The results indicated that exogenous
      lactate was the major substrate for oxidative metabolism. They were consistent
      with the concept of the existence of 2 pools of both lactate and pyruvate, of
      which 1 pool was closely connected with exogenous lactate and oxidative
      metabolism, and the other pool was closely related to glycolysis and disconnected
      from oxidative metabolism. The molecular basis of this behaviour could be related
      to different locations for the lactate dehydrogenase isoenzymes, as suggested by
      their immunohistochemical labelling.

PMID- 9778571
TI  - Brain anaerobic lactate production: a suicide note or a survival kit?
AB  - Aerobic energy metabolism utilizes glucose and oxygen to satisfy all the energy
      needs of the adult brain. Anaerobically, the brain switches to the significantly
      less efficient glycolytic pathway for its most basic energy requirements.
      Anaerobic glycolysis provides the adult brain with a limited amount of energy and
      time to maintain ion homoeostasis and other essential processes before several
      events occur that lead to brain cell damage and death. Recent evidence that
      lactate, produced mainly in glial cells during a period of oxygen deprivation,
      becomes the only utilizable and thus obligatory substrate for aerobic energy
      metabolism upon reoxygenation is summarized here. This evidence also supports the
      hypothesis that a lactate shuttle exists between glia and neurons, and emphasizes
      its importance in the post-ischemic survival of neurons.

PMID- 9778570
TI  - Can experimental conditions explain the discrepancy over glutamate stimulation of
      aerobic glycolysis?
AB  - Uncertainty reigns over whether or not glutamate uptake in astrocytes leads to
      strong stimulation of glucose utilization, measured as accumulation of
      radioactive deoxyglucose-6-phosphate. This is an important issue, not only
      because glutamate is the major excitatory transmitter, but also because it has
      been postulated that glutamate-induced stimulation of glycolysis links brain
      excitation with activation of energy production. The effect of glutamate on
      deoxyglucose utilization in cultured rat and mouse astrocytes grown in different
      media and incubated under various conditions during the deoxyglucose assay has,
      therefore, been studied. Under most conditions, no stimulation occurred but
      rather a decrease in deoxyglucose utilization during exposure to glutamate; under
      certain conditions, the contribution of non-metabolized deoxyglucose to the
      intracellular 14C signal was significant.

PMID- 9778572
TI  - Ketone bodies and brain glutamate and GABA metabolism.
AB  - The effects of ketone bodies on brain metabolism of glutamate and GABA were
      studied in three different systems: synaptosomes, cultured astrocytes and the
      whole animal. In synaptosomes the addition of either acetoacetate or 3-OH
      butyrate was associated with diminished consumption of glutamate via
      transamination to aspartate and increased formation of labelled GABA from either
      L-[2H5-2,3,3,4, 4]glutamine or L-[15N]glutamine. There was no effect of ketone
      bodies on synaptosomal GABA transamination. An increase of total forebrain GABA
      and a diminution of aspartate was noted when mice were injected intraperitoneally
      with 3-OH-butyrate. In cultured astrocytes the addition of acetoacetate to the
      medium was associated with a significantly enhanced rate of citrate production
      and with a diminution in the rate of conversion of [15N]glutamate to
      [15N]aspartate. These data are consistent with the hypothesis that the metabolism
      of ketone bodies to acetyl-CoA results in a diminution of the pool of brain
      oxaloacetate, which is consumed in the citrate synthetase reaction (oxaloacetate
      + acetyl-CoA --> citrate). As less oxaloacetate is available to the aspartate
      aminotransferase reaction, thereby lowering the rate of glutamate transamination,
      more glutamate becomes accessible to the glutamate decarboxylase pathway, thereby
      favoring the synthesis of GABA.

PMID- 9778573
TI  - Studies of the source of glucose in the extracellular compartment of the rat
      brain.
AB  - Rats were implanted in the striatum with a glucose biosensor glued to a dialysis
      probe. Changes in extracellular glucose concentration in response to either
      neuronal stimulation or 3-min periods of hypoxia and hyperoxia were compared when
      the dialysis probe was perfused with either artificial cerebrospinal fluid (aCSF)
      alone or aCSF with the addition of the beta-adrenoceptor antagonist propranolol.
      Propranolol had no effect on basal levels of glucose or the changes in glucose
      produced by hypoxia and hyperoxia, which are attributed to changes in the
      utilization of glucose. Following neuronal activation there is an initial
      reduction followed by a delayed, prolonged increase in glucose which is
      suppressed by propranolol. The results suggest that propranolol has no effect on
      glucose utilization, but blocks the delivery of glucose from astrocytes.

PMID- 9778574
TI  - Glucose transporter expression in brain: relationship to cerebral glucose
      utilization.
AB  - Glucose is the principle energy source for mammalian brain. Delivery of glucose
      from the blood to the brain requires its transport across the endothelial cells
      of the blood-brain barrier and across the plasma membranes of neurons and glia,
      which is mediated by the facilitative glucose transporter proteins. The two
      primary glucose transporter isoforms which function in cerebral glucose
      metabolism are GLUT1 and GLUT3. GLUT1 is the primary transporter in the blood
      brain barrier, choroid plexus, ependyma, and glia; GLUT3 is the neuronal glucose
      transporter. The levels of expression of both transporters are regulated in
      concert with metabolic demand and regional rates of cerebral glucose utilization.
      We present several experimental paradigms in which alterations in energetic
      demand and/or substrate supply affect glucose transporter expression. These
      include normal cerebral development in the rat, Alzheimer's disease, neuronal
      differentiation in vitro, and dehydration in the rat.

PMID- 9778575
TI  - Localized in vivo 13C-NMR of glutamate metabolism in the human brain: initial
      results at 4 tesla.
AB  - Using optimized administration of 13C-labeled glucose, the time course of the
      specific activity of glucose was measured directly by in vivo 13C-NMR in the
      human brain at 4 Tesla. Subsequent label incorporation was measured at the C2, C3
      and C4 positions of both glutamate and the well-resolved C2, C3 and C4 resonances
      of glutamine and at the C2 and C3 positions of aspartate. GABA was clearly
      observed for the first time in vivo, suggesting a substantial GABA turnover in
      the normal human visual cortex. Likewise, lactate C3 labeled with an estimated
      active pool size on the order of 0.5 mM. A model of cerebral glutamate metabolism
      is proposed which predicts that glutamatergic action ('neurotransmission'),
      pyruvate carboxylase flux, TCA cycle activity, glucose consumption and exchange
      across the mitochondrial membrane can be assessed simultaneously in the human
      brain.

PMID- 9778577
TI  - Introduction 

PMID- 9778576
TI  - In vitro and ex vivo 13C-NMR spectroscopy studies of pyruvate recycling in brain.
AB  - Pyruvate recycling is a well established pathway in the liver, but in the brain,
      the cellular localization of pyruvate recycling remains controversial and its
      physiological significance is unknown. In cultured cortical astrocytes, pyruvate
      formed from [U-13C]glutamate was shown to re-enter the TCA cycle after conversion
      to acetyl-CoA, as demonstrated by the labelling patterns in aspartate C-2 and C
      3, lactate C-2, and glutamate C-4, which provides evidence for pyruvate recycling
      in astrocytes. This finding is in agreement with previous studies of astrocytic
      cultures, in which pyruvate recycling has been described from [U-13C]glutamine,
      in the presence of glutamate, and from [U-13C]aspartate. Pyruvate recycling in
      brain was studied in fasted rats receiving either an intraperitoneal or a
      subcutaneous injection of [1,2-13C]acetate followed by decapitation 30 min later.
      Extracts of cortical tissue were analysed with 13C-NMR spectroscopy and total
      amounts of amino acids quantified by HPLC. Plasma extracts were analysed with 1H-
      and 13C-NMR spectroscopy, and showed a significantly larger amount of [1, 2
      13C]acetate in the intraperitoneal group compared to the subcutaneous group.
      Furthermore, a small amount of label was detected in glucose in both groups. In
      the subcutaneously injected rats, [4-13C]glutamate and [2-13C]GABA were less
      enriched than plasma glucose, which might have been the precursor. In the
      intraperitoneally injected rats, however, pyruvate formation from [1, 2
      13C]acetate, and re-entry of this pyruvate into the TCA cycle was demonstrated by
      the presence of greater 13C enrichment in [4-13C]glutamate and [4-13C]glutamine
      compared to the subcutaneous group, probably resulting from the significantly
      higher [1, 2-13C]acetate concentration in brain and plasma.

PMID- 9778578
TI  - Glutathione restoration as indicator for cellular metabolism of astroglial cells.
AB  - The restoration of glutathione in astroglia-rich primary cultures derived from
      the brains of newborn rats was used to indicate metabolic properties of
      astroglial cells. At a culture age of 14-21 days these cultures contain an
      average total glutathione content of 32.8 +/- 3.2 nmol/mg protein and a cytosolic
      volume, estimated with the 3-O-methylglucose method, of 4.1 +/- 0.1 microl/mg
      protein. Therefore, cells of astroglial cultures have a cytosolic glutathione
      concentration of about 8 mM. In order to investigate glutathione synthesis in
      astroglial cultures the cellular glutathione content was reduced by starvation in
      a minimal medium lacking glucose and amino acids. Resynthesis of glutathione
      depended on the presence of glucose and the three constituent amino acids
      glutamate, cysteine and glycine. Absence of glucose reduced the amount of net
      glutathione restoration found after 4 h of incubation by about 50%. Of known
      substrates of astroglial energy metabolism, mannose could fully and fructose,
      lactate, pyruvate or sorbitol could partially replace glucose during glutathione
      restoration. In contrast to these compounds, galactose, 5-thioglucose and 2
      deoxyglucose failed to substitute for glucose during glutathione restoration.
      Astroglial cells are able to use as precursors for the three constituent amino
      acids of glutathione a variety of amino acids and dipeptides. The results
      presented demonstrate that glutathione restoration can be used as an indicator
      for amino acid as well as energy metabolism of astroglial cells.

PMID- 9778579
TI  - Metabolic control of kynurenic acid formation in the rat brain.
AB  - Excitotoxic neuronal loss can be precipitated by defects in cerebral energy
      metabolism. Antagonists of excitatory amino acid receptors, such as the
      endogenous metabolite kynurenic acid, can effectively block excitotoxic lesions.
      Using brain tissue slices, the present study was designed to examine a potential
      link between metabolic status and cerebral kynurenic acid formation in adult
      rats. The results demonstrate that fluctuations in cerebral energy metabolism are
      closely associated with changes in kynurenic acid synthesis. Taken together, the
      data are compatible with the idea that the production of kynurenic acid in the
      brain is critically affected by the availability of pyruvate or other 2-oxoacids
      (i.e. co-substrates for the enzymatic transamination of the bioprecursor of
      kynurenic acid, L-kynurenine). Such metabolic control of kynurenic acid function
      may play a role in excitotoxic brain diseases

PMID- 9778580
TI  - Multinuclear NMR spectroscopy studies on NH4Cl-induced metabolic alterations and
      detoxification processes in primary astrocytes and glioma cells.
AB  - Glutamine synthesis, the major pathway of ammonia detoxification, and the
      intracellular concentration of organic osmolytes in primary astrocytes and F98
      glioma cells were investigated with multinuclear magnetic resonance spectroscopy.
      Acute exposure to ammonia (3 h incubation with NH4Cl) raised the concentration of
      glutamine and other amino acids, such as glutamate and aspartate, and decreased
      myo-inositol, hypotaurine, and taurine concentrations. The loss of these
      osmolytes was partially reversed by co-treatment with the glutamine synthetase
      inhibitor, methionine sulphoximine. Glutamate, the precursor of glutamine, is
      provided by stimulated anaplerotic flux via pyruvate carboxylase and glutamate
      dehydrogenase activity. Thus, the glutamine increase and myo-inositol decrease
      observed by in vivo magnetic resonance spectroscopy on patients with hepatic
      encephalopathy may be due to the disturbed osmoregulation in astrocytes caused by
      accumulation of glutamine and the subsequent loss of organic osmolytes.

PMID- 9778581
TI  - In vivo investigation of glutamate-glutamine metabolism in hyperammonemic monkey
      brain using 13C-magnetic resonance spectroscopy.
AB  - To investigate the metabolism of glutamate and glutamine in living monkey brain,
      a system of in vivo 13C magnetic resonance spectroscopy (MRS) using 1H-decoupled
      13C spectroscopy combined with monitoring temperature changes in the brain by MR
      phase mapping was developed. Serial 13C-NMR spectra of the amino acids glutamate
      and glutamine were acquired non-invasively over 4 h from anesthetized monkey
      brain after the intravenous administration of [1-13C]glucose (0.5-1.0 g/kg). In
      the acute hyperammonemic state induced by the administration of ammonium acetate
      (77 mg/kg bolus), it was observed that 13C incorporation into glutamine-4 was
      clearly accelerated, without changes of 13C incorporation into glutamate-4.
      During hyperammonemia, it was shown directly by [2-13C]glucose administration
      that the anaplerotic pathway for the TCA cycle was also augmented, contributing
      to the formation of glutamine in the astroglia.

PMID- 9778582
TI  - 15N-NMR spectroscopy studies of ammonia transport and glutamine synthesis in the
      hyperammonemic rat brain.
AB  - Ammonia transport and glutamine synthesis were studied in the hyperammonaemic rat
      brain in vivo using 15N-NMR spectroscopy at a plasma ammonia level of
      approximately 0.39 mM raised via an intravenous [15N]-ammonium acetate infusion.
      The initial slope of the time course of the summed cerebral 15N-labelled
      metabolites was used to determine the rate of ammonia net transport during
      hyperammonemia as 0.13 +/- 0.02 micromol/min/g (mean +/- SD; n = 5). Based on the
      total accumulation of glutamine and the 1:2 stoichiometric relationship between
      fluxes of four-carbon skeletons and nitrogen atoms, the rate of de novo glutamine
      synthesis through anaplerosis and subsequent glutamate dehydrogenase action was
      calculated to be 0.065 +/- 0.01 micromol/min/g. The rate of total glutamine
      synthesis was estimated to be 0.20 +/- 0.06 micromol/min/g (n = 5) by fitting the
      [5-15N]glutamine time course to a previously described model of glutamate
      glutamine cycling between astrocytes and neurones. A large dilution was also
      observed in [2-15N]glutamine, which supports the glutamate-glutamine cycle as
      being an important pathway for neuronal glutamate repletion in vivo.

PMID- 9778583
TI  - Excitotoxicity and oxidative stress during inhibition of energy metabolism.
AB  - Glutamate receptor involvement and oxidative stress have both been implicated in
      damage to neurons due to impairment of energy metabolism. Using two different
      neuronal in vitro model systems, an ex vivo chick retinal preparation and
      dopamine neurons in mesencephalic culture, the involvement and interaction of
      these events as early occurring contributors to irreversible neuronal damage have
      been examined. Consistent with previous reports, the early acute changes in the
      retinal preparation, as well as irreversible loss of dopamine neurons due to
      inhibition of metabolism, can be prevented by blocking NMDA receptors during the
      time of energy inhibition. Oxidative stress was suggested to be a downstream
      consequence and contributor to neuronal cell loss due to either glutamate
      receptor overstimulation or metabolic inhibition since trapping of free radicals
      with the cyclic nitrone spin-trapping agent MDL 102,832 (1 mM) attenuated acute
      excitotoxicity in the retinal preparation or loss of mesencephalic dopamine
      neurons due to either metabolic inhibition by the succinate dehydrogenase
      inhibitor, malonate, or exposure to excitotoxins. In mesencephalic culture,
      malonate caused an enhanced efflux of both oxidized and reduced glutathione into
      the medium, a significant reduction in total reduced glutathione and a
      significant increase in total oxidized glutathione at time points that preceded
      those necessary to cause toxicity. These findings provide direct evidence for
      early oxidative events occurring following malonate exposure and suggest that the
      glutathione system is important for protecting neurons during inhibition of
      energy metabolism. Consistent with this, lowering of glutathione by buthionine
      sulfoxamine (BSO) pretreatment greatly potentiated malonate toxicity in the
      mesencephalic dopamine population. In contrast, BSO pretreatment did not
      potentiate glutamate toxicity. This latter finding indicates dissimilarities in
      the type of oxidative stress that is generated by the two insults and suggests
      that the oxidative challenge during energy inhibition is not solely a downstream
      consequence of glutamate receptor overstimulation.

PMID- 9778584
TI  - Disturbances of the blood-brain barrier without expression of amyloid precursor
      protein- containing neuritic clusters or neuronal loss during late stages of
      thiamine deficiency in guinea pigs.
AB  - Generalized oxidative deficits associated with experimental thiamine deficiency
      (TD) lead to selective neurodegeneration. In mouse brain, TD produces region
      specific breach of the blood-brain barrier (BBB), neuronal loss and an
      accumulation of amyloid precursor protein (APP) in abnormal neurites. The APP
      laden abnormal neurites within the damaged areas of mouse brain aggregate into
      neuritic clusters which strikingly resemble the neuritic component of Alzheimer
      amyloid plaques. However, amyloid beta-peptide (Abeta) immunoreactivity has not
      been demonstrated in these neuritic clusters, possibly because the Abeta region
      of APP in mice contains three amino acid substitutions as compared with the amino
      acid sequence of human Abeta. In contrast, the guinea pig nucleic acid sequence
      is more related to the human sequence and the Abeta region is identical in
      sequence to that of human APP. Thus, the current studies tested whether the
      presence of an authentic Abeta fragment of APP (i.e., identical to that of man)
      might make guinea pigs more vulnerable to the development of Abeta-containing
      neuritic clusters following TD. During late stages of TD, BBB abnormalities,
      manifested by immunoglobulin G (IgG) extravasation and increased NADPH diaphorase
      reactivity in microvessels, occurred in brain areas known to be damaged by TD in
      mice. However, despite the prolonged thiamine deprivation and the advanced
      neurological symptoms of guinea pigs, no significant neuronal loss or altered
      APP/Abeta immunostaining occurred in any brain region. Microglial activation,
      another early marker of damage in mice, was not evident in thiamine-deficient
      guinea pig brain. Ferritin immunoreactivity and iron deposition in
      oligodendrocytes within areas of BBB abnormalities were either slightly enhanced
      or unchanged as compared to controls. This is the first report of brain
      abnormalities in the guinea pig model of dietary and pyrithiamine-induced TD. The
      results demonstrate species differences in the response to TD-induced damage, and
      further support the role of BBB and nitric oxide in the initial events in TD
      pathology.

PMID- 9778585
TI  - Glyceraldehyde 3-phosphate dehydrogenase abnormality in metabolically stressed
      Huntington disease fibroblasts.
AB  - Huntington disease (HD) fibroblasts subjected to stress exhibit an enzyme profile
      that is different from that exhibited by escapee (unaffected members of families
      with HD) or control fibroblasts. The specific activity of glyceraldehyde 3
      phosphate dehydrogenase (GAPDH) in normally cultured HD fibroblasts was not
      different from that in control and escapee fibroblasts. However, in escapee and
      control fibroblasts subjected to stress by withholding fresh medium, the specific
      activity of GAPDH in cells harvested by trypsinization increased greatly 3 weeks
      after withholding medium ( approximately 8-fold), but the increase was
      significantly less pronounced ( approximately 3-fold) in the HD fibroblasts. In
      contrast, only small changes occurred in the specific activity of lipoamide
      dehydrogenase (LADH) over the same time period, and the values were not
      significantly different among the three groups at any time point. The specific
      activity of hexokinase (HK) was significantly higher in the HD fibroblasts at 1-3
      weeks after withholding fresh medium than in the escapee/control fibroblasts.
      Finally, the total yield of fibroblasts per culture flask (as judged by protein
      content) was significantly greater for the stressed HD fibroblasts than for the
      escapee and control fibroblasts at 2 and 3 weeks after withholding medium. The
      present results are in accord with the hypothesis that HD is a disease associated
      with latent, generalized metabolic abnormalities.

PMID- 9778587
TI  - Evidence for a central cholinergic deficit in congenital ornithine
      transcarbamylase deficiency.
AB  - Congenital ornithine transcarbamylase (OTC) deficiency is the most common inborn
      error of urea cycle enzymes in humans. A large percentage of survivors of
      neonatal OTC deficiency suffer severe developmental disorders, including
      seizures, mental retardation and cerebral palsy. Neuropathological studies reveal
      ventricular enlargement, cerebral atrophy and delayed myelination, as well as
      Alzheimer type II astrocytosis. Using the sparse-fur (spf) mouse model of
      congenital OTC deficiency, studies of central cholinergic integrity revealed a
      developmental delay in choline acetyltransferase activity and of high-affinity
      [3H]-choline uptake in several brain structures. Subsequent studies of muscarinic
      cholinergic binding site distribution showed a widespread loss of M1 sites,
      consistent with cholinergic cell loss. These alterations are similar to those
      reported in Alzheimer's disease, suggesting that the severe cognitive dysfunction
      in congenital OTC deficiency may at least partly result from a muscarinic
      cholinergic lesion. Possible mechanisms involved in the pathogenesis of
      cholinergic cell loss in congenital OTC deficiency include ammonia-induced
      inhibition of pyruvate and alpha-oxoglutarate oxidation, resulting in decreased
      synthesis of acetyl CoA and a cerebral energy deficit, as well as NMDA receptor
      mediated excitotoxicity. Treatment of spf mice with acetyl-L-carnitine (ALCAR)
      results in partial recovery of the developmental choline acetyltransferase
      deficit, suggesting a potential therapeutic benefit of ALCAR in congenital OTC
      deficiency. Other therapies currently used include ammonia-lowering strategies
      (using sodium benzoate or sodium phenylacetate) and, in severe cases, liver
      transplantation.

PMID- 9778586
TI  - Brain ATP metabolism in hypoxia resistant mice fed guanidinopropionic acid.
AB  - Feeding beta-guanidinopropionic acid (GPA), a competitive inhibitor of creatine
      transport, decreases mortality and increases brain ATP stability in hypoxic mice.
      To study brain ATP metabolism in GPA-fed animals, respiratory rates were measured
      in grey matter and white matter slices as well as cerebral hemisphere
      mitochondria from GPA-fed mice and rats. Creatine kinase and adenylate kinase
      activities were measured in rat cerebral grey matter and white matter.
      Respiratory rates and oxidative phosphorylation were the same in GPA-fed mice and
      control mice. The adenylate kinase activity increased 50% and creatine kinase
      showed a small decrease in grey matter. In white matter, creatine kinase
      increased 50% while adenylate kinase decreased. Thus, GPA produces opposite
      adaptive changes in adenylate kinase and creatine kinase in grey matter and in
      white matter. These results suggest that the creatine kinase reaction in grey
      matter acts to regulate cellular ADP and ATP concentrations.

PMID- 9778588
TI  - Putative significance of shifts in acetyl-CoA compartmentalization in nerve
      terminals for disturbances of cholinergic transmission in brain.
AB  - Acetylcholine and acetyl-CoA metabolism in nerve terminals isolated from rat
      brain were found to be affected by several neurotoxic and neuroprotective agents,
      such as aluminium, nitric oxide, beta-hydroxybutyrate, verapamil and thiamine
      deficiency. The changes evoked by these factors in Ca2+-dependent acetylcholine
      release were highly significantly correlated (r = 0.98) with changes in
      concentration of synaptoplasmic acetyl-CoA. On the other hand, in the same
      experimental conditions, no correlation was found between rates of pyruvate
      oxidation, intramitochondrial acetyl-CoA levels and different pools of releasable
      acetylcholine. These data indicate that disturbances in the availability of
      acetyl-CoA in the cytoplasm of nerve terminals may be a key factor in the
      pathogenesis of several cholinergic encephalopathies.

PMID- 9778589
TI  - Synergism of tumor necrosis factor-alpha and melphalan in systemic and regional
      administration: animal study.
AB  - Tumor necrosis factor (TNF) is a highly cytotoxic cytokine. However, due to its
      severe side effects, the only clinical situation allowing its administration in
      humans is isolated limb perfusion (ILP). Early studies have shown that TNF alone
      is of limited efficacy even at high doses via ILP, and that a chemotherapeutic
      agent needs to be added. The most commonly used drug in this setting is melphalan
      which is considered to be synergistic with TNF. However, since melphalan has not
      been commonly used in sarcoma, we believed that confirmation of its synergistic
      effect with TNF in an experimental sarcoma model could prove valuable for future
      drug choice. B16F10 melanoma and CT26 colon carcinoma cells were injected
      subcutaneously (s.c.) into mice, while GF fibrosarcoma cells were injected s.c.
      into the hindleg of Wistar rats. The animals were then divided into four
      treatment groups: TNF alone, melphalan alone, TNF and melphalan, and 0.9% NaCl
      controls. Mice were treated with intraperitoneal injections and rats by ILP. TNF
      dosage was 20 microgram for mice and 200 microgram for rats. Melphalan was given
      at 5-10 mg/kg for both mice and rats. Results showed synergism of TNF and
      melphalan in both modes of therapy. In the systemic administration groups (mice
      carrying B16F10 and CT26 tumors), tumors increased in size in all but the
      combined TNF-melphalan group. In the regional delivery groups (rats carrying GF
      sarcoma cells treated via ILP), there was a 16% decrease in tumor volume in rats
      treated with TNF alone, a 29% decrease in rats treated with melphalan, and a 75%
      decrease in the combined TNF-melphalan group. In conclusion, TNF and melphalan
      proved to be highly synergistic in both systemic and regional delivery. This fact
      makes melphalan an adequate choice for TNF perfusion in advanced limb
      malignancies.

PMID- 9778590
TI  - Effect of bacterial association on the phenotype and genotype of an Entamoeba
      histolytica clonal population.
AB  - A several-times-cloned population of Entamoeba histolytica trophozoites (clone
      MAVIII) was cultured under axenic (MAVIIIax), monoxenic (MAVIIImx) and polyxenic
      (MAVIIIpx) conditions. Clones MAVIIIax and MAVIIImx presented similar virulence
      in vitro, but differed in their virulence in vivo, whereas MAVIIIpx trophozoites
      were neither virulent in vitro or in vivo. The MAVIII clones maintained their
      zymodeme and exhibited three unusual glucose phosphate isomerase bands, absent in
      other E. histolytica strains studied. Similar patterns were shown by the three
      MAVIII clones in the signature of a 482-bp DNA fragment from the M17 gene (which
      encodes for a variable immunodominant antigen), obtained by low stringency single
      specific primer PCR technique. However, MAVIII clones displayed genotypic
      variability in the patterns obtained by the random amplified polymorphic DNA
      technique using total DNA as template. Results suggest that monomorphism is kept
      in certain regions of the genome, mainly in those carrying protein encoding
      genes, but a high polymorphism is present in total DNA of cloned trophozoites
      cultured under different conditions, confirming the plasticity of the E.
      histolytica genome.

PMID- 9778591
TI  - Suppression of adhesion-induced protein tyrosine phosphorylation decreases
      invasive and metastatic potentials of B16-BL6 melanoma cells by protein tyrosine
      kinase inhibitor genistein.
AB  - Protein tyrosine kinase (PTK) appears to be involved in the activation of
      signaling during cell attachment to and spreading on extracellular matrix (ECM)
      in the metastatic cascade. To verify the assumption that PTK inhibitors might
      impair ECM signaling and prevent cancer metastasis, the highly metastatic B16-BL6
      mouse melanoma cells were exposed to the PTK inhibitor genistein for 3 days. The
      ability of the cells to invade through reconstituted basement membrane (Matrigel)
      and to establish experimental pulmonary metastatic foci in C57BL/6 mice decreased
      after genistein exposure. The genistein-treated cells were also prevented from
      attaching to Matrigel and spread extremely poorly on the ECM substratum.
      Immunoblot analysis showed that tyrosine phosphorylation of a 125-kD protein in
      response to cell spreading on Matrigel was suppressed in the genistein-treated
      cells. Adhesion-induced protein tyrosine phosphorylation represents the earlier
      and specific event in the activation of ECM signaling, so this result implied ECM
      signaling was impaired in the treated cells. With immunofluorescence microscopy,
      the adhesion-induced tyrosine phosphorylated proteins were located at the
      pericytoplasms of well-spread cells, but not at the periphery of poorly spread
      genistein-treated cells. Therefore, this paper suggests that genistein might
      impair ECM signaling and subsequently prevent cancer cells from spreading well
      and invading or establishing metastasis through the suppression of adhesion
      induced protein tyrosine phosphorylation. PTKs and adhesion-induced protein
      tyrosine phosphorylation might play a role in the control of invasion and
      metastasis.

PMID- 9778592
TI  - Protein phosphatase-2A associates with the cytoskeleton to maintain cell
      spreading and reduced motility of nonmetastatic Lewis lung carcinoma cells: the
      loss of this regulatory control in metastatic cells.
AB  - Metastatic Lewis lung carcinoma (LLC-LN7) variants have previously been shown to
      have reduced levels of protein phosphatase-2A (PP-2A) activity as compared to the
      nonmetastatic LLC-C8 cells. The present study showed that inhibition of PP-2A in
      the nonmetastatic LLC-C8 cells caused a rapid change from a spread to a rounded
      morphology and increased their in vitro invasiveness through laminin. In
      contrast, the metastatic LLC-LN7 cells were rounded and invasive, which was not
      affected by inhibition of PP-2A. To determine whether these differences could be
      attributed to alterations in PP-2A association with the cytoskeleton, the extent
      of PP-2A colocalization with microtubules was tested. Immunostaining for tubulin
      showed prominent filamentous fibers in nonmetastatic LLC-C8 cells and small foci
      of PP-2A immunostaining along these microtubules. In contrast, the tubulin
      staining was diffuse throughout the metastatic LLC-LN7 cells and there was little
      evidence of association with PP-2A. Western blot analyses showed that this
      reduced level of PP-2A association with microtubules in metastatic LLC-LN7 cells
      was not due to differences in levels of the PP-2A subunits. Instead, it may be
      due to the reduced association of the subunits into the heterotrimeric form of
      the PP-2A holoenzyme. These studies show the importance of PP-2A in maintaining a
      spread morphology and in restricting invasiveness, and a loss of this regulatory
      control in metastatic cells. This loss of PP-2A regulatory control in metastatic
      cells may be due to a reduction in the trimeric form of the PP-2A holoenzyme.

PMID- 9778593
TI  - Endothelial cell response to human head and neck squamous cell carcinomas
      involves downregulation of protein phosphatases-1/2A, cytoskeletal
      depolymerization and increased motility.
AB  - Cancers, such as human head and neck squamous cell carcinomas (HNSCC), have been
      shown to stimulate angiogenesis by their production of endothelial cell
      proliferative and motility-stimulatory factors. The present studies to elucidate
      the intracellular mechanisms that contribute to the motility response of
      endothelial cells to HNSCC-derived factors showed a decline in the organization
      of actin filaments and microtubules. This HNSCC-induced decline in cytoskeletal
      organization coincided with the downregulation of endothelial cell protein
      phosphatase-1 and 2A (PP-1/2A) activities, and could be mimicked by directly
      inhibiting these enzyme activities with okadaic acid. These results show that the
      increased motility of endothelial cells in response to HNSCC-derived angiogenic
      factors involves downregulation of PP-1/2A activities and, consequently, a
      decline in cytoskeletal organization.

PMID- 9778594
TI  - Alcohol and stroke: pathophysiologic mechanisms.
AB  - Epidemiological evidence indicates that recent heavy alcohol consumption
      increases the risk for all major types of stroke, whereas light-to-moderate
      alcohol intake is associated with a decreased risk of ischemic stroke. Although
      heavy drinking elevates blood pressure, there is no firm evidence to indicate
      that alcohol consumption causes the formation of aneurysms, microaneurysms or
      other lesions in human arteries. Alcohol has been reported to precipitate
      vasoconstriction and rupture of small cerebral arteries in experimental animals.
      Alcohol-induced neck trauma has been shown to precipitate traumatic strokes, and
      alcohol-induced cardiac arrhythmias have been observed in patients with embolic
      brain infarction. The effects of alcohol on hemostasis, fibrinolysis and blood
      clotting are variable and could either prevent or promote the occurrence of
      strokes. The antiatherogenic effects of regular light-to-moderate alcohol
      consumption could be mediated by inhibition of low-density lipoprotein oxidation,
      and by elevated estrogen levels.

PMID- 9778595
TI  - Alcohol, coronary heart disease and stroke: an examination of the J-shaped curve.
AB  - The consistent findings of higher risk of coronary heart disease (CHD) and total
      mortality in non-drinkers compared to light to moderate drinking has been
      interpretated as showing that light or moderate drinking is beneficial to health.
      Non-drinkers, both ex-drinkers and lifelong teetotallers, have an increased
      prevalence of conditions likely to increase morbidity and mortality compared with
      occasional or light drinkers. In addition, regular light drinkers tend to have
      characteristics extremely advantageous to health. Whilst there is considerable
      evidence that alcohol intake at some level has a beneficial effect on CHD, the
      degree of protection claimed is almost certainly exaggerated by comparison with
      an inappropriate control group and by the limited adjustment procedures used to
      take into account the differing characteristics of the various alcohol intake
      groups. The benefit of light to moderate drinking for stroke and all-cause
      mortality is less convincing than the benefit for CHD. If occasional drinkers are
      used as a baseline, no benefit is seen for stroke or all-cause mortality in
      regular or light drinkers and all-cause mortality increases progressively from
      levels of 2 drinks a day. Non-drinkers or lifelong abstainers are unsuitable as a
      baseline group in studies of the effects of alcohol on morbidity and mortality.
      The public health message should emphasise the potential harm of heavier drinking
      rather than concentrating on the possible benefits of light drinking.

PMID- 9778596
TI  - Progressive multifocal leukoencephalopathy in the United States, 1979-1994:
      increased mortality associated with HIV infection.
AB  - To examine trends in progressive multifocal leukoencephalopathy (PML) mortality
      in the United States, we analyzed PML death rates and deaths for 1979 through
      1994, using US multiple cause-of-death data. During the 16-year study period
      3,894 PML deaths were reported. The age-adjusted death rate increased more than
      20-fold, from less than 0.2 per million persons before 1984 to 3.3 per million
      persons in 1994. The increase was attributable to infection with human
      immunodeficiency virus (HIV) which was recorded on 2,267 (89.0%) of 2.546 death
      records from 1991 through 1994. PML age-adjusted death rates increased abruptly
      for all males beginning in 1984 and for black females in 1990. Only a small
      increase was observed for white females. In 1994, PML was reported in 2.1% of
      white males who died with HIV-associated disease compared with 1.2% of white
      females and 1.0% of black males and females who died of similar causes. The
      epidemic of PML deaths is increasing in parallel with the AIDS epidemic. The
      increase in HIV-associated PML deaths, first noted among males, has also become
      apparent among females and probably reflects the increasing importance of drug
      use and heterosexual transmission of HIV. The reason for the higher prevalence of
      PML among white males with HIV infection is unknown.

PMID- 9778597
TI  - The epidemiology of Parkinson's disease in an Australian population.
AB  - A prevalence study of Parkinson's disease (PD) was conducted in the rural town of
      Nambour, Australia. There were 5 cases of PD in a study population of 1207,
      yielding a crude prevalence ratio of 414 per 100,000 (95% confidence interval; 53
      775). We performed a separate case-control study involving 224 patients with PD
      and 310 controls from South East Queensland and Central West New South Wales, to
      determine which factors increase the risk for PD in Australia. A positive family
      history of PD was the strongest risk factor for the development of the disease
      (odds ratio = 3.4; p < 0.001). In addition, rural residency was a significant
      risk factor for PD (odds ratio = 1.8, p < 0.001). Hypertension, stroke and well
      water ingestion were inversely correlated with the development of PD. There was
      no significant difference between patients and controls for exposure to
      herbicides and pesticides, head injury, smoking or depression. The high
      prevalence of PD in Nambour may be explained by rural residency. However, the
      most significant risk factor for PD was a positive family hisotry. This
      demonstrates the need for improved understanding of the genetic nature of the
      disease.

PMID- 9778598
TI  - Relationship of neurological function and age in older women. The study of
      osteoporotic fractures.
AB  - The decline of neurological and neuromuscular function with age in older women
      and in subgroups of older women with selected risk factors for poor function is
      described using cross- sectional analyses of data on 8,080 women from the
      multicenter Study of Osteoporotic Fractures. All twelve performance-based tests
      of muscle strength, balance, gait, somatosensory discrimination and reaction time
      declined with increasing age. On a percentage scale, vibration threshold declined
      the most rapidly with age. Participants who were smokers, physically inactive,
      nonconsumers of alcohol, diabetics and more frequent fallers had poorer age
      adjusted performance than those without these attributes. However, with a few
      exceptions, the rate of decline in performance with age for those with and
      without these characteristics did not differ significantly.

PMID- 9778599
TI  - Cellular and molecular actions of lamotrigine: Possible mechanisms of efficacy in
      bipolar disorder.
AB  - Several clinical studies have investigated the use of the anticonvulsant
      lamotrigine (LTG) as a treatment for bipolar affective disorder. Evidence
      suggests that this drug may have a broad spectrum of utility in this illness,
      having both mood-stabilising (antimanic) and acute antidepressant properties.
      This makes this molecule of particular interest in helping to understand the
      underlying disease processes. In this review, we describe the cellular and
      molecular actions of LTG that may contribute to its action in bipolar disorder.
      LTG preferentially inhibits neuronal hyperexcitability and modifies synaptic
      plasticity via use- and voltage-dependent inhibition of neuronal voltage
      activated Na+ channels and possibly high-voltage-activated Ca>cf6>2+>cf1>
      channels. As a consequence, it reduces excessive transmitter release in the
      brain. Indirectly, these effects would be expected to regulate aberrant
      intracellular and intercellular signalling in critical regions of the limbic
      forebrain where hyperactivity may occur in mania, and thus may be directly
      relevant to its mood-stabilising properties. Whether other molecular actions of
      LTG, for example on monoamine disposition, could contribute to its antidepressant
      activity, are less clear at present but warrant further investigation.

PMID- 9778601
TI  - Gabapentin. Antiepileptic mechanism of action.
AB  - Gabapentin is an antiepileptic drug used in the treatment of partial and
      generalized tonic-clonic seizures. Its antiepileptic mechanism of action is not
      known. The transport of gabapentin across membranes and its demonstrated effects
      on voltage-gated ion channels (sodium, calcium), presynaptic mechanisms that can
      enhance GABAergic inhibition, and ligand-gated ion channels (GABA receptors and
      glutamate receptors) are reviewed.

PMID- 9778600
TI  - Modulation of calcium and potassium currents by lamotrigine.
AB  - Actions of the new antiepileptic drug lamotrigine (LTG) were characterized using
      extracellular and whole cell patch clamp recordings from rat CA1 and CA3
      pyramidal cells in vitro. The results suggest that LTG, beside its previously
      described effect on the fast sodium inward current, also modulates - presumably
      voltage-gated - calcium currents and the transient potassium outward current ID.
      These may be effective mechanisms to inhibit pathological excitation in epilepsy
      and may be of potential benefit in treating underlying cellular disturbances in
      bipolar disorder.

PMID- 9778603
TI  - New antiepileptic drugs and psychopathology.
AB  - The literature on the effects of anticonvulsant drugs on behaviour is reviewed,
      with particular attention to the new agents. Positive psychotropic effects, and
      negative influences on behaviour are noted. The latter include depression and
      psychoses. The drugs most involved seem to be those with GABAergic properties,
      and the role of forced normalisation is discussed.

PMID- 9778602
TI  - New antiepileptic drugs in epileptology.
AB  - New antiepileptic drugs have been developed and released for the treatment of
      chronic focal and secondarily generalized epileptic seizures. The anticonvulsant
      efficacy of these drugs (vigabatrin, lamotrigine, gabapentin, felbamate,
      tiagabine, topiramate and oxcarbazepine) does not seem to be superior to that of
      traditional anticonvulsants. The main advantage of these newly developed drugs is
      a different spectrum of possible adverse events (i.e. these drugs usually do not
      induce sedation). Moreover, interactions with traditional anticonvulsants are
      less common, therefore, comedication with these drugs shows an improved
      tolerability. The availability of new antiepileptic drugs enables us to establish
      an individually tailored anticonvulsant strategy for each patient.

PMID- 9778604
TI  - A history of the use of anticonvulsants as mood stabilizers in the last two
      decades of the 20th century.
AB  - Anticonvulsants have moved into an important position as alternatives and
      adjuncts to lithium carbonate in the treatment of bipolar illness. Work with the
      nonhomologous model of kindled seizures helped in the choice of carbamazepine as
      a potential mood stabilizer and in the study of the mechanisms of action of the
      second generation anticonvulsants carbamazepine and valproate, as well as the
      putative third generation psychotropic anticonvulsants lamotrigine and
      gabapentin. Anticonvulsant neuropeptides such as TRH and nonconvulsant approaches
      with repeated transcranial magnetic stimulation (rTMS) also appear promising.

PMID- 9778605
TI  - Kindling: separate vs. shared mechanisms in affective disorders and epilepsy.
AB  - Kindling is discussed in relation to affective illness as a nonhomologous model,
      which shares the feature of increasing illness severity and evolution over time
      following repeated exposures to certain forms of stimulation. This progressive
      aspect of kindling has proven useful in the study of approaches to
      pharmacotherapeutics, mechanisms and characteristics of drug tolerance, and, most
      recently, illness suppression through physiological rather than pharmacological
      strategies. Each of these themes is described and the mechanisms that have been
      uncovered using the kindling model are discussed in relation to how similar
      principles might apply in affective illness or epilepsy. It is hoped that some of
      the lessons from the kindling model will provide useful and novel insights into
      aspects of treatment and mechanisms of psychiatric and neurologic illnesses.

PMID- 9778606
TI  - Differential treatment of bipolar disorder with old and new antiepileptic drugs.
AB  - Although lithium remains the preferred medication for bipolar disorders, new
      investigations suggest that only 60 to 80% of patients have a good response with
      a classical presentation. The antiepileptics carbamazepine and valproate are
      important alternatives. Several studies have shown that lithium, carbamazepine
      and valproate are effective in pure mania. Mixed mania and rapid cycling respond,
      however, well to valproate. One disadvantage of carbamazepine is its enzyme
      inducing property with the consequence of a decrease of plasma levels of other
      psychotropic medications and a worsening of psychopathology. First data indicate
      a good antimanic and antidepressive efficacy of the new antiepileptic drug
      lamotrigine.

PMID- 9778607
TI  - Clinical studies on the use of lamotrigine in bipolar disorder.
AB  - New mood stabilizers that possess efficacy in the depressed phase of bipolar
      disorder are needed. The use of marketed antidepressants puts bipolar patients at
      some increased risk for drug-induced hypomania/mania and rapid cycling. During
      the development of the antiepileptic, lamotrigine, the drug was observed to
      improve mood, alertness, and social interactions in some patients with epilepsy.
      These early observations provided the rationale for investigations into
      lamotrigine's potential efficacy in bipolar disorder. There are now 14 open
      clinical reports involving a total of 207 lamotrigine-treated patients with
      bipolar disorder that suggest this drug possesses a broad spectrum of efficacy in
      the management of the depressed, hypomanic, manic, and mixed phases of bipolar
      disorder. In an attempt to replicate and extend these preliminary open-label
      prospective findings, a series of multicenter, double-blind, placebo-controlled
      studies evaluating the efficacy and dose-response relationships of lamotrigine in
      the various phases of the illness, including both acute and maintenance designs
      in both bipolar I and II disorder, is ongoing.

PMID- 9778608
TI  - Lamotrigine and gabapentin. Alternative in the treatment of bipolar disorder.
AB  - The anticonvulsants carbamazepine and sodium valproate have efficacy in
      hypomania, bipolar depression and in the prophylaxis of bipolar disorder. This
      paper reviews published evidence on the effects of the new anticonvulsants
      gabapentin and lamotrigine in bipolar disorder. The conclusion is that there is
      good evidence from open studies to indicate that randomised double-blind trials
      of these compounds should be carried out. The pharmacology of these
      anticonvulsants is reviewed and putative predictors of good response identified.

PMID- 9778610
TI  - Female genital disorder as adverse symptom of lamotrigine treatment. A
      serotoninergic effect?
AB  - The new anticonvulsant, lamotrigine, is becoming an important tool in the
      treatment of bipolar disorder, including bipolar depression. Its efficacy in
      bipolar depression might be linked to its inhibition of serotonin uptake. We
      present the case of a female schizoaffective patient successfully treated with
      400 mg of lamotrigine developing considerable genital disorder, a side effect
      well known from the treatment with selective serotonin reuptake inhibitors
      (SSRIs). We suggest that female genital disorder induced by high doses of
      lamotrigine is a serotoninergic side effect.

PMID- 9778609
TI  - Renal impairment as a possible side effect of gabapentin. A single case report.
AB  - A bipolar I manic patient was treated successfully by adding gabapentin to
      perazine and clonazepam. Also initially tolerated well, an increase of creatinine
      after several weeks of GP (2000 mg) was observed which was reversible after
      discontinuation of GP. It is suggested that the possibility of renal dysfunction
      should be kept in mind with the usage of gabapentin.

PMID- 9778611
TI  - Acetazolamide in the treatment of acute mania. A case report.
AB  - Several antiepileptic drugs are also being used in affective disorders. There are
      some hints that also the carbonic anhydrase inhibitor acetazolamide might be
      useful in the treatment of bipolar affective disorder. We report a 39-year-old
      male patient with a history of bipolar affective disorder who presented with his
      second manic episode. Acetazolamide was added to a low dose of valproic acid and
      to perazine. A marked decrease of the BRMAS score was achieved. The implications
      of this case are discussed.

PMID- 9778612
TI  - Lamotrigine in the treatment of schizoaffective disorder.
AB  - There is accumulating evidence for the efficacy of lamotrigine in the treatment
      of bipolar disorder, including bipolar depression, both as monotherapy and in
      combination with sodium valproate. We present the cases of 3 female patients
      admitted to our hospital with the diagnosis of schizoaffective disorder who were
      treated with lamotrigine. While dosages up to 200 mg/day, resulting in serum
      concentrations of less than 5 mg/l, were only partially effective, 400 mg/day
      (with serum concentrations >10 mg/l) led to considerable mood stability, with
      complete remission from paranoid symptoms. We suggest that lamotrigine might be
      helpful in the treatment of schizoaffective disorder, probably with serum
      concentrations of more than 5 mg/l.

PMID- 9778613
TI  - Hormonal treatment of breast cancer: new developments.
AB  - Hormonal treatment of breast cancer has been revisited during the last few years.
      New drugs have been introduced and shown to improve patient outcome, both with
      regard to efficacy and side effects. Historical aspects and newer developments
      are presented. New drugs such as second- and third-generation aromatase
      inhibitors and new antiestrogens have recently been introduced in the clinic or
      are in late development. Promising results have been obtained with new endocrine
      agents in third- and fourth-line treatment. Future research directions are given
      and the endocrine treatment of breast cancer is placed in perspective of future
      therapeutic options using 'biological treatment' to influence the regulation of
      cell growth and cell proliferation.

PMID- 9778614
TI  - Dose-dense adjuvant chemotherapy with epirubicin monotherapy in patients with
      operable breast cancer and >/=10 positive axillary lymph nodes. A feasibility
      study.
AB  - Forty-one patients with operable breast cancer and >/=10 positive axillary lymph
      nodes were treated with 6 cycles of dose-dense adjuvant chemotherapy consisting
      of epirubicin (100 mg/m2) every 2 weeks with G-CSF support. A total of 240 cycles
      were administered, all of them at full dose and 19 (8%) with a delay. Thirty
      eight (93%) patients completed the treatment according to the protocol. The
      relative dose intensity of epirubicin was 0.99. Grade 3 toxicities included
      anemia (3%), nausea and vomiting (5%) and alopecia (71%). After a median follow
      up of 40 months, 16 (39%) patients were free of relapse. In conclusion, the
      present study has shown that the administration of dose-dense chemotherapy with
      epirubicin is feasible in the adjuvant setting with minimal toxicity.

PMID- 9778615
TI  - A randomized comparative study of antiemetic prophylaxis with ondansentron in a
      single 32-mg loading dose versus 8 mg every 6 h in patients undergoing cisplatin
      based chemotherapy.
AB  - In several studies a single dose of 32 mg was compared to an ondansentron (OND)
      administration schedule of every 6 h, yielding no differences in overall
      efficacy. The aim of this randomized comparative study was to identify
      differences of these two schedules on an hour-to-hour control of nausea and
      vomiting, during the first 24 h in patients receiving cisplatin (CDDP)-based
      chemotherapy. One hundred ten patients were randomly assigned to two groups (A
      and B); all received combination chemotherapy with CDDP at a dose of 100 mg/m2.
      OND was administered as follows: group A: 8 mg, 30 min before the infusion of
      CDDP, and repeated every 6 h after the first dose (totally 4 doses) in the first
      24 h, and group B: 32 mg before CDDP, as a loading dose and this was the total
      dose for the first 24 h. No overall difference was noticed during the first 24 h,
      as well as the next 3 days from the infusion of CDDP in the intensity of vomits,
      vomits without gastric content (retches), and nausea. In a more detailed
      monitoring of the distribution of emetic episodes during the first 24 h, there
      were important differences between these two antiemetic schedules: for group A an
      increased vomiting with or without gastric content between midnight and 6 p.m.
      was observed, and for group B between 6 p.m. and midnight (vomits with p 0.03,
      and without gastric content p 0.02). Preloading with the total 24-hour dose of
      OND 32 mg exhibits a more potent antiemetic activity during the initial 18 h,
      becoming weaker over the last 5 h of the first day, whereas the every-6-hour
      schedule leaves periods of poor emesis control between dosing intervals.

PMID- 9778616
TI  - Residual disease and presence of human papillomavirus after conization.
AB  - The objective of this study was to evaluate the incidence of residual disease and
      the presence of human papillomavirus (HPV) after conization. Data on 53 patients
      with carcinoma in situ or microinvasive carcinoma who underwent hysterectomy less
      than 2 months after conization were examined. Seven of 53 patients (13%) had
      positive margins. In 4 of these 7 patients (57%), residual disease was found in
      the postconization hysterectomy specimen. Two of 46 patients (4%) with negative
      margins also had residual disease. HPV DNA was detected by PCR in 27 of 53
      conization specimens and in 2 postconization hysterectomy specimens. Of 2
      patients, 1 did not have residual disease. Residual disease could be present even
      with a negative conization margin, and HPV DNA may be found in a histologically
      normal cervix after conization.

PMID- 9778618
TI  - Role of dose intensity in conservative treatment of anal canal carcinoma. Report
      of 35 cases.
AB  - Chemoradiotherapy (CRT) is considered the standard treatment for anal canal
      cancer. However, the optimum schedule of therapy has yet to be defined. This
      study was carried out to evaluate the role of dose intensity (DI) of chemotherapy
      (ChT) and radiotherapy (RT) on the outcome of patients submitted to CRT. Thirty
      five consecutive patients with anal canal carcinoma received a combination of RT
      (median dose 56 Gy) and ChT (two or more cycles of 5-fluorouracil and mitomycin
      C). With a median follow-up of 33 months, 83% of patients are alive without
      evidence of disease and 70% are colostomy-free. Five-year actuarial disease-free
      survival (DFS) is 74%. Univariate and multivariate analysis was performed to
      determine the correlation of DFS with various clinical and therapeutic
      parameters. Our series confirmed the prognostic negative value of a tumor size >4
      cm. An average relative dose-intensity (ARDI) >0.8 was related to a better
      outcome both in univariate and in multivariate analysis; an overall treatment
      time >70 days was related to a worse DFS in univariate analysis, but these data
      were not confirmed by the Cox model. RT dose was not associated with DFS. In
      conclusion, the results of this study seem to suggest an independent prognostic
      role of ChT DI, as measured by ARDI. The results regarding RT DI are
      inconclusive, and remain a matter for further trials.

PMID- 9778619
TI  - Sequential administration of doxorubicin and paclitaxel followed by
      cyclophosphamide, methotrexate and 5-fluorouracil combination (CMF) in women with
      metastatic breast cancer.
AB  - Although the combination of paclitaxel with doxorubicin has yielded high response
      rates in metastatic breast cancer, severe cardiotoxic events have been reported
      in several patients. The rationale for our study was to evaluate the activity of
      paclitaxel/doxorubicin combination in patients with this disease but to avoid
      excessive cardiotoxicity. Therefore, we administered 4 cycles of
      doxorubicin/paclitaxel followed by 6 cycles of standard cyclophosphamide,
      methotrexate and 5-fluorouracil (CMF) regimen. Study medication consisted of
      doxorubicin 60 mg/m2 as a 15-min intravenous infusion followed by paclitaxel 175
      mg/m2 as a 3-hour infusion. CMF regimen consisted of cyclophosphamide 600 mg/m2
      as 1-hour intravenous infusion followed by methotrexate 40 mg/m2 and 5
      fluorouracil 600 mg/m2 bolus injection. The main toxicity of
      doxorubicin/paclitaxel treatment phase was neutropenia (WHO grade 3/4, 58%), but
      we observed only one cardiac adverse event. Toxicities of the CMF treatment phase
      were not significant. Of 24 patients evaluable for response, 2 (8%) had complete
      responses and 11 (46%) achieved partial response. Ten additional patients (42%)
      had stable disease. The median time to progression was 12 months and the median
      overall survival was 18.5 months. The sequential administration of doxorubicin
      and paclitaxel followed by CMF appeared active and well tolerated in patients
      with metastatic breast cancer.

PMID- 9778617
TI  - Endoluminal radiotherapy for rectal tumors.
AB  - The present study was performed to evaluate local tumor control and side effects
      of endoluminal radiotherapy given to patients with rectal tumors. Twelve patients
      with adenocarcinoma and 10 patients with villous/adenovillous adenomas were
      treated with curative intent from 1989 to 1995. The majority of patients were of
      advanced age and in poor medical condition, and had previously been found unable
      to undergo radical surgery or colostomy. Three patients had tumor remains
      following radiotherapy, they successfully received local surgery (n = 2) or an
      iridium implant (n = 1) as second-line treatment. Two patients (adenomas) later
      experienced a local relapse. No serious side effects were observed. We conclude
      that endoluminal radiotherapy is an efficacious option for patients with
      malignant or premalignant tumors in the lower rectum who are in poor medical
      condition.

PMID- 9778620
TI  - Mitomycin C, vinorelbine, carboplatin plus granulocyte-macrophage colony
      stimulating factor for treatment of advanced non-small cell lung carcinoma.
AB  - BACKGROUND: The therapeutic potential of chemotherapy in the treatment of
      recurrent or metastatic non-small cell lung carcinoma (NSCLC) seems modest. Thus,
      the search for novel agents and combination regimens with a superior therapeutic
      index has a high priority. The present combination regimen consisting of
      mitomycin C, vinorelbine, carboplatin and granulocyte-macrophage colony
      stimulating factor (GM-CSF) was chosen because of the known activity of these
      agents in NSCLC and their potential drug synergism without (nonhematologic) cross
      toxicity. To prevent/counteract neutropenia that was assumed to represent the
      dose-limiting toxicity, the hematopoietic growth factor GM-CSF was routinely
      adminstered. The objective of our trial was to determine the antitumor efficacy
      and tolerance of this combination regimen in patients with advanced NSCLC.
      PATIENTS AND METHODS: Forty consecutive patients with nonresectable, measurable
      NSCLC (stage IIIB, 7; stage IV, 33) were treated with an intravenous combination
      chemotherapy regimen consisting of mitomycin C 8 mg/m2 on day 1, vinorelbine 40
      mg/m2 on days 1 and 21, and carboplatin 250 mg/m2 on days 1 and 21; GM-CSF 5
      microg/kg was administered subcutaneously on days 2-8 and 22-28. Treatment cycles
      were repeated every 6 weeks. All patients are evaluable in terms of toxicity and
      response assessment. A total of 123 courses was administered. RESULTS: Objective
      tumor response was notes in 16 patients (40%; 95% confidence interval 24.9
      56.7%), including 3 (7.5%) complete and 13 partial responses. There was no change
      in 12 (31.5%) patients, and 12 had progressive disease. Median duration of
      response was 6 (range 3-15) months, the median time to progression for all
      patients was 6.2 (range 1-17.5) months, and the projected median survival time
      was 8.7 (range 1-23.3) months; the 1-year survival rate was 27.5%.
      Myelosuppression was the most frequently encountered adverse reaction; WHO grade
      3 or 4 granulocytopenia and/or thrombocytopenia occurred in 42.5 and 12.5%,
      respectively. Other toxicities were generally mild to moderate, and always fully
      reversible. CONCLUSION: With a 40% major response rate and disease stabilization
      in one additional third of our patients, this drug combination seems to have
      significant activity against advanced metastatic NSCLC. Due to its subjective
      tolerance and ease of administration, further investigation of this regimen in
      the palliative-intent care setting seems warranted.

PMID- 9778621
TI  - Predictive value of Bcl-2 and Bax protein expression for chemotherapeutic effect
      in gastric cancer. A pilot study.
AB  - We investigated tissue staining for Bcl-2 and Bax proteins, which regulate
      apoptosis, as indicators of chemotherapeutic effect in patients with gastric
      cancer. In 23 patients with gastric carcinoma biopsy specimens were obtained
      endoscopically prior to chemotherapy and stained immunohistochemically with anti
      Bcl-2 and anti-Bax antibodies. Patients then were treated with continuous
      infusion of 5-FU and cisplatin. No correlation was seen between chemotherapeutic
      effect and Bcl-2 or Bax alone. However, among the Bax-positive cases, the
      patients with Bcl-2-positive tumors were significantly more chemoresistant (p =
      0.036) and had worse prognoses (p = 0.008) than Bcl-2-negative cases. Therefore,
      immunohistochemical staining for Bcl-2 protein may predict chemotherapeutic
      efficacy or guide specific therapeutic choices in treating Bax-positive tumors.

PMID- 9778622
TI  - Immunohistochemical study of c-erbB-2 protein in colorectal cancer and the
      correlation with patient survival.
AB  - We related events in immunohistochemical studies on formalin-fixed, paraffin
      embedded preparations of 146 colorectal cancer patients. One hundred (68.5%)
      revealed cytoplasmic staining and only 3 of the 100 showed membranous staining.
      Western blot analysis revealed proteins with molecular masses of 185 and 155 kD
      following immunohistochemical membranous and cytoplasmic staining, but only a 155
      kD protein following cytoplasmic staining. Amplification of the c-erbB-2 gene was
      detected in 2 of 44 cases (4.5%). Cytoplasmic c-erbB-2 overexpression correlated
      with tumor size (p < 0.01), subserosal invasion (p < 0.05), liver metastasis (p <
      0.01) and Dukes' classification. Overall survival rates and survival rates for
      Dukes'B patients were significantly lower in the group with cytoplasmic c-erbB-2
      overexpression than in the group without cytoplasmic c-erbB-2 overexpression.
      Multivariate regression analysis showed cytoplasmic c-erbB-2 overexpression to be
      an independent prognostic factor for colorectal cancer. These results suggest
      that overexpression of cytoplasmic c-erbB-2 protein plays an important role in
      the progression of colorectal cancer and is considered to be an independent
      prognostic indicator of this lesion.

PMID- 9778623
TI  - C-myc and c-fos in human osteosarcoma: prognostic value of mRNA and protein
      expression.
AB  - The c-myc and c-fos proto-oncogenes have several putative functions, including
      regulation of cell growth. In many neoplasms c-myc overexpression has been linked
      to poor prognosis. In order to study the role of c-myc and c-fos expression on
      the tumorigenesis, and the metastatic spread of osteosarcoma, frozen and paraffin
      embedded tissue 38 primary osteosarcoma and 10 lung metastases were analyzed. The
      mRNA analysis was performed by quantitative reverse transcription-polymerase
      chain reaction and in situ hybridization. The protein expression was studied by
      Western blot analysis and immunohistochemistry. C-myc and c-fos were found
      overexpressed in a high percentage of the relapsed tumors and of the metastases,
      and overexpression of both oncogenes in the same tumor was strongly correlated to
      the development of metastases (p < 0.05), as 6 of the 7 primary tumors
      overexpressing both the oncogenes gave metastases. In conclusion, both c-myc and
      c-fos are involved in the growth and spread of osteosarcoma and a synchronous
      overexpression of both oncogenes is highly significant for a metastatic potential
      of a primary tumor.

PMID- 9778624
TI  - Immunohistochemical investigation of thymidylate synthase in cervical cancer.
AB  - We prepared a polyclonal antibody against recombinant human thymidylate synthase
      (TS) to evaluate its use in immunohistochemical analysis. Formalin-fixed,
      paraffin-embedded sections of specimens of cervical tissue were prepared from 35
      patients with cervical cancer. The TS immunoreactivity was studied by employing
      the peroxidase-labeled antibody method with our prepared antibody. At the same
      time, the TS activity was determined with the 5-fluoro-2'-deoxyuridylate (FdUMP)
      TS-binding assay in fresh-frozen specimens of these cervical cancers. We observed
      a positive correlation (r = 0.658) between the degree of TS immunoreactivity and
      the TS activity in the binding assay of 9 patients with grade 4 (strongly
      positive) TS immunoreactivity, while 7 patients (78%) exhibited a TS activity of
      5 pmol/g tissue or greater. Nine patients with a TS immunoreactivity of grade 1
      (negative to weakly positive) showed a TS activity <5 pmol/g tissue. The
      difference between the two groups was statistically significant (p < 0.01). TS
      expression was easily detected by the immunohistochemical technique which will
      allow the assessment of the relationship between TS activity and patient outcome.

PMID- 9778625
TI  - Allelic loss and microsatellite instability in prostate cancers in Japan.
AB  - A series of 25 primary prostate cancers in Japanese were screened for loss of
      heterozygosity and microsatellite instability using twelve microsatellite markers
      containing APC, DCC, TP53, BRCA1, and BRCA2. Frequent loss of heterozygosity was
      observed for D8S201 (48%), LPL (48%), and DCC (26%). In contrast, the incidence
      did not exceed 15% at BRCA1 and BRCA2 loci. Microsatellite instability was
      observed in 28% of stage B, C, and D cancers. These data suggest that
      microsatellite instability and loss of unidentified genes on chromosome 8p may be
      involved in carcinogenesis of the prostate; however, BRCA1 and BRCA2 may not be
      largely involved in the development of prostate cancer in the Japanese
      population.

PMID- 9778626
TI  - Tumor angiogenesis as a prognostic predictor in colorectal carcinoma with special
      reference to mode of metastasis and recurrence.
AB  - Tumor angiogenesis has proved to be a useful prognostic determinant for patients
      with various solid tumors. In this study, we investigated the quantitative
      expression of angiogenesis in colorectal carcinoma to determine how angiogenesis
      correlates with clinicopathologic factors and prognosis. One hundred twenty-seven
      specimens resected from patients with primary colorectal carcinoma were
      investigated immunohistochemically using a polyclonal antibody against factor
      VIII-related antigen, and areas with the highest vascular density at the invasive
      tumor margin were counted at 200 times magnification. The microvessel count,
      defined as angiogenesis density (AD), became significantly higher with increase
      in histologic grade (p = 0.02) and Dukes stage (p = 0.001). AD was also
      significantly higher in patients with lymph node metastasis (p = 0. 005),
      lymphatic invasion (p = 0.042), vascular invasion (p < 0.001), and liver
      metastasis (p = 0.0004) than in those without. In addition, patients with
      synchronous distant hematogenous metastasis in stage D disease showed
      significantly higher AD than patients with nonhematogenous metastasis (p =
      0.006). When 27 cases of disease recurrence after surgical resection with
      curative intent were stratified according to mode of spread, AD in cases with a
      hematogenous pattern of relapse proved to be significantly higher than in cases
      with nonhematogenous spread (p < 0.001). No significant differences were,
      however, found in AD when they were subdivided as to operative nodal status (p =
      0.39 and 0.08 in the node-negative and the node-positive group, respectively).
      Multivariate analysis indicated that AD was an independent prognostic factor (p =
      0.0004) in colorectal carcinoma. Quantitative evaluation of tumor angiogenesis at
      the invasive tumor margin is suggested to be a good prognostic indicator and a
      useful predictor for hematogenous spread and recurrence in patients with
      colorectal carcinoma.

PMID- 9778627
TI  - Overexpression of transforming growth factor-beta1 in scirrhous carcinoma of the
      stomach correlates with decreased survival.
AB  - A retrospective study of 50 patients with scirrhous carcinoma of the stomach who
      had undergone surgery was performed to elucidate whether immunohistochemical
      overexpression of transforming growth factor-beta1 (TGF-beta1) could predict the
      patients' survival. To evaluate the proliferative activity of the tumor, the
      proliferating cell nuclear antigen (PCNA) index was used. Expression of TGF-beta1
      was low in 27 patients and high in 23. Clinicopathological characteristics were
      not significantly different between the two groups with high and low TGF-beta1
      expression. Tumors with higher TGF-beta1 expression had higher PCNA indices (p =
      0.0467, unpaired Student's t test). The 5-year survival rate was 40.4% for the
      low TGF-beta1 group and 28.7% for the high TGF-beta1 group (p = 0.0388, log rank
      test). By multivariate analysis, pT, residual tumor, and TGF-beta1 were the
      independent prognostic factors. These results suggest that immunohistochemical
      expression of TGF-beta1 is one of the useful predictors for estimating the
      patients' survival in scirrhous carcinoma of the stomach particularly of the T3
      and T4 stages.

PMID- 9778628
TI  - Enhancement of interleukin-2-induced lymphokine-activated killer activity by
      interleukin 7 against autologous human renal cell carcinoma.
AB  - Adjuvant immunotherapy with interferons and/or interleukin 2 (IL-2) is widely
      used for advanced kidney cancer. However, the results are not satisfactory so
      far. The purpose of this study is to evaluate the inducible activity of
      lymphokine-activated killer (LAK) cells against autologous human renal cell
      carcinoma. The effect of interleukin 7 (IL-7) on IL-2-induced LAK activity was
      assessed by the autologous assay system which we have established. Peripheral
      blood lymphocytes from patients with renal cell carcinoma were stimulated with IL
      2 and/or IL-7, and tested for antitumor activity against autologous renal cell
      carcinoma. In all 10 cases tested, IL-7 alone induced LAK activity. Moreover, IL
      2-induced LAK activity was augmented by the concomitant addition of IL-7. Flow
      cytometry revealed an increase in IL-2-receptor-positive lymphocytes following
      incubation with IL-7. These results suggest that combination therapy using IL-2
      and IL-7 may be a useful treatment for patients with advanced renal cell
      carcinoma.

PMID- 9778629
TI  - Expression of p53 and vascular endothelial growth factor associated with tumor
      angiogenesis and prognosis in gastric cancer.
AB  - Recently, it has been reported that p53 tumor suppressor gene plays an important
      role in controlling tumor angiogenesis by regulating expression of vascular
      endothelial growth factor (VEGF), which is a well-characterized angiogenic
      inducer. In this study, we investigated these antigens' expression together with
      microvessel density, and investigated their clinical importance. One hundred
      twenty specimens resected from patients with gastric carcinoma were investigated
      using immunohistochemical methods. p53 and VEGF expression was observed in 42 and
      35% tumors, respectively. p53 and VEGF staining status was coincided in 72%
      tumors, and a significant correlation was found between p53 and VEGF status. The
      microvessel density, determined by immunostaining for factor VIII-related
      antigen, was significantly higher in p53-positive or VEGF-positive tumors.
      According to prognosis, patients with p53-positive tumors had significantly worse
      survival than those with p53-negative tumors. There was also a significant worse
      survival in the patients with VEGF-positive tumors than those with VEGF-negative
      tumors. Moreover, the 5-year survival rate was lowest in the patients with p53
      positive and VEGF-positive tumors, while it was highest in the patients with p53
      negative and VEGF-negative tumors. In conclusion, both p53 and VEGF significantly
      correlated with tumor vascularity and prognosis in patients with gastric
      carcinoma.

PMID- 9778630
TI  - Clonal composition of malignant fibrous histiocytoma: analysis by PCR-based assay
      of the human androgen receptor gene (HUMARA).
AB  - Malignant fibrous histiocytoma (MFH), the most common soft-tissue sarcoma,
      consists mainly of two different cell populations: histiocytelike and
      fibroblastlike cells. It has been suggested to contain a large amount of reactive
      histiocytes and fibroblasts hard to distinguish from the tumor cells. In this
      study, the clonality of MFH was determined by analyzing the patterns of X
      chromosome inactivation at the human androgen receptor gene (HUMARA) using DNA
      samples from archival snap-frozen and paraffin-embedded tissues. All the eleven
      informative female heterozygotes without severe inflammation showed the
      monoclonal pattern; 8 storiform-pleomorphic (6 distinct, 2 relative monoclonal
      pattern) and 3 myxoid (3 distinct monoclonal pattern) subtype. Although normal
      tissue DNA, amplifiable by the polymerase chain reaction, valid for the assay was
      not available in these cases, statistically at least 5 cases are monoclonal (p =
      0.037 <0.05), even when markedly skewed lyonization were to primarily exist in
      the normal tissue at the highest rate as ever reported (33%). Experiments using
      the mixture of monoclonal and polyclonal DNA at varying ratios have suggested
      that a distinct monoclonal pattern is obtained only when the monoclonal component
      exceeds 80%. Our study demonstrates that most cells that are present in MFH are
      monoclonal in origin which may be the population of tumor cells.

PMID- 9778631
TI  - An analysis of the temperature effects of fever on the intra-host population
      dynamics of Plasmodium falciparum.
AB  - Observations that growth of Plasmodium falciparum in vitro is inhibited by high
      temperatures have led to hypotheses that malaria fever may influence the parasite
      population dynamics, regulating parasite density and synchronizing parasite
      growth. In order to investigate the fever hypotheses, we have developed an age
      structured coupled Markov chain model that describes the parasite erythrocyte
      cycle and its interaction with the host fever response. We estimated the model
      parameters using data collected from laboratory parasite cultures that were
      exposed to febrile or normal temperature. Using the experimental parameter
      values, quantitative predictions were made of the effect of fever in determining
      the parasite population dynamics. It was concluded from the model behaviour that,
      during the primary infection of a non-immune host, a typical episode of fever can
      effect density-dependent regulation of the parasite population, maintaining
      cycles of parasitaemia and promoting synchronous parasite growth.

PMID- 9778633
TI  - Failure of Schistosoma mansoni to reinfect Biomphalaria glabrata snails: acquired
      humoral resistance or intra-specific larval antagonism?
AB  - Failure of snail reinfection by Schistosoma mansoni has been demonstrated in
      susceptible Biomphalaria glabrata infected with 1 miracidium and subsequently re
      exposed to 1 or 5 homologous parasite larvae. The acquisition of 'resistance' to
      secondary parasite infection was time dependent since complete inhibition was
      observed at 2 weeks and longer following monomiracidial exposure. This phenomenon
      was still observed in snails challenged 8 weeks after primary infection.
      Histological observations revealed that sporocysts from the challenge infection
      were free of encapsulation, their development was stopped and they degenerated
      slowly in the absence of haemocytic reaction of the host. Under the hypothesis of
      an acquired homologous resistance mechanism, this strongly suggests that 1 or
      several unidentified humoral factors are responsible for the non-development of
      the sporocysts from the challenge infection. However, considering the time
      dependent nature of the phenomenon, an intraspecific larval antagonism process
      between sporocysts resulting from the primary infection and those from the
      challenge infection may be involved.

PMID- 9778632
TI  - Modulation of enzymatic activity of Src-family kinases in bovine T cells
      transformed by Theileria parva.
AB  - After infection with sporozoites of the protozoon Theileria parva (Tp) bovine T
      cells are readily transformed to permanent growth in vivo and in vitro. Their
      transformed state depends on the constant presence of the parasite but membrane
      signals remain important. Non-receptor tyrosine kinases play a critical role in
      the transduction of membrane signals in haematopoietic cells. We have
      investigated Src-family kinases in bovine T cells transformed by Tp. The T cell
      receptor-associated tyrosine kinase p60fyn had high activity in all cell lines
      tested. In addition, weak phosphorylation of 2 novel bands was observed
      associated with Fyn. In contrast to Fyn, enzymatic activity of p56lck, which in T
      cells has an essential role in signalling, was low. Furthermore, 1 of 3 Tp
      transformed cell lines was completely devoid of p56lck indicating that the enzyme
      is not necessary for the Tp dependent growth of the T cells. In addition to
      p60fyn and p56lck weak enzymatic activity of 1 splice variant of p53/56lyn was
      observed after infection of T cells with Tp. These data show that growth
      transformation by Tp influences kinase activity in bovine T cells. However, they
      also prove that p56lck does not play an essential role in the transformation
      mechanism.

PMID- 9778634
TI  - The development of schistosomiasis mansoni in an immunologically naive immigrant
      population in Masongaleni, Kenya.
AB  - The relocation of several thousand members of the Kamba tribe from the Kyulu
      Hills to the Thange valley near Masongaleni in Kenya provides an excellent
      opportunity to study the development of the immune response to schistosomiasis
      mansoni in a population with little or no previous experience of the infection.
      An adjacent, well-established Kamba community with similar patterns of water
      contact provides a suitable endemic control population. The immigrants were,
      uniquely, examined shortly after their arrival in the endemic area, while the
      prevalence of infection was still low. At this time faecal egg counts peaked
      atypically around 30 years of age. Over the next 12-18 months infection increased
      rapidly, especially among teenagers, producing a pattern of infection more
      typical of endemic communities. This substantially narrows estimates of the time
      required to develop the important determinants of the age-intensity profile,
      supporting the notion that changes related to age per se, rather than duration of
      infection, dominate. Age-dependent factors might include behaviour or physiology,
      including immune response. This paper provides the background for continuing
      longitudinal studies on the development of immunological responses to this
      parasite.

PMID- 9778635
TI  - Experimental evidence of hybrid breakdown between genetically distinct
      populations of Echinostoma caproni.
AB  - In this paper we investigate whether the assortative mating between individuals
      of the same genetic entity (i.e. coming from the same geographical area) of
      Echinostoma caproni, reported in a previous paper, may be explained by a post
      zygotic isolating mechanism. The fecundity of the adults of 2 parental genetic
      entities and of their hybrids (i.e. F1, F2, F3) was quantified through 3
      successive generations. Whereas the number of eggs released by F1 hybrids is
      similar to that of the mid-parent, that of recombinant hybrids (F2-3 hybrids) is
      significantly lower than that of F1 and that of the mid-parent. Since these
      results seem to demonstrate hybrid breakdown, 2 important factors maintaining
      reproductive isolation, i.e. pre-mating reproductive isolation and low hybrid
      fecundity, may influence the evolution of E. caproni.

PMID- 9778636
TI  - Killing of Gyrodactylus salaris (Platyhelminthes, Monogenea) mediated by host
      complement.
AB  - Gyrodactylus salaris, an important pathogen of Atlantic salmon Salmo salar, has
      been shown to be highly sensitive to factors in host serum and mucus, being
      killed rapidly (50% within 1 h) by serum at a dilution of 1:200. The time needed
      for killing was inversely proportional to serum concentration. Similar effects
      were noted using host mucus, which contained approximately 1/20th of the anti
      Gyrodactylus activity of serum. Serum activity was abolished completely by
      heating at 45 degrees C for 30 min, and by addition of EDTA, but not by EGTA + 1
      mM magnesium ions. Activity was not dependent on whether the serum was from
      infected or naive fishes, nor was it species specific. Attempts to pre-coat
      parasites in salmon anti-Gyrodactylus antibodies also failed to enhance the
      activity of fresh serum. These observations suggest that killing is due to the
      complement system of the host, acting via the alternate pathway. G. salaris
      appears to be exceptionally sensitive to complement, being killed at
      concentrations which could be experienced in vivo. The role of complement in the
      protection of fishes against gyrodactylid infection therefore deserves further
      investigation.

PMID- 9778637
TI  - Spatial and discrimination learning in rodents infected with the nematode
      Strongyloides ratti.
AB  - Recent work has shown that mice with subclinical parasitic infections suffer
      impaired spatial learning and memory, as assayed in an open-field water maze.
      Although the mechanism underlying this effect is not clear, the phenomenon has
      been reported following infection with both a protozoan parasite (Eimeria
      vermiformis) and a gastrointestinal nematode (Heligmosomoides polygyrus). In a
      variety of experiments, we examined the effects of a different gastrointestinal
      nematode, Strongyloides ratti, on the ability of rats and mice to learn a spatial
      or a discrimination task. Animals were tested at various stages post-infection,
      with different levels of infection, using different lines of S. ratti and with
      varying experimental protocols. All animals learned the tasks, but we found no
      evidence of an effect of S. ratti infection on learning or memory. Even rats
      infected with approximately 5000 S. ratti larvae, a dose which has an impact on
      rat body size, showed no deficit in learning ability. Various reasons for the
      conflict between our results and those previously reported for E. vermiformis and
      H. polygyrus are discussed. Our results show that impaired learning and memory
      following parasitic infection is not a ubiquitous or at least easily replicated
      phenomenon.

PMID- 9778639
TI  - The processes influencing the distribution of parasitic nematodes among naturally
      infected lambs.
AB  - The impact of mixed, nematode infection upon a group of animals will depend upon
      the number of nematodes present, how they are distributed among hosts and whether
      individuals that are heavily parasitized with one species are more likely to be
      heavily parasitized with other species. A survey of over 500 six-month-old,
      Scottish Blackface lambs from a single farm in Southwest Strathclyde identified 7
      different categories of nematodes in the abomasum and small intestine. There were
      considerable differences among years and among nematodes in the prevalence and
      mean intensity of infection. Ostertagia circumcincta was present in nearly all
      lambs and judged by prevalence and intensity is one of the most successful of all
      parasitic nematodes. Each category of nematodes had a skewed distribution; most
      animals had relatively few worms but a small proportion had many worms. The
      variance of the number of nematodes in each category were approximately equal to
      the square of the mean. The counts of adult O. circumcincta followed a negative
      binomial distribution, but the negative binomial distribution did not provide a
      good description of the observed values for the other species. These other
      species had a lower prevalence and possibly some sheep were not exposed to
      infection. There was no significant genetic variation among lambs in the number
      of nematodes present and therefore the differences among these lambs were
      unlikely to be a consequence of genetic differences in host susceptibility. Lambs
      with increased numbers of one species were more likely to be have increased
      numbers of the other species, but the correlations were weak and may reflect
      covariation in exposure to different parasites.

PMID- 9778638
TI  - Molecular characterization of a Toxocara variant from cats in Kuala Lumpur,
      Malaysia.
AB  - The ascaridoid nematode of cats from Kuala Lumpur, Malaysia, previously
      identified morphologically as Toxocara canis, was characterized using a molecular
      approach. The nuclear ribosomal DNA (rDNA) region spanning the first internal
      transcribed spacer (ITS-1), the 5.8S gene and the second internal transcribed
      spacer (ITS-2) was amplified and sequenced. The sequences for the parasite from
      Malaysian cats were compared with those for T. canis and T. cati. The sequence
      data showed that this taxon was genetically more similar to T. cati than to T.
      canis in the ITS-1, 5.8S and ITS-2. Differences in the ITS-1 and ITS-2 sequences
      between the taxa (9.4-26.1%) were markedly higher than variation between samples
      within T. canis and T. cati (0-2.9%). The sequence data demonstrate that the
      parasite from Malaysian cats is neither T. canis nor T. cati and indicate that it
      is a distinct species. Based on these data, PCR-linked restriction fragment
      length polymorphism (RFLP) and single-strand conformation polymorphism (SSCP)
      methods were employed for the unequivocal differentiation of the Toxocara variant
      from T. canis and T. cati. These methods should provide valuable tools for
      studying the life-cycle, transmission pattern(s) and zoonotic potential of this
      parasite.

PMID- 9778640
TI  - The detection of Trichinella with polymerase chain reaction (PCR) primers
      constructed using sequences of random amplified polymorphic DNA (RAPD) or
      sequences of complementary DNA encoding excretory-secretory (E-S) glycoproteins.
AB  - Diagnostic PCR primers for Trichinella were constructed. Twelve pairs of primers
      were designed based on the sequences of random amplified polymorphic DNA, and 4
      pairs of primers were designed based on the reported sequences of complementary
      DNA encoding excretory-secretory glycoproteins. With these primers, 31 samples of
      DNA from different strains of Trichinella including 5 species (Trichinella
      spiralis, Trichinella britovi, Trichinella nativa, Trichinella nelsoni and
      Trichinella pseudospiralis) and 3 phenotypes of uncertain taxonomic level
      (Trichinella T5, T6 and T8) were tested with PCR. Genus Trichinella can be
      identified by 4 different primer pairs (SB147D, SB372A, SB153, or Ts43).
      Trichinella spiralis can be identified by the presence of a 673 bp amplicon in
      PCR with the primer pair SB147B. Trichinella nelsoni can be identified using
      primer pair SB147F or by the presence of 673 bp and ca. 380 bp amplicon in PCR
      with the primer pair SB147B. Trichinella pseudospiralis can be identified by 2
      primer pairs (SB147E or SB372B). Trichinella T5 can be identified by the primer
      pair SB147G. Trichinella T8 can be identified by its positivity by the primer
      pair SB147C and its negativity by the primer pair SB372C. A group of Trichinella
      species (T. britovi, T. nativa and Trichinella T6) can be identified by the
      primer pair SB372C.

PMID- 9778641
TI  - Combining data from morphological traits and genetic markers to determine
      transmission cycles in the tape worm, Echinococcus granulosus.
AB  - Species of Echinococcus (Cestoda: Taeniidae) require 2 mammalian hosts to
      complete their life-cycle; a carnivorous definitive host, and a herbivorous or
      omnivorous intermediate host. For most species of Echinococcus, the definitive
      host range is restricted to 1 or a few species, but the intermediate host range
      is very broad. Programmes to control hydatid disease attempt to break the life
      cycle of the parasite and their effectiveness is therefore enhanced by an
      understanding of local patterns of transmission. Although it is known that the
      rostellar hooks of protoscoleces may be influenced by the species of intermediate
      host in which they develop, the application of this knowledge to infer
      transmission cycles has been limited, because the intermediate host effect has
      not been isolated from other environmental and genetic components of phenotypic
      variance. This study presents a method for separating these potentially
      confounding genetic and environmental effects, by combining quantitative genetic
      analyses of hook traits with data on population structure from neutral genetic
      markers. The method was applied to 5 hook traits (hook number, total length of
      large hooks, blade length of large hooks, total length of small hooks, blade
      length of small hooks) measured on protoscoleces from 2 intermediate host types
      (sheep and macropod marsupials) in Australia. Although genetic variance was
      similar for all traits, they differed markedly in the extent of environmental
      variance attributed to development in different host types. Total length of small
      hooks was the trait most affected, with 49-60% of phenotypic variance being
      explained by environmental differences between intermediate host species. Blade
      length of small hooks was least affected, with none of the phenotypic variance
      due to intermediate host origin. These data suggest that hook measurements of
      adult worms from naturally infected definitive hosts could be used to determine
      the intermediate host species from which infection was acquired, if the
      appropriate traits are measured.

PMID- 9778642
TI  - Monitoring of Echinococcus multilocularis infection in red foxes in Shiretoko,
      Japan, by coproantigen detection.
AB  - The study was conducted to evaluate a mAb-based coproantigen detection assay for
      monitoring fox prevalence of Echinococcus multilocularis infections in the
      Shiretoko National Park in Hokkaido, Japan. Eight fox families, each consisting
      of 2-4 adults and their pups, were selected because their territories have been
      determined. Faeces of each family (total n = 537) were collected monthly from
      April to October, 1994. Detection of coproantigen and taeniid eggs was recognized
      in 58 and 27 faeces, respectively, but mostly restricted in 1 family, in which
      coproantigen ELISA OD values had dual peaks, one in June and the other in
      October, whereas taeniid eggs were detected only from April to July. Fox pup
      faeces (n = 51) collected around the dens used by the positive family were all
      coproantigen and taeniid egg negative except for 1 faeces. These results suggest
      that the prevalence and infection pressure in the study area were low and the
      infected family terminated the infection in the summer and acquired a new one in
      the early autumn, 1994. This monitoring method for fox infection will be a
      practical management tool for E. multilocularis infection, especially at the
      tourist spots in Hokkaido where close contact of fox with humans is frequently
      observed.

PMID- 9778643
TI  - GM1 monosialoganglioside pretreatment protects against soman-induced seizure
      related brain damage.
AB  - The effects of GM1 monosialoganglioside pretreatment on brain damage resulting
      from soman-induced seizure activity were examined in this study. Male Sprague
      Dawley rats were infused with GM1 via an osmotic minipump connected through a
      permanent cannula implanted intracerebroventricularly and challenged with soman
      (83 micrograms/kg, i.e., 1.25 x LD50) 4 d after initiation of GM1 infusion.
      Electrocorticographic recordings were monitored via indwelling cortical
      electrodes. Twenty-seven hours after soman administration, anesthetized rats were
      euthanized via transcardial perfusion with buffered paraformaldehyde. Brains were
      processed for hematoxylin and eosin (H&E), cresyl violet (CV), and
      acetylcholinesterase (AChE) histochemistry, and glial fibrillary acidic protein
      (GFAP) and microtubule-associated protein 2 (MAP2) immunohistochemistry. All
      soman-challenged rats not infused with GM1 (n = 14) developed status epilepticus
      (SE).

PMID- 9778644
TI  - Neurovirulent simian immunodeficiency virus induces calbindin-D-28K in
      astrocytes.
AB  - Astrocyte activation has been postulated to be a major contributor to functional
      changes in the brain of AIDS patients. We assessed astrocyte activation in the
      simian immunodeficiency virus (SIV) model. Four groups of macaque brains were
      examined: uninoculated controls, animals inoculated with virus that did not cause
      disease, animals inoculated with virus that caused AIDS but did not cause
      encephalitis, and animals with SIV encephalitis. We examined expression of
      calbindin-D-28K, a calcium binding protein that is upregulated in astrocytes
      during excitotoxic events, as well as glial fibrillary acidic protein (GFAP). The
      presence of calbindin in astrocytes was confirmed by double-labeling using
      confocal microscopy. Increases in calbindin staining were most apparent in the
      white matter, but increases in GFAP staining were most apparent in middle layers
      of the cerebral cortex. Six of the seven animals with SIV encephalitis had
      calbindin immunoreactive astrocytes in the subcortical white matter, corpus
      callosum, internal capsule, cerebral peduncle, pontine white matter, and
      cerebellar white matter. Very rarely, a few, very lightly calbindin
      immunoreactive astrocytes were present in the uninoculated control brains. The
      increase in calbindin expression by astrocytes in SIV encephalitis suggests that
      these cells are subject to calcium toxicity. In uninoculated control macaques,
      and in macaques inoculated with virus that did not cause disease, GFAP
      immunoreactive astrocytes were present throughout the subcortical white matter
      and in layer I, but very few were found in layers III-V of the cerebral cortex.
      Two animals that died of AIDS without encephalitis had somewhat higher numbers of
      GFAP immunoreactive astrocytes in middle cortical layers. In seven animals that
      received passaged neurovirulent virus and developed both AIDS and encephalitis,
      the number of GFAP-immunoreactive astrocytes in middle cortical layers was high,
      indicating widespread astrocyte activation.

PMID- 9778645
TI  - Expression of the antioxidant gene NKEF in the central nervous system.
AB  - Free radicals and the oxidative stress they impose can cause serious injury in
      the nervous system and contribute to pathology associated with a wide variety of
      degenerative and traumatic disorders. In this study, we examined the expression
      of an antioxidant defense gene, nkef, in human tissue and isolated populations of
      rat brain cells using Western and Northern blot analysis. NKEF protein was
      expressed in human brain, liver, kidney, muscle, and lung. The human endothelial
      cell line ECV expressed a 25-kDa band in addition to the 22-kDa band normally
      observed. In the central nervous system, a 22-kDa NKEF band was present in
      cortical gray and white matter, hippocampus, cerebellum, and spinal cord in
      roughly similar amounts. Expression of NKEF-A and NKEF-B subtypes was evaluated
      by Northern analysis of cultured cell types from embryonic rat brain. Astrocyte
      and microglia expressed both 22- and 25-kDa bands, whereas cortical neurons and
      oligodendrocytes contained only the 22-kDa protein band. Northern blot analysis
      of these cell types revealed low levels of NKEF-A message in neurons and
      oligodendrocytes, and relatively low levels of NKEF-B in microglia. Differential
      expression of these antioxidant defense genes may contribute to the selective
      vulnerability of brain cell types to specific kinds of oxidative stress.

PMID- 9778646
TI  - Reversal of impaired oxidative phosphorylation and calcium overloading in the
      skeletal muscle mitochondria of CHF-146 dystrophic hamsters.
AB  - Membrane-mediated excessive intracellular calcium accumulation (EICA) and
      diminished cellular energy production are the hallmarks of dystrophic
      pathobiology in Duchenne and Becker muscular dystrophies. We reported reversal of
      respiratory damage and Ca(2+)-overloading in the in vitro cardiac mitochondria
      from CHF-146 dystrophic hamsters (DH) with hereditary muscular dystrophy
      (Bhattacharya et al., 1993). Here we studied respiratory dysfunctions in the
      skeletal muscle mitochondria from young and old DH, and whether these
      abnormalities can be reversed by reducing [Ca2+] in the isolation medium, thereby
      lowering intramitochondrial Ca(2+)-overloading. Age- and sex-matched CHF-148
      albino normal hamsters (NH) served as controls. As an index of EICA and cellular
      degeneration, Ca and Mg levels were assayed in the skeletal muscle and
      mitochondria. Mitochondria from young and old DH, isolated without EDTA (BE
      medium), revealed poor coupling of oxidative phosphorylation, diminished
      stimulated oxygen consumption rate, and lower respiratory control ratio and ADP/O
      ratios, compared to NH. Incorporation of 10 mM EDTA (Bo medium) in the isolation
      medium restored mitochondrial functions of the dystrophic organelles to a near
      normal level, and reduced Ca(2+)-overloading. The mitochondrial Ca level in DH
      was significantly higher than in NH, irrespective of the medium. However,
      compared to Bo medium, the dystrophic organelles isolated in BE medium had lower
      Ca levels and markedly improved oxidative phosphorylation as seen in NH. Muscle
      Ca contents in the young and old DH were elevated relative to NH, showing a
      positive correlation with the increased mitochondrial Ca(2+)-sequestration.
      Dystrophic muscle also revealed Ca deposition with an abundance of Ca(2+)
      positive and necrotic myofibers by light microscopy, and intramitochondrial
      Ca(2+)-overloading by electron microscopy, respectively. However, Mg levels in
      the muscle and mitochondria did not alter with age or dystrophy. These data
      parallel our observations in the heart, and suggest that functional impairments
      and Ca(2+)-overloading also occur in the skeletal muscle mitochondria of DH, and
      are indeed reversible if EICA is regulated by slow Ca(2+)-channel blocker therapy
      (Johnson and Bhattacharya, 1993).

PMID- 9778647
TI  - Effects of EGb 761 on fatty acid reincorporation during reperfusion following
      ischemia in the brain of the awake gerbil.
AB  - Transient cerebral ischemia (5 min) releases unesterified fatty acids from
      membrane phospholipids, increasing brain concentrations of fatty acids for up to
      1 h following reperfusion. To understand the reported anti-ischemic effect of
      Ginkgo biloba extract (EGb 761), we monitored its effect on brain fatty acid
      reincorporation in a gerbil-stroke model. Both common carotid arteries in awake
      gerbils were occluded for 5 min, followed by 5 min of reperfusion. Animals were
      infused intravenously with labeled arachidonic (AA) or palmitic acid (Pam), and
      rates of incorporation of unlabeled fatty acid from the brian acyl-CoA pool were
      calculated by the model of Robinson et al. (1992), using quantitative
      autoradiography and biochemical analysis of brain acyl-CoA. Animals were treated
      for 14 d with 50 or 150 mg/kg/d EGb 761 or vehicle. Ischemia-reperfusion had no
      effect on the rate of unlabeled Pam incorporation into brain phospholipids from
      palmitoyl-CoA; this rate also was unaffected by EGb 761. In contrast, ischemia
      reperfusion increased the rate of incorporation of unlabeled AA from brain
      arachidonoyl-CoA by a factor of 2.3-3.3 compared with the control rate; this
      factor was further augmented to 3.6-5.0 by pretreatment with EGb 761. There is
      selective reincorporation of AA compared with Pam into brain phospholipids
      following ischemia. EGb 761 further accelerates AA reincorporation, potentially
      reducing neurotoxic effects of prolonged exposure of brain to high concentrations
      of AA and its metabolites.

PMID- 9778648
TI  - The organization of the thalamostriatal projection from the lateral posterior
      thalamic nuclear complex (LP) in the pigmented rat.
AB  - We investigated the thalamostriatal projection of the rat using biotinylated
      dextran amine (BDA) and wheat-germ agglutinin horseradish peroxidase (WGA-HRP).
      To obtain the patch/matrix compartments of the striatum (ST), we used mu-opioid
      receptor (MOR) immunoreaction labeling. Thus, an MOR-positive 'patch' was
      indicated by a darkly stained spot, while the MOR-negative 'matrix' was displayed
      as a non-immunoreactive region. A small injection of BDA was made in a subregion
      of the lateral posterior thalamic nucleus (LP). The LP-ST fibers originated in
      all subregions of LP and terminated in the dorsocaudal portion of ST, where the
      corticostriatal fibers from the visual cortex terminate (Serizawa et al. 1994).
      These LP-ST fibers and terminals were concentrated in the MOR-negative matrix
      compartment. Electron microscopic observations showed that the LP-ST terminals
      made asymmetrical synaptic contacts mainly (70%, n = 30) with the dendritic
      spines of the presumptive ST-output neurons, and fewer (30%) contacted dendritic
      shafts. The present results provide anatomical support for the contention that ST
      output spiny neurons of the matrix that project to the pars reticulata of the
      substantia nigra or globus pallidus, may be influenced directly by the LP-ST
      projection.

PMID- 9778649
TI  - Laminar organization of the intrinsic connection neurons and their axon terminals
      in the lateral suprasylvian cortex of the cat.
AB  - The lateral suprasylvian cortex (LS) of the cat has numerous interconnections
      with other visual cortical areas, as well as with subcortical structures
      implicated in visually-guided behavior. However, little data are available
      regarding connections within the LS itself. In order to investigate the intrinsic
      connections within LS, we have examined the laminar patterns of terminal and
      cellular labeling following injections of either the anterograde tracer biocytin,
      or the retrograde tracer, WGA-HRP, into the subregions of the LS (AMLS, PMLS,
      ALLS, and PLLS). Tracer deposits spanning all cortical layers in a LS subregion
      basically resulted in labeling of axons and terminals (biocytin cases) or cells
      of origin (WGA-HRP cases) in all layers, although intensity of the labeling
      seemed to be different among subregions. The present study demonstrated that the
      interconnections among LS subregions provide no clear evidence of simple
      hierarchial relationships between regions.

PMID- 9778650
TI  - Uneven regional distribution of nucleotide metabolism in human brain.
AB  - Adenine and uridine nucleotides and adenosine are proposed to act as
      neuromodulators and other nucleotides and nucleosides are also suggested to be
      involved in brain function. A following major step towards the verification of
      the functional role of nucleotides and nucleosides in the brain would be the
      examination of regional distribution of purines, pyrimidines and the enzymes
      involved in their metabolism. Using our recently developed chromatography-based
      assay for nucleosides from tissue homogenates, we analysed nucleosides in
      microdissected samples derived from various regions of human brain. Marked
      differences in the levels of nucleosides were measured in the cerebral cortex,
      cerebellar cortex, thalamus and white matter. The greatest levels of most
      nucleosides were found in the cerebral cortex, followed by the cerebellar cortex
      and the white matter while the smallest concentrations were found in the
      thalamus, although adenosine and xanthine showed a different distribution pattern
      in these brain areas. Within the cerebral cortex, the measured substances showed
      little variations except certain high levels in the cingulate and low levels in
      the frontal cortex. Even distribution of nucleosides was found in the thalamic
      nuclei while relative high values were measured in the medial geniculate body.
      Since a dramatic change in nucleoside concentrations occurs after death, the
      measured nucleoside concentrations are an interplay of original nucleotide and
      nucleoside concentrations and enzyme reactions following death. Thus our results
      suggest regional differences in nucleotide and nucleoside composition and
      nucleotide metabolising enzyme activities between brain areas.

PMID- 9778651
TI  - Arachidonic acid modulation of [3H]naloxone specific binding to rat brain opioid
      receptors.
AB  - Arachidonic acid effect on binding of [3H]naloxone to rat brain membranes were
      studied at opioid receptor subtype level. Arachidonic acid inhibited opioid
      receptor binding in a dose-dependent manner, both in the presence and absence of
      sodium. With blockage experiments it was shown that delta-opioid receptors were
      modulated by arachidonic acid to a greater extent than that of mu-opioid
      receptors. On the other hand, there was no significant difference in terms of
      IC50 values for arachidonic acid inhibition of [3H]naloxone binding at agonist
      and antagonist configuration of the receptor subtypes.

PMID- 9778652
TI  - Prolonged noxious stimulation increases periaqueductal gray NMDA mRNA expression:
      a hybridization study using two different rat models for nociception.
AB  - The density and distribution of N-methyl-D-aspartate receptor (NMDAR1) mRNA
      expression in the rat midbrain periaqueductal gray (PAG) following exposure to
      unilateral peripheral inflammation or chronic constrictive injury (CCI) as models
      for chronic peripheral nociception were examined using in situ hybridization
      technique. The NMDAR1 hybridization signal intensities increased significantly in
      the ventrolateral areas of the caudal and middle thirds of the PAG after 3 days
      of Complete Freund's Adjuvant (CFA) injection. Likewise, rats subjected to CCI
      showed significant increase in hybridization signal intensities in comparison to
      sham-operated animals in both the ipsi- and contra-lateral ventrolateral
      quadrants of the caudal and middle thirds of the PAG. In the caudal dorsal raphe,
      the CFA and the CCI treated animals showed a significant increase in signal
      hybridization compared to control and sham-operated groups while the rostral
      dorsal raphe showed no significant changes in either CCI or CFA treated groups.
      In contrast, there was no significant change in signal intensity of NMDAR1 mRNA
      in the dorsal subdivisions of the PAG following either CCI or CFA treatment.
      These results demonstrate significant bilateral increase in NMDAR1 mRNA
      expression in the ventrolateral areas of the caudal and middle thirds of the PAG
      and the caudal one half of the dorsal raphe following chronic nociception. The up
      regulation phenomenon may constitute a reactive mechanism against chronic
      neuropathic pain in the PAG.

PMID- 9778653
TI  - Amyloid beta-peptide and its fragments induce acetylcholine release in in vitro
      basal forebrain tissue slices of rat brain, but do not affect the choline uptake.

PMID- 9778654
TI  - Involvement of dopamine and acetylcholine in the interaction between amygdala and
      nucleus accumbens: chronic microdialysis in rats.

PMID- 9778655
TI  - Amyloid beta-peptide treatment induces a redistribution of acetylcholinesterase
      within the enzyme-containing neurons in in vitro tissue cultures.

PMID- 9778656
TI  - Dermatoglyphic analyses in children with cerebral palsy.
AB  - This study was intended to elucidate the diagnostic values of dermatoglyphic
      features on the 45 cerebral palsy (CP) patients (28 boys and 17 girls). There
      were 50 healthy children in the control group. Dermatoglyphic samples were
      obtained from the both groups by using the paper and ink method and than
      analysed. The types of dermal patterns of fingertips, the counts of total ridges,
      the counts of a-b ridges, the values of atd angles, presence or absence of dermal
      patterns in the hypothenar, thenar/I, II, III, IV interdigital areas, presence of
      absence of the palmar flexion lines, were compared between the children with CP
      and control group. It was found that arch, radial loop, whorl prints have
      increased and ulnar print has decreased in boys investigated which was
      significant statistically (p < 0.001). No difference was found between
      investigation and control groups of girls (p > 0.05). The total ridge counts in
      boys and girls of the investigation group were found significantly decreasing
      according to the control group (p < 0.001). There was an important decrease in
      the counts of a-b ridges of investigation group as compared to controls. It was
      significant in boys (p < 0.01) but not in girls (p > 0.05). The values of atd
      angles of the investigation group have increased in the control group (p < 0.001
      in girls and p < 0.01 in boys). The dermal prints in the hypothenar, thenar/I,
      II, III and IV interdigital areas showed important differences in the
      investigation group when compared with the control group (p < 0.01). No clear
      distinction occurred between the two groups from the viewpoint of palmar flexion
      lines (p > 0.05). In conclusion, remarkable differences in comparison to controls
      were found in the dermatoglyphic features of CP cases. In our opinion, by
      undertaking more studies on the subject and examining a higher number of cases it
      will be possible to obtain useful data in CP cases indicative of etiologically.

PMID- 9778657
TI  - Brain serotonin synthesis rates in rhesus monkeys determined by [11C]alpha-methyl
      L-tryptophan and positron emission tomography compared to CSF 5-hydroxyindole-3
      acetic acid concentrations.
AB  - Twelve male, fasted, anesthetized rhesus monkeys were studied with positron
      emission tomography (PET) and [11C]alpha-methyl-L-tryptophan (alpha MTP) to
      determine serotonin synthesis rates as described by Diksic et al. (1991). It was
      expected that the serotonin synthesis rates determined for the whole brain would
      be correlated with CSF 5-hydroxyindole-3-acetic acid concentrations, a measure of
      central serotonin turnover, because both measures were obtained at steady state.
      However, no significant correlation was found. During data analysis, it was
      noticed that the calculated serotonin synthesis rates were significantly
      correlated to free plasma tryptophan (TP) concentrations (r = 0.88, p < .001).
      From repeat scans conducted in six monkeys, it was determined that day-to-day
      variability in free plasma TP and the percentage of protein binding (average
      percent difference was 48 and 37%, respectively) produced most of the variability
      in the calculated serotonin synthesis rates (50%); repeat K images, obtained from
      the PET data alone, differed by only 11%. Calculated serotonin synthesis rates
      reported for [11C]alpha MTP PET studies of humans (Nishizawa et al. 1997) and
      dogs (Diksic et al. 1991) were also highly correlated to reported differences in
      plasma free TP concentrations. It seems that the [11C]alpha MTP model for the
      computation of serotonin synthesis rates is very dependent on plasma free TP
      concentration and that it may not accurately determine actual serotonin synthesis
      rates.

PMID- 9778658
TI  - Effect of chronic serotonin-2 receptor agonist or antagonist administration on
      serotonin-1A receptor sensitivity.
AB  - We have investigated the effect of 5-HT2 receptor agonist or antagonist
      administration on postsynaptic 5-HT1A receptor sensitivity assessed by two
      behavioral measures, reciprocal forepaw treading or hypothermia induced by acute
      injection of the 5-HT1A receptor agonist 8-OH-DPAT. The effectiveness of these
      drug treatments to downregulate 5-HT2A receptors was confirmed by measuring the
      binding of [3H]-ketanserin in cortical homogenates, because all of these drug
      treatments have been shown to result in the downregulation of 5-HT2A receptor
      sites. Acute or chronic treatment of rats with the 5-HT2 receptor antagonist
      mianserin, or chronic administration of the 5-HT2A receptor antagonist
      ketanserin, did not alter 8-OH-DPAT-induced hypothermia or forepaw treading.
      These data indicate that downregulation of 5-HT2A receptors is not sufficient to
      alter these postsynaptic 5-HT1A receptor-mediated responses. Chronic treatment of
      rats with the 5-HT2 receptor agonist DOI, however, resulted in the attenuation of
      both 5-HT1A receptor-mediated responses measured in separate experimental groups.
      The apparent desensitization of 5-HT1A receptors following chronic DOI treatment
      was not accompanied by a change in either the number or affinity of 5-HT1A
      receptor sites as measured by the binding of [3H]-8-OH-DPAT in hippocampal
      homogenates. Chronic activation of 5-HT2 receptors may be one mechanism by which
      the sensitivity postsynaptic 5-HT1A receptors can be regulated.

PMID- 9778659
TI  - Effect of ergotamine on serotonin-mediated responses in the rodent and human
      brain.
AB  - In the rat dorsal hippocampus and dorsal raphe nucleus, the microiontophoretic
      application of ergotamine and 5-HT suppressed the firing activity of CA3
      pyramidal neurons and 5-HT neurons, an effect antagonized by selective 5-HT1A
      receptor antagonists. Co-application of ergotamine prevented the inhibitory
      action of 5-HT on the firing activity of CA3 pyramidal neurons but not of 5-HT
      neurons, indicating that ergotamine acted as a partial 5-HT1A receptor agonist in
      the dorsal hippocampus and as a full agonist at 5-HT1A autoreceptors. Ergotamine
      decreased, in a concentration-dependent manner, the electrically evoked release
      of [3H]5-HT in preloaded rat and guinea pig hypothalamus slices; this effect was
      prevented by the nonselective 5-HT receptor antagonist methiothepin but not by
      the selective 5-HT1B/1D receptor antagonist GR 127935 or the alpha 2-adrenoceptor
      antagonist idazoxan. Although body temperature in humans remained unchanged
      following inhaled ergotamine, in the rat, subcutaneously injected ergotamine
      produced a hypothermia that was prevented by a pretreatment with the 5-HT1A/1B
      receptor/beta-adrenoceptor antagonist pindolol. Finally in humans, ergotamine did
      not alter prolactin or adrenocorticotropic hormone levels, but increased growth
      hormone level, which was prevented by pindolol. Cortisol level was increased in
      humans by ergotamine, but this enhancement was unaltered by pindolol. In
      conclusion, the present results suggest that ergotamine acted in the rat brain as
      a 5-HT1A receptor agonist and as an agonist of terminal 5-HT autoreceptor of a
      yet undefined subtype. In humans, ergotamine also displayed some 5-HT1A receptor
      activity but, probably because of lack of receptor selectivity, it did not
      present the same profile as other 5-HT1A receptor agonists.

PMID- 9778660
TI  - Behavioral, physiological, and neuroendocrine stress responses and differential
      sensitivity to diazepam in two Wistar rat lines selectively bred for high- and
      low-anxiety-related behavior.
AB  - Two Wistar rat lines, selectively bred for high-anxiety-related behavior (HAB)
      and low-anxiety-related behavior (LAB) in the elevated plus-maze test, were
      tested for the susceptibility of their behavioral characteristics to anxiolytic
      treatment and for their endocrine and physiological reactivity to different
      stressors. Injection of 1 mg/kg diazepam failed to affect line differences in
      coping strategy but resulted in a marked (20-fold) decrease in plus-maze anxiety
      in HAB rats; whereas, the anxiolytic effect was less pronounced in LAB animals.
      Biotelemetrical measurements revealed that HAB and LAB rats do not significantly
      differ in their baseline body temperature, locomotor activity, food and water
      intake, or in stress-induced alterations of the diurnal rhythms in these
      parameters. However, line differences were found in acute changes in body
      temperature and locomotor activity following stress exposure, LAB rats responding
      with a greater, albeit shorter, increase in body temperature and activity than
      HAB animals. Basal ACTH and corticosterone plasma levels as well as pituitary
      reactivity to intravenously administered CRH (40 ng/kg) were similar in both
      lines, although, especially in response to plus-maze exposure, HAB rats tended
      toward higher ACTH secretion than LAB rats. These data confirm that animals with
      high or low basal levels of anxiety may be a promising model for studying the
      mechanisms of action of anxiolytic substances. Nevertheless, the endocrine
      findings support the notion that the reactivity of the hypothalamo-pituitary
      adrenocortical system and anxiety-related behavior can be regulated
      independently.

PMID- 9778661
TI  - Role of the basolateral nucleus of the amygdala in the formation of a phobia.
AB  - Specific phobia is an anxiety disorder that does not respond to benzodiazepines.
      The elevated plus-maze test of anxiety is sensitive to benzodiazepines on trial
      1, but during the first 5-min trial the nature of the anxiety generated changes
      to a specific fear of heights, and, as a result, on trial 2 the rats no longer
      respond to benzodiazepines. However, rats that received reversible bilateral
      lesions of the basolateral amygdala (by lidocaine injection) immediately after
      trial 1 responded with an anxiolytic response to chlordiazepoxide when tested 48
      h later on trial 2. Those that received vehicle injections after trial 1 showed
      the usual lack of response to chlordiazepoxide on trial 2. Thus, the basolateral
      amygdala plays a crucial role in the consolidation of information that leads to
      the formation of a specific phobia and subsequent insensitivity to
      benzodiazepines.

PMID- 9778662
TI  - Clonidine blocks acquisition but not expression of conditioned opiate withdrawal
      in rats.
AB  - Previous studies in rodents have reported that clonidine, an alpha 2-adrenergic
      receptor agonist, attenuated conditioned aversions to naloxone-precipitated
      opiate withdrawal when administered prior to each withdrawal conditioning
      episode. The current study was designed to determine whether clonidine could
      modify the expression of previously established conditioned place aversions and
      conditioned suppression of operant responding. Dose- and time-dependent effects
      of clonidine on activity and suppression of operant responding for food
      identified appropriate treatment parameters for subsequent studies in which rats
      rendered dependent on opiates through implantation of morphine pellets were
      tested for: (1) conditioned place aversion; and (2) conditioned suppression of
      operant responding for food (fixed ratio-15 schedule), in a paradigm wherein rats
      received four pairings of naloxone with a distinct tone and odor stimulus.
      Clonidine dose-dependently blocked the acquisition of both conditioned behaviors
      when administered prior to naloxone on each conditioning trial, but was
      ineffective in blocking the expression of these conditioned withdrawal signs when
      administered prior to the test session.

PMID- 9778663
TI  - Effects of the immunostimulant, levamisole, on opiate withdrawal and levels of
      endogenous opiate alkaloids and monoamine neurotransmitters in rat brain.
AB  - This report present evidence that the immunostimulant drug levamisole, (-)-(S)
      2,3,5,6-tetrahydro-6-phenylimidazo[2,1-b] thiazole monohydrochloride, produced a
      significant elevation of endogeneous morphine and codeine levels in brain regions
      and peripheral organs and attenuated the effects of naltrexone-induced withdrawal
      in morphine-addicted rats. Levamisole also significantly altered the metabolism
      of norepinephrine, dopamine, and serotonin in specific brain regions. These
      results suggest that levamisole's attenuation of opiate withdrawal may be related
      to its ability to increase endogeneous opiate alkaloid levels and/or to alter
      central monoaminergic function. Levamisole does not have significant affinity for
      opiate receptors. These results raise the intriguing possibility that agents such
      as levamisole, which elevate the levels of the endogenous opiate alkaloids, might
      be useful for treating narcotic withdrawal. The mechanism for the
      immunostimulatory properties of agents such as levamisole and muramyl dipeptide
      (MDP) have not been established. We suggest that the ability of MDP and
      levamisole to increase endogenous opiate alkaloids may be related to their
      immunostimulatory properties.

PMID- 9778664
TI  - Chronic olanzapine or sertindole treatment results in reduced oral chewing
      movements in rats compared to haloperidol.
AB  - Chronic haloperidol treatment typically produces late-onset, purposeless oral
      chewing movements in laboratory rats with a prevalence of 40 to 60%. Chronic
      clozapine does not produce these movements. Based on the phenomenologic and
      pharmacologic similarities between these rat chewing movements and human tardive
      dyskinesia (TD), the animal movements are often used as a model of tardive
      dyskinesia (TD). Here we report results of the association of oral chewing
      movements in rats with chronic administration of two new antipsychotic drugs,
      olanzapine and sertindole. Because each of these antipsychotic drugs has a very
      low incidence of acute Parkinsonism in human studies, they are candidates for
      showing a low tardive dyskinesia risk. Neither new drug produced a significant
      incidence of haloperidol-like chewing in rats, nor did movement ratings after
      their chronic administration differ from placebo; whereas, haloperidol produced a
      60% prevalence of purposeless chewing and a prevalence significantly increased
      from placebo. This low rate of oral dyskinesias in rats is consistent with
      several of the preclinical characteristics of the drugs and correlates with their
      low acute motor side effects in clinical trials. We propose, although have not
      yet tested in humans, that these animal results will predict low TD liability of
      these drugs.

PMID- 9778666
TI  - The apolipoprotein E epsilon 4 allele is associated with blunting of ketamine
      induced psychosis in schizophrenia. A preliminary report.
AB  - Interindividual differences in the psychotomimetic response to the N-methyl-d
      aspartate receptor antagonist ketamine are commonly observed. The apolipoprotein
      E (APOE) epsilon 4 allele has been associated with reduced severity of positive
      psychotic symptoms in schizophrenia. In this study, we sought to determine if the
      APOE epsilon 4 allele influences the psychotomimetic response to ketamine in
      schizophrenics. Eighteen patients genotyped at the APOE locus underwent a double
      blind infusion of ketamine and of placebo. Ketamine-induced alterations in the
      brief psychiatric rating scale factors were compared between schizophrenics with
      and without the APOE epsilon 4 allele. APOE epsilon 4+ schizophrenics displayed
      significantly reduced ketamine-induced psychosis, as compared to epsilon 4
      patients. These preliminary data indicate that the psychotomimetic response to
      ketamine may be genetically influenced and may provide additional evidence that
      APOE may modify expression of the positive symptoms in schizophrenia.

PMID- 9778665
TI  - Does ketamine-mediated N-methyl-D-aspartate receptor antagonism cause
      schizophrenia-like oculomotor abnormalities?
AB  - Evidence from histological and pharmacological challenge studies indicates that N
      methyl-D-aspartate (NMDA) receptor hypofunction may play an important role in the
      pathophysiology of schizophrenia. Our goal was to characterize effects of NMDA
      hypofunction further, as related to schizophrenia-associated neuropsychological
      impairment. We administered progressively higher doses of ketamine (target plasma
      concentrations of 50, 100, 150, and 200 ng/ml) to 10 psychiatrically healthy
      young men in a randomized, single-blind, placebo-controlled design and assessed
      oculomotor, cognitive, and symptomatic changes. Mean ketamine plasma
      concentrations approximated target plasma concentrations at each infusion step.
      Verbal recall, recognition memory, verbal fluency, pursuit tracking, visually
      guided saccades, and fixation all deteriorated significantly during ketamine
      infusion; lateral gaze nystagmus explained some, but not all, of the smooth
      pursuit abnormalities. We concluded that ketamine induces changes in recall and
      recognition memory and verbal fluency reminiscent of schizophreniform psychosis.
      During smooth pursuit eye tracking, ketamine induces nystagmus as well as
      abnormalities characteristic of schizophrenia. These findings help delineate the
      similarities and differences between schizophreniform and NMDA-blockade-induced
      cognitive and oculomotor abnormalities.

PMID- 9778667
TI  - Green tobacco sickness.

PMID- 9778669
TI  - Premenstrual syndrome: diagnosis and intervention.
AB  - Premenstrual syndrome (PMS) is a recurrent disorder that occurs in the luteal
      phase of the menstrual cycle. It is characterized by intense physical,
      psychologic, and behavioral changes that interrupt interpersonal relationships
      and disrupt the lives of affected women. Up to 40% of women of childbearing age
      have some form of PMS, and up to 10% have severe signs and symptoms. There are at
      least four types of PMS, each with its own constellation of signs and symptoms.
      Related illnesses or illnesses that need to be ruled out include diabetes
      mellitus, thyroid dysfunction, hypoglycemia, and primary and secondary
      dysmenorrhea. Difficulty in identifying the exact etiology of the disorder is
      documented. Diagnostic issues include confusion over exact signs and symptoms,
      differential diagnoses, pertinent laboratory data, careful history taking, and
      the importance of women recording a menstrual cycle history on a calendar.
      Recommended first-line treatments include a diet low in salt, fat, caffeine, and
      sugar; an aerobic exercise regimen; and stress reduction via changes in
      lifestyle.

PMID- 9778670
TI  - Prevention of child abuse and neglect in the primary care setting.
AB  - The number of cases of child abuse and neglect has risen steadily since reporting
      began in the 1960s. Today, child abuse and neglect is a major cause of injury and
      death in those ages 0 to 5. Studies have identified certain factors that increase
      the risk of maltreatment. The primary care practitioner is in an ideal position
      to assess for the presence of risk factors and to provide primary prevention
      interventions. This article defines child abuse and neglect and reviews its
      epidemiology; the risk factors of child abuse and neglect are also summarized.
      The concept of attachment as a theoretical framework is discussed; its
      significance in the attainment of a positive adjustment to the maternal role
      should drive the clinician's thought process. Suggested interventions are aimed
      at strengthening the parent-child relationship, reducing stress, and providing
      support. A protocol is presented that may be a useful guide for the practitioner.

PMID- 9778668
TI  - Influenza viral infections: presentation, prevention, and treatment.
AB  - Each year, 20,000 to 40,000 people in the United States die of influenza and
      associated complications. Influenza infections account for several billion
      dollars in health care expenditures each year. Two important measures to minimize
      the incidence of influenza infection are vaccination and chemoprophylaxis with
      antiviral agents. Vaccinations must be given annually for two reasons: the
      antigenic changes that influenza strains, particularly influenza A, undergo and
      the diminished antibody response that occurs over time. Specific efforts should
      be targeted to high-risk groups. The adverse effects of the vaccine are generally
      mild, with a sore arm being the most common complaint. Chemoprophylaxis is the
      recommended substitute for vaccination in people with egg allergy. The vaccine is
      effective 70% to 90% of the time in preventing illness in healthy individuals.
      Unfortunately, less than 30% of the targeted population receives the vaccination
      each year. More research must be conducted on ways to improve the organization
      and administration of influenza vaccinations.

PMID- 9778671
TI  - Pathologic gambling.
AB  - Pathologic gambling is recognized and clearly defined by the American Psychiatric
      Association. However, many Americans suffer from an addiction to gambling that is
      undiagnosed and, therefore, untreated. Pathologic gambling, like any other
      addiction, can be devastating. Because of the personality characteristic of the
      pathologic gambler, detecting and diagnosing the problem is difficult. In many
      cases, the symptoms of gambling addiction, although distinct, are not recognized
      until a devastating event occurs. The older adult in particular is at great risk
      for addiction to gambling. Health care providers must be aware of the warning
      signs and symptoms of addiction to gambling and be ready to provide information
      that will assist their clients in addressing it. Unfortunately, few programs
      exist in this country to treat the many people suffering from this addiction.
      With the current movement to legalize gambling and the increasing popularity of
      lotteries in many states, the problem of pathologic gambling is sure to escalate.

PMID- 9778672
TI  - Raloxifene: a new class of anti-estrogens for the prevention of osteoporosis.

PMID- 9778674
TI  - Oncologists need to tell terminal patients the truth.

PMID- 9778673
TI  - National survey reveals widespread public misperceptions about lung cancer.

PMID- 9778675
TI  - Lymphatic mapping in the treatment of breast cancer.
AB  - Developed initially for the treatment of malignant melanoma, lymphatic mapping
      and sentinel lymph node biopsy have recently been introduced into the treatment
      of early breast cancer. In breast cancer patients, harvested sentinel lymph nodes
      are evaluated more thoroughly by detailed pathologic examination using serial
      sectioning, immunohistochemistry, and reverse transcriptase-polymerase chain
      reaction (RT-PCR) techniques. This allows for the detection of smaller tumor
      volumes and leads to more accurate staging. Lymphatic mapping has a 68% to 98%
      success rate in identifying the sentinel lymph node. The false-negative rate
      (defined as a negative sentinel lymph node while a higher node or nodes in the
      axilla are positive) is between 0% and 2%. The morbidity associated with this
      procedure is minimal. We believe that lymphatic mapping and sentinel lymph node
      biopsy will ultimately lead to more conservative treatment of patients with
      breast cancer. This article describes the historical background and technical
      aspects of the procedure. This is followed by updated, prospectively collected
      outcomes data from 466 consecutive breast cancer patients who underwent lymphatic
      mapping at the H. Lee Moffitt Cancer Center, as well as an up-to-date review of
      the literature.

PMID- 9778676
TI  - Abstinence rates achieved with buproprion corrected.

PMID- 9778677
TI  - Aggressive pituitary tumors.
AB  - Although almost all pituitary tumors are benign adenomas, a surprisingly large
      number of these tumors invade tissues outside of the pituitary gland. Such
      invasion, by itself, is not diagnostic of pituitary carcinomas, which are
      exceedingly rare (0.13% of 2,342 pituitary tumors in one series). Several
      different criteria are available to determine whether a tumor is invasive.
      Intraoperative biopsies demonstrate an 85% incidence of microscopic invasion of
      the dura. Evidence of gross invasion at surgery and radiologic evidence of
      invasion on magnetic resonance imaging (MRI) and computed tomographic (CT) scans
      occur at a much lower incidence but may be more predictive of surgical cure.
      Invasive adenomas also have higher proliferation rates than do noninvasive
      adenomas, as shown by immunohistochemical detection of proliferating cell nuclear
      antigen (PCNA), Ki-67, and MIB-1. The expression of p53, increased epidermal
      growth factor receptors, and protein kinase C activity also correlate with
      invasion and aggressive behavior. Clinically significant invasion is more
      frequent with macroadenomas. Macroadenomas of all pituitary tumor subtypes except
      gonadotroph macroadenomas have a greater than 50% incidence of gross invasion.
      Currently, there is no accepted means of predicting an adenoma's clinically
      significant invasiveness and long-term aggressiveness.

PMID- 9778678
TI  - Clinical trials referral resource. Clinical trials in non-Hodgkin's Lymphoma.

PMID- 9778679
TI  - Sunscreens do protect against melanoma, says skin cancer specialist.

PMID- 9778680
TI  - PHS guidelines for the management of health-care worker exposures to HIV--Part 1.

PMID- 9778681
TI  - Combining angiostatin with radiation enhances anticancer effects of each.

PMID- 9778682
TI  - Monoclonal antibody may increase survival rate in patients with colorectal
      cancer.

PMID- 9778683
TI  - Role of laparoscopy in the staging of gastrointestinal cancer.
AB  - Accurate staging plays a primary role in determining the appropriate treatment of
      gastrointestinal malignancies. Recently, laparoscopy has emerged as a staging
      modality that is more sensitive and specific in staging most gastrointestinal
      cancers than preoperative imaging modalities. The addition of laparoscopic
      ultrasonographic techniques has achieved even greater staging accuracy.
      Consequently, patients with disease that is amenable to resection are better
      identified, and others with locally advanced disease are spared unnecessary
      laparotomies. Since laparoscopic techniques may be associated with low morbidity
      and a rapid recovery, palliative procedures are being developed for patients with
      advanced gastrointestinal malignancies. This reviews summarizes the current
      status of laparoscopic staging of gastrointestinal malignancies and compares this
      technique to preoperative imaging modalities. Also discussed are promising
      staging technologies and therapeutic procedures that may soon play an important
      role in the management of gastrointestinal cancer patients.

PMID- 9778684
TI  - Excess thiamine may promote tumor growth.

PMID- 9778685
TI  - Novel tumor-targeting methods show promise.

PMID- 9778686
TI  - Epidemic Kaposi's sarcoma.
AB  - Kaposi's sarcoma (KS) is the most common malignancy associated with human
      immunodeficiency virus-1 (HIV-1) infection and can result in significant
      morbidity. The clinical course of KS is quite variable, although for the majority
      of patients, KS is ultimately a progressive disease requiring systemic therapy.
      For early indolent KS, local therapies may be appropriate and may provide
      significant palliation. For patients with more advanced or rapidly progressive
      disease, systemic therapy is the treatment of choice. Interferon-alfa (Intron A,
      Roferon-A), with or without antiretroviral agents, is particularly useful for
      patients with relatively preserved immune function. For patients with symptomatic
      visceral disease, pulmonary disease, or rapidly progressive cutaneous disease,
      chemotherapy is the treatment of choice. An increasing number of agents are now
      available for the treatment of KS. Pathogenesis-based treatment and/or preventive
      therapies based on the recognized association between KS-associated herpesvirus
      (KSHV) and KS are likely to be available in the near future.

PMID- 9778687
TI  - Phase I clinical data on novel anticancer, antiangiogenesis drug.

PMID- 9778688
TI  - Role of gp55 in restoring the sensitivity of Friend murine erythroleukemia cells
      to erythropoietin by exposure to dimethyl sulfoxide.
AB  - Although Friend murine erythroleukemia (MEL) cells express the erythropoietin
      receptor (EpoR), they are insensitive to erythropoietin (Epo). The
      nonresponsiveness to Epo presumably results from gp55, the product of the env
      gene encoded by the Friend spleen focus-forming virus (F-SFFV), acting as a
      pseudoligand and constitutively activating the receptor. Dimethyl sulfoxide
      (DMSO) induced the differentiation of MEL cells and partially restored
      responsiveness to Epo, with both increased proliferation and further hemoglobin
      synthesis. Treatment of MEL cells with DMSO caused a decrease in the cellular
      content of gp55 as measured by Western analysis and an increase in the level of
      the EpoR as measured by [125I]Epo binding. These changes were produced at least
      in part at the transcriptional level, because DMSO treatment caused a decrease
      and an increase in the levels of the mRNAs for gp55 and EpoR, respectively. To
      ascertain the role of gp55 in the restoration of the sensitivity of MEL cells to
      Epo by exposure to DMSO, expression vectors containing gp55 DNA in the sense and
      antisense orientations were transfected into MEL cells to increase or decrease,
      respectively, the amount of cellular gp55. An increase in the level of gp55
      interfered with the ability of DMSO to restore sensitivity to Epo, whereas a
      decrease in the level of gp55 increased the Epo-sensitizing effects of DMSO.
      [125I]Epo was chemically cross-linked to a component with a calculated molecular
      weight of 65 kDa. DMSO treatment caused an increase in the level of [125I]Epo
      cross-linking. The protein cross-linked to Epo was immunoprecipitated with anti
      EpoR serum but not with anti-gp55 serum, suggesting that Epo was cross-linked to
      its receptor. The finding of a decrease in the cellular content of gp55, an
      increase in the level of the EpoR, and an increase in the formation of the
      Epo/EpoR complex is consistent with the acquisition of sensitivity to Epo by MEL
      cells following treatment with DMSO.

PMID- 9778689
TI  - Activation of the LRP (lung resistance-related protein) gene by short-term
      exposure of human leukemia cells to phorbol ester and cytarabine.
AB  - Treatment-induced secondary drug resistance of tumor cells is a major cause of
      relapsed disease and therapeutic failure in cancer patients. It has been shown
      that the expression of the multidrug resistance MDR1/P-glycoprotein gene could be
      induced by short-term in vitro exposure of cells to protein kinase C (PKC)
      agonists or different chemotherapeutic drugs. We studied whether other genes
      involved in drug resistance are regulated by similar signaling pathways.
      Transient (up to 24 h) treatment of HL-60 or K562 leukemia cells with phorbol 12
      myristate 13-acetate (TPA) resulted in increased steady-state level of LRP (lung
      resistance-related protein) mRNA and protein. Among conventional chemotherapeutic
      drugs tested, only cytarabine (Ara C) induced the LRP mRNA expression though no
      increase in LRP protein was detected. LRP gene activation was not detectable in
      either H9 T-cell leukemia or in solid carcinoma cell lines (BT-20, ZR-75-1, and
      SW 1573). None of the agents influenced the levels of MRP (multidrug resistance
      associated protein) mRNA in any cell line tested. In HL-60 cells, the LRP
      activation by TPA or Ara C was sustained for at least 23 days after withdrawal of
      inducing agents. bis-Indolylmaleimide I, a potent PKC inhibitor, attenuated TPA
      induced LRP activation. In contrast, the inhibitor had no effect on the LRP
      induction by Ara C. These data indicate that the LRP gene can be activated by
      different mechanisms, some of which involve PKC.

PMID- 9778690
TI  - Folylpolyglutamate synthetase expression in antifolate-sensitive and -resistant
      human cell lines.
AB  - Synthesis of poly(gamma-glutamyl) metabolites of many antifolates, such as
      methotrexate (MTX), by folylpolyglutamate synthetase (FPGS) is often essential to
      their cytotoxic activity. FPGS expression in the MTX-sensitive human T
      lymphoblastic leukemia cell line CCRF-CEM and a number of MTX-resistant sublines
      was previously investigated at the DNA, RNA, and activity levels. Using an FPGS
      peptide deduced from its cDNA sequence, a rabbit polyclonal antibody to FPGS has
      now been elicited, immunoaffinity purified, and used to quantitate FPGS protein
      expression by chemiluminescent Western immunoblot analysis. The antibody was used
      to determine the half-life of human FPGS protein (3.7 +/- 1.1 h) in parental CCRF
      CEM cells. A subline resistant to MTX as a result of amplified dihydrofolate
      reductase expression shows no change in FPGS protein or activity relative to CCRF
      CEM. An MTX transport-defective line, however, displays both higher FPGS protein
      and activity levels. For several sublines in which the only apparent mechanism of
      MTX resistance is decreased FPGS activity, the FPGS protein level is decreased
      proportionally. However, we previously showed that these sublines have the same
      gene copy number, restriction map, and mRNA size and levels as the parent.
      Evidently, in these MTX-resistant sublines the mRNA is poorly translated and/or
      the protein turns over more rapidly.

PMID- 9778691
TI  - Anticancer activity of glaucarubinone analogues.
AB  - A series of glaucarubinone analogues, obtained from natural sources as well as
      synthesized by us, were studied both in vitro and in vivo. The focus of the in
      vitro assessment was to define solid tumor-selective compounds by quantitating
      differential cytotoxic activity between murine and human solid tumor cells and
      either murine leukemia or normal cells. Subsequent in vivo studies were aimed at
      determining the therapeutic efficacy of these analogues against the murine
      models. Structure-activity analysis consequent to both the in vitro and in vivo
      studies demonstrated that few changes could be made in the parent glaucarubinone
      structure (outside of the C-15 position) without abrogating either cytotoxicity
      or potency. However, significant changes could be made at the C-15 position which
      modified, either enhanced or diminished, in vitro differential cytotoxicity,
      potency, human solid tumor selectively, and differential cytotoxicity to a MDR
      expressing murine mammary tumor.

PMID- 9778693
TI  - Identification of positive and negative regulator elements for the tissue
      inhibitor of metalloproteinase 1 gene.
AB  - We have identified an IL-10 inducible enhancer (HTE) (5'
      CACGATGACTCATCACTGTTGAAAGACA-3') (-864 to -836 bp) and associated silencer
      element (HTS) (5'-CCACTGGCCCATCGTATAT-3') (-1284 to -1266 bp) in the 5' promoter
      region of the human tissue inhibitor of metalloproteinase-1 (TIMP-1) gene.
      Chloramphenicol acetyl transferase (CAT), electrophoretic migration shift assays
      (EMSAs), and DNase footprinting revealed that IL-10 (15 ng/ml for 1-2 h) induced
      the HTE enhancer. In comparison, phorbol ester stimulated the HTS silencer and
      blocked IL-10's effects in a dose-dependent, orientation- and position
      independent fashion, suggesting that HTS is a true silencer element. EMSAs
      combined with deletion and mutation analysis of the HTE and HTS elements
      confirmed these observations. Finally, Northern blot, Western blot,
      immunoprecipitation, and ELISA analysis showed that IL-10 (15 ng/ml) induced TIMP
      1 expression (approximately 10-fold by 18 h), whereas PMA (100 ng/ml) inhibited
      the stimulatory effects of IL-10 on TIMP-1 expression. The data indicate that HTE
      and HTS function as positive and negative regulatory elements that control human
      TIMP-1 expression.

PMID- 9778692
TI  - Cellular resistance against the novel hybrid anthracycline N-(2-chloroethyl)-N
      nitrosoureidodaunorubicin (AD 312) is mediated by combined altered topoisomerase
      II and O6-methylguanine-DNA methyltransferase activities.
AB  - N-(2-Chloroethyl)-N-nitrosoureidodaunorubicin (AD 312), a novel semisynthetic
      compound with combined anthracycline and nitrosourea alkylating functionalities,
      circumvents resistance conferred by either reduced DNA topoisomerase II (topo II)
      or increased P-glycoprotein expression with less myelosuppression and
      cardiotoxicity than adriamycin (doxorubicin; ADR). Cellular resistance to AD 312
      could arise from a novel mechanism that confers resistance to both functions
      simultaneously, or one or more mechanisms common to anthracyclines and/or
      alkylating agents. The mechanism contributing to AD 312 resistance was
      investigated following selection of AD 312-resistant murine J774.2 macrophage
      like cells and human NCI-H460 non-small-cell lung carcinoma cells. Murine J/312
      400 (> 4.7-fold) and human H/312-40 cells (6.3-fold) were cross-resistant to topo
      II inhibitors (ADR, teniposide, etoposide) and nitrosoureas (carmustine,
      lomustine) but remained sensitive to vinblastine, colchicine, and camptothecin.
      There was approximately a twofold decrease in topo II decatenation activity and
      protein. Decreased net intracellular drug accumulation was not observed. There
      were no increases in glutathione content or glutathione-S-transferase activity.
      Increased O6-methylguanine-DNA methyltransferase (MGMT) activity (2.3-fold) was
      detected in J/312-400, and AD 312 resistance was partially reversed by O6
      benzylguanine, a potent inhibitor of MGMT activity. The results suggest that AD
      312 resistance arose through selective pressure by both cytotoxic functions in a
      serial manner.

PMID- 9778694
TI  - Explaining presbyopia to patients.

PMID- 9778695
TI  - Unilateral Peters' anomaly complicated by a corneal tattoo.
AB  - Anterior segment dysgenesis is characterized by a spectrum of congenital
      anomalies involving the cornea, the iris, and the anterior chamber angle; it may
      be further complicated by systemic anomalies and glaucoma. Peters' anomaly, a
      specific type of mesenchymal anterior segment dysgenesis, is characterized by a
      central corneal leukoma, iridocorneal adhesions, and abnormalities of the
      posterior corneal stroma, Descemet's membrane, corneal endothelium, lens, and
      anterior chamber. Eighty percent of the cases are bilateral. We present an
      unusual unilateral case of Peters' anomaly complicated by postsurgical ocular
      muscle deviation, an iatrogenic corneal tattoo, cataract, and papillary
      conjunctivitis associated with contact lens wear. This article illustrates the
      classification of variants of anterior segment dysgenesis and the technique of
      corneal tatooing, as well as the use of prosthetic contact lenses in the
      management of corneal opacities. We stress that successful management of Peters'
      anomaly requires proper diagnosis of the condition, age-appropriate treatment
      with surgical consultation, and careful follow-up in affected patients.

PMID- 9778696
TI  - Evaluation of mild, moderate, and advanced keratoconus using ultrasound
      pachometry and the EyeSys videokeratoscope.
AB  - BACKGROUND: The absolute accuracy of videokeratoscope (VKS) mapping of
      keratoconus is still in question, with contact lens-induced corneal warpage and
      chalazion having been shown to resemble this condition closely. Corneal thinning
      is investigated as a further aid to the diagnosis and description of keratoconus.
      METHODS: The diagnosis of keratoconus in 41 individuals was verified by measuring
      the corneal thickness difference (I-S difference) between two disparate corneal
      locations, one inferior to (I) and one superior to (S) the corneal apex, using a
      Humphrey model 870 Ultrasound pachometer. Corresponding measures of I-S radii
      were made using radius values obtained from the EyeSys VKS. RESULTS: A comparison
      between I-S pachometry and I-S radius demonstrated a marginally increased
      sensitivity for the latter measurement. Using 95% confidence levels from
      normative pachometric data, classification of severity of keratoconus is proposed
      as follows: (1) keratoconus suspect/early keratoconus: I-S pachometry 75 to 100
      microns; (2) moderate keratoconus: 100 to 125 microns; and (3) advanced
      keratoconus: > 125 microns. CONCLUSION: I-S pachometry can be used as a
      descriptor of keratoconus.

PMID- 9778697
TI  - Evaluation of the EyeSys model II computerized videokeratoscope. Part I: Clinical
      assessment.
AB  - PURPOSE: To compare the agreement and repeatability of keratometry measurements
      with simulated keratometry measurements from the EyeSys (model II) corneal
      analysis system (CAS). Furthermore, to establish any relationship between the
      repeatability of peripheral corneal measurements and the spatial location at the
      cornea. METHODS: Measurements using a Bausch & Lomb keratometer in 19 eyes (19
      subjects) were compared with the simulated keratometry values using the EyeSys
      CAS. Repeatability of the keratometer (14 eyes, 14 subjects) and the EyeSys
      simulated keratometry values (10 eyes, 10 subjects) was assessed by comparing the
      difference of two measurements. Peripheral repeatability of the EyeSys CAS was
      compared in a similar manner in a sample of 10 eyes (10 subjects). RESULTS: The
      95% confidence limits (-0.529 to +0.149 D) showed a lack of agreement between
      both instruments. With respect to the repeatability, both the keratometer (SD =
      +/- 0.103 D) and the EyeSys (SD = +/- 0.072 D) were found to exhibit
      approximately similar degrees of repeatability. The repeatability of peripheral
      corneal measurements using the EyeSys CAS showed changes in repeatability
      dependent on the corneal meridian and the distance from the point of alignment.
      Measurements along the superior and nasal meridians showed poorest repeatability.
      Repeatability was also found to deteriorate away from the point of alignment.
      CONCLUSIONS: EyeSys simulated keratometry values were not interchangeable with
      the keratometer. This could be due to differences in the method of alignment or
      measurements from different areas on the corneal surface. Repeatability of both
      the Bausch & Lomb keratometer and the EyeSys CAS was found to be similar. The
      spatial dependency of peripheral corneal radius repeatability measurements could
      be attributed to interference of the ocular adnexa in those areas of measurement.

PMID- 9778698
TI  - Evaluation of the EyeSys model II computerized videokeratoscope. Part II: The
      repeatability and accuracy in measuring convex aspheric surfaces.
AB  - PURPOSE: To evaluate the precision and repeatability of a Placido disc-based
      computerized videokeratoscope, using convex surfaces of varying eccentricities
      and apical radii designed to simulate the range of topographical variations of
      the human cornea, rather than the purely spherical surfaces used in most previous
      studies. METHODS: Form Talysurf analysis was used to verify the exact form of 12
      Perspex convex surfaces. The EyeSys model II videokeratoscope was used to measure
      the sagittal radii of curvature twice at known points on each surface. The raw
      data tables were analyzed to assess the repeatability and accuracy for both
      central and peripheral points on each surface. The relationship between these
      factors and the eccentricity was investigated. RESULTS: For central radii the
      instrument showed high correlation (r = 0.996) between actual and measured
      values. There was a small instrumental bias of +0.042 mm and the 95% limits of
      agreement were narrow (+0.121 to -0.037 mm), indicating clinically acceptable
      accuracy. The accuracy decreased slightly as the p-value decreased (greater
      peripheral flattening). For peripheral radii, the overall accuracy compared well
      to central radii, with an average bias of +0.022 mm and maximum error in 95% of
      cases 0.083 mm (bias +1.96 x SD). However, for surfaces where p = 0.50, the bias
      was +0.049 and maximum error in 95% of cases 0.110 mm. Repeatability for the
      aspheric surfaces was shown to be high (SD +/- 0.01 mm in all quadrants).
      CONCLUSIONS: The accuracy of the EyeSys corneal analysis system (CAS) in
      measuring central and peripheral radius of curvature was shown to be dependent on
      the shape of the surface to be measured. For more rapidly flattening surfaces, a
      decrease in accuracy was found for both central and peripheral radius of
      curvature, which in clinical terms is thought acceptable.

PMID- 9778699
TI  - Comparison of repeat videokeratography: repeatability and accuracy.
AB  - PURPOSE: We compared the repeatability and accuracy of four commercially
      available videokeratography instruments and a manual keratometer. METHODS: Ten
      optometry students and two university employees who had no history of rigid
      contact lens wear and no soft contact lens wear within 6 months of the study were
      measured. Two independent measurements were taken on the right eyes only using
      the Alcon EyeMap EH-290 topography system (both manual and automatic focus), the
      EyeSys System 2000 corneal topography system, the Humphrey Mastervue topography
      system, the Humphrey Atlas topography system, and a Marco manual keratometer. A
      three-factor repeated measures analysis of variance with all factors repeated was
      performed using SAS and BMDP statistical software. Separate analyses were
      conducted for paracentral and peripheral data. To test accuracy, measurements
      were taken with the Alcon EyeMap automatic focus system, the EyeSys System 2000,
      the Humphrey Atlas system, and the Humphrey Mastervue system using four
      calibration spheres. RESULTS: There were no statistically significant differences
      in the repeatability of the instruments. The EyeSys corneal topography system had
      the most narrow 95% limits of agreement around the mean difference. The two
      Humphrey instruments performed similarly to the EyeSys. Although the Alcon EyeMap
      EH-290 had the widest 95% limits of agreement around the mean difference, it
      showed better repeatability when the manual focus was used compared with the
      automatic focus. The instruments varied in their level of accuracy, but the
      highest percentage of data points within +/- 0.37 D of the known values of the
      calibration spheres was found with the Humphrey Atlas. CONCLUSIONS: Although
      there were no statistically significant differences in repeatability, the EyeSys
      System 2000 had the highest repeatability, which may have clinical relevance. The
      accuracy measured in this study varied tremendously; however, the Humphrey Atlas
      was found to be the most accurate of the instruments tested.

PMID- 9778700
TI  - Signs of surface torsion and torsional dioptric power.
AB  - Although there is agreement in the literature over the magnitude of torsion and
      torsional dioptric power, there is ambiguity over the signs of those quantities.
      The purpose of this paper is to define terms in such a way that the ambiguity is
      removed. Explicit equations are presented for torsion and torsional power along a
      meridian of a surface. In keeping with common practice in other disciplines,
      right-handed torsion is chosen to be positive. The components of the dioptric
      power matrix of thin systems and of the reduced vergence matrix are reinterpreted
      in terms of curvital and torsional power. In this reinterpretation the off
      diagonal components of the matrices remain the torsional power and the reduced
      torsion along the meridian orthogonal to the reference meridian. However, they
      become the negatives of those quantities along the reference meridian. In
      particular, the top-right component can be interpreted as the reduced torsion or
      the torsional power along the meridian orthogonal to the reference meridian and
      the bottom-left as the negative of those quantities along the reference meridian.
      Torsion and torsional power along a meridian, as well as curvature and curvital
      power, are invariant under change of reference meridian and under
      spherocylindrical transposition.

PMID- 9778701
TI  - Vision and attention. II: Is visual attention a mechanism through which a
      deficient magnocellular pathway might cause reading disability?
AB  - Recent research in reading disability has discovered that at least some reading
      disabled subjects have deficits in their magnocellular (M) visual pathways.
      However, the mechanism by which M pathway deficits affect reading has not been
      addressed. Abnormal attention has long been known to be associated with reading
      disabled individuals, and new research in visual attention has determined that
      transient visual attention is dominated by M-stream inputs. The purpose of this
      study was to determine whether visual attention might be the mechanism through
      which a faulty M pathway could produce visual deficits in reading-disabled
      subjects. Spatiotemporal attentional response functions were measured using the
      Line Motion Illusion and compared in normal and disabled readers. Specific
      abnormalities in the visual attention mechanisms of disabled readers were found
      which might suggest mechanisms by which reading could be affected by a deficient
      M stream.

PMID- 9778702
TI  - Assessing the predictive ability of the test-positive findings of an elementary
      school vision screening.
AB  - PURPOSE: The purpose of this study is to assess the predictive ability of the
      test-positive findings of an elementary school vision screening program,
      conducted by 2nd-year optometry students, in identifying children with eye or
      vision disorders. METHODS: A modified version of the Modified Clinical Technique
      (MCT) vision screening was administered to elementary children from a below
      average socioeconomic neighborhood in Houston, Texas. Comprehensive eye and
      vision examinations were provided to the available children who failed the vision
      screening. The screening was administered by groups of 2nd-year optometry
      students with the assistance of a 4th-year optometry student, and supervised by a
      faculty member licensed to practice optometry. The follow-up examinations were
      provided by supervised 4th-year optometry students in a clinical setting based at
      the elementary school. Positive predictive values calculated from the screening
      and examination findings estimate the probability that a failure on one or more
      of the screening tests would identify children with eye or vision disorders.
      RESULTS: Sixty-nine percent of the test-positive children examined were found to
      be true positives by the criteria developed in a study of vision screening
      methods in Orinda, California from 1954 through 1956. CONCLUSIONS: The predictive
      ability of this study's test-positive findings for identifying eye and vision
      disorders was found to be less than the predictive ability of the Orinda Study
      findings. This reduced predictive ability of the present study resulted in a
      larger number of children being overreferred for examinations than had occurred
      in the Orinda Study. The reduction in the ability of the test-positive findings
      of the current study's screening program to identify accurately children with eye
      and vision problems is most likely due to the limited experience of the optometry
      students conducting the screening program. The inability of this retrospective
      study to evaluate the accuracy of the test-negatives is a major limitation in
      assessing the total effectiveness of this vision screening program. Although the
      present study may indicate some value in optometry students conducting elementary
      vision screening programs, a prospective study which could assess the predictive
      ability of both test-positive and test-negative findings, as well as determine
      the sensitivity and specificity of the screening program, is needed to assess
      more fully the effectiveness of school vision screening programs using
      professional students.

PMID- 9778703
TI  - Size and number of epithelial cells washed from the cornea after contact lens
      wear.
AB  - Using the technique of Fullard and Wilson, tear samples were collected
      atraumatically from the corneas of 14 rigid gas permeable (RGP) contact lens
      wearers, 14 soft contact lens (SCL) wearers, and 22 controls who did not wear
      contact lenses. Samples were analyzed for the number, size, and contiguity of the
      cellular contents. Both RGP and SCL groups had, on average, significantly fewer
      cells per sample than controls (median values were 11 and 12 cells vs. 44). The
      difference remained significant even after a correction of three cells was
      applied to account for cells adherent to the lenses. Approximately 80% of
      epithelial cells from both lens wear and control eyes were found in isolation,
      whereas 20% were contiguous with 1 or 2 other cells. This result is compatible
      with the majority of epithelial cells having exfoliated from the surface of the
      cornea after detaching from their neighbors, rather than detaching in sheets of
      cells. The cell length and cell area were analyzed. RGP wearers had significantly
      smaller cells than controls, whereas SCL wearers had slightly (but significantly)
      larger cells. These results may reflect changes in the exfoliation mechanism of
      the corneal epithelium in contact lens wear.

PMID- 9778705
TI  - A pediatrician's view. "What's the big deal? My practice has always been evidence
      based".

PMID- 9778704
TI  - Influence of contact lens material surface characteristics and replacement
      frequency on protein and lipid deposition.
AB  - The aim of the study was to quantify the influence of both contact lens material
      and replacement frequency on protein and lipid deposition. The following
      hypotheses were tested: (1) both protein and lipid interaction with contact
      lenses are material-dependent, and (2) the key factors are the material ionicity
      for the protein deposition and the material chemical composition for the lipid
      deposition. Three high water content contact lens materials were tested:
      netrafilcon A (FDA group II, Gentle Touch), etafilcon A (FDA group IV, Acuvue),
      and vifilcon A (FDA group IV, Focus). Contact lens spoilation was analyzed using
      ultraviolet spectroscopy and fluorescence spectrophotometry. The results showed
      that (1) significantly more proteins were deposited on the ionic materials than
      on the nonionic materials, and that among the ionic materials, the higher the
      ionicity, the higher the level of protein deposition; (2) there were
      significantly more surface proteins on the ionic materials after 3 months than
      after 1 month of wear, but no difference over time was demonstrated for the
      nonionic materials; and (3) significantly more lipids were deposited onto the
      surface of vifilcon A than etafilcon A or netrafilcon A, and the presence of
      vinylpyrrolidone in the vifilcon A formulation was thought to be the cause of
      increased deposition. The protein and lipid interactions with contact lenses were
      found to be material- and time-dependent. Protein attraction was found to be
      related to the material ionicity. The presence of vinylpyrrolidone was a key
      factor in the attraction of lipids.

PMID- 9778707
TI  - Partnership for excellence in asthma care: evidence-based disease management.
AB  - Our experience with developing and implementing the outpatient component of an
      evidence-based disease management initiative has been a positive one. Involvement
      of respected practicing physicians in the planning phase, recommendation of
      evidence-based guidelines, and the supportive relationship between the hospital
      and participating practices have been essential to the successful launching of an
      asthma disease management program by a children's healthcare system. As the
      implementation phase continues to progress, we are preparing for the 6 month data
      collection stage, including outcomes measurement and practice pattern feedback.
      After 1 year of implementation we will analyze the data and report on the effects
      of the Partnership. We expect that physicians will continue to use the
      guidelines, and therefore sustain the improved health status of children with
      asthma. We will continue to invite pediatricians' participation in the
      Partnership so that more children in our community can benefit from high-quality
      cost-effective care that results in superior health outcomes.

PMID- 9778706
TI  - From scientific evidence to child health policy.

PMID- 9778708
TI  - Evidence-based dental care for children and the age 1 dental visit.

PMID- 9778709
TI  - Substantiating the benefits of subspecialty care: pediatric cardiology.

PMID- 9778710
TI  - From appropriate care to evidence-based medicine.

PMID- 9778711
TI  - Hypertonic-hyperoncotic solutions in open-heart surgery.

PMID- 9778712
TI  - Comparison of three plasma expanders used as priming fluids in cardiopulmonary
      bypass patients.
AB  - Ten per cent low molecular weight hydroxyethyl starch is a plasma substitute only
      recently used as priming solution in an extracorporeal circuit, in contrast to
      human albumin and gelatin. To evaluate the effect of priming solutions on
      haemodynamics and colloid osmotic pressure, we studied 36 patients elected for
      cardiopulmonary bypass (CPB). They were randomly assigned to 2.5% hydroxyethyl
      starch, 3% gelatin or 4% human albumin priming solution. Total blood loss
      (perioperative + intensive care unit period) was higher in the gelatin group than
      in the albumin and hydroxyethyl starch groups. During CPB, the colloid osmotic
      pressure was best preserved in the gelatin group, although no excessively low
      colloid osmotic pressures were measured in the other two groups. Due to the
      extended half-life and the additional postoperative colloid administration, the
      hydroxyethyl starch group had a higher colloid osmotic pressure in the
      postoperative phase. We conclude that, next to human albumin, 2.5% hydroxyethyl
      starch is a safe CPB priming solution additive and is effective as plasma
      substitute. Its somewhat longer half-life requires adaptation of the routine
      protocol for transfusion of colloids and blood products.

PMID- 9778713
TI  - Modified ultrafiltration in paediatric cardiopulmonary bypass.
AB  - Cardiopulmonary bypass (CPB), a nonphysiological procedure, is associated with
      haemodilution and the inflammatory response, causing the accumulation of body
      water and organ dysfunction. The purpose of this study was to evaluate the
      efficacy of modified ultrafiltration. Forty paediatric patients undergoing
      cardiac operations were randomized into a control group and a modified
      ultrafiltration group. Blood cells, protein and cytokine concentrations were
      recorded for 24 h postoperatively. As the fluid was removed at 50 ml/min, both
      blood cells and protein were concentrated by modified ultrafiltration (p <
      0.001). The tumour necrosis factor (TNF)-alpha concentration was increased and
      interleukin-8 (IL-8) and endothelin (ET) concentrations were unaltered after
      ultrafiltration. After correction for albumin, TNF-alpha concentration changed
      little, and IL-8 and ET concentrations (36.75 +/- 12.35, 42.89 +/- 15.54) were
      decreased significantly (21.47 +/- 13.87, 26.06 +/- 12.54) after ultrafiltration.
      Modified ultrafiltration is an effective method for removing excess tissue fluid
      and concentrating blood after CPB. This technique can also filter out some
      cytokines.

PMID- 9778714
TI  - A minimal priming technique that allows for a higher circulating hemoglobin on
      cardiopulmonary bypass.
AB  - Reduction in circuit prime during cardiopulmonary bypass has benefits for the
      patient with a low body surface area, anemia, patient refusal to receive blood
      products, and aids the practitioner's goal to minimize exposure to blood
      products. Described here is a simple, low-cost technique that has been shown to
      decrease priming volume in any bypass circuit and allow a significant increase in
      'on bypass hemoglobin'.

PMID- 9778715
TI  - Expression of soluble endothelial adhesion molecules in clinical cardiopulmonary
      bypass.
AB  - Soluble endothelial adhesion molecule expression in clinical cardiopulmonary
      bypass (CPB) was investigated. Neutrophil-mediated endothelial injury plays an
      important role in CPB-induced organ dysfunction. The adhesion of neutrophil to
      the endothelium is central to this process. It has been well documented that CPB
      induces neutrophil activation and changes in neutrophil adhesion molecule
      expression, but the effect of CPB on endothelial cell activation is not known.
      This study was designed to measure soluble endothelial adhesion molecules during
      CPB. We made serial measurements (by specific enzyme-linked immunoabsorbent
      assay) of plasma levels of the soluble endothelial adhesion molecules, ICAM-1 and
      E-selectin in patients undergoing routine CPB (n = 7) and in a control group
      (thoracotomy, n = 3). The results show an initial significant decrease during CPB
      followed by an increase in plasma E-selectin from 29.3 +/- 5.1 ng/ml (mean +/-
      SEM) prebypass to 34.0 +/- 5.4 ng/ml at 48 h postbypass. Likewise, plasma ICAM-1
      significantly decreased during CPB and then increased from 246.3 +/- 38.0 ng/ml
      before bypass to 324.8 +/- 25.0 ng/ml and 355.0 +/- 23.0 ng/ml at 24 and 48 h
      after bypass, respectively. The rise in levels is statistically significant (p <
      0.05). This study shows a decrease in circulating ICAM-1 and soluble E-selectin
      during CPB and an increase in their levels at 48 h after CPB.

PMID- 9778716
TI  - Changes in leucocyte counts and soluble intercellular adhesion molecule-1 and E
      selectin during cardiopulmonary bypass in children.
AB  - A consequence of cardiopulmonary bypass (CPB) in young children is postoperative
      capillary leak and associated pulmonary dysfunction. Neutrophils sequester in the
      lungs and may contribute to functional endothelial damage. The endothelial
      adhesion molecules, E-selectin and intercellular adhesion molecule-1 (ICAM-1),
      mediate sequential steps in adhesion by binding to leucocyte ligands. Circulating
      forms of these proteins have been identified. We studied changes in the plasma
      concentrations of soluble E-selectin and soluble ICAM-1 using fixed phase
      immunoassays, and associated leucocyte counts in 10 paediatric patients
      undergoing CPB. Concentrations of soluble L-selectin and soluble ICAM-1
      consistently fell during CPB from preoperative levels of 89 +/- 17 ng/ml (mean +/
      2SEM) and 218 + 61 ng/ml, respectively, to 39 +/- 7 ng/ml and 84 +/- 24 ng/ml,
      respectively at the beginning of maximum hypothermia. The haemodilution that
      occurred during CPB largely explained this fall, but not the more marked decrease
      in white cell counts that also occurred over this period (6.7 +/- 1.1 to 1.7 +/-
      0.5 x 10(9)/l) which may reflect increased leucocyte sequestration. By 24 h
      postoperatively, levels of both soluble adhesion molecules approached
      preoperative concentrations, as did lymphocyte counts. In marked contrast,
      neutrophil counts rose appreciably towards the end of CPB, and continued to rise
      to a maximum of 10.9 +/- 3.1 x 10(9)/l during the immediate postoperative period
      and remained at these elevated levels 24 h later. Major consistent changes in
      circulating leucocyte numbers which occur early in cardiopulmonary bypass may
      reflect changes in adhesion to the endothelium and consequent sequestration.
      Alterations in the levels of soluble adhesion proteins may influence these
      processes.

PMID- 9778717
TI  - Magnetic resonance spectroscopy of high-energy phosphates and lactate immediately
      after coronary artery bypass surgery.
AB  - Hypothermic cardiopulmonary bypass (CPB) is associated with a high incidence of
      neuropsychological defects, marked cerebral swelling immediately after surgery
      and jugular bulb desaturation during rewarming. This suggests cerebral ischaemia
      may occur, but evidence is indirect. We studied four patients with 31P magnetic
      resonance spectroscopy (MRS) and four with 1H MRS before and immediately after
      coronary surgery. There was no visible lactate in 1H MR spectra. In 31P MR
      spectra, the ratio of phosphocreatine to adenosine triphosphate was maintained
      (before: 2.13 +/- 0.86 vs after: 2.57 +/- 1.31; mean +/- 1 SD) and there was no
      intracellular acidosis (intracellular pH: 7.1 +/- 0.04 vs 7.16 +/- 0.08), while
      phosphocreatine/inorganic phosphate was increased immediately after the operation
      (2.92 +/- 0.37 vs 6.39 +/- 2.67, p = 0.03). This suggests rebound replacement of
      energy stores following recovery from temporary cerebral ischaemia during CPB:
      intra-operative studies would be needed to test this hypothesis further.

PMID- 9778718
TI  - Plasma adrenomedullin level after cardiopulmonary bypass.
AB  - Adrenomedullin is an intrinsic vasodilator which is metabolized mainly in the
      pulmonary circulation. We measured plasma levels of adrenomedullin in children
      with congenital cyanotic heart disease (CY group, n = 6), children with high
      pulmonary blood flow due to congenital heart disease (PH group, n = 8), and in
      adults with mitral valve disease (MV group, n = 7) before and 3 h after
      cardiopulmonary bypass (CPB). Before CPB, the adrenomedullin level was the
      highest in the MV group, possibly due to chronic heart failure. Three hours after
      CPB, the plasma adrenomedullin level (pg/ml) increased to 1712.7 +/- 498.4 in the
      CY group, 167.6 +/- 26.4 in the PH group, and 1404.3 +/- 313.7 in the MV group,
      the level in the PH group being significantly lower than the rest. In the PH
      group, there was statistically significant negative correlation between the mean
      pulmonary arterial pressure at the preoperative catheter study, and the
      adrenomedullin level 3 h after CPB. These results illustrate that the
      adrenomedullin level increased after CPB, but that the increase was less marked
      in the PH group, implying that where the pulmonary vasculature was damaged most,
      this results in increased vasoconstriction.

PMID- 9778719
TI  - Effects of the combinations propofol/alfentanil and midazolam/fentanyl on blood
      pressure and contact phase system during coronary surgery.
AB  - Perioperative haemodynamic changes leading to severe circulatory problems during
      open-heart surgery still represent dreaded complications. The aim of this study
      was to examine the relationship between the use of applied anaesthetic agents and
      alterations of the contact phase of the intrinsic blood-clotting system, as
      changes within the kallikrein-kinin system can lead to a fall in blood pressure.
      In a randomized study, parameters of the kallikrein-kinin system, coagulation and
      fibrinolysis were determined for 36 patients with aortocoronary bypass
      operations. The patients had been given either midazolam/fentanyl or
      propofol/alfentanil to maintain anaesthesia. Perioperative blood pressure values
      were registered at seven fixed points. The measured values of the factor XIIa
      like activity and the kallikrein-like activity suggested a higher activation of
      the contact phase, when propofol/alfentanil was given. From the start of the
      extracorporeal circulation (ECC) to the end of the operation, the kallikrein-like
      activities in the propofol/alfentanil group were significantly higher than those
      of the midazolam/fentanyl group. Also, the results of the kallikrein inhibition
      capacity and the indicators of fibrinolysis (t-PA and D-dimers) indicate a
      stronger activation of the contact phase--at least at the beginning of
      recirculation--and as a result of it, a stronger fibrinolysis within the
      propofol/alfentanil group. In addition, the hypotensive side-effects differed
      significantly between the two groups. Patients receiving propofol/alfentanil
      needed the triple amount of antihypotonicum to maintain the mean arterial blood
      pressure above 75 mmHg. With the results of this study, a correlation between the
      application of propofol/alfentanil, contact phase activation, with activation of
      the kallikrein-kinin-bradykinin system and the observed hypotension, can be
      presumed.

PMID- 9778720
TI  - Testing neonate-infant membrane oxygenators with the University of Texas neonatal
      pulsatile cardiopulmonary bypass system in vitro.
AB  - Neurologic complications are already well documented after cardiopulmonary bypass
      (CPB) procedures in neonates and infants. Physiologic pulsatile flow CPB systems
      may be the alternative to the currently used steady-flow CPB circuits. In
      addition to the pulsatile pump, a membrane oxygenator should be chosen carefully,
      because only a few membrane oxygenators are suitable for physiologic pulsatile
      flow. We have tested four different types of neonate-infant membrane oxygenators
      for physiologic pulsatility with The University of Texas neonate-infant pulsatile
      CPB system in vitro. Evaluation criteria were based on mean ejection time,
      extracorporeal circuit (ECC) pressure, and upstroke of dp/dt. The results
      suggested that the Capiox 308 hollow-fibre membrane oxygenator produced the best
      physiologic pulsatile waveform according to the ejection time, ECC pressure, and
      the upstroke of dp/dt. The Minimax Plus and Masterflo Infant hollow-fibre
      membrane oxygenators also produced adequate pulsatile flow. Only the Variable
      Prime Cobe Membrane Lung (VPCML) Plus flat-sheet membrane oxygenator failed to
      reach the criteria for physiologic pulsatility. Depending on the oxygenator used,
      the lowest priming volume of the infant CPB circuit was 415 ml and the highest
      520 ml.

PMID- 9778721
TI  - Experimental evaluation of the Dideco D903 Avant 1.7 hollow-fibre membrane
      oxygenator.
AB  - Membrane oxygenators have now gained wide acceptance. A new hollow-fibre membrane
      oxygenator, the Dideco D903 Avant 1.7, with an optimized membrane surface (1.7
      m2) and a wavy blood flow pattern, was tested for gas transfer and blood path
      resistance in a standardized setting with surviving animals. Three calves (mean
      body weight 63.29 +/- 2.9 kg) were connected to cardiopulmonary bypass by jugular
      venous and carotid arterial cannulation, classic roller pump and the Dideco D903
      oxygenator with a mean flow rate of 53 +/- 0.1 ml/kg/min for 6 h. After this
      time, the animals were weaned from the CPB and thereafter from the ventilator.
      After 7 days, the animals were killed electively. Blood gas analysis was
      performed before bypass, after mixing (10 min) and then hourly for the 6 h of
      perfusion. Further samples were taken 30 min (spontaneous breathing) and 60 min
      after bypass (extubated). Physiological blood gas values could be maintained
      throughout perfusion in all animals. Mean arterial oxygen saturation varied
      between 99.3% and 99.7% for the arterial side of the oxygenator compared to 64.6%
      and 71% for the venous side. The highest mean pressure drop through the
      oxygenator was 54 mmHg. Postbypass blood gas analysis showed physiological values
      and no evidence of major lung trauma or pulmonary oedema in relation to the 6 h
      perfusion. The hollow-fibre membrane oxygenator, Dideco D903, offers excellent
      gas exchange capabilities and a low pressure drop under experimental conditions,
      despite reduced membrane surface area. The post mortem examination did not show
      any deleterious lesion.

PMID- 9778722
TI  - Clinical evaluation of setting pump occlusion by the dynamic method: effect on
      flow.
AB  - Pump manufacturers recommend setting roller pump occlusion such that the level of
      a 100 cm column of crystalloid drops 2.5 cm/min (Sarns, 8000 Modular Perfusion
      System, operator's manual, roller pump software version 2.3L. May 1993; 2.1
      2.14). Though this almost occlusive setting ensures accurate pump flow, it has
      been shown to cause more hemolysis than nonocclusive pumps (Noon GP, Kane LE,
      Feldman L et al. Reduction of blood trauma in roller pumps for long-term
      perfusion. World J Surg 1985; 9: 65-71). We conducted a clinical study (n = 19)
      to compare the standard occlusion method with the dynamic method and to determine
      the accuracy of flow for the nonocclusive pump. Standard occlusion was set by
      clamping the pump tubing distal to the arterial line filter and timing the drop
      in pump outlet pressure as indicated by a pressure transducer connected to the
      filter. The occlusion setting, expressed in mmHg/s, was recorded for each roller
      at two specific points along the raceway. The pump was then set nonocclusively
      with the dynamic method using the Better Header (BH) (Circulatory Technology,
      Oyster Bay, NY, USA). Readings of the change in pressure in the same two selected
      points on the raceway were taken. The latter was repeated after discontinuation
      of bypass. Flow was recorded throughout the procedure from both roller pump
      output display and a flow meter (Model #109 Transonic, Ithaca, NY, USA). The
      average drop in pump outlet pressure for the standard method was 1.3 +/- 4.0
      (range 0-18 mmHg/s), and for the dynamic method was 38 +/- 28 (range 1.2-89
      mmHg/s). Off bypass, the average reading was 44 +/- 38 (range 2.0-103 mmHg/s).
      Regression analysis indicates that patient flow, when corrected for retrograde
      flow by the dynamic method, equals 1.003 x revolutions per minute + 40 ml/min (r2
      = 0.964). The average error between indicated pump flow, corrected for retrograde
      flow, was -1% (range from -6.7 to 6.6%). We conclude that the BH allows
      nonocclusive setting (30 times less than our standard method) without sacrificing
      pump flow accuracy.

PMID- 9778723
TI  - Adenoviral inhibitors of the apoptotic cascade.

PMID- 9778724
TI  - Genetic dynamics of Salmonella typhi--diversity in clonality.

PMID- 9778725
TI  - Endosymbioses: cyclical and permanent in evolution.

PMID- 9778726
TI  - Genomics in infectious diseases: approaching the pathogens.

PMID- 9778727
TI  - What makes a thermophile?

PMID- 9778728
TI  - Interdependence of mycobacterial iron regulation, oxidative-stress response and
      isoniazid resistance.
AB  - Iron is an essential cofactor for vital functions in microorganisms. Bacterial
      pathogens have developed efficient iron-acquisition systems to counteract the
      defensive sequestration of iron by their hosts. In mycobacteria, the recently
      described protein, IdeR, negatively controls iron-uptake systems. This protein
      also has a role in the oxidative-stress response, as well as in resistance to the
      frontline antimycobacterial drug isoniazid.

PMID- 9778729
TI  - Studying M cells and their role in infection.
AB  - In addition to sampling antigens, M cells are a common route for pathogen
      invasion. Recent studies have partly defined the mechanisms by which pathogens
      interact with and exploit M cells as a gateway into the host. New research tools
      are facilitating studies on M cell infection, differentiation and function.

PMID- 9778730
TI  - Kinase-phosphatase competition regulates Bacillus subtilis development.
AB  - The major regulator of sporulation initiation in Bacillus subtilis is the
      phosphorelay, a multicomponent signal transduction system. A myriad of signals,
      both positive and negative, from the environment, cell cycle and metabolism is
      received and interpreted by the phosphorelay and integrated through the opposing
      activity of protein kinases and protein aspartate phosphatases to create an
      extremely sophisticated regulatory network.

PMID- 9778731
TI  - The great escape: structure and function of the autotransporter proteins.
AB  - The autotransporters, a family of secreted proteins from Gram-negative bacteria,
      possess an overall unifying structure comprising three functional domains: the
      amino-terminal leader sequence, the secreted mature protein (passenger domain)
      and a carboxy-terminal (beta-) domain that forms a beta-barrel pore to allow
      secretion of the passenger protein. Members of this family have been implicated
      as important or putative virulence factors in many Gram-negative pathogens.

PMID- 9778732
TI  - [Current concept of structure and function of the Golgi apparatus. On the 100
      anniversary of the discovery by Camillo Golgi].
AB  - The paper is a brief review of the current data on the structure and function of
      the Golgi apparatus since its discovery till the recent investigations, including
      the works published in 1997. Apart from reviewing the electron microscopy level
      of the structure of the Golgi apparatus, the data are considered on its molecular
      and supramolecular organization. The paper analyses critically the proposed
      mechanisms of the intracellular transport of proteins and their processing and
      modifications in the Golgi apparatus both in terms of the vesicular theory and in
      a model based on the gradual maturation of the cis-cistern and its transformation
      to the trans-cistern (i.e. its propagation from one pole to the other, a so
      called "progression"). Experimental data are described, which disagree with the
      current models of the intracellular transport. Based on the literature and
      authors' own data, a modified model of the intracellular transport is proposed.
      This model eliminates, to a degree, the contradictions present in the models
      discussed above.

PMID- 9778733
TI  - [Cytophotometric determination of non-heme iron content in hepatocytes. I. Effect
      of cell separation techniques on iron content].
AB  - To study conditions of the preservation of non-heme iron (3+) in hepatocytes,
      experiments were performed on rats fed with the diet supplemented with 2%
      carbonyl iron. The cells were isolated by a collagenase method (an enzymatic
      method) or by a treatment of the tissue with the phosphate buffer (a nonenzymatic
      method). When using the enzymatic method, the main steps of obtaining
      preparations-smears were analysed: perfusion of the organ, subsequent washing out
      of the cells from collagenase, mounting of the smear on the object glass. When
      using the non-enzymatic method, such steps were an incubation of the tissue
      pieces in the isolation solution and mounting of the smears. It has been found
      that the enzymatic isolation method results in practically no losses of iron from
      the cells if the perfusion lasts for 20 min. A slight loss (10-12%) of the Perls'
      stained iron can occur during the initial 30 min of the washing out of the cells
      from collagenase. This step is not accompanied by any morphological changes of
      the cells; their viability, according to the trypan test, is 70-87%. The iron
      release from the cells rises with decrease in the viability of hepatocytes. It
      has been shown that the greatest losses of iron can occur at the mounting step
      when the cells are submitted to a substantial mechanical effect. When the
      nonenzymatic method is applied, the incubation of the cells in the phosphate
      buffer for up to 2 hr causes no marked morphological changes revealed in the
      light microscope; however, the cell viability is very low (about 1%). The
      preservation of iron in the cells is lower when using the nonenzymatic than the
      enzymatic method. Thus, for cytophotometric determinations of the iron content in
      hepatocytes, the collagenase method of isolation of cells is recommended.

PMID- 9778734
TI  - [Cytophotometric determination of non-heme iron in hepatocytes. II. Effect of
      fixation on the cell iron content].
AB  - The study deals with the effect of different fixatives, such as absolute
      methanol, 96% ethanol, 10% buffered neutral formalin, as well as mixtures:
      methanol-formalin-acetic acid and ethanol-formalin-acetic acid (Tellesnitsky's
      solution) on preservation of iron in isolated hepatocytes of rats on a diet with
      addition of 2% carbonyl iron. The iron preservation in cells, on application of
      different fixatives and performance of Perls' reaction, was evaluated by the
      intensity of cell staining that was measured using cytospectrophotometer. The
      best preservation of iron in cells has been achieved when using alcohol fixatives
      only. Fixation of preparations with the methanol-formalin-aceticacid mixture also
      produced no decrease in the iron content in hepatocytes, however, morphology of
      the stained cells was much worse than after methanol and ethanol fixation.
      Fixation with Tellesnitsky's solution resulted in a 36% reduction of the cellular
      iron content, whereas fixation with 10% neutral formalin reduced iron content by
      58%, as compared with methanol fixation. A prolongation formalin fixation from 10
      min to 24 hr had no effect on the intensity of Perls' reaction.

PMID- 9778735
TI  - [Invasion of Escherichia coli A2 induces reorganization of actin microfilaments
      in Hep-2 cells].
AB  - Bacteria of spontaneously isolated non-pathogenic strain E. coli A2 have been
      previously shown to produce a new proteinase, referred to as protease ECP 32,
      which specifically cleaves actin (Khaitlina et al., 1988; Matveyev et al., 1996).
      Similar proteinase activity was found in revertants of Shigella flexneri L-forms.
      In this work immunofluorescence and electron microscopy were used to address a
      question of whether E. coli A2 can invade epithelial cells similarly as it has
      been demonstrated for Sh. flexneri. Infection of Hep-2 cells with E. coli A2
      resulted in bacterial invasion of the cells followed by cytoskeleton
      reorganization. On one end of intracellular bacteria bundles of actin filaments
      resembling a comet-like tail were observed. Bacteria of referent strain CCM 5172,
      not producing protease ECP 32, were not taken up by the cells. These data suggest
      that protease ECP 32 may be involved in the process of bacterial invasion and
      cytoskeleton reorganization.

PMID- 9778736
TI  - [Functional morphology of nucleolus organizer regions of chromosomes and nucleoli
      in human multiple myeloma cell lines. I. Variation of the morphology and silver
      staining of nucleolus organizer regions of chromosomes in RMPI 8226 and U 266
      cell lines with different level of differentiation of during 7 days after cell
      passage].
AB  - The morphology and Ag-staining of nucleoli in human multiple myeloma cell lines
      RPMI 8226 and U 266, distinguished from each other in the differentiation degree,
      were quantitatively studied, and the production of immunoglobulins or their
      fragments by the line cells was evaluated throughout 7 days after cell seeding.
      The less differentiated cell line RPMI 8226 and the high differentiated cell line
      U 266 were revealed to differ in both the initial level of immunoglobulin
      production and dynamics of immunoglobulin accumulation in culture medium. The
      total number of Ag-stained nucleolar-organizer regions (AgNORs) per nucleus in
      cells RPMI 8226 was significantly higher than in cells U 266 in all times after
      seeding of the cells. In both cell lines changes in the quantity and shape of
      nucleoli and also in the total number of AgNORs per nucleus and pattern of AgNORs
      distribution within nucleoli correlated with the cell cycle phase. Relationships
      between morphofunctional changes in nucleoli and the differentiation degree and
      proliferative activity of the cells, and also between the number of Ag-positive
      nucleolar-organizing metaphase chromosomes and the functional activity of
      interphase AgNORs are discussed.

PMID- 9778737
TI  - [The role of intracellular pH in regulation of NS/O myeloma cell growth and
      death].
AB  - Measurements of intracellular pH (pHi) were taken in the course of NS/O myeloma
      cell proliferation, growth arrest and death. Cell proliferation was shown to take
      place within a wide range of various pHi values (6.8-7.2), in which cell death
      could also occur. In dense cultures, after ceasing proliferation the apoptosis
      pathway of cell death was activated practically without pHi changes. Both
      proliferation and cell death stimulation were noticed in serum-free medium with
      apoptosis prevalence up to 72 h. Apoptotic death occurred at various
      intracellular pH values within the range from 6.5 to 7.2. The data obtained
      provide the ground to suppose that in contrast to normal cells, the pHi value in
      NS/O myeloma tumor cells was not a regulator of their proliferation and death.
      The decrease of cell growth and increase of cell death can take place with put
      pHi alteration.

PMID- 9778738
TI  - [Variability of gamete thermoresistance and heat selection of gametes in frogs
      and molluscs].
AB  - The variability of heat resistance of gametes in amphibians and molluscs has been
      analysed in terms of the problem of direct thermal selection at presygotic stages
      of ontogenesis. A high variability in gamete heat resistance was revealed both
      within the frame of a population of animals and in a particular individual. The
      variability in gamete resistance of an individual animal was as great as 6-8
      fold, whereas that within a population reached 8-10 fold value. Because of this
      phenomenon, a similar heat damaging factor exerted on gametes of different
      individuals results in different effect towards developed offsprings. A high
      variability of gamete heat resistance makes possible an effective and widely
      modified heat selection of gametes both of various genotypes and of an individual
      genotype. Under certain conditions gametes may be subject to natural selection,
      eliminating some classes of gametes and gives preference to some others. Because
      of this process the ratio of various phenotypes in population of organisms
      developed from the selected gametes also changes. The selective elimination of
      gametes of poikilotherms is able to influence the genetical-physiological
      structure of population.

PMID- 9778739
TI  - [Formation and regulation of myosin light chain kinase and phosphatase complex in
      smooth muscle: the outlook].
AB  - Myosin kinase and phosphatase, phosphorylating and dephosphorylating regulatory
      light chain of myosin, are the key regulatory enzymes of smooth muscle. They are
      tightly associated not only with myosin filament but also with each other and,
      therefore, appear to form a functional complex which is responsible for
      regulation of contraction and relaxation of smooth muscle. In our recent studies
      we have shown that the complex includes the kinase with its activator
      (calmodulin; CM) and the phosphatase in a form of catalytic and targeting
      subunits. The targeting subunit, being a CM binding protein, links the catalytic
      subunit to the kinase and to CM in a Ca-independent manner. In solution, the
      kinase is not exclusively monomeric but also dimerise and forms small amounts of
      oligomers, and all these forms are in equilibrium with each other. The dimers are
      responsible for a cooperative activation of the kinase by CM as well as for its
      intramolecular autophosphorylation, while the oligomeric form is involved in
      kinase localization on the myosin filament and also participates in formation of
      the complex with phosphatase. A kinase related protein (telokin) acts as a very
      effective modulator of the oligomeric state of the kinase by transferring the
      oligomers into the dimers and/or monomers. Telokin was effectively releasing the
      kinase from myosin filaments and the phosphatase from the complex with resulting
      inhibition of myosin phosphorylation and acceleration of myosin
      dephosphorylation. These modulating effects were reversed by a very slow
      phosphorylation of telokin by the kinase.

PMID- 9778740
TI  - [Characterization of aldehyde dehydrogenase gene fragment from mung bean Vigna
      radiata using the polymerase chain reaction].
AB  - Two degenerate oligonucleotide sequence primers and polymerase chain reactions on
      total DNA have been utilized to clone on 651--bp gene fragment coding the central
      part of amino acid sequence of an earlier unknown aldehyde dehydrogenase (ALDH)
      from mung bean. The deduced partial amino acid sequence for this aldehyde
      dehydrogenase shows about 65% sequence identity to ALDHs of Vibrio cholerae
      Rhodococcus sp., Alcaligenes eutrophus and about 45% sequence identity to
      mammalian ALDHs 1 and 2, ALDHs of Aspergillus niger and A, nidulans, the betain
      aldehyde dehydrogenase from spinach. Alignment of the mung bean aldehyde
      dehydrogenase partial amino acid sequence with the sequence of 16 NAD(P)(+)
      dependent aldehyde dehydrogenases has demonstrated that all strictly conserved
      amino acid residues and all three conservative regions are identical.

PMID- 9778742
TI  - CHILD profile: an immunization registry and more--a new approach to tracking and
      surveillance. Children's Health, Immunization, Linkages and Development.

PMID- 9778741
TI  - [Effect of some DNA-intercalators and antioxidants on the phagosome- lysosome
      fusion and F-actin content in murine peritoneal macrophages].
AB  - Effect of DNA-intercalators ethidium bromide (EB, 0.005 and 0.015 mM) and
      dimidium bromide (DB, 0.005 and 0.010 mM) and antioxidative compounds
      acetylsalicylic acid (ASA, 0.05 and 0.50 mM) and beta-carotene (0.01, 0.02, 0.05
      mM) on the phagosome-lysosome (P-L) fusion and F-actin content in murine
      peritoneal macrophages were studied. EB, DB, ASA and beta-carotene were found to
      stimulate P-L fusion and the effect depending on the concentration of compounds
      tested. The strongest influence as evoked by 0.5 mM of ASA and 0.05 mM of beta
      carotene. The compounds tested enhanced the F-actin content in macrophages,
      especially by the action of beta-carotene (0.05 mM). The obtained data indicate a
      correlation between P-L fusion stimulation and F-actin content under the
      influence of compounds tested in murine peritoneal macropheages.

PMID- 9778743
TI  - Epidemiology of emerging pneumococcal drug resistance: implications for treatment
      and prevention.
AB  - Drug-resistant Streptococcus pneumoniae infection are becoming increasingly
      common throughout the world. These strains pose new challenges in the treatment
      of suspected pneumococcal infections, and they highlight the importance of
      limiting selection for resistant strains through judicious antibiotic use and
      preventing infection by immunization of persons at high risk. The clinical impact
      of drug-resistant S. pneumoniae infection has not been fully defined, but
      anecdotal reports suggest that outcome is poor for persons with drug-resistant
      pneumococcal meningitis. The American Academy of Pediatrics has recommended
      adding vancomycin to the treatment of suspected pneumococcal meningitis cases
      until the results of culture and susceptibility testing are available. Additional
      data are needed to determine the optimal empiric antibiotic regimen for
      nonmeningeal invasive pneumococcal infections. A 23-valent pneumococcal capsular
      polysaccharide vaccine can prevent many drug-resistant and susceptible invasive
      pneumococcal infections. The vaccine is recommended in the United States for
      persons at increased risk of pneumococcal infection due to certain medical
      conditions and for all persons > or = 65 years old. Vaccine efficacy for
      immunocompetent persons > or = 65 years is 75%. However, the vaccine is
      underutilized, and a substantial reduction in the morbidity and mortality
      associated with invasive pneumococcal infections is unlikely until the vaccine is
      used more widely among persons at risk for disease.

PMID- 9778744
TI  - Enhanced immune responses and resistance against infection in aged mice conferred
      by Flu-ISCOMs vaccine correlate with up-regulation of costimulatory molecule
      CD86.
AB  - Ageing is associated with a decline in immune function and our primary objective
      is to 'reverse' age-related decline in protective immune responses to vaccination
      by formulating vaccines in appropriate delivery systems. In this paper, we
      demonstrate that influenza vaccine formulated as ISCOMs is highly immunogenic and
      confers protection in aged mice, when compared to current influenza vaccine. The
      enhanced protection conferred by Flu-ISCOMs in aged mice correlates with the up
      regulation of co-stimulatory molecule, CD86 (B7.2) and to a lesser extent, CD80
      (B7.1) expression on antigen presenting cells.

PMID- 9778745
TI  - Pharmacists as vaccine advocates: roles in community pharmacies, nursing homes,
      and hospitals.
AB  - Pharmacists increasingly take on immunization roles for their communities:
      advocates, facilitators and immunizers. Between 50 and 94% of people who receive
      a pharmacist's recommendation to be immunized accept that recommendation. Over 5
      million doses of influenza vaccine per year are administered in pharmacies. In 25
      states, pharmacists are authorized to administer immunizations. More than 1000
      pharmacists were trained to immunize in 1997. Consultant pharmacists can
      recommend vaccines in nursing facilities in the course of monthly drug regimen
      reviews. People have exceptional access to pharmacist at a wide variety of hours.
      Pharmacy-based immunization training incorporates safeguards that mimic or exceed
      quality standards in public-health clinics.

PMID- 9778746
TI  - Induction of MHC class I-restricted CTL response by DNA immunization with
      ubiquitin-influenza virus nucleoprotein fusion antigens.
AB  - DNA vaccines have been shown to be an effective means of inducing cytotoxic T
      lymphocyte (CTL) responses in both young and aged mice. Better understanding of
      the pathways by which antigens encoded by DNA vaccines are processed and
      presented to CTL may allow for improvements in CTL responses in older animals.
      Since CTL recognize short peptides presented by MHC class I molecules, and since
      ubiquitin-dependent proteolysis is widely believed to be responsible for
      degradation of endogenously synthesized antigens and generation of these peptide
      ligands, we sought to use ubiquitin (Ub) conjugation to target influenza virus
      nucleoprotein (NP) antigen into the Ub-proteasome degradation pathway for MHC
      class I-restricted antigen processing and presentation. However, the addition of
      the Ub moiety did not affect the half-life of Ub-NP protein in transiently
      transfected human rhabdomyosarcoma (RD) cells. Moreover, the modifications of NP
      DNA vaccine with Ub conjugation did not affect their ability to induce a CTL
      response specific for the H-2Kd-restricted NP147-155 epitope, as assessed by both
      percent cytolysis in bulk CTL culture and by CTL precursor (CTLp) frequency in
      limiting dilution analysis (LDA). In contrast, the anti-NP antibody (Ab)
      responses were dramatically reduced in mice immunized with low doses (1
      microgram) of Ub-NP constructs, compared with mice immunized with wild-type NP
      DNA. These results demonstrate that Ub conjugation alone does not guarantee
      targeting of endogenously synthesized antigens for rapid degradation by
      proteasomes. Furthermore, the ability of ubiquintination to reduce Ab responses
      to NP without affecting CTL responses suggests that the Ub modifications result
      in a lower availability of full-length NP from transfected cells in vivo. The
      implications of these data on antigen presentation and cross-priming are
      discussed.

PMID- 9778747
TI  - A comprehensive influenza campaign in a managed care setting.
AB  - Group Health Cooperative, a large, membership-governed, staff model health
      maintenance organization (HMO), has designed a comprehensive influenza campaign
      for identifying, recruiting and vaccinating enrollees at increased risk for
      influenza-related complications. The Cooperative's Centre for Health Promotion is
      responsible for the overall planning, implementation and evaluation of the
      influenza campaign. The model for delivering influenza immunizations has been
      designed to build on the strengths and capabilities of a staff model HMO with
      sophisticated automated information systems. The model permits area medical
      centres (AMCs) and physicians to use the materials and intervention strategies
      generated by the Centre for Health Promotion, while at the same time allowing
      them flexibility to design and use their own intervention strategies to increase
      compliance. More importantly, the model reduces resource requirements on AMCs and
      physicians to plan and maintain internal immunization efforts. Recommendations
      for improving the influenza campaign are discussed.

PMID- 9778748
TI  - Cytokine production after influenza vaccination in a healthy elderly population.
AB  - Influenza vaccination is less efficacious in the elderly than in the young. To
      characterize this age-related decrease in immune response to influenza
      vaccination, antibody and cell-mediated responses to influenza vaccine were
      assessed before immunization and 4 weeks after vaccination of a population of 270
      healthy elderly individuals (mean age: 80.2 years) living in eight local
      continuing care retirement communities (CCRCs) and 30 young individuals (mean
      age: 27.8 years). The antibody titres produced against all three influenza
      strains increased significantly after vaccination in both the young and elderly
      (p < 0.0005); however, the young demonstrated significantly higher titres to all
      three strains than did the elderly (p < 0.03). Peripheral blood mononuclear cells
      (PBMC) cultured with influenza vaccine demonstrated significantly increased
      proliferation (elderly: p < 0.00005; young: p < 0.001) after vaccination, with
      proliferative responses in the young significantly higher than the elderly both
      before (p < 0.04) and after (p < 0.0005) vaccination. Similarly, IFN gamma
      production in these PBMC cultures increased significantly pre- to postvaccination
      in both young and elderly (young: p < 0.006; elderly: p < 0.00005), but the young
      produced more than the elderly both pre- and postvaccination (p < 0.0001).
      Following vaccination, PBMC production of IL-10 was higher in the young than in
      the elderly (p < 0.0015), while IL-6 production was comparable in both young and
      elderly individuals. Greater than 13% of the elderly population did not produce
      detectable IL-6, IL-10, or IFN gamma either before or after vaccination. The data
      show that the decreased cell-mediated and humoral responses to influenza
      vaccination of this healthy elderly population are accompanied by the production
      of lower levels of cytokines. A unique finding in this population of 270 healthy
      elderly was the association between a TH0 cytokine profile and intact immune
      responses to influenza vaccine. A similar relationship was not seen in the young.

PMID- 9778749
TI  - Multivalent pneumococcal capsular polysaccharide conjugate vaccines employing
      genetically detoxified pneumolysin as a carrier protein.
AB  - A genetically detoxified pneumolysin, pneumolysoid (PLD), was investigated as a
      carrier protein for pneumococcal capsular polysaccharide (CPS). Such a CPS-PLD
      conjugate might provide additional protection against pneumococcal infections and
      resultant tissue damage. A single point mutant of pneumolysin was selected, which
      lacked measurable haemolytic activity, but exhibited the overall structural and
      immunological properties of the wild type. PLD conjugates were prepared from CPS
      serotypes 6B, 14, 19F, and 23F by reductive amination. The structural features of
      free PLD, as well as the corresponding CPS-PLD, as assessed by circular dichroism
      spectroscopy, were virtually indistinguishable from the wild type counterpart.
      Each of the CPS monovalent and tetravalent conjugate formulations were examined
      for immunogenicity in mice at both 0.5 and 2.0 micrograms CPS per dose. Tetanus
      toxoid (TT) conjugates were similarly created and used for comparison. The
      resultant conjugate vaccines elicited high levels of CPS-specific IgG that was
      opsonophagocytic for all serotypes tested. Opsonophagocytic titres, expressed as
      reciprocal dilutions resulting in 50% killing using HL-60 cells, ranged from 100
      to 30,000, depending on the serotype and formulation. In general, the lower dose
      and tetravalent formulations yielded the best responses for all serotypes (i.e.,
      either equivalent or better than the higher dose and monovalent formulations).
      The PLD conjugates were also generally equivalent to or better in CPS-specific
      responses than the TT conjugates. In particular, both the PLD conjugate and the
      tetravalent formulations induced responses for type 23F CPS that were
      approximately an order of magnitude greater than that of the corresponding TT
      conjugate and monovalent formulations. In addition, all the PLD conjugates
      elicited high levels of pneumolysin-specific IgG which were shown to neutralize
      pneumolysin-induced haemolytic activity in vitro. As a result of these findings,
      PLD appears to provide an advantageous alternative to conventional carrier
      proteins for pneumococcal multivalent CPS conjugate vaccines.

PMID- 9778750
TI  - Responses to influenza vaccination in different T-cell subsets: a comparison of
      healthy young and older adults.
AB  - T-lymphocyte responses to influenza vaccination were measured in healthy young
      and older adult volunteers. All participants were vaccinated with the 1995-96
      trivalent influenza vaccine. Cytokine and granzyme B levels were measured in
      peripheral blood mononuclear cells (PBMC) cultures after virus stimulation, prior
      to and 4 and 12 weeks after vaccination. The major findings in the older adult
      group were the different types of helper T-cell (Th) responses to each of the
      vaccine strains of virus and a very poor cytotoxic T lymphocyte (as measured by
      granzyme B) response to vaccination. IL-10, which is produced in a Th-type 2
      response, was higher in PBMC stimulated with A/Texas/36/91 (H1N1) compared with
      A/Johannesburg/33/94 (H3N2); this difference was more marked in the PBMC from
      older compared with younger adults. In contrast, IL-2, which is produced in a Th
      type 1 response, was measured in the same cultures and was significantly higher
      in A/Johannesburg/33/94-stimulated PBMC. IFN- gamma levels were highest in the
      PBMC stimulated with B/Harbin/7/94. The greatest age-related difference was the
      level of granzyme B in all virus-stimulated PBMC from the young compared with the
      older adult group. The strain of influenza virus contained in the vaccine, as
      well as the age of the subject, appear to be very important determinants of the T
      cell response to vaccination.

PMID- 9778751
TI  - Immunogenicity and efficacy of DNA vaccines encoding influenza A proteins in aged
      mice.
AB  - Influenza is a leading cause of morbidity and mortality in older persons. The
      current influenza vaccine is only modestly successful, in part because of an age
      related decline in immunogenicity and also because it induces only type-specified
      immunity. To overcome this, we evaluated DNA vaccines encoding A/PR8/34
      haemagglutinin (HA) and nucleoprotein (NP) in young and aged BALB/c mice. Control
      mice were given formalin-inactivated A/PR8/34, control DNA, or a non-lethal dose
      of PR8. Aged mice given HA DNA developed slightly lower anti-HA serum antibodies
      than young mice; however, both young and aged mice were protected from a
      homotypic PR8 challenge. Following vaccination with NP DNA, both young and aged
      mice developed anti-NP bulk cytotoxic T-lymphocyte (CTL) activity and pCTL
      frequency similar to control animals. When challenged with a low dose of A/HK/68
      (H3N2) influenza virus, both young mice and aged mice showed significant
      protection as measured by inhibition of weight loss. When challenged with a
      relatively high dose of A/HR/68 (H3N2) influenza virus, however, the anti-NP
      vaccine only partially protected young mice and failed to protect aged mice.
      These data demonstrate that DNA-based vaccines are immunogenic in aged animals,
      but suggest that factors other than the age-related decline in CTL activity also
      contribute to the increased morbidity and mortality of influenza in the elderly.

PMID- 9778752
TI  - Evaluation of live, cold-adapted influenza A and B virus vaccines in elderly and
      high-risk subjects.
AB  - We have evaluated the use of live cold-adapted influenza A and B virus vaccines
      in the elderly. Cold-adapted influenza A and B virus vaccines are safe and
      modestly immunogenic in individuals over 65 years of age. However, our studies
      and those of other groups have shown that immune response to cold-adapted
      vaccines in this age group are modest. Administration of combined cold-adapted
      influenza A and inactivated influenza vaccine has resulted in slightly higher
      frequencies of local and systemic humoral immune responses than inactivated
      vaccine alone in some, but not all, studies. In a double-blind field trial
      conducted in nursing homes over a 3 year period, combined cold-adapted influenza
      A (H3N2) and trivalent inactivated influenza vaccine resulted in a 60% decrease
      (95% CI, 18-82%) in the rate of laboratory documented influenza A compared with
      inactivated vaccine alone. Further studies of multivalent cold-adapted influenza
      vaccines used in combination with inactivated vaccine should be performed.

PMID- 9778754
TI  - Postherpetic neuralgia in immunocompetent elderly people.
AB  - The most menacing complication of herpes zoster in immunocompetent elderly people
      is chronic pain or postherpetic neuralgia (PHN). The cardinal epidemiological
      feature of PHN is its striking relationship to aging. Among zoster patients over
      60 years old, estimates of the occurrence of PHN, defined as pain 1 month after
      rash onset, vary from 27 to 68%. The pathogenesis of PHN is incompletely
      understood but seems to involve varicella-zoster virus (VZV)-induced damage of
      peripheral afferent neurons and resultant changes in central afferent neurons and
      efferent pain-modulating neurons. PHN improves over time in many elderly
      patients, but an unfortunate subset experience of debilitating pain lasts for
      years. They experience constant and/or intermittent spontaneous pain and stimulus
      evoked pain such as allodynia or hyperpathia. The outcomes of this pain include
      fatigue, sleep disturbance, anorexia, depression, social withdrawal, impaired
      activities of daily living and profound lowering of quality of life. The
      management of PHN is hampered by two problems: (1) a uniformly effective
      treatment for PHN is not available (although tricyclic antidepressants, local or
      regional anaesthetics, capsaicin, opiates, anticonvulsants and physical therapies
      are sometimes useful); and (2) early antiviral therapy of zoster may be
      ineffective in preventing PHN, partly related to the fact that days of VZV
      replication and neuronal destruction have occurred by the time the patient
      reaches the doctor. A potential solution to the problem of PHN is the vaccination
      of elderly persons with the varicella vaccine to prevent or attenuate zoster or
      PHN.

PMID- 9778753
TI  - Characterization of pneumococcal specific antibodies in healthy unvaccinated
      adults.
AB  - Unlike the elderly, healthy middle aged adults are at relatively low risk of
      acquiring serious pneumococcal disease. An explanation that has been proposed is
      that people in this age group have significant amounts of serum antibody
      (primarily IgG2) that react with any pneumococcal capsular polysaccharide
      serotypes. The level of antibody can be as high as several hundred micrograms per
      milliliter of blood for some serotypes. A significant component of this
      reactivity is directed toward the conserved C-polysaccharide depletion. Even
      after C-polysaccharide depletion, which is included as a routine part of the
      assay to determine antibody levels, resting antibody levels in a normal healthy
      adult population can vary widely. We have analyzed the reactivity of serum from
      76 people to 16 pneumococcal capsular polysaccharide serotypes. The antibody
      reactivities to 13 of 16 serotypes are highly correlated with one another.
      Depletion of serum with C-polysaccharide and purified capsular polysaccharide
      inhibited antibody binding to type specific capsular polysaccharide. Cross
      serotype inhibition of antibody binding was also observed. This indicates that
      there are materials contained within the pneumococcal polysaccharides that
      contribute to the cross-reactivity of serum antibodies in people that have not
      been vaccinated with the pneumococcal vaccine.

PMID- 9778755
TI  - Efficacy of zanamivir for chemoprophylaxis of nursing home influenza outbreaks.
AB  - Despite vaccination, influenza remains a common of morbidity in nursing homes.
      Chemoprophylaxis of residents with currently available antivirals is not always
      effective and new agents effective against both influenza A and B are needed. In
      a randomized, unblinded pilot study, we compared 14 day chemoprophylaxis with
      zanamivir, an antiviral which inhibits influenza neuraminidase, to standard of
      care during sequential influenza A and influenza B outbreaks in a 735 bed nursing
      home. Influenza A outbreaks were declared on 6/14 epidemic units. Sixty-five
      volunteers on four epidemic units were randomized to zanamivir and on two
      epidemic units, 23 volunteers were randomized to rimantadine. During the 14 days
      of prophylaxis, only four new febrile respiratory illnesses were detected. One
      volunteer receiving rimantadine prophylaxis developed laboratory-confirmed
      influenza. Influenza B outbreaks were declared on 3/14 epidemic units. Thirty
      five volunteers on two epidemic units were randomized to zanamivir and 18
      volunteers on one epidemic unit were randomized to no drug. During the 14 days of
      prophylaxis, only one new febrile respiratory illness was detected. One volunteer
      randomized to receive no drug developed laboratory-confirmed influenza. Zanamivir
      appears comparably effective to standard of care in preventing influenza-like
      illness and laboratory-confirmed influenza in nursing homes, but requires further
      testing.

PMID- 9778756
TI  - Respiratory syncytial virus infection in older persons.
AB  - Respiratory Syncytial Virus (RSV) is an increasingly recognized cause of serious
      disease in older adults. RSV causes excess morbidity and mortality in older
      persons residing in nursing homes and in the community. The study of RSV in
      adults has been hampered by the lack of sensitive methods for the diagnosis of
      acute infections. Such tools are needed to better understand the epidemiology and
      immunology of RSV in adults. The immune status of older adults has begun to be
      explored and preliminary data indicates that low serum neutralizing antibody may
      predispose to symptomatic RSV infection and that a greater diversity of antibody
      titres may be seen in the elderly compared to young adults. PFP-2, a candidate
      RSV subunit vaccine, has been evaluated in healthy and institutionalized elderly
      and been found to be safe and immunogenic.

PMID- 9778757
TI  - Does magnesium chloride modify aldrin-induced neurotoxicity in rats?
AB  - Magnesium chloride (MgCl2) has been proposed for the treatment of seizures of
      different etiologies. The present study investigated the effect of MgCl2 on
      aldrin-induced seizures. Initially, 50 male rats received 60 mg aldrin/kg po and
      the effects were classified as muscular twitches, clonic convulsions or tonic
      clonic convulsions. Another group of 40 rats dosed with 60 mg aldrin/kg po
      received 0, 4, 8, or 12 mg MgCl2/kg i.m. The percentage of tonic-clonic
      convulsant rats that resulted from MgCl2 treatment were 90% at 0 mg/kg, 50% at 4
      mg/kg, 40% at 8 mg/kg and 20% at 12 mg MgCl2/kg. The percentage of survivors in
      the group receiving 12 mg MgCl2/kg was 80% while the control group had 20%
      survival. The clonic convulsions were not modified by MgCl2 treatment. Blood and
      brain concentrations of aldrin and dieldrin (metabolite of aldrin) did not differ
      among groups. The MgCl2 administration decreased the neuroexcitability induced by
      aldrin and increased survivability.

PMID- 9778758
TI  - Abortifacient effects of lodgepole pine (Pinus contorta) and common juniper
      (Juniperus communis) on cattle.
AB  - Lodgepole pine (Pinus contorta) and common juniper (Juniperus communis) contain
      high levels of isocupressic acid that has been identified as the abortifacient
      component of ponderosa pine needles in cattle. Therefore, the abortifacient
      potential of P contorta and J communis needles was tested in feeding trials with
      pregnant cattle. Cows (2 groups of 2 each) were fed by gavage 4.5-5.5 kg/d ground
      dry needles from either P contorta or J communis starting on gestation day 250.
      Isocupressic acid (ICA) levels in P contorta needles and J communis plant
      material were 0.8 and 2.0% (dry weight) respectively. Cows fed P contorta
      received a daily dose of 62-78 mg ICA/kg body weight and aborted after 8 and 10
      d. The 2 cows fed J communis received a daily dose of 190 and 245 mg ICA/kg body
      weight and aborted after 3 and 4 days respectively. All cows retained fetal
      membranes and had classical clinical signs of pine needle-induced abortion. Pinus
      ponderosa, P contorta, J communis, and Cupressus macrocarpa samples were also
      analyzed for the presence of myristate and laurate esters of 1,14-tetradecanediol
      and 1,12-dodecanediol. These lipid like compounds of P ponderosa have potent
      vasoconstrictive activity in a placentome perfusion assay and are proposed as
      possible abortifacients in cattle. Concentration of the vasoactive lipids were
      0.028% (P ponderosa), 0.023% (P contorta), 0.001% (J communis), and none detected
      (C macrocarpa). It was concluded that these compounds are not required for the
      plant material to be abortifacient in cattle.

PMID- 9778759
TI  - Betaine reduces hepatic lipidosis induced by carbon tetrachloride in Sprague
      Dawley rats.
AB  - Carbon tetrachloride-injected rats were given liquid diets with and without
      betaine for 7 d. Hepatic lipidosis was induced by 4 daily injections of carbon
      tetrachloride (CCl4). Animals were killed and their livers and blood taken for
      analysis of betaine, S-adenosylmethionine (SAM), betaine homocysteine
      methyltransferase (BHMT), triglyceride, alanine aminotransferase and aspartate
      aminotransferase. Liver samples were also processed and stained for histological
      examination. Supplemental betaine reduced triglyceride in the liver and
      centrilobular hepatic lipidosis induced by the CCl4 injections. In both the
      control and experimental groups receiving betaine, liver betaine, BHMT and SAM
      were significantly higher than in their respective groups not receiving betaine.
      This study provides evidence that betaine protects the liver against CCl4-induced
      lipidosis and may be a useful therapeutic and prophylactic agent in ameliorating
      the harmful effects of CCl4.

PMID- 9778760
TI  - Toxicity of methomyl following intravenous administration in the horse.
AB  - Methomyl (S-methyl-N-((methylcarbamoyl)oxy) thioacetimidate) toxicity was studied
      in horses using i.v. dosages from 0.01 to 3.0 mg/kg. Doses of 1-3 mg methomyl/kg
      produced increased GI motility and respirations, facial fasiculations,
      salivation, lacrimation and convulsions. The only effect at 0.5 mg/kg was
      increased GI sounds in 1/4 horses. This extensively used crop insecticide had
      been associated with episodes of morbidity and mortality and led to speculation
      that it was extremely potent to the horse. This was not supported by these
      clinical studies.

PMID- 9778761
TI  - Effects of simultaneous administration of desferrioxamine and tacrine in rats.
AB  - Tacrine (1,2,3,4-tetrahydro-9-aminoacridine), a reversible cholinesterase
      inhibitor, was effective in the treatment of Alzheimer's disease (AD). In turn,
      desferrioxamine (DFO), a chelating agent with ability to chelate iron and
      aluminum (Al), produced a 50% decrease in the rate of cognitive decline in
      patients with AD. Since combined therapy with tacrine and DFO might be more
      effective than individual administration of these drugs for the treatment of AD
      patients, this study evaluated the toxic effects of concomitant administration of
      tacrine and DFO to rats. Three groups of 8 rats each received the following
      treatments for 8 w: 80 mg DFO/kg/d i.m., 7.5 mg tacrine/kg/d po, or 80 mg
      DFO/kg/d i.m. +7.5 mg tacrine/kg/d po. A control group received distilled water
      by gavage daily and a 0.9% saline injection i.m. The administration of DFO +
      tacrine for 8 w did not increase most of the side effects caused by the
      individual DFO or tacrine administrations. These results open the possibility of
      considering the effectiveness of simultaneous administration of DFO and tacrine
      as a palliative treatment for AD patients.

PMID- 9778762
TI  - Residues depletion in egg after warfarin ingestion by laying hens.
AB  - Accidental ingestion of anticoagulant rodenticide bait by poultry rarely leads to
      clinical signs of poisoning, but represents a risk for the consumer because of
      potential residues in the laid eggs. An assay was conducted for a better risk
      assessment. Three groups of laying hens were given a single oral dose of 10, 30
      or 90 mg warfarin/kg BW. Eggs were collected for 14 d, and warfarin was analyzed
      by reversed-phase high-performance liquid chromatography. Warfarin was present in
      the white for 3 to 4 d following anticoagulant ingestion, while concentration
      increased in the yolk until the 5th or 6th d, and then gradually decreased. At
      the end of experimentation, warfarin was still detected at below 100 ng/g in the
      yolk of eggs in each group.

PMID- 9778763
TI  - Experimental intoxication by Myoporum laetum in cattle.
AB  - Myoporum laetum was collected in the counties of Rio Grande and Capao do Leao in
      winter and in Santa Vitoria in summer, autumn, winter and spring, in the state of
      Rio Grande do Sul and in the Department of Rocha, Uruguay, in winter and spring.
      The fresh green leaves were fed to 16 calves. Two calves that ingested the plant
      from Capao do Leao at 40 and 44 g/kg bw did not develop clinical signs. The other
      14 calves had depression, abdominal pain, ruminal atony, ocular and nasal serous
      discharge, and dry feces with blood and mucus. Four calves developed icterus.
      First signs appeared 24-72 h after ingestion, and clinical period varied from 2
      to 7 d. One animal had mild photosensitization. Calves dosed with 20 g/kg of
      plant from Santa Vitoria and 40 g/kg of plant from Uruguay had less severe
      clinical signs. All cattle recovered except 1 dosed with 40 g/kg of plant
      collected in winter in Santa Vitoria; it died 70 h after ingestion. Histologic
      lesions in the liver of this animal and in biopsies obtained 48 h after dosing
      other calves had centrilobular necrosis, sometimes extending to the midzonal
      region. Clinical signs and hepatic lesions were also observed in a calf dosed
      with 5 daily doses at 8 g/kg. Serum AST, GGT and bilirubin were increased. M
      laetum from Santa Vitoria was the most toxic for cattle, and the plant from
      Uruguay was the least toxic, suggesting variations in toxicity among plants from
      different regions.

PMID- 9778765
TI  - Fatal adverse event secondary to high osmolality contrast agent.
AB  - Adverse drug events secondary to iodinated contrast agents are of particular
      concern to all clinicians. Despite the availability of newer agents, the
      mortality rates remain unchanged. We describe a fatal adverse event secondary to
      use of the high osmolality agent iothalmate meglumine 30%. A 58-y-old healthy
      female with no previous history of drug or food allergy had cardiac arrest toward
      the end of the i.v. infusion of the contrast agent during a CT scan. The patient
      expired despite aggressive therapeutic measures.

PMID- 9778764
TI  - Effects of nutrient supplementation in beef cows of poor body condition fed
      snakeweed (Gutierrezia spp).
AB  - Two replicate trials determined the effects of dietary supplementation on
      snakeweed toxicity in beef cows of poor condition. Cows were stratified by weight
      and randomly assigned to 3 dietary treatments. Dietary treatments were control (n
      = 3/trial; medium quality hay, 9.49% crude protein), corn supplementation (n =
      3/trial; control diet + 628 g cracked corn), and protein supplementation (n =
      3/trial; control diet + 800 g 42% protein supplement). Corn and protein dietary
      treatments were fed to be isocaloric. Each trial consisted of 2 phases (68
      days/phase). Phase 1 consisted of dietary treatments without snakeweed. In phase
      2 dietary treatments contained snakeweed as 10% of the dry matter. Phase 1 and 2
      dietary treatments were isocaloric/isonitrogenous. Dry matter intake of the
      control diet was limited to 1.3% of body weight/d. Body condition score and back
      fat were measured on days 0, 21 and 68 of each phase. Serum samples were
      collected at the onset of each trial and on days 28, 42 and 56 of each phase.
      Serum bromosulphthalein (BSP) elimination half life (t1/2) was estimated during
      week 6 of each phase. Serum BSP elimination t1/2 was higher for the control diet
      versus corn and protein treatments. Increased blood urea nitrogen (BUN) was found
      by day 28 of phase 2. Serum total bilirubin increased by day 28 in phase 2
      compared to baseline for the control and corn dietary treatments. Additionally,
      serum indirect bilirubin was higher by day 28 in phase 2. Likewise, serum direct
      bilirubin increased during phase 2 on day 28 in the corn diet, but decreased by
      day 28 for the protein diet. Alkaline phosphatase levels were higher (P < 0.05)
      in the controls by day 28, but lower in the protein treatment by day 28 in phase
      2. Changes were noted during phase 2 for some of the serum clinical profiles;
      however, these changes appear due to dietary restriction. In contrast, changes
      during phase 2 point to possible hepatotoxic and renal toxic effects of
      snakeweed. Phase 2 data suggest a benefit of protein supplementation for
      improving animal tolerance to snakeweed.

PMID- 9778767
TI  - The case of the salad shooters: intravenous injection of wild lettuce extract.
AB  - Three young adult drug users obtained wild lettuce and valerian root, prepared a
      crude aqueous extract of the wild lettuce, and injected the extract i.v. One also
      injected an alcohol extract of the valerian root. All 3 rapidly became ill with
      fevers, chills, abdominal pain, flank and back pain, neck stiffness, headache,
      leucocytosis and mild liver function abnormalities, but recovered over the next 3
      d. Various literature and internet sources claim that wild lettuce has opiate
      properties not demonstrated in this case.

PMID- 9778766
TI  - Cardiac arrhythmia and betel nut chewing--is there a causal effect?
AB  - Betel nuts are widely ingested in many countries, including Taiwan. They
      stimulate various autonomic and CNS reactions, but there have been no reports of
      cardiac toxicity. We treated 2 patients with cardiac dysrhythmias thought due to
      betel nut chewing. In case 1, a 44-y-old previously healthy male presented with
      chest tightness, dyspnea, diaphoresis and palpitation immediately after chewing 1
      betel quid. He soon became breathless and died despite immediate cardiopulmonary
      resuscitation. In Case 2, a 28-y-old man suffered palpitations, epigastralgia,
      and chest distress following consumption of 4 betel quid. Paroxysmal
      supraventricular tachycardia was noted and terminated by repeated verapamil
      administration. The pharmacological properties of betel nuts and the time
      sequence of these cases raise the possibility of betel nut-induced cardiac
      dysrhythmias. The number of betel nut chewers in Taiwan continues to increase,
      suggesting there may be other cases of betel nut-related cardiac toxicities in
      the future.

PMID- 9778768
TI  - Unclear dose equals toxic dose.
AB  - Medication errors are a significant public health issue. Their frequency and
      severity are currently under increased scrutiny from many perspectives. In 1996,
      the National Coordinating Council for Medication Error Reporting and Prevention
      (NCCMERP) was established to promote the reporting, understanding, and prevention
      of medication errors. NCCMERP has published prescription writing recommendations
      to remedy error-prone aspects of prescription writing. An example of a
      hazardously written medication order and its possible toxicity is provided.

PMID- 9778769
TI  - Propylene glycol toxicosis in a mare.
AB  - Propylene glycol and mineral oil are commonly used in the veterinary profession
      for treatment of bovine ketosis and equine impactions, respectively. Accidental
      administration of 6.0 ml propylene glycol/kg of body weight in horses causes
      severe depression, ataxia and malodorous breath and feces. However, appropriate
      medical therapy can result in successful treatment of this toxicosis.

PMID- 9778770
TI  - A cluster of equine granulomatous enteritis cases: the link with aluminium.
AB  - A cluster of 6 cases of equine granulomatous enteritis is described. Aluminium
      was demonstrated in the tissues and lesions of these horses and in the intimal
      bodies of intestinal vessels. The relationship between granulomatous lesions,
      aluminium, acidity and invading microorganisms, particularly parasites, is
      presented and discussed.

PMID- 9778771
TI  - Frequency of post-poisoning exposure information provided to patients requiring
      emergency care.
AB  - Pediatric unintentional poisoning is common despite preventative efforts.
      Children who have had a poison exposure are at increased risk for subsequent
      exposure. The purpose of our trial was to determine how often poison prevention
      information is provided to child care providers in health care facilities (HCF).
      This was a prospective telephone survey of 100 cases of unintentional poisonings
      of children ages 1-5 y referred to a HCF. Excluded were cases of patients that
      had intentional or chronic exposures. Eighty cases received no prevention
      material; 20 cases received Poison Prevention Information. Ninety-three of the
      patients were discharged from the emergency department, 6 patients were
      discharged from a pediatric floor, and 1 was discharged from a Pediatric ICU.
      Follow up calls to home may be difficult after the patient is referred to a HCF
      and many families did not receive poison prevention materials. This study
      indicates the need for a poison prevention discharge packet to be distributed to
      provide uniform and complete poison prevention education.

PMID- 9778772
TI  - Cassia occidentalis toxicosis in heifers.

PMID- 9778773
TI  - Chemicals, children and research $'s.

PMID- 9778774
TI  - Culicoides (Diptera: Ceratopogonidae) associated with horses at Mogoditshane,
      Gaborone, Botswana.

PMID- 9778775
TI  - The in vitro motility response to various anthelmintics of third-stage larvae of
      Oesophagostomum spp. from pigs.
AB  - The in vitro activities of thiabendazole, levamisole, pyrantel, morantel and
      ivermectin against Oesophagostomum spp., the nodular worm of pigs, were
      determined and compared. The study was carried out using isolates of O. dentatum
      and O. quadrispinulatum, which had been defined in vivo. Infective larvae were
      exposed to the anthelmintics for 24 h and then placed in a micromotility meter.
      All the treatments significantly reduced the motility of the ensheathed L3
      larvae, but the micromotility meter was not able to differentiate between
      anthelmintic resistant and anthelmintic susceptible isolates.

PMID- 9778776
TI  - The effect of continuous drug exposure on the immune response of lambs challenged
      with drug-susceptible or drug-resistant nematode larvae.
AB  - Groups of lambs either with or without controlled-release albendazole (ABZ)
      capsules (CRCs) were challenged twice weekly for 6 weeks with either drug
      susceptible or drug-resistant Ostertagia circumcincta and Trichostrongylus
      colubriformis. Groups with and without CRCs remained unchallenged as controls.
      There was minimal establishment of drug-susceptible parasites of either species
      in those lambs with CRCs. However, drug-resistant parasites of both species
      established adult worm burdens in the presence of the capsules. The humoral
      immune response, as measured by the serum antilarval (L3) antibody (Ab) titre,
      was pooled for weeks 4-6 and compared for each group. With the exception of anti
      T. colubriformis Ab in group 2, anti-L3 Ab titres were significantly higher in
      all the parasite-challenged groups as compared to the control animals. Also, with
      the exception of anti-resistant O. circumcincta Ab levels in the CRC-treated
      animals (group 5), no significant difference was observed in Ab titres between
      the four groups challenged with either resistant or susceptible larvae. The
      results demonstrate the inability of CRCs to prevent establishment of drug
      resistant parasites and that immune stimulation is not inhibited by the capsules.

PMID- 9778777
TI  - Development and survival of infective larvae of gastrointestinal nematodes of
      cattle on pasture in central Kenya.
AB  - On a series of pasture plots, 2 kg pats of bovine faeces containing known numbers
      of strongylid (Haemonchus, Cooperia, Oesophagostomum and Trichostrongylus) eggs
      were deposited at intervals of 4 weeks from July 1995 to June 1996. The plots
      were sampled every 2 weeks after contamination and infective larvae were
      identified and counted. Larvae of all the genera developed throughout the year,
      but the pats exposed during the rainy season yielded more abundant larvae on the
      herbage. Irrespective of the season of deposition of the pats, larvae were found
      in larger numbers from 2 to 6 weeks after deposition and generally declined to
      below detectable levels within 12 to 16 weeks of contamination. The comparatively
      short survival times noted in this experiment may present opportunities for
      manipulation of the population dynamics of the gastrointestinal nematodes in the
      tropical environment of Kenya.

PMID- 9778778
TI  - An abattoir survey of gastrointestinal nematode infections in cattle in the
      central highlands of Kenya.
AB  - The gastrointestinal tracts of 672 crossbred cattle were obtained from various
      abattoirs in Kiambu District, Kenya from August 1992 to July 1993, and examined
      for the presence of gastrointestinal nematodes. Eight nematode species were found
      in 583 (86.8%) of the animals. The nematodes were, in order of prevalence:
      Haemonchus placei (67.0%), Cooperia pectinata (53.0%), Cooperia punctata (41.7%),
      Oesophagostomum radiatum (38.4%), Trichostronglyus axei (24.3%), Nematodirus
      helvetianus (19.6%), Trichuris globulosa (9.7%) and Strongyloides papillosus
      (3.6%). The intensity of the nematode infection was moderate; the mean burden
      being less than 7000 worms. H. placei accounted, on average, for 52.3% of the
      total burden. The total burden was least during the dry seasons and increased
      gradually during the rainy seasons. Adult H. placei persisted in the host
      throughout the year and there was no indication of hypobiosis. The heaviest
      gastrointestinal worm burdens were detected in 1.5- to 3-year-old animals. These
      findings are discussed with regard to their relevance for strategic control of
      gastrointestinal nematodes in cattle.

PMID- 9778779
TI  - Haematological and biochemical studies in broiler chicks fed ochratoxin and
      inoculated with inclusion body hepatitis virus, singly and in concurrence.
AB  - Day-old broiler chicks, which had been shown to be negative for maternal
      antibodies against inclusion body hepatitis (IBH) virus and for viral antigen in
      cloacal swabs, were divided into four groups of 20 chicks each. One group was fed
      ochratoxin-A at 0.5 ppm from 3 to 38 days of age, another group was inoculated
      with 1 ml of IBH virus containing 10(6.5) EID50 per 0.2 ml. A third group was
      given both ochratoxin-A and infected with IBH virus. The fourth group served as
      the control. Anaemia was observed in all three treated groups but the changes
      were more pronounced in the combined group. The biochemical changes also
      suggested a cumulative damaging effect by ochratoxin-A and IBH virus.

PMID- 9778780
TI  - Haematological and biochemical studies on experimental Theileria annulata
      infection in crossbred calves.
AB  - Administration of ground-up tick tissue stabilate (0.75 tick equivalent) by the
      subcutaneous route to crossbred calves aged 1 week to 1 month led to the
      development of acute theileriosis. Haematological studies revealed significant
      progressive decreases in haemoglobin concentration, packed cell volume and red
      blood cell count, whereas the total leukocyte count showed an initial non
      significant leukocytosis followed by a significant leukopenia. Analysis of serum
      revealed significant increases in levels of alanine aminotransferase, aspartate
      aminotransferase, alkaline phosphatase, creatinine kinase and gamma
      glutamyltransferase, and in the concentrations of uric acid, blood urea nitrogen
      and bilirubin. The concentrations of total protein, albumin, glucose, cholesterol
      and calcium showed non-significant decreases, while phosphorus decreased
      significantly during the terminal stages of the disease.

PMID- 9778781
TI  - PCR detection of lentiviral GAG segment DNA in the white blood cells of sheep and
      goats.
AB  - A PCR assay for the detection of small ruminant lentiviral gag DNA (provirus) in
      the white blood cells of sheep and goats was developed and compared with a
      serological test (AGIDT). A sample of the DNA prepared from the white blood cells
      in 3 ml of blood from 208 sheep and goats from 18 different flocks was subjected
      to PCR assay. One of 85 animals from flocks accredited under the Dutch national
      MVV/CAEV control programme was positive by PCR while none was positive by AGIDT.
      In infected flocks, the AGIDT appeared slightly more sensitive, but preliminary
      results show that the sensitivity of the PCR assay may be further improved by
      increasing the number of monocytes tested. The PCR assay, however, was clearly
      more sensitive in detecting animals in the early stages of infection. With the
      use of a set of mixed primers and probes, the assay was able to detect the
      variety of CAEV and MVV strains occurring in the field.

PMID- 9778782
TI  - Nucleotide sequence of the 4.3 kbp BamHI-N fragment of fowlpox virus FP9.
AB  - Nucleotide sequence analysis of the 4.3 kbp BamHI-N fragment of the fowlpox virus
      (FPV) genome revealed that it encodes 7 proteins with homology to vaccinia virus
      (VV) E11L, E10R, O1L, O3L, I1L, I2L and I3L encoded proteins. No evidence of FPV
      homolog of VV O2L could be found.

PMID- 9778784
TI  - The genome-linked protein (VPg) of southern bean mosaic virus is encoded by the
      ORF2.
AB  - The sequence of the 20 N-terminal amino acids of the viral protein (VPg) which is
      covalently attached to the genomic RNA of the bean strain of Southern bean mosaic
      virus (SBMV-B) has been determined. The obtained VPg sequence mapped to position
      327 to 346 of the SBMV-B ORF2 product, downstream of the putative protease domain
      and in front of the RNA-dependent RNA polymerase. Thus indicating that the
      sobemovirus genomic arrangement is similar to that of subgroup II luteoviruses.
      Comparison with other viral sequences revealed a high similarity with the
      sequence of the ORF2-product of the cowpea strain of SBMV (SBMV-C). No
      significant similarities were detected with amino acid sequences derived of other
      sobemoviruses or non-related viruses.

PMID- 9778783
TI  - Isolation, replication and polyhedrin gene sequence of an Israeli Helicoverpa
      armigera single nucleopolyhedrovirus.
AB  - A local strain of Helicoverpa armigera baculovirus was isolated from infected H.
      armigera larvae. Infectivity to Helicoverpa cells, restriction enzyme analysis
      and electron microscopy allowed its identification as a single embedded
      nucleopolyhedrovirus, designated HaSNPV-IS. Analysis of DNA replication, protein
      synthesis and polyhedrin expression in HaSNPV-infected cells located the late and
      very late phases of the viral cycle at 24 and 48 h after infection, respectively.
      The viral polyhedrin gene was isolated and characterized. It encoded for a
      polypeptide of 246 amino acid residues. A 32 kDa polypeptide was identified by
      immunoblot analysis using antipolyhedrin antiserum. The HaSNPV-IS polyhedrin DNA
      sequence revealed 99.4% of homology to the HzSNPV polyhedrin. The availability of
      this efficient replication system and the above knowledge paves the way to future
      genetic engineering of the HaSNPV.

PMID- 9778785
TI  - Construction of canine herpesvirus vector expressing foreign genes using a lacZ
      TK gene cassette as a double selectional marker.
AB  - An improved method for constructing canine herpesvirus (CHV) recombinants
      expressing foreign genes by using the lacZ-TK gene cassette as a double
      selectional marker was developed. A recombinant CHV carrying the lacZ-TK gene at
      a targeted gene locus was constructed and used as a parental virus for generating
      new recombinants. The parental virus formed blue plaques and was sensitive to TK
      specific drugs, while newly generated recombinants, in which the lacZ-TK gene was
      replaced with the desired foreign gene, become both resistant to the TK-specific
      drugs and formed white plaques. Recombinants were isolated by using the
      combination of drug selection and color selection. This improved method allows
      construction of recombinant CHV with great ease, because the drug selection can
      enrich the frequency of recombinant CHV from 0.01-0.1% to 10-80%. This method was
      employed to construct a recombinant CHV that expressed rabies virus (RV)
      glycoprotein (G protein).

PMID- 9778787
TI  - Complete inhibition of SIVmac replication by its capsid mutants.
AB  - Mutations were introduced into a genomic region encoding the C-terminal portion
      of Gag capsid protein of pathogenic simian immunodeficiency virus (SIVmac239).
      All the mutants generated were defective for virion production and were non
      infectious for monkey cells. They all efficiently suppressed the replication of
      wild type SIVmac in monkey cells. These results were in good agreement with those
      obtained for human immunodeficiency virus type 1, showing the importance of
      SIV/monkey model system for studies on Gag.

PMID- 9778788
TI  - Identification of the UL56 protein of herpes simplex virus type 1 within the
      virion by immuno electron microscopy.
AB  - Recently the UL56 protein of herpes simplex virus type 1 (HSV-1) was shown to be
      associated with the virion of HSV-1 as determined by Western blot analysis. The
      detection of the UL56 protein in infected cells and its association with virions
      of HSV-1 is of particular importance, pointing to a possible involvement of UL56
      protein in virus-host interactions. In order to investigate the properties of the
      UL56 protein further immuno-localization was performed using rabbit hyperimmune
      serum against fusion recombinant UL56 protein and purified virions of HSV-1
      strain F. The UL56 protein was detected in the HSV-1 virions by immuno gold
      negative staining.

PMID- 9778786
TI  - Nucleotide and predicted amino acid sequences of all genes encoded by the 3'
      genomic portion (9.5 kb) of respiratory bovine coronaviruses and comparisons
      among respiratory and enteric coronaviruses.
AB  - The 3'-ends of the genomes (9538 bp) of two wild-type respiratory bovine
      coronavirus (RBCV) isolates LSU and OK were obtained by cDNA sequencing. In
      addition, the 3'-end of the genome (9545) of the wild-type enteric bovine
      coronavirus (EBCV) strain LY-138 was assembled from available sequences and by
      cDNA sequencing of unknown genomic regions. Comparative analyses of RBCV and EBCV
      nucleotide and deduced amino acid sequences revealed that RBCV-specific
      nucleotide and amino acid differences were disproportionally concentrated within
      the S gene and the genomic region between the S and E genes. Comparisons among
      virulent and avirulent BCV strains revealed that virulence-specific nucleotide
      and amino acid changes were located within the S and E genes, and the 32 kDa open
      reading frame.

PMID- 9778789
TI  - The myxoma virus EcoRI-O fragment encodes the DNA binding core protein and the
      major envelope protein of extracellular poxvirus.
AB  - The nucleotide sequences of the myxoma virus gene homologs encoding the DNA
      binding core protein (MF17) and the major envelope protein of the extracellular
      poxvirus particle (MF13) have been localized to the myxoma virus 4 kB EcoRI-O
      fragment. The EcoRI-O fragment is located approximately 22 kb from the left end
      of the 163 kb DNA genome and encodes homologs of the F12L, F13L, F15L, F16L, F17R
      and E1L genes of the Copenhagen strain of vaccinia virus. The inferred amino acid
      sequences of the myxoma virus EcoRI-O encoded products have been compared to the
      protein databases to identify related proteins. The myxoma virus open reading
      frames MF12, MF15, MF16, MF17 and ME1 encode homologs of poxvirus specific
      proteins while the MF13 envelope protein also shares amino acid similarity with
      other poxvirus and cellular proteins.

PMID- 9778790
TI  - Sequence comparison of avian infectious bronchitis virus S1 glycoproteins of the
      Florida serotype and five variant isolates from Georgia and California.
AB  - The infectious bronchitis virus (IBV) spike glycoprotein S1 subunit is required
      to initiate infection and contains virus-neutralizing and serotype-specific
      epitope(s). Reported are the S1 gene nucleotide and predicted amino acid
      sequences for the Florida 18288 strain and isolates GA-92, CV-56b, CV-9437, CV
      1686, and 1013. These sequences were compared with previously published gene
      sequences of IBV strains, and phylogenetic relationships are reported. The S1
      amino acid sequence of Florida 18288 was 94.9% similar to the Connecticut strain,
      and GA-92 was 92.8% similar to the Arkansas 99 strain. S1 amino acid sequences of
      the California variants, CV-56b, CV-9437, and CV-1686, were 97.6-99.3% similar to
      one another and only 76.6%-76.8% similar to the Arkansas-type strains. Isolate
      1013, also from California, was 84.0% similar to Ark DPI and 77.9% similar to CV
      56b. When comparing 19 viruses isolated from the United States, sequence
      variations were observed between amino acids 55-96, 115-149, 255-309, and 378
      395. Similar regions are reported to be involved in virus-neutralizing and/or
      serotype-specific epitopes. These data demonstrate that variant IBV strains
      continue to emerge, and unique variants may circulate among poultry in
      geographically isolated areas.

PMID- 9778791
TI  - Complete nucleotide sequence analysis of a Western Pacific dengue-1 virus strain.
AB  - We have determined the complete nucleotide sequence and the deduced amino acid
      polypeptide sequence of the genome of a dengue-1 (DEN-1) virus strain isolated
      from a patient on Nauru in the Western Pacific in 1974 (West Pac 74). The
      complete genome is 10,735 nucleotides in length and contains a single long open
      reading frame of 10,176 nucleotides encoding a polyprotein of 3392 amino acids.
      When compared to DEN-1 Singapore S275/90, the nucleotide and amino acid sequence
      homology are 94% and 97.8%, respectively.

PMID- 9778792
TI  - Analysis of the equalization of inverted repeats and neurovirulence using a
      pseudorabies virus mutant strain altered at the Ul/Ir junction.
AB  - A recombinant pseudorabies (Aujeszky's disease) virus (PrV) designated as vE16lac
      was constructed by deleting a 3-kbp DNA segment spanning the junction of long and
      short components of the viral genome, and by replacing the deleted segment with a
      lacZ-expression cassette. The aim of constructing this mutant was (a) to
      determine whether the terminal repeat (Tr) can serve as a template for the
      regeneration of the internal repeat (Ir), and (b) whether this deletion causes a
      reduction in the neuroinvasiveness of the virus. To analyze the mechanism of
      equalization, revertant viruses were selected and structurally characterized from
      vE16lac infection of PK-15 cells, mice and pigs. Because all revertants acquired
      Ir sequences identical to that of the wild-type virus, the equalization process
      occurred using the Tr as a template to reconstitute the Ir. We also found that
      the recombinant virus vE16lac was virulent in both pigs and mice. The data are
      discussed in view of studies performed with similar PrV mutants by other authors
      (Rall et al., 1992, Dean and Cheung, 1995 and Dean et al., 1996).

PMID- 9778793
TI  - Genetic organization and DNA sequence of early region 4 of bovine adenovirus type
      3.
AB  - We have identified and sequenced 3614 nucleotides located at the extreme right
      end of the bovine adenovirus type 3 (BAV3) genome from map units 89.5-100.
      Analysis of the sequence revealed an inverted terminal repeat (ITR) of 195 bp,
      and identified five open reading frames (ORFs) designated ORF1, ORF2, ORF3, ORF4
      and ORF5. When compared with known E4 ORFs of other adenoviruses, ORFs 1, 2 and
      4, which code for proteins of 143, 69 and 143 amino acids respectively, were
      found to be unique to BAV3. ORFs 3 and 5, which code for proteins of 268 and 219
      amino acids respectively, showed partial homology to the E4 34 kDa protein of
      human adenovirus 2. Nucleotide sequence analysis also identified two potential
      TATA boxes upstream of ORF1 and a potential polyadenylation signal downstream of
      ORF5 suggesting that E4 transcripts may be 3' co-terminal.

PMID- 9778794
TI  - Candida rugosa lipases: molecular biology and versatility in biotechnology.
AB  - This review describes how the versatile Candida rugosa lipases (CRL) have
      extended the frontiers of biotechnology. As evidenced by the current literature,
      CRL claims more applications than any other biocatalyst. This review comprises a
      detailed discussion on the molecular biology of CRL, its versatile catalytic
      reactions, broad specificities and diverse immobilization strategies. It also
      discusses its role in the food and flavour industry, the production of ice cream
      and single cell protein, biocatalytic resolution of life-saving pharmaceuticals,
      carbohydrate esters and amino acid derivatives unobtainable by conventional
      chemical synthesis, potent biocide making, biosensor modulations, eco-friendly
      approach and bioremediation, biosurfactants in detergent making, and recently,
      cosmetics and perfumery.

PMID- 9778795
TI  - Transient mRNA responses in chemostat cultures as a method of defining putative
      regulatory elements: application to genes involved in Saccharomyces cerevisiae
      acetyl-coenzyme A metabolism.
AB  - To identify common regulatory sequences in the promoters of genes, transcription
      of 31 genes of Saccharomyces cerevisiae was analysed during the transient
      response to a glucose pulse in a chemostat culture. mRNA levels were monitored
      during the subsequent excess glucose, ethanol and acetate phases, while other
      conditions were kept constant. This setup allowed a direct comparison between
      regulation by glucose, ethanol and acetate. Genes with identical regulation
      patterns were grouped to identify regulatory elements in the promoters. In
      respect to regulation on glucose four classes were identified: no transcription
      under any of the conditions tested, no difference in regulation on glucose,
      induced on glucose and repressed on glucose. In addition, genes were found that
      were repressed or induced on ethanol or acetate. Sequence alignment of genes with
      similar regulation patterns revealed five new, putative regulatory promoter
      elements. (i) The glucose-inducible fermentation genes PDC1 and ADH1 share the
      sequence ATACCTTCSTT. (ii) Acetate-repression might be mediated by the decamer
      CCCGAG RGGA, present in the promoters of ACS2 and ACR1. (iii) A specific element
      (CCWTTSRNCCG) for the glyoxylate cycle was present in seven genes studied: CIT2,
      ICL1, MLS1, MDH2, CAT2, ACR1 and ACH1. These genes were derepressed on ethanol or
      acetate. (iv) The sequence ACGTSCRGAATGA was found in the promoters of the
      partially ethanol-repressed genes ACS1 and YAT1. (v) Ethanol induction, as seen
      for ACS2, ADH3 and MDH1, might be mediated via the sequence CGGSGCCGRAG.

PMID- 9778796
TI  - A highly conserved intraspecies homolog of the Saccharomyces cerevisiae
      elongation factor-3 encoded by the HEF3 gene.
AB  - A paralog (intraspecies homolog) of the Saccharomyces cerevisiae YEF3 gene,
      encoding elongation factor-3, has been sequenced in the course of the yeast
      genome project, and identified by database searching; this gene has been
      designated HEF3. Bioinformatic and Northern blot analysis indicate that the HEF3
      gene is not expressed during vegetative growth. Deletion of the HEF3 gene reveals
      no growth defects, nor any defects in mating or sporulation. A high copy 2 mu
      clone of HEF3 was constructed, and was shown to be unable to complement a null
      allele of yef3. Finally, an in vitro assay for ribosome-stimulated ATPase
      activity was performed with isogenic HEF3 and delta hef3 strains; no difference
      in biochemical activity could be detected in these strains. From these results,
      we conclude that the HEF3 gene does not encode a functional homolog of YEF3.

PMID- 9778797
TI  - Secretion and pH-dependent self-processing of the pro-form of the Yarrowia
      lipolytica acid extracellular protease.
AB  - The secretion and maturation of the acid extracellular protease (AXP) of the
      yeast Yarrowia lipolytica have been characterized using antiserum raised against
      this enzyme. A 42 kDa pro-enzyme form of AXP was identified from lysates of
      radiolabelled Y. lipolytica cells and found to contain no N-linked carbohydrate
      moieties. Using pulse-chase immune precipitation it was demonstrated that the AXP
      precursor was secreted into the extracellular medium where, under conditions of
      low pH, it underwent autocatalytic activation forming the mature enzyme.
      Conversion of the AXP pro-form in the presence of the protease inhibitor
      pepstatin indicated that an intramolecularly-catalysed reaction mechanism was
      involved in AXP maturation. Further evidence supporting the role of autocatalytic
      processing came from the side-chain specificity of mature AXP towards the
      oxidized B-chain of insulin.

PMID- 9778798
TI  - Functional analysis of yeast essential genes using a promoter-substitution
      cassette and the tetracycline-regulatable dual expression system.
AB  - A promoter-substitution cassette has been constructed that allows one-step
      substitution of chromosomal gene promoters for the tetracycline-regulatable tetO
      promoter in yeast cells, which uses kanMX4 as selective marker for geneticin
      resistance. Oligonucleotides for PCR amplification of the cassette are designed
      to allow homologous recombination through short flanking regions of homology with
      the upstream sequences of the chromosomal gene, upon transformation of target
      cells. By testing three essential genes of chromosome XV (YOL135c, YOL142w and
      YOL144w), the system causes tetracycline-dependent conditional growth of the
      cells, being modulatable by intermediate concentrations of the effector. Analysis
      of terminal phenotypes of the promoter-substituted cells in the presence of the
      antibiotic may facilitate functional analysis of essential orphan genes.

PMID- 9778799
TI  - New constructs and strategies for efficient PCR-based gene manipulations in
      yeast.
AB  - Gene disruption and tagging can be achieved by homologous recombination in the
      yeast genome. Several PCR-based methods have been described towards this end.
      However these strategies are often limited in their applications and/or their
      efficiencies and may be technically demanding. Here we describe two plasmids for
      C-terminal tagging of proteins with the IgG binding domain of the Staphylococcus
      aureus protein A. We also present simple and reliable strategies based on PCR to
      promote efficient integration of exogenous DNA into the yeast genome. These
      simple methods are not limited to specific strains or markers and can be used for
      any application requiring homologous recombination such as gene disruption and
      epitope tagging. These strategies can be used for consecutive introduction of
      various constructs into a single yeast strain.

PMID- 9778800
TI  - Cloning and sequence of a 3.835 kbp DNA fragment containing the HIS4 gene and a
      fragment of a PEX5-like gene from Candida albicans.
AB  - We have isolated the Candida albicans HIS4 (CaHIS4) gene by complementation of a
      his4-34 Saccharomyces cerevisiae mutant. The sequenced DNA fragment contains a
      putative ORF of 2514 bp, whose translation product shares a global identity of
      44% and 55% to the His4 protein homologs of S. cerevisiae and Kluyveromyces
      lactis, respectively. Analysis of CaHIS4 sequence suggests that, similarly to S.
      cerevisiae HIS4, it codes for a polypeptide having three separate enzymatic
      activities (phosphoribosyl-AMP cyclohydrolase, phosphoribosyl-ATP
      pyrophosphohydrolase and histidinol dehydrogenase) which reside in different
      domains of the protein. A C. albicans his4 strain is complemented with this gene
      when using a C. albicans-S. cerevisiae-Escherichia coli shuttle vector, thus
      enabling the construction of a host system for C. albicans genetic manipulation.
      In addition, upstream of the sequenced CaHIS4 sequence, we have found the 3'
      terminal half of a gene encoding a PEX5-like protein.

PMID- 9778802
TI  - [The structure of the cortical-subcortical relationships of the cerebral
      electrical processes during a motor polarization dominant].
AB  - Under conditions of rabbit chronic experiments, it was shown by means of the
      spectral-coherence analysis that the motor polarization dominant formed by the
      application of DC anode to the sensorimotor cortex produced a novel structure of
      the intercentral relations between electrical processes not only in the ipsi-,
      but in the contralateral brain hemisphere. A certain "isolation" of the primary
      focus was observed in the cortex of the "dominant" hemisphere, which was
      manifested in a decrease in its delta-range coherent relations with the other
      cortical areas. At the dominant optimum (in interstimulus intervals), an
      interhemispheric asymmetry in the EEG coherence spectra was observed in the delta
      band between the sensorimotor cortical areas, ventroposterolateral thalamic
      nuclei, and CA3 fields of the dorsal hippocampi. The asymmetry increased during
      the testing auditory stimulation. Development of the alpha- and beta-band
      interhemispheric asymmetry in the structures in question coincided with
      realization of the motor "dominant" reaction and was suggested to be associated
      with movement organization.

PMID- 9778801
TI  - [The motivational dominant and goal-directed behavior].
AB  - The experimental studies of motivational dominants of thirst and hunger and
      "polarization" motor dominant as well as the analysis of formation of the I- and
      II-type conditioned responses lead to the conclusion that discontinuation of a
      motivational dominant plays a key role in goal-directed behavior. The activation
      of backward connections between corresponding centers forms the basis for
      realization of goal-directed behavior.

PMID- 9778803
TI  - [A coherence analysis of the electrical activity of the rabbit brain during the
      creation of a "polarization" hunger dominant].
AB  - In the process of formation of "polarization" hunger dominant under the action of
      weak direct current on the structures of lateral hypothalamus and sound
      stimulation, the coherence between the potentials of the right parietal cortical
      area and the frontal areas of both hemispheres increases in the low-frequency
      band. At the same time, the coherence between electrical activity led from the
      other cortical areas under study decreased. An increase in coherence is observed
      between the potentials led from the lateral hypothalamus and frontal cortical
      areas of both hemispheres in contrast to a decrease in coherence between the
      electrical activity of the lateral hypothalamus and parietal cortex. Coherence
      between potentials recorded in the ventromedial hypothalamus and electrical
      activity of all the studied cortical areas increases (mainly, in the low
      frequency range).

PMID- 9778804
TI  - [The interaction in the motor cortex of 2 foci of a "polarization" dominant].
AB  - The effect of sequential applications of the weak anode DC (0.5-3 mcA) to the
      areas of fore- and hindlimb representation in the motor cortex was studied in
      waking unrestrained rabbits. This procedure formed two excitation foci with the
      dominant properties, i.e., different afferent stimuli (sound, light) produced the
      dominant behavioral reaction (limb movement). The cooperative inhibition of the
      dominant foci was observed in the process of formation of the second focus in
      different time intervals. The second focus inhibited the primary focus for a
      rather long-term period, and then the mutual inhibition of the foci acquired the
      reciprocal character. The obtained results testify to excitation redistribution
      in the motor cortex during the action of weak anode DC on the motor cortex.

PMID- 9778805
TI  - [A coherence analysis of the electrical activity of the rabbit brain during a
      shift in the dominants].
AB  - Coherence between the electrical activity in the sensorimotor (forelimb and
      blinking centers) and visual cortical areas, as well as VPL of the left and right
      thalamus was studied during creation of the motor defensive dominant by the
      serial electrical forelimb stimulation against the background of the blinking
      dominant (produced by the serial eye stimulation with an air stream). An increase
      in EEG coherence in the delta-range was observed in the structures which realized
      the defensive reflex. Formation of the latent defensive dominant destroyed the
      typical for the dominant state relationships of potentials in the cortical
      structures responsible for realization of the blinking reflex.

PMID- 9778806
TI  - [The thermal activity of the rabbit brain in motivational states of hunger or
      thirst].
AB  - Motivational states of hunger or thirst in rabbits were produced by the relevant
      deprivation of different duration (24 and 48 h). The distribution of brain
      thermal fields was studied by the method of thermoencephaloscopy. The thermal
      asymmetry was observed in the states of thirst and hunger the temperature of the
      left hemisphere being higher. Generalization of the brain temperature reaction
      depended on the level of motivational excitation. The interhemispheric brain
      asymmetry with higher temperature in the left hemisphere in the states of food
      and drinking deprivation had a pronounced trace effect, i.e., persisted for some
      time after satisfaction of the corresponding need. Evidently, the
      interhemispheric asymmetry with higher temperature of the left hemisphere
      reflects its predominant activation in the studied states.

PMID- 9778807
TI  - [The time distribution of the spike train activity of the neurons in the rabbit
      sensorimotor cortex during a rhythmic motor dominant].
AB  - A stationary excitation focus produced in rabbit cortex by rhythmical
      electrodermal paw stimulation was revealed by presentation of testing sound
      stimuli, which were earlier indifferent for an animal. The multiunit activity in
      the sensorimotor cortex was recorded. The neuronal pairs were detected with
      correlated discharges. Analysis of discharges in such pairs revealed the dominant
      incidence of conjugated impulses with the interval equal or close to 2 s, if the
      focus had been created by stimulation with the rhythmic interval 2 s. The
      dominant interval between discharges in a conjugated pair of neurons was equal of
      close to 3 s, if the rhythmic stimuli positions had been spaced 3 s. It was shown
      that the rhythmical nature of the dominant focus was maintained at the level of
      neuronal interactions, i.e., was of a systemic character. The acquired rhythm in
      conjugated cell activity was observed not only during summation in the moment of
      excitation transmission to the effector (i.e., when the dominant realized itself
      in the motor reaction), but within the periods between the testing stimuli.

PMID- 9778808
TI  - [Shifts in the constant potential in the structures of the rat brain in focal
      ischemia and systemic hypoxia].
AB  - The role of spreading depression (SD) in the development of ischemic brain damage
      in rats was studied in two models: focal cortical ischemia provoked by a
      photothrombotic occlusion of the middle cerebral artery (MCA) and systemic
      hypoxia induced by breathing with 0.8% carbon monoxide (CO). Spontaneous cortical
      SD waves occurring during illumination were found to delay the irreversible MCA
      occlusion. Thrombosis was probably prevented by episodes of striking vasodilation
      and hyperemia lasting for 1-2 min and accompanying every SD wave. The SD-induced
      hyperemia after permanent MCA occlusion seems to improve the oxygen supply of the
      penumbra zone. During hypoxia induced by one-hour respiration with 0.8% CO, COHb
      saturation of the blood reached 50-60%. SD waves occurred in different brain
      regions of lightly anesthetized rats (pentobarbital, 20 mg/kg) changed under the
      above conditions into prolonged depolarizations (HDs) which led to a substantial
      increase in animals' mortality (60%). The SDs evoked in the cortex and
      hippocampus of deeply anesthetized rats (pentobarbital, 50 mg/kg) showed that
      hippocampus became highly vulnerable by CO hypoxia. Duration of the SD-provoked
      HDs often reached 30-60 min after a single SD wave. Decreased cell density was
      found in CA1 area of the hippocampus 20-30 days after the CD-enhanced CO hypoxia.
      Cerebrolysin (2.5 ml/kg daily, during 10 days) prevented from severe hippocampal
      injury (formation of granulomas) usually seen in the left hemisphere of rats not
      treated with cerebrolysin.

PMID- 9778809
TI  - [The persistent negative potential provoked in different structures of the rat
      brain by a single wave of spreading cortical depression].
AB  - The persistent negative potential (PNP) developed after a single wave of cortical
      spreading depression (SD) in the cortex, hippocampus, thalamus, and caudate
      nucleus. The PNP lasted for about 3-4 hours, its amplitude was 6-7 mV in the
      ipsilateral and 3-4 mV in the contralateral structures. After development of
      bilateral primary cortical SD waves the amplitudes of the respective PNP were
      summed up and reached 9-11 mV. However, after the repeated waves of cortical SD
      produced with 15-30-min intervals, the PNP level remained unchanged. We think
      that the PNP is an electrographic manifestation of the well known persistent
      vasoconstriction after a single wave of cortical SD. It seems to be related with
      reticular activation due to functional decortication.

PMID- 9778810
TI  - [The mapping of spike-wave discharges in WAG/Rij rats (a genetic strain of
      absence epilepsy)].
AB  - The electrical activity of different cortical areas was recorded in 37 WAG/Rij
      rats under conditions of chronic experiment. The typical for absence epilepsy
      spike-wave discharges occur in EEG of all the animals of the strain. The average
      amplitude distribution maps were constructed based on the recording of two main
      components of the spike-wave discharge. The most frequently occurring discharges
      of 5-9 s in duration were taken for map construction. Separate maps were
      constructed for the beginning and for the end a discharge. It was shown that at
      the beginning of a discharge the maximum of spike amplitude was localized in the
      frontal cortical area in the site of localization of the eye, vibrissa and
      chewing movement centers. At the same time, the wave was better pronounced in the
      occipital cortical areas. At the end of a discharge spike amplitude diminished
      and the cortical square over which it was manifested was cut down. On the
      contrary, at the end of a discharge were amplitude increased and the area of its
      distinct recording spread to the frontal cortical areas. The wave amplitude
      maximum was observed over the cortical areas 17. The obtained evidence suggest
      the relatively independent spatio-temporal dynamics of the two main components of
      the spike-wave discharge complex.

PMID- 9778811
TI  - [Foci of pathological activity in the human brain and their influence on the
      spatial-temporal relationships of the EEG].
AB  - EEGs of 51 patients with focal brain lesions (tumor localized in brain
      hemispheres) were analyzed. Coherence functions were calculated between the EEG
      recorded from the intact and lesioned hemispheres and three-dimensional analysis
      of the delta-wave "source" localization was conducted. The revealed delta-wave
      "sources" localized in the perifocal region of the lesioned hemisphere
      demonstrated its dynamic properties and a tendency for fluctuations. Changes in
      the delta-wave "source" pattern were correlated with the EEG coherence values
      neither in the lesioned nor in the intact hemisphere. The focus of pathological
      activity produced the changes in EEG coherence and its interhemispheric
      asymmetry. In the majority of cases (72%), the mean level of intrahemispheric
      coherence at the side ipsilateral to the pathological focus was lower than the
      normal mean level, and the mean level of EEG coherence in the intact hemisphere
      was increased.

PMID- 9778812
TI  - [A search for the sources of pathological alpha activity in the human EEG in
      limbic structure lesions].
AB  - Dependence of manifestations of EEG pathological activity on the electrode
      montage was studied in cases of brain lesions involving limbic structures by
      means of the topographic mapping and 3-d dipole source localization. The original
      program DIPVIS on the basis of BRAINLOC software allowed us to reveal the stable
      sources of lateralized pathologic alpha activity and demonstrate the discrepancy
      between its localization and the localization of the normal human alpha rhythm.
      The sources of pathological activity in question were predominantly localized in
      the mediobasal structures of the affected hemisphere in contrast to the occipital
      region of a healthy human. It was established that the topography of the cortical
      pathological activity may be determined by peculiarities of localization and,
      especially, orientation of its dipole generators. Afferent stimulation produced
      an enhancement of the pathological alpha-activity and increase in dipole source
      concentration in the mediobasal portion of the temporal lobe. The findings
      suggest that the discovered from of the alpha-rhythm reflects the reaction of
      activation of the hippocampal structures involved in the pathological process.

PMID- 9778813
TI  - [The hemispheric relationships of the human brain during the recovery of
      consciousness after a long-term coma: an EEG analysis].
AB  - Analysis of the intra- and interhemispheric EEG coherence in the dynamics of coma
      regress and its comparison with the clinical stages of postcomatose recovery
      period revealed both specific interhemispheric rearrangements of the structure of
      intercentral functional relations, which developed in parallel with the recovery
      at first of the visual, and then speech functions, and the adaptive-compensatory
      changes in activity of the regulatory systems, which provide the recovery of
      mental functions. It is emphasized that the interhemispheric EEG coherence
      asymmetry, its character and dynamics are significant for formation of
      neurophysiological mechanisms of consciousness and the course of compensatory
      processes under the extreme conditions.

PMID- 9778814
TI  - [Evoked potentials in assessing the sensory, activating and cognitive functions
      of the normal human brain and in cortical and subcortical types of vascular
      dementia].
AB  - Characteristics of the auditory EP under conditions of stimulus recognition (the
      P300 technique) and parameters of the visual "nonspecific" EP to light flash were
      studied in healthy subjects of the wide age range (18-78 years old) and patients
      with vascular dementia of different severity. It was shown that P300 parameters
      depended on age in healthy patients and on expression of cognitive dysfunction in
      demented patients. The changes were more pronounced in dementia of the cortical
      type. The P300 to nonrelevant stimulus was not age-dependent and slightly changed
      at cognitive dysfunction. Parameters of the nonspecific visual responses (the
      latency and duration--the index of homeostatic regulation) and maximal amplitude
      (reflecting the extent of activation processes) were not age-dependent and
      changed both in subcortical and cortical dementia types (increase in response
      latency and duration). In cognitive dysfunctions of subcortical origin
      homeostatic changes in the form of increase in time of homeostatic regulation and
      deterioration of stabilization of brain electrical processes were more
      pronounced.

PMID- 9778815
TI  - [The P300 component of the auditory evoked potential in the posttraumatic
      vegetative state].
AB  - The dynamic studies of P300 component of the acoustic evoked potential were
      conducted in 12 patients in posttraumatic state of the autonomic system. The
      amplitude and time parameters of P300 were analyzed, its spatial distribution
      over the cortex, and features of generation. The obtained results were compared
      with the normative data. Significant changes in P300 in comparison with the
      normal characteristics were revealed in patients with the absence of conscious
      mental activity. These changes were maximally expressed when the state of
      patients was irreversible. In case of patients' outcome from the studied state
      the amplitude-temporal and topographic response characteristics tended to
      normalization but did not reach it completely. The obtained results allow us to
      consider the P300 component as one of the most informative indices in
      consciousness recovery after severe brain injury.

PMID- 9778817
TI  - [The cortical reactions during sensory and motor activities in healthy children
      and adults and in depression patients].
AB  - Studying the visual perception by means of EP recording in the visual and motor
      cortical areas and cortical reactions during hand movements revealed resemblance
      of these reactions in children to those in patients with endogenous (cyclophrenia
      and low-progredient schizophrenia) depressive disorders. In perception, the
      latency of the early and middle EP components was reduced. An increase in
      reactivity of the right hemisphere and ipsilateral reactions were induced by the
      movement.

PMID- 9778816
TI  - [A dynamic assessment of the reaction of the human brain to radiation exposure
      (the aftermath of the accident at the Chernobyl Atomic Electric Power Station)].
AB  - The present study was aimed at the comparative assessment of electrophysiological
      and clinical data in persons (155 right-handed men) who took part in the
      Chernobyl clean-up in different periods after radiation. Dynamic evaluation of
      psychoneurological disorders revealed the growth of incidence and severity of
      cerebrovascular disturbances accompanied by the signs of organic symptoms'
      aggravation and encephalopathy in longer periods after radiation. The results of
      neuropsychological examination also showed the deterioration of patients' state
      manifested as growth of fatigue, cognitive defects, and emotional impairments.
      Analysis of the EEG parameters, including power and coherence mapping and 3-d
      dipole source localization analysis demonstrated the increasing number of
      patients with the most severe forms of EEG pathology: the "plane" type in
      combination with fast paroxysmal (beta-band) and slow forms of activity from 45%
      in 1990-92 to 63% in 1997. The "hypersynchronization" type of EEG activity was
      typical for the earlier period accompanied by the dominance of the pathological
      forms of EEG activity in mediobasal structures of the left hemisphere, and
      brainstem zones vs. diencephalon and the right hemisphere. The later period was
      characterized by decreasing coherence in symmetrical frontal and front-temporal
      areas of the left hemisphere, while in the early period the hypersynchronization
      prevailed in symmetrical central areas and in the right hemisphere. The evidence
      were obtained to a disconnection between the brain hemispheres. We suppose that
      the progressive involvement of structures of the limbic-reticular complex
      (especially, brainstem, mediobasal structures, and white matter) into the
      pathological process occurs with time in participants of clean-up of the
      Chernobyl disaster consequences.

PMID- 9778818
TI  - [Neuromonitoring: its current status and developmental outlook].
AB  - A comparative analysis of monitoring techniques in neurosurgery is presented.
      Different facets of indications and possibilities of different techniques of
      monitoring as well as appropriate ways of their application are considered. The
      promise of multimodal monitoring is justified. The requirements for the general
      neuromonitoring concept are discussed.

PMID- 9778819
TI  - [Changes in the cortical electrical activity during the formation in man of a
      visual set].
AB  - The EEG spectra were studied in 75 healthy adult patients during formation,
      actualization, and extinction of the visual set. In the group of subjects which
      had formed the stable set, the spectral power in the alpha band was higher and
      that in the delta and theta bands lower than in the group of subjects with
      unstable set. In the course of the experiment, such relationships remained
      basically the same. These findings suggest that the subjects who had the longer
      mismatch between the unconscious "internal image" and the real stimuli presented
      in a new situation (i.e., the subjects with the stable set) were closer to the
      state of physiological rest.

PMID- 9778820
TI  - Factors affecting the retention of dust mite allergen on carpet.
AB  - Carpeting is one of the most common and perhaps the most important reservoir of
      aeroallergens and other components of dust found in residential or commercial
      settings. This research evaluated factors that affect the retention of dust mite
      allergens on different types of tufted carpet commonly found in homes and
      offices. Twenty-six types of carpet were custom manufactured as part of a two
      stage factorial experiment using 182 carpet samples. Carpets differed with
      respect to fiber denier, cross-sectional shape, presence of fluorocarbon
      treatment, carpet style, pile height, and pile density. The major hypothesis
      tested was that the amount of allergen-containing dust recovered from vacuum
      samples of tufted carpet sources was dependent on micro (fiber) or macro
      (construction) retention characteristics of the carpets. Carpet samples were
      doped in a uniform and reproducible manner using an allergen-containing reference
      dust. A standardized vacuum surface sampler was used to recover dust from
      samples. Allergen was assayed using a standard, monoclonal antibody ELISA. Carpet
      surface area and presence of fluorocarbon were found to have the largest effects
      on retention and recovery of dust and allergen. Specifically, fluorocarbon
      treatment of fibers, square-hollow fiber shape, high-denier fiber, low-pile
      height in cut-pile carpets, and low-pile density in loop carpets were
      significantly associated with increased release and recovery of allergen. Results
      from this study suggest that carpet type be considered for both allergen
      avoidance and allergy and asthma risk assessment.

PMID- 9778821
TI  - A portable vapor/particle sampler.
AB  - The airborne particle and vapor phases of a volatile organic chemical (VOC) often
      coexist in the real workplace environment. Assessment of worker exposure to a VOC
      requires measuring not only the total airborne concentration but also the phase
      distribution because the deposition efficiency of the material in the respiratory
      tract will depend on the form in which it is inhaled. A prototype portable
      vapor/particle sampler (PVPS) has been designed for sampling and quantifying the
      phase distribution of volatile components in micrometer-sized airborne particles
      and coexisting gaseous phase based on differential inertia. The sampler was
      laboratory tested and validated. Tests included sampler performance assessment
      and comparison with current sampling methods for particles and organic vapors,
      i.e., glass fiber filter, charcoal sorbent tube, and diffusion monitors. The PVPS
      is a low-cost and lightweight device that can be driven by a single standard
      personal sampling pump. The mass quantities of materials collected by the sampler
      can be determined by standard analytical procedures. Combined with an appropriate
      size-selective inlet, the PVPS may be used as a personal inhalable or respirable
      volatile aerosol sampler for occupational VOC exposure assessment, especially in
      industrial, or household, spray work environments where the particle sizes are
      frequently large.

PMID- 9778822
TI  - Radon-222 and gamma ray levels associated with the collection, processing,
      transmission, and utilization of natural gas.
AB  - The natural gas industry in British Columbia was investigated for exposure to
      radioactive contaminants such as radon-222 and lead-210. Radon activity
      associated with the gathering system ranged from 7-921 Bq/m3. The pipelines to
      the processing facility contained sludge that had a mean lead-210 activity of
      0.494 Bq/g (0.379 standard deviation [SD]) and a mean radium-226 activity of
      0.417 (0.398 SD). Within the processing facility the highest levels of radon were
      associated with propane production streams, and activities as high as 4958 Bq/m3
      were found. Equipment handling these streams was also found to have a buildup of
      scale with lead-210, radium-224, and radium-226 activity. The transmission of
      salable gas to the consumer indicated a decrease in radon activity that was
      slightly lower than the estimated radon activity based on the half-life of radon,
      the distance from the production facility, and the speed of gas transmission. The
      risk of radon exposure to the worker was deemed well below the guidelines and
      would be controlled more than adequately by means of the occupational standards
      for the natural gas components. Gamma ray exposure was also well below the
      occupational standards. Radon exposure to the consumer was virtually nonexistent
      in the Vancouver region from both natural gas and propane. Although this might
      not be the case for consumers of propane closer to the production facilities, its
      contribution is likely to be minimal.

PMID- 9778823
TI  - An ergonomic characterization of work in concrete form construction.
AB  - Concrete formwork construction was identified as the area of greatest ergonomic
      risk in unionized carpentry by both managers and unionized carpenters. Ergonomic
      risks were identified and characterized using (a) 1220 randomized work samples
      from videotape, (b) 82 worker discomfort surveys, (c) on-site observation, and
      (d) labor-management focus group discussions. Results showed that carpenters
      spent over 40% of the day in a forward torso flexion posture and over one-third
      of the day working at or below knee level. Hammering was the single most
      frequently performed activity at approximately 17% of the day. The body location
      with the highest reported prevalence of symptomatic disorders was the lower back
      at 48% followed by the forearms/wrist at 37%. It was concluded that carpenters
      are exposed to significant hazards in formwork construction, and that
      opportunities exist for the implementation of ergonomic interventions.

PMID- 9778824
TI  - Improving indoor air quality through the use of continual multipoint monitoring
      of carbon dioxide and dew point.
AB  - This article summarizes an approach for improving the indoor air quality (IAQ) in
      a building by providing feedback on the performance of the ventilation system.
      The delivery of adequate quantities of ventilation to all building occupants is
      necessary for the achievement of good IAQ. Feedback on the performance includes
      information on the adequacy of ventilation provided, the effectiveness of the
      distribution of this air, the adequacy of the duration of operation of the
      ventilation system, and the identification of leakage into the return plenum,
      either of outdoor or supply air. Keeping track of ventilation system performance
      is important not only in terms of maintaining good IAQ, but also making sure that
      this system continues to perform as intended after changes in building use.
      Information on the performance of the ventilation system is achieved by means of
      an automated sampling system that draws air from multiple locations and delivers
      it to both a carbon dioxide monitor and dew point sensor. The use of single
      shared sensors facilitates calibration checks as well as helps to guarantee data
      integrity. This approach to monitoring a building's ventilation system offers the
      possibility of achieving sustainable performance of this important aspect of good
      IAQ.

PMID- 9778825
TI  - Whole-body vibration of tractor drivers during harrowing.
AB  - The seat vibration of nine tractors was investigated while drivers harrowed
      fields in eastern Finland. The vibration acceleration of the tractor driver's
      seat was measured simultaneously along three mutually perpendicular axes. The
      triaxial seat-accelerometer was used for the measurements. The vibration signals
      were amplified with charge amplifiers and recorded with an FM tape recorder. The
      samples were analyzed with a real-time analyzer. In all cases, the average
      vibration of the seat exceeded the 8-hour "fatigue-decreased proficiency
      boundary" specified in the international standard ISO 2631/1. The instantaneous
      accelerations of the most harmful one-third octave band of vibration were
      sometimes two- to threefold compared with the average.

PMID- 9778826
TI  - A shape-contrast effect for briefly presented stimuli.
AB  - When a suprathreshold visual stimulus is flashed for 60-300 ms and masked, though
      it is no longer visibly degraded, the perceived shape is vulnerable to distortion
      effects, especially when a 2nd shape is present. Specifically, when preceded by a
      flashed line, a briefly flashed circle appears to be an ellipse elongated
      perpendicular to the line. Given an appropriate stimulus onset asynchrony, this
      distortion is perceived when the 2 stimuli (approximately 4 degrees) are
      presented as far as 12 degrees apart but is not due to perception of apparent
      motion between the 2 stimuli. Additional pairs of shapes defined by taper and
      overall curvature also revealed similar nonlocal shape distortion effects. The
      test shapes always appeared to be more dissimilar to the priming shapes, a
      distortion termed a shape-contrast effect. Its properties are consistent with the
      response characteristics of the shape-tuned neurons in the inferotemporal cortex
      and may reveal the underlying dimensions of early shape encoding.

PMID- 9778827
TI  - Attentional control during visual search: the effect of irrelevant singletons.
AB  - Four experiments investigated whether a highly salient color singleton can be
      ignored during serial search. Observers searched for a target letter among
      nontarget letters and were instructed to ignore an irrelevant, highly salient
      color singleton that was either compatible or incompatible with the response to
      the target letter. The results indicate that it was possible to prevent
      attentional capture by the irrelevant singleton only when both the target and the
      distractor color were known. When either the color of the target or the color of
      the to-be-ignored singleton were varied over trials, the irrelevant singleton
      captured attention. The ability to selectively filter singleton distractors
      during serial search depends on the presence of an attentional set for a specific
      feature value of both target and distractor. In the absence of a consistently
      predictable feature value of both target and distractor, top-down control is not
      possible.

PMID- 9778828
TI  - Texture segregation and visual search: a comparison of the effects of random
      variations along irrelevant dimensions.
AB  - The effects of irrelevant variations in the color and depth of elements on
      participants' ability to detect and discriminate elements defined by a difference
      in orientation were compared. Consistent with previous research, it was found
      that there was no effect or small effects if the targets were single elements in
      visual search tasks and that there were large effects for targets defined by
      several elements defining an area in visual segmentation tasks. It is suggested
      that the reason for the discrepancy between the 2 paradigms lies in the need for
      grouping processes in segmentation experiments. This notion was examined in 3
      additional experiments that manipulated grouping processes through task demands
      and stimulus design. The data provide tentative support for this notion.

PMID- 9778829
TI  - Decomposing visual search: evidence of multiple item-specific skills.
AB  - Four experiments demonstrated that visual search can be decomposed into two
      components: one consisting of skills shared with memory search and the other
      consisting of skills not shared with memory search. A training-transfer paradigm
      was used to test for transfer from memory search to visual search and vice versa.
      When the same targets and distractors were used in training and transfer, visual
      search practice completely trained memory search, but memory search practice only
      partially trained visual search. Learning on both the shared and the private
      components of visual search benefited more from item-specific training than from
      nonspecific training. The relationship between the components and some theorized
      models of visual search are discussed, particularly in terms of prioritization
      learning.

PMID- 9778830
TI  - Preferential orienting to faces in newborns: a temporal-nasal asymmetry.
AB  - It has been proposed that newborns' preferential orienting to faces is primarily
      controlled by a subcortical mechanism. As an index of subcortical,
      extrageniculate mediation, the asymmetry between the temporal and nasal
      hemifields was exploited. In Experiment 1, under monocular viewing conditions,
      newborns were presented with a pattern that had 3 blobs in the appropriate
      locations for the eyes and the mouth or a pattern that had an inverted position
      of the blobs. Results showed that newborns preferentially oriented to the
      facelike pattern only when it was presented in the temporal hemifield. In
      Experiment 2, both patterns had the blobs in the inverted position. For one
      pattern the blobs were black, and for the other they were striped. Newborns
      preferentially oriented to the striped blobs in either hemifield. The results
      support the hypothesis that in newborns, preference for facelike patterns
      reflects the activity of a subcortical mechanism.

PMID- 9778831
TI  - Beyond the attentional blink: visual masking by object substitution.
AB  - If 2 targets are to be identified among distractors displayed in rapid sequence,
      correct identification of the 1st target hinders identification of the 2nd. To
      obtain this attentional blink (AB), the 1st target must be masked with a
      simultaneous (integration) or a delayed (interruption) mask indifferently. In 3
      experiments, it was shown that the 2nd target must also be masked, but that the
      precise form of masking is important: An AB occurs with interruption but not with
      integration masking. This nonequivalence of masking paradigms parallels that
      found in studies of masked priming, a phenomenon arguably related to the AB. The
      results are explained by a revised 2-stage model (M. M. Chun & M. C. Potter,
      1995).

PMID- 9778833
TI  - Your eyes only? A test of interactive influence in the processing of facial
      features.
AB  - The holistic hypothesis in face processing was tested in 3 experiments. Holistic
      processing was conceptualized as interactive influence of facial features on the
      perceptual representation of faces. In Experiment 1, 3 facial features (eye
      distance, width of nose, size of mouth) were varied on 3 values per feature.
      Photographs and blurred versions were used. Participants assigned each stimulus
      face to 1 of 2 target faces according to similarity. The data were evaluated by
      the logit model that provides a direct test of interactive influence of the
      features on participants' performance. The interactive-processing hypothesis was
      not confirmed. The results were replicated in Experiment 2, in which 2 features
      with 5 values each were used and data of individual participants were evaluated,
      and in Experiment 3, in which a reduced presentation time of 250 ms was used. It
      is concluded that facial features are processed and represented independently.

PMID- 9778832
TI  - Inhibition of return to successively stimulated locations in a sequential visual
      search paradigm.
AB  - The inhibition of return (IOR) effect refers to a slowing in response time for a
      target that appears at a previously attended location. Many investigators have
      speculated that IOR's inherent ecological validity may be to ensure an efficient
      search of a complex environment by creating a bias against returning to locations
      that have already been investigated. Unfortunately, this intriguing idea has
      lacked compelling empirical support. The current study addressed this issue. It
      was shown that in a novel visual search task, the IOR could dwell at a minimum of
      3 spatially noncontiguous locations. These data suggest that IOR may serve as an
      important mechanism for facilitating visual search in complex environments, by
      inhibiting attention from returning to previously inspected locations.

PMID- 9778834
TI  - On the temporal relations between memory scanning and response preparation.
AB  - Three experiments were conducted to investigate whether response processes can
      start before memory scanning has finished when both are required in the same
      task. In Experiment 1 the color of a stimulus letter determined which hand might
      respond, and the letter's memory set membership determined whether that response
      should be made or withheld. Electrophysiological data suggested that lateralized
      response preparation was not initiated until memory scanning finished. Experiment
      2 replicated these results with a consistent stimulus-response mapping to make
      the scanning process easier. Experiment 3 tested for earlier response priming
      with a probe reaction time paradigm, and the results suggested that color
      information can be used to activate a response before memory scanning is
      finished. The results of Experiments 1-3 suggest that interference between memory
      scanning and response preparation precludes the concurrent operation of these
      processes.

PMID- 9778835
TI  - Category superiority effects and the processing of auditory images.
AB  - Music and information appear to be processed by means of the phonological loop,
      as opposed to the visuospatial sketchpad, in working memory. Is this also true of
      memory for nonverbal, nonmusical auditory images, such as the characteristic
      sounds made by objects? In the present study, university students were presented
      with equivalent verbal stimuli, nonsemantic auditory stimuli, or pictorial
      stimuli, by category or in random order. Significant category superiority effects
      (CSEs) were obtained for both verbal and auditory stimuli, but not for pictorial
      stimuli, consistent with the expectation of phonological loop processing.
      However, absolute levels of recall for auditory stimuli were significantly higher
      than for verbal stimuli and did not differ from the levels observed for pictures,
      suggesting a somewhat intermediate character of processing for nonverbal,
      nonmusical auditory information.

PMID- 9778836
TI  - The effect of depression in an animal model on 5'-ectonucleotidase, antibody
      production, and tissue ascorbate stores.
AB  - The learned helplessness model of depression in rats was tested. It was
      hypothesized that 5'-ectonucleotidase (NT), ascorbate, and antibody to sheeps'
      red blood cells (SRBC) are significantly reduced in rats who experienced
      uncontrollable shock, compared with rats who did not receive shock or could
      control it. During a learned-helplessness manipulation, antibody response to SRBC
      and NT values were unaffected. However, tissue ascorbate stores fell
      significantly, by 20-30%. The lack of effects on antibody responses and NT are
      discussed n terms of the acute nature of the stressor used in this model, as
      opposed to the more chronic stressors that have occurred in the human model.

PMID- 9778837
TI  - Hypermnesia for prose.
AB  - Hypermnesia is an improvement in memory that occurs with repeated testing. In the
      present experiment, hypermnesia was examined with prose materials. Participants
      were presented with either a fairy tale or an expository passage, followed by 3
      free-recall tests. Participants used 1 of 2 encoding strategies (the relational
      or item-specific processing conditions) to process the material, or they simply
      read the material (the read-only condition). Recall performance improved across
      the 3 tests in the relational and item-specific processing conditions. No
      improvement was found in the read-only condition.

PMID- 9778838
TI  - Institutional Review Board issues related to special populations.
AB  - The present article begins with an introduction to the role of Institutional
      Review Boards (IRBs) in research activities in general and proceeds to issues
      IRBs face with relation to special populations, including children and terminally
      ill individuals, as well as developmentally disabled and cognitively impaired
      persons. A historical overview of research with these special populations is
      included, and the report concludes with a real-world example of how IRB-related
      issues with developmentally disabled and cognitively impaired individuals are
      discussed and resolved.

PMID- 9778839
TI  - Self-reported impulsivity is correlated with laboratory-measured escape behavior.
AB  - Aggression has been previously correlated with impulsive personality. In the
      present study, Barratt Impulsiveness Scale (BIS) scores of 40 male controls aged
      15-40 years were related to the frequency of free-operant aggressive and escape
      responses toward a fictitious antagonist. Participants earned "points" worth
      money with repeated button presses on a fixed-ratio schedule and were provoked by
      the periodic subtraction of a point. These subtractions were blamed on the
      behavior of a (fictitious) other participant, and aggressive responses (presses
      of a separate button) were defined as those emitted by the participant with an
      intent to subtract earnings from the other (fictitious) participant. BIS scores
      were not correlated with frequency of point-subtracting (aggressive) responses to
      the point subtractions, but they were correlated with the frequency of escape
      responses on a third button, which the participant was told would protect his
      points from subtraction for an unspecified period of time. These results suggest
      that among normal controls, impulsivity might be characterized by some
      sensitivity to aversive stimuli.

PMID- 9778840
TI  - The properties of one: facial memory and the isolation effect.
AB  - In an experiment testing the extension of the von Restorff/isolation effect to
      feature recognition, observers viewed a study set of 20 faces with 0, 1, 2, or 4
      distinctive stimuli on each face. In Experiments 1 and 2, the stimuli were black
      spots (simple, distinctive stimuli), and in Experiments 3 and 4 they were
      inverted es (complex, distinctive stimuli). Observers then viewed a test set
      containing 20 study-set and 20 distractor faces. In 2 of the experiments (1 & 3),
      the test sets contained the same distinctive stimuli as the corresponding study
      set; in the other 2 experiments (2 & 4), the test sets had no distinctive
      stimuli. In Experiments 1 and 2, faces with 1 spot on them in the study/learning
      phase were recognized significantly more frequently than those that had 0, 2, or
      4 spots. That this one effect was still present when there were no spots on the
      faces in the test set demonstrates that it is an encoding phenomenon rather than
      a recall phenomenon. As predicted, that result was not replicated when inverted
      es were used (Experiments 3 and 4).

PMID- 9778841
TI  - Desktop X-ray microscopy and microtomography.
AB  - Recent developments in X-ray microtomography have made it possible to miniaturize
      a CT scanner into a versatile and cost-effective desktop system that fits into
      any laboratory environment. The possibilities of the technique are demonstrated
      for a range of applications. It is also shown how an existing scanning electron
      microscope with an X-ray detector can, with a specially developed attachment, be
      transformed into an X-ray microscope and microtomograph.

PMID- 9778842
TI  - Energy-filtered cryotransmission electron microscopy of liposomes prepared from
      human stratum corneum lipids.
AB  - We used cryo-TEM to examine the morphology of vesicles formed from lipids of the
      human stratum corneum (hSC). Human stratum corneum lipid liposomes (hSCLLs) were
      prepared in buffer at various pH values, using different preparation methods
      (film method, extrusion, ultrasonication, detergent dialysis). The morphology of
      hSCLLs at pH 7.4 differed markedly from that of liposomes formed by
      phospholipids, showing folds, stacks and membrane thickening. At pH 5.0,
      corresponding to natural conditions at the skin surface, membrane structures are
      essentially the same as those prepared at pH 7.4. Sharp edges in hSCLLs,
      branching membranes and stable membrane stacks were explained by the presence of
      ceramides, the major components and structural elements of human stratum corneum
      lipids (hSCLs). Thickened areas in the membranes may be caused by the local
      accumulation of triacylglycerols and cholesterol esters in the hydrophobic
      interior of the bilayer.

PMID- 9778844
TI  - Conservation of gene structure and activity in the regulation of reproductive
      organ development of conifers and angiosperms.
AB  - The Norway spruce (Picea abies) gene DAL2 shows distinct structural similarities
      to angiosperm MADS-box genes which act in the control of the development of the
      sexual organs of the flower. Transcription of DAL2 is restricted to the
      reproductive organs, the unisexual cones, of Norway spruce. In this paper we show
      that DAL2 in the compound female cone is exclusively expressed in the developing
      ovule-bearing organ, the ovuliferous scale. When expressed constitutively in
      transgenic Arabidopsis the gene causes developmental alterations very similar to
      those observed in plants ectopically expressing the Arabidopsis gene AGAMOUS and
      the closely related Brassica napus gene BAG1. These alterations include homeotic
      transformations of floral organs. On the basis of these data and analysis of the
      phylogeny of the plant MADS-box gene family, we propose that DAL2 acts to control
      reproductive organ development in spruce. We also propose that DAL2 shares a
      common origin with AGAMOUS and related genes from other angiosperms, in an
      ancestral MADS-box gene that was active in the control of ontogeny of ovule
      bearing organs in the unknown last common ancestor of conifers and angiosperms.

PMID- 9778845
TI  - Characterization of an AGAMOUS homologue from the conifer black spruce (Picea
      mariana) that produces floral homeotic conversions when expressed in Arabidopsis.
AB  - Advances in elucidating the molecular processes controlling flower initiation and
      development have provided unique opportunities to investigate the developmental
      genetics of non-flowering plants. In addition to providing insights into the
      evolutionary aspects of seed plants, identification of genes regulating
      reproductive organ development in gymnosperms could help determine the level of
      homology with current models of flower induction and floral organ identity. Based
      upon this, we have searched for putative developmental regulators in conifers
      with amino acid sequence homology to MADS-box genes. PCR cloning using degenerate
      primers targeted to the MADS-box domain revealed the presence of over 27 MADS-box
      genes within black spruce (Picea mariana), including several with extensive
      homology to either AP1 or AGAMOUS, both known to regulate flower development in
      Arabidopsis. This indicates that like angiosperms, conifers contain a large and
      diverse MADS-box gene family that probably includes regulators of reproductive
      organ development. Confirmation of this was provided by the characterization of
      an AGAMOUS-like cDNA clone called SAG1, whose conservation of intron position and
      tissue-specific expression within reproductive organs indicate that it is a
      homologue of AGAMOUS. Functional homology with AGAMOUS was demonstrated by the
      ability of SAG1 to produce homeotic conversions of sepals to carpels and petals
      to stamens when ectopically expressed in transgenic Arabidopsis. This suggests
      that some of the genetic pathways controlling flower and cone development are
      homologous, and antedate the 300-million-year-old divergence of angiosperms and
      gymnosperms.

PMID- 9778846
TI  - Higher plants possess two structurally different poly(ADP-ribose) polymerases.
AB  - One of the immediate reactions of the mammalian cell to many environmental
      stresses is a massive synthesis of poly(ADP-ribose), catalyzed by poly(ADP
      ribose) polymerase (PARP). Most of the biological functions attributed to PARP
      are inferred from experimentation with mammalian cells. In plants, the biology of
      PARP may be more complicated and diverse than was previously thought. Two
      poly(ADP-ribose) polymerase homologues were found in plants, the classical Zn
      finger-containing polymerase (ZAP) and the structurally non-classical PARP
      proteins (APP and NAP), which lack the characteristic N-terminal Zn-finger
      domain. By enzymatic and cytological experiments the recombinant APP protein was
      shown to be located in the nucleus and to possess DNA-dependent poly(ADP-ribose)
      polymerase activity in yeast. The nuclear localization was further confirmed by
      the analysis of transgenic tobacco plants that expressed a translational gene
      fusion between APP and the bacterial beta-glucuronidase. The app promoter was
      transcriptionally up-regulated in cells pre-determined to die because of
      deficiency in a DNA ligase I.

PMID- 9778847
TI  - Characterization of a tobacco epoxide hydrolase gene induced during the
      resistance response to TMV.
AB  - A clone encoding a putative soluble epoxide hydrolase (EH-1), an enzyme which
      converts epoxides to diols, was isolated by differential screening of a cDNA
      library prepared from tobacco mosaic virus (TMV)-infected tobacco leaves. To
      confirm that EH-1 encodes an epoxide hydrolase, the recombinant EH-1 protein
      produced in bacteria was shown to have high epoxide hydrolase activity in vitro.
      Infection of resistant but not susceptible tobacco cultivars induced the
      accumulation of EH-1 transcripts in both the inoculated and uninoculated,
      systemic leaves. EH-1 expression was also induced in the inoculated and systemic
      tissues of TMV-infected NahG plants, which are unable to accumulate salicylic
      acid (SA). However, EH-1 expression in the inoculated leaves of NahG plants was
      delayed, whilst in the systemic leaves the induction was both later and weaker,
      compared to that observed in wild-type plants. Furthermore, exogenously applied
      SA or its functional analog 2,6-dichloroisonicotinic acid (INA) caused a rapid
      and transient accumulation of EH-1 transcripts, whereas an inactive SA analog did
      not. Thus, the induction of EH-1 gene expression appears to be regulated by both
      SA-independent and SA-dependent pathways. Since EH-1 was expressed only in TMV
      resistant tobacco after infection, and the encoded enzyme is thought to help
      metabolize toxic compounds, we propose that EH-1 may play a role in protection
      from oxidative damage associated with defense responses. It may also play a role
      in generating signals for activation of certain defense responses.

PMID- 9778849
TI  - Allene oxide synthase: a major control point in Arabidopsis thaliana octadecanoid
      signalling.
AB  - The analysis of allene oxide synthase (AOS) mRNA levels, of AOS polypeptide
      levels and specific enzymatic activities, as well as the quantitative
      determination of the levels of the octadecanoids cis-12-oxophytodienoic acid (cis
      OPDA) and JA following a number of treatments, has shown that AOS is a regulatory
      site in octadecanoid biosynthesis in A. thaliana. AOS activity, mRNA and
      polypeptide levels are increased in wounded leaves locally and systemically. The
      methyl esters of OPDA or JA (OPDAME, JAME) and coronatine, are strong inducers of
      AOS mRNA, polypeptide and enzymatic activity. Ethephon also induces AOS activity.
      Salicylic acid (SA) was an inducer of AOS activity while abscisic acid (ABA) had
      no effect. At the level of the octadecanoids, the consequences of induction of
      AOS by the different inducers were distinctly different, depending on the nature
      of the inducer. Wounding led to a strong, bi-phasic accumulation of JA in wounded
      leaves and to a less pronounced increase in JA-levels in systemic leaves. Levels
      of OPDA changed very little in wounded leaves and remained constant or even
      declined in systemic leaves. Ethephon treatment resulted in a strong, transient
      increase in JA-levels kinetically coinciding with the second, more pronounced
      peak in wound-induced JA. In SA-treated leaves, the level of cis-OPDA increased
      throughout the experimental period while there was no effect on JA levels during
      the first 24 h following treatment and only a slight accumulation after 48 h.
      Clearly, mechanisms in addition to regulating substrate (LA) availability and the
      regulation of AOS accumulation control the output of the octadecanoid pathway.

PMID- 9778848
TI  - UV-B-induced photomorphogenesis in Arabidopsis thaliana.
AB  - Relatively little is known about the types of photomorphogenic responses and
      signal transduction pathways that plants employ in response to ultraviolet-B (UV
      B, 290-320 nm) radiation. In wild-type Arabidopsis seedlings, hypocotyl growth
      inhibition and cotyledon expansion were both reproducibly promoted by continuous
      UV-B. The fluence rate response of hypocotyl elongation was examined and showed a
      biphasic response. Whereas photomorphogenic responses were observed at low doses,
      higher fluences resulted in damage symptoms. In support of our theory that
      photomorphogenesis, but not damage, occurs at low doses of UV-B, photomorphogenic
      responses of UV-B sensitive mutants were indistinguishable from wild-type plants
      at the low dose. This allowed us to examine UV-B-induced photomorphogenesis in
      photoreceptor deficient plants and constitutive photomorphogenic mutants. The
      cry1 cryptochrome structural gene mutant, and phytochrome deficient hy1, phyA and
      phyB mutant seedlings resembled wild-type seedlings, while phyA/phyB double
      mutants were less sensitive to the photomorphogenic effects of UV-B. These
      results suggest that either phyA or phyB is required for UV-B-induced
      photomorphogenesis. The constitutive photomorphogenic mutants cop1 and det1 did
      not show significant inhibition of hypocotyl growth in response to UV-B, while
      det2 was strongly affected by UV-B irradiation. This suggests that COP1 and DET1
      work downstream of the UV-B signaling pathway.

PMID- 9778850
TI  - The 3' untranslated region of a rice alpha-amylase gene mediates sugar-dependent
      abundance of mRNA.
AB  - A decrease in transcript stability is one of the important mechanisms that
      control the sugar repression of alpha-amylase gene expression in rice suspension
      cells. In this study, we investigated the function of the 3' untranslated region
      (3'UTR) of a rice alpha-amylase gene, alpha Amy3, in relation to sugar-dependent
      accumulation of mRNA. By examining the transient expression of chimeric genes in
      rice protoplasts, we were able to demonstrate that the alpha Amy3 3'UTR mediated
      the sugar-dependent repression of fused heterologous gene expression. The same
      kinetics of accumulation of alpha Amy3 mRNA and reporter mRNA carrying the alpha
      Amy3 3'UTR in response to glucose deprivation were observed, suggesting that the
      alpha Amy3 3'UTR is sufficient, and probably the major determinant for
      controlling the abundance of these transcripts. Functional analysis of two
      subdomains of alpha Amy3 3'UTR by insertion into a sugar-inducible chimeric gene
      confirmed their roles in sugar repressibility. The regulatory sequences in the
      alpha Amy3 3'UTR may act as potent determinants of mRNA stability in response to
      sugar availability. This finding has important implications for studying the
      regulatory mechanism of sugar repression in eukaryotes.

PMID- 9778851
TI  - High-efficiency cloning of Arabidopsis full-length cDNA by biotinylated CAP
      trapper.
AB  - Full-length cDNAs are essential for functional analysis of plant genes. We
      constructed high-content, full-length cDNA libraries from Arabidopsis thaliana
      plants based on chemical introduction of a biotin group into the diol residue of
      the CAP structure of eukaryotic mRNA, followed by RNase I treatment, to select
      full-length cDNA. More than 90% of the total clones obtained were of full length;
      recombinant clones were obtained with high efficiency (2.2 x 10(6)/9 micrograms
      starting mRNA). Sequence analysis of 111 randomly picked clones indicated that 32
      isolated cDNA groups were derived from novel genes in the A. thaliana genome.

PMID- 9778852
TI  - An ordered Arabidopsis thaliana mitochondrial cDNA library on high-density
      filters allows rapid systematic analysis of plant gene expression: a pilot study.
AB  - The availability of the complete sequence of a genome allows a systematic
      analysis of its expression. Gene-specific variations of transcription levels and
      phenomena such as transcript processing and RNA editing require large numbers of
      clones to be examined. For the completely sequenced mitochondrial genome of
      Arabidopsis thaliana we adapted robot technology to identify and characterize
      expressed genes. A cDNA library of about 50,000 clones was constructed, robot
      ordered into 384-well microtitre plates and spotted onto high-density filter
      membranes. These filters permit the isolation of large numbers of specific cDNA
      clones in a single hybridization step. The cox1, cox2 and cox3 genes were used to
      evaluate the feasibility and efficiency of this approach. A cluster of RNA
      editing sites observed outside the cox3 coding region identifies a novel reading
      frame orf95 in higher plants with significant similarity to a subunit of
      respiratory chain complex II.

PMID- 9778853
TI  - The development of a scale to measure concepts of schizophrenia: experience among
      Brazilian psychiatrists.
AB  - INTRODUCTION: Among psychiatric disorders schizophrenia is often said to be the
      condition with the most disputed definition. The Bleulerian and Schneiderian
      approaches have given rise to diagnostic formulations that have varied with time
      and place. Controversies over the concept of schizophrenia were examined within
      European/North American settings in the early 1970s but little has since been
      reported on the views of psychiatrists in developing countries. In Brazil both
      concepts are referred to in the literature. A scale was developed to measure
      adherence to Bleulerian and Schneiderian concepts among psychiatrists working in
      S. Paulo. METHODOLOGY: A self-reported questionnaire comprising seventeen visual
      analogue-scale statements related to Bleulerian and Schneiderian definitions of
      Schizophrenia, plus sociodemographic and training characteristics, was
      distributed to a non-randomised sample of 150 psychiatrists. The two sub-scales
      were assessed by psychometric methods for internal consistency, sub-scale
      structure and test-retest reliability. Items selected according to internal
      consistency were examined by a two-factor model exploratory factor analysis.
      Intraclass correlation coefficients described the stability of the scale.
      RESULTS: Replies were received from 117 psychiatrists (mean age 36 (SD 7.9)), 74%
      of whom were made and 26% female. The Schneiderian scale showed better overall
      internal consistency than the Bleulerian scale. Intra-class correlation
      coefficients for test-retest comparisons were between 0.5 and 0.7 for
      Schneiderian items and 0.2 and 0.7 for Bleulerian items. There was no negative
      association between Bleulerian and Schneiderian scale scores, suggesting that
      respondents may hold both concepts. Place of training was significantly
      associated with the respondent's opinion; disagreement with a Bleulerian
      standpoint predominated for those trained at the University of S. Paulo.
      CONCLUSIONS: The less satisfactory reliability for the Bleulerian sub-scale
      limits confidence in the whole scale but on the other hand this questionnaire
      contributes to the understanding of the controversy over Bleulerian and
      Schneiderian models for conceptualisation of schizophrenia, the former requiring
      more inference and therefore being prone to unreliability.

PMID- 9778855
TI  - [Small for gestational age: risk factor for neonatal mortality].
AB  - INTRODUCTION: Variables of birth certificates were analysed as risk factors of
      SGA (Small for Gestational Age) infantis, and with a view to discovering if
      retarded intra-uterine growth was a risk factor neonatal mortality. MATERIAL AND
      METHOD: Data were obtained directly from 11 hospital medical records. A cohort of
      2.251 hospital live births was obtained. Linkage of the death and birth
      certificates was undertaken to identify the neonatal deaths. The study was
      carried out in Santo Andre county in the S. Paulo Metropolitan area in the period
      from 1/1 to 30/6/1992. RESULTS: There were 4.3% of SGA live births. A higher
      statistically significant proportion of SGA was found in pre-term and post-term
      live births, among live births of mothers with 35 years of age and over and in
      those whose mothers had less than complete primary education. The SGA live births
      showed a higher risk of neonatal death, even when allowing for gestational age.
      CONCLUSIONS: In areas where there is a low proportion of low birthweight, the
      presence of retarded intra-uterine growth may be an important risk factor to pre
      term live births, due to the association between the pre-term and SGA. It would
      be easier to evaluate signs of retarded intra-uterine growth in the live birth
      population, if the gestational age data were registered, on the birth certificate
      in weeks.

PMID- 9778854
TI  - [Risk factors for perinatal mortality in Pelotas, a southern city of Brazil,
      1993].
AB  - INTRODUCTION: Although there was a considerable reduction in infant mortality in
      Pelotas, Rio Grande do Sul in the last decade, its perinatal causes were reduced
      only by 28%. The associated factors of these causes were analysed. MATERIAL AND
      METHOD: All hospital births and perinatal deaths were assessed by daily visits to
      all the maternity hospitals in the city, throughout 1993 and including the first
      week of 1994. RESULTS: The perinatal mortality rate was 22.1 per thousand births.
      The multivariate analysis showed the following risk factors: low socioeconomic
      level, male sex and maternal age above 35 years. Among multigravidae women, the
      fetal mortality rate was significantly increased for mothers with a previously
      low birthweight and a previous stillbirth. For early neonatal mortality the risk
      was significantly increased by a smaller number of antenatal visits than 5 and
      low birthweight. CONCLUSIONS: Main risk factors for perinatal mortality: low
      socioeconomic level, maternal age above 35 years and male sex. For early neonatal
      mortality the risk was significantly increased by a smaller number of antenatal
      visits than 5 and low birthweight.

PMID- 9778856
TI  - [Incidence and duration of breast-feeding by type of delivery: a longitudinal
      study in southeastern of Brazil].
AB  - OBJECTIVE: To compare the incidence of breastfeeding according to type of
      delivery. METHODOLOGY: Population-based cohort study of 655 children born in 1993
      and followed up during the first three months of life through home visits.
      RESULTS: Breastfeeding duration was similar among babies born either by vaginal
      delivery or by emergency cesarean section. Babies born by elective cesarean
      section, however, presented a three times higher risk of stopping breastfeeding
      in the first month of life, after adjusting for possible confounding factors
      (odds ratio = 3.09; 95% CI 1.3-7.2). The increased risk did not persist into the
      third month of life. CONCLUSIONS: It is recommended that health services pay
      special attention, in the promotion of breastfeeding, to babies born by elective
      cesarean section, as a way to avoid early weaning.

PMID- 9778857
TI  - [Geographical distribution of dengue and socioeconomic factors in an urban
      locality in southeastern Brazil].
AB  - INTRODUCTION: The incidence of dengue (serum type I) in the city of S. Jose do
      Rio Preto during an epidemic which occurred in the first semester of 1995 is
      analyzed in terms of geographical areas defined by socioeconomic variables.
      MATERIAL AND METHOD: The epidemiological method of analysis is the "ecological
      study" type. To calculate the coefficient of incidence of dengue, all cases both
      confirmed and reported between January and July, 1995 are considered. The
      environmental units are defined according to socioeconomic variables based on the
      IBGE (Brazilian Institute of Geography and Statistics) Census of 1991, through
      cluster analysis. The linear correlation coefficient between coefficient of
      incidence and environmental variables is also calculated. RESULTS AND DISCUSSION:
      Three distinct environmental units are identified and described on the basis of
      both economic and educational level. The coefficient of incidence of dengue
      varied in accordance with the environmental unit: in the unit of low standard the
      coefficient was 2.7 times greater than that of the unit of highest standard,
      showing that in these units the determining factors of dengue have a
      differentiating effect. The roles of some of the determining factors such as
      population density, basic sanitary services and vector density are discussed. The
      importance of this study for the control of dengue is also emphasized.

PMID- 9778858
TI  - [Diabetes as primary or associated cause of death in the state of Sao Paulo,
      Brazil, 1992].
AB  - INTRODUCTION: Analysis of mortality data are usually performed with reference to
      the underlying cause of death. The importance of diabetes as a cause of death is
      always underestimated, because diabetics generally die from chronic complications
      of the disease, these being considered as the underlying cause of the death. To
      attenuate this problem, mortality data should be analyzed on the basis of all the
      causes listed on the death certificate. Frequency of references to diabetes on
      death certificates and the principal associated causes were evaluated as a
      contribution to the solution of this problem. METHODOLOGY: Specific death rates
      and proportional mortality by diabetes, as underlying or associated cause, were
      calculated on the basis of information derived from death certificates by the
      ACME program (Automated Classification of Medical Entities), for the State of S.
      Paulo, in 1992. RESULTS AND CONCLUSIONS: Of a total of 202,141 deaths, diabetes
      was mentioned in 13,786 (6.8%) and as being the underlying cause in 5,305(2.6%).
      The proportion was higher for women than men (10.1 vs. 4.6% as mentioned, and 6.1
      vs 2.9% as underlying cause). Among deaths with a mention of diabetes on the
      certificate, the main underlying causes were: diabetes (38.5%), cardiovascular
      (37.2%) and respiratory (8.5%) diseases, and neoplasias (4.8%). When diabetes was
      the underlying cause, the main associated causes were: cardiovascular (42.2%),
      respiratory (10.7%) and genitourinary (10.1%) diseases. When diabetes was an
      associated cause, the main underlying causes were: cardiovascular (60.5%) and
      respiratory (13.8%) diseases, and neoplasias (7.9%). In spite of the limitation
      of the data from death certificates, it is possible to observe the importance of
      diabetes as cause of death, reflecting its magnitude as a health problem. Also,
      the analysis by multiple causes of deaths gives an idea of the morbidity profile
      associated with diabetes at the time of death, showing the importance of the
      group of cardiovascular diseases.

PMID- 9778859
TI  - [Smoking associated with alcoholism: introduction to the major human
      dependencies].
AB  - OBJECTIVE: To establish the existence of an association between smoking and
      alcoholism in a general population sample and to compare two samples of
      alcoholics and non alcoholics matched by age and sex. MATERIAL AND METHOD: Health
      Teaching Unit Murialdo-State Health Department-RS-Brazil in a limited area of
      65,000 predicted population a cross-sectional study was undertaken in which
      adults of 35 y.o. or more were sampled. Of this sample, the alcoholics were
      selected by applying the CAGE Scale. A non alcoholic random sample was compared
      with the alcoholic one. It was identified 129 alcoholics among 1,387 adults of 35
      y.o. or more. From the general list of adults a random sample of 129 non
      alcoholics were selected and matched to the alcoholics by age and sex. Both
      groups were compared. Data were obtained from a 19 item questionnaire. Answers to
      generic questions were obtained from all family members, such as: income and
      smoking habit. Specific data were obtained from the interviewed person of 35 y.o.
      or more, such as: schooling grade, occupation, diseases and respiratory symptoms,
      smoking habit, Peak Expiratory Flow and alcoholism. RESULTS: Of 129 alcoholics,
      109 (84.5%) were male and 20 (15.5%) were female. The smoking prevalence among
      alcoholics (67%) was greater than among non alcoholics (43%) (p < .002). The kind
      of occupation distinguished both groups. Among alcoholics unemployment and
      elementary levels of occupation are more usual while among the abstemious
      intermediate and superior levels are more frequent (p < .003). The family as well
      as the personal income are higher among the abstemious (p < .001). There is an
      increased non significant number of non whites, illiterate people and family
      smokers among the alcoholics (p < .06). The tendency to start smoking earlier in
      life and to smoke more cigarettes for a longer period of time was noticed among
      alcoholics. CONCLUSIONS: There is a statistical association between smoking and
      alcoholism in the sample studied. Alcoholism in this sample is more prevalent
      among people who fulfil the following conditions: smokers, low income,
      rudimentary cultural and professional levels.

PMID- 9778861
TI  - [Molluscacidal activity of Paraiso (Melia azedarach L.) (Meliaceae) on Lymnaea
      cubensis, host snail of fascioliasis].
AB  - INTRODUCTION: Fasciolosis is a source of serious economic loss in various regions
      of Brazil and when control measures of its host (molluscs) are not taken under
      favorable ecological conditions, isolated cases of human Fasciolosis may occur.
      Among the alternative measures for its control is the use of vegetable extracts
      and the purpose of this project is the assessment of the use of juice extracted
      from the fruit and seeds of the Paraiso plant (Melia azedarach L.) in the control
      of Lymnaea cubensis, the main vector of Fasciolosis in Cuba. MATERIAL AND METHOD:
      Various concentrations of the juice extracted from the Paraiso fruit (Melia
      azedarach L.) were tested to determine the average and maximum lethal doses (DL50
      and DL90' respectively) used in a computerized PROBIT-LOG program. Seven
      experimental series were undertaken, 72 molluscs being used in each of them.
      Three groups of ten molluscs were tested to determine the effect on cardiac
      frequency, two of them being treated with CL50 = 0.88627 and CL90 = 1.7641,
      respectively, the third being used as control. RESULTS AND CONCLUSIONS: A
      considerable effect of both doses on the cardiac frequency of the mollusc studied
      was observed. The results were encouraging, for they demonstrated the potential
      use of this plant in the control of undesirable molluscs.

PMID- 9778860
TI  - [Costs of interventions for patients with chronic renal disease].
AB  - INTRODUCTION: The results of a study which identified the cost of health
      interventions in the management of patients with chronic renal disease are
      presented. MATERIAL AND METHOD: The costing method was based on a consensus
      technique and the instrumentation of case management through the identification
      of the materials used and functions of production for the demand of each service
      solicited. The interventions included: peritoneal dialysis, hemodialysis, and
      renal transplant. RESULTS: The cost per event in U.S. dollars was $3.71, $57.95,
      and $8,778.32, respectively. The annual cost of case management was: Peritoneal
      Dialysis $5,643.07, Hemodialysis $9,631.60 and renal transplant $3,021.67.
      CONCLUSIONS: The information generated from the costs of the events differed
      considerably from the information that was generated by the annual cost of case
      management. These differences are significant for the design and evaluation of
      patterns for allocating resources.

PMID- 9778862
TI  - [Method of simulation and choice of factors in the analysis of principal
      components].
AB  - OBJECTIVE: There are many methods to determine how many components should be
      retained in principal components analysis. This choice can be made on the basis
      of arbitrary (Kaiser) or subjective (Interpretable factors) criteria. This work
      presents the simulation criteria of Lebart e Dreyfus. The method create a matrix
      of randomized numbers and a principal component analysis is performed on the
      basis of this matrix. The components extracted from this data represent the cut
      off values. Those that exceed this cut off value should be retained. As an
      example, a principal component analysis is performed with the Hamilton depression
      rating scale (17 items) on a sample of 130 subjects. RESULTS AND CONCLUSION: The
      Simulation method is compared with the Kaiser method and is shown that the
      Simulation method maintains the components clinically significant.

PMID- 9778863
TI  - The impact of living on the streets on latency children's friendships.
AB  - OBJECTIVE: This is a study to evaluate friendships in latency street boys of
      Porto Alegre, RGS, Brazil. METHODS: A sample of 30 latency street boys was
      compared with a sample of 51 latency boys living with their low income families,
      using the Cornell Interview of Peers and Friends (CIPF). RESULTS: The two groups
      had a significantly different CIPF global scores, and the boys of the street
      group had the highest mean score. Also, boys of the street had significantly
      lower developmental appropriateness, self-esteem and social skills scores than
      boys living with a family. CONCLUSIONS: The urgent need for intervention street
      children, especially on boys of the street, is emphasized.

PMID- 9778864
TI  - [Recommended vaccines and immunoglobulins for immunocompromised patients].
AB  - A revision of the literature was made as to the recommendations given for the use
      of vaccines and immune globulins in persons who presented total or partial
      immunodeficiency, mainly related to the nineties. The analysis of 75 references
      led to the following principal conclusions: the vaccines containing living agents
      are generally inappropriate for persons who present conditions which determine
      serious immunodeficiency; the vaccines which contain dead agents or only
      antigenic fractions, despite their being less immunogenic and conferring lower
      rates of protection to severely immunocompromised persons as compared to normal
      persons, are safe and should be administered to them. Immunocompromised patients
      should receive immune globulins for the same indications and in the same doses as
      immunocompetent persons, with the exception of immune globulin to prevent
      measles, as recommended in a dosage of 0.5 mL/Kg for immunodeficients (15 mL,
      maximum).

PMID- 9778865
TI  - [Preterm infants: an update on human milk fortifiers].

PMID- 9778866
TI  - [Treatment of atrial fibrillation: a persistent dilemma].
AB  - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia.
      Increased life expectancy will result in a higher prevalence of AF. Treatment of
      AF constitutes a persistent medical dilemma. Different multicenter trials have
      confirmed that oral anticoagulant therapy is the best choice for the prevention
      of systemic embolism. It must be recognized, however, that the incidence of
      systemic embolism in patients with AF varies according to the presence and type
      of underlying heart disease. Advanced age increases the risk of emboli in
      patients with AF. At the same time, older patients have a higher risk of
      hemorrhage when treated with oral anticoagulants. Thus, careful titrated
      individual oral anticoagulant therapy targeted to a safe and effective INR must
      be considered in patients with AF. Another dilemma in AF patients is the
      convenience of restoring sinus rhythm and indicating permanent antiarrhythmic
      therapy versus the alternative of heart rate control plus oral anticoagulants.
      Several multicenter trials now in progress have addressed this issue and most
      likely will answer these questions. Identification of patients with paroxysmal AF
      and risk of systemic embolism constitutes another dilemma, since only a small
      proportion of these patients evolve to chronic arrhythmia. Advanced age, history
      of hypertension and left atrial enlargement in 2D Echo are well recognized risk
      factors for embolism in patients with non valvular paroxysmal AF. A history of
      previous embolism constitutes another risk factor and supports the hypothesis
      that AF may activate systemic coagulation factors and left atrial thrombus
      formation in some patients.

PMID- 9778867
TI  - [Ambulatory geriatric assessment of 2116 in poor elderly].
AB  - BACKGROUND: Geriatric assessment quantifies medical, functional, mental and
      social capabilities and alterations of elders and is the first step to initiate
      specific intervention programs. AIM: To report the initial geriatric assessment
      of a program aimed to help poor elders living in Metropolitan Santiago. SUBJECTS
      AND METHODS: Two thousand one hundred sixteen free living subjects aged 65 to 99
      years old (711 males) were subjected to an assessment using a simple geriatric
      score validated abroad and used previously in Chile. The resulting score ranges
      from 0 (better) to 5 (worst). RESULTS: Eighty eight percent of elders did not
      have problems in the functional evaluation. Subjects over 75 years old needed
      occasional support for the daily activities with higher frequency than younger
      subjects (12 and 5.4% respectively, p < 0.001) and had a higher frequency of
      major functional limitations (7.8 and 3.2% respectively, p < 0.001). Mental
      assessment was considered normal in 89.4% of subjects. Those over 75 years old
      had a higher frequency of memory disturbances (11.4 and 6.5% respectively) and
      cognitive alterations (4.6 and 1.8% respectively). Indefinite social support
      could be received by 84% of subjects, but 7.4% did not have access to this
      resource. CONCLUSIONS: Geriatric assessment of poor elders gives useful
      information to identify those subjects that require community help.

PMID- 9778868
TI  - [Impact of secondary irradiation on operators during coronary arteriography].
AB  - BACKGROUND: The activity over cellular genetic pattern of ionizing radiation can
      produce stochastic and unspecific damages. Interventional cardiology operators
      have increasing exposure times to ionizing radiation and there is no information
      about the real protection conferred by simple radiological protection devices.
      AIM: To assess the magnitude of secondary ionizing radiation exposure of
      operators during conventional coronary arteriography, evaluating the radiation
      exposure during different beam projections and the usefulness of leaded aprons.
      MATERIAL AND METHODS: Ionizing radiation received by operators during coronary
      arteriography was measured using a Geiger-Muller Victoreen model 490 counter. The
      device was placed in the ventral region, covered by the leaded apron and in the
      unprotected dorsal region. Radiation was measured in right and left projections
      during fluoroscopy and shooting. RESULTS: In right projection, the intensity of
      ionizing radiation in ventral and dorsal regions was 1.24 +/- 1.1 and 2.9 +/- 4
      mR/h respectively (p = 0.08). In left projection, the figures were 2.95 +/- 3 and
      7.86 +/- 7.2 mR/h respectively (p = 0.001). During shooting in left projection
      the radiation exposure in ventral and dorsal regions was 9.66 +/- 6.7 and 32.8 +/
      27 mR/h respectively (p < 0.001). During shooting in right projection that
      figures were 10.1 +/- 16 and 20.7 +/- 39.8 mR/h respectively (p = 0.09). No
      correlation between radiation exposure and patients surface area was observed.
      CONCLUSIONS: Secondary radiation received by operators is higher during shooting
      and in left projections. Leaded apron confers a partial protection for ventral
      region, and great fluctuations in the magnitude of radiation exposure were
      recorded. Unprotected dorsal region receives a greater amount of radiation in
      left projections.

PMID- 9778869
TI  - [Comparison of the efficacy of intraarticular and intraarterial injections of two
      betamethasone preparations in patients with osteoarthritis or epicondilytis].
AB  - BACKGROUND: Local infiltration with corticoids is a simple therapy for rheumatic
      disorders devoid of systemic adverse reactions. AIM: To compare the efficacy of
      two betametasone preparations from two different pharmaceutical laboratories in
      the treatment of patients with osteoarthritis or epicondylitis. PATIENTS AND
      METHODS: Fourty patients with knee osteoarthritis and 12 patients with
      epicondylitis were studied. Using a double blind protocol, one of the two
      betametasone preparations was used for local infiltration of the lesions. The
      change in a global score of clinical variables including pain and disability was
      assessed after 30 days of the infiltration. RESULTS: In patients with
      osteoarthritis, the global score decreased significantly with both preparations,
      but no differences were observed between preparations (7.3 +/- 1.8 to 3.9 +/- 2.3
      with preparation A and 7.8 +/- 1.9 to 3.6 +/- 2.3 with preparation B). In
      patients with epicondylitis, pain was also significantly reduced but no
      differences between preparations was observed (7 +/- 2.1 to 1.4 +/- 2.5 for
      preparation A and 4.6 +/- 2.8 to 1.2 +/- 1.6 for preparation B). CONCLUSIONS:
      Local infiltration with both betametasone preparations was equally effective in
      the treatment of patients with knee osteoarthritis or epicondilytis.

PMID- 9778870
TI  - [Efficacy of two gene species in the serological diagnosis of Borrelia
      burgdorferi infections].
AB  - BACKGROUND: There is phenotypic and genetic variability among the species
      Borrelia burgdorferi that produces Lyme disease. Three gene species and seven
      serotypes have been defined. AIM: To study the efficacy of two gene species in
      the serological diagnosis of Borrelia burgdorferi infections in Granada, Spain.
      MATERIAL AND METHODS: One thousand sixty nine sera coming from 1,251 subjects
      without Lyme borreliosis were analyzed. These subjects were studied for health or
      pregnancy controls, differential diagnosis of viral disease, diagnosis of
      syphilis, neurological or rheumatic diseases. In all samples, antibodies against
      Borrelia burgdorferi (B31 and Pko strains) and against Treponema pallidum were
      investigated. Screening tests (ELISA and hemagglutination) were followed by
      confirmations tests for positive samples (Western Blot IgG strain B31 and FTA-abs
      respectively). A clinical and laboratory follow up was done for subjects with
      positive serological tests. RESULTS: The global rate of positive antibodies
      against Borrelia burgdorferi B31 was 8.31% and against the strain Pko was 0.64%.
      Western blot was negative in 36% of subjects with positive ELISA B31. The
      distribution of antibodies against the strain B31 was acute herpes virus
      infection in 16%, gestation in 3%, HIV infection in 6.4%, T pallidum infection in
      36%, rheumatic diseases in 25%, neurological diseases in 17.5% and health
      controls in 7.4%. The percentage of positive Western Blot analyzes were 0.8, 2.1
      and 0.4% respectively. A reversion of positive ELISA tests was observed in 6
      subjects. CONCLUSIONS: The disparity in rates of antibodies against Borrelia
      burgdorferi in different geographic regions may be due to differences in the
      serological tests used. The high rate of false positive ELISA tests underscores
      the need to use other serological tests.

PMID- 9778871
TI  - [Association of the genetic variation of (MSX1-7) and non syndromic cleft lip
      palate in Chilean subjects].
AB  - BACKGROUND: Homeotic genes have regulatory functions during development. It has
      been postulated that the human Msx-1 homeotic gene can be involved in the
      etiology of non syndromic cleft lip palate, since its homologous Msx-1 is
      involved in cleft palate of mice. AIM: To perform an association analysis between
      the genetic variation of Msx-1 and non syndromic cleft lip palate in Chilean
      subjects. PATIENTS AND METHODS: Seventy patients with non syndromic cleft lip
      palate, 136 healthy relatives of these patients and 69 non related normal
      individuals were studied. CA microsatellite in Msx-gene, that was amplified with
      PCR, was studied. RESULTS: No differences in the genetic frequencies of Msx-1
      alleles, were observed in the three groups studied. Allelic heterogeneity for
      allele 2 seems to be related to cases of non syndromic cleft lip palate from
      multiplex families and heterogeneity for allele 3 is related with simplex
      families cases. CONCLUSIONS: These results seem to support the hypothesis of
      genetic heterogeneity in the etiology of non syndromic cleft lip palate.

PMID- 9778873
TI  - [Inferior vena cava filters. Indications and results in 111 patients].
AB  - BACKGROUND: Anticoagulation is the treatment of choice for deep vein thrombosis
      and pulmonary embolism. Occasionally this treatment is contraindicated or fails
      to prevent pulmonary embolism. In these patients, inferior cava vein interruption
      is indicated and filter insertion is the procedure commonly performed. AIM: To
      report the results of inferior cava vein filter insertions in 111 patients.
      PATIENTS AND METHODS: A retrospective review of patients in whom inferior cava
      vein filters were inserted was performed. RESULTS: During the period 1983-1997,
      filters were inserted in 111 patients (56 female) aged 15 to 93 years old.
      Indications were pulmonary embolism with contraindication or failure of
      anticoagulation therapy or poor respiratory function (58 patients), deep vein
      thrombosis and contraindication for anticoagulation (32 patients) and other
      indications in 20 patients. In 47 patients, treated before 1993, the insertion
      required a cut-down. Since then, a percutaneous approach was used in the
      remaining 64 cases. Three insertion attempts failed, all using cut-down. One of
      these patients died due to a massive pulmonary embolism. In 88% of the patients
      the jugular vein was the access site and in 10 patients, the filter was
      deliberately deployed above the renal veins. There was no mortality or
      complications. Patients were followed during a maximal period of 147 months and
      27 died of unrelated disorders. Survival at 5 and 10 years was 63 and 47%
      respectively. Symptomatic inferior cava vein obstruction was detected in 5
      patients during the follow up period. CONCLUSIONS: Inferior cava vein filter
      insertion is a safe measure to prevent pulmonary embolism and its consequences.

PMID- 9778872
TI  - [Cardiac rhythm and systemic embolism in long-term follow up of patients with non
      valvular paroxysmal atrial fibrillation].
AB  - BACKGROUND: Paroxysmal atrial fibrillation may predispose to systemic embolism.
      There is little information about the evolution of cardiac rhythm and the
      occurrence of new embolic events in these patients. AIM: To report the results of
      a long term follow up of patients with paroxysmal atrial fibrillation. PATIENTS
      AND METHODS: Patients consulting for non valvular paroxysmal atrial fibrillation
      were followed for a mean period of 5 years. An EKG, 2D echocardiogram and brain
      CT scans were performed on admission and at the end of the follow up period to
      all patients. RESULTS: Sixty eight patients aged 65 +/- 1.5 years were studied.
      Thirty two had an idiopathic atrial fibrillation, 28 had a history of mild
      hypertension and 8 had a history of coronary artery disease. Evidence of systemic
      emboli was found in 17 patients at entry (to the brain in 14 patients). During
      the follow up 87% of patients required antiarrhythmics, 27% were anticoagulated
      and 28% received aspirin. Five patients had new embolic episodes. Of these, four
      had a history of prior embolism. Forty one percent of patients continued in sinus
      rhythm and remained asymptomatic, 32% had at least one recurrence of paroxysmal
      atrial fibrillation and nine patients evolved to chronic atrial fibrillation.
      Five patients required a permanent pacemaker due to symptomatic bradycardia.
      CONCLUSIONS: Most patients with non valvular paroxysmal atrial fibrillation
      remain in sinus rhythm but one third have recurrences of the arrhythmia. A main
      risk factor for embolism is the history of previous embolic episodes.

PMID- 9778874
TI  - [Partial left ventriculectomy for end stage dilated cardiomyopathy. Is it an
      alternative for heart transplantation?].
AB  - We present a case of a 60 year old male with end stage dilated cardiomyopathy in
      NYHA functional class IV in whom a partial left ventriculectomy was performed, a
      new surgical procedure developed in Brazil and done for the first time in Chile.
      Left ventricular size reduction produced an objective improvement on
      echocardiographic parameters of left ventricular function as well as in patient's
      NYHA functional class in the early post operative period.

PMID- 9778875
TI  - [Diffuse sclerosing papillary thyroid carcinoma. Report of two cases].
AB  - Unlike classical papillary carcinoma, diffuse sclerosing papillary thyroid
      carcinoma presents as a diffuse goiter with a discretely irregular surface,
      associated to hypo or hyperthyroidism, specially in young women. We report two
      women aged 41 and 23 years old with this disease, one with normal thyroid
      function and the other with hyperthyroidism. It is concluded that diffuse
      sclerosing papillary thyroid carcinoma must be suspected in patients with rapidly
      growing goiter with irregular surface or diffuse minute calcifications, specially
      in the presence of hypo or hyperthyroidism. Fine needle aspiration is a good
      diagnostic procedure.

PMID- 9778876
TI  - [Myxoma and antiphospholipid antibody syndrome].
AB  - We report a 26 years old female with a Cerebral Palsy as a consequence of a
      perinatal vascular accident. She was admitted in August 1996 with a left
      hemiplegia due to a right M1 median artery thrombotic occlusion, as demonstrated
      by magnetic resonance imaging angiography. Transesophagical bi-dimensional
      echocardiography showed a right atrial myxoma and ruled out the persistence of an
      oval foramen. The study of coagulation disorders lead to the diagnosis of a
      primary antiphospholipid syndrome. We postulate that interleukin-6 produced by
      the myxoma could trigger an immunological reaction leading to the primary
      antiphospholipid syndrome.

PMID- 9778877
TI  - [Biomedical papers written by Chilean authors published in international journals
      in 1997. A review of MEDLINE].
AB  - BACKGROUND: Many Chilean biomedical investigators publish the results of their
      research in international journals, not easily accessible to fellow physicians of
      the country. AIM: To assess the amount and quality of papers published by Chilean
      authors in international journals. DATA SOURCE AND METHODS: Using MEDLINE
      databases from January to August, 1997, all papers in which Chile appeared in the
      field "AD" (Address of author) were selected. Papers with a clear relationship to
      human medicine were identified. RESULTS: During the study period, 390 papers with
      authors residing in Chile appeared in MEDLINE. Of these, 188 (48%) were published
      in Chile and the rest was published abroad. Thirty manuscripts had a greater
      relationship to clinical medicine and the authors of nine of them were invited to
      submit a translation of their abstract into Spanish to have them reproduced in
      the present article. CONCLUSIONS: A significant proportion of biomedical research
      papers originated in Chile is published abroad with the consequent lack of
      diffusion among non-specialized readers from their own country.

PMID- 9778878
TI  - [Anticoagulation in atrial fibrillation: not yet settled].
AB  - A great deal of interest has received atrial fibrillation, the most common
      arrhythmia in adults, due to its complications and difficult treatment its most
      dreaded complication is atrial thrombi formation with the subsequent risk of
      embolization. There are several reports defining risk factors for embolic
      complications and the usefulness of anticoagulants for their prevention. We
      review the state of the art of anticoagulation in atrial fibrillation not
      associated to rheumatic valvulopathy. We also give tools to assess embolic risk
      and to determine the anticoagulant choice for the different presentation forms of
      atrial fibrillation.

PMID- 9778879
TI  - [Laboratory diagnosis of Lyme borreliosis].
AB  - Some direct methods that can be used for the diagnosis of Lyme borreliosis are
      the culture, direct visualization or the detection of microbial DNA using
      polymerase chain reactions, in body tissues or fluids. Unfortunately, all these
      methods have a low sensitivity. There is a wide assortment of tests and antigens
      for indirect diagnosis, and the most recommended are ELISA tests and Western
      blot. The main inconvenient of these tests are the existence of shared serologic
      reactions, the variability of immune response and the difficult interpretation of
      results. Therefore, we propose the following guidelines for the diagnosis of Lyme
      borreliosis: For sero-epidemiological studies and to diagnose infection,
      antibodies should be determined in subjects with a compatible clinical picture,
      using an ELISA test that must be positive in at least two separate samples. All
      positive ELISA results should be confirmed with Western blot analysis, that must
      be interpreted using established criteria. Polymerase chain reactions should be
      used when they are available.

PMID- 9778880
TI  - [Accreditation professional degrees and teaching institutions: the case of
      Chile].
AB  - Accreditation has acquired special relevance for the habilitation of professional
      practice, considering the proliferation of teaching institutions, the variety of
      training programs and the increasing amount of professionals requiring
      accreditation or revalidation of their titles. The internationalization of
      professional activities requires global and uniform accreditation procedures to
      avoid inequalities in evaluation of different professionals coming from abroad or
      from Chile. In the scope of medical practice, these concepts acquire special
      relevance, considering the appearance of new medical schools in the last decade
      and the increasing number of foreign physicians that need to revalidate their
      titles. In the period between January 1996 and September 1997, 192 foreign
      physicians applied to revalidate their titles and only 55 were approved.
      Therefore, the establishment of and effective evaluation system will correct
      deficiencies in the accreditation process and will promote the revision of
      training programs and the progress of teaching institutions. The organisms that
      will require to be accredited must be confident that this action will improve the
      quality of Chilean professional training.

PMID- 9778881
TI  - [Polyarthritis in hepatitis C virus infection].

PMID- 9778882
TI  - Science, medical practice and ethics in the next millennium.

PMID- 9778884
TI  - Risk factors for protein-energy malnutrition in pre-school shantytown children in
      Sao Paulo, Brazil.
AB  - OBJECTIVES: To investigate the health and nutritional conditions of people living
      in a shantytown in the city of Sao Paulo in order to identify risk factors for
      infant malnutrition. DESIGN: A retrospective cohort study. PARTICIPANTS: Children
      living in a shantytown was conducted among children less than 72 months of age.
      METHODS: Home visits were made and information was collected regarding the risk
      factors for malnutrition. RESULTS: The prevalence of chronic malnutrition was
      41.6% according to Gomez, 36.6% according to Waterlow, and 17.6% according to
      WHO. Risk factors for malnutrition, according to the weight-for-age index,
      included birthweight, presence of upper respiratory tract infections, number of
      pregnancies, number of births, maternal body mass index, birthplace of father,
      and home building material; according to the weight-for-height index, they
      included birthweight and maternal age at the time of birth; and according to the
      height-for-age index, they included the number of prenatal medical visits,
      birthweight, maternal height, maternal body mass index, father's employment being
      unregistered, and maternal birthplace. An instrument for identifying children at
      risk of malnutrition was devised from these major risk factors for future
      malnutrition, which may then be applied to newly-born children.

PMID- 9778883
TI  - Management of primary headache in emergency services of Santos and surrounding
      towns.
AB  - OBJECTIVES: Primary headaches are often seen by Clinicians on duty at Emergency
      Services. We have investigated the treatment of such patients by 43 medical
      doctors who have been working at Emergency Services in the city of Santos and
      surrounding towns for many years. RESULTS: We confirmed the high prevalence of
      primary headaches in Emergency Services. There seem to be diagnosis difficulties
      concerning differentiating attacks of migraine and tension type headache. We also
      observed that IV dipirone was the most frequently prescribed treatment for
      patients with primary headaches in this study. There is no protocol in the
      literature which recommends IV dipirone for the treatment of migraine attacks or
      other primary headaches. CONCLUSION: It would be advisable to perform controlled
      double blind studies in order to verify the advantages of IV dipirone in the
      treatment of intense attacks primary headaches. We concluded that headache
      management recycling programs could be of interest for doctors who regularly work
      at Emergency Services.

PMID- 9778885
TI  - Nurses' attitudes towards alcoholism: factor analysis of three commonly used
      scales.
AB  - OBJECTIVE: To investigate the psychometric properties of three scales commonly
      used to measure attitudes and beliefs about alcoholism. DESIGN: Cross-sectional
      study using a systematic sample. SETTING: Hospital Sao Paulo (a public general
      tertiary hospital) and the adjoining Federal University of Sao Paulo, Brazil.
      PARTICIPANTS: 310 nurses and nursing teachers. INSTRUMENTS: The Marcus Alcoholism
      Questionnaire, The Seaman Mannello Nurses' Attitudes Towards Alcohol and
      Alcoholism Scale and The Tolor-Tamarin Attitudes Towards Alcoholism Scale, which
      were combined into one self-administered questionnaire. ANALYSIS: The scales were
      re-grouped into their original formats and each underwent a principal components
      analysis with orthogonal rotation of factors. RESULTS: Each scale was found to
      consist of three main factors. There was some degree of overlap in the nature of
      the factors that the scales measured but each scale also measured something
      unique. CONCLUSION: The results of this comparative analysis could be used as a
      basis for developing a new scale covering all the important attitudinal groups
      identified by this study.

PMID- 9778886
TI  - How should PCNA be assessed? Total of stained cells or only the most intensely
      stained ones?
AB  - OBJECTIVE: This study aimed to analyse whether a marker of proliferative activity
      (PCNA) could provide a prognosis of tumor evolution and to determine whether
      different interpretation criteria could alter the results. METHOD: The presence
      of PCNA in 59 patients of state II (T2 N0.1 M0) mammary carcinoma was determined.
      RESULT: Numerical proportions of total and intensely stained cells were
      established. These data were compared with anatomopathological parameters. A
      significant association between higher cyclin values and worse histological and
      nuclear grading was encountered, particularly in patients with a "negative
      axilla" using the PCNA index. Cyclin values were not significant in relation to
      any parameters when indices from the intensely stained cells were considered
      exclusively. CONCLUSION: Higher nuclear (NG3) and histological (HGIII) grading,
      associated with a high PCNA index (> 50), distinguish high-risk patients, and it
      is more appropriate considering all the stained cells as representative of PCNA
      indices, thus reflecting tumor aggressiveness.

PMID- 9778887
TI  - Effects of massive transfusion on oxygen availability.
AB  - OBJECTIVES: To determine oxygen derived parameters, hemodynamic and biochemical
      laboratory data (2,3 Diphosphoglycerate, lactate and blood gases analysis) in
      patients after cardiac surgery who received massive blood replacement. DESIGN:
      Prospective study. SETTING: Heart Institute (Instituto do Caracao), Hospital das
      Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Brazil. PARTICIPANTS:
      Twelve patients after cardiac surgery who received massive transfusion
      replacement; six of them evolved to a fatal outcome within the three-day
      postoperative follow-up. MEASUREMENTS AND MAIN RESULTS: The non-survivors group
      (n = 6) presented high lactate levels and low P50 levels, when compared to the
      survivors group (p < 0.05). Both groups presented an increase in oxygen
      consumption and O2 extraction, and there were no significant differences between
      them regarding these parameters. The 2,3 DPG levels were slightly reduced in both
      groups. CONCLUSIONS: This study shows that patients who are massively transfused
      following cardiovascular surgery present cell oxygenation disturbances probably
      as a result of O2 transport inadequacy.

PMID- 9778888
TI  - Hairy cell leukemia: a histo-cytochemical and ultra-structural study.
AB  - We studied five patients with hairy cell leukemia (HCL) diagnosed within the last
      ten years at the Department of Hematology of Universidade Federal de Sao Paulo
      Escola Paulista de Medicina. Our purpose was to analyze the value of transmission
      electron microscopy (TEM) by comparing this method with the conventional ones. At
      diagnosis, patients presented weight loss, spleen enlargement and hairy cells
      (HC) in peripheral blood and bone marrow slides. HC was characterized by
      morphology and tartrate test resistance in the acid phosphatase reaction (TRAP).
      At the evaluation time, the amount of HC ranged from 1% to 85% of WBC count. All
      patients, except two, had phenotype B. In these last two, TRAP as well as
      phenotype B could not be documented due to low HC numbers in their exams.
      Cytoplasmatic projections and the absence of lamellar ribosomic complex were the
      most frequent ultrastructural findings, even in those patients with the lowest HC
      numbers. Based on these features, TEM is an efficient method for searching for HC
      at HCL diagnosis and during the course of the disease.

PMID- 9778889
TI  - From thesis to publication of a paper: some ideas and suggestions.

PMID- 9778890
TI  - Granulocytic sarcoma presented as a reactivation of chronic myeloid leukemia
      after allogenic marrow transplantation.
AB  - The authors report the case of a chronic myeloid leukemia (CML) patient submitted
      to allogenic bone marrow transplantation, who had probably never entered complete
      remission. The disease was reactivated as a granulocytic sarcoma, next to a
      platinum plate installed to correct a tibia fracture 11 years earlier. Its final
      event was a myeloid Ph1 + blastic crisis that was unsuccessfully treated with
      high doses of sc interferon and citarabine.

PMID- 9778891
TI  - [The future of physiology (the introductory address to the opening of the 33rd
      International Congress on the Physiological Sciences. Saint Petersburg, 30 June
      1997)].

PMID- 9778892
TI  - [The interaction of physiological and psychological mechanisms in the adaptation
      process].

PMID- 9778893
TI  - Chronomes render predictable the otherwise-neglected human "physiological range":
      position paper of the BIOCOS project. BIOsphere and the COSmos.
AB  - On June 30, 1997, the Russian Academy of Medical Sciences convened a special
      session at its headquarters to discuss and, at the end of this meeting, to
      unanimously endorse a project on "The BIOsphere and the COSmos" (BIOCOS), a
      follow-up on various international resolutions reviewed elsewhere [1]. BIOCOS
      recommends the introduction of the science of the body's time structure,
      chronobiology [2], into basic science and health and environmental care via
      national physiological and physical monitoring and educational endeavors. More
      specifically, BIOCOS aims at the collection and archivization for basic and
      applied purposes at different latitudes and longitudes of physical and
      physiological time structures, or chronomes [1, 3]. The first step of BIOCOS is
      the systematic mapping of variation in human blood pressure and heart rate from
      womb to tomb and the opportunistic mapping of other variables in human and other
      life forms. On July 1, 1997, BIOCOS was introduced at the XXXIII International
      Congress of the International Union for Physiological Sciences in St. Petersburg,
      in the context of a symposium on "Adaptation to the Environment". Thereafter,
      BIOCOS was presented in a course on chronobiology in Mexico City, August 27-30,
      1997, in lectures at Masaryk University, Brno, Czech Republic (September 1,
      1997); at a meeting on "Chronobiology with roots in the cosmos", September 2-6,
      1997, in Stara Lesna, Slovakia, under the auspices of the Slovak Medical Society;
      at Safarik University in Kosice (September 8) and the Institute of Clinical
      Endocrinology in Lubochna (September 9), both in Slovakia and at the
      International Conference on the Pineal Gland and Cancer (October 2-5, 1997) in
      Blaubeuren, Germany.

PMID- 9778894
TI  - Conflicts of thermal adaptation and fever--a cybernetic approach based on
      physiological experiments.
AB  - Cold adaptation aims primarily at a better economy, i.e., preservation of energy
      often at the cost of a lower mean body temperature during cold stress, whereas
      heat adaptation whether achieved by exposure to a hot environment or by
      endogenous heat produced by muscle exercise, often brings about a higher
      efficiency of control, i.e., a lower mean body temperature during heat stress, at
      the cost of a higher water loss. While cold adaptation is beneficial in a cold
      environment, it may constitute a detrimental factor for exposure to a hot
      environment, mainly because of morphological adaptation. Heat adaptation may be
      maladaptive for cold exposure, mainly because of functional adaptation. Heat
      adaptation clearly is best suited to avoid higher body temperatures in fever, no
      matter which environmental conditions prevail. On the other hand, cold adaptation
      is detrimental for coping with fever in hot environment. Yet, in the cold,
      preceding cold adaptation may, because of reduced metabolic heat production,
      result in lower febrile increase of body temperature. Apparently controversial
      effects and results may be analyzed in the framework of a cybernetic approach to
      the main mechanisms of thermal adaptation and fever. Morphological adaptations
      alter the properties of the heat transfer characteristics of the body ("passive
      system"), whereas functional adaptation and fever concern the subsystems of
      control, namely sensors, integrative centers and effectors. In a closed control
      loop the two types of adaptation have totally different consequences. It is shown
      that the experimental results are consistent with the predictions of such an
      approach.

PMID- 9778895
TI  - [The systems-forming role of antihypoxic mechanisms in body adaptation to extreme
      environmental conditions].

PMID- 9778896
TI  - [The physical work capacity of divers during prolonged deep-water immersions].

PMID- 9778897
TI  - [An experiment to study the information-dependent ecological consciousness of
      upper-grade secondary school students (the attitude of upper-grade secondary
      school students to ecological problems in relation to their personality traits)].

PMID- 9778898
TI  - [Brain processing of visually presented verbal stimuli at different levels of
      their integration. II. The orthographic and syntactic aspects].

PMID- 9778899
TI  - [Changes in the event-related potentials during the classification of images].

PMID- 9778900
TI  - [Reverse adaptation studied by recording short-latency auditory evoked
      potentials].

PMID- 9778901
TI  - [The probability patterns of narrow-band difference spectra in the human EEG in
      dynamic memory activity].

PMID- 9778902
TI  - [The dependence of the intensity of emotional feeling on the intensity of the
      need and of its probability of satisfaction: subjective and objective estimates].

PMID- 9778903
TI  - [The spatial-temporal structure of graphic movements].

PMID- 9778904
TI  - [How does body posture affect the blood flow in parenchymatous organs? I. The
      liver].

PMID- 9778905
TI  - [The effect of different tolerance-developing physical exercises on the blood
      biochemical indices in highly qualified female athletes].

PMID- 9778906
TI  - [The blood rheological profiles of patients with arterial hypertension and a
      hyperviscosity syndrome].

PMID- 9778908
TI  - [The electrophoretic mobility of the erythrocytes in gamma-globulin-enriched
      blood].

PMID- 9778907
TI  - [The role of sports training in the efficiency of oxygen regimens in children in
      the North].

PMID- 9778909
TI  - [The indices of urinary tribulin activity as an indicator of psychological traits
      and of hemodynamic status].

PMID- 9778910
TI  - [The phasic structure of the cardiac cycle in the normal left and right heart
      ventricles].

PMID- 9778912
TI  - [Emotional tension during an occupational psychological examination].

PMID- 9778911
TI  - [Immune homeostasis in the permanent inhabitants of mountain regions].

PMID- 9778913
TI  - [The indices of cholesterol esterification in different groups of inhabitants in
      northern European Russia].

PMID- 9778914
TI  - Histological grading of malignancy correlates with regional lymph node metastasis
      and survival of patients with oral squamous cell carcinoma.
AB  - This study evaluated the effectiveness of certain clinical and pathologic
      parameters in prognosing in oral squamous cell carcinoma (O-SCC). Patients and
      Methods. We performed a univariate and multivariate analysis of 212 patients with
      O-SCC and thus determined the move valuable factors in making a prognosis. We
      then investigated the relationships among the various pathologic parameters and
      regional lymph node metastasis. Regarding the pathologic parameters, a
      multivariate analysis using Cox's proportional hazard model determined
      inflammatory infiltration, invasive tendency, necrotic tendency, mitotic figures,
      and vascular permeation to be significant and independent prognostic factors
      affecting O-SCC. In addition, such the pathologic parameters as the mode of
      invasion, cellular atypia, mitotic figures, a necrotic tendency and as invasive
      tendency all correlated with the occurrence of regional lymph node metastasis.
      These statistically estimated histological grading of malignancy was thus found
      to be clinically acceptable and useful in helping to make a prognosis of O-SCC
      patients.

PMID- 9778915
TI  - Prevalence of hepatitis C virus antibody in patients on chronic hemodialysis.
AB  - Hepatitis C virus antibody (anti-HCV) was studied in 267 patients undergoing
      maintenance hemodialysis using an anti-HCV enzyme-linked immunosorbent assay.
      Furthermore, both hepatitis B virus core antibody (anti-HBc) and human T cell
      leukemia virus type 1 antibody (anti-HTLV-1) were determined in these patients to
      compare their prevalence rates. Seventy one patients (27%) had positive anti-HCV,
      134 patients (50%) positive anti-HBc and 40 patients (15%) positive anti-HTVL-1.
      Among the 183 patients who had received blood transfusion, the prevalence of
      these antibodies was 34% for anti-HCV, 56% for anti-HBc and 17% for anti-HTLV-1,
      respectively. A significance between those with and without blood transfusion was
      recognized for anti-HCV (p < 0.001) and anti-HBc (p < 0.01). Of 56 patients who
      had received hemodialysis for over 15 years, the positive antibody was found in
      63% for anti-HCV (p < 0.001), 73% for anti-HBc (p < 0.001) and 25% for anti-HTLV
      1 (p < 0.05), which was significantly higher than that of patients receiving a
      less than 15 years hemodialysis. The prevalence rates of anti-HCV and anti-HTLV-1
      did not increase with age, while that of anti-HBc increased. These findings
      suggest that blood transfusions during hemodialysis play a very important role in
      the infection of hepatitis C virus.

PMID- 9778917
TI  - [A case of lymphocytic interstitial pneumonia].
AB  - A 56-year-old female was admitted on November 1995 to our hospital because of the
      abnormal shadow on her chest X-ray. Although the chest X ray film revealed
      diffuse reticulonodular shadows in the bilateral lung fields and right hilar
      lymphadenopathy, she had not any complaints. Furthermore, mediastinal
      lymphadenopathy and polyclonal hypergammaglobulinemia were noted. For a further
      examination, transcutaneous thoracoscopic lung biopsy was performed on August
      1996. The lung specimens showed a interstitial infiltration of small lymphocytes
      exclusively around bronchioles. And the diagnosis of lymphocytic interstitial
      pneumonia (LIP) was made. She had been suffered from bronchial asthma for 27
      years. This is the first report of LIP accompanied with bronchial asthma. Its
      relationship between LIP and bronchial asthma remains unclear. In the 2 years of
      follow-up, she remained asymptomatic with unchanged chest radiogram. And her
      pulmonary function was preserved for the 2 years. But lymphocytic interstitial
      pneumonia may induce malignant lymphoproliferative disease potentially, we should
      carefully follow up.

PMID- 9778916
TI  - Relationship of hepatitis C virus genotypes and viremia levels with development
      of hepatocellular carcinoma among Japanese.
AB  - The roles of hepatitis C virus (HCV) genotypes and viremia levels in the
      pathogenesis of hepatocellular carcinoma (HCC) were examined in case-control
      analyses of 69 patients with HCC, 55 patients with liver cirrhosis (LC) without
      HCC, and 30 controls undergoing health examinations. Major HCV genotypes
      (genotypes 1 and 2) were determined by both reverse transcription-polymerase
      chain reaction (RT-PCR)-based and serological assays, and the HCV-RNA level by a
      branched DNA assay. Genotype 1 was detected in 68-82% of HCCs, 71-73% of LCs, and
      50-72% of controls. Based on RT-RCR, the relative risk for genotype 1 vs. 2
      contrasting either HCC or LC patients with controls was estimated at 3.6 (95%
      confidence interval: 1.1-12.5) for HCC and 4.8 (1.1-20.4) for LC, whereas no risk
      excess was evident for the occurrence of HCC in LC (relative risk: 0.7). The
      corresponding association based on the serological assay was somewhat weaker and
      statistically insignificant. No significant difference in age or time lapse after
      blood transfusion was observed according to the genotype. The HCV-RNA titer for
      genotype 1 was significantly lower among HCC patients than among LC patients or
      controls. Genotype 1 HCV may be associated with HCC through affecting relatively
      early stages of liver diseases progression prior to the establishment of LC.

PMID- 9778918
TI  - Staining for histologic diagnosis of aluminum osteopathy--application of confocal
      laser scanning microscopy to observation for offminum in bones from aluminum
      treated, subtotally nephrectomized rats.
AB  - To histologically detect excess aluminum (Al) taken up by bones in a rat model of
      renal failure prepared by 5/6-nephrectomy, non-decalcified bone tissue sections
      from specimens of the tibia, femur, rib and ilium were stained with a newly
      developed lumogallion reagent and examined for aluminum by confocal laser
      scanning microscopy. The assay revealed that Al contents in the tibia and femur
      of Al-treated rats tended to be a few-fold higher, compared to controls. With the
      lumogallion stain technique, Al in bones could be detected and identified at Al
      concentrations of > or = 9.0 micrograms/g in bone tissues. The reaction of the
      metal with lumogallion is specific and proved to be positive even at
      concentrations of excess Al so low as to be undetectable by conventional methods.
      The present observation disclosed that, unlike the generally accepted view, the
      Al was accumulated not in the calcification front but was distributed diffusely
      or as aggregates at high concentration in osteoid tissues. Z mode scans of the
      slides permitted steric delineation of the state of Al accumulation in bone
      tissues. The method described herein is considered a useful means for clinical
      diagnosis of aluminum osteopathy.

PMID- 9778919
TI  - The human gemelli muscles and their nerve supplies.
AB  - The superior and inferior gemellus muscles were examined as to their forms and
      the patterns of nerve supply in 13 human cadavers (20 specimens). The superior
      gemellus muscle (Gs) was absent in 3 specimens, but showed no accessory slip or
      fusion with the internal obturator muscle (Oi). The nerve to the Gs originated
      from the nerve to the Oi (OiN) in 7, the nerve to the quadratus femoris muscle
      (QfN) in 4, or both in 6 specimens. The inferior gemellus muscle (Gi) was present
      in all, but fused with the Oi in 3 specimens. In one specimen, an accessory
      muscle bundle was observed between the Gi and Oi. The Gi always received branches
      from the QfN at its anterior surface, but received an additional nerve supply at
      its posterior surface from the OiN or the pudendal nerve in one specimen each,
      and the accessory bundle was supplied by a branch from the OiN at its posterior
      surface. In a well preserved specimen, a branch to the Gi from the QfN entered
      the Oi and communicated with the OiN after supplying and leaving the Gi. The
      frequency of the dual innervation of Gs by the OiN and QfN was 29.3%, but that of
      the Gi and Oi could not be determined, because of the occurrence of the fused
      part, the accessory bundle and nerve communication. There existed some gross
      anatomical differences between both gemelli muscles; they are considered to be
      parts of the internal obturator muscle in a broad sense.

PMID- 9778920
TI  - [Immunocytochemical studies on the endothelin peptides and their receptors in
      mast cells of the rat lung and gastrointestinal tract].
AB  - The distribution of endothelin (ET)-containing mast cells was
      immunohistochemically investigated in the rat lung and gastrointestinal tract
      using antibodies against Big ET-1, Big ET-2, Big ET-3, mature ETs and their
      receptors of ET-A, and ET-B. In the lung, numerous mature ETs-containing mast
      cells were present in connective tissue around the bronchus, bronchioles and in
      the interalveolar septa. The number of Big ET-2-containing mast cells was almost
      the same as that of Big ET-3-containing mast cells, while Big ET-1-positive mast
      cells were fewer than that of the other isopeptides. In all the regions of the
      gastrointestinal tract, immunoreactivity for mature ETs was found mainly in mast
      cells of the lamina propria, the number of Big ET-2 and Big ET-3-containing cells
      was almost the same similar to that found in the lung, while Big ET-1-containing
      cells were very few. Moreover, mast cells in not only lung but also
      gastrointestinal tract contain both of ET-A and ET-B receptors. Electron
      microscopically, ET-immunoreaction products were mainly precipitated in the mast
      cell granules. Hence, we presume that ETs are synthesized in and secreted from
      mast cells in the rat lung and gastrointestinal tract; they act in an
      autocrine/paracrine fashion; and their main isopeptides are ET-2 and ET-3.

PMID- 9778921
TI  - [The health of population in Siberia and current problems of occupational
      medicine].

PMID- 9778922
TI  - [Results and prospects of scientific research at the Scientific Research
      Institute of occupational medicine and human ecology].

PMID- 9778923
TI  - [Today and tomorrow of the Ekaterinburg Medical Scientific Center of Preventive
      Medicine and Health Protection of Workers of industrial enterprises].

PMID- 9778924
TI  - [Problems of occupational medicine in the activity of the Novosibirsk medical
      scientific-research institute].

PMID- 9778925
TI  - [Occupational medicine as an integral part in the scientific-research pedagogical
      and clinical activities of a medical institution of higher learning (on the
      example of 75-year-long work of the department of occupational medicine of the
      St. Petersburg Graduate Medical Academy].

PMID- 9778926
TI  - [Sixty-seven years together with the Scientific-Research Institute of
      Occupational Medicine].

PMID- 9778927
TI  - [On the mechanism underlying general toxicity of chemicals].

PMID- 9778928
TI  - [Medical-biological and economic criteria and mechanisms in the health
      preservation among workers].

PMID- 9778929
TI  - [Arterial hypertension in transportation workers: epidemiology, aspects of health
      management, transportation safety, unresolved problems].

PMID- 9778930
TI  - [The role of occupational medicine in the development of current and future legal
      documents on women's work safety and women's health].
AB  - The article covers legal documents of general and specific measures for women's
      work safety and health care. Legal basis for work safety and health care in women
      of childbearing age in this country corresponds with international legal norms.
      Preservation of social and biologic prosperity for women in this country should
      be guaranteed by "On protection of maternity" law including medical, social,
      economic and legal measures.

PMID- 9778931
TI  - [Results and goals of scientific research on "Work and health of medical
      personnel"].

PMID- 9778932
TI  - [Improvement of detectability of microcalcifications by magnification digital
      mammography].
AB  - Our aim in this study was to evaluate the potential utility of magnification
      mammography with a CR system by investigating the basic imaging parameters and
      detectability of microcalcifications in comparison with those of conventional
      screen-film systems. The basic imaging parameters were evaluated by measuring
      scatter fraction, modulation transfer function (MTF), Wiener spectrum, and
      incident dose for the various magnification factors. The detection of simulated
      microcalcifications in radiographs of a mammographic phantom and breast specimens
      were evaluated subjectively and quantitatively for screen-film and CR techniques
      with various magnification factors. The scatter fraction of digital magnification
      mammography decreased with increasing magnification factor. MTF of magnification
      digital mammography improved with increasing magnification factor. The
      detectability of microcalcifications with the CR system was significantly
      improved by magnification technique. From the above results, it is expected that
      the use of magnification mammography with a CR system will improve the
      detectability of microcalcification.

PMID- 9778933
TI  - [High signal intensity of globus pallidus on T1-weighted MRI in liver cirrhosis
      patients: clinical and pathological study].
AB  - In some patients with liver cirrhosis, the globus pallidus shows high signal
      intensity on T1-weighted MRI. The relationship was examined between high signal
      intensity on T1-weighted images and pathological conditions such as liver
      function, portal venous pressure and metal concentrations in brain. The signal of
      the globus pallidus on T1-weighted imaging became highly enhanced in accordance
      with prolongation of prothrombin time, deterioration of ICG R15, or decrease in
      choline esterase and the Fisher ratio. Furthermore, the high signal intensity was
      also seen in patients with high portal pressure and large varices. In
      histopathological study, remarkable atrophy and loss of nerve cells were observed
      in globus pallidus with high signal intensity on T1-weighted imaging, changes
      that were similar to those in with patients with manganese poisoning. The
      manganese concentration in autopsied globus pallidus with high signal intensity
      on T1-weighted imaging showed a 9.5-fold increase compared with that with normal
      intensity. In conclusion, the deposition of manganese in the globus pallidus,
      which is accompanied with the nerve cell deciduation, brings about the high
      signal intensity of the globus pallidus on T1-weighted MRI in patients with liver
      cirrhosis.

PMID- 9778934
TI  - [MRI phase contrast flow measurement of portal vein: influence and compensation
      of respiratory motion and propriety of phase correction using background].
AB  - The purposes of this study were to (1) determine which condition, breath holding
      (BH) or quiet breathing (QB), is better for phase contrast (PC) measurement of
      the portal flow (PF); (2) assess the usefulness of respiratory compensation (RC),
      a technique that diminishes motion artifacts due to breathing, on PC flow
      measurement; and (3) evaluate the propriety of phase correction (PhC) using
      background for PC flow measurement. For purposes (1) and (2) respiratory
      simulation phantom (RSP) was measured, and PF measurements were performed in 6
      healthy subjects (HS) and 53 patients. Thirty of the patients had liver cirrhosis
      (LC) and 23 did not. For purpose (3), flow measurements were carried out in the
      phantom and 6 HS. (1) In 6 HS, intra-subjective coefficients of variation (CV)
      were smaller under QB than under BH (p < 0.05). And PF in patients with LC was
      less than in those not under QB (p < 0.01). This difference was not statistically
      significant under BH. (2) In the RSP study PC flow measurement with high sort RC
      showed good reliability. (3) Intraobserver variation was smaller without PhC than
      with PhC (p < 0.05) in the HS study. It may be more useful to perform portal flow
      measurements under QB with RC and without PhC than with PhC or under BH.

PMID- 9778935
TI  - [Clinical efficacy of concurrent carboplatin, etoposide, and definitive
      radiotherapy for stage III non-small-cell lung cancer: consideration as to
      therapeutic outcomes and morbidity].
AB  - To improve the therapeutic outcome for inoperable non-small-cell lung cancer, we
      applied definitive thoracic radiotherapy combined with concurrent administration
      of carboplatin and etoposide. We retrospectively analyzed 55 eligible patients
      with Stage III disease. The one-year rate of overall survival (OAS) and distant
      metastasis-free survival (DMFS) of the total group were 46.1% and 36.1%,
      respectively. Twenty-nine patients developed thoracic failures (52.7%) and 23
      (41.8%) distant failures. Using univariate and multivariate analyses, radiation
      dose, performance status and LDH were revealed as significant prognostic factors
      of OAS, and LDH had a strong adverse effect on DMFS. Leucopenia of Grade 3 or
      higher was noted in 75.9%, anemia in 55.6%, thrombocytopenia in 59.3%,
      esophagitis in 20.4%, and lung injury in 10.9%. Sufficient gain was not obtained
      by our strategy, and higher morbidity, especially of lung, was noted than was
      expected. It was suspected that simultaneous use of oral etoposide might increase
      radiation pneumonitis, so one should take special care of unexpected toxicity in
      concurrent chemoradiotherapy. Both the hyperfractionated technique of
      radiotherapy and the time-dose modification of anti-tumor drugs should be
      considered in further steps.

PMID- 9778936
TI  - [Results of preoperative high-dose-rate intraluminal brachytherapy for resectable
      rectal cancer].
AB  - One hundred and fifteen patients with middle and lower rectal cancer were treated
      with preoperative High-dose-rate intraluminal brachytherapy (HDRIBT) and radical
      operation. Patients were divided into a middle-dose group (group A; 30-40 Gy; n =
      94) and a high-dose group (group B; 60-80 Gy; n = 18). A control group of 115
      rectal cancer patients who received no irradiation prior to radical surgery was
      used for comparison (group C). The rate of sphincter-saving resection was 71% in
      group A, 61% in group B, and 42% in group C (group A vs. group C; p < 0.0001).
      The local recurrence rate at 5 years was 10% in group A, 6% in group B, and 26%
      in group C (group A vs. group C; p = 0.005). The 5-year survival rate was similar
      among the three groups. These results suggest that preoperative HDRIBT
      contributed to the improvement of local control but not to survival after radical
      resection of rectal cancer. The application of HDRIBT might be useful to restore
      intestinal continuity for rectal cancer.

PMID- 9778937
TI  - Performance of various X-ray film/screen systems in demonstrating small simulated
      low-density lung nodules.
AB  - A high-quality, conventional chest radiograph should be obtained in lung cancer
      screening programs to efficiently detect the faint, small nodular shadows due to
      early lung cancer in the lung fields, although, it is difficult to image the
      entire lung field within the linear part of the characteristic curve of the
      screen/film system owing to the wide variation in tissue density in the thorax,
      which ranges from the well aerated lung superimposed on the intercostal spaces to
      the lung area superimposed on the heart or diaphragm. In the detection of early
      cancer in the lung fields, it is important to consider the very low density (CT
      values of nearly -600 HU to -300 HU) commonly exhibited by early adenocarcinomas
      in the lung. The detectability of such nodules would be greatly influenced by the
      contrast and noise characteristics of the photographic system, the complexity of
      anatomical structures around the nodule, the characteristics of the observation
      system for x-ray films, the interpreter, and so on. The choice of x-ray
      film/screen system basically determines the efficacy of screening; specifically,
      the contrast characteristics of x-ray films together with noise level, which
      varies at different optical densities, affect the detectability of nodular
      shadows. The present study was carried out to determine the most suitable
      sensitometric characteristics and to assess the effects of the noise level of the
      x-ray film/screen system on the detectability of nodular shadows within the lung
      fields, particularly in low-density areas.

PMID- 9778938
TI  - [Schedule of stereotactic radiotherapy: a study considering the factors of repair
      and cell proliferation].
AB  - Stereotactic radiosurgery (SRS: stereotactic irradiation [STI] delivered in a
      single high dose) was initially developed by Leksell for non-malignant brain
      lesions, but there has been increasing interest in using it to treat small
      primary brain tumors or metastases. Recently, stereotactic radiotherapy (SRT:
      fractionated STI) has been recommended on the basis of radiobiological
      considerations for tumors in which both normal glial cells and tumor cells reside
      within the tumor margin. Strangely, the factors 'repair' and 'cell proliferation'
      have been neglected in the radiobiological evaluations of STI reported so far,
      mainly because of the complexity of the calculations. 'Half-time repair' which is
      the key value in the 'repair' factor may be larger for nervous tissue than for
      many other normal tissues because nerve cells have decreased ability to recover
      from damage. 'Cell proliferation' should be an important factor when the total
      radiation period is extended by applying SRT. In this study, we created models
      based on estimated 'half-time repair' and 'cell doubling time' and attempted to
      determine optimal SRT schedules. When repair and cell proliferation factors are
      also taken into consideration, the recommended SRT schedules would be 7 Gy x 7
      fractions every other day for malignant tumors and 3.5 Gy x 12 fractions every
      other day for benign tumors. However, clinically, these schedules should be
      modified according to factors in individual cases, e. g., tumor size, presence of
      tumor necrosis, the patient's general condition, prognosis, and so on.

PMID- 9778939
TI  - [A trial to reduce cardiac motion artifacts on HR-CT images of lung with combined
      use of subsecond scan and a high temporal resolution reconstruction algorithm].
AB  - PURPOSE: To reduce cardiac motion artifacts with combined use of subsecond CT
      scanning and a high temporal resolution algorithm. SUBJECTS AND METHODS: Scan
      data were obtained with step-by-step scanning (scan time, 0.8 seconds). Two sets
      of images were reconstructed, with and without high temporal resolution
      reconstruction algorithm (HTRR), from the same set of scan data. HTRR, derived
      from modification of 180-degree linear helical interpolation, reduces full width
      at half maximum (FWHM) to half of the scan time. Motion artifacts of two sets of
      images were compared. RESULTS: The use of HTRR seemed to be useful in reducing
      cardiac motion artifacts owing to the improvement of effective time resolution.
      However, there were some images without significant reduction of cardiac motion
      artifacts. CONCLUSION: Our technique is useful in reducing cardiac motion
      artifacts without an increase in radiation exposure.

PMID- 9778940
TI  - [Dynamic magnetic resonance dacryocystography using half Fourier single shot fast
      spin echo sequence].
AB  - Dynamic magnetic resonance dacryocystography (MRD) was implemented using 1.5T
      superconductive imager with a standard head coil. Prior to MRD, a pair of
      polyethylene microcatheters were inserted into the lower lacrimal canaliculi.
      Injecting a mixture of 6 ml of saline and 4 ml of xylocaine (0.5%) as a
      substitute for contrast medium, repeated measurement of thick section heavily T2
      weighted image using half Fourier single shot fast spin echo (SSFSE) sequence was
      performed. MRD could well depict the pathologies of the lacrimal sac and the
      lacrimal duct in five cases of epiphora. It pinpointed the level of lacrimal duct
      obstruction, which was confirmed by both X-ray dacryocystography and
      intraoperative findings. Dynamic MRD is a reliable method of diagnosing
      nasolacrimal duct obstruction without using ionizing radiation or chemical
      contrast medium.

PMID- 9778941
TI  - [Reduction of helical artifact using SmartHelical algorithm].
AB  - Stair-step artifact is a serious problem in reconstructed images of multiplanar
      reformation (MPR), surface rendering and maximum-intensity projection (MIP). We
      developed a new algorithm, SmartHelical Algorithm (SHA), to reduce helical
      artifacts. SmartHelical Algorithm reduced helical artifacts significantly with
      slight worsening of longitudinal resolution. Noise was reduced and SNR was
      increased. SHA reduced stair-step artifact in reconstructed images of MPR,
      surface rendering and MIP, and improved image quality.

PMID- 9778942
TI  - [Experimental studies of the protective effect of deferoxamine mesilate on
      cisplatin induced toxicity].
AB  - Cisplatin (CDDP) is an antitumor agent against several types of neoplasms. It
      has, however, various side effects such as nephrotoxicity and ototoxicity.
      Several efforts have been made to prevent these toxic side effects. On the other
      hand, deferoxiamine mesilate (DFO), an iron-chelating agent, has been used for
      iron-overloaded patients. Since the 1980s, many authors have reported DFO
      associated hearing impairment. Some experimental data suggest that DFO itself was
      responsible for ototoxicity. In addition, it has also been recognized that DFO
      can act as a free radical scavenger. Experimental trials using DFO are also
      expected to prevent CDDP-induced toxicity because its generation mechanism is
      thought to be associated with free radical formation. The present study was
      planned to investigate whether DFO, which might be an ototoxic agent, had a
      protective effect against various CDDP-induced toxicities including ototoxicity.
      Fisher rats were used in this study and were divided into four groups: 1) Group
      I, a vehicle control, 2) Group II, animals receiving 100 mg of DFO per kg, 3)
      Group III, animals administered 0.9 mg of CDDP per kg alone and 4) Group IV,
      animals receiving 100 mg of DFO per kg 60 min before 0.9 mg of CDDP per kg for 10
      days. First, the protective effect of DFO against CDDP-induced ototoxicity was
      studied. The auditory threshold was determined by using the compound action
      potential (CAP) from the round window membrane. CAPs were recorded on the 5th day
      after completion of drug administration. Then CAPs recording, cochlear sensory
      epithelia were observed over all the turns of the cochlea by scanning electron
      microscopy. There were no significant differences in CAP thresholds between Group
      I and IV, though the thresholds in Group III were significantly higher at 16 kHz
      and 20 kHz than those in Group IV. The rate of missing outer hair cells in Group
      IV was significantly lower than that in Group III. The results clearly
      demonstrated that DFO had a protective effect against CDDP-induced ototoxicity.
      Second, the protective effect of DFO against CDDP-induced nephrotoxicity was
      studied. Renal function was evaluated by measuring blood urea nitrogen (BUN) and
      serum creatinine (Cr) levels. Both BUN and Cr levels in Group IV were
      significantly lower than those in Group III. The data suggested that DFO
      preadministration prevented CDDP-induced nephrotoxicity. Third, the influence of
      DFO on the antitumor activity of CDDP was investigated in rats inoculated with
      squamous cell carcinoma cells (SCC-131) subcutaneously. The influence of drugs
      was determined by measuring the tumor growth rate. There was no difference in the
      tumor growth rate between Group III and IV. The result revealed that DFO had no
      influence on CDDP antitumor activity. In conclusion, the above results
      demonstrating that DFO preadministration can prevent both CDDP-induced
      ototoxicity and nephrotoxicity without attenuation of CDDP antitumor activity,
      suggest the usefulness of CDDP antitumor chemotherapy.

PMID- 9778943
TI  - [An experimental study of ototoxicity induced by deferoxamine mesilate].
AB  - We investigated the possibility of ototoxicity induced by deferoxamine mesilate
      (DFO). DFO was administered to guinea pigs intraperitoneally at 200 or 400 mg/kg
      body weight/day, 6 days/week for 5 weeks, or 600 mg/kg body weight/day, 6
      days/week for 4 weeks. Physiological saline instead of DFO was given to animals
      as a control. After the course of administration was completed, we measured the
      threshold of the compound action potential (CAP) and the endocochlear potential
      (EP). We also examined the cochlear histology by scanning electron microscopy.
      The CAP threshold of animals treated with 200 or 400 mg of DFO per kg was not
      elevated. In the animals treated with 600 mg/kg , however, the CAP threshold was
      clearly elevated when compared with that of control animals. The EP values of
      animals treated with 200 or 400 mg of DFO per kg were comparable to those of
      control animals. In some animals treated with 600 mg of DFO per kg, however, the
      EP values were decreased. Histological examination revealed that the outer hair
      cells of the cochlea were missing. DFO presumably acts on hair cells, resulting
      in elevation of the CAP threshold. We concluded that hair cell damage is one of
      the contributing factors to CAP threshold elevation.

PMID- 9778944
TI  - [Significance of MIB-1 labeling index and TUNEL labeling index in papillary
      carcinoma].
AB  - Papillary carcinomas, which comprise more than 80% of all thyroid gland cancers,
      are generally regarded as slow-growing tumors with relatively good prognosis.
      Histologically and pathologically, there is a close relationship in papillary
      carcinoma between differentiation and the clinical picture, particularly progress
      and prognosis, However, tumors with the same degree of differentiation may have
      very different growth rates. Therefore, it is important that we have some
      clinical indicator, in addition to differentiation, for projecting clinical
      prognosis, including the likelihood of postoperative recurrence, and for planning
      follow-up care. In this study, we used paraffin embedded specimens obtained from
      40 cases of papillary carcinoma and assessed the proliferative ability of the
      tumor with MIB-1 staining. Moreover, in 28 of the 40 cases we used TUNEL staining
      to study apoptosis in cancer cells, then correlated these two indicators with
      known information about the clinical pathology and prognosis. The degree of
      differentiation and intensity of the MIB-1 labeling index correlated almost
      exactly. Some well-differentiated papillary carcinomas stained heavily with MIB
      1. In fact, in all cases of postoperative recurrence the carcinomas were well
      differentiated, and over half of those showed strong MIB-1 staining. The
      difference between the MIB-1 labeling index for recurring cancers and non
      recurring cancers was statistically significant. In contrast, there was no
      correlation between the TUNEL labeling index and clinical pathology or
      postoperative recurrence. However, in cases of well-differentiated papillary
      carcinoma with anaplastic reversion in the recurrence, the TUNEL labeling index
      was particularly low at the time of the first operation. This indicates that for
      the purpose of patient follow-up, an extremely low TUNEL labeling index may be an
      important piece of information. We also believe that the MIB-1 labeling index is
      another indicator of potential postoperative recurrence.

PMID- 9778945
TI  - [Preoperative examination for estimating the course of the facial nerve].
AB  - In surgery for a parotid tumor, facial palsy is the most serious complication.
      Facial palsy tends to occur in the operation in which the facial nerve runs
      outside of the parotid tumor. Therefore, we developed the facial nerve electric
      stimulating test (FNEST) to determine more accurately the relationship between
      the facial nerve and the tumor. The FNEST diagnosed the condition in half of the
      patients whose facial nerve ran outside of the parotid tumor. Furthermore, a
      combination of CT and FNEST increased the diagnostic efficiency. The FNEST was a
      very efficient preoperative examination for estimating the course of the facial
      nerve.

PMID- 9778946
TI  - [Middle ear mucosa pathophysiology and healing processes in children with otitis
      media with effusion (OME)].
AB  - Most otitis media with effusion (OME) in children heals spontaneously, but it is
      sometimes persistent and intractable. The major factors determining these
      different courses of OME are unknown. Identifying such factors would be
      clinically helpful. Factors affecting on the outcome of OME were studied
      experimentally and clinically. In animal experiment OME was induced in rabbit by
      occluding the Eustachian tube. Clinical study was conducted by investigating a
      histology of the middle ear mucosa, sampled from 64 children with OME (87 ears)
      who underwent middle ear tube ventilation. Furthermore, these cases studied how
      the degree of mastoid pneumatization before and after treatment, changes in the
      volume of the middle ear air cavity and the course after removal of the middle
      ear ventilation tube affected lesions in the middle ear mucosa. In animals,
      histology of the middle ear mucosa showed that in the early stages, the
      subepithelial layer of the middle ear mucosa was characterized by edematous
      hypertrophy and enlarged blood vessels. In later stages, it became fibrous as a
      result of chronic inflammation. These results suggest that lesions of the
      subepithelial layer are unlikely to recover. In clinical cases, histological
      changes in mucosal samples were rated on a two-point scale: changes in the
      epithelium and changes in the subepithelial layer. Re-pneumatization, a sign of
      healing of middle ear mucosal inflammation, was seen 12 months to 18 months after
      surgery. Among patients in whom the tube was left inserted for more than 18
      months, only 11% had unfavorable outcomes and the recurrence rate was low. All
      patients who had recurrence of disease despite more than 18 months of tube
      insertion had prolonged inflammation in the middle ear mucosa. There results
      indicate that the air cavity returns to approximately normal degree of
      pneumatization more than 18 months after surgery, and that the extent of lesions
      in the middle ear mucosa, especially the subepithelial layer, is closely related
      to the healing of OME.

PMID- 9778947
TI  - ["Direct" indirect training approach to rehabilitation of dysphagia patients--a
      new method for rehabilitation with a feeding-tube].
AB  - The rehabilitation approaches for training patients with dysphagia consist of
      both direct approaches (eating training) and indirect approaches (basic training
      for dysphagia patients without food). On the other side, some recent reports
      revealed that some patients who had had severe dysphagia were improved while the
      feeding approach was with a naso-gastic tube and an oral-esophago feeding tube.
      So we thought that stimulation of these feeding tubes for the pharynx and the
      larynx would produce some useful reactions for dysphagia patients. We developed a
      new method for the rehabilitation of such patients. The technique is the repeated
      insertion of the naso-gastric tube at the time of the swallowing motion, which we
      called the "direct" indirect training approach. Sometimes, other basic training
      procedures for dysphagia patients are admissible. We treated 26 patients by this
      method. The patients included those with disorders of the corticobulbar tract (n
      = 11), a disorder of the medulla (n = 5), a disorder of the peripheral nerve (n =
      7), and a long-lasting disused state (n = 3). Twenty-four patients were improved
      and could eat orally without major problems. Laryngeal elevation curves of this
      approach in the pre- and post-therapeutic states revealed that the threshold of
      the swallowing reflux was lower, and the swallowing actions were changed
      dynamically, and became more useful.

PMID- 9778948
TI  - [Evaluation of nasal obstruction with acoustic rhinometry: a simulated study with
      a nasal model].
AB  - The measurement of nasal resistance is important for understanding the
      pathophysiology of nasal obstruction. However, it is difficult to define the
      normal range of nasal resistance because of various physiological factors.
      Several authors have reported that nasal resistance is not correlated with the
      sensation of nasal obstruction. On the other hand, acoustic rhinometry was
      introduced by Hilberg et. al. (1989) to determine the geometry of the nasal
      cavity. The method based on sound reflection analysis provides an estimate of the
      cross-sectinal area of the nasal cavity as a function of the distance from the
      nostril. Recently, the measurement by acoustic rhinometry is becoming popular
      also in our country. However, the assessment by acoustic rhinometry may be
      different from that by measuring nasal resistance because the cross-sectional
      area is measured without studying the air flow. The aim of this study was to
      investigate the benefit of acoustic rhinometry using a nasal model. First, 4
      pieces of nasal model LM005 (KOKEN, Co., Japan) made of silicone were coated with
      resinous putty. Then, the changes in the area-distance curve were measured with
      an acoustic rhinometer RHIN 2100 (SRE, Co., Denmark) in which this putty was
      scraped off gradually from anterior to posterior. In the next study, the quality
      of coated putty was increased at three points of the nasal area: anterior part,
      middle part, and posterior part. Thereafter the changes in the area-distance
      curve were observed in the same way. As a result, neither a decrease or an
      increase in the putty changed the area-distance curve at the posterior part.
      Therefore, it is suitable that the degree of the changing of nasal mucosa is
      defined as the change in the nasal volume between the top the I-notch and the end
      of the C-notch. In conclusion, acoustic rhinometry is useful to investigate nasal
      obstruction, especially the change in the nasal mucosa. Therefore, further
      clinical study is required for the different purpose of measuring nasal
      resistance.

PMID- 9778949
TI  - [Proliferative potential of the ear drum in the process of gerbiline
      cholesteatoma formation].
AB  - Mongolian gerbil frequently develop spontaneous cholesteatoma. As we reported
      previously, in the process of gerbiline cholesteatoma formation, effusions inside
      the pars flaccida are always found in the ears during the early stage, and
      epidermal growth factor (EGF) is also localized in the pars flaccida, especially
      in the mucous layer. In this study, to clarify the process of gerbiline
      cholesteatoma formation, we studied 22 gerbiline temporal bones by using a
      monoclonal antibody against bromodeoxyuridine (BrdU). BrdU-labeled cells
      demonstrate a proliferative potential. We also used a carbon dye method to label
      the micro-vase in 14 gerbiline temporal bones. Cells showing BrdU uptake were
      more abundant, as demonstrated immunohistochemically, in the pars flaccida of
      ears with early cholesteatomas than in the pars flaccida of normal ears (p <
      0.01). The pars flaccida of ears with early cholesteatomas showed hypertrophy of
      both epithelial layers, and hyperkeratosis of the epidermal layer. BrdU-labeled
      cells in the pars flaccida were more localized in the mucous layers than in the
      epidermal layers. In contrast, in ears with cholesteatomas, BrdU-labeled cells
      were less abudant than in ears with early cholesteatomas. In addition, BrdU
      labeled cells in the pars tensa and external auditory epidermal layers were not
      increased in ears with any stage of cholesteatoma formation. We used a carbon dye
      method to detect the micro-vasa in the intermediate layer of the ear drum. Carbon
      dye-labeled vasa were more numerous in the pars flaccida with early
      cholesteatomas than in the pars flaccida of normal ears or ears with
      cholesteatomas. It is highly suspected that angiogenesis was stimulated in the
      pars flaccida with early cholesteatomas, because stimulation of angiogenesis by
      EGF has been reported. The above findings suggest that the mucous layer of the
      pars flaccida has the greatest proliferative potential in the process of
      cholesteatoma formation. Angiogenesis in the pars flaccida appears to be a
      reaction to proliferative changes in the mucous and epidermal layers. These
      changes are probably stimulated by effusion inside the pars flaccida.

PMID- 9778951
TI  - [Pharmacotherapy in the elderly--pharmacokinetic and pharmacodynamic
      considerations].

PMID- 9778950
TI  - [Role of adhesion molecules in tonsillar focal infection].
AB  - Pustulosis palmaris et plantaris (PPP) is a pustular skin disease that is closely
      related to tonsillar focal infection. Patients with this skin disease have shown
      marked improvements of skin lesions after tonsillectomy. In this study, we
      evaluated the role of adhesion molecules in the pathogenesis of tonsillarfocal
      infection related to PPP. The results were that tonsillar lymphocytes of patients
      with PPP adhered to vessels in the dermis, to vessels running through the dermal
      papilla, and to vessels in the epidermis at the base of pustules. The adhesion of
      tonsillar lymphocytes to endothelial cells were significantly blocked by anti-LFA
      1 antibody. An immunohistological study revealed that cells infiltrating the
      dermis expressed LFA-1, whereas ICAM-1, the ligand of LFA-1, was detected on
      endothelial cells and keratinocytes. It is interesting to note that cells
      infiltrating the dermis of the erythema stage or the pustule stage of PPP
      expressed ICAM-1, and the vessels in these stages expressed E-selectin. ICAM-1
      was also detected on vessels in the dermis of skin that seemed to be
      macroscopically normal. These results suggest that tonsillar lymphocytes may have
      an affinity for the skin of PPP-expressing adhesion molecules such as LFA-1, ICAM
      1, and E-selectin. These adhesion molecules seem to be easily activated, not only
      in skin lesions of PPP, but also in macroscopically normal areas resulting in
      cellular infiltration and pustule formation.

PMID- 9778952
TI  - [Stress proteins: biological function and clinical significance].

PMID- 9778953
TI  - [Prevalence of dementia and its subtypes in a rural area in Japan].
AB  - The prevalence of dementia in Japan in 1985 for people aged 65 years or older was
      4.8%. Vascular dementia (VD) has been reported to be the commonest subtype A
      report from Tokyo in 1970 showed that it was 2.8 times more frequent than
      Alzheimer type dementia (SDAT). We assessed the prevalence of dementia in a rural
      area (population: 12,931, 25.3% were 65 years or older in 1994) in Kyoko. First,
      we questioned subjects about their demographic circumstances, memory disturbance,
      apraxia (agnosia) and daily activities. Our questionnaire was answered by 3.132
      (95.8%) subjects, and 2,280 of them agreed to be examined by neurologists. Those
      who met the appropriate criteria of the DSM-III-R and NINCDS-ADRDA were diagnosed
      with dementia. By use of the Hachinski ischemic score (HIS), we distinguished VD
      from non-vascular dementia. In this study patients with non-vascular dementia
      were diagnosed with SDAT by the neurologists. Analysis of the data revealed that
      4.8% of the study population was demented. According to the HIS results, only 3
      of 15 had vascular dementia. The prevalence of dementia was the same as the
      average prevalence in Japan even though the elderly population of this town was
      twice as high as the average. It is hard to determine the prevalence of dementia
      in any community. Many factors must be taken into consideration: the coverage
      rate, the criteria for dementia, and whether to include institutionalized
      residents. The prevalence of dementia will increase with the aging of the
      population, and we must collect accurate data in order to plan efficiently.

PMID- 9778954
TI  - [The new colorimetric assay (WST-1) for cellular growth with normal aging and
      Alzheimer's disease].
AB  - A new tetrazolium compound, WST-1, a sodium salt of 4-[3-(4-iodophenyl)-2-(4
      nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate, was introduced into
      clinical chemistry. The compound's dehydrogenase activities are useful in the
      colorimetric determination of the bioreducibility of cells. It proved to have a
      sensitivity similar to MTT, and produces a highly colored formazan dye under
      reductive conditions. Compared with the MTT assay, we found the WST-1 assay to be
      more sensitive, more convenient, and more exact. We used the new assay to study
      aging-related changes in human lymphocyte blastformation. Four groups of healthy
      adults aged 40-49 years (N = 40), 50-59 years (N = 40), 60-69 years (N = 40), 70
      76 years (N = 40) were examined. Moreover, we studied lymphocytes from 16
      patients (47-74 years) with probable Alzheimer's disease. For healthy controls, a
      negative correlation (r = -0.3108, p < 0.05) between age and enzyme activity was
      noted. The regression equation was: Y = -0.0085X + 1.473 where X and Y designate
      the age of the individual and enzyme activity (absorbance), respectively. On the
      other hand, for patients with Alzheimer's disease, age and enzyme activity did
      not correlate. These results indicate that the WST-1 assay may be useful in the
      study of changes associated with aging, and also more so than the MTT assay.

PMID- 9778955
TI  - [Usefulness and problems of percutaneous endoscopic gastrostomy in a geriatric
      hospital].
AB  - Usefulness and problems of percutaneous endoscopic gastrostomy (PEG) placement in
      a geriatric hospital where most patients were severely demented or bed-ridden
      were evaluated. The variables examined were acute complications, chronic
      complications, restraint of patients before and after PEG placement, change in
      physical activity, and ability of oral intake. Results showed that both acute and
      chronic complications were not rare, but these problems are not peculiar to
      geriatric hospitals. Quality of life (QOL) was clearly improved. Restraint could
      be reduced or stopped in 65.2% of restrained patients after PEG tube placement,
      activity was improved in 55.5% of patients, and oral intake became possible in
      14.0% of patients. There were also some improvements in the management of PEG, as
      the incidence of self-extubation decreased, and tube exchange became easier. In
      conclusion, it is possible to insert and manage the PEG tubes even in geriatric
      hospitals, and PEG tubes are quite useful in managing patients with chronic
      disease and in improving QOL.

PMID- 9778956
TI  - [Nutritional intake by the oldest elderly Japanese. Tokyo Centenarian Study 6].
AB  - Rapid demographic aging has made caring for the elderly an increasingly important
      social issue in Japan. To study current conditions of the oldest elderly
      citizens, we investigated the dietary practices of centenarians in the Tokyo
      metropolitan area. First, we compared the food intake of centenarians with that
      of octogenarians. Next, to identify dietary trends, we investigated whether food
      intake by centenarians had changed significantly between 1981 and 1995.
      Nutritional intake by the centenarians and octogenarians in 1995 was about 60%
      and 75% that of the control, respectively. However, the nutritional intake of
      well nourished centenarians was similar to that of the octogenarians. Cognitive
      function and daily activity have an influence on nutritional intake. The
      centenarians were similar to the control subjects in their consumption of dairy
      products, sweets, and fruit. However, their intake of cereals, meat, fish, and
      fatty oils was loss than 60% that of the control, which indicates their
      preference for soft and sugary foods. The pattern of dietary practices of
      centenarians in 1981 was similar. Although the total food intake of centenarians
      amounted to 60% of the control in 1995 energy intake per kilogram of body weight
      averaged over 30 kcal. As to dietary trends, centenarians in 1981 are more
      cereals, eggs, algae products, and legumes than did their 1995 counterparts. This
      finding seems to reflect a generational difference in dietary habits.

PMID- 9778957
TI  - [Enterohemorrhagic Escherichia coli O157 infection in an elderly patient with
      secondary hemolytic uremic syndrome who developed recurrent acute exacerbation of
      chronic cholecystitis].
AB  - We encountered a patient with enterohemorrhagic Escherichia coli (EHEC) O157:H7
      infection and secondary hemolytic uremic syndrome (HUS). The patient was a 79
      year-old woman with hypertension, constipation, and asymptomatic cholelithiasis.
      She complained of nausea and abdominal pain, and had bloody stool EHEC O157 was
      detected by fecal culture. The bloody stool resolved after treatment with
      antibiotics, but the patient was hospitalized on July 23, 1996 because of
      abdominal distention. HUS was diagnosed because of proteinuria, hematuria,
      thrombocytopenia, hemolytic anemia, fragmentation of red blood cells, and
      increased serum LDH. Treatment was focused on plasma exchange, administration of
      antibiotics, large doses of gamma-globulin, haptoglobin replacement, and
      anticoagulation. Within about 2 weeks, the level of hemoglobin, the number of
      platelets, and the serum LDH had normalized, and the patient recovered from HUS.
      The decreased intestinal movement continued. On August 23, acute cholecystitis
      was diagnosed, and percutaneous transhepatic gall bladder drainage was done.
      Another exacerbation was noted on October 13, and cholecystectomy was done on
      November 12, when the patient's status had improved after instillation of
      antibiotics. Macroscopically, the gallbladder wall was thickened.
      Histopathological examination showed diffuse infiltration of lymphocytes into the
      mucosa, chronic cholecystitis was diagnosed. Because the postoperative course was
      satisfactory, the patient was discharged from the hospital on December 15. Acute
      exacerbation of chronic cholecystitis might have been caused by decreased cholic
      excretion after the marked decrease in intestinal movement due to O157 infection
      and secondary HUS. Because elderly people frequently have anamnesis of the
      digestive system, considerably attention should be paid to the management of
      anamnesis, as well as O157 infection and secondary HUS.

PMID- 9778958
TI  - [An elderly patient with an insulinoma who had prolonged dementia-like symptoms].
AB  - A 77-year-old woman had suffered from memory disturbance and disorientation for
      two years before she was admitted to the hospital because of confusion. Her score
      on the Hasegawa dementia scale revised (HDS-R) was 12 points at the time of the
      first medical examination. No other abnormalities could be found except for a
      blood glucose concentration of 34 mg/ dl. A Magnetic Resonance Image (MRI) of the
      brain showed some small lacunae on both sides in the frontal white matter and
      basal ganglia. After hospitalization, glucose was administered and the blood
      glucose concentration increased, but the dementia-like symptoms did not resolve.
      She was discharged because the symptoms were too difficult to control in the
      general hospital. Although dementia-like symptoms were present even after
      discharge, they did not necessarily appear during fasting. Six months later she
      was rehospitalized. The insulin-blood sugar ratio was at least 0.3 and abdominal
      echogram showed a 1-cm tumor at the tail of pancreas. The pancreas tail was
      removed and the tumor cells were reacted with anti-insulin-antibodies. One month
      after the operation, the dementia-like symptoms had resolved. The HDS-R score was
      improved to 27 points (normal range) 40 days after the operation. The amount of
      the slow waves in the electroencephalogram decreased 5 months after the
      operation. The dementia-like symptoms observed in this case could be regarded as
      the Durchgangssyndrom of Wieck. This syndrome is observed transiently at the time
      of recovery of deterioration of disturbances of consciousness. But it is
      treatable. This patient was an interesting case that showed Durchgangssyndrom
      mimiking dementia associated with insulinoma.

PMID- 9778960
TI  - [A promising program for public health and medical science in the Russian
      Federation].

PMID- 9778959
TI  - [Slowly progressive IDDM with rheumatoid arthritis and Hashimoto disease in high
      elderly].
AB  - We report a 79-year-old woman case of slowly progressive IDDM (SPIDDM) with
      rheumatoid arthritis (RA) and Hashimoto disease. High titer of anti-glutamic acid
      decarboxylase antibody (GAD) with a value of 16,400 U/ml (normal value: less than
      5 U/ml) and deteriorated secretion of insulin, and clinical course led to the
      diagnosis of SPIDDM. Both anti-islet cell and anti-insulin antibodies were
      negative. One year prior to the diagnosis, at 78 years of age, she was newly
      diagnosed with NIDDM and had been medicated with sulfonylurea and voglibose,
      resulting her glucose levels well-controlled. Four months before admission, a
      gradual increase of plasma glucose was noticed, while oral hypoglycemic agents
      were fully administrated. On admission, her glycemic control was revealed as
      follows; a fasting blood glucose level of 458 mg/dl and an HbA1 C level of 14.3%.
      Urinary CPR was 22.5 micrograms day. Her insulin secretion was proved not to be
      induced with intravenous glucagon injection. Hyperinsulinemic euglycemic glucose
      clamp test showed the normal glucose uptake ratio; 9.5 mg/kg/min. Moderate doses
      of subcutaneous insulin (20 units daily) were effective on her diabetes control.
      She was newly diagnosed with Hashimoto disease that required thyroid hormone
      replacement 50 micrograms per day after having developed NIDDM. High titer of
      anti-thyroglobulin antibody (46.9 U/ml) and anti-thyroid peroxidase antibody
      (81.5 U/ml) were observed. The patient had been medicated for RA with anti
      inflammatory drugs since her early seventieth. Rheumatoid factor was elevated to
      127.7 IU/L and, anti-nuclear antibody (x 80) and anti-DNA antibody (x 80) were
      present. It may be of interest that a specific phenotype of HLA; A24 (9) and DR9
      recognized to be susceptible to IDDM was detected in the high-elderly onset
      SPIDDM. Taken together HLA typing with her history of both RA and Hashimoto
      disease, our case may provide the information to the mechanism of pathogenesis of
      SPIDDM. Furthermore, to out knowledge, this is the first case of SPIDDM in the
      aged; 75-year-old or more.

PMID- 9778961
TI  - [Concept of development of public health and medical science in the Russian
      Federation].

PMID- 9778962
TI  - [Status of staff policy and priority tasks of the Ministry of Health of the
      Russian Federation on its improvement in accordance with the Concept of
      Development of Public Health and Medical Science in the Russian Federation].

PMID- 9778964
TI  - [Problems of public health in the State Report on Health Status of the Population
      of the Russian Federation].

PMID- 9778963
TI  - [Approaches to determining the staff policy in public health: international
      experience].

PMID- 9778965
TI  - [Trends in population health status according to data of sociological research].
AB  - Sociological study showed that 67.5% of respondents assessed their health status
      as satisfactory, 22.7% as poor, and 9.8% as good or quite satisfactory. Men are
      three times more often satisfied with their health status than women, and women
      almost three times more often consider their health poor. The characteristics of
      good health decreased almost twofold (1.9) over the last decade, this value for
      women is 2.8 times, while the values indicating deterioration of health status
      notably increased. In general, poor health is 1.7 times more frequent, judging
      from respondents' estimations. Self-assessment of the health status depends on
      respondent's age, education, and social status. The respondents consider that
      medical care should be free of charge and available. Only 4.7% of respondents
      admit paid care as regards additional specialized service, 92.7% of respondents
      wish to be free to select their doctor.

PMID- 9778966
TI  - [Correlation-regression analysis of infant mortality].
AB  - Correlations between neonatal mortality coefficient and a group of socioeconomic
      and ecological parameters are analyzed for some economic regions and districts of
      Russia. At the level of regions, the strongest correlations were observed between
      birth rates, maternal mortality, subsistence minimum, level of education,
      incidence of narcomania and toxicomania (including that among adolescents),
      release of hard harmful substances in the atmosphere and of chlorine and sulfates
      in surface water bodies (r = 0.4-0.8). Multifactorial model was derived by the
      step regression method. This model can be used for predicting the level of
      neonatal mortality in the nearest 5.6 years on the basis of the negative or
      positive shifts in the socioeconomic status of Russia. In addition, several
      unifactorial exponential models at a district level were obtained, reflecting the
      relationship between neonatal mortality and birth rates, unemployment and
      incidence of narcomania and toxicomania.

PMID- 9778967
TI  - [Characterization of medical activities of urban families in raising a healthy
      child].
AB  - Ten statistically significant factors of risk of frequent diseases of children
      have been distinguished; four of them directly reflect medical activity of
      parents: late application for medical care when a child falls ill, neglect of
      prophylactic visits to doctors, neglect of child's health fortification, and
      refusal to take a sick leave when the child is ill. Poor medical activity of
      families as far as it concerns the upbringing of a healthy child results in a
      higher insurance risk, which should be taken into consideration when developing
      legal and economic aspects of medical insurance.

PMID- 9778968
TI  - [Socio-demographic aspects of the problems of refugees in the North].
AB  - Analysis of migration processes in the Arkhangelsk region indicates that the
      demographic, social, and ethnic status of refugees and forced immigrants to the
      North is extremely unfavorable for adaptation. This group is to be regularly
      followed up by physicians, so that the whole armory of immunocorrecting drugs,
      vitamins, and general tonics of animal and plant origin be used for facilitating
      adaptation.

PMID- 9778969
TI  - [Current concepts of economic interrelationships in the public health system].

PMID- 9778970
TI  - [Problem of protection of rights in the area of health and welfare of children
      and adolescents].
AB  - The purpose, principles, and tasks of state social policy concerning the
      protection of health and rights of children are discussed with due consideration
      for the international and Russian legislation. The results of sociological study
      of heads of pediatric institutions are analyzed within the framework of the draft
      law "On Patient's Rights". Proposals on the introduction of an intersectoral
      approach to solution of problems of childhood are validated. The society and
      population at large should take an active part in this process. Suggestions on
      improving the social and legal activity of primary health care system are
      offered.

PMID- 9778971
TI  - [Preliminary results of an evaluation of the effectiveness of general
      practitioners' work].
AB  - Results of comparative assessment of the activities of outpatient health centers
      and general practitioners' activities in the town of Kemerovo are presented.

PMID- 9778972
TI  - [Conceptual substantiation of the application of the systems approach to
      assessment of the quality of medical care].
AB  - A model of the activity of a treatment and prophylactic institution under
      conditions of marketing economy is proposed. This model helps realize the method
      of a total-systems approach to assessing the quality of medical care.

PMID- 9778973
TI  - [Main positions with respect to the formation of the planning and norm-setting
      basis of medical provision].
AB  - Concept on the formation of the design and norm-setting basis of medical service
      has been developed in order to improve planning and balance between the scope of
      rendered services and their financial provision.

PMID- 9778975
TI  - [Development of curriculum at the Medical Faculty of the Moscow University during
      the period of preparing the Code of 1835. 1. Events of 1825-1828].

PMID- 9778974
TI  - [Provision of information on the activities of the State Sanitary-Epidemiologic
      Service].
AB  - Use of a multi-level automated information system has been scientifically
      validated for the State Sanitary Epidemic Surveillance Service of the Russian
      Federation in recent years. Such a system ensures rapid collection, processing,
      and analysis of information on the sanitary and epidemic status of the
      population, activities of sanitary and epidemiological institutions, prediction
      and simulation of sanitary epidemic situations, management of the service. It
      helped automate the routine processes of professional, financial, and managing
      activities of the service institutions.

PMID- 9778976
TI  - [Financing of public health institutions in Byelarus in the 1920's].

PMID- 9778977
TI  - [Social-hygienic characterization of the family and its role in the formation of
      a child's health].
AB  - Discusses the sociohygienic, biomedical, and sociodemographic characteristics of
      families in the down of Vologda. Based on the data of factor analysis, presents
      the structure of factors affecting the health status of children. Assesses the
      modern status and tendencies of the health status of children in the town and the
      child's life style ina family.

PMID- 9778978
TI  - [Patients' opinions of their health status and the results of medical care].
AB  - Anonymous questionnaires were distributed among patients of treatment and
      prophylaxis inpatient and outpatient institutions in the city of Irkutsk.
      Analysis of responses helped detect the causes responsible for the unfavorable
      initial health status of patients and decreasing the probability of favorable
      outcomes after treatment.

PMID- 9778979
TI  - [Priority trends in the prevention of reproductive health disorders].
AB  - Common biomedical and sociohygienic risk factors leading to disorders of the
      reproductive health indicate that universal approaches to their prevention are to
      be developed. The author discusses primary (mainly social), secondary
      (sociomedical), and tertiary (mainly medical) prevention of the above conditions.
      Realization of these measures aimed at preservation and restoration of the
      reproductive health of a family is intended to solve the problem of proper
      reproduction of healthy generations.

PMID- 9778980
TI  - [Social determination of abortion].
AB  - The problem of artificial abortions is analyzed from a social and hygienic
      viewpoint in order to characterize more profoundly the women who have to abort
      pregnancy. The results demonstrate the social causes of family planning by means
      of abortions under conditions of the North nowadays.

PMID- 9778981
TI  - [Professional military training of women a social-hygienic study].
AB  - The author discusses the process of training of women at a military higher
      institution. The main group consisted of 110 women, future military doctors. The
      control group were 87 men studying at a parallel course. In general women study
      better, the motivation of study and the time course of formation of
      sociopsychological relations are different in men and women, the two groups
      differ by the level and time course of the physiological potential of the
      organism, disease incidence is higher in women and the morbidity structure among
      them is peculiar, and shifts in the immune status are more expressed in women;
      moreover, the "price" of adaptation of women to novel conditions of professional
      training is higher. Improvement of military professional training of women is
      based on the primary prediction of its expected efficacy, using a specially
      developed method.

PMID- 9778982
TI  - [Occupational injuries in agriculture].
AB  - Analysis of the incidence of occupational traumas in agriculture in the Saratov
      region is carried out. The first stage of the study consisted in analysis of
      11,462 cases of occupational injuries, the second was devoted to analysis of
      questionnaires of 610 victims of injuries. Effects of chronohygienic,
      occupational, biological, and psychophysiological factors are detected and the
      relationship between life style and traumatism demonstrated.

PMID- 9778983
TI  - [International classification of diseases (tenth revision)].

PMID- 9778984
TI  - [Laboratory support of the State Sanitary and Epidemiologic Service under the new
      socioeconomic conditions].
AB  - Structural and functional changes in the system of laboratory provision of the
      State Sanitary and Epidemiological Service under modern economic conditions had a
      positive impact on the number and quality of laboratory studies. The concept of
      rearrangement of laboratory service for the period of up to the year 2000 and its
      staff and material provision improved the quality of laboratory work and
      eventually the quality of sanitary epidemiological surveillance at the very first
      stages of its realization.

PMID- 9778985
TI  - [Validation of a medical economic standard (as exemplified by pediatric acute
      cranio-cerebral injury)].
AB  - Socio-hygienic study of children with acute craniocerebral injuries carried out
      in the Kalinin district of St. Petersburg helped distinguish a part of general
      sequence of therapeutic measures in such injuries. This will optimize the
      development of medical and economic standard with due consideration for the
      treatment practice and its relation to medical science.

PMID- 9778986
TI  - [An increase in the effectiveness of outpatient care of patients with kidney
      diseases].
AB  - Organization of medical care of patients with renal diseases in a municipal
      health center is described. The authors demonstrate the efficacy of specialized
      care when it was made available for population. The detection of renal diseases
      improved. Use of modern methods of diagnosis and treatment, day-time hospitals,
      and regular check-ups permit timely comprehensive qualified care of patients with
      renal diseases, prevention of disease progress and chronic development, prolong
      the capable life of young patients, and decrease the incidence of disability.

PMID- 9778987
TI  - [Organization of patient intake at private dental institutions].
AB  - Scientifically-based organization of consultations and treatment of patients at
      dental institutions is proposed, based on the balance between the time spent by
      patients in the queue and the equipment downtime. The proposed organization will
      decrease the total duration of treatment.

PMID- 9778988
TI  - [Medico-social expert evaluation and rehabilitation of patients after
      reconstructive surgery for atherosclerosis of the leg vessels].
AB  - The study was aimed at defining the sociomedical criteria of disability after
      reconstructive surgery for atherosclerosis obliterans of the lower limbs, in
      connection with the creation of Federal Service of Sociomedical Expert
      Evaluations and with the crucial changes in methodological approaches to expert
      evaluations and its functional tasks; one more purpose of the study was to
      outline approaches to sociomedical rehabilitation.

PMID- 9778989
TI  - [Historic aspect in staff development for the emergency medical service in the
      Russian Federation].

PMID- 9778990
TI  - [Main trends in the development of postgraduate training of physicians in the
      Republic of Dagestan].
AB  - Analysis of continuous education of physicians in Dagestan helped the author
      distinguish the main trends in its development. They include development and
      introduction of a system of continuous professional and economic education of
      physicians; improving the planning and prediction of need in advanced medical
      training; development and introduction of a system of control of continuous
      education of physicians; stimulation the introduction of modern equipment and
      technologies in practical medicine; creation of scientific and information
      provision for continuous education of physicians. Special attention is paid to
      introduction of novel didactic systems, information technologies, forms and
      methods of advanced medical training.

PMID- 9778991
TI  - [Curriculum development at the Medical Faculty of Moscow University during
      preparation of the Code of 1835. 2. Iu. Kh. Loder's draft and its fate].

PMID- 9778992
TI  - [Professor Mikhail Iakovlevich Kapustin (1848-1920)].

PMID- 9778993
TI  - [Professor V. K. Anrep (1852-1927)--pages from his biography].

PMID- 9778994
TI  - [Z. P. Solov'ev--a prominent figure in zemstvo medicine].

PMID- 9778995
TI  - [The work of the zemstvo doctor according to the recollections of S. S. Iudin].

PMID- 9778997
TI  - [Suicide prevention for the elderly in Matsunoyama Town, Higashikubiki County,
      Niigata Prefecture: psychiatric care for elderly depression in the community].

PMID- 9778996
TI  - [A study on methamphetamine psychosis in a psychiatric clinic--comparison of
      acute and chronic-type cases].
AB  - This study compares patients with acute methamphetamine psychosis to those with
      chronic methamphetamine psychosis and it investigates how the two groups differ
      in terms of psychosomatic findings, social background, and so on. The subjects
      consisted of 100 outpatients diagnosed at our clinic as having methamphetamine
      induced psychosis over a period of sixteen years (1979 to 1995). Of these
      patients, 73 were of the acute type (currently using the drug or totally
      abstinent for less than 3 months), and 27 were of the chronic type (totally
      abstinent from the drug from 2 to 38 years). Psychosomatic Findings Ninety five
      patients (68 acute-type and 27 chronic-type) were classified into six clinical
      clusters, depending on which of the following states was dominant: paranoid
      hallucinatory state, schizophrenia-like state, short-tempered and impulsive
      state, manic-depression-like state, neurosis-like state, and permanent
      encephalopathic state. In the clinical cluster of paranoid-hallucinatory state,
      all 32 patients were of the acute-type. On the other hand, of those patients in
      the clinical cluster of neurosis-like state, the majority (N = 25) were of the
      chronic-type. Social Background The social background of 99 patients (72 acute
      type and 27 chronic-type) was investigated under the three headings of:
      gangsters, criminal records and broken families. Of 19 patients who are
      gangsters, 18 cases were acute and the remaining case was chronic. Of 64 patients
      with criminal records, 51 were acute and 13 were chronic. Of 24 patients who come
      from broken families, 20 were acute and 4 were chronic. In all of these three
      items, the rate of acute-type patients was significantly higher than that of
      chronic-type patients. Based on the results obtained, the medical treatment and
      the prognosis of the patients, the author refers to preventive measures for
      stimulant-drug abuse.

PMID- 9778998
TI  - [Pharmacology of the GABA receptor functions in the central nervous systems].
AB  - gamma-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the
      central nervous system. GABA receptors have been classified into at least two
      categories, GABA(A) receptors, which are heterogeneous multimeric ligand-gated Cl
      channels, and GABA(B) receptors, which are coupled to G-proteins. GABA(B)
      receptors have not only a physiological role in synaptic transmission, but also
      are important in pathological conditions associated with absence epilepsy,
      cognitive disorders and nociception. This review describes our current knowledge
      of the neuropharmacology and neurochemistry of GABA(B) receptors, including their
      heterogeneity as well as the therapeutic potential of the drugs which interact
      with these sites.

PMID- 9778999
TI  - [Development of antiviral therapeutic agents from traditional medicines].
AB  - Traditional medicines contain various metabolites derived from nucleic acid,
      protein, and lipid metabolism. Some of these specific metabolites may recognize
      the differences between viral and host metabolism resulting in anti-viral
      activity; hence traditional medicines may be useful sources for new antiviral
      agents. Traditional medicines can be cheaply obtained and have been orally
      administered as hot-water extracts. Therefore, they may be used for the
      prophylactic and therapeutic treatment of viral infection by drinking them, such
      as coffee or tea. Here we describe how the antiviral activity of traditional
      medicines was screened in vitro and how their therapeutic antiviral activities
      were verified in vivo, to obtain traditional antiviral medicines that can be
      clinically used. Therefore, we have selected 12 herbal extracts, from more than
      250 herbal medicines, that exhibit therapeutic activities against cutaneous
      herpes simplex virus (HSV) type 1 (HSV-1) infection in mice. Four of the 12
      augmented the therapeutic efficacy of acyclovir (ACV) in mice and showed potent
      anti-HSV activity against infection with ACV-resistant HSV-1 mutants in mice.
      These herbal extracts selectively inhibited viral DNA synthesis and showed a
      different mode of anti-HSV-1 action from that of ACV. They were also effective
      against both recurrent HSV and cytomegalovirus infections, without toxicity. Such
      prophylactic and therapeutic antiviral activities of the traditional medicines
      were verified by the purification of major active compounds. We could show new
      indications of traditional medicines as antiviral agents. Thus, the drinking of
      the extracts, in a daily tea or coffee, may be used for prophylaxis and therapy
      of diseases caused by herpes virus infection and improve the quality of life.

PMID- 9779000
TI  - [Preparation and utility of glibenclamide suppository for hospital use].
AB  - Glibenclamide (GC) is widely used as an oral hypoglycemic drug in the treatment
      of non-insulin dependent diabetes mellitus (NIDDM). Since GC is usually taken for
      a long period, side effects and noncompliance are among the problems. In order to
      solve those problems, we prepared GC suppositories and examined their usefulness.
      Suppositories containing 4, 20, and 40 mg of GC were prepared and examined for
      drug release, drug absorption and blood glucose levels after the rectal
      administration of suppositories in rabbits. In the release test, GC suppositories
      released the drug continuously for 6 hours. The areas under the drug release time
      curve (ADT) of 20 and 40 mg GC suppositories were 3.5 and 6.2 times of 4 mg GC
      suppositories respectively. The plasma concentrations after administration of 4
      and 20 mg GC suppositories showed about the same profiles for 6 hours. After
      administration of 40 mg GC suppositories, the maximum plasma concentration (Cmax)
      was observed at 2 hours. All the GC suppositories showed lower blood glucose
      levels compared with the control. The remainder of the area under the blood
      glucose concentration time curve between the control (RAUC) in the case of 40 mg
      GC suppository was 1.3 times larger than that of the 4 mg GC suppository. The GC
      suppositories sufficiently lowered the blood glucose levels. These results
      suggest that the GC suppositories should be useful in the hospital preparation
      for the treatment of NIDDM patients.

PMID- 9779001
TI  - [Quantitative analysis and pharmaco-toxicity of cannabinoids in commercially
      available cannabis seeds].
AB  - delta 9-Tetrahydrocannabinol (delta 9-THC), cannabinol, cannabidiol and
      cannabichromene were detected in commercially available cannabis seeds by silica
      gel TLC and gas chromatography. These cannabinoids existed in rather high content
      (0.10-2.02 mg/100 g of seeds) in the feed for birds especially bracts (82.3-441
      mg/100 g). When the suspension prepared from the benzene washing solution of
      cannabis seeds, BenW, was administered at a dose of 3 mg/kg corresponding to
      delta 9-THC into a mouse, i.v., BenW caused hypothermia, catalepsy, pentobarbital
      induced sleep prolongation and suppression of locomotor activity. These
      pharmacological activities of BenW were significantly higher than those of delta
      9-THC (3 mg/kg, i.v.). These results may indicate the necessity to reconsider the
      present regulations on marihuana.

PMID- 9779002
TI  - [Inactivation and toxoiding of biologically-active components of Bordetella
      pertussis by tea catechins].
AB  - An ability of tea catechins known as agents for the disinfection to bacteria and
      viruses were tested on application for toxoiding biologically active components
      of Bordetella pertussis. The effects on the activities and antigenicity of
      filamentous hemagglutinin (FHA) and pertussis toxin (PT) were investigated. The
      activities of FHA and PT were inactivated by catechins at approximately 10(3)
      times lower dose (0.2 mM) compared with that of formalin. The activity of
      inactivated FHA was recovered by dialysis against Tris-HCl buffer, pH 8.0,
      containing glutathione or Tris-HCl buffer, pH 6.0. But the activity of
      inactivated PT was not recovered. Antigenicity of catechin-treated antigens were
      investigated by immunization to mice. The sera from mice immunized by catechin
      treated FHA or PT were contained antibody against not only catechin-treated but
      also non-treated FHA or PT. These results suggest that antigenicity of FHA or PT
      was not destroyed by the treatment with catechin. We prepared pertussis-component
      vaccines by treatment of several catechins on the condition that FHA or PT
      activity was not recovered. Higher efficacy were found on the vaccines made by
      treatment of epicatechin, epicatechin gallate, or epigallocatechin than those by
      formalin. The vaccine prepared by using epigallocatechin gallate had significant
      efficacy as well as that by formalin treated one. From these results, it is
      suggested that tea leaf catechins were effective agents for toxoiding of vaccine
      components.

PMID- 9779003
TI  - [Inhibitory effects of natural medicines on the enzymes related to the skin].
AB  - In this paper, we investigated the inhibitory effects of water extracts from
      sixty-six natural medicines on the enzymes related to the skin, which were
      tyrosinase, hyaluronidase and collagenase. To clarify the inhibitory components
      in water extracts, tannin quantity and the inhibitory activity of the water
      extracts after removal of phenolic compounds using polyclar AT, were measured.
      Twelve kinds of natural medicines were found to have tyrosinase inhibitory
      activity. Six of them showed that tannin, which contains sufficient amounts in
      extracts, might be major inhibitory compounds due to a significant decrease of
      inhibition by these samples after removal of phenolic compounds. The inhibitory
      compound of Aurantii fructus immaturus was thought phenolic compounds except
      tannin. The inhibitory compounds may include Armeniacae semen, Perillae folium
      and Persicae semen besides a phenolic compound. Twenty-seven species among the
      natural medicines studied showed inhibitory activity on hyaluronidase. Phenolic
      compounds in these extracts except Artemisiae argyi folium, could not be
      candidates for hyaluronidase inhibitors. Seven kinds of the natural medicines
      have inhibitory activity on collagenase. It was estimated that these inhibitory
      compounds were phenolic compounds. These results are to be expected for finding
      novel compounds for skin disease or skin-care cosmetics.

PMID- 9779004
TI  - [Internal coordination of circadian rhythms and temporal synergism in animal
      adaptive reactions].
AB  - The multioscillatory principle of circadian organization of organism functions is
      based on the ability of some organs and cells to generate independent set of
      oscillations with 24 hours period. Coexistence of two or more independent rhythm
      producers provides a flexible structure of numerous cycles that take place in
      organism. The stable changes of circadian rhythms can be caused either by
      external factors (e.g., seasonal changes of photoperiod, socially determined
      changes of labour regime, cycles of sleep, feeding time) or by some inner
      factors, e.g. stress syndrome or illness. In its turn the changes in phase
      relations between circadian rhythms of some hormones and neuromediators play an
      important role in formation of some adaptive reactions, i.e. seasonal changes in
      reproductive system, peculiarities of lipid metabolism, migration behaviour,
      preparation to hibernation, or the rate of metamorphism in amphibians. These data
      allow to formulate the hypothesis of temporal synergism. According to this
      hypothesis morphophysiological effect caused by joint action of two or more
      hormones or neuromediators is dependent on the phase relationships of their
      circadian rhythms.

PMID- 9779005
TI  - [An error in determining the number of migrants during the trapping of small
      mammals with weighted lines].
AB  - The number of residential animals in daily samples is diminishing regularly
      during prolonged catching. It might diminish according to exponential law if: (1)
      the probability to be captured for each animal living on the sampling territory
      does not alter in the course of trapping; (2) all animals have the same
      possibility to be captured. The number of captured non-residential (migrating)
      animals stays the same during he whole period of trapping, thus increasing the
      number of animal captured at the end of trapping vs. one expected according
      exponential law. It is not correct however to consider the presence of migrants
      to be the only reason of the deviation from exponential decrease, because it is
      observed also in residential animals. (1) Home ranges of some animals overlap the
      trap line only by their edge. The possibility to capture such animals is 2-3
      times lower than animals with central position of home ranges on the trap line.
      (2) The removal of peculiar demographic groups is not equal. Adult females are
      captured with highest intensity; young animals, on the opposite, stay uncaptured
      longer. It may be registered as increasing of proportion of young and subadult
      animals per an adult female with each day of removal. (3) Reproduction is
      intensive in summer. Young animals (up to age of 20 days) does not visit traps.
      Some of them become active in the middle and the end of trapping period when a
      great share of older animals (including their parents) is already captured.
      Because of these reasons disturbed exponential removal exists even in residential
      animals, and we can not differ the real proportion of migrants even in cases when
      the disturbance of exponential decrease per se is proved properly.

PMID- 9779006
TI  - Safer eggs laying the groundwork.

PMID- 9779007
TI  - Critical controls for juice safety.

PMID- 9779008
TI  - Home cookin'. Consumers' kitchens fail inspections.

PMID- 9779009
TI  - Prostate cancer.

PMID- 9779010
TI  - An FDA guide to dietary supplements.

PMID- 9779011
TI  - Shoddy practices shut down oxygen supplier.

PMID- 9779012
TI  - Crab processor shut down for sanitary violations.

PMID- 9779013
TI  - Bribery attempt goes awry.

PMID- 9779014
TI  - The influence of radiographic contrast media on some granulocyte functions.
AB  - Radiographic CM are used to change the X-ray absorption of tissue. They have been
      used since the 1930's and today four main types are available. All these CM are
      derived from one original structure: the 2,4,6 triiodobenzoic acid with the
      substituents in positions 1,2 and 5 as a carboxylic group or amides. According to
      the nature of the substituents and the number of aromatic rings, the four
      different types of CM can be identified. Three of the four types of CM are
      hyperosmolar, some of the ionic CM contain meglumine and all CM contain calcium
      disodium EDTA. To fulfil their role in host defence, circulatory PMN must adhere
      to endothelium of capillaries and venules adjacent to the inflammatory locus,
      migrate through the vessel wall to the area of inflammation, phagocytose
      opsonized bacteria, kill ingested organisms and, finally, inactivate their own
      toxic products to prevent damage to normal tissue. CM should be biologically
      inert, but many physiological and pathophysiological effects have been described.
      This review deals with the present knowledge about the influence of CM on PMN.
      This thesis presents results of the effects of the four main types of CM on PMN
      exocytosis of elastase and lactoferrin, adherence to nylon fibers, chemotaxis
      under agarose and phagocytosis of latex particles, as well after in vitro
      exposure of CM to PMN and after intravascular injection of CM. After in vitro
      exposure of CM to whole blood, a dose-dependent fall in lactoferrin and elastase
      concentration was observed, statistically significant for diatrizoate and
      ioxaglate at high concentrations. I.v. injection of iohexol or ioxaglate resulted
      in small, although statistical, decreases in lactoferrin concentration in plasma.
      No differences between the CM groups were seen. PMN adherence to nylon fibers
      after incubation of CM with whole blood or isolated PMNs was inhibited. The most
      inhibitive agents were the ionic CM diatrizoate and ioxaglate. The meglumine ion
      was found to contribute to the inhibitive effect of diatrizoate upon adherence.
      Following i.v. injection of iohexol or ioxaglate, increased numbers of PMNs, in
      combination with decreased adherence, were noted with ioxaglate, and the opposite
      with iohexol. Immediately after arteriography with iohexol and ioxaglate, a small
      increase of PMN count, in combination with decreased adherence, could be seen. An
      inhibition of adherence will result in a shift from the marginal to the
      circulatory pool of PMNs and thus an increase in PMN count. Although
      statistically significant the changes were minor. A pronounced increase in PMN
      count was seen 2-5 hours after arteriography in combination with a decrease in
      adherence. These changes may be due to a release of glucocorticoids from the
      adrenals in response to the procedure and/or the injection of CM. CMs do not act
      as chemoattractants. However, when CM are added to the chemoattractant N-fMLP in
      the under agarose assay, the number of PMNs migrating (density) was lowered,
      while the distance migrated by the leading front was not affected except for
      diatrizoate that almost abolished migration. When diatrizoate was added to PMNs,
      a dose-dependent inhibition was observed. Following i.v. injection of CM, no
      changes in PMN chemotaxis or changes in the chemoattractive potential of serum
      could be demonstrated compared to the baseline levels. The ability of PMNs to
      ingest latex particles after incubation with CM was inhibited in a dose-dependent
      way. The most inhibitive agents were diatrizoate and ioxaglate. A solution
      containing the same amount of disodium calcium EDTA as the CM solutions inhibited
      phagocytosis significantly, although less than the CM solution. Improved
      phagocytosis was observed in hyperosmolar environments due to NaCl or mannitol at
      osmolarities higher than 369 mOsm. I.v. injection of ioxaglate or iohexol
      inhibited the phagocytosis of latex particles by PMNs. The impairment was most
      pronounced immediately after the injection, and had almost returned to ba

PMID- 9779016
TI  - Cardiac pacing in Canada in 1998: working towards optimal pacing therapy.
      Canadian Working Group on Cardiac Pacing.
AB  - The Canadian Working Group on Cardiac Pacing (CWGCP) was formed in 1996 with the
      primary goal of promoting optimal pacing therapy in Canada. In 1997, the CWGCP
      conducted a survey of pacing practices across Canada. Ninety-two of 125
      implanting programs (74%) responded. Implant rates vary by province--from 39 per
      100,00 population in Ontario to 63 per 100,000 population in Nova Scotia and
      Prince Edward Island. Variations in regional implant rates persist even after
      correcting for the age of the population. Physiological pacing was used for 35%
      of all implants in Canada in 1996/97. There were marked differences across Canada
      in the mode of pacing selected. In western Canada, 39.5% of pacing systems
      implanted were physiological compared with 18.2% in Atlantic Canada and 29% in
      Quebec. There were also differences in follow-up practices. Approximately 40% of
      centres follow patients with single chamber pacemakers annually, whereas most
      other centres still follow these patients every six months. Economic constraints,
      the size of pacing programs and the involvement of committed pacing physicians
      are factors that may influence the regional differences in cardiac pacing across
      Canada.

PMID- 9779015
TI  - Coronary stenting in unstable angina: early and late clinical outcomes.
AB  - OBJECTIVE: To examine the procedural and long term success of coronary stenting
      in patients presenting with unstable angina and the effect of warfarin on the
      clinical outcome of these high risk patients. DESIGN: A nonrandomized,
      retrospective analysis of patients presenting with unstable angina. SETTING: A
      tertiary care, Canadian university-affiliated teaching hospital. PATIENTS: Of
      1250 patients who underwent percutaneous transluminal coronary angioplasty
      between January 1994 and June 1995, 365 underwent coronary stenting. The study
      population consisted of the 156 patients presenting with unstable angina who
      underwent coronary stenting. Patients with Canadian Cardiovascular Society class
      IV and postinfarction angina were included. INTERVENTIONS: Stent delivery by
      standard techniques to the target lesion was successful in all patients. At
      discharge, 88 patients were prescribed warfarin, ticlopidine and acetylsalicylic
      acid (ASA); the remaining 68 patients received only ticlopidine and ASA. Late
      clinical outcomes were assessed by telephone interview. RESULTS: The overall
      procedural success rate was 96%. One patient died in hospital (0.6%). Other
      events were abrupt closure (1.9%), myocardial infarction (1.9%) and urgent bypass
      surgery (1.9%). During follow-up, target vessel reintervention was needed in
      19.6% of patients. Early and late clinical outcomes did not differ significantly
      between anticoagulated patients and those treated with antiplatelet agents alone,
      but anticoagulated patients had a significantly longer hospital stay.
      CONCLUSIONS: Coronary stenting in patients with unstable angina was associated
      with excellent procedural success and favourable late clinical outcomes. Warfarin
      added no apparent additional clinical benefit to antiplatelet agents in this high
      risk population.

PMID- 9779017
TI  - Coronary endarterectomy revisited: mid-term angiographic results.
AB  - OBJECTIVES: To evaluate the value of concomitant coronary endarterectomy (CE) in
      the modern era of coronary revascularization. METHODS: Retrospective study.
      Twenty-eight patients (five women; 23 men) who underwent coronary endarterectomy
      were angiographically studied 24 +/- 22 months after the procedure. Necessity CE
      (vessel completely occluded or with lumen less than 1 mm) was performed on the
      left anterior descending (LAD) artery in 12 patients, the right coronary artery
      (RCA) in nine, the obtuse marginal artery (OM) in five and a diagonal branch in
      two patients. Conduits used for revascularization were the internal thoracic
      artery (ITA) in 11 (all anastomosed to the LAD; combined with saphenous vein
      patch in four) and a saphenous vein graft in 17 patients. Mean atherosclerotic
      core length was 3.3 +/- 1.8 cm. An average of 3.1 +/- 0.7 distal anastomoses per
      patient were constructed, with mean aortic cross-clamp and cardiopulmonary bypass
      times of 61.2 +/- 20.2 mins and 94.0 +/- 23.5 mins, respectively. RESULTS:
      Overall, angiographic patency rate was 71% (20 of 28) for the endarterectomized
      vessels (12 of 12 LAD, six of nine RCA, two of five OM and none of two diagonal
      arteries) and 93% (57 of 61) for the nonendarterectomized vessels. Among the
      eight patients with occluded CE vessels, two sustained a perioperative myocardial
      infarction, five developed angina during follow-up, and one patient remained
      asymptomatic. CONCLUSION: Necessity CE demonstrates acceptable mid-term patency.
      In addition, this study showed excellent patency following CE of the LAD
      revascularized with the ITA, with or without only a saphenous vein patch.

PMID- 9779019
TI  - Ambulatory care training in cardiology: redefining the traditional arena of
      learning.
AB  - Fiscal restraint, consolidation of resources and services, and restructuring have
      led to changes in the case mix of teaching hospitals, which places limitations on
      the education of medical trainees in this environment and has sparked growing
      interest in the teaching of clinical medicine in the ambulatory care setting.
      Early attempts to emphasize ambulatory care in training programs, and the
      strengths and weaknesses of this teaching forum are reviewed, and a model of its
      application to the discipline of cardiology is offered.

PMID- 9779018
TI  - Clinical and pathophysiological effects of active and passive smoking on the
      cardiovascular system.
AB  - Both passive and active cigarette smoking increase the risk of cardiovascular
      disease, the leading cause of death in Western industrialized nations. The
      prevalence of smoking as a major cardiovascular risk factor has been well
      characterized over the past 30 years. The two demographic groups of particular
      concern are women and the young. The relationship between active tobacco smoking
      and increased risk of coronary artery disease (stable and unstable angina, acute
      myocardial infarction or sudden death), cerebrovascular disease (cerebral
      infarction, and cerebral and subarachnoid hemorrhage), peripheral arterial
      disease (large and small vessel) and aortic aneurysm has been well established in
      numerous longitudinal and cross-sectional epidemiological and basic science
      studies. More recently, passive smoking has been shown to represent an important
      risk factor for coronary artery disease. Smoking can elicit both acute and
      chronic cardiac and vascular events due to the multiplicity of mechanisms
      involved: hematological, neurohormonal, metabolic, hemodynamic, molecular genetic
      and biochemical pathways. Smoking cessation can result in both the inhibition of
      progression and the regression of pathophysiological changes, improving morbidity
      and mortality among chronic smokers. The incidence of coronary artery and
      cerebrovascular diseases in former smokers decreases by 50% two to three years
      following cessation, but a small long term excess risk persists. Smoking as a
      cardiovascular risk factor and the clinical cardiovascular features associated
      with active and passive smoking are discussed, and a pathophysiological framework
      to explain the association between cigarette smoking and cardiovascular disease
      is provided.

PMID- 9779020
TI  - Staphylococcus aureus pericarditis with tamponade complicating coronary
      angioplasty and stenting.
AB  - Infectious complications of coronary angioplasty and stenting are uncommon. A 70
      year-old man is presented who underwent percutaneous transluminal coronary
      angioplasty (PTCA) and stenting of an occluded left anterior descending artery.
      This was complicated by Staphylococcus aureus pericarditis with tamponade. He was
      successfully treated with a closed drainage and antibiotics. This is the first
      reported case in the literature that documents purulent pericarditis and
      tamponade following percutaneous revascularization.

PMID- 9779021
TI  - Arterial embolism complicating implantable cardioverter defibrillator shocks with
      normal ventricular function.
AB  - A 69-year-old man developed an embolus to his right femoral artery 24 h following
      the insertion of an implantable cardioverter defibrillator (ICD), with multiple
      shocks administered in the early postoperative period. He had nonobstructive
      hypertrophic cardiomyopathy with normal left ventricular function and no evidence
      of left atrial or ventricular thrombus seen on pre- or postoperative
      transthoracic echocardiography. There was no evidence of atrial fibrillation
      documented before or after implantation of the device. He had no other known risk
      factors for thromboembolic disease. Thromboembolic phenomena as a complication of
      ICD use have been described but arterial emboli believed related to ICD shocks
      have not been reported in patients without impaired systolic function.

PMID- 9779022
TI  - Toxic methemoglobinemia: a rare but serious complication of transesophageal
      echocardiography.
AB  - Cyanosis occurring during a transesophageal echocardiogram (TEE) is usually
      related to the respiratory depressant effect of the administered sedative.
      However, acute toxic methemoglobinemia related to topical benzocaine is a rare
      and not well recognized but potentially life threatening cause of cyanosis during
      or after TEE. A case of this condition is presented and the literature on its
      frequency, diagnosis and management is briefly reviewed.

PMID- 9779023
TI  - Myocardial infarction complicated by ventricular septal rupture in a patient with
      polycythemia vera and minimal coronary ectasia.
AB  - Although it is known that patients with polycythemia vera (PV) are at increased
      risk of myocardial infarction (MI) secondary to thrombosis, ventricular septal
      rupture in this setting has never been reported. Ventricular septal rupture
      complicating a small anteroseptal MI is reported in a patient with PV and with
      only minimal ectasia of the left anterior descending coronary artery. Despite
      small infarct size these patients may be predisposed to myocardial hemorrhage,
      increasing the likelihood of myocardial rupture.

PMID- 9779025
TI  - Clinical training in cardiology.

PMID- 9779024
TI  - Right bundle branch block: a source of error in the Doppler assessment of right
      ventricular pressure in patients with a ventricular septal defect.
AB  - A case is presented in which low right ventricular pressure was calculated
      erroneously from the Doppler-derived velocity of flow through a ventricular
      septal defect. This is thought to be due to the presence of right bundle branch
      block. Reasons for this error and a way to avoid errors in calculation are
      discussed.

PMID- 9779026
TI  - Antithrombotic treatment of acute coronary syndromes.
AB  - This article provides a brief review of the coagulation process and an overview
      of the different antithrombotic treatment strategies that are available or being
      developed for the management of acute coronary syndromes. Active antithrombotic
      agents belong to three general classes: thrombolytic agents, anticoagulants and
      antiplatelet drugs. Thrombolytic agents are life-saving in acute myocardial
      infarction with ST segment elevation, but they are not useful and possibly
      harmful in other acute coronary syndromes. Anticoagulants are very effective
      during the acute phase, but their benefit is limited by reactivation of the
      disease following their discontinuation. Antiplatelet therapy with
      acetylsalicylic acid is useful during the acute, subacute and more chronic phases
      of acute coronary syndromes. The future is rich in treatment opportunities with
      the availability of a new generation of anticoagulants (e.g., low molecular
      weight heparins) and of antiplatelet agents (i.e., glycoprotein IIb/IIIa
      inhibitors).

PMID- 9779027
TI  - Approaches to the treatment of unstable angina and non-Q wave myocardial
      infarction.
AB  - Multiple clinical trials have been undertaken to understand better the events
      leading to unstable angina and non-Q wave myocardial infarction. Some of these
      studies focused on evaluating the role of antithrombotic therapy; others
      evaluated the role of more aggressive invasive treatment versus medical therapy.
      In the 1980s and 1990s, studies revealed that antithrombotic therapy with either
      acetylsalicyclic acid alone or heparin alone was more effective than placebo. The
      Thrombosis in Myocardial Infarction (TIMI) IIIB study attempted to compare
      medical therapy with early surgical intervention, reporting that early
      intervention did not result in any significant improvement in patient outcome
      over medical therapy. In the mid- to late 1990s, the thrombin hypothesis was
      introduced, suggesting that thrombin antagonists would arrest the coagulation and
      thrombotic cascade. The Global Use of Strategies To Open Occluded Coronary
      Arteries (GUSTO) IIb study put the thrombin hypothesis to the test, and it found
      that there was no significant difference between hirudin and unfractionated
      heparin treatments after 30 days. Glycoprotein IIb/IIIa receptor antagonists were
      then researched in the Evaluation of 7E3 for the Prevention of Ischemic
      Complications (EPIC), the c7E3 Fab Antiplatelet Therapy in Unstable Refractory
      angina (CAPTURE), the Platelet IIb/IIIa Antagonism for the Reduction of Acute
      coronary syndrome events in a Global Organization Network (PARAGON) and the
      Platelet Receptor Inhibition of Ischemic Syndrome Management in Patients Limited
      to Unstable Angina Signs and Symptoms (PRISM-PLUS) studies, shifting the
      attention to the platelet. These studies gave contrasting results, bringing to
      the foreground the issues of optimal use of antithrombotic agents and proper
      timing of surgical intervention. Medical therapy for unstable angina and non-Q
      wave myocardial infarction was addressed in the Efficacy and Safety of
      Subcutaneous Enoxaparin in Non-Q-wave Coronary Events (ESSENCE) study, which
      compared a low molecular weight heparin, enoxaparin, with unfractionated heparin.
      A significant difference in outcomes was found in favour of enoxaparin.

PMID- 9779028
TI  - ESSENCE trial results: breaking new ground. Efficacy and Safety of Subcutaneous
      Enoxaparin in Non-Q wave Coronary Events.
AB  - OBJECTIVE: To demonstrate the superiority of enoxaparin compared with
      unfractionated heparin (UFH) in preventing recurrent angina, myocardial
      infarction (MI) and death in patients presenting with unstable angina or non-Q
      wave MI. DESIGN: A prospective, randomized, double-blind multicentre trial.
      SETTING: One hundred and seventy-six centers in 10 countries. PATIENTS: Three
      thousand one hundred and seventy-one patients, male or nonpregnant females, 18
      years of age or older, with unstable angina or non-Q wave MI. INTERVENTION:
      Patients received either enoxaparin 1 mg/kg every 12 h subcutaneously plus an
      intravenous placebo, or subcutaneous placebo injections and UFH as a continuous
      intravenous infusion. All patients received 100 mg to 325 mg of acetylsalicylic
      acid daily. Study treatment was administered for 48 h to 8 days. MAIN RESULTS:
      The primary end-point (recurrent angina, MI or death) was significantly lower in
      the enoxaparin group compared with the UFH group (16.6% versus 19.8%; P = 0.02)
      after 14 days and remained significant after 30 days. The need for coronary
      revascularization was significantly lower for patients assigned to enoxaparin
      (27.0% versus 32.2%; P < 0.01) after 30 days. There was no difference in the risk
      of serious hemorrhage between the two groups, but there was a significantly
      higher incidence of minor hemorrhagic complications in the enoxaparin group
      (11.9%) versus 7.2%; P < 0.01). CONCLUSIONS: Enoxaparin significantly reduced the
      triple end-point of recurrent angina, MI and death at 14 days, with a sustained
      effect at 30 days. There was no increase in the total number of hemorrhages;
      however, a significant increase in the rate of minor hemorrhage was observed.

PMID- 9779029
TI  - Management of acute coronary syndromes with low molecular weight heparin: TIMI
      11A and 11B.
AB  - The role of antithrombotic therapy has been studied in patients with acute
      coronary ischemia without ST segment elevation. Unfractionated heparin (UFH) has
      been found to decrease the rate of myocardial infarction (MI), and to reduce
      overall mortality and recurrent MI in a series of trials in patients with
      unstable angina and non-Q wave MI. UFH is limited due to its unpredictable
      antithrombotic effect, poor bioavailability when given subcutaneously,
      requirement for hospitalization and need for frequent laboratory monitoring.
      Conversely, low molecular weight heparins (LMWHS) offer a number of advantages
      over UFH. LMWHs have a predictable antithrombotic response, good bioavailability
      following subcutaneous administration and longer half-life than UFH, require less
      frequent monitoring than UFH and can be administered in fixed or weight-adjusted
      subcutaneous dosages once or twice daily. The safety and efficacy of the LMWH
      enoxaparin are evaluated in the Thrombolysis in Myocardial Infarction (TIMI) 11
      program. TIMI 11 A was designed to compare the safety and tolerability of two
      dosage regimens of enoxaparin in patients with unstable angina or non-Q wave MI,
      whereas TIMI 11B was designed as a phase III trial, comparing the efficacy and
      safety of enoxaparin with those of UFH in the acute phase, and the efficacy and
      safety of extended administration of LMWH with those of placebo for 45 days. TIMI
      11A found that the rate of major hemorrhage was significantly lower for the lower
      enoxaparin dose (1.0 mg/kg). The results of the published studies indicate that
      LMWHs are effective in reducing major ischemic outcomes in patients with unstable
      angina and non-Q wave MI. The results of the TIMI 11B trial will be available in
      late 1998.

PMID- 9779030
TI  - When innovative therapies make economic sense: economic analysis of enoxaparin
      versus unfractionated heparin in the ESSENCE trial--an overview. Efficacy and
      Safety of Subcutaneous in non-Q Wave Coronary Events.
AB  - An economic substudy using intention-to-treat analysis was conducted
      prospectively to compare the costs of enoxaparin and unfractionated heparin (UFH)
      therapy in 936 patients enrolled in the United States arm of the multicentre,
      international Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave
      Coronary Events (ESSENCE) trial. Hospital billing data were used for 655 of the
      American patients. Hospital costs for the remainder of the patients were imputed
      using a multivariate linear regression model (r2 = 0.86). Physician fees were
      estimated from the Medicare Fee Schedule. Results indicated that, compared with
      UFH patients, enoxaparin patients made use of fewer resources during initial
      hospitalization, with the largest difference in resource use seen for coronary
      angioplasty patients (15% for enoxaparin versus 20% for UFH patients; P = 0.04).
      This trend persisted at 30 days, with the largest reductions in resource use
      occurring in diagnostic catheterization (57% versus 63%, respectively; P = 0.04)
      and coronary angioplasty (18% versus 22%, respectively; P = 0.08). Although the
      mean cost for a course of enoxaparin was US $155, compared with US $80 for UFH,
      total medical costs for hospitalization, physician care and drugs during the
      initial treatment phase were US $11,857 for enoxaparin therapy versus US $12,620
      for UFH therapy, producing a cost advantage of US $763 for enoxaparin therapy (P
      = 0.18). Cumulative cost savings associated with enoxaparin treatment at 30 days
      were US $1,172 (P = 0.04). Results suggested that enoxaparin therapy compared
      with standard UFH therapy improves key clinical outcomes and saves money in
      patients with acute coronary syndrome.

PMID- 9779031
TI  - Low molecular weight heparins: are they different?
AB  - In addition to their use in postsurgical and medical prophylaxis of deep vein
      thrombosis (DVT), low molecular weight heparins (LMWHs) are being developed for
      cardiovascular and cerebrovascular indications. Because of manufacturing
      differences, each LMWH exhibits distinct pharmacological and biochemical profiles
      that may influence clinical performance. The specific activity of these agents in
      anticoagulant assays ranges from 35 to 45 anti-IIa U/mg or 80 to 120 anti-Xa
      U/mg. LMWHs are capable of producing product-specific dose- and time-dependent
      antithrombotic effects in animal models of thrombosis. While the ex vivo effects
      are initially present at antithrombotic doses, these agents have been found to
      produce sustained antithrombotic effects without any detectable ex vivo
      anticoagulant actions. In experimental animal models and in various clinical
      trials, these agents have also been found to release tissue factor pathway
      inhibitor (TFPI) after both intravenous and subcutaneous administration. Repeated
      administration of LMWHs produces progressively stronger antithrombotic effects.
      However, the hemorrhagic responses vary and are largely product dependent. The
      product-dependent release of TFPI following intravenous and subcutaneous
      administration in a primate model also demonstrates the relevance of this
      inhibitor to the actions of LMWHs. The effect of repeated administration of LMWH
      mimicking the postsurgical prophylaxis of DVT exhibited product-based
      augmentation of the antithrombotic or hemorrhagic effects.

PMID- 9779032
TI  - Low molecular weight heparin in coronary stenting.
AB  - A pilot clinical study called Enoxaparin and Ticlopidine after Elective Stenting
      (ENTICES) was designed to determine whether the combination of enoxaparin,
      ticlopidine and acetylsalicylic acid (ASA) is superior to the conventional five
      drug regimen routinely used after elective stent placement (warfarin,
      unfractionated heparin, dextran, dipyridamole and ASA). Compared with patients on
      conventional therapy (44), those randomly assigned to enoxaparin and ticlopidine
      (79) had a lower composite rate of in-hospital bleeding and vascular
      complications (5% versus 16%; P = 0.005), a significantly lower composite end
      point rate (death, nonfatal myocardial infarction, stent thrombosis of urgent
      revascularization) at 30 days (5% versus 20%; P = 0.001), a significantly lower
      incidence of stent thrombosis in the first 30 days (0% versus 7%; P = 0.04) and
      the same incidence of death or repeat angioplasty at six months. The Antiplatelet
      Therapy versus Lovenox plus Antiplatelet Therapy for Patients with an Increased
      Risk of Stent Thrombosis (ATLAST) trial was subsequently designed to compare the
      efficacy of the combination therapy enoxaparin. ASA and ticlopidine with that of
      antiplatelet therapy alone after coronary stent placement in patients at
      increased risk of stent thrombosis. Target enrolment of 2000 patients began in
      December 1996 and is expected to be complete by the end of 1998. In summary, the
      ENTICES pilot study demonstrated that the low molecular weight heparin enoxaparin
      is safe and effective for use with ASA and ticlopidine for elective stent
      patients. The ATLAST trial should provide results on whether enoxaparin is
      beneficial in patients at high risk for stent thrombosis.

PMID- 9779033
TI  - [Pneumococcal infection and its vaccine prophylaxis].

PMID- 9779034
TI  - [Epidemiology of pneumococcal infections in Europe].

PMID- 9779035
TI  - [Epidemiology of systemic Streptococcus pneumoniae infections].
AB  - OBJECTIVES: Invasive pneumococcal infections (bactereimia and meningitis) and
      pneumonia raise an authentic public health problem. We examined the epidemiology
      of these three different diseases. METHODS: For bacteremia and meningitis, data
      were collected from the National Public Health network in France. Incidence of
      pneumonia was calculated by applying ratios published in the literature to three
      different types of incidence data (bacteremia, pneumonia hospitalizations in
      Haute-Savoie and community acquired pneumonia in general practices). RESULTS:
      Annual incidence of meningitis was almost 1 per 100,000 inhabitants and 86 per
      100,000 for bacteremia. Incidence was highest infants (< 5 years) and the elderly
      (> 65 years). All three of the calculation methods gave a convergent estimation
      of pneumonia cases with an average 132,000 cases per year, i.e., 220 per 100,000
      inhibitants. This incidence was higher above 60 years of age. Death rate was
      unknown. Only 2.8% of the death certificates mentioned pneumonia. This give
      between 5,900 and 15,484 deaths, including 95% after the age of 60. CONCLUSION:
      Pneumococcal infections remain an authentic public health problem, both in terms
      of morbidity and mortality.

PMID- 9779036
TI  - [Clinical aspects of pneumococcal pneumonia].

PMID- 9779037
TI  - [Streptococcus pneumoniae: serotypes, invasive and antibiotic resistant strains.
      Current situation in France].
AB  - OBJECTIVES: Anti-pneumococcal antibiotic therapy has reduced morbidity and
      mortality of pneumococcal infections, but this success has retarded wide
      application of vaccination. The emergence and worldwide diffusion of antibiotic
      resistant strains raises an important public health problem. The current
      situation requires determining the respective roles of antibiotic therapy and
      vaccine immunoprophylaxy. The aim of this work was to examine the data collected
      by the French National Pneumococci Registry. METHODS: The Nation Surveillance
      Network for Pneumococcal Infections was initiated in France in 1984. With this
      registry, it has been possible to follow regularly the evolution of serotypes and
      their sensitivity to antibiotics in 34,130 strains received from 1984 to 1996 and
      to compare these results with the clinical data. RESULTS: Serotyping the invasive
      strains has shown that the relative frequency of these serotypes has been stable:
      the 23-valence pneumococca vaccine provided good serotype coverage from 1984 to
      1996 (87.2% of the invasive strains isolated in 1996 belonged to the vaccine
      types). Penicillin-resistant pneumococci comprised 3.8% of the strains, isolated
      in 1987 and 42.8% of those isolated in 1996. Two-thirds of these penicillin
      resistant pneumococci had high-level resistance and an equivalent percentage were
      multiresistant. The consequences of resistant strains on antibiotic therapy for
      pneumonia, acute otitis and meningitis is discussed. CONCLUSION: Bacterio
      clinical surveillance networks provide regular epidemiological data aimed at
      better use of antibiotics and the promotion of vaccination campaigns. In the
      future, the vaccination of children under 2 years of age with new conjugated
      polysaccharide vaccines should be an essential step in the global strategy
      against pneumococcal infections. The vaccinal formula of such a pediatric vaccine
      would contain 10 valences, defined according to the serotype results we have
      obtained: 1, 3, 4, 6, 7, 9, 14, 18, 19, 13. This vaccine would cover 86.1% of the
      invasive strains and 90.7% of the strains isolated from children with acute
      otitismedia.

PMID- 9779038
TI  - [Efficacy of pneumococcal vaccination].
AB  - POLYVALENT VACCINE: Pneumococcal vaccination is based on the antigenic properties
      of polysides carried on the bacterial capsule which induce production of
      bactericidal serotype-specific antibodies. The 23 serotypes contained in the
      current vaccine cover 85 to 90% of all strains observed in pneumococcal
      infections in Europe. PROVEN EFFICACY: Prospective and retrospective studies have
      demonstrated that pneumococcal vaccination can prevent 60 to 80% of invasive
      pneumococcal infections in immunocompetent elderly subjects and/or persons in
      high-risk groups with underlying disorders. TARGET POPULATION: Immunocompetent
      persons in the 60-65 year and older age group comprise the target population for
      pneumococcal vaccination. Incidence and mortality of pneumococcal infections is
      high in this group. Simple vaccination strategies should be implemented.

PMID- 9779039
TI  - [Economic evaluations of pneumococcal vaccination. A critical analysis].

PMID- 9779040
TI  - [Pneumococcal infection and anti-pneumococcal vaccination programs in Canada].

PMID- 9779041
TI  - [Introduction and implementation of pneumococcal vaccination in Belgium].

PMID- 9779042
TI  - [Pneumococcal vaccine in Great Britain].

PMID- 9779043
TI  - [Expansion of pneumococcal vaccination in industrialized countries: will France
      join the movement?].

PMID- 9779044
TI  - [Anti-pneumococcal vaccination in France: future trends].

PMID- 9779045
TI  - [Efficacy and good tolerance of cotrimoxazole as treatment of cerebral
      toxoplasmosis in AIDS].
AB  - OBJECTIVE: Non-viral opportunistic infections involving the central nervous
      system in AIDS patients most commonly result from toxoplasmic encephalitis (TE).
      Combination pyremethamin (pyr)/sulfadiazine (sulf) is the mainstay treatment for
      TE, but many patients experience severe adverse events occasionally requiring
      discontinuation of this antitoxoplasmic medication. This investigation assessed
      the effects of an open, prospective trial of alternative
      trimethroprim/sulfamethoxazole: cotrimoxazole (CTX) therapy for TE in AIDS
      patients. PATIENTS AND METHODS: The subjects were 18 AIDS patients with a first
      presumptive attack of TE (Group 1) and 9 relapsing patients, including 6 out of
      Group 1 (Group 2). We gave CTX as a therapy at the dose of 960 mg four times a
      day for 48 hours, then 960 mg three times a day for two weeks, followed by 960 mg
      twice daily until computed tomography showed complete disappearance of active TE
      lesions. Life-long maintenance therapy consisted to CTX 960 mg daily. RESULTS:
      Group 1: Seventeen patients improved clinically and achieved complete resolution
      on computed tomography scars over a mean period of 33 days (range: 21-56). Only
      one patient was withdrawn from the study at day 18 due to a severe skin rash.
      Neither serious hematologic nor liver toxicity were observed. Under maintenance
      therapy, 7 patients relapsed after an average duration of 15.5 months. Relapses
      were precipitated either by poor compliance (5/7) or erronenous CTX protocol
      (2/7). Group 2: There were 15 relapses affecting 9 patients who were treated
      successfully with CTX. CTX was discontinued in one relapsing patient who
      experienced a Stevens-Johnson syndrome on day 13. This patient had previously
      experienced cutaneous intolerance to sulfadiazine. CONCLUSION: A relative low
      dose regimen of CTX appears to be strongly efficient and safe treatment for
      toxoplasmic encephalitis in AIDS. Such a study is of particular interest for
      developing countries where TE is highly prevalent, given the wide availability of
      CTX which could be proposed as an economic first line therapy.

PMID- 9779046
TI  - [Cutaneous vasculitis after hepatitis B vaccination with recombinant vaccine in a
      renal transplant patient].
AB  - BACKGROUND: Cutaneous vasculitis is a known complication of hepatitis B
      vaccination with recombinant vaccine. CASE REPORT: A renal transplant recipient
      with the HLD-DR4 susceptibility antigen developed histologically proven cutaneous
      vasculitis with serum antibodies after vaccination with anti-hepatitis B
      recombinant vaccine. The skin manifestation, evolved favorably after
      discontinuation of the immunization and bed rest. DISCUSSION: This case suggests
      that anti-hepatitis B vaccination with recombinant vaccine can produce cutaneous
      vasculitis in renal transplant recipients. The vaccination strategy in this
      population should be revisited.

PMID- 9779047
TI  - [Polyarthralgia disclosing hyperthyroidism. Two case reports].
AB  - BACKGROUND: We report two cases of rheumatism associated with hyperthyroidism. In
      both cases, arthralgia totally regressed after thyroid treatment. CASE REPORTS:
      Two 79-year-old and 59-year-old women developed manifestations of polymyalgia
      rheumatica and psoriasis arthritis respectively. Corticosteroid therapy was
      ineffective and followed by manifestations of hyperthyroidism. The first patient
      was treated with carbimazole and the second with thyroidectomy. Once the
      hyperthyroidism was controlled, both patients experienced a dramatically rapid
      cure of their arthralgias. DISCUSSION: Scalpulo-humeral periarthritis is the main
      articular complication of hyperthyroidism. True manifestations of "thyrotoxicosis
      rheumatism" are unusual and may be linked with a direct toxicity of the thyroid
      hormones on joint cartilage or with an autoimmune manifestation of
      hyperthyroidism.

PMID- 9779048
TI  - [Japanese encephalitis: an exceptional imported arbovirus].

PMID- 9779049
TI  - [Toxic risks in new pets. Seven cases of poisoning by exotic animals collected in
      1997 at the Marseilles Antipoison Center].

PMID- 9779050
TI  - [Chronic obstructive lung disease complicated by Pasteurella multocida
      bronchitis].

PMID- 9779051
TI  - [Primary pulmonary arterial hypertension associated with primary biliary
      cirrhosis].

PMID- 9779052
TI  - [Therapeutic evolution: towards a cloning of prescriptions].

PMID- 9779053
TI  - [Treatment of breast cancer].
AB  - EPIDEMIOLOGY IN FRANCE: Breast cancer causes 11,000 deaths annually in France and
      25,000 new cases are diagnosed each year. Currently, the overall survival rate is
      73% at 5 years and 59% at 10 years. Treatment and outcome depend largely on stage
      at diagnosis and metastatic extension, but many questions remain open. NON
      METASTATIC BREAST CANCER: Breast conserving tumorectomy with nodal dissection and
      radiation therapy is the rule for small tumors measuring less than 3 cm, although
      there is still some debate on safety margins and the appropriate attitude in case
      of invasion. Likewise, there are arguments both for and against primary
      chemotherapy before tumorectomy. Currently, primary chemotherapy should be given
      in all cases of inflammatory cancers and preferentially for large tumors. Nodal
      dissection is essentially a diagnostic procedure and is almost always performed
      although trials evaluating the value of the sentinel node may have an effect on
      current attitudes. Despite recent advances in adjuvant therapy, dose and
      combination of chemotherapy are still open questions. There is however a
      consensus that chemotherapy should be prescribed for all premenopausal patients
      with node negative and adverse prognosticators and for all patients under 70 with
      nodal invasion associated with hormonotherapy after menopause if hormone
      receptors are positive. METASTATIC BREAST CANCER: At this stage, remission
      together with quality of life are the primary treatment goals. The best response
      rates (around 65%) are obtained with polychemotherapy protocols including
      anthracyclins and complete remission can be obtained in approximately 15% of the
      patients. There is some hope that chemoresistance may be curtailed with new
      agents such as vinorelbin or the taxane family. High-dose chemotherapy with
      hematopoietic rescue is another avenue of research aimed at reducing
      chemoresistance and improving survival. Overall response to hormone therapy is
      around 30%. Response rate peaks near 70% in cases positive for estrogen and
      progesterone receptors, but falls to only 10% if hormone receptors are absent.
      The role of new hormone therapies using new antiestrogen and antiaromatic
      compounds remains to be determined. AN ONGOING CHALLENGE: Mortality due to breast
      cancer has started to decline in developed countries despite increasing
      incidence. This reduction is undoubtedly related to advances in hormone therapy
      and adjuvant chemotherapy but also to screening programs and early diagnosis. In
      the Scandinavian countries, it has been demonstrated that mortality can be
      reduced to the order of 30 to 40% with mass screening, a challenge which should
      be met in France.

PMID- 9779054
TI  - [Non-Hodgkin malignant lymphoma].

PMID- 9779055
TI  - [Role of calcium and magnesium in the secretion and the synthesis of parathyroid
      hormone at the cellular level].

PMID- 9779056
TI  - [Role of phosphate, vitamin D and acidosis in the secretion and synthesis of
      parathyroid hormone at the cellular level].

PMID- 9779057
TI  - [Physiopathology of parathyroid hyperplasia].

PMID- 9779058
TI  - [Empirical antibiotic therapy for nosocomial pneumonia acquired in assisted
      ventilation].

PMID- 9779059
TI  - [Guidelines for third-party-financed research plans. The provisional final
      version of 20 March 1998].

PMID- 9779060
TI  - [The impact factor: a critical analysis].
AB  - The impact factor, provided by the Institute for Scientific Information,
      Philadelphia (PA), has become the most important evaluation tool for scientific
      research and academic work. It is calculated by dividing the number of current
      year citations to the source items published in the journal during the previous
      two years. In market research, the impact factor provides quantitative evidence
      for editors and publishers for positioning their journals in relation to the
      competition. Despite its popularity, the parameter should be used with careful
      attention to the many phenomena that influence citation rates. The correlation
      between the citation frequency of a certain article and the impact factor of the
      journal in which it is published is questionable. A few articles have many
      citations and the rest are sparsely cited or not at all. Citation impact is more
      a measure of utility than of scientific value. Authors' selection of references
      is subject to biases unrelated to quality. Moreover, there is a tremendous bias
      towards English language journals compared with those in other languages.
      Finally, different specialties exhibit different ranges of peak impact. The
      impact factor favours research areas that promote many short-term studies.
      Conversely, a tendency to treat clinical investigations as less important is
      created.

PMID- 9779061
TI  - [Local fibrinolysis of peripheral arterial occlusions].
AB  - PURPOSE: Since their discovery more than 60 years ago fibrinolytic agents have
      shown their therapeutical efficiency in myocardial infarction and other
      thromboembolic disorders in clinical studies. Local catheter fibrinolysis as an
      alternative to surgical embolectomy was established in the mid eighties. Fibrin
      specific agents such as rt-PA and pulse-spray fibrinolysis as a new catheter
      technology were developed in order to improve the efficiency of local
      fibrinolysis and to minimize complications such as bleeding. The purpose of this
      paper is to review the historical and recent developments of fibrinolytic agents
      and catheter technologies, and to describe the methods, indications, and
      complications of local fibrinolysis.

PMID- 9779062
TI  - [The demonstration of blood flow in focal breast lesions by power-Doppler
      sonography. A new approach to assessment?].
AB  - PURPOSE: Power-Doppler sonography is regarded as a very sensitive method for
      detecting low-velocity and low-volume blood flows. The purpose of our study was
      to investigate whether increased vascularity in breast carcinoma can be
      visualized by power-Doppler sonography and whether new criteria for
      differentiating benign and malign lesions can be found. METHOD: 315 patients were
      examined with a 13-MHz high-resolution linear transducer. If a suspicious lesion
      was found, it was evaluated further by power-Doppler sonography. Compared to
      normal breast parenchyma (reference structure), a focal increase in blood flow
      signals was registered using a 3-step grading system with a 4th step for no flow
      increase. RESULTS: In 97 cases the sonographic findings were correlated with
      histology (n = 95) or cytology (n = 2). There were 50 benign lesions, 42 cases of
      invasive and 5 cases of in-situ carcinoma. 73.5% benign lesions showed no or just
      minimal increases in flow signal. 81% of invasive cancer presented middle- or
      high-flow increases compared to normal breast parenchyma. The extend of flow
      increase was linked to tumor size in invasive cancer. In stage T1b to T4, 94.3%
      of invasive carcinoma presented middle or high flow increases. CONCLUSION: Power
      Doppler sonography is able to visualize vascularization in breast tumors.
      According to first clinical results PD sonography is a promising additional
      diagnostic tool which seems to offer new criteria for differential diagnosis in
      breast tumors.

PMID- 9779063
TI  - [Automated mammary sonography and mammography: the differentiation of benign and
      malignant breast lesions].
AB  - PURPOSE: A prospective study on the differentiation of breast lesions was carried
      out using experimental combination schemes of mammography and automatic
      sonography. MATERIALS AND METHODS: X-ray mammograms and a B image from automatic
      sonography of 39 malignant and 41 benign lesions as well as 40 cases without
      lesions were separately examined by four experienced diagnosticians. The
      observers differentiated the findings mammographically and by measurement in the
      B images. RESULTS: For two examiners the combination of mammography and automatic
      sonography gave with regard to the differentiation of breast lesions an
      improvement in sensitivity of 3 or 5% and in specificity of 31 and 18%,
      respectively, as compared to mammography alone while for the other two examiners
      an improved specificity of 21 and 36%, respectively, was accompanied by an 8 and
      10% decrease in sensitivity as compared to mammography alone. CONCLUSIONS: The
      differentiating criteria from automatic sonography and mammography can, in
      principle, be used to evaluate the dignity of breast lesions. However, an
      optimization is necessary since the improvement in specificity does not
      compensate the loss in sensitivity.

PMID- 9779064
TI  - [The significance of magnetic resonance venography in the pre-interventional
      clarification of a malignant superior venous obstruction].
AB  - PURPOSE: Comparison between peripheral digital subtraction venography (DSV) and
      magnetic resonance venography (MRV) in planning for stent placement in malignant
      superior central venous obstruction. METHOD: 19 patients with malignant central
      vein obstruction were examined by DSV (n = 19) and MRV (n = 19). For each patient
      12 segment-vessel evaluation was performed to review for obstruction and then
      compared with the gold standard--selective catheter phlebography--performed at
      the time of stent insertion. Additionally, tumor extension and collateral venous
      outflow was noted. RESULTS: Sensitivity, specificity, and accuracy amounted to
      92%, 96%, and 95% for DSV and 98%, 100%, and 100%, respectively for MRV. The
      McNemar test revealed a significance between MR venography and DSV. CONCLUSIONS:
      With regard to planning of stent placement, a more exact evaluation was possible
      with MR venography than with DSV. Thus, MR venography can replace DSV as the
      method of choice for clarifying malignant superior central vein obstructions
      prior to stent placement.

PMID- 9779065
TI  - [Transmyocardial laser revascularization--the initial experiences of imaging in
      MRT].
AB  - PURPOSE: Imaging of myocardial signal alteration and perfusion differences after
      transmyocardial laser revascularization (TMLR). METHODS AND MATERIAL: 5 patients
      suffering from coronary vessel disease underwent MRI (0.5 T) pre- and 4-7 d post
      TMLR. T1-weighted spin echo sequences were acquired ECG-triggered native and
      after injection of gadolinium. Qualitative analysis was performed on both native
      and contrast-enhanced images. Myocardial signal alterations and wall changes were
      evaluated. Qualitative and quantitative analyses of contrast-enhanced images were
      performed with regard of post-therapeutic perfusion differences. Analysis was
      based on contrast-to-noise (C/N) data obtained from operator defined "regions of
      interest". RESULTS: Visualization of laser-induced channels was not possible.
      Native scans obtained before and after TMLR revealed no significant change with
      regard to the qualitative analysis. Both qualitative and quantitative analyses
      demonstrated a posttherapeutic increase of C/N in both the left ventricular
      myocardium (64.4 pre-TMLR; 89.1 post-TMLR; p = 0.06) and the septum in the
      majority of cases. No significant difference between laser-treated left
      myocardium and untreated septum was observed (p > 0.05). DISCUSSION: Single
      myocardial laser channels could not be visualized with a 0.5-T MRI. However,
      visualization of increased myocardial contrast enhancement in laser-treated left
      ventricular myocardium was evident in the majority of cases on the basis of
      qualitative and quantitative analyses. CONCLUSIONS: The MRI technique used
      enabled a first, limited depiction of TMLR-induced myocardial changes. The
      clinical value and impact still have to be defined.

PMID- 9779066
TI  - [Idiopathic pulmonary ossification].
AB  - OBJECTIVE: Linear and round shadows are very often revealed on chest radiographs.
      A rare entity most commonly appearing as branching linear shadows of calcific
      density involving a limited area of the lung is the so-called disseminated
      pulmonary ossification (DPO). Only 141 cases have been reported worldwide up to
      now since the first description. MATERIAL AND METHODS: A study on 490 autopsies
      was performed to find out the frequency of DPO. In case of DPO we compared the
      structures with the chest radiographs and CT of the patients. Further, we
      evaluate clinical communities of patients with DPO. RESULTS: From a total of 490
      lungs eight were identified with DPO (1.6%). The mean age of patients with DPO
      was 80.2 years, the male/female ratio seven to one (mean age of all patients:
      64.6 years, male/female ratio one to one). All cases were associated with
      hypertension followed by extreme arteriosclerosis. In 5 cases there was a proven
      extrapulmonary carcinoma and a renal insufficiency. In 4 cases we found diabetes
      mellitus. At postmortem radiographs and CT, a collection of small rounded
      calcific nodules and further linear shadows arranged in a branching or net-like
      configuration was identified. This was compared with the chest radiographs of the
      patients. There were no dysfunctions of lungs due to DPO. CONCLUSIONS: In chest
      radiographs of elderly men the differential diagnosis "DPO" should be given more
      importance.

PMID- 9779067
TI  - [The value of sonography in the intensive care unit for the diagnosis of
      diaphragmatic paralysis].
AB  - PURPOSE: To assess the value of bedside sonography in the detection of
      diaphragmatic paralysis in patients in the intensive care unit. METHODS: In this
      study, 100 patients who were admitted to the intensive care unit after thoracic
      operations were evaluated. Sonography of each hemidiaphragm was performed with
      coronal scans at the mid-axillary line on both sides with the patient supine.
      Absent and paradoxical diaphragmatic movement was considered to be indicative of
      diaphragmatic paralysis. All patients underwent additional fluoroscopy within 5
      days. RESULTS: In 13 patients (13%) sonography revealed diaphragmatic paralysis.
      All these results were confirmed with fluoroscopy resulting in a sensitivity and
      specificity for sonography of 100%. CONCLUSION: Bedside sonography of the
      diaphragm at the intensive care unit is a reliable tool for diagnosing
      diaphragmatic paralysis.

PMID- 9779068
TI  - [Ultrafast contrast-enhanced 3D MR angiography in the preoperative diagnosis of
      liver tumors].
AB  - PURPOSE: To evaluate the accuracy of 3D-MRA in preoperative staging in
      correlation to intraoperative and histological results. METHODS: In 30 patients
      with focal liver lesions axial and coronal MR sequences (T1w-Flash 2D, T2w-TSE
      unenhanced. T1w-Flash 2D, TRUE FISP contrast-enhanced) as well as coronal breath
      hold MRA were performed. The technical parameters of the MRA were as follows;
      TR/TE 5/2 ms, flip angle 40 degrees, 32-40 partitions with an effective slice
      thickness of 2-3 mm, acquisition time 26 s, matrix 128 x 256, FOV 320 x 320 to
      400 x 400. RESULTS: In 23/30 patients liver resection was performed. Correct
      prediction of segmental localization was achieved in preoperative MRI of 22
      patients (98%). The presumed histology was correct in 20/23 cases (87%). The
      evaluation of the hepatic vascular structures was correctly predicted in all
      cases. By use of multiplanar reconstructions and single image view of the 3D data
      base of MRA, additional information could be obtained in 13 patients.
      CONCLUSIONS: Breath-hold 3D-MRA gives certain information on localization and
      relation of vascular structures to focal hepatic lesions. In presentation of
      portal venous structures MRA is superior to conventional angiography.

PMID- 9779069
TI  - [The diagnosis and imaging of the a. hepatica after orthoptic liver
      transplantation--a comparison of frequency-modulated and amplitude-modulated
      color Doppler sonography].
AB  - PURPOSE: We examined whether amplitude-modulated color Doppler (power Doppler)
      sonography provides a better anatomic imaging of the vascular course of the
      hepatic artery after liver transplantation. PATIENTS AND METHODS: 82 patients
      were examined with Doppler sonography after liver transplantation. The distal
      section of the hepatic artery was imaged both with frequency-modulated color
      Doppler (color Doppler) and power Doppler and a Doppler spectrum derived from
      each mode for determination of the flow velocity. RESULTS: Native imaging of the
      hepatic artery was possible in 78/82 patients, in 2/82 patients only after
      administration of Levovist, and in 2/82 patients it could not be seen. In these
      two patients the diagnosis of hepatic artery occlusion was confirmed by
      angiography. The anatomic course was demonstrated more longitudinally by power
      Doppler than by color Doppler (p < 0.001; chi 2 test) which made the angle
      correction easier. A disadvantage of power Doppler was the lack of image contrast
      to the portal veins; thus evaluation of the vascular course in this section was
      better possible with color Doppler by means of a specifically generated aliasing
      in the flow of the hepatic artery (p < 0.001; chi 2 test). Determination of the
      flow velocity showed no significant differences between color and power Doppler
      supported duplex sonography. CONCLUSIONS: The combined use of color Doppler and
      power Doppler improves visualization of the hepatic artery after liver
      transplantation. The lack of visualization of the vessel after administration of
      Levovist is diagnostic for occlusion of the vessel.

PMID- 9779070
TI  - [The MRT and MRA of kidney transplants--vascular and perfusion assessment].
AB  - PURPOSE: To document the value of fast contrast enhanced-sequences in the
      assessment of the vascular supply and parenchymal perfusion in renal transplants.
      PATIENTS: 18 recipients of a renal transplant were examined with a 1.5-tesla-MR
      system. The protocol included fast contrast enhanced 3D MR angiography and
      coronal 2D GRE sequences. The transplant artery and vein were assessed as well as
      regional parenchymal perfusion. RESULTS: 3D MRA detected three transplant artery
      stenoses and one occlusion. In addition, two renal vein thromboses and one
      compression were identified. Perfusion deficits were documented in 8 renal
      transplants: renal infarction (n = 4), cortical necrosis (n = 2), acute tubular
      necrosis (n = 1) and venous ischemia (n = 1). Fluid collections were documented
      as well as dilation of the collecting system and abnormalities of the surrounding
      tissues. CONCLUSION: Contrast enhanced MRI and MRA permit a comprehensive
      assessment of renal transplants without inducing nephrotoxicity.

PMID- 9779071
TI  - [The percutaneous transarterial embolization therapy of traumatic kidney
      hemorrhages].
AB  - PURPOSE: To demonstrate the possibility of transarterial, superselective
      embolization after traumatic kidney injury and hemorrhage in patients usually
      treated by surgery. METHODS: In a series of 16 patients aged 21 to 86 years (mean
      37 years) external trauma led to kidney damage and consecutive bleeding. After
      diagnostic angiography (5 F) the exact site of hemorrhage was detected and
      treated by superselective embolization via a coaxial catheter system (2.7 F)
      either by coils (n = 5) or liquid agents (ethibloc, n = 11). RESULTS: In all
      patients bleeding was stopped interventionally. Additional surgical treatment was
      not necessary in any case. In one older patient with preinterventionally known
      reduced kidney function, the excretion function decreased to creatinine levels of
      about 3.6 mg/dl after therapy and led to compensated nephric insufficiency. Other
      complications were not observed. CONCLUSION: Interventional embolization is a
      well-tolerated and effective treatment modality after traumatic kidney
      hemorrhage. After exclusion of other injuries obligate for surgery, percutaneous
      transarterial therapy may help to avoid an operation. This reduces the risk of
      narcosis and treatment especially in multimorbid patients.

PMID- 9779072
TI  - [The value of a fabric-coated self-expanding stent in iliac arterial occlusions
      or aneurysms--the primary and long-term results].
AB  - PURPOSE: The objective of this study was to analyze the primary and long-term
      results of implanting self-expanding covered nitinol stents (EndoPro I) in iliac
      arteries. MATERIAL AND METHODS: A total of 48 EndoPro (length 8.3 +/- 4.2 cm)
      were implanted in 39 patients. In 22 cases (group A) the implantation was
      performed after excimer laser-assisted recanalization (PTLA) of long iliac
      occlusions (mean 9.8 +/- 3.9 cm). Other indications were aneurysmatic lesions (n
      = 16) and one arterial perforation (group B). RESULTS: In 21 of 22 patients of
      group A the patency of the blood vessel was successfully restored. In all cases
      of group B the aneurysmatic lesions were finally excluded. This was correlated
      with a clinical improvement of at least one grade (Rutherford criteria) in 86.4%
      of patients (group A). The primary patency rate based on clinical examination
      (treadmill test) and color-coded Doppler was evaluated at 6 (89.7%), 12 (87.1%),
      and 24 (84.2%) months follows up, respectively. Subacute thromboses occurred in
      two, relevant restenoses in three cases (group A). In three of these 5 cases the
      vessel segment was successfully reopened by PTLA or rt-PA thrombolysis, leading
      to secondary patency rates of 94.9% at 6 and 92.1% at 12 and 24 months,
      respectively. CONCLUSION: In cases of relevant dissection following PTLA of long
      pelvic artery occlusions implantation of covered stents is effective to stabilize
      the results. Furthermore, the device is well applicable to seal arterial ruptures
      or aneurysms.

PMID- 9779074
TI  - [Bronchobiliary fistula as a complication of Bulau drainage].

PMID- 9779073
TI  - [Positron-emission tomography of the skeletal system using 18FNa: the incidence,
      pattern of the findings and distribution of benign changes].
AB  - PURPOSE: We evaluated the frequency, distribution and appearance of benign
      lesions in 18F-PET scans. METHODS: Between March 1996 and May 1997, 18F-PET scans
      were performed in 59 patients in addition to conventional planar bone
      scintigraphy. Eleven patients were subjected to additional SPECT imaging. The
      main indication was searching for bone metastases (58 pat.). The diagnosis was
      confirmed radiologically. RESULTS: With 18F-PET in 39 patients (66.1%) 152 benign
      lesions, mostly located in the spine were detected. 99mTc bone scans revealed 45
      lesions in 10 patients. Osteoarthritis of the intervertebral articulations (69%)
      or of the acromioclavicular joint (15%) were the most common reasons for
      degenerative lesions detected with 18F-PET. Osteophytes appeared as hot lesions
      located at two adjacent vertebral endplates. Osteoarthritis of the intervertebral
      articulations showed an enhanced tracer uptake at these localizations, whereas
      endplate fractures of the vertebral bodies appeared very typical; solitary
      fractures of the ribs could not be differentiated from metastases. Rare benign
      lesions were not studied. CONCLUSION: Most of the degenerative lesions (84%)
      detected with 18F-PET had a very typical appearance and could be detected with
      the improved spatial resolution and advantages of a tomographic technique. 18F
      PET had an increased accuracy in detecting degenerative bone lesions.

PMID- 9779075
TI  - [Recurrent spontaneous pneumothorax as the earliest indication of the pulmonary
      metastasis of a synovial sarcoma?].

PMID- 9779076
TI  - [Intra-abdominal desmoplastic small-cell tumor--the rare differential diagnosis
      of a malignant peritoneal tumor].

PMID- 9779077
TI  - [A coated stent as alternative therapy for stopping a tumor-induced arrosive
      hemorrhage].

PMID- 9779078
TI  - New direct restorative materials. FDI Commission Project.
AB  - People worldwide have become increasingly aware of the potential adverse effects
      on the environment, of pollution control and of toxic effects of food, drugs and
      biomaterials. Amalgam and its potential toxic side effects (still scientifically
      unproven) continue to be discussed with increasing controversy by the media in
      some countries. Consequently, new direct restorative materials are now being
      explored by dentists, materials scientists and patients who are searching for the
      so-called 'amalgam substitute' or 'amalgam alternative'. From a critical point of
      view some of the new direct restorative materials are good with respect to
      aesthetics, but all material characteristics must be considered, such as
      mechanical properties, biological effects, and longterm clinical behaviour.

PMID- 9779079
TI  - Response to nitrous-oxide and oxygen among dental phobic patients.
AB  - The present study evaluated the records of 27 patients (20 men, 7 women) who were
      treated under nitrous-oxide (N2O) and oxygen sedation due to extremely high
      dental anxiety. Corah's DAS and Kleinknecht's dental fear survey were completed
      by the patients. Patients who responded positively to the gas were categorised as
      N2O+ patients, whereas those who responded negatively were categorised as N2O-
      patients. A mean DAS score of 19.3 +/- 1.6 was observed for the entire
      population. No significant difference was found between N2O+ patients and N2O-
      patients in any DAS item, nor in the total scores (19.4 +/- 1.35 and 18.67 +/-
      2.24 respectively). Only in answer to the question, 'Has fear of dental work ever
      caused you to cancel or not appear for an appointment?' were the scores of N2O-
      patients significantly higher than of N2O+ patients. No differences were found
      between patients who reported pain as the source for their dental anxiety and
      those who did not; between patients with gag reflex and those without, between
      patients who had never had any dental treatment and those who had, and between
      patients who required two or three appointments before administration of the gas
      with respect to successful treatment under N2O and oxygen sedation. Among the N2O
      group, significantly more patients did not attend for two appointments or more.
      The results suggest that lack of keeping previous dental appointments may
      indicate patients' possible negative response to nitrous-oxide and oxygen
      sedation.

PMID- 9779080
TI  - Knowledge and opinions about dental human health resources planning in Mexico.
AB  - Dental human health resource planning (DHHRP), or manpower planning in Mexico has
      been plagued by fundamental contradictions. In spite of having trained a great
      many dentists in the past two decades, the dental health status of the population
      has not significantly improved. Concurrently, the relative scarcity of patients
      in relation to the number of practising dentists seems to be more marked, a
      critical issue since most dental care is delivered under private schemes. In the
      present investigation, 196 practising dentists in Mexico City were interviewed to
      establish their knowledge and opinions about DHHRP, and their views about the
      introduction of innovative alternatives in transforming, evaluating and planning
      human health resources. Concerns were: a need to examine and re-define the aims,
      skill content and marketability of professional training in professional
      practice; a lack of consensus as to how this is to be achieved; and a degree of
      awareness that professional practice has a limited scope in meeting the challenge
      of providing adequate care because of maldistribution of dentists and of limited
      financial resources of patients.

PMID- 9779081
TI  - Cariostatic effects of a xylitol/NaF dentifrice in vivo.
AB  - Xylitol has been shown to reduce plaque acids, but its topical cariostatic effect
      has been equivocal. The purpose of the studies reported here was to optimise the
      xylitol/NaF combination in dentifrices for an improved anticaries activity. In
      the first study, the combination of 10 per cent xylitol with 1100 ppm F (NaF),
      1100 ppm F (NaF), and placebo dentifrices were tested in a rat caries model to
      assess the cariostatic effect. The combination was significantly more effective
      than fluoride by itself (P = 0.05). The xylitol/NaF combination provided
      significantly more remineralisation of dentine than fluoride by itself.
      Collectively, results of these investigations confirm the improved anticaries
      effectiveness of the xylitol/NaF combination in a variety of animal and intra
      oral models. A three-year clinical study confirmed these findings.

PMID- 9779082
TI  - Gigantiform Torus palatinus: review of the literature and report of a case.
AB  - Torus Palatinus is a common, benign, anomaly in Caucasian populations. Rarely, in
      dentate patients, does it produce problems which justify removal. Such a case is
      described, including a literature review, surgical management and discussion of
      the entity.

PMID- 9779083
TI  - The association of urbanisation with the prevalence of dental caries among
      schoolchildren in Nigeria new capital territory.
AB  - The aim of this study was to examine the association of urbanisation and social
      class with dental caries. A multi-stage stratified cluster sampling technique was
      used to select schoolchildren (n = 915). Clinical examination was carried out in
      daylight according to WHO criteria. The distribution of the subjects between
      strata was: 315 (urban); 303 (semi-urban) and 297 (rural). The mean age of
      subjects in each strata was 11.4 years. The mean number of decayed teeth (DT) in
      the respective strata were 27 per cent; 24 per cent; and 12 per cent. Urban
      children and semi-urban had higher risk for caries than their rural reference
      group. Urbanisation had no significant effect on the caries prevalence when
      social class was controlled except among subjects from the low social class in
      semi-urban areas. The development of satellite towns around big cities do have
      implications for planning oral health services.

PMID- 9779084
TI  - Periodontal health and the role of the dental hygienist.
AB  - This study was conducted to evaluate the influence of hygienist services in an
      Israeli kibbutz (communal settlement) upon periodontal disease levels and
      periodontal treatment needs. The Periodontal Index (PI) and the Community
      Periodontal Index of Treatment Needs (CPITN) were utilised to examine 412
      subjects of which 202 adult participants resided in a kibbutz employing a
      hygienist and 210 participants resided in one of three kibbutzim lacking a
      history of hygienist employment. Examinations were conducted by two calibrated
      examiners. Results revealed a gradual increase in the CPITN and PI scores with
      age and generally statistically significantly higher periodontal pathology and
      treatment need scores among the population not employing a dental hygienist
      (especially within the 35-44 age grouping). The results of this study suggest
      that employment of a dental hygienist may be an effective approach to lower the
      burden of periodontal disease within a community.

PMID- 9779085
TI  - Analysis of epidemiological data on oral diseases in Nepal and the need for a
      national oral health survey.
AB  - This paper reviews and analyses the results of epidemiological studies on
      periodontal diseases and dental caries in Nepal and considers the need for
      additional data on oral diseases for the planning of a national oral health
      strategy. Almost all subjects aged 12 to 19 years (68-97 per cent) and 35 to 44
      years (93-100 per cent) had calculus. The various studies showed that a median 29
      per cent of subjects aged 35-44 years had deep periodontal pockets. According to
      this estimate it can tentatively be concluded that Nepal belongs to the 15 per
      cent of countries in the world where periodontal conditions of the population are
      among the worst. An accurate DMFT-value for different age groups at present
      cannot be estimated due to period and sampling effects. The observed cohort
      effect over time suggests that caries has increased in the 12-19 years age group
      in Nepal in the period 1980-1996. The estimated range of DMFT-values for 12 years
      old children is between 0.6-1.9 and for 35 to 44 years old persons between 2.5
      4.0. With these DMFT-values Nepal belongs to the countries with a 'low to very
      low' caries experience according to the WHO decay rating. The present
      epidemiological data do not justify a claim for a national oral health survey as
      a starting point for a national plan of oral health since more accurate data do
      not add additional value to that planning, particularly not in poor countries as
      Nepal where the oral health service is still in its infancy.

PMID- 9779086
TI  - An assessment of cross-infection control procedures among English-speaking
      Caribbean general dental practitioners. A regional preliminary study.
AB  - A survey was undertaken to assess the level of compliance with recommended
      infection control procedures among English-speaking Caribbean general dental
      practitioners. A four page questionnaire was sent to all practitioners in 18
      English-speaking Caribbean islands. A response rate of 32 per cent was obtained.
      A large proportion of dentists followed the recommended barrier techniques
      particularly the use of gloves and facemasks. The most commonly available methods
      of sterilisation were steam autoclaves (82 per cent) and cold solutions (94 per
      cent). Seventy four per cent of respondents had received hepatitis B vaccination.
      A high percentage of dentists showed willingness to treat HBV (95 per cent) and
      HIV (84 per cent) carriers and this level of willingness to treat infectious
      patients has rarely been reported previously. There is an urgent need for further
      improvements to avoid getting inoculation injuries and splatters in the face or
      eyes with body fluids. Disposal of sharps and collection of solid waste are to be
      upgraded. The Caribbean Atlantic Regional Dental Association is planning to carry
      out similar research before the end of the year 2000.

PMID- 9779088
TI  - Oral lesions in a Jordanian population.
AB  - Since there is little information available on the prevalence of oral lesions in
      the Middle East population generally, and no data on the Jordanian population,
      this study was undertaken to correct this deficiency in our knowledge. During
      this investigation 2175 consecutive asymptomatic dental patients attending the
      Initial Treatment Unit in the Faculty of Dentistry, Jordan University of Science
      and Technology were examined for the presence of oral lesions. A total of 30
      different oral lesions and conditions were diagnosed. Fordyce's granules and tori
      were the most common conditions diagnosed in 49 per cent and 15.7 per cent of the
      subjects respectively. Larger scale studies are required on an unselected group
      of the Jordanian population to assess the overall significance of the findings.

PMID- 9779087
TI  - Latex exposure and allergy: a survey of general dental practitioners and dental
      students.
AB  - Gloves are now worn routinely by most general dental practitioners and dental
      students while treating patients, with latex being the most commonly used glove
      material. By means of a questionnaire, this study surveyed 160 students in one
      dental school and 300 randomly selected general dental practitioners in respect
      of their exposure to latex. Response rates were 74.4 per cent and 57.3 per cent
      for dental students and practitioners respectively. Adverse skin reactions to the
      wearing of latex gloves was reported by 18.5 per cent of dental students and 22.8
      per cent of practitioners. Analysis of the data indicated that there was an
      association between student year and adverse skin reaction to latex, an
      association between years in dental practice and adverse skin reaction to latex
      and a strong relationship between dentist's gender and adverse skin reaction to
      latex. Respondents who suffered from eczema or food allergies were more likely to
      have experienced an adverse skin reaction to latex glove wearing. It is concluded
      that adverse reactions to latex occur in significant numbers of dental students
      and dental practitioners, with those who reported personal and familial atopy
      being more likely to be affected.

PMID- 9779089
TI  - How the Middle West was won: women enter dentistry.
AB  - At the beginning of the 19th century, the settlement of the Middle West of the
      United States was taking place and soon thereafter dental schools were being
      founded. With the establishment of dental schools, dentistry slowly evolved from
      a craft transmitted by a preceptor to a profession taught within established
      schools. Starting with Lucy Beaman Hobbs Taylor, a number of women from the
      Middle West entered dental schools when they were opened to them. Many active
      women of the Middle West became dentists and provided impetus for the profession
      as well as founding of the American Association of Women Dentists.

PMID- 9779091
TI  - Identification of bacterial markers by culture technique in evaluation of
      periodontal therapy.
AB  - The aim of the present study was to evaluate whether the presence of A.
      actinomycetemcomitans, P. gingivalis and P. intermedia, as revealed by culture
      technique, could discriminate between three distinct adult patient groups, those:
      with recurrent periodontal disease, with cured periodontal disease or who were
      periodontally healthy. Forty one patients previously treated for advanced
      periodontitis were divided into recurrent or cured groups, with a third
      periodontally healthy reference group. All subjects were sampled for the three
      bacterial strains under scrutiny. Although all three micro-organisms were found
      significantly more often in diseased sites, it was concluded that a sample
      positive for all three may indicate a false record of disease activity. However,
      a sample negative for the three bacteria strongly indicates an absence of disease
      activity.

PMID- 9779090
TI  - Periodontal conditions and treatment needs, by CPITN, in the 35-44 and 65-74 year
      old population in Santiago, Chile.
AB  - A CPITN survey involving Chileans aged 35-44 and 65-74 was conducted. A random,
      stratified sample by age, gender, socio-economic status and educational level was
      obtained, comprising 1150 individuals. Prevalence of chronic inflammatory
      periodontal disease (Codes 3 + 4) was 90.89 per cent in subjects aged 35-44, and
      100 per cent in subjects aged 65-74. The total prevalence for both age cohorts
      was 92.19 per cent. Prevalence of periodontal disease was slightly lower in
      females but severity was significantly higher in males. A significant association
      between socio-economic status and periodontal health was found. Prevalence (Code
      3 + 4) was 56.44 per cent in subjects of high, 98 per cent in subjects of middle,
      and 100 per cent in subjects of low socio-economic status. Also, the mean number
      of sextants with pockets > 6 mm (1.12) and mean number of excluded sextants
      (1.43) were significantly higher in subjects of low socio-economic status. An
      association between educational level and periodontal health was apparent. The
      only subjects who were periodontally healthy were in the group with university
      education. Prevalence of CITN (Code 3 + 4) was also significantly lower in
      subjects with university education. There was also a significant association
      between educational level and loss of teeth. Concerning missing teeth, 22 per
      cent were lost due to periodontal disease and 77 per cent due to caries. The
      prevalence of periodontal disease found in this adult representative Chilean
      population indicates that the entire population needs oral hygiene instruction
      and scaling, and that 45.70 per cent need complex periodontal treatment.

PMID- 9779093
TI  - Community periodontal index and treatment needs values (CPITN) in a factory
      worker group in Cluj-Napoca, Romania.
AB  - The aim of the study was to determine the prevalence of periodontal disease and
      the treatment needs in a population of 214 factory workers in Romania. Of those
      examined, 9.34 per cent were in periodontal health (code 0), 21.49 per cent had
      gingival bleeding (code 1), 18.69 per cent had supra- or subgingival calculus
      (code 2), 32.71 per cent presented with pathological pockets 4-5 mm deep (code 3)
      and 17.76 per cent had pathological pockets 6 mm or deeper (code 4). The
      distribution of these subjects among the treatment need categories revealed that
      30.83 per cent would need improvement in personal oral hygiene (I), 51.40 per
      cent from the subjects would need treatment (I) + scaling (II) and 17.76 per cent
      would need treatment (I + II) + complex treatment (III).

PMID- 9779092
TI  - Active and inactive caries lesions in a selected elderly institutionalised French
      population.
AB  - Various epidemiological investigations have shown the high prevalence and
      incidence of caries in geriatric populations. The aim of the present study was to
      evaluate the dental status and some salivary parameters of elderly French
      subjects institutionalised in a geriatric hospital. The study population included
      117 subjects (31 males and 86 females) who were neither demented nor edentulous,
      with a mean age of 83.0 years (SD = 7.8). Crown and root caries were recorded
      according to a modified caries activity index on 17,442 surfaces (9 surfaces per
      tooth: 5 crown surfaces and 4 root surfaces). The 17,442 surfaces examined
      corresponded to 1,938 teeth. The mean number of teeth per subject was 16.6 (SD =
      7.6), more teeth remaining in the mandible than in the maxilla. The 2,985 unsound
      root surfaces showed a high percentage of active lesions (31.2 per cent) and a
      low percentage of filled root surfaces (4.5 per cent). Crowns and roots also
      presented a high percentage of destroyed surfaces: 1,446 destroyed surfaces, 8.3
      per cent of the examined surfaces. Salivary parameters (flow rate and buffer
      capacity) were also recorded. Stimulated salivary flow rate had a relationship
      with crown caries (linear regression and analysis of covariance), and buffer
      capacity with root caries (analysis of variance and covariance). The data
      illustrate critical treatment needs in French geriatric institutions. This
      situation, which appears to differ from previous reports in European and US
      elderly people, may be related to French specificities concerning oral health
      status and/or care policy, but also to the usually very old population.

PMID- 9779095
TI  - Health profile of the ageing population: the Swedish experience.
AB  - Sweden is demographically one of the oldest countries in the world. The average
      life expectancy is comparatively high. However, the total number of physical and
      mental disorders, which may affect the elderly, seems to be increasing and
      becoming more and more complicated to prevent and treat. The rapid changes in the
      human biotope, threatening the quality of life of Man, play an important role in
      this development. The elderly in the future will, thus, have a health profile
      which may differ significantly from that of today's elderly. As general health is
      largely dependent on the 'health' of the environment and oral health may be the
      mirror image of general health, dentistry has a key position and responsibility
      in the international action programme for a sustainable development (Agenda 21,
      UNCED, 1992). Therefore, traditional curricula in, for example, odontology should
      be supplemented with interdisciplinary courses with a focus on a holistic view of
      the human condition. In collaboration with UNESCO, such an educational programme
      has been developed at Goteborg University. It aims at assisting each person to
      take on an increased self-responsibility for his or her immediate environment and
      health ('individual Agenda 21'). At present, an educational network is being
      established in Eastern Europe, in collaboration with medical and odontological
      faculties at the national universities.

PMID- 9779094
TI  - Dental practice and the environment.
AB  - This paper summarises issues pertaining to the environmental effects of clinical
      practice. Using examples of environmental awareness, the concept of environmental
      auditing is introduced by way of a pointer to actions to limit the environmental
      impact of dentistry. It is concluded that environmental management and auditing
      would be advantageous to dentistry.

PMID- 9779096
TI  - Periodontal therapeutics--a viable option?
AB  - Research in recent years in periodontology has seen a shift from surgery towards
      medicine. While surgery, particularly regenerative, and including implants,
      continues to form an important element of periodontal treatment, the volume of
      treatment required and the results of recent and ongoing non-surgical studies
      clearly show that most future periodontics will be based on a physician-type
      approach. Improved diagnostics based on more precise periodontal disease
      classification, simplification of mechanical oral hygiene equipment and
      procedures, and the development of conventional and non-conventional chemical and
      physical adjuncts may be expected to reduce the rate of common periodontal
      disease advance, resulting in less complex treatments, and more of the latter
      coming to lie within the competence of the generalist and the hygienist working
      together. The rationale for non-surgical adjunctive therapy is extensive, far
      beyond the usual antimicrobial logic. It will also be important to control the
      oral microflora for systemic reasons, since increasingly strong links are being
      established between focal infection of oral origin, much of it periodontal, and a
      range of systemic diseases, including coronary heart disease, stroke,
      gastrointestinal disorders, and low birth weight, apart from severe, overt
      systemic infections. All these developments derive from a greatly improved
      understanding of the fundamentally ecological nature of the natural microbial
      biofilm that is dental plaque, and of its interactions with its human host.

PMID- 9779097
TI  - Oral health situation of schoolchildren, mothers and schoolteachers in Saudi
      Arabia.
AB  - Studies of children, mothers, and schoolteachers were carried out in the Madina
      City, Saudi Arabia. The clinical examinations of dental caries in 6 year-olds (n
      = 240) showed a mean dmft score of 6.4 and 2.9 DMFT was found among 12 year-olds
      (n = 240). Questionnaires to the mothers demonstrated poor oral hygiene habits of
      the children and the consumption of sugar was extraordinarily frequent. Annual
      visits to the dentist was reported for 45 per cent of the children and 51 per
      cent of the mothers. The level of dental knowledge of the mothers (n = 460) was
      diffuse whereas the attitudes towards prevention were positive. Self-administered
      questionnaires to teachers (n = 120) revealed positive attitudes towards school
      based oral health promotion. There is an urgent need for implementation of
      systematic oral health programmes for children in Saudi Arabia.

PMID- 9779098
TI  - Treatment injuries in dentistry--cases from one year in the Swedish Patient
      Insurance Scheme.
AB  - Eight hundred and fifty-one claims submitted to the Swedish Patient Insurance
      Scheme were studied and analysed. The most frequent claim referred to root
      fractures of roots with posts, and to root perforations also related to root
      posts. Other relatively frequent claims referred to pulpal complications in
      connection with fixed prosthodontics, root perforations related to endodontic
      treatment, and dysaesthesia. The mean latency time (the time from the actual
      treatment to the diagnosis of the injury) was for root fractures 10.6 months, and
      the mean latency time for root perforations that were not directly observed
      during preparation was 15.9 months. Pulpal complications of teeth treated with
      crowns or fixed partial dentures had a mean latency time of 7.6 months. Injuries
      with a low frequency were, for example, fracture of vital abutments for crowns or
      fixed partial dentures, damage to tissue by electrosurgery or to the floor of the
      mouth by drilling, or perforations to the antrum. Two cases of particles dropped
      into the patient's eye were also reported.

PMID- 9779099
TI  - The effect of dentine surface treatment on pulpward pressure transmission during
      crown cementation: a laboratory study.
AB  - Thirty extracted human premolars received standardised full crown preparations.
      The teeth were randomly assigned into three groups: smeared (control), etched
      (phosphoric acid gel), and bonded (Scotchbond MP). Each tooth was perfused with
      saline to establish perfusion rates at baseline for all groups, and the post
      etching stage for etched and bonded groups, post-bonding stage for bonded group,
      and post-cementation stage for all groups. Crowns made with four layers of die
      spacing were cemented with zinc phosphate cement at 100N. Pulpal pressures were
      measured with a pressure transducer. It was concluded that dentine bonding agents
      may have the potential to reduce pulpal damage caused by pressure transmission
      from cementation.

PMID- 9779100
TI  - Dental caries prevalence and treatment need in Chiriqui Province, Panama.
AB  - A pathfinder pilot survey was conducted in rural Chiriqui Province, Panama, using
      standard WHO methodology, in order to estimate dental caries prevalence and
      treatment need. Examinations for caries and treatment need were performed by six
      trained, experienced examiners. From a convenience sample of 2,597 subjects, a
      stratified cluster sample was constructed using index ages 12 and 15 years and
      age groups 35-44 and 65-74 years. The results showed a mean Decayed, Missing and
      Filled Teeth index (DMFT) of 4.08 for 12 year olds, 6.40 for 15 year olds, 13.20
      for the 35-44 age group, and 18.88 for the 65-74 age group (P < 0.001). No
      statistically significant differences by gender were found. These findings rank
      rural Panama with Mexico and Haiti when compared to the results of other Central
      American community studies. The percentage of caries free 12 year olds was 6.8
      per cent. Of the total sample, 74.7 per cent of individuals would require one or
      multiple surface restorations and 47.9 per cent would require at least one
      extraction. Restorative need was greatest in the 15 year olds. The severity of
      dental caries in this sample was moderately severe and the treatment need
      extraordinarily high.

PMID- 9779101
TI  - Dental caries and oral health behaviour situation of children, mothers and
      schoolteachers in Wuhan, People's Republic of China.
AB  - This study was undertaken in order to describe the occurrence of dental caries in
      Chinese schoolchildren and to highlight the oral health behaviour situation.
      Clinical examinations of grade 1 children (age 6, n = 381) and grade 6 children
      (age 12, n = 413) were performed. At age 6, 86 per cent of the children were
      affected by dental caries and at age 12 the mean DMFT index was 1.0. Personal
      interviews with the mothers (n = 691) showed that dental care habits of children
      were poor; 22 per cent of all children brushed their teeth twice a day and 20 per
      cent had seen the dentist within the past 12 months. Very few children (4 per
      cent) had practical support from their parents in daily toothcleaning. Self
      administered questionnaires for schoolteachers (n = 138) revealed that most (85
      per cent) are positive towards oral health education of children. Systematic
      school-based programmes should be implemented to promote oral health.

PMID- 9779102
TI  - The periodontal disease problem. A comparison between industrialised and
      developing countries.
AB  - There is no reason to believe that periodontal diseases in industrialised and
      developing countries are in principle different. That is, not in the sense that
      the problem is caused by a different set of periodontal diseases, with different
      micro-organisms and a different natural history, needing a different approach
      towards prevention and treatment. Indeed, from a public health perspective the
      relative similarities in periodontal conditions around the world are far more
      striking than the differences. The view that periodontal diseases are a much more
      prevalent and a severe problem in the developing countries seems to be true only
      in terms of poorer oral hygiene and considerably greater calculus retention,
      already at a young age, but not so clear for periodontal destruction in adults.

PMID- 9779103
TI  - Periodontal disease and tooth loss.
AB  - Numerous epidemiological studies have shown that caries is the main reason for
      tooth loss. More recent epidemiological data seem to show an increasing trend of
      tooth loss due to periodontal reasons rather than caries. In considering the
      issue of periodontal disease and tooth loss the following observations were made.
      The presence of initial attachment loss, bone height and the habit of smoking
      significantly increase the risk of tooth mortality. There is a strong correlation
      between smoking, the severity of periodontal disease and tooth mortality. Cross
      sectional population surveys of tooth loss reported lower anterior teeth to be
      the most frequently extracted due to periodontal reasons, followed by upper
      anteriors and upper second molars. However, in long term maintenance studies,
      molars were lost most frequently. Periodontal reasons for tooth loss were mainly
      mobility followed by furcation involvement. Periodontal surgery did not
      significantly enhance tooth retention in high risk groups. Ethnic differences
      observed were not significant and would need further investigations to address
      variables such as cultural differences, health habits, diet and socio-economic
      status. In conclusion, periodontal tooth mortality was found to be associated
      with the loss of periodontal attachment and risk groups with advanced
      periodontitis contributing to major tooth loss in a minority of the population.

PMID- 9779104
TI  - Dental services and needs in developing countries.
AB  - People in developing countries are burdened excessively by oral diseases,
      particularly periodontal disease. These are aggravated by poverty, poor living
      conditions, ignorance concerning health education, and lack of government funding
      and policy to provide sufficient oral health care workers. WHO and FDI have
      identified the problems and developed strategies. However, acceptable goals and
      standards of oral health have to be agreed. Furthermore, barriers to oral health
      promotion need to be overcome through co-operation at all levels and appreciation
      of cultural sensitivity. There is the need for research to determine which types
      of oral health care systems are most effective in reducing the extent of
      inequality in oral health. In developing countries where there are huge problems,
      intervention programmes focusing on primary care and prevention should be
      designed and implemented urgently and their effectiveness monitored and analysed
      scientifically. The WHO, FDI and national and international professional
      organisations should play a leading role in encouraging a determined, co
      ordinated effort towards improving the oral health status of disadvantaged people
      in developing countries.

PMID- 9779105
TI  - Awareness of periodontal diseases: the professional and the civil servant.
AB  - Newly qualified dentists and dental hygienists should have a good level of
      awareness of periodontal diseases. However, for a variety of reasons this
      knowledge may not be regularly updated or applied in practice. This paper
      considers how professional awareness can be influenced by such factors as:
      maintaining an up to date understanding of the nature of periodontal diseases,
      the routine use of appropriate screening and examination techniques, factors
      influencing assessment of treatment need, patient records, continuing
      professional education and an understanding of patient expectations. It goes on
      to describe how civil servants may help to stimulate improvements in awareness
      levels to periodontal diseases by promoting continuing education, epidemiological
      research and national oral health strategies as well as through legislation and
      regulation. The paper concludes that although a range of organisations can
      promote improvements in professional awareness, unless simultaneous efforts are
      made to improve the awareness of the general public to periodontal diseases, it
      is difficult to see how there can be an improvement in the periodontal health of
      the population.

PMID- 9779106
TI  - Practical periodontics. Awareness of periodontal disease--the patient.
AB  - This paper looks at awareness by the public and our patients' knowledge of the
      health of their gums and the tooth supporting tissues, what it means to them, how
      they interpret this information and whether they seek care as a result of such
      knowledge. The way a dentist and a patient interact with and without such
      knowledge is considered. It is contended that knowledge of the periodontal
      disease processes and of how to treat, manage, control, and even prevent must be
      accompanied by an awareness by the patient, the profession and industry. This
      recognises that the dentist and patient are in a partnership, especially in
      management of periodontal diseases.

PMID- 9779107
TI  - Awareness of periodontal disease--the role of industry.
AB  - Recently periodontal treatments have been performed intensively in daily clinical
      work and the definitive approach to periodontal therapy has been established in
      various types of periodontal diseases. It is no exaggeration to say that this is
      impossible without the co-operation of the dental industry. Furthermore, industry
      has also contributed greatly to the improvement of the 'quality of life',
      concerning masticatory function in the elderly. Both the progression of dental
      devices and the development of diagnostic methods have been considered to be the
      primary prerequisite for success in treatment and in the prevention of recurrence
      of the periodontal diseases. It is necessary that dental devices and medications
      for treatment should be developed corresponding to the advanced scientific
      evaluation of periodontal disease. This paper reviews our present knowledge about
      the role or contribution of industry to periodontology in terms of periodontal
      health care products, diagnostic kits, and therapeutic drugs.

PMID- 9779108
TI  - Practical periodontal screening and diagnosis.
AB  - The differences in approach between screening for and diagnosis of periodontal
      diseases are highlighted. The Periodontal Screening and Recording procedure is
      discussed in terms of its evolution and current application. For patients
      screened and found to have more advanced periodontal problems a panoramic dental
      radiograph with restricted supplemented periapicals are recommended. A
      comprehensive clinical periodontal examination should be performed for these
      patients, but it is argued that this may be performed after the initial hygiene
      phase of treatment. In establishing a diagnosis it is suggested that attention be
      paid to possible risk exposures. Newer, non-anatomic diagnostic procedures are
      discussed in principle and it is concluded that these do not have a practical
      application at present.

PMID- 9779109
TI  - Periodontal diagnosis: current status and future directions.
AB  - It is of concern to both public health agencies and health professionals to know
      whether the prevalence of periodontal diseases is increasing or decreasing in the
      world today. Unfortunately, the answer does not appear to be that simple.
      Clinical signs of inflammation are unable to reliably distinguish between non
      destructive forms of periodontal disease (gingivitis) and destructive forms
      (periodontitis). Physical assessments of damage to periodontal tissues, such as
      radiographic detection of bone loss or clinical attachment loss determined with a
      periodontal probe, measure damage from past episodes of destructive disease. New
      directions are needed to help to better diagnose periodontal diseases and some of
      the future possibilities are described and discussed.

PMID- 9779110
TI  - Effect of increased community and professional awareness of plaque control on the
      management of inflammatory periodontal diseases.
AB  - Data from CPITN studies indicate that severe periodontitis affects approximately
      10 per cent of most populations. These data have remained static for a number of
      years. Of interest, however, is that despite the dramatic increase in the use of
      oral hygiene aids, efforts by the dental profession in oral hygiene instruction,
      and the associated general improvement in oral hygiene levels in the community,
      the incidence of severe chronic inflammatory periodontal disease has remained
      largely unaffected. The effects of changing oral hygiene may be reflected in
      slight shifts in the mild and moderate classifications of periodontal disease but
      the prevalence of advanced disease in presumably susceptible subjects has
      remained relatively unchanged. The ramifications of relatively non-specific
      plaque control measures in the management of advanced disease in susceptible
      subjects are still unclear and it may not be until the adoption of a more
      specific approach to the control of specific pathogens which inhabit the
      subgingival biofilm that major changes in the general incidence of the severe
      inflammatory periodontal diseases will be seen.

PMID- 9779111
TI  - Modern supragingival plaque control.
AB  - Supragingival plaque control is essential for the maintenance of oral health.
      Despite the many chemotherapeutic agents available as mouthrinses and
      toothpastes, mechanical plaque removal is still the best method to achieve
      effective plaque control. This is due, in part, to the lack of development of
      oral antimicrobials with the effectiveness and substantivity of chlorhexidine
      gluconate but without its adverse effects of dental staining and calculus
      formation. The use of the numerous mechanical (manual and electric) oral hygiene
      devices extant and their effectiveness, however, are dependent upon patient
      dexterity and compliance and concomitant active professional treatment for the
      monitoring of home care, oral hygiene instruction and patient motivation. This
      paper evaluates the current methods available to reduce plaque and gingivitis
      with emphasis on their effectiveness at both supragingival plaque control and
      disease prevention. In addition, recent studies on the newer oscillating/rotating
      electric plaque removers and interdental cleaning devices will be discussed as
      related to their efficacy and compliance.

PMID- 9779112
TI  - The rationale for chemical adjuncts in plaque control.
AB  - The rationale for the adjunctive use of chemical anti-plaque agents depends on
      many factors in addition to the inherent antimicrobial properties of those
      agents. What is indicated generally is a basic oral hygiene regimen, as simple as
      it can be, bearing in mind the practical difficulties of getting people to clean
      their teeth optimally. Chemical adjuncts in many cases have the potential to
      simplify plaque control regimens. The mode of delivery may be critical to the
      success or otherwise of an adjunct. Adjuncts may simplify and accelerate the work
      of hygienists as well as patients. They may also serve to control plaque in
      severe forms of infectious inflammatory periodontal disease, as well as providing
      practical means of plaque control in the handicapped, or in those unable to
      practice optimal conventional home care oral hygiene. Chemical anti-plaque
      adjuncts offer a prospect of re-establishing the homeostasis of oral microbial
      biofilms fully consonant with the aims of modern periodontal medicine.

PMID- 9779113
TI  - Chemical treatment of periodontitis: local delivery of antimicrobials.
AB  - Periodontitis is a bacterial infection. It appears in a generalised form but more
      often appears in local areas in a patient's mouth or is reduced to localised
      areas by mechanical treatment. Periodontitis lends itself well to treatment by
      means of a controlled local delivery system using an antimicrobial agent. Several
      products have been introduced or are in the process of clearing regulatory
      agencies. It is the goal of all local delivery systems to deliver high
      concentrations of an antimicrobial directly to the site of the periodontal
      infection. Concentrations of medication can be achieved considerably higher than
      could be obtained with systemic administration, while the systemic uptake of the
      medication is minimal. Five local delivery systems (tetracycline fibre,
      doxycycline polymer, chlorhexidine chip, minocycline ointment and metronidazole
      gel) are now available. Techniques for their use and the supporting scientific
      evidence are presented and indications for the use of the various systems are
      also discussed. These local delivery systems offer the clinician additional
      therapeutic procedures to aid in the treatment of the chronic inflammatory
      periodontal diseases.

PMID- 9779114
TI  - Herbal medicine for periodontal diseases.
AB  - Traditional Chinese Medicine (TCM) is a treasure-house which has shown miraculous
      clinical effects. It has aroused tremendous interests in elucidating its
      mechanisms both in China and abroad. This paper presents a review of published
      articles on the effects and mechanisms of herbal medicine on periodontal disease.
      Specifically, two modifications of an ancient compound prescription were serially
      studied, Guchiwan (Tooth-firming pills) and Guchigao (Tooth-firming extract).
      Some in vitro studies have shown suppressive effects of various herbal extracts
      on bone resorption by isolated osteoclasts. TCM should be intensively studied for
      their possible use in periodontics.

PMID- 9779115
TI  - A review of guided tissue regeneration.
AB  - Developments in guided tissue regeneration mean that in certain circumstances it
      is possible, with predictable success, to create new connective tissue attachment
      to periodontally affected sites. Continuing development promises even greater
      progress in the future.

PMID- 9779116
TI  - The periodontist and the edentulous area--localised ridge augmentation.
AB  - The replacement of missing dentition by implant-borne dental restoration has been
      shown to be a highly predictable treatment method with good long-term prognosis.
      Subsequently, the use of implant-borne restorations has gradually increased over
      the use of conventional partial dentures and fixed restorations in recent years.
      Sufficient bone volume is the most important factor for successful implant-borne
      restoration, but often an insufficient amount of bone is found at implant sites.
      A new surgical approach to enlarge the width of alveolar crest was introduced by
      Buser et al. in 1996. This new approach is based on the principle of guided bone
      regeneration technique using a barrier membrane with autogenous bone grafts in
      the form of bone blocks, chips and particles. This promising new surgical
      technique allows placement of dental implants for implant-borne restorations in
      partially edentulous patients who were previously not considered to be implant
      candidates because of insufficient bone at the implant sites.

PMID- 9779117
TI  - Effect of calcium sulphate on the healing of periodontal intrabony defects.
AB  - The purpose of this series of three studies was to evaluate the regenerative
      potential of calcium sulphate in the treatment of periodontal intrabony defects.

PMID- 9779118
TI  - Periodontal needs of developing nations--the practitioner's view.
AB  - Periodontal health care is needed in developing as in developed countries. It is
      understood that many of the developing countries do not have the financial
      capabilities to provide such care. The model for developing periodontal care in
      communities that has been recommended by the Joint Working group of the FDI and
      the WHO Commission on Oral Health Research and Epidemiology offers a most
      promising means of providing developing nations with the building blocks that are
      needed to construct a rational periodontal health programme with the help and
      assistance of dental practitioners.

PMID- 9779119
TI  - Microbial contamination of dental unit waterlines: the scientific argument.
AB  - The quality of dental unit water is of considerable importance since patients and
      dental staff are regularly exposed to water and aerosols generated from the
      dental unit. The unique feature of dental chair water lines is the capacity for
      rapid development of a biofilm on the dental water supply lines combined with the
      generation of potentially contaminated aerosols. The biofilm, which is derived
      from bacteria in the incoming water and is intrinsically resistant to most
      biocides, then becomes the primary reservoir for continued contamination of the
      system. Dental water may become heavily contaminated with opportunistic
      respiratory pathogens such as Legionella and Mycobacterium spp. The significance
      of such exposure to patients and the dental team is discussed. There is at the
      present time, no evidence of a widespread public health problem from exposure to
      dental unit water. Nevertheless, the goal of infection control is to minimise the
      risk from exposure to potential pathogens and to create a safe working
      environment in which to treat patients. This paper evaluates the range of
      currently available infection control methods and prevention strategies which are
      designed to reduce the impact of the biofilm on dental water contamination, and
      are suitable for use in general practice. Bacterial load in dental unit water can
      be kept at or below recommended guidelines for drinking water (less than 200
      colony forming units/ml) using a combination of readily available measures and
      strict adherence to maintenance protocols. Sterile water should be employed for
      all surgical treatments.

PMID- 9779120
TI  - An investigation of the disposal of dental clinical waste in Bangkok.
AB  - This study investigated the disposal of clinical waste within dental surgeries in
      Bangkok, Thailand and followed the waste trail to the rubbish tips. A
      questionnaire was sent to all dental practices in the Bangkok Metropolitan Area.
      The response rate was 57.7 per cent. At the same time, rubbish collectors and
      scavengers were interviewed to see if they encountered clinical dental waste. Few
      dentists complied with all recommendations for the disposal of waste. Most waste
      was disposed of into the domestic rubbish stream. Rubbish collectors and
      scavengers knew what dental rubbish looked like and some had had needle-stick
      injuries. Although recommendations can be made to the dental profession to alter
      their behaviour, real improvement is unlikely without changes to legislation and
      social policy.

PMID- 9779121
TI  - Reasons for taking radiographs in general dental practice in Dar-es-Salaam,
      Tanzania.
AB  - This study investigated the reasons why dental practitioners at the Muhimbili
      Dental OPD clinic in Dar-es-Salaam take radiographs. Information was obtained
      from medical records at the Department of Dental Radiology for an eighteen month
      period, during which 28,171 patients were seen at the hospital, and of which
      2,672 (9.48 per cent) were radiographed. The main reasons for taking radiographs
      (percentages) was to detect fractures (17.2), tumours (14.1), caries (12.5),
      impacted teeth (12.2), periodontal disease (11.3), and non-specific dental pain
      (10.4). Radiographs were also taken for orthodontic (7.0 per cent) and endodontic
      (6.8 per cent) reasons. Some of the reasons for taking radiographs such as
      hypersensitive teeth, apicectomy, neuralgia and xerostomia were previously
      unheard of, indicating an increasing diversity of dental services. In conclusion,
      there is a need to increase the utilisation of dental radiographs from the
      present modest level in order to meet the growing need of the increasingly
      informed dental population in Dar-es-Salaam.

PMID- 9779122
TI  - Comparison of two indices of caries patterns in 3-6 year old Brazilian children
      from areas with different fluoridation histories.
AB  - The purpose of this study was to define the pattern of caries in 3-6 year old
      children from two districts in Araraquara, SP, Brazil, fluoridated for more than
      10 years and from a much more recently fluoridated one in the same city, using
      two different indices. The study included 1,066 children (903 from the two first
      districts and 163 from the third). Patterns of disease were described in terms of
      prevalence and dmft in molars, incisors (and/or canines) individually and
      together. Pattern was also described according to the 'caries analysis system'.
      In both areas the majority of 3-4 year olds had disease confined to primary
      molars. In the areas fluoridated for more than 10 years, the highest proportion
      of 5-6 year olds with caries also had the disease confined to primary molars (36
      per cent) but in the more recently fluoridated area, similar proportions of
      children had caries in primary molars alone as had caries in both primary molars
      and incisors (40 per cent and 44 per cent, respectively). Results according to
      the 'caries analysis system' showed that in both areas the prevalence of fissure
      caries and posterior bucco-lingual surface pattern in 5-6 year olds were twice as
      great as those observed in 3-4 year olds. Differences between the areas were
      obvious whichever method was used to define pattern, confirming the benefits of
      water fluoridation. The simpler method of grouping tooth type affected showed the
      differences as effectively as the more complex 'caries analysis system'.

PMID- 9779123
TI  - Guided tissue regeneration update.
AB  - The ultimate goal of periodontal therapy is to restore periodontal tissues lost
      through disease or trauma. The most predictable way to accomplish this goal is by
      guided tissue regeneration (GTR). The principle of GTR is to give preference to
      certain cells to repopulate the wound area to form a new attachment apparatus.
      Clinically this is accomplished by placing a barrier over the defect thereby
      excluding gingival tissues from the wound during early healing. The first
      generation of GTR barriers were non-resorbable which implies that they have to be
      removed in a second surgical procedure. Resorbable barriers have recently been
      introduced, changing GTR into a single-step procedure. Periodontal defects that
      will predictably benefit from GTR therapy are intrabony, furcation class II and
      gingival recession defects. This paper reviews the scientific evidence of what
      can be achieved by GTR procedures for various periodontal defects as well as
      factors of importance to increase the predictability of a successful treatment
      outcome.

PMID- 9779124
TI  - What do the public and profession know about dental caries prevention in Korea?
AB  - The availability of known preventive dental measures has no value, unless they
      are used appropriately by the public and by dental health care providers.
      Nevertheless, there is a wide gap between what is known about preventive
      procedures and dental public health measures in the preventive and public health
      dental world and what is known and used by the public and dental health care
      providers in Korea. The gap should be minimised to enable dental caries to be
      conquered. Firstly, an emphasis on the appropriate use of preventive procedures
      is needed in colleges of dentistry, dental hygienist training technical colleges
      and continuing educational courses. Simultaneously, there should be reform of the
      state run qualifying examinations for dentists and for dental hygienists in order
      to upgrade preventive and public health dentistry. Meanwhile, to promote personal
      dental health, introduce community preventive dental measures and maintain their
      use through self-help personal efforts and organised combined efforts, all dental
      health care providers have to educate the public. In addition, dental health care
      providers and the public should be regularly questioned on their knowledge,
      opinions and practices about community water fluoridation programmes, school
      based fluoride mouthrinsing programmes and preventive procedures at an interval
      of several years, as a test to measure the achievements of dental educational and
      dental health education aims.

PMID- 9779125
TI  - A comparison of DAI scores and characteristics of occlusal traits in three ethnic
      groups of Asian origin.
AB  - The Dental Aesthetic Index (DAI) is an orthodontic index based on socially
      defined aesthetic standards. The primary aim of this study was to compare the
      prevalence of malocclusion using the DAI among three ethnic groups of Asian
      origin; Japanese, Chinese in Taiwan and Native Americans with white Americans. A
      secondary goal was to consider the possibility that genetic factors might be the
      cause of the characteristics of malocclusion in the ethnic groups of Asian
      origin. Malocclusion was evaluated in 1029 Japanese and 176 Chinese in Taiwan
      students utilising the DAI, and the findings were compared with those of Native
      Americans and white Americans. The DAI values of Japanese and Native Americans
      were significantly higher than those of Chinese in Taiwan and white Americans.
      The mean DAI values showed no common tendency among the three ethnic groups. The
      characteristics of malocclusion in each ethnic group were also evaluated by
      analysis of each of the 10 DAI component scores. The results revealed common
      characteristics of malocclusion in the three ethnic groups of Asian origin using
      white Americans as the standard. The findings in the present study suggest the
      possibility that genetic factors might have an influence on the characteristics
      of malocclusion.

PMID- 9779126
TI  - Developing appropriate dental education systems: the impact of changes in oral
      health status and oral health care systems.
AB  - Current education programmes for oral health care workers have failed to adapt to
      the changing oral health status and the changing demands made upon oral health
      care systems. In order to adapt, education systems need to recognise the forces
      that are influencing the demands on the oral health care system and identify the
      most appropriate solutions. The most logical solution is to develop programmes
      which reflect the Primary Health Care Approach (PHCA), and in particular
      emphasise inter-sectorial collaboration. The challenge for dental education
      systems is to identify mechanisms through which these principles can be applied.

PMID- 9779127
TI  - Cerebral hemodynamic changes during sustained hypocapnia in severe head injury:
      can hyperventilation cause cerebral ischemia?
AB  - Hyperventilation (HV) is routinely used in the management of increased
      intracranial pressure (ICP) in severe head injury. However, this treatment
      continues to be controversial because it has been reported that long-lasting
      reduced cerebral blood flow (CBF) due to profound sustained hypocapnia may
      contribute to the development or deterioration of ischemic lesions. Our goal in
      this study was to analyze the effects of sustained hyperventilation on cerebral
      hemodynamics (CBF, ICP) and metabolism (arterio jugular differences of lactates =
      AVDL). CO2-reactivity and CBF was estimated using AVDO2 (arteriojugular
      differences of oxygen content). Global cerebral ischemia and increased anaerobic
      metabolism were considered according to AVDO2 and AVDL respectively. Thirty-three
      patients with severe and moderate head injury and increased ICP were included.
      Within 72 hours after accident, patients were hyperventilated for a period of 4
      hours. During this time jugular oxygen saturation (SjO2), arterial oxygen
      saturation (SaO2), ICP, mean arterial blood pressure (MABP), AVDO2 and AVDL were
      recorded. In our study, most patients preserved CO2-reactivity (88.2%). In these
      cases HV was very effective in lowering ICP. Our findings showed that this
      reduction was due to a CBF decrease. According to basal AVDO2 twenty-five
      patients (75.7%) were considered as hyperemic and eight (24.2%) as not hyperemic.
      Global ischemia and increased anaerobic metabolism were detected in one case in
      the non-hyperemic group. According to AVDO2 and AVDL, no adverse effects were
      found during four hours of HV in hyperemic patients. Nevertheless, AVDO2 and AVDL
      are global measurements and might not detect regional ischemia surrounding focal
      lesions such as contusions and haematomas. We suggest that monitoring of AVDO2 or
      other haemometabolic variables should be mandatory when sustained HV is used in
      the management of head injury patients.

PMID- 9779128
TI  - Use of vasopressors to raise cerebral perfusion pressure in head injured
      patients.
AB  - Cerebral ischemia due to low cerebral perfusion pressure (CPP) is the most
      important secondary effect of severe head injury. There is consensus regarding
      the maintenance of this pressure at levels above 70 mm Hg. One way to elevate CPP
      is by increasing mean arterial pressure (MAP). In this study, the authors attain
      this target by using adrenergic vasopressors investigating the effectiveness of
      dopamine, noradrenaline and methoxamine in 16 severe head injured patients. The
      results were: a) the increase of MAP effectively increased CPP without changes in
      intracranial pressure (ICP) and cerebral extraction of oxygen (CEO2); b)
      noradrenaline at a dose of 0.5 mg to 5 mg/h was effective and safe and might be
      considered the drug of choice; c) dopamine was not as effective at a high dose of
      10 to 42.5 micrograms/kg/min; d) methoxamine given as a bolus was an effective
      way to control sudden decreases in MAP. It made the patients more responsive to
      dopamine. No important undesirable reactions occurred during the study.

PMID- 9779129
TI  - Effects on intracranial pressure of fentanyl in severe head injured patients.
AB  - Despite opioids are routinely used for analgesia in head injured patients, the
      effects of such drugs on ICP and cerebral hemodynamics remain controversial.
      Cerebrovascular autoregulation (CAR) could be an important factor in the ICP
      increases reported after opioid administration. In order to describe the effects
      on intracranial pressure of fentanyl and correlated such effects with
      autoregulation status, we studied 30 consecutive severe head injury patients who
      received fentanyl (2 micrograms/kg) intravenously over one minute. Prior to
      study, CAR was assessed. Monitoring included MAP, HR, SaO2, ETCO2, SjO2 and ICP.
      Changes in cerebral blood flow (CBF) were estimated from relative changes in
      AVDO2. Patients mean GCS was 5.7 +/- 1.7 (mean +/- STD) and mean ICP on admission
      was 23.8 +/- 16.3 mmHg. Fentanyl caused significant increases in ICP and
      decreases in MAP and CPP, but CBF remained unchanged when estimated by AVDO2. In
      patients with preserved CAR (34.5%), opioid-induced ICP increase was greater (but
      not statistically significant) than in those with impaired CAR (65.5%). We
      conclude than fentanyl moderately increased ICP and decreased MAP and CPP. Our
      data suggests that in patients with preserved CAR, potent opioids could cause
      greater increases of ICP, probably due to activation of the vasodilatadory
      cascade.

PMID- 9779130
TI  - The possible role of CSF hydrodynamic parameters following in management of SAH
      patients.
AB  - It is suggested that reduced intracranial compliance may be present even when
      measured ICP is normal and may precede clinical deterioration. Our findings
      reflect a decompensation of hydrodynamic parameters more pronounced 4-7 postictal
      days, when compliance is reduced not only in patients with poor clinical
      condition, but also in patients with Hunt-Hess grade I-III. Increased CSF outflow
      resistance in the first few days is not surprising; it is thought to be due to
      the blockage of flow of CSF through the basal subarachnoid cisterns and clogging
      of the arachnoid villi with erythrocytes and fibrin. Enlargement of ventricles
      seen on CT scan at the same time suggests the development of acute hydrocephalus.
      During the first days after SAH, our data reflects evidence of ventricular
      enlargement in patients presenting with both poor and better clinical condition.
      We conclude that the monitoring of ICP and dynamic measuring of CSF hydrodynamic
      parameters is important for longer than the generally accepted few days for
      selected cases after SAH.

PMID- 9779131
TI  - Decompressive craniectomy in patients with uncontrollable intracranial
      hypertension.
AB  - There has been controversial discussion about the benefits of decompressive
      craniectomy in patients with critically raised intracranial pressure (ICP) after
      severe head injury. The aim of this retrospective study was to analyze the
      results of secondary decompressive craniectomy in patients with uncontrollable
      raised ICP after maximum aggressive medical treatment. The data of 28 patients
      (mean age 22 years, range 8-44 years) with severe head injury and posttraumatic
      cerebral edema were analyzed retrospectively. Surgery was not indicated in
      patients with vast primary lesions, hypoxia, ischemic infarction, brainstem
      injuries and central herniation. The outcome was classified according to the
      Glascow Outcome Scale (GOS) after one year. The decompressive crainectomy was
      performed an average of 68 hours after trauma, and ICP (< 25 mm Hg) decreased
      always while cerebral perfusion pressure (CPP > 75 mm Hg) improved as well as
      cerebral blood flow and microcirculation to normal values. 15 patients (56%) had
      a good outcome after one year (GOS 4 + 5). 5 patients (18%) were severely
      disabled, 4 patients (14%) remained in vegetative state and 3 patients (11%)
      died. Decompressive craniectomy should be kept in mind as the last therapeutic
      step, especially in young patients with head injury and raised ICP, which is not
      controllable with conservative methods.

PMID- 9779132
TI  - A comparison of the effects of norepinephrine, epinephrine, and dopamine on
      cerebral blood flow and oxygen utilisation.
AB  - The concomitant effects of infusions of catecholamines on cerebral blood flow
      (CBF), intracranial pressure (ICP), arterio-venous oxygen content difference
      (AVDO2), and cerebral oxygen utilization (COU) were prospectively studied in an
      intact cerebral autoregulatory model. Epinephrine, norepinephrine and dopamine
      were infused at doses used in clinical practice in awake, chronically
      catheterized sheep (n = 5). Mean arterial pressure (MAP), CBF and ICP were
      measured continuously, COU was expressed as delta CBF x AVDO2. All 3 drugs
      significantly increased MAP in a dose dependent manner. Norepinephrine and
      epinephrine had no significant effects on ICP, CBF, AVDO2 or COU at infusions of
      0-60 micrograms/min. Infusions of dopamine from 0-60 micrograms/kg/min resulted
      in statistically significant increases in ICP (+34.5 +/- 3.7 to +97.2 +/- 6.8)
      and CBF (+13.3 +/- 3.2 to +52.6 +/- 24.3) (% change baseline +/- SEM, 95% CI,
      ANOVA), reduction in AVDO2 (3.54 +/- 0.2. to 2.69 +/- 0.2 mg%) and a biphasic
      response in COU. In the intact physiological model, induced hypertension by
      epinephrine and norepinephrine is not associated with global changes in CBF, ICP
      or COU which remain constant. At equivalent doses, dopamine causes cerebral
      hyperaemia, increased ICP and increased global cerebral oxygen utilization.

PMID- 9779134
TI  - Incidence of intracranial hypertension after severe head injury: a prospective
      study using the Traumatic Coma Data Bank classification.
AB  - Intracranial hypertension (ICH) is a frequent finding in patients with a severe
      head injury. High intracranial pressure (ICP) has been associated with certain
      computerized tomography (CT) abnormalities. The classification proposed by
      Marshall et al. based on CT scan findings, uses the status of the mesencephalic
      cisterns, the degree of midline shift, and the presence or absence of focal
      lesions to categorize the patients into different prognostic groups. Our aim in
      this study was to analyze the ICP evolution pattern in the different groups of
      lesions of this classification. PATIENTS AND METHODS: We present the results of a
      prospective study in 94 patients with severe head injury, in whom ICP was
      monitored for at least 6 hours. ICP evolution was classified into three different
      categories: 1) ICP always < 20 mm Hg, 2) Intracranial hypertension at some time
      during monitoring, but controlled by medical or surgical treatment, 3)
      Uncontrollable ICP. The ICP pattern was correlated with the final CT diagnostic
      category. CONCLUSIONS: 3 patients had a normal CT scan, and none of them
      presented intracranial hypertension. In diffuse injury type II, the ICP evolution
      may be quite different. Patients with bilateral brain swelling (Diffuse Injury
      III) have a high risk of increased ICP (63.2%). Although in our study the
      frequency of Diffuse Injury IV was low, all patients in this category had a
      refractory ICP. In the category of evacuated mass lesions, two thirds of the
      patients presented an intracranial hypertension. In one third, ICP was refractory
      to treatment. 85% of patients with a non-evacuated mass lesion showed an
      increased ICP.

PMID- 9779133
TI  - Comparative effects of hypothermia, barbiturate, and osmotherapy for cerebral
      oxygen metabolism, intracranial pressure, and cerebral perfusion pressure in
      patients with severe head injury.
AB  - In order to select the optimal neurointensive treatment for patients with severe
      head injury and intracranial hypertension, the effects of hypothermia (HT),
      barbiturates (BT), and osmotic agents (OT) on focal and diffuse cerebral oxygen
      metabolism were evaluated by means of continuous monitoring of bifrontal regional
      oxygen saturation (rSO2), jugular bulb oxygen saturation (SjO2), jugular bulb
      temperature (Tjb), intracranial pressure (ICP), and cerebral perfusion pressure
      (CPP). PATIENTS AND METHODS: Cerebral oxygen metabolism in SjO2 and rSO2, ICP,
      CPP, and Tjb were continuously monitored in severe head injury patients with
      Glasgow Coma Scale < 8, ages 10-62: 13 with focal and 10 with diffuse injuries.
      The effects of BT (n = 6), HT (n = 9), and OT (n = 8) on these parameters
      (ICP/CPP, SjO2, and rSO2) were compared. Evaluations were performed in terms of:
      a) Percentage of abnormal values based on normal control values; ICP < 20 mm Hg,
      CPP > 60 mm Hg, SjO2 55-75%, and rSO2 60-80% were calculated, b) Effects of
      pentobarbital dose (mg/kg/h) for the parameters compared among < 1.0, 1.1-2.0,
      2.1-3.0, and > 3.1. c) Effects of Tjb (degree C) on parameters compared among
      hyperthermia (> 38 degrees C), normothermia (36-37.9 degrees C), mild hypothermia
      (34-35.9 degrees C) and moderate hypothermia (< 33.9 degrees C). RESULTS: a)
      Abnormal data differed significantly among the three treatment groups. rSO2
      showing ischemia on the affected side was more marked in BT than in HT or OT. b)
      ICP decreases and CPP increases correlated significantly with the pentobarbital
      dose. c) ICP decreases and CPP increases correlated significantly with decreased
      Tjb. CONCLUSION: The therapeutic effects of hypothermia, barbiturates, and
      osmotherapy on cerebral oxygen metabolism and ICP/CPP are different according to
      the underlying pathological lesions of patients with severe head injury.

PMID- 9779135
TI  - Treatment of elevated intracranial pressure by infusions of 10% saline in
      severely head injured patients.
AB  - The management of intracranial pressure (ICP) is a factor in outcome of patients
      with head trauma. However, recent studies have revealed that the current
      strategies, which have been applied to control ICP for adequate cerebral
      perfusion, are unsatisfactory. Against this background, the efficacy of short
      term infusions of hypertonic saline on ICP was investigated. In severely head
      injured (SHI) patients, hypertonic saline (100 ml 10% NaCl) was administered when
      standard agents (mannitol, sorbitol, THAM) failed in reducing ICP. To evaluate
      the pressure reduction after saline infusions the resulting ICP relaxations were
      analysed statistically in respect to the parameters amplitude, duration and
      dynamic behaviour of the ICP responses. In 42 randomized relaxations, the
      relative ICP decrease was 43% [28%-58%] (median [interquartile range]). The
      corresponding pressure drop was 18 mmHg [15-27 mm Hg]. Relaxations lasted for 93
      min [64-126 min] and a relative ICP minimum was reached 26 min [12-33 min] after
      infusion. In the individual cases the temporal course of the parameters amplitude
      and decline interval depict a tendency toward lower and higher values,
      respectively, under conditions of a generally increasing ICP. As expected, the
      infusion of hypertonic saline reduces ICP in patients suffering from SHI. The
      pressure drop, duration and dynamic behaviour are suspected to depend both on the
      pressure level to reduce and concomitant medications.

PMID- 9779136
TI  - Pharmacokinetics of serum glycerol and changes of ICP: comparison of gastric and
      duodenal administration.
AB  - To investigate the more effective route of oral administration of glycerol to
      decrease the raised ICP, two different routes were employed in the clinical
      practice. The one was through a Naso-Gastric tube, and the other was through an
      Entero-Duodenal tube. Pharmacokinetics of glycerol in relation to the decrease of
      ICP, and the changes of other parameters which could influence the serum osmotic
      pressure were sequentially monitored for initial 30 minutes. In the group of
      Entero-Duodenal route, the time to reach to the maximum glycerol concentration
      (Tmax) was faster, the maximum concentration of glycerol (Cmas) was higher, and
      ICP reduction rate was greater than these in the group of Naso-Gastric route.
      Other parameters (Na, K, BUN and Glucose) showed no significant difference
      between the two routes. It can be concluded that the Entero-Duodenal
      administration of glycerol is the more effective route to decrease the raised
      ICP, when it is administered orally.

PMID- 9779137
TI  - External lumbar drainage in uncontrollable intracranial pressure in adults with
      severe head injury: a report of 7 cases.
AB  - The retrospective results of external lumbar drainage in 7 adult patients with
      severe closed head injury and intracranial pressure (ICP) refractory to
      aggressive management strategies are presented. All patients had Glasgow Coma
      Scale (GCS) scores of 8 or less within 24 hours after admission and were treated
      by a staircase protocol including sedation, ventricular drainage,
      hyperventilation and mannitol. In three cases barbiturate drugs and an
      artificially induced hypothermia were used. Four patients required surgical
      evacuation of mass lesions. Three patients made a good functional recovery, 2
      were severely disabled and 2 patients died. In none of the patients clinical
      signs of cerebral herniation occurred. We recommend additional external lumbar
      drainage in adults with severe head injury unresponsive to aggressive ICP control
      with open basilar cisterns and absent focal mass lesions on computerized
      tomography scan before drainage.

PMID- 9779138
TI  - ICP-CBF trauma bolt, laboratory evaluation.
AB  - Thermal diffusion flowmetry is a continuous quantitative technique of measuring
      regional cerebral blood flow utilizing a silastic strip probe placed through a
      craniotomy or craniectomy in the operating room. A new bolt like application of
      this technology is now available for commercial use and is especially designed
      for bedside placement in trauma patients. This new trauma bolt is tested in
      juvenile pigs who are subjected to episodes of hypercapnea to increase cerebral
      blood flow, and records significant changes in blood flow. Another feature of the
      trauma bolt is a second port for the placement of an intracranial pressure (ICP)
      monitor. Placement of the probe and ICP monitor were easier than with the
      silastic probe and had relatively little complication.

PMID- 9779139
TI  - Bilateral ICP monitoring: its importance in detecting the severity of secondary
      insults.
AB  - The aim of head injury management is to prevent secondary insults to the damaged
      brain. Raised intracranial pressure and low cerebral perfusion pressure are two
      secondary insults which are important determinants of outcome following severe
      head injury (SHI). Traditionally ICP is measured in the right frontal region in
      an attempt to minimise the effects and complications of transducer placement.
      This assumes that the brain acts like a fluid and that ICP is transmitted equally
      throughout the intracranial space. Experimental studies suggest that this is not
      the case: expanding mass lesions are associated with the development of ICP
      gradients. Ten patients with SHI who had an unilateral mass lesion confirmed on
      CT were studied. All had bilateral placement of intraparenchymal Camino ICP
      transducers in the frontal regions. Data from both transducers were recorded
      every two minutes and stored electronically. The volume of the mass lesion was
      calculated from the CT scan. Significant and lasting ICP gradients between
      hemispheres were found in all patients with an acute subdural haematoma (greater
      than 10 mmHg for longer than 10 minutes). Such differences were not found in
      patients with intracerebral haematoma or contusions. We would advocate that ICP
      is recorded IPSILATERAL to the lesion in patients with SHI due to acute subdural
      haematoma.

PMID- 9779140
TI  - Clinical evaluation of the Codman microsensor intracranial pressure monitoring
      system.
AB  - INTRODUCTION: The use of the Camino fibre-optic subdural device for measuring
      Intracranial Pressure (ICP) in patients, has been shown to correlate well with
      recordings from the "gold standard" intraventricular fluid filled catheter [1].
      Following this work, its use has become standard in the clinical monitoring of
      patients. More recently, laboratory studies have demonstrated accuracy,
      acceptable drift and high fidelity for the new Codman Microsensor ICP Transducer,
      a miniature strain gauge mounted on a flexible nylon catheter [3]. Its
      performance in patients, however, has yet to be fully assessed, in comparative
      studies. METHODS: Eight patients (5 head injured, 3 with an Intracerebral
      haematoma) had a Codman Microsensor inserted. A Camino Transducer was fitted
      immediately adjacent to it. A computerised system was used to continuously record
      both ICP readings. RESULTS: In total 140,323 recordings were made over a wide
      range of ICP values. Study periods ranged from 0.5 to 116 hours. In one patient
      the Codman transducer tracing failed after several days, probably due to fracture
      of electrical cable close to the interface box. The readings from the two ICP
      transducers were compared on Time Series, logistic regression and Altman-Bland
      plots. Drift of the ICP recorded by the Codman microsensor, was noted in 2
      patients, 1 in positive direction (maximum 30 mmHg), 1 negative (max. 20 mmHg).
      In both cases the Camino ICP recording was relatively stable. In 24% of the
      recordings the Codman microsensor recorded ICP as 5 or more mmHg greater than the
      Camino, this difference was 10 mmHg or greater in 9% of recordings. Conversely
      the Camino recording was 5 mmHg or more, than the Codman, in 5% of all
      recordings, and 10 mmHg or more in 3%. CONCLUSION: These differences could in the
      majority of cases (excepting the negative drift) be explained by a constant
      offset of the Codman transducer, as described previously [6]. Further examination
      of this device is required.

PMID- 9779141
TI  - Cerebral monitoring devices: analysis of complications.
AB  - The use of indwelling cerebral monitoring devices (ICMDs) is common in the
      intensive care of neurosurgical patients. ICMDs are used to measure and treat
      intracranial pressure (ICP), temperature, blood flow and the microchemical
      environment. Intracranial hemorrhage (ICH) and infection are risks of ICMD use
      [4]. This study presents ICMD use at Detroit Receiving Hospital (DRH) from July
      1993- March 1997. Analysis of complications associated with ICMD placement will
      test the hypothesis that complication rate depends upon type of ICMD used. A log
      of all patients having ICMDs at DRH has been kept since 1993. This log was used
      to identify complications of ICMD placement. Each case was reviewed and the
      following data obtained: diagnosis, patient age, initial Glasgow Coma Score,
      Glasgow Outcome Score, type of ICMD, number of ICMDs per patient, duration of
      implant and complication. Descriptive and non-parametric statistics were used to
      compare samples of interest. The following number of ICMDs were placed: 274
      ventriculostomies, 229 Camino intra parenchymal ICP monitors, and 33 other ICMDs.
      Complications in these 536 cases include 21 infections, 15 ICHs, 1 granuloma and
      1 persistent cerebrospinal fluid leak. Complication was analyzed as a function of
      ICMD type using Chi-Square test for independence. The rate of infection and ICH
      was significantly higher in the ventriculostomy group (p = 0.0001). These results
      support the hypothesis that complications of ICMD use are due to the type of
      device implanted. The determinants of ICMD complication is undoubtedly
      multifactorial. The clinician must consider the complication rate related to a
      particular ICMD among other factors when choosing to place an ICMD.

PMID- 9779143
TI  - Anterior fontanelle pressure recording with the Rotterdam transducer: variation
      of normal parameters with age.
AB  - Using a reliable non-invasive technique for ICP monitoring, we realized 93
      continuous anterior fontanelle pressure (AFP) recordings in 86 healthy infants
      aged from 29 to 85 post-conceptional (PC) weeks. For each recording, we
      calculated the mean and extremes values of AFP, cerebral pulse amplitude, and
      pressure waves rate and amplitude. We observed the occurrence of plateau-waves of
      relatively low amplitude and duration in most infants aged of more than 49 PC
      weeks. We postulate that PW represents a physiological phenomenon which is
      amplified under pathological conditions. All AFP parameters are correlated to PC
      age and vary during early infancy according to an ascending sigmoidal relation
      (this variation may be explained by a connection between several cranio-cerebral
      characteristics of the young infant). We conclude that the interpretation of AFP
      recordings must take into account [1] PC age rather than postnatal age, [2]
      variation of AFP parameters with age, and [3] occurrence of physiological plateau
      waves.

PMID- 9779142
TI  - Comparison of percutaneous ventriculostomies and intraparenchymal monitor: a
      retrospective evaluation of 156 patients.
AB  - Intraventricular catheters (IVC) and Intraparenchymal fiberoptic catheters (IPC)
      are the prevalent methods of intracranial pressure (ICP) monitoring. This study
      assesses the complications caused by either method. Previous studies have shown a
      higher complication rate with IVC. In 156 consecutive patients, with IVC (n =
      104) or IPC (n = 52) insertion, the demographics, Glasgow coma score (GCS), ICP,
      duration of monitoring, changes in monitoring device, complications and
      computerized tomography findings, were recorded. The patients were categorized
      into severe (GCS 3-8), moderate (GCS 9-12) and mild (GCS 13-15) groups. A
      retrospective, comparative analysis of both techniques was conducted, using
      Kruskal-Wallis one way analysis of variance with chi square approximation and
      Mann-Whitney U tests. The use of IPC at 86.5% predominated in patients with GCS 3
      8, while IVC at 81.4% and 92% prevailed in GCS groups 9-12 and 13-15,
      respectively (p = 0.000). 43.2% IVC were used for 10+ days and 25.9% for 1-3
      days, while 80% of IPC were used for less than 6 days (p = 0.000). The
      complication rate for IVC and IPC was 25% vs 4.4% (p = 0.000). The infection rate
      was 4.4% and 0.6% (p = 0.1) while, inadvertent removal 4.4% vs 1.2% (p = 0.4),
      respectively. Malpositions occurred only with IVC (20.1%). All documented
      complications were without untoward clinical sequelae. We conclude that, IVC
      remains comparable to IPCs in complications.

PMID- 9779144
TI  - Interhemispheric pressure gradients in severe head trauma in humans.
AB  - Interhemispheric pressure gradients may occur following severe head trauma in
      patients even in the absence of intracranial space occupying lesions. A higher
      ICP of the contralateral hemisphere may escape routine unilateral ICP monitoring.
      Clinical signs and CT scans do not seem to predict reliably a lateralized ICP.
      According to our data with a limited number of patients, interhemispheric
      pressure gradients seem to occur in the initial posttraumatic phase in some
      patients, and they seem to resolve following adequate ICP treatment after several
      hours. Therefore, simultaneous bilateral ICP measurement may be warranted in the
      initial posttraumatic phase.

PMID- 9779145
TI  - An avoidable methodological failure in intracranial pressure monitoring using
      fiberoptic or solid state devices.
AB  - Failure of intraventricular pressure (IVP) measurement in case of catheter
      blockage is believed to be eliminated by using intraventricular microtransducers.
      We report about an avoidable methodological error, which may affect the
      reliability of IVP measurement with these devices. Intraventricular fiberoptic or
      solid state devices were implanted in 43 patients considered to be at risk for
      catheter occlusion. Two different types were used: devices where the transducer
      is placed inside the ventriculostomy catheter (Type A), and devices where the
      transducer is integrated in the external surface of the catheter (Type B). Of the
      15 patients treated with Type A devices, no reliable pressure recording could be
      obtained in three patients where ventricular puncture was not successful. In four
      cases of the remaining 12 patients, periods of erroneous pressure readings were
      revealed. After opening of CSF drainage, all Type A devices failed to reflect
      real IVP. In patients treated with Type B devices, no erroneous pressure
      recording could be identified, irrespective if CSF drainage was performed or not.
      Transducers, which are simply placed inside the ventriculostomy catheter require
      fluid coupling. They may fail, either during CSF drainage or when the catheter is
      blocked or placed within the parenchyma.

PMID- 9779146
TI  - Influence of hyperventilation on brain tissue-PO2, PCO2, and pH in patients with
      intracranial hypertension.
AB  - A harmful effect of prolonged hyperventilation on outcome has been shown in
      comatose patients after severe head injury. The purpose of this study was to
      assess the acute effect of moderate hyperventilation for treatment of
      intracranial hypertension (ICP < 20 mmHg) on invasively measured brain tissue-PO2
      (PtiO2), PCO2 (PtiCO2) and pH (tipH) in severely head injured patients. 15
      severely head injured patients (GCS < or = 8) were prospectively studied.
      Intracranial pressure (ICP), mean arterial blood pressure (MABP), cerebral
      perfusion pressure (CPP), endtidal CO2 (ETCO2), PtiO2, PtiCO2 and tipH (Paratrend
      or Licox microsensors) were continuously recorded using multimodal monitoring.
      Following a baseline period of 15 minutes, patients were hyperventilated for 10
      minutes. Arterial blood gas analysis was done before, during and after
      hyperventilation. At least three hyperventilation maneuvers were performed per
      patient. For statistical analysis the Friedman test was used. Hyperventilation
      (paCO2: 32.4 +/- 0.6 to 27.7 +/- 0.5 mmHg) significantly reduced ICP from 25.3 +/
      1.5 to 14.2 +/- 1.9 mmHg (p < 0.01). As a consequence, CPP increased by 9.6 +/-
      3.4 mmHg to 76.8 +/- 3.2 mmHg. Brain tissue PCO2 decreased from 37.5 +/- 1.3 to
      34.6 +/- 1.2 while tipH increased from 7.13 to 7.16. In all patients,
      hyperventilation led to a reduction of brain tissue PO2 (PtiO2/Licox: 24.6 +/-
      1.4 to 21.9 +/- 1.7 mmHg, n.s.; PtiO2/Paratrend: 35.8 +/- 4.3 to 31.9 +/- 4.0
      mmHg, n.s.). In one case hyperventilation even had to be stopped after 7 min
      because the drop in brain tissue PO2 below 10 mmHg signalized imminent hypoxia.
      As well known, hyperventilation improves CPP due to a reduction in ICP. However,
      this does not ameliorate cerebral oxygenation as demonstrated by the decrease in
      PtiO2. This underlines that hyperventilation should only be used with caution in
      the treatment of intracranial hypertension.

PMID- 9779147
TI  - Noninvasive measurement of pulsatile intracranial pressure using ultrasound.
AB  - The present study was designed to validate our noninvasive ultrasonic technique
      (pulse phase locked loop: PPLL) for measuring intracranial pressure (ICP)
      waveforms. The technique is based upon detecting skull movements which are known
      to occur in conjunction with altered intracranial pressure. In bench model
      studies, PPLL output was highly correlated with changes in the distance between a
      transducer and a reflecting target (R2 = 0.977). In cadaver studies, transcranial
      distance was measured while pulsations of ICP (amplitudes of zero to 10 mmHg)
      were generated by rhythmic injections of saline. Frequency analyses (fast Fourier
      transformation) clearly demonstrate the correspondence between the PPLL output
      and ICP pulse cycles. Although theoretically there is a slight possibility that
      changes in the PPLL output are caused by changes in the ultrasonic velocity of
      brain tissue, the decreased amplitudes of the PPLL output as the external
      compression of the head was increased indicates that the PPLL output represents
      substantial skull movement associated with altered ICP. In conclusion, the
      ultrasound device has sufficient sensitivity to detect transcranial pulsations
      which occur in association with the cardiac cycle. Our technique makes it
      possible to analyze ICP waveforms noninvasively and will be helpful for
      understanding intracranial compliance and cerebrovascular circulation.

PMID- 9779148
TI  - Non-invasive measurement of intracranial pressure in neonates and infants:
      experience with the Rotterdam teletransducer.
AB  - On the basis of an experience of more than 400 recordings, we demonstrate the
      usefulness of the anterior fontanelle pressure monitoring (AFP) in several
      clinical conditions. Main indications for AFP monitoring are the evaluation and
      the differential diagnosis of neonatal encephalopathy and the assessment of
      infants with enlarged ventricular spaces, ventriculo-peritoneal derivation or
      increased head growth rate. Further technical progress is needed to permit AFP
      recordings in infants with small anterior fontanelle and to reduce the time
      necessary for the AFP measurement and interpretation procedure. We conclude that
      it is technically possible and clinically helpful to obtain accurate information
      about ICP and changes in cerebral compliance in a wide range of clinical
      conditions without the use of invasive techniques.

PMID- 9779149
TI  - Continuous monitoring of cerebrovascular pressure-reactivity in head injury.
AB  - OBJECTIVE: Cerebrovascular vasomotor reactivity reflects changes in smooth muscle
      tone in the arterial wall in response to changes in transmural pressure or
      concentration of carbon dioxide in blood. We have investigated whether slow waves
      in ABP and ICP may be used to derive an index which reflects reactivity of
      vessels to changes in arterial blood pressure. METHODS: A method for the
      continuous monitoring of the association between slow spontaneous waves in ICP
      and AP has been adopted in a group of 98 head injured patients. ABP, ICP and
      transcranial Doppler blood flow velocity (FV) in the middle cerebral artery was
      recorded daily (20 to 120 minutes time periods). A Pressure-Reactivity Index
      (PRx) was calculated as a moving correlation coefficient between 40 consecutive
      samples of values for ICP and ABP averaged over 5 seconds. A moving correlation
      coefficient between spontaneous fluctuations of mean FV and CPP (Mx), which was
      previously reported to describe cerebral blood flow autoregulation, was also
      calculated. In an additional 25 patients, PRx was calculated and recorded
      continuously along with mean ICP, ABP and parameters describing ICP waveform.
      RESULTS: A positive PRx correlated with high ICP (r = 0.366; p < 0.001), low
      admission GCS (r = 0.29; p < 0.01), and poor outcome at 6 months after injury (r
      = 0.48; p < 0.00001). During the first two days following injury, PRx was
      positive (p < 0.05) in patients with unfavourable outcome. The correlation
      between PRx and Mx (r = 0.63) was highly significant (p < 0.000001). Continuous
      recordings demonstrated that PRx was able to indicate individual thresholds of
      vascular reactivity for CPP, ICP, and ventilation parameters. CONCLUSION:
      Computer analysis of slow waves in ABP and ICP is able to provide a continuous
      index of cerebrovascular reactivity to changes in arterial pressure, which is of
      prognostic significance.

PMID- 9779150
TI  - Real-time multiparametric monitoring of the injured human cerebral cortex--a new
      approach.
AB  - Intracranial pressure (ICP) is currently the main parameter monitored following
      severe head injury or during the post operative period in neurosurgical patients.
      The normal cerebral cortex depends upon a continuous supply of O2, and direct
      coupling exists between adequate cerebral blood flow (O2 supply) and ion
      homeostasis as well as electrical activities. We have developed a new "Brain
      Function Analyzer-BFA" which enabled monitoring of the following parameters
      continuously in real time from the surface of the cortex: ICP; tissue blood flow
      & volume; intramitochondrial NADH redox state; DC steady potential;
      electrocorticography; tissue temperature. The probes were assembled in a Brain
      Function Multiprobe (BFM) which was connected to the brain via the burr hole
      procedure used for ICP monitoring. Measurements were performed in 18 comatose
      patients after severe head injury (GCS < or = 8) who were monitored in the ICU
      for 48-72 hours. The basic concept of the multiparametric monitoring approach was
      proven to be practical in neurosurgical patients. Clear correlations were
      recorded between hemodynamic, metabolic, ionic and electrical activities under
      various treatments administered to the patients or after pathological events.
      Responses similar to cortical spreading depression and ischemic depolarization
      were recorded from a severely head injured patient.

PMID- 9779151
TI  - Continuous intracranial multimodality monitoring comparing local cerebral blood
      flow, cerebral perfusion pressure, and microvascular resistance.
AB  - Maintaining cerebral perfusion pressure (CPP) above 70 mmHg is currently a
      mainstay of neurosurgical critical care. Shalmon, et al. recently showed poor
      correlation between CPP and regional cerebral blood flow (CBF) [1]. To study the
      relationship between CPP and CBF, at a microvascular level, we retrospectively
      analyzed multimodality digital data from 12 neurosurgical critical care patients
      in whom a combined intracranial pressure (ICP)--laser Doppler flowmetry (LDF)
      probe (Camino, San Diego) had been placed. Over the entire interval of continuous
      monitoring for all patients, 97% of local CBF data was at ischemic levels below a
      CPP of 70 mmHg. For CPP above 70 mmHg, local CBF data had considerable dispersion
      ranging from ischemic (71%), to normal (19%), and hyperemic (10%) levels.
      Elevated jugular bulb oxyhemoglobin saturation levels (SjO2) complemented
      intervals of hyperemia. Autoregulation was impaired or absent in all monitored
      patients. We conclude that with disrupted autoregulation, CPP above 70 mmHg does
      not necessarily insure adequate levels of cerebral perfusion. Restoration and
      maintenance of adequate cerebral perfusion should be performed under the guidance
      of direct CBF monitoring.

PMID- 9779152
TI  - Significance of multimodal cerebral monitoring under moderate therapeutic
      hypothermia for severe head injury.
AB  - The therapeutic significance of moderate hypothermia and cerebral monitorings was
      assessed in the 10 patients with severe head injury. Cooling was begun as soon as
      possible after admission, using water blankets under general anesthesia. Jugular
      venous or tympanic temperature of patients was maintained at 32 degrees C for 3
      to 5 days, then rewarming at the rate of 1 degree C a day was started. The
      intracranial pressure was controllable less than 20 mmHg under hypothermia.
      Moderate hypothermia reduced the jugular venous lactate (33.5%) as well as the
      cerebral blood flow velocity at M1 portion of middle cerebral artery (CBFV-M1)
      measured by transcranial Doppler (7.2%), while increase of the jugular venous
      oxygen saturation (SjO2) (17.9%) was observed in a majority of the patients. Our
      results demonstrated that moderate therapeutic hypothermia significantly reduced
      cerebral circulation and metabolism. Measurement of SjO2 and CBFV-M1 seems to be
      useful for estimation of cerebral circulation and metabolism in therapeutic
      hypothermia.

PMID- 9779153
TI  - Brain-stem auditory evoked potential monitoring in experimental diffuse brain
      injury.
AB  - The time course of brain-stem auditory evoked potential (BAEP) changes was
      investigated using an impact-acceleration trauma model in 23 spontaneously
      breathing rats. Intracranial pressure (ICP), arterial blood pressure and
      respiratory rate were monitored. The experiments were terminated at four hours
      after trauma. No significant changes in intracranial pressure (ICP) occurred
      following the impact. After a short increase, blood pressure returned to baseline
      values within 5 min. Transient apnea was not followed by prolonged respiratory
      depression. Diffuse closed head injury (CHI) did not result in general,
      unidirectional changes of peak latencies or amplitudes of auditory evoked
      responses. Most BAEP changes developed slowly reaching a maximum at 1 to 4 hours
      after the injury. In the absence of ICP changes, this pattern reflects secondary
      ischemia in sensitive brain-stem areas rather than direct traumatic lesions or
      hypoxia due to respiratory depression.

PMID- 9779154
TI  - Complications and safety associated with ICP monitoring: a study of 542 patients.
AB  - In our institution ICP was monitored in patients with GCS < or = 8 and abnormal
      CT scan: 362 severely head injured and 180 subarachnoid hemorrhage. Mean duration
      of monitoring was 103.6 hours (SD 74.96). Among 542 patients, 440 showed at least
      one episode of ICP above the threshold of 20 mm Hg. Among 362 head injured
      patients only 71 (19.3%) had an ICP lower than 20 mm Hg. In the remaining 289
      (81.7%) at least one episode > or = 20 mm Hg was measured. In 13 cases (2.2%) a
      ventricular infection has been diagnosed. In 1 case an intraparenchimal
      hemorrhage related to the presence of the catheter was detected. Elevated risk of
      HICP and low incidence of complications have been shown in this series.

PMID- 9779155
TI  - Morphological and hemodynamic evaluations by means of transcranial power Doppler
      imaging in patients with severe head injury.
AB  - The following conditions of 17 patients with severe head injury (ages 9-76; mean
      37:12 focal and 5 diffuse injuries) were evaluated during acute phase (1-14 days
      after injury, mean 5) by transcranial power Doppler imaging (PDI), a new color
      Doppler ultrasound technique: a) morphological changes via temporal window, b)
      hemodynamic changes in major intracranial/cervical arteries based on measured
      angle-corrected time-averaged mean (TAM)/ peak velocities and vessel diameter
      (Va), and calculated pulsatility indices (PI), vessel area (Va), and flow volume
      (Vf = TAM x Va). a) 1) Major trunks of intracranial vessels and circle of Willis
      and pathological changes in frontal/temporal lobes and midbrain were finely
      visualized. 2) Contusional hemorrhage and cerebral contusion demonstrated
      irregular hyper- and hypo-echoic lesions, respectively. 3) Delayed epidural
      hematoma showed a hyper-echoic band. b) 1) Decreased velocities, significant PI
      increase, and Va increase tendency were observed in intracranial arteries. 2)
      Increased velocities with Vf increase but no Va decrease indicated hyperemia
      rather than vasospasm. 3) Va in the intracranial vessels, however, tended to
      increase PDI appears useful in evaluating real-time and simultaneous
      morphological and hemodynamic information in pathogenesis and neurointensive care
      of patients with severe head injury.

PMID- 9779156
TI  - The effect of experimental spinal cord edema on the spinal evoked potential.
AB  - Experimental spinal cord edema was successfully produced in the cat intumescentia
      cervicalis by the infusion method of Marmarou. The water content around the
      infusion site significantly increased to 75.9% from the normal value of 69.8% of
      white matter in the lateral column, with the infusion of 20 microliters of
      autoserum. The edema was observed for a length of ca.20 mm, spreading mainly
      longitudinally in the lateral column. The spinal evoked potential was measured
      four times on the course of infusion and the N1 peak latency at the end of
      infusion did not show any significant difference compared to the value before
      infusion. This model may contribute to basic understanding of pathophysiology of
      spinal cord edema by changing the nature and the volume of infusate, and the
      location of infusion, according to the experimental purpose.

PMID- 9779157
TI  - Blood brain barrier permeability and acute inflammation in two models of
      traumatic brain injury in the immature rat: a preliminary report.
AB  - We sought to investigate the course and magnitude of blood brain barrier (BBB)
      permeability following focal and diffuse traumatic brain injury (TBI) in immature
      rats and examine the time course of markers of acute inflammation (neutrophil
      accumulation and E-selectin [E-sel] expression) following these two types of
      injury. We measured BBB permeability using i.v. injection Evans Blue (EB) and the
      extent of inflammation using immunohistochemical techniques identifying
      neutrophils (monoclonal antibody RP-3) and the endothelial adhesion molecule, E
      selectin. Male Sprague-Dawley immature (17 day-old) rats (30-45 g, n = 80) were
      subjected to a controlled cortical impact (CCI: 2 mm, 4 m/s), a closed head
      diffuse injury (DI: 150 g/2m) or a corresponding sham procedure (with or without
      craniotomy). EB was injected i.v. at 30 min before sacrifice, which occurred at 1
      h, 4 h, or 24 h after injury. BBB permeability was observed in both the CCI and
      DI rats at 1 h after injury which largely resolved by 24 h. In the CCI, EB
      extravasation was seen within and around the contusion. In DI, diffuse BBB
      permeability was seen. DI was not associated with acute inflammation since there
      was neither neutrophil accumulation nor E-selectin expression. The CCI rats
      though had 5.1 +/- 2.2 neutrophils/hpf and 3.0 +/- 0.4 endothelial cells/hpf
      expressing E-selectin (mean +/- SEM) (both p < 0.05 vs sham and DI). These data
      suggest that BBB breakdown occurs in the immature rat after both focal and
      diffuse TBI. This early BBB permeability was not associated with acute
      inflammation in DI but was in CCI. These data also suggest that contusion is a
      key factor in the development of a traditional acute inflammatory response after
      TBI in the immature rat.

PMID- 9779158
TI  - Prospective analysis of patient management in severe head injury.
AB  - Severe head injury with and without peripheral trauma is the most frequent cause
      of death and of severe disability up to 45 years. Outcome is determined by two
      major factors, the extent and nature of the irreversible primary brain damage,
      and the evolving secondary sequelae, which contrary to the former are responsive
      in principle to therapeutic intervention. An improvement of outcome from severe
      head injury can be expected only from an increased efficiency of the measures to
      prevent secondary brain damage. A research consortium "Neurotrauma" was formed by
      the University of Munich in collaboration with almost all city hospitals in
      Munich, Augsburg, Murnau, Ingolstadt, Vogtareuth and Southern Bavaria, providing
      care for neurotrauma patients. These hospitals together with the associated
      organizations carry out a system analysis on the management, logistics,
      organization, patient referral, etc. In severe head injury. Data acquisition is
      e.g. also concerned with outcome-relevant time periods of emergency care measures
      in the pre-clinical phase until hospital admission, conclusion of diagnostic
      procedure, and of the initial clinical care. Current results and experiences with
      establishment of this comprehensive research organization are presented, where no
      less than 31 hospitals. Institutions and organizations, and a study group of more
      than 40 physicians, students and statisticians are collaborating. Emerging data
      appear to be suitable to further improve pertinent aspects of the patient
      management as a basis to lower the incidence of secondary brain damage from
      severe head injury.

PMID- 9779159
TI  - Effects of cerebral perfusion pressure on brain tissue PO2 in patients with
      severe head injury.
AB  - Ischemia causes secondary brain damage after severe head injury (SHI). Cerebral
      perfusion is commonly estimated by monitoring CPP, but the adequacy of cerebral
      oxygenation requires further measurements, such as jugular oxygen saturation or,
      more recently, PtiO2 monitoring. In 7 patients with severe head injury, ICP, MAP,
      CPP, SjO2 and PtiO2 were monitored for a mean time of 9.0 +/- 2.2 days. Most of
      the data were in a "normal" range. Focusing on values under the thresholds of 60
      mm Hg for CPP and 20 mm Hg for PtiO2, we found a relationship between CPP and
      PtiO2. Looking at the PtiO2 time-course, we observed a quite constant increasing
      trend during the first 48 hours of monitoring, then the values remained
      relatively constant within a normal range. Our data show that decreases of PtiO2
      are not uncommon after severe head injury and therefore it seems that monitoring
      of PtiO2 in SHI may be useful in order to minimize secondary insults.

PMID- 9779160
TI  - Neuroprotective properties of aptiganel HCL (Cerestat) following controlled
      cortical impact injury.
AB  - Recent studies revealed a neuroprotective effect of the non-competitive NMDA
      receptor antagonist Aptiganel HCL (Cerestat CNS 1102) in focal cerebral ischemia.
      This study investigates the influence of Cerestat on contusion volume, post
      traumatic brain edema and intracranial pressure (ICP) following Controlled
      Cortical Impact Injury (CCII). In rats (n = 54) CCII was applied to the left
      hemisphere using a pneumatic impactor. Cerestat (2 mg/kg i.v.) or vehicle was
      injected 15 min after injury animals were sacrificed 24 hours later. Contusion
      volume was measured planimetrically (n = 18). Hemispheric swelling and water
      content were determined gravimetrically (n = 20). ICP, mean arterial blood
      pressure (MABP) and cerebral perfusion pressure (CPP) were monitored for 30 min
      before sacrifice (n = 16). Cerestat reduced contusion volume from 77.3 +/- 5.8
      mm3 to 66.8 +/- 3.9 mm3 (p < 0.05). Hemispheric swelling was also diminished from
      11.1 +/- 0.8% to 8.2 +/- 1.4% as soon was water content (Cerestat 82.30 +/- 0.18%
      vs. control: 82.78 +/- 0.12%, p < 0.05). ICP was decreased by treatment from 31.7
      +/- 3.5 mm Hg to 26.3 +/- 2.2 mm Hg and CPP was significantly improved (82.1 +/-
      4.4 mm Hg vs 57.7 +/- 4.8 mm Hg; p < 0.05) 24 hours after injury. Cerestat
      administration was associated with decrease contusion volume, less hemispheric
      swelling, a lower ICP and increased CPP.

PMID- 9779161
TI  - Relationship of neuron specific enolase and protein S-100 concentrations in
      systemic and jugular venous serum to injury severity and outcome after traumatic
      brain injury.
AB  - Neuron specific enolase (NSE) and protein S-100 have previously been described as
      markers of brain injury. We aimed to discover whether concentrations of either
      were raised in arterial and jugular venous serum after traumatic brain injury,
      and whether serum profiles were related to injury severity and neurological
      outcome. We recruited 22 patients with a traumatic brain injury who were admitted
      to the intensive care unit. Paired arterial and jugular venous blood samples were
      taken on admission, and at 24, 48 and 96 hrs after injury. Samples were analysed
      for NSE and S-100 by RIA. Concentrations of both NSE and S-100 were increased
      above controls--mean NSE concentration was highest on admission, whilst mean S
      100 peaked at 24 hours after injury. There was a small, but significant
      difference between jugular venous and arterial concentrations of S-100 (p =
      0.022). High NSE and S-100 concentrations were significantly related to poor
      neurological outcome (p = 0.004 and p < 0.001 respectively). Both serum NSE and S
      100 may be of some value in helping to predict outcome after a traumatic brain
      injury.

PMID- 9779162
TI  - Antioxidant, OPC-14117, attenuates edema formation, and subsequent tissue damage
      following cortical contusion in rats.
AB  - Oxygen free radicals contribute to various kinds of tissue injury processes
      within the central nervous system. It has been suggested that inhibition of free
      radical formation has the potential to attenuate secondary neural tissue damage
      involving ischemia or trauma, and antioxidant therapy may offer a promising
      approach. In the present study, employing a cortical contusion model in the rat,
      contusion-induced neural damage, was evaluated by investigating edema formation,
      behavioral activities and histological changes. The effects of the superoxide
      radical scavenger, OPC-14117, were also tested to determine how free radicals may
      contribute to such neural damage. The results demonstrated that cerebral
      contusion induces a progressive decrease in tissue specific gravity representing
      edema formation, and behavioral deficits in the Morris water maze test and
      habituation of exploratory activity. Histological examinations revealed necrotic
      cavity formation in the cortex and selective neuronal death of the hippocampal
      CA3 region. These changes were significantly attenuated by OPC-14117, which was
      administered as a single dose immediately following trauma induction. The above
      results indicate that oxygen free radicals are involved in contusion-induced
      edema formation, subsequent tissue damage and cognitive deficits. The superoxide
      radical scavenger, OPC-14117, has a powerful therapeutic potential for preventing
      secondary cell damage following traumatic brain injury.

PMID- 9779163
TI  - Failure of cerebral autoregulation in an experimental diffuse brain injury model.
AB  - The normal cerebral circulation has the ability to maintain a stable cerebral
      blood flow over a wide range of cerebral perfusion pressures and this is known as
      cerebral autoregulation. Autoregulation may be impaired in the injured brain.
      Closed head injury was induced in 28 Sprague-Dawley rats weighing 400-450 g. Four
      groups were studied: control and groups, head injured by weight drop from one
      meter height using 350 g, 400 g and 450 g respectively. CBF was monitored using
      laser-Doppler flowmetry along with monitoring of ICP and arterial blood pressure.
      If the correlation coefficient between CBF and CPP was > 0.85 and CPP was within
      normal range, loss of autoregulation was hypothesized. Loss of autoregulation was
      seen in all groups of injured rats during first four hours. A statistically
      significant difference (p = 0.041) was seen in the trequency of loss of
      autoregulation between injured and control animals. No loss of autoregulation was
      observed in the control group. In conclusion CBF and CPP provide information
      about loss of autoregulation in diffuse brain injury. Decrease in CBF and
      increase of ICP is observed as a result of loss of cerebral autoregulation.
      Knowledge of loss of autoregulation could help in the management of head injured
      patients.

PMID- 9779165
TI  - Moderate hypothermia and brain temperature in patients with severe middle
      cerebral artery infarction.
AB  - Elevated temperature is known to facilitate neuronal injury after ischemia. After
      head injury a gradient between temperature and body temperature of up to 3
      degrees C higher in the brain has been reported. Hypothermia may limit some of
      the deleterious metabolic consequences of such increased temperature. In 20
      patients who had suffered severe ischemic stroke in the middle cerebral artery
      (MCA) territory, intracerebral temperature combined with ICP monitoring was
      recorded using two different thermocouples, with epidural, and parenchymatous
      measurements. Mild hypothermia was induced using cooling blankets. Patients were
      kept at 33 degrees C core temperature for 48 to 72 hours. In all patients brain
      temperature exceeded body-core temperature by at least up to 1 degree C (range
      1.0-2.1 degrees C). Systemic cooling was effective and sustained hypothermic (33
      34 degrees C) brain temperatures. With mild hypothermia critically elevated ICP
      values could be controlled. 12 patients survived the hemispheric stroke with a
      mean Barthel index of 70. Severe side effects of hypothermia were not detected.
      After MCA stroke, human intracerebral temperature is higher than central body
      core temperature. Mild hypothermia in the treatment of severe cerebral ischemia
      using cooling blankets is safe and does not lead to severe side effects. Mild
      hypothermia can help to control critically elevated ICP values in severe space
      occupying stroke and may improve clinical outcome in these patients.

PMID- 9779164
TI  - Early cerebral blood volume after severe traumatic brain injury in patients with
      early cerebral ischemia.
AB  - Recent early cerebral blood flow (CBF) studies on severe head injury have
      revealed ischemia in a substantial number of patients with a variety of CT
      diagnoses. However, the underlying derangements causing this early ischemia are
      unknown, but cerebral blood volume (CBV) measurements might offer some insight
      into this pathology. Therefore, acute CBF and CBV measurements were performed in
      51 adult severely head injured patients within 24 hours after injury. For this
      purpose the stable Xenon-CT procedure was used for assessment of CBF, and a
      dynamic CT imaging technique was used for determining CBV. All ischemic patients
      were found among 35 subjects studied within 4 hours after injury (31%). Based on
      the occurrence of regional ischemia seven patients with varying anatomical
      lesions on CT were selected for comparison between CBF and CBV in ischemic and
      non-ischemic areas. Both CBF (p < 0.02) and CBV (p < 0.02) exhibited
      significantly lower values in the ischemic zones. Ten patients showing a subdural
      hematoma (SDH) were studied preceding surgery and seven were ischemic in at least
      one lobe or brainstem. Ipsilateral CBF was lower than CBF in the contralateral
      side (p < 0.1). CBV at the ipsilateral side was significantly reduced compared to
      the contralateral side (p < 0.05). Follow-up studies were performed in three
      ischemic patients and in one borderline ischemic patient immediately after
      removal of SDH showing a striking increase in both CBF and CBV. In the remaining
      26 subjects follow-up studies were obtained between day 2 and day 8 and all
      patients showed CBF values within the normal range. These data evidently support
      the suggestion that compromise of the microvasculature is the cause of early
      ischemia, rather than vasospasm of the larger conductance vessels. This has
      implications for acute post-traumatic therapeutical strategies and management of
      the severely head injured patient and may lead to testing of new drugs that are
      effective in interfering with processes causing this ischemia.

PMID- 9779166
TI  - Traumatic brain injury in the developing rat pup: studies of ICP, PVI and
      neurological response.
AB  - Diffuse brain swelling is a common complication in young victims of a seven head
      injury but, there is a lack of data on relevant models of injury. We produced
      diffuse brain injury in 21 day old Lewis rat pups (N = 33) by modifying a
      recently established weight-drop-model. The trauma threshold, neurological
      response, histological changes, intracranial pressure (ICP), and arterial blood
      pressure (ABP) were determined. In addition, the pressure-volume-index (PVI) was
      measured 15 min before, 2 min, and 1 h after brain injury. In the 1 m/100 g group
      4 of 5 rats died, whereas in the 0.5 m/100 g only 4 of 28 died. The PVI increased
      at 2 min after traumatic brain injury (TBI) but ICP was unchanged, except for a
      minor increase immediately after injury. Histological studies revealed diffuse
      neuronal death, predominantly involving the cortex and hippocampus. The results
      of the present study indicate that determination of ICP in the developing rat pup
      during and after diffuse brain injury is possible. A 0.5 m/100 g weight-drop
      trauma results in a morphologically severe injury but with low mortality. The
      increase in PVI can be attributed to a decrease of cerebral perfusion pressure
      (CPP) after injury. However, the absence of a further increase of ICP after
      injury in the developing rat indicates that this may not be a primary consequence
      of injury in paediatric patients.

PMID- 9779167
TI  - Efficiency of the Glasgow Outcome Scale (GOS)-Score for the long-term follow-up
      after severe brain injuries.
AB  - The Glasgow Outcome Scale (GOS)-Score is the most widely used instrument for
      measuring outcome in head injury research. Its reliability is seen controversial
      because of its simplicity. The study analyzes the correlation between the levels
      3 to 5 of recovery to medical data, psychology and quality of life (QOL) 4 to 8
      years after the accident. 34 patients, suffered from a severe brain injury (BI) 4
      to 8 years ago, were reexamined by a psychological test battery and by evaluating
      of QOL (using self developed items for private and social activity). Test results
      and GOS-Score additionally were correlated to data from the phase of intensive
      care. Patients, still alive 4 to 8 years after injury, ranged mainly between the
      GOS-Scores 3 to 5 of recovery. Consequently, other scores (like Ranchos los
      Amigos, Barthel Index, GOAT) failed in measuring the outcome after such a long
      time. Different parameters from the phase of intensive care correlate
      significantly with the patients GOS-Score: coma length, isolated brain injury
      versus additional extracranial injury, compression of the basal cisternes on the
      initial CCT. Different psychological test results and the patients quality of
      life correlate significantly with the GOS-Scores from 3-5. These correlations
      could be shown in xy and yx-direction by different mathematical models. It is
      concluded, that GOS-levels 3-5 of recovery correlate to the essential medical
      data from the initial phase after the accident and to a detailed psychological
      evaluation years after injury.

PMID- 9779168
TI  - Effects of lecithinized SOD on sequential change in SOD activity after cerebral
      contusion in rats.
AB  - To analyze the effect of lecithinized superoxide dismutase (SOD) on superoxide
      accumulation after traumatic brain injury (TBI) in rats, we studied the SOD
      activity by NBT-reducing method and the expression of Cu,Zn-SOD mRNA by Northern
      blot analysis. As determined by the specific gravity method, the administration
      of lecithinized SOD decreased brain edema in the periphery of the lesion at 6 hr
      after contusion. SOD activity, without lecithinized SOD administration, increased
      at the peripheral portion at 30 min after contusion, but decreased to normal
      level at 6 hr after TBI. By administration of lecithinized SOD, the increase of
      SOD activity was preserved until 6 hr after TBI. The expression of Cu,Zn-SOD mRNA
      increased in the core lesion, peripheral portion, and contralateral hemisphere
      until 6 hr after TBI, then was suppressed in all three areas by lecithinized SOD.
      These results support the hypothesis that superoxide anions may play an important
      role in the development of brain edema after TBI, and that leciyhinized SOD
      appears to prevent brain edema through a protective effect against superoxide
      anions.

PMID- 9779169
TI  - CSF antibiotic prophylaxis for neurosurgical patients with ventriculostomy: a
      randomised study.
AB  - The value of prophylactic antibiotics for patients with ventricular catheter for
      monitoring and CSF drainage is uncertain. 228 patients were randomised to receive
      perioperative antibiotics only (Unasyn, Group I) or prolonged antibiotics for the
      presence of the ventricular catheter (Unasyn and Aztreonam, Group II). The
      incidence of intracranial and extracranial infection was documented
      prospectively. Group II patients had a significantly reduced incidence of CSF
      infection [3/115 (3%) vs 12/113 (11%), p = 0.01] and extracranial infections
      [23/115 (20%) vs 48/113 (42%), p = 0.002]. CSF pathogens in Group II patients
      were MRSA and Candida, whereas in Group I, Staphylococci, E coli and Klebsiella.
      Although prolonged antibiotic prophylaxis significantly reduced the incidence of
      serious CSF infection as well as extracranial infections, this policy did select
      resistant or opportunistic pathogens such as Candida and MRSA.

PMID- 9779170
TI  - The effect of human corticotrophin releasing factor on the formation of post
      traumatic cerebral edema.
AB  - Controlled cortical impact is a well validated model of cortical contusion which
      is known to produce cerebral edema. Corticotrophin Releasing Factor (CRF) is a
      hypothalamic neuropeptide, which is known to inhibit transendothelial leakage of
      plasma derived fluid and tissue edema in response to injury. The aim of this
      study was to determine cerebral edema after controlled cortical impact and then
      compare the effect of high and low doses of CRF. We evaluated the effect of CRF
      in rats divided into groups of sham, trauma alone, and trauma treated with CRF at
      50 micrograms/kg and 100 micrograms/kg. Animals were sacrificed at 24 hours and
      water content was determined. We found that CRF was effective in reducing
      cerebral edema associated with cortical contusion and propose that the action of
      CRF obviated barrier leakage.

PMID- 9779171
TI  - Monitoring of brain tissue PO2 in traumatic brain injury: effect of cerebral
      hypoxia on outcome.
AB  - This study investigates the effect of hypoxic brain tissue PO2 on outcome, and
      examines the incidence of possible causes for cerebral hypoxia. We studied 35
      patients with severe head injury (GCS < or = 8). Age was 33.2 (+/- 11.3) years.
      Total time of monitoring of PtiO2, intracranial pressure (ICP), cerebral
      perfusion pressure (CPP), and endtidal PCO2 (ETCO2) was 119.3 (+/- 65.7) hours.
      Data were continuously recorded by a computer system. Outcome was assessed at
      discharge and after 6 months post injury. 56% of the patients with more than 300
      minutes of PtiO2 < 10 mm Hg died, 22% had an unfavourable outcome, 22% had a
      favourable outcome. Cerebral hypoxia was associated with intracranial
      hypertension (ICP > 20 mm Hg) in 11.5 (+/- 15.1)%. CPP was compromised below 60
      mm Hg in 16.8 (+/- 23.4)%. Hypocarbia (ETCO2 < 28 mm Hg) was present in 48.0% of
      the time of PtiO2 < 10 mm Hg. No obvious cause for cerebral hypoxia was found in
      45% of the data. These result underscore the association of cerebral hypoxia with
      poor neurological outcome and stress the meaning of monitoring of PtiO2 as an
      independent parameter in patients following TBI.

PMID- 9779172
TI  - Bilateral monitoring of CBF and tissue oxygen pressure in the penumbra of a focal
      mass lesion in rats.
AB  - The continuous monitoring of cerebral microcirculation is aimed at preventing
      secondary ischemic brain damage subsequent to severe head injury. Interrelations
      between bilateral changes of cortical Laser Doppler Flowmetry (LDF) and
      intraparenchymal, subcortical p(ti)O2 values were continuously monitored in the
      forebrain of rodents. A trauma group of 8 animals received an unilateral, focal
      parietal mass lesion by an expanding epidural balloon. 10 animals served as a
      sham group. In the sham-operated group the drift of median LDF values was 10.8%
      in the left and 9.6% in the right hemisphere. The absolute median p(ti)O2 showed
      values of 31.2 mm Hg (27.9-34.9) in the left and 30.1 mm Hg (27.5-31.7) in the
      right hemisphere. During maximum brain compression median LDF values decreased
      ipsilateral to 18.6% (13.3-24.4%) and contralateral to 23.4% (17.1-56.6%) of the
      baseline values. P(ti)O2 decreased ipsilateral to absolute values of 4.6 mm Hg
      (3.2-6.7 mm Hg) and contralateral to values of 7.1 mm Hg (6.1-8.5 mm Hg). After
      balloon deflation cortical LDF was restored much faster but did not reach
      baseline values [ipsilateral 55.2% (42.6-67.8%); contralateral 67% (53.4-82%) of
      baseline values]. The p(ti)O2 values reached ipsilateral 77.4% (72.0-93.3%) and
      contralateral 88.8% (86.0-97.4%) of baseline values. Both parameters showed a
      significant correlation (r = 0.57; p < 0.02). P(ti)O2 measurements supplement on
      line cortical CBF monitoring and by far outscore discontinuous alternative
      measurement techniques in detecting hemodynamically relevant events. The small
      spatial resolution of the p(ti)O2 probes, however, which in the small animal
      model may be of negligible influence, does raise the question whether the values
      gained offer a general overview of the microcirculatory situation.

PMID- 9779173
TI  - High cerebral perfusion pressure improves low values of local brain tissue O2
      tension (PtiO2) in focal lesions.
AB  - Arterial hypertension is widely applied to improve regional cerebral blood flow
      (rCBF). We measured local brain tissue O2 pressure (PtiO2) in low density lesions
      at computerized tomography (CT) of the head before and after manipulation of mean
      arterial pressure (MAP) in order to increase cerebral perfusion pressure (CPP).
      Nine patients, 7 subarachnoid hemorrhage (SAH), 1 severe head injury, 1
      meningeoma, were included in our study. A flexible polarographic microcatheter
      for PtiO2 measurement was placed at the border of the low density area found at
      CT. PtiO2 was continuously measured for 615 hours. Hypoperfusion in low density
      areas was detected by perfusional single photon emission computed tomography
      (SPECT). We recorded 22 episodes of induced or spontaneous increase of MAP.
      Initial PtiO2 regularly improved after the CPP increase (r2 0.74 in induced
      episodes). Low PtiO2 showed a greater percent increase for unitary changes of CPP
      than normal-high PtiO2. Baseline PtiO2 below 20 mm Hg was associated with normal
      CPPs; 5 readings of PtiO2 below 20 mm Hg normalized when a higher CPP was
      obtained. Our results show that in ischemic areas PtiO2 is dependent on CPP
      suggesting both a derangement of pressure autoregulation and high regional
      cerebrovascular resistences (CVRs). Low PtiO2 was associated with normal CPP,
      thus indicating that CPP could be an inadequate estimate of rCBF in focal
      ischemic areas. Arterial hypertension, capable of increasing CPP above normal
      values, appeared useful in normalizing tissue oxygenation in ischemic areas.

PMID- 9779174
TI  - Determination of the ischemic threshold for brain oxygen tension.
AB  - Measuring brain tissue oxygenation is now possible due to major advances in the
      technical development of Clark-electrodes and fiberoptic systems. However, to
      make this technique clinically useful for both nurses and medical staff, the
      ischemic threshold for brain tissue oxygen tension (brain pO2) must be
      determined. Three end points were used for determination of the critical brain
      pO2 value. 1) Infarct determination after permanent middle cerebral artery
      occlusion in a feline model. 2) Threshold analysis using the schemic threshold
      for cerebral blood flow (CBF) as a "gold standard" in severely head injury
      patients. 3) Outcome analysis in severely head injured patients. Brain pO2
      dropped to 19 +/- 6 mm Hg and 23 +/- 6, 4 to 5 hours after MCA occlusion in the
      cat (n = 12). In severely head injured patients, a brain pO2 < or = 19 mm Hg was
      correlated with poor outcome (n = 24). The ischemic threshold for (r)CBF of 18
      ml/100 g/min corresponded to a brain pO2 of 22 mm Hg, in the same patients. By
      using the above mentioned end points as a reference, we found the critical value
      for brain pO2 to be in between 19 and 23 mm Hg. Clearly, the difference between
      our threshold value and the lower critical brain pO2 level found by other groups
      using the Licox system, needs to be clarified in a comparison study before a
      uniform threshold for brain pO2 can be determined.

PMID- 9779175
TI  - Brain ischemia detected by tissue-PO2 measurement and the lactate-oxygen index in
      head injury.
AB  - The aim of the study was to find out whether there is a correlation between the
      tissue-pO2 (ti-pO2) measurement and the lactate-oxygen index (mLOI). Both methods
      are to be considered as methods to detect brain ischemia. We studied 7 patients
      after severe head injury (GCS < 8) with a jugular bulb catheter and a tissue pO2
      probe. Possible ischemia was defined with ti-pO2 below 10 mm Hg and mLOI above
      0.08. 67 pairs of ti-pO2 and corresponding mLOI were found. In 5 cases out of the
      7 cases with a ti-pO2 below 10 we found a pathological mLOI above 0.08. In 11
      cases with pathological mLOI values, however, we found only 6 cases of decreased
      ti-pO2. The absolute values did not correlate. The sensitivity to predict normal
      values is above 85% with both methods. The specifity to predict ischemia is low
      (< 72%). The reason is the fact, that ti-pO2 is a local method in contrast to the
      mLOI values. In cases of diffuse brain injury without major contusions there
      should be a correlation between ti-pO2 and the mLOI.

PMID- 9779176
TI  - Bifrontal measurements of brain tissue-PO2 in comatose patients.
AB  - The purpose of this study was to compare brain tissue-PO2 (PtiO2) in lesioned vs.
      non-lesioned brain tissue. PtiO2 was monitored bifrontally with a "Clark"-type
      microcatheter in patients following severe head injury (n = 6) and subarachnoid
      hemorrhage (SAH) (n = 1) from day 2 to day 12 posttrauma/post SAH. Mean arterial
      blood pressure, intracranial pressure (ICP), cerebral perfusion pressure and end
      tidal CO2 were monitored. Data were stored and analyzed by a multimodal cerebral
      monitoring system. The CT of five patients was classified as "diffuse injury" and
      of one patients as "evacuated mass lesion". The patient with SAH (Hunt and Hess
      IV) had a concomitant intracerebral hematoma which was removed. In all cases, one
      catheter was placed close to the lesion, while the other was situated in an area
      with no visible pathology. For analysis, bifrontal PtiO2 data were taken from
      both on-line monitoring and O2 reactivity tests (FiO2 1.0 for 10 min). Two
      different patterns were identified: periods of concordance (22% of recordings)
      and periods in which PtiO2 was lower in lesioned cerebral white matter (78%) but
      always running parallel. In the latter case, O2-reactivity response was markedly
      reduced on the lesioned side. Our findings demonstrate a decreased PtiO2 and a
      reduced O2 reactivity in contused or infarcted brain tissue. Future studies have
      to clarify which PtiO2 is more important to be used as a guide for therapy.

PMID- 9779178
TI  - Effects of injury and therapy on brain parenchyma pO2, pCO2, pH and ICP following
      severe closed head injury.
AB  - Simultaneous monitoring of brain parenchyma pO2, pCO2, and pH (PbO2, PbCO2 and
      pHb) has been tested in ICU environments using fiber optic sensors incorporated
      in probes 0.5 mm in diameter. An Institutionally approved protocol was used to
      test the concept and technology for monitoring PbO2, PbCO2 and pHb, and to
      observe the effects of injury and therapy interventions on each of the variables
      monitored, including ICP, the clinical standard. ICP and fiber optic pO2, pCO2
      and pH probes were placed in 10 SCHI patients at bedside in the ICU using sterile
      technique. The probes remained in place for the duration of ICP monitoring, and
      were functional in the ICU environment for up to 10 days. Trend patterns recurred
      in this series of SCHI patients: Extreme PbCO2 (high) and pHb (low) are
      associated with poor perfusion; increasing pbCO2 and decreasing pHb may be early
      indicators of ICP crisis, i.e. ICP > 20 mm Hg that tends to be unresponsive to
      therapy, and; pentobarbital "loading" and maintenance is associated with
      increased pbO2. These preliminary results from monitoring pbO2, pbCO2 and pHb in
      SCHI patients indicate that fiber optic sensor technology functions and is able
      to be used in this application. Trend patterns from this data may further
      indicate practical utility as a more direct monitor of the delicate balance
      between tissue perfusion and cell metabolism than ICP alone.

PMID- 9779177
TI  - Determining cerebral perfusion pressure thresholds in severe head trauma.
AB  - Laboratory studies suggest the pulsatile component of the transcranial doppler
      (TCD) waveform may be useful in determining lower autoregulatory threshold. This
      study aimed to assess the effect of increasing CPP on jugular bulb oximetry
      (SjO2) and middle cerebral artery (MCA) TCD flow velocities in the early
      management of severe head injury. 16 severely head injured patients (GCS < or =
      8), had intracranial pressure (ICP), mean arterial pressure, SjO2 and MCA Doppler
      velocity monitored continuously. CPP was increased by intravenous fluids (right
      atrial pressure approximately equal to 10) and supplemented with adrenaline
      infusion until TCD pulsatility (Gosling pulsatility index [PI] reached a plateau.
      The mean CPP at which SjO2 surpassed 55% was 62 +/- 6.2 mm Hg. TCD PI did not
      plateau until a significantly higher mean CPP of 74 +/- 5.1 mm Hg was achieved (p
      < 0.01). In 8 cases, increased CPP was associated with a fall in ICP, ranging
      from 1 to 8 mm Hg. We conclude that a critically low level of SjO2 is a late
      indicator of failed autoregulation. CPP values associated with intact
      autoregulation identified by TCD assessment of MCA flow are significantly higher
      than those indicated by SjO2 monitoring. MCA Doppler flow assessment may be
      useful in determining the level of CPP at which therapy should be aimed in the
      early resuscitation of head trauma.

PMID- 9779180
TI  - Cerebral oxygenation in contusioned vs. nonlesioned brain tissue: monitoring of
      PtiO2 with Licox and Paratrend.
AB  - Brain tissue PO2 in severely head injured patients was monitored in parallel with
      two different PO2-microsensors (Licox and Paratrend). Three different locations
      of sensor placement were chosen: (1) both catheters into non lesioned tissue (n =
      3), (2) both catheters into contusioned tissue (n = 2), and (3) one catheter
      (Licox) into pericontusional versus one catheter (Paratrend) into non lesioned
      brain tissue (n = 2). Mean duration of PtiO2-monitoring with both microsensors in
      parallel was 68.1 hours. Brain tissue PO2 varied when measured in lesioned and
      nonlesioned tissue. In non lesioned tissue both catheters closely correlated
      (delta Licox/Paratrend: mean PtiO2 < 5 mm Hg) after 20 hours post insertion. In
      pericontusional tissue PtiO2 was reduced relative to non lesioned tissue (delta
      lesioned/non lesioned: mean PtiO2: 10.3 mm Hg). In contusioned brain tissue PtiO2
      was always below the "hypoxic threshold" of 10 mm Hg, independent of the type of
      microsensor used. During a critical reduction in cerebral perfusion pressure (<
      60 mm Hg), PtiO2 decreased measured with both microsensors. Elevation of inspired
      oxygen fraction, normally followed by a rapid increase in tissue PO2, only
      increased PtiO2 when measured in pericontusional and nonlesioned brain. To
      recognize critical episodes of hypoxia or ischemia, PtiO2-monitoring of cerebral
      oxygenation is recommended in nonlesioned brain tissue.

PMID- 9779179
TI  - Simultaneous continuous measurement of pO2, pCO2, pH and temperature in brain
      tissue and sagittal sinus in a porcine model.
AB  - INTRODUCTION: The clinical use of brain tissue oxygen measurement in patients
      with severe head injury is increasing. It is important to compare the findings in
      brain tissue with cerebrovenous blood oximetry, to obtain normal values and to
      find out limitations of the method. We evaluated a newly available multisensor
      probe simultaneously in the brain tissue and in the sagittal sinus in a porcine
      animal model. METHODS: We placed the Paratrend 7-probe (BSL, High Wycombe, UK) in
      the left frontoparietal white matter and measured pO2 (PtiO2), pCO2 (ptiCO2), pH
      and temperature while simultaneously measuring these parameters (pcvO2, pcvCO2)
      in the sagittal sinus in 7 pigs under general anaesthesia during oxygen
      enhancement. RESULTS: The relation between oxygen increase in brain tissue and in
      the sagittal sinus showed a coefficient of correlation (CCmean) rmean = 0.96. The
      quantitative response in brain tissue was much more sensitive than in the sinus.
      A close correlation between pCO2 in brain tissue and sagittal sinus and the
      increase of the inspired oxygen was seen: CC ptiCO2 to arterial oxygen pressure
      (paO2) - rmean = 0.67, CC pcvCO2 to paO2 - rmean = 0.88. CONCLUSIONS: Measuring
      partial oxygen pressure in brain tissue is more responsive to physiological
      variations, and the absolute values are more sensitive than oxygen measurement in
      the cerebrovenous compartment. This is important for interpreting measured values
      and introducing new coefficients for patient monitoring.

PMID- 9779181
TI  - Monitoring brain oxygen tension in severe head injury: the Rotterdam experience.
AB  - Cerebral ischemia is considered the central mechanism leading to secondary brain
      damage in patients with severe head injury. We investigated the technique of
      continuous monitoring of local brain tissue oxygen tension as parameter for
      cerebral oxygenation. Eighty-two patients with non penetrating severe head injury
      were studied. No complications of the monitoring technique were seen.
      Postmeasurement calibration of the catheters showed a very low zero drift and
      acceptable sensitivity drift. Low PbrO2 values were seen within the first 12 to
      24 hours of injury. Early occurrence of values below 10 mm Hg indicated a poor
      prognosis. Comparative measurements between two catheters performed in six
      patients showed differences in absolute values measured, but a good correlation
      of relative changes was observed. We conclude that continuous monitoring of PbrO2
      is reliable, clinically applicable and provides the clinician with a better
      insight in cerebral oxygenation and hopefully should help in targeting therapy
      towards improved cerebral oxygenation.

PMID- 9779182
TI  - Expression of immediate early gene c-fos in rat brain following increased
      intracranial pressure.
AB  - No attention has been given to an influence of the intracranial pressure (ICP)
      elevation on the brain at the level of the gene. In the present study, we
      originally attempted to evaluate the molecular biological changes of the brain,
      especially the expression of c-fos mRNA as a marker of cellular response, caused
      by increased ICP. Our results confirm that the neurons and non-neuronal cells are
      well able to tolerate the stress of increased ICP at the level of the gene, under
      the condition that cerebral blood flow (CBF) is maintained. A severe increase in
      ICP, which reduces CBF, enhances the c-fos mRNA expression in a similar fashion
      as in a forebrain ischemia model, except in the choroid plexus.

PMID- 9779183
TI  - Leukocyte adhesion molecule profiles and outcome after traumatic brain injury.
AB  - Adhesion molecules have an important role in leukocyte migration into tissue
      after injury. We hypothesised that changes in ICAM-1 and L-selectin expression
      after traumatic brain injury would result in altered serum concentrations of
      these molecules, which would be related to injury severity and outcome. We
      investigated arterial and jugular venous concentrations of ICAM-1 and L-selectin
      in 22 patients. The Glasgow Coma Score and Injury Severity Score were recorded.
      Paired arterial and jugular venous blood samples were taken at designated times
      after brain injury: on admission, at 24 hours, 48 hours and 96 hours. Glasgow
      Outcome Scores at 6 months were obtained. Mean serum concentrations of ICAM-1
      were normal on admission, but became significantly increased by 96 hours (p =
      0.018). Mean L-selectin concentrations wre markedly below controls at all time
      points (p < 0.001). There were no significant differences between jugular venous
      and arterial concentrations of either ICAM-1 or L-selectin. Serum ICAM-1 was
      significantly related to neurological outcome (p < 0.001) and to the Glasgow Coma
      Score (p < 0.001). These changes in adhesion molecules expression may be
      important in the pathophysiology of secondary injury. The highly significant
      relationship between serum ICAM-1 and neurological outcome suggests that drugs
      which antagonize adhesion molecule activity may improve outcome after traumatic
      brain injury.

PMID- 9779184
TI  - Relevance of calcium homeostasis in glial cell swelling from acidosis.
AB  - Tissue acidosis from trauma or ischemia induces cytotoxic brain edema, mainly
      affecting astrocytes. In vitro, lactacidosis induces a dose-dependent swelling of
      glial cells. Activation of membrane transporters and channels, also involved in
      regulation of intracellular pH (pHi), has been identified as underlying
      mechanism, although details are poorly understood. We have currently studied
      whether Ca(2+)-ions play a role in acidosis-induced glial swelling and the
      associated intracellular acidification. The medium pH of a cell suspension (C6
      glioma) was lowered from control (7.4) to 6.2 by lactic acid. Cell volume (CV)
      and pHi were assessed by flow cytometry. During acidosis in normal medium (2.2 mM
      Ca2+) CV reached a maximum of 125.1%. In a calcium-free medium swelling from
      acidosis was inhibited by 74%, while additional buffering of intracellular
      calcium (Ca2+i) by BAPTA-AM had no further effect. Buffering of Ca2+i alone did
      not affect the CV increase from acidosis at all. pHi which is decreasing during
      acidosis was not influenced by the above modifications. The present experiments
      indicate that lactacidosis-induced glial swelling depends on the presence of
      extracellular Ca(2+)-ions, while alterations of Ca2+i do not seem to be involved.

PMID- 9779185
TI  - Cerebral accumulation of beta-amyloid following ischemic brain injury with long
      term survival.
AB  - Deposits that are recognized by antibodies specific for the C-terminal and beta
      amyloid peptide (beta A) but not the N-terminal sequences of the amyloid
      precursor protein (APP) fragments are present in the extra- and intracellular
      space in ischemic rat brain with 1 year survival. The immunohistochemical profile
      indicates that the APP in these deposits is truncated between the N-terminal and
      beta A and terminates at the C-terminal. This process probably is reaching into
      the extracellular space.

PMID- 9779186
TI  - Diffuse neuronal perikaryon amyloid precursor protein immunoreactivity in a focal
      head impact model.
AB  - Amyloid precursor protein (APP) has been shown to accumulate in traumatically
      injured axons as early as 1 hour after injury. This accumulation may be due to
      interruption of fast axoplasmic transport and/or upregulation of APP synthesis.
      The aim of this study was to examine the neuronal cell body response to head
      impact using APP immunostaining in a focal non-missile head impact model. Ten
      anaesthetised and ventilated 2 year old Merino ewes were subjected to graded
      impact in the left temporal region by captive bolt. 2 hours after impact the
      brain was perfused fixed with formaldehyde. The tissue was mounted in paraffin,
      sectioned and stained with a monoclonal antibody to APP and standard H&E stain.
      APP positivity was semi-quantitated using a modification of our previously
      described sector scoring system [1]. Widespread neuronal APP positivity was found
      in the cerebral hemispheres and brain stem distant from the site of focal injury
      in all 10 animals. The most prominent APP positivity was found in the nerve cell
      bodies of the impacted left cerebral hemisphere. APP positive neurons were also
      found within regions which were structurally normal when stained with H&E. These
      results demonstrate diffuse neuronal perikaryon APP immunoreactivity following a
      focal head impact injury. The expression of APP within the neuronal cell body may
      be due to upregulation of APP synthesis or alterations in the availability of
      epitopes of APP. Further studies are in progress to address these hypotheses.

PMID- 9779187
TI  - Blood-brain barrier permeability, neutrophil accumulation and vascular adhesion
      molecule expression after controlled cortical impact in rats: a preliminary
      study.
AB  - Previous studies in our laboratory have shown that controlled cortical impact
      (CCI) produces an acute inflammatory response in rat brain, including neutrophil
      accumulation and upregulation of cell adhesion molecules. The purpose of this
      study was to compare the time course of acute inflammation to blood-brain barrier
      (BBB) breakdown after (CCI) in rats. METHODS: Male Wistar rats (n = 4-7/group)
      were subjected to CCI (2.5 mm depth, 4 m/s) and injected with Evans-blue dye (2%,
      5 ml/kg) at 30 min, 3.5 h, 7.5 h, or 23.5 h after trauma. 30 min after dye
      injection rats were saline-perfused. BBB permeability was measured by
      spectrophotometric quantitation of Evans-blue in injured brain. Alternate
      cryostat sections from the anterior segment of the injured hemisphere were
      analyzed immunohistochemically for neutrophils (MoAb RP-3 vs rat neutrophils) or
      E-selectin (MoAb vs E-selectin). Neutrophils and E-selectin-positive blood
      vessels were quantitated by light microscopy in 100x cortical and hippocampal
      fields. RESULTS AND CONCLUSIONS: BBB breakdown was maximal early after CCI,
      whereas maximum E-selectin upregulation (8 h) and neutrophil accumulation (24 h)
      occurred later. Events other than acute inflammation initiate BBB permeability
      after CCI. Acute inflammation may contribute to BBB permeability at 4 h to 24 h
      after CCI.

PMID- 9779188
TI  - Intracranial pressure, cerebral perfusion pressure, and SPECT in the management
      of patients with SAH Hunt and Hess grades I-II.
AB  - The objective of our study was to examine the course of intracranial pressure
      (ICP) in patients with SAH Hunt and Hess grades I-II and to analyze the
      relationship between ICP, cerebral perfusion pressure (CPP) and cerebral blood
      flow (CBF). Twenty-three patients were studied. ICP, arterial blood pressure
      (ABP) and CPP were continuously recorded. The measurements of CBF with single
      photon emission computed tomography (SPECT) were performed in fifteen patients,
      who showed TCD flow velocities exceeding 120 cnlJsec. In the first two days after
      SAH four patients (15%) showed a normal ICP, six (25%) patients had a moderate
      increase of ICP ranged from 15 to 25 mm Hg and thirteen (60%) patients had ICP
      values higher than 25 mm Hg. Seven of these patients, with ICP values higher than
      40 mm Hg, showed clinical signs of delayed ischaemia. After the treatment with
      osmotic diuretic, ICP decreased and a clinical improvement was observed with the
      exception of one patient. In this patient, the SPECT study showed middle cerebral
      hypoperfusion concordant with the clinically ischaemic hemisphere. Our study
      showed the utility of the monitoring of these parameters in patients with lower
      grade SAH, because it allows the modulation of the therapeutic approach and
      defines the onset of neurological deficits secondary to cerebral ischaemia in all
      grades of SAH.

PMID- 9779189
TI  - Hyperglycemia induces progressive changes in the cerebral microvasculature and
      blood-brain barrier transport during focal cerebral ischemia.
AB  - Hyperglycemia generally enhances cerebral ischemic injury. Most attention on a
      mechanism has focused on the adverse effect of increased lactate production
      (acidosis) leading to neuronal injury. The effects of hyperglycemia on another
      possible primary target, the cerebral microvasculature, is examined in this
      study. Focal cerebral ischemia was achieved by thread occlusion of the middle
      cerebral artery (MCA). Preischemic hyperglycemia was induced by intraperitoneal
      administration of 50% of D-glucose solution. In contrast to normoglycemic
      controls, glucose-injected rats showed a well demarcated pale infarct after 2 or
      4 hours of ischemia reflecting a reduction in cerebral plasma volume (CPV) to 73
      +/- 9 and 55 +/- 6% of contralateral by 2 and 4 hours respectively. Cerebral
      blood flow (CBF) measured by laser-Doppler flowmetry indicated that after the
      initial decline in CBF with MCA occlusion, hyperglycemia led to a further
      progressive reduction during ischemia. Blood-brain barrier transport measured by
      permeability surface area (PS) product for glutamine was reduced in both
      normoglycemic and hyperglycemic rats. However, the decline was greater in the
      hyperglycemic rats. Hyperglycemia induces progressive cerebrovascular changes and
      affects blood-brain barrier transport during focal cerebral ischemia. These
      changes may contribute to the adverse effects of hyperglycemia in stroke.

PMID- 9779190
TI  - Effects of mild and moderate hypothermia on cerebral metabolism and glutamate in
      an experimental head injury.
AB  - In this study we sought to determine the optimal brain temperature for treating
      compression-induced cerebral ischemia. Six cats each were treated with a deep
      brain temperature of 37 degrees C (control), 33 degrees C (mild hypothermia), or
      29 degrees C (moderate hypothermia). Intracranial pressure (ICP) and cerebral
      blood flow (CBF) were monitored, as were arteriovenous oxygen difference (AVDO2)
      and cerebral venous oxygen saturation (ScvO2). The cerebral metabolic rate of
      oxygen (CMRO2) was calculated. Extracellular glutamate concentration was measured
      by microdialysis. ICP was increased by inflation of an epidural balloon until CBF
      became zero. This ischemia was maintained for 5 min, after which the balloon was
      deflated. Mild hypothermia showed coupled CBF-metabolic suppression, but moderate
      hypothermia resulted in disproportionately increased AVDO2, decreased ScvO2, and
      low CBF/CMRO2 (relative ischemia). Reactive hyperemia after balloon deflation was
      decreased after both mild and moderate hypothermia, as was the tissue volume
      showing Evans blue dye extravasation. Extracellular glutamate increased in
      control animals, an effect most effectively suppressed in the mild hypothermia
      group. These data favor 33 degrees C as the optimal temperature for treating
      compression-related cerebral ischemia.

PMID- 9779191
TI  - Effects of systemic hypothermia and selective brain cooling on ischemic brain
      damage and swelling.
AB  - The present study investigates the neuroprotective effects of temporary mild
      systemic hypothermia and selective brain cooling against focal cerebral
      infarction in the rat and the changes of cortical blood flow, and compares these
      two treatment modalities. In permanent middle cerebral artery (MCA) model, the
      treatments were induced 15 min following the artery occlusion. The animals were
      kept at the desired rectal or brain temperature (about 32 degrees C) for 30 min;
      (each, n = 6) and for 1 hr (each, n = 6), and then allowed to rewarm
      spontaneously, whereas control animals were kept at normothermia throughout the
      experiment. The volumes of brain infarction and edema were assessed 24 hr post
      occlusion. The blood flow of the dorsolateral cortex was monitored by Laser
      Doppler flowmetry (LDF) in the other experiments. Hemispheric infarct volume was
      attenuated only in the animals treated for 1 hr with systemic hypothermia (49.2%,
      P < 0.001) and selective brain cooling (26.7%, P < 0.01). The volume of brain
      swelling was diminished only in the animals treated with systemic hypothermia for
      1 hr (23.6%, P < 0.05). LDF examination revealed a sharp drop in blood flow upon
      MCA occlusion and maintaining in low blood flow throughout the experiment in the
      control and systemic hypothermia. However, in the selective brain cooling, the
      reduced blood flow increased from 40% to 70% of baseline value while the brain
      was rewarmed. The present study indicates that mild systemic hypothermia has much
      stronger protective effects against focal cerebral infarction and edema than
      selective brain cooling. The lack of protective effects of selective brain
      cooling may be caused by post-cooling cerebral hyperemia in the ischemia area.

PMID- 9779192
TI  - Increase in transcranial Doppler pulsatility index does not indicate the lower
      limit of cerebral autoregulation.
AB  - INTRODUCTION: Transcranial Doppler pulsatility index was reported clinically to
      increase when cerebral perfusion pressure decreased, hypothetically marking the
      lower limit of cerebral autoregulation. We sought to investigate the relationship
      between pulsatility index, cerenbrovascular resistance, and cerebral perfusion
      pressure in various states of autoregulation in an animal model of moderate
      intracranial hypertension. METHOD: Eight New-Zealand White Rabbits were studied
      with basilar artery blood flow velocity (ultrasound Doppler) and cortical blood
      flow (laser Doppler) monitored continuously during subarachnoid saline infusion
      to increase intracranial pressure (< 55 mm Hg). Four animals demonstrated a
      stable cortical blood flow, and four demonstrated decreasing blood flow when
      cerebral perfusion pressure decreased. RESULTS: Pulsatility index showed the same
      pattern of increase when cerebral perfusion pressure decreased, independent on
      whether cortical blood flow was stable or falling. The percentage rate of
      increase in the pulsatility index was not different in autoregulating and non
      autoregulating animals. The rate of decrease in cerebrovascular resistance was
      significantly lower (p < 0.05) in non-autoregulating than in autoregulating
      animals. CONCLUSION: The increase in transcranial Doppler pulsatility index when
      cerebral perfusion pressure falls cannot be interpreted as a phenomenon able to
      mark the lower limit of cerebral autoregulation.

PMID- 9779193
TI  - Evaluation of cerebrovascular CO2-reactivity and autoregulation in patients with
      post-traumatic diffuse brain swelling (diffuse injury III).
AB  - The present study was undertaken to elucidate the status of autoregulation and
      CO2-reactivity soon after injury in patients with a post-traumatic diffuse
      bilateral brain swelling. A prospective study was carried out in 31 consecutively
      admitted patients with a severe head injury and a Diffuse Brain Injury type III,
      following the definition stated by the Traumatic Coma Data Bank classification.
      To evaluate CO2-reactivity, AVDO2 was measured before and after ventilator
      manipulations. Assuming a constant CMRO2 during the test, changes in 1/AVDO2
      reflect changes in CBF. Patients with changes in estimated CBF below or equal to
      1% were included in the impaired/abolished CO2-reactivity group. To test
      autoregulation, hypertension was induced using phenylephrine. Arterial and
      jugular blood samples were taken to calculate AVDO2 before and after a steady
      state of MABP was obtained. Cerebrovascular response to CO2 was globally
      preserved in all but two cases (6.5%). In contrast, autoregulation was globally
      preserved in 10 (32.3%) and impaired/abolished in 21 cases (67.7%). Our data do
      not support the premise that increasing cerebral perfusion pressure by inducing
      arterial hypertension is beneficial in those patients with a diffuse brain
      swelling in whom autoregulation is impaired or abolished. Clinical implications
      for treatment are discussed.

PMID- 9779194
TI  - Cortical extracellular sodium transients after human head injury: an indicator of
      secondary brain damage?
AB  - Animal studies indicate that elevated extracellular sodium can increase glutamate
      induced excitotoxicity. Therefore, we investigated the relationship between
      sodium and glutamate and the effect of changes in sodium concentrations on the
      outcome of head-injured patients. Thirty-four (34) patients were selected for
      this study and divided into a group of patients having episodes (> or = 30-min)
      of high sodium in dialysates (> or = 200 mM; HIGH, n = 11) and a group of
      patients having no such episodes (NORMAL, n = 23). Levels for sodium (226 +/- 5.7
      mM), glutamate (12.53 +/- 2.2 microM) and ICP (32.2 +/- 4.0 mm Hg,) were
      relatively high during the high sodium episodes. Overall, mean values for
      glutamate, ICP and outcome did not differ amono both groups. The mean dialysate
      sodium concentration, however, was significantly higher in the HIGH (178 +/- 6
      mM) compared to the NORMAL group (158 +/- 3 mM; p < 0.01). Spearman rank
      correlation between sodium and glutamate or ICP were not significant. The HIGH
      sodium group did not have significantly more patients with poor outcome than the
      NORMAL group. The results indicated sodium concentrations did not affect the
      outcome of head-injured patients. However, other sodium monitoring techniques are
      desirable to elucidate these apparent potentially major sodium transients, which
      we have observed in the human cortex, after severe head injury.

PMID- 9779195
TI  - Intraoperative microdialysis and tissue-pO2 measurement in human glioma.
AB  - The amino acid glutamate is one of the major neurotoxins in the pathogenesis of
      neuronal death after ischemia or trauma. Microdialysis studies in both man and
      animal have shown elevated extracellular levels after primary lesions. Monitoring
      of cerebral tissue oxygenation (p(ti)O2) has been used in recent years to detect
      and prevent episodes of low cerebral oxygenation, e.g. after trauma or
      subarachnoid hemorrhage. Intraoperative monitoring of p(ti)O2 combined with
      microdialysis in the peritumoral edema has been chosen to study the responses of
      glutamate and oxygen levels during resection. In 7/9 patients p(ti)O2 was below
      "critical" 10 mm Hg. Elevating inspiratory oxygen concentration to 100% led to an
      increase of p(ti)O2 by 2.5-4 fold and a decrease of glutamate and aspartate by 50
      80%. A close correlation between p(ti)O2 and microdialysis glutamate levels was
      not clearly shown due to frequent intraoperative manipulations.

PMID- 9779196
TI  - Relationship between excitatory amino acid release and outcome after severe human
      head injury.
AB  - In previous studies, Katayama and our group have documented a massive increase in
      excitatory amino acid release following traumatic brain injury, in both rat fluid
      percussion, and humans [2,5]. To test the hypothesis that the magnitude of this
      "Excitotoxic Surge" plays a significant role in determining 6-month patient
      outcome. We have studied 83 consecutive severely head injured patients at the
      Medical College of Virginia for inclusion into this study. A microdialysis probe
      was placed within the cortex to continuously measure dialysate excitatory amino
      acids (Glutamate and Aspartate), along with several other analytes for
      approximately 5 days after injury. ICP, CPP, and MABP measurements were also time
      linked with each analyte measurement to create a neurochemical, clinical, and
      physiological "profile" for each patient. Outcome was determined by follow up
      using the Glasgow 6-Month outcome scale. A very strong correlation existed
      between the release of the EAA's glutamate and aspartate after TBI (p < 0.0001).
      Patients with significantly elevated mean glutamate values for the entire
      monitoring period were most likely to exhibit elevated levels of ICP. The
      magnitude of glutamate released significantly correlates with 6-month patient
      outcome (p = 0.0234). When patients were subdivided by the CT diagnosis of lesion
      type, we found that those patients with contusions displayed the highest overall
      of EAA's.

PMID- 9779197
TI  - Selective hippocampal damage to hypoxia after mild closed head injury in the rat.
AB  - Our previous studies have shown selective neuronal damage in the CA3 region after
      mild closed head injury (CHI) combined with hypoxia. In the present studies, we
      examined (1) extracellular concentrations of neuroactive amino acids using in
      vivo microdialysis technique and (2) neuroactive amino acid binding to their
      receptors using quantitative autoradiography. Male SD rats were divided into five
      groups; sham control, mild CHI (sacrificed at 1 h or 24 h after CHI), mild CHI
      followed by hypoxia (1 h or 24 h). [3H]-Glutamate binding to NMDA receptors, [3H]
      muscimol binding to GABAA receptors and [3H]-kainate binding to KA receptors were
      measured in hippocampus and cortex by quantitative autoradiography. With CHI
      alone, GLU and TAU levels were transiently increased by 15 min posttrauma. In the
      CHI with hypoxia, increases in GLU and TAU levels were sustained until 60 min
      following CHI. GABA level was also increased until 75 min posttrauma Pretreatment
      of MK-801 significantly diminished the prolonged elevation in GLU and TAU levels.
      (2) CHI alone did not produce prominent change in the measured receptor binding.
      When hypoxia was combined with CHI, significant increase in [3H] GLU binding to
      NMDA receptors and significant decrease in [3H]-muscimol binding to GABAA
      receptors were observed in CA1 and CA3 at 1 h and 24 h post-insult. These results
      demonstrate that selective hippocampal damage to hypoxia after mild CHI may be
      mediated through an increase in NMDA receptor activation and the further release
      of GLU and that NMDA antagonist may be beneficial in preventing secondary
      neuronal damage by hypoxia.

PMID- 9779198
TI  - The use of near infrared spectroscopy (NIRS) in children after traumatic brain
      injury: a preliminary report.
AB  - Children commonly develop diffuse cerebral swelling after traumatic brain injury
      (TBI) which is believed due to a secondary response to the injury. Near infrared
      spectroscopy (NIRS), a continuous, direct, and noninvasive monitor of cerebral
      oxygenation and cerebral blood volume (CBV), could be helpful in understanding
      these secondary responses. The aims of our study were to determine whether NIRS
      used in children with severe TBI will provide insight into the pathophysiology of
      injury. Ten children (1 mo to 15 years old) with severe TBI (admission GCS < or =
      7) were continuously monitored by NIRS by placing optodes over the
      frontalparietal region. Relative values of oxyhemoglobin (HbO2), deoxyhemoglobin
      (Hb), and total hemoglobin (THb) were obtained and compared to intracranial
      pressure (ICP), mean arterial pressure (MAP), electroencephalography (EEG), and
      arterial PCO2 (PaCO2). Episodes of intracranial hypertension (ICP > 20 Torr [T]),
      changes in ICP > 10 T, changes in PaCO2 > or = 8 T, and changes in MAP > 20 T
      frequently resulted in changes in HbO2, Hb, and THb. Hyperventilation with
      decreased PaCO2 always resulted in cerebral oxygen desaturation irregardless of
      ICP. Often, high ICP correlated with increased THb and HbO2 indicating increased
      CBV and cerebrovascular dilatation. In two children, posttraumatic seizures were
      preceded by an unexplained rapid cerebral hyperoxygenation several hours prior to
      the onset of the clinical seizures. NIRS reliably detects changes in cerebral
      hemodynamics in children and may be used to further understand the etiology of
      the diffuse cerebral swelling seen in children after severe TBI.

PMID- 9779199
TI  - Preliminary evaluation of a prototype spatially resolved spectrometer.
AB  - Near infrared spectroscopy (NIRS) has become an established research tool and is
      now being explored in several clinical settings [7]. However, until recently NIRS
      has not been fully quantified and changes have been difficult to interpret [4]. A
      new development by Hamamatsu Photonics, called the Spatially Resolved
      Spectrometer (SRS), proposes to be able to give a quantitative measure of oxygen
      saturation. We have incorporated the SRS into a multimodality monitoring system
      in three different clinical situations: 1) patients undergoing routine
      cardiopulmonary bypass, 2) head injured patients and 3) patients undergoing right
      sided carotid endarterectomy. The importance of this investigation is in the
      development of the SRS machine which shows potential as a useful clinical tool.
      The results demonstrated good correlation between SRS and jugular venous oximetry
      (SjO2) in about 50% of patients. Although these results are encouraging, this
      study suggests that the SRS, in its present form, is not a reliable clinical
      monitor of cerebral oxygen saturation.

PMID- 9779200
TI  - NIRS: dose dependency of local changes of cerebral HbO2 and Hb with pCO2 in
      parietal cortex.
AB  - Regional cerebral oxygenated hemoglobin and total hemoglobin increased
      systematically with increasing depth of hypercapnia, but the concentration of
      deoxygenated hemoglobin remained relatively constant. Relative mean changes of
      oxygenated and total hemoglobin increased nearly linearly, corresponding to the
      characteristic increase of the cerebral vascular dilation with increasing depth
      of hypercapnia.

PMID- 9779201
TI  - Multimodal hemodynamic neuromonitoring--quality and consequences for therapy of
      severely head injured patients.
AB  - Fifty-five head injured patients (GCS < 8) were studied at an average of 7.5 +/-
      3.4 days on the ICU to check quality of hemodynamic monitoring and the
      consequences for therapy. Multimodal neuromonitoring included intracranial
      pressure (ICP), mean arterial pressure (MAP), cerebral perfusion pressure (CPP),
      endtidal CO2 (EtCO2) as well as brain tissue--pO2 (p(ti)O2), regional oxygen
      (rSO2) and jugular venous oxygen saturation (SjO2). Regional p(ti)O2 as well as
      global SjO2 were sensitive technologies to detect hemodynamic changes. However
      analyzing reliability and good data quality regional p(ti)O2 (up to 95%) was
      superior to jugular bulb oximetry (up to 50%). Longterm-measurements of rSO2
      using near infrared spectroscopy reached, if possible, a restricted reliability
      (good data quality up to 70%) and sensitivity in comparison to p(ti)O2.
      Especially p(ti)O2 enabled detection of critical p(ti)O2 (< 15 mm Hg) in up to
      50% frequency during the first days after trauma and a second peak after day 6 to
      8 according to evidence of CPP insults. Knowledge of baseline p(ti)O2 and CO2
      reactivity allowed minimizing risk of ischemia by induced hyperventilation and
      improvement on cerebral microcirculation after mannitol administration could be
      individually recognized.

PMID- 9779202
TI  - Assessment of cerebrovascular reactivity in patients with carotid artery disease
      using near-infrared spectroscopy.
AB  - The aim of this study was to assess Near-infrared spectroscopy (NIRS) as a tool
      for testing CO2 reactivity in patients with carotid occlusive disease. One
      hundred sixty patients were examined (age range 44 to 85 years). Monitored
      parameters included transcranial Doppler flow velocity (FV), changes in
      concentration of oxy-(HbO2) and deoxy (Hb) haemoglobin, cutaneous Laser Doppler
      blood flow (LDF), endtidal CO2, ABP, and SaO2. Hypercapnia was induced using a 5%
      CO2 air mixture for inhalation. To estimate the skin flow contribution to NIRS
      during reactivity testing, the superficial temporal artery was compressed, and
      the NIRS changes in response to the fall in LDF recorded. FV and HbO2 derived
      reactivity values were related to the severity of the stenosis (p = 0.0001 and
      0.021 respectively). The correlation between the two modalities was significant
      (r = 0.47, p < 0.000001). The average estimated skin contribution to NIRS changes
      was 16.5%. Reproducibility of HbO2-reactivity was similar but worse than FV
      reactivity (19.1% and 13.8% variation respectively). The clinical correlations
      improved when our method of correction for skin influence was used. NIRS shows
      potential as an alternative technique for testing CO2 reactivity in patients with
      carotid disease provided the conditions are carefully controlled and the
      contribution from extracranial tissue is taken into account.

PMID- 9779203
TI  - The relationship of pulsatile cerebrospinal fluid flow to cerebral blood flow and
      intracranial pressure: a new theoretical model.
AB  - An electrical-equivalent circuit model of the cerebrovascular system is proposed,
      components of which directly relate to cerebrospinal fluid (CSF) compartment
      compliance and the determination of intracranial pressure (ICP). The model is
      based on three premises: 1) Under normal, physiologic conditions, the conversion
      of pulsatile arterial to nonpulsatile venous flow occurs primarily as a result of
      arterial compliance. Nonpulsatile venous flow is advantageous because less energy
      is required to maintain constant flow through the venous system, which comprises
      75-80% of total blood volume. 2) Dynamic CSF movement across the foramen magnum
      is the primary facilitator by which intracranial arterial expansion occurs.
      Interference of the displacement of CSF during systole results in pulsatile
      venous flow and increased venous flow impedance. 3) Tissue hydrostatic pressure
      (here defined as ICP) is a dependent variable which is a function of capillary
      hydrostatic pressure and the osmotic/oncotic pressure gradient created by the
      blood-brain-barrier (BBB). An interference of transcranial CSF movement results
      in a decrease in cerebral blood flow (CBF) due to inertial effects impeding
      pulsatile venous flow. Feedback regulation in response to this decreased CBF
      leads to arteriolar vasodilatation (decreased resistance), thereby lowering the
      pressure difference between internal carotid and capillary pressures. Assuming no
      changes in the BBB potential, ICP increases linearly as capillary pressure
      increases.

PMID- 9779205
TI  - Pathogenesis of traumatic brain swelling: role of cerebral blood volume.
AB  - The pathogenesis of traumatic brain swelling is unclear. Brain edema (increased
      water content) is considered an important cause of swelling, but there is also
      evidence that vasodilatation with increased cerebral blood volume (CBV) plays a
      role. We have evaluated early posttraumatic changes in CBV in 37 head-injured
      patients, using dynamic contrast-enhanced computerized tomography (CT) in
      combination with stable Xenon-enhanced CT for measurement of cerebral blood flow
      (CBF). This technique enables rapid determination of CBV without interfering with
      patient care. CBV values ranged from 2.0 to 10.1 ml/100 g. There was no
      relationship the time after injury at which the measurements were taken. CBV did
      not correlate with CBF in the early posttraumatic period. Patients with raised
      ICP (> 20 mm Hg) had significantly higher CBV that patients with normal ICP (5.4
      +/- 2.1 vs 3.7 +/- 0.9 ml/100 g). Yet, the presence of signs of brain swelling on
      CT had no relation to the level of CBV. These data suggest that increased CBV may
      contribute to raised ICP, but that brain swelling is not caused by increased CBV
      alone, and is more likely accounted for by brain edema. We speculate that
      cerebral energy failure is the unifying cause of both intracellular edema and
      cerebral vasodilation leading to swelling of brain tissue.

PMID- 9779204
TI  - Indices for decreased cerebral blood flow control--a modelling study.
AB  - Time-dependent interactions between pressure, flow and volume of cerebral blood
      and cerebrospinal fluid were mathematically modelled. The model was designed to
      simulate blood inflow and storage, arteriolar and capillary blood circulation
      controlled by cerebral autoregulation, venous blood outflow and storage modulated
      by intracranial pressure, and cerebrospinal fluid production, storage and
      reabsorption. The software implementation of the model was used to calculate the
      response to a gradual decrease in cerebral perfusion pressure corresponding to
      either systemic hypotension or intracranial hypertension. We computed flow
      pulsatility index (PI) and short range correlation coefficients between systolic,
      diastolic and mean flow velocity (FVs,d,m) and mean cerebral perfusion pressure
      (CPP). In simulation, the changes in cerebral flow produced by intracranial
      hypertension and systemic hypotension were practically indistinguishable. The
      relationship between PI and CPP was reciprocal, independent of the state of
      autoregulation. The short range running correlation coefficients between FVs, FVm
      and CPP indicated both combined safe CPP range and preserved autoregulation,
      promising a clear clinical detection of "non-worsening" blood supply conditions.
      A similar procedure was applied to selected clinical data to illustrate the
      theoretical considerations.

PMID- 9779206
TI  - Subdural monitoring of ICP during craniotomy: thresholds of cerebral
      swelling/herniation.
AB  - It is possible to define thresholds for cerebral swelling or herniation during
      craniotomy. In 178 patients subjected to craniotomy for space occupying processes
      subdural ICP was measured before opening of dura. The subdural ICP was correlated
      to the degree of cerebral swelling or herniation after opening of dura. At
      subdural ICP < 7 mm Hg cerebral swelling/herniation after opening of dura rarely
      occurs, while at ICP > or = 10 mm Hg cerebral swelling/herniation occurs with
      high probability. These ICP thresholds are independent of the pathophysiology
      (SAH, cerebral tumor), the anaesthetic agent (isoflurane, propofol) and the PaCO2
      level (< or = 4.0 kPa, > 4.0 kPa). Generally, a good correlation between the
      tactile estimation of dural tension and the tendency to cerebral swelling or
      herniation after opening of dura was found. However, in 8.5% the surgeons were
      unable to predict swelling/herniation.

PMID- 9779207
TI  - ICP during anaesthesia with sevoflurane: a dose-response study. Effect of
      hypocapnia.
AB  - In patients with a supratentorial cerebral tumor, an increase in sevoflurane
      concentration from 1.5% (0.7 MAC) to 2.5% (1.3 MAC) did not change the
      intracranial pressure (ICP) significantly (12 to 14 mm Hg (medians)). However, a
      significant increase in cerebral blood flow (CBF) from 29 to 39 ml/100 g/min
      (medians) was disclosed. During administration of sevoflurane 1.5% and 2.5%, a
      significant decrease in ICP (3.5 and 3.0 mm Hg (median) respectively) was found
      when PaCO2 was decreased by 0.8 kPa.

PMID- 9779208
TI  - Radiation-induced blood-brain barrier changes: pathophysiological mechanisms and
      clinical implications.
AB  - The pathophysiology of whole-brain radiation (WBR) toxicity remains incompletely
      understood. The possibility of a primary change in blood-brain barrier (BBB)
      associated with microvascular damage was investigated. Rats were exposed to
      conventional fractionation in radiation (200 +/- cGy/d, 5d/wk; total dose, 4,000
      cGy). BBB changes were assessed by means of the quantitative 14C-alpha
      aminoisobutyric acid (AIB) technique coupled with standard electron microscopy
      (EM) and morphometric techniques as well as studies of the transcapillary passage
      of horseradish peroxidase (HRP). At 15 days after WBR, AIB transport across BBB
      increased significantly in cerebral cortex. EM disclosed vesicular transport of
      HRP across the intact endothelium without opening of the tight junctions. Ninety
      days after WBR, well-defined alterations of the microvasculature were observed.
      The main feature of cortical microvessels was their collapsed aspect, associated
      with perivascular edema containing cell debris. Data suggest a possible
      association between damage of the microvascular/glial unit of tissue injury and
      development of radiation-induced brain cerebral dysfunction. We hypothesize the
      following sequence of pathophysiological events: WBR causes an early increase in
      BBB permeability, which produces perivascular edema and microvascular collapse.
      The interference with microcirculation affects blood flow and energy supply to
      the tissue, resulting in structural damage on an ischemic/dysmetabolic basis.

PMID- 9779209
TI  - Correlation coefficient between intracranial and arterial pressures: a gauge of
      cerebral vascular dilation.
AB  - With the use of a laboratory model, arterial and intracranial pressure signals
      were obtained under conditions of varying depths of hypercapnia ranging from
      normocapnia to deep hypercapnia. Also, with the use of a closed cranial window,
      measures of cerebral arteriolar diameter and estimates of cerebral venous flow
      were obtained. The correlation of the intracranial and arterial pressure signals,
      arteriolar diameter, and estimates of venous flow exhibit a dose-dependent
      characteristic by increasing monotonically with increasing progressive states of
      increasing hypercapnia. These results indicate that the correlation between
      intracranial and arterial pressure signals provides an estimate of the gauge of
      the cerebral vasculature.

PMID- 9779210
TI  - Pathogenesis of the mass effect of cerebral contusions: rapid increase in
      osmolality within the contusion necrosis.
AB  - The non-hemorrhagic mass effect of cerebral contusions is commonly attributed to
      vasogenic edema and/or cytotoxic edema (cellular swelling). We propose that a
      marked increase in osmolality within the contusion necrosis proper, in which the
      cellular elements uniformly undergo shrinkage, disintegration and homogenation,
      represents an important and unique mechanism underlying the contusion edema. The
      present study demonstrates in a rat model of cerebral contusion, that 1) the
      osmolality of the contused brain tissue increases rapidly, 2) the increase in
      osmolality is not caused by changes in inorganic ion contents, suggesting a
      metabolic production of osmoles or release of idiogenic osmoles, and 3) the
      contused brain tissue strongly attracts water, provided that blood supply is
      maintained. We suggest that the primary driving force of water accumulation into
      contused brain tissue is the elevated colloid osmotic potential of contusion
      necrosis.

PMID- 9779211
TI  - Control of ICP and the cerebrovascular bed by the cholinergic basal forebrain.
AB  - The involvement of the cholinergic basal forebrain in the control of ICP and the
      cerebrovascular bed was investigated by simultaneous measurement of CBF, BP, ICP
      and ETCO2 in rats and cats. Single unit spikes were also continuously recorded
      during ICP changes in the dorsomedial hypothalamic nucleus (DMH) of cats.
      Glutamate or acetylcholine (Ach) microinjection into the magnocellular basal
      nucleus (nucleus basalis Meynert: NBM, substantia innominata: SI) of rats or the
      DMH of cats caused persistent increases in ICP associated with slightly decreased
      BP. Microinjection of Ach into the NBM or the DMH also induced consistent
      increases in CBF in the cerebral cortex. Spike activities in DMH neurons
      increased before and during spontaneous ICP elevation. The firing rate of the DMH
      neurons increased in phase with the plateau wave-like ICP variations elicited by
      microinjection of Ach into the cholinoceptive pontine area or the contralateral
      DMH. Glutamate- or Ach-induced increases in ICP resulted from an increased CBV in
      response to a reduced cerebral vasoconstrictor tone. Activity within the
      cholinergic basal forebrain, as well as the central noradrenergic system,
      contribute to ICP changes and may be the intrinsic neuronal origin of the plateau
      waves occurring in some pathological conditions.

PMID- 9779212
TI  - The relationship of vasogenic waves to ICP and cerebral perfusion pressure in
      head injured patients.
AB  - Slow vasogenic waves are characterised by sudden rises and falls in both the mean
      ICP and its cardiac pulsatile amplitude for periods of up to an hour. On
      reviewing the on-line computer records of a series of 200 consecutive head
      injured patients, some 650 waves with increases in mean ICP of at least 15 mm Hg
      were recognized. The mean ICP, pulsatile amplitude, perfusion pressure, arterial
      pressure and pulse rates which had been generated every minute were reviewed in
      each of a 100 randomly selected waves in the hopes of allocating them into
      defined groups according to precipitating factors. We had expected to find that
      the majority of waves were precipitated by a preceding fall in cerebral perfusion
      pressure as a result of a transient arterial hypotension. Only in 19 of the 100
      waves did this sequence become apparent and in the remainder, no recognizable
      precipitating factors were found. In 21 of the records, there was a fall in ICP
      of at least 5 mm Hg before the onset of the pressure wave.

PMID- 9779213
TI  - CSF dynamics in a rodent model of closed head injury.
AB  - Using ICP measurements and the bolus injection technique dynamic parameters of
      the cerebrospinal fluid system as there are pressure-volume-index (PVI) and
      resistance to CSF outflow (Rout) were investigated in a new model of diffuse
      closed head injury (CHI) in the rat. It was found that in the absence of brain
      oedema and ICP alterations an increase in PVI and Rout was present in the early
      (4h) period following head injury. This may be indicative for a reduction in
      cerebral blood flow and cerebral blood volume, both shown previously to occur
      after CHI. Furthermore an early impairment of CSF absorption mechanisms is
      evident. To answer the question, whether bolus injection techniques are advisable
      for clinical routine and whether results might have a predictive value, further
      investigations covering longer observation intervals and in the presence of
      secondary insults to the brain are necessary.

PMID- 9779214
TI  - Magnetic resonance imaging studies with cluster algorithm for characterization of
      brain edema after controlled cortical impact injury (CCII).
AB  - Objective of this study was the characterization of traumatic brain injury
      induced by a "Controlled Cortical Impact" with magnetic resonance imaging
      techniques. The impact was applied to the intact dura of the left hemisphere in
      Sprague-Dawley rats. The pneumatic impactor was accelerated to a velocity of 7
      m/s contusing the left temporo-parietal hemisphere to a depth of 2 mm.
      Posttraumatic hemispheric swelling and water content were determined
      gravimetrically, Evans Blue extravasation photometrically, and volume of ischemia
      by TTC-staining and planimetry. Magnetic resonance imaging was performed by a
      Bruker biospec 24/40, 90 min, 24 and 72 h post trauma using a T2w RARE sequence,
      a T1w sequence, before and after application of contrast agent, and a set of
      diffusion weighted images for calculation of ADC-maps. Data analysis was
      performed using a cluster algorithm enabling to interpret corresponding image
      pairs simultaneously. T2w imaging indicates the maximum edema about 24 h post
      trauma. Blood-brain barrier damage, detected by T1w imaging, is more predominant
      in the early posttraumatic phase. The cluster algorithm detects different edema
      components: from the necrotic core to the perifocal vasogenic rim. MRI in
      combination with the cluster algorithm will hopefully be a valuable tool in
      testing neuroprotective agents.

PMID- 9779215
TI  - Estimation of the main factors affecting ICP dynamics by mathematical analysis of
      PVI tests.
AB  - A simplified model of intracranial dynamics is used to reproduce the intracranial
      pressure (ICP) time pattern in 20 patients with severe brain damage during PVI
      tests. A comparison of model responses and clinical tracings was achieved by
      minimizing a least square criterion function and adjusting just 5 parameters.
      These are: the CSF outflow resistance, the intracranial elastance coefficient,
      the autoregulation gain and time constant, and the basal values of arteriolar
      compliance. Based on the value of the autoregulation gain, the patients were
      classified into two groups: those with damaged autoregulation (8 out of 12) and
      those with preserved autoregulation (12 out of 20). Finally, analysis of the
      correlation between parameter estimates provided suggestions on the combination
      of a parameter changes which may have the greater impact on ICP in the individual
      cases. Once these parameters have been identified, they may become possible
      targets for therapeutic interventions.

PMID- 9779216
TI  - Brain tissue pressure gradients are dependent upon a normal spinal subarachnoid
      space.
AB  - Reports from our laboratory have shown that regional brain tissue pressure (RBTP)
      gradients develop in response to supratentorial but not posterior fossa
      extradural masses. We undertook this experiment to discover the mechanism of this
      differing response. RBTP was measured in the right and left frontal lobes (RF,
      LF), temporal lobes (RT, LT), midbrain (MB), and cerebellum (CB) of ten pigs.
      Balloons were expanded in the epidural space at C2 to occlude the subarachnoid
      space. A temporal extradural mass was expanded incrementally. The C2 balloon was
      deflated after temporal mass expansion. Expansion of the cervical balloon
      resulted in a homogeneous rise in RBTP. Expansion of the temporal mass resulted
      in the development of small RBTP gradients with the following relationship: RT >
      LT = LF > RF = CB > MB. In comparison with a previous series of animals without
      cervical balloons, animals in this series demonstrated higher global ICP in
      response to equal size masses and smaller RBTP gradients. Cervical balloon
      deflation resulted in decreased global ICP and increased RBTP gradients. The
      development of RBTP gradients in response to expanding supratentorial masses
      therefore appears to be at least partially dependent upon the presence of a
      normal communication between the supratentorial space and the spinal subarachnoid
      space.

PMID- 9779217
TI  - Resolution of experimental vasogenic brain edema at different intracranial
      pressures.
AB  - Resolution of vasogenic brain edema was examined using the infusion edema model
      in rabbits. Texas Red-albumin (MW 66,000 D) and sodium fluorescein (MW 376 D)
      dissolved in artificial cerebrospinal fluid (aCSF) were infused into the white
      matter of the left frontal lobe of the brain. To quantify the edema fluid cleared
      by the ventricular system, ventriculo-cisternal perfusion was performed with
      aCSF. A closed cranial window, implanted above the left parietal brain, served
      for studying resolution of the artificial edema fluid via the subarachnoid space.
      CSF-samples were collected in 30 minutes-intervals and analysed with a
      spectrophotometer. Clearance of edema fluid was examined under low (2-5 mm Hg),
      medium (9-12 mm Hg), or high (14-17 mm Hg) intracranial pressures (ICP). In the
      low pressure-group, both edema fluid markers were found in the ventriculo
      cisternal and subarachnoid perfusate at 60 and 90 min, in the group with
      moderately increased ICP at 90 and 120 min, respectively. In the high ICP-group
      both fluorescence dyes appeared not less than 90 min in the ventricular system,
      while no increase at all could be found in the subarachnoid space. Our results
      imply that resolution of edema fluid via both the ventricular system and the
      subarachnoid space depends on the actual ICP level.

PMID- 9779218
TI  - Jugular saturation (SjvO2) monitoring in subarachnoid hemorrhage (SAH).
AB  - Jugular saturation (SjvO2) monitoring was performed in 26 SAH patients to
      evaluate the incidence of normal (0.56-0.74) and pathological SjvO2 values in
      this population and to describe its time course in the first 12 days. We also
      attempt to quantify the influence of systemic and cerebral hemodynamics on SjvO2
      and to assess the relationship between cerebral injury volume measured on CT scan
      and SjvO2. Mean SjvO2 was 0.66 +/- 0.07 (354 samples, median 0.67, range 0.43
      0.89). 73% of the observations (259/354) were in the normal range. On serial
      measurements, we identified only 37/354 (10%) desaturation episodes (D.E.). ICP
      was significantly higher during low SjvO2 observation (p = 0.008). No statistical
      differences were noted regarding the influence of MAP, CPP, PaCO2, PaO2 on SjvO2
      but during D.E., lower PaCO2 and CPP were more frequently observed. CT scan
      lesions > 25 ml were associated initially with lower SjvO2 values and with higher
      values at second CT.

PMID- 9779219
TI  - Complications of internal jugular vein retrograde catheterization.
AB  - We report on the incidence of complications of 172 internal jugular vein
      retrograde catheterizations (IJVRCs) performed on 126 patients. Standard
      cannulation and X-ray control of the catheter tip placement were performed.
      Difficulties encountered during the manouvre were registered. Patients with a
      jugular catheter in place for more than one day had neck echography on catheter
      removal and one week later. Carotid artery puncture occurred in 20 (12%) cases
      and lymphatic vessel puncture in one. In 13 (8%) cases IJVRC failed due to
      difficulties in advancing the guide. X-ray films documented catheter misplacement
      in 39 (23%) cases: loop into the internal jugular vein in 11 (6%); paravertebral
      venous plexus cannulated in one; other extracranial jugular afferent cannulated
      in 4 (2%); catheter tip into the jugular lumen in 10 (6%); catheter tip beyond
      the jugular bulb in 13 (8%). First neck echography documented: one perivascular
      hematoma (absent one week later); 3 (4%) jugular vein thrombosis (2 asymptomatic
      and absent one week later; one symptomatic and still evident one week later).
      Positive neck echography was not associated with difficulties, length of
      catheterization, diameter of the catheter. IJVRC is a simple and safe procedure
      with a low incidence of serious complications.

PMID- 9779220
TI  - Jugular bulb monitoring of cerebral oxygen metabolism in severe head injury:
      accuracy of unilateral measurements.
AB  - To investigate the accuracy of unilateral jugularvenous monitoring, we performed
      bilateral jugularvenous monitoring in 22 comatose head injured patients.
      Fiberoptic catheters were placed upstream in both internal jugular veins and
      advanced into the jugular bulbs. Arterial and bilateral jugularvenous blood
      samples were obtained simultaneously for in vitro determination of jugularvenous
      oxygen saturation (SJO2), arterial minus jugularvenous lactate content difference
      (AJDL) and modified lactate-oxygen-index (mLOI). Ischemia was assumed, if one of
      the following pathologies occurred at least unilaterally: SJO2 < 55%, AJDL < 
      0.37 mmol/L, mLOI > 0.08. The mean and maximum bilateral SJO2 differences varied
      between 1.4% to 21.0%, and 8.1% to 44.3% respectively. The bias and limits of
      agreement (mean differences +/- 2SD) between paired samples were -0.4% +/- 12.8%.
      Regarding AJDL bias and limits of agreement were -0.01 mmol/L +/- 0.18 mmol/L. At
      best 87% of defined ischemic events could be evaluated by monitoring at the side
      of predominant lesion or, in diffuse injuries, at the side of the larger jugular
      foramen in CT scan (CT approach). We conclude, due to the wide limits of
      agreement in bilateral SJO2 and AJDL the reliability of unilateral jugularvenous
      monitoring in patients with intracranial pathology is questionable. For
      diagnosing ischemia the CT approach has the highest sensitivity and is therefore
      recommended.

PMID- 9779221
TI  - Comparison of Pcsf monitoring and controlled CSF drainage diagnose normal
      pressure hydrocephalus.
AB  - We evaluated 86 patients for possible normal pressure hydrocephalus (NPH) by: 1)
      CSF pressure (Pcsf) monitoring and analysis for percent of time with A or B
      waves, and 2) controlled CSF drainage for 3 days via a lumbar subarachnoid
      catheter. Clinical outcome after CSF drainage and shunt surgery was assessed as
      change of clinical exam, with grades of none, minor, moderate, or marked change.
      For outcome analysis in 47 patients after shunt surgery, NPH was defined as
      moderate or marked clinical improvement. We assessed the diagnostic
      discrimination of percent-of-time thresholds of A and B-waves for 38 patients. At
      10%, sensitivity for NPH is 91%, specificity is 13%, positive predictive value
      (PPV) is 62%, and the false positive rate is 38%. At the 25% threshold,
      sensitivity is 78%, specificity is 40%, PPV is 67%, false positive rate is 33%,
      and the false negative rate is 22%. For CSF drainage (threshold of minor
      improvement or better), the sensitivity is 97%, specificity is 60%, PPV is 84%,
      negative predictive value (NPV) is 90%, and the false negative rate is 3%. We
      conclude: 1) clinical response to controlled CSF drainage accurately predicts the
      outcome after shunt surgery in patients suspected of having NPH, and 2) A or B
      waves poorly predict which patients will respond to shunt surgery. Three days of
      CSF drainage seems to encompass critical thresholds of CSF volume removal or
      duration of Pcsf reduction necessary for neuronal function to begin returning and
      symptoms to begin resolving in patients with NPH.

PMID- 9779222
TI  - Does CSF outflow resistance predict the response to shunting in patients with
      normal pressure hydrocephalus?
AB  - The value of the measurements of CSF outflow resistance (Rcsf) relative to
      predicting outcome after shunting was studied. In a group of 101 patients with
      mainly idiopathic normal pressure hydrocephalus (NPH) Rcsf was obtained by lumbar
      constant flow infusion. Gait disturbance and dementia were quantified using an
      NPH scale (NPHS) and disability by the Modified Rankin scale (MRS). Patients were
      assessed before and at 1, 3, 6, 9 and 12 months after surgery. Outcome measures
      were differences between the preoperative and last NPHS and MRS scores.
      Improvement was defined as a change of > or = 15% in NPHS and > or = 1 grade in
      MRS. Intention-to-treat analysis of all patients at one year yielded improvement
      of 57% in NPHS and 59% in MRS. Efficacy analysis, excluding comorbidity unrelated
      to NPH, revealed positive predictive values of around 80% at Rcsf < 18, and
      between 90% and 100% at Rcsf > or = 18 mm Hg/ml/min. For Rcsf > or = 18, the
      likelihood ratios were also higher. We conclude that the best predictor of the
      response to shunting is an Rcsf > or = 18 mm Hg/ml/min. Since two-thirds of the
      patients with Rcsf < 18 showed improvement as well, these patients should not be
      denied shunting.

PMID- 9779223
TI  - Hydrodynamic properties of hydrocephalus shunts.
AB  - Hydrodynamic properties of hydrocephalus shunts are not always properly
      characterized by the manufacturer. Therefore, the choice of the shunt should be
      made, by matching performance of the shunt to the disturbed profile of CSF
      circulation of a given patient. The aim of the present shunt evaluation study is
      to evaluates all types of shunts presently in use in the U.K. and make this
      information available to neurosurgeons. Ten most common models of valves have
      been tested to date: Medtronik PS Medical: Delta Valve, Flow Control Valves and
      Lumbo-Peritoneal Shunt, Heyer-Schulte: In-line, Low Profile and Pudenz Flushing
      Valve, Codman: Medos-Programmable, Hakim-Precision, Sophy Programmable Valve,
      Cordis Orbis-Sigma. Our results show the majority of valves have low hydrodynamic
      resistance (exception: PS Lumboperitoneal, Orbis-Sigma), which increase by 100
      200% after connection of a long distal catheter. A few shunts with siphon
      preventing mechanism (Delta, Hayer-Schulte Low Profile, Pudenz-Flushing) offer
      reasonable resistance to negative outlet pressures, however, these valves may be
      blocked by raised subcutaneous pressure. All programmable valves are susceptible
      to siphoning. Programmed settings may be changed by external magnetic field.

PMID- 9779224
TI  - Cine phase-contrast MR imaging in normal pressure hydrocephalus patients:
      relation to surgical outcome.
AB  - Phase-contrast cine MR flow imaging through the aqueduct was used to establish
      the diagnosis of normal pressure hydrocephalus (NPH), and to predict outcome
      after shunting. From 1990-1994 16 patients, who were participants in the Dutch
      Normal Pressure Hydrocephalus Study [3], were studied. The patients included in
      this study met clinical and CT-scan criteria as described in this study,
      underwent cine phase-contrast MR imaging prior to placement of a CSF shunt, and
      had a follow-up 12 months after the operation. Claustrophobic patients, patients
      with a pacemaker or extremely agitated patients were excluded. Normal Flux was
      calculated in each patients, as the average difference in caudal and rostral flux
      (Fdiff) +2 times standard deviation (0.97 cc/sec) [2]. The clinical outcome was
      measured with a modified scale of activities of daily living (ADL) as described
      by Rankin. Of the 16 patients, 8 could not be evaluated due to restlessness
      during MR measurements, disabling cerebral vascular accidents or death before the
      end of the follow-up period. Of the remaining 8 patients, 5 had a normal flux, of
      which only one improved. Two patients had a Fdiff twice the normal range, which
      improved in both patients. One patient had no measurable flux, consistent with an
      aqueduct stenosis; he too improved. Overall, there was a concordance of MR
      findings with final outcome after shunting in 7 out of 8 patients. This pilot
      study, therefore, support the need to further evaluate flow with MR imaging
      techniques to select patients with shunt responsive NPH.

PMID- 9779225
TI  - Cine MR CSF flow study in hydrocephalus: what are the valuable parameters?
AB  - To evaluate the changes of intracranial cerebrospinal fluid (CSF) dynamics in
      hydrocephalus, we studied the various parameters of cine phase contrast (PC)
      magnetic resonance (MR) CSF flow images in cases of acutely progressive
      hydrocephalus, comparing them with those in normal CSF circulation. The MR images
      were obtained with 1.5 T unit using the 2 dimensional cine PC sequence with
      cardiac gating in 10 non-obstructive hydrocephalus (NOH), 3 obstructive
      hydrocephalus (OH), and 10 controls. The temporal velocity information from the
      anterior and posterior cervical pericord spaces, third and fourth ventricles, and
      aqueduct were plotted as wave form. The wave forms were analyzed for
      configurations, amplitude parameters (Smax, Smin, Sdif), and temporal parameters
      (R-S, R-SMV, R-D, R-DMV). The statistical significance of each parameter was
      examined with paired t-test. All patients with OH underwent endoscopic thrid
      ventriculostomy, whereas all NOH underwent shunting procedures. In 5 ROIs,
      distinct reproducible configuration features were obtained at aqueductal and
      cervical pericord spaces. Statistically significant differences between control
      and hydrocephalus only in temporal parameters were determined. In NOH, the graph
      showed R-DMV shortening (p < 0.01) at anterior cervical pericord space. In OH,
      there were R-DMV shortening (p < 0.05) at anterior cervical pericord space, R-SMV
      shortening (p < 0.02) at posterior cervical pericord space. Also the level of
      obstructions could be determined in all OHs. The analysis of MR CSF flow images
      may give us valuable information on the site of obstruction, explaining the cause
      of hydrocephalus, thus deciding the necessity of shunting procedures using in
      vivo images.

PMID- 9779226
TI  - Cerebral blood flow in chronic hydrocephalus--a parameter indicating shunt
      failure--new aspects.
AB  - Prediction of outcome after shunt-therapy in chronic hydrocephalus syndrome is
      uncertain. Pathology reveals an impairment of cerebral blood flow (CBF). Based on
      this, we evaluated CBF and its significance for the assessment of prognosis. In
      21 patients (mean age 69 years) selected for surgery, CBF was measured by PET
      (15O-H2O) before, about one week and 7 months (n = 14) after shunting. CBF was
      computed by a 1-compartmental model in the territories of the ACA, MCA and PCA.
      One PET slice in the height of the maximum projection of both cellae mediae was
      chosen. CBF data were standardized by cluster analysis. Three CBFClusters with
      significantly different CBF levels prior to shunting in the ACA, MCA and PCA
      territory, respectively, referred to the sample average (38.2 ml/100 ml/min) were
      found. These CBFClusters differed in clinical outcome: almost 50% and 90% of
      patients improved clinically in CBFCluster I, with a perfusion level lower than
      average, after one week and 7 months, respectively. In contrast, patients of
      CBFCluster II with an average perfusion did not improve. CBF changes 7 months
      after shunting related to global CBF before surgery showed a relationship with
      the clinical course. Clinical outcome corresponded with preoperative global CBF
      values. Cerebral blood flow lower than average forecasts clinical improvement.
      Our results suggest that measurement of CBF adds to the indication for surgery.

PMID- 9779227
TI  - Quantitative analysis of CSF flow dynamics using MRI in normal pressure
      hydrocephalus.
AB  - In order to clarify the flow dynamics of cerebrospinal fluid (CSF) in normal
      pressure hydrocephalus (NPH), a phase-contrast cine magnetic resonance (MR)
      imaging technique with retrospective cardiac gating was used to measure the
      quantitative flow velocity of CSF in the aqueduct in patients with NPH after
      subarachnoid hemorrhage (SAH-NPH group, n = 17), idiopathic NPH (1-NPH group, n =
      2), asymptomatic ventricular dilatation or brain atrophy (VD group, n = 7) and
      healthy volunteers (control group, n = 19). Intracranial pressure (ICP) and
      pressure volume response (PVR) were also measured during the shunt operation in
      six of the SAH- NPH group. The maximum CSF flow velocity (Vmax) in the aqueduct
      was significantly larger in the SAH-NPH group (9.21 +/- 4.12 cm/sec, mean +/- SD)
      than in the control group (5.27 +/- 1.77, p < 0.001) and the VD group (4.06 +/-
      1.81, p < 0.005). Vmax was not different between the control and VD groups. There
      was a positive correlation between the PVR and the peak CSF flow velocity in the
      SAH-NPH group. These findings suggest that the changes of CSF flow velocity in
      the SAH-NPH group might be caused by a moderate decrease of intracranial
      compliance. The CSF flow study using MRI is useful to differentiate NPH from
      brain atrophy or asymptomatic ventricular dilatation and also to estimate the
      intracranial compliance.

PMID- 9779228
TI  - Magnetic resonance imaging, unstable intracranial pressure and clinical outcome
      in patients with normal pressure hydrocephalus.
AB  - To identify features on magnetic resonance imaging (MRI) scans that are
      associated with unstable intracranial pressure (ICP) and outcome after CSF
      shunting in patients with NPH, we reviewed MRI scans of 17 patients who had
      continuous ICP monitoring performed prior to ventriculo-peritoneal shunt
      insertion. We evaluated the association between periventricular/deep white matter
      lesion burden, focal impingement of the corpus callosum, aqueductal CSF flow
      void, and B-waves with outcome after shunting. The change in neurological
      function between pre- and post CSF shunting evaluation was scored according to a
      standard scale (range -3 or +3). Patients were divided into those with clinical
      improvement (score > 0) or without improvement (score < or = 0) after shunt
      surgery. Focal impingement of the corpus callosum was more frequent in patients
      who improved after CSF shunting compared to those without improvement (8 of 13 vs
      0 of 4, p = 0.05). Patients with focal impingement of corpus callosum had more B
      wave time than those without impingement (60.5% vs 24.7%, p = 0.02). Focal
      impingement of corpus callosum on MRI may be associated with unstable
      intracranial pressure in patients with NPH and may be useful in identifying
      patients who will benefit from CSF shunting.

PMID- 9779229
TI  - Clinical significance of ventricular size in shunted-hydrocephalic children.
AB  - For maintaining the intracranial buffering capacity against shunt obstruction, we
      tried to seek the most suitable size of the lateral ventricles in hydrocephalic
      children. Thirty-seven shunted-hydrocephalic children who required emergent
      revision of the shunt were analyzed. At the time of shunt obstruction, the
      lateral ventricle remained small (0.35 or less than 0.35 on the Evans' index) in
      13 patients (Slit-like group), but it enlarged (more than 0.35 on the Evans'
      index) in 24 patients (Dilated group). The mean age in the Slit-like group was
      significantly older than in the Dilated group and there was no patient younger
      than 3 years in the Slit-like group. Compared with the Dilated group, the Slit
      like group showed significantly rapid deterioration into lethargy after shunt
      obstruction. Also, at the time of obstruction CT scans showed a significantly
      higher rate of narrowing of the ambient cistern. While the shunt was working well
      before shunt obstruction, the Evans' index was less than 0.33 in all patients of
      the Slit-like group. In conclusion, because small ventricles after shunt strongly
      suggest the presence of ventricular tautness, the lateral ventricular size should
      be maintained at more than 0.33 on the Evans' index in shunted children at an age
      of 3 or more than 3 years.

PMID- 9779230
TI  - Dual-switch valve: clinical performance of a new hydrocephalus valve.
AB  - The Dual-Switch valve (DSV) is the first construction on the market which changes
      between two different valve-chambers in parallel depending on the posture of the
      patient. In the lying position the valve acts like a conventional differential
      pressure valve, in the vertical position the high-pressure chamber only opens,
      when the pressure exceeds the hydrostatic pressure difference between the
      formanen of Monro and the peritoneal cavity. The new device has been implanted in
      32 adult patients with hydrocephalus of different etiology. The clinical results
      are excellent to good accompanied by a remarkable slight reduction of the
      ventricular size. Apart from one case with a nonsymptomatic transient hygroma, we
      saw no valve related complications like overdrainage, underdrainage or
      dysfunction. Contrary to conventional differential-pressure valves, adjustable
      devices and other hydrostatic constructions like the Anti-Siphon-device (ASD) or
      Deltavalve, the DSV reliably controls the IVP independently of the posture of the
      patient, the CSF viscosity or the subcutaneous pressure. In contrast to the Orbis
      Sigma-valve (OSV) or the Diamond-valve, the DSV does not control the flow but the
      physiological IVP avoiding the increased risk of mechanical failure. The results
      of this study give strong evidence that the shunt-therapy of adult hydrocephalic
      patients can be significantly improved by the DSV.

PMID- 9779231
TI  - CSF dynamics in a patient with a programmable shunt.
AB  - The Codman-Medos programmable shunt system was designed by Drs. Hakim to relieve
      under and over drainage problems. The system allows for non-invasive post
      implantation adjustment of the opening pressure of the valve through a range of
      30 to 200 mmH2O in 10 mm differentials. However, its wide adjustability does not
      simplify determination of the optimal pressure setting. The bolus injection
      method was used to study the intracranial pressure environment of nine adult
      hydrocephalic patients treated with the Codman-Medos programmable shunt. Changes
      in CSF hydrodynamics with manipulation of the pressure valve setting, and the
      effectiveness of the bolus injection method to determine the optimum valve
      pressure setting were investigated. Initial valve pressure setting at shunt
      implantation was determined on the basis of preoperative CSF dynamics test.
      Another CSF dynamics test was carried out after surgery, and the pressure setting
      was revised in necessary. The new setting was the maximum obtained within normal
      CSF hydrodynamics. If shunt overflow was suspected, pressure was set at a higher
      level. After resetting of the shunt, no patient encountered serious shunt-related
      problems in the follow-up period. This method was considerably useful for
      understanding of the intracranial pressure environment of patients with a
      programmable shunt, and determination of a better shunt setting.

PMID- 9779232
TI  - Evaluation of shunt function in patients who are never better, or better than
      worse after shunt surgery for NPH.
AB  - We investigated the cause of poor outcome in patients with normal pressure
      hydrocephalus (NPH) who did not respond as expected after shunt surgery. Two
      methods were used to evaluate shunts: radionuclide shunt patency study, or
      continuous ICP monitoring. 33/52 shunted patients (64%) from 1989 to 1995 had
      poor outcome, and 28/52 (54%) were investigated. Of those investigated, 9/28
      (32%) were never better, and 19/28 (68%) were initially better then worse. Of 9
      patients who were never better, ineffective shunt function was seen in 7; 5 had
      shunt revision (2 declined), and 1 improved. Of 19 patients who were initially
      better then worse, 15 had ineffective shunts; 15 underwent shunt revision, and 13
      improved. Poor clinical outcome occurred in two-thirds of all patients after
      shunt surgery for NPH, but a potentially treatable cause (i.e. obstruction of the
      shunt or a shunt system that was patent but did not adequately correct the CSF
      circulatory disorder) was found in nearly 80% (22/28) of those investigated. The
      predominant cause of ineffective shunt function was obstruction of the peritoneal
      catheter. Clinical recovery occurred in 70% (14/20) of patients who had shunt
      revision surgery. We conclude that ineffective shunt function is a frequent cause
      of poor outcome after shunt surgery to treat NPH that should be sought and
      treated. These results have implications for longitudinal studies of the
      diagnosis and treatment of NPH. The effect of unrecognized shunt ineffectiveness
      on prior studies is unknown. Future studies should be designed to confirm that
      shunts are functioning before the diagnosis of NPH is considered incorrect.

PMID- 9779233
TI  - Differential diagnosis of NPH and brain atrophy assessed by measurement of
      intracranial and ventricular CSF volume with 3D FASE MRI.
AB  - Differential diagnosis of NPH and brain atrophy is sometimes difficult. Recently,
      a new method using MRI was introduced as a noninvasive, direct technique for the
      measurement of intracranial CSF volume. Using this new technique, we measured the
      intracranial and ventricle CSF volume in patients with enlarged ventricles in
      order to differentiate between NPH and brain atrophy. Ten healthy volunteers
      (control group) and 21 patients with enlarged ventricles were enrolled in this
      study. Eleven out of 21 patients were clinically diagnosed as having NPH (shunted
      group) and the remaining 10 patients were considered to have cerebral atrophy
      (non-shunted group). Intracranial and ventricular CSF volume in each case were
      measured by 3D FASE (Fast Asymmetric Spine-Echo) MR imaging sequence with region
      growing method. Ventricular/intracranial CSF volume ratio was also calculated.
      Ten out of 11 patients showed improvement in clinical symptoms and/or dementia
      scale after shunting. Our results clearly indicate that the ventricular volume in
      the shunted group was enlarged and that the ventricular/intracranial CSF ratio
      was significantly high. Thus we concluded that enlarged ventricle with high
      ventricular/intracranial CSF volume ratio strongly suggests NPH.

PMID- 9779234
TI  - The Belgian Group of Endoscopic Surgery (B.G.E.S.), one of the crown jewels of
      the Royal Belgian Society for Surgery.

PMID- 9779235
TI  - Surgical repair for mitral valve disease.
AB  - The concept of mitral valve repair is discussed emphasizing the basic knowledge
      on which it relies. Analysis of the valve disease, characterization of valvular
      dysfunction and surgical techniques adapted to the most frequent valvular
      dysfunctions are discussed and illustrated.

PMID- 9779236
TI  - Absence of direct relationship between intraperitoneal cellular influx and
      resistance to experimental peritonitis.
AB  - Intraperitoneal inflammation is an essential defence mechanism against microbial
      invasion of the abdominal cavity. We have recently demonstrated that a single
      contact with heat killed E. Coli or Staphylococcus aureus increased the
      intraabdominal leukocyte influx in rats later challenged by these microorganisms.
      The aim of the present study was to investigate some of the mechanisms of this
      phenomenon and to determine its effect on rats survival in an experimental model
      of peritonitis. The intraabdominal influx of leukocytes following intraperitoneal
      injection of E. coli, Pseudomonas aeruginosa or Staphylococcus was stimulated by
      previous intraperitoneal injection of heat killed microbes. The phenomenon was
      not specific, pretreatment with E. Coli enhanced the intraperitoneal inflammatory
      reaction against Pseudomonas and vice versa. On the contrary, pretreating the
      rats with heat killed microorganisms specifically improved their survival after
      induction of peritonitis with live bacteria, there was no cross-protection. Heat
      killed staphylococcus aureus which stimulated a subsequent inflammatory reaction
      against heat killed E. Coli had no effect on the mortality rates of E. Coli
      peritonitis. In conclusion, there is no direct relationship between resistance to
      peritonitis and the amount of leukocytes migrating into the abdominal cavity.

PMID- 9779237
TI  - Diagnostic and therapeutic approach of dermoid cysts: retrospective study of 30
      cases.
AB  - Dermoid cysts are benign tumours affecting young patients that can derive
      benefits from conservative and minimally invasive surgery. MRI and endovaginal
      sonogram appear to be useful tools in the pre-operative selection for this
      surgery. Tumour markers are definitely indicated for postmenopausal patients
      whereas they appear less useful in young patients. With adequate pre-operative
      selection, both conservative and minimally invasive surgery can be applied with a
      clear benefit for the patient.

PMID- 9779239
TI  - Chylothorax complicating left lower sleeve lobectomy.
AB  - Postoperative chylothorax is an infrequent but potential life-threatening
      complication and has most often been described following oesophageal resection.
      Its incidence after pulmonary resection is low, but has increased to 0.3-0.5%,
      probably due to more extensive types of resections and radical lymph node
      dissections. We report a case of chylothorax after a left sleeve lobectomy for a
      primary bronchogenic carcinoma, that was treated conservatively with chest tube
      drainage and a diet of medium chain triglycerides. Five additional case reports
      in English and French literature confirmed chylothorax after bronchoplastic
      procedures to be extremely rare. More frequent use of bronchial sleeve resection
      as alternative to pneumonectomy to save functional lung tissue, can increase the
      incidence of chylothorax after bronchoplastic procedures.

PMID- 9779238
TI  - Hernia of the diaphragm with gastric volvulus: laparoscopic repair.
AB  - The authors present a case of a diaphragmatic hernia with gastric volvulus, 29
      months after a left thoracophrenolaparotomy. The surgical repair was performed by
      laparoscopy. The authors discuss the laparoscopic approach in the treatment of
      diaphragmatic disorders.

PMID- 9779240
TI  - Cardiac hydatid cyst in left ventricle.
AB  - Hydatid cyst of the heart is an uncommon lesion which usually develops in the
      left ventricle. A 34-year-old patient with hydatid cyst of the left ventricle,
      who was operated under cardiopulmonary bypass, is presented. Postoperative course
      at one year was uncomplicated.

PMID- 9779241
TI  - Acute compartment syndrome.
AB  - Acute compartment syndrome is a serious complication of injury. It occurs when
      raised pressure within a closed osteofascial compartment compromises the
      circulation and function of tissues within the compartment. Most cases are caused
      by fracture. The largest group are tibial diaphyseal fractures, followed by soft
      tissue injury, crush syndrome, distal radial fractures and forearm diaphyseal
      fractures. Those at risk of developing acute compartment syndrome are young
      males, patients with bleeding disorders or on anticoagulant therapy and in the
      upper limb, high energy injury. The clinical symptoms and signs of acute
      compartment syndrome are pain, stretch pain and neurological abnormality, none of
      which are constantly present. Since early diagnosis of this condition is of
      paramount importance compartment monitoring is recommended. The recommended
      tissue pressure threshold for decompression has been variable through the years
      but should be related to the patient's blood pressure. A difference of less than
      30 mmHg between the diastolic and tissue pressures has been validated clinically
      and it is recommended that at this level serious consideration should be given to
      decompression of the affected compartments. Use of this pressure threshold with
      compartment monitoring has been shown to half the delay to fasciotomy and
      significantly reduces the late complications of acute compartment syndrome.

PMID- 9779242
TI  - The pathophysiology of the acute compartment syndrome.
AB  - The acute compartment syndrome is a condition in which increased pressure within
      a limited space compromises the circulation and function of the tissues therein,
      resulting in tissue ischaemia, necrosis and nerve damage. This rise in tissue
      pressure originates in a decrease of the compartment size or increase of the
      intracompartmental volume by oedema and/or haemorrhage. Following the arterio
      venous gradient theory, capillary blood flow may be impaired through increased
      venous pressure, decreased arterial pressure and increased peripheral vascular
      resistance. Often, compartment syndromes develop during reperfusion following a
      period of ischaemia. During ischaemia, there is a gradual depletion of
      intracellular stores of high energy phosphate bonds and glycogen stores. There is
      a buildup of products of glycolysis, particularly lactic acid, with accompanying
      hydrogen ion accumulation as well as an increase in intracellular reducing
      agents. Reperfusion may, instead of restoring normal muscle metabolic activity,
      cause harmful effects by washing out necessary precursors for adenine nucleotide
      resynthesis. Production of oxygen free radicals occurs with ensuing lipid
      peroxidation, and calcium influx occurs upon reoxygenation with resultant
      disruption of oxidative rephosphorylation in the mitochondria. Furthermore,
      several lines of evidence suggest that white blood cells are important in the
      pathogenesis of reperfusion injury. Upregulation of both neutrophil receptors and
      endothelial leucocyte adhesion molecules leads to the sequestration of white
      blood cells in the muscle with prolongation of the reperfusion injury. This
      subsequently results in damage to remote organs such as lungs, liver, heart and
      kidneys.

PMID- 9779244
TI  - Fasciotomies of the limbs: how to do it?
AB  - The compartment syndrome has been defined as an elevation of the interstitial
      pressure in a closed osteofascial compartment resulting in microvascular
      compromise. The only effective treatment is early decompression of the involved
      compartment. In acute conditions, this decompression can only be established if
      skin and fascia are incised over the muscular part of the compartment. A good
      knowledge of the anatomy and importance of the fascia generalis, communis and
      propria is necessary for successful and complete decompression. Classic and more
      recent anatomical and clinical data are selected from the surgical literature to
      provide comprehensive and anatomically based guidelines for fasciotomies of the
      upper and lower limbs.

PMID- 9779243
TI  - Local and systemic consequences of severe ischemia and reperfusion of the
      skeletal muscle. Physiopathology and prevention.
AB  - Revascularization of a limb after a severe and prolonged period of ischemia may
      be associated with high rates of mortality and amputation, because of the
      development of a postrevascularization syndrome, regardless the cause of
      occlusion (ischemia, trauma, iatrogenic) or the methods used to achieve
      reperfusion (fibrinolysis, surgery, resuscitative therapy). This
      "revascularization" syndrome includes several complications, both local
      (explosive swelling of the limb, compartment syndrome and skeletal muscle
      infarction (rhabdomyolysis) and general (acidosis, hypercalcemia, hypovolaemic
      shock, renal, hepatointestinal and pulmonary failures, arrhythmias and cardiac
      arrest (multiple organ dysfunction). Current therapies are directed against
      complications after they occurred, once revascularization is completed:
      fasciotomy, mannitol and diuretics administration for forced diuresis, fluid
      administration to correct hypovolaemia, use of resins, insulin and glucose or
      haemodialysis to deal with hypercalcemia, administration of buffers (THAM,
      bicarbonate) to correct acidosis, control of hypercalcaemia with orthophosphates
      and calcitonin.... Nevertheless, a substantial percentage of the injury is
      generated upon reperfusion and the muscle may remain viable after prolonged
      period of ischemia. Intra and extraacellular swelling, tissue acidosis, free
      radical mediated damage, loss of adenine nucleotide precursors, and intracellular
      calcium overload have been suggested to be the mechanisms responsible for
      reperfusion injury. Careful control of both the composition and the physical
      conditions of the initial reperfusion (controlled reperfusion) may result, in
      selected cases, in improvements in the metabolism, structure and function of the
      limb after reperfusion.

PMID- 9779245
TI  - Morphological assessment of the effects of cyclosporin A on mast cell--nerve
      relationship in atopic dermatitis.
AB  - There is considerable clinical and experimental evidence that cyclosporin A has
      powerful therapeutic effects on severe, therapy-resistant atopic dermatitis. To
      further clarify the mechanism of beneficial action of cyclosporin A for atopic
      dermatitis, we assessed its effects on mast cell morphology and on the
      topographical relationship between mast cells and cutaneous nerves in lesional
      skin of atopic dermatitis. The ultrastructural features of mast cell-specific
      granules in cyclosporin A-treated skin compared with those in the pretreated skin
      included an increase in the stable granule population and the disappearance of
      signs of granule exocytosis. The close apposition of mast cells to peripheral
      nerve fibres in the upper dermis and an invasion of mast cells into nerve bundles
      in the lower dermis were immunohistochemically noted, and an intimate association
      between mast cells and unmyelinated dermal nerves or Schwann cells was observed
      ultrastructurally in the pretreated lesional skin. After cyclosporin A therapy,
      the close interrelation of mast cells and cutaneous nerves was not seen. These
      findings suggest that cyclosporin A may exert its therapeutic efficacy by
      inhibiting mast cell activation, and by affecting the interaction between mast
      cells and nerves, which may explain the beneficial therapeutic action of
      cyclosporin A in the management of the disease.

PMID- 9779246
TI  - Decreased staining of heparan sulfate in non-lesional skin of a subgroup of
      patients with systemic lupus erythematosus.
AB  - Heparan sulfate proteoglycans (HSPGs) are components of the basement membrane of
      various tissues. They are composed of a core protein and of the negatively
      charged glycosaminoglycan side chain heparan sulfate, which is covalently bound
      to the core protein. We previously found that in both human and murine lupus
      nephritis, heparan sulfate staining in the basement membrane of the glomerulus is
      almost completely absent, and that there was an inverse correlation between
      heparan sulfate staining and glomerular immunoglobulin deposits. As
      immunoglobulin deposits are also present in the skin of systemic lupus
      erythematosus patients, we investigated the heparan sulfate staining pattern in
      the basement membrane of the dermal-epidermal junction. furthermore, we studied
      whether there was a correlation between heparan sulfate staining and deposition
      of immunoglobulin in the basement membrane of this junction, and between heparan
      sulfate staining and the presence of anti-DNA antibodies in the serum. Biopsies
      of non-lesional skin of 21 systemic lupus erythematosus patients (15 anti-DNA
      positive and 6 anti-DNA negative patients at the time of biopsy) were stained for
      the HSPG-core protein (mAb JM-72), highly sulfated stretches within heparan
      sulfate (JM-13), the low sulfated regions of heparan sulfate (mAb JM-403) and for
      immunoglobulin depositions. Abnormal and discontinuous staining of the low
      sulfated parts of heparan sulfate using mAb JM-403 in the basement membrane was
      found in skin biopsies of 4 out of 15 systemic lupus erythematosus patients with
      anti-DNA antibodies. In contrast, all specimens of anti-DNA negative patients
      showed normal continuous staining. Staining with JM-13 and JM-72 showed normal
      linear staining in both groups. The decreased heparan sulfate staining was
      correlated significantly with the presence of immunoglobulin deposits in the
      basement membrane. The subgroup could not be identified by its clinical picture.
      Our results suggest similar but not identical pathways in systemic lupus
      erythematosus nephritis and skin of systemic lupus erythematosus patients.

PMID- 9779247
TI  - Tenascin-C is not a useful marker for disease activity in psoriasis.
AB  - Tenascin-C is an extracellular matrix glycoprotein that is markedly upregulated
      in the dermis of psoriatic skin. In this study, we have addressed the question
      whether the presence of tenascin-C in the lesion or in serum is a marker for
      disease activity. Immunohistochemical staining of tenascin-C before and after
      treatment with different topical and systemic medication showed that tenascin-C
      remained abundant after clinical remission of lesions, indicating that
      downregulation of tenascin-C to normal values is a slow process. By using a
      sensitive enzyme-linked immunosorbent assay to measure levels of serum tenascin-C
      in psoriatic patients and unaffected individuals, we found that tenascin-C levels
      in most patients were within the normal range. Moreover, tenascin-C values did
      not correlate with disease activity. We conclude that tenascin-C is not useful as
      a marker for disease activity in psoriasis.

PMID- 9779248
TI  - Catalase in the stratum corneum of patients with polymorphic light eruption.
AB  - UV radiation generates reactive oxygen species, which may be involved in
      polymorphic light eruption. The endogenous enzymatic defense system includes
      catalase in the epidermis. Thirteen patients with a history of polymorphic light
      eruption, but free from lesions, and 13 controls were investigated from November
      to March. Catalase was analysed in the upper horny layer according to Colin et
      al.'s spectrophotometric technique. In polymorphic light eruption, catalase
      values were about 30% lower than in control subjects. Such deficiency was
      observed in patients free from the disease and not recently sun-exposed. The
      diminished skin catalase in irradiated polymorphic light eruption makes it
      possible that a longer restoration time of catalase is involved in the
      pathogenesis.

PMID- 9779249
TI  - The effects of fibroblast growth factors 1 and 2 on fibre growth of wool
      follicles in culture.
AB  - The effects of fibroblast growth factor-1 (FGF-1) and FGF-2 on fibre growth and
      follicle function were examined using a previously described procedure to culture
      wool follicles. Because the FGFs bind to glycosaminoglycan components of the
      extra-cellular matrix, we also investigated interactions between FGF-1 and FGF-2
      with heparin on wool fibre growth. Individual follicles were microdissected from
      Merino sheepskin and transferred to culture. Follicles increased in length for 6
      days, and in all groups, no significant differences in follicle length were
      observed. Increase in follicle length was associated with fibre growth, follicles
      maintained normal anagen morphology and incorporated [3H]thymidine into the bulb
      and outer root sheath cells. Follicles in all treatments continued to produce
      fibre keratins, as detected by immunohistochemistry. However, the patterns of
      fibre and cytoskeletal proteins incorporating [35S]methionine in control and
      treated follicles were significantly different. We found a considerable decrease
      in the intermediate filament keratins or low sulphur proteins in follicles
      cultured in the presence of FGF-1 and FGF-2 compared to controls. The majority of
      proteins detected in these samples were acidic high sulphur proteins. These
      studies provide evidence for a specific role for the fibroblast growth factors in
      the regulation of fibre differentiation.

PMID- 9779250
TI  - Expression of stratum corneum chymotryptic enzyme in human sebaceous follicles.
AB  - Stratum corneum chymotryptic enzyme (SCCE) may be involved in desquamation, a
      process necessary for maintaining a normal anatomy at all sites where there is
      continuous turnover of cornified epithelia. Using immunohistochemistry and in
      situ hybridization, we have, in this work, analysed SCCE expression in the
      sebaceous follicle. We found expression of SCCE in luminal parts of the pilary
      canal, common sebaceous ducts and proximal sebaceous ducts. In addition, SCCE was
      seen in cells apparently situated within the distal parts of the glandular
      lobules. Co-expression of SCCE and keratin 10 was seen only in the pilary canal
      and the common sebaceous ducts. The results give further support for SCCE being
      involved in desquamation-like processes. The association with cornification seems
      to be more general for SCCE than for keratin 10. The possible role of SCCE in
      diseases involving disturbances in the turnover of cornified cells in the
      sebaceous follicle, such as acne vulgaris, is a question for future studies.

PMID- 9779251
TI  - Cis-urocanic acid down-regulates histamine-mediated activation of adenylate
      cyclase in the pig epidermis.
AB  - Urocanic acid (UCA), one of the skin's major components for absorbing UV
      radiation, is present naturally in the stratum corneum as a trans-isomer. On
      absorption of UVB radiation either in vitro or in the skin, UCA undergoes trans-
      to cis-isomerization in a dose-dependent manner. Although the mechanism by which
      cis-UCA suppresses immunity remains unelucidated, recent studies have indicated
      that cis-UCA appears to inhibit the induction of cyclic AMP in fibroblasts, which
      suggests that this molecule plays an active role in modifications to the skin.
      Here, we report that although neither trans-UCA nor cis-UCA increases cyclic AMP
      in the pig epidermis, cis-UCA actively down-regulates the increase of cyclic AMP
      induced by histamine. The effects of cis-UCA on the pig epidermis are revealed
      through the modulation of the effects caused by histamine. These findings suggest
      that in the pig epidermis, the initial biochemical and cellular event for UVB
      induced immune suppression--that is, the step immediately following the
      isomerization of trans-UCA to cis-UCA--is down-regulation of cyclic AMP brought
      about by the activity of cis-UCA.

PMID- 9779252
TI  - Chilblains and Raynaud phenomenon are usually not a sign of hereditary protein C
      and S deficiencies.
AB  - Hereditary protein C and S deficiencies are risk factors for thrombosis. They are
      associated with purpura fulminans and coumarin-induced skin necrosis. Recently,
      necrotic livedo of the extremities, severe chilblains and severe frostbite have
      been observed in protein C or S deficient patients. Our study was designed to
      evaluate the prevalence of cold-induced acral manifestations in patients with
      protein C or S deficiency. One-hundred-and-six patients with protein C or S
      deficiency and controls matched for sex and age were studied by questionnaire.
      Data included any history of acral manifestation possibly related to cold
      exposure, i.e. chilblains, Raynaud phenomenon, acrocyanosis and possible
      associated factors. Assessment of the diagnosis by a dermatologist was recorded.
      No difference was found in the prevalence of acral manifestations between
      patients and controls. This study suggests that protein C and S deficiencies are
      not risk factors for cold-induced acral manifestations.

PMID- 9779253
TI  - Post-kala-azar dermal leishmaniasis--an unusual presentation.
AB  - Post-kala-azar dermal leishmaniasis can present as hypopigmented macules,
      erythematous to skin-coloured papules, nodules and photosensitive butterfly
      erythema on the face. We present a patient with disseminated annular lesions of
      post-kala-azar dermal leishamaniasis. The patient was treated with daily
      intravenous injections of sodium antimony gluconate for 120 days at a dose of 20
      mg/kg body weight with complete clearance of lesions.

PMID- 9779254
TI  - Systematic cutaneous examination in hepatitis C virus infected patients.
AB  - The purpose of this study was to evaluate the frequency of skin changes among 100
      patients from the Hepatogastroenterology Department of the University Hospital,
      Strasbourg, France who were hepatitis C virus-positive (HCV) and HIV-negative.
      Their clinical data were compared to those of 50 HCV-, and HIV-negative patients
      from the same Department, who suffered from various liver diseases. Psoriasis,
      rosacea, seborrheic dermatitis, cherry angiomas, spider nevus and skin cancers
      were noted in similar proportions in the two groups. In 15% of HCV-positive
      patients vs. 4% of controls, chronic pruritus was noted (p < 0.05). In 9 HCV
      positive patients, pruritus was not related to itching dermatosis, and only 2 of
      these patients had mild cholestasis. Four cases of lichen planus vs. 0 in the
      control group were recorded. The virological data of patients with pruritus or
      lichen planus were not different than those of the rest of the group. Our
      findings indicate that systematic skin check-up in HCV-positive patients is
      valuable.

PMID- 9779255
TI  - Contact allergies in healthcare workers. Results from the IVDK.
AB  - Healthcare workers often suffer from occupational skin disease frequently caused
      by allergic sensitization. Therefore the patch-test results and important patient
      history items of 31,849 patients recorded between 1992 and 1995 in the 24 allergy
      departments participating in the Information Network of Departments of
      Dermatology (IVDK) were evaluated. Significantly increased sensitization rates
      common to the healthcare sector as a whole were found for the vaccine
      preservative thiomersal (12.6% vs. 4.9%), the surface and instrument
      disinfectants glutardialdehyde (9.9% vs. 2.6%), formaldehyde (3.6% vs. 2.1%) and
      glyoxal (4.2% vs. 1.4%), and for the compounds of the thiuram mix (6.7% vs. 2.6%)
      present in protective gloves. Formaldehyde seems to lose its importance, but
      glyoxal must be added to the list of occupational allergens in the healthcare
      sector. In addition, occupation-specific sensitization was observed, with
      fragrances in massage therapists (16.1% vs. 10.6%) and nurses (13.8% vs. 11.4%),
      as well as with methacrylates in dental technicians. The often assumed importance
      of drugs as type-IV allergens was not confirmed, at least in terms of quantity.
      The identification of subgroups of increased risk and of occupation-specific
      allergens could be the basis of targeted preventive action in the healthcare
      sector.

PMID- 9779256
TI  - The quantification of patch test responses: a comparison between echographic and
      colorimetric methods.
AB  - Patch testing is widely used both for clinical and experimental purposes.
      Although the clinical grading employed routinely is of practical value, the lack
      of objectivity makes it unsuitable for research purposes and dose-response
      analysis studies. Instrumental measuring techniques have been applied to patch
      test evaluation, because they enable objective quantification of different
      biophysical aspects of the inflammatory reaction by means of a continuous
      assessment scale, providing data suitable for statistical analysis. In order to
      compare the colorimetric and echographic methods for the evaluation of reactions
      of different intensity, we performed patch tests with 5% nickel sulfate on the
      flexor aspect of the forearm in 120 nickel-sensitive patients. Clinical and
      instrumental measurements were performed at 72 h. Numerical values corresponding
      to instrumental measurements were compared to the positivity degree, as assessed
      clinically. Whereas echographic parameters, expressing the intensity of oedema
      and inflammatory infiltration, enabled a distinction between +, +2 and +3
      reactions, colorimetric a* values, describing erythema, failed to distinguish
      between +2 and +3 reactions. Thus, the use of ultrasound is advisable for the
      quantification of skin reactions of great intensity, whereas the colorimetric
      method could be usefully employed for dose-response studies assessing minimal
      eliciting concentrations of allergens, and for the evaluation of clinically
      undetectable reactions.

PMID- 9779257
TI  - The significance of previous contact dermatitis for elicitation of contact
      allergy to nickel.
AB  - In 2 earlier studies, we found increased nickel re-test reactivity at earlier
      experimentally induced nickel eczema sites. The aim of this study was to
      investigate if earlier contact dermatitis caused by another allergen or earlier
      irritant contact dermatitis also influenced the reactivity when nickel was
      applied topically on earlier but healed dermatitis sites. Twenty-three females
      with contact allergy to both nickel and cobalt were involved in the study.
      Experimental contact dermatitis from nickel, cobalt and SLS was induced on the
      lower back. One month later, challenge patch testing with a serial dilution of
      nickel on the previous but healed dermatitis sites, and on a control area, was
      done. The tests were read blindly. Significantly higher test reactivity was found
      at the site with previous allergic contact dermatitis from nickel, and
      significantly lower test reactivity was observed at the previous SLS dermatitis
      site.

PMID- 9779258
TI  - Prevalence of self-reported hand dermatosis in upper secondary school pupils.
AB  - The purpose of the present study was to estimate the prevalence of self-reported
      hand dermatosis among upper secondary school pupils. All pupils in grades 1 and 3
      from the four upper secondary schools in Vaxjo, southern Sweden, were invited to
      participate in the study. A previously validated questionnaire was used. Of the
      2609 invited pupils, 2572 (98.6%) responded to the questionnaire. The point
      prevalence of self-reported hand dermatosis was 4.2% (95% CI, 3.4-4.9%) with no
      significant differences between gender and grades. The overall one-year
      prevalence of self-reported hand dermatosis was 10.0% (95% CI, 8.8-11.1%), i.e.
      the corresponding figures for males were 7.3% (95% CI, 5.9-8.8%) and for females
      12.5% (95% CI, 10.6-14.6%). There were significant gender differences in grade 1
      (p < 0.001) and in grade 3 (p < 0.05). Males and females from the hotel and
      restaurant course had the highest one-year prevalence in grade 3. It is concluded
      that the high point and one-year prevalence of hand dermatosis among upper
      secondary school pupils merits long-term prospective study in order to address
      the question of which aetiological or trigger factors are most important in the
      development of hand dermatosis in a population.

PMID- 9779259
TI  - Kimura's disease associated with ulcerative colitis: detection of IL-5 mRNA
      expression of peripheral blood mononuclear cells and colon lesion.
AB  - Kimura's disease is considered to be a Th2 type allergic reaction based on the
      presence of eosinophilia and IgE hyperimmunoglobulinemia. We report a 26-year-old
      Japanese male with this disorder associated with ulcerative colitis. IL-5 is a
      selective stimulator for the production of eosinophilia and is considered to play
      an important role in Kimura's disease. IL-5 mRNA from peripheral blood
      mononuclear cells and the colon lesion were detected by the reverse-transcriptase
      polymerase chain reaction method, indicating that IL-5 can also be of importance
      in ulcerative colitis.

PMID- 9779260
TI  - Naevi spili, Cafe-au-lait spots and melanocytic naevi aggregated alongside
      Blaschko's lines, with a review of segmental melanocytic lesions.
AB  - This is the first case in the literature describing naevi spili, cafe-au-lait
      spots and melanocytic naevi aggregated along-side Blaschko's lines. The pattern
      of melanocytic lesions in our patient is different from the congenital pigmentary
      syndromes and the segmental distribution of melanocytic naevi, the quadrant
      distribution of dysplastic naevi or the partial unilateral lentiginosis which
      here are shortly reviewed. The distribution may be a result of a somatic mutation
      occurring at an early stage of embryogenesis when neural structures had already
      been formed.

PMID- 9779261
TI  - Sporotrichoid tuberculoid leprosy.

PMID- 9779262
TI  - Familial acne keloidalis.

PMID- 9779264
TI  - Higher incidence of rolled hairs in renal transplant recipients: a possible
      complication of corticosteroid and cyclosporine therapy.

PMID- 9779263
TI  - Acute generalized exanthematous pustulosis upon ingestion of a progesterone
      preparation.

PMID- 9779265
TI  - Comparison of betamethasone valerate solution with phototherapy (UVB comb) in
      scalp psoriasis treatment.

PMID- 9779266
TI  - A follicular lichenoid eruption as manifestation of chronic graft-vs-host
      disease.

PMID- 9779267
TI  - The number of diagnostic features in patients with atopic dermatitis correlates
      with dryness severity.

PMID- 9779268
TI  - Treatment of acne vulgaris with colchicine.

PMID- 9779269
TI  - CO2 laser eradication of recalcitrant condyloma acuminatum does not influence T
      lymphocyte subsets.

PMID- 9779270
TI  - The so-called striated muscle hamartoma is a hamartoma of cutaneous adnexa and
      mesenchyme, but not of striated muscle.

PMID- 9779271
TI  - Adnexal polyp of neonatal skin observed beyond the neonatal period.

PMID- 9779272
TI  - Erythema multiforme combined with legionellosis.

PMID- 9779273
TI  - Severe drug-induced pneumonitis associated with minocycline and nicotinamide
      therapy of a bullous pemphigoid.

PMID- 9779274
TI  - Delayed pressure urticaria causing obstruction of urinary flow.

PMID- 9779275
TI  - Chronic urticaria and IgA myeloma.

PMID- 9779276
TI  - The anti-BRCA1 peptide antibody C-20 recognizes smooth muscle cells.

PMID- 9779277
TI  - A case of pigmented purpuric eruption associated with hereditary spherocytosis.

PMID- 9779278
TI  - Lichen amyloidosis in an HIV-infected Patient. A case report and review of the
      literature.

PMID- 9779279
TI  - Evaluation of a sexual abuse prevention program for female Chinese adolescents
      with mild mental retardation.
AB  - The effectiveness of the Behavioral Skills Training program in the primary
      prevention of sexual abuse for 72 female Chinese adolescents with mild mental
      retardation was evaluated. Subjects were assigned to either the Behavior Skills
      Training program or an attention control program. The Behavioral Skills Training
      group demonstrated greater knowledge regarding sexual abuse and self-protection
      skills at posttest, which was maintained at 2-month follow-up, though the scores
      on the recognition of appropriate-touch requests showed a decreasing trend. They
      also exhibited less fear of objects, people, and situations after the prevention
      program. Booster sessions and a longer program duration should result in better
      retention. Results suggest that a modified Behavior Skill Training program can be
      effective with Chinese adolescents with mental retardation.

PMID- 9779280
TI  - Parents' developmental expectations and child characteristics: longitudinal study
      of children with developmental delays and their families.
AB  - The relation between child characteristics and parents' developmental
      expectations for their children with developmental delays at ages 3, 7, and 11
      was examined. Parents' developmental expectations were moderately stable over
      time, tending to decline as children matured. As hypothesized, parents'
      developmental expectations were associated with child characteristics at age 3
      and became increasingly correlated with child characteristics over time. Results
      of regression analyses generally support the hypothesis that early child
      characteristics, but not early parent expectations, are the best predictors of
      parents' developmental expectations and child outcomes at child age 11. The one
      exception was the prediction of children's daily living competence by a
      combination of early parent expectations and children's Gesell DQ scores.

PMID- 9779281
TI  - Dementia in adults with Down syndrome: diagnostic challenges.
AB  - Although dementia associated with Down syndrome is often presumed to be
      progressive and irreversible, variations in disease course have been described.
      In addition, prevalence rates have varied widely among studies. This interim
      report is a description of the status of 70 adults with Down syndrome who are
      being followed for signs of dementia. Of the 70, 12 met all criteria for
      dementia, 40 met subsets of criteria, and 18 met no criteria. Information is
      provided on instruments used, rationale for choice and revision of instruments as
      well as criteria used to identify dementia and changes in the status of the
      participants. The results suggest that extreme care is needed when diagnosing
      dementia in adults with Down syndrome, for both clinical and research purposes.

PMID- 9779282
TI  - Empirically based methods to assess the preferences of individuals with severe
      disabilities.
AB  - A literature review was conducted to provide a synthesis of 18 years of research
      on preference assessment with individuals who have severe disabilities (e.g.,
      severe mental retardation, autism, multiple disabilities). Through this
      synthesis, several procedural variables were identified that may influence the
      outcome of preference assessment, including context, assessment stimuli,
      selection response, and format. Recommendations were given for designing
      preference assessment, and questions were raised for future research.

PMID- 9779283
TI  - Relation of attributional beliefs to memory strategy use in children and
      adolescents with mental retardation.
AB  - Attributional beliefs of African American 11- and 17-year-old students with
      mental retardation were assessed with an open-ended interview and the Students'
      Perception of Control Questionnaire. Results from the questionnaire indicated
      that strategy ratings were intercorrelated as were capacity ratings. Yet, the
      constructs of strategy and capacity were differentiated by both age groups.
      Beliefs in the importance of internal strategies were positively related to
      recall and strategy use, and beliefs in the importance of external strategies
      were negatively related to memory strategy use and recall. Findings suggest that
      attributional beliefs vary among students with mental retardation and have the
      potential to either energize or inhibit achievement-related behavior.

PMID- 9779284
TI  - Assessing social integration in employment settings: current knowledge and future
      directions.
AB  - Based on a review of descriptive studies found in the employment literature from
      1985 through 1995, we classified empirical measures that have been used to assess
      the social integration of employees with disabilities. In addition, we aggregated
      findings that described social interaction patterns in employment and summarized
      similarities and differences between the interactions of employees with and
      without disabilities. Ten categories of measures of social interaction were
      identified, and occurrence of social interaction was found to vary by
      environmental context and presence of disability. Findings were then compared to
      those of social skills interventions conducted in the workplace. Although
      aggregated findings revealed important information about social integration in
      work settings, critical gaps were found in current knowledge bases.

PMID- 9779285
TI  - Conditional versus trial-unique delayed matching-to-sample.
AB  - We compared performance on conditional and trial-unique delayed identity matching
      to-sample procedures. In Experiment 1, participants with moderate to severe
      mental retardation were exposed to both procedures under a single, brief delay
      value. Three of 5 subjects showed higher accuracy in the trial-unique sessions.
      In Experiment 2, participants with mild mental retardation were exposed to delay
      values of 0, 2, 4, 8, and 16 seconds, randomized within each session. For 3 of 4
      subjects, accuracy was highest with trial-unique, and lowest on the conditional
      matching-to-sample, at longer delays. Across the two studies, 6 of 9 subjects
      showed lower delayed matching accuracy when fewer rather than more stimuli were
      included in a session.

PMID- 9779286
TI  - Cognitive decline in Down syndrome: a validity/reliability study of the test for
      severe impairment.
AB  - The utility of the Test for Severe Impairment was studied with 60 older persons
      who had Down syndrome. Construct validity, test-retest reliability, and
      interrater reliability were established for the full study group and for
      subgroups based on degree of mental retardation and dementia status. There was no
      difference in scores by gender. There were some interesting findings for the
      group with moderate mental retardation and dementia and the group with severe
      mental retardation without dementia that may signal specific applications and
      limitations of the test for use with individuals who have Down syndrome. The
      internal consistency of the instrument was satisfactory. Results suggest that
      this test is a useful performance-based task for persons with Down syndrome.

PMID- 9779287
TI  - My association with Ludwik Hirszfeld, Wroclaw 1945-1954.

PMID- 9779288
TI  - Human natural killer cells.
AB  - Human natural killer (NK) cells comprise 10 to 15% of peripheral blood
      lymphocytes, characterized by their morphologic appearance of large granular
      lymphocytes (LGLs) and phenotype CD3- CD56+ CD16+ or CD16-. Functionally, these
      cells are defined by their ability to lyse target cells without prior
      sensitization and without restriction by major histocompatibility (MHC) antigens.
      These cells play an important role in immune defenses, especially after
      hematopoietic transplantation. They contribute to the defenses against virus
      infected cells, graft rejection, and neoplasias; they also participate in the
      regulation of hematopoiesis through cytokine production and cell to cell
      interaction. In this mini-review we attempt to summarize the most relevant
      findings about these cells in terms of their origin and differentiation, their
      cell surface characteristics including activation and their cytolytic pathways.
      We have also provided a brief approach of their potential clinical use. Increased
      knowledge of NK cell differentiation, ontogeny and regulatory mechanisms may be
      of use for the planning of immunotherapeutic strategies.

PMID- 9779289
TI  - Immunoregulatory effects of a nutritional preparation containing bovine
      lactoferrin taken orally by healthy individuals.
AB  - The aim of this study was to monitor several immune parameters in 17 healthy
      volunteers taking orally commercially available capsules containing bovine
      lactoferrin (BLFT) for 10 days (40 mg of BLFT daily). We determined leukocyte
      number and content of main blood cell types, spontaneous and phytohemagglutinin A
      (PHA)-induced proliferation of lymphocytes, plasma levels of interleukin 6 (IL-6)
      and tumor necrosis factor alpha (TNF-alpha) as well as spontaneous and
      lipopolysaccharide (LPS)-induced production of these cytokines in peripheral
      blood cell cultures. All measurements were performed before, one day and 14 days
      following cessation of BLFT treatment. We established some, transient drop in the
      percentage of neutrophils accompanied by an opposite phenomenon with regard to
      lymphocyte levels. More profound changes were registered in the percentage of
      other cell types, for example a 100% increase in the level of immature cell forms
      (bands) was noted. At the same time the percentages of eosinophils and monocytes
      declined significantly. All these changes were, however, more individual and
      regulatory, the direction of these changes depended on initial picture of blood
      cells. Although the proliferative response of lymphocytes showed, on average, a
      transient decrease, differentiated effects of BLFT treatment were observed
      depending on initial ability of lymphocytes to proliferate. TNF-alpha serum
      levels showed a tendency to decrease during the monitoring time, the changes of
      IL-6 levels were, however, not significant. As in the case of the proliferative
      response, the treatment with BLFT was regulatory with respect to serum TNF-alpha
      levels. When we analyzed spontaneous and LPS-induced cytokine production in cell
      cultures we found that mainly the mean spontaneous response was affected
      (inhibition). We also observed a typical, regulatory action of BLFT on the level
      of spontaneously produced IL-6. This kind of regulatory action of BLFT was also
      found in the case of spontaneously produced TNF-alpha in cell cultures. The
      influence of other ingredients such as selenium or vitamins, contained in the
      capsules, cannot be excluded, although our latest data showed that orally taken
      bovine lactoferrin alone can induce identical changes as BLFT. Taken together, we
      revealed regulatory effects of oral treatment with commercially available
      capsules, containing BLFT. The results indicate that oral administration on BLFT
      containing capsules may regulate some immune parameters in healthy individuals.
      In addition, the data suggest that bovine lactoferrin may be applied in clinic to
      improve the immune status of patients.

PMID- 9779290
TI  - Does moxonidine increase cytotoxic activity of ethanol in rats? Preliminary
      report on the base of the ultrastructural study.
AB  - Combined effects of moxonidine and ethanol on ultrastructure of selected Wistar
      Kyoto rat organs (kidney, liver, heart) were investigated. In cells of the
      animals, which received moxonidine alone, no morphological changes were found. In
      the group of rats which received alcohol, several typical submicroscopical
      changes were found, especially related to the mitochondria. After the combined
      administration of ethanol and moxonidine the pathological changes were bigger
      than those found in animals which received alcohol alone. Those changes were
      particularly significant in kidney and liver. The results might indicate that
      moxonidine increased cytotoxic activity of ethanol on several organs in rats.

PMID- 9779291
TI  - Epithelial-mesenchymal cell interactions and participation of the neuroendocrine
      markers in tumor development. Immunohistochemical study.
AB  - Existence of the organ stem cell population seems to decide on ability of the
      tissue to regenerate and, likewise, on carcinogenesis. The source of the organ
      specific stem cells may be perivascular mesenchyma of thin-walled vascular
      channels. Our previous study on the breast cancer indicates that the perivascular
      mesenchyma of thin-walled vessels appears to be source of myoid cells
      (myofibroblasts) from which cancer cells arise. Similar results have been
      observed in the cancers of lung, salivary gland and colon, investigated in the
      current study. The perivascular cells of thin-walled channels are the source of
      myoid cells with expression of synaptophysin (Syn) and/or chromogranin A (Chg A),
      and from these cells neoplastic cells could originate. Syn and/or Chg A positive
      neoplastic cells were particularly well visible in connection with the vascular
      channels on the peripheries of tumors while other parts of tumors were only weak
      positive or negative for those neuroendocrine markers. Similarly as in breast
      cancers, the S100-protein positive dendritic cells with various of distribution
      were seen, expressing intimate connection with neoplastic cells. The epithelial
      pearls especially abundant in non-small cell lung carcinomas demonstrated
      immunohistochemical analogy to Hassall's bodies: they had monocytogenic cell
      inside and they displayed thymosin alpha 1 (TA1), as well as mucin secretion and
      minute calcification. Some epithelial cells expressed desmin and Syn. All types
      of investigated cancers demonstrated TA1. Results of our present study suggest
      that the perivascular cells have a differentiation defect. Such defect may
      initiate abnormal stromal environment, commonly observed in neogenesis, however,
      the presence of thymic growth factors may favor tumor growth.

PMID- 9779292
TI  - Myoid cells and neuroendocrine markers in myasthenic thymuses.
AB  - We have studied myoid cells in normal and myasthenic thymuses as well as in
      thymomas. For the presence of neuroendocrine markers-producing cells and
      identification of synaptophysin (Syn) the immunohistochemical method and
      immunoblot analysis were used. Myoid cells can be demonstrated in the thymus of
      myasthenic patients in high number. These cells occur in the vicinity of
      Hassall's bodies but also within them. Some regenerated Hassall's bodies
      displayed majority of myoid cells with their concentric arrangement around the
      centrally situated lacunar-like cell with nuclei of monocytogenic origin. Such
      phenomenon may suggest cooperation of myoid cells and their epithelial
      transitional forms with monocytogenic cells in various thymic hormone production.
      It is likely that myoid cells are the source of some thymic epithelial cells.
      According to some authors, thymomatous epithelial cells and skeletal muscle share
      a common epitope defined by a monoclonal antibody (mAb), whereas thymic
      epithelial cells possess acetylocholine receptor (AChR) on their surface. The
      epithelial cells of some thymomas express also desmin. In normal thymuses of
      children, Syn and chromogranin A (Chg A) were demonstrated in some cells of
      Hassall's bodies by immunohistochemical method. In addition, antibodies to Syn
      stained nerve structures surrounding the thymic blood vessels. In myasthenic
      thymuses, Syn expression was in cortical and medullary epithelial cells, in myoid
      cells and only scanty and focal in keratinized epithelial cells of Hassall's
      bodies. The epithelial cells of some thymomas also express Syn. In some thymuses
      of all groups investigated in this study Chg A was seen in single cells of
      Hassall's bodies and focally in cortical epithelial cells. Our results show that
      in normal thymuses of cardiac surgery patients and in the adult myasthenic
      thymuses antibody raised against Syn recognized protein with molecular weight of
      48,000 but not normal (38,000) Syn. It remains to be elucidated if the
      overexpression of synaptophysin-like protein in myasthenic thymuses is a
      compensatory phenomenon to the defect in normal synaptic function.

PMID- 9779293
TI  - Insertion of the IL-2 gene decreases tumorigenicity of murine fibrosarcoma.
AB  - Murine interleukin 2 (mIL-2) cDNA was introduced through lipofection into cells
      of murine F-69-3 fibrosarcoma line established in vitro from tumors induced
      chemically in athymic mice. Using a modified MTT bioassay in CTLL-2 indicator
      line the F-69-3/IL-2 transfectants were found to secrete between 650-1750
      laboratory units (LU) of IL-2/5 x 10(5) cells/48 h in restricted culture
      conditions. When inoculated subcutaneously to immunocompetent BALB/c or CD2F1
      mice, the transfected cells showed reduced tumorigenic potential as compared with
      parental F-69-3/wt or control F-69-3/neo cells. The rejection of F-69-3/IL-2
      tumors required an intact immune system as they grew progressively in athymic
      mice. The majority of immunocompetent mice that rejected IL-2 secretors were
      found to be protected against subsequent challenge with parental cells. These
      preliminary results suggest that IL-2-transfected murine fibrosarcoma could be
      used as a model for studying mechanisms underlying the antitumor immune response.

PMID- 9779295
TI  - TENNET VIII: Theoretical and experimental neuropsychology. Montreal, Quebec,
      Canada. June 16-18, 1997. Abstracts.

PMID- 9779294
TI  - Sequence, structural, functional, and phylogenetic analyses of three glycosidase
      families.
AB  - Glycosidases, which cleave the glycosidic bond between a carbohydrate and another
      moiety, have been classified into over 63 families. Here, a variety of
      computational techniques have been employed to examine three families important
      in normal and abnormal pathology with the aim of developing a framework for
      future homology modeling, experimental and other studies. Family 1 includes
      bacterial and archaeal enzymes as well as lactase phlorizin-hydrolase and klotho,
      glycosidases implicated in disaccharide intolerance II and aging respectively. A
      statistical model, a hidden Markov model (HMM), for the family 1 glycosidase
      domain was trained and used as the basis for comparative examination of the
      conserved and variable sequence and structural features as well as the
      phylogenetic relationships between family members. Although the structures of
      four family 1 glycosidases have been determined, this is the first comparative
      examination of all these enzymes. Aspects that are unique to specific members or
      subfamilies (substrate binding loops) as well those common to all members (a
      beta/alpha)8 barrel fold) have been defined. Active site residues in some domains
      in klotho and lactase-phlorizin hydrolases differ from other members and in one
      instance may bind but not cleave substrate. The four invariant and most highly
      conserved residues are not residues implicated in catalysis and/or substrate
      binding. Of these, a histidine may be involved in transition state stabilization.
      Glucosylceramidase (family 30) and galactosylceramidase (family 59) are mutated
      in the lysosomal storage disorders Gaucher disease and Krabbe disease,
      respectively. HMM-based analysis, structure prediction studies and examination of
      disease mutations reveal a glycosidase domain common to these two families that
      also occurs in some bacterial glycosidases. Similarities in the reactions
      catalyzed by families 30 and 59 are reflected in the presence of a structurally
      and functionally related (beta/alpha)8 barrel fold related to that in family 1.

PMID- 9779296
TI  - Minocycline and autoimmunity.

PMID- 9779297
TI  - Nitric oxide in systemic sclerosis lung: controversies and expectations.

PMID- 9779298
TI  - Anti-endothelial cell antibodies in systemic sclerosis: significant association
      with vascular involvement and alveolo-capillary impairment.
AB  - OBJECTIVE: To assess the frequency of antiendothelial cell autoantibodies (AECAs)
      in a group of patients with systemic sclerosis (SSc) and possible associations
      with clinical and serologic features of the disease. METHODS: Sera from 50
      patients with SSc (38 with the limited and 12 with the diffuse form) were
      screened for AECA (ELISA). The reference limits were were 56.6% for the IgM
      isotype and 3.3.5% for the IgG isotype. AECA results were analyzed in relation to
      lung involvement (chest x-ray, high resolution computed tomography (HRCT),
      ventilation scintiscan with radioaereosol (DTPA), pulmonary pressure (echodoppler
      technique): heart involvement (EKG, 24 hr ambulatory EKG, echocardiography),
      cutaneous involvement (skin score), capillaroscopic characteristics and digital
      ulcers. AECA were also correlated with the erythrocyte sedimentation rate (ESR),
      anticentromere (ACA) and antitopoisomerase I (ATA) autoantibodies, and
      angiotensin converting enzyme plasma levels (ACE). RESULTS: The AECA IgG
      prevalence was 40% (22/50) for the SSc group as a whole, without significant
      differences between subsets. A significant negative correlation was shown between
      the AECA and ACE plasma levels in both subsets. In the diffuse form, a
      significant positive correlation was found between AECA and ESR and significant
      associations were found between AECA and the parameters reflecting alveolo
      capillary involvement (DLco, DTPA), the pulmonary artery pressures, digital
      ulcers and capillaroscopic abnormalities. No statistically significant
      correlations were found between AECA and heart involvement, the skin score or
      pulmonary interstitial fibrosis. CONCLUSIONS: These data suggest that in SSc the
      anti-endothelial cell antibodies are directly linked to vascular injury and could
      reflect endothelial damage. Further studies are needed to verify whether AECA
      might identify a subgroup of patients at higher risk for the development of
      vascular crises and whether they might therefore be considered a predictor of
      outcome in SSc patients.

PMID- 9779299
TI  - Serum matrix metalloproteinase-3 and fibrin degradation product levels correlate
      with clinical disease activity in rheumatoid arthritis.
AB  - OBJECTIVE: Plasmin and matrix metalloproteinase-3 (MMP-3) have been linked to
      articular destruction in rheumatoid arthritis (RA). We compared circulating
      levels of plasmin-mediated fibrin degradation product (FDP D-dimer) and MMP-3
      with traditional parameters of disease activity in RA to determine their clinical
      utility. MATERIALS AND METHODS: Serum levels of MMP-3 and D-dimer were determined
      by enzyme-linked immunoassays in 60 patients with RA. Twenty healthy females and
      21 patients with systemic lupus erythematosus (SLE) served as controls. RESULTS:
      MMP-3 (436.8 +/- 474.2 ng/ml) and D-dimer levels (351.2 +/- 296.3 ng/ml) were
      markedly elevated in the sera from RA patients as compared with healthy controls
      (43.9 +/- 15.2 ng/ml and 63.0 +/- 64.1 ng/ml, p < 0.0001, respectively). Both
      levels strongly correlated with each other (r = 0.627, p < 0.0001) and were
      closely associated with various clinical parameters for the disease activity of
      RA, including the erythrocyte sedimentation rate (ESR) and the Lansbury's
      activity index (p < 0.0001). MMP-3 levels were more highly correlated with
      articular parameters such as the swollen and painful joint counts (r = 0.454, p =
      0.0002), whereas D-dimer levels correlated well with C-reactive protein (CRP)
      levels (r = 0.581, p < 0.0001). In SLE patients, MMP-3 (239.1 +/- 199.6 ng/ml, p
      < 0.0001) and D-dimer levels (86.9 +/- 85.2 ng/ml, p = 0.0278) were also higher
      than in healthy controls. Both levels correlated with each other (r = 0.612, p =
      0.0025), and were associated with ESR and CRP levels, as was observed in RA
      patients, but not with most of the other clinical indicators for SLE.
      CONCLUSIONS: Serum levels of MMP-3 and D-dimer are clinically useful indicators
      for disease activity in RA. Our results further support the hypothesis that MMP-3
      and plasmin may interact in the inflammatory synovial tissues, and thus augment
      the articular destruction seen in RA. In SLE patients, however, MMP-3 producing
      cells could be different from in RA patients, and further studies will be
      required to clarify the pathogenetic mechanism underlying the raised serum levels
      of MMP-3 and/or D-dimer.

PMID- 9779300
TI  - Anti-neutrophil cytoplasmic antibodies in 566 European patients with systemic
      lupus erythematosus: prevalence, clinical associations and correlation with other
      autoantibodies. European Concerted Action on the Immunogenetics of SLE.
AB  - OBJECTIVES: To evaluate, in a cohort of 566 patients with systemic lupus
      erythematosus (SLE) drawn from 11 European centres: (i) the prevalence of ANCAs
      and their subspecificities in a large series of European SLE patients; (ii) the
      possible associations of ANCA with the most common clinical manifestations of the
      disease; and (iii) whether ANCAs correlate with some of the autoantibodies
      commonly found in SLE. METHODS: ANCA detection was performed by indirect
      immunofluorescence (IIF), and by ELISA for lactoferrin (LF), myeloperoxydase
      (MPO), proteinase3 (PR3) and lysozyme (LZ) subspecificities. RESULTS: The
      prevalence of ANCA was 16.4% (IIF). The prevalence of LF was 14.3%, LZ 4.6%, MPO
      9.3%, and PR3 1.7%. Our results show that ANCA is associated with certain
      clinical manifestations of SLE. In particular, positive correlations were found
      between IIF ANCA and serositis (p = 0.026), livedo reticularis (p = 0.01), venous
      thrombosis (p = 0.03) and arthritis (p = 0.04), while anti-LF antibodies were
      associated with serositis (p = 0.05) and livedo reticularis (p < 10(-3).
      Nevertheless, multivariate analysis demonstrated that other autoantibodies, such
      as aCL and SSA/Ro, are more closely correlated than ANCA with some of the
      aforementioned clinical features. CONCLUSION: Our results demonstrate that ANCA
      are detectable in SLE sera and that some of them are associated with particular
      clinical manifestations. Whether ANCA plays a direct pathogenetic role in the
      vascular damage of SLE or only represents an epiphenomenon or a marker of disease
      activity remains to be elucidated.

PMID- 9779301
TI  - Increased nitric oxide in exhaled air in patients with systemic sclerosis.
AB  - OBJECTIVE: To assess the lung production of nitric oxide (NO) in patients with
      systemic sclerosis. METHODS: The NO concentration and its rate of production by
      the lungs were measured in the exhaled air in 14 patients with systemic sclerosis
      and in 12 healthy control subjects using the chemiluminescent method. RESULTS:
      The NO concentration and its rate of production were significantly increased in
      scleroderma patients (mean +/- SEM, 18.7 +/- 1.7 ppb and 5.8 +/- 0.5 nmol/min,
      respectively), as compared with control subjects (11.2 +/- 0.8 ppb and 4.3 +/-
      0.4 nmol/min, p < 0.01 and p < 0.05, respectively). CONCLUSION: The pulmonary
      production of NO is increased in scleroderma patients, which might reflect and
      contribute to the inflammatory processes of the lungs in systemic sclerosis.

PMID- 9779302
TI  - Experimentally induced stress in rheumatoid arthritis of recent onset: effects on
      peripheral blood lymphocytes.
AB  - OBJECTIVE: To examine the effects of experimentally-induced stress on the
      mobilization of peripheral blood lymphocytes (PBL) in patients with rheumatoid
      arthritis (RA) of recent onset. METHODS: Twenty-two (16 F, 6 M) patients (mean
      age 57.6 yrs.) and 23 (15 F, 8 M) healthy subjects (mean age 54.7 yrs.) were
      subjected to experimental stressors. The numbers of T-cells, B-cells, and NK
      cells were determined before and after the completion of tasks inducing physical
      and mental effort. RESULTS: The change in PBL in response to stress was about
      equal for patients and healthy subjects (p > 0.75 in all PBL subsets). In
      patients as well as in healthy subjects, the correlations between PBL and
      cortisol changes in response to stress tended to be positive, while the
      correlations between PBL and cardiovascular changes were positive in healthy
      subjects, but zero or negative in patients. Moderate to high (0.32 < or = r < or
      = 0.55) correlations between PBL changes and pain were observed. CONCLUSION:
      Experimentally-induced changes in PBL (as well as cortisol) are normal in
      patients with early RA who are receiving long term medication, but correlations
      between these changes and autonomic nervous system responses are zero or
      negative. This apparent shift in the control of the change in PBL in response to
      stress is observed in particular in patients with more pain. The
      pathophysiological significance of these findings should be clarified in
      longitudinal studies.

PMID- 9779303
TI  - Glandular and extraglandular expression of the Fas-Fas ligand and apoptosis in
      patients with Sjogren's syndrome.
AB  - OBJECTIVE: To evaluate the role of Fas-Fas ligand system-mediated apoptosis in
      the sialoadenitis and interstitial nephritis of Sjogren's syndrome. METHODS: The
      expression of Fas antigen and Fas ligand in sialoadenitis and interstitial
      nephritis was examined by immunoperoxidase staining and the reverse transcriptase
      polymerase reaction (RT-PCR) in patients with Sjogren's syndrome and in normal
      subjects. The appearance of DNA strand breaks during apoptosis was detected in
      the tissue by DNA nick end labeling methods. RESULTS: In patients with severe
      sialoadenitis, Fas antigen was strongly expressed on the ductal epithelial cells.
      In contrast, Fas antigen was not seen in the minor salivary glands of normal
      subjects nor in patients with mild sialoadenitis. In patients with massive
      mononuclear cell infiltration, some of the infiltrating cells showed the Fas
      ligand. In patients with interstitial nephritis associated with Sjogren's
      syndrome, Fas was expressed on the tubular epithelial cells, while such
      expression was not observed in control subjects without interstitial nephritis.
      In the patients with interstitial nephritis, some of the infiltrating cells
      showed the Fas ligand. Apoptotic changes were observed in the ductal epithelial
      cells, tubular epithelial cells and some infiltrating cells by DNA nick end
      labeling methods. mRNA for the Fas antigen and Fas ligand was found to be
      expressed in the labial salivary glands from all SS patients by RT-PCR.
      CONCLUSION: The findings of this study suggest that the Fas-Fas ligand system may
      play a role in the pathogenesis of the sialoadenitis and interstitial nephritis
      of Sjogren's syndrome.

PMID- 9779305
TI  - Antiquity of arthritis: spondyloarthropathy identified in the Paleocene of North
      America. off.
AB  - OBJECTIVE: Determination of the antiquity of spondyloarthropathy by examining the
      fossil record. METHODS: Fossil collections from the Paleocene and Eocene of North
      America were systematically examined to determine the occurrence and population
      frequency of spondyloarthropathy. RESULTS: Spondyloarthropathy was present in
      three mammalian orders dated at 30 to 50 million years. The frequency was 13% to
      50% in the affected genera. CONCLUSIONS: Erosive arthritis of the
      spondyloarthropathy variety is now documented to have originated at least 40
      million years ago in the Paleocene.

PMID- 9779304
TI  - Urine levels of type 1 collagen cross-linked N-telopeptides and deoxypyridinoline
      correlate with disease activity in rheumatoid arthritis.
AB  - OBJECTIVES: The aim of this study was to find out whether spot urinary
      concentrations of type 1 collagen cross-linked N-telopeptides (NTx) and
      deoxypyridinoline (Pyrilinks-D) can differentiate between active and inactive
      disease in rheumatoid arthritis (RA) and to investigate the extent to which they
      correlate with indices of disease activity. METHODS: Using enzyme-linked
      immunosorbent assays, the concentrations of NTx and Pyrilinks-D were estimated in
      spot urine samples from 25 females with active disease, 25 females with inactive
      disease, and in 25 controls. RESULTS: In Patients with active disease, urinary
      concentrations of NTx and Pyrilinks-D were significantly higher (p < 0.01) than
      in those with inactive disease or in healthy controls. In active disease there
      were significant positive correlation between urinary NTx and ESR, the swollen
      joint count, the tender joint count, and the patient's global assessment.

PMID- 9779306
TI  - Human parvovirus B19 infection is not followed by inflammatory joint disease
      during long term follow-up. A retrospective study of 54 patients.
AB  - OBJECTIVE: To investigate whether recent human parvovirus B19 (B19) infection
      provokes inflammatory arthritis, we assessed the outcome of 54 patients with
      recent B19 infection who were referred to the Department of Rheumatology.
      METHODS: Consecutive patients referred between 1985 and 1995 and found to have a
      recent B19 infection were studied retrospectively by sending a questionnaire and,
      if necessary, by physical examination. RESULTS: In the acute phase of B19
      infection, all patients had arthralgia and many also complained of myalgia and
      malaise. Arthritis was found in 61% of the patients, skin rash in 72% and fever
      in 64%. Except for the arthralgia and malaise, most of the symptoms resolved
      rapidly. After a mean followup of 5 years (SD 2.9 yrs.) none of the patients
      reported persistence of joint swelling or restricted motion. CONCLUSION: None of
      the 54 patients with recent B19 infection developed chronic arthritis.

PMID- 9779307
TI  - Blood and tissue dehydroepiandrosterone sulphate levels and their relationship to
      chronic inflammatory bowel disease.
AB  - OBJECTIVE: To evaluate the levels of dehydroepiandrosterone sulphate (DHEAS) in
      the blood and tissues of patients with inflammatory bowel disease (IBD). METHODS:
      DHEAS levels were measured by radioimmunoassay in blood from 112 patients with
      IBD: 46 with ulcerative colitis (UC) and 66 with Crohn's disease. The levels were
      compared with those in 80 healthy controls. In addition, DHEAS concentrations
      were measured in gut tissue from 40 patients (28 patients with IBD and 12 with
      other bowel disorders) who had undergone gut surgery. Correlation analyses were
      carried out between the blood and tissue levels of DHEAS. RESULTS: The mean
      levels of DHEAS in the blood were markedly lower in the two patient groups (1350
      nmol/l in UC and 1850 nmol/l in Crohn's disease vs. 3300 nmol/l in controls; p <
      0.001 and p < 0.01 respectively). A diminution below the confidence limits of the
      controls (< 2500 nmol/l) was found in 37 (79%) of the patients with UC and in 49
      (74%) of those with Crohn's disease. The remainder had DHEAS levels within the
      normal range (> 2500 nmol/l). The overall mean DHEAS concentration in gut tissue
      was 226 nmol/kg. A significant correlation was found between levels in the blood
      and those in tissues (correlation coefficient = 0.469; p < 0.002). CONCLUSION:
      These data indicate that low blood DHEAS is a feature in a majority of patients
      with UC or Crohn's disease. The possibility that there is a functional
      relationship between low DHEAS levels and some of the pathophysiologic features
      of IBD needs to be investigated.

PMID- 9779309
TI  - Minocycline-induced arthritis.
AB  - We describe seven women who developed acute polyarthritis after prolonged
      treatment with minocycline for acne. Arthritis persisted until minocycline was
      withdrawn, then recovered rapidly. A mild elevation of alanine or aspartate
      transaminase was noted in 4 patients, while pulmonary infiltrates were found in 2
      patients. Antinuclear antibodies (ANA) were persistently present throughout
      treatment in 4 patients, but were only present on one occasion in 2 women and
      were absent in one. This syndrome has been described as "drug-induced lupus"
      although, as described with other drugs, many patients do not fulfil the
      diagnostic criteria for lupus. The proposed criteria for the diagnosis of "drug
      induced lupus", which require only one clinical feature of SLE, also require a
      positive ANA test and therefore might exclude these patients. This could result
      in failure to recognise minocycline as the cause of the arthritis, and hence lead
      to prolonged illness and unnecessary investigations and treatment.

PMID- 9779308
TI  - Serum adenosine deaminase activity and its isoenzyme pattern in patients with
      systemic lupus erythematosus.
AB  - OBJECTIVE: To study the correlation between serum adenosine deaminase (ADA)
      activity and clinical activity in patients with systemic lupus erythematosus
      (SLE). The patterns of two ADA isoenzymes, ADA1 and ADA2, were also analysed in
      healthy controls and patients to determine the source of increased ADA activity
      in patients. METHODS: Total serum ADA activity (tADA) was measured
      spectrophotometrically. The isoenzyme pattern of ADA was analysed by the HPLC
      method using a specific inhibitor of ADA1, erytro-9-(2-hydroxy-3-nonyl)adenine
      (EHNA). Disease activity was assessed using the European Consensus Lupus Activity
      Measurement index (ECLAM). RESULTS: Serum tADA activity was significantly
      increased in patients compared to healthy controls (mean +/- SD; 476.9 +/- 145.3
      vs 254.0 +/- 98.9 ncat/L, p < 0.001). The isoenzyme analyses showed that the
      increased total ADA activity in the patients was mainly due to increased ADA2
      activity (371.3 +/- 154.8 vs 214.2 +/- 47.9 ncat/L in healthy controls, p <
      0.001). The mean values for ADA1 activity in the patients (64.6 +/- 37.9 ncat/L)
      and healthy controls (69.2 +/- 26.9 ncat/L) were similar. A strong correlation
      was found between serum ADA activity and disease activity as measured by ECLAM
      (Spearman's rank correlation coefficient 0.74, p < 0.0001, linear regression
      coefficient 0.68, p < 0.01). CONCLUSION: Serum ADA activity is closely associated
      with SLE activity and appears to be useful as a new disease activity parameter of
      SLE.

PMID- 9779310
TI  - Severe urinary bladder involvement in systemic sclerosis. Case report and review
      of the literature.
AB  - Lower urinary tract involvement is an uncommon manifestation of systemic
      sclerosis; however, it may represent a troublesome disturbance affecting the
      quality of life in systemic sclerosis patients. Here we report the case of a
      middle-aged woman with a 5-year history of systemic sclerosis, who developed
      severe and progressive urinary bladder sclerosis. This report is particularly
      interesting because of the severity of the bladder involvement, which required
      surgical treatment.

PMID- 9779311
TI  - Commonly used disease-modifying antirheumatic drugs in the treatment of
      inflammatory arthritis: an update on mechanisms of action.
AB  - Although disease-modifying drugs are extensively used in the treatment of
      inflammatory arthritides such as rheumatoid arthritis (RA), the actual underlying
      mechanisms of action of these agents remains somewhat unclear. Many investigators
      have studied the effects of these agents, often with particular attention being
      paid to alterations in inflammatory cytokine production, cell proliferation and
      activation, signal transduction pathways, and enzyme inhibition. By gaining a
      more complete understanding of these mechanisms, further information may be had
      regarding the pathophysiology of RA as well as other autoimmune diseases. In the
      following review we will examine some of the more recent studies of drug
      mechanisms, focusing on the most commonly used anti-rheumatic medications in the
      treatment of RA.

PMID- 9779312
TI  - Outcome of fifty-five newborns of antiphospholipid antibody-positive mothers
      treated with calcium heparin during pregnancy.
AB  - OBJECTIVE: The outcome of 55 infants born to 53 antiphospholipid antibody (aPL)
      positive mothers treated during pregnancy with calcium heparin is described.
      METHODS: The clinical state of the children was evaluated immediately after
      delivery by a clinical examination, and a neonatological check-up was performed
      no later than 24 hours after birth. Neonates with problems were transferred to
      the neonatal intensive care unit. After their discharge from hospital the
      clinical state of the babies was followed by means of interviews with the
      pediatricians and mothers for a period varying between 1.33 and 5.66 years (mean
      2.51 +/- 0.92 SD). RESULTS: The newborns comprised 30 females and 25 males,
      including 2 sets of twins, delivered between the 25th and 40th weeks of gestation
      (mean 36.69 +/- 2.91 SD). They had a mean birth weight of 2.828 g +/- 706.50 SD
      (range 800-4.000) and a mean Apgar score at 5 minutes of 9.60 +/- 0.68 SD (range
      7-10). Soon after delivery, 12 children (21.81%) were admitted to the neonatal
      intensive care unit for periods varying between 2 and 120 days (mean 30.33 +/-
      33.40 SD), after which the clinical course was normal. All of these neonates
      suffered from complications exclusively due to prematurity. Malformations and
      signs of thrombosis or other aPL-related disorders were not observed in any of
      the newborns. During the follow-up, none of the diseases suffered by the 55
      children differed from those of the normal pediatric population; in particular,
      aPL-related manifestations were never observed. CONCLUSION: These data indicate
      the absence of aPL-related problems in the offspring of aPL-positive mothers
      treated during pregnancy with calcium heparin.

PMID- 9779313
TI  - Serum soluble CD23 levels and CD23 expression on peripheral blood mononuclear
      cells in juvenile chronic arthritis.
AB  - OBJECTIVE: To assess the CD23 status in patients with juvenile chronic arthritis
      (JCA), as defined by serum soluble CD23 (sCD23) and the expression of CD23 on
      peripheral blood mononuclear cells. METHODS: Serum sCD23 levels were measured by
      ELISA in 22 patients with systemic JCA (s-JCA), in 40 patients with antinuclear
      antibody positive pauciarticular JCA (ANA+ p-JCA), and in 38 healthy controls.
      CD23 expression on T cells, B cells, and monocytes was determined by flow
      cytometry analysis of double fluorescence staining. RESULTS: Serum sCD23 levels
      were increased in both ANA+ p-JCA and s-JCA; no relation with disease activity or
      severity was found. In patients with ANA+ p-JCA, serum sCD23 levels were
      correlated with an increased percentage of B cells expressing CD23, while in
      patients with s-JCA the serum sCD23 levels were correlated with an increased
      percentage of monocytes expressing CD23. CONCLUSION: Serum sCD23 levels are
      elevated both in systemic and ANA+ pauciarticular JCA: different cell subset CD23
      expression in s-JCA and ANA+ p-JCA (i.e. monocyte or B cell, respectively)
      suggests that in pauciarticular JCA CD23 may be implicated in B cell activation
      and autoantibody production, while in systemic JCA may be involved in monocyte
      activation and in the release of inflammatory mediators.

PMID- 9779314
TI  - Lymphocytic interstitial pneumonitis preceding polyarticular juvenile rheumatoid
      arthritis.
AB  - We describe the case of a 12-year-old girl who developed lymphocytic interstitial
      pneumonitis at 2 years of age which preceded polyarticular rheumatoid factor (RF)
      positive juvenile arthritis. Her disease had a chronic active course, but showed
      a good response to combination therapy. The pathogenesis of these two immune
      processes and of the lung involvement in juvenile arthritis is discussed.

PMID- 9779315
TI  - A case of paediatric discoid lupus erythematosus evolving into SLE.

PMID- 9779316
TI  - Spinal tophaceous gout.

PMID- 9779317
TI  - Anti-PL 12 and pulmonary fibrosis in a patient ten years after silica/silicate
      dust exposure.

PMID- 9779318
TI  - Effects of glucocorticoids on bone mass in patients with polymyalgia rheumatica.
      A longitudinal study.

PMID- 9779319
TI  - Antiphospholipid syndrome and parkinsonism.

PMID- 9779320
TI  - Coexistence of primary biliary cirrhosis and isolated B27-associated peripheral
      enthesitis.

PMID- 9779321
TI  - Collagen crosslinks as markers of a therapy effect in fibromyalgia.

PMID- 9779322
TI  - Outcome assessment in patients with primary Sjogren's syndrome.

PMID- 9779324
TI  - The role of sulphasalazine in African patients with HIV-associated seronegative
      arthritis.

PMID- 9779323
TI  - Oral anticoagulation therapy of chronic skin ulcers in a patient with primary
      antiphospholipid syndrome.

PMID- 9779325
TI  - Immunogenetic study of 3 families with probands of primary hypertrophic
      osteoarthropathy.

PMID- 9779326
TI  - The ongoing evolution of behavioral couples therapy: retrospect and prospect.
AB  - Behavioral couples therapy (BCT) was first described thirty years ago, and the
      conceptual basis of the approach has been evolving ever since. Whilst BCT in its
      current form is a well established treatment for relationship problems, there are
      significant limitations to its efficacy, and there are a number of new
      developments intended to enhance the efficacy of the approach. Currently BCT
      primarily is a skills training therapy, targeting change in couple's interactions
      to promote greater relationship satisfaction. Current developments focus on
      broadening this traditional emphasis on changing couple interactions to greater
      attention to reducing negative emotional responses to partner behaviors
      (increasing acceptance), and increasing self-directed personal change efforts.
      Future developments of BCT are likely to pay greater attention to different types
      of couple interaction which are associated with sustained relationship
      satisfaction, the individual vulnerabilities partners bring to relationships, and
      the environmental stresses impinging upon the couple.

PMID- 9779328
TI  - The application of behavioral couples therapy to the assessment and treatment of
      agoraphobia: implications of empirical research.
AB  - The present review was undertaken to examine the literature regarding the role of
      the marital relationship in treatment of agoraphobia from a behavioral couples
      therapy (BCT) perspective. Both qualitative and quantitative analyses were
      conducted to evaluate (a) whether marital quality predicts treatment
      responsiveness and (b) how best to include the spouse in treatment of
      agoraphobia. Regarding the assessment of agoraphobics' relationship quality, it
      is recommended that subjectively experienced "satisfaction" with the relationship
      be distinguished from more descriptive measures of general and agoraphobia
      specific relationship "adjustment." Treatment can include the partner as a "co
      therapist" to assist with interventions directly targeted at the agoraphobia, or
      use BCT interventions to modify relationship interactions that might impede
      treatment gains. The application of BCT for these couples poses a number of
      challenges, including (a) the need to maintain a balanced treatment approach in
      an "unbalanced" system, (b) the need to target interventions at more than one
      treatment goal, and (c) the task of combining couple-focused interventions with
      those aimed at reducing phobic symptoms.

PMID- 9779327
TI  - Marital therapy in the treatment of depression: toward a third generation of
      therapy and research.
AB  - Two generations of outcome research demonstrate the potential efficacy of marital
      therapy in the treatment of depression. After reviewing treatment outcome studies
      on marital therapy for depression, we examine basic research linking aspects of
      the marital relationship to depressive symptoms. In doing so, we highlight a
      number of theoretical perspectives and research findings that can inform work
      with couples in which one spouse is depressed. Finally, we identify potential
      innovations that may lead to a third generation of marital interventions for
      depression and several avenues of inquiry for a third generation of outcome
      research on marital therapy for depression.

PMID- 9779329
TI  - Behavioral couples treatment of alcohol and drug use disorders: current status
      and innovations.
AB  - Research suggests that Behavioral Couples Therapy (BCT), tailored to treat
      alcohol problems, produces significant reduction in alcohol consumption and
      improvement in marital functioning. Having established basic clinical protocols
      for Alcohol Behavioral Couples Therapy (ABCT) and provided support for their
      efficacy, clinical researchers around the country continue to develop and study
      new applications of the basic ABCT treatment models, such as adding relapse
      prevention or Alcoholics Anonymous components. Recent research supporting the
      heterogeneity in the population of individuals with alcohol problems has prompted
      some researchers on ABCT to consider additional adaptations of the treatment
      models for specific subgroups of alcoholics, and for particular individual and
      couples characteristics. Adaptation of ABCT to treat new populations such as drug
      abusers, female alcoholics, and problem drinkers is under investigation. The
      current article provides an overview of theoretical and clinical aspects of ABCT,
      and research on efficacy of the basic model and on areas of innovation and
      adaptation to new populations. Directions for future research on ABCT are
      suggested.

PMID- 9779330
TI  - Prevention of marital dysfunction: behavioral approaches and beyond.
AB  - Marital dysfunction is a significant problem in the U.S., with far-ranging
      effects on the mental health, physical health, and economic well-being of people
      who experience it. In addition, marital discord and divorce appear to have
      adverse effects on children. This review describes the historical roots of
      current prevention programs and critically reviews marriage preparation programs
      that have been examined in the peer-reviewed literature. The results of 13
      studies suggest that behaviorally oriented, skills-based marriage preparation
      programs can lead to behavioral changes that may help prevent the emergence of
      marital dysfunction. Whereas there has been modest improvement in the methodology
      of the program evaluations, suggestions for continued improvements are made. Ways
      to enhance the effectiveness of marriage preparation programs using the
      principles of prevention are described.

PMID- 9779331
TI  - The enhancement of traditional behavioral couples therapy: consideration of
      individual factors and dyadic development.
AB  - There has been little effort by behavior therapists to develop couple
      interventions that view marriage from a content-relevant or developmental
      perspective. Consequently, we have delineated ways in which a perspective of
      intimate relationships including individual factors and dyadic development might
      guide the enhancement of traditional behavioral couples therapy (TBCT) with novel
      and improved techniques that will ultimately allows us to reach a wider range of
      distressed couples than our current interventions allows. Specifically, we
      examined the potential benefits to intervention that could occur by considering
      the impact of individual factors on relationship quality, using the literature on
      attachment patterns as an example. Further, we have discussed the potential gains
      to couple interventions that could occur by considering the impact of dyadic
      development on relationship satisfaction. We first addressed gradual changes in
      marriage, using intimacy as an example. Next we examined "stage of marriage"
      issues, using child behavior problems as an example. Finally, we considered
      whether or not a problem was chronic. Throughout, we have proposed utilizing TBCT
      as a starting point, and considering ways to enhance TBCT specifically, as it is
      the marital therapy for which we have the most information and empirical support.

PMID- 9779333
TI  - Early discharge. Risks, benefits, and who decides.
AB  - Over the last several decades, there has been a significant decrease in the
      length of hospital stays for mothers and their newborns, ranging from the average
      of 7 to 10 days before World War II to approximately 2 days in recent years. Many
      women saw the benefit of early discharge as a means to demedicalize the birth
      process, to be home with their families sooner, and to have their deliveries be a
      more positive experience. Although the trend toward shorter hospital stays was
      originally initiated by consumer interest, the recent further shortening of
      maternity stays has escalated as a result of insurance and managed care plans
      attempting to contain health care costs. With this trend toward earlier
      discharge, a litany of problems have been reported, including missed newborn
      screening, jaundice, feeding problems, missed congenital anomalies, and
      readmissions. Although cost-efficient use of health care is vital, the ultimate
      goal should not only be the prevention of unnecessary morbidity and mortality,
      but the promotion of health and well being for the child and family.

PMID- 9779332
TI  - Grandmultiparity. Is it a perinatal risk?
AB  - Increased parity is more common in lower-socioeconomic groups. Additionally, GMPs
      tend to be older. It is for these reasons that there is a tendency for an
      increased incidence of antenatal complications, such as hypertension and
      diabetes, among GMP mothers. It appears that the previous conflicting reports on
      the effect of high parity on perinatal outcome can be related to differences in
      the socioeconomic conditions of the parturient population under examination.
      Previous evidence of the unfavorable influence on perinatal outcome of high
      parity might have been biased by patient selection, because high parity is often
      inversely linked to social class. Our recent studies of the Israeli maternal
      population plus comparable reports from other countries allow us to conclude that
      GMP is not always a great cause for concern in an economically stable and healthy
      population that has access to high-quality medical care. As such, the term
      dangerous multipara should be removed from the medical literature and the focus
      of concern should shift to the organization and the delivery of quality medical
      services.

PMID- 9779334
TI  - Guidelines for management of the jaundiced term and near-term infant.
AB  - Factors believed to have contributed to the reemergence of kernicterus in the
      United States during the 1990's are discussed: these include decreased concern
      about toxicity of bilirubin in term and near-term infants, increased prevalence
      of breastfeeding, and increasingly shortened postnatal hospital stays. The
      rationale for a universal predischarge bilirubin measurement at the time of the
      routine predischarge metabolic screen is presented: the hour-specific level of
      bilirubin at discharge, plotted on an Hour-Specific Bilirubin Nomogram, improves
      prediction of risk of excessive jaundice postdischarge and facilitates safe, cost
      effective follow-up. This minimizes repeat bilirubin measurements and maximizes
      recognition of confounding variables and risk of hyperbilirubinemia so that
      timely, minimally invasive, preventive therapy can be instituted if needed.

PMID- 9779335
TI  - Severe neonatal hyperbilirubinemia. A potential complication of glucose-6
      phosphate dehydrogenase deficiency.
AB  - G-6-PD deficiency is frequently associated with neonatal hyperbilirubinemia,
      which may be severe enough to cause kernicterus and death. Because of its
      association with acute trigger-induced hemolytic crises, G-6-PD deficiency
      associated neonatal hyperbilirubinemia has been labelled as hemolytic in origin.
      In this article, the authors summarize recent evidence demonstrating that
      hemolysis cannot in and of itself be responsible for jaundice and that decreased
      bilirubin elimination plays a major role in its pathogenesis.

PMID- 9779336
TI  - Neonatal risk scoring systems. Can they predict mortality and morbidity?
AB  - Physiology-based illness severity scores are proving their value through a wide
      variety of practical applications. The theoretical disadvantages noted in Table 1
      have not turned out to be major problems, whereas the advantages have been quite
      real. Numerous studies have reported insightful comparisons between treatment
      groups, between NICUs, between countries, between eras, and over the course of
      care. Many institutions have implemented routine collection of physiology-based
      newborn scores. The answer to the question posed in the title is yes; neonatal
      risk scoring systems can predict some mortality and some morbidity. However, it
      is clear that this function is much less important than their application as a
      means of improving quality and cost. Future development will depend on
      commercially viable applications.

PMID- 9779337
TI  - Intervention programs for premature infants. How and do they affect development?
AB  - Over the past 30 years, a variety of intervention programs for the enhancement of
      the neurodevelopmental status of premature infants have been implemented with
      confusing outcomes. In addition, diametrically different forms of therapy that
      rest on contrasting theories have led, paradoxically, to similar results. This
      article systematically examines and analyses the various modes of therapy and
      their underlying theoretical mechanisms. Skin-to-skin contact (kangaroo care) is
      suggested as the intervention that most logically meshes the premature infant's
      need to develop state regulation while facilitating sequential sensory
      development and promoting mother-infant attachment.

PMID- 9779338
TI  - Does transient hypothyroxinemia cause abnormal neurodevelopment in premature
      infants?
AB  - THOP is a relatively common condition whose long-term effects remain uncertain.
      The preponderance of evidence indicates that at the very least THOP is a marker
      of elevated risk of neurodevelopmental adversity, but whether this association is
      truly causal and whether thyroxine treatment in the neonatal period can prevent
      adverse outcome is as yet unknown. Since the number of infants born and surviving
      at very early gestations continues to increase, the importance of this condition
      will be magnified in the future. The major difficulty in establishing the causal
      role of THOP is the tangled time order of events in the early neonatal period. It
      is therefore unlikely that further observational studies will advance
      understanding. Energies should be focused on Assessing neurodevelopment
      objectively in survivors in each of the TRH trials. Developing a new multicenter
      trial of newborn supplementation with thyroid hormone that is carefully planned
      to have sufficient power to assess neurodevelopment in treated and untreated
      infants under a variety of baseline conditions.

PMID- 9779339
TI  - The role of human milk fortification for premature infants.
AB  - This article focuses on the current experience with the use of fortified milk in
      feeding premature infants. The use of fortified human milk provides the premature
      infant adequate growth, nutrient retention, and biochemical indices of
      nutritional status when fed at approximately 180 mL/kg/d compared with
      unfortified human milk. When compared with preterm formula, the feeding of
      fortified human milk may provide significant protection from infection and
      necrotizing enterocolitis. Neonatal centers should encourage the feeding of
      fortified milk for premature infants. Skin-to-skin contact is a reasonable method
      to enhance milk production while potentially facilitating the development of an
      enteromammary response.

PMID- 9779340
TI  - The role of antibiotic therapy in the prevention of prematurity.
AB  - Prematurity is the leading cause of perinatal morbidity and mortality in the
      industrial world, occurring in 4% to 9% of all deliveries, a rate that has
      remained unchanged during the past decades. Despite the relative minority of
      obstetric patients affected by this problem, prematurity is responsible for
      approximately 70% to 80% of perinatal morbidity and mortality corrected for
      congenital anomalies. To date, treatment modalities (tocolysis) that have been
      applied to patients who have preterm labor (PTL) and preterm premature rupture of
      membranes have been found to be of limited value in reducing both the rate of
      prematurity and of perinatal mortality and morbidity. A possible explanation for
      this failure in prevention of prematurity can be attributed to the poor
      understanding of the mechanisms of parturition in general and the pathophysiology
      of PTL in particular.

PMID- 9779341
TI  - Prevention of neonatal group B streptococcal infections. Is there a rational
      prevention strategy?
AB  - Clinicians, both obstetric and pediatric, are currently faced with the need to
      choose treatment strategies to reduce the persistent high incidence of early
      onset GBS neonatal disease without being equipped with adequate data to choose
      conclusively which of the proposed strategies is ideal. There is an urgent need
      for well-designed prospective randomized trials comparing the various prevention
      protocols so as to resolve conclusively the controversy. The ultimate prevention
      strategy may well be a successful maternal immunization program.

PMID- 9779342
TI  - Rationale and potential use of cytokines in the prevention and treatment of
      neonatal sepsis.
AB  - Despite advances in the use of newer antimicrobials and aggressive supportive
      care, sepsis and its sequalae remain a major source of morbidity and mortality in
      the neonate. The VLBW neonate is especially at high risk. We and others have
      demonstrated that neonatal MNC are deficient in their production of G-CSF and GM
      CSF, which, in part, may explain the neonates propensity to develop neutropenia
      during times of sepsis. G-CSF and GM-CSF have been shown to both enhance neonatal
      neutrophil superoxide production in vitro and to increase circulating neutrophil
      numbers through expansion of the NSP in the BM in neonatal rats and humans. G-CSF
      is protective (if given with or before antibiotics) during experimental GBS in
      the neonatal rat and appears to be well tolerated (both short term and 2 years
      after its use) in the human neonate. In a phase II randomized pilot multicenter
      study, GM-CSF prophylaxis in the VLBW neonate was well tolerated during 4 weeks
      of administration and was noted to have significantly reduced the incidence of
      nosocomial infections. Future efficacy and safety studies in more neonates need
      to be completed and assessed before the routine pharmacologic use of G-CSF or GM
      CSF is recommended to prevent and treat neonatal sepsis.

PMID- 9779343
TI  - Liquid ventilation.
AB  - For decades, the fluid-filled lung has been a valuable research model for
      understanding normal and abnormal pulmonary physiology. It has lagged behind,
      however, as a useful therapeutic tool. Recently, the potential applications of
      perflubron's physicochemical and biologic properties have been realized. In
      animal models of several types of hypoxic respiratory failure, perflubron's
      efficacy in improving gas exchange and compliance has been demonstrated.
      Preliminary clinical studies of PLV in neonates who have RDS and CDH, and in
      children and adults who have ARDS have shown promise. Pivotal prospective,
      controlled studies have yet to be completed.

PMID- 9779344
TI  - Role of corticosteroids in neonatal blood pressure homeostasis.
AB  - Corticosteroids are commonly administered during the perinatal period because of
      their diverse actions on various organ systems, both at the cellular and
      molecular level, and because of their effect on maturational physiology. In
      particular, in situations of refractory cardiovascular collapse, corticosteroids
      are used by many clinicians as a last-chance therapeutic modality. This article
      reviews the mechanism of neonatal blood pressure homeostasis with particular
      emphasis on the postnatal adaptation of the neonate's cardiovascular system and
      adrenal function to extrauterine life. Evidence also is provided about the
      existence of a hypocortisolism state in the sick or stressed very low birth
      weight infant.

PMID- 9779345
TI  - Resuscitation with room-air or oxygen supplementation.
AB  - An accumulating body of data indicates that optimal newborn resuscitation is not
      performed with 100% oxygen. On the contrary, ambient air seems to have several
      advantages compared with supplemental oxygen. Present guidelines on newborn
      resuscitation should be critically reviewed and revised according to scientific
      evidence.

PMID- 9779346
TI  - Ischemia and reperfusion injury. The ultimate pathophysiologic paradox.
AB  - It seems clear that the abundance of potential treatment options reflects the
      dearth of proved, effective options. Thus, although we appear to be on the brink
      of many potentially major breakthroughs in treatment, there currently remains a
      multitude of unanswered questions and the need for further study. At this point
      clinical recommendations must be limited to supportive care with moderation:
      oxygenation without hyperoxia; ventilation without hypocarbia; avoiding extremes
      of blood pressure, hematocrit, blood glucose, and body temperature.
      Unfortunately, data from human trials are extremely limited and often poorly
      controlled. Furthermore, even those few existing human studies have rarely--if
      ever--dealt with newborns infants (Table 2). In addition, many of the existing
      studies do not relate to generalized asphyxia but rather to single-organ
      reperfusion insults. Finally, there is the critical issue of timing.
      Unfortunately, much of the existing experimental data relate to prophylaxis
      rather than treatment, severely limiting their potential for clinical
      applicability. Interventions may have quite different effects when administered
      at different phases of this most intricate process. Hyperglycemia, for example,
      may be neuroprotective before an insult but detrimental if induced after an
      asphyxial episode. Conversely, the NMDA blocker MK-801 can adversely affect
      outcome when given before a global asphyxial insult but can reduce seizure
      related damage when given during the hyperexcitability phase. Insulin-like growth
      factor is also neuroprotective only when given after an insult, but it is not
      helpful if given before. An intimate understanding of the pathophysiologic
      processes involved is essential before any attempts at applying the diverse data
      derived from numerous animal studies to the human situation in an intelligent
      manner. Future studies may focus on cocktails of different mixtures of the
      compounds discussed or on single multipotential drugs, which would make possible
      a multipronged approach. However, it is essential to investigate fully the
      potential for toxic drug interactions, as some combinations may be produce
      serious consequences. For example, Gluckman and Williams evaluated the potential
      of combining calcium channel blockers with NMDA receptor antagonists in hypoxic
      ischemic rats and found that this combination led to rapid cardiovascular
      collapse. Other enticing approaches for future investigations will probably
      include some genetic-engineering-related studies in attempt to enhance endogenous
      antioxidant defenses with regulon stimulation or the administration of
      neurotrophic growth factors. Unavoidably, the trip from the laboratory to the
      bedside must of necessity be an arduous and rigorous one.

PMID- 9779347
TI  - Decision-making and the role of surrogacy in withdrawal or withholding of therapy
      in neonates.
AB  - Ideally, decisions to forego life-sustaining treatments in neonates should be
      arrived at by a team of expert physicians, nurses, and social workers, together
      with both parents. Surrogates, however, may occasionally have other
      considerations than the best interest of the ill neonate, and sometimes the
      postpartum mother may be temporarily incompetent to make such grave decisions.
      Therefore, a careful assessment of the parents' decision is required. Physical
      help in the caring for the child, psychologic family counseling, educational and
      vocational assistance, and even quality institutionalization must be provided if
      the parents are unable to fully care for the child.

PMID- 9779348
TI  - Recent approaches to the management and prevention of respiratory syncytial virus
      infection.

PMID- 9779349
TI  - Current and future therapy of invasive fungal infections.
AB  - Major increases in the incidence of systemic fungal infections have been observed
      during the past three decades, particularly in immunocompromised patients. A
      critical need exists for new antifungal agents to treat these life-threatening
      invasive fungal infections. The review of the development of antifungal therapy
      provided in this chapter indicates the increased interest in this very special
      area of infectious diseases. Even though newer and less toxic antifungal agents
      are currently available for clinical use, innovative research in antifungal drug
      discovery may eventually produce more promising antifungal agents.

PMID- 9779350
TI  - New approaches to the diagnosis, treatment, and prevention of chlamydial
      infection.

PMID- 9779351
TI  - Fungal sinusitis.
AB  - Noninvasive fungal sinusitis usually occurs in individuals with a poorly draining
      maxillary sinus. The infection can be cured by surgical removal of the hyphal
      mass. In contrast, allergic fungal sinusitis is an upper respiratory disease with
      an immunopathology similar to that of allergic bronchopulmonary aspergillosis.
      Surgical debridement and therapy with topical or systemic steroids are
      recommended. Acute and chronic invasive fungal sinusitis are extremely serious
      infections requiring aggressive therapy, including extensive surgical debridement
      and appropriate antifungal chemotherapy. For acute invasive fungal sinusitis in
      the neutropenic host, survival depends chiefly on bone marrow recovery.

PMID- 9779352
TI  - Infections in the elderly--new developments.

PMID- 9779353
TI  - Diagnosis of invasive fungal infections: advances in nonculture systems.

PMID- 9779355
TI  - Infectious agents and the etiology of chronic idiopathic diseases.
AB  - At the end of the nineteenth century, the field of microbiology was born, and the
      infectious nature of many previously unexplained diseases was illuminated as
      powerful new technology was applied. At the end of the twentieth century, the
      etiology of myriad chronic diseases remains unexplained. We have argued that many
      of these diseases have clinical, epidemiological, and pathological features that
      suggest a role for microbes in their pathogenesis. Although definitive evidence
      of microbial disease causation is lacking, we believe that new technologies, such
      as sequence-based microbial identification, will successfully be applied to many
      of these chronic idiopathic diseases in the near future. As novel pathogens and
      previously described pathogens are revealed as the causative agents for some of
      these conditions, new diagnostic, preventive, and therapeutic modalities may
      emerge, transforming some diseases from idiopathic and chronic, to infectious and
      curable.

PMID- 9779354
TI  - Antiretroviral chemotherapy.

PMID- 9779356
TI  - Babesiosis.

PMID- 9779357
TI  - Advances in the prevention and management of traveler's diarrhea.

PMID- 9779358
TI  - Human herpesvirus 8 and its role in the genesis of Kaposi's sarcoma.

PMID- 9779359
TI  - Lung abscess: pathogenesis, diagnosis and treatment.

PMID- 9779360
TI  - Hepatitis G virus and related flaviviruses: pathogens or passengers?

PMID- 9779361
TI  - New perspectives in adenoviruses.

PMID- 9779362
TI  - An approach to the historical evolution of surgical operations for the treatment
      of gastroesophageal reflux.
AB  - There exists great confusion concerning the different techniques for the
      treatment of gastroesophageal reflux. For instance, we apply the term
      fundoplication to different operations that often have nothing to do with the
      original description, and there is a serious lack of knowledge of the historical
      origins of many of these operations. This analysis is the result of a large
      review of the operations, and of the original papers as they were published.

PMID- 9779363
TI  - Gastroesophageal reflux triggers proliferative activity of the submucosal glands
      in the canine esophagus.
AB  - The effect of experimental gastroesophageal reflux on mitotic activity in the
      squamous epithelium, as well as in the submucosal glands, of the esophagus was
      investigated in dogs. The lower esophageal sphincter was destroyed in four dogs
      using a Wendel cardioplasty, a simple esophagotomy was carried out in four other
      animals, and four unoperated dogs were taken as controls. Two weeks later,
      mucosal samples from the esophagus were taken after in vivo labeling of the
      animals with bromodeoxyuridine. In all mucosal samples the proliferative
      parameters were estimated in the squamous epithelium, in the submucosal glands
      and in their excretory ducts. After the cardioplasty, the proliferative
      parameters were increased (P < 0.05) not only in the esophageal epithelium but
      also in the submucosal glands and in their excretory ducts (P < 0.05). The
      amplitude of the proliferative response was more than ten times larger in the
      latter than that in the surface epithelium. Gastroesophageal reflux is a potent
      proliferative stimulant to the esophageal squamous epithelium, but also to the
      cells of the submucosal esophageal glands and their excretory ducts.

PMID- 9779365
TI  - 'Carditis': an objective histological marker for pathologic gastroesophageal
      reflux disease.
AB  - In a prospective endoscopic and bioptic study, 141 control subjects and 359
      patients with symptoms of gastroesophageal reflux (GER) were included to
      determine the prevalence of cardial epithelium inflammation or 'carditis' and to
      determine the prevalence of Helicobacter pylori in this area. Two biopsies at the
      antrum, four distal to the squamous-columnar junction and two proximal in the
      esophageal mucosa, were taken. Patients with gastroesophageal reflux were divided
      into four groups, according to the severity of endoscopic findings: patients
      without esophagitis, patients with erosive esophagitis, patients with short
      segment and long-segment Barrett's esophagus (BE). Control subjects had normal
      histological findings at the cardia in 90% of cases, fundic mucosa being present
      twice as cardial epithelium. Carditis was present in 8% of cases and intestinal
      metaplasia (IM) in 2%. On the contrary, patients with GER had carditis in nearly
      50% of cases. Intestinal metaplasia was present in 12% of cases with GER without
      esophagitis or erosive esophagitis, in 35% of cases with short-segment BE and in
      65% of the cases with long-segment BE. IM at the antrum was present in only 5% of
      cases. Helicobacter pylori at the squamous-columnar junction was present in 13%
      of control subjects and in 30% of the patients with GER. It is concluded that
      carditis is an easy and objective marker for the presence of chronic
      gastroesophageal reflux and the presence of Helicobacter pylori at this region
      must be carefully evaluated in order to determine some pathogenic role for the
      development of Barrett's esophagus.

PMID- 9779364
TI  - Luminal hypertonicity and the susceptibility of rabbit esophagus to acid injury.
AB  - The esophagus is regularly exposed to hypertonic luminal environments, some of
      which have the capacity to increase epithelial permeability. The present
      experiments were designed to determine what impact such environments have on
      epithelial resistance to injury by acid. Rabbit esophageal epithelium mounted in
      Ussing chambers was exposed to luminal acid while monitoring electrical
      resistance (R), a marker of epithelial permeability, and morphology was assessed
      in tissues luminally pretreated with either urea (1 M), mannitol (1 M), or normal
      Ringer. Hypertonic mannitol, which had little effect on R, was associated with a
      minor increase in susceptibility to acid injury, pH 1.6. In contrast, hypertonic
      urea lowered R and was associated with marked injury upon exposure to acid. This
      susceptibility to acid injury occurred within 15 minutes of exposure and
      converted a non-damaging concentration of acid (pH 2.0) to a damaging one.
      Moreover, urea's effects were abolished if it was removed from the bath allowing
      R to return to baseline before acidification. We conclude that hypertonic luminal
      environments that impair epithelial barrier function predispose the esophagus to
      acid injury. Such findings may provide insight into additional mechanisms
      contributing to the development of heartburn following meals.

PMID- 9779366
TI  - Influence of age and gender on gastroesophageal reflux in symptomatic patients.
AB  - Studies have reported that normal males have significantly more physiologic
      gastroesophageal reflux (GER) than women but little difference in reflux
      parameters is seen between younger and older normal individuals. The aims of this
      study were to investigate the influence of age and gender on GER in symptomatic
      patients. We reviewed 353 24-h pH studies performed in patients with reflux
      symptoms. The following parameters were assessed: % time pH < 4 of total, upright
      and supine periods; total reflux episodes; total reflux episodes > 5 min; longest
      reflux episode. These parameters were analyzed according to age and gender using
      non-parametric tests. The median age was 47 years and this was used as the cutoff
      between younger and older patients. Also, an elderly group (age > or = 65) was
      analyzed. Age did not influence % time pH < 4 for total, upright and supine
      periods. However, older symptomatic patients had longer reflux episodes. As with
      normal subjects, male patients had significantly (P < 0.05) more reflux than
      females, comparing median values for the percentage times pH < 4: total 4.7 vs
      2.7%; upright 5.2 vs 3.3%; supine 1.2 vs 0.4%; total reflux episodes 63 vs 45;
      episodes > 5 min (2 vs 0) and longest reflux episode 9 vs 5 min. Therefore,
      different cutoff values may be necessary for males and females in diagnosing
      abnormal reflux.

PMID- 9779367
TI  - A patient's perspective on the management of peptic esophageal stricture:
      experience and results in 113 consecutive cases.
AB  - A retrospective analysis of 113 consecutive cases of benign esophageal stricture,
      all secondary to gastroesophageal reflux, 100 treated conservatively, 13 treated
      surgically, has been carried out in conjunction with a postal questionnaire of
      patients. Patients were requested to grade both their swallowing ability and the
      acceptability of their treatment. Of those responding to questionnaire, 88% of
      patients treated conservatively found their treatment acceptable or better, and
      72% were left with either no or minimal restriction of diet. There was no
      correlation between either the total number or frequency of dilatations and the
      result achieved. Similarly, patient satisfaction appears largely independent of
      these variables. Doctors should be wary of taking recurrence of a stricture after
      initial dilatation as indicating a poor eventual outcome or a dissatisfied
      patient. There was no difference in terms of either the result or patient
      satisfaction between conservatively treated and surgically treated patients.

PMID- 9779368
TI  - The natural restricturing process after dilatation of peptic esophageal
      strictures.
AB  - The study analyzes the natural esophageal restricturing process after dilatation
      of peptic esophageal strictures. Fifty patients (male/female: 30/20) with median
      age 71 years (range 20-87) with peptic esophageal strictures were dilated with
      hydrostatic balloons to 20 mm and followed up for 12 months. Stricture size was
      measured with a 'balloon pull-through' technique before the dilatations, and at
      follow-ups after 6 and 12 months. The restricturing rate was defined as the
      difference in stricture diameter at two measurements divided by the time
      interval. The mean restricturing rate during the first and last 6 month periods
      were 0.99 and 0.02 mm/month respectively (P < 0.001), and during the first 6
      months the restricturing rates were 1.98 and 0.69 mm/month in patients redilated
      and not redilated respectively (P < 0.001). A tight stricture at the initial
      dilatation, a long history of reflux symptoms and a short history of dysphagia
      were all significantly related to a high restricturing during the first 6 months
      (P < 0.001).

PMID- 9779369
TI  - Lower esophageal sphincter measurement in four different quadrants in normals and
      patients with achalasia.
AB  - In order to determine the endoluminal pressure force distribution, the pressure
      in the lower esophageal sphincter (LES) and esophageal body was recorded in
      healthy volunteers and patients with achalasia, using a new waterperfused
      circular four-channel-sleeve (FCS) manometry catheter. The median lower
      esophageal sphincter pressure (LESP) and interquartile range in healthy control
      subjects (group 1) was significantly higher in the left lateral quadrant: 37 (28
      43) mmHg (channel III) (P < 0.001), in comparison to the right lateral: 24 (20
      25) mmHg (channel I), anterior: 22 (18-30) mmHg (channel II), and posterior
      quadrant: 24 (22-28) mmHg (channel IV). The median LESP in achalasic patients
      (group 2) was significantly increased in channel I: 31 (27-36) mmHg, channel II:
      35 (28-39) mmHg, and in channel IV: 29 (26-237) mmHg (P < 0.001) when compared to
      controls. The detected pressure of the left lateral quadrant of the LES was not
      found to be significantly different from controls: 38 (29-39) mmHg. The median
      contraction amplitude of healthy subjects was significantly higher when compared
      with achalasic patients (P < 0.001). In patients with achalasia (group 2) the
      median contraction amplitude of the proximal esophagus was significantly higher
      than the distal contraction amplitude. In contrast, healthy volunteers showed a
      reverse relationship. No asymmetric pressure force was detected with the FCS in
      the proximal or distal esophageal body in either group. In conclusion, the
      abolition of the normal manometric LES asymmetry in patients with achalasia might
      indicate regional variations of muscle functions in the high pressure zone of the
      gastroesophageal junction (GEJ).

PMID- 9779370
TI  - Respiratory management and outcome of non-malignant tracheo-bronchial fistula
      following esophagectomy.
AB  - Tracheo-bronchial lesions with air leak are rare but a catastrophic complications
      of esophageal resections. We analyzed the management and outcome of 31 patients
      who developed a non-malignant lesion of the trachea or main stem bronchus after
      esophagectomy for esophageal cancer. All patients initially required endotracheal
      intubation to control respiratory distress. A modified respiratory therapy with a
      reduced tidal volume and high respiratory rate markedly decreased the air leakage
      from 2.8 to 1.1/min (P < 0.001). Early extubation was possible in 23 patients
      with a complete healing or decrease of the fistula size. Jet ventilation,
      endoluminal stenting of the fistula, bronchoscopic fibrin sealing of the fistula,
      and surgical closure of the fistula with a muscular pedicle flap were attempted
      with variable success in patients with otherwise not manageable air leaks. Ten of
      the 31 patients (33%) died during the postoperative course, in eight out of 10
      patients, postoperative mortality resulted from an unhealed lesions at the
      bifurcation or in the left main stem bronchus. These data show that reduction of
      airway pressure and spontaneous breathing are the key to closure of the airway
      leak. The entire armamentarium of respiratory, bronchoscopic, and surgical
      techniques must be available for a successful management of these patients.

PMID- 9779371
TI  - Bronchogenic cyst of the esophagus with high tumor marker levels--a case report
      and review of the literature.
AB  - Bronchogenic cysts of the esophagus are rare in comparison with the relatively
      common bronchogenic cyst of the lung. Only a few cases have been reported in
      literature since 1930. We report on a case of a 43-old-male with a bronchogenic
      cyst in the distal esophagus, which was misdiagnosed as a malignant esophageal
      tumor based on preoperative imaging and high levels of the tumor markers CA 19-9
      and CA 125.

PMID- 9779373
TI  - What's new in pathology, pathophysiology and management of benign esophageal
      disorders?

PMID- 9779372
TI  - Massive hemorrhage after biopsy of an esophageal polyp.
AB  - Esophageal vascular malformations are very rare. Herein, we describe a rare polyp
      formed by an abnormally large vessel that bled profusely after biopsy. Despite
      endoscopic procedures, the patient continued to bleed and underwent emergency
      surgery. Histopathological examination revealed an abnormally large blood vessel
      with a thick wall in the upper part of the lamina propria mucosae and covered by
      squamous cell epithelium. The elevated lesion, which was endoscopically diagnosed
      a small polyp, was in fact an abnormally large artery covered by squamous cell
      epithelium. Massive bleeding after biopsy of an esophageal polyp is apparently so
      rare that it has not, as yet, been described.

PMID- 9779374
TI  - Differential effects in vivo of thyroid hormone on the expression of surfactant
      phospholipid, surfactant protein mRNA and antioxidant enzyme mRNA in fetal rat
      lung.
AB  - Antenatal administration of triiodo-L-thyronine (T3) to late gestation rats
      resulted in decreased lung antioxidant enzyme (AOE) activity but increased
      surfactant phospholipids. In fetal rat lung explant cultures, T3 decreased the
      expression of surfactant proteins (SP) A and B. There have been no reported
      studies of the simultaneous in vivo developmental influence of T3 on both
      pulmonary AOE and SP gene expression. We hypothesized that antenatal T3 treatment
      would cause differential regulation of surfactant phospholipid, SP, and AOE genes
      in the late gestation fetal rat. Timed pregnant rats received intramuscular
      injections of either T3 (7 mg/kg) or placebo on days 19 and 20 of gestation and
      fetuses were delivered on day 21. Fetal lung SP-A, SP-B, SP-C, and AOE mRNA
      levels were studied by Northern analysis. AOE mRNA levels were further
      quantitated by solution hybridization. Total lung phospholipids (TPL) and
      disaturated phosphatidylcholine (DSPC) content were quantitated by a phosphorus
      assay. T3 significantly increased TPL and DSPC content, and significantly
      decreased the expression of SP-A, SP-C, CuZnSOD, and catalase genes. Because of a
      crucial interplay of these factors for normal lung function at the time of birth,
      the molecular mechanisms by which these apparently opposing changes are
      accomplished warrant further investigation.

PMID- 9779375
TI  - Taurine protects rat bronchioles from acute ozone exposure: a freeze fracture and
      electron microscopic study.
AB  - Dietary taurine has been shown to protect rat and hamster lung epithelia from
      acute oxidant injury. One of the earliest morphologic criteria of oxidant injury
      is the alteration of tight junctions of the peripheral lung airways. In the
      present study, we have used this criteria to evaluate whether taurine was capable
      of protecting rat lungs from ozone exposure. Rats were treated for 10 days with
      50% taurine in their drinking water, prior to exposure to 2 ppm of ozone for 3
      hours. The lungs from rats pretreated with taurine and exposed to ozone were
      compared to untreated rats exposed to ozone and air-exposed controls. At 2, 6,
      12, 24, 48, and 72 hours after exposure to air or ozone, rats were anesthetized
      and the lungs perfusion-fixed through the right side of the heart with a solution
      of glutaraldehyde and paraformaldehyde. Light microscopy revealed the typical,
      mild inflammatory cell infiltrate beginning at 6 hours after ozone exposure in
      bronchioles, alveolar ducts, and surrounding alveoli which was absent in the
      lungs of animals treated with taurine. Electron microscopic analysis of thin
      sections indicated alterations in tight junctions which was confirmed by tracer
      studies using ruthenium red and lanthanum. Alterations in airway epithelium tight
      junctions were seen 2 and 6 hours after ozone treatment and only in the 2-hour
      tissues from animals pretreated with taurine prior to ozone exposure. Freeze
      fracture replicas from all exposure groups by electron microscopy revealed that
      only the 2- and 6-hour groups showed alterations in tight junctions. The
      alterations were characterized by decreased number of fibrils and breaks in the
      fibrils. Rats treated with taurine and exposed to ozone exhibited these
      alterations focally at 2 hours exposure and no changes were noted at 6 hours post
      ozone exposure. These data confirmed previous findings that injury induced by
      ozone is transient and that taurine protects the bronchioles from this form of
      oxidant injury.

PMID- 9779376
TI  - Binding of guanine nucleotides to bronchial membranes: effect of maturation.
AB  - Guanosine 5-[y-thio]triphosphate ([35S]GTP gamma S) binding to guinea pig
      bronchial membranes from immature and mature guinea pigs was rapid (Kon: 3.8 x
      10(5) mol-1 min-1), saturable (Bmax: 160 pmoles/mg protein) and of high affinity
      (Kd: 0.6 microM). [35S]GTP gamma S rapidly dissociated in the absence of
      magnesium (Koff: 0.06 min-1), but 50 mM magnesium inhibited the dissociation.
      Maturation did not alter the affinity of the ligand, but Bmax (pmoles/mg DNA) was
      greater in preparations from mature animals (929 +/- 16 vs. 620 +/- 64). [35S]GTP
      gamma S was displaced by guanine nucleotides with a rank order of potency of GDP
      beta S = Gpp(NH)p > GDP > GTP, but not by ATP. We conclude that [35S]GTP gamma S
      is a specific and useful method to quantitate bronchial membrane-bound GTP
      binding proteins. The technique shows that there is a significant increase in the
      cellular content of G-proteins during maturation.

PMID- 9779377
TI  - Chemokine mRNA alterations in newborn and adult mouse lung during acute
      hyperoxia.
AB  - Chemokines play a major role in the recruitment of inflammatory cells during
      acute lung injury. Adult and newborn C57BL/6 mice were exposed to > 95% oxygen
      for up to 72 hours and 7 days, respectively. Chemokine mRNA abundance was
      evaluated in whole lung RNA by ribonuclease protection assay and in tissue
      sections by in situ hybridization. Monocyte chemoattractant protein (MCP)-1,
      macrophage inflammatory protein (MIP)-2, and interferon gamma-induced protein
      (IP)-10 mRNAs were present in whole newborn lung by 4 days of hyperoxia and were
      markedly elevated by 7 days. Levels of mRNA for MCP-1, MIP-1 alpha, and MIP-2
      were elevated to a lesser extent by 72 hours of hyperoxia in adults. MCP-1 mRNA
      abundance was moderately elevated in scattered areas of perivascular tissue,
      peribronchiolar tissue, and the alveolar interstitium in 4-day hyperoxic newborns
      and markedly upregulated diffusely throughout the peripheral airspaces in 7-day
      hyperoxic newborns. MCP-1 mRNA abundance was limited to scattered perivascular
      areas and airspaces in 72-hour hyperoxic adults. These differences in the
      intensity, timing, and distribution of chemokine mRNA abundance between adult and
      newborn mice may help to explain the marked differences in their susceptibility
      to oxygen injury.

PMID- 9779378
TI  - Innate immunity, cytokines, and pulmonary host defense.
AB  - Effective host defense against bacterial infection is dependent on the activation
      and recruitment of phagocytic cells. The initiation, maintenance, and resolution
      of this inflammatory response in the setting of bacterial pneumonia is dependent
      on the expression of cytokines. As the complexities of the host-pathogen
      interaction are further dissected and unraveled, immunologic manipulation of
      cytokine expression will likely become an important adjuvant therapy in the
      treatment of serious lung infections.

PMID- 9779379
TI  - The role of atypical pathogens: Mycoplasma pneumoniae, Chlamydia pneumoniae, and
      Legionella pneumophila in respiratory infection.
AB  - Infections caused by M. pneumoniae, C. pneumoniae, and Legionella spp. are
      important causes of community-acquired pneumonia (CAP). In the past decade,
      considerable new information has come to light concerning these organisms.
      Despite this, debate continues concerning the syndromic approach to CAP and the
      scientific merit of lumping these pathogens together. Because the etiologic
      diagnosis of these pathogens is established only in a minority of cases, the true
      prevalence tends to be underestimated. In clinical practice, these pathogens are
      often empirically treated. More rapid and cost-effective diagnostic techniques
      are needed so that the clinical course of patients with these infections can be
      better characterized.

PMID- 9779380
TI  - Mycobacteria as pathogens of respiratory infection.
AB  - As the result of a formidable effort, the recent TB epidemic in the United States
      has abated; however, major questions remain as the risk of TB diminishes. Will we
      maintain an adequate public health effort not only to prevent another resurgence
      of TB but also to renew our pursuit of TB elimination? Do we have the will to
      extend the fight against TB worldwide as the TB threat in the United States
      declines? What is the best way to incorporate new diagnostic technology into
      routine practice? What are the best strategies for preventing and treating TB in
      AIDS patients? From the standpoint of NTM lung diseases, the major challenges are
      to educate clinicians about the variety and clinical presentation of NTM lung
      pathogens in order to recognize NTM lung disease as early as possible and to
      maximize treatment options. Hopefully, we can also improve upon the recent
      unprecedented progress in treatment regimens for NTM diseases of all types.

PMID- 9779381
TI  - Resistance issues and treatment implications: pneumococcus, Staphylococcus
      aureus, and gram-negative rods.
AB  - During the last decade there has been an unexpectedly rapid evolution of
      antimicrobial resistance in the respiratory pathogens for community- and hospital
      acquired pneumonia. In order to choose the most optimal therapy for their
      patients, it is essential that physicians be aware of the prevalence and
      mechanisms of resistance and their implications on the effectiveness of the
      various antimicrobials.

PMID- 9779382
TI  - Intrapulmonary concentrations of antimicrobial agents.
AB  - The delivery of antimicrobial agents to the site of infection has always been
      considered important. Lung infections are typically localized to the bronchial
      mucosa, endothelial lining fluid, and/or alveolar macrophages. Significant
      advances have been made in measuring antimicrobial concentrations at these sites,
      although some of the methods need further refinement and standardization.
      Relating various intrapulmonary site concentrations to efficacy or treatment
      failure requires further study. This article reviews the theory and methods
      relating to the measurement of intrapulmonary delivery of antimicrobial agents,
      and compares the intrapulmonary delivery of agents commonly used for the
      treatment of lower respiratory infections.

PMID- 9779383
TI  - Advances in the macrolides and quinolones.
AB  - The widespread, frequent clinical use of the macrolides and quinolones has led to
      resistance in several species. With the prevailing increase of resistance, new
      developmental compounds with improved spectra, pharmacokinetics, and reduced
      adverse effects are required, coupled with logical use of the current
      armamentarium.

PMID- 9779384
TI  - Airway infection.
AB  - Bronchitis in its acute and chronic forms with recurrent acute exacerbations is
      one of the most common reasons for physician visits, accounting for a significant
      cost to the health-care system, lost work days, and increased morbidity and
      mortality. Smoking and recurrent lower respiratory tract infections are major
      risk factors for chronic bronchitis. Therefore, smoking cessation and vaccination
      strategies are cornerstones of management in terms of halting disease progression
      and reducing the frequency of infectious exacerbations. Bacterial infection is
      the main culprit in acute flares of the disease. Routine antimicrobial therapy
      fails in a significant number of patients, and therapeutic failures lead to
      increased costs. Several stratification schemes have been proposed to improve
      initial antimicrobial selection. These schemes identify patient's age, severity
      of underlying pulmonary dysfunction, frequency of exacerbations, and the presence
      of comorbid illnesses as predictors for likely pathogens and to guide
      antimicrobial selection. This approach may reduce the risk for treatment failure,
      which would have significant medical and economic implications. Improved
      understanding of the roles of airway inflammation and infection in the
      pathogenesis of progressive airway disease, in addition to future studies
      examining the efficacy of newer classes of antimicrobials, should guide
      physicians to target early and effective treatment to high-risk patients.

PMID- 9779385
TI  - Value of noninvasive studies in community-acquired pneumonia.
AB  - Noninvasive diagnostic studies, i.e., sputum gram stain, sputum culture, blood
      culture and antigen detection assays will assist the clinician in the selection
      of initial antimicrobial therapy in some patients. These tests may be even more
      valuable in adjusting treatment regimens to prevent the use of broad spectrum
      antimicrobial agents as routine therapy.

PMID- 9779386
TI  - Invasive diagnostic techniques for pneumonia: protected specimen brush,
      bronchoalveolar lavage, and lung biopsy methods.
AB  - We suggest the following strategy for managing patients with pneumonia. For
      nonventilated patients with either CAP or HAP, empiric antibiotic treatment
      should be started according to approved guidelines, and if the clinical evolution
      of the patient is not adequate, fiberoptic bronchoscopy including PSB and BAL
      could be considered, with modification of the antibiotic treatment accordingly.
      In ventilated patients with either CAP or HAP, respiratory secretion sampling
      using noninvasive techniques should be conducted upon clinical suspicion of VAP
      and before starting a new antibiotic treatment. Antibiotic therapy according to
      approved guidelines should be started as soon as possible and maintained during
      the first 48 hours if the patient's evolution is satisfactory and condition has
      stabilized. Then, initial antibiotic treatment should be adjusted according to
      cultures. If there is a clear diagnostic alternative to VAP and cultures are
      negative, this is the only case in which antibiotic treatment could be withdrawn.
      If the patient's clinical evolution is inadequate (persistence of fever,
      leukocytosis, increasing infiltrates, and respiratory failure), fiberoptic
      bronchoscopy with PSB and BAL and modification of the initial antibiotic regimen
      should be sought. Open lung biopsy may be indicated in patients with diffuse
      pulmonary infiltrates in whom a diagnosis has not been achieved by other methods,
      including bronchoscopy. Transbronchial lung biopsy should not be viewed as a
      diagnostic technique for pneumonia except in immunosuppressed patients with
      diffuse alveolar infiltrates.

PMID- 9779388
TI  - Assessing prognosis and selecting an initial site of care for adults with
      community-acquired pneumonia.
AB  - Over the last 20 years, more than 15 medical practice guidelines and clinical
      prediction rules have emerged to assist physicians in assessing the prognosis of
      adult patients with community-acquired pneumonia (CAP) and selecting an
      appropriately matched initial site of care. Most of these guidelines and rules
      suffer from major methodological flaws. One, the Pneumonia Patient Outcomes
      Research Team (PORT) clinical prediction rule, has satisfied rigorous
      methodological standards for the derivation and validation of high-quality
      prediction rules. This rule was incorporated into the Infectious Disease Society
      of America medical practice guideline for the management of adults with CAP.
      Strengths of the rule include its derivation and validation in over 50,000
      inpatients and outpatients; stratification of all immunocompetent adult patients
      into one of five risk strata for short-term mortality and other unambiguous
      adverse medical outcomes; initial site of care recommendations for all patients,
      particularly those at low risk; and reliance on predictor variables readily
      available to clinicians at the time of initial patient presentation. A recent
      small-scale intervention trial demonstrates that the pneumonia PORT rule can
      reduce admissions for adult patients with CAP without compromising patient
      outcomes.

PMID- 9779387
TI  - Community-acquired pneumonia: epidemiology, etiology, treatment.
AB  - Community-acquired pneumonia is a common and severe illness. S. pneumoniae
      remains the most common cause of CAP; however, more than 100 microbials cause
      this illness. Antibiotic treatment is dictated by the severity of the pneumonia.

PMID- 9779389
TI  - Hospital-acquired pneumonia: epidemiology, etiology, and treatment.
AB  - Despite improvements in diagnosis, treatment, and prevention, hospital-acquired
      pneumonia (HAP) remains the number one cause of nosocomial mortality. This
      article reviews the current knowledge regarding the incidence, epidemiology, and
      causes of HAP, with the appreciation that the available information is incomplete
      and that controversies are common, and thus the authors provide a rational
      approach to the initial management of HAP in immunocompetent adults. A discussion
      of therapy and what to do with patients who do not respond to the empiric therapy
      are included. The American Thoracic Society (ATS) statement on HAP has served as
      a foundation for this review but has been supplemented by newer literature that
      was not available when the ATS statement was developed.

PMID- 9779390
TI  - Pneumonia in the compromised host including cancer patients and transplant
      patients.
AB  - Pneumonia remains a major cause of morbidity and mortality in the
      immunocompromised host. The type and timing of immunosuppression will predispose
      the patient to infections with certain pathogens. This article discusses the
      types of immunosuppression and their infectious and noninfectious implications.
      Key points of the most commonly involved pathogens are mentioned. Finally, an
      approach to diagnosis and empiric therapy is discussed.

PMID- 9779391
TI  - Pneumonia in the patient with HIV infection.
AB  - The lower respiratory tract has always been a major site of complications in
      patients with human immunodeficiency virus (HIV) infection. In the era before
      Pneumocystis carinii prophylaxis (PCP) this organism accounted for more than 70%
      of initial AIDS-defining diagnoses and was by far the most common identifiable
      cause of mortality. Even in the era of prophylaxis, PCP continues to be the most
      common AIDS-defining diagnosis and the most common identifiable cause of death.
      Despite the historic emphasis on PCP, bacterial pneumonia seems to be at least as
      common or more common. A substantial spectrum of other opportunistic pathogens
      are also commonly encountered in these patients. This article reviews pneumonia
      in patients with HIV infection.

PMID- 9779392
TI  - EMG of spinal muscles.

PMID- 9779393
TI  - Ligamento-muscular protective reflex in the lumbar spine of the feline.
AB  - A ligamento-muscular protective reflex in the lumbar spine was demonstrated in a
      feline model. Stimulating electrodes were applied to the supraspinous ligament
      between several lumbar vertebra (L1 to L6) while recording myoelectric discharge
      from the paraspinal muscles at the L3, L4 and L5, bilaterally. Electromyographic
      (EMG) activity was present in the paraspinal muscles bilaterally, upon
      stimulation of the supraspinous ligament, in six preparations. The EMG discharge
      was strongest in the muscles one level below that of the stimulated ligament,
      whereas weaker EMG signals were recorded from as far as two levels above and
      below. The mean time delay between the application of the stimulus to the
      ligament to the resulting EMG ranged from 2.52 to 2.77 ms at all levels.
      Stimulation of the supraspinous ligament in the L6 segment resulted in a weak
      reflex response, and stimulation in the L7 segment did not produce any EMG
      activity. It was concluded that mechanoreceptors in the supraspinous ligament at
      the L1/6 levels may initiate sensory signals upon strain of the ligament, during
      flexion. This, in turn, causes contraction of the paraspinal muscles,
      bilaterally, to extend the spine and prevent possible damage to the ligament
      while maintaining stability. The results may add to the understanding of low back
      pain, and to the formulation of surgical procedures which could spare the neural
      supply of the ligament, allowing advanced physiotherapeutic modalities to be
      implemented for post-surgical rehabilitation.

PMID- 9779394
TI  - EMG recordings of abdominal and back muscles in various standing postures:
      validation of a biomechanical model on sacroiliac joint stability.
AB  - In a biomechanical model we described that for stability of the flat sacroiliac
      joints (SIJ) muscle forces are required which press the sacrum between the two
      hip bones (self-bracing). Shear loading of these joints is caused by gravity and
      longitudinally oriented muscles. Protection against shearing can come from
      transversely oriented muscles like the internal oblique (OI) abdominal muscles.
      For validation we used standing postures with significantly more or less OI
      activity compared to activity in a standardized erect standing reference posture.
      OI activity decreased significantly when (a) resting on one leg (the
      contralateral), as can be observed at bus stops, (b) tilting the pelvic backward
      and (c) applying a pelvic belt. We explain this decrease of OI activity by,
      respectively, decrease of gravity load, decrease of load from the psoas major
      muscles, and a substitute of self-bracing. The outcome of this study is in line
      with the biomechanical model on SIJ stability. Clinical relevance of this study
      regards aspecific low back pain and is found in the effect of the use of a pelvic
      belt, of a trunk position as adopted when wearing a small rucksack and of the
      benefit of exercising trunk muscles in extension and torsion.

PMID- 9779395
TI  - Trunk kinematics and trunk muscle activity during a rapidly applied load.
AB  - This study investigated the trunk kinematics and electromyographic (EMG) activity
      of eight trunk muscles when "expected" and "unexpected" loads were applied
      directly to the torso. Twenty individuals (mean age: 25.1 yr; range 20-33 yr)
      participated in this mixed model study in which gender was the between-subjects
      factor, and expectancy and symmetry of the applied load were within-subject
      factors. The sudden load was delivered to the subject via a cable attached to a
      thoracic harness and motion was restricted to the lumbar spine by strapping the
      pelvis to a rigid fixation apparatus. Surface EMG was recorded bilaterally from
      the longissimus thoracis (LGT), erector spinae (ERS), rectus abdominis (RAB) and
      the external obliques (EXO). Trunk kinematics were measured with a Lumbar Motion
      Monitor. During expected loading conditions, the peak muscle activity was reduced
      for the RAB and EXO bilaterally, and for the ERS(R) (p < 0.01) relative to the
      unexpected conditions. Conversely, the normalized area of EMG activity prior to
      the onset of load was increased for the ERS and EXO bilaterally, and for the
      RAB(R) (p < 0.05) during an expected loading event. Trunk motion in the sagittal
      and frontal planes was reduced during expected loading. Activation of the trunk
      muscles just prior to a rapid loading event increases trunk stiffness, decreasing
      trunk displacement and peak muscle activity.

PMID- 9779396
TI  - Frequency response of spine extensors during rapid isometric contractions:
      effects of muscle length and tension.
AB  - During muscle contraction, electrical activity necessarily precedes force output,
      yet models that utilize processed electromyograms sometimes predict force as
      preceding EMG under rapid ballistic loading conditions. The purpose of this study
      was to define the frequency response transfer function of the upper and lower
      erector spinae musculature, at different lengths and tensions, using rectified,
      low pass filtered EMG. This would enable accurate estimates of force from the
      processed electromyogram, specifically during impulsive contractions. Abdominal
      and erector spinae EMG were measured in synchrony with impulsive low back moments
      in five men. EMG signals were rectified and low pass filtered repeatedly with cut
      off frequencies from 1 to 3 Hz at 0.5 Hz increments in order to quantify the
      frequency response. It was found that EMG signals processed through a simple,
      Butterworth low pass filter could not produce the measured force output without
      an additional time shift. These shifts were quantified by cross-correlating EMG
      and force with increments of 1 ms. In order to define the transfer function of
      EMG to force, optimal cut-off frequencies were selected two ways: quantitatively
      by searching for maximum cross correlations coefficients, and qualitatively.
      Results indicated that the frequency response of both the upper and lower erector
      spinae can be modelled with a cut-off frequency between 2 and 2.5 Hz and that
      these values are not significantly modulated by changes in muscle length or
      tension.

PMID- 9779397
TI  - EMG assessment of back muscle function during cyclical lifting.
AB  - A new approach to estimating the frequency compression of the surface EMG signal
      during cyclical dynamic exercise is described. The basic properties of the method
      are first developed using simulated EMG signals. Spectral compression is measured
      by defining the instantaneous median frequency from time-frequency
      representations of the signal derived from a transformation of the Cohen class.
      The technique is then used to process real EMG signals from paraspinal muscles
      during repetitive lifting. Our purpose was to use this new procedure to identify
      (a) whether changes in the instantaneous median frequency among concurrently
      active paraspinal muscles during repetitive trunk extension produces a 'fatigue
      pattern' that is indicative of normal functioning, and (b) whether this pattern
      is different when the subject produces a sustained isometric trunk extension.
      Four healthy subjects (26 +/- 4 years; 3 males, 1 female) were tested in both a
      Back Analysis System, for the production of a sustained static isometric
      contraction, and a LIDO-Lift Controller (Loredan), for repetitive lifting and
      lowering of a weighted box. EMG signals were recorded concurrently from six
      bilateral lumbar paraspinal regions during these tasks. The results demonstrate
      that static and dynamic tasks result in very different patterns of EMG spectral
      changes, suggestive of differences in load-sharing and underlying metabolic
      fatigue processes. Unlike the linear decrease in median frequency observed for
      static contractions, during dynamic contractions instantaneous median frequency
      behavior is non-linear and more complex. Examples are provided in which distinct
      periods of instantaneous median frequency decay are followed by periods of
      recovery during a single trial of repetitive lifting. It is hypothesized that
      this difference reflects a complex strategy of utilizing muscle load-sharing
      during strenuous dynamic exercise to provide periods of metabolic recovery that
      limit localized fatigue. New analysis procedures to characterize this complex
      behavior are needed to enhance the technique for assessment of impairment in
      patients with lower back pain.

PMID- 9779398
TI  - Trunk muscle activities during asymmetric twisting motions.
AB  - Axial twisting of the torso has been identified via epidemiologic studies as a
      significant risk factor for occupationally-related low back disorders. However,
      only recently have biomechanical studies been able to describe how twisting is
      accomplished through the use of the trunk musculature. These studies have been
      performed on subjects whose torso twists were performed in an upright posture. In
      this study, the electromyographic activity of ten trunk muscles was observed
      while 12 subjects performed twisting exertions in three different trunk postures.
      These postures included upright twisting, twisting while the trunk was flexed in
      the sagittal plane, and twisting while the trunk was flexed and rotated
      asymmetrically. In addition, twisting velocity and direction of motion were
      changed under the experimental conditions. Under upright twisting conditions, the
      twisting torque was generated easily and relatively efficiently through the
      employment of the oblique (internal and external) and latissimus dorsi muscles.
      When the trunk was flexed the activity of erector spinae muscles increased (about
      10-15%) while the external oblique activity decreased (about 3-5%). Twisting
      while in asymmetric bent postures was accomplished with a reduction in oblique
      and latissimus dorsi muscle activities (approximately 5%) while the erector
      spinae muscle activity remained elevated. The change in muscle activity needed to
      balance the torso during twisting while bending also increased the amount of
      lateral torque that was produced by the trunk. These findings suggest that
      studies observing trunk muscle activities and trunk loading while subjects were
      in upright postures should be interpreted with caution when evaluating the
      activity of the trunk during occupational activities. Since many occupational
      twisting tasks are performed in awkward, asymmetric postures, application of
      results from upright twisting studies might underestimate the risk of these
      activities.

PMID- 9779399
TI  - Spectral parameters of trunk muscles during fatiguing isometric axial rotation in
      neutral posture.
AB  - Axial rotation of the trunk is commonly associated with back injury and pain.
      However, the behaviour of trunk muscles in axial rotation is poorly understood.
      The objective of this study was to measure spectral parameters from the EMG of
      erector spinae at T10 and L3 levels, latissimus dorsi, external and internal
      oblique, rectus abdominis and pectoralis major muscles bilaterally in a
      standardized repeatable axial rotation at 60% MVC to fatigue. Twelve young and
      healthy subjects were recruited after screening for musculoskeletal disorders.
      Surface electrodes were applied to the named seven trunk muscles bilaterally.
      Subjects were seated in the device called Axial Rotation Tester and stabilized
      such that they could rotate only their thoracolumbar spine. Other motions were
      prevented. Subjects held 60% of their MVC for a period of 2 min. Samples (2.1 s)
      were obtained at every 10 s interval at a sampling frequency of 1 KHz. Samples
      were subjected to FFT analysis. The total power and the median frequencies were
      analyzed. The median frequency for different muscles were different (p < 0.001).
      The slopes of decline of the median frequencies of the agonists were different
      for different muscles (p < 0.001). This differential fatiguing rate could
      conceivably create a force imbalance potentiating back injury.

PMID- 9779400
TI  - Evaluation of EMG signals from rehabilitated patients with lower back pain using
      wavelets.
AB  - This paper reports the preliminary results of an analysis of surface EMG signals
      obtained from rehabilitated patients with lower back problems using discrete
      wavelet transform techniques. In our study, 12 patients with lower back pain were
      tested before and after rehabilitation. The reaction time difference (before and
      after rehabilitation) from the erector spinae muscle caused by sudden loading was
      determined. The results indicated that the reaction time after rehabilitation was
      shorter than that before rehabilitation for about 45% of the tested cases.

PMID- 9779401
TI  - The risk of teen mothers having low birth weight babies: implications of recent
      medical research for school health personnel.
AB  - This article reviews recent medical research on the relationship between young
      maternal age and the incidence of low birth weight infants. One line of research,
      "nature," emphasizes biological factors in early adolescence such as immaturity
      of the female reproductive system and inadequate prenatal weight gain. "Nurture,"
      another research focus, stresses sociocultural attributes of teen mothers such as
      poverty and minority status. Young maternal age alone does not explain the higher
      rates of low birth weight infants born to adolescent females. Both biological and
      sociocultural factors, plus lifestyle choices made by adolescents, combine to
      raise or lower the risk of delivering a low birth weight infant. School health
      personnel need to link their health promotion efforts to those of other community
      organizations serving adolescents and their families.

PMID- 9779402
TI  - Statewide assessment of school-age children with asthma in Delaware.
AB  - In Delaware, asthma affects almost 14,000 children. The American Lung Association
      of Delaware and the University of Delaware surveyed school nurses to identify the
      needs of children with asthma and the services and accommodations available for
      these children. Researchers developed a survey instrument that was mailed to all
      Delaware schools (N = 324). The response rate was 38.6% (n = 125). According to
      respondents, a variety of protocols were in place regarding the administration of
      asthma medications. Respondents also reported that several measures had been
      taken to modify the school environment to improve air quality and reduce asthma
      triggers. Most respondents (77%) indicated they did not have asthma education
      programs in their schools. Findings from this study sparked development of a
      multidisciplinary Delaware Asthma Committee, an Asthma Education Center, and a
      statewide system for communicating with the parents of children with asthma.

PMID- 9779403
TI  - Evaluation of Jump Into Action: a program to reduce the risk of non-insulin
      dependent diabetes mellitus in school children on the Texas-Mexico border.
AB  - Jump Into Action, a school-based non-insulin dependent diabetes mellitus (NIDDM)
      prevention program, encourages students to eat low-fat foods and exercise
      regularly to reduce their risks for developing NIDDM. A study was conducted in a
      school district with a predominately Hispanic enrollment to assess the
      effectiveness of Jump Into Action in improving fifth-graders' knowledge, self
      efficacy, and behaviors regarding NIDDM prevention. Jump Into Action was found
      effective in increasing knowledge and self-efficacy regarding NIDDM prevention
      and improving dietary and exercise-related behaviors. These gains were sustained
      from posttest to follow-up four weeks later.

PMID- 9779405
TI  - Emerging concepts of health and health promotion.

PMID- 9779406
TI  - Distract me from my dreaded self: strategies to enhance self-esteem.

PMID- 9779404
TI  - Junior high school students' perceptions regarding nonconsensual sexual behavior.
AB  - This study assessed early adolescents' attitudes and perceptions regarding
      nonconsensual sexual activity. A total of 371 surveys (94% return rate) was
      completed. More than one-third of respondents (35%) reported they had engaged in
      sexual intercourse; 17% reported having been sexually coerced by a teen-ager; 19%
      reported feeling pressure from their friends to have intercourse; 7% reported
      having been sexually coerced by an adult; and 6% reported having sexually coerced
      someone else. Students also demonstrated lack of knowledge regarding
      nonconsensual sexual behaviors. Analysis of variance tests determined if
      knowledge (KN), attitudes (AT), behavioral intentions (BI), and locus of control
      (LC) changed across specific background and demographic variables. One background
      variable (having been sexually coerced by a teen-ager) was associated with high
      risk orientation (lower scores) on all four subscales. Lower scores also were
      associated with being male (KN, AT, BI), having sexually coerced someone else
      (KN, AT, BI), having been sexually coerced by an adult (AT, BI), and having
      engaged in sexual intercourse (AT, BI).

PMID- 9779407
TI  - Assessing rural community viewpoints to implement a school-based health center.

PMID- 9779408
TI  - Video display terminals: safe use guidelines.

PMID- 9779409
TI  - Tree-type algorithm for statistical analysis in chronic toxicity studies.
AB  - An appropriate statistical methodology in toxicity studies has been discussed
      over the last two decades and many statistical methods have already been
      proposed. Many practical problems, however, still remain unresolved and most
      pharmaceutical industries have been using a tree-type algorithm routinely to
      analyze repeated-dose toxicity study data. In considering routine use of
      statistical analysis in toxicological studies, standardization of statistical
      methodology is necessary and the decision tree has an important role. In this
      article, the problems, relating to tree-type algorithms are summarized. Then we
      propose a new tree-type algorithm, which targets quantitative data in repeated
      dose studies in rodents, usually sample size per group between 10 to 20, based on
      the following two important principles: "using a parametric method" and "suitable
      for intuition of toxicologists". An example of its application to actual toxicity
      study data is demonstrated. The performance of this new method is also evaluated
      using historical data. However, it should be noted that the intention of this
      paper is not to make a definite solution of the decision tree. Several other
      alternatives can be considered. Since there is no single theoretically correct
      solution of tree-type algorithms, too formal a use of the decision tree is not
      recommended. We must not forget the exploratory nature of evaluating repeated
      toxicity data.

PMID- 9779410
TI  - Correlation between NO-induced ATP depletion and cytotoxicity in PC12 cells.
AB  - To ascertain whether NO-elicited cell death is mediated by decreased
      intracellular ATP, the effect of sodium nitroprusside (SNP), a NO-generator, on
      ATP content in PC12 cells was examined. After treatment with SNP, the ATP content
      in PC12 cells was found to decline in a time- and concentration-dependent manner.
      The decline of ATP content in PC12 cells caused by SNP was found to occur before
      the appearance of cytotoxicity estimated by MTT staining. In addition, the ATP
      content of neuronally differentiated PC12 cells, which has been shown to have a
      higher resistance to SNP than the undifferentiated cells (Nakamura et al., 1997),
      was less affected by SNP treatment than the undifferentiated cells. These
      findings suggest that reduction of intracellular ATP content may be one of the
      mechanisms responsible for the NO toxicity in PC12 cells.

PMID- 9779411
TI  - Cellular size of bone marrow cells from rats and beagle dogs.
AB  - The usefulness of cellular size measurement for differentiating erythroid and
      myeloid cells was investigated using rat and canine bone marrow film prepared by
      the Cytospin method and Wright-Giemsa staining. 1. In the erythroid series,
      basophilic and polychromatic erythroblasts were distinguishable in terms of
      cellular diameter; i.e., 99% of rat and 95% of canine polychromatic erythroblasts
      were distributed in a range < or = 9.5 microns, at which basophilic erythroblasts
      did not exist. 2. In the myeloid series, myelocytes and metamyelocytes were to
      some extent distinguishable by their diameters; in rats, myelocytes (75% of the
      population) were > or = 13.5 microns, and metamyelocytes (61%) < or = 11 microns;
      and in dogs, myelocytes (45%) were > or = 16 microns, and metamyelocytes (66%) <
      or = 12 microns. 3. With regard to the metamyelocytes and myelocytes existing in
      the same range, their nuclear sizes (width) allowed further differentiation; in
      rats, the nuclear width of myelocytes (87%) was > or = 5 microns, and that of
      metamyelocytes (84%) < 5 microns; and in dogs, myelocytes (96%) > or = 7 microns,
      and metamyelocytes (88%) < 7 microns. The present results indicate that cellular
      size, together with nuclear size, contribute to distinguish the active mitotic
      group from less- or non-mitotic group in erythroids and myeloids, thus being
      helpful for toxicological evaluation on chemicals.

PMID- 9779412
TI  - Reversible irritative effect of acute 2.45GHz microwave exposure on rabbit eyes-
      a preliminary evaluation.
AB  - We have attempted to determine if there is a hazardous effect of acute microwaves
      at 2.45 GHz on the eye of a rabbit under lengthy exposure without anesthesia, the
      contralateral eye serving as a control. Unilateral eyes of 9 adult Japanese white
      rabbits (10-12 weeks of age) were irradiated by 2.45 GHz continuous wave (CW)
      microwave for 160 min. to 240 min. under restraint without anesthesia. The
      specific absorption rate (SAR: phantom material) was 26.5 W/kg. The corneal
      surface temperature increment was 3.0 degrees C for 15 min. on average. Miosis
      occurred in all rabbits within 15 min. Post-exposure ophthalmological signs,
      first detected as the effect of CW irradiation, included 1) miosis and pupillary
      congestion; 2) keratoleucoma and corneal edema; 3) endothelial cell detachment
      and floating in aqua oculi, 4) fibrinogenesis in the anterior chamber, and 5)
      conjunctiva edema, which disappeared one week after exposure. There was no
      cataract formation. The acute microwave irradiation to the rabbit eye, causing
      the miosis and pupillary congestion in all irradiated eyes, was the first to be
      detected.

PMID- 9779414
TI  - Immunohistochemical studies of TSH-producing cells in the pituitary and
      expression of growth factors in thyroidal proliferative lesions in rats treated
      with thiourea and excess vitamin A.
AB  - Changes of TSH-producing cells in the pituitary and thyroid expression of the
      growth factors, transforming growth factor alpha (TGF alpha) and epidermal growth
      factor receptor (EGFR), as well as cyclin D1, were investigated
      immunohistochemically in order to clarify their contribution to the enhancing
      effects of excess vitamin A (VA) on thyroidal carcinogenesis induced by thiourea
      (TU). Male rats were allocated to 4 groups, control, TU, VA, and TU + VA,
      respectively, receiving no treatment, water containing 0.2% TU, diet containing
      0.1% VA, and both for 10 or 19 weeks after a single s.c. injection of DHPN (2800
      mg/kg) for initiation. Immunohistochemistry using antibodies against TSH
      demonstrated enlargement of TSH-producing cells in the TU + VA group as compared
      to the TU group, supporting our conclusion that enhanced TSH stimulation is
      mainly responsible for promoting the effects of excess VA. Since the expression
      of TGF alpha, EGFR, and cyclin D1 in thyroid proliferative lesions did not
      exhibit any differences between the TU and TU + VA groups in the present study,
      these factors are unlikely to participate in VA enhancement of carcinogenesis.

PMID- 9779415
TI  - Mepanipyrim induces fatty liver in rats but not in mice and dogs.
AB  - Mepanipyrim, a new fungicide, was administered orally to rats, mice and dogs for
      13 weeks to clarify its toxic profiles. Hepatotoxicities were observed
      characteristically in these species with high concentrations of mepanipyrim; more
      than 200 ppm in rats, more than 1,000 ppm in mice, and more than 50 mg/kg/day in
      dogs. In rats, obvious fatty vacuolation in the perilobular hepatocytes and
      changes in the serum-lipid concentrations such as total cholesterol (TC),
      triglyceride (TG), phospholipid (PL) and non-esterified fatty acid (NEFA) were
      observed. This fatty liver appeared to be based on the alteration of lipid
      metabolism. In contrast, no remarkable changes were observed in mice and dogs
      except for an enhancement of anisonucleosis in mice or a lipofuscin deposition in
      Kupffer cells and hepatocytes in dogs. It appeared that there were species
      differences in the hepatotoxicities of mepanipyrim.

PMID- 9779416
TI  - Effects of mepanipyrim on lipid metabolism in rats.
AB  - Our preceding paper reported that mepanipyrim, a new fungicide, induced fatty
      liver in the rat. This study was undertaken to examine this phenomenon further on
      hepatic triglyceride (TG) synthesis, on liver and serum lipid concentrations, and
      on concentration of serum very-low-density lipoprotein (VLDL) in rats fed for 3
      weeks on the drug at 4,000 ppm. Mepanipyrim decreased the incorporation of 14C
      acetate into hepatic TG, total cholesterol (TC) and total lipids. In addition,
      mepanipyrim treatment induced a drastic increase in hepatic TG accompanying a
      decrease in serum TG. Esterified cholesterol (CE), phospholipid (PL) and non
      esterified fatty acid (NEFA) also increased in the liver with a concomitant
      decrease in the serum. The decrease of serum VLDL by mepanipyrim was comparable
      to the decrease in serum TG. Because hepatic TG is secreted into the blood by
      forming VLDL, which consists of TG, TC, PL, and apoprotein, the decrease in serum
      TG would be mainly ascribable to that in serum VLDL. Mepanipyrim also decreased
      serum concentrations of low-density lipoprotein (LDL) and high-density
      lipoprotein (HDL), and the relative weights of the epididymal adipose tissue,
      indicating that a reduction in serum VLDL does not reflect acceleration of serum
      VLDL dissimulation. These results suggest that the fatty liver induced by
      mepanipyrim would be due to the inhibition of hepatic VLDL synthesis or its
      secretion into the blood.

PMID- 9779413
TI  - Occurrence of toxicity and cell proliferation after a single gavage
      administration of chloroform to male F344 rats.
AB  - Chloroform, an industrial solvent and one of the most common environmental
      contaminants which produces carcinogenic effects in the liver and kidney of
      rodents, is not genotoxic in most traditional bacterial and mammalian test
      systems. Its carcinogenic potential appears attributable to the sustained cell
      turnover (regenerative hyperplasia) which results from chronic chloroform
      toxicity. In this present study, cell proliferation (replicative DNA synthesis,
      RDS) and histopathological changes in hepatocytes and renal tubular epithelial
      cells were assessed in male F344 rats following a single gavage chloroform
      exposure (50, 150 or 500 mg/kg). In addition, biochemical parameters (BUN, GOT,
      LDH and NAG) were examined using plasma and urine samples. Cell proliferation and
      histopathological changes (e.g. hypertrophy, necrosis, vacuolation) were only
      seen at the dose of 500 mg/kg in the liver and kidney. At the same dose, all
      biochemical markers were increased at the 24 to 48 hr time points. These results
      obtained are thus in line with earlier findings pointing to epigenetic
      carcinogenicity.

PMID- 9779417
TI  - Cadmium accumulation in rats treated orally with cadmium chloride for 8 months.
AB  - To investigate the accumulation pattern of cadmium (Cd) in the liver and kidney
      following Cd intake from diet, female SD rats were fed cadmium chloride (CdCl2)-
      contained diets (1.24 and 4.96 ppm Cd) for 2 or 4 months. The other rats were fed
      CdCl2-contained diets (8, 40, 200, and 600 ppm Cd) for 2, 4 or 8 months. The
      control rats were given diet without Cd addition (lower than 0.01 ppm Cd). The
      concentrations of Cd in the liver and kidney derived from all rats were
      determined. The concentrations of Cd in the liver and kidney increased depending
      on the dosage of Cd. The concentrations of Cd in the liver did not reach plateau
      level even in the 200 and 600 ppm groups. On the other hand, the concentrations
      of Cd in the kidney in the 200 and 600 ppm groups reached a plateau level, which
      was approximately 250 micrograms/g. In the 600 ppm group, the concentrations of
      Cd in the kidney reached 250 micrograms/g at 2 months, but did not exceed that
      level at 4 months. In the 200 ppm group, the concentrations of Cd in the kidney
      increased to nearly the level of 250 micrograms/g at 8 months. The ratio of the
      concentrations of Cd in the kidney versus liver decreased as the dosage of Cd
      increased, suggesting that a low dosage of Cd was distributed preferentially to
      the kidney, but a high dosage of Cd was distributed to the liver. The relation
      curves between total amounts of Cd intake and Cd levels in the kidney in the 2-,
      4-, and 8-month groups showed a parabola. The curves were shifted in parallel in
      the direction of higher levels of ingested Cd in order of length of Cd exposure
      period. These results suggested that when Cd is ingested over a long time at low
      concentrations, the amount of Cd accumulation in the kidney is small even for
      equal amounts of total ingested Cd.

PMID- 9779418
TI  - Long-read direct infrared sequencing of crude PCR products for prediction of
      resistance to HIV-1 reverse transcriptase and protease inhibitors.
AB  - Patients infected with human immunodeficiency virus type 1 (HIV-1) are being
      treated with a number of different combinations of antiretroviral compounds that
      target the essential viral enzymes reverse transcriptase and protease. Different
      sets of HIV-1 mutations that confer drug resistance have been well defined; they
      allow reasonable prediction of the drug sensitivity pattern from analysis of the
      HIV-1 genotype in vivo. Since periodical monitoring of genotypic resistance is
      expected to improve clinical management in a large number of infected patients,
      practical and cost-effective methods are highly desirable to set at least medium
      scale sequencing in clinical diagnostic settings. We present a complete protocol
      for direct sequencing of HIV-1 reverse transcriptase and protease-coding regions.
      Features making the system amenable to routine clinical use include: 1. Highly
      robust presequencing steps (plasma RNA extraction, reverse transcription, and
      nested PCR); 2. Direct use of the crude unpurified PCR product as the sequencing
      template; and 3. Use of infrared-labeled sequencing primers consistently allowing
      long reads, thus obviating the need for sequencing of both DNA strands.

PMID- 9779419
TI  - A study of the interactions between an IgG-binding domain based on the B domain
      of staphylococcal protein A and rabbit IgG.
AB  - The nonantigenic interaction between a recombinant immunoglobulin G (IgG)-binding
      protein based on the B domain of Protein A from Staphylococcus aureus (termed
      SpA1) and the Fc fragment of rabbit IgG has been investigated. The contribution
      to binding of four putative hydrogen bond contacts between SpA1 and IgG-Fc were
      examined by the individual substitution of the residues in SpA1 involved in these
      interactions by others unable to form hydrogen bonds. It was found that the most
      important of the hydrogen bonds involved Tyr 18 which, when replaced by Phe,
      resulted in a twofold decrease in IgG-binding affinity. The residues of SpA1
      proposed to make close, mainly hydrophobic, contacts with Fc were replaced by
      residues with potential electrostatic charge to establish the importance of the
      hydrophobic interaction in the complex. The IgG-binding affinities of the mutant
      proteins were compared to the wild-type protein by a competitive enzyme-linked
      immunosorbent assay. The replacement of individual hydrophobic residues by His
      generated a number of novel IgG-binding proteins with reduced binding affinity at
      pH 5.0 but which maintained strong binding affinities at pH 8.0. The elution
      profile of human IgG1-Fc (Fc fragment of human IgG1) from a column made from an
      immobilized two-domain mutant protein shows that the complex dissociates at a
      higher pH relative to that of the non-mutated protein thus offering favorable
      elution characteristics.

PMID- 9779420
TI  - Rapid establishment of high-producing cell lines using dicistronic vectors with
      glutamine synthetase as the selection marker.
AB  - Recombinant proteins are useful tools in biological research, drug development,
      and drug screening. Specially designed expression vectors have been developed to
      introduce cDNA for recombinant protein expression in mammalian cells. We have
      combined a dicistronic mRNA design for expression of the recombinant protein,
      using glutamine synthetase (GS) for selection. A soluble form of human
      interleukin-4 receptor alpha chain was used as the model protein. The dicistronic
      vectors were compared to a standard expression vector in CHO-K1 cells in parallel
      experiments. Our data showed that a dicistronic vector containing an internal
      ribosome entry site (IRES) of the encephalomyocarditis virus (ECMV) was superior
      to a conventional expression vector in both levels of protein expression and
      amplification efficiency. The productivity of these clones was stable without
      selection pressure for an extended period of time. The GS selection system within
      a dicistronic vector design can achieve rapid and efficient gene amplification
      for protein production.

PMID- 9779422
TI  - In situ localization of PCR-amplified DNA and cDNA.
AB  - Combining the high sensitivity of PCR with the cell localizing ability of in situ
      hybridization allows for the reproducible detection of low copy targets in intact
      cells. This article describes several key variables that include fixation,
      protease digestion, the hot start maneuver, stringency, and, for RNA analysis,
      DNase digestion that are important to successful in situ PCR. Also stressed is
      the importance of performing and interpreting controls with each experiment.
      Important controls include omission of key components, use of samples known
      either to contain or lack the target of interest and, most importantly, the in
      built controls invariably present in the heterogeneous component of any given
      tissue type.

PMID- 9779423
TI  - An in vitro transcription assay for probing drug-DNA interactions at individual
      drug sites.
AB  - An in vitro transcription assay of drug-DNA interactions has been described and
      is based largely on the stable lac UV5-initiated transcription complex. This
      system utilizes a synchronized population of radiolabeled nascent RNA 10
      nucleotides long. Reaction of this initiated transcription complex with drug and
      subsequent elongation of the nascent RNA by Escherichia coli RNA polymerase,
      reveals blockages at drug binding sites. From these blockages it is possible to
      obtain four features of the drug-DNA interaction: the sequence of preferred drug
      binding sites, the relative drug occupancy at each binding site, the drug
      dissociation rate at each site, and the probability of drug-induced termination
      of transcription at each site. The unidirectional transcription assay has been
      extended to a two-promoter, counter-directed system, which yields a bidirectional
      transcription footprint of drug sites.

PMID- 9779421
TI  - Computational methods for exon detection.
AB  - Computer methods for the complete and accurate detection of genes in vertebrate
      genomic sequences are still a long way to perfection. The intermediate task of
      identifying the coding moiety of genes (coding exons) is now reasonably well
      achieved using a combination of methods. After reviewing the intrinsic
      difficulties in interpreting vertebrate genomic sequences, this article presents
      the state-of-the-art, with an emphasis on similarity search methods and the
      resources available through Internet.

PMID- 9779424
TI  - Selective differential fingerprinting. A method for identifying differentially
      expressed genes in a family between two samples.
AB  - A method termed selective differential fingerprinting (SDF) has been developed
      that enables one to investigate the level of expression for a family of genes
      between two samples. SDF produces a fingerprint (on a sequencing gel) on reverse
      transcription polymerase chain reaction (RT-PCR) of a sample with degenerate
      primers designed from conserved regions of a family of genes. By comparing
      fingerprints obtained after SDF with primers representing the transforming growth
      factor-beta (TGF beta) family of growth factors between a low-grade and a high
      grade tumor from the same patient, a TGF beta family member known as osteogenic
      protein 1 (OP-1) or bone morphogenic protein 7 (BMP-7) was found to be greatly
      overexpressed in the high-grade tumor compared to the low-grade one. SDF also has
      the potential to identify novel genes. SDF offers a general way to identify
      differentially expressed genes for a family between two given samples.

PMID- 9779425
TI  - A simple method to enrich mRNA from total prokaryotic RNA.
AB  - Isolation of prokaryotic mRNA by the poly(dT) method has been difficult,
      primarily due to the great instability of the poly(A) sequence in its mRNA. We
      developed a simple method to remove rRNA from total RNA of Staphylococcus aureus
      by cloning a PCR-amplified S. aureus rRNA gene fragment into a plasmid, and then
      synthesizing biotin-labeled antisense rRNA to subtract rRNA. By using this
      method, S. aureus rRNA is significantly reduced and mRNA is enriched. This method
      may be used to prepare prokaryotic mRNA for many molecular biology applications.

PMID- 9779426
TI  - [Instability of the shoulder region].

PMID- 9779427
TI  - [Histopathological findings in the proprioception of the shoulder joint].
AB  - Purpose of this study was the evaluation of distribution and morphology of
      mechanoreceptors in the glenohumeral joint capsule and rotator cuff in comparison
      to the coracoacromial ligament by means of specific immunfluorescence microscopy.
      The complemente joint capsules, rotator cuffs and coracoacromial ligaments of
      three fresh cadaver shoulder were harvesed. Serial cryostate sections were taken
      and alternately incubated with antiserum against neurofilament, lamin or myelin
      of peripheral nerves. The antibody-reaction was visualized with fluorescin lg-G.
      The nerve endings were photographed and computer-aided 3-dimensional
      reconstructions were performed. Three types of corpuscular and free nerve endings
      of different morphology were found in different distributions: whereas the
      Ruffini corpuscles were much more frequent in the coracoacromial ligament and
      rotator cuff, Pacini endings were predominantly found in the joint capsule.
      Generally corpuscular nerve endings were more frequent in the coracoacromial
      ligament and the rotator cuff than in the antero-inferior capsule and the number
      of corpuscles increased from medial to lateral within the anterior and inferior
      parts of the capsule. The dense ligamentous tissue was almost aneural whereas the
      periarticular fatty or loose connective tissue contained nerve fibres and nerve
      endings. In view of the results of other experimental and clinical studies the
      high frequency of Ruffini and Pacini endings in the rotator cuff and
      coracoacromial ligament suggest, that both are involved in the neurosensory
      control of glenohumeral stability and subacromial impingement. In contrast our
      findings in the joint capsule do not clearly prove, that those joint receptors
      predominantly maintain joint stability.

PMID- 9779428
TI  - [Arthroscopic shoulder stabilization. Differentiated treatment strategy with
      Suretac, Fastak, Holmium: YAG-laser and electrosurgery].
AB  - The goal for arthroscopic stabilization of anterior glenohumeral instability is
      to achieve an outcome equivalent to or better than open procedures. A number of
      arthroscopic procedures have been advocated to reestablish continuity of the
      inferior glenohumeral ligament complex (IGHLC) with the glenoid. Implantable
      suture anchors were developed to avoid the problems associated with arthroscopic
      staple capsulorrhaphy like iatrogenic injury of the glenoid or humeral surface,
      loosening and migration of the staple. Several transosseous techniques include
      the need for an accessory posterior incision, the possibility of neurovascular
      injury (Suprascapular or axillary nerve), and the loosening of the repair after
      typing over the fascia of the infraspinatus posteriorly. The preferred techniques
      are cannulated, absorbable fixation device (Suretac) and easy implantable suture
      anchors made of titanium (Fastak). Even in the hands of experienced
      arthroscopists, unacceptably high recurrence rates for arthroscopic shoulder
      stabilization have been reported, due to the steep learning curve for both
      technical performance and patient selection. Our experience suggests, that if
      proper selection criteria are employed, normal patients and overhead-athletes may
      benefit from the advantages of an arthroscopic repair without accepting an
      increased risk for recurrence. We performed a prospective analysis of 105
      shoulders, who underwent arthroscopic stabilization with Suretac or Fastak
      between 4/96 and 7/98. 48 shoulders were available for followup at least one
      year. The redislocation rate was 6.25% (3 shoulders) and the rate of subluxation
      without dislocation also was 6.25%, but none of the shoulders required a second
      open stabilization. The reason for redislocation or subluxation were 5/6
      traumatic injuries, participating in contact sports or in one case a generalized
      ligamentous laxity. In combination with the LACS-Procedure or the Electro
      thermally assisted capsular shift (ETACS) not only the capsular detachment but
      also the capsular redundancy may be adressed and a lower failure rate can be
      expected.

PMID- 9779429
TI  - [Arthroscopic extra-articular Bankart procedure].
AB  - The arthroscopic extraarticular Bankart procedure tries to imitate the open
      Bankart procedure. An anterior-inferior transmuscular approach through the
      subscapular muscle permits to implant self-locking tacks into the anterior
      inferior third of the glenoid rim. The extraarticular location of the implants
      makes a superomedial capsular shift possible, if required. A total of 257
      arthroscopic repairs following traumatic recurrent anterior shoulder dislocation
      have been carried out between 1992 and 1996. 177 patients were treated only with
      bioabsorbable Suretac device. Clinical and radiological follow up was possible in
      165 patients. According to the Rowe score 69.7% were classified as excellent,
      10.9% as good, 9.7% fair and 9.7% poor. Postoperative complications: the
      recurrence rate was 9.7%, allergic reactions representing a foreign body reaction
      to the synthetic material were seen in 5 cases (3%) and a frozen shoulder in 6
      cases 3.6%). 61% of the patients involved in overhead or contact sports returned
      to their preoperative sport activities.

PMID- 9779430
TI  - [Posterior shoulder joint instability. Classification, pathomechanism,diagnosis,
      conservative and surgical management].
AB  - The posterior instability of the shoulder is a more difficult diagnostic and
      therapeutic challenge than the anterior instability. There are many etiologies
      and causes of posterior instability. Most studies in the literature are
      retrospective and yield a great variation in therapeutic recommendations.
      Generally it has to be separated in traumatic and atraumatic instabilities. Most
      of the traumatic dislocations are impaction fractures of the humeral head against
      the dorsal glenoid. Therapy is depending on the size of the humeral defect, the
      duration of dislocation and the functional demand of the patient. Therapeutic
      possibilities are closed reduction and fixation with a cast, open reduction and
      the transfer of the lower tubercule (McLaughlin's procedure), lifting of the
      defect and supporting with cancellous bone, subcapital rotational osteotomy or
      arthroplasty. The therapy of choice for atraumatic instability is a
      individualized rehabilitation program with strengthening and balancing of rotator
      cuff muscles and scapular stabilizers. Psychologic abnormalities and emotional
      problems have to be recognized prior to any operative procedure. These patients
      are no operative candidates. Operative treatment of choice is the posterior
      capsular shift addressing the causative redundancy or laxity of the postero
      inferior capsule. Posterior bony procedures as glenoid osteotomy or bone block
      transfers are indicated, if the pathologic geometry of the glenoid is primarily
      responsible for posterior instability. It is strongly recommended to combine them
      with a capsular shift to address the secondary capsular redundancy.

PMID- 9779431
TI  - [Management of old neglected posttraumatic acromioclavicular joint instability
      and arthrosis].
AB  - Resection arthroplasty of the AC joint was performed in 42 cases of
      osteoarthrosis and residual instability of traumatic origin including 26
      shoulders with horizontal instability of more than half of the width of the
      clavicula and lesions of the deltotrapezoid fascial complex (Rockwood type II: 7;
      type III: 9; type IV: 17; type V: 9). 23 cases were treated with a sole Weaver
      Dunn procedure. 26 cases with horizontal instability and lesions of the
      deltotrapezoid fascia (Rockwood IV and V type) were treated in 7 cases with the
      standard Weaver-Dunn procedure and in 19 cases with a modified Weaver-Dunn
      procedure in combination with a coracoclavicular (3 x 1) and acromio-clavicular
      (1 x 1) 1 mm PDS string augmentation and double breasting fascioplasty of the
      deltotrapezoid complex. RESULTS: Successful results (in Patte-Score) after a
      minimum follow-up of 2 years (mean: 32 months) were reached in 88.4% of cases
      with only Weaver/Dunn procedure with a significant difference of good and
      excellent results in the horizontally stable group (93.8%) versus the
      horizontally unstable group (57.2%). In the group with horizontal instability and
      Weaver-Dunn procedure and complex additional stabilization with fascioplasty and
      PDS augmentation, 89.5% excellent and good results were found. CONCLUSION: Cases
      with horizontal instability (type Rockwood IV and V) seem to be over-represented
      among patients with failed conservative treatment. Resection arthroplasty with
      ligament transposition after Weaver/Dunn gives excellent results in posttraumatic
      osteoarthrosis with mainly vertical and moderate horizontal instability. In cases
      with advanced horizontal instability after Rockwood IV and V injuries, almost
      equal results can be reached by an additional coracoclavicular and
      acriomioclavicular PDS augmentation with deltotapezoid fascioplasty.

PMID- 9779432
TI  - [Instability of the sternoclavicular joint].
AB  - Instability of the sternoclavicular joint is a rare diagnosis and will mostly be
      found after motor vehicle accidents or sports injuries. Depending on the severity
      of the trauma open reduction is rarely required, and most cases will be treated
      successfully with conservative management. Associated injuries to the surrounding
      anatomic structures are not rare, and can be found in posteriorly directed
      injuries.

PMID- 9779434
TI  - [Basic therapeutics in the management of various forms of arthritis].

PMID- 9779433
TI  - [Shoulder joint instability after primary arthroplasty].
AB  - Instability is one of the most common complications after shoulder arthroplasty.
      The literature cites subluxation or luxation to occur between 0% and 38% in
      various studies. Instabilities may present either as subluxation or frank
      dislocation, and may be directed in an anterior, posterior, inferior or,
      depending on the state of the rotator cuff, cranial direction. The stability of
      any shoulder joint is given by the balance of the muscles directing the forces
      around the shoulder joint in association with the passive stabilizers of the
      shoulder joint capsule as well as the bony contours between glenoid and humeral
      head. Any disturbance of this delicate balance will lead the shoulder into
      instability, particular so if bony erosion patterns such as posterior glenoid
      wear in osteoarthritics will develop subluxation early on. Therefore implantation
      of any prosthesis is required to be done in the appropriate version as to avoid
      secondary instability through the prosthetic components. In the study undertaken
      here instability was found to be the most common complication in 44 shoulder
      revision surgeries. The result with an average Score of 41.9 recorded after
      Constant demonstrates that the excellent and good results obtained with primary
      arthroplasties can not be expected in revision surgery. Posterior instability may
      be present just as well as the more easily observed anterior instability.
      Separate to frank luxation or instability is the late cranialisation of the
      rotator cuff deficient shoulder which, although resulting in many cases in
      superior anterior subluxation, will mostly be seen as a late complication after
      arthroplasty.

PMID- 9779435
TI  - [Hormone substitution in postmenopause (ERT and HRT) Current trends].

PMID- 9779436
TI  - [Carpal tunnel syndrome].

PMID- 9779437
TI  - Purification, hydrodynamic properties, and glycosylation analysis of glycine
      transporters.

PMID- 9779439
TI  - Cloning of genes or cDNAs encoding neurotransmitter transporters and their
      localization by immunocytochemistry.

PMID- 9779438
TI  - Expression cloning using Xenopus laevis oocytes.

PMID- 9779440
TI  - Purification of vesicular monoamine transporters: from classical techniques to
      histidine tags.

PMID- 9779441
TI  - Noncovalent and covalent labeling of vesicular monoamine transporter with
      tetrabenazine and ketanserin derivatives; purification of photolabeled protein.

PMID- 9779442
TI  - Functional identification of vesicular monoamine and acetylcholine transporters.

PMID- 9779443
TI  - Photoaffinity labeling of vesicular acetylcholine transporter from electric organ
      of Torpedo.

PMID- 9779444
TI  - Bioenergetic characterization of gamma-aminobutyric acid transporter of synaptic
      vesicles.

PMID- 9779446
TI  - Analysis of neurotransmitter transport into secretory vesicles.

PMID- 9779445
TI  - Solubilization and reconstitution of synaptic vesicle glutamate transport system.

PMID- 9779447
TI  - Inhibitors of gamma-aminobutyric acid transport as experimental tools and
      therapeutic agents.

PMID- 9779448
TI  - Design and synthesis of conformationally constrained inhibitors of high-affinity,
      sodium-dependent glutamate transporters.

PMID- 9779449
TI  - Examination of glutamate transporter heterogeneity using synaptosomal
      preparations.

PMID- 9779450
TI  - Specificity and ion dependence of binding of GBR analogs.

PMID- 9779451
TI  - Cocaine and GBR photoaffinity labels as probes of dopamine transporter structure.
AB  - Several aspects of DAT structure and function have been elucidated using a
      combination of photoaffinity labeling, proteolysis, enzymatic deglycosylation,
      and epitope-specific immunoprecipitation. The two photolabels are incorporated in
      different regions of the protein, suggesting that the binding sites for the
      ligands are distinct or partially nonoverlapping, consistent with results
      produced by site-directed mutagenesis and analysis of chimeras. These studies
      have also verified several aspects of DAT structure previously hypothesized based
      only on theoretical considerations, including the presence of at least one
      transmembrane helix or other membrane-anchoring structure in two different
      regions of the protein, identification of the glycosylated domain, and some
      topological properties. It should be possible to extend and adapt these
      techniques to further delineate DAT structural properties and to identify other
      functional domains such as phosphorylation sites or active sulfhydryl moieties.

PMID- 9779452
TI  - Ion-coupled neurotransmitter transport: thermodynamic vs. kinetic determinations
      of stoichiometry.

PMID- 9779454
TI  - Transport and drug binding kinetics in membrane vesicle preparation.

PMID- 9779453
TI  - Inhibition of [3H]dopamine translocation and [3H]cocaine analog binding: a
      potential screening device for cocaine antagonists.

PMID- 9779455
TI  - Use of human placenta in studies of monoamine transporters.

PMID- 9779457
TI  - Selective labeling of neurotransmitter transporters at the cell surface.

PMID- 9779456
TI  - Analysis of transporter topology using deletion and epitope tagging.

PMID- 9779458
TI  - Transmembrane topology mapping using biotin-containing sulfhydryl reagents.

PMID- 9779459
TI  - Probing structure of neurotransmitter transporters by substituted-cysteine
      accessibility method.

PMID- 9779460
TI  - Biosynthesis, N-glycosylation, and surface trafficking of biogenic amine
      transporter proteins.

PMID- 9779461
TI  - Expression of neurotransmitter transport systems in polarized cells.

PMID- 9779462
TI  - Localization of transporters using transporter-specific antibodies.

PMID- 9779463
TI  - Generation of transporter-specific antibodies.

PMID- 9779464
TI  - Homologies and family relationships among Na+/Cl- neurotransmitter transporters.

PMID- 9779465
TI  - Vaccinia virus-T7 RNA polymerase expression system for neurotransmitter
      transporters.

PMID- 9779466
TI  - Baculovirus-mediated expression of neurotransmitter transporters.

PMID- 9779467
TI  - Dopamine transporter mutants, small molecules, and approaches to cocaine
      antagonist/dopamine transporter disinhibitor development.

PMID- 9779468
TI  - In vivo generation of chimeras.

PMID- 9779469
TI  - Structural determinants of neurotransmitter transport using cross-species
      chimeras: studies on serotonin transporter.

PMID- 9779470
TI  - Molecular cloning of neurotransmitter transporter genes: beyond coding region of
      cDNA.

PMID- 9779471
TI  - Use of antisense oligodeoxynucleotides to inhibit expression of glutamate
      transporter subtypes.
AB  - Antisense ODN are highly effective tools to selectively inhibit synthesis of
      glutamate transporter subtypes. They have been used to evaluate the biology of
      individual transporter subtypes in vivo and in vitro. Appropriate use of
      antisense ODN, however, requires a number of important controls to validate the
      specificity of their effects. Ultimately, the efficacy at inhibiting the
      synthesis of transporters proteins reflects several variables: the actual
      efficacy of the antisense to directly inhibit synthesis, the rate of degradation
      of the ODN, the rate of intracellular penetration of the ODN, the rate of new
      protein synthesis for the transporter subtype, and the actual penetration of the
      ODN into CNS tissue. The methods described in this chapter will help one to
      optimize each of these parameters.

PMID- 9779472
TI  - Using Caenorhabditis elegans to study vesicular transport.

PMID- 9779473
TI  - Measurement of transient currents from neurotransmitter transporters expressed in
      Xenopus oocytes.
AB  - Electrophysiological measurements add new dimensions to the study of
      neurotransmitter transporters. (1) One can perform measurements with high
      temporal resolution (however, uptake of radioactive substrate is limited in that
      it cannot resolve events that occur within 1 sec, which is greater than the time
      of a single transport cycle). (2) Electrophysiology provides information about
      partial steps in transport cycles, including the fact that ion binding and
      dissociation at transporters can generate currents, which provides new insights
      about ion-transporter interaction. (3) Electrophysiology provides information
      about single transporter molecules, from patch-clamp recordings of single-channel
      activity of neurotransmitter transporters. At present, little is known about the
      molecular mechanisms that underlie transport. Electrophysiological measurements
      of ion binding and permeation contribute to the analysis of mutations that affect
      transport. Electrophysiology may help to identify amino acids and domains in
      neurotransmitter transporters that participate in specific ways in the transport
      process, such as ion neurotransmitter binding, permeation pathways, voltage
      sensors, and gates. In combination with spectroscopic measurements, it may also
      be possible to identify the actual conformational changes of the proteins that
      enable substrate translocation.

PMID- 9779474
TI  - Fluorescence techniques for studying cloned channels and transporters expressed
      in Xenopus oocytes.

PMID- 9779475
TI  - Fluctuation analysis of norepinephrine and serotonin transporter currents.
AB  - Findings from an electrophysiological analysis of neurotransmitter transporters
      show that transmitter-induced currents are associated with these transporters:
      For charged transmitters, such as NE and 5-HT, a fraction of the total current is
      carried by the transmitter itself; however, the transmitter also induces an extra
      current in analogy to an ligand-gated ion channel. An additional conductance not
      discussed in this article is the so-called leak, in which neurotransmitter
      transporters generate an ionic current in the absence of transmitter. Using a
      combination of flux measurements, voltage clamp, and fluctuation analysis has
      shown that, for norepinephrine and serotonin transporters, the transmitter
      induced current greatly exceeds the transmitter current. Such data can provide an
      exact measure of the ratio of these charge movements to transmitter translocation
      at the molecular level, suggesting new strategies to understand neurotransmitter
      transporters.

PMID- 9779476
TI  - Serotonin transport in cultured leech neurons.

PMID- 9779477
TI  - Glutamate uptake in Purkinje cells in rat cerebellar slices.
AB  - We have described how whole-cell clamping of neurons in brain slices has allowed
      a characterization of postsynaptic transporters, probably a mixture of EAAC1 and
      EAAT4, in cerebellar Purkinje cells. Similar experiments have been carried out on
      transporters (mainly GLAST) in cerebellar Bergmann glia, and have revealed an
      uptake current occurring as these carriers remove glutamate released at the
      parallel fiber synapses. As more transporters are cloned and their regulation is
      characterized in heterologous expression systems, it will be increasingly
      important to use methods similar to those outlined above to investigate to what
      extent the behavior of the carriers is similar in situ in the nervous system.

PMID- 9779478
TI  - Patch-clamp, ion-sensing, and glutamate-sensing techniques to study glutamate
      transport in isolated retinal glial cells.
AB  - We have described how a combination of electrical, ion-sensing, and glutamate
      sensing techniques has advanced our understanding of glutamate uptake into
      isolated salamander retinal glial cells. The next steps in understanding
      glutamate transport will inevitably depend strongly on molecular biological
      methods, as described elsewhere in this book, but will also require more detailed
      study of transporters in their normal environment, perhaps by using patch
      clamping or imaging techniques to study cells in situ.

PMID- 9779479
TI  - Measurement of glial transport currents in microcultures: application to
      excitatory neurotransmission.

PMID- 9779480
TI  - Voltammetric studies on kinetics of uptake and efflux at catecholamine
      transporters.

PMID- 9779482
TI  - Electrochemical detection of reverse transport from Planorbis giant dopamine
      neuron.

PMID- 9779481
TI  - Resolution of biogenic amine transporter kinetics by rotating disk electrode
      voltammetry: methodology and mechanistic interpretations.

PMID- 9779483
TI  - Measuring uptake rates in intact tissue.

PMID- 9779484
TI  - High-speed chronoamperometric electrochemical measurements of dopamine clearance.

PMID- 9779486
TI  - Inflammatory myxoid tumor of the soft parts with bizarre giant cells.
AB  - We present five cases of a tumor which we named inflammatory myxoid tumor of the
      soft parts with bizarre giant cells and which is often misdiagnosed as a
      malignant neoplasm. The tumors were located in the soft tissues of the fingers
      and hand and were 1 to 2.5 cm in the largest diameter (median 2 cm). The tumors
      were divided by fibrous septa into lobules. The lobules were composed of numerous
      proliferating capillaries and tumor cells, both set in copious myxoid
      extracellular matrix. Variously dense inflammatory infiltrate represented by
      numerous lymphocytes and plasma cells and sparse neutrophil leukocytes surrounded
      the capillaries. The tumor cells had one, two, or more nuclei. The nuclei of the
      tumor cells were vesicular, often indented or cleaved and they usually had one
      small nucleolus. The cytoplasm displayed characteristic clear vacuoles filled
      with mucous substances. In some of the tumor cells the cytoplasmic vacuoles
      filled the whole cytoplasm and compressed or indented the nucleus. Such cells had
      an appearance of signet ring cells. The cytoplasm of some of the cells often
      contained lymphocytes and leukocytes. All four patients with follow-up were
      without signs of recurrence and metastasis 2, 4, 6 and 7 years after the
      diagnosis.

PMID- 9779485
TI  - In vivo microdialysis for measurement of extracellular monoamine levels following
      inhibition of monoamine transporters.

PMID- 9779487
TI  - Pseudoangiomatous hyperplasia of the mammary stroma: true entity or phenotype?
AB  - We report the clinical and pathologic features seen in 14 cases of
      pseudoangiomatous hyperplasia of the mammary stroma. The lesion manifested as a
      discrete palpable lump in twelve women and two men. The excisional biopsy
      specimens showed firm, circumscribed grey-tan lesions measuring from 3 to 5.5 cm
      in largest dimension. Histologic study revealed diffuse, anastomosing, enlongated
      slits with open lumina, covered by spindle cells with bland nuclei and no mitotic
      activity. Strong reactivity for vimentin and CD34 was noted. Smooth muscle actin
      was focally noted in most cases. Immunostains for other markers, including CD31
      and factor VIII related antigen was negative. Spindle cells from two cases
      expressed both estrogen and progesterone receptors. In all the cases, there was
      some degree of glandular hyperplasia accompanying the stromal changes.
      Fibroadenoma or fibrocystic disease were also common features. Our study confirms
      that pseudoangiomatous hyperplasia of mammary stroma represents a proliferation
      of local myofibroblasts, likely related to a hormonal stimulus. The wide range of
      associated changes of breast parenchyma further indicates that this lesion may
      represent a local, non specific change rather than a true clinico-pathologic
      entity.

PMID- 9779488
TI  - Correlated expression of BCL-2 protein, estrogen receptor, cathepsin D and low
      growth fraction (PCNA) in intracystic papillary breast carcinoma.
AB  - The expression of BCL-2 protein was evaluated immunohistochemically in 23
      intracystic papillary carcinomas (IPCs) of the breast. Twenty-two patients were
      female and one male, aged 49-90 years (median 72). Twenty-one cases had a benign
      behaviour, while two cases developed local recurrence. Of the 23 tumours, 19
      (82%) were immunoreactive for BCL-2, the majority of positive carcinomas showing
      intense cytoplasmic staining of more than 50% neoplastic cells. The intensity of
      BCL-2 expression was significantly correlated with prognostic markers such as
      estrogen receptor (ER) positivity (p = 0.001), cathepsin D (CD) reactivity in the
      neoplastic cells (p = 0.001) and low growth fraction, evaluated by proliferating
      cell nuclear antigen (PCNA) immunostaining (p = 0.008). An inverse relationship
      was also found between BCL-2 and p53 protein (p = 0.001). Three cases of high
      grade (G3) IPC expressed p53, high PCNA index, and CD (the latter only in the
      stromal cells), but no immunostaining for BCL-2 and ER. Thus, absence of BCL-2
      expression in high grade IPC was associated with ER-negative, rapidly
      proliferating and p53-positive immunophenotype. All high grade tumours showed
      invasion of the cystic wall. Local recurrence developed in one of these. The
      authors conclude that BCL-2 immunoreactivity in IPC is related with tumour grade
      and with a range of molecular markers of favourable prognosis such as ER positive
      status, CD expression in the neoplastic cells, and low PCNA index. These findings
      are consistent with the indolent clinical course and the very favourable
      prognosis of IPC of the breast.

PMID- 9779489
TI  - Spontaneous programmed cell death in infiltrating duct carcinoma: association
      with p53, BCL-2, hormone receptors and tumor proliferation.
AB  - Recent evidence has emphasized the importance of programmed cell death or
      apoptosis in the maintenance of tissue homeostasis and pathogenesis of tumors.
      This study, analyzed in breast cancer, investigates the significance of apoptosis
      in relation to the expression of p53 and bcl-2 proteins, tissue proliferation
      defined by Ki-67 expression, hormone receptors and tumor grade. The extent of
      apoptosis was defined by morphological criteria and the TUNEL (Tdt-mediated dUTP
      biotin nick end labelling) assay. Immunocytochemistry was performed for p53, bcl
      2, estrogen receptor, progesterone receptor and Ki-67 expression. Mutant p53
      protein was detected using a mutant specific ELISA. Immunoreactivity of p53
      significantly correlated with the presence of mutant p53 protein detected by
      ELISA (r = 0.654, p = 0.00001). An inverse correlation was observed between bcl-2
      expression and the extent of apoptosis (r = -0.33369, p = 0.01912). The extent of
      apoptosis directly correlated with p53 protein accumulation (r = 0.485, p =
      0.00041), Ki-67 immunoreactivity (r = 0.435, p = 0.001), histopathological grade
      (r = 0.492, p = 0.0003), tumor size (r = 0.326, p = 0.023) and lymph node status
      (r = 0.287, p = 0.047). A direct correlation was also observed between p53
      expression and Ki-67 immunoreactivity (r = 0.623, p = 0.0002). There was no
      statistically significant association between estrogen and progesterone receptor
      status and apoptosis. In addition, the TNM stage of the disease correlated with
      immunoreactivity of p53 (r = 0.572, p = 0.00012) and Ki-67 (r = 0.3744, p =
      0.00818). Bcl-2, by inhibiting apoptosis, may cause a shift in tissue kinetics
      towards the preservation of genetically aberrant cells, thereby facilitating
      tumor progression. These results imply that rapidly proliferating tumors appear
      to have a high "cell turnover state" in which there may be an increased chance of
      apoptosis amongst the proliferating cells. The ability of apoptosis to also occur
      in the presence of mutant p53 protein suggests the existence of at least two p53
      dependent apoptotic pathways, one requiring activation of specific target genes
      and the other independent of it.

PMID- 9779490
TI  - Occurrence of monocytoid B-cells in reactive lymph node lesions.
AB  - Benign monocytoid B-cells are a peculiar subset of B-cells. They are closely
      related to marginal zone B-lymphocytes, show cytological diversity and may be
      recognized in a variety of reactive lymph node conditions. To analyze the
      incidence, cytological spectrum and phenotypic features of benign monocytoid B
      cells, we investigated a series of 301 consecutively biopsied and unselected
      cases of reactive lymph node change from 1988 and 1995. A monocytoid B-cell
      reaction was identified in 46 (15%) cases and could be cytologically
      subclassified into two groups: 31 (67%) cases with common-type cells and 15 (33%)
      cases with large, transformed cells, according to the description by Plank et al.
      [19]. These reactions were regularly associated with follicular hyperplasia (95%)
      and were part of an epithelioid cell response in 24 cases (50%).
      Immunohistologically, both types of benign monocytoid B-cells were negative for
      bcl-2 protein expression, which was in contrast to the bcl-2 positive reaction in
      marginal zone B-lymphocytes and their neoplastic counterpart in monocytoid B-cell
      lymphoma. An association of Epstein-Barr virus (EBV) with monocytoid B-cells was
      investigated by in situ-hybridization. EBV genomes were detected in five (15%) of
      31 cases tested. In each of these five cases, positive cells were represented in
      both high and low numbers. The morphologic features of the EBV-positive cells
      were not consistent with monocytoid B-cells, but rather with medium-sized to
      large lymphoid cells. It appeared that the occurrence of monocytoid B-cell
      reaction in reactive lymph node lesions was not related to EBV infection in the
      majority of cases.

PMID- 9779491
TI  - AIDS-associated nephropathy: 5-year retrospective morphologic analysis of 87
      cases.
AB  - Morphologic findings in the kidneys of 138 consecutive acquired immunodeficiency
      syndrome (AIDS) autopsies performed at the Mexico City General Hospital between
      1986 and 1991 were studied. A total of 87 cases (63%) had renal disease, 62 cases
      presented glomerular alterations, and 80 cases showed tubulointerstitial damage.
      Glomerular collapse was seen in 30 cases (48%), mesangial expansion in 22 cases
      (35%), focal and segmental glomerulosclerosis in 20 cases (32%) and glomerular
      proliferation in only eight cases (11%). Nephrocalcinosis was seen in 25 cases
      (31%). Thirty-six cases (45%) presented tubulointerstitial infections:
      Mycobacterium tuberculosis in 19 cases (23%), Cryptococcus in 10 cases (12.5%),
      Cytomegalovirus CMV in eight cases (10%), Gram-negative bacteria in 3 cases
      (3.7%), and one case with histoplasmosis. In six cases the pathogens were
      multiple. Two cases showed infiltration of large-cell non-Hodgkin lymphoma. Based
      on the results obtained by autopsies, we conclude that in our country there is a
      high frequency of renal affection in AIDS patients. Clinically, this disease is
      infrequently diagnosed and not always related to the cause of death.

PMID- 9779492
TI  - The long-term prognosis of benign nephrosclerosis accompanied by focal
      glomerulosclerosis and renal cortical interstitial fibrosis, designated so-called
      decompensated benign nephrosclerosis by Fahr, Bohle and Ratscheck.
AB  - The long-term prognosis of decompensated benign nephrosclerosis (DBN) was
      investigated by a retrospective analysis of the fate of 170 patients with this
      disease, which yielded the following results: 1) DBN carries a particularly poor
      prognosis. The renal survival rate (RSR) was 35.9% at 5 years and 23.6% at 10
      years. The prognosis is therefore worse than that of any other primary
      glomerulopathy, with the exception of rapidly progressive glomerulonephritis. 2)
      DBN mainly affects males (sex ratio 5:1) and differs in this respect, among
      others, from focal sclerosing glomerulonephritis, in which the male:female ratio
      is 1.2:1. 3) The prognosis for females is no better than for males. 4) The
      severity of proteinuria at the time of biopsy has no influence on the prognosis.
      5) The prognosis is particularly poor in cases in which the serum creatinine
      concentration is already elevated to more than 2.0 mg% at the time of biopsy. We
      conclude from these findings that not only the blood pressure, but also the serum
      creatinine concentration, should be assessed at regular intervals in all
      hypertensive individuals, so that DBN can be treated at an early stage, when it
      is still amenable to treatment.

PMID- 9779493
TI  - Hyalinizing spindle cell tumors with giant rosette-like structures.
AB  - We report two cases of hyalinizing spindle cell tumors with giant rosettes
      arising in the pararectal space and soft tissues of the wrist in a 46-year-old
      man and 22-year-old-woman, respectively. Microscopically, the tumors exhibited a
      varied morphology, including hyalinizing hypocellular and cellular fibromatosis
      like areas. The most striking morphologic feature was the formation of giant
      rosette like structures with collagen cores scattered throughout the tumors. Most
      of the tumor spindle cells were diffusely immunoreactive for lysozyme, CD-68,
      factor XIII and vimentin. Reactivity for smooth muscle actin, desmin and S-100
      protein was not found. Ultrastructural examination of the rosettes in one case
      only showed normal native collagen.

PMID- 9779494
TI  - Osteoclast-like giant cell tumor of the pancreas with metastases to gallbladder
      and lymph nodes. A case report.
AB  - Osteoclast-like giant cell tumor of the pancreas (OGTP) is a rare neoplasm, of
      which the histogenesis is still controversial. Here we report a case of OGTP
      involving the head of the pancreas in a 71-year-old woman with metastases to the
      gallbladder and lymph nodes. The primary and metastatic tumors had identical
      histopathological, immunohistochemical, ultrastructural and molecular biological
      features. Microscopically, the tumors were characterized by atypical, often
      pleomorphic mononuclear cells associated with the proliferation of benign
      appearing osteoclast-like giant cells (OGCs). Electron microscopic observation
      provided ultrastructural evidence of epithelial differentiation of the
      mononuclear cells, including microvilli and desmosomes, which was not obtained
      for OGCs. On immunohistochemical study, OGCs stained for CD68 (KP-1), LCA and
      HAM56, whereas mononuclear cells only reacted with PCNA. These findings clearly
      suggest that mononuclear cells are capable of differentiation and proliferation
      and may have been the only true tumor cells in this neoplasm, and that OGCs may
      have been a paraneoplastic product of this rare tumor. On examination of DNA from
      dewaxed sections of the tumor, we found no p53 mutation in the tumor tissue, but
      found two K-ras mutations in codon 12; this pattern of mutation commonly occurs
      in pancreatic carcinoma, indicating a somewhat genetic relationship of OGTP to
      pancreatic carcinoma. Although OGTP often has a favorable prognosis, the outcome
      in the present case was poor due to early tumor spread, with less than two years
      postoperative survival.

PMID- 9779495
TI  - Commercial sunscreen lotions prevent ultraviolet radiation-induced depletion of
      epidermal Langerhans cells in Skh-1 and C3H mice.
AB  - There is much controversy regarding the ability of sunscreens to prevent
      ultraviolet (UV)-induced immune suppression. Epidermal Langerhans cells (LC) play
      a key antigen-presenting role in the afferent limb of the immune system's
      response to antigens introduced through the skin. It has been suggested that
      depletion of LC in UV-exposed skin is a critical step toward the induction of
      immunosuppression by UV radiation. There are a number of disparate reports with
      inconsistent results concerning the ability of sunscreens to prevent UV-induced
      depletion of LC. The purpose of this study was to systematically evaluate the
      ability of sunscreens to prevent UV-induced LC depletion in mice. Epidermal
      sheets obtained from skin biopsies taken from mice exposed to UV radiation from
      Kodacel-filtered FS20 sunlamps, which do not emit UV power at wavelengths < 290
      nm, were immunoperoxidase stained for LC using a rat monoclonal antibody against
      mouse Ia (major histocompatibility complex class II antigen). Time course and
      dose-response curves for LC depletion were generated for Skh-1 and C3H mice. Dose
      response curves for acute UV exposure induced depletion of LC in Skh-1 and C3H
      mice were similar, but not identical. LC density in the skin of Skh-1 mice that
      received chronic UV exposure (3 days/week for 8 weeks) was reduced by 62% after 2
      weeks of exposure, but returned to normal levels by 6 weeks. Five commercial
      sunscreen lotions with labeled sun protection factors (SPF) of 4, 8, 15, 30 and
      45 were tested for their capacity to block UV-induced depletion of LC. LC were
      depleted approximately 75% in the skin of unprotected or placebo lotion treated
      Skh-1 mice exposed to UV given on two consecutive days. Conversely, LC depletion
      was prevented in similarly UV exposed Skh-1 mice protected with a SPF 30
      sunscreen. In C3H mice the levels of protection against LC depletion provided by
      the five sunscreens were proportional to the level of protection predicted by
      their labeled SPF. Comparisons of dose-response curves showed that significantly
      higher doses of UV were required for LC depletion and induction of skin edema
      than for the induction of local suppression of contact hypersensitivity. Thus, at
      UV doses where sunscreens provide complete protection against immunosuppression
      of contact hypersensitivity, prevention of LC depletion and skin edema would be
      expected.

PMID- 9779496
TI  - Measurement of cutaneous erythema by means of photodensitometry: application to
      cutaneous photosensitivity.
AB  - We have developed a photodensitometry method to evaluate the intensity of
      cutaneous erythema objectively. The method measures the optical density of
      photographic slides of cutaneous erythema. It combines techniques used commonly
      but separately by investigators: diffuse transmittance spectroscopy (which is a
      variant of diffuse reflectance spectroscopy) and photography. We have used this
      method to study photosensitivity in 22 volunteers who received increasing doses
      of ultraviolet radiation to the back. Our work confirms the usefulness of an
      important parameter in photobiology: the regression slope of the curve
      representing the erythema index, a function of the logarithm of the dose applied.

PMID- 9779497
TI  - Changes of minimal erythema dose after water and salt water baths.
AB  - Knowledge about the influence of salt water baths on UV irradiation, especially
      balneophototherapy, is incomplete. The aim of this study was to investigate the
      influence of various concentrated salt solutions on the minimal erythema dose
      (MED). We determined the MEDdry (UVB) in 24 healthy, previously UV unexposed
      subjects on the inner forearm. Subjects were divided randomly into two groups of
      12. Subsequently, the MEDwet was assessed on each forearm after 30 min tap water
      or 5% salt water bath (group A), respectively, or after 30 min 10% or 20% salt
      water bath (group B), respectively. Compared with the MEDdry, a significantly
      decreased MEDwet, was observed after all exposures (group A==>F = 18.94; P <
      0.001; group B==>F = 11.73; P < 0.006). A maximal relative decrease in MEDdry of
      about 51.4% was observed after the 10% salt water bath. The 5% salt solution
      caused a modest relative decrease in MEDwet of 23.4%. We observed a markedly
      increased photosensitivity to UVB after all exposures, without a linear
      correlation between the MED and the salt water concentration. A determination of
      MED during balneophototherapy should be carried out after bathing in order to
      reduce the cumulative UV dose and to prevent acute photodamage.

PMID- 9779498
TI  - A comparison of erythema efficacy of ultraviolet B irradiation from Philips TL12
      and TL01 lamps.
AB  - The erythema efficacy of UVB irradiation from Philips TL12 and TL01 lamps has
      been evaluated and compared. Thirty-seven healthy Thai volunteers were irradiated
      on the previously unexposed lower back with TL12 and TL01 lamps in doses ranging
      100 to 550 mJ/cm2 and 360 to 2020 mJ/cm2, respectively. Erythema was evaluated
      clinically and measured by a narrow-band spectrophotometer before exposure and 24
      h after exposure. The threshold doses of UVB that induced barely perceptible
      erythema (MEDb) with well-defined border erythema (MEDw) and the steepness of the
      dose-response curves for erythema (DRAE) were compared. We found that MEDb and
      MEDw of the TL01 lamps were 4.19 and 4.52 times those of TL12 lamps, which were
      similar to those calculated from the CIE erythema action spectrum (4.2). However,
      the DRAE of the two lamps were quite similar. Because the initial dosage of UVB
      phototherapy is usually given as a percentage of a patient's MED, the initial
      exposure of TL01-UVB phototherapy should be about 4.2 times that of TL12-UVB.

PMID- 9779499
TI  - Influence of dietary lipid on hapten-specific UV-induced immunosuppression.
AB  - The influence of diets containing high (12%, w/w) and low (0.75%) levels of corn
      oil on hapten-specific antibody production to trinitrophenol-conjugated sheep red
      blood cells (TNP-SRBC) was examined in mice receiving 0, 3, 9, and 11 wk of UV
      radiation. Splenocytes from HRA HRII-c/+/Skh female hairless mice from the two
      dietary groups were incubated under a special atmosphere of low oxygen tension
      (7% O2, 10% CO2, and 83% N2) with TNP-SRBC to generate hapten-specific T
      suppressor cells that, in turn, influence the number of direct plaque forming
      cells (PFC) in the Cunnigham-Szenberg plaque assay. Chronic UV irradiation
      reduced the number of direct PFC in both groups. After 11 wk of UV, the number of
      PFC in the high dietary fat group was significantly lower (P < 0.001) than that
      observed in the low fat group. These results suggest that dietary fat modulates
      UV-induced hapten-specific immunosuppression. Furthermore, the influence of
      dietary fat level, in this respect, was not realized until after 11 wk of UV, a
      time at which dietary fat has been shown to exert its influence on UV
      carcinogenic expression.

PMID- 9779500
TI  - Effects of PUVA and UVB treatments on restoration of epidermal barrier function
      and vascular response after suction blister injury in human skin in vivo.
AB  - PUVA and UVB phototherapies are used in the treatment of psoriasis and other
      inflammatory skin diseases. Ultraviolet radiation causes inflammation and
      modulates cell kinetics in the skin. PUVA also has an inhibitory effect on skin
      DNA synthesis. In this study, the effects of PUVA and UVB treatments on epidermal
      would healing were examined using the suction blister wound model. The healing of
      the wound was studied indirectly by measuring water evaporation and blood flow in
      the wound area. On the fourth day, water evaporation was more abundant in PUVA
      treated patients (42 +/- 5 g/m2h) than in UVB treated (36 +/- 4 g/m2h) or control
      patients (27 +/- 3 g/m2h) (analysis of variance, the least significant difference
      test at a level of 0.05). The P value for the difference of means between the
      PUVA and control groups was 0.014. Blood flow was also more abundant during the
      fourth (PUVA 162 +/- 11 arbitrary units, UVB 122 +/- 10, controls 115 +/- 15) and
      sixth (PUVA 108 +/- 18, UVB 73 +/- 17, controls 57 +/- 13) day in PUVA treated
      patients (analysis of variance, the least significant difference test at a level
      of 0.05). The results suggest that PUVA treatment decreases the restoration of
      the epidermal barrier function. The PUVA-treated patients also showed a more
      intense and prolonged vascular response that may be due to PUVA-related
      inflammation.

PMID- 9779501
TI  - Photosensitization of skin-derived cell lines by Dimegin [2,4-di-(alpha
      methoxyethyl)-deuteroporphyrin IX] in vitro.
AB  - The deuteroporphyrin-IX derivative Dimegin [2,4-di-(alpha-methoxyethyl)
      deuteroporphyrin IX] was investigated with respect to cellular uptake,
      intracellular localization and cell survival following photodynamic treatment in
      human cell lines derived from the skin (SCL1 and SCL2, squamous cell carcinoma;
      HaCaT keratinocytes; N1 fibroblasts). Using flow cytometry, we determined the
      cellular fluorescence as a marker of the uptake of Dimegin after incubation for
      24 h. The intracellular localization of Dimegin was analysed using fluorescence
      microscopy and co-staining with fluorescent dyes specific for cell organelles.
      Following irradiation with an incoherent light source (580-740 nm) using a light
      dose of 24 J/cm2, phototoxicity was determined by means of trypan blue dye
      exclusion, MTT assays and growth curves. The relative Dimegin fluorescence of the
      different cell lines declined as follows: SCL1 > HaCaT > N1 > SCL2. Intracellular
      localization of Dimegin was found in the mitochondria. For all cell lines Dimegin
      concentrations above 15 microM yielded a significant phototoxic effect. The EC50
      for SCL1 cells was 8.9 +/- 2.0 microM Dimegin. The EC50 for the cell lines
      increased as follows: SCL1 < HaCaT < N1 < SCL2, thus correlating with the
      cellular fluorescence of Dimegin. The results of the MTT assay were confirmed by
      trypan blue dye exclusion assay and growth curves. In conclusion, the study shows
      that Dimegin is an effective photosensitizer with a rapid mechanism of action in
      vitro, resulting in an immediate loss of plasma membrane integrity following
      irradiation.

PMID- 9779502
TI  - Rilmenidine-induced photosensitivity reaction.

PMID- 9779503
TI  - How effective are UV opaque face shields in UVB phototherapy cabins?
AB  - A few hours after servicing illuminated lamps inside a whole body ultraviolet
      radiation B (UVB) phototherapy cabin, a technician developed erythema to the
      anterior neck with subsequent peeling, despite wearing a UV-opaque face shield.
      Measurements using polysulphone film badges attached to various sites on the head
      and neck of a mannikin were carried out to explore the spatial distribution of
      UVB exposure. It was found that the lower face and neck can receive sufficient
      exposure to result in erythema, the reason being that the fluorescent lamps will
      extend to about 1.5 m inferior to the head of an upright person and so result in
      irradiation from below. It is important, therefore, that if operators or service
      personnel need to be in an illuminated UVB cabin for several minutes or more,
      adequate protection should be provided to the chin and neck, in addition to a UV
      opaque face shield.

PMID- 9779505
TI  - Solutions for a water-short world.

PMID- 9779504
TI  - Plasma levels of 8-methoxypsoralen following PUVA-bath photochemotherapy.
AB  - Administration of 8-methoxypsoralen (8-MOP) in a dilute bath water solution is an
      effective therapeutic alternative to oral PUVA therapy, avoiding systemic side
      effects, offering better bioavailability of the psoralen and requiring much
      smaller amounts of UVA for induction of therapeutic effects. To obtain exact data
      about the percutaneous absorption of 8-MOP during a psoralen bath, the plasma
      levels of the drug were determined in 26 patients with different skin diseases by
      a reverse high-performance liquid chromatographic method. Fifteen patients
      receiving oral PUVA therapy (0.8 mg 8-MOP/kg body weight) served as a positive
      control group. Bath solutions were prepared by diluting 15 ml of 0.5% stock
      solution of 8-MOP in 150 l of bath water (0.5 mg/l, 37 degrees C). Blood samples
      were drawn from patients 5, 30, 60, 120 and 180 min after the bath. In the oral
      PUVA group, blood samples were obtained 1 1/2 h after administration of the drug.
      In 23 of 26 patients, 8-MOP levels were undetectable in every blood sample. After
      30 min, two patients showed detectable levels of 8-MOP (5 ng/ml, 7 ng/ml), while
      60 min after the PUVA bath 8-MOP was detectable in only one volunteer (5 ng/ml).
      In patients receiving oral 8-MOP therapy, serum levels varied between 45 and 360
      ng/ml 1 1/2 h after drug administration. Our data confirm extremely low 8-MOP
      levels resulting from 8-MOP bath water treatments and provide confirmation of the
      absence of systemic side effects in patients who are undergoing PUVA-bath
      therapy.

PMID- 9779506
TI  - MR spectroscopy of Alzheimer disease.
AB  - Spectroscopy is a technique that permits noninvasive evaluation of biological
      metabolites. Used with magnetic resonance imaging, spectroscopy can measure
      metabolites associated with Alzheimer disease. Researchers are trying to find a
      distinct connection between the disease and certain metabolites so that an
      accurate diagnosis can be made during a patient's life. Speculation arises as
      chemical metabolites present in patients with Alzheimer disease also correlate
      with other dementia diseases. At present, in vitro and in vivo spectroscopy
      studies are assessing a baseline for an accurate diagnosis.

PMID- 9779507
TI  - Predictors of success on the ARRT's MRI exam.
AB  - The research described in this article investigated the relationship between
      selected background variables and the performance of 2546 candidates who took a
      certification examination in magnetic resonance imaging in 1995. Five variables
      related to training and experience were investigated: type of training in MR,
      amount of training in MR, years of experience in MR, hours per week in MR and
      number of MR scans performed per week. In addition, scores from an entry-level
      certification exam in general radiography were studied. Results indicated that
      all six variables were significantly related to MRI exam scores, with prior
      performance on the radiography exam exhibiting the strongest relationship.
      Implications of the findings for policy and practice are discussed.

PMID- 9779508
TI  - Understanding chronic illness from the patient's perspective.
AB  - As deaths from infectious diseases have declined, more Americans are living
      longer and developing chronic illnesses. This article examines the physical and
      social-psychological demands illness places on such patients and the implications
      for health care. It also examines, through a review of pertinent literature, the
      traditional Western model that informs medical practice. The article suggests
      that technical treatment, coupled with awareness of a patient's illness
      experience, perspective and work in the medical setting, leads to approaches that
      are healing.

PMID- 9779509
TI  - Lymphedema following breast cancer treatment.
AB  - Many breast cancer patients experience swelling of the arm and hand following
      treatment, a condition known as lymphedema. This article discusses the causes of
      lymphedema, its signs and symptoms, imaging and measurement techniques used to
      evaluate lymphedema and current approaches to treatment. The importance of
      patient education and the need for more research on lymphedema also are
      emphasized.

PMID- 9779511
TI  - Wet-type macular degeneration.

PMID- 9779510
TI  - Quality control and artifacts in mammography.
AB  - Effective mammography requires rigorous quality control, mandated by the
      Mammography Quality Standards Act of 1992 (MQSA). This article reviews MQSA's
      requirements and the elements of the imaging chain that affect mammogram quality.
      Major classes and sources of artifacts also are presented.

PMID- 9779512
TI  - Minimizing occupational exposure.

PMID- 9779513
TI  - Maslow in the classroom and the clinic.

PMID- 9779514
TI  - Sudden arousals from slow-wave sleep and panic disorder.

PMID- 9779515
TI  - Interrelations between sleep and the somatotropic axis.
AB  - In the human as in other mammals, growth hormone (GH) is secreted as a series of
      pulses. In normal young adults, a major secretory episode occurs shortly after
      sleep onset, in temporal association with the first period of slow-wave (SW)
      sleep. In men, approximately 70% of the daily GH output occurs during early sleep
      throughout adulthood. In women, the contribution of sleep-dependent GH release to
      the daily output is lower and more variable. Studies involving shifts of the
      sleep-wake cycle have consistently shown that sleep-wake homeostasis is the
      primary determinant of the temporal organization of human GH release. Effects of
      circadian rhythmicity may occasionally be detected. During nocturnal sleep, the
      sleep-onset GH pulse is caused by a surge of hypothalamic GHRH release which
      coincides with a circadian-dependent period of relative somatostatin
      disinhibition. Extensive evidence indicates the existence of a consistent
      relationship between SW sleep and increased GH secretion and, conversely, between
      awakenings and decreased GH release. There is a linear relationship between
      amounts of SW sleep--whether measured by visual scoring or by delta activity--and
      amounts of concomitant GH secretion, although dissociations may occur, most
      likely because of variable levels of somatostatin inhibition. Pharmacological
      stimulation of SW sleep results in increased GH release, and compounds which
      increase SW sleep may therefore represent a novel class of GH secretagogues.
      During aging, SW sleep and GH secretion decrease with the same chronology,
      raising the possibility that the peripheral effects of the hyposomatotropism of
      the elderly may partially reflect age-related alterations in sleep-wake
      homeostasis. While the association between sleep and GH release has been well
      documented, there is also evidence indicating that components of the somatotropic
      axis are involved in regulating sleep. The studies are most consistent in
      indicating a role for GHRH in promoting NREM and/or SW sleep via central, rather
      than peripheral, mechanisms. A role for GH in sleep regulation is less well
      documented but seems to involve REM, rather than NREM, sleep. It has been
      proposed that the stimulation of GH release and the promotion of NREM sleep by
      GHRH are two separate processes which involve GHRH neurons located in two
      distinct areas of the hypothalamus. Somatostatinergic control of GH release
      appears to be weaker during sleep than during wake, suggesting that
      somatostatinergic tone is lower in the hypothalamic area(s) involved in sleep
      regulation and sleep-related GH release than in the area controlling daytime GH
      secretion. While the concept of a dual control of daytime and sleep-related GH
      secretion remains to be directly demonstrated, it allows for the reconciliation
      of a number of experimental observations.

PMID- 9779516
TI  - A CLOCK polymorphism associated with human diurnal preference.
AB  - A single nucleotide polymorphism located in the 3' flanking region of the human
      CLOCK gene was investigated as a predictor of diurnal preference in a population
      based random sample of 410 normal adults. Morningness-eveningness preferences
      were determined using the 19-item Home-Ostberg questionnaire. Subjects carrying
      one of the two CLOCK alleles, 3111C, had a significantly lower mean Horne-Ostberg
      score. The distribution of scores was clearly shifted toward eveningness for
      these subjects. The score difference was independent of age, sex and ethnic
      heritage, thus making population stratification effects unlikely to explain this
      difference. These subjects had a substantial 10- to 44-minute delay in preferred
      timing for activity or sleep episodes. We suggest that the identified
      polymorphism or another tightly linked polymorphism within the CLOCK gene or its
      regulatory elements may be responsible for the finding.

PMID- 9779517
TI  - Nocturnal enuresis in a nationwide twin cohort.
AB  - We studied the occurrence of nocturnal enuresis (bedwetting) after the age of 4
      years, using a questionnaire in a well-defined population, the Finnish Twin
      Cohort, which consists of 11,220 subjects aged 33-60 years, including 1298
      monozygotic and 2419 dizygotic twin pairs. Structural equation modeling
      techniques were used to estimate variance components to compare different genetic
      models. Females reported enuresis in childhood "often" in 3.4% (males in 4.0%)
      and "sometimes" in 5.7% (8.0%). As adults, females had experienced enuresis
      "weekly" in 0.3% (males in 0.2%) and "monthly" in 0.07% (0.1%). Those who had
      experienced enuresis in childhood had had "at least sometimes" enuresis as adults
      in 5.4% of males and in 5.5% of females. Among those who reported they never had
      experienced enuresis as adults, 70.8% of males and in 77.9% of females had never
      experienced enuresis in childhood. For enuresis in childhood, the probandwise
      concordance rate was 0.43 for monozygotic and 0.19 for dizygotic pairs, and in
      adults 0.25 and 0, respectively. The proportion of total phenotypic variance
      attributed to genetic influences (due to dominance) was 67% in males (95%
      confidence interval 57-76%) and 70% in females (61-78%) in childhood enuresis. In
      conclusion, nocturnal enuresis is common in childhood and rare in adulthood. Our
      results confirm the central role of genetic liability in enuresis.

PMID- 9779518
TI  - Effect of NMDA lesion of the medial preoptic neurons on sleep and other
      functions.
AB  - This study was undertaken to determine the effects of the destruction of the
      medial preoptic area (mPOA) neurons by N-methyl D-aspartic acid (NMDA), on sleep
      wakefulness (S-W), locomotor activity, body weight, rectal temperature, and food
      and water intake in rats. The NMDA lesion of the mPOA produced long-lasting
      insomnia with marked reduction in the deeper stages of sleep, including
      paradoxical sleep. The reduction in the duration of sleep episodes in the
      lesioned rats indicated their inability to maintain sleep. The insomnia resulting
      from a decreased sleep pressure did not alter the sleep-initiating ability.
      Though the day-night distribution of sleep remained largely unaffected, there was
      an increase in locomotor activity during the light period. There was no increase
      in food intake to compensate for the high energy expenditure resulting not only
      from hyperactivity but also from hyperthermia in the mPOA-lesioned rats. Thus,
      body weights of the rats were reduced even without any change in food and water
      intake. However, the changes in body temperature and locomotor activity after the
      mPOA neuronal loss may not have exerted a major influence on S-W, as the
      alterations in all these parameters had different time courses.

PMID- 9779519
TI  - Recovery of sleep after fetal preoptic transplantation in medial preoptic area
      lesioned rats.
AB  - Changes in sleep after fetal preoptic (POA) tissue transplantation were studied
      in rats which had been made insomniac by a medial preoptic area (mPOA) lesion.
      Two days after the N-methyl D-aspartic acid (NMDA) lesion of the mPOA, fetal POA
      tissues (obtained from 14- to 17-day-old fetuses) were transplanted into the
      lesioned mPOA. Insomnia was less marked in these animals, as compared to
      nontransplanted lesioned rats, even on the 4th day after transplantation. The
      quantum of sleep nearly attained the prelesion level by the 20th day. Body weight
      also showed recovery after transplantation. Rectal temperature, which was
      increased by the lesion of the mPOA, remained unaltered even after the
      transplantation. These results suggest that the recovery of sleep and rectal
      temperature may follow different time courses. Surviving transplanted neurons
      were seen at the site of lesion on postmortem examination. Humoral interaction
      between the host and the transplant may be responsible for the early recovery of
      sleep, though the establishment of neural connections between the host and
      transplant might have contributed to the later recovery. This is the first study
      to show the recovery of sleep function in insomniac animals after fetal preoptic
      tissue transplantation. However, the specificity of the POA fetal tissue, in
      comparison with other neural tissues to promote sleep recovery, remains to be
      established.

PMID- 9779520
TI  - The effects of REM sleep deprivation on the level of sleepiness/alertness.
AB  - STUDY OBJECTIVES: The purpose of this study was to evaluate the effects of acute
      REM deprivation on daytime sleepiness/alertness, as measured by the MSLT.
      PARTICIPANTS: Twenty-six healthy, normal volunteers (14 males and 12 females)
      participated in this study. Participating subjects were in good physical and
      psychological health and were asymptomatic as to sleep/wake complaints.
      INTERVENTIONS: Subjects spent 5 nights and 5 days in the laboratory. The first
      night and day were utilized for screening purposes. The remaining stay in the
      laboratory consisted of a baseline night and day, 2 deprivation nights and days,
      and a recovery night and day. Each night, a nocturnal polysomnogram was employed
      to monitor subjects' sleep. Each day, subjects underwent an MSLT to evaluate
      their sleepiness/alertness. Subjects were randomized into REM-deprivation (RD)
      and yoked-control (YC) groups. On deprivation nights, RD subjects were awakened
      each time they entered stage REM sleep, and the YC subjects were awakened
      concomitantly with the RD subjects, assuming they were not in stage REM sleep.
      RESULTS: The REM-deprived subjects did not demonstrate any changes in MSLT scores
      across experimental days. In contrast, the YC subjects documented significantly
      lower MSLT scores on deprivation days due to decreased total sleep time.
      CONCLUSION: The REM-deprivation procedure antagonized the effects of sleep loss
      on daytime sleepiness, resulting in increased alertness for RD subjects compared
      to YC subjects. The mechanism by which REM deprivation exerts its alerting
      effects is unknown and will require future research.

PMID- 9779521
TI  - Effect of pergolide on restless legs and leg movements in sleep in uremic
      patients.
AB  - Restless legs syndrome (RLS) and periodic limb movements in sleep (PLMS) are
      disorders that are common and disturbing to uremic patients. The treatment of
      these is problematic. Eight patients on chronic hemodialysis and continuous
      peritoneal dialysis completed a double-blind placebo-controlled crossover study
      using incremental doses of pergolide up to 0.25 mg at bedtime for treatment of
      RLS and sleep disruption. Five patients (62.5%) noted subjective improvement in
      restless legs symptoms and sleep quality. Objective results were improved only
      slightly by treatment. The percentage of the first hour in bed during which leg
      movements occurred decreased from 20.5 +/- 6.0 to 11.5 +/- 3.3, p < 0.05.
      However, findings during sleep were less positive. The following measures were
      not significant between placebo and treatment: leg movements per hour of sleep
      [53.7 +/- 22.3 vs 35.8 +/- 11.8 (p = 0.2)]; and percentage of sleep time spent
      with leg movements [5.5% +/- 3.2 vs 4.4% +/- 1.4 (p = 0.37)]. Patients continued
      to have very disrupted sleep, and we could not document an objective improvement
      in sleep architecture. Thus, although pergolide at the dose of 0.25 mg at bedtime
      provided subjective improvement in symptoms of restless legs and quality of
      sleep, and objectively decreased leg movements during the first hour in bed,
      objectively sleep continued to be disrupted. In this small patient group, the
      response to pergolide was not uniform, and further investigation is required to
      test effectiveness at higher doses.

PMID- 9779522
TI  - Nasal resistance in snorers with or without sleep apnea: effect of posture and
      nasal ventilation with continuous positive airway pressure.
AB  - We investigated the effects of posture and nasal ventilation with continuous
      airway pressure (CPAP) on nasal resistance in snorers with or without obstructive
      sleep apnea (OSA). Posterior rhinomanometry was performed in 70 snorers referred
      for polysomnography and in 11 nonsnoring volunteers, (1) in the seated posture;
      (2) and (3) after 10 minutes in the supine position, before and after inhalation
      of oxymetazoline; and (4) 10 minutes after return to the seated position. The
      effect of CPAP on posterior rhinomanometry was also examined in the nonsnorers
      and in 12 of the snorers. Changing from the seated to the supine position
      resulted in an increase in resistance in snorers and nonsnorers (resistance
      supine 182 +/- 10.9% and 128 +/- 6.7% respectively of seated value, p < 0.05).
      After oxymetazoline instillation, resistance in the supine position decreased but
      remained higher in snorers than baseline value in the seated position. Effects of
      posture and oxymetazoline were similar in snorers with or without sleep apnea.
      During nasal ventilation with CPAP, resistance was 30 +/- 3.8 and 45 +/- 4.4% of
      value before CPAP in snorers and nonsnorers, respectively (p < 0.05). These
      effects of posture and CPAP were also observed when resistance was measured with
      anterior rhinomanometry. In conclusion, nasal resistance measured with posterior
      rhinomanometry in the supine position is not predictive for OSA. Nasal
      ventilation with CPAP resulted in an acute and marked decrease in nasal
      resistance.

PMID- 9779523
TI  - Full polysomnography in the home.
AB  - STUDY OBJECTIVES: To evaluate unattended full polysomnography (PSG) recorded in
      the home by the DigiTrace Home Sleep System (DHSS) and to assess the ability to
      acquire, store and analyze polysomnographic data using the DHSS compared to
      standard paper PSG. DESIGN: Part 1 used a prospective, cross-over design. Part 2
      consisted of a prospective concurrent collection of polysomnographic data.
      SETTING: Sleep Disorders Center in a university medical center. PARTICIPANTS: All
      adult patients who required standard clinical PSG as part of their clinical
      evaluation, regardless of suspected diagnosis, except patients requiring video
      recording for abnormal behaviors. MEASUREMENTS AND RESULTS: The DHSS is a digital
      recording system with miniature preamplifiers and the capacity to record 18
      channels of polysomnographic data, including 4 channels of EEG (C3-A2, C4-A1, C3
      O1 and C4-O2), right and left EOG, two channels of chin EMG, ECG naso-oral
      airflow, respiratory effort (piezo crystal thoracic and abdominal belts and
      bilateral interacostal EMG), snore microphone, bilateral anterior tibialis EMG,
      and body-position sensor. In part 1,77 DHSS home recordings were evaluated. No
      recordings were lost due to equipment failure and each parameter was scorable in
      greater than 95% of all epochs. Most of the subjective assessments by
      questionnaire following each study revealed no difference between the two testing
      situations. However, patients reported more sleep time and a better overall test
      experience in the lab. Assessments of sleep quality and morning alertness
      compared to usual were rated higher in the lab. After completing both studies,
      more patients preferred the lab study (p < .01), mostly because of minor
      inconveniences and apprehension regarding acquisition of data during the home
      study. There was no difference in the assessment of which test most accurately
      represented their sleep. In Part 2, the DHSS recorded concurrently with paper PSG
      in the laboratory in 16 patients. The results show no significant differences for
      any parameter and strong positive correlations for all parameters. CONCLUSION:
      Using the DHSS, unattended full PSG can be performed in the home with reliable
      and high quality recordings. Full PSG can be extended to a larger patient
      population, because it is no longer limited by the number of beds, and there is a
      reduction in cost due to elimination of overnight staff and facility cost.

PMID- 9779524
TI  - Quantitative analysis of edema in the dorsal nerve roots induced by acute
      mechanical compression.
AB  - STUDY DESIGN: Edema in the dorsal nerve roots caused by acute compression was
      assessed quantitatively in the lumbar spine of the adult dog. OBJECTIVE: To
      establish quantitative evaluation of edema in the dorsal nerve roots and to
      observe changes after acute compression with time. SUMMARY OF BACKGROUND DATA:
      Mechanical compression induces an increase in microvascular permeability of the
      endoneurial capillaries and results in intraneural edema. However, there are no
      quantitative studies on edema in the nerve roots. METHODS: The seventh lumbar
      nerve root was compressed with a 60-g force clip for 10 minutes. The nerve roots
      were removed immediately and at 24 hours, 1 week, and 3 weeks after compression.
      Nerve roots from the control and the sham groups were also obtained. Before
      removing the nerve roots, Evans blue albumin was injected intravenously. Changes
      in edema were examined using fluorescence microscopy. Evans blue albumin emits a
      bright red fluorescence. The relative red fluorescent area was calculated using
      computer image analysis, and the data were used to indicate the degree of edema.
      RESULTS: In the compressed segment, edema was most pronounced just after
      decompression and reduced in nerves removed at 24 hours. In nerves removed at 1
      week, edema was pronounced but was reduced at 3 weeks. In the segments closest to
      the spinal cord, edema was seen after 1 week and was significant after 3 weeks.
      In the segments closest to the dorsal root ganglion, edema was not detected at
      any time. CONCLUSION: In the dorsal nerve roots the degree and the area of edema
      changed with time elapsed after acute compression. The degree of edema 24 hours
      after decompression was one third the degree immediately after decompression.
      These results show that edema induced by mechanical compression can recover after
      decompression.

PMID- 9779525
TI  - Importance of the intersegmental trunk muscles for the stability of the lumbar
      spine. A biomechanical study in vitro.
AB  - STUDY DESIGN: A biomechanical study was performed to determine the consequences
      of a simulation of muscle forces on the loads imposed on the functional spinal
      units. OBJECTIVES: No biomechanical study has investigated the effect of
      incorporation of agonist and antagonist muscle forces on the loading of
      functional spinal units. SUMMARY OF BACKGROUND DATA: Spinal disorders and low
      back pain are increasingly becoming a worldwide problem. Traditional conservative
      therapies are intended to strengthen the muscles of the trunk using a judicious
      regimen of physical exercises. METHODS: Eighteen whole, fresh-frozen human
      cadaveric lumbar spine specimens (L2-S2; average age, 53.4 years) were tested in
      a spine tester using pure flexion-extension, lateral bending, and axial moments.
      The effects of coactivation of psoas and multifidus muscles on L4-L5 mobility
      were simulated in vitro by applying two pairs of corresponding force vectors to
      L4. The segmental stability was defined by the correlation of an applied moment
      to the resultant deformation as shown in load-displacement curves, and the range
      of motion was defined as the angular deformation at maximum load. RESULTS: The
      coactivation of muscles was accompanied by a 20% decrease in the range of motion
      (i.e., a significant increase in stability) during lateral bending and axial
      moments. Application of flexion-extension moments and muscle coactivation
      resulted in a 13% increase in the sagittal range of motion. CONCLUSIONS: The
      action of the intersegmental agonist and antagonist muscles biomechanically
      increases the overall stiffness (stability) of the intervertebral joints in axial
      torque and lateral bending, whereas it may destabilize the segment in flexion.

PMID- 9779526
TI  - Biomechanical comparison of C1-C2 posterior fixations. Cable, graft, and screw
      combinations.
AB  - STUDY DESIGN: Four combinations of cable-graft-screw fixation at C1-C2 were
      compared biomechanically in vitro using nondestructive flexibility testing. Each
      specimen was instrumented successively using each fixation combination.
      OBJECTIVES: To determine the relative amounts of movement at C1-C2 after
      instrumentation with various combinations of one or two transarticular screws and
      a posterior cable-secured graft. Also to determine the role of each component of
      the construct in resisting different types of loading. SUMMARY OF BACKGROUND
      DATA: Spinal stiffness increases after instrumentation with two transarticular
      screws plus a posterior wire-graft compared with a wire-graft alone. Other C1-C2
      cable-graft-screw combinations have not been tested. METHODS: Eight human
      cadaveric occiput-C3 specimens were loaded nondestructively with pure moments,
      and nonconstrained motion at C1-C2 was measured. The instrumented states tested
      were a C1-C2 interposition graft attached with multistranded cable; a cable-graft
      plus one transarticular screw; two transarticular screws alone; and a cable-graft
      plus two transarticular screws. RESULTS: The transarticular screws prevented
      lateral bending and axial rotation better than the posterior cable-graft. The
      cable-graft prevented flexion and extension better than the screws. Increasing
      the number of fixation points often significantly decreased the rotation and
      translation (paired t test; P < 0.05). Axes of rotation shifted from their normal
      location toward the hardware. CONCLUSIONS: It is mechanically advantageous to
      include as many fixation points as possible when atlantoaxial instability is
      treated surgically.

PMID- 9779527
TI  - Effect of age and loading rate on human cervical spine injury threshold.
AB  - STUDY DESIGN: Statistical analysis of human cadaver cervical spine compression
      experiments. OBJECTIVES: To quantify the cervical spine compressive injury
      threshold as a function of the person's age, gender, and external loading rate.
      SUMMARY OF BACKGROUND DATA: Results of epidemiologic studies have indicated that
      most survivors of cervical spinal cord injury have spinal column fractures and
      dislocations that result from a compression or compression-flexion force vector.
      Cervical spinal column injury thresholds are dependent on many factors.
      Delineation of the injury thresholds according to age, gender, and loading rate
      is necessary to improve clinical assessments and prevention strategies. METHODS:
      Twenty-five human cadaver head-neck compression tests were included in the
      analysis. Two statistical models were used to quantify the effects of age,
      gender, and loading rate on the force required to induce failure in the cervical
      spine. A multiple linear regression model provided a direct equation that
      quantified the effects of the variables, and a proportional hazards model was
      used to quantify probability of injury with each factor. RESULTS: The regression
      model had a correlation coefficient of 0.87. There was an interactive effect
      between age and loading rate: Increasing age reduced the effect of loading rate
      and at approximately 82 years, loading rate had no effect. Men were consistently
      600 N stronger than women. The 50% probability of failure for a 50-year-old man
      at a 4.5-m/sec loading rate was approximately 3.9 kN. Differences in probability
      curves followed the same trends as seen in the regression model. CONCLUSIONS: The
      effects of age on cervical spine injury threshold are coupled with the rate of
      loading experienced through the external force vector that causes the trauma.
      Assessment of injury mechanisms and thresholds should be based on the person's
      age, gender, and loading rate to determine treatment and prevent injuries.

PMID- 9779528
TI  - Treatment of stable burst fracture of the atlas (Jefferson fracture) with rigid
      cervical collar.
AB  - STUDY DESIGN: A retrospective review of a clinical series. OBJECTIVE: To evaluate
      the use of a rigid cervical collar alone as the treatment for stable Jefferson
      fracture, and to devise an algorithm for treatment of Jefferson fracture with or
      without an associated cervical injury. SUMMARY OF BACKGROUND DATA: The
      traditional treatment for Jefferson fracture, if there is no indication for
      surgery, is immobilization by halo vest. Because halo vest placement is
      associated with intracranial infection and a significant degree of patient
      discomfort, slightly less rigid forms of external immobilization may be useful
      for the treatment of stable Jefferson fractures. No standard protocol calling for
      the use of one form of stabilization device has been reported. MATERIALS: The
      medical records and radiographs of 16 consecutive patients with Jefferson
      fracture during a 2-year period were reviewed. Each patient underwent a complete
      cervical radiograph series and a computed tomographic scan. The mean C1 lateral
      mass displacement was 1.8 mm. Cervical spine radiographs, including lateral
      flexion-extension views were obtained 10 to 12 weeks after injury before the
      removal of an external immobilization device. RESULTS: Of these 16 patients, 1
      sustained a complete injury, and 7 sustained an incomplete injury. Eight patients
      were neurologically intact. Twelve patients sustained a stable Jefferson fracture
      and were treated with a rigid cervical collar (Miami-J collar [Jerome Medical,
      Moorestown, NJ]) alone from 10 to 12 weeks. The patient sustaining the complete
      neurologic injury died of multisystem trauma. All 15 live patients showed no
      instability on their follow-up plain radiographs before the removal of an
      external stabilization device. Six patients underwent further plain radiographs
      approximately 1 year after the fracture and similarly demonstrated no
      instability. CONCLUSIONS: Isolated stable burst fracture of the atlas can be
      treated effectively with a rigid cervical collar alone for 10 to 12 weeks with
      good neurologic recovery and segmental stability. Unstable Jefferson fractures
      with concurrent unstable fracture of other cervical vertebrae, especially C2,
      requires surgical stabilization.

PMID- 9779529
TI  - The anatomic location of the dorsal ramus of the cervical nerve and its relation
      to the superior articular process of the lateral mass.
AB  - STUDY DESIGN: This study analyzed the anatomic relation of the dorsal ramus of
      the cervical spinal nerve to the lateral mass. OBJECTIVES: To determine the
      location of the dorsal rami of the cervical spinal nerves from C3 to C7 in
      relation to the superior articular processes of the lateral masses. SUMMARY OF
      BACKGROUND DATA: The anatomic study of the cervical spinal nerve and its
      relations to adjacent bony structures have been addressed. No previous anatomic
      study with regard to the location of its dorsal ramus relative to the lateral
      mass has been reported. METHODS: Twelve specimens were obtained for study of the
      dorsal rami of the cervical spinal nerves. All soft tissues surrounding the
      cervical spinal nerves from C3 to C7 were dissected from the intervertebral
      foramens until the dorsal rami were clearly exposed. The facet joints in the
      corresponding levels were then opened by removal of the capsules. Three
      measurements, including the height of the dorsal ramus, the distance between the
      dorsal ramus and the tip of the superior articular facet, and the angle of the
      dorsal ramus relative to the superior articular surface, were taken for each
      ramus. RESULTS: The results showed that the mean height of the dorsal ramus for
      both sides decreased progressively from C3 (2.2 +/- 0.6 mm) to C7 (1.2 +/- 0.2
      mm). The mean distance between the dorsal ramus and the tip of the superior facet
      showed an inconsistent change, with the maximum value seen at C5 (7.4 +/- 1.6 mm)
      and the minimum at C7 (5.5 +/- 2.9 mm). The mean angle of the dorsal ramus
      relative to the superior articular facet ranged from 23.3 degrees +/- 14.3
      degrees to 29.8 degrees +/- 11.2 degrees. CONCLUSIONS: The dorsal ramus of the
      cervical spinal nerve is closer to the anterolateral corner of the base of the
      superior articular processes. Lateral mass screws directed to the anterolateral
      corner of the base of the superior articular process should be avoided.

PMID- 9779531
TI  - Interrater and intrarater reliability in the measurement of kyphosis in
      postmenopausal women with osteoporosis.
AB  - STUDY DESIGN: A reliability study was performed using repeated random
      measurements involving three observers, 26 subjects and three instruments.
      OBJECTIVES: To determine the most reliable, cost-effective, noninvasive, and
      clinically feasible method of measuring spinal kyphosis. SUMMARY OF BACKGROUND
      DATA: The most clinically useful, noninvasive and reliable method of measuring
      postural deformity in spinal osteoporosis (kyphosis) remains unqualified. Despite
      traditional use of costly, invasive roentgenographs for the evaluation of spinal
      kyphosis, the reliability of this method remains questionable. METHODS: Twenty
      six postmenopausal women with known bone mineral density and a diagnosis of
      osteoporosis were recruited from the Osteoporosis Program at Women's College
      Hospital, Toronto, Canada. Non-invasive measurements of thoracic kyphosis were
      obtained by three trained examiners using the DeBrunner's kyphometer and the
      flexicurve ruler. The intrarater and interrater reliability of and between each
      method was compared, using roentgenographic films obtained in the sagittal plane.
      Spinal posture was classified according to the method of Itoi (1990). Statistical
      computations were performed using SAS statistical software. RESULTS: Consistent
      measurements were obtained with the DeBrunner's kyphometer and the flexicurve
      ruler by each observer, according to the results of critical two-way analysis of
      variance (Intraclass Correlation Coefficient 2, 1). Measurements in two
      subgroups, healthy backs (n = 11) and rounded backs (n = 13), showed consistent
      use of each noninvasive instrument with some examiner preference for specific
      tools. There was marginally better intrarater and interrater reliability using
      the DeBrunner's kyphometer compared with that obtained with the flexicurve ruler.
      Two-way analysis of variance (Intraclass Correlation Coefficient 2, 1) of
      collapsed data showed no significant difference in the reliability of the
      kyphometer, flexicurve ruler, or roentgenographs in the measurement of thoracic
      kyphosis. CONCLUSIONS: The flexicurve ruler and DeBrunner's kyphometer had the
      closest agreement in the measurement of spinal kyphosis. The kyphometer
      demonstrated the least variation in intrarater and interrater reliability when
      compared with the flexicurve ruler and roentgenographs. The flexicurve ruler
      permits qualitative assessment of posture, however, and is the most cost
      effective instrument. The results of this study challenge the traditional belief
      that roentgenographic analysis is the best method for evaluating spinal kyphosis.
      The DeBrunner's kyphometer and flexible ruler may represent viable, cost
      effective and noninvasive alternatives to roentgenographic evaluation of spinal
      kyphosis.

PMID- 9779530
TI  - Capacity of the clinical picture to characterize low back pain relieved by facet
      joint anesthesia. Proposed criteria to identify patients with painful facet
      joints.
AB  - STUDY DESIGN: Prospective randomized study to compare the efficacy of facet joint
      injection with lidocaine and facet joint injection with saline in two groups of
      patients with low back pain, with and without clinical criteria that were
      determined in a previous study to implicate the facet joint as the primary source
      of the pain. OBJECTIVES: To assess the efficacy of single facet joint anesthesia
      versus placebo (saline injections) and to determine clinical criteria that are
      predictive of significant relief of LBP after injection. SUMMARY OF BACKGROUND
      DATA: There is no syndrome that discriminates between lower back pain caused by
      facet joint and that caused by other structures. Single or double facet joint
      anesthesia, and single photon emission computed tomography are expensive and time
      consuming procedures for selecting patients in controlled clinical trials with
      large populations. METHODS: Results of a previous study showed that seven
      clinical characteristics were more frequent in patients who responded to facet
      joint anesthesia than in those who did not. In the current study, a group of 43
      patients with lower back pain who met at least five criteria were compared with
      37 patients who met fewer criteria. Patients randomly received injection of
      either lidocaine or saline into the lower facet joints. The result was considered
      positive if more than 75% pain relief was determined by visual analog scale. The
      patient, the radiologist, and the investigator were blinded. An analysis of
      variance was used to seek an interaction between clinical group effect and
      injection effect, and logistic regression analysis to select the best set of
      variables that would be predictive of minimum pain relief of 75% after the
      injection. RESULTS: There was a significant interaction between clinical group
      and injection effect (P = 0.003). In patients with back pain, lidocaine provided
      greater lower-back pain relief than saline (P = 0.01). Lidocaine also-provided
      greater pain relief in the back pain group than in the nonpain group (P = 0.02).
      The presence of five among seven variables (age greater than 65 years and pain
      that was not exacerbated by coughing, not worsened by hyperextension, not
      worsened by forward flexion, not worsened when rising from flexion, not worsened
      by extension-rotation, and well-relieved by recumbency), always including the
      last item, distinguished 92% of patients responding to lidocaine injection and
      80% of those not responding in the lidocaine group. CONCLUSIONS: A set of five
      clinical characteristics can be used in randomized studies to select lower back
      pain that will be well relieved by facet joint anesthesia. These characteristics
      should not, however, be considered as definite diagnostic criteria of lower back
      pain originating from facet joints.

PMID- 9779532
TI  - Increase in sick leave rates caused by back pain among pregnant Swedish women
      after amelioration of social benefits. A paradox.
AB  - STUDY DESIGN: A retrospective population study. OBJECTIVES: To explore whether
      the increase in social benefits for pregnant women introduced in Sweden between
      1978 and in 1986 was associated with a decrease in the use of sick leave caused
      by back pain during the same period. SUMMARY OF BACKGROUND DATA: Back pain is a
      common condition among Swedish pregnant women. It may be regarded as a normal
      discomfort of pregnancy, because at least 50% of pregnant women experience back
      pain to some extent during pregnancy. METHODS: Participants were women
      consecutively delivered in 1978 (n = 1524) and in 1986 (n = 1688). Between these
      two time points, the number of offered days of parental benefit increased and a
      new benefit, the pregnancy benefit, was introduced. Data were collected from the
      antenatal care and delivery records and from pregnant women's social insurance
      files. RESULTS: From 1978 to 1986 the use of sick leave because of back pain
      during pregnancy increased. The number of pregnant women granted sick leave
      employed pregnant women because of back pain increased from 11% in 1978 to 29% in
      1986 (P < 0.001). The sick leave rate increased in most occupations and
      especially among young women. CONCLUSIONS: The Swedish society has provided ample
      social benefits to allow the pregnant woman to take leave from work, without
      having to be labeled as "ill," because of normal conditions such as back pain
      during pregnancy. Instead of an expected decrease in sick leave because of back
      pain during pregnancy, an increase was observed.

PMID- 9779533
TI  - A report from the Second International Forum for Primary Care Research on Low
      Back Pain. Reexamining priorities.
AB  - STUDY DESIGN: Consensus process. OBJECTIVES: Reexamining and redirecting the
      research agenda for low back pain in primary care. SUMMARY OF BACKGROUND DATA:
      Most research, publications, and funding have traditionally been directed toward
      specialty and biologically oriented investigations of "spinal disorders" from
      biomedical and biomechanical perspectives. Beginning in the mid-1980s, primary
      care researchers began to investigate this field in earnest, focusing on lower
      back pain as a pain syndrome within an individual, family, and community context.
      Unfortunately, more progress has been made on what should not be done in
      diagnosing and treating lower back pain than on what should be done. METHODS:
      This was a modified group process designed to reach consensus among an
      international group of primary care lower back pain researchers. RESULTS: Nearly
      all of the research priorities from the initial 1995 forum are still thought to
      be important, although only modest progress has been made on most of them. The
      priorities perceived to be the most feasible to investigate and the ones in which
      the greatest strides have been achieved are in methodologic rather than
      substantive areas. Identifying subgroups of people with lower back pain is still
      given top ranking in 1997, but the priorities have changed dramatically. Greater
      emphasis is given to finding predictors and risk factors for lower back pain
      chronicity, improving self-care strategies, and stimulating self-reliance. New
      items now make up 50% of the top 10 priorities. In general, the additions reflect
      a greater emphasis on expanding methodologic avenues of inquiry. CONCLUSIONS:
      Methodologic advances, the enlistment of new techniques and disciplines, and
      redirected research efforts may facilitate progress in the diagnosis and
      treatment of lower back pain.

PMID- 9779534
TI  - Primary care research on low back pain. The state of the science.
AB  - The past few years have witnessed an explosion of primary care-relevant research
      on low back pain. The descriptive studies have helped elucidate the diagnostic
      and therapeutic interventions that are in current use. The literature syntheses
      have clarified what is known about the usefulness of these interventions. The
      randomized trials have pushed the frontiers of knowledge in several important
      areas. The quality of research in this field is mixed but has improved
      significantly in recent years. If research is to lead to substantial improvements
      in primary care for low back pain, however, the focus must be broadened to
      embrace an existing but neglected paradigm, the biopsychosocial model. It must be
      understood how the physician can become a more effective healer and counselor for
      the patient with back pain. This will require that greater attention be paid to
      literature outside of the field and that communication and collaboration with
      researchers in other disciplines increase. Modern distractions such as
      technology, litigation, and disability compensation have interfered with the
      ability of physicians to meet their patients' needs. If physicians are to become
      more effective managers of such common problems as low back pain, they must
      rediscover their ability to help their patients cope with illness and suffering.

PMID- 9779536
TI  - Methodologic issues in low back pain research in primary care.
AB  - STUDY DESIGN: Narrative review and discussion of the selected literature.
      OBJECTIVES: To discuss some important methodologic challenges in low back pain
      research in primary care. SUMMARY OF BACKGROUND DATA: Many methodologic problems
      must be confronted when conducting low back pain research. Some of these problems
      are back pain specific or specific to the primary care setting. METHODS:
      Methodologic problems related to four research issues will be discussed: study
      designs, definition of low back pain, determinants of low back pain, and outcome
      assessment. RESULTS: Two fundamentally different study designs are frequently
      used in low back pain research, namely observational studies and experimental
      studies. The definition of low back pain is typically restricted to a highly
      variables self-reported symptom, the sensation of pain in the back. There clearly
      is a need for an evidence-based classification system for low back pain. Because
      a tenable theoretical framework is lacking, it is difficult to know which
      determinants of low back pain should be quantified. Low back pain studies focus
      usually on health-related quality-of-life outcome parameters. The identification
      of the minimum clinically relevant changes for the most important outcome
      instruments needs further consideration. CONCLUSIONS: In years to come, low back
      pain researchers are challenged to overcome some of these (and other) problems to
      enhance the quality of low back pain research in primary care.

PMID- 9779535
TI  - Outcome measures for low back pain research. A proposal for standardized use.
AB  - STUDY DESIGN: An international group of back pain researchers considered
      recommendations for standardized measures in clinical outcomes research in
      patients with back pain. OBJECTIVES: To promote more standardization of outcome
      measurement in clinical trials and other types of outcomes research, including
      meta-analyses, cost-effectiveness analyses, and multicenter studies. SUMMARY OF
      BACKGROUND DATA: Better standardization of outcome measurement would facilitate
      comparison of results among studies, and more complete reporting of relevant
      outcomes. Because back pain is rarely fatal or completely cured, outcome
      assessment is complex and involves multiple dimensions. These include symptoms,
      function, general well-being, work disability, and satisfaction with care.
      METHODS: The panel considered several factors in recommending a standard battery
      of outcome measures. These included reliability, validity, responsiveness, and
      practicality of the measures. In addition, compatibility with widely used and
      promoted batteries such, as the American Academy of Orthopaedic Surgeons Lumbar
      Cluster were considered to minimize the need for changes when these instruments
      are used. RESULTS: First, a six-item set was proposed, which is sufficiently
      brief that it could be used in routine care settings for quality improvement and
      for research purposes. An expanded outcome set, which would provide more precise
      measurement for research purposes, includes measures of severity and frequency of
      symptoms, either the Roland or the Oswestry Disability Scale, either the SF-12 or
      the EuroQol measure of general health status, a question about satisfaction with
      symptoms, three types of "disability days," and an optional single item on
      overall satisfaction with medical care. CONCLUSION: Standardized measurement of
      outcomes would facilitate scientific advances in clinical care. A short, 6-item
      questionnaire and a somewhat expanded, more precise battery of questionnaires can
      be recommended. Although many considerations support such recommendations, more
      data on responsiveness and the minimally important change in scores are needed
      for most of the instruments.

PMID- 9779537
TI  - Chronicity of back problems during working life.
AB  - STUDY DESIGN: A follow-up study of a cohort of 444 patients aged 16 to 59 years
      who consulted with their general practitioners (GPs) in 1987-1988 for an incident
      episode of back pain. OBJECTIVES: To determine the proportion of patients with
      back pain in whom chronic back problems develop after a follow-up of 7 years, to
      compare health outcomes and labor force participation of patients with and
      without chronic back problems and to identify determinants of chronicity. SUMMARY
      OF BACKGROUND DATA: The incidence and prevalence of back pain are very high. A
      large proportion of the costs related to medical consumption, absence from work,
      and disability are probably caused by chronic back problems. It is unknown what
      proportion of back problems become chronic, especially after a long follow-up
      period, and which factors can predict chronicity. METHODS: Data on the course of
      the symptoms and medical consumption from the period between 1987-1988 and 1991
      were gathered retrospectively. Data on several health outcomes, including LFP,
      and data on some work characteristics were collected prospectively in 1991. A
      more extensive data set on health outcomes including psychologic status and
      working situation was collected in 1994. RESULTS: Chronic back problems developed
      in 28% of the patients. These patients reported more pain, higher levels of
      medical resource consumption, worse health outcomes, and lower labor force
      participation. Episodes of back pain before 1987-1988, severe pain in 1991, and
      disability score in 1991 were positively associated with chronicity in 1994,
      difficulties with job performance in 1991, and frequent stooping in the subgroup
      of patients who held a paying job in the follow-up period. CONCLUSIONS: Even
      after a follow-up of 7 years, the proportion of people with chronic back problems
      was high. The consequences for quality of life, labor force participation, and
      consumption of medical resources are clear. Further research is necessary to
      examine determinants and ways to prevent chronicity.

PMID- 9779538
TI  - Posterior approach with Louis plates for fractures of the thoracolumbar and
      lumbar spine with and without neurologic deficits.
AB  - STUDY DESIGN: This is a retrospective revue of the long-term outcome of posterior
      Louis plate fixation for the treatment of irreducible or ligamentously unstable
      fractures of the thoracolumbar and lumbar spine with or without neurologic
      deficit. OBJECTIVES: To determine the clinical, radiologic, and functional status
      of patients who underwent posterior fracture fixation with Louis plates and to
      evaluate the effect of instrumentation length on the construct's ability to
      maintain reduction of the fracture. SUMMARY OF BACKGROUND DATA: Since the
      development of pedicle screw fixation described by Roy-Camille, there has been a
      rapid evolution in the number and complexity of systems available for posterior
      spinal stabilization. Along with this escalation in implant and instrument
      sophistication, there has been a corresponding increase in implant cost. To date,
      no series has been reported of the clinical, radiologic, and functional results
      of posterior instrumentation with semirigid Louis plates for spinal fractures.
      METHODS: A retrospective review of spinal fractures from T11 to L5 treated since
      1985 by posterior plate fixation showed that 56 patients (37 men and 19 women)
      with an average age of 34 years and a minimum follow-up of 2 years (average, 41
      months) were available for review. There were 36 burst fractures, 4 Chance
      fractures and 16 fracture-dislocations treated. Forty-three patients had
      neurologic injury. RESULTS: Before surgery, vertebral kyphosis averaged 15
      degrees, improved to 5 degrees with reduction, and reached a steady 10 degrees at
      final follow-up. Similarly, corrected kyphosis initially averaged 12 degrees but
      improved to 0.5 degree with reduction, and was 10 degrees at final follow-up.
      Vertebral canal compromise initially averaged 50% but was reduced to 13% with
      surgery and 6% at 1 year. There was no significant difference between the ability
      of short and long constructs to maintain reduction. Eighty-eight percent of
      patients with neurologic injury improved at least one Frankel grade with
      treatment. Functional and pain evaluation by the Denis scale showed 25 patients
      rated P1, 25 rated P2, and 6 rated P3. Twenty-eight were rated W1, 16 were W3,
      and 12 were W5 at last follow-up. CONCLUSIONS: Fractures of the thoracolumbar
      spine can be treated effectively with the semirigid Louis plating system. Because
      of its low cost and ease of insertion, the Louis system is an excellent choice
      for short arthrodesis and instrumentation of these fractures. Although there is
      some loss of reduction when compared with more rigid systems, there is no
      functional compromise in these patients.

PMID- 9779539
TI  - Canine dental disease.
AB  - The key to veterinary dentistry is recognition of veterinary dental disease. This
      article is intended as an introduction to oral disease. Starting with the teeth
      themselves, this overview will progress to the supporting tissues and remaining
      oral structures.

PMID- 9779540
TI  - The effects of dental disease on systemic disease.
AB  - Chronic exposure to periodontal pathogens results in the continued stimulation of
      an immune and nonimmune response by the host. The cytokines and other
      inflammatory mediators produced in gingivitis/periodontitis result in local
      tissue destruction and may reach significant levels affecting the cardiovascular
      system or placental tissues. The oral cavity may also serve as a direct reservoir
      for bacterial contamination of the lungs with subsequent development of bacterial
      pneumonia.

PMID- 9779541
TI  - Oral-dental radiographic examination technique.
AB  - In general practice, dental radiography is currently being performed more often
      as a treatment planning technique during routine dental prophylactic procedures
      than ever before. Medical radiography units, although still useful for the
      determination of bone cancer, mineral deficiencies, and fracture studies, are
      yielding to the use of more versatile dental radiograph machines that are being
      installed in the dental operatory and expose only the dental film. Currently, the
      technology of intraoral digital radiography, photography, and videography is
      available. Digital images can be enhanced, preserved on Polaroid film, or stored
      directly into computer data banks, without the use of dental film. This article
      acquaints the reader with digital technology, but deals primarily with
      traditional film-based oral-dental radiographic examination technique. The
      equipment and techniques described are affordable and well within the
      capabilities of the general practitioner. The importance of being able to produce
      dental radiographs of excellent quality is basic when providing competent dental
      care.

PMID- 9779542
TI  - Radiographic evaluation.
AB  - The bulk of the tooth, that is, the root and most of the periodontium, can be
      visualized only by means of radiographs. Consequently, a lot of pathology remains
      undiscovered if clinical examination does not involve radiography. Although
      lesions such as caries can be recognized without radiography, the full extent of
      the lesions, and whether pulpal and periapical involvement is present as a
      consequence, cannot be assessed. In other words, a clinical examination is not
      complete without radiography. Periodontal disease, endodontic disease, caries,
      resorptive lesions, fractures, bone pathology, and neoplastic conditions all
      require radiography for a more complete diagnosis, thus allowing optimal planning
      of treatment. It is also necessary to know the normal radiographic anatomy to be
      able to identify the abnormal. Moreover, many dental procedures can be carried
      out only under radiographic control. Checking adequacy of procedures and success
      of treatment relies heavily on radiography. In short, radiographs are required to
      reach a diagnosis and thus plan treatment optimally, to be able to perform
      certain procedures, and to be able to assess the outcome of treatment performed.
      Practicing dentistry without using radiography as a tool would be considered
      negligent in human dentistry. In the author's opinion, the same would apply to
      veterinary dentistry.

PMID- 9779543
TI  - Periodontal disease in dogs. Etiopathogenesis, prevalence, and significance.
AB  - Periodontal disease is very common and often very severe in dogs. It is caused by
      accumulation of bacterial plaque, particularly Gram-negative anaerobic rods.
      Tissue destruction results from autodegradation induced by the continuing
      inflammatory response. Small dogs are particularly at risk. Prevention by
      retarding accumulation of plaque is the key concept.

PMID- 9779544
TI  - Prevention of periodontal disease.
AB  - Periodontal disease is the most common disease affecting adult dogs and cats. It
      is also a very preventable disease. The insidious nature of the disease and
      requirement for the pet owner to be actively involved make client and public
      education absolutely vital. Although clients are commonly aware of their pets'
      bad breath, they rarely notice gingivitis, fractured teeth, and traumatic
      malocclusions. The annual National Pet Dental Health Month program has resulted
      in a tremendous increase in public awareness. Veterinarians must carry this
      further in their everyday practices, convincing our clients of the need for
      preventive dental care. It is only through clients' ongoing desire and
      persistence that a long-term preventive program can be successful. This requires
      a coordinated effort by the entire hospital staff. When successful, clients' pets
      will live healthier and longer lives.

PMID- 9779545
TI  - Treatment of periodontal disease.
AB  - Periodontal surgery is used to control advanced lesions affecting the support for
      teeth. The choice between conservative treatment and surgical treatment is a
      technical issue, but client compliance plays an important role. Excision surgical
      techniques (e.g., gingivectomy) and incisional surgical techniques (e.g., flap
      surgery) are described in this article. Postoperative, recall, and retreatment
      programs are explored.

PMID- 9779546
TI  - Oral and periodontal tissue. Maintenance, augmentation, rejuvenation, and
      regeneration.
AB  - This article discusses the controversies, usefulness, and limitations of oral and
      periodontal tissue maintenance, augmentation, rejuvenation, and regeneration in
      the dog and cat. It details many of the specialized materials and techniques used
      in these procedures in attempts to re-establish healthy conditions within the
      periodontium. Bone loss following tooth extraction is discussed with
      consideration as to which teeth should have alveolar ridge maintenance procedures
      and the important reasons as to why. Radiographs show the degree of improvement
      demonstrated in treatment of various cases involving bone loss from periodontal
      disease, treatment of bone injuries with oral fractures and their prevention.

PMID- 9779547
TI  - Endodontic diagnosis in dogs.
AB  - Complete endodontic evaluation should diagnose endodontic involvement, provide a
      treatment plan, and evaluate the true success or failure probabilities.
      Evaluation of the age, physical and oral health of the patient, the endodontic
      anatomy, clinical and radiographic findings can provide a treatment plan and a
      predictable prognosis.

PMID- 9779548
TI  - Endodontic therapy in the veterinary patient.
AB  - Standard root canal therapy is more clearly described as conventional
      endodontics. Most modern endodontic treatment involves removal of the
      irreversibly damaged pulp followed by cleaning and shaping of the root canal
      space and subsequent filling, or obturation, with a semisolid material and a
      sealer. A general increase in awareness of the benefits of veterinary endodontics
      has created a rise in the demand for endodontic procedures that help to retain
      the teeth longer. This article on endodontic therapy includes endodontic anatomy,
      diagnosis of endodontic disease, pulpectomy techniques of access preparation,
      canal preparation and filling the canal, partial coronal pulpectomy, and
      treatment of the open apex. Familiarity of the techniques covered in this article
      and with advances in veterinary endodontics have become necessary for the
      veterinary dental practitioner.

PMID- 9779549
TI  - Newer endodontic therapeutic treatment.
AB  - Current concepts of endodontic treatment have changed over the years; however,
      the fundamental principles remain constant. We in the veterinary field have seen
      rapid technological advances in the field of human endodontics that we have tried
      to adapt to our patients. Veterinary endodontists must continually evaluate new
      instruments, devices, and procedures with the overall goal in mind: to give the
      patient the best care possible by proper diagnosis, removal of intracanal
      irritants, and creation of an environment suitable for healing. The design is not
      as important as how the instrument is used. As a result, keep in mind patience,
      prudence, and practice. All instruments and techniques have limitations, but the
      most important limitation is within ourselves.

PMID- 9779550
TI  - Composite restorative dentistry.
AB  - Modern composite restorative materials offer the veterinarian greater flexibility
      in the repair of damaged teeth. An understanding of the make-up of these
      materials is essential to maximize the effectiveness of the repairs. Endodontic
      disease was once ignored and is now treated on a daily basis. Newer composite
      restorations offer an effective means of protecting the sensitive pulp from
      bacterial invasion and allow the veterinarian to restore the tooth to function.

PMID- 9779551
TI  - Restorative dentistry. Crown therapy.
AB  - Not one post, core, margin, impression material, cement, or final restoration can
      be used in all clinical situations. This article does not discuss the merits and
      shortcomings of the numerous restorative concepts and techniques that exist, but
      rather has concentrated on those that the author believes are valid and
      applicable today. If one third or more of the anatomic crown remains, or if this
      is achieved by crown lengthening, a post may not be necessary; however, a crown
      restoration should definitely be considered. Veterinary dentistry cannot limit
      those variables that occur daily in clinical practice. Veterinarians must learn
      to work with these variables and spend less time trying to find the one that
      applies to all cases. When the basic concepts of how to retain the various
      restorative components and how to protect remaining tooth structure are
      understood, the ability to answer numerous questions that arise during the
      restorative process is facilitated and results in final restorations that are
      based on sound design principles.

PMID- 9779552
TI  - Maxillofacial surgery.
AB  - Maxillofacial surgery in dogs includes the management of jaw fractures various
      palatal surgical procedures, the management of oral tumors, and the surgical
      management of miscellaneous maxillofacial problems. Miscellaneous maxillofacial
      problems that may require surgical intervention include dentigenous cysts, bone
      sequestra or osteomyelitis, and an inability to open or close the month. Careful
      perioperative planning of maxillofacial surgical procedures will help ensure a
      successful outcome.

PMID- 9779553
TI  - Exodontics.
AB  - Exodontic therapy may be challenging and difficult especially if the involved
      tooth has minimal or no periodontal disease. Surgical methods aid the clinician's
      ability to perform exodontic therapy for the maxillary fourth premolar,
      mandibular first molar, maxillary canine, and mandibular canine. Complications of
      exodontic therapy may include fracture, ocular trauma, and infection.

PMID- 9779554
TI  - [Pathogenic power of Salmonellae: virulence factors and study models].
AB  - Salmonellae are potentially pathogenic for humans as well as for numerous animal
      species. They possess numerous virulence factors, which allow them to adapt to
      various environmental conditions and to host response at each step of the
      pathogenic process. Key-steps such as the invasion of epithelial cells or
      survival within macrophages have been extensively studied. These studies have led
      to the discovery of an original protein secretion system and have demonstrated
      the existence of pathogenicity islands. This considerable progress is due to the
      development of numerous in vitro and in vivo models and of new identification
      strategies for the implicated genes. Recently, many original and elegant
      strategies have been recently proposed.

PMID- 9779555
TI  - Impact of liposomes as delivery systems in veterinary medicine.
AB  - The development of drug resistance and the inability of the drug to reach the
      location of the etiologic agents are major challenges for anti-infective and
      cancer therapies. As the development of new drugs with improved pharmacodynamic
      and pharmacokinetic properties is a slow and difficult process, drug delivery
      systems appear as promising alternatives. Liposomes are lipid vesicles formed
      when phospholipids are exposed to an aqueous environment. They arrange themselves
      in bilayers and close up, forming a vesicle. During this process they capture the
      aqueous phase of the dispersion, and any substance dissolved in it, within the
      vesicle. Liposomes have remarkable features that make them an almost ideal
      delivery system. They are biodegradable, with few side effects, can deliver drugs
      with different physico-chemical properties together and can be formulated for
      different routes of administration. The potential to modify the pharmacokinetic
      behaviour of encapsulated drugs to deliver them selectively to the site of action
      is the most important feature of liposomes as drug delivery systems. Liposomes
      are already used in human medicine for he treatment of bacterial, viral and
      parasitic diseases, and cancer. They have also been proven useful as
      immunoadjuvants and vaccines. Liposomes are used in certain avian vaccines. The
      possible uses of liposomes and their impact in veterinary medicine in the
      treatment of infectious diseases and cancer as well as in the prevention of
      diseases are discussed in the present article.

PMID- 9779556
TI  - An RT-PCR assay for the specific detection of classical swine fever virus in
      clinical samples.
AB  - A simple reverse transcriptase-polymerase chain reaction (RT-PCR) assay has been
      developed for the specific amplification of DNA after reverse transcription of
      RNA from the classical swine fever virus (CSFV). A pair of oligonucleotides was
      selected from an area of high homology in the genome of CSFV strains, but which
      differed from the corresponding sequences in the genome of bovine viral diarrhea
      virus (BVDV) strains. Using these primers (CSFV1-CSFV2), a CSFV specific DNA band
      of 174 bp was amplified from the CSFV RNA extracted from four reference strains
      and 14 field isolates, as well as from 25 organ extracts and eight buffy coats
      and serum samples of experimentally infected animals. No amplification was
      observed with the RNA from four BVDV reference and vaccine strains and seven
      field isolates. This RT-PCR assay made it possible, in a one-step reaction, to
      detect CSFV rapidly, sensitively and specifically in cell culture supernatants
      and in clinical specimens.

PMID- 9779557
TI  - In vivo studies on lysosubtilin. 3. Efficacy for treatment of mastitis and
      superficial lesions of the udder and teats in cows.
AB  - Lysosubtilin is a broad-spectrum preparation of lytic enzymes from Bacillus
      subtilis designed for veterinary medicine. This study demonstrates its efficacy
      for the treatment of reproductive system diseases (mastitis, superficial lesions
      of the udder and teats) in cows. Prior to determination of optimal therapeutic
      doses, samples taken from the milk and udder skin of sick animals were examined
      microbiologically. The examinations revealed a high incidence of polymicrobial
      infections (26.9 and 84.9% for mastitis and superficial udder lesions,
      respectively) caused by various mixtures of bacteria (both Gram-positive and Gram
      negative) and fungi/yeasts. Dose determination studies involved 115 cows with
      clinical signs of mastitis. The optimal dose for mastitis treatment was found to
      be 3.5 x 10(6) U lysosubtilin dissolved in 100 mL of distilled water, which was
      then administered into the mammary gland via the teat canal once daily until
      recovery. Such a dose yielded statistically significant decreases (P < 0.05) both
      in the length of time before clinical recovery (2 d versus 4 and 4.5 d with
      either of the two antibiotic-based traditional drugs) and in the percentage of
      animals who suffered relapses within a 2-month period following treatment (5%
      versus 60%, with one of the two drugs). A field experiment involving 106 cows was
      designed to compare the efficacy of 1% lysosubtilin water-glycerin solution (1:9
      v/v) and other traditional medications for the topical treatment of superficial
      lesions of the udder and teats as well as its potential for mastitis prevention.
      All drugs used yielded a 100% cure rate, but lysosubtilin application made it
      possible to achieve a statistically significant decrease (P < 0.05) in the
      duration of the recovery period (2.5 d versus 4.5 to 5.5 d) when compared with
      any of the four other drugs tested. Its efficacy for mastitis prevention was at
      least 3.4 times higher than the efficacy of the other medications used
      (statistically significant, P < 0.05, with regards to two of the four drugs) as
      well. We therefore conclude that lytic enzyme preparations are prospective
      antimicrobial drugs and when used to combat animal diseases they may serve as a
      possible alternative to common antibiotics.

PMID- 9779558
TI  - Cytokeratin immunostaining in normal dog major and minor salivary glands.
AB  - Immunohistochemical staining, with a monoclonal antibody specific for
      cytokeratins 5, 6, 8, 17 and 19 of dog submandibular, sublingual, parotid,
      palatine, tongue and zygomatic salivary glands resulted in staining of
      myoepithelial cells, duct epithelial cells (including intercalated, striated and
      secretory ducts) and some acinar epithelial cells. Differences in acinar staining
      between glands reflected the predominance of serous or mucous cells. Acinar
      epithelial staining was confined to serous cells in sublingual and zygomatic
      glands and in some parotid glands; serous cells in other parotid glands, and
      serous demilunes in submandibular, tongue and palatine glands, were unstained.
      Mucous cells were not stained in any of the glands.

PMID- 9779559
TI  - Specific cytotoxic lymphocyte response in swine against structural proteins of
      transmissible gastro-enteritis virus: a study using lymphoblastoid cell line and
      recombinant vaccinia virus.
AB  - To determine the specificity, if any, of cellular cytotoxicity against
      transmissible gastro-enteritis virus (TGEV) infected cells, we developed a test
      using B lymphoblasts from a MHC histocompatible (d/d haplotype) cell line (L14),
      as stimulating and target cells. These cells were previously infected with
      recombinant vaccinia virus including different TGEV structural genes, either the
      spike (vS), membrane (vM) or nucleoprotein gene (vN). Lymphocytes from a TGEV
      immunized (d/d) swine developed a cytotoxic activity after secondary in vitro
      stimulation in the presence of vS, vM or vN infected L14 cells. The cytotoxic
      activity was induced and directed against the homologous vS and vM infected cells
      but no cytotoxic activity occurred at all against vN infected cells. While vM
      infected cells induced a cytotoxic activity against vM infected cells only, vS
      infected cells stimulated a cross-reactive cytotoxic activity against vM and vN
      infected cells in addition to that against vS infected cells. This latter
      cytotoxicity may be due to an increase in a non-specific background of Natural
      Killer or lymphocyte activated killer activity, which is seen also after
      coculture with wild type vaccinia virus (vW) infected cells. Thus these results
      are of practical importance in two respects. First, lymphoid B cell lines
      represent an excellent tool for determining which viral antigens are recognized
      by cytotoxic lymphocytes and second, they indicate the need to incorporate the M
      and S genes into a TGEV vaccine to induce cellular immunity against TGEV.

PMID- 9779560
TI  - Pharmacokinetics of doxycycline in pigs following oral administration in feed.
AB  - Doxycycline medicated feed was administered to healthy fattening pigs for an 8
      day period either for 1 h every 12 h or ad libitum. The average dosage regimen
      ranged between 11.8 and 13.3 mg/kg/day. Doxycycline concentrations were
      determined in plasma, lung and nasal mucosa using a high performance liquid
      chromatography assay (HPLC). The agreement between the doxycycline HPLC assay and
      a bioassay was also assessed in plasma. Following the multiple medicated feed
      administration every 12 h, the plasma concentrations were best described by a one
      compartmental model with first-order absorption. Steady-state plasma
      concentrations ranged between 0.7 and 1 microgram/mL. The mean accumulation
      factor and elimination half-life were, respectively, 1.8 +/- 0.4 and 5.9 +/- 1.0
      h. Following ad libitum administration of medicated feed, steady-state plasma
      concentrations ranged between 0.9 and 1.5 micrograms/mL. At the end of the
      treatment, the doxycycline lung and nasal mucosa concentrations were 1.7 +/- 0.4
      micrograms/g and 2.9 +/- 0.6 micrograms/g, respectively. These data validate the
      dosage regimen tested in order to control pig respiratory infections, provided
      that controlled clinical studies are confirmatory.

PMID- 9779561
TI  - Assessment of the risk of infestation of pastures by Ixodes ricinus due to their
      phyto-ecological characteristics.
AB  - This study aims to assess the relationships between the phyto-ecological
      characteristics of grazing pastures and their risk of being infested by the hard
      tick Ixodes ricinus. To that purpose, 128 pastures belonging to 20 dairy farms
      were observed from April to July 1994. The farms were located in western France.
      Assessment of the tick population was made by four monthly, blanket-dragging
      sessions. The average infestation rate was 40.2%. Six types of pastures were
      identified according to their basic phyto-ecological characteristics using a
      factorial analysis of correspondences followed by a hierarchical ascending
      classification. These identified types were significantly related to the
      infestation rates, thereby making it possible to provide a predictive value in
      risk assessment. The infestation rates were high (96% on average) in two types of
      pastures characterized by their proximity to woods, and low (13%) in two other
      types characterized by seeded grass species located at some distance from woods,
      and intermediate (39% on average) in the last two types.

PMID- 9779562
TI  - Factor VII and activated factor VII content of prothrombin complex concentrates.

PMID- 9779563
TI  - Hemoglobin determination in blood donors.

PMID- 9779564
TI  - Determination of glycocalicin in platelet concentrate supernatants stored in a
      synthetic medium (Seto solution)

PMID- 9779565
TI  - Membrane adsorptive properties of a new polyurethane leukocyte reduction filter
      in comparison with those of a negatively charged polyester filter.

PMID- 9779567
TI  - Asymptomatic type II mixed cryoglobulinemia with a very high cryocrit level
      secondary to HCV infection.

PMID- 9779566
TI  - Does HCV screening of blood donors affect transmission of hepatitis G virus in
      dialysed patients?

PMID- 9779568
TI  - Relationship between antibodies dependent on calcium chelators and the H antigen.

PMID- 9779569
TI  - Introduction of malaria antibody ELISA.

PMID- 9779570
TI  - The use and quality control of leukocyte-depleted cell concentrates.

PMID- 9779572
TI  - Analyte-receptor binding kinetics for biosensor applications. An analysis of the
      influence of the fractal dimension on the binding rate coefficient.
AB  - The diffusion-limited binding kinetics of antigen (analyte), in solution with
      antibody (receptor) immobilized on a biosensor surface, is analyzed within a
      fractal framework. Most of the data presented is adequately described by a single
      fractal analysis. This was indicated by the regression analysis provided by
      Sigmaplot. A single example of a dual-fractal analysis is also presented. It is
      of interest to note that the binding-rate coefficient (k) and the fractal
      dimension (Df) both exhibit changes in the same and in the reverse direction for
      the antigen-antibody systems analyzed. Binding-rate coefficient expressions, as a
      function of the Df developed for the antigen-antibody binding systems, indicate
      the high sensitivity of the k on the Df when both a single- and a dual-fractal
      analysis are used. For example, for a single-fractal analysis, and for the
      binding of antibody Mab 0.5 beta in solution to gp120 peptide immobilized on a
      BIAcore biosensor, the order of dependence on the Df was 4.0926. For a dual
      fractal analysis, and for the binding of 25-100 ng/mL TRITC-LPS
      (lipopolysaccharide) in solution with polymyxin B immobilized on a fiberoptic
      biosensor, the order of dependence of the binding-rate coefficients, k1 and k2,
      on the fractal dimensions, Df1 and Df2, were 7.6335 and -11.55, respectively. The
      fractional order of dependence of the k(s) on the Df(s) further reinforces the
      fractal nature of the system. The k(s) expressions developed as a function of the
      Df(s) are of particular value, since they provide a means to better control
      biosensor performance, by linking it to the heterogeneity on the surface, and
      further emphasize, in a quantitative sense, the importance of the nature of the
      surface in biosensor performance.

PMID- 9779576
TI  - Optimization of protease immobilization by covalent binding using glutaraldehyde.
AB  - Immobilization of a protease, Flavourzyme, by covalent binding on various
      carriers was investigated. Lewatit R258-K, activated with glutaraldehyde, was
      selected among the tested carriers, because of the highest immobilized enzyme
      activity. The optimization of activation and immobilization conditions was
      performed to obtain high recovery yield. The activity recovery decreased with
      increasing carrier loading over an optimal value, indicating the inactivation of
      enzymes by their reaction with uncoupled aldehyde groups of carriers. The buffer
      concentrations for carrier activation and enzyme immobilization were optimally
      selected as 500 and 50 mM, respectively. With increasing enzyme loading, the
      immobilized enzyme activity increased, but activity recovery decreased.
      Immobilization with a highly concentrated enzyme solution was advantageous for
      both the immobilized enzyme activity and activity recovery. Consequently, the
      optimum enzyme and carrier loadings for the immobilization of Flavourzyme were
      determined as 1.8 mg enzyme/mL and 0.6 g resin/mL, respectively.

PMID- 9779577
TI  - Enzymatic glucuronidation of a novel cholesterol absorption inhibitor, Sch 58235.
AB  - A glucuronide of a novel cholesterol absorption inhibitor was synthesized on a
      200-mg scale in one step via bovine liver glucuronyltransferase-catalyzed
      coupling of the glucuronyl moiety of UDP-glucuronic acid with the phenolic
      hydroxyl of Sch 58235. It was shown that the product yield is limited by the
      hydrolysis of UDP-glucuronic acid by impurities present in the commercial
      microsomal preparation of the transferase. This detrimental effect of UDPGluA
      hydrolysis could be diminished by the presence of high concentration of
      glucuronlytransferase. Optimization of reaction conditions and purification
      procedure resulted in a process that proceeded with 95% conversion and 88%
      isolated product yield. The 13C6-glucuronide of Sch 58235 was prepared with the
      help of a cascade of eight enzymes operating concurrently in one pot.

PMID- 9779578
TI  - Continuous purification of porcine lipase by rotating annular size-exclusion
      chromatography.
AB  - Crude porcine lipase (triacylglycerol lipase, EC 3.1.1.3) was purified in a
      single-stage chromatographic process. The purification was accomplished in a
      batch, as well as in a continuous system. Two types of size-exclusion packing
      materials (Sephadex and Sephacryl) were used. The average x-fold increase in
      purity, and the average recovered activity in the batch Sephadex and Sephacryl
      experiments were 13.6 and 89.7%, and 34.2 and 98.8%, respectively. The average x
      fold increase in purity and the average activity recovered in the continuous
      Sephadex and Sephacryl experiments were 27.1 and 82.5% and 16.2 and 89%,
      respectively. Flow visualization experiments were carried out by tagging the
      protein to be separated with a fluorescent dye. The results from these
      experiments are also reported in this article.

PMID- 9779579
TI  - Isolation and characterization of a newly identified type II restriction
      endonuclease from a local Streptomyces sp. in Taiwan.
AB  - Streptomyces chusanensis ZS-2, isolated from a soil sample in Chusan in Taiwan,
      was found to produce a new Type II restriction endonuclease. This restriction
      enzyme was designated as SchI. The purified enzyme was characterized as having a
      subunit mol wt of 28 kDa, and was apparently free from exonuclease activities. It
      cleaves the phosphodiester bond between the fourth C and the fifth G on the 5'
      CCGCGG-3' sequence of DNAs, leaving a 2-nucleotide protruding end at its 3' site.
      This data suggests that SchI is an isoschizomer of SacII. In addition, based on
      the comparison between SchI and SacII regarding reaction parameters, it seems
      that SchI is a better choice of restriction enzyme for genetic analysis and
      mapping.

PMID- 9779580
TI  - Microbial sensor for new-generation cephalosporins based in a protein-engineered
      beta-lactamase.
AB  - A protein-engineered beta-lactamase, constructed by site-directed mutagenesis in
      Escherichia coli (E104M/G238S), and having broadened specificity, was able to
      degrade cephalosporins of first, second, and third generations. Manipulations of
      culture conditions allowed an increase in beta-lactamase specific activity by up
      to twofold. The resultant bacteria were used to construct an immersable whole
      cell biosensor for the detection of new-generation cephalosporins. Cells were
      immobilized on agar membranes, which in turn were attached to the surface of a
      flat pH electrode, thus constituting a biosensor based on the detection of pH
      changes. The sensor was able to detect second- and third-generation
      cephalosporins: cefamandole (0.4-4 mM), cefotaxime (0.4-3.5 mM), and cefoperazone
      (0.3-1.85 mM). Response times were between 3.5 and 11 min, depending on the kind
      of cephalosporin tested. The biosensor was stable for at least 7 d, time during
      which up to 100 tests were performed.

PMID- 9779581
TI  - Conformation induction in melanotropic peptides by trifluoroethanol: fluorescence
      and circular dichroism study.
AB  - Conformation induction in the two related peptides, alpha-melanocyte stimulating
      hormone (alpha-MSH) and delta-melanocyte stimulating hormone (delta-MSH), have
      been studied in solvent media containing varying percentages of the membrane
      mimetic solvent 2,2,2-trifluoroethanol (TFE) using fluorescence and circular
      dichroism (CD) spectroscopy. Singular value decomposition (SVD) analysis of the
      CD spectra at different TFE concentrations showed that these spectra can be
      described as linear combinations of only two distinct basis spectra,
      corresponding to the peptides in the random-coil and 'folded' conformations. For
      alpha-MSH the spectrum of the folded state is very similar to the standard
      spectrum of the alpha-helix, while that for delta-MSH has partial resemblance to
      the helical spectrum. Fitting the data on ellipticity (at 222 nm) as a function
      of TFE volume fraction to an equation based on a two-state model describing TFE
      induced conformation induction in the peptides gave values of (1.1 +/- 0.4) and
      (4.2 +/- 0.5) kcal mol-1 for alpha-MSH and delta-MSH, respectively, for the free
      energy of equilibrium between the helix and coil forms in water. Measurement of
      fluorescence emission parameters (emission maximum, quantum yield, steady-state
      anisotropy and mean excited-state lifetime) indicated that the microenvironment
      around the single tryptophan residues of both peptides changes in like manner
      with increasing concentration of TFE in the solvent. The similarity of
      fluorescence behaviour of the peptides suggests that their Trp fluorophores do
      not participate in secondary structure formation in TFE.

PMID- 9779582
TI  - Time resolved emissions in the picosecond range of single tryptophan recombinant
      myoglobins reveal the presence of long range heme protein interactions.
AB  - We have analyzed the time resolved fluorescence emission in the subnanosecond
      range of recombinant wild-type SW myoglobin and its single TRP mutants W7F and
      W14F. These recombinants carry a methionine at the N1 terminal end. The emission
      of Trp-7 in the met form of W14F showed residual lifetime components much shorter
      than those estimated after excitation energy transfer to the heme. We propose
      that in this recombinant the N1 methionine is close to Trp-7, thereby producing
      an extra quenching due to either collisions or electron transfer with its sulfur.
      When the measurements were repeated on its CO-form, the extra quenching of Trp-7
      was much decreased, indicating a heme linked conformational change involving the
      amino terminal end of the protein. This hypothesis is supported by ligand linked
      conformational changes in myoglobin, reported by Ansari et al. and by Giardina et
      al. At neutral pH the lifetimes of W7F were consistent with estimations based on
      the atomic coordinates of SW myoglobin. Those of the wild-type were exactly the
      combination of the lifetimes of the two mutants. This suggest that the mutations
      did not affect the overall structure of the protein. However, in the ferric form,
      substitution of Trp-14 in W14F resulted in low stability at acid pH, as evident
      from lifetimes modifications at pH 4.8, while no modifications were produced by
      titrations of W7F to pH 4.5. This suggests a role of Trp-14 in the structural
      stability of myoglobin.

PMID- 9779583
TI  - Base specific complex formation of norfloxacin with DNA.
AB  - We examined the base specificity of the norfloxacin-DNA interaction by measuring
      the binding constant of norfloxacin to various synthetic polynucleotides, using
      the Stern-Volmer and the Benesi-Hildebrand methods. The equilibrium constants
      were largest for poly[d(G-C)2] and poly(dG).poly(dC), suggesting that norfloxacin
      binds preferentially to the G-C bases of calf thymus DNA. We also found that
      norfloxacin has a greater affinity for purine than for pyrimidine. The binding
      mode of norfloxacin to double-stranded polynucleotide was studied using circular
      and linear dichroism (CD and LD). When the norfloxacin was complexed to poly[d(G
      C)2], poly(dG).poly(dC) and DNA, all of the complexes exhibited a similar weak,
      positive CD band and negative LD in the 300-350-nm region. A closer examination
      of the LD spectra suggests that the molecular plane of norfloxacin is near
      perpendicular relative to DNA helix axis that excludes the groove binding mode or
      surface binding of norfloxacin.

PMID- 9779584
TI  - 'Soft-particle' analysis of the electrophoretic mobility of a fibrillated and non
      fibrillated oral streptococcal strain: Streptococcus salivarius.
AB  - The electrophoretic mobility of microbial cell surfaces can be analysed in terms
      of a so-called soft layer model, in which the electrophoretic mobility is
      described as originating from the potentials over the surface charge layer and
      the membrane fixed charges. Often, the polyelectrolyte layer deforms under the
      influence of ionic strength variations. In the soft layer analysis of
      electrophoretic mobilities this is expressed in the softness 1/lambda. Here, we
      determined the softness of two oral streptococcal strains, S. salivarius HB and
      HBC12 from particulate microelectrophoresis in KCl solutions of varying ionic
      strength. Electron microscopy of negatively-stained organisms and X-ray
      photoelectron spectroscopy showed that strain HB had several classes of
      proteinaceous fibrils with lengths up to 178 nm on its outermost surface, while
      variant HBC12 had a bald, peptidoglycan-rich outer surface. The fibrillated
      strain HB appeared as relatively soft (1/lambda equals 1.4 nm) from analysis of
      its electrophoretic mobility, while the bald variant HBC12 was hard (1/lambda
      equals 0.7 nm) due to its comparatively rigid, peptidoglycan-rich outer surface,
      characteristic to Gram-positive bacteria. The presence of proteinaceous fibrils
      on strain HB slightly shielded the membrane fixed charges on HBC12.

PMID- 9779585
TI  - Influence of the level of ceramides in the permeability of stratum corneum lipid
      liposomes caused by sodium dodecyl sulfate.
AB  - The role played by the ceramides in the sublytic interactions of sodium dodecyl
      sulfate (SDS) with liposomes modeling the stratum corneum (SC) lipid composition
      was studied. The surfactant/lipid molar ratios (Re) and the bilayer/aqueous phase
      partition coefficients (k) were determined by monitoring the changes in the
      fluorescence intensity of liposomes due to the 5(6) carboxyfluorescein (CF)
      released from the interior of vesicles. The presence in liposomes of higher and
      lower ceramide proportions than that existing in the SC lipids led to a fall and
      to a rise in the sublytic activity of SDS on these structures. However, the SDS
      partitioning into liposomes (or affinity with these bilayer structures) increased
      as the proportion of Cer increased up to achieve almost a constant value for a
      Cer proportion similar to that in the SC lipids (about 40%). Thus, at low Cer
      proportions the ability of SDS molecules to alter these bilayer structures was
      higher than that for liposomes approximating the SC lipid composition despite
      their reduced partitioning into liposomes. These findings are in agreement with
      the recently reported dependencies of the level of ceramides in skin lipids and
      function barrier abnormalities and could explain in part these dependencies. The
      fact that the free surfactant concentration needed to achieve the two interaction
      levels investigated was lower than the surfactant critical micellar concentration
      (CMC) indicates that permeability alterations were mainly ruled by the action of
      surfactant monomers, regardless of the liposome lipid composition.

PMID- 9779586
TI  - Sterol synthesis. Synthesis of 3 beta-hydroxy-25,26,26,26,27,27,27
      heptafluorocholest-5-en-7-one and its effects on HMG-CoA reductase activity in
      Chinese hamster ovary cells, on ACAT activity in rat jejunal microsomes, and
      serum cholesterol levels in rats.
AB  - 3 beta-Hydroxycholest-5-en-7-one (I; 7-ketocholesterol) is an oxysterol of
      continuing interest in biology and medicine. In the present study, we have
      prepared a side-chain fluorinated analog, 3 beta-hydroxy-25,26,26,26,27,27,27
      heptafluorocholest-5-en-7-one (VI), with the anticipation that the F7
      substitution would block major metabolism of the 7-ketosterol, and thereby
      enhance its potential in vivo effects on serum cholesterol levels and other
      parameters. Chromium trioxide/dimethyl pyrazole oxidation of the acetate
      derivative of the previously described 25,26,26,26,27,27,27-heptafluorocholest-5
      en-3 beta-ol (Swaminathan et al., 1993. J. Lipid Res. 34, 1805-1823) followed by
      mild alkaline hydrolysis gave VI. The effects of VI on 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase activity in Chinese hamster ovary (CHO-K1) cells,
      on acyl coenzyme A-cholesterol acyltransferase (ACAT) activity in rat jejunal
      microsomes, and on serum cholesterol levels and other parameters in male Sprague
      Dawley rats were determined and compared with those obtained with I and with
      another alpha, beta-unsaturated ketosterol, i.e. 3 beta-hydroxy-5 alpha-cholest
      8(14)-en-15-one (II). I and VI showed essentially the same potency, considerably
      less than that of II, in lowering the levels of HMG-CoA reductase activity in CHO
      K1 cells. Whereas addition of II to rat jejunal microsomes inhibited ACAT
      activity (IC50 approximately 3 microM), I and VI had no effect under the
      conditions studied (from 1 to 16 microM). Dietary administration of I, at levels
      of 0.1 and 0.15%, had no effect on food consumption, gain in body weight, or
      serum cholesterol levels. At 0.2%, I caused a modest decrease in body weight gain
      and a slight decrease in serum cholesterol levels (relative to ad libitum but not
      pair-fed control animals). The F7-7-ketosterol VI, at 0.26% in diet (the molar
      equivalent of 0.2% I), had no effect on food consumption, body weight, or serum
      cholesterol levels. Administration of I (0.1, 0.15 or 0.2% in diet) caused
      increases in the weight of small intestine. In contrast, no effect of VI (0.26%
      in diet) on small intestinal weight was observed.

PMID- 9779587
TI  - Interaction between sulfogalactosylceramide and dimyristoylphosphatidylcholine
      increases the orientational fluctuation of their lipid hydrocarbon chains.
AB  - The objective of this study was to investigate the interaction between
      sulfogalactosylceramide (SGC) and dimyristoylphosphatidylcholine (DMPC) in a
      mixed model liposomal system (molar ratio SGC:DMPC, 2:3). Structural and dynamic
      changes of the liposome components were monitored by Fourier-transform infrared
      spectroscopy (FTIR). Thermotropic FTIR analysis of the mixed liposomes showed a
      single gel/liquid crystalline phase transition, centered at approximately 42
      degrees C. Spectral changes of the amide and ester C = O bands arising from
      functional groups at the interfacial region indicated a reduced hydrogen bonding
      of these groups in the mixed liposomes. Pressure-tuning FTIR of mixed liposomes
      showed that the methylene chains of SGC and DMPC were more orientationally
      disordered than those of the individual lipid SGC liposomes or DMPC liposomes.
      These results suggest that the mixed liposomes (molar ratio SGC:DMPC, 2:3)
      consisted of a homogeneous mixture of SGC and DMPC molecules in which mutual
      shielding reduced hydrogen bonding in the interfacial region, with a concurrent
      increase in the orientational disorder of the hydrocarbon chains of both SGC and
      DMPC.

PMID- 9779588
TI  - Amplification of telomeric DNA and the extent of karyotypic evolution.
AB  - The distribution of telomeric DNA in the genomes of the antelope ground squirrel,
      Ammospermophilus harrisii (family Sciuridae; 2n = 32) and the African black
      footed cat, Felis nigripes (family Felidae; 2n = 38) were compared by
      fluorescence in situ hybridization (FISH) technique. These two mammalian species
      have the highest and the lowest amount of C-banded regions, respectively. FISH
      preparations with the human telomeric DNA probe showed that all C-banded segments
      in the A. harrisii chromosomes, except a few intercalary segments, were
      hybridizing with this DNA. F. nigripes showed hybridization only on the termini
      of each chromosome, and the C-banded regions did not hybridize with telomeric DNA
      on FISH analysis. The C-banded chromosomal arms in another rodent species,
      Peromyscus eremicus (family Cricetidae; 2n = 48), when hybridized with human
      telomeric DNA showed signals only in the termini of chromosomes but not in the
      heterochromatic arms. These observations indicate that not all C-banded regions
      in rodent species are telomeric DNA. The amplification of telomeric DNA in
      relation to speciation is discussed.

PMID- 9779589
TI  - Effect of polycyclic aromatic hydrocarbons on somatic chromosomes of coal tar
      workers.
AB  - The genotoxic effect of polycyclic aromatic hydrocarbons (PAHs) on somatic human
      chromosomes obtained from lymphocytes of 49 coal tar workers exposed to 26
      micrograms/m3 benzo(a)pyrene, 16 mg/m3 benzene and 0.04 mg/m3 H2S in the ambient
      air, compared to equal numbers of matched controls breathing air containing 1
      microgram/m3 benzo(a)pyrene, 1.5 mg/m3 benzene and 0.02 mg/m3 H2S, was
      investigated. The mitotic index (MI), chromosome aberrations (CAs), sister
      chromatid exchanges (SCEs) and satellite associations (SAs) were analysed. All
      the parameters showed a significant increase (p < 0.01 and 0.05) in the exposed
      individuals compared with the controls: viz MI, 4.59-7.92; CAs, 0.77-3.0; SCEs,
      5.89-6.80; and SAs, 8.18-14.26. The occurrence of the DG type of satellite
      associations were highest and the 3D type lowest. The frequency of SCEs was
      highest in coal tar workers with an exposure period of 6-10 years. It is
      suggested that these results show PAH is genotoxic for humans.

PMID- 9779590
TI  - Partial purification and characterisation of sugarcane neutral invertase.
AB  - Sugarcane neutral invertase (SNI) has been partially purified from mature
      sugarcane stem tissue to remove any potential competing activity. The enzyme is
      non-glycosylated and exhibits catalytic activity as a monomer, dimer and
      tetramer, most of the activity elutes as a monomer of native M(r) ca 60 k. The
      enzyme displays typical hyperbolic saturation kinetics for Suc hydrolysis. It has
      a K(m) of 9.8 mM for Suc and a pH optimum of 7.2. An Arrhenius plot shows the
      energy of activation of the enzyme for Suc to be 62.5 kJ mol-1 below 30 degrees
      and -11.6 kJ mol-1 above 30 degrees. SNI is inhibited by its products, with Fru
      being a more effective inhibitor than Glc. SNI is significantly inhibited by
      HgCl2, AgNO3, ZnCl2, CuSO4 and CoCl2 but not by CaCl2, MgCl2 or MnCl2. SNI showed
      no significant hydrolysis of cellobiose or trehalose.

PMID- 9779591
TI  - Amylases synthesis in scutellum and aleurone layer of maize seeds.
AB  - The endosperm of germinating maize seeds contains four isozymes of alpha-amylases
      (alpha-amylase-1 to -4) and one isozyme of beta-amylase. The alpha-amylases were
      purified by affinity chromatography on amylose and separated by DEAE-cellulose
      chromatography, into two groups, namely alpha-amylases-1,2 and alpha-amylases
      3,4; and beta-amylase was purified by precipitation as a glycogen-enzyme complex.
      The molecular weight of alpha-amylases-1 and -2 was 46 kD, alpha-amylases-3 was
      44.5 kD and of alpha-amylases-4 was 47.5 kD. The molecular weight of beta-amylase
      was 56 kD. During seed germination increase in amylolytic activity in endosperm
      was mainly contributed by secretion of alpha-amylases from adjoining aleurone
      layer and scutellum. The synthesis and secretion of alpha-amylases was first
      initiated in the scutellum followed by aleurone layers. Exogeneous Ca2+
      stimulated synthesis of alpha-amylases in both eleurone layer and scutellum. In
      contrast, though scutellum and aleurone layer synthesized beta-amylase but it was
      not secreted to the medium. These results suggest that during the early
      germination period, alpha-amylases secreted from scutellum mobilizes starch.

PMID- 9779592
TI  - Purification and characterization of a mannose/glucose-specific lectin from
      Castanea crenata.
AB  - A hemagglutinin was purified from the cotyledons of Japanese chestnut (Castanea
      crenata Sieb. et Zucc.) by affinity chromatography on asialo-fetuin Sepharose 4B
      column followed by anion-exchange and gel permeation chromatography. The
      hemagglutinating activity of Castenea crenate agglutinin (CCA) was strong for
      sialidase-treated human erythrocytes, but was inhibited by mannose, glucose, and
      their derivatives as well as by glycoproteins having an N-linked complex
      carbohydrate type. The apparent M(r) of intact CCA was determined to be ca
      257,000 by gel filtration using a Superose 12 column. In SDS-PAGE, under reducing
      and non-reducing conditions, CCA migrated as a single band of M(r) 37,000.
      Therefore, the intact CCA may be composed of six or eight identical subunits
      without disulfide bonds. In addition, CCA showed strong mitogenic activity
      similar to other lectins. The N-terminal amino acid of CCA may be blocked since
      no amino acid was detected by direct sequence analysis. Amino acid analysis
      showed that CCA was rich in glycine, but did not contain cysteine residues. Some
      properties of CCA were similar to mannose/glucose-specific legume lectins, but
      our data suggest that the molecular structure of CCA is different.

PMID- 9779594
TI  - Rhamnogalacturonan II from cell walls of Cryptomeria japonica.
AB  - The pectic polysaccharides isolated from cell walls of xylem-differentiating
      zones of sugi (Cryptomeria japononica) were degraded with endo-alpha-(1-->4)
      polygalacturonase and the polysaccharides, composed mainly of rhamnogalacturonan
      II (RG-II), were obtained from the degradation products. These polysaccharides
      consisted of rhamnosyl, fucosyl, arabinosyl, xylosyl, galactosyl, glucosyl,
      galacturonic acid, glucuronic acid and the characteristic sugars of RG-II,
      namely, 2-O-methylfucose, 2-O-methylxylose, apiose, aceric acid and
      thiobarbituric acid assay-positive glycosyl ?probably, 3-deoxy-D-manno-2
      octulosonic acid (Kdo) and 3-deoxy-D-lyxo-heptulosaric acid (Dha)?. The
      polysaccharides contained the glycosyl residues of RG-II, besides small amounts
      of the glycosyl linkages of RG-I. The RG-II was structurally analysed by partial
      acid hydrolysis and lithium treatment in ethylenediamine. The glycosyl sequences
      of three compounds generated by partial hydrolysis were not identical to the
      partial structure of the sycamore (Acer pseudoplatanus) RG-I and RG-II structures
      previously proposed by Albersheim et al. Furthermore, five novel glycosyl
      sequences were detected in the products from lithium treatment. The results
      suggest that the structure of sugi RG-II is somewhat different from that of
      sycamore RG-II.

PMID- 9779593
TI  - Purification and characterization of a lectin from seeds of Vatairea macrocarpa
      Duke.
AB  - A lectin from Vatairea macrocarpa Duke seeds (VML) was isolated using affinity
      chromatography on a guar gum column. The lectin, a glycoprotein without
      erythrocyte specificity, displays specificity to galactose and some derivatives.
      On SDS-polyacrylamide gels, V. macrocarpa seed lectin is composed of two major
      high-Mr bands of 34 and 32 kDa and two minor low-Mr bands of 22 and 13 kDa. N
      Terminal sequencing showed that the 34, 32, and 13 kDa products possess identical
      N-terminal sequence, which display best similarity with the N-terminal portion of
      Robinia pseudoacacia lectins (RPL). On the other hand, the N-terminal sequence of
      the 22 kDa band can be aligned with an internal sequence of RPL starting at
      residue 149 of the cDNA-derived sequence. These data indicate that, like other
      leguminous lectins, VML is made up of a mixture of one-chain 30-35 kDa glycoforms
      and of 22 and 13 kDa endogenous C- and N-terminal fragments. Size-exclusion
      chromatography indicated that, at neutral pH, VML is predominantly a dimeric (70
      kDa) protein, although tetramers (115 kDa) and larger aggregates (300 kDa) were
      also present.

PMID- 9779595
TI  - Mono-tetrahydrofuran acetogenins from Goniothalamus giganteus.
AB  - Goniotetracin and a mixture of (2,4-cis and trans)-gonioneninone, new, bioactive,
      mono-tetrahydrofuran (THF) gamma-lactone and ketolactone acetogenins, were
      isolated from the bark of Goniothalamus giganteus (Annonaceae) by activity
      directed fractionation using the brine shrimp lethality test (BST). The
      structures were elucidated based on spectroscopic and chemical methods. Their
      absolute stereochemistries were determined by the advanced Mosher ester method.
      Both showed selective and significant cytotoxicities, comparable to the potency
      of adriamycin, to the human pancreatic tumour cell line (PACA-2), while
      goniotetracin and goniothalamicin were comparable to the activity of rotenone
      against yellow fever mosquito larvae.

PMID- 9779596
TI  - Linear acetogenins from Goniothalamus donnaiensis.
AB  - Four linear acetogenins, donhepocin (1), 34-epi-donhepocin (1'), donhexocin and
      donbutocin, have been isolated from the roots of Goniothalamus donnaiensis. 1 and
      1', isolated as an epimeric pair, contain a rare gamma-hydroxymethyl-gamma
      lactone. Their structures have been established on the basis of spectral and
      chemical evidence.

PMID- 9779598
TI  - Contribution of muscle proteinases to meat tenderization.
AB  - The exact mechanisms involved in the postmortem meat tenderization process and
      the nature of changes associated with improvement in tenderness are complex and
      not fully understood. Based on the relevant evidence thus far obtained, the focus
      of this review is on clarifying the factors affecting meat tenderness,
      particularly the toughening and tenderness phases, possible endogenous
      proteinases involved in meat tenderization and how these proteinases contribute
      to meat tenderization. Of the different biochemical and ultrastructural changes
      occurring in the meat tenderization process, myofibril disruption at the Z-disk
      and contractile proteins are discussed in detail. This myofibril disruption can
      perhaps be ascribed to the synergistic action of calcium-dependent proteinases
      (both mu- and m-calpains) and lysosomal proteinases, especially the cathepsins B
      and L.

PMID- 9779597
TI  - Steroidal alkaloid glycosides from Solanum orbignianum.
AB  - Aerial parts of Solanum orbignianum afforded a new steroidal alkaloid glycoside,
      leptinidine 3-O-beta-D-glucopyranoside, together with the known alkaloids
      leptinidine, leptinine I and leptinine II. Their structures were established by
      spectroscopic methods.

PMID- 9779599
TI  - Studies on fetal hemoglobin and gamma globin gene triplication in newborns in
      Jordan.
AB  - Quantitation of fetal hemoglobin (Hb F) and quantitation of it's gamma chain
      composition is important for the identification of different hemoglobinopathies.
      This is the first study done on the Jordanian newborns to test the hematological
      data and the gamma globin chain variants. A total of 52 randomly selected healthy
      Jordanian newborns were examined. The quantitation of the G gamma and A gamma
      chains combined with gene mapping using XmnI digestion, were used in the
      identification of one case of G gamma triplication among the studied samples. A
      family study of this case showed that adults carrying one copy of this G gamma
      triplication (13Kb XmnI fragment) had normal levels of HbF (< 1%) and high levels
      of G gamma (> 80%) while no homozygotes were detected. The remaining 51 newborns
      had normal frequency values of G gamma and A gamma chains. The frequency of the A
      gamma T chain among the 52 samples was 0.22. No abnormal alpha or beta chain
      variants were detected except for one case of HbS.

PMID- 9779600
TI  - p53 gene alternation in squamous cell carcinoma of the esophagus detected by PCR
      cold SSCP analysis.
AB  - Mutations of the p53 tumor suppressor gene play an important role in the
      development of common human malignancies. Previous reports revealed that the
      frequencies of p53 alternations in esophageal carcinoma varied from 26% to 87%.
      The clinical significance of p53 alternations is still disputed. In the present
      study, we used polymerase chain reaction--"cold" single-strand conformation
      polymorphism (PCR-"cold" SSCP)--to investigate p53 genetic alternations in 63
      surgical specimens of esophageal squamous cell carcinoma (ESC). Our experiments
      showed that the optimum buffer temperature for "cold" SSCP analysis was 14
      degrees C while the PCR products were around 200-300 bp in size. Among 63
      tumorous samples, p53 alternations was detected in 47 tumors, or an incidence
      rate of 74.6%. For nontumorous mucosal samples, the incidence of p53 alternations
      was 55.5% (35/63 samples). Additionally, p53 alternations occurred most
      frequently at exon 6 (50.8%), followed by exon 7 (33.3%), exon 8 (17.5%) and exon
      5 (12.7%). Multiple genetic alternations (> or = 2 exons) between p53 exons 5-8
      in the same examined samples were found in 21 (33.3%) of 63 tumors, and in 8
      (12.7%) of 63 nontumorous mucosal specimens. Our results further showed that p53
      alternations did not correlate with age, depth of tumor invasion, lymph node
      metastasis, tumor stage, cell differentiation or lymphovascular invasion in ESC
      (P > 0.05). Moreover, the survival rate in patients with p53 alternations was
      similar to that in patients without p53 alternations (P > 0.05). In conclusion,
      PCR-"cold" SSCP is a rapid and sensitive method for identifying p53 genetic
      alternations. p53 genetic alternations occur with a relatively high incidence for
      ESC, but p53 abnormality has no impact on prognosis.

PMID- 9779601
TI  - The effect of sphenopalatine postganglionic neurotomy on the alteration of local
      cerebral blood flow of normotensive and hypertensive rats in acute cold stress.
AB  - The cold season of a year has been reported to have the highest incidence of
      strokes. Present studies were designed to test whether the parasympathetic
      denervation plays any role in the regulation of local cerebral blood flow (LCBF)
      in anesthetized animals exposed to a cold environment. Each species of Wistar
      Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) was divided into four
      groups: sphenopalatine postganglionic neurotomy (SPNx) or a control group at room
      temperature (20 degrees C) or in a cold environment (5 degrees C), respectively.
      LCBF in 14 brain structures was measured using the [14C] iodoantipyrine technique
      and tissue dissecting methods. Our results show that SPNx did not significantly
      alter physiological parameters and LCBF in WKY and SHR kept at either 20 degrees
      C or 5 degrees C. However, 30 minutes of cold exposure caused a significant
      decrease in the core body temperature of both the WKY and SHR groups (P < 0.05,
      Student's paired t-test) and a significant decrease in LCBF in 3 of 14 brain
      areas: the temporal cortex (TC), inferior colliculus (IC) and vermis (VER) of
      both WKY and SHR (P < 0.05, MANOVA). The percentages of decrease were 24% (TC),
      12% (IC), 12% (VER) and 19% (TC), 16% (IC), 15% (VER), respectively. Our findings
      indicate that in a cold environment, the lower LCBFs in some areas of the brain
      may be related to decreased body temperature. Whether they are related to the
      higher prevalence of stroke in winter needs further investigation.

PMID- 9779602
TI  - Detection of endogenous digitalis-like immunoreactive factors in human blood.
AB  - Digitalis-like immunoreactive factors (DLIF) are special types of steroids with
      lactone rings in their structures. Clinically, this type of compound can be used
      as medicine for heart failure; thus, the elevated endogenous DLIF found under
      certain pathological conditions are interferent substances in digoxin
      immunoassay. Endogenous DLIF with biological and immunological properties similar
      to cardiotonic drugs, such as digoxin, have been found in several tissues and
      body fluids of animals and humans. Since these endogenous Na+, K(+)-ATPase
      inhibitors can be considered hormones in nature, immunoassays must be selected
      detection of them to achieve the required sensitivity and specificity. In this
      study, we used three sets of in-house formulated immunoassays for DLIF and
      ouabain-like factors (OLF) detection. Using a polyclonal antibody-based ouabain
      enzyme immunoassay, the mean +/- S.E.M. of OLF in the sera of 10 healthy
      individuals were determined to be (9.1 +/- 0.9) x 10(-11) M. Using a monoclonal
      antibody-based ouabain enzyme immunoassay, the mean +/- S.E.M of OLF in the sera
      of 10 healthy individuals was (8.2 +/- 1.2) x 10(-11) M while using a antibody
      fragment Fab-based enzyme immunoassay for digoxin, the mean +/- S.E.M of DLIF in
      11 healthy individuals was (4.0 +/- 1.2) x 10(-10) M. In conclusion, our
      immunological data indicate that DLIFs are normal constituents of human blood.
      Although DLIF is the major component, coexistence of OLF with DLIF in healthy
      individuals can not be excluded.

PMID- 9779603
TI  - Screening of yeasts from Brazilian Amazon rain forest for extracellular
      proteinases production.
AB  - Eighty seven yeast strains representing 34 species isolated from Parahancornia
      amapa fruit and associated Drosophila flies collected in the Brazilian Amazon
      rain forest, were screened for proteinase production. Proteolytic activity was
      tested through casein hydrolysis in solid medium supplemented with 0.5% casein
      and glucose. Among 23 strains, 18 from genus Candida and 5 from Pichia were
      caseinolytic and produced proteinases in yeast carbon base liquid medium
      supplemented with casein 0.01%. The proteolytic activity was tested on pH ranging
      from 2.0 to 9.0 in correspondence to the pH of the cultures media in which the
      yeasts were grown. Six highly proteolytic strains: Candida parapsilosis AP153A,
      C. krusei AP176, C. sorbosa DR215, C. sorbosa AP259, C. valida AP209A and C.
      sorboxylosa AP287 were selected and the pH optima of production and the
      proteolytic activity were determined. In general the secretion of proteinase was
      maximum throughout the exponential and the stationary phases. Greater production
      occurred in acidic culture and high activity was observed at pH 3.0, 4.0 and 5.0.

PMID- 9779604
TI  - Lactobacillus amylolyticus sp. nov., isolated from beer malt and beer wort.
AB  - Some of the strains used for the biological acidification in breweries belong to
      L. delbrueckii subsp. delbrueckii, L. delbrueckii subsp. lactis or L. fermentum.
      However, more recent studies showed that most strains isolated are
      physiologically different from the above mentioned species and were tentatively
      allocated to Lactobacillus amylovorus. Genotypic studies of 25 strains
      exclusively isolated from beer malts and beer worts, showed, that there were
      differences to the type strain of L. amylovorus concerning DNA-DNA similarities
      and the sequences of their 16S and 23S rRNA genes. Therefore, we propose to
      combine these strains in a new species of the genus Lactobacillus, namely L.
      amylolyticus. Strain DSM 11664 is proposed as the type strain. An rRNA targeted
      oligonucleotide probe was designed that allows a fast and reliable identification
      of Lactobacillus amylolyticus.

PMID- 9779606
TI  - A DNA probe for the detection and identification of Bacillus sporothermodurans
      using the 16S-23S rDNA spacer region and phylogenetic analysis of some field
      isolates of Bacillus which form highly heat resistant spores.
AB  - The spacer regions between the 16S and 23S rRNA genes (spacer regions 1) of
      Bacillus sporothermodurans were PCR-amplified, cloned and sequenced. Six unique
      spacer sequences in four size classes were recovered from two strains, rrnA
      (about 190 bp), rrnB (about 303 bp), rrnC (355 bp) and rrnD (554 bp). rrnD
      contained two tRNA genes which were deciphered as tRNA(ala) and tRNA(ile)
      separated from each other by 13 nucleotides. The primary structures of the tRNA
      molecules clearly resembled those found in Bacillus subtilis; the tRNA(ala) genes
      were identical and the tRNA(ile) genes were 95% similar. The mixed rrnA and rrnB
      spacers when PCR-amplified from chromosomal DNA were effective as a hybridization
      probe for identification of B. sporothermodurans strains. However, high
      background signals with DNA from some other bacilli were encountered. A more
      discriminating probe was prepared from the cloned rrnB spacer region. Of eight
      aerobic, endospore-forming bacteria isolated from silage following heat
      enrichment, one was identified as B. sporothermodurans using the probe and its
      identity was confirmed from partial 16S rDNA analysis (phylotyping). This
      indicated that contamination in milk and dairies by B. sporothermodurans could
      originate from cattle feeds such as silage. Of the other seven silage strains,
      only two were identified conclusively by phylotyping and three represented
      probable new species. The latter three strains were subjected to phylogenetic
      analysis using almost complete 16S rDNA sequences. Branch lengths, bootstrap
      percentage values, and 16S rDNA similarity to other Bacillus species suggested
      that these isolates are likely to constitute new species within the genus
      Bacillus.

PMID- 9779605
TI  - Phylogenetic position of phytopathogens within the Enterobacteriaceae.
AB  - The almost complete 16S rDNA sequences of twenty nine plant-associated strains,
      representing species of the genera Erwinia, Pantoea and Enterobacter were
      determined and compared with those of other members of the Enterobacteriaceae.
      The species of the genus Erwinia may be divided into three phylogenetic groups.
      Cluster I represents the true erwinias and comprises E. amylovora, E.
      mallotivora, E. persicinus, E. psidii, E. rhapontici and E. tracheiphila. We
      propose to unite the species of cluster II, E. carotovora subsp. atroseptica, E.
      carotovora subsp. betavasculorum, E. carotovora subsp. carotovora, E. carotovora
      subsp. odorifera, E. carotovora subsp. wasabiae, E. cacticida, E. chrysanthemi
      and E. cypripedii in the genus Pectobacterium respectively as P. carotovorum
      subsp. atrosepticum comb. nov., P. carotovorum subsp. betavasculorum comb. nov.,
      P. carotovorum subsp. carotovorum comb. nov., P. carotovorum subsp. odoriferum
      comb. nov., P. carotovorum subsp. wasabiae comb. nov., P. cacticidum comb. nov.,
      P. chrysanthemi and P. cypripedii. The species E. alni, E. nigrifluens, E.
      paradisiaca, E. quercina, E. rubrifaciens and E. salicis, comprising cluster III,
      are being classified into a new genus Brenneria gen. nov. respectively as B. alni
      comb. nov., B. nigrifluens comb. nov., B. paradisiaca comb. nov., B. quercina
      comb. nov., B. rubrifaciens comb. nov. and B. salicis comb. nov. The species of
      the genus Pantoea, included in this study, form a monophyletic unit (cluster IV),
      closely related with Erwinia, whereas the three phytopathogenic species of the
      genus Enterobacter are scattered among the genera Citrobacter and Klebsiella.

PMID- 9779607
TI  - Differentiation of Actinobacillus pleuropneumoniae strains by sequence analysis
      of 16S rDNA and ribosomal intergenic regions, and development of a species
      specific oligonucleotide for in situ detection.
AB  - The aims of this study were to characterize and determine intraspecies and
      interspecies relatedness of Actinobacillus pleuropneumoniae to Actinobacillus
      lignieresii and Actinobacillus suis by sequence analysis of the ribosomal operon
      and to find a species-specific area for in situ detection of A. pleuropneumoniae.
      Amplification and sequence analysis of the 16S-23S rDNA ribosomal intergenic
      sequence (RIS) from the three species showed the existence of two RIS's,
      differing by about 100 bp. Both sequences contained a region resembling the
      ribonuclease III cleavage site found in Escherichia coli. The smaller RIS
      contained a Glu-tRNA gene, and the larger one contained genes encoding Ile-tRNA
      and Ala-tRNA. These tRNA's showed a high sequence homology to the respective tRNA
      genes found in E. coli. Sequence analysis of the RIS's showed a high degree of
      genetic similarity of 24 strains of A. pleuropneumoniae. The larger RIS's were
      different between the 3 species tested. The sequence of the 16S ribosomal gene
      was determined for 8 serotypes of A. pleuropneumoniae. These sequences showed
      only minor base differences, indicating a close genetic relatedness of these
      serotypes within the species. An oligonucleotide DNA probe designed from the 16S
      rRNA gene sequence of A. pleuropneumoniae was specific for all strains of the
      target species and did not cross react with A. lignieresii, the closest known
      relative of A. pleuropneumoniae. This species-specific DNA probe labeled with
      fluorescein was used for in situ hybridization experiments to detect A.
      pleuropneumoniae in biopsies of diseased porcine lungs.

PMID- 9779608
TI  - Killer activity of Tilletiopsis albescens Gokhale: taxonomic and phylogenetic
      implication.
AB  - Killer activity expressed at pH values ranging from 3.5 to 8.0 was found in the
      Tilletiopsis albescens VKM-2822. Its killer phenotype was cureless. The toxin
      excreted with a molecular mass above 10 kDa is fungicidal, thermolabile,
      sensitive to proteinase K and was specified as a mycocin. The latter does not act
      against ascomycetous, sporidiobolaceous and tremellaceous yeasts. In contrast to
      all other Rhodotorula species, Rh. bacarum, Rh. hinnulea and Rh. phylloplana are
      sensitive to the mycocin studied. Also, its killing pattern includes the species
      of the genera Exobasidium, Farysia, Protomyces, Pseudozyma, Sporisorium, Taphrina
      and Ustilago. The host range of T. albescens mycocin is discussed from taxonomic
      and phylogenetic viewpoints.

PMID- 9779609
TI  - The use of biologically produced ferrihydrite for the isolation of novel iron
      reducing bacteria.
AB  - Ferric iron was produced anaerobically from ferrous iron through the metabolic
      activity of recently described ferrous iron-oxidizing, nitrate-reducing bacteria.
      It was identified as poorly crystallized 2-line ferrihydrite with a particle size
      of 1-2 nm. This biologically produced ferrihydrite was shown to be a suitable
      electron acceptor for dissimilatory ferric iron-reducing bacteria in freshwater
      enrichment cultures, and was completely reduced to the ferrous state; no
      magnetite formation occurred. Geobacter metallireducens was also able to
      completely reduce the biologically produced ferrihydrite. These results indicate
      the possibility of an anaerobic, microbial cycling of iron. Using the
      biologically produced ferric iron, two isolates of obligately anaerobic,
      dissimilatory ferric iron-reducing bacteria, strains Dfr1 and Dfr2, were obtained
      from freshwater enrichment cultures. Analysis of 16S rRNA gene sequences revealed
      an affiliation with the Geobacter cluster within the family Geobacteraceae. The
      sequence similarity between strains Dfr1 and Dfr2 is 92.5%. The closest relative
      of strain Dfr1 is Geobacter sulfurreducens with 92.9%, and of strain Dfr2
      Geobacter chapelleii with 93.7% sequence similarity. In addition, strains Dfr1
      and Dfr2 are both able to grow by dissimilatory reduction of Mn(IV), S degree,
      and fumarate. Furthermore, strain Dfr2 is able to reduce akaganeite (beta-FeOOH),
      a more crystallized type of ferric iron oxide.

PMID- 9779610
TI  - Application of 23S rDNA-targeted oligonucleotide probes specific for enterococci
      to water hygiene control.
AB  - Identification of enterococci species by hybridization with recently designed
      species-specific and group-specific 23S rDNA-targeted oligonucleotide probes was
      superior to results obtained with a common biochemical test panel. Considering
      these findings, a molecular biological procedure for the detection of enterococci
      in water samples was developed. A short enrichment is followed by an
      amplification step and a hybridization reaction in microtiter plate format. The
      detection limit is about 1 CFU/ml, and results are available within 26 h.

PMID- 9779612
TI  - Reverse-transcription polymerase chain reaction for the detection of viruses from
      plants and aphids.
AB  - A reverse transcription polymerase chain reaction (RT-PCR) protocol used for the
      detection of potato viruses in dormant tubers and leaves and in an aphid vector
      is described. Problems in plant sample preparation from different hosts, uneven
      distribution or low concentration of viruses and the presence of PCR inhibitors
      in plant extracts are discussed and various ways to eliminate their effect are
      described. Using Potyviridae viruses, it has been shown that RT-PCR in various
      modified forms can be used to differentiate viruses at the level of family,
      genus, species, strains and their subtypes or serotypes. The specificity of
      primer pairs and PCR modifications has been used to separate closely related
      potato viruses A and PVY strains (PVY(O), PVY(N) and PVY(NTN)) from a known
      mixture.

PMID- 9779613
TI  - Critical level and detection limit: performance measures for PCR-based assays.
AB  - In clinical diagnostic work, sensitivity and specificity are key assay features.
      In this note we introduce two clinically relevant statistical assay performance
      measures, the critical level (CL), and the detection limit (DL) for the PCR-based
      assay. To allow for easy access to these characteristics a Windows-based program
      has been developed. The application of CL and DL by means of examples is
      described.

PMID- 9779614
TI  - Rapid isolation of both double-stranded RNA and PCR-suitable DNA from the
      obligate biotrophic phytopathogenic fungus Uncinula necator using a commercially
      available reagent.
AB  - A method for rapid extraction of both double-stranded RNA (dsRNA) and DNA from an
      obligate biotrophic phytopathogenic fungus is described. Lyophilised fungal
      material is incubated in a commercial guanidium thiocyanate reagent. Proteins and
      cell debris are centrifuged by chloroform precipitation. After precipitation in
      isopropanol and washing in 75% ethanol, nucleic acids are resuspended in water
      (10 microl/mg fungal dry weight). DsRNA is directly visualised by agarose gel
      electrophoresis. DNA contained in 10-fold dilutions of the samples proved to be
      suitable for PCR-based experiments.

PMID- 9779615
TI  - Clinical evaluation and applications of the Amplicor HBV Monitor test, a
      quantitative HBV DNA PCR assay.
AB  - Viral load has emerged recently as a reliable marker of disease progression and
      therapeutic efficacy in chronic infections, including AIDS and hepatitis C. The
      clinical management of type B hepatitis could also be improved by monitoring
      viremia levels in patients with chronic liver disease undergoing anti-viral
      treatment. To address this question we evaluated the performance of a newly
      developed, quantitative PCR assay (Amplicor HBV Monitor test, Roche Diagnostic
      Systems) in the assessment of viremia changes over time in a group of 45 patients
      with chronic active hepatitis (CAH) who received interferon treatment. Of the 45
      patients, 14 were HBsAg and anti-HBeAg positive and 31 HBsAg, HBeAg positive.
      Follow-up extended up to 24 months. An average of ten samples per patient were
      analyzed for levels of ALT, IgM anti-HBc (Abbott Laboratories), HBV DNA by in
      house dot-blot hybridization and hybridization-capture assays (HBV-DNA hybrid
      capture kit, Murex Diagnostics) and by Amplicor HBV Monitor. A sustained
      biochemical response was observed at the end of treatment in 12 HBeAg-positive
      and in seven anti-HBeAg positive patients. This was accompanied by the
      disappearance of HBeAg and of HBV DNA (hybridization assays) in all cases and by
      the clearance of IgM anti-HBc in 70% of the cases. Viremia (quantitative PCR
      assay) became undetectable only in 25-30% of cases and was associated with the
      loss of HBsAg. A good correlation was observed between the time course of IgM
      anti-HBc, quantitative PCR and dot-blot hybridization although the latter missed
      33% of viremic samples. Together, these results indicate that the Amplicor HBV
      Monitor test is a robust and standardized assay for quantifying HBV viremia
      levels in the range from 10(2) to 10(7) copies/ml. Compared to other current
      markers, viral load may provide additional clinical information by predicting
      long term virologic response and HBsAg clearance in patients with normal ALT at
      the end of interferon therapy.

PMID- 9779616
TI  - Development of a multiplex immunocapture RT-PCR assay for detection and
      differentiation of tomato and tobacco mosaic tobamoviruses.
AB  - Immunocapture (IC) RT-PCR assays were developed for detection of tomato (ToMV)
      and tobacco mosaic (TMV) tobamoviruses in spruce and pine extracts. When purified
      viruses were diluted in root or needle extracts of virus-free conifer seedlings,
      both IC-RT-PCR assays detected their respective target viruses at concentrations
      of 10-100 fg ml(-1). This compared to ELISA detection sensitivities of 1 ng ml(
      1). Primers were designed from regions of high sequence diversity. Specificity of
      all primer pairs was confirmed by sequencing of PCR products. PCR distinguished
      more reliably between the two viruses than ELISA. Moreover, a multiplex IC-RT-PCR
      assay for the simultaneous detection and differentiation of TMV and ToMV was
      developed. When root extracts were seeded with both viruses simultaneously, the
      multiplex assay detected each virus at concentrations of 1-10 pg ml(-1). Six TMV
      and 18 ToMV isolates from various hosts, water samples and a soil sample were
      amplified and differentiated by multiplex IC-RT-PCR. No amplifications were
      observed against pepper mild mottle and ribgrass mosaic tobamoviruses and against
      six viruses belonging to other taxonomic groups.

PMID- 9779617
TI  - A comparison of two RNA isolation methods for double-stranded RNA of infectious
      bursal disease virus.
AB  - Infectious bursal disease virus (IBDV), a member of the birnaviridae family,
      contains a bisegmented double-stranded RNA (dsRNA) genome. The segments are
      linked covalently at 5' termini by a large (90 kDa) viral genomic protein that
      migrates similar to viral RNA dependent RNA polymerase of IBDV. A proteinase K
      digestion based approach and acid-guanidium-phenol-chloroform (AGPC) RNA
      extraction method were used to extract dsRNA of IBDV from infected bursae. After
      extraction, dsRNA of IBDV was purified by precipitation with lithium chloride.
      The yield and purity of dsRNA of IBDV extracted by AGPC method was lower than
      that of proteinase K digestion based approach. This observation correlates with
      the presence of a genome-linked protein in IBDV. Although dsRNA obtained by both
      methods are suitable for reverse transcription-polymerase chain reaction (RT-PCR)
      amplification of at least up to 1201 base pairs (bp) of cDNA, dsRNA extracted by
      the proteinase K digestion method is more suitable than that by AGPC method for
      the amplification of longer fragments (1958 bp) of IBDV cDNA by PCR.

PMID- 9779618
TI  - Multicyclic reverse transcription-polymerase chain reaction assay system for
      quantification of GB virus-C/hepatitis G virus RNA in serum.
AB  - A new quantitative reverse transcription-polymerase chain reaction (RT-PCR)
      method is described for analyzing the amount of GB virus-C (GBV-C)/hepatitis G
      virus (HGV) RNA in serum. This multicyclic RT-PCR (MRT-PCR) method used
      oligonucleotide primers deduced from the 3' noncoding region (3'NCR) that is
      highly conserved among GBV-C/HGV isolates. Quantitation of GBV-C/HGV RNA using
      MRT-PCR ranged between 10(2) and 10(10) copies/ml when PCR cycle number was
      regulated at exponential amplification of the products. Competitive RT-PCR (CRT
      PCR) was carried out with mutant RNA and sample that had been measured by MRT
      PCR. Quantitation of GBV-C/HGV RNA using both methods agreed. MRT-PCR detected
      viral RNA in a single step PCR, and demonstrated a high degree of sensitivity
      that was equal to that of the RT-PCR procedure, which used nested primers deduced
      from the non-structural (NS) 3 region. The MRT-PCR method for quantitation of GBV
      C/HGV RNA in serum may prove useful for diagnosis.

PMID- 9779619
TI  - Strain specific recombinant antibodies to potato virus Y potyvirus.
AB  - Single chain Fv antibody fragments have been selected from a synthetic phage
      antibody library following three and four rounds of affinity selection with
      purified potato virus Y, common strain (PVY(O)). The selected fragments were
      highly specific for PVY and detected seven out of nine isolates of PVY(O) whilst
      failing to detect three isolates of PVY(N) and 12 isolates of PVY(NTN).
      Nucleotide sequence of the scFv genes showed the variable heavy fragments
      belonged to the human VH4 family, whilst the variable light fragments belonged to
      the Vlambda1 family. The fragments were used in ELISA to detect virus at
      concentrations of 50 ng/ml in plant sap and in comparisons with commercially
      available PVY monoclonal antibodies were shown to have similar limits of
      detection. This is the first report of the selection of a scFv specific for a
      member of the potyviridae, and its use in detecting and differentiating strains
      of PVY in infected plant sap. The results highlight the potential of the
      technology for the selection of strain specific antibodies with an avidity
      equivalent to traditional monoclonal antibodies raised against viral pathogens
      and their use for viral diagnosis.

PMID- 9779620
TI  - Specific detection of monkeypox virus by polymerase chain reaction.
AB  - The open reading frame coding for the A-type inclusion body protein (ATI) of
      monkeypox virus (MPV) was identified and sequenced for two strains. Nucleotide
      sequence comparison revealed 72-95.3% homology with the reported open reading
      frame sequences of the ATIs of other orthopoxvirus species, such as variola,
      vaccinia, cowpox, ectromelia, and camelpox viruses. Each MPV strain contained an
      8-bp deletion, which caused a frameshift that introduced a premature stop in the
      open reading frame at base 2091 relative to the ATI open reading frame of cowpox
      virus strain Brighton. The sequences enabled a primer pair to be designed that
      flanked the deletion and specifically amplified a 601-bp fragment that identified
      and differentiated 19 MPV strains examined from five other Old World
      orthopoxvirus species examined. The specificity was confirmed by cleavage of the
      19 MPV strain amplicons with BglII, which produced three subfragments of expected
      sized, based on the determined MPV sequences.

PMID- 9779621
TI  - Hepatitis E virus RNA detection in serum and feces specimens with the use of
      microspin columns.
AB  - This report describes the use of microspin columns for extraction of hepatitis E
      virus (HEV) RNA from stool and serum specimens for reverse transcription
      polymerase chain reaction (RT-PCR) and compares this method with the glass powder
      method. The microspin column method was found to be 1- to 2-log more sensitive in
      detecting HEV RNA than the glass powder method and had better reproducibility.
      The microspin column method also detected HEV RNA in a larger number of specimens
      than the glass powder method from among a panel of serum and stool specimens. Use
      of this method may allow better assessment of viremia and fecal excretion in
      patients and experimental animals infected with HEV.

PMID- 9779622
TI  - A procedure for detecting selection in highly variable viral genomes: evidence of
      positive selection in antigenic regions of capsid protein VP1 of foot-and-mouth
      disease virus.
AB  - A new procedure is described for the detection of positive selection among
      sequences of viral proteins from highly variable viruses. The approach is based
      on the estimation of the rates of nonsynonymous to synonymous (ns/s) mutations to
      the overall genetic distances amongst the sequences compared. Rates of ns/s
      substitutions were calculated, and the individual profiles were arranged as a
      function of the genetic distance observed between the complete sequences. The
      resulting surfaces allowed identification of protein regions whose rates of ns/s
      substitutions were consistent with the existence of positive selection. This
      procedure has been applied to the study of a highly variable antigenic protein,
      VP1, a protein present in foot-and-mouth disease virus (FMDV). The analysis of
      groups of VP1 sequences corresponding to FMDV serotypes A, O and C, resulted in
      the identification of two regions, which contribute to an important antigenic
      site, where positive selection appears to operate.

PMID- 9779623
TI  - Preservation of plant cell ultrastructure during immunolocalization of virus
      particles.
AB  - Most immunoelectron microscopy techniques used for ultrastructural analyses of
      virus-infected plant tissues significantly compromise cellular membranous
      structures as well as overall contrast and resolution of the image. Here, we
      describe a protocol which avoids these flaws but retains full antigenicity of the
      sample. A direct comparison of the conventional and the improved electron
      immunostaining procedures is presented using tobacco and Arabidopsis thaliana
      plants infected with turnip vein clearing virus.

PMID- 9779624
TI  - Use of citric acid for neutralizing polymerase chain reaction inhibition by
      chlorogenic acid in potato extracts.
AB  - Polyphenolics are a widely distributed class of plant constituents implicated in
      the inhibition of the polymerase chain reaction (PCR). Since chlorogenic acid
      forms the bulk of phenolics in the potato tuber, a range of chlorogenic acid
      concentrations were tested for inhibition of reverse transcription (RT) and PCR
      steps. The RT step was inhibited at chlorogenic acid concentrations of 6.0 to 7.5
      microg, while the PCR step was inhibited at much lower concentrations of 1.2 to
      1.8 microg. Incorporation of 1.2% citric acid at the nucleic acid extraction step
      prevented darkening of the extract and neutralized the inhibitory effect of
      chlorogenic acid.

PMID- 9779625
TI  - Radiologic staging of gastrointestinal cancer.
AB  - Pre-operative staging should define the probable course of a patient's disease,
      separate the resectable from the unresectable patients, and identify the patients
      who are candidates for induction therapy. Pre-operative staging must be well
      tolerated and should provide new or important information that will affect the
      proposed treatment plan. For some diseases such as colon cancer, pre-operative
      staging is largely unnecessary, but it can be of great value for other tumors
      such as pancreatic cancer. Currently, many imaging techniques are available to
      evaluate gastrointestinal cancers, and each provides information necessary for
      directing treatment. Although no individual technique can stage patients with
      complete accuracy, combinations of the various imaging techniques can be used to
      increase accuracy and promote appropriate decisions about an individual's
      treatment options. The use of current imaging techniques for staging primary
      lesions, regional spread, and the intra-abdominal metastatic spread of the most
      common gastrointestinal malignancies are reviewed.

PMID- 9779626
TI  - Pneumoperitoneum in the cancer patient: advantages and pitfalls.
AB  - The use of pneumoperitoneum to create a working environment for laparoscopic
      surgery may have both beneficial and detrimental effects in cancer patients.
      Studies suggest that immune mechanisms are protected when laparoscopic procedures
      are used and this does not seem to be compromised by the use of gas in the
      abdomen. Potential pitfalls in the utilization of pneumoperitoneum include the
      effects of hypothermia, cardiovascular consequences, hypercoagulability with
      associated deep-venous thrombosis, and the possibility that trocar-site
      recurrences may be produced by using a pneumoperitoneum. No concrete evidence of
      either beneficial or detrimental effects from pneumoperitoneum in cancer patients
      currently exists. Studies utilizing animal models and humans should be supported
      in this extremely important area.

PMID- 9779628
TI  - Role of laparoscopic ultrasound in cancer management.
AB  - Laparoscopic ultrasound (LUS) has become an important tool in the staging of
      hepatic, pancreatic, and gastrointestinal malignancies. It also plays an
      important role in the palliation and treatment of these malignancies. The use of
      laparoscopy and LUS in diagnosis, staging, palliation, and treatment of intra
      abdominal malignancies is discussed, with a focus on the literature and our own
      experience.

PMID- 9779627
TI  - Laparoscopic evaluation in pancreatic cancer.
AB  - Pancreatic cancer continues to carry a poor overall prognosis. The majority of
      patients have advanced disease at the time of presentation. Dynamic, contrast
      enhanced computed tomography (CT) has become the radiographic study of choice in
      the pre-operative staging of patients with pancreatic cancer. While it has been
      shown to be highly sensitive in determining unresectability of peri-ampullary
      tumors, the ability of CT to predict accurately which tumors can be safely
      resected is still limited. Laparoscopic staging of peri-ampullary tumors is
      superior to dynamic CT in visualizing small liver and peritoneal metastases. The
      addition of laparoscopic ultrasound during laparoscopic staging enhances the
      ability of laparoscopy to determine resectability of these tumors and approaches
      the accuracy of open exploration without increasing significant morbidity or
      mortality. Patients who are deemed unresectable at the time of laparoscopy can
      undergo palliative biliary and/or gastric bypass procedures laparoscopically and
      further minimize the morbidity of laparotomy.

PMID- 9779630
TI  - Combined laparoscopic and flexible endoscopic techniques in the management of
      malignant gastrointestinal lesions.
AB  - Most malignancies of the gastrointestinal tract rise from intraluminal sources.
      Endoscopic evaluation for diagnosis and treatment of these disease processes is a
      very accurate and inexpensive method compared with non-endoscopic methods alone.
      Combined laparoscopic and flexible endoscopic techniques greatly facilitate
      laparoscopic treatment of a significant number of gastrointestinal tract
      malignancies that might otherwise require a conventional open approach. The
      theory of combining the procedures of laparoscopy and endoscopy to identify and
      treat malignant lesions of the gastrointestinal tract is described as well as the
      techniques, advantages, and problems encountered. At our institution, the
      combination of these two fields of technology has resulted in improved patient
      care with a low complication rate.

PMID- 9779629
TI  - Laparoscopic evaluation of lymphoma.
AB  - Surgeons are involved in the diagnosis and staging of patients with lymphoma.
      Treatment requires accurate information about histologic classification and the
      extent of disease. While most patients with non-Hodgkin's lymphoma are treated
      with systemic chemotherapy, the exact stage of disease in patients with Hodgkin's
      lymphoma may determine the therapy to be used. The use of minimally invasive
      surgery in surgical staging of patients with Hodgkin's disease has the potential
      to decrease the morbidity and mortality of the staging procedure in these
      patients. All of the components of a staging procedure (liver biopsies,
      splenectomy, lymph node biopsies, and oophoropexy) can be performed
      laparoscopically. The procedure is performed with the patient in the supine
      position. After obtaining several liver biopsies, the splenectomy is completed.
      Lymph nodes are then sampled from the celiac, portal, iliac, and peri-aortic
      regions. Lymph nodes identified as abnormal on pre-operative imaging studies are
      identified and excised. While each of these procedures is technically
      challenging, the laparoscopic conduct of this diagnostic procedure may afford
      patients decreased post-operative morbidity and mortality.

PMID- 9779631
TI  - Port-site metastasis in the abdominal wall: fact or fiction?
AB  - Port-site metastasis (PSM) following minimally invasive surgery (MIS) is
      discussed and four points are addressed: 1) the occurrence of PSM; 2) the
      occurrence of PSM as part of distant metastasis, and the need for more studies to
      confirm that it can occur purely as implantation metastasis; 3) the preliminary
      experimental evidence suggesting that carbon dioxide might have a role in PSM and
      that viable cells can be dispersed by pneumoperitoneum (with more experimental
      work and clinical studies needed to confirm these observations); and 4) some
      studies showing an increased incidence of PSM after MIS compared with open
      surgery. Prospective randomized studies with adequate follow-up are needed to
      establish the validity of such reports.

PMID- 9779632
TI  - Laparoscopic cryoablation of hepatic metastases.
AB  - Cryosurgery for liver metastases may improve survival for unresectable hepatic
      metastases. The laparoscopic approach to managing these tumors is a novel method
      fostered by increasing surgeon and patient interest in minimally invasive
      surgical techniques and the development of laparoscopic ultrasound and
      cryoprobes. A retrospective review of our patients who underwent laparoscopic
      cryoablation of hepatic tumors from April 1996 to December 1997 was conducted. We
      report on this experience and comment on the feasibility and safety of the
      procedure based on this early trial.

PMID- 9779633
TI  - History of vein grafting.
AB  - Microsurgical vein grafting for vessel reconstruction has its roots in the
      vascular surgery of 100 years ago. It was not until the 1950s that vein grafts
      became more common for treating traumatic, atherosclerotic, and aneurysmal
      lesions. The success and popularization of extremity replantation quickly led to
      the utilization of vein grafts in select cases. Current practices use vein grafts
      whenever needed to bridge gaps in vessel continuity during reconstructive
      microsurgery.

PMID- 9779634
TI  - Role of vein grafts in reconstructive microsurgery.

PMID- 9779635
TI  - Use of vein loops in reconstructive procedures.
AB  - The use of a temporary arteriovenous fistula prior to flap harvesting was
      suggested by Threlfall in 1982 (Threlfall, Aust NZ J Surg 52:182-184, 1982). The
      basic idea is to use long venous grafts that can be branched side-to-end to a
      main artery at an easily accessible level using one of the well-established
      exposures from general vascular surgery. In reconstructive microsurgery, AV-loops
      are used in limb salvage procedures and in cancer surgery. These patients have
      often undergone previous surgery and additional radiotherapy. AV-loops facilitate
      the use of normal recipient vessels out of the zone of injury, or far away from
      scar or irradiated tissue.

PMID- 9779636
TI  - Artery grafts in microsurgery.
AB  - Artery grafts appear to have no significant advantages over vein grafts in
      experimental models. Research in preservation of artery grafts continues, and
      holds possibilities of creating stored grafts that can be used clinically.
      Clinical use of artery grafts in microsurgery is limited to anecdotal use of
      arteries harvested from damaged body parts in emergencies and use of branched
      grafts from the subscapular system in elective arterial reconstruction. These
      clinical uses have never been analyzed, and their reliability and advantages
      remain undefined.

PMID- 9779637
TI  - Freeze-dried vessels as interpositional grafts in microsurgery.

PMID- 9779638
TI  - Synthetic microvascular prostheses.

PMID- 9779639
TI  - New concepts and materials in microvascular grafting: prosthetic graft
      endothelial cell seeding and gene therapy.
AB  - Microsurgical free tissue transfer is currently associated with very high success
      rates and few complications. While interposition vein grafting is clearly an
      important adjunct to the microsurgeon's armamentarium, it has been associated
      with higher free flap/replantation failures and complication rates. With
      appropriate flap planning and surgical techniques, the need for interposition
      vein grafting should be quite infrequent and hopefully avoided if at all
      possible. Nevertheless, when necessary, the vein graft remains the gold standard,
      with virtually all alternative interposition grafts demonstrating lower patency
      rates. One of the more promising areas of research is the concept of genetic
      manipulation of the endothelial cell via molecular biological techniques. It is
      likely that in the near future this may become a clinical reality, not only
      improving the patency of microsurgical anastomoses and interposition vein grafts,
      but quite possibly altering the target organ functionally as well.

PMID- 9779640
TI  - A more versatile and reliable method for renal transplantation in the rat.
AB  - This study describes the authors' experience with a new method of orthotopic
      renal transplantation in the rat. This technique combines previously described
      modifications with the use of the donor inferior vena cava as a conduit to
      perform an end-to-side venous anastomosis. Survival was 87% and 80% at 3 and 120
      days, respectively. Patency was 80% at 120 days, and histologic examination
      revealed normal renal architecture and parenchyma, with no evidence of ischemic
      injury. This technique offers a refinement of previous techniques and is
      reliable, flexible, and can be easily learned by novice microvascular surgeons.

PMID- 9779641
TI  - Hyaluronic acid enhances peripheral nerve regeneration in vivo.
AB  - Hyaluronic acid has been shown to enhance peripheral nerve regeneration in vitro.
      It has been proposed that, during the fibrin matrix phase of regeneration,
      hyaluronic acid organizes the extracellular matrix into a hydrated open lattice,
      thereby facilitating migration of the regenerating axons. Hyaluronic acid
      solutions and saline control solutions were injected into a nerve guide spanning
      a transected gap in the sciatic nerve of Sprague-Dawley rats (five in each
      group). Nerve conduction velocities were measured at 4 weeks by electromyography
      (EMG) before sacrifice of the animals. These studies demonstrated increased
      conduction velocities in the hyaluronic acid group compared with control animals
      (P = 0.006). After the animals were sacrificed, regenerated axon cables were
      quantified histologically, and axon branching was delineated by retrograde tracer
      analysis. In addition, the hyaluronic acid group showed an increase in myelinated
      axon counts at 4 weeks (P= 0.03). An increase in retrograde flow was demonstrated
      in the hyaluronic acid groups compared with animals receiving saline solution.

PMID- 9779642
TI  - Results of termino-lateral neurorrhaphy to original and adjacent nerves.
AB  - In this comprehensive investigation, we studied three different neurorrhaphy
      models in an attempt to elucidate the potential of termino-lateral nerve repair
      to original and adjacent nerves. In experimental group 1, the peroneal nerve was
      sectioned and then attached to the posterior tibial nerve in a termino-lateral
      fashion. In experiment group 2, the motor nerves to the gastrocnemius muscle were
      sectioned and then attached to the posterior tibial nerve in a termino-lateral
      fashion. In experimental group 3, the obturator nerve (L2-4) was sectioned and
      attached to the sciatic nerve (L4-6) in a termino-lateral fashion. For the
      control in each group, the same type of nerve used in each respective group was
      transected without repair. Experimental groups 1 and 2 showed viable axons in the
      peroneal nerve distal to the neurorrhaphy site. Experimental group 3 showed no
      viable axons at these sites. No regeneration was observed in the transected nerve
      without repair in all three control groups. This study suggests that termino
      lateral neurorrhaphy is a viable means of repairing damaged nerves if the distal
      segment of the sectioned nerve is reattached to its original trunk distal to its
      original branch point. However, the results from experimental group 3 demonstrate
      that termino-lateral neurorrhaphy cannot be used to repair nerves when the donor
      and recipient nerves originate from different spinal cord levels.

PMID- 9779643
TI  - Complete ear replantation without venous anastomosis.
AB  - Traumatic amputation of the entire auricle is a rare occurrence. Management
      ideally consists of microvascular reconstruction of auricular arterial, venous,
      and nerve continuity. However, appropriately sized veins are often not available
      and venous drainage must be accomplished with leech therapy. In occasional cases
      where leeches are unavailable or cannot be made to attach, mechanical drainage
      and anticoagulation can give satisfactory drainage. The authors present a case of
      mechanical wick venous drainage of a complete ear replantation, resulting in
      virtually normal appearance and function of the ear. In addition, the ear
      regained normal touch and two-point sensibility, although the great auricular
      nerve had not been repaired.

PMID- 9779644
TI  - Facial nerve palsy: which flap? Microsurgical, anatomical, and functional
      considerations.
AB  - In the microsurgical therapy of facial nerve palsy, the muscles most frequently
      utilized have been gracilis, latissimus dorsi, and pectoralis minor, this
      depending upon surgeons' personal experience. However, at the moment no
      satisfactory comparison studies are available; this work is a comparative study
      of the three most often used cadaver-derived muscles in surgical therapy of
      facial nerve palsy. The potential use of gracilis, latissimus dorsi, and
      pectoralis minor as free flaps has been assessed by analyzing their
      microsurgical, anatomical and functional parameters. Suitability has been
      evaluated by scoring each parameter from 0 to 3 (unsatisfactory, satisfactory,
      good, and excellent respectively). The results may provide the surgeon who
      undertakes this kind of technique with a useful data comparison.

PMID- 9779645
TI  - Leukocyte behavior in a free-flap model following chemotherapy and application of
      granulocyte colony-stimulating factor (GCSF).
AB  - Free-flap reconstruction following tumor resection and chemotherapy is used
      increasingly in sarcoma patients. Granulocyte colony-stimulating factor (GCSF) is
      used to stimulate polymorphnuclear leukocytes (PMNs). In this study we used a
      free-flap model to investigate PMN behavior after chemotherapy and GCSF
      stimulation. Eighteen Lewis rats were divided into three groups: (1) chemotherapy
      + vehicle; (2) chemotherapy + GCSF; and (3) control. Group 1 received
      vinblastine; group 2 received vinblastine plus 300 microg rhGCSF. Blood was drawn
      for total white cell and PMN counts for 9 days. Free-flap surgery was simulated
      by isolating the cremaster muscle on its pedicle and anastomosing the artery.
      Leukocyte-endothelium interaction was assessed by observation of leukocytes
      rolling and sticking. Leukocyte sequestration was measured by counting leukocytes
      in the lungs and the abdomen. We found that leukocyte rolling and sticking were
      significantly increased, while sequestration was decreased in the chemotherapy +
      GCSF group. We conclude that leukocytes-endothelium interaction after
      chemotherapy and GCSF administration is increased in the microcirculation. This
      augments the risk of microvascular compromise and subsequent flap failure, as
      capillary flow may be altered.

PMID- 9779646
TI  - Laser treatment of solar elastosis with epithelial preservation.
AB  - BACKGROUND AND OBJECTIVE: Laser resurfacing has gained wide acceptance for the
      treatment of actinic facial skin. However, postoperative care of the face is
      reasonably complicated and prolonged erythema is common. To simplify the
      postoperative care and to possibly reduce the duration of the erythema, we
      investigated a laser treatment that spares the epithelium. STUDY DESIGN/MATERIALS
      AND METHODS: A 980 nm diode laser was used with a spherical optic handpiece to
      focus the light in the dermis. We treated in vitro breast and facial skin and
      measured the tissue shrinkage and the histological changes. We also treated two
      patients and harvested the tissue after 6 and 21 days of wound healing. RESULTS:
      The diode laser treatment does not ablate the epidermis. The tissue shows
      shrinkage (16% at 8W) similar to three passes of the scanned carbon dioxide laser
      treatment (15%). Thermal damage in the dermis is similar to the residual damage
      left after laser resurfacing with the scanned carbon dioxide laser. After 21 days
      the tissue shows new collagen and an abundance of young elastin fibers.
      CONCLUSIONS: These investigations indicate that solar elastosis in skin can be
      treated with the 980 nm diode laser while preserving the epithelial layer.

PMID- 9779647
TI  - Saline flush during excimer laser angioplasty: short and long term effects in the
      rabbit femoral artery.
AB  - BACKGROUND AND OBJECTIVE: In this study, the effect of flushing saline on
      arterial wall damage (medial ruptures and necrosis), intimal hyperplasia, and
      arterial remodeling was determined. During excimer laser coronary angioplasty
      saline is flushed to reduce the size of explosive water vapor bubbles formed by
      intraluminal delivery of excimer laser pulses in blood. METHODS: In the femoral
      artery of the rabbit, 600 excimer laser pulses (308 nm, 50 mJ/mm2 per pulse, 20
      Hz) were delivered coaxially over a length of 20 mm in 10 bursts of 3 seconds
      each. In 24/48 procedures, saline was flushed (0.2 ml/s) via the guidewire
      channel. After 2 and 56 days, microscopic and angiographic results were compared.
      RESULTS: At 2 days, as compared to lasing in blood, saline flush had drastically
      reduced the incidence of dissections (2/12 vs. 11/12, P < 0.002), but had
      increased the extent of medial and adventitial necrosis. The latter is attributed
      to direct irradiation of the arterial wall. After 56 days, in the saline group,
      in the middle-distal part of treated segments, medial necrosis without intimal
      hyperplasia was observed. However, at the edges of these lesions, intimal
      hyperplasia and arterial shrinkage reduced the lumen. CONCLUSION: Flushing saline
      during coaxial excimer laser pulse delivery significantly reduced the incidence
      of vessel wall ruptures, and prevented intimal hyperplasia formation in part of
      the lesion. The histologic findings at 56 days are attributed to the optical
      window which the saline flush provides for direct ultraviolet light irradiation
      of the arterial wall.

PMID- 9779648
TI  - Safe parameters for laser chondroplasty of the knee.
AB  - BACKGROUND AND OBJECTIVE: The purpose of this study is to summarize our use of
      the Holmium laser as a tool in performing chondroplasties of the knee and to
      determine whether any untoward affects developed at the site of laser
      application. STUDY DESIGN/MATERIALS AND METHODS: A retrospective review of 504
      laser chondroplasties of the medial femoral condyle was done. Laser parameters
      and the average number of joules to perform the chondroplasties were recorded.
      The average follow-up was 11 months. RESULTS: Preoperative MRI interpretation
      indicated that 8% of the patients had osteonecrosis prior to surgery. 88% of the
      patients were satisfied with the procedure. All failures were evaluated by X-ray,
      MRI, bone scan, or biopsy of the medial femoral condyle. No new cases of
      osteonecrosis were determined. CONCLUSION: No new cases of osteonecrosis were
      documented of the medial femoral condyle following laser chondroplasty utilizing
      the parameters in this study. The Holmium laser remains a safe and efficacious
      tool in performing chondroplasty.

PMID- 9779649
TI  - Enhanced laser thrombolysis with photomechanical drug delivery: an in vitro
      study.
AB  - BACKGROUND AND OBJECTIVE: Current techniques for laser thrombolysis are limited
      because they can not completely clear thrombotic occlusions in arteries,
      typically leaving residual thrombus on the walls of the artery. The objective of
      this study was to investigate the possibility of using photomechanical drug
      delivery to enhance laser thrombolysis by delivering drugs into mural thrombus
      during laser thrombolysis. STUDY DESIGN/MATERIALS AND METHODS: Three experimental
      protocols were performed in vitro to quantitatively compare the effectiveness of
      thrombolysis by 1) constant infusion of drug, 2) laser thrombolysis, and 3)
      photomechanical drug delivery. A fiber-optic flushing catheter delivered drug (a
      solution of 1 microm fluorescent microspheres) and light ( a 1 micros pulsed dye
      laser) into a gelatin-based thrombus model. The process of laser-thrombus
      interaction was visualized using flash photography and the laser-induced pressure
      waves were measured using an acoustic transducer. RESULTS: Lumen sizes generated
      by mechanically manipulating the catheter through the thrombus were smaller than
      those generated by laser ablation. The microspheres could be driven several
      hundred microns into the mural thrombus. CONCLUSION: Photomechanical drug
      delivery has potential for enhancement of laser thrombolysis. Two mechanisms seem
      to be involved in photomechanical drug delivery: 1) mural deposition of the drug
      at the ablation site and 2) increased exposure of the thrombus surface area to
      the drug.

PMID- 9779651
TI  - Evaluation of topical anesthetics by laser-induced sensation: comparison of EMLA
      5% cream and 40% lidocaine in an acid mantle ointment.
AB  - BACKGROUND AND OBJECTIVE: Current techniques for assessing local anesthetics
      (e.g., pin-prick test) cannot elicit a specific afferent activity without
      contamination from mechanosensitive receptors. This study was aimed to validate
      the use of non-scarring laser pulses as a reproducible method to assess
      effectiveness of topical anesthetics by comparing EMLA 5% cream and 40% lidocaine
      ointment. STUDY DESIGN/MATERIALS AND METHODS: Thirty-two evaluations per compound
      were achieved in a total of eight healthy subjects. Non-scarring pulses from a
      585 nm Pulsed-dye laser and a double-frequency Nd:YAG laser were investigated as
      pain inducers and the results were statistically analyzed by using a Student t
      test. RESULTS: Discrimination of anesthesia was better assessed with the 1,064 nm
      Nd:YAG laser. Anesthesia obtained by EMLA 5% cream was significantly higher than
      for 40% lidocaine ointment (P <0.0001). For EMLA cream, the number of evaluations
      with complete anesthesia was twice as much as for 40% lidocaine. CONCLUSIONS: Non
      scarring laser pulses are reliable and reproductive pain inducers for assessing
      topical anesthetics showing a low intra-individual variation. This technique
      demonstrated that EMLA 5% cream is significantly more effective than 40%
      lidocaine ointment.

PMID- 9779650
TI  - Photodynamic therapy using Photofrin in combination with buthionine sulfoximine
      (BSO) to treat 9L gliosarcoma in rat brain.
AB  - BACKGROUND AND OBJECTIVE: The reactive oxygen mechanisms associated with cell
      damage after photodynamic therapy (PDT) may be exploited to enhance tumor
      destruction. Pharmacological reduction of glutathione (GSH), an inhibitor of
      reactive oxygen species, can be induced by administration of buthionine
      sulfoximine (BSO). STUDY DESIGN/MATERIALS AND METHODS: BSO was administered in
      combination with Photofrin as the photosensitizer in order to promote PDT induced
      cell damage. Photofrin (12.5 mg/kg) or Photofrin with BSO (440 mg/kg) were
      administered to male Fischer rats (n = 27) containing an intracerebral 9L
      gliosarcoma or to non tumored rats. Brain tumor or non tumored brain was treated
      with an optical (632 nm) irradiance of 140 J/cm2. Animals were sacrificed 24 h
      after PDT and the volume of tissue necrosis was measured. Brain Photofrin
      concentration was measured in tumor and in non tumor bearing animals administered
      either Photofrin or Photofrin with BSO. GSH was measured by high pressure liquid
      chromatography in tumor and homologous non tumor tissue in animals administered
      BSO or control solution. RESULTS: The volume of tumor necrosis was significantly
      greater in animals administered Photofrin and BSO than in animals administered
      only Photofrin. No differences were detected in non tumored tissue damage between
      groups. No differences in Photofrin concentration were detected in tumored or
      nontumored animals between animals administered Photofrin and animals
      administered Photofrin and BSO. BSO administration preferentially and
      significantly reduced GSH in tumor compared to non tumor tissue. CONCLUSIONS: Our
      data suggest that BSO administration preferentially augments tumor destruction
      without compromising non tumored tissue.

PMID- 9779652
TI  - Microbiologic activity in laser resurfacing plume and debris.
AB  - BACKGROUND AND OBJECTIVE: With the increasing use of laser resurfacing, concerns
      have arisen about the biological hazards associated with the procedure. This
      study analyzed the potential bacterial and viral exposure to operating room
      personnel as a result of the laser smoke plume in CO2 laser resurfacing. STUDY
      DESIGN/MATERIALS AND METHODS: Thirteen consecutive patients underwent CO2 laser
      resurfacing. A HEPA filter in the smoke evacuator was used to collect specimens
      of the laser plume smoke for cultures. The study was controlled by a second
      filter exposed to room air. RESULTS: The 13 patients each had one bacterial, one
      viral, and one control culture (total, 39 specimens). In the control group, none
      of the 13 specimens had any growth. No viral growth has been found to date. Of 13
      bacterial cultures, 5 resulted in growth of coagulase-negative Staphylococcus. Of
      these five positive specimens, one also had growth of Corynebacterium and one had
      growth of Neisseria. CONCLUSION: The potential exists for operating personnel to
      be exposed to viable bacteria during laser resurfacing.

PMID- 9779653
TI  - What's up?

PMID- 9779654
TI  - The Human Genome Project: applications in the diagnosis and treatment of
      neurologic disease.
AB  - The Human Genome Project (HGP), an international program to decode the entire DNA
      sequence of the human genome in 15 years, represents the largest biological
      experiment ever conducted. This set of information will contain the blueprint for
      the construction and operation of a human being. While the primary driving force
      behind the genome project is the potential to vastly expand the amount of genetic
      information available for biomedical research, the ramifications for other fields
      of study in biological research, the biotechnology and pharmaceutical industry,
      our understanding of evolution, effects on agriculture, and implications for
      bioethics are likely to be profound.

PMID- 9779655
TI  - Inborn and induced defects of mitochondria.
AB  - Mitochondria play a pivotal role in cellular metabolism and in energy production
      in particular. Predictably, defects of mitochondrial metabolism have a
      deleterious effect on cell function and survival, especially in highly energy
      dependent tissues such as brain and skeletal muscle. Although a multitude of
      biochemical reactions occur within mitochondria, the oxidative phosphorylation
      (OXPHOS) system is the most important in terms of adenosine triphosphate
      generation and in its association with human disease.

PMID- 9779656
TI  - Brain glyceraldehyde-3-phosphate dehydrogenase activity in human trinucleotide
      repeat disorders.
AB  - BACKGROUND: Although the abnormal gene products responsible for several
      hereditary neurodegenerative disorders caused by repeat CAG trinucleotides have
      been identified, the mechanism by which the proteins containing the expanded
      polyglutamine domains cause cell death is unknown. The observation that several
      of the mutant proteins interact in vitro with the key glycolytic enzyme
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) suggests that interaction
      between the different gene products and GAPDH might damage brain neurons.
      OBJECTIVE: To measure the activity of GAPDH in postmortem brain of patients with
      CAG repeat disorders. PATIENTS AND METHODS: Activity of GAPDH was measured in
      morphologically affected and unaffected brain areas of patients with 4 different
      CAG repeat disorders (Huntington disease, spinocerebellar ataxia 1 [SCA1], SCA2,
      and SCA3-Machado-Joseph disease), in brains of patients with Friedreich ataxia (a
      GAA repeat disorder) and Alzheimer disease, and in brains of matched control
      subjects. RESULTS: Brain GAPDH activity was normal in all groups with the
      exception of a slight but statistically significant region-specific reduction in
      the patients with Huntington disease (caudate nucleus, -12%) and Alzheimer
      disease (temporal cortex, -19%). CONCLUSION: The presence of the polyglutamine
      containing proteins in CAG repeat disorders does not result in substantial
      irreversible inactivation or in increased activity of GAPDH in human brain.

PMID- 9779657
TI  - T-lymphocyte interleukin 6 receptor binding in patients with dementia of
      Alzheimer type.
AB  - OBJECTIVE: To investigate some aspects of T-cell-dependent immune function in
      patients with dementia of the Alzheimer type (DAT). DESIGN: Assay of interleukin
      6 binding on T lymphocytes from patients with DAT, compared with that in healthy
      controls. SETTING: The study included ambulatory patients in a tertiary care
      center who were diagnosed as having DAT according to the criteria of the National
      Institute of Neurologic and Communicative Disorders and Stroke. SUBJECTS: Thirty
      five patients with DAT without depression (15 women and 20 men; mean +/- SD age,
      68.6 +/- 15.8 years) were selected consecutively. They had not taken any
      medication for at least 3 weeks and did not smoke. Illness severity was evaluated
      according to the Clinical Dementia Rating Scale. Thirty-five age- and sex-matched
      healthy nonsmoking subjects with no family history of neuropsychiatric disorders
      formed the control group. RESULTS: A significant (P < .001) increase in T
      lymphocyte interleukin 6 binding was found in patients with DAT compared with
      healthy controls (mean +/- SE receptors per cell, 305 +/- 7 vs 276 +/- 6,
      respectively), whereas the ligand-receptor affinity values were similar in the 2
      groups (mean +/- SE, 25.9 +/- 0.9 and 25.3 +/- 0.6 nmol/L). CONCLUSION: These
      data indicate a derangement of the immune response in patients with DAT since
      cell-surface interleukin 6 receptors seem to be related to T-lymphocyte immune
      function.

PMID- 9779658
TI  - Neuropsychiatric assessment of patients with hyperkinetic and hypokinetic
      movement disorders.
AB  - BACKGROUND: The role of the basal ganglia in neuropsychiatric behaviors is not
      well known. Anatomical, neurophysiological, and neurochemical evidence supports
      the notion of parallel direct and indirect basal ganglia thalamocortical motor
      systems, the differential involvement of which accounts for the hypokinesia or
      hyperkinesia observed in basal ganglia disorders. OBJECTIVES: To evaluate the
      neuropsychiatric manifestations of patients with a hyperkinetic movement
      disorder, such as Huntington disease (HD), vs a hypokinetic disease, such as
      progressive supranuclear palsy (PSP). To verify if patients with HD show a
      greater frequency of hyperactive behaviors (eg, agitation, irritation, euphoria,
      or anxiety), while those with PSP exhibit hypoactive behaviors (eg, apathy).
      PATIENTS AND METHODS: The Neuropsychiatric Inventory, a tool with established
      validity and reliability, was administered to 29 patients with HD (mean +/- SD
      age, 43.8 +/- 2 years) and 34 with PSP (mean +/- SD age, 66.6 +/- 1.2 years),
      matched for education, symptom duration, and overall degree of dementia. RESULTS:
      There was no difference between the groups in the total Neuropsychiatric
      Inventory scores. However, there was a double dissociation in behaviors: patients
      with HD exhibited significantly more agitation (45%), irritability (38%), and
      anxiety (34%), whereas patients with PSP exhibited more apathy (82%) (P < .01).
      Euphoria was present only in patients with HD. CONCLUSIONS: We found that
      patients with HD manifested predominantly hyperactive behaviors, while those with
      PSP manifested hypoactive behaviors. Based on our findings and the anatomical
      lesions known to occur in these disorders, we suggest that the hyperactive
      behaviors in HD are secondary to an excitatory subcortical output through the
      medial and orbitofrontal cortical circuits, while in PSP the hypoactive behaviors
      are secondary to hypostimulation.

PMID- 9779659
TI  - Long-term follow-up of levodopa responsiveness in generalized dystonia.
AB  - OBJECTIVES: To assign an accurate diagnosis to patients with dystonia based on
      the presence of sustained levodopa responsiveness and to determine whether motor
      fluctuations occur in patients with dystonia who are withheld from levodopa.
      PATIENTS AND METHODS: Patients with generalized dystonia who responded to
      treatment in the 1970s with levodopa/carbidopa were surveyed by phone and then
      examined during a 3-day levodopa holiday. Functional imaging with fluorodopa
      positron emission tomography was performed on a subset of patients. RESULTS: In
      the phone interview, 4 of 7 patients with a diagnosis of dopa-responsive dystonia
      reported the wearing-off effect a short while (within 4-8 hours) after missing a
      dose of levodopa. Five patients with dopa-responsive dystonia were examined
      repetitively during levodopa withdrawal, and 3 developed recurrent symptoms of
      dystonia as the drug was withheld. In each case, worsening of dystonia did not
      occur until 29 hours or more after levodopa withdrawal, providing evidence for a
      response profile similar to the long duration response described in Parkinson
      disease. No significant changes were seen in the dystonia scores of the 3
      patients with idiopathic torsion dystonia who were withheld from levodopa.
      CONCLUSIONS: We suggest that the subjective feeling of wearing off experienced by
      our patients with dopa-responsive dystonia may have been for one of the nonmotor
      effects of levodopa, such as mood elevation. Our data provide objective evidence
      for the often-repeated assertion that motor fluctuations (analogous to those in
      levodopa-treated patients with Parkinson disease) do not occur in patients with
      dopa-responsive dystonia.

PMID- 9779660
TI  - Influence of head trauma on outcome following anterior temporal lobectomy.
AB  - BACKGROUND: There is controversy in the literature regarding the importance of
      risk factors in developing epilepsy and seizure outcome following anterior
      temporal lobectomy. Some of the existing studies may be biased because of patient
      selection and limitations in determining predisposition. OBJECTIVE: To
      investigate the role of risk factors for epilepsy in determining outcome
      following anterior temporal lobectomy. PATIENTS AND METHODS: We identified 102
      patients in a consecutive surgery series for epilepsy from a tertiary center with
      a minimum of 1-year postoperative follow-up. Risk factors for epilepsy were
      determined prospectively on at least 3 occasions before anterior temporal
      lobectomy. Risk factors investigated were a history of febrile convulsions,
      family history of epilepsy, significant head trauma, history of meningitis,
      history of encephalitis, or significant perinatal insult. Foreign tissue lesions
      on magnetic resonance imaging was also included if an anterior temporal lobectomy
      was performed for presumed dual pathologic findings (hippocampus and lesion).
      Outcome was determined using Engel's classification. For statistical analysis we
      used successive logistic regression analysis, chi(2) test, Fisher exact test, and
      t test. RESULTS: Of the 102 patients, 13 had no identified risk factor for
      epilepsy, 49 had 1 identified risk factor, and 40 had more than 1. Frequencies
      were 39 febrile convulsions (15 complex febrile convulsions), 29 head trauma, 22
      with lesions seen on magnetic resonance imaging, 12 history of meningitis, 2
      history of encephalitis, 19 family history of epilepsy, and 4 perinatal insult.
      Seventy-one (70%) were classified as Engel's class I, with 56 patients
      continuously free of seizures at follow-up. Those without risk factor were as
      likely to be rendered free of seizures following anterior temporal lobectomy as
      those with a risk factor (P = .27). No risk factor alone or in combination was
      correlated with complete freedom from seizures following anterior temporal
      lobectomy, but the presence of head trauma, alone or in combination, was
      correlated with continued seizures following anterior temporal lobectomy (P =
      .03; odds ratio, 2.6). Better outcomes were not seen in those with head trauma
      before the age of 5 years (P = .57). These findings did not change if all those
      with lesions on magnetic resonance imaging were excluded in the analysis. Those
      with a history of head trauma were as likely to have pathologic evidence of
      mesial temporal sclerosis as others (P = .82). CONCLUSIONS: Patients with a
      history of significant head trauma are less likely to become free of seizures
      following anterior temporal lobectomy. No other risk factor correlated with a
      statistically significant greater or lesser chance of freedom from seizures. This
      information may be used in preoperative counseling of patients.

PMID- 9779661
TI  - Alcohol-related acute axonal polyneuropathy: a differential diagnosis of Guillain
      Barre syndrome.
AB  - BACKGROUND: Chronic axonal polyneuropathy is a well-known clinical sequela of
      excessive alcohol consumption; however, acute axonal polyneuropathy related to
      alcohol abuse is less well recognized. OBJECTIVE: To describe alcohol-related
      acute axonal polyneuropathy in 5 chronic alcoholics who developed ascending
      flaccid tetraparesis and areflexia within 14 days. METHODS: Case series with
      clinical, laboratory, electrophysiological, and, in 1 patient, biopsy data.
      RESULTS: All 5 patients consumed a daily average of 250 g of alcohol, and 4 had
      lost a substantial amount of weight recently. Additional clinical features
      included painful paresthesia, myalgia, and glove and stocking-type sensory loss.
      Repeated cerebrospinal fluid examinations failed to show the marked increase of
      protein concentration with normal cell count typical of Guillain-Barre syndrome,
      although the protein level was mildly elevated in 1 patient. Blood laboratory
      findings were consistent with longstanding alcohol abuse. Compound muscle and
      sensory nerve action potentials were absent or reduced, while conduction
      velocities were normal or mildly reduced. Three to 4 weeks after onset, needle
      electromyography displayed moderate to severe fibrillations and positive sharp
      waves in addition to normal motor unit potentials, indicating an acute axonal
      polyneuropathy; this was confirmed by sural nerve biopsy in 1 patient.
      CONCLUSIONS: Excluding other factors, we assume that in these patients the
      combination of alcohol abuse and malnutrition caused severe acute axonal
      polyneuropathy. Its distinction from Guillain-Barre syndrome is important because
      treatment requires balanced diet, vitamin supplementation, and abstinence from
      alcohol, while immunotherapy may not be indicated.

PMID- 9779662
TI  - Dopamine receptor genetic variation, psychosis, and aggression in Alzheimer
      disease.
AB  - OBJECTIVE: To examine if selected polymorphisms in the dopamine receptor genes
      DRD1, DRD2, DRD3, and DRD4 are associated with the presence of psychosis or
      aggressive behavior in patients with Alzheimer disease (AD). DESIGN: A cohort of
      patients with AD were longitudinally evaluated for behavioral symptoms and
      classified with regard to the presence of psychotic symptoms and physical
      aggression. SETTING: Alzheimer's Disease Research Center. PATIENTS: Two hundred
      seventy-five elderly outpatients diagnosed as having probable AD. RESULTS: Among
      white patients, psychosis and aggression were both significantly more frequent in
      DRD1 B2/B2 homozygotes (P < .02), while psychosis was significantly more frequent
      in DRD3 1/1 or 2/2 homozygotes (P < .05). The joint risk for psychosis due to the
      DRD1 and DRD3 polymorphisms exceeded the risks due to either locus alone,
      suggesting an interaction. Neither the DRD2 S311C polymorphism nor the presence
      of long alleles for the DRD4 exon III repeat sequence was associated with
      psychosis or aggression. CONCLUSIONS: Genetic variation in DRD1 and DRD3 genes
      may act to modify the course of AD, predisposing to the development of psychotic
      or aggressive symptoms. Confirmation in other samples of patients with AD is
      required.

PMID- 9779663
TI  - Causes of death in Machado-Joseph disease: a case-control study in the Azores
      (Portugal).
AB  - BACKGROUND: Machado-Joseph disease (MJD) is an autosomal dominant cerebellar
      ataxia of adult onset with a high prevalence in the islands of Azores (Portugal).
      The genetic epidemiological studies presently under way in these islands are
      based on the genealogical reconstruction of the affected families, thus partially
      depending on the reference of patients using family history. A considerable
      effort has been made to obtain genealogies that are as complete as possible,
      making use of different types of data. The utility of the death causes contained
      in the death registers of the patients with MJD was determined in this study.
      OBJECTIVES: To estimate the extent to which the cause of death reported in the
      death register can confirm other reports of an individual's status for the
      disease (ie, oral information), and to determine the accuracy of the death
      certificates in listing MJD in patients whose disease was clinically diagnosed.
      DESIGN: Case-control study. METHODS: The death registers of 113 patients with MJD
      (82 whose disease was identified by history and 31 whose disease was clinically
      diagnosed) were examined and compared with those of controls matched by sex and
      date and place of death. RESULTS: There were significant differences in the
      causes of death between cases and controls, both for those whose disease was
      identified by history (chi(2) = 51.69, P < .001) and for those whose disease was
      identified by examination (chi(2) = 27.78, P = .004). However, the cause of death
      was in accord with the presence of the disease in only 40% of the cases reported
      as being identified only by family history. In the cases in which the disease was
      clinically diagnosed, only nearly 38% of the registers provided reliable
      information as to MJD being the direct cause of death. CONCLUSIONS: The fact that
      only nearly 40% of the patients with clinically confirmed MJD had a cause of
      death compatible with MJD precludes the use of cause of death as a means of
      identifying affected individuals in the Azorean MJD pedigrees.

PMID- 9779664
TI  - Characteristic magnetic resonance imaging findings in spinocerebellar ataxia 6.
AB  - OBJECTIVE: To clarify the characteristic magnetic resonance imaging (MRI)
      findings in patients with spinocerebellar ataxia 6 (SCA6) diagnosed by genetic
      analysis. PATIENTS AND METHODS: Using MRI, we examined 10 patients genetically
      diagnosed as having SCA6 and 40 control subjects. RESULTS: The mean (+/-SD) CAG
      repeat length in 10 patients with SCA6 was 22.9 +/- 1.3. There was a significant
      inverse correlation between the CAG repeat size and age at onset in the SCA6
      group (r = -0.86, P = .003). In patients with SCA6, the areas of the cerebellar
      vermis and hemispheres in sagittal MRI were significantly smaller than those in
      the control subjects. In transaxial MRI, the anteroposterior diameter of the pons
      and the diameter of the middle cerebellar peduncle were mildly decreased and the
      red nucleus was slightly atrophied in patients with SCA6. There was no
      significant difference in the diameter of the midbrain, medulla oblongata, fourth
      ventricle, superior cerebellar peduncles, dentate nucleus, or globus pallidus
      between the SCA6 and control groups. A high-signal intensity in the transverse
      pontine fibers was not observed in any of the patients with SCA6 on T2-weighted
      and/or proton-weighted axial MRI. CONCLUSIONS: The cerebellum and its afferent
      and efferent systems were affected in patients with SCA6. These results seem to
      distinguish the MRI findings of SCA6 from those of other forms of spinocerebellar
      ataxia.

PMID- 9779666
TI  - Reversal of vision metamorphopsia: clinical and anatomical characteristics.
AB  - BACKGROUND: Metamorphopsia is a visual illusion that distorts the size, shape, or
      inclination of objects. Reversal of vision metamorphopsia (RVM) is a rare
      transient form of metamorphopsia described as an upside-down, 180 degrees
      rotation of the visual field in the coronal plane. The pathophysiological
      characteristics of RVM remain unclear. DESIGN: Patients with RVM had a complete
      neurologic examination during or shortly after an episode of metamorphopsia, with
      particular emphasis on gaze disorders, visual fields, visually guided hand
      movements, and perceptual or cognitive deficits. Workup included imaging studies,
      visual field examinations, and brainstem auditory and visual evoked response.
      SETTING: Department of Neurology, Hadassah University Hospital, Hebrew University
      Hadassah Medical School, Jerusalem, Israel. PATIENTS: Six consecutive patients
      were evaluated from 1991 to 1996. RESULTS: Five patients had parieto-occipital
      brain insult sparing the primary visual cortex, and 3 also had evidence of a
      concomitant brainstem or cerebellar syndrome. One patient had pure brainstem
      syndrome underlying the RVM. Three patients had complete RVM as well as oblique
      RVM of less than 180 degrees. CONCLUSIONS: These cases imply a possible
      anatomical localization of the central integrator of visual extrapersonal
      orientation. Our observations suggest that a separate central mechanism of visual
      orientation might exist in each cerebral hemisphere and that occipital and
      parietal lesions that spare the optic radiations may account for the oblique and
      complete RVM. We postulate that failure to perceive space in an allocentric
      coordinate frame, particularly in the coronal roll plane, is potentially the
      critical event underlying RVM.

PMID- 9779665
TI  - Oculomotor phenotypes in autosomal dominant ataxias.
AB  - OBJECTIVE: To quantify the oculomotor features of the common spinocerebellar
      ataxia (SCA) syndromes. SETTING: University ataxia clinic. PATIENTS: Twenty
      probands with documented SCA mutations. METHODS: Electro-oculographic recordings
      of saccadic, smooth pursuit, optokinetic, vestibular, and visual-vestibular eye
      movements. RESULTS: Distinct phenotype and genotype patterns were identified with
      modest overlap between patterns. Slowing of saccade peak velocities occurred only
      in SCA1 and SCA2, being present in 100% of patients with SCA2. Impaired vestibulo
      ocular reflex gain occurred with SCA3 only. Patients with SCA6 had prominent
      deficits in smooth tracking but normal saccade velocities and vestibuloocular
      reflex gain. CONCLUSIONS: The oculomotor findings are consistent with pure
      cerebellar involvement in SCA6, pontine involvement in SCA1 and SCA2, and
      vestibular nerve or nuclei involvement in SCA3. These phenotypes can be useful
      for clinical diagnosis and for investigating the mechanism of system specificity
      with the SCA syndromes.

PMID- 9779667
TI  - Neurology was there in 1865.
AB  - In 1865 Americans saw the end of the Civil War, and their president, Abraham
      Lincoln, was assassinated. Slavery was abolished by the Thirteenth Amendment. The
      Atlantic cable linking Europe and the United States was completed. Bismarck and
      Napoleon III had a meeting resulting in Prussian supremacy in Germany. Lister had
      shown that antiseptic surgery was feasible and great surgical advances were made
      possible. Maxwell published his treatise defining the laws that related
      electricity to magnetism. Mendel's laws of heredity were formulated, and Pasteur
      saved the silk industry by curing silkworm disease. Alice in Wonderland was
      written by Lewis Carroll; Twain, Whitman, Homer, Inness, Wagner, and Rimsky
      Korsakov all added to our cultural heritage.

PMID- 9779668
TI  - Tissue-type plasminogen activator.

PMID- 9779669
TI  - Thrombolytic therapy in acute stroke.

PMID- 9779670
TI  - Benefits of home health care after inpatient rehabilitation for hip fracture:
      health service use by Medicare beneficiaries, 1987-1992.
AB  - OBJECTIVE: To examine the added benefit of home health services for elderly
      patients with hip fracture discharged home after inpatient rehabilitation. DATA:
      Medicare claims from 1% of 1986 beneficiaries followed until 1992. STUDY
      POPULATION: Persons hospitalized with hip fracture at 70 years or older who had
      no major Medicare claims during the year before hospitalization and who were
      discharged home after inpatient rehabilitation. OUTCOMES: Rehospitalization and
      any nonskilled nursing facility (non-SNF) nursing home admission during the 12
      months after hospital discharge. RESULTS: Patients who received additional home
      health services (27.2%) were less likely to be hospitalized than those who
      received rehabilitation only (31.1%); they were also less likely to have a non
      SNF nursing home admission (11.3% vs 23.3%), and more likely to survive the year
      with no subsequent Medicare claims (65.6% vs 55%). Propensity scores were used to
      adjust for nonrandom treatment selection in a Cox proportional hazards analysis
      showing that home health was associated with a significantly lower risk of
      nursing home admission (adjusted odds ratio = .42, 95% confidence interval .21
      .84), and hospitalization (adjusted odds ratio = .65, 95% confidence interval .26
      1.00). CONCLUSIONS: Studies of the relative effectiveness of post-acute services
      and postdischarge evaluations of inpatient rehabilitation should consider
      additional home care as a postacute service and examine optimal postacute
      treatment to minimize additional service use.

PMID- 9779671
TI  - Pre-AIDS physical disability: data from the AIDS Time-Oriented Health Outcome
      Study.
AB  - OBJECTIVE: To document the severity and correlates of perceived physical
      disability in a group of persons with HIV infection before an AIDS-defining
      illness, and to compare disability levels with a group of adults not infected
      with HIV. DESIGN: Observational cross-sectional study. SETTING: Community-based
      sample in California recruited through the AIDS Time-Oriented Health Outcome
      Study. PARTICIPANTS: Five hundred thirty-one asymptomatic and 345 symptomatic
      persons with HIV infection, primarily Caucasian, well-educated, homosexual and
      bisexual men. The control group consisted of 2,567 persons evaluated in the
      National Health and Nutrition Examination Survey and Epidemiologic Follow-up
      Study, a national probability sample of civilian, noninstitutionalized persons
      between ages 1 and 74 years living in the United States. MAIN OUTCOME MEASURE:
      Perceived physical disability measured by the HIV Health Assessment
      Questionnaire, a self-administered questionnaire that measures perceived
      disability in eight areas of mobility and activities of daily living. RESULTS:
      There were few significant differences between the asymptomatic and symptomatic
      groups. Total disability scores demonstrated a moderately strong relationship to
      number of symptoms, overall health status, employment, and Medical Outcomes Study
      HIV fatigue index (r = -.39 to .59; p < .001). With few exceptions, less than 10%
      of the cohort perceived limitations to any degree and no more than 2% reported
      being "unable to perform" in a given functional category. However, both groups
      demonstrated somewhat higher levels of physical dysfunction than an age-, race-,
      and education-matched comparison group of adults without HIV infection.
      CONCLUSIONS: Persons with HIV infection before an AIDS-defining illness
      demonstrate relatively low levels of physical dysfunction. When present, deficits
      tend to occur among instrumental activities of daily living. Despite the
      relatively low levels, perceived disability among the pre-AIDS sample is somewhat
      higher than that of the general population. Implications for functional
      assessment, disability screening, and future HIV disability research are
      discussed.

PMID- 9779672
TI  - Influence of urinary management on urologic complications in a cohort of spinal
      cord injury patients.
AB  - OBJECTIVE: To study urologic complications in patients with spinal cord injury
      (SCI) in relation to their bladder management. DESIGN AND SETTING: A cohort study
      of patients with SCI in a rehabilitation center. PARTICIPANTS: One hundred eighty
      two patients were studied; demographic data, disease characteristics, and
      urologic history were obtained for each. INTERVENTION: Patients responding to a
      questionnaire were given a clinical exam. Their medical records were reviewed,
      with particular attention given to the following urologic complications:
      lithiasis, urinary infections, orchiepididymitis, urethral trauma, vesicorenal
      reflux, and renal failure. RESULTS: Results are reported for 123 patients. Time
      since SCI was 8 years. Intermittent catheterization was the main method of
      bladder management. Only 32 patients had changed their method of vesical voiding.
      Urinary complications had developed in 75% of patients. The most common
      complication was urinary infection. Vesicoureteral reflux occurred in 26% of
      patients using percussion. Trauma related to catheterization was the main problem
      with intermittent catheterization, responsible for a high rate of
      orchiepididymitis. CONCLUSION: Intermittent catheterization is the most-used
      method of bladder management, but with a nonnegligible rate of urethral trauma in
      men. Percussion and Crede maneuver appear to be acceptable techniques of bladder
      management if the patient is closely monitored.

PMID- 9779673
TI  - Functional changes in back muscle activity correlate with pain intensity and
      prediction of low back pain during pregnancy.
AB  - OBJECTIVE: To assess low back pain (LBP) intensity and subjective disability
      during pregnancy and compare the pain scores with lumbar motion patterns. DESIGN:
      A prospective study of pregnant back pain sufferers and healthy controls.
      SETTING: Kuopio University Hospital, Kuopio, Finland. PARTICIPANTS: Study group
      consisted of 32 pregnant women with LBP; control group consisted of 21 healthy
      pregnant women. MAIN OUTCOME MEASURES: Back pain intensity was assessed by visual
      analog scale (VAS), and subjective disability index was measured by Oswestry Low
      Back Disability Questionnaire, at 20 and 36 weeks of pregnancy. Back muscle
      activities were recorded by surface electromyography, and movement sensors were
      used to detect lumbar motion. RESULTS: In the study group current pain scores
      (VAS) at first and last trimester correlated strongly (r = .82, p < .00). Pain
      scores correlated with body weight at the first trimester (r = .54, p = .003) and
      at the last trimester (r = .67, p < .00). Significant correlation was noted
      between current pain intensity and back muscle activity level during forward body
      flexion at first trimester (r = .704, p < .00). Back muscle activity during
      bending measured at first trimester significantly correlated with pain intensity
      at last trimester (r = .703, p < .00). Back muscle activity during the first
      trimester of pregnancy had a negative correlation with current (r = -.57, p =
      .002) and later subjective disability index (r = -.42, p = .02). It correlated
      inversely (r = -.54, p = .003) with pain score at last trimester of pregnancy,
      ie, the lower the back muscle activity at the beginning of pregnancy, the more
      pain and disability throughout pregnancy. In the control group, three women
      developed LBP and disability feelings during pregnancy. They had increased muscle
      activity during flexion at delivery, ie, disturbed flexion relaxation.
      CONCLUSIONS: Prepregnancy LBP predicts renewed pain during pregnancy, and
      dysfunction of back muscles has been established in LBP. In this study,
      disturbance in the relaxation of the back muscles was linearly related to
      current, and also to later, pain scores. In addition, back muscle activity level
      was inversely related to the disability index. For the first time, it has been
      shown prospectively that the function pattern of back extensors seems to predict,
      and is related to, future back pain. Simple function testing is promising and
      might be valuable in identifying mothers with a high risk of pregnancy-related
      back pain and in directing preventive intervention to high risk women by making
      them aware of self-treatment methods.

PMID- 9779674
TI  - Measuring progress and outcome in community rehabilitation after brain injury
      with a new assessment instrument--the BICRO-39 scales. Brain Injury Community
      Rehabilitation Outcome.
AB  - OBJECTIVE: Construction and validation of a new instrument, the Brain Injury
      Community Rehabilitation Outcome scales, to assess problems experienced by brain
      injured patients living in the community. DESIGN: Seventy-six items describing
      aspects of personal and social functioning were generated. Two hundred thirty
      five patients and/or their carers (separately) rated the items on 6-point scales,
      and patients retrospectively rated their functioning before injury. Seven scales
      were derived from factor analysis; one was included a priori. Thirty-nine items
      with high factor loadings were retained. Test-retest reliability, interrater
      reliability, and construct validity were examined in subsamples. SETTING:
      Patients were recruited from four centers: two community-based teams, a day
      patient clinic, and an outpatient clinic. PATIENTS: Of the patients, 127 had
      traumatic brain injury, 72 had cerebrovascular accidents, 15 had multiple
      sclerosis, and 21 had acquired brain injury of other origins. Mean time since
      brain injury was 2.6 years; mean age was 43 years; 164 were men and 71 were
      women. RESULTS: All scales showed good test-retest reliability, and agreement
      between patient and carer ratings was moderate to high. They showed predicted
      moderate correlations with other relevant scales. Postinjury scores differed
      significantly from preinjury scores, and 6 of the 8 scales showed change over a
      period of recovery/rehabilitation. CONCLUSIONS: The scales appear reliable and
      easy to complete. They may have utility as quantitative measures of outcome for
      clinical and treatment evaluations.

PMID- 9779675
TI  - Scapula winger's brace: a case series on the management of long thoracic nerve
      palsy.
AB  - OBJECTIVE: To evaluate the clinical utility of a new scapula winger's brace.
      DESIGN: A case series. SETTING: A tertiary military clinic serving a young
      population. PARTICIPANTS: Fourteen patients referred to the clinic for thoracic
      nerve palsy of a least 3 months' duration. OUTCOME MEASURES: Manual muscle tests
      with and without the brace and patients' compliance/satisfaction with brace as
      measured by personal interview during follow-up. RESULTS: Muscle strength
      increased by one grade with brace application; patients who maintained compliance
      (n = 6) recovered their brace-free shoulder flexion strength and/or had reduced
      pain at the last follow-up (1 to 7 months after brace). All patients reported a
      subjective feeling of increased shoulder flexion strength and decreased pain with
      brace application. CONCLUSION: The scapula winger's brace is a useful tool for
      physiatrists in the management of scapular winging secondary to long thoracic
      nerve palsy. Additional studies are needed to confirm the conclusion that the
      device's benefits derive from proprioceptive feedback that prevents muscle
      overuse or overstretch and from its transfer of contralateral shoulder
      protraction force to the affected scapula.

PMID- 9779676
TI  - Interrater reliability of the Functional Assessment Measure in a brain injury
      rehabilitation program.
AB  - OBJECTIVE: To examine the interrater reliability and completion time of the
      Functional Assessment Measure, which is the Functional Independence Measure (FIM)
      plus additional items (FIM+FAM). DESIGN: Interrater reliability study. SETTING:
      Inpatient rehabilitation units of a postacute care brain injury rehabilitation
      program. PATIENTS: A convenience sample of 53 extremely severely impaired adult
      survivors of traumatic brain injuries (40 men, 13 women, mean age 38yrs). MAIN
      OUTCOME MEASURES: Treatment team members' ratings of the 30 FIM +FAM items, and
      time taken to complete the FIM+FAM. RESULTS: Intraclass Correlation Coefficients
      (ICCs) were within the good to excellent range (ICC > .60) for 29 of 30 items and
      for all subscales except psychosocial adjustment. Higher mean ICC values were
      obtained for motor domain items than for cognitive/psychosocial domain items.
      Treatment teams became progressively faster over a 12-week period in completing
      the FIM+FAM. The generally good to excellent range interrater reliability found
      in this study helps support the use of the FIM+FAM in rehabilitation settings.
      Further support was obtained for the finding that motor items are more reliable
      than cognitive and psychosocial items. Administration of the FIM+FAM can be done
      in a timely manner in a rehabilitation setting.

PMID- 9779677
TI  - Postrehabilitation outcomes after spinal cord injury caused by firearms and motor
      vehicle crash among ethnically diverse groups.
AB  - OBJECTIVES: To determine the differential effects of impairment, disability,
      etiology, and selected preinjury and social factors on medical complications,
      medical resources use, and handicap after rehabilitation for spinal cord injury
      (SCI). DESIGN: Survey including interview and medical record review. SETTING:
      Model SCI Care System centered at an urban, public medical center. PARTICIPANTS:
      A volunteer convenience sample of 164 men, ages 18 to 35yrs at injury, with SCI
      caused by firearms or motor vehicle crash. MAIN OUTCOME MEASURES: Mean numbers of
      documented complications, pressure sore episodes, nonroutine clinic visits,
      postrehabilitation hospitalization days per year, assessment by Functional
      Independence Measure (FIM), and total score on the Craig Handicap Assessment and
      Reporting Technique (CHART). RESULTS: Significant factors for postrehabilitation
      complications were discharge FIM (p < .001) and injury duration (p = .046); for
      pressure ulcer episodes, they were injury completeness (p < .001), drug abuse
      following injury (p = .005), and ethnicity (p = .043); for average annual
      nonroutine clinic visits, they were complications (p < .001), pressure ulcer
      episodes (p < .001), duration of injury (p = .001), and pain (p = .052); for
      hospitalization, they were pressure ulcer episodes (p < .001) and complications
      (p = .043); for CHART scores, they were discharge FIM (p < .001), preinjury
      education (p < .001), hospitalization (p = .007), chronic pain (p = .01), longest
      time at one job (p = .02), completeness of injury (p = .042), and preinjury
      employment (p = .049). CONCLUSIONS: Disability is the most important factor in
      postrehabilitation outcomes for SCI, followed by injury completeness, which is
      also associated with multiple outcomes. Postinjury but not preinjury drug abuse
      is adversely associated with outcomes. Etiology and ethnicity are not important
      determinates of outcome.

PMID- 9779678
TI  - Braking electric-powered wheelchairs: effect of braking method, seatbelt, and
      legrests.
AB  - OBJECTIVE: To examine the influence of three electric-powered wheelchair braking
      conditions and four wheelchair seating conditions on electric-powered wheelchair
      motion and Hybrid II test dummy motion. This study provides quantitative
      information related to assessing the safety of electric-powered wheelchair
      driving. DESIGN: Rehabilitation engineering comparison and ANSI/ RESNA standards
      testing. Convenience sample of eight different electric-powered wheelchairs.
      Within-chair comparisons were conducted. INTERVENTION: Electric-powered
      wheelchairs were compared under three braking scenarios (joystick release,
      joystick reverse, power-off) and four seating conditions (seatbelt and legrests,
      seatbelt and no legrests, no seatbelt but legrests, no seatbelt and no legrests).
      SETTING: A rehabilitation engineering center. MAIN OUTCOME MEASURES: The braking
      distance, braking time, and braking accelerations for electric-powered
      wheelchairs during three braking scenarios; trunk motion, head motion, and trunk
      angular acceleration during three braking scenarios and four seating conditions;
      and number of falls from the wheelchairs for three braking scenarios and four
      seating conditions. RESULTS: Significant differences (p < .05) were found in
      braking distance, braking time, and braking acceleration when comparing the
      joystick release and joystick reverse scenarios with the power-off scenario. The
      mean braking distance was shortest with the power-off braking scenario (.89m),
      whereas it was longest when the joystick was released (1.66m). Significant
      differences (p < .05) in head displacement and trunk angular displacement were
      observed among braking conditions and between seating conditions. There were also
      significant differences (p = .0011) among braking conditions for maximum trunk
      angular acceleration. The Hybrid II test dummy fell from the wheelchairs with
      highest frequency when there were no legrests and no seatbelt used. CONCLUSION:
      The results of this study indicate that use of a seatbelt when driving an
      electric-powered wheelchair reduces the risk of falling from a wheelchair.
      Furthermore, the use of legrests can reduce the risk of injury to the wheelchair
      driver. This study shows that the most abrupt braking occurs when deactivating
      the power switch.

PMID- 9779679
TI  - Aftereffects of resisted muscle contractions on the accuracy of joint position
      sense in elite male athletes.
AB  - OBJECTIVE: To examine the effects of quadriceps and hamstring muscle strength
      testing on the results of subsequent knee joint position sense tests. DESIGN: A
      case-control study of 40 elite male athletes divided equally into two groups,
      experimental and control. METHODS: Both groups underwent position sense tests of
      both knees, with eyes closed, with isometric maintenance of the knee in each test
      position, return of the limb to the starting position, then active replication of
      the perceived test position using the same limb. In the experimental group, joint
      sense testing commenced 5 to 25 min after strength testing of quadriceps and
      hamstring muscle strength in both legs using maximum isokinetic contractions at
      plateau speeds of 60 degrees/sec and 120 degrees/sec. The control group did not
      undergo pretest muscle strength testing. RESULTS: The difference in the mean
      absolute (signless) and relative (signed) position sense errors between the
      experimental and control groups was 0.8 degrees and 1.4 degrees, respectively.
      The difference between the standard deviation of the relative errors was 1.2
      degrees. These results were not statistically significant (analysis of variance p
      = .24, .12, and .13, respectively). CONCLUSION: In elite male athletes knee joint
      position sense is unaffected by nonfatiguing strength tests conducted 5 to 25 min
      before position sense testing.

PMID- 9779680
TI  - Ischemic stroke: relation of age, lesion location, and initial neurologic deficit
      to functional outcome.
AB  - OBJECTIVE: Establish the relation between age, gender, initial neurologic
      deficit, stroke location, prior stroke, hemisphere of stroke, and functional
      outcome in ischemic stroke. DESIGN: Single group, multivariate, repeated measures
      design with 327 persons having ischemic stroke recruited from 20 participating
      centers. SETTING: Twenty European stroke centers. PATIENTS: Consecutive
      admissions of men and women between the ages of 40 and 85 yrs with a hemispheric
      stroke caused by middle cerebral artery ischemia and a Unified Neurological
      Stroke Scale score of 5 to 24. INTERVENTIONS: Inpatients enrolled in the trial
      received traditional rehabilitation therapies including physical therapy,
      occupational therapy, and speech therapy when appropriate. MAIN OUTCOME MEASURES:
      Barthel Index computed at 7 to 10 days and 3 months poststroke. RESULTS: Positive
      functional outcomes were significantly related to the absence of prior strokes, a
      younger age, a less severe initial neurologic deficit, stroke involving cortical
      structures, and dominant (left hemisphere) lesions. CONCLUSIONS: Despite some
      inconsistencies in existing literature, standardized prospective examination of
      outcome after stroke clearly demonstrated the effect of age, initial severity of
      stroke, and lesion location as predictors of functional outcome.

PMID- 9779681
TI  - Rebox effect on exercise-induced acute inflammation in human muscle.
AB  - OBJECTIVE: To evaluate the effect of Rebox stimulation on an experimental model
      of soft tissue inflammation. DESIGN: Randomized trial, partially blinded,
      comparing a control group with active and placebo Rebox. SUBJECTS: Thirty healthy
      volunteers, 15 women. METHODS: Delayed onset muscle soreness was induced in
      biceps brachii muscle by weighted eccentric exercise. Rebox stimulation was
      applied daily for 3 days using a negatively charged probe electrode, at pulse
      duration of 100 microsec, amplitude of 160 microamp, and frequency of 3000 Hz.
      OUTCOME MEASURES: DAILY ratings of pain by visual analogue scale (VAS), and
      tenderness by pressure-pain threshold (PPT) and pressure-pain tolerance (PT).
      RESULTS: Significant increases in VAS and decreases in PPT and PT were found at
      24 and 48 hours. There were no differences between groups. CONCLUSION: Rebox had
      no effect on this experimental model of soft tissue injury.

PMID- 9779682
TI  - Serial fiberoptic endoscopic swallowing evaluations in the management of patients
      with dysphagia.
AB  - OBJECTIVE: To determine whether serial fiberoptic endoscopic evaluation of
      swallowing (FEES) can be used successfully and efficiently in deciding to change
      a patient's feeding status from nonoral (NPO) to oral (PO) with no adverse health
      outcome. DESIGN: A prospective, consecutive, cohort study. SETTING: Inpatient
      population of a tertiary-care university teaching hospital. SUBJECTS: Thirty-two
      adults were recruited from a cohort of 400 consecutive subjects who participated
      in a previous dysphagia study. INTERVENTION: Serial FEES was performed 3 to 6
      times in each subject to detect objectively pharyngeal phase dysphagia,
      aspiration, and aspiration risk and to provide information for recommendations
      regarding oral feeding status and therapeutic intervention. The number of FEES
      was based on the subject's medical status, evidence of dysphagia, and clinical
      judgement. MAIN OUTCOME MEASURES: Identification of pharyngeal phase dysphagia,
      aspiration, and aspiration risk, and recommendations for initial feeding status,
      when to resume oral feeding, and what bolus consistencies to use for optimal
      swallowing success. RESULTS: In all subjects, serial FEES detected pharyngeal
      phase dysphagia, aspiration, and aspiration risk and enabled determination of
      initial feeding status (NPO or PO), when to resume successful oral feeding, and
      what bolus consistencies to use for optimal swallowing success. Specifically, 15
      of 32 (47%) subjects received FEES 3 to 5 times within only 6 to 22 days. Timely
      serial FEES allowed 22 of 32 (69%) subjects to resume an oral diet as early and
      safely as possible. CONCLUSIONS: No subject who resumed an oral diet based on
      results of FEES developed an aspiration pneumonia. Serial FEES, therefore,
      enabled feeding status to be successful and efficiently changed from NPO to PO
      with no adverse health outcome. FEES was an efficient procedure with regard to
      appointment scheduling, transportation, patient issues, and personnel
      requirements.

PMID- 9779683
TI  - Assessing the knowledge of future internists and gynecologists in caring for a
      woman with tetraplegia.
AB  - OBJECTIVE: To assess the knowledge base and comfort level of potential physician
      "gatekeepers" when treating women with spinal cord injuries. Residents with at
      least 1 year of training in either internal medicine (IM) or obstetrics and
      gynecology (Ob/Gyn) from a large academic urban medical center were surveyed.
      STUDY DESIGN: This study used a written questionnaire that included a case
      scenario of a young woman with C6 tetraplegia who presented to her primary care
      physician for a routine visit. Information about the patient from her history and
      physical and laboratory exams was presented in stages, followed by open-ended
      queries to elicit information about the residents' problem-solving processes and
      management strategies. RESULTS: Thirty-eight percent (30 of 79) of the IM
      residents and 64% (14 of 22) of the Ob/Gyn residents completed the questionnaire.
      Significant deficits in knowledge about physical accessibility, spasticity
      management, and potential disability-related medical complications in pregnancy
      were found. More Ob/Gyn residents were aware of the risk of autonomic
      hyperreflexia than IM residents, whereas the IM residents demonstrated greater
      awareness of neurogenic bladder and skin problems. Both groups indicated they
      were not very comfortable in managing the patient's care. CONCLUSIONS: The
      results raise concern about the adequacy of the training of primary care
      physicians to meet the needs of people with severe disabilities.

PMID- 9779684
TI  - Rehabilitation staff perceptions of characteristics of geriatric rehabilitation
      patients.
AB  - OBJECTIVE: To determine if professionals treating older rehabilitation patients
      regarded them as having different characteristics than younger rehabilitation
      patients, to derive factors from these perceptions, and to examine the impact of
      the discipline of the professional and other factors on these perceptions.
      DESIGN: Rehabilitation professionals at a random sample of facilities accredited
      by the Commission on Accreditation of Rehabilitation Facilities were surveyed to
      determine their level of agreement with 60 items addressing characteristics of
      older rehabilitation patients. The items were derived from focus groups with
      rehabilitation staff members. PARTICIPANTS: One thousand sixty-three
      rehabilitation professionals from nine disciplines (nursing, occupational
      therapy, physiatry, physical therapy, psychology, social work, speech pathology,
      therapeutic recreation, and vocational counseling) responded to the questionnaire
      and were included in the study. RESULTS: There was a wide range of agreement
      levels across the 60 items (range of median agreement, 12.7% to 93.5%). Factor
      analysis resulted in six categories of perceptions regarding older rehabilitation
      patients: (1) physical limitations, (2) motivational deficits, (3) psychological
      distress/need for support, (4) maturity and positive coping skills, (5) need for
      privacy/decreased adaptability, and (6) discharge complications. Significant
      differences across disciplines were found for five of six factors. Nurses agreed
      more strongly with the negative psychological factors (2, 3, and 5) compared to
      physical therapists, psychologists, and social workers. Physicians scored
      significantly higher than two other disciplines on the physical limitations
      factor. These differences may be related to the distinct role each discipline
      plays in the rehabilitation process. Older professionals also scored higher on
      four factors, likely because of personal rather than professional experience with
      aging. CONCLUSIONS: Treating professionals recognize differences between younger
      and older rehabilitation patients. Many of these perceived differences can be
      viewed as variables that require more effort and skill on the part of the
      treating professional. The training of rehabilitation professionals needs to
      better prepare individuals from all disciplines to adapt to age-specific
      differences.

PMID- 9779685
TI  - Carpal tunnel syndrome in pregnancy: frequency, severity, and prognosis.
AB  - OBJECTIVE: To determine the frequency, severity, prognosis, and patterns of
      carpal tunnel syndrome (CTS) in pregnancy. DESIGN: Descriptive retrospective
      chart review using the Rochester Epidemiology Project medical record diagnostic
      indexing system to identify patients with new CTS occurring during pregnancy from
      1987 to 1992 at our institution. SETTING: Obstetrical practice, where two thirds
      of pregnant women in the county receive primary obstetrical care. PATIENTS: Women
      pregnant during 1987 to 1992 who had a new diagnosis of CTS. Women with
      pregnancies at other dates or women who had CTS with onset before or after
      pregnancy were excluded. OUTCOME MEASURES: Age, underlying medical problems,
      gestation interval, weight gain, number of pregnancies, presenting symptoms,
      onset and duration of symptoms before diagnosis, trimester of CTS diagnosis,
      treatment and response, and results of electrophysiologic studies are described.
      RESULTS: Of 10,873 pregnant patients receiving antenatal care for 14,579
      pregnancies, 50 (.34%) fulfilled the inclusion criteria. Their mean age was 30.5
      +/- 4.0 yrs. Twelve patients (24%) were primigravid. Mean weight gain was 12.1 +/
      5.7 kg. CTS was diagnosed most frequently during the third trimester (n = 25,
      50%). Symptom onset, when recorded, occurred with even distribution during each
      trimester: first, n = 11 (32%); second, n = 11 (32%); third, n = 12 (35%). For 37
      patients in whom symptom duration was recorded, duration before diagnosis was 9.3
      +/- 9.0 weeks. Paresthesia (88%) was most often bilateral (68%), and 67% of
      patients had pain. The Tinel sign was present over the median nerve at the wrist
      in 95%. Only nine patients had nerve conduction studies performed. During
      pregnancy, 37 women were treated nonsurgically with wrist orthoses, steroid
      injections, or both. Of treated patients for whom follow-up data were available,
      25 of 26 improved, and 4 of 26 required surgery. Thirteen women had no treatment
      during pregnancy; three underwent surgery in the postpartum period. All 7 women
      in whom conservative treatment failed who underwent surgery had resolution of
      symptoms. CONCLUSION: These results represent the frequency and patterns of
      clinically significant CTS in a large population of pregnant women. CTS severe
      enough to warrant treatment occurs infrequently in pregnancy and generally
      resolves spontaneously postpartum or responds to conservative treatment.

PMID- 9779686
TI  - On-road assessment of driving competence after brain impairment: review of
      current practice and recommendations for a standardized examination.
AB  - OBJECTIVE: To examine the approaches to on-road assessment of driver competence
      in persons with brain impairment. Items examined were procedures,
      standardization, scoring methods, equipment requirements, and determination of
      fitness to drive. DATA SOURCES: All studies identified through citation or
      Medline search. STUDY SELECTION: The studies reviewed were those published from
      1971 to the present that examined driving competence after brain impairment, as
      measured by a driving test. DATA EXTRACTION: A qualitative review of published
      studies reporting methodologies and authors' conclusions abstracted from sourced
      publications. DATA SYNTHESIS: Off-road driving assessments examine proficiency in
      operating a motor vehicle, but not ability to drive in traffic or accurate
      prediction of safe driving. On-road driving assessments have been used to examine
      the predictive validity of other driving assessment methods or the driving
      performance of subjects with brain impairment. Determining a subject's competence
      to drive is frequently a subjective evaluation. With a standardized driving test,
      a significant correlation between the objective driving score and the rater's
      global evaluation of fitness has been reported. CONCLUSION: Closed-course, off
      road driving tests are recommended for examining vehicle operation skills and
      readiness for in-traffic evaluation only. This allows practice with any vehicle
      adaptations before on-road evaluation and identification of clients who are
      unsafe to proceed on-road. A practical driving test in traffic, with standardized
      route and driving maneuvers, is recommended for determining driver competence.
      Scoring of driving performance should be standardized, reliable, and specific, to
      identify deficient driving skills that may be amenable to training. Driving
      performance should be evaluated according to predefined criteria, and the
      judgment regarding competence should be closely related to this objective
      measure.

PMID- 9779687
TI  - Symptomatic Helicobacter pylori infection in a neurorehabilitation population.
AB  - Helicobacter pylori infection has been associated with acute and chronic
      gastritis, peptic ulcer disease, hypertension, and possibly gastric carcinoma and
      coronary artery disease. The prevalence of H pylori infection is more than 50% in
      people older than 60 years; however, the prevalence is not known in patients with
      traumatic brain injury (TBI) or cerebrovascular accidents who are treated in
      inpatient rehabilitation services. This report describes 10 symptomatic patients
      with TBI and strokes who were diagnosed with and treated for H pylori infection
      after transfer to a neurorehabilitation unit during a 12-month period. Physicians
      who treat patients with TBI and stroke need to be aware of the possible high
      prevalence of H pylori infection in their patients. The authors recommend H
      pylori screening for symptomatic patients in neurorehabilitation units and
      providing definitive treatment to prevent recurrent gastrointestinal bleeding,
      peptic ulcer disease, and gastritis.

PMID- 9779688
TI  - Intracranial tumor masquerading as cervical radiculopathy: a case study.
AB  - Physicians who treat musculoskeletal and neurologic disorders often treat
      patients who have paresthesias or weakness of a single extremity. Although the
      diagnosis is often straightforward, cases that are atypical in nature may pose a
      diagnostic dilemma. This report describes the case of a middle-aged man with
      symptoms indicative of, though not classic for, a cervical radiculopathy. An
      extensive investigation was unremarkable and only the eventual rapid progression
      of symptoms led to the diagnosis of a glioblastoma multiforme. Although this is a
      deadly form of brain cancer, early recognition provides the best chance for a
      prolonged and greater quality of life.

PMID- 9779689
TI  - Management of focal dystonia of the extensor hallucis longus muscle with
      botulinum toxin injection: a case report.
AB  - Recently botulinum toxin has been used with increasing frequency as a safe and
      effective treatment for many previously refractory conditions associated with
      excessive muscle activity. The indications for use of botulinum toxin injection
      continue to expand. This report describes the case of an 83-year-old woman with a
      history of diabetes mellitus and lumbar spinal stenosis who developed a severe
      focal dystonia of the left great toe, such that the toe maintained the extended
      position. Functionally, the resultant deformity prevented the patient from
      wearing shoes. In addition, the patient had significant pain in the left great
      toe. Under needle electromyographic localization, 50 units of botulinum toxin
      were injected into the left extensor hallucis longus muscle. Two weeks after the
      injection the patient was symptom free and could place her left foot into a shoe.
      Seven months later, she remained symptom free. This case illustrates that
      localized injection of botulinum toxin to a specific lower limb muscle can
      effectively result in decreased muscle activity and functional improvement.

PMID- 9779690
TI  - Ballroom dancing and cervical radiculopathy: a case report.
AB  - Dance injuries associated with cervical radiculopathy have not been described in
      the literature. This report describes the case of an international-style ballroom
      dancer who developed a cervical radiculopathy as a result of frequent lateral
      rotation and hyperextension of the cervical spine during dancing. The patient's
      symptoms and signs suggestive of a left C7 radiculopathy were confirmed and
      documented by both magnetic resonance imaging and electrodiagnostic testing. The
      patient was treated conservatively with activity modification, nonsteroidal anti
      inflammatory drugs, and alternative medicine approaches, including herbs and
      acupuncture. Her neck pain and cervical radicular symptoms declined in severity,
      but continued even 4 1/2 months after the onset of her symptoms. She did not wish
      to try steroids either through an oral or epidural route and refused surgical
      intervention. This case report illustrates an unconventional manner in which a
      left cervical radiculopathy was clinically produced. The neck motions and
      positions of frequent hyperextension and lateral rotation demonstrated by this
      ballroom dancer simulated a pattern and sequence of movements that promoted the
      development of signs and symptoms of a left cervical radiculopathy.

PMID- 9779691
TI  - A new dynamic triceps-driven orthosis (DTDO): achieving elbow flexion in patients
      with C5 deficits.
AB  - This report describes a unique orthosis designed to assist activities of daily
      living for a patient with severe proximal upper limb weakness caused by traumatic
      central cord syndrome. The orthosis-the dynamic triceps-driven orthosis (DTDO)
      provides elbow flexion using contralateral elbow extension to move a cable
      threaded across the shoulders and wrist cuffs bilaterally. The device is a
      simple, inexpensive design that can be reproduced by any orthotist. The DTDO has
      been used successfully for other patients with severe weakness in C5- and C6
      innervated muscles.

PMID- 9779692
TI  - Managed care and people with disabilities: framing the issues.
AB  - A physical, cognitive, or mental disability presents significant challenges to an
      individual in gaining access to a coordinated program of preventive, primary, and
      secondary health care services. This article describes the health care needs of
      people with disabilities and discusses how the financial incentives in managed
      care may threaten access to the health care services they need to maintain their
      health and functional independence. We argue that despite the shortcomings of
      present models, managed care has the potential to improve the health care of
      people with disabilities. Moreover, as health plans become increasingly
      accountable to consumers (and begin to compete on the basis of quality), they
      will not be able to ignore the distinct health care needs of people with
      disabilities.

PMID- 9779693
TI  - Methadone in cancer pain management: individualize dose and titrate to effect.

PMID- 9779694
TI  - Switching from morphine to oral methadone in treating cancer pain: what is the
      equianalgesic dose ratio?
AB  - PURPOSE: To define the dose ratio between morphine and methadone in relation to
      the previous morphine dose and the number of days needed to achieve the same
      level of analgesia in a group of patients with advanced cancer with pain who
      switched from morphine to oral methadone. PATIENTS AND METHODS: A cross-sectional
      prospective study of 38 consecutive cancer patients who switched from morphine to
      oral methadone was performed. The intensity of pain before, during, and after the
      switching period was assessed through a four-point verbal Likert scale. The
      relationship between previous morphine dose and the final equianalgesic methadone
      dose, dose ratio between morphine and methadone, and the number of days required
      to achieve equianalgesia have been examined by means of Pearson's correlation
      coefficient, scatter plots, and Cuzick's test for trend respectively. RESULTS:
      Before the switch, the median oral equivalent daily dose of morphine was 145
      mg/d; after the switch, the median equianalgesic oral methadone dose was 21 mg/d.
      A median time of 3 days (range, 1 to 7 days) was necessary to achieve the
      equianalgesia with oral methadone; the lower the preswitching morphine dose, the
      fewer days necessary to achieve equianalgesia with oral methadone (P < .001).
      Dose ratios ranged from 2.5:1 to 14.3:1 (median, 7.75:1), which indicated that,
      in most cases, the dose ratio was much higher than that suggested by the
      published equianalgesic tables. A strong linear positive relationship between
      morphine and methadone equianalgesic doses was obtained (Pearson's correlation
      coefficient, 0.91). The dose ratio increased with the increase of the previous
      morphine dose with a much higher increase at low morphine doses. CONCLUSION: The
      results of our study confirm that methadone is a potent opioid, more potent than
      believed. Caution is recommended when switching from any opioid to methadone,
      especially in patients who are tolerant to high doses of opioids.

PMID- 9779696
TI  - Comparison of controlled-release and immediate-release oxycodone tablets in
      patients with cancer pain.
AB  - PURPOSE: This study compared the clinical efficacy of oxycodone hydrochloride
      controlled-release (CR) tablets administered every 12 hours with immediate
      release (IR) oxycodone tablets administered four times daily in patients with
      cancer-related pain. PATIENTS AND METHODS: Cancer patients who required therapy
      for moderate to severe pain were randomized to CR oxycodone every 12 hours (n=81)
      or IR oxycodone four times daily (n=83) for 5 days in a multicenter, double-blind
      study. Pain intensity was assessed four times daily (categorical scale of none,
      slight, moderate, and severe); acceptability of therapy was assessed twice daily
      (categorical scale of very poor, poor, fair, good, and excellent). RESULTS: Pain
      intensity remained slight during the study, with mean oxycodone doses of 114 mg/d
      (range, 20 to 400 mg/d) for CR and 127 mg/d (range, 40 to 640 mg/d) for IR.
      Acceptability of therapy was fair to good with both treatments. While standard
      conversion ratios provided an acceptable dose for many patients, a protocol
      amendment that allowed initial titration and use of rescue medication reduced the
      discontinuation rate for lack of acceptable pain control (from 34% to 4% with CR
      and from 31% to 19% with IR before and after amendment, respectively) without
      increasing the discontinuation rate for adverse events (from 8% to 7% with CR and
      from 13% to 11% with IR). Fewer adverse events were reported with CR (109) than
      with IR (186) oxycodone (P=.006). CONCLUSION: CR oxycodone every 12 hours was as
      effective as IR oxycodone four times daily in managing moderate to severe cancer
      related pain and was associated with fewer reports of adverse events.

PMID- 9779695
TI  - Randomized, double-blind, cross-over trial comparing safety and efficacy of oral
      controlled-release oxycodone with controlled-release morphine in patients with
      cancer pain.
AB  - PURPOSE: Use of oxycodone for chronic cancer pain has been hampered by its short
      elimination half-life. This study was designed to compare the efficacy and safety
      of controlled-release formulations of oxycodone and morphine for cancer pain.
      PATIENTS AND METHODS: Thirty-two adult patients with cancer pain and a > or = 3
      day history of stable analgesia with oral opioids provided written informed
      consent and were randomized to controlled-release oxycodone or controlled-release
      morphine for 7 days. To blind the study using available tablet strengths, the
      dose ratio of oxycodone to morphine was set at 1:1.5. On day 8, patients were
      crossed over to the alternate drug for 7 days. Pain intensity was assessed using
      a visual analog scale (VAS 0 to 100 mm) and a categorical scale (CAT 0 to 4).
      Side effects were assessed using a checklist (four-point categorical severity)
      and a nondirected questionnaire. Patients and investigators made blinded global
      ratings of efficacy and treatment preference. RESULTS: Twenty-three patients
      completed the study (10 men, 13 women). The VAS and CAT scores were (mean+/-SD)
      23+/-21 and 1.2+/-0.8 on controlled-release oxycodone, and 24+/-20 (P=.43) and
      1.3+/-0.7 (P=.36) on controlled-release morphine. No period or carryover effect
      was detected. There were no significant differences in adverse effects (P=.40) or
      ratings of efficacy and preference. The median oxycodone/morphine dose ratio was
      1.5 and the maximum was 2.3. CONCLUSION: Controlled-release oxycodone is as safe
      and effective as controlled-release morphine in the treatment of cancer pain.

PMID- 9779697
TI  - Dose-titration, multicenter study of oral transmucosal fentanyl citrate for the
      treatment of breakthrough pain in cancer patients using transdermal fentanyl for
      persistent pain.
AB  - PURPOSE: Supplemental, "as-needed," administration of an opioid is a common
      approach to the problem of breakthrough pain in cancer patients. Oral
      transmucosal fentanyl citrate (OTFC) is undergoing investigation as a new
      treatment for breakthrough pain. The primary purpose of the study was to
      demonstrate that a single-unit dose of OTFC can safely and effectively treat
      breakthrough pain. A secondary goal was to determine appropriate dosing
      guidelines. PATIENTS AND METHODS: This was a multicenter, randomized, double
      blind, dose-titration study in 62 adult cancer patients using transdermal
      fentanyl for persistent pain. Consenting patients provided 2 days of baseline
      data to evaluate the performance of their usual breakthrough pain medication.
      Patients then randomly received 200 microg or 400 microg OTFC in double-blind
      fashion. (Patients were always assigned, rather than randomized, to 200 microg if
      400 microg represented > 20% of around-the-clock medication.) Pain intensity
      (PI), pain relief (PR), and global satisfaction scores were recorded. OTFC was
      then titrated until the patient received adequate PR for each episode using one
      OTFC unit. Orders to titrate up were ignored one third of the time to improve the
      blind. Two days of baseline data were compared with 2 days of OTFC data after
      titration identified an effective dose of OTFC. RESULTS: Most patients (76%)
      found a safe and effective dose of OTFC. There was no meaningful relationship
      between the around-the-clock opioid regimen and the effective dose of OTFC. In
      open-label comparisons, OTFC produced a faster onset of relief and a greater
      degree of PR than patients' usual breakthrough medication. Somnolence, nausea,
      and dizziness were the most common side effects associated with OTFC. CONCLUSION:
      Most patients find a single OTFC dosage that adequately treats breakthrough pain.
      The optimal dose is found by titration and is not predicted by around-the-clock
      dose of opioids.

PMID- 9779698
TI  - Maximum-tolerated dose, toxicity, and efficacy of (131)I-Lym-1 antibody for
      fractionated radioimmunotherapy of non-Hodgkin's lymphoma.
AB  - PURPOSE: Lym-1, a monoclonal antibody that preferentially targets malignant
      lymphocytes, has induced remissions in patients with non-Hodgkin's lymphoma (NHL)
      when labeled with iodine 131 ((131)I). Based on the strategy of fractionating the
      total dose, this study was designed to define the maximum-tolerated dose (MTD)
      and efficacy of the first two, of a maximum of four, doses of (131)I-Lym-1 given
      4 weeks apart. Additionally, toxicity and radiation dosimetry were assessed.
      MATERIALS AND METHODS: Twenty patients with advanced NHL entered the study a
      total of 21 times. Thirteen (62%) of the 21 entries had diffuse large-cell
      histologies. All patients had disease resistant to standard therapy and had
      received a mean of four chemotherapy regimens. (131)I-Lym-1 was given after Lym-1
      and (131)I was escalated in cohorts of patients from 40 to 100 mCi (1.5 to 3.7
      GBq)/m2 body surface area. RESULTS: Mean radiation dose to the bone marrow from
      body and blood (131)I was 0.34 (range, 0. 1 6 to 0.63) rad/mCi (0.09 mGy/MBq;
      range, 0.04 to 0.17 mGy/ MBq). Dose-limiting toxicity was grade 3 to 4
      thrombocytopenia with an MTD of 100 mCi/m2 (3.7 GBq/m2) for each of the first two
      doses of (131)I-Lym-1 given 4 weeks apart. Nonhematologic toxicities did not
      exceed grade 2 except for one instance of grade 3 hypotension. Ten (71 %) of 14
      entries who received at least two doses of (131)I-Lym-1 therapy and 11 (52%) of
      21 total entries responded. Seven of the responses were complete, with a mean
      duration of 14 months. All three entries in the 100 mCi/m2 (3.7 MBq/m2) cohort
      had complete remissions (CRs). All responders had at least a partial remission
      (PR) after the first therapy dose of (131)I-Lym-1. CONCLUSION: (131)I-Lym-1
      induced durable remissions in patients with NHL resistant to chemotherapy and was
      associated with acceptable toxicity. The nonmyeloablative MTD for each of the
      first two doses of (131)I-Lym-1 was 100 mCi/m2 (total, 200 mCi/m2) (3.7 GBq/m2;
      total, 7.4 GBq/m2).

PMID- 9779699
TI  - CAMPATH-1H monoclonal antibody in therapy for previously treated low-grade non
      Hodgkin's lymphomas: a phase II multicenter study. European Study Group of
      CAMPATH-1H Treatment in Low-Grade Non-Hodgkin's Lymphoma.
AB  - PURPOSE: CAMPATH-1H is a human immunoglobulin G1 (IgG1) anti-CD52 monoclonal
      antibody (MAb) that binds to nearly all B-cell and T-cell lymphomas. We report
      here the results of a multicenter phase II trial of CAMPATH-1H in patients with
      advanced, low-grade non-Hodgkin's lymphoma (NHL) who were previously treated with
      chemotherapy. PATIENTS AND METHODS: Fifty patients who had relapsed (n=25) after
      or were resistant (n = 25) to chemotherapy were treated with CAMPATH-1H 30 mg
      administered as a 2-hour intravenous (i.v.) infusion three times weekly for a
      maximum period of 12 weeks. RESULTS: Six patients (14%) with B-cell lymphomas
      achieved a partial remission (PR). Patients with mycosis fungoides appeared to
      respond more frequently (50%; four of eight patients, which included two complete
      remissions [CRs]). Lymphoma cells were rapidly eliminated from blood in 16 of 17
      patients (94%). CR in the bone marrow was obtained in 32% of the patients.
      Lymphoma skin lesions disappeared completely in four of 10 patients and partial
      regression was obtained in three patients. Lymphadenopathy and splenomegaly were
      normalized in only 5% and 15% of patients, respectively. Lymphopenia (< 0.5 x
      10(9)/L) occurred in all patients. World Health Organization (WHO) grade IV
      neutropenia occurred in 14 patients (28%). Opportunistic infections were
      diagnosed in seven patients and nine patients had bacterial septicemia. Death
      related to infectious complications occurred in three patients. CONCLUSION:
      CAMPATH-1H had a significant but limited activity in patients with advanced,
      heavily pretreated NHL. The most pronounced effects were noted in the blood and
      bone marrow and in patients with mycosis fungoides. The risk for serious
      infectious complications needs to be considered for severely ill patients who are
      evaluated for CAMPATH-1H treatment.

PMID- 9779700
TI  - Time to relapse has prognostic value in patients with aggressive lymphoma
      enrolled onto the Parma trial.
AB  - PURPOSE: The purpose of this study was to investigate the prognostic value of
      time to relapse in 188 adult patients with intermediate- or high-grade non
      Hodgkin's lymphoma (NHL) included on the Parma trial at the time of their first
      relapse. PATIENTS AND METHODS: The median follow-up of these patients is 102
      months after registration onto the Parma study. Time to relapse was calculated
      from initial diagnosis, and a cutoff of 12 months was used to separate 77
      patients defined as early relapse from 111 patients defined as late relapse.
      RESULTS: Patients with early and late relapses had significantly different
      overall response rates to salvage therapy with two courses of dexamethasone, high
      dose cytarabine, and cisplatin (DHAP; 40% v 69%; P=.00007) and different 8-year
      survival rates (13% v 29%; P=.00001). Features at relapse with a negative
      prognostic value in univariate analysis were higher than normal lactic
      dehydrogenase (LDH) levels, tumor size greater than 5 cm, Ann Arbor stages III to
      IV, and Karnofsky score less than 80%. Therefore, multivariate analyses were
      performed. Time to relapse (P=.001) and LDH levels at relapse (P=.003) had
      independent prognostic value, whereas tumor size did not reach statistical
      significance in the logistic model that predicted overall response after two
      courses of DHAP. The study of prognostic factors for overall survival (OS) and
      progression-free survival (PFS) confirmed the prognostic value of time to relapse
      (P < .0001 for OS and P=.005 for PFS) independent of response or treatment after
      two courses of DHAP. CONCLUSION: Time to relapse may be used to stratify patients
      at time of first relapse of intermediate to high-grade non-Hodgkin's lymphoma.

PMID- 9779702
TI  - Suppression of cytogenetic clonal evolution with interferon alfa therapy in
      patients with Philadelphia chromosome-positive chronic myelogenous leukemia.
AB  - PURPOSE: To investigate whether cytogenetic clonal evolution can be suppressed
      with interferon alfa (IFN-alpha) therapy in patients with chronic myelogenous
      leukemia (CML). PATIENTS AND METHODS: Ninety patients with CML and cytogenetic
      clonal evolution who received IFN-alpha-based regimens were analyzed. Clonal
      evolution was defined as the presence of karyotypic abnormalities in addition to
      the Philadelphia (Ph) chromosome. Patients were evaluated for the suppression of
      cytogenetic clonal evolution after therapy, the cytogenetic response, and
      survival. RESULTS: The median age of the population was 39 years (range, 15 to 70
      years), median time from diagnosis to clonal evolution 14 months (range, 0 to 145
      months), and median percentage of abnormal metaphases 18% (range, 4% to 100%).
      Fifty six patients (62%) achieved some suppression of cytogenetic clonal
      evolution; in 41 patients (46%), the suppression was complete. The overall median
      survival was 51 months, with 43% alive at 5 years. Patients who achieved a
      complete suppression of cytogenetic clonal evolution had a median survival of 66
      months, with 51% alive at 5 years. Characteristics associated with a better
      response include a lower percentage of abnormal metaphases, time to cytogenetic
      clonal evolution of 24 months or less, and absence of other features of
      accelerated disease. A prognostic classification for cytogenetic clonal evolution
      defined three groups with complete response (CR) rates of 85%, 34%, and 0% (P <
      .0001) and median survival times of 58, 31, and 30 months, respectively (P=.02).
      CONCLUSION: Patients with cytogenetic clonal evolution can respond to IFN-alpha
      therapy, and this response is associated with longer survival. A previously
      described prognostic model separates patients into subsets with different
      probabilities of response to IFN-alpha and survival.

PMID- 9779701
TI  - Follow-up of relapsed B-cell lymphoma patients treated with iodine-131-labeled
      anti-CD20 antibody and autologous stem-cell rescue.
AB  - PURPOSE: Radioimmunotherapy (RIT) is a promising treatment approach for B-cell
      lymphomas. This is our first opportunity to report long-term follow-up data and
      late toxicities in 29 patients treated with myeloablative doses of iodine-131
      anti-CD20 antibody (anti-B1) and autologous stem-cell rescue. PATIENTS AND
      METHODS: Trace-labeled biodistribution studies first determined the ability to
      deliver higher absorbed radiation doses to tumor sites than to lung, liver, or
      kidney at varying amounts of anti-B1 protein (0.35, 1.7, or 7 mg/kg). Twenty-nine
      patients received therapeutic infusions of single-agent (131)I-anti-B1, given at
      the protein dose found optimal in the biodistribution study, labeled with amounts
      of (131)I (280 to 785 mCi [10.4 to 29.0 GBq]) calculated to deliver specific
      absorbed radiation doses to the normal organs, followed by autologous stem-cell
      support. RESULTS: Major responses occurred in 25 patients (86%), with 23 complete
      responses (CRs; 79%). The nonhematopoietic dose-limiting toxicity was reversible
      cardiopulmonary insufficiency, which occurred in two patients at RIT doses that
      delivered > or = 27 Gy to the lungs. With a median follow-up time of 42 months,
      the estimated overall and progression-free survival rates are 68% and 42%,
      respectively. Currently, 14 of 29 patients remain in unmaintained remissions that
      range from 27+ to 87+ months after RIT. Late toxicities have been uncommon except
      for elevated thyroid-stimulating hormone (TSH) levels found in approximately 60%
      of the subjects. Two patients developed second malignancies, but none have
      developed myelodysplasia (MDS). CONCLUSION: Myeloablative (131)I-anti-B1 RIT is
      relatively well tolerated when given with autologous stem-cell support and often
      results in prolonged remission durations with few late toxicities.

PMID- 9779703
TI  - Prognostic significance of MYCN oncogene expression in childhood neuroblastoma.
AB  - PURPOSE: To assess the significance of MYCN gene expression as a prognostic
      factor in patients with neuroblastoma of various ages, and to determine whether
      it can predict for outcome independently of MYCN gene amplification. PATIENTS AND
      METHODS: The level of MYCN gene expression in 60 specimens of primary untreated
      neuroblastoma was determined by reverse-transcriptase polymerase chain reaction
      (RT-PCR) analysis. RESULTS: High levels of MYCN gene expression were associated
      with advanced tumor stage (P=.0005), with the presence of MYCN gene amplification
      (P < .0001), but not with older age at diagnosis. Among patients who lacked MYCN
      gene amplification, the levels of MYCN gene expression were significantly greater
      in the tumors of infants compared with those of older children (P < .0005). High
      MYCN expression was strongly associated with reduced survival and event-free
      survival in the overall study population (P < .005), and also in the subset of
      patients aged older than 1 year at diagnosis (P < .001). In contrast, MYCN
      expression did not appear to be predictive of outcome in infants. After
      adjustment for the effect of MYCN amplification, high levels of MYCN expression
      retained significant prognostic value for poor survival (relative hazards, 30.3;
      P=.003) in children aged older than 12 months at diagnosis. CONCLUSION: High MYCN
      gene expression is strongly predictive of poor outcome in older children with
      neuroblastoma, but not in infants. The findings help explain the controversy in
      the literature about the prognostic value of MYCN gene expression and highlight
      the different biology of neuroblastoma that presents in infants and older
      children.

PMID- 9779704
TI  - High-dose melphalan, etoposide, and carboplatin followed by autologous stem-cell
      rescue in pediatric high-risk recurrent Wilms' tumor: a French Society of
      Pediatric Oncology study.
AB  - PURPOSE: The three-drug combination of melphalan (M), etoposide (E), and
      carboplatin (C) followed by autologous stem-cell (ASC) rescue has been evaluated
      prospectively by the French Society of Pediatric Oncology (SFOP) in pediatric
      high-risk recurrent (HRR) Wilms' tumor (WT) patients with chemotherapy-responsive
      disease. PATIENTS AND METHODS: From October 1988 to October 1994, 29 patients
      with HRR WT were treated in nine SFOP centers. Two additional patients with stage
      IV anaplastic WT were consolidated in first complete response (CR) with the same
      regimen and have been studied separately. The regimen consisted of M 180 mg/m2
      for 1 day, E 200 mg/m2/d for 5 days, and C at a daily targeted area under the
      concentration-time curve (AUC) of 4 mg x min/mL for 5 days. ASCs were reinfused
      48 hours after M. RESULTS: Twelve of 28 assessable patients with HRR WT are still
      in continuous CR at a median of 48.5 months (range, 36 to 96) after
      consolidation. Disease-free survival (DFS) and overall survival (OS) estimated by
      the Kaplan-Meier method at 3 years were 50%+/-17% and 60%+/-18%, respectively.
      Sixteen patients relapsed at a median of 8.5 months (range, 3 to 53) after
      consolidation. Toxicity data are available in 31 grafted patients. Grade III and
      IV toxicities included hematologic side effects (n=31), hemorrhage (n=8),
      mucositis (n=24), diarrhea (n=12), renal disorders (n=8), and pneumonitis (n=3).
      CONCLUSION: The adverse prognostic factors (APF) used to select patients for this
      dose-intensive chemotherapy define children with very-poor-risk recurrent WT.
      Despite high treatment-related toxicity, about half of these patients remain
      disease-free at 3 years. Patient outcome is statistically better when high-dose
      chemotherapy (HDCT) is performed as early as the second CR or partial response
      (PR). Novel therapeutic approaches with innovative preparative regimens are
      warranted for the remaining high-risk patients.

PMID- 9779705
TI  - Phase I and pharmacologic study of continuous infusion topotecan in combination
      with cisplatin in patients with advanced cancer: a Cancer and LeukemiaGroup B
      study.
AB  - PURPOSE: Preclinical and clinical data suggest that topotecan may be more
      effective, and perhaps less toxic, when administered as a continuous intravenous
      infusion (CIVI). A previous Cancer and Leukemia Group B (CALGB) trial of
      topotecan, given on a daily bolus schedule in combination with cisplatin,
      produced more hematologic toxicity than expected with either drug alone.
      Therefore, we designed this phase I trial to define the dose-limiting toxicities
      (DLTs) and the recommended phase II doses of cisplatin in combination with
      topotecan administered as a CIVI. Population pharmacodynamic models for the
      combination also were investigated. PATIENTS AND METHODS: Patients with advanced
      solid tumors and a maximum of one prior chemotherapy regimen for metastatic
      disease were eligible if they had a performance status of 0 to 1 and adequate
      renal, hepatic, and bone marrow function. Prior treatment with camptothecins or
      platinum compounds and prior pelvic irradiation were not allowed. The initial
      schedule consisted of a fixed dose of topotecan 0.4 mg/m2/d administered as a
      CIVI for 21 days and escalating doses of cisplatin administered on days 1, 8, and
      15 of a 28-day schedule, until the maximum tolerated dose (MTD) was achieved.
      After severe hematologic toxicity was observed in the first two patients, the
      topotecan infusion was shortened to 14 days, and the total dose of cisplatin was
      administered on day 1 in all subsequent patients. After the MTD was defined, that
      cohort was expanded to include a total of 12 assessable patients. Hematopoietic
      growth factors were not allowed. For the pharmacologic studies, total topotecan
      plasma concentrations were measured by high-pressure liquid chromatography (HPLC)
      during infusion on days 3, 8, and 11 on the first cycle, and the median steady
      state concentration (Tss) was determined. Platinum plasma concentrations on day 3
      were measured by atomic absorption spectrometry. RESULTS: Of the 32 patients
      enrolled, 28 were assessable for toxicity and 24 for response. The primary
      toxicity was hematologic, with both neutropenia and thrombocytopenia being dose
      limiting. The MTD of cisplatin was 75 mg/m2 on day 1 in combination with
      topotecan 0.4 mg/m2/d for 14 days. At this dose level, three of a total of 12
      assessable patients had DLT. The pharmacodynamic relationship between Tss and the
      absolute neutrophil count at the nadir (ANCn) was described by the following
      equation: log10 (ANCn)=4.23 - 0.47 x Tss - 0.01 x cisplatin dose (P < .0001;
      R2=0.64). The substitution of platinum concentration for cisplatin dose in this
      model did not result in a significant improvement. Three patients had a partial
      response: one with duodenal carcinoma; a second with small-cell lung cancer; and
      a third with melanoma. CONCLUSION: Cisplatin can be given safely in combination
      with CIVI topotecan. However, toxicity was still substantial. Based on the
      current results and our previous trial of this combination, we conclude that,
      when combined with cisplatin, CIVI topotecan does not seem to be advantageous
      compared with the more traditional daily bolus schedule.

PMID- 9779706
TI  - Correlation of tumor O6 methylguanine-DNA methyltransferase levels with survival
      of malignant astrocytoma patients treated with bis-chloroethylnitrosourea: a
      Southwest Oncology Group study.
AB  - PURPOSE: Prior studies show that increased levels of the DNA repair protein O6
      methylguanine-DNA methyltransferase (MGMT), also referred to as O6-alkylguanine
      DNA alkyltransferase (AGT) correlate with the resistance of glioma cell lines to
      nitrosoureas. The observed nitrosourea sensitivity of MGMT-deficient lines
      (methyl excision repair negative [MER-]) and those repair-proficient lines
      pretreated with MGMT-specific inhibitors (eg, O6 benzylguanine) has raised the
      possibility that tumor MGMT levels may be an important predictor of survival in
      patients with gliomas. PATIENTS AND METHODS: We correlated the MGMT level in
      malignant astrocytoma tissues, obtained from patients treated with radiotherapy
      and bis-chloroethylnitrosourea (BCNU) on a prior prospective trial (Southwest
      Oncology Group [SWOG] 8737), with overall and failure-free survival. RESULTS: Of
      64 assessable patients with malignant astrocytoma (63% glioblastoma, 37%
      anaplastic astrocytoma), 64% had high (> 60,000 molecules/nucleus) MGMT levels.
      The overall median survival for patients with high versus low MGMT levels was 8
      and 29 months, respectively (P=.0002), and median failure-free survival 3 and 6
      months, respectively (P=.008). Subset analysis by histology (high v low MGMT
      levels) for anaplastic astrocytoma was 14 versus 62 months (n=24) and for
      glioblastoma was 7 versus 12 months (n=40). The overall hazards ratio (risk for
      death) for high versus low MGMT levels was 3.41; in young patients, the hazards
      ratio was higher (age 18 to 40 years, 4.19; age 41 to 60 years, 3.08) but became
      equal by MGMT level at age older than 60 years (1.11). Multivariate analysis
      showed that MGMT was independent of other known prognostic factors (age,
      performance status, histology). CONCLUSION: The MGMT level in tumor tissue
      specimens may be a predictive marker of survival in patients with malignant
      astrocytoma that is independent of other previously described prognostic
      variables.

PMID- 9779707
TI  - Multiinstitutional phase II trial of paclitaxel, carboplatin, and concurrent
      radiation therapy for locally advanced non-small-cell lung cancer.
AB  - PURPOSE: Combined modality therapy for non-small-cell lung cancer (NSCLC) has
      produced promising results. A multiinstitutional phase II clinical trial was
      conducted to evaluate the activity and toxicity of paclitaxel, carboplatin, and
      concurrent radiation therapy on patients with locally advanced NSCLC. PATIENTS
      AND METHODS: Forty previously untreated patients with inoperable locally advanced
      NSCLC entered onto a phase II study from March 1995 to December 1996. On an
      outpatient basis for 7 weeks, patients received paclitaxel 50 mg/m2 weekly over 1
      hour; carboplatin at (area under the curve) AUC 2 weekly; and radiation therapy
      of 66 Gy in 33 fractions. After chemoradiation therapy, patients received an
      additional two cycles of paclitaxel 200 mg/m2 over 3 hours and carboplatin at AUC
      6 every 3 weeks. RESULTS: Thirty-nine patients were eligible for the study. The
      survival rates at 12 months were 56.3%, and at 24 months, 38.3%, with a median
      overall survival of 20.5 months. The progression-free survival rates at 12 months
      were 43.6%, and at 24 months, 34.7%, with a median progression-free survival of
      9.0 months. Two patients did not receive more than 2 weeks of concurrent
      chemoradiotherapy and were not assessable for toxicity and response. The overall
      response rate (partial plus complete response) of 37 assessable patients was
      75.7%. The major toxicity was esophagitis. Seventeen patients (46%) developed
      grade 3 or 4 esophagitis. However, only two patients developed late esophageal
      toxicity with stricture at 3 and 6 months posttreatment. CONCLUSION: Combined
      modality therapy with paclitaxel, carboplatin, and radiation is a promising
      treatment for locally advanced NSCLC that has a high response rate and acceptable
      toxicity and survival rates. A randomized trial will be necessary to fully
      evaluate the usefulness of these findings.

PMID- 9779708
TI  - Abbreviated treatment for elderly, infirm, or noncompliant patients with limited
      stage small-cell lung cancer.
AB  - PURPOSE: To evaluate the efficacy of an abbreviated treatment plan consisting of
      two cycles of chemotherapy plus thoracic irradiation in a population of limited
      stage small-cell lung cancer (LSCLC) patients who were elderly, infirm, or
      noncompliant with standard-duration therapy. PATIENTS AND METHODS: Fifty-five
      LSCLC patients (median age, 73) were treated with one cycle of cyclophosphamide,
      doxorubicin, and vincristine (CAV) followed 3 weeks later by one cycle of
      etoposide and cisplatin (EP). Both regimens were administered at conventional
      full dose. Thoracic irradiation (20 to 30 Gy) was delivered concurrently with EP.
      RESULTS: Complete response occurred in 28 patients (51%) and partial response in
      21 (38%). The median survival time was 54 weeks; the 2-year survival rate was 28%
      and the actual 5-year survival rate was 18%. Three patients died of toxicity.
      CONCLUSION: Elderly, infirm, or noncompliant LSCLC patients who are unable to
      receive standard-duration chemotherapy may have useful palliation and potential
      for long-term survival with abbreviated chemotherapy (two cycles) and thoracic
      irradiation.

PMID- 9779709
TI  - Combination of irinotecan and etoposide for treatment of refractory or relapsed
      small-cell lung cancer.
AB  - PURPOSE: To determine the response rate, survival, and toxicity of irinotecan
      (CPT-11), a topoisomerase I inhibitor, combined with etoposide, a topoisomerase
      II inhibitor, in refractory or relapsed small-cell lung cancer (SCLC). PATIENTS
      AND METHODS: Twenty-five patients with refractory or relapsed SCLC were entered
      onto the trial. All 25 patients had been pretreated with some form of cisplatin
      based combination chemotherapy and had also received previous etoposide- or
      anthracyclinecontaining chemotherapy. The median time off chemotherapy was 6.7
      months (range, 0.9 to 23.5). Patients were treated at 4-week intervals using CPT
      11 (a starting dose of 70 mg/m2 intravenously on days 1, 8, and 15) plus
      etoposide (80 mg/m2 intravenously on days 1 to 3), with a subsequent dose based
      on toxicity. In addition, recombinant human granulocyte colony-stimulating factor
      (rhG-CSF; 2 microg/kg/d) was given from day 4 to day 21, except on the days of
      CPT-11 administration. RESULTS: All patients were assessable for toxicity and
      survival. Twenty-four patients were assessable for response. There were 14
      partial responses (PRs) and three complete responses (CRs), for an overall
      response rate of 71% (95% confidence interval, 53% to 89%). The median response
      duration was 4.6 months. Median survival was 271 days. Major toxicities were
      myelosuppression (predominantly leukopenia) and diarrhea. Grade 3 to 4
      neutropenia and thrombocytopenia occurred in 56% and 20% of patients,
      respectively. Grade 3 to 4 diarrhea was observed in 4%. There was one treatment
      related death due to severe myelosuppression. CONCLUSION: A combination of CPT-11
      and etoposide with rhG-CSF support is an active therapy against refractory or
      relapsed SCLC and deserves to be studied more extensively in a phase III trial.

PMID- 9779710
TI  - Randomized trial of recombinant human interleukin-3 versus placebo in prevention
      of bone marrow depression during first-line chemotherapy for ovarian carcinoma.
AB  - PURPOSE: To determine whether recombinant human interleukin-3 (rhIL-3) reduces
      bone marrow depression and improves chemotherapeutic schedule adherence in
      ovarian cancer patients receiving first-line combination chemotherapy. PATIENTS
      AND METHODS: In a randomized multicenter study, 185 patients received carboplatin
      (dose based on projected area under the concentration-time curve [AUC]=4) and
      cyclophosphamide (750 mg/m2) day 1, every 3 weeks for six cycles. Patients were
      randomized to receive rhIL-3 (5 microg/kg) or placebo once daily subcutaneously
      on days 3 to 12. RESULTS: Adherence to chemotherapeutic regimen, mean
      chemotherapy cycle length, tumor response rate, and median survival at 24 months
      did not differ between groups. The number of side effects-primarily allergic
      reactions, flu-like symptoms and fever-were higher in the rhIL-3 group, which
      resulted in 21 discontinuations compared with one in the placebo group. Compared
      with placebo, the rhIL-3 group had higher platelet counts day 1 of cycles 2 to 6.
      The number of patients with World Health Organization (WHO) grade IV
      thrombocytopenia or number of platelet transfusions did not differ. Leukocyte
      counts differed only in cycles 1 and 2 between groups. The leukocyte nadir
      occurred earlier in the rhIL-3 (day 12) than in the placebo group (day 15,
      P=.006). Leukocytes and neutrophils were only higher in the rhIL-3 group day 1 of
      cycle 2. In cycles 4 and 5, more patients with WHO grade IV neutropenia received
      rhIL-3 (P < .005). Eosinophil counts were higher day 1 of cycles 2 to 6 in the
      rhIL-3 group (P < .0001). CONCLUSION: rhIL-3 had stimulatory hematopoietic
      effects. This did not result either in reduction of platelet transfusions or in
      improvement of chemotherapeutic schedule adherence. There were more side effects
      in the rhIL-3 group than in the placebo group. rhIL-3 at 5 microg/kg/d is,
      therefore, not of clinical benefit in this chemotherapeutic regimen.

PMID- 9779711
TI  - Topotecan for the treatment of advanced epithelial ovarian cancer: an open-label
      phase II study in patients treated after prior chemotherapy that contained
      cisplatin or carboplatin and paclitaxel.
AB  - PURPOSE: Topotecan, a topoisomerase I inhibitor, was evaluated in a multicenter,
      phase II study of women with epithelial ovarian carcinoma who relapsed after one
      or two prior regimens that included platinum and paclitaxel. PATIENTS AND
      METHODS: Topotecan 1.5 mg/m2 daily was administered as a 30-minute infusion for 5
      consecutive days on a 21-day cycle. Eligibility criteria included bidimensionally
      measurable disease, Eastern Cooperative Oncology Group performance status of 2 or
      less, and adequate bone marrow, liver, and renal function. Efficacy was assessed
      by independent radiologic review. RESULTS: One hundred thirty-nine patients were
      treated; 81% were platinum resistant. Sixty-two patients had received one prior
      regimen and 77 patients had received two prior regimens. Nine patients were not
      assessable for response; however, all patients were included in the response
      analysis. The overall response rate was 13.7%; 12.4% in platinum-resistant and
      19.2% in platinum-sensitive patients. Stable disease lasted at least 8 weeks in
      27.3% of the patients. The median duration of response and time to progression
      were 18.1 and 12.1 weeks, respectively. The median survival was 47.0 weeks. Grade
      4 neutropenia occurred in 82% of the patients (34% of the courses) and
      thrombocytopenia in 30% of the patients (9% of the courses). Infectious
      complications occurred in 6% of the courses. Nonhematologic toxicities were mild.
      There were no drug-related toxic deaths. CONCLUSION: As a single agent, topotecan
      has modest activity in women with advanced epithelial ovarian carcinoma who have
      progressed or not responded after one or two prior regimens with platinum and
      paclitaxel. Further investigation of combination regimens is indicated in the
      primary therapy for ovarian cancer based on the mechanism of action and
      tolerability.

PMID- 9779712
TI  - Dose-dense therapy with weekly 1-hour paclitaxel infusions in the treatment of
      metastatic breast cancer.
AB  - PURPOSE: To evaluate the efficacy and toxicity of paclitaxel administered as a 1
      hour infusion on weekly basis, without interruption, to patients with metastatic
      breast cancer who had received prior therapy. PATIENTS AND METHODS: Thirty
      patients with metastatic breast cancer received sustained weekly paclitaxel
      therapy at an initial dose of 100 mg/m2 until disease progression. Prior therapy
      included adjuvant only (n=17), metastatic only (n=7), or both (n=6). Eighteen
      patients had received prior anthracycline therapy, 12 of whom had demonstrated
      progression of disease within 12 months of it. All patients were assessable for
      efficacy; 29 patients were assessable for toxicity. Pharmacokinetic studies of
      paclitaxel were also performed. RESULTS: A total of 469 weekly paclitaxel
      infusions were administered to 30 patients (median, 14 infusions/patient). The
      median delivered dose-intensity was 91 mg/m2/wk (range, 80 to 108). The overall
      response rate was 53% (95% confidence interval [CI], 34% to 72%), with 10%
      complete responses (CRs) and 43% partial responses (PRs). Median response
      duration was 7.5 months (range, 2 to 11+). Responses were observed in nine of 18
      (50%) patients with prior anthracycline therapy, including six of 12 (50%) with
      disease progression on anthracycline within 1 year (three of four within 6
      months). Therapy was well tolerated and remarkable for a lack of overall and
      cumulative myelosuppression. Grade 3/4 neutropenia occurred in four patients;
      febrile neutropenia was not observed. Peripheral neuropathy prohibited dose
      escalation above 100 mg/m2, and grade 3 neuropathy was observed in two of 21
      patients at < or = 100 mg/m2. CONCLUSION: Weekly paclitaxel therapy is active and
      well tolerated in patients with metastatic breast cancer. Weekly therapy should
      be considered as a current clinical option for these patients and should be
      incorporated into future comparative clinical trials.

PMID- 9779713
TI  - A phase II study of docetaxel in patients with paclitaxel-resistant metastatic
      breast cancer.
AB  - PURPOSE: To evaluate the efficacy and safety of docetaxel in patients with
      paclitaxel-resistant metastatic breast cancer (MBC). PATIENTS AND METHODS:
      Docetaxel (100 mg/m2) was administered every 3 weeks to 46 patients registered at
      four centers. Patients had previously received < or = two chemotherapy regimens
      for MBC. All patients had progressive disease while receiving paclitaxel therapy.
      Treatment was repeated until there was evidence of disease progression or for a
      maximum of three cycles after best response. RESULTS: Objective responses were
      seen in eight of 44 assessable patients (18.1%; 95% confidence interval [CI],
      6.7% to 29.5%). Seven patients had partial responses and one patient responded
      completely. Response rates were not significantly different by previously
      received paclitaxel dose or resistance. No responses were seen in 12 patients who
      had previously received paclitaxel by 24-hour infusion, but the response rate in
      32 patients who had received paclitaxel by 1- to 3-hour infusion was 25%. The
      median response duration was 29 weeks and the median time to disease progression
      was 10 weeks. Median survival was 10.5 months. Clinically significant (severe)
      adverse events included neutropenic fever (24% of patients), asthenia (22%),
      infection (13%), stomatitis (9%), neurosensory changes (7%), myalgia (7%), and
      diarrhea (7%). CONCLUSION: Docetaxel is active in patients with paclitaxel
      resistant breast cancer, particularly in those who failed to respond to brief
      infusions of paclitaxel. Response rates were comparable to or better than those
      seen with other therapies for patients with paclitaxel-resistant MBC. This
      confirms preclinical studies, which indicated only partial cross-resistance
      between paclitaxel and docetaxel.

PMID- 9779714
TI  - Phase II trial of liposomal daunorubicin in the treatment of AIDS-related
      pulmonary Kaposi's sarcoma.
AB  - PURPOSE: Kaposi's sarcoma (KS) is the most common tumor in patients with AIDS and
      can be fatal in patients with lung involvement. Systemic chemotherapy is the most
      effective treatment for pulmonary KS. We thus conducted this study to determine
      the efficacy of liposomal daunorubicin in the treatment of patients with
      pulmonary KS. METHODS: Patients with biopsy-proven, symptomatic pulmonary KS were
      accrued. Liposomal daunorubicin was given at a dose of 60 mg/m2 intravenously
      every 2 weeks. Response was monitored by chest radiographs, pulmonary function
      tests, arterial blood gases, and grading of pulmonary symptoms. RESULTS: Fifty
      three male patients were accrued. The median CD4+ lymphocyte count was 13/microL
      (range, 0 to 200); 70% reported a prior AIDS-defining opportunistic infection.
      All patients were symptomatic, with cough reported in all patients, shortness of
      breath in 94%, and hemoptysis in 55%. The mean study entry diffusing capacity of
      carbon monoxide (DLCO) was 58.5% (percent of predicted). The median dose of
      liposomal daunorubicin delivered was 360 mg/m2 (range, 60 to 1,380). More than
      75% of patients had complete or partial resolution of baseline pulmonary
      symptoms. Complete or partial improvement in DLCO was observed in 22%; complete
      or partial resolution of radiographic abnormalities was reported in 32%. The most
      common treatment-related toxicity was neutropenia, which occurred in 85%. There
      were no instances of cardiac toxicity observed, even at high cumulative doses.
      CONCLUSION: Liposomal daunorubicin at 60 mg/m2 is safe and active in patients
      with pulmonary KS. Trials combining liposomal daunorubicin with other active
      agents in KS should be considered.

PMID- 9779715
TI  - Detection of bone metastases in breast cancer by 18FDG PET: differing metabolic
      activity in osteoblastic and osteolytic lesions.
AB  - PURPOSE: 99mTechnetium methylene diphosphonate (99mTc MDP) bone scintigraphy is
      currently the method of choice for the detection of bone metastases, but 18F
      fluoro-deoxy-D-glucose positron emission tomography (18FDG PET) offers superior
      spatial resolution and improved sensitivity. We have compared 18FDG PET with
      99mTc MDP bone scintigraphy in patients with skeletal metastases from breast
      cancer and have analyzed the data in subgroups based on radiographic
      characteristics of lesions. PATIENTS AND METHODS: Twenty-three women with breast
      cancer and confirmed bone metastases were studied with both 99mTC MDP bone
      scintigraphy and 18FDG PET, and the number of lesions detected and the
      quantitation of uptake (standardized uptake values [SUVs]) of 18FDG in osteolytic
      and osteoblastic metastases were compared. Survival was compared for both lytic
      and blastic bone metastases and for patients with high and low accumulation of
      18FDG. RESULTS: 18FDG PET detected more lesions than 99mTc MDP scintigraphy
      (mean, 14.1 and 7.8 lesions, respectively; P < .01). However, 18FDG detected
      fewer bone metastases compared with 99mTc MDP scintigraphy in a subgroup of
      patients with osteoblastic disease (P < .05). Higher SUVs were observed for
      osteolytic than osteoblastic disease (mean, 6.77 and 0.95, respectively; P <
      .01). Survival was lower in patients with osteolytic disease compared with the
      remainder (P=.01). A difference in survival was not found for those patients with
      high SUVs (> 3.6; P=.4). CONCLUSION: 18FDG PET is superior to bone scintigraphy
      in the detection of osteolytic breast cancer metastases, which led to a poorer
      prognosis. In contrast, osteoblastic metastases show lower metabolic activity and
      are frequently undetectable by PET. The biologic explanation for this observation
      remains to be elucidated.

PMID- 9779716
TI  - Predictors of improved outcome for patients with localized prostate cancer
      treated with neoadjuvant androgen ablation therapy and three-dimensional
      conformal radiotherapy.
AB  - PURPOSE: To identify prognostic variables that predict for improved biochemical
      and local control outcome in patients with localized prostatic cancer treated
      with neoadjuvant androgen deprivation (NAAD) and three-dimensional conformal
      radiotherapy (3D-CRT). MATERIALS AND METHODS: Between 1989 and 1995, 213 patients
      with localized prostate cancer were treated with a 3-month course of NAAD that
      consisted of leuprolide acetate and flutamide before 3D-CRT. The purpose of NAAD
      in these patients was to reduce the preradiotherapy target volume so as to
      decrease the dose delivered to adjacent normal tissues and thereby minimize the
      risk of morbidity from high-dose radiotherapy. The median pretreatment prostate
      specific antigen (PSA) level was 15.3 ng/mL (range, 1 to 560 ng/mL). The median
      3D-CRT dose was 75.6 Gy (range, 64.8 to 81 Gy), and the median follow-up time was
      3 years (range, 1 to 7 years). RESULTS: The significant predictors for improved
      outcome as identified in a multivariate analysis included pretreatment PSA level
      < or = 10.0 ng/mL(P < .00), NAAD-induced preradiotherapy PSA nadir < or = 0.5
      ng/mL (P < .001), and clinical stage < or = T2c (P < .04). The 5-year PSA relapse
      free survival rates were 93%, 60%, and 40% for patients with pretreatment PSA
      levels < or = 10 ng/mL, 10 to 20 ng/mL, and greater than 20 ng/mL, respectively
      (P < .001). Patients with preradiotherapy nadir levels < or = 0.5 ng/mL after 3
      months of NAAD experienced a 5-year PSA relapse-free survival rate of 74%, as
      compared with 40% for patients with higher nadir levels (P < .001). The incidence
      of a positive biopsy among 34 patients pretreated with androgen ablation was 12%,
      as compared with 39% for 117 patients treated with 3D-CRT alone who underwent a
      biopsy (P < .001). CONCLUSION: For patients treated with NAAD and high-dose 3D
      CRT, pretreatment PSA, preradiotherapy PSA nadir response, and clinical stage are
      important predictors of biochemical outcome. Patients with NAAD-induced PSA nadir
      levels greater than 0.5 ng/mL before radiotherapy are more likely to develop
      biochemical failure and may benefit from more aggressive therapies.

PMID- 9779717
TI  - Secondary leukemia following high cumulative doses of etoposide in patients
      treated for advanced germ cell tumors.
AB  - PURPOSE: High cumulative epipodophyllotoxin dosages are reported to be associated
      with an elevated risk for secondary acute myeloid leukemia (s-AML). This study
      examined the risk of s-AML following cumulative etoposide doses greater than 2
      g/m2 in patients with metastatic germ cell tumors (GCT). PATIENTS AND METHODS:
      The incidence of s-AML was retrospectively assessed in patients treated within
      clinical trials between January 1986 and February 1996 at four university
      centers. All patients received high-dose chemotherapy (HDCT) plus autologous stem
      cell support for metastatic GCT, including high cumulative etoposide doses (> 2
      g/m2). Minimum patient follow-up was 12 months. Standardized morbidity ratio
      (SMR) was calculated to estimate the risk associated with high cumulative
      etoposide doses, as compared with the general population. RESULTS: A total of 302
      patients with a median age of 29 years (range, 15 to 55) received a median
      cumulative etoposide dose of 5 g/m2 (range, 2.4 to 14 g/m2). Four cases of s-AML
      were observed, which resulted in a cumulative incidence of 1.3% (95% confidence
      interval [CI], 0.38% to 3.59%) at 52 months of median follow-up (range, 12 to
      198). Two cases of secondary myelodysplasia (s-MDS) developed in patients with
      primary mediastinal GCT. Based on the observed four cases of AML, which are most
      likely etoposide-related, the risk for developing s-AML (SMR, 160 [95% CI, 43.7
      to 411.2]) is significantly increased in comparison to the age-matched general
      population. CONCLUSION: Due to the low incidence of AML in the general
      population, the significantly elevated risk for developing s-AML affects only
      1.3% of all patients who receive etoposide doses greater than 2 g/m2. HDCT,
      including etoposide doses greater than 2 g/m2, is associated with an acceptably
      low incidence of s-AML in patients with advanced GCT.

PMID- 9779718
TI  - Docetaxel and cisplatin in metastatic urothelial cancer: a phase II study.
AB  - PURPOSE: Docetaxel and cisplatin has documented single-agent activity and
      different toxicity profiles in patients with metastatic urothelial cancer. We
      performed a phase II study in which docetaxel was combined with cisplatin to
      evaluate response rate, toxicity, and survival. PATIENTS AND METHODS: Eligibility
      criteria included performance status (World Health Organization [WHO]) less than
      3; normal bone marrow, liver, and renal function; and no concurrent malignancy or
      symptomatic peripheral neuropathy. Docetaxel (Taxotere; Rhone-Poulenc Rorer,
      Paris, France) 75 mg/m2 was combined with cisplatin 75 mg/m2 every third week.
      Patients received premedication with prednisolone and clemastine. RESULTS: A
      total of 25 patients were assessable for response and toxicity. Median age was 64
      years; five patients had locoregional disease only and 20 had metastatic disease.
      Response was achieved in 15 patients (60%; 95% confidence interval [CI], 39% to
      79%), including seven patients (26%) who achieved a complete response. Overall
      median survival time was 13.6 months (range, 1.5 to 26.4+). The most frequent
      toxicity was nausea and vomiting (80% of patients). Neutropenia grade 3 or 4 was
      observed in 56% of patients, but only one had febrile neutropenia. Mucositis and
      diarrhea were encountered in 13% of cycles, mostly grade 1 or 2. Peripheral
      neuropathy and skin changes grade 1 and 2 were observed in 76% and 36%,
      respectively. Fluid retention and hypersensitivity reactions were infrequent and
      mild. CONCLUSION: The combination of docetaxel and cisplatin is effective and
      feasible in patients with metastatic urothelial cancer with a manageable safety
      profile.

PMID- 9779719
TI  - Apples and oranges: building a consensus for standardized eligibility criteria
      and end points in prostate cancer clinical trials.
AB  - PURPOSE: To survey eligibility and response criteria for clinical trials in
      hormone-refractory prostate cancer (HRPC). METHODS: Thirty-five established
      investigators of HRPC completed a 125-question survey. RESULTS: There was a
      general consensus that criteria for clinical trial entry would include
      progression based on an increasing prostate-specific antigen (PSA) level (94% of
      investigators), an increase in measurable disease (91%), and/or appearance of new
      bone lesions on bone scan (83%). Most believed that castrate levels of
      testosterone (77%) and progression after antiandrogen withdrawal (97%) should be
      documented before study enrollment. Continuation of testicular androgen
      suppression would be required by 82%. Seventy-seven percent favored separate
      reports on response rates in bone, measurable disease, symptoms, and biochemical
      markers (primarily PSA levels), rather than a composite response. Ninety-four
      percent of the investigators accepted changes in PSA level as a surrogate end
      point of response. However, interpretation by these investigators of a PSA data
      set similar to what might be observed in a clinical trial showed marked
      discordance. Survival is the end point of most importance to 94% of these
      investigators. Response based on changes in measurable disease, time to
      progression, response duration, PSA level decrease, or quality-of-life
      improvement were of similar weighted value as a clinical trial end point and were
      rated as less important to these investigators than survival (P < 10(-8)).
      CONCLUSION: This survey indicates some consensus on eligibility and concomitant
      treatments for clinical studies in HRPC. The use of multiparameter assessment of
      response and PSA level as a surrogate end point have been widely adopted.

PMID- 9779720
TI  - Diagnostic and prognostic value of peritoneal immunocytology in gastric cancer.
AB  - PURPOSE: Among the clinical factors with a pivotal role in the prediction of
      outcome for patients with gastric cancer, intraperitoneal (i.p.) microscopic
      dissemination may represent an important cause of recurrences, even in the early
      stages of the disease. In this context, the cytologic examination of
      intraoperative peritoneal washings may be essential to identify metastatic free
      cells, although a number of false-negative cases may be encountered. PATIENTS AND
      METHODS: To determine whether immunocytochemical (ICC) methods that used a panel
      of three monoclonal antibodies (MoAbs), B72.3, AR3, and BD5, directed to gastric
      cancer-associated antigens can improve peritoneal cytology by providing more
      accurate prognostic indications, we immunocytochemically and morphologically
      evaluated 144 peritoneal washings sampled from patients surgically treated for
      gastric cancer. RESULTS: The ICC analysis allowed the identification of
      metastatic free peritoneal cells in 35% of the patients, with a 14% improvement
      over routine cytopathology (P < .0001). Furthermore, a 54-month survival analysis
      by Kaplan-Meier curves showed a statistically significant decrease in overall
      survival (OS) in patients with stages I through III disease with peritoneal
      microscopic disease detected morphologically and/or by ICC at the time of the
      primary surgery. CONCLUSION: Our data indicate that the use of a combination of
      selected MoAbs may allow the identification of cytologically false-negative cases
      that provide valuable prognostic information. This may be useful to stratify
      patients on more adequate therapeutic trials.

PMID- 9779721
TI  - Quality-of-life benefit in chemotherapy patients treated with epoetin alfa is
      independent of disease response or tumor type: results from a prospective
      community oncology study. Procrit Study Group.
AB  - PURPOSE: To evaluate prospectively the effectiveness of epoetin alfa as an
      adjunct to chemotherapy in patients with cancer based on changes in quality-of
      life parameters and hemoglobin levels, and to correlate these changes with
      antitumor response. PATIENTS AND METHODS: Two thousand three hundred seventy
      patients with nonmyeloid malignancies who received chemotherapy were enrolled
      onto this study from 621 US community-based practices. Patients received epoetin
      alfa 10,000 U three times weekly, which could be increased to 20,000 U three
      times weekly depending on the hemoglobin response at 4 weeks. Treatment continued
      for a maximum of 16 weeks in patients who showed evidence of hematologic
      response. RESULTS: Two thousand two hundred eighty-nine patients (97%) were
      eligible for efficacy analyses. Epoetin alfa therapy was associated with improved
      quality-of-life parameters; these improvements correlated significantly with
      hemoglobin levels and were independent of tumor response. Provider-reported
      Karnofsky performance scores did not correlate with the improved quality-of-life
      changes. Epoetin alfa therapy was also associated with a significant increase in
      hemoglobin levels and decrease in transfusion use. Tumor type, chemotherapy
      agent/regimen, prior chemotherapy, baseline hemoglobin level, and baseline
      erythropoietin level were not predictive of a positive response to treatment.
      Epoetin alfa was well tolerated. CONCLUSION: Epoetin alfa appears to have a
      beneficial impact on patient-reported functional capacity and quality of life in
      patients with cancer who received chemotherapy independent of tumor response.
      Concordantly, epoetin alfa appeared to increase hemoglobin levels and decrease
      transfusion use. Patients responded across all tumor types. The results suggest
      that epoetin alfa effectively improves functional outcomes in patients with
      cancer who receive chemotherapy.

PMID- 9779722
TI  - Capillary protein leak syndrome appears to explain fluid retention in cancer
      patients who receive docetaxel treatment.
AB  - PURPOSE: The aim of our study was to elucidate whether the fluid retention
      syndrome induced by docetaxel is caused by capillary protein leakage or by other
      mechanisms. PATIENTS AND METHODS: Twenty-four patients with advanced or
      metastatic non-small-cell lung cancer (NSCLC; 23 patients) or metastatic head and
      neck cancer (one patient) were included on this prospective, nonrandomized trial.
      Docetaxel 100 mg/m2 was administered every 3 weeks with 5 days of dexamethasone
      prophylaxis to avoid hypersensitivity reactions and edema formation.
      Transcapillary forces, ie, colloid osmotic pressure of plasma (COPpl) and
      interstitial fluid (COPint) and interstitial hydrostatic pressure (Pint), were
      measured before the start of treatment and after total docetaxel doses of 200 and
      500 mg/m2 by means of the well-documented wick and wick-in-needle methods. Body
      weight, degree of edema, blood pressure, and heart rate and hemoglobin,
      hematocrit, albumin, and total protein values were registered in parallel.
      RESULTS: After a total docetaxel dose of 200 mg/m2, COPpl, COPint, and
      hemoglobin, hematocrit, albumin, and total protein values had decreased
      significantly; Pint and body weight were unchanged; and only mild edema was
      observed. These findings suggest a plasma volume increase followed by enhanced
      fluid filtration to the interstitium. After a cumulative docetaxel dose of 500
      mg/m2, the COPpl continued to decrease significantly, but COPint remained
      unchanged despite a significant increase in mean body weight and edema formation.
      These observations support the theory of a capillary protein leakage. CONCLUSION:
      Docetaxel appears to induce an initial enhancement of fluid filtration followed
      by a capillary protein leakage that leads to edema formation.

PMID- 9779723
TI  - Scientific misconduct in cancer clinical trials.

PMID- 9779725
TI  - Uracil-ftorafur: an oral fluoropyrimidine active in colorectal cancer.
AB  - PURPOSE AND DESIGN: This review describes the early clinical development of
      uracil-ftorafur (UFT), an oral fluoropyrimidine, designed in 1978 by adding
      uracil to ftorafur. The review focuses on the treatment of colorectal cancer and
      summarizes the Japanese experience and the phase I and II trials performed in the
      United States and Europe. RESULTS: Clinical trials of UFT published in the
      Western world have included 581 patients with colorectal cancer. UFT has been
      administered in these trials as a single agent or biomodulated by leucovorin
      (LV). UFT was administered daily in split doses for periods that ranged from 14
      to 28 days. The activity of oral UFT in large-bowel cancer when administered with
      oral LV (approximately 50 mg/dose) has resulted in objective response rates of
      approximately 40%. Response rates of approximately 25% (range, 17% to 39%) were
      reported when UFT was administered as a single agent or with lower doses of LV.
      The highest dose-intensities of UFT are achieved with 28-day schedules of
      administration. The maximum-tolerated dose (MTD) of UFT with this schedule, when
      administered concomitantly with oral LV 150 mg daily, is 300 mg/m2 daily. The
      dose-limiting toxicity (DLT) of UFT has generally been diarrhea. Other commonly
      described toxicities include nausea and vomiting, fatigue, and stomatitis.
      Myelosuppression occurs infrequently. Typically, hand-foot syndrome and
      neurologic toxicity are lacking. CONCLUSION: UFT is a fluoropyrimidine active in
      colorectal cancer. The oral route of administration and improved safety profile
      represent important advantages over both conventional and infusional fluorouracil
      (5-FU) regimens.

PMID- 9779724
TI  - Cytotoxic and hormonal treatment for metastatic breast cancer: a systematic
      review of published randomized trials involving 31,510 women.
AB  - PURPOSE: A systematic review of randomized clinical trials (RCTs) was undertaken
      to assess the effectiveness of medical treatment for metastatic breast cancer.
      METHODS: RCTs published between 1975 and 1997 have been classified according to
      12 therapeutic comparisons: (1) polychemotherapy (PCHT) agents versus single
      agent; (2) PCHT regimens with anthracycline versus PCHT without anthracycline;
      (3) other PCHT versus cyclophosphamide, methotrexate, and fluorouracil (CMF); (4)
      chemotherapy (CHT) with epirubicin versus CHT with doxorubicin; (5) CHT versus
      same CHT delivered with less intensive schedules; (6) other endocrine therapy
      (OET) versus tamoxifen; (7) OET plus tamoxifen versus tamoxifen alone; (8) OET
      versus medroxyprogesterone; (9) OET versus aromatase inhibitors; (10) OET versus
      megestrol; (11) endocrine therapy (ET) versus same ET at lower doses; and (12)
      CHT plus ET versus CHT. Tumor response rates, mortality hazards ratio (HR) and
      frequency of severe side effects were the outcome measures. RESULTS: A total of
      189 eligible trials (31,510 patients) were identified. All provided response
      rates and 133 (70%) data or survival curves needed for calculation of the HR. In
      eight of 12 comparisons, statistically significant differences for response
      emerged (1, 2, 3, 5, 7, 8, 11, 12); all but no. 8 favored the first term of the
      comparison. Overall survival analysis showed better results of (a) PCHT versus
      single-agent CHT (HR=0.82; 95% confidence interval [CI], 0.75 to 0.90); (b) CHT
      with doxorubicin versus CHT with epirubicin (HR=1.13; 95% CI, 1.00 to 1.27); (c)
      CHT versus the same CHT delivered with less intensive schedules (HR=0.90; 95% CI,
      0.83 to 0.97); (d) ET versus the same ET at lower doses (HR=0.86; 95% CI, 0.77 to
      0.97). Quality of life was measured in only 2,995 of 31,510 patients (9.5%).
      CONCLUSION: Despite some evidence of effectiveness of specific regimens, the
      relevance of these findings is limited by the modest survival benefit and the
      lack of evaluation of the quality-of-life impact of these treatments.

PMID- 9779726
TI  - Pneumocystis carinii pneumonia with peripheral nodular infiltrates in a patient
      with T-acute lymphoblastic leukemia.

PMID- 9779727
TI  - An open letter to the American Society of Clinical Oncology.

PMID- 9779728
TI  - Posttransplant Kaposi's sarcoma treated with paclitaxel.

PMID- 9779729
TI  - Radiotherapy with/without cisplatin following chemotherapy in limited small-cell
      lung cancer.

PMID- 9779731
TI  - Conceptual and linguistic biases in children's word learning.
AB  - Four studies examined the influence of essentialist information and perceptual
      similarity on preschoolers' interpretations of labels. In Study 1, 3-, 4-, and 5
      year-olds were less likely to interpret 2 labels for animals as referring to
      mutually exclusive categories: when the animals were said to share internal,
      rather than superficial, properties and when the animals were perceptually
      similar rather than dissimilar. In Study 2, neither internal nor functional
      property information influenced 4-year-olds' interpretations of labels for
      artifacts. Studies 3 and 4 provide baseline data, demonstrating that the domain
      differences were not due to prior differences in children's lexical knowledge in
      the 2 domains. These results suggest that children have essentialist beliefs
      about animals, but not about artifacts, and that these beliefs interact with
      children's assumptions about word meaning in determining their interpretations of
      labels.

PMID- 9779730
TI  - Intentional communication by chimpanzees: a cross-sectional study of the use of
      referential gestures.
AB  - This study describes the use of referential gestures with concomitant gaze
      orienting behavior to both distal food objects and communicative interactants by
      115 chimpanzees, ranging from 3 to 56 years of age. Gaze alternation between a
      banana and an experimenter was significantly associated with vocal and gestural
      communication. Pointing was the most common gesture elicited; 47 subjects pointed
      with the whole hand, whereas 6 subjects pointed with index fingers. Thus,
      communicative pointing is commonly used by laboratory chimpanzees, without
      explicit training to point, language training, or home rearing. Juveniles
      exhibited striking decrements in their propensity to communicate with adult male
      experimenters compared with older chimpanzees. Significantly fewer mother-reared
      chimpanzees exhibited gaze alternation compared with nursery-reared chimpanzees.

PMID- 9779732
TI  - Audition and visual attention: the developmental trajectory in deaf and hearing
      populations.
AB  - This study examined the development of visual attention in 5- to 13-year-olds who
      differed in their access to sound. Hearing children, deaf children with cochlear
      implants, and deaf children without implants participated in a task in which they
      were to respond to some visual signals and not others. The results of Experiment
      I indicated that the timing of developmental changes in visual selective
      attention was similar for all 3 groups, occurring around 8 years. The magnitude
      of age-related change differed among groups; hearing children and older deaf
      children using a cochlear implant reached higher levels of performance with age
      than did deaf children without enhanced access to sound. The results of
      Experiment 2 suggest that the developmental differences between deaf children
      with and without cochlear implants begin prior to 8 years and may be related to
      their use of environmental sounds to organize visual attention.

PMID- 9779733
TI  - Independence of age-related influences on cognitive abilities across the life
      span.
AB  - Age-related increases in childhood and age-related decreases in adulthood have
      been reported for a wide variety of cognitive variables, but relatively little
      research has addressed the question of the independence of these influences. In
      this project, cross-sectional life span data (age 5 to 94 years) from the
      nationally representative sample used to establish the norms for the Woodcock
      Johnson Psycho-Educational Battery (R. W. Woodcock & M. B. Johnson, 1989, 1990)
      were subjected to several types of analyses. The results indicated that the
      majority of age-related differences appear to be shared across different
      cognitive variables and are well predicted by individual differences in higher
      order factors. These findings suggest that the role of task-specific
      interpretations of developmental differences in cognition needs to be reevaluated
      to take into consideration the lack of independence of age-related influences on
      a variety of cognitive variables.

PMID- 9779735
TI  - The role of conceptual understanding in children's addition problem solving.
AB  - The study examined the relationship between children's conceptual understanding
      and addition problem-solving procedures. Forty-eight 6- to 8-year-olds solved
      addition problems and, in a 2nd task, were prompted to judge whether a puppet
      could use the arithmetic properties of one problem to solve the next problem.
      Relational properties between consecutive problems were manipulated to reflect
      aspects of additive composition, commutativity, and associativity principles.
      Conceptual understanding was assessed by the ability to spontaneously use such
      relational properties in problem solving (Task 1) and to recognize and explain
      them when prompted (Task 2). Results revealed that conceptual understanding was
      related to using order-indifferent, decomposition, and retrieval strategies and
      speed and accuracy in solving unrelated problems. The importance of conceptual
      understanding for addition development is discussed.

PMID- 9779734
TI  - Representations as mediators of adolescent deductive reasoning.
AB  - In Experiment 1, preadolescents, middle adolescents, and late adolescents were
      presented 3 deductive reasoning tasks. With some important exceptions,
      conditional reasoning improved with age on problems containing permission
      conditional relations, and reasoning fallacies increased with age on problems
      containing causal conditional relations. The results of Experiments 2a and 2b
      indicated that problem type (i.e., permission or causal) does not mediate the
      activation of conditional reasoning skills. Rather, valid conditional inferences
      are more common on problems for which plausible alternative antecedents can be
      generated than on problems for which alternative antecedent generation is
      difficult. Conditional rules for which alternative antecedent generation is
      difficult may be misrepresented as biconditionals, resulting in biconditional
      rather than conditional reasoning.

PMID- 9779736
TI  - Level of voice among female and male high school students: relational context,
      support, and gender orientation.
AB  - Adolescence brings with it displays of false self-behavior, including the
      suppression of opinions. C. Gilligan (1993) argued that lack of "voice" is
      problematic for girls when they enter adolescence. In the present study, the
      authors examined level of self-reported voice with parents, teachers, male
      classmates, female classmates, and close friends among both female and male high
      school students. Findings revealed no gender differences nor evidence that voice
      declines in female adolescents. For both genders, perceived support for voice was
      predictive of level of voice. Moreover, feminine girls reported lower levels of
      voice than did androgynous girls in public (but not private) relational contexts.
      Lower levels of voice were associated with more negative evaluations of self
      worth. Discussion focused on the need to understand the causes of individual
      differences in voice within each gender, cautioning against generalizations about
      either gender as a group.

PMID- 9779737
TI  - Children's subjective identification with the group and in-group favoritism.
AB  - Recent developments in social psychology have explained children's preference for
      members of the in-group in terms of processes of self-categorization and
      identification with the in-group. In contrast, this study, addressing nationality
      self-conceptions, examines the possibility that even before subjective
      identification with the group has occurred, as de facto group members, children
      will have been exposed to a great deal of positive information about their own
      national group, which is likely to encourage group-serving judgments. Children
      who had failed to identify themselves as members of their national group were
      required in this study to make evaluative judgments about 5 national groups,
      including their own. Significant preference for the in-group emerged on 2 of 3
      measures. It is concluded that subjective identification with the in-group is not
      a necessary precondition for in-group favoritism.

PMID- 9779738
TI  - Contemporaneous and longitudinal prediction of children's sympathy from
      dispositional regulation and emotionality.
AB  - The relation of 8- to 10-year-olds' teacher-reported dispositional sympathy to
      regulation and emotionality was examined with a longitudinal sample. In general,
      sympathy was correlated with adults' reports of regulation and low negative
      emotionality contemporaneously and, to some degree, 2 and 4 years prior. General
      emotional intensity interacted with some aspects of regulation in predicting
      sympathy; for example, attention focusing predicted sympathy but only for
      children low in general emotional intensity. In general, the pattern of
      correlations changed little from age 6-8 to age 8-10 years, although parent
      reported negative emotionality was more highly negatively related to sympathy at
      the older age. Dispositional sympathy was associated with verbal or physiological
      markers of sympathy in a laboratory setting.

PMID- 9779739
TI  - Maternal attachment representations, maternal sensitivity, and the infant-mother
      attachment relationship.
AB  - The role of maternal sensitivity as a mediator accounting for the robust
      association between maternal attachment representations and the quality of the
      infant-mother attachment relationship was examined. Sixty mother-infant dyads
      were observed at home and in the Strange Situation at 13 months, and mothers
      participated in the Adult Attachment Interview (AAI) within the next 6 months. A
      strong association was found between AAI and Strange Situation classifications,
      and autonomous mothers were more sensitive at home than were nonautonomous
      mothers. Mothers in secure relationships were more sensitive at home than mothers
      in nonsecure relationships. Likewise, infants in secure relationships were more
      secure as assessed by the Waters' Attachment Q sort than infants in nonsecure
      relationships. A test of the mediational model revealed that maternal sensitivity
      accounted for 17% of the relation between AAI and Strange Situation
      classifications.

PMID- 9779740
TI  - Children's interpersonal behaviors and the teacher-child relationship.
AB  - Relations between kindergartners' (N = 199; M age = 5 years 6 months) behavioral
      orientations and features of their 1st-grade teacher-child relationships (i.e.,
      conflict, closeness, dependency) were examined longitudinally. Early behavioral
      orientations predicted teacher-child relationship quality in that (a) unique
      associations emerged between children's early antisocial behavior and features of
      their 1st-grade teacher-child relationships (i.e., negative relation with
      closeness, positive relation with conflict and dependency) and between asocial
      behavior and teacher-child dependency, and (b) prosocial behavior was correlated
      with but not uniquely related to any feature of children's 1st-grade teacher
      child relationships. In addition, specific features of the teacher-child
      relationship (e.g., conflict) predicted changes in children's behavioral
      adjustment (e.g., decreasing prosocial behavior).

PMID- 9779741
TI  - Korean children's concepts of adult and peer authority and moral reasoning.
AB  - This study examined Korean children's judgments about authority commands
      regarding moral events bearing on property rights (dealing with lost property),
      distributive justice (sharing candy), and public welfare (disposing of trash).
      Sixty children from the 1st, 3rd, and 5th grades were presented with story
      variations in which an individual intervened, giving a command to children, or in
      which 2 different persons gave opposing commands. At all ages, children judged
      that a principal, a teacher, a class president, and a child who held no position
      of authority have legitimacy and should be obeyed when giving directives
      considered morally right. Children also accorded greater legitimacy to persons
      giving commands consistent with moral demands (a teacher, a class president, or a
      child with no position of authority) over a principal's command contrary to the
      moral evaluation. Justifications for their choices were based on rights, sharing,
      and welfare. The findings showed that Korean children do not take a unilateral
      orientation to adult authorities or unquestioningly accept authority directives.

PMID- 9779742
TI  - A neuropsychological examination of the underlying deficit in attention deficit
      hyperactivity disorder: frontal lobe versus right parietal lobe theories.
AB  - A neuropsychological approach was used to examine the frontal lobe and right
      parietal lobe theories of attention deficit hyperactivity disorder (ADHD).
      Considerable attempts were made to select as pure a group of ADHD boys as
      possible. The performance of 10-14-year-old ADHD boys (n = 22), both on and off
      stimulant medication, was compared with the performance of non-ADHD control boys
      (n = 22) on tasks purported to assess frontal lobe functioning (Stopping Task,
      Antisaccade Task, Tower of Hanoi) and right parietal lobe functioning (Visual
      Spatial Cuing Task, Turning Task, Spatial Relations). Three important findings
      emerged: (a) unmedicated ADHD boys exhibited performance deficits on tasks in
      both frontal and parietal domains compared with control boys, (b) unmedicated
      ADHD boys appeared to be more severely impaired on the frontal tasks than on the
      parietal tasks, and (c) medicated ADHD boys performed better in both task domains
      compared with unmedicated ADHD boys. Several alternative interpretations of the
      results are discussed.

PMID- 9779743
TI  - Genotype-environment correlations in late childhood and early adolescence:
      antisocial behavioral problems and coercive parenting.
AB  - A key question for understanding the interplay between nature and nurture in
      development is the direction of effects in socialization. A longitudinal adoption
      design provides a unique opportunity to investigate this issue in terms of
      genotype-environment correlations for behavioral problems. As part of the
      Colorado Adoption Project, adopted children were classified as being at genetic
      risk (N = 38) or not at genetic risk (N = 50) for antisocial behavior based on
      their biological mothers' self-report history of antisocial behavior collected
      prior to the birth of the child. From age 7 through age 12, adoptive parents
      reported on the negative control, positive parenting, and inconsistent parenting
      they use in managing their child's behavior. Repeated measures analysis of
      variance indicated that children at genetic risk were consistently more likely to
      receive negative parenting from their adoptive parents than children not at
      genetic risk, indicating an evocative genotype-environment correlation. However,
      the findings also showed that most of the association between negative parenting
      and children's externalizing behavior was not explicable on the basis of an
      evocative gene-environment correlation and that an additional environmentally
      mediated parental effect on children's behavior was plausible.

PMID- 9779745
TI  - Social-cognitive influences on change in aggression over time.
AB  - This study examined whether social cognitions that have been assumed to influence
      aggression actually forecast change in aggressive habits over time. Participants
      were 189 3rd- through 7th-grade boys and girls; data on social cognitions and
      social behaviors were collected in the fall and spring of the school year.
      Aggression-encouraging cognitions assessed in the fall indeed promoted aggression
      over the school year, but such developments hinged critically on child sex and on
      initial (fall) levels of aggression and victimization. Results illustrate the
      principle that cognitions affect behavioral development mainly when the child's
      transactions with the social environment support the use of the cognitions as
      guides for behavior.

PMID- 9779746
TI  - Children's decoding of emotion in expressive body movement: the development of
      cue attunement.
AB  - Little research has focused on children's decoding of emotional meaning in
      expressive body movement: none has considered which movement cues children use to
      detect emotional meaning. The current study investigated the general ability to
      decode happiness, sadness, anger, and fear in dance forms of expressive body
      movement and the specific ability to detect differences in the intensity of anger
      and happiness when the relative amount of movement cue specifying each emotion
      was systematically varied. Four-year-olds (n = 25), 5-year-olds (n = 25), 8-year
      olds (n = 29), and adults (n = 24) completed an emotion contrast task and 2
      emotion intensity tasks. Decoding ability exceeding chance levels was
      demonstrated for sadness by 4-year-olds; for sadness, fear, and happiness by 5
      year-olds: and for all emotions by 8-year-olds and adults. Children as young as 5
      years were shown to rely on emotion-specific movement cues in their decoding of
      anger and happiness intensity. The theoretical significance of these effects
      across development is discussed.

PMID- 9779744
TI  - Interaction of temperamental resistance to control and restrictive parenting in
      the development of externalizing behavior.
AB  - Child temperament and parental control were studied as interacting predictors of
      behavior outcomes in 2 longitudinal samples. In Sample 1, data were ratings of
      resistant temperament and observed restrictive control in infancy-toddlerhood and
      ratings of externalizing behavior at ages 7 to 10 years; in Sample 2, data were
      retrospective ratings of temperament in infancy-toddlerhood, observed restrictive
      control at age 5 years, and ratings of externalizing behavior at ages 7 to 11
      years. Resistance more strongly related to externalizing in low-restriction
      groups than in high-restriction groups. This was true in both samples and for
      both teacher- and mother-rated outcomes. Several Temperament x Environment
      interaction effects have been reported previously, but this is one of very few
      replicated effects.

PMID- 9779747
TI  - Infants' use of attentional cues to identify the referent of another person's
      emotional expression.
AB  - This study explored 14- and 18-month-old infants' ability to identify the target
      of an emotional display. In the visual task, infants were presented with 2 boxes.
      Each box contained an object that could be identified by opening the box lid and
      looking inside. In the tactile task, the objects had to be pulled out of the
      boxes before they could be seen. An experimenter expressed happiness as she
      looked or put her hand inside one box, and disgust as she repeated this action
      with the other box. Infants were then allowed to explore the boxes. Infants
      touched both boxes but preferred to search for the happy object. Thus, regardless
      of age or task, infants identified the target of each emotional display as
      something inside a box and not the box itself. Infants appeared to use the
      experimenter's attentional cues (gaze and action) to interpret her emotional
      signals and behaved as if they understood that she was communicating about the
      objects.

PMID- 9779748
TI  - Understanding mind and emotion: longitudinal associations with mental-state talk
      between young friends.
AB  - Developmental changes in children's understanding of mind and emotion and their
      mental-state talk in conversations with friends were examined in a longitudinal
      study of 50 children (M age at each time point = 3 years 11 months, 4 years 6
      months, 5 years 0 months). Significant and related improvements over time were
      found for both theory-of-mind task performance and affective perspective taking.
      Associated with these cognitive developments were quantitative and qualitative
      changes in children's references to mental states in their conversations with
      friends. Individual differences in theory of mind, emotion understanding, and
      mental-state talk were strikingly stable over the 13-month period. Although there
      were no gender differences in children's task performances, girls showed more
      frequent and more developed mental-state talk than boys.

PMID- 9779749
TI  - Attachment and emotional understanding in preschool children.
AB  - This study was designed to elucidate the association between attachment and
      emotional understanding in preschool children. Forty children between the ages of
      2.5 and 6 years and their mothers participated in the study. Mothers completed
      the Attachment Q-set, and children took part at their preschools in both an
      affective perspective-taking task and a series of interviews concerning naturally
      occurring incidents of emotions. Overall, age and attachment security predicted a
      child's aggregate score on the emotional understanding tasks. However, when the
      score was separated by the valence of the emotion, attachment security and age
      predicted a child's score for only those emotions with a negative valence (e.g.,
      sadness) and not for those emotions with a positive valence (e.g., happiness).
      Thus, a secure attachment relationship seems to be important in fostering a
      child's understanding of emotion, primarily negative emotions.

PMID- 9779750
TI  - Young children's predictions of illness: failure to recognize probabilistic
      causation.
AB  - In this study preschool-age children made predictions for a set of salient
      probabilistic causes. Of interest was whether the children viewed outcomes of
      familiar causes of illness as definite or as probabilistic. In Experiment 1,
      children judged that a common cause would affect all members of a group in the
      same way. In Experiment 2, children believed they could definitely predict
      illness outcomes in a single case. These judgments contrasted with adults'
      variable and uncertain predictions. Children did recognize uncertainty in
      outcomes dependent on voluntary choices. Experiment 3 presented both high- and
      low-potency causes of illness. Children treated all causes of illness as
      nonprobabilistic. These results are discussed in the context of children's
      understanding of causal relations and the sources of variability.

PMID- 9779751
TI  - Memory for medical emergencies experienced by 1- and 2-year-olds.
AB  - Children (13-18 months, 20-25 months, and 26-34 months) who had experienced
      trauma injuries were recruited in a hospital Emergency Room and subsequently
      interviewed about them within days (if verbal) and after 6, 12, and 18 or 24
      months. The youngest children demonstrated little long-term verbal recall,
      whereas a few children in the intermediate group, who could not narrate about
      past events at time of injury, could verbally recall the target events 18 months
      later. Most of the oldest children, who had narrative skills at time of injury,
      demonstrated good verbal recall 2 years later. Illustrative case histories were
      described. Accuracy of recall was low for the youngest children, and although the
      majority of older children's recalled information was accurate, there were still
      many errors.

PMID- 9779752
TI  - Chronic disease and perceived developmental progression in adolescence.
AB  - This study examined whether chronic illness causes delays in adolescents'
      perceived developmental status. Longitudinal data were obtained from 86
      adolescents afflicted with insulin-dependent diabetes mellitus and 103 healthy
      adolescents. The adolescents annually completed a questionnaire pertaining to
      their current developmental status and their desired future developmental status
      in 11 age-specific developmental tasks. Health status and physical maturity were
      also determined. In the first year of the study, the diabetics reported delays
      compared with their healthy peers in some developmental tasks, particularly
      physical maturity and an independent lifestyle. However, the overall
      developmental progression perceived by chronically ill adolescents was
      impressive. The difficulty of balancing normative development with the demands of
      chronic illness is discussed.

PMID- 9779753
TI  - Development of sexual orientation among adolescent and young adult women.
AB  - Although some research suggests that sexual orientation is a stable, early
      appearing trait, interviews with 89 young sexual-minority women revealed that a
      majority of women failed to report at least one of the following: childhood
      indicators of sexual orientation, stability in same-sex attractions, or awareness
      of same-sex attractions prior to the conscious process of sexual questioning.
      Lesbians were not more likely to report these experiences than bisexuals,
      although they reported significantly greater same-sex attractions. Consistent
      with studies on older cohorts, few young women reported exclusive same-sex
      attractions. These findings suggest that recollected consistency among prior and
      current behavior, ideation, and attractions are not systematically associated
      with sexual orientation among contemporary young women.

PMID- 9779754
TI  - Social contagion, adolescent sexual behavior, and pregnancy: a nonlinear dynamic
      EMOSA model.
AB  - Nonlinear dynamic modeling has useful developmental applications. The authors
      introduce this class of models and contrast them with traditional linear models.
      Epidemic models of the onset of social activities (EMOSA models) are a special
      case, motivated by J. L. Rodgers and D. C. Rowe's (1993) social contagion theory,
      which predict the spread of adolescent behaviors like smoking, drinking,
      delinquency, and sexuality. In this article, a biological outcome, pregnancy, is
      added to an earlier EMOSA sexuality model. Parameters quantify likelihood of
      pregnancy for girls of different sexuality statuses. Five different
      sexuality/pregnancy models compete to explain variance in national prevalence
      curves. One finding was that, in the context of the authors' simplified model,
      adolescent girls have an approximately constant probability of pregnancy across
      age and time since virginity.

PMID- 9779755
TI  - Comment on "Social contagion, adolescent sexual behavior, and pregnancy: a
      nonlinear dynamic EMOSA model".
AB  - The epidemic model of the onset of social activities (EMOSA model) for adolescent
      sexuality by J. L. Rodgers, D. C. Rowe, and M. Buster (1998) is examined.
      Strengths of the model include the nonlinear dynamic specification that seems
      reasonably realistic and the potential when used as a theoretical tool to
      generate new hypotheses for further testing at the individual level. Limitations
      include the lack of a well-developed statistical framework, the inability to
      include a variety of predictors to capture both social contagion and individual
      differences in the same model, and the focus on aggregate-level data. The EMOSA
      model for sexuality can be reparameterized to a hazard rate or an event history
      model that eliminates these shortcomings. Growth curve analysis represents
      another analytic alternative for the EMOSA model that also does not have these
      limitations.

PMID- 9779756
TI  - Relations between family predictors and child outcomes: are they weaker for
      children in child care? NICHD Early Child Care Research Network.
AB  - Studies suggesting that family factors predict developmental outcomes more
      strongly for children reared principally by their parents than those with
      extensive early child-care experience stimulated the examination of the
      differential prediction of child outcomes using a subsample of families
      participating in the National Institute of Child Health and Human Development
      (NICHD) Study of Early Child Care. A variety of factors were used to predict
      development of children who averaged 30 hr of nonparental care per week for each
      month of their lives and for those who never experienced more than 10 hr of care
      per week by someone other than their mothers. Multivariate analyses provided no
      evidence that family factors predicted outcomes differentially for these 2
      groups, though exploratory analyses revealed several instances of differential
      prediction.

PMID- 9779757
TI  - Early child-care selection: variation by geographic location, maternal
      characteristics, and family structure.
AB  - More than half of all U.S. infants and toddlers spend at least 20 hr per week in
      the care of a nonparent adult. This article uses survival analysis to identify
      which families are most likely to place their child in care and the ages when
      these choices are made, using data from a national probability sample of 2,614
      households. Median age at first placement is 33 months, but age varies by
      geographic region, mother's employment status during pregnancy, mother's
      education level, and family structure (1 vs. 2 parents, mother's age at 1st
      birth, and number of siblings). Controlling for these effects, differences by
      race and ethnicity are small. Implications for studies of child-care selection
      and evaluations of early childhood programs are discussed.

PMID- 9779758
TI  - The Pediatric Infectious Diseases Society Annual Awards, 1998.

PMID- 9779759
TI  - The "in vivo sensitivity test" for acute otitis media revisited.

PMID- 9779760
TI  - Early eradication of pathogens from middle ear fluid during antibiotic treatment
      of acute otitis media is associated with improved clinical outcome.
AB  - OBJECTIVE: To determine the relation between early bacteriologic eradication and
      clinical outcome of acute otitis media (AOM) in infants and young children
      treated with various antibiotics. STUDY DESIGN: The study group consisted of
      patients ages 3 to 24 months seen at the Pediatric Emergency Room with: (1)
      symptoms and physical findings consistent with AOM of < or = 7 days duration; (2)
      no spontaneous perforation or tympanostomy tubes; (3) positive initial middle ear
      fluid culture; and (4) a follow-up to at least Day 10+/-2 of the study with a
      second culture performed 72 to 96 h after initiation of antibiotic treatment. Any
      patient with a positive middle ear fluid culture 72 to 96 h after initiation of
      antibiotic treatment was considered to have bacteriologic failure. Otologic
      evaluation was done by an otolaryngologist unaware of the culture results and of
      the study drug allocation. A clinical score based on body temperature, report of
      irritability and ear tugging observed by the parents and the appearance and
      redness of the ear drum as observed by the otolaryngologist was also used for
      clinical evaluation. RESULTS: The study group consisted of 123 patients, of whom
      57 (46%) had positive middle ear fluid 72 to 96 h after initiation of antibiotic
      treatment. Clinical failure was observed in 21 of 57 (37%) patients in whom
      bacteriologic eradication did not occur vs. only 2 of 66 (3%) patients with
      bacteriologic eradication after 3 to 4 days of treatment (P < 0.001). Clinical
      score for both moderate and severe disease decreased significantly faster in
      those with bacteriologic eradication than in those in whom middle ear fluid was
      still culture-positive 72 to 96 h after initiation of treatment. CONCLUSION:
      Clinical failures in our population were associated with inability to eradicate
      the causative organisms of AOM from the middle ear fluid within 3 to 4 days after
      initiation of antibiotic therapy. Most patients (including those without
      bacteriologic eradication) improved after 3 to 4 days of treatment, but patients
      with sterile middle ear fluid felt better after 3 to 4 days of treatment than
      patients in whom middle ear fluid was still culture-positive.

PMID- 9779761
TI  - The epidemiology of Haemophilus influenzae type b carriage among infants and
      young children in Santo Domingo, Dominican Republic.
AB  - BACKGROUND: Whether herd immunity will occur with widespread Haemophilus
      influenzae type b (Hib) vaccination in developing countries is dependent on
      whether the vaccines are capable of reducing carriage in these settings. However,
      few population-based studies of Hib carriage in developing countries exist.
      METHODS: To study Hib carriage in the Dominican Republic, we collected
      nasopharyngeal swab specimens from a population-based sample of 983 children 0 to
      47 months old in a periurban area of Santo Domingo. RESULTS: Nasopharyngeal swabs
      of 76 (7.7%) children were positive for Hib. Hib carriage varied by age group
      with a low of 1.5% among 0 to 5 month olds, a peak of 12.5% in 6 to 11 month olds
      and prevalence rates of 6.0, 7.9 and 9.8% among 1-, 2- and 3-year-olds,
      respectively. Hib carriage was 51% lower among currently breast-fed 6 to 11 month
      olds than among those not currently breast-fed (18.2% vs. 9.0%; P=0.08).
      CONCLUSIONS: Infants and young children in Santo Domingo have high rates of Hib
      carriage, characterized by an early peak in carriage that corresponds with the
      peak of risk for Hib meningitis. The ability of Hib vaccines to diminish carriage
      to levels that will effectively reduce transmission and lead to herd immunity in
      this setting needs to be determined.

PMID- 9779763
TI  - Risk factors for the early acquisition of human herpesvirus 6 and human
      herpesvirus 7 infections in children.
AB  - OBJECTIVE: Human herpesviruses 6 and 7 (HHV-6 and HHV-7) are common infections in
      children, but risk factors for their early acquisition have not been described.
      METHODS: Excess sera from children 12 to 31 months of age enrolled in a cross
      sectional, random survey were tested for human herpesviruses 6 and 7 infection,
      as measured by using immuno-blot and immunofluorescence assays. RESULTS: Of 164
      children 131 (80%) had antibody to HHV-6, and 79 (47%) of 167 had antibody to HHV
      7. In logistic regression analysis low income [odds ratio (OR), 2.9; 95%
      confidence intervals (CI), 1.02 to 8.7] and having more than 1 sibling (OR=2.1,
      95% CI=0.9 to 5.1) were risk factors for HHV-6 infection after adjusting for age,
      whereas month of test (OR=2.7, 95% CI=1.3 to 5.9) and Black race (OR=2.0, 95%
      CI=0.9, 4.6) were associated with a higher prevalence of HHV-7 infection. In
      contrast having ever been breast-fed appeared to protect against HHV-7 infection
      (OR=0.5, 95% CI=0.3 to 1.1). CONCLUSIONS: Despite studies linking both HHV-6 and
      HHV-7 with exanthem subitum, risk factors for the early acquisition of HHV-6 and
      HHV-7 are distinct. Subsequent studies investigating the transmission of HHV-6
      should explore family size and other factors associated with poverty, whereas
      breast-feeding should be examined as a protective factor for HHV-7 infection.

PMID- 9779762
TI  - Safety and pharmacokinetics of an intramuscular humanized monoclonal antibody to
      respiratory syncytial virus in premature infants and infants with
      bronchopulmonary dysplasia. The MEDI-493 Study Group.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of lower
      respiratory disease in infants and children. MEDI-493 (palivizumab, Synagis) is a
      humanized monoclonal IgG1 antibody to the fusion protein of RSV, and it is highly
      active in vitro against RSV A and B strains. OBJECTIVE: To describe the safety,
      tolerance, immunogenicity and pharmacokinetics of monthly intramuscular
      injections of MEDI-493 among premature infants and children with bronchopulmonary
      dysplasia and to compare these data with information previously obtained with
      intravenous dosing. DESIGN: A Phase I/II multicenter, open label, escalating dose
      clinical trial. PATIENT POPULATION AND DOSING REGIMEN: Children (n=65) born
      prematurely at < or =35 weeks of gestation who were < or =6 months of age (n=41)
      and children with bronchopulmonary dysplasia who were < or =24 months of age
      (n=24) were enrolled. From 1 to 5 monthly injections were given at doses of 5
      mg/kg (n=11), 10 mg/kg (n=6) and 15 mg/kg (n=48). Serum was collected before
      administration of each dose, 30 days after the last dose, and 2, 7 and 14 days
      after the first and second doses for measurement of MEDI-493 concentrations by
      enzyme-linked immunosorbent assay. RESULTS: The pharmacokinetics of MEDI-493 were
      similar to those of other human IgG1 antibodies. Mean serum MEDI-493
      concentrations were 91.1 microg/ml (range, 52.3 to 174.0) 2 days after the
      initial dose of 15 mg/kg and 49.2 microg/ml (range, 13.5 to 132.0) at 30 days.
      Monthly dosing of 15 mg/kg maintained mean trough concentrations of approximately
      70 microg/ml. These concentrations were similar to previously published trough
      concentrations after i.v. administration. MEDI-493 injections were well
      tolerated. Only three children had adverse events judged to be possibly related
      to MEDI-493. Ten children had transient, low titer anti-MEDI-493 binding titers
      (1:10 to 1:40) which were not associated with a pattern of specific adverse
      events or alterations of MEDI-493 concentrations. Two patients in the 5-mg/kg
      dose group were hospitalized for RSV; no RSV hospitalizations were found in the
      higher dose groups. CONCLUSIONS: MEDI-493 was safe and well-tolerated. Monthly
      intramuscular doses of 15 mg/kg maintained mean trough serum concentrations that
      were above 40 microg/ml (the value associated with 99% reduction of pulmonary RSV
      in the cotton rat model). These concentrations were similar to those previously
      reported with i.v. administration of MEDI-493.

PMID- 9779764
TI  - Persisting Helicobacter antibodies in Finnish children and adolescents between
      two and twenty years of age.
AB  - BACKGROUND: Helicobacter pylori is an important gastric pathogen usually acquired
      in childhood. The presumed lifelong progression of H. pylori infection has
      recently been called into question in some longitudinal studies on children. In
      this follow-up study the prevalence and persistence of H. pylori antibodies in
      Finnish children and adolescents from three communities was determined. METHODS:
      We measured H. pylori antibodies in follow-up serum samples of 337 Finnish
      children who participated in a measles-mumps-rubella vaccine study started in
      1982. All available samples collected in 1983, 1987 and 1995 were studied first;
      additional serum samples collected yearly were studied from children who became
      seropositive during the follow-up period. RESULTS: The overall prevalence of H.
      pylori antibodies was 5.6%. About two-thirds of the Helicobacter infections were
      acquired before the age of 7 years; of the remaining one-third the time of
      seroconversion varied between 7 and 19 years. No seroreverters were found. There
      were no statistically significant differences in the seroprevalence of H. pylori
      antibodies in the three communities studied. CONCLUSIONS: The prevalence of H.
      pylori antibodies in Finnish children studied was low. Although the majority of
      new infections were found in children younger than 7 years of age, new
      Helicobacter infections were acquired throughout childhood and adolescence. Once
      acquired H. pylori infection, as verified by Helicobacter antibodies, persisted.

PMID- 9779765
TI  - Cefpodoxime pharmacokinetics in children: effect of food.
AB  - BACKGROUND: Cefpodoxime, an oral third generation cephalosporin antibiotic, is
      used for the treatment of acute upper respiratory tract infection caused by
      susceptible bacteria in children 5 months to 12 years of age. We report the
      results of a randomized two-way crossover study designed to characterize the
      disposition of a single dose (10 mg/kg) of cefpodoxime proxetil oral suspension
      in children, under fed and fasted conditions. METHODS: Seventeen children (8.4
      months to 12.2 years old, seven female) participated in this study. Each subject
      received a single 10-mg/kg dose of cefpodoxime proxetil oral suspension, after a
      predose fast and again coadministered with food. Repeated blood samples (n=10)
      were obtained during 12 h postdose and cefpodoxime was quantified from plasma by
      high performance liquid chromatography. Plasma concentration vs. time data were
      curve fit for each subject with a nonlinear weighted least squares algorithm, and
      pharmacokinetic parameters were determined from the polyexponential estimates.
      RESULTS: Cefpodoxime disposition was best characterized using a one-compartment
      open model with first order absorption. The area under the plasma concentration
      vs. time curve, Cmax and Ke were not significantly different between fed and
      fasted conditions. However, Tmax was significantly prolonged (fed=2.79+/-1.10 h
      vs. fasted=1.93+/-0.54 h) and Ka was significantly smaller (fed=0.42+/-0.14 h(-1)
      vs. fasted=0.81+/-0.72 h(-1)) in the fed state. CONCLUSIONS: Administration of
      cefpodoxime in the presence of food affected the rate but not the extent of
      absorption. Cefpodoxime proxetil oral suspension can be administered without
      regard to meals in children 6 months to 12 years of age.

PMID- 9779766
TI  - Comparative reactogenicity and immunogenicity of booster doses of diphtheria
      tetanus-acellular pertussis-inactivated poliovirus vaccine and diphtheria-tetanus
      inactivated poliovirus vaccine in preadolescents.
AB  - BACKGROUND: The changing epidemiology of pertussis in France has emphasized the
      need for booster vaccinations in adolescents. Although not previously recommended
      because of the high reactogenicity of whole cell pertussis in children older than
      2 years old, the development of less reactogenic acellular pertussis vaccines
      means that this recommendation may be reconsidered. OBJECTIVES: Assessment of the
      reactogenicity and immunogenicity of a diphtheria-tetanus-acellular pertussis
      inactivated poliovirus (DTPa-IPV=Group 1) vaccine administered as the fifth dose
      in preadolescents in comparison with a commercial diphtheria-tetanus-inactivated
      poliovirus (DT-IPV) (Group 2) vaccine currently recommended for this age group.
      MATERIALS AND METHODS: An open, randomized study involving 115 healthy subjects
      ages 10 to 13 years previously vaccinated with 4 doses of diphtheria-tetanus
      whole cell pertussis-IPV vaccines. Reactogenicity was assessed for 4 days
      postvaccination using diary cards. Immunogenicity based on antibody assays in
      sera taken before and 1 month postvaccination was evaluated for all vaccine
      antigen components. RESULTS: Both vaccines showed good tolerability, local and
      general reactogenicity being similar. For local reactions Group 1=88.1% and Group
      2=86.8%, and for general reactions Group 1=40.7% and Group 2=47.2%. Headache was
      the most frequent general symptom with 27.1% for DTPa-IPV and 39.6% for DT-IPV.
      The incidence of fever was 5.1% with DTPa-IPV and 9.4% for DT-IPV. Good immune
      responses were obtained against all vaccine components. CONCLUSIONS: The
      inclusion of acellular pertussis did not significantly increase the
      reactogenicity of DTPa-IPV in comparison with the currently recommended DT-IPV
      vaccine when given as a fifth dose in preadolescents. To prevent recent
      resurgence of pertussis in France, this vaccine should be preferred as the
      booster dose of DTPa-IPV at 11 to 13 years of age as recently approved by the
      National Council of Hygiene of France.

PMID- 9779767
TI  - Recurrent group A streptococcal tonsillopharyngitis.
AB  - OBJECTIVE: To examine the epidemiology and treatment of group A beta-hemolytic
      streptococcal (GABHS) recurrent tonsillopharyngitis in private pediatric
      practice. METHODS: This was a retrospective chart review study covering the time
      span 1975 to 1996 involving 2140 GABHS episodes. Diagnosis was based on acute
      clinical symptoms and laboratory confirmation (throat culture or positive rapid
      antigen detection test) of GABHS. RESULTS: Eighty percent (n=1721) of the
      episodes evaluated were treated with penicillin or amoxicillin; 352 (20.5%) of
      these were followed by a recurrence within 30 days and 519 (30.2%) within 60
      days. GABHS recurrences within 30 days after penicillin/amoxicillin treatment
      rose from 9% in 1975 to 1979 to 25.9% in 1980 to 1984, 24.2% in 1985 to 1989,
      22.4% in 1990 to 1994 and 25.9% in 1995 to 1996 (P < 0.02); 53.4% of the
      recurrences were associated with symptoms and signs of GABHS tonsillopharyngitis,
      9.9% were asymptomatic and 36.7% could not be classified. Recurrences within 60
      days after penicillin/ amoxicillin treatment rose from 10.7% in 1975 to 1979 to
      38.7% in 1980 to 1984, 39.0% in 1985 to 1989, 31.7% in 1990 to 1994 and 37.5% in
      1995 to 1996 (P < 0.001). Recurrent GABHS infections occurred more frequently in
      younger children (1 to 8 years of age, 21.3% recurrence rate) than in adolescents
      (13 to 19 years, 5% recurrence rate; P=0.002). Recurrences within 30 days
      occurred more often after therapy with penicillin (21.8% of 1581 episodes) than
      with cephalosporins (8.6% of 254 episodes) (P < 0.0001) or with macrolides (14.0%
      of 143 episodes, P=0.04). Recurrence rates were unaffected by patient gender or
      season of the year. CONCLUSIONS: Recurrent GABHS infections occur more frequently
      in the 1990s than the 1970s, occur more frequently in children younger than 8
      years of age than in adolescents and occur more frequently after penicillin
      treatment than with alternative antibiotic therapy.

PMID- 9779768
TI  - Azithromycin compared with rifampin for eradication of nasopharyngeal
      colonization by Neisseria meningitidis.
AB  - OBJECTIVES: To evaluate the efficacy and safety of azithromycin compared with
      rifampin for eradication of nasopharyngeal carriage of Neisseria meningitidis
      METHODS: Pharyngeal swabs were obtained from 500 students attending nursing
      school in Cairo, Egypt, to determine the colonization rate with N. meningitidis.
      Colonized individuals were randomized to receive azithromycin (500 mg once) or
      rifampin (600 mg twice daily for four doses). Subjects were then recultured 1 and
      2 weeks posttreatment to determine the effectiveness of the antibiotic therapy
      for eradication of meningococcal nasopharyngeal colonization. RESULTS:
      Individuals treated with azithromycin had a 93% eradication rate at 1 and 2 weeks
      posttreatment comparable with 95 and 91%, respectively, for rifampin. No
      significant side effects were reported by any subjects treated with either
      antibiotic. CONCLUSION: Azithromycin is effective in the eradication of N.
      meningitidis from the nasopharynx of asymptomatic colonized individuals and
      deserves further evaluation for use as prophylaxis against N. meningitidis.

PMID- 9779770
TI  - Pneumococcal vaccines for children: an update.

PMID- 9779769
TI  - Association of fungal colonization and invasive disease in very low birth weight
      infants.
AB  - BACKGROUND: Fungi are common pathogens of nosocomial infections in the very low
      birth weight (VLBW) infants. The purpose of this study was to investigate the
      fungal colonization rate in VLBW infants and the association between fungal
      colonization and systemic fungal diseases. MATERIALS: Between January 1, 1996,
      and December 31, 1996, 116 infants with birth weight < 1500 g admitted to the
      neonatal intensive care unit of Chang Gung Children's Hospital in the first day
      of life were included in this prospective study. METHODS: Cultures from
      oropharynx, rectum, skin (groin and axilla), bag urine and endotracheal aspirates
      were obtained in the first 24 h after birth and weekly thereafter throughout
      their neonatal intensive care unit stay. Medical records were reviewed weekly.
      RESULTS: Fungal colonization was detected in 25 infants, among whom 17 infants
      developed colonization by 2 weeks of life. Candida albicans (61%) and Candida
      parapsilosis (29%) were the 2 most common organisms. The rectum (76%) was the
      most frequent site of colonization. Factors significantly associated with
      colonization were prolonged administration of antibiotic therapy, parenteral
      nutrition and intralipid emulsion. Three of 116 infants developed fungemia. The
      association between colonization and subsequent fungemia was demonstrated in 1
      infant, representing 4% of colonized infants. CONCLUSION: Fungal colonization was
      detected in one-fifth of VLBW infants and represents a risk factor for fungemia.
      Because disease occurred in the absence of apparent colonization, factors other
      than colonization may contribute to invasive candidiasis.

PMID- 9779771
TI  - Prevention of bacterial endocarditis: highlights of the latest recommendations by
      the American Heart Association.

PMID- 9779772
TI  - Control of methicillin-resistant Staphylococcus aureus and vancomycin-resistant
      enterococcus in hospitalized children.

PMID- 9779773
TI  - Viral croup: current diagnosis and treatment.

PMID- 9779774
TI  - Survival from pulmonary infection with Cunninghamella bertholletiae: case report
      and review of the literature.

PMID- 9779775
TI  - Needle aspirate culture method in soft tissue infections: injection of saline vs.
      direct aspiration.

PMID- 9779776
TI  - Travel consultation for children in a university-affiliated primary care setting.

PMID- 9779777
TI  - Lack of association of transient synovitis of the hip joint with human parvovirus
      B19 infection in children.

PMID- 9779778
TI  - Subacute orbital abscess in a four-year-old girl with a new kitten.

PMID- 9779779
TI  - Hemolytic-uremic syndrome caused by Escherichia coli O157:H7 after perforated
      appendix.

PMID- 9779780
TI  - Role of CCR5 chemokine receptor gene in vertical human immunodeficiency virus
      type 1 transmission and disease progression.

PMID- 9779781
TI  - Fever, hemoptysis and pneumonia in a twelve-year-old girl.

PMID- 9779782
TI  - Measles vaccine failure and infections.

PMID- 9779783
TI  - Probable actinic Rocky Mountain spotted fever.

PMID- 9779784
TI  - Improving the accuracy of protein pKa calculations: conformational averaging
      versus the average structure.
AB  - Several methods for including the conformational flexibility of proteins in the
      calculation of titration curves are compared. The methods use the linearized
      Poisson-Boltzmann equation to calculate the electrostatic free energies of
      solvation and are applied to bovine pancreatic trypsin inhibitor (BPTI) and hen
      egg-white lysozyme (HEWL). An ensemble of conformations is generated by a
      molecular dynamics simulation of the proteins with explicit solvent. The average
      titration curve of the ensemble is calculated in three different ways: an average
      structure is used for the pKa calculation; the electrostatic interaction free
      energies are averaged and used for the pKa calculation; and the titration curve
      for each structure is calculated and the curves are averaged. The three averaging
      methods give very similar results and improve the pKa values to approximately the
      same degree. This suggests, in contrast to implications from other work, that the
      observed improvement of pKa values in the present studies is due not to averaging
      over an ensemble of structures, but rather to the generation of a single properly
      averaged structure for the pKa calculation.

PMID- 9779785
TI  - Enthalpy and heat capacity changes for the proton dissociation of various buffer
      components in 0.1 M potassium chloride.
AB  - Enthalpy and heat capacity changes for the deprotonation of 18 buffers were
      calorimetrically determined in 0.1 M potassium chloride at temperatures ranging
      from 5 to 45 degrees C. The values of the dissociation constant were also
      determined by means of potentiometric titration. The enthalpy changes for the
      deprotonation of buffers, except for the phosphate and glycerol 2-phosphate
      buffers, were found to be characterized by a linear function of temperature. The
      enthalpy changes for the second dissociation of phosphate and glycerol 2
      phosphate where divalent anion is formed on dissociation were fitted with the
      second order function of temperature rather than the first order. Temperature
      dependence of buffer pH calculated by using the enthalpy and heat capacity
      changes obtained was in good agreement with the temperature variation of the pH
      values actually measured in the temperature range between 0 and 50 degrees C for
      all the buffers studied. On the basis of the results obtained, a numeric table
      showing the temperature dependence of pK values for the 18 buffers is presented.

PMID- 9779786
TI  - Analysis of N-terminal capping using carbonyl-carbon chemical shift measurements.
AB  - The model peptide XAAAAEAAARAAAARamide is used to examine the contributions of an
      N-terminal capping interaction to the conformation and stability of a helical
      ensemble. The reference peptide has an alanine residue at position X while the
      capping peptide has a serine residue at this position. The helical ensemble was
      characterized using circular dichroism measurements and carbonyl-carbon chemical
      shift measurements of selectively enriched residues. The distribution of helicity
      within the ensemble of the reference peptide at pH 11 and 0 degrees C appears
      symmetrical, having a uniform central helix and frayed ends. This distribution is
      truncated at pH 6 by the repulsive electrostatic interaction between the
      positively charged alpha-amino group and the positively charged end of the
      helical macrodipole. The capping peptide forms a side-chain/ main-chain hydrogen
      bond involving the serine residue and amide of alanine 4. The presence of this
      hydrogen bond generates a unique motif in the chemical shift profile of its
      helical ensemble. The conformational stabilization contributed by this hydrogen
      bond, although cooperatively distributed throughout the helical ensemble, is
      preferentially focused within the first helical turn. The stabilization provided
      by this hydrogen bond is able to offset the truncation of the helical ensemble
      generated by the repulsive electrostatic interaction observed at pH 6.

PMID- 9779787
TI  - Use of quantitative structure-property relationships to predict the folding
      ability of model proteins.
AB  - We investigate the folding of a 125-bead heteropolymer model for proteins subject
      to Monte Carlo dynamics on a simple cubic lattice. Detailed study of a few
      sequences revealed a folding mechanism consisting of a rapid collapse followed by
      a slow search for a stable core that served as the transition state for folding
      to a near-native intermediate. Rearrangement from the intermediate to the native
      state slowed folding further because it required breaking native-like local
      structure between surface monomers so that those residues could condense onto the
      core. We demonstrate here the generality of this mechanism by a statistical
      analysis of a 200 sequence database using a method that employs a genetic
      algorithm to pick the sequence attributes that are most important for folding and
      an artificial neural network to derive the corresponding functional dependence of
      folding ability on the chosen sequence attributes [quantitative structure
      property relationships (QSPRs)]. QSPRs that use three sequence attributes yielded
      substantially more accurate predictions than those that use only one. The results
      suggest that efficient search for the core is dependent on both the native
      state's overall stability and its amount of kinetically accessible, cooperative
      structure, whereas rearrangement from the intermediate is facilitated by
      destabilization of contacts between surface monomers. Implications for folding
      and design are discussed.

PMID- 9779788
TI  - Accuracy of side-chain prediction upon near-native protein backbones generated by
      Ab initio folding methods.
AB  - The ab initio folding problem can be divided into two sequential tasks of
      approximately equal computational complexity: the generation of native-like
      backbone folds and the positioning of side chains upon these backbones. The
      prediction of side-chain conformation in this context is challenging, because at
      best only the near-native global fold of the protein is known. To test the effect
      of displacements in the protein backbones on side-chain prediction for folds
      generated ab initio, sets of near-native backbones (< or = 4 A C alpha RMS error)
      for four small proteins were generated by two methods. The steric environment
      surrounding each residue was probed by placing the side chains in the native
      conformation on each of these decoys, followed by torsion-space optimization to
      remove steric clashes on a rigid backbone. We observe that on average 40% of the
      chi1 angles were displaced by 40 degrees or more, effectively setting the limits
      in accuracy for side-chain modeling under these conditions. Three different
      algorithms were subsequently used for prediction of side-chain conformation. The
      average prediction accuracy for the three methods was remarkably similar: 49% to
      51% of the chi1 angles were predicted correctly overall (33% to 36% of the chi1+2
      angles). Interestingly, when the inter-side-chain interactions were disregarded,
      the mean accuracy increased. A consensus approach is described, in which side
      chain conformations are defined based on the most frequently predicted chi angles
      for a given method upon each set of near-native backbones. We find that consensus
      modeling, which de facto includes backbone flexibility, improves side-chain
      prediction: chi1 accuracy improved to 51-54% (36-42% of chi1+2). Implications of
      a consensus method for ab initio protein structure prediction are discussed.

PMID- 9779789
TI  - Left-handed polyproline II helix formation is (very) locally driven.
AB  - The left-handed polyproline II helix (PPII) is believed to be the preferred
      conformation for proline-rich regions of sequence in proteins. Such regions have
      been postulated to be protein-protein interaction domains. The formation of this
      structure is studied here using simple Monte Carlo computer simulations employing
      the hard sphere potential. It is found that polyproline sequences adopt only the
      PPII structure in the simulations. Non-proline, non-glycine residues inserted as
      guests into polyproline host peptides are conformationally restricted by the
      following proline residues and tend to be part of the PPII helix. It is found
      through insertion of two alanine residues into polyproline that the PPII
      structure is not propagated through more than one non-proline residue. This
      finding calls into question the hypothesis that proline-rich regions will
      preferentially adopt this structure since many such sequences are comprised of
      less than 50% proline residues.

PMID- 9779790
TI  - Exploring the conformational space of protein side chains using dead-end
      elimination and the A* algorithm.
AB  - We describe an algorithm which enables us to search the conformational space of
      the side chains of a protein to identify the global minimum energy combination of
      side chain conformations as well as all other conformations within a specified
      energy cutoff of the global energy minimum. The program is used to explore the
      side chain conformational energy surface of a number of proteins, to investigate
      how this surface varies with the energy model used to describe the interactions
      within the system and the rotamer library. Enumeration of the rotamer
      combinations enables us to directly evaluate the partition function, and thus
      calculate the side chain contribution to the conformational entropy of the folded
      protein. An investigation of these conformations and the relationships between
      them shows that most of the conformations near to the global energy minimum arise
      from changes in side chain conformations that are essentially independent; very
      few result from a concerted change in conformation of two or more residues. Some
      of the limitations of the approach are discussed.

PMID- 9779791
TI  - Tertiary structure prediction of mixed alpha/beta proteins via energy
      minimization.
AB  - We describe an improved algorithm for protein structure prediction, assuming that
      the location of secondary structural elements is known, with particular focus on
      prediction for proteins containing beta-strands. Hydrogen bonding terms are
      incorporated into the potential function, supplementing our previously developed
      residue-residue potential which is based on a combination of database statistics
      and an excluded volume term. Two small mixed alpha/beta proteins, 1-CTF and BPTI,
      are studied. In order to obtain native-like structures, it is necessary to allow
      the beta-strands in BPTI to distort substantially from an ideal geometry, and an
      automated algorithm to carry this out efficiently is presented. Simulated
      annealing Monte Carlo methods, which contain a genetic algorithm component as
      well, are used to produce an ensemble of low-energy structures. For both
      proteins, a cluster of structures with low RMS deviation from the native
      structure is generated and the energetic ranking of this cluster is in the top 2
      or 3 clusters obtained from simulations. These results are encouraging with
      regard to the possibility of constructing a robust procedure for tertiary folding
      which is applicable to beta-strand containing proteins.

PMID- 9779792
TI  - Identification of functional and unfolding motions of cutinase as obtained from
      molecular dynamics computer simulations.
AB  - The implementation of cutinase from Fusarium solani pisi as a fat-stain removing
      ingredient in laundry washing is hampered by its unfolding in the presence of
      anionic surfactants. In this work we present molecular dynamics (MD) computer
      simulations on cutinase and analysis procedures to distinguish the movements
      related to its functional behavior (e.g., substrate binding) from those related
      to the unfolding of the enzyme. Two kinds of MD-simulations were performed: a
      simulation mimicking the thermal motion at room temperature, and several
      simulations in which unfolding is induced either by high temperature or by using
      a modified water-protein interaction potential. Essential dynamics analyses (A.
      Amadei et al., Proteins 17:412-425, 1993) on the simulations identify distinct
      regions in the molecular structure of cutinase in which the motions occur for
      function and initial unfolding. The unfolding in various simulations starts in a
      similar way, suggesting that mutations in the regions involved might stabilize
      the enzyme without affecting its functionality.

PMID- 9779793
TI  - Molecular dynamics study of calbindin D9k in the apo and singly and doubly
      calcium-loaded states.
AB  - Molecular dynamics simulations based on detailed atomic models are used to
      examine the structure and dynamics of calbindin D9k, a protein possessing a pair
      of EF-hands able to bind two calcium ions in a cooperative fashion. Trajectories
      for the apo and singly (in the C-terminal binding site) and doubly loaded
      structures are generated and analyzed. Each system is solvated in a 27 A radius
      sphere of 2,285 explicit water molecules. The influence of the remaining bulk is
      incorporated through a stochastic boundary potential including a solvent reaction
      field. Long-range electrostatic interactions are treated with a special method
      and are not truncated. The average structural and dynamic properties upon calcium
      binding are studied at the atomic level to gain insight into the cooperative
      interactions between the two binding sites. Results from the trajectories are
      compared with data from nuclear magnetic resonance (NMR) spectroscopy and X-ray
      crystallography. NMR 15N and 13C(alpha) backbone relaxation order parameters and
      crystallographic B-factors are calculated. Generally, there is a good qualitative
      agreement between calculated and observed properties. Results confirm that the
      doubly loaded state is closer, both structurally and dynamically, to the singly
      loaded state than either of these is to the apo state. It is observed that both
      hydrogen bonding and the packing of nonpolar side chains contribute to the
      coupling between the calcium binding sites. Two backbone-to-backbone hydrogen
      bonds linking the calcium-binding EF-hands (Leu23-0 ... HN-Val61 and Val61-O ...
      HN-Leu23) are sensitive to the state of occupancy. Residues Leu23 and Val61
      exhibit the smallest rms fluctuations of the entire protein in the D state. In
      addition, the van der Waals interaction of Val61 with the rest of the protein
      varies with the calcium-binding state.

PMID- 9779794
TI  - Structure and dynamic properties of the single disulfide-deficient alpha-amylase
      inhibitor [C45A/C73A]tendamistat: an NMR study.
AB  - Covalent linkages such as disulfide bonds are important for the stabilization of
      proteins. In the present NMR study we compare the structure and the dynamics of
      the single disulfide-deficient variant C45A/C73A of the alpha-amylase inhibitor
      tendamistat and the wild-type protein, which contains two disulfide bonds (C11
      C27 and C45-C73). Complete proton assignment was achieved by standard homonuclear
      2D techniques for the variant. Chemical shift differences, intra-strand NOE
      effects and protected amide proton were used to compare the connectivity of the
      secondary structure elements of variant and wild-type. Dynamic properties of the
      wild-type protein were studied by 13C(alpha) heteronuclear NOE experiments with
      carbon in natural abundance. 15N isotope labeling was necessary to obtain the
      relaxation parameters of the variant, because of sample degradation. The 15N
      resonance assignment was achieved by a 15N 3D-NOESY-HMQC. Removal of the C45-C73
      bond by the C45A/C73A mutation has no influence upon the beta-barrel structure of
      tendamistat beside very local changes at the mutation site. The relaxation data
      revealed only subtle differences between variant and wild-type on a subnanosecond
      time scale. Only the N-terminus and G62 in the connecting loop between the anti
      parallel beta-sheets showed an increased mobility. The results are discussed in
      respect to thermodynamic stability and the secretion efficiency of tendamistat.

PMID- 9779795
TI  - Predicting structural effects in HIV-1 protease mutant complexes with flexible
      ligand docking and protein side-chain optimization.
AB  - We present a computational approach for predicting structures of ligand-protein
      complexes and analyzing binding energy landscapes that combines Monte Carlo
      simulated annealing technique to determine the ligand bound conformation with the
      dead-end elimination algorithm for side-chain optimization of the protein active
      site residues. Flexible ligand docking and optimization of mobile protein side
      chains have been performed to predict structural effects in the V32I/I47V/V82I
      HIV-1 protease mutant bound with the SB203386 ligand and in the V82A HIV-1
      protease mutant bound with the A77003 ligand. The computational structure
      predictions are consistent with the crystal structures of these ligand-protein
      complexes. The emerging relationships between ligand docking and side-chain
      optimization of the active site residues are rationalized based on the analysis
      of the ligand-protein binding energy landscape.

PMID- 9779796
TI  - Probing the potential glycoprotein binding site of sindbis virus capsid protein
      with dioxane and model building.
AB  - Alphavirus budding from the plasma membrane is initiated by the specific
      interaction of the nucleocapsid with the cytoplasmic domain of the glycoprotein
      E2. It was proposed (Lee et al., Structure 4:531-541, 1996) that binding of the
      capsid protein residues 108 to 110 (the "N-terminal arm" residues) to a
      hydrophobic pocket on the surface of the neighboring capsid protein in the
      crystal structure mimics the binding of the E2 C-terminal residues into this
      pocket. In addition, structural comparisons of wild-type and mutant Sindbis virus
      capsid protein (SCP) and Semliki Forest virus capsid protein suggested that
      budding is associated with a switch between two conformations of the hydrophobic
      pocket. To test the proposed mechanism, SCP(114-264), which is missing the N
      terminal arm, was crystallized to examine the pocket conformation when the pocket
      is empty. However, the pocket was occupied by dioxane molecules from the
      crystallization solution. The pocket conformation was the same as that when it
      was occupied by the N-terminal arm, demonstrating that the pocket favors binding
      ligands of appropriate size and shape.

PMID- 9779798
TI  - Hand development in trisomy 21.
AB  - The purpose of the present study was to evaluate hand size and maturity in
      fetuses with trisomy 21 (Down syndrome). Twenty-five fetuses, crown-rump length
      (CRL) 55-222 mm, foot length (FL) 8-42 mm, were included in the study. After
      whole-body radiography (Hewlett Packard Faxitron), special radiographs of the
      hand and foot were taken. Hand length was measured as the length of the third
      finger from the distal tip of the distal phalanx to the proximal tip of the
      metacarpal bone, the digital-metacarpal length (DML). The lengths of the proximal
      phalangeal bone (PPL) and the metacarpal bone (MCL) of the third finger were also
      measured. The DML, PPL, and MCL values of each fetus were related to CRL and FL.
      The individual hand bones were evaluated with regard to time of appearance on
      radiographs, sequence in comparison with the normal sequence of appearance, and
      morphology. The hand length is normal during the first half of the fetal period,
      whereas the length of individual bones in the third finger is reduced. The normal
      sequence of ossification, with the middle phalanx of the fifth finger last to
      ossify, also occurred in Down syndrome; however, this bone appeared later in Down
      syndrome. In four of the fetuses it did not appear.

PMID- 9779797
TI  - First African-American child with juvenile neuronal ceroid lipofuscinosis.
AB  - The neuronal ceroid lipofuscinoses are among the most common forms of progressive
      neurodegenerative disease of childhood. They appear to be panethnic, but there is
      a special predilection of the infantile subtype in Finland. In the United States,
      the Batten disease registry of 731 cases shows that juvenile neuronal ceroid
      lipofuscinosis (JNCL) is the most common form. Here, we report on the first known
      African-American child with JNCL. Genetic study showed the 1.02-kb deletion
      typically seen in JNCL cases.

PMID- 9779799
TI  - Rapp-Hodgkin syndrome with palmoplantar keratoderma, glossy tongue, congenital
      absence of lingual frenum and of sublingual caruncles: newly recognized findings.
AB  - We report on a boy with Rapp-Hodgkin syndrome (RHS) or Rapp-Hodgkin ectodermal
      dysplasia. He had sparse, wiry, slow growing and uncombable hair, but no pili
      torti or pili canaliculi characteristic of RHS. He also had sparse eyelashes and
      eyebrows, and obstructed lacrimal puncta and epiphora. Bilateral bony external
      auditory canal stenosis led to hearing loss. The mouth was small with repaired
      bilateral cleft lip and palate. Oral manifestations included hypodontia,
      microdontia, unerupted mandibular premolars with well formed roots, large dental
      pulp spaces, enamel hypoplasia, multiple caries, glossy tongue, and congenital
      absence of lingual frenum and of sublingual caruncles including submandibular and
      sublingual salivary duct openings. Palmo-plantar keratoderma, unerupted
      premolars, congenital absence of lingual frenum, sublingual caruncles, glossy
      tongue, and pili canaliculi seen in the patient are newly recognized findings of
      this syndrome. Overlapping findings of RHS ectrodactyly-ectodermal dysplasia
      clefting syndrome (EEC), and ankyloblepharon-ectodermal defects-cleft lip and
      palate syndrome (AEC) are discussed.

PMID- 9779800
TI  - Seven cases of Wiedmann-Beckwith syndrome, including the first reported case of
      mosaic paternal isodisomy along the whole chromosome 11.
AB  - Genomic imprinting of chromosome arm 11p is involved in the Wiedemann-Beckwith
      syndrome (WBS). About 20% of patients with sporadic WBS have paternal uniparental
      disomy (UPD) of 11p. Mitotic recombination at the 11p region has been suggested
      to be responsible for the somatic mosaicism in these patients. Our current study
      concerning sporadic WBS patients demonstrated six patients with mosaic isodisomy
      restricted to part of 11p and one patient with mosaic paternal uniparental disomy
      for the whole chromosome 11. Apparently the clinical findings for this patient
      did not differ from data reported for other WBS patients. This case makes it
      unlikely that the proximal short arm and the long arm of chromosome 11 contain
      imprinted genes with a phenotype recognizable prenatally or in infancy, and gives
      some support to the hypothesis that non-mosaic UPD-11 is prenatally lethal.

PMID- 9779801
TI  - Hereditary febrile seizures: phenotype and evidence for a chromosome 19p locus.
AB  - The occurrence of febrile seizures (FSs) in large autosomal dominant FS kindreds
      makes possible accurate delineation of the pure clinical phenotype of hereditary
      FS among secondary FS cases, and the identification of gene loci causing
      susceptibility to FS. Recently FS gene loci on chromosomes 8 and 19 were
      identified. We studied the phenotype of FS in four large families in which FS is
      an autosomal dominant trait. Among 30 affected secondary FS cases, mean age of
      onset was 16.3 months (range 4 to 36 months), sex ratio was equal, and 43% were
      complex (13 of 30). Among these 30 secondary FS cases, the mean number of FSs was
      2.1, half had only a single FS, and none had afebrile seizures. Penetrance was
      0.67, approximately the same as in our previous larger group of 40 multicase FS
      families (0.64). The occurrence of DPT encephalopathy in a sib of a patient with
      FS raises the possibility that these two etiologies are related. Linkage studies
      showed that one of the four families (Family 1) was linked to chromosome 19p
      markers, none of the families was linked to chromosome 8q markers, and the
      largest FS family (Kindred 6) was unlinked to either 19p or 8q markers,
      supporting the hypothesis of genetic heterogeneity for FS.

PMID- 9779802
TI  - Three cases of mosaicism for balanced reciprocal translocations.
AB  - Mosaicism for a balanced reciprocal translocation (BRTM) is rare. As far as we
      know only 26 cases of BRTM, demonstrated in lymphocyte cultures, have been
      described, five of which had an abnormal phenotype. Prenatally three confirmed
      cases with a normal phenotypic outcome have been described. Here we present three
      further cases of BRTM in lymphocyte cultures. The first was detected during a
      family study, the second after an abnormal karyotype in chorionic villus
      sampling, and the third because of a history of stillborn children. All three
      carriers have normal phenotypes. An inventory of the BRTM cases reported so far
      is made.

PMID- 9779804
TI  - Methylmalonic aciduria (cblF): case report and response to therapy.
AB  - Methylmalonic acidemia can be secondary to a deficiency of methylmalonyl CoA
      mutase or to a defect of cobalamin metabolism that is classified by
      complementation group. We report on a new patient with cblF complementation group
      that is associated with an elevation of both methylmalonic acid and homocysteine,
      and her outcome in response to routine therapy and a dietary restriction.

PMID- 9779803
TI  - Systematic search for uniparental disomy in early fetal losses: the results and a
      review of the literature.
AB  - About 20% of all human conceptuses are estimated to be trisomic and trisomy of
      all chromosomes remains a common cause of early fetal loss. Uniparental disomy
      (UPD) has been reported for most human chromosomes and may be an underrecognized
      contributor to embryonic lethality. To investigate the contribution of UPD to
      spontaneous abortions, we devised a genome-based screening strategy to identify
      holochromosomic UPD in 18 fetal losses. No cases of UPD were identified using
      this approach. Based on our data, UPD does not appear to be a significant
      contributor to early embryonic lethality. The results of the study are presented
      along with a review of the cases of UPD reported in the literature by chromosome,
      parental origin, mode of ascertainment, and phenotypic consequences due to
      imprinting.

PMID- 9779805
TI  - International nomenclature and classification of the osteochondrodysplasias
      (1997). International Working Group on Constitutional Diseases of Bone.

PMID- 9779806
TI  - Spinocerebellar ataxia type 2 (SCA 2) in an infant with extreme CAG repeat
      expansion.
AB  - Autosomal dominant cerebellar ataxias are a heterogeneous group of
      neurodegenerative disorders that generally present in adulthood. Spinocerebellar
      ataxia type 2 typically presents with progressive cerebellar symptoms, slow
      ocular saccades, and peripheral neuropathy. The onset of symptoms is usually
      between 20 and 40 years. We describe an infant who presented with neonatal
      hypotonia, developmental delay, and dysphagia. Ocular findings of retinitis
      pigmentosa were noted at 10 months. Her father had mild spinocerebellar ataxia
      first noted at age 22 years. Molecular studies of the SCA2 gene showed a CAG
      expansion of 43 repeats in the father and an extreme CAG repeat expansion of more
      than 200 in the baby. Our report expands the known phenotype and genotype of
      SCA2. Testing for dominant ataxias should be included in the evaluation of
      infants with nonspecific progressive neurologic symptoms and retinitis
      pigmentosa, especially in cases with a positive family history for
      spinocerebellar ataxia.

PMID- 9779807
TI  - Hearing loss due to the mitochondrial A1555G mutation in Italian families.
AB  - Six Italian families with familial nonsyndromic hearing loss consistent with a
      maternal pattern of inheritance were analyzed for mitochondrial mutations. The
      three known mitochondrial mutations associated with nonsyndromic hearing loss
      were investigated by polymerase chain reaction amplification, followed by
      restriction fragment length analysis or DNA sequencing. The A7445G mutation and
      C7472 insertion were not present in either of the families, but the A1555G
      mutation in the 12S rRNA gene was identified in homoplasmic form in two of the
      families. In one of the families the onset of hearing loss is congenital, while
      in the other it starts later in life. The families are from different regions of
      Italy, and mitochondrial haplotype analysis showed that the mutation arose
      independently in these two families. This suggests that the A1555G mutation may
      not be an uncommon cause of hearing loss in Italians, and is clinically important
      because maternal hearing relatives of patients with the A1555G mutation are at
      risk for aminoglycoside induced deafness. We discuss potential reasons for the
      normal phenotype in some relatives with the mutation, and the different onset of
      hearing loss in the two families.

PMID- 9779808
TI  - Prenatal ultrasonographic description and postnatal pathological findings in
      atelosteogenesis type 1.
AB  - Atelosteogenesis type 1 (AO1) is a rare lethal chondrodysplasia characterized by
      incomplete ossification of cartilage anlagen. Histologically, the cartilage
      contains irregular clusters that occasionally include giant chondrocytes.
      Pulmonary hypoplasia is a characteristic finding that has been presumed to be the
      cause of neonatal lethality. We report on a male fetus with AO1 and document the
      early ultrasonographic/ radiologic progression of this disorder from 15 weeks
      gestation until delivery at 41 weeks. While the radiological findings we describe
      are typical of AO1 by the lack of proximal and middle phalangeal ossification,
      the complete radiological picture showed considerable overlap with boomerang
      dysplasia. Although pulmonary hypoplasia was present, it was moderate and
      considered unlikely to be the sole cause of death. Detailed neonatal and
      postmortem examination showed severe subglottic hypoplasia and tracheomalacia.
      The tracheal walls were supported by thin and pliable cartilaginous plates that
      allowed luminal collapse with minimal pressure. The marked luminal narrowing,
      tracheomalacia, and temporal proximity of extubation to demise support tracheal
      collapse as a major contributor to the death in AO1. The detailed description of
      this patient should contribute to earlier diagnosis of this condition;
      anticipation of the poor prognosis in AO1 is essential for appropriate genetic
      counseling of the parents and for determining postnatal treatment options.

PMID- 9779809
TI  - Identification of a missense mutation in a Friedreich's ataxia patient:
      implications for diagnosis and carrier studies.
AB  - Approximately 95% of all Friedreich's ataxia (FA) patients are homozygous for a
      large GAA triplet-repeat expansion in the first intron of the Friedreich's ataxia
      gene (FRDA). The remaining cases are expected to be compound heterozygous with a
      GAA expansion on one allele and a point mutation on the other. Generally, the
      clinical diagnostic profile in this group of patients is indistinguishable from
      that in classic FA patients with homozygous expansions. This study describes a
      mildly affected patient who presents with only one expanded allele by Southern
      blot analysis. Point mutation screening shows a single base change in FRDA exon 3
      resulting in a nonconservative amino acid replacement in the N-terminal portion
      of the frataxin protein. Extended family studies show that two of the patient's
      sibs are carriers of the expanded allele and one is a carrier of the missense
      mutation. This case study demonstrates the benefits of implementing a combined
      Southern blot and point mutation diagnostic protocol for compound heterozygous
      patients. By identifying both mutations, this procedure confirms the diagnosis of
      FA in patients with an atypical disease course and allows for more complete
      family studies.

PMID- 9779810
TI  - Further evidence of autosomal dominant inheritance of the nonsyndromal anorectal
      malformations.

PMID- 9779811
TI  - Hypoplasia of the transverse sinus in oto-palato-digital syndrome type I.

PMID- 9779812
TI  - Confounding factors in the diagnosis of Fanconi anaemia.

PMID- 9779813
TI  - Seven new cases of Cayler cardiofacial syndrome with chromosome 22q11.2 deletion,
      including a familial case.

PMID- 9779814
TI  - Expression of alpha2-macroglobulin receptor-associated protein in normal human
      epidermal melanocytes and human melanoma cell lines.
AB  - Alpha2-Macroglobulin receptor/low-density lipoprotein receptor-related protein is
      a multifunctional cell surface receptor known to bind and internalize a large
      number of ligands. alpha2-Macroglobulin receptor-associated protein acts as an
      intracellular "chaperone" for this receptor, and it has been shown to inhibit
      binding of all its known ligands. In this paper, we characterize the expression
      of the receptor-associated protein in both normal human epidermal melanocytes and
      in six different human melanoma cell lines, by the use of flow cytometry and
      Western blotting analysis. We show that all the melanoma cell lines and the
      normal melanocytes express the receptor-associated protein at similar levels,
      with most located intracellularly. No receptor-associated protein was detected at
      the cell surface in the melanocytes or in three of the cell lines. However, in
      two of the melanoma cell lines, large amounts of receptor-associated protein were
      found on the cell surface, these having the largest amounts of it reported to
      date; in a further melanoma cell line, there was a small amount at the cell
      surface. We have also shown that the melanocytes and all the melanoma cell lines
      express the receptor itself at a wide range of levels, the highest levels of both
      the cell surface receptor and the cell surface receptor-associated protein being
      found in one particular melanoma cell line. By growing the cell lines under
      controlled conditions, we have demonstrated that, although the total cellular
      content of the receptor is markedly increased at high cell culture density, this
      treatment has no effect on the level of expression of the receptor-associated
      protein.

PMID- 9779816
TI  - Identification of mitogen-activated protein kinase-activated protein kinase-2 as
      a vimentin kinase activated by okadaic acid in 9L rat brain tumor cells.
AB  - Organization of intermediate filament, a major component of cytoskeleton, is
      regulated by protein phosphorylation/dephosphorylation, which is a dynamic
      process governed by a balance between the activities of involved protein kinases
      and phosphatases. Blocking dephosphorylation by protein phosphatase inhibitors
      such as okadaic acid (OA) leads to an apparent activation of protein kinase(s)
      and to genuine activation of phosphatase-regulated protein kinase(s). Treatment
      of 9L rat brain tumor cells with OA results in a drastically increased
      phosphorylation of vimentin, an intermediate filament protein. In-gel renaturing
      assays and in vitro kinase assays using vimentin as the exogenous substrate
      indicate that certain protein kinase(s) is activated in OA-treated cells. With
      specific protein kinase inhibitors, we show the possible involvement of the cdc2
      kinase- and p38 mitogen-activated protein kinase (p38MAPK)-mediated pathways in
      this process. Subsequent in vitro assays demonstrate that vimentin may serve as
      an excellent substrate for MAPK-activated protein kinase-2 (MAPKAPK-2), the
      downstream effector of p38MAPK, and that MAPKAPK-2 is activated with OA
      treatment. Comparative analysis of tryptic phosphopeptide maps also indicates
      that corresponding phosphopeptides emerged in vimentin from OA-treated cells and
      were phosphorylated by MAPKAPK-2. Taken together, the results clearly demonstrate
      that MAPKAPK-2 may function as a vimentin kinase in vitro and in vivo. These
      findings shed new light on the possible involvement of the p38MAPK signaling
      cascade, via MAPKAPK-2, in the maintenance of integrity and possible
      physiological regulation of intermediate filaments.

PMID- 9779815
TI  - Lysosomal segregation of a mannose-rich glycoprotein imparted by the prosequence
      of myeloperoxidase.
AB  - The role of the N-terminal sequence of myeloperoxidase in the intracellular
      targeting was examined by using glycosylated lysozyme as a reporter. A fusion
      protein was constructed in which the presequence residues-18 through -6 of the
      lysozyme moiety had been replaced by residues 1-158 of prepromyeloperoxidase.
      Expression of the fusion protein in Chinese hamster ovary cells demonstrated its
      partial secretion and partial intracellular retention. The latter was accompanied
      by trimming the myeloperoxidase prosequence off the lysozyme moiety. The rate of
      the retention of the lysozyme fusion protein was higher than that of glycosylated
      lysozyme that had been expressed in cells transfected with cDNA of glycosylated
      lysozyme. The retention was insensitive to NH4Cl. In the secreted protein,
      lysozyme contained predominantly complex oligosaccharides as demonstrated by a
      proteolytic fragmentation in vitro and resistance to endo-beta-N
      acetylglucosaminidase H. In contrast, when targeted to lysosomes, the lysozyme
      moiety of the fusion protein contained predominantly mannose-rich
      oligosaccharides. In baby hamster kidney cells, the trimming of the
      oligosaccharides in the lysozyme fragment was less vigorous, and a selective
      targeting of molecules bearing mannose-rich oligosaccharides to lysosomes was
      more apparent than in Chinese hamster ovary cells. In the presence of monensin,
      the formation of complex oligosaccharides in the fusion protein and its secretion
      were strongly inhibited, whereas the intracellular fragmentation was not. We
      suggest that the prosequence of myeloperoxidase participates in the intracellular
      routing of the precursor and that this routing operates on precursors bearing
      mannose-rich rather than terminally glycosylated oligosaccharides and diverts
      them from the secretory pathway at a site proximal to the monensin-sensitive
      compartment of the Golgi apparatus.

PMID- 9779817
TI  - Characterization of sulfonylurea receptors in isolated human pancreatic islets.
AB  - Current information on pancreatic islet sulfonylurea receptors has been obtained
      with laboratory animal pancreatic beta cells or stable beta-cell lines. In the
      present study, we evaluated the properties of sulfonylurea receptors of human
      islets of Langherans, prepared by collagenase digestion and density-gradient
      purification. The binding characteristics of labeled glibenclamide to pancreatic
      islet membrane preparations were analyzed, displacement studies with several oral
      hypoglycemic agents were performed, and these latter compounds were tested as for
      their insulinotropic action on intact human islets. [3H]glibenclamide saturable
      binding was shown to be linear at < or =0.25 mg/ml protein; it was both
      temperature and time dependent. Scatchard analysis of the equilibrium binding
      data at 25 degrees C indicated the presence of a single class of saturable, high
      affinity binding sites with a Kd value of 1.0+/-0.07 nM and a Bmax value of 657+/
      48 fmol/mg of proteins. The displacement experiments showed the following rank
      order of potency of the oral hypoglycemic agents we tested: glibenclamide =
      glimepiride > tolbutamide > chlorpropamide >> metformin. This binding potency
      order was parallel with the insulinotropic potency of the evaluated compounds.

PMID- 9779818
TI  - Hexose transporter expression and function in mammalian spermatozoa: cellular
      localization and transport of hexoses and vitamin C.
AB  - We analyzed the expression of hexose transporters in human testis and in human,
      rat, and bull spermatozoa and studied the uptake of hexoses and vitamin C in bull
      spermatozoa. Immunocytochemical and reverse transcription-polymerase chain
      reaction analyses demonstrated that adult human testis expressed the hexose
      transporters GLUT1, GLUT2, GLUT3, GLUT4, and GLUT5. Immunoblotting experiments
      demonstrated the presence of proteins of about 50-70 kD reactive with anti-GLUT1,
      GLUT2, GLUT3, and GLUT5 in membranes prepared from human spermatozoa, but no
      proteins reactive with GLUT4 antibodies were detected. Immunolocalization
      experiments confirmed the presence of GLUT1, GLUT2, GLUT3, GLUT5, and low levels
      of GLUT4 in human, rat, and bull spermatozoa. Each transporter isoform showed a
      typical subcellular localization in the head and the sperm tail. In the tail,
      GLUT3 and GLUT5 were present at the level of the middle piece in the three
      species examined, GLUT1 was present in the principal piece, and the localization
      of GLUT2 differed according of the species examined. Bull spermatozoa transported
      deoxyglucose, fructose, and the oxidized form of vitamin C, dehydroascorbic acid.
      Transport of deoxyglucose and dehydroascorbic acid was inhibited by cytochalasin
      B, indicating the direct participation of facilitative hexose transporters in the
      transport of both substrates by bull spermatozoa. Transport of fructose was not
      affected by cytochalasin B, which is consistent for an important role for GLUT5
      in the transport of fructose in these cells. The data show that human, rat, and
      bull spermatozoa express several hexose transporter isoforms that allow for the
      efficient uptake of glucose, fructose, and dehydroascorbic acid by these cells.

PMID- 9779820
TI  - Role of the pro-alpha2(I) COOH-terminal region in assembly of type I collagen:
      truncation of the last 10 amino acid residues of pro-alpha2(I) chain prevents
      assembly of type I collagen heterotrimer.
AB  - Procollagen (Type I) contains a noncollagenous COOH-terminal propeptide (C
      propeptide) hypothesized to be important in directing chain association and
      alignment during assembly. We previously expressed human pro-alpha2(I) cDNA in
      rat liver epithelial cells, W8, that produce only pro-alpha1(I) trimer collagen
      (Lim et al. [1994] Matrix Biol. 14: 21-30). In the resulting cell lines,
      alpha2(I) assembled with alpha1(I) forming heterotrimers. Using this cell system,
      we investigated the importance of the COOH-terminal propeptide sequence of the
      pro-alpha2(I) chain for normal assembly of type I collagen. Full-length human pro
      alpha2(I) cDNA was cloned into expression vectors with a premature stop signal
      eliminating the final 10 amino acids. No triple-helical molecules containing
      alpha2(I) were detected in transfected W8 cells, although pro-alpha2(I) mRNA was
      detected. Additional protein analysis demonstrated that these cells synthesize
      small amounts of truncated pro-alpha2(I) chains detected by immunoprecipitation
      with a pro-alpha2(I) antibody. In addition, since the human-rat collagen was less
      thermostable than normal intraspecies collagen, wild-type and C-terminal
      truncated mouse cDNAs were expressed in mouse D2 cells, which produced only type
      I trimers. Results from both systems were consistent, suggesting that the last 10
      amino acid residues of the pro-alpha2(I) chain are important for formation of
      stable type I collagen.

PMID- 9779819
TI  - Spectrin localization in osteoclasts: immunocytochemistry, cloning, and partial
      sequencing.
AB  - The presence of spectrin was demonstrated in chick osteoclasts by Western
      blotting and light and electron microscopic immunolocalization. Additionally,
      screening of a chick osteoclast cDNA library revealed the presence of alpha
      spectrin. Light microscope level immunocytochemical staining of osteoclasts in
      situ revealed spectrin staining throughout the cytoplasm with heavier staining
      found at the marrow-facing cell margin and around the nuclei. Confocal microscopy
      of isolated osteoclasts plated onto a glass substrate showed that spectrin
      encircled the organelle-rich cell center. Nuclei and cytoplasmic inclusions were
      also stained and the plasma membrane was stained in a nonuniform, patchy
      distribution corresponding to regions of apparent membrane ruffling.
      Ultracytochemical localization showed spectrin to be found at the plasma membrane
      and distributed throughout the cytoplasm with especially intense staining of the
      nuclear membrane and filaments within the nuclear compartment.

PMID- 9779822
TI  - Level of HgCl2-mediated phosphorylation of intracellular proteins determines
      death of thymic T-lymphocytes with or without DNA fragmentation.
AB  - Exposure to Hg2+ at a wide range of concentrations (approximately 1-100 microM)
      more or less caused the death of murine thymic T-lymphocytes, and exposure to 1
      microM but not 10 microM (or more) of Hg2- induced DNA fragmentation. Exposure of
      cells to Hg2+ caused phosphorylation of multiple cellular proteins at the
      tyrosine residue in a concentration-dependent manner. We found that not only the
      DNA fragmentation induced by 1 microM Hg2+ but also the cell death bypassing DNA
      fragmentation caused by 10 microM or more Hg2+ was partly inhibited by protein
      kinase inhibitors such as staurosporine and herbimycin A. This result suggested
      the involvement of a protein phosphorylation-linked signal in the mechanism of
      the Hg2+-mediated cell death with or without DNA fragmentation. Analysis of
      proteins by both one- and two-dimensional electrophoresis and immunoblot showed
      that a 52-kDa Shc protein was heavily phosphorylated by an early signal delivered
      by a high concentration of Hg2+, which also phosphorylated extracellular signal
      regulated kinase 1 (ERK1; p44) and ERK2 (p42) of the mitogen-activated protein
      kinase (MAPK) family in a concentration- and time-dependent manner. The c-Jun
      amino terminal kinase (p54), which is a distant relative of the MAPK family, was
      also phosphorylated by the treatment with Hg2+. This eventually formed the
      signaling cascade that ended with a nuclear target by phosphorylating c-jun at
      the serine 73. This phosphorylation of c-jun was inhibited by staurosporine.
      These results suggest that a high level of Hg2+-mediated protein phosphorylation
      linked signal induces rapid cell death bypassing DNA fragmentation, whereas a
      lower level induces cell death accompanying DNA fragmentation. This conclusion in
      turn implies that DNA fragmentation is not always a prerequisite for the signal
      transduction-dependent cell death of T-lymphocytes.

PMID- 9779821
TI  - Role of the pro-alpha2(I) COOH-terminal region in assembly of type I collagen:
      disruption of two intramolecular disulfide bonds in pro-alpha2(I) blocks assembly
      of type I collagen.
AB  - Collagen biosynthesis is a complex process that begins with the association of
      three procollagen chains. A series of conserved intra- and interchain disulfide
      bonds in the carboxyl-terminal region of the procollagen chains, or C-propeptide,
      has been hypothesized to play an important role in the nucleation and alignment
      of the chains. We tested this hypothesis by analyzing the ability of normal and
      cysteine-mutated pro-alpha2(I) chains to assemble into type I collagen
      heterotrimers when expressed in a cell line (D2) that produces only endogenous
      pro-alpha1(1). Pro-alpha2(I) chains containing single or double cysteine
      mutations that disrupted individual intra- or interchain disulfide bonds were
      able to form pepsin resistant type I collagen with pro-alpha1(I), indicating that
      individual disulfide bonds were not critical for assembly of the pro-alpha2(I)
      chain with pro-alpha1(I). Pro-alpha2(I) chains containing a triple cysteine
      mutation that disrupted both intrachain disulfide bonds were not able to form
      pepsin resistant type I collagen with pro-alpha1(I). Therefore, disruption of
      both pro-alpha2(I) intrachain disulfide bonds prevented the production and
      secretion of type I collagen heterotrimers. Although none of the individual
      disulfide bonds is essential for assembly of the procollagen chains, the presence
      of at least one intrachain disulfide bond may be necessary as a structural
      requirement for chain association or to stabilize the protein to prevent
      intracellular degradation.

PMID- 9779823
TI  - Role of EP2 receptors and cAMP in prostaglandin E2 regulated expression of type I
      collagen alpha1, lysyl oxidase, and cyclooxygenase-1 genes in human embryo lung
      fibroblasts.
AB  - In a recent communication, we demonstrated that prostaglandin E2 (PGE2) lowers
      basal while it ablates interleukin-1beta((IL-1beta) and transforming growth
      factor-beta (TGFbeta) upregulated lysyl oxidase (LO) mRNA levels.
      Correspondingly, PGE2 increases cyclooxygenase-1 (COX1) mRNA in diploid, human
      embryo lung fibroblasts (IMR90) [Roy et al., 19961. We now report that these
      actions by PGE2 are routed through cAMP via the PGE2, EP2 receptor. Among the
      PGE2 receptor types, the IMR90 predominantly express the EP2 mRNA. These cells
      also express EP3 and EP4 mRNA at comparatively low levels. Northern blot analyses
      show that 11-deoxy PGE1, an EP2/EP4 agonist, emulates the action of PGE2. In a
      similar manner to PGE2, 11-deoxy PGE1 decreases basal and TGF-beta induced type I
      collagen alpha1 (COL) mRNA, basal and IL-1beta induced LO mRNA while it increases
      COX1 mRNA. Sulprostone, an EP3/EP1 agonist, has no effect on the expression of
      these three genes. Forskolin, an adenylate cyclase activator, acts in a very
      similar manner to PGE2 or 11-deoxy PGE1. It suppresses both basal and TGF-beta
      induced COL mRNA levels. Both PGE2 and 11-deoxy PGE1 increase cAMP to a level
      comparable with forskolin. The role of the EP2 receptor in controlling collagen
      production is further underscored in the immortalized Rat-1 fibroblasts, derived
      from Fischer rat embryos, which do not express detectable EP2 mRNA. In these
      cells, PGE2 has little effect on COL mRNA level, whereas forskolin increases it.
      Furthermore, forskolin increases cAMP level in Rat-1 cells, whereas PGE2 does
      not. Overall, these results illustrate that much of the PGE2 action on the
      expression of COL, LO, and COX1 genes is mediated through the EP2 receptor and a
      subsequent increase in intracellular cAMP.

PMID- 9779824
TI  - Hepatocyte growth factor/scatter factor and hepatocytes are potent downregulators
      of tyrosinase expression in B16 melanoma cells.
AB  - Reiterated selection in vivo of B16 murine melanoma cells for enhanced liver
      metastatic ability yielded a cel line (B16-LS9) dramatically overexpressing a
      constitutively active hepatocyte growth factor/scatter factor (HGF/SF) receptor,
      the product of the c-met proto-oncogene. Most likely because of their
      overexpressing c-met, B16-LS9 cells appear to be more responsive than parental
      B16-F1 cells to HGF stimulation, in terms of motility, invasion, and growth. They
      are also more pigmented, and express higher levels of tyrosinase as compared to
      parental B1 6-F1 cells. Therefore, we set out to explore whether HGF/SF and the
      liver might influence the differentiation state of B1 6 cells. We found that
      HGF/SF and MSH, two factors which reportedly have a strong influence on the
      phenotype and the malignant behavior of melanoma cells, may act at different
      levels, and with opposite results, on the regulation of gene expression. In fact,
      while MSH induces, at the transcriptional level, an increase in the production of
      both c-met and tyrosinase, HGF/SF, in contrast, promotes a decrease in the
      expression of both c-met and tyrosinase, however at a posttranscriptional level.
      These two opposite effects can counter-balance each other, when the cells are
      treated with both factors at the same time, apparently through a mechanism
      involving MAP kinase activation. The effects were, however, additive when
      morphological changes were considered. Most intriguingly, we also describe a very
      strong downregulatory activity, limited to tyrosinase expression, by hepatocytes
      in coculture with B16 cells. This activity, also at the posttranscriptional
      level, is much stronger than that exerted by HGF/SF, and appears to be due to a
      labile soluble factor produced by the hepatocytes.

PMID- 9779825
TI  - Differential expression of Id genes in multipotent myeloid progenitor cells: Id-1
      is induced by early-and late-acting cytokines while Id-2 is selectively induced
      by cytokines that drive terminal granulocytic differentiation.
AB  - Hematopoietic development is regulated by a complex mixture of cytokine growth
      factors that guide growth and differentiation of progenitor cell populations at
      different stages in their development. The genetic programs that drive this
      process are controlled at the molecular level by the type and number of
      transcriptional regulators coexpressed in the cell. Both positive- and negative
      acting helix-loop-helix transcription factors are expressed during hematopoietic
      development, with the Id-type transdominant negative regulators controlling the
      net helix-loop-helix activation potential in the cell at any given time. It has
      been demonstrated that some of these Id factors are involved in the checkpoint at
      which undifferentiated progenitor cells make the commitment to terminal
      maturation. Therefore, we sought to determine whether these Id family factors are
      selectively induced or extinguished by cytokines that act at different points
      during hematopoiesis. NFS-60, a myeloid progenitor line that proliferates in
      response to multiple cytokines, was stimulated by treatment with SCF, IL-3, IL-6,
      G-CSF, and erythropoietin. Id-1 expression correlated tightly with cellular
      proliferation: it declined when growth factor stimulation was withdrawn and was
      quickly induced whenever the cell began to proliferate. The regulation of Id-2
      was more complex: its expression was slightly upregulated in factor-deprived
      cells but only strongly reinduced after extended exposure to cytokines that drive
      granulocytic differentiation (IL-6, G-CSF, and TGFbeta). These data support a
      cell-cycle regulatory role for Id-1 in multipotent myeloid progenitor cells and a
      role for Id-2 during terminal granulocytic differentiation.

PMID- 9779826
TI  - Expression of mitogen-activated protein kinase pathways during postnatal
      development of rat heart.
AB  - The loss of ability to proliferate (terminal differentiation) and reduction in
      capability to resist ischemia are key phenomena observed during postnatal
      development of the heart. Mitogen-activated protein kinases (MAPKs) mediate
      signaling pathways for cell proliferation/differentiation and stress responses
      such as ischemia. In this study, the expression of these kinases and their
      associated kinases were investigated in rat heart ventricle. Extracts of 1-, 10-,
      20-, 50-, and 365-day-old rat heart ventricles were probed with specific
      antibodies and their immunoreactivities were quantified by densitometry. Most of
      the mitogenic protein kinases including Raf1, RafB, Mek1, Erk2, and Rsk1 were
      significantly down-regulated, whereas the stress signaling kinases, such as Mlk3,
      Mekkl, Sekl, Mkk3, and Mapkapk2 were up-regulated in expression during postnatal
      development. Most MAP kinases including Erk1, JNKs, p38 Hog, as well as Rsk2,
      however, did not exhibit postnatal changes in expression. The proto-oncogene
      encoded kinases Mos and Cot/Tpl 2 were up-regulated up to two- and four-fold,
      respectively, during development. Pakl, which may be involved in the regulation
      of cytoskeleton as well as in stress signaling, was downregulated with age, but
      the Pak2 isoform increased only after 50 days. All of these proteins, except
      RafB, were also detected in the isolated adult ventricular myocytes at comparable
      levels to those found in adult ventricle. Tissue distribution studies revealed
      that most of the protein kinases that were up-regulated during heart development
      tended to be preferentially expressed in heart, whereas the downregulated protein
      kinases were generally expressed in heart at relatively lesser amounts than in
      most of other tissues.

PMID- 9779827
TI  - Evidence of a direct role for Bcl-2 in the regulation of articular chondrocyte
      apoptosis under the conditions of serum withdrawal and retinoic acid treatment.
AB  - The regulation of chondrocyte apoptosis in articular cartilage may underlay age
      associated changes in cartilage and the development of osteoarthritis. Here we
      demonstrate the importance of Bcl-2 in regulating articular chondrocyte apoptosis
      in response to both serum withdrawal and retinoic acid treatment. Both stimuli
      induced apoptosis of primary human articular chondrocytes and a rat chondrocyte
      cell line as evidenced by the formation of DNA ladders. Apoptosis was accompanied
      by decreased expression of aggrecan, a chondrocyte specific matrix protein. The
      expression of Bcl-2 was downregulated by both agents based on Northern and
      Western analysis, while the level of Bax expression remained unchanged compared
      to control cells. The importance of Bcl-2 in regulating chondrocyte apoptosis was
      confirmed by creating cell lines overexpressing sense and antisense Bcl-2 mRNA.
      Multiple cell lines expressing antisense Bcl-2 displayed increased apoptosis even
      in the presence of 10% serum as compared to wild-type cells. In contrast,
      chondrocytes overexpressing Bcl-2 were resistant to apoptosis induced by both
      serum withdrawal and retinoic acid treatment. Finally, the expression of Bcl-2
      did not block the decreased aggrecan expression in IRC cells treated with
      retinoic acid. We conclude that Bcl-2 plays an important role in the maintenance
      of articular chondrocyte survival and that retinoic acid inhibits aggrecan
      expression independent of the apoptotic process.

PMID- 9779829
TI  - An in situ nanoindentation specimen holder for a high voltage transmission
      electron microscope.
AB  - We describe in detail, the design, construction, and testing of a specimen holder
      that allows for the nanoindentation of surfaces while viewing in cross-section in
      a high voltage transmission electron microscope (TEM). This nanoindentation
      specimen holder, having three-axis position control of a diamond indenter in
      combination with micromachined specimens, allows for the first time the dynamic
      observation of subsurface microstructure evolution under an indenter tip.
      Additionally, the sample design techniques that have been developed for these
      procedures may eliminate the need for TEM specimen preparation for additional ex
      situ nanoindentation experiments. Initial experimental results from in situ
      indentation of Si samples in the high voltage electron microscope are reported
      here to demonstrate the capability of this new specimen holder.

PMID- 9779828
TI  - In situ measurement of dihedral angles at liquid grain boundary inclusions.
AB  - This work describes experimental aspects of the measurement of relative
      interfacial energies from the equilibrium dihedral angles of small liquid
      inclusions or precipitates at interfaces in solids using in situ transmission
      electron microscopy. We demonstrate how limitations such as faceting, free
      surfaces, and projection errors can be handled to minimize experimental errors.

PMID- 9779831
TI  - Controlled environment transmission electron microscopy.
AB  - The design of a controlled environment electron microscope is described and
      examples are presented to demonstrate the information that can be obtained by
      studying gas-solid interactions in real time and at high spatial resolution.

PMID- 9779830
TI  - In situ transmission electron microscopy employed for studies of effects of ion
      and electron irradiation on materials.
AB  - This paper summarizes the essential features of the various facilities dedicated
      to in situ irradiation effects research around the world at the present time,
      mentions some essential techniques that are involved in this type of research,
      and describes very briefly some examples of studies employing these facilities
      and techniques.

PMID- 9779832
TI  - Development of a TEM to study in situ structural and chemical changes at an
      atomic level during gas-solid interactions at elevated temperatures.
AB  - A Philips (Eindhoven, The Netherlands) 430 (300 keV) high resolution transmission
      electron microscope has been modified for in situ study of gas-solid interactions
      at elevated temperatures. This microscope can be best described as a synthesis,
      processing, and characterization laboratory for nano-size materials. A
      differentially pumped environmental cell (E-cell), capable of handling up to 20
      torr of gas pressure, is fitted in the objective lens pole-piece gap. Single-tilt
      or double-tilt heating holders can be used to heat the samples up to 1,300
      degrees C and 850 degrees C, respectively. The system can handle any non
      corrosive gases such as H2, O2, N2, NH3, CO, water vapor. Electron diffraction
      patterns are used to elucidate the reaction path and to identify stable and/or
      metastable phases formed. Time, temperature, and pressure resolved electron
      diffraction patterns can also be used to estimate the thermodynamical conditions
      for the onset of a reaction and the stability range of different phases observed
      during the process can also be determined. The high resolution imaging
      capabilities enable elucidation of the basic structural mechanisms involved at
      near atomic level. The TV rate camera/video recording system is used to measure
      the reaction rates (kinetics of the reaction). A post projector energy filter
      (Gatan Imaging Filter, GIF) is attached at the bottom of the microscope in order
      to filter the inelastic scattering from the gases/thick samples as well as to
      obtain energy filtered images (chemical maps). The GIF can also be used as a
      parallel electron energy loss spectrometer (PEELS) to obtain changes in the
      sample composition during the reactions. The changes in the near-edge structures
      of PEELS spectrum is used to monitor changes in bonding and/or chemical
      environment elements during reaction. The chemical maps obtained can also be used
      to identify preferred regions of gas reactions, e.g., grain boundaries or
      surfaces, etc. Various modifications of the microscope are described in detail,
      with suitable examples showing the performance.

PMID- 9779833
TI  - In situ transmission electron microscopy observations of the formation of self
      assembled Ge islands on Si.
AB  - The in situ transmission electron microscope allows us to visualise processes
      occurring at surfaces and interfaces in real time and is therefore capable of
      providing detailed, quantitative information about reaction mechanisms. We have
      used a UHV TEM equipped with in situ growth capabilities to study the process of
      chemical vapour deposition of Ge on Si(100), with particular emphasis on the
      formation of self-assembled, nanosize Ge islands. Video-rate image acquisition
      enables us to track the development of individual islands from nucleation onwards
      and to observe the introduction of dislocations as the strained islands relax.
      For islands less than 80 nm in diameter, which are coherently strained, we
      observe an interesting coarsening process during growth. This coarsening results
      in a bimodal distribution of island sizes at certain times and a narrow size
      distribution at later times. We explain the phenomenon by a model in which
      coarsening occurs among a population of islands for which the equilibrium island
      shape depends on the size. Numerical simulations of coarsening in the presence of
      a shape transition are in good agreement with experiment. As the islands grow
      larger, dislocations form and we observe rapid shape changes associated with
      dislocation introduction. These changes can also be understood by considering a
      strain-dependent island shape. The insight that these results provide into the
      understanding of island growth and evolution can be used to develop arrays of
      uniformly sized islands ("quantum dots") for a variety of potential applications.

PMID- 9779834
TI  - In situ growth and characterization of ultrahard thin films.
AB  - Results concerning the operation of a new ultrahigh vacuum (UHV) ion-beam
      assisted deposition system for in situ investigation of ultrahard thin films are
      reported. A molecular beam epitaxy (MBE) chamber attached to a surface science
      system (SPEAR) has been redesigned for deposition of cubic-boron nitride thin
      films. In situ thin film processing capability of the overall system is
      demonstrated in preliminary studies on deposition of boron nitride films on clean
      Si (001) substrates, combining thin film growth with electron microscopy and
      surface characterization, all in situ.

PMID- 9779835
TI  - Sintering and oxidation using a novel ultrahigh vacuum transmission electron
      microscope with in situ magnetron sputtering.
AB  - The synthesis and processing of materials is often highly sensitive to the
      presence of trace contaminants and a number of technologically important
      materials demand the clean conditions associated with an ultrahigh vacuum
      environment. With increasing interest in understanding materials phenomena
      occurring on smaller and smaller length scales, the transmission electron
      microscope is finding increasing application in the characterization of new
      materials and processes. The need for ex situ sample preparation prior to
      analysis can raise questions regarding the validity of the data, however, due to
      contamination and the introduction of microstructural artifacts. In this paper we
      discuss the application of the ultrahigh vacuum transmission electron microscope
      to in situ studies of materials synthesis. To illustrate the capabilities of the
      electron microscope in this context, we present two case studies: the synthesis
      and subsequent sintering of supported copper nanoparticles, and the initial
      stages of the growth of Cu2O on clean (001) Cu. We describe the novel aspects of
      the instrumentation used, the methods of sample preparation, and our application
      of the plan-view imaging technique to in situ investigations.

PMID- 9779836
TI  - Classification of childhood arthritis: divide and conquer.

PMID- 9779837
TI  - Evaluation of clinical agents on articular chondrocyte metabolism in vitro.

PMID- 9779838
TI  - Circulating levels of interleukin 10 and other cytokines in rheumatoid arthritis
      treated with cyclosporin A or combination therapy.
AB  - OBJECTIVE: To assess longitudinally over a 12 month period circulating serum
      levels of interleukin 10 (IL-10) and cytokines IL-3, IL-4, IL-6, and IL-12 in a
      cohort of patients with early onset rheumatoid arthritis (RA) treated with either
      cyclosporin A (CyA) or with combination therapy of CyA plus hydroxychloroquine as
      disease modifying antirheumatic drugs. METHODS: We studied 8 patients receiving
      CyA and 12 patients receiving CyA plus hydroxychloroquine. IL-3, IL-4, IL-6, IL
      10, and IL-12 were determined by ELISA at entry, after 2 weeks, after one month,
      after 6 months, and after 12 months. Rheumatoid factor levels and the possible
      appearance of monoclonal gammopathies over time were studied by immunofixation
      and immunoblotting techniques. RESULTS: The pooled data show that at entry only
      the median baseline levels of IL-10 (3.9 vs 1.6 pg/ml; p < 0.01) and IL-6 (16.9
      vs 1.4 pg/ml, p < 0.001) were higher in patients than in controls. IL-4 was not
      detectable. Some patients at entry (those with the longest disease duration) had
      detectable levels of IL-3. Only levels of IL-10 decreased significantly between
      entry and final values, in monotherapy and combination therapy as well. A single
      transient monoclonal band was observed after 6 months of treatment, which
      disappeared afterwards. No difference was seen in any of the cytokines between
      the CyA and the CyA plus hydroxychloroquine treated patients. CONCLUSION: During
      treatment with either CyA or CyA plus hydroxychloroquine, IL-10 levels decreased
      significantly. No additive effect of the 2 drugs was detected.

PMID- 9779839
TI  - Intention-to-treat analysis of 200 patients with rheumatoid arthritis 12 years
      after random allocation to either sulfasalazine or penicillamine.
AB  - OBJECTIVE: To assess existing disease modifying antirheumatic drugs (DMARD) using
      a strategy aiming for sustained suppression of inflammation. METHODS: We
      conducted intention-to-treat analysis of open randomized study [sulfasalazine
      (SASP) or penicillamine (PEN)], followup 12 years, conducted at specialist
      rheumatology clinics in Glasgow, Scotland. Subjects were 200 patients with
      rheumatoid arthritis (RA) with established disease. In this "true to life"
      approach, comorbidity was not an exclusion criterion unless it prejudiced
      assessment of drug toxicity. The main outcome measure was the Health Assessment
      Questionnaire (HAQ) functional score. RESULTS: Over 12 year followup 95 (47.5%)
      patients died; this was the commonest reason for study groups being unfulfilled.
      There was one drug related death (methotrexate). Patients who were socially
      disadvantaged were more likely to die prematurely. HAQ did not deteriorate
      significantly in those who continued taking their original DMARD, or in the SASP
      intention-to-treat group over 12 years. Sustained suppression of disease activity
      was possible in the entire group available for followup at 12 years. Most
      toxicity occurred early and no unexpected side effects were observed. CONCLUSION:
      High premature mortality in RA was confirmed and an association between mortality
      and deprivation was demonstrated. Sustained reduction in acute phase response was
      possible using sequential single DMARD. This study provides useful baseline and
      longterm information against which to evaluate combination therapy or new agents.

PMID- 9779840
TI  - Cysteine proteinase cathepsin K mRNA is expressed in synovium of patients with
      rheumatoid arthritis and is detected at sites of synovial bone destruction.
AB  - OBJECTIVE: Cysteine proteinases B and L have been shown to be involved in matrix
      degradation of joints in patients with rheumatoid arthritis (RA). Since the
      cysteine proteinase cathepsin K is assumed to play a pivotal role in osteoclast
      mediated bone resorption, we investigated the expression of cathepsin K in RA
      joints. METHODS: We studied 10 RA and 4 normal synovial specimens and 5 articular
      heads with RA lesions by in situ hybridization, applying specific riboprobes for
      cathepsin K, human collagen type I, and cathepsin B. Antibodies against
      monocyte/macrophage associated CD68 antigen were applied in immunohistochemistry.
      Reverse transcription-polymerase chain reaction (RT-PCR) and ribonuclease
      protection assay (RPA) were performed on 4 RA, 1 normal, and 1 immortalized
      normal fibroblast cultures. RESULTS: Cathepsin K mRNA expression was upregulated
      in RA synovium compared to normal synovium. Cathepsin K mRNA was expressed mainly
      by synovial fibroblasts. These data were confirmed by RT-PCR and RPA. In RA
      articular heads, cathepsin K mRNA was detected at sites where synovium attached
      and invaded underlying bone. The cells at these sites represented collagen type I
      and cathepsin B mRNA expressing fibroblasts as well as CD68+ macrophages and
      giant cells. In addition, a distinct expression of cathepsin K mRNA was also
      detected around lymphocytic infiltrates in RA synovium. CONCLUSION: The data
      indicate that cathepsin K is not only expressed by osteoclasts but also by
      synovial fibroblasts, and suggest that cathepsin K contributes to bone
      destruction mediated by RA synovial cells. The expression of cathepsin K around
      lymphocytic infiltrates suggests further to facilitate the movement of
      mononuclear cells through the perivascular interstitial matrix and thereby
      contribute to interstitial matrix turnover.

PMID- 9779841
TI  - Functional status predicts mortality in a community based rheumatoid arthritis
      population.
AB  - OBJECTIVE: To assess mortality, causes of death, and patient and disease
      characteristics predicting survival in a 5 year followup of a community based
      population of 103 patients with rheumatoid arthritis (RA) in the Kuusamo
      community in Northern Finland. METHODS: Mortality and causes of death were
      assessed on the basis of official data registers and death certificates. The
      relation of different baseline patient demographics and disease characteristics
      to mortality was evaluated. RESULTS: Functional status, measured by the lower
      extremity component of the Keitel function test, emerged as the most powerful
      factor predicting mortality. A poor lower extremity function (score > or = 13)
      increased the relative risk of death (hazard ratio 9.1) compared to well
      preserved lower extremity function. If the Keitel function test was omitted from
      the survival analysis, the best predictor of mortality was the Health Assessment
      Questionnaire. Twenty-one percent of the patients had died during the followup,
      the most usual cause of death being cardiovascular disease. CONCLUSION: Poor
      functional status, measured in this series by the Keitel function test, is a
      powerful predictor of mortality in RA. Our results confirm the importance of
      measurement of functional status in rheumatology care.

PMID- 9779842
TI  - Development, recurrence, and severity of infections in Mexican patients with
      rheumatoid arthritis. A nested case-control study.
AB  - OBJECTIVE: To determine factors associated with development, recurrence, and
      severity of infections in patients with rheumatoid arthritis (RA). METHODS: A
      hospital based nested case-control study in a referral center. The same evaluator
      reviewed clinical charts of 195 consecutive patients with RA seen in our clinic
      during 1993. Patients who had had at least one infection were classified as
      "cases" and the others as "controls." We examined 24 demographic, clinical,
      therapeutic, and infection related variables. A severity index was developed
      according to scores provided by 12 independent multidisciplinary evaluators.
      Recurrent infection was defined as > 2 different infections in the same patient
      during followup. Descriptive statistics were employed, with comparison between
      cases and controls by univariate analysis and multiple logistic regression.
      RESULTS: Two hundred eleven infections were detected in 1274 patient-years
      (incidence of 0.17 new infections per patient-year). We studied 174 women and 21
      men, mean 41 years of age, with a mean duration of symptoms of RA of 5 years.
      Ninety-five were cases and 100 controls. Cases had longer disease duration before
      admission and followup (p < 0.05). Infections most commonly seen were upper
      respiratory tract (n = 74), skin (41), urinary tract (27), and herpes zoster
      (15). Steroids and/or methotrexate (MTX) were associated in 95% of infections.
      Infection was associated with duration of RA before admission and followup,
      comorbidity, extraarticular disease, mean cumulative dose of MTX, time taking
      steroids, and mean daily dose of D-penicillamine, by univariate analysis.
      Severity of infection was related to the same variables and years of formal
      education, and recurrence of infection was related to time of followup and mean
      dose of MTX and steroids. Multiple logistic regression showed that variables
      associated with infection were cumulative MTX dose, time taking steroids, and
      mean daily dose of D-penicillamine. CONCLUSION: Infections were frequent in our
      RA population. The risk factors associated with infections were the cumulative
      dose of MTX, duration taking steroids, and mean daily dose of D-penicillamine.

PMID- 9779843
TI  - Employment patterns and their effect on health outcomes among women with
      rheumatoid arthritis followed for 7 years.
AB  - OBJECTIVE: To evaluate the effect of employment on health outcomes in a sample of
      women with rheumatoid arthritis (RA) and to test the hypothesis that employment
      confers a health benefit to women. METHODS: Seven hundred sixty women with a
      diagnosis of RA were recruited from a national random sample of private
      rheumatology practices in 1988, and 416 remained in the study after 7 years of
      followup in 1994. Women were interviewed each year by telephone to collect data
      on demographic variables, health status, and employment status. Clinical data
      were provided by referring physicians. RESULTS: Most women (175, 42%) were not
      employed outside the home 1988-94, although 96 of those women (23% of the sample)
      had been employed previously. Twenty-seven percent (n = 112) were employed all 7
      years and 31% (n = 129) had been employed between one and 6 years. Women who were
      employed had significantly better health outcomes measured by pain, disability,
      role functioning, and clinical status compared to those who were never employed
      and those who had been employed before the study. Women who were previously
      employed, but not employed during the study period experienced the worst health
      outcomes. This difference in health status, however, appeared before entry into
      this study. CONCLUSION: Employed women with RA had better health status than
      women who were not employed outside the home. Previously employed women had worse
      health outcomes than both working women and women who were never employed,
      suggesting that loss of employment is associated with worse health. Further
      research is needed to investigate underlying factors contributing to worse health
      status among unemployed women and to better health among employed women.

PMID- 9779844
TI  - Silica induced scleroderma--clinical and experimental aspects.
AB  - Clinical and experimental data concerning silica induced systemic sclerosis (SSc)
      are discussed in comparison to current knowledge of the pathophysiology of
      idiopathic SSc. About 280 patients with SSc after longterm silica dust exposure,
      some with associated silicosis, have been reported; 111 of them were analyzed as
      the largest cohort in our department. Based on clinical and laboratory data,
      silica induced and idiopathic SSc show similar pathophysiology and similar
      markers of the disease including vascular involvement, immunological
      abnormalities, and dysregulation of extracellular matrix metabolism. Experimental
      studies show that silica dust is able to activate microvascular endothelial
      cells, mononuclear cells from peripheral blood, and dermal fibroblasts in vitro
      in a fashion in common with pathophysiological events known from idiopathic SSc.

PMID- 9779845
TI  - Factors linked to disease activity in a French cohort of patients with
      spondyloarthropathy.
AB  - OBJECTIVE: To identify risk factors associated with disease activity, in a group
      of patients with spondyloarthropathy (SpA) living in France. METHODS: Patients
      fulfilling the ESSG or Amor criteria for SpA were enrolled in a cross sectional
      multicenter study. Disease activity was assessed using a French version of the
      Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Univariate and
      multivariate analyses were used to identify a link between BASDAI and disease
      characteristics, genetic factors, and environmental factors such as infectious
      events, mental stress, working conditions, and dietary factors. RESULTS: We
      studied 293 patients. On multivariate analysis, BASDAI appeared to be mainly
      linked to disease duration (negative correlation), the absence of sacroiliitis,
      and the "frequency of meals taken out of home" (negative correlation).
      CONCLUSION: Disease activity in a French population of patients with SpA appeared
      to be linked mainly to a shorter disease duration and a peripheral pattern of
      arthritis, as well as to dietary habits. The underlying links between this last
      environmental factor and disease activity remained hypothetical and could only
      reflect a nontested social factor.

PMID- 9779846
TI  - Enrichment of T cells carrying beta7 integrins in inflamed synovial tissue from
      patients with early spondyloarthropathy, compared to rheumatoid arthritis.
AB  - OBJECTIVE: To compare the expression of adhesion molecules on synovial T cells
      from patients with early spondyloarthropathy (SpA) and rheumatoid arthritis (RA),
      with special reference to the beta7 integrins alpha4beta7 and alphaEbeta7 in view
      of their intimate association with intestinal tissue. METHODS: Twenty-five
      synovial cell lines were generated by interleukin 2 (IL-2) expansion from
      synovial biopsies of patients with early SpA and RA, obtained from
      macroscopically inflamed synovial tissue by needle arthroscopy, and subsequently
      characterized by flow cytometry for CD3, CD4, CD8, L-selectin, CD11a, CD31, CD44,
      and alpha4beta7 and alphaEbeta7 integrin. RESULTS: In SpA, the beta7 integrin
      expression was increased, compared to RA. Furthermore, an inverse relation
      between alpha4beta7 and alphaEbeta7 was present in SpA (r = -0.75, p < 0.02), as
      on many mucosal T cells. In contrast, an opposite correlation was noted in RA (r
      = +0.84, p < 0.01), as similarly described on a subset of circulating T cells.
      CONCLUSION: Increased expression of beta7 integrins was noted on synovial T cell
      lines from SpA compared to RA, with discriminative correlations between
      alpha4beta7 and alphaEbeta7. This suggests a different origin of the synovial T
      cells in these diseases.

PMID- 9779847
TI  - Interferon-alpha treatment of Behcet's disease.
AB  - OBJECTIVE: To determine if interferon-alpha (IFN-alpha) is effective in Behcet's
      disease (BD). METHODS: Ten patients having active BD were entered into a 6 month
      open label trial of IFN-alpha therapy given by self-administered dose of 3
      million units subcutaneously daily. Provision was made for downward or upward
      dosing depending on predetermined responses. Four study centers followed the same
      protocol. Patients having ocular or neurologic inflammation at onset of the study
      were excluded. RESULTS: Seven patients completed the trial, while 3 were removed
      at 3 and 4 months for side effects or lack of efficacy. There was a substantial
      reduction in the number of oral and genital ulcers, cutaneous lesions, and
      articular signs and symptoms by the end of the study. Pain scores, global
      assessments, and prednisone dose also declined. The IFN-alpha dose at end of
      study averaged 1.5 million units. Significant side effects, besides the
      anticipated flu-like syndrome experienced by all the patients, included single
      instances of seizure, psychosis, psoriasis, and hyperthyroidism. CONCLUSION: The
      results suggest that IFN-alpha is effective therapy for some manifestations of
      Behcet's disease.

PMID- 9779848
TI  - Collagen induced arthritis in rats. Contrasting effect of subcutaneous versus
      intradermal inoculation of type II collagen.
AB  - OBJECTIVE: To determine the effect of subcutaneous (s.c.) as compared to
      intradermal (i.d.) inoculation of collagen type II (CII) in induction of collagen
      induced arthritis (CIA). METHODS: Dark Agouti (DA) and Lewis rats were injected
      with CII either i.d. or s.c.. A group of s.c. inoculated DA rats was re-injected
      with CII intradermally 45 days after first injection (s.c./i.d.). Arthritis was
      assessed by macroscopic scoring, histology, and immunohistochemistry. Levels of
      anti-CII antibody subtypes were measured by ELISA. RESULTS: Intradermal but not
      s.c. inoculation of CII resulted in histologically confirmed erosive arthritis in
      both Lewis and DA strains. Subcutaneous/intradermal inoculated DA rats developed
      mild CIA with lower arthritic scores and delayed onset. Lewis rats injected s.c.
      had lower levels of total Ig, IgG, IgG2a, and IgG2b and similar titers of IgG1
      compared to i.d. inoculated rats. In contrast, only IgG2b levels were lower in
      s.c./i.d. compared to i.d. rats. CONCLUSION: Our data suggest that s.c.
      administration of CII tolerises animals against autoimmune CIA.

PMID- 9779849
TI  - met-Enkephalin decreases in adjuvant arthritic ankles.
AB  - OBJECTIVE: To study whether met-enkephalin (met-enk) concentration changes in
      adjuvant arthritic ankles and spinal cords. METHODS: Adjuvant arthritis was
      induced by intradermal injection of Mycobacterium butyricum in paraffin oil, into
      the base of rat tail. The levels of met-enk were measured using radioimmunoassay
      and high performance liquid chromatography electrochemical detection in arthritic
      ankle and spinal cord of arthritic and control rats. Protein concentration was
      measured according to Lowry method. RESULTS: We observed a significant decrease
      of concentration of met-enk in ankle joints of chronic arthritic rats. However,
      increased concentration of met-enk was obtained in the spinal cord of chronic
      arthritic rats. CONCLUSION: The significant reduction of met-enk concentration in
      the arthritic ankle joints indicates a possible role for the endogenous opioid
      peptide in arthritis.

PMID- 9779850
TI  - The use of sulfasalazine in psoriatic arthritis: a clinic experience.
AB  - OBJECTIVE: To assess the tolerability of sulfasalazine in a clinic setting and
      determine its longterm effectiveness with respect to articular disease and
      prevention of radiographic progression in patients with psoriatic arthritis
      (PsA). METHODS: Patients who were given sulfasalazine during their attendance at
      the University of Toronto Psoriatic Arthritis Clinic were enrolled in the study.
      For patients that were able to tolerate sulfasalazine for at least 3 months a
      matched control was identified who did not receive sulfasalazine. The primary
      outcome measures were the tolerability of sulfasalazine, clinical response of the
      actively inflamed joints at 6 and 12 months, and the change in radiographic score
      at 24 months. RESULTS: Thirty-six patients received sulfasalazine. Fourteen of 16
      patients discontinued sulfasalazine due to one or more side effects occurring
      within 3 months of treatment initiation. For the remaining 20 patients, a 50%
      reduction in actively inflamed joint count was noted in 7/20 patients at 6 months
      and 11/15 patients at 12 months, compared to 7/19 patients in the control group
      at 6 months and 10/20 patients at 12 months. The mean change in the radiographic
      score at 24 months between the 2 groups was not statistically significant.
      CONCLUSION: Sulfasalazine was not well tolerated in patients with PsA in our
      clinic. For those able to tolerate sulfasalazine, there was no evidence of a
      treatment effect with respect to articular involvement. In addition,
      sulfasalazine does not appear to halt radiographic progression in PsA.

PMID- 9779851
TI  - In vitro suppression of transforming growth factor-beta induced stimulation of
      glycosaminoglycan synthesis by acetylsalicylic acid and its reversal by
      misoprostol.
AB  - OBJECTIVE: To determine if acetylsalicylic acid (ASA) suppresses the stimulatory
      effects of transforming growth factor-beta (TGF-beta) and insulin-like growth
      factor-1 (IGF-1) on glycosaminoglycan (GAG) synthesis by cultured bovine
      articular chondrocytes (BAC), and whether such a suppression can be counteracted
      by the addition of misoprostol, a prostaglandin (PG) E1 analog. METHODS:
      Confluent cultures of BAC were pre-incubated for 2 days with ASA (Aspirin) (250
      microg/ml), TGF-beta (10 ng/ml), IGF-1 (150 ng/ml), and misoprostol (80 ng/ml),
      separately and in different combinations, and for 2 more days with fresh medium
      and the same test agents in the presence of 35S-sulfate (10 microCi/ml). The
      radiolabelled GAG in the medium were then isolated, separated by cellulose
      acetate electrophoresis, and assayed for incorporated radioactivity, as a measure
      of GAG synthesis. RESULTS: TGF-beta, IGF-1, at their optimal concentrations, and
      misoprostol (80 ng/ml) stimulated GAG synthesis 2.6, 1.8, and 2.4-fold,
      respectively, of the control value, but ASA (250 microg/ml) showed no significant
      effect. ASA in combination with TGF-beta or misoprostol markedly suppressed the
      stimulation of GAG synthesis observed with either TGF-beta or misoprostol alone,
      but had no effect on the stimulation of GAG synthesis by IGF-1. Addition of
      misoprostol together with TGF-beta potentiated the stimulation of GAG synthesis
      by TGF-beta and abolished the suppressive effect of ASA on the stimulation of GAG
      synthesis by TGF-beta. Also, the magnitude of the stimulatory effect of
      misoprostol varied from batch to batch of misoprostol as well as for the same
      batch when it was added to the cultures either directly or after diluting with
      serum-free medium. CONCLUSION: In BAC cultures, ASA suppresses and misoprostol
      potentiates the stimulation of GAG synthesis by TGF-beta. Misoprostol also
      counteracts ASA induced suppression of the stimulation of GAG synthesis by TGF
      beta.

PMID- 9779852
TI  - Multifocal osteonecrosis.
AB  - OBJECTIVE: To study demographic, clinical, and radiographic staging patterns in
      patients with multifocal osteonecrosis to facilitate earlier diagnosis and
      optimize treatment. METHODS: Multifocal osteonecrosis was defined as disease of 3
      or more anatomic sites. Patients were characterized demographically, which
      included disease associations, corticosteroid and other agent usage, presenting
      joints, and symptomatology. Radiographically, patients were evaluated with plain
      radiographs and magnetic resonance imaging (MRI) scans of all joints to determine
      the presenting stage of the lesions. RESULTS: We found that 32 of 1056 (3%)
      osteonecrosis patients under our care had multifocal disease. Associated factors
      included systemic lupus erythematosus (13 patients), inflammatory bowel disease
      (5 patients), malignancy (4 patients), and renal transplantation (3 patients).
      Thirty of the 32 patients (94%) had a history of corticosteroid therapy, with the
      other 2 patients found to have a coagulopathy. All 32 patients had bilateral
      femoral head involvement and 30 of 32 had bilateral knee involvement, with the
      other 2 having only left knee lesions. Osteonecrosis was also seen in the
      shoulder (28 patients), ankle (8 patients), and 3 other sites. Overall, 201 sites
      were involved (6.3 per patient). The majority of joints presented in a pre
      collapse stage (77%). Patients most commonly presented with hip or multiple joint
      symptoms (22 patients, 69%). In 8 patients, the knee was the sole presenting
      symptomatic joint and the ankle and shoulder were the sole presenting symptomatic
      joints in one patient each. CONCLUSION: In patients with a diagnosis of
      osteonecrosis and complaints in other joints, these other areas should be fully
      evaluated with plain radiographs and, if inconclusive, with MRI. In patients with
      osteonecrosis not involving the femoral head, the patient's hips should be
      radiographically evaluated regardless of whether the patient is symptomatic.
      Patients diagnosed with osteonecrosis of the knee, shoulder, or ankle should have
      other joints evaluated, as such patients have multifocal disease roughly 50% of
      the time.

PMID- 9779853
TI  - Psychometric evaluation of a Korean Health Assessment Questionnaire for clinical
      research.
AB  - OBJECTIVE: The Health Assessment Questionnaire (HAQ) is a widely used, easily
      administered functional scale that has high reliability and validity. Although
      translated versions of HAQ are available, no Korean version exists. Our aim was
      to translate and confirm the reliability and validity of a Korean language
      version of the HAQ. METHODS: HAQ was translated into Korean by 3 translators and
      translated back into English by 3 different translators. Four questions were
      modified for the Korean culture. Fifty-six consecutive patients with RA were
      asked to rate the comprehensibility of the questions on a 4 point scale. The
      comprehensibility (responding with "3 or above") ranged from 76 to 98%. Another
      60 consecutive patients with RA were studied for the psychometric properties of
      the Korean version. RESULTS: The test-retest reliability of the Korean HAQ (KHAQ)
      yielded an intraclass correlation coefficient of 0.99. The Cronbach standardized
      alpha was 0.95 among 20 items. For construct validity, the correlation of KHAQ
      scores with disease severity [tender joint count, swollen joint count, patient's
      self-assessment of pain, erythrocyte sedimentation rate (ESR), Ritchie Index] was
      high and statistically significant, except for ESR. The 4 revised items were
      appropriate expressions of physical function since the correlations between each
      of the revised items and the first principal component are similar in magnitude
      to those between the 16 unchanged items and the principal component. CONCLUSION:
      The reliability and validity of the KHAQ is confirmed. The evaluation of
      responsiveness of the KHAQ is in progress.

PMID- 9779854
TI  - Utilization and predictive value of laboratory tests in patients referred to
      rheumatologists by primary care physicians.
AB  - OBJECTIVE: Antinuclear antibodies (ANA), rheumatoid factors (RF), and erythrocyte
      sedimentation rate (ESR) are among the most frequently requested tests in the
      diagnosis and investigation of connective tissue diseases (CTD). We evaluate the
      utilization patterns and predictive value of these tests in patients referred to
      rheumatologists by primary care physicians. METHODS: We reviewed the records of
      all new patients referred by primary care physicians in 1994 to 2 rheumatologists
      practicing at the University of Alberta. Data extracted from the records included
      diagnostic tests requested by referring primary care physicians, signs and
      symptoms at the initial rheumatology consult, and followup diagnoses. RESULTS:
      Seven hundred eleven new patients had been referred by over 300 primary care
      physicians: RF had been requested in 25%, ANA in 21%, and ESR in 29%. One hundred
      nine (15%) of the 711 patients had a CTD, 45 (6%) had rheumatoid arthritis (RA),
      and 8 (1%) systemic lupus erythematosus (SLE). The predictive values of positive
      tests for the diagnosis of CTD were low: 49% for RF, 29% for ANA, and 35% for
      ESR. For RA, the positive predictive values were 44% for RF, 8% for ANA, 17% for
      ESR; for SLE, 2, 12, and 3%, respectively. Diffuse musculoskeletal pain and
      fatigue were significantly associated with test utilization, although most
      patients with these symptoms had fibromyalgia or localized soft tissue
      rheumatism. CONCLUSION: Primary care physicians frequently requested
      autoantibodies in patients referred to rheumatologists. Most tests were negative,
      and were often requested in patients without CTD, resulting in low positive
      predictive values and questionable clinical utility. These findings suggest
      inappropriate overuse and lack of understanding of the use of autoantibody tests
      in diagnosing rheumatic diseases. A decrease in inappropriate use could be
      achieved by emphasizing that fatigue and diffuse musculoskeletal pain are not
      indicative of CTD in the absence of other features such as joint swelling,
      typical rash, or organ involvement.

PMID- 9779855
TI  - Effect of gamma-hydroxybutyrate on pain, fatigue, and the alpha sleep anomaly in
      patients with fibromyalgia. Preliminary report.
AB  - OBJECTIVE: To evaluate the effects of using a gamma-hydroxybutyrate (GHB)
      administered in divided doses at night in 11 patients previously diagnosed with
      fibromyalgia (FM). METHODS: Subjects completed daily diaries assessing their pain
      and fatigue levels and slept in the sleep laboratory before and one month after
      initiating GHB treatment. Polysomnographic recordings were evaluated for sleep
      stages, sleep efficiency and the presence of the alpha anomaly in non-REM sleep.
      RESULTS: There was a significant improvement in both fatigue and pain, with an
      increase in slow wave sleep and a decrease in the severity of the alpha anomaly.
      CONCLUSION: Further controlled studies are needed to characterize the clinical
      improvement and the polysomnographic changes we observed.

PMID- 9779856
TI  - Revision of the proposed classification criteria for juvenile idiopathic
      arthritis: Durban, 1997.

PMID- 9779857
TI  - Intravenous corticosteroids: adverse reactions are more variable than expected in
      children.
AB  - OBJECTIVE: To determine the frequency and severity of adverse reactions
      associated with high dose intermittent intravenous corticosteroids (IVCS) in
      children with rheumatic disease. METHODS: Prospective documentation of adverse
      reactions associated with IVCS given to 213 pediatric rheumatology patients over
      a 4 year period. RESULTS: Forty-six of the 213 children (22%) reported an adverse
      reaction. The 46 patients received 2622 doses of IVCS. Twenty-one patients (10%
      of all patients studied) had behavioral changes, including altered mood (14),
      hyperactivity (4), psychosis (2), disorientation (1), and sleep disturbances (3).
      Nonbehavioral adverse reactions included headache (5.2%), abdominal complaints
      (4.7%), pruritus (4.2%), vomiting (3.8%), hives (2.3%), hypertension (2.3%), bone
      pain (1.5%), dizziness (1.5%), fatigue (1%), lethargy (1%), hypotension (1%),
      tachycardia (1%), hyperglycemia (1%), fracture (1%), tremor (0.5%), anaphylaxis
      (0.5%), ulcer (0.5%), and "gray appearance" (0.5%). Using chi-squared analysis,
      there were no statistical differences in ethnicity (p = 0.54) or diagnosis (p =
      0.46) between patient groups, with or without adverse reactions. There was a
      significant statistical association between history of drug induced cutaneous
      reaction and adverse reactions to IVCS (p < 0.01). CONCLUSION: IVCS are
      associated with a spectrum of adverse reactions in children with rheumatic
      disease, of which volatile behavior is the most frequent. Children with a history
      of drug induced cutaneous reaction are more likely to have an adverse reaction to
      IVCS.

PMID- 9779858
TI  - Bone mineral density by single photon X-ray absorptiometry in Chilean children
      and adolescents.
AB  - OBJECTIVE: To assess bone mineralization in healthy Chilean children and
      adolescents, considering sex, age, height, and puberty. METHODS: In a descriptive
      cross sectional study, the appendicular bone mineral density (BMD) was measured
      by single photon x-ray absorptiometry at distal (D-BMD) and ultradistal (UD-BMD)
      regions of the forearm, in 571 healthy children and adolescents of Valparaiso and
      Vina del Mar, Chile, considering their age, sex, height, calcium intake, and
      pubertal development according to Tanner. RESULTS: Physical activity was regular;
      daily average calcium intake was 580 +/- 100 mg and the D-BMD and UD-BMD showed a
      3 step growth pattern: Slow increments between 4 and 8 years of age in girls (r =
      0.07 and r = 0.37, respectively) and between 4 and 12 years in boys (r = 0.17 and
      r = 0.39); sharp increases between 8 and 19 years in female adolescents (r = 0.78
      and r = 0.73) and between 12 and 20 years in male adolescents (r = 0.82 and r =
      0.67); and deceleration of growth from 19 years in female adolescents and 20
      years in males. Considering Tanner classifications (T), boys had significant
      differences in mean D-BMD between T3 and T4 (p < 0.001) and between T4 and T5 (p
      < 0.001) and in mean UD-BMD between T3 and T4 (p < 0.001). They achieve higher
      values than women in adulthood. Girls showed significant differences in mean D
      BMD between T3 and T4 (p = 0.003) and T4 and T5 (p < 0.001), and in mean UD-BMD
      between T3 and T4 (p = 0.016). Considering menarche, there was an important
      increment in bone mass up to 3 years after menarche, and it was significant until
      2 years after for D-BMD (p < 0.02) and 1 year after for UD-BMD (p < 0.001). In
      girls and boys, bone mass increments did not correlate with height increments. A
      delay in bone mass increments was observed at early Tanner stages. CONCLUSION:
      Between 4 and 8 years in girls and 4 and 12 years in boys, there is a slow
      increment in bone density correlated with age and sex. A steeper slope in bone
      growth started with puberty, correlated with Tanner stage. Bone mineral
      increments did not correlate with height increments. At the end of pubertal
      development bone acquisition slowed down. Men achieved higher bone density values
      than women.

PMID- 9779859
TI  - Prevalence of fibromyalgia in children: a clinical study of Mexican children.
AB  - OBJECTIVE: To determine the prevalence of fibromyalgia (FM) in schoolchildren
      according to the 2 stage classification process proposed by the 1990 American
      College of Rheumatology (ACR) Multicenter Criteria Committee on Fibromyalgia.
      METHODS: Stage 1: we administered a pain questionnaire to a sample of 548
      schoolchildren (264 boys, 284 girls; mean age 11.9 yrs, range 9-15). Stage 2: two
      rheumatologists examined all children with diffuse pain. Using thumb palpation,
      they examined 18 fibromyalgia tender points and 3 pairs of controls points
      followed by dolorimetry. Additionally, a random sample of 79 children with no
      pain were selected as controls, following the same procedures (thumb palpation
      and dolorimetry). The Wilcoxon test was used to compare the distribution of
      tenderness thresholds between FM and non-FM groups. Kappa statistics for multiple
      raters was used to assess interobserver agreement. RESULTS: Seven children, all
      girls, fulfilled the ACR diagnostic criteria for FM. Thus, the prevalence of FM
      in this group of schoolchildren reached only 1.2%. The girls with FM had a mean
      of 14 tender points, whereas controls (n = 79) had 2.4. Pain thresholds were 3.4
      kg in children with FM and 5.1 kg in controls (p = 0.004). CONCLUSION: The
      prevalence of FM in our study was 5-fold lower than a previous report. This
      variance may be due to (1) racial and sociocultural differences between
      populations; and (2) differences in methodological approach. The difficulties of
      making accurate estimates of FM across different studies are highlighted.

PMID- 9779860
TI  - Rupture of a hepatic artery aneurysm and renal infarction: 2 complications of
      fibromuscular dysplasia that mimic vasculitis.
AB  - Fibromuscular dysplasia (FMD) is one of the most important mimics of vasculitis.
      FMD is more prevalent in women and may cause infarcts of organ systems including
      the brain, intestines, and extremities. These acute clinical presentations often
      raise the suspicion of vasculitis and therefore rheumatologists will be asked to
      evaluate these patients. One of the frequent manifestations of FMD is renal
      artery involvement. Angiographic evaluation often shows a "string of beads"
      appearance of the renal arteries but sometimes only tapering of the vascular
      lumen or cutoffs may be seen. In contrast, hepatic artery involvement with FMD
      occurs much less frequently and may initially present with life threatening
      intraabdominal bleeding. Celiac angiograms of these patients often show
      aneurysms, a presentation similar to vasculitis. Only a high level of suspicion
      for FMD and careful evaluation of clinical facts will lead to correct diagnosis.
      This will prevent the wrong diagnosis of vasculitis and subsequent treatment with
      potentially toxic medications. We present 2 cases of FMD involving the renal and
      hepatic arteries that illustrate this diagnostic challenge.

PMID- 9779861
TI  - Association of aortic aneurysm in patients with systemic lupus erythematosus: a
      series of case reports and a review of the literature.
AB  - Systemic lupus erythematosus associated aortic aneurysm with or without
      dissection is an uncommon manifestation of the disease, but it exists and can be
      a grave complication. We describe 3 patients and compare them to others in the
      literature. Controlling hypertension and using steroid sparing agents where
      possible may help in preventing this complication.

PMID- 9779862
TI  - Polyarteritis with symptomatic intracerebral aneurysms at initial presentation.
AB  - Polyarteritis rarely involves the cerebral vasculature, and has not been reported
      to have an initial presentation with intracerebral aneurysms. We describe the
      first case of polyarteritis presenting with symptomatic intracerebral aneurysms.
      A literature review from 1966 to 1997 identified 5 additional cases with evidence
      of intracerebral aneurysms and polyarteritis. The cases reviewed all had evidence
      of longstanding systemic symptoms suggestive of polyarteritis prior to diagnosis.
      Polyarteritis with intracerebral aneurysms is associated with significant
      morbidity and mortality, and therefore must be recognized and treated early.

PMID- 9779863
TI  - A case of Stevens-Johnson syndrome associated with oxaprozin therapy.
AB  - We describe a case of Stevens-Johnson syndrome (SJS) associated with oxaprozin
      ("Daypro"), a relatively new nonsteroidal antiinflammatory drug (NSAID) of the
      propionic acid group. Our literature review shows that among the NSAID associated
      with SJS, oxicams have the highest risk. The risk is low for the propionic acid
      group. Indeed, the prevalence of their use was too low to permit an analysis of
      individual drugs. This is the first reported case of SJS associated with
      oxaprozin. Although the patient we describe survived the reaction, we think it is
      important to report such a potentially fatal reaction to a relatively newly
      available medication.

PMID- 9779864
TI  - Regression of carotid wall thickening after corticosteroid therapy in Takayasu's
      arteritis evaluated by B-mode ultrasonography: report of 2 cases.
AB  - We describe 2 young Japanese female patients with active Takayasu's arteritis
      whose diagnosis was mainly based on the characteristic ultrasonographic finding,
      that is, a circumferential vascular wall thickening in common carotid arteries.
      Following corticosteroid therapy, serial ultrasonographic examination documented
      the improvement of their thickened carotid walls (in Case 1 from 1.4 to 0.5 mm
      after 2 months of therapy, in Case 2 from 1.5 to 0.9 mm after 9 months of
      therapy). These cases emphasize that ultrasonography is useful for evaluation of
      the therapeutic effect as well as for the diagnosis of Takayasu's arteritis in
      its early stage.

PMID- 9779865
TI  - Descriptions of Reiter's disease in Mexican medical texts since 1578.

PMID- 9779866
TI  - Magnetic resonance imaging and focal myositis.

PMID- 9779867
TI  - Radiographic changes in the feet in patients with rheumatoid arthritis.

PMID- 9779868
TI  - Polymyalgia rheumatica. What's in a name?

PMID- 9779869
TI  - Severe hepatitis linked to B virus infection after withdrawal of low dose
      methotrexate therapy.

PMID- 9779870
TI  - Toxoplasma infection in patients with systemic lupus erythematosus.

PMID- 9779871
TI  - Polysynovitis associated with acute Epstein-Barr virus infection.

PMID- 9779872
TI  - Temporal arteritis after Hymenoptera sting.

PMID- 9779873
TI  - Amyopathic dermatomyositis complicated by interstitial pulmonary disease and
      pneumomediastinum.

PMID- 9779874
TI  - Groove sign in paraneoplastic palmar fasciitis.

PMID- 9779875
TI  - New advances in the treatment of hematologic malignancies: focus on topoisomerase
      I inhibitors. Introduction.

PMID- 9779876
TI  - An overview of topoisomerase I-targeting agents.
AB  - The camptothecins are a new class of antitumor agents that target topoisomerase
      I. Irinotecan and topotecan are the most widely used camptothecin analogs in
      clinical practice, with documented clinical activity in colorectal and ovarian
      cancer. Ongoing clinical trials with these agents are further characterizing
      their spectra of clinical activity and determining their optimal schedule of
      administration in combination with other anticancer agents. Newer camptothecin
      analogs in clinical development, such as 9-aminocamptothecin, 9
      nitrocamptothecin, GI1147211, and DX-8951f, are also being studied to determine
      if they have improved toxicity and efficacy profiles compared with existing
      analogs. The successful development of the camptothecins as antitumor agents
      demonstrates the importance of topoisomerase 1 as a target for cancer
      chemotherapy.

PMID- 9779877
TI  - The clinical pharmacology of topoisomerase I inhibitors.
AB  - The Chinese tree Camptotheca acuminata, or Xi Shu, brings us a unique class of
      chemotherapeutic agents known as the camptothecins. Because the parent compound
      exhibited excessive toxicity and poor aqueous solubility, synthetic and
      semisynthetic analogs were developed. These compounds contain a lactone ring that
      is necessary for activity and is easily hydrolyzed into the less active hydroxy
      carboxylic acid. Irinotecan, a semisynthetic analog is a prodrug that is cleaved
      by a carboxylesterase-converting enzyme to form the biologically active
      metabolite SN-38. The half-lives of irinotecan and SN-38 are relatively long, and
      both are commonly found in the lactone form. Topotecan differs from irinotecan in
      that it is found predominately in the inactive carboxylate form at neutral pH,
      but can be maintained in the lactone form at a lower pH. In phase I clinical
      trials, the antitumor activity of topotecan has been impressive. In vitro and in
      vivo studies have shown that combinations between topotecan and 5-fluorouracil or
      cisplatin have synergistic antitumor effects compared with topotecan alone. Two
      relatively new agents, 9-aminocamptothecin and GG211, have produced promising
      results against a variety of tumors.

PMID- 9779878
TI  - Induction of apoptosis by topotecan: implications for the treatment of leukemia.
AB  - Topotecan is a topoisomerase I inhibitor with activity against acute leukemia.
      Two phase I studies using infusional topotecan as a single agent demonstrated
      that the dose-limiting toxicity of topotecan in hematologic malignancies is
      mucositis; similar toxicity was observed in a phase I study of topotecan in
      combination with cytarabine. In the latter study, the percentage of bone marrow
      cells in S-phase correlated with response to therapy. Further studies of
      topotecan-based regimens in acute leukemia are indicated.

PMID- 9779879
TI  - Topotecan in the treatment of hematologic malignancies.
AB  - Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) are
      heterogeneous disorders for which there exist few active therapies and where the
      standard of care is still considered supportive. Identification of new effective
      therapies in MDS and CMML is a high priority for hematologic oncologists. We have
      evaluated the efficacy of single-agent topotecan, a topoisomerase I inhibitor, in
      patients with MDS (refractory anemia with excess blasts [RAEB] and refractory
      anemia with excess blasts in transformation [RAEB-T]) and CMML. Sixty patients
      (MDS = 30; CMML = 30) with a median age of 66 years were treated. Chromosomal
      abnormalities were present in half of the patients, as was thrombocytopenia.
      Topotecan was administered at 2 mg/m2 by continuous intravenous infusion over 24
      hours daily for 5 days every 4 to 6 weeks until remission, followed by one course
      every 4 to 8 weeks for a maximum of 10 courses. Nineteen patients (32%) achieved
      a complete response (CR); seven had hematologic improvement. CRs were observed in
      11 of 30 patients with MDS (37%) and eight of 30 patients with CMML (27%).
      Conversion to diploid karyotype was observed in eight patients with karyotypic
      abnormalities at diagnosis who later achieved a CR. History of prior chemotherapy
      and monocytosis was associated with poor prognosis. Mutation of the RAS oncogene
      was found in six CMML patients (20%), and none responded to topotecan therapy.
      The estimated 12-month survival rate was 33%, the median survival time was 9.3
      months, and the median remission duration was 7 months. The most significant
      toxicities were gastrointestinal, including mucositis (67%; severe 23%) and
      diarrhea (38%; severe 17%). Febrile episodes were noted in 85% of the patients,
      while documented infection occurred in 47%. Topotecan has demonstrated
      significant single-agent activity in MDS and CMML with generally manageable side
      effects. Future studies will evaluate topotecan-based combination therapies with
      topoisomerase II reactive agents, cytarabine, alkylating agents, and
      hypomethylating agents.

PMID- 9779880
TI  - The use of topoisomerase I inhibitors in multiple myeloma.
AB  - The standard treatment of multiple myeloma is systemic chemotherapy. Despite 30
      years of drug development in myeloma, there are no new drug regimens
      significantly superior to melphalan and prednisone. In addition, phase II studies
      of new drugs in myeloma have been disappointing, with low response rates and no
      prolongation in survival. The topoisomerase I (topo I) inhibitors are a new class
      of anticancer agents with a wide spectrum of activity in human malignancies.
      Recent evaluation of the topo I inhibitor topotecan demonstrated activity in
      advanced myeloma, suggesting a possible role for these drugs in the treatment of
      this disease. Further evaluation of the mechanisms of resistance to topo I
      inhibitors, study of combination therapy with topotecan, and evaluation of other
      topo I poisons in multiple myeloma is proposed.

PMID- 9779881
TI  - Qualitative models and fuzzy systems: an integrated approach for learning from
      data.
AB  - This paper presents a method for the identification of the dynamics of non-linear
      systems by learning from data. The key idea which underlies our approach consists
      of the integration of qualitative modeling techniques with fuzzy logic systems.
      The resulting hybrid method exploits the a priori structural knowledge on the
      system to initialize a fuzzy inference procedure which determines, from the
      available experimental data, a functional approximation of the system dynamics
      that can be used as a reasonable predictor of the patient's future state. The
      major advantage which results from such an integrated framework lies in a
      significant improvement of both efficiency and robustness of identification
      methods based on fuzzy models which learn an input output relation from data. As
      a benchmark of our method, we have considered the problem of identifying the
      response to the insulin therapy from insulin-dependent diabetic patients: the
      results obtained are presented and discussed in the paper.

PMID- 9779882
TI  - The Asgaard project: a task-specific framework for the application and critiquing
      of time-oriented clinical guidelines.
AB  - Clinical guidelines can be viewed as generic skeletal-plan schemata that
      represent clinical procedural knowledge and that are instantiated and refined
      dynamically by care providers over significant time periods. In the Asgaard
      project, we are investigating a set of tasks that support the application of
      clinical guidelines by a care provider other than the guideline's designer. We
      are focusing on the application of the guideline, recognition of care providers'
      intentions from their actions, and critique of care providers' actions given the
      guideline and the patient's medical record. We are developing methods that
      perform these tasks in multiple clinical domains, given an instance of a properly
      represented clinical guideline and an electronic medical patient record. In this
      paper, we point out the precise domain-specific knowledge required by each
      method, such as the explicit intentions of the guideline designer (represented as
      temporal patterns to be achieved or avoided). We present a machine-readable
      language, called Asbru, to represent and to annotate guidelines based on the task
      specific ontology. We also introduce an automated tool for the acquisition of
      clinical guidelines based on the same ontology, developed using the PROTEGE-II
      framework.

PMID- 9779883
TI  - Metareasoning and meta-level learning in a hybrid knowledge-based architecture.
AB  - Ahybrid knowledge-based architecture integrates different problem solvers for the
      same (sub)task through a control unit operating at a meta-level, the
      metareasoner, which coordinates the use of, and the communication between, the
      different problem solvers. A problem solver is defined to be an association
      between a knowledge intensive (sub)task, an inference mechanism and a knowledge
      domain view operated by the inference mechanism in order to perform the
      (sub)task. Important issues in a hybrid system are the metareasoning and learning
      aspects. Metareasoning encompasses the functions performed by the metareasoner,
      while learning reflects the ability of the system to evolve on the basis of its
      experiences in problem solving. Learning occurs at different levels, learning at
      the meta-level and learning at the level of the specific problem solvers. Meta
      level learning reflects the ability of the metareasoner to improve the overall
      performance of the hybrid system by improving the efficiency of meta-level tasks.
      Meta-level tasks include the initial planning of problem solving strategies and
      the dynamic adaptation of chosen strategies depending on new events occurring
      dynamically during problem solving. In this paper we concentrate on metareasoning
      and meta-level learning in the context of a hybrid architecture. The theoretical
      arguments presented in the paper are demonstrated in practice through a hybrid
      knowledge-based prototype system for the domain of breast cancer histopathology.

PMID- 9779884
TI  - Computerized brain atlases as decision support systems: a methodological
      approach.
AB  - This paper deals with the development of computerized brain atlases addressing
      both research and clinical needs. The authors analyze in detail the potential of
      these systems and discuss the capabilities and limitations of the digital atlases
      currently being developed around the world. The authors propose to reconsider the
      concept of a brain atlas, regarding both its content, and the way it has to be
      used and managed in order to set up more effective cooperation between the user
      and the system. Particular emphasis is placed on extensibility and reuse issues.
      which are critical in this rapidly evolving field. These orientations result from
      both the authors' experience and the analysis of current trends in the field of
      neuroimaging. The general methodology is illustrated with examples related to
      computer aided surgical planning.

PMID- 9779885
TI  - Acquiring background knowledge for machine learning using function decomposition:
      a case study in rheumatology.
AB  - Domain or background knowledge is often needed in order to solve difficult
      problems of learning medical diagnostic rules. Earlier experiments have
      demonstrated the utility of background knowledge when learning rules for early
      diagnosis of rheumatic diseases. A particular form of background knowledge
      comprising typical co-occurrences of several groups of attributes was provided by
      a medical expert. This paper explores the possibility of automating the process
      of acquiring background knowledge of this kind and studies the utility of such
      methods in the problem domain of rheumatic diseases. A method based on function
      decomposition is proposed that identifies typical co-occurrences for a given set
      of attributes. The method is evaluated by comparing the typical co-occurrences it
      identifies as well as their contribution to the performance of machine learning
      algorithms, to the ones provided by a medical expert.

PMID- 9779886
TI  - Supporting tools for guideline development and dissemination.
AB  - This paper describes a methodology for representing clinical practice guidelines
      and facilitating their introduction into the medical routine. Since this
      methodology can be exploited in a www environment, it can represent the basis for
      sharing clinical guidelines both between different institutions and between human
      and software agents cooperating within a clinical context. In addition, the
      proposed guideline formalization is intended to deal with patient and
      organization preferences. This goal is achieved by augmenting the guideline with
      decision analytic models and by linking the guideline with an organizational
      model of the clinical setting. The designed framework allows guideline
      development, tailoring and implementation, real-time access to the guideline
      prescriptions and guideline validation.

PMID- 9779887
TI  - Scenario recognition for temporal reasoning in medical domains.
AB  - The recognition of high level clinical scenes is fundamental in patient
      monitoring. In this paper, we propose a technique for recognizing a session, i.e.
      the clinical process evolution, by comparison against a predetermined set of
      scenarios, i.e. the possible behaviors for this process. We use temporal
      constraint networks to represent both scenario and session. Specific operations
      on networks are then applied to perform the recognition task. An index of
      temporal proximity is introduced to quantify the degree of matching between two
      temporal networks in order to select the best scenario fitting a session. We
      explore the application of our technique, implemented in the Deja Vu system, to
      the recognition of typical medical scenarios with both precise and imprecise
      temporal information.

PMID- 9779888
TI  - Disseminating medical knowledge: the PROforma approach.
AB  - Medical knowledge is traditionally disseminated via the publication of documents
      and through participation in clinical practice. Information technology offers to
      extend both modes of dissemination, via electronic publishing and virtual reality
      training, for example. AI promises even more radical changes through the
      possibility of publishing clinical expertise in the form of expert systems, which
      assist patient care through active decision support and workflow management.
      PROforma is a knowledge representation language that is designed to support this
      new mode of dissemination. It is based on an intuitive model of the processes of
      care and well-understood logical semantics. This paper provides a description of
      the language and associated software tools, and discusses its potential roles in,
      and implications for, medical knowledge publishing.

PMID- 9779889
TI  - A society of goal-oriented agents for the analysis of living cells.
AB  - This paper presents a new model for the segmentation and analysis of living
      cells. A multi-agent model has been developed for this application. It is based
      on a generic agent model, which is composed of different behaviors: perception,
      interaction and reproduction. The agent is further specialized to accomplish a
      specific goal. Different goals are defined from the different components of the
      cell images. The specialization specifies the parameters of the behaviors for the
      achievement of the agent's goal. From these goal-oriented agents, a society is
      defined, and it evolves dynamically as the agents are created and deleted. An
      internal manager is integrated in the agent to control the behavior's execution.
      It makes use of an event-driven scheme to manage the behavior priorities. The
      present design is mainly oriented toward image segmentation, however, it includes
      some features on tracking and motion analysis.

PMID- 9779890
TI  - Medical dictionaries for patient encoding systems: a methodology.
AB  - Medical language is highly compositional and makes extensive use of common roots,
      especially Latino-Greek roots. Besides words devoted to common sense, medical
      language presents some typical characteristics, especially on morphological and
      semantic aspects of word formation. Morphological decomposition and
      identification precedes semantic analysis. It is only when these two
      prerequisites are fulfilled that an attempt to grasp the meaning of a whole
      expression is made possible. The main aim of the proposed approach is that of
      coping with 'the lack of coverage of the medical lexical knowledge', in order to
      help physicians find the correct international classification for diseases (ICD)
      codes for a written diagnosis. The proposed methodology allows the development of
      a powerful dynamic dictionary dedicated to natural language processing in the
      field of diagnoses and narrative procedures. It describes the design of an
      analyser that can profit from a dictionary. The methods used have proved to be
      efficient for various classifications, s well as for multiple languages, as the
      system presently supports French, German, English and Dutch for ICD-9 and ICD-10
      classifications.

PMID- 9779892
TI  - A vision for managing care.

PMID- 9779891
TI  - Predicting survival in malignant skin melanoma using Bayesian networks
      automatically induced by genetic algorithms. An empirical comparison between
      different approaches.
AB  - In this work we introduce a methodology based on genetic algorithms for the
      automatic induction of Bayesian networks from a file containing cases and
      variables related to the problem. The structure is learned by applying three
      different methods: The Cooper and Herskovits metric for a general Bayesian
      network, the Markov blanket approach and the relaxed Markov blanket method. The
      methodologies are applied to the problem of predicting survival of people after
      1, 3 and 5 years of being diagnosed as having malignant skin melanoma. The
      accuracy of the obtained models, measured in terms of the percentage of well
      classified subjects, is compared to that obtained by the so-called Naive-Bayes.
      In the four approaches, the estimation of the model accuracy is obtained from the
      10-fold cross-validation method.

PMID- 9779893
TI  - HIV infection linked to substance use among hospitalized patients with severe
      mental illness.

PMID- 9779894
TI  - Obligation to the least well off in setting mental health service priorities: a
      consensus statement.

PMID- 9779895
TI  - Rural telepsychiatry is economically unsupportable: the Concorde crashes in a
      cornfield.

PMID- 9779896
TI  - A performance indicator spreadsheet for physicians in community mental health
      centers.

PMID- 9779897
TI  - The turn of the tide.

PMID- 9779898
TI  - Present at the creation: mental health law in eastern Europe and the former
      Soviet Union.

PMID- 9779899
TI  - Mental health staffing in managed care organizations: a case study.
AB  - This paper examines temporal changes in staffing ratios and configuration of
      mental health providers per 100,000 members within two full-service staff-model
      health maintenance organizations (HMOs). Overall workforce reductions in all
      classes of mental health professionals occurred in the two HMOs from 1992 to
      1995. Staffing ratios decreased in both HMOs for psychiatrists and psychologists.
      In one HMO, the ratio of clinical social workers also decreased over this period.
      Provider ratios from 1995 are benchmarked against state ratios per 100,000
      population. Workforce mix for the two HMOs is contrasted with a single-year
      average for a large managed behavioral health (carve-out) organization. The
      authors discuss potential implications of the findings for training of several
      categories of mental health professionals.

PMID- 9779900
TI  - The ethics of tailoring the patient's chart.
AB  - Because psychiatrists cannot include everything they observe and everything the
      patient says in the medical chart, they must select and tailor what goes into the
      chart. They should tailor the chart to focus on what is significant for the
      diagnosis and treatment of the patient. However, sometimes they tailor the chart
      for other purposes: to ensure that managed care will cover continued
      hospitalization, to protect themselves against malpractice claims, to secure a
      civil commitment, or to obtain a long-term placement for the patient. The authors
      of this paper present and analyze four cases in which psychiatrists tailor charts
      for these purposes. They discuss whether each psychiatrist's actions are
      ethically justified and consider whether tailoring the chart is a deceptive
      practice. In each case, they present reasons for and against this practice and
      suggest truthful alternatives designed to improve patient care, preserve social
      trust in the profession of psychiatry, and challenge serious failings in the
      health care system.

PMID- 9779901
TI  - Teaching psychiatric inpatients to re-enter the community: a brief method of
      improving the continuity of care.
AB  - OBJECTIVE: The study evaluated the effects of a brief manualized treatment
      program that taught patients skills to re-enter the community and actively follow
      through with their own care. METHODS: A total of 59 recently admitted inpatients
      with schizophrenia or schizoaffective disorder were randomly assigned to either
      the community re-entry program or an equally intensive regimen of occupational
      therapy. The community re-entry program consisted of eight 45-minute sessions
      conducted with groups of six to eight patients on a continuous, twice-a-day, four
      day-a-week schedule. The effects were measured by a review of the records of
      aftercare services that patients received in the month after discharge from the
      inpatient facility. Patients' knowledge and performance of the specific material
      taught in the community reentry program was ascertained through assessments
      conducted before and after training. RESULTS: Results indicated that patients in
      the community re-entry program significantly improved their knowledge and
      performance of the skills taught in the sessions, compared with patients in the
      occupational therapy group. Community re-entry participants were also
      significantly more likely to attend their first aftercare appointment than were
      occupational therapy participants (85 percent versus 37 percent). CONCLUSIONS:
      Not only can patients learn relatively complex material during a brief typical
      inpatient stay despite the acuteness of their illnesses, but they can also
      meaningfully improve the continuity of their own care by participating in a brief
      and highly structured training program. The program fits well within the time and
      staffing constraints of typical inpatient facilities.

PMID- 9779902
TI  - Decisions and justifications by community mental health providers about
      hypothetical ethical dilemmas.
AB  - OBJECTIVE: Community-based treatment of persons with serious mental illness
      requires providers to become involved in clients' personal lives to a greater
      degree than does hospital-based treatment. The study examined attendant ethical
      dilemmas, especially for staff who lack professional training or work in rural
      communities. METHODS: A total of 95 staff members from five community mental
      health centers read 14 vignettes describing ambiguous ethical dilemmas involving
      professional role boundaries or client confidentiality. Twenty-seven staff
      members were from rural agencies, and 68 from urban-suburban agencies; 60 were
      direct care staff, and 35 were supervisory. Participants were asked to make and
      justify a more conservative or a less conservative decision in response to each
      dilemma. RESULTS: Years of experience as a mental health provider and previous
      ethics training correlated positively with staff having experienced more
      situations similar to those in the vignettes; however, these variables were not
      related to the decision made or the type of ethical justification for it. When
      the analysis controlled for experience and previous ethics training, staff made
      fewer conservative decisions in boundary dilemmas than in confidentiality
      dilemmas. Compared with nonrural providers, rural providers had experienced more
      boundary dilemmas and made fewer conservative decisions in response to them.
      CONCLUSIONS: Boundary problems occur frequently in community-based services,
      especially in rural settings, and may or may not be handled conservatively. With
      the expansion of case management and other in vivo services, better understanding
      of ethical risks and informal practices will help improve services and provide
      appropriate training and supervision of staff.

PMID- 9779903
TI  - Program directors' views of the effect of managed care on substance abuse
      programs in Los Angeles county.
AB  - OBJECTIVE: This study sought information about the effect of managed care on
      substance abuse treatment programs through a survey of program directors.
      METHODS: Fifty program directors who supervised a total of 134 substance abuse
      treatment programs in Los Angeles County completed a survey during the period
      from January to May 1997 on program changes made in response to managed care,
      major concerns, the advantages and disadvantages of managed care, and plans for
      further program changes to succeed in the managed care environment. RESULTS:
      Program directors reported that the most frequent change made in response to
      managed care was increased outreach and marketing. Their greatest concern in the
      managed care environment was being forced to provide the least costly service,
      rather than the best care for patients. Respondents identified an increased focus
      on outcomes as an advantage of managed care and restrictions on services due to
      contractual agreements as a disadvantage. Planned program changes addressed the
      areas of program structure, types of programs offered, staff composition, revenue
      generation, referral sources, prevention, outcome measures, relationships with
      other organizations, and accreditation and certification. CONCLUSIONS: Although
      some substance abuse treatment programs seem to be reducing their scope or
      preparing to close in response to managed care, others are developing strategies
      to survive and even thrive in this new economic environment.

PMID- 9779904
TI  - Case management and recidivism of mentally ill persons released from jail.
AB  - OBJECTIVE: The study tested the hypothesis that case management provided to
      mentally ill offenders both in jail and after release from jail would reduce
      their recidivism. METHODS: A total of 261 inmates of the Lucas County (Toledo,
      Ohio) jail who were diagnosed with a mental disorder were tracked for three years
      after their release. The relationships between recidivism and diagnostic,
      demographic, and case management variables were examined through event history
      analysis. RESULTS: Recidivism was associated with age, employment, previous
      arrests, and receipt of community-based case management. Receipt of jail-based
      case management, although not directly related to recidivism, significantly
      increased the probability of receiving community-based case management. Receipt
      of community case management was significantly associated with a lower
      probability of rearrest and a longer period before rearrest. CONCLUSIONS: This
      study found hopeful signs that expanding access to case management, both inside
      and outside jail, will help mentally ill people live in their communities and
      stay out of jail.

PMID- 9779905
TI  - Gold Award: Integrating dialectical behavioral therapy into a community mental
      health program. Mental Health Center of Greater Manchester, New Hampshire.

PMID- 9779906
TI  - Gold Award: Confronting mood disorders through clinical care, research, and
      education. McMaster Regional Mood Disorders Program, Hamilton Psychiatric
      Hospital, Hamilton, Ontario.

PMID- 9779907
TI  - Significant Achievement Awards: Creating a continuum of care for a previously
      unserved population--McHenry County (Ill.) Traumatic Brain Injury Case Management
      Program.

PMID- 9779908
TI  - Significant Achievement Awards: A summer camp for children and adolescents with
      severe emotional and behavioral problems--Project Discovery, Moundbuilders
      Guidance Center, Inc., Newark, Ohio.

PMID- 9779909
TI  - Using recidivism rates as a quality indicator for substance abuse treatment
      programs.
AB  - Recidivism is a widely used quality indicator for inpatient substance abuse care.
      However, unadjusted recidivism rates do not account for important confounding
      variables, which may lessen their usefulness as a quality indicator. Using a
      study of a statewide network of inpatient substance abuse services in
      Connecticut, the authors present a method for sampling existing administrative
      data and adjusting recidivism rates. The method can be used by managers of
      provider networks to assess whether patient subgroups with different demographic
      or geographic characteristics have equal access to care; to check for potential
      weaknesses in services, facilities, or systems; and to identify programs with
      unusually high or low recidivism rates for improvement or replication.

PMID- 9779910
TI  - Factors affecting engagement of dual diagnosis patients in outpatient treatment.
AB  - This study examined factors associated with engagement in outpatient treatment of
      patients with dual diagnoses of psychiatric disorder and substance use disorder.
      The charts of all 57 patients referred to a dual diagnosis treatment program
      during a six-month period were reviewed, and data on patients' substance use
      diagnosis, psychiatric diagnosis, sex, ethnicity, and referral source were
      collected. Patients referred from inpatient treatment were more likely to attend
      three or more appointments at the dual diagnosis program than those referred from
      outpatient treatment. Substance of abuse interacted with both referral source and
      sex in predicting engagement.

PMID- 9779911
TI  - Factors associated with suicide attempts among patients with schizophrenia.
AB  - This study explored the association between psychosocial variables and symptoms
      among patients with schizophrenia-spectrum disorders who have attempted suicide
      and those who have not attempted suicide. Of 336 patients with a DSM-III-R
      diagnosis of schizophrenia or schizoaffective disorder who were consecutively
      evaluated at a university-affiliated clinical research center, 98, or 29.2
      percent, reported one or more suicide attempts. Compared with patients who had
      not attempted suicide, patients who had made an attempt had a greater number of
      lifetime depressive episodes, an earlier age of onset of their illness, and an
      earlier age at first hospitalization.

PMID- 9779912
TI  - Substitution of immediate-release valproic acid for divalproex sodium for adult
      psychiatric inpatients.
AB  - In a prospective open-label study, the substitution of immediate-release valproic
      acid for divalproex sodium was evaluated in the treatment of 47 adult psychiatric
      inpatients who had been stabilized on divalproex for at least one month. After
      two weeks, no significant change in Clinical Global Impressions scale (CGI)
      scores or in seizure frequency occurred, and serum valproate concentrations
      decreased by 14.4 percent (p=.001). One patient was restarted on divalproex
      because of gastrointestinal complaints. Among the 19 patients remaining
      hospitalized at six months, mean CGI scores did not significantly change. Costs
      were reduced 83 percent; annual savings per patient was approximately $905. These
      preliminary results suggest that many chronic psychiatric inpatients stabilized
      on divalproex may be safely switched to valproic acid.

PMID- 9779913
TI  - Hyperammonemia and coma developed by a woman treated with valproic acid for
      affective disorder.
AB  - The authors report the case of a patient who developed hyperammonemia and coma
      during therapy with valproic acid for affective disorder. Onset of the coma was
      gradual and initially interpreted as a therapeutic reduction in the patient's
      anxiety. In a psychiatric setting, treatment of hyperammonemia may be delayed if
      a patient's increasing lethargy is interpreted as a therapeutic response. Staff
      may need to be educated about the potential for hyperammonemia, and patients
      whose tolerance for valproic acid is unknown may need to be monitored for liver
      function and blood levels of urea and ammonia.

PMID- 9779914
TI  - Family advocacy.

PMID- 9779915
TI  - Family advocacy.

PMID- 9779916
TI  - Family advocacy.

PMID- 9779917
TI  - Employment and disability.

PMID- 9779919
TI  - 1997 National Survey on Drug Abuse finds increase in illicit drug use, primarily
      marijuana, among U.S. youth.

PMID- 9779918
TI  - Depot antipsychotic drugs revisited.

PMID- 9779920
TI  - APA task force report urges strong opposition to laws committing sexual predators
      to mental health facilities. American Psychiatric Association.

PMID- 9779921
TI  - Feeding-induced changes in temporal patterning of muscle activity in the lobster
      stomatogastric system.
AB  - In the lobster Homarus gammarus, rhythmic masticatory movements of the foregut
      gastric mill are generated by a small neural network in the stomatogastric
      ganglion. We have used EMG recordings from intact animals to analyse gastric
      network output in relation to cycle period before and after feeding. In pre
      prandial conditions, muscles controlling lateral teeth closure and medial tooth
      protraction (driven by MG and GM motor neurons, respectively) express relatively
      constant, return stroke-like burst durations, but change to a variable-duration
      power stroke-like phenotype after feeding. In contrast, the LPG neuron-innervated
      lateral teeth opener muscle switches from power stroke to return stroke-like
      behavior. Thus alternate phases within a single motor program may invert their
      temporal properties according to the behavioral situation.

PMID- 9779923
TI  - Synaptic density in the arcuate nucleus of female rats approaching middle age.
AB  - Synaptic number and synapses/neuronal cell membrane were evaluated from
      ultrastructural micrographs of the arcuate nucleus from 90-, 120-, 180-, and 240
      day female rats grouped into ovary-intact or ovariectomized animals treated with
      peanut oil vehicle or estradiol benzoate (10 microg/100 g body weight) for 3
      days. In ovary-intact rats, synaptic density was significantly less in middle
      aged 240 day animals than in 90-, 120-, or 180-day animals with greatest decrease
      occurring between 180- and 240-day animals. Ovary-intact and ovariectomized
      animals treated with estradiol benzoate had significantly higher sera estradiol
      levels, but the estradiol was ineffective in increasing synaptic density in the
      middle aged animals. Logistical regression confirmed a correlation between a
      decrease in synapses and increasing age but not estradiol treatment.

PMID- 9779922
TI  - An early stage mechanism of the age-associated mitochondrial dysfunction in the
      brain of SAMP8 mice; an age-associated neurodegeneration animal model.
AB  - In order to characterize the early stage of mitochondrial dysfunction, we
      investigated the redox state and oxidative phosphorylation of the brain
      mitochondria from 2-month-old Senescence-accelerated mouse (SAM)P8 and SAMR1
      mice; SAMP8 mice exhibit various signs of age-associated neurodegeneration and
      rapid mitochondrial dysfunction, although SAMR1 mice do not. The redox state was
      estimated as the reduction rate of Cu-pyruvaldehyde-bis (N4
      methylthiosemicarbazone) (Cu-PTSM), the reduction of which is closely related to
      the electron leakage from the mitochondrial electron transport system in the
      brain, using electron spin resonance spectrometry (ESRS). The oxidative
      phosphorylation was measured polarographically. The SAMP8 mouse brain
      mitochondria demonstrated higher redox state and a higher activity of
      mitochondrial respiration with lower respiration control ratio than the
      mitochondria of SAMR1 mouse brains. This indicates that an inefficient
      hyperactive state can exist in the mitochondrial electron transport system before
      the age-associated mitochondrial dysfunction develops.

PMID- 9779924
TI  - Immunolocalization of transcription factor NF-kappaB in inclusion-body myositis
      muscle and at normal human neuromuscular junctions.
AB  - To investigate whether nuclear factor kappaB (NF-kappaB) is involved in the
      pathogenesis of inclusion-body myositis (IBM), we immunostained muscle biopsies
      of eight patients with IBM with specific antibodies against its p50 and p65
      subunits. Approximately 70% of IBM vacuolated muscle fibers had strong focal
      accumulations of both NF-kappaB p50 and p65, which by immunoelectronmicroscopy,
      localized mainly to clusters of paired-helical filaments (PHFs). Virtually all
      necrotic fibers, in various muscle biopsies, had diffusely strong p50
      immunoreactivity, whereas p65 immunoreactivity was present only in a small subset
      of necrotic fibers. At all neuromuscular junctions, postsynaptically there was
      strong p65 but no p50 immunoreactivity. Our data suggest that NF-kappaB plays a
      role in IBM pathogenesis. Different distributions of NF-kappaB subunits in
      necrotic fibers and at normal neuromuscular junctions (NMJs) suggests different
      roles of each subunit in human muscle pathology and physiology.

PMID- 9779925
TI  - Function of GABA rho1 receptors is up-regulated by chronic GABA treatment in
      Xenopus oocytes.
AB  - This study was aimed to investigate the effect of chronic gamma-aminobutyric acid
      (GABA) treatment on homomeric GABA rho1 receptors expressed in Xenopus oocytes.
      The rho1 mRNA-injected oocytes were incubated with 10 mM GABA for 2, 6, 24, 48 or
      72 h, prior to the assessment of GABA-gated ion currents. The results showed that
      GABA exposure for more than 6 h dramatically enhanced the peak GABA-activated
      currents. In addition to current amplitude, the apparent GABA potency and
      cooperativity were significantly increased. The enhancement reached its plateau
      after a 24-h exposure. The up-regulation of GABA current amplitude was completely
      inhibited by cycloheximide, a translation inhibitor. This suggests that chronic
      GABA treatment may increase the translational activity of GABA rho1 subunit in
      Xenopus oocytes.

PMID- 9779926
TI  - Longitudinal changes in quantitative EEG during long-term tacrine treatment of
      patients with Alzheimer's disease.
AB  - Quantitative EEG is a potentially useful tool in demonstrating the effects of
      treatments with acetylcholinesterase (AChE) inhibitors on the progression of
      Alzheimer's disease (AD). In order to define the profile of EEG changes during
      tacrine long-term treatment, for 12 months we followed 15 AD patients receiving
      an optimal individually tolerable dose. After 3 months theta global field power
      (GFP) was significantly reduced, and after 6 months both theta and delta GFP
      decreased. Theta GFP was still reduced after 12 months of treatment when compared
      to the baseline. Significant decreases in fast activities of beta 1 and beta 2
      GFP were also observed. The untreated reference group (n = 10) did not show any
      significant changes in GFP after 12 months follow-up, although generators of
      theta activity had a significant shift towards posterior regions. These findings
      suggest that slowing in fast EEG frequencies during chronic treatment with AChE
      inhibitors may provide an early indicator of declining treatment efficiency.

PMID- 9779927
TI  - Neuroprotection against oxidative stress by serum from heat acclimated rats.
AB  - Exposure of PC12 cells, to 1% serum derived from normothermic (CON) rats resulted
      in 79% cell death. Sister cultures treated with 1% serum derived from heat
      acclimated (ACC) rats, were neuroprotected and expressed a significant reduction
      in cell death. In PC12 cells exposed to a free radical generator causing an
      oxidative stress, 90% cell death was measured in CON serum treated cultures,
      while ACC serum treated cultures were neuroprotected. Xanthine oxidase activity
      and uric acid (UA) levels were lower in ACC serum compared to CON. Addition of UA
      to both sera abolished the difference in cell viability, and toxicity of ACC
      serum reached that of CON. These findings suggest a causal relationship between
      the lower levels of UA in ACC and the neuroprotective effect observed. The
      present study proposes heat acclimation as an experimental and/or clinical tool
      for the achievement of neuroprotection.

PMID- 9779928
TI  - Shift of the beating field of vestibular nystagmus: an orientation strategy?
AB  - We investigated in humans whether the shift of the beating field, which is often
      observed during vestibular nystagmus, could be related to some strategy of
      orientation. Eye movements were measured with an infrared system during an
      experiment on self-motion perception in the dark. Subjects were asked to rotate,
      by means of a joystick, a mobile robot on which they were seated in order to
      reproduce a previously imposed passive rotation. We suggest that the shift of the
      ocular beating field is the manifestation of two different orientation strategies
      based on allocentric and egocentric reference frames, respectively. It is also
      proposed that subjects who preferably used the first strategy exhibited large
      shifts of the beating field, while the others who probably used egocentric memory
      did not exhibit any shift.

PMID- 9779929
TI  - Induction of matrix metalloproteinase-2 in human immunodeficiency virus-1
      glycoprotein 120 transgenic mouse brains.
AB  - Human immunodeficiency virus (HIV)-1 can invade the brain and cause degeneration
      of the central nervous system, resulting in a host of cognitive and motor
      impairments. HIV-1 glycoprotein 120 (gp120), has been implicated in the
      neurodegenerative effects of HIV infection. Here, gp120's neurotoxic potential is
      demonstrated in both transgenic mice and cultured cells. We observed that gp120
      causes an induction of matrix metalloproteinase (MMP)-2 activity and protein in
      transgenic mouse brains and in transfected C6 cells. We propose that induced MMP
      2 may contribute to a neurodegenerative environment by degrading extracellular
      matrix (ECM) fibronectin and type IV collagen.

PMID- 9779930
TI  - Postischemic hypothermia induced by eugenol protects hippocampal neurons from
      global ischemia in gerbils.
AB  - We studied whether eugenol provides neuroprotection against delayed neuronal
      death in the hippocampal CA1 region following a 5 min occlusion of the common
      carotid arteries bilaterally under either free-regulating temperature (TF) or
      maintained temperature (TM, 37 degrees C) conditions in gerbils. Right after
      occlusion of the carotid arteries, we injected eugenol intraperitoneally at
      concentrations of either 50, 100, or 200 mg/kg. There was significant
      preservation of neuronal cells in the CA1 region in the eugenol-treated groups 7
      days after the ischemic insult in the TF condition, with respective survival
      values of 26, 43, and 68%. In the TM condition, however, significant
      neuroprotection was only seen with eugenol concentrations of 100 and 200 mg/kg
      (32% and 52%, respectively). When the rectal temperature was maintained at 38
      degrees C for 30 min after occlusion of the carotid arteries, no reduction in CA1
      damage was observed with any dose of eugenol. These results suggest that eugenol
      may provide neuroprotection against ischemic damage by its hypothermic action.

PMID- 9779931
TI  - Non-noxious stimulation of the glenohumeral joint capsule elicits strong
      inhibition of active shoulder muscles in conscious human subjects.
AB  - Information about the function of joint afferents in humans is scarce. Therefore,
      we investigated the influence of non-noxious electrical stimulation of the
      glenohumeral joint capsule on the activity of shoulder muscles in conscious human
      subjects. Stimulation electrodes were inserted in the joint capsule during
      arthroscopy. Only when the anterior inferior part of the capsule including the
      glenohumeral ligament was stimulated a strong and rather long latent general
      inhibition in voluntarily activated shoulder muscles was observed (average
      latency and duration: 33 ms and 76 ms, respectively). The inhibition was followed
      by an excitation and a few but inconsistent oscillations in the muscle activity.
      The results suggests a potent proprioceptive feedback pathway for the motor
      control of the human shoulder joint. However, further investigations are needed
      to clarify the involvement of several possible afferent pathways.

PMID- 9779932
TI  - Increased mitochondrial DNA deletion in the brain of SAMP8, a mouse model for
      spontaneous oxidative stress brain.
AB  - Oxidative stress is considered to be closely correlated with degenerative brain
      abnormalities. In this study, the plausibility of a SAMP8 strain mouse showing
      memory deterioration and short life span as an oxidative stress brain model was
      evaluated. Mitochondrial DNA deletions were detected using polymerase chain
      reaction (PCR) as cumulative spontaneous oxidative stress. In the 4-8-week-old
      SAMP8 brain, multiple mitochondrial DNA (mtDNA) deletions were already found and
      the contents were significantly higher than those of SAMR1 or ddY controls.
      Enzyme activity studies indicated that electron transport was disturbed at the
      lower site of the chain and the electronegativity of the upper site might be
      increased, a cause of radical production and therefore oxidative stress.

PMID- 9779933
TI  - Co-localization of 5-HT1B- and 5-HT1D receptor mRNA in serotonergic cell bodies
      in guinea pig dorsal raphe nucleus: a double labeling in situ hybridization
      histochemistry study.
AB  - In order to provide further details on the cellular localization of 5-HT1B- and 5
      HT1D receptor mRNA in the dorsal raphe nucleus, we performed, in the same
      sections of guinea-pig dorsal raphe nucleus, double labeling in situ
      hybridization histochemistry for: (1) 5-HT1B receptor mRNA and 5-HT1D receptor
      mRNA, (2) 5-HT1B receptor mRNA and 5-HT transporter (5-HTT) mRNA as marker for
      serotonergic neurons and (3) 5-HT1D receptor mRNA and 5-HTT mRNA. The 5-HT1B
      receptor mRNA was present in all cells containing 5-HT1D receptor mRNA.
      Similarly, both 5-HT1B- and 5-HT1D receptor mRNA was present in all 5-HTT mRNA
      positive cells. The present study demonstrates that 5-HT1B- and 5-HT1D receptor
      mRNA is co-localized in serotonergic cell bodies of the guinea pig dorsal raphe
      nucleus.

PMID- 9779935
TI  - Effects of the selective metabotropic glutamate agonist LY354740 in a rat model
      of permanent ischaemia.
AB  - The neuroprotective effects of a systemically active, potent, group II selective
      metabotropic glutamate receptor agonist, LY354740, was assessed in the middle
      cerebral artery occlusion model of focal ischaemia in rats. LY354740 (0.3, 3.0 or
      30.0 mg/kg) was administered subcutaneously (s.c.) 30 min prior to and 3 hours
      after the induction of ischaemia. Twenty four hours after the ischaemic insult,
      the brains were processed for the evaluation of infarct volumes. No significant
      reduction in infarct volumes were observed in treated animals at any of the doses
      investigated. These data provide no support for the view that group II
      metabotropic glutamate receptors have a major influence on ischaemic damage in
      this model.

PMID- 9779934
TI  - Induction of hypoxia inducible factor 1 by oxygen glucose deprivation is
      attenuated by hypoxic preconditioning in rat cultured neurons.
AB  - Hypoxia-inducible factor 1 (HIF-1) is a posttranscriptionally regulated
      transcription factor, controlling several hypoxia-inducible genes. Here we show a
      rapid and transient increase of HIF-1 DNA binding activity in a dose dependent
      manner in primary cortical neurons of rats exposed to oxygen glucose deprivation
      (OGD) for 30, 60, 90, or 120 min. A reduced induction of binding activity was
      observed when neurons were preconditioned by a non-lethal OGD interval (60 min)
      48 h prior to the 90 min OGD. Thus, hypoxic preconditioning reduces activation of
      HIF-1 binding activity. The molecular mechanism of HIF-1 activation, its target
      genes, and its role in tolerance induction and/or ischemia induced damage remain
      to be elucidated.

PMID- 9779936
TI  - Dense innervation of Deiters' and Hensen's cells persists after chronic
      deefferentation of guinea pig cochleas.
AB  - Innervation of Deiters' and Hensen's cells has been described in the organ of
      Corti of several mammalian species and has been suggested to arise from the
      olivocochlear (OC) efferent system (Wright and Preston [1976] Acta Otolaryngol.
      82:41-47). In the present study, antineurofilament immunostaining was used to
      reveal these outer supporting cell fibers (OSCFs) in the normal guinea pig. In
      control ears, OSCFs were absent in the basal half of the cochlea but increased in
      number steadily toward the apex, peaking at values of over 1,200 fibers/mm. These
      values indicate a far more profuse innervation of supporting cells than has been
      described previously, suggesting that most OSCFs were not stained in previous
      immunohistochemical studies. Chronic cochlear deefferentation was used to test
      whether OSCFs are part of the OC system. The OC bundle was transected
      unilaterally, and the animals were allowed to survive for 4-8 weeks. Completeness
      of deefferentation was assessed by using acetylcholinesterase staining of the
      brainstem and measurement of the density of OC fascicles in the cochlea. By using
      these metrics, unilateral deefferentation was nearly complete in three animals.
      In successfully deefferented cases, the OSCF innervation density was not
      statistically different from control values. We conclude that the vast majority
      of OSCFs are not of OC origin. We speculate that they may be branches of type II
      afferent fibers to outer hair cells and that a smaller population of OSCFs with
      different morphology and immunoreactivity may arise from the OC system.

PMID- 9779937
TI  - Evidence for the presence of the tissue-specific transcription factor Pit-1 in
      lancelet larvae.
AB  - Recent molecular studies have noted the affinity among cephalochordates and
      vertebrates. In particular, a cluster of vertebrate-like homeobox genes regulates
      the development of the lancelet Branchiostoma lanceolatum. A previous study has
      outlined the expression pattern of the pituitary-specific transcription factor
      Pit-1 in adult lancelets. Pit-1 belongs to the POU family of transcription
      factors, which, like homeotic proteins, are members of the helix-turn-helix
      superfamily of proteins. POU is an acronym for Pit-1, Oct-1 and Oct-2, and Unc
      86. In the present work, we investigated the head region of premetamorphic larvae
      of B. lanceolatum, by means of scanning electron microscopy, wholemount and
      tissue sections immunocytochemistry, and Western blotting assay, to verify the
      presence and distribution of Pit-1. Immunoreactive Pit-1 protein was detected in
      the rostral nerves and in a cluster of photoreceptor cells of the frontal eye. At
      the same time, an electrophoretic band of 33 kDa was shown from extracts of
      premetamorphic larvae and recognized by a monoclonal antibody to rat Pit-1. On
      the basis of the immunocytochemical and electrophoretic results, we can assume
      that Pit-1 may play a neuromodulatory role in the larval central nervous system.
      Moreover, the spatial and temporal distribution of Pit-1 protein in larva and
      adult lancelets agrees only in part with that described in embryonic and adult
      mice, suggesting different molecular controls of regional identity in the nervous
      system of cephalochordates and vertebrates.

PMID- 9779938
TI  - Histaminergic neurons in the sheep diencephalon.
AB  - The distribution of histaminergic neurons in the sheep brain was studied by
      immunohistochemistry by using antibodies raised against histamine. For the first
      time in this species, the presence of histamine-immunoreactive neurons was
      described in the caudal diencephalon, around the mammillary bodies, and in the
      tuberomammillary area. The general pattern of distribution of these neurons was
      similar to that described previously in other species, i.e., rodents and humans.
      The distribution in the five neuronal groups described in rodents was not easy to
      demonstrate in sheep, because the boundaries between each group were not clear.
      The labeled neurons appeared to form a continuous cell system, as in humans.
      Numerous histamine-immunoreactive mast cells were found in the habenula and the
      thalamus. Histamine-immunoreactive fibers were found in almost all of the
      structures studied. The highest density of fibers was seen in the
      tuberomammillary area, from which dense bundles of fibers ran rostrally and
      dorsally along the third ventricle in a parasagittal plane. Numerous
      immunostained fibers were found close to the wall of the ventricles; some of them
      appeared to reach the cerebrospinal fluid through the ependymal cell layer. Some
      fibers were also observed in the optic tract, and the lowest density was found in
      the supraoptic and paraventricular nuclei. These results should be useful for
      developing further physiological studies on the role of histaminergic neuronal
      systems in sheep.

PMID- 9779939
TI  - Connections of the dorsal zone of cat auditory cortex.
AB  - The present study examined the anatomic connections of the dorsal zone of cat
      auditory cortex (DZ). The DZ was discriminated physiologically from the primary
      auditory field (AI) on the basis of neuronal responses with long latency and
      broad or multipeaked tuning curves. Wheat germ agglutinin-horseradish peroxidase
      was then injected either by pressure or iontophoretically. The thalamocortical
      and corticothalamic connections of the DZ were visualized by the presence of
      retrogradely labeled neurons and anterogradely labeled terminal fields in the
      thalamus; ipsilateral corticocortical projections from other cortical fields were
      visualized by the presence of retrogradely labeled cells. Injections of tracer
      into the DZ retrogradely labeled cells mainly in the lateral division of
      posterior complex (Po) and in the dorsal division (MGd) of the medial geniculate
      body (MGB); fewer labeled cells were found in the ventral (MGv) and medial (MGm)
      divisions of the MGB and in the suprageniculate nucleus. The DZ projection to Po,
      MGv, and MGd was heavy and was more diffuse than the reciprocal thalamocortical
      projection; the projection to MGm was light. The corticothalamic terminations and
      thalamocortical cells projecting to the same part of the DZ were not superimposed
      rigidly. The DZ received cortical projections from AI and from the second,
      anterior, and posterior auditory fields, and there were strong intra-DZ
      connections. Together with the physiological findings, the present results
      suggest that the DZ is a potentially separate auditory field from AI and is
      likely to be involved in both temporal and spectral integration of acoustic
      information.

PMID- 9779940
TI  - Parvalbumin is expressed in a reciprocal circuit linking the medial geniculate
      body and auditory neocortex in the rabbit.
AB  - Recent studies of the rabbit auditory forebrain have shown that antibodies
      directed against the calcium-binding protein parvalbumin (PV) specifically
      demarcate auditory neocortex and the ventral division of the medial geniculate
      body (MGV). The auditory cortex is characterized by two PV- immunoreactive bands:
      dense terminal-like labeling within layer III/IV and a prominent band of PV+
      somata in the upper half of layer VI. In some cases, there are distinct patches
      of PV immunoreactivity within layers III/IV of auditory cortex that appear
      similar to the patchy termination of thalamocortical axons labeled by the
      injection of anterograde tracers into MGV. The presence of PV+ patches in III/IV,
      PV+ somata in layer VI, and the high density of PV+ neurons and terminals in the
      MGV suggest the existence of a reciprocal PV+ circuit linking primary auditory
      cortex (AI) and the MGV. In the present study, double-labeling experiments in
      adult rabbits were carried out to provide evidence for this circuit. Focal
      injections of the tracers biocytin or biotinylated dextran amine (BDA) into the
      MGV labeled thalamocortical afferent patches within layer III/IV and retrogradely
      labeled corticothalamic neurons in layer VIa of the ipsilateral auditory cortex.
      Adjacent sections stained with antibodies against PV revealed terminal-like PV
      immunoreactive patches in III/IV and PV+ somata in VIa that were in register with
      those labeled by BDA injections into the MGV. Serial section reconstruction of
      BDA-labeled corticothalamic neurons in VIa revealed pyramidal cells with
      tangentially oriented basal dendrites and sparsely branched apical dendrites that
      ascended to layer I. Fluorescent double-labeling studies demonstrated that a
      subpopulation of corticothalamic neurons also express PV. PV-negative
      corticothalamic neurons were also found. Discrete injections of BDA into auditory
      cortex labeled bands of neurons in the ipsilateral MGV, whose orientation
      paralleled the fibrodendritic laminae characteristic of this subdivision.
      Retrograde double-labeling experiments showed that most MGV relay neurons also
      express PV. Small numbers of PV-negative relay neurons were also found. These
      studies provide evidence for the existence of multiple, chemically coded pathways
      linking primary auditory cortex and the MGV.

PMID- 9779942
TI  - Zinc-containing afferent projections to the rat corticomedial amygdaloid complex:
      a retrograde tracing study.
AB  - The mammalian amygdaloid complex is densely innervated by zinc-containing
      neurons. The distribution of the terminals throughout the region has been
      described, but the origins of these zinc-containing fibers have not. The present
      work describes the origins of one major component of the zinc-containing
      innervation of the amygdaloid complex, namely, the component that innervates the
      corticomedial complex. Selective labeling of zinc-containing axons was
      accomplished by intracerebral microinfusion of selenium anions (SeO3(2-)), a
      procedure that produces a ZnSe precipitate in zinc-containing axonal boutons with
      subsequent retrograde transport to the neurons of origin. After infusions of
      SeO3(2-) into combinations of cortical, medial, or amygdalohippocampal regions,
      retrogradely labeled zinc-containing somata were found in all amygdaloid nuclei
      except for the medial and central nuclei, the bed nucleus of the accessory
      olfactory tract, the nucleus of the lateral olfactory tract, and the anterior
      amygdaloid area. Extrinsic zinc-containing projections to the same amygdaloid
      terminal fields were found to originate from the infralimbic, cingulate,
      piriform, perirhinal and entorhinal cortices, and from the prosubiculum and CA1.
      Commissural zinc-containing projections were found to originate from the
      posterolateral and posteromedial cortical nuclei and from the posterior part of
      the basomedial nucleus. Zinc-containing neurons have been implicated in the
      pathophysiology of epilepsy, in cell death after seizure or stroke, and in
      Alzheimer's disease, all clinical conditions that involve the amygdaloid complex.
      Identification of the zinc-containing pathways is a prerequisite to the
      elucidation of zinc's role in these disorders.

PMID- 9779941
TI  - Cerebellar microfolia and other abnormalities of neuronal growth, migration, and
      lamination in the Pit1dw-J homozygote mutant mouse.
AB  - The Snell dwarf mouse (Pit1dw-J homozygote) has a mutation in the Pit1 gene that
      prevents the normal formation of the anterior pituitary. In neonates and adults
      there is almost complete absence of growth hormone (GH), prolactin (PRL),
      thyroxin (T4), and thyroid-stimulating hormone (TSH). Since these hormones have
      been suggested to play a role in normal development of the central nervous system
      (CNS), we have investigated the effects of the Pit1dw-J mutation on the
      cerebellum and hippocampal formation. In the cerebellum, there were abnormalities
      of both foliation and lamination. The major foliation anomalies were 1) changes
      in the relative size of specific folia and also the proportional sizes of the
      anterior vs posterior cerebellum; and 2) the presence of between one and three
      microfolia per half cerebellum. The microfolia were all in the medial portion of
      the hemisphere in the caudal part of the cerebellum. Each microfolium was just
      rostral to a normal fissure and interposed between the fissure and a normal
      gyrus. Lamination abnormalities included an increase in the number of single
      ectopic granule cells in the molecular layer in both cerebellar vermis (86%) and
      hemisphere (40%) in comparison with the wild-type mouse. In the hippocampus of
      the Pit1dw-J homozygote mouse, the number of pyramidal cells was decreased,
      although the width of the pyramidal cell layer throughout areas CA1-CA3 appeared
      to be normal, but less densely populated than in the wild-type mouse. Moreover,
      the number of granule cells that form the granule cell layer was decreased from
      the wild-type mouse and some ectopic granule cells (occurring both as single
      cells and as small clusters) were observed in the innermost portion of the
      molecular layer. The abnormalities observed in the Pit1dw-J homozygote mouse seem
      to be caused by both direct and indirect effects of the deficiency of TSH (or
      T4), PRL, or GH rather than by a direct effect of the deletion of Pit1.

PMID- 9779943
TI  - Immunohistochemical localization of the mGluR1beta metabotropic glutamate
      receptor in the adult rodent forebrain: evidence for a differential distribution
      of mGluR1 splice variants.
AB  - Alternative splicing has been shown to occur at the metabotropic glutamate
      receptor 1 (mGluR1) gene. Three main isoforms that differ in their carboxy
      termini have been described so far and named mGluR1alpha, mGluR1beta and mGluR1c.
      These variants when expressed in recombinant systems all activate phospholipase
      C, although the [Ca2+] signals generated have different kinetics. Tissue
      distribution studies of specific mGluR1 splice variants are limited to the
      mGluR1alpha isoform. In the present work, we examined the localization of
      mGluR1beta in the adult rat and mouse forebrain by using a specific antipeptide
      antibody. Furthermore, the mGluR1beta immunostaining was compared with that
      obtained with antibodies specific for mGluR1alpha or with a pan-mGluR1 antibody
      which recognizes all isoforms. mGluR1beta-like immunoreactivity (LI) was found
      confined to the neuropil and neuronal perikarya and appeared discretely
      distributed in the rodent forebrain. Differential cellular distribution between
      mGluR1alpha and mGluR1beta was observed. In the hippocampus, mGluR1alpha-LI was
      restricted to non-principal neurons in all fields, whereas mGluR1beta-LI was
      strongest in principal cells of the CA3 field and dentate granule cells but
      absent in CA1. We have also shown that the vast majority of neurons in the
      striatum express mGluR1. The predominant form appeared to be mGluR1beta, with a
      distribution pattern reflecting the patch-matrix organization of the striatum.
      The specificity of the immunoreactivity described for mGluR1 splice variants was
      confirmed in mGluR1-deficient mice. The observation of a different cellular and
      regional distribution of mGluR1 splice variants, in particular in the
      hippocampus, suggests that they may mediate different roles in synaptic
      transmission.

PMID- 9779945
TI  - Brainstem inputs to the ferret medial geniculate nucleus and the effect of early
      deafferentation on novel retinal projections to the auditory thalamus.
AB  - Following specific neonatal brain lesions in rodents and ferrets, retinal axons
      have been induced to innervate the medial geniculate nucleus (MGN). Previous
      studies have suggested that reduction of normal retinal targets along with
      deafferentation of the MGN are two concurrent factors required for the induction
      of novel retino-MGN projections. We have examined, in ferrets, the relative
      influence of these two factors on the extent of the novel retinal projection. We
      first characterized the inputs to the normal MGN, and the most effective
      combination of neonatal lesions to deafferent this nucleus, by injecting
      retrograde tracers into the MGN of normal and neonatally operated adult ferrets,
      respectively. In a second group of experiments, newborn ferrets received
      different combinations of lesions of normal retinal targets and MGN afferents.
      The resulting extent of retino-MGN projections was estimated for each case at
      adulthood, by using intraocular injections of anterograde tracers. We found that
      the extent of retino-MGN projections correlates well with the extent of MGN
      deafferentation, but not with extent of removal of normal retinal targets.
      Indeed, the presence of at least some normal retinal targets seems necessary for
      the formation of retino-MGN connections. The diameters of retino-MGN axons
      suggest that more than one type of retinal ganglion cells innervate the MGN under
      a lesion paradigm that spares the visual cortex and lateral geniculate nucleus.
      We also found that, after extensive deafferentation of MGN, other axonal systems
      in addition to retinal axons project ectopically to the MGN. These data are
      consistent with the idea that ectopic retino-MGN projections develop by sprouting
      of axon collaterals in response to signals arising from the deafferented nucleus,
      and that these axons compete with other sets of axons for terminal space in the
      MGN.

PMID- 9779944
TI  - Nerve growth factor receptor TrkA is expressed by horizontal and amacrine cells
      during chicken retinal development.
AB  - Nerve growth factor is known to stimulate neurite outgrowth and support neuronal
      survival during embryonic development. We have studied the expression of the
      nerve growth factor receptor, TrkA, at both mRNA and protein levels during the
      course of chicken retinal development. Furthermore, we have compared the
      expression of trkA mRNA with that of the 75-kD low-affinity neurotrophin receptor
      (p75NTR). RNase protection assay identified peak-levels of trkA mRNA in the late
      embryonic retina. Using in situ hybridization and immunohistochemistry, we found
      cells expressing TrkA in both the internal and the external part of the inner
      nuclear layer, corresponding to amacrine and horizontal cells, respectively. The
      TrkA-expressing amacrine cell has a unistratified dendritic arborization in the
      second sublamina of the inner plexiform layer, and may represent the stellate
      amacrine cell described by Cajal. The horizontal cells, possessing arciform
      dendrite processes in the outer plexiform layer, showed strong TrkA
      immunoreactivity in both dendrites and cell bodies. During the course of retinal
      development, the TrkA-expressing amacrine cells decreased in number, whereas the
      TrkA-expressing horizontal cells persisted. Because nerve growth factor was
      expressed where the horizontal cells, but not where the amacrine cells were
      located, these findings raise the question of whether nerve growth factor could
      locally support the survival of TrkA-expressing interneurons during retinal
      development.

PMID- 9779946
TI  - Regional myocardial perfusion and mechanics: a model-based method of analysis.
AB  - A new parametric model-based method has been developed that allows epicardial
      strain distributions to be computed on the left ventricular free wall in normal
      and ischemic myocardium and integrated with the regional distributions of
      anatomic and physiological measurements so that underlying relationships can be
      explored. An array of radiopaque markers was sewn on the anterior wall of the
      left ventricle (LV) in three anesthetized open-chest canines, and their positions
      were recorded using biplane video fluoroscopy before and 2 min after occlusion of
      the left anterior descending coronary artery. The three-dimensional (3D) anatomy
      of the LV and epicardial fiber angles were measured post-mortem using a 3D probe.
      A prolate spheroidal finite element model was fitted to the epicardial surface
      points (with <0.2 mm accuracy) and fiber angles (<5 degrees error). Regional
      myocardial blood flows (MBFs) were measured using fluorescent microspheres and
      fitted into the model (<0.3 ml min(-1) g(-1) error). Epicardial fiber and cross
      fiber strain distributions were computed by allowing the model to deform from end
      diastole to end-systole according to the recorded motion of the surface markers.
      Systolic fiber strain varied from -0.05 to 0.01 within the region of the markers
      during baseline, and regional MBF varied from 1.5 to 2.0 ml min(-1) g(-1). During
      2 min ischemia, regional MBF was less than 0.3 ml min(-1) g(-1) in the ischemic
      region and 1.0 ml min(-1) g(-1) in the nonischemic region, and fiber strain
      ranged from 0.05 in the central ischemic zone to -0.025 in the remote nonischemic
      tissue. This analysis revealed a zone of impaired fiber shortening extending into
      the normally perfused myocardium that was significantly wider at the base than
      the apex. A validation analysis showed that a regularizing function can be
      optimized to minimize both fitting errors and numerical oscillations in the
      computed strain fields.

PMID- 9779947
TI  - Noninvasive delineation of normal right ventricular contractile motion with
      magnetic resonance imaging myocardial tagging.
AB  - As the importance of the right ventricle in many diseases and conditions has been
      realized, the need for quantitative assessment of the motion and contraction of
      the right ventricular free wall (RVFW) has become apparent. This study applied
      the myocardial tagging magnetic resonance imaging (MRI) technique to the normal
      RVFW to elucidate normal heterogeneity in RV motion and contractile patterns. The
      RVFW was divided into three segments (inferior, mid and superior) in each of
      three slices (apical, mid and basal) to allow for a detailed analysis of the
      motion and contraction. Percent segmental shortening (PSS) was used to measure
      the amount of contraction, and a vector analysis was used to quantitate the
      trajectory of the RVFW through systole. PSS increased monotonically through time
      to an average across all segments of 12% in the basal slice, 14% in the mid
      ventricular slice, and 16% in the apical slice of the heart. The trajectory of
      the RVFW was characterized by a wave of motion toward the septum and outflow
      tract. The data provided in this study provide a better understanding of normal
      RV kinematics and can serve as a comparison for disease states.

PMID- 9779948
TI  - Estimation of blood flow heterogeneity in human skeletal muscle using
      intravascular tracer data: importance for modeling transcapillary exchange.
AB  - Distributed models of blood-tissue exchange are widely used to measure kinetic
      events of various solutes from multiple tracer dilution experiments. Their use
      requires, however, a careful description of blood flow heterogeneity along the
      capillary bed. Since they have mostly been applied in animal studies, direct
      measurement of the heterogeneity distribution was possible, e.g., with the
      invasive microsphere method. Here we apply distributed modeling to a dual tracer
      experiment in humans, performed using an intravascular (indocyanine green dye,
      subject to distribution along the vascular tree and confined to the capillary
      bed) and an extracellular ([3H]-D-mannitol, tracing passive transcapillary
      transfer across the capillary membrane in the interstitial fluid) tracer. The
      goal is to measure relevant parameters of transcapillary exchange in human
      skeletal muscle. We show that assuming an accurate description of blood flow
      heterogeneity is crucial for modeling, and in particular that assuming for
      skeletal muscle the well-studied cardiac muscle blood flow heterogeneity is
      inappropriate. The same reason prevents the use of the common method of
      estimating the input function of the distributed model via deconvolution, which
      assumes a known blood flow heterogeneity, either defined from literature or
      measured, when possible. We present a novel approach for the estimation of blood
      flow heterogeneity in each individual from the intravascular tracer data. When
      this newly estimated blood flow heterogeneity is used, a more satisfactory model
      fit is obtained and it is possible to reliably measure parameters of capillary
      membrane permeability-surface product and interstitial fluid volume describing
      transcapillary transfer in vivo.

PMID- 9779950
TI  - Pulsatile flow in tubes of elliptic cross sections.
AB  - The compression of blood vessels by surrounding tissue is an important problem in
      hemodynamics, most prominently in studies relating to the heart. In this study we
      consider a long tube of elliptic cross section as an idealization of the geometry
      of a compressed blood vessel. An exact solution of the governing equations for
      pulsatile flow in a tube of elliptic cross section involves Mathieu functions
      which are considerably more difficult to evaluate than the Bessel functions in
      the case of a circular cross section. Results for the velocity field, flow rate
      and wall shear stress are obtained for different values of the pulsation
      frequency and ellipticity, with emphasis on how the effects of frequency and
      ellipticity combine to determine the flow characteristics. It is found that in
      general the effects of ellipticity are minor when frequency is low but become
      highly significant as the frequency increases. More specifically, the velocity
      profile along the major axis of the elliptic cross section develops sharp double
      peaks; the flow rate is reduced in approximately the same proportion as in the
      case of circular cross section; and the point of maximum shear on the tube wall
      migrates away from the minor axis where it is located in steady flow.

PMID- 9779949
TI  - Power-law kinetics of tracer washout from physiological systems.
AB  - Recent studies suggest that the tail of the washout of tracer-labeled substances
      from physiological systems can exhibit power-law behavior. In this work we
      develop a theoretical interpretation of the power-law behavior of the flow
      limited washout of tracer-labeled water from the myocardium. Using minimal
      assumptions concerning the complicated structure of the coronary network we show
      that the washout from a heterogeneous flow system is given by h(t) approximately
      equal to A x p1 (V/t)(-beta), where beta is close to 3, p1 is the probability
      density of flows through the system, V is a constant volume associated with each
      pathway, and A is a constant. This prediction fits observed power-law washout
      behavior of tracer water in the heart. This theory is general enough to lead us
      to speculate that close examination of transport in other heterogeneity-perfused
      systems is likely to reveal similar power-law behavior.

PMID- 9779951
TI  - Scaling of hemolysis in needles and catheters.
AB  - Hemolysis in clinical blood samples leads to inaccurate assay results and often
      to the need for repeated blood draws. In vitro experiments were conducted to
      determine the influence on hemolysis in phlebotomy needles and catheters of
      pressure difference, cannula diameter, and cannula material. Fresh blood from
      five human volunteers was forced from a syringe inside a pressurized chamber
      through 14, 18, and 22 gauge 304 stainless steel needles and polyurethane and
      Teflon catheters, all 40 mm long. Hemolysis was measured in the samples by a
      spectrophotometer. It was found that hemolysis increased with increases in
      pressure difference and cannula diameter and no consistent trend could be
      identified with regard to cannula material. The pressure differences required for
      significant hemolysis were above those typical of clinical venipuncture blood
      draws. While there was substantial variability among individuals, the hemolysis
      values scaled with exponent S = (t/t0)[(tau/tau0)-1]2, where t is the
      characteristic duration of shear, t0 is a time constant, tau is the wall shear
      stress, and tau0 is the wall shear stress threshold below which no hemolysis
      occurs. A hemolysis threshold including both time and shear stress was also
      defined for S = constant. The threshold implies that a threshold shear stress
      exists below which erythrocytes are not damaged for any length of exposure time,
      but that red cells may be damaged by an arbitrarily short period of exposure to
      sufficiently large shear stress.

PMID- 9779952
TI  - Development of a simulator for endovascular repair of abdominal aortic aneurysms.
AB  - The design and development of a simulator for endovascular repair of abdominal
      aortic aneurysm (AAA) is described. The simulator consists of an interchangeable
      model of a human AAA based on computed tomography data and is produced by means
      of computer-aided design and manufacture (CAD/CAM) techniques. The model has
      renal, iliac, and femoral arteries, and is perfused with a temperature controlled
      blood-analog fluid under simulated physiological flow conditions. "Fluoroscopic
      imaging" is simulated by a computerized imaging system that uses visible light. A
      movable video camera relays images in the antero-posterior and lateral planes of
      the AAA to a monitor. The imaging system allows "arteriography" and "road
      mapping" to be performed so as to facilitate accurate deployment of endovascular
      stent-grafts. The system has been used for teaching and demonstrating
      endovascular techniques to clinicians, as well as the evaluation of new stent
      graft devices. Its successful incorporation into endovascular workshops has
      demonstrated its role in the training of clinicians in endovascular repair of
      AAA.

PMID- 9779953
TI  - Blood flow and leukocyte adhesiveness are reduced in the microcirculation of a
      peritoneal disseminated colon carcinoma.
AB  - Dynamic behavior of leukocytes in the microcirculation of solid tumor tissue was
      visualized using a fluorescent labeling technique combined with the use of a real
      time confocal laser-scanning microscope (CLSM) system. Colon tumor cells (RCN-9)
      were inoculated into the peritoneal cavity of male Fischer 344 rats. Tumor-free
      rats were similarly injected with physiological saline (intraperitoneally). Ten
      days after tumor inoculation, the mesentery was exteriorized and subjected to
      vital microscopic observation under the CLSM system. Leukocytes were labeled with
      rhodamine 6G (100 microg kg(-1), intravenously), and their behavior within the
      microvessels (10-30 microm in diameter) was analyzed both in the solid tumor
      tissues and the normal mesentery. Wall shear rate was calculated from the
      measured values of vessel diameter and erythrocyte flow velocity. In tumor
      microvasculature of tumor-bearing rats, the centerline erythrocyte velocity (0.73
      +/- 0.58 mm s(-1), mean +/- standard deviation) and wall shear rate (210 +/- 151
      s(-1)) were significantly lower than those of the tumor-free rats (1.27 +/- 0.83
      mm s(-1), 344 +/- 236 s(-1), respectively). Despite such reduced flow conditions,
      flux of the rolling leukocytes as well as density of the adhered leukocytes both
      decreased significantly in tumor microvasculature as compared with normal
      controls. The methods developed in this work show promise in improving our
      understanding of tumor biology and pathophysiology.

PMID- 9779954
TI  - Comparison of theory and experiment in pulsatile flow in cat lung.
AB  - A mathematical model of pulsatile flow in cat lung based on existing morphometric
      and elastic data is presented and validated by experimental results. In the
      model, the pulmonary arteries and veins were treated as elastic tubes, whereas
      the pulmonary capillaries were treated as two-dimensional sheets. The macro- and
      microcirculatory vasculature was transformed into an analog electrical circuit.
      Input impedances of the pulmonary blood vessels of every order were calculated
      under normal physiological conditions. Pressure-flow relation of the whole lung
      was predicted theoretically. Experiments on isolated perfused cat lungs were
      carried out. The relation between pulsatile blood pressure and blood flow was
      measured. Comparison of the theoretically predicted input impedance spectra with
      those of the experimental results showed that the modulus spectra were well
      predicted, but significant differences existed in the phase angle spectra between
      the theoretical predictions and the experimental results. This latter discrepancy
      cannot be explained at present and needs to be further investigated.

PMID- 9779956
TI  - Transport phenomena in the human nasal cavity: a computational model.
AB  - Nasal inspiration is important for maintaining the internal milieu of the lung,
      since ambient air is conditioned to nearly alveolar conditions (body temperature
      and fully saturated with water vapor) on reaching the nasopharynx. We conducted a
      two-dimensional computational study of transport phenomena in model transverse
      cross sections of the nasal cavity of normal and diseased human noses for
      inspiration under various ambient conditions. The results suggest that during
      breathing via the normal human nose there is ample time for heat and water
      exchange to enable equilibration to near intraalveolar conditions. A normal nose
      can maintain this equilibrium under extreme environments (e.g., hot/humid,
      cold/dry, cold/humid). The turbinates increase the rate of local heat and
      moisture transport by narrowing the passageways for air and by induction of
      laminar swirls downstream of the turbinate wall. However, abnormal blood supply
      or mucous generation may reduce the rate of heat or moisture flux into the
      inspired air, and thereby affect the efficacy of the process.

PMID- 9779955
TI  - Oscillatory flow in a symmetric bifurcation airway model.
AB  - Flow in a symmetric bifurcation model of analytically known geometry was
      investigated experimentally under oscillatory flow conditions. The duration of
      the inspiratory and expiratory phases were set to be equal during the oscillatory
      period. A two velocity component laser Doppler anemometer was used to interrogate
      the flow field. Three different flow rates through the bifurcation were
      investigated. The peak Reynolds numbers, based on peak flow rates, were 700,
      1278, and 2077. The Womersley number was set to 4.3 and it was kept at the same
      value for the three different flow rates. The results suggest that under the
      conditions studied a quasisteady flow assumption for oscillatory flow is valid
      for only about 50% of the oscillatory period, or it is limited to represent the
      oscillatory flow only in the vicinity of peak inspiration and peak expiration.
      Complex transport phenomena that occur during the transition between the
      respiratory phases cannot be elucidated and analyzed by quasisteady equivalents.

PMID- 9779957
TI  - Influence of anisotropy on local and global measures of potential gradient in
      computer models of defibrillation.
AB  - A heart-torso model including fiber orientation is used to calculate electric
      field strength in an active-can transvenous defibrillation system and estimate
      errors due to inadequate description of the anisotropy of the myocardium. Using a
      minimum potential gradient (5 V/cm) in a critical mass (95%) of the tissue, the
      estimated defibrillation voltage threshold for a right ventricular transvenous
      lead placement differs by only 4.5% when using isotropic myocardial conductivity
      compared to a model with realistic fiber architecture. In addition, pointwise
      comparisons of the two solutions reveal differences of 10.8% rms in potential
      gradient strength and 31.6% rms in current density magnitude in the myocardium,
      resulting in a change in the location of the low gradient regions. These results
      suggest that if a minimum potential gradient throughout the heart is necessary to
      avoid reinitiation of fibrillatory wave fronts, then isotropic models are
      adequate for modeling the electric field in the heart. Alternatively, the model
      demonstrates the use of physiologically based descriptions of anisotropy and
      fiber orientation, which will soon allow simulations of shock induced membrane
      polarization during defibrillation.

PMID- 9779958
TI  - History-dependent mechanical behavior of guinea-pig small intestine.
AB  - Measurement of pressure-volume relations is a commonly used technique to
      elucidate small intestinal stiffness. There is a lack of data on the relation
      between stiffness and history-dependent mechanical properties of the
      gastrointestinal tract. We aimed to distinguish between passive properties of the
      tissue that depend on the time-history of load (viscoelastic effects) versus
      those that depend on the maximum previous load (strain softening effects). Ten
      repeated pressure-volume relations were measured at each peak pressure level in
      six isolated, passive guinea-pig jejuni in vitro during balloon inflation and
      deflation cycles. With inflation to a new higher peak pressure (ranging from 3 to
      15 mm Hg), the pressure-volume relation became less stiff, particularly in the
      low pressure range, without a significant change in unloaded jejunal volume. We
      computed the jejunal normalized volume change as a function of the integrated
      volume-time history and maximum volume. Analysis of covariance revealed
      significant dependence of the normalized volume change on the volume-time history
      (P < 0.001) and the maximum volume history (P < 0.001). Multiple linear
      regression analysis showed that approximately 90% of the history dependence could
      be attributed to the maximum volume. Most softening (loss of stiffness) happens
      in the low pressure range of the curve (0-3 mm Hg). We adopted the Johnson and
      Beatty strain softening theory and computed the volume amplification factor. This
      factor was shown to be a linear function of the normalized peak volume (r2 >
      0.999). Since strain softening effects were significantly greater than
      viscoelastic effects, we conclude that history-dependent changes in jejunal
      stiffness are more likely to involve alterations to elastic rather than viscous
      structures in the tissue. These effects must be taken into account when
      performing balloon distension studies in the gastrointestinal tract for studying
      physiological and pathophysiological problems in which loading conditions are
      altered, e.g., mechanoreceptor studies in normal intestine and in acute and
      chronic obstruction, in order to have an accurate description of the
      biomechanics.

PMID- 9779959
TI  - Optimized overcomplete signal representation and its applications to time
      frequency analysis of electrogastrogram.
AB  - The electrogastrogram (EGG) is a surface measurement of gastric myoelectrical
      activity. The normal frequency of gastric myoelectrical activity in humans is 3
      cycles/min. Abnormal frequencies in gastric myoelectrical activity have been
      found to be associated with functional disorders of the stomach. The aim of this
      article was, therefore, to develop new time-frequency analysis methods for the
      detection of gastric dysrhythmia from the EGG. A concept of overcomplete signal
      representation was used. Two algorithms were proposed for the optimization of the
      overcomplete signal representation. One was a fast algorithm of matching pursuit
      and the other was based on an evolutionary program. Computer simulations were
      performed to compare the performance of the proposed methods in comparison with
      existing time-frequency analysis methods. It was found that the proposed
      algorithms provide higher frequency resolution than the short time Fourier
      transform and Wigner-Ville distribution methods. The practical application of the
      developed methods to the EGG is also presented. It was concluded that these
      methods are well suited for the time-frequency analysis of the EGG and may also
      be applicable to the time-frequency analysis of other biomedical signals.

PMID- 9779960
TI  - Characterizing the variability of system kernel and input estimates.
AB  - The identification of the input to, or kernels of, a system using nonparametric
      representations and least-squares estimation is becoming increasingly popular.
      Nonparametric representations avoid making a priori assumptions about the input
      or having detailed knowledge about the system, and only need to guarantee known
      general characteristics (for example, positivity), which are obtained through the
      imposition of constraints on the estimates. An often overlooked problem is how to
      characterize the variability of the estimates so obtained. This problem is caused
      by the presence of constraints--and/or the nonlinearities of the estimates, or
      the complexity of the (regression based) estimation algorithms used--which make
      standard methods of estimating variability incorrect. In this article we
      investigate the use of a resampling technique called the "bootstrap" to obtain
      the desired estimates of variability. We present real data analysis demonstrating
      the approach, and through simulations we test the performance of a novel
      bootstrap technique obtaining confidence bands for the estimated functions.

PMID- 9779961
TI  - Adaptive Wiener filtering for improved acquisition of distortion product
      otoacoustic emissions.
AB  - An innovative acoustic noise canceling method using adaptive Wiener filtering
      (AWF) was developed for improved acquisition of distortion product otoacoustic
      emissions (DPOAEs). The system used one microphone placed in the test ear for the
      primary signal. Noise reference signals were obtained from three different
      sources: (a) pre-stimulus response from the test ear microphone, (b) post
      stimulus response from a microphone placed near the head of the subject and (c)
      post-stimulus response obtained from a microphone placed in the subject's nontest
      ear. In order to improve spectral estimation, block averaging of a different
      number of single sweep responses was used. DPOAE data were obtained from 11 ears
      of healthy newborns in a well-baby nursery of a hospital under typical noise
      conditions. Simultaneously obtained recordings from all three microphones were
      digitized, stored and processed off-line to evaluate the effects of AWF with
      respect to DPOAE detection and signal-to-noise ratio (SNR) improvement. Results
      show that compared to standard DPOAE processing, AWF improved signal detection
      and improved SNR.

PMID- 9779962
TI  - Orthotropic mechanical properties of chemically treated bovine pericardium.
AB  - To facilitate bioprosthetic heart valve design, especially in the use of novel
      antimineralization chemical technologies, a thorough understanding of the
      multiaxial mechanical properties of chemically treated bovine pericardium (BP) is
      needed. In this study, we utilized a small angle light scattering based tissue
      pre-sorting procedure to select BP specimens with a high degree of structural
      uniformity. Both conventional glutaraldehyde (GL) and photo-oxidation (PO)
      chemical treatment groups were studied, with untreated tissue used as the control
      group. A second set of GL and PO groups was prepared by prestretching them along
      the preferred fiber direction during the chemical treatment. An extensive biaxial
      test protocol was used and the resulting stress-strain data fitted to an
      exponential strain energy function. The high structural uniformity resulted in
      both a consistent mechanical response and low variability in the material
      constants. For free fixed tissues, the strain energy per unit volume for GL
      treated BP was approximately 2.8 times that of PO treated BP at an equibiaxial
      Green's strain level of 0.16. Pre-stretched tissues exhibited a profound increase
      in both stiffness and the degree of anisotropy, with the GL treatment
      demonstrating a greater effect. Thus, structural control leads to an improved
      understanding of chemically treated BP mechanical properties. Judicious use of
      this knowledge can facilitate the design and enhanced long-term performance of
      bioprosthetic heart valves.

PMID- 9779963
TI  - Oxalate, citrate, and sulfate concentration in human milk compared with formula
      preparations: influence on urinary anion excretion.
AB  - BACKGROUND: Nephrocalcinosis is not uncommon in preterm infants, and elevated
      urinary oxalate excretion is known to be one of the main risk factors. When
      oxalate excretion was found to be higher in formula-fed than in human milk-fed
      infants, the formulas' oxalate content was thought to be responsible. METHODS:
      The oxalate concentration in human milk (21 samples obtained during lactogenesis;
      17 samples obtained during established lactation) and of 16 formula preparations
      was examined. Citrate and sulfate concentrations were also measured, because both
      anions influence urinary saturation. RESULTS: The mean (+/- SE) oxalate content
      of human milk increased approximately 27% from early lactogenesis (70.4 +/- 6.4
      micromol/1) to established lactation (96.4 +/- 9.5 micromol/l; p < 0.05). The
      latter was not different from the mean oxalate concentration of formula (98.2 +/-
      11.4 micromol/l), however a fourfold range of measurements was recorded in both
      groups. The mean citrate content of human milk increased only slightly after
      early lactogenesis (2.66 +/- 0.22 mmol/l), but remained significantly lower than
      in formula (3.34 +/- 0.23 mmol/l; p < 0.05). The mean sulfate concentration did
      not increase and was 13 times lower in human milk (52.1 +/- 9.5 micromol/l) than
      in formula (688.7 +/- 95.4 micromol/l; p < 0.0001). CONCLUSIONS: The higher
      oxalate excretion in formula-fed infants is not because of the milk's oxalate
      concentration. Urinary citrate and sulfate excretion may be influenced by their
      higher concentrations in formula preparations, which may be of clinical
      importance in the population that is at risk for development of nephrocalcinosis.

PMID- 9779964
TI  - Selenium deficiency in tissue culture: implications for oxidative metabolism.
AB  - BACKGROUND: Selenium is located at the catalytic site of the enzyme glutathione
      peroxidase, and with selenium deficiency the activity of glutathione peroxidase
      is decreased. Cell culture is an important tool for studying oxidative processes
      that is generation and metabolism of oxygen-derived metabolites in the
      gastrointestinal system. Cell culture is also used to understand the mechanisms
      of cell injury by oxygen-derived metabolites. METHODS: To assess the importance
      of the selenium content of cell culture media, Caco-2 cells and the hepatoma
      derived cell lines, Hep3B and HepG2, were grown to confluence and placed in media
      with various concentrations of selenium. After 7 to 14 days, cells were harvested
      and assayed for glutathione peroxidase, lactate dehydrogenase, and protein
      content. RESULTS: Cells maintained in media unsupplemented with selenium
      demonstrated a progressive decrease in glutathione peroxidase activity. Cells
      maintained in media supplemented with various concentrations of selenium
      demonstrated a dose-dependent increase in glutathione peroxidase until a plateau
      was reached. The plateau was reached at approximately 400 times the selenium
      concentration routinely used in cell culture. In the Caco-2 and hepatoma cells,
      no toxicity was observed at selenium supplementation five times the lowest
      concentration needed to reach a plateau. CONCLUSIONS: Cell culture media are
      routinely deficient in selenium, and cells that are cultured in this medium are
      deficient in glutathione peroxidase activity. Studies of oxidative metabolism
      based on cultures deficient in selenium may yield results that could be falsely
      interpreted. The addition of 1 nM selenium is sufficient for these cell lines to
      reach a plateau for intracellular glutathione peroxidase activity. These
      observations may have important ramifications for the study of reactive oxygen
      metabolite injury in cell culture.

PMID- 9779965
TI  - Are intraepithelial lymphocytes in celiac mucosa responsible for inducing
      programmed cell death (apoptosis) in enterocytes? Histochemical demonstration of
      perforins in cytoplasmic granules of intraepithelial lymphocytes.
AB  - BACKGROUND: Programmed cell death refers to the genetically determined processes
      by which cells die in response to physiologic extracellular and intracellular
      signals, morphologically described as apoptosis. In physiologic and pathologic
      circumstances this process may involve effector and target cells. METHODS: To
      identify serine esterase granules in intraepithelial lymphocytes, fresh-frozen
      human small intestine mucosal sections from normal and celiac-affected mucosa
      were incubated with substrate-specific N-alpha-benzyloxy-carbonyl-L-lysine
      thiobenzyl (BLT) and a chromogen (4 Benzoylamino-2,5-diethoxybenzene-dazonium
      chloride hemi [zinc chloride] salt as capture agent and were examined by light
      microscopy. RESULTS: Normal mucosa showed an occasional intraepithelial
      lymphocyte with BLT-positive intracytoplasmic granules. Some large mononuclear
      cells of the lamina propria were similarly stained. Many more intraepithelial
      lymphocytes were BLT-positive among the surface enterocytes of untreated celiac
      mucosa. Lamina propria mononuclear cells close to the basal layer of crypt cells
      also appeared to be increased. CONCLUSIONS: The histochemical identification of
      BLT-positive esters within intraepithelial lymphocytes suggests their involvement
      in enterocyte death under physiologic conditions. The increased BLT-positive
      intraepithelial lymphocytes found in the celiac mucosa may be related to the
      known increase in cytotoxic intraepithelial lymphocytes in untreated celiac
      disease.

PMID- 9779966
TI  - Bisacodyl and high-amplitude-propagating colonic contractions in children.
AB  - BACKGROUND: The purpose of these studies was to determine the suitability of
      bisacodyl for stimulating high-amplitude-propagating contractions in pediatric
      studies of colonic manometry. METHODS: Water-perfused manometry catheters were
      inserted into the right colon of children referred for evaluations related to
      defecation disorders. Colonic motility was measured in a 3-hour test session: an
      hour fasting, an hour after a meal, and 30 minutes after administration of a
      provocative agent. RESULTS: Bisacodyl was superior to edrophonium as a stimulant
      for inducing high-amplitude-propagating contractions. Bisacodyl-induced high
      amplitude-propagating contractions were similar in amplitude, duration,
      propagation velocity, and sites of origin and extinction to naturally occurring
      high-amplitude-propagating contractions. The effect of intrarectal bisacodyl was
      similar to that of intracecal bisacodyl, except for a delay of 10 minutes in
      onset. Bisacodyl induced high-amplitude-propagating contractions in all 28
      children (22 with spontaneous high-amplitude-propagating contractions) without
      evidence of neuromuscular disease and in 2 of 9 children with a colonic
      neuromuscular disorder and no spontaneous high-amplitude-propagating
      contractions. CONCLUSIONS: Bisacodyl-induced high-amplitude-propagating
      contractions were quantitatively and qualitatively similar to naturally occurring
      high-amplitude-propagating contractions. In selected cases, such as in children
      receiving total parenteral nutrition or restricted fluid intake, it may be
      possible to shorten diagnostic colonic manometry using bisacodyl rather than
      waiting for spontaneous high-amplitude-propagating contractions.

PMID- 9779967
TI  - Anatomic variability of rejection in intestinal allografts after pediatric
      intestinal transplantation.
AB  - BACKGROUND: Rejection of the allograft is a major contributor to morbidity and
      mortality in children who undergo a small intestinal transplant. Operational
      definitions for histologic rejection have been established, but little is known
      about the anatomic variability of the histologic abnormalities. STUDY DESIGN:
      Biopsy reports were reviewed retrospectively from more than 1200 endoscopies
      performed on the 41 children who received intestinal transplantation between 1990
      and 1995. RESULTS: Biopsies were performed in the proximal jejunum and distal
      ileum allograft simultaneously on 248 occasions. In 168 biopsies, neither site
      was histologically abnormal; in 80, rejection was found. In 42, both regions were
      abnormal; however, in 17 only the jejunum was involved and in 21 the rejection
      exclusively involved the ileum. Among children whose allograft included colon,
      rejection was absent in colon and ileum in 34 biopsies, involved both in 6,
      involved ileum but not colon in another 6 and involved colon but not ileum in
      only one. When the allograft included stomach, rejection was absent in the
      stomach and jejunum 39 times, involved both sites 8 times, involved jejunum and
      not the stomach 10 times, but involved the stomach and not jejunum only once.
      Endoscopic appearance correctly predicted histologic rejection 63% of the time.
      CONCLUSION: Anatomic variability may exist in the rejection process. Sampling the
      jejunum and ileum seems to have similar sensitivity in detecting rejection,
      whereas sampling stomach and the colon is less sensitive. When allograft
      rejection is suspected on clinical grounds, sampling more than one area of the
      graft may be necessary for histologic confirmation.

PMID- 9779968
TI  - Intraduodenal lipase activity in celiac disease assessed by means of 13C mixed
      triglyceride breath test.
AB  - BACKGROUND: In patients with celiac disease, the occurrence of exocrine
      pancreatic insufficiency has been related to an impairment of the gut-mediated
      stimulatory effect of the meal on the pancreas. The purpose of this study was to
      assess the intraduodenal lipase activity in patients with celiac disease by means
      of the 13C mixed-triglyceride breath test and to monitor pancreatic function
      after the institution of a gluten-free diet. METHODS: Seventeen untreated
      patients with celiac disease (mean age, 17.4 +/- 10.5 years) were studied. After
      an overnight fast, patients were given a standard test meal consisting of 100 g
      of white bread and 0.25 g of butter per kilogram of body weight, to which 16 mg
      di-stearyl-13C-octanoyl-glyceride (mixed triglyceride) had been added. Breath
      samples were taken twice at baseline and at 30-minute intervals for 6 hours after
      the meal. 13C enrichment in breath was determined by means of Isotope Ratio Mass
      Spectrometer (IRMS) (ANCA-NT; Europa Scientific, Crewe, UK). Results were
      expressed as the maximum percentage of 13C recovery per hour at any time, the
      time to reach peak excretion of 13C, and the percentage of 13C cumulative dose
      over 6 hours. RESULTS: Mixed-triglyceride breath test results were pathologic in
      three patients and at the lower limit of the normal range in another patient. In
      the remaining 13 patients, the results were within normal values. At the 6- and
      12-month follow-ups, all patients showed normal intraduodenal lipase activity.
      CONCLUSIONS: In approximately 24% of patients with celiac disease, the
      intraduodenal pancreatic lipolytic activity is impaired. The mixed-triglyceride
      breath test could be used to assess fat maldigestion and to monitor the need for
      enzyme replacement therapy in such patients.

PMID- 9779969
TI  - Gastroesophageal reflux in preterm infants: norms for extended distal esophageal
      pH monitoring.
AB  - BACKGROUND: Preterm infants are predisposed to gastroesophageal reflux, which may
      manifest itself in many ways ranging from failure to thrive to vomiting. Extended
      distal esophageal pH monitoring is the gold standard for diagnosing reflux in the
      preterm infants and it is our objective to establish extended distal esophageal
      pH norms (reference values) for well, asymptomatic preterm infants and to compare
      with norms already established for term infants, children, adolescents, and
      adults. METHODS: Twenty-one well, asymptomatic preterm infants consuming at least
      70% of required maintenance oral feedings were recruited. The mean +/- standard
      deviation birth weight was 1549 +/- 439 g (range, 670-2470 g); the mean
      postconceptional age was 30.7 +/- 2.6 weeks (range, 25-35 weeks) and the mean
      postnatal age was 14 +/- 9 days (range, 2-40 days). Extended distal esophageal pH
      monitoring was performed on each of the infants, and the following parameters
      were calculated: reflux index, number of reflux episodes per day, number of
      reflux episodes lasting more than 5 minutes per day, and the longest recorded
      reflux episode. RESULTS: The mean reflux index was 0.7 +/- 1.1%, the mean number
      of reflux episodes per day was 7.6 +/- 11.2, the mean number of reflux episodes
      lasting more than 5 minutes per day was 0.5 +/- 1.1 and the mean longest recorded
      reflux episode was 4.2 +/- 6.1 minutes. These results were comparable to those
      seen in term infants, children, adolescents, and adults. The trends for pH norms
      according to postconceptional age and postnatal age seemed to suggest that lower
      esophageal sphincter maturation might be related to postconceptional age, but the
      differences observed were not statistically significant (p > 0.05). CONCLUSION:
      The norms (reference values) for well, asymptomatic preterm infants were
      comparable to those seen in term infants, children, adolescents, and adults. With
      the establishment of these norms, the search for a causal link between many of
      the respiratory problems encountered in prematurity and gastroesophageal reflux
      may be aided and the complications associated with gastroesophageal reflux may
      consequently be reduced.

PMID- 9779970
TI  - One-week treatment with omeprazole, clarithromycin, and metronidazole in children
      with Helicobacter pylori infection.
AB  - BACKGROUND: The efficacy of a 1-week "triple therapy" in children with
      Helicobacter pylori gastritis and recurrent abdominal pain was studied. The
      effect of treatment was also studied in correlation to recurrent abdominal pain.
      METHODS: Thirty-two children with recurrent abdominal pain were investigated with
      H. pylori serology, 13C-urea breath test, and endoscopy. Gastric biopsy specimens
      were analyzed with a rapid urease test and histopathology. H. pylori-positive
      children were treated with omeprazole, clarithromycin, and metronidazole for 7
      days. The same treatment was repeated for 2 weeks if a urea breath test produced
      positive results 1 month after the treatment period. If the test results were
      still positive after treatment, a second endoscopy was performed with culture.
      RESULTS: Twenty-eight (87.5%) children were urea breath test-negative at follow
      up 4 weeks (range, 4-15) after treatment. Another child became H. pylori-negative
      after a second treatment course. Two of the three children who were still
      positive after the two treatment periods, showed resistance to metronidazole and
      clarithromycin. CONCLUSIONS: One-week therapy with omeprazole, clarithromycin and
      metronidazole is an effective treatment in children with H. pylori infection.
      Bacterial resistance to clarithromycin and metronidazole must be monitored if
      treatment fails.

PMID- 9779971
TI  - Evaluation of iron bioavailability in infant weaning foods fortified with haem
      concentrate.
AB  - BACKGROUND: Nutritional iron deficiency in infants over 4 months of age is one of
      the most common deficiency disorders. Dietary iron is comprised of non-haem and
      haem iron, the latter being absorbed by a separate pathway and more efficiently
      than non-haem iron. Fortification of infant weaning foods is one of the
      strategies adopted for preventing iron deficiency and the aim of this project was
      to examine the potential use of haem iron concentrate as a fortificant. METHODS:
      Sixteen non-anaemic 6-month old infants were recruited and allocated to two
      groups of 8. Each infant consumed 2 meals/day of a commercial weaning food (100
      g) for 7 consecutive days containing 40 mg ascorbic acid and 2.5 mg haem iron/100
      g (Group 1) or the same quantity of iron as ferrous sulphate plus 40 mg ascorbic
      acid (Group 2). Bioavailability was assessed by chemical balance using carmine to
      mark the beginning and end of the faecal collection. The effect of haem iron
      concentrate (as a candidate for the factor in meat that enhances iron absorption)
      was examined by measuring its effect on 57Fe-labelled non-haem iron absorption.
      RESULTS: There was no difference in iron balance between the two groups. Mean
      iron retention was 3.5 (SD 2.1) mg/day in Group 1 (haem iron) and 3.0 (SD 2.4)
      mg/day in Group 2 (ferrous sulphate). Haem concentrate did not enhance the
      absorption of 57Fe-labelled non-haem iron, Group 1: 1710 (SD 11.1)%, Group 2:
      28.4 (SD 17.7)%. CONCLUSIONS: Haem iron concentrate appears to be a highly
      bioavailable form of iron when added to infant weaning foods. This protein is
      not, however, responsible for the enhancing effect of animal protein on non-haem
      iron absorption.

PMID- 9779973
TI  - Clinical quiz. Celiac disease.

PMID- 9779972
TI  - High absorption of fortification iron from current infant formulas.
AB  - BACKGROUND: Estimations of iron absorption from infant formulas are based on 20
      year-old data. Data about iron bioavailability from currently used infant
      formulas are scarce, considering that during the last decades, formulas have had
      modifications that could affect iron absorption. METHODS: Bioavailability of
      isotopically labeled iron (55Fe and 59Fe) from several infant formulas
      administered to contraceptive-using women between the ages of 30 to 50 years was
      measured. Six infant formulas and one follow-on formula were compared with a
      powdered, whole cow's milk, and the results were normalized to an absorption of
      40% from a reference dose of iron. RESULTS: Iron bioavailability from the infant
      formulas was consistently higher (19%), contrasting with the low value (4%) of
      the unmodified cow's milk (p < 0.0001). Iron absorption of the follow-on formula
      was intermediate (13%). Formulas with 8 mg/l iron and one with 7 mg/l supply
      approximately 1 mg of absorbed iron, assuming a consumption of 750 ml/day of
      formula. This amount covers the iron needs of most infants during their period of
      greatest vulnerability. Formulas containing 12 mg/l iron would allow the
      absorption of approximately twice the infant iron requirements. CONCLUSIONS:
      Current infant formulas have a high iron bioavailability, which is an appealing
      argument for lowering the level of iron fortification in these products.

PMID- 9779974
TI  - Electrogastrography: its role in managing gastric disorders.

PMID- 9779976
TI  - Endoscopic cure of pancreatic pseudocyst in a child.

PMID- 9779975
TI  - Acute gallbladder distension and recurrent small bowel intussusception in a child
      with celiac disease.

PMID- 9779977
TI  - Retroperitoneal lymphadenopathy and mesenteric mass mimicking lymphoma in a child
      with celiac disease.

PMID- 9779978
TI  - Nodular duodenum after pediatric renal transplant due to Brunner's gland
      hyperplasia.

PMID- 9779979
TI  - Aluminum in large and small volume parenterals used in total parenteral
      nutrition: response to the Food and Drug Administration notice of proposed rule
      by the North American Society for Pediatric Gastroenterology and Nutrition.

PMID- 9779980
TI  - Cell signaling: an overview.

PMID- 9779981
TI  - Cell growth control by G protein-coupled receptors: from signal transduction to
      signal integration.

PMID- 9779982
TI  - Tyrosine kinase receptor-activated signal transduction pathways which lead to
      oncogenesis.
AB  - Oncogenesis is a complicated process involving signal transduction pathways that
      mediate many different physiological events. Typically, oncogenes cause
      unregulated cell growth and this phenotype has been attributed to the growth
      stimulating activity of oncogenes such as ras and src. In recent years, much
      research effort has focused on proteins that function downstream of Ras, leading
      to the identification of the Ras/Raf/MAPK pathway, because activation of this
      pathway leads to cellular proliferation. Activated receptor tyrosine kinases
      (RTKs) also utilize this pathway to mediate their growth-stimulating effects.
      However, RTKs activate many other signaling proteins that are not involved in the
      cellular proliferation process, per se and we are learning that these pathways
      also contribute to the oncogenic process. In fact, RTKs and many of the proteins
      involved in RTK-dependent signal transduction can also function as oncogenes. For
      example, the catalytic subunit of phosphoinositide 3-kinase (P13-K) was recently
      identified as an oncogenic protein. The scope of pathways that are activated by
      oncogenic RTKs is expanding. Thus, not only do RTKs activate Ras-dependent
      pathways that drive proliferation, RTKs activate P13-K-dependent pathways which
      also contribute to the oncogenic mechanism. P13-K can initiate changes in gene
      transcription, cytoskeletal changes through beta-catenin, changes in cell
      motility through the tumor suppressor, adenomatous polyposis coli (APC), and
      phosphorylation of BAD, a protein involved in apoptotic and antiapoptotic
      signaling. There is also cross-talk between RTKs and the oncostatin cytokine
      receptor which may positively and negatively influence oncogenesis. For this
      review, we will focus on oncogenic RTKs and the network of cellular proteins that
      are activated by RTKs because multiple, divergent pathways are responsible for
      oncogenesis.

PMID- 9779983
TI  - Antigen receptor signaling: integration of protein tyrosine kinase functions.
AB  - Antigen receptors on T and B cells function to transduce signals leading to a
      variety of biologic responses minimally including antigen receptor editing,
      apoptotic death, developmental progression, cell activation, proliferation and
      survival. The response to antigen depends upon antigen affinity and valence,
      involvement of coreceptors in signaling and differentiative stage of the
      responding cell. The requirement that these receptors integrate signals that
      drive an array of responses may explain their evolved structural complexity.
      Antigen receptors are composed of multiple subunits compartmentalized to provide
      antigen recognition and signal transduction function. In lieu of on-board
      enzymatic activity these receptors rely on associated Protein Tyrosine Kinases
      (PTKs) for their signaling function. By aggregating the receptors, and hence
      their appended PTKs, antigens induce PTK transphosphorylation, activating them to
      phosphorylate the receptor within conserved motifs termed Immunoreceptor Tyrosine
      based Activation Motifs (ITAMs) found in transducer subunits. The tyrosyl
      phosphorylated ITAMs then interact with Src Homology 2 (SH2) domains within the
      PTKs leading to their further activation. As receptor phosphorylation is
      amplified, other effectors, such as Shc, dock by virtue of SH2 binding, and
      serve, in-turn, as substrates for these PTKs. This sequence of events not only
      provides a signal amplification mechanism by combining multiple consecutive steps
      with positive feedback, but also allows for signal diversification by
      differential recruitment of effectors that provide access to distinct parallel
      downstream signaling pathways. The subject of antigen receptor signaling has been
      recently reviewed in depth (DeFranco, 1997; Kurosaki, 1997). Here we discuss the
      biochemical basis of antigen receptor signal transduction, using the B cell
      receptor (BCR) as a paradigm, with specific emphasis on the involved PTKs. We
      review several specific mechanisms by which responses through these receptors are
      propagated and modified by accessory molecules, and discuss how signal
      amplification and diversification are achieved.

PMID- 9779984
TI  - Signaling by integrin receptors.
AB  - Adhesive interactions are critical for the proliferation, survival and function
      of all cells. Integrin receptors as the major family of adhesion receptors have
      been the focus of study for more than a decade. These studies have tremendously
      enhanced our understanding of the integrin-mediated adhesive interactions and
      have unraveled novel integrin functions in cell survival mechanisms and in the
      activation of divergent signaling pathways. The signals from integrin receptors
      are integrated from those originating from growth factor receptors in order to
      organize the cytoskeleton, stimulate cell proliferation and rescue cells from
      matrix detachment-induced programmed cell death. These functions are critical in
      the regulation of multiple processes such as tissue development, inflammation,
      angiogenesis, tumor cell growth and metastasis and programmed cell death.

PMID- 9779985
TI  - Genetic analysis of mammalian G-protein signalling.
AB  - Heterotrimeric G-proteins are important signalling proteins which function in all
      cells of the mammalian organism. Inactivating mutations in a variety of G-protein
      alpha-subunit genes in mice resulted in mostly unexpected phenotypes and have
      provided interesting new insight into their biological roles. Whereas the
      inactivation of some G alpha genes led to mild phenotypes suggesting the presence
      of redundant or compensatory mechanisms, other G-proteins appear to play highly
      specific biological or developmental roles. The purpose of this review is to
      summarize the current knowledge about G-protein functions based on gene
      inactivation studies.

PMID- 9779986
TI  - Regulation of cell proliferation by G proteins.
AB  - G Proteins provide signal transduction mechanisms to seven transmembrane
      receptors. Recent studies have indicated that the alpha-subunits as well as the
      betagamma-subunits of these proteins regulate several critical signaling pathways
      involved in cell proliferation, differentiation and apoptosis. Of the 17 alpha
      subunits that have been cloned, at least ten of them have been shown to couple
      mitogenic signaling in fibroblast cells. Activating mutations in G alpha(s), G
      alpha(i)2, and G alpha12 have been correlated with different types of tumors. In
      addition, the ability of the betagamma-subunits to activate mitogenic pathways in
      different cell-types has been defined. The present review briefly summarizes the
      diverse and novel signaling pathways regulated by the alpha- as well as the
      betagamma-subunits of G proteins in regulating cell proliferation.

PMID- 9779987
TI  - Increasing complexity of Ras signaling.
AB  - The initial discovery that ras genes endowed retroviruses with potent
      carcinogenic properties and the subsequent determination that mutated ras genes
      were present in a wide variety of human cancers, prompted a strong suspicion that
      the growth-promoting actions of mutated Ras proteins contribute to their aberrant
      regulation of growth stimulatory signaling pathways. In 1993, a remarkable
      convergence of experimental observations from genetic analyses of Drosophila, S.
      cerevisiae and C. elegans as well as biochemical and biological studies in
      mammalian cells came together to define a clear role for Ras in signal
      transduction. What emerged was an elegant linear signaling pathway where Ras
      functions as a relay switch that is positioned downstream of cell surface
      receptor tyrosine kinases and upstream of a cytoplasmic cascade of kinases that
      included the mitogen-activated protein kinases (MAPKs). Activated MAPKs in turn
      regulated the activities of nuclear transcription factors. Thus, a signaling
      cascade where every component between the cell surface and the nucleus was
      defined and conserved in worms, flies and man. This was a remarkable achievement
      in our efforts to appreciate how the aberrant function of Ras proteins may
      contribute to the malignant growth properties of the cancer cell. However, the
      identification of this pathway has proven to be just the beginning, rather than
      the culmination, of our understanding of Ras in signal transduction. Instead, we
      now appreciate that this simple linear pathway represents but a minor component
      of a very complex signaling circuitry. Ras signaling has emerged to involve a
      complex array of signaling pathways, where cross-talk, feedback loops, branch
      points and multi-component signaling complexes are recurring themes. The simplest
      concept of a signaling cascade, where each component simply relays the same
      message to the next, is clearly not the case. In this review, we summarize our
      current understanding of Ras signal transduction with an emphasis on new
      complexities associated with the recognition and/or activation of cellular
      effectors, and the diverse array of signaling pathways mediated by interaction
      between Ras and Ras-subfamily proteins with multiple effectors.

PMID- 9779988
TI  - Rho family proteins and Ras transformation: the RHOad less traveled gets
      congested.
AB  - The Rho family of small GTPases has attracted considerable research interest over
      the past 5 years. During this time, we have witnessed a remarkable increase in
      our knowledge of the biochemistry and biology of these Ras-related proteins.
      Thus, Rho family proteins have begun to rival, if not overshadow, interest in
      their more celebrated cousins, the Ras oncogene proteins. The fascination in Rho
      family proteins is fueled primarily by two major observations. First, like Ras,
      Rho family proteins serve as guanine nucleotide-regulated binary switches that
      control signaling pathways that in turn regulate diverse cellular processes. Rho
      family proteins are key components in cellular processes that control the
      organization of the actin cytoskeleton, activate kinase cascades, regulate gene
      expression, regulate membrane trafficking, promote growth transformation and
      induce apoptosis. Second, at least five Rho family proteins have been implicated
      as critical regulators of oncogenic Ras transformation. Thus, it is suspected
      that Rho family proteins contribute significantly to the aberrant growth
      properties of Ras-transformed cells. Rho family proteins are also critical
      mediators of the transforming actions of other transforming proteins and include
      Dbl family oncogene proteins, G protein-coupled receptors and G protein alpha
      subunits. Thus, Rho family proteins may be key components for the transforming
      actions of diverse oncogene proteins. Major aims of Rho family protein studies
      are to define the molecular mechanism by which Rho family proteins regulate such
      a diverse spectrum of cellular behavior. These efforts may reveal novel targets
      for the development of anti-Ras and anti-cancer drugs.

PMID- 9779989
TI  - Non-Ras targets of farnesyltransferase inhibitors: focus on Rho.
AB  - Farnesyltransferase inhibitors (FTIs) are a novel class of cancer therapeutics
      whose development was based on the discovery that the function of oncogenic Ras
      depends upon its posttranslational farnesylation. Significantly, experiments in
      animal models have shown that FTIs have promise as nontoxic cancer therapeutics.
      However, cell biological studies have suggested that FTIs may act at a level
      beyond that of suppressing Ras function, so the exact mechanism of action has
      emerged as a question of major interest. Here, we review evidence that proteins
      other than Ras are important targets for inhibition, summarize findings
      suggesting a role for farnesylated Rho proteins prompted by studies on RhoB, and
      suggest a new model for how FTIs exert their biological effects. The 'FTI-Rho
      hypothesis' proposes that FTIs act in part by altering Rho-dependent cell
      adhesion signals which are linked to pathways controlling cell cycle and cell
      survival and which are subverted or defective in neoplastic cells. This model
      offers a novel framework for addressing the questions about FTI biology,
      including the basis for lack of toxicity to normal cells, cytotoxic versus
      cytostatic effects on tumor cells, and the persistence and drug resistance of
      malignant cells in FTI-treated animals.

PMID- 9779990
TI  - Signaling by dual specificity kinases.
AB  - Dual specificity kinases that phosphorylate the Thr- and Tyr-residues within the
      TXY motif of MAP-kinases of play a central role in the regulation of various
      processes of cell growth. These dual specificity kinases also known as MAP kinase
      kinases are constituents of the sequential kinase signaling modules. Seven
      distinct mammalian MAP kinases kinases have been identified. Some of the unique
      signaling properties of these kinases are discussed here.

PMID- 9779991
TI  - Cell cycle targets of Ras/Raf signalling.
AB  - The regulation of cell proliferation in multicellular organisms is a complex
      process, which is primarily regulated by external growth factors provided by
      surrounding cells. Once induced to proliferate, the passage through the mitotic
      cell cycle is directed by the components of the so called cell cycle machinery.
      Over the last years research on growth factor signal-transduction and the
      components of the cell cycle system has lead to a detailed knowledge of the
      mechanisms by which growth factors transmit their signals and of the relationship
      between the components of the cell cycle machinery. The remaining question how
      the growth factor mediated signal-transduction cascades couple with the cell
      cycle regulators has recently been a focus of interest.

PMID- 9779992
TI  - The many faces of Src: multiple functions of a prototypical tyrosine kinase.
AB  - c-src was first isolated as the normal cellular homologue of v-src, the
      transforming gene of Rous Sarcoma virus (Stehelin et al., 1976). As the first
      proto-oncogene described and one of the first molecules demonstrated to have
      tyrosine kinase activity, Src has provided a prototype for understanding signal
      transduction involving tyrosine phosphorylation. Comparison between c-src and
      activated or transforming mutants of Src including v-src, combined with recent
      data on the structure of Src family kinases has provided new insight into their
      regulation. In this review, I will discuss the function of the various domains of
      Src in light of these mutational and structural studies.

PMID- 9779993
TI  - From Src Homology domains to other signaling modules: proposal of the 'protein
      recognition code'.
AB  - The study of oncogenes has illuminated many aspects of cellular signaling. The
      delineation and characterization of protein modules exemplified by Src Homology
      domains has revolutionized our understanding of the molecular events underlying
      signal transduction pathways. Several well characterized intracellular modules
      which mediate protein-protein interactions, namely SH2, SH3, PH, PTB, EH, PDZ,
      EVH1 and WW domains, are directly involved in the multitude of membrane,
      cytoplasmic and nuclear processes in multicellular and/or unicellular organisms.
      The modular character of these protein domains and their cognate motifs, the
      universality of their molecular function, their widespread occurrence, and the
      specificity as well as the degeneracy of their interactions have prompted us to
      propose the concept of the 'protein recognition code'. By a parallel analogy to
      the universal genetic code, we propose here that there will be a finite set of
      precise rules to govern and predict protein-protein interactions mediated by
      modules. Several rules of the 'protein recognition code' have already emerged.

PMID- 9779994
TI  - Anti-apoptotic versus pro-apoptotic signal transduction: checkpoints and stop
      signs along the road to death.
AB  - The activation of caspases is a final commitment step for apoptosis. It is now
      evident that signal transduction pathways involving specific protein kinases
      modulate the apoptotic response. Both pro-apoptotic and anti-apoptotic pathways
      integrate environmental cues that control the decision to undergo apoptosis. Pro-
      and anti-apoptotic signal pathways regulate the activation of the caspases. In
      this review we describe our current understanding of apoptotic signal
      transduction.

PMID- 9779995
TI  - Stress-activated kinases regulate protein stability.
AB  - Proteasome inhibitors have been used to demonstrate that many proteins of the
      signal transduction pathways are regulated by degradation via the ubiquitin
      proteasome pathway. The key question is what events target specific proteins for
      ubiquitination at one time and prevent ubiquitination at other times? In this
      review, we develop the notion that there is a direct relationship between the
      phosphorylation/dephosphorylation cascade of the signal transduction pathways and
      the targeting of the regulatory proteins for ubiquitination. We present examples
      where phosphorylation appears to alter the interaction between the targeting
      systems and the substrate by modifying the targeting system, the substrate, or
      both. These interacting systems are seen in the response of p53, c-jun and ATF-2
      in cells subjected to stress or DNA damage and to the normal regulated response
      in a variety of pathways including the IkappaB-NFkappaB and JAK-STAT pathways.
      The interweaving of the two post-translational networks, phosphorylation and
      ubiquitination, provides a powerful insight into global regulatory control
      pathways.

PMID- 9779996
TI  - Impairment of cell adhesion by expression of the mutant neurofibromatosis type 2
      (NF2) genes which lack exons in the ERM-homology domain.
AB  - Neurofibromatosis 2 (NF2) is an inherited disorder characterized by a
      predisposition to multiple intracranial tumors. The protein encoded by the NF2
      gene has striking similarities to ezrin, radixin and moesin (ERM) proteins which
      link membrane proteins to the cytoskeleton. Therefore, it can be speculated that
      the disruption of cytoskeletal organization by alterations in the NF2 gene is
      involved in the development of tumors. It has been reported that the majority of
      NF2 mutations were nonsense or frameshift mutations that result in premature
      termination of translation. To facilitate the detection of these mutations, we
      performed protein truncation test and found that 11 of 14 NF2 patients had
      truncational mutations (79%). Seven of the 11 patients (64%) had a splicing
      abnormality which lead to absence of exons in the ERM homology domain. To examine
      the biological significance of the exon-missing mutations in the ERM homology
      domain, we expressed the wild-type (wt-NF2) and the various mutant NF2s (mu-NF2s)
      in a fibroblast cell line by using both liposome-mediated transfection and
      nuclear microinjection of the expression plasmids. The wt-NF2 showed intense
      punctate staining in the perinuclear cytoplasm in addition to overall staining of
      the submembranous area, whereas the mu-NF2s lacking exons in the ERM homology
      domain showed granular staining at the perinuclear region without any
      accumulation at the submembrane region. Microinjection of wt-NF2 cDNA into the
      nucleus of VA13 cells revealed that wt-NF2 protein induced a progressive
      elongation of cell processes. Furthermore, cells that expressed mu-NF2 had
      decreased adhesion, which resulted in detachment from the substratum. These
      findings suggested that the exon-missing mutations in the ERM-homology domain may
      affect cell membrane-cytoskeleton signaling and consequently disrupt cell-to-cell
      or cell-to-matrix interaction.

PMID- 9779997
TI  - An anti-sense construct of full-length ATM cDNA imposes a radiosensitive
      phenotype on normal cells.
AB  - The cloning of a full-length cDNA for the gene (ATM) mutated in the human genetic
      disorder ataxia-telangiectasia (A-T) has been described recently. This cDNA, as
      well as a fragment representing a functional region from ATM, are capable of
      rescuing various aspects of the radiosensitive phenotype in A-T cells. We have
      subcloned full-length ATM cDNA in the opposite orientation in an EBV-based vector
      under the control of an inducible promoter to determine whether this anti-sense
      construct might sensitize control lymphoblastoid cells to ionizing radiation. The
      effectiveness of expression of this construct in control cells was monitored by
      loss of ATM protein which was evident over a period 6-12 h after induction. Under
      these conditions radiosensitivity was enhanced approximately threefold in control
      cells, approaching the degree of radiosensitivity observed in A-T cells.
      Expression of the anti-sense construct also increased the number of radiation
      induced chromosomal breaks and led to the appearance of radioresistant DNA
      synthesis in these cells. Abrogation of the G1/S checkpoint was evident from the
      loss of the p53 response and that of its downstream effector, p21/WAF1, post
      irradiation. The extent of accumulation of transfected cells in G2/M phase at 24
      h post-irradiation was similar to that observed in A-T cells and the induction of
      stress-activated protein kinase by ionizing radiation was prevented by antisense
      ATM cDNA expression. These data demonstrate that full-length ATM anti-sense cDNA,
      by reducing the amount of ATM protein, is effective in imposing a series of known
      defects characteristic of the A-T phenotype. This inducible system provides an
      experimental model to further investigate mechanisms underlying radiosensitivity
      and cell cycle control.

PMID- 9779998
TI  - p53 induces angiogenesis-restricted dormancy in a mouse fibrosarcoma.
AB  - The p53 tumor-suppressor gene is inactivated in over 50% of all human cancers. In
      normal cells, p53 induces growth arrest and apoptosis in response to DNA damage.
      We show that p53 acts as potent tumor-suppressor gene independent of its well
      documented effects on tumor-cell proliferation and apoptosis. p53 activates
      target genes in a murine fibrosarcoma cell-line but does not affect tumor cell
      cycle progression or survival. Exogenous expression of wt-p53 does, however,
      block the angiogenic potential of the tumor cells resulting in formation of
      dormant tumors in vivo. These data provide evidence that: (1) p53 acts as a tumor
      suppressor gene independent of its anti-proliferative effects; (2) By inhibiting
      angiogenesis p53 can indirectly induce apoptosis in vivo but not in vitro; (3)
      p53-gene therapy which alters a tumors angiogenic potential, can revert tumors to
      a dormant phenotype.

PMID- 9779999
TI  - Peptide containing the BCR oligomerization domain (AA 1-160) reverses the
      transformed phenotype of p210bcr-abl positive 32D myeloid leukemia cells.
AB  - We first showed that the introduction of a bcr-abl transcription unit into the
      32D murine myeloid cell line (P210bcrabl32D) converts this cell line from an IL3
      dependent cell line to an IL3 growth independent cell line. We next cloned a
      fragment of the bcr-abl cDNA, which codes for the bcr oligomerization domain and
      neighboring regions. To test for a transformation inhibitory effect of this
      oligomerization inhibitory peptide transcription unit on the p210bcr-abl mediated
      IL3 independent growth of the P210bcrabl32D cell line, we transiently co
      electroporated into the growth factor dependent 32D cells, mixtures of plasmids
      which contained varying ratios of the plasmid expression vectors for the bcr
      oligomerization inhibitory peptide along with a smaller amount of the plasmid
      expression vector for the full length p210bcr-abl. (The P210bcr-abl protein
      converts the 32D from a growth factor dependent into a growth factor independent
      cell line.) We then showed that the oligomerization domain containing fragment
      from the bcr and bcr-abl proteins, can be used to inhibit the IL3 independent
      growth of p210bcr-abl positive 32D cells. These studies may be of eventual
      interest for those investigators whose goal is to design molecular therapeutic
      approaches to CML based on the use of peptidomimetic chemical functionalities,
      which mimic the structure and the inhibitory binding properties of the
      oligomerization domain containing fragment so as to inhibit the transforming
      function of the P210bcr-abl oncoprotein.

PMID- 9780000
TI  - Mammalian base excision repair by DNA polymerases delta and epsilon.
AB  - Two distinct pathways for completion of base excision repair (BER) have been
      discovered in eukaryotes: the DNA polymerase beta (Pol beta)-dependent short
      patch pathway that involves the replacement of a single nucleotide and the long
      patch pathway that entails the resynthesis of 2-6 nucleotides and requires PCNA.
      We have used cell extracts from Pol beta-deleted mouse fibroblasts to separate
      subfractions containing either Pol delta or Pol epsilon. These fractions were
      then tested for their ability to perform both short- and long-patch BER in an in
      vitro repair assay, using a circular DNA template, containing a single abasic
      site at a defined position. Remarkably, both Pol delta and Pol epsilon were able
      to replace a single nucleotide at the lesion site, but the repair reaction is
      delayed compared to single nucleotide replacement by Pol beta. Furthermore, our
      observations indicated, that either Pol delta and/or Pol epsilon participate in
      the long-patch BER. PCNA and RF-C, but not RP-A are required for this process.
      Our data show for the first time that Pol delta and/or Pol epsilon are directly
      involved in the long-patch BER of abasic sites and might function as back-up
      system for Pol beta in one-gap filling reactions.

PMID- 9780001
TI  - p53 is involved in regulation of the DNA repair gene O6-methylguanine-DNA
      methyltransferase (MGMT) by DNA damaging agents.
AB  - The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) is inducible
      by genotoxic stress. MGMT induction results from transcriptional activation of
      the MGMT gene which is a specific response to DNA damage. A possible factor
      involved in triggering MGMT induction might be p53, because both p53 and MGMT are
      activated by DNA breaks. To study the effect of p53 on induction of the MGMT
      gene, we compared the presence of functional wild-type (wt) and mutant p53 with
      MGMT expression level in various mouse fibroblasts and rat hepatoma cell lines
      upon genotoxic treatment. Cells which responded to ionizing radiation (IR) by
      MGMT induction displayed functional p53, whereas in cells not expressing wt p53,
      MGMT induction was not observed. Also, the cloned MGMT promoter was inducible by
      IR upon transfection into p53 wt cells, but not in cells deficient for p53. Thus,
      expression of wt p53 appears to be required for induction of MGMT mRNA and
      protein by IR. On the other hand, transfection of a MGMT-promoter-CAT construct
      together with p53 (either wt or mutant) in cells expressing wt p53 markedly
      reduced the basal activity of the MGMT promoter whereas cotransfection with a p53
      antisense construct slightly increased MGMT promoter activity. Furthermore,
      cotransfection of MGMT promoter with wt or mutant p53 in p53 wt cells reduced
      radiation evoked MGMT promoter induction. Thus, transfection mediated high level
      expression of p53 has inhibitory effect both on basal MGMT promoter activity and
      its activation by IR. The results give evidence for involvement of p53 in DNA
      damage-induced MGMT promoter activation.

PMID- 9780002
TI  - A novel E2F binding protein with Myc-type HLH motif stimulates E2F-dependent
      transcription by forming a heterodimer.
AB  - The human embryonal carcinoma cells NEC14 can be induced to differentiate
      morphologically by the addition of 10(-2) M N, N'-hexamethylene-bis-acetamide and
      cease to grow in several days. Transcription factors of the E2F/DP family have
      been shown to be closely related to the regulation of cell proliferation. To
      analyse cellular proteins which interact with E2F in NEC14 cells, cDNA clones
      encoding E2F binding proteins were isolated from a lambdaZAP II NEC14 cell
      library with the 32P-labeled GST (Glutathione S-transferase)-E2F-1 fusion protein
      as a probe. One of the clones encodes E2FBP1 which has the helix-loop-helix (HLH)
      motif, but lacks the basic domain and the zipper structure usually found at N-
      and C-terminal sides to the HLH motif, respectively. The arrangement of amino
      acids in the helix 1 and helix 2 regions is quite similar to those of Mxi and
      Mad, but different from those of E2F-1 and DP-1. Western blot analysis of the
      immunoprecipitates prepared with anti-E2FBP1 antibody showed that E2FBP1
      associates with both E2F-1 and DP-1 in vivo. E2FBP1 alone has no DNA binding
      activity, but bind to the E2F site through heterodimerization with E2F-1 but not
      with DP-1. Although E2FBP1 lacks the transactivation domain, it stimulates E2F
      site-dependent transcription in cooperation with E2F-1.

PMID- 9780004
TI  - Oncogene-induced up-regulation of Caco-2 cell proliferation involves IGF-II gene
      activation through a protein kinase C-mediated pathway.
AB  - We previously reported that ras and polyoma middle T (PyMT), a constitutive
      activator of the src protooncogene product, up-regulated Caco-2 cell
      proliferation along with protein kinase C (PKC) alpha expression and PKC
      activity. We aimed to investigate whether oncogene-induced up-regulation of Caco
      2 cell proliferation involved stimulation of the autocrine IGF-II/IGF-I receptor
      (IGFIR) loop described in these cells and if so, to analyse the role of
      overexpressed and activated PKC. Compared with control vector transfected Caco-2
      cells, ras- and PyMT-transfected cells exhibited increased expression of the 6.0
      and 4.8 kb IGF-II transcripts. This was due to increased activity of the P3 and
      P4 promoters of the IGF-II gene which correlated with increased expression and
      DNA-binding activity of Sp1, a transcription factor interacting with several
      specific sites in P3 and P4 promoters. Oncogene-transfected cells displayed
      enhanced autocrine IGF-II production, which was fully responsible for the
      oncogene-induced increase in their proliferation since this increase was blunted
      by anti-human IGF-II and IGF1R (alphaIR3) antibodies. PKC mediated oncogene
      activation of the IGF-II gene presumably through action on Sp1 since (i) PKC
      activation by phorbol 12-myristate 13-acetate increased Sp1 expression, P3 and P4
      activity and IGF-II mRNA in control but not in oncogene-transfected cells; and
      (ii) PKC inhibition by the PKC inhibitor Go6976 reduced Sp1, P3 and P4 activity
      and IGF-II mRNA in all three cell lines. This is the first evidence that ras- and
      PyMT/src oncogenes up-regulate Caco-2 cell proliferation through a PKC-mediated
      pathway which stimulates IGF-II gene transcription and thereby increases
      autocrine IGF-II production. The mechanisms underlying IGF-II gene activation by
      PKC most probably involve action on Sp1.

PMID- 9780003
TI  - The E2F-family proteins induce distinct cell cycle regulatory factors in p16
      arrested, U343 astrocytoma cells.
AB  - We previously demonstrated that P16Ink4a (p16) expression in p16-deficient U343
      astrocytoma cells causes a G1 cell cycle arrest, profound changes in cytoskeletal
      proteins and alterations in expression and activity of the pRB and E2F family
      proteins. We examine here the effects of expressing wild type or mutant versions
      of the downstream targets of p16 in U343 astrocytomas. We first attempted to
      block proliferation of U343 cells using the dominant mutant of pRB, deltap34.
      Expression of this mutant in the human osteosarcoma, SAOS-2, potently blocked
      proliferation but did not affect the cell cycle of U343 cells. We next showed
      that expression of E2F-1, E2F-2, E2F-3 and E2F-4 are each able to overcome this
      p16-dependent cell cycle arrest but exhibit distinct biological activities.
      Adenoviral-mediated expression of E2F-1, E2F-2, E2F-3, or E2F-4 overcame the p16
      dependent cell cycle block and induced alterations in cell morphology. E2F-5,
      only in conjunction with DP1, promoted cell cycle progression. For both E2F-1 and
      E2F-2, but not E2F-3 or E2F-5/DP1, cell cycle re-entry was associated with almost
      quantitative cell death. Only small numbers of dying cells were observed in E2F-4
      expressing cultures. Expression of the different E2F's altered the expression of
      distinct sets of cell cycle regulatory proteins. E2F-1 induced endogenous E2F-4
      expression and also caused an increase in pRB, p107 and cyclin E levels.
      Expression of E2F-4 caused a weak increase in E2F-1 levels but also strongly
      induced pRB, p107, p130 and cyclin E. However, E2F-1 and E2F-4 clearly regulate
      expression of distinct genes, demonstrated when E2F-4 caused a threefold increase
      in the levels of cdk2 whereas E2F-1 failed to increase in this cyclin dependent
      kinase. Similarly, expression of E2F-1 or E2F-2 were shown to have distinct
      effects on the expression of cdk2, cyclin E and pRB despite both of these closely
      related E2F-family members potently inducing cell death. Thus, E2F-1, E2F-2, E2F
      3 and E2F-4 are able to overcome the p16-dependent proliferative block in U343
      astrocytoma cells. While overcoming this cell cycle block, each of the E2F's
      uniquely affect the expression of a number of cell cycle regulatory proteins and
      have distinct abilities to promote cell death.

PMID- 9780006
TI  - Reduced telomeric signals and increased telomeric associations in human lung
      cancer cell lines undergoing p53-mediated apoptosis.
AB  - Transduction of a p53-negative H1299 human non-small cell lung cancer cell line
      with an adenoviral vector containing wild-type p53 (Ad5p53) induced apoptosis.
      Analysis of the Ad5p53-infected H1299 cells showed high levels of telomeric
      association prior to apoptotic nuclear fragmentation. Similar telomeric
      association was observed in stably transfected clones of the wtH226b cell line,
      which expressed exogenous wild-type p53 protein and also showed complex
      chromosomal abnormalities including dicentrics, rings and fragments. Fluorescence
      in situ hybridization (FISH) analysis using a human telomeric DNA probe indicated
      reductions in telomere signals in both Ad5p53-infected H1299 cells and wtH226b-S
      cells. In contrast, stably transfected wtH226b-AS clones expressing antisense p53
      cDNA showed no telomeric association and had high levels of telomeric signals
      associated with a faster growing phenotype. These results suggest that wild-type
      p53 is involved in shortening telomeres, a possibly early event in the p53
      mediated apoptotic process and in the subsequent telomeric association that
      predisposes a cell to genetic instability and DNA fragmentation resulting in
      apoptotic cell death. Moreover, loss of telomeric signals may indicate a cell's
      decision to undergo programmed cell death and, if so, could, serve as a sensitive
      marker of p53-mediated apoptosis.

PMID- 9780005
TI  - Prolonged vs transient roles for early cell cycle signaling components.
AB  - Both p21ras and phosphatidylinositol 3-kinase (PI 3-k) are critical elements in
      signaling pathways mediating insulin/IGF-I induced cell cycle progression. For
      example, microinjection of antibodies, peptides, or recombinant proteins which
      block the interaction of the SH2 domains of the PI 3-k p85alpha subunit with
      tyrosine phosphorylated intracellular targets blocks insulin mediated DNA
      synthesis. We report here that this inhibitory phenotype is observed whether the
      injections are made into quiescent cells (the standard approach), or at any time
      point during G1 phase subsequent to stimulation. This observation is not true,
      however, for the major substrate of the insulin/IGF-I receptor (IRS-1) despite
      the well known interaction of p85 with IRS-1. Antibodies to IRS-1 are inhibitory
      only when injected during the first 15 min of G1 phase, as are antibodies to
      another major IRS-1 binding protein, the tyrosine phosphatase SHP2. We also have
      microinjected reagents which target proteins involved in the formation of rasGTP
      and which mediate some of the downstream effects of ras activation. Reagents
      which target the formation of rasGTP (Shc and dominant negative ras protein)
      inhibit DNA synthesis only at points early in G1, as do reagents which target
      components of the MAP kinase pathway. Injection of antibodies to p21ras itself,
      or a recombinant Raf-1 protein domain which binds to the effector region of ras
      in a GTP-dependent manner, results in the inhibition of cell cycle progression
      throughout G1 phase. The results point to a continuous requirement for both PI 3
      k and ras activity until cellular commitment to DNA synthesis, although some of
      the molecules which are both upstream and downstream of these activities are only
      required transiently. Our results are also consistent with a Raf-1 independent
      ras activity late in G1, as well as IRS-1 independent effects of PI 3-kinase.

PMID- 9780007
TI  - Malignant transformation of NIH3T3 cells by overexpression of mot-2 protein.
AB  - The murine mortalin genes, mot-1 and mot-2, are members of the hsp70 family of
      proteins and differ from each other by only two amino acid residues. Mot-1 is
      expressed in normal cells and has pancytosolic cellular distribution whereas mot
      2 is found in the perinuclear region of immortal cells. We report here that a
      high level of expression of mot-2 protein resulted in malignant transformation of
      cells as analysed by anchorage independent growth and nude mice assays. A high
      level of protein expression is attributed to the 900 bp 3' untranslated region of
      the cDNA which does not have any transforming activity per se. Mortalin cDNA
      clones isolated from human transformed cells were also found to have transforming
      activity in similar assays and a high level of expression was apparent in some of
      the human immortalized cells that showed non-pancytosolic mortalin
      immunofluorescence. Taken together, the data suggest that nonpancytosolic
      mortalin may have a role in tumorigenesis.

PMID- 9780008
TI  - Emodin (3-methyl-1,6,8-trihydroxyanthraquinone) inhibits TNF-induced NF-kappaB
      activation, IkappaB degradation, and expression of cell surface adhesion proteins
      in human vascular endothelial cells.
AB  - Most inflammatory agents activate nuclear transcription factor-kappaB (NF-kappaB)
      which results in expression of genes for cytokines, adhesion molecules, and
      enzymes involved in amplification and perpetuation of inflammation. Emodin (3
      methyl-1,6,8-trihydroxyanthraquinone) is an active component from the roots of
      Polygonum cuspidatum that has been reported to exhibit antiinflammatory
      properties but the mechanism is not known. In the present study we investigated
      the effects of emodin on the activation of NF-kappaB in human umbelical vein
      endothelial cells (EC). Treatment of EC with TNF activated NF-kappaB;
      preincubation with emodin inhibited this activation in a dose- and time-dependent
      manner. Emodin did not chemically modify NF-kappaB subunits but rather inhibited
      degradation of IkappaB, an inhibitory subunit of NF-kappaB. Since the promoter
      regions of ICAM-1, VCAM-1, and ELAM-1 contain NF-kappaB binding sites and these
      adhesion molecules are involved in the attachment of leukocytes to EC, the effect
      of emodin on the adhesion of monocytes to EC and the expression of these adhesion
      molecules was also studied. Treatment of EC with TNF for 6 h increased the
      adhesion of monocytes to EC, which correlated with increases in cell surface
      expression of ICAM-1, VCAM-1 and ELAM-1. Pretreatment of EC for 1 h with emodin
      inhibited both monocyte-EC attachment and expression of ICAM-1, ELAM-1 and VCAM
      1. These results indicate that emodin is a potent inhibitor of NF-kappaB
      activation and expression of adhesion molecules and thus could be useful in
      treating various inflammatory diseases.

PMID- 9780009
TI  - Two erbB-4 transcripts are expressed in normal breast and in most breast cancers.
AB  - ErbB-4 is a recently described member of the epidermal growth factor receptor
      (EGFR) family which together with erbB-3 acts as a receptor for a group of
      ligands known as the neuregulins (NRGs) or heregulins (HRGs). Unlike the EGFR and
      erbB-2 relatively little is known about the expression of erbB-4 in human
      tumours. Using RT-PCR and Southern blotting analysis we have investigated the
      expression of erbB-4 mRNA in a range of human tumour cell lines and in normal and
      malignant breast tissue. Using primers which amplified a 658 base pair (bp)
      region corresponding to part of the cytoplasmic domain of c-erbB-4 we found the
      receptor was expressed in some but not all breast and ovarian tumour cell lines
      and also in a glioma cell line. The highest level of erbB-4 expression was found
      in the ovarian carcinoma OVCAR-3 and the breast carcinoma T-47D. In all cell
      lines where the 'full-length' erbB-4 was detected, a second previously
      undescribed c-erbB-4 sequence was also found as a 610 bp PCR product. The
      alternative PCR product was identical in sequence to c-erbB-4 except for a
      deletion of 48 bp which encodes a consensus phosphatidylinositol 3-kinase (PI3K)
      binding site. This suggested that the two forms of erbB-4 might interact with
      different intracellular signalling pathways and therefore influence a wider
      variety of cellular responses to heregulin than previously thought. Expression of
      both erbB-4 variants was found in 7/7 normal breast tissues but only in 9/12
      breast tumours analysed. In line with the terminology of Elenius et al. (1997b)
      we have designated the two isoforms of the C-terminal transcripts as CT-a (full
      length) and CT-b which lacks the P13K binding motif. These results identify
      suitable cell lines for the further investigation of erbB-4 expression and
      function and suggest that the role of erbB-4 in breast cancer warrants further
      investigation with larger numbers of normal and malignant breast tissues.

PMID- 9780010
TI  - A new candidate site for a tumor suppressor gene involved in mouse thymic
      lymphomagenesis is located on the distal part of chromosome 4.
AB  - In a previous work we provided preliminary evidence of the existence of a
      putative tumor suppressor gene region on the distal part of chromosome 4 in gamma
      radiation-induced T-cell lymphomas of (C57BL/6J x RF/J) F1 hybrid mice. This
      region, named as TLSR2 (Thymic Lymphoma Suppressor Region 2), was located
      centered at D4Mit54. A more detailed allelotype analysis in the mentioned tumors
      with new informative microsatellites on distal chromosome 4 region, as well as in
      thymic lymphomas induced with gamma-rays in F1 hybrids generated from reciprocal
      crosses between the strains C57BL/6J and BALB/cJ, and having in mind the new map
      position of D4Mit205b, allowed us to confirm the existence of TLSR2 and to define
      it more precisely as centered at D4Mit205b. In addition, we identified a new
      candidate region, named as TLSR3 (Thymic Lymphoma Suppressor Region 3), located
      between the Mom-1 locus and D4Mit68, as the site of another putative tumor
      suppressor region involved in thymic lymphomagenesis.

PMID- 9780011
TI  - Dermatomal and mixed nerve somatosensory evoked potentials in the diagnosis of
      neurogenic thoracic outlet syndrome.
AB  - To evaluate the diagnostic utility of dermatomal and mixed nerve somatosensory
      evoked potentials (SEPs) in patients with thoracic outlet syndrome (TOS) and to
      compare their value with routine electrodiagnostic methods, we studied a group of
      44 patients with neurogenic TOS and 30 healthy controls. In addition to bilateral
      median and ulnar SEPs, evoked potentials were recorded after stimulation of C6
      and C8 dermatomes from the first and fifth digits, respectively. The patients
      were classified into 3 groups according to the nature of their clinical
      condition. The abnormality rate for both ulnar and C8 dermatomal SEPs was 100% in
      a small group of patients with severe neurological signs like atrophy. In groups
      of patients with lesser degrees of neurogenic damage, abnormality rates for ulnar
      and C8 dermatomal SEPs on affected limb(s) were 67 and 50%, respectively. Same
      abnormality rates were 25 and 18% in patients with only subjective symptoms. In
      patients with objective neurological signs, the major increase in sensitivity was
      with electromyography (EMG). Abnormalities of routine nerve conduction studies
      and F-wave latency were observed in patients with severe neurogenic damage. We
      concluded that the most useful tests in the diagnosis of neurogenic TOS are
      needle EMG and ulnar SEPs.

PMID- 9780012
TI  - The covert interplay between perception and memory: event-related potential
      evidence.
AB  - Neurocognitive models of visual object identification have focussed on processes
      at the moment of identification, when perceivers can actually name what they see.
      Less well known is the timecourse of processes preceding and leading to actual
      identification. To track neuromental processes involved in visual identification,
      behavioral measures and event-related potentials (ERPs) were recorded in two
      experiments prior to, during and after the identification of fragmented objects,
      half of which had been shown in their complete versions in a previous study
      phase. Each object was revealed in a sequence of frames wherein the object was
      represented by an increasingly less and less fragmented image up to the complete
      version. A shift in ERPs, around 300 ms and beyond, from negativity to
      positivity, marked the transition from non-identification to identification.
      However, while for new stimuli such a shift appeared abruptly from non
      identification to identification, for recently-studied objects a late positive
      wave emerged in response to unidentified fragments at a level just prior to overt
      identification. Thus, ERPs reflected covert processes associated with a
      successful match between the current visual information and episodic recently
      stored memory traces, which predicted overt identification.

PMID- 9780013
TI  - The N18 component of the median nerve SEP is not reduced by vibration.
AB  - OBJECTIVE: To study the interference of mechanical vibration of the palm of the
      hand on the median nerve short-latency SEP components. METHODS: Electrically
      elicited short-latency median nerve SEP were obtained before and during
      mechanical vibration (120 Hz) of the palm in two groups of normal individuals (6
      in group I and 9 in group II). The amplitude of the different components was
      compared between the two conditions through non-parametric statistical tests.
      RESULTS: A significant reduction in the amplitude of the N9, P13/14 and N20
      components was detected, however no overall significant changes were detected for
      the N18 component. CONCLUSIONS: Vibration interference reduced all studied
      components except the N18, these findings are interpreted as supporting evidence
      for the proposed association between the N18 component and the inhibitory
      activities elicited in the dorsal column nuclei.

PMID- 9780014
TI  - Magnetic stimulation of the corticospinal tracts in Pelizaeus-Merzbacher disease.
AB  - To evaluate conduction abnormalities of the corticospinal tracts (CSTs) in
      Pelizaeus-Merzbacher disease (PMD), magnetic stimulation at three levels was
      carried out in 3 boys with PMD aged between 9 and 12 years. They were all
      diagnosed as having a duplicated proteolipid protein gene. The motor cortex and
      cervical spinal roots were stimulated with a round coil, whereas a double cone
      coil was used for brain-stem stimulation. Surface electromyographic (EMG)
      recording was performed on the first dorsal interosseous muscles. Despite a
      normal EMG response to cervical stimulation, magnetic shock of the motor cortex
      elicited no EMG activity, even in the case with less motor symptoms. This
      discrepancy between the electrophysiological and clinical findings is likely due
      to slowing conduction, which reduces the temporal summation of multiple
      descending volleys magnetically elicited. A partial conduction block may also
      occur because of the lack of an EMG response to brain-stem stimulation. Thus, we
      speculated that the spastic paresis in PMD is associated with both slowing
      conduction and a partial conduction block in the CSTs.

PMID- 9780015
TI  - Relation of olfactory event-related potentials to changes in stimulus
      concentration.
AB  - OBJECTIVE: The aim of this study was to investigate the influence of odorant
      concentration on the olfactory event-related potential (OERP). METHODS: OERP were
      evaluated in 8 men and 8 women (17-34 years of age) in response to 4
      concentrations of vanillin (7, 28, 56 and 84% v/v). Sixteen presentations of each
      concentration (stimulus duration 200 ms, interval 40 s, flow 81/min) were applied
      in a randomized order. EEG recordings were made at 3 midline sites (pos. Fz, Cz,
      Pz). Amplitudes and latencies of four peaks were measured (latencies in ms at Pz
      after stimulation with 84% v/v vanillin): P1 (277), N1 (348), P2 (412) and P3
      (496). Statistical analysis was performed with MANOVAs ('concentration',
      'recording site' = within-subject-factors; 'age' as covariate). RESULTS: With
      increasing stimulus concentration amplitudes became significantly larger; this
      was most pronounced for P3 (P1N1: F = 2.90, P < 0.05; N1P2: F = 5.15, P < 0.01;
      N1P3: F = 35.7, P < 0.001; P3: F = 38.6; P < 0.001). Correspondingly, latencies
      shortened with increasing concentrations (P1: F = 25.2; N1: 17.51; P2: 14.8; P3:
      13.4; all P < 0.001). While there was no correlation between OERP amplitudes and
      butanol odor detection thresholds, latencies were the shorter the lower the
      subjects' thresholds (coefficients of correlations for peak latencies at Cz for
      84% v/v: P1 rl5 = -0.59; N1 rl5 = 0.58; P2 r15 = -0.55; P3 r15 = -0.45).
      CONCLUSIONS: The results indicated that both OERP amplitudes and latencies are
      related to the concentration of olfactory stimuli. They also suggested that
      latencies exhibit a stronger relation to changes in stimulus intensity compared
      to OERP amplitudes.

PMID- 9780016
TI  - The N400 in a semantic categorization task across 6 decades.
AB  - OBJECTIVES: To characterize the effects of normal aging on the amplitude, latency
      and scalp distribution of the N400 congruity effect. METHODS: Event-related brain
      potentials (ERPs) were recorded from 72 adults (half of them men) between the
      ages of 20 and 80 years (12/decade) as they performed a semantic categorization
      task. Participants listened to spoken phrases (e.g. 'a type of fruit' or 'the
      opposite of black') followed about 1 s later by a visually-presented word that
      either did or did not fit with the sense of the preceding phrase; they reported
      the word read and whether or not it was appropriate. ERP measurements (mean
      amplitudes, peak amplitudes, peak latencies) were subjected to analysis of
      variance and linear regression analyses. RESULTS: All participants, regardless of
      age, produced larger N400s to words that did not fit than to those that did. The
      N400 congruity effect (no-fit ERPs - fit ERPs) showed a reliable linear decrease
      in the amplitude (0.05-0.09 microV per year, r = 0.40) and a reliable linear
      increase peak latency (1.5-2.1 ms/year, r = 0.60) with age. CONCLUSIONS: In sum,
      the N400 semantic congruity effect at the scalp gets smaller, slower and more
      variable with age, consistent with a quantitative rather than qualitative change
      in semantic processing (integration) with normal aging.

PMID- 9780017
TI  - Visual cognitive dysfunction in depression: an event-related potential study.
AB  - The P3(00) event-related potentials (ERPs) elicited by visual stimuli in two
      visual tasks were assessed in depressed patients (12 patients with major
      depression and 11 patients with bipolar disorder) and compared with those of 20
      age-matched normal controls. At remission, the ERPs from 18 of the depressed
      patients were again recorded. The visual oddball (VO) paradigm presented both
      target and standard visual stimuli and the simple visual (SV) paradigm presented
      a target but no standard visual stimulus. Subjects performed the VO task
      significantly less accurately than the SV task, as reflected by the behavioral
      measures (reaction-time and task accuracy). Depressed patients of the bipolar
      group showed longer P3 peak latency for the VO task and no change in P3
      amplitude. No significant differences were found in any other ERP component
      between the groups. During remission, slowing RTs and reduced P3 peak latencies
      were observed for both major depression and bipolar disorder groups. Thus, the P3
      ERP may be an index of the contribution of the slowed central processing to
      psychomotor retardation in clinically homogenous samples of depressive patients
      performing an appropriately demanding task.

PMID- 9780019
TI  - Neural conduction in visual pathways in newly-diagnosed IDDM patients.
AB  - OBJECTIVES: Visual evoked potentials (VEPs) show abnormal responses in newly
      diagnosed insulin-dependent diabetic (IDDM) patients. Electrophysiological
      methods allow one to dissect and explore different structures contributing to
      neural conduction in the visual pathways. The aim of our work was to assess
      whether the VEP abnormalities are due to impaired function of the retinal layers
      and/or a delayed conduction in the postretinal visual pathways. METHODS:
      Simultaneous recordings of VEP and pattern-electroretinogram (PERG) were
      performed at two intervals (at entry of the study and after 3 months) in 14 newly
      diagnosed IDDM patients (age: 24.8+/-6.8 years; duration of disease: 3+/-1.5
      months), and in 14 age-matched control subjects. RESULTS: In comparison with
      control subjects, IDDM patients showed: VEP P100 latencies significantly delayed
      (P < 0.01), a significant impairment of all PERG parameters (P < 0.01) and
      retinocortical time (RCT, difference between VEP P100 and PERG P50 latencies) and
      latency window (LW, difference between VEP N75 and PERG P50 latencies) also
      significantly increased (P < 0.01). All electrophysiological parameters were not
      significantly changed when retested after 3 months. No correlations were found
      between VEP P100 latency, RCT, LW and PERG parameters. CONCLUSIONS: Impaired PERG
      indicates an involvement of the innermost retinal layers; increased values of RCT
      and LW represent an index of delayed neural conduction in the postretinal visual
      pathways. Therefore two sources, one retinal (impaired PERG) and one postretinal
      (delayed RCT and LW), may independently contribute in to the abnormal responses
      of VEP observed in newly-diagnosed IDDM patients. Three months of relatively
      stable metabolic control have not normalized the VEP and PERG impairment.

PMID- 9780018
TI  - Sympathetic skin responses recorded from non-palmar and non-plantar skin sites:
      their role in the evaluation of thermal sweating.
AB  - OBJECTIVE: To characterize the sympathetic skin responses (SSRs) recorded from
      non-palmar and non-plantar (non-Pa/P1) skin sites and to evaluate their clinical
      usefulness. METHODS: SSRs were recorded from 6 non-Pa/P1 sites as well as palmar
      and plantar (Pa/P1) sites using magnetic neck stimulation in 33 normal subjects,
      17 neurological patients with dysautonomia and one patient with lumbar
      sympathectomy. A conventional thermoregulatory sweat test (TST) was also carried
      out in 3 patients. RESULTS: Clear and reproducible SSRs were obtained from all
      recording sites in all of the normal subjects when the skin temperatures of the
      subjects were maintained above 34 degrees C and the subjects drank 100-200 ml of
      hot water. The distribution of absent SSRs was closely correlated with that of
      anhidrosis or a sweating delay shown by the TST in the patients. Nine of the 17
      neurological patients (53%) showed normal responses at Pa/P1 sites, and abnormal
      responses at non-Pa/P1 sites. CONCLUSIONS: Recording SSRs from multiple skin
      sites including non-Pa/P1 sites after magnetic stimulation is more sensitive in
      detecting sudomotor dysfunction than is the conventional method of recording SSRs
      from only Pa/P1 sites. In addition, this new method is very useful for the
      objective clinical evaluation of thermal sweating.

PMID- 9780020
TI  - EEG theta and frontal alpha oscillations during auditory processing change with
      aging.
AB  - The present study assessed the effect of age on time and frequency components of
      auditory evoked potentials in two groups of adults, young (18-30 years old) and
      middle-aged (50-55 years old). Averaged and single-sweep potentials were
      analyzed. Analysis of single alpha and theta responses was performed for 3
      parameters - single-sweep amplitude, phase-locking, and enhancement. Significant
      age differences were revealed only at the level of single sweeps: (i) at the 3
      mid-line locations (Fz, Cz, and Pz), middle-aged adults manifested theta phase
      locking and enhancement which were significantly stronger than those in young
      adults; and (ii) in contrast, only over the frontal brain area were the alpha
      responses stronger in phase-locking and enhancement in the middle-aged than in
      young subjects. Thus, the analysis of frequency responses at the level of single
      sweeps enabled us to reveal age differences in simple auditory stimulus
      processing that were otherwise not detectable in the averaged potential. The
      results imply that the alpha response system may relate to frontal brain
      functioning during aging.

PMID- 9780021
TI  - Spike-induced interference in auditory sensory processing in Landau-Kleffner
      syndrome.
AB  - OBJECTIVES: Landau-Kleffner Syndrome (LKS) is an epileptic syndrome characterised
      by a deficit in language comprehension and production, paroxysmal epileptiform
      activity in the posterior temporal leads, and by the inconsistent presence of
      epileptic fits. Its interest lies in the fact that it stands as a model for the
      study of interference of epileptiform activity on cognitive function, although
      the pathophysiology of the decline in language skills that follows its onset has
      not yet been clarified. METHODS: We have recorded spike-triggered auditory evoked
      responses in a group of 6 children with LKS, to investigate whether the
      occurrence of individual EEG paroxysms is able per se to induce a decline in the
      response of the auditory cortex. RESULTS: Results have indicated that left
      hemisphere spikes are associated with a greater reduction in amplitude and an
      increase in latency of the NI, than spikes occurring in the right hemisphere. No
      stable change in the evoked response has been detected outside of the EEG
      paroxysm. CONCLUSIONS: We postulate EEG interictal activity is able to induce
      impairment in processing auditory information and that this may play a role in
      the pathogenesis of language deficit in LKS.

PMID- 9780022
TI  - Effects of localized pontine lesions on auditory brain-stem evoked potentials and
      binaural processing in humans.
AB  - OBJECTIVES AND METHODS: Four sets of measurements were obtained from 11 patients
      (44-80 years old) with small, localized pontine lesions due to vascular disease:
      (1) Monaural auditory brain-stem evoked potentials (ABEPs; peaks I to VI); (2)
      Binaural ABEPs processed for their binaural interaction components (BICs) in the
      latency range of peaks IV to VI; (3) magnetic resonance imaging (MRI) of the
      brain-stem; and (4) psychoacoustics of interaural time disparity measures of
      binaural localization. ABEPs and BICs were analyzed for peak latencies and
      interpeak latency differences. Three-channel Lissajous' trajectories (3-CLTs)
      were derived for ABEPs and BICs and the latencies and orientations of the
      equivalent dipoles of ABEP and BICs were inferred from them. RESULTS:
      Intercomponent latency measures of monaurally evoked ABEPs were abnormal in only
      3 of the 11 patients. Consistent correlations between sites of lesion and
      neurophysiological abnormality were obtained in 9 of the 11 patients using 3-CLT
      measures of BICs. Six of the 11 patients had absence of one or more BIC
      components. Seven of the 11 had BICs orientation abnormality and 3 had latency
      abnormalities. Trapezoid body (TB) lesions (6 patients) were associated with an
      absent (two patients with ventral-caudal lesions) or abnormal (one patient with
      ventral-rostral lesions) dipole orientation of the first component (at the time
      of ABEPs IV), and sparing of this component with midline ventral TB lesions (two
      patients). A deviant orientation of the second BICs component (at the time of
      ABEPs V) was observed with ventral TB lesions. Psychoacoustic lateralization in
      these patients was biased toward the center. Rostral lateral lemniscus (LL)
      lesions (3 patients) were associated with absent (one patient) or abnormal (two
      patients) orientation of the third BICs component (at the time of ABEPs VI); and
      a side-biased lateralization with behavioral testing. CONCLUSIONS: These results
      indicate that: (1) the BICs component occurring at the time of ABEPs peak IV is
      dependent on ventral-caudal TB integrity; (2) the ventral TB contributes to the
      BICs component at the time of ABEPs peak V; and (3) the rostral LL is a
      contributing generator of the BICs component occurring at the time of ABEP peak
      VI.

PMID- 9780023
TI  - Solubilization and pharmacological characterization of a glucocorticoid membrane
      receptor from an amphibian brain.
AB  - Physiological functions of steroid hormones involve activation of intracellular
      receptors as well as poorly understood membrane receptors. We report the
      pharmacological characterization of a solubilized corticosterone receptor from
      neuronal membranes. This receptor previously was shown to localize with plasma
      membrane subcellular fractions and to be involved in the modulation of courtship
      behaviors in the roughskin newt (Taricha granulosa). We describe procedures with
      non-ionic detergents that solubilize the receptor and maintain high affinity
      [3H]corticosterone binding. The pharmacology of the solubilized corticosterone
      receptor resembles that of the membrane receptor with high affinity for
      [3H]corticosterone and an identical rank-order potency for other steroid ligands
      (corticosterone>cortisol>aldosterone>dexamethasone). Unlike binding in membrane
      preparations, [3H]corticosterone binding to the solubilized receptor is
      insensitive to negative modulation by guanyl nucleotides and only modestly
      sensitive to the presence of Mg2+. We also identified two ligands that exhibit
      high affinity binding to the solubilized receptor and have the potential to be
      used in an affinity purification scheme. They are corticosterone-3
      carboxymethyloxime (CORT-3-CMO), which may be covalently attached to a Sepharose
      resin, and a derivitized azide form of CORT-3-CMO which can be covalently coupled
      to the solubilized receptor itself. The stability of the solubilized
      [3H]corticosterone receptor in the detergent system will facilitate further
      purification and molecular characterization.

PMID- 9780024
TI  - Expression of exon 5 deleted estrogen receptor variant messenger RNA in human
      uterine myometrium and leiomyoma.
AB  - To examine the relationship between uterine leiomyoma, an estrogen-dependent
      tumor and its estrogen receptor, the relative amounts of wild type estrogen
      receptor (WT) mRNA and exon 5 deleted estrogen receptor variant (D5-ER) mRNA to
      G3PDH mRNA were examined in human uterine myometrium and leiomyoma specimens
      obtained from 46 patients in 3 age groups (group A: 41-45 years old, group B: 46
      50 years old, group C: 51-54 years old) using a quantitative reverse
      transcription polymerase chain reaction method (RT-PCR). D5-ER mRNA was co
      expressed with WT mRNA in all myometrium and leiomyoma specimens. In myometrium,
      the relative amount of WT decreased with aging, but in leiomyoma, it was high in
      group B. The relative amount of D5-ER mRNA and the ratio of D5-ER mRNA to WT mRNA
      (D5/WT ratio) were significantly higher in group C in both myometrium and
      leiomyoma. The percentage of the patients whose D5/WT ratio was higher in
      leiomyoma than in myometrium (L/M ratio>1.0) increased with age. These findings
      suggest that D5-ER increases to supplement the decreasine in WT in uterine
      tissues toward menopause and that D5-ER plays a more active role in leiomyoma
      than in myometrium during the perimenopausal period.

PMID- 9780025
TI  - Transcriptional suppression of estrogen receptor gene expression by 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD).
AB  - TCDD, the most potent congener of the polychlorinated dioxins, has been shown to
      be an antiestrogen. The mechanisms of TCDD-induced antiestrogenicity are still
      under investigation. In this study, we investigated the effects of TCDD on the
      expression of the estrogen receptor (ER) gene. We studied the levels of un
      spliced ER transcript (hnRNA) as well as the ER mRNA in ovary, uterus and liver
      of TCDD-treated mice with different genetic backgrounds. To quantitate the ER
      hnRNA levels, the intron and exon boundary of ER hnRNA was amplified by
      competitive RT-PCR. The ER mRNA from these mice was quantitated by competitive RT
      PCR amplifying exons separated by an intron. ER hnRNA and ER mRNA levels were
      quantitated 4 days after a single i.p. dose of TCDD (5 microg/kg) in female
      C57BL/6J (B6) mice, which carry the responsive allele to TCDD. TCDD treatment
      significantly (p < 0.05) suppressed the levels of ER hnRNA in the ovary (27.4%)
      and uterus (21.9%). The decreases in ER hnRNA were coordinated with significant
      (p < 0.01) decreases in ER mRNA in ovary (57.7%) and uterus (37.6%). There was a
      significant decrease (20.3%, p < 0.05) in liver ER mRNA, however, the changes of
      ER hnRNA in liver were not significant. The coordinated decreases in ER hnRNA and
      mRNA in TCDD-treated mice suggest a suppression of transcription of the ER gene.
      We performed the same study on DBA/2J (D2) mice, which possess the "non
      responsive" allele of the aryl hydrocarbon receptor (AhR). These mice
      demonstrated no significant decrease in either the ER mRNA or hnRNA after TCDD
      treatment. Overall, these results suggest that TCDD suppresses the gene
      expression of the ER receptor by decreasing its transcription, and the AhR plays
      an important role in mediating this response.

PMID- 9780026
TI  - Sex steroidal regulation of vessel permeability associated with vessel
      endothelial cadherin (V-cadherin).
AB  - In an attempt to understand the roles of cadherins in the placenta, mRNA
      expression and biological function of cadherins in 3A(tPA-30-1) cells (derived
      from human term placenta and transformed by SV40), and in HUV-EC-C cells (derived
      from the endothelial cells in human umbilical cord) were studied under the
      influence of sex steroids. Estradiol transiently decreased the endothelial cell
      barrier properties (ECBP) of HUV-EC-C cells, and progesterone reversed the
      changes induced by estradiol. However, neither estradiol nor progesterone
      demonstrated any effect on cell aggregation of either 3A(tPA-30-1) or HUV-EC-C
      cells. Estradiol transiently decreased the level of V-cadherin and its mRNA in
      HUV-EC-C cells, and progesterone reversed the level decreased by estradiol.
      However, neither estradiol nor progesterone demonstrated any effect on the level
      of E-cadherin mRNA in 3A(tPA-30-1) cells. Therefore, a sex steroidal role for
      placental development and function related to cadherins seems to focus on the
      endothelial cells, plausibly via vessel permeability for the utilization of
      placental products.

PMID- 9780028
TI  - 6-Phenylaliphatic-substituted androst-4-ene-3,17-diones as aromatase inhibitors:
      structure-activity relationships.
AB  - Two series of 6alpha- and 6beta-phenylaliphatic-substituted androst-4-ene-3,17
      diones (3 and 5) were synthesized as aromatase inhibitors to gain insights of
      structure-activity relationships of varying the n-alkyl moiety (C2 to C5) of the
      6-phenylaliphatic substituents to the inhibitory activity. All of the inhibitors
      synthesized inhibited human placental aromatase in a competitive manner with
      apparent Ki values ranging from 16 to 115 nM. The 6alpha-phenethyl analog 3a and
      the 6beta-phenbutyl analog 5c (Ki=16 nM for the two inhibitors, respectively)
      were the most potent inhibitors in each series. The inhibitory activities of the
      6beta-substituted steroids 5 except for the phenethyl compound 5a were more
      powerful than those of the corresponding 6alpha-isomers 3. Elongation of the
      alkyl moiety of the 6-substituent of the 6alpha-phenethyl steroid 3a up to five
      methylene units decreased affinity to aromatase in all cases, whereas the
      addition of two more methylene units to the 6-side chain of the 6beta-phenethyl
      analog 5a increased the affinity in relation to carbon number of the 6
      substituent. These results along with molecular modelling with the PM3 method,
      would give a new information about the formation of thermodynamically stable
      enzyme-inhibitor complex in a hydrophobic binding pocket in the active site of
      aromatase.

PMID- 9780027
TI  - Transfer of [3H]estrone-[35S]sulfate across guinea pig fetal membranes.
AB  - The possible role of fetal membrane deconjugating activity in the movement of a
      charged steroid conjugate between fetal and maternal compartments was
      investigated. The ability of amnion and chorion laeve to transfer [3H]estrone
      [35S]sulfate was assessed in both orientations of guinea pig tissue at 45 days
      and near parturition. While early amnion was impermeable, late tissue transferred
      approximately 50% (w/w) of the substrate in a bidirectional process that was non
      saturable and independent of either deconjugation or ATP. Transfer across early
      chorion was similar to late amnion. Saturation curves from each tissue were
      superimposable, as were those of the time course. Transfer across both early and
      late chorion proceeded in the absence of deconjugation, with no effect of tissue
      orientation or ATP depletion. However, late chorion exhibited a decrease in
      estrone-sulfate transfer, as verified by concentration dependency and time course
      analyses, though transport across the tissue remained non-saturable. The results
      in amnion were congruous with the presence and absence of tight junctions in the
      epithelium of early and late tissue, respectively. However, sulfoconjugate
      transfer across early chorion proceeded in the presence of a paracellular
      barrier, suggesting specialized regulation of the transport process which
      extended late into gestation.

PMID- 9780029
TI  - In vitro inhibition of androstenedione 5alpha-reduction by finasteride in
      epithelium and stroma of human benign prostatic hyperplasia.
AB  - Finasteride is a well known steroid 5alpha-reductase inhibitor. In this context,
      recently we have shown that in human benign prostatic hyperplasia (BPH)
      finasteride inhibits the 5alpha-reduction of testosterone to dihydrostestosterone
      (DHT) more effectively in the epithelium as compared to the stroma. The aim of
      the present study was to describe in epithelium and stroma of human BPH the
      effect of finasteride on the 5alpha-reduction of androstenedione, that is the
      second main circulating androgen in men, to androstanedione. Using a finasteride
      concentration of 75 nM and an androstenedione concentration of 220 nM, the mean
      inhibition [% +/- SEM] of 5alpha-reductase activity was significantly higher in
      epithelium (69 +/- 2) than in stroma (52 +/- 4). Both in epithelium and stroma,
      this inhibition of 5alpha-reductase activity was dose-dependent and competitive.
      Dixon plots as well as slope replots of Lineweaver-Burk plots showed that the
      mean inhibition constant Ki (nM +/- SEM) was significantly lower in epithelium
      (10 +/- 1 and 11 +/- 2, respectively) than in stroma (33 +/- 7 and 28 +/- 4,
      respectively) indicating a significantly stronger inhibitory effect of
      finasteride in epithelium. From those mean Ki values, it follows that in human
      BPH finasteride inhibits equally well both the 5alpha-reduction of
      androstenedione to androstanedione and testosterone to DHT. Based on these
      inhibition studies, there is no evidence for the coexistence of substrate
      specific 5alpha-reductases converting either testosterone or androstenedione.
      However, the striking difference in finasteride sensitivity of the 5alpha
      reduction between epithelium and stroma could be due to a cell-type specific
      expression of structurally different 5alpha-reductases as well as to a different
      access of finasteride to 5alpha-reductase in epithelium and stroma where,
      compared to each other, the lipid environment is significantly different.

PMID- 9780031
TI  - Biotransformation XLV. Transformations of 4-ene-3-oxo steroids in Fusarium
      culmorum culture.
AB  - The course of transformations of five 4-ene-3-oxo steroids with varying
      substituents at C-17 i.e.: 4-androsten-3-one, androstenedione, testosterone,
      progesterone and 17alpha-hydroxyprogesterone in Fusarium culmorum culture was
      investigated. All the substrates were hydroxylated either at 12beta and 15alpha,
      or at 15alpha or 6beta positions, depending on the structure of the substrate.
      The main product of 4-androsten-3-one transformation was 12beta,15alpha-diol. A
      similar 12beta,15alpha-diol was obtained from progesterone, but the main product
      of transformation of this substrate was 15alpha-hydroxyprogesterone. The products
      of hydroxylation at 6beta or 15alpha positions were isolated from 17alpha
      hydroxyprogesterone. The androstenedione and testosterone transformation mixtures
      contained the same products (6beta-hydroxyandrostenedione, 6beta
      hydroxytestosterone, 15alpha-hydroxyandrostenedione and 15alpha
      hydroxytestosterone), but the quantities of 6beta- and 15alpha-alcohols varied,
      depending on the substrate used. During transformations of these two substrates,
      apart from hydroxylation, ketone-alcohol interconversion at C-17 occurred.

PMID- 9780030
TI  - Effect of estrogens on the oxidative damage induced by ferrylmyoglobin.
AB  - The effect of estrogens, including estrone (E1), estradiol-17beta (E2), estriol
      (E3) and 2-hydroxyestradiol (2-OH-E2), on the oxidative damage induced by
      ferrylmyoglobin (ferrylMb) was investigated. These estrogens inhibited lipid
      peroxidation induced by ferrylMb. The ability of 2-OH-E2 to inhibit lipid
      peroxidation was much greater than the other estrogens. Furthermore, 2-OH-E2
      trapped 2,2'-azobis-(2-amidinopropane)-dihydrochloride peroxyl radicals more
      rapidly, and among these estrogens only 2-OH-E2 reacted with 2,2-diphenyl-1
      picrylhydrazyl. These results suggest that the ability of 2-OH-E2 to inhibit
      lipid peroxidation is because it scavenges lipid peroxyl and carbon-centered
      radicals. Estrogens, except for 2-OH-E2, partially prevented the inactivation of
      alcohol dehydrogenase (ADH) induced by ferrylMb. Of interest, however, the
      exposure of sulfhydryl (SH) enzymes to ferrylMb in the presence of 2-OH-E2
      dramatically increased the inhibition of the enzyme activity. Ascorbic acid (ASA)
      and reduced glutathione (GSH) strongly inhibited the inactivation of ADH induced
      by ferrylMb in the presence of 2-OH-E2. During the reaction of ferrylMb with ASA
      or GSH in the presence of 2-OH-E2, large amounts of oxymyoglobin were formed,
      suggesting the involvement of the semiquinone from 2-OH-E2 in the reduction of
      metmyoglobin. Presumably, the semiquinone formed from 2-OH-E2 oxidizes the SH
      group of enzymes to facilitate the rapid inactivation of the SH enzymes induced
      by ferrylMb.

PMID- 9780032
TI  - Cell differentiating and anti-proliferative activity of side-chain modified
      analogues of 1,25-dihydroxyvitamin D3.
AB  - Besides its calcium mobilizing activity in vivo, 1,25-dihydroxyvitamin D3 has the
      ability to induce differentiation of human promyelocytic leukemia cells in vitro.
      We studied the cell differentiating activity of four novel analogues of 1,25
      dihydroxyvitamin D3, using the HL60 cell line as a model. We also analyzed the
      influence of these compounds on the proliferation of HL60 cells, normal human
      keratinocytes, normal fibroblasts from human skin and human keratinocytes
      transfected with human papillomavirus type 16. Two of the four analogues, i.e.
      those with extended side-chain, were found to display similar cell
      differentiating and anti-proliferative activities as 1,25-dihydroxyvitamin D3.
      The other two analogues, with a shortened side-chain which included an additional
      hydroxyl, showed a substantially lower activity than that of 1,25
      dihydroxyvitamin D3. We observed distinct differences in sensitivity to the anti
      proliferative activity of either 1,25-dihydroxyvitamin D3 or its analogues
      between cells of different origin.

PMID- 9780033
TI  - Promoter activity associated with the intergenic regions of banana bunchy top
      virus DNA-1 to -6 in transgenic tobacco and banana cells.
AB  - Promoter regions associated with each of the six ssDNA components of banana
      bunchy top virus (BBTV) have been characterized. DNA segments incorporating the
      intergenic regions of BBTV DNA-1 to -6 were isolated and fused to the uidA (beta
      glucuronidase) reporter gene to assess promoter activity. In tobacco cell
      suspensions, the BBTV DNA-2 and -6 promoters generated levels of GUS expression 2
      fold greater and similar to the 800 bp CaMV 35S promoter, respectively. Deletion
      analysis of the BBTV DNA-6 promoter suggested all the necessary promoter elements
      required for strong expression were located within 239 nucleotides upstream of
      the translational start codon. In transgenic tobacco plants, the BBTV-derived
      promoters generally provided a weak, tissue-specific GUS expression pattern
      restricted to phloem-associated cells. However, in callus derived from tobacco
      leaf tissue, GUS expression directed by the BBTV DNA-6 promoter was strong and,
      in some lines, comparable to the CaMV 35S promoter. Detectable promoter activity
      associated with the BBTV promoters in banana embryogenic cells was only observed
      using a sensitive green fluorescent protein (GFP) reporter. Promoters derived
      from BBTV DNA-4 and -5 generated the highest levels of transient activity, which
      were greater than that of the maize ubi-1 promoter. In transgenic banana plants,
      the activity of the BBTV DNA-6 promoter was restricted to the phloem of leaves
      and roots, stomata and root meristems.

PMID- 9780034
TI  - Molecular characterization of a new whitefly-transmissible bipartite geminivirus
      infecting tomato in Panama.
AB  - The nucleotide sequence of infectious clones of a tomato-infecting geminivirus
      from Panama [named tomato leaf curl virus (ToLCV-Pan) because of symptoms
      produced in infected tomato (plant stunting and mild leaf curling)] was
      determined. ToLCV-Pan has a bipartite genome (DNAs A and B) and computer analysis
      showed that the genome resembles that of other bipartite, whitefly-transmitted
      geminiviruses. DNA A (2584 nt) and B (2542 nt) have little sequence homology
      other than within the common region. ToLCV-Pan clones were introduced into
      Lycopersicon esculentum and infected plants developed the same symptoms as
      naturally infected tomatoes. Homology analysis of DNA A and B showed that ToLCV
      Pan is most closely related to potato yellow mosaic virus (PYMV) from Venezuela.
      Pseudorecombination between ToLCV-Pan and PYMV did not give viable
      pseudorecombinant viruses. However, in some plants infected with the
      pseudorecombinant virus produced by ToLCV-Pan DNA A and PYMV DNA B, systemic
      movement of ToLCV-Pan DNA A was observed.

PMID- 9780035
TI  - Localization of the P1 protein of potato Y potyvirus in association with
      cytoplasmic inclusion bodies and in the cytoplasm of infected cells.
AB  - The N-terminal P1 proteinase of potato virus Y (ordinary strain group isolate PVY
      O) was expressed in E. coli. Antiserum was raised against the expressed protein
      and used to detect the viral proteins in infected tobacco leaf tissue by Western
      blotting and by electron microscopy with immunogold labelling. In the immunogold
      localization studies P1 protein was detected in association with the cytoplasmic
      inclusion bodies characteristic of PVY infections and in the cytoplasm of the
      infected plant cells. No significant P1 antibody binding with other plant cell
      organelles, or with the cell wall and plasmodesmata, was detected by immunogold
      labelling.

PMID- 9780036
TI  - Specific inclusion bodies are associated with replication of lettuce infectious
      yellows virus RNAs in Nicotiana benthamiana protoplasts.
AB  - Nicotiana benthamiana mesophyll protoplasts, either mock-inoculated or inoculated
      using in vitro transcripts derived from lettuce infectious yellows virus (LIYV)
      RNA 1- and/or RNA 2-cloned cDNAs were analysed by transmission electron
      microscopy (TEM) and, in some cases, also by immunogold labelling. TEM revealed
      the main cytopathological effects of LIYV infections in N. benthamiana
      protoplasts infected with RNAs 1 and 2: (a) typical closterovirus-induced (beet
      yellows virus-type) accumulations of vesiculated cytoplasmic membranes as
      inclusion bodies, sometimes with associated virions; (b) scattered aggregations
      of virions within the cytoplasm; and (c) electron-dense plasmalemma deposits.
      These were not seen in mock-inoculated protoplasts. Protoplasts inoculated only
      with LIYV RNA 1 contained vesiculated cytoplasmic inclusion bodies, but not
      virions or plasmalemma deposits. Thus, infection by only LIYV RNA 1 is sufficient
      to induce characteristic closterovirus vesiculated cytoplasmic inclusion bodies.
      However, both LIYV RNAs 1 and 2 are needed for production of virions and
      plasmalemma deposits.

PMID- 9780038
TI  - Association of sequences in the coat protein/readthrough domain of potato mop-top
      virus with transmission by Spongospora subterranea.
AB  - A monofungal culture of Spongospora subterranea was unable to acquire and
      transmit the T isolate of potato mop-top pomovirus (PMTV-T), which has been
      maintained by manual transmission in the laboratory for 30 years. A recently
      obtained field isolate (PMTV-S) was efficiently acquired and transmitted by the
      same fungus culture. Sequence analysis of the readthrough (RT) protein-coding
      region of PMTV-S showed the presence of an additional 543 nt in the 3' half of
      the coding region relative to that of PMTV-T. These additional nucleotides
      preserved the reading frame of the RT protein and inserted 181 amino acids into
      the RT protein. This was confirmed by a comparison by immunoblotting of the sizes
      of the RT protein of PMTV-T and other recent isolates of PMTV.

PMID- 9780037
TI  - Diversity among isolates of squash mosaic virus.
AB  - cDNA clones of RNA-2 of two isolates of squash mosaic virus (SqMV) were
      constructed and sequenced, revealing 87% sequence similarity. In Northern blot
      hybridization analyses, DNA probes made from these clones defined two SqMV
      hybridization subgroups. This grouping was verified by reciprocal hybridizations
      of purified RNA from five SqMV isolates, as probed with cDNA made from a member
      of each subgroup. Comparison of the RNA-2 sequence among the two SqMV isolates,
      and the reported sequence of other comoviruses, showed that SqMV constitutes one
      of four major branches in a phylogenetic tree of the genus. Analysis of the
      terminal noncoding sequences showed that although potentially similar folding
      patterns may form, neither nucleotide sequence nor secondary structural elements
      are highly conserved among comoviruses. In vitro translation products from
      purified RNA-1 of each subgroup (encoding the viral proteases) were found to
      process the polyprotein generated by in vitro translation of purified RNA-2 from
      either subgroup.

PMID- 9780039
TI  - Nucleotide sequence, genetic organization and expression strategy of the double
      stranded RNA associated with the '447' cytoplasmic male sterility trait in Vicia
      faba.
AB  - The entire nucleotide sequence of the double-stranded (ds) RNA associated with
      the unconventional '447' cytoplasmic male sterility (CMS) trait in Vicia faba was
      determined from overlapping cDNA clones and by RT-PCR. Confirming previous
      observations, it was found that the negative-strand was continuous and 17,635 nt
      long, while the positive-strand featured an interruption, probably a nick, that
      could potentially define two subgenomic RNAs of 2735 nt and 14,900 nt, with the
      smaller RNA being located on the 5' side. The entire positive-strand could encode
      a single in-frame ORF starting at the first AUG at position 42-44 and ending with
      a TGA at 17,517-17,519. This long potential polypeptide with a predicted
      molecular mass of 654,109 is the largest described to date in the plant kingdom
      and contains conserved amino acid sequence motifs typical of viral helicases and
      RNA-dependent RNA polymerases (RDRP). Only limited sequence homology was detected
      with the ORF B encoded by the hypovirulence-associated dsRNA of chestnut blight
      fungus, a dsRNA replicon similarly contained in host-derived membranous vesicles
      and considered to share a common ancestry with potyviruses. By contrast, the
      helicase and RDRP domains were in the same respective arrangement and shared
      extensive sequence homologies with those identified in the polyprotein encoded by
      the dsRNA isolated from Japonica rice, another dsRNA replicon featuring a
      specific nick in the positive-strand. Although no proteolytic self-cleavage
      activity has yet been demonstrated, it appears likely that this long ORF is a
      polyprotein that undergoes proteolytic maturation, with one of the polypeptides
      derived by self-cleavage being the determinant of the CMS trait.

PMID- 9780040
TI  - Translation efficiencies of the 5' untranslated region from representatives of
      the six major genotypes of hepatitis C virus using a novel bicistronic reporter
      assay system.
AB  - The 5' untranslated region (5'UTR) of hepatitis C virus (HCV) contains an
      internal ribosome entry site (IRES) which directs translation of the viral open
      reading frame (ORF). The 5'UTR is highly conserved between virus isolates in both
      primary sequence and predicted secondary structure. We cloned and sequenced the
      5' regions (nt 18 of the 5'UTR to nt 15 of the core coding sequence) of HCV
      isolates representing the six major genotypes and subcloned these into a
      bicistronic, dual luciferase reporter construct. The relative expression of the
      two luciferases, one directed by the HCV IRES and the other by cap-dependent
      ribosome scanning, was used to compare the activities of the different IRES
      elements in transfected cells. The 5'UTR from a genotype 2b isolate was the most
      efficient at directing translation in all four cell lines tested: BHK-21, HeLa
      T4+, HuH7 and HepG2. In HepG2 cells the 2b 5'UTR was three times as efficient as
      the type 6a 5'UTR, which was generally the least active IRES tested. These data
      suggest that HCV isolates are not able to translate their ORF with equal
      efficiency, and provide a starting point from which further sequence-function
      studies can be undertaken.

PMID- 9780041
TI  - In vitro infection of adult normal human hepatocytes in primary culture by
      hepatitis C virus.
AB  - In vitro infection of adult normal human hepatocytes in primary culture has been
      performed for investigating the replication cycle of hepatitis C virus (HCV) in
      differentiated cells. Hepatocytes were prepared from liver tissue resected from
      donors who tested negative for HCV, and inoculation was performed 3 days after
      plating with 33 HCV serum samples of different virus load and genotype. The
      presence of intracellular HCV RNA, detected by a strand-specific rTth RT-PCR
      assay, was used as evidence of infection. A kinetics analysis of HCV replication
      revealed that intracellular negative-strand RNA appeared at day 1 post-infection
      with a maximum level at days 3 and 5, followed by a decrease until day 14. At day
      5, we estimated that the copy level of viral RNA was amplified at least 15-fold
      in infected cells. The level of intracellular HCV RNA in response to different
      serum samples was reproducible from one hepatocyte culture to another, suggesting
      that there is no inter-individual variability in the susceptibility of
      hepatocytes to HCV infection. These findings indicate that adult human
      hepatocytes in primary culture retain their susceptibility to in vitro HCV
      infection and support HCV RNA replication. This model should represent a valuable
      tool for the study of initial steps of the HCV replication cycle and for the
      evaluation of antiviral molecules.

PMID- 9780042
TI  - West Nile virus envelope proteins: nucleotide sequence analysis of strains
      differing in mouse neuroinvasiveness.
AB  - Several neuroinvasive and non-neuroinvasive West Nile (WN) viruses were
      characterized by nucleotide sequencing of their envelope (E) protein regions.
      Prolonged passage in mosquito cells caused loss of neuroinvasiveness and
      acquisition of an N-linked glycosylation site, which is utilized. Limited passage
      in cell culture also caused glycosylation but not attenuation, suggesting that
      glycosylation may not be directly responsible for attenuation and that a second
      mutation (L68 --> P) may also be involved. A monoclonal antibody-neutralization
      escape mutant with a substitution at residue 307, a site common to other
      flavivirus escape mutants, was also attenuated. A partially neuroinvasive
      revertant regained the parental E sequence, implying that determinants outside of
      the E region may also influence attenuation. Data suggest that the neuroinvasive
      determinants may be similar to those for other flaviviruses. Also, sequence
      comparison with the WN virus (Nigeria) strain revealed considerable divergence of
      the E protein at the nucleotide and amino acid levels.

PMID- 9780043
TI  - The antiviral compound ribavirin modulates the T helper (Th) 1/Th2 subset balance
      in hepatitis B and C virus-specific immune responses.
AB  - Ribavirin is effective in combination therapies against chronic hepatitis C virus
      (HCV) infection, although its direct antiviral properties are unclear. We
      therefore studied the immune-modulatory effects of ribavirin on hepatitis B virus
      (HBV)- and HCV-specific immune responses. During a 24 week placebo-controlled
      ribavirin trial in ten patients with chronic HCV infection, HCV antibodies and
      alanine aminotransferase (ALT) levels decreased transiently whereas the serum
      levels of HCV RNA remained stable. Effects of ribavirin on human and murine
      phytohaemagglutinin (PHA)-activated T cells included inhibition of in vitro
      proliferation and modulation of IL-2, IL-4, IFN-gamma and TNF-alpha levels. HBcAg
      and HBeAg-specific IL-2 and IFN-gamma levels were > or = 25-fold higher in mice
      immunized with HBV core- or e-antigens (HBcAg, HBeAg) while receiving ribavirin
      compared to untreated mice, but IL-4 and IL-6 remained constant. Concordantly, a
      slight shift was observed in the IgG subclass distribution of the humoral
      responses of ribavirin-treated mice to HBeAg and HCV NS3 protein. Ribavirin
      treatment of HBeAg-transgenic (HBeAg-Tg) mice induced a dose-dependent down
      regulation of T helper (Th)2-mediated antibody production to HBeAg. In ribavirin
      treated HBeAg-Tg mice anti-HBe IgG1 (positively regulated by Th2 cytokines)
      decreased simultaneously as both anti-HBe IgG2a (positively regulated by Th1
      cytokines) levels and in vitro T-cell IFN-gamma production increased, indicating
      a change in the Th1/Th2 balance. Thus, the present data suggest that ribavirin is
      not strictly an antiviral compound, but rather it alters the T-cell balance in
      the immune system.

PMID- 9780044
TI  - Cell-to-cell spread of poliovirus in the spinal cord of bonnet monkeys (Macaca
      radiata).
AB  - In order to study the spread of poliovirus in the spinal cord of bonnet monkeys,
      10(8) TCID50 Mahoney strain of poliovirus was inoculated into the ulnar nerves of
      monkeys that were subsequently autopsied on days 1, 2, 3, 6, 9, 12, 14, 15 and 16
      postinoculation (p.i.). Virus spread in the spinal cord, the accompanying
      histopathological changes and paralysis occurred in a cervico-thoraco-lumbar
      direction. Virus reached the cervical region of the spinal cord within the first
      3 days and subsequently spread to all segments of the spinal cord. In situ
      hybridization demonstrated viral RNA initially in the cervical neurons on day 3
      p.i. and in the anterior horn neurons of lumbar segments of the spinal cord by
      day 6 p.i. Loss of Nissl substance in some of the anterior horn neurons was
      apparent on day 3 p.i. in the cervical and thoracic regions and by day 6 p.i. in
      the lumbar region. In the lumbar region, neuronophagia was a consistent feature
      which was observed on days 6-9 p.i., followed by neuronal dropouts on day 12 p.i.
      and thereafter. In the cervical and thoracic region, reappearance of Nissl
      substance was apparent from day 12 p.i. Upper limb paralysis preceded lower limb
      paralysis (5.5+/-1.73 vs 8.18+/-2.18, P = 0.046), further suggesting that virus
      spread within the spinal cord was via an intraneural route despite persistent
      viraemia detectable from day 2 p.i. onwards. The temporal distribution of the
      virus spread, distribution of viral RNA, histopathological and clinical changes
      indicate a cell-to-cell spread of poliovirus in the CNS, having gained access to
      the CNS from the peripheral nerve.

PMID- 9780045
TI  - The Semliki Forest virus vector induces p53-independent apoptosis.
AB  - Three deletion mutants of the structural protein region of the Semliki Forest
      virus (SFV) genome, including one which encompassed all the viral structural
      protein genes, induced apoptosis in BHK cells at 48 h after transfection, as
      shown by DNA laddering and TUNEL staining, as did the wild-type SFV4 RNA. A
      similar result was obtained for the SFV1 expression vector, which has a
      multicloning site inserted in place of the structural protein genes. However, in
      cells transfected with viral RNA containing a deletion of the nsP2 gene, neither
      viral RNA synthesis nor the induction of apoptosis occurred. Both SFV1 vector and
      wild-type SFV4 RNA induced apoptosis in human H358a lung carcinoma cells, which
      have a homozygous deletion of the p53 gene. It is concluded that the SFV vector
      encodes a function in the nonstructural coding region which induces p53
      independent apoptosis and is dependent on viral RNA synthesis.

PMID- 9780046
TI  - Pathogenesis of pneumovirus infections in mice: detection of pneumonia virus of
      mice and human respiratory syncytial virus mRNA in lungs of infected mice by in
      situ hybridization.
AB  - The pathogenesis of pneumonia virus of mice (PVM) and human respiratory syncytial
      virus (HRSV) in BALB/c mice were investigated by using in situ hybridization to
      detect virus mRNA in fixed lung sections. Following intranasal inoculation with
      120 p.f.u. PVM the pattern of hybridization showed that virus mRNA was initially
      detected within 2 days in alveolar cells. As the infection progressed the number
      of hybridizing alveolar cells increased and signal was also detected in cells
      lining the terminal bronchioles. By days 4 to 5 post-infection areas of
      morphological abnormality could be seen, particularly in the strongly hybridizing
      regions of the lung, and this correlated with the appearance of clinical signs of
      infection. In animals which survived the infection virus-specific mRNA could not
      be detected 10 days post-infection. Mice infected with 1500 p.f.u. HRSV showed
      significant differences in the distribution of virus-specific mRNA when compared
      to the pattern seen with PVM. HRSV mRNA was detected over large areas, but
      predominantly in peribronchiolar and perivascular regions of the lungs 5 days
      post-infection. The yield of PVM from infected mouse lungs was considerably
      higher than that of HRSV. The possible implications of these results for the use
      of the mouse model for pneumovirus infections are discussed.

PMID- 9780047
TI  - Nucleotide sequences of the trailer, nucleocapsid protein gene and intergenic
      regions of Newcastle disease virus strain Beaudette C and completion of the
      entire genome sequence.
AB  - The nucleotide sequences of the nucleocapsid protein (NP) gene, the intergenic
      regions in the nucleocapsid protein (NP)-phosphoprotein (P), P-matrix protein (M)
      and M-fusion glycoprotein gene junctions and the trailer region of a virulent
      Newcastle disease virus (NDV) strain Beaudette C were determined. The NP gene is
      1747 nt long and encodes a protein of 489 amino acids. Each of the intergenic
      sequences determined is 1 nt long and, including the previously published
      intergenic sequences, the gene junction sequences varied in length from 1-47 nt
      and lacked any sequence identity. The 5' trailer region is 113 nt in length.
      Comparison of the sequences of the terminal leader and trailer regions of
      Beaudette C strain with those of nonvirulent strain B1 showed a high level of
      conservation, indicating the likelihood of these elements not being a factor in
      virulence. Together with previously published data, this report completes the
      sequence of the 15,186 nt genomic RNA of NDV strain Beaudette C.

PMID- 9780048
TI  - M protein correlates with the receptor-binding specificity of haemagglutinin
      protein of reassortant influenza A (H1N1) virus.
AB  - From the reassortment experiments between A/Aichi/4/92 and A/WSN/33 (WSN) (H1N1)
      viruses, two different phenotype viruses which contained the haemagglutinin (HA)
      gene from A/Aichi/4/92 virus and the neuraminidase (NA) gene from WSN virus were
      obtained. PW13 and PW15 viruses agglutinated chicken red blood cells (CRBC),
      while PW10 and PW70 viruses did not. However, the expressed HA proteins of these
      viruses did not adsorb CRBC. The difference in gene constellation between PW13,
      PW15 and PW10, PW70 viruses was the membrane protein (M) gene. The former two had
      the M gene from A/Aichi/4/92 virus and the latter two had that from WSN virus. In
      PW15-infected cells, haemadsorption of CRBC was observed 30 min later than that
      of goose red blood cells and the M1 protein migrated from the nucleus to the
      cytoplasm 30 min earlier than adsorption of CRBC was observed. On the other hand,
      in PW10-infected cells, haemadsorption of CRBC was not observed through the virus
      replication and the M1 protein stayed in the nucleus after HA and NA activities
      reached maximum levels. Co-expression of the M and the HA proteins of
      A/Aichi/4/92 virus did not help the HA protein gain the ability to adsorb CRBC.
      However, neuraminidase treatment of COS cells expressing the HA protein of
      A/Aichi/4/92 virus or MDCK cells infected by PW10 virus restored the ability to
      adsorb CRBC. We discussed the possibility that the M1 protein helped the NA
      protein in its role to modify the HA protein on the cell surface.

PMID- 9780049
TI  - The M1 and NP proteins of influenza A virus form homo- but not heterooligomeric
      complexes when coexpressed in BHK-21 cells.
AB  - The nucleoprotein (NP) and matrix protein (M1) are the most abundant structural
      proteins of influenza A virus. M1 forms a protein layer beneath the viral
      envelope and NP constitutes the protein backbone of the ribonucleoproteins
      (RNPs). In order to elucidate the functions of these proteins in virus assembly
      we have expressed NP and M1 in BHK-21 cells using Semliki Forest virus replicons
      and analysed their molecular interactions. We found that both M1 and NP engaged
      in extensive homooligomerization reactions soon after synthesis. However, there
      was no detectable heterooligomerization taking place between the two viral
      proteins, nor between these and host proteins. One interpretation of these
      results is that homooligomers, and not monomers, of NP and M1 are used as
      building blocks during RNP assembly and formation of the submembranous M1 layer,
      respectively. The complete absence of M1-NP heterooligomers suggests, on the
      other hand, that these two major viral proteins do not interact directly with
      each other during virus assembly. We also found that a fraction of M1 associated
      with cellular membranes. This did not, however, result in membrane budding or
      vesicularization as was the case with the matrix protein of vesicular stomatitis
      virus when expressed separately (P. A. Justice and others, Journal of Virology
      69, 3156-3160, 1995).

PMID- 9780050
TI  - Enhancement of human immunodeficiency virus type 1 infectivity by Nef is producer
      cell-dependent.
AB  - The growth kinetics of wild-type and nef mutant viruses of human immunodeficiency
      virus type 1 were comparatively analysed in several human CD4+ cell lines.
      Delayed replication of nef mutant virus was observed in all cell lines examined.
      To determine the stage in the virus replication cycle that is affected by Nef, a
      single-round replication assay was performed. Initially, the expression of marker
      genes in transfected cells was examined in order to study the role of Nef in the
      late phase of infection. The results obtained indicated that Nef is dispensable
      during the transcription to virion production stage. Next, the effect of Nef on
      the early phase was investigated with a single-round infection. It was
      demonstrated that Nef is required in the early phase of the virus replication
      cycle, from virion adsorption to integration. Finally, the infectivity of virus
      stocks prepared from four cell lines was determined. The relative infectivity of
      the nef mutant from the four cell lines differed. Taken together, we conclude
      that Nef acts via modulation of viral particles to enhance virus infectivity in a
      cell-dependent manner.

PMID- 9780051
TI  - Human immunodeficiency virus type 1 in faeces and serum: evidence against
      independently evolving subpopulations.
AB  - It is not known whether independent tissue-specific evolution accounts for the
      differences between human immunodeficiency virus type 1 (HIV-1) subpopulations in
      intestinal tissue and blood. To study this, sequential serum samples from three
      persons were analysed for the presence of HIV-1 V3 genotypes which were detected
      exclusively in faeces at a specific time-point. For two persons the faeces
      genotype was found in serum samples collected before the time of faeces
      collection: 7 months for one person and 32 months for the other person. In the
      third person, serum collected 1 month after faeces collection contained the
      faeces genotype in abundance. These data indicate that a difference between
      intestinal tissue and blood HIV-1 subpopulations is not the result of complete
      compartmentalization and independent HIV-1 evolution in intestinal tissue, but
      that it reflects an unequal distribution of HIV-1 in different tissues.

PMID- 9780052
TI  - Determinants of disease in the simian immunodeficiency virus-infected rhesus
      macaque: characterizing animals with low antibody responses and rapid
      progression.
AB  - Clinical and laboratory markers of simian immunodeficiency virus (SIV) infection
      were studied during the first 3 months after intravenous inoculation of rhesus
      macaques. Virus-binding serum antibody titres were correlated strongly with
      disease progression (P < 0.005) and were predictive of disease outcome by 7 weeks
      after inoculation. Low virus-binding serum antibody responses to SIV occurred in
      animals that also showed acute depletion of circulating CD20+ B cells. Acute
      damage to the CD4+ T cell and CD20+ B cell populations rendered some animals
      incapable of mounting virus-specific antibody responses and these macaques became
      the rapidly progressing cases comprising approximately 20-30% of infected animal
      cohorts.

PMID- 9780053
TI  - Human Th1 and Th2 T-cell clones are equally susceptible to infection and
      immortalization by human T-lymphotropic virus type I.
AB  - Human CD4+ Th1 and Th2 clones were infected with human T-lymphotropic virus type
      I (HTLV-I) and followed up for a 12 month period in culture. PCR analysis showed
      that proviral DNA and viral mRNA were present in both Th1 and Th2 infected
      clones, throughout the entire culture period. Thus, HTLV-I exhibited neither
      preferential tropism nor exerted differential immortalizing activity in Th1
      versus Th2 cells. All the infected clones immediately lost their antigen
      dependency for growth and continuously proliferated in IL-2-conditioned medium
      without need for additional stimulation. Infected Th1 and Th2 clones equally
      showed high expression of CD25, HLA-DR, CD44, CD30 and CD45RO. Infection with
      HTLV-I altered the cytokine profile in Th1 and Th2 clones. Both types of clones
      produced IL-6 and TNF-alpha. Th1 infected clones retained their ability to
      secrete IFN-gamma, but lost IL-2 gene expression. Th2 infected clones lost IL-4
      gene expression, retained the ability to produce small amounts of IL-5 and
      acquired IFN-gamma expression.

PMID- 9780054
TI  - Bluetongue virus core protein VP4 has nucleoside triphosphate phosphohydrolase
      activity.
AB  - The intact virion of bluetongue virus comprises ten segments of dsRNA enclosed in
      two concentric protein capsids. The core, which is transcriptionally active,
      includes three minor proteins (VP1, VP4 and VP6) which are considered to be the
      candidates for the core-associated enzymes that transcribe and modify full-length
      mRNA copies for each of the ten genome segments. Using purified recombinant VP4
      protein and core-like particles containing VP4, in this report it is demonstrated
      that VP4 has nucleoside triphosphatase (NTPase) activity. VP4 is a nonspecific
      NTPase that hydrolyses four types of ribonucleoside triphosphate (NTP) to the
      corresponding nucleoside diphosphate. The substrate preference was
      GTP>ATP>UTP>CTP. NTP hydrolysis by VP4 was maximal when the Mg2+ or Ca2+ ion
      concentrations were 4 mM or 6 mM, respectively. The presence of single-stranded
      polynucleotides poly(A), poly(U) and poly(C) had little effect on the NTPase
      activity. Although the enzyme exhibited a broad temperature optimum around 40
      degrees C, the pH optimum was sharp, between pH 7.5 and 8. The Km and Vmax of ATP
      hydrolysis were calculated to be 0.25+/-0.05 microM ATP and 55+/-4 pmol ATP
      hydrolysed min(-1) microg(-1), respectively. The Km was affected by the addition
      of poly(A) to only a small extent in contrast to the Vmax, which was increased by
      at least twofold.

PMID- 9780055
TI  - Comparative sequence analysis of American, European and Asian isolates of viruses
      in the genus Coltivirus.
AB  - In this study, the basis for the classification of virus isolates grouped within
      the genus Coltivirus, family Reoviridae, is discussed. Sequences of dsRNA
      segments from American (segments 9-12), European (segment 12) and Asian (segments
      7-12) isolates were characterized and polythetic criteria were defined for their
      taxonomic classification. These criteria (including sequence analysis) permitted
      the different species to be distinguished and classified into two groups. In both
      groups, subgroups were defined according to the degree of homology between the
      genomic sequences. American and European isolates are classified within group A,
      which includes subgroups A1 (Colorado tick fever virus species) and A2 (Eyach
      virus species). Asian isolates are classified in group B, which includes
      subgroups B1 (JKT-7075 virus species) and B2 (JKT-6423 virus species). The
      proteins encoded by the sequenced genomic segments were analysed. This allowed
      the identification of dsRNA binding domains in the proteins encoded by segment 8
      of subgroup B1 isolates and segment 12 of subgroup B2 isolates. A conserved
      pattern of amino acids in segment 7 of group B isolates matched sequences found
      in the catalytic domains of protein kinases.

PMID- 9780056
TI  - Phylogenetic analysis of 22 complete genomes of the human polyomavirus JC virus.
AB  - The polyomavirus JC (JCV) establishes a persistent infection in the kidneys, and
      is the virus agent that causes the demyelinating disease progressive multifocal
      leukoencephalopathy. PCR and DNA sequence analyses of partial JCV genomes have
      shown that there are at least four main JCV types, each associated with a
      specific geographical region. Type 1 is of European origin, Type 2 is Asian, Type
      3 is found in individuals of African decent and Type 4 is a potential recombinant
      of Types 1 and 3, and is widely distributed throughout the population of the
      United States. A comprehensive phylogenetic analysis of 22 complete JCV genomes
      excluding part of the regulatory region was accomplished using neighbour-joining,
      UPGMA and maximum parsimony methods. The resulting UPGMA and parsimony
      phylogenies suggest that the European Type 1 strains diverged from the other
      types during the evolution of JCV and that each of the other genotypes (and
      subtypes) falls into well-supported clades. This is the first whole genome
      approach to phylogeny reconstruction for JCV and represents a significant
      improvement over earlier studies that were limited to partial JCV sequences and
      the neighbour-joining method.

PMID- 9780057
TI  - Four geographically distinct genotypes of JC virus are prevalent in China and
      Mongolia: implications for the racial composition of modern China.
AB  - JC polyomavirus (JCV) is ubiquitous in humans, persisting in renal tissue and
      excreting progeny in urine. It has been shown that the genotyping of urinary JCV
      offers a novel means of tracing human migrations. This approach was used to
      elucidate the racial composition of modern China. JCV isolates in the Old World
      were previously classified into nine distinct genotypes. One of them (B1) has a
      wide domain, encompassing part of Europe and the entirety of Asia. By
      constructing a neighbour-joining phylogenetic tree, all B1 isolates detected so
      far were classified into four distinct groups (B1-a to -d), each occupying unique
      domains in the world. According to this revised classification system of JCV
      DNAs, four genotypes (CY, SC, B1-a and -b) were found to be prevalent in China
      and Mongolia (Mongolia was studied instead of Inner Mongolia, which is part of
      China). There was a remarkable variation in the incidence of genotypes among the
      sites of sample collection. CY was more frequently detected in Northern China, SC
      was predominant in Southern China and B1-b was detected only in Mongolia. B1-a
      was spread throughout China. These data were statistically analysed and the
      observed regional differences in the incidence of genotypes were found to be
      significant. It is likely that these differences in JCV distribution in China
      reflect the intermingling of different population groups that constitute modern
      China.

PMID- 9780058
TI  - Sequence and transcriptional analysis of terminal regions of the fowl adenovirus
      type 8 genome.
AB  - Fowl adenovirus (FAdV) type 1, CELO strain has no homologies to mastadenovirus
      E1A, E1B, E3 and E4, which regulate virus gene expression, DNA replication and
      virus-host interaction. Similarly, the right 5 kb and left 15 kb ends of CELO
      virus DNA are non-homologous to mastadenoviruses. To compare CELO virus with
      another FAdV, 7.5 kb of the left and 17 kb of the right ends of FAdV type 8
      (strain A-2A) were sequenced and nine and 17 open reading frames (ORFs),
      respectively, were found. This FAdV-8 genome was similar to CELO virus in that
      (1) the central region contained the major structural protein genes including the
      fibre, pVIII, 100K, late 33K and pIVa2 genes, which were in the same order as in
      mastadenoviruses, (2) no homologues of mastadenovirus E1A, E1B, E3 and E4 were
      found in the ends, and (3) the left 6 kb and the right 13 kb ends showed no
      homology to mastadenoviruses. Several genomic features were unique to FAdV-8
      compared to CELO virus. FAdV-8 contained one fibre gene in contrast to two in
      CELO virus. Three of eight unassigned ORFs in the left and five of 13 unassigned
      ORFs in the right ends were unique compared to CELO virus. Two sets of tandem
      repeats, one with five identical 33 bp repeats and the other with more than ten
      identical 135 bp repeats, mapped between 4.5 and 7.5 kb from the right terminus.
      No virus-associated RNA gene was found. Fifteen of 16 unique FAdV-8 ORFs tested
      were, as determined by RT-PCR, transcribed early.

PMID- 9780059
TI  - Differences in the intracellular localization and fate of herpes simplex virus
      tegument proteins early in the infection of Vero cells.
AB  - The fate of herpes simplex virus 1 (HSV-1) tegument proteins during infection in
      Vero cells was investigated immunochemically. Input virion-associated VP13/14 and
      VP16 localized to the nucleus early in infection, while VP1/2 localized to the
      nuclear envelope of the cell and VP22 could not be detected using monoclonal
      antibody P43. Western blotting suggested that virion-associated VP13/14, VP16 and
      VP22 were stable in infected cells whereas VP1/2 appeared to be processed or
      modified. Further studies showed that P43 recognized a phosphorylation-sensitive
      epitope in VP22 and suggested that virion-associated VP22 was phosphorylated upon
      entry to the cell. VP13/14 and VP16 were easily extracted from cells early in
      infection whereas VP22 was largely insoluble. Phosphatase treatment of soluble
      extracts caused a shift in the molecular mass of VP16 showing it was
      phosphorylated. As infection progressed VP16 was observed in discrete nuclear
      compartments where it co-localized with ICP8 and the capsid-associated protein
      VP22a. VP13/14 was also observed in the nucleus. P43 immunostaining appeared
      around 6 h post-infection as punctate nuclear foci which often localized to the
      edge of VP16-immunoreactive areas. Punctate P43 cytoplasmic staining appeared
      around 12 h post-infection. By 18 h the nuclear pattern had disappeared and an
      extensive cytoplasmic stain was observed which closely overlapped that of other
      tegument proteins. On the basis of these data we suggest that virion-associated
      VP22 is phosphorylated upon entry of the virus into the cell and that
      unphosphorylated VP22, which is preferentially recognized by P43, becomes
      available later in infection, initially in the nucleus, for packaging into
      virions.

PMID- 9780060
TI  - Identification of a novel multifunctional structural domain in the herpes simplex
      virus type 1 genome: implications for virus latency.
AB  - A domain, previously termed RE1, exists within the herpes simplex virus type 1
      genome potentially influencing expression of immediate early genes and the
      latency associated transcripts. This domain consists of 10 tandem copies of a CT
      rich sequence. We demonstrate that this domain binds multiple host-cell factors
      that may allow RE1 to act either as a transcriptional regulator and/or to affect
      nucleosomal and DNA structure in the latent genome.

PMID- 9780061
TI  - Binding of human cytomegalovirus to sulfated glucuronyl glycosphingolipids and
      their inhibitory effects on the infection.
AB  - Interactions between human cytomegalovirus (HCMV) and various carbohydrate
      structures were analysed using sulfated glucuronyl glycosphingolipids (SGGLs) and
      the structurally related glycosphingolipids (GLs). A thin-layer chromatography
      overlay assay and a solid-phase binding assay revealed that HCMV strongly bound
      to sulfated glucuronyl lactosaminylparagloboside, one of the SGGLs having the
      repeating lactosamine structure (3Gal beta1-4GlcNAc1-)2 in addition to the 3-O
      sulfated glucuronyl moiety. The virus bound less strongly to other 3-O-sulfated
      GLs, which included sulfated glucuronyl paragloboside and cerebroside sulfate
      ester, and also to (3Gal beta1-4GlcNAc1-)2-containing GLs that included nLc6Cer.
      Thus, a (3Gal beta1-4GlcNAc1-)2 and a 3-O-sulfated saccharide seem to be
      important structures for the binding by HCMV. When virus particles were
      preincubated with these GLs, inhibitory effects were observed both on expression
      of the viral immediate-early gene and on plaque formation by HCMV. These effects
      were very well correlated with the abilities of the GLs to bind to the virus.
      Pretreatment of host cells with HNK-1 monoclonal antibody, which specifically
      recognizes SGGLs, resulted in partial inhibition of plaque formation by HCMV.
      These results clearly show that HCMV recognizes and binds to the sulfated
      carbohydrate structure in SGGL and also suggest that binding of HCMV to the
      specific sugar structure may play an important role in HCMV infection.

PMID- 9780062
TI  - African swine fever virus NL gene is not required for virus virulence.
AB  - Previously, we described a highly conserved nonessential African swine fever
      virus (ASFV) right variable region gene, NL. Deletion of NL from the European
      pathogenic isolate E70 resulted in almost complete attenuation of the virus in
      domestic swine. To study gene function further, NL gene deletion mutants were
      constructed from two pathogenic African ASFV isolates, Malawi Lil-20/1 (Mal) and
      Pretoriuskop/96/4 (Pr4). Unexpectedly, both Mal (Mal-deltaNL) and PR4
      (Pr4deltaNL) null mutants remained highly virulent when inoculated in swine. Mal
      deltaNL exhibited a disease and virulence phenotype indistinguishable from its
      revertant, Mal-NLR, which caused 100% mortality. Mortality among Pr4deltaNL
      infected animals was also high; however, a significant delay in onset of fever
      and viraemia and in time to death was observed. These data indicate that NL gene
      function is not required for ASFV virulence and that other yet-to-be identified
      viral determinants perform significant virulence functions in these African field
      isolates.

PMID- 9780064
TI  - Prion distribution in hamster lung and brain following intraperitoneal
      inoculation.
AB  - Prion titres were measured in the lungs and brains of Syrian hamsters after
      intraperitoneal inoculation with sucrose gradient-purified 263K prions
      (approximately 10(8) LD50). Prions were detected in the lung of one hamster on
      day 7, but were not detected in the lungs of any other hamster until day 71.
      Prions were detected in the lungs of all hamsters sampled thereafter but titres
      remained low through day 127. Prions were first detected in the brain on day 35
      and brain titres increased exponentially until day 127 with a doubling time of
      about 4.5 days. On day 133, titres averaged 10(8.0) LD50/g in brain and 10(5.0)
      LD50/g in lung. Two out of the five remaining hamsters were clinically normal but
      prion titres were not significantly different from those in the clinically
      affected hamsters. Thus, significant prion titres may be found outside the CNS in
      clinically normal hamsters.

PMID- 9780063
TI  - Polyhedrin sequence determines the tetrahedral shape of occlusion bodies in
      Thysanoplusia orichalcea single-nucleocapsid nucleopolyhedrovirus.
AB  - A nucleopolyhedrovirus (NPV) isolated from the looper Thysanoplusia orichalcea L.
      (Lepidoptera: Noctuidae) (ThorNPV) is occluded in a tetrahedral protein matrix.
      The ORF of the ThorNPV polyhedrin gene contains 738 nt which code for 246 amino
      acids of the putative polyhedrin protein with an estimated molecular mass of
      28,778 Da. The promoter of this gene is similar in length to the promoter of
      Spodoptera frugiperda NPV (SfMNPV), with a 5 nt deletion before the start codon
      compared to those of other NPVs. When the polyhedrin gene of Autographa
      californica NPV (AcMNPV), whose occlusion bodies (OBs) are polyhedral, was
      replaced by the polyhedrin gene of ThorNPV, which produces tetrahedral OBs,
      tetrahedral polyhedra with properly occluded virions were produced. This work
      establishes the importance of the polyhedrin protein sequence in determining OB
      shape. Leucine at position 43 of ThorNPV polyhedrin was identified as responsible
      for the tetrahedral shape of ThorNPV OBs by PCR-based site-directed mutagenesis.
      Susceptibility to alkaline buffer of OBs formed by recombinant AcMNPV (RECAcV)
      carrying the polyhedrin gene of ThorNPV was slightly greater than that of native
      ThorNPV OBs. The LD50 of RECAcV for third-instar beet armyworm (Spodoptera
      exigua) was significantly lower than that of AcMNPV (253 and 31 OBs per larva,
      respectively).

PMID- 9780065
TI  - The point prevalence of otitis media with effusion among school children in
      Greece.
AB  - Tympanometry, pneumatic otoscopy and acoustic reflex tests performed on 5121
      school children aged 6-12 years old, during late spring and early autumn of 1996.
      Demographic, social, medical and birth related data were collected for each child
      separately. The study was undertaken in order to evaluate the prevalence of
      otitis media with effusion in a sample of the general population in Greece and to
      investigate the correlations with possible risk factors. A total of 6.5% had
      unilateral or bilateral type B or C2 tympanogramms, and negative reflex
      suggestive of otitis media with effusion. The finding indicates a rather low
      prevalence of otitis media with effusion in school children in Greece compared
      with other countries. This study, also has shown that there was a statistical
      significant relationship between secretory otitis media (SOM) and, age, sex,
      mother's education, parental smoking, breast-feeding, allergy and previous otitis
      media. No correlation was found in relation to the climate of residence,
      premature birth, number of siblings, mother's gestational age, birth skull
      circumference, birth body weight and length.

PMID- 9780066
TI  - Acoustic rhinometric evaluation of nasal cavity and nasopharynx after
      adenoidectomy and tonsillectomy.
AB  - The occurrence of upper airway obstruction is frequently seen in patients with
      adenotonsillar hypertrophy. These patients usually also show hypertrophied
      inferior turbinates even without any other nasal or sinus disease. However, it is
      not known what the effect of adenoidectomy and tonsillectomy is on these
      hypertrophic turbinates. To determine the effect of these procedures on the nasal
      and nasopharyngeal geometry, we performed acoustic rhinometry previous to and 2
      weeks following adenoidectomy and tonsillectomy, before and after spraying a
      decongestant in 31 children (19 males, 12 females; mean age, 8.03 years). After
      the adenoidectomy and tonsillectomy, there were increases in the cross-sectional
      area at the anterior end of the inferior turbinate (0.53+/-0.03 cm2
      preoperatively, 0.65+/-0.21 cm2 postoperatively; P=0.01), the nasal volume
      (7.13+/-1.78 cm3 preoperatively, 9.38+/-1.65 cm3 postoperatively; P < 0.01), the
      cross-sectional area at the adenoid (0.80+/-0.53 cm2 preoperatively, 1.83+/-0.81
      cm2 postoperatively; P < 0.01) before decongestion. However, 10 min after
      decongestion there was only a significant increase of the cross-sectional area at
      the adenoid (1.08+/-0.12 cm2 preoperatively, 1.80+/-0.20 cm2 postoperatively;
      P=0.01). We conclude that adenoidectomy and tonsillectomy reverse the congestion
      of the inferior turbinate which is observed in children with adenotonsillar
      hypertrophy and that acoustic rhinometry can be used to evaluate the effect of
      adenoidectomy and tonsillectomy on the nose and nasopharynx.

PMID- 9780067
TI  - Mitomycin-C in the treatment of tracheal cicatrix after tracheal reconstruction.
AB  - OBJECTIVE: To demonstrate the potential use of Mitomycin-C (MMC) in the treatment
      of difficult and recurrent tracheal stenosis. DESIGN: Case series. SETTING:
      Tertiary care setting. PATIENTS: A retrospective chart review was performed on
      five pediatric patients with severe, recurrent tracheal granulation and cicatrix
      after tracheal reconstruction who were treated with topical MMC as an adjunct to
      bronchoscopy and laser treatment. MMC was applied intraoperatively on saturated
      pledgets at a dose of 0.1 mg/ml for 2 min to the area where the cicatrix had been
      lysed. The five patients were able to be decannulated. DISCUSSION: Mitomycin-C is
      an anti metabolite known to inhibit fibroblast proliferation in vitro. This agent
      has been used with a high success rate in glaucoma filtration surgery to promote
      patency of the trabecula. The results of this preliminary application in the
      pediatric airway as well as the mechanism of action will be discussed.

PMID- 9780069
TI  - Epidemiology and etiology of acquired hearing disorders in childhood in the
      Cologne area.
AB  - Because of their serious consequences for all aspects of development, severe
      hearing disorders in children are an important clinical entity. A better
      understanding of the epidemiology and etiology of acquired hearing disorders may
      potentially lead to more effective prevention. Marked differences in the
      epidemiology of acquired hearing disorders are reported in the literature. In
      order to illuminate the problem of acquired disorders and to define current
      etiological causes with special regard to ethnological factors in the Cologne
      area, we started a retrospective study. A total of 314 children in residence at
      the school for hearing impaired children in Cologne were investigated. We also
      obtained concise data on the structure of the population in order to determine
      prevalence of acquired hearing disorders in the German and immigrant portions of
      the population. We found an overall prevalence of 0.43 per thousand for severe
      hearing disorders and deafness. German children were most frequently affected by
      acquired, and non-German children by hereditary hearing disorders. The most
      common causes of acquired severe hearing disorder were the perinatal complex of
      premature delivery, anoxia and hyperbilirubinuria or kernicterus. Other causes
      were congenital rubella infections and meningitis in early childhood. The
      accumulation of perinatal etiologies seems to be the reason for the remarkable
      majority of acquired hearing disorders among German children. One reason might be
      progress in neonatology which exerts two effects. It decreases perinatal
      mortality but increases perinatal complications like acquired hearing impairment.
      The incidence of congenital rubella in Germany has decreased during recent years,
      reaching a low level.

PMID- 9780068
TI  - Hearing deficits at school age; the predictive value of otitis media in infants.
AB  - AIM: To evaluate the long-term predictive value of persistent/recurrent otitis
      media with effusion (OME) in infants in relation with hearing levels at (early)
      school age. DESIGN: A case-cohort study among a population-based sample of school
      age children screened for hearing deficits. POPULATION AND METHODS:
      Schoolchildren (second grade, 5-6 years of age) in the city of Utrecht, the
      Netherlands, who failed the hearing screening test and a sample of children
      invited for this screening. History of otitis media (serosa and acute) was
      assessed using three sources of information: a self-completion questionnaire
      mailed to the parents; medical records of otolaryngology visits; data from the
      (Ewing) hearing screening test at 9 months of age. RESULTS: Children who failed
      the primary Ewing test and children with recurrent and or persistent OME in the
      first 2 years of life showed an increased risk of failing school audiometry
      compared to children without such an OME history (OR=1.6 and 2.3, respectively).
      In a logistic model, the results of the primary Ewing test and the frequency of
      acute otitis media, proved to be moderately predictive for the screening test
      result at school age. CONCLUSION: OME in infants is a prognostic factor for
      hearing performance in the early school years.

PMID- 9780070
TI  - Expression of CD34-antigen in nasopharyngeal angiofibromas.
AB  - Formalin-fixed, paraffin-embedded and frozen tissues of 24 patients with primary
      nasopharyngeal angiofibroma, of whom seven had recurrences, were studied
      immunohistochemically for the expression of CD34 antigen using two different
      antibodies (HPCA-1 and QBEND 10). In all cases, there was an exclusive staining
      of endothelial cells, while pericytes, smooth muscle cells and stromal
      fibroblasts were not reactive. The staining intensity, however, was more
      pronounced in small tumor vessels of capillary- and sinusoidal-type than in
      larger vessels, which were usually characterized by an irregular smooth muscle
      coat. This differential staining indicates an increased proliferative potential
      of the endothelium of the small vessel component of nasopharyngeal angiofibroma
      (neoangiogenesis) and an inhibitory influence of vascular smooth muscle cells on
      endothelial cell growth. Moreover, the positive immunoreaction of all endothelial
      cells for CD34 is indicative of the absence of lymphatic vessels, which confirms
      previous ultrastructural observations. No differences in the staining pattern
      were observed between primary versus recurrent tumors, formalin fixed, paraffin
      embedded versus snap-frozen acetone fixed material, or between both CD34
      antibodies. Our findings indicate that nasopharyngeal angiofibroma is a
      vasoproliferative malformation.

PMID- 9780072
TI  - Otoacoustic emissions in screening cleft lip and/or palate children for hearing
      loss--a feasibility study.
AB  - Patients with cleft lip and/or palate abnormalities are likely to suffer
      permanent conductive (PCHL) or sensorineural hearing loss (SNHL) due in part to
      the association with syndromes known to include PCHL or SNHL. The presence of
      otitis media, a nearly universal complication in these patients, makes
      identifying the hearing impaired in this population a challenge, since the
      detection of permanent hearing loss is made more difficult. This problem might be
      overcome by using click-evoked otoacoustic emissions (CEOAE's) shortly after
      birth. Twenty-one out of 28 newborns presented to the regional cleft palate team
      were eligible for CEOAE screening shortly after birth. Among these 21 infants,
      five had anomalies other than cleft lip and/or palate associated with an
      increased risk for hearing impairment. At the first CEOAE screening (ILO88
      Emission Analyser, mean age 3 weeks, range 1-11 weeks) clear CEOAE's were present
      in all of the 18 ears of nine infants with isolated lip and/or jaw clefts. In 24
      ears of 12 infants with palatal clefts, CEOAE's were present in only six ears
      (three infants), not demonstrable due to noisy registration in another six ears
      and absent in 12 ears despite a quiet registration. During follow-up of those who
      failed the first screening (18 ears, nine infants), normal hearing was found in
      14 ears (seven infants) and sensorineural hearing loss was documented in four
      ears (two infants). CEOAE screening in infants with isolated lip and/or jaw
      clefts seems feasible and effective. In infants with palatal clefts an auditory
      brain stem screening might be more appropriate.

PMID- 9780071
TI  - A cross-sectional study of speech- and language-abilities of children with normal
      hearing, mild fluctuating conductive hearing loss, or moderate to profound
      sensoneurinal hearing loss.
AB  - A total of 1528 pre-school children (mean age 4 years and 9 months), being
      identified as speech or language delayed, were evaluated with respect to micro
      otoscopy, nose and throat pathology, hearing function, and speech-language
      abilities. Subjects were classified into groups of (I) constant normal hearing,
      (II) fluctuating conductive hearing loss and (III) bilateral moderate to profound
      sensorineural hearing loss requiring hearing aids. In groups II and III, severe
      speech and language pathologies were found more frequently than in group I.
      Additionally, auditory perception skills were less in group II, even if
      peripheral hearing function was normalized. Group III was affected more than
      group II, but not significantly. The results indicate that in children having
      speech or language delay for severals reasons, mild fluctuating hearing loss can
      additionally alter language acquisition, but less than in cases of moderate or
      profound sensoneurinal hearing loss. The need of early detection of sensoneurinal
      hearing loss appears widely accepted; this study demonstrates also the necessity
      of early diagnosis of mild fluctuating hearing loss, especially in children with
      speech-language delay.

PMID- 9780073
TI  - Complicated neonatal submandibular suppurative sialadenitis.
AB  - Acute suppurative infection of salivary glands in the neonatal period is a rare
      entity; and almost always involves the parotid glands. A rare case of neck
      abscess in association with right submandibular suppurative sialadenitis in a 7
      day-old baby is presented. The possible etiology, diagnosis, and management of
      this uncommon disease are discussed.

PMID- 9780074
TI  - Acute airway obstruction in Hunter syndrome.
AB  - Hunter syndrome is one of the mucopolysaccharidoses, characterized by a
      deficiency of the lysosomal enzyme iduronate sulfatase. Among its physical
      manifestations, there are numerous head and neck signs, including characteristic
      facial features, macroglossia and short neck. The accumulation of
      glycosaminoglycans in the soft tissues of the head and neck can be associated
      with acute airway obstruction. We report a 7 year old boy with Hunter syndrome
      who developed acute airway compromise requiring an emergency tracheotomy. A
      review of the literature of airway management in patients with this disease is
      also presented.

PMID- 9780075
TI  - A role for genetic predisposition in subglottic stenosis.
AB  - We present the development of ASGS in two of three premature male triplets; the
      affected infants were monozygotic, while the unaffected triplet was dizygotic.
      All three shared remarkably similar risk factor profiles. There is suggested the
      existence of a genetic factor or factors which may predispose certain infants to
      the development of ASGS. The expression of such genetic influence may be
      expressed through the a priori presence of CSGS or other genetically based
      mechanisms including abnormal cartilage growth or development, specific patterns
      of chondral or mucosal injury, the action of specific growth factors, or the
      effects of autoimmune or inflammatory mediators. We propose that genetic
      predisposition be considered a possible risk factor in the development of
      subglottic stenosis.

PMID- 9780076
TI  - European Consensus Statement on Neonatal Hearing Screening. Finalised at the
      European Consensus Development Conference on Neonatal Hearing Screening, 15-16
      May 1998, Milan.

PMID- 9780078
TI  - Autoradiographic distribution of neuropeptide tyrosine binding sites in the brain
      of the African lungfish, Protopterus annectens.
AB  - The distribution of neuropeptide tyrosine (NPY) binding sites in the brain of the
      African lungfish, Protopterus annectens, was studied by autoradiography using
      radioiodinated NPY as a tracer. The highest concentrations of binding sites were
      found in the dorsal and intermediate parts of the medial pallium, the dorsal
      pallium, and in the medial and lateral subpallium. These observations, together
      with the finding of a moderate density of binding sites in the olfactory bulbs,
      suggest that NPY may be involved in the processing of olfactory information
      and/or neuromodulation of limbic activities. High densities of binding sites were
      also found in several rhombencephalic nuclei, including the nucleus fascicoli
      solitarii, the nucleus motorius nervi vagi, the spinal motor column and all
      components of the reticular formation, indicating that NPY may play a role in the
      regulation of neurovegetative functions. Concurrently, the presence of high
      concentrations of binding sites in the hypophysis suggests that, in the lungfish,
      NPY may exert a direct control of pituitary hormone secretion.

PMID- 9780077
TI  - Cerebrospinal fluid tau protein is not elevated in HIV-associated neurologic
      disease in humans. HIV Neurobehavioral Research Center Group (HNRC).
AB  - We measured the concentrations of the neuron-specific protein, tau, in the
      cerebrospinal fluid (CSF) of 32 neurologically characterized HIV-infected
      (HIVpos) subjects and nine matched seronegative (HIVneg) controls using a
      sensitive ELISA assay. Of 32 HIVpos subjects, nine had HIV-associated
      neurocognitive disorders, and nine had clinically diagnosed peripheral
      neuropathies. CSF tau levels in subjects with HIV-associated neurocognitive
      disorders were similar to those in HIVneg subjects (185 +/- 83 vs. 223 +/- 106
      pg/ml; P = 57). CSF tau levels in HIVpos subjects with peripheral neuropathies
      did not differ from those without neuropathies (320 +/- 190 vs. 251 +/- 185; P =
      23). In summary, CSF tau levels were not elevated in patients with HIV-associated
      neurologic disease.

PMID- 9780079
TI  - Transient expression of calretinin in the trout habenulo-interpeduncular system
      during development.
AB  - Calcium-binding proteins control calcium homeostasis during neural development.
      The expression of one of these proteins, calretinin (CR), was monitored by
      immunohistochemistry in the developing habenulo-interpeduncular system of the
      rainbow trout, a conserved region of the brain along vertebrate phylogeny that
      undergoes a neurochemical reorganization in late development. No CR
      immunoreactivity was observed in the habenulo-interpeduncular system during the
      embryonic development. CR-immunolabeling appeared in newly hatched fry and during
      the fry development the number of CR-immunostained elements increased
      progressively. During the juvenile stages (from 30 days post-hatching onwards) a
      gradual decrease in the number of CR-immunostained cells occurred, until its
      complete disappearance in adults. These variations in CR expression may represent
      the variable calcium-buffering needs during different developmental stages.

PMID- 9780080
TI  - Modulatory role of acetylcholine in the rat pineal gland.
AB  - The function of acetylcholine (ACh) in the mammalian pineal gland is unknown. To
      test the hypothesis that ACh exerts a modulatory role in this organ, in the
      present study electrophysiogical multiunit recordings were carried out in ex-vivo
      rat pineal glands superfused with different drugs. It was found that ACh (10(-7)
      M) as well as the cholinergic agonists oxotremorine (10(-7) M) and nicotine (10(
      6) M) increased the discharge rates of most of the spontaneously active units and
      led to burst activity in previously regularly firing cells. It is concluded that
      ACh may play a modulatory role in the pineal by influencing the firing of a
      special population of pineal cells with perhaps receptor function.

PMID- 9780081
TI  - Pattern of apolipoprotein D immunoreactivity in human brain.
AB  - Presence of intracytoplasmatic apolipoprotein D (apo D), a lipophilic ligand
      transporter, was investigated in normal human brains between 20 and 55 years,
      using an anti-human apolipoprotein D antibody and extravidin-biotin-enhanced
      immunohistochemistry. Apo D immunoreactivity was found in neuroglial cells of
      white matter in all sampled brain regions studied but also in pial cells and
      perivascular cells. Immunoreactive neurons do not present a uniform pattern
      throughout the gray matter. The pons and the brainstem show a high
      immunoreactivity for apo D in several nuclei (olivary, arciforme, cuneado,
      raphe). In the cerebellum the immunoreactivity appears in some neurons of the
      Purkinje layer. Finally in the cerebral cortex apo D positive neurons were not
      observed. These results suggest that apo D role may vary depending of cellular
      synthesis or location.

PMID- 9780082
TI  - Postnatal development of dopamine and serotonin transporters in rat caudate
      putamen and nucleus accumbens septi.
AB  - Density of dopamine transporter (DAT) and serotonin transporter (5-HTT) membrane
      proteins in the caudate-putamen (CPu) and nucleus accumbens (NAc) of rat brain
      was assessed at seven ages at postnatal days (PD) 7-60, by in vitro quantitative
      autoradiography. Binding of [3H]GBR-12935 (to DAT) and [3H]paroxetine (to 5-HTT)
      increased steadily and very similarly, from low levels at PD-7 to maximal levels,
      to 6-7-fold higher density at PD-60 in both regions. These findings indicate that
      DAT and 5-HTT follow a synchronized course of development in rat CPu and NAc. In
      contrast to reported elimination of excessive receptors in CPu and NAc during
      maturation, there was no evidence of pruning of DAT or 5-HTT in these regions of
      rat forebrain.

PMID- 9780083
TI  - A novel model of primary and secondary hyperalgesia after mild thermal injury in
      the rat.
AB  - Secondary hyperesthesia was investigated in a rat thermal injury model. After a
      mild focal thermal injury (52 degrees C/45 s) to the rat heel, the response
      latency for a thermal stimulus directed at the injured site was reduced (10 --> 6
      s; e.g. primary thermal hyperalgesia) but no change was seen at the distal site.
      Conversely, tactile threshold at the distal site was significantly reduced (15 -
      > 5 g; e.g. secondary tactile allodynia) but much less so at the injured site.
      Magnitude of the secondary tactile allodynia paralleled the severity of the
      primary injury. Accordingly, this model has the same characteristics seen in
      human post-tissue-injury hyperesthetic states and provides a tool for the study
      of mechanisms underlying primary and secondary hyperesthesia.

PMID- 9780085
TI  - Responses of axotomized afferents to blockade of nitric oxide synthesis after
      spinal nerve lesion in the rat.
AB  - Lesioned afferents were tested for their responses to blockade of nitric oxide
      synthesis in the spinal nerve L5 lesion model for neuropathic pain in Wistar
      rats. Seven single fibers with spontaneous activity split from dorsal root L5
      showed no response after non-selective blockade of nitric oxide synthesis with
      N(G)-nitro-L-arginine methyl ester whereas five were excited after 5-7 min. Three
      previously silent units were recruited. Blood flow in the dorsal root ganglion
      decreased. None of fifteen axotomized afferents tested responded to selective
      blockade of neuronal nitric oxide synthesis with 7-nitroindazole. It is concluded
      that neuronal nitric oxide is not involved in the generation of spontaneous
      activity in axotomized afferent neurons in this model. We suggest that the
      vasoconstriction induced by blockade of endothelial nitric oxide may be
      responsible for the excitatory responses.

PMID- 9780084
TI  - Protein kinase C-zeta activity but not level is decreased in Alzheimer's disease
      microvessels.
AB  - While there is considerable evidence demonstrating altered activity of the major
      isoforms of protein kinase C (PKC) in the vasculature and neurons of Alzheimer
      disease (AD) brains, little is known about the activity and/or levels of the
      atypical PKC isoforms. The objective of this study is to compare PKC-zeta
      activity and level in cerebral microvessels isolated from AD brains with
      microvessels from the brains of nondemented age-matched controls. Measurements of
      the kinase activity reveals that the PKC-zeta activity is significantly (P <
      0.01) lower in AD brain microvessels compared with vessels from control brain.
      Despite this decrease in enzyme activity, the level of PKC-zeta, assessed by
      Western blot, is significantly (P < 0.01) elevated in AD microvessels. These data
      demonstrate significant and divergent changes in the PKC-zeta activity and level
      in the microcirculation of the AD brain and suggest that aberrant regulation of
      microvascular PKC-zeta could contribute to the abnormal signaling mechanisms at
      the blood-brain barrier in the AD brain.

PMID- 9780086
TI  - Distribution of P2X3 receptors in the rat trigeminal ganglion after inferior
      alveolar nerve injury.
AB  - The ATP-gated cation channel receptor P2X3 is associated with nociceptive primary
      sensory neurons. We have, using immunohistochemistry, examined the expression of
      P2X3 in rat trigeminal ganglia 4-22 days after ligation/section or chronic
      constriction of the mandibular inferior alveolar nerve. In the normal trigeminal
      ganglion the anti-P2X3 receptor antibody labeled 37-58% of all neurons. Double
      labeling demonstrated that about 70-95% of the small neurons that bind the
      isolectin I-B4 displayed P2X3-immunoreactivity, and that about 40% of larger RT97
      positive nerve cells were P2X3 receptor-immunoreactive. At 4 and 10 days after
      inferior alveolar nerve injury, the proportion of P2X3-immunoreactive neurons had
      increased to about 65% (range 52-78%). Examinations at the injury sites showed an
      intense P2X3 receptor-immunoreactivity in nerve endings. At longer survival
      stages the proportion of P2X3 receptor-positive sensory neurons had returned to
      control values. These results show that the P2X3 receptor is transiently
      upregulated and anterogradely transported in trigeminal primary sensory neurons
      after nerve injury. Since the receptor is accumulated in injured nerve endings,
      it may be associated with abnormal impulse propagation from these sites.

PMID- 9780087
TI  - Paradoxical metabolic response of the human brain to a single electroconvulsive
      shock.
AB  - Regional brain protein synthesis was evaluated with positron emission tomography
      (PET) and L-(S-[11C]methyl)methionine ([11C]MET) in depressive patients, before
      and 3 h after an electroconvulsive shock (ECS), when energy supply is restored,
      and in healthy volunteers. Depressive patients presented apparent lower protein
      synthesis than normals, in agreement with known reduction of cerebral activity.
      In contrast, ECS resulted in a significant increase (56%, P < 0.05) in global
      cortical protein synthesis. This paradoxical hyperactivation of cellular protein
      metabolism in response to seizures and the fact that synaptic activity is further
      reduced after electroconvulsive therapy (ECT), may provide new insights for
      understanding the mechanism of action of ECT.

PMID- 9780088
TI  - Kinetics of activation of a Ca2+-dependent K+ current induced by flash photolysis
      of caged carbachol in isolated guinea-pig outer hair cells.
AB  - It has been shown that the application of acetylcholine activates a Ca2+
      dependent K+ current in outer hair cells, and the resulting hyperpolarization is
      thought to be an important part of the inhibition mediated by cholinergic
      efferent nerve fibres to the cochlea. In order to study the kinetics of the
      current, flash photolysis has been used to apply a cholinergic agonist,
      carbachol, rapidly to isolated outer hair cells. A delay in the onset of the
      outward potassium current following photorelease of carbachol was consistently
      observed, and the activation phase of the response could be described by a
      sigmoidal-like function with a mean delay of 59 ms and time constant of 71 ms.
      The sum of these values lies within the time scale reported for the onset of the
      inhibition following electrical stimulation of the efferent nerves. Although a
      distinct current attributable to an acetylcholine receptor was not visible in
      these experiments, indirect evidence for a carbachol-induced influx of Ca2+ was
      obtained.

PMID- 9780089
TI  - Apolipoprotein E polymorphism influences the cerebral metabolic pattern in
      Alzheimer's disease.
AB  - In 49 patients with the clinical diagnosis of probable Alzheimer's disease (AD)
      apoE genotyping as well as regional cerebral glucose metabolism (rCMRGI) using
      positron emission tomography (PET) of [18F]2-fluoro-2-deoxy-D-glucose (FDG) were
      studied. The metabolic pattern was condensed to a ratio by dividing the rCMRGI of
      typically affected regions (temporo-parietal and frontal association cortex) by
      the rCMRGI of the least affected regions (primary cortical areas, basal ganglia,
      cerebellum and brainstem). Epsilon4-heterozygotes and epsilon4-homozygotes were
      grouped together, and also those lacking the epsilon4-allele (non-epsilon4). For
      the metabolic pattern we found a significant correlation to severity of dementia
      in both groups (epsilon4: r = 0.49, P = 0.05; non-epsilon4: r = 0.59, P = 0.006).
      On ANCOVA severity of dementia and epsilon4 status were independent predictors of
      the cerebral metabolic pattern (P = 0.01). These differences may be attributed to
      epsilon4 dependent histopathologic changes.

PMID- 9780091
TI  - Projections from the caudal spinal trigeminal nucleus to commissural interneurons
      in the supratrigeminal region: an electron microscope study in the rat.
AB  - Electron microscopic double-labeling study in the rat indicated that projection
      fibers from the caudal spinal trigeminal nucleus (Vc) were distributed
      ipsilaterally within the supratrigeminal region (STR) capping the trigeminal
      motor nucleus (Tm) and made synaptic contact with neurons projecting to the
      contralateral Tm. Nociceptive inputs to the Vc may reflexly control, via
      interneurons in the STR, the activities of Tm neurons innervating the
      masticatory, tensor tympani, and/or tensor veli palatine muscles.

PMID- 9780090
TI  - Examination of colocalization of calcitonin gene-related peptide- and substance P
      like immunoreactivity in the knee joint of the dog.
AB  - It is generally assumed that the majority of substance P (SP)-containing
      afferents are also immunoreactive for calcitonin gene-related peptide (CGRP). In
      order to determine whether this is also the case in articular afferents where the
      contents of these peptides are low, we carried out a double labeling study using
      Fast Blue (FB) as a retrograde tracer injected into the center of the knee joint
      cavity of the dog together with immunohistochemistry for SP and CGRP. After 7-36
      days of survival, dorsal root ganglia (DRGs, L4-S1) were removed. Labeled cells
      were found mainly (94%) in L5 - 6 DRGs, and SP- and CGRP-like immunoreactivity
      was found in about 17 and 29% of FB-labeled cells, respectively. The coexistence
      of SP and CGRP was observed in 10.4% of articular afferents and only 62.7% of SP
      positive articular neurons contained CGRP, a much lower ratio than in other
      afferents of the dog such as testicular afferents. Our data suggest that these
      peptides are not always released together and that they do not always work
      together in the joint under normal conditions.

PMID- 9780092
TI  - Reaction times of head movements occurring in association with express saccades
      during human gaze shifts.
AB  - During lateral gaze shifts to a visual target of 10 degrees eccentricity, the gap
      paradigm (presence of a 200 ms gap between offset of fixation lamp and onset of
      target lamp) produced a significant decrease in the reaction times (RTs) of head
      movements (54 ms) and saccades (82 ms) when compared with those obtained under
      the overlap paradigm across five subjects. Correlation coefficients between the
      RTs of saccades and head movements were significantly lower under the gap
      paradigm than those under the overlap paradigm. Particularly, the RTs of head
      movements occurring in association with express saccades were independent of the
      saccade RTs. These results indicate that the head and eye motor systems are
      controlled by the separate neural mechanisms in the conditions which produce
      express saccades.

PMID- 9780093
TI  - Comparison of glaucomatous progression between untreated patients with normal
      tension glaucoma and patients with therapeutically reduced intraocular pressures.
      Collaborative Normal-Tension Glaucoma Study Group.
AB  - PURPOSE: To determine if intraocular pressure plays a part in the pathogenic
      process of normal-tension glaucoma. METHODS: One eye of each eligible subject was
      randomized either to be untreated as a control or to have intraocular pressure
      lowered by 30% from baseline. Eyes were randomized if they met criteria for
      diagnosis of normal-tension glaucoma and showed documented progression or high
      risk field defects that threatened fixation or the appearance of a new disk
      hemorrhage. The clinical course (visual field and optic disk) of the group with
      lowered intraocular pressure was compared with the clinical course when
      intraocular pressure remained at its spontaneous untreated level. RESULTS: One
      hundred-forty eyes of 140 patients were used in this study. Sixty-one were in the
      treatment group, and 79 were untreated controls. Twenty-eight (35%) of the
      control eyes and 7 (12%) of the treated eyes reached end points (specifically
      defined criteria of glaucomatous optic disk progression or visual field loss). An
      overall survival analysis showed a statistically significant difference between
      the two groups (P < .0001). The mean survival time +/-SD of the treated group was
      2,688 +/- 123 days and for the control group, 1,695 +/- 143 days. Of 34 cataracts
      developed during the study, 11 (14%) occurred in the control group and 23 (38%)
      in the treated group (P = .0075), with the highest incidence in those whose
      treatment included filtration surgery. CONCLUSIONS: Intraocular pressure is part
      of the pathogenic process in normal-tension glaucoma. Therapy that is effective
      in lowering intraocular pressure and free of adverse effects would be expected to
      be beneficial in patients who are at risk of disease progression.

PMID- 9780094
TI  - The effectiveness of intraocular pressure reduction in the treatment of normal
      tension glaucoma. Collaborative Normal-Tension Glaucoma Study Group.
AB  - PURPOSE: In a companion paper, we determined that intraocular pressure is part of
      the pathogenesis of normal-tension glaucoma by analyzing the effect of a 30%
      intraocular pressure reduction on the subsequent course of the disease. We report
      an intent-to-treat analysis of the study data to determine the effectiveness of
      pressure reduction. METHODS: One eligible eye of 145 subjects with normal-tension
      glaucoma was randomized either to no treatment (control) or to a 30% intraocular
      pressure reduction from baseline. To be eligible for randomization, the normal
      tension glaucoma eyes had to show documented progression of field defects or a
      new disk hemorrhage or had to have field defects that threatened fixation when
      first presented for the study. Survival analysis compared time to progression of
      all randomly assigned patients during the course of follow-up from the initial
      baseline at randomization. In a separate analysis, data of patients developing
      cataracts were censored at the time that cataract produced 2 lines of Snellen
      visual acuity loss. RESULTS: Visual field progression occurred at
      indistinguishable rates in the pressure-lowered (22/66) and the untreated control
      (31/79) arms of the study (P = .21). In an analysis with data censored when
      cataract affected visual acuity, visual field progression was significantly more
      common in the untreated group (21/79) compared with the treated group (8/66). An
      overall survival analysis showed a survival of 80% in the treated arm and of 60%
      in the control arm at 3 years, and 80% in the treated arm and 40% in the controls
      at 5 years. The Kaplan-Meier curves were significantly different (P = .0018). The
      analyses gave different results because of a higher incidence of cataract in the
      group that underwent filtration surgery. CONCLUSIONS: The favorable effect of
      intraocular pressure reduction on progression of visual change in normal-tension
      glaucoma was only found when the impact of cataracts on visual field progression,
      produced largely by surgery, was removed. Lowering intraocular pressure without
      producing cataracts is beneficial. Because not all untreated patients progressed,
      the natural history of normal-tension glaucoma must be considered before
      embarking on intraocular pressure reduction with therapy apt to exacerbate
      cataract formation unless normal-tension glaucoma threatens serious visual loss.

PMID- 9780095
TI  - Prevalence of blindness and cataract surgery in Shunyi County, China.
AB  - PURPOSE: To estimate the prevalence of blindness and cataract surgery among older
      adults in rural China. METHODS: Cluster sampling was used in randomly selecting
      men and women aged 50 years or older for visual acuity testing and an eye
      examination in 28 villages in Shunyi County. The survey, which was carried out in
      the fall of 1996, was preceded by a pilot study in which operational methods were
      refined and quality assurance evaluations carried out. RESULTS: Of 5,555
      enumerated subjects > or =50 years of age, 91.5% (5,084/5,555) were examined and
      90.9% (5,052/5,555) were tested for visual acuity. In this population, 2.8%
      (139/5,052) were blind, defined as presenting visual acuity less than 6/60 in
      both eyes. Blindness was associated with older age and female sex. Cataract was
      the principal cause of blindness in at least one eye in 48.2% (67/139) of blind
      people. The ratio of those blind from cataract who were operated on to the those
      who could have been operated on, cataract surgical coverage, was estimated to be
      47.8% (54/113). Cataract surgery was associated with younger age but not sex or
      education. CONCLUSIONS: Blindness, particularly blindness related to cataract,
      continues to be a significant problem among the elderly, especially women, in
      this population-based sample of rural Chinese. Despite an active eye-care program
      in Shunyi County, only half of those who might benefit from cataract surgery are
      receiving it.

PMID- 9780096
TI  - Visual acuity and quality of life outcomes in patients with cataract in Shunyi
      County, China.
AB  - PURPOSE: To measure visual acuity and vision-related quality of life in
      individuals in rural China operated on for cataract. METHODS: Five thousand fifty
      two persons age 50 years and older, 90.9% (5,052/5,555) of a randomly selected
      population in Shunyi County, were examined in the fall of 1996. Visual
      functioning and quality of life questionnaires were administered to those with
      presenting visual acuity less than 6/60 in either eye and to those who were
      aphakic or pseudophakic. RESULTS: Of the 87 individuals operated on for cataract,
      12% (10/87) had presenting visual acuity of 6/18 or more in both eyes, and 24.1%
      (21/87) had less than 6/60. Twenty-five percent (29/116) of the 116 eyes operated
      on for cataract had presenting visual acuity of 6/18 or more, and 44.8% (52/116)
      had less than 6/60. Aphakic cases without glasses and uncorrectable aphakia
      attributable to surgical complications were common. In a multivariate regression
      model, including time period of surgery, hospital type, and surgical procedure,
      only pseudophakia was associated with better outcomes (P = .05). On a scale from
      0 (maximum problems) to 100 (no problems), the mean visual functioning score (+/
      SD) for the operated-on population was 61.9 +/- 30.0, and 71.0 +/- 31.8 for the
      quality of life questionnaire. These scores were comparable to those of the
      unoperated-on population with moderate bilateral blindness (<6/60 to > or =3/60
      in the better eye). Visual functioning and quality of life scores were closely
      correlated with visual acuity in operated-on (r = 0.64 and r = 0.61,
      respectively) and unoperated-on populations (r = 0.68 and r = 0.59,
      respectively). CONCLUSIONS: Both clinical and patient-reported cataract surgery
      outcomes are below what should be achievable. Improvement in outcomes must be
      given greater emphasis if the potential of cataract surgery in restoring sight is
      to be realized.

PMID- 9780097
TI  - Partial coherence interferometry: a novel approach to biometry in cataract
      surgery.
AB  - PURPOSE: To compare biometry performed by an enhanced version of dual beam
      partial coherence interferometry and applanation ultrasound in a prospective
      study of 85 cataract eyes to improve refractive outcome of cataract surgery due
      to a more accurate calculation of intraocular lens power. METHODS: The SRK II
      formula using ultrasound biometry data was employed. Three months after surgery,
      partial coherence interferometry biometry was repeated and refractive outcome was
      determined. Preoperative partial coherence interferometry biometry data were used
      to determine the refractive power of the intraocular lenses retrospectively and
      to calculate the possible refractive outcome. RESULTS: Precision of partial
      coherence interferometry biometry was more than 10 times better than that of
      ultrasound. Therefore, the possible mean absolute error for postoperative
      refraction achieved with partial coherence interferometry biometry was 0.49
      diopters (compared with 0.67 diopters with ultrasound biometry), resulting in an
      improvement of 27%. Axial eye length measured with the two techniques differed by
      a mean of 460 microm. The difference in lens thickness measured with partial
      coherence interferometry and ultrasound significantly correlated with cataract
      grade. A mean shortening of 120 microm of axial eye length following cataract
      surgery was also detected by partial coherence interferometry. CONCLUSIONS: The
      enhanced version of partial coherence interferometry offers biometry with
      unprecedented precision (<10 microm) and resolution (approximately 12 microm),
      therefore improving the refractive outcome in cataract surgery. This noninvasive
      technique provides a high degree of comfort for the patient, with no need for
      local anesthesia or pupil dilation and minimized risk of corneal infection.

PMID- 9780098
TI  - Two distinct kerato-epithelin mutations in Reis-Bucklers corneal dystrophy.
AB  - PURPOSE: Two patients were diagnosed with Reis-Bucklers corneal dystrophy (RBCD),
      although the pattern and severity of corneal opacification differed. To see
      whether there was a genetic basis for these phenotypic variations, we analyzed
      beta ig-h3, the gene that codes for kerato-epithelin and that contains a mutation
      (Arg555Gln) that causes RBCD. METHODS: A 30-year-old man with honeycomb-shaped
      subepithelial opacities in his central cornea and a 25-year-old man with
      progressive subepithelial geographic opacities were both considered to have RBCD.
      We isolated genomic DNA from leukocytes of the two patients and their family
      members and screened for an Arg555Gln kerato-epithelin mutation. Then we analyzed
      all exons of the gene using the single-strand conformation polymorphism (SSCP)
      technique to search for any other kerato-epithelin mutations. RESULTS: The
      patient with honeycomb-shaped opacities had an Arg555Gln kerato-epithelin
      mutation that caused his RBCD, whereas the patient with geographic opacities did
      not; instead, he had a new kerato-epithelin mutation (Arg124Leu), which
      cosegregated with his family members. CONCLUSIONS: The variant of RBCD
      characterized by honeycomb-shaped opacities is caused by an Arg555Gln kerato
      epithelin mutation. On the other hand, a new kerato-epithelin mutation,
      Arg124Leu, was found to cause the RBCD variant characterized by recurrent
      epithelial erosions and progressive geographic subepithelial opacification. Codon
      124 is a hot spot for kerato-epithelin mutations, where the mutations responsible
      for three autosomal dominant corneal dystrophies--lattice type I (Arg124Cys),
      Avellino (Arg124His), and the variant of RBCD with geographic rather than
      honeycomb opacities (Arg124Leu)--are located.

PMID- 9780099
TI  - Cytomegalovirus retinitis and viral resistance: 3. Culture results. CMV Retinitis
      and Viral Resistance Study Group.
AB  - PURPOSE: To evaluate the relationship between blood and urine cultures for
      cytomegalovirus and clinical outcomes in patients with cytomegalovirus retinitis.
      METHODS: Prospective epidemiologic study of 108 patients with newly diagnosed
      cytomegalovirus retinitis. Blood and urine were cultured for cytomegalovirus at
      diagnosis of retinitis, at 1 month and 3 months after diagnosis, and every 3
      months thereafter. RESULTS: Of the patients, 80.6% were found to have either a
      positive blood culture or urine culture for cytomegalovirus at the time of
      diagnosis of retinitis, and a positive blood culture at diagnosis was associated
      with an increased mortality (odds ratio = 1.91, P = .012). Follow-up cultures
      were positive in approximately 20% of patients, and the rate was constant over
      time. The development of a positive blood or urine culture during follow-up
      correlated with the occurrence of cytomegalovirus retinitis in the contralateral
      eye in those patients with unilateral disease at diagnosis (odds ratio = 5.74, P
      = .001). CONCLUSIONS: Patients with cytomegalovirus retinitis and positive blood
      cultures for cytomegalovirus have a poorer prognosis.

PMID- 9780101
TI  - Efficacy and safety of fluorescein angiography with orally administered sodium
      fluorescein.
AB  - PURPOSE: To report the efficacy and safety of fluorescein angiography after oral
      administration of fluorescein solution in a large number of patients during a
      period of 8 years. METHODS: A total of 1,787 patients (2,625 eyes) underwent
      fluorescein angiography after oral administration of sodium fluorescein at Hara
      Eye Hospital, Utsunomiya, Japan, between January 1989 and March 1997. The
      ingestible solution was 10 ml of 10% sodium fluorescein, the same material
      generally used for injection in conventional fluorescein angiography. Retinal
      photography began 15 minutes after ingestion and continued for 1 hour. The camera
      and the photography and film processing techniques were the same as those used
      for conventional fluorescein angiography using injected sodium fluorescein.
      RESULTS: In 2,554 (97.3%) of 2,625 eyes, photographs adequate for clinical use
      were obtained. In 1,787 patients, no anaphylactic or other severe adverse effects
      were observed, and only 31 patients (1.7%) experienced minimal itching,
      discomfort, or nausea after oral sodium fluorescein intake. For conditions such
      as central serous chorioretinopathy, retinal vein occlusion, diabetic
      retinopathy, and cystoid macular edema, sufficient information for clinical use
      was obtained. CONCLUSIONS: Fluorescein angiography using orally administered
      sodium fluorescein is generally effective and safe in standard clinical practice.

PMID- 9780100
TI  - Adjunctive daunorubicin in the treatment of proliferative vitreoretinopathy:
      results of a multicenter clinical trial. Daunomycin Study Group.
AB  - PURPOSE: To assess the efficacy and safety of adjunctive daunorubicin during
      vitrectomy surgery in eyes with idiopathic proliferative vitreoretinopathy (PVR).
      METHODS: Two hundred eighty-six eyes (286 patients) with stage C2 (Retina Society
      Classification, 1983) or more advanced preoperative PVR in which surgery with
      silicone oil was planned were enrolled in a multicenter, prospective, randomized,
      controlled clinical trial. Standardized surgery plus adjunctive daunorubicin
      perfusion was compared with surgery alone. Outcomes assessed were retinal
      attachment without additional vitreoretinal surgery 6 months after standardized
      surgery, number of and time until vitreoretinal reoperations within 1 year of
      standardized surgery, and change in visual acuity 1 year after standardized
      surgery, evaluated by photodocumentation, number of reoperations, and measurement
      of best-corrected visual function. Outcomes were determined 6 months after
      operation and reevaluated after 1 year of follow-up. RESULTS: Six months after
      standardized surgery, complete retinal reattachment without additional
      vitreoretinal surgery was achieved in 62.7% (89/142) of eyes in the daunorubicin
      group vs 54.1% (73/135) in the control group (P = .07, one-sided). However, in
      the daunorubicin group, significantly fewer vitreoretinal reoperations were
      performed within 1 year postoperatively (P = .005, one-sided) to achieve the same
      overall 1-year retinal reattachment rate (80.2% [105/131] vs 81.8% [103/126]).
      The rate of patients with no vitreoretinal reoperations was 65.5% (95/145) in the
      daunorubicin group vs 53.9% (76/141) in the control group. There was no
      difference in the best-corrected visual acuity. No severe adverse effect related
      to daunorubicin was identified. CONCLUSIONS: Although the rate of anatomic
      success after 6 months failed to show significance, some benefit of the
      adjunctive treatment exists, especially a tendency toward increased rate of
      reattachment and a significant reduction in the number of reoperations. This
      shows that human PVR is amenable to pharmacologic treatment.

PMID- 9780102
TI  - Ophthalmologic manifestations of internal carotid artery dissection.
AB  - PURPOSE: To report the ophthalmologic symptoms and signs associated with
      extracranial internal carotid artery dissection. METHODS: One hundred forty-six
      consecutive patients with extracranial internal carotid artery dissection were
      evaluted; 29 were studied retrospectively from 1972 to 1984 and 117 prospectively
      from 1985 to 1997. RESULTS: Sixty-two percent of patients (91/146) with
      extracranial internal carotid artery dissection had ophthalmologic symptoms or
      signs that were the presenting symptoms or signs of dissection in 52% (76/146).
      Forty-four percent (65/146) had painful Horner syndrome, which remained isolated
      in half the cases (32/65). Twenty-eight percent (41/146) had transient monocular
      visual loss, which was painful in 31 cases, associated with Horner syndrome in 13
      cases, and described as "scintillations" or "flashing lights"-often related to
      postural changes or exposure to bright lights-suggesting acute choroidal
      hypoperfusion in 23 cases. Four patients had ischemic optic neuropathy; one had
      diplopia. Among the 76 patients with ophthalmologic symptoms or signs as the
      presenting features of carotid dissection, a nonreversible ocular or hemispheric
      stroke later occurred in 27, within a mean of 6.2 days (range, 1 hour to 31
      days). Eighteen patients had a stroke within the first week after the onset of
      neuro-ophthalmic symptoms and signs, and 24 had a stroke within the first 2
      weeks. CONCLUSION: Ophthalmologic symptoms or signs are frequently associated
      with and are often the presenting features in internal carotid artery dissection.
      Painful Horner syndrome or transient monocular visual loss should prompt
      investigations to diagnose carotid artery dissection and begin early treatment to
      prevent a devastating ocular or hemispheric stroke.

PMID- 9780103
TI  - The treatment of normal-tension glaucoma.

PMID- 9780104
TI  - Studies of prevalence of blindness in the Asia-Pacific region and the worldwide
      initiative in ophthalmic education.

PMID- 9780105
TI  - Delayed dislocation of foldable plate-haptic silicone lenses after Nd:YAG laser
      anterior capsulotomy.
AB  - PURPOSE: To report two eyes (two patients) that had plate haptic silicone
      intraocular lenses that dislocated 4 weeks after Nd:YAG laser anterior
      capsulotomy to relieve capsular contraction. METHODS: Case reports. The clinical
      records of two patients were reviewed. RESULTS: After uncomplicated
      phacoemulsification with implantation of plate haptic silicone lenses in the
      capsular bag, two eyes of two patients developed visually notable early
      contraction of the capsulorhexis. Three radial-relieving incisions approximately
      1 mm long were made with a Nd:YAG laser in each eye to enlarge the capsulotomy.
      Although vision improved, both patients experienced sudden further reduction of
      vision after approximately 4 weeks. Upon examination of both patients, we noted
      an extension of an anterior radial capsulotomy incision peripherally, and the
      intraocular lenses had dislocated from the capsular bag into the ciliary sulcus.
      CONCLUSIONS: Tears may extend after radial-relieving incisions have been used to
      enlarge a contracted anterior capsulotomy, possibly because of continued capsular
      fibrosis. This may allow extrusion of a foldable intraocular lens from the
      capsular bag.

PMID- 9780106
TI  - Corneal lenticular wrinkling after automated lamellar keratoplasty.
AB  - PURPOSE: To report complications of automated lamellar keratoplasty in two eyes
      of two patients. METHODS: Case reports. Two eyes of two patients underwent
      automated lamellar keratoplasty for myopia. Both patients complained of visual
      distortion and glare in the postoperative eye. RESULTS: The postoperative eye of
      both patients showed evidence of wrinkling of the corneal lenticule accompanied
      by irregular astigmatism. Patient 1 showed persistent lenticular wrinkling and
      corneal scarring 2.5 years later. Patient 2 showed evidence of interface scar and
      overcorrection. CONCLUSION: The use of a microkeratome can be complicated by
      lenticular displacement and wrinkling, resulting in visual aberration for the
      patient.

PMID- 9780107
TI  - Laboratory diagnosis of Acanthamoeba keratitis using buffered charcoal-yeast
      extract agar.
AB  - PURPOSE: To evaluate the use of buffered charcoal-yeast extract agar for the
      isolation of Acanthamoeba from clinical specimens. METHODS: We retrospectively
      reviewed laboratory records of patients with ocular acanthamebic infection from
      October 1993 to September 1997 to compare the recovery of Acanthamoeba from
      clinical specimens inoculated onto various media. We then compared the
      experimental recovery of 10 corneal isolates of Acanthamoeba on buffered charcoal
      yeast extract and blood agars. RESULTS: Paired data for buffered charcoal-yeast
      extract and blood agars were available from 24 cultures performed in 13 cases of
      ocular acanthamebic infection. Acanthamebic trails were detected on both buffered
      charcoal-yeast extract and blood agars in nine cultures, only on buffered
      charcoal-yeast extract agar in nine cultures, and only on blood agar in one
      culture (P = .027). In the experimental study, all 10 clinical isolates produced
      trails on buffered charcoal-yeast extract agar, and the mean recovery after 10
      days of incubation ranged from 38% to 95% of the original inoculum number. For
      seven of the 10 isolates, more than 70% of the original inoculum was recovered on
      buffered charcoal-yeast extract agar. Only two of the 10 strains produced
      persistent trails on the blood agar, and the mean recoveries after 10 days of
      incubation were 0.67% and 1.17%. Recovery was significantly better on buffered
      charcoal-yeast extract agar than blood agar (P < or = .0003). CONCLUSION:
      Buffered charcoal-yeast extract agar is an excellent commercially available
      culture medium for the recovery of Acanthamoeba.

PMID- 9780108
TI  - Infection of the corneal endothelium in herpes simplex keratitis.
AB  - PURPOSE: To describe viral infection of the corneal endothelium in a patient with
      recurrent herpes simplex virus keratitis in the corneal graft. METHODS: Case
      report. A healthy 28-year-old man presented with necrotizing stromal keratitis
      and corneal perforation in the corneal graft. A second penetrating keratoplasty
      was performed. The corneal button was processed for histopathologic,
      immunohistochemical, and electron microscopic studies. RESULTS:
      Histopathologically, the corneal endothelium showed viral inclusion bodies.
      Herpes simplex virus antigens and viral particles were identified in stromal
      keratocytes and corneal endothelial cells. CONCLUSION: Productive herpes simplex
      virus infection of the corneal endothelial cells may contribute to corneal graft
      failure in recurrent herpes simplex virus infections.

PMID- 9780110
TI  - High-frequency Doppler ultrasound examination of blood flow in the anterior
      segment of the eye.
AB  - PURPOSE: To show that extending Doppler imaging into the high-frequency domain
      could allow detection and characterization of blood flow in small arterioles and
      capillaries. METHODS: A 40-MHz continuous wave Doppler system and a 60-MHz pulsed
      wave Doppler system were constructed, tested, and used to examine the ciliary
      body region in two normal volunteers. RESULTS: Ciliary body circulation in the
      region of the great circle of the iris, which is undetectable by conventional 7.5
      MHz duplex Doppler, was consistently and reproducibly detectable by high
      frequency (40-MHz and 60-MHz) Doppler systems. CONCLUSION: High-frequency Doppler
      imaging may provide a unique new tool for the characterization and assessment of
      anterior segment ocular blood flow.

PMID- 9780109
TI  - Recurrent nodular scleritis associated with varicella zoster virus.
AB  - PURPOSE: To describe a case of recurrent nodular scleritis that was apparently
      caused by reactivation of a varicella zoster virus infection. METHODS: Case
      report. Immunohistochemistry and polymerase chain reaction were used to detect
      viral antigen and DNA in the biopsy specimen of inflamed sclera of a patient with
      a history of recurrent nodular scleritis.

PMID- 9780111
TI  - Use of latanoprost in the treatment of glaucoma associated with Sturge-Weber
      syndrome.
AB  - PURPOSE: To determine if latanoprost reduces intraocular pressure in eyes with
      glaucoma associated with Sturge-Weber syndrome. METHODS: We conducted a
      prospective study in which eyes with uncontrolled intraocular pressure associated
      with Sturge-Weber syndrome were treated with latanoprost 0.005% once daily. All
      eyes were already receiving at least two other antiglaucoma medications.
      Intraocular pressure was measured at baseline and after treatment for at least 1
      month. All intraocular pressure measurements were taken within 24 hours of drug
      instillation. RESULTS: Six eyes of six patients received latanoprost. Two (28%)
      of the six eyes demonstrated an intraocular pressure decrease that averaged 8.8
      mm Hg. These two responders had juvenile onset glaucoma, whereas the four
      nonresponders had congenital onset glaucoma. CONCLUSIONS: Latanoprost may
      significantly reduce intraocular pressure in selected patients with glaucoma
      associated with Sturge-Weber syndrome.

PMID- 9780112
TI  - Cystoid macular edema associated with latanoprost in aphakic and pseudophakic
      eyes.
AB  - PURPOSE: To describe four patients who developed cystoid macular edema shortly
      after onset of treatment with latanoprost. METHOD: Retrospective review of
      medical records of patients with open-angle glaucoma who developed cystoid
      macular edema shortly after starting latanoprost. RESULTS: The use of topical
      latanoprost was temporally related to the development of cystoid macular edema in
      four patients (six eyes; two aphakic eyes and four pseudophakic eyes). Cystoid
      macular edema resolved in all patients after latanoprost was discontinued.
      CONCLUSIONS: Cystoid macular edema is a potential complication of latanoprost
      therapy. Further observations are needed to determine if the risk of cystoid
      macular edema is limited to or greatest in patients who are pseudophakic or
      aphakic.

PMID- 9780113
TI  - Indocyanine green angiography in enlarged blind spot syndrome.
AB  - PURPOSE: To report the indocyanine green angiography findings in a case of acute
      idiopathic blind spot enlargement syndrome. METHOD: The patient underwent
      ophthalmologic examination with fluorescein angiography and indocyanine green
      angiography. RESULTS: A monocular enlarged blind spot was found on automated
      perimetry; fluorescein angiography showed a hypofluorescent peripapillary
      atrophic area and indocyanine green angiography highlighted diffuse, small
      hypofluorescent spots scattered throughout the posterior pole. Visual field
      defects and indocyanine green angiography abnormalities resolved over 4 weeks.
      CONCLUSION: Indocyanine green angiography in acute idiopathic blind spot
      enlargement syndrome showed many lesions not visible with fluorescein
      angiography, indicating a choroidal involvement reaching not only the
      peripapillary area but the entire posterior pole.

PMID- 9780114
TI  - Cyclosporine-induced optic neuropathy, ophthalmoplegia, and nystagmus in a
      patient with Crohn disease.
AB  - PURPOSE: To report the cyclosporine-induced complications of optic neuropathy,
      partial external ophthalmoplegia, and other neurologic abnormalities. METHODS:
      Case report. A 22-year-old man with severe active Crohn disease developed
      bilateral optic neuropathy, nystagmus, external ophthalmoplegia, and ataxia on
      the fifth day of cyclosporine A (CyA) parenteral therapy. RESULTS: Cyclosporine
      therapy was discontinued as soon as toxic clinical manifestations appeared.
      Cyclosporine blood level detected then was 1,290 ng/ml (therapeutic level: 150 to
      300 ng/ml). Partial external ophthalmoplegia improved dramatically; however, the
      patient's optic neuropathy progressed to optic atrophy, leaving the patient
      visually impaired. Various possible mechanisms for cyclosporine-induced
      neurotoxicity are discussed. CONCLUSION: It is important to closely monitor neuro
      ophthalmologic and neurologic signs of patients treated with cyclosporine.

PMID- 9780115
TI  - Radiation-associated cerebral blindness.
AB  - PURPOSE: To report a case of blindness caused by a white-matter injury after
      whole brain irradiation for metastatic renal cell carcinoma. METHODS: Case
      report. We performed comprehensive serial neuro-ophthalmologic examinations.
      RESULTS: Four to 5 months after resection of renal cell metastasis in the left
      occipital cortex, interleukin-2 therapy, and whole brain irradiation with 3,000
      cGy plus a 1,500-cGy boost to the posterior third of the brain, the patient
      developed a progressive decline in visual acuity in both eyes to hand motions.
      Magnetic resonance imaging disclosed signal abnormalities without mass effect in
      the white matter of the parietal and occipital lobes bilaterally, including the
      optic radiations. CONCLUSION: This case is a unique example of cortical blindness
      secondary to radiation injury in the occipital lobes and optic radiations.

PMID- 9780116
TI  - Liquefied aftercataract: a complication of continuous curvilinear capsulorhexis
      and intraocular lens implantation in the lens capsule.

PMID- 9780117
TI  - Pharmacodynamic monitoring of cancer chemotherapy: childhood acute lymphoblastic
      leukemia as a model.
AB  - Childhood acute lymphoblastic leukemia (ALL) has long served as a model of
      disseminated cancer that can be cured with chemotherapy. Although pharmacokinetic
      variability has been shown to influence the efficacy of ALL chemotherapy, the
      usefulness of conventional pharmacokinetic measures to predict responses to
      individual chemotherapeutic agents can be confounded in the context of multiagent
      chemotherapy. This has led to the concomitant use of pharmacodynamic endpoints to
      identify patients who exhibit a poor initial response to therapy or whose
      residual disease has a persistence that predicts a poor prognosis unless therapy
      is changed. To this end, the initial reduction of leukemia cells in peripheral
      blood or in bone marrow and the detection of minimal residual disease by
      immunologic or polymerase chain reaction-based methods have shown promise as
      pharmacodynamic endpoints to identify patients who are at high risk for relapse
      if therapy remains unchanged. Prospective clinical trials are needed to determine
      the clinical usefulness of pharmacodynamic monitoring and to define more
      precisely the integration of pharmacokinetic and pharmacodynamic monitoring to
      optimize the treatment of childhood ALL.

PMID- 9780118
TI  - The monitoring of immunosuppressive drugs: a pharmacodynamic approach.
AB  - Pharmacodynamic monitoring measures biologic response to a drug, which, alone or
      coupled with pharmacokinetics, provides a novel method for the optimization of
      drug dosing. Pharmacodynamic monitoring has been investigated by us and other
      investigators on primarily five immunosuppressive drugs: cyclosporine (CsA),
      mycophenolate mofetil (MMF), rapamycin (RAPA), azathioprine (AZA), and
      methylprednisolone (MP). The pharmacodynamic monitoring of CsA and MMF involves
      measurement of the activity of the enzymes calcineurin and inosine monophosphate
      dehydrogenase, respectively. The pharmacodynamics of AZA are assessed by
      measurement of the activity of thiopurine methyl transferase (TPMT), which is
      induced by a metabolite of AZA, 6-mercaptopurine. The pharmacodyamics for RAPA
      involve the measurement of a P70 S6 kinase activity within lymphocytes, whereas
      that for MP involves the measurement of the endogenous synthesis of cortisol by
      the suppression of the hypothalamic pituitary axis. To date, the most detailed
      studies have been performed involving pharmacodynamic monitoring of CsA and MMF.
      Similarities exist in the pharmacodynamic response to CsA and MMF in patients who
      undergo renal transplantation. At trough concentrations in blood, both drugs
      result in only a 50% reduction in activity of their target enzymes; however,
      there is considerable interpatient variability. Throughout the dosing interval,
      enzyme activity parallels that of drug concentrations. Renal transplant
      recipients who are treated with AZA and who exhibit an increase in TPMT activity
      from the time of transplantation experience fewer episodes of active rejection.
      Renal transplant recipients who are administered MP and in whom suppression of
      endogenous synthesis of cortisol is greatest exhibit the least incidence of
      steroid-induced side effects. Additional clinical trials relating
      pharmacokinetics and pharmacodynamic parameters to clinical response are under
      way to ascertain which provides the best guide for dosing. Pharmacodynamic
      monitoring may provide an alternative approach to traditional drug level
      measurement.

PMID- 9780119
TI  - Assays for therapeutic monitoring and pharmacokinetic investigations of
      aminoglycosides: quality aspects.
AB  - Clinical laboratory investigations used to aid antimicrobial chemotherapy of
      serious infection include routine sensitivity testing and, in the case of those
      drugs with a narrow therapeutic range, routine assays for therapeutic monitoring
      to assist with dosage individualization. Tests must be of a sufficiently high
      quality to be clinically useful. Laboratories ensure quality through standard
      operating procedures, internal quality control procedures, and participation in
      external quality assessment (EQA) programs. This article demonstrates how EQA
      returns to the United Kingdom National External Quality Assessment Scheme for
      Antibiotic Assays and the activity of the United Kingdom National Quality
      Assurance Advisory Panel showed marked improvement in the technical quality of
      assays as exemplified by gentamicin assays. The article also highlights
      additional quality concerns not subject to EQA.

PMID- 9780120
TI  - Therapeutic drug monitoring in antituberculosis chemotherapy.
AB  - Therapeutic drug monitoring in antituberculosis chemotherapy may play a strategic
      role in improving outcomes in selected patients. The most important use is in
      assisting clinicians to optimize therapy to achieve success and minimize
      toxicity. The other principal indication lies in the management of interaction of
      antituberculosis drugs with other drugs.

PMID- 9780121
TI  - Pharmacodynamics, pharmacokinetics, and therapeutic drug monitoring of
      glycopeptides.
AB  - The glycopeptide antibacterial drugs, vancomycin and teicoplanin, are widely used
      in hospitals for therapy of severe or multiresistant infection that has a
      positive results on Gram's stain test. Although vancomycin resistance is common
      in some hospital-acquired Enterococcus sp and resistance to teicoplanin occurs
      among Staphylococci sp glycopeptides remain the cornerstone of therapy for
      infection due to methicillin-resistant Staphylococcus aureus (MRSA), coagulase
      negative Staphylococcus organisms, and infection related to implanted devices.
      Therapeutic drug monitoring (TDM) of these agents remains controversial, but
      advances in our understanding of their pharmacodynamics and further clinical
      studies are helping clarify the situation. In the future, a more rational
      approach to monitoring will probably result in less intensive monitoring of
      vancomycin but more intensive monitoring of teicoplanin.

PMID- 9780122
TI  - Diagnosing intrauterine exposure to cocaine by hair testing: six years of
      clinical use.
AB  - Intrauterine exposure to cocaine results in a variety of perinatal and long-term
      neurobehavioral sequlae. Maternal history and neonatal urinalysis miss most
      instances of exposure. After establishing the high sensitivity, specificity, and
      predictive value of neonatal hair testing for cocaine, the authors embarked on a
      study to evaluate the clinical use of the test. Between October 1991 and
      September 1997, they assessed the presence of cocaine in 509 hair samples; 422
      were from neonates and were based on clinical suspicion of intrauterine exposure,
      although history and urine test results were negative. Thirty-two percent were
      positive, a rate fivefold higher than the incidence found by the authors in
      population-based studies. Neonates referred by children's aid workers had
      significantly higher percentages of positivity (60%). Because neonatal hair grows
      only during the last 4 months of pregnancy, positive neonatal hair test results
      reflect maternal addiction, and this warrants close follow-up of the baby after
      release because of the high rate of postnatal risks secondary to suboptimal
      parental care and because of the proven perinatal risks inflicted by the drug
      itself.

PMID- 9780124
TI  - Laboratory support for the poisoned patient.
AB  - Poisoning often does not require toxicology laboratory analysis, though support
      is necessary from the departments of hematology and biochemistry. There are some
      compounds, such as paracetamol (acetaminophen), lithium, and methanol, for which
      quantitative or qualitative analysis is essential for effective patient
      management. Standard methods such as immunoassays, chromatography, and
      spectrophotometry have been extended by mass spectrometry and will be enhanced by
      nuclear magnetic resonance and by hyphenated techniques (e.g., LC-MS-MS). The new
      perspectives that can be gained with these techniques may greatly improve our
      knowledge of toxicokinetics and enable better patient management. Comatose
      patients and those with suspected brain death comprise a difficult group
      requiring comprehensive toxicologic screens. Although current immunoassay
      chromatography methods are adequate, it is to be hoped that more comprehensive
      screens are achievable. The author has performed trials on TLC-FABMS-MS as a
      potential procedure and has obtained satisfactory preliminary results. This and
      other spectrometric-spectroscopic methods may be the techniques of the future for
      reference centers.

PMID- 9780123
TI  - Use and abuse of the benzodiazepines.
AB  - Since chlordiazepoxide was introduced in 1961, the benzodiazepines have had many
      important roles in the pharmacotherapy of various disorders. This drug class for
      the central nervous system has been considered one of the safest in use for 35
      years, especially when the benzodiazepines are compared with the barbiturates
      they often replaced. The objective of this article is to provide an update on the
      availability and distribution of benzodiazepines around the world and to discuss
      their most common clinical applications. Adverse effects of benzodiazepines,
      observed after long-term therapeutic use and after overdoses, are also presented.
      Triazolam is discussed because this benzodiazepine was removed from the market by
      regulatory authorities in the United Kingdom in 1991. Benzodiazepines will
      continue to have an important role in clinical medicine. Their clinical use,
      however, should be monitored more closely because of the greater awareness of
      their adverse effects after long-term use and because of the potential for misuse
      and abuse.

PMID- 9780125
TI  - Practical management of the poisoned patient.
AB  - Clinical toxicology is undergoing a change in its previously perceived
      unscientific image. As in other medical disciplines, there is an effort to ensure
      that its treatments are evidence based. A successful outcome seems likely not
      only to rationalize the management of poisoned patients but to simplify it.

PMID- 9780126
TI  - Environmental poisoning: presentation and management.
AB  - Environmental poisoning is most commonly associated with chronic long-term
      exposure to toxins rather than to acute exposure. Such repeated exposure to
      sublethal doses of compounds and elements presents problems in risk assessment.
      This is primarily because the data are unavailable to describe relationships
      between dose and effect at lower levels of exposure to toxins. Bioavailability of
      toxins also presents a problem because the data on bioavailability are sparse and
      seldom as high as the default of 100% bioavailability commonly used in risk
      assessment. Examples are presented of two toxins: arsenic as an elemental
      anthropogenic and geologic poison and ciguatoxin, a polyether ladder compound, as
      a toxin produced naturally by dinoflagellates. Bioavailability drives the
      toxicity of arsenic from contaminated sites, whereas tissue accumulation drives
      the toxicity of ciguatoxin. Considerable benefit is derived from the
      harmonization of regulatory processes where there is linkage of health and
      environmental factors in the derivation of credible risk assessment.

PMID- 9780127
TI  - The toxicology of African herbal remedies.
AB  - Toxicity related to traditional medicines is becoming more widely recognized as
      these remedies become popular in developed countries. Accidental herbal toxicity
      occurs not only as a result of a lack of pharmaceutic quality control in
      harvesting and preparation but also because herbal remedies are believed to be
      harmless. Although there is a huge amount of data available documenting the
      pharmacologically active ingredients of many plants, it is seldom helpful to the
      toxicologist in an acute situation. Current analytic methods such as high
      performance liquid chromatography, gas chromatography--mass spectrometry, and
      immunoassays can provide identification of the toxin in those few cases in which
      the history or symptoms give a clear lead, but broad screening methods remain to
      be developed. In most cases of plant poisoning, treatment continues to be only of
      symptoms, with few specific antidotes available. It is important that
      toxicologists in the West be alert to the possibility of encountering poisoning
      in patients due to traditional African remedies.

PMID- 9780128
TI  - Genetic determinants of drug responsiveness and drug interactions.
AB  - Six cytochrome P450 enzymes mediate the oxidative metabolism of most drugs in
      common use: CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4. These enzymes
      have selective substrate specificity, and their activity is characterized by
      marked interindividual variation. Some of these systems (CYP2C19, CYP2D6) are
      polymorphically distributed; thus, a subset of the population may be genetically
      deficient in enzyme activity. Phenotyping procedures designed to identify
      subjects with impaired metabolism who may be at increased risk for drug toxicity
      have been developed and validated. This has been supplemented in recent years by
      the availability of genetic analysis and the identification of specific alleles
      that are associated with altered (i.e., reduced, deficient, or increased) enzyme
      activity. The potential of genotyping to predict pharmacodynamics holds great
      promise for the future because it does not involve the administration of
      exogenous compound and is not confounded by drug therapy. Drug interactions
      caused by the inhibition or induction of oxidative drug metabolism may be of
      great clinical importance because they may result in drug toxicity or therapeutic
      failure. Further understanding of cytochrome P450 complexity may allow, through a
      combined in vitro-in vivo approach, the reliable prediction and possible
      prevention of deleterious drug interactions.

PMID- 9780129
TI  - Ethnic differences in drug disposition and response.
AB  - Interindividual variability in drug response is a well-recognized problem
      resulting in both undertreatment and overtreatment of individuals receiving
      similar doses of drugs, with the potential for lack of therapeutic effect and for
      drug toxicity. The potential that interethnic differences might contribute to
      such interindividual variability in drug response has recently been recognized.
      Such interethnic differences in drug response may be due to either altered drug
      disposition or altered drug sensitivity among races at similar drug
      concentrations. In turn, such racial differences in drug disposition may be
      related to genetic or environmental factors, which are often difficult to
      separate.

PMID- 9780130
TI  - Clinical implications of thiopurine methyltransferase--optimization of drug
      dosage and potential drug interactions.
AB  - Thiopurine methyltransferase (TPMT) is a cytoplasmic enzyme that preferentially
      catalyzes the S-methylation of aromatic and heterocyclic sulphydryl compounds,
      such as the thiopurine drugs azathioprine, mercaptopurine, and thioguanine. These
      drugs form the same terminal metabolites, the thioguanine nucleotides (TGNs). One
      major influence on thiopurine therapy is the inherited activity of TPMT. TPMT
      "deficiency" is associated with grossly elevated TGN concentrations and profound
      toxicity after a short course of thiopurine therapy. Variant alleles producing a
      functional loss of TPMT activity have now been described. Although all the ethnic
      groups investigated to date have the same wild-type enzyme, TPMT variant allele
      frequencies vary. Potentially, TPMT activity can influence a number of compounds
      that could be coadministered with thiopurine drugs. After a therapeutic dose of
      aspirin, plasma concentrations of salicylic acid are within the range for TPMT
      inhibition. Sulfasalazine and its metabolite 5-aminosalicylic acid inhibit TPMT,
      and concurrent furosemide therapy could influence the S-methylation of
      thiopurines. In addition, TPMT could interfere with disulfiram treatment in
      alcoholism. TPMT S-methylates the diethyldithiocarbamate metabolite involved in
      disulfiram activation.

PMID- 9780131
TI  - Clinical assessment of DNA analysis for toxicology.
AB  - The impact of discoveries in biotechnology-particularly those dealing with DNA-
      will be among the most significant factors changing the world in the next decade.
      Toxicologists will not escape this change; they, too, will be significantly
      impacted by the new genetics.

PMID- 9780132
TI  - Economic and outcome issues for therapeutic drug monitoring in medicine.
AB  - Outcome and economic studies pertaining to the use of therapeutic drug monitoring
      (TDM) are summarized. The studies were classified by a 2 x 2 matrix comprised of
      process, outcome, system-related variables, and patient-centered variables. Two
      hundred forty-seven studies conducted from 1974 to 1994, culled from eight
      summary sources, were reviewed. Almost 75% of the studies reported system
      related, not patient-centered, measures for assessing the value of TDM; nearly
      the same percentage evaluated processes as opposed to outcome measures. Studies
      comparing TDM to non-TDM populations generally showed that TDM as an intervention
      reduced the rate of undesirable system-related variables by 50% and increased the
      rate of desirable system-related variables by 100%. For patient-centered
      variables, TDM was less dramatic, decreasing the rate of undesirable variables by
      15% to 50%. Only 8% of the studies examined economic variables. TDM-influenced
      changes in process variables resulted in a projected mean annual savings of
      $37,000. The few studies available of cost-benefit analysis focused on
      aminoglycosides and showed that TDM yielded a range from 4:1 to 52:1 in benefit
      to-cost ratio. Most studies have limitations that include small sample size,
      short study periods to predict long-term outcomes, no long-term follow-up, and
      designs for noncontrolled study.

PMID- 9780133
TI  - Therapeutic monitoring of busulfan in hematopoietic stem cell transplantation.
AB  - Busulfan is an alkylating agent commonly used to ablate marrow before
      hematopoietic stem cell transplantation. High levels have been shown to increase
      the chance for severe hepatic veno-occlusive disease, for which there is no
      treatment and which can be fatal. Low levels are associated with recurrence of
      chronic myeloid leukemia, whereas even lower levels are associated with graft
      rejection. The therapeutic window for busulfan is narrow and disease and graft
      source dependent. Busulfan concentration in plasma is readily assayed by gas
      chromatography. In the authors' center, busulfan levels determined from the first
      dose of the drug are used to adjust the dose to that selected to achieve the
      desired therapeutic outcome by the third dose of the 16-dose regimen. Thus,
      turnaround time is less than 6 hours. Analytical and pharmacokinetic aspects of
      busulfan therapeutic monitoring are described. The cost of pharmacokinetically
      targeting busulfan concentration is < or = 1% of the cost of hematopoietic stem
      cell transplantation.

PMID- 9780134
TI  - Improving the use of therapeutic drug monitoring.
AB  - Many studies suggest that therapeutic drug monitoring (TDM) could be used better.
      For example, a high proportion of TDM assays either lack an inappropriate
      indication or are drawn with suboptimal timing, particularly for inpatients. From
      a perspective of quality, undermonitoring has more potential adverse consequences
      than overmonitoring. Because both overuse and underuse occur, it may be possible
      to improve the quality of TDM while reducing its costs and, more important, to
      have similar effects on the quality and costs associated with caring for patients
      administered drugs.

PMID- 9780135
TI  - Cocaine metabolism and urinary excretion after different routes of
      administration.
AB  - Cocaine abusers frequently self-administer cocaine by different routes of
      administration. A controlled-dosing study was performed to assess the effect of
      different routes of administration on the excretion profile of cocaine and
      metabolites in urine. Single bioequivalent doses of cocaine were administered by
      the intravenous, intranasal, and smoked routes to six human subjects. Urine
      specimens were collected for 3 days after drug administration and were analyzed
      for cocaine, metabolites, and anhydroecgonine methyl ester, the thermal
      degradation product of cocaine, by gas chromatography-mass spectrometry. Cocaine
      was rapidly absorbed, metabolized, and excreted in urine. Peak cocaine
      concentrations were generally present in the first specimen collected;
      thereafter, concentrations declined quickly and were usually below the limit of
      detection (approximately 1 ng/ml) within 24 hours. The metabolite benzoylecgonine
      was present in the highest concentration and represented approximately 39%, 30%,
      and 16%, of the administered dose by the intravenous, intranasal, and smoked
      routes, respectively. Combined amounts of ecgonine methyl ester and six minor
      metabolites (norcocaine, benzoylnorecgonine, m-hydroxycocaine, p-hydroxycocaine,
      m-hydroxybenzoylecgonine, and p-hydroxybenzoylecgonine) accounted for
      approximately 18%, 15%, and 8% of the administered dose by the intravenous,
      intranasal, and smoked routes, respectively. Anhydroecgonine methyl ester was
      present in trace amounts (0.02% dose) in specimens collected after smoked cocaine
      administration. Because many of these metabolites exhibit pharmacologic activity,
      their presence in urine may indicate that they play complex biologic roles in the
      overall activity of cocaine.

PMID- 9780136
TI  - Formation and clearance of active and inactive metabolites of opiates in humans.
AB  - The results of recent investigations of the analgesic and the nonanalgesic
      effects of opioid glucuronides are relevant to the research on drug abuse in
      forensic toxicology. As has been shown for heroin, knowledge of the state of
      distribution and elimination of active and inactive metabolites and glucuronides
      offers new possibilities in forensic interpretation of analytic results. Because
      of similar metabolic degradation, calculation of the time-dependent ratio of the
      concentration of morphine and its glucuronide metabolites in blood or serum
      allows a rough estimation of increased dosage and of time elapsed since the last
      application. Drug effects can be examined with respect to individual case
      histories, including overdose and survival time if the patient died. However,
      different methods of administration and the strong influence of different volumes
      or compartments of distribution of parent compounds and metabolites on
      concentrations in human body tissues require careful use of glucuronide
      concentration data. In Germany, dihydrocodeine (DHC) is prescribed as a heroin
      substitute, and relative overdoses are needed to be effective. DHC metabolism was
      studied in three patients who died from overdoses. All metabolites
      (dihydrocodeine-6-glucuronide [DHC6], nor-DHC [NDHC], dihydromorphine [DHM], nor
      DHM [NDHM], and DHM-3- and 6-glucuronide [DHM3G, DHM6G]) were determined using
      HPLC and fluorescence detection. Concentrations of DHM (0.16 mg/L to 0.22 mg/L
      serum) were found. The DHM glucuronide ratios were similar to those of morphine.
      Receptor binding studies showed that the binding affinity of DHM to porcine mu
      receptor was higher than that of morphine, and DHM6G's binding affinity was as
      high as that of morphine-6-glucuronide (M6G). Metabolites may play an important
      role in the effectiveness of DHC in substitution and toxicity. Because of enzyme
      polymorphism, the formation of DHC poses a risk for proper dosage in patients who
      are either poor or extensive metabolizers. The distribution of opioid
      glucuronides in cerebral spinal fluid in relation to transcellular transport in
      central nervous tissue is discussed with respect to the receptor binding of
      opiates and drug effect.

PMID- 9780137
TI  - Urinary excretion half-life of 11-nor-9-carboxy-delta9-tetrahydrocannabinol in
      humans.
AB  - The excretion of marijuana metabolites occurs over an extended period of time,
      yet few studies have been designed for accurate estimation of excretion half
      lives. The authors monitored excretion of the primary urinary metabolite of
      marijuana, 11-nor-9-carboxy-delta9-tetrahydrocannabinol (THCCOOH), by gas
      chromatography-mass spectrometry in a controlled clinical study of marijuana
      smoking that included measurement of the drug in each urine void collected during
      the 3-week study. Terminal excretion half-lives of THCCOOH were determined in six
      healthy male subjects with histories of marijuana smoking; the study was
      conducted on the clinical research unit of a major medical institution. Subjects
      smoked a single marijuana cigarette (placebo, 1.75% or 3.55% THC) each week.
      Urine specimens (N=953) were analyzed under blind conditions for THCCOOH by gas
      chromatography-mass spectrometry. Mean+/-SEM half-lives calculated by the amount
      remaining to be excreted method after the low and high doses were 31.5+/-1.0
      hours (range, 28.4 to 35.3 hours) and 28.6+/-1.5 hours (range, 24.9 to 34.5
      hours), respectively, when a 7-day monitoring period was used. The amounts of
      THCCOOH excreted over a 7-day period were 93.9 +/-24.5 microg (range, 34.6 to
      171.6 microg) and 197.4+/-33.6 microg after the low- and high-dose sessions.
      Longer half-lives, 44.3 to 59.9 hours, were obtained with a 14-day sample
      collection. This study documents the prolonged excretion of THCCOOH in urine and
      emphasizes the importance of study design in the precise estimation of terminal
      excretion half-lives. A sensitive analytical method and a prolonged specimen
      collection period are important study considerations in the monitoring of
      marijuana excretion.

PMID- 9780138
TI  - Therapeutic approach to drug resistant tumors.
AB  - Drug resistance is a major problem in cancer chemotherapy. P-glycoprotein plays a
      major role in multidrug resistance in cancer cells. P-glycoprotein is expressed
      in some normal tissues and has physiological functions. These include protecting
      the brain against toxic substances at the blood-brain barrier site, excreting
      toxic substances from the liver, kidney, and gastrointestinal tracts, and
      transporting steroidal hormones in the adrenal grand. Once expressed in cancer
      cells. P-glycoprotein effluxes a variety of anticancer drugs, such as
      doxorubicin, vinca alkaloids, etoposide and taxol, and thereby allows cancer
      cells to show resistance to these drugs.

PMID- 9780139
TI  - Resistance to anticancer drugs: are we ready to use biologic information for the
      treatment of patients with cancer?
AB  - Multidrug resistance (MDR) to anticancer drugs can be diagnosed in tumors by
      molecular biology techniques (expression of the MDR1 gene), by immunologic
      techniques (expression of P-glycoprotein), and by functional approaches (dye
      exclusion). Numerous studies have tried to correlate the MDR status of tumors to
      the clinical response to the treatment, but wide discrepancies prevented
      definitive conclusions. As a consequence, the routine use of these techniques is
      still not possible, and continuous efforts are needed for their standardization.
      The development of MDR modulators in the clinical setting is a promising approach
      that requires rigorous clinical trials, especially with sequential design of
      phase 2 protocols. Definitive results are still lacking concerning the interest
      of combining an MDR modulator to standard chemotherapy for resistant cancers.

PMID- 9780140
TI  - P-glycoprotein-mediated efflux transport of anticancer drugs at the blood-brain
      barrier.
AB  - Several lipophilic, cytotoxic drugs, or both, (including anticancer drugs [Vinca
      alkaloids, doxorubicin, cyclosporin A, and digoxin]) have proven to be actively
      effluxed by P-glycoprotein (P-gp) expressed at the luminal membrane of the brain
      capillary endothelial cells, resulting in the very low apparent blood-brain
      barrier (BBB) permeation of these P-gp substrates from the blood circulating to
      the brain. In rats inoculated with 9L-glioma cells into the brain, the
      endothelial cells of tumor-associated vessels allowed easy penetration of
      anticancer drugs (ranimustine and doxorubicin) in tumor regions, although the
      normal BBB function still operated at the normal brain region to provide a
      barrier to the accumulation of P-gp substrates. A detailed knowledge of the BBB
      function would be very helpful in developing improved delivery systems of
      anticancer drugs to brain tumors.

PMID- 9780141
TI  - Presence of progenitors restricted to T, B, or myeloid lineage, but absence of
      multipotent stem cells, in the murine fetal thymus.
AB  - The most immature population of fetal thymus (FT) cells has been shown to
      generate not only T but also B and myeloid cells. The present study was
      undertaken to clarify whether such a multipotent activity of the earliest
      population of FT cells is attributed to multipotent hemopoietic progenitors or to
      a mixture of lineage-restricted progenitors. Examination of individual FT
      progenitors by a recently established clonal assay system, which is able to
      determine the developmental potential of each progenitor toward T, B, and myeloid
      lineages, elucidated that a large majority of progenitors in FT were restricted
      to the T cell lineage. Presence of a small number of B or myeloid lineage
      restricted progenitors was also disclosed. No multipotent progenitors, however,
      were detected in FT. These results are consistent with our recent finding that
      restriction of hemopoietic stem cells to T, B, and myeloid lineages takes place
      in the fetal liver.

PMID- 9780142
TI  - Negative regulation of human T cell activation by the receptor-type protein
      tyrosine phosphatase CD148.
AB  - T cell activation represents a balance between positive and negative signals
      delivered via distinct cell surface molecules. Many cytoplasmic protein tyrosine
      phosphatases are involved in regulating cellular responses by antagonizing the
      action of protein tyrosine kinases. CD148 is a receptor-type protein tyrosine
      phosphatase expressed by all human mononuclear cells. We have investigated the
      effect of CD148 on TCR-mediated activation of human T cells. Overexpression of
      wild-type, but not a phosphatase-deficient, CD148 in Jurkat T cells inhibited TCR
      mediated activation, evidenced by reduced expression of the early activation Ag
      CD69, inhibition of tyrosine phosphorylation of many intracellular proteins
      including the critical protein tyrosine kinase ZAP-70, and impairment of mitogen
      activated protein kinase activation. Taken together, these results suggest that
      CD148 is an important phosphatase involved in negatively regulating the proximal
      signaling events during activation of Ag-specific T cells.

PMID- 9780143
TI  - Cross-priming of CTL responses in vivo does not require antigenic peptides in the
      endoplasmic reticulum of immunizing cells.
AB  - It has been proposed that the cross-priming of CTL responses in vivo involves the
      transfer to host APCs of heat shock protein glycoprotein 96-chaperoned antigenic
      peptides released from the endoplasmic reticulum (ER) of dying or infected cells.
      We have tested this possibility directly using TAP-deficient cell lines lacking
      antigenic ER peptides derived from two model Ags, the human adenovirus type 5
      early regions E1A and E1B. Although both proteins were well expressed, the cells
      were not recognized by E1A- or E1B-specific CTLs unless the relevant epitope was
      either provided exogenously as a synthetic peptide or targeted to the ER in a TAP
      independent fashion. Despite the absence of these ER peptides, the TAP1-/- cells
      were able to efficiently cross-prime E1A- and E1B-specific CTLs following
      immunization of syngeneic mice. These results indicate that, although purified
      peptide/glycoprotein 96 complexes are potent immunogens, the mechanism of CTL
      cross-priming in vivo does not depend upon antigenic peptides in the ER of
      immunizing cells.

PMID- 9780144
TI  - IL-4-independent induction of airway hyperresponsiveness by Th2, but not Th1,
      cells.
AB  - We investigated the role of Th1 or Th2 cells in airway hyperresponsiveness (AHR),
      because both IFN-gamma and IL-4 and IL-5-producing CD4 T cells have been
      identified in the airways of asthmatics. After transfer of in vitro-generated TCR
      transgenic Th1 or Th2 cells and exposure to inhaled Ag, Th2 cells induced AHR and
      airway eosinophilia, whereas Th1 cells induced neutrophilic inflammation without
      AHR. Next, to determine the precise effector function of IL-4 in Th2 cell-induced
      AHR, we transferred IL-4(-/-) Th2 cells into wild-type and IL-4(-/-) recipient
      mice. After exposure to inhaled Ag, both groups of mice exhibited AHR with
      markedly reduced airway eosinophilia. Thus, IL-4 production by Th2 cells is not
      essential for the induction of AHR, but is critical for the migration of
      eosinophils from lung tissue into the airways.

PMID- 9780145
TI  - Differential responsiveness of the IL-5 and IL-4 genes to transcription factor
      GATA-3.
AB  - The cytokines IL-4 and IL-5 are often coordinately produced by Th2 cells as in
      asthma. However, it is unclear whether similar molecular mechanisms underlie
      transcription of the two genes. We have previously shown that the transcription
      factor GATA-3 is expressed in Th2 but not Th1 cells and is crucial for activation
      of the IL-5 promoter by different stimuli. In a different study, GATA-3 was shown
      to be sufficient for the expression of IL-4 and other Th2 cytokine genes. Here,
      we show that ectopic expression of GATA-3 is sufficient to drive IL-5 but not IL
      4 gene expression. Also, in Th2 cells, antisense GATA-3 RNA inhibits IL-5 but not
      IL-4 promoter activation. The induction of IL-5 gene expression by GATA-3
      involves high affinity binding of GATA-3 to an inverted GATA repeat in the IL-5
      promoter.

PMID- 9780146
TI  - GATA-3-dependent enhancer activity in IL-4 gene regulation.
AB  - Previously, we analyzed the proximal IL-4 promoter in directing Th2-specific
      activity. An 800-base pair proximal promoter conferred some Th2-selective
      expression in transgenic mice. However, this region directed extremely low
      reporter mRNA levels relative to endogenous IL-4 mRNA, suggesting that full gene
      activity requires additional enhancer elements. Here, we analyzed large genomic
      IL-4 regions for enhancer activity and interaction with transcription factors.
      The proximal IL-4 promoter is only moderately augmented by GATA-3, but certain
      genomic regions significantly enhanced GATA-3 promoter transactivation. Some
      enhancing regions contained consensus, GATA sites that bound Th2-specific
      complexes. However, retroviral transduction of GATA-3 into developing T cells
      induced IL-5 to full Th2 levels, but only partially restored IL-4 production.
      Thus, we propose that GATA-3 is permissive, but not sufficient, for full IL-4
      enhancement and may act through GATA elements surrounding the IL-13/IL-4 gene
      locus.

PMID- 9780147
TI  - Qualitative and quantitative effects of CD28/B7-mediated costimulation on naive T
      cells in vitro.
AB  - The CD28/B7 system provides costimulatory signals necessary for optimal T cell
      activation. We have examined the effects of blocking B7.1 and/or B7.2 in an in
      vitro system using TCR transgenic T cells specific for myelin basic protein.
      Activation of naive T cells was found to be B7.2 dependent and not dependent on
      the presence of B7.1 molecules. However, increasing the strength of signal
      through the TCR using peptide analogues with higher affinity for MHC compensated
      for blockade of B7.2 molecules, suggesting that signal 1 alone can be sufficient
      for the activation of naive T cells. The role of B7 molecules in the
      differentiation of T cells was further investigated by restimulating T cells with
      fresh APC and peptide in B7-sufficient conditions. A down-regulation of IL-2 and
      IFN-gamma production by T cells primed in the presence of anti-B7.2 mAb was
      partially overcome when high affinity peptide analogues were used to restimulate
      T cells. In contrast, a significant down-regulation of the differentiation of
      cells producing Th-2 cytokines was observed in the presence of anti-B7 Abs.
      Differentiation of IL-4-secreting cells was influenced by both B7.1 and B7.2,
      while IL-5 secretion was totally dependent on B7.2. These results suggest that B7
      mediated costimulation is essential for the development of Th-2-associated
      cytokines, the absence of which cannot be overcome by increasing the strength of
      the signal through the TCR.

PMID- 9780148
TI  - Transfer of primitive stem/progenitor bone marrow cells from LT alpha-/- donors
      to wild-type hosts: implications for the generation of architectural events in
      lymphoid B cell domains.
AB  - To analyze whether the phenotypic abnormalities observed in lymphotoxin-alpha(-/
      ) (LT alpha-/-) mice are intrinsic to the hemolymphoid system itself or dependent
      on stromal elements, wild-type (WT) mice were reconstituted with bone marrow (BM)
      cells enriched for hemopoietic stem cells from LT alpha-/- animals. WT mice
      reconstituted with LT alpha-/- c-kit+ Lin- Sca-1+ BM cells do not maintain
      follicular dendritic cell (FDC) networks and do not form primary follicles, while
      clear segregation of B and T cells could be observed. Furthermore, IgM+ IgD- B
      cells, MOMA-1 (anti-metallophilic macrophages), ERTR-9 (anti-marginal zone
      macrophages), and MECA-367 (anti-MAdCAM-1) were all absent from the splenic
      marginal zone. Surprisingly, however, the expression of MOMA-1, ERTR-9, and
      MAdCAM-1 was normal in the lymph nodes of mice reconstituted with LT alpha-/-
      cells. In addition, peanut agglutinin-positive germinal centers were observed in
      both the spleen and mesenteric lymph nodes, although in the absence of detectable
      FDC. Furthermore, in animals reconstituted with a mixture of LT alpha-/- and WT c
      kit+ Lin- Sca-1+, GC contained either predominantly LT alpha-/- B cells or WT B
      cells. These results suggest that although the formation of primary follicles,
      FDC networks, and the splenic marginal zone are all dependent on hemopoietically
      derived LT alpha, germinal center formation and the expression of MAdCAM-1, MOMA
      1, and ERTR-9 in lymph nodes are not. Our results also suggest that the disturbed
      B-T cell separation in LT alpha-/- mice is unrelated to defects in the marginal
      zone.

PMID- 9780149
TI  - High antigen density and IL-2 are required for generation of CD4 effectors
      secreting Th1 rather than Th0 cytokines.
AB  - We reevaluated the effects of Ag dose on the polarization of CD4 effectors
      generated in vitro from naive pigeon cytochrome c-specific TCR transgenic T cells
      under conditions in which we could eliminate contaminating non-naive CD4 cells
      and the effects of heterogeneous Ag-presenting populations. When the possibility
      of contaminating non-naive T cells was reduced by using T cells from transgenic
      mice on a RAG-2(-/-) background, Ag dose did not have a significant effect in Th1
      and Th2 polarization unless exogenous IL-2 was initially added to cultures.
      Effectors generated were uniformly Th0 but produced only IL-2 in substantial
      amounts. When exogenous IL-2 was added to priming cultures, T cells secreting a
      Th0 phenotype (large quantities of IL-2, IL-4, IL-5, and IFN-gamma) developed,
      except at very high doses of Ag, where there was a striking reduction in IL-4 and
      IL-5 secretion. Our results imply that Ag dose does not have a direct effect on
      Th1/Th2 polarization, except under conditions that include a high level of TCR
      ligation and in the presence of high levels of IL-2, where production of Th2
      cytokines may be down-regulated by a mechanism that is not yet clear.

PMID- 9780151
TI  - Therapy with monoclonal antibodies. II. The contribution of Fc gamma receptor
      binding and the influence of C(H)1 and C(H)3 domains on in vivo effector
      function.
AB  - An in vivo model is used to define Fc motifs engaged by mAbs to deplete target
      cells. Human IgG1 and human IgG4 were very potent, and mutations within a motif
      critical for Fc gammaR binding (glutamate 233 to proline, leucine/phenylalanine
      234 to valine, and leucine 235 to alanine) completely prevented depletion. Mouse
      IgG2b was also potent, and mutations to prevent complement activation did not
      impair depletion with this isotype, as previously shown for human IgG1. In
      contrast, a mutation that impaired binding to mouse Fc gammaRII (glutamate 318 to
      alanine) eliminated effector function of mouse IgG2b and also reduced the potency
      of human IgG4. To reveal potential contributions of domains other than C(H)2,
      domain switch mutants were created between human IgG1 and rat IgG2a. Two hybrid
      mAbs were generated with potencies exceeding anything previously seen in this
      model. While their mechanism of depletion was not defined, their activity
      appeared dependent upon interdomain interactions in the Fc region.

PMID- 9780150
TI  - c-Fos induces apoptosis in germinal center B cells.
AB  - We examined the role of c-Fos in the differentiation of mature B cells into IgG
      producing cells using transgenic mice carrying the c-fos gene under the control
      of the IFN-alpha/beta-inducible Mx promoter (Mx-c-fos) or the constitutive H-2Kb
      promoter (H2-c-fos). Splenic B cells from Mx-c-fos mice were cultured with LPS
      and rIL-4, and IgG1+ B cells were developed in the culture after day 3. When IFN
      alpha/beta was added to the culture from day 2, development of IgG1+ B cells was
      perturbed, and the number of apoptotic cells increased within 24 h, suggesting
      that c-Fos induces apoptosis in Ig class-switching B cells. To confirm the effect
      of c-Fos on B cell differentiation in vivo, H2-c-fos mice were immunized with DNP
      OVA. The mice produced primary IgM, but not IgG, anti-DNP Ab in serum and failed
      to generate germinal centers in spleen. The perturbation of germinal center
      formation in H2-c-fos mice was rescued by mating them with transgenic mice
      carrying the bcl-2 gene with the Ig promoter. However, primary IgG1 anti-DNP Ab
      production was still suppressed in doubly transgenic mice, suggesting that Bcl-2
      can delay the time of c-Fos-induced apoptosis in Ig class-switching B cells but
      cannot rescue the death. Since c-Fos is induced in mature B cells reacted with
      Ags, and clonal deletion of self-reactive B cells in germinal centers is
      insensitive to Bcl-2, these results suggest that c-Fos plays a causal role in
      clonal deletion of germinal center B cells.

PMID- 9780152
TI  - Long-lasting protective immunity to experimental autoimmune encephalomyelitis
      following vaccination with naked DNA encoding C-C chemokines.
AB  - DNA vaccination represents a novel means of expressing Ag in vivo for the
      generation of both humoral and cellular immune responses. The current study uses
      this technology to elicit protective immunity against experimental autoimmune
      encephalomyelitis (EAE), a T cell-mediated autoimmune disease of the central
      nervous system that serves as an experimental model for multiple sclerosis. RT
      PCR verified by Southern blotting and sequencing of PCR products of four
      different C-C chemokines, macrophage-inflammatory protein-1alpha (MIP-1alpha),
      monocyte-chemotactic protein-1 (MCP-1), MIP-1beta, and RANTES, were performed on
      brain samples from EAE rats to evaluate mRNA transcription at different stages of
      disease. Each PCR product was then used as a construct for naked DNA vaccination.
      The subsequent in vivo immune response to MIP-1alpha or MCP-1 DNA vaccines
      prevented EAE, even if disease was induced 2 mo after administration of naked DNA
      vaccines. In contrast, administration of the MIP-1beta naked DNA significantly
      aggravated the disease. Generation of in vivo immune response to RANTES naked DNA
      had no notable effect on EAE. MIP-1alpha, MCP-1, and MIP-1beta mRNA transcription
      in EAE brains peaked at the onset of disease and declined during its remission,
      whereas RANTES transcription increased in EAE brains only following recovery.
      Immunization of CFA without the encephalitogenic epitope did not elicit the anti
      C-C chemokine regulatory response in DNA-vaccinated rats. Thus, modulation of EAE
      with C-C chemokine DNA vaccines is dependent on targeting chemokines that are
      highly transcribed at the site of inflammation at the onset of disease.

PMID- 9780153
TI  - SLP-76 expression is restricted to hemopoietic cells of monocyte, granulocyte,
      and T lymphocyte lineage and is regulated during T cell maturation and
      activation.
AB  - The leukocyte-specific adapter protein SLP-76 is known to augment the
      transcriptional activity of nuclear factor of activated T cells and AP-1
      following TCR ligation. A role for SLP-76 in additional receptor-mediated
      signaling events is less clear. To define the pattern of SLP-76 expression during
      murine hemopoiesis, we stained cells isolated from various tissues with a
      combination of surface markers followed by intracellular staining with a
      fluorochrome-labeled SLP-76-specific Ab. In the bone marrow, SLP-76 expression is
      largely restricted to cells of granulocyte and monocyte lineage. Heterogeneous
      SLP-76 expression is first detected in the CD44+ CD25- subset within the CD3- CD4
      CD8- thymocyte population. Interestingly, SLP-76 expression increases as
      thymocyte maturation progresses within the CD4- CD8- compartment but decreases as
      cells mature to a CD4+ CD8+ phenotype. SLP-76 expression is then up-regulated
      following selection and concomitant with maturation to a CD4+ or CD8+ phenotype.
      In the periphery, SLP-76 is expressed in T lymphocytes with no detectable
      expression in the B cell compartment. Exposure to the superantigen staphylococcal
      enterotoxin B augments SLP-76 expression in the reactive T cell subset.
      Furthermore, in vitro stimulation with TCR-specific Abs augments the existing
      levels of SLP-76. These data reveal that SLP-76 expression is coordinately
      regulated with surface expression of a pre-TCR or mature TCR complex during
      thymocyte development and that TCR ligation elicits signals that result in
      increased expression of SLP-76.

PMID- 9780154
TI  - Effects of bacterial DNA on cytokine production by (NZB/NZW)F1 mice.
AB  - Microbial DNA has multiple immune effects including the capacity to induce
      polyclonal B cell activation and cytokine production in normal mice. We recently
      described the accelerated induction of anti-DNA Abs in NZB/NZW mice immunized
      with Escherichia coli (EC) dsDNA; paradoxically these mice developed less renal
      disease than unimmunized mice or mice immunized with calf thymus DNA. We
      postulated that alterations in cytokine production induced by bacterial DNA may
      play a key role in renal protection. To determine the effect of bacterial DNA on
      cytokine production in NZB/NZW mice, we measured the serum cytokine levels, cell
      culture supernatant cytokine levels, and number of cytokine-producing splenocytes
      in NZB/NZW mice injected with EC DNA, calf thymus DNA, or an immune active
      oligonucleotide. There was a 10- to 25-fold increase in the number of cells
      secreting IFN-gamma compared with IL-4 in mice immunized with EC DNA. IL-12
      secreting cells were also increased by bacterial DNA immunization. In parallel
      with the increase in IFN-gamma secreting cells, there was a significant rise in
      serum IFN-gamma levels in mice receiving EC DNA. These results indicate that EC
      DNA modulates systemic cytokine levels in NZB/NZW mice, selectively increasing IL
      12 and IFN-gamma while decreasing IL-4 production. The cytokine response of
      NZB/NZW mice to bacterial DNA may be of significance in disease pathogenesis and
      relevant to the treatment of lupus-like disease.

PMID- 9780155
TI  - Development of peptide-selected CD8 T cells in fetal thymic organ culture occurs
      via the conventional pathway.
AB  - Fetal thymic organ culture of TCR transgenic (Tg) tissue has been used to study
      issues of timing and specificity in T cell development. Because most TCR Tgs
      express a rearranged alphabeta TCR on the cell surface at an earlier stage in
      development than normal mice, there is a possibility that the conclusions of
      studies using TCR Tg cultures may not apply to normal development. In particular,
      in our studies of peptide-induced development of CD8 T cells, it is possible that
      the peptide acts on the immature double-negative cell, driving development of CD8
      T cells without passing through a double-positive stage. This issue was examined
      by asking whether MHC class I restriction was required and by analyzing CD8beta
      levels and endogenous TCR alpha chain rearrangements. We found that if
      nonstimulatory peptides were used in fetal thymic organ culture, CD8 T cells
      developed via the conventional pathway, transiting through a double-positive
      stage. However, we could not rule out that cells selected in the presence of
      stimulatory peptides (agonists) did not develop directly from double-negative
      precursors.

PMID- 9780156
TI  - Adhesive and/or signaling functions of CD44 isoforms in human dendritic cells.
AB  - The regulation and function of the CD44 family of surface glycoproteins were
      investigated in human monocyte-derived dendritic cells (DCs). Variant CD44
      isoform transcripts encoding exons v3, v6, and v9 are differently regulated
      during the differentiation of monocytes into DCs. TNF-alpha treatment, which
      induces the maturation of DCs, up-regulates the expression of all v3-, v6-, and
      v9-containing isoforms examined. CD44 molecules are involved in the adhesion of
      DCs to immobilized hyaluronate (HA), and v3- and v6-containing variants
      participate in this function, whereas anti-CD44v9 mAbs were unable to inhibit DC
      adhesion to HA. The consequences of ligand binding to CD44 were examined by
      culturing DCs on dishes coated with HA or various anti-CD44 mAbs. HA, the anti
      pan CD44 mAb J173, and mAbs directed against v6- and v9-containing (but not v3
      containing) isoforms provoked DC aggregation, phenotypic and functional
      maturation, and the secretion of IL-8, TNF-alpha, IL-1beta, and granulocyte
      macrophage CSF. In addition, IL-6, IL-10, and IL-12 were released by DCs
      stimulated with either J173 or HA, although these cytokines were not detected or
      were found only at low levels in the culture supernatants of DCs treated with
      anti-CD44v6 or anti-CD44v9 mAbs. Our study points to distinct capacities of the
      v3-, v6-, and v9-containing isoforms expressed by human DCs to mediate cell
      adhesion to HA and/or a signal inducing DC maturation and the secretion of
      cytokines.

PMID- 9780157
TI  - B lymphocytes are critical antigen-presenting cells for the initiation of T cell
      mediated autoimmune diabetes in nonobese diabetic mice.
AB  - Nonobese diabetic (NOD) mice genetically deficient in B lymphocytes (NODJg
      mu(null)) are resistant to T cell-mediated autoimmune insulin-dependent diabetes
      mellitus (IDDM). Ig infusions from diabetic NOD donors did not abrogate IDDM
      resistance in NODJg mu(null) mice. However, T cell responses to the candidate
      pancreatic beta cell autoantigen glutamic acid decarboxylase (GAD), but not the
      control Ag keyhole limpet hemocyanin, were eliminated in NODJg mu(null) mice. To
      initially test whether they contribute to IDDM as APC, NOD B lymphocytes were
      transferred into NODJg mu(null) recipients. B lymphocytes transferred into
      unmanipulated NODJg mu(null) recipients were rejected by MHC class I-restricted T
      cells. Stable T and B lymphocyte repopulation was achieved in irradiated NODJg
      mu(null) mice reconstituted with syngeneic bone marrow admixed with NOD B
      lymphocytes. IDDM susceptibility was restored in NODJg mu(null) mice
      reconstituted with syngeneic marrow plus B lymphocytes, but not with syngeneic
      marrow only. T cell responses to GAD were restored only in NODJg mu(null) mice
      reconstituted with syngeneic marrow plus B lymphocytes. Hence, B lymphocytes
      appear to contribute to IDDM in NOD mice as APC with a preferential ability to
      present certain beta cell Ags such as GAD to autoreactive T cells.

PMID- 9780158
TI  - Positive and negative regulation of human T cell activation mediated by the CTLA
      4/CD28 ligand CD80.
AB  - CD28 and CTLA-4 are related receptors that differentially regulate T cell
      activation. Despite the fact that they bind the same ligands, CD28 is a classical
      costimulator enhancing proliferation whereas CTLA-4 appears to perform negative
      regulatory functions. In this study, we have utilized the natural ligand for CD28
      and CTLA-4 (CD80) to determine under what circumstances positive and negative
      effects are operative. We show here that the stimulation of purified human T
      cells with phorbol ester and ionomycin is inhibited in the presence of Chinese
      hamster ovary (CHO) cells expressing CD80. This inhibition is reversed by
      blocking with both anti-CD80 or Fab fragments of anti-CTLA-4 but also requires
      CD28 engagement. Furthermore, we show that the inhibitory function of CD80
      requires elevated intracellular calcium since inhibition was observed only in the
      presence of ionomycin. In the absence of intracellular calcium elevation, CTLA-4
      was not expressed at the cell surface, and CD80 acted positively as a
      costimulator of T cells, via CD28. These results demonstrate that the natural
      ligand CD80 can either costimulate or inhibit T cell responses depending on the
      conditions of T cell stimulation.

PMID- 9780159
TI  - Functional analysis of peripheral blood B cells in patients with X-linked
      agammaglobulinemia.
AB  - X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disease caused by
      mutations of Bruton tyrosine kinase (Btk); Btk plays an essential role in the
      development of mature B cells. However, small numbers of B cells ("leaky B
      cells") are present in the peripheral blood of most XLA patients. In this study,
      we analyzed the function of these leaky B cells obtained from XLA patients.
      Enough numbers of B cells were available for analysis from five of nine XLA
      patients originally screened. Sequence analysis revealed missense mutations of
      Btk in four of the five XLA patients. No mutation was found in the coding region
      of Btk in one patient. Western blotting and/or flow cytometric analysis failed to
      detect Btk protein in all five patients. B cells isolated from peripheral blood
      of these XLA patients were CD5-, CD20+, CD19+, and CD21-. If stimulated with anti
      CD40 and IL-4, XLA B cells proliferated normally and produced significant amounts
      of IgE. Anti-CD40 stimulation of XLA B cells resulted in normal expression of
      CD23. In addition, three of the five XLA patients studied were immunized with
      bacteriophage phiX174 and produced low but detectable levels of antiphage
      specific Ab. Similarly, X-linked immunodeficiency mice, which carry a missense
      mutation in Btk, produced substantial amounts of antiphage Ab. These results
      indicate that CD40 signaling is intact in B cells lacking demonstrable Btk, and
      that leaky B cells in XLA patients can proliferate, undergo isotype switching,
      and differentiate into specific Ab-producing cells.

PMID- 9780160
TI  - Cyclosporin A enhances IL-12 production by CpG motifs in bacterial DNA and
      synthetic oligodeoxynucleotides.
AB  - Certain sequences of nucleotides (CpG motifs) in bacterial DNA or synthetic
      oligonucleotides (CpG DNA) promote the production of proinflammatory cytokines,
      including TNF-alpha, IFN-gamma, IL-6, and IL-12. Here we demonstrate that the
      immunosuppressant cyclosporin A (CsA) unexpectedly enhanced CpG DNA-induced IL-12
      production in murine splenocytes. CsA did not inhibit CpG DNA-induced TNF-alpha
      or IL-6 production, but decreased the production of IFN-gamma by CpG DNA. Upon
      examining mechanisms by which CsA increases IL-12 production, we found that CpG
      DNA can also induce IL-10 production in B cells and that this production was
      sensitive to CsA. IL-10 has anti-inflammatory effects and can reduce the
      production of IL-12. To determine the possible role of CsA-modulated IL-10
      production in mediating the increased IL-12 levels, splenocytes from IL-10 gene
      disrupted mice (IL-10 -/-) and splenocytes cultured in anti-IL-10 Ab were
      studied. CpG DNA-stimulated IL-10 (-/-) splenocytes demonstrated no increase in
      IL-12 levels in the presence of CsA. Anti-IL-10 Ab treatment of normal
      splenocytes increased the magnitude of CpG DNA-induced IL-12 production to that
      seen with CsA. These results suggest that CpG DNA induces CsA-sensitive IL-10
      production in B cells and that IL-10 acts as a negative feedback regulator of CpG
      DNA-induced IL-12 production.

PMID- 9780161
TI  - FLIP prevents apoptosis induced by death receptors but not by perforin/granzyme
      B, chemotherapeutic drugs, and gamma irradiation.
AB  - FLICE-inhibitory protein, FLIP (Casper/I-FLICE/FLAME-1/CASH/CLARP/MRIT), which
      contains two death effector domains and an inactive caspase domain, binds to FADD
      and caspase-8, and thereby inhibits death receptor-mediated apoptosis. Here, we
      characterize the inhibitory effect of FLIP on a variety of apoptotic pathways.
      Human Jurkat T cells undergoing Fas ligand-mediated apoptosis in response to CD3
      activation were completely resistant when transfected with FLIP. In contrast, the
      presence of FLIP did not affect apoptosis induced by granzyme B in combination
      with adenovirus or perforin. Moreover, the Fas ligand, but not the
      perforin/granzyme B-dependent lytic pathway of CTL, was inhibited by FLIP.
      Apoptosis mediated by chemotherapeutic drugs (i.e., doxorubicin, etoposide, and
      vincristine) and gamma irradiation was not affected by FLIP or the absence of
      Fas, indicating that these treatments can induce cell death in a Fas-independent
      and FLIP-insensitive manner.

PMID- 9780162
TI  - The regulation of CD95 ligand expression and function in CTL.
AB  - Previous studies with CTL lines and CTL hybridomas have suggested that functional
      CD95 (APO-1/Fas)-ligand (CD95L) expression on effector CTLs is a consequence of
      specific CTL-target recognition and TCR triggering of newly transcribed CD95L.
      Such a control on the expression of CD95L could provide a double safeguard for
      killing only cognate target cells. Here the regulation of CD95L expression and
      function was tested in in vivo primed, alloreactive peritoneal exudate CTL (PEL)
      from perforin-deficient (P0) mice. CD95L-based, PEL-mediated cytotoxicity was
      blocked by brefeldin A, an inhibitor of intracellular protein transport, but not
      by the protein synthesis inhibitor emetine, the immunosuppressive drug
      cyclosporin A, or the DNA transcription inhibitor actinomycin D. CD95L mRNA
      transcripts in freshly isolated PEL were shown by RT-PCR; CD95L surface
      expression was evident by staining with Fas-Fc as well as CD95L Abs. Undiminished
      CD95L expression and cytocidal activity were found in PEL incubated for 48 h in
      culture, without adding Ag, mitogen, or cytokines. PEL expressed functional
      CD95L, yet exhibited target cell-specific killing, except when encountering high
      CD95-expressing cells. The results indicate that PEL use CD95L probably expressed
      in the Golgi and/or on the cell surface and do not require newly transcribed
      CD95L upon target cell conjugation. Hence the TCR-triggered recruitment of
      preformed CD95L, rather than its biosynthesis, controls CD95L-based specific
      lysis induced by CTL.

PMID- 9780163
TI  - TGF-beta1 somatic gene therapy prevents autoimmune disease in nonobese diabetic
      mice.
AB  - Nonobese diabetic (NOD) mice develop insulitis and diabetes through an autoimmune
      process. Since TGF-beta1 down-regulates many immune responses, we hypothesized
      that TGF-beta1 could prevent disease in NOD mice and that there would be several
      advantages to cytokine delivery by a somatic gene therapy approach. We opted for
      i.m. injection of a naked plasmid DNA expression vector encoding murine TGF-beta1
      (pCMV-TGF-beta1). Treatment with pCMV-TGF-beta1 resulted in the retention and
      expression of the vector in muscle cells, associated with a considerable
      elevation in the plasma levels of TGF-beta1, that was not observed in control
      vector-treated mice. The levels of TGF-beta1 produced were sufficient to exert
      immunosuppressive effects. Delayed-type hypersensitivity responses were
      suppressed, and autoimmunity-prone NOD mice were protected from insulitis and
      diabetes in models of cyclophosphamide-accelerated and natural course disease. In
      pCMV-TGF-beta1-treated mice, pancreatic IL-12 and IFN-gamma mRNA expression was
      depressed, and the ratio of IFN-gamma to IL-4 mRNA was decreased, as determined
      by semiquantitative reverse-transcription PCR. In contrast, NOD mice injected
      with a vector encoding the proinflammatory cytokine IFN-gamma developed diabetes
      earlier. Intramuscular administration of cytokine-encoding plasmid vectors proved
      to be an effective method of cytokine delivery in these mice, and altered
      autoimmune disease expression.

PMID- 9780164
TI  - Molecular mechanisms of immune-mediated lysis of murine renal cancer:
      differential contributions of perforin-dependent versus Fas-mediated pathways in
      lysis by NK and T cells.
AB  - Mice bearing the experimental murine renal cancer Renca can be successfully
      treated with some forms of immunotherapy. In the present study, we have
      investigated the molecular pathways used by NK and T cells to lyse Renca cells.
      Renca cells normally express low levels of Fas that can be substantially enhanced
      by either IFN-gamma or TNF-alpha, and the combination of IFN-gamma + TNF-alpha
      synergistically enhances cell-surface Fas expression. In addition, cells
      pretreated with IFN-gamma and TNF-alpha are sensitive to lysis mediated by Fas
      ligand (FasL)-expressing hybridomas (dllS), cross-linking of anti-Fas Abs or
      soluble Fas (FasL). Lysis via Fas occurs by apoptosis, since Renca shows all the
      typical characteristics of apoptosis. No changes in levels of bcl-2 were observed
      after cytokine treatments. We also examined cell-mediated cytotoxic effects using
      activated NK cells and T cells from gld FasL-deficient mice, and perforin
      deficient mice, as well as wild-type C57BL/6 and BALB/c mice. Interestingly, the
      granule-mediated pathway predominated in killing of Renca by activated NK cells,
      while the Fas/FasL pathway contributed significantly to cell-mediated killing of
      Renca by activated T cells. These results suggest that killing of Renca tumor
      cells by immune effector cells can occur by both granule and Fas-mediated
      cytotoxicity. However, for the Fas-mediated pathway to function, cell surface
      levels of Fas need to be increased beyond a critical threshold level by
      proinflammatory cytokines such as IFN-gamma and TNF-alpha.

PMID- 9780165
TI  - Initiation of the autologous mixed lymphocyte reaction requires the expression of
      costimulatory molecules B7-1 and B7-2 on human peripheral blood dendritic cells.
AB  - The human autologous mixed lymphocyte reaction (AMLR) consists of a proliferative
      response of primarily CD4+ T lymphocytes stimulated by autologous non-T cells
      expressing class II MHC-encoded gene products and is thought to represent a self
      recognitive mechanism that might be important in regulating the cellular
      interactions involved in the generation of normal immune responses. To further
      define appropriate stimulator cell populations, as well as the molecular
      mechanism responsible for the initiation of AMLR, we compared the T cell
      stimulatory capacity of highly purified populations of peripheral blood dendritic
      cells (DCs) and monocytes (Mos) under serum-free conditions, thus carefully
      avoiding the presence of xenogeneic Ags. Whereas both freshly isolated Mos and
      DCs were found to be poor stimulators of autologous T cell proliferation,
      preactivation of DCs, but not of Mos, for 48 h with granulocyte-macrophage CSF
      led to a 113-fold increase in DC stimulatory capacity. AMLR was inhibited by mAbs
      against HLA-DR and CD4 molecules, and, in addition, showed a higher dependence on
      the granulocyte-macrophage CSF-induced up-regulation and/or de novo expression of
      the costimulatory molecules B7-2 and, in particular, B7-1 as compared with an Ag
      specific or allogeneic MLR. Thus, our data suggest that the high density of
      costimulatory molecules together with MHC class II molecules on competent APCs
      appear to be the major triggers for the initiation of AMLR.

PMID- 9780166
TI  - Deletion of bone marrow stromal cell antigen-1 (CD157) gene impaired systemic
      thymus independent-2 antigen-induced IgG3 and mucosal TD antigen-elicited IgA
      responses.
AB  - Bone marrow stromal cell Ag-1 (BST-1; CD157)-deficient mice were generated to
      examine the immunologic roles of the molecule in vivo. In BST-1(-/-) mice, the
      development of peritoneal B-1 cells was delayed, and CD38(low/-) B-lineage cells
      were increased in the bone marrow and spleen. Partial impairment of thymus
      independent (TI-2) and thymus-dependent (TD) Ag-specific immune responses was
      noted in the systemic and mucosal compartments of BST-1(-/-) mice, respectively.
      Although serum Ig levels as well as TD and TI-1 Ag-specific systemic immune
      responses were normal, the TI-2 Ag-induced IgG3 response was selectively
      impaired. Oral immunization of BST-1(-/-) mice with cholera toxin, a potent TD Ag
      for the induction of IgA response, resulted in the poor production of Ag-specific
      Abs at the intestinal mucosa accompanied by the reduced number of Ag-specific IgA
      producing cells in the lamina propria. These results indicate that BST-1 has
      roles in B cell development and Ab production in vivo.

PMID- 9780167
TI  - Critical involvement of Tcf-1 in expansion of thymocytes.
AB  - T cell maturation in Tcf-1(-/-) mice deteriorates progressively and halts
      completely around 6 mo of age. During fetal development thymocyte subpopulations
      seem normal, although total cell numbers are lower. By 4 to 6 wk of age, obvious
      blockades in the differentiation of CD4- 8- thymocytes are observed at two
      distinct stages (CD44+ 25+ and CD44- 25-), both of which are normally
      characterized by extensive proliferation. This lack of thymocyte expansion and/or
      differentiation was also observed when Tcf-1(-/-) progenitor cells from the aorta
      gonad-mesonephros region (embryonic day 11.5), fetal liver (embryonic day
      12.5/14.5), and fetal bone marrow (embryonic day 18.5) were allowed to
      differentiate in normal thymic lobes (fetal thymic organ cultures) or were
      injected intrathymically into normal recipients. Despite these apparent defects
      in thymocyte differentiation and expansion, adult Tcf-1(-/-) mice are
      immunocompetent, as they generate virus neutralizing Abs at normal titers.
      Furthermore, their peripheral T cells have an activated phenotype (increased CD44
      and decreased CD62L expression) and proliferate normally in response to Ag or
      mitogen, suggesting that these cells may have arisen from the early wave of
      development during embryogenesis and are either long lived or have subsequently
      been maintained by peripheral expansion. As Tcf-1 is a critical component in the
      Wnt/beta-catenin signaling pathway, these data suggest that Wnt-like factors play
      a role in the expansion of double-negative thymocytes.

PMID- 9780168
TI  - Normal thymic selection of TCR transgenic CD4 T cells, but impaired survival in
      the periphery despite the presence of selecting MHC molecules.
AB  - In this paper, we investigate selection in the thymus and survival in the
      periphery of CD4 T cells, which carry a major histocompatibility class II
      restricted transgenic TCR (A18 TCRtg) specific for a natural self Ag, the fifth
      component of complement (C5). A18 TCRtg thymocytes develop normal numbers of CD4
      single-positive (SP) thymocytes, but do not show pronounced overselection as do
      some other TCR transgenic strains. CD4 SP cells are mature as judged by
      termination of CD8 synthesis, resistance to cortisone, and functional competence.
      The kinetics of positive selection, determined by BrdU labeling, are very fast.
      CD4 SP thymocytes are demonstrable within 2 days of labeling, and within 8 days
      after labeling a large proportion (20%) of lymph node T cells are recent thymic
      emigrants. The high number of recent thymic emigrants suggests rapid turnover of
      CD4 T cells in the periphery, which was confirmed by thymectomy and determination
      of CD4 T cell life spans. A18 TCRtg T cells have a t(1/2) of approximately 6 wk,
      despite the presence of selecting MHC molecules. This explains the failure to
      accumulate high numbers of peripheral T cells and suggests that the MHC-bound
      ligand(s) responsible for initiating survival signals is limiting for the
      selection and maintenance of A18 transgenic CD4 T cells.

PMID- 9780170
TI  - Localization of splenic B cells activated for switch recombination by in situ
      hybridization with Igamma1 switch transcript and Rad51 probes.
AB  - B cells are activated for switch recombination by signals from Th cells, but the
      site at which this first occurs in vivo has yet to be identified. By in situ
      hybridization of splenic sections using riboprobes specific for the Igamma1
      switch transcript and Rad51 mRNA, we have visualized B cells that are newly
      activated for switch recombination and characterized the spatial and temporal
      patterns of Igamma1 and Rad51 mRNA expression. Within 2 days after immunization
      with (4-hydroxy-3-nitrophenyl)acetyl-chicken gamma-globulin, expression of
      Igamma1 switch transcripts and Rad51 mRNA was evident and was localized to B220+
      B cells clustered within the T cell-rich periarteriolar lymphoid sheath (PALS)
      and surrounding follicles. By Ab staining, we have shown previously that cells
      switching from IgM to IgG expression can be visualized at 3 to 5 days
      postimmunization and colocalize to clusters of Rad51+ cells. Hybridization of
      adjacent sections with probes for Cmu and Cgamma1 mRNA now shows that switching
      from mu to gamma expression occurs within Rad51+ Igamma1+ regions of the PALS and
      peaks between days 3 and 5. Colocalized expression of Igamma1 and Rad51
      transcripts was observed from days 2 through 12 of the immune response. Igamma1
      and Rad51 transcripts were down-regulated but still detectable at 12 days
      postimmunization, when they were evident in peanut agglutinin-positive germinal
      center B cells. Taken together, these observations show that B cells are first
      activated for switch recombination in the T cell-rich PALS.

PMID- 9780169
TI  - Lipid vesicle size determines the Th1 or Th2 response to entrapped antigen.
AB  - Understanding the factors that control the differential induction of Th1 and Th2
      responses is a key immunologic objective with profound implications for
      vaccination and immunotherapy of infectious and autoimmune diseases. Using Ag
      formulated in lipid vesicles prepared from nonionic surfactants, we describe a
      novel mechanism influencing the balance of the Th1 or Th2 response. Our results
      indicate that inoculation of BALB/c mice with vesicles with a mean diameter > or
      = 225 nm preferentially induces Th1 responses, as characterized by increased
      titers of IgG2a in plasma and elevated IFN-gamma production by lymph node cells.
      However, preparation of the same quantity of Ag in vesicles with mean diameter of
      < or = 155 nm induces a Th2 response, as identified by IgG1 in the absence of
      IgG2a production and increased lymph node IL-5 production. Although large (> or =
      225 nm) vesicles could induce IL-12 production, smaller vesicles (< or = 155 nm)
      could not. However, small vesicles did induce higher levels of IL-1beta
      production by macrophages than larger vesicles. The role of IL-12 in this
      response was confirmed in IL-12-deficient mice, whose spleen cells failed to
      produce IFN-gamma following in vivo priming with Ag prepared in large vesicles.
      Our results therefore indicate that macrophages respond to endocytosis of large
      or small vesicles by producing different patterns of cytokines that can
      subsequently direct the immune response toward a Th1 or a Th2 phenotype.

PMID- 9780171
TI  - Affinity and kinetic analysis of the molecular interaction of ICAM-1 and
      leukocyte function-associated antigen-1.
AB  - LFA-1 is a member of the beta2 integrin family, and interacts with ICAM-1, a
      member of the Ig superfamily containing five Ig-like domains. Interaction of LFA
      1 with ICAM-1 is important in a number of cellular events, including Ag-specific
      T cell activation and leukocyte transendothelial migration, which are known to be
      typically transient and highly regulated. In this study, we have used surface
      plasmon resonance technology to study the ICAM-1/LFA-1 interaction at the
      molecular level. A soluble form of LFA-1 (sLFA-1), normally expressed as two
      noncovalently associated membrane-bound subunits, has been produced, and its
      interaction with ICAM-1 has been examined. The kinetic analysis of a monomeric
      sLFA-1 binding to the first two domains of ICAM-1 expressed as a chimeric IgG
      fusion protein (D1D2-IgG) revealed that sLFA-1 was bound to the D1D2-IgG chimera
      with a Kd of 500 nM and dissociated with a k(diss) of 0.1 s(-1). Monomeric
      membrane-bound LFA-1 purified from plasma membranes showed a similar kinetic to
      sLFA-1. These results suggest that the monovalent interaction between ICAM-1 and
      LFA-1 has a primarily high affinity and a slow dissociation rate constant as
      compared with other adhesion molecules, suggesting a potential mechanism for firm
      adhesion.

PMID- 9780172
TI  - Rapid extracellular degradation of synthetic class I peptides by human dendritic
      cells.
AB  - Dendritic cells (DCs) effectively process exogenous and endogenous Ag and present
      peptide in the context of both class I and class II molecules. We have
      demonstrated that peripheral blood DCs efficiently degrade synthetic class I
      peptides at their cell surface within minutes as determined by analyzing DC
      supernatants by HPLC. Fragments were verified as bona fide cleavage products by
      direct sequencing using collision-induced dissociation tandem mass spectrometry.
      The predominant degradative activities were 1) not secreted but associated with
      activity at the plasma membrane, 2) ecto-orientated, 3) not induced by peptide
      specific interactions, and 4) not associated with nonspecific uptake. Sequence
      analysis indicated that both N- and C-terminal as well as endoproteolytic events
      were occurring at the cell surface. The primary exoproteolytic event was
      identified as CD13 or CD13-like activity through inhibition studies and could be
      inhibited by ubiquitin and metal-chelating agents. Endoproteolytic events could
      be inhibited in the presence of DTT, but the precise nature of this enzyme is
      still undetermined. Compared with the starting monocyte population, DCs cultured
      in the presence of granulocyte-macrophage CSF/IL-4 exhibited the highest
      degradative rate (4.3 nmol/min), followed by cultured monocytes (2.9 nmol/min)
      and freshly isolated monocytes (1.0 nmol/min). In addition to increased enzymatic
      activity, a change in substrate specificity was noted. Results are discussed with
      respect to APC loading, and alternatives are offered for circumventing such
      degradation.

PMID- 9780173
TI  - Murine Langerhans cells cultured under serum-free conditions mature into potent
      stimulators of primary immune responses in vitro and in vivo.
AB  - The ability of Ag-pulsed dendritic cells (DC) to induce primary immune responses
      has led them to be used for vaccination purposes. However, irrelevant Ags (e.g.,
      FCS) can also be taken up by DC during their isolation and culture and then
      presented in vivo. To circumvent this, we have established a serum-free (SF)
      culture system. Murine epidermal cell (EC) suspensions were prepared with and
      without FCS and cultured for 3 days either in SF or FCS-containing medium. In
      spite of the lower Langerhans cell (LC) yields under SF conditions, both SF- and
      FCS-cultured LC (SF-cLC, FCS-cLC) underwent a similar maturation process, as
      evidenced by a similar increase in the cell surface expression of MHC class II
      and of costimulatory molecules. The further observation that SF-EC cultures
      elaborated comparable amounts of granulocyte-macrophage (GM)-CSF as FCS-cultured
      EC, but were relatively impaired in their IL-1alpha and TNF-alpha production,
      supports the role of GM-CSF in LC maturation and, less so, in LC survival.
      Functionally, freshly isolated SF-LC compared with FCS-LC in their Ag-processing
      capacity. Three-day-cultured SF-LC were as potent stimulators of polyclonal T
      cell responses and of the primary allogeneic MLR as FCS-cLC, but were relatively
      poor activators of naive, syngeneic CD4+ T cells. In vivo, hapten-modified SF-cLC
      induced a contact hypersensitivity response similar in magnitude and kinetics to
      that evoked by FCS-cLC. Our data show that, in the absence of serum and exogenous
      cytokines, LC mature into potent activators of T cell responses and could thus be
      a valuable cellular source for DC-based immunotherapy.

PMID- 9780174
TI  - Inhibitory and stimulatory functions of paired Ig-like receptor (PIR) family in
      RBL-2H3 cells.
AB  - In this study, we demonstrate potent regulatory function of the murine killer
      cell inhibitory receptor-like molecules, paired Ig-like receptors (PIRs) or p91,
      using chimeric receptors expressed on the rat basophilic leukemia cell line RBL
      2H3. One of the chimeras, which has the transmembrane and cytoplasmic domain of
      PIR-B fused to the extracellular portion of type IIB receptor for IgG, was able
      to inhibit the type I receptor for IgE-mediated degranulation response upon
      coaggregation. This chimera also suppressed cytoplasmic Ca2+ mobilization in the
      presence and absence of calcium ion in the extracellular medium. Tyrosine to
      phenylalanine point mutations at the third and fourth immunoreceptor tyrosine
      based inhibitory motif-like sequences of PIR-B attenuated the inhibitory effects
      on degranulation and on cytoplasmic Ca2+ mobilization, indicating the important
      role of these tyrosines for the delivery of negative signal. In contrast, the
      cross-linking of another chimeric receptor composed of the type IIB receptor for
      IgG extracellular portion and the transmembrane and short cytoplasmic sequence of
      PIR-A elicited Ca2+ mobilization and degranulation. These results indicate that
      PIR molecules may regulate cellular functions both positively and negatively.

PMID- 9780175
TI  - Large protein fragments as substrates for endocytic antigen capture by MHC class
      II molecules.
AB  - Although the binding sites of MHC class II molecules can accommodate longer
      ligands, peptides of 15 to 20 residues are the primary form of processed Ag
      recovered from class II dimers isolated from living cells. These peptides are
      derived from intact Ags by proteolysis in endocytic organelles, where binding to
      class II dimers also occurs. Whether generation of these short peptides typically
      precedes association with class II molecules, or whether class II molecules
      initially bind to unfolded proteins or large protein fragments, followed by
      degradation of the unprotected regions, remains unknown. Here we report the
      identification of an SDS-stable, long-lived, 120-kDa complex composed of two
      class II dimers bound to a common large Ag fragment. This complex is produced
      within the endocytic pathway from newly synthesized MHC class II molecules
      following exposure of the cells to exogenous hen egg lysozyme. These data suggest
      that a major pathway of Ag processing involves the initial binding of class II
      heterodimers to large protein substrates upon exposure of regions with suitable
      motifs, followed by cleavage and/or trimming of the exposed protein around this
      bound region. This sequence of events during Ag processing may provide a partial
      molecular explanation for the immunodominance of certain determinants in protein
      Ags.

PMID- 9780176
TI  - CD3/TCR complex-associated lymphocyte activation gene-3 molecules inhibit CD3/TCR
      signaling.
AB  - The lymphocyte activation gene-3 (LAG-3) molecule is a T cell activation Ag
      closely related to CD4 at the gene and protein levels. We investigated whether
      LAG-3 itself may down-regulate the immune response by interfering with TCR
      signaling. The binding of Ab to the LAG-3 molecule followed by cross-linking (XL)
      inhibits cell proliferation and cytokine secretion in response to CD3XL on
      activated T cells. LAG-3XL-induced down-regulation is associated with functional
      unresponsiveness, as well as with high CD25 expression levels and reversion by
      exogenous IL-2. It is also associated with a down-modulation of CD3/TCR complex
      expression. At the biochemical level, LAG-3XL inhibits calcium response to CD3
      stimulation. This inhibition is observed with different LAG-3- and CD3-specific
      mAbs on condition that the two receptors are cross-linked together. Finally, the
      capping of CD3 was shown to induce cocapping of LAG-3 molecules. Together, these
      results show that CD3/TCR complex-associated LAG-3 molecules can play an active
      role in negatively regulating the CD3/TCR activation pathway. They ultimately
      suggest that LAG-3 is an inhibitory receptor in activated T lymphocytes.

PMID- 9780177
TI  - Genomics, isoforms, expression, and phylogeny of the MHC class I-related MR1
      gene.
AB  - A growing number of non-MHC-encoded class I-related molecules have been shown to
      perform diverse, yet essential, functions. These include T cell presentation of
      bacterially derived glycolipidic Ags by CD1, transcytosis of maternal IgG by the
      neonatal Fc receptor, enriched presence and plausible function within exocrine
      fluids of the Zn-alpha2-glycoprotein, subversion of NK cytolytic activity by the
      CMV UL18 gene product, and, finally, crucial involvement in iron homeostasis of
      the HFE gene. A recently described member of this family is the MHC class-I
      related (MR1) gene. The most notable feature of MR1 is undoubtedly its relatively
      high degree of sequence similarity to the MHC-encoded classical class I genes.
      The human chromosome 1q25.3 MR1 locus gives rise not only to the originally
      reported 1,263-bp cDNA clone encoding a putative 341-amino acid polypeptide
      chain, but to many additional transcripts in various tissues as well. Here we
      define the molecular identity of all human and murine MR1 isoforms generated
      through a complex scenario of alternative splicing, some encoding secretory
      variants lacking the Ig-like alpha3 domain. Moreover, we show ubiquitous
      transcription of these MR1 variants in several major cell lineages. We
      additionally report the complete 18,769-bp genomic structure of the MR1 locus,
      localize the murine orthologue to a syntenic segment of chromosome 1, and provide
      evidence for conservation of a single-copy MR1 gene throughout mammalian
      evolution. The 90% sequence identity between the human and mouse MR1 putative
      ligand binding domains together with the ubiquitous expression of this gene favor
      broad immunobiologic relevance.

PMID- 9780178
TI  - Definition of natural T cell antigens with mimicry epitopes obtained from
      dedicated synthetic peptide libraries.
AB  - Progress has recently been made in the use of synthetic peptide libraries for the
      identification of T cell-stimulating ligands. T cell epitopes identified from
      synthetic libraries are mimics of natural epitopes. Here we show how the mimicry
      epitopes obtained from synthetic peptide libraries enable unambiguous
      identification of natural T cell Ags. Synthetic peptide libraries were screened
      with Mycobacterium tuberculosis-reactive and -autoreactive T cell clones. In two
      cases, database homology searches with mimicry epitopes isolated from a dedicated
      synthetic peptide library allowed immediate identification of the natural
      antigenic protein. In two other cases, an amino acid pattern that reflected the
      epitope requirements of the T cell was determined by substitution and omission
      mixture analysis. Subsequently, the natural Ag was identified from databases
      using this refined pattern. This approach opens new perspectives for rapid and
      reliable Ag definition, representing a feasible alternative to the biochemical
      and genetic approaches described thus far.

PMID- 9780179
TI  - Comparisons of the ability of human IgG3 hinge mutants, IgM, IgE, and IgA2, to
      form small immune complexes: a role for flexibility and geometry.
AB  - Various native and hinge-modified forms of Ig with identical Ids were reacted
      with an anti-Id mAb, and the resultant immune complexes were analyzed by negative
      stain immunoelectron microscopy. Complexes were scored for their geometry (linear
      versus ring complexes) and size (dimer, trimer, etc.). Ring dimers are the
      thermodynamically most favorable configuration, unless inhibited by steric and/or
      flexibility constraints. We found ring dimerization to correlate with the length
      of the upper, but not middle or lower, hinge. In contrast, the geometry and size
      of complexes of those molecules lacking formal hinges were unpredictable. A
      hingeless IgG mutant and native IgE readily formed ring dimers. Remarkably,
      monomeric IgM formed more ring dimers than any of the other Igs tested, including
      IgG3. We also tagged the Fab arms and measured the mean Fab-Fab angles and the
      degree of angular variation for each type of Ig. Surprisingly, IgM proved the
      most flexible by this assay. In hinged Igs, there was a correlation between
      length of the upper hinge and Fab-Fab flexibility. In contrast, we found no
      correlation between the mean Fab-Fab angle in uncomplexed Igs and their ability
      to dimerize with anti-Id mAb. These data suggest that the physicochemical methods
      typically used to evaluate molecular flexibility are often of low predictive
      value when tested in a functional assay.

PMID- 9780180
TI  - Production of IgM hexamers by normal and autoimmune B cells: implications for the
      physiologic role of hexameric IgM.
AB  - Secreted IgM is predominantly found as pentameric molecules, but IgM can also be
      secreted as hexamers by B cell lines. Murine hexamers activate the complement
      cascade more efficiently than pentamers, but the physiologic significance of
      hexameric IgM remains unknown. Here, we report that IgM hexamers and pentamers
      are cleared from the circulation with similar kinetics, suggesting that the
      predominance of pentameric IgM in vivo reflects the regulation of polymer
      assembly and secretion in responding B cells. Normal IgM-secreting B cells,
      particularly those from the peritoneal cavity, are capable of secreting abundant
      hexameric IgM in vitro. The disparity between the ability of B cells to secrete
      IgM hexamers in vitro and the paucity of this polymer in vivo suggest that IgM
      hexamers might be deleterious. In support of this, we demonstrate that the
      autoantibodies from a number of patients with cold agglutinin (CA) disease
      include both IgM hexamers and pentamers. The CA IgM hexamers lyse human
      erythrocytes in the presence of human complement more efficiently than CA IgM
      pentamers, suggesting a potential role for hexameric IgM in the pathogenesis of
      this autoimmune syndrome.

PMID- 9780181
TI  - The role of Ets-1 in mast cell granulocyte-macrophage colony-stimulating factor
      expression and activation.
AB  - Ets-1 is a transcription factor with restricted expression in lymphocytes, and it
      has been implicated in the regulation of T cell genes such as TCR alpha, TCR
      beta, CD4, IL-2, and TNF-alpha. We show in this study that Ets-1 is also
      expressed in some mast cells constitutively and can be induced in primary mast
      cells with stimuli that activate mast cells. We also show that Ets-1 plays a role
      in the regulation of granulocyte-macrophage CSF (GM-CSF), a cytokine expressed by
      activated mast cells. We have characterized a murine growth factor-independent
      mast cell line, FMP6-, derived from a factor-dependent cell line, FMP1.6. FMP6-
      has acquired a distinct connective tissue mast cell-like phenotype, as
      characterized by the expression of mast cell proteases MMCP-4 and MMCP-6,
      expression of IL-12, and the down-regulation of IL-4. The parental FMP1.6 cell
      line displays a mucosal mast cell-like phenotype. FMP6- cells have increased Ets
      1 expression and achieve growth-factor independence by the autocrine production
      of GM-CSF and IL-3. Transient transfection of an Ets-1 expression construct in
      FMP6- cells results in transactivation of a GM-CSF reporter, while a point
      mutation in the consensus Ets binding site in the conserved lymphokine element,
      CLE0, abolishes Ets-1 transactivation. Importantly, antisense Ets-1 demonstrates
      an ability to repress the activity of the GM-CSF reporter. These data suggest a
      role for Ets-1 in mast cell growth regulation and activation, and because of the
      central role of mast cells in inflammatory processes, such as asthma and
      rheumatoid arthritis, they identify Ets-1 as potentially contributing to the
      pathophysiology of such diseases.

PMID- 9780182
TI  - Cloning, structure, and function of two rainbow trout Bf molecules.
AB  - The factor B (Bf) and C2 complement genes are closely linked within the MHC class
      III region and are thought to have arisen by gene duplication from a single gene
      encoding an ancestral molecule; the animal phyla in which this duplication event
      took place is unknown. Two teleost fish, (zebrafish and medaka fish) have each
      been shown to possess only a single molecule that shows an equivalent degree of
      similarity to mammalian Bf and C2. In contrast, here we present the
      characterization of two factor B molecules (Bf-1 and Bf-2) in another teleost
      fish (the rainbow trout) that are about 9% more similar to mammalian factor B
      than C2, yet play a role in both alternative and classical pathways of complement
      activation. The full lengths of Bf-1 and Bf-2 cDNAs are 2509 and 2560 bp,
      respectively, and their deduced amino acid sequences are 75% identical. Both
      trout Bf genes are mainly expressed in liver and appear to be single-copy genes.
      The isolated Bf-1 and Bf-2 proteins are able to form the alternative pathway C3
      convertase and are cleaved (in the presence of purified trout C3, trout factor D,
      and Mg2+ EGTA) into Ba- and Bb-like fragments in a manner similar to that seen
      for mammalian factor B. The most remarkable feature of trout Bf-2 is its ability
      to restore the hemolytic activity of trout Bf-depleted serum through both the
      alternative and classical pathways; whether Bf-1 possess similar activity is
      unclear at present.

PMID- 9780183
TI  - A nontoxic adjuvant for mucosal immunity to pneumococcal surface protein A.
AB  - In this study, we demonstrated that pneumococcal surface protein A (PspA) nasally
      administered with a nontoxic A subunit mutant of cholera toxin (mCT) S61F
      elicited a protective immune response. Immunization with PspA and mCT elicited
      higher levels of PspA-specific IgG and IgA Abs in serum and of IgG and IgA anti
      PspA Ab-forming cells in spleens, cervical lymph nodes (CLN), and lung tissue
      when compared to nonimmunized mice. Furthermore, significant PspA-specific IgA
      Abs were induced in saliva and nasal secretions. These responses were dependent
      on the use of mCT as a mucosal adjuvant. The PspA-specific Ab responses induced
      by mCT S61F were comparable with those induced by native CT (nCT). Analysis of
      cytokine responses showed that nasal PspA plus mCT S61F enhanced the induction of
      PspA-specific CD4+ T cells producing IL-4 but not IFN-gamma in CLN at both the
      protein and mRNA levels. Importantly, significant numbers of mice intranasally
      immunized with PspA plus mCT S61F were protected from lethal challenge with
      capsular serotype 3 Streptococcus pneumoniae A66. These results show that
      intranasal administration of PspA together with mCT S61F is an effective mucosal
      vaccine against pneumococcal infection and induces CD4+ Th2-type cells, which
      provide help for both mucosal and systemic Ab responses.

PMID- 9780185
TI  - The schistosome granuloma: characterization of lymphocyte migration, activation,
      and cytokine production.
AB  - Granuloma formation and its regulation are dependent on lymphocytes. Therefore,
      we compared the characteristics of lymphocytes derived from the spleens and
      granulomas of Schistosoma mansoni-infected mice during the course of their
      disease. We examined lymphocyte cell cycle kinetics, migration, expression of
      activation Ags (CD69 and IL-2R), cytokine production (IL-2, IL-4, IFN-gamma), and
      apoptosis. Lymphocytes in the G2/M phase of the cell cycle and high levels of
      lymphocyte intracellular IL-2 were found in the spleen but not in the granuloma.
      Cell trafficking experiments showed Ag-specific recruitment of schistosomal egg
      Ag (SEA)-reactive lymphoblasts into granulomas in vivo, as well as recruitment
      to, residence within, and egress from granulomas in vitro. Granuloma-derived
      lymphocytes were more highly activated than splenic lymphocytes based on higher
      levels of CD69 and IL-2R expression. While the granuloma microenvironment was
      rich in Th2 cytokines, during peak granuloma formation, the lymphocytes per se
      from the spleen and granuloma did not exhibit a dominant Th1 or Th2 cytokine
      profile, producing low but similar levels of IL-4 and IFN-gamma. The discrepancy
      between high IL-2R expression and low levels of IL-2 protein production by
      granuloma lymphocytes was associated with increased apoptosis in the granuloma
      compared with the spleen. These findings support the hypothesis that granulomas
      may play a role in the regulation of systemic pathology in schistosomiasis by
      adversely affecting the survival of SEA-reactive, immunopathogenic T lymphocytes.

PMID- 9780184
TI  - Nitric oxide prevents IL-1beta and IFN-gamma-inducing factor (IL-18) release from
      macrophages by inhibiting caspase-1 (IL-1beta-converting enzyme).
AB  - Procytokine processing by caspase-1 is required for the maturation and release of
      IL-1beta and IFN-gamma-inducing factor (IGIF) (or IL-18) from activated
      macrophages (Mphi). Nitric oxide (NO) has emerged as a potent inhibitor of
      cysteine proteases. Here, we tested the hypothesis that NO regulates cytokine
      release by inhibiting IL-1beta-converting enzyme (ICE) or caspase-1 activity.
      Activated RAW264.7 cells released four to five times more IL-1beta, but not TNF
      alpha, in the presence of the NO synthase inhibitor N(G)-monomethyl-L-arginine.
      Stimulated peritoneal Mphi from wild-type mice (inducible NO synthase (iNOS)+/+)
      also released more IL-1beta if exposed to N(G)-monomethyl-L-arginine, whereas
      Mphi from iNOS knockout mice (iNOS-/-) did not. Inhibition of NO synthesis in
      stimulated RAW264.7 cells also resulted in a threefold increase in intracellular
      caspase-1 activity. The NO donor S-nitroso-N-acetyl-DL-penicillamine inhibited
      caspase-1 activity in cells as well as the activity of purified recombinant
      caspase-1 and also prevented the cleavage of pro-IL-1beta and pro-IGIF by
      recombinant caspase-1. The inhibition of caspase-1 by NO was reversible by the
      addition of DTT, which is consistent with S-nitrosylation as the mechanism of
      caspase-1 inhibition. An in vivo role for the regulation of caspase-1 by NO was
      established in iNOS knockout animals, which exhibited significantly higher plasma
      levels of IL-1beta and IFN-gamma than their wild-type counterparts at 10 h
      following LPS injection. Taken together, these data indicate that NO suppresses
      IL-1beta and IGIF processing by inhibiting caspase-1 activity, providing evidence
      for a unique role for induced NO in regulating IL-1beta and IGIF release.

PMID- 9780186
TI  - Down-regulation of tumoricidal NK and NK T cell activities by MHC Kb molecules
      expressed on Th2-type gammadelta T and alphabeta T cells coinfiltrating in early
      B16 melanoma lesions.
AB  - We examined whether gammadelta T and alphabeta T cells accumulating in early B16
      melanoma lesions regulate NK and NK T cells that attack tumor cells. Freshly
      isolated and cultured tumor-infiltrating lymphocyte (TIL) populations of NK and
      NK T cells lysed B16 and produced IFN-gamma, whereas gammadelta T and a large
      part of alphabeta T cell populations had no substantial cytotoxicity against B16
      and secreted Th2 cytokines. Furthermore, the freshly isolated NK1.1+ TIL
      population exhibited a higher anti-B16 effect than did splenocytes. Gammadelta T
      and alphabeta T cell populations dramatically inhibited the cytotoxicity of NK
      and NK T cells in an MHC Kb-dependent manner. Culture supernatant from gammadelta
      T and alphabeta T cell populations inhibited the proliferation of NK and NK T
      cell populations but did not affect their cytotoxicity, suggesting that the
      released Th2 cytokines are merely partly involved in the down-modulation of NK
      lineage cells. NK1.1+ cells obtained from TIL of gammadelta T cell-depleted mice
      significantly lysed B16 cells compared with those from control mice. Finally,
      anti-Kb Fab mAb injected intralesionally at an early, but not at a late, stage of
      development of B16 melanoma inhibited tumor growth. These findings suggest that
      Th2-type gammadelta T and alphabeta T cells infiltrating in early B16 development
      inhibit the tumoricidal activity of NK-lineage cells using their class I
      molecules and partly their suppressive cytokines.

PMID- 9780187
TI  - Heat-killed Listeria monocytogenes as an adjuvant converts established murine Th2
      dominated immune responses into Th1-dominated responses.
AB  - We investigated the capacity of heat-killed Listeria monocytogenes (HKL), a
      potent stimulator of the innate immune system, as a vaccine adjuvant to modify
      both primary and secondary Ag-specific immune responses. Mice immunized with the
      Ag keyhole limpet hemocyanin (KLH) mixed with HKL generated a KLH-specific
      primary response characterized by production of Th1 cytokines and large
      quantities of KLH-specific IgG2a Ab. Moreover, administration of KLH with HKL as
      an adjuvant reversed established immune responses dominated by the production of
      Th2 cytokines and high levels of KLH-specific IgE and induced a Th1-type response
      with high levels of IFN-gamma and IgG2a and low levels of IgE and IL-4.
      Neutralization of IL-12 activity at the time of HKL administration blocked the
      enhancement of IFN-gamma and reduction of IL-4 production, indicating that IL-12,
      induced by HKL, was responsible for the adjuvant effects on cytokine production.
      These results suggest that HKL as an adjuvant during immunization can
      successfully bias the development of Ag-specific cytokine synthesis toward Th1
      cytokine production even in the setting of an ongoing Th2-dominated response.
      Thus, HKL may be clinically effective in vaccine therapies for diseases such as
      allergy and asthma, which require the conversion of Th2-dominated immune
      responses into Th1-dominated responses.

PMID- 9780188
TI  - Blockade of CTLA-4 enhances host resistance to the intracellular pathogen,
      Leishmania donovani.
AB  - CTLA-4 has recently been shown to act as a negative regulator of T cell
      activation. Here we provide evidence that blockade of CTLA-4 can result in
      enhanced host resistance to an intracellular pathogen. The administration of anti
      CTLA-4 mAb 4F10 to BALB/c mice, 1 day following infection with Leishmania
      donovani, enhanced the frequency of IFN-gamma and IL-4 producing cells in both
      spleen and liver, and dramatically accelerated the development of a hepatic
      granulomatous response. The expression of mRNA for the CXC chemokine gammaIP-10
      was also elevated above that seen in control Ab treated mice, and was directly
      correlated with the frequency of IFN-gamma producing cells. In contrast,
      macrophage inflammatory protein-1alpha (MIP-1alpha) and monocyte chemotactic
      protein-1 (MCP-1) mRNA levels were unaffected by anti-CTLA-4 treatment,
      suggesting that CTLA-4 blockade may exert selective effects on chemokine
      expression. These changes in tissue response and cytokine/chemokine production
      were accompanied by a 50 to 75% reduction of parasite load in the spleen and
      liver of anti-CTLA-4-treated animals compared to controls. Furthermore,
      administration of anti-CTLA-4 mAb 15 days after L. donovani infection, when
      parasite burden is increasing in both organs, also resulted in enhanced
      resistance. Thus, these studies indicate a potent immunomodulatory and
      potentially therapeutic role for interventions targeted at CTLA-4.

PMID- 9780189
TI  - Dermal endothelial cells and keratinocytes produce IL-7 in vivo after human
      Schistosoma mansoni percutaneous infection.
AB  - The parasite Schistosoma mansoni infects its definitive mammalian host through an
      obligatory cutaneous penetration. In this work, we studied early immune response
      following migration of larvae through human skin, the first immunocompetent organ
      encountered by the parasite. For this purpose we used an experimental model of
      severe combined immunodeficient mice engrafted with human skin and injected with
      autologous PBL. Six days after percutaneous infection, we observed an
      infiltration of lymphocytes within the human skin, predominantly composed of CD4+
      T cells. Moreover, among the cytokines potentially present in the infected skin,
      immunohistochemistry analysis revealed an in vivo expression of IL-7 in the
      epidermal layers and strikingly at the level of vascular endothelium. Using an in
      vitro coculture system, we showed that the S. mansoni larvae directly trigger IL
      7 production by human dermal microvascular endothelial cells but not by
      keratinocytes. Finally, measurements of IL-7 concentrations in plasma of 187 S.
      mansoni-infected individuals showed that the youngest, which are also the most
      infected, displayed the highest IL-7 levels. Together, these findings describe
      dermal endothelial cells as a novel source of IL-7, a cytokine particularly
      important in schistosomiasis.

PMID- 9780190
TI  - Peripheral blood-derived CD34+ progenitor cells: CXC chemokine receptor 4 and CC
      chemokine receptor 5 expression and infection by HIV.
AB  - The present study demonstrates cell surface expression of both CXC chemokine
      receptor 4 (CXCR4) and CC chemokine receptor 5 (CCR5), major coreceptors for T
      cell-tropic and macrophage-tropic strains of HIV, respectively, on CD34+
      progenitor cells derived from the peripheral blood. CD34+ progenitor cells were
      susceptible to infection by diverse strains of HIV, and infection could be
      sustained for prolonged periods in vitro. HIV entry into CD34+ progenitor cells
      could be modulated by soluble CD4, HIV gp120 third variable loop neutralizing mAb
      and the cognate ligands for the CXCR4 and CCR5 HIV coreceptors. This study
      suggests that a significant proportion of the circulating progenitor cell pool
      may serve as a reservoir for HIV that is capable of trafficking the virus to
      diverse anatomic compartments. Furthermore, the infection and ultimate
      destruction of these progenitor cells may explain in part the defective
      lymphopoiesis in certain HIV-infected individuals despite effective control of
      virus replication during highly active antiretroviral therapy.

PMID- 9780191
TI  - Haemophilus influenzae type b polysaccharides-protein conjugate vaccine elicits a
      more diverse antibody repertoire in infants than in adults.
AB  - Conjugation of bacterial polysaccharides (PS) to protein carriers confers the
      ability to elicit protective serum Ab in infants, who respond poorly to plain PS.
      The serum Ab of young children immunized with Haemophilus influenzae type b (Hib)
      PS conjugate vaccine varies with age and Ag formulation. To understand these age
      related changes in human anti-Hib PS immune responses we determined the variable
      region gene sequences encoding anti-Hib PS mAbs of infants immunized with Hib
      oligosaccharide-diphtheria toxin vaccine. The anti-Hib PS repertoire of children
      differs from that of adults. A smaller proportion of mAbs from children have high
      affinity for Hib PS, and the overall variable region gene repertoire of infants
      is more diverse than that in adults. Variable region genes encoding high affinity
      mAbs of infants are similar to the restricted repertoire described in adults. Low
      affinity anti-Hib PS mAbs of infants are encoded by a heterogeneous group of
      genes that are uncommonly observed in the adult repertoire. Abs with high
      affinity for Hib PS from infants, like most mAbs from adults, react only with Hib
      PS and the structurally similar PS of Escherichia coli K100, whereas low affinity
      mAbs of infants are polyreactive. The low affinity anti-Hib PS mAbs of infants
      immunized with Hib oligosaccharide-diphtheria toxin vaccine vaccine are not
      reflected in serum Ab. However, the differences between the variable region gene
      repertoires of adults and infants may account for the distinct immunologic
      characteristics of the anti-Hib PS responses in young children immunized with
      other vaccine formulations.

PMID- 9780192
TI  - Functional dissociation between local and systemic immune response during anti
      melanoma peptide vaccination.
AB  - Peptide vaccination against tumor Ags can induce powerful systemic CTL responses.
      However, in the majority of patients, no tumor regression is noted. To study this
      discrepancy, we analyzed CTL reactivity in a melanoma patient (F001) vaccinated
      with g209-2M peptide, a single residue variant of gp100(209-217). G209/g209-2M
      reactive CTL were identified in post- but not prevaccination PBL. Limiting
      dilution analysis identified one predominant CTL clone (C1-35), with TCR
      Vbeta6s2, recognizing g209/HLA-A*0201-expressing targets. Additionally, two
      autologous melanoma lines (F001TU-3 and -4) and 20 separate tumor-infiltrating
      lymphocyte cultures were generated from a fine needle aspirate of a metastatic
      lesion progressing after initial response to vaccination. Both F001TU did not
      express gp100 and were not recognized by C1-35. Loss of gp100 by F001TU
      correlated with a marked reduction of gp100 expression in the same metastatic
      lesion compared with prevaccination. Thus, ineffectiveness of C1-35 and tumor
      progression could be best explained by loss of target Ag expression.
      Interestingly, 12 of 20 tumor-infiltrating lymphocyte cultures recognized F001TU,
      but none demonstrated g209/g209-2M reactivity, suggesting a functional
      dissociation between systemic and local immune response. This study suggests that
      vaccination effects must be analyzed in the target tissue, rather than in the
      systemic circulation alone.

PMID- 9780193
TI  - Weak anamnestic responses of inbred mice to Yersinia F1 genetic vaccine are
      overcome by boosting with F1 polypeptide while outbred mice remain nonresponsive.
AB  - The role of immunity to intracellular Ags in resistance to infection by Yersinia
      is not well established. The enteropathogenic bacteria Yersinia
      pseudotuberculosis and Yersinia enterocolitica actively translocate Ags to the
      cytosol of eukaryotic cells. Whereas Yersinia pestis does not always express the
      requisite cellular adhesins, results have varied as to whether similar cytosolic
      translocation of Ags occurs in vitro. We used a genetic vaccine to induce
      intracellular expression of the fraction 1 (F1) capsular protein of Y. pestis
      within host mammalian cells and examined the ensuing immune response. The F1
      genetic vaccine stimulated only weak CTL responses in BALB/c mice. Substantial Ab
      responses to the F1 genetic vaccine were obtained in all inbred strains of mice
      tested, but Ab levels were less than those resulting from vaccination with the F1
      polypeptide. In contrast, outbred mice did not respond to the F1 plasmid,
      suggesting that some inbred mouse strains may exhibit exaggerated responses to
      plasmid vaccines. A primary immunization with the F1 genetic vaccine followed by
      a boost with recombinant F1 polypeptide produced a vigorous Ab response from
      inbred mice that was equivalent to three injections of F1 polypeptide. We
      conclude that cytosolic expression of the F1 Ag efficiently primes immunity,
      while secondary exposure to the F1 polypeptide is required for optimal Ab
      induction.

PMID- 9780194
TI  - IFN-gamma, IL-12, and TNF-alpha are required to maintain reduced liver pathology
      in mice vaccinated with Schistosoma mansoni eggs and IL-12.
AB  - The development of hepatic fibrosis and portal hypertension is the principal
      cause of morbidity and mortality in schistosomiasis mansoni. Nevertheless,
      relatively little is known about the mechanisms that lead to excessive collagen
      deposition during infection with Schistosoma mansoni. In the murine model,
      infection leads to significant egg-induced granuloma formation, tissue
      eosinophilia, and hepatic fibrosis. The pathology has been linked to dominant
      type 2 cytokine expression, and our recent studies showed that sensitizing
      animals to egg Ags in combination with IL-12, before infection, led to a highly
      significant reduction in egg-induced immunopathology. In this study, we
      demonstrate that in contrast with egg/IL-12-sensitized animals that showed marked
      decreases in pathology, mice similarly sensitized but depleted of IFN-gamma, IL
      12, or TNF-alpha at the time of egg laying developed granulomas that were similar
      to the non-IL-12-treated control group. Although all three anti-cytokine-treated
      groups exhibited a dominant type 1 response in lymph node cells restimulated ex
      vivo, the expression of type 2 cytokine mRNA was markedly restored at the site of
      granuloma formation, which suggests that all three cytokines are required to
      maintain the suppressed type 2 pattern. Moreover, egg/IL-12-sensitized mice
      depleted of IFN-gamma or IL-12 displayed a partial reduction in IFN-gamma
      production, suggesting that multiple type 1 cytokines were required to maintain
      polarized type 1 responses to chronic type 2-inducing stimuli. Together, these
      data reveal key roles for IFN-gamma, IL-12, and TNF-alpha in the protective
      effects mediated by this IL-12-based vaccine to prevent pathology.

PMID- 9780195
TI  - Comparison of humoral immune responses elicited by DNA and protein vaccines based
      on merozoite surface protein-1 from Plasmodium yoelii, a rodent malaria parasite.
AB  - Immunization with DNA vaccines encoding relevant Ags can induce not only cell
      mediated immune response but also humoral immune responses against pathogenic
      microorganisms in several animal models. Our previous results demonstrated that,
      when the C terminus (PyC2) of Plasmodium yoelii merozoite surface protein-1 (MSP
      1), a leading vaccine candidate against erythrocytic stages of malaria, was
      expressed as a fusion protein (GST-PyC2) with glutathione S-transferase (GST), it
      elicited Ab-mediated protective immune responses in BALB/c mice. In our present
      study, we wished to examine the humoral responses to a DNA vaccine (V3) encoding
      GST-PyC2. The GST-PyC2 expressed in V3-transfected Cos 7 cells was recognized by
      a protective monoclonal Ab to PyC2 (mAb302), although the secreted product had
      undergone N-linked glycosylation. When BALB/c mice were immunized with V3
      plasmid, anti-PyC2 Abs were successfully induced. These Abs immunoprecipitated
      native PyMSP-1 protein and competed with mAb302 for binding to its epitope at a
      level similar to those elicited by GST-PyC2 protein immunization. However, these
      Abs had significantly lower titers and avidities, and different isotype profiles
      and protective capacities against a lethal erythrocytic stage challenge, than
      those resulting from immunization with GST-PyC2 protein. Most surprising was the
      finding that, in contrast to protein immunization, there was no significant
      increase in the avidity of either GST-specific or PyC2-specific IgG Abs during
      the course of DNA immunization. This suggests that there may be little or no
      affinity maturation of specific Abs during DNA immunization in this system.

PMID- 9780196
TI  - Apoptosis of epithelial cells and macrophages due to infection with the obligate
      intracellular pathogen Chlamydia psittaci.
AB  - We have characterized the cytotoxic activity of the obligate intracellular
      bacterium Chlamydia psittaci, which resides within a membrane-bound vacuole
      during the 2-day infection cycle. We have established that infected epithelial
      cells and macrophages die through apoptosis, which is measurable within 1 day of
      infection and requires productive infection by the bacteria. Inhibition of host
      cell protein synthesis has no effect on cell death, but blocking bacterial entry
      or bacterial protein synthesis prevents apoptosis, implying that bacterial growth
      is required for death of the host cell. Apoptosis was confirmed through the use
      of electron microscopy, terminal deoxynucleotidyl transferase-mediated dUTP nick
      end labeling, gel agarose electrophoresis of fragmented DNA, and propidium-iodide
      labeling of host cell nuclei. Although infected cells died preferentially, both
      infected and uninfected cells became apoptotic, suggesting that the infected
      cells may secrete proapoptotic factors. Inhibition of either of two proapoptotic
      enzymes, caspase-1 or caspase-3, did not significantly affect Chlamydia-induced
      apoptosis. These results suggest that, as in the case of apoptosis due to Bax
      expression or oncogene dysregulation, which initiate the apoptotic program within
      the cell interior, the Chlamydia infection may trigger an apoptotic pathway that
      is independent of known caspases. As apoptotic cells secrete proinflammatory
      cytokines, Chlamydia-induced apoptosis may contribute to the inflammatory
      response of the host.

PMID- 9780197
TI  - The memory B cell subset responsible for the secretory IgA response and
      protective humoral immunity to rotavirus expresses the intestinal homing
      receptor, alpha4beta7.
AB  - Infection of mice with murine rotaviruses induces life-long immunity,
      characterized by high levels of IgA in the intestine and large numbers of
      rotavirus (RV)-specific Ab-secreting cells in gut-associated lymphoid tissues.
      Lymphocyte trafficking into gut-associated lymphoid tissues is mediated by
      interaction of the alpha4beta7 integrin on lymphocytes with the vascular mucosal
      addressin cell adhesion molecule-1. To determine whether B cell memory for RV
      correlates with alpha4beta7 expression, we transferred sorted B220+
      phenotypically defined memory (IgD- alpha4beta7(high) and IgD- alpha4beta7-) and
      naive (IgD+ alpha4beta7+) splenocytes into recombination-activating gene-2
      knockout mice (B and T cell-deficient) that were chronically infected with RV.
      Only mice receiving alpha4beta7(high) memory (IgD-) B cells produced RV-specific
      IgA in the stool, cleared the virus, and were immune to reinfection.
      Alpha4beta7(high) (but not alpha4beta7-) memory B cells from donors boosted as
      much as 7 mo previously also cleared the virus, indicating that alpha4beta7(high)
      memory B cells maintain long term functional immunity to RV. Although only
      alpha4beta7(high) memory cells provided mucosal immunity, alpha4beta7- cells from
      recently boosted donor animals could generate RV-specific serum IgG, but, like
      naive (IgD+) B cells, were unable to induce viral clearance even 60 days after
      cell transfer. These data indicate that protective immunity for an intestinal
      pathogen, RV, resides in memory phenotype B cells expressing the intestinal
      homing receptor, alpha4beta7.

PMID- 9780198
TI  - CC-3052: a water-soluble analog of thalidomide and potent inhibitor of activation
      induced TNF-alpha production.
AB  - The immunomodulatory drug thalidomide has been shown to be clinically useful in a
      number of situations due to its ability to inhibit TNF-alpha synthesis. However,
      its use is restricted by potentially serious side effects, including
      teratogenicity and neuorotoxicity; furthermore, insolubility may present problems
      in terms of systemic bioavailability. Recently, structural modifications of
      thalidomide have been designed enabling greatly enhanced anti-TNF-alpha activity
      in LPS-treated mice. In contrast to thalidomide (LPS-induced TNF-alpha IC50
      approximately 200 microM in DMSO) and other analogs tested, one of these
      compounds, CC-3052 (IC50 approximately 1 microM in water), is water soluble.
      Furthermore, this analog exhibits increased stability in human plasma (t(1/2)
      approximately 17.5 vs 1.5 h for thalidomide) and appears to be nontoxic,
      nonmutagenic, and nonteratogenic. At pharmacologically active levels, cellular
      proliferation and LPS-induced IL-6 mRNA and IL-12p40 mRNA (as well as IL-1beta
      and IL-6 protein levels) in whole blood cultures were not affected; apparent
      inhibition of NK activity by CC-3052 was reversed upon addition of exogenous rTNF
      alpha. In addition, IL-10 mRNA and protein levels were increased. These
      properties are consistent with results indicating inhibition of phosphodiesterase
      type IV activity by CC-3052. Furthermore, CC-3052 did not increase the
      degradation rate of macrophage TNF-alpha transcripts nor inhibit LPS-induced
      primary macrophage NF-kappaB activation. Taken together, the potency of selective
      TNF-alpha inhibition, water solubility, and increased plasma stability make CC
      3052 an excellent candidate for further development and clinical evaluation for
      the treatment of TNF-alpha-mediated disease.

PMID- 9780199
TI  - Soluble CD14(1-152) confers responsiveness to both lipoarabinomannan and
      lipopolysaccharide in a novel HL-60 cell bioassay.
AB  - CD14 is a pattern recognition receptor involved in the interaction with multiple
      ligands, including LPS from gram-negative bacteria and lipoarabinomannan (LAM)
      from mycobacteria. While the interactions between LPS and soluble CD14 (sCD14)
      have been analyzed in detail, LAM/CD14 interactions remain uncharacterized due to
      the lack of suitable functional assays. We describe herein a novel bioassay for
      the analysis of CD14/ligand interactions. CD14-negative myeloid HL-60 cells up
      regulate endogenous CD14 gene expression when stimulated with LPS in the presence
      of recombinant soluble CD14(1-348). Using the HL-60 bioassay, we showed that
      sCD14(1-348) confers responsiveness not only to LPS, but also to LAM. The
      response to LAM, but not that to LPS, was highly dependent on LPS binding protein
      (LBP). The N-terminal half of CD14 was sufficient to mediate HL-60 responses to
      LAM, since HL-60 cells responded with similar efficiency when stimulated with LAM
      and LBP in the presence of sCD14(1-348) or sCD14(1-152). Thus, the N-terminal 152
      amino acids of CD14 contain the site(s) involved in the interaction with LAM and
      LBP, as well as the residues required for LAM-dependent CD14 signaling.

PMID- 9780200
TI  - Thymic expression of the transcription factor Nur77 rescues the T cell but not
      the B cell abnormality of gld/gld mice.
AB  - Fas and Fas ligand are critical regulators of lymphocyte homeostasis. Disruption
      of this pathway in the spontaneous mouse mutant gld leads to autoimmunity
      characterized by the appearance of a population of CD4- 8- B220+ T cells and the
      production of autoantibodies. Nur77 is a transcription factor that is induced
      upon TCR signaling. Constitutive thymic expression of Nur77 leads to apoptosis.
      We have previously shown that introduction of this Nur77 transgene can eliminate
      the accumulation of abnormal T cells in the periphery of gld/gld mice. In this
      report, we further characterized the effects of the Nur77 transgene on the gld
      phenotype. Nur77-mediated apoptosis is evident in the thymuses of mice with
      either a gld/gld homozygous or gld/+ heterozygous background. Consequently, few
      mature T cells are generated in these mice. In addition, mature T cells exhibit a
      diminished response to proliferative signals through CD3. Interestingly, the
      Nur77 transgene failed to reduce serum levels of Igs and anti-DNA Abs to wild
      type levels. These data suggest that the rescue of the T cell lymphoproliferative
      syndrome in gld/gld mice by the Nur77 transgene is mediated by events in the
      thymus and that B cell autoimmune disease associated with the gld mutation can
      develop independently of the T cell abnormality.

PMID- 9780202
TI  - Oleic acid increases cell surface expression and activity of CD11b on human
      neutrophils.
AB  - Traumatic bone injury frequently results in the release of marrow-derived fatty
      material into the circulation. This may lead to the syndrome of fat embolism,
      associated with the generation of free fatty acids, the sequestration of
      neutrophils in the lungs, and the subsequent development of acute respiratory
      distress. Neutrophil accumulation in tissues requires their adherence to vascular
      endothelial cells and involves the beta2 integrin, CD11b/CD18 (Mac-1). We now
      report that the exposure of isolated human neutrophils to oleic acid causes a
      rapid increase in the cell surface expression and affinity state of CD11b,
      particularly under acidic conditions that are typical of inflammatory sites.
      Oleic acid also triggers neutrophil aggregation and neutrophil adherence to both
      fibrinogen-coated surfaces and confluent cultures of HUVEC. These processes are
      blocked by CD11b-specific inhibitors, including neutrophil-inhibitory factor and
      mAbs to CD11b. These observations may help explain the etiology of so-called fat
      embolism wherein trauma-induced release of fatty material causes pulmonary
      neutrophil accumulation and the development of acute respiratory distress.

PMID- 9780201
TI  - Chronically HIV-1-infected monocytic cells induce apoptosis in cocultured T
      cells.
AB  - We have previously developed a human macrophage hybridoma model system to study
      the effect of HIV-1 infection on monocytic function. Upon coculture of one
      chronically (35 days postinfection) HIV-1-infected human macrophage hybridoma
      cell line, 43HIV, there was a dose-dependent decrease in the viability of
      cocultured Ag-stimulated T cells associated with an increase in DNA strand
      breaks. Enhanced apoptosis was determined by labeling with biotinylated dUTP and
      propidium iodide, increased staining with annexin V, increased side light scatter
      and expression of CD95, and decreased forward light scatter and expression of Bcl
      2. There was also increased DNA strand breaks as determined by propidium iodide
      staining in unstimulated T cells cocultured with 43HIV and in T cells stimulated
      with anti-CD3 mAb and PHA. Pretreatment with 5145, a human polyclonal anti-gp120
      Ab that recognizes the CD4 binding region, as well as with an anti-Fas ligand mAb
      blocked apoptosis in CD4+ T cells but not in CD8+ T cells. A soluble factor with
      a Mr below 10,000 Da was defined that induced apoptosis in CD4+ and CD8+ T cells
      and B cells. SDS-PAGE analysis of the active fractions revealed a band of 6000 Da
      that, after electroelution, had proapoptotic activity. The pI of the activity was
      estimated to be between 6.5 and 7.0. In conclusion, chronically HIV-1-infected
      monocytic cells induce apoptosis in bystander-, Ag-, anti-CD3-, and mitogen
      stimulated T cells by multiple factors, which may contribute to the depletion of
      lymphocytes induced by HIV-1.

PMID- 9780203
TI  - Expression and participation of eotaxin during mycobacterial (type 1) and
      schistosomal (type 2) antigen-elicited granuloma formation.
AB  - Eotaxin participation was analyzed during types 1 and 2 lung granuloma formation
      induced by embolizing Sepharose beads coupled to purified protein derivative
      (PPD) of Mycobacterium bovis or soluble Ags derived from Schistosoma mansoni
      eggs. Eotaxin was monitored by protein ELISA and semiquantitative reverse
      transcriptase PCR mRNA analysis. Both types 1 and 2 granulomas released eotaxin,
      but levels were sixfold greater (on day 4) in the type 2 than for the type 1 or
      foreign body granulomas. Transcripts for eotaxin, IL-4, and CCR3 (eotaxin
      receptor) were also enhanced during type 2 granuloma formation. Anti-IL-4
      treatment impaired eotaxin mRNA in lungs with type 2 granulomas, indicating that
      IL-4 promoted local eotaxin expression. In vivo, anti-eotaxin treatment caused
      modest reductions in the size of both types 1 and 2 lesions, with negligible
      effect on eosinophil recruitment. Surprisingly, anti-eotaxin treatment abrogated
      IFN-gamma-producing cells in regional lymph nodes during the type 1 PPD response.
      Lymph nodes draining both types 1 and 2 lesions showed enhanced CCR3 mRNA, but
      this followed the time of maximum eotaxin protein and mRNA expression.
      Correlative, in vitro studies revealed that graded doses of eotaxin increased IFN
      gamma production from PPD-sensitive regional lymph node cultures, while monocyte
      chemotactic protein-1, an important macrophage chemoattractant, had the opposite
      effect. These findings indicate that eotaxin expression is not limited to type 2
      hypersensitivity granulomas, but also promotes IFN-gamma production during
      mycobacterial responses.

PMID- 9780204
TI  - Immunoregulatory roles of IL-10 in innate immunity: IL-10 inhibits macrophage
      production of IFN-gamma-inducing factors but enhances NK cell production of IFN
      gamma.
AB  - In our study of the immunoregulatory roles of IL-10 in innate immunity,
      nonantigenic phagocytosable chitin particles were administered i.v. to IL-10
      deficient (knockout (KO)) mice or KO mice pretreated with anti-NK1.1 or anti-IFN
      gamma Abs. The results established that chitin treatment of KO mice increased
      superoxide anion release from alveolar macrophages (Mphi) to a level much higher
      than that in wild-type (WT) mice. The results also suggested that the NK cell is
      the source of IFN-gamma that is primarily responsible for this alveolar Mphi
      priming. To further study the roles of IL-10-inhibiting chitin-induced IFN-gamma
      production, we used spleen cell cultures. The experiments showed that IL-12, IL
      18, and TNF-alpha, which were produced by chitin-stimulated Mphi, contributed to
      the IFN-gamma-inducing activity of chitin. Our results established that exogenous
      IL-10 inhibited chitin-induced IFN-gamma production in spleen cell cultures from
      both KO and WT mice. Exogenous IL-10 also inhibited IL-12 and TNF-alpha
      production by chitin-stimulated Mphi. Exogenous IL-10 decreased IL-12- or IL-18
      induced IFN-gamma levels in KO but not in WT NK cell cultures. However, exogenous
      IL-10 enhanced IFN-gamma levels when NK cells were stimulated simultaneously with
      both IL-12 and IL-18 in KO and WT cultures. Our in vitro data indicate that IL-10
      has differential effects on chitin-induced IFN-gamma production. However, the
      inhibitory effects of endogenous IL-10 appear to be dominant in the chitin
      induced alveolar Mphi priming response in vivo.

PMID- 9780205
TI  - Virus-induced immunoinflammatory lesions in the absence of viral antigen
      recognition.
AB  - Herpetic stromal keratitis (HSK) is a CD4+ T cell-controlled immunopathologic
      lesion in the eye that results from infection with herpes simplex virus (HSV).
      Target Ags involved in HSK remain undefined. In this study, we determined if HSK
      could be induced in animals genetically incapable of generating HSV Ag-specific
      CD4+ T cells. Mice bearing transgenic TCR specific to OVA peptide 323-339
      (DO11.10) were crossed to SCID mice whose offspring (Tg-SCID) possessed CD4+ T
      cells, >98% of which expressed the OVA peptide-specific TCR. HSV infection of Tg
      SCID mice was lethal, and mice failed to generate detectable T cell responses
      even after repeated immunization with a mutant avirulent virus (AN-1).
      Immunization with AN-1 virus followed by ocular challenge with HSV resulted in
      ocular inflammation before encephalitis, in contrast to the protection conferred
      in the control BALB/c and DO11.10 mice. These results indicate that clinical HSK
      may not require viral Ag recognition by CD4+ T cells and that T cells of
      irrelevant specificity can be recruited, activated, and driven into effector
      function in the HSV-infected cornea. This is suggested to represent a bystander
      activation effect resulting from the presence of proinflammatory mediators
      resulting from HSV replication.

PMID- 9780206
TI  - Effect of cytotoxic necrotizing factor-1 on actin cytoskeleton in human
      monocytes: role in the regulation of integrin-dependent phagocytosis.
AB  - Cytotoxic necrotizing factor-1 (CNF1) is isolated from pathogenic strains of
      Escherichia coli and catalyzes the activation of Rho GTPases by the deamidation
      of a glutamine residue. This toxin induces stress fiber formation, cell
      spreading, and membrane folding and promotes phagocytosis competence in
      epithelial cells. We show that CNF1 induces morphologic changes in monocytic
      cells: polarized-like shape in THP-1 cells, lamellipodia, and cell spreading in
      adherent monocytes. CNF1 also increased filamentous actin (F-actin) content in a
      time- and dose-dependent manner. In addition, the toxin profoundly reorganized
      the actin cytoskeleton: redistribution of F-actin in polarized deformations of
      THP-1 cells and disorganization of microfilament network in monocytes. We also
      studied the effects of CNF1 on phagocytosis. It markedly impaired the ingestion
      of unopsonized zymosan involving CR type 3. However, CNF1 had no effect on the
      uptake of iC3b-coated zymosan or IgG-mediated phagocytosis of SRBC. In addition,
      CNF1 induced clustering of CR3 and Fc gammaRII (CD32) but selectively impaired
      the colocalization of CR3 with F-actin. It is likely that CNF1-induced
      reorganization of actin cytoskeleton down-modulates integrin activation-dependent
      phagocytosis by preventing the codistribution of CR3 with F-actin. CNF1 may
      control some features of integrin-dependent phagocytosis in myeloid cells through
      its action on Rho GTP binding proteins and cytoskeletal organization.

PMID- 9780207
TI  - HIV-1 envelope gp120 inhibits the monocyte response to chemokines through CD4
      signal-dependent chemokine receptor down-regulation.
AB  - Since HIV-1 infection results in severe immunosuppression, and the envelope
      protein gp120 has been reported to interact with some of the chemokine receptors
      on human T lymphocytes, we postulated that gp120 may also affect monocyte
      activation by a variety of chemokines. This study shows that human peripheral
      blood monocytes when preincubated with gp120 either purified from laboratory
      adapted strains or as recombinant proteins exhibited markedly reduced binding,
      calcium mobilization, and chemotactic response to chemokines. The gp-120
      pretreated monocytes also showed a decreased response to FMLP. This broad
      inhibition of monocyte activation by chemoattractants required interaction of
      gp120 with CD4, since the effect of gp120 was only observed in CD4+ monocytes and
      in HEK 293 cells only if cotransfected with both chemokine receptors and an
      intact CD4, but not a CD4 lacking its cytoplasmic domain. Anti-CD4 mAbs mimicked
      the effect of gp120, and both anti-CD4 Ab and gp120 caused internalization of
      CXCR4 in HEK 293 cells provided they also expressed CD4. Staurosporine blocked
      the inhibitory effect of gp120 on monocytes, suggesting that cellular signaling
      was required for gp120 to inhibit the response of CD4+ cells to chemoattractants.
      Our study demonstrates a broad suppressive effect of gp120 on monocyte activation
      by chemoattractants through the down-regulation of cell surface receptors. Thus,
      gp120 may be used by HIV-1 to disarm the monocyte response to inflammatory
      stimulation.

PMID- 9780209
TI  - Differential binding of IgG and of a HIV gp41 peptide by the B chain and A chain
      globular head sequences of C1q, respectively.
AB  - Two individual globular head regions (ghA and ghB) of the heterotrimeric C1q
      molecule (containing A, B, and C chains) were expressed in a bacterial expression
      system using a coproduction with the bacterial chaperone GroESL. The purified
      proteins were soluble and monomeric, as shown by gel-filtration analysis. No
      association into homotrimers was seen, which indicates that the ability to form
      heterotrimers is coupled with the discrimination against homotrimeric self
      association. The individual globular heads retained their binding activities
      toward two ligands bound by the whole C1q molecule, i.e., IgG and the peptide
      P(601-613) derived from the HIV envelope glycoprotein gp41. The differential
      binding activities displayed for these ligands indicated a degree of structural
      independence of the binding sites from the regions responsible for
      heterotrimerization. It was found, using single chain recombinant anti-C1q Abs,
      that the binding sites on C1q for IgG and gp41 do not overlap, and this
      observation is also consistent with the view that specialization between the C1q
      polypeptide chains takes place within the C1q molecule regarding their ligand
      binding activities.

PMID- 9780208
TI  - Factor Xa induces cytokine production and expression of adhesion molecules by
      human umbilical vein endothelial cells.
AB  - Proinflammatory effects induced by the serine protease factor Xa were
      investigated in HUVEC. Exposure of cells to factor Xa (5-80 nM) concentration
      dependently stimulated the production of IL-6, IL-8, and monocyte chemotactic
      protein-1 (MCP-1) and the expression of E-selectin, ICAM-1, and VCAM-1, which was
      accompanied by polymorphonuclear leukocyte adhesion. The effects of factor Xa
      were blocked by antithrombin III, but not by the thrombin-specific inhibitor
      hirudin, suggesting that factor Xa elicits these responses directly and not via
      thrombin. IL-1alpha and TNF-alpha were not implicated, since neither the IL-1
      receptor antagonist nor a TNF-neutralizing Ab could suppress the factor Xa
      responses. Active site-inhibited factor Xa and factor Xa depleted from gamma
      carboxyglutamic acid residues were completely inactive. The effector cell
      protease receptor-1 (EPR-1) seems not to be involved since anti-EPR-1 Abs failed
      to inhibit cytokine production. Moreover, neither the factor X peptide Leu83
      Leu88, representing the inter-epidermal growth factor sequence in factor Xa that
      mediates ligand binding to EPR-1, nor the peptide AG1, corresponding to the EPR-1
      sequence Ser123-Pro137 implicated in factor Xa binding, inhibited the factor Xa
      induced cytokine production. In conclusion, these findings indicate that factor
      Xa evokes a proinflammatory response in endothelial cells, which requires both
      its catalytic and gamma-carboxyglutamic acid-containing domain. The receptor
      system involved in these responses induced by factor Xa remains to be
      established.

PMID- 9780210
TI  - Ca2+-dependent production and release of IL-8 in human neutrophils.
AB  - IL-8, a potent neutrophil chemoattractant that is elevated about 200-fold in
      exudative neutrophils isolated from localized inflammatory sites in vivo, is
      thought to play a major role in recruitment of neutrophils to inflammatory sites.
      Incubation of peripheral blood neutrophils with thapsigargin, an inhibitor of the
      endoplasmic reticulum Ca2+-sequestering-ATPase, causes a dose-dependent induction
      of IL-8 synthesis that continues for up to 8 h. Cycloheximide inhibits the
      thapsigargin-induced IL-8 production, suggesting the induction of protein
      synthesis de novo. In addition, Northern blot analysis of mRNA isolated from
      neutrophils indicates that thapsigargin treatment increases IL-8 mRNA in a time-
      and dose-dependent manner. Thapsigargin also induces a biphasic rise in the
      intracellular Ca2+ concentration, [Ca2+]i, which is composed of an initial
      (within 15 s) EGTA-insensitive elevation in [Ca2+]i, followed by a delayed (2
      min) EGTA-sensitive component. Addition of EGTA before thapsigargin inhibited the
      induction of IL-8 production. Experiments in which EGTA was added at various
      times after thapsigargin treatment indicated that a sustained Ca2+ influx was
      required for maximum IL-8 production. Ascomycin and cyclosporin A, inhibitors of
      the Ca2+-dependent phosphatase, calcineurin, also inhibited thapsigargin-induced
      IL-8 production. Thus, in neutrophils, a prolonged increase in [Ca2+]i stimulates
      IL-8 transcription and synthesis, possibly through a calcineurin-dependent
      pathway.

PMID- 9780211
TI  - Interaction with secretory component stimulates effector functions of human
      eosinophils but not of neutrophils.
AB  - Eosinophils and their products are important in the pathophysiology of allergic
      inflammation in mucosal tissues. Secretory component bound to IgA mediates
      transepithelial transport of IgA and confers increased stability on the resultant
      secretory IgA; however, the effect of secretory component on the biologic
      activity of IgA is unknown. Here, we report that secretory IgA and secretory
      component preferentially activate human eosinophils. When eosinophils were
      stimulated with immobilized secretory IgA, degranulation and superoxide
      production were two- to threefold greater than when stimulated with serum IgA. In
      contrast, neutrophils responded similarly to secretory IgA and serum IgA. Flow
      cytometric analysis showed that eosinophils bound to purified secretory
      component. The binding of 125I-labeled secretory component was inhibited by
      unlabeled secretory component or secretory IgA but not by serum IgA. Superoxide
      production by eosinophils stimulated with cytokines or IgG was enhanced
      synergistically by immobilized secretory component; secretory component showed no
      effect on neutrophil activation. Finally, anti-CD18 mAb abolished eosinophil
      superoxide production stimulated with secretory IgA or secretory component but
      not with serum IgA, suggesting a crucial role for beta2 integrins in eosinophil
      interactions with secretory IgA or secretory component. Thus, secretory component
      plays important roles in activating eosinophil functions but not neutrophil
      functions. This preferential interaction between secretory component and
      eosinophils may provide a novel mechanism to regulate mucosal tissue
      inflammation.

PMID- 9780212
TI  - A chondroitin sulfate proteoglycan on human neutrophils specifically binds
      platelet factor 4 and is involved in cell activation.
AB  - Platelet factor 4 (PF-4), a member of the alpha-chemokine subfamily of cytokines,
      activates human neutrophils independently of intracellular free calcium
      mobilization or binding to IL-8R. In the present study, we have identified and
      partially characterized a receptor for PF-4 on human neutrophils, which displays
      weak cross-reactivity with the IFN-gamma-inducible protein 10, but not with other
      alpha-chemokines such as IL-8, neutrophil-activating peptide 2, or melanoma
      growth-stimulatory activity (GRO alpha). Binding studies revealed that human
      neutrophils express a high number of receptors (Bmax approximately 7.6 x 10(6)
      sites/cell) of moderate affinity (Kd approximately 650 nM). The kinetics of PF-4
      binding correlates with the proportion of PF-4 tetramers in solution and with the
      activation of neutrophils for exocytosis. Reduction of PF-4 binding and PF-4
      induced exocytosis in the presence of various glycosaminoglycans or following
      treatment of cells with chondroitinase ABC (but not other glycosaminoglycan
      degrading enzymes) altogether demonstrates that the PF-4 receptor is a
      proteoglycan of the chondroitin sulfate class. Cross-linking experiments with
      radiolabeled PF-4 revealed a receptor-ligand complex of approximately 250 kDa.
      Taken together, our data show that a distinct chondroitin sulfate proteoglycan
      represents specific receptors for tetrameric PF-4 on human neutrophils.

PMID- 9780213
TI  - Oxidized alpha2-macroglobulin (alpha2M) differentially regulates receptor binding
      by cytokines/growth factors: implications for tissue injury and repair mechanisms
      in inflammation.
AB  - Alpha2M binds specifically to TNF-alpha, IL-1beta, IL-2, IL-6, IL-8, basic
      fibroblast growth factor (bFGF), beta-nerve growth factor (beta-NGF), platelet
      derived growth factor (PDGF), and TGF-beta. Since many of these cytokines are
      released along with neutrophil-derived oxidants during acute inflammation, we
      hypothesize that oxidation alters the ability of alpha2M to bind to these
      cytokines, resulting in differentially regulated cytokine functions. Using
      hypochlorite, a neutrophil-derived oxidant, we show that oxidized alpha2M
      exhibits increased binding to TNF-alpha, IL-2, and IL-6 and decreased binding to
      beta-NGF, PDGF-BB, TGF-beta1, and TGF-beta2. Hypochlorite oxidation of
      methylamine-treated alpha2M (alpha2M*), an analogue of the proteinase/alpha2M
      complex, also results in decreased binding to bFGF, beta-NGF, PDGF-BB, TGF-beta1,
      and TGF-beta2. Concomitantly, we observed decreased ability to inhibit TGF-beta
      binding and regulation of cells by oxidized alpha2M and alpha2M*. We then
      isolated alpha2M from human rheumatoid arthritis synovial fluid and showed that
      the protein is extensively oxidized and has significantly decreased ability to
      bind to TGF-beta compared with alpha2M derived from plasma and osteoarthritis
      synovial fluid. We, therefore, propose that oxidation serves as a switch
      mechanism that down-regulates the progression of acute inflammation by
      sequestering TNF-alpha, IL-2, and IL-6, while up-regulating the development of
      tissue repair processes by releasing bFGF, beta-NGF, PDGF, and TGF-beta from
      binding to alpha2M.

PMID- 9780214
TI  - Mutations in the activation loop tyrosines of protein tyrosine kinase Syk
      abrogate intracellular signaling but not kinase activity.
AB  - The protein tyrosine kinase Syk plays a pivotal role in mediating the high
      affinity IgE receptor (Fc epsilonRI)-induced degranulation of mast cells. To
      examine the mechanism of Syk regulation, the two tyrosine residues at 519 and 520
      in the putative activation loop of rat Syk were mutated to phenylalanine either
      singly or in combination. The various mutants were expressed in a Syk-negative
      variant of the RBL-2H3 (rat basophilic leukemia 2H3) mast cell line. In these
      transfected cell lines, mutant Syk did show increased tyrosine phosphorylation in
      vivo and increased enzymatic activity in vitro after Fc epsilonRI aggregation.
      There were conformational changes detected by an Ab when the wild-type and mutant
      Syk were either tyrosine phosphorylated or bound to tyrosine-phosphorylated
      immunoreceptor tyrosine-based activation motif peptides. However, these mutant
      Syk were incapable of transducing Fc epsilonRI signaling. In cells in which the
      expression level of mutant Syk was similar to that of the wild-type Syk, Fc
      epsilonRI cross-linking induced no increase in cellular protein tyrosine
      phosphorylation, no increase in tyrosine phosphorylation of phospholipase C
      gamma2 and mitogen-activated protein kinase, and no histamine release.
      Overexpression of Y519F or Y520F Syk mutants partially reconstituted the
      signaling pathways. These results indicate that these tyrosines in the putative
      activation loop are not essential for the enzymatic activity of Syk or for the
      conformational changes induced by binding of tyrosine-phosphorylated
      immunoreceptor tyrosine-based activation motif peptides. However, these tyrosines
      are necessary for Syk-mediated propagation of Fc epsilonRI signaling.

PMID- 9780215
TI  - Products of sphingolipid catabolism block activation of the p21-activated protein
      kinases in neutrophils.
AB  - Neutrophils stimulated with the chemoattractant FMLP are known to exhibit a rapid
      and transient activation of two p21-activated protein kinases (Paks) with
      molecular masses of approximately 63 and 69 kDa. Paks can be detected by their
      ability to undergo renaturation and catalyze the phosphorylation of a peptide
      substrate that corresponds to amino acid residues 297 to 331 of the 47-kDa
      subunit of the nicotinamide-adenine dinucleotide phosphate-oxidase complex (p47
      phox) fixed within a gel. In this study, we demonstrate that N-acetylsphingosine
      (C2-ceramide) and a variety of sphingoid bases (e.g., D-erythrosphingosine) block
      activation of the 63- and 69-kDa Paks in neutrophils. The concentrations of these
      lipids that were effective in blocking Pak activation were similar to those that
      inhibit a variety of neutrophil responses. Activation of the 63- and 69-kDa Paks
      was also markedly reduced in neutrophils treated with sphingomyelinase before
      stimulation. Moreover, we report that addition of C2-ceramide or D
      erythrosphingosine to neutrophils after stimulation with FMLP markedly enhances
      the rate of Pak inactivation. These effects were not mimicked by arachidonate,
      which is a potent disorganizing agent of neutrophil membranes. These data support
      and extend the proposal that sphingoid bases may establish a set point in
      neutrophils for positive stimuli.

PMID- 9780216
TI  - Endothelial cell activation by leukocyte microparticles.
AB  - The ability of polymorphonuclear leukocytes (PMNs) to modulate endothelial cell
      (EC) activation was investigated. Adding PMNs to cultured HUVECs resulted in a
      release of IL-6 (888 +/- 71 pg/ml, a 35-fold increase over release by the two
      cell types alone) and IL-8 (45.2 +/- 14.5 ng/ml, a 6.4-fold over PMN release
      alone and a 173-fold increase over EC release alone). In contrast, the release of
      TNF-alpha, IL-1beta, and platelet-derived growth factor was not affected by the
      EC-PMN coculture. Neutralizing mAbs to ICAM-1 or beta2 integrins or a physical
      segregation of PMNs and ECs did not reduce EC stimulation. In contrast, cell-free
      supernatants of PMNs recapitulated EC activation with an 18-fold up-regulation of
      EC IL-6 mRNA. The filtration of PMN supernatant or PMN pretreatment with
      metabolic antagonists or membrane cross-linking agents all suppressed EC
      activation. By flow cytometry, PMNs released in the supernatant, heterogeneous
      membrane-derived microparticles containing discrete proteins of 28 to 250 kDa as
      resolved by SDS-PAGE. PMN microparticle formation was enhanced by inflammatory
      stimuli, including formyl peptide and phorbol ester, and was time-dependent,
      reaching a plateau after a 1-h incubation from stimulation. Purified PMN
      microparticles induced EC IL-6 release in a reaction that was quantitatively
      indistinguishable from that observed with unfractionated PMN supernatant and
      unaffected by a neutralizing Ab to soluble IL-6R. These findings demonstrate that
      membrane microparticles released from stimulated PMNs are competent inflammatory
      mediators to produce EC activation and cytokine gene induction.

PMID- 9780217
TI  - Complement-induced expression of chemokine genes in endothelium: regulation by IL
      1-dependent and -independent mechanisms.
AB  - Activation of complement in the vicinity of endothelium is thought to contribute
      to the tissue manifestations of inflammatory and immune responses. Endothelial
      cells contribute to these processes in part by the elaboration of chemokines that
      activate various leukocytes and direct their migration into tissues. We
      investigated the mechanisms by which activation of complement on endothelial cell
      surfaces might influence the expression of chemokine genes in endothelial cells.
      In a model for the immune reaction occurring in a xenograft, human serum, as a
      source of xenoreactive anti-endothelial Abs and complement, induced expression of
      the monocyte chemotactic protein-1 (MCP-1), IL-8, and RANTES genes. The MCP-1 and
      IL-8 genes were expressed within 3 h as a first phase and at > 12 h as a second
      phase. The RANTES gene was expressed in porcine endothelial cells only 12 h after
      exposure to human serum. The expression of these genes required activation of
      complement and assembly of membrane attack complex, as it was inhibited by
      soluble CR1 and did not occur in the absence of C8. The early phase of MCP-1 and
      IL-8 gene expression did not require de novo protein synthesis. The late phase of
      MCP-1, IL-8, and RANTES gene expression predominantly required the production of
      IL-1alpha as an intermediate step. The results indicate that the expression of
      chemokine genes in endothelial cells occurs as a function of differential
      responses to complement and may in part be conditioned by the availability of IL
      1alpha.

PMID- 9780218
TI  - Endothelial selectins and alpha4 integrins regulate independent pathways of T
      lymphocyte recruitment in the pulmonary immune response.
AB  - The cell adhesion molecules (CAMs) required for T lymphocyte recruitment during
      pulmonary immune responses have not been defined. Our laboratories recently
      reported that intratracheal (IT) challenge of sensitized mice with SRBC induced
      prolonged expression of vascular P-selectin, E-selectin, and VCAM-1, particularly
      in areas of mononuclear leukocyte infiltration. A surge in the number of
      circulating T lymphocytes expressing selectin ligands preceded the peak
      accumulation of T cells in the lung. In addition, a significant percentage of the
      T cells recovered from the lung expressed selectin ligands as well. The current
      study demonstrates that cultured T lymphoblasts use both selectin ligands and
      alpha4 integrins to enter the airspace and interstitium during the response to
      SRBC. Fluorescently labeled T lymphoblasts, derived via activation on CD3 and
      growth in low dose IL-2, showed inflammation-specific recruitment into lungs
      harvested 24 h after cell infusion. Their flux paralleled the accumulation of
      host lymphocytes in the lung, with both peaking 2 to 4 days after SRBC challenge.
      Trafficking studies conducted over a 24-h period during peak lymphocyte
      accumulation in the lungs revealed preferential recruitment of labeled T
      lymphoblasts expressing P- and E-selectin ligands. In addition, mAb blockade of
      the alpha4 integrins and targeted deletion of an alpha(1,3)fucosyltransferase
      essential for selectin ligand synthesis each reduced labeled T lymphoblast
      trafficking to a significant degree. Furthermore, alpha4 integrin blockade
      reduced the trafficking of the selectin ligand-deficient cells into the airspace,
      confirming that its contribution is in part independent from the vascular
      selectins. These findings imply that both selectin ligands and alpha4 integrins
      participate in T lymphoblast recruitment during the pulmonary immune response to
      IT SRBC.

PMID- 9780219
TI  - Detection of HIV-1-specific CTLs in the semen of HIV-infected individuals.
AB  - CTLs play an important role in controlling cell-associated HIV. Since the
      majority of HIV infections are acquired through sexual transmission, we
      investigated whether antiviral CTLs were present in the male urogenital tract
      using semen as a source of T cells. We were able to establish anti-HIV cytolytic
      lines in five of five HIV-infected men with CD4 counts of >500/microl, although
      cloning efficiencies were lower than with peripheral blood-derived T cells. CTLs
      generated from the semen of three men were analyzed in detail and showed a
      broadly active response, recognizing gag, env, and pol proteins. Detailed
      analysis of two gag-specific clones from one of the individuals demonstrated HLA
      class I restriction and recognition of the same p24 epitope (EQASQEVKNWMT). In
      summary, our results demonstrate the presence of a broad CTL response to HIV in
      the urogenital tract and provide a rationale for further studies of local
      enhancement of genital mucosal responses by anti-HIV immunization.

PMID- 9780220
TI  - Localization of quantitative trait loci regulating adjuvant-induced arthritis in
      rats: evidence for genetic factors common to multiple autoimmune diseases.
AB  - Adjuvant-induced arthritis (AIA) in rats is a widely used autoimmune experimental
      model with many features similar to rheumatoid arthritis (RA). To identify
      potential genetic regulatory mechanisms in RA, we conducted genome-wide linkage
      analysis in F2 progeny of arthritis-susceptible Dark Agouti (DA) and relatively
      resistant Fischer 344 (F344) inbred rats. We compared the data with our
      previously reported investigation of collagen-induced arthritis (CIA), which was
      expanded in the follow-up study reported in this work. We found two quantitative
      trait loci (QTLs) in common, i.e., Aia1/Cia1 on chromosome 20, which includes the
      MHC, and Aia3/Cia3 on chromosome 4. We also identified a second unique QTL in
      AIA, Aia2, on chromosome 4. Interestingly, the QTL region on chromosome 4
      (Aia3/Cia3), like the MHC, appears to be involved in several other autoimmune
      diseases in rats, including insulin-dependent diabetes, thyroiditis, and
      experimental autoimmune uveitis. Moreover, an analysis of conserved synteny among
      rats, mice, and humans suggested that Aia2 and Aia3/Cia3, like Aia1/Cia1, contain
      candidate genes for several autoimmune/inflammatory diseases in mice and humans,
      including diabetes, systemic lupus erythematosus, inflammatory bowel disease,
      asthma/atopy, multiple sclerosis, and RA. The rat models appear to provide a
      powerful complementary approach to identify and characterize candidate genes that
      may contribute to autoimmune diseases in several species.

PMID- 9780221
TI  - IL-10 impacts autoimmune diabetes via a CD8+ T cell pathway circumventing the
      requirement for CD4+ T and B lymphocytes.
AB  - IL-10 is essential for an early phase of diabetes in nonobese diabetic (NOD)
      mice, but later becomes protective against its development. The mechanism by
      which IL-10 mediates the pathway to diabetes in these mice is unknown. Herein, we
      dissected the cellular and costimulation requirements for diabetes in transgenic
      (tg) NOD mice that expressed IL-10 in their pancreatic islets (IL-10-NOD mice).
      We found that IL-10 alone did not cause diabetes because the offspring (IL-10-NOD
      scid mice) from back-crosses of IL-10-NOD mice with NOD-scid mice had no
      diabetes. Moreover, these IL-10-NOD-scid mice were free of lymphocytic
      infiltration. Treatment of IL-10-NOD mice with depleting anti-CD4 mAb or control
      mAb had no effect on diabetes. Surprisingly, depletion of CD8+ T cells by
      treatment with the corresponding mAb inhibited diabetes without attenuating
      insulitis, demonstrating a critical role for CD8+ T cells in the disease process.
      Interestingly, B cell-deficient IL-10-NOD mice readily developed diabetes with
      kinetics and incidence similar to those observed in wild-type mice, demonstrating
      that B lymphocytes as APCs were not required in the disease process.
      Administration of anti-CD40 ligand (CD40L) mAb did not prevent disease,
      indicating that CD40/CD40L costimulation is not required for diabetes in IL-10
      NOD mice. Immunization of IL-10-NOD mice with CFA or heat-shock protein 65, known
      to block diabetes in NOD mice, had no effect on their diabetes. We demonstrate
      that IL-10 contributes early to the pathology of diabetes via a CD8+ T cell
      pathway, eliminating the requirement for B lymphocytes and CD40-CD40L
      costimulation. Our findings provide a mechanism for the participation of IL-10 in
      the early development of diabetes.

PMID- 9780222
TI  - Selective accumulation of related CD4+ T cell clones in the synovial fluid of
      patients with rheumatoid arthritis.
AB  - The role of T cells in the pathogenesis of rheumatoid arthritis (RA), especially
      in the perpetuation of advanced disease, remains unclear. Previous studies have
      focused on the TCR repertoire of synovial T cells in an attempt to determine
      whether the pattern of expression is characteristic of Ag-stimulated populations.
      However, the results of past studies have been conflicting. In the present work,
      we have undertaken an extensive analysis of the TCRs expressed by CD4+ T cells
      freshly isolated from synovial fluid of different joints and blood in three
      patients with established RA. Despite marked heterogeneity of synovial TCR
      expression, the results showed that 20 to 30% of the TCR beta-chain gene (TCRB)
      sequences found in one joint were also expressed in a second joint, but not in
      peripheral blood T cells of the same individual. Analysis of expressed TCRB
      complementarity-determining region 3 sequences showed the presence of multiple
      expanded clonal populations that were not predicted by quantitation of beta-chain
      variable region (Vbeta) expression by immunofluorescence staining. These studies
      also demonstrated sets of related, but different, complementarity-determining
      region 3 nucleotide sequences that encoded identical or highly homologous beta
      chain amino acid sequences. Analysis of matching T cell clones derived from the
      joint by limiting dilution culture confirmed coexpression of highly homologous
      TCR alpha-chain gene (TCRA) and TCRB sequences. Together, these studies suggest
      that a significant proportion of synovial CD4+ T cells has been selected and
      expanded by conventional Ag(s) in this disease.

PMID- 9780223
TI  - Differential expression of inflammatory cytokines parallels progression of
      central nervous system pathology in two clinically distinct models of multiple
      sclerosis.
AB  - Multiple sclerosis is an immune-mediated demyelinating disease of unknown
      etiology that presents with either a chronic-progressive or relapsing-remitting
      clinical course. Theiler's murine encephalomyelitis virus-induced demyelinating
      disease (TMEV-IDD) and relapsing-remitting experimental autoimmune
      encephalomyelitis (R-EAE) in the SJL/J mouse are both relevant murine CD4+ T cell
      mediated demyelinating models that recapitulate the multiple sclerosis disease
      phenotypes. To determine the cellular and molecular basis for these observed
      differences in clinical course, we quantitatively analyzed the temporal
      expression of pro- and antiinflammatory cytokine mRNA expression in the central
      nervous system (CNS) and the phenotype of the inflammatory mononuclear
      infiltrates. TMEV-infected SJL/J mice expressed IFN-gamma, TNF-alpha, IL-10, and
      IL-4 mRNA during the preclinical phase, and their levels continued to increase
      throughout the duration of the chronic-progressive disease course. These data
      correlated with the continued presence of both CD4+ T cells and F4/80+
      macrophages within the CNS infiltrates. In contrast, SJL/J mice with PLP(139-151)
      induced R-EAE displayed a biphasic pattern of CNS expression for the
      proinflammatory cytokines, IFN-gamma and TNF-alpha, with expression peaking at
      the height of the acute phase and relapse(s). This pattern correlated with
      dynamic changes in the CD4+ T cell and F4/80+ macrophage populations during
      relapsing-remitting disease progression. Interestingly, IL-4 message was
      undetectable until disease remission(s), demonstrating its potential role in the
      intrinsic regulation of ongoing disease, whereas IL-10 was continuously
      expressed, arguing against a regulatory role in either disease. These data
      suggest that the kinetics of cytokine expression together with the nature of the
      persistent inflammatory infiltrates are major contributors to the differences in
      clinical course between TMEV-IDD and R-EAE.

PMID- 9780224
TI  - Human class I supertypes and CTL repertoires extend to chimpanzees.
AB  - Using an in vitro peptide stimulation strategy, two chimpanzees that were acutely
      infected by the hepatitis B virus (HBV) produced peripheral blood CTL responses
      to several HBV-encoded epitopes that are known to be recognized by class I
      restricted CTL in acutely infected humans. One animal responded to three HBV
      peptides that, in humans, are restricted by HLA-A2; the other animal responded to
      three peptides that are restricted by HLA-B35 and HLA-B51, members of the HLA-B7
      supertype in man. The peptides recognized by each chimp corresponded with the
      ability of its class I molecules to bind peptides containing the HLA-A2 and HLA
      B7 supermotifs. Similar, apparently class I-restricted CTL responses to some of
      these peptides were also detected in occasional HBV-uninfected chimps. These
      results demonstrate that the CTL repertoire overlaps in humans and chimps and
      that the HLA-A2 and HLA-B7 supertypes extend to the chimpanzee. Based on these
      results, the immunogenicity and efficacy of vaccines designed to induce CTL
      responses to human HLA-restricted viral epitopes may be testable in chimpanzees.

PMID- 9780225
TI  - Expression of membrane-bound transferrin-like protein p97 on the cell surface of
      chondrocytes.
AB  - A concanavalin-A-binding protein of 76 kDa was purified from the plasma membrane
      fraction of rabbit chondrocyte cultures. Amino acid sequencing of the N-terminal
      region and of tryptic peptides of the protein, in addition to sequencing of its
      cDNA revealed that this protein is highly similar to the tumour-associated
      antigen p97. Hence, it was concluded that this protein is the rabbit form of p97.
      Western blotting, Northern blotting and reverse-transcription PCR analyses
      indicated that rabbit p97 is expressed at high levels in cartilage and
      chondrocytes, but is barely detectable in the bone, liver, kidney, small
      intestine, eye, pancreas, heart, testis, skeletal muscle, spleen and fibroblasts.
      Immunocytochemical and immunohistochemical analyses demonstrated that p97 is
      expressed in the plasma membrane of chondrocytes. p97 transcript was detected in
      all zones of the cartilage but the level was relatively low in the hypertrophic
      zone. These findings suggest that p97 is involved in maintaining the cell surface
      characteristics of chondrocytes.

PMID- 9780226
TI  - Functional characterization of the human thiopurine S-methyltransferase (TPMT)
      gene promoter.
AB  - Thiopurine S-methyltransferase (TPMT) is a cytosolic enzyme that catalyzes S
      methylation of aromatic and heterocyclic sulfhydryl compounds, including
      anticancer and immunosuppressive thiopurines. We recently isolated the human TPMT
      promoter, which does not contain TATA box or CCAAT element consensus sequences,
      but is GC rich with multiple GC boxes and other putative cis-regulatory elements.
      Here, we report the functional characterization of the TPMT promoter, revealing
      several positive regulatory elements and identifying stimulating protein 1 (Sp1)
      as an important trans-activator essential for constitutive activity in cell
      culture. One major and two closely located minor transcription start points were
      identified in HepG2 cells. Deletion analysis revealed positive cis-regulatory
      elements located in the regions -85 to -75, -68 to -58, -58 to -51 and +34 to +60
      relative to the transcription start site. DNaseI footprinting analysis and
      cotransfection in Drosophila Schneider SL2 cells documented that Sp1 binds to the
      TPMT promoter and is important for constitutive activity. We conclude that
      constitutive transcription of the TPMT gene involves a limited upstream GC-rich
      DNA sequence, containing multiple GC boxes, and that transcription factor Sp1 [or
      related protein(s)] is an important trans-activator of this TATA-less promoter.

PMID- 9780227
TI  - Butylated hydroxytoluene modulates DNA methylation in rats.
AB  - The major observation of this investigation is that a single intraperitoneal
      injection of butylated hydroxytoluene (BHT, 60 mg/kg body mass) results within a
      few hours in a strong increase in nuclear DNA(cytosine-5)-methyl transferase
      (methyl transferase) activity in the liver, kidneys, heart, spleen, brain and
      lungs of male rats. In most organs, the rise in methyl transferase activity is
      observed as early as 4 h after BHT injection, it reaches a maximum at 8 h and
      then, except for lungs and brain, gradually decreases to its initial level at 16
      h. At the maximum induction times, the methyl transferase activity in liver,
      kidney and spleen increases by about 16-, 3- and 5-fold, respectively. A second
      BHT injection at 96 h results in a secondary rise in hepatic methyl transferase
      activity. Isoelectric focusing electrophoresis of control rat liver nuclear
      extracts showed methyl transferase activity in the pI 4.7 and 7.4 protein
      fractions. Both fractions methylate calf thymus DNA better than they do
      Drosophila melanogaster DNA. In similar extracts from BHT-treated rats, the
      methyl transferase activity is found in three protein fractions with pI values
      equal to 4.0, 6.2 and 9.5, respectively. Most of the methyl transferase fractions
      from the livers of BHT-treated rats methylate the completely unmethylated D.
      melanogaster DNA better than they do calf thymus DNA. Thus, BHT induces methyl
      transferase activity that preferably provides de novo DNA methylation. BHT
      injection had no significant effect on the hepatic contents of S
      adenosylmethionine (AdoMet), S-adenosylhomocysteine (AdoHcy) and AdoMet/AdoHcy
      ratios. While BHT injection did not alter the 5-methyldeoxycytidine content in
      liver DNA, it did appear to alter such content in other organs. BHT appears to
      cause the reversible changes in the methylation status of an internal cytosine
      residue in some CCGG sites of the rat liver cytosine DNA-methyl transferase gene.
      BHT induces also hypomethylation of the renal methyl transferase gene and the
      hepatic c-Ha-ras gene. While BHT also increases the hepatic mRNA transcripts for
      the S-adenosylmethionine synthetase and the p53 genes, it had no detectable
      effects on the corresponding mRNA transcripts for methyl transferase homologous
      to murine methyl transferase. Thus, BHT induces tissue-specific reversible
      changes in methyl transferase activity and methylation of total DNA and various
      genes in rats. A strong increase in methyl transferase activity in rat liver is
      accompanied with BHT-induced change in the methyl transferase set observed in
      this organ.

PMID- 9780228
TI  - The biosynthetic gene cluster for the macrolactone ring of the immunosuppressant
      FK506.
AB  - Biosynthesis of the macrolactone ring of FK506 involves 10 elongation cycles that
      mechanistically resemble the steps in fatty acid synthesis. Sequencing of a 40-kb
      DNA segment of the FK506 gene cluster from Streptomyces sp. MA6548 has revealed
      two additional polyketide synthases (PKS) genes fkbB and fkbC which lie upstream
      of fkbA, a PKS gene recently shown to be responsible for the last four
      condensation steps of the FK506 biosynthesis [Motamedi, H., Cai, S. J., Shafiee,
      A. & Elliston, K. O. (1997) Eur. J. Biochem. 244, 74-80]. fkbB and fkbC are
      contiguous and encode respectively, the first (790129 Da) and the second (374438
      Da) components of the FK506 polyketide synthase, a complex of three multidomain
      polypeptides. The predicted domain structures of FkbB and FkbC are analogous to
      that of FkbA and comprise 30 fatty-acid-synthase(FAS)-like domains arranged in 6
      modules. Each module performs a specific extension cycle in the assembly of the
      carbon skeleton of the FK506 macrolactone ring. The component activities for the
      initiation of the polyketide chain consisting of a dihydrocyclohexenylcarbonyl
      coenzyme A (CoA) synthetase and a dihydrocyclohexenylcarbonyl CoA reductase
      required for the formation of the dihydrocyclohexylcarbonyl CoA starter unit and
      an acyl-carrier-protein to which the starter unit is anchored and translocated to
      the appropriate site on the PKS multienzyme are located at the N-terminal region
      of the FkbB polypeptide. A third gene, fkbL, lies at one end of the cluster and
      encodes lysine cyclodeaminase which catalyzes alpha-deamination and cyclization
      of the lysine into pipecolate. A fourth gene fkbP located at the other end of the
      sequence reported here encodes a peptide synthetase required for the activation
      and incorporation of the pipecolate moiety into the completed acyl chain. Finally
      the cluster carries a gene, fkbO, whose product is presumed to carry out a post
      polyketide oxidation step of the FK506 marocycle.

PMID- 9780229
TI  - Phosphorylation-specific antibodies for human cardiac troponin-I.
AB  - A panel of seven monoclonal antibodies (mAbs) raised against cardiac troponin-I
      (CdTnI) isolated from canine and human hearts, which have been shown to be
      cardiac-specific but cross-species reactive [Cummins, B., Aukland, M. L. &
      Cummins, P. (1987) Amer. Heart J. 113, 1333-1344], were used in this study. These
      mAbs were tested against recombinant wild-type and mutant human CdTnI proteins to
      assess their value as probes for the phosphorylation status of CdTnI. Four mAbs
      were found to react positively with the recombinant wild-type protein and their
      epitopes were contained in residues 31-210 of the human cardiac protein. Two of
      these mAbs appeared to be directed against the same epitope site within this
      region. The remaining three mAbs only reacted against the recombinant wild-type
      protein when it was phosphorylated, showing that these three antibodies were
      directed against the phosphate group(s) on Ser23 and/or Ser24. In order to
      investigate this further, a series of single and double mutants of CdTnI were
      used in which either Ala (to direct the enzymatic phosphorylation) or Asp (to
      mimic the phosphate group) replaced the Ser23 and/or Ser24. It was found the all
      three mAbs were able to react with the mono-phosphorylated form of the
      [Ala23]CdTnI single mutant but not the mono-phosphorylated form of the
      [Ala24]CdTnI single mutant, showing that they specifically required
      phosphorylation at Ser24. Experiments with a synthetic peptide composed of
      residues 1-29 of human CdTnI confirmed these data. Two of the three
      phosphorylation-specific mAbs were able to react with mutants containing either
      two Asp residues replacing Ser23 and Ser24 or one Asp residue instead of Ser24,
      indicating that a negative charge at position Ser24 is sufficient to invoke a
      reaction. The other mAb was more specific in that it would only react with CdTnI
      species with a phosphate group on Ser24.

PMID- 9780230
TI  - Phorbol ester causes ligand-independent activation of the androgen receptor.
AB  - We have examined the human androgen receptor (hAR) for its ability to activate AR
      dependent transcription of a transgene in a ligand-independent manner. The
      transcriptional activity was determined by analysis of chloramphenicol
      acetyltransferase (CAT) activity in T47D cells cotransfected with a plasmid
      expressing the hAR and a natural AR-regulated promoter (the MVDP androgen
      dependent enhancer) ligated to the reporter CAT gene. In this study, the effects
      of the protein kinase C (PKC) activator 12-O-tetradecanoyphorbol-13 acetate (TPA)
      on AR activity were tested. We demonstrated that in the absence of androgen, TPA
      enhanced AR-mediated transactivation by 10-12-fold. This effect was specific of
      the PKC pathway since stimulation to the PKA pathway did not activate the
      unliganded AR. This ligand-independent pathway can function through another
      androgen-regulated promoter as shown by the use of the mouse mammary tumor virus
      MMTV-CAT reporter. The human glucocorticoid receptor (hGR) and the rabbit
      progesterone receptor (rPR) could not be activated by TPA, indicating that the
      effects are not universal for steroid receptors. A reporter plasmid containing
      the MVDP androgen response element (ARE) in front of the thymidine kinase
      promoter ligated to the CAT gene was activated by DHT but not by TPA, indicating
      that the context of the natural promoter is critical for ligand-independent
      activation of the AR. Exogenous c-jun enhanced transcriptional activation by the
      AR in a ligand-dependent manner, but had no effect in the absence of DHT. Base
      pair substitutions in both AR-binding (5'-TGTTCT-3' to 5'-TTTTTT-3') and NF1
      binding (5'-GTGGCTG-3' to 5'-GTTTTTG-3') sites resulted in a loss of TPA
      responsiveness. Our results suggest that ligand-independent activation of the AR
      by TPA results from interaction of unliganded AR with other proteins in the
      transcription machinery.

PMID- 9780231
TI  - DNase I hypersensitive sites in the 5' flanking region of the human plasminogen
      activator inhibitor type 2 (PAI-2) gene are associated with basal and tumor
      necrosis factor-alpha-induced transcription in monocytes.
AB  - The plasminogen activator inhibitor type 2 (PAI-2) gene encodes a serine
      proteinase inhibitor (serpin) which is rapidly induced in response to the
      inflammatory cytokine, tumour necrosis factor-alpha (TNFalpha) in monocytes and
      macrophages. As an initial step towards understanding the molecular mechanisms
      underlying PAI-2 gene regulation in monocytes, we report here the analysis of the
      chromatin structure of 9.6 kb of 5' flanking region of the human PAI-2 gene for
      potential cis-acting regulatory regions using DNase I hypersensitivity mapping.
      Sites sensitive to DNase I were mapped in two monocytic cell lines representative
      of early monocytic differentiation; U937 cells, which synthesise low constitutive
      levels of PAI-2 that were induced following treatment with TNFalpha, and a
      MonoMac6 cell line which did not synthesise PAI-2 even after treatment with
      TNFalpha. Six DNase I hypersensitive sites (DHS) were identified; three upstream
      of the transcription initiation site (DH1, DH2, DH3) and three downstream of the
      transcription initiation site which were contained within intron A (DH4, DH5) and
      the exon 2/intron B junction (DH6). Among these, one distally located DH site
      (DH2) disappeared in both cell lines following treatment with TNFalpha. Two DH
      sites (DH1, DH6) were absent in PAI-2-producing U937 cells, but were present in
      MonoMac6 cells, which did not produce PAI-2, indicating the possible involvement
      of negative regulatory elements in the suppression of PAI-2 gene expression. The
      results demonstrate the involvement of chromatin structure in transcriptional
      responsiveness of the PAI-2 gene promoter and identify several loci which may be
      key control regions for PAI-2 gene transcription.

PMID- 9780232
TI  - The influence of the central region containing residues 19-25 on the aggregation
      properties and secondary structure of Alzheimer's beta-amyloid peptide.
AB  - Alzheimer's beta-amyloid peptide (Abeta) is a 39- to 43-amino-acid peptide that
      is the major component of neuritic plaques found in Alzheimer's disease (AD). The
      central region of Abeta plays a crucial role in many of its properties, including
      aggregation, neurotoxicity, proteolytic processing and interactions with other
      proteins, such as apolipoprotein E. Two mutations in this region, Ala21-->Gly and
      Glu22-->Gln, give rise to early onset forms of disease. We have studied several
      peptides based on the central region of Abeta in order to clarify the influence
      of specific amino acid residues on physicochemical behaviour. To avoid
      difficulties due to oxidation of Met35, the latter was replaced by the amino acid
      isostere, norleucine (Ahx), giving [Ahx35]Abeta-(25-35)-amide as a prototype
      structure. To this prototype, addition of pairs of amino acid residues from the
      sequence of Abeta, forming the corresponding 23-, 21- and 19-35 derivatives,
      resulted in peptides that aggregated to form fibrils of diameter 6-10 nm. The
      rate of aggregation was more rapid as peptide length increased. Circular
      dichroism spectra of aged solutions of peptides revealed that aggregation was
      accompanied by a transition from random structure to beta sheet for some, but not
      all, peptides. The mutation from Ala to Gly at position 21 increased the rate of
      aggregation and altered the tendency to adopt secondary structure in the
      direction away from alpha helix and towards beta sheet. In individuals with the
      Ala21-->Gly mutation, these results would suggest that truncated species with N
      termini in the region containing residues 17-20 would be more amyloidogenic than
      the wild type homologues.

PMID- 9780233
TI  - Contribution of the hydrophobicity gradient of an amphipathic peptide to its mode
      of association with lipids.
AB  - A class of peptides that associate with lipids, known as oblique-orientated
      peptides, was recently described [Brasseur R., Pillot, T., Lins, L.,
      Vandekerckhove, J. & Rosseneu, M. (1997) Trends Biochem. Sci. 22, 167-171]. Due
      to an asymmetric distribution of hydrophobic residues along the axis of the alpha
      helix, such peptides adopt an oblique orientation which can destabilise membranes
      or lipid cores. Variants of these oblique peptides, designed to have an
      homogeneous distribution of hydrophobic and hydrophilic residues along the
      helical axis, are classified as regular amphipathic peptides. These peptides are
      expected to lie parallel to the polar/apolar interface with their hydrophobic
      residues directed towards the apolar and their hydrophilic residues towards the
      polar phase. An hydrophobic, oblique-orientated peptide was identified at
      residues 56-68 in the sequence of the lecithin-cholesterol acyltransferase
      (LCAT), enzyme. This peptide is predicted to penetrate a lipid bilayer at an
      angle of 40 degrees through its more hydrophobic C-terminal end and thereby
      induce the destabilisation of a membrane or a lipid core. The LCAT-(56-68) wild
      type peptide was synthesised together with the LCAT-(56-68, 0 degrees) variant,
      in which the hydrophobicity gradient was abolished through residue permutations.
      In two other variants, designed to keep their oblique orientation, the W61
      residue was shifted either towards the more hydrophilic N-terminal at residue 57,
      or to position 68 at the hydrophobic C-terminal end of the peptide. Peptide
      induced vesicle fusion was demonstrated by fluorescence measurements using pyrene
      labeled vesicles and by monitoring of vesicle size by gel filtration. The
      interaction between peptides and lipids was monitored by measurement of the
      intrinsic tryptophan fluorescence emission of the peptides. Fluorescence
      polarisation measurements, using diphenyl hexatriene, were carried out to follow
      changes in the lipid fluidity. The LCAT-(56-68) wild-type peptide and the two
      oblique variants, induced fusion of unilamellar dimyristoylglycerophosphocholine
      vesicles. Tryptophan fluorescence emission measurements showed a 12-14 nm blue
      shift upon addition of the wild-type peptide and of the W61-->68 variant to
      lipids, whereas the fluorescence of the W61-->57 variant did not change
      significantly. This observation supports the insertion of the more hydrophobic C
      terminal residues into the lipid phase, as predicted by the theoretical
      calculations. In contrast, the 0 degrees variant peptide had no fusogenic
      activity, and it associated with lipids to form small discoidal lipid/peptide
      complexes. The phospholipid transition temperature was decreased after addition
      of the wild-type, the W61-->68 and W61-->57 fusogenic peptides, whereas the
      opposite effect was observed with the 0 degrees variant. The behaviour of the
      wild-type and variant LCAT-(56-68) peptides stresses the contribution of the
      hydrophobicity gradient along the axis of an amphipathic peptide to the mode of
      association of this peptide with lipids. This parameter consequently influences
      the structural modifications occurring to lipids upon association with
      amphipathic peptides.

PMID- 9780234
TI  - Uracil DNA glycosylase from Mycobacterium smegmatis and its distinct biochemical
      properties.
AB  - Deamination of cytosine residues contributes to the appearance of uracil in DNA.
      Uracil DNA glycosylase (UDG) initiates uracil excision repair to safeguard the
      genomic integrity. To study the mechanism of uracil excision in mycobacteria
      (organisms with G+C rich genomes), we have purified UDG from Mycobacterium
      smegmatis by more than 3000-fold. The molecular mass of M. smegmatis UDG, as
      determined by SDS/PAGE, is approximately 25 kDa and it shows maximum activity at
      pH 8.0. The N-terminal sequence analysis shows that the initiating amino acid,
      formyl-methionine is cleaved from the mature protein. More interestingly, unlike
      Escherichia coli UDG, which forms a physiologically irreversible complex with the
      inhibitor protein Ugi, M. smegmatis UDG forms a dissociable complex with it. M.
      smegmatis UDG excises uracil from the 5'-terminal position of the 5'
      phosphorylated substrates. However, its excision from the 3'-penultimate position
      is extremely poor. Similar to E. coli UDG, M. smegmatis UDG also uses pd(UN)p as
      its minimal substrate. However, in contrast to E. coli UDG, which excises uracil
      from different loop positions of tetraloop hairpin substrates with highly
      variable efficiencies, M. smegmatis UDG excises the same uracil residues with
      comparable efficiencies. Kinetic parameters (Km and Vmax) for uracil release from
      synthetic substrates suggest that M. smegmatis UDG is an efficient enzyme and
      better suited for molecular biology applications. We discuss the usefulness of
      the distinct biochemical properties of M. smegmatis UDG in the possible design of
      selective inhibitors against it.

PMID- 9780235
TI  - Membrane-bound proton-translocating pyrophosphatase of Syntrophus gentianae, a
      syntrophically benzoate-degrading fermenting bacterium.
AB  - Syntrophus gentianae is a strictly anaerobic bacterium which ferments benzoate to
      acetate, CO2 and H2 in the presence of hydrogen-utilizing partner bacteria.
      Benzoate is activated by a benzoyl CoA ligase enzyme which forms AMP and
      pyrophosphate as coproducts. Pyrophosphatase activity was found to be largely
      membrane bound. Pyrophosphate hydrolysis was associated with proton translocation
      across the cytoplasmic membrane. Proton translocation could be abolished by the
      protonophor carbonylcyanide p-chlorophenylhydrazone, and could also be coupled to
      ATP formation in membrane vesicle preparations. The ratio of ATP
      formation/pyrophosphate hydrolysis was 1:3. The reverse reaction, ATP-dependent
      pyrophosphate synthesis, was possible with the same coupling stoichiometry.
      Pyrophosphatase was 90% saturated at 1 mM pyrophosphate; pyrophosphate
      concentrations higher than 5 mM inhibited enzyme activity. Inhibition studies
      with ATP and EDTA indicated that MgPPi- was probably the physiological substrate.
      The optimum temperature was 35 degrees C. In the presence of Mg2+, the enzyme was
      remarkably heat stable, with 50% of its maximum activity after 10 min at 60
      degrees C. Exogenously added pyrophosphate could not be used for energy
      conservation.

PMID- 9780236
TI  - Association of His117 in the D2 protein of photosystem II with a chlorophyll that
      affects excitation-energy transfer efficiency to the reaction center.
AB  - His117 of the D2 protein of photosystem II (PS II) is a conserved residue in the
      second transmembrane region of the protein and has been suggested to bind
      chlorophyll. Nine site-directed mutations were introduced at residue 117, using
      both photosystem I (PS I)-containing and PS I-less background strains of the
      cyanobacterium Synechocystis sp. PCC 6803. Of these nine, four (H117C, H117M,
      H117N, and H117T) were photoautotrophic in the PS I-containing background. The
      other mutants (H117F, H117L, H117P, H117R, and H117Y) did not accumulate
      appreciable amounts of PS II in their thylakoids. The type of residues that can
      functionally replace His117 support the notion of His117 serving as a chlorophyll
      ligand. The properties of the H117N and H117T mutants were characterized in more
      detail. Whereas the properties of the H117N mutant were close to those of wild
      type, in the H117T mutant the 77-K fluorescence emission spectrum shows a much
      smaller amplitude at 695 nm than expected on the basis of the amount of PS II
      that is present. Moreover, in H117T, the amount of light needed to half-saturate
      O2-evolution rates was twofold higher than in the control strain, and the
      variable fluorescence yield was quenched. However, O2 evolution rates at
      saturating light intensity and electron-transport kinetics were normal in the
      mutant. Also, the radical accessory chlorophyll (Chlz+) formed by donation of an
      electron to the PS-II reaction center could be generated normally by illumination
      at low temperature in the H117T mutant. We conclude that the chlorophyll
      associated with residue 117 of the D2 protein is important for efficient
      excitation transfer between the proximal antenna and the PS II reaction center. A
      possible mechanism involving a chlorophyll cation to explain the quenching in the
      H117T mutant is discussed.

PMID- 9780237
TI  - Self-reported use of mammography and insurance status among women aged > or =40
      years--United States, 1991-1992 and 1996-1997.
AB  - In the United States, breast cancer is the most commonly diagnosed malignancy
      among women and the second leading cause of cancer death. Lack of health
      insurance coverage often is an important financial barrier to seeking preventive
      health care such as mammography screenings. To assess mammography use and the
      impact of insurance status on mammography use, state-specific proportions of
      women aged > or =40 years who reported receiving a mammogram during the preceding
      2 years by insurance status were derived using data from the Behavioral Risk
      Factor Surveillance System (BRFSS) for 1991-1992 and 1996-1997. This report
      describes the results of this analysis, which indicate that the percentage of
      women reporting having had a screening mammogram during the previous 2 years
      increased, but women with insurance were substantially more likely than women
      without insurance to have had a mammogram.

PMID- 9780238
TI  - Update: influenza activity--worldwide, April-September 1998.
AB  - In collaboration with the World Health Organization (WHO), the WHO international
      network of approximately 110 collaborating laboratories in 83 countries, and U.S.
      state and local health departments, CDC conducts surveillance to monitor
      influenza activity and to detect antigenic changes in the circulating strains of
      influenza viruses. During October 1997-April 1998. influenza activity was
      moderate to severe in the Northern Hemisphere. Influenza A(H3N2) viruses were
      predominant, but influenza A(H1N1) viruses were associated with outbreaks, and
      influenza B viruses were identified sporadically in all regions. Since April
      1998, increased influenza outbreak and epidemic level activity, primarily
      associated with influenza A(H3N2), has been reported in the Southern Hemisphere.
      This report summarizes worldwide influenza activity during April-September 1998
      and the antigenic characteristics of influenza isolates collected during April
      September.

PMID- 9780239
TI  - Outbreaks of group B meningococcal disease--Florida, 1995 and 1997.
AB  - Since 1992, Neisseria meningitidis serogroup B strains have caused several
      community- and school-based outbreaks in the United States. Response to such
      outbreaks is difficult because no serogroup B vaccine is licensed currently for
      use in the United States, and mass chemoprophylaxis has been evaluated only in
      restricted settings. This report describes the use of mass prophylaxis to control
      outbreaks of serogroup B meningococcal disease in Florida in two unusual
      settings: a hotel resort and a nursing home.

PMID- 9780240
TI  - Incidence of initiation of cigarette smoking--United States, 1965-1996.
AB  - Tobacco use is the single leading preventable cause of death in the United
      States, and the risk for smoking-attributable disease increases the earlier in
      life smoking begins. Trends in the initiation of cigarette smoking are important
      indicators for directing and evaluating prevention activities. CDC and the
      Substance Abuse and Mental Health Services Administration (SAMHSA) analyzed self
      reported data from the National Household Survey on Drug Abuse (NHSDA) for 1994
      1997 to study the incidence of initiation of first cigarette smoking and of first
      daily smoking in the United States during 1965-1996 among persons aged < or =66
      years and to estimate the number of new smokers aged <18 years. The findings from
      the analysis indicated that, during 1988-1996 among persons aged 12-17 years, the
      incidence of initiation of first use increased by 30% and of first daily use
      increased by 50%, and 1,226,000 persons aged <18 years became daily smokers in
      1996.

PMID- 9780242
TI  - Monitoring of human cytomegalovirus infections in pediatric bone marrow
      transplant recipients by nucleic acid sequence-based amplification.
AB  - In the diagnosis of human cytomegalovirus (HCMV) infection, it is very important
      to distinguish symptomatic from asymptomatic infection. The nucleic acid sequence
      based amplification (NASBA) technique was compared with single and nested
      polymerase chainreaction (PCR) methods. For NASBA detection, the beta2.7
      transcript was chosen as a target because of its abundant active HCMV-specific
      expression. Of 20 pediatric bone marrow transplant (BMT) recipients, 8 developed
      HCMV-related clinical symptoms. The clinical sensitivities and specificities were
      50% and 100% for single PCR, 100% and 67% for nested PCR, and 100% and 83% for
      NASBA, respectively. Follow-up of HCMV infections in pediatric BMT recipients
      showed that NASBA could both detect viral transcript prior to the onset of
      clinical symptoms and reflect clinical improvement due to antiviral therapy.
      These data suggest that NASBA should be useful for both predicting HCMV disease
      development and monitoring the effect of antiviral therapy.

PMID- 9780241
TI  - Kinetics of the antibody response against human cytomegalovirus-specific proteins
      in allogeneic bone marrow transplant recipients.
AB  - The humoral immune response against human cytomegalovirus (CMV) was
      retrospectively investigated in >800 serum samples from 31 recipients of
      allogeneic bone marrow transplants. To this end, an ELISA was performed that
      allowed the individual analysis of IgG antibodies against known antigenic domains
      of CMV-derived phospho- and glycoproteins and nonstructural polypeptides. Twenty
      nine patients developed active CMV infection after transplantation, as determined
      by repeatedly positive samples in polymerase chain reaction (PCR) assays.
      Seventeen patients responded serologically to viral replication by producing CMV
      specific antibodies against a variety of antigens. The response was detectable
      concomitantly with PCR positivity and was seen as early as 20 days after
      transplantation. High titers of glycoprotein-specific neutralizing antibodies
      were correlated with the absence of viral DNA in blood (P<.002). Nineteen
      patients developed CMV disease. Survival was associated with the production of
      high titers of CMV glycoprotein-specific antibodies in response to viral
      replication.

PMID- 9780245
TI  - Human torovirus: a new nosocomial gastrointestinal pathogen.
AB  - Studies were undertaken to determine if human torovirus is associated with
      gastroenteritis and to examine the clinical features of torovirus illness in
      children. The fecal excretion of torovirus in patients with gastroenteritis was
      compared with that in matched asymptomatic controls in a case-control study.
      Toroviruses were identified in 72 (35.0%) of 206 gastroenteritis cases compared
      with 30 (14.5%) of 206 controls (P<.001). Clinical features of torovirus
      gastroenteritis in 172 patients positive for torovirus were compared with those
      of 115 patients infected with rotavirus or astrovirus. Persons infected with
      torovirus were more frequently immunocompromised (43.0% vs. 15.7%) and
      nosocomially infected (57.6% vs. 31.3%). They also experienced less vomiting
      (46.4% vs. 66.7%) but had more bloody diarrhea (11.2% vs. 1.8%). An antibody
      response to torovirus developed mainly in older, nonimmunocompromised children
      (P<.01). These studies demonstrate an association between torovirus excretion and
      gastroenteritis in the pediatric population among immunocompromised hospitalized
      patients and in previously healthy patients.

PMID- 9780243
TI  - Early diagnosis of primary human herpesvirus 6 infection in childhood: serology,
      polymerase chain reaction, and virus load.
AB  - Qualitative and quantitative polymerase chain reaction (PCR) for human
      herpesvirus 6 (HHV-6) DNA in whole blood and plasma was correlated with serology
      and clinical assessment in 143 children hospitalized for undifferentiated febrile
      illness to evaluate options for diagnosis of primary HHV-6 infection on the acute
      blood specimen. PCR and serology for HHV-7 were done in parallel to define
      serologic cross-reactions. Using HHV-6 seroconversion as the reference standard,
      detection of HHV-6 DNA in whole blood in the absence of antibody in the plasma
      was the most reliable evidence of primary HHV-6 infection. Detection of HHV-6 DNA
      in plasma and a high virus load in whole blood (>3.3 log10 copies/5 microL) had a
      sensitivity of 90% and 100%, respectively, in diagnosing primary HHV-6 infection.
      However, both were occasionally found in patients with other infections, possibly
      associated with HHV-6 reactivation. Maternal antibody may confound interpretation
      of serology in patients under 3 months of age.

PMID- 9780244
TI  - Evidence for zanamivir resistance in an immunocompromised child infected with
      influenza B virus.
AB  - Zanamivir, a neuraminidase inhibitor, has shown promise as a drug to control
      influenza. During prolonged treatment with zanamivir, a mutant virus was isolated
      from an immunocompromised child infected with influenza B virus. A hemagglutinin
      mutation (198 Thr-->Ile) reduced the virus affinity for receptors found on
      susceptible human cells. A mutation in the neuraminidase active site (152 Arg-
      >Lys) led to a 1000-fold reduction in the enzyme sensitivity to zanamivir. When
      tested in ferrets, the mutant virus had less virulence than the parent; however,
      it had a growth preference over the parent in zanamivir-treated animals. Despite
      these changes, the sensitivity of the mutant virus to zanamivir assessed by a
      standard test in MDCK cells was unaffected. These data indicate that the current
      methods for monitoring resistant mutants are potentially flawed because no tissue
      culture system adequately reflects the receptor specificity of human respiratory
      tract epithelium.

PMID- 9780246
TI  - Differing infection patterns of dengue and yellow fever viruses in a human
      hepatoma cell line.
AB  - Dengue (DEN) and yellow fever (YF) viruses are responsible for human diseases
      with symptoms ranging from mild fever to hepatitis and/or hemorrhages. Whereas
      DEN virus typically induces only limited foci of necrosis in the liver, YF virus
      infection is characterized by devastating lesions. In a human hepatoma cell line
      (HepG2), the kinetics of DEN and YF virus replication and release from the cells
      and the nature of host cell response to viral infection were compared. DEN virus
      infection was characterized by the early appearance of intracellular viral
      antigens, major ultrastructural cytopathic changes as early as 32 h after
      infection, extensive apoptotic cell death, and a low production of infectious
      particles. In contrast, YF virus grew exponentially to high titers and induced
      cytopathic changes only 72 h after infection. Differences between the infection
      processes of the two viruses observed in the hepatoma cell line may explain the
      different liver pathologies.

PMID- 9780247
TI  - Activation and cell cycle antigens in CD4+ and CD8+ T cells correlate with plasma
      human immunodeficiency virus (HIV-1) RNA level in HIV-1 infection.
AB  - The relationship between T cell activation and human immunodeficiency virus type
      1 (HIV-1) replication was studied in HIV-infected subjects, 20 with and 10
      without anti-HIV treatment. Expression of Ki-67 proliferation-associated antigen
      was increased in CD4+ and CD8+ T cells and correlated with HLA-DR. In subjects
      without anti-HIV treatment, the plasma HIV-1 RNA level correlated with HLA-DR in
      CD4+ T cells, with Ki-67 in CD8+ T cells, and with expression of CD38 in both T
      cell subsets. A proportion of treated subjects had increased T cell activation
      despite 4 months of highly active antiretroviral treatment (HAART). In subjects
      receiving HAART, a high percentage of HLA-DR+ CD4+ T cells was associated with
      signs of opportunistic infections. This work supports the concept that, in the
      natural course of HIV-1 infection, HIV replication itself leads to general T cell
      activation and that opportunistic infections generate additional CD4+ T cell
      activation and HIV replication.

PMID- 9780248
TI  - All-trans retinoic acid inhibition of anti-CD3-induced T cell apoptosis in human
      immunodeficiency virus infection mostly concerns CD4 T lymphocytes and is
      mediated via regulation of CD95 ligand expression.
AB  - This study analyzes the influence of all-trans retinoid acid (tRA) on apoptosis
      of peripheral lymphocytes from human immunodeficiency virus (HIV)-positive
      patients. tRA inhibits the ex vivo apoptosis in T cells; a more potent effect was
      observed on activation-induced apoptosis. Phenotypic characterization of T cell
      subsets prevented from anti-CD3-induced apoptosis by tRA revealed a more potent
      effect on CD4 T cells. A central regulatory system for apoptosis is the CD95
      system, and inappropriate induction of this pathway is thought to contribute to
      AIDS pathogenesis. In investigation of CD95-based apoptosis, tRA had no effect on
      activation-dependent induction of CD95 on T lymphocytes, but it inhibited the
      induction of CD95 ligand expression on anti-CD3-activated T cells. The previously
      reported in vivo effect of tRA inhibiting HIV-associated apoptosis and the
      present observations suggest that tRA could be considered to down-regulate
      apoptosis associated with AIDS pathogenesis.

PMID- 9780249
TI  - Highly active antiretroviral therapy normalizes the function of progenitor cells
      in human immunodeficiency virus-infected patients.
AB  - CD34 cells from human immunodeficiency virus (HIV)-infected persons have been
      described to be impaired in function. The effect of highly active antiretroviral
      treatment (HAART) on the function of CD34 cells in HIV-infected patients was
      examined. Numbers and function of CD34 cells from 11 HIV-infected patients were
      determined prior to HAART and after 2, 4, 8, and 12 weeks of therapy. The mean
      number of colony-forming units (cells) per milliliter (cfu/mL) was 15.0 prior to
      HAART vs. 109.8 in healthy controls (P<.001). During HAART, the number of cfu/mL
      increased to 100.3 (P<.001). This increase in cfu/mL eliminated the differences
      between HIV-infected patients and controls. Significant increases in numbers of
      CD34 cells were not detected. Of importance, the cloning efficiency of CD34 cells
      increased from 1.7% prior to therapy to a peak at 18.7% (P=.003). In conclusion,
      HAART normalized CD34 cell function in HIV-infected patients and thus might allow
      de novo production of T lymphocytes from progenitor cells.

PMID- 9780250
TI  - Correlation between humoral responses to human immunodeficiency virus type 1
      envelope and disease progression in early-stage infection.
AB  - Human immunodeficiency virus (HIV)-1-infected rapid and slow progressors showed
      differential humoral responses against HIV envelope peptides and proteins early
      in infection. Sera from slow progressors reacted more strongly with short
      envelope peptides modeling gp160NL4-3, predominantly in gp41. Reactivity to six
      peptides (in constant regions C3, C4, and C5 of gp120 and in gp41) correlated
      with slower progression. In a novel association, reactivity to three peptides (in
      constant regions C1 and C3 and variable region V3 of gp120) correlated with
      faster progression. Envelope peptide reactivity correlated with subsequent course
      of disease progression as strongly as did reactivity to gag p24. Patients
      heterozygous for 32-bp deletions in the CCR5 coreceptor reacted more frequently
      to an epitope in gp41. Rapid progressors had greater gp120 native-to-denatured
      binding ratios than did slow progressors. While antibody-dependent cellular
      cytotoxicity against gp120 did not strongly differentiate the groups, slow
      progressors showed a broader neutralization pattern against 5 primary virus
      isolates.

PMID- 9780251
TI  - Longitudinal and cross-sectional analysis of cytotoxic T lymphocyte responses and
      their relationship to vertical human immunodeficiency virus transmission. ARIEL
      Project Investigators.
AB  - The ARIEL Project for the Prevention of HIV Transmission from Mother to Infant
      was established to evaluate virologic and immunologic parameters during vertical
      transmission. To determine the strength and breadth of the cytotoxic T lymphocyte
      (CTL) response and its correlation with human immunodeficiency virus (HIV)
      transmission, a cross-sectional study was done of 31 HIV-infected pregnant women,
      of whom 15 transmitted and 16 did not transmit HIV to their infants. The
      precursor frequencies of CTL specific for HIV-1 gag, pol, nef, and env from 5
      different isolates of the clade B of HIV-1 were determined by limiting dilution
      analysis. Results showed that variable levels of HIV-specific CTL response were
      present in HIV-infected pregnant women during and after pregnancy. In addition,
      CTL precursor frequencies specific for pol and nef were higher during pregnancy
      in nontransmitters than in transmitters. Thus, CTL responding to different HIV
      antigens may not be contributing equally to the prevention of vertical
      transmission.

PMID- 9780252
TI  - Pharmacokinetics and antiretroviral activity of lamivudine alone or when
      coadministered with zidovudine in human immunodeficiency virus type 1-infected
      pregnant women and their offspring.
AB  - The safety, pharmacokinetics, and antiretroviral activity of lamivudine alone and
      in combination with zidovudine was studied in pregnant women infected with human
      immunodeficiency virus type 1 (HIV-1) and their neonates. Women received the
      drugs orally from week 38 of pregnancy to 1 week after delivery. Neonate therapy
      began 12 h after delivery and continued for 1 week. Both treatment regimens were
      well-tolerated in women and newborns. Lamivudine and zidovudine pharmacokinetics
      in pregnant women were similar to those in nonpregnant adults. Lamivudine and
      zidovudine freely crossed the placenta and were secreted in breast milk. Neonatal
      lamivudine clearance was about half that in pediatric patients; zidovudine
      clearance was consistent with previous reports. HIV-1 RNA could be quantified in
      17 of the 20 women. At the onset of labor/delivery, mean virus load had decreased
      by approximately 1.5 log10 copies/mL in both treatment cohorts. Although not
      definitive for HIV-1 infection status, all neonates had HIV-1 RNA levels below
      the limit of quantification at birth and at ages 1 and 2 weeks.

PMID- 9780253
TI  - Cervical human immunodeficiency virus type 1 shedding is associated with genital
      beta-chemokine secretion.
AB  - Forty human immunodeficiency virus type 1 (HIV-1)-infected women participated in
      a cross-sectional study of possible correlations between chemokine receptor (CCR5
      and/or CCR2B) genotype, HIV-1 RNA and DNA load, and beta-chemokine levels
      (RANTES, MIP-1alpha, MIP-1beta) in blood and cervix. HIV-1 nucleic acid and beta
      chemokines were found in all patient blood samples and in more than half of the
      cervical samples regardless of CCR5 or CCR2B genotype. High beta-chemokine
      concentrations were in general associated with high virus loads in blood and
      cervix. In the blood, the proviral DNA load was significantly correlated with the
      MIP-1alpha concentration, whereas the DNA load in cervix was significantly
      associated with the MIP-1beta concentration. The cervical viral RNA load was
      significantly associated with levels of all three chemokines. Thus, when HIV-1
      shedding was highest in the genital tract, it was associated with other
      combinations of beta-chemokines than virus load in blood, suggesting that local
      immune reactions strongly influence virus load in the cervical compartment.

PMID- 9780254
TI  - A human immunodeficiency virus (HIV)-inducing factor from the female genital
      tract activates HIV-1 gene expression through the kappaB enhancer.
AB  - Virus-enhancing factors present in the female genital tract may influence the
      transmission of human immunodeficiency virus type 1 (HIV-1). Previously, the
      presence of a heat-stable soluble factor in the cervicovaginal lavage (CVL) fluid
      of both HIV-infected and -uninfected women that induces HIV-1 expression in T
      cells and monocytes was reported. Now this CVL factor was shown to increase HIV-1
      gene expression through the activation of the kappaB enhancer in the viral long
      terminal repeat (LTR). DNA binding studies, together with functional studies
      using mutant LTR reporter constructs, indicate the requirement for an NF-kappaB
      dependent pathway in the CVL-mediated activation of HIV-1 expression. CVL samples
      that activated HIV-1 expression also stimulated AP-1-dependent transcription.
      These data demonstrate that an HIV-inducing factor, distinct from heat-labile
      cytokines, present in the female genital mucosa can activate AP-1 and NF-kappaB
      and increase HIV-1 gene expression through the kappaB enhancer, possibly
      contributing to HIV-1 transmission.

PMID- 9780255
TI  - Effect of human immunodeficiency virus type 1 infection upon acute salpingitis: a
      laparoscopic study.
AB  - To determine the effect of human immunodeficiency virus type 1 (HIV-1) infection
      upon pelvic inflammatory disease (PID), a laparoscopic study of acute PID was
      conducted in Nairobi, Kenya. Subjects underwent diagnostic laparoscopy, HIV-1
      serology, and testing for sexually transmitted diseases. Of the 133 women with
      laparoscopically verified salpingitis, 52 (39%) were HIV-1-seropositive. Tubo
      ovarian abscesses (TOA) were found in 33% of HIV-1-infected and 15% of HIV-1
      uninfected women (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.2-6.5).
      Among seropositive women, TOA was found in 55% of those with CD4 cell percent
      <14% vs. 28% with CD4 cell percent>14% (OR 3.1, 95% CI 0.6-15.3). Neisseria
      gonorrhoeae was detected in 37 women (28%) and Chlamydia trachomatis in 12 (9%);
      neither was significantly related to HIV-1 seropositivity. Length of
      hospitalization was not affected by HIV-1 serostatus overall but was prolonged
      among HIV-1-infected women with CD4 cell percent <14%. Among patients with acute
      salpingitis, likelihood of TOA was related to HIV-1 infection and advanced
      immunosuppression. In general, HIV-1-seropositive women with acute salpingitis
      responded well to treatment.

PMID- 9780257
TI  - Successful treatment of diarrheal disease associated with enteroaggregative
      Escherichia coli in adults infected with human immunodeficiency virus.
AB  - The presence of enteroaggregative Escherichia coli (EAggEC) in stool has been
      strongly associated with persistent diarrhea. No treatment trials have been done
      to demonstrate that clearance of EAggEc results in an improvement of diarrheal
      symptoms. Twenty-four adults infected with the human immunodeficiency virus (HIV)
      with diarrhea and EAggEC were randomized to a double-blind placebo-control cross
      over treatment trial (ciprofloxacin 500 mg orally twice daily for 7 days vs.
      placebo). After treatment with ciprofloxacin, the subjects had significantly
      fewer (50%) stools per day (from 5.0+/-2. 9 to 2.4+/-1.9). Intestinal symptoms
      decreased by 42% after active treatment. EAggEc were eradicated from stool of all
      participants after active treatment. These data strengthen the link between the
      presence of the EAggEc in stool and their role in the pathogenesis of diarrheal
      disease. It is likely that EAggEc are a treatable cause of diarrheal disease in
      some persons with HIV and no other apparent enteric pathogen.

PMID- 9780256
TI  - Chimeric influenza virus replicating predominantly in the murine upper
      respiratory tract induces local immune responses against human immunodeficiency
      virus type 1 in the genital tract.
AB  - Previously, a mucosal model of immunization against human immunodeficiency virus
      type 1 (HIV-1) was established by using influenza virus as a vector for the
      neutralizing gp41 epitope ELDKWA. Whether replication of this chimeric influenza
      virus in the upper respiratory tract of mice is sufficient for inducing mucosal
      immune responses in the genital tract was investigated. An immunization strategy
      was established that permits the virus to replicate in the murine upper
      respiratory tracts but not in the lungs. Intranasal application of the chimeric
      virus induced HIV-1-specific antibodies in sera and genital tract. In addition,
      chimeric virus-specific antibody-secreting cells were detected in lymphocyte
      populations obtained from lungs, spleens, and urogenital tracts. These results
      indicate that replication of the chimeric influenza/ELDKWA virus in the upper
      respiratory tract is sufficient to induce systemic immune responses as well as
      local immune responses in the genital tract.

PMID- 9780259
TI  - Type I Helicobacter pylori shows Lewis(b)-independent adherence to gastric cells
      requiring de novo protein synthesis in both host and bacteria.
AB  - Type I Helicobacter pylori strains frequently recognize the Lewisb (Leb) blood
      group antigen. This binding property and expression of the Leb oligosaccharide
      were required for adherence to fixed normal or pathologic gastric tissue. In
      contrast, both type I and type II strains adhered to cultured cells in the
      absence of the Leb epitope. For the gastric cell line AGS, adherence was
      significantly higher when viable type I strains were allowed to interact with
      viable AGS cells compared with fixed cells. The observation that chloramphenicol
      and cycloheximide, inhibitors of bacterial and eukaryotic protein synthesis,
      respectively, significantly reduced adherence of type I but not type II isolates
      suggests that in type I strains, adherence depends on the up-regulation of one or
      more host cell receptors triggered by the bacterium.

PMID- 9780258
TI  - Enterotoxic effect of the vacuolating toxin produced by Helicobacter pylori in
      Caco-2 cells.
AB  - Preliminary clinical evidence suggests that Helicobacter pylori may be associated
      with diarrhea through its vacuolating toxin (VacA). To establish whether VacA
      induces intestinal secretion, epithelial damage, or both, purified pH-activated
      VacA was added to Caco-2 cell monolayers mounted in Ussing chambers, and
      electrical parameters were monitored. Mucosal addition of VacA induced an
      increase in short circuit current, consistent with enterotoxic effect. The effect
      was time- and dose-dependent and saturable. It was not found if the toxin was not
      pH-activated, added to the serosal side, or preheated. In cells preloaded with
      the Ca2+ buffering compound BAPTA/AM or with the Cl- channel inhibitor 5-nitro-2
      3-(3-phenylpropylamino)benzoic acid, short circuit current did not change,
      indicating that VacA induces activation of Ca2+-dependent Cl- channels. VacA did
      not show cytopathic effects, as judged by tissue resistance. These results
      support the hypothesis that H. pylori may be associated with diarrhea through
      production of VacA.

PMID- 9780260
TI  - Full-length sequence analysis of the vacA gene from cytotoxic and noncytotoxic
      Helicobacter pylori.
AB  - Some clinical isolates of Helicobacter pylori fail to express vacuolating
      cytotoxin, despite possessing a copy of the vacA gene on the chromosome. To gain
      insight into the differences between vacA from cytotoxic and noncytotoxic
      strains, the vacA open-reading frames from 16 cytotoxic and 22 noncytotoxic
      strains were sequenced. Mutations that cause truncation of VacA in 11 of 22
      noncytotoxic strains were identified, including internal duplication, large
      deletion, 1-bp insertion, and non-sense mutations. In contrast, none of the 16
      cytotoxic strains had any truncation of VacA. Four cytotoxic strains had inserted
      sequences downstream of vacA. Three were mini-IS605, and the other was a putative
      rfaJ gene that encodes lipopolysaccharide glucosyltransferase. The rfaJ gene
      identified in this study had a poly(C) tract, resulting in premature termination
      of the gene product. The phylogenetic tree based on the vacA open-reading frame
      indicated that two different H. pylori lineages are circulating in Japan and the
      West.

PMID- 9780261
TI  - Vaccination of gnotobiotic piglets against Helicobacter pylori.
AB  - To determine the effect of oral adjuvant-assisted and parenteral vaccination,
      germ-free piglets were vaccinated orally with and without labile toxin adjuvant
      or parenterally and challenged with viable Helicobacter pylori. All prechallenge
      vaccination regimens induced anti-H. pylori antibodies and suppressed bacterial
      colonization, but no vaccination regime completely prevented infection.
      Parenteral vaccination given after infection had no effect on bacterial
      colonization. Lymphocytic gastritis was present in all piglets challenged with
      live bacteria regardless of vaccination status. Neutrophilic gastritis was
      present in vaccinated challenged piglets but not in infected, unvaccinated
      piglets. Gastritis was not present in uninfected control piglets regardless of
      vaccination status. In gnotobiotic piglets, vaccination suppresses but does not
      prevent infection by H. pylori, and parenteral vaccination does not cure infected
      piglets. Vaccination does not ameliorate gastritis due to H. pylori in piglets
      but does induce neutrophilic gastric inflammation in some infected piglets.

PMID- 9780262
TI  - Evaluation of the role of the Yersinia pestis plasminogen activator and other
      plasmid-encoded factors in temperature-dependent blockage of the flea.
AB  - Yersinia pestis, the plague bacillus, has a plasminogen activator (pla) gene on
      the 9.5-kb plasmid pPla that is hypothesized to play a role in producing the
      foregut blockage in the flea vector that precedes transmission. In this study,
      however, Y. pestis that lacked pPla, the 70-kb virulence plasmid, or both
      plasmids, proved able to block Xenopsylla cheopis fleas normally. Blockage rates
      decreased with increasing environmental temperature for fleas infected with
      either wild type or pPla- Y. pestis. Thus, procoagulant ability of the Y. pestis
      pla gene product does not mediate blockage, nor does its ability to induce
      fibrinolysis at>28 degreesC account for failure to block at elevated
      temperatures. A Y. pestis strain that lacked all or part of the third plasmid of
      110 kb, however, failed to colonize the flea midgut normally, indicating that one
      or more genes on the large plasmid may be required for vectorborne transmission.

PMID- 9780263
TI  - Generation and testing of mutants of Enterococcus faecalis in a mouse peritonitis
      model.
AB  - A previously described mouse peritonitis model was used to study derivatives of
      Enterococcus faecalis strain OG1RF. The addition of sterile rat fecal extracts
      (SRFE) lowered the LD50 of OG1RF >10-fold. Hemolysin production caused a 35-fold
      lower LD50 and a much shorter survival, similar to previous results using a
      peritonitis model without SRFE. A purine (but not a pyrimidine) auxotroph was
      considerably less lethal than wild type; gelatinase mutants were also attenuated.
      A suicide vector was generated with an enterococcal selectable marker in order to
      disrupt a gene encoding an E. faecalis antigen; the resulting mutant was not
      attenuated despite a slower growth rate. In conclusion, this model allows
      attenuated mutants to be detected, corroborates prior reports that hemolysin is a
      virulence factor, and suggests a role for gelatinase in virulence of E. faecalis
      in mice; the attenuated purine auxotroph may provide a system for developing
      vectors for in vivo expression systems.

PMID- 9780264
TI  - Monocyte anergy in septic shock is associated with a predilection to apoptosis
      and is reversed by granulocyte-macrophage colony-stimulating factor ex vivo.
AB  - The effects of priming monocytes from septic patients with granulocyte-macrophage
      colony-stimulating factor (GM-CSF) ex vivo were investigated. Monocytes from
      septic patients had depressed plasma GM-CSF and dysregulated levels of other
      cytokines compared with normal subjects. Membrane expression of CD71 and HLA-DR
      were depressed, and monocytes were anergic to lipopolysaccharide (LPS)
      stimulation in vitro, which was associated with spontaneous and accelerated
      activation-induced apoptosis by LPS. Priming monocytes with GM-CSF ex vivo
      augmented membrane cytokine expression, CD71, and HLA-DR. GM-CSF priming
      augmented cytokine secretion in response to LPS stimulation, restored cytokine
      secretion in monocytes from septic patients, and reversed their predilection to
      undergo apoptosis. Thus, monocyte dysfunction in septic shock is associated with
      depressed plasma levels of GM-CSF and enhanced apoptosis; however, GM-CSF
      stimulation ex vivo restored normal monocyte function and cytokine secretion by a
      mechanism that may depend on abrogating apoptosis.

PMID- 9780265
TI  - Enhanced responses to Mycobacterium tuberculosis antigens by human alveolar
      lymphocytes during active pulmonary tuberculosis.
AB  - Responses to mycobacterial and nonmycobacterial antigens were examined in
      bronchoalveolar cells (BAC) and peripheral blood mononuclear cells (PBMC) from
      patients with active pulmonary tuberculosis (n=16) and healthy subjects (n=23).
      DNA synthesis in BAC (but not PBMC) from tuberculosis patients was significantly
      increased in response to the mycobacterial antigens purified protein derivative
      (PPD), antigen 85, and mannose-capped lipoarabinomannan but not to
      nonmycobacterial antigens. The response to PPD was also increased in enriched
      alveolar lymphocytes from tuberculosis patients (P<.05). The frequency of
      interferon-gamma but not interleukin-4- or -10-producing cells by ELISAspot was
      increased in PPD-stimulated BAC from patients with tuberculosis (P<.05).
      Accessory function of alveolar macrophages for T lymphocyte responses was similar
      and suppressive activity was variably decreased in tuberculosis patients. Thus,
      there is compartmentalization of mycobacterial antigen-specific lymphocytes to
      the lungs during active tuberculosis that on challenge produce a Th1-type
      cytokine host response.

PMID- 9780266
TI  - Eradication of AIDS-related disseminated mycobacterium avium complex infection
      after 12 months of antimycobacterial therapy combined with highly active
      antiretroviral therapy.
AB  - To determine if microbiologic cure of AIDS-related disseminated Mycobacterium
      avium complex (MAC) is possible in patients receiving highly active
      antiretroviral therapy (HAART), 4 patients with a history of disseminated MAC
      received >/=12 months of macrolide-based antimycobacterial therapy. All were
      asymptomatic and had absolute CD4 cell count >100/microL (range, 137-301) and
      <10,000 copies/mL of human immunodeficiency virus RNA (range, <500-1250). A bone
      marrow aspirate and peripheral blood were obtained for mycobacterial culture.
      Follow-up blood cultures were obtained routinely at 4 weeks and every 8 weeks
      thereafter. All 4 patients had negative bone marrow and blood cultures and then
      discontinued antimycobacterial therapy. All patients' subsequent cultures remain
      sterile and all are clinically asymptomatic (range, 8-13 months follow-up). It
      appears that disseminated MAC infection can be cured by prolonged
      antimycobacterial therapy in some persons who experience sustained CD4 lymphocyte
      increases while receiving HAART.

PMID- 9780267
TI  - Mycobacterium-mediated chemokine expression in pleural mesothelial cells: role of
      C-C chemokines in tuberculous pleurisy.
AB  - Pulmonary tuberculosis is characterized by granulomatous inflammation with an
      extensive infiltration of mononuclear phagocytes, but the mechanisms of phagocyte
      recruitment to the pleural space is unknown. In this study, pleural fluid from
      patients with tuberculosis contained significantly (P<.001) more biologically
      active MIP-1alpha and MCP-1 (C-C cytokines) than did effusions from patients with
      congestive heart failure. Antigenic MIP-1alpha and MCP-1 was detected by
      immunocytochemistry in pleural biopsy sections of patients with tuberculous
      pleurisy. In vitro, pleural mesothelial cells stimulated with bacille Calmette
      Guerin (BCG) or interferon (IFN)-gamma produced MIP-1alpha and MCP-1. Reverse
      transcription-polymerase chain reaction studies confirmed that both BCG and IFN
      gamma induced MIP-1alpha and MCP-1 expression in mesothelial cells, demonstrating
      that mesothelial cell-derived C-C chemokines play a biologically important role
      in the recruitment of mononuclear cells to the pleural space.

PMID- 9780268
TI  - Epidemic leptospirosis associated with pulmonary hemorrhage-Nicaragua, 1995.
AB  - In October 1995, epidemic "hemorrhagic fever," without jaundice or renal
      manifestations, was reported in rural Nicaragua following heavy flooding; 2259
      residents were evaluated for nonmalarial febrile illnesses (cumulative incidence,
      6.1%) and 15 (0.7%) died with pulmonary hemorrhage. A case-control study found
      that case-patients were more likely than controls to have ever walked in creeks
      (matched odds ratio [MOR], 15.0; 95% confidence interval [CI], 1.7-132.3), have
      household rodents (MOR, 10.4; 95% CI, 1.1-97.1), or own dogs with titers >/=400
      to Leptospira species (MOR, 23.4; 95% CI, 3.6-infinity). Twenty-six of 51 case
      patients had serologic or postmortem evidence of acute leptospirosis. Leptospira
      species were isolated from case-patients and potential animal reservoirs. This
      leptospirosis epidemic likely resulted from exposure to flood waters contaminated
      by urine from infected animals, particularly dogs. Leptospirosis should be
      included in the differential diagnosis for nonmalarial febrile illness,
      particularly during periods of flooding or when pulmonary hemorrhage occurs.

PMID- 9780269
TI  - Cryptococcus neoformans and Candida albicans regulate CD4 expression on human
      monocytes.
AB  - This study examined the capability of Candida albicans and Cryptococcus
      neoformans to modulate CD4 expression on human monocytes. C. albicans and an
      acapsular strain of C. neoformans induced higher levels of CD4 expression than
      encapsulated strains. Purified glucuronoxylomannan did not regulate CD4
      expression on monocytes, but down-regulation of CD4 expression compared with
      stimulation by acapsular C. neoformans alone was observed when
      glucuronoxylomannan was used in combination with acapsular C. neoformans. The
      ability of opsonic factors to facilitate fungal-mediated CD4 overexpression
      suggests that binding or internalization (or both) of the yeast cells is a
      critical event. Protein synthesis was required, excluding redistribution of the
      intracellular pool of CD4 receptors to the cellular surface as the sole possible
      mechanism. Results demonstrate a new effect of fungi on professional phagocytic
      cells and raise the possibility that modulation of CD4 could influence gp120
      mediated human immunodeficiency virus entry.

PMID- 9780270
TI  - Kinetic study of host defense and inflammatory response to Aspergillus fumigatus
      in steroid-induced immunosuppressed mice.
AB  - The sequential pathogenesis of pulmonary aspergillosis was studied and the role
      of inflammatory cytokines in host response to Aspergillus fumigatus was
      characterized in immunocompetent and immunosuppressed mice. Two distinct phases
      were observed in immunocompetent mice: First, an intense clearance of A.
      fumigatus occurred, possibly through alveolar macrophages and recruited
      neutrophils (PMNL), accompanied by rapid release of tumor necrosis factor-alpha,
      interleukin (IL)-6, and IL-1beta, and second, cellular and fungal debris were
      cleaned by recruited monocytes, cytokine production rapidly decreased, and
      pneumonia self-healed. In contrast, cortisone-treated animals had, first, an
      altered clearance of conidia and delayed cytokine production and inflammatory
      cell recruitment; second, an invasive process in lungs, recruitment of PMNL, and
      release of IL-6 and IL-1beta; and third, widespread tissue necrosis, sustained
      release of IL-6 and IL-1beta, further increases in PMNL trafficking but no
      monocyte recruitment, respiratory failure, and 100% mortality within 5 days.
      These insights may be useful in the development of new treatment strategies for
      pulmonary aspergillosis.

PMID- 9780271
TI  - Combination therapy with famciclovir and interferon-alpha for the treatment of
      chronic hepatitis B.
AB  - Interferon-alpha (IFN-alpha) treatment results in long-term remissions in only
      25%-40% of patients with chronic hepatitis B virus (HBV) infection. Famciclovir,
      the oral prodrug of penciclovir, inhibits HBV DNA replication. Five adults with
      chronic HBV infection in whom previous IFN-alpha therapy had failed were treated
      in a pilot study of overlapping IFN-alpha and famciclovir therapy totaling 20
      weeks. HBV DNA levels decreased by 0.9 log units during the initial 4-week period
      of famciclovir alone, followed by a further decrease of 1.8 logs during the
      middle 12-week period of combination therapy. HBV DNA rose by 0.9 log during the
      final 4-week period of IFN-alpha alone. Two patients cleared HBV DNA, and their
      liver disease improved by clinical and histologic criteria. The combination of
      famciclovir and IFN-alpha appeared to be at least additive in suppressing HBV
      DNA. Efficacy trials of combination therapy with famciclovir and IFN-alpha are
      warranted.

PMID- 9780272
TI  - Comparison of the prevalence of antibodies to human herpesvirus 8 (Kaposi's
      sarcoma-associated herpesvirus) in Brazil and Colorado.
AB  - The prevalence of human herpesvirus 8 (HHV-8; Kaposi's sarcoma [KS] herpesvirus)
      infection was determined by IFA in 297 persons living in Brazil and Colorado. The
      prevalence of antibody to HHV-8 in human immunodeficiency virus (HIV) type 1
      seropositive gay men with and without KS was similar in Brazil and Colorado. In
      Brazil, the prevalence of HHV-8 antibody was significantly greater in HIV-1
      seronegative gay men than in HIV-1-seronegative male intravenous drug users. HHV
      8-seropositive Brazilian gay men who had a clinical diagnosis of KS or who were
      infected with HIV-1 had significantly higher titers of HHV-8 antibody than did
      HHV-8-seropositive, HIV-1-seronegative Brazilian gay men. These findings provide
      further support for the association between HHV-8 infection and KS and suggest
      that, as in the United States, HHV-8 infection is transmitted sexually in Brazil.

PMID- 9780273
TI  - Direct human papillomavirus (HPV) sequencing method yields a novel HPV in a human
      immunodeficiency virus-positive Quebec woman and distinguishes a new HPV clade.
AB  - Papillomaviruses of supergroup A exhibit genital tropism and are best known as
      etiologic agents for benign and malignant cervical lesions in women. A polymerase
      chain reaction direct sequencing approach with P-33-labeled dideoxynucleotides
      was used to detect and type human papillomaviruses (HPVs) in cervical biopsies. A
      novel sequence was found in condylomatous specimens from a human immunodeficiency
      virus-positive French Canadian woman. The viral gene L1 was sequenced completely,
      yielding a novel HPV type of supergroup A, named JC9710. This is related to a
      previously described HPV type from New Mexico, CP8061, and to Colobus monkey
      papillomavirus 1. Sequence similarity searches and phylogenetic analyses with
      different software packages clustered the three viral types as a new clade, for
      which the next available number, A15, was proposed.

PMID- 9780274
TI  - Resistance mutations in protease and reverse transcriptase genes of human
      immunodeficiency virus type 1 isolates from patients with combination
      antiretroviral therapy failure.
AB  - High-density oligonucleotide arrays were used to determine the sequence of the
      protease (PR) and reverse transcriptase (RT) genes of human immunodeficiency
      virus type 1 isolates from 35 patients in whom combination therapy that included
      a protease inhibitor had failed. Isolates had a median of three PR mutations
      (range, none to six). Three isolates had no known resistance mutations in PR.
      Twelve isolates (34%) had two or fewer resistance mutations in PR. The most
      commonly observed PR mutations were L10I, V82A/T/F, and L90M. No mutations were
      observed at codons 30 or 48. Mutations at RT codons 215 and 184 were observed in
      the majority of isolates. These data suggest that therapy can fail in some
      patients with relatively few PR resistance mutations. Clinical failure in the
      absence of resistance mutations implies inadequate drug exposure due to
      pharmacologic factors or suboptimal patient adherence to drug therapy.

PMID- 9780275
TI  - Neutralization of syncytium-inducing primary isolates by sera from human
      immunodeficiency virus (HIV)-uninfected recipients of candidate HIV vaccines.
AB  - Most candidate human immunodeficiency virus (HIV)-1 vaccines induce antibodies
      that neutralize T cell line-adapted HIV-1 strains. Until recently, however, no
      neutralizing activity against primary HIV-1 isolates had been demonstrated in
      sera from human vaccinees. Since most candidate HIV-1 vaccines have been
      constructed from T cell line-adapted syncytium-inducing (SI) strains, experiments
      were done to test whether sera from recipients of SI-based vaccines could
      preferentially neutralize SI primary HIV-1 isolates. Various neutralization
      assays were performed with sera from volunteers receiving ALVACgp160MN and/or
      rgp120SF2. Neutralizing activity was detected against 4 of 8 SI primary isolates
      but against none of 5 non-SI primary isolates. The data suggest that, for the
      induction of neutralizing antibodies to a broad array of HIV-1 primary isolates,
      a polyvalent vaccine will be needed containing representatives of more than a
      single category of viruses.

PMID- 9780276
TI  - Diversification of subtype E human immunodeficiency virus type 1 env in
      heterosexual seroconverters from Northern Thailand.
AB  - The C2-V3 region of the human immunodeficiency virus (HIV)-1 env was determined
      from 15 northern Thailand seroconverters between 1993 and 1995. Similar sequences
      were also determined from 18 seroconverting injection drug users in Baltimore.
      All seroconverters from northern Thailand were infected with subtype E HIV-1 on
      the basis of env sequences. Intersubject viral DNA distances increased from 2.3%
      in asymptomatic HIV-1-infected subjects characterized between 1990 and 1992 to
      7.8% in these more recent seroconverters from Thailand. On the other hand,
      sequences from 18 seroconverters from Baltimore had a mean intersubject distance
      of 13.2%. The genetic diversity within HIV-1 subtype E in seroconverters in
      Thailand has increased significantly but is still less than that observed in HIV
      1 from seroconverters in the United States, where the epidemic of HIV-1 infection
      is more mature. These results suggest that continued monitoring of the molecular
      epidemiology of HIV-1 infection in Thailand will be important for HIV vaccine
      development and evaluation.

PMID- 9780277
TI  - Borrelia burgdorferi-infected, interleukin-6-deficient mice have decreased Th2
      responses and increased lyme arthritis.
AB  - Recently, interleukin (IL)-6 was shown to be one of the earliest factors that
      trigger the differentiation of naive T cells into effector Th2 cells in vitro.
      Lyme arthritis was studied in IL-6-deficient mice, since joint inflammation is
      influenced by the T helper cell response against Borrelia burgdorferi. Arthritis
      incidence increased in B. burgdorferi-infected IL-6-deficient mice compared with
      that in controls. Furthermore, splenocytes of B. burgdorferi-infected IL-6
      deficient mice produced significantly less IL-4 in response to Borrelia antigens
      than did C57BL/6 (B6) mice, and B. burgdorferi-specific IgG2b levels were
      significantly reduced in IL-6-deficient mice at 60 days of infection. These
      results extend previous in vitro observations by demonstrating an in vivo role
      for IL-6 in the differentiation of CD4 T cells toward a Th2 phenotype and further
      show that CD4 T cell responses influence murine Lyme arthritis.

PMID- 9780279
TI  - Helicobacter pylori urease significantly reduces opsonization by human
      complement.
AB  - The role of Helicobacter pylori urease in opsonization by human complement was
      investigated. H. pylori wild type strain N6 and isogenic mutants lacking either
      the large urease subunit (UreB) or an accessory urease protein (UreG) were
      incubated with different sera. C3b bound to the bacteria was measured by specific
      staining and flow cytometry. As compared with opsonization of N6 and the UreG
      lacking mutant, opsonization of the UreB-lacking mutant was significantly
      increased after incubation with sera from both H. pylori uninfected (P<.001) or
      infected (P<.05) persons. However, when sera from uninfected persons were used,
      effective opsonization of this mutant proved to be dependent mainly on the
      classical pathway of complement activation. Irrespective of the serum used,
      opsonization values were very low after selective inactivation of the classical
      or the alternative pathway. Reduced opsonization of the urease-expressing strains
      could, to some extent, result from degradation of bound C3b.

PMID- 9780278
TI  - Recombinant Helicobacter pylori urease activates primary mucosal macrophages.
AB  - Helicobacter pylori urease is absorbed into the gastric mucosa at sites of
      inflammation, but whether the enzyme activates mucosal macrophages is not known.
      Because mucosal macrophages differ phenotypically and functionally from blood
      monocytes, whether recombinant H. pylori urease (rUrease) activated purified
      lamina propria macrophages in vitro was investigated. rUrease (1-10 microgram/mL)
      induced primary mucosal macrophages to produce interleukin (IL)-1beta, IL-6, and
      tumor necrosis factor (TNF)-alpha but not IL-8 proteins in a dose-dependent
      manner (P<.05 to P<.001). Quantitative reverse transcriptase-polymerase chain
      reaction using capillary electrophoresis laser-induced fluorescence showed that
      rUrease (0.1-10 microgram/mL) also induced dose-dependent expression of IL-1beta,
      IL-6, and TNF-alpha but not IL-8 mRNA (P<.05), suggesting that rUrease-induced
      production of certain cytokines is regulated at the level of gene transcription.
      These findings indicate that the ability of H. pylori urease to activate mucosal
      macrophages, resulting in production of proinflammatory cytokines, may be
      involved in the pathogenesis of H. pylori-associated mucosal inflammation.

PMID- 9780280
TI  - Mycoplasma pneumoniae pneumonia in a mouse model.
AB  - To investigate the pathogenesis of acute Mycoplasma pneumoniae infection, BALB/c
      mice were anesthetized with metofane, and M. pneumoniae was introduced
      intranasally on days 0, 1, and 2. Mice were sacrificed on days 0-15. A
      histopathologic scoring system defined inflammatory changes in the lungs on a
      scale of 0-26 (least to most severe). Broth cultures were positive for all nasal
      passage and bronchoalveolar lavage (BAL) specimens. Histopathologic scores ranged
      from 0 to 21. The mean log10 (cfu/mL) were 4.1-6.4 on days 1-10 and >/=1.7 on
      days 13-15 for nasal passage and BAL specimens. Serum polymerase chain reaction
      was negative. ELISA for serum IgM and immunoblots for M. pneumoniae antibody were
      positive in 21 (62%) of 34 and 33 (97%) of 34 infected animals, respectively, at
      days 8-15. ELISA for IgG antibody was negative. This mouse pneumonia model can be
      used to study the immunologic and therapeutic responses to acute M. pneumoniae
      infection.

PMID- 9780281
TI  - Neutrophils from AIDS patients treated with granulocyte colony-stimulating factor
      demonstrate enhanced killing of Mycobacterium avium.
AB  - Neutrophils isolated from AIDS patients have demonstrated improved growth
      inhibition of Mycobacterium avium when incubated with exogenous granulocyte
      colony-stimulating factor (G-CSF). In this clinical study, 30 AIDS patients
      without M. avium infection were randomized to receive 5 days of treatment with
      rifabutin, G-CSF, or both agents. The M. avium killing capacity of neutrophils
      harvested from each patient before intervention, during (day 4), and after
      therapy (day 7) was assessed. The mean change in human immunodeficiency virus
      load in the group receiving G-CSF alone was -0.07 log of viral RNA. There was a
      90% reduction in M. avium growth after therapy for patients treated with G-CSF
      alone (P=.01), 59% for patients treated with both agents (P=.06), and 11% for
      patients treated with rifabutin alone (P=.84). Thus, neutrophils isolated from
      AIDS patients treated with G-CSF demonstrated a significant enhancement of
      killing of M. avium; there was no notable effect on virus load.

PMID- 9780282
TI  - Delineation of human antibody responses to culture filtrate antigens of
      Mycobacterium tuberculosis.
AB  - This study was undertaken to define the antigens in culture filtrates of actively
      replicating Mycobacterium tuberculosis that are recognized by antibodies from
      tuberculosis (TB) patients. Two-dimensional Western blots were probed with sera
      from healthy controls and TB patients that were preabsorbed with Escherichia coli
      lysates to deplete cross-reactive antibodies. Antibodies from TB patients
      recognized 26 of the >100 culture filtrate proteins, and the repertoire changed
      with disease progression. Only 12 of 26 antigens, including 3 proteins implicated
      in colonization and invasion by mycobacteria (MPT51, MPT32, and 85C), and 9 (as
      yet undefined proteins) were reactive with sera from TB patients with early
      noncavitary or cavitary disease. Eight additional antigens, including 4 undefined
      proteins, were recognized only by sera from a subset of patients with advanced
      cavitary disease. Studies suggest that 3 of the antigens recognized by sera from
      patients with early TB (85C, MPT32, and a 88-kDa protein) have strong
      serodiagnostic potential.

PMID- 9780283
TI  - Nocardia farcinica sternotomy site infections in patients following open heart
      surgery.
AB  - Although Nocardia farcinica surgical site infection outbreaks have been reported
      (though rarely), no source for these has been identified. From May 1992 through
      June 1993, 5 patients contracted N. farcinica sternotomy site infections
      following open heart surgery at hospital A. A case-control study comparing case
      patients (n=5) with open heart surgery patients without subsequent sternotomy
      site infections (n=50) identified as risk factors diabetes (4/5 vs. 11/50, P<.02)
      and exposure to a particular anesthesiologist (anesthesiologist A; 4/5 vs. 9/50,
      P<.01). Four case-patients' isolates and a hand isolate of anesthesiologist A had
      an identical ribotype pattern (strain 1); the remaining case-patient's isolate
      and multiple isolates from anesthesiologist A's hands and home had a different
      ribotype pattern (strain 2). An intensified hand-washing regimen, barriers
      (gloves, gowns), and cleaning of anesthesiologist A's house were associated with
      termination of the outbreak. This is the first reported nosocomial N. farcinica
      outbreak to document the source and person-to-person transmission
      epidemiologically and molecularly.

PMID- 9780285
TI  - Reply 

PMID- 9780284
TI  - Polymerase chain reaction (PCR) from ficoll-purified polymorphonuclear leukocytes
      for monitoring cytomegalovirus infections in renal allograft recipients: superior
      sensitivity and similar specificity compared with plasma PCR.

PMID- 9780286
TI  - Study of human herpesvirus 8 (HHV-8) variants from Kaposi's sarcoma in France: is
      HHV-8 subtype A responsible for more agressive tumors?

PMID- 9780288
TI  - Reply 

PMID- 9780287
TI  - Cefaclor and cefuroxime axetil in the treatment of otitis media--an alternative
      view.

PMID- 9780289
TI  - Molecular mimicry in Campylobacter jejuni lipopolysaccharides and the development
      of Guillain-Barre syndrome.

PMID- 9780290
TI  - Reply 

PMID- 9780291
TI  - Strains of Escherichia coli belonging to serogroups O157 and O55 express
      lipopolysaccharides that are structurally distinct and do not share common
      epitopes.

PMID- 9780294
TI  - Immunological competence and nutritional status in patients with lung cancer.
AB  - The rate of infection in patients with malignant disease is significantly higher
      than in patients with benign disease. To investigate whether immunological
      competence is impaired in patients with lung cancer, we assessed neutrophil
      function (chemotaxis, phagocytosis, bacterial killing activity, and superoxide
      production), monocyte function (phagocytosis and killing activity), lymphocyte
      subsets using flow cytometry, and proliferation of lymphocytes stimulated by
      phytohemagglutinin, concanavalin A, and pokeweed mitogen. Studies were performed
      on 22 untreated patients with lung cancer and 21 age-matched healthy volunteers.
      Nutritional status was assessed by Niederman's nutritional index. In patients
      with lung cancer neutrophil chemotaxis, monocyte phagocytosis and killing,
      proliferation of lymphocytes stimulated by phytohemagglutinin and concanavalin A,
      but not pokeweed mitogen, and the number of natural killer cells were
      significantly lower than in healthy volunteers, whereas gammadelta T cells were
      increased (p < 0.05). The mean score on Niederman's nutritional index was worse
      in patients than in healthy volunteers (p < 0.001). Our results suggest that the
      impaired immunological competence and undernutrition may be among the mechanisms
      causing increased susceptibility to infection in patients with lung cancer.

PMID- 9780293
TI  - Serum surfactant protein A levels in healthy individuals are increased in
      smokers.
AB  - Serum levels of surfactant protein A (SP-A) were studied in 237 healthy subjects
      in relation to sex, age, and smoking habits. SP-A values in male smokers were
      significantly higher than those in male nonsmokers (p < 0.001). The amount of
      cigarette smoking did not correlate significantly with SP-A values, however. SP-A
      values in young nonsmoking males and females were somewhat lower than those in
      older, but without significant difference. No significant difference in values
      was found between the sexes. We conclude that (1) smoking increases serum levels
      of SP-A, and (2) SP-A serum levels are not affected by age and sex.

PMID- 9780295
TI  - Tenascin is increased in epithelial lining fluid in fibrotic lung disorders.
AB  - Tenascin is an extracellular matrix glycoprotein increased immunohistochemically
      in tumorous and fibrotic lung tissues as demonstrated by immunohistochemistry. We
      hypothesized that in bronchoalveolar lavage (BAL) fluid also the tenascin
      concentration would be elevated in patients with various fibrotic lung disorders.
      The aim of our study was to investigate whether BAL fluid tenascin would be
      increased compared with serum tenascin in patients with usual interstitial
      pneumonia (UIP), sarcoidosis, and extrinsic allergic bronchioloalveolitis. For
      this purpose BAL fluid was collected from five patients with UIP, 12 patients
      with sarcoidosis, five patients with extrinsic allergic bronchioloalveolitis, and
      six patients in a control group. BAL fluid and serum tenascin concentrations were
      detected by the enzyme immunoassay method. The BAL fluid results were expressed
      as tenascin concentrations in the epithelial lining fluid (ELF), as estimated by
      the urea method. The ELF tenascin concentration was increased in the patients
      with fibrotic lung disorders relative to the control group (mean 0.12 microg/ml)
      and was highest in the UIP group (mean 5.72 microg/ml) and sarcoidosis group
      (mean 4.76 microg/ml). It is concluded that the tenascin concentration in the ELF
      is increased in patients with UIP, sarcoidosis, and extrinsic allergic
      bronchioloalveolitis, suggesting active synthesis of tenascin in the lower
      respiratory tract in such disorders.

PMID- 9780296
TI  - Mycobacterium avium-intracellulare pulmonary infection in patients without known
      predisposing lung disease.
AB  - We tried to characterize the clinical features and findings on chest high
      resolution computed tomography (HRCT) of patients with Mycobacterium avium
      intracellulare (MAI) pulmonary infection without known predisposing lung disease
      and with no immunodeficiency. We also aimed to clarify the small airway and
      alveolar inflammation using bronchoalveolar lavage (BAL) from the affected
      regions. MAI infection was diagnosed in 53 patients from respiratory samples,
      including sputum and materials obtained using a fiberoptic bronchoscope. None had
      a predisposing lung disease or immunodeficiency, as assessed by medical history,
      routine laboratory data, and previously normal chest radiographs and/or CT scans.
      The mean age of the 53 patients was 60 +/- 11 years, and 48 were nonsmoking
      females. They had few respiratory symptoms, although 42% had chronic paranasal
      sinusitis. Chest HRCT findings showed centrilobular small nodules and ectasia of
      small bronchi and/or bronchioles located mainly in segment (S) 2, 3, 4, and 5.
      S1, which is usually affected by pulmonary tuberculosis, was completely free of
      these opacities. The BAL study revealed that the predominant cells were activated
      T lymphocytes and neutrophils. The CD4+/CD8+ ratio increased significantly.
      Bacteriology was negative for other bacteria and fungi. Although our patients did
      not present with distinct respiratory symptoms, the regions affected by MAI
      showed a chronic inflammation of mainly neutrophils and activated T lymphocytes.
      The presence of chronic sinusitis may be merely coincidental. However, its high
      prevalence and the finding of bronchiectasis in chest HRCT raise the question of
      whether silent bronchiectasis may be a predisposition.

PMID- 9780300
TI  - Four-Periodicity in Leslie Matrix Models with Density Dependent Survival
      Probabilities.
AB  - Leslie matrix models with a wide range of density dependent survival probability
      functions pi are studied. It is shown that for all pi which lead to nonstationary
      behavior, the instability is introduced through a supercritical Hopf bifurcation
      and further, that the dynamics in the unstable parameter regions in most cases
      has a strong resemblance of 4-cycles, either exact or approximate. Even in the
      chaotic regime a qualitative character of 4-cycles is preserved. Copyright 1998
      Academic Press.

PMID- 9780297
TI  - Byssinosis: role of polymer length on the effect of tannin on the airway beta
      adrenergic receptor.
AB  - Tannin, isolated from cotton bracts and implicated in the pathogenesis of
      byssinosis, inhibits isoproterenol and forskolin-stimulated cAMP release from
      airway cells in part by decreasing cell surface beta-adrenergic receptor number
      and uncoupling the beta-adrenergic receptor from its stimulatory G-protein (Gs)
      and in part by inhibiting adenylyl cyclase activity. We have hypothesized that
      cotton tannin, because of its long polymer length, interacts with the hydrophobic
      binding pocket of the beta-adrenergic receptor and alters beta-adrenergic
      receptor binding and Gs coupling. In these studies, tannins of three different
      polymer lengths and molecular masses were isolated from cotton bracts using
      sequential Amicon ultrafiltration [molecular mass > 10, 000 (YM10 retentate),
      1,000-10,000 (YM10 filtrate), and 1,000-5,000 Da (YM2 retentate)]. The YM10
      retentate (25 microg/ml) decreased chloride secretion (Jnet = 1.11 +/- 0.28
      (control) to 0.59 +/- 0.18 microEq/cm2.h, p < 0.05, n = 6), decreased cell
      surface beta-adrenergic receptor number (18.0 +/- 1.8 (control) to 10.6 +/- 0.9
      fmol/mg protein, p < 0.02, n = 4), and inhibited forskolin-stimulated cAMP
      release (5,254 +/- 1,290 (control) to 2, 968 +/- 620 pmol/mg protein, p < 0.01, n
      = 8). In contrast, neither the YM10 filtrate nor the YM2 retentate had any effect
      on net chloride secretion, beta-adrenergic cell surface receptor number, or
      forskolin-stimulated cAMP release. We conclude that polymer length is essential
      for the effect of tannin on the beta-adrenergic receptor and on adenylyl cyclase.

PMID- 9780302
TI  - Pattern Formation and the Spatial Scale of Interaction between Predators and
      Their Prey.
AB  - We study interactions of predators and prey that are characterized by a scale
      difference in their use of space. Prey are assumed to occupy patches, forming a
      metapopulation with low migration among patches. Predators are homogeneously
      distributed over these patches, due to broad-scale foraging behavior or long
      range juvenile dispersal. The predator population thus exerts a globally uniform
      predation pressure on the prey subpopulations. Under these conditions a nonlinear
      predator functional response depending on local prey density leads to multiple
      equilibria that can occur for the same parameter values. These equilibria differ
      in the fraction of prey patches that are (nearly) empty. Equilibria with a larger
      fraction of empty prey patches are more stable. The system tends to approach
      equilibria with a sufficiently high number of empty prey patches, so that local
      and global population dynamics are stable. If unstable dynamics are observed at
      all, the fluctuations in local prey density exhibit predictable characteristics.
      Our main conclusion is that a nonlinear functional response of the predator to
      local prey density can induce the formation of static patterns in prey density
      and, hence, lead to stable local and global dynamics. It is shown that these
      results are sufficiently general to carry over to situations in which prey
      migration between patches does occur or the spatial domain occupied by the prey
      population is continuous instead of subdivided into patches. Copyright 1998
      Academic Press.

PMID- 9780303
TI  - Effects of Optimal Antipredator Behavior of Prey on Predator-Prey Dynamics: The
      Role of Refuges.
AB  - The influence of optimal antipredator behavior of prey on predator-prey dynamics
      in a two-patch environment is studied. One patch represents an open habitat while
      the other is a refuge for prey. It is assumed that prey maximize their fitness
      measured by the instantaneous per capita growth rate. In each patch population
      dynamics is described by the Lotka-Volterra time continuous model. The refuge is
      characterized by its protectiveness which is inversely related to the predation
      risk for prey, and the dependence of population dynamics on protectiveness is
      studied. It is shown that adaptive behavior of prey changes qualitative
      properties of the underlying Lotka-Volterra model due to the appearance of a
      bounded attractor. Adaptive prey behavior does not lead to a stable equilibrium
      but to the reduction of population fluctuations. Dynamic consequences of a
      limited carrying capacity of the refuge are also considered. Low refuge carrying
      capacity leads to stability of predator-prey dynamics while stability is lost
      when the carrying capacity of the refuge is high. Lastly, it is shown that
      optimal antipredator behavior of prey leads to persistence and reduction of
      oscillations in population densities. Copyright 1998 Academic Press.

PMID- 9780301
TI  - Environmental Variability and the Persistence of Parasitoid-Host Metapopulation
      Models.
AB  - Parasitoid-host metapopulation models (after Reeve) were simulated with varying
      amounts of spatio-temporal or spatial environmental variability, as well as
      varying dispersal rates and instability of within-population dynamics.
      Persistence with environmental variability occurred over broad ranges of low
      dispersal rates, the amount of variability required for persistence increased
      with increasing dispersal, and the range of values giving persistence was less
      when within-population dynamics where more unstable. Fixed spatial variation was
      found to be sometimes more effective than spatio-temporal variability at
      producing persistence, but with greater variance among replicates.
      Metapopulations also could persist without environmental variability (as found by
      Adler), but this occurred at very particular dispersal rates, quite different
      from those allowing persistence with environmental variability. Copyright 1998
      Academic Press.

PMID- 9780304
TI  - Activin A and follistatin regulate developmental competence of In vitro-produced
      bovine embryos.
AB  - The effects of activin A and/or follistatin on the development of bovine embryos
      were investigated. Presumptive zygotes matured and fertilized in vitro were
      cultured in a chemically defined medium (modified synthetic oviduct fluid medium;
      mSOF). Addition of 1-100 ng/ml of activin A to mSOF significantly increased the
      percentage of zygotes that developed to morulae and blastocysts (48-54% and 31
      41%, respectively) compared with no addition (41% and 25%, respectively). In
      contrast, addition of 1-100 ng/ml follistatin significantly reduced the
      percentage of zygotes developing to morulae and blastocysts (29-31% and 17-20%,
      respectively) compared with no addition (41% and 28%, respectively). In a culture
      with 10 ng/ml of activin A, supplementation with the same concentration of
      follistatin neutralized the positive effect of activin A, while supplementation
      with 100 ng/ml of follistatin reduced the percentage of zygotes that developed.
      The total cell numbers in morulae and blastocysts were not affected by the
      addition of activin A and/or follistatin. The development-enhancing effects of
      activin A and the development-impeding effects of follistatin were observed when
      embryos were exposed to activin A or follistatin at a concentration of 10 ng/ml
      prior to the 9- to 16-cell stage. These results suggest that activin A and
      follistatin may affect bovine embryos until the third cell cycle and may play
      important roles in regulation of the developmental competence of bovine embryos.

PMID- 9780305
TI  - Development and validation of a fecal testosterone biomarker in Mus musculus and
      Peromyscus maniculatus.
AB  - This is a report on the development and validation of an ELISA method to
      determine fecal testosterone levels, and on their evaluation as a biomarker for
      adverse effects of endocrine-disrupting chemicals on reproductive health using
      male rodents of the Peromyscus maniculatus and Mus musculus species as an animal
      model. The ELISA antibody had the highest specificity for testosterone (100%),
      followed by dihydrotestosterone (57.4%) and androstenediol (0.27%). Radiolabeled
      testosterone was injected i.p. into three mice. Fecal samples were collected,
      extracted, and analyzed by liquid scintillation counting. The ELISA was performed
      to characterize the excretion kinetics and metabolic fate of circulating
      testosterone. Solubilization of feces with 10% methanol overnight provided an
      extraction efficiency of 87% for all metabolites; an ethyl ether extraction was
      more selective for testosterone. The fecal excretion of the testosterone was a
      biphasic process with a majority of the radioactivity recovered in the first 24
      hours. HPLC analysis revealed at least five testosterone metabolites in feces,
      with most metabolites being less polar than testosterone. This study forms the
      initial evaluation of what will become a field monitoring tool.

PMID- 9780306
TI  - Potential contraceptive use of epididymal proteins: immunization of male rats
      with epididymal protein DE inhibits sperm fusion ability.
AB  - Rat epididymal protein DE associates with the sperm surface during maturation and
      participates in sperm-egg fusion. Immunization of male rats with DE raised
      specific antibodies and produced a significant reduction in the animals'
      fertility. The present study focused on determining the in vivo mechanism
      involved in fertility inhibition. Wistar males were injected with DE, and
      antibody levels and animal fertility were evaluated. Results revealed an
      association between the two parameters, since animals with absorbance values
      lower than 0.5 in ELISA presented high fertility rates (66%, 100%) while those
      with absorbance values higher than 0.5 exhibited the lowest fertility rates (0%,
      33%). Histological studies showed no evidence of orchitis, epididymitis, or
      vasitis in DE-immunized animals. ELISA results revealed the presence of anti-DE
      antibodies in epididymal and vas deferential fluids. Indirect immunofluorescence
      and ELISA experiments indicated that these antibodies would not interfere with
      the synthesis or secretion of DE or with its association with the sperm surface.
      Finally, while epididymal sperm recovered from DE-immunized animals presented no
      changes in motility, viability, or ability to undergo capacitation and acrosome
      reaction, they exhibited a significant decrease in their ability to fuse with
      zona-free eggs, with no effect on their ability to bind to the oolemma. Together
      these results indicate that immunization of male rats with epididymal protein DE
      specifically interferes with the sperm fertilizing ability, supporting the use of
      epididymal proteins for contraceptive vaccine development.

PMID- 9780308
TI  - Quantification of inhibin/activin alpha and betaA subunit messenger ribonucleic
      acid by competitive reverse transcription-polymerase chain reaction in chicken
      granulosa cells during follicular development.
AB  - The very sensitive quantitative competitive reverse transcription-polymerase
      chain reaction (RT-PCR) was used to investigate the expression of inhibin/activin
      subunits in the granulosa cells of developing ovarian follicles of the hen. Two
      competitors specific to inhibin alpha and betaA subunits were constructed. In one
      study, the expression of inhibin alpha and betaA genes was determined in the
      granulosa cells of the five largest yellow follicles (F1, F2, F3, F4/5), the
      small yellow follicles (SYF), and the large white follicles (LWF) of a layer
      strain of chickens. Competitive RT-PCR for inhibin alpha subunit revealed 10.35
      +/- 2.15 pg/ microg total RNA in the LWF. The expression increased 40-fold in the
      SYF and remained at that level in the F4/5 but decreased markedly thereafter up
      to the F1 stage. Inhibin/activin betaA subunit was also detected in the LWF in
      low amounts and showed no significant increase until the F2 stage. The highest
      level was found in the F1. The pattern of the mRNA for alpha and betaA subunits
      in the five largest follicles (F1, F2, F3, F4/5) of a broiler breeder strain of
      chicken was compared with that in the layer strain. Expression of the alpha
      subunit was significantly higher in the three largest follicles (F1, F2, F3) of
      the broiler breeder hens, but only in the F2 for the betaA. The results suggest
      that inhibin alpha may play an important role in the recruitment and
      differentiation of follicles and that differences between broiler breeders and
      layers may have consequences at both the pituitary and ovarian levels.

PMID- 9780307
TI  - Relative impact of oxidative stress on the functional competence and genomic
      integrity of human spermatozoa.
AB  - Reactive oxygen metabolites are known to disrupt sperm-oocyte fusion, sperm
      movement, and DNA integrity; however, the relative sensitivities of these
      elements to oxidative stress are unknown. In this study these factors were
      assessed in human spermatozoa exposed to increasing levels of oxidative stress
      achieved through the stimulation of endogenous oxidant generation with NADPH or
      direct exposure to hydrogen peroxide. At low levels of oxidative stress, DNA
      fragmentation was significantly reduced while the rates of sperm-oocyte fusion
      were significantly enhanced. As the level of oxidative stress increased, the
      spermatozoa exhibited significantly elevated levels of DNA damage (p < 0.001) and
      yet continued to express an enhanced capacity for sperm-oocyte fusion. At the
      highest levels of oxidative stress, extremely high rates of DNA fragmentation
      were observed but the spermatozoa exhibited a parallel loss in their capacities
      for movement and oocyte fusion. These studies emphasize how redox mechanisms can
      either enhance or disrupt the functional and genomic integrity of human
      spermatozoa depending on the intensity of the oxidative stimulus. Because these
      qualities are affected at different rates, spermatozoa exhibiting significant DNA
      damage are still capable of fertilizing the oocyte. These results may have long
      term implications for the safety of assisted conception procedures in cases
      associated with oxidative stress.

PMID- 9780309
TI  - Increased expression of the rat myometrial oxytocin receptor messenger
      ribonucleic acid during labor requires both mechanical and hormonal signals.
AB  - We investigated the expression of the mRNA encoding the oxytocin receptor (OTR)
      in rat myometrium throughout gestation and its regulation by progesterone and
      mechanical stretch. Using a semiquantitative reverse transcription-polymerase
      chain reaction approach, OTR mRNA was found to increase abruptly at the onset of
      spontaneous labor at term. Progesterone (4 mg/day) starting on Day 20 of
      gestation blocked this increase. Ovariectomy on Day 17 induced preterm labor 96 h
      after surgery and a significant increase in myometrial OTR mRNA levels 48 and 96
      h after surgery. Both preterm labor and the rise in myometrial OTR expression
      were blocked by progesterone. To investigate the effects of stretch on myometrial
      OTR mRNA expression, unilaterally pregnant rats underwent either sham operation
      or placement of a tube in the nongravid uterine horn to distend the myometrium.
      On Day 20, stretch had no effect on OTR expression in the nongravid horns. During
      labor, OTR mRNA was highly expressed in the gravid horns as well as the nongravid
      stretched horns. In contrast, the level remained low in the nongravid unstretched
      horns. These results indicate that expression of rat myometrial OTR mRNA during
      pregnancy and labor is regulated by coordinated interactions between mechanical
      and endocrine signals.

PMID- 9780310
TI  - Equine chorionic gonadotropin regulates luteal steroidogenesis in pregnant mares.
AB  - The onset of eCG secretion in pregnant mares coincides with an increase in luteal
      steroid production and a relative shift toward androgen and estrogen synthesis.
      However, a cause-effect relationship between eCG and the shift in luteal
      steroidogenesis has not been demonstrated. In this study, we have investigated
      the effect of eCG on steroid production by the corpus luteum (CL) during equine
      pregnancy. All mares were supplemented with 44 mg altrenogest (a progestogen) per
      day on Days 18-50. Increasing doses of eCG were administered on Days 26-28,
      before the onset of endogenous eCG secretion, to four mares with and four mares
      without a functional CL (prostaglandin F2alpha administered on Day 18). Four
      mares with a functional CL received no exogenous eCG. In eCG-treated mares
      without a functional CL, progestin, androstenedione, and estrogen concentrations
      did not significantly increase after exogenous eCG administration or endogenous
      eCG secretion. In eCG-treated mares with a functional CL, progestin and estrogen
      production increased significantly after exogenous eCG administration and
      endogenous eCG secretion, whereas androstenedione concentrations tended to
      increase following exogenous eCG and increased significantly following endogenous
      eCG secretion. In mares with a functional CL that did not receive exogenous eCG,
      progestin and estrogen concentrations increased and androstenedione
      concentrations tended to increase only after the onset of endogenous eCG
      secretion. These data demonstrate that the increase in luteal steroidogenesis
      that coincides with the onset of eCG secretion is induced by eCG and results in
      an increase in luteal androgen and estrogen synthesis. Our findings support the
      hypothesis that eCG has a luteotropic action in pregnant mares.

PMID- 9780312
TI  - The selective prostaglandin endoperoxide synthase-2 inhibitor, NS-398, reduces
      prostaglandin production and ovulation in vivo and in vitro in the rat.
AB  - Two isoforms of prostaglandin G/H synthase, PGS-1 and PGS-2, catalyze the
      formation of prostaglandins (PG). Nonselective PGS inhibitors, e.g.,
      indomethacin, reduce the number of ovulations and PG levels in many animal
      models. This study evaluated the effects of the selective PGS-2 inhibitor NS-398,
      compared to indomethacin, on ovulation number and on PG and steroid production
      both in vivo and in vitro in the rat. NS-398 reduced the synthesis of PGE2 in
      isolated, LH-stimulated preovulatory follicles incubated in vitro. The inhibition
      by NS-398 was similar to that of indomethacin. Maximal inhibition was noted from
      0.1 microM. Neither progesterone nor cAMP production was affected by NS-398 or
      indomethacin. The effect of in vivo administration of NS-398 (1, 3, or 10 mg/kg
      BW, s. c.) to proestrous rats 1 h after the injection of an ovulatory dose of hCG
      was monitored in follicles extirpated 10 h after hCG. These follicles were
      incubated in vitro, and NS-398 dose-dependently reduced PGE2 production. The
      synthesis of cAMP and progesterone was not altered. In separate experiments, the
      same doses of NS-398 were injected to determine their effect on ovulation in
      vivo. The number of ovulations was decreased by the highest dose of NS-398. In
      the in vitro ovarian perfusion model, NS-398 (10 microM) reduced the number of
      ovulations initiated by LH and isobutylmethylxanthine. Lower doses of NS-398 (0.1
      and 1 microM) were less effective. The production of prostanoids (PGE2,
      PGF2alpha, and 6-keto-PGF1alpha) was reduced in a dose-dependent manner by NS
      398. The secretion of steroids was not affected. This study demonstrates that
      selective inhibition of PGS-2 by NS-398 reduces LH/hCG-stimulated production of
      prostanoids and the number of ovulations both in vivo and in vitro. These results
      provide direct evidence to strengthen the role of the inducible, granulosa cell
      expressed PGS-2 as one of the key regulators in the ovulatory process and also
      document that the elevated and perhaps sustained levels of PG are obligatory for
      ovulation.

PMID- 9780311
TI  - Prostaglandin f2alpha treatment in vivo, but not in vitro, stimulates protein
      kinase C-activated superoxide production by nonsteroidogenic cells of the rat
      corpus luteum.
AB  - Luteal regression is associated with the generation of reactive oxygen species
      (ROS). To determine the nature of the ROS generator, cells isolated from
      luteinized rat ovaries were examined for ROS production using luminol-amplified
      chemiluminescence (LCL). Cells cultured for 2-48 h exhibited minimal LCL, but
      there was a significant (30- to 50-fold), rapid (maximum at 3-5 min), and dose
      dependent increase in LCL in response to phorbol ester (phorbol 12-myristate 13
      acetate; TPA; ED50 = 0.03 microM) and diacylglycerol (1,2-dioctanoyl-glycerol;
      ED50 = 30 microM). The TPA-induced response was cell number dependent and was
      virtually abolished by superoxide dismutase, freezing, or heating (95 degrees C
      for 5 min). Zymosan, known to induce a phagocytic response in leukocytes,
      stimulated a superoxide (O2-.) response with a slow onset (maximum at 40 to 60
      min) and a maximum about one third of that observed for TPA. The response to TPA
      and zymosan was inhibited by the NADPH/NADH-oxidase inhibitor, diphenylene
      iodonium (ID50 = 5 microM for TPA), but not by the mitochondrial inhibitors,
      potassium cyanide, rotenone, or sodium azide. Fractionation of cells by
      centrifugal elutriation showed that TPA-stimulated O2-. production coeluted with
      the nonsteroidogenic cells and that little, if any, O2-. generation coeluted with
      the steroidogenic cells. Cells isolated 1, 2, and 4 h after in vivo treatment
      with a luteolytic dose of prostaglandin F2alpha (PGF2alpha) showed a significant
      increase in TPA-stimulated O2-. production at 2 h, whereas luteal cells or
      corpora lutea incubated directly with 1 microM PGF2alpha did not show any
      increase in response. Corpora lutea isolated from naturally regressed ovaries (18
      days after ovulation) showed a significantly elevated level of TPA-stimulated O2
      . production. In conclusion, there is a superoxide generator in luteinized
      ovaries that is activated through a protein kinase C pathway, localized in
      nonsteroidogenic cells, transiently increased during PGF2alpha-induced luteolysis
      in vivo, and elevated during natural luteal regression.

PMID- 9780313
TI  - Abnormalities in functional development of the Sertoli cells in rats treated
      neonatally with diethylstilbestrol: a possible role for estrogens in Sertoli cell
      development.
AB  - Diethylstilbestrol (DES) was administered neonatally (Days 2-12; 10 microg on
      alternate days) to rats, and developmental changes in Sertoli cell function were
      evaluated at 18, 25, and 35 days of age and compared to those observed in rats
      administered a GnRH antagonist (GnRHa; Days 2 and 5; 10 mg/kg) or a vehicle
      (controls). DES and GnRHa treatments resulted in similar reductions in both
      Sertoli cell numbers (40% for DES, 48% for GnRHa) and suppression of testicular
      growth at 18 and 25 days, though by 35 days the suppression was more pronounced
      (p < 0.001) in DES-treated animals. Plasma FSH levels were suppressed markedly at
      18 and 25 days, but not at 35 days, in GnRHa-treated rats, whereas in DES-treated
      rats the FSH levels were suppressed significantly only at 35 days. Both
      treatments suppressed plasma levels of inhibin B, though this was more pronounced
      (p < 0.05) in DES- than in GnRHa-treated rats. In controls, Sertoli cell
      immunoexpression of inhibin alpha, sulfated glycoprotein-1 (SGP-1), and androgen
      receptor (AR) increased in intensity and changed to an adult, stage-dependent
      pattern by 25 days. In GnRHa-treated rats these changes were reduced in intensity
      but were similar to those in controls at 35 days. In DES-treated rats, the
      increase in intensity and stage-dependent pattern of immunoexpression of inhibin
      alpha, SGP-1, and AR were virtually absent at 25 days but were present by 35
      days. Germ cell volume per Sertoli cell was reduced in GnRHa- and DES-treated
      rats compared with controls at 18 and 25 days but was significantly greater (p <
      0. 001) in DES- than in GnRHa-treated rats at 35 days. The proportion of
      apoptotic to viable germ cells was increased (p < 0.01) in GnRHa- and DES-treated
      rats compared with controls at 18 and 25 days; but at 35 days, values in GnRHa
      treated rats had declined to control values whereas those for DES-treated rats
      remained 10-fold elevated (p < 0.001). In adulthood, testis weight and daily
      sperm production were reduced by 43% and 44%, respectively, in GnRHa-treated
      rats, but spermatogenesis was grossly normal. Comparable changes were observed in
      approximately 25% of DES-treated rats, but the majority exhibited > 60% reduction
      in testis weight with many Sertoli cell-only tubules and very low daily sperm
      production. Taken together, these data are interpreted as providing evidence for
      direct modulation of Sertoli cell (maturational) development by DES.

PMID- 9780314
TI  - Recombinant fertilization antigen-1 causes a contraceptive effect in actively
      immunized mice.
AB  - Recombinant (r) fertilization antigen (FA)-1 was investigated for its
      immunocontraceptive effect using the mouse as a model. Active immunization with
      the murine rFA-1 antigen raised high antibody titers in all the immunized mice (n
      = 16 in two trials); these titers were long lasting and reached preimmunization
      levels by the 255th day. There was a significant (p < 0.0001) effect (64%
      reduction in trial I and 70% reduction in trial II) in fertility of immunized
      animals compared to PBS-control animals (n = 22 in two trials). The effect on
      fertility was reversible. When the antibody titers declined to control levels,
      all the animals conceived and delivered healthy babies without a significant (p >
      0.05) effect on the litter size compared to that of controls. There was a
      significant (p = 0.025) correlation (r = 0.76) between the reduction in fertility
      and the circulating rFA-1 antibody titers. Anti-rFA-1 antibodies from immunized
      mice, and not the immunoglobulins from the PBS-control mice, significantly (p <
      0.001) blocked murine sperm binding to zona pellucida and in vitro fertilization
      of murine oocytes. In a Western blot procedure, the anti-rFA-1 antibodies
      specifically recognized the protein band of approximately 47 kDa (dimeric form of
      cognate FA-1 antigen) only in the protein extract of testes and not in the
      extracts of somatic tissues tested, namely kidney, liver, intestine, spleen,
      muscle, heart, lung, brain, and ovary. In conclusion, our data indicate that
      active immunization with rFA-1 antigen induces a strong and sperm/testis-specific
      antibody response that causes a reversible inhibition of fertility by affecting
      sperm-zona binding and the fertilization process. These findings suggest that rFA
      1 antigen is an exciting candidate for the development of a contraceptive
      vaccine.

PMID- 9780315
TI  - Mesotocin receptor gene and protein expression in the prostate gland, but not
      testis, of the tammar wallaby, Macropus eugenii.
AB  - Evidence suggests that systemic oxytocin (OT) causes contractions of the prostate
      gland during ejaculation in eutherians, although functional OT receptors in this
      tissue have not been identified. Male marsupials secrete mesotocin (MT) from the
      pituitary and have relatively large, muscular prostate glands, so we examined MT
      receptors (MTRs) in the reproductive tract of the male tammar wallaby at the mRNA
      and protein level. We first obtained a partial (588 base pair) sequence of the
      tammar MTR cDNA that showed high homology to eutherian OT receptors (74-77%) and
      low homology to vasopressin receptors (38-52%). Analysis by reverse transcription
      polymerase chain reaction demonstrated MTR mRNA in the adult, juvenile, and pouch
      young prostate and epididymis, but not testis. MTR transcripts were observed in
      the smooth muscle layers surrounding the urethral lumen and in the fibromuscular
      capsule. There was a single high-affinity 125I-D(CH2)5[Tyr(Me)2, Tyr4, Orn8, Tyr
      NH29]-vasotocin (125I-OTA) binding site in the adult prostate. Competitive
      binding assays revealed identical ligand-binding profiles to the myometrium MTR
      (OTA > OT = MT > arginine vasopressin [AVP] antagonist > AVP). A lower-affinity
      125I-OTA-binding site was present in the testis, with ligand-binding profiles
      indicating binding to vasopressin receptors. MTR concentrations in the prostate
      were 8-fold lower than concentrations in the myometrium. Our data demonstrate the
      presence of an MTR gene and functional receptor protein in the prostate gland,
      but not the testis, of the tammar. Localization of MTRs to the smooth muscle
      fibers in the capsule and surrounding the urethral lumen suggests a contractile
      function for MT during ejaculation.

PMID- 9780316
TI  - Chronic oxytocin pretreatment inhibits adenylyl cyclase activity in cultured rat
      myometrial cells.
AB  - To determine whether chronic oxytocin pretreatment inhibits adenylyl cyclase, we
      compared adenylyl cyclase activity in membranes prepared from cultured,
      immortalized rat myometrial cells that were untreated or pretreated for 24 h with
      oxytocin. Chronic oxytocin pretreatment (1 x 10(-5) M for 24 h) attenuated basal,
      guanosine triphosphate (1 x 10(-5) M)-, isoproterenol (1 x 10(-4) M)-, forskolin
      (1 x 10(-5) M)-, MnCl2 (20 mM)- or NaF (1 x 10(-2) M)-stimulated adenylyl cyclase
      activity by 27 +/- 5% to 39 +/- 11% (n = 6, p < 0.05). Oxytocin pretreatment for
      2 h (n = 5) did not produce a significant effect. To understand the mechanism by
      which oxytocin pretreatment decreased activity of the adenylyl cyclase pathway,
      we compared effects of pretreatment with either oxytocin or phenylephrine on
      adenylyl cyclase activity and determined the effects of Gi inhibition and protein
      kinase C (PKC) depletion. Chronic (24 h) phenylephrine pretreatment (1 x 10(-4)
      M) had effects similar to those of oxytocin pretreatment (1 x 10(-5) M). PKC
      depletion with phorbol 12-myristate 13-acetate (1 x 10(-6) M, 41 h) prevented
      attenuation of adenylyl cyclase activity by oxytocin pretreatment (1 x 10(-5) M
      for 24 h). Inhibition of Gi by pertussis toxin pretreatment (1.25 microg/ml, 41
      h) had no significant effect. These findings suggest that chronic oxytocin
      pretreatment desensitizes the adenylyl cyclase pathway by a cross-regulatory
      mechanism that involves activation of Gq and PKC.

PMID- 9780317
TI  - Regulation of luteinizing hormone receptor gene expression by insulin-like growth
      factor-I in an immortalized murine Leydig tumor cell line (BLT-1)
AB  - It is postulated that insulin-like growth factor-I (IGF-I), a 70-amino acid
      mitogenic polypeptide, regulates Leydig cell steroidogenesis. In the present
      study, we assessed the effect of IGF-I on LH receptor (LHR) gene expression in an
      immortalized murine Leydig tumor cell line (BLT-1). Culture of BLT-1 cells in the
      presence of IGF-I (0.1-100 ng/ml) for 24 or 48 h increased their [125I]iodo-hCG
      binding in a dose-dependent manner up to 275% of the control level. Northern
      hybridization analysis revealed four major transcripts of LHR mRNA in BLT-1 cells
      (6.9, 2.6, 1.7, and 1.2 kilobases), and treatment at 10-100 ng/ml of IGF-I
      increased steady-state levels of LHR mRNAs in coordinate fashion up to 2. 2-fold.
      IGF-I (30 ng/ml) induced a time-dependent increase in [125I]hCG binding after a
      lag period of 2-6 h when studied up to 48 h, with a subsequent decrease. A
      similar response with steady increase up to 72 h was observed in total LHR mRNA.
      To elucidate the molecular mechanism of IGF-I action on LHR mRNA expression, we
      measured the transcription rate of the LHR gene by nuclear run-off assay and
      assessed transcript stability by the actinomycin D blocking method. The results
      showed that IGF-I treatment had no effect on the transcription rate of the LHR
      gene, whereas the half-life (t1/2) of LHR mRNA was significantly prolonged (IGF-I
      treated cells, 30 +/- 3.8 h; controls, 17 +/- 2.5 h). Furthermore, IGF-I at 30
      ng/ml and 100 ng/ml increased the expression of LHR promoter-driven luciferase
      and cytomegalovirus-promoter driven ss-galactosidase activities in BLT-1 cells;
      however, the former increased only marginally more than the latter. This suggests
      that the increase of LHR mRNA by IGF-I in Leydig cells is mainly due to increased
      mRNA stability.

PMID- 9780318
TI  - Excitatory amino acid regulation of gonadotropin secretion in prepubertal heifer
      calves.
AB  - The mechanisms controlling the pulsatile release of gonadotropins in prepubertal
      heifers are not completely understood. We examined the role of excitatory amino
      acid neurotransmitters, via activation of N-methyl-D-aspartate (NMDA) receptors,
      in the control of pulsatile LH and FSH release during prepubertal development in
      heifers. Hereford heifer calves received 4.7 mg/kg of N-methyl-D,L-aspartic acid
      (NMA), a potent NMDA receptor agonist (n = 5, i.v.), or saline (n = 5, i.v.), as
      single doses, at 4, 8, 12, 24, 36, and 48 wk of age. Blood samples were collected
      every 15 min, for 1 h before and 9 h after injection, on the days of treatment.
      Injection of NMA resulted in an acute release of LH (p < 0.001) in 0, 3, 3, 4, 5,
      and 5 calves (p < 0.01) and of FSH (p < 0.001) in 0, 1, 2, 4, 3, and 2 calves at
      4, 8, 12, 24, 36, and 48 wk of age, respectively. The peak response of LH and FSH
      release to NMA was at 15 min posttreatment, and these peak responses were highest
      at 36 wk of age (p < 0.05). We suggest that neuroexcitatory amino acids, through
      NMDA receptors, are involved in prepubertal development of LH and FSH secretion
      in heifer calves.

PMID- 9780319
TI  - Up-regulation of oxytocin receptor messenger ribonucleic acid and protein by
      estradiol in the cervix of ovariectomized rat.
AB  - Oxytocin receptor (OTR) regulation has been extensively studied in uterine
      myometrium and endometrium. However, studies in the cervix are limited. The
      present studies utilized in situ hybridization and immunocytochemistry to
      localize OTR mRNA and protein distribution in cervices of nonpregnant
      ovariectomized (OVX) rats and examined the effect of combined and independent
      treatments with estradiol and progesterone on cervical OTR. Thirteen nonpregnant
      rats were bilaterally OVX under general anesthesia. At least 7 days later, the
      rats were exposed to one of four different treatments 24 h prior to necropsy: 1)
      estradiol (50 microg, n = 4); 2) progesterone (10 mg, n = 3); 3) both estradiol
      (50 microg) and progesterone (10 mg) (n = 3); 4) corn oil vehicle (n = 3). After
      24-h estradiol treatment, OTR mRNA increased significantly (p < 0.05) in smooth
      muscle cells of the rat cervix as a result of increased copy numbers of OTR mRNA
      per cell as well as an increased population of OTR mRNA-positive cells.
      Progesterone alone had no effect on OTR mRNA expression; however, progesterone
      combined with estradiol significantly inhibited the up-regulation of OTR mRNA by
      estradiol alone. The increase of OTR mRNA in cervical epithelial cells was
      minimal in all situations. Intensity of cervical OTR immunostaining in both the
      epithelial cells and cervical smooth muscle cells was also elevated after
      estradiol treatment. The anti-rat OTR antiserum used for immunocytochemistry was
      validated by Western blot analysis. In conclusion, OTR and OTR mRNA were
      localized in smooth muscle cells and in epithelial cells of rat cervix. Estradiol
      dependent activation of OTR gene expression and active OTR synthesis in smooth
      muscle cells account for the increased OTR level in rat cervix in vivo, in which
      progesterone acted as an antagonist of estradiol on OTR gene expression.

PMID- 9780320
TI  - Cellular specificity of interleukin-1beta-stimulated expression of type-2
      prostaglandin H synthase in human amnion cell cultures.
AB  - Interleukin-1beta (IL-1beta) has been shown in numerous studies to increase
      prostaglandin output by cultures of human amnion cells. This is due to an
      increase in the expression of type-2 prostaglandin H synthase (PGHS-2), the
      inducible form of the enzyme, in these cultures. Amnion consists of an epithelial
      layer of cells and a subepithelial mesenchymal layer of cells. The purpose of the
      present study was to determine the cell-type(s) responsible for the IL-1beta
      induced PGHS-2 expression in amnion cultures. Amnion was obtained at term after
      elective Cesarean section or vaginal delivery. Tissues were dispersed with
      collagenase, and cells were plated in multichamber culture slides and cultured
      for 7 days in media supplemented with 10% fetal bovine serum. Cell types were
      characterized with antisera to keratin (epithelial cells) and vimentin
      (mesenchymal cells). Cultures contained both cell types, and the proportion of
      these varied considerably from one culture to another. Cells were treated with
      various concentrations of IL-1beta for 6 or 24 h and were then fixed in 4%
      paraformaldehyde. The fixed cells were permeabilized with Triton and examined by
      immunohistochemistry for PGHS-2 protein using specific antisera, and PGHS-2 mRNA
      was localized by in situ hybridization using a specific oligonucleotide probe.
      The cell type(s) expressing PGHS-2 was characterized using double labeling with
      antisera to keratin (epithelial cell marker) and vimentin (mesenchymal cell
      marker). IL-1beta was found to increase expression of immunoreactive PGHS-2 and
      PGHS-2 mRNA. This increased expression was found to occur only in the vimentin
      positive cells and not the epithelial cells. These results highlight the
      potential importance of the subepithelial cells in the mesenchymal layer of
      amnion in the formation of prostaglandins during pregnancy and possibly in
      preterm labor with infection.

PMID- 9780322
TI  - Effects of long-term testosterone, gonadotropin-releasing hormone agonist, and
      pimozide treatments on gonadotropin II levels and ovarian development in juvenile
      female striped bass (Morone saxatilis).
AB  - The ability of the juvenile female reproductive axis to respond to hormonal
      stimulation was investigated in a Perciform fish, the striped bass (Morone
      saxatilis) using various combinations of testosterone (T), GnRH agonist (GnRHa),
      and pimozide. A long-term treatment with T alone, or T in combination with GnRHa,
      increased pituitary gonadotropin II (GtH II) levels 2- and 3-fold, respectively,
      suggesting that T and GnRHa each stimulate GtH II accumulation. Release of the
      accumulated GtH II could be induced only by high doses of GnRHa in combination
      with T, indicating that GtH II synthesis and release require different levels of
      GnRH stimulation. The addition of the dopamine antagonist pimozide did not affect
      pituitary and plasma GtH II levels but, in response to an additional acute GnRHa
      challenge, inhibited the release of GtH II. Although ovarian development was
      slightly stimulated by a combined T and GnRHa treatment, vitellogenesis was
      generally not initiated. The present study demonstrated that the juvenile striped
      bass pituitary is responsive to hormonal stimulation, resulting in elevated
      levels of GtH II in the pituitary and plasma. However, increased plasma levels of
      GtH II did not result in precocious puberty, suggesting that additional factors
      are required for the initiation of ovarian development in this teleost.

PMID- 9780321
TI  - Mutual and intercompartmental regulation of estrogen receptor and progesterone
      receptor expression in the mouse uterus.
AB  - The epithelial and stromal compartments of the uterus undergo significant
      estrogen- and progesterone (P4)-induced changes during the estrous cycle. While
      in the adult mouse, epithelial proliferation and stromal inflammation are induced
      by estrogen, P4 is antiproliferative in the epithelium and both proliferative and
      anti-inflammatory in the stroma. In light of these compartmentally varying roles,
      we have immunohistochemically examined estrogen and P4 regulation of the
      expression of their receptors (ER and PR) and their epithelial target gene
      lactoferrin (LF) in wild-type and PR null mutant mice. We demonstrate that
      estrogen exerts compartment-specific effects on the expression of ER, resulting
      in decreased levels of stromal and glandular epithelial (GE) ER and increased
      luminal epithelial (LE) and myometrial ER. Estrogen also has dual effects on PR
      expression, decreasing levels in the LE while at the same time increasing levels
      in the stroma and myometrium. Estrogen and P4 together mediate their effects in
      part through the ability of P4 to selectively inhibit myometrial ER expression
      while preserving GE expression. We also demonstrate a general negative feedback
      by P4 on PR expression that is most prominent in the GE. Finally, we demonstrate
      using the estrogen- and P4-responsive epithelial target gene LF that the
      differential regulation of PR in the glandular and luminal epithelium results in
      different functional responses of these compartments to P4. Together, our data
      indicate that the pleiotropic effects of estrogen and P4 in the adult mouse
      uterus are mediated by complex hormonal interregulation of ER and PR in specific
      uterine compartments.

PMID- 9780323
TI  - Age-dependent and lobe-specific spontaneous hyperplasia in the brown Norway rat
      prostate.
AB  - We showed previously that exogenously administered testosterone caused age- and
      lobe-specific overgrowth of the prostate in Brown Norway rats. A common feature
      observed in testosterone-treated animals was cell hypertrophy in each of the
      ventral, dorsal, and lateral lobes of both young (6 mo old) and old (24 mo old)
      rats. By contrast, hyperplasia was seen only in the dorsal and lateral lobes of
      old rats treated with testosterone. These observations prompted us to examine
      whether age- and lobe-specific overgrowth might also occur in untreated rats as a
      consequence of the endogenous hormonal milieu. To this end, blood and prostates
      were collected from a large number (25-30 rats per group) of 4- to 6-mo-old
      (young) and 21- to 24-mo-old (old) Brown Norway rats. Both serum testosterone (
      45%) and estradiol (-22%) concentrations decreased significantly with age, but
      the greater magnitude of the decrement in testosterone relative to estradiol led
      to a reduction in the serum testosterone:estradiol ratio. Paradoxically, although
      the prostate is androgen dependent, the wet weight, protein, and DNA contents
      increased significantly with age in the dorsal and lateral lobes of old rats
      despite the decrease in testosterone level. Histologic examination revealed that
      the increased weights and DNA contents of the dorsal and lateral lobes in old
      rats coincided with an increased number of epithelial cells in the distal and
      intermediate segments of these lobes, indicative of hyperplasia but independent
      of change in cell size. Taken together, these results show a spontaneous age
      related overgrowth of cells in the dorsal and lateral prostatic lobes of old
      Brown Norway rats despite diminished serum testosterone concentrations. The aging
      Brown Norway rat, therefore, may be a useful model for studies of some aspects of
      the pathogenesis underlying spontaneous age-related prostatic hyperplasia.

PMID- 9780324
TI  - Effects of photoperiod and age on secretory patterns of luteinizing hormone and
      testosterone and semen production in male domestic turkeys.
AB  - The objective of this study was to determine effects of photoperiod and age on
      the circulating concentrations of LH, testosterone (T), thyroxine (T4), and semen
      production in male turkeys. Male turkeys from 10 or 12 wk of age were maintained
      under either a long-day (LD) photoperiod of 16L:8D up to 35 wk (LL), or a short
      day (SD) photoperiod of 6L:18D to 29 wk and then an LD photoperiod of 16L:8D up
      to 35 wk of age (SL). Plasma concentrations of both LH and T increased by 17 or
      18 wk of age under both photoperiods, but higher levels were attained in the LL
      group prior to 29 wk of age. Both LH and T levels increased significantly within
      days in the SL group after the group was switched to LD at 29 wk of age. Higher
      levels of T4 were present in the LL group prior to sexual maturation. No
      differences were observed in T4 concentration between lighting treatments after
      sexual maturation. The LL group first produced semen at 20-22 wk of age, which
      was about 1 wk earlier than first semen production in the SL group. A
      significantly larger volume of semen was produced in the LL group at most ages.
      No further increase in semen production was observed in the first 6 wk after the
      SL group was switched to the LD photoperiod at 29 wk of age. Pulsatile patterns
      of LH and T were characterized by serial blood sampling at 13, 23, and 35 wk of
      age under both the LL and SL photoperiods. The baseline levels of both LH and T
      in male turkeys were influenced by age and photoperiod. However, pulse
      characteristics (numbers, duration, and amplitude) of LH did not change with age
      or lighting treatment, while pulse characteristics of T did change with age. We
      conclude that exposing male turkeys to an LD photoperiod from 10 or 12 wk of age
      advanced the age of sexual maturation and induced earlier increased
      concentrations of LH and T.

PMID- 9780325
TI  - A combinatorial phage display library for the generation of specific Fab
      fragments recognizing human spermatozoa and inhibiting fertilizing capacity in
      vitro.
AB  - To select a source of lymphocytes for the generation of an anti-sperm-biased
      combinatorial phage display library, venous blood was obtained from 34
      vasovasostomy (vasectomy reversal) patients approximately 3 mo after surgery.
      Using a variety of immunoassays, serum was analyzed for antibodies against human
      spermatozoa, and a patient was selected on the basis of high titer of antibodies
      that recognized the equatorial region of the sperm head and inhibited sperm
      fertilizing capacity in vitro. Total RNA isolated from the stored lymphocytes of
      this individual was reversed transcribed, and gamma1 (Fd) region and kappa chains
      were amplified by polymerase chain reaction for the successful construction of an
      antibody phage display library. The library was panned against human spermatozoa
      to isolate sperm-specific phage that recognized the equatorial region of the
      sperm head. Three preparations of Fab were tested via the hamster egg penetration
      test. Each preparation significantly (p < 0. 005) inhibited sperm-egg binding and
      fusion, with one preparation (designated Fab-G) causing complete inhibition.
      Sequence analysis of the kappa light gene encoding Fab-G revealed a 93% homology
      with the light chain of human anti-human immunodeficiency virus gp120 p35
      variable region. This technology may have a practical application in
      characterization of the immune response to spermatozoa and for the design of
      sperm-based contraceptive vaccines.

PMID- 9780327
TI  - Gonadotropin response to naloxone in the mare: effect of time of year and
      reproductive status.
AB  - In the mare, endogenous opioids have been implicated in the suppression of
      gonadotropin secretion during seasonal anestrus (AN). The present study tested
      whether continuation of reproductive activity during the nonbreeding season (NBS)
      reflects the absence of a seasonal shift in opioid tone compared to what occurs
      in AN mares. During the NBS, 11 AN and 8 luteal-phase mares received 0.1, 0.05,
      0. 025 mg/kg naloxone (NAL) or vehicle on alternate days. Whereas cycling mares
      responded to all dosages of NAL, AN mares responded only to the higher dosages
      for FSH, and LH failed to increase at any dosage employed. During the breeding
      season (BS), the response to these dosages of NAL was reevaluated in 12 mares in
      the luteal phase of a synchronized estrous cycle. Although there was no
      difference between cycling mares during the breeding and nonbreeding seasons in
      FSH response, those mares that had cycled during the NBS showed a greater LH
      response to 0.05 mg/kg NAL than mares during the BS. From these data, we conclude
      that opioid tone is lower during the BS than during AN and that this shift in
      inhibitory tone does not occur in mares that cycle during the NBS. Thus, reduced
      opioid tone may play a role in the mechanisms controlling the nonseasonal
      exhibition of estrous cycles in the mare.

PMID- 9780326
TI  - In vitro culture of hamster ovarian primary interstitial cells: effect of serum.
AB  - The function of ovarian interstitial cells has been largely addressed using rat
      theca-interstitial cell culture. However, this preparation is primarily enriched
      with theca and secondary interstitial cells, which make it difficult to address
      selectively the function of the primary interstitial cells. We have developed an
      in vitro culture of hamster ovarian primary interstitial cells. Cells were
      isolated from postnatal hamster ovaries by collagenase digestion and purified
      over a Percoll gradient. The preparation contained 90% viable, pure interstitial
      cells, which anchored to the plastic and glass culture surface in the presence of
      fetal bovine serum. Cell proliferation was noted in the presence of serum dosages
      higher than 0.2%; however, reduction of serum concentration to 0.1% or complete
      serum starvation did not affect cell viability but almost completely abolished
      cell proliferation as determined by [3H]thymidine incorporation, labeling index,
      and DNA content of the culture. All cells exhibited active 3beta-hydroxysteroid
      dehydrogenase and P450 side chain cleavage immunoreactivity, which corresponded
      to basal progesterone and androstenedione accumulation. Replacement of serum to
      starving cells resulted in the induction of the "S" phase and "M" phase specific
      cyclins, and resumption of cell proliferation. Our results indicate that hamster
      primary interstitial cells can be cultured in vitro as a monolayer, and the
      anchorage and proliferation of these cells depend on serum supplement; however, a
      viable monolayer can be maintained for several days without serum. This model
      will be useful for addressing the mechanisms of differentiation of ovarian
      interstitial cells.

PMID- 9780328
TI  - Both prolactin and progesterone in proestrus are necessary for the induction of
      apoptosis in the regressing corpus luteum of the rat.
AB  - This study was conducted to analyze the roles of prolactin (PRL) and progesterone
      in the induction of luteal cell apoptosis and accumulation of macrophages in the
      regressing corpus luteum. We studied the number of apoptotic cells and
      macrophages in regressing corpora lutea in estrus 1) in cycling rats or after
      blocking PRL secretion with the dopaminergic agonist CB154, and 2) after blocking
      progesterone actions with the progesterone receptor antagonists RU-486 or
      ZK98299. Cells showing the morphological features characteristic of apoptosis
      contained fragmented DNA as indicated by in situ 3' end labeling. In cycling
      rats, a 100-fold increase in the number of apoptotic cells and a 4-fold increase
      in the number of macrophages was found from the evening (1600 h) of proestrus to
      the morning (1100 h) of estrus. Both increases were blocked by PRL suppression
      with CB154. Furthermore, blocking progesterone actions with progesterone receptor
      antagonists RU-486 or ZK98299 without affecting PRL secretion inhibited apoptosis
      but did not affect the accumulation of macrophages, whether treatment was started
      on the morning of metestrus (blocking diestrous and proestrous progesterone) or
      on proestrus (blocking only proestrous progesterone). Otherwise, exogenous
      progesterone was not effective in inducing apoptosis in the absence of PRL. These
      results indicate that both PRL and progesterone in proestrus are necessary for
      the induction of apoptosis in the regressing corpora lutea, whereas the
      accumulation of macrophages seemed to be dependent exclusively on the PRL surge.

PMID- 9780329
TI  - Localization of connective tissue growth factor during the period of embryo
      implantation in the mouse.
AB  - A role for connective tissue growth factor (CTGF) in reproductive function has
      been suggested from recent studies in the pig. To extend these findings, we have
      analyzed the immunohistochemical localization of CTGF during the estrous cycle
      and early pregnancy in mice. During the diestrous and early proestrous stages,
      CTGF was localized at high levels to both luminal and glandular uterine
      epithelial cells and at much lower levels in the stroma or myometrium. Epithelial
      expression of CTGF was considerably reduced at estrus. On Days 1.5-3.5 of
      pregnancy, CTGF was localized mainly to the uterine epithelial cells, which
      showed a substantially reduced level of CTGF on Day 4.5. On Days 5.5 and 6.5,
      CTGF was present at high levels in uterine decidual cells. CTGF was detected in
      the trophectoderm and inner cell mass of the preimplantation embryo on Day 4.5
      and became preferentially localized to embryonic endoderm and mesoderm on Days
      5.5-6.5. Multiple mass forms of CTGF (Mr 14 000-38 000) were present in
      endometrial extracts and uterine luminal flushings. Collectively, these data
      support a role for CTGF in uterine cell growth, migration, adhesion, and
      extracellular matrix production during the estrous cycle and early pregnancy, as
      well as in early development of the embryo.

PMID- 9780330
TI  - Characterization of domains in mice of calnexin-t, a putative molecular chaperone
      required in sperm fertility, with use of glutathione S-transferase-fusion
      proteins.
AB  - Calnexin-t (calmegin) is a male germ cell-specific variant of calnexin, a
      membrane bound-molecular chaperone in the endoplasmic reticulum (ER). Although it
      is temporally expressed during spermatogenesis, it has recently been shown to be
      highly involved in sperm fertility. To investigate the biochemical states of
      calnexin-t during spermatogenesis, we produced a series of glutathione S
      transferase-fusion proteins with several specific coding domains of calnexin-t.
      Immunostaining and 45Ca2+ overlay assays clearly showed that the internal proline
      rich repeat region has Ca2+-binding ability and contains an epitope recognized by
      monoclonal antibody 1C9. Western blot analysis of protein extracts from the
      testes of 10-, 18-, 26-, and 60-day-old mice revealed only a single 101-kDa
      protein during testicular development by 1C9. Anti-C, a cytoplasmic domain
      specific antibody generated by immunization with recombinant protein, produced
      the same results, indicating that the 101-kDa form of calnexin-t is prevalent at
      all stages of spermatogenesis expressing calnexin-t. In paraffin sections of
      mouse testis, Anti-C stained spermatocytes and spermatids intensely, whereas 1C9
      stained spermatocytes only slightly but spermatids intensely, suggesting that the
      affinity of 1C9 for its epitope is lower in pachytene spermatocytes than in
      spermatids. Acid phosphatase treatment of the 101-kDa form generated a 93-kDa
      band that in turn could be recovered to the 101-kDa form by incubation with HeLa
      cell S100 fraction, indicating that the 101-kDa form is a phosphorylated type of
      calnexin-t. The sites of phosphorylation were shown to be restricted to the
      cytoplasmic domain. Our results suggest that the structure of the ER luminal
      domain of calnexin-t is likely to differ in middle pachytene versus haploid germ
      cell phases. In addition, the cytoplasmic domain of calnexin-t was shown to be
      highly phosphorylated immediately after protein synthesis and constitutively
      phosphorylated during spermatogenesis.

PMID- 9780331
TI  - Role of fibroblast growth factors and their receptors in mouse primordial germ
      cell growth.
AB  - Primordial germ cells (PGCs) are the embryonic progenitors of mature germ cells.
      During their proliferative stage, murine PGCs may be transiently cultured on
      mitotically inactive feeder layers. This culture system has permitted
      identification of several growth factors active toward PGCs. We and others have
      previously identified basic fibroblast growth factor (bFGF) as a powerful mitogen
      in this system. Here we characterize some of the functions of bFGF in PGC
      culture. Our data demonstrate that fibroblast growth factor (FGF) receptors I and
      II are present in the developing gonad and are consistent with expression of
      these receptors by PGCs. Moreover, PGCs can bind radiolabeled bFGF in vitro,
      demonstrating that the factor can act directly on these cells. While mitotic PGCs
      of either sex are shown to bind radiolabeled bFGF, oogonia that are undergoing
      meiotic arrest exhibit reduced bFGF binding, indicating potential developmental
      regulation of an FGF receptor.

PMID- 9780332
TI  - The chicken homologue of zona pellucida protein-3 is synthesized by granulosa
      cells.
AB  - Oocyte development within avian ovarian follicles is an intricate process
      involving yolk deposition and the formation of extraoocytic matrices. Of these,
      the perivitelline membrane (pvm) not only plays a role in sperm binding but also
      provides mechanical support for the large oocyte's journey through the oviduct
      after ovulation. To date we have focused on the mechanisms for uptake of yolk
      precursors into oocytes of the chicken; now we extend our studies to a detailed
      analysis of the pvm. In the course of characterization of its major components,
      we obtained partial protein sequences; comparison with the GenBank database
      revealed that one of the pvm proteins is the homologue of mammalian zona
      pellucida glycoprotein 3 (ZP3), a key component in sperm binding. Following a
      nomenclature based on gene structure, the protein is referred to as chicken ZPC
      (chZPC). The chicken protein (444 residues) and murine ZP3 (424 residues) are
      highly conserved, with 41% of the amino acids identical. As shown by Northern
      blot analysis, the avian ZPC gene is expressed exclusively in the granulosa cells
      surrounding the oocyte, in contrast to murine ZP3, which is synthesized by the
      oocyte. Upon reaching a size larger than 1.5 mm in diameter, follicles accumulate
      chZPC in highly polarized fashion, i.e., in the space intercalated between the
      oocyte and the granulosa cells, as revealed by immunohistochemistry of follicle
      sections. ChZPC synthesis and secretion by granulosa cells was demonstrated
      directly by metabolic labeling and immunoprecipitation from the culture medium of
      granulosa cell sheets isolated ex vivo from follicles. Immunoblot analysis and
      glycosidase treatment of chZPC from preovulatory and freshly ovulated oocytes, as
      well as laid eggs, revealed that the primary product undergoes a two-step
      decrease in size from follicle to laid egg that is unlikely to be due to
      modification of the carbohydrate moiety.

PMID- 9780333
TI  - Characterization of a major permeability barrier in the zebrafish embryo.
AB  - Fish embryos represent a class of multicompartmental biological systems that have
      not been successfully cryopreserved, primarily because of the lack of
      understanding of how water and cryoprotectants permeate the compartments. We are
      using the zebrafish embryo as a model to understand these kinetics. Zebrafish
      embryos have two major compartments, the blastoderm and the yolk, which is
      surrounded by the multinucleated yolk syncytial layer (YSL). We determined the
      water and cryoprotectant permeability in these compartments using two methods.
      First, we measured shrink/swell dynamics in optical volumetric experiments.
      Zebrafish embryos shrank over time and did not re-expand while immersed in
      dimethyl sulfoxide (DMSO) or propylene glycol. Second, we measured DMSO uptake
      with diffusion-weighted nuclear magnetic resonance spectroscopy. DMSO uptake was
      rapid during the first few minutes, then gradual thereafter. We used one- and two
      compartment models to analyze the data and to determine the permeability
      parameters. We found that the two-compartment model provided a better fit to the
      data. On the basis of this model and in the presence of DMSO, the yolk and
      blastoderm had very similar water permeabilities (i.e., 0.01 and 0. 005 micron x
      min-1atm-1, respectively), but they had different DMSO permeabilities separated
      by three orders of magnitude (i.e., </= 5 x 10(-6) and 1.5 x 10(-3) cm/min,
      respectively). The low solute permeability of the yolk predicted that the
      yolk/YSL compartment should be more susceptible to cryodamage. To test this, the
      yolk, blastoderm, and YSL were examined at the ultrastructural level after
      vitrification. Only the YSL incurred significant damage after freezing and
      thawing (p </= 0.05).

PMID- 9780334
TI  - Paracrine inducers of uterine endometrial spermidine/spermine N1
      acetyltransferase gene expression during early pregnancy in the pig.
AB  - The endogenous factors that underlie the transient induction of the gene encoding
      spermidine/spermine N1-acetyltransferase (SSAT), the rate-limiting enzyme in
      cellular polyamine catabolism, in pig uterine endometrium during periimplantation
      are not known. The present study examined a number of peptide growth factors and
      regulatory molecules that are present within the uterine environment at early
      pregnancy, coincident with maximal SSAT gene expression, for their ability to
      manifest endogenous SSAT gene-inducing activity. Basal SSAT expression in luminal
      epithelial cells was higher (p < 0. 01) than that for glandular epithelial (GE)
      or stromal (ST) cells. Recombinant human insulin-like growth factor-I (IGF-I; 50
      ng/ml) had no effect on steady-state SSAT mRNA levels, but it increased
      mitogenesis in all three cell types. In contrast, IGF-I caused a marked induction
      (p < 0.01) of SSAT mRNA levels in the human endometrial carcinoma cell line Hec-1
      A. Uterine explants incubated with interleukin-6, transforming growth factor
      alpha, epidermal growth factor (each at 1, 10, and 100 ng/ml), retinoic acid and
      retinol (each at 0.01, 0.1, and 1 microM), and estradiol-17beta (10 nM) had SSAT
      mRNA levels similar to controls. By contrast, leukemia inhibitory factor (LIF; at
      10 and 100 ng/ml) caused a modest, but significant (p < 0.05), increase in SSAT
      mRNA levels over those of untreated explants. This effect of LIF, however, did
      not approach the level of induction observed in GE or ST cells after addition of
      medium conditioned by Day 12 or 17 porcine conceptuses and in endometrial
      explants supplemented with medium conditioned by Day 21 porcine conceptuses or a
      continuous cell line (Jag-1) derived from Day 14 porcine trophoblast. We suggest
      that transient induction of endometrial SSAT gene expression at implantation is
      mediated by the functional interactions of specific conceptus-derived regulatory
      factors, distinct from estrogen, with endometrial-derived factor(s) such as LIF.
      These complex interactions are probably requisite for the transient, yet
      dramatic, induction of SSAT gene expression and may be critical for successful
      implantation.

PMID- 9780335
TI  - Oxytocin-stimulated phosphoinositide hydrolysis and prostaglandin F secretion by
      luminal epithelial, glandular epithelial, and stromal cells from pig endometrium.
      I. Response of cyclic pigs on day 16 postestrus.
AB  - Oxytocin (OT) is the physiological stimulus for pulsatile release of endometrial
      prostaglandin (PG) F2alpha during luteolysis in domestic ungulates, and the
      cellular mechanism for this appears to involve phosphoinositide (PI) hydrolysis.
      To determine which endometrial cell type(s) was responsive to OT during
      luteolysis in swine, luminal epithelial (LEC), glandular epithelial (GEC), and
      stromal cells (SC) were isolated from endometrium by differential enzymatic
      digestion and sieve filtration on Day 16 postestrus and cultured. For PI
      hydrolysis in experiment 1, SC were most responsive to 100 nM OT (p < 0.001),
      whereas LEC were least responsive and GEC had an intermediate response (p <
      0.001). For PGF secretion in experiment 2, the response to OT was greatest for
      SC, least for LEC, and intermediate for GEC. In experiment 3, 100 nM OT increased
      PI hydrolysis in SC within 30 min (p < 0.05) and in GEC within 60 min (p < 0.05)
      but did not increase PI hydrolysis in LEC. In experiment 4, PI hydrolysis in SC
      was increased (p < 0.05) by 33-333 nM OT but was not increased by </= 333 nM OT
      in GEC or LEC after 30 min. However, PGF secretion from SC was increased (p <
      0.05) by 10-333 nM OT, and from GEC by 10-333 nM OT, but was not increased from
      LEC by </= 333 nM OT. Results of this study indicate that 1) there was
      differential responsiveness to OT among endometrial cell types, and 2) within
      cell type, there generally was a similar response to OT for both PI hydrolysis
      and PGF secretion, further implicating PI hydrolysis as the signaling pathway for
      OT-stimulated PGF2alpha release. The differential response of endometrial cell
      types may have an important role in the pattern of PGF2alpha secretion during
      luteolysis in swine.

PMID- 9780336
TI  - Mammalian male and female germ cells express a germ cell-specific Y-Box protein,
      MSY2.
AB  - Here we report the isolation and characterization of mouse testicular cDNAs
      encoding the mammalian homologue of the Xenopus germ cell-specific nucleic acid
      binding protein FRGY2 (mRNP3+4), hereafter designated MSY2. MSY2 is a member of
      the Y box multigene family of proteins; it contains the cold shock domain that is
      highly conserved among all Y box proteins and four basic/aromatic islands that
      are closely related to the other known germline Y box proteins from Xenopus,
      FRGY2, and goldfish, GFYP2. Msy2 undergoes alternative splicing to yield
      alternate N-terminal regions upstream of the cold shock domain. Although MSY2 is
      a member of a large family of nucleic acid-binding proteins, Southern blotting
      detects only a limited number of genomic DNA fragments, suggesting that Msy2 is a
      single copy gene. By Northern blotting and immunoblotting, MSY2 appears to be a
      germ cell-specific protein in the testis. Analysis of Msy2 mRNA expression in
      prepubertal and adult mouse testes, and in isolated populations of germ cells,
      reveals maximal expression in postmeiotic round spermatids, a cell type with
      abundant amounts of stored messenger ribonucleoproteins. In the ovary, MSY2 is
      present exclusively in diplotene-stage and mature oocytes. MSY2 is maternally
      inherited in the one-cell-stage embryo but is not detected in the late two-cell
      stage embryo. This loss of MSY2 is coincident with the bulk degradation of
      maternal mRNAs in the two-cell embryo.

PMID- 9780337
TI  - Effect of matching of class I HLA alleles on clinical outcome after
      transplantation of hematopoietic stem cells from an unrelated donor. Japan Marrow
      Donor Program.
AB  - BACKGROUND: The requirements with respect to HLA compatibility and the relative
      importance of matching for individual class I and class II HLA alleles in the
      transplantation of hematopoietic stem cells from unrelated donors have not yet
      been established. METHODS: We performed retrospective DNA typing of alleles at 11
      polymorphic loci of HLA genes in 440 recipients of hematopoietic stem cells from
      unrelated donors who were serologically identical with their respective
      recipients for HLA-A, B, and DR antigens. Of these recipients, 80 percent had
      leukemia; the rest had lymphoma, marrow failure, or a congenital disorder.
      RESULTS: Multivariate analysis showed that incompatibility for HLA-A alleles and
      incompatibility for HLA-C alleles were independent risk factors for severe acute
      graft-versus-host disease (GVHD) (HLA-A, P=0.006; HLA-C, P=0.001). Mismatching of
      HLA-A, but not of HLA-C, alleles was an independent risk factor for death
      (P<0.001). Matching [corrected] of HLA-C alleles was a significant risk factor
      for relapse of leukemia (P=0.035). HLA-B disparity was a significant risk factor
      for both GVHD and death in the univariate analysis, but not in multivariate
      analysis. Disparities in class II HLA alleles of the DRB1, DQA1, DQB1, DPA1, and
      DPB1 loci were not identified as significant risk factors for acute GVHD or death
      in the multivariate analysis. CONCLUSIONS: Genomic typing of class I HLA alleles
      adds substantially to the success of transplantation of hematopoietic stem cells
      from unrelated donors, even if the donors are serologically identical to their
      recipients with respect to HLA-A, B, and DR antigens.

PMID- 9780338
TI  - Treatment of high-risk acute leukemia with T-cell-depleted stem cells from
      related donors with one fully mismatched HLA haplotype.
AB  - BACKGROUND: In this study we tried to achieve successful transplantation in
      patients with acute leukemia with the use of hematopoietic stem cells from donors
      who shared only one HLA haplotype with the recipient (a "full-haplotype
      mismatch"). To prevent graft failure, large doses of T-cell-depleted
      hematopoietic stem cells were transplanted after a conditioning regimen of
      enhanced myeloablation and immunosuppression was administered to the recipient.
      METHODS: Forty-three patients with high-risk acute leukemia who were scheduled
      for transplantation received total-body irradiation, thiotepa, fludarabine, and
      antithymocyte globulin. The graft consisted of peripheral-blood progenitor cells
      that had been mobilized in the donor with recombinant granulocyte colony
      stimulating factor and also, in 28 cases, bone marrow. Bone marrow from the donor
      was depleted of T lymphocytes by processing with soybean agglutinin and E
      rosetting. T-cell depletion of peripheral-blood mononuclear cells was achieved by
      E-rosetting followed by positive selection of CD34+ cells. No post
      transplantation prophylaxis against graft-versus-host disease (GVHD) was
      administered. RESULTS: In all the patients, full donor-type engraftment was
      achieved. In none of the patients who could be evaluated did acute or chronic
      GVHD develop. Regimen-related toxicity was minimal. Eleven of the 23 patients
      with acute lymphoblastic leukemia had a relapse, as did 2 of the 20 patients with
      acute myeloid leukemia. Transplantation-related mortality was 40 percent. After a
      median follow-up of 18 months (range, 8 to 30), 12 of the 43 patients were alive
      and free of disease. All surviving patients had a good quality of life.
      CONCLUSIONS: The main limitations of transplantation of bone marrow from donors
      who are matched with the recipient for only one HLA haplotype GVHD and graft
      failure - can be overcome. Since most patients have a relative with one haplotype
      mismatch, advances in this method will increase the availability of hematopoietic
      cell transplantation as curative therapy for acute leukemia.

PMID- 9780339
TI  - A 15-year follow-up study of ventilatory function in adults with asthma.
AB  - BACKGROUND: Although the prevalence of asthma and morbidity related to asthma are
      increasing, little is known about the natural history of lung function in adults
      with this disease. METHODS: We used data from a longitudinal epidemiologic study
      of the general population in a Danish city, the Copenhagen City Heart Study, to
      analyze changes over time in the forced expiratory volume in one second (FEV1) in
      adults with self-reported asthma and adults without asthma. The study was
      conducted between 1976 and 1994; for each patient, three measurements of lung
      function were obtained over a 15-year period. The final data set consisted of
      measurements from 17,506 subjects (8136 men and 9370 women), of whom 1095 had
      asthma. RESULTS: Among subjects who participated in all three evaluations, the
      unadjusted decline in FEV1 among subjects with asthma was 38 ml per year, as
      compared with 22 ml per year in those without asthma. The decline in FEV1
      normalized for height (FEV1 divided by the square of the height in meters) was
      greater among the subjects with asthma than among those without the disease
      (P<0.001). Among both men and women, and among both smokers and nonsmokers,
      subjects with asthma had greater declines in FEV1 over time than those without
      asthma (P<0.001). At the age of 60 years, a 175-cm-tall nonsmoking man without
      asthma had an average FEV1 of 3.05 liters, as compared with 1.99 liters for a man
      of similar age and height who smoked and had asthma. CONCLUSIONS: In a sample of
      the general population, people who identified themselves as having asthma had
      substantially greater declines in FEV1 over time than those who did not.

PMID- 9780340
TI  - Myocardial bridging in children with hypertrophic cardiomyopathy--a risk factor
      for sudden death.
AB  - BACKGROUND: Myocardial bridging may cause compression of a coronary artery, and
      it has been suggested that myocardial ischemia may result. The clinical
      significance and prognostic value of myocardial bridging of the left anterior
      descending coronary artery in children with hypertrophic cardiomyopathy are
      unknown. We sought to determine the prevalence and clinical effects of myocardial
      bridging in children with hypertrophic cardiomyopathy who underwent cardiac
      catheterization. METHODS: Angiograms from 36 children with hypertrophic
      cardiomyopathy were reviewed to determine whether myocardial bridging was present
      and, if so, to assess the characteristics of systolic narrowing of the left
      anterior descending coronary artery caused by myocardial bridging and the
      duration of residual diastolic compression. We also reviewed clinical data on
      these patients. RESULTS: Myocardial bridging was present in 10 (28 percent) of
      the patients. Compression of the left anterior descending coronary artery
      persisted for a mean (+/-SD) of 50+/-17 percent of diastole. As compared with
      patients without bridging, patients with bridging had a greater incidence of
      chest pain (60 percent vs. 19 percent, P=0.04), cardiac arrest with subsequent
      resuscitation (50 percent vs. 4 percent, P=0.004), and ventricular tachycardia
      (80 percent vs. 8 percent, P<0.001). On average, the patients with bridging had a
      reduction in systolic blood pressure with exercise of 17+/-27 mm Hg, as compared
      with an elevation of 43+/-31 mm Hg in those without bridging (P<0.001). The
      patients with bridging also had greater ST-segment depression with exercise
      (median, 5 vs. 0 mm, P=0.004) and a shorter duration of exercise (mean, 6.6+/-2.4
      vs. 9.1+/-1.4 minutes, P=0.008). The degree of dispersion of the QT interval
      corrected for heart rate on the electrocardiogram was greater in patients with
      bridging than in those without bridging (104+/-46 vs. 48+/-31 msec, P=0.002).
      Kaplan-Meier estimates of the proportions of patients who had not died or had
      cardiac arrest with subsequent resuscitation five years after the diagnosis of
      hypertrophic cardiomyopathy were 67 percent among patients with bridging and 94
      percent among those without bridging (P=0.004). CONCLUSIONS: Myocardial bridging
      is associated with a poor outcome in children with hypertrophic cardiomyopathy.
      Our observations suggest that bridging is associated with myocardial ischemia

PMID- 9780341
TI  - Images in clinical medicine. Biliary sludge extruding into the duodenum.

PMID- 9780342
TI  - Risk factors for infant homicide in the United States.
AB  - BACKGROUND: Homicide is the leading cause of infant deaths due to injury. More
      than 80 percent of infant homicides are considered to be fatal child abuse. This
      study assessed the timing of deaths and risk factors for infant homicide.
      METHODS: Using linked birth and death certificates for all births in the U.S.
      between 1983 and 1991, we identified 2776 homicides occurring during the first
      year of life. Birth-certificate variables were reviewed in both bivariate and
      multivariate stratified analyses. Variables potentially predictive of homicide
      were selected on the basis of increased relative risks among subcategories with
      adequate numbers for stable estimates. RESULTS: Half the homicides occurred by
      the fourth month of life. The most important risk factors were a second or
      subsequent infant born to a mother less than 17 years old (relative risk, 10.9)
      or 17 to 19 years old (relative risk, 9.3), as compared with a first infant born
      to a mother 25 years old or older; a maternal age of less than 15 years, as
      compared with an age of at least 25 years (relative risk, 6.8); no prenatal care
      as compared with early prenatal care (relative risk, 10.4); and less than 12
      years of education among mothers who were at least 17 years old (relative risk,
      8.0), as compared with 16 or more years of education. CONCLUSIONS: Childbearing
      at an early age was strongly associated with infant homicide, particularly if the
      mother had given birth previously. Our findings may have implications for
      prevention.

PMID- 9780343
TI  - Molecular pathogenesis of cholestasis.

PMID- 9780345
TI  - The quest for a bone marrow donor--optimal or maximal HLA matching?

PMID- 9780346
TI  - Infanticide.

PMID- 9780347
TI  - Correction: The Treatment of Croup with Glucocorticoids.

PMID- 9780348
TI  - Protecting patients from discrimination--the Americans with Disabilities Act and
      HIV infection.

PMID- 9780349
TI  - Glycoproteins now and then: a personal account.
AB  - The present article opens with a brief summary of the current knowledge of
      glycoproteins and their medical applications, as compared to the almost complete
      ignorance of these substances during the first half of the century. The author
      then relates how he became interested in carbohydrates in the 1950s, and
      subsequently in glycoproteins. He focuses on the identification of soybean
      agglutinin as the first known plant protein of this class, to which a widely
      occurring N-linked oligomannoside is attached, and continues with an account of
      his work on the coral tree lectin that contains plant-specific N-glycans. Moving
      at the same time deep into lectin research, he describes the discovery of the
      crucial role of bacterial surface lectins in the initiation of infectious
      diseases, thus providing the rationale for the current attempts to use
      carbohydrates for antiadhesion therapy of such diseases. The article ends with a
      survey of the author's contribution to spreading wide the knowledge of
      glycoproteins and of their great importance in biology and medicine.

PMID- 9780350
TI  - Strategies for glycoconjugate analysis.
AB  - Glycoconjugates such as glycoproteins and glycosphingolipids exhibit multiple
      functions in biological systems. A correlation of functional features with
      defined structural parameters, however, presupposes detailed information on the
      glycoconjugates' carbohydrate moieties including the type of linkage of the
      oligosaccharide chain(s), monosaccharide composition as well as sequence, linkage
      positions and anomeric configurations of individual sugar monomers. Chemical and
      biochemical analyses are often impeded by the limited amounts of sample available
      and the vast structural heterogeneity of glycoconjugate glycans, thus requiring
      highly sensitive and efficient methods for detection, separation and structural
      elucidation of these carbohydrates. The aim of the article is to present suitable
      strategies for structural characterization of glycoconjugate glycans and to
      briefly review some of the techniques commonly used in this field.

PMID- 9780351
TI  - Glycoproteins and their relationship to human disease.
AB  - Glycoproteins are proteins that carry N- and O-glycosidically-linked carbohydrate
      chains of complex structures and functions. N-glycan chains are assembled in the
      endoplasmic reticulum and the Golgi by a controlled sequence of
      glycosyltransferase and glycosidase processing reactions involving dolichol
      intermediates. The assembly of O-glycans occurs in the Golgi and does not involve
      dolichol. For most reactions, families of glycosyltransferases exist; the
      expression of the individual enzymes within a family is often subject to complex
      regulation. The biosynthesis of N- and O-glycan is controlled at the level of
      gene expression, mRNA, enzyme protein activity and localization, and through
      substrate and cofactor concentrations at the site of synthesis. This complex
      regulation results in many hundreds of structures, the range of which varies in
      different species, cell types, tissue types, states of development and
      differentiation. In diseased cells, the relative proportions of these structures
      are often characteristically different from normal, and may be useful for the
      assessment of the stage of the disease and for diagnosis. Knowledge of disease
      specific glycoprotein structures and their functions may be used therapeutically,
      in immunotherapy, in blocking cell adhesion or interfering with other binding or
      biological processes. Recently, some of the mechanisms underlying glycoprotein
      alterations in disease have been elucidated. This opens the possibility of an
      active interference in the disease process. The functions of glycans in diseased
      cells will become more clear with the tools of molecular biology and transgenic
      animal models.

PMID- 9780352
TI  - Cancer-associated glycosphingolipid antigens: their structure, organization, and
      function.
AB  - Experimental and human cancers are often characterized by the presence of tumor
      associated glycosphingolipid (GSL) antigens defined by monoclonal antibodies.
      Major progress has been made during the past two decades on structural
      identification of these antigens. None of these structures are truly 'tumor
      specific'. However, many of the antibodies show preferential or 'specific'
      reactivity with tumors, based on organizational differences of membrane GSLs in
      tumor cells versus normal cells. Clustered GSL antigens organized with transducer
      molecules in microdomain have been found recently to comprise a structural and
      functional unit involved in tumor cell adhesion coupled with signal transduction.
      Some of the GSL antigens have been identified as adhesion molecules recognized by
      carbohydrate-binding proteins or by complementary carbohydrates on target cells.
      Such adhesion, coupled with signaling, may initiate the metastatic process.
      Elucidating the mechanism of this initial adhesion/signaling step may lead to
      discovery of therapeutic agents that disrupt adhesion ('antiadhesion therapy') or
      normalize signaling ('ortho-signaling therapy'). Tumor-associated GSL antigens
      are also a target in immunotherapy of tumors, including development of antitumor
      vaccines.

PMID- 9780353
TI  - Lectin ligands: new insights into their conformations and their dynamic behavior
      and the discovery of conformer selection by lectins.
AB  - The mysteries of the functions of complex glycoconjugates have enthralled
      scientists over decades. Theoretical considerations have ascribed an enormous
      capacity to store information to oligosaccharides. In the interplay with lectins
      sugar-code words of complex carbohydrate structures can be deciphered. To
      capitalize on knowledge about this type of molecular recognition for rational
      marker/drug design, the intimate details of the recognition process must be
      delineated. To this aim the required approach is garnered from several fields,
      profiting from advances primarily in X-ray crystallography, nuclear magnetic
      resonance spectroscopy and computational calculations encompassing molecular
      mechanics, molecular dynamics and homology modeling. Collectively considered, the
      results force us to jettison the preconception of a rigid ligand structure. On
      the contrary, a carbohydrate ligand may move rather freely between two or even
      more low-energy positions, affording the basis for conformer selection by a
      lectin. By an exemplary illustration of the interdisciplinary approach including
      up-to-date refinements in carbohydrate modeling it is underscored why this
      combination is considered to show promise of fostering innovative strategies in
      rational marker/drug design.

PMID- 9780354
TI  - Signaling pathways for transduction of the initial message of the glycocode into
      cellular responses.
AB  - The sugar units of glycan structures store information and establish an alphabet
      of life. The language of the oligosaccharide coding units is deciphered by
      receptors such as lectins and the decoded message can be transduced by multiple
      signaling pathways. Similar to glycoconjugates, these receptors can exhibit
      pronounced changes in quantitative and qualitative aspects of expression, as
      attested by a wealth of lectin and immunohistochemical studies. Since
      histochemistry provides a static picture, it is essential to shed light on the
      mechanisms of how a recognitive protein-carbohydrate interplay can be transduced
      into cellular responses. Their consequences for example for cell morphology will
      then be visible to the histochemist. Therefore, basic signaling routes will be
      graphically outlined and their trigger potential will be explained by selected
      examples from the realm of glycosciences.

PMID- 9780355
TI  - Plant lectins - more than just tools for glycoscientists: occurrence, structure,
      and possible functions of plant lectins.
AB  - Plant lectins are easily available, fairly stable and suitable for many kinds of
      chemical modification. Thus, they have become important tools in glycosciences.
      In the present review, it is attempted to throw light upon aspects of lectinology
      that deal with their natural occurrence, biosynthesis, structure, binding
      specificities and hypotheses about their biological functions.

PMID- 9780356
TI  - Glycocoding as an information management system in embryonic development.
AB  - The past 5 years have seen a burgeoning in the amount of data emerging from
      laboratories studying the early stages of embryogenesis. Much of this data
      implicates various aspects of glycobiology in the initiation and regulation of
      these processes. The level of analytical detail coming from these investigations
      has surpassed our ability to fully understand its overall significance within the
      context of the interactive/dynamic developmental process. This review proposes a
      pause in this seemingly endless quest for more detail so that we may take stock
      of our goals and objectives. The proposed goals include a mechanistic
      understanding of the process(es) involved in information managed at various
      'transition points' during early embryogenesis, and an understanding of the
      mechanism(s) by which the spatial/temporal regulation of early development are
      managed. The 'transitions' which occur during cell to cell cluster, cell cluster
      to early organ architecture, and early organ architecture to functional organ
      development are fundamental and mirror the evolutionary process of biological
      information management. All of these 'transitions' involve increasing complexity,
      the development of hierarchies of information management systems (integrated
      bidirectionally), and spatial/temporal regulation which relies on historical
      events to map future structure and function. This review focuses on a relatively
      small number of studies which highlight these aspects of early development. A
      mechanism which involves glycocoding, an extension of the Roseman Hypothesis, and
      its direct use as an information management system is proposed and some
      supporting experimental evidence is presented. This extension of an existing
      hypothesis is related to several recent investigations, and is designed to
      broaden the experimental design of future studies so that these important process
      issues can be addressed.

PMID- 9780357
TI  - Animal lectins as cell adhesion molecules.
AB  - Protein-carbohydrate interaction is exploited in cell adhesion mechanisms besides
      the recognition of peptide motifs. The sugar code thus significantly contributes
      to the intriguing specificity of cellular selection of binding partners. Focusing
      on two classes of lectins (selectins and galectins), it is evident that their
      functionality for mediation of adhesive contacts is becoming increasingly
      appreciated, as is the integration of this type of interaction with other
      recognition modes to yield the noted specificity. The initial contact formation
      between leukocytes and activated endothelium makes use of selectins to guide
      lymphocyte trafficking. In addition to the three selectins which bind a distinct
      array of ligands, galectin-1 and galectin-3 and possibly other members of this
      family are involved in cell-cell or cell-matrix interactions. This review
      summarizes structural and functional aspects of these two classes of endogenous
      lectins relevant for cell adhesion.

PMID- 9780358
TI  - Structure and functions of lectins in the central and peripheral nervous system.
AB  - There is increasing evidence that lectins are widely distributed in mammalian
      tissues, including the nervous tissue. Based on histochemical techniques using
      neoglycoproteins, different lectin activities specific for different
      monosaccharides or glycans have been identified (fucose, galactose, mannose, N
      acetylglucosamine, N-acetylgalactosamine, N-acetylneuraminic acid and heparin).
      Most of them showed a cellular specificity and developmental regulation in the
      central nervous system. Several lectins isolated from the nervous tissue seem to
      play an essential role during ontogenetic processes, especially as far as cell
      adhesion and cell recognition mechanisms are concerned (axonal growth and
      fasciculation, neuron migration, synaptogenesis, myelination). But some of them
      seem to be involved in signaling events both intracellularly (nuclear lectins) or
      at the cell surface by autocrine and paracrine mechanisms. This review discusses
      the structure and the identified functions of these important constituents of the
      nervous tissue.

PMID- 9780359
TI  - Protein-carbohydrate interactions during fertilization.
AB  - Interaction between gametes during fertilization is at least in part regulated by
      carbohydrate moieties of the zona pellucida (ZP) and carbohydrate binding
      proteins of the sperm surface. This review focuses on the protein-carbohydrate
      interactions during the primary binding of the sperm to the ZP in different
      species. Synthesis, structure and composition of the ZP are summarized. The
      functional significance of carbohydrate residues of the ZP as sperm receptor is
      discussed. Sperm surface proteins known to have specific ZP and carbohydrate
      binding sites including the mouse beta1, 4-galactosyltransferase and sp56, the
      rabbit protein Sp17, a human mannose-binding protein and several members of the
      spermadhesin family are presented.

PMID- 9780361
TI  - Detection of inflammation- and neoplasia-associated alterations in human large
      intestine using plant/invertebrate lectins, galectin-1 and neoglycoproteins.
AB  - Commonly, plant and invertebrate lectins are accepted glycohistochemical tools
      for the analysis of normal and altered structures of glycans in histology and
      pathology. Mammalian lectins and neoglycoproteins are recent additions to this
      panel for the detection of lectin-reactive carbohydrate epitopes and glycoligand
      binding sites. The binding profiles of these three types of probes were
      comparatively analyzed in normal, inflamed and neoplastic large intestine. In
      normal colonic mucosa the intracellular distribution of glycoconjugates and
      carbohydrate ligand-binding sites in enterocytes reveals a differential binding
      of lectins with different specificity and of neoglycoproteins to the Golgi
      apparatus, the rough and smooth endoplasmic reticulum and the apical cell
      surface. The accessible glycoligand-binding sites and the lectin-reactive
      carbohydrate epitopes detected by galectin-1 show the same pattern of
      intracellular location excluding the apical cell surface. Lectin-reactive
      carbohydrate epitopes detected by plant lectins of identical monosaccharide
      specificity as the endogenous lectin [Ricinus communis agglutinin-I (RCA-I),
      Viscum album agglutinin (VAA)], however, clearly differ with respect to their
      intracellular distribution. Maturation-associated differences and heterogeneity
      in glycohistochemical properties of epithelial cells and non-epithelial cells
      (macrophages, dendritic cells, lymphocytes) are found. Dissimilarities in the
      fine structural ligand recognition of lectins with nominal specificity to the
      same monosaccharide have been demonstrated for the galactoside-specific lectins
      RCA-I, VAA and galectin-1 as well as the N-acetylgalactosamine (GalNAc)-specific
      lectins Dolichos biflorus agglutinin (DBA), soybean agglutinin (SBA) and Helix
      pomatia agglutinin in normal mucosa and in acute appendicitis. Acute inflammation
      of the intestinal mucosa found in acute phlegmonous appendicitis is associated
      with selective changes of glycosylation of mucin in goblet cells mainly of lower
      and middle crypt segments resulting in an increase of DBA- and SBA-binding sites
      in the goblet cell population. Appendicitis causes no detectable alteration of
      neoglycoprotein binding. In contrast, tumorigenesis of colonic adenoma is
      characterized by increases in lectin-reactive galactose (Gal; Gal-beta1, 3
      GalNAc), fucose and N-acetylglucosamine moieties and by enhanced presentation of
      respective carbohydrate ligand-binding capacity. This work reveals that
      endogenous lectins and neoglycoproteins are valuable glycohistochemical tools
      supplementing the well-known analytic capacities of plant lectins in the fields
      of gastrointestinal anatomy and gastroenteropathology.

PMID- 9780360
TI  - Applications of lectins and neoglycoconjugates in histology and pathology.
AB  - The biological importance of oligosaccharide sequences in many different settings
      is undeniable. Glycan histochemistry has brought together the histological and
      biochemical approaches and provided insight into the mutual importance of both
      approaches. The aim of the authors is to take a look at a number of ways in which
      modern glycohistochemistry contributes to acquiring knowledge about the key role
      played by carbohydrates in the physiology of vertebrate tissues and human
      disease. The versatility of lectin and neoglycoconjugate histochemical procedures
      is emphasized.

PMID- 9780362
TI  - Glycobiology of the olfactory system.
AB  - The olfactory system is a highly plastic region of the nervous system. Continuous
      remodeling of neuronal circuits in the olfactory bulb takes place throughout life
      as a result of constant turnover of primary sensory olfactory neurons in the
      periphery. Glycoconjugates are very important in olfactory development,
      regeneration and function. This article deals with different aspects of
      glycobiology relevant for the olfactory system. Various anatomical, developmental
      and functional subdivisions of the olfactory system have been labeled with
      exogenous lectins. The application of reverse lectin histochemistry resulted in
      the visualization of endogenous lectins, involved in fasciculation of olfactory
      axons. Numerous glycoproteins, among them members of the immunoglobulin
      superfamily, the cadherins and integrins as well as different glycolipids and
      proteoglycans can act as surface adhesion molecules in the olfactory system. The
      olfactory-specific form of the sialoglycoprotein neural cell adhesion molecule is
      implicated in olfactory neuronal and axonal guidance. Glycoconjugates including
      laminin, fibronectin and proteoglycans are abundant components of the olfactory
      extracellular matrix, influencing neurite outgrowth and cellular migration.
      Immunohistochemical labeling has revealed occurrence of the carbohydrate
      differentiation antigen, playing a role in neurulation and morphogenesis of the
      very early olfactory system. The synaptic vesicle glycoprotein, appearing also
      early in olfactory development, is used as a marker of olfactory tumors. Finally,
      membrane and transmembrane glycoconjugates as well as secreted glycoconjugates
      may act as olfactory receptor molecules.

PMID- 9780363
TI  - Glycoconjugate expression and cartilage development of the cranial skeleton.
AB  - Only few detailed investigations have focused on the glycobiology of cranial
      development. The functional elements in most inductive and morphogenetic
      processes are not individual cells, but rather collectives of interacting
      populations and extracellular matrix components that give rise to specific
      tissues and organs. Experimental evidence strongly suggests that sugar chains not
      only confer morphological characteristics. Complex carbohydrate molecules and
      their corresponding receptors are involved in recognition processes decoding
      biological information during cranial morphogenesis. The distribution patterns of
      glycoconjugates are highly dynamic and show a clear correlation with
      characteristic structural modifications. However, due to the intricate
      interactions in vivo the definitive physiological impact of these observations
      has to be established in further studies. In this review, the spatial and
      temporal patterns of lectin-reactive epitopes and selected receptor types are
      presented and discussed with regard to their potential importance to
      physiological craniogenesis.

PMID- 9780395
TI  - Changing patterns of attempted suicide in Greece: clinicoepidemiological and
      psychodynamic data.
AB  - Greece is known to have one of the lowest rates of both completed and attempted
      suicides. Yet during the last three decades the pattern of suicide attempts has
      shown some differentiations, which point to possible changes in family structure
      and social behavior, bringing the pattern closer to that of western countries.
      While in 1971-72 the ratio of male to female attempters was 1:4.6, in 1994-96 it
      was 1:2.3 - the mean age rose from early to middle adulthood - more married
      people attempted suicide than before - more attempters took alcohol before the
      act etc. There are, nevertheless, many steady features, e.g. the low rates of
      attempters in old age (above 65 years: 7.9% of the total), the methods used, the
      type of preceding stressful life events (more financial than emotional in males),
      no drug abuse etc. Since the low rates of suicide attempts in Greece have been
      attributed to cultural parameters and the close bonds in the family,
      psychodynamic studies were also carried out, which showed that adolescent
      attempters preserve the ability for outward aggression and their self-destructive
      act is due to other than intrapsychic factors (usually social and relational
      problems).

PMID- 9780397
TI  - Gender differences and age of onset in the catatonic subtypes of schizophrenia.
AB  - In a family study involving 139 probands with chronic DSM-III-R schizophrenia,
      catatonic type, 83 probands met the criteria for periodic catatonia and 56
      probands those for systematic catatonia according to Leonhard. In the systematic
      catatonias, we found a low morbidity risk of 4.6% in first-degree relatives, an
      early age at first hospitalization and a high prevalence of affected males. In
      the light of our recent report of an association between maternal gestational
      infection and systematic schizophrenia, male fetuses exposed to midgestational
      infection seem to be particularly at risk of developing systematic catatonia.
      Periodic catatonia with a family morbidity risk of 26.9% affected both genders
      with equal frequency and showed no age-at-onset differences between the genders.
      We found a moderate inverse relationship between early-onset probands and an
      increased risk in relatives of 24.1% compared to 17.8% in late-onset probands.
      Our findings substantiate the hypothesis that periodic catatonia is a clinically
      homogenous disorder with a major gene effect and an age at onset which is to a
      large extent genetically determined.

PMID- 9780396
TI  - Clinical correlates of major depression in Cushing's disease.
AB  - Major depression is a common, life-threatening complication of Cushing's
      syndrome, with no significant differences between pituitary-dependent and 
      independent forms. Little is known about the clinical correlates of depression;
      in particular, whether patients with Cushing's disease and major depression show
      some clinical features that are distinctive compared to those who are not
      depressed. The occurrence of major depression according to DSM-IV criteria was
      ascertained in 162 patients with pituitary-dependent Cushing disease. Major
      depression occurred in 88 of the patients (54%). It was significantly associated
      with older age, female sex, higher pretreatment urinary cortisol levels,
      relatively more severe clinical condition, and absence of pituitary adenoma.
      Patients with Cushing's disease and depression appeared to suffer from a more
      severe form of illness, both in terms of cortisol production and clinical
      presentation, compared to those who were not depressed. Because of these
      connections, the presence of depression is an important clinical feature that
      should not be neglected. The findings in this study may have implications for a
      better understanding of the pathophysiological role of depression associated with
      medical illness.

PMID- 9780398
TI  - What is meant by "misidentification" in delusional misidentification syndromes?
      Comparison between Capgras' syndromes and "clonal pluralization of a person'.
AB  - The semantic structure of Capgras' syndrome (CS) was analyzed within the
      framework of "the theory of reference" of analytic philosophy to elucidate the
      concept of misidentification in delusional misidentification syndromes (DMS). The
      close relationship between the semantic structure of CS and the ordinary use of a
      proper name, which is not synonymous with the description but has the function of
      indicating an object rigidly, is shown. CS is redefined from this perspective,
      and a novel misidentification symptom, which we call "clonal pluralization of a
      person", is contrasted to CS. Among so-called DMS, there are at least two types
      of misidentification with different semantic structures.

PMID- 9780399
TI  - The hysterical personality disorder: a phenomenological approach.
AB  - The background of the present study is a general uncertainty as to what comprises
      the essence of hysterical (histrionic) personality disorder. Using
      phenomenological methodology, phenomena observable in the 'classic' hysterical
      personality are analysed, described, named, and classified according to the basic
      functions of human experience and behaviour. The resulting psychopathological
      picture of the hysterical personality facilitates a differential diagnosis that
      is often decidedly difficult. The phenomenon of dissociation of the mental
      processes is demonstrated for the various basic functions. A specific feature of
      the disorder is shown which generates a dissociation of contents of the
      personality along a conscious-preconscious-unconscious continuum. It is concluded
      that dissocation is, in the final analysis, the prerequisite for a compromised
      and partial acting out of prohibited non-integrated elements, e.g. aggression, as
      a coping strategy.

PMID- 9780400
TI  - Stereotactic surgery--the past and the future.

PMID- 9780401
TI  - Stereotactic treatment of central pain.
AB  - In the present study, the effect of stereotactic treatment on central pain is
      briefly reviewed. Studies have shown that the spinothalamic tract projects to the
      shell zone of the principal sensory nucleus (Vc) and its rostral part (Vim),
      where it forms clusters. Recent anatomophysiological studies have revealed
      specific nociceptive neurons in the thalamic submedius and VMpo nucleus, from
      which fibers project to the insular and cingulate cortex. In the abnormal state
      of central pain, these structures may be subjected to excess excitation. Thalamic
      recording during the course of stereotactic thalamotomy strongly supports this
      hypothesis. Thus, Vim-Vcpc thalamotomy ameliorates the so-called deep pain after
      stroke.

PMID- 9780402
TI  - Pain 

PMID- 9780403
TI  - Surgical management of intractable epilepsy.
AB  - Cortical resective surgery (including amygdalohippocampectomy) and corpus
      callosotomy are the most widely accepted modes of surgical treatment for
      intractable epilepsy. Between July 1989 and May 1996, 146 surgeries for epilepsy
      were done at Severance Hospital, Yonsei University. Resective surgery was
      performed in 126 patients and corpus callosotomy in 20 patients. Of the 126
      patients who underwent resective surgery, surgery for the removal of the
      epileptic lesion (lesionectomy) was performed in 21 patients (16.7%) while 105
      patients (83.3%) underwent surgery without a structural lesion. Current surgical
      therapy for intractable epilepsy requires the precise localization of a
      resectable zone of epileptogenesis. Unfortunately, finding a localized focus in
      an extratemporal region is far more difficult than in the temporal lobe.
      Surgeries for extratemporal lobe epilepsy without lesions have been less
      successful than surgeries for temporal lobe epilepsy. Although surgery for
      intractable epilepsy has been increasingly successful, we still need to refine
      our techniques to further improve the success rate and to reduce complications of
      surgery such as language and memory impairment.

PMID- 9780405
TI  - Radiosurgery 

PMID- 9780404
TI  - Epilepsy 

PMID- 9780406
TI  - Surgical palliation of dyskinesiae in Parkinson's disease.
AB  - The history of surgical management of Parkinson's disease is outlined. Current
      practice of thalamotomy and pallidotomy is discussed. Surgical management has re
      established its role in the management of Parkinson's disease.

PMID- 9780407
TI  - Stereotactic surgery and Parkinson's disease.
AB  - With a short description of the historical background, thalamotomy and
      posteroventral pallidotomy (PVP) are introduced as effective means to alleviate
      motor symptoms in Parkinson's disease (PD). Rigidity and dopa-induced dyskinesia
      are improved and abolished by either of the two procedures, but tremor is more
      markedly improved by thalamotomy than by PVP. To date, surgical treatment has
      been important in treating PD. Also, the influence of PVP on psychological
      symptoms in PD, bradyphrenia and emotional changes offers an important key to
      understand and to interpret these symptoms.

PMID- 9780409
TI  - Brain tumors and computer-assisted neurosurgery 

PMID- 9780408
TI  - Movement disorders 

PMID- 9780410
TI  - Re: the pulled in two syndrome (PITS)

PMID- 9780411
TI  - Of deformity.

PMID- 9780412
TI  - Coincident resection-recession (tenectomy-recession) of the medial rectus muscle,
      bilaterally, for the treatment of esotropia: results in 18 cases.
AB  - PURPOSE: To study the effect of preceding tenectomy of the medial rectus tendon
      on the results of medial rectus muscle recession. SUBJECTS AND METHODS: Eighteen
      consecutive cases of incomitant esotropia were retrospectively reviewed. The
      average preoperative esotropia was 35 PD with an incomitant deviation between 10
      PD and 30 PD. All patients underwent 7 mm bilateral medial rectus muscle
      recession after 4 mm tenectomy of the anterior medial rectus muscle. RESULTS:
      Fourteen patients (78%) had "satisfactory" results (within 10 PD static
      esodeviation and 12 PD dynamic deviation [incomitance]). Four (22%) were
      undercorrected. One showed a postoperative consecutive exotropia of 4 PD at
      distance only. CONCLUSIONS: Tenectomy of the anterior muscle tendon preceding
      large recessions of the medial rectus was effective in reducing the frequency of
      overcorrection (consecutive exotropia). Undercorrection did not appear to be more
      common.

PMID- 9780413
TI  - Outcome of surgery for superior oblique palsy with contracture of ipsilateral
      superior rectus treated by superior rectus recession.
AB  - PURPOSE: To report our experience with this special subgroup of patients with
      superior oblique palsy. SUBJECTS AND METHODS: All six patients seen since 1990
      which the senior author treated who had a unilateral superior oblique palsy
      accompanied by ipsilateral superior rectus muscle contracture. Surgical
      management included superior rectus recession along with treatment of the
      superior oblique palsy by one of several appropriate procedures. RESULTS: Five
      out of six had an "excellent" surgical outcome defined as no diplopia in primary
      and reading position, elimination of their abnormal head posture and
      normalization of versions postoperatively. The sixth patient continued to have a
      small intermittent vertical deviation, but was functionally satisfactory.
      CONCLUSIONS: This subset of individuals with superior oblique palsy and
      ipsilateral rectus contracture can be improved with weakening of the ipsilateral
      superior rectus as part of the surgical plan.

PMID- 9780414
TI  - Quantification (grading) of inferior oblique muscle recession for V-pattern
      strabismus.
AB  - PURPOSE: To determine the effectiveness of grading such surgery according to the
      magnitude of the V pattern and inferior oblique muscle overaction (IOOA).
      METHODS: We retrospectively reviewed all 53 cases we operated since 1984 for V
      pattern with IOOA, who had undergone graded inferior oblique recession, recessed
      according to the anatomical recession table of Apt and Call, ranging from 8mm for
      V pattern of 12 PD with +1 IOOA to 12mm for 30+ PD with +3 IOOA. RESULTS: A
      "satisfactory outcome" (defined as = V pattern of 8 PD or less) was observed in
      75% of the cases with a preoperative V pattern less than 20 PD, in 70% of those
      with a preop' V pattern between 20 PD and 29 PD, and in 57% of those with a
      preop' V pattern greater than 29 PD. There were no overcorrections. All
      unsatisfactory outcomes were undercorrections. CONCLUSIONS: The principle of
      grading this surgery is supported and affirmed by these results. However, the
      results also suggest a need to increase the amount of surgery for all categories
      and add anterior transposition for larger V patterns.

PMID- 9780415
TI  - Historical review: Alexander Duane, M.D.

PMID- 9780416
TI  - Grand rounds #51: a case of consecutive exotropia after medial rectus recession
      for Duane syndrome.

PMID- 9780417
TI  - Re: Portal JM, Romano PE: Ocular dominance, central, etc. and baseball.

PMID- 9780419
TI  - [Body mass index: a new start in the metabolic syndrome X constellation?].

PMID- 9780418
TI  - Ocular dominance, central, etc. and baseball 

PMID- 9780420
TI  - [Body mass index influence in the insulin action mechanisms].
AB  - OBJECTIVE: Improve the knowledge of the "in vitro" insulin action in healthy
      subjects with different body mass index (BMI), in order to know the role of
      obesity in the diabetes mellitus. MATERIAL: In 12 healthy subjects with different
      BMI and normal oral glucose test we made a gluteal biopsy to obtain adipose
      tissue. In the isolated adipocytes we studied the interaction of insulin with its
      receptor and the glucose transport. RESULTS: BMI was not correlated with the
      maximal specific 125I-insulin binding but was negative when correlated with the
      glucose transport in basal situation (r = -0.63, p < 0.05) as well as when
      stimulated with insulin (r = -0.67, p < 0.05), when the results were expressed as
      number of cells. When the data were expressed as surface, BMI was negative
      correlated with the percentage of maximal specific 125I-insulin binding (r = 
      0.81, p < 0.05), and also with the basal glucose transport (r = -0.69, p < 0.05)
      and stimulated with insulin (r = -0.77, p < 0.01). CONCLUSION: The increase of
      BMI is an important diabetogenic agent, acting at receptor as well as at
      postreceptor level, and the data should be expressed according to the cellular
      diameter rather than to the number of cells in subjects with different BMI. A
      cutting point was established at the 30 BMI level after which the described
      alterations could be observed.

PMID- 9780422
TI  - [Tuberculosis and HIV infection. Clinical characteristics and diagnosis].
AB  - OBJECTIVE: To analyze the clinical characteristics and diagnose of tuberculosis
      in patients infected by human immunodeficiency virus in our setting. METHODS: We
      have revised the clinical, microbiological and histological characteristics of 92
      cases diagnosed tuberculosis in seropositive patients, during a span time of 128
      months. RESULTS: Of them, 71 were male and most of them (81.5%) were intravenous
      drugs users. The most (93.4%) were sintomatic when tuberculosis was diagnosed
      mainly fever and general and respiratory sintomatology. The most common signs
      were the presence of lymphadenopathies and hepatomegaly. The tuberculosis
      affected mainly pulmonary and ganglionary system. 34 cases had only pulmonary
      pathology, 24 extrapulmonary, 25 pulmonary and extrapulmonary and 9 miliary. The
      tuberculosis diagnose was based in microbiologic criteris. The most frequent
      source, as histologic critery, has been the ganglionary tissue. CONCLUSIONS: The
      only or associated pulmonary forms are more frequent. The most commonly
      extrapulmonary form is the ganglionary localization. The most of diagnose methods
      were obtained from respiratory tract and lymphadenopathy samples.

PMID- 9780421
TI  - [Discriminative value for AIDS case of erythrocyte sedimentation rate,
      immunoglobulins IgA and IgM, and beta 2-microglobulin in combination with the
      CD4+ lymphocyte count].
AB  - OBJECTIVE: To establish the probability to discriminate the evolution to "AIDS
      case" in relation to the common laboratory parametres in the follow-up of the HIV
      infection. MATERIAL AND METHODS: We have studied a cohort of 118 patients (1986
      95) with HIV infection, 14 of them (12%) had clinical criteria for AIDS (CDC/93)
      during the follow-up. Clinical evaluations and CD4+ and CD8+ lymphocytes, beta
      2M, IgG, IgA, IgM and E.S.R determinations were done. Multivariate analysis
      (RSIGMA) was done. with the initial laboratory values, according to the clinical
      diagnostic (AIDS and NO AIDS) done during the follow-up. RESULTS: By multiple
      logistic regression those laboratory variables with more predictor value for
      "AIDS CASE" were selected. With the initial value of these variables (E.S.R.,
      beta 2M, IgA, IgM and CD4+ lymphocytes) and the clinical diagnostic of AIDS done
      during the follow-up, we did the linear discriminatory analysis between two
      groups (AIDS, NO AIDS) obtaining generalized distance between both groups of
      3,4609 and a probability of classification error of 4%. A very significant
      difference (p < 0.001) was obtaining when we compare the variables' mean of each
      of the clinical groups. CONCLUSION: In the HIV infection the values of ESR, beta
      2M, IgA and IgM in combination with the absolute value of the CD4+ lymphocytes
      allows to discriminate those patients who will develop AIDS with a probability of
      classifications error of 4%. This has clinical interest in absence of viral load
      and helps to take therapeutical decisions.

PMID- 9780424
TI  - [Dystomatosis produced by fasciola hepatica: three cases in Madrid].
AB  - Three cases of hepatic fascioliasis diagnosed in the Department of Internal
      Medicine are presented. All of the patients live in Madrid, all were fed
      watercress in the last month and the diagnosis was established during the
      invasive phase and confirmed by serological testing. We emphasized the importance
      of the TC scan in the correct diagnosis, the ectopic location of the parasite
      presentation like subcutaneous thoracic nodule and the efficacy of bithionol in
      the treatment.

PMID- 9780423
TI  - [Community acquired pneumonia requiring admission to hospital. Etiology and
      follow-up of 366 cases].
AB  - An eighteen-month prospective study designed to determine the incidence, etiology
      and prognosis of community acquired pneumonia (CAP) in adults requiring admission
      to hospital. METHODS: We studied 366 patients admitted to hospital after being
      diagnosed of CAP at the Emergency Room of a General Hospital. Standard laboratory
      methods were used for culture from blood and sputum, and serology tests for
      Legionella pneumophila. Mycoplasma pneumoniae, Chlamydia psittaci and Coxiella
      burnetti. Patients were evaluated until complete recovery, paying special
      attention to prognostic factors predictive of death. RESULTS: An etiological
      diagnosis was established in 99 patients (27.6%). Legionella pneumophila was the
      most common pathogen accounting for 30 cases (8.2%), followed by Streptococcus
      pneumoniae with 26 cases. 26 patients died (mortality rate of 7%); factors
      predictive of death included pre-existing disease, tachypnea and elevated blood
      urea nitrogen level. CONCLUSIONS: CAP represented 4.4% of admissions. Legionella
      pneumophila was the most frequently identified pathogen. If tachypnea and/or
      uremia are noted on admission, there is an increase in the risk of death.

PMID- 9780425
TI  - [Bacteremia by Corynebacterium striatum and neutrocytic ascites. Presentation of
      a case and review of the literature].
AB  - Corynebacterium striatum is a Gram-positive pleomorphic bacillus that has been
      regarded as a saprophyte of mucous membranes and skin. There are certain
      difficulties in identifying the Corynebacteria species in the laboratory and it
      is often necessary to resort to techniques which are not available in all
      laboratories. Over recent years, C. striatum has shown itself to be a potential
      pathogen generally in weakened or immunodepressed individuals, in relation with
      intravenous catheters and in intensive care units. We report a case of bacteremia
      by C. striatum and neutrocytic ascites probably related to that microorganism,
      and, in view of the rarity of this isolement, we have reviewed the cases
      published on this subject.

PMID- 9780426
TI  - [Intercostal neurofibroma in a patient with von Recklinghausen's disease.
      Diagnostic utility of helical CT and nuclear magnetic resonance].
AB  - A 44 year-old man with a type I Neurofibromatosis (NFI) and an intercostal mass
      is presented. By means of percutaneous fine needle aspiration punction under CT
      control, this tumor could be diagnosed of neurofibroma. It is important to remark
      not only the role of helical CT with anatomical reconstruction in the diagnosis
      of intercostal tumors, but also that intercostal location of neurofibromas has
      been rarely reported in the literature. Because of frequent association between
      NFI and neoplasms, it is always necessary to perform histological study of every
      new tumor that appears in the course of this entity.

PMID- 9780427
TI  - [Psoas abscess secondary to lumbar spondylodiscitis caused by gram negative
      bacilli].
AB  - The association between psoas abscess and lumbar spondylodiscitis by Gram
      negative bacilli represents a rare clinical entity. Sometimes the absence of
      demonstrative symptoms complicates the diagnostic schema. We report about a 72
      year-old woman, without previous known diabetes mellitus, who was admitted
      because of fever of one week duration and a non-ketotic hyperosmolar coma. A left
      psoas abscess was identified by abdominal computed tomography (CT). The abscess
      was in communication with the L1-L2 intervertebral space. Although Escherichia
      coli was identified as the causing agent and appropriate antibiotic therapy was
      administered, the resolution of the abscess occurred only after the implantation
      of a percutaneous catheter guided by CT without additional surgery. Percutaneous
      drainage as a diagnostic-therapeutic technique has rendered the surgery as the
      last resort in the treatment of psoas abscess.

PMID- 9780428
TI  - [Which are the vaccines that human immunodeficiency virus infected patients must
      receive?].
AB  - Patients with aids are at increased risk of opportunistic and non opportunistic
      infections. It is now known that the incidence can be reduced by prophylactic
      measures and/or the use of vaccines. HIV infection produces an elevated frequency
      of severe pneumococcal disease with a rate of bacteriemia caused by Streptococcus
      pneumoniae 150-300 fold greater than rates reported in non-HIV infected people.
      For this reason, pneumococcal vaccine should be administered as early as possible
      in the course of the infection. Besides, the antibody response may be
      significantly higher for asymptomatic persons. Acute hepatitis caused by
      hepatitis B virus is milder than in non HIV infected patients but chronic disease
      is more frequent. The prognosis is worse and there is higher risk for infecting
      another persons. Hepatitis B vaccine is indicated for all the patients with HIV
      and negative serology for hepatitis B virus. Influenza vaccine is of limited
      effectiveness due to the high variability of the virus. Besides, influenza
      incidence is low among approximately young adults, HIV related immunodeficiency
      increased influenza risk only minimally, the vaccine is administered yearly and
      HIV-replication can increase in temporal association with vaccination. For all
      these reasons, fewer hospitalizations and deaths are prevented making it a far
      less cost-effective prevention strategy than pneumococcal vaccination. The risk
      of Haemophilus influenzae infections is elevated, but the vaccine is not
      routinely recommended because the more frequent serotype in HIV infected patients
      is b. For these subjects, passive immunization with immunoglobulin may also be
      necessary to provide protection. In conclusion, pneumococcal and hepatitis B
      vaccination is a reasonable prevention strategy for HIV infected patients at all
      stages of immunodeficiency. Influenza and H. influenzae vaccination are not
      recommended and alternative prevention strategies may be done.

PMID- 9780429
TI  - [The good doctor].

PMID- 9780430
TI  - [Cooperation. Relationship between district and referred medical center
      services].
AB  - Theoretic basis of cooperation relationship between organizations are reviewed.
      Second one, these theoretic concepts are applied to the relationship between
      district and reference medical Centers and Services, focusing on main problems of
      that relationship. The relevant role of communication and its new technologies
      are also discussed.

PMID- 9780432
TI  - [Rhabdomyolysis associated with measles in a young adult].

PMID- 9780431
TI  - [Acetazolamide induced acute renal failure without evidence of renal
      obstruction].

PMID- 9780433
TI  - [Citrobacter freundii, a rare cause of hepatic abscess].

PMID- 9780434
TI  - [Prevalence of serologic markers of hepatitis virus infection in local police].

PMID- 9780435
TI  - [Hyperthyroidism and anemia of chronic disorders].

PMID- 9780436
TI  - [Hepatitis C virus pathogenic potential].

PMID- 9780437
TI  - [Mycobacterium marinum skin infections, apropos of a case].

PMID- 9780438
TI  - [Ondansetron for cholestatic pruritus].

PMID- 9780439
TI  - [Forecast of the beginning day of Japanese cedar pollen release using variation
      pattern in air temperature].
AB  - It is important to forecast the beginning day of Japanese cedar pollen release
      for taking the preventive medical measure. We analyzed the relation between the
      beginning day of pollen release and the changing pattern of daily air
      temperature. A simple and practical method for forecasting the beginning day of
      pollen release is suggested. Polynomial of degree three was applied to represent
      the general variation pattern of air temperature. Multiple correlation
      coefficients between parameters of the polynomial and the beginning days of
      pollen release were 0.88 for the difference by year, and 0.81 for the difference
      by place. It was shown that the minimum value and the date of the fitted
      polynomial curve were related closely to the difference in the beginning day of
      pollen release by year. The minimum value and the date of the original series of
      air temperature showed high correlation with the difference in the beginning day
      of pollen release by place. We propose to use the minimum value and the date of
      original series and fitted curve of air temperature for forecasting the beginning
      day of cedar pollen release.

PMID- 9780440
TI  - [Food and food additives hypersensitivity in adult asthmatics. I. Skin scratch
      test with food allergens and food challenge in adult asthmatics].
AB  - OBJECTS: The aim of this study was to investigate in adult asthmatics, which
      kinds of food allergen can cause a positive reaction by skin scratch test and
      cause symptoms when administered as a food challenge. SUBJECTS AND METHOD: Three
      thousand one hundred and two adult asthmatic patients were submitted to skin
      scratch tests with housedust mite. Japanese cedar extracts and 33 types of food.
      Sixty one adult asthmatic patients with a history of immediate, adverse reactions
      after food ingestion underwent open food challenge. RESULT: Six hundred and
      twenty five of 3102 subjects (20.1%) had a positive test to one or more food
      allergens. The commonest food allergens were shrimp (27.7%), crab (27.7%), yeast
      (23.8%) and buckwheat (15.8%). The positive tests of shrimp, egg and cow's milk
      were highest in patients under 20 years and decreased with age, however the test
      rates of crab and soybean were not influenced by age. Positive food challenge
      responses occurred in 30/60 subjects (50%). The foods, which most of ten provoked
      a reaction, were buckwheat, shrimp, crab and bread. CONCLUSION: Skin scratch test
      results in adult asthmatics were different from those in atopic children where
      the commonest foods with positive tests were egg, cow's milk and soybean. Except
      for patients with a previous life-threatening reaction. Food allergy should be
      diagnosed by food challenge where a patient's history of adverse reaction to
      food, positive skin test and RAST strongly support specific food reactivity.

PMID- 9780441
TI  - [Chlamydia pneumoniae infection in children with asthma exacerbation].
AB  - Little is known about the significance of C. pneumoniae in wheezing state in
      children. In this study, a total of 33 children with exacerbation of bronchial
      asthma were serologically and bacteriologically analyzed to investigate whether
      C. pneumoniae infection is associated with wheezing in children with bronchial
      asthma. 1) Of the 33 patients 12 (39%) had an acute antibody rise against C.
      pneumoniae. C. pneumoniae was isolated from 8 patients (24%) by culture. Based on
      these findings, 15 cases (45%) were diagnosed as C. pneumoniae infection. 2)
      There were no significant difference in clinical signs, symptoms and laboratory
      studies between with and without C. pneumoniae infection. The high incidence of
      C. pneumoniae infection in children with exacerbation of bronchial asthma
      suggests its significance as a cause of wheezing. Although there was no specific
      symptom in C. pneumoniae infection, this infection should be suspected in
      wheezing children for diagnosis and proper treatment.

PMID- 9780442
TI  - [Measurement of theophylline concentrations by AccuMeter--comparison with the EIA
      method].
AB  - Theophylline is widely used for treating patients with bronchial asthma. However,
      since the therapeutic concentration range is narrow, adverse reactions are
      frequent and often difficult to control, making monitoring of theophylline
      concentration mandatory for its efficient and safe use. In this study, we
      employed the AccMeter which allowed us to measure theophylline concentrations
      quickly and with ease, and compared it with EIA method. AccMeter is a kit which
      consists of two parts. One part consists of a chromatopaper with antitheophylline
      mouse monoclonal antibody fixed on it, on which a smaple is applied with enzyme
      linked theophylline. The other part consists of a coloring solution. We used a
      part of arterial blood samples collected for gas analysis as trial samples. Both
      whole blood and plasma from 50 patients who did or did not receive theophlline
      were analysed. Plasma portions were also used for measurements by the EIA method.
      Results from all three measurements were almost identical, and showed good
      correlation. The time necessary for measurement using AccMeter was about 20
      minutes. We consider this method to be useful for clinics due to its simplicity
      and ease of handling, and the accuracy of the results obtained.

PMID- 9780443
TI  - [Safe administration of influenza vaccine in asthmatic children].
AB  - Thirty asthmatic children were examined allergic reaction against egg white,
      gelatin and vaccine solution before and after vaccination using skin prick test.
      We also measured the levels of specific IgE and IgG antibody against gelatin. The
      changes in clinical symptoms before and after vaccination were investigated in 25
      asthmatic children by evaluating symptom and treatment score. The results were as
      follows; 1. In one subject who had delayed type of skin reaction to gelatin, the
      adverse reaction was also recognized at the skin site around 24 hrs after
      vaccination. In this subject, the levels of serum specific IgE and IgG to gelatin
      became positive after 5 months. 2. Specific IgE antibodies to gelatin were not
      detected in all subjects before and after vaccination. 3. The mean values of
      asthma symptom score before and after vaccination were 3.3 +/- 4.2 and 1.5 +/-
      3.3 respectively. Those of treatment score before and after vaccination were 75.6
      +/- 35.2 and 76.0 +/- 35.0 respectively. These results suggest that skin testing
      with gelatin and vaccine solution is useful as a screening method for predicting
      adverse reactions in asthmatic children and that influenza vaccination can be
      performed safely in skin test negative children.

PMID- 9780444
TI  - [Respiratory symptoms by oral challenge tests with egg white antigens in egg
      allergic children].
AB  - One hundred and ninety one subjects showing histories of immediate hypersensitive
      response to egg white ingestion and/or positive IgE antibody titers specific for
      egg white were enrolled in double-blind placebo-controlled oral challenge with
      freeze and dried, heated or heated and ovomucoid-depleted egg white antigens.
      Seventy seven were male and 114 female, and their ages ranged from 11 month to 10
      years 5 month; 118 of them had atopic dermatitis, seven had asthma and 33 had
      both atopic dermatitis and bronchial asthma and 33 had urticaria. One hundred
      four children developed 147 positive symptoms including 131 immediate reactions
      and 16 non-immediate reactions by oral challenge tests. Respiratory symptoms were
      observed in 25 cases (17%) including cough alone in 12 cases (8.2%), and both
      wheezing and cough in 13 cases (8.8%). These were all observed as immediate
      reactions and accompanied with dermal symptoms. Frequency of respiratory symptoms
      correlated with specific IgE antibody titers for egg white. Heated and ovomucoid
      depleted egg white was more hypoallergenic that heated or freeze and dried egg
      white with respect to respiratory symptoms as well as other symptoms. We
      concluded that respiratory symptoms were provoked through oral challenges with
      egg white in a part of egg-allergic children.

PMID- 9780445
TI  - [Cough-variant asthma successfully treated with suplatast tosilate].

PMID- 9780446
TI  - [WHO position paper. "Allergen immunotherapy: therapeutic vaccines for allergic
      diseases"].

PMID- 9780447
TI  - Immunization against hepatitis A during an outbreak in a Jewish Orthodox
      community--Quebec, 1997-1998.

PMID- 9780449
TI  - Abraham Jacobi and German medical radicalism in antebellum New York.

PMID- 9780448
TI  - Intentional ignorance: a history of blind assessment and placebo controls in
      medicine.

PMID- 9780450
TI  - A crippling fear: experiencing polio in the era of FDR.

PMID- 9780451
TI  - Where is the postcolonial history of medicine? Essay review.

PMID- 9780452
TI  - [The digital Holter system: problems and potentialities as a non-invasive
      electrophysiological test].

PMID- 9780453
TI  - [New technology and methods for analysis of representation of signal variability
      in ventricular repolarization].

PMID- 9780454
TI  - [Variability of heart rate: short and long-term analysis].

PMID- 9780455
TI  - [Identification of frequency-dependence in cardiac arrhythmia: methods and
      implications].

PMID- 9780456
TI  - [The dispersion of ventricular repolarization diagnosed by Holter: limitations
      and possibilities].

PMID- 9780457
TI  - [Silent myocardial ischemia: clinical relevance in hypertensive patients].

PMID- 9780458
TI  - [Myocardial ischemia in exertion: correlation of the Holter and ergometric test].

PMID- 9780459
TI  - [Epidemiologic and socioeconomic aspects of venous disease].

PMID- 9780460
TI  - [Severe venous thrombosis in pulmonary embolism: physiopathological aspects].

PMID- 9780461
TI  - [Diagnosis of severe venous thrombosis].

PMID- 9780462
TI  - [Prevention of severe venous thrombosis in pulmonary embolism].

PMID- 9780463
TI  - [Treatment of severe venous thrombosis].

PMID- 9780464
TI  - [Treatment of pulmonary embolism].

PMID- 9780465
TI  - [The caval filter in prevention of pulmonary embolism].

PMID- 9780466
TI  - [The effect of thrombolytic treatment on the development of global and regional
      left ventricular function].

PMID- 9780467
TI  - [Evaluation of ischemic risk in infarct patients submitted for fibronolysis: how
      and when should it be carried out?].

PMID- 9780468
TI  - [The clinical importance of myocardial vitality in chronic, postischemic left
      ventricular dysfunction].

PMID- 9780470
TI  - [Management of infarct patients submitted for fibrinolysis: the role of the
      intervention procedure].

PMID- 9780469
TI  - [The recovery of vital contractile myocardium in coronary revascularization
      surgical intervention].

PMID- 9780471
TI  - [Endostatin and angiostatin: two weapons, a single target].

PMID- 9780472
TI  - [6th International Conference. Adjuvant therapy of breast cancer in the first
      stages. 26-28 February 1998, St. Gallen, Switzerland].

PMID- 9780474
TI  - [Efficacy and tolerability of methotrexate in the treatment of rheumatoid
      arthritis].
AB  - OBJECTIVE: To verify, in an open study, the efficacy and safety of long-term
      administration of low weekly doses (5 mg) of methotrexate (MTX) i.m. in different
      stage rheumatoid arthritis patients. PATIENTS AND METHODS: The study has been
      performed for 24 months in 42 patients (37 females and 5 males), fulfilling the
      ARA criteria for rheumatoid arthritis. Main functional parameters, main
      serological data and some immunology indexes were periodically monitored (after
      1, 3, 6, 12 and 24 months of therapy); moreover, some instrumental exams (X-ray
      of involved joints, liver ultrasound, respiratory function tests) have been
      performed. RESULTS: Thirty of 42 enrolled patients completed the whole 24 month
      therapy, and 22 are still using methotrexate. Results were as follows:
      therapeutic remission in one patient, marked improvement in 12 cases, moderate
      improvement in 16 and worsening in 1. Among the 12 remaining patients, 2 refused
      further treatment; 6 and 4 patients were withdrawn from the study because of
      inefficacy and toxicity, respectively. A significant improvement was observed in
      all of the main efficacy parameters taken into consideration. Moderate and
      reversible side effects were registered in 23 patients. CONCLUSIONS: Our results
      confirm the value of MTX in the treatment of rheumatoid arthritis. In our opinion
      this drug is very effective even in a relatively early stage of the disease,
      mainly in patients whose genetic and clinical markers may predict a more
      aggressive and severe outcome.

PMID- 9780473
TI  - [Sequential therapy with methotrexate and 5-fluorouracil in patients with
      advanced colorectal cancer pretreated with 5-fluorouracil plus folinic acid].
AB  - PURPOSE: To evaluate the efficacy and toxicity of a sequential low-dose
      methotrexate (MTX) and 5-fluorouracil (5FU) regimen in the palliative treatment
      of patients with advanced colorectal cancer. PATIENTS AND METHODS: Enrolled in
      the study were patients with advanced colorectal cancer, refractory to 5FU + FA.
      Patients were treated with MTX 40 mg/m2 i.v. bolus d 1 and 8, 5FU 700 mg/m2 i.v.
      bolus d 2 and 9 (24 hours after MTX bolus). The cycle was repeated every 4 weeks.
      RESULTS: 48 patients entered the study, and 45 are evaluable. The overall
      response rate was 15% with 1 complete response and 6 partial responses. Eight
      patients obtained disease stabilization. Median time to progression was 9 months.
      Toxicity was mild. Grade 3 stomatitis was observed in 7 (15%) patients.
      CONCLUSIONS: Sequential MTX/5FU is a well tolerated regimen with mild antitumor
      activity in refractory advanced colorectal patients.

PMID- 9780475
TI  - Effect of L-carnitine on plasma lipoprotein fatty acids pattern in patients with
      primary hyperlipoproteinemia.
AB  - PURPOSE: To investigate the effect of L-carnitine (L-C) administration on plasma
      lipoprotein fatty acids pattern in patients with primary hyperlipoprotinemia.
      PATIENTS AND METHODS: The effect of L-C on plasma lipoprotein fatty acids pattern
      was investigated in 24 male and female hyperlipoproteinemic patients, aged 51.3
      +/- 7.8 years (lipoprotein phenotypes: IIb and IV, WHO, 1970). After
      hypolipidemic diet (P, 22%; C, 48%; L, 30%; S, 10%; M, 10%; PV, 10%, cholesterol
      < 300 mg/d) lasting 30 days, L-C was given at a daily dosage of 1 g t.i.d. for 90
      days. RESULTS: Plasma total polyunsaturated to saturated fatty acids ratio (8/5)
      showed a statistically significant increase after L-C (baseline: 0.74 +/- 0.2, vs
      120 days: 0.84 +/- 0.2; p < or = 0.03). A statistically significant decrease of
      HDLs 16:0 (baseline: 28.1 +/- 4.2 vs 120 days: 26.4 +/- 3.7; p < or = 0.002),
      HDL3s 16:0 (baseline: 28.6 +/- 4.5 vs 120 days: 26.9 +/- 3.6; p < or = 0.001) and
      VLDLs 14:0 (baseline: 2.0 +/- 0.8 vs 120 days: 1.6 +/- 0.6; p < or = 0.02),
      specular to a statistically significant increase of VLDL's 18:2 (baseline: 21.9
      +/- 5.1 vs 120 days: 24.3 +/- 4.9; p < or = 0.01), was also observed. Plasma
      levels of total cholesterol and LDL-cholesterol were reduced after one month.
      Plasma apolipoprotein AI and B levels were significantly increased after 30 and
      60 days of treatment with L-C. CONCLUSIONS: A less atherogenic plasma lipoprotein
      fatty acids profile was observed after 120 days of combined treatment with diet
      and L-C.

PMID- 9780477
TI  - [Clinical-epidemiological study of the efficacy of thermal therapy in
      gastroenterologic diseases].
AB  - PURPOSE: To evaluate the therapeutic effects of drinking mineral water, its
      influence on gastrointestinal drug consumption as well as on working days missed
      in patients with dyspeptic syndrome or chronic constipation due to irritable
      bowel syndrome. MATERIALS AND METHODS: A questionnaire was sent to 1500
      physicians and 965 forms were available concerning patients who had mineral water
      treatment at Montecatini. RESULTS: Mineral water therapy determined a striking
      short- and medium-term improvement on clinical symptoms. Furthermore, this
      treatment reduced gastrointestinal drug consumption per year, as well as the
      number of working days missed. CONCLUSIONS: This epidemiological study confirms
      the utility of drinking mineral water in the treatment of some gastrointestinal
      syndromes either in the short and in the medium run.

PMID- 9780476
TI  - [Phase II study of docetaxel in patients with advanced stage soft tissue
      sarcoma].
AB  - PURPOSE: To evaluate the activity and toxicity of docetaxel (TXT) as second line
      therapy in advanced soft-tissue sarcoma. PATIENTS AND METHODS: Adult patients
      (pts) with histologically proven locally advanced or metastatic soft tissue
      sarcoma, were treated with TXT at a dose of 100 mg/m2 in a 1-hour i.v. infusion
      every 21 days and steroid premedication with oral prednisone 50 mg twice a day
      for five days starting 24 hours prior to TXT. RESULTS: From November 1995 to May
      1997, 19 pretreated pts entered the trial. Characteristics of the pts:
      males/females 11/8, median age 58 years (30-74), median WHO performance status 1
      (0-2); histotypes: leiomyosarcoma 6 pts, malignant fibrous histiocytoma 6 pts,
      fibrosarcoma 2 pts, others 5 pts. No objective responses were seen. The disease
      remained stable in 8 pts (42%). Median time to progression was 3.5 months (range,
      2-8), median survival 6 months (range, 2-20). The treatment was well-tolerated:
      the main side effect was hematological toxicity with G3/4 leukopenia and
      neutropenia in 58% of the pts; G3 anemia and thrombocytopenia occurred only in 1
      case. Other toxicities were alopecia that was universal, G3 emesis in 1 pt, G3
      diarrhea in 2 pts, G3 stomatitis in 1 pt. Mild fluid retention was recorded only
      in 2 pts. CONCLUSIONS: The results of this study do not suggest the use of TXT at
      this dosage and schedule in advanced soft tissue sarcoma.

PMID- 9780478
TI  - [Efficacy of vigabatrin associated with carbamazepine in the treatment of
      epilepsy. Follow up 1993-1996].
AB  - PURPOSE: To verify tolerance and clinical efficacy of vigabatrin (VGB), a new
      antiepileptic drug, in an add-on therapy with carbamazepine (CBZ). PATIENTS AND
      METHODS: From september 1993 to december 1996, 35 patients with partial complex
      seizures (CPC) and CPC plus secondary generalization were treated, with VGB plus
      CBZ, VGB dose was 1.41 +/- 0.26 (g/die +/- SD) and CBZ 2.28 +/- 0.60 (g/die +/-
      SD). RESULTS: Patients were followed-up every 4 months showing an improvement
      between 61.5% and 68.8% from baseline. CONCLUSIONS: In all patients we observed
      an improvement during the follow-up period. Side effects were mild and well
      tolerated.

PMID- 9780479
TI  - [Indication for a modern therapy of rheumatoid arthritis].
AB  - The treatment of rheumatoid arthritis is currently based on pathogenesis and
      pathophysiology, being the etiology still unknown. At cognition and activation
      phase of rheumatoid arthritis, there is a number of potential therapeutic
      approaches, still in development and in early trials. At inflammation and even
      more at invasive phase of rheumatoid arthritis, the treatment should take into
      consideration the parallel activation of several different processes, sustained
      by the heterogeneity of cells in the inflamed synovium. The early detection of
      potential severe rheumatoid arthritis patients is crucial, in order to be able to
      adjust the treatment according to the severity of disease in each patient.
      Evaluation of genetic and clinical markers for severe disease within the sixth
      month and in any case no later than the third year of disease is recommended. As
      far as pharmacotherapy is concerned, it is useful to distinguish anti-rheumatic
      agents in symptom-modifying drugs (SM-ARDs) and disease-controlling therapy (DC
      ART). Discovering the causal agent of rheumatoid arthritis could dramatically
      change the treatment of rheumatoid arthritis. In the meantime, one can envisage a
      further development of immuno-pharmacotherapy and the introduction in the
      clinical practice of specific or selective immunotherapy.

PMID- 9780480
TI  - [Health care provided by national health services and private insurance].
AB  - Italy, as well as other European countries and the USA, is facing the necessity
      of a radical reform of the National Health Service in the context of more general
      social reforms. Two types of management, state- or private-funded, are coming
      under analysis in the attempt to define how to provide effective assistance to
      all citizens in need. The efficient but restrictive services provided by private
      insurances are compared here to the somehow inefficient but more supportive forms
      of care provided by state-financed services. The necessity to implement a cost
      effective but well-operating system will most probably rely on a tight linkage
      between the public and the private care providers. Such mixed forms of Health
      Services, with the additional help of charities, will be able to provide the
      essential assistance to all in need, and an effective care to citizens full aware
      of the necessity to fairly contribute to their personal and community care.

PMID- 9780481
TI  - [Primary biliary cirrhosis].
AB  - PURPOSE: To discuss exhaustively: clinical, serological and pathologic aspects of
      primary biliary cirrhosis (CBP); recent advantages in the knowledge of the
      disease's pathogenesis, therapeutical approaches that still appear less
      preferable than liver transplantation. DESIGN: We reviewed the most important
      recent studios on CBP. RESULTS: More than 90% of patients have antimitochondrial
      antibodies, so that CBP can be considered an autoimmune disease. Inciting agents
      could be either PDC E2-like or MHC molecules. An autoaggressive mechanism against
      biliary ducts could be the following: the neo-antigen on the surface of biliary
      tract cells could be the target for the immunological damage; anti PDC-E2
      antimitochondrial antibodies could be secondary to the cellular damage and to the
      release of mitochondrial enzymes. CONCLUSIONS: In primary biliary cirrhosis,
      several circumstances (specificity of biliary-ductal destruction, lymphocyte
      infiltration of portal tract, abnormal expression of HLA-DR on surface of biliary
      epithelium cells) suggest that the epithelial cells of intrahepatic biliary ducts
      are the target of a severe and isolated immune response. The identification of
      the E2-like PDC antigen is a significant achievement in the knowledge of the
      pathogenetic process. On this basis, it is now to investigate possible genetic
      markers of risk and to clarify the role of T cells in the immunopathogenesis of
      the illness. The only effective treatment for CBP is liver transplantation.

PMID- 9780484
TI  - Regulation of skin piercing businesses.

PMID- 9780482
TI  - [Sulbactam-ampicillin monotherapy in the ambulatory treatment of pneumonia.
      Results of mono-administration].
AB  - Since ampicillin, the parent drug of aminopenicillins, is hydrolyzed by
      penicillinase, it is normally used in association with sulbactam, a sodium
      penicillinate sulfone with potent inhibiting activity on type II, III, IV, and V
      beta-lactamases. The combination ampicillin-sulbactam has been found remarkably
      useful for the treatment of severe community pneumonia caused by bacteria
      resistant to ampicillin alone. Approximately 300 patients with community
      pneumonia of various degrees of severity have been treated with a single dose of
      3-4 g ampicillin-sulbactam either diluted in normal saline or in dextrose
      solution, usually associated with methylprednisolone 20 mg or betametasone 8 mg
      (tapered). As assessed by clinical and radiological findings, recovery has been
      obtained all cases.

PMID- 9780483
TI  - [Evolution of chemotherapy of cancer. The initial phase].

PMID- 9780486
TI  - Genotyping reference service for Cryptosporidium parvum: request for faecal
      specimens.

PMID- 9780485
TI  - PHLS Ethics Committee annual report.

PMID- 9780488
TI  - [Identification of the patient with acute severe pancreatitis. A prospective,
      comparative study of the Ranson and the Salvador Zubiran National Institute of
      Nutrition criteria].
AB  - Early detection of severe acute pancreatitis could represent a formidable task
      for the clinician with limited resources. We have previously proposed a series of
      parameters that can identify patients with severe acute pancreatitis. The aim of
      this prospective study was to compare Ranson criteria with those previously
      described by the authors (INNSZ criteria) in 78 patients with acute pancreatitis.
      Sensitivity, specificity, positive and negative predictive values and accuracy
      were similar in both scores. We found a good correlation (r = 0.65, p < 0.001)
      and agreement (z = 5.0, Kappa 0.69, p < 0.001) between Ranson and INNSZ criteria.
      Our results allow us to propose INNSZ severity criteria as an easy and
      inexpensive alternative in the evaluation of patients with acute pancreatitis.

PMID- 9780487
TI  - [Risk factors for the development of germ cell tumors in children].
AB  - The search for risk factors for development of germ cell tumors (GCT) in children
      who lived in Mexico City (MC). A protective, observational, case-control study
      was conducted in children under 15 years of age resident in MC, insurer by the
      Mexican Institute of Social Security. The study population was selected between
      January 1st, 1990 and December 31st, 1994. Parents of the children were
      interviewed with a 230-items precoded questionnaire, validated previously with a
      pilot study. For analysis were obtained simple frequencies and odds ratios (OR)
      and 95% confidence interval (95%CI). There were 21 cases and 105 controls. The
      most significant risk factors were winter conception (OR = 7.6, 95% CI 1.5-39.3;
      P = 0.007); low parental education level (OR = 2.9, 95% CI 1.1-7.5; P = 0.026);
      and parental combined dust and electricity exposure before pregnancy (OR = 26,
      95% CI 2.28-1291.86; P = 0.0007). during (OR8.58, 95% CI 0.89-106.55; P = 0.041)
      and after pregnancy (OR = 9.66, 95% CI 0.99-120.22; P = 0.027). There was a
      protective effect with repetitive infections during infancy. In conclusion,
      Winter conception is in accordance with infectious etiology theory of GCT
      development. The low parental education level and the combined exposure to dust
      and electricity are very important. The protective effect of repetitive
      infections and other factors make necessary more epidemiologic studies in this
      field.

PMID- 9780489
TI  - [Gunshot injuries in the pediatric area].
AB  - Gunshot and air weapon wounds in children have become a significant source of
      morbidity and mortality in our community in the last four years. Ninety five
      children, 15 years of age and younger, were admitted to the Pediatric Surgical
      Service for gunshot and air mechanism wounds during this period. Review of the
      circumstances of injury revealed that more than 50% were accidental 71% were male
      patients, and 65% were caused by gunshots and outside of the home. Thoracic
      region was affected in 42%; abdomen, 20%; skull, face and neck, 13.4%; lower
      extremities, 13.4%; upper extremities 9%; genitalia, 2.0%; and perineal region,
      0.8%. Rapid resuscitation and triage of major injury allowed us a survival of
      97%. Social service intervention and educational task can offer significant
      benefit to these children but, ultimately gun control laws with strict
      enforcement are needed to stop this type of violence toward children.

PMID- 9780491
TI  - [Modern clinical medicine].

PMID- 9780490
TI  - [Cervico-uterine cancer. Influence of cell and viral genes. Implications in the
      development of vaccines].
AB  - Human cancer is a major public health problem; in particular, uterine-cervix
      carcinoma is frequent in most latin American countries. Activated cellular
      oncogenes (myc and ras, for example) and inactivated anti-oncogenesis (p53 or Rb)
      participate in multistep carcinogenesis. In addition, some viruses are associated
      with human cancer. For example, high risk human papillomaviruses (HPV) are
      involved in uterine-cervix carcinomas. Typification of HPV is important for
      clinical diagnosis and prognosis of this disease. The understanding of the
      biochemistry and molecular genetics of tumor suppressor genes, cellular oncogenes
      and tumor viruses has opened up new possibilities for diagnosis, vaccination and
      therapy of uterine-cervix carcinoma.

PMID- 9780492
TI  - [Retirement of the physician].

PMID- 9780493
TI  - [Results of the histopathologic registration of neoplasms in Mexico 1995].

PMID- 9780494
TI  - [Medicine and enlightenment in New Spain].
AB  - Fundamental ideas of the cultural movement of Enlightenment were drawn up and
      encouraged in England by John Locke and introduced into continental Europe by
      Voltaire. The essence of this movement was defined by I. Kant in 1784. These new
      ideas were projected into the field of medicine initially with the
      systematization of anatomical studies by Winslow, Vicq d' Azyr and Senac in
      France, by S. Th. Sommerring and von Haller in Germany, and by Paolo Mascagni and
      other anatomists in Italy. This movement settled in Spain toward the middle of
      the XVIII century, due to Father Feijoo and his pupils such as Piquer and Casal.
      In New Spain, which maintained cultural and scientific relationship with the Old
      World, the leaders of the movement were Jose Antonio Alzate in the field of
      biology and Jose Ignacio Bartolache in that of medicine. These were the founders
      of the first scientific journals: the "Diario Literario" (Literary Journal) by
      Alzate (1768) and the "Mercurio Volante" (Flying Mercury) by Bartolache (1772).
      Latter this physician had to face the great epidemic outbreak of smallpox in
      1779. Due to that, he attributed great importance to the psychological aspect of
      the problem and supported the variolization proceeding introduced into Mexico by
      Doctor Henri Morel. Moreover, two scientific expeditions, which reached New Spain
      at the end of the XVIII century, allowed to systematize the study of the American
      vegetables and to acknowledge the usefulness of botany and chemistry as auxiliary
      sciences of medicine.

PMID- 9780495
TI  - [The first specialty hospitals in Latin America].

PMID- 9780496
TI  - [First medical regulations in Latin America].

PMID- 9780498
TI  - [Osteoma of the internal auditory canal. Presentation of a case and review of the
      bibliography].
AB  - Osteomas of the internal auditory canal (IAC) are an infrequent osseous lesion.
      They are usually asymptomatic. This report describes a 29-year-old woman with an
      osteoma of the left internal auditory canal and reviews the literature.

PMID- 9780497
TI  - [The first Spanish translation of the works of Claude Bernard. "Introduction to
      the study of experimental medicine". A first in Mexican medicine. 1900].

PMID- 9780499
TI  - [Neurocysticercosis localized in the fourth ventricle].

PMID- 9780500
TI  - [Advances in the study of the mechanisms of sex differentiation].

PMID- 9780501
TI  - [Magnitude of cervico-uterine cancer in Mexico].

PMID- 9780502
TI  - [When life is ending, there is the right to death with dignity].

PMID- 9780504
TI  - [Concentration of insulin-like growth factor I, IGFBP-1 and IGFBP-3 in
      postmenopausal period].
AB  - The aim of our study was to evaluate concentration of IGF I and binding proteins:
      IGFBP-1 and IGFBP-3 in postmenopausal period. We have found negative correlation
      between concentration of IGFBP-1 and BMI, especially after hormonal replacement
      therapy. 2 mg of 17 beta estradiol given orally.

PMID- 9780503
TI  - [The role of lower genital tract infection in PROM].
AB  - The authors conducted a prospective study of the role of lower genital tract
      infection in PTL and PROM in high risk obstetric population with special interest
      in pathogens colonizing the maternal tract. A total amount of 62 women within 28
      to 37 weeks of gestation were enrolled and interviewed. Subjects were cultured
      for Gardnerella vaginalis, group B streptococcus, Trichomonas vaginalis,
      Neisseria gonorrhoeae, Bacterioides fragilis, M. Hominis, U. Urealyticum,
      Chlamydia trachomatis, Candida galabrata and they were followed to delivery.
      Preterm rupture of membranes occurred in 30.6% of these pregnancies.

PMID- 9780505
TI  - [Cervical cancer Ib associated with pregnancy].
AB  - An analysis of symptoms, diagnostic methods, intra- and postoperative
      complications in 17 pregnant patients in which Wertheim-Meigs operation was done
      due to stage Ib cervical cancer, is presented in this report. The most common
      symptoms were contact bleeding and spotting (58.8%) as well as pathologic vaginal
      discharge (29.4%). 3 patient did not have any symptoms in their history. No
      bleeding occurred in patients in whom probatory specimen was taken from their
      cervix. Small 7-12 days spotting appeared in 2 out of 3 patients following
      diagnostic conisation, done in case of ca in situ or microinvasive cancer.
      Pregnancy as a such was never a cause of intraoperative difficulties or
      complications. Mean blood transfusion was 1250 ml, this is 150 ml more than in
      nonpregnant patients. Most frequent postoperative complication was retentio
      urinare (47%). 5-year survival rate of pregnant patients (82.3%) was worse than
      in nonpregnant patients (96.2%) in the same age group and in comparable expansion
      of cancer in stage Ib in postoperative histological evaluation.

PMID- 9780506
TI  - [Cervical cancer and pregnancy: prognostic value of immunological response in
      nodes and cancer stroma].
AB  - Immune response in the stroma of cancer and in regional lymph nodes with regard
      to 5-years survival rate in 17 pregnant patients in which Wertheim-Meigs
      operation due to Ib cervical cancer was done, is assessed in this paper.
      Activation and hyperplasia of T and B dependent layers of lymph nodes as well as
      infiltration by monocyte-macrophage and lympho-plasmatic mature, immunocompetent
      cells are related to good prognosis and these are most frequent in patients with
      small invasion. Lack of immune response in lymph nodes, its poor expression,
      hemolymphatic transformation, adiposis of nodes or their fibrosis was found in 5
      patients; 3 of them died within 5 years. Scare monocyte-macrophage infiltrations
      and low-differentiated lymphocytes prevailed in the stroma of cancer. Inactive
      answer in nodes and in stroma was found in 8 out of 12 patients who had deeper
      infiltration than 0.5 cm. Immunologic response in nodes and in stroma should be
      assessed as a routine method for all prognostic purposes. Patients with inactive
      immunologic response should be qualified for further treatment.

PMID- 9780508
TI  - [The clinical value of DNA ploidy in ovarian cancer].
AB  - The aim of this study was to correlate the DNA ploidy with clinical parametres in
      ovarian cancer. For assessment of DNA cellular abnormalities it was used a new
      method-flow cytometry. Diploidy was stated in 24 cases (55.8%) and aneuploidy in
      19 cases (44.2%). In comparing to FIGO staging the frequency of aneuploidy
      increased from I to IV stage and it was statistic significant. In comparing to
      vaginal ultrasound examination the difference was not so significant, but the
      most often aneuploidy was observed in solid tumors. The results of this study
      show the usefulness of flow cytometry in diagnosis of ovarian cancer.

PMID- 9780507
TI  - [Electroconization of uterine cervix efficacious method in cervical cancer
      prophylaxis: analysis of 2555 cases].
AB  - The authors tried to assess considerably of the cervical electroconisation in the
      cervical cancer prophylaxis. The 2555 women with cervical erosions were treated
      by electroconisation. The electroconisations were performed when cytological and
      colposcopical examinations were unsuspected and conservative treatment in these
      cases has failed. Histopathological studies after conisation's samples
      demonstrated in 97% cases paraphysiological cervical changes. In 3% treated women
      cervical intraepithelial neoplasia was diagnosed. In one case cervical carcinoma
      was diagnosed in postoperative material. In this study 97% efficiacy of cervical
      electroconisation was demonstrated. Authors suggest that cervical
      electroconisation is recommended method in the treatment of cervical
      paraphysiological changes and plays important role in cervical cancer
      prophylaxis.

PMID- 9780509
TI  - [Estimation of cytological smears in women with Gardnerella vaginalis infections
      of vagina and uterine cervix].
AB  - Among micro-organisms infecting vagina whose dominant genus is Gardnerella
      vaginalis anaerobic bacteria are often present. Well-known damaging tissues and
      cells features of anaerobic bacteria are taken under consideration as factors
      which are conductive to generating pathological changes in cervical epithelium.
      The aim of this study was evaluation of cytological smears (Pap smear, Gram stain
      and H + E stain) in women with Gardnerella vaginalis infections of vagina and
      uterine cervix. The research was carried out on 1180 women hospitalised in the
      prior of fourteen months in Obstetrics-Gynaecological Department of the Municipal
      Hospital in Kielce. It was proved that characteristic microscopic feature of
      vagina and uterine cervix Gardnerella vaginalis infection is the absence of
      lactic acid bacillus, Lactobacillus vaginalis in vaginal contents and a presence
      of a small number of polynuclear neutrophil leucocytes. Marker cells (clue cells)
      are easily recognised in microscopic image in vaginal smears stained by Gram's
      method as well as Papanicolaou method. High sensitivity and specificity of these
      markers suggest usefulness of cytological smears in diagnosing Gardnerella
      vaginalis infections.

PMID- 9780510
TI  - [Colposcopy images of cervix in women with Gardnerella vaginalis infection].
AB  - Among micro-organisms infecting vagina whose dominant genus is GV anaerobic
      bacteria are often present. There are reports that GV infections of vagina and
      uterine cervix, apart from their well-known negative role in obstetrics practice
      can play a role in carcinogenic processes of uterine cervix. The aim of the study
      was to assess characteristic colposcopy images of cervix in women with
      Gardnerella vaginalis infection. The research was carried out on 1180 women
      hospitalised in the period of 14 months. Many observations lead to conclusions
      that pathognomic clinic feature of Gardnerella vaginalis infection of uterine
      cervix is visible in colposcope presence of clean, translucent mucus in external
      cervical os and opaque vaginal contents in the rear vaginal vault. High hydrogen
      ion concentration in vaginal contents (pH 6.0 and over) correlates with positive
      "fishy odour test" of this contents. Gardnerella vaginalis infection of vagina
      and uterine cervix concerns women with existing erosion-type changes of uterine
      cervix. Visible in colposcopic test restless and "spotted" images visible after
      Schiller test are pathognomic colposcopic features of Gardnerella vaginalis
      infection.

PMID- 9780512
TI  - [Struma ovarii: an ovarian neoplasm].
AB  - Authors shows three cases of very rarely occurring ovarian struma. First case-
      was discovered in a patient with normal physiological hormonal activity. Second
      case--was discovered in a postmenopausal patient with hyperthyroidism and with
      endometrial carcinoma. Third case--was discovered in a postmenopausal patient,
      without any complaints, where an ovarian tumor was found during periodical
      gynaecological examination. Histopathological evaluation of the material was
      decisive for the final diagnosis.

PMID- 9780511
TI  - [The analysis of rationale in antibiotic usage in certain maternity and
      gynecological wards and analogous outpatient clinics].
AB  - The aim of this work was the analysis of the correctness of therapeutic and
      preventive use of chemotherapeutic agents by the gynaecologists in their hospital
      and outpatient treatment. 1774 orders concerning chemotherapy or antibacterial
      chemoprophylaxis in 4 chosen health institutions (2 maternity-gynaecological
      wards and 2 analogous out-patient departments) were analysed. While evaluating
      each course indications for chemotherapy, choice of drug, each dose, way and time
      of administration were considered. In analysed health institutions 22.1-40.1% of
      used chemotherapeutics were applied without reasonable indications. In 11.3-27.7%
      of indicated cases the right chemotherapeutic was not chosen properly. Improper
      dosage concerned 0.0-23.7% of analysed courses of chemotherapy. It was no
      reservation for the ways of administration of the drugs. The inappropriate time
      of usage referred to 5.6-21.4% of analysed courses.

PMID- 9780513
TI  - [Merkel cell carcinoma of the vulva].

PMID- 9780514
TI  - Population genetic characteristics of the STR Loci D21S11 and FGA in eight
      diverse human populations.
AB  - A highly polymorphic multiplex short tandem repeat (STR) system composed of
      D21S11, FGA, and the sex-typing system amelogenin (AMG) has been used to
      investigate allele frequency distributions in two Canadian Caucasian samples
      (British Columbia and Alberta), three Canadian aboriginal populations (Coastal
      Salishans from British Columbia, Ojibwa from northern Ontario, and Cree from
      Saskatchewan), and three ethnic groups from Singapore (Chinese, Malays, and Asian
      Indians). Using the automated fluorescence detection approach on an ABD 373A DNA
      Sequencer, we distinguished 20 D21S11 and 22 FGA alleles with a nearly equal
      representation of two- and four-base variants. An overlap in allele sizes for
      both STR loci across populations was observed, but frequency differences were
      noted. Statistical analysis revealed that (1) both D21S11 and FGA loci conform to
      Hardy-Weinberg equilibrium in all eight surveyed populations based on five
      different tests and (2) both STR loci are in linkage equilibrium. Results from
      the 2 x N contingency table exact tests for population differentiation
      demonstrated that the Canadian samples from two different provinces were not
      distinguishable from one another at either STR locus and therefore could be
      combined to form one Caucasian group. Likewise, Chinese and Malays from Singapore
      did not show significant differences at either STR locus. In contrast, all other
      examined populations exhibited differences deemed statistically significant. As a
      complement to our study, we compared D21S11 allele frequency distributions in 21
      worldwide populations and FGA allele frequency distributions in 14 populations.
      Many alleles never previously reported in worldwide populations were identified
      in Canadian aboriginal and Asian samples from this study. Twenty-four D21S11 and
      29 FGA alleles were distinguished in worldwide groups. Interesting similarities
      in allele frequency distribution patterns across populations suggest that the STR
      polymorphism at these loci predates the geographic dispersal of ancestral human
      populations. This study further demonstrates the utility of highly informative
      STR loci such as D21S11 and FGA in human population evolutionary history and in
      forensic medicine.

PMID- 9780516
TI  - Surnames and genetic structure of a high-altitude Quechua community from the Ichu
      River Valley, Peruvian Central Andes, 1825-1914.
AB  - Changes in isolation, inbreeding, population subdivision, and isonymous
      relationships are examined in six Quechua communities from the upper valley of
      the Ichu River in the Peruvian Central Andes (3700 m). All marriages registered
      between 1825 and 1914 in the Parish of Santa Ana were analyzed. The data (1680
      marriages) were divided into 2 periods (1825-1870 and 1871-1914) and into the 6
      villages that constitute the parish. Endogamy rates are between 81% and 100%,
      indicating high levels of reproductive isolation. The inbreeding indicated by
      isonymy (Ft, Fr, and Fn) is lower than in other mountain populations studied.
      Isonymy values, calculated from the different surname combinations made possible
      by the Ibero-American Surnames System, indicate a strong rejection of
      consanguineous marriages, particularly between patrilineal relatives, in
      agreement with the parental structure typical of Andean populations. The
      comparison between observed and expected repeated-pair values reveals a moderate
      level of subdivision within populations, which could be related to cultural and
      socioeconomic factors. Nonmetric multidimensional scaling was used to investigate
      temporal changes in the isonymous relationships among the communities. The
      results reveal a decrease in the interpopulational variability measured by
      surnames, in agreement with an increase in exogamy. Surnames and data contained
      in historical and demographic records yield reliable information, and they can be
      used to reconstruct the biological history of Amerindian populations over the
      last few centuries.

PMID- 9780515
TI  - Factors affecting population variation in eastern Adriatic isolates (Croatia).
AB  - Inhabitants of the Croatian islands of Brac, Hvar, Korcula, and the Peljesac
      Peninsula have been the subject of extensive previous studies of local population
      differentiation. Most of these studies used biological and ecological variables,
      but some also considered historical and sociological factors. In this study we
      use genetic, morphological, kinship, and language distance data, collected for
      individuals from 26 rural communities on the islands of Brac, Hvar, Korcula, and
      the Peljesac Peninsula in the Adriatic, to further explore the interaction of
      historical, sociological, and biological factors in small populations and to test
      the significance of some of these proposed causes. First, we use matrix
      correlation methods to evaluate the relationships among different types of
      distance measures. The specific measures of genetic distance used here do not
      correlate well with other measures of population distance, and it appears that
      for the studied genetic systems the populations are not strongly differentiated.
      As expected, kinship and language distances have a high degree of association.
      Morphological differences among populations seem to be more closely tied to
      kinship distances than to genetic distances. This may result from modification of
      some morphological features by environmental rather than genetic factors, or it
      may be attributed to extensive, selective, nonrandom emigration of the population
      during the first decade of the twentieth century. In the second part of our
      analysis we use matrix correlation methods to evaluate and possibly identify the
      external factors that have contributed to the population differences.
      Specifically, we use design matrices to test hypotheses that population
      differences can be explained by one of the following factors: geographic
      isolation on the islands and peninsula, distance from the mainland, geographic
      barriers within the islands and peninsula, and the historical factors that
      differentially affected the three islands and the peninsula. Most of these design
      matrices reflect geographic distances; although correlations between
      morphological variables and simple geographic distance between localities were
      not significant, correlations between these localities and a design matrix
      incorporating geographic distance along with geographic barriers, such as bodies
      of water and mountain ranges, are particularly important for explaining distances
      among kin. Design matrices provide an important tool for quantifying the
      relationship between historical and geographic factors, and measures of
      population distance.

PMID- 9780517
TI  - Comparison of skin reflectances between Bolivian lowlanders and highlanders of
      European ancestry.
AB  - I compared one genetic marker, skin reflectances, between Bolivians of European
      ancestry residing at high altitude in La Paz (3600 m; 41 boys and 65 girls) and
      at low altitude in Santa Cruz (400 m; 140 boys and 117 girls). Reflectances were
      measured at three wavelengths (425 nm, 545 nm, and 685 nm) on two different
      sites: the medial surface of the inner upper arm and the forehead. Principal
      components analysis was used to reduce age-, sex-, and surname-standardized
      reflectances to three independent components. The first principal component,
      which assesses the genetic component of melanin concentration, did not differ
      between samples, indicating that there are no significant differences between
      lowland and highland Bolivians of European ancestry with respect to the genetic
      component of skin reflectances. The second principal component, which assesses
      the influence of tanning on skin reflectance, also did not differ significantly
      between highlanders and lowlanders. Finally, the third principal component, which
      assesses the impact of vascularity on skin reflectance, was significantly lower
      in residents of La Paz than in residents of Santa Cruz, suggesting a greater
      vascularity-induced darkening of skin color in highlanders than lowlanders,
      possibly reflecting the higher hemoglobin concentrations that are typical of
      highland populations.

PMID- 9780518
TI  - Body mass index and its association with socioeconomic and behavioral variables
      among socioeconomically heterogeneous populations of Andhra Pradesh, India.
AB  - The nature and extent of relationship between socioeconomic and behavioral
      variables and body mass index [BMI = weight (kg)/height (m)2] is studied in a
      sample of 1119 individuals (456 males and 663 females), aged 18 to 75 years,
      drawn from socioeconomically diverse populations from southern Andhra Pradesh,
      India. These populations are categorized into four groups, with graded lifestyles
      toward urbanization. The BMI of the participants ranged from 12.6 to 35.1 in
      males and from 12.3 to 34.2 in females. There is an increasing trend in mean BMI
      until about 50 years, followed by a decline, indicating nonlinear nature of age
      effects. Mean BMI also increases with better socioeconomic status of the
      constituent groups and with decreased physical activity level. A trend of a
      decrease in the proportion of individuals with chronic energy deficiency and an
      increase in the proportion of obese individuals is also seen from the traditional
      Yerukala tribe (group 1) to the urbanized group 4, from the lower to the higher
      income categories, and from heavy to light physical activity types. Smokers show
      a greater proportion of obese cases compared with nonsmokers. The prevalence of
      obesity (BMI > or = 25) is 6.6% in males and 10% in females. The results of the
      analysis of variance suggest that three of the four socioeconomic and behavioral
      variables (except smoking) show significant effects on age-adjusted BMI, and the
      R2 suggests that these variables explain 27.4% of variation in males and 17% in
      females. Although income explains the largest amount of variation (24%) in males,
      followed by physical activity and group affiliation, in females group affiliation
      (12.5%), followed closely by income, accounted for most of the variation.
      Inclusion of age in the model improved explanatory power by 5-7%. The positive
      association between socioeconomic status and BMI observed in the present study is
      qualitatively different from the negative association that characterizes
      contemporary Western populations.

PMID- 9780519
TI  - Geographic differences in seasonality of preterm births in Japan.
AB  - Based on vital statistics from 1979 to 1983, we used a time-series analysis using
      the Box-Jenkins model (ARIMA model) to compare the seasonality of preterm births
      among 47 prefectures in Japan. We also evaluated the relation between seasonality
      of preterm births and temperature. According to the Box-Jenkins analysis, a
      seasonal moving average was detected for 44 prefectures. The seasonality of
      preterm births in general shows a bimodal pattern with two peaks, one in summer
      and one in winter. The most interesting result is that the peaks show a trend
      with geographic location; one peak is dominant in winter among the northern
      prefectures and the other peak is dominant in summer among the southern
      prefectures. Another important result is that the winter increase in preterm
      births is negatively correlated with mean winter temperature (R = -0.424, p =
      0.003); on the contrary, the summer increase in preterm births is positively
      correlated with the average summer temperature (R = 0.549, p < 0.001). These
      results suggest that climate-associated factors should be associated with the
      occurrence of preterm births in Japan.

PMID- 9780521
TI  - Allele frequencies of six highly polymorphic DNA loci in the Croatian population.
AB  - The allele frequency distributions in a series of Croats were analyzed for six
      unlinked polymorphic DNA loci: THO1, FESFPS, VWA01, APOB, D1S80, and D17S5. The
      allele frequencies were determined for 100 unrelated genomic DNA samples. The
      observed heterozygote frequencies of the loci ranged from 0.63 to 0.76; however,
      the the expected heterozygosity ranged from 0.68 to 0.82, with only D17S5 having
      a significant excess of homozygous phenotypes (p < 0.001). The excess
      homozygosity seen in the D17S5 system may be due to allelic drop-out and warrants
      further technical analysis of that system, given the uniform lack of significant
      deviation in the other five systems. The forensic usefulness of these systems can
      be measured using two different statistics: the power of discrimination and the
      likelihood of a coincidental match. The power of discrimination ranged from 0.85
      to 0.94 for the 6 systems with the combined likelihood of a coincidental match
      based on these 6 systems of 1 in 3.6 million, or slightly less than the
      population of Croatia. A second, more conservative estimator of the likelihood of
      a match is based on the most common phenotype for each system. If someone had the
      most common phenotype for each of the 6 systems, the chance of a coincidental
      match would be approximately 1 in 64,000. For paternity testing the usefulness of
      a system is measured by the average power of exclusion or (1-power of exclusion),
      the random man not excluded. The average power of exclusion, based on observed
      heterozygosity, ranged from 0.33 to 0.53, and the average power of exclusion
      based on the expected heterozygosity ranged from 0.39 to 0.64. The combined
      average power of exclusion was 99.2% for these 6 systems, using the expected
      heterozygosity. Based on the results of testing these six systems, there is no
      significant substructuring within the southern Croatian populations, and these
      systems provide a useful tool for forensic, paternity, and anthropological
      applications.

PMID- 9780520
TI  - Comparison of allele frequencies of eight STR loci from Argentinian Amerindian
      and European populations.
AB  - Eight STR systems (THO1, FABP, VWA, FES/FPS, HPRTB, F13A1, CSF1PO, and D6S366)
      were investigated in different ethnic groups of Argentina. Allele and genotype
      frequencies, power of exclusion, and discriminative power were investigated.
      Hardy-Weinberg expectations were calculated from heterozygosity levels. FST and G
      tests demonstrated that significant differences exist among the investigated
      populations for some of the eight STRs markers. The Wichi Indians are clearly
      separated from the Mapuche and Tehuelche, who in turn are closer to the European
      population, suggesting non-Amerindian admixture.

PMID- 9780522
TI  - Acetylator phenotypes: allele frequency in northwestern Argentina and review of
      acetylator distribution in the Americas.
AB  - We determined acetylator phenotypes by means of a sulfadimidine test and found
      that 39% of the native population of the province of Jujuy, in northwestern
      Argentina, have slow acetylators. The frequency of the allele controlling slow
      acetylation was estimated at q = 0.65 +/- 0.001. This estimate differs from those
      previously recorded in native and Mestizo American populations. A review of the
      literature on acetylator phenotypes in the Americas revealed that it is not
      possible to discern any clear pattern of distribution in relation to the
      geographic variability observed.

PMID- 9780523
TI  - Frequencies of the butyrylcholinesterase K mutation in Brazilian populations of
      European and African origin.
AB  - The frequency of the butyrylcholinesterase K mutation was calculated on the basis
      of data obtained by polymerase chain reaction primer-introduced restriction
      analysis (PCR-PIRA). The population sample was composed of 177 Brazilians: 95
      whites of predominantly European ancestry and 82 admixed individuals (European
      and African origin). The frequencies--18.4 +/- 2.8% for whites and 17.1 +/- 2.9%
      for admixed--did not differ from those previously obtained in North America,
      Scotland, Japan, and Denmark. The occurrence of the K mutation in Europeans, East
      Asians, and Africans suggests a relatively old origin for this mutation, and the
      similar frequencies found in these populations may suggest the operation of
      selective forces.

PMID- 9780524
TI  - Responsiveness to direct versus indirect hypnotic procedures: the role of
      resistance as a predictor variable.
AB  - Empirical research attempting to demonstrate that indirectly phrased hypnotic
      suggestions result in greater responsiveness than do direct approaches generally
      has not shown any differences on formal hypnotizability scales. However,
      empirical research in related areas along with clinical observation suggests that
      client resistance might be a crucial moderating variable. Specifically,
      participants with greater resistance would be expected to be more responsive to
      indirect approaches, whereas those with low levels of resistance would be more
      responsive to direct hypnotic procedures. To test this hypothesis, participants
      were given either a standardized test of hypnotic responsiveness that used direct
      suggestions (Harvard Group Scale of Hypnotizability) or a comparable indirect
      scale (Alman Wexler Indirect Hypnotic Susceptibility Scale) followed by
      administration of a measure of resistance (Therapeutic Reactance Scale). The
      hypothesis was not confirmed, in that those with higher (or lower)
      reactance/resistance did not score differently than those on either the indirect
      or direct hypnotizability measures.

PMID- 9780525
TI  - Infant communication and the development of hypnotic responsivity.
AB  - The research on the development of hypnotic responsivity indicates that it
      emerges, ex nihilo, sometime after the age of 3. The measures used to assess
      hypnotic responsivity rely on complex verbal instructions, thus precluding
      investigation of infancy. Recent research on infancy, however, suggests that the
      ontogenesis of hypnotic responsivity is likely to be found in fundamental human
      capacities that emerge in the first weeks and months of life. The aims of the
      article are threefold: (a) to demonstrate that infants possess capacities on the
      nonverbal plane of communication that are analogous to those required for
      hypnosis; (b) to identify situations in infancy that are analogous to the
      hypnotic context; and (c) to examine dispositional and relational attributes in
      infancy that may account for later individual differences in hypnotic
      responsivity.

PMID- 9780526
TI  - Primary process, hypnotic dreams, and the hidden observer: hypnosis versus alert
      imagining.
AB  - Previous research indicated that high-hypnotizable participants reported more
      primary-process mentation in hypnotic dreams than low-hypnotizable participants
      instructed to simulate hypnosis. Differences in primary process were not
      evidenced in response to instructions for a "hidden part" of the participant to
      report on the hypnotic dream. This research replicated and extended these
      findings by showing that high-hypnotizable participants (n = 20) passing the
      dream suggestion reported more primary process in their dreams than high
      hypnotizable participants instructed to remain alert and think and imagine along
      with suggestions (n = 20). Differences in primary process were not evidenced in
      response to hidden-observer suggestions, and the frequency of dream (87% hypnosis
      vs. 96% imagining) and hidden-observer responses (100% in both groups) was
      equivalent across hypnotic and nonhypnotic groups. The results provided qualified
      support for a psychoanalytic model of hypnosis: Differences in primary process
      were apparent in response to the dream but not the hidden-observer suggestion.

PMID- 9780527
TI  - Imagery and hypnotizability revisited.
AB  - The objective of this study was to correlate computer-generated imagery tasks and
      a self-report measure of imagery ability with hypnotizability, hypothesizing that
      computer-generated imagery tasks would be better predictors of hypnotizability
      than will the self-report measure. Hypnotizability of 43 subjects was assessed
      using the Hypnotic Induction Profile and the Stanford Hypnotic Susceptibility
      Scale, Form C. Imagery ability was assessed by the Visual Vividness Imagery
      Questionnaire (VVIQ) and by computer-generated imagery tasks measuring the
      ability to generate, maintain, and transform images. Although there was no
      correlation between the VVIQ and hypnotizability, the less hypnotizable subjects
      made twice as many mistakes in the spatial imagery tasks than did the more
      hypnotizables, but this difference was not statistically significant. The
      relationships among hypnotic performance, hypnotizability, and imagery functions
      are complex.

PMID- 9780528
TI  - The role of pilot studies in the economic evaluation of health technologies.
AB  - An increasing number of economic evaluations are being conducted alongside
      clinical trials. While this practice offers the prospect of collecting
      comprehensive and accurate cost data, it requires considerable time and effort.
      In the case of clinical data, key analytic decisions such as which data to
      collect and sample size are often made with reference to smaller (pilot) trials.
      However, this approach is not normally followed in the case of economic
      evaluation. This study was based on a recently completed health technology
      assessment comparing conventional radiotherapy with continuous hyperfractionated
      accelerated radiotherapy (CHART) for patients with head and neck cancer or
      carcinoma of the bronchus. In the full health technology assessment, cost data
      were available for 526 head and neck patients (314 CHART and 212 conventional
      therapy) and 286 bronchus patients (175 CHART and 109 conventional therapy). In
      order to simulate a pilot study, data were extracted for the patients recruited
      to both trials in the first 3 months. These were then compared with the full data
      set in order to assess whether such a pilot study would have given useful
      guidance on: a) the usefulness of undertaking a full study; b) the sample size
      required; and c) the important resource items for which comprehensive data
      collection would be required. Pilot studies can be helpful in determining the
      likely advantages of undertaking full economic evaluations and in identifying
      important resource items. Therefore, it is important that clinical researchers
      and research funding bodies create the necessary time window to enable such
      studies to take place. However, formal sample size calculations are more
      difficult to perform on limited data, since they also require knowledge of the
      unit cost (or prices) to be attached to the resource items and the correlation
      between costs and clinical effects.

PMID- 9780529
TI  - Empirical criteria for the selection of quality-of-life instruments for the
      evaluation of peripheral blood progenitor cell transplantation.
AB  - We propose a method for selecting quality-of-life instruments for use in phase
      III trials using the convergent validity of patient responses collected in phase
      I and II clinical trials. Two generic and two disease-specific instruments were
      administered to patients with breast cancer undergoing peripheral blood
      progenitor cell mobilization and transplantation. They included the visual analog
      scale from the EuroQoL EQ5D instrument, the SF-36, the European Organization for
      Research and Treatment of Cancer (EORTC)-QLQ-C30, and the Functional Assessment
      of Cancer Therapy instrument. No single instrument was found to have superior
      convergent validity in all domains, but the EORTC-QLQ-C30 seemed to perform
      better than the SF-36.

PMID- 9780530
TI  - What determines the choice of procedure in stress incontinence surgery? The use
      of multilevel modeling.
AB  - The purpose of this study was to identify the determinants of choice of surgical
      procedure (anterior colporrhaphy, colposuspension, or needle suspension) to treat
      stress incontinence in women. We used multilevel modeling of data on 271 patients
      in 18 hospitals in England in 1993-94. Patient-related factors included
      sociodemographic details, anatomical diagnosis, symptom severity, symptom impact,
      previous treatment, parity, comorbidity, and general health status. Surgeon
      related factors were specialty, grade, and annual volume of procedures
      undertaken. Hospital teaching status was considered. Some patient-related factors
      were associated with choice of procedure: women with a concomitant genital
      prolapse, with a history of high parity, and with no previous nonsurgical
      treatment were more likely to undergo an anterior colporrhaphy than a
      colposuspension or needle suspension (although this finding could be confounded
      by surgical specialty). In addition, women were more likely to be treated by
      colposuspension if their surgeon specialized in incontinence surgery (measured by
      annual volume of cases). Finally, being treated by needle suspension depended on
      there being a consultant surgeon familiar with the procedure at the hospital
      attended. While choice of surgical procedure depends partly on the patient's
      anatomical diagnosis, it is also dependent on the specialty of the surgeon whom
      she consults and the hospital that she attends. This variability, in turn, could
      have implications for the patient (as the relative effectiveness of the different
      procedures is unknown) and for the purchasers of care (as the relative cost
      effectiveness of procedures is also unknown).

PMID- 9780531
TI  - An economic evaluation of energy-absorbing flooring to prevent hip fractures.
AB  - An economic evaluation of energy-absorbing flooring designed to prevent hip
      fractures revealed a payback period of 10 1/2 years if only direct costs avoided
      were evaluated and just over 11 months when direct and indirect costs were
      included. Cost-effectiveness ratios of less than $0 per hip fracture prevented
      and life year saved were also estimated.

PMID- 9780533
TI  - A note on confidence intervals in cost-effectiveness analysis.
AB  - How to obtain confidence intervals for cost-effectiveness ratios is complicated
      by the statistical problems of obtaining a confidence interval for a ratio of
      random variables. Different approaches have been suggested in the literature, but
      no consensus has been reached. We propose an alternative simple solution to this
      problem. By multiplying the effectiveness units by the price per effectiveness
      unit, both costs and benefits can be expressed in monetary terms and standard
      statistical techniques can be used to estimate a confidence interval for net
      benefits. This approach avoids the ratio estimation problem and explicitly
      recognizes that the price per effectiveness unit has to be known to provide cost
      effectiveness analysis with a useful decision rule.

PMID- 9780532
TI  - The effect of a redistribution system for health care for the elderly on the
      financial performance of health insurance societies in Japan.
AB  - Health care for the elderly in Japan is financed through a pool to which all
      insurers contribute. We analyzed insurers' financial data to evaluate this
      redistribution system. Cost sharing affected financial performance substantially.
      The current formula for cost-sharing redistributes elderly health care costs
      unequally and should be changed.

PMID- 9780534
TI  - Cost-effectiveness of open versus laparoscopic repair for primary inguinal
      hernia.
AB  - A cost-effectiveness (CE) analysis was performed of Bassini versus laparoscopic
      repair for primary inguinal hernia. Incremental costs per 1-year recurrence-free
      patient were calculated for the societal and hospital perspective. From the
      hospital perspective, the incremental CE ratio of laparoscopic repair is 5.348
      guilders. From the societal perspective, laparoscopic repair is both less costly
      and more effective than Bassini repair. Results were sensitive to assumptions
      about recurrence rates, laparoscopic operating time, and return to work.
      Laparoscopic repair should replace Bassini repair in order to benefit society.
      From the hospital perspective, the decision to accept laparoscopic repair depends
      on the willingness to pay.

PMID- 9780535
TI  - Physicians' patterns of using a computerized collection of guidelines for primary
      care.
AB  - Physician's Desk Reference and Database is a Finnish collection of computerized
      primary care guidelines. The program has been in clinical use since 1989. For
      this study, a function producing a log file of all searches was added to the
      program. Two hundred twenty-seven users returned log files that contained 15,267
      searches. The users made 3.12 (range 1-10.4) searches per day. The average time
      needed to find and read an article was 4.9 minutes. Sufficient facts were found
      in 71% of the searches. Dermatology was the most popular field of interest,
      followed by infectious diseases and cardiology.

PMID- 9780536
TI  - Generalizing costs from trials. Analyzing center selection bias in a breast
      screening trial.
AB  - With a growing number of economic evaluations being conducted alongside trials,
      there is a need to address, and if necessary, investigate the generalizability of
      results derived from trials. This paper explores the generalizability of costs
      from a trial investigating the frequency of breast cancer screening in the United
      Kingdom.

PMID- 9780537
TI  - Patient and informal caregiver time in cost-effectiveness analysis. A response to
      the recommendations of the Washington Panel.
AB  - The time invested by patients and informal caregivers in treatment and
      rehabilitation should be valued in a cost-effectiveness analysis (CEA). The
      Washington Panel gives recommendations on incorporation of time costs that may
      misrepresent true societal costs. This article provides alternative
      recommendations for incorporating costs of time in CEA. Following an opportunity
      costs approach, time is separated into three parts, each with its own valuation
      methods: time spent on paid work, unpaid work, and leisure.

PMID- 9780539
TI  - Routine preoperative investigation. Results of a multicenter survey in Italy.
      Collaborator Group.
AB  - We conducted a study to acquire information on the current behavior of a sample
      of Italian surgeons and anesthesiologists about prescribing, interpreting, and
      using routine preoperative investigations. Consultants in surgery and
      anesthesiology in 60 hospitals in northern, central, and southern Italy were
      interviewed. Prescription of these procedures by doctors were driven more by
      personal experience than by updated scientific knowledge. This practice often led
      to ineffective and inefficient clinical practice, with healthy patients
      undergoing useless, time-consuming, costly, and sometimes harmful procedures.

PMID- 9780538
TI  - The cost-effectiveness of octreotide acetate in the treatment of carcinoid
      syndrome and VIPoma.
AB  - Markov modeling was used to evaluate the cost-effectiveness of octreotide in
      treating carcinoid syndrome and VIPoma. For each condition, using octreotide was
      associated with doubled survival time. Octreotide was cost-effective for treating
      carcinoid tumor ($752 per additional year of life, two additional years on
      average), and cost saving for VIPoma.

PMID- 9780540
TI  - Home drug infusion therapy. A literature update.
AB  - This paper is a literature review and update of home drug infusion therapy (HDIT)
      in the United States. It concentrates on cost-effectiveness studies of parenteral
      antibiotic therapy administered in an outpatient setting. This update is timely
      because Medicare and other payors are under the pressure of cost containment with
      respect to this modality. Additionally, managed care is redefining reimbursement
      programs, which will affect HDIT in the future.

PMID- 9780541
TI  - Ethical issues in technology assessment. Conceptual categories and procedural
      considerations.
AB  - The practice of health care technology assessment involves ethical considerations
      in all of its varied functions and techniques. Ethical issues in technology
      assessment can be grouped into the broad categories of normative concepts,
      diagnosis, prevention and therapy, research and the advancement of knowledge, and
      allocation of resources. Moreover, the ethics of the assessment process itself
      must be evaluated in terms of the integrity of the project's goals, procedures,
      and effects, and evaluators' open and self-critical acknowledgment of their
      purposes. As a relatively new field, technology assessment can benefit from using
      a variety of analytic approaches as it works to develop its own methods for
      evaluating ethical issues related to technology.

PMID- 9780543
TI  - An assessment of picture archiving and communication systems (PACS). The case
      study of the SMZO Project. Socialmedizinischenes Zentrum Ost.
AB  - In order to make rational decisions for further implementation of picture
      archiving and communication systems (PACS) in Viennese community hospitals, an
      assessment of the Sozialmedizinisches Zentrum Ost (SMZO) project was launched by
      the Viennese community hospital financing body. The aim of the technology
      assessment was to look at the experiences of day-to-day practice, organizational
      aspects of, and obstacles to developing the full potential of the PACS
      installation. The study analyzes the conditions for employment of digital
      radiology, gathers the experiences of national and international projects, and
      presents a view on critical points, from which options for further implementation
      can be derived. In the center of interest stood work organization, handling and
      user attitudes, perceptions of radiologists and clinicians, realism of
      expectations regarding economic efficiency, technical aspects, and influence of
      quality of medical care.

PMID- 9780542
TI  - Drugs for AIDS/HIV: assessing the evidence.
AB  - This article highlights factors that may cause bias in individual controlled
      trials or meta-analysis of zidovudine (AZT) in HIV disease. The overall benefit
      of AZT and antiretroviral drug combinations in the progression of HIV disease is
      probably greater than has been or can ever be shown in an ethical controlled
      trial.

PMID- 9780545
TI  - Report from the British Columbia Office of Health Technology Assessment (BCOHTA).
      Executive summary: does evidence support the selective use of bone mineral
      density testing in well women?

PMID- 9780544
TI  - Report from the Alberta Heritage Foundation for Medical Research. Evaluation of a
      telepsychiatry pilot project.

PMID- 9780546
TI  - Report from the Canadian Coordinating Office for Health Technology Assessment
      (CCOHTA). Leukoreduction: the techniques used, their effectiveness, and costs.

PMID- 9780547
TI  - Report from the Catalan Agency for Health Technology Assessment (CAHTA). Efficacy
      and safety of thrombolytic therapy in pulmonary thromboembolism.

PMID- 9780549
TI  - Reports from the Spanish Agency for Health Technology Assessment (AETS).

PMID- 9780550
TI  - [Changes in clinical intervention studies: when the wellbeing of the patients
      takes precedence].

PMID- 9780551
TI  - [Occupational exposure to lead in production units in Maracaibo, Venezuela].
AB  - A medical occupational study was performed in 40 workers belonging to productive
      units in telecommunication works, 22 to car radiator mechanics and 11 to battery
      repairs. A practical medical and occupational study was applied to the group and
      also were determined their blood lead and air lead exposure levels. Seventy-three
      individuals, without risk of laboral exposure to lead, without familiar,
      pathological and occupational antecedents, and healthy at the time of the test,
      to whom the blood lead levels were determined served as control group. The mean
      values of plumbemia in exposure workers to inorganic lead exceed the level
      threshold of the COVENIN 2277-85 norm (30 micrograms/dl) (Telecommunication work,
      40.10 micrograms/dl, radiators mechanics, 37.40 micrograms/dl and battery
      repairs, 45.77 micrograms/dl), values that were significantly higher (p < 0.0001)
      compared with the ones obtained in the non-exposed population. The factors that
      can influence the variability of the results were analyzed and it was established
      a correlation between the plumbemia of the radiator mechanics and battery
      repairmen and the length of occupational period and air lead levels (p < 0.0001).
      The inherent factors to the climatic, occupational and personal conditions of
      technicians in telecommunications, are presented as elements able to explain the
      lack of correlation between blood lead levels and length of occupational period
      and air lead. The clinical findings in exposed workers were unspecific. The
      workers do not practice or follow the basic sanitary regulations, personal
      protection and industrial security. This work will contribute to establish a
      basic description, to further and more complex observational prospective studies
      in order to determine the occurrence of alterations that are derived from
      occupational lead exposure.

PMID- 9780552
TI  - [Spirometry in workers in a wheat-processing industry].
AB  - In order to determine both clinical and spirometric changes due to high
      environmental concentrations of wheat dust at a wheat processing plant mill, 48
      exposed men and 48 age and antroprometrically-matched, non-exposed apparently
      healthy men were studied. In both groups a medical and occupational history were
      taken, and spirometric measurements were carried out, that included Forced Vital
      Capacity (FVC), Forced Expiratory Volume at the first second (FEV1), Peak Flow
      Rate (PFR), Forced Percentual Expiratory Volume (FEV%), Forced Percentual Vital
      Capacity (FVC%), Forced Expiratory Flow at 25% (FEV25%), at 50% (FEV50%) and at
      75% (FEV75%) of their Forced Vital Capacity, which were analyzed through Corzo's
      predictive equations and the lung deterioration's criteria by USA's Thoracic
      Association. The environmental wheat dust was determined by gravimetry and its
      concentration was higher than the legally admitted (3/5, 60%). There was a
      decrease in the PFR, FEV%, FEV25% and FEV75%. (p < 0.05). In addition, 4
      restrictive and 1 obstructive syndrome were detected in the exposed workers and
      none in the control group. The spirometric values diminished in a positive
      correlation with the time of exposure and smoking habits. There was no
      correlation between the clinical findings and the dust concentration but it did
      exist with the spirometric values. It is concluded that in this plant, the wheat
      dust exposed workers have a diminished spirometric values.

PMID- 9780553
TI  - [Ultrastructural aspects of lesions caused by Mycobacterium spp in AIDS].
AB  - Samples from necrotizing lesions in eight autopsy cases of AIDS were examined
      with transmission electron microscopy. They were selected among 35 autopsies of
      Mycobacterium spp infection and AIDS, and were part of a series of 230 autopsy
      cases of AIDS performed from 1984 to 1995 in the Anatomopathologic Institute at
      Central University of Venezuela. Ultrastructural aspects of micobacteriae, their
      relationship with macrophages and tissue alterations are discussed and related to
      the immune defcit observed in AIDS patients.

PMID- 9780554
TI  - [Primary Sjogren syndrome. Study of a population of patients at the Hospital
      Universitario de Caracas, Venezuela].
AB  - Sjogren's syndrome is an autoimmune exocrinopathy of unknown etiology. It is
      characterized by a chronic inflammatory process that leads to functional
      impairment and destruction of lachrymal and salivary glands. There is a primary
      and a secondary form of the disease; the latter accompanies a well defined
      connective tissue disease. As far as we know, there are no previous reports of
      primary Sjogren's syndrome in Venezuela. The main purpose of this study was to
      present the clinical findings and outcome of a population of patients diagnosed
      and followed in our hospital. A population of fifty-four patients predominantly
      females (96%) with a mean age of 42 (range 24 to 84) was studied. The presence of
      articular symptoms was the most common extraglandular manifestation (87%),
      followed by enlargement of parotideal glands (52%). Parotid enlargement and renal
      disease were observed with a higher frequency than previously reported in the
      literature. Recurrent enlargement of parotideal glands has been related to
      lymphoid malignant transformation in these patients. Our findings seem to suggest
      that the pattern of clinical expression of primary Sjogren's syndrome may be
      influenced by the genetic make-up of the population under study, and possibly by
      local environmental influences. Two of our cases developed pseudolymphoma, a
      transitional stage between the benign lymphoproliferation of primary Sjogren's
      syndrome and lymphoma. Furthermore, in this relatively small sample six patients
      have died during a short follow-up period, suggesting a potentially more
      aggressive course of the disease in our patients.

PMID- 9780555
TI  - [Vitamin K: biochemistry, function, and deficiency. Review].
AB  - Vitamin K is a cofactor for the synthesis of blood coagulation Factors II, VII,
      IX and X, and inhibitors such as Protein C and S and bone matrix protein. Its
      active form is a coenzyme in the glutamic acid carboxylation. Vitamin K-dependent
      factors form enzymatic complexes with calcium and membrane phospholipids. The
      insufficiency of gamma glutamic carboxylation impairs the hemostatic function.
      Hereditary deficiencies, antibiotics and oral anticoagulants, decrease the
      capacity of complex formation giving way to hemorrhage or thrombosis, or bone
      mass disturbances which are easily treated with administration of Vitamin K. The
      main causes of Vitamin K deficiency are lack of hepatic storage in newborns,
      liver insufficiency, malabsorption, dietetic deficiency, therapy with the
      antibiotics and coumarin administration. For the study of Vitamin K there are
      methods to measure the Vit K dependent proteins and as well methods to measure
      specifically the quinonas.

PMID- 9780556
TI  - [Prevalence of subgroups, serotypes, and electropherotypes of human rotavirus in
      Cumanaa, Venezuela].
AB  - From June 1992 to May 1993, rotaviruses were detected by an immunoenzymatic assay
      in 159 (49.5%) of 321 children admitted to the hospital with acute diarrhea. Of
      the 159 cases ELISA positive, 80 samples were chosen at random to investigate
      subgroups and serotypes of group A human rotavirus. By the ELISA test 9 (11.3%)
      of the strains were subgroup I, 46 (57.5%) were subgroup II, and 25 (31.3%) could
      not be grouped. The serotype G1 was identified in 52 cases (65%), G2 in 11 cases
      (13.8%), G3 in 1 case (1.2%), and 7 cases (8.8%) showed more than one serotype.
      By electrophoretic analysis of viral RNA, 137 (42.7%) of the samples exhibited an
      RNA pattern. The long pattern (59.1%) prevailed over the short pattern (35.8%),
      and by coelectrophoresis 8 different electropherotypes were found throughout the
      period of study. These results illustrate the great variety of rotavirus strains
      in this region of the country.

PMID- 9780557
TI  - Oesophageal carcinoma: difficulties in interpreting the role of combined modality
      therapy.

PMID- 9780558
TI  - A clinicopathological correlation of 134 stage 1 and 79 non-invasive cutaneous
      melanomas presenting over a decade (1984-1993) at the Mater Misericordiae
      Hospital, Dublin.
AB  - In a study of malignant melanoma during the period 1984-1993, 134 (63 per cent)
      had invasive melanoma and in 79 (37 per cent) melanoma was confined to the
      epidermis (in situ). There was female predominance, F: M = 2.4 : 1, a family
      history of melanoma in 1.5 per cent, a mean age at diagnosis of 50 yr. Females
      presented a decade earlier than males on average. Over half of invasive melanomas
      in females occurred on lower limbs; 40 per cent of lesions in males occurred on
      the trunk. Almost one third of lesions in males and over two thirds in females
      occurred in sun exposed area. Sixty per cent of invasive lesions were of the
      superficial spreading type and half of all lesions were histologically thin [less
      than 1.5 mm vertical depth]. Surprisingly, median lesion thickness was lower in
      males, probably reflecting the greater frequency of nodular lesions in females
      compared to males (36 per cent -v- 24 per cent). The marked increase in the
      number of invasive melanoma patients presenting in the second half of the decade
      studied (treble that of the first half) probably reflects an increase in melanoma
      incidence. Over the decade no change in invasive melanoma type, anatomical site
      or histological thickness was noted, the latter suggesting a failure to diagnose
      melanoma at an increasingly earlier stage. An official melanoma public education
      programme is required, particularly as half of the patients delayed 1 yr or more
      before seeking medical advice. However it is encouraging that, of the invasive
      melanomas, 30 per cent were small (< 10 mm), 50 per cent were histologically thin
      and that 37 per cent of all melanomas were in situ. The melanoma-in-situ group
      had a similar gender ratio and mean age at diagnosis to the invasive melanoma
      patients but lesions were smaller, were predominantly on the head, neck and limbs
      with lentigo melanoma as the commonest type.

PMID- 9780559
TI  - Open access gastroscopy--3 year experience of a new service.
AB  - We have audited the first 3 yr of a new open access gastroscopy service in the
      Royal Victoria Hospital, Belfast to assess service demands, patient demography
      and diagnostic trends. Over 3 yr there were 1872 referrals (800 from fundholding
      general practitioners), 8.8 per cent were non attenders and 5.4 per cent
      cancelled appointments. Endoscopic diagnostic categories showed no significant
      change over the 3 yr, 39 per cent non ulcer dyspepsia, 35 per cent gastro
      oesophageal reflux disease (GORD), 17 per cent peptic ulcer disease (PUD), 6 per
      cent GORD and PUD, 1 per cent gastric erosions and 0.8 per cent carcinoma.

PMID- 9780560
TI  - The current status of adjuvant hormonal therapy combined with radiation therapy
      for localised prostate cancer.
AB  - Analysis of the results of treatment of localised prostate cancer with radiation
      and surgery has identified patients who are at high risk of developing metastatic
      dissemination. High histologic grade, serum prostate specific antigen above 20
      ng/ml, extension beyond the capsule of the prostate, and involvement of lymph
      nodes are highly predictive of metastatic risk. Antiandrogen therapy has high
      rates of activity in the treatment of overt metastatic disease prompting its
      assessment as an adjuvant treatment added to radiation therapy. There are now
      major prospective randomized trials which have been completed. The current
      evidence indicates that a large survival benefit ensues when antiandrogen therapy
      is added to radiation for appropriately selected patients. This adjuvant approach
      is likely to become the standard of care. Strategies for further enhancement of
      adjuvant therapy are discussed.

PMID- 9780562
TI  - The accuracy of fine-needle aspiration biopsy in the diagnosis of head and neck
      masses.
AB  - Patients presenting with a mass in the head and neck region require a tissue
      biopsy in order to make a histological diagnosis. Fine needle aspiration (FNA)
      offers a safe, well tolerated and inexpensive method of obtaining such a biopsy.
      When the patient is first seen in the clinic, the FNA can be performed, the
      result read and appropriate management instituted. The results of FNA biopsies of
      head and neck masses performed between May 1993 and June 1995, at the Department
      of Otolaryngology, Head and Neck Surgery in Saint James's Hospital, Dublin were
      reviewed. Of the 130 patients who had FNA biopsies performed, 78 went on to have
      surgical excision of the mass. To determine the accuracy of FNA biopsy in the
      diagnosis of head and neck masses at our unit, we compared the cytology result
      and the final histology report of these 78 patients. The overall accuracy rate of
      FNA cytology was 95 per cent, when compared to the final histology result. The
      accuracy rate was 87 per cent for malignant lesions and 95 per cent for benign
      lesions. No complications were encountered in this study. Based on our results
      and those of other studies, we recommended performing FNA in all patients
      presenting with a mass in the head and neck region.

PMID- 9780561
TI  - Mother-to-child transmission of human immunodeficiency virus (HIV) in Ireland: a
      prospective study.
AB  - Symptomatic HIV infection was first diagnosed in an Irish child in 1985. A
      prospective study was initiated to determine the vertical transmission rate (VTR)
      of HIV and the average age of infant seroreversion and to monitor clinical,
      immunologic and virologic evidence for HIV infection in seroreverters. Ninety
      three HIV positive infants have been prospectively identified since 1985. The
      predominant underlying maternal risk factor for HIV infection is intravenous drug
      use (IVDU) (96 per cent). Of 93 infants, median gestational age was 40 weeks and
      median birth weight 3125 grams. Ninety-four per cent of infants were bottle fed.
      Currently 72 (77 per cent) infants are uninfected, 12 (13 per cent) are infected,
      4 (4.5 per cent) are indeterminate and 5 (5.5 per cent) have been lost to follow
      up. The intermediate estimate of vertical transmission rate (VTR) is 14.3 per
      cent. The median age at documented seroreversion was 12 months. There are no
      significant differences between infected and non-infected children in male/female
      ratio, gestational age, mode of delivery or birth weight. Strategies to reduce
      the transmission of HIV among drug users in combination with routine antenatal
      screening and antiretroviral prophylaxis of vertical transmission are all
      measures which can reduce HIV infection in our children.

PMID- 9780563
TI  - Rapid serological diagnosis of Helicobacter pylori: a need for caution and re
      evaluation.
AB  - Screening for Helicobacter pylori in dyspeptic patients may improve selectivity
      for gastroscopy. Rapid serological tests based on ELISA technique are cheap,
      readily available and simple to use in the clinical setting. However local
      evaluation is essential in order to validate these techniques. Fifty-six
      dyspeptic patients (aged less than 45 yr) had a rapid serological test (Helisal)
      performed prior to gastroscopy. At gastroscopy H. pylori status was assessed
      using culture and histology. The Helisal sensitivity was 80 per cent, specificity
      82 per cent. Screening patients with the Helisal test would have missed 6
      patients with peptic ulcer disease and 2 with oesophagitis. The Helisal test did
      not perform satisfactorily as a screening test in selection of patients for
      gastroscopy.

PMID- 9780564
TI  - In-vitro activity of piperacillin/tazobactam relative to other antibiotics
      against blood culture isolates.
AB  - Resistance of bacteria to antibiotics is an increasing problem in many countries.
      Accurate locally relevant information is essential for detection and control of
      emerging resistance and to facilitate choice of empirical antibiotic therapy in
      the immediate management of seriously ill patients. We have determined the
      minimum inhibitory concentration of piperacillin/tazobactam for 97 strains of
      bacteria (55 Enterobacteriaceae, 13 non-fermentative Gram-negative bacilli, 22
      Staphylococcus aureus, 6 Enterococcus faecalis and 1 Bacillus cereus) isolated
      from blood cultures and compared its activity to that of amoxycillin, co
      amoxiclav, cephalothin, cefotaxime, ceftazidime, ciprofloxacin, gentamicin,
      piperacillin, cefotaxime. The strains were consecutive non-fastidious isolates
      with the following qualifications: coagulase negative staphylococci and
      diphtheroids were excluded and the number of Staphylococcus aureus isolates was
      limited to 12 methicillin-resistant and 10 methicillin-sensitive strains.
      Multiple isolates of the same species from individual patients were not included.
      The minimum inhibition concentrations of methicillin, penicillin, teichoplanin
      and vancomycin were also determined for specific groups of organisms. MICs were
      determined by the Etest method (AB Biodisk, Solna, Sweden) on Mueller Hinton
      agar. The MICs of appropriate American Type Culture Collection control strains
      were determined. Based on the interpretative criteria of the National Committee
      for Clinical Laboratory Standards (USA), 87 per cent of Gram-negative bacilli
      were susceptible to piperacillin/tazobactam compared with amoxycillin 26 per
      cent, cephalothin 35 per cent, co-amoxiclav 54 per cent, piperacillin 56 per
      cent, cefotaxime 69 per cent, ceftazidime 84 per cent, gentamicin 85 per cent and
      ciprofloxacin 91 per cent. Of all isolates 75 per cent were sensitive to
      piperacillin/tazobactam, compared with amoxycillin 22 per cent, cephalothin 35
      per cent, piperacillin 41 per cent, co-amoxiclav 52 per cent, cefotaxime 59 per
      cent, ceftazidime 60 per cent, gentamicin 74 per cent and ciprofloxacin 77 per
      cent. Two isolates (1 E. coli and 1 Klebsiella pneumoniae) with antibiograms
      consistent with the relatively new resistance phenomenon of extended spectrum
      beta-lactamase production were identified. The spectrum of activity of
      piperacillin-tazobactam for empirical antibiotic therapy is significantly greater
      than that of piperacillin alone and is similar to that of ciprofloxacin and
      gentamicin.

PMID- 9780565
TI  - Instructions for ambulatory surgery--patient comprehension and compliance.
AB  - Ambulatory surgery has proliferated as a result of increasing inpatient costs.
      Its high level of safety has resulted in its extension to less healthy, often
      elderly patients. Patient compliance with instructions is essential to avoid
      morbidity. We aimed to identify subgroups potentially at risk due to non
      compliance. A confidential questionnaire was administered to 220 consecutive
      daycase patients. Data included: patient demographics, duration of fasting,
      taking of medications that morning, importance of fasting and medication
      instructions, mode of post-discharge transport, and whether they had someone to
      stay with them that night. Seven (3.5 per cent) patients admitted to non
      compliance with fasting instructions, with 8 per cent considering these
      instructions non-essential. Thirteen of 59 patients on medications took them
      against instructions, with 9 patients considering the instructions non-essential.
      Eight patients admitted intending to drive home; 7 per cent admitted to having no
      one to stay with them on the night of surgery. A significantly minority of
      patients (particularly male) admit to non-compliance with ambulatory surgery
      instructions; these figures may be underestimates. Absence of anaesthetic/medical
      input and lack of reinforcement probably contribute to non-compliance. Some
      medication-related non-compliance may be appropriate (e.g. antianginals,
      antihypertensives) and may reflect conflicting instructions given to the patient.
      The stopping of all medications prior to ambulatory surgery needs revision. Older
      patients living alone may not be suitable candidates for ambulatory anaesthesia.

PMID- 9780566
TI  - Psychiatric morbidity in breast cancer--a review.

PMID- 9780567
TI  - Psychiatric morbidity following the diagnosis and treatment of early breast
      cancer.
AB  - Psychiatric illness associated with breast cancer still goes unrecognised and
      untreated. A prospective study was carried out on a consecutive series of 33
      patients with early breast cancer. Patients were interviewed following their
      diagnosis and 3 to 6 months post-mastectomy. Patients also completed the General
      Health Questionnaire 60 (GHQ 60) and the Leeds Scales for the Self-Assessment of
      Anxiety and Depression. Seven patients suffered from a depressive disorder at the
      post-operative interview. One patient suffered from an anxiety disorder. One of
      the depressed patients had received antidepressant medication from her general
      practitioner. The GHQ 60 was able to predict depressive illness in the post
      operative period with a sensitivity of 71 per cent at the pre-operative
      diagnostic stage. This study is consistent in its findings of increased
      psychiatric morbidity in early breast cancer patients in the months after
      surgery. It also highlights the usefulness of a self assessment questionnaire in
      predicting it.

PMID- 9780568
TI  - In Haughton's footsteps: mathematical insights into bioengineering and
      rehabilitation.
AB  - Four attempts are outlined which the author has made to develop mathematical
      models for topics encountered in bioengineering and rehabilitation. The first is
      autoregulation in the kidney, for which a nonlinear oscillator model is derived,
      based on observations of flow noise made by Erol Basar. The second is a nonlinear
      observer based on the theory of automatic control, developed to study patterns of
      spastic torque in paralysed legs via the pendulum test. The third is a design
      study of a skeletal muscle reflex arc involving the muscle spindle dynamics and
      invoking a principle of optimum stability. The final topic is an attempt to lay
      the groundwork for a mathematical theory of the cross-bridge or sliding filament
      mechanism of muscular contraction.

PMID- 9780569
TI  - Prolonged noxious stimulation increases periaqueductal gray NMDA mRNA expression:
      a hybridization study using two different rat models for nociception.
AB  - The density and distribution of N-methyl-D-aspartate receptor (NMDAR1) mRNA
      expression in the rat midbrain Periaqueductal gray (PAG) following exposure to
      unilateral peripheral inflammation or chronic constrictive injury (CCI) as models
      for chronic peripheral nociception were examined using the in situ hybridization
      technique. The NMDAR1 hybridization signal intensities increased significantly in
      the ventrolateral areas of the caudal and middle thirds of the PAG after 3 days
      of Complete Freund's Adjuvant (CFA) injection. Likewise, rats subjected to CCI
      showed significant increases in hybridization signal intensities in comparison to
      sham operated animals in both the ipsi and contra-lateral ventrolateral quadrants
      of the caudal and middle thirds of the PAG. In the caudal dorsal raphe, the CFA
      and the CCI treated animals showed a significant increase in signal hybridization
      compared to control and sham operated groups while the rostral dorsal raphe
      showed no significant changes in either CCI or CFA treated groups. In contrast,
      there was no significant change in signal intensity of NMDAR1 mRNA in the dorsal
      subdivisions of the PAG following either CCI or CFA treatment. These results
      demonstrate significant bilateral increase in NMDAR1 mRNA expression in the
      ventrolateral areas of the caudal and middle thirds of the PAG and the caudal
      half of the dorsal raphe following chronic nociception. The up-regulation
      phenomenon may constitute a reactive mechanism against chronic neuropathic pain
      in the PAG.

PMID- 9780571
TI  - Vascular complication of anterior dislocation of shoulder with associated
      brachial plexus injury--a case report.

PMID- 9780570
TI  - High attenuation gyri CT in postasphyxial encephalopathy.
AB  - Two term infants suffering severe asphyxial events were found to have diffusely
      high attenuation of the cortical gyri on CT scanning within 12 days. The findings
      are consistent with haemorrhagic necrosis or microcalcification. This feature has
      rarely been described in the literature. The evolution of the CT appearance, the
      possible neuropathological findings and the relationship with hypoxic-ischaemic
      encephalopathy are discussed.

PMID- 9780572
TI  - Lessons from eugenics for the neoeugenic era.

PMID- 9780574
TI  - Ethics and genetic testing.

PMID- 9780573
TI  - Eugenics in the south: the Carrie Buck case.

PMID- 9780575
TI  - Ethical issues in cloning and embryo research.

PMID- 9780576
TI  - Gene therapy: ethical and social issues.

PMID- 9780577
TI  - Enhancement technology, ethics, and public policy.

PMID- 9780578
TI  - Some reasons to be concerned about genetic enhancements.

PMID- 9780579
TI  - [Risk factors for clinical prognosis in bacterial meningitis beyond the neonatal
      period].
AB  - A retrospective clinical study of 64 cases with bacterial meningitis beyond the
      neonatal period in the department of pediatrics of St. Mary's Hospital (1985
      1995) was conducted. Haemophilus influenzae (H. influenzae) (28 cases, 43.8%) and
      Streptococcus pneumoniae (S. pneumoniae) (23 cases, 35.9%) were common pathogens.
      The prognosis was classified into three groups; normal (42 cases, 65.6%),
      neurological sequelae (17 cases, 26.6%) and death (5 cases, 7.8%). We analyzed
      the risk factors associated with their outcome. The body temperature at
      admission, platelet count, CSF examination (WBC, glucose, GOT, GPT) were
      prognostic factors. The prognosis of bacterial meningitis caused by S. pneumoniae
      was worse than those due to H. influenzae (p = 0.0347).

PMID- 9780580
TI  - [A study of virulence factors produced by MRSA strains isolated from blood
      samples].
AB  - Toxic shock syndrome toxin-1 (TSST-1) and enterotoxins are important virulence
      factors produced by Staphylococcus aureus. It is reported that these toxins are
      associated with septic shock and toxic shock syndrome. We investigated the toxin
      production and coagulase types of 701 MRSA strains isolated in Sasebo City
      General Hospital between 1994 and 1996 TSST-1 or/and enterotoxins were detected
      in 67% of all MRSA strains, and those were detected in 88% of MRSA strains
      isolated from blood samples. 45% of all MRSA strains produced both TSST-1 and
      enterotoxin C, and 70% of MRSA strains obtained from blood produced those toxins.
      Frequency of TSST-1 or/and enterotoxin production by MRSA strains isolated from
      blood samples was significantly higher than that by MRSA strains isolated from
      urine and pharynx (p < 0.05), and frequency of both TSST-1 and enterotoxin C
      production by MRSA isolates from blood was significantly higher than that by MRSA
      strains isolated from pharyngeal sample (p < 0.05). This study indicated that
      investigation of virulence factors produced by MRSA might give the useful
      information on prevention and treatment of MRSA infection.

PMID- 9780581
TI  - [An outbreak caused by hepatitis A virus in an institution for the mentally
      handicapped--detection of hepatitis A virus RNA using CTAB method].
AB  - The prevalence of hepatitis A virus (HAV) antibody in people has decreased from
      year to year in Japan. A sequential outbreak occurred in an institution for the
      mentally handicapped people in Chiba City in the summer of 1995. Eight people
      were infected including 7 residents and one staff member. We tested to detect
      antigen in fecal samples by ELISA and PCR for early diagnosis for hepatitis A
      infection. Four sera and 5 feces were obtained from 5 patients between 2 and 8
      days after the onset of symptoms. The anti-HAV IgM was found to be positive in 4
      sera examined. The HAV antigen was detected in 3 out of 5 feces using ELISA. An
      existence of inhibitor in 2 negative specimens against the ELISA was suggested by
      the recovery test of added antigen. HAV RNA was extracted by CTAB method from
      feces and detected in 4 our of 5 specimens in PCR amplification and in all of 5
      specimens in nested PCR amplification. The sequence of PCR products in the P1/P2
      junction of the HAV genome revealed that the virus associated with the outbreak
      belongs to HAV subgenotype IA. HAV RNA was detected in ELISA negative specimens
      and in the specimen from a patient 2 days after the onset of symptoms using PCR
      amplification by CTAB method. These results indicate that PCR amplification was
      useful for the early diagnosis of hepatitis A infection.

PMID- 9780582
TI  - [Determination of anti-Bartonella henselae antibody by indirect fluorescence
      antibody test--comparison of two types of antigen: non-cocultivated B. henselae
      and cocultivated B. henselae with Vero cells].
AB  - Serum anti-Bartonella henselae IgG and IgM antibody titers for the diagnosis of
      cat scratch disease (CSD) were determined by indirect fluorescence antibody (IFA)
      tests. B. henselae as antigen were harvested either by cocultivating with Vero
      cells (cocultivated B. henselae) or by cultivating without them (non-cocultivated
      B. henselae). Based on the results on 110 healthy adults, cut off values were set
      at 1:32 for IgG, and < 1:20 for IgM antibodies. According to these criteria, IgG
      antibody was positive in 2.7% of the 110 adults, while nobody was positive for
      IgM antibody. The titers did not change depending on the types of antigen used.
      On the other hand, IgG antibody titers against cocultivated B. henselae tended to
      be higher than those against non-cocultivated B. henselae in 33 CSD suspected
      patients; 75.8% of the patients were anti-B. henselae IgG positive when tested
      with cocultivated B. henselae as antigen, while only 48.5% of the same patients
      gave positive results with non-cocultivated B. henselae. Anti-B. henselae IgM
      antibody was positive in 24.2% of the 33 CSD suspected patients against both
      types antigen. Vero cells themselves seemed to nonspecifically bind some IgM (but
      not IgG). We recommended cocultivated B. henselae as antigen for IgG IFA, and non
      cocultivated B. henselae for IgM IFA in the serological tests of CSD.

PMID- 9780583
TI  - [Anti-verotoxin-neutralizing antibody in intravenous gammaglobulin preparations].
AB  - Intravenously administered immune globulin therapy has been reported to be an
      effective treatment for serious patients with verotoxin-producing Escherichia
      coli infections while an efficacy for VT2 are under discussion. We therefore
      examined in vitro commercially available immune globulin preparations for the
      presence of anti-VT neutralizing antibodies in expectation of protecting a
      patient from serious complications as HUS. We examined 47 lots of gamma-globulin
      prepared by 5 pharmaceutical companies in Japan. Of them 29 lots were prepared
      from imported blood and 18 lots were from Japanese donors' blood. They were
      prepared in each company following their own manufactures' process. Neutralizing
      activity for VT1 and VT2 were determined by means of cytotoxicity using ACHN
      (renal adenocarcinoma, human) cells. All lots of gamma-globulin preparations from
      imported blood completely neutralized 125 pg/ml VT1 at the concentration of 12.5
      mg/ml, and no significant difference was found in the manufactures' process. On
      the other hand gamma-globulin preparations from Japanese donors' blood
      neutralized VT1 five times less than the former. None of all preparations
      neutralized VT2. Gammaglobulin preparations were produced from pooled human
      plasma. To know the difference of neutralizing activities in the source, we
      examined randomly selected 239 human plasma samples of which 51 were from
      Japanese donors' blood and 188 were from imported blood. Prevalences of
      neutralizing activity of VT1 in imported plasma and domestic plasma were 10.6%
      and 2.0%, respectively. The prevalence of neutralizing antibody in these plasma
      samples reflects the different neutralizing activity of VT1 in gamma-globulin
      preparations prepared from imported blood and Japanese donors' blood. From these
      results, by selecting the lot of gamma-globulin preparations or the material of
      plasma with highly neutralizing activity, intravenously administered immune
      globulin therapy may be effective for VT1. The lack of VT2-neutralizing activity
      in any gamma-globulin preparation promotes us to develop humanized anti-VT2
      monoclonal antibody for the prevention of HUS in high risk children.

PMID- 9780584
TI  - [Antifungal susceptibility of clinically isolated Candida albicans by broth
      microdilution method].
AB  - In this study we investigated the antifungal susceptibility of 285 strains of
      Candida albicans isolates at Kinki University Hospital from March 1995 to
      December 1996. The antifungal agents tested were fluconazole, miconazole,
      intraconazole, amphotericin B and flucytosine. The susceptibility testing were
      performed according to the broth microdilution method standardized by National
      Committee for Clinical Laboratory Standards (M27-T). Most isolates of C. albicans
      showed relatively a low MIC value and the MIC90S were calculated at 1
      microgram/ml; fluconazole, 0.125 microgram/mg; miconazole, 0.06 microgram/ml;
      itraconazole, 1 microgram/ml; amphotericin B, 0.25 microgram/ml; flucytosine.
      There was only one strain that showed high resistance against fluconazole and it
      showed cross-resistance against miconazole and itraconazole. There were two
      flucytosine resistant strains. The MICs of amphotericin B were tightly clustered
      and resistant strain were not observed.

PMID- 9780585
TI  - [A clinical investigation of bacteremia for the past ten years at the Second
      Department of Internal Medicine, Jikei University Hospital].
AB  - We clinically investigated a total of 288 cases of bacteremia for the past ten
      years, from January 1986 to December 1995, at the Second Department of Internal
      Medicine in the jikei University Hospital. All of the subjects who had a positive
      reaction to blood culture or catheter tip culture were investigated for their
      basic disease, complications, and detected bacteria. Malignant tumors, chronic
      renal failure, diabetes mellitus, and hematologic disease were frequent by noted.
      The cases due to primary infection were mainly respiratory organ infection or
      urinary tract infection, which were 47.8% of the total. In 31.3% of the total,
      catheter tip cultures were positive. Except for catheter related infection, Gram
      positive coccus were detected in 40.3%, which was most frequent. Methicillin
      resistant Staphylococcus aureus (MRSA) were 8.1% and Staphylococcus epidermidis
      were 11.2%. In catheter related infection, Gram-positive coccus were detected in
      59.9%, which was most frequent amongst them, MRSA was 17.2%, S. epidermidis was
      16.2%. The mortality of bacteremia was 12.5%, mainly from hematologic diseases,
      immunodeficiency due to long term steroid administration etc. Accordingly, the
      more the advance of chemotherapy, the better the prognosis of septicemia is.
      Appearance of catheter related infection was unexpected frequent. Increase of
      immunocompromised host is thought to be one of the main factors in the outbreak
      of bacteremia.

PMID- 9780586
TI  - [Evaluation of a rapid enzyme immunoassay membrane test for diagnosis of
      influenza A virus infection].
AB  - A rapid enzyme immunoassay membrane test, Directigen Flu A (Becton Dickinson,
      USA), was evaluated by using virus isolates and clinical specimens. The reference
      laboratory diagnosis was based on the results of virus isolation. Directigen Flu
      A was reactive for all subtypes of human influenza A viruses, including reference
      strains of H1N1, H2N2 and H3N2. Moreover, H5N1 (Hongkong/156/97) was also
      detected by this kit. No cross reactivity was detected with other respiratory
      viruses. Directigen Flu A showed positive reaction with the solution containing
      influenza A virus of 2.4 x 10(3) pfu/assay. The rapid test demonstrated 77.9%
      sensitivity and 98.4% specificity for testing of throat swabs from children with
      respiratory symptoms. It showed higher sensitivity and specificity (92.1% and
      100%) for testing of nasopharyngeal aspirates. Directigen Flu A should be useful
      for the rapid diagnosis of influenza A virus infection.

PMID- 9780587
TI  - [Evaluation of immunochromatography-based rapid detection kit for fecal
      Escherichia coli O157].
AB  - "Quix" is an immunochromatography-based direct detection kit for the E. coli O157
      LPS antigen in the patient's stool. The present study was conducted to evaluate
      the efficacy of the kit for rapid diagnosis of enterohemorrhagic Escherichia coli
      (EHEC) O157 infection. Sensitivity of the kit was determined using a pure culture
      of a clinical isolate of E. coli O157. Analytical sensitivity was found to be 5 x
      10(5) CFU/ml. When compared with the culture method using fecal samples of 64
      patients and with bloody diarrhea, sensitivity and specificity were 95.0% (19/20)
      and 86.4% (38/44), respectively, and overall agreement to culture method was
      89.1% (57/64). One patient was found positive by culture method while negative in
      the present method, where the sample contained a low number of the cells less
      than the detection limit. Four of the six patients with a negative result by
      culture method and positive in the present method, were confirmed E. coli O157
      infection by positive IgM antibody response against the E. coli O157 LPS. The
      discrepancy between the two methods seemed to be attributable to antibiotic
      administration. In one patient, Salmonella urbana (O30(1)30(2)) was detected. The
      O30(1) antigen of this bacterium is well known to be identical to the E. coli
      O157 antigen. When the present method was compared with an ELISA-based E. coli
      O157 LPS antigen detection kit, sensitivity and specificity were 100% (11/11) and
      82.1% (23/28), and overall agreement to ELISA method was 87.2% (34/39). From
      these findings, Quix is useful as a rapid diagnostic kit in the primary clinics,
      outpatient or bedside use. E. coli O157 LPS antigen in patient's fecal samples
      can be detected in about five minutes with this simple procedure. Early diagnosis
      using such a simple kit will largely contribute for the early treatment and
      prevention of severe complications of the E. coli O157 infection.

PMID- 9780588
TI  - [Use of amantadine for influenza A encephalopathy].
AB  - Recent experience in Japan has suggested that influenza A encephalopathy may
      occur more frequently than generally appreciated and may have a grave prognosis.
      Influenza A encephalopathy has been managed to date only with supportive
      measures, because the efficacy of anti-viral therapy for encephalopathy has not
      efficacy of anti-viral therapy for encephalopathy has not yet been documented.
      During the period from January 1996 to February 1998, we treated two cases of
      influenza A encephalopathy with amantadine (6 mg/kg/day, p.o., for 7 days). Both
      became status epileptics and had loss of consciousness within 24 hours after the
      onset of illness. They recovered without sequelae and had no side effects from
      amantadine treatment. Amantadine may be useful in the treatment of influenza A
      encephalopathy.

PMID- 9780589
TI  - [Serratia marcescens brain abscess in a newborn].
AB  - The patient was born by emergency cesarean section for fetal distress at 35 weeks
      gestation with a weight of 2740 g. The early neonatal course was complicated by
      transient tachypnea and renal failure. He was receiving oxygen and diureticus in
      incubator for 5 days and his condition was very improved on day 5. On day 7 he
      became lethargy and there was inability to tolerate feeding. Investigation of the
      cerebrospinal fluid revealed 8,000 leukocytes/microliter. S. marcescens was grown
      from cultures of both blood and cerebrospinal fluid. Treatment was started with
      cefotaxime and ampicillin every 6 hour. On day 14 the CT showed a brain abscess
      located parietooccipitally on the left side and diffuse infarction on the right
      side. On day 14 and 23 recurrence of increased leukocytes in the cerebrospinal
      fluid, high values of serum CRP and deterioration of clinical symptoms were
      observed. It is thought that the episodes show rupture of the abscess into the
      lateral ventricle. On day 55 surgical drainage was performed for the
      hydrocephalus. On day 110 the abscess was not found in the brain CT scan. His
      psychomotor development 3 years later was equivalent to two years old and he had
      secondary epilepsy.

PMID- 9780590
TI  - [A case of the active intestinal tuberculosis detected during the examination of
      the right pleural effusion].
AB  - A 76-year-old female was admitted to our hospital because of fever and the right
      pleural effusion. On the analysis of pleural effusion, the total cell count was
      6720/microliter with 95% lymphocytes, and ADA was 38.1 U/l. The culture of
      pleural effusion was negative, and the smear and PCR for Mycobacterium were also
      negative. For examinations, we performed eterography that showed cicatricial
      strictures of intestine. X-ray examination of the colonated colonoscopy showed
      ulcers (circular type), shortening of the colon, Bauhin's value insufficiency and
      diverticulum-like deformity. Then, she was diagnosed as intestinal tuberculosis.
      The smear and PCR of biopsy specimens from the lesion were positive, and
      antituberculotic therapy was effective. Finally, the culture of pleural effusion
      for Mycobacterium tuberculosis was positive after 8 weeks. We thought intestinal
      examination may be useful for the diagnosis of tuberculosis, when lymphocyte-rich
      exudative pleural effusion of unknown etiology is seen.

PMID- 9780591
TI  - [Comparison of selective screening of verotoxin-producing Escherichia coli (VTEC)
      isolation depending on O-serotyping and hemolysis from faeces of healthy
      persons].

PMID- 9780592
TI  - [An agranulocytic case with Aspergillus diffuse external otitis cured by
      amphotericin B topic administration].

PMID- 9780593
TI  - [Community-acquired pneumonia by Streptoccoccus pneumoniae in community
      hospital].

PMID- 9780594
TI  - HLA DQA1 genotyping of Chinese in Taiwan by PCR-RFLP.
AB  - Population data were established for the HLA DQA1 locus among 147 Chinese in
      Taiwan by the PCR-RFLP flowchart system. Twelve alleles could be differentiated
      in this study, although only nine alleles were found among the above samples.
      There were no discrepancies in the results obtained by PCR-RFLP when compared to
      the results obtained by the AmpliType HLA DQ alpha typing kit. Using the Chi
      square test, significant differences were observed (p < 0.005) between this data
      and that for Japanese, African Americans and US Caucasians. The observed
      heterozygosity was 83% with a discrimination power of 0.93.

PMID- 9780595
TI  - The role of CD8+ cells and CD11a in the rejection-reaction of the allogeneic
      microskin grafting.
AB  - By using histological tissue sections and immunohistochemical stains, the
      rejection-reaction of the allogeneic microskin grafting of rabbit-skin wounds was
      studied. The results revealed that the rejection started early in the days
      following transplantation. In the second week following transplantation, severe
      graft rejection with epithelial destruction was noted. In addition, an increase
      of CD8+ cells and expression of the adhesion molecule-CD11a-were also noticed and
      persisted throughout the days following transplantation. These findings suggest
      that the CD8+ cells and CD11a may play a major role in the rejection of
      allogeneic skin grafting.

PMID- 9780596
TI  - In vitro effects of various neuropharmacological agents on the motility of adult
      Clonorchis sinensis.
AB  - Stimulatory effects were observed in vitro when 5-HT was applied to whole worm
      preparations of Clonorchis sinensis. The stimulatory action of 5-HT was
      antagonized by tryptophol, clomipramine and imipramine. Strychnine remarkably
      stimulated motility. The action of strychnine was enhanced by 5-HT but inhibited
      by tryptophol. GABA, Phenylephrine, isoproterenol, dibenamine and phentolamine
      showed little influence on motility. Inhibitory effects were caused by eserine,
      arecoline, carbachol, DMPP and hemicholinium-3, but not by ACh, pilocarpine and
      McN-A-343. The inhibitory actions of eserine or carbachol were not antagonized by
      d-tubocurarine, hexamethonium or atropine. These results suggest that in
      regulating the motility of C. sinensis ACh may function as an inhibitory
      neurotransmitter and 5-HT as an excitatory transmitter in a manner similar to
      that already established for other trematodes such as Fasciola hepatica and
      Schistosoma mansoni.

PMID- 9780597
TI  - Injection pain with propofol: the effectiveness of thiopentone on induction.
AB  - One hundred and twenty-seven children aged 3-6 years were allocated to four
      groups. All of them received venous cannulation on the dorsum of the hand. On
      induction, the group L1, L2 and L3 patients received propofol 3 mg/kg mixed with
      lignocaine 0.15 mg/kg, 0.3 mg/kg, 0.6 mg/kg, respectively. The group T patients
      received thiopentone 3 mg/kg, then propofol 1.5 mg/kg mixed with lignocaine 0.075
      mg/kg. Pain on injection was categorized into two-assessment items (facial
      expression and limbs withdrawal). The facial expression category were subdivided
      into none, mild (knit of brows), moderate (grimace), and severe (crying). The
      withdrawal of limbs was categorized into none, mild (withdrawal of hand),
      moderate (withdrawal of fore-arm and arm), severe (withdrawal of arm and twisting
      of body). Patients were monitored using an electrocardiogram, pulse oximeter,
      autonomic noninvasive blood pressure measuring device and capnography. The
      patient characteristics did not differ significantly among the four groups. Pain
      on injection was significantly more frequent in the group L1 patients (81%)
      compared with the group T (27%) patients. Increasing lignocaine dose reduced the
      incidence of pain graded as "moderate" or "severe" though there was no
      significant difference. The incidences of excitatory effect on propofol injection
      were reduced with increasing lignocaine dose and prior administration of
      thiopentone but there were no obviously differences among groups. We concluded
      that thiopentone reduced injection pain on propofol and should be recommended.

PMID- 9780598
TI  - Clinical study of failure in continuous spinal anesthesia with bupivacaine.
AB  - BACKGROUND: Continuous spinal anesthesia (CSA) has been considered to be better
      in temporal and dose flexibility, as well as hemodynamic stability than single
      dose spinal anesthesia. However, the failure of spinal anesthesia is not a rare
      experience for anesthesiologists. Here we present our experience in solving the
      problem and discuss the possible causes for the failure. METHODS: 236 cases were
      studied retrospectively from January to December in 1996. All were over 65 years
      old, ASA III, scheduled for transurethral procedures or orthopedic operation. CSA
      was performed with 0.2% bupivacaine. Failed CSA was confirmed by positive pin
      prick test at T10 dermatome(umbilicus) 30 minutes after 20 mg bupivacaine was
      injected. For failed cases, 5 mL 1% lidocaine was injected intrathecally for
      rescue. The failure rate, sensory and motor blockade, success rate by changing to
      lidocaine and its dosage were recorded. RESULTS: Eleven of 236 cases (4.7%) were
      considered spinal failure since the initial 20 mg bupivacaine could not provide
      adequate T10 anesthesia in 30 minutes. Addition of 5 mL 1% lidocaine produced a
      profound sensory and motor blockade in 9 cases, while further lidocaine injection
      was required in two cases. The success rate by rescuing lidocaine was 100% with
      an average lidocaine consumption by 52.5 +/- 4.5 mg. DISCUSSION: Factors
      contributed to failure spinal anesthesia including failure of technique, errors
      of judgment, maldistribution and failure of local anesthetic itself. However, we
      thought that change of pH value of local anesthetic in CSF may play a great part
      in these failed CSAs. Despite the reasons for failure, we demonstrate that
      failure of continuous spinal anesthesia by 0.2% bupivacaine can be readily
      resolved by 1% lidocaine.

PMID- 9780599
TI  - Partial sensory rhizotomy as an alternative treatment of trigeminal neuralgia.
AB  - Microvascular decompression is a well established technique in the treatment of
      medically refractory trigeminal neuralgia when a significant vascular contact is
      identified during posterior fossa exploration. However, in patients with
      recurrent trigeminal neuralgia after this type of surgery or if no significant
      vascular indentation is found during surgery, a partial sensory rhizotomy is
      often the preferred alternative mode of treatment. For eight such patients,
      partial sensory trigeminal rhizotomy was performed with the involved
      distribution. Two patients were cases of previous failure, while the other six
      cases showed a lack of vascular indentation during operation. All the patient
      underwent microvascular decompression in addition to partial sensory trigeminal
      rhizotomy with dissector disruption. Sensory examination was performed during the
      outpatient department follow-up. In these eight such patients, five had excellent
      results, two continued to have mild pain that was well controlled with
      carbamazepine, and one had poor results. The mean follow-up period was 58 months.
      Our study indicates that sensory loss is compatible with the extent of nerve
      section and that touch loss is less evidence than sensory loss. Partial sensory
      trigeminal rhizotomy is recommended as the alternative treatment strategy of
      choice for patients with trigeminal neuralgia who lack significant vascular
      contact during operation.

PMID- 9780600
TI  - Surgical treatment of intracranial meningiomas in geriatric patients.
AB  - We studied retrospectively a series of 36 patients who underwent the surgical
      removal of an intracranial meningioma between April, 1982 and April, 1997. Their
      ages ranged from 65 to 78 years (mean age: 70.2 years); 27 patients were female,
      and 9 were male. Thirteen (36.1%) were located at the convexity, 6(16.7%) at the
      falx/parasagittal area, and 16(44.4%) at the skull base, tentorium, and posterior
      fossa. Operative mortality was 11.1%, but the rate was increased to 16.7% at 3
      months follow-up. It was significantly higher than the younger age group (p <
      0.05). Postoperative complications were manifested in 17 of 36 patients (47.2%).
      The postoperative morbidity rate was significantly higher in patients with class
      III of ASA physical status (American Society of Anesthesiology classification).
      Twenty-three (63.9%) patients had good postoperative outcome (Karnofsky rating
      scale of 80 or more). Various prognostic factors were evaluated, the most
      important of which were preoperative general health condition and neurological
      status. Age per se is not a contraindication to the surgery of intracranial
      meningiomas in the elderly patient.

PMID- 9780601
TI  - Magnetic resonance images of neuronal migration anomalies.
AB  - Neuronal migration anomalies are a spectrum of brain malformations caused by
      insults to migrating neuroblasts during the sixth week to fifth month of
      gestation. To study the characteristics of MRI findings in migration anomalies,
      MR images of 36 patients (28 children and 8 adults) with migration anomalies were
      evaluated. Five patients had lissencephaly, eight had pachygyria, twelve had
      schizencephaly, six had heterotopias of gray matter, three had
      hemimegalencephaly, and two had polymicrogyria. The frequency of migration
      anomalies was 0.51% of all cranial MRI studies and 1.21% of pediatric cranial MRI
      studies at our hospital. The major clinical presentations of these patients were
      seizure (64%), development delay (42%), motor deficits (42%) and mental
      retardation (25%). Twenty-five patients (69%) associated with other brain
      anomalies, including: other migration anomalies in 12 cases (33%), absence of the
      septum pellucidum in 10 cases (28%), Dandy-Walker malformation/variant in 5
      cases, arachnoid cyst in 4 cases, agenesis of the corpus callosum in 3 cases,
      holoprosencephaly in 2 cases, mega cisterna magna in 1 case and cephalocele in 1
      case. Some of them presented with multiple complicated anomalies. As MR imaging
      provides superb gray-white matter distinction, details of cortical anatomy and
      multiplanar capability, it can clearly delineate the detail morphologic changes
      of the brain caused by neuronal migration disorders as well as the associated
      anomalies.

PMID- 9780602
TI  - Contralateral recurrent cerebellar hemangioblastoma--a case report.
AB  - Hemangioblastomas are regarded as benign neoplasms. They may recur in 3 to 10% of
      cases after apparently total excision. The opposite site recurrence is not found
      in the reported literature. A case is described in which, after successful
      removal of a cerebellar hemangioblastoma followed by two years of freedom from
      symptoms, developed a new growth of cerebellar hemangioblastoma contralaterally
      again. The histology of the tumor tissue is in no way different from that of a
      conventional hemangioblastoma. This case gives us some insights into the
      biological multipotentiality of cerebellar hemangioblastoma. We stress that close
      observation is absolutely necessary for this unique group of tumors, even after
      total removal.

PMID- 9780603
TI  - Sensorineural hearing loss in MELAS syndrome--case report.
AB  - A mitochondrial tRNA mutation at nucleotide 3,243 is known to be found in most
      patients with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and
      stroke-like episodes). We report a 30 year-old female patient of MELAS, diagnosed
      5 years ago, who presented herself to our ENT outpatient department because of
      her bilateral tinnitus and progressive hearing impairment since 4 years ago. Two
      sequential pure tone audiograms showed bilateral symmetrical progressive
      sensorineural hearing loss, especially in the high frequency area in 1993 and
      1996. The pure tone average was R-45 dB, L-47 dB in 1993 and R-62 dB, L-67 dB in
      1996. Hearing loss is an important feature in MELAS syndrome and reported to be
      seen in about 30% of patients. It is often the first clinical symptom, too. In
      any case, mitochondrial cytopathies need to be considered by the otologist in
      forming a diagnosis of sensorineural hearing loss (SNHL), particularly in cases,
      which present adult-onset progressive hearing loss and neurologic symptoms before
      50 years of age.

PMID- 9780604
TI  - Pancreatic pseudocyst involving the spleen.
AB  - The pseudocyst of the pancreas is a frequent complication of acute pancreatitis.
      The splenic involvement from the pancreatic pseudocyst is an uncommon entity. A
      40-year-old man, who had a five-year history of alcohol consumption, was referred
      to our hospital for treatment of throbbing pain over left upper quadrant (LUQ) of
      the abdomen. Except for LUQ tenderness, physical examination was essentially
      normal. MRI showed two cystic lesions in splenic hilum and pancreatic tail, and
      prominent vessels in left infrasplenic area and gastrosplenic ligament.
      Angiography revealed splenic vein thrombosis. Because of persistent LUQ pain, he
      underwent laparotomy. During the operation, we found the cysts in pancreatic tail
      and splenic hilum. The cystic content was aspirated to check amylase, which
      showed the level of amylase being as high as 20,000 IU/L. The diagnosis of a
      pancreatic pseudocyst involving the spleen was established. Splenectomy and
      distal pancreatectomy were performed to remove both cysts. The pathologic
      examination of the resected spleen showed splenic infarction with cyst formation
      and pancreatic pseudocyst. The patient recovered uneventfully after operation.

PMID- 9780605
TI  - [Effects of half-sized secretory leukocyte protease inhibitor and Chinese
      traditional medicines, yokuinin and mao-bushi-saishin-to, on therapeutic
      efficacies of benzoxazinorifamycin KRM-1648 against Mycobacterium avium complex
      infection induced in mice].
AB  - We examined the effects of such drugs having anti-inflammatory activity as half
      sized secretory leukocyte protease inhibitor (1/2 SLPI) and Chinese traditional
      medicines, Yokuinin (YOK) and Mao-Bushi-Saishin-To (MBST), on therapeutic
      efficacies of benzoxazinorifamycin KRM-1648 against Mycobacterium avium complex
      (MAC) infection induced in mice, since it is possible that these agents inhibit
      the increase in tissue levels of immunosuppressive cytokines due to MAC
      infection. First, Zymosan A-induced murine peritoneal macrophages treated with
      either 1/2 SLPI, YOK or MBST at 37 degrees C for 2 days were infected with M.
      avium N-444 and further cultivated in the medium with or without addition of 1/2
      SLPI, YOK or MBST at 37 degrees C for up to 7 days. Treatment of macrophages with
      these drugs caused some decrease in the intracellular growth of the organisms.
      Secondly, we evaluated effects of 1/2 SLPI, YOK and MBST on the therapeutic
      efficacy of benzoxazinorifamycin KRM-1648 against M. avium infection induced in
      mice. When MAC-infected mice were given KRM-1648 (20 mg/kg) alone, or in
      combination with 1/2 SLPI (100 mg/kg), YOK (50 mg/kg), or MBST (50 mg/kg), by
      gavage, except for 1/2 SLPI which was given via i.p. route, once a week, from day
      1 for up to 8 weeks after infection, these drugs did not affect the expression of
      therapeutic activity of KRM-1648. When MAC-infected mice were given KRM-1648
      alone (once a week), or in combination with YOK (five times per week) or MBST
      (five times per week), MBST increased the expression of therapeutic activity of
      KRM-1648. These findings indicate that suppression of inflammatory reactions
      using MBST is capable to improve the therapeutic efficacy of KRM-1648 in MAC
      infection. Moreover, these results also mean that combined use of these drugs in
      MAC patients receiving KRM-1648 therapy may not cause any disadvantages to the
      therapeutic efficacy of KRM-1648.

PMID- 9780606
TI  - [Clinical evaluation on causes of death in patients with pulmonary tuberculosis
      during the past 3 years (1994 to 1996)].
AB  - We evaluated the cause of death in patients with pulmonary tuberculosis during
      the past 3 years (1994 to 1996). Of 502 tuberculous patients, 58 (11.6%) patients
      died. Most of them were aged or under poor nutritional conditions. Of 378 active
      tuberculous patients, 39 (10.3%) patients died (group A). Of 124 old tuberculous
      patients or cases with extensive sequelae of tuberculosis, 19 (23.4%) patients
      died (group B). In the group A, 15 patients died in spite of improvements in
      tuberculosis lesions. All the intubated patients with active tuberculosis died.
      In the group B, most of patients died of respiratory failure or pneumonia.

PMID- 9780607
TI  - [Tuberculosis of the central nervous system experienced at the International
      Medical Center of Japan].
AB  - In spite of recent advances in diagnosis and chemotherapy of tuberculosis,
      prognosis of tuberculosis of the central nervous system (CNS) is still poor. We
      evaluated clinical characteristics of 14 patients with the CNS tuberculosis (10
      male and 4 female, 21 to 71 years of age) who were hospitalized at IMCJ from 1988
      to 1997. Twelve patients had tuberculous meningitis (2 of them had also
      intracranial tuberculoma), 1 had intracranial tuberculoma and 1 had spinal cord
      tuberculosis. For the acid-fast bacilli, the smears of cerebrospinal fluids (CSF)
      were all negative but the cultures for M. tuberculosis were positive in 5. Using
      PCR method, M. tuberculosis was identified from CSF specimens in 2 out of 9
      culture negative patients, thus suggesting the usefulness of the PCR for the
      rapid diagnosis of CNS tuberculosis. The adenosine deaminase (ADA) levels in CSF
      may provide another diagnostic clue because they were elevated in 8 out of 10
      cases. It is to be noted that there were three patients who developed clinical
      manifestations of CNS tuberculosis after the initiation of chemotherapy for
      pulmonary tuberculosis. In the last five cases, four-drug regimen which included
      PZA, was used with a good result. The success could be related to the addition of
      PZA which penetrates blood-brain barrier just as good as INH. Two patients died
      and one remains unconscious with severe neurological sequelae. The present study
      indicates that positive CSF culture, hydrocephalus and consciousness disturbance
      are important factors in determining poor prognosis of the CNS tuberculosis.

PMID- 9780608
TI  - [A case of miliary tuberculosis with multiple cerebral tuberculoma and spinal
      tuberculosis owing to total delay].
AB  - We reported a case of miliary tuberculosis with multiple cerebral tuberculoma and
      spinal tuberculosis. The case was a 37 year old man. In the last sixteen months
      to the first visit to a hospital, he has been suffering from low grade fever,
      cough, and back pain, but he bared his symptoms without any therapy. At a
      hospital he first visited, he was told that he might have a malignant disease,
      which prevented him to visit the hospital because of a fear for his disease. Six
      months later, he was admitted to other hospital because of severe back pain. At
      last, he was diagnosed as tuberculosis and referred to our hospital. By the
      examinations on admission he was diagnosed as multiple cerebral tuberculoma and
      spinal tuberculosis, and anti-tuberculous therapy was started. It is thought that
      his severe disease status on admission is caused by the total delay, namely the
      delay in visiting a doctor and the doctor's delay in making diagnosis.

PMID- 9780609
TI  - [The coexistence of pulmonary tuberculosis and thymoma a case report].
AB  - A 33-year-old male was admitted with complaints of cough, dysphagia, and swelling
      of face and upper extremities. Chest X-ray and CT scan revealed a large
      mediastinal mass and infiltrates in the right upper lobe. Percutaneous biopsy
      proved the mediastinal tumor as thymoma with cellular atypia. After irradiation,
      the tumor was surgically removed. Caseous epitheloid granulomas were found in the
      dissected mediastinal lymph nodes. AFB (Acid fast bacillus) stain of the
      patient's gastric fluid was positive for Mycobacterium. The coexistence of these
      two diseases was incidental, however, this case suggested that clinicians should
      perform careful evaluation of lung parenchyma as well as mediastinum on chest X
      ray to identify occult diseases including pulmonary tuberculosis in patients with
      mediastinal mass lesion.

PMID- 9780610
TI  - Delay equation analysis of human respiratory stability.
AB  - A mathematical analysis of the stability in human respiration, based on the tau
      decomposition method, is conducted on a simple, but realistic CO2 model of the
      respiratory system. This model incorporates a two-compartment representation
      (lungs and tissues) for the plant and a very general class of controller. By
      deriving an explicit stability criterion, the stability domain of the respiratory
      system can be characterized. We quantify the influence of four major parameters
      of respiratory instability, i.e. transport delay, lung volume, and equilibrium
      values of lung CO2 partial pressure and controller gain. We demonstrate the
      existence of a bifurcation point and periodic solutions, giving some
      characteristics of solutions near the bifurcation point.

PMID- 9780611
TI  - Optimal control of the cell dynamics in the granulosa of ovulatory follicles.
AB  - The aim of this paper is to seek for the optimal cellular changes in the
      granulosa of ovarian follicles, leading to ovulation in minimal time. The
      granulosa cell population consists of proliferating, differentiated and apoptotic
      cells. Cell numbers are ruled by a system of differential equations, in which the
      control variables are the cell cycle exit and apoptosis rates. The conditions for
      ovulation are represented by three different constraints on the granulosa final
      state. We prove that the optimal strategy consists in applying permanently the
      minimal apoptosis rate and in switching the cell cycle exit rate from its minimal
      bound to its maximal one. We finally apply the optimal strategy on data providing
      the changes in the total cell number of ewe follicles during their terminal
      development.

PMID- 9780612
TI  - Influence of delayed viral production on viral dynamics in HIV-1 infected
      patients.
AB  - We present and analyze a model for the interaction of human immunodeficiency
      virus type 1 (HIV-1) with target cells that includes a time delay between initial
      infection and the formation of productively infected cells. Assuming that the
      variation among cells with respect to this 'intracellular' delay can be
      approximated by a gamma distribution, a high flexible distribution that can mimic
      a variety of biologically plausible delays, we provide analytical solutions for
      the expected decline in plasma virus concentration after the initiation of
      antiretroviral therapy with one or more protease inhibitors. We then use the
      model to investigate whether the parameters that characterize viral dynamics can
      be identified from biological data. Using non-linear least-squares regression to
      fit the model to simulated data in which the delays conform to a gamma
      distribution, we show that good estimates for free viral clearance rates,
      infected cell death rates, and parameters characterizing the gamma distribution
      can be obtained. For simulated data sets in which the delays were generated using
      other biologically plausible distributions, reasonably good estimates for viral
      clearance rates, infected cell death rates, and mean delay times can be obtained
      using the gamma-delay model. For simulated data sets that include added simulated
      noise, viral clearance rate estimates are not as reliable. If the mean
      intracellular delay is known, however, we show that reasonable estimates for the
      viral clearance rate can be obtained by taking the harmonic mean of viral
      clearance rate estimates from a group of patients. These results demonstrate that
      it is possible to incorporate distributed intracellular delays into existing
      models for HIV dynamics and to use these refined models to estimate the half-life
      of free virus from data on the decline in HIV-1 RNA following treatment.

PMID- 9780613
TI  - Optimal harvesting policy for single population with periodic coefficients.
AB  - In this paper, we examine the exploitation of single population modeled by time
      dependent Logistic equation with periodic coefficients. First, it is shown that
      the time-dependent periodic Logistic equation has a unique positive periodic
      solution, which is globally asymptotically stable for positive solutions, and we
      obtain its explicit representation. Further, we choose the maximum annual
      sustainable yield as the management objective, and investigate the optimal
      harvesting policies for constant harvest and periodic harvest. The optimal
      harvest effort that maximizes the annual-sustainable yield, the corresponding
      optimal population level, the corresponding harvesting time-spectrum, and the
      maximum annual-sustainable yield are determined, and their explicit expressions
      are obtained in terms of the intrinsic growth rate and the carrying capacity of
      the considered population. Our interesting and brief results generalize the
      classical results of Clark for a population described by the autonomous logistic
      equation in renewable resources management.

PMID- 9780614
TI  - Modeling carcinogenesis under a time-changing exposure.
AB  - A model of carcinogenesis for fractionated and continuous exposure is developed.
      The model is discussed from two points of view. First a "surface" statistical
      model is introduced by making assumptions about the hazard function for the time
      of tumor latency. Later it is shown that the model can be interpreted in a
      mechanistic sense as a discrete and a mixed discrete/continuous counterpart of a
      model of carcinogenesis recently proposed by Yakovlev and Polig [A. Yakovlev, E.
      Polig, Math. Biosci. 132 (1996) 1]. Two counteracting effects are combined: a
      protective multiplicative effect of the exposure on the hazard function along
      with an additive effect of cancer induction responsible for an additional hazard.
      The model is used to revisit the analysis by Yakovlev et al. [A. Yakovlev, W.
      Muller. L. Pavlova, E. Polig, Math. Biosci. 142 (1997) 107] of lymphoma-free
      survival in irradiated mice under acute and fractionated exposure.

PMID- 9780615
TI  - [Dolichoarteriopathy (kinking, coiling,tortuosity) of the carotid arteries and
      cardiovascular risk factors].
AB  - BACKGROUND AND AIMS: The clinical significance of dolichoarteriopathies (kinking,
      coiling, tortuosity) and their prognosis have not yet been clearly defined. A
      study was performed in outpatients in order to evaluate the cardiovascular risk
      factors of dolichoarteriopathies. METHODS: A total of 1220 subjects (620 males
      and 600 females, aged between 25 and 89 years old) were examined using color
      Doppler ultrasonography of the extracranial carotid arteries with an Acuson 128
      XP-5 scan and 7 MHz linear probe. The reason for the test was the presence of
      clinical symptoms or cardiovascular risk factors. The risk factors studied
      included: arterial hypertension [systolic (> 140 mmHg) and/or diastolic arterial
      pressure (> 90 mmHg)], hypercholesterolemia (total cholesterol > 200 mg/dl),
      diabetes mellitus, cigarette smoking. Patients were divided as follows: patients
      with arterial hypertension alone, patients with arterial hypertension associated
      with other cardiovascular risk factors (hypercholesterolemia, diabetes mellitus,
      smoking), patients with other cardiovascular risk factors (hypercholesterolemia,
      diabetes mellitus, smoking), patients without risk factors. RESULTS: In 316
      (25.9%) patients with dolichoarteriopathies, arterial hypertension alone was
      present in 98 (31%), arterial hypertension associated with other cardiovascular
      risk factors in 85 (26.3%) and other cardiovascular risk factors in 54 (17%),
      whereas 75 (25%) did not present cardiovascular risk factors. In the 904 subjects
      without dolichoarteriopathies, arterial hypertension alone was present in 254
      (28%), arterial hypertension associated with other cardiovascular risk factors in
      213 (23.6%) and other cardiovascular risk factors in 191 (21.1%), whereas 241
      (27.2%) did not present cardiovascular risk factors. In 316 subjects with
      dolichoarteriopathies, cardiovascular risk factors were equally present in the
      two sexes without statistically significant differences. In cases with kinking
      and tortuosity, cardiovascular risk factors were equally present in the two
      sexes, whereas colling was more frequently associated with arterial hypertension
      alone in males and with arterial hypertension associated with other risk factors
      in females, showing a statistically significant difference. CONCLUSIONS: The
      findings of this study reveal that the presence of risk factors in patients with
      dolichoarteriopathies is comparable to that in subjects without
      dolichoarteriopathies. Also in the three types of dolichoarteriopathies (kinking,
      coiling and tortuosity), cardiovascular risk factors were equally present.
      Therefore, these results appear to lay the role of arterial hypertension or other
      cardiovascular risk factors in the genesis of diolichoarteriopathies open to
      question.

PMID- 9780616
TI  - [Calcium antagonist vs diuretics. Doppler velocimetric monitoring of the carotid
      flow in patients with essential hypertension].
AB  - BACKGROUND: In the period from 1995 to 1996, 19 patients with a range of 180-200
      mmHg and 95-110 mmHg respectively for systolic and diastolic pressure, have been
      examined by Doppler monitoring. METHODS: Nine patients were treated with
      lacidipine (4 mg/die) and 10 were treated with idroclorotiazide + amiloride (50
      mg every other day). The IPP and the IDC were end points to value the arterial
      compliance and the remodynamic flow in common carotid. RESULTS: The humeral blood
      pressure was valued every morning and Doppler monitoring of common carotid 30 and
      60 day after treatment. The carotid blood flow and cerebral perfusion had a
      significant amelioration with calcium antagonists and an increase of IDC with a
      decrease of IPP were found. CONCLUSIONS: This study demonstrates the role of
      calcium antagonists not only as antihypertensive drug, but also to prevent, to
      check and to improve progression of ateromatic injury. The conclusions is drawn
      that Doppler monitoring is a satisfactory scientific method to obtain information
      on features of arterial wall without excessive cost.

PMID- 9780617
TI  - Femoro-femoral graft after unilateral obstruction of aorto-bifemoral bypass.
AB  - BACKGROUND: Thrombosis is the most frequent late complication of surgical
      procedures in the aortofemoral area. In the presence of aortobifemoral bypass,
      graft limb occlusion generally occurs within the first two years. Various
      techniques have been proposed to revascularize the ischemic limb. Personal
      experience in the treatment of occlusions of aorto-femoral bypasses branch by
      femoro-femoral bypasses is reported and the immediate and long-term results are
      analyzed. METHODS: The study was retrospective and the medium follow-up was 51
      months (1-14 years). The patients were all operated from 1976 to 1995 in the
      Division of Vascular Surgery of the University of Bari. The group consisted of 40
      patients affected by unilateral occlusion that occurred after aorto-femoral
      bypass. The femoro-femoral bypass was performed using non-ringed 6 or 8 mm Dacron
      prostheses; the proximal anastomosis was made a few cm above the femoral
      anastomosis of the permeable branch of the existing aorto-bifemoral bypass and
      the distal anastomosis on the cross-leg profunda femoris. Postoperative follow-up
      consisted of clinical examination, continuous wave Doppler examination or US
      color-Doppler scan in order to assess the permeability of the graft. RESULTS: The
      immediate results showed 2 and long-term results 9 occlusions of the bypass. No
      perioperative mortality was observed. CONCLUSIONS: In conclusion the authors
      consider the use of femoro-femoral bypass indicated in a high number of patients
      affected by unilateral occlusion of the aorto-bifemoral bypass.

PMID- 9780618
TI  - Nitrate tolerance in patients with effort angina.
AB  - BACKGROUND: In some patients with chronic stable angina the beneficial effects of
      nitrates may result not only from a reduction in venous return, but also from
      their action on coronary circulation. In these patients, rate-pressure product at
      ischemia (RPPI) increases to > 2500 bpm x mmHg after sublingual nitrates (SLN).
      The relative susceptibility of the venous system and the coronary circulation to
      the development of nitrate tolerance and the effects of two different drug
      schedules on the development of tolerance were investigated in patients with
      these characteristics. METHODS: Five patients were treated with isosorbide-5
      mononitrate (IS5MN) 20 bid (8.00 am and 3.00 pm) for 1 week (Group 1) and 5
      patients with IS5MN 40 bid (8.00 am and 8.00 pm) for 1 week (Group 2). Tolerance
      was identified as the decreased effect of SLN; the effects of nitrates were
      evaluated in relation to: reduction in left ventricle area (delta LVA), which had
      been measured using equilibrium radionuclide ventriculograms in LAO 45 degrees;
      this area was considered as an index of the venous return effects; increase in
      RPPI (delta RPPI), which had been assessed by ergometric test; RPPI was
      considered an index of coronary flow reserve. Measurements of LVA and RPPI were
      made in wash-out at the start of the study (delta LVA 1 and delta RPPI 1) and
      after 1 week of treatment (delta LVA 2 and delta RPPI 2). The mean values of the
      differences were then evaluated and compared using Student's "t" test. RESULTS
      AND CONCLUSIONS: In Group 1 patients delta LVA 2 and delta RPPI 2 showed values
      which were similar to delta LVA 1 and delta RPPI 1 (mean value delta LVA 2 47 vs
      mean delta LVA 1 48.2 pixels, p = ns; mean value delta RPPI 2 5264 vs mean delta
      RPPI 1 5536 bpm x mmHg, p = ns). These results suggest that Group 1 patients did
      not develop tolerance either at the coronary or at the venous level. In Group 2
      patients, delta LVA 2 was significantly lower than delta LVA 1 (mean delta LVA 2
      18.4 vs mean delta LVA 1 54 pixels, p < 0.01). This finding indicated tolerance
      to nitrates at the venous level. On the other hand, in all Group 2 patients,
      values of delta RPPI 2, though lower than delta RPPI 1 (mean delta RPPI 2 3095 vs
      mean delta RPPI 1 6083 bpm x mmHg, p < 0.01) were still higher than 2500 bpm x
      mmHg, indicating that the effect of nitrates at the coronary level was preserved.
      These data suggest that in patients treated with high doses of nitrates, the
      effect of these drugs at the coronary level is still present when tolerance has
      already developed at the venous level.

PMID- 9780619
TI  - [Secondary aorto-enteric fistula].
AB  - Aortic graft fistula is a rare and life-threatening complication after aortic
      reconstruction. The incidence ranges from 0.5 to 4%, and even if the diagnosis
      and treatment is appropriate, the results of surgery are poor: mortality rate
      ranges from 14 to 70%. The optimal method of treatment is still controversial;
      prosthetic removal and extra-anatomic bypass has been advocated as the standard
      method, but more recently, because the high mortality rate associated with this
      procedure, some have prompted to recommend in situ aortic graft replacement as a
      more successful treatment. Personal experience with incidence (0.7%) outcome and
      mortality (57%) in 7 patients treated over a period of 6 years (1990-1996) is
      reported. Results from this group are compared with another group (6 patients)
      previously treated (1975-1982) for the same pathology. Our results after 10
      years, show the same incidence (0.7 vs 0.6%) and an elevated and unchanged
      mortality (57 vs 66%). Better results in the management of aorto-enteric fistulas
      could be achieved with the removal of infected infrarenal aortic prosthetic
      grafts and in situ homografts replacement.

PMID- 9780621
TI  - [Laparoscopic approach to appendiceal emergencies. Our experience. Preliminary
      results].
AB  - Laparoscopic surgery in acute appendectomy is a very much debated subject also
      for skilled teams of mini-invasive surgery. The authors review 25 urgent
      laparoscopic interventions for acute appendicitis, treating some technical
      aspects of trocar introduction and Endoloops and EndoGia employment in this
      field. They conclude by emphasizing that the laparoscopic approach for acute
      appendicitis is the treatment of choice, considering the good results and the
      future prospects of laparoscopic versus open surgery.

PMID- 9780620
TI  - [Cardiac echinococcosis. Report of a case].
AB  - Cardiac hydatid disease represents 0.02-2% of the possible locations of the
      parasite. The case of an asymptomatic 60-year-old male patient, hospitalised for
      mnesic and cognitive disease, and with history of hepatic and pulmonary
      echinococcosis is reported. The patient showed a cardiac cyst localised in the
      mediobasal portion of the ventricular septum, with partial obstruction of the
      left ventricular outflow tract and with alteration of the left ventricular
      compliance. This case is of particular interest either for the rarity of cardiac
      localization or disagreement between the severity of anatomic involvement and
      absence of correlated symptoms. Therefore all patients affected by hydatid
      disease could be routinely investigated by 2D echo because this imaging technique
      is non invasive, feasible and has a high sensitivity for detecting intracardiac
      echinococcal cysts.

PMID- 9780622
TI  - [Laparoscopic and thoracoscopic reintervention after mini-invasive surgery in
      emergencies].
AB  - One-hundred-eighty patients underwent emergency minimally invasive procedures
      (laparo and thoracoscopy) in the last two years. In twelve postoperative
      drawbacks another surgical procedure was performed. Laparoscopic or thoracoscopic
      exploration was undertaken in 8 cases while open surgery was done in 4.
      Complications and surgical overtiming rate was higher after endoscopic than open
      surgery. This approach allows us to correct very few and selected disease when a
      skilled surgical team is available especially during reoperations.

PMID- 9780623
TI  - [Response of interleukin-6 in patients undergoing a laparoscopic or laparotomic
      cholecystectomy].
AB  - BACKGROUND: It is well known that surgery induces an acute inflammatory response
      associated with significant increase of interleukin-6 (IL-6) and C reactive
      protein (CRP). Laparoscopic cholecystectomy (LC) is a so called "mini-invasive"
      surgical intervention and on the basis of this consideration it has been
      investigated if and how serological markers of inflammation are modified in
      patients after laparoscopic cholecystectomy compared to patients undergoing open
      cholecystectomy. METHODS: The acute phase of inflammation (IL-6, CRP and body
      temperature) was evaluated in 53 patients one day before surgery and p.o. after
      1, 3 and 6 days; 26 patients underwent "open" cholecystectomy and 27 LC. RESULTS:
      One day after surgery patients with open cholecystectomy showed significant
      increase (p < 0.05) of IL-6, CRP and body temperature, while these parameters
      were almost unchanged in patients with LC. In patients with "open"
      cholecystectomy, 2 p.o. complications (pneumonia) were observed. CONCLUSIONS: In
      conclusion, LC, although it requires longer operative time, strongly reduces p.o.
      pain, hospitalization, promotes earlier recovery and return to normal activity,
      avoiding the acute phase of p.o. inflammation with better p.o. morbidity compared
      to open surgery.

PMID- 9780624
TI  - [Percutaneous transcatheter therapy of visceral pseudoaneurysms].
AB  - BACKGROUND: The purpose of this work is to show the effectiveness of percutaneous
      embolization therapy in the treatment of visceral arterial pseudoaneurysms and to
      propose the method as a valid alternative to surgery. METHODS: Twenty-eight
      patients with visceral artery pseudoaneurysms were treated: 10 of them were
      hepatic; 9 renal; 7 duodenal-pancreatic; 1 splenic and 1 of the celiac trunk.
      Materials employed were: Gianturco metallic coils, Spongostan and Poli-Vinyl
      Alcohol. RESULTS: Immediate success was obtained in all cases; recurrences
      occurred in 5 patients (18%) and they have all been successfully retreated with
      percutaneous method; complications occurred in 3 patients (10%) and they were all
      directly related to the pre-existing pathology and not to the percutaneous
      treatment. CONCLUSIONS: To obtain the best results from embolization, it is
      necessary to respect some conditions regarding the correct choice of embolic
      materials, the superselective catheterization of the injured artery and the low
      injection pressure of the contrast medium in order to avoid rupturing the thin
      pseudoaneurysmatic wall. The advantages of the percutaneous treatment are: less
      trauma, local anesthesia, reduction of the time between diagnosis and therapy,
      reduction of hospitalization stay and limitation of parenchymal destruction,
      Complications are relatively not frequent and in no cases the percutaneous
      therapy compromised the surgical intervention when it became necessary.

PMID- 9780625
TI  - [Preliminary experience with radioimmuno-guided surgery of primary neoplasms of
      the lung].
AB  - BACKGROUND: Radioimmunoguided surgery (RIGS) can be a valid option in the
      management of lung cancer as well as neoplasms in other anatomic sites. METHODS:
      We evaluated the usefulness of radioimmunoguided surgery (RIGS) in the staging of
      primitive non small cell lung cancer. Intraoperatively, this technique can define
      the lymph nodes involvement and thus, the radicality of the resection. In the
      first stage of our study, we looked for the epitope TAG 72 in 45 patients with
      primary non small cell lung cancer. The epitope was found by immunochemistry in
      only 6 cases. The only one operable patient was injected with monoclonal antibody
      B 72.3, that was 125I-labelled. RESULTS: At the operation, the monoclonal
      antibody showed no selectivity for neoplastic cells. Neoplastic tissue and
      healthy tissue showed a similar detection of the monoclonal antibody both
      intraoperatively and at the histochemical study. Because of the problems related
      with this method--e.g. technical difficulties, excessive wasting of time and lack
      of imaging--we modified our strategy. In this second stage of our study we used
      fragments of murine anti-CEA monoclonal antibody F023C5. The protocol was
      performed in 11 patients with squamous cell lung cancer. In one patient operated
      on for an excavated cancer(not well-defined at the immunoscintigraphy)
      intraoperative detection was negative while the ex vivo counts were significant:
      the neoplastic tissue showed a radioactivity twice higher than healthy tissue.
      Furthermore, the RIGS found a small intraparenchimal lymph node that was seen
      neither by CT nor by immunoscintigraphy. CONCLUSIONS: Our data are still
      preliminary, but with improvement of the technique and the use of more specific
      monoclonal antibodies the RIGS could become a helpful method, able to improve the
      radicality of surgery for lung cancer.

PMID- 9780626
TI  - Palliation of tracheobronchial malignant obstruction with metal stents in
      emergency conditions.
AB  - BACKGROUND: Endoluminal obstruction, caused by tracheobronchial malignancies, can
      require urgent treatment in case of severe respiratory distress. In emergencies,
      self-expanding metal stents can be endoscopically employed to solve acute
      symptoms. METHODS: Between April 1992 and August 1996, 7 patients were treated by
      positioning of metal stents in emergency conditions and observed to verify the
      immediate efficacy of endoscopic therapy. Tracheal stenosis, stenosis of trachea
      and right main bronchus and obstruction of trachea and left main bronchus were
      present in 5, 1 and 1 patient, respectively. Metal stents for intravascular use
      (Wallstent, Schneider, Zurich, Switzerland) were positioned on a guide wire by
      fiber- or video-bronchoscope, after local anaesthesia, monitoring the arterial
      oxygen saturation of every patient. RESULTS: In six patients breathlessness was
      resolved immediately. The last patient, suffering from severe mediastinal
      involvement, died from cardiac failure. No complication occurred. Mean survival
      was 40 days. CONCLUSIONS: Self-expanding metal stent placement is an easy and
      safe method, does not require general anaesthesia, is less traumatic and well
      tolerated, is quick to be performed and then can be used in emergencies.
      Nevertheless, it is impossible to remove the stent in case of malpositioning.
      Although this group is small, endobronchial stenting using metallic prostheses
      permits immediate ventilation and palliation of large airway obstruction.

PMID- 9780627
TI  - [Uninodular bronchioalveolar carcinoma. Apropos of 10 operated cases].
AB  - BACKGROUND: This study reports 10 cases of uninodular bronchiolo-alveolar
      carcinoma (BAC) operated on in the General Surgery and Organ Transplantation
      Institute of the University of Parma between January 1st 1981 and December 31st
      1995. METHODS: Seven patients were males and three females, mean age was 65 (DS
      11, range 37-75) and globally accounted for 6.4% of all surgically treated lung
      malignant tumors. RESULTS: Hospital mortality was null; one patient was treated
      with assisted ventilation four days after surgery for respiratory insufficiency.
      Actuarial survival at 36 and 60 months was 48% and 36% respectively; survival
      rates were not significantly different at log-rank test from squamous carcinoma
      (46.2% at 36 months, 35% at 60 months) and adenocarcinoma (50.5% at 36 months,
      34.3% at 60 months). The analysis of other series of literature shows
      significantly higher survival rates at 5 years for BAC than for adenocarcinoma
      (55.6% vs 40%). CONCLUSIONS: Broader series are needed for statistical
      confrontation with other histological types by stage and grade. There is no
      evidence of peculiar prognostic or clinical features in this histological type of
      pulmonary malignancy, prognosis so far is in fact conditioned by the same factors
      of other non small cell lung carcinomas.

PMID- 9780628
TI  - [Bilateral inguinal hernia. Which treatment?].
AB  - The authors present a series of 70 bilateral inguinal hernias selected from a
      total of 641 inguinal hernias operated from May 1994 to November 1996 using
      alloplastic surgery. They discuss the most appropriate methods of access for
      treating this pathology in a single operation, and propose inguinal access as the
      most preferable method owing to its easy execution and apparently greater safety.
      Laparoscopic techniques should be reserved for special cases such as pluri
      recidivating hernias.

PMID- 9780629
TI  - [Mannhein index in the prognosis and treatment of acute peritonitis].
AB  - BACKGROUND: Early prognostic evaluation of patients affected by acute peritonitis
      is really desirable to program a correct therapeutic plan, selecting high-risk
      patients for more aggressive therapeutic procedures. The Mannheim peritonitis
      index is reliable and easy to apply, so its use is possible without the need of
      intensive care units. METHODS: Between 1991 and 1995 a total of 235 patients were
      operated on for acute peritonitis. A retrospective study on this group of
      patients was performed in order to estimate prognostic reliability of Mannheim
      peritonitis index. RESULTS: The overall mortality was 8.1%; for patients with a
      score less than 26 the mean mortality rate was 2% and for score greater than 26,
      40.5%. This score is the threshold over which the therapeutic approach have to be
      more aggressive; planned multiple laparotomies or the open abdomen technique
      could be the best options to explore and clean up the peritoneal cavity from
      septic debris. In personal experience, all patients who died had residual sepsis
      in peritoneal cavity.

PMID- 9780632
TI  - [Gastric polypoid angioma: a rare cause of bleeding in the elderly. Report of a
      case and review of the literature].
AB  - In 10,700 upper gastrointestinal endoscopies performed between 1990 and 1995; one
      case of gastric haemangioma was observed. The rarity of this tumour, which
      represents 0.05% of all the digestive neoplasms is underlined and its features
      and clinical history are reported. This case and the other four reported in Italy
      during the last fifteen years are critically reviewed. The various diagnostic
      therapeutic pictures emerging from literature are examined.

PMID- 9780631
TI  - [Infection prophylaxis in cardiovascular surgery].
AB  - MATERIALS AND METHODS: In the period 1986-1994, 2950 patients with cardiovascular
      diseases were surgically treated. In 2104 cases we placed biological or synthetic
      grafts to maintain vascular continuity. The most common has turned out to be
      abdominal aortic aneurysm. We treated 783 cases in emergency conditions. Staging
      and localization of infection has been the first aim in patients with synthetic
      vascular grafts. We studied signs and symptoms related to infections. In all
      cases we discovered the microorganism responsible of infection we started
      antibiotic therapy. RESULTS: Surgical infection incidence is 4.9% (154 cases).
      Series analysis has evidenced a decrease in infection incidence in the period
      1986-1994. The most frequent infections are: the urinary tract infection (59
      cases, 38.5%) followed by surgical wound infection (37 cases, 24.1%), respiratory
      tract infection (27 cases, 17.5%), vascular graft infection (23 cases, 14.4%).
      All patients underwent a preoperative antibiotic prophylaxis with 2 degrees-3
      degrees generation cephalosporines. We noted a higher graft infection incidence
      in patients treated with aortobifemoral reconstruction. We handled surgical
      infection following two main directions: 1-antibiotic therapy, 2-surgical
      treatment and antibiotic therapy. CONCLUSIONS: We noted surgical technique
      improvement and correct application of an antibiotic prophylaxis form has turned
      out to be the "gold standard" in order to reduce cardiovascular surgical
      infections. To reduce sepsis or graft infection we can work on either of the
      following: 1) antibiotic therapy; 2) operative time reduction; 3) try to limit
      vascular surgery in case of concomitant gastrointestinal surgical disease; 4)
      using alloplastic vascular grafts with high biological compliance; 5) patency
      time reduction of invasive diagnostic technique.

PMID- 9780630
TI  - [Treatment of the nephrotoxicity of immunosuppressive drugs with insulin-like
      growth factor-I].
AB  - BACKGROUND: Delayed graft function is a common and severe complication after
      cadaveric kidney transplantation. Besides a more complicated postoperative
      course, DGF can worsen the overall graft survival. In particular, DGF enhances
      the nephrotoxicity of mainstream immunosuppressants cyclosporine and FK506. This
      study evaluates a new therapeutical approach to the treatment of DGF related
      nephrotoxicity, based on the administration of IGF-I. METHODS: Sixty inbred Lewis
      rats underwent a bilateral clamping of the renal pedicles (20') as standard
      damage. The animals were stratified in six groups, according to the postoperative
      treatment. Group 1 served as control and received only the standard ischemic
      injury. Cyclosporine and FK506 were added in groups 3 and 5. Groups 2, 4 and 6
      had the same treatment of groups 1, 3, 5 respectively, plus the administration of
      IGF-I. Blood samples were drawn daily to evaluate creatinine and BUN for 7 days.
      RESULTS: The rats treated with IGF-I had significantly better values compared to
      the respective controls (2-way ANOVA, p < 0.05). CONCLUSIONS: In conclusion, IGF
      I improves the nephrotoxicity of mainstream immunosuppressants in this model. Its
      use is potentially beneficial for transplantation.

PMID- 9780633
TI  - [Paraesophageal hiatal hernia].
AB  - Paraesophageal hiatal hernia is an uncommon disease but it frequently presents in
      aged people, causing chronic vague abdominal symptoms up to surgical emergencies
      from incarceration, strangulation or obstruction. The authors describe the
      physiopathology and clinical anatomical features of paraesophageal hiatal hernia.
      Important diagnostic radiological and instrumental aspects are then illustrated,
      versus sliding esophageal hiatal hernia. There are followed by a description of
      possible complications of this lesion and therapeutic implications.

PMID- 9780634
TI  - [Duodenal schwannoma. Clinical considerations].
AB  - The recent observation of a case of schwannoma in the second part of the duodenum
      lead the authors to a literature survey in order to state the present knowledge
      of this subject. Schwannoma is an ectodermal neoplasm arising from the nerve
      sheath that envelop axons. In the gastrointestinal tract these tumours can
      concern cells of the myentericus and submucosus plexus of the intestinal wall. A
      duodenal location is extremely rare. Gastroduodenal endoscopy, abdominal
      ultrasonography and CT scan were found as important investigatory tools, but only
      histological examination of the excised tissue suggests the definitive diagnosis.
      Therapy consists in the radical excision of the tumour; this is rarely obtained
      by endoscopic way because of the submucosal neoplastic growth. Then a surgical
      laparotomic approach is more often required and it allows to perform local
      excisions through a duodenotomy, partial duodenectomy or ampullectomy and more
      complex operations, like a cephalic duodenopancreatectomy, in front of extended
      papillar involvement. The latter was the suitable treatment for radical removing
      of the juxtapapillar schwannoma reported by the authors; the uneventful
      postoperative course, the patient's excellent general conditions and nutriture at
      12 months confirm the validity of the therapeutic policy.

PMID- 9780635
TI  - [Jejunal diverticulosis. Presentation of a clinical case].
AB  - Jejunal diverticulosis is a rare and often asymptomatic disease, generally
      presenting as an occasional finding during laparotomy for other diseases. There
      are no established criteria for the treatment of such diverticula. Due to the
      possible onset of acute complications, surgical management must be considered.
      Personal experience on a case of jejunal diverticulosis in a woman who presented
      with acute complications of surgical peritoneal adhesions is described. Through
      examinations of small intestine discovered many diverticula, mainly in the
      mesenteric side; two diverticula were particularly large. Even though there
      appeared to be no symptoms due to the diverticula, major diverticula were
      considered at risk for acute complications. Because their reduction was not
      easily achievable, they were resected and enterotomies were stitched.
      Postoperative course was uneventful and after 2 years the patient is alive and
      well. Features of this rare entity are analyzed with regard to data reported in
      the literature, with special reference to some pathogenetic theories.

PMID- 9780636
TI  - [A rare form of intestinal perforation: adenocarcinoma of the ileum. Presentation
      of a clinical case].
AB  - Ileal carcinoma is not frequent and its diagnosis is preoperatively quite
      difficult. The surgical approach often depends more on the on table situation
      than on a precise therapeutic protocol. The histological result is sometimes a
      real negative surprise and the five year survival of patients is similar to those
      operated for colonic carcinoma at the same stage.

PMID- 9780637
TI  - [Carcinoid of the appendix. Observations on 4 cases].
AB  - Four cases of carcinoid tumors of the vermiform appendix are reported. Clinical
      presentation in 3 cases was suggestive of acute appendicitis and they were
      submitted to appendicectomy. The carcinoid tumor was discovered by the
      pathologist on specimen of appendix. The tumors's size, less than 2 cm, the
      absence of serosal involvement and lymphatics invasion suggested that simple
      appendicectomy was a satisfactory treatment for such patients. Occasionally
      clinical presentation of appendiceal carcinoid is characterized by symptoms of
      intestinal obstruction or intussusception, palpable mass, bleeding. In the fourth
      patient, that had symptoms consistent with ileal occlusion, we found at
      laparotomy a bulky tumor of the base of appendix infiltrating and obstructing the
      cecum and right colon, without liver metastases. A right hemicolectomy with end
      to-end anastomosis was performed. Aggressive behaviour of this tumor was also
      revealed by the single pulmonary metastasis, finding very uncommon in carcinoid
      of appendix. This patient died postoperatively, at 25th day, of septic abdominal
      complications, secondary to anastomotic leak. The former patients at clinical and
      radiological (CT scan) follow-up performed at 3, 12, 36 months respectively, are
      still alive and disease free.

PMID- 9780638
TI  - [Pulmonary metastasis from an eccrine carcinoma: thoracic perfusion with the
      aorto-caval stop-flow technique. Description of a clinical case].
AB  - A case of a 64-year-old man with eccrine carcinoma arising from hand skin is
      reported. At the time of diagnosis he showed bilateral pneumonic metastases.
      Although the patient underwent two systemic chemotherapy lines, he showed further
      progressive disease of the lung. For this reason a third chemotherapy line was
      started through thoracic stop-flow infusion. In this way, a five month stable
      disease had been achieved. The patient died 7 months later for progressive
      disease. The rarity of this disease, the uncertain treatment, the feasibility and
      efficacy of thoracic stop-flow infusion are underlined and further studies are
      suggested.

PMID- 9780639
TI  - [Parapharyngeal involvement in neoformation of the deep parotid lobe].
AB  - The parapharyngeal space can be often interested by the extension of neoplasms
      starting at the deep lobe of the parotid gland level. According to many
      international authors, usually benign neoplasm originating at the parotid gland,
      tend to grow in the above mentioned area, while malignant tumors invade more
      easily the infratemporal fossa. Several diagnostic methods and ways of
      approaching the benign tumors of the parapharyngeal space have been proposed over
      the years. Personal experience at the Maxillo-Facial Department of the University
      of Rome "La Sapienza" and a typical clinical case for the diagnostic approach and
      surgical technique used by the authors, is described.

PMID- 9780640
TI  - [Traditional cutaneous suture and synthesis with Fasterzip. Comparative esthetic
      results].
AB  - A group of 20 patients underwent plastic surgery for inguinal hernia. In 10 cases
      the incision was sutured using a traditional technique, whereas in 10 cases the
      wound was joined using Fasterzip. The cosmetic appearance of the wound in the two
      groups was compared at 8, 30, 60 and 90 days after surgery. It was found that the
      use of Fasterzip was significantly better during the initial phase, but as the
      scarring process progressed, the differences became less evident.

PMID- 9780641
TI  - [Sacrococcygeal cyst or "pilonidal sinus"].
AB  - The acquired theory of puncture of hairs on the side of natal cleft is popular.
      There is still controversy on "pilonidal sinus" surgical treatment. A
      modification in the natal cleft cicatrization should be the correct surgical
      therapy. Postoperative treatment as hairs removal, infection control, wound
      healing are mandatory.

PMID- 9780642
TI  - Change in Ca2+ sensitivity of cerebrovascular smooth muscle in experimental
      chronic cerebral vasospasm.
AB  - The mechanism of chronic cerebral vasospasm was investigated by examining the
      relation between cytosolic Ca2+ level ([Ca2+]i) and muscle contraction in
      vascular smooth muscle after experimental vasospasm produced by the two
      hemorrhage method in the canine basilar artery. [Ca2+]i and tension were recorded
      simultaneously with a fluorimeter using the arterial strips with a Ca2+
      indicator, fura-2. High K+ concentration (72.4 mM) and U-46619 (thromboxane A2
      analogue, 10(-8) M) were used as stimulants. The increase in contractile tension
      per [Ca2+]i per unit cross-sectional area was calculated, and compared for the
      vasospasm and the control groups. The increase in [Ca2+]i in the vasospasm group
      was smaller than that in the control group, so the increase in tension per
      [Ca2+]i per unit sectional area was larger in the vasospasm group. This value was
      much larger for the contraction induced by U-46619 than that induced by high K+
      concentration in both groups. These results suggest that there is an increase in
      the basal Ca2+ sensitivity of the contractile elements in vasospastic vessels. In
      addition, the U-46619-induced increase in Ca2+ sensitivity seemed to be augmented
      in the vasospasm group.

PMID- 9780643
TI  - Cerebral revascularization using muscle free flap for ischemic cerebrovascular
      disease in adult patients.
AB  - The efficacy of encephalo-myo-synangiosis (EMS) using muscle free flap was
      evaluated for the treatment of ischemic cerebrovascular disease in adult
      patients. Three patients with adult moyamoya disease and three patients with
      atherosclerotic ischemic cerebrovascular disease were treated. EMS used four
      latissimus dorsi muscles and two serratus anterior muscles. Postoperative
      selective angiography showed collateral circulation from the transferred muscle
      to the brain in four of the six patients. The other two patients showed patent
      nutrient artery of the transferred muscle flap. Cerebral blood flow study
      disclosed postoperative improvement of perfusion reserve capacity in all sides.
      One patient suffered a perioperative stroke by hemoconcentration due to poor
      control of diabetes mellitus. The mean follow-up period was 23 months. EMS using
      muscle free flap is a possible procedure in selected patients with impaired
      cerebral perfusion reserve capacity due to multiple stenosis or occlusion of
      cerebral arteries including moyamoya disease or who required cerebral blood flow
      augmentation in the anterior and/or posterior cerebral artery territories due to
      internal carotid artery occlusion.

PMID- 9780644
TI  - Growth inhibition of experimental glioma by human interferon-beta superinduced by
      cationic liposomes entrapping polyinosilic:polycytidilic acid.
AB  - Intracellular production of human interferon-beta (HuIFN-beta) was enhanced in
      three glioma cell lines (U251-MG, U251-SP, and U251-NN) using modified
      superinduction with cationic liposomes containing polyinosilic:polycytidilic acid
      (polyI:polyC), initially given with cycloheximide, to decrease the toxicity due
      to polyI:polyC. Modified superinduction had a significantly (p < 0.02-0.0001)
      greater inhibitory effect on all three glioma cell lines, and less toxicity than
      superinduction. A pilot trial in experimental gliomas implanted into nude mice
      was also performed. Superinduction including intratumoral injection of cationic
      liposomes containing polyI:polyC resulted in growth inhibition of U251-NN tumors
      and eradication of U251-SP tumors. Weight gain in mice was not inhibited by
      modified superinduction. Cationic liposomes decreased drug toxicity, and may help
      to target tumor cells in the modified superinduction of endogenous HuIFN-beta
      production.

PMID- 9780645
TI  - Speech arrest caused by meningioma--two case reports.
AB  - Parasagittal or falx meningioma occasionally causes paroxysmal speech
      disturbance. A 22-year-old and a 46-year-old female harboring meningiomas
      suffered recurrent episodes of supplementary motor seizures. Magnetic resonance
      imaging showed the meningioma compressing the left supplementary motor area.
      Seizures did not recur after total removal of the tumors.

PMID- 9780646
TI  - Multiple dural arteriovenous fistulas.
AB  - Four patients with multiple intracranial dural arteriovenous fistulas (DAVFs) at
      separate sites were treated by endovascular techniques (transarterial and/or
      transvenous embolization), surgery (excision or isolation), radiotherapy, or
      combinations, according to the pathophysiological condition. All lesions in two
      patients were obliterated completely without neurological deficit. There were
      residual fistulas after the treatment in two patients, but these were low-grade
      lesions without retrograde cortical venous drainage, and marked clinical
      improvement was obtained. Planning of treatment strategies for multiple DAVFs
      requires careful analysis of the venous drainage from the affected sinuses and
      cerebral hemodynamics.

PMID- 9780647
TI  - Anterior communicating artery aneurysm associated with tuberculum sellae
      meningioma--case report.
AB  - A 50-year-old male presented with a very unusual case of a calcified anterior
      communicating artery (AComA) aneurysm associated with a tuberculum sellae
      meningioma. Until 10 years previously, the patient had been a professional soccer
      player for 15 years. He noticed a slight decrease in visual acuity in the right
      eye 7 years before. The patient was in the care of an oculist throughout this
      period. Two months before admission, a significant and rapid decrease of vision
      in the right eye occurred. Computed tomography and magnetic resonance imaging
      showed a round-shaped, partially calcified tumorous lesion. Four-vessel
      angiography revealed a large AComA aneurysm. During surgery, a tuberculum sellae.
      meningioma was found in combination with an AComA aneurysm with a completely
      calcified wall. The meningioma was resected totally. The AComA aneurysm with a
      calcified wall could not be clipped or resected and was left alone. His visual
      deficit improved postoperatively.

PMID- 9780649
TI  - Giant pyocele in the anterior intracranial fossa--case report.
AB  - A 43-year-old male presented with headache localized in the right forehead.
      Computed tomography and magnetic resonance imaging demonstrated a cystic mass in
      the frontal sinus, with a huge extension into the anterior cranial fossa. The
      mass was removed by transcranial surgery. The cyst contained pus. Histological
      examination of the cyst wall revealed mucocele (pyocele). Pyocele with huge
      intracranial extension is rare and requires combined neurosurgery and
      otolaryngology for optimum treatment.

PMID- 9780648
TI  - Intramedullary hemangioblastoma of the medulla oblongata--two case reports and
      review of the literature.
AB  - We determined the treatment modality of hemangioblastoma of the brain stem on the
      bases of our two cases and 31 cases searching from the literature since 1960
      which were treated surgically. Hemangioblastomas of the brain stem were
      categorized according to one of three locations: hemangioblastoma of the fourth
      ventricle attached to the floor of the ventricle (Type A), hemangioblastoma of
      the fourth ventricle partially embedded in the floor of the ventricle (Type E),
      and intramedullary hemangioblastoma of the medulla oblongata (Type I); and were
      evaluated their clinical features including the operative mortality and morbidity
      of each location. In our two cases of Type I hemangioblastoma, Case 1, removed
      partially, died due to sleep apnea and Case 2 lead to normal school life after
      hemangioblastomas were removed radically. In our review of the 33 surgically
      treated cases, radical excision was carried out in 29 cases (87.9%). The
      mortality was 24.2% overall; that of Type A was 25%, Type E was 28.6%, and Type I
      was 14.3%. In terms of postoperative mortality, the location of the
      hemangioblastoma was irrelevant and radical excision was much better than partial
      removal. Hemangioblastomas of the brain stem could be removed radically by
      meticulous dissection of the tumor on distinct cleavage, even in cases of
      intramedullary location. Microsurgical dissection of medullary hemangioblastomas
      with low morbidity is feasible and prudent postoperative care is mandatory to
      reduce the operative mortality and morbidity.

PMID- 9780650
TI  - Two-staged resection of a left frontal astrocytoma involving the operculum and
      insula using intraoperative neurophysiological monitoring--case report.
AB  - A 29-year-old right-handed male with a 12-year education presented with a 2-month
      history of generalized epileptic activity. Neuroradiological imaging demonstrated
      a large lesion in the left frontal lobe involving the insulooperculum and in the
      temporal tip. Neurological and neuropsychological examination revealed no
      abnormality. Two-staged total resection of a left frontal large astrocytoma
      involving the insulooperculum was achieved, with preservation of the speech and
      motor functions. The prefrontal area was resected en bloc under general
      anesthesia. To avoid vascular damage including the lenticulostriate arteries, the
      sylvian and the interhemispheric fissures were thoroughly opened. The tumor was
      apparently located in the anatomical Broca's area. Eighteen days later, the
      residual tumor was totally resected with no language deficit after identifying
      the motor-speech cortex, which was displaced from the usual location, by direct
      cortical stimulation under local anesthesia. The medially extended insular tumor
      was then resected stepwise with frequent neurological monitoring with the patient
      awake. Surgery for intraaxial insuloopercular lesions in the dominant hemisphere
      carries a high risk of speech and motor deficit. This staged operation enables
      maximum tumor resection of dominant-side large frontal gliomas involving the
      insuloopercular region, with preservation of both motor and speech functions.

PMID- 9780652
TI  - [Characterization of phenolic glycolipid-I (PGL-I) like antigen in renal cell
      carcinoma].
AB  - BACKGROUND: We investigated whether phenolic glycolipid-I (PGL-I) produced by
      Mycobacterium leprae (M. leprae), can be used as a marker of renal tumors.
      METHODS: Using a preparted anti-PGL-I monoclonal antibody (SF-I), anti-PGL-I
      group antibodies and PGL-I group antigens were detected and PGL-I
      immunohistologic staining were performed. RESULTS: The titer of anti-PGL-I
      antibody in patients with renal cell carcinoma was 0.283 +/- 0.103, showing a
      trend of rising titer of anti-PGL-I group antibody with higher cytologic atypia.
      When compared by the extent of tumor infiltration, a high antibody titer was
      observed in stage 4 infiltration group. Regarding the PGL-I group antigen that
      was detected using SF-1 in the urine of patients with renal cell carcinoma, no
      relationships between the positive rte of the antigens with common antigenicity
      to PGL-I and the grade of carcinoma were observed. However, in terms of the
      extent of tumor infiltration, a trend that the positive rate for PGL-I group
      antigen increased with the progression of cancer stage was seen. The Western blot
      assay of the urine of patients with renal cell carcinoma following
      electrophoresis revealed a change around 40 KD. The immunohistologic stains with
      SF-1 disclosed a predominance in the proximal kidney tubule. CONCLUSION: Using
      PGL-I group antigen and PGL-I group antibody as markers of renal cell carcinoma,
      a rapid and precise measurement may be provided.

PMID- 9780651
TI  - Primitive neuroectodermal tumor in the spinal epidural space--case report.
AB  - A 4-year-old boy presented with a rare case of an epidural tumor causing
      compression of the thoracic spinal cord manifesting as rapid worsening of gait
      disturbance. The tumor was grossly totally resected, and radiotherapy and
      chemotherapy were subsequently administered. The histological diagnosis was
      primitive neuroectodermal tumor. He has been free of recurrence for more than 6
      years. Early tumor resection followed by chemotherapy and irradiation is
      recommended for patients with primitive neuroectodermal tumor and unstable
      symptoms.

PMID- 9780654
TI  - [The results of a long-term follow-up for patients with stage Ta bladder cancer,
      especially regarding those with multiple recurrences].
AB  - OBJECTIVE: We reviewed our series of stage Ta bladder cancer patients with a long
      term follow-up in order to clarify the prognosis of these patients, especially
      those who have repeated recurrences. MATERIALS AND METHODS: A retrospective study
      was done on 88 patients with stage Ta bladder cancer who were treated between
      1971 and 1990 at our hospital. All patients reviewed were followed up for at
      least 5 years. RESULTS: Fifty-three patients out of 88 had recurrence, and the
      number of recurrences ranged from one to eleven. In the first recurrence, the 5-
      and 10-year recurrence-free rates were 53.4% and 37.1%, respectively. In the
      second recurrence, those rates were 25.7% and 15.9%, respectively. Comparisons of
      the recurrence-free rates between the first recurrence and that of more than 2
      times yielded statistically significance (p < 0.01). On the other hand, when the
      recurrence-free rates of those patients showing recurrence more than 2 times were
      compared no statistical significance was observed among them. In addition, most
      patients with multiple recurrences also tended to show a long tumor-free period
      at some point. In eight patients a stage-up of > or = T1 developed during the
      study period. No characteristics of the tumors, including the multiplicity of the
      recurrence, was found to correlate with the stage-up. CONCLUSIONS: Most patients
      with multiple recurrences demonstrated a long tumor-free period at some point,
      and, moreover, in some of those patients there was also a possibility that no
      further recurrence occurred. In addition, frequent recurrence was not associated
      with increased incidence of stage-up. Based on these findings, multiple
      recurrence is not thought to be an especially ominous sign, and therefore bladder
      preserving therapy is indicated for such patients.

PMID- 9780653
TI  - [Clinical study of carcinoma in situ of the urinary bladder].
AB  - PURPOSE: To evaluate the natural history and the efficacy of treatments for
      carcinoma in situ (CIS) of the urinary bladder, we reviewed 70 patients with this
      disease. METHOD: The patients of CIS were divided into 3 groups based on tumor
      history: primary, secondary and concurrent CIS. We studied 70 patients with
      primary and secondary CIS treated at our hospital between 1957 and 1995,
      exclusive of concurrent one. They included 31 patients with primary CIS and 39
      with secondary one, ranging in age from 39 to 82, with the average age of 63.1
      years. Sixty-one patients were male and 9 were female. RESULTS: In 31 patients
      with primary CIS, 12 (32.8%) complained of gross hematuria, 10 (32.3%) urinary
      frequency and 9 (29.0%) pain on urination. The 5-year survival rates for primary
      and secondary CIS were 89.1% and 91.4%, and the 5-year bladder preservation rates
      were 54.5% and 57.6%, respectively. Three of 31 patients with primary CIS
      developed an invasive carcinoma, whereas 4 of 39 patients with secondary CIS did.
      There was no significant difference between each primary and secondary groups. In
      both primary and secondary CIS, the group of immediate total cystectomy was not
      significantly differ from the groups of the following total cystectomy and the
      bladder preservation in the effect of total cystectomy on the survival rate. A
      total of 51 cases of CIS was treated with intravesical therapy, 17 intravesical
      Bacillus Calmette-Guerin (BCG) therapy, 34 intravesical chemotherapy,
      respectively. Intravesical BCG therapy has shown the complete response rate of
      78.6%, intravesical chemotherapy 42.1%. And the bladder preservation rate seemed
      to be better (but not significantly) in intravesical BCG group than in
      intravesical chemotherapy group or non-treatment group of intravesical therapy.
      CONCLUSION: For both primary and secondary CIS, the 5-year survival rate was
      about 90% and 5-year bladder preservation rate was over 50%. There was no
      significant difference between the primary and secondary group. The group of
      immediate total cystectomy was not significantly differ from the groups of the
      following total cystectomy and the bladder preservation in the effect of total
      cystectomy on the survival rate. About intravesical therapy, BCG was very
      effective in CR rate and the bladder preservation rate seemed to be better (but
      not significantly) in BCG group than in chemotherapy or non-treatment group.

PMID- 9780655
TI  - [Clinical background and treatment of brain metastasis from renal cell
      carcinoma].
AB  - OBJECTIVE: The objective of this study is to evaluate the clinicopathological
      characteristics and the effect of therapy of brain metastasis from renal cell
      carcinoma. METHOD: Of 306 cases with renal cell carcinoma treated at Keio
      University Hospital from June, 1976 to May, 1996, 20 (6.5%) developed brain
      metastasis. Metastasis-free rate and survival rate were evaluated by Kaplan
      Meier's method and tested statistically with Long-rank test. RESULT: As for the
      time of the brain metastasis, it was already at the time of initial diagnosis in
      6 cases, and in the other 14, it was after the diagnosis of original disease. The
      average interval between the diagnosis of original disease and metastasis was
      53.9 months. Only 2 cases have no metastasis without brain, and 17 of 20 cases
      (85.0%) were complicated by pulmonary metastasis and 10 (50.0%) by bone
      metastasis. It was considered that the brain metastasis was accompanied with
      other metastases. As for the treatment, cytokine therapy was performed on 18
      cases without efficacy. It was supposed that in cases with pulmonary metastasis,
      IL-2 therapy may have the possibility of increasing the frequency of brain
      metastasis. 9 of 20 cases were subjected to surgical treatment with significantly
      better prognosis than the cases without the operation. Two cases were long-term
      survivors more than 5 years after the diagnosis of brain metastasis and both
      underwent surgical treatment to brain metastasis. CONCLUSION: Cytokine therapy
      was not effective to brain metastasis from renal cell carcinoma. On the other
      hand, however, it was suggested that surgical treatment could improve prognosis
      if the metastatic lesions could be resected.

PMID- 9780656
TI  - [Usefulness of micronucleus assay in radiosensitivity tests using human cancer
      cell lines].
AB  - BACKGROUND: Recently, micronucleus assay is expected to be one of the
      radiosensitivity tests. The usefulness of micronucleus assay was compared with
      MTT assay and clonogenic assay using 5 human derived urological cancer cell
      lines, NBT-2, T24, PC3, OS-RC-2, and RERF-LC-AI in vitro. The correlation between
      the results in vitro assay and the radiation effects of nude mouse in vivo was
      investigated. METHODS: In vitro, the micronucleus frequency of 2 Gy radiation was
      scored in micronucleus assay. The survival fraction of 2 Gy radiation was
      obtained in MTT assay and clonogenic assay. The correlation between 3 assays was
      investigated. In vivo, cancer cells was inoculated to nude mouse and the tumor
      volume was measured at 3-7 days interval in control group and 10 Gy irradiated
      group. The tumor volume ratio in irradiated group to control group was calculated
      as a radiation effect in each cell lines, the correlation between this ratio in
      vivo and each value of 2 Gy radiation in vitro was studied. RESULTS: The
      correlation between micronucleus frequency and survival fraction in clonogenic
      assay was statistically significant (r = 0.941, p = 0.0169). But the correlation
      of the survival fraction between MTT assay and clonogenic assay is not
      statistically significant. The correlation between micronucleus frequency and the
      tumor volume ratio in vivo was statistically significant (r = 0.990, p = 0.0011).
      The correlation between survival fraction in clonogenic assay and the tumor
      volume ratio in vivo was also statistically significant (r = 0.914, p = 0.0298).
      However, the correlation between survival fraction in MTT assay and the tumor
      volume ratio in vivo was not statistically significant (r = 0.782, p = 0.118).
      CONCLUSION: In this 5 cell lines, micronucleus assay was most correlated to nude
      mouse radiation effect. This result suggested the possibility of micronucleus
      assay to be a better predictive method than clonogenic assay for radiosensitivity
      test.

PMID- 9780657
TI  - [Significance of lymphadenectomy in renal cancer].
AB  - BACKGROUND AND OBJECTIVE: Clinical significance and indication for
      lymphadenectomy (LND) in renal cancer are controversial. In this study, we
      investigated renal cancer patients to clarify practical indications for LND.
      MATERIALS AND METHODS: We retrospectively investigated lymph node metastasis in
      238 renal cancer patients nephrectomized between September 1987 and November 1996
      at Niigata University and related hospitals, especially concerning distant
      metastasis and clinical (pre- and/or intra-operative) diagnosis for lymph
      adenopathy, which could be detected before histopathological examination.
      Survival curves were drawn according to Kaplan-Meier's method, and statistic
      analyses were performed with chi-square test (or Fisher's exact test), Cox's
      multivariate proportional hazard test, Log-Rank test and t-test. RESULTS: One
      hundred and eighty seven of 238 patients (78.6%) were lymphadenectomized, and in
      another five patients lymph node dissection was incomplete. Eighteen of 192
      patients (9.4%) were revealed to have positive nodes (pN+), which were frequently
      accompanied with advanced stage, distant metastasis, high grade, large tumor and
      poor survival compared to pN0. Clinical diagnosis for lymph node metastasis
      showed 57% of positive predictive value (13 of 23 patients which were expected to
      have positive nodes (cN+)). All of three false negative cases (2.1% of 142 cN0)
      had large tumor. cN+ and pN+ were frequently accompanied with increased CRP
      and/or fever up. Interferon-alpha was effective for two patients to suppress
      enlargement of newly appeared lymph adenopathy, and not effective for other seven
      patients with residual or recurrent nodes. CONCLUSION: pN+ was frequently
      accompanied with advanced stage and poor prognosis, which suggested diagnostic
      and prognostic significance of LND. It was considered that therapeutic LND is
      indicated for the patients with enlarged lymph nodes or large tumor without
      distant metastases, and for the patients with both enlarged lymph nodes and
      distant metastases which seem to be slowly progressing and probably curable.

PMID- 9780658
TI  - [Bilateral pheochromocytomas with von Hippel-Lindau's disease: a case report].
AB  - A case of bilateral pheochromocytomas with von Hippel-Lindau's disease (VHL) is
      reported. A 46-year-old woman who had hyperglycemia was admitted to our hospital
      because of abdominal tumors. Her elder sister and niece had been diagnosed as
      VHL. Ultrasonography, CT, and MRI revealed bilateral adrenal tumors.
      Noradrenaline levels in serum and urine were elevated and 131I-MIBG scintigraphy
      showed accumulation in bilateral adrenal glands. Moreover, she had bilateral
      renal cysts and cerebellar hemangioblastoma. Bilateral adrenalectomies were
      performed and pathological diagnosis was pheochromocytoma. This is the seventh
      case of bilateral pheochromocytomas with VHL reported in Japan.

PMID- 9780659
TI  - [The growing teratoma syndrome: report of a case].
AB  - A 32-year-old man presented with a swelling of the left testis, for which he
      underwent high inguinal orchiectomy. Histopathological examination of the
      specimen revealed teratocarcinoma. Further evaluation revealed no metastasis
      (stage I), and he was followed-up by monthly examination without prophylactic
      chemotherapy (surveillance). Thirteen months after orchiectomy, AFP and hCG-beta
      were elevated at 133.8 ng/ml and 0.8 ng/ml respectively. Abdominal CT scan
      revealed para-aortic masses of recurrent tumor. Although the AFP and hCG-beta
      levels markedly declined after five courses of COMPE (CDDP, VCR, MTX, PEP,
      Etoposide) chemotherapy, the retroperitoneal masses had further enlarged and had
      undergone cystic change. Excision of the residual tumors was performed, and
      microscopic examination of specimens revealed mature teratoma without malignant
      components. The diagnosis of the growing teratoma syndrome was therefore made.
      The growing teratoma syndrome occurs in nonseminomatous testicular germ cell
      tumors following chemotherapy and is characterized by enlargement of metastatic
      lesions with normal tumor marker levels. Total surgical resection of the mass
      yields good results, and tumor is unresponsive to chemotherapy. Early recognition
      of this syndrome is important for successful treatment.

PMID- 9780660
TI  - [Metastatic renal tumor of malignant salignant salivary-gland-like tumor of the
      lung: A case report].
AB  - A 17-year-old woman was admitted to our hospital for the investigation of
      asymptomatic gross hematuria. Twenty nine months ago, she had received the right
      lower lobectomy because of the malignant salivary gland type mixed tumor of the
      bronchus. The intravenous pyelography and the right retrograde pyelography showed
      the irregular wall of the right renal pelvis. The computerized tomography showed
      a hypodense tumor which occupied the lower half of the right kidney. Cystoscopy
      showed bleeding from the right ureteral orifice. Chest X-ray revealed multiple
      lung metastases at the first examination, but right nephrectomy was performed
      because gross hematuria continued. The tumor thrombus, which spreaded into vena
      cava, was removed. The pathological diagnosis was the metastatic renal tumor of
      malignant salivary gland type mixed tumor. The patient died 102 days
      postoperatively.

PMID- 9780661
TI  - Changes in brain barbiturate concentration in brain-dead rabbits.
AB  - Pentobarbital concentration was evaluated in the brain tissues of brain-dead
      rabbits. Pentobarbital was infused into the vein of Japanese white male rabbits
      at 60 mg/kg/h until an isoelectric EEG of the cortex was reached. Brain death was
      induced by inflation of a balloon catheter placed in the subdural space. The
      diagnosis of brain death was confirmed by a flat line ABR wave. A significant
      increase in heart rate, intracranial pressure, and mean arterial pressure, was
      observed following brain death induction. These parameters returned to below
      basal values within 60 mm. Immediately after, and at 6 h and 24 h after brain
      death, each group of rabbits was sacrificed by phenobarbital overdose, and brains
      were then removed for determination of pentobarbital concentration in the brain
      tissue. Blood pentobarbital disappeared about 18 h after brain death was induced.
      Although the brain pentobarbital concentration slightly decreased over time, a
      high concentration of pentobarbital remained in the brain 24 h after brain death
      was induced.

PMID- 9780662
TI  - [Typing of DNA using the primer extension preamplification (PEP) method--studies
      of reliability of typing and detection limits].
AB  - Primer extension preamplification (PEP), which can amplify sequence-independently
      a limited quantity of DNA as a whole, allows multiple DNA analyses by polymerase
      chain reaction (PCR). This technique may be applicable to forensic cases,
      especially in cases where only small amounts of DNA are available. To define the
      accuracy and sensitivity of PEP, the DNA typing results of nine loci (TH01,
      MCT118, HLA-DQ alpha, amelogenin, LDLR, GYPA, HBGG, D7S8, GC) by PCR with PEP
      (PEP-PCR) were compared with those by PCR without PEP. Both results were
      identical to each other for each sample tested. Furthermore, amplification of an
      initial genomic DNA by PEP was found to range from 15 to 600 times of the initial
      quantity and the efficiency of PEP may depend on the sequences flanking the loci
      tested. These results indicate that PEP can increase typing potential of PCR from
      forensic samples.

PMID- 9780663
TI  - [Simple determination methods for blood grouping from biological stains. 2.
      Immunochromatographic determination of ABO blood groups from saliva specimens].
AB  - A simple immunochromatographic method was used to determine ABO blood groups and
      secretor status from saliva stains. Saliva specimens were serially diluted with
      PBS and dotted onto nitrocellulose strips (10 mm x 70-100 mm). One end of the
      strips was dipped in two drops of 0.1% orange-red gold particles (GP) which were
      coated with an anti-A, anti-B or anti-H blood group reagent. The GP migrated
      along the surface of the strips producing red spots where positive antigen
      antibody reactions occurred. In non-secretors, the end-points of saliva dilution
      were lower than in secretors. The results of this test were obtained within 2 to
      3 minutes. Moreover, the GP reagents utilized were quite inexpensive. The
      principles underlying this method might be useful in species and organ
      identification.

PMID- 9780664
TI  - [Use of a CO-oximeter for forensic diagnosis of hypothermia].
AB  - Blood samples were collected from the right and left atria separately in 9 cases
      of hypothermia and 18 cases of non-hypothermia during judicial and consented
      autopsy between March 1995 and December 1997. The oxyhemoglobin ratio (O2Hb),
      reduced hemoglobin ratio (RHb) and oxygen saturation (sO2) were measured by
      oximetric analysis. O2Hb, R-Hb and sO2 were significantly greater in the
      hypothermic group than the non-hypothermic group. We conclude that the diagnosis
      of hypothermia can be established in cases where O2Hb and sO2 in the left atrium
      exceed 80%, irrespective of values in the right atrium.

PMID- 9780665
TI  - Simple methods of forced oral opening for cadavers oriented to causes of fixed
      jaw.
AB  - Forensic dentistry plays an essential role in personal identification procedures.
      An adequate interincisal space of relatively fresh cadavers would be required to
      obtain detailed dental findings. We developed novel and simple procedures of oral
      opening which are oriented to the causes of the fixed jaw and conscious of facial
      damage. Preliminary inspection disclosed three causes of the difficulty of oral
      opening, namely exceptional drying or parchmenting, rigor mortis and loss of
      extensibility of the temporalis muscles. Tenotomy on the temporalis muscles for
      cases with the last two factors, and/or mandibular periosteal stripping for those
      with the first one were employed to approach the oral cavity of cadavers, and a
      desired degree of interincisal opening was attained. Single or combinational
      operation of these methods is definitely effective to obtain odontological data
      without altering facial configuration.

PMID- 9780666
TI  - An autopsy case of unusual massive gastrointestinal hemorrhaging.
AB  - An autopsy case is presented involving massive gastrointestinal hemorrhaging. A
      58-year-old woman was found dead with bloody patches on her body. An autopsy
      revealed a lacerated wound to the mucosa of the stomach and a sharp fish bone was
      found among bloody contents within the stomach. The duodenum and small intestines
      contained abundant tarry contents, but the mucosa of the intestinal tract was
      intact. The cause of death was certified as hemorrhagic shock due to massive
      bleeding from a wound to the gastric mucosa inflicted by a sharp fish bone.
      Therefore the possibility that some foreign body has been swallowed must be
      considered when forensic pathologists investigate cases with bleeding of unknown
      origin from the alimentary tract.

PMID- 9780667
TI  - Sudden death of a patient with Crohn's disease.
AB  - We describe a case of sudden death caused by a rare complication of Crohn's
      disease. A 29-year-old man with Crohn's disease who had not taken medications
      regularly complained of nausea, vomiting, and abdominal pain for 2 days, and then
      died suddenly. Autopsy revealed protruding intestinal loops filled with gas,
      internal fistulas between fused loops of the terminal ileum, and complete
      obstruction of the fistulous tract. The histologic findings of transmural
      inflammation consisting of lymphocytic infiltration, accumulation of partially
      hyalinized collagen, and fibrosis in the skip areas from the ileum to the cecum
      were compatible with Crohn's disease. Furthermore, marked emaciation, atrophic
      change of the heart muscle, and diffuse fatty change of the liver were found.
      Although the patient died of obstructive ileus caused by a stricture produced by
      progression of Crohn's disease, he was severely affected by malnutrition which
      may have been fatal. This case not only illustrates that Crohn's disease can
      cause obstructive ileus and sudden death, but also makes the forensic pathologist
      realize the importance of suspecting the presence of an active inflammatory bowel
      disease in a patient with internal fistulas or malnutrition.

PMID- 9780668
TI  - Sudden infant death from aspiration of milk due to superior cornual defect of
      thyroid cartilage.
AB  - An autopsy case of a 4-month-old boy who died immediately after being fed by a
      member of the staff of a day-care centre is described in this report. An autopsy
      certified that the cause of death was the aspiration of milk. There was no other
      apparent reason for the aspiration of milk into the trachea except for the left
      superior cornual defect of the thyroid cartilage. We therefore conclude that it
      was this defect which led to the aspiration of milk into the trachea.

PMID- 9780669
TI  - [Difficulty of getting correct dental findings for a doctor of medicine:
      deciduous molars found in a 16-year-old female].
AB  - The first victim of four serial murders occurring in Hiroshima in 1996 was an
      unidentified young female when she was found. In the lower jaw, the left and
      right deciduous second molars were identified, and the left and right permanent
      second premolars were revealed to be congenitally defective by X-ray examination.
      Comparison of the dental findings and study model after death with those before
      death identified the victim as a 16-year old female.

PMID- 9780670
TI  - [Characteristics of hematopoietic stem cells].

PMID- 9780671
TI  - [Current status of hematopoietic stem cell transplantation].

PMID- 9780672
TI  - [Indication and results of hematopoietic stem cell transplantation. 1. Acute
      leukemia].

PMID- 9780673
TI  - [Indication and results of hematopoietic stem cell transplantation. 2. Chronic
      myelogenous leukemia].

PMID- 9780674
TI  - [Indication and results of hematopoietic stem cell transplantation. 3. Aplastic
      anemia and myelodysplastic syndrome].

PMID- 9780675
TI  - [Indication and results of hematopoietic stem cell transplantation. 4. Malignant
      lymphoma and multiple myeloma].

PMID- 9780676
TI  - [Indication and results of hematopoietic stem cell transplantation. 5. Solid
      tumor].

PMID- 9780677
TI  - [Complications of hematopoietic stem cell transplantation: physiopathology and
      management. 1. Infections].

PMID- 9780678
TI  - [Complications of hematopoietic stem cell transplantation: physiopathology and
      management. 2. Graft-versus-host disease (GVHD)].

PMID- 9780679
TI  - [Bone marrow banks and transplantation of bone marrow from unrelated donors].

PMID- 9780680
TI  - [Development in cord blood transplantation].

PMID- 9780681
TI  - [Donor coordination at bone marrow banks and the role of coordinators].

PMID- 9780682
TI  - [Gene transfer to hematopoietic stem cells and its clinical application].

PMID- 9780683
TI  - [Future development in hematopoietic stem cell transplantation. Discussion].

PMID- 9780685
TI  - [Case of paroxysmal nocturnal hemoglobinuria diagnosed by the analysis of
      leukocyte glycosylphosphatidylinositol protein].

PMID- 9780684
TI  - [Case of systemic erythematodes on long-term care with repeated development of
      severe cytomegalovirus infection].

PMID- 9780686
TI  - [IgD-type multiple myeloma with confirmation of improvement in renal pathology
      achieved by chemotherapy].

PMID- 9780687
TI  - [Case of eosinophilic gastroenteritis complicated with eosinophilic cholecysto
      cholangitis].

PMID- 9780688
TI  - [Patients confined in bed for an extended period and developing cholinergic
      crisis following administration of distigmine bromide: report of 3 cases].

PMID- 9780689
TI  - [Fc receptor redux: the role of immunoglobulin receptor (FcR) in
      glomerulonephritis].

PMID- 9780691
TI  - [Defense mechanism of the myocardium].

PMID- 9780690
TI  - [Neovascularization and tumor development].

PMID- 9780692
TI  - [TH1/TH2 balance in chronic rheumatoid arthritis].

PMID- 9780693
TI  - [Case of chronic renal tubular interstitial nephritis with syndrome of
      disappearing bile ducts].

PMID- 9780696
TI  - [Molecular aspect of gastroduodenal ulcer healing].

PMID- 9780695
TI  - [The mechanisms of gastrointestinal mucosal injury and repair].
AB  - Peptic ulcer disease are usually accompanied by diffuse inflammation over the
      gastroduodenal mucosa in addition to severe local inflammation at the site of
      ulceration. It is well known that inflammatory cytokine are the main mediators of
      inflammation. Cytokines may also play a part in acute gastroduodenal mucosal
      lesions (AGML) caused by NSAID, H. pylori, and stress. Among cytokines most
      involved in AGML, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL) 1, IL
      6, and IL-8 modulate chemotaxis, chemokinetics, and aggregation and release of
      lysosomal enzymes from neutrophils. Ulcer healing requires interaction of various
      cellular and connective tissue components. The stimulus for increased cell
      proliferation is most likely initiated by EGF and/or TGF-alpha which are
      mitogenic peptides for gastric epithelial cell at the initial stage in ulcer
      healing after ulcer induction. Transforming growth factor-beta (TGF-beta) also
      potentially involved in the ulcer healing process. During the chronic stage of
      ulceration, the growth of granulation tissue and generation of new microvessels
      by angiogenesis is stimulated by the fibroblast growth factors, platelet derived
      growth factor, TGF-beta, prostaglandins and/or IL-1 and TNF-alpha. The quality of
      mucosal restoration may be the most important factor in determining whether
      ulcers will recur. The proper restoration of the mucosal architecture requires
      balanced stimulation and interaction of both epithelial and connective tissue
      components, as well as, activation of growth factors which controls these
      components.

PMID- 9780697
TI  - [Mucosal immune system of the intestine].
AB  - Gut-associated lymphoid tissue is the major inductive site of mucosal immune
      system, functionally independent of the systemic immune system. Particulate
      antigens are mainly uptaken from M cell of Peyer's patches, inducing IgA
      production in the intestinal mucosa. Lymphocytes are continuously recirculating
      through the intestinal mucosa to facilitate intestinal immune response.
      Dysregulation of lymphocyte migration and cytokine imbalance in the intestinal
      mucosa may be largely involved in the pathogenesis of inflammatory bowel diseases
      including intestinal allergy and Crohn's disease. There is also a possibility
      that dietary components especially long chain fatty acid could influence immune
      cell function of the intestinal mucosa. Because dietary components are closely
      associated with immunological function of intestinal mucosa, the importance of
      dietary manipulation for the management of inflammatory bowel diseases should be
      concerned.

PMID- 9780698
TI  - [Cytokines and gut].
AB  - Cytokines are soluble proteins or glycoproteins produced by a wide variety of
      cell types. Cytokines are local regulatory factors which are involved in cell
      growth, cell differentiation, inflammation, and immune responses. In the
      gastrointestinal mucosa, not only inflammatory cells but also epithelial and
      mesenchymal cells secrete cytokines in response to various stimuli. Inflammatory
      cytokines are playing critical roles in the inflammation associated with
      gastrointestinal infections, including Helicobacter pylori infection in the
      gastric mucosa. Animal studies have shown that abnormal cytokine response may be
      risk for developing inflammatory bowel diseases, such as ulcerative colitis and
      Crohn's disease. Cytokines will be important therapeutic targets in these
      diseases.

PMID- 9780699
TI  - [Neutrophil-endothelial cell interactions in gastrointestinal diseases].
AB  - The adherence of neutrophils to the endothelium is a crucial early event in the
      inflammatory and immunological reaction. Neutrophil-endothelial cell interactions
      are known to be mediated by adhesion molecules that are expressed on each cell.
      Among the adhesion molecules expressed on leukocytes, the CD11/CD18 integrin
      family plays a major role in the adhesion and transendothelial migration of
      neutrophils. The two most extensively characterized endothelial cell adhesion
      molecules are intercellular adhesion molecule-1 and E-selectin. These adhesion
      molecules are involved in the pathogenesis of several digestive diseases such as
      Helicobacter pylori, non steroidal anti inflammatory drug- or stress-induced
      gastric mucosal injury, inflammatory bowel diseases.

PMID- 9780700
TI  - [Mucosal microcirculation and angiogenesis in gastrointestinal tract].
AB  - In this review, various aspects of gastrointestinal microcirculation were
      described. Endothelin-1, vasoconstrictor, is elevated in gastric mucosa, causes
      gastric ischemia and results in gastric ulceration in human and animals under
      physical stress. Vasodilators such as NO anticipate the alove actions of
      endothelin, and thereby protect mucosa from injury. Once ulcer is developed,
      angiogenesis plays a key role in its healing. Various growth factors,
      cyclooxygenases-1 and -2, and non-peptide angiogenic factors stimulate this
      phenomenon and participate in ulcer healing. However, acidic conditions, H.
      pylori and its product, ammonia, suppress angiogenesis in vitro and in vivo.
      These evidences may explain why ulcer heals so slowly in gastroduodenal mucosa.

PMID- 9780701
TI  - [Factors involved in the regeneration of the gastrointestinal tract].
AB  - The gastrointestinal mucosal regeneration is a complex process that includes cell
      migration and proliferation. A wide variety of factors are presumably be involved
      in the reestablishment of the functional and structural integrity of the mucosa,
      and different experimental models have been applied to elucidate these factors.
      Accumulating evidences indicate the importance of soluble factors (e.g. growth
      factors, cytokines, trefoil peptides) and matrix components in the mucosal
      healing. Though the interactions of these factors remain to be fully elucidated,
      the identification of physiologically relevant factors that stimulate mucosal
      repair and a through description of the mechanisms of action may lead to the
      development of specific strategy for the promotion of the mucosal healing by
      exploiting natural mechanisms of regeneration.

PMID- 9780702
TI  - [Gastrointestinal motility in hemorrhagic gastrointestinal diseases].

PMID- 9780703
TI  - [Peptic ulcer disease and hemorrhagic gastritis with H. pylori infection].
AB  - Most of gastroduodenal diseases are associated with Helicobacter pylori
      infection. Cure of H. pylori infection may lead complete remission of recurrence
      of gastric and duodenal ulcer, and suppress the development of atrophic
      gastritis, gastric cancer and MALT lymphoma. H. pylori infection and hemorrhagic
      gastroduodenal diseases are reviewed.

PMID- 9780705
TI  - [Endoscopic hemostasis for esophagogastric bleeding: technical assessment and
      recent advances].
AB  - The method and its technical issues of endoscopic hemostasis for the upper gastro
      intestinal bleeding were reviewed. Precise diagnosis of bleeding point by
      endoscopic observation has become almost perfect with the technological progress
      of endoscopy. For large veins such as esophagogastric varices, endoscopic
      sclerotherapy has achieved great success. For small protruded vessels such as
      small arteries, mechanical method like clipping or band-ligation has advantage.
      Chemical or physical coagulation is also very useful for hemostasis of small
      vessels. Combination of two or three methods is sometimes effective in
      complicated patients. Endoscopic hemostasis is now golden standard for
      gastrointestinal hemorrhage.

PMID- 9780704
TI  - [Ethanol-induced injury and GI bleeding].
AB  - Ethanol-induced injury of digestive organs closely linked to the GI bleeding. The
      gastric or esophageal mucosal hemorrhage evoked by extra-amounts of alcohols is
      initiated by the microcirculatory damage of gastrointestinal mucosa. Many
      investigators focused on the ethanol-induced gastric ulcer formation as well as
      the ethanol-induced gastroesophageal reflux injury. Although the most important
      treatment for such a damage is of course to stop the drinking, it is also
      important to protect the gastrointestinal mucosa by potentiate the mucosal
      defense systems.

PMID- 9780706
TI  - [Angiographic diagnosis and management of bleeding from the digestive organs].
AB  - Gastrointestinal bleeding is recently seen less often by the angiographer. This
      is mainly due to advances in endoscopy, and nuclear medicine. When patients with
      gastrointestinal bleeding are referred, endoscopic diagnosis and therapy should
      be performed at first. However, when it is impossible to diagnose or to control
      the bleeding, angiography must be considered as soon as possible. Intra-abdominal
      bleeding should be diagnosed by angiography at first. In both cases, embolization
      is generally safe and effective depending on the advance of occlusive agents.

PMID- 9780707
TI  - [Application of ultrasound method for hemorrhagic digestive disease].
AB  - Ultrasonography for the digestive diseases are consisted of abdominal
      ultrasonography (US), endoscopic ultrasonography (EUS) and color Doppler
      endoscopic ultrasonography (CDEUS). These play a supplementary role in comparison
      with the roentgenography and endoscopy. The information of the ultrasonography is
      different from these examinations. By US the collateral shunts of esophago
      gastric varices are observed. EUS is useful for diagnosis of the properties of
      esophago-gastric varices and judgement of effects of treatment for these varices,
      gastric ulcer and vessels in ulcer base and hemorrhagic bowel diseases. CDEUS can
      show blood streams of esophago-gastric varices and hemorrhagic ulcer.

PMID- 9780708
TI  - [Recent progress in the drug therapy for gastrointestinal bleeding].
AB  - Progress in drug therapy, endoscopic hemostasis and interventional radiology
      reduced the number of surgical operation for gastrointestinal bleeding. In the
      upper gastrointestinal bleeding, histamine H2-blockers reduced the number of
      operation. Proton pump inhibitors (PPI) were as effective as H2-blockers, or more
      effective than H2-blockers. Intragastric pH was raised to over 6 and was
      maintained in high level with the therapies using intravenous PPI injection. Oral
      administration of PPI also raised gastric pH to over 6 on the next day of the
      treatment, and then succeeded to treat bleeding. More effective and reliable
      therapies using PPIs are needed for rapid raising of intragastric pH and
      maintaining it in high level to treat upper gastrointestinal bleeding.

PMID- 9780709
TI  - [Recent surgical treatment of hemorrhagic diseases in the gastrointestinal
      tracts].
AB  - With an advent of conservative therapy for hemorrhagic gastroenterological
      diseases, the candidates for surgical treatment have been tremendously decreased.
      As to the treatment of ruptured esophagogastric varices, endoscopic injection
      sclerotherapy, endoscopic variceal ligation, TIPS have been practiced as a
      procedure of choice. Although these conservative treatments are effective and
      less invasive, the high incidence of rebleeding has been reported in the
      literature. Therefore the optimal choice is still controversial. It includes
      esophageal transection, selective distal splenorenal shunt. They should be
      considered as candidates for surgery if tests suggested that the patient could
      tolerate for surgical stress. On the other hand liver transplantation is
      considered to be an important therapeutic option in the United State for the
      patients with severe liver cirrhosis. Another recent advances in this field are
      laparoscopically assisted surgery. When bleeding is caused by divericulum or
      tumor of the gastrointestinal tracts, laparoscopic approach is another method of
      choice before laparotomy.

PMID- 9780710
TI  - [Nutritional therapy].
AB  - This article describes nutritional therapy for hemorrhagic gastro-intestinal
      diseases. The aim of this therapy is to protect and to accelerate cure of
      hemorrhagic lesion with rapid recovery of general condition. The accurate
      judgement for fluid therapy and contents, volume and timing of dietetic therapy
      is very difficult. However, it should always be considered, that excellent
      nutritional therapy influences prognosis of hemorrhagic digestive diseases to a
      great degree for its medication.

PMID- 9780711
TI  - [Risk factors for gastrointestinal bleeding].
AB  - Gastrointestinal bleeding sometimes causes life-threatening state. It is
      important to understand the underlining risk factors for prevention and treatment
      of this condition. In 1997, 81 patients with massive gastrointestinal bleeding
      were admitted to the life-saving center in Kyoto First Red Cross Hospital. In
      these patients, 14 subjects (17%) had been receiving hemodialysis. Eight patients
      (10%) were taking anti-coagulant or antiplatelet drugs. Eight patients (10%) had
      hypertension and were given calcium antagonists. Seven subjects (9%) had liver
      cirrhosis and/or hepatocellular carcinoma. Because these patients often fall into
      life-threating state, we must pay special attention to the prevention and cure
      for gastrointestinal bleeding. For example, it may be necessary to change to
      heparin free hemodialysis for patients having active bleeding. In anticoagulated
      patients, it may be required that sufficient hemostatic therapy without risking
      thromboembolic sequelae. In addition to careful managements, we have better to
      consider the eradication therapy for all of these high risk groups with
      Helicobacter pylori infection.

PMID- 9780712
TI  - [Gastrointestinal bleeding (introduction)].
AB  - Gastrointestinal (GI) bleeding is a common and important problem for all
      clinicians. Patients may present with signs of bleeding, such as hematemesis,
      melena, or hematochezia. The patient must first be hemodynamically stabilized.
      Initial assessment of patients with GI bleeding includes thorough history taking
      and physical examination. Patients with acute bleeding or an unstable condition
      must be resuscitated immediately and the source of bleeding must be localized to
      the upper or lower GI tract. Panendoscopy is often the initial diagnostic test
      and is useful to stop GI bleeding, at the same time.

PMID- 9780713
TI  - [Epidemiology of gastrointestinal hemorrhage].
AB  - We mentioned about epidemiology of gastrointestinal hemorrhage according to the
      clinical statistics. Most of recent reports has been investigated by emergency
      endoscopic examinations. Upper gastrointestinal hemorrhage was the most frequent
      and its clinical severity was severer than that of lower gastrointestinal
      hemorrhage. Hemorrhage from small intestine was rare, however they were mostly
      severe hemorrhage. Peptic ulcer was the most frequent disease as the upper
      gastrointestinal hemorrhage. Inflammation of colon was the most in the lower
      gastrointestinal hemorrhage. However, the varied diseases were recognized as
      origin of small intestinal hemorrhage, non epithelial tumor and inflammation were
      important.

PMID- 9780714
TI  - [Diagnosis and treatment of bleeding esophago-gastric varices].
AB  - Endoscopic injection sclerotherapy and/or endoscopic variceal ligation are well
      accepted and established in the treatment of bleeding esophageal varices.
      Endoscopic treatment for bleeding gastric varices is behind in hemostatic rate by
      5% ethanolamine oleate as sclerosant. However, since cyanoacrylate is employed as
      endoscopic injection sclerosant, hemostatic rate was greatly improved especially
      for the bleeding large gastric varices. In addition angiographic sclerotherapy
      (balloon occluded retrograde transvenous obliteration) is highly effective for
      large gastric fundal varices and no rebleeding is expected when successfully
      done. Endoscopic and angiographic sclerotherapy made great improvement in the
      treatment of esophagogastric varices.

PMID- 9780715
TI  - [Mallory-Weiss syndrome].
AB  - Mallory-Weiss syndrome is one of the cause of upper gastrointestinal hemorrhage,
      which an abrupt rise in abdominal pressure due to nausea or vomiting induces a
      tear near the esophagogastric mucosal junction. Mallory-Weiss syndrome represents
      about 3-15% of all cases of upper gastrointestinal hemorrhage. Mallory-Weiss tear
      is mainly located on the cardia part of the stomach side and spanning across the
      esophagogastric mucosal junction, only in esophageal side is rarely seen.
      Hemorrhage frequently ceases spontaneously. When endoscopic findings reveal
      persistent hemorrhage, endoscopic hemostatic technique using heater probe
      thermocoagulation or hemoclipping is necessary. After endoscopic hemostasis,
      fasting and inhibitors of acid secretion (H2-receptor antagonists or proton pump
      inhibitors) are recommended.

PMID- 9780716
TI  - [Acute gastroduodenal mucosal lesion].
AB  - AGML (acute gastric mucosal lesion) is now recognized as one of the important
      causal disease for gastrointestinal bleeding. If patients have sudden onsets of
      epigastralgia, epigastric discomfort, vomiting, hematemesis and melena following
      probable causes, it seems quite reasonable to make diagnosis of AGML by endoscopy
      with findings of gastric erosion, hemorrhagic gastritis and gastric ulcer. There
      are a variety of causes for AGML such as psychological and physical stress, drugs
      (NSAIDs, antibiotics, adrenal corticoid steroid, anti cancer drug), alcohol,
      serious organ failure of liver, kidney, heart, anisakiasis and etc. There are
      aslso a variety of endoscopic findings of AGML such as redness, edema, erosion,
      ulcer, bleeding which vary quickly in a short time. In this article we describe
      the definition, the cause, the clinical course, the location, the diagnosis, the
      endoscopic findings, our cases, the treatment of AGML.

PMID- 9780717
TI  - [Bleeding in chronic refractory peptic ulcer].
AB  - The authors reviewed the clinical problems of the bleeding in refractory ulcers.
      Incidence of refractory and easily-relapsing ulcers are about 40% of all chronic
      ulcers and their bleeding rate seemed to be more than 10% of them. We discussed
      the relationship between bleeding and risk factors such as age, NSAID use, H.
      pylori infection, etc. The consideration to them is very important in the present
      time, being difficult to predict ulcer bleeding.

PMID- 9780718
TI  - [Inflammatory bowel disease--Crohn's disease].
AB  - Acute massive hemorrhage from CD occurred in 3.0% in our institution. Forty CD
      patients with massive hemorrhage were reported in last 20 years in Japan. The
      ratio of male to female was 7.0. Ninety percent of them complicated the small
      intestinal CD. Massive bleeding was seen mostly in the ileum (82.5%) and next was
      in the colon (12.5%). However massive gastrointestinal hemorrhage is not often
      complicated in Crohn's disease, acute massive hemorrhage is occasionally
      critical. Therefore it is considered that CD should be treated carefully.

PMID- 9780720
TI  - [Bleeding from the alimentary tract--acute hemorrhage from gastrointestinal
      tumors].
AB  - The sources of bleeding from the alimentary tract varies significantly. In this
      article we describe clinical aspects of gastrointestinal tumors that cause
      gastrointestinal hemorrhage. Emergency operation for bleeding was decreased
      because of the advances in endoscopic treatment. However tumors with bleeding had
      the risk of rebleeding. When the diagnosis of tumor was established, resection
      was immediately recommended. Emergency operation was associated with a higher
      mortality rate than elective surgery. It was better to get histological diagnosis
      before surgery even in emergency operation. Local resection was chosen for the
      treatment of benign tumors and complete resection and lymph node dissection were
      chosen for most malignant tumors. It is important to build up a closer connection
      with endoscopists, surgeons and pathologists.

PMID- 9780719
TI  - [Ulcerative colitis and intestinal bleeding].
AB  - Ulcerative colitis is a nonspecific inflammatory disease of large intestine. Its
      inflammation is limited to intestinal mucosa. The most essential symptom is
      hematochezia, bloody stool and intestinal bleeding. Differential diagnosis among
      diseases having intestinal bleeding is clinically important. These diseases
      include Crohn disease, ischemic colitis, intestinal Behcet disease,
      Enterohemorrhagic E. coli including O157, antibiotics associated hemorrhagic
      colitis and so on. Drugs for the treatment of ulcerative colitis are
      sulphapyridine, 5-aminosalicylic acid, prednisolone, betamethasone and
      immunosuppressive drugs. Recently, leukocytapheresis and massive immunoglobulin
      7S treatment are available for the treatment of ulcerative colitis.

PMID- 9780721
TI  - [Ischemic disease of the intestine].
AB  - With the remarkable progress in diagnostic techniques, the recent increase in the
      incidence of arteriosclerosis and the gradually aging population, a great deal of
      attention is now being focused on intestinal ischemia and this disease has come
      to be regarded as one of the clinically important pathological conditions. From
      the clinic aspect, special attention should be directed to the artery which is
      involved in intestinal ischemia. Furthermore acute superior mesenteric arterial
      ischemia (SMA ischemia), ischemic colitis, non-occlusive mesenteric ischemia
      (NOMI) require serious attentions. Few specific findings of these pathological
      conditions can be obtained in general examinations, therefore angiography is the
      most useful technique for making difinitive diagnoses. SMA ischemia and NOMI are
      progressive diseases and their prognoses are poor. The progress of ischemic
      colitis is gradual and the conservative therapy consisting of fasting, drip
      infusion and antibiotic administration is generally effective in treating this
      disease.

PMID- 9780722
TI  - [Portal hypertensive gastropathy and colopathy].
AB  - Gastrointestinal bleeding in patients with portal hypertension is usually
      secondary to esophageal varices, but massive bleeding from gastric mucosal
      lesions and colonic mucosal lesions including colorectal varices, have been
      variably described. These lesions are called portal hypertensive gastropathy and
      colopathy. The incidence and profile of portal hypertensive gastropathy (PHG) has
      been frequently reported during the last decade, and many studies showed that
      development of PHG is influenced by coexisting esophageal varices, absence of
      major portal systemic shunts, severity of liver disease and sclerotherapy and is
      directly correlated with portal venous pressure. Although hyperdynamic congestion
      seems to be the underlying mechanisms for the development of PHG, results of
      gastric mucosal blood flow in patients with PHG is controversial. The treatment
      can be currently recommended to prevent bleeding, is oral administration of
      propranolol which decreased portal venous pressure. The clinical feature and
      profile of portal hypertensive colopathy is classified two groups, which are
      named colorectal varices and colonic mucosal lesions including vascular spider,
      dilated fine branching vessels. Although colorectal varices are usually seen at
      rectum and sigmoid colon, colonic mucosal lesions are seen all part of colon.
      Significant relationship between colorectal varices and liver disease has been
      reported and colorectal varices is highly appeared in patients with extrahepatic
      portal obstruction. Such patients are revealed arteriovenous communications at
      angiogram. In general, colonic resection or transanal ligation should be the
      first option for treatment of bleeding colonic varices and colonic mucosal
      lesions. Transendoscopic sclerotherapy may be an alternate choice.

PMID- 9780723
TI  - [Bleeding infectious enteritis].
AB  - A recent trend on bleeding intestinal infections in Japan was described.
      Salmonella Enteritidis infection occupied over 42% of food-borne diseases in
      1996. Salmonella Enteritidis is the most popular infectious agent for food-borne
      outbreak in Japan. Salmonella Typhimurium DT104 which is widely spread in Europe
      and in U.S.A. is not common in Japan. We experienced large outbreak of foodbore
      EHEC/VTEC O157: H7 infections in 1996. Since then, diagnostic and therapeutic
      studies on EHEC/VTEC infection and haemolytic uremic syndrome are promoted by the
      Government. HACCP may take an important roll for the prevention of large
      outbreaks of foodbore EHEC/VTEC infections.

PMID- 9780724
TI  - [Drug-associated hemorrhagic enteritis].
AB  - Drug-associated hemorrhagic colitis are divided into antibiotic associated
      hemorrhagic colitis (AAHC) and other drug associated hemorrhagic colitis. AAHC
      are mainly caused by oral usage of Ampicillin and its derivatives (85%).
      Initially AAHC are believed to be caused by Klebsiella oxytoca overgrowth.
      However, these organisum has no exotoxin like Clostridium difficile and
      pathogenesis of AAHC are still unresolved. Typical AAHC are diagnosed by
      colonoscopy with diffuse hemorrhage and edema mainly found in descending colon
      and transverse colon. NSAIDs are also the cause of hemorrhagic colitis like AAHC.
      Mephenamic acid are famous for this complication. Diarrhea is one of the main
      complication of oral 5-fluorouracil administration and even causes hemorrhagic
      colitis. Its histology are characteristic in gland atrophy. Gold colitis are
      reported 36 cases in rheumatoid arthritis patients. Exact mechanism of bleeding
      are not understood. NSAIDs may cause collagenous colitis and or lymphocytic
      colitis in RA patients. Other rare hemorrhagic colitis are associated with
      azathioprine, methyl dopa, interferon alfa etc. NSAIDs and anticoagulants are
      well known drugs for complication of GI bleeding making hemorrhagic enteritis.

PMID- 9780726
TI  - [Gastric haemorrhagic mucosal lesion in uremic patients].
AB  - It is well known that uremic patients frequently exhibit hemorrhagic lesions of
      the digestive tract and the recent introduction and progression of the
      hemodialysis treatment has changed the frequency of occurrence of a variety of
      gastrointestinal diseases. We have paid much attention on the upper digestive
      tract lesions of patients undergoing hemodialysis for chronic renal failure and
      have found that these lesions are predominantly mucosal hemorrhage of the stomach
      and gastroduodenal ulcers are rare. We have investigated the mechanism of onset
      of gastric hemorrhagic mucosal lesions focusing on blood flow, oxygen supply and
      infection of Helicobacter pylori. We conclude that not the blood flow but oxygen
      supply seems to play an important role and oxygen radicals produced at
      hemodialysis also may participate in the pathogenesis of mucosal hemorrhage. On
      the other hand, Helicobacter pylori does not seem to be important, because its
      infection rate is low among the patients investigated.

PMID- 9780725
TI  - [Gastrointestinal lesions in liver cirrhosis].
AB  - The gastrointestinal bleeding commonly observed in patients with liver cirrhosis
      is usually from esophageal and gastric varices, gastroduodenal ulcer, and
      congestive gastropathy. Portal hypertension is the major causative factor of
      pathogenesis of GI lesions. In the present review, we focus in gastric mucosal
      defense and Helicobacter pylori infection in liver cirrhosis. Gastric mucosal
      defense is reduced in liver cirrhosis, especially prostaglandins which play a
      role in the gastric mucosal defense decreased in the gastric mucosal of patients
      with liver cirrhosis and rat portal hypertension model. Although H. pylori is
      strongly associated with peptic ulcer disease and chronic gastritis, several
      studies showed no relationship between H. pylori infection and gastroduodenal
      ulcer or the infection and congestive gastropathy in liver cirrhosis. Reduced
      gastric mucosal defense may account for the pathogenesis of GI lesions in liver
      cirrhosis.

PMID- 9780727
TI  - [Stress ulceration related bleeding (SURB) in intensive care unit].
AB  - Today in critically ill patients the frequency of major stress ulceration related
      bleeding (SURB) has decreased. However this syndrome has not totally disappeared
      and its mortality remains very high once it develops. It's high mortality seems
      to be due to the facts that pathogenesis of SURB is mucosal ischemia resulting
      from splanchnic hypoperfusion in the setting of various insults in the ICU and
      that SURB reflects gut failure as a part of multiple organ failure (MOF).
      Therefore in the prevention of SURB, the optimization of tissue oxygen metabolism
      in splanchnic area must be considered in addition to the common prophylactic
      measures such as decreasing or neutralizing gastric acid and protecting gut
      mucosa.

PMID- 9780728
TI  - [Abdominal aneurysm].
AB  - Ulcer bleeding in the upper gastrointestinal tract is one of severe complications
      in the patients with abdominal aortic aneurysm (AAA). Retrospective analysis of
      patients with AAA and prospective endoscopic study revealed ulcer lesions
      occurred more frequently in AAA patients than in controls. Decreased gastric
      mucosal blood flow (GMBF) and accompanied consumption coagulopathy (CC) mainly
      contribute to the development of postoperative ulcer bleeding. Recently, the
      number of AAA patients with ulcer bleeding has been decreased remarkably after we
      started the anti-ulcer therapy for AAA patients with low GMBF or/and the
      administration of heparin for the patients with CC.

PMID- 9780729
TI  - [Complicated gastrointestinal bleeding of neoplastic diseases of the
      hematopoietic system].
AB  - The incidence of gastrointestinal bleeding has been reported as 10-30% of the
      patients with neoplastic diseases of the hematopoietic organ. The pathogenesis of
      gastrointestinal bleeding is multifactorial; direct leukemic cell infiltrations
      mucosal changes ensuing from bone marrow suppression or immunodeficiency states,
      infections due to various organisms, and preceding peptic ulcers. Once the
      diagnosis of hematopoietic neoplasm has been established, complete
      gastrointestinal work-up by endoscopy, CT-scanning or MRI should be mandatory.
      Early examination of the gastrointestinal tract has advantages of recognition of
      preceding peptic ulcers and their treatment, as well as providing prophylactic
      steps to the gastrointestinal mucosa vulnerable to hemorrhage. The prognosis of
      gastrointestinal bleeding complicated with hematopoietic malignancies seems to be
      poor due to the fact that DIC, multiorgan failures or fatal infections are
      seriously involved in their terminal stages.

PMID- 9780730
TI  - [Collagen diseases and gastrointestinal bleeding].
AB  - The main lesion of the collagen diseases involves blood-connective tissue, so
      every collagen disease is a accompanied by gastrointestinal bleeding to some
      degrees. The concept of systemic vasculitis had been confused, but recently, the
      criteria for each disease has been established. In addition to these vasculitis,
      antiphospholipid syndrome, amyloidosis, NSAIDs, steroid and secondary infection
      caused by the use of immunosuppressant are the candidates for the cause of
      gastrointestinal bleeding in the collagen diseases. In this paper, we described
      concisely about the gastrointestinal bleeding in SLE, RA, and systemic
      vasculitis.

PMID- 9780731
TI  - [Mutations in the genes of the HNF-family cause maturity-onset diabetes of the
      young (MODY)].
AB  - Maturity-onset diabetes of the young (MODY) is a monogenic form of non-insulin
      dependent diabetes mellitus (NIDDM) characterized by an early age of onset, often
      in childhood or adolescence and usually < 25 years of age, and autosomal dominant
      inheritance. Clinical characterization of patients with MODY indicates that
      impaired insulin secretion is the primary defect responsible for the
      hyperglycemia in these patients. Genetic studies have thus far identified five
      MODY susceptibility genes, four of which encode transcription factors; HNF
      (hepatocyte nuclear factor)-1 alpha, HNF-1 beta, HNF-4 alpha, and IPF1. The
      association of mutations in the genes for these transcription factors with early
      onset familial diabetes indicates the importance of the HNF-regulatory network in
      determining pancreatic beta-cell function.

PMID- 9780732
TI  - [Guanylin family: new intestinal peptides regulating salt and water homeostasis].
AB  - Guanylin and uroguanylin are novel peptides that are first isolated from rat
      jejunum and opossum urine, respectively. They bind to and activate guanylyl
      cyclase-C (GC-C) to regulate intestinal and renal fluid and electrolyte transport
      through the second messenger, cyclic GMP. Heat-stable enterotoxins produced by
      pathogenic bacteria have close structural similarities to guanylin and
      uroguanylin, and they use this mimicry to act on GC-C, causing life-threatening
      secretory diarrhea. Guanylin primarily is restricted to the intestine, whereas
      uroguanylin is present in the stomach kidney, lung and pancreas in addition to
      intestine. Guanylin and uroguanylin in the intestine are secreted into the lumen
      and blood in response to sodium chloride administration. These peptides will
      function in salt and water transport in the intestine and kidney by luminocrine
      and/or endocrine actions. Guanylin peptide family links the intestine with the
      kidney and could play the physiological roles in the control of water and
      electrolyte balance.

PMID- 9780733
TI  - [Pathogenesis of acute coronary syndromes].
AB  - Coronary artery diseases may categorized into asymptomatic disease, angina
      pectoris, myocardial infarction, chronic heart failure, and sudden coronary
      death. Unstable angina, acute myocardial infarction, and sudden cardiac death are
      known as the acute coronary syndromes. Coronary atheroma is unstable in the
      patients with acute coronary syndromes. Stable plaques will be unstable when
      dynamic alterations occur. The alterations are plaque rupture, plaque hemorrhage,
      coronary thrombosis and vasospasm. They act each other. We analysed the
      histopathology of coronary arteries who died of acute myocardial infarction in 85
      cases. It showed that the risk factors of plaque rupture are clusters of form
      cells, eccentric plaque with soft lipid rich core, and thinning of fibrous cap in
      atheroma. Most of these cases ruptured at edge of the atheroma.

PMID- 9780734
TI  - [Recent classification of the genus Streptococcus].

PMID- 9780735
TI  - [The application of a transponson, Tn4351, to an oral anaerobe, Porphyromonas
      gingivalis].

PMID- 9780736
TI  - [RAPD typing of Campylobacter jejuni and comparison with Lior's or Penner's
      serotyping system].
AB  - Campylobacter jejuni were isolated from 7 epidemic outbreaks (121 isolates), 15
      patients with gastroenteritis, chicken meats (47 isolates) and chicken cecal
      contents (70 isolates). The isolates and one standard strain of C. jejuni JCM2013
      were analysed by randomly amplified polymorphic DNA method (RAPD). Total of 254
      C. jejuni isolates were divided 68 different RAPD types which included strains
      that did not to divided by Lior's or Penner's serotyping system. To compare the
      similarities of RAPD patterns among the isolates, the amplification patterns of
      DNA were estimated by means of the Dice coefficient, and clustering of strains
      was based on the unweighted average pair group method (UPGMA) to facilitate the
      plotting of a dendrogram. It suggests that amplification band patterns of human
      isolates were different from those of chicken ones. Thus additional information
      given from RAPD profiles serves for epidemiological investigation and RAPD
      analysis is recommended as rapid and effective typing method.

PMID- 9780737
TI  - [Women and Science-Helena Rubinstein Awards for Women in Science].

PMID- 9780738
TI  - [Responsibility of the lateral geniculate nucleus in photosensitive epilepsy:
      dipole tracing method].
AB  - We studied the location of the electric generator of photoparoxysmal discharges
      using a scalp-skull-brain dipole tracing (DT) method. By this method, the
      location of epileptic discharges on each scalp EEG was calculated as an
      equivalent current dipole (ECD) in 8 cases of epilepsy who had photoparoxysmal
      discharges. We divided these cases into groups A and B (4 cases each), comprising
      of patients with and without visually-induced seizures, respectively. The ECDs of
      the 3 cases in group A corresponded to the small area adjacent to the lateral
      geniculate nucleus on MRI superimposed. On the other hand, the ECDs of all cases
      in group B located at the corpus callosum. This study suggests the pathways of
      epileptic discharges from the epileptic focus are different between two groups.
      It is supposed that neural activity of the lateral geniculate nucleus might be
      responsible for the generator mechanism of photoparoxysmal discharges which
      evokes photosensitive epilepsy.

PMID- 9780739
TI  - [Brainstem edema in patients with acute encephalopathy and encephalitis].
AB  - The author reported eleven patients with brainstem edema on cranial CT. Nine had
      acute encephalopathy or Reye syndrome and the other two had acute encephalitis.
      Seven cases died and four cases survived. Dead cases showed brainstem edema
      significantly faster than the survivors. Laboratory examinations revealed
      significant differences of LDH, platelet and HCO3(-) between the two groups. Six
      patients died in the winter. The duration of convulsion was more than 30 minutes
      in all the dead cases.

PMID- 9780740
TI  - [Auditory brainstem responses (ABR) in patients with Wolfram syndrome].
AB  - Auditory brainstem responses (ABR) and other evoked potentials were studied in
      four patients with the Wolfram syndrome. In three cases ABR was abnormal in the
      early stage of the disease. There was no responses or only the wave V with
      prolonged latency at a stimulation level of 80 dBnHL. A prolongation of the I-V
      interpeak latency (IPL) was also revealed at a stimulation level of 105 dBnHL.
      The remaining patient showed shortening of the I-V IPL. The visual evoked
      potentials showed prolonged peak latency in three cases, and the median nerve
      short latency somatosensory evoked potentials were normal in two cases. These ABR
      findings indicated not only sensory neuronal hearing loss but also a degenerative
      change in the brain stem in the Wolfram syndrome.

PMID- 9780742
TI  - [A case of acute necrotizing encephalopathy of childhood with a good outcome].
AB  - We experienced a case of acute necrotizing encephalopathy of childhood with a
      good outcome. The disease continued for about three weeks, and the patient
      recovered with a sequela of mild left-hemiparesis. On the brain magnetic
      resonance imaging, abnormal intensity areas in the thalamus and putamen reduced
      size at an early stage of the disease. After 1 year, his mental and motor
      development seemed to be almost normal, but brain single photon emission computed
      tomography and electroencephalography were abnormal. Subclinical functional
      abnormalities persisted longer than had been expected.

PMID- 9780741
TI  - [Manifestation of Chiari II symptoms following peritoneal shunt tube extension].
AB  - A 5-year-old boy with hydrocephalus and a lumbar myelomeningocele underwent
      extension of peritoneal tube of ventriculoperitoneal (VP) shunt system. Prior to
      the operation he had been able to walk independently with the use of braces, to
      speak complex sentences and to sing songs. After the surgery, he lost
      consciousness and became critically ill with irregular respiration. He was
      artificially ventilated for 10 days, and then recovered, with sequelae of right
      facial paresis and slight dysarthria. T1 weighted magnetic resonance image showed
      high intensities of the medial part of the inferior lobe of the cerebellum and
      medulla oblongata, which were interpreted as representing edema. This case
      illustrates that Chiari II malformation can become symptomatic after a VP shunt
      trouble.

PMID- 9780743
TI  - [MRI, SPECT and MRS findings in a case of acute hemiplegia syndrome with a marked
      hemispheric brain edema].
AB  - Magnetic resonance imaging (MRI), single photon emission computed tomography
      (SPECT) and magnetic resonance spectroscopy (MRS) were successively recorded in a
      3-year-old girl with the acute hemiplegia syndrome. She was admitted to our
      hospital with complaints of fever, loss of consciousness and right side dominant
      clonic convulsions evolving into status epilepticus, and then recovered with
      sequelae of aphasia and right hemiparesis. Electroencephalography showed a
      generalized slow rhythm at the onset, and very low activities on the left
      hemisphere in the follow-up records. Brain CT and MRI revealed edema of the left
      hemisphere initially, followed by left side dominant brain atrophy. No cerebral
      vascular lesion was detected by magnetic resonance angiography. N-Isopropyl
      [123I]-iodoamphetamine SPECT showed marked hypoperfusion of the left hemisphere
      accompanied by crossed cerebellar diaschisis. MRS at the initial stage detected
      decreased N-acetyl-aspartic acid and increased lactic acid signals in the
      bilateral hemisphere, which subsequently normalized only on the right side. These
      findings suggested brain damage and neural cell death in the left cerebral
      hemisphere, caused by acute encephalopathy. SPECT and MRS are useful new
      techniques to study the pathophysiology of the acute hemiplegia syndrome.

PMID- 9780744
TI  - [A case of congenital toxoplasmosis confirmed by detection of Toxoplasma gondii
      in placenta].
AB  - We report a case of congenital toxoplasmosis with a prenatal diagnosis of fetal
      hydrocephalus. A CT scan performed at birth revealed ventricular dilation with
      calcification. The serum and CSF Toxoplasma specific IgM were elevated. The
      diagnosis was confirmed by the presence of Toxoplasma cysts in the placenta, and
      detection of the Toxoplasma SAG1 gene by a polymerase chain reaction (PCR)
      (placenta, positive; CSF, negative). Signs of active central nervous system
      infection, such as the decreased CSF glucose, and elevated CSF protein, neuron
      specific enolase and LDH, resolved after initiation of treatment with
      pyrimethamine and sulfazoxine. A PCR test using the placental tissue may be
      useful for the rapid diagnosis of congenital toxoplasmosis.

PMID- 9780745
TI  - [A case of non-photosensitive, self-induced epileptic seizures with pacygyria].
AB  - We report an 11-year-old boy with a non-photosensitive epileptic self-induced
      seizures, pacygyria and familial ataxia. His grandmother and aunts had
      dysarthria, and his mother had developed progressive ataxia and myoclonus since
      40 years old. His older sister had ataxia, mental retardation and epilepsy. As
      for the boy, motor developmental delay with muscle hypertonicity of left
      extremities was recognized at the age of 5 months. Mental retardation and ataxia
      was recognized at the age of 3 years and slight mental regression is recognized
      at the age of 11 years. No special findings were detected in an examination of
      his blood and cerebrospinal fluid, including amino acids, lysosomal enzymes
      activity and genetic analysis for dentatorubralpallidoluysian atrophy. Brain
      magnetic resonance imaging revealed pachygyria of the right cerebral cortecies.
      At the age of two, he began to induce seizures with impairment of consciousness
      in himself by waving his right hand over his face which was directed toward a
      source of bright light. At the age of seven, he developed spontaneous seizures
      with impairment of consciousness. An EEG showed frequent spikes in the occipital
      areas, on the right and left sides occurring either independently or
      synchronously. Intermittent photic stimulation and pattern stimulation did not
      induce a paroxysmal discharge in EEG. Ictal EEG suggested that the origin of the
      seizures was the occipital lobe. Treatment with valporate and zonisamide was
      effective in reducing the seizures. The findings of our case imply the
      pathogenesis of self-induced seizures and the relationship between PME and
      neuronal migration disorders.

PMID- 9780746
TI  - [A case of acute polyradiculoneuritis with multiple cranial nerve palsy and
      cerebral lesion--possible evidence of encephalo-myelo-radiculo-neuropathy].
AB  - We report a case of acute polyradiculoneuritis with multiple cranial nerve palsy
      and cerebral lesions. A boy, born on July 26, 1987, developed unusual sensation
      on the extremities, backache and sleep disturbance on June 23, 1996. On July 2,
      following a complaint of blindness he developed a convulsion and was admitted to
      our hospital. Neurological examination revealed intact consciousness, severe
      external ophthalmoplegia, bifacial palsy and generalized areflexia. On the next
      day, flaccid tetraplegia and respiratory dysfunction developed and progressed
      without disturbance of consciousness. After tracheal intubation he was under
      mechanical ventilation. A lumbar puncture examination showed clear CSF with
      increased protein 166 mg/dl. no cells and normal myelin basic protein. Serum
      antibodies against gangliosides (GM1, asialo-GM1, GD1b and GQ1b) were not
      detected. A posterior tibial nerve conduction velocity was mildly delayed with
      disappearance of F- wave. On the other hand, very slow background activity was
      shown by EEG, extensive focal hypoperfusion of cerebral blood flow by SPECT and
      supratentorial multiple high intensity lesions by T2 weighted MRI of the brain.
      There were no abnormal signals in the brainstem and cerebellum on MRI. His
      condition dramatically improved after plasmapheresis. The abnormal findings of
      SPECT and MRI promptly disappeared within 3 weeks, although abnormal signs on EEG
      persisted. He was successfully weaned off the respirator and recovered strength
      of the limbs. He was discharged on August 28, 1996, with supported walk and
      bifacial palsy, then he completely recovered by 7 months. The condition of case
      was compatible with 'encephalo-myelo-radiculo-neuropathy', a disease entity that
      had previously been reported in a few patients in whom with Guillain-Barre or
      Fisher syndrome and cerebral symptoms co-existed.

PMID- 9780747
TI  - [Update on the role of diet in recurrent nephrolithiasis].
AB  - The role of nutritional factors in the pathogenesis of recidivating
      nephrolithiasis is reviewed. The ingestion of liquid calcium and citrates is
      inversely associated with the risk of developing stones, while the ingestion of
      proteins, sodium, uric, and oxalates have a direct relationship. One should not
      restrict the ingestion of calcium in the diet, but rather one should recommended
      a normal or high ingestion of some 850 mg/day, and rather, one should restrict
      the ingestion of proteins, oxalate, and sodium, as well as keeping up a diuresis
      greater than 1500 cc/day.

PMID- 9780748
TI  - [Body mass index and the desire of weight loss in a group of young women].
AB  - With the aim of obtaining information as to whether the desire to lose weight
      responds to criteria of health, or whether this is only a question of esthetics,
      the relation between the body mass index (BMI) as an indicator of obesity, and
      some attitudes with respect to weight, were analyzed in a group of 254 apparently
      healthy women between the ages of 14 and 55 with a variety of occupations
      (students, housewives, and women working outside the home), using a questionnaire
      designed for the study. An analysis was also made of the types of methods used
      for the voluntary loss of weight, as well as other aspects of slimming. The
      sample was classified into three groups according to the BMI: low weight (BMI <
      20 kg/m2), adequate weight (BMI = 20-25 kg/m2), and overweight (BMI > 25 kg/m2).
      Of the total number of women studied, only 42% were satisfied with their weight.
      Of those with a low weight, 35% manifested discontent, and of these, 69% wanted
      to lose weight and only 19% had attempted to increase it. Among the women with
      and adequate BMI, 71% indicated not being content with their weight, with 95%
      wishing to reduce it. In the group of overweight women only 13% were satisfied
      and all the rest expressed a desire for losing weight. The size and volume of the
      thighs (28%), hips (22%), buttocks (20%), and abdomen (19%) were the areas
      producing the greatest amount of discontent. The most common methods for losing
      weight were: no snacking between meals (54%), physical exercise (53%), and low
      calorie diets (33%). Only 19% went to see a specialist. The use of laxatives
      (1.5%) and other slimming products (3.5%) was minimal.

PMID- 9780749
TI  - [Parenteral nutrition of patients under intensive chemotherapy: comparative study
      of two lipid emulsions].
AB  - Neoplastic patients receiving intensive chemotherapy often need total parenteral
      nutrition (TPN), with lipid emulsions based on long-chain triglycerides (LCT) or
      medium-chain triglycerides (MCT). Potential benefits of MCT include easier
      metabolism and limited storage. Our present investigation was performed to define
      if there is any real clinical advantage of any of these lipid emulsions in this
      group of patients. Fifty-one patients receiving the LCT emulsion and sixty of
      them receiving the MCT-LCT one were evaluated retrospectively. TPN with 40% of
      non-protein kilocalories as fat was administered during a mean time of 11.5 days.
      No differences in total cholesterol, albumin, prealbumin, transferrin, bilirubin,
      alkaline phosphatase, gamma-glutamyl transpeptidase and transaminases were found
      between both groups, neither in nitrogen balances. In conclusion, in a group of
      neoplastic patients receiving intensive chemotherapy, we did not found any
      advantage of TPN with LCT or MCT-LCT either in nutritional laboratory parameters
      or in liver function.

PMID- 9780750
TI  - [Growth hormone and its effects on cholesterol and lipoprotein metabolism
      following surgical intervention (hGH and cholesterol metabolism during surgery)].
AB  - The objective of this work was to determine whether the increase in serum GH,
      IGF1, glucose and insulin levels caused by the administration of hGH modifies the
      normal response of cholesterol and lipoproteins to surgical aggression. A
      prospective, randomized, and double blind study is carried out in 28 patients
      operated for gallstones and diverticulitis. The control group (n = 15) was not
      given anything except conventional fluidtherapy in the postoperative period: the
      patients in the hGH (n = 13) group were also given 8 IU of hGH during the first
      five days after the intervention. The comparative study of the triglycerides,
      cholesterol, LDLc, HDL-c, and A-1 B apolipoproteins shows that in the group
      treated with hGH the normal response of cholesterol and lipoproteins to surgical
      aggression is attenuated.

PMID- 9780751
TI  - [Relationship between the number of daily meals and the energy and nutrient
      intake in the elderly. Effect on various cardiovascular risk factors].
AB  - The metabolic consequences of the consumption of a diet depend, in part, on the
      frequency and distribution of meals. The aim of the present study was to examine
      the number of meals taken per day by elderly persons, and to analyse the
      relationship between the number of meals per day on the intake of energy and
      nutrients, the incidence of obesity/overweight, and different cardiovascular risk
      factors. Food intake was monitored for five consecutive days using 'precise
      individual weighing' for institutionalised subjects (n = 58), and by means of a
      'food intake record' for independent subjects (n = 92). The number of meals taken
      per day was recorded, along with anthropometric data, blood pressure and serum
      lipid and lipoprotein levels. No subject took only one meal per day, 7.3% took
      two, 56.7% took three, 33.3% took four and 2.7% took five. Only 10% of subjects
      took a mid-morning meal. Breakfast and merienda (a light evening snack) were the
      meals most frequently omitted. A positive, significant relationship was found to
      exist between the number of meals taken per day and the intake of fibre (r =
      0.2737), thiamin (r = 0.1671), pyridoxine (r = 0.2060), magnesium (r = 0.2423)
      and the percentage of energy provided by carbohydrates (r = 0.2144). Women
      subjects who took 2-3 meals per day showed greater body mass indices and a
      greater proportion were overweight/obese compared to those who took 4-5 meals per
      day. Subjects who took 4-5 meals per day showed higher levels of HDL-cholesterol
      and lower levels of LDL-cholesterol/HDL-cholesterol and cholesterol/HDL
      cholesterol than did those who took fewer meals per day. Inverse, significant
      relationships were also found between the number of meals per day and serum
      cholesterol (r = 0.2297) and LDL-cholesterol levels (r = 0.1984). Taking into
      account energy and nutrient intakes, the incidence of obesity/overweight and
      serum lipid and lipoprotein levels, the consumption of 4-5 meals per day would
      seem more advisable for the elderly than the taking of fewer meals.

PMID- 9780752
TI  - [Current model of breakfast for different age groups: children, a adolescents and
      adults].
AB  - The objective of the present work is to assess the current breakfast model in
      different age groups: children between the ages of 6 and 12 years (n = 54);
      adolescents between the ages of 13 and 17 years (n = 174); and adults, older than
      18 years of age (n = 252). For this a questionnaire has been designed that
      follows the standards of that used for a similar study by our team in 1984 on a
      sample of 1350 individuals. The modified and amplified questionnaire included
      open and closed questions about: the omission of breakfast and its causes, foods
      that are a part of breakfast, the most frequent types and the variations, the
      role of the second breakfast, the number of fasting hours since dinner, the time
      spent of breakfast, and the subjective opinion regarding the importance or not of
      having breakfast. 98.95% answer yes to the question do you have breakfast, but
      only 9% eats a nutritionally correct breakfast, one defined as that breakfast
      that supplies 20% of the total energy and includes foods from at least four
      different groups. All the children included some form of milk product in their
      breakfast. The adolescents consumed the lowest proportion of cereals (19.4%) and
      the highest proportion of pastries (24.2%). The percentage of adults who drink
      coffee with milk (57%) and sugar (37.7%) is significantly higher than that it the
      other two groups. Bread (37.7%), pastries (28.3%) and cookies (26.1%) are the
      solid foods eaten most by the adults. The children spend the longest time on
      breakfast. 35.9% of the sample varies their breakfast, 43.1% never does, and 21%
      does so sometimes. The average time elapsed between dinner and breakfast is 10.5
      +/- 1.2 hours. It is advisable to have a more nutritionally balanced breakfast,
      including different foods from at least four groups, and including a greater
      variety in the menus.

PMID- 9780753
TI  - [Parenteral nutrition in oncologic patients].
AB  - The aim of this work is to carry out a follow-up of oncological inpatients who
      received parenteral nutrition (PN). We analysed the connection between the
      clinical situations and the indication and type of PN administered. A
      retrospective review of oncological patients who received PN during 1996 was
      carried out. Age, sex, primary tumor, PN indication and compliance degree,
      nutritional evolution, different categories of nutritional intervention,
      characteristics of PN as well as related complications and connected with PN were
      analysed. 33 patients, 23 female and 10 male, between 20 and 82 years old, were
      studied. 39% received PN with intensive antineoplastic therapy; 55% received PN
      as supportive treatment in various clinical situations related to the tumor or
      with antineoplastic therapy; 6% received palliative PN. 25 patients received PN
      without lipids and 8 total PN. The mean duration of PN was 10 days. 17 patients
      received PN by peripheric venous route and 16 through central venous catheter.
      The PN was well tolerated. In conclusion, most patients (94%) complied with some
      of the criteria established for the PN indication. The biggest percentage of
      patients in treatment with PN were divided into two main groups: patients with
      intensive antineoplastic therapy and patients with gastrointestinal disfunction
      caused by tumor or antineoplastic therapy. The role of PN in oncological patients
      it is not defined yet. The incidence of complications due to PN was low and
      without clinical relevance.

PMID- 9780754
TI  - [Extracellular polysaccharides of coagulase-negative staphylococci and their role
      in pathogenicity].
AB  - Coagulase-negative staphylococci have been recognised as important pathogens in
      biomaterial-associated infections and a number of studies have been carried out
      to identify virulence factors for these microorganisms. Among them bacterial
      slime has been most extensively investigated, since it is considered to
      participate in the staphylococcal adherence and growth on polymer surfaces. It
      has been shown that on the surface of infected biomaterial bacteria are embedded
      in a heavy slime layer, that allows them to escape host defence and resist to the
      antimicrobial action of antibiotics. In this review article the reasons for the
      growing pathogenicity of coagulase-negative staphylococci are discussed. Also the
      methods for studying bacterial adherence and slime production are presented and
      the latest data on chemical composition of coagulase-negative extracellular
      polysaccharides are reported.

PMID- 9780755
TI  - [The role of cytokines in the pathology of acute myeloid leukemia].
AB  - An overview of literature data concerning the role of some cytokines in growth
      regulation of acute myeloid leukemia cells is presented. Clinical application of
      cytokines in anti-leukemia therapy is also discussed.

PMID- 9780756
TI  - [Lipoprotein lipase (LPL) in the pathogenesis of atherosclerosis].
AB  - The role of lipoprotein lipase (LPL) in the development of atheromatosis is
      subject of the increased interest for about 20 years, since then Zilversmit
      observed that LPL activity is found in greater amounts in atherosclerotic than
      normal arteries. The general action of this enzyme is hydrolysis of triglycerides
      in triglyceride rich lipoproteins and thus regulation of metabolism of
      circulating as well antiatherogenic as proatherogenic lipoproteins. The effect of
      LPL on the biology of arterial wall seems to be atherogenic. The mechanisms of
      this effect of LPL is 1) augmentation of the adhesion and aggregation of LDL; 2)
      influence on the oxygen modification of LDL and increased uptake of oxy-LDL by
      macrophages; 3) dysfunction of endothelial barrier and retention of atherogenic
      lipoproteins in the arterial wall and 4) the activity of LPL macrophage origin.
      Possible atherogenic actions of LPL based on in vitro experimental studies are
      reviewed.

PMID- 9780757
TI  - [Genetic basis of malignant melanoma].
AB  - Cytogenetic analysis has contributed significantly to defining genomic region
      frequently altered in malignant melanoma. In the case of 1p, 6q i 9p consistent
      losses or partial deletions have predicted the location of tumor suppressor
      genes. Recent evidence suggests that the p16 CDKN2 gene located at 9p21 is
      important in sporadic and familial melanoma pathogenesis.

PMID- 9780758
TI  - [Mastocyte proteinase].
AB  - Recent studies have led to a rapid expansion of knowledge concerning the
      structure and biology of mast cells neutral proteinases. Therefore, in this paper
      tryptases, chymases, carboxypeptidases and cathepsin G have been described and
      their biological roles have been discussed.

PMID- 9780759
TI  - [Antioxidative mechanisms in response to reactive forms of oxygen, apoptosis and
      differentiation of myogenic cells].
AB  - In this paper regard was put on contemporary matters related to apoptosis of
      myogenic cells of different types (myocardium, visceral, skeletal muscle) and
      updated theories on the action mechanisms of free radicals and their contribution
      to this process. Concern was put on the activity of certain growth factors and
      antioxidants belonging to group of polyphenols on the extent of apoptosis in
      myoblasts held in culture. Similarities between the pathways depicting the
      process of muscle differentiation and resistance to programmed cell death are
      presented. The concept of myogenic cell differentiation and implications to
      apoptosis induced by particular oxidants is extensively discussed.

PMID- 9780760
TI  - [Subarachnoid block in ambulatory surgery].

PMID- 9780762
TI  - [Bibliometric analysis of the original articles published in the Revista Espanola
      de Anesthesiologia y Renimacion in 10 years (1987-1996)].
AB  - OBJECTIVE: To describe the original research articles published in Revista
      Espanola De Anestesiologia y Reanimacion (REAR) from 1987 through 1996, as well
      as to characterize the citations included in those articles. MATERIAL AND
      METHODS: The 299 articles published as original research in REAR over the past 10
      years (1987 through 1996) were analyzed. The bibliographic aspects examined were
      coauthorship (authors/paper index), citations per article, isolation in function
      of language of publication of references, degree of obsolescence of articles
      based on year of references cited ("half-life"), self-citation and degree of
      dispersion of citations. RESULTS: The authors/paper index was 5.16 +/- 1.62. No
      statistically significant difference was found in number of authors over the 10
      year study period. Mean number of references cited per article was 24.05 +/-
      12.02. We found statistically significant differences for 1993 and the period
      1987 to 1988, and 1994 and the year 1987 (p < 0.001). The "half-life" of articles
      was 6 when analyzing on a year-by-year basis; this index ranged from 5.5 to 7,
      with no significant annual differences. REAR articles accounted for 4.02% of all
      citations. English was the most frequent language of cited publications, with
      6,240 references (86.8%), followed by Spanish with 621 (8.64%), French with 223
      (3.1%) and German with 74 (1.03%). Of the 7,191 references analyzed, 6,447
      (89.65%) were of scientific journals. Books are the second most commonly cited
      type of document, with 623 (8.66%) citations. Analyzing journals cited 25 or more
      times, we found that 74.19% of the articles (4,783/6,447) had been published in
      5.3% of the journals (36/678). Seven journals of anesthesia, which represented
      1.03% of all journals (7/678) appeared in 52.81% of references of this type
      (3,405/6,447). CONCLUSIONS: The number of authors of original research articles
      published in REAR in the last 10 years was high. Spanish authors in
      anesthesiology cite mainly literature in English; use up-to-date sources of
      information, mainly journals; and take a large proportion of information from a
      small number of journals, which are those of greatest international impact in our
      specialty.

PMID- 9780761
TI  - [Intradural anesthesia with a 27-gauge Sprotte needle for arthroscopic knee
      surgery in ambulatory patients under 40 years of age].
AB  - OBJECTIVE: To assess the clinical usefulness of intradural anesthesia through a
      27 gauge Sprotte ("pencil point") needle for arthroscopic knee surgery in
      outpatients under 40 years of age. PATIENTS AND METHOD: A retrospective study of
      116 patients under 40 scheduled for arthroscopic knee surgery, analyzing the
      incidence of post-dural puncture headache and backache after anesthesia provided
      with a 27 gauge (0.4 mm) Sprotte needle. Follow-up assessments were performed 24,
      48 and 72 hours after surgery. We also studied technical difficulty and failure
      rate encountered in achieving blockade with this type of needle. RESULTS: We
      recorded one case of headache (0.86%) that resolved within 48 hours with
      conservative treatment. Backache was reported by eight patients (6.8%) and was
      described as slight in all cases. The small caliber and design of the spinal
      needle caused no technical difficulties and anesthesia was successfully provided
      for all patients. Time of hospital stay ranged from 330 to 420 minutes (mean 360
      +/- 45 minutes). No patient had to stay overnight. CONCLUSIONS: The results
      confirm that intradural anesthesia with 27 gauge Sprotte needles is an acceptable
      anesthetic technique for outpatient surgery in young patients given that the rate
      of complications is low.

PMID- 9780763
TI  - [Effect of a 3-in-1 block in arthroscopic knee surgery. Comparative study with
      subarachnoid block].
AB  - HYPOTHESIS AND OBJECTIVES: Trunk blockades in arthroscopic knee surgery are
      rarely performed because combined blockade of the sciatic and lumbar plexus
      nerves are required, particularly if ischemia is required. We aimed to assess the
      efficacy of the "3-in-1 block" combined with intraarticular infiltration of local
      anesthetic for arthroscopic meniscectomy. The results were compared with our
      standard technique, subarachnoid anesthesia. PATIENTS AND METHODS: Forty ASA I-II
      patients undergoing arthroscopic meniscectomy without ischemia. The patients were
      randomly assigned to receive "3-in-1 block" with 40 mL of 1.5% mepivacaine (T
      group, n = 20), or the standard technique of subarachnoid puncture with 3 mL of
      2% lidocaine (S group, n = 20). Twenty minutes after puncture patients in both
      groups received intraarticular injections of 20 ml of bupivacaine 0.25% with
      1:200,000 adrenaline in the knee. Surgery began 10 minutes later. We assessed
      requirements for sedation during surgery, degree of satisfaction during surgery
      according to the surgeon and the patient, hemodynamic variables at predetermined
      times, postoperative pain (on a verbal scale and related to consumption of
      analgesics in the first 48 hours after surgery), and the appearance of side
      effects attributable to anesthetic technique. RESULTS: Demographic variables were
      comparable in the two groups and no surgical events were recorded. Eighteen
      patients in the T group and one in the S group required sedation during surgery
      (p < 0.05). Blood pressure was significantly lower in the S group than in the T
      group (p < 0.05). No patient in the T group required atropine and/or ephedrine
      during surgery, whereas 5 patients in the S group did (p < 0.05). Postoperative
      evolution was similar in the two groups. No postoperative complications
      attributable to the techniques were recorded. CONCLUSIONS: The "3-in-1 block"
      combined with joint infiltration of local anesthetics may be an effective
      alternative when subarachnoid anesthesia is contraindicated in patients
      undergoing arthroscopic meniscectomy.

PMID- 9780765
TI  - [Resuscitation of the burned child in critical condition].
AB  - Recent advances in surgical techniques, control of infection and nutritional
      support have dramatically increased the survival rates of burned children. The
      characteristics of severely burned pediatric patients dictate that management be
      different from that required for adults in the intensive care unit. The formulas
      for fluid replacement should be based on body surface rather than weight in
      children and adjusted for degree of stress and age, with appropriate monitoring
      and treatment of hypothermia, pain and associated psychological disorders. Early
      assessment and treatment of airway obstruction and gas and smoke inhalation
      syndromes with high FiO2 is necessary; prophylactic endotracheal intubation may
      be required.

PMID- 9780764
TI  - [Comparison of the effect of desflurane with isoflurane in patients over 65 years
      of age: multicenter study].
AB  - OBJECTIVE: To compare the effects of desflurane (DES) and isoflurane (ISO) in
      patients over 65 years of age based on recovery, hemodynamic variables, need for
      additional drugs and postoperative rates of nausea and vomiting. PATIENTS AND
      METHODS: Ninety-eight patients were anesthetized with DES (n = 51) at an inspired
      concentration of 3% or ISO (n = 47) at a concentration of 0.5%, both combined
      with 60% nitrous oxide. Anesthetic concentration was later adjusted to maintain
      hemodynamic variables within 20% above or below baseline. Analgesia was provided
      with fentanyl and neuromuscular relaxation with atracurium. After surgery,
      anesthetic gases were withdrawn. We then recorded variables related to anesthetic
      recovery, postoperative analgesia and the rates of nausea and vomiting. RESULTS:
      Mean time (+/- SD) until eye opening was 7.6 +/- 5.5 minutes for patients
      anesthetized with DES and was significantly less than the 14.4 +/- 8.9 minutes
      taken by patients anesthetized with ISO (p < 0.01). Patients anesthetized with
      DES spent 23 minutes less time in the recovery room than did patients
      anesthetized with ISO (p < 0.05). There were no significant differences in need
      for fentanyl, atracurium, postoperative analgesia, hemodynamic variables or rates
      of nausea or vomiting. CONCLUSIONS: Patients over 65 years of age anesthetized
      with DES recovered in half the time of patients anesthetized with ISO. DES is a
      safe anesthetic for elderly patients and may offer clinical advantages.

PMID- 9780766
TI  - [Epidural hematoma after removal of an epidural catheter].
AB  - Epidural hematoma is a rare but serious neurological complication of epidural
      anesthesia. We report the case of a 61-year-old man with squamous cell carcinoma
      of the lung who suffered an epidural hematoma after undergoing right double
      lobectomy. Before anesthetic induction an epidural catheter was inserted to the
      D5-D6 space for postoperative analgesia. Surgery was without noteworthy events
      and the patient was extubated in the operating room; 5,000 IU of low molecular
      weight heparin was injected subcutaneously every 24 hours and 5 mg of methadone
      was provided by epidural catheter every 8 hours. After removal of the catheter
      three days after surgery, lumbar back pain and hypoesthesia, and weakness in both
      legs appeared. Epidural hematoma was suspected and treatment with 30 mg.kg-1 of
      methylprednisolone i.v. was started. Nuclear magnetic resonance imaging of the
      lumbar spine confirmed the presence of a hematoma at D6-D8. Neurologic symptoms
      improved in the following hours and additional surgery was not required. The
      patient was released without neurological symptoms 10 days after lung surgery. We
      discuss the prevalence, etiology and treatment of epidural hematoma related to
      epidural anesthesia.

PMID- 9780767
TI  - [Silent pulmonary aspiration of barium after esophagogastroduodenography and
      subtotal gastrectomy].
AB  - We describe a 66-year-old patient who underwent subtotal gastrectomy and
      omentectomy for gastric adenocarcinoma six days after esophago-gastro
      duodenography with barium contrast medium. In the postoperative period a series
      of chest films showed bronchogram due to aspiration of the contrast medium from
      the stomach, and finally multiple cottony infiltrates bilaterally. The patient
      had no respiratory symptoms and 6 days after admission to the intensive care
      recovery unit, he was moved to the general surgery ward for observation. Follow
      up later passed to the outpatient with satisfactory evolution. We conclude that
      pulmonary aspiration occurred after extubation in the operating theater, since
      during the operation the patient remained stable hemodynamically and
      respiratorily. This case corroborates the theory of the existence of silent
      aspiration without pulmonary complications and the need to adjust clinical
      treatment, which can be conservative when, once the process is diagnosed, no
      symptoms present.

PMID- 9780769
TI  - [Malignant hyperthermia: clinical classification as a diagnostic test. Apropos of
      2 cases].

PMID- 9780768
TI  - [Brugada syndrome and anesthesia. Apropos of a case].
AB  - We describe a patient with a tentative diagnosis of Brugada syndrome who was
      given general anesthesia without complications. We review the main
      characteristics of Brugada syndrome.

PMID- 9780770
TI  - [Anesthesia of a patient with morbid obesity: anesthetic and logistic
      management].

PMID- 9780771
TI  - [Problems associated with the use of armored endotracheal tubes in children].

PMID- 9780772
TI  - [Comments on the management of anaphylactic shock caused by rupture of an
      unsuspected hepatic hydatid cyst].

PMID- 9780773
TI  - [The personality of the anesthesiologist].

PMID- 9780774
TI  - [The "Heart Area" of Juan Canalejo Hospital Complex. A new approach to clinical
      management].
AB  - The present work describes the process by which the pilot project of clinical
      management of the Hospital Complex Juan Canalejo, designated as "Heart Area", was
      implemented. In the first section, the needs and reasons that led to the
      undertaking of this project are explained. The project's objectives and operative
      strategies are listed. In the Material and Methods section, three basic aspects
      of the "Heart Area" are described: selection criteria of the "Area", its
      structure and function, and its foundation and development. In the Results
      section, we compare the activity undertaken in the "Area" to the situation
      present prior to its implementation, in relation to quality and costs. Finally,
      in the Conclusions, we comment on the important implications that our project can
      have within the Hospital Complex Juan Canalejo as well as in the health care
      field in general.

PMID- 9780775
TI  - [The Institute of Cardiovascular Diseases. The redesigning project of
      Cardiological and Surgical Services of the Hospital Clinic of Barcelona].
AB  - Changes in health systems are determining new hospital organization forms. The
      patient focused hospital suppose a new radical design of hospital processes from
      the patient's viewpoint. This paper defines the re-engineering process of the
      Cardiology and Cardiovascular Surgery Services of the Hospital Clinic of
      Barcelona in order to develop and Institute. The change consists fundamentally in
      a reorganization of the direction organs, creating a staff commission and
      director. The chief nursing and chief management report to the director. Also, a
      patients admission and management unit, that manage the beds infrastructure of
      both services has been developed. The first year results show a reduction of the
      length of stay and an increase in the in-hospital and external activity.

PMID- 9780776
TI  - [New management systems of cardiovascular clinical units].

PMID- 9780777
TI  - [Cellular and molecular bases of cholesterol accumulation in the vascular wall
      and its contribution to the progression of atherosclerotic lesion].
AB  - The rupture of atherosclerotic plaques depends mainly on their composition.
      Vulnerable plaques are those that contain a large lipidic core, which derives
      either from the retention and modification of LDL and/or from necrosis of foam
      cells. Most foam cells derive from monocyte/macrophages. Although some of them,
      especially in advanced plaques, derive from smooth muscle cells. Different
      receptors involved in the process of foam cell formation have been identified:
      e.g., scavenger receptors, VLDL receptors and alpha 2-macroglobulin/low density
      lipoprotein receptor-related proteins. The LDL derived cholesterol collected by
      these receptors is transformed through the enzyme acyl CoA cholesterol acyl
      transferase (ACAT) in esterified cholesterol, the hallmark of foam cell
      formation. High density lipoprotein (HDL) allows the release of free cholesterol
      from the plasmatic membrane inducing the regression of atherosclerotic lesions.

PMID- 9780778
TI  - [Effect of the location of myocardial infarction on the variability of heart
      rate: a study during the acute phase].
AB  - OBJECTIVES: The influence of the location of acute myocardial infarction on the
      autonomic tone and its evolution during the first hours post-infarct has not been
      fully evaluated. The aim of this study was to analyze this effect using a
      spectral analysis of the heart rate variability. PATIENTS AND METHODS: Forty-nine
      consecutive patients with acute myocardial infarction (22 anterior and 27
      inferior) in sinus rhythm and free of diseases and drugs which could affect heart
      rate variability were studied. Five-minute Holter recordings within each hour
      between 10 and 33 hours after the onset of symptoms were analyzed, calculating
      the standard deviation of NN intervals and the spectral power of the high and low
      frequency bands using normalized units. RESULTS: The standard deviation was
      higher in inferior infarcts (51.4 +/- 23.4 ms vs. 38.6 +/- 14.8 ms in anterior
      location; p < 0.05) and gradually decreased over time in both locations. The
      relative distribution of high- and low-frequency bands did not show significant
      differences related to the infarct location. An inverse significant correlation
      between the high-frequency component and time was observed for anterior infarcts
      (r = -0.98; p < 0.001) as well as in the inferior group (r = -0.75; p = 0.04).
      Conversely, the low-frequency power gradually increased in anterior infarcts (r =
      0.98, p < 0.001) while remaining stable in inferior locations (r = -0.08; NS).
      CONCLUSIONS: A gradual reduction of heart rate variability was observed in
      patients with acute myocardial infarction during the time of monitorization. The
      spectral analysis suggests that anterior infarcts present a progressive increase
      of sympathetic activity and a reduction of vagal tone, whereas inferior infarcts
      show a parallel reduction in both components of the autonomous nervous system.

PMID- 9780779
TI  - [Diagnostic efficacy of myocardial tomographic imaging in the detection of
      restenosis after coronary angioplasty].
AB  - INTRODUCTION AND OBJECTIVES: To analyze the efficacy of single photon emission
      tomography (SPET) with 99mTc-compounds for the diagnosis of restenosis of
      previous percutaneous transluminal coronary angioplasty (PTCA). PATIENTS AND
      METHODS: Seventy-one patients (16 women, median age: 60 years, 35 with
      multivessel disease, 78 arteries with PTCA) with previous PTCA and with coronary
      angiography performed after scintigraphy were studied. 99mTc-SPET exercise (53
      with MIBI and 18 with tetrofosmin) was performed, for clinical reasons, to all
      patients between one month and 4 years after PTCA. Intravenous dipyridamole was
      administered simultaneously to 16 patients who had insufficient exercise.
      RESULTS: SPET sensitivity, specificity, positive predictive values, negative
      predictive values and global values were all significantly higher than those
      obtained with exercise tests (80% vs 63%; p = 0.05; 83% vs 37%; p = 0.001; 91% vs
      69%; p = 0.007; 64% vs 31%; p = 0.009, and 81% vs 55%; p = 0.0006, respectively).
      These results were significantly superior in patients with one vessel disease
      than in patients with multivessel disease. CONCLUSIONS: SPET exercise with 99mTc
      compounds is a test with a high efficacy for the diagnosis of post-PTCA
      restenosis, mainly in patients with one vessel disease.

PMID- 9780780
TI  - [A simplified method of continuous-wave Doppler noninvasive assessment of
      ventricular relaxation in mitral insufficiency].
AB  - INTRODUCTION AND OBJECTIVES: The minimum value of dP/dT is a parameter of
      diastolic function that can be estimated noninvasively by analyzing the profile
      of velocity of the mitral regurgitant jet, recorded by continuous-wave Doppler.
      This estimation requires a complex analysis of the curves that impedes its
      practical use. Our objective was to validate a simplified method to estimate
      noninvasively the value of dP/dTmin when mitral regurgitation exists. We
      calculated the pendient of the profile of velocity of the curve of mitral
      regurgitation during its deceleration, between 3 and 1.5 m/s, an interval that
      defines a difference in pressure using the formula delta p = (4v2(1) - 4v2(2)).
      We divided this interval by the time needed by the jet to decelerate from 3 to
      1.5 m/s, obtaining the rate of pressure decay, in mmHg/s. METHODS: We provoked
      mitral regurgitation in five pigs and registered dP/dT and the curve velocity of
      mitral regurgitation simultaneously, by micromanometer-tipped catheter and
      continuous-wave Doppler, respectively. The rate of pressure decay was calculated
      on the mitral regurgitation curve. RESULTS: We obtained 29 simultaneous
      registers. The coefficient for the correlationship between dP/dT and the rate of
      pressure decay was with an r value of 0.62 (p < 0.0001). The rate of pressure
      decay underestimated systematically the value of dP/dT. Intra and interobserver
      variability of TDP was 9 and 11%, respectively. CONCLUSIONS: This study validates
      a simplified method to estimate dP/dT noninvasively, with acceptable correlation
      with invasive measurements and adequate reproducibility.

PMID- 9780781
TI  - [Heart pathology of extracardiac origin. XI. Cardiac repercussions of diabetes
      mellitus].
AB  - Diabetes mellitus is one of the diseases with the greatest risk of developing
      coronary disease (CD), with the estimation of this risk in relation to the
      general population being from 2 to 4-fold greater. The existence of diabetes
      worsens the prognosis of CD and thus, postinfarction mortality in these patients
      is double that observed in non-diabetic patients. Together with the risk factors
      found in the general population, those of special interest are those derived from
      diabetes itself, such as hyperglycemia, dyslipemia, coagulation disorders and
      hyperinsulinemia or insulin resistance. Among these, the most important is
      probably the hyperglycemia which may contribute to the appearance of CD by
      different mechanisms such as proteic glycosylation, accumulation of sorbitol,
      increase in the synthesis of protein kinase C or oxidative stress. It must not be
      forgotten that an old controversy has recently been brought up suggesting that
      sulphonylureas may have a certain cardiotoxic effect, probably acting on the
      potassium channels dependent on ATP. Acute myocardial infarction in diabetic
      patients carries a greater risk of congestive heart failure, recurrent
      infarction, arrhythmia and cardiogenic shock, with one of its characteristics
      being the possibility of being silent when autonomic neuropathy is present. The
      prognosis of CD may be markedly improved by obtaining optimum glycemic control
      during the hours following infarction using intensified treatment. Diabetic
      myocardiopathy as a differentiated nosology responsible for alterations in
      myocardial contractile function and greater prevalence of heart failure in these
      patients seems to be clearly demonstrated although its etiology remains unknown.

PMID- 9780782
TI  - [Agenesis of the left coronary trunk. A case report and bibliographic review].
AB  - Clinical and angiographic features are described in a fifty-five years old man,
      with long-standing clinical manifestations of ischemic heart disease. In addition
      to severe coronary atherosclerosis, congenital atresia of the left main coronary
      was present. A description of the coronary anomaly found and a discussion of its
      meaning and significance are presented.

PMID- 9780783
TI  - [Myxoma of the left ventricle: a cause of syncope in an adolescent].
AB  - Clinical diagnosis of cardiac tumours is often difficult. We present the case of
      a 17 year-old boy in whom a left ventricular tumour was discovered during on
      diagnostic work-up for a syncope. The tumour was removed and histology confirmed
      the diagnosis of myxoma.

PMID- 9780784
TI  - [Acute myocarditis caused by varicella virus].
AB  - We describe a case of acute myocarditis subsequent to varicella virus infection.
      We comment on the rarity of the clinical entity together with the nonspecificity
      of the routine diagnostic technique (EKG, X-ray, echocardiography study, routine
      laboratory, etc.) linked with the excellent gain of antibodies cardiac
      gammagraphy joined with viral serology, after the primary suspicion factor prior
      to the presence of skin lesions, fever and thoracic pain.

PMID- 9780786
TI  - [Surgical treatment of hypertrophic myocardiopathy using a video-assisted
      technique. Apropos of a case].
AB  - The use of endoscopic technology is gaining more and more popularity within
      cardiac surgery. We present a case employing endoscopic instruments in the
      resection of the interventricular septum in a patient with hypertrophic
      cardiomyopathy unresponsive to medical treatment. Advantages of this technique
      are discussed.

PMID- 9780785
TI  - [Mobile thrombus in the right cardiac cavities in patients with severe pulmonary
      thromboembolism. Importance of echocardiography].
AB  - The pulmonary thromboembolism is a frequent and severe disease, usually difficult
      to recognize, specially in patients with thrombotic material trapped within right
      heart cavities. We present our experience in three patients with severe pulmonary
      thromboembolism where echocardiographic study demonstrated the presence of huge
      mobile thrombus in right heart cavities, which demanded urgent therapy with
      excellent results. We would like to stress that echocardiographic study in these
      patients could be elective diagnostic procedure, avoiding the realization of
      pulmonary arteriography, which could bring risk of possible thrombus
      mobilization.

PMID- 9780787
TI  - Vertical ring gastroplasty (VRG) in the treatment of the serious clinical
      obesity. Results and complications.
AB  - OBJECTIVE: The morbid obesity is a serious polysystematic disease to which it is
      necessary to offer a surgical solution when the conservative alternatives fail.
      METHODS: In a period of five years, 50 patients with vertical ring gastroplasty
      (VRG) have been evaluated and protocolized in the program of surgery of the
      morbid obesity, with an average weight of 134.3 kg corresponding to an overweight
      and body mass index (BMI) average respectively, of 69.7 kg and 49.8 kg/m2.
      RESULTS: The early morbidity has been scarce and the postoperative average stay
      of 7 days. The decrease of the percentage of weight, overweight and BMI was
      maximum 2 years later, with losses of 52 kg, with a percentage of loss of average
      overweight of 76.8% and a fall of 21 points in the BMI; however there was a
      partial recovery of the indexes in the following years. The accompanying
      pathology was solved in the period of studied time, although 84% of the patients
      referred vomits and practically 100% dietary limitations. CONCLUSIONS: The
      gastroplasty is a quick, simple technique and of scare morbimortality, although
      it is being subjected to criticism for the restrictions in the diet, quality of
      life and disruptions of the line of clamped. However, nowadays there is not a
      consensus on the ideal bariatric solution, and as a surgical alternative, the
      vertical gastroplasty can represent one of the techniques of choice for certain
      selected types of serious obesity.

PMID- 9780788
TI  - Efficacy of alpha 2b versus lymphoblastoid interferon in treatment of chronic
      hepatitis C. A randomized trial.

PMID- 9780789
TI  - Clinical, histopathological, cytogenetic and prognostic differences between
      mucinous and nonmucinous colorectal adenocarcinomas.
AB  - OBJECTIVE: To assess the clinical and biological significance of histological
      typing of colorectal carcinomas. PATIENTS AND METHODS: The retrospective analysis
      of 142 consecutive patients who underwent surgical resection of a mucinous (MC; n
      = 27; 19%) or a nonmucinous (nMC; n = 115; 81%) colorectal adenocarcinoma was
      carried out. The two groups were compared in terms of the clinical features, p53
      gene expression (antiserum CM1), proliferating cell nuclear antigen (PCNA)
      labeling index, DNA ploidy (by flow cytometry), histopathological features,
      prognosis and recurrence rate. RESULTS: The two types of tumors differed with
      respect to patient age, location, morphology, pattern of genetic lesions and type
      of tumor recurrences. Twenty-five percent of the patients with MC and 9% of those
      with nMC (p = 0.04) were under 50 years of age. The incidences of right MC and
      left MC were similar, while the majority of the nMC were located on the left side
      (p = 0.04). The MC were of higher grade and their margins more infiltrative than
      those of the nMC (p = 0.001 and p = 0.01, respectively), p53 nuclear staining was
      observed less frequently in the MC than in the nMC (30% vs 55%; p = 0.03). The
      PCNA labeling index was higher in the nMC (46% vs 21%; p = 0.05). We observed no
      significant differences with respect to tumor stage, incidence of vascular
      invasion or prevalence of lymphocytic infiltration. The prognosis was similar in
      both groups, although their recurrence patterns differed, with a tendency toward
      locoregional recurrence in the cases of MC. CONCLUSION: These findings suggest
      that, despite their similar prognoses, these two types of lesions are
      epidemiologically, phenotypically and genotypically different and, thus, result
      from distinct carcinogenic pathways.

PMID- 9780790
TI  - A prospective trial of self-expanding metal coated stents in the palliation of
      malignant dysphagia.
AB  - OBJECTIVE: To analyze the use of self-expanding metal coated esophageal stents a
      palliative therapy of malignant dysphagia. METHOD: We performed a one year
      prospective study placing 12 stents in 10 patients with malignant dysphagia.
      RESULTS: The insertion mean time was lower than 25 min, and most of our patients
      (70%) reported a good tolerance. Dysphagia score improved immediately and it
      lasted until death with no occlusions. Complications appeared early, 17% at the
      time of placement, with one patient having a life-threatening complication. The
      probability for these patients not to develop any complications after the three
      first weeks will be about 60%. CONCLUSIONS: Self-expanding metal coated
      esophageal stents provide a fast and lasting relief in malignant dysphagia, with
      a good tolerance.

PMID- 9780791
TI  - [Hilar and peripheral cholangiocarcinomas].
AB  - Cholangiocarcinoma is the most frequent malignant neoplasm of the bile ducts. It
      continues to be a diagnostic and therapeutic challenge because of its form of
      growth and intimate relation with hepatic hilus structures. While
      cholangiocarcinomas situated distal to the biliary confluence have well-defined
      characteristics and treatment, cholangiocarcinomas situated in or proximal to the
      biliary confluence are problematic. A study was made of the so-called
      intrahepatic cholangiocarcinomas by establishing two types, peripheral and hilar.
      Their features and therapeutic options are analyzed and published results are
      reviewed.

PMID- 9780792
TI  - [Peritoneal tuberculosis: evaluation of the response to treatment by analysing
      the CA 125 levels].
AB  - A case of a 32 years old woman with fever and exudative ascites is described.
      Tuberculous peritonitis was confirmed by abdominal laparoscopy, peritoneal biopsy
      and Lowenstein culture. A serum CA 125 level was 861 U/ml before therapy. The CA
      125 level decreased a 30% after three weeks of antituberculous treatment. This
      tumor marker may be used to follow disease activity in tuberculous ascites.

PMID- 9780794
TI  - [Epithelioid gastric leiomyosarcoma (malignant leiomyoblastoma) with intense
      expression of smooth muscle desmin and actin].

PMID- 9780793
TI  - [Efficacy of an ultrashort protocol in the eradication of Helicobacter pylori].

PMID- 9780795
TI  - [Primary chylous ascites in cirrhotic patients: description of 2 new cases].

PMID- 9780796
TI  - [Non-hodgkin's lymphoma and cytomegalovirus gastric infection].

PMID- 9780797
TI  - [Reference values in esophageal manometric studies].

PMID- 9780798
TI  - Study of esophageal function by standard esophageal manometry in 72 healthy
      volunteers. Proposal for national reference values. Spanish Group for the Study
      of Digestive Motility.
AB  - AIM: A multicenter study was carried out to establish the normal values of
      different esophageal motility variables in a large group of healthy volunteers to
      be considered as national reference values. PARTICIPANTS: Standard esophageal
      manometry was performed in 72 healthy individuals (38 males/34 females) of a mean
      age of 43 years (range: 18-73 years). Equipment and methodology were standardized
      by the participating centers prior to initiation of the study. Lower and upper
      esophageal sphincter characteristics and the features of the esophageal motility
      waves were analyzed. RESULTS: The amplitude and length of the peristaltic waves
      of the esophageal body increased distally, while the speed of proximal
      progression was lower than that of the distal speed. The presence of a reduced,
      but significant number of double peaked simultaneous, spontaneous and non
      transmitted waves were of note. Upper and lower esophageal sphincter motility as
      well as relaxation capacity and pharyngeal contraction were defined. CONCLUSIONS:
      Given the characteristics of the population analyzed and the statistical
      consistence of the results obtained, the values herein reported may be considered
      as national reference values for esophageal motility studies carried out by
      standard esophageal manometry.

PMID- 9780799
TI  - Comparative effect of growth hormone and plerocercoid growth factor in the
      intestinal resection in rat.
AB  - OBJECTIVE: After massive bowel resection, absorption depends on how fast the
      mucosal adaptation takes place. This work aims at assessing the trophic effect of
      growth hormone (GH) and its analogue, the plerocercoid growth factor (PGF), on
      the intestinal mucosa after 90% small bowel resection. EXPERIMENTAL DESIGN: 24
      male Wistar rats were divided into four groups of 6: Control (laparotomy), 90%
      small bowel resection (RID), resection and treatment with GH during 14 days (RID
      + GH) and resection and PGF treatment (RID + PGF). Intestinal mucosal adaptation
      was assessed by measuring mucosal weight and height, and evaluating the
      regenerative activity by measuring proliferation cell nuclear antigen (PCNA)
      labelling index. RESULTS: Bowel resection itself caused a significant increment
      of jejunal and ileal mucosal height in comparison with the control group. GH and
      PGF did not change this increase. Jejunal and ileal proliferation indexes were
      significantly higher than those in controls and they were significantly higher in
      both RID + GH and RID + PGF groups. CONCLUSIONS: GH and PGF cause a proliferative
      effect on the intestinal mucosa, even in hyperproliferative states such as the
      small bowel resection. This finding might have a clinic application.

PMID- 9780800
TI  - Upper digestive tract dyspepsia and early gastric cancer.
AB  - AIM: The study of the frequency and evolution of upper digestive tract dyspepsia
      in a group of patients operated for early gastric cancer (EGC) and to perform a
      strategy of diagnosis for the patients with long term upper digestive tract
      dyspepsia. METHODS: Clinical data of 35 patients operated for EGC were
      retrospectively evaluated. The frequency, characteristics and evolution time of
      upper digestive tract dyspepsia, main when it began more than 6 months before
      surgery, were analyzed. Radiologic and endoscopic exams carried out for diagnosis
      were also evaluated. Histological diagnosis of surgical specimens were
      considered, looking for the presence of chronic atrophic gastritis, intestinal
      metaplasia, and peptic gastric ulcer. RESULTS: Long-term upper digestive tract
      dyspepsia was present in 27 patients (mean evolution time of 43.4 months).
      Clinical changes of previous symptoms that suggested gastric carcinoma were not
      found in 15 patients. Concurrent peptic gastric carcinoma were not found in 15
      patients. Concurrent peptic gastric ulcer along with EGC was diagnosed by
      histology in 11 patients, and chronic atrophic gastritis and intestinal
      metaplasia were both present in the non-tumoral gastric mucosa in all cases.
      CONCLUSIONS: 1) Unspecific upper digestive tract dyspepsia is frequently found in
      patients with EGC. 2) Endoscopy should be the first exam performed in patients
      with upper digestive tract dyspepsia. 3) The patients with gastric ulcer, chronic
      atrophic gastritis or intestinal metaplasia must be submitted to sequential
      endoscopic follow-up.

PMID- 9780801
TI  - Analysis of the quality of life in patients after pelvic pouch operation.
AB  - AIM: The aim of this study is to analyse the quality of life in patients with
      ileoanal pouch respect to a diverting loop ileostomy. MATERIALS AND METHODS:
      Fifteen patients (8 women and 7 men) with mean average age of 33 years who
      underwent mucosal proctectomy, colectomy, ileal-pouch-anal anastomosis and
      temporary loop ileostomy. Quality of life was studied when the patients had an
      ileostomy and follow-up evaluation, one year after restitution of anal
      defecation. The surgeons' evaluation was done using a health scale. RESULTS:
      Among the patients with temporary ileostomy, 40% reported bad tolerance, 53%
      leakage of stoma bag and 26% skin problems. The mean stool frequency among
      ileoanal anastomosis was four per day, 87% reported total continence, 13% had
      major complications and they needed pouch removal. 67% patients with ileostomy
      reported dietary restrictions against 13% patients functioning with pelvic pouch
      (p = 0.004). 13% patients with ileostomy had restricted sport activities. Social
      activities were restricted for 40% and 26% had limitations in their ability to
      work. Sex life was affected in 20% of patients with ileostomy and 13% of patients
      with ileal pouch anastomosis. 73% of patients presented an excellent level of
      satisfaction with pouch. CONCLUSION: Quality of life after ileoanal pouch
      anastomosis is higher than ileostomy.

PMID- 9780802
TI  - [Gastroduodenal lesions and non-steroidal anti-inflammatory agents. What role
      does Helicobacter pylori play in this relationship?].
AB  - Helicobacter pylori infection and non-steroidal anti-inflammatory drugs (NSAIDs)
      are the two most important causal factors in gastroduodenal ulcer disease. The
      coincidence of both occurs frequently and, therefore, demonstration of a possible
      relationship, and the consequent attitude (giving or not eradication therapy)
      would have important implications. The lower H. pylori prevalence in gastric
      ulcer, in comparison with duodenal ulcer, seems to be due greatly to NSAIDs
      intake, although in a low number of patients this ulcer is not explained by
      either of these factors. Therefore, the finding of a gastroduodenal ulcer in an
      H. pylori-negative patient should suggest other possible causes, and among them
      NSAIDs outstands. Histologic gastritis found in a patient with NSAIDs intake is
      related to the subjacent presence of H. pylori and not with NSAIDs. It is not
      clear whether, in patients taking NSAIDs, the infection favors the appearance of
      dyspeptic symptoms. The possibility of H. pylori and NSAIDs having a synergistic
      effect on gastroduodenal ulcer disease is a debatable issue. H. pylori
      eradication in patients taking NSAIDs does not confer a clear advantage in ulcer
      healing, and the possible protecting effect of eradication on the development of
      an ulcer in subjects taking NSAIDs is doubtful. In an H. pylori-positive patient
      in whom an ulcer occurs while taking NSAIDs, it is not possible to know for sure
      whether the ulcer has been caused by the organism, by NSAIDs, or by both, and
      therefore it seems logical to administrate an eradication therapy. However, H.
      pylori eradication with the intention of preventing appearance of gastroduodenal
      lesions is not so evident. Finally, indications of traditional preventive
      treatment (with antisecretory drugs or mysoprostol) should not be influenced by
      the concomitant administration of H. pylori eradication therapy.

PMID- 9780803
TI  - [HELLP syndrome. Analysis of 2 cases].
AB  - HELLP syndrome (Hemolysis, Elevated Liver Enzymes, Low Platelets), one of the
      gestational diseases of the third trimester of pregnancy associated to eclampsia
      or preeclampsia, has a varied clinical expression, that include poor symptomatic
      patterns with malaise and/or dyspepsia, even several patterns with fatal outcome.
      We show two cases with clinical and laboratory criterion of HELLP syndrome, but
      with different clinical presentations. It's analyzed the pathogenicity, clinical
      pathological expression, course and therapeutics options in HELLP syndrome.

PMID- 9780804
TI  - [Aberrant pancreas in ileum as the cause of anemia].

PMID- 9780805
TI  - [Primary adenocarcinoma of the jejunum].

PMID- 9780806
TI  - [Survival after massive resection of the intestine in an 82-year-old male].

PMID- 9780807
TI  - [Dysphagia as an unusual onset form of Crohn's disease].

PMID- 9780808
TI  - Depression in survivor of stroke: a community-based study of prevalence, risk
      factors and consequences.
AB  - Depression in survivors of stroke is both common and clinically relevant. It is
      associated with excess suffering, handicap, suicidal ideation and mortality and
      it hampers rehabilitation. Most of the data currently available are derived from
      clinical studies. The objective of the present study was to study the prevalence,
      risk factors and consequences of depression in survivors of stroke, in a large (n
      = 3050) community-based study of older (55-85 years) people in three regions of
      the Netherlands. Depression was measured using the CES-D scale; histories of
      stroke were obtained using self-reports and data from general practitioners. The
      study was designed as a case-control study, using both bivariate and multivariate
      analyses. The prevalence of depression in stroke survivors was 27%, which was
      significantly higher than the base rate (OR 2.28, 95% CI 1.61-3.24). Both stroke
      related disease characteristics and psychosocial characteristics of the
      respondents were predictors of depression. The consequences of depression were
      most evident in the realm of disability and impairment of well-being. The
      patterns of service utilization showed that depressed survivors of stroke are
      relatively high users of a wide range of health services.

PMID- 9780809
TI  - Suicide in Greece 1980-1995: patterns and social factors.
AB  - A nationwide study of suicide in Greece from 1980 through 1995 demonstrated: 1. A
      mean age-standardized suicide rate of 5.86/100,000 for males and 1.89/100,000 for
      females. 2. An increase in suicide rates with age, especially in males. 3.
      Significant rising trends of male suicides in the 45-54 age group. 4. Significant
      declining trends of female suicides in age groups 15-24, 75-84, and total. 5. The
      lowest suicide rates among married men and women. 6. Exceptionally high rates in
      young widowed men. 7. Rural suicide rates were twice as high as urban rates. 8.
      Suicide methods were mostly violent, especially in males. 9. Hanging was the most
      common method, employed in approximately 50% of all suicides. The low suicide
      rates and the trends observed can probably be attributed to a synthesis of social
      and cultural characteristics of the Greek people and ongoing changes in Greek
      lifestyle.

PMID- 9780810
TI  - Parental rearing and problem behaviours in male delinquent adolescents versus
      controls in northern Russia.
AB  - The purpose of this study was to investigate possible relationships between
      parental rearing practices and problem behaviours in a sample of male delinquent
      adolescents versus controls. A total of 133 subjects from a juvenile correction
      centre and 108 matched school-children in the Arkhangelsk region, Russia, were
      assessed by means of the EMBU questionnaire and Youth Self-Report. Delinquents
      were more severely treated by parents and had more pronounced problem scores.
      Furthermore, problem scores were found to be highly correlated with parental
      rejection and lack of emotional warmth in both delinquents and controls. Parental
      rearing practices may influence the development of problem behaviours. The
      implications of these findings with regard to preventive measures are discussed.

PMID- 9780811
TI  - Postnatal depression and social supports in Vietnamese, Arabic and Anglo-Celtic
      mothers.
AB  - The significance of a western woman's social supports to postnatal depression is
      well documented. We examine which deficits in components of their social support
      network are associated with postnatal depression in women from a non-English
      speaking background. The social support network and postnatal mood of 105 Anglo
      Celtic, 113 Vietnamese and 98 Arabic women were assessed at 6 weeks postpartum.
      The role of social supports in determining scores on the Edinburgh Postnatal
      Depression Scale (EPDS) was analysed using multiple regressions. For Anglo-Celtic
      women, low postnatal mood was associated with perceived need for more emotional
      support from partners and mothers. For Vietnamese women, low postnatal mood was
      associated with poor quality of relationship with the partner and a perceived
      need for more practical help from him. For Arabic women, low postnatal mood was
      associated with perceived need for more emotional support from partners. We
      conclude that cultural factors mediate the relation between social supports and
      postnatal depression more likely to become clinically depressed (Lovestone and
      Kumar 1993) and infants may have adverse cognitive, behavioural and emotional
      outcomes, which can be linked to the postnatal depression (Murray and Cooper
      1996).

PMID- 9780812
TI  - Self-reported long-standing psychiatric illness as a predictor of premature all
      cause mortality and violent death: a 14-year follow-up study of native Swedes and
      foreign-born migrants.
AB  - The present study focuses on the associations between self-rated long-standing
      psychiatric illness, ethnicity, all-cause mortality and violent death (accidents
      and suicide), in a sample of 39,155 Swedish-born and foreign-born individuals.
      The study was designed as a longitudinal follow-up study, covering the period
      between 1 January 1979 and 31 December 1996. The data were analysed by a
      proportional hazard model and the results are given as hazard ratios (HR) with
      95% confidence intervals (CI). Self-reported long-standing psychiatric illness
      was a strong risk factor for total mortality: women had an HR of 2.13 (CI = 1.78
      2.54) and men an HR of 1.84 (CI = 1.53-2.21), when adjusted for background
      factors such as country of birth, civil status and socio-economic factors.
      Finnish men had an increased risk of all-cause mortality compared to Swedes in
      the final model, when adjusted for socio-economic factors. Long-standing
      psychiatric illness was also a strong risk factor for violent death, with an HR
      of 3.51 (CI = 2.32-5.32). The risk of violent death was 2.4 times higher for men
      than for women. The conclusions of the present study are that self-reported long
      standing psychiatric illness is a strong predictor of an increased all-cause
      mortality and increased mortality from violent death. The increased age-adjusted
      mortality risk for foreign-born men could be explained by disadvantaged social
      and economic conditions. Only Finnish men demonstrated an independent increased
      all-cause mortality risk.

PMID- 9780814
TI  - The Dubai Community Psychiatric Survey. IV. Life events, chronic difficulties and
      psychiatric morbidity.
AB  - The relationship between life events, chronic social difficulties and psychiatric
      morbidity was investigated in 297 women selected at random as part of the Dubai
      Community Psychiatric Survey. The PSE-ID-CATEGO system was used to identify
      psychiatric cases, based on an Index of Definition level of 5 or more. Life
      events in the 6-month period prior to illness or interview were elicited through
      the Life Events and Difficulties Schedule. Chronic difficulties were explored
      through direct questioning based on a list of possible problems. The study
      demonstrates a significant excess of marked and moderately threatening life
      events in acute cases of psychiatric disorder (50%) compared to chronic cases
      (16.7%) and non-cases (27.9%). The association was particularly marked for events
      in the 3-month period before the onset. Around 33% of psychiatric morbidity may
      be attributed to marked and moderately threatening life events. Rates for mild
      events were similar in the three groups of subjects. Subjects experiencing
      chronic social difficulties included a significantly higher proportion of cases
      (33.3%) than those who did not experience such difficulties (9.1%). The effect of
      chronic social difficulties was more pronounced than, and independent of, the
      effects of life events. There were no interactions between life events and
      vulnerability factors in their effect on psychiatric morbidity, although numbers
      were small. The results suggest that the overall influence of life events and
      chronic difficulties on psychiatric morbidity is commensurate with that in
      Western societies, despite the different coping traditions of Islam.

PMID- 9780813
TI  - Does a hostel's managing agency determine the access to psychiatric services of
      its residents?
AB  - This study examines the effect of managing agency (local authority, private or
      voluntary) on the use of other health and social care services by residents in
      mental health hostels and group homes with different levels of staffing in
      England and Wales. The sample comprised 1323 residents in 275 facilities in eight
      districts. The measures of service use were number of days in hospital and number
      of other service contacts. There were highly significant differences between
      facilities with similar levels of staffing managed by different agencies.
      Residents in the voluntary sector used fewer community services overall;
      residents in low-staffed local authority facilities used more services than those
      in similar facilities managed by other agencies. These differences were not
      easily explained by differences in the social or clinical characteristics of
      residents. This suggests that there may be organisational factors, e.g. hostel
      staff, knowledge of services, which influence access to and use of community
      services.

PMID- 9780815
TI  - Differential validity of informant-based diagnoses of dementia and depression in
      index subjects and in their first-degree relatives.
AB  - There is no study indicating that informant-derived information on dementia and
      depression (i.e. family history information) is equivalently valid for first
      degree relatives and for index subjects (i.e. patients and control subjects).
      However, this unproven assumption is the basis for the frequent, possibly
      inappropriate, use of instruments validated for patients and control subjects in
      family studies which focus on frequencies of psychiatric disorders in first
      degree relatives. Consequently, there is a need to compare the validity of family
      history information for both disorders in index subjects and their first-degree
      relatives. Validity was assessed by comparison of family history information for
      dementia and depression with interview-derived diagnoses in 75 index subjects and
      195 age-matched first-degree relatives. The validity of informant-derived
      information varied for different disorders, i.e. dementia and depression, and
      different samples, i.e. index subjects and first-degree relatives. In agreement
      with the study hypothesis, the sensitivity of surrogate information on dementia
      was significantly reduced in first-degree relatives in comparison with index
      subjects. In contrast, the sensitivity to detect depression was equivalent in
      subjects and in relatives. The results indicate the necessity to assess the
      validity of the psychiatric diagnoses of interest in the sample of interest, e.g.
      dementia or depression in first-degree relatives of patients and of control
      subjects. Observations in selected samples, i.e. subjects treated, hospitalised
      and/or autopsied, cannot be generalised to first-degree relatives in family
      studies.

PMID- 9780817
TI  - Will your patient admit "he hits me"?
AB  - Family violence is typically progressive. As a man realizes the effectiveness of
      physical and emotional coercion, he tends to use it more frequently. In the face
      of imbalance of power in the relationship, a victim becomes more fearful, more
      submissive, and more likely to face serious injury. This is the first of a two
      part series on physicians helping patients cope with domestic violence.

PMID- 9780816
TI  - Differential patterns of mental disorders among the homeless in Madrid (Spain)
      and Los Angeles (USA).
AB  - In this paper we compare rates of mental disorders (major depression, dysthymia,
      cognitive impairment, and schizophrenia) among homeless people in Madrid and Los
      Angeles (LA) and examine the ordering of the onset of both conditions (i.e.,
      homelessness and mental disorders). In the Madrid study, 262 homeless persons
      were interviewed using the CIDI. In the LA study, 1563 homeless persons were
      interviewed with the DIS. To make an item-by-item comparison, we companied the
      databases from both studies to submit a single database to statistical analyses.
      Results showed no significant differences in DSM-III-R life-time prevalence rates
      of mental disorders between both samples. However, the Madrid sample showed
      higher 12-month prevalence rates of dysthymia and cognitive impairment as
      compared to the LA sample. Most subjects across both cities first experienced
      symptoms of their mental disorders before first becoming homeless. The only
      significant difference was that all of the depressed adults in Madrid experienced
      depression prior to first becoming homeless, whereas this was the case for only
      59.1% of LA depressed homeless people. We discuss the reasons for these cultural
      differences and their implications for cross-national public health research and
      intervention.

PMID- 9780818
TI  - What physicians should know about employment contracts.
AB  - If the contract does not provide the physician the right to amend or terminate
      the agreement--even when the employer has clearly breached the contract--the
      physician may have to choose between living with the present situation or suing
      for damages.

PMID- 9780819
TI  - A perspective on financial incentives in health care.

PMID- 9780821
TI  - Ventricular myxoma presenting as acute visual loss.
AB  - We report a case of left ventricular myxoma with embolization to the left
      posterior cerebral artery, causing acute visual loss. The tumor was successfully
      resected and a follow-up echocardiography after 21 months revealed no evidence of
      tumor recurrence. The patient also had a past history of testicular seminoma. We
      believe that this is the first case report of an association of cardiac myxoma
      and testicular seminoma.

PMID- 9780820
TI  - Loss prevention case of the month. Patient care is a collaborative effort.

PMID- 9780822
TI  - Preventive medicine in geriatrics.

PMID- 9780824
TI  - Vanderbilt morning report. A case of alcoholic ketoacidosis.

PMID- 9780823
TI  - Department of Health & report. The Tennessee State Hemophilia Program.

PMID- 9780825
TI  - Clinical, clinico-pathological and serological studies of Babesia ovis in
      experimentally infected sheep.
AB  - Clinical, clinico-pathological and serological studies were performed in sheep
      experimentally infected with Babesia ovis. Acute babesiosis occurred in all the
      lambs infested with adult Rhipicephalus bursa ticks and in one lamb infested with
      the larvae. The rate of parasitaemia and the degree of anaemia were not
      correlated. Decrease in the packed-cell volume ranged from 30 to 40%. Parasitized
      erythrocytes were not observed to block capillaries in the brain, which explained
      the absence of nervous symptoms in acute babesiosis. The kidneys were the most
      severely affected organs, exhibiting acute glomerulonephritis. The lesions
      observed were suggestive of vascular alteration and vascular stasis, leading to
      anoxia of the tissues. A disseminated intravascular coagulation (DIC) syndrome
      was recorded in sheep infected with babesiosis. A marked increase in the enzymes
      of the transaminase groups, mainly aspartate aminotransferase (AST), was
      observed. Enzymatic changes (increases in AST, alanine aminotransferase (ALT) and
      lactic dehydrogenase (LDH) and decreases in sorbitol dehydrogenase (SDH),
      alkaline phosphatase (ALP) and malic enzyme (MEZ)), decreases in total proteins
      and albumin, and increases in urea and creatinine might reflect the degree of
      severity of the damage to the liver and kidney tissues. Most of the lambs (85%)
      that were infested with larvae, and all lambs infested with adult R. bursa ticks,
      reacted serologically to B. ovis antigen. The serological reactions following
      infestation with the larvae occurred much later than those following infestation
      with the adult stage. The lambs which were infested with larvae showed mild
      clinical reactions when challenged by infected R. bursa adults, as compared with
      the reactions to the challenge in naive control animals. The serological
      findings, in addition to the fact that one splenectomized lamb reacted to larval
      infestation with acute ovine babesiosis, show that the preimaginal stages of R.
      bursa can transmit B. ovis, usually causing a sub-clinical disease. It is
      suggested that infections derived from preimaginal ticks in the winter can
      preimmunize sheep for the subsequent more severe infections derived from adult
      ticks in the summer. Furthermore, in the absence of a reliable vaccine against B.
      ovis, grazing flocks in the enzootic regions should be exposed to the preimaginal
      stages during their activity period (October-February) before exposure to the
      adult ticks in spring and summer (April-July).

PMID- 9780826
TI  - Direct detection of Mycobacterium tuberculosis complex and M. avium complex in
      tissue specimens from cattle through identification of specific rRNA sequences.
AB  - Mycobacterium Tuberculosis Direct test and Accuprobe M. avium Complex test, rely
      on recognition of specific rRNA sequences. The present investigation included
      sequentially a pre-evaluation study and a study on non-visible lesion tuberculin
      reactor cattle. As regards the first study, tests were performed on tissue
      samples from 14 reactors with tuberculous-like lesions and from as many lesion
      free non-reactors, using culture findings as a reference. MTD and Accuprobe M.
      Avium Complex tests proved positive in 12 and 2 reactors respectively. Both tests
      proved negative in all non-reactors. Data consisted with culture findings. The
      aim of the second study was to verify the presence of mycobacteria in lymph node
      and tonsil homogenates from 32 non-visible lesion cattle. MTD and Accuprobe M.
      avium Complex test proved positive in 10 and 14 subjects respectively; no overlap
      was found. Our research demonstrates that low to minimal amounts of the main
      pathogenic mycobacteria can be reliably identified from cattle tissues by
      commercially available tests, which give simple, more rapid results than
      conventional techniques.

PMID- 9780827
TI  - Myocarditis associated with Theileria spp. in calves.
AB  - Two 3-week-old Limousin x Retinta calves from extensive farms in the south of
      Spain died suddenly. Microscopic examination of the spleen and lymph nodes
      revealed an intense lymphoid proliferation; the germinal centres were prominent
      and were surrounded by areas of haemorrhage. Parasitic forms, similar to Koch's
      bodies, were observed in only a small number of lymphoid cells and macrophages.
      In the myocardium a severe myocarditis was found. Inflammatory cells were in
      close contact with damaged myocytes, sometimes surrounding fragments of cells. In
      some areas the vessels had intraluminal deposits of fibrin. The endothelial
      damage and thrombosis may have contributed to the damage observed in the
      myocytes, together with the cytotoxic mechanism associated with the presence of
      an intense inflammatory infiltrate. The active multiplication of parasites may be
      due to the age of the animals and their breed, since they are not an
      autochthonous breed and present low resistance to infection.

PMID- 9780828
TI  - Use of the protective antigen of Erysipelothrix rhusiopathiae in the enzyme
      linked immunosorbent assay and latex agglutination.
AB  - To establish a safe and convenient serodiagnostic method for swine erysipelas, a
      purified protective protein antigen of Erysipelothrix rhusiopathiae, which
      included a large amount of protective protein (64 kDa protein), was used for
      enzyme-linked immunosorbent assay (ELISA) and the latex agglutination (LA) test.
      In the ELISA, the antisera to four different serovars (1a, 2, 5 and 20) of E.
      rhusiopathiae exhibit a positive reaction, while antisera to other species of
      bacteria (Listeria monocytogenes, Staphylococcus aureus, Streptococcus suis,
      Rhodococcus equi and Corynebacterium pseudotuberculosis) exhibit a negative
      reaction. In the LA test, the antisera to three different serovars (1a, 2 and 5)
      of E. rhusiopathiae reacted with P64-sensitized latex beads, while the antiserum
      to serovar 20 (2553 strain) did not. Moreover, the antisera to other species of
      bacteria (Listeria monocytogenes, Staphylococcus aureus, Streptococcus suis,
      Rhodococcus equi and Corynebacterium pseudotuberculosis) did not in this test.
      Comparing the results of the growth agglutination (GA), ELISA and LA tests of 284
      swine sera, there was a high degree of correlation among the results. The
      detection of anti-E. rhusiopathiae antibodies in the GA, ELISA and LA tests were
      compared using sera from pigs immunized with P64, alkaline extract (AE) and live
      cell vaccine (LV). In all three tests, anti-E. rhusiopathiae antibodies could be
      detected 1 week after immunization. The serum antibody titre as determined by the
      LA test increased moderately, as did that by the GA test, while that determined
      by ELISA increased rapidly. These results suggested that ELISA could be used to
      monitor changes in anti-E. rhusiopathiae antibody titre and the LA test could be
      used in the screening test for swine erysipelas.

PMID- 9780829
TI  - Evaluation of a commercial ELISA test for the detection of allergen-specific IgE
      antibodies in atopic dogs.
AB  - A commercial enzyme-linked immunosorbent assay (ELISA) designed to detect
      allergen-specific immunoglobulin (Ig)E antibodies were evaluated in 36 atopic
      dogs and in 12 normal dogs. The test showed a sensitivity of 72.23% and a
      specificity of 41.6%. Positive and negative predictive values were 76.47 and
      35.71% respectively. Correlation between the ELISA kit results and intradermal
      skin testing varied depending on the allergen and ranged from 47.1 to 80.4%,
      although positive correlation (i.e. allergens positive in both tests) ranged rom
      2.7 to 19.4%. In conclusion, this serological test gave both false positive and
      false negative results. Sensitivity, specificity and predictive values indicate
      that this ELISA may not be useful in canine atopy. Although correlation studies
      were hampered by the impossibility of using the same allergenic extracts, the
      correlation observed between intradermal and serological testing indicates that
      results from both tests are not interchangeable.

PMID- 9780830
TI  - Macrophages in the chicken oviduct: morphometrical studies by light and
      transmission electron microscopy and the possible influence of sex hormones.
AB  - Light and electron microscopic techniques were used to study the morphometry and
      dynamic changes of macrophages in the postnatal and sex hormone-treated chicken
      oviduct, respectively. Abundant typical macrophages, containing clear vacuoles,
      well-developed mitochondria, Golgi complexes and lysosomal bodies in their
      cytoplasms, were observed in the lamina propria of all segments of the postnatal
      chicken oviduct, occurring more frequently in the vaginal part. When 7-day-old
      chickens were injected with diethylstilbestrol (DES), and DES plus progesterone,
      infiltration of a significant number of macrophages in both groups, but not in
      controls could be seen. The light and electron microscopic structures of the
      macrophages in both postnatal and sex hormone-treated chicken oviduct were
      similar. These results show that typical macrophages are present in the chicken
      oviduct; their frequency of occurrence varies with different oviductal segments,
      and they are influenced by sex hormones.

PMID- 9780831
TI  - Relationship between abortions and seroprevalences to selected infectious agents
      in dairy cows.
AB  - The aim of this study was to determine whether the occurrence of abortion is
      related to the seroprevalence of abortion-causing infectious agents. In a cross
      sectional study, cattle from dairy farms in Switzerland that were defined as
      having an abortion problem were divided into two groups: cows with a history of
      abortion within the previous 3 months (cases) and cows without a history of
      abortion (controls). A positive titre to Leptospira spp. was associated with an
      increased probability of being a case (OR = 1.74, 95% CI = 1.21-2.47). There were
      interactions between Coxiella burnetti titre and parity, and between Chlamydia
      psittaci and C. burnetti titre and breed. Multiparous cases after the second
      lactation with a positive titre to C. burnetti were less likely (OR = 0.42, 95%
      CI = 0.22-0.82) to be cases. Swiss Browns (Swiss Braunvieh and Brown Swiss) with
      a positive titre to C. psittaci and Swiss Browns with a positive titre to C.
      burnetti were more likely (OR = 1.63, 95% CI = 1.13-2.37 and OR = 1.79, 95% CI =
      1.15-2.78, respectively) to be cases. Parity alone was not associated with the
      occurrence of abortion.

PMID- 9780832
TI  - Haemorrhagic septicaemia by Aeromonas salmonicida subsp. salmonicida in a black
      tip reef shark (Carcharhinus melanopterus).
AB  - One black-tip reef shark (Carcharhinus melanopterus) was found dead without
      previous signs of disease. Major lesions consisted in cutaneous erythema, mainly
      at the base of the fins, focal to diffuse inflammatory lesions in gills and
      intestinal wall, and discrete haemorrhages in the same organs, liver and kidneys.
      Microcolonies of Gram-negative rods were observed in the lamina propia of gills,
      underneath the intestinal mucosa and randomly distributed in the renal and
      hepatic parenchymas. Also, emboli containing Gram-negative rods were observed in
      capillaries of these organs. Aeromonas salmonicida subsp. salmonicida was
      isolated in pure culture from gills, liver and intestine. Specific immunostaining
      confirmed the relationship between the isolate and lesion-associated bacteria. No
      previous reports on this infection in sharks have been found in the literature.

PMID- 9780833
TI  - Melanocortin receptors and antagonists regulate pigmentation and body weight.
AB  - The action two genetic loci--agouti and the melanocortin receptor-1 (Mc1r)-- have
      opposing effects in the control of mammalian pigmentation and ultimately
      determine the color of the pigment produced. In a recent paper, Ollmann et al.
      confirmed that the agouti protein acts via the Mc1r. They show that high-affinity
      binding of the agouti protein to Mc1r expressed in mammalian cells can be
      inhibited by the receptor's natural ligand, alpha-melanocyte-stimulating hormone
      (alpha-MSH). In addition, genetic studies using mice carrying mutations at the
      Mc1r and agouti loci on a sensitized background of low tyrosinase expression
      confirm that a functional Mc1r is required for the maximum pigmentary effect of
      agouti. Thus, the Mc1r appears to be a unique, bifunctionally controlled
      receptor, activated by alpha-MSH and antagonized by agouti, both of which
      contribute to the variability seen in mammalian coat color.

PMID- 9780834
TI  - CaM kinase II as frequency decoder of Ca2+ oscillations.
AB  - In many cell types, Ca2+ signals are organized in the form of repetitive spikes.
      The frequency of these intracellular Ca2+ oscillations increases with the level
      of stimulation, suggesting the existence of a frequency encoding phenomenon. The
      question arises as to how the frequency of Ca2+ oscillations can be decoded
      inside the cell. Ca2+/calmodulin kinase II has long been proposed as an
      attractive candidate, as it is a key target of Ca2+ signals. By immobilizing the
      Ca2+/calmodulin kinase II and subjecting it to pulses of Ca2+ of variable
      amplitude, duration, and frequency, De Koninck and Schulman have shown for the
      first time that the autonomous activity of Ca2+/calmodulin kinase II is highly
      sensitive to the temporal pattern of Ca2+ oscillations.

PMID- 9780835
TI  - The hemangioblast--an elusive cell captured in culture.
AB  - The close temporal and spatial association between blood and endothelial cell
      development during embryogenesis was first documented almost 100 years ago. In
      recent years, gene expression studies have further strengthened this link. Now,
      using cultures of mouse embryonic stem cells, a common progenitor cell that gives
      rise to both blood cells and vascular endothelial cells, has been identified. The
      existence of the hemangioblast has been proved and experiments addressing its
      unique properties can begin.

PMID- 9780836
TI  - Roles of histone acetyltransferases and deacetylases in gene regulation.
AB  - Acetylation of internal lysine residues of core histone N-terminal domains has
      been found correlatively associated with transcriptional activation in eukaryotes
      for more than three decades. Recent discoveries showing that several
      transcriptional regulators possess intrinsic histone acetyltransferase (HAT) and
      deacetylase (HDAC) activities strongly suggest that histone acetylation and
      deacetylation each plays a causative role in regulating transcription.
      Intriguingly, several HATs have been shown an ability to acetylate nonhistone
      protein substrates (e.g., transcription factors) in vitro as well, suggesting the
      possibility that internal lysine acetylation of multiple proteins exists as a
      rapid and reversible regulatory mechanism much like protein phosphorylation. This
      article reviews recent developments in histone acetylation and transcriptional
      regulation. We also discuss several important, yet unanswered, questions.

PMID- 9780837
TI  - Genetics of susceptibility to Theiler's virus infection.
AB  - Theiler's virus is a picornavirus of mouse which causes an acute
      encephalomyelitis followed by a persistent infection of the white matter
      resulting in chronic inflammation and demyelination. This disease has been
      studied as a model for multiple sclerosis. Inbred strains of mice are either
      resistant--they clear the infection after the acute encephalomyelitis--or
      susceptible to persistent infection and demyelination. Susceptibility is a
      polygenic trait which has been analyzed using methods of association with
      "candidate" genes, and linkage analysis after a complete genome scan. The H-2Db
      gene is responsible for an efficient CTL response which makes some strains
      resistant. Non H-2 genes responsible for the susceptibility of other strains have
      been mapped by linkage analysis to the lfng and, possibly, the Mbp loci. The
      analysis of a set of congenic mice ruled out the possibility that the relevant
      gene codes for interferon gamma, and showed that the region around lfng probably
      contains two susceptibility genes. The analysis of mutant mice showed further
      that the Mbp gene, which codes for the myelin basic protein, has a major effect
      on viral persistence.

PMID- 9780838
TI  - Unraveling the role of helicases in transcription.
AB  - Proteins with seven conserved "helicase domains" play essential roles in all
      aspects of nucleic acid metabolism. Deriving energy from ATP hydrolysis,
      helicases alter the structure of DNA, RNA, or DNA:RNA duplexes, remodeling
      chromatin and modulating access to the DNA template by the transcriptional
      machinery. This review focuses on the diverse functions of these proteins in the
      process of RNA polymerase II transcription in eukaryotes. Known or putative
      helicases are required for general transcription initiation and for transcription
      coupled DNA repair, and may play important roles in elongation, termination, and
      transcript stability. Recent evidence suggests that helicase-domain-containing
      proteins are also involved in complexes that facilitate the activity of groups of
      seemingly unrelated genes.

PMID- 9780839
TI  - Glucagon-like peptide-1 (GLP-1): a gut hormone of potential interest in the
      treatment of diabetes.
AB  - GLP-1 (glucagon-like peptide-1) is a gut hormone which is released into the blood
      stream after feeding. Its main action is to stimulate insulin secretion through
      potentiating the insulinotropic action of glucose. The peptide is encoded in the
      glucagon gene and expressed mainly in the gut L cells. It exerts its actions
      through activating specific receptors of the seven transmembraneous domain-G
      protein-coupled type with 463 amino acids. Its main signalling mechanism is
      activation of adenylate cyclase and formation of cyclic AMP. The peptide also
      increases the cytoplasmic concentration of Ca2 which is thought to be executed
      both through a Na(+)-dependent uptake of extracellular Ca2+ and through release
      of Ca2+ from intracellular Ca2+ stores. GLP-1 also inhibits glucagon secretion
      and inhibits gastric emptying and gastric acid and pancreatic exocrine secretion.
      Its integrated action on carbohydrate metabolism results in reduction of
      circulating glucose, and GLP-1 has therefore been suggested as a therapeutic
      alternative in diabetes. Finally, GLP-1 is also expressed in neurons in the
      hypothalamus, and may be involved in the regulation of feeding behaviour, since
      it inhibits food intake.

PMID- 9780840
TI  - Nuclear domain 10, the site of DNA virus transcription and replication.
AB  - Within the highly organized nuclear structure, specific nuclear domains (ND10)
      are defined by accumulations of proteins that can be interferon-upregulated,
      implicating ND10 as sites of a nuclear defense mechanism. Compatible with such a
      mechanism is the deposition of herpesvirus, adenovirus, and papovavirus genomes
      at the periphery of ND10. However, these DNA viruses begin their transcription at
      ND10 and consequently initiate replication at these sites, suggesting that
      viruses have evolved ways to circumvent this potential cellular defense and
      exploit it. Other ND10-associated proteins belong to ubiquitin-related pathways.
      These findings, together with the accumulation of various overexpressed cellular
      and viral proteins, suggest that ND10 function as nuclear dumps or as nuclear
      depots. Consistent with the recruitment or deposition of various proteins and
      viral genomes adjacent to ND10, ND10 themselves may only be protein accumulations
      at specific but as yet undefined nuclear deposition sites. The concept of
      specific nuclear deposition sites may explain the juxtaposition of various
      nuclear bodies and allows testable predictions about a potential supramolecular
      regulatory mechanism whereby proteins are selectively segregated or released by
      global changes induced in nuclear functions such as viral infections, stress, or
      hormonal induction.

PMID- 9780841
TI  - Neural cell adhesion molecule L1: relating disease to function.
AB  - Neural cell adhesion molecules of the immunoglobulin superfamily are important
      components of the network of guidance cues and receptors that govern axon growth
      and guidance during development. For neural cell adhesion molecule L1, the
      combined application of human genetics, knockout mouse technology, and cell
      biology is providing fundamental insight into the role of L1 in mediating
      neuronal differentiation. Disease-causing mutations as well as mouse models of L1
      disruption can now be used to examine the relevance of L1 binding specificities
      and signal transduction pathways that have been observed in vitro.

PMID- 9780842
TI  - Eggs and embryos from the Cambrian.
AB  - The early evolution of metazoans is a major focus of biological attention, but is
      the historical record revealed in the Cambrian "explosion" an accurate reflection
      of original events? The key questions concern the nature of the earliest animals
      and when they originated. One widely-mooted suggestion is that planktotrophic
      larvae, typified by the annelidan trochophore and echinoid pluteus, existed long
      before the metazoan radiations evident in the Cambrian fossil record. This idea
      could be consistent for recent evidence of divergence times, based on molecular
      "clocks," of phyla appearing well before the Cambrian. Now a surprising new
      discovery of eggs with blastomeres and embryos with well-defined anatomy from the
      Cambrian (c.530 Myr ago) of China and Siberia promises to extend the arena of
      debate. In one case a convincing ontogeny can be traced from eggs to adult tube
      dwelling cnidarians. In the other example a possible protostome, unhatched and
      wrapped around the egg, shows segmentation and possibly nascent sclerites. In
      both, these cases development is direct, i.e., there is no evidence for any
      planktotrophic larval stage. The implications for our perceptions of both the
      Cambrian 'explosion' and metazoan phylogeny could be considerable.

PMID- 9780843
TI  - From "magic bullet" to "specially engineered shotgun loads": the new genetics and
      the need for individualized pharmacotherapy.
AB  - Steady progress in the identification of human pharmacogenetic variants and new
      discoveries of disease susceptibility genes makes the old notion of one
      disease/one drug untenable. Advances in the ability to rapidly identify these
      variants, when coupled with appropriate drug delivery systems, should
      revolutionize pharmacotherapy.

PMID- 9780844
TI  - Indoor climate and air quality. Review of current and future topics in the field
      of ISB study group 10.
AB  - In industrialized countries about 90% of the time is spent indoors. The ambient
      parameters affecting indoor thermal comfort are air temperature and humidity, air
      velocity, and radiant heat exchange within an enclosure. In assessing the thermal
      environment, one needs to consider all ambient parameters, the insulating
      properties of the occupants' clothing, and the activity level of the occupants by
      means of heat balance models of the human body. Apart from thermal parameters,
      air quality (measured and perceived) is also of importance for well-being and
      health in indoor environments. Pollutant levels are influenced by both outdoor
      concentrations and by indoor emissions. Indoor levels can thus be lower (e.g. in
      the case of ozone and SO2) or higher (e.g. for CO2 and formaldehyde) than outdoor
      levels. Emissions from cooking play an important role, especially in developing
      countries. The humidity of the ambient air has a wide range of effects on the
      energy and water balance of the body as well as on elasticity, air quality
      perception, build-up of electrostatic charge and the formation or mould. However,
      its effect on the indoor climate is often overestimated. While air-handling
      systems are commonly used for achieving comfortable indoor climates, their use
      has also been linked to a variety of problems, some of which have received
      attention within the context of "sick building syndrome".

PMID- 9780845
TI  - A comparative analysis of heat waves and associated mortality in St. Louis,
      Missouri--1980 and 1995.
AB  - This research investigates heat-related mortality during the 1980 and 1995 heat
      waves in St. Louis, Missouri. St. Louis has a long history of extreme summer
      weather, and heat-related mortality is a public health concern. Heat waves are
      defined as days with apparent temperatures exceeding 40.6 degrees C (105 degrees
      F). The study uses a multivariate analysis to investigate the relationship
      between mortality and heat wave intensity, duration, and timing within the summer
      season. The heat wave of 1980 was more severe and had higher associated mortality
      than that of 1995. To learn if changing population characteristics, in addition
      to weather conditions, contributed to this difference, changes in population
      vulnerability between 1980 and 1995 are evaluated under simulated heat wave
      conditions. The findings show that St. Louis remains at risk of heat wave
      mortality. In addition, there is evidence that vulnerability has increased
      despite increased air-conditioning penetration and public health interventions.

PMID- 9780846
TI  - Pituitary-gonadal hormones during prolonged residency in Antarctica.
AB  - Plasma luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin
      (PRL) and testosterone levels were measured in nine eugonadal men in New Delhi
      and during the 1st week of different months of their stay at Dakshin Gangotri in
      Antarctica. During their 12-month stay in Antarctica, they were exposed to a
      severely cold climate, long polar nights and polar days, high wind velocity,
      increased amounts of solar and ultraviolet radiation and geomagnetism, as well as
      physical and social isolation. Plasma testosterone tended to increase in March,
      but a significant increase (P < 0.05) was not seen until April. The mean
      testosterone levels in May, June, September and November were also significantly
      higher than the March or New Delhi values. The absolute values of LH, FSH and PRL
      did not show any month-to-month changes in Antarctica. However, when the hormone
      levels were expressed as a percentage of the individual annual Antarctic mean,
      significant differences as a percentage of the individual annual Antarctic mean,
      significant differences were observed. The testosterone peak in April, May and
      June was associated with an increase in LH. The nadirs of testosterone, LH, FSH
      and PRL were seen in either July or August. FSH showed the highest values in
      March, whereas the highest PRL values were seen in November. These observations
      suggest the presence of circannual variations in gonadotropin, PRL and LH in
      Antarctica which are independent of polar days and polar nights. It appears that
      factors other than the duration of daylight might be involved in regulating these
      changes. The significance of maintenance of testosterone levels in the supra
      physiological range in Antarctica remains unknown but may be important in
      acclimatization/habituation to the extreme polar cold by increasing basal
      metabolic rate, protein synthesis and erythropoiesis.

PMID- 9780847
TI  - Effect of hypobaric hypoxia on immune function in albino rats.
AB  - The effect of exposure to hypoxia on macrophage activity, lymphocyte function and
      oxidative stress was investigated. Hypoxia enhanced peritoneal macrophage
      activity as revealed by enhanced phagocytosis and free radical production. There
      was no significant change in antibody titres to sheep red blood cells in either
      serum or spleen during hypoxia. However, there was a considerable reduction in
      the delayed-type hypersensitivity response to sheep red blood cells, indicating
      the impairment of T-cell activity. Hypoxia decreased the blood glutathione
      (reduced) level and increased plasma malondialdehyde by a factor of about 2. It
      is therefore speculated that hypoxia imposes an oxidative stress leading to
      decreased T-cell acivity.

PMID- 9780848
TI  - Gadolinium-enhanced MR angiography of the carotid arteries.
AB  - To assess the efficacy of gadolinium (Gd)-enhanced magnetic resonance angiography
      (gdMRA) in overcoming signal dropout artifacts on conventional MRA (cMRA), the
      authors examined 13 patients with suspected neurovascular stenotic/occlusive
      lesions on MRA pre- and post-gadolinium enhancement. The sample consisted of 18
      internal carotid artery (ICA) les ons (16 extracranial, 2 cranial). In 13 of 16
      stenotic vessels, gdMRA better characterized the pathoanatomy of moderate to
      severe stenotic lesions, changing MRA diagnosis in 3 patients. In zero of three
      vessels with no flow enhancement by cMRA, the lumen remained nonvisualized on
      gdMRA. For an ICA lesion at the skull base, enhancement of surrounding normal
      structures limited the usefulness of the technique. The authors conclude that Gd
      MRA is a fast, accurate, and convenient noninvasive technique for documenting the
      morphology and severity of carotid stenotic disease, especially extracranially.

PMID- 9780849
TI  - Blood flow velocities in three cerebral arteries in the same subjects modulate
      during thinking.
AB  - College students (n = 22) engaged in thinking activities while simultaneous
      bilateral velocity (V) measures are obtained from their middle, anterior, and
      posterior cerebral arteries (MCA, ACA, and PCA). The study follows a 3 x 2 x 6
      factorial design with repeated measures on artery insonated (MCA, ACA, and PCA),
      hemisphere (right and left), and six experimental phases, within which an initial
      62-second baseline (BL) period is followed by five 31-second thinking tasks
      (short-term remembering, generating an image, making decisions, and solving
      language and math problems). VMCA is faster than BL during each thinking task
      (range, 4.9%-8.5%; p < 0.001), but changes in VACA, VPCA, and all hemispheric
      differences are not significant. A stronger degree of increase is present for
      VMCA than (1) both VACA and VPCA during short-duration remembering, making
      decisions, and working math problems, and (2) VACA, which in turn is stronger
      than VPCA when generating images and constructing new words. The authors' study
      shows that transcranial Doppler neuroimaging conveniently provides physiological
      indices of thinking from three cerebral arteries of the same subjects.

PMID- 9780850
TI  - Cerebral effects of a single dose of intravenous vinpocetine in chronic stroke
      patients: a PET study.
AB  - The effects of vinpocetine (Cavinton) on the cerebral glucose metabolism of
      chronic stroke patients are studied with positron emission tomography. The
      regional and global cerebral metabolic rates of glucose (CMRglu) and the kinetic
      constants related to them are quantified before and after single-dose intravenous
      vinpocetine treatment. These measurements are completed with transcranial Doppler
      sonography and single photon emission computed tomography to explore the possible
      mechanisms underlying the resulting changes in glucose uptake and metabolism in
      the brain. The authors' findings indicate that a single-dose vinpocetine
      treatment, although it does not affect significantly the regional or global
      metabolic rates of glucose, improves significantly the transport of glucose (both
      uptake and release) through the blood-brain barrier in the whole brain, the
      entire contralateral hemisphere, and in the brain tissue around the infarct area
      of the symptomatic hemisphere. These changes are in accord with increased blood
      flow in the entire contralateral hemisphere as well as decreased blood flow
      velocity and increased peripheral vessel resistance in the entire symptomatic
      hemisphere.

PMID- 9780851
TI  - PET and CBF studies of chronic hydrocephalus: a contribution to surgical
      indication and prognosis.
AB  - The authors investigate whether measurement of cerebral blood flow (CBF) in
      chronic hydrocephalus is a reliable indicator in selecting patients to undergo
      ventriculoperitoneal shunting. Global and regional CBF is quantified (Kety
      Schmidt one-compartment model) by positron emission tomography in 21 patients.
      CBF is determined following injection of 15O-H2O at three time points: 1 week
      before, 7 days after, and 7 months after shunting. The neurological status of
      these patients is classified, and cerebrospinal fluid (CSF) dynamics continuous
      intracranial pressure [ICP] monitoring and CSF infusion tests) were assessed
      prior to surgery. Preoperative global CBF values correlate well with clinical
      outcome. Patients with a significantly lower global CBF value show clinical
      improvement after 7 months, whereas patients with higher CBF values do not (mean,
      33 vs. 45 ml/100 ml per minute; p < 0.05). In contrast to conventional methods,
      including long-term ICP measurement and CSF infusion tests, preoperative global
      CBF values are discriminating in terms of clinical outcome. Thus, measurement of
      CBF may be helpful in evaluating the ultimate utility of shunt therapy in chronic
      hydrocephalus.

PMID- 9780852
TI  - Cerebral venous infarctions presenting as enhancing space-occupying lesions: MRI
      findings.
AB  - Cerebral venous thrombosis is an unusual form of cerebrovascular disease that may
      cause cerebral venous infarction (CVI). Magnetic resonance imaging (MRI) of the
      brain may improve the often elusive diagnosis of CVI. However, the sensitivity,
      specificity, and full spectrum of such MRI findings are poorly understood. The
      authors present the cases of three patients with CVI whose MRI scans showed
      abnormally enhancing tumor-like brain lesions. Two of the CVIs were hemorrhagic
      and exerted mass effect. One patient showed increasingly nodular and
      heterogeneous ring-like enhancement progressing from the single-dose to the
      triple-dose gadolinium contrast images. The CVI of a second patient also showed
      ring-like enhancement. Biopsy was performed on one of these patients and was
      strongly considered for the other two patients to exclude neoplastic disease.
      Careful examination of the MRI appearance of venous structures and the use of
      specialized MRI techniques improved the recognition of CVI for two patients and
      prevented biopsy. This represents the first description of abnormal triple-dose
      MRI contrast enhancement in CVI. Consideration of CVI in the care of patients
      with enhancing tumor-like masses may lead to earlier diagnosis and treatment,
      preventing unnecessary invasive diagnostic procedures. CVI should be added to the
      differential diagnosis of supratentorial ring-enhancing masses.

PMID- 9780853
TI  - Age-related changes of the insular cortex and lateral ventricles: conventional
      MRI volumetric measures.
AB  - Preliminary data suggest that the insular region may be atrophied in patients
      with Alzheimer's disease when compared with healthy, age-matched control
      subjects. Therefore, normative data on age-related changes of the insular cortex
      were gathered and compared with age-related changes in the bodies of the lateral
      ventricles, which have been studied previously. Cerebrospinal fluid (CSF) volume
      of the lateral ventricles and insular cortical regions were measured on T1
      weighted axial magnetic resonance images in 93 healthy subjects (age 21 to 84
      years). Age-related changes were found in the lateral ventricles (r = 0.57, p <
      0.0001) and in the CSF insular space (r = 0.42, p < 0.0001). Increasing age
      accounted for a significant amount of the variance for the lateral ventricle (pc
      = 0.45, p < 0.0001), but not for the insula (pc = 0.15, p = 0.14). Although there
      was a continuous linear increase in lateral ventricular volume with age, the CSF
      insular space increased linearly until the fourth decade, then plateaued until
      the seventh decade, with a linear increase thereafter. These data suggest that
      age-related changes occur in the region of the insular cortex, but differ from
      age-related changes of the lateral ventricles.

PMID- 9780854
TI  - A 67-year-old woman with polymyalgia rheumatica and left hemispatial neglect.
AB  - A 67-year-old woman with a diagnosis of polymyalgia rheumatica presented
      initially with periods of confusion and incontinence. A CT scan of the brain was
      normal and she was treated with tapering doses of corticosteroids and clinical
      improvement. After a brief period off steroids, the patient presented with a
      progressive dementia, left-sided clumsiness, gait disturbances and left
      hemispatial neglect. An MRI at this time demonstrated a large area of edema over
      the right parietal lobe and intense cortical enhancement. A chest CT demonstrated
      multiple nodules. Biopsies of the lung and brain failed to identify any
      infectious organisms or malignant tissue. The leptomeningeal biopsy revealed
      multiple granulomatous areas with central necrosis and hystiocytic cells
      consistent with idiopathic hypertrophic pachy-meningitis.

PMID- 9780855
TI  - High-resolution fluorodeoxyglucose positron emission tomography shows both global
      and regional cerebral hypometabolism in multiple sclerosis.
AB  - The authors study brain regional glucose metabolism prospectively in multiple
      sclerosis (MS) using high-resolution 2-[18-F]fluoro-2-deoxy-D-glucose positron
      emission tomography (FDG PET) in 25 MS patients of the Dent Neurologic Institute
      compared with 6 healthy subjects. Glucose metabolism is measured in 20 regions of
      interest using a line-profile technique. Compared with control subjects, a 9%
      reduction in total brain glucose metabolism is noted in MS patients (p < 0.05).
      Hypometabolism is widespread, including the cerebral cortex, subcortical nuclei,
      supratentorial white matter, and infratentorial structures. This reduction
      represents absolute regional decreases ranging from 3% to 18%. The most dramatic
      absolute reductions occur in the superior mesial frontal cortex, superior
      dorsolateral frontal cortex, mesial occipital cortex, lateral occipital cortex,
      deep inferior parietal white matter, and pons. The regional hypometabolism in the
      superior mesial frontal cortex and superior dorsolateral frontal cortex is
      statistically significant (p < 0.05), whereas the changes in the mesial occipital
      cortex (p = 0.07) and the lateral occipital cortex (p = 0.09) approach
      significance. The authors' findings suggest that widespread cerebral dysfunction
      occurs in MS, and that diaschisis or neuronal system disconnection resulting from
      white matter disease plays a major role. Cortical gray matter hypometabolism may
      also reflect direct MS involvement. The quantitative cerebral abnormalities
      detected by FDG PET may serve as a marker of disease activity in understanding
      the pathophysiological expression and therapeutic response of MS.

PMID- 9780856
TI  - Tortuosity of carotid and vertebral arteries: a magnetic resonance angiographic
      study.
AB  - Nine patients (group A) were found on magnetic resonance angiography (MRA) to
      have excessive carotid artery, vertebral artery, and vertebrobasilar junction
      tortuosity. A control group (group B) were age- and sex-matched to group A
      patients, were selected randomly from our MRA or stroke data banks, and had not
      undergone MRA for evaluation of migraine, "carotidynia," or pulsatile tinnitus.
      Factors more prevalent in group A patients included migraine, chronic daily
      headache, carotidynia, pulsatile tinnitus, and a positive family history of
      headache. Factors more prevalent in group B patients included a positive family
      history of stroke, large-vessel atherosclerosis, and scan evidence of ischemic
      infarctions; many group B patients had undergone MRA for stroke or transient
      ischemic attack evaluation. Men were slightly underrepresented at 44%, and were
      younger than women (34 +/- 6 years vs. 43 +/- 3 years; p = 0.01). Relationships
      in this preliminary study between arterial tortuosity and migraine seem evident.

PMID- 9780857
TI  - Transient blindness associated with reversible occipital white matter
      abnormalities: two patients studied by MR, CT, and 18F-FDG PET imaging.
AB  - Reversible, multifocal hyperintense T2 signal abnormalities were noted within the
      occipital and posterior parietal subcortical white matter in a previously healthy
      59-year-old right-handed woman with acute onset of cortical blindness and
      seizures. Repeat brain magnetic resonance imaging and a positron emission
      tomographic scan of 18F-fluorodeoxyglucose brain uptake performed 2 months after
      the ictal event failed to reveal any abnormality. This patient is similar to a 57
      year-old female who developed severe headache and magnetic resonance signal
      abnormalities in the subcortical white matter of both occipital lobes, which
      later normalized, as judged by correlative, sequential computed tomographic
      examinations. This study emphasizes that an increasingly more frequent phenomenon
      of reversible MRI signal abnormalities can occur within the occipital subcortical
      white matter in acutely ill individuals, and not be associated with any lasting
      abnormalities on clinical examination or on radiological imaging studies such as
      computed tomography, magnetic resonance imaging, or positron emission tomography.

PMID- 9780858
TI  - Engorged anterior epidural venous plexus mimics an anterior epidural mass.
AB  - A 48-year-old woman presented with severe neck pain on flexion 1 week after a
      reportedly uncomplicated lumbar puncture, and with a slightly elevated white
      blood cell count. Magnetic resonance imaging showed an anterior epidural mass
      that was thought to represent an epidural abscess. At surgery, the epidural
      "mass" was due to an engorged anterior epidural venous plexus.

PMID- 9780859
TI  - Internal carotid artery dissection causes hypoglossal nerve palsy: CT, MRI, and
      angiographic findings.
AB  - A case of unilateral XIIth nerve palsy due to the dissection of the internal
      carotid artery is reported. The clinical and radiological features are described.
      In this patient, cranial nerve palsy is probably the result of compression by an
      enlarging carotid artery due to mural hematoma. Diagnosis is discussed with
      emphasis on magnetic resonance imaging findings. Magnetic resonance imaging is
      also useful for follow-up of arterial lesions.

PMID- 9780860
TI  - Bilateral representation of language function. Agenesis of corpus callosum by
      Wada and PET activation.
AB  - A 33-year-old right-handed man with intermittent headache was found to have
      agenesis of the corpus callosum. He underwent magnetic resonance imaging,
      positron emission tomography (PET), and detailed neuropsychologic tests,
      including a Wada test. There was bilateral representation of language, and a PET
      activation study with word repetition revealed bilateral areas of activation that
      were not completely symmetric. These findings and the literature concerning
      agenesis of the corpus callosum are discussed as is the possible compensatory
      mechanism for absence of the corpus callosum, which is important for cross
      communication.

PMID- 9780861
TI  - Visual form of Alzheimer's disease and its response to anticholinesterase
      therapy.
AB  - In a 60-year-old woman with the visual variant of Alzheimer's disease, single
      photon emission computed tomography abnormalities were most marked in the parieto
      occipital regions of the brain. After treatment with donepezil, improvement is
      noted on neuropsychological testing and on brain SPECT, including increased
      perfusion (metabolism) in the occipital lobes.

PMID- 9780862
TI  - Stay stronger longer with weight training.

PMID- 9780863
TI  - Your best shot for a healthy winter.

PMID- 9780864
TI  - Clearing up confusion about hypertension drugs.

PMID- 9780865
TI  - Living with cancer but not with the pain.

PMID- 9780866
TI  - Can low blood pressure over a long period cause dizziness or extreme muscle
      weakness?

PMID- 9780867
TI  - I recently found out that the red rash on my nose and cheeks is due to rosacea,
      and my doctor prescribed an antibiotic. Will I have this condition for the rest
      of my life or can I be cured by the treatment?

PMID- 9780868
TI  - B vitamins and heart disease.

PMID- 9780869
TI  - Don't doze and drive.

PMID- 9780870
TI  - Viagra: beyond the jokes.

PMID- 9780871
TI  - Beyond cholesterol: clusters of risk factors.

PMID- 9780872
TI  - Soy--a perfect food?

PMID- 9780873
TI  - I am a 50-year-old male who has completed several marathons over the last 20
      years. At my last physical examination, my electrocardiogram came back with a
      reading of "sinus arrhythmia" and "incomplete right bundle branch block." My
      physician is not concerned about these findings, but should I be?

PMID- 9780874
TI  - I am having a heart bypass operation soon. How long will it be before I feel back
      to normal?

PMID- 9780875
TI  - My doctor says that I have calcium deposits around my aortic valve and these
      deposits are causing a heart murmur. Is there any treatment that can halt their
      progress or reverse this calcification?

PMID- 9780876
TI  - I take Adalat (or nifedipine, also sold as Procardia) and captopril tablets daily
      for my high blood pressure. My physician told me not to take aspirin because of
      the possibility of drug interactions. From what I have read about aspirin, I hate
      to miss out on the benefits.

PMID- 9780878
TI  - Chest pain. If it's not your heart, what's causing it?

PMID- 9780877
TI  - In the past 12 to 18 months, my level of anxiety has increased significantly. I
      have been on atenolol and simvastatin (Zocor) for the past couple of years. Is
      there anything in these drugs that could cause this anxiety?

PMID- 9780879
TI  - Health tips. Allergic reactions.

PMID- 9780880
TI  - Cigars aren't a safe alternative to cigarettes.

PMID- 9780881
TI  - Exercise and diet team up to fight cholesterol.

PMID- 9780882
TI  - Preventing low back pain. How to support what supports you.

PMID- 9780884
TI  - Garlic. The latest on this legendary herb.

PMID- 9780883
TI  - Surgery for obesity. When is it appropriate?

PMID- 9780885
TI  - I've heard there's a vaccine for pneumonia. How do I know if I need it?

PMID- 9780886
TI  - I recently read that some drugs are used for "off-label" purposes. What does that
      mean?

PMID- 9780887
TI  - A 6-year follow-up on cerinate porcelain veneers.

PMID- 9780888
TI  - A directed shrinkage approach to the provision of foundations for decimated
      teeth.
AB  - The directed shrinkage approach was developed to create sealed tooth-restoration
      interfaces in posterior composite restorations. Creative application of this
      technique can result in foundations that are suitable for a variety of
      applications, including salvaging broken-down teeth and supporting free-hand
      restorations. The sealed interface reduces microleakage and postoperative tooth
      sensitivity. The components required for this technique are readily available and
      are usually part of the practice's armamentarium.

PMID- 9780889
TI  - Clinical and microbiological aspects of the Sargon immediate load implant.
AB  - A maxillary lateral incisor with severe periodontal destruction was extracted
      after forced eruption and was replaced with a Sargon Immediate Load Implant. The
      clinical and microbiological results of the case are reported. The Sargon
      Immediate Load Implant is an apically expandable, quintapodal, root-form dental
      implant, designed to be loaded immediately with a provisional fixed restoration
      in normal occlusion.

PMID- 9780891
TI  - Dental handpiece sterilization: historical and technological advances.

PMID- 9780890
TI  - Craniofacial pain of myofascial origin: temporomandibular pain & tension-type
      headache.
AB  - Craniofacial pain of myofascial origin is a common chronic disorder. When the
      pain is unilateral and located periauricularly, masticatory myalgia is likely.
      Tension-type headache is usually bilateral and affects the upper part of the
      head. The possible interrelationship with generalized myofascial disorders are
      discussed. Practical approaches to history-taking, diagnosis, and treatment are
      suggested.

PMID- 9780892
TI  - Incisal edge reattachment: literature review and treatment perspectives.
AB  - Anterior crown fractures in children and adolescents are a common form of injury,
      affecting approximately 25% of that population. Common restorative treatments
      such as composite bonding, laminate veneers, or full-coverage restorations tend
      to sacrifice healthy tooth structure and challenge dentists to match the adjacent
      unrestored dentition. Incisal edge fragment reattachment, including the use of
      current bonding techniques, is a restorative treatment option that offers the
      advantages of simplicity, immediate esthetics, and conservatism in cases of
      dental trauma. This article presents a comprehensive literature review on this
      restorative technique. It also provides diagnostic and treatment algorithms to
      simplify and clarify the recommended diagnostic and clinical regimens.

PMID- 9780893
TI  - 6th European Congress on Dental and Maxillofacial Radiology. Oslo, Norway, June 4
      6, 1998. Abstracts.

PMID- 9780894
TI  - Extraoral radiographic imaging of primary caries.
AB  - OBJECTIVE: To evaluate three extra-oral radiographic imaging modalities as
      alternatives to conventional intra-oral film for the detection of primary caries.
      METHODS: Sixty-four extracted primary molar teeth with eighty-five carious
      lesions were radiographed using D-speed film (N = 8), panoramic imaging (N = 8),
      multidirectional tomography (N = 8), and linear tomography (N = 8). Eight trained
      observers were asked to identify the presence or absence of caries on each
      surface using a five point scale. Ground sections were viewed microscopically to
      determine truth. ROC curve areas (Az) were generated from observer responses and
      assessed with ANOVA. RESULTS: Average of Az for the detection of combined results
      for proximal and occlusal lesions were 0.70 for D-speed, film, 0.58 for linear
      tomography, 0.64 for both multidirectional tomography, and panoramic film.
      Turkey's pairwise comparisons of Az revealed that D-speed film was significantly
      better than linear tomography (P = 0.0039). When data were divided into proximal
      and occlusal surfaces the variability due to modality remained significant (P =
      0.0003 and P = 0.0024 respectively). Turkey's comparisons for proximal surfaces
      revealed that D-speed film was significantly better than linear tomography (P =
      0.0007), multidirectional tomography (P = 0.0010) and panoramic radiography (P =
      0.0100). For detection of occlusal lesions, multidirectional tomography was
      significantly better than linear tomography (P = 0.0075) and panoramic
      radiography (P = 0.0034), but not significantly different from D-speed film (P =
      0.2337). CONCLUSIONS: Multidirectional tomography and panoramic radiography
      performed as well as intra-oral D-speed film for the combined assessment of
      proximal and occlusal caries in the model used. when proximal surfaces were
      evaluated alone, D-speed film was significantly better. For occlusal caries there
      was no statistically significant difference between multidirectional tomography
      and D-speed film.

PMID- 9780895
TI  - Adverse reactions to nonionic iodine in contrast-enhanced computed tomography:
      usefulness of monitoring vital signs.
AB  - OBJECTIVE: To report on adverse reactions to intravenous nonionic iodine contrast
      media and evaluate the usefulness of monitoring vital signs. MATERIAL AND
      METHODS: A prospective study of 1537 consecutive patients who received contrast
      enhanced CT with nonionic iodine was performed. Systolic and diastolic arterial
      blood pressure, pulse rate and arterial blood oxygen saturation were monitored.
      Severity of adverse reactions was classified as minor, intermediate and severe.
      RESULTS: A total of 64 adverse reactions developed in 57 patients. The overall
      prevalence was 3.7% (57/1537). The most common symptom was nausea (18/64)
      followed by pharyngeal discomfort (11/64). One patient had a severe reaction
      consisting of prolonged hypotension. Four patients had an intermediate reaction,
      three transient hypotension or hypertension and one extensive urticaria and
      facial edema. In two out of four patients who became hypotensive or hypertensive,
      the reactions developed without any obvious clinical symptoms. CONCLUSIONS:
      Severe or life-threatening acute adverse reactions to intravenous nonionic iodine
      contrast media may develop without any obvious clinical symptoms. Monitoring
      vital signs is very helpful for early detection.

PMID- 9780896
TI  - The role of three-dimensional spiral computed tomography in oral metastases.
AB  - We present the spiral 2DCT and 3DCT imaging findings in two patients with oral
      metastases, one with breast and the other with prostate cancer. In order to
      demonstrate the contribution of these techniques in the evaluation and treatment
      planning of such lesions. 3DCT can help to define further the extent of
      osteolytic involvement noted on initial 2DCT images, allowing better localization
      and visualization of the anatomical regions involved. We conclude that 3DCT is a
      useful adjunct for the management of maxillofacial tumors involving bone.

PMID- 9780898
TI  - Computed tomography and magnetic resonance imaging in the management of coronoid
      process hyperplasia: review of five cases.
AB  - OBJECTIVE: To describe the imaging features of primary bilateral coronoid
      hyperplasia, with particular reference to the use of CT and MRI. MATERIALS: A
      series of five cases is reviewed. RESULTS: The correct diagnosis was achieved
      with panoramic radiography alone or with the addition of CT. MRI did not provide
      additional pre-operative information; it was useful in the postoperative
      assessment of poor functional recovery in order to determine the presence of
      haematoma and/or fibrosis. CONCLUSIONS: Although panoramic radiography alone can
      demonstrate this condition, CT has an important role in diagnosis and is useful
      for an adequate surgical planning by allowing assessment of the size of
      impingement of the coronoid processes. MRI is useful for evaluating postoperative
      complications involving soft tissue.

PMID- 9780897
TI  - Radiological features of primary intra-osseous carcinoma of the jaws. Analysis of
      the literature and report of a new case.
AB  - OBJECTIVES: To analyse the clinical and radiological features of primary intra
      osseous carcinoma of the jaws (PIOC). MATERIAL AND METHODS: Twenty-four cases (23
      from the literature and one new case) of PIOC were reviewed. RESULTS: Patient's
      age at time of diagnosis ranged from 4-76 years, (mean 50 years). Male to female
      ratio was 1.7:1. Most lesions (79%) were in the mandible and of these, 95% were
      in the posterior area, approximately 70% of the maxillary lesions were in the
      anterior region and crossed the midline. In 87% of the cases PIOC was
      radiolucent; the remainder were mixed radiolucent-radiopaque lesions. The
      radiological borders were defined but none corticated in 57% of the cases and
      diffuse in 43%. The lesion was unilocular in 61% and not loculated in 35%.
      CONCLUSIONS: The variable radiological features of PIOC and its deceptive
      resemblance to odontogenic cysts and other tumours of the jaws suggests that
      despite its rarity, PIOC should be considered in the differential diagnosis of
      radiolucent lesions in the jaws.

PMID- 9780899
TI  - Radiographic assessment of changes in marginal bone around endosseous implants
      supporting mandibular overdentures.
AB  - OBJECTIVES: To evaluate the reliability of a new method for quantification of
      radiographic changes in the marginal bone around implants. METHODS: Three groups
      of seven patients treated with an overdenture supported by two endosseous
      implants (Brnemark, n = 7 patients; IMZ, n = 7 patients; ITI Bonefit, n = 7
      patients) were selected. Six weeks after loading the implants, radiographs were
      obtained using the long cone technique and an aiming device, scanned and
      digitized. Two observers measured the height and area of the peri-implant bone
      defects twice. The difference between measurements was statistically analysed
      using paired t-tests. RESULTS: There were small differences in interobserver
      error for the Brnemark implant system (P < 0.05), but no significant differences
      for the IMZ and ITI Bonefit. There were no significant difference in
      intraobserver error with any of the three implant systems (P > 0.05).
      CONCLUSIONS: The newly developed technique by measuring the area of the defect
      overcomes some drawbacks of existing techniques for quantification of peri
      implant bone loss in the mandible.

PMID- 9780900
TI  - Low-field magnetic resonance imaging for implant dentistry.
AB  - OBJECTIVE: To evaluate the use of a low-field magnetic resonance scanner for
      assessment of available bone for placement of osseo-integrated dental implants.
      METHODS: Eleven Patients were examined to assess suitability for implant
      placement using a 0.2 tesla 'open' scanner. Imaging/surgical templates were
      constructed, with gadolinium markers to allow accurate location of the implant
      sites. RESULTS: In all cases, localisation of potential implant sites was easily
      made and full information in all three planes readily available. Artefacts were
      few and localised, (noted on one site in one case only). Vital structures (nerves
      and vessels), and the variable geometry of the floor of the maxillary sinus were
      clearly seen, and cortical bone delineated from cancellous. The appearance of
      soft tissues in the scan allowed the surgeon to assess the final profile of the
      patient. CONCLUSION: Low-field magnetic resonance imaging has definite potential
      for pre-implant assessment. Full sectional information is readily available at
      any desired plane with no need for reformatting. The information for accurate and
      safe implant placement is clear. The technique uses no ionising radiation.
      Further work is needed to evaluate spatial distortion caused by magnetic
      susceptibility effects at air/tissue interfaces, but our calculations indicate
      that at low field, using an appropriate protocol, the effect will not be
      substantial.

PMID- 9780902
TI  - Comparison of two methods for radiometric evaluation of resin-based restorative
      materials.
AB  - OBJECTIVES: To compare radiographic densitometry with indirect digital image
      analysis for evaluating the radiopacity of nine different resin-based restorative
      materials. METHODS: Discs of amalgam and nine different resin-based restorative
      material, 10 mm in diameter and 2 mm thick, were radiographed together with 2 mm
      thick discs of intact and carious human teeth and an aluminium stepwedge. Density
      was evaluated by digital transmission densitometry and with the histogram
      function of an image analysis programme (Image Tool 1.27, University of Texas
      Health Sciences Center, Texas, USA) following the digitization of the radiographs
      with a drum scanner. RESULTS: The two methods produced essentially similar
      results. With both methods, Dyract (Dentsply De Trey, Konstanz, Germany) had the
      highest radiodensity and Estilux Hybrid (Kulzer, Werheim, Germany) the lowest.
      CONCLUSION: Digital image analysis is a suitable alternative to transmission
      densitometry for evaluation of the radiopacity of restorative materials.

PMID- 9780901
TI  - An evaluation of digital subtraction radiography for assessment of changes in
      position of the mandibular condyle.
AB  - OBJECTIVE: To compare conventional visual evaluation with digital subtraction for
      assessing changes in condylar position on TMJ radiographs. METHODS: Horizontally
      corrected oblique lateral transcranial radiographs of the TMJ were taken
      bilaterally with and without a stabilisation or a control appliance on the same
      occasion in 20 patients. All of the radiographs were assessed both conventionally
      and following digital subtraction by seven observers. Three observers assessed
      both sets of radiographs twice to calculate observer agreement. RESULTS: There
      were no statistically significant differences in observer performance or
      diagnostic outcome between the two techniques. Intra-observer agreement varied
      between 85 and 90% for the conventional visual evaluation and between 62 and 85%
      for digital subtraction. Although interobserver agreement was greater with the
      conventional evaluation the difference was not significant. CONCLUSION:
      Conventional visual evaluation is recommended for the assessment changes in
      condylar position from TMJ radiographs.

PMID- 9780903
TI  - Effects of calibration and automatic greyscale adjustment on detectability of
      simulated bone lesions using a storage phosphor system.
AB  - OBJECTIVES: To analyse the interaction of calibration, automatic greyscale
      adjustment and X-ray exposure on the evaluation of simulated bone lesions with
      the Digora (Orion Corporation Soredex, Helsinki, Finland) storage phosphor
      system. METHODS: Exposures were made under five conditions based on the exposure
      time for Ektaspeed Plus film: A-calibration exposure 100%, exposure 100%; B
      calibration exposure 100%, exposure 50%; C-calibration exposure 100%, exposure
      10%; D-calibration exposure 50%, exposure 50%; E-calibration exposure 10%,
      exposure 10%. Series of images of artificial bone lesions were created each
      representing one of the five conditions, with or without automatic greyscale
      adjustment and including one of two lesion sizes. The series were evaluated by
      seven expert radiologists. Results were analysed by means of MANOVA statistics.
      RESULTS: The large lesions were evaluated significantly better than the small
      lesions (P < 0.011). The two 10% exposure conditions were evaluated significantly
      worse than the other three (P < 0.029) which had comparable results. Automatic
      greyscale adjustment had no significant effect (P > 0.253). CONCLUSIONS: The
      Digora should be calibrated for the highest exposure to be used to optimize the
      wide latitude. Automatic greyscale adjustment is not useful for the detection of
      simulated bone lesions.

PMID- 9780904
TI  - Comparison of reliability of manual and computer-intensive methods for
      radiodensity measures of alveolar bone loss.
AB  - OBJECTIVE: To compare the reliability of radiodensity measurements made from
      dental radiographs with manual and a novel computer-intensive methods. METHODS:
      As part of a prospective study of postmenopausal women, a series of seven
      vertical bitewing radiographs were taken of 36 patients. One of each set of
      radiographs was repeated. The original and the corresponding duplicate
      radiographs were used in this study. Radiographs were digitized at 50 microns
      spatial resolution and 12-bit gray-scale resolution. For the Manual Method,
      original and duplicate radiographs were manually cropped to improve image
      homology, histogram matched and mean pixel gray-scale values determined for an
      alveolar bone ROI within each image. For the computer-intensive method, images
      were put into registration with ANALYZE software (Mayo Foundation, Rochester,
      MINN, USA), cropped automatically, histogram matched and color-coded on the basis
      of the per cent difference. Alveolar bone ROIs adjacent to clinical crowns and
      root surfaces whose color code indicated less than a 5% change were sampled.
      Method error (ME) and the coefficient of variation of method error (CVME) were
      calculated. RESULTS: With the Manual Method the SD between original and duplicate
      measures was 95.21 out of 4096 gray scale values; ME = 67.32; CVME = 3.78%. For
      the computer-intensive method, the corresponding values were 54.74, 38.71, and
      2.29%. CONCLUSIONS: The new computer-intensive method resulted in a 40%
      improvement over the Manual Method in the precision of radiodensity measurements.

PMID- 9780905
TI  - Radiological features of hereditary opalescent dentin.
AB  - A case of hereditary opalescent dentin is described, which showed the same
      clinical and radiological features as those reported previously. However, there
      was no evidence of osteogenesis imperfecta. While a diagnosis of type II
      dentinogenesis imperfecta was therefore made, this case also had features
      characteristic of type III dentinogenesis imperfecta. Treatment by means of an
      overdenture is described.

PMID- 9780906
TI  - Friends, foes, and secret agents.

PMID- 9780907
TI  - A defect by many other names.

PMID- 9780908
TI  - Bilambdoid and posterior sagittal synostosis: the Mercedes Benz syndrome.
AB  - A consistent pattern of craniosynostosis in the sagittal and bilateral lambdoid
      sutures is described in three patients. The external cranial ridging associated
      with fusion of these sutures produces a characteristic triradiate, or "Mercedes
      Benz," appearance to the posterior skull. Locally marked growth restriction is
      evident in the posterior fossa with compensatory secondary expansion of the
      anterior fossa manifesting a degree of frontal bossing which mimics bicoronal
      synostosis. Although this appearance could lead to inadvertent surgery in the
      frontal region, attention to the occipital region with wide early suture excision
      and vault shaping is indicated.

PMID- 9780909
TI  - The combination of endoscopy and distraction osteogenesis in the development of a
      canine midface advancement model.
AB  - The requirements for reconstruction in patients with midface hypoplasia can be
      formidable: a bicoronal scalp incision, Le Fort III or monobloc skeletal
      advancement, harvesting and insertion of bone grafts, application of rigid (and
      occasionally intermaxillary) fixation, blood transfusions, and prolonged
      operative time and hospitalization. The introduction of the endoscope offers the
      possibility of minimally invasive surgery with improved visualization of the
      osteotomy sites. The development of distraction osteogenesis as a surgical
      technique allows controlled and gradual advancement of the osteotomized skeletal
      segment and associated soft tissue. The purpose of this study was to develop a
      canine model of an endoscopically assisted Le Fort III osteotomy with attendant
      midface distraction. Four mongrels (20 kg in weight) were study subjects. Three 2
      cm skin incisions were made (two perpendicular to the zygomaticomaxillary suture
      and one perpendicular to the nasofrontal suture). The soft tissue and periosteum
      were evaluated bluntly. Retractors specially designed for the project created a
      space for endoscopic visualization. Bilateral zygomatic, nasofrontal, and medial
      orbital wall osteotomies, corticotomies, or both were performed under endoscopic
      visualization using a reciprocating saw; the medial orbital wall sectioning was
      specifically not completed (i.e., corticotomy) to avoid laceration of the mucosa
      and attendant bleeding. The pterygomaxillary osteotomy was completed with an
      osteotome and mallet. Finally, the nasal septum was only partially divided with
      an osteotome to avoid excessive blood loss. Four distraction devices were placed
      across the above-noted osteotomies (two across the nasofrontal osteotomy and one
      across each lateral osteotomy). The animals were distracted 1 mm per day for 16
      to 40 days after surgery (16-40 mm of linear distraction). Cephalograms and
      computed tomography scans were obtained before and after distraction. The animals
      were killed after remaining in fixation for 4 to 6 weeks after distraction. All
      soft tissue was removed and the skull was examined. Photos were obtained
      throughout the experiment for documentation. The study demonstrated that Le Fort
      III osteotomies can be performed successfully via small incisions with endoscopic
      assistance in canine subjects with excellent visualization and minimal bleeding.
      The advancement of the midface segment can be achieved by activation of an
      external distraction device.

PMID- 9780910
TI  - A rare complication of craniofacial fibrous dysplasia.

PMID- 9780911
TI  - Commentary on modification of Playtex nurser for cleft palate patients.

PMID- 9780912
TI  - Commentary on effect of cranial suture autotransplantation from metopic to
      coronal suture.

PMID- 9780913
TI  - Surgical outcomes using bioabsorbable plating systems in pediatric craniofacial
      surgery.
AB  - The purpose of this study was to evaluate the surgical outcomes of the 1.5-mm
      LactoSorb plating system (Walter Lorenz Surgical, Inc., Jacksonville, FL, U.S.A.)
      used to stabilize the osteotomized calvarial bone in pediatric patients who have
      undergone craniofacial surgery. The records of 33 consecutive pediatric patients
      who underwent craniofacial surgery from January 1997 through December 1997 were
      reviewed. There were 18 male and 15 female patients, and the age ranged from 4
      months to 12 years. Patients were followed-up at 1 week, 1 month, 3 months, 6
      months, and 12 months after surgery. For those patients reviewed, the following
      information is included: age, sex, diagnosis, surgical procedures, number and
      size of LactoSorb plates and screws used in each patient, operative difficulty of
      the screws and the heat pack, and postoperative complications, including wound
      healing, palpability, and infection. The LactoSorb plating system was used to
      stabilize the osteotomized calvarial bones in 33 patients who were diagnosed
      with: 1) craniosynostosis, 2) hydrocephalus, 3) fibrous dysplasia, or 4) cranial
      deformation. Orbital rim advancement and anterior cranial vault reshaping were
      performed in 17 patients. Posterior cranial vault reshaping, orbital rim
      advancement, and anterior cranial vault reshaping were performed in eight
      patients. Posterior cranial vault reshaping only was performed in seven patients.
      Excision of fibrous dysplasia from temporal bone was performed in one patient.
      One patient had a postoperative wound infection, and LactoSorb plates were
      palpable postoperatively in four patients. The LactoSorb plating system provided
      adequate rigidity for stabilizing the osteotomized calvarial bone during surgery
      and maintained adequate rigidity after surgery during the bone healing period
      before absorption. This plating system showed satisfactory results in pediatric
      craniofacial surgery patients.

PMID- 9780914
TI  - Reduction in morbidity after iliac crest bone harvesting: the concept of
      preemptive analgesia.
AB  - The technique of autologous iliac crest bone grafting is an important aspect in
      the treatment of patients with cleft lip, cleft palate, and other craniofacial
      disorders. In patients with cleft lip and palate, the alveolar bone graft creates
      a continuous maxillary arch, closes the oronasal fistula, provides bony support
      for facial soft tissue and teeth, and facilitates orthodontic movement of teeth.
      The anatomic and physiologic benefits of this and similar autologous bone graft
      procedures are apparent. However, pain at the donor site represents a significant
      source of postoperative morbidity. This study was conducted to evaluate
      postoperative pain and the ability to perform activities of daily living after
      bupivacaine infiltration to iliac crest donor sites. Thirty-four alveolar bone
      graft patients (18 females, 16 males) treated at two teaching hospitals were
      included in the study. Eleven of the patients received intraoperative bupivacaine
      at the iliac donor site and 23 did not. A questionnaire was returned by all
      participants, and telephone follow-up was obtained. Responses to postoperative
      pain, time period to ambulation, and ability to perform activities of daily
      living were evaluated. Patients who received postoperative bupivacaine
      experienced delayed onset of postoperative pain, earlier ambulation, and were
      able to return to normal daily activity in a shorter period of time than those
      patients who received no local anesthesia. The concept of preemptive analgesia
      and its application to craniofacial surgery is discussed.

PMID- 9780916
TI  - Reuse of tumorous calvarial bone after gamma irradiation.
AB  - Reconstruction of calvarium after tumor resection may present several technical
      difficulties. The authors reused the resected calvarial bone in four patients
      after submitting the bone to a lethal dose of gamma radiation. The authors
      conclude that resected, irradiated, tumorous bone can be reused for the
      reconstruction of its own defect. This provides a simple method of
      reconstruction. Partial bone resorption should be anticipated but further
      reconstruction, if needed, will be facilitated.

PMID- 9780917
TI  - Intraorbital osteoma and surgical strategy.
AB  - The most common tumoral lesion of the bony orbital region is osteoma. It is an
      infrequent and benign tumor, and generally attacks the craniofacial skeleton, but
      intraorbital involvement is extremely rare. After necessary radiologic
      examinations (radiographs and computed tomography scanning), surgery should be
      planned according to the tumor's localization. In the case presented here,
      osteoma originated mainly from the medial orbital wall. Therefore, for better
      surgical exposure, extra- and intracranial approaches were planned and carried
      out. The mass was removed successfully. At the 3-year follow-up, no recurrence
      was shown.

PMID- 9780915
TI  - Intraorbital squamous epithelial cyst: an unusual complication of Silastic
      implantation.
AB  - Thin Silastic sheet alloplasts (Dow Corning, Midland, MI, U.S.A) are commonly
      used to reconstruct posttraumatic orbital floor defects. Complications associated
      with orbital Silastic implantation include infection, migration, and extrusion.
      The authors report an unusual case of an intraorbital, squamous, epithelial-lined
      cyst appearing as progressive vertical globe dystopia and proptosis occurring
      after Silastic reconstruction of a traumatic orbital floor defect.

PMID- 9780918
TI  - Infantile hemangioma of the accessory parotid gland.
AB  - Parotid gland tumors, especially those of the accessory parotid gland, are rare
      in infancy. Although infantile hemangiomas have been frequently reported as a
      cause of parotid gland tumors, their association with the accessory parotid gland
      has not been reported. This article describes the presentation of a hemangioma of
      the accessory parotid gland in an infant. Review of the literature and treatment
      methods are discussed.

PMID- 9780919
TI  - Progressive systemic sclerosis: rare localization of the maxillofacial district.
AB  - The authors focus on a case of scleroderma, or progressive systemic sclerosis.
      Scleroderma is a disease of unknown cause, characterized by an abnormal synthesis
      of connective tissues that causes a sclerosis of the skin involving organs and
      systems at various levels. It may appear in different forms and may involve,
      although not frequently, the maxillofacial district. The authors examined a 21
      year-old woman who had been diagnosed with systemic progressive sclerosis in
      1994. The patient showed a strong limitation of oral aperture, evidenced by an
      electrognathographic test, and osseous changes. Panoramic and full-mouth
      intraoral radiographs showed a complete agenesis of coronoid processes on both
      sides, whereas the angles and the rising branches of the mandibular and
      periodontal ligaments appeared normal. The patient was diagnosed as having
      maxillofacial localization of scleroderma with involvement of coronoid processes
      bilaterally.

PMID- 9780920
TI  - Japanese sisters with Pfeiffer syndrome and achondroplasia: a mutation analysis.
AB  - The authors report the rare existence of a family that includes an older sister
      with Pfeiffer syndrome and a younger sister with achondroplasia. Gene analysis of
      these patients showed a T341P mutation in the FGFR2 gene in the patient with
      Pfeiffer syndrome, and a G380R mutation in the FGFR3 gene in the patient with
      achondroplasia. Both mutations have been reported previously. Their parents had
      no mutation in either locus. This result suggests the possibility that there may
      be predisposing factors for different FGFR mutations.

PMID- 9780922
TI  - New advances in craniofacial surgery.

PMID- 9780923
TI  - Craniofacial surgeons and research.

PMID- 9780921
TI  - Modified Le Fort III osteotomy in adult Crouzon disease.
AB  - The authors present a unique case of a woman with Crouzon disease who was treated
      for symptomatic exorbitism with a modified Le Fort III osteotomy. Midface
      advancement with reduction of exorbitism was accomplished without intermaxillary
      fixation. The technical details are described.

PMID- 9780924
TI  - Importance of the critical-size bone defect in testing bone-regenerating
      materials.
AB  - A substantial interest exists in developing substitute materials and human
      recombinant bone-inducing factors to enhance bone regeneration both in the
      craniofacial complex and in other parts of the skeleton. A persistent problem has
      been to find an animal model that allows for the comparison of different
      osteopromotive materials. The purpose of this investigation was 1) to determine
      whether a 5-mm calvarial defect in adult rats fulfilled the requirements of a
      critical-size bone defect and 2) to discuss the use of this animal model in
      assessing bone repair in the craniofacial region. Bilateral full-thickness
      calvarial defects were trephined in the calvarial bone of 56 5- to 6-month-old
      Wistar rats. Except for minor amounts of bone formation limited to the margins of
      the defect, none of the defects revealed any signs of spontaneous bone
      regeneration 6 and 12 months after surgery. The full-thickness 5-mm calvarial
      defects thus fulfill the criteria for a critical-size bone defect. This animal
      model allows for an experiment with a paired design, it avoids inclusion of the
      sagittal suture in the osseous defect, and it thereby minimizes morbidity by
      reducing the risk of damaging the midsagittal sinus. An adequate experimental
      model has been developed to evaluate the efficiency of osteopromotive materials
      in the healing of bone defects in the craniomaxillofacial region.

PMID- 9780925
TI  - Use of a resorbable fixation technique for maxillary fractures.
AB  - The use of nonmetallic rigid fixation (plate and screws) composed of resorbable
      polymers (poly L-lactic acid and polyglycolic acid) for the repair of isolated
      maxillary (LeFort I) fractures was studied in 11 patients. Provided good bone
      (noncomminuted) was available for fixation placement, no differences were
      observed in intraoperative maxillary stability or long-term postoperative
      results.

PMID- 9780926
TI  - Controlled multiplanar distraction of the mandible: device development and
      clinical application.
AB  - Distraction osteogenesis has been shown to be an effective method of lengthening
      and augmenting endochondral bone. It has also been applied effectively in the
      reconstruction of the membranous bones of the craniofacial skeleton. With the
      accumulation of clinical experience in mandibular distraction, the differences
      between endochondral and membranous bone distraction have become apparent,
      especially in the limitations of uniplanar distraction for the three-dimensional
      reconstruction of the deficient mandible. Distraction of the mandible in a single
      plane cannot satisfy fully the functional and structural requirements of the
      patient with malocclusion as well as deficiency of the skeletal and soft tissue.
      This study reports the development and clinical use of a multiplanar mandibular
      distraction device with the ability to achieve linear distraction (Z-plane or
      sagittal), angular distraction (Y-plane or vertical), and transverse distraction
      (X-plane or coronal). The device contains two independent gear arrangements
      attached to two arms that extend from the central unit. Therefore, the trajectory
      of the regenerated bone may be changed during the distraction process. The device
      also allows manipulation of the various planes of movement independent of each
      other. Furthermore, the rotational points for the multiplanar distraction devices
      are located at a single point; therefore only a single osteotomy and two pin
      sites are required. The multiplanar distraction device allows the surgeon to
      customize and contour the dimensions of the distraction process by controlling
      the trajectory of the translation of the regenerated bone.

PMID- 9780927
TI  - Pharyngoplasty in patients with cleft lip and palate after maxillary advancement.
AB  - The development of velopharyngeal incompetence and increased hypernasality after
      maxillary advancement has been described previously by several authors. If speech
      and velopharyngeal function deteriorate after maxillary advancement,
      pharyngoplasty is frequently the treatment procedure of choice because of the
      natural cause of the deficit. Of 91 cleft lip and palate patients who have
      undergone maxillary advancement at the Australian Cranio-Facial Unit, 23 patients
      received a pharyngoplasty after surgery. Thirteen of these patients who had pre-
      and postoperative speech evaluations were included in this study. Of the 13
      patients, six patients received a superiorly based pharyngeal flap, two patients
      underwent an orticocheal pharyngoplasty, and five patients received either a
      revision or augmentation of the previous flap based on results of preoperative
      examinations. Serial nasendoscopic evaluations were available for 11 of these 13
      patients, and they demonstrated that velopharyngeal function improved after
      pharyngoplasty in six patients and was unchanged in five patients. Of the 13
      patients, 10 improved and three patients were unchanged on an intelligibility
      rating. Nine of the 13 patients demonstrated decreased hypernasality and four
      patients were unchanged. Hyponasality decreased in two patients increased in one
      patient, and was unchanged in one patient. Because the results obtained are
      considered acceptable, the authors conclude that pharyngoplasty can be used
      effectively to treat velopharyngeal dysfunction subsequent to Le Fort I maxillary
      advancement.

PMID- 9780928
TI  - Vertical symphyseal osteotomy.
AB  - For the treatment of mild crossbite with increased bigonial distance, the authors
      performed a vertical symphyseal osteotomy on six patients in the last 3 years.
      Three of these patients had cleft lip deformities and the others had operations
      for orthodontic or aesthetic reasons. After exposing the mandible through the
      buccal mucosal incision, both premolars were extracted with or without
      conventional segmental osteotomy. The two vertical symphyseal osteotomies were
      performed with approximately 1 cm between them, and the central part of the
      mandibular bone was discarded. The bilateral segments of the mandibular body were
      fixed in the midline using titanium miniplates. Satisfactory results were
      obtained with a reduction in the size of the mandibular arch, which produced
      better three-dimensional proportions in the bimaxillary area. No patients had
      temporomandibular joint problems, however postoperative orthodontics were
      essential for this type of operation.

PMID- 9780929
TI  - The microdissection cautery needle versus the cold scalpel in bicoronal
      incisions.
AB  - Craniofacial procedures commonly use scalp incisions to optimize surgical access
      and aesthetic results. Although the use of traditional electrocautery instruments
      on hair-bearing tissue has been limited secondary to the width of resulting
      alopecia, needle-tipped electrocautery devices with decreased energy transmission
      have been developed. This study investigates the cosmetic effect of such
      instruments on scalp incisions. Twelve children undergoing craniosynostotic
      correction via bicoronal incisions were included. One side of the incision was
      completed with the cold scalpel whereas the contralateral portion was effected
      using the Colorado MicroDissection Needle (Colorado Biomedical Inc., Evergreen,
      CO, U.S.A.) according to optimal usage instructions. At the conclusion of the
      study period, precise measurements of the resultant width of alopecia were
      obtained from the parietal and temporal regions bilaterally, and were analyzed
      statistically. Also, parents completed a questionnaire concerning subjective
      observations of the surgical incision and its healing. The portions of the
      incision completed with the Colorado MicroDissection Needle demonstrated a wider
      area of peri-incisional alopecia (5.8 +/- 1.8 mm) than that produced by the cold
      scalpel (3.5 +/- 0.87 mm). Not only was this increased width significant
      statistically (P < 0.05), in addition the disparity was noted by the majority of
      parents (10 of 12) either on the patient questionnaire or with nonsuggestive
      verbal questioning. The benefit of the hemostatic incisional technique of
      electrocautery with even needle-tipped instruments must be weighed carefully
      against its cosmetic consequences.

PMID- 9780930
TI  - Average African American three-dimensional computed tomography skull images: the
      potential clinical importance of ethnicity and sex.
AB  - The production of average 'normative' three-dimensional (3D) computed tomography
      surface images of the bony skull has only recently been explored. The authors
      wish to determine the effect of using sex- and ethnicity-specific adult average
      3D skull images for comparisons with patient images at various stages of
      craniofacial surgical management (i.e., diagnosis, treatment planning, prosthetic
      design, image-guided operative procedures, and outcomes assessment). Craniofacial
      surgical reconstruction for abnormal patterns of development, cancer resection,
      or trauma are most likely to benefit from these comparisons. To morphometrically
      test the significance of separating normative 3D skull data by sex and ethnicity,
      the authors collected 52 3D, anatomical landmarks from 3D computed tomography
      scans of dry skulls of 20 Americans of European ethnicity and 20 Americans of
      primarily African (i.e., primarily African and some European) ethnicity. A
      Procrustes-based morphometric analysis of shape detects 1.2 times as much
      interethnic variance as intersex variance. The African American sample presents
      4.2% more dolichocephaly, wider orbits, flatter nasal area, larger gnathic
      anatomy, and more procumbent dentition. Pooling the sexes across both groups, it
      is seen that men tend to have less bulbous crania, more protruding brows, noses,
      and masticatory muscle attachments, and relatively less protrusive palettes and
      anterior mandibles. Despite a small sample size (N = 40), the authors' results
      are statistically significant (P approximately 0.001 overall) for both of the
      main factors, sex and ethnicity, separately.

PMID- 9780931
TI  - Amniotic band facies.
AB  - Craniofacial deformities of 14 patients with amniotic band syndrome at one
      institution were reviewed for morphologic similarities. In addition to associated
      cleft lip and palate, vertical and oblique facial clefts, which were not
      associated with embryologic lines of fusion, were seen. It is hypothesized that
      the prominence of the nasal processes combined with the adjacent stomodeal
      orifice results in utero surfaces, which can lead to free band attachment and
      adherence, resulting in a spectrum of similarly oriented facial defects.

PMID- 9780932
TI  - Median cleft lip with associated midline sinuses.
AB  - Midline upper lip sinuses alone are rare entitities, with less than 25 cases
      reported previously. Midline upper lip sinuses with associated cleft lip are even
      more rare. A patient report of median cleft lip with associated upper lip sinuses
      in a 16-year-old boy is presented. Controversy exists as to whether these
      abnormalities are related. This report demonstrates the plausibility of a cause
      and-effect relationship between midline clefts and sinuses.

PMID- 9780934
TI  - Campus Bio-Medico technique for nasolaryngeal ventilation with reinforced
      laryngeal mask in dental surgery: a patient report.
AB  - The authors report the usefulness of a prototype nasal laryngeal mask airway
      (LMA) used successfully in a disabled 20-year-old woman with severe psychomotor
      retardation and a compromised airway with predictable indexes of impossible
      tracheal intubation in direct laryngoscopy. A 16-ch Foley catheter was inserted
      through the patient's left nostril and guided through her mouth. A size-3
      reinforced LMA was positioned and connected to the distal end of the catheter.
      The LMA-reinforced tube was removed in a retrograde fashion by pulling the
      catheter up with the patient breathing spontaneously. The duration of the entire
      operation was 3 hours 20 minutes, and the patient was able to breathe
      spontaneously and at a 98% saturation average. Nasal reinforced LMA seems to be
      an interesting solution in patients undergoing 1-day dental or maxillofacial
      surgery, but is especially appropriate when nasotracheal intubation is too
      invasive or technically impossible.

PMID- 9780933
TI  - Management of weapon injuries to the craniofacial skeleton.
AB  - One thousand one hundred thirty-five patients suffering from different types of
      facial injuries caused by various weapons were treated in two university
      hospitals in Tehran, Iran from 1984 to 1990. The referred patients suffered from
      one of three types of facial injuries: soft-tissues injuries, 9.16% (N = 104);
      bone fractures, 18.15% (N = 206); and soft-tissue injuries and bone fractures
      (mixed injuries), 72.69% (N = 825). The number of male patients was greater than
      females (1,123 males and 12 females). Anatomically the facial injuries were
      classified into seven groups (lower third; middle third; upper third; lower and
      middle third; lower and upper third; middle and upper third; and lower, middle,
      and upper third). Lower-third facial injuries were the most common injuries,
      72.60% (N = 824); followed by the middle-third injuries, 36.30% (N = 412); and
      the upper-third injuries, 20% (N = 227). The mandible was the most common site of
      injury in the lower-third injuries, zygomatico-orbital fractures were the most
      common site in the middle-third injuries, and the frontal bone was the most
      common site in the upper-third injuries. Of the total number of patients, 3.17%
      were children (N = 36) with different types of maxillofacial injuries. The
      majority of the injuries (52.42%; N = 595) were from bullets. The most common
      injuries not associated with maxillofacial injuries were head and ocular
      injuries. The least common were abdominal injuries. The head injuries were
      classified into five grades according to clinical and computed tomographic
      findings. Treatment of facial injuries ranged from minor repair and/or closed
      reduction to major soft-tissue and/or bone reconstruction. Postinjury
      complications were very high. The follow-up period ranged from 3 months to 3
      years. The aim of this study is to add our experience in the management of facial
      injuries to the literature.

PMID- 9780935
TI  - Facial rehabilitation by the application of osseointegrated craniofacial
      implants.
AB  - A new approach to the facial rehabilitation of patients with congenital and
      acquired deformities is introduced in this short note. This method involves
      having a bone implant that allows the anaplastologist to fabricate a custom
      prosthesis for use in patients with disfigurement. The design of the implantation
      site is done before the surgical procedure. The titanium oxide fixtures and
      abutments are submerged and extrude through the skin by a small window. The
      attachment for the replacement part is achieved by using a metallic bar or
      magnets. A small space is left at the interface for ventilation of the skin and
      to avoid any maceration that will compromise the integrity and long-term accepted
      outcome. This new method is not a replacement of the traditional techniques but
      an augmentation for the accepted methods in facial rehabilitation.

PMID- 9780936
TI  - New approach to the surgical treatment of severe exophthalmos in Graves disease.
AB  - In the last few years, various surgical techniques to correct orbital
      decompression in patients with Graves ophthalmopathy have been proposed. In those
      patients in whom a high degree of exophthalmos is mainly the result of the
      hypertrophied endorbital muscles with respect to endorbital fat hypertrophy,
      lipectomy is insufficient to obtain an acceptable increase of endorbital volume.
      The authors propose a method that provides for the monobloc bilateral
      quadrantotomy by extracranial access. Despite traditional methods of
      decompression, the advantage of this technique is better advancement of the
      orbital margins. The bicoronal and endoral incisions guarantee no facial scars.
      Compared with the craniotomy, the extracranial access is also less stressful for
      the patient.

PMID- 9780937
TI  - Modified channel retractor simplifies sagittal ramus osteotomy procedure.
AB  - A new instrument is described for use in the sagittal ramus split osteotomy by
      Obwegeser. This modified channel retractor simplifies the sagittal ramus
      osteotomy procedure, allows clear vision and easy access, and protects adjacent
      tissues.

PMID- 9780938
TI  - Effect of cranial suture autotransplantation from metopic to coronal suture.
AB  - The aim of this study was to determine the outcome of autotransplanting part of
      the metopic suture to a defect in the coronal suture in a pig model and to
      explore further the concept of functioning and nonfunctioning recipient sites.
      The authors harvested 15-mm x 10-mm bone grafts, incorporating a part of the
      metopic suture, in 10 Yorkshire pigs under general anesthesia. The authors
      immediately autotransplanted the grafts to a surgically created defect along the
      line of the coronal suture. Both donor and graft were either covered with
      pericranium or left bare. Radiopaque titanium markers were inserted to assess
      growth 1) of the transplanted suture; 2) across both coronal sutures; and 3)
      across the metopic suture. Serial radiographs were taken immediately after
      surgery and at 3-week intervals. The pigs were then killed at 21 weeks. The
      cranium was harvested, and blocks of donor site and graft were taken,
      incorporating the embedded titanium markers. Histologic analysis confirmed graft
      take in all pigs. All grafts continued to function as active cranial sutures with
      no growth disturbance compared with the contralateral coronal suture (P = 0.953).
      There was also regeneration of the donor defect, as confirmed by histologic
      analysis, with no growth disturbance across the metopic suture (P = 0.972).
      Pericranium did not alter graft take or subsequent growth (P = 0.964). However,
      pericranium resulted in a much smaller defect (P = 0.045). These results show
      that after autotransplanting a cranial suture to replace another cranial suture,
      the graft continues to grow and function as a cranial suture to meet the
      functional demands of the new recipient site. Pericranium has a significant
      effect on calvarial regeneration but does not affect cranial suture
      autotransplantation.

PMID- 9780939
TI  - Effects of major Class II occlusal corrections on temporomandibular signs and
      symptoms.
AB  - This study explored the relationship between malocclusion and signs and symptoms
      of temporomandibular disorders (TMD) in 124 patients with severe Class II
      malocclusion, before and 2 years after bilateral sagittal split osteotomy (BSSO).
      Patients were evaluated with the Craniomandibular Index (CMI), the Peer
      Assessment Rating Index (PAR Index, to assess gross changes in the occlusion),
      and symptom questionnaires. The results showed a significant improvement in
      occlusion; PAR Index scores dropped from a mean of 18.1 before surgery to a mean
      of 6.1 at 2 years postsurgery (P < 0.001). The CMI and masticatory index (MI) for
      muscle pain indicated clinically small but statistically significant improvement
      (P = 0.0001) from before surgery (mean CMI = 0.14, mean MI = 0.15) to after
      surgery (mean CMI = 0.10, mean MI = 0.08). The number of patients with clicking
      upon opening decreased significantly from 33 (26.6%) to 13 (10.5%) (P = 0.001).
      However, the number of patients with fine crepitus increased from 5 (4.0%) before
      surgery to 16 (12.9%) at 2 years postsurgery (P = 0.005). Significant reductions
      in subjective pain and discomfort were also found 2 years after surgery. The
      magnitude of change in muscular pain was not related to the severity of the
      pretreatment malocclusion, a finding that suggests that factors other than
      malocclusion may be responsible for the change in TMD.

PMID- 9780940
TI  - Clinical examination findings of temporomandibular disorder patients: a factor
      analytic study.
AB  - To assess the latent factor structure of clinical examination findings obtained
      from temporomandibular disorder patients, exploratory factor analysis was used to
      examine the relationships of a large number of variables obtained from a clinical
      examination to a smaller number of latent variables, or factors. Two independent
      samples of patients--an initial sample that consisted of 330 patients who
      complained of facial pain and a validation sample of 161 additional patients-
      were examined to determine whether the factor structure was reliable. A principal
      axis factor analysis with varimax rotation was used for both sets of data. The
      factor structure for the two samples was consistent between the two sets of data.
      Results identified two muscle pain factors (an "intraoral muscle" factor and an
      "extraoral muscle" factor) two unilateral jaw pain factors, and two factors that
      concern joint noise (clicking and crepitus). The implications of these findings
      for the current nosologic systems for temporomandibular disorders are discussed.

PMID- 9780941
TI  - Short-term reproducibility of pressure pain thresholds in masticatory muscles
      measured with a new algometer.
AB  - The purpose of this project was to test the within-day and between-days
      reproducibility of a new and inexpensive algometer. Twelve symptom-free men and
      nine women participated. Pressure pain thresholds (PPTs) of the bilateral
      masseter and temporalis muscles were assessed during four sessions (mornings and
      afternoons of days 1 and 3). During each session, each palpation point of the
      masticatory muscles was measured four times. There was an interval of only a few
      seconds between measurements 1 and 2, and between measurements 3 and 4,
      respectively, while at least 5 minutes of rest were allowed between measurements
      2 and 3. The PPT values between the morning and afternoon sessions and between
      days 1 and 3 were not significantly different. When the within-session
      reproducibility for all muscles was considered, only the PPT values between
      measurements 2 and 4 were not significantly different. Analysis of variance
      showed that the interindividual variability of PPT was 1.4 to 6.8 times higher
      than the variability observed within or between sessions and days. No gender
      difference was found.

PMID- 9780942
TI  - Treatment outcome in patients with craniomandibular disorders of muscular origin:
      a 7-year follow-up.
AB  - The outcome of different treatment modalities after 7 years was investigated in a
      selected group of 50 patients with craniomandibular disorders of muscular origin.
      To minimize the possible effects of selection on the clinical material, the
      selected treatment group was compared to a consecutive group of patients in terms
      of age, gender, intensity/duration of pain, and socioeconomic profile. Both
      groups were comparable in most respects, but the selected group had a longer
      duration and a higher intensity of pain at baseline. There were more men in the
      consecutive group than in the selected group. A combined treatment approach
      resulted in a better outcome than single treatments. Sixty-five percent of all
      patients in the selected group reported improvement at the 7-year follow-up. All
      of the 19 patients who received counseling combined with different occlusal
      treatments improved. Forty-three percent of the patients treated otherwise showed
      improvement. Patients who were aware of stress responded better to treatment.

PMID- 9780943
TI  - The influence of postoperative telephone calls on pain perception: a study of 118
      periodontal surgical procedures.
AB  - This age-matched and sex-matched study examined the influence of postoperative
      telephone calls on pain perception and on the number of analgesics used for pain
      relief. Adult periodontitis subjects (n = 118) received periodontal surgery after
      examination and sanative therapy (scaling, root planing, and removal of local
      irritants). All subjects received similar care, postoperative instructions, and
      medication, except 59 subjects were phoned 24 hours postoperative (PC group), and
      59 were not (NC group). Callers covered 10 points and were reassuring and
      positive about surgical outcomes. One week postoperative, subjects completed a
      questionnaire that rated pain intensity on a visual analogue scale and indicated
      the number of pills used and whether they had been called. Pain and analgesics
      used were significantly decreased in the PC group (P < 0.001) compared to the NC
      group. A significant positive correlation was found between pain and pills used
      in the groups combined (r = 0.79, P < 0.001 PC + NC), and in the groups
      separately (r = 0.50, P < 0.001 PC; r = 0.41, P < 0.01 NC). Postoperative
      communication between healthcare providers and patients significantly reduces
      pain perception and number of analgesics used for relief.

PMID- 9780944
TI  - Are the two heads of the human lateral pterygoid separate muscles? A perspective
      based on their nerve supply.
AB  - Based on biomechanic and electromyographic studies, it has been argued that the
      two heads of the human lateral pterygoid muscle (LPt) are reciprocally active
      during the masticatory cycle. Thus, it has been proposed that the heads be
      considered separate muscles. However, questions about the accuracy of these data
      have arisen. The authors hypothesized that partition cannot be complete without
      an independent nerve supply. To test this, complete unilateral lateral
      pterygoidectomies were performed on 20 dissection room cadavers. A novel
      approach, using an en bloc method, proved optimal to expose the detailed nerve
      supply to the LPt heads. In the two most frequently observed patterns (15 of the
      20 specimens), the heads were supplied from a common source that was derived from
      either the long buccal or mandibular nerve, or from a loop that arose between the
      long buccal and lingual nerves. In a third pattern, independent branches to
      either head arose from the deep temporal, long buccal, or mandibular nerve. In
      only 20% of the specimens did the two heads receive exclusive innervation from
      separate sources. The most significant finding of the present study is that both
      LPt heads in humans are usually supplied by a common proximate source, but each
      head also receives independent nerves in every case. In the absence of precise
      information about the functional components in each nerve branch, these data
      appear to support Juniper's proposal to regard the two LPt heads as entirely
      separate muscles.

PMID- 9780945
TI  - Leeuwenhoek and Vermeer, an association of genius.
AB  - Antony van Leeuwenhoek, the inventor of the microscope and originator of the
      microscopic sciences, had an interesting association with the great Dutch artist,
      Vermeer, whose paintings were recently displayed in major exhibitions in Holland
      and the U.S.A. Leeuwenhoek is of particular interest to dental medicine for the
      first description of the oral bacteria and the first microscopic description of
      the stratified squamous epithelium of the oral mucosa, with its different layers
      from stratum germinativum to stratum corneum.

PMID- 9780946
TI  - Extractions--their risks and rewards.

PMID- 9780948
TI  - Gleanings about dentistry from the world of literature (sixteenth in a series).

PMID- 9780947
TI  - Professional dentistry's road to autonomy.
AB  - Throughout recorded history the dental ills of mankind have been treated by
      medical specialists particularly associated with surgery. However, deep-rooted
      cultural tradition relegated surgeons and those engaged in the dental art to a
      class deemed socially, intellectually and economically inferior to that of the
      physician, causing widespread neglect of dentistry until the 16th century.
      Organizational developments and advances in the technology of medicine and
      surgery during the next two centuries in Europe engendered the emergence of
      dentistry from a virtual trade to a recognized specialty of medicine, setting the
      stage for its phenomenal growth in 19th century America. Perceiving the common
      need, far-seeing and dedicated representatives of dentistry organized, collected
      available literature, instituted an unprecedented system of dental education,
      eliminated the untutored and untrained practitioner, and left the heritage of an
      independent and honored self-governing health care profession.

PMID- 9780949
TI  - Dental remedies in early American husbandry books.

PMID- 9780950
TI  - Dental filling materials in the Confederacy.
AB  - The mid-1800s were innovative and volatile times, both in the development of the
      United States and in dentistry. The political and social manifestation of this
      unrest was the Civil War. The strides in the country's dentistry are indicated by
      the founding of the first dental college, the first dental journal, and the first
      dental society during the two decades before the war.

PMID- 9780951
TI  - Patient bites dentist: an 1894 case report.
AB  - Although dog bites man is a common occurrence, and patient bites dentist not
      unusual, death subsequent to a human bite was most bizarre even for the
      nineteenth century.

PMID- 9780952
TI  - Museu Salles Cunha.

PMID- 9780954
TI  - FDI in Korea.

PMID- 9780953
TI  - The coming of age of the Delta Dental Plan of Massachusetts, 1966-1996.
AB  - In the early nineteen fifties prepaid dental health insurance came of age on the
      West Coast. Because of the hard work of members of the Massachusetts Dental
      Society, dental insurance became available in Massachusetts in 1966. During the
      early eighties the Massachusetts Dental Service Corporation completed its
      separation from the dental society, and in 1985 achieved its independence from
      their management company, Blue Cross. This paper highlights the creative growth
      strategies of the start up company, Delta Dental of Massachusetts, that over the
      past decade has become the number one dental insurance group statewide.

PMID- 9780955
TI  - The Civil War: three dentists who made a difference.

PMID- 9780956
TI  - William Hoffman Gardiner Logan.
AB  - William Hoffman Gardiner Logan, 1872-1943, was one of the outstanding dentists of
      his time. He was president of every major dental organization of his time, was
      instrumental in achieving an independent Army Dental Corps during World War I,
      wrote prolifically, taught at the Chicago College of Dental Surgery (CCDS),
      became Dean, affiliated the school with Loyola University, and engaged in the
      private practice of general dentistry, and later, oral surgery.

PMID- 9780957
TI  - 49th Congress of the Nordic Orthopedic Federation. Copenhagen, Denmark, June 3-6,
      1998. Abstract.

PMID- 9780958
TI  - 51st Annual meeting of the Canadian Cardiovascular Society. Ottawa, Ontario,
      Canada. October 20-24, 1998. Abstracts.

PMID- 9780959
TI  - How many doctors are enough?

PMID- 9780961
TI  - Caring for an aging population.

PMID- 9780960
TI  - Caring for an aging population.

PMID- 9780962
TI  - Caring for an aging population.

PMID- 9780963
TI  - Health care needs versus health care wants.

PMID- 9780964
TI  - Psychological outcomes following maternal serum screening: a cohort study.
AB  - BACKGROUND: Maternal serum screening is used to assist in the prenatal detection
      of congenital anomalies. Its use is controversial, and one concern that has been
      expressed is its psychological effects on women. The authors examined whether
      this test leads to an increase in anxiety and depression among women who have a
      false-positive result as compared with those who have a true-negative result or
      do not undergo testing. METHODS: A prospective cohort study with baseline
      assessment at 15 to 18 weeks' gestation and follow-up at 24 weeks' gestation was
      conducted. Pregnant women at 8 geographically diverse sites across Ontario were
      recruited. The main outcome measures were the state portion of the State--Trait
      Anxiety Inventory and the Center for Epidemiologic Studies Depression Scale.
      RESULTS: Of the 2418 potential subjects 2020 (83.5%) were enrolled and eligible;
      1741 (86.2%) completed the follow-up. A total of 1177 women (67.6%) underwent
      maternal serum screening. No overall adverse psychological effects as a result of
      testing were found at 24 weeks' gestation. Women with a false-positive result had
      a mean increase in anxiety score of 1.6 (95% confidence interval [CI] -1.7 to
      4.9), whereas women with a true-negative result had a mean decrease of 1.1 (95%
      CI -1.8 to -0.3) and those not tested had a mean decrease of 0.4 (95% CI -1.3 to
      0.5). The mean depression score increased by 0.5 (95% CI -0.9 to 2.0) in the
      false-positive group, was unchanged (95% CI -0.3 to 0.4) in the true-negative
      group and increased by 0.2 (95% CI -1.7 to 1.2) in the not tested group. Of the
      women who underwent testing, 87 (7.6%) were unsure of their result at the time of
      follow-up. INTERPRETATION: The results suggest that maternal screening in Ontario
      is not causing serious psychological harm to women. Communication regarding test
      results could be improved, since a substantial proportion of women were unsure of
      their test result.

PMID- 9780965
TI  - Prevalence of potentially reversible dementias and actual reversibility in a
      memory clinic cohort.
AB  - BACKGROUND: Although clinics for the evaluation of cognitive dysfunction have
      typically emphasized the detection and treatment of the reversible causes of
      dementia, it remains unclear whether the treatment of such causes results in
      reversal of the dementia. Therefore, the appropriate work-up for dementia is in
      dispute. METHODS: A chart review was performed with records from an urban
      tertiary care referral-based memory clinic. The records for 196 patients with
      dementia or suspected dementia, seen between October 1991 and December 1993, were
      examined to determine the prevalence of potentially reversible dementias and
      whether the cognitive dysfunction improved or resolved after treatment. Data
      abstracted from the medical charts included demographic information, medication
      use, presence of depression, and results of neuropsychological tests, blood work
      and neuroimaging. The clinical diagnosis, the response to treatment, if
      applicable, and the outcome (mean follow-up period 16 months) were analysed. The
      recommendations of the 1989 Canadian Consensus Conference on the Assessment of
      Dementia (CCCAD) on the use of CT were retrospectively applied in each case.
      RESULTS: Of the 196 patients, 45 (23.0%) had a potentially reversible condition
      identified by history, physical examination, blood testing or CT; in only 7 (3.6%
      of the total) did treatment result in improvement or resolution of the dementia.
      These 7 patients had higher results for the Mini-Mental State examination (mean
      result 26) and exhibited only mild cognitive deficits. Potentially reversible
      lesions were found in the CT scans of 6 (3.1%) patients: 4 had normal-pressure
      hydrocephalus and 2 had a brain tumour. If the CCCAD recommendations had been
      followed, CT would have been performed in 76 (38.8%) of the patients, and 1 of
      the 6 patients with a lesion would have been missed. INTERPRETATION: Both
      potential and actual reversibility of dementia was low in these memory clinic
      patients. The patients whose condition improved with intervention had early and
      milder cognitive deficits, which suggests that thorough evaluation of early
      memory loss is warranted.

PMID- 9780966
TI  - Maternal nutrition, pregnancy outcome and public health policy.

PMID- 9780967
TI  - New variant Creutzfeldt-Jakob disease and the blood supply: is it time to face
      the music?

PMID- 9780968
TI  - Is Canada falling behind international standards for stroke care?

PMID- 9780969
TI  - Using the ALPHA form in practice to assess antenatal psychosocial health.
      Antenatal Psychosocial Health Assessment.
AB  - BACKGROUND: The assessment of the psychosocial health of pregnant women and their
      families, although recommended, is not carried out by most practitioners. One
      reason is the lack of a practical and evidence-based tool. In response, a
      multidisciplinary group created the Antenatal Psychosocial Health Assessment
      (ALPHA) form. This article describes the development of this tool and experience
      with it in an initial field trial. METHODS: A systematic literature review
      revealed 15 antenatal psychosocial risk factors associated with poor postpartum
      family outcomes of woman abuse, child abuse, postpartum depression,
      marital/couple dysfunction and increased physical illness. The ALPHA form,
      incorporating these risk factors, was developed and refined through several focus
      groups. It was then used by 5 obstetricians, 10 family physicians, 7 midwives and
      4 antenatal clinic nurses in various urban, rural and culturally diverse
      locations across Ontario. After 3 months, these health care providers met in
      focus groups to discuss their experiences. A sample of pregnant women assessed
      using the ALPHA form were interviewed about their experience as well. Results
      were analysed according to qualitative methods. RESULTS: The final version of the
      ALPHA form grouped the 15 risk factors into 4 categories--family factors,
      maternal factors, substance abuse and family violence--with suggested questions
      for each area of enquiry. The health care providers uniformly reported that the
      form helped them to uncover new and often surprising information, even when the
      women were well known to them. Incorporating the form into practice was usually
      accomplished after a period of familiarization. Most of the providers said the
      form was useful and would continue to use it if it became part of standard care.
      The pregnant women in the sample said they valued the enquiry and felt
      comfortable with the process, unless there were large cultural barriers.
      INTERPRETATION: The ALPHA form appears to be an important tool in assessing
      psychosocial health in pregnancy and to be readily integrated into practice. More
      study is required to quantify the number of risks identified and resources used,
      to determine the form's reliability and validity and, ultimately, to assess the
      effect of its use on postpartum outcomes.

PMID- 9780970
TI  - Prostate cancer: 2. Natural history.

PMID- 9780972
TI  - Time's running out as physicians await Y2K fallout.
AB  - Canada's hospitals are slowly coming to grips with the millennium bug, but Anita
      Elash reports that no one really knows what impact the move into the year 2000
      will have on computers and medical devices, either in the hospital or doctor's
      office.

PMID- 9780971
TI  - The return of the 100-day cough: resurgence of pertussis in the 1990s.

PMID- 9780973
TI  - Financial troubles abound for new US medical grads.
AB  - Milan Korcok reports on the financial problems facing medical students in the US,
      who often face staggering debt loads upon graduation.

PMID- 9780975
TI  - XIII International Congress of Eye Research. Paris, France, July 26-31, 1998.
      Abstracts.

PMID- 9780977
TI  - Presidential address: a clash of cultures--personal autonomy versus corporate
      bondage.

PMID- 9780974
TI  - Newfoundland angers its MDs by seeking medical help from armed forces.
AB  - When the Newfoundland government announced in June that it would use military
      doctors as a stopgap measure to solve physician shortages in rural parts of the
      province, local doctors weren't impressed. "They thought it was a joke," said Dr.
      Alan McComiskey. They have since learned that it wasn't.

PMID- 9780976
TI  - XVII International Complement Workshop. Rhodes, Greece, October 11-16, 1998.
      Abstracts.

PMID- 9780978
TI  - Living unrelated renal donation: the University of Wisconsin experience.
AB  - BACKGROUND: Living unrelated renal donation (LURD) has the potential to reduce
      the current waiting list significantly for kidney transplantation. The purpose of
      this study was to examine the long-term results of 150 LURDs performed at our
      center during a 16-year period. METHODS: From Dec 23, 1981, to Feb 13, 1998, 150
      LURDs, 219 human leukocyte antigen (HLA)-identical, 577 haploidentical, and 1789
      cadaveric kidney transplant procedures were performed. Surgical complications,
      rejection episodes, infectious complications, and the cause of graft loss and
      death were examined. Ten-year patient and graft survival rates between groups
      were compared. RESULTS: Fourteen surgical complications including lymphocele (n =
      7), ureteral stricture (n = 4), and ureteral leak (n = 3) were seen. Seventy
      eight patients (52%) had 123 rejection episodes and 66 patients (44%) had 1 or
      more infections. Thirty-six allografts were lost and 25 deaths occurred. Patient
      survival rates at 10 years for HLA-identical, haploidentical, LURD, and cadaveric
      transplant procedures were 86%, 82%, 63%, and 64%, respectively. Allograft
      survival rates at 10 years for HLA-identical, haploidentical, LURD, and cadaver
      transplant procedures were 75%, 59%, 56%, and 44%, respectively. CONCLUSIONS:
      Long-term LURD allograft survival rates are lower than those for HLA-identical
      but equivalent to those of haploidentical and better than those of cadaveric
      kidney transplantations. Spousal and nonspousal LURDs should be actively
      encouraged to help alleviate the current donor kidney shortage.

PMID- 9780979
TI  - Total mesorectal excision is not necessary for cancers of the upper rectum.
AB  - BACKGROUND: The technical aspects of surgery of the upper rectum (10 to 15 cm
      from the anal verge) and sigmoid colon are similar, but a change in technique is
      required for surgery of the lower rectum (< 10 cm). The aim of this study was to
      compare the outcomes of the treatment of upper rectal cancer (UR), in which total
      mesorectal excision (TME) was not performed, with outcomes of sigmoid colon
      cancers (S) and lower rectal cancers (LR). METHODS: Between 1980 and 1990, 891
      patients were treated with curative intent for sigmoid (n = 225) and rectal
      cancer (UR = 229; LR = 437). The Kaplan-Meier and Cox proportional hazards
      analyses were used to compare outcomes. RESULTS: The risk of local recurrence
      alone, local and distant recurrence, death as a result of cancer, or any
      recurrence or death as a result of cancer was 3.5, 2.7, 2.1, and 1.9 times higher
      for patients with LR than for patients with UR, but the risk was not increased
      for UR relative to S. CONCLUSIONS: The outcome of treatment for UR is the same as
      for S and differs favorably from that for LR. UR should be treated by the same
      technique as S.

PMID- 9780980
TI  - Perforated appendicitis in children: risk factors for the development of
      complications.
AB  - BACKGROUND: Many aspects of the management of perforated appendicitis in children
      remain controversial. The objective of this study was to define risk factors
      associated with the development of postoperative complications in children
      undergoing treatment for perforated appendicitis. METHODS: We reviewed all
      children (age < 16 years) who were treated for perforated appendicitis at
      Cardinal Glennon Children's Hospital between 1988 and 1997. Inclusion criteria
      included either gross or microscopic evidence of appendiceal perforation.
      RESULTS: Of 285 children with perforated appendicitis, 279 underwent immediate
      operative treatment. Mean patient age was 7.7 years and there were no deaths.
      Major postoperative complications included intra-abdominal abscess (n = 17),
      ileus (n = 7), mechanical intestinal obstruction (n = 6), and wound infection (n
      = 4). All children who had a postoperative abscess had more than 5 days of
      symptoms before operation. Within this subgroup, drain placement was associated
      with not only decreased postoperative abscess formation and but also shorter
      duration of fever and length of hospitalization. The incidence of mechanical
      obstruction or ileus was not increased and the rate of wound infection was
      actually lower after drainage. CONCLUSIONS: Drain placement appears to be helpful
      in children with late diagnosis but is of little benefit when the duration of
      symptoms is less than 5 days. Thus it is likely that drains are most useful in
      patients with well-established and localized abscess cavities.

PMID- 9780981
TI  - Contemporary treatment strategies for external pancreatic fistulas.
AB  - BACKGROUND: Optimal treatment strategies for patients with external pancreatic
      fistulas have evolved with improved radiographic imaging and the development of
      transpapillary pancreatic duct stents. The aim of this study was to examine
      factors affecting fistula closure and develop a classification scheme to guide
      therapeutic interventions. METHODS: Retrospective chart review was made of all
      patients with external pancreatic fistulas treated at our institution from
      January 1991 to January 1997. Side (partial) fistulas maintained continuity with
      the gastrointestinal tract; end (complete) fistulas had no continuity with the
      gastrointestinal tract. RESULTS: Postoperative side fistulas resolved with
      medical treatment in 13 (86%) of 15 patients after a mean of 11 weeks of
      conservative management. Inflammatory side fistulas resolved with medical
      treatment in only 8 (53%) of 15 patients after a mean of 22 weeks; those that did
      not close initially did so with transpapillary stenting. End pancreatic fistulas
      never closed with medical treatment and were unable to be stented; therefore
      internal drainage or pancreatic resection was necessary to achieve closure. There
      were no differences in sepsis rates, Acute Physiology and Chronic Health
      Evaluation II scores, fistula site, total parenteral nutrition, somatostatin
      treatment, or initial fistula output between groups. CONCLUSIONS: Classifying
      external pancreatic fistulas as to their pancreatic duct relationship and cause
      provides important prognostic and therapeutic information.

PMID- 9780982
TI  - The evaluation of breast masses in women younger than forty years of age.
AB  - BACKGROUND: Breast masses in young women are common, but carcinoma is rare. This
      study was undertaken to determine how often a complaint of mass was found to
      represent a dominant mass and to define the role of breast imaging and fine
      needle aspiration cytology (FNA) in the evaluation of clinically nonworrisome
      masses. METHODS: A retrospective review was made of 605 patients younger than 40
      years of age with a breast mass between February 1994 and February 1996. RESULTS:
      Dominant masses were confirmed by surgeon examination in 36% of 484 self-detected
      masses compared with 29% of physician-detected masses (difference not
      significant). With pathologic confirmation, 29% of self-detected masses had a
      dominant mass compared with 19% of physician-detected masses (P = .02). Carcinoma
      was present in 5% of both groups and not predicted by family history. Imaging
      studies were not useful in patients with normal examinations but were more likely
      to identify dominant masses in patients with an examination described as benign
      (P < .001). FNA did not identify any cancers in normal or benign examinations.
      CONCLUSIONS: Self-examination is as reliable as a general physician examination
      in detecting breast masses. When an examination by an experienced surgeon is
      normal, imaging studies and FNA are low yield. When the examination is equivocal,
      directed ultrasonography is a useful adjunct.

PMID- 9780983
TI  - Effect of hypertonic saline solution and dextran on ventricular blood flow and
      heart-lung interaction after hemorrhagic shock.
AB  - BACKGROUND: Hypertonic saline solutions may have beneficial hemodynamic effects
      in the resuscitation of hemorrhagic shock. The effects on cardiac function and
      potential interaction with lung function are controversial and served as the
      basis for this study. METHODS: Domestic swine were resuscitated from hemorrhagic
      shock with equivalent sodium loads of lactated Ringer's solution (LR) or 7.5%
      NaCl plus 10% dextran (HSD). Hemodynamic data were obtained at baseline, shock,
      and after resuscitation. Right ventricular ejection fraction and left ventricular
      change in pressure with respect to time (dP/dt) were used to index contractility.
      Regional myocardial blood flow was determined with microspheres. Lung water was
      determined gravimetrically. RESULTS: There were no differences in the ability to
      restore hemodynamic parameters with equivalent sodium loads of LR and HSD
      resuscitation. Right ventricular ejection fraction and left ventricular change in
      pressure with respect to time were only transiently affected by shock and
      resuscitation. Regional myocardial blood flow was increased above baseline values
      after HSD. The total resuscitation volumes were 1958 +/- 750 mL and 140 +/- 31 mL
      with LR and HSD, respectively. CONCLUSIONS: Although LR and HSD were equally
      effective in the early resuscitation of hemorrhagic shock, this occurred at the
      expense of significantly greater volume requirements for resuscitation with LR.
      This may contribute to cardiac dysfunction in this setting. Enhanced regional
      myocardial blood flow after HSD resuscitation may be beneficial against ongoing
      myocardial stress.

PMID- 9780984
TI  - A study of 362 consecutive laparoscopic Nissen fundoplications.
AB  - BACKGROUND: Open Nissen fundoplication has been shown to be a very effective
      operation in the treatment of intractable gastroesophageal reflux. Because of its
      technical rather than amputative nature, this procedure offers itself to a
      completely laparoscopic approach. Several studies have shown the feasibility;
      however, very few have dealt with the effectiveness of the laparoscopic approach.
      METHODS: Results of laparoscopic Nissen fundoplications performed during a 6-year
      period were reviewed including duration of operation, number of hospital days,
      number of conversions to open procedures, complications, and symptoms. All 362
      patients had evidence of gastroesophageal reflux disease documented by
      radiographic, endoscopic, or pH monitoring testing before the operation. Patients
      with dysphagia or odynophagia underwent manometric evaluation before operation.
      Postoperative evaluation included esophagography and endoscopy at 2 to 3 months
      with an esophagogram yearly thereafter. Follow-up time was 6 months to 6 years.
      RESULTS: The mean time of operation decreased from 2.7 +/- 0.4 hours during the
      period from 1991 to 1994 to 1.8 +/- 0.3 hours from 1994 to 1997. During those
      same periods, the number of days of hospitalization decreased from 2.2 days to a
      mean of 1.5 days. Manometric studies done before the operation (n = 58) showed a
      pressure of 4 +/- 1.2 mm Hg compared with postoperative values (n = 39) of 14 +/-
      1.8 mm Hg. The conversion rate was 0.8% (n = 3), and the complication rate of
      1.9% (n = 7) included the 3 conversions, 2 pneumothoraces, 1 patient with
      postoperative bleeding, and 1 patient with a large abdominal wall hematoma. There
      were 5 failures of the procedure (1.2%). Thirteen patients (3.6%) described
      postoperative symptoms that persisted beyond 2 months, including bloating,
      flatulence, dysphagia, and diarrhea. CONCLUSIONS: With strict selection criteria
      and increasing experience and standardization of technique, laparoscopic Nissen
      fundoplication can provide both safe and effective results for patients with
      chronic symptoms of gastroesophageal reflux disease.

PMID- 9780985
TI  - Refined use of scintigraphy in the evaluation of nodular thyroid disease.
AB  - BACKGROUND: Scintigraphy has been advocated in patients with a thyroid nodule
      when fine needle aspiration biopsy (FNAB) is not definitive. The purpose of this
      study was to determine the incidence of hyperfunctioning nodules in patients
      without a definitive FNAB, the correlation of serum thyrotropin (TSH) levels with
      the functional status of a nodule, and whether a sensitive TSH assay can be used
      in lieu of scintigraphy. METHODS: From 1990 to 1996, patients with a thyroid
      nodule were evaluated with FNAB and serum TSH measurement. Iodine-123
      scintigraphy was reserved for patients without a definitive FNAB and was
      correlated with TSH levels. RESULTS: Of 356 patients with a thyroid nodule, 102
      did not have a definitive FNAB. A hyperfunctioning nodule was diagnosed in 14 of
      the 102 patients. A low TSH level was detected in 12 (86%) of 14 patients with a
      hyperfunctioning nodule (mean = 0.04 +/- 0.38 microIU/mL) and only 20 (23%) of 88
      patients with a hypofunctioning nodule (mean = 0.87 +/- 4.11 microIU/mL) (P <
      .05). Only 2 of 70 (2.8%) patients with a normal or increased TSH level had a
      hyperfunctioning nodule. CONCLUSIONS: A 14% incidence of hyperfunctioning nodules
      in patients without a definitive FNAB warrants the use of scintigraphy but only
      when serum TSH levels are low, thus avoiding unnecessary scans in 91% of patients
      with a thyroid nodule.

PMID- 9780986
TI  - Molecular metastases in stage I pancreatic cancer: improved survival with
      adjuvant chemoradiation.
AB  - BACKGROUND: Reports of improved survival rates for patients with resected
      adenocarcinoma of the pancreas coincide with the adoption of adjuvant
      chemoradiation protocols. The impact of nodal micrometastases demonstrated by
      molecular assays and adjuvant therapy on survival of patients with stage I
      pancreatic cancer has not been adequately assessed. METHODS: A retrospective
      analysis of postoperative chemoradiation on survival in 61 patients undergoing
      resection of pancreatic adenocarcinomas from 1984 to 1997 was performed. Archival
      tumors and regional nodes from 25 patients with stage I cancers were tested for a
      Kiras oncogene mutation using polymerase chain reaction and analysis for
      restriction fragment length polymorphisms (PCR/RFLP). RESULTS: Adjuvant
      chemoradiation was associated with improved survival for stage I (P < .01), but
      not stage III, disease. Seventeen (68%) of 25 patients with stage I disease
      tested had evidence of mutant Kiras in one or more regional nodes. Survival did
      not differ for patients with molecular micrometastases. Six of 17 (35%) patients
      with micrometastases received adjuvant chemoradiation and had improved survival
      (P < .05). CONCLUSIONS: The majority of patients with stage I pancreatic cancer
      have PCR/RFLP evidence of lymph node micrometastases. Adjuvant chemoradiation
      improves survival in these patients by treating micrometastases not detected by
      histology. Adjuvant chemoradiation should be used for patients with stage I
      pancreatic cancers.

PMID- 9780987
TI  - A case controlled comparison of open and laparoscopic splenectomy in children.
AB  - BACKGROUND: This case controlled study compares the efficacy, safety, and cost of
      laparoscopic splenectomy (LS) and open splenectomy (OS) for hematologic disorders
      in children. METHODS: The records of 82 consecutive children and adolescents
      undergoing splenectomy for hematologic disorders between August 1994 and
      September 1997 were reviewed retrospectively. RESULTS: Fifty patients underwent
      LS by a lateral approach and 32 underwent OS through a left subcostal incision.
      Mean age was 7.76 years for LS and 6.9 years for OS. Patient weights were
      similar: (LS, mean 30.5 kg; OS, mean 27.6 kg). Hematologic indications included
      hereditary spherocytosis in 43 children (LS 26, OS 17), sickle cell anemia with
      sequestration in 13 (LS 7, OS 6), immune thrombocytopenic purpura in 14 (LS 8, OS
      6), and 12 with other disorders (LS 9, OS 3). Concomitant cholecystectomy was
      performed in 10 of 50 LS and 6 of 32 OS cases. Accessory spleens were identified
      in 8 of 32 (25%) OS and 9 of 50 (18%) LS cases (P = .578). No LS procedures
      required conversion to OS. The mean estimated blood loss was 54.4 mL for LS and
      49.0 mL for OS (P = .233). LS required a longer operative time (115 vs 83
      minutes, P = .002), less need for postoperative intravenous narcotic (51% vs
      100%, P < .0001), lower total narcotic doses (0.239 vs 0.480 mg/kg morphine, P =
      .006), shorter length of hospital stay (1.4 +/- 0.97 vs 2.5 +/- 1.43 days, P =
      .0001), and lower average total hospital charges ($5713 vs $6564) than OS. There
      were no deaths or major complications in either group. CONCLUSIONS: Laparoscopic
      splenectomy is a safe and effective procedure in children with hematologic
      disorders resulting in longer operative times, less narcotic administration,
      shorter length of stay, and lower total hospital charge.

PMID- 9780988
TI  - Tertiary hyperparathyroidism after renal transplantation: surgical strategy.
AB  - BACKGROUND: An analysis of our experience with tertiary hyperparathyroidism (III
      HPT) in renal transplantations between 1981 and 1996 was reviewed to examine a
      variety of laboratory and clinical variables in this population. METHODS: A total
      of 3233 kidney transplantations were performed; 48 patients underwent
      parathyroidectomy for III HPT. Five patients were excluded from analysis due to
      the development of renal dysfunction. The index 43 patients were divided into two
      groups. Group I consisted of 31 patients (72%) with either enlargement of all
      parathyroid glands (n = 26) or 3/4 gland enlargement (n = 5). These patients were
      assumed to have hyperplasia and underwent subtotal parathyroidectomy or total
      parathyroidectomy. Group II consisted of 12 patients (28%) with single (7/12;
      58%) or two-gland enlargement (5/12; 42%). Group II patients underwent resection
      of only the enlarged glands. RESULTS: Laboratory and clinical parameters showed
      no difference between the groups during long-term follow-up. Most patients in
      groups I and II were eucalcemic after parathyroidectomy. However, postoperative
      hypercalcemia and hypocalcemia did occur in group I (mean postoperative calcium:
      group I = 9.29 +/- 0.63 mg/dL; group II = 9.42 +/- 0.58 mg/dL). CONCLUSIONS: Four
      gland parathyroid enlargement is a frequent finding in III HPT, although
      asymmetric enlargement can occur. Histologically, this represents sporadic
      adenomas and asymmetric hyperplasia. Intraoperative findings should dictate
      surgical strategy; with asymmetric enlargement only the enlarged parathyroid
      glands should be resected.

PMID- 9780989
TI  - Ductography for nipple discharge: no replacement for ductal excision.
AB  - BACKGROUND: Current management of nipple discharge depends on clinical history to
      distinguish pathologic from physiologic discharge. We investigated whether
      ductography supplied additional information in the decision for surgery and/or
      the localization of pathologic lesion. METHODS: A retrospective review of
      patients with a presenting complaint of nipple discharge seen at the Lynn Sage
      Breast Center was conducted from January 1995 to June 1996. Medical records,
      pathology, and ductograms were reviewed. RESULTS: Of 91 patients with nipple
      discharge, 49 met the criteria for physiologic discharge and 42 had pathologic
      discharge. Eleven with physiologic discharge had ductograms; none were abnormal.
      Four of 20 preoperative ductograms were normal but showed intraductal papillomas
      at the time of surgery; 6 of 20 (30%) had multiple lesions. Four lesions on
      ductograms did not demonstrate corresponding lesions in the surgical specimen. It
      is uncertain whether this is due to a missed lesion or a false-positive
      ductogram. CONCLUSIONS: Modern ductography does not reliably exclude intraductal
      pathology and is not a substitute for surgery in patients with pathologic
      discharge. Its utility is in identifying multiple lesions or those with lesions
      in the periphery of the breast.

PMID- 9780990
TI  - Decreased blood oxygen diffusion in hypercholesterolemia.
AB  - BACKGROUND: Improvement of angina pectoris symptoms after cholesterol lowering
      has raised questions as to the underlying mechanisms. METHODS: Rabbit experiment:
      We compared arterial blood samples from New Zealand White cholesterol
      supplemented rabbits (n = 6) with nonsupplemented rabbit samples (n = 4) in a
      closed-loop circulation diffusion system. The pH and partial pressures of oxygen
      (pO2) and carbon dioxide (pCO2) were measured continuously. The samples were
      first oxygen (O2) saturated (pO2, 160 mm Hg; pCO2, 4 mm Hg) and then desaturated
      in 100% nitrogen. Cholesterol levels were determined in whole blood, plasma (P
      Chol), red blood cells (RBCs), and RBC membranes. Human experiment: We exposed
      quadruple desaturated venous blood samples (n = 4) with P Chol levels of 87 to
      400 mg/dL in a gas exchanger to capillary gas conditions (pO2, 23 mm Hg; pCO2, 46
      mm Hg). After 15 minutes we performed blood gas analyses and compared our results
      to baseline values. RESULTS: In the rabbit experiment the cholesterol
      supplemented group as compared to the control group showed higher plasma pO2
      levels during the saturation phase and lower plasma pO2 levels during the
      desaturation phase. It also had a markedly increased RBC membrane cholesterol
      content: 121 +/- 3 (standard error of the mean [SEM]) mg/dL versus 22 +/- 1.7
      mg/dL in the control group (P < .05). This barrier to RBC membrane O2 diffusion
      caused delayed O2 entry into the RBCs during saturation, with a higher plasma
      pO2, and delayed O2 release from the RBCs during desaturation, with a lower
      plasma pO2. In the human experiment the P Chol level was inversely correlated
      with the percentage change of O2 content in milliliters of O2 per deciliter of
      blood (P < .05). CONCLUSIONS: Increased RBC membrane cholesterol in
      hypercholesterolemia appears to decrease the transmembrane O2 diffusion rate.

PMID- 9780991
TI  - Eight years' experience with the use of a transcystic common bile duct duodenal
      double-lumen catheter for the treatment of choledocholithiasis.
AB  - BACKGROUND: We have previously reported an alternative technique for treatment of
      choledocholithiasis found at laparoscopic cholecystectomy (LC) that can be
      considered with selected patients. This study was undertaken to update our
      experience with this alternative technique, which makes serial postoperative
      cholangiograms possible and facilitates stone extraction by assuring access to
      the common bile duct so that a guidewire-assisted endoscopic retrograde
      sphincterotomy can be performed. METHODS: In the period between 1989 and 1997,
      prospective data were maintained on 1043 consecutive patients who underwent LC by
      a single surgeon. Fifty-two patients with abnormal cholangiograms were managed
      with a percutaneously placed double-lumen catheter threaded through the cystic
      duct and advanced into the duodenum. RESULTS: Five attempts failed, 3 because of
      failure to pass the catheter and 2 because of catheter dislodgement. Of the 47
      remaining patients, 2 underwent intraoperative endoscopic sphincterotomies using
      this alternative technique and 45 had cholangiograms repeated at 10 to 14 days.
      Twenty-three had negative cholangiograms, thus avoiding further procedures or
      unnecessary sphincterotomies because of spontaneous stone passage or initial
      false-positive cholangiograms. The remaining 22 had positive cholangiograms.
      Eighteen ultimately underwent sphincterotomies with stone extraction using a
      guidewire placed through the catheter. The other 4 had negative cholangiograms
      after serial follow-up, presumably because of spontaneous stone passage.
      CONCLUSIONS: The use of a transcystic double-lumen catheter passed through the
      ampulla of Vater is an effective and safe alternative for the management of
      choledocholithiasis discovered during LC.

PMID- 9780992
TI  - Application of the new classification for cancer of the cardia.
AB  - BACKGROUND: Cancer of the cardia is now topographically classified into three
      types: type I, with the tumor center in the distal esophagus treated with
      subtotal esophagectomy; type II, arising at the gastroesophageal junction and
      treated with distal esophagectomy and either proximal or total gastrectomy; and
      type III, subcardial cancer treated with extended total gastrectomy. Our
      objective was to review the new classifications and compare the outcomes in
      patients grouped and treated according to these classifications. METHODS: Seventy
      four patients with cancer of the cardia--15 with type I, 30 with type II, and 29
      with type III cancer--underwent surgical resection at our institution between
      1992 and 1997. Postoperative complications, UICC stages, and survival (Kaplan
      Meier) were compared. RESULTS: The majority of patients with type I (73%) or type
      II (53%) cancer had stage I or II tumors, but only 27% of patients with type III
      cancer had this tumor stage (P < .05). Overall 30-day mortality was 4% and
      morbidity was 31%. Curative resections were performed in 73% (54 of 74) of the
      patients with 3-year survival rates of 72% (type I), 68% (type II), and 61% (type
      III). CONCLUSION: The recommended therapy for the different types of cancer of
      the cardia results in acceptable morbidity, mortality, and survival rates.

PMID- 9780993
TI  - Prophylactic jejunostomy: a reappraisal.
AB  - BACKGROUND: The effectiveness of enteral feeding in maintaining postoperative
      nutrition has led some investigators to recommend prophylactic jejunostomy at the
      time of any high-risk abdominal operation. A failed procedure in this setting
      weighs heavily on the side of risk without identifiable benefit. METHODS: A
      benefit/risk analysis comparing complication rate, avoidance of parenteral
      nutrition, and discontinuation of jejunostomy feeding was performed in 92
      patients. These patients were judged retrospectively to be undergoing either a
      prophylactic jejunostomy placed at the time of operation for another serious
      condition (group A) or therapeutic jejunostomy alone (group B) during a 3-year
      period (1993 to 1996). Classification as prophylactic or therapeutic was
      determined by the surgeon's preoperative intent. RESULTS: Avoidance of parenteral
      nutritional support, a goal of prophylactic jejunostomy, was not achieved in 39%
      of the patients. Patients in group A had a 5-fold increase in the risk of
      premature discontinuation of enteral feeds when compared with group B (P < .03).
      The complication rate was higher in group A (41%) than in group B (26%). Four
      life-threatening complications occurred in group A; all required reversal of the
      feeding jejunostomy. CONCLUSIONS: This study suggests that the benefit/risk ratio
      of prophylactic jejunostomy is low. This adds weight to the notion that this
      procedure be abandoned in favor of other forms of nutritional support.

PMID- 9780994
TI  - The correlation of ultrasonic carotid plaque morphology and carotid plaque
      hemorrhage: clinical implications.
AB  - BACKGROUND: This study examined the importance of ultrasonic plaque morphology
      and its correlation to the presence of intraplaque hemorrhage and clinical
      implications. METHODS: One hundred fifty-two carotid plaques associated with > or
      = 50% internal carotid artery stenoses in 135 patients who had carotid
      endarterectomies were characterized ultrasonographically into
      irregular/ulcerative, smooth, heterogeneous, homogeneous, or not defined. All
      plaques were examined pathologically for the presence of intraplaque hemorrhage.
      RESULTS: The ultrasonic morphology of the plaques included 63 with surface
      irregularity (41%), 48 smooth (32%), 59 heterogeneous (39%), 52 homogeneous
      (34%), and 41 not defined (27%). Intraplaque hemorrhage was present in 57 of 63
      (90%) irregular plaques and 53 of 59 (90%) heterogeneous plaques, in contrast to
      13 of 48 (27%) smooth plaques and 17 of 52 (33%) homogeneous plaques (P < .001).
      Fifty-three of 63 (84%) irregular plaques and 47 of 59 (80%) heterogeneous
      plaques had transient ischemic attack (TIA)/stroke symptoms, in contrast to 9 of
      48 (19%) for smooth plaques and 15 of 52 (29%) for homogeneous plaques (P <
      .001). CONCLUSIONS: Irregular and/or heterogeneous carotid plaques are more often
      associated with intraplaque hemorrhage and neurologic events. Therefore,
      ultrasonic plaque morphology may be helpful in selecting patients for carotid
      endarterectomy.

PMID- 9780995
TI  - Prognostic value of intraoperative blood flow measurements in vascular access
      surgery.
AB  - BACKGROUND: The purpose of this study was to correlate intraoperative blood flow
      measurements with outcome in vascular access surgery. METHODS: In 303 patients,
      389 vascular access operations were performed. Intraoperative blood flow
      measurements were made immediately following construction of 227 autogenous and
      162 prosthetic arteriovenous fistulas (AVFs) using a handheld flowprobe. Blood
      flow measurements were stratified by demographic variables such as age, race,
      sex, and presence of diabetes and were correlated with primary and secondary
      (assisted) patency. Statistical methods included life-table analysis and Cox
      proportional hazards model. RESULTS: Blood flow increased progressively from
      distal to proximal access sites and was not significantly affected by age, race,
      sex, or presence of diabetes. Autogenous AVFs with flow rates at or below 320
      mL/min and polytetrafluoroethylene (PTFE) grafts with flow rates at or below 400
      mL/min had significantly worse primary and secondary patency rates compared to
      their higher flow counterparts at all sites. Using hazard analysis flow rate was
      the single most important determinant of primary and secondary patency. PTFE
      grafts with flow rates at or below 400 mL/min also required more interventions
      (1.58 per patient-year) and failed sooner (median time, 0.5 +/- 4.7 months) than
      grafts with flow rates above 400 mL/min (1.08 interventions per patient-year; P =
      .03; median time, 1.6 +/- 5.0 months; P = .003). CONCLUSIONS: Intraoperative
      measurements of access blood flow provide objective, reliable data that correlate
      with outcome. Routine use of this technology might lead to more efficient
      management of patients undergoing hemodialysis access surgery.

PMID- 9780997
TI  - A long-term analysis of 620 patients with malignant melanoma at a major referral
      center.
AB  - BACKGROUND: A univariate and multivariate statistical analysis of a single
      surgeon's experience with resectable malignant melanoma during 26 years (November
      1970 to August 1996) was conducted. METHODS: Six hundred twenty consecutive
      patients were registered. Univariate analysis of disease-free survival (DFS) and
      melanoma survival (MS) was calculated by the Kaplan-Meier method and correlated
      to American Joint Committee on Cancer stage, thickness, ulceration, site, lymph
      node involvement, age, sex, type, and excision margins. Linear trends, log-rank
      test, and pairwise comparisons were used to discriminate differences in survival
      curves. A Cox proportional hazards model was used for multivariate analysis and
      determination of relative risk. RESULTS: Univariate analysis of stage, thickness
      (in millimeters), ulceration, lymph node involvement, age, type, and margins of
      excision were predictive of DFS (5 years, 85.7%; 10 years, 82.5%) and MS (5
      years, 92.2%; 10 years, 87.8%) (P < .01). Multivariate analysis revealed
      correlations with thickness, ulceration, and age in predicting DFS (relative risk
      = 2.75, 2.21, and 1.47, respectively) and MS (relative risk = 2.66, 2.47, and
      1.48, respectively). The 5-year MS rate was 73.3% and 93.3% for patients with
      positive and negative lymph nodes, respectively. Of 133 patients who underwent
      lymph node dissection, 28 (21.1%) had nodal metastases. Patients with primary
      melanomas thicker than 4 mm had 50% metastatic involvement of their lymph nodes.
      CONCLUSIONS: Our findings reveal that thickness, ulceration, and age are the most
      important predicting factors in DFS and MS. The data support including ulceration
      and age in modifying American Joint Committee on Cancer staging for melanoma.

PMID- 9780996
TI  - Assessment of the relationship between timing of fixation of the fracture and
      secondary brain injury in patients with multiple trauma.
AB  - BACKGROUND: It has been suggested that early fixation of a fracture is
      deleterious to eventual neurologic outcome. We undertook this study to determine
      whether the timing of fracture fixation is correlated to neurologic outcome.
      METHODS: We retrospectively reviewed patients with severe head and orthopedic
      injuries requiring fracture fixation. Patients were divided into two groups:
      early fracture fixation (< 24 hours after injury) and late fracture fixation (>
      24 hours after injury). RESULTS: One hundred twenty-three patients met entry
      criteria. During fracture fixation, the early group had a significant 2-, 3-, and
      2-fold increase in crystalloid, blood infusion, and blood loss, respectively.
      There was no difference in oxygen saturation and systolic blood pressure or
      episodes of cranial hypertension or hypoperfusion. There was no difference in
      outcomes as measured by in-hospital complications, stay in the intensive care
      unit or hospital, mortality rates, hospital discharge or follow-up Glasgow Coma
      Scores, or long-term orthopedic or neurologic results. CONCLUSIONS: Patients
      undergoing fracture fixation with severe head injury mandate monitoring of
      intracranial pressure and perfusion and tailored fluid resuscitation to meet
      specific organ end points. Integrating end organ perfusion and pressure with
      meticulous fluid status during the definitive repair phase may reduce the
      exposure to secondary brain injury in patients undergoing early fracture
      fixation.

PMID- 9780998
TI  - Surgical management of aberrant sentinel lymph node drainage in cutaneous
      melanoma.
AB  - BACKGROUND: Sentinel lymph node (SLN) mapping by lymphoscintigraphy has changed
      the surgical management of regional lymph node metastases for melanoma. SLNs
      lying outside of traditional nodal basins are now being identified. Our
      hypothesis is that when preoperative lymphoscintigraphy identifies aberrant SLNs,
      these nodes should be excised and, if histologically positive, lymphadenectomy of
      the aberrant nodal basin should be performed. METHODS: Patients with melanomas 1
      mm or larger Breslow thickness and clinical stage N0M0 underwent
      lymphoscintigraphy and excision with SLN biopsy. Preoperative lymphoscintigraphy,
      intraoperative gamma probe, and intraoperative injection of isosulfan blue were
      performed to identify the SLN. Aberrant SLNs were defined as epitrochlear,
      supraclavicular, or popliteal nodes for extremity lesions and intramuscular nodes
      for truncal and head and neck lesions. RESULTS: Thirty-two patients were entered
      into the protocol. Seven (22%) were found to have aberrant nodes. Five of 19
      patients with extremity melanoma had an aberrant SLN; 2 of 13 patients with
      truncal and head and neck melanoma had an aberrant SLN. CONCLUSIONS: This study
      demonstrates that (1) aberrant SLNs are encountered with similar frequency for
      extremity and truncal lesions, (2) biopsy should be performed on aberrant SLNs
      with intraoperative lymph node mapping with the gamma probe and blue dye, and (3)
      lymphadenectomy of the aberrant region should be considered if the aberrant SLN
      is positive.

PMID- 9780999
TI  - Reduced use of resources by early tracheostomy in ventilator-dependent patients
      with blunt trauma.
AB  - BACKGROUND: Early tracheostomy has been advocated for ventilator-dependent
      patients with blunt trauma, but its advantages have not been examined critically.
      METHODS: We retrospectively reviewed our experience with all patients with blunt
      trauma undergoing tracheostomy during the 6-year period from 1990 to 1995.
      Patients undergoing tracheostomy within the first 6 days of hospitalization were
      designated as early recipients (ET) and those undergoing the procedure at 7 or
      more days were defined as late recipients (LT). RESULTS: The entire study group
      consisted of 157 patients. The ET group contained 62 patients and the LT group
      contained 95 patients. No statistical differences were noted between the 2 groups
      with respect to sex distribution, injury severity scores, probability of survival
      scores, or mortality rates. The mean stay in the intensive care unit for the ET
      group was 15 days compared with 29 days for the LT group (P < or = .001). The
      mean total hospital stay for the ET group was 33 days compared with 68 days for
      the LT group (P < or = .001). The mean estimated per-patient hospital charges for
      only room and ventilator care were $36,609 for the ET group compared with $73,714
      for the LT group. CONCLUSIONS: ET in this patient group resulted in significantly
      lowered use of resources with no adverse effect on outcome.

PMID- 9781000
TI  - Biliary sludge formation during enteral nutrition: prevalence and natural
      history.
AB  - BACKGROUND: Total parenteral nutrition is an etiologic factor in the formation of
      biliary sludge. We studied whether enteral nutrition is also a risk factor for
      sludge. METHODS: Fifty patients with a needle catheter jejunostomy (NCJ) placed
      during a major abdominal operation underwent preoperative and weekly
      postoperative ultrasonography until NCJ feedings were discontinued (1 to 6
      weeks). RESULTS: All patients were men. The mean age was 63.2 +/- 1.6 years.
      Fourteen asymptomatic patients (28.0%) had biliary sludge within 2 weeks of
      beginning enteral feedings through a NCJ. Complete ultrasonographic resolution of
      sludge was observed in 13 of the 14 positive patients within 1 to 2 weeks of
      resuming an oral diet. One patient was lost to follow-up after 14 week; a
      positive sonogram had persisted but the patient remained asymptomatic. During the
      period of observation, no other patient had signs of biliary tract disease.
      CONCLUSIONS: (1) Biliary sludge may form in some patients during enteral feeding
      with NCJ. (2) Sludge is cleared by the gallbladder once an oral diet is resumed.
      (3) There appears to be little risk of complications during postoperative enteral
      feeding.

PMID- 9781001
TI  - Staging laparoscopy in the management of intra-abdominal malignancies.
AB  - BACKGROUND: Laparoscopy in the evaluation of intra-abdominal malignancies has
      become a debated issue. Proponents have claimed that it increases resectability
      rates, whereas opponents suggest that many patients require laparotomy regardless
      of the laparoscopic findings. The purpose of this study was to compare outcomes
      in patients undergoing staging laparoscopy versus those who were managed by
      initial exploratory laparotomy. METHODS: The medical records of all patients
      during an 18-month period who underwent surgical evaluation for upper
      gastrointestinal or hepatobiliary malignancies were reviewed. Forty-eight
      patients underwent staging laparoscopy (SL) initially; 80 patients underwent
      initial exploratory laparotomy (EL). Data obtained included type of cancer,
      laparoscopic findings, laparoscopic determination of resectability, laparoscopic
      procedures, open determination of resectability, open procedures, and length of
      stay (LOS). Statistical analysis was done by using Fisher exact test or the Mann
      Whitney U test. RESULTS: The malignancies of 75% of patients were deemed
      resectable by SL. Of these, 77.8% were resected. This compares to 56.3%
      resectability rate in the EL group (P = .025). SL findings in patients with
      unresectable malignancies were carcinomatosis (75%), liver metastasis (33.3%),
      and direct invasion (16.7%). In the 8 false-negative SLs, 75% were unresectable
      as a result of vascular invasion and 25% for other reasons. Findings in the EL
      group whose malignancies were unresectable were carcinomatosis (34.3%), direct
      invasion (22.6%), liver metastasis (42.9%), and vascular invasion only (17.1%).
      Therefore 82.9% of patients in the EL group could have been determined to have
      unresectable malignancy by SL. In the EL group 22.5% of the laparotomies were
      nontherapeutic, whereas 4.2% of patients in the SL group underwent nontherapeutic
      laparotomy. Average LOS for unresectable patients in the SL group was 0.5 days,
      with 75% discharged the same day of operation. This compares to 10.9 days in the
      EL group (P < .00001) and 7.6 days in the nontherapeutic EL group (P < .00001).
      CONCLUSIONS: SL increases the resectability rate, decreases the nontherapeutic
      laparotomy rate, and decreases LOS in patients with unresectable disease. SL is
      poor at detecting unresectability as a result of vascular invasion only, but this
      accounts for less than one-fifth of patients. Laparoscopic sonography and
      palliation may further decrease the need for EL.

PMID- 9781002
TI  - Complement inhibition prevents gut ischemia and endothelial cell dysfunction
      after hemorrhage/resuscitation.
AB  - BACKGROUND: Complement, a nonspecific immune response, is activated during
      hemorrhage/resuscitation (HEM/RES) and is involved in cellular damage. We
      hypothesized that activated complement injures endothelial cells (ETCs) and is
      responsible for intestinal microvascular hypoperfusion after HEM/RES. METHODS:
      Four groups of rats were studied by in vivo videomicroscopy of the intestine:
      SHAM, HEM/RES, HEM/RES + sCR1 (complement inhibitor, 15 mg/kg intravenously given
      before resuscitation), and SHAM + sCR1. Hemorrhage was to 50% of mean arterial
      pressure for 60 minutes followed by resuscitation with shed blood plus an equal
      volume of saline. ETC function was assessed by response to acetylcholine.
      RESULTS: Resuscitation restored central hemodynamics to baseline after
      hemorrhage. After resuscitation, inflow A1 and premucosal A3 arterioles
      progressively constricted (-24% and -29% change from baseline, respectively),
      mucosal blood flow was reduced, and ETC function was impaired. Complement
      inhibition prevented postresuscitation vasoconstriction and gut ischemia. This
      protective effect appeared to involve preservation of ETC function in the A3
      vessels (SHAM 76% of maximal dilation, HEM/RES 61%, HEM/RES + sCR1 74%, P < .05).
      CONCLUSIONS: Complement inhibition preserved ETC function after HEM/RES and
      maintained gut perfusion. Inhibition of complement activation before
      resuscitation may be a useful adjunct in patients experiencing major hemorrhage
      and might prevent the sequelae of gut ischemia.

PMID- 9781003
TI  - The role of fluorodeoxyglucose and positron emission tomography in the evaluation
      of pancreatic disease.
AB  - BACKGROUND: The difficulties involved in the timely and accurate diagnosis of
      pancreatic disease are well known. The usual imaging modalities usually identify
      abnormalities but may not always differentiate malignancy from other condition
      such as scar tissue or chronic inflammation. The purpose of our study was to
      determine if fluorodeoxyglucose positron emission tomography (FDG PET) can
      accurately diagnose pancreatic disease. METHODS: The records of 15 patients
      presenting with pancreatic disease were retrospectively reviewed. The diagnosis
      suspected by imaging modalities was compared with the final tissue diagnosis. Two
      patients were excluded because no tissue was obtained. RESULTS: Adenocarcinoma
      was diagnosed in 9 patients. A mass consistent with this diagnosis was seen in 8
      of 9, 6 of 9, 6 of 8, and 5 of 5 patients by PET, computed tomography (CT),
      endoscopic retrograde cholangiopancreatography (ERCP), and endoscopic ultrasound
      (EUS), respectively. Chronic pancreatitis (CP) was diagnosed in 2 patients. The
      unique appearance on FDG PET made the diagnosis in both these patients. Both
      patients with CP were thought to have a malignancy by CT and EUS and 1 of 2 by
      ERCP. Neuroendocrine tumors were diagnosed in 2 other patients. One of 2 was seen
      by FDG PET and both by CT. CONCLUSIONS: FDG PET can accurately differentiate a
      pancreatic adenocarcinoma from chronic pancreatitis in a patient with a
      suspicious pancreatic mass. Thus, FDG PET may help in establishing a diagnosis
      and subsequently managing a patient with pancreatic disease.

PMID- 9781004
TI  - The C-reactive protein to prealbumin ratio correlates with the severity of
      multiple organ dysfunction.
AB  - BACKGROUND: This study evaluates the correlation between a ratio of two hepatic
      proteins, C-reactive protein (CRP) and prealbumin (PALB), and the severity of
      organ dysfunction as measured by the multiple organ dysfunction score (MODS).
      METHODS: A prospective cohort study was undertaken in critically ill patients (n
      = 70) by measuring the serum levels of CRP and PALB, the energy expenditure via
      indirect calorimetry, and severity of organ dysfunction by the MODS. All three
      variables were recorded for a period of 5 days from admission and then assessed
      for correlation to each other and to the length of stay and mortality in the
      intensive care unit. RESULTS: The CRP/PALB ratio showed a statistically
      significant correlation at 48 hours (r = 0.45, P < .01) and 120 hours (r = 0.53,
      P < .01). This ratio showed higher degrees of correlation when applied to
      patients with a diagnosis of sepsis, multiple organ dysfunction, or single organ
      dysfunction, r = 0.71 and 0.56 at 48 and 120 hours, respectively. Receiver
      operating characteristics (ROC) curves show that a ratio of 2.07 correlated with
      a MODS of 16 with a sensitivity of 92% and a specificity of 71%. CONCLUSIONS:
      This study demonstrates a strong correlation between the severity of organ
      dysfunction and the ratio of two hepatic proteins, CRP and PALB. There was no
      correlation between the degree of energy expenditure and the MODS, Acute
      Physiology and Chronic Health Evaluation II score, or the ratio of CRP/PALB. The
      use of inflammatory markers may be an easy, inexpensive method of assessing
      severity of illness in the critically ill.

PMID- 9781005
TI  - Liver resection using total vascular exclusion.
AB  - BACKGROUND: Total vascular exclusion (TVE) is a technique of liver resection that
      includes controlling both the suprahepatic and infrahepatic vena cava in addition
      to portal inflow at the time of parenchymal transection. We report a series of 61
      liver resections in 60 patients using this technique. METHODS: A retrospective
      review of 61 procedures in 60 patients using TVE between 1990 and 1997 was
      carried out. No patient had cirrhosis. Parameters analyzed included age, gender,
      diagnosis, procedure, operative time, clamp time, intraoperative transfusion
      requirements, postoperative laboratory studies, length of stay (intensive care
      unit, ward), mortality, and morbidity. RESULTS: TVE was sustained hemodynamically
      in all patients. The mean age of the 34 men and 27 women was 56 years (+/- 15
      years); 21% were older than 70 years. Eleven percent of the patients had benign
      lesions; 70% of the malignant tumors were metastatic. Seventy-five percent of the
      procedures were major or extended lobectomies. The mean operative and clamp times
      were 330 +/- 83 and 39 +/- 13.2 minutes, respectively; 68% had clamp times of <
      45 minutes. The mean intraoperative red blood cell units was 1.45 +/- 1.93, with
      a range of 0 to 8 units; 48% required no transfusion and 80% received 2 units or
      less. There was 1 perioperative death for a mortality rate of 1.6%. The morbidity
      rate was 36%, which included 4 patients with postoperative liver dysfunction.
      Complications were not associated with transfusion but with clamp times exceeding
      45 minutes. Liver dysfunction occurred with clamp times more than 60 minutes,
      particularly if the remaining liver parenchyma was histologically abnormal or the
      remnant was small. CONCLUSIONS: TVE is hemodynamically safe, even in patients
      older than 70 years. Blood loss during parenchymal transection is minimal;
      mortality and morbidity are low. The optimal clamp time is less than 45 minutes.
      Liver dysfunction is associated with clamp times exceeding 1 hour, particularly
      if the remaining parenchyma is abnormal or small.

PMID- 9781006
TI  - Laparoscopic and open incisional hernia repair: a comparison study.
AB  - BACKGROUND: Techniques for performing laparoscopic incisional hernia repair have
      been described and some advantages over conventional open repair reported.
      However, most reported series of laparoscopic incisional hernia procedures are
      small, and only one has included a comparison with open repairs. METHODS: From
      December 1993 to January 1998, we prospectively collected operative and outcome
      data on 56 consecutive laparoscopic prosthetic repairs of large incisional
      hernias. The data were compared with those from a retrospective view of 49 open
      incisional hernia repairs done in January 1991 to December 1993. RESULTS: The
      open and laparoscopic repair groups were comparable in patient age, sex,
      preoperative American Society of Anesthesiologists score, hernia size, and
      history of previous repair. Operative time was significantly longer in the
      laparoscopic group; duration of hospitalization and number of perioperative
      complications were significantly greater in the open group. CONCLUSIONS: In this
      series, laparoscopic repair of incisional hernias took longer to perform than
      open repair but was associated with fewer perioperative complications and a
      shorter hospital stay.

PMID- 9781008
TI  - 51st Annual meeting of the American Association of Blood Banks. Philadelphia,
      Pennsylvania, October 31-November 4, 1998. Abstracts.

PMID- 9781007
TI  - Mortality after vascularized pancreas transplantation.
AB  - BACKGROUND: Previous studies have questioned the safety of vascularized pancreas
      transplantation (PTX), particularly because diabetes is an independent risk
      factor for coronary artery disease and cardiac death. METHODS: A retrospective
      analysis of the timing and causes of death after PTX was performed. From April
      1989 through December 1995, 196 PTXs were performed in 186 diabetic patients
      including 134 simultaneous kidney-PTXs, 59 solitary PTXs, and 3 combined liver
      PTXs. All patients underwent whole organ PTX with bladder drainage, received
      triple or quadruple immunosuppression, and had a minimum follow-up of 1 year
      (mean 3.8 years). RESULTS: A total of 22 patients (12%) died at a mean of 19
      months after PTX. Infection was the most common cause of early death, whereas the
      majority of late deaths were due to cardiac causes. In the 8 deaths caused by
      infection, 6 were associated with operative complications, but only 2 received
      excessive immunosuppression for rejection. In the 10 cardiac deaths, 6 patients
      were older than 40 years at the time of PTX and 4 had experienced pancreas graft
      loss before death. Four-year actuarial patient survival was 92% after
      simultaneous kidney-PTX and 87% after solitary PTX. CONCLUSIONS: In this series,
      the mortality rate after PTX was 12%, with infection, myocardial infarction, and
      sudden death accounting for over 80% of deaths. Deaths from infection most
      commonly occurred early and were associated with operative complications, whereas
      cardiac deaths usually were late and related to recipient age or preceded by
      pancreas graft loss. Future strategies aimed at reducing mortality after PTX
      should emphasize appropriate recipient selection and target prevention of
      operative complications.

PMID- 9781009
TI  - Applications of emerging technologies to the study of human genetics.

PMID- 9781010
TI  - In the light of preimplantation genetic diagnosis: some ethical issues in medical
      genetics revisited.

PMID- 9781012
TI  - Fine mapping of Noonan/cardio-facio cutaneous syndrome in a large family.
AB  - Noonan syndrome (NS) is an autosomal dominant condition with facial dysmorphy,
      congenital cardiac defects and short stature. A gene for NS has previously been
      linked to a 14 cM region in 12q24. We performed linkage analysis in a four
      generation Belgian family with NS in some individuals and cardio-facio-cutaneous
      (CFC) syndrome in others. Clinical data and linkage data in this family indicate
      that NS and CFC syndrome result from a variable expression of the same genetic
      defect. We report a maximum lod score of 4.43 at zero recombination for marker
      D12S84 in 12q24. A crossover in this pedigree narrows the candidate gene region
      for NS to a 5 cM interval between markers D12S84 and D12S1341.

PMID- 9781011
TI  - Cellular heterogeneity of CFTR expression and function in the lung: implications
      for gene therapy of cystic fibrosis.
AB  - Cystic fibrosis (CF) has become a paradigm disorder for the clinical testing of
      gene therapies in the treatment of inherited disease. In recent years, efforts
      directed at gene therapy of CF have concentrated on improving gene delivery
      systems to the airway. Surrogate endpoints for complementation of CFTR
      dysfunction in the lung have been primarily dependent on correction of chloride
      transport abnormalities. However, it is now clear that the pathophysiology of CF
      airways disease is far more complex than can be solely attributed to altered
      chloride permeability. For example, in addition to functioning as a chloride
      channel, CFTR also has been implicated in the regulation of other apical membrane
      conductance pathways through interactions with the amiloride sensitive epithelial
      sodium channel (ENaC) and the outwardly rectifying chloride channel (ORCC).
      Superimposed on this functional diversity of CFTR is a highly regulated pattern
      of CFTR expression in the lung. This heterogeneity occurs at both the level of
      CFTR protein expression within different cell types in the airway and the
      anatomical location of these cells in the lung. Potential targets for gene
      therapy of CF include ciliated, non-ciliated, and goblet cells in the surface
      airway epithelium as well as submucosal glands within the interstitium of the
      airways. Each of these distinct cellular compartments may have functionally
      distinct roles in processes which affect the pathogenesis of CF airways disease,
      such as fluid and electrolyte balance. However, it is presently unclear which of
      these cellular targets are most pathophysiologic relevant with regard to gene
      therapy. Elucidation of the underlying mechanisms of CFTR function in the airway
      will allow for the rational design of gene therapy approaches for CF lung
      diseases. This review will provide a summary of the field's current knowledge
      regarding CFTR functional diversity in the airway and the implications of such
      diversity for gene therapies of CF lung disease.

PMID- 9781013
TI  - Short tandem repeat polymorphism evolution in humans.
AB  - Forty-five dinucleotide short tandem repeat polymorphisms were typed in ten large
      samples of a globally distributed set of populations. Although these markers had
      been selected for high heterozygosity in European populations, we found them to
      be sufficiently informative for linkage analysis in non-Europeans.
      Heterozygosity, mean number of alleles, and mean number of private alleles
      followed a common trend: they were highest in the African samples, were somewhat
      lower in Europeans and East Asians, and were lowest in Amerindians. Genetic
      distances also reflected this pattern, and distances modelled after the stepwise
      mutation model yielded trees that were less in agreement with other genetic and
      archaeological evidence than distances based on differentiation by drift (FST).
      Genetic variation in non-Africans seems to be a subset of that in Africans,
      supporting the replacement hypothesis for the origin of modern humans.

PMID- 9781014
TI  - Concentrations of the atherogenic Lp(a) are elevated in FH.
AB  - Lipoprotein(a) (Lp(a)) is a complex in human plasma assembled from low-density
      lipoprotein (LDL) and apolipoprotein(a) (apo(a)). High plasma concentrations of
      Lp(a) are a risk factor for coronary heart disease (CHD) in particular in
      patients with concomitant elevation of LDL. We have analysed for elevated Lp(a)
      levels in patients with familial hypercholesterolaemia (FH), a condition caused
      by mutations in the LDL receptor (LDLR) gene and characterised by high LDL,
      xanthomatosis and premature CHD. To avoid possible confusion by the apo(a) gene
      which is the major quantitative trait locus controlling Lp(a) in the population
      at large, we used a sib pair approach based on genotype information for both the
      LDLR and the apo(a) gene. We analysed 367 family members of 30 South African and
      30 French Canadian index patients with FH for LDLR mutations and for apo(a)
      genotype. Three lines of evidence showed a significant effect of FH on Lp(a)
      levels: (1) Lp(a) values were significantly higher in FH individuals compared to
      non-FH relatives (p < 0.001), although the distribution of apo(a) alleles was not
      different in the two groups; (2) comparison of Lp(a) concentrations in 28 sib
      pairs, identical by descent (i.b.d.) at the apo(a) locus but non-identical for
      LDLR status, extracted from this large sample demonstrated significantly elevated
      Lp(a) concentrations in sibs with FH (p < 0.001); (3) single i.b.d. apo(a)
      alleles were associated with significantly higher Lp(a) concentrations (p <
      0.0001) in FH than non-FH family members. Variability in associated Lp(a) levels
      also depended on FH status and was highest when i.b.d. alleles were present in FH
      subjects and lowest when present in non-FH individuals. The study demonstrates
      that sib pair analysis makes it possible to detect the effect of a minor gene in
      the presence of the effect of a major gene. Given the interactive effect of
      elevated LDL and high Lp(a) on CHD risk our data suggest that elevated Lp(a) may
      add to the CHD risk in FH subjects.

PMID- 9781015
TI  - Mutation at the phenylalanine hydroxylase gene (PAH) and its use to document
      population genetic variation: the Quebec experience.
AB  - We describe variation at the PAH locus in the population of Quebec. We
      successfully analyzed 135 of 141 chromosomes from phenylketonuria (PKU) probands
      (95.7% of the sample), and eight additional chromosomes from a small number of
      probands with non-PKU hyperphenylalaninemia (HPA). The full set of chromosomes
      harboured 45 different PAH mutations: i) seven polymorphisms (IVS2nt19, IVS3nt
      22, IVS6nt-55, Q232Q, V245V, L385L, Y414Y); ii) four mutations causing non-PKU
      HPA (T92I, E390G, R408Q, D415N); iii) 34 mutations causing PKU. Only six
      mutations (M1V, R261Q, F299C, S349P, R408W and IVS12nt1) occurred in the whole
      province at relative frequencies > 5%: most are rare and probably identical by
      descent. By studying associations of mutations with polymorphic haplotype
      alleles, we found examples of mutations on different haplotypes that were
      identical by state, but not by descent because they were recurrent mutations
      (E280K and R408W); and examples of mutations identical both by state and by
      descent because of intragenic recombination (S67P, G218V, V245A and IVS12nt1).
      Ten mutations were first described in Quebec and five are still unique there;
      three of these 'Quebec' mutations are reported here for the first time (c.125A-
      >T (K42I); [c.470G-->A; c.471A--C] (R157N); c.707nt-55 (IVS6nt-55). The PAH
      mutations stratify by geographic region and population, their distributions
      validating hypotheses about European range expansion to North America during
      three separate phases of immigration and demographic expansion in the Quebec
      region over the past four centuries. The PAH homozygosity value (j) is 0.06 for
      the total Quebec sample (0.5-0.08 by regions), and the corresponding homoallelic
      fraction of mutant PAH genotypes is 24%. These findings are a documentation of
      genetic diversity in the Quebec population.

PMID- 9781016
TI  - Complete absence of rib ossification, micrognathia and ear anomalies: extreme
      expression of cerebro-costo-mandibular syndrome?
AB  - We describe a newborn with complete absence of ossification of the ribs, extreme
      micrognathia, absence of external ear canals and the inner ears, and diminished
      mobility in the upper extremities. It is suggested that this represents an
      unusually severe expression of the cerebro-costo-mandibular syndrome. Some
      developmental genes that may have played a role in the pathogenesis are briefly
      reviewed.

PMID- 9781017
TI  - Nail patella syndrome in a cytogenetically balanced t(9;17)(q34.1;q25) carrier.
AB  - Nail patella syndrome (NPS) is an autosomal dominant disorder characterized by
      dysplasia of the nails and patella, decreased mobility of the elbow, iliac horns
      and in some cases nephropathy. Linkage studies have localized the NPS locus to
      chromosome 9q34 within a 1-2 cM interval between D9S60 and the adenylate kinase
      gene (AK1), but the gene has remained elusive. We have identified a balanced
      t(9;17)(q34.1;q25) associated with NPS. By using FISH with probes from 9q the
      breakpoint region was narrowed to a 17.0 cM interval between D9S262 and ABL,
      which includes the NPS critical region. The patient showed the typical clinical
      features of NPS such as hypoplastic, deep-set nails, a dislocated elbow, iliac
      horns, and a polygonal patella. This suggests that the translocation has resulted
      from a break within or near the NPS gene, causing defective expression. The
      translocation in our patient may aid in the identification of the NPS gene.

PMID- 9781018
TI  - Modifier genes in humans: strategies for identification.
AB  - A number of genetic disorders exhibit inter- and intra-familial variability.
      Understanding the factors that control the expression of disease genes should
      provide insight into the fundamental disease processes and will have implications
      for counselling patients. Different mechanisms can account for this variability,
      including environmental factors, genotype-phenotype correlations and imprinting.
      There is also evidence that, in a number of genetic diseases, gene expression is
      under the control of modifier loci. In cases where the biological basis of the
      genetic disease is understood, any genes involved in the pathogenic process
      represent candidate modifier genes which can easily be evaluated. Alternatively,
      modifiers can be identified through approaches such as mouse models. Since
      modifier genes will generally be common and because of confounding environmental
      influences, linkage analyses in humans will generally be based upon affected or
      discordant sib pairs. Discordant sib pairs represent an attractive option for
      linkage studies, because recurrence rates are high and the reduced survival
      characteristics associated with severe phenotypes will make the likelihood of
      obtaining clinical material from two living cases difficult. Furthermore, the use
      of discordant siblings will select for those siblings which possess sufficient
      dissimilarity at the modifier locus to overcome any shared environmental
      influence.

PMID- 9781020
TI  - Phenotype-genotype correlation in Jewish patients suffering from familial
      Mediterranean fever (FMF).
AB  - Familial Mediterranean Fever is one of the most frequent recessive disease in non
      Ashkenazi Jews. The gene responsible for the disease (MEFV) has very recently
      been identified. The M694V ('MED') mutation was found in about 80% of the FMF
      Jewish (Iraqi and North African) chromosomes. To see if the presence of this
      mutation could be correlated with particular traits of the disease, we examined a
      number of clinical features in a panel of 109 Jewish FMF patients with 0, 1 or 2
      MED mutations. We showed that homozygosity for this mutation was significantly
      associated with a more severe form of the disease. In homozygous patients, the
      disease started earlier (mean age 6.4 +/- 5 vs 13.6 +/- 8.9) and both arthritis
      and pleuritis were twice as frequent as in patients with one or no M694V
      mutation. Moreover, 3/3 patients with amyloidosis displayed two MED mutations. No
      association was found with fever, peritonitis, response to colchicine and
      erysipeloid eruption. The present result strongly suggests the potential
      prognostic value of the presence of this mutation.

PMID- 9781019
TI  - The characterization and sequence analysis of thirty CTG-repeat containing
      genomic cosmid clones.
AB  - We have systematically isolated and characterized DNA containing large CTG (n >
      7) repeats from a human cosmid genomic DNA library. Using a CTG10 probe, more
      than 100 cosmid clones were identified, and 30 of these have been extensively
      characterized. The sequenced cosmids contain repeats that are between three and
      19 perfect units (average 10 perfect repeats). The cosmids map to at least 12
      different chromosomes. Sequence analysis of flanking regions suggests that more
      than one third of the repeats occur in exons, and many share strong sequence
      identity with databank sequences, including the gene involved in dentatorubral
      pallidoluysian atrophy (DRPLA). Genotyping of human DNA samples demonstrates that
      more than half of the repeats are polymorphic. This and similar collections of
      clones containing trinucleotide repeats should aid in the identification of genes
      that may contain expansions of trinucleotide repeats involved in human disease.

PMID- 9781021
TI  - Detection of an insertion deletion of region 8q13-q21.2 in a patient with Duane
      syndrome: implications for mapping and cloning a Duane gene.
AB  - Duane syndrome (MIM126800) is an autosomal dominant disease responsible for 1% of
      all strabismus cases and has been related to a 8q12-13 contiguous gene syndrome.
      We report on an insertion of chromosome region 8q13-q21.2 on to band 6q25 in a
      patient presenting with Duane syndrome, mental retardation, and other
      dysmorphisms. FISH analysis using chromosome 8 radiation hybrid LIA2L indicated a
      concurrent deletion within the 8q rearranged region. These results were
      corroborated by STR-PCR analysis and FISH using YAC contig WC8.8 disclosed a
      deletion in 8q13. Comparison of the two known patients with Duane syndrome
      associated with deletion of 8q identifies a small region of overlap (SRO) of < 3
      cM extending from D8S533 and D8S1767 in which a Duane syndrome locus is assigned.
      In addition YAC analysis in our patient showed that 8q rearrangement was rather
      complex since 8q deletion and insertion occurred in two distinct segments
      separated by a region which maintained its location on 8q.

PMID- 9781022
TI  - Chromosome studies in 1792 males prior to intra-cytoplasmic sperm injection: the
      Dutch experience.
AB  - The chance of a male with severe oligozoospermia or azoospermia achieving a
      pregnancy has undergone a revolutionary increase with the introduction of the
      intracytoplasmic sperm injection technique (ICSI). However, since ICSI
      circumvents part of the natural sperm selection mechanisms, the possible
      transmission of genetic defects to the offspring is a major concern. Cytogenetic
      analysis is a relatively simple technique to identify at least the carriers of a
      chromosomal aberration before starting the ICSI procedure. In order to assess the
      frequency of chromosomal aberrations in male ICSI candidates, we have performed a
      nationwide cytogenetic study. Of the 1792 males examined, 72 (4.0%) revealed a
      chromosomal aberration, and one individual even had two. Numerical sex
      chromosomal aberrations and Robertsonian translocations predominated, followed by
      reciprocal translocations, inversions and supernumerary marker chromosomes. The
      different implications, in case a chromosomal aberration is encountered prior to
      ICSI, are discussed.

PMID- 9781023
TI  - MEHMO (mental retardation, epileptic seizures, hypogonadism and -genitalism,
      microcephaly, obesity), a novel syndrome: assignment of disease locus to xp21.1
      p22.13.
AB  - A previously unrecognised X-chromosomal mental retardation syndrome is described.
      Clinical hallmarks are mental retardation, epileptic seizures, hypogonadism, and 
      genitalism, microcephaly and obesity. Life expectancy of patients is less than
      two years. Based on the major clinical symptoms this condition is referred to by
      the acronym MEHMO. Haplotype and two-point linkage analyses in a large three
      generation family assign the disease locus to Xp21.1-p22.13, to a region that is
      flanked by CYBB and DXS365.

PMID- 9781024
TI  - Cytogenetic and molecular study of four couples with multiple trisomy 21
      pregnancies.
AB  - We studied four families each with three trisomy 21 conceptions. In two of the
      families the trisomy 21 conceptions all occurred when the mothers were under 35
      years of age and in the other two families they all occurred when the mothers
      were over 35 years of age. Cytogenetic studies showed low level mosaic trisomy 21
      in the two younger mothers, but not in the two older. In the three families
      tested using molecular techniques the results were consistent with the additional
      chromosome 21 in the trisomic conceptuses being maternally derived. Novel alleles
      were detected in the trisomic offspring of one of the younger mothers,
      demonstrating that the mother had been conceived as a trisomy with three
      different chromosomes 21. Therefore the multiple trisomy 21 pregnancies in the
      two younger mothers resulted from maternal trisomy 21 mosaicism, but may have
      been due to chance in the older mothers.

PMID- 9781025
TI  - Deletion mapping on chromosome 10p and definition of a critical region for the
      second DiGeorge syndrome locus (DGS2).
AB  - DiGeorge syndrome (DGS) is a developmental field defect, characterised by
      absent/hypoplastic thymus and parathyroid, and conotruncal heart defects, with
      haploinsufficiency loci at 22q (DGS1) and 10p (DGS2). We performed fluorescence
      in situ hybridisations (FISH) and polymerase chain reaction (PCR) analyses in 12
      patients with 10p deletions, nine of them with features of DGS, and in a familial
      translocation 10p;14q associated with midline defects. The critical DGS2 region
      is defined by two DGS patients, and maps within a 1 cM interval including D10S547
      and D10S585. The other seven DGS patients are hemizygous for both loci. The
      breakpoint of the reciprocal translocation 10p;14q maps at a distance of at least
      12 cM distal to the critical DGS2 region. Interstitial and terminal deletions
      described are in the range of 10-50 cM and enable the tentative mapping of loci
      for ptosis and hearing loss, features which are not part of the DGS clinical
      spectrum.

PMID- 9781026
TI  - A complete protein truncation test for BRCA1 and BRCA2.
AB  - The protein truncation test (PTT) is currently the fastest method in general use
      for detecting previously unidentified mutations in tumor suppressor genes.
      Greater than three kilobases of coding sequence can be screened by one PCR
      reaction, one coupled in vitro transcription/translation reaction, and one lane
      on an SDS-PAGE gel. The 16 kb of BRCA1/2 coding sequence can be screened with
      nine overlapping segments. Since 90% of BRCA1/2 mutations result in a truncated
      protein product, the theoretical false negative rate for a BRCA1/2 PTT screen
      should be 10%. In practice the false negative rate is much higher, especially
      when cDNA is used as template. However, the actual false negative rate for a
      given screen will depend on the details of how the test is performed. Design of
      the overlapping segments, gel parameters, and nonsense mediated mRNA decay can
      all influence the effectiveness of the screen. BRCA1/2 screening by PTT can be
      optimised by considering these variables. Furthermore, nonsense-mediated mRNA
      decay can be inhibited by blocking protein synthesis with cycloheximide.

PMID- 9781027
TI  - Identical mutation in 55% of the ATM alleles in 11 Norwegian AT families:
      evidence for a founder effect.
AB  - The ATM gene is responsible for the autosomal recessive disorder Ataxia
      Telangiectasia (AT). Many different mutations, located all across the gene, have
      been reported with a predominance of truncating mutations. By using PTT (protein
      truncation test) a mutation was found in one Norwegian AT family. Sequencing
      revealed that the mutation affected nucleotides 3245-3247, codon 1082, and
      changed the sequence from ATC to TGAT, inducing a stop codon downstream at codon
      1095 and leading to early truncation of the ATM protein. Perpendicular DGGE
      (denaturing gradient gel electrophoresis) was used to screen 10 additional
      families for this mutation. The 3245 delATC insTGAT mutation was found in 12 of
      22 proband alleles: five patients were homozygotes and two heterozygotes.
      Haplotype analyses were performed using eight microsatellite markers, within and
      flanking the ATM gene. All carriers of the mutation described were found to have
      a common haplotype of the five closest CA-repeat microsatellite markers.
      Genealogical investigations of the families identified a common ancestor for
      three of the families. The common ancestor was a woman born in 1684 in the area
      from which these families originate. The prevalence of this mutation in Norwegian
      patients now allows a major subset of AT heterozygotes to be identified, both in
      the general population and in breast cancer patients, so that their cancer risk
      can be evaluated.

PMID- 9781028
TI  - A sensorineural progressive autosomal recessive form of isolated deafness,
      DFNB13, maps to chromosome 7q34-q36.
AB  - Deafness is the most frequent sensorineural defect in children. The vast majority
      of the prelingual forms of isolated deafness are highly genetically heterogeneous
      with an autosomal recessive mode of inheritance. Using linkage analysis, we have
      mapped the gene responsible for a severe progressive sensorineural hearing loss,
      DFNB13, segregating in a large consanguineous family living in an isolated region
      in northern Lebanon. A maximum lod score of 4.5 was detected for markers D7S661
      D7S498. Recombination events and homozygosity mapping by descent define a 17 cM
      gene interval in the chromosome region 7q34-q36, between the markers
      D7S2468/D7S2505, on the proximal side, and D7S2439, on the distal side.

PMID- 9781029
TI  - Assignment of gene responsible for progressive pseudorheumatoid dysplasia to
      chromosome 6 and examination of COL10A1 as candidate gene.
AB  - Progressive pseudorheumatoid dysplasia is an autosomal recessive skeletal
      dysplasia with radiographic changes in the spine similar to Spondyleopiphyseal
      dysplasia tarda and clinical, though not radiographic resemblance to rheumatoid
      arthritis. About two-thirds of the reported patients are of Arabic and
      Mediterranean origin which reflects the relative high incidence in this
      population. We performed homozygosity mapping utilising the DNA pooling approach
      to map progressive pseudorheumatoid dysplasia to a chromosomal region on the long
      arm of chromosome 6. We examined a possible candidate gene in the same region of
      linkage, namely COL10A1, for alterations in this disorder. We did not identify
      any mutations in our family, but did not totally exclude COL10A1 gene from being
      the disease-causing gene.

PMID- 9781031
TI  - Integrated physical and transcript map of 5q31.3-qter.
AB  - We have constructed a physical and transcript map of 5q31.3-qter. The contig
      comprises 173 yeast artificial chromosomes (YACs) to which 159 sequence tagged
      sites (STSs), 47 expressed sequence tags (ESTs), and 32 genes were assigned.
      Previously published partial YAC contigs of the region have been refined and
      integrated. Given that the region contains 25 Mbp of DNA the average spacing of
      markers is approximately 100 kb.

PMID- 9781030
TI  - Identification of four novel mutations in severe methylenetetrahydrofolate
      reductase deficiency.
AB  - Severe methylenetetrahydrofolate reductase (MTHFR) deficiency is an inborn error
      of folate metabolism, and is inherited as an autosomal recessive trait. MTHFR is
      a key enzyme in folate-dependent remethylation of homocysteine, and reduces 5,10
      methylenetetrahydrofolate to 5-methyltetrahydrofolate. Patients with this severe
      enzymatic deficiency are biochemically characterised by homocystinuria and
      hypomethioninaemia, and may suffer from neurological abnormalities, mental
      retardation and premature vascular disease. Here we report the molecular basis of
      severe MTHFR deficiency in four unrelated families from Turkish/Greek ancestry.
      By use of reverse-transcriptase (RT)-PCR, subsequently followed by direct
      sequencing analysis, we were able to identify four novel mutations in the MTHFR
      gene: two missense (983A-->G; 1027T-->G) and two nonsense (1084C-->T; 1711C-->T)
      mutations. Furthermore, a splice variant containing a premature termination
      codon, was observed in one patient, probably as a secondary effect of the 1027T-
      >G missense mutation. The ongoing identification and characterisation of
      mutations in the MTHFR gene will provide further insight into the heterogeneity
      of the clinical phenotype in severe MTHFR deficiency.

PMID- 9781033
TI  - Cloning and gene structure of the rod cGMP phosphodiesterase delta subunit gene
      (PDED) in man and mouse.
AB  - Rod-specific cGMP phosphodiesterase (PDE) is a key enzyme of the
      phototransduction cascade, and mutations in its catalytic subunits have been
      associated with retinal degenerative diseases. The bovine delta-subunit
      solubilises the normally membrane-bound PDE and is the only subunit expressed in
      extraocular tissues. We isolated the human and mouse orthologs, and found 78%
      identity at the DNA level and 98% identity at the protein level. The
      Caenorhabditis elegans homolog shows 69% identity at the protein level. The human
      PDED gene consisted of 5 exons spanning at least 30 kb of genomic DNA. Northern
      blot analysis showed a 1.3 kb transcript in human retina, heart, brain, placenta,
      liver, and skeletal muscle. Fluorescence in situ hybridisation (FISH) and
      radiation hybrid mapping localised the human PDED gene to chromosome 2q37. A
      preliminary screen of all 5 exons in 20 unrelated patients with autosomal
      recessive retinitis pigmentosa revealed no PDED mutations.

PMID- 9781032
TI  - Linkage of AD HSP and cognitive impairment to chromosome 2p: haplotype and
      phenotype analysis indicates variable expression and low or delayed penetrance.
AB  - We report linkage of a family affected with autosomal dominant hereditary spastic
      paraparesis (HSP) and/or cognitive impairment to the HSP locus on chromosome 2p.
      To date all families linked to this locus have been affected with 'pure' HSP. The
      specific pattern of cognitive impairment in this family is characterised
      primarily by deficits in visuo-spatial functions. We also present genetic studies
      that indicate variable expression and low or delayed penetrance. We have
      constructed a haplotype flanked by polymorphic markers D2S400 and D2S2331 that
      was present in 12 individuals affected with spastic paraparesis. The severity of
      spasticity varied markedly among these individuals. In addition four of these
      individuals (aged 62-70) also had a specific form of cognitive impairment. The
      disease haplotype was also present in an individual (age 57) who had an identical
      pattern of cognitive impairment as the only sign of the disease supporting the
      hypothesis that spastic paraparesis and cognitive impairment are the result of
      variable expression of a single gene (rather than a co-incidental occurrence).
      Haplotype reconstruction for all participating family members revealed the
      presence of this disease haplotype in six individuals who had normal neurological
      and neuropsychological examinations. All six are below the maximal age of onset
      in the family--60 years. This is evidence for low or late penetrance of the AD
      HSP gene in this family. The identification of normal individuals carrying the
      disease haplotype demonstrates the importance of genetic studies in combination
      with clinical examination when counselling at risk family members.

PMID- 9781034
TI  - Spectrum of ABCR gene mutations in autosomal recessive macular dystrophies.
AB  - Stargardt disease (STGD) and late-onset fundus flavimaculatus (FFM) are autosomal
      recessive conditions leading to macular degenerations in childhood and adulthood,
      respectively. Recently, mutations of the photoreceptor cell-specific ATP binding
      transporter gene (ABCR) have been reported in Stargardt disease. Here, we report
      on the screening of the whole coding sequence of the ABCR gene in 40 unrelated
      STGD and 15 FFM families and we show that mutations truncating the ABCR protein
      consistently led to STGD. Conversely, all mutations identified in FFM were
      missense mutations affecting uncharged amino acids. These results provide the
      first genotype-phenotype correlations in ABCR gene mutations.

PMID- 9781035
TI  - Migraine, ataxia and epilepsy: a challenging spectrum of genetically determined
      calcium channelopathies. Dutch Migraine Genetics Research Group.
AB  - Clinical and genetic heterogeneity as well as influence of environmental factors
      have hampered identification of the genetic factors which are involved in
      episodic diseases such as migraine, episodic ataxia and epilepsy. The study of
      rare, but clearly genetically determined subtypes, may help to unravel the
      pathogenesis of the more common forms. Recently, different types of mutation in
      the brain-specific P/Q type calcium channel alpha 1A subunit gene (CACNA1A) on
      chromosome 19p13 were shown to be involved in three human disorders: familial
      hemiplegic migraine (FHM), episodic ataxia type 2 (EA2), and chronic
      spinocerebellar ataxia type 6 (SCA6). In addition, evidence is accumulating that
      the same gene is also involved in the common forms of migraine with and without
      aura. In the tottering and leaner mouse, which are characterised by epilepsy and
      ataxia, similar mutations were identified in the mouse homologue of the calcium
      channel alpha 1A subunit gene. These findings add to the growing list of episodic
      (and now also chronic) neurological disorders, which are caused by inherited
      abnormalities of voltage-dependent ion channels. The findings in migraine
      illustrate that rare, but monogenic variants of a disorder, may be successfully
      used to identify candidate genes for the more common, but genetically more
      complex, forms.

PMID- 9781036
TI  - Identification of fifteen novel mutations in the tissue-nonspecific alkaline
      phosphatase (TNSALP) gene in European patients with severe hypophosphatasia.
AB  - Hypophosphatasia is an inherited disorder characterised by defective bone
      mineralisation and deficiency of serum and tissue liver/bone/kidney alkaline
      phosphatase (L/B/K ALP) activity. We report the characterisation of tissue
      nonspecific alkaline phosphatase (TNSALP) gene mutations in a series of 13
      European families affected by perinatal, infantile or childhood hypophosphatasia.
      Eighteen distinct mutations were found, only three of which had been reported
      previously in North American and Japanese populations. Most of the 15 new
      mutations were missense mutations, but we also found two mutations affecting
      donor splice sites and a nonsense mutation. A missense mutation in the last codon
      of the putative signal peptide probably affects the final maturation of the
      protein. Despite extensive sequencing of the gene and its promotor region, only
      one mutation was identified in two cases, one of which was compatible with a
      possible dominant effect of certain mutations and the putative role of
      polymorphisms of the TNSALP gene. In 12 of the 13 tested families, genetic
      diagnosis was possible by characterisation of the mutations or by use of
      polymorphisms as genetic markers. Hypophosphatasia diagnosis was assigned in two
      families where clinical, laboratory and radiographic data were unclear and
      prenatal diagnosis was performed in one case. The results also show that severe
      hypophosphatasia is due to a very large spectrum of mutations in European
      populations with no prevalent mutation and that genetic diagnosis of the disease
      must be performed by extensive analysis of the gene.

PMID- 9781037
TI  - Genetic diversity in northern Spain (Basque Country and Cantabria): GM and KM
      variation related to demographic histories.
AB  - Genetic diversity in Northern Spain (SW Europe) was assessed through the analysis
      of the GM and KM immunoglobulin markers in 505 individuals using a set of 17
      allotypes, including the G2M(23) allotype which has been infrequently used before
      now. The individuals were representative of three anthropologically well-defined
      populations belonging to two geographically and archaeologically distinct areas
      in the Basque Country (Guipuzcoa and Alava provinces) and to the mountainous
      region of Montes de Pas in the province of Cantabria. Gene frequency
      distributions indicated a high genetic divergence between Montes de Pas and the
      Basque Country, and a relative degree of heterogeneity between the two Basque
      regions. The genetic differentiation of Montes de Pas, which is consistent with
      previous classical polymorphism analyses, suggests a considerable genetic
      variation range within the Iberian Peninsula, possibly higher than that often
      polarised around the Basque versus non-Basque variation. Analyses of genetic
      structure show that the major differentiation of Montes de Pas could be related
      to the historically documented mixed origin of this population. The moderate
      genetic distances between regions in the Spanish Basque Country could be
      explained by differential systematic pressures acting through a stronger gene
      flow in the South than in the more isolated Northern areas. The comparisons with
      neighbouring populations from the French Pyrenees suggest that the present
      genetic variation revealed by lg polymorphisms in SW Europe can be related to
      historical demographic processes including gene flow and/or low population sizes.

PMID- 9781038
TI  - Genomic organization of the MTM1 gene implicated in X-linked myotubular myopathy.
AB  - X-linked recessive myotubular myopathy (XLMTM) is a very severe congenital
      muscular disease characterised by an impaired maturation of muscle fibres, and
      caused by defects in the MTM1 gene. This gene defines a new family of putative
      tyrosine phosphatases conserved through evolution. We have determined intronic
      flanking sequences for all the 15 exons to facilitate the detection of mutations
      in patients and genetic counselling. We characterised a new polymorphic marker in
      the immediate vicinity of the gene, which might prove useful for linkage
      analysis. Sequencing of the TATA-less predicted promoter provides the basis for
      transcriptional regulatory studies.

PMID- 9781039
TI  - Absence of homozygosity for predominant mutations in PMM2 in Danish patients with
      carbohydrate-deficient glycoprotein syndrome type 1.
AB  - Carbohydrate-deficient glycoprotein syndrome type 1 (CDG1; McKusick No. 212065)
      is an autosomal recessively inherited disease characterised clinically by central
      nervous system dysfunction and biochemically by hypoglycosylation of many serum
      proteins. Most patients with CDG1 have deficient activity of phosphomannomutase.
      The locus for this enzyme has been mapped to 16p13, and a gene, PMM2, encoding
      phosphomannomutase has been isolated. We identified 34 mutations on 36 disease
      chromosomes in 18 unrelated Danish patients with CDG1. All patients have less
      than 15% residual activity of phosphomannomutase. Two mutations account for 88%
      of all mutations: F119L and R141H were each found in 16 out of 36 CDG1 alleles.
      These two mutations were found to be in linkage disequilibrium with two different
      alleles of the marker D16S3020, suggesting that there is one ancestral origin for
      each mutation. Two new mutations, G117R and D223E, were identified also.
      Surprisingly, no patient was homozygous for either of the two common mutations,
      suggesting that homozygosity for these mutations is either lethal or so benign
      that such patients are not detected.

PMID- 9781040
TI  - Isolation of a novel human voltage-dependent anion channel gene.
AB  - The voltage-dependent anion channel of the mitochondrial outer membrane (VDAC) is
      a small, abundant pore-forming protein found in the outer membranes of all
      eukaryotic mitochondria. The VDAC protein is believed to control the movement of
      adenine nucleotides through the outer membrane and to be the mitochondrial
      binding site for hexokinase and glycerol kinase. Two human VDAC cDNAs (HVDAC1 and
      HVDAC2) have been previously isolated and mapped on chromosome X and 21,
      respectively. Here, we report the isolation of a novel third human VDAC cDNA,
      corresponding to the mouse MVDAC3 gene. The expression of this gene in various
      tissues and its chromosomal localization by polymerase chain reaction (PCR) using
      a human/rodent somatic cell mapping panel and by fluorescence in situ
      hybridization is also presented.

PMID- 9781041
TI  - A second middle eastern kindred with autosomal recessive non-syndromic hearing
      loss segregates DFNB9.
AB  - A second kindred has been identified which supports the previously reported
      location of DFNB9. Linkage has been established to markers closely linked to
      DFNB9 which is located on 2p22-p23. The hearing impaired individuals in this
      highly consanguineous kindred from Eastern Turkey have prelingual profound
      hearing loss which affects all frequencies. A genetic map of the 2p22-p23 region
      where DFNB9 resides was generated using marker genotypes available from the CEPH
      database. All markers were placed on this genetic map using a likelihood ratio
      criterion of 1000:1. This map suggests that the region for DFNB9 is less than
      1.08 cM, 95% confidence interval (0-2.59 cM).

PMID- 9781042
TI  - Linkage analysis in two large Italian pedigrees affected with nail patella
      syndrome.
AB  - Nail patella syndrome (NPS) or osteo-onychodysplasia, is an autosomal dominant
      disorder characterised by nail dysplasia, absent or hypoplastic patellae, iliac
      horns and nephropathy. Previous studies have demonstrated linkage of the nail
      patella locus to the ABO and adenylate kinase loci on human chromosome 9q34.
      Recently, informative recombination events placed the NPS locus within a 1-2 cM
      interval within D9S60 and the AK1 gene. We describe here linkage analysis
      performed in two large Italian pedigrees with 10 and 11 members affected,
      respectively. A set of highly informative markers have been analysed and the
      allele segregation in the two families confirmed the linkage to chromosome 9. The
      presence of three recombination events allows definition of the critical region
      with a centrometric boundary between markers D9S1881 and D9S1840 and a telomeric
      boundary between markers D9S315 and D9S290.

PMID- 9781043
TI  - Crossing over analysis at pachytene in man.
AB  - The distribution of anti-MLH1 (MutL homologue 1) antibody labelling was studied
      in human prophase meiocytes. A labelling pattern consisting of distinct foci,
      always associated with the synaptonemal complex (SC) and never in closely
      juxtaposed pairs, was observed. Comparison of the number and general positions of
      autosomal foci with previous studies of the number and positions of autosomal
      chiasmata indicates that the anti-MLH1 antibody marks sites of crossing over in
      human pachytene spermatocytes. A mean number of 50.9 autosomal foci was observed
      from 46 human pachytene spermatocytes corresponding to a genetic length of 2545
      cm. Division of these spermatocytes into sub-stages revealed that the number of
      foci remains stable throughout pachytene. A focus was found on the XY bivalent in
      56.5% of the nuclei. The presence or absence of foci from the XY bivalent could
      not be correlated to pachytene sub-stage.

PMID- 9781044
TI  - Asynchronous replication of allelic loci in Down syndrome.
AB  - We have used FISH to determine the level of synchronisation in replication timing
      of four pairs of alleles, unrelated to chromosome 21 (p53, HER2, RB1, and c-myc),
      in foetal (amniotic fluid) cell samples of Down syndrome and in normal foetuses.
      All samples derived from the Down syndrome subjects showed large temporal
      differences in replication timing, in contrast to the high level of synchrony
      shown in all samples of normal individuals. Thus, as judged by four independent
      loci which are not associated with chromosome 21, the additional chromosome in
      the Down syndrome genome induces changes in the replication pattern of an allelic
      pair: from a synchronous pattern characteristic to concomitantly expressed
      alleles to an unsynchronised one shown by alleles displaying an allele-specific
      mode of expression.

PMID- 9781045
TI  - mtDNA analysis of the Galician population: a genetic edge of European variation.
AB  - Analysis of mitochondrial DNA (mtDNA) variation has become a useful tool for
      human population studies. We analysed the first hypervariable region of
      mitochondrial DNA control region (position 16024-16383) in 92 unrelated
      individuals from Galicia (Spain), a relatively isolated European population at
      the westernmost continental edge. Fifty different sequences defined by 56
      variable positions were found. The frequency of the reference sequence reaches in
      Galicians its maximum value in Europe. Moreover, several genetic indexes confirm
      the low variability of our sample in comparison to data from 11 European and
      Middle Eastern populations. A parsimony tree of the sequences reveals a high
      simplicity of the tree, with few and small well defined clusters. These results
      place Galicians on the genetic edge of the European variation, bringing together
      all the traits of a cul-de-sac population with a striking similarity to the
      Basque population. The present results are fully compatible with a population
      expansion model in Europe during the Upper Paleolithic age. The genetic evidence
      revealed by the analysis of mtDNA shows the Galician population at the edge of a
      demographic expansion towards Europe from the Middle East.

PMID- 9781046
TI  - Localisation of the gene for a dominant congenital spinal muscular atrophy
      predominantly affecting the lower limbs to chromosome 12q23-q24.
AB  - Spinal muscular atrophies are a heterogeneous group of disorders. They differ in
      time of onset, clinical presentation, progression, severity and mode of
      inheritance. In 1985 a Dutch family was described with a dominant, non
      progressive spinal muscular atrophy presenting at birth with arthrogryposis (MIM
      600175). Linkage analysis was performed in this family. After having excluded the
      loci for Werdnig-Hoffmann's disease and for dominant distal spinal muscular
      atrophy with upper limb predominance, we were able to localise the gene to a 10
      cM interval between the markers D12S78 and D12S1646 on chromosome 12q23-q24.
      Recently, dominant scapuloperoneal spinal muscular atrophy has been localised to
      an overlapping interval. However, the clinical appearances of scapuloperoneal
      spinal muscular atrophy and the present disorder make allelism unlikely. In 1994,
      a second Dutch family with a disorder similar to the present one was described.
      We excluded linkage to markers of the 12q23-q24 region in this family and thereby
      proved genetic heterogeneity of this type of dominant, congenital and
      nonprogressive spinal muscular atrophy.

PMID- 9781047
TI  - Mitochondrial DNA analysis on remains of a putative son of Louis XVI, King of
      France and Marie-Antoinette.
AB  - Carl Wilhelm Naundorff was buried in 1845 in Delft as Louis Charles, Duc de
      Normandie, 'Louis XVII'. However, the son of Louis XVI and Marie-Antoinette-Louis
      XVII--officially died in the Temple of Paris in 1795. In order to resolve the
      identity of Naundorff, mitochondrial DNA (mtDNA) D-loop sequences of his remains
      were compared with the sequences obtained from the hairs of two sisters of Marie
      Antoinette, Marie-Antoinette herself, and with the sequences obtained from DNA
      samples of two living maternal relatives. The mtDNA sequence of a bone sample
      from Naundorff showed two nucleotide differences from the sequences of the three
      sisters and four differences from the sequences of living maternal relatives.
      Based on this evidence it becomes very unlikely that Naundroff is the son of
      Marie-Antoinette.

PMID- 9781048
TI  - Severe limb girdle muscular dystrophy in Spanish gypsies: further evidence for a
      founder mutation in the gamma-sarcoglycan gene.
AB  - Limb-girdle muscular dystrophy type 2C (LGMD2C) is an autosomal recessive
      muscular dystrophy with primary gamma-sarcoglycan deficiency, generally
      associated with a severe clinical course. gamma-sarcoglycan, a 35kDa dystrophin
      associated protein, is encoded by a single gene on chromosome 13q12. Six
      different mutations have been described in that gene, and it has been proved they
      are the origin of the disease. One of these mutations (C283Y), a G-->A transition
      in codon 283, was recently and exclusively identified in Gypsy patients from
      different European countries. We report the study of 11 LGMD2C unrelated Gypsy
      families (nine Spanish and two Portugese). The muscle biopsies of these patients
      showed a drastically decreased immunostaining with alpha and gamma-sarcoglycan
      antibodies. All the patients were homozygous for C283Y missense mutation, and all
      affected chromosomes (patients and heterozygous relatives) carried the allele 5
      (112 bp) of the intragenic microsatellite D13S232. Unexpectedly, this allele is
      most frequent in the Caucasian population but not in the normal Gypsy population.
      The clinical severity of all patients demonstrates that the C283Y missense
      mutation in a homozygous state causes a severe LGMD2C (DMD-like). The elevated
      number of families ascertained let us assume that LGMD2C is prevalent in the
      Gypsy population, and that all the families have inherited a founding mutation.

PMID- 9781049
TI  - Refined mapping of the gene encoding the p127 kDa UV-damaged DNA-binding protein
      (DDB1) within 11q12-q13.1 and its exclusion in Best's vitelliform macular
      dystrophy.
AB  - Best's vitelliform macular dystrophy (Best's disease) is an autosomal dominant
      disorder of unknown causes and is typically characterised by an accumulation of
      lipofuscin-like material in the subretinal space of the macula. The disease gene
      has been localised to chromosome 11q12-13.1 within a 1.4 Mbp interval flanked by
      markers at D11S1765 and uteroglobin (UGB). Here we report the refined mapping of
      the gene encoding the p127 kDa subunit (DDB1) of a UV damage-specific DNA binding
      protein within the D11S1765-UGB region. Northern blot analysis demonstrates an
      abundant expression of the DDB1 transcript in the retina suggesting a functional
      role for DDB1 in this tissue. These considerations together with the chromosomal
      localisation have led us to evaluate the possible involvement of DDB1 in the
      pathogenesis of Best's disease.

PMID- 9781050
TI  - A very high density microsatellite map (1 STR/41 kb) of 1.7 Mb on Xp22 spanning
      the microphthalmia with linear skin defects (MLS) syndrome critical region.
AB  - Microphthalmia with linear skin defects (MLS) syndrome is an X-linked disorder
      presenting only in XX individuals. It is characterised by dysmorphic features
      such as microphthalmia, sclerocornea, and linear streaks of erythematous and
      hypoplastic skin restricted to the head and neck. Karyotype analyses have so far
      revealed a terminal deletion or translocation causing monosomy for the distal Xp
      region (Xp22.3) in all patients. We have used existing cosmid clones from the
      region to perform a saturation screen for AC-type microsatellites with the goal
      of facilitating analysis of five novel patients with features of MLS. Three of
      these cases had an Xp22.3 abnormality, while the other two showed some
      characteristic features of MLS but had apparently normal karyotypes. Forty-two
      novel microsatellite markers have now been developed from the 1.7 Mb cloned
      interval. Ninety-three percent of the novel markers exhibited allelic variation,
      representing an average of one polymorphic PCR-based marker (STR) every 41 kb.

PMID- 9781051
TI  - Educational material on genetics for schools: 'the science behind the Jeans for
      Genes Day'.

PMID- 9781052
TI  - Prenatal diagnosis in CDG1 families: beware of heterogeneity.
AB  - Carbohydrate-deficient glycoprotein syndrome type 1 (CDG1) is an autosomal
      recessive, metabolic disorder with severe psychomotor retardation and a high
      mortality rate in early childhood. Most patients have a deficiency of
      phosphomannomutase, due to mutations in PMM2, a gene located on chromosome 16p13.
      Over a period of 18 months we offered prenatal diagnosis to eight families. In
      six cases and prior to the identification of the gene, the diagnosis was based on
      linkage analysis and phosphomannomutase measurements. Subsequently direct
      mutation analysis has been used in two families. It is shown here that
      phosphomannomutase activities are strongly reduced in cultured amniocytes and
      trophoblasts of affected foetuses. We refrained from offering prenatal testing in
      two other families, because either the disease did not link to chromosome 16
      and/or normal phosphomannomutase activities were measured in fibroblasts from the
      proband. This confirms earlier suggestions of heterogeneity for CDG1.

PMID- 9781053
TI  - Generation of a transcription map of a 1 Mbase region containing the HFE gene
      (6p22).
AB  - A transcription map was generated of a 1 Mb interval including the HFE gene on
      6p22. Thirty-seven unique cDNA fragments were characterised following their
      retrieval from hybridisation of immobilised YACs to primary pools of cDNAs
      prepared from RNA of foetal brain, human liver, foetal human liver, placenta, and
      CaCo2 cell line. All cDNA fragments were positioned on the physical map on the
      basis of presence in aligned and overlapping YACs and cosmid clones of the
      region. The isolated cDNAs together with established or published sequence tagged
      sites (STSs) and markers provided sufficient landmark density to cover
      approximately 90% of the 1 Mb interval with cosmid clones. The precise
      localisation of two known genes (NPT1 and RING finger protein) was established. A
      minimum of 14 additional transcription units has also been integrated. Twenty
      eight cDNA fragments showed no similarity with known sequences, but 20 of these
      detected discrete mRNAs upon northern analysis. Their characterisation is still
      under investigation. Eleven new polymorphisms were also identified and localised,
      and the HFE genomic structure was better defined. This integrated transcription
      map considerably extends a recently published map of the HFE region. It will be
      useful for the identification of genetic defects mapping to this region and for
      providing template resources for genomic sequencing.

PMID- 9781054
TI  - Evidence against a major role of PEG1/MEST in Silver-Russell syndrome.
AB  - Silver-Russell syndrome (SRS) is a heterogeneous disorder characterised by
      interauterine and postnatal growth retardation, with or without additional
      dysmorphic features. Most cases are sporadic but a few familial cases have been
      described. A subset of patients exhibit maternal uniparental disomy for
      chromosome 7 (mUPD7) strongly suggesting that genomic imprinting plays a role in
      the aetiology of the disease. We and others have recently characterised the human
      PEG1/MEST gene, the first imprinted gene known to be located on chromosome 7.
      Although the function of PEG1/MEST is unknown, the paternal-specific expression
      of this gene and its location at 7q32, render it a promising candidate for SRS.
      As a prerequisite for mutation screening in 49 patients with SRS and 9 with
      primordial growth retardation (PGR), we determined the complete genomic structure
      of the PEG1/MEST gene which consists of 12 exons. Apart from one silent mutation
      and two novel polymorphisms, nucleotide changes were not detected in any of these
      patients. Moreover, methylation patterns of the 5' region of PEG1/MEST were found
      to be normal in 35 SRS and 9 PGR patients and different from the pattern seen in
      patients with mUPD7. These findings strongly argue against a role of PEG1/MEST in
      the majority of Silver-Russell syndrome cases.

PMID- 9781055
TI  - A novel 25 bp tandem repeat within the human trefoil peptide gene TFF2 in
      21q22.3: polymorphism and mammalian evolution.
AB  - Trefoil peptides belong to a family of small secretory proteins characterised by
      three intrachain disulfide bonds forming the trefoil motif (TFF-domain). They
      serve to maintain or repair the epithelial mucosa, and promote cell migration.
      They are predominantly found in gastrointestinal tissues, and are upregulated
      around areas of epithelial damage, and in meta- and neoplasia. The corresponding
      three genes are clustered in human 21q22.3. TFF2 is the only human one encoding
      two TFF-domains on separate exons. In between (intron 2), a novel 25 bp sequence
      is located that is tandemly repeated approximately 48 times, but is unique in the
      human genome. A diallelic polymorphism with a second allele comprising
      approximately 53 repeat units is present among individuals. Both alleles were
      cloned on BAC recombinants. In Caucasians (n = 78) the allele frequencies found
      are 0.85 and 0.15, respectively, representing a frequency of heterozygosity of
      26%. Ape and monkey species exhibit homologous repeats of shorter total array
      length, whereas none is found in other mammals.

PMID- 9781056
TI  - Heterozygous mutation in the pore of potassium channel gene KvLQT1 causes an
      apparently normal phenotype in long QT syndrome.
AB  - Mutations in KvLQT1, a gene encoding a potassium channel, cause both the
      recessive Jervell and Lange-Nielsen (JLN) syndrome and the dominant Romano-Ward
      (RW) syndrome. These diseases are characterised by a prolonged QT interval on the
      ECG, syncopes and sudden death due to cardiac arrhythmias. The JLN syndrome is
      also associated with a congenital bilateral deafness. We report here a novel
      missense mutation, W305S, in the pore region of KvLQT1 identified by PCR-SSCP
      analysis in two consanguineous JLN families. In contrast to several missense
      mutations found in the same region of KvLQT1 in RW patients which are associated
      with severe cardiac phenotypes, the W305S mutation is responsible for an
      apparently normal phenotype in heterozygous JLN carriers.

PMID- 9781057
TI  - BRCA2 germline mutations in Swedish breast cancer families.
AB  - Mutations in the breast cancer susceptibility gene (BRCA2) are believed to be
      responsible for a significant fraction of hereditary breast cancer. To determine
      the BRCA2 mutation spectrum in a subset of Swedish breast cancer families, 162
      families were screened for germline mutations in this gene. A combination of RT
      PCR, PTT and direct DNA sequencing was used. Two mutations and one previously
      reported polymorphic variant resulting in a truncated protein were identified.
      Our data suggest that only a small proportion of Swedish breast cancer families
      is attributable to BRCA2 germline mutations. This result, in combination with the
      low frequency of BRCA1 germline mutations identified in our previous study,
      suggests additional high penetrant as well as low penetrant breast cancer
      susceptibility genes are involved in familial breast cancer.

PMID- 9781058
TI  - Isochromosomes 12p and 9p: parental origin and possible mechanisms of formation.
AB  - In a recent study Bugge et al and Kotzot et al reported that isochromosomes 18p
      originate mainly from maternal meiosis II nondisjunction, followed by
      misdivision. In order to determine if there is a common mechanism for
      isochromosome formation, three cases with mosaicism for an additional
      isochromosome 12p and three cases with tetrasomy 9p were studied. Two probands
      with isochromosomes 12p and the three cases with isochromosome 9p showed 3
      alleles (two different maternal alleles and one paternal allele) at several loci
      mapping to distal 12p and 9p, respectively. Maternal heterozygosity for distal
      markers was reduced to homozygosity for markers closer to the centromere in both
      i(12p) cases and in one i(9p) case. For one patient with isochromosome 12p, the
      maternal band was clearly stronger than the paternal one at some loci, but two
      distinct maternal alleles were never seen. For one foetus and the patient with
      tetrasomy 9p, distal markers showed maternal heterozygosity. All proximal markers
      were not informative in these two i(9p) cases. Our findings indicate common
      features in different autosomal isochromosomes: the origin of the isochromosomes
      analysed in predominantly maternal; and a common mechanism appears to underlie
      their formation, namely due to meiosis II nondisjunction followed by a
      rearrangements leading to duplication of the short and loss of the long arm.

PMID- 9781059
TI  - Comparison of conformation-sensitive gel electrophoresis and single-strand
      conformation polymorphism analysis for detection of mutations in the BRCA1 gene
      using optimized conformation analysis protocols.
AB  - In order to develop a selective mutation screening strategy for BRCA1, one of the
      gene responsible for hereditary predisposition to breast cancer, we analysed by
      single-strand conformation polymorphism (SSCP) and conformation-sensitive gel
      electrophoresis (CSGE) a cohort of 20 Bulgarian breast cancer patients,
      prescreened for nonsense mutations by the protein truncation test. By assaying
      the complete coding sequence of the gene applying both methods, we were able to
      detect 12 sequence alterations: 11 nucleotide substitutions and one deletion. Two
      of the alterations are intronic polymorphisms, the rest are exon sequence
      variants. Of the 12 polymorphisms identified, 11 are described and one is new.
      All sequence changes were detected by CSGE and eight of them were also shown by
      SSCP analysis. There was no sequence alterations which could be detected by SSCP
      analysis only. We propose that because of the specificity of most sequence
      variants detected (nucleotide substitutions) and the comparatively high
      percentage of AT content of the BRCA1 gene (58.4%), CSGE turned out to be the
      more sensitive technique in our assay. This observation is in agreement with
      other accepted analysis strategies for BRCA1 and it may prove useful for mutation
      screening of AT-rich, multi-exon genes.

PMID- 9781061
TI  - Human EGFR, a candidate gene for the Silver-Russell syndrome, is biallelically
      expressed in a wide range of fetal tissues.
AB  - Maternal uniparental disomy of chromosome 7 (mUPD7) has been reported in around
      10% of cases of Silver-Russell syndrome (SRS). This suggests that at least one
      gene on chromosome 7 is imprinted and involved in the pathogenesis of this
      condition. One candidate is epidermal growth factor receptor (EGFR) which maps to
      chromosome 7p12, a region homologous to an imprinted region on mouse chromosome
      11. Using a restriction fragment length polymorphism, biallelic expression of
      EGFR was found in a range of normal human fetal tissues. Expression was also
      demonstrated in fibroblasts and lymphoblasts from SRS patients with mUPD7. Thus
      no evidence that EGFR is imprinted was found, making its involvement in SRS
      unlikely. However, EGFR was shown to be widely expressed in the human fetus,
      evidence that this gene plays an important role in early development.

PMID- 9781060
TI  - First-stage autosomal genome screen in extended pedigrees suggests genes
      predisposing to low bone mineral density on chromosomes 1p, 2p and 4q.
AB  - Osteoporosis is characterized by low bone density, and osteopenia is responsible
      for 1.5 million fractures in the United States annually. In order to identify
      regions of the genome which are likely to contain genes predisposing to
      osteopenia, we genotyped 149 members of seven large pedigrees having recurrence
      of low bone mineral density (BMD) with 330 DNA markers spread throughout the
      autosomal genome. Linkage analysis for this quantitative trait was carried out
      using spine and hip BMD values by the classical lod-score method using a genetic
      model with parameters estimated from the seven families. In addition, non
      parametric analysis was performed using the traditional Haseman-Elston approach
      in 74 independent sib pairs from the same pedigrees. The maximum lod score
      obtained by parametric analysis in all families combined was +2.08 (theta = 0.05)
      for the marker CD3D on chromosome 11q. All other combined lod scores from the
      parametric analysis were less than +1.90, the threshold for suggestive linkage.
      Non-parametric analysis suggested linkage of low BMD to chromosomes 1p36 (Zmax =
      +3.51 for D1S450) and 2p23-24 (Zmax = +2.07 for D2S149). Maximum multi-point lod
      scores for these regions were +2.29 and +2.25, respectively. A third region with
      associated lod scores above the threshold of suggestive linkage in both single
      point and multi-point non-parametric analysis was on chromosome 4qter (Zmax =
      +2.95 for D4S1539 and Zmax = +2.48 for D4S1554). Our data suggest the existence
      of multiple genes involved in controlling spine and hip BMD, and indicate several
      candidate regions for further screening in this and other independent samples.

PMID- 9781062
TI  - Evaluation of CFTR gene mutation testing methods in 136 diagnostic laboratories:
      report of a large European external quality assessment.
AB  - Within the framework of the European Concerted Action on Cystic Fibrosis (Biomed
      2, BMH4-CT96-0462) a quality assessment was set up for 135 European and one
      Australian laboratory. Six DNA samples were sent to the various laboratories.
      These samples carried the following CFTR genotypes: dF508/N1303K; dI507/wild;
      dF508/G551D; dF508/621 + 1 GtoT; R553X/wild and 1717-1 GtoA/wild. Each laboratory
      was asked to process the samples as they routinely do, whether they checked for
      all mutations or not. More than 75% of the laboratories screened for at least six
      of these mutations. Heteroduplex analysis was the most frequently used primary
      testing method (47%), in many instances followed by restriction enzyme digestion.
      Only a minority of the laboratories made use of a commercial CFTR mutation
      detection kit. On average, 91% of the laboratories correctly typed both alleles
      of a given DNA sample. However, 35% of the laboratories incorrectly typed one or
      more alleles from a total of 12 alleles included in the trial. One laboratory
      even failed to identify four of the different alleles correctly. The genotyping
      error frequency tended to be lower in laboratories which perform more than 200
      CFTR mutation analyses per year. The results of this quality control trial
      suggest that there are many laboratories (35%) which have a percentage of errors
      unacceptable in a routine testing setting. The development of a consensus testing
      strategy for routine diagnostic laboratories and centralised mutation analysis
      facilities for rare or country-specific mutations in a limited number of expert
      centres, in combination with regular training sessions and quality assessments,
      should further improve genotyping.

PMID- 9781063
TI  - Germline mutational analysis of presenilin 1 and APP genes in Jewish-Israeli
      individuals with familial or early-onset Alzheimer disease using denaturing
      gradient gel electrophoresis (DGGE).
AB  - Germ line mutations in three genes have been detected in patients with familial
      Alzheimer's disease (FAD) and sporadic, early onset disease: amyloid precursor
      protein (APP), presenilin 1 (PS-1), and presenilin 2 (PS-2). The relative
      proportions in which mutations in these genes occur among AD patients in Israel
      has not been evaluated. To that end, we screened 52 Jewish-Israeli patients with
      AD: 22 with sporadic, early-onset disease (below 65 years), and 30 with FAD.
      Mutation screen employed denaturing gradient gel electrophoresis (DGGE) of exon
      specific PCRs and restriction enzyme digest. Five patients from three different
      families displayed mutations within the PS-1 gene: three patients of one family
      showed a mis-sense mutation in codon 120 (Glu 120Lys), and two other unrelated
      patients showed an identical mis-sense mutation in codon 318 (Glu318Gly). No
      patient showed an abnormal migration on DGGE (for APP) or mutant restriction
      digest pattern (for PS-2) genes. These data may indicate the existence of another
      familial Alzheimer disease (FAD) gene locus in the Israeli Jewish population.

PMID- 9781064
TI  - Screening of CFTR mutations in an isolated population: identification of carriers
      and patients.
AB  - One important application of the identification of disease-causing mutations is
      carrier screening in the general population. Such a project requires a simple
      accurate test by which a large proportion of the mutations can be identified.
      This study describes screening for CFTR mutations in an isolated Israeli Arab
      village. Two mutations, G85E and delta F508, accounted for all the CF alleles of
      these patients. The screening program tested for these two mutations, as well as
      the 5T allele, which has recently been shown to down-regulate the CFTR expression
      and cause variable phenotype. The screened population comprised 497 students from
      one school, which all the children of the village attend. The results revealed
      high carrier frequency, 8.5%, for the two CFTR mutations, G85E and delta F508,
      and a carrier frequency of 12% for the 5T allele. Two compound heterozygotes for
      the CFTR mutations, delta F508/G85E and G85E/5T, were identified. Both of these
      students had not been diagnosed previously as having CF since their disease
      presentation was not typical of CF. The CF incidence in this village was found to
      be extremely high, 1:72 life births. The screening results were reported to the
      physicians of the village to be used, upon request, for genetic counselling. This
      study emphasizes the importance of such programs for the identification of non
      classical patients and for carrier detection.

PMID- 9781066
TI  - [Neurology meeting of the French language. Paris 1-4 April 1998. Abstracts].

PMID- 9781065
TI  - Lower frequency of Gaucher disease carriers among Tay-Sachs disease carriers.
AB  - The heterozygote frequency of Gaucher disease (GD) and Tay-Sachs disease (TSD) is
      distinctly high among Ashkenazi Jews (1:29 for TSD and 1:16 for GD). Two main
      theories have been suggested to explain this high occurrence: a founder effect
      with subsequent genetic drift, and a selective advantage of heterozygotes. We
      compared the frequency of the GD most common mutation (1226A-->G) among carriers
      of the common TSD mutation (+1277 TATC) with the frequency of this mutation in
      the general Ashkenazi population. The frequency of GD carriers among 308 TSD
      heterozygotes was 1:28 which is about half the expected (P = 0.03). These results
      indicate that carriers of both diseases do not possess additional evolutionary
      advantage over single mutation carriers. A reasonable interpretation of these
      findings is that one or both mutations have arisen relatively recently in
      different regions of Europe and have not yet reached genetic equilibrium.

PMID- 9781067
TI  - [Is interleukin 2 useful in oncology?].

PMID- 9781068
TI  - [Progression of chronic renal insufficiency].

PMID- 9781069
TI  - [Infectious diseases in the works of Ismail Kadare].

PMID- 9781070
TI  - [Malaria, a worldwide scourge].
AB  - Malaria, mostly caused by Plasmodium falciparum, continues to take its toll
      throughout the world's tropical zone. The last report of the World Health
      Organization indicates renewed activity of this endemic disease, with 300 to 500
      million cases per year per 2.3 billion persons at risk, and 1.5 to 2.7 million
      death. Africa is the most affected, with an estimated incidence of 700 cases per
      1000, while in South America and Asia, the incidence varies around 4 to 5 cases
      per 1000. Using treated mosquito nets will probably not lower transmission
      sufficiently to decrease mortality. Early treatment, particularly in the child,
      is as important and combating transmission.

PMID- 9781071
TI  - [Human transmission and plasmodium resistance].
AB  - There is no longer malaria transmission in Europe and North America, while the
      transmission decreases in sub-tropical areas and increases in tropical countries.
      Most of malarias are now due to Plasmodium falciparum and happen in Africa. In
      the regions where the transmission is high, malaria is stable, baby mortality is
      high, and protective immunity is achieved in early childhood. Falciparum
      resistant malaria originates from mutations on drug target decreasing affinity to
      antifols, or mutations preventing accumulation of chloroquine in parasitized red
      blood cells. Resistance is a rapid event following large use of antifols, even
      associated, while falciparum chloroquine resistance is now widespread. Resistance
      to quinine, mefloquine and halofantrine is still at low levels out of Thailand,
      as their use remains through medical hands. Non resistance was observed yet with
      artemisinin derivatives.

PMID- 9781072
TI  - [Malaria in airports and their neighborhoods].
AB  - Though very rare compared to imported malaria, airport malaria should not be
      disregarded considering its very special gravity often due to late diagnosis. In
      most cases, it could be avoided if airlines and airports applied disinsecting
      measures vigilantly.

PMID- 9781074
TI  - [Severe malaria].
AB  - Falciparum malaria remains a major killer in developing countries, particularly
      for African children. The sequestration of parasitized erythrocytes in the deep
      microvasculature is mostly mediated by their cytoadherence to activated
      endothelium. Proinflammatory cytokines and particularly tumor necrosis factor
      contribute to severe disease but the pathophysiology of coma remains poorly
      understood. In young children, features of severe malaria include severe anemia,
      hypoglycemia and cerebral malaria. Half of the children with neurological
      impairment actually have raised intracranial pressure, and seizures are extremely
      common. Clinical respiratory distress usually reflects severe lactic acidosis. In
      non immune adults, pictures of severe sepsis with shock, acute renal failure and
      respiratory distress syndrome are common and often associated with bacterial
      coinfection. Although chemotherapy of malaria is challenged by the continuing
      evolution of antimalarial resistance, quinine remains the first-line drug for
      severe disease. The optimization of symptomatic management of severe malaria
      remains a major concern in developing countries.

PMID- 9781073
TI  - [Simple malaria attack].
AB  - The clinical presentation of malaria is, in most of cases, a malaria attack. It
      occurs in 90% of imported cases in France within 30 days after return of endemic
      area. Characteristic malaria paroxism have three stages: chills, high fever (> 39
      degrees C) and sweating stage. In this typical form, parasitaemia is easily
      disclosed. With the increasing spread of chemoresistance P. falciparum strains,
      many patients experience non specific symptoms before the onset of paroxysm,
      often complaining of malaise, headaches, myalgias and anorexia. In some cases
      temperature did not exceed 38 degrees C and physical examination revealed
      sometimes liver or splenic enlargement. These atypical presentations can
      masquerade other diseases such as a viral illness. In those patients blood smears
      were often negative and malaria diagnosis is carried out only by QBC or parasight
      test. Treatment of malaria attack needs antimalarial drugs effective against
      chemoresistant P. falciparum strains. Mefloquine of halofantrine can be delivered
      with the respect of guidelines prescription, given major side effects observed
      with these drugs (neuropsychiatric disorders with mefloquine and cardiac
      arrhythmias with halofantrine). Oral quinine sulfate can be used when the above
      drugs are not allowed.

PMID- 9781075
TI  - [Malaria prophylaxis].
AB  - Malaria, occurring in 1 to 2% of unprotected travellers to sub-Saharian Africa,
      remains a real risk because of its potential severity. In Asia or Latin America,
      the risk appears to be much lower, and in some cases, prevention can be limited
      to measures to avoid mosquito bites. Chemoprophylaxis by chloroquine-proguanil,
      mefloquine or, less frequently cyclines, is efficacious but poor compliance and
      frequent adverse events limits its interest. No regimen is totally effective and
      malaria must be considered in any traveller coming back from an endemic area with
      fever, even still receiving an appropriate prophylaxis.

PMID- 9781076
TI  - [New antimalarial drugs].
AB  - Resistance of Plasmodia to available antimalarials is becoming very frequent.
      Discovering new drugs in this field is therefore a health priority. Only two new
      antimalarials appeared in the last few years: artemether IM (Paluther) for the
      treatment of severe malaria and a chloroquine-proguanil combination (Savarine)
      for the malarial chemoprophylaxis. Several other new molecules are under
      investigation. Only a few of them result from a targeted pharmacological
      research. On the other hand, the clinical and biological evaluation of new
      antimalarials is often conducted without respect of the international industrial
      guidelines and will probably fail to offer all the guarantees of efficacy and
      safety required for registration in western countries.

PMID- 9781077
TI  - [Antimalarial vaccination: advances and controversies].
AB  - Since 1993 the new worldwide position of WHO is to encourage the development of
      an anti-malaria vaccine. The antigenic complexity of the parasite makes such
      development difficult. Twenty or more candidate molecules are being tested with
      different stages of development. They are directed against pre-erythrocyte or
      erythrocyte stages, or gametes, multivalent, or directed against the pathogenic
      metabolites of the parasite. Recent results have shown the interest of further
      study of the adjuvants. Controversy was crystallised by the disappointing results
      of the Pattaroyo vaccine, Spf66, which associates antigens of the sporozoite and
      the erythrocyte stage. These results nevertheless showed that vaccination against
      malaria is possible, but they underlined the undesirable effects of performing
      clinical studies too early or making premature recommendations.

PMID- 9781078
TI  - [...and then along comes standardized patients (II)].

PMID- 9781079
TI  - [Facial trauma].

PMID- 9781080
TI  - [Paget's bone disease].

PMID- 9781081
TI  - [Anemia].

PMID- 9781082
TI  - [Acute abdominal pain in children].

PMID- 9781083
TI  - [Respiratory distress of the newborn].

PMID- 9781084
TI  - [Mediastinal adenopathies and tumors].

PMID- 9781085
TI  - [Humoral immunity].

PMID- 9781086
TI  - [Accidental hypothermia].

PMID- 9781087
TI  - [Aminoglycosides: once a day?].

PMID- 9781088
TI  - [Aseptic femoral head osteonecrosis in the adult].

PMID- 9781089
TI  - [Abulcassis : the surgeon of Cordova].

PMID- 9781091
TI  - [Chronic abdominal pain in children].
AB  - Recurrent abdominal pain has been reported to occur in 10 to 15% of children
      between the ages of 5 and 15 years, and is considered to be one of the most
      encountered symptoms in childhood. It is important to avoid a shotgun approach to
      rule out all potential infectious, inflammatory, structural, and biochemical
      causes, that leads to an excess of diagnostic tests, as well as to avoid
      considering every abdominal pain as functional, which leads to a risk of
      misdiagnosing the rare organic causes of chronic abdominal pain. Careful history
      and clinical examination, completed if necessary by minimal laboratory
      investigation, allow either finding clues to the diagnosis of organic causes
      [represented most often by gastrointestinal diseases (constipation,
      gastroesophageal reflux) or nephro-urologic diseases] or suggesting that chronic
      abdominal pain may be of functional origin. Distinguishing between psychosomatic
      and functional chronic abdominal pain can be sometimes difficult.

PMID- 9781092
TI  - [Constipation in children].
AB  - Constipation in childhood is often unrecognized and diagnosed upon manifestations
      such as pain and pseudo-diarrhoea reflecting of a fecalith. It is sometimes
      complicated with urinary infection and can be a factor favouring enuresis. In the
      absence of deterioration in the general condition, it reflects modification of
      the propulsive functions of the colon or of the reservoir function of the rectum.
      In a such context, no further explorations are required. Treatment involves
      dietary recommendations such as good nutritional balance and sufficient fibre
      intake as well as mineral-based laxatives (paraffin oil) or nonabsorbable osmotic
      sugars. Enemas and suppositories should be used in case of stool withholding.
      Sphincter reeducation by biofeedback is indicated in child over 8 years of age
      after failure of medical therapy.

PMID- 9781094
TI  - [Food allergies and intolerances in children].
AB  - Allergies and food intolerance together comprise the manifestations of "adverse
      food reaction". The best known and most common are: allergy to cow's milk
      proteins (prevalence 0.5% to 7.5%), intolerance to lactose (prevalence after
      weaning 5 to 100%) and gluten intolerance (prevalence 0.5%). Treatment of these
      conditions is based on management of the diet by exclusion (or reduction) of the
      responsible food or antigen.

PMID- 9781093
TI  - [Diarrhea in children].
AB  - Diarrhea is a very common symptom in childhood. Most cases are acute, in relation
      with infectious agents. They resolve in few days, the main complication being
      acute dehydration. At the opposite, chronic diarrhea may be complicated by
      denutrition and failure to thrive. In most cases, the symptom is related to a
      chronic nonspecific diarrhea of childhood, without any nutritional consequence
      and the family will be reassured. Sometimes, clinical data suggest an organic
      etiology. In this case, additional investigations will be performed, taking into
      account the semiology of the diarrhea and the relative frequency of the different
      etiologies.

PMID- 9781095
TI  - [Gastroesophageal reflux in children].
AB  - Gastro-oesophageal reflux is a common disease in childhood, indicating either a
      variation from normal in the first months of life or a genuine disease in older
      infants or children. Digestive symptoms dominate in the young infant whereas
      respiratory ones should not be overlooked when the child grows. Diagnosis relies
      on history and clinical examination. (Esophageal pH-metry and/or upper endoscopy
      may be required. Most of the time, medical management appears sufficient.

PMID- 9781096
TI  - [Inflammatory bowel disease in children].
AB  - Pediatric Crohn's disease is a severe disease with digestive and extra-digestive
      manifestations. Growth retardation is a common feature. Diagnosis is based on
      endoscopy and histology with evidence of granulomas. Remission can be achieved by
      using anti-inflammatory treatment or continuous enteral feeding. Course of the
      disease is marked by relapse with extension. Surgery is limited in children.
      Ulcerative colitis is limited on rectum and colon and includes also extra
      digestive manifestations. Bloody diarrhoea with abdominal pain is characteristic.
      Diagnosis is based on endoscopy and histology. Treatment depends on the severity
      of the disease but can include rapidly colectomy for persistent severe bloody
      diarrhoea.

PMID- 9781097
TI  - [Gastrointestinal hemorrhages in children].
AB  - Gastrointestinal bleeding is not rare in paediatric practice. Always impressive
      to the surrounding family, they reveal an underlying affection (portal cavernous
      haemangioma, ulcer) or complicate a progressing disease (oesophagitis, varix).
      Gastrointestinal endoscopy should be made rapidly in a paediatric setting. The
      main causes are: before 2 years of age and over 7 years, peptic oesophagitis;
      from 2 to 7 years, acute lesions of the gastroduodenal mucous membrane and
      ulcers. Lower tract bleeding (melaena or rectal bleeding) is mainly due to anal
      fissures, polyps, severe inflammatory colitis and enterocolitis.

PMID- 9781098
TI  - [Pediatric proctology].
AB  - The approach to proctologic disorders has been little studied in the child. The
      region is, however, easily accessible for direct examination, and the predominant
      abnormalities are the rectal consequences of passing hard and/or voluminous
      stools that are often responsible for pain and bleeding. Other lesions are also
      observed (pseudo-haemorrhoidal vascular swelling, abscess, dermal scar
      proliferation, prolapsus) but are generally easily diagnosed and treated,
      although in a paediatric context.

PMID- 9781099
TI  - [Public health priorities].

PMID- 9781100
TI  - [Medical confidentiality].

PMID- 9781101
TI  - [Tobacco use disorder].

PMID- 9781102
TI  - [Mumps].

PMID- 9781103
TI  - [Epidermoid cancers and bronchial adenocarcinomas].

PMID- 9781104
TI  - [Hyperkalemia].

PMID- 9781105
TI  - [Acute nasal, sinus and pharyngeal infections in children].

PMID- 9781106
TI  - [Homeopathy: myth or reality?].

PMID- 9781107
TI  - [New biological monitoring of HIV infection].

PMID- 9781108
TI  - [The treatment of tetanus].

PMID- 9781109
TI  - [Epidemiology of infectious endocarditis].
AB  - The incidence of infective endocarditis (20 to 160 cases per million inhabitants
      yearly) increases with age; it does not seem to be decreasing over time. There is
      no previously known heart disease in 30% of the patients, a native valve disease
      in 30 to 60%, a prosthetic valve in 15-20%. Streptococci remain the leading
      microorganisms. Digestive streptococci and staphylococci are increasing.
      Iatrogenic portals of entry are in progression. During the hospital stay, case
      fatality ratio varies from 13 to 20%. After endocarditis, the patient remains at
      risk of late cardiac surgery and of recurrence. Survival after 5 years is
      approximately 85%.

PMID- 9781110
TI  - [The contribution of experimental models to the physiopathology and treatment of
      infectious endocarditis].
AB  - The model of experimental endocarditis can be used for the investigation of the
      different steps in the physiopathologic process leading to the formation of the
      infected cardiac vegetation. It has also greatly contributed to the knowledge of
      the characteristics of the infected vegetation. These data allow a better
      understanding of the therapeutic consequences (both preventive and curative) of
      the physiopathologic process.

PMID- 9781111
TI  - [Diagnostic criteria of infectious endocarditis].
AB  - Accurate diagnostic criteria for infective endocarditis are essential to
      epidemiological studies. The von Reyn's criteria have been widely used for more
      than a decade after they were published in 1981. In 1994, the Duke's criteria for
      the clinical diagnosis of infective endocarditis were published, incorporating
      echocardiographic findings. They are modeled after the Jones criteria for the
      identification of cases of rheumatic fever and include 2 major and 6 minor
      diagnostic criteria. They are about twice as specific as the former von Reyn's
      criteria, without loss of specificity, and should become a standard reference for
      diagnosing infective endocarditis.

PMID- 9781112
TI  - [The microbiology of infectious endocarditis].
AB  - If streptococci and staphylococci remain the main bacteria responsible for
      infective endocarditis (80%), the emergence of Streptococcus bovis associated
      with intestinal lesions, the confirmation of the role of Coxiella burnetii, and
      the discovery of the responsibility of Bartonella sp in case of negative blood
      culture endocarditis have been the principal microbiological modifications during
      the last few years. Blood cultures performed under the best technical conditions
      and the examination and culture of the valve after surgery remain the better
      means for diagnosing infective endocarditis. In case of negative blood culture
      (11% of the infective endocarditis), the serologic tests against C. burnetii and
      Bartonella should decrease the rate of diagnostic uncertainty. The development of
      bacteriological techniques, particularly molecular methods, should improve the
      microbiology of infective endocarditis lead to the discovery new aetiological
      agents.

PMID- 9781113
TI  - [Cardiac ultrasonography in the diagnosis and monitoring of infectious
      endocarditis].
AB  - Transthoracic and transoesophageal doppler echocardiography has become an
      essential tool for the diagnosis of infective endocarditis. It detects valvular
      vegetations and destructions, evaluates regurgitations, and appreciates
      haemodynamic tolerance. Recognition of endocarditis, early identification of high
      risk patients, and detection of mechanical complications are the most accurate
      informations derived from this technique. Transoesophageal echocardiography has
      the potential to avoid the difficulties encountered using the transthoracic
      approach, and it must be used particularly in the presence of non diagnostic
      transthoracic examination when clinical suspicion is high.

PMID- 9781114
TI  - [Methods and monitoring of antibiotic therapy of infectious endocarditis].
AB  - Antibiotic treatment of infective endocarditis has to be discussed when the
      microorganism has been identified. Antibiotics must be started as soon as
      possible, just after blood samplings in case of clinical bacteraemia, or as soon
      as blood cultures are positive. In case of negative blood cultures, diagnosis of
      endocarditis has to be reconsidered, according to Duke's criteria, and
      antibiotics must not be started until there is strong evidence in favour of
      infective endocarditis. Antibiotic treatment must be bactericidal, intravenously
      administered, for a long time to sterilize vegetations. Duration of antibiotics
      depends on the microorganism, and whether there is a valvular prosthesis or not.
      Hospitalization is often mandatory, but there is a trend towards the use of
      outpatient treatments, only possible in some indications.

PMID- 9781115
TI  - [Prevention of infectious endocarditis].
AB  - Although prophylaxis with antibiotics cannot avoid all cases of infectious
      endocarditis, it remains the main approach capable of reducing the frequency of
      this severe disease. It consists in using an adapted antibiotic cover in
      situations exposing to bacteraemia in patients at-risk with known cardiopathy. In
      France, recommendations have been established by a consensus conference in 1992.
      The fact that the incidence of this infection has not decreased merits recalling
      these recommendations.

PMID- 9781116
TI  - [Surgery of infectious endocarditis].
AB  - Thirty to fifty percent of patients with infective endocarditis are operated on
      during the active phase of the disease; this percentage is higher in case of some
      valvular localizations (aortic), in case of early prosthetic valve endocarditis,
      in case of some microorganisms (Staphylococcus aureus, gram-negative, fungus,
      intracellular microorganism). Operative death (at 30 days) is below 10% in native
      valve endocarditis, close to 50% in early prosthetic valve endocarditis, and
      below 20% in late prosthetic valve endocarditis. When active infective disease
      has been healed by medical treatment alone, half the patients need surgery in the
      first 2 years of follow-up; the indications for surgery are the functional
      status, the degree of valvular leaks and other lesions, the degree of ventricular
      dilatation.

PMID- 9781117
TI  - [Evidence-based medicine 1998 (I)].

PMID- 9781118
TI  - [Parotid tumors. Diagnostic orientation].

PMID- 9781120
TI  - [Rheumatoid purpura in children and adults. Diagnosis, prognosis].

PMID- 9781119
TI  - [Vaccinations. Immunologic and microbiologic principles, indications,
      contraindications, accidents, efficacy (schedule and compulsory aspects of
      vaccination excluded)].

PMID- 9781121
TI  - [Blood transfusion and blood-derived products transfusion. Immunologic principles
      and indications].

PMID- 9781122
TI  - [Acute osteo-articular infection of the limbs of children. Physiopathology,
      diagnosis, progression, prognosis, treatment].

PMID- 9781123
TI  - [Acute appendicitis and its complications. Diagnosis, treatment].

PMID- 9781124
TI  - [Duchenne muscular dystrophy. Fragile X syndrome. Epidemiology, genetics,
      diagnosis].

PMID- 9781125
TI  - [The threat of premature delivery. Etiology, diagnosis, principle of treatment].

PMID- 9781126
TI  - [Are antibiotics over-consumed+?].

PMID- 9781127
TI  - [Congenital myasthenic syndromes].

PMID- 9781128
TI  - [Zola's medical ideas].

PMID- 9781129
TI  - [Biopathology of disseminated lupus erythematosus].
AB  - Systemic lupus erythematosus is associated with a plethora of immunological
      abnormalities. First, there are antinuclear autoantibodies directed towards
      insoluble (mainly desoxyribonucleic acid, histones and nucleosomes) or soluble
      nuclear components (mainly Sm, RNP and Ro/SSA particles). There are then
      autoantibodies other than antinuclear, recognizing cells (erythrocytes,
      lymphocytes, neutrophils, endothelial cells), organelles (Golgi apparatus,
      ribosomes) or molecules (cardiolipids, C1q, stress proteins). Finally, there are
      immunological abnormalities other than autoantibodies, such as immune complexes,
      monoclonal immunoglobulins or complement variations. In fact the pathogenetic
      role of these perturbations remains a matter for speculation.

PMID- 9781131
TI  - [Dermatologic manifestations of lupus].
AB  - Cutaneous manifestations of lupus include lupus lesions, vascular lesions and non
      lupus and non-vascular lesions. Differences in clinical appearance, pathological
      findings and duration of clinical activity lead to subdivide lupus lesions into
      three major subsets: acute, subacute and chronic. All may be observed in systemic
      lupus erythematosus with a highly variable frequency depending upon the subset.
      Cutaneous lesions are initially treated with antimalarials. Vascular lesions may
      be produced by an inflammatory process with vasculitis, or by a thrombotic
      process often associated with antiphospholipid antibodies. Except for alopecia,
      the non-lupus and non-vascular lesions are rarely observed.

PMID- 9781130
TI  - [Definition, diagnosis, and classification of lupus].
AB  - Polysystemic lupus erythematosus is a disease of unclear origin. Spontaneous
      course is characterized by flares followed by remissions. The classification
      criteria are often used as diagnostic criteria, but they are insensitive for
      early diagnosis purpose. Decisional trees and ponderation of the various criteria
      have been reported to help clinicians for early diagnosis. Clinical variants of
      lupus erythematosus are numerous such as initial clinical manifestations;
      epidemiological considerations have shown different subsets with different
      manifestations depending on ethnicity, age at first symptoms, environmental
      factors (drug-induced lupus). Genetic background influences the autoantibody
      profile. Correlations have been reported between serological and clinical
      presentation.

PMID- 9781132
TI  - [Severe visceral involvement of lupus].
AB  - During the past few years, changes in the spectrum of serious forms of systemic
      lupus erythematosus have been observed, and generally, the prognosis has
      improved. This results from a better understanding of the mechanisms of some
      visceral involvements (especially cerebral and cardiovascular), from the
      characterization of the antiphospholipid antibodies syndrome, and from a better
      management. As a result, kidney and central nervous system involvements are not
      the main causes of mortality any more. However, increasing survival leads to a
      higher frequency of some late complications, especially related to
      atherosclerosis.

PMID- 9781133
TI  - [Antiphospholipid antibodies syndrome].
AB  - Antiphospholipid syndrome is characterized by thromboses, fetal losses and
      antiphospholipid antibodies. This group of antibodies includes lupus
      anticoagulant, false positive syphilitic reaction, anionic (such as
      anticardiolipin) and neutral phospholipids antibodies, and anti
      phospholipid/cofactors antibodies (such as anti-beta 2-glycoprotein 1). Dominant
      manifestations are recurrent thrombophlebitis and pulmonary embolism, arterial
      occlusive disease of young people, obstetrical complications such as fetal
      losses, livedo, and thrombocytopenia. Warfarin is presently the main treatment.

PMID- 9781134
TI  - [Pregnancy and acute disseminated lupus erythematosus].
AB  - Until recently, pregnancy was thought to induce lupus flares; pregnancy was
      contraindicated and therapeutic abortion was recommended. Such concepts are now
      subjected to debate and successful outcome of pregnancy can be expected when
      lupus has not been active for several months, and with a successful partnership
      between specialists in high-risk obstetrics and in rheumatology or internal
      medicine.

PMID- 9781136
TI  - [Treatment of systemic lupus erythematosus systemic].
AB  - Patients with systemic lupus erythematosus require adequate information (sun
      avoidance, fair compliance, smoking discontinuation, adequate contraception and
      diet, pregnancy planning). Nonsteroidal antiinflammatory drugs and antimalarials
      are effective in patients presenting with skin and articular involvement.
      Visceral lesions and hemocytopenias require the use of steroids, alone or in
      association with immunosuppressive agents. Long-term anticoagulation with an INR
      of 3-3.5 achieves the prevention of recurrent thrombotic events. Experimental
      data suggest that more specific treatments and even regimens aimed at eradication
      of human lupus might soon arise.

PMID- 9781135
TI  - [Infections and lupus].
AB  - Infections are one of the major causes of morbidity and mortality during the
      course of systemic lupus erythematosus, and are promoted by various dysfunctions
      of the immune system, some of which are poorly understood. Other predisposing
      factors have been also identified such as the presence of glomerulonephritis and
      a treatment with high-dose corticosteroids or immunosuppressors. These factors
      have been particularly associated with the occurrence of opportunistic infections
      such as systemic candidiasis or Pneumocystis carinii pneumonia, whose frequency
      has increased with the intensity of therapeutic strategies. The most frequent
      infections encountered are induced by community-acquired microorganisms. Thus,
      initiating an empirical antibiotic treatment is justified in febrile patients
      with lupus erythematosus. In case of marked lymphopenia, it is recommended to
      start cotrimoxazole as primary prophylaxis against P. carinii pneumonia.

PMID- 9781138
TI  - [Diffused goiter and thyroid nodule. Diagnostic indications].

PMID- 9781137
TI  - [Evidence-based medicine 1998 (II)].

PMID- 9781139
TI  - [Hemophilia. Diagnosis, genetics, complications].

PMID- 9781140
TI  - [Bacterial cutaneous infections: impetigo, furuncle, erysipelas. Etiology,
      diagnosis, evolution, treatment].

PMID- 9781141
TI  - [Cancer of the rhinopharynx and the oropharynx. Epidemiology, diagnosis,
      complications a long time after treatment].

PMID- 9781142
TI  - [Malaise, syncope and short loss of consciousness. Diagnostic indications].

PMID- 9781143
TI  - [Clinical trials. Methodological principles and ethical aspects in the evaluation
      of therapies].

PMID- 9781144
TI  - [Neurotic syndrome: phobic neurosis. Diagnosis, treatment].

PMID- 9781145
TI  - [Lumbago. Diagnostic indications].

PMID- 9781147
TI  - [The bursa of Fabricius. It gives wings to immunology].

PMID- 9781146
TI  - [Treatment of Crohn's disease with anti-TNF alpha].

PMID- 9781148
TI  - [Histopathological diagnosis of Hodgkin's disease].
AB  - The diagnosis of Hodgkin's disease is based on histopathologic examination and
      the demonstration of Reed-Sternberg cells. These cells express antigens (Ki
      1/CD30 CD15) which are of diagnostic value. Two types of Hodgkin's disease are
      now identified: 1. the "classical Hodgkin's disease" which includes nodular
      sclerosis, mixed cellularity and some tumors rich in malignant cells formerly
      designated Hodgkin's disease with lymphocyte depletion; 2. the "lymphocyte
      predominance Hodgkin's disease" in particular the nodular form (paragranuloma).
      These lesions are now considered an indolent form of B-cell lymphoma with
      possible transformation into large B-cell lymphoma. Epstein-Barr virus is
      involved in the "Classical Hodgkin's disease" but not in the "Lymphocyte
      predominance Hodgkin's disease". However, the role of Epstein-Barr virus in the
      occurrence of the disease and the prognostic implications of its detection remain
      ro be elucidated.

PMID- 9781149
TI  - [Physiopathology of Hodgkin's disease].
AB  - Reed-Sternberg cell, the neoplastic component of Hodgkin's disease, still remains
      "intriguante". Despite contreversies, there is more and more evidence for a
      lymphoid B cell origin of Hodgkin's disease. The role of Epstein-Barr virus,
      cytokines and (or) oncogenes expression in the pathogeny can be suggested,
      although the precise mechanisms leading to transformation and (or) accounting for
      tumour progression are still elusive. Advances in the biology of Hodgkin's
      disease have led to the distinction between two entities, "classical" Hodgkin's
      disease and Poppema's paragranuloma, with different clinical aspects. The
      definition of diagnostic criteria has been also helpful to separate Hodgkin's
      disease from other lymphomas mimicking Hodgkin's disease such as anaplastic large
      cell lymphomas?

PMID- 9781150
TI  - [Staging of Hodgkins's disease].
AB  - Initial staging of Hodgkin's disease must be extensive to define all initially
      involved sites. It includes a physical examination to look for peripheral lymph
      nodes. Chest X rays and CT scan are mandatory to explore deep lymph nodes and
      extranodal sites (e.g., lung, liver...). Biological tests look for an
      inflammatory syndrome. After this initial staging the disease is classified
      according to the dissemination of lymph nodes and to the presence of extranodal
      involvement. We take also in account the evolutive symptoms and the erythrocyte
      sedimentation rate. The staging helps for therapeutic options and must be
      performed after treatment to evaluate therapeutic results and search for a
      residual mass.

PMID- 9781151
TI  - [Prognostic factors and treatment of localized Hodgkin's disease].
AB  - Cure is warranted in most cases of localized Hodgkin's disease, the more frequent
      ones. However, after 10 years of follow-up, early and late mortality of
      iatrogenic origin exceed casualties related to tumor progression. Reductions in
      irradiation doses and fields, as well as wiser chemotherapy choices attempt to
      circumvent these complications. Nevertheless, as long as the mechanism of disease
      propagation and the prognostic factors are not better defined, only pragmatic
      approaches are being tested. Large cooperative trials are therefore needed to
      improve the outcome.

PMID- 9781152
TI  - [Prognostic factors and treatment of advanced Hodgkin's disease].
AB  - Treatment strategy is based on prognosis groups although there is no consensus on
      their definition. In stages IIIA with unfavorable factors and stages IIIB or IV
      without high risk factors, chemotherapy alone or followed by irradiation is used.
      To reduce toxicity, radiation therapy on bulky disease and residual masses is
      preferred to extended fields. Indications for intensive chemotherapy with
      autograft of hematopoietic stem cells as initial treatment for high-risk patients
      must be determined with therapeutic trials.

PMID- 9781154
TI  - [Late treatment related complications of Hodgkin's disease].
AB  - Patients cured of Hodgkin's disease are at high risk for developing late
      treatment-related complications. Radiation therapy is responsible for non
      malignant complications such as pulmonary, digestive, thyroid and cardiac
      toxicity. Chemotherapy is mainly responsible for pulmonary toxicity and gonadal
      dysfunction in females and in males, whatever the age at treatment. Hodgkin's
      disease therapy may also result in secondary malignancy which is considered the
      most serious complication. White the use of non leukaemogenic chemotherapy can
      limit the incidence of secondary leukaemia, that of secondary solid tumours is
      still increasing, being 15% after 20 years. Altogether, malignant and non
      malignant complications are still responsible for a non negligible overmortality.

PMID- 9781153
TI  - [Treatment of resistant forms and recurrence of Hodgkin's disease].
AB  - In Hodgkin's disease, cases of resistance to initial treatment and of recurrence
      have a low probability of cure. Remission of less than one year and disseminated
      stage are the two main prognostic factors. In favourable cases (late recurrence
      or localised stage), conventional chemotherapy, associated or not with
      radiotherapy, can be suggested. In case of early relapse or disseminated stage,
      intensified treatment followed by autografting of hematopoietic line cells should
      be considered. In highly unfavourable cases associating early relapse and
      dissemination, to which refractory cases can be added, new therapeutic strategies
      should be evaluated in prospective studies.

PMID- 9781155
TI  - [Period of probation compared to ambulatory practice experience (II): opinions of
      students and teachers].

PMID- 9781156
TI  - [Genital prolapse. Diagnosis].

PMID- 9781157
TI  - [Anaerobic bacteria soft tissue infection. Etiology, diagnosis, treatment].

PMID- 9781158
TI  - [Adrenergic beta agonists (adrenaline, dopamine, dobutamine, salbutamol); beta
      blockers. Fundamentals and rules of use].

PMID- 9781159
TI  - [State of agitation. Diagnostic guidance and procedures in emergencies along with
      drug dosage recommendations].

PMID- 9781160
TI  - [Newborn infant bacterial infections. Diagnosis, treatment principles,
      prevention].

PMID- 9781161
TI  - [Thrombolytics. Fundamentals and rules of use].

PMID- 9781162
TI  - [Thrombocytosis. Diagnostic guidance].

PMID- 9781163
TI  - [Mitral valve stenosis. Physiopathology, diagnosis].

PMID- 9781164
TI  - [Dysphonia. Diagnostic guidance].

PMID- 9781165
TI  - [Postpartum hemorrhage. Diagnosis and treatment fundamentals].

PMID- 9781166
TI  - -Medical management of severe acute colitis-.

PMID- 9781167
TI  - [History of hospital personnel clothing. The case of the Public Assistance of
      Paris].

PMID- 9781168
TI  - [Calciotropic hormones and integrated regulation of calcemia and calcium
      balance].
AB  - Calcium homeostasis is regulated by fluxes occurring at the levels of bone,
      kidney and intestine, fluxes which are controlled by calciotropic hormones. Bone
      resorption is stimulated by parathyroid hormone and by the bioactive metabolite
      of vitamin D, 1,25-dihydroxyvitamin D, or calcitriol. The renal tubular capacity
      to reabsorb calcium is regulated by parathyroid hormone, and calcium intestinal
      absorption is increased by calcitriol. Any modification of extracellular calcium
      concentration triggers a series of hormonal homeostatic reactions, aimed at
      changing these fluxes and correcting thereby calcium homeostasis perturbations.
      The evaluation of these fluxes provides information on the pathophysiological
      mechanism(s) implicated. Then the determination of calciotropic hormones
      circulating levels allows one the confirmation of the diagnosis evoked.

PMID- 9781169
TI  - [Bone remodeling: evaluation methods].
AB  - Bone tissue undergoes continual renewal in order to keep the mechanical
      competence of the bone matrix. This is performed by two cells: osteoclasts which
      resorb the calcified matrix and osteoblast which synthetize a new bone matrix.
      Biochemical markers of bone remodelling allow the evaluation of the activity of
      each type of bone cells. An unbalance in this process induces modifications of
      the amount of calcified tissue and of the bone microarchitecture. Several
      technics based on X-ray and ultrasound allow a non invasive evaluation of these
      modifications.

PMID- 9781170
TI  - [Primary hyperparathyroidism].
AB  - Primary hyperparathyroidism was initially regarded as a rare and severe disease.
      In recent years, introduction of routine screening of serum calcium has
      contributed to a dramatic increased rate of detection of primary
      hyperparathyroidism in the population, and asymptomatic forms of this disease are
      now the rule. Surgery remains the only curative treatment. However a medical
      follow-up may be justified in asymptomatic patients whose serum calcium levels
      are only midly elevated and whose renal and bone status are close to normal. The
      medical follow-up is considered to be safe only with conscientious long-term
      monitoring. Surgery becomes mandatory if the follow-up shows worsening
      hypercalcemia, bone deterioration, renal impairment, calcium stone, or increased
      hypercalciuria.

PMID- 9781171
TI  - [Extraparathyroid hypercalcemia].
AB  - Hypercalcemia is the consequence of increased calcium fluxes into extracellular
      fluid. The origin of calcium is bone resorption, renal tubular reabsorption,
      rarely intestinal absorption. Among inpatients, the most frequent cause of
      hypercalcemia is tumor, with pathophysiological mechanisms implicating both
      enhanced bone resorption and increased renal tubular reabsorption of calcium. The
      presence of hyperosteolysis in most patients with hypercalcemia of non
      parathyroid origin, constitutes the rationale for the use of potent bone
      resorption inhibitors, such as bisphosphonates, in the acute treatment of
      hypercalcemia.

PMID- 9781172
TI  - [Hypocalcemia].
AB  - Hypocalcemia may be presently defined as a serum calcium value below the
      reference range, usually below 8,4 mg/dL, in neonates as well as adults. This
      alteration may remain asymptomatic or be associated with severe clinical
      disorders. Its causes include classical pathologies such as vitamin D deficiency,
      hereditary or acquired resistances to vitamin D, hypomagnesemia,
      hypoparathyroidisms and resistances to parathyroid hormone, renal insufficiency
      and massive cellular lysis. They also include iatrogenic causes as well as
      recently isolated diseases, like the hypocalcemic syndrome due to mutations in
      the calcium-sensing receptor gene. The management of hypocalcemia depends on its
      causes, clinical consequences, severity, and on the age of the patient.

PMID- 9781173
TI  - [Anomalies of phosphate and calcium metabolism in chronic renal insufficiency].
AB  - The disturbances of calcium and phosphate metabolism in chronic renal failure
      involve mainly two hormones, namely calcitriol and parathyroid hormone. They are
      thought to start with a reduction in calcitriol synthesis, probably due to
      several mechanisms, and with a reduced action of calcitriol at its target
      tissues, including the parathyroid cell. They may lead to several complications
      of clinical importance including both secondary hyperparathyroidism, in the
      presence or absence of vitamin D deficiency, and hypoparathyroidism. The
      corresponding expression at the bone level may be osteitis fibrosa, osteomalacia
      or adynamic bone disease. These complications are frequently associated with soft
      tissue calcifications, mainly vascular and periarticular, with serious clinical
      consequences in some patients.

PMID- 9781174
TI  - [Hypercalciuria].
AB  - Hypercalciuria is a very frequent disorder that is defined by a daily calcium
      excretion rate in excess of 0.1 mmol/kg. Whatever its mechanism, it always
      expresses an increased input of calcium in extracellular fluid, from intestine
      and (or) bone. In few instances, hypercalciuria is secondary to an underlying
      disease that needs to be identified (primary hyperparathyroidism, cancer,
      granulomatosis...). However, in most cases, it is a primary (idiopathic) disorder
      that reveals an abnormal handling of calcium by intestinal and renal tubular
      epithelia. It is then treated by a restricted dietary supply in sodium and animal
      proteins, and by the use of thiazide diuretics.

PMID- 9781175
TI  - [Regulation of phosphatemia and hypophosphatemia].
AB  - Phosphate is an essential element for cellular metabolism and bone
      mineralization. The kidney regulates phosphate homeostasis by modulating the
      proximal reabsorption of phosphate. This regulation is mediated by hormonal or
      autocrine/paracrine factors. Recent results concerning the molecular structure of
      phosphate transport systems have clarified the mechanisms underlying the effects
      of these mediators. Hypophosphatemia is a frequent biological finding which
      results either from an intracellular shift of phosphate, or from a defect in the
      intestinal absorption or a renal leak. The decrease in phosphate leads to a
      depletion in cellular ATP (which accounts for neurological and muscular
      symptoms), to bone demineralization and to renal lithiasis when a renal leak
      exists.

PMID- 9781176
TI  - [Disease management].

PMID- 9781178
TI  - [Hemoptysis: diagnostic direction].

PMID- 9781177
TI  - [Prenatal protection. Regulations. Perinatal mortality. Epidemiology].

PMID- 9781179
TI  - [Hip pain: diagnostic direction].

PMID- 9781180
TI  - [Adult epilepsy. Etiology, diagnosis, prognosis, treatment].

PMID- 9781182
TI  - [Myocardial infarct. Epidemiology, physiopathology, diagnosis, evolution,
      complications, treatment].

PMID- 9781181
TI  - [Acute poisoning by barbiturates, tranquilizers, tricyclics, paracetamol,
      salicylates. Diagnosis, treatment].

PMID- 9781183
TI  - [Primary prevention of coronary disease with drugs].

PMID- 9781185
TI  - [The birth of hospital bacteriology].

PMID- 9781186
TI  - [Asbestos-related diseases].
AB  - The growing use of asbestos in France like in other industrialized countries
      since the beginning of the century is the reason of the increase of asbestos
      related diseases, which occur after long latency periods. From asymptomatic
      benign pleural plaques up to malignant mesothelioma of poor prognosis, the
      fibrogenic and carcinogenic properties of asbestos mainly concern occupationally
      exposed subjects. The Institut national de la sante et de la recherche medicale
      (INSERM) expert committee concluded that about 1,950 deaths due to asbestos
      related cancers occurred in France in 1996. Reinforcement of French legislation
      aims at reducing all kinds of asbestos exposure.

PMID- 9781188
TI  - [Health effects of artificial mineral fibers].
AB  - Data from mortality studies in cohorts of workers employed in the production of
      man-made mineral fibres, where levels of exposure were generally low, show an
      excess of mortality by lung cancer, although the role of the fibres themselves
      remains unclear in this excess. Standardized mortality ratio for lung cancer was
      lower in glass-wool production workers than in rock-slag-wool workers.
      Preliminary data for refractory ceramic fibres-exposed workers suggest the
      occurrence of benign pleural diseases and obstructive functional defects.
      Attention should be paid to levels of exposure to various man-made mineral fibres
      encountered by end-users commonly exposed to peaks of fibre concentrations higher
      than production workers.

PMID- 9781187
TI  - [Risk and clinical surveillance of workers exposed to asbestos].
AB  - The role of the family doctor in the medical surveillance of asbestos-exposed
      workers is important, mainly after retirement. The surveillance modalities should
      take into account the levels of exposure and the date of the beginning of
      exposure (long latency period of asbestos-related diseases). Due to the lack of
      evidence of improvement of lung cancer prognosis, and in the absence of effective
      treatment of mesothelioma, the interest of medical surveillance is at the present
      time medico-legal rather than strictly medical. Consequently, maximalist
      attitudes, costly and may be hazardous, should be avoided.

PMID- 9781189
TI  - [Occupational asthma].
AB  - Occupational asthma is specifically induced by repeated exposure to substances in
      the work place. Diagnosis requires using the results of numerous tests, and a
      challenge test is the most appropriate to establish the diagnosis of occupational
      asthma due to chemical agents. Agents responsible for occupational asthma may be
      of animal or vegetable origin, or may be chemical agents. The pathophysiological
      mechanisms of occupational asthma are not well known. It is probable that
      immunologic mechanisms play an important role, in particular in occupational
      asthma due to glycoproteins. An important feature of occupational asthma is the
      relationship to chemical substances, for which the mechanisms are often still
      hypothetical. From the legal viewpoint, a recent law holds the promise of better
      compensation for those who are afflicted.

PMID- 9781190
TI  - [Respiratory pathology in the agricultural environment].
AB  - Farmers are usually exposed to a wide variety of noxious organic or chemical
      substances. This explains why agriculture is probably one of the occupations
      where prevalences of respiratory diseases are the highest. Some diseases such as
      extrinsic allergic alveolitis, allergic asthma, silo filler's disease or
      pesticides-related fibrosis are classic and well described. Others, more recently
      identified although probably more frequent, remain often unrecognized. This is
      notably the case of agricultural chronic bronchitis and of organic dust toxic
      syndrome. Sometimes, these respiratory pathologies are intricate and lead to a
      complex presentation where signs of irritation or inflammation of the respiratory
      tract, bronchial hyperreactivity and chronic bronchial obstruction are mixed.

PMID- 9781191
TI  - [Acute toxic pneumopathies].
AB  - The nature and extent of the acute injury due to toxic inhalants depend on the
      inhalant's solubility in water pH and chemical reactivity, on the aerodynamic
      diameter of particles (when the inhalant is an aerosol), and on the degree of
      exposure. Initial signs and symptoms indicate upper airways and bronchial
      irritation. Laryngeal oedema and (or) severe bronchospasm may be rapidly lethal.
      After cessation of exposure a transient improvement is generally observed;
      however a delayed pulmonary oedema may occur within the first 48 hours. On the
      following days, bacterial surinfection is a common complication. Possible long
      term sequelae are reactive airways dysfunction syndrome and bronchiolitis
      obliterans.

PMID- 9781192
TI  - [Yesterday's and today's pneumoconiosis].
AB  - Pneumoconioses are still a frequent cause of interstitial lung disease, that can
      be lethal. Nevertheless, the improvement of working conditions has led to a lower
      incidence of severe forms of disease. More sensitive diagnostic techniques, such
      as high resolution computed tomography scan, are used in early diagnosis and in
      the medico-legal expertise. Immunological techniques and mineralogical analyses
      of biological samples allow a more rigorous work-up in these cases. In this
      regard, bronchoalveolar lavage can bring very interesting information from the
      cellular, immunological, and mineralogical points of view.

PMID- 9781193
TI  - [Claim, recognition, compensation of occupational respiratory diseases].
AB  - Many occupations involve an environment that may provoke lung diseases. This
      should be kept in mind whenever lung disease is diagnosed for detection of an
      occupational factor requires steps toward prevention, and compensation may be due
      the patient. Counselling the patient on the administrative steps to be taken
      often requires the advice of the occupational physician, the consultant physician
      or specialised services in order to maintain the rights of the patient.

PMID- 9781195
TI  - [Acute nephrotic syndrome. Physiopathology, diagnosis].

PMID- 9781196
TI  - [Systems of hospital (public and private) and ambulatory care. Structures and
      principles of rating].

PMID- 9781197
TI  - [Hyperlipoproteinemias. Epidemiology, etiology, physiopathology, diagnosis,
      treatment].

PMID- 9781198
TI  - [Heparins, antivitamins K. Principles and rules for their use. Dosage of non
      fractionated heparins].

PMID- 9781199
TI  - [Cataract. Etiology, diagnosis, treatment principles].

PMID- 9781200
TI  - [Limited mouth opening. Diagnostic indications].

PMID- 9781201
TI  - [Hyperthyroidism. Etiology, physiopathology, diagnosis, evolution, treatment].

PMID- 9781202
TI  - [Trigeminal neuralgia. Diagnosis].

PMID- 9781203
TI  - [From gene transfer to gene therapy in cystic fibrosis, how long is the road?].

PMID- 9781204
TI  - [Hemorrhagic fever with renal syndrome].

PMID- 9781205
TI  - [Radiocinematography and intestinal peristalsis].

PMID- 9781206
TI  - [Breast cancer: epidemiology, risk factors, screening].
AB  - Breast cancer is the most frequent cancer in women: more than 8 to 9% of women
      will develop a breast cancer during their life and the incidence rate is
      regularly increasing. Despite therapeutic improvements, breast cancer mortality
      still remains important and varying according to regions (five years survival: 62
      to 80% for the last years). The risks factors analysis shows that a primary
      prevention of the major risks factors is not yet possible (genetic or endogenous
      hormonal risk). The chemoprevention is still is discussion and under
      investigation. For the moment, secondary prevention using screening is the only
      way to improve survival. The lead-time induced by the screening allows an earlier
      detection of breast cancers. The randomized trials have demonstrated a
      significant benefit on mortality and morbidity from breast cancer in women aged
      50 to 69. So many countries started regional, pilot or national breast cancer
      screening programmes using mammography with a 2-year interval and specialized
      centers.

PMID- 9781207
TI  - [Pathological anatomy of breast cancers].
AB  - Carcinomas are by far the most frequent malignant tumors of the breast. Screening
      by mammography has considerably increased the number of breast biopsies for
      mammographic abnormalities without a palpable mass. The role of the pathologist
      is to: 1. accurately diagnose specimens and ensure quality control, and 2.
      provide clinicians with all the informations required for staging and appropriate
      treatment without being led astray by the new prognostic factors based on
      biological markers in fashion.

PMID- 9781208
TI  - [Diagnostic and pretherapeutic management of breast cancer].
AB  - Breast cancer diagnostic is based on clinical examination, mammographic and
      echographic findings and the results of pathological samplings. The development
      of breast cancer screening has led to the discovery of numerous infraclinical
      lesions and in spite of this, clinical examination remains very important to
      perform, and useful for staging. Thank to the progresses of mammography and
      echography the size of discovered tumors has regularly shrunk within 15 years.
      Quality control is a necessity to obtain good and liable results. The
      ultrasonographic and stereotactic guidances are very useful to improve the
      localisation of subclinical breast cancers for sampling as well as for the
      quality and the precision of the surgery. The pretherapeutic staging needs to be
      tailored to each case and can be helped by biological markers, chest X-ray, bone
      scan and hepatic ultrasonography.

PMID- 9781209
TI  - [Prognostic factors and therapeutic strategy of breast cancer].
AB  - The survival of patients with breast cancer depends on parameters known as
      prognostic factors. The first generation of prognostic factors are simple, have
      been validated, and have proved their usefulness. We know the importance of
      examining axillary lymph nodes. However, because there has been a constant
      increase in the percentage of patients with no invaded lymph nodes, tumor size
      has become an important parameter. The 10-year survival rate of patients with
      tumors less than 1 cm in diameter exceeds 90% suggesting that there might seem to
      be no need for adjuvant therapy. According to histological grade assessed by the
      Scarff-Bloom and Richardson method, grade I tumors have a better prognosis than
      grade II or III tumors. Knowledge of the concentration of estrogen and
      progesterone receptors in tumors provides not only prognostic information but
      also indicates whether hormone therapy is justified. All these first generation
      factors are intimately linked and, taken together, they are the main factors on
      which the oncologist bases his decision whether or not to prescribe adjuvant
      therapy. There is still no consensus regarding the assay methods and normal
      levels of second generation prognostic factors. Amongst these factors, the most
      promising are those, like S-phase determination by flow cytometry, that evaluate
      cell proliferation potential and those that investigate tumor invasiveness by
      assaying urokinase plasminogen activator or its inhibitor.

PMID- 9781211
TI  - [Chemotherapy and hormonotherapy of breast cancers].
AB  - The interest of adjuvant chemotherapy and hormonotherapy is now established in
      breast cancer. Their indications are more and more precise, even though
      progresses are still warranted to better take into account the prognostic factors
      in treatment strategies. Metastatic breast cancer is essentially incurable.
      However, a standard therapy given according to the clinical and biological
      presentation is able to insure acceptable response rate, overall survival and
      quality of life. For these reasons, innovative strategies may be evaluated under
      good medical practice conditions and considered as an ethical obligation.

PMID- 9781210
TI  - [Locoregional treatment of breast cancer: surgery and radiotherapy].
AB  - Locoregional control of breast cancer can be achieved with surgery and
      radiotherapy. Surgery and irradiation is advocated for in situ carcinoma and
      invasive breast cancer. For T4 lesions, breast cancer locoregional treatment must
      be performed after neoadjuvant therapy. Locoregional recurrences without distant
      metastasis need radical surgery with or without neoadjuvant chemotherapy.
      Locoregional control of breast cancer is a part of the multidisciplinary approach
      of this disease.

PMID- 9781212
TI  - [Breast reconstruction after mastectomy for cancer].
AB  - In spite of advances in breast cancerology, partial or total mastectomy still has
      wide indications and remains a mutilative procedure. Since its introduction over
      thirty years ago, breast reconstruction has become an accepted, codified and
      efficient procedure. The techniques which can be used can be broadly divided into
      two categories: reconstructions with implants, which have been greatly improved
      by skin expansion techniques, and reconstructions using myocutaneous flaps.
      Whatever method is used, the breast is modeled during the reconstruction
      procedure and surgery is frequently necessary to obtain a symmetric opposite
      breast; a good knowledge of plastic surgery is thus a requisite.

PMID- 9781213
TI  - [Surveillance of a woman treated for breast cancer].
AB  - The intensive follow up of breast cancer patients is not safer than a minimalist
      policy for breast cancer surveillance. The survival rate is not modified by the
      use of expensive exams. The follow up program is anxiogenous, delay the
      reinsertion of the patients and useless because in 75% of cases the patient
      herself discovered the relapse. A good clinical examination, including
      gynaecological examination and a mammography are sufficient for a good follow up
      practice. The guidelines for the follow up of breast cancer patients include self
      examination of the breast monthly, clinical examination twice a year and an
      annual mammography during five years and an annual clinical examination and a
      mammography after. The radiotherapist, the surgical or medical oncologist should
      be involved with the general practitioner for this follow up.

PMID- 9781214
TI  - [Lectures].

PMID- 9781215
TI  - [Gall bladder lithiasis. Epidemiology, physiopathology, diagnosis, treatment].

PMID- 9781216
TI  - [Atropine].

PMID- 9781217
TI  - [Persistent fever (longer than 20 days)].

PMID- 9781218
TI  - [Pregnancy and diabetes (including gestational diabetes].

PMID- 9781219
TI  - [Atheroma].

PMID- 9781220
TI  - [Influenza].

PMID- 9781221
TI  - [Centenarians: exceptional elderly?].

PMID- 9781223
TI  - [The birth of hospital biochemistry].

PMID- 9781222
TI  - [Current diagnostic strategy in pulmonary embolism].

PMID- 9781224
TI  - [Mechanisms and causes of cerebral ischemic accidents].
AB  - The treatment of an ischaemic stroke requires the understanding of its mechanism
      and the diagnosis of its cause. Two main pathophysiologic mechanisms are
      implicated: thromboembolic occlusion and hemodynamic failure. The knowledge of
      the pathophysiology is crucial to the therapeutic options particularly as regards
      anti-thrombotic treatments and strict bed rest. As regards etiology, most
      ischaemic strokes are due to 3 conditions: large artery atheroma, cardiac
      diseases and small perforating arteries diseases. There are numerous other causes
      (arterial, toxic, metabolic...) which are rare but must be looked for
      particularly in young subjects devoid of cardiac diseases. The discovery of a
      cause is important for the acute treatment of an ischaemic stroke and for the
      choice of secondary prevention measures.

PMID- 9781225
TI  - [Clinical diagnosis of cerebral ischemic accidents].
AB  - The diagnosis of stroke is relatively easy in the elderly. However, this is not
      the case for transient ischemic attacks or when misleading or unusual symptoms
      are present. Clinical examination remain an essential step: being fast,
      inexpensive and always possible by the family doctor, it permits to decide
      quickly how to handle the patient and to estimate the localization and the
      mechanism of the vascular lesion, which is necessary in order to guide and
      interpret complementary examinations. Given the now available treatments, it
      seems essential to inform the public on the cerebral vascular signs and symptoms.
      Indeed, recognition of transient ischemic attacks and hospital admission delays
      for strokes have to be improved.

PMID- 9781226
TI  - [Etiological investigations in cerebral ischemic accidents].
AB  - First-line investigations for all patients include full blood count, erythrocyte
      sedimentation rate, plasma glucose, plasma cholesterol, plasma electrolytes,
      creatinine. ECG, chest X-ray and colour Doppler sonography of the neck. Carotid
      selective arteriography is performed when colour Doppler of the symptomatic
      carotid artery shows a stenosis of about 70% or more, provided the patient is fit
      for carotid endarterectomy. The search for paroxysmal atrial fibrillation is
      worthwhile in patients with palpitations. Transesophageal echocardiography is
      indicated if a cardiac source of embolism is suspected on the basis of clinical
      examination, ECG or chest X-ray and in patients without any apparent cause of
      stroke, if an embolic mechanism is likely. Finally, in the young patient
      atherosclerosis is so rare that special etiological investigations are justified.

PMID- 9781227
TI  - [Cerebral venous thrombosis].
AB  - Cerebral venous thrombosis shows remarkable clinical polymorphism: isolated
      intracranial hypertension, cerebrovascular accident or focal, subacute cerebral
      lesion. Magnetic resonance imaging permits easy identification of the thrombosis
      and its tissular consequences as well as long-term follow-up. Search for the
      cause should be meticulous, given the multiple possibilities, presently dominated
      by prothrombotic states (postpartum, haemostasis anomalies, systemic affections,
      haematologic diseases, birth control pill, etc.). The development of neuro
      imaging is changing the classic severity of cerebral venous thrombosis. Anti
      coagulant treatment is widely used, including during haemorrhagic infarction.
      This treatment probably contributes to improving the survival and functional
      prognosis.

PMID- 9781228
TI  - [Prevention of cerebral ischemic vascular accidents].
AB  - Application of all the measures for primary ischaemic stroke prevention is of
      major importance because they have a dramatic clinical effect. They are including
      the modification of lifestyle such as the level of physical activity,
      alimentation and cigarette smoking. Medications lowering blood pressure, serum
      cholesterol and glucose levels, and anticoagulants when atrial fibrillation is
      diagnosed are of proven efficacy. All these measures are also efficient in
      secondary prevention. Antiplatelets agents in case of atherothrombotic stroke and
      anticoagulants for cardioembolic stroke are of evident value. Evidence of
      efficacy of carotid surgery is clearly established for symptomatic tight
      stenosis. It could be expected that the application to a population of all these
      measures could result in a more than 50 percent decrease in incidence of
      ischaemic stroke.

PMID- 9781229
TI  - [Prognosis of cerebral ischemic accidents].
AB  - One of the roles of neurologists is to determine the prognosis in patients with
      cerebral infarction. However, it remains difficult to determine the prognosis at
      the individual level. Patients with cerebral infarction are at risk of death,
      stroke recurrence, intercurrent complications and sequelae. A clinical
      improvement may occur years after stroke onset, especially for neuropsychological
      deficits. Predictors of outcome may lead to a more appropriate management of
      stroke patients and an optimization of the reinsertion.

PMID- 9781230
TI  - [Cerebral infarction: a diagnostic and therapeutic emergency].
AB  - Emergency management of cerebral infarct aims to confirm the diagnosis, determine
      the mechanism and the cause (on which depend the prognosis and treatment),
      prevent and treat immediate, general and neurologic complications and to begin as
      early as possible the appropriate treatment. A first progressive step was made
      with the creation of hospital units devoted to management of cerebrovascular
      accidents. Various studies showed that patients hospitalised in such units have
      not only better survival and functional prognosis, but also that the length of
      hospitalisation and the number of patients requiring subsequent hospitalisation
      in rehabilitation centres are significantly reduced. More recently, clinical
      trials suggested that thrombolytic treatment, although comprising a risk of
      severe cerebral haemorrhage, can clearly improve patient prognosis if it is given
      in the first hours. Cerebral infarct should henceforth be considered as a medical
      emergency, and our health care system should be adapted to give patients the best
      chance of cure.

PMID- 9781231
TI  - [...and then comes the standardized patients (I)].

PMID- 9781232
TI  - [Third party hospitalization request and mandatory placement, guardianship,
      trusteeship, legal protection].

PMID- 9781233
TI  - [Circulatory arrest].

PMID- 9781234
TI  - [Acute nasal-sinus infections in the adult].

PMID- 9781235
TI  - [Fracture of the lower humerus in children].

PMID- 9781236
TI  - [Small cell bronchial cancers].

PMID- 9781237
TI  - [Epilepsy in children].

PMID- 9781238
TI  - [Monofactorial heredity].

PMID- 9781239
TI  - The Annual meeting of the European Academy of Allergology and Clinical
      Immunology. EAACI '98. Birmingham, United Kingdom, June 21-26, 1998. Abstracts.

PMID- 9781241
TI  - [Proceedings of the Endocrine Society 79th annual congress. Minneapolis,
      Minnesota, USA. 11-14 June 1997].

PMID- 9781240
TI  - Cumulative indexes--volumes 26-50.

PMID- 9781242
TI  - [Dermatology meeting, Paris, France, 3-6 December 1997. Abstracts].

PMID- 9781243
TI  - 8th International Congress of Pediatric Dermatology, Paris, 17-20 May 1998.
      Abstracts.

PMID- 9781244
TI  - 10th NCI-EORTC symposium on new drugs in cancer therapy. Amsterdam, June 16-19,
      1998. Abstracts.

PMID- 9781246
TI  - 69th Meeting of the European Atherosclerosis Society. Hanasaari, Finland, 24-26
      May 1998. Abstracts.

PMID- 9781245
TI  - Cardiostim 98. 11th International Congress of the French Society of Cardiology.
      Nice Acropolis, 17-20 June 1998. Abstracts.

PMID- 9781247
TI  - Psychiatry at the Interface. 33rd Congress of the Royal Australian and New
      Zealand College of Psychiatrists. Melbourne, Victoria, 24-28 May 1998. Abstract.

PMID- 9781248
TI  - Society for the Study of Reproduction 31st annual meeting. College Station,
      Texas, USA. August 8-11, 1998. Abstracts.

PMID- 9781249
TI  - British Society of Audiology Short Papers Meeting on Experimental Studies of
      Hearing and Deafness. Nottingham, 22-23 September 1997. Abstracts.

PMID- 9781250
TI  - 5th Congress of the European Society of Contraception. Prague, 17-20 June, 1998.
      Abstracts.

PMID- 9781251
TI  - 33rd Congress of the European Society for Surgical Research (ESSR). Padua, Italy,
      April 22-25, 1998. Abstracts.

PMID- 9781253
TI  - XIV International Congress "The Fetus as a Patient" and XII International
      Congress "Fetal Cardiology". Amsterdam, The Netherlands, May 12-15, 1998.
      Abstracts.

PMID- 9781252
TI  - 16th European Workshop on Drug Metabolism. Copenhagen, Denmark, June 21-26, 1998.
      Abstracts.

PMID- 9781254
TI  - Cumulative author, subject, compound and special issue indexes. Volumes 752-800
      (1996-1998).

PMID- 9781256
TI  - Rehabilitation research and development progress reports 1997.

PMID- 9781255
TI  - Proceedings of the Physiological Society, University of Liverpool meeting. 27-29
      April 1998. Abstracts.

PMID- 9781257
TI  - History of the American Association of Physicists in Medicine, 1958-1998.

PMID- 9781258
TI  - [German Society for Psychiatry, Psychotherapy and Neurology. 1998 Congress.
      Essen, 17-20 June. Abstracts].

PMID- 9781259
TI  - Advances in Gene Technology: Molecular Biology in the Conquest of Disease. Miami
      Nature Biotechnology winter symposium. Miami, Florida, USA. February 7-11, 1998.

PMID- 9781260
TI  - VIIIth Congress of the International Society for Peritoneal Dialysis. ISPD 98.
      Seoul, Korea, August 23-26, 1998. Abstracts.

PMID- 9781262
TI  - Annual Brachytherapy Meeting. GEC-ESTRO. Naples, Italy, 11-13 May 1998.
      Abstracts.

PMID- 9781261
TI  - 9th International Symposium on Vascular Neuroeffector Mechanisms. Porto,
      Portugal, 2-5 August 1998. Abstracts.

PMID- 9781263
TI  - New therapeutic approaches for allergic diseases of the respiratory tract.
      Euroconference, Paris, France, April 1-4, 1998, Abstracts.

PMID- 9781265
TI  - Laboratory Medicine 98. XXVI Nordic congress of Clinical Chemistry. Turku,
      Finland, June 6-10, 1998. Abstracts.

PMID- 9781264
TI  - [Pneumology Society of the French Langue membership list 1998].

PMID- 9781266
TI  - Swedish Association of Urology spring meeting. Uppsala, June 10-12, 1998.
      Abstracts.

PMID- 9781267
TI  - Haptoglobin genotyping by allele-specific polymerase chain reaction
      amplification.
AB  - We performed haptoglobin (Hp) genotyping by polymerase chain reaction using
      allele-specific primer-pairs. The major six genotypes of Hp were identified using
      this method. Among Japanese individuals living in Ehime and Okayama Prefectures,
      the allele frequencies were estimated to be Hp2 = 0.723 and Hp1s = 0.277.
      Genotyping of Hp was possible with 0.3 ng of DNA and with 0.125 microliter of
      blood. It was also possible with whole blood left at room temperature for a month
      and also with the bloodstains left at room temperature for three years. In the
      heated blood samples, both alleles, Hp2 and Hp1s, were detected in those heated
      at 100 degrees C for 2 h. In bloodstains, Hp2 and Hp1s were detected in samples
      heated at 100 degrees C for 2 h and 120 degrees C for 30 min. In addition, the
      genotype could be detected in samples other than blood such as saliva, hair
      roots, tissue sections and dental pulps. The present method for Hp genotyping is
      expected to become a useful method in forensic analysis.

PMID- 9781268
TI  - The effect of L-carnitine on platelet activating factor concentration in the
      immature rat model of hypoxic-ischemic brain injury.
AB  - Recent data suggested that platelet-activating factor (PAF) could play a
      pathophysiologically important role in the progression of hypoxic-ischemic brain
      injury. We investigated brain tissue PAF concentration in the hypoxic-ischemic
      brain of immature rats. Endogenous PAF concentration in brain tissue showed a
      marked increase in hypoxic-ischemic pups (Group 1, 85.6 +/- 15.5 pg/mg protein)
      when compared to that of the control (9.1 +/- 3.1 pg/mg protein). In addition, we
      studied the effects of pretreatment with L-carnitine (5 days and 2 h before the
      hypoxia) on endogenous PAF concentration in the hypoxic-ischemic brain.
      Endogenous PAF concentration in the short-term pretreatment group (Group 2, 81.6
      +/- 9.7 pg/mg protein) was not different than in Group 1 rat pups. However, a
      significantly decreased PAF concentration was found in the group of pups that
      received carnitine pretreatment for 5 days (Group 3, 30.5 +/- 11.0 pg/mg
      protein). These results indicate that PAF is an important mediator in the
      immature rat model of cerebral hypoxic-ischemic injury. The suppressor effect of
      L-carnitine on PAF production may give new insight into the treatment of hypoxic
      ischemic brain injury.

PMID- 9781269
TI  - Typology of abdominal arteries, with special reference to inferior phrenic
      arteries and their esophageal branches.
AB  - Origins and distribution of the human inferior phrenic arteries were studied by
      dissecting 68 Japanese adult cadavers. The inferior phrenic arteries were usually
      observed as paired (left and right) vessels. Their origins were summarized as
      follows: a) the aorta itself (85/138 cases, 61.6%), b) the ventro-visceral
      arteries (celiaco-mesenteric system of the aorta) including the celiac trunk
      (39/138 cases, 28.2%) and the left gastric artery (4/138 cases, 2.9%), and c) the
      latero-visceral arteries (adreno-renal system of the aorta) including the middle
      adrenal artery (4/138 cases, 2.9%) and the renal artery (6/138 cases, 4.3%). The
      left and right arteries occasionally originated in common trunk from the aorta,
      celiaco-mesenteric system or adreno-renal system (22/138 cases, 15.9%). A
      typological diagram explaining these variations is given. The inferior phrenic
      arteries, especially the left ones, sometimes issued visceral or esophageal
      branches. This fact indicates that the inferior phrenic arteries are homologous
      with the celiac trunk and mesenteric arteries. It is further discussed that the
      celiac trunk and mesenteric arteries are originally paired vessels, through
      introduction of our previous typological diagram of the abdominal arteries.

PMID- 9781270
TI  - Different expression of Tn and sialyl-Tn antigens between normal and diseased
      human gastric epithelial cells.
AB  - Thomsen-Friedenreich antigen (T antigen) has been supposed to be a cancer
      specific carbohydrate antigen. We have previously shown that one third of the
      Japanese population normally expressed T antigen in gastric surface epithelia and
      the other two thirds expressed fucosyl-T antigen. Their sialylation and blocked
      synthesis were associated with diseased conditions. In the present study, we
      studied gastric surface epithelial expression of monosaccharide antigen Tn, i.e.,
      a precursor of T antigen, and sialyl-Tn. Normal fundic and pyloric epithelia,
      respectively, expressed Tn supranucleally and cytoplasmically, but did not
      express sialyl-Tn. In the intestinal metaplasias and intestinal-type adenomas,
      goblet cells expressed sialyl-Tn in their vacuoles, and absorptive cells
      expressed Tn apically. In gastric-type adenomas, Tn, but not sialyl-Tn, was
      detected. Intestinal-type cancers expressed Tn and sialyl-Tn more often than the
      diffuse-type cancers. Five cancers did not express Tn, sialyl-Tn, or the T
      related antigens. In these, four were diffuse-type cancers. We concluded that: a)
      normal gastric epithelial cells express Tn; b) metaplastic differentiation is
      associated with sialylation of Tn and c) expression of Tn and sialyl-Tn is
      depressed in the gastric cancers.

PMID- 9781271
TI  - Ultrastructural and biochemical changes of the brain after peripheral
      administration of phorbol myristate acetate.
AB  - The ultrastructural and biochemical changes in the brain tissue of 20 mice were
      studied. The mice, separated into acute and chronic groups, were injected with
      phorbol myristate acetate (PMA) to trigger the release of free radicals.
      Malondialdehyde measurement and electron microscopic examination were applied for
      the evaluation of the effects of the free radicals. The level of lipid peroxide
      in the chronic PMA group was found to be significantly higher than it was in the
      acute PMA group (P < 0.005). An electron microscopic examination of the acute
      group revealed disruption of the mitochondrial cristae and dilatation of the
      endoplasmic reticulum in the neurons. Myelin sheaths of the nerve fibers
      exhibited focal structural changes. Neurons and neuroglial cells in the chronic
      group, however, exhibited distinct ultrastructural alterations. The
      ultrastructural and biochemical findings showed that free radicals lead to brain
      damage.

PMID- 9781272
TI  - Evaluation of rheumatoid arthritis using a scoring system devised from magnetic
      resonance imaging of rheumatoid knees.
AB  - We studied the magnetic resonance imaging (MRI) of 120 knees in 86 rheumatoid
      arthritis (RA) patients and of 14 unaffected knees in 12 control cases. We also
      developed a scoring system as a quantitative analysis method. We divided the MRI
      into 10 items, and classified the severity of the symptoms into 4 grades (score 0
      to 3). The average total score increased according to the radiographic grade.
      Soft tissue lesions were clearly detected, even in the early stages of RA. Items
      such as synovial proliferation showed a high score even in the early stages,
      suggesting that it was the initial symptom of RA. The score also showed a
      correlation with the inflammatory signs. These results suggest that this scoring
      system is very sensitive and yields a good reflection of RA activity. We
      demonstrated that this system is simple and convenient for routine diagnostic
      use. We further demonstrated that it is useful for following the advancement of
      RA and for evaluating the response to treatment.

PMID- 9781274
TI  - Surgical treatment of lumbar spinal stenosis in the elderly.
AB  - 148 elderly patients, aged 70 years or more, diagnosed as having lumbar spinal
      stenosis, were operated upon at our institution during 1983 to 1995. Totally 161
      operative procedures were performed. We analysed retrospectively the results of
      the surgical treatment. The most frequently performed procedure was
      multisegmental laminectomy, in 32% interlaminar fenestration and laminotomy were
      done. In 9 cases fusion was indicated, two of them being secondary operations.
      The mean hospital stay was 11 days. The morbidity was 6%, and there was one
      fatality (0.6%). The outcome was determined according to the six-grade
      classification proposed by Pappas and Sonntag [25]. Overall, in 91% of cases
      satisfactory-to-excellent results could be achieved. We conclude, that in elderly
      patients with symptomatic lumbar spinal stenosis, with no evidence of
      instability, decompressive surgery without stabilisation can be done in the
      majority of patients with low morbidity and high expectation of clinical
      improvement.

PMID- 9781273
TI  - Association of fatty liver with increased ratio of visceral to subcutaneous
      adipose tissue in obese men.
AB  - We studied the association of fatty liver with subcutaneous and visceral obesity
      in 46 male and 36 female patients with body mass index (BMI) over 22 kg/m2. The
      correlation coefficient between the ratio of the visceral adipose tissue to the
      subcutaneous adipose tissue (V/S) and the computed tomography (CT) number of the
      liver was -0.299 (P < 0.05) and that between the V/S ratio and the ratio of the
      CT number of the liver to that of the spleen (CT-L/CT-S) was -0.335 (P < 0.05) in
      the males. Partial correlation analysis after making correction for BMI showed an
      increased correlation coefficient of -0.485 (P < 0.05) between the V/S ratio and
      the CT-L/CT-S ratio in the males. The odds ratio in the males for CT-L/CT-S below
      1.0 and V/S above 1.0 was 3.25 with a 95% confidence interval of 1.02 to 9.39. No
      such association between the V/S ratio and the CT-L/CT-S ratio was present in the
      female patients. Multiple regression analysis with serum level of alanine
      aminotransferase, a marker of fatty liver, as an independent variable revealed a
      partial regression coefficient of -17.7 for CT-L/CT-S (P < 0.05) in the males and
      -21.7 (P < 0.05) in the females, validating the CT-L/CT-S ratio as an index of
      fatty liver. The results indicate the association of fatty liver as determined by
      the CT-L/CT-S ratio with visceral obesity in males.

PMID- 9781275
TI  - Herniated thoracic discs mimic cardiac disease: three case reports.
AB  - The authors report three patients (two males and one female) with herniated
      thoracic discs whose symptoms mimicked cardiac disease (severe intense stabbing
      pain beginning in the back and radiating to the lateral wall of the chest). They
      were evaluated for cardiac disease and angina, but the workup of the heart was
      negative. Magnetic resonance imaging and computed tomography myelography revealed
      the herniated thoracic discs. All patients underwent video-assisted endoscopic
      thoracic discectomy and recovered completely.

PMID- 9781276
TI  - The cluster of arachnoid diverticula in the occipital bone: report of two cases
      with literature review.
AB  - The authors report two cases of multicentric osteolytic lesions in the occipital
      bone without any history of head trauma. The excisional biopsy of the first case
      revealed that the lesion was multicentric but a continuous cavity with the
      subarachnoid space through various sizes of dural defect, and the cavities were
      covered by arachnoid lining. Together with the previously reported similar 5
      cases, the characteristic common feature is multicentric osteolytic lesions in
      the occipital bone at advanced age without marginal sclerosis. "The cluster of
      arachnoid diverticula in the occipital bone (CADOB)" is probably the most
      appropriate term for these non-traumatic lesions with the following
      characteristics: elderly patients, occipital bone, midline, multiple, intact
      outer table, nonsclerotic margin and without history of trauma. Operation may not
      be indicated because of its non-progressive and benign nature.

PMID- 9781277
TI  - The natural history of late diagnosed or untreated growing skull fractures:
      report on two cases.
AB  - Growing skull fractures (GSF) are rare complications of head trauma. Cases after
      childhood are extremely rare and demonstrate complicated pathological conditions
      which necessitate extensive treatment. We report on two rare cases of
      intracranial cysts related to growing skull fractures which are secondary to
      trauma sustained during childhood, and have been discovered in adolescence.

PMID- 9781278
TI  - Traumatic subdural pneumocephalus causing rise in intracranial pressure in the
      early phase of head trauma: report of two cases.
AB  - This paper presents two unique cases of subdural tension pneumocephalus which has
      deteriorated in the early phase of head trauma. Subdural pneumocephalus accounts
      for about 25% of all intracranial pneumocephalus cases. In the literature
      subdural pneumocephalus is describes as a benign and spontaneously resolving
      condition. Contrary to the available literature and our experience in 1341 trauma
      cases in the past ten years of whom 76 had subdural pneumocephalus, both cases
      deteriorated in the early hours following head trauma due to an increase in
      subdural air volume which was evacuated by craniotomy.

PMID- 9781279
TI  - Potential pitfalls in apnea testing.
AB  - To determine the influence of baseline paCO2 on the results of apnea testing in
      the diagnosis of brain death, we performed an open prospective study on 36
      patients fulfilling all other criteria for the diagnosis of brain death according
      to the criteria proposed by the Advisory Board of the German Federal Chamber of
      Physicians. For testing of apnea, patients underwent hypoventilation with 100%
      oxygen supply until a baseline paCO2 of 40 torr (5.3 kPa, n = 24, group 1) or 60
      torr (8.0 kPa, n = 12, group 2) was reached. Then, patients were disconnected
      from the ventilator and apneic oxygenation with insufflation of 61 O2/min into
      the tracheal cannula was performed for five minutes. Arterial blood gas samples
      were obtained every minute during the testing period. In parallel, patients were
      observed for signs of spontaneous breathing. All patients remained apneic during
      the five minute test period. No relevant hypoxia (paO2 < 80 torr [10.6 kPa]) was
      observed in either group. In group 1, a mean baseline paCO2 of 45 torr (6.0 kPa)
      was registered, mean end-paCO2 was 75 torr (10.0 kPa). In group 2, paCO2 values
      were 66 torr (8.8 kPa) and 90 torr (12 kPa), respectively. Baseline pH in group 1
      (7.32) decreased to 7.18 at the end of testing and from 7.23 to 7.13 in group 2.
      Patients in group 2 were in possible danger of developing a CO2-induced narcosis
      mimicking apnea. Secondary organ damage due to severe respiratory acidosis could
      not be excluded in the patients of group 2. As no complications were observed in
      group 1 and apnea was evident in all these patients, we consider a baseline paCO2
      of 40 torr (5.3 kPa) sufficient to establish apnea after five minutes of apneic
      oxygenation if an increase of baseline paCO2 of at least 20 mmHg is documented by
      arterial blood gas sampling. A higher baseline paCO2 may endanger patients
      without yielding more specific testing results.

PMID- 9781280
TI  - Whole-body [18F]FDG PET in the management of metastatic brain tumours.
AB  - BACKGROUND: To determine its roles in the diagnosis and the systemic evaluation
      of metastatic brain tumours, whole-body positron emission tomography (PET) using
      [18F]FDG was performed in 20 consecutive patients. METHODS: All patients were
      thought to be suffering or needing to be differentiated from metastatic brain
      tumours. Nine patients had multiple brain lesions; six were older and showed a
      rim-enhancing lesion with surrounding oedema; seven had homogeneously enhancing
      periventricular lesion(s) on computed tomography (CT) and/or magnetic resonance
      (MR) imaging, thought to be central nervous system lymphomas. Two patients had
      skull mass(es) and two patients had a solid mass suspected to be, respectively, a
      haemorrhagic metastasis and a metastatic malignant melanoma. All of them received
      whole-body [18F]FDG PET and conventional systemic work-up for metastasis in order
      to compare the results of the two methods. RESULTS: Metastatic brain tumours were
      diagnosed on whole-body [18F]FDG PET in eleven patients who had extracranial and
      intracranial hypermetabolic lesions. In nine of these, a conventional work-up
      also detected primary lesions which on whole-body [18F]FDG PET were seen to be
      hypermetabolic foci. Systemic lymph node metastases were detected by whole-body
      [18F]FDG PET only in two patients and histological diagnosis was possible by
      biopsy of lymph nodes rather than of brain lesions. In the remaining nine
      patients who had only intracranial hypermetabolic foci, histological diagnosis
      was made by craniotomy or stereotactic biopsy. It was confirmed that seven of
      nine patients were suffering from a primary brain tumour and two from metastatic
      carcinoma. None of the nine showed evidence of systemic cancer on conventional
      work-up. Histological diagnoses of the primary brain tumours were four cases of
      primary central nervous system lymphoma and one each of multifocal glioblastoma,
      Ewing's sarcoma, and cavernous angioma. Patients felt no discomfort during the
      whole-body [18F]FDG PET procedure and there were no complications. The false
      negative rate in [18F]FDG PET and in conventional work-up was 15.4% and 30.7%
      respectively. There were no false positives on either [18F]FDG PET or
      conventional work-up. CONCLUSION: It is suggested that whole-body [18F]FDG PET is
      a safe, reliable, and convenient method for the diagnosis and systemic evaluation
      of patients thought to be suffering or needing to be differentiated from a
      metastatic brain tumour.

PMID- 9781281
TI  - Intrameatal tumours presenting as a hearing disturbance: case reports of
      meningioma and lymphoma.
AB  - This paper presents two patients with chronic progressive hearing disturbance.
      Each patients had an intrameatal tumour, part of which extended to the
      cerebellopontine (CP) angle. In both cases, the patients were initially diagnosed
      with an acoustic neurinoma. A 63-year-old male experienced a hearing disturbance
      in the left ear for 1.5 years prior to visiting our hospital. Magnetic resonance
      (MR) imaging revealed a mass which was surgically resected. The tumour originated
      from the intrameatal dura mater. Histologically, the tumour was a meningioma.
      Similarly, a 53-year-old male presented with systemic lymphoma diagnosed 10
      months earlier, and a hearing disturbance in the right ear that began 3 months
      prior to visiting our hospital. MR imaging prior to chemotherapy revealed a mass
      which extended to the CP angle. Part of the tumour in the CP angle disappeared
      after chemotherapy, suggesting a secondary lymphoma. Another tumour appeared
      later in Meckel's cave on the left side; however, it decreased in size following
      repeated chemotherapy. The present results indicate that differential diagnosis
      of intrameatal tumours and acoustic neurinomas may be difficult due to the small
      tumour size. Recent progress in neuroradiology may allow distinction of
      intrameatal tumours as a separate tumour classification. Our second patient is
      the sixth reported case of a CP angle lymphoma in the literature.

PMID- 9781282
TI  - Correlation between latency and amplitude of peak V in the brainstem auditory
      evoked potentials: intraoperative recordings in microvascular decompression
      operations.
AB  - Intraoperative prolongation of the latency and decrement of the amplitude of peak
      V of brainstem auditory evoked potentials (BAEP) were studied in 38 microvascular
      decompression operations in which prolongation of the latency of peak V exceeded
      1.0 msec. Postoperative hearing tests of all patients were compared with their
      preoperative hearing tests. Postoperative hearing loss was unrelated to the
      maximum prolongation of latency, but the amplitude decreased to lower values in
      patients with postoperative hearing loss compared to patients whose postoperative
      hearing was unchanged (P < 0.05). Twelve (32%) of 38 patients whose latency of
      peak V was prolonged more than 1.0 msec and 11 (61%) of 18 patients whose
      amplitude of peak V decreased more than 40% during the operations had decreased
      hearing postoperatively. In all patients, a prolongation of the latency of peak V
      was always accompanied by a decrease in the amplitude of peak V. The decrement of
      the amplitude was greater in the patients with decreased postoperative hearing
      thresholds than in the patients with unchanged postoperative hearing thresholds.
      The results of this study indicate that it would be valuable to monitor changes
      in the amplitude of peak V of BAEP in addition to monitoring the latency of peak
      V during operations where the VIIIth cranial nerve is manipulated.

PMID- 9781283
TI  - Intra-operative colour-duplex-sonography in the surgical management of cerebral
      AV-malformations.
AB  - In this prospective study the role of intra-operative Colour-Duplex-Sonography (=
      CDS) during surgery of arteriovenous malformations (= AVM) is evaluated. During
      the last three years 20 consecutive patients with supratentorial AVMs were
      examined by intra-operative CDS in order to evaluate the potential of CDS to 1)
      localize the AVM, 2) differentiate between embolized and perfused parts, 3)
      identify feeding and draining vessels and 4) control the complete excision of the
      AVM. All AVMs were localized supratentorially, 9 were grade I and II (according
      to Spetzler and Martin [31]), 8 grade III and 3 grade IV. 11 were partly
      embolized and 8 associated with an intracerebral bleeding. In all cases the nidus
      was correctly localized sonographically by its typical bidirectional flow pattern
      in Colour-mode. CDS guided the surgeon directly to all (11 cases) deep-seated
      AVMs (2 to 4 cm subcortically). The smallest nidus measured 10 mm. 28 of 34
      angiographically defined main feeding and 18 of 23 draining vessels were
      identified. 14 patients were controlled sonographically at the end of the
      resection regarding the completeness of excision. In 11 patients CDS was negative
      and was confirmed by either postoperative angiography or MRI in 10 patients. In
      one case residual AVM tissue was missed by CDS. Positive CDS findings in 3 cases
      were all confirmed by microscopic re-inspection, angiography and CCT. Our results
      suggest that CDS is able to localize AVMs intra-operatively with minimal
      instrumentation. It allows safe navigation to deep-seated malformations with high
      accuracy. Feeding and draining vessels can be identified and completeness of
      resection can be controlled.

PMID- 9781284
TI  - Effect of cerebral ischaemia on the cerebrovascular and cardiovascular response
      to haemorrhage.
AB  - Reports studying the combination of low blood pressure and cerebral ischaemia are
      few, and it remains to be determined how cerebral circulatory insufficiency
      modifies the cerebral perfusion and the central haemodynamic response to blood
      loss. We hypothesised that occlusion of arteries to the brain modifies the
      cerebrovascular and cardiovascular responses to blood loss. Continuous
      measurements of the cerebral microcirculation with laser Doppler microprobes in
      the cerebral cortex were performed in anaesthetised pigs during cerebral
      ischaemia and haemorrhagic hypotension. The response to rapid bleeding (25% of
      the blood volume) was recorded during normal conditions and during cerebral
      ischaemia induced by bilateral occlusion of the common carotid arteries. During
      normal conditions haemorrhage caused insignificant decreases in cerebral
      microcirculation. Haemorrhage during bilateral carotid artery occlusion, however,
      caused significantly greater changes in cerebral microcirculation and a greater
      posthaemorrhagic increase in cerebrovascular resistance shortly after the blood
      loss. Haemorrhage during bilateral carotid artery occlusion also caused greater
      reductions in cardiac output and arterial pressure than similar blood loss caused
      during normal conditions. This study showed a disproportionate decrease in
      cerebral blood flow with haemorrhage during bilateral carotid occlusion, caused
      by an immediate increase in cerebrovascular resistance. The results suggest that
      even a moderate blood loss in patients with impaired cerebral circulation could
      be dangerous, because normal compensatory mechanisms to haemorrhage are impaired.

PMID- 9781285
TI  - Vitamin D metabolites activate the sphingomyelin pathway and induce death of
      glioblastoma cells.
AB  - 1 alpha, 25-dihydroxyvitamin D3 was previously shown to induce cell death in
      brain tumour cell lines when added to the medium at micromolar concentration. In
      this paper we show that Cholecalciferol, a poor ligand of the vitamin D receptor,
      also induces cell death of HU197 human glioblastoma cell line and early passages
      cultures derived from a recurrent human glioblastoma. This finding suggests that
      the effects of vitamin D metabolites on brain tumour cells are at least partially
      independent from the activation of the classic nuclear receptor pathway. Vitamin
      D metabolites have been shown to activate the sphingomyelin pathway inducing an
      increase in cellular ceramide concentration. We determined the levels of
      sphingomyelin ceramide and ganglioside GD3 in Hu197 cells after treatment with
      cholecalciferol. A significant increase in ceramide concentration and a
      proportional decrease in sphingomyelin was already present after 6 hours of
      cholecalciferol treatment when no morphological changes were visible in the
      cultures. Treatment with ceramides (N-acetylsphingosine or natural ceramide from
      bovine brain) of the same cells also induces cell death. Similarly, treatment of
      the same cells with bacterial Sphingomyelinase also results in cell death. The
      demonstration of an increase in intracellular ceramide after cholecalciferol
      treatment and the ability of ceramide to induce cell death suggest that the
      sphingomyelin pathway may be implicated in the effect of vitamin D metabolites on
      human glioblastoma cells. Inhibition of ceramide biosynthesis by fumonisin B1
      treatment did not alter the dose response curve of HU197 cells to
      cholecalciferol. Insensitivity to fumonisin B1 together with a decrease in
      sphingomyelin content after cholecalciferol treatment indicate that activation of
      sphingomyelinase should be responsible for the increase in intracellular ceramide
      concentration.

PMID- 9781286
TI  - Transsphenoidal-transtuberculum sellae approach for supradiaphragmatic tumours:
      technical note.
AB  - The Classic transsphenoidal approach may not afford sufficient exposure for a
      supradiaphragmatic tumour adjacent to the pituitary stalk. Various transcranial
      approaches have been utilized to access such a lesion with adequate results. This
      report describes a less invasive technique, termed "transsphenoidal
      transtuberculum sellae approach". This modified transsphenoidal approach requires
      a bone ablation of the tuberculum sellae, the limbus sphenoidalis, and a portion
      of the planum sphenoidale, in addition to an opening of the anterior floor of the
      sella turcica. The dura mater on the tuberculum sellae and the pituitary fossa is
      sectioned with a bilateral obliteration of the anterior intercavernous sinus. The
      anterior pituitary gland is not necessarily resected. The optic chiasm, optic
      nerves, pituitary stalk, and tuber cinereum can be directly observed, making it
      possible to safely dissect a lesion from these structures. Utilizing this
      approach, we have removed 14 supradiaphragmatic tumours without complications and
      dealt with other lesions such as optic nerve injuries or cerebrospinal fluid
      rhinorrhea, leaving pituitary function intact. The transsphenoidal
      transtuberculum sellae approach for accessing small supradiaphragmatic tumours is
      a useful procedure requiring only a minor modification of the classic
      transsphenoidal technique.

PMID- 9781287
TI  - A new forceps for the safe and easier insertion of subdural catheter: technical
      note.
AB  - A new forceps suitable for the safe and easier insertion of a silicon catheter
      into the subdural space is described. The use of this new tool has two
      advantages: Firstly, the insertion of the silicon subdural catheter is parallel
      to the brain surface and secondly, the movement of the catheter's end in the
      subdural space is controlled with greater accuracy. Thus, the surgeon has the
      opportunity to direct the catheter to the right position avoiding penetration or
      injury of the brain.

PMID- 9781288
TI  - A multifocal cerebellar and supratentorial medulloblastoma in an adult.

PMID- 9781289
TI  - Intracranial foreign-body granuloma treated with anti-cytokine agents.

PMID- 9781290
TI  - Subdural osteoma.

PMID- 9781291
TI  - Benign osteoblastoma of the orbital part of the frontal bone: case report.

PMID- 9781293
TI  - The role of glycosylation in flavonol-induced pollen germination.
AB  - Flavonols are small (C15) plant-specific molecules that are required for petunia
      and maize pollen to germinate. They exist in two chemical forms: the aglycone or
      glycosyl conjugates. Flavonol-deficient pollen is biochemically complemented by
      flavonol aglycones but not by the glycosylated forms that accumulate in wild type
      (WT) pollen. Coincident with the biochemical induction of germination, the added
      flavonol aglycone is rapidly converted to a galactoside and then to a glucosyl
      galactoside (diglycoside) that is identical to the compound present in WT pollen.
      A flavonol 3-O-galactosyltransferase (F3GalTase) activity has been identified
      that controls the formation of glycosylated flavonols in pollen. Importantly,
      this enzyme also catalyzes the reverse reaction, i.e. the production of the
      flavonol aglycone from the galactoside and UDP (Fig. 1). F3GalTase/RevGalTase
      therefore has the potential to control the level of the bioactive flavonol
      species and as a result, pollen germination.

PMID- 9781294
TI  - Expression of genes for enzymes of the flavonoid biosynthetic pathway in the
      early stages of the Rhizobium-legume symbiosis.

PMID- 9781292
TI  - Flavonoids and arbuscular-mycorrhizal fungi.
AB  - Arbuscular mycorrhizal fungi (AMF) are ancient Zygomycetes forming the most
      widespread plant-fungus symbiosis. The regulation of this association is still
      poorly understood in terms of the communication between the two partners.
      Compounds inside the root and released by the root, such as flavonoids, are
      hypothesized to play a role in this plant-fungus communication, as already
      demonstrated in other symbiotic associations (e.g. Rhizobium-leguminoseae). Here
      we give a general overview of the research concerning this question.

PMID- 9781296
TI  - Flavonoid accumulation in tissue and cell culture. Studies in Citrus and other
      plant species.

PMID- 9781295
TI  - Prospects for the metabolic engineering of bioactive flavonoids and related
      phenylpropanoid compounds.
AB  - The successful engineering of complex metabolic pathways will require, in
      addition to availability of cloned genes and promoters, knowledge of the
      regulatory mechanisms that control metabolic flux into the pathway including post
      translational phenomena such as metabolite channeling. We are interested in
      modifying pathways for the synthesis of isoflavonoids and other bioactive
      phenylpropanoid compounds in transgenic plants. We describe studies on flux
      control utilizing transgenic tobacco plants that under- and over-express key
      biosynthetic enzymes, and outline experimental approaches for the molecular
      dissection of potential metabolic channels in the synthesis of antimicrobial
      flavonoid derivatives in alfalfa and other species.

PMID- 9781297
TI  - Flavonoids of the orange subfamily Aurantioideae.

PMID- 9781298
TI  - Citrus flavonoids: a review of past biological activity against disease.
      Discovery of new flavonoids from Dancy tangerine cold pressed peel oil solids and
      leaves.

PMID- 9781299
TI  - Differentiation of soy sauce types by HPLC profile pattern recognition. Isolation
      of novel isoflavones.
AB  - Nonvolatile minor components in various brands of Japanese fermented soy sauce
      were analyzed by gradient RP-HPLC and monitored at 280 nm. Chemometric pattern
      recognition techniques, such as cluster analysis, linear discriminant analysis
      (LDA), LDA using genetic algorithm (GA-LDA) and soft independent modelling of
      class analogy (SIMCA), succeeded in differentiating the resulting HPLC profiles
      according to soy sauce brands. Three components playing key roles in the
      differentiation were isolated by preparative HPLC and purified by gel-filtration
      chromatography, or simply repeated preparative HPLC. FAB-MS, 1H-, 13C-NMR and IR
      spectra suggested that these three components having molecular weights of 386,
      402 and 418 were isoflavone derivatives. By applying HMBC spectral analysis,
      these isoflavones were identified as conjugated ethers of tartaric acid with
      daidzein, genistein and 8-hydroxygenistein. These new isoflavone derivatives are
      produced by some strains of Aspergillus fungi.

PMID- 9781300
TI  - Induction of oxidative stress by redox active flavonoids.

PMID- 9781301
TI  - Flavonoids in foods as in vitro and in vivo antioxidants.
AB  - The polyphenol antioxidants in foods and beverages are shown to be powerful in
      vitro antioxidants. The polyphenols in foods and beverages enrich low density
      lipoproteins and decrease their oxidizability ex vivo after spiking and in vivo
      after absorption of the polyphenols following ingestion of beverages. These
      studies provide mechanisms to explain the epidemiological study which shows that
      consumption of fruits, vegetables and beverages reduce the risk of cardiovascular
      and cerebrovascular disease.

PMID- 9781302
TI  - Antithrombogenic and antiatherogenic effects of citrus flavonoids. Contributions
      of Ralph C. Robbins.

PMID- 9781303
TI  - Effect of plant flavonoids on immune and inflammatory cell function.
AB  - The flavonoids are a large group of naturally occurring phenylchromones found in
      fruits, vegetables, grains, bark, roots, stems, flowers, tea, and wine. Up to
      several hundred milligrams are consumed daily in the average Western diet. Only
      limited information is available on the absorption, distribution, metabolism, and
      excretion of these compounds in man. Some compounds are absorbed, however, and
      measurable plasma concentrations are achieved which could have pharmacological
      relevance. A variety of in vitro and in vivo experiments have shown that selected
      flavonoids possess antiallergic, antiinflammatory, antiviral and antioxidant
      activities. Moreover, acting by several different mechanisms, particular
      flavonoids can exert significant anticancer activity including anticarcinogenic
      properties and even a prodifferentiative activity, amongst other modes of action.
      Certain flavonoids possess potent inhibitory activity against a wide array of
      enzymes, but of particular note is their inhibitory effects on several enzyme
      systems intimately connected to cell activation processes such as protein kinase
      C, protein tyrosine kinases, phospholipase A2, and others. Evidence suggests that
      only activated cells are susceptible to the modulating effects of flavonoids,
      i.e. cells which are responding to a stimulus. The stimulated activities of
      numerous cell types, including mast cells, basophils, neutrophils, eosinophils, T
      & B lymphocytes, macrophages, platelets, smooth muscle, hepatocytes, and others,
      can be influenced by particular flavonoids. On balance, a considerable body of
      evidence suggests that plant flavonoids may be health-promoting, disease
      preventing dietary compounds.

PMID- 9781304
TI  - Flavonoids: inhibitors of cytokine induced gene expression.

PMID- 9781305
TI  - Recent advances in the discovery and development of flavonoids and their
      analogues as antitumor and anti-HIV agents.
AB  - Antitumor and anti-HIV flavonoids and their analogues will be reviewed with
      emphasis on those discovered in our laboratory. The active antitumor compounds
      include the antileukemic tricin (1) and kaempferol-3-O-beta-D-glucopyranoside (2)
      from Wikstroemia indica, the cytotoxic hinokiflavone (3) from Rhus succedanea,
      the cytotoxic isoflavone (8) from Amorpha fruticosa, two
      dihydroxypentamethoxyflavones (9, 10) from Polanisia dodencandra. The development
      of synthetic 2-phenyl-4-quinolones as potent cytotoxic antimitotic flavonoid
      analogues and 2-phenylthiochromen-4-ones as potent antitumor flavonoid analogues
      will be presented. Selected results from other laboratories and antitumor-related
      biological studies also will be discussed. Flavonoids have also been investigated
      as potential anti-HIV agents. In our laboratory, acacetin-7-O-beta-D
      galactopyranoside (131) from Chrysanthemum morifolium and chrysin (102), as well
      as apigenin-7-O-beta-D-glucopyranoside (130), from Kummerowia striata, have been
      found to exhibit anti-HIV activity. In other studies, some flavonoids and related
      compounds have been investigated as inhibitors of HIV-1 reverse transcriptase,
      protease, and integrase. The isolation and structural modification of such plant
      derived active principles provide a continuing source of potential antitumor and
      anti-HIV agents.

PMID- 9781306
TI  - Inhibition of mammary cancer by citrus flavonoids.
AB  - Double strength orange juice given to the rats in place of drinking water
      inhibited mammary tumorigenesis induced in female Sprague-Dawley rats by DMBA
      more effectively than double strength grapefruit juice. This may mean that
      hesperetin retains its effectiveness in vivo better than naringenin, since the
      flavonoids are present in the juices at similar levels. It is also possible that
      orange juice contains other compounds that have anti-cancer activity and that may
      act synergistically with hesperetin. Citrus flavonoids are effective inhibitors
      of both estrogen receptor-negative MDA-MB-435 and estrogen receptor-positive MCF
      7 human breast cancer cell in vitro. Furthermore, 1:1 combinations of flavonoids
      with tocotrienols and/or tamoxifen inhibit proliferation of the cells more
      effectively than the individual compounds. This synergism may be due to the fact
      that the compounds are exerting their inhibitory effects by different mechanisms.

PMID- 9781307
TI  - Inhibition of neoplastic transformation and bioavailability of dietary flavonoid
      agents.
AB  - Evaluation of unknown biological effects of chemicals including food plant
      products requires the assessment of bioactivity and bioavailability.
      Epidemiologic studies show consistently a cancer protective effect of fruit and
      vegetable consumption, but there is little understanding of which phytochemicals
      account for this observation. Commonly studied antioxidant micronutrients are
      less consistently correlated with cancer protection relative to the food groups
      themselves, suggesting that other phytochemicals or a combination of food
      products play key roles in preventing cancer. We investigated the effects of the
      predominant dietary flavonoids and isoflavonoids at inhibiting neoplastic
      transformation induced by 3-methylcholanthrene in C3H 10T1/2 murine fibroblasts.
      We found that most phenolic agents tested were equal to or superior to known
      chemopreventive agents such as carotenoids or vitamins in effectiveness.
      Hesperetin, hesperidin and catechin were the most potent agents among the
      flavonoids tested, inhibiting transformation completely when applied at 1.0
      microM after exposure to the carcinogen. Structure-activity comparison revealed
      that among the compounds tested, flavonoids with a vicinal diphenol structure in
      ring 'B' and a saturated 'C' ring exhibited the strongest effects. Most agents
      tested showed dose-dependent patterns. Interestingly, the soy isoflavonoids were
      weakly active except when applied in combination, suggesting a synergistic
      effect. In addition, HPLC techniques were developed for determining the
      bioavailability of isoflavonoids in human biological fluids including urine,
      plasma and breast milk. We observed a relatively fast absorption, distribution
      and elimination of isoflavonoids including a biphasic pattern probably due to
      enterohepatic circulation. Total peak isoflavone levels in urine, plasma and in
      breast milk were found to be 60 microM, 2 microM and 0.2 microM, respectively and
      were reached 8-12 hours after consumption of soy foods. Levels detected in human
      body fluids were found to be highly active at inhibiting neoplastic
      transformation, especially considering synergistic effects observed for
      combinations of daidzein and genistein, the predominant isoflavonoids occurring
      in soy foods.

PMID- 9781308
TI  - Flavonoids as hormones. A perspective from an analysis of molecular fossils.
AB  - Although for centuries plants have been known to have hormone-like actions in
      humans, the mechanism(s) by which plant-derived compounds act in humans is still
      being elucidated, a goal that has assumed more importance due to interest in the
      protective actions of fruits and vegetables in diseases such as cancer. Here I
      use the "molecular fossil record" of amino acid sequences of proteins involved in
      regulating the actions steroids, retinoids, thyroid hormone and prostaglandins to
      propose some mechanisms by which flavonoids in fruits and vegetables can have
      hormone-like actions in humans. I focus on: i) hormone receptors that bind to DNA
      and regulate gene transcription and ii) the enzymes that regulate the
      concentrations of these hormones. Comparative analyses of amino acid sequences
      show that nuclear receptors for steroids, retinoids, thyroid hormone and
      prostaglandins in humans and insects are descended from a common ancestor.
      Similar analyses of dehydrogenases that regulate the concentrations of steroids,
      retinoids and prostaglandins reveal strong sequence similarity to enzymes in
      plants, insects, fungi, and bacteria. The similarity is sufficient to suggest
      that some compounds that bind receptors or enzymes in invertebrates, plants or
      unicellular organisms may also bind to mammalian homologs that are involved in
      endocrine physiology. Among the phytochemicals that are candidates for such
      activity are flavonoids because they are involved in plant-insect and plant
      bacteria interactions and have some structural and chemical similarities to
      steroids, retinoids, thyroid hormone, prostaglandins and fatty acids. These
      similarities and the kinship of human, plant, insect and bacterial proteins
      involved in signal transduction provide a conceptual framework for investigating
      flavonoids for hormone-like actions in humans. Understanding these modes of
      action may be useful in developing protocols for preventing hormone-dependent
      diseases such as breast and prostate cancer.

PMID- 9781309
TI  - An overview of muscle glucose uptake during exercise. Sites of regulation.
AB  - The uptake of blood glucose by skeletal muscle is a complex process. In order to
      be metabolized, glucose must travel the path from blood to interstitium to
      intracellular space and then be phosphorylated to glucose 6-phosphate (G6P).
      Movement of glucose from blood to interstitium is determined by skeletal muscle
      blood flow, capillary recruitment and the endothelial permeability to glucose.
      The influx of glucose from the interstitium to intracellular space is determined
      by the number of glucose transporters in the sarcolemma and the glucose gradient
      across the sarcolemma. The capacity to phosphorylate glucose is determined by the
      amount of skeletal muscle hexokinase II, hexokinase II compartmentalization
      within the cell, and the concentration of the hexokinase II inhibitor G6P. Any
      change in glucose uptake occurs due to an alteration in one or more of these
      steps. Based on the low calculated intracellular glucose levels and the higher
      affinity of glucose for phosphorylation relative to transport, glucose transport
      is generally considered rate-determining for basal muscle glucose uptake.
      Exercise increases both the movement of glucose from blood to sarcolemma and the
      permeability of the sarcolemma to glucose. Whether the ability to phosphorylate
      glucose is increased in the working muscle remains to be clearly shown. It is
      possible that the accelerated glucose delivery and transport rates during
      exercise bias regulation so that muscle glucose phosphorylation exerts more
      control on muscle glucose uptake. Conditions that alter glucose uptake during
      exercise, such as increased NEFA concentrations, decreased oxygen availability
      and adrenergic stimulation, must work by altering one or more of the three steps
      involved in glucose uptake. This review describes the regulation of glucose
      uptake during exercise at each of these sites under a number of conditions, as
      well as describing muscle glucose uptake in the post-exercise state.

PMID- 9781310
TI  - Anatomy of glucose transporters in skeletal muscle. Effects of insulin and
      contractions.

PMID- 9781311
TI  - Role of transverse tubules (T-tubules) in muscle glucose transport.
AB  - The first data to demonstrate glucose transporter translocation in muscle used
      membranes enriched in sarcolemma because it was assumed that this was the
      equivalent of the cell membrane of adipocytes. We studied translocation in intact
      human muscle using immunogold labeling of the GLUT4 transporter but found very
      little labeling on the sarcolemma. In contrast, there was abundant gold-labeling
      associated with the T-tubules and we proposed that glucose transport occurred
      across this membrane system. In a subsequent study using an entirely different
      technique, we labeled cell surface glucose transporters of rat muscle with a cell
      impermeant photolabel and demonstrated that a majority of the glucose
      transporters were translocated to T-tubules, not to the sarcolemma, in response
      to insulin. In this report we show for the first time that in insulin-plus
      contraction stimulated muscle, GLUT4 glucose transporters are associated with an
      area that we call the SCT complex (Sarcolemmal, Caveoli, T-tubule complex). This
      SCT complex may play an important role in delivering metabolites to the muscle
      under conditions, such as muscle contraction, when there is a very high
      requirement for glucose transport. From our data, and supporting data from other
      labs, we propose that the T-tubule membrane system plays a very important role in
      delivering nutrients to the center of skeletal muscle cells. Substrates can be
      quickly carried to the center of the muscle fiber where there are proteins to
      transport glucose (and presumably other substrates) across the T-tubule membrane
      to the site where it can be immediately utilized or stored. This hypothesis
      deserves serious consideration and experimental testing.

PMID- 9781312
TI  - GLUT5 expression and fructose transport in human skeletal muscle.
AB  - Biochemical and immunocytochemical studies have revealed that, in addition to
      GLUT1 and GLUT4, human skeletal muscle also expresses the GLUT5 hexose
      transporter. The subcellular distribution of GLUT5 is distinct from that of
      GLUT4, being localised exclusively in the sarcolemmal membrane. The substrate
      selectivity of GLUT5 is also considered to be different to that of GLUT1 and
      GLUT4 in that it operates primarily as a fructose transporter. Consistent with
      this suggestion studies in isolated human sarcolemmal vesicles have shown that
      fructose transport obeys saturable kinetics with a Vmax of 477 +/- 37 pmol.mg
      protein-1 min-1 and a Km of 8.3 +/- 1.2 mM. Unlike glucose uptake, fructose
      transport in sarcolemmal vesicles was not inhibited by cytochalasin B suggesting
      that glucose and fructose are unlikely to share a common route of entry into
      human muscle. Muscle exercise, which stimulates glucose uptake through the
      increased translocation of GLUT4 to the plasma membrane, does not increase
      fructose transport or sarcolemmal GLUT5 content. In contrast, muscle inactivity,
      induced as a result of limb immobilisation, caused a significant reduction in
      muscle GLUT4 expression with no detectable effects on GLUT5. The presence of a
      fructose transporter in human muscle is compatible with studies showing that this
      tissue can utilise fructose for both glycolysis and glycogenesis. However, the
      full extent to which provision of fructose via GLUT5 is important in meeting the
      energy requirements of human muscle during both physiological and
      pathophysiological circumstances remains an issue requiring further
      investigation.

PMID- 9781313
TI  - Snareing GLUT4 at the plasma membrane in muscle and fat.
AB  - Explosive advances in the understanding of vesicle trafficking between
      intracellular compartments have occurred in recent years. These investigations
      inspired an attractive model for intracellular membrane transport, referred as
      the SNARE hypothesis. These advances have been profitably applied to one system
      in muscle and fat; the regulation of intracellular trafficking of the insulin
      regulatable facilitative glucose transporter (GLUT4). Investigations in insulin
      sensitive cell types revealed a remarkable conservation in the mechanism of
      vesicular transport between synaptic vesicles in the presynaptic nerve terminal
      and GLUT4-containing vesicles in muscle and fat. On the other hand, unique
      players in insulin-regulatable GLUT4 movement have also been clarified during
      this process. Thus, unveiling the molecular mechanisms regulating insulin
      stimulated GLUT4 trafficking will significantly contribute to our understanding
      of whole body glucose homeostasis as well as the cell biology of protein
      trafficking, membrane dynamics, and organelle biogenesis.

PMID- 9781314
TI  - Molecular mechanisms involved in GLUT4 translocation in muscle during insulin and
      contraction stimulation.
AB  - Studies in mammalian cells have established the existence of numerous
      intracellular signaling cascades that are critical intermediates in the
      regulation of various biological functions. Over the past few years considerable
      research has shown that many of these signaling proteins are expressed in
      skeletal muscle. However, the detailed mechanisms involved in the regulation of
      glucose transporter (GLUT4) translocation from intracellular compartments to the
      cell surface membrane in response to insulin and contractions in skeletal muscle
      are not well understood. In the present essay we report three different
      approaches to unravel the GLUT4 translocation mechanism: 1. specific pertubation
      of the insulin and/or contraction signaling pathways; 2. characterization of the
      protein composition of GLUT4-containing vesicles with the expectation that
      knowledge of the constituent proteins of the vesicles may help in understanding
      their trafficking; 3. degree of co-immunolocalization of the GLUT4 glucose
      transporters with other membrane marker proteins assessed by immunofluorescense
      and electron microscopy.

PMID- 9781315
TI  - Insulin signaling and glucose transport in insulin resistant skeletal muscle.
      Special reference to GLUT4 transgenic and GLUT4 knockout mice.
AB  - Glucose homeostasis is impaired in patients with non-insulin dependent diabetes
      mellitus (NIDDM) and this defect in due in part, to defects in glucose transport
      in skeletal muscle. Intense interest is now focused on whether reduced insulin
      mediated glucose transport in muscle from NIDDM patients results from alterations
      in the insulin signal transduction pathway or from alterations in traffic and/or
      translocation of GLUT4 to the plasma membrane. Recently, potential targets for
      impaired traffic/translocation of GLUT4 have been reported to include defective
      phosphorylation of IRS-1 and reduced PI-3 kinase activity. In addition to insulin
      signaling defects, impaired glucose transport may result from a defect(s) in the
      activation or functional capacity of GLUT4. Because GLUT4 is dysregulated in
      skeletal muscle from NIDDM patients, it is an attractive target for gene therapy.
      Overexpression of GLUT4 in muscle results in increased glucose uptake and
      metabolism, and protects against the development of insulin resistance in
      transgenic mice. Genetic ablation of GLUT4 results in impaired insulin tolerance
      and defects in glucose metabolism in skeletal muscle. Because impaired muscle
      glucose transport leads to reduced whole body glucose uptake and hyperglycemia,
      understanding the molecular regulation of glucose transport in skeletal muscle is
      necessary to develop effective strategies to prevent or reduce the incidence of
      NIDDM.

PMID- 9781316
TI  - Role of nitric oxide in contraction induced glucose transport.
AB  - Nitric oxide (NO) is a vasoactive substance, which was first described as
      endothelium derived relaxing factor (EDRF). Subsequently, NO has been found to be
      a messenger molecule abundantly present in the nervous system. Functioning as a
      neurotransmitter in the peripheral nervous system, NO mediates an array of
      physiological functions such as gastrointestinal motility, regional blood flow,
      smooth muscle contraction, neuroendocrine activity and immune function. Recently
      NO biosynthesis has been found in skeletal muscle, where NO exerts an effect on
      both the metabolic and contractile processes. This review will focus on the
      actions of NO in skeletal muscle metabolism. NO donors have been shown to
      increase glucose transport in skeletal muscle. Inhibition of NOS activity blunts
      contraction-stimulated glucose transport but has no effect on insulin-stimulated
      glucose transport. NOS protein expression is enhanced by chronic exercise
      suggesting that NO may play a role in the improved glucose tolerance and
      increased insulin sensitivity characteristic of the trained state.

PMID- 9781317
TI  - Role of adenosine in regulation of carbohydrate metabolism in contracting muscle.
AB  - Adenosine production from AMP in the sarcoplasm and interstitial space of muscle
      is markedly enhanced during contractions. The produced adenosine may act as a
      'local hormone' by binding to various types of adenosine receptors present in the
      membrane of adjacent cells, including skeletal muscle, vascular smooth muscle and
      neurons. Thus, interstitial adenosine may significantly contribute to regulation
      of muscle carbohydrate metabolism, both by adjusting metabolism and local blood
      flow to the energy needs imposed by a given degree of contratile activity on the
      muscle cell. The studies presented here demonstrate that endogenous adenosine via
      A1-adenosine receptors is able to directly stimulate insulin-mediated glucose
      transport in oxidative muscle cells during contractions. In addition, adenosine
      may further contribute to stimulation of muscle glucose uptake during
      contractions by increasing blood flow and thereby targetting glucose and insulin
      delivery to active muscle fibres. Furthermore, our findings demonstrate that
      adenosine via A1- and A2-receptors may inhibit glycogen breakdown in oxidative
      muscle tissue which during contractions is simultaneously exposed to insulin and
      beta-adrenergic stimulation. It is concluded that adenosine importantly
      contributes to regulation of carbohydrate metabolism in oxidative muscle fibers
      during contractions.

PMID- 9781318
TI  - Training effects on muscle glucose transport during exercise.
AB  - Muscle glucose uptake is increased during exercise compared to rest. In general,
      muscle glucose uptake increases with increasing exercise intensity and duration.
      Whereas the arterio-venous concentration difference only increases 2-4-fold
      during exercise compared with rest the increase in muscle perfusion in 10-20
      times and therefore quantitatively very important. During exercise the surface
      membrane glucose transport capacity increases in skeletal muscle primarily due to
      an increase in surface membrane GLUT4 protein content. Endurance training
      decreases muscle glucose uptake during exercise at a given absolute submaximal
      work-load despite a large increase in muscle GLUT4 protein content. We have shown
      that this decrease in glucose uptake at least in part is due to a blunted
      exercise-induced increase in sarcolemmal glucose transport capacity secondary to
      a blunted increase in sarcolemmal GLUT4 transporter number. Thus, endurance
      training leads to a marked reduction of the fraction of muscle GLUT4 that is
      translocated during a given submaximal exercise bout. Whether this is true also
      during exercise at higher intensities remains to be seen.

PMID- 9781320
TI  - Insulin sensitivity, muscle fibre types, and membrane lipids.
AB  - One of the key abnormalities of non-insulin-dependent diabetes mellitus (NIDDM)
      and related diseases of the "Metabolic Syndrome" is impaired insulin action
      (insulin resistance). Since skeletal muscle plays a major role in insulin
      stimulated glucose uptake and whole-body energy expenditure, it is a central
      player in carbohydrate and lipid metabolism, and hence in the balance between
      health and disease. This manuscript seeks to describe the evidence both for
      involvement in insulin resistance of three major muscle variables: membrane lipid
      composition, storage triacylglycerol and fibre type mixture; and for the
      interrelationships between these variables. Taken with results provided in other
      chapters in this volume, the literature described gives insights into the role
      that certain dietary fats and physical inactivity may play in the development of
      insulin resistance and hence the disease cluster of the Metabolic Syndrome.

PMID- 9781319
TI  - Hepatic glucose production during exercise.
AB  - Hepatic glucose production increases during exercise as a sum of liver
      glycogenolysis and gluconeogenesis. Whereas the former dominates during intense
      exercise, the latter contributes substantially with prolonged exercise and the
      concomitant decline in liver glycogen stores and with increased gluconeogenic
      precursor supply. Afferent neural feedback signals from contracting muscle and
      feedback signals mediated via the blood stream, can stimulate glucose production
      to maintain euglycemia. A rise in blood glucose directly inhibits hepatic glucose
      production, whereas a decline in blood glucose enhances liver glucose production
      via release of glucoregulatory hormones. In addition to this, central mechanisms
      coupled to the degree of motor center activity can be responsible for part of the
      increase in glucose mobilization, especially during intense exercise where
      hepatic glucose release exceeds peripheral glucose uptake and plasma glucose
      rises. A decline in plasma insulin is important for the rise in glucose
      production during exercise in a variety of species, whereas an increase in plasma
      glucagon is probably more important in other species than man, where glucagon
      plays a role only in prolonged exercise. Sympathetic nervous activity to the
      liver and circulating norepinephrine has been demonstrated to be without any role
      in glucose production, whereas epinephrine has a minor stimulating effect on
      hepatic glucose mobilization during intense exercise. Growth hormone and cortisol
      contribute only minimally to the exercise induced rise in liver glucose output.

PMID- 9781321
TI  - Training induced changes in the fatty acid composition of skeletal muscle lipids.
      Functional aspects.
AB  - Insulin sensitivity relates to the fatty acid composition of the skeletal muscle
      phospholipids and the intramuscular triglyceride content. The fatty acid
      composition of the phospholipids--but not of the triglycerides--in the muscles
      are influenced by regular physical activity of low-moderate intensity. An
      increased degree of unsaturation of the cell membranes after training may
      hypothetically contribute to the improvement of insulin sensitivity. Different
      ways of reducing the supply of lipids in the muscles may possibly cause similar
      changes of the fatty acid composition of the cell membranes. Further studies are
      needed to explore the relationships between changes of the skeletal muscle lipid
      composition during physical activity, the interaction with dietary fat intake,
      and changes of insulin sensitivity and development of related metabolic
      disorders.

PMID- 9781322
TI  - Fat metabolism in exercise.
AB  - Fatty acids are the most abundant source of endogenous energy substrate. They can
      be mobilized from peripheral adipose tissue and transported via the blood to
      active muscle. During higher intensity exercise, triglyceride within the muscle
      can also be hydrolyzed to release fatty acids for subsequent direct oxidation.
      Control of fatty acid oxidation in exercise can potentially occur via changes in
      availability, or via changes in the ability of the muscle to oxidize fatty acids.
      We have performed a series of experiments to distinguish the relative importance
      of these potential sites of control. The process of lipolysis normally provides
      free fatty acids (FFA) at a rate in excess of that required to supply resting
      energy requirements. At the start of low intensity exercise, lipolysis increases
      further, thereby providing sufficient FFA to provide energy substrates in excess
      of requirements. However, lipolysis does not increase further as exercise
      intensity increases, and fatty acid oxidation becomes approximately equal to the
      total amount of fatty acids available at 65% of VO2 max. When plasma FFA
      concentration is increased by lipid infusion during exercise at 85% VO2 max, fat
      oxidation is significantly increased. Taken together, these observations indicate
      that fatty acid availability can be a determinant of the rate of their oxidation
      during exercise. However, even when lipid is infused well in excess of
      requirements during high-intensity exercise, less than half the energy is derived
      from fat. This is because the muscle itself is a major site of control of the
      rate of fat oxidation during exercise. We have demonstrated that the mechanism of
      control of fatty acid oxidation in the muscle is the rate of entry into the
      mitochondria. We hypothesize that the rate of glycolysis is the predominant
      regulator of the rate of carbohydrate metabolism in muscle, and that a rapid rate
      of carbohydrate oxidation caused by mobilization of muscle glycogen during high
      intensity exercise inhibits fatty acid oxidation by limiting transport into the
      mitochondria. During low intensity exercise, glycogen breakdown and thus
      glycolysis is not markedly stimulated, so the increased availability of fatty
      acids allows their oxidation to serve as the predominant energy source. At higher
      intensity exercise, stimulation of glycogen breakdown and glycolysis cause
      increased pyruvate entry into the TCA cycle for oxidation, and as a consequence
      the inhibition of fatty acid oxidation by limiting their transport into the
      mitochondria.

PMID- 9781323
TI  - Mechanisms regulating adipocyte lipolysis.
AB  - Mechanisms regulating adipocyte lipolysis are reviewed in three stages. The first
      stage examines plasma membrane hormone receptors and G-proteins. The primary
      regulators of adipose tissue lipolysis, the catecholamines, bind to the alpha 2,
      beta 1, beta 2, and beta 3 adrenergic receptors. The alpha 2 receptor couples
      with Gi-proteins to inhibit cyclic AMP formation and lipolysis, while the beta
      receptors couple with Gs-proteins to stimulate cyclic AMP formation and
      lipolysis. The beta 1 receptor may mediate low level catecholamine stimulation,
      while the beta 3 receptor, which is activated by higher levels of catecholamines,
      may deliver a more sustained signal. The second stage examines the regulation of
      cyclic AMP, the intracellular messenger that activates protein kinase A. Adenylyl
      cyclase synthesizes cyclic AMP from ATP and is regulated by the G-proteins.
      Phosphodiesterase 3B hydrolyzes cyclic AMP to AMP and is activated and
      phosphorylated by both insulin and the catecholamines norepinephrine and
      epinephrine. The third stage focuses on the rate-limiting enzyme of lipolysis,
      hormone-sensitive lipase (HSL). This 82 to 88 kDa protein is regulated by
      reversible phosphorylation. Protein kinase A activates and phosphorylates the
      enzyme at 2 sites, and 3 phosphatases have been implicated in HSL
      dephosphorylation. The translocation of HSL from the cytosol to the lipid droplet
      in response to lipolytic stimulation may be facilitated by a family of lipid
      associated droplets called perilipins that are heavily phosphorylated by protein
      kinase A and dephosphorylated by insulin. As the mechanisms regulating adipocyte
      lipolysis continue to be uncovered, we look forward to the challenges of
      integrating these findings with research at the in situ and in vivo levels.

PMID- 9781324
TI  - Regulation of fatty acid delivery in vivo.
AB  - Adipose tissue triacylglycerol (TG) constitutes by far the largest energy store
      in the body. In order for this TG to be used as a substrate for oxidative
      metabolism, it has to be exported from adipose tissue and transported to the
      tissues where it will be used. Following hydrolysis of stored TG, non-esterified
      fatty acids (NEFA) leave the adipocyte and enter the plasma. Unlike tissues such
      as skeletal muscle which extract plasma NEFA, in adipose tissue the flow of fatty
      acids across the cell membrane is bi-directional, outward in times of net fat
      mobilization such as fasting and exercise, and inward during the postprandial
      period. Factors regulating NEFA delivery in vivo include hormonal and nervous
      stimulation of lipolysis, and a variety of factors, local and systemic, which
      oppose this by suppressing lipolysis. Adipose tissue blood flow (ATBF) is also
      important. ATBF is increased in states of fat mobilization and fat deposition,
      although there is evidence that during strenuous exercise the increase in ATBF is
      not sufficient for export of all the NEFA made available from lipolysis. There
      are well-documented regional variations in lipolysis. The intra-abdominal depots
      appear to have the highest rates of TG turnover, the subcutaneous abdominal an
      intermediate rate, and the gluteal-femoral depots to have relatively sluggish
      turnover. However, much of the evidence for this derives from studies of isolated
      adipocytes, and confirmation in vivo is much needed. There are links between
      abdominal fat deposition and risk of cardiovascular disease which may be mediated
      through increased fatty acid delivery from abdominal fat depots. The ability of
      exercise specifically to decrease intra-abdominal fat stores may be yet another
      health benefit of regular exercise.

PMID- 9781325
TI  - Transport of long-chain fatty acids across the muscular endothelium.
AB  - Both skeletal and cardiac muscle cells rely heavily on the oxidation of long
      chain fatty acids to utilize chemically stored energy for contractile work. Under
      normal conditions fatty acids are continuously supplied from the microvascular
      compartment to the contracting myocytes. Exogenous fatty acids are transported to
      muscle tissue via the blood either complexed to albumin or covalently bound in
      triacylglycerols forming the neutral lipid core of circulating lipoproteins such
      as chylomicrons or very low-density lipoproteins. The first barrier met by fatty
      acids on their way from the vascular compartment to the myocytes is the
      endothelium constituting the capillary wall. After dissociation of the albumin
      fatty acid complex or release from the triacylglycerol core of lipoproteins,
      fatty acids most likely transverse the endothelium by crossing the luminal
      membrane, the cytosol, and subsequently the abluminal wall of the endothelial
      cell. Transfer through the interendothelial clefts or lateral diffusion within
      the phospholipid bilayer of the endothelial plasmalemma should be considered as
      inconsequential. The mechanism responsible for transmembrane movement of fatty
      acids is incompletely understood, although recent findings suggest the
      involvement of a number of membrane-associated proteins. Kinetic studies have
      revealed that interaction of the albumin-fatty acid complex with the endothelial
      membrane may accelerate the dissociation of the complex, which facilitates the
      uptake of fatty acids by the endothelium. Albumin-binding proteins (ABP) might be
      instrumental in this interaction. Moreover, plasmalemmal fatty acid-binding
      protein (FABPpm), fatty acid translocase (FAT) and fatty acid-transport protein
      (FATP) are putatively involved in transmembrane movement of the fatty acid
      molecules. Diffusion through the endothelial cytosol might be facilitated by a
      cytoplasmic fatty acid-binding protein, the type of which may be related to the
      epithelial fatty acid-binding protein (E-FAPBc).

PMID- 9781326
TI  - Skeletal muscle fatty acid transport and transporters.
AB  - Long-chain fatty acids (LCFAs) are an important energy source for many tissues.
      The dogma that LCFAs are freely diffusible has been challenged. It is now known
      that LCFAs are transported into many tissues. Our studies have shown that LCFAs
      are also transported into skeletal muscle and into the heart. In recent years a
      number of putative fatty acid transport proteins have been identified. These are
      known as plasma membrane fatty acid binding protein (FABPpm, 43 kDa), fatty acid
      translocase (FAT, 88 kDa) and fatty acid transporter protein (FATP, 63 kDa). All
      three proteins are present in skeletal muscle and in the heart. The existence of
      an LCFA transport system in muscle may be essential 1) to facilitate the rapid
      and regulatable transport of LCFA to meet the metabolic requirements of working
      muscles and 2) to cope with an increase in circulating LCFAs in some pathological
      conditions (e.g. diabetes). There is now some evidence that metabolic changes and
      chronically increased muscle activity can increase the transport of LCFAs and
      increase the expression of putative LCFA transporters.

PMID- 9781327
TI  - Intracellular transport of fatty acids in muscle. Role of cytoplasmic fatty acid
      binding protein.
AB  - Long-chain fatty acids represent a major substrate for energy production in
      striated muscles, especially in those muscles which have a high oxidative
      enzymatic capacity. Following their uptake from the extracellular compartment the
      fatty acids have to translocate through the aqueous cytoplasm of the myocytes to
      reach the mitochondria where they undergo oxidative degradation. This
      intracellular transport is assisted by cytoplasmic fatty acid-binding protein
      (FABPc), a small (15 kD) protein which shows a high affinity for the non-covalent
      binding of long-chain fatty acids, and of which several types occur. So-called
      heart-type or muscle-type FABPc is found in muscle cells, and is abundant
      especially in oxidative fibers. The muscular FABPc content appears to relate to
      the rate of fatty acid utilization, and also changes in concert to modulations in
      fatty acid utilization induced by (patho)physiological stimuli (e.g. endurance
      training, diabetes). The facilitation of intracellular fatty acid transport by
      FABPc is accomplished by increasing the concentration of the diffusing fatty
      acids in the aqueous cytoplasm and, most likely, also by interacting directly
      with membranes to promote transfer of fatty acids to and from the cytosolic
      binding protein.

PMID- 9781328
TI  - Hormone-sensitive lipase (HSL) expression and regulation in skeletal muscle.
AB  - Because the enzymatic regulation of muscle triglyceride metabolism is poorly
      understood we explored the character and activation of neutral lipase in muscle.
      Western blotting of isolated rat muscle fibers demonstrated expression of hormone
      sensitive lipase (HSL). In incubated soleus muscle epinephrine increased neutral
      lipase activity by beta-adrenergic mechanisms involving cyclic AMP-dependent
      protein kinase (PKA). The increase was paralleled by an increase in glycogen
      phosphorylase activity and could be abolished by antiserum against HSL.
      Electrical stimulation caused a transient increase in activity of both neutral
      lipase and glycogen phosphorylase. The increase in lipase activity during
      contractions was not influenced by sympathectomy or propranolol. Training
      diminished the epinephrine induced lipase activation in muscle but enhanced the
      activation as well as the overall concentration of lipase in adipose tissue. In
      agreement with the in vitro findings, in adrenalectomized patients an increase in
      muscle neutral lipase activity was found at the end of prolonged exercise only if
      epinephrine was infused. In accordance with feedforward regulation of substrate
      mobilization in exercise, our studies have shown that HSL is present in skeletal
      muscle cells and is stimulated in parallel with glycogen phosphorylase by both
      epinephrine and contractions. HSL adapts differently to training in muscle
      compared with adipose tissue.

PMID- 9781329
TI  - Training and fatty acid metabolism.
AB  - Older studies in humans seem to suggest a correlation between plasma long chain
      fatty acid (LCFA) turnover and oxidation on the one hand and plasma LCFA
      concentration on the other hand during submaximal exercise. However, recent
      studies in man, in which higher concentrations of plasma LCFA have been reached
      during prolonged submaximal exercise, have revealed a levelling off in net uptake
      in spite of increasing plasma LCFA concentrations. Furthermore, this relationship
      between plasma LCFA concentration and plasma LCFA uptake and oxidation was
      altered by endurance training such that levelling off was not apparent in the
      trained state. These recent findings in man give support to the notion from other
      cell types that transport of fatty acids from the vascular compartment to the
      cytosolic space in the muscle cell is not only due to simple diffusion, but is
      predominantly carrier-mediated. During prolonged submaximal knee-extension
      exercise it has been demonstrated that the total oxidation of LCFA was
      approximately 60% higher in trained compared to nontrained subjects. The training
      induced adaptations responsible for this increased utilization of plasma fatty
      acids by the muscle could be located at several steps from the mobilization of
      fatty acids to skeletal muscle metabolism in the mitochondria. To what extent
      triacylglycerol located in the muscle cell contribute to the overall lipid
      utilisation during exercise is still not clear. However, due to underestimation
      of the contribution of plasma LCFA and fatty acids liberated from the circulating
      VLDL-triacylglycerols to the overall fatty acid oxidation during exercise there
      is increasing understanding that muscle triacylglycerol contributes to a lesser
      extent as fuel during exercise in man than mostly stated.

PMID- 9781330
TI  - Intramuscular mechanisms regulating fatty acid oxidation during exercise.
AB  - Fatty acid oxidation increases in response to exercise, but at high intensities
      the contribution of fatty acid oxidation to energy production decreases. The
      carnitine palmitoyl transferase (CPT) complex appears to be a plausible site of
      regulation of fatty acid oxidation at rest and during exercise. Muscle malonyl
      CoA, a potent inhibitor of CPT I, decreases during muscle contraction as a
      consequence of phosphorylation and inactivation of acetyl-CoA carboxylase (ACC)
      by AMP-activated protein kinase (AMPK). When AMPK is artificially activated with
      AICA riboside, ACC is inactivated, malonyl-CoA decreases, and fatty acid
      oxidation increases. Factors other than the muscle malonyl-CoA concentration are
      likely responsible for the decline in fatty acid oxidation during exercise at
      high intensities.

PMID- 9781331
TI  - Regulation of fat/carbohydrate interaction in human skeletal muscle during
      exercise.
AB  - There has been continued interest in the regulation of fat and carbohydrate
      utilization in muscle tissue, as they are the main substrates for energy
      production during exercise in well fed humans. Many investigations have
      demonstrated that increasing fat availability increases fat oxidation and
      decreases carbohydrate use in the whole body and skeletal muscle. However, little
      work has been performed in skeletal muscle to identify the mechanisms, and
      specific biochemical signals which mediate these shifts in fuel selection. The
      classic work in this area, using contracting heart and resting diaphragm muscle,
      led to a theory that could explain reciprocal changes in fat and carbohydrate use
      from a biochemical perspective (glucose-fatty acid cycle). Using this
      information, we embarked on a number of studies demonstrating that the
      biochemical regulation of fat/carbohydrate interaction in human skeletal muscle
      during exercise is different than exists in the continually active heart and
      diaphragm muscles. By increasing the availability of free fatty acids to the
      working muscles, it was demonstrated that carbohydrate downregulation during
      moderate and intense aerobic exercise occurred mainly at glycogen phosphorylase,
      the enzyme that regulates the degradation of muscle glycogen. There was also
      coordinate downregulation of pyruvate dehydrogenase activity at low and moderate
      exercise intensities. We have also investigated the roles that carnitine
      palmitoyl-transferase I and its regulator malonyl-CoA play in governing the
      transport of long-chain fatty acids into the mitochondria for oxidation, and
      therefore the impact on carbohydrate use in human skeletal muscle. The regulation
      of Carnitine Palmitoyltransferase I (CPTI) activity appears to involve more than
      changes in the concentration of malonyl-CoA. Several additional mechanisms may
      exist that interact with or override the effects of malonyl-CoA during exercise,
      although this work is just beginning. The present work has identified several
      regulatory sites in the pathways of carbohydrate and fat metabolism that help
      explain the regulation of fat/carbohydrate interaction in human skeletal muscle
      during exercise.

PMID- 9781332
TI  - Malonyl CoA as a metabolic switch and a regulator of insulin sensitivity.
AB  - Malonyl CoA is a regulator of carnitine palmitoyl transferase 1 (CPT1), the
      enzyme that controls the transfer of long chain fatty acyl CoA into mitochondria
      where it is oxidized. Recent studies indicate that in skeletal muscle the
      concentration of malonyl CoA is acutely (minutes) regulated by changes in its
      fuel supply and energy expenditure. In response to changes in fuel supply,
      regulation appears to be due to alterations in the cytosolic concentration of
      citrate, which is both an allosteric activator of acetyl CoA carboxylase (ACC),
      the enzyme that catalyzes malonyl CoA synthesis and a source of its precursor,
      cytosolic acetyl CoA. During exercise and immediately thereafter regulation by
      citrate appears to be lost and malonyl CoA levels diminish as the result of a
      decrease in ACC activity secondary to phosphorylation. Sustained increases in the
      concentration of malonyl CoA have been observed in muscle of a number of insulin
      resistant rodents including the Zucker (fa/fa) and GK rats, KKAgy mice, glucose
      infused rats and rats in which muscle has been made insulin resistant by
      denervation. Available data suggest that malonyl CoA could be linked to insulin
      resistance in these rodents by virtue of its effects on the cytosolic
      concentration of long chain fatty acyl CoA (LCFA CoA) and one or more protein
      kinase C isozymes. Whether similar alterations occur in other tissues and
      contribute to the pathophysiology of the insulin resistance syndrome remains to
      be determined.

PMID- 9781333
TI  - Anaplerosis of the tricarboxylic acid cycle in human skeletal muscle during
      exercise. Magnitude, sources, and potential physiological significance.
AB  - In comparison to cardiac tissue, relatively few data are available regarding the
      concentrations of tricarboxylic acid cycle intermediates (TCAI) and the potential
      influence of TCAI pool size on the regulation of cycle flux in mammalian skeletal
      muscle. However, recent human exercise studies have confirmed the fundamental
      observation made in electrically-stimulated rodent muscle that moderate to
      intense contraction results in a net accumulation of TCAI. The increase in TCAI
      pool size, termed "anaplerosis," appears exponentially related to work intensity,
      although the relative changes in the individual cycle intermediates differ
      markedly. While a number of mechanisms could potentially contribute to the
      increase in TCAI, the reaction catalyzed by alanine aminotransferase appears
      primarily responsible for anaplerosis at the onset of exercise in humans. The
      expansion of the TCAI pool has been suggested to be important for aerobic energy
      provision, and various theories have been proposed which link the total
      concentration of TCAI with the capacity for TCA cycle flux during exercise.
      However, despite the recent advances which have been made with regard to the
      magnitude and potential source of TCAI expansion in humans, our understanding of
      the physiological significance of anaplerosis is limited. Indeed, it remains
      speculative whether the increase in TCAI pool size represents an important
      regulatory signal or is simply a consequence of the huge increase in metabolic
      flux which occurs during exercise.

PMID- 9781334
TI  - Pyruvate dehydrogenase complex activation status and acetyl group availability as
      a site of interchange between anaerobic and oxidative metabolism during intense
      exercise.
AB  - During high intensity muscular contraction ATP is supplied at near maximal rates
      by PCr degradation and glycolysis. However, as exercise duration increases, the
      contribution of anaerobic ATP turnover to energy delivery declines due to the
      depletion of PCr stores and a reduction in the rate of glycogenolysis, which
      together may be responsible for the parallel reduction in muscle force production
      and power output. The importance of oxidative phosphorylation to total ATP
      production during intense muscle contraction has been underestimated to date.
      Recent studies have, however, demonstrated that the reduction in work production
      during repeated bouts of maximal exercise is less than the reduction observed in
      anaerobic energy provision. This observation has been suggested to reflect an
      increased contribution from oxidative phosphorylation to total energy production;
      but the mechanism responsible for this increased contribution is poorly
      understood. Recent evidence has pointed to the activation status of the pyruvate
      dehydrogenase complex and/or acetyl group availability as being focal in
      dictating temporal changes in ADP flux at the onset of intense exercise and,
      hence, the relative contribution made by anaerobic and oxidative ATP regenerating
      pathways under these conditions. As might be expected, therefore, maximising the
      contribution from oxidative ATP regeneration at the onset of exercise (by
      pharmacologically activating the pyruvate dehydrogenase complex prior to
      exercise) has been shown to have substantial functional benefits during high
      intensity contraction. This body of work has also illustrated that, contrary to
      popular theory, a large proportion of muscle lactate accumulation at the onset of
      exercise is associated with a lag in the activation of oxidative ATP production
      rather than with a lag in oxygen delivery.

PMID- 9781335
TI  - Amino acid transport during muscle contraction and its relevance to exercise.
AB  - The functional significance of amino acid transport in skeletal muscle has been
      explored by the use of a variety of techniques including work in isolated
      perfused organs, isolated incubated organs and tissue culture of muscle cells.
      The results suggest that although there is a wide variety of amino acid transport
      systems of different characteristics and with different responses to ionic,
      hormonal and nervous modulation, the amino acid glutamine (transported by system
      Nm) demonstrates some unusual properties not observed with amino acids
      transported by other systems. Glutamine is transported at very high rates in
      skeletal muscle and heart and both the glutamate and glutamine transporter appear
      to be adaptively regulated by the availability of glutamine. Glutamine appears to
      be involved in the regulation of a number of important metabolic processes in
      heart and skeletal muscle (e.g., regulation of the glutathione reduced/oxidised
      ratio and regulation of protein and glycogen synthesis). Furthermore, glutamine
      transport appears to interact with systems for regulation of volume control and
      many of the metabolic features attributable to changes in glutamine concentration
      appear to be modulated via alteration in cytoskeletal status.

PMID- 9781336
TI  - Protein and amino acid metabolism in human muscle.
AB  - Muscle proteins turn over slowly and there are minimal diurnal changes in the
      size of the muscle protein pool in response to feeding and fasting. Nitrogen
      balance and tracer studies indicate that protein oxidation and net protein
      breakdown (degradation--synthesis) is not increased during dynamic exercise at
      intensities of < or = 70% VO2max. An imbalance between muscle protein synthesis
      and degradation does exist during one leg knee extensor exercise and during two
      legged cycling in patients with glycogen phosphorylase deficiency. In these
      latter cases amino acids liberated from the protein pool are used for synthesis
      of TCA-cycle intermediates and glutamine. Six amino acids are metabolized in
      resting muscle: leucine, isoleucine, valine, asparagine, aspartate and glutamate.
      Only leucine and part of the isoleucine molecule can be converted to acetylCoA
      and oxidized. The carbon skeleton of the other amino acids is used for synthesis
      of TCA-cycle intermediates and glutamine. The six amino acids provide the amino
      groups and the ammonia for synthesis of glutamine and alanine, which are released
      by muscle in excessive amounts. About half of the glutamine release from muscle
      originates from glutamate taken up from the blood. Glutamine produced by muscle
      is an important fuel and regulator of DNA and RNA synthesis in mucosal cells and
      immune system cells and fulfils several other important functions in human
      metabolism. The alanine aminotransferase reaction functions to establish and
      maintain high concentrations of TCA-cycle intermediates and a high TCA cycle flux
      in the first minutes of exercise. A gradual increase in leucine oxidation
      subsequently leads to a carbon drain on the TCA-cycle in glycogen depleted
      muscles and may thus reduce the maximal flux in the TCA-cycle and lead to
      fatigue. Deamination of amino acids and glutamine synthesis present alternative
      anaplerotic mechanisms in glycogen depleted muscles but only allow exercise at 40
      50% of Wmax. It is proposed that the maximal flux in the TCA-cycle is reduced in
      glycogen depleted muscles due to insufficient TCA-cycle anaplerosis and that this
      presents a limitation for the maximal rate of fatty acid oxidation. Interactions
      between the amino acid pool and the TCA-cycle thus seem to play a central role in
      the energy metabolism of the exercising muscle.

PMID- 9781337
TI  - Three-dimensional structure of lactoferrin. Implications for function, including
      comparisons with transferrin.

PMID- 9781338
TI  - Structures of buffalo and mare lactoferrins. Similarities, differences, and
      flexibility.

PMID- 9781339
TI  - Direct detection and quantitative determination of bovine lactoferricin and
      lactoferrin fragments in human gastric contents by affinity mass spectrometry.
AB  - Lactoferricin (Lfcin) is a bioactive fragment of lactoferrin derived from the
      bactericidal and putative lymphocyte receptor binding domain(s) located within
      the N-lobe of lactoferrin. Although known to be liberated from at least three
      species of lactoferrin, conditions leading to Lfcin generation in vivo and
      factors affecting its distribution are still not known. Recently, we have
      developed a method of surface-enhanced laser desorption/ionization (SELDI)
      affinity mass spectrometry using n-butyl terminal groups for surface-enhanced
      affinity capture (SEAC) to quantify not only Lfcin generated in vivo but also
      other lactoferrin fragments. Unlike previous efforts to detect lactoferrin and
      Lfcin with specific antibodies, the SELDI affinity assay distinguished
      lactoferrin, lactoferrin fragments, Lfcin and unrelated peptides without their
      interference with each other. To evaluate Lfcin generation in vivo, the
      experimental design involved feeding 200 mL of 10 mg/mL (1.22 x 10(-4) mol/L)
      bovine lactoferrin to an adult. Gastric contents were recovered 10 min after
      ingestion. Lfcin produced in vivo was directly captured by the SEAC device. The
      amount of Lfcin in the gastric contents was 16.91 +/- 2.65 micrograms/mL (5.350
      +/- 0.838 x 10(-6) mol/L). However, a large proportion of the ingested
      lactoferrin was not completely digested. Lactoferrin fragments containing the
      Lfcin region were analyzed by in situ hydrolysis with pepsin after being captured
      by the SEAC device. As much as 5.740 +/- 0.702 x 10(-5) mol/L of the partially
      degraded lactoferrin fragments were found to contain the Lfcin region, including
      peptide domains 17-43, 17-44, 12-44, 9-58, and 16-76 of bovine lactoferrin. These
      results show that bovine Lfcin can be produced in the human stomach after
      ingestion of an infant formula supplemented with bovine lactoferrin. It is now
      important to determine whether Lfcin is generated in the intestinal tract of
      formula-fed and breast-fed infants, and geriatric patients consuming foods
      enriched with lactoferrin.

PMID- 9781340
TI  - Analysis of bovine lactoferrin in whey using capillary electrophoresis (CE) and
      micellar electrokinetic chromatography (MEKC).

PMID- 9781341
TI  - Structural and immunochemical studies on bovine lactoferrin fragments.

PMID- 9781342
TI  - Role of the first N-terminal basic cluster of human lactoferrin (R2R3R4R5) in the
      interactions with the Jurkat human lymphoblastic T-cells.
AB  - We previously characterized a receptor of Mr 105,000 for human lactoferrin (hLf)
      on Jurkat human lymphoblastic T-cells. To delineate the role of R2R3R4R5 of hLf
      in the interaction with cells, we studied the binding of hLf variants obtained
      either by tryptic proteolysis (hLf-2N, hLF-3N and hLf-4N) or by mutagenesis (rhLf
      5N). Consecutive removal of N-terminal arginine residues from hLf progressively
      increased the binding affinity but decreased the number of binding sites on the
      cells. The binding parameters of bovine Lf and native hLf did not differ, whereas
      the binding parameters of murine Lf resembled those of rhLf-5N. Culture of Jurkat
      cells in the presence of chlorate, which inhibits sulfation, reduced the number
      of binding sites for both native hLf and hLf-3N but not for rhLf-5N indicating
      that the hLf binding sites include sulfated molecules. The results suggest that
      the interaction of hLf with about 80,000 binding sites per Jurkat cell, mainly
      sulfated molecules, is dependent on R2R3R4, but not on R5. Interaction with about
      20,000 binding sites per cell, presumably the hLf receptor, does not require the
      first N-terminal basic cluster of hLf. We conclude that the deletion of R2-R5
      from hLf may serve to modulate the nature of its binding to cells and thereby its
      effects on cellular physiology.

PMID- 9781343
TI  - Glycation ligand binding motif in lactoferrin. Implications in diabetic
      infection.
AB  - Lactoferrin and lysozyme are two important, naturally occurring antibacterial
      proteins found in saliva, nasal secretions, milk, mucus, serum and in the
      lysosomes of neutrophils and macrophages. Both proteins bind specifically to
      glucose-modified proteins bearing advanced glycation endproducts (AGEs). Exposure
      to AGE-modified proteins blocks the bacterial agglutination and bacterial killing
      activities of lactoferrin and also inhibits the bactericidal and enzymatic
      activity of lysozyme. Peptide mapping by AGE ligand blot revealed two AGE-binding
      domains in lactoferrin, and a single AGE-binding domain in lysozyme. None of
      these AGE-binding domains displayed any significant homology in their primary
      sequences; however, a common 17-18 amino acid cysteine loop motif (CX15-16C) was
      identified among them, which we named an ABCD motif (AGE-Binding Cysteine-bounded
      Domain). Similar domains are also present in other antimicrobial proteins such as
      defesins. Hydrophilicity analysis indicated that each of these ABCD loops is
      markedly hydrophilic. Synthetic peptides, corresponding to these motifs in
      lactoferrin and lysozyme, exhibited AGE-binding activity. Since diabetes is
      associated with abnormally high levels of tissue and serum AGEs, the elevated
      AGEs may inhibit endogenous antibacterial proteins by binding to the conserved
      ABCD motif, thereby increasing susceptibility to bacterial infections in diabetic
      individuals. These results may provide a basis for the development of new
      approaches to prevent diabetic infections.

PMID- 9781344
TI  - Mouse lactoferrin gene. Promoter-specific regulation by EGF and cDNA cloning of
      the EGF-response-element binding protein.
AB  - Expression of the lactoferrin gene in a variety of tissues is regulated
      differentially. We have previously demonstrated that the lactoferrin gene is
      regulated by estrogen and mitogen in mouse uterus. The mouse lactoferrin gene
      responded to forskolin, cAMP, TPA and EGF stimulation via two adjacent enhancer
      elements, the CRE and EGFRE and collectively referred to as the Mitogen Response
      Unit (MRU). We found that CRE is responsible for forskolin, cAMP and TPA whereas
      EGFRE is for EGF stimulation. We examined the minimal promoter and enhancer
      elements of the mouse lactoferrin gene that are required for EGF induced
      transcriptional activation. We found that the CRE and noncanonical TATA box
      (ATAAA) are the minimal promoter elements for basal activity of the CAT reporter
      construct, whereas, the EGFRE is needed for an additional activity induced by EGF
      in transiently transfected human endometrial carcinoma RL95-2 cells (RL95-2). The
      EGFRE, however, did not function in heterologous promoters (SV 40 and TK).
      Therefore, EGF-stimulated lactoferrin gene activity is promoter specific in RL95
      2 cells. Mutation made at either elements or insertion of extra nucleotides
      between the two elements, severely affected EGF-stimulated activity. Nuclear
      protein prepared from RL95-2 cells protected the EGFRE, CRE and noncanonical TATA
      from DNAase I digestion in a footprinting analysis. Nuclear protein which
      interacted with the CRE were previously identified as API and CREB. In this
      study, we isolated a cDNA clone from an RL95-2 expression library that encodes
      the EGFRE binding protein. Partial sequence of the cDNA clone revealed 100%
      nucleotide identity with a GC-box binding protein, BTEB2. Protein-protein
      interaction among the transcription factors could fine-tune the mouse lactoferrin
      expression in various tissues.

PMID- 9781345
TI  - Cloning of human genomic lactoferrin sequence and expression in the mammary
      glands of transgenic animals.

PMID- 9781346
TI  - Expression of human lactoferrin in transfected rat mammary epithelial cells.

PMID- 9781347
TI  - Restricted spatiotemporal expression of lactoferrin during murine embryogenesis.
AB  - Lactoferrin is a member of the transferrin family of iron-binding proteins to
      which several physiological functions have been ascribed. While there is a wealth
      of evidence about the distribution and function of this protein in the adult, the
      expression and function, if any, of lactoferrin during embryogenesis has not been
      investigated. In the current study, the spatiotemporal distribution of
      lactoferrin was analyzed during normal murine embryonic development. This
      analysis demonstrated that lactoferrin is expressed in three distinct patterns
      during embryogenesis. First, lactoferrin is expressed at the 2-cell stage in the
      preimplantation embryo where it continues to be expressed until the blastocyst
      stage when expression ceases. The second phase of lactoferrin expression is not
      detected until the latter half of gestation when the protein is detected in the
      myeloid cells, beginning in the fetal liver at embryonic day 11 and later in the
      spleen and bone marrow coinciding with the onset and diversification of
      myelopoiesis in these organs during embryogenesis. Finally, lactoferrin is
      detected in a variety of glandular epithelial cells and/or their secretions,
      including respiratory and oral epithelia which is consistent with the expression
      pattern observed for this protein in the adult where it plays an important role
      in host defense at the mucosal surface. Taken together, these analyses indicate
      that the role of lactoferrin in the developing embryo is restricted to the
      preimplantation stage and development of first and second line host defense
      systems.

PMID- 9781348
TI  - Construction of recombinant chimeric human lactoferrin/bovine transferrins.

PMID- 9781349
TI  - The LDL-receptor family. Lactoferrin and lipid metabolism.

PMID- 9781350
TI  - Identification and analysis of a CA(2+)-dependent lactoferrin receptor in rat
      liver. Lactoferrin binds to the asialoglycoprotein receptor in a galactose
      independent manner.
AB  - We identified a 45 kDa Ca(2+)-dependent Lf binding protein on rat hepatocytes.
      Dithiobis(sulfosuccimidylproprionate) (DTSSP)-crosslinked 125I-Lf to a 45 kDa
      adduct in a Ca(2+)-dependent manner on intact cells. The 125I-labeled crosslinked
      complexes were absent when either surface-bound 125I-Lf was stripped prior to
      crosslinking or an excess of unlabeled Lf was included in the DTSSP reaction.
      Triton X-100 extracts of hepatocyte membrane ghosts were chromatographed on Lf
      agarose, and a 45 kDa polypeptide (p45) was eluted by EGTA. Anti-p45 sera blocked
      vigorously 125I-Lf endocytosis to intact rat hepatocytes, confirming that p45
      functions as the Ca(2+)-dependent Lf receptor on hepatocytes. Two tryptic
      fragments of p45 showed 100% identity with internal sequences (Leu121-->Lys126
      and Phe198-->Lys220) of the major subunit (RHL-1) of the rat asialoglycoprotein
      receptor. Antisera against p45 and RHL-1 crossreacted equally well with each
      protein, and asialoorosomucoid blocked the binding of 125I-Lf to hepatocytes. We
      did not detect the minor subunits (RHL-2/3) of the rat asialoglycoprotein
      receptor in p45 preparations from Triton X-100-extracts of hepatocytes, and 125I
      Lf bound to immobilized RHL-1 but not to RHL-2/3. Exoglycosidases were used to
      remove terminally-exposed NeuNAc and alpha- and beta-Gal from bovine Lf glycans,
      and lectin blotting confirmed that glycosidase-treated Lfs lacked detectable
      terminal Gal. Unexpectedly, deglycosylated Lf exhibited no loss in its ability to
      compete with unmodified Lf for binding to isolated hepatocytes. Moreover, beta
      lactose but not sucrose competed vigorously for 125I-Lf endocytosis by
      hepatocytes, indicating that Lf binds at or near the carbohydrate-recognition
      domain of RHL-1. We conclude that RHL-1 is the Ca(2+)-dependent Lf receptor on
      hepatocytes and that it binds Lf in a Gal-independent manner.

PMID- 9781351
TI  - Bacterial lactoferrin receptors.
AB  - Lactoferrin is thought to play a pivotal role in prevention of infection in the
      host and its ability to sequester iron from potential pathogens has been
      considered an important component of its antimicrobial function. A number of
      bacterial species in the Neisseriaceae have developed a mechanism for acquiring
      iron directly from this host glycoprotein which involves surface receptors
      capable of specifically binding lactoferrin. Initial attempts at identifying the
      receptor proteins in Neisseria and Moraxella species using affinity isolation
      with immobilized lactoferrin under high stringency conditions presumptively
      identified a single 100 kDa receptor protein, LbpA (formerly Lbp1). Under
      modified affinity isolation conditions a second 84 kDa lactoferrin binding
      protein was isolated and had been presumptively identified as LbpB. This protein
      was not isolated from a CopB-ve isogenic mutant of Moraxella catarrhalis,
      indicating that it was in fact CopB. However, another lactoferrin binding protein
      isolated under high stringency conditions, that comigrated with LbpA in most, but
      not all, M. catarrhalis strains, was identified by convalescent antisera. Its
      biochemical properties suggested that it indeed was LbpB. The identity of these
      proteins was confirmed by preparing isogenic mutants with the lbpA and lbpB
      genes. Growth studies with isogenic mutants deficient in LbpB, LbpA, CopB or FbpA
      were performed to evaluate their role in iron acquisition from lactoferrin. LbpA
      and FbpA were essential for this process, supporting prior models of the iron
      acquisition pathway. LbpB was not essential which is remniscent of studies with
      the bacterial transferrin receptors. The isogenic CopB-ve isogenic mutants were
      deficient in iron acquisition from both transferrin and lactoferrin, suggesting
      that it is a key component in both pathways. A model providing an alternate
      explanation of the data is presented. The role and surface accessibility of the
      lactoferrin receptor proteins suggests that they might be useful vaccine antigens
      and the preferentially reactivity of convalescent antisera with LbpB suggests
      that it may be the prime candidate.

PMID- 9781352
TI  - Evidence for the existence of a surface receptor for ferriclactoferrin and
      ferrictransferrin associated with the plasma membrane of the protozoan parasite
      Leishmania donovani.
AB  - Previous work has demonstrated the ability of the promastigote form of the
      protozoan parasite Leishmania chagasi to utilize iron chelated to lactoferrin and
      transferrin for growth and metabolism. We have obtained evidence suggesting that
      the promastigote form of the parasite possesses specific binding sites for
      lactoferrin and transferrin. Lactoferrin binding appears to be: 1) independent of
      whether or not the protein contains iron; 2) not inhibited by transferrin; and 3)
      independent of whether the organism is in log or stationary phase of growth.
      Transferrin binding is: 1) markedly greater if the protein is iron loaded; 2)
      inhibited by the presence of lactoferrin; and 3) independent of whether the
      organism is in log or stationary growth phase. Preliminary ligand blot analyses
      are consistent with the presence of a protein or proteins which bind lactoferrin
      and/or transferrin. The relationship to these binding sites to those described in
      other protozoan species requires further investigation.

PMID- 9781353
TI  - Lactoferrin secretion into mouse milk. Development of secretory activity, the
      localization of lactoferrin in the secretory pathway, and interactions of
      lactoferrin with milk iron.

PMID- 9781354
TI  - Lactoferrin in duodenal aspirates during childhood.

PMID- 9781355
TI  - Iron in synovial fluid. Removal by lactoferrin and relationship to iron
      regulatory protein (IRP) activity.

PMID- 9781356
TI  - The gut. A key metabolic organ protected by lactoferrin during experimental
      systemic inflammation in mice.
AB  - The gastrointestinal tract may be viewed as an ecologic system in which a balance
      between the host and bacterial flora exists. Two major host components appear to
      be involved in maintaining this balance. The first is a non-specific structural
      barrier provided by the epithelial layer of the gastrointestinal mucosae. The
      second component involves functional immunological elements found in the mucosal
      and submucosal compartments, e.g., gut associated lymphoid tissue. When gut
      integrity is disrupted by invasive pathogens or by trauma, a myriad of pro
      inflammatory mediators are released from cells in the gut wall that exert actions
      in the tissue or gut lumen. One of these mediators is lactoferrin, and iron
      binding protein found in high concentration in most human exocrine secretions.
      Despite controversies on its physiological role, evidence is emerging that
      lactoferrin plays an important role in host defense against toxic metabolites and
      antigenic components of potential pathogens2-4. This manuscript is intended to
      provide an overview of work related to lactoferrin's modulatory roles in
      inflammation, and to present observations from experimental studies on the
      preservation of intestinal structure and function by lactoferrin during
      intestinal inflammation. The possibility that lactoferrin limits the
      autodestructive inflammatory responses presents a new alternative for the future
      management of systemic inflammation.

PMID- 9781358
TI  - Host defensive effects of orally administered bovine lactoferrin.

PMID- 9781357
TI  - The antibacterial activity of lactoferrin and neonatal E. coli infections. A
      selective and critical review.

PMID- 9781359
TI  - Antiviral activity of lactoferrin.

PMID- 9781360
TI  - Lactoferrin. Antiviral activity of lactoferrin.
AB  - A series of native and chemically derivatized lactoferrins (Lfs) purified from
      milk and colostrum were assayed in vitro for their anti-HIV and anti-HCMV
      cytopathic effects in MT4 cells and fibroblasts respectively. All Lfs from bovine
      and human milk or colostrum were able to completely block HCMV replication as
      well as inhibited HIV-1 induced cytopathic effects. Through acylation of the
      amino function of the lysine residues in Lf, using anhydrides of succinic acid or
      cis-aconitic acid, negatively charged Lf derivatives were obtained that all
      showed a strong antiviral activity against the HIV-1 in vitro. Acylated-Lf
      exhibited a 4-fold stronger antiviral effect on HIV-1 than the parent compound
      but the activity on HCMV was abolished. Peptide scanning studies indicated that
      the native Lf as well as acylated Lf strongly bind to the V3 domain of the HIV
      envelope protein gp120, with Kd values in the same concentration range as the in
      vitro IC50. Therefore, shielding of this domain, resulting in inhibition of the
      virus-cell fusion and entry of the virus in MT4 cells is the likely mechanism
      underlying the anti-HIV activity. In contrast, addition of positive charges to Lf
      through amination of the proteins resulted in an increased anti-HCMV activity and
      a loss of anti-HIV activity, with anti-HCMV IC50 values in the low micromolar
      concentration range. The N-terminal portion of LF appeared essential to this anti
      HCMV effect. The specific distribution of positively and negatively charged
      domains in the molecule appears to be important in both the anti-HIV and anti
      HCMV effects.

PMID- 9781361
TI  - A helical region on human lactoferrin. Its role in antibacterial pathogenesis.
AB  - Human lactoferrin contains a 47 amino acid peptide, named lactoferricin H, which
      is thought to be responsible for its antimicrobial activity. Lactoferricin
      includes a loop region, which resides on the outer surface of the N-lobe of
      lactoferrin, adopting an alpha helix with a hydrophobic tail. Peptides have been
      synthesised corresponding to the highly charged alpha helix (HLP 2) and
      hydrophobic tail region (HLP 5). HLP 2 has potent antibacterial activity whereas
      HLP 5 had no activity. To investigate the relationship between structure and
      function of HLP 2, HLP 6 was synthesised with a proline replacing methionine.
      This substitution was predicted to disrupt the helical region of the peptide and
      the orientation of the positively charged residues. Antibacterial activity was
      significantly reduced when tested against Escherichia coli serotype 0111, NCTC
      8007. The mode of action of HLP 2 against the bacterial membrane was investigated
      by flow cytometric analysis, using Escherichia coli, NCTC 8007. Membrane
      potential and integrity were monitored using the fluorescent probes, bis 1,3
      (dibutylbarbituric acid) trimethine oxonol and propidium iodide respectively. HLP
      2 caused complete loss of membrane potential and integrity, with irreversible
      damage to the cell as shown by rapid loss of viability. We conclude that HLP 2
      causes membrane disruption and that helicity is an important factor for
      antibacterial activity.

PMID- 9781362
TI  - Interaction of lactoferrin with Micrococcus spp. and its role in antimicrobial
      activity.

PMID- 9781363
TI  - Enhanced anti-Candida activity of neutrophils and azole antifungal agents in the
      presence of lactoferrin-related compounds.
AB  - We investigated the effects of lactoferrin (Lf)-related compounds on growth
      inhibition of Candida albicans by neutrophils or antifungal agents in vitro.
      Human neutrophils partially inhibited the growth of C.albicans. The growth
      inhibition caused by human neutrophils was augmented by the addition of human Lf
      at concentrations which did not show any inhibitory effect in the absence of
      neutrophils. Similar observations were obtained also with the following
      combinations: human neutrophils + bovine Lf, murine neutrophils + bovine Lf, and
      murine neutrophils + iron saturated bovine Lf, but not in the case of murine
      neutrophils + human transferrin. The minimum inhibitory concentration (MIC) of
      azole antifungal agents, clotrimazole, ketoconazole, fluconazole, and
      itraconazole was reduced by 1/4 to 1/16 in the presence of a sub-MIC level of
      each of bovine Lf, bovine Lf pepsin hydrolysate, and the antimicrobial peptide
      "lactoferricin B" (Lfcin B). Other types of antifungal agents, amphotericin B,
      nystatin, and flucytosine did not show such combined effects with these Lf
      related compounds. The anti-Candida activity of bovine Lf or Lfcin B in
      combination with clotrimazole was shown to be synergistic by checkerboard
      analysis. Clinically isolated azole-resistant C. albicans strains were more
      susceptible to bovine Lf or Lfcin B than azole-susceptible strains. Trailing
      growth of an azole-resistant strain in the presence of fluconazole was reduced by
      the addition of sub-MIC levels of bovine Lf or Lfcin B. These results suggest
      that Lf-related compounds even at relatively low concentrations may function as
      an antifungal effector in combination with neutrophils thereby modulating azole
      antifungal efficacies in vivo.

PMID- 9781364
TI  - The mechanism of in vivo bacteriostasis of bovine lactoferrin.
AB  - Recently we have reported that orally administered bovine Lf(bLf) exerts
      bacteriostatic effects against bacterial overgrowth in the intestine of specific
      pathogen-free (SPF) mice fed milk. In this animal model, the in vivo
      bacteriostatic effect of bLf against the proliferation of intestinal
      Enterobacteriaceae, the bacteria most sensitive to bLf, was independent of the
      iron-chelating ability of bLf. In addition various proteolytic hydrolysates of
      bLf (with differing antibacterial activities in vitro) showed the same
      bacteriostatic effect as undigested bLf. These results suggest that the mechanism
      of in vivo bacteriostasis of Lf differs from the in vitro mechanism reported. In
      SPF mice fed milk differing in concentrations of lactose, glucose and galactose,
      the proliferation of intestinal Enterobacteriaceae was dependent on the
      carbohydrate concentration in the diet. The addition of 2% bLf to the diets
      significantly suppressed this carbohydrate-dependent proliferation of bacteria
      except in the case of diets containing excess carbohydrate. In germ-free mice fed
      sterile milk, the addition of 2% bLf to milk resulted in a significant decrease
      in concentrations of lactose, glucose and galactose in the cecal contents. In an
      in vitro assay system using everted sacs of the small intestine of SPF mice, both
      bLf and its pepsin hydrolysate apparently stimulated glucose absorption. Based on
      these findings, we propose that the in vivo mechanism of action of ingested bLf
      involves the stimulation of carbohydrate absorption resulting in a bacteriostatic
      effect against Enterobacteriaceae in the intestine of mice fed milk.

PMID- 9781365
TI  - The main systemic, highly effective, and quickly acting antimicrobial mechanisms
      generated by lactoferrin in mammals in vivo. Activity in health and disease.

PMID- 9781366
TI  - Regulation by lactoferrin of epidermal Langerhans cell migration.

PMID- 9781367
TI  - Lactoferrin stimulates the mitogen-activated protein kinase in the human
      lymphoblastic T Jurkat cell line.

PMID- 9781368
TI  - Effects of orally administered bovine lactoferrin on the immune system of healthy
      volunteers.
AB  - A protective effect of bovine lactoferrin (Lf) during lethal bacteraemia has been
      reported in mice. Also, protective effects of orally administered bovine Lf have
      been reported in cases of intractable stomatitis in cats and Cryptocaryon
      irritans infection in red sea bream. In this study, we examined the effects of
      orally administered bovine Lf on the immune system of healthy volunteers. Ten
      healthy male volunteers (age range of 31 to 55 years old) were given bovine Lf (2
      g/body/day) for 4 weeks. Blood samples were drawn before, during and after
      administration of Lf. Phagocytic activity and superoxide production activity of
      polymorphonuclear leukocytes (PMN) were evaluated from the number of PMN
      phagocytizing polymer particles and by the dichlorofluorescein (DCFH) oxidation
      assay, respectively. The expression levels of CD11b, CD16 and CD56 molecules on
      leukocytes were quantified using flow cytometry. The phagocytic activity of PMN
      increased during the period of Lf administration in 3 of the 10 volunteers. In 2
      of the 3 volunteers in which the phagocytic activity increased, PMN expressed
      CD16 at higher levels corresponding to the increase in 3 of the 10 volunteers,
      whereas the CD11b+ lymphocytes and CD56+ lymphocytes increased in 4 volunteers
      including the same 3 volunteers who showed an increase in CD16+. These results
      suggest that the proportion of natural killer (NK) cells among the lymphocytes
      might have increased in these subjects. It was demonstrated that the phagocytic
      activity or superoxide production activity of PMN or the proportions of CD11b+,
      CD16+ and CD56+ in lymphocytes was influenced by Lf administration in 7 of the 10
      volunteers, while the effects of Lf on the immune system differed in individual
      cases. These results suggest that Lf administration may influence primary
      activation of the host defense system.

PMID- 9781369
TI  - Lactoferrin and interleukin-6 interaction in amniotic infection.
AB  - Lactoferrin (Lf) has been found in most biological fluids including amniotic
      fluid and cervical mucoids in pregnant women, and released from neutrophils in
      response to the inflammation. As Lf possesses antimicrobial properties, it is
      widely considered to be an important component of the host defence against
      microbial infections. It is known that premature labor is caused by amniotic
      infection with the increase of prostaglandin production. High concentration of
      the inflammatory cytokines: interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6),
      tumor necrosis factor-alpha (TNF-alpha) in the amniotic fluid has been known.
      However, changes of Lf in amniotic fluid with infection has not been reported. In
      the present study, Lf concentrations in amniotic fluid were measured under the
      intra-uterine infections state and the biological significance of Lf was
      investigated. The effects of Lf on the IL-6 and IL-6mRNA production in cultured
      amnion cells were also investigated. The concentrations of Lf and IL-6 in
      amniotic fluid with CAM were 8.76 +/- 0.65 micrograms/ml and 6.92 +/- 4.88 ng/ml
      (n = 28) respectively and both were significantly higher (p < 0.01) than those
      without CAM [0.86 +/- 0.81 microgram/ml and 0.34 +/- 0.25 ng/ml (n = 31)].
      Significant positive correlation (r = 0.91, p < 0.01) between Lf and IL-6 levels
      in amniotic fluid was found. IL-6 production induced by lipopolysaccharide (LPS)
      (100 ng/ml) in cultured amnion cells was significantly inhibited (p < 0.05) under
      the physiological concentration of Lf in amnion. Total RNA was extracted from the
      amniotic cells by guianizine solution. RT-PCR procedure and product analysis were
      performed from one microgram aliquote of total RNA. beta-actin was used as an
      international standard and c-DNA samples were followed by 30 cycles of PCR. RT
      PCR product of IL-6 mRNA was detected by Southern hybridization. Expression of IL
      6 mRNA was inhibited by the addition of Lf. From the results, the possibility
      that Lf might suppress amniotic IL-6 production under the condition of amniotic
      infection is suggested. It is also suggested that Lf might act as self defence
      mechanism from intra-uterine infection.

PMID- 9781370
TI  - Inhibition of azoxymethane initiated colon tumor and aberrant crypt foci
      development by bovine lactoferrin administration in F344 rats.
AB  - The influence of bovine lactoferrin (bLf) on colon carcinogenesis was
      investigated in male F344 rats treated with azoxymethane (AOM). In experiment I,
      2% and 0.2% bLf, and Bifidobacterium longum (B. longum) as a positive control at
      3% were given in the diet for 4 weeks, along with two s.c. 15 mg/kg injections of
      AOM on days 1 and 8. The numbers of aberrant crypt foci (ACF) were decreased by
      both treatments. Similar results were obtained in experiment II of 13 weeks
      duration. In experiment III, animals were given three weekly injections of AOM
      and then received 2 or 0.2% bLf, 2% bLf-hydrolysate, or 0.1% bovine lactoferricin
      (bLfcin) for 36 weeks. No effects indicative of toxicity were noted, but
      significant reduction in both the incidence and number of adenocarcinomas of the
      large intestine was observed with almost all the treatments. Thus, the incidences
      of colon adenocarcinomas in the groups receiving 2 or 0.2% bLf, 2% bLf
      hydrolysate, or 0.1% bLfcin were 15%, 25%, 26.3% and only 10%, respectively, in
      contrast to the 57.5% control value (p < 0.01). ACF values also exhibited reduced
      development. Investigation of beta-glucuronidase revealed decrease in the cecal
      contents of animals receiving bLf. In addition, demonstration of enhancement of
      NK activity by bLf indicated that its inhibitory effects could have been related
      to elevated immune cytotoxicity.

PMID- 9781371
TI  - Bovine lactoferrin and Lactoferricin inhibit tumor metastasis in mice.
AB  - The effect of a bovine milk protein, lactoferrin (bLf), and a pepsin-generated
      peptide of bLf, lactoferricin (Lfcin-B), on inhibition of tumor metastasis
      produced by highly metastatic murine tumor cells, B16-BL6 melanoma and L5178Y
      ML25 lymphoma cells, was examined in experimental and spontaneous metastasis
      models using syngeneic mice. The subcutaneous (s.c.) administration of bovine apo
      lactoferrin (apo-bLf) and Lfcin-B 1 day after tumor inoculation significantly
      inhibited liver and spleen metastasis of L5178Y-ML25 cells and lung metastasis of
      B16-BL6 cells, whereas human apo-lactoferrin (apo-hLf) and bovine holo
      lactoferrin (holo-Lf) at the dose of 1 mg/mouse did not. Furthermore, both apo
      bLf and Lfcin-B, but not apo-hLf and holo-bLf, inhibited the number of tumor
      induced blood vessels and suppressed tumor growth on day 8 after tumor
      inoculations in an in vivo model. However, in a long-term analysis of tumor
      growth for up to 21 days after tumor inoculation, single administration of apo
      bLf significantly suppressed the growth of B16-BL6 cells throughout the
      examination period, but Lfcin-B showed inhibitory activity only during the early
      period (8 days). In spontaneous metastasis model, multiple administration of both
      apo-bLf and Lfcin-B significantly inhibited lung metastasis of B16-BL6 cells,
      however it was only apo-bLf that exhibited the inhibitory effect of tumor growth
      at the time of primary tumor amputation (on day 21) after tumor inoculation. The
      results suggest that apo-bLf and Lfcin-B inhibit tumor metastasis through
      different mechanisms, and that the inhibitory activity of bLf on tumor metastasis
      may be related to the property of iron (Fe3+)-saturation.

PMID- 9781373
TI  - A study of lactoferrin and antibodies against lactoferrin in neurological
      diseases.

PMID- 9781372
TI  - Lactoferrin is synthesized by mouse brain tissue and its expression is enhanced
      after MPTP treatment.
AB  - The biological role and origin of human lactoferrin (Lf) within the brain in
      normal and disease processes are as yet uncharted. In this context the origin and
      expression of brain Lf in normal and MPTP (1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine)-treated mice were investigated using immunohisto chemistry,
      PCR amplification and in situ hybridization. Lf immunostaining was observed both
      on sections of mouse lactating mammary gland, which was used as a positive
      control, and brains from young, adult and aged mice. Lf immunoreactivity was
      present in the pituitary gland, the hippocampus and the cortex of mouse brains
      and to a greater extent in older mice. After reverse transcription, Lf
      transcripts were also found in these brain sections. Lf distribution and
      expression in the MPTP-induced parkinsonian mouse model were next investigated. A
      marked depletion of dopamine and its metabolites: dihydroxyphenylacetic acid
      (DOPAC), homovanillic acid (HVA) and 5-hydroxy indole acetic acid (5-HIAA) occurs
      in the high dose MPTP-treated mice. The level of Lf expression was found to be
      greatly increased in the same animals but Lf immunoreactivity detected in the
      same brain region was not found increased in the affected areas.

PMID- 9781374
TI  - Antibodies to lactoferrin. A possible link between cow's milk intolerance and
      autoimmune disease.

PMID- 9781375
TI  - Prevalence and clinical significance of anti-lactoferrin autoantibodies in
      inflammatory bowel diseases and primary sclerosing cholangitis.
AB  - Anti-neutrophil cytoplasmic antibodies (ANCA) are autoantibodies directed against
      cytoplasmic constituents of neutrophil granulocytes. Antibodies with specificity
      for proteinase 3 and myeloperoxidase are seromarkers for systemic vasculitides.
      ANCA with specificity for lactoferrin were described in patients with several
      idiopathic inflammatory diseases, such as the inflammatory bowel diseases and
      rheumatoid arthritis. However, the clinical significance of anti-lactoferrin
      autoantibodies is still unclear. In this study, we determined the clinical
      significance of anti-lactoferrin autoantibodies in sera from large groups of
      patients with ulcerative colitis (UC), Crohn's disease (CD), and primary
      sclerosing cholangitis (PSC). Antibodies to human lactoferrin were detected by
      ELISA and by immunoblotting, using an extract of sonicated neutrophils as antigen
      source. Autoantibodies to lactoferrin were found in 29% of patients with UC, 13%
      of patients with CD, and 22% of patients with PSC. In inflammatory bowel
      diseases, the presence of anti-lactoferrin antibodies was not related to
      treatment, disease activity, duration of disease, or disease extent. In PSC, the
      presence of autoantibodies to lactoferrin did not correlate with duration of
      disease or the presence of cirrhosis. However, patients with PSC and coexistent
      UC had significantly more frequently antibodies to lactoferrin than PSC patients
      without IBD. In conclusion, autoantibodies to lactoferrin are a common feature of
      inflammatory bowel diseases and PSC. However, the clinical significance of those
      autoantibodies is limited as they lack sensitivity and specificity for those
      disorders. Future research should address the pathophysiological role of anti
      lactoferrin ANCA and the influence of anti-lactoferrin ANCA binding on the
      functional properties of the lactoferrin molecule.

PMID- 9781377
TI  - Lactoferrin. Its role in maturation and function of cells of the immune system
      and protection against shock in mice.

PMID- 9781376
TI  - Effect of lactoferrin on the phagocytic activity of polymorphonuclear leucocytes
      isolated from blood of patients with autoimmune diseases and Staphylococcus
      aureus allergy.
AB  - Phagocytic number (PN) and phagocytic index (PI) of neutrophils isolated from
      blood of patients with autoimmune diseases, allergy to Staphylococcus aureus and
      from blood of healthy individuals were examined. Our results concerning the
      influence of lactoferrin (Lf); (6.7 mg/l) on the PI of PMN showed that: 1) Lf
      enhances reliable PI of PMN at the 30-th minute starting the phagocytic reaction
      in patients with autoimmune disease in an active stage, in blood donors treated
      as healthy with the presence of autoantibodies, in patients with autoimmune
      diseases and proved autoantibodies against tissue, cell antigens and collagen, 2)
      Lf influences non-significantly PI of PMN in patients with autoimmune collagen
      diseases in remission, 3) Lf increases PI of PMN with 19% only in 58% from the
      assessed patients with Staphylococcus aureus, and 4) Lf decreases non
      significantly PI of PMN in the healthy controls. Our studies on the effect of Lf
      on the phagocytic activity of PMN suggest that Lf has stronger effect on the PN
      compared to the PI: 1) Lf enhances with 86% the PN in patients with
      Staphylococcus aureus, 2) Lf increases PN of PMN in all of the assessed patients
      with autoimmune collagen diseases in active stage (mean with 72%), and 3) Lf
      increases PN of PMN in 4 from the 5 investigated healthy controls (mean with
      22%). Our results show a "corrective" effect of Lf on the phagocytic functions in
      the investigated groups of patients. The possible mechanisms, by which Lf
      increases PN and PI of neutrophils, is discussed: 1) they may concern the
      antioxidative properties of Lf to block the iron ions in their catalytic inactive
      form or to take part as ferric-Lf in an oxidative-reduction processes on the
      plasma membrane and controlling transmembrane transport systems, 2) Lf decreases
      the negative surface charge and thus enhances the adherent ability of the PMN.
      Probably to this stimulated adherent ability dues the increased ingestion of
      bacteria in the presence of Lf, and 3) The "changed" membrane of PMN may have
      higher number receptors for Lf to bind more molecules of exogenous Lf. The
      increase of Lf binding which enhances the adherence and aggregation of
      neutrophils, facilitates the phagocytosis.

PMID- 9781378
TI  - Immunohistochemical demonstration of lactoferrin in human neoplastic tissues.

PMID- 9781379
TI  - Balancing needs, efficiency, and functionality in the provision of modeling
      software: a perspective of the NIH WinSAAM Project.
AB  - The development of new software or the refinement of existing software for new
      operating environments each calls for judicious balancing. On the one hand, we
      strive for simplicity, predictability, and operational protection as it is well
      recognized that software with these attributes will attract an audience of
      satisfied users. But, on the other hand, these attributes do not conjure a sense
      of power, efficiency, or flexibility, and these other properties are also
      appreciated by users, albeit a somewhat different group of users. The goal is to
      achieve a blend which isolates critical functionality, flexible control, and user
      support while meeting the needs of the broadest collection of serious users. In
      this chapter, we discuss the issues impacting the migration of SAAM to the
      Windows environment, the NIH WinSAAM Project, and we outline the steps taken to
      ensure its feasibility. In addition, we describe a new paradigm for software
      development and use which ensures the durability of the software for modeling.

PMID- 9781380
TI  - Compartmental modeling of human lactation.
AB  - A difficult task for a novice modeler is beginning a modeling project. The
      methods described here delineate the modeling process step by step. Aristole is
      quoted as having said "One learns to play the flute by playing the flute," and
      the same principle holds somewhat for modeling. An excellent means for
      understanding modeling is to work with example models, altering rate coefficients
      and model structure, to learn first-hand the mechanics of the process. An
      excellent resource for viewing and downloading published models is the Library of
      Mathematical Models of Biological Systems, and can be accessed via the World Wide
      Web at the address http://gopher.dml.georgetown.edu/model/model.html++ + . This
      modeling library provides access to working models of biological systems.
      Experimenting with available examples of models, such as those presented in this
      volume and those available through the Modeling Library, provides an excellent
      opportunity for new modelers to get started in compartmental modeling.

PMID- 9781381
TI  - Modeling protein turnover: a module for teaching modeling.

PMID- 9781382
TI  - Developing and testing integrated multicompartment models to describe a single
      input multiple-output study using the SAAM II software system.
AB  - As measurement devices become more sophisticated, it is possible to design more
      complex input-output studies, i.e., studies where data are obtained from several
      sites in the system under study. To interpret the resulting data requires models
      which can integrate known information about the system under study while
      simultaneously describing the data. In this chapter, we will illustrate how to
      develop and test a model structure for a single-input multiple-output study using
      the SAAM II software system. This system has been designed to make the use of
      sound modeling principles easy. It will be assumed that a known amount of a
      radiolabeled substance was injected as a bolus into plasma, that this substance
      can bind to and be taken up by red cells, that its only route of elimination is
      through the urine, and that external measurements are possible over a target
      organ. The steps in developing a model structure will make use of SAAM II's
      forcing function capability to show how the system can be decoupled; this will
      permit us to postulate model structures for the various subsystems accessible to
      measurement. We will then show how to use this information to postulate a model
      describing all the data, and how to test this model structure. This will permit
      us to comment on those parts of the system not accessible for experimental
      measurement. We will end with a general discussion of how to test for goodness-of
      fit and model order.

PMID- 9781383
TI  - Compartmental models: theory and practice using the SAAM II software system.
AB  - Understanding in vivo the functioning of metabolic systems at the whole-body or
      regional level requires one to make some assumptions on how the system works and
      to describe them mathematically, that is, to postulate a model of the system.
      Models of systems can have different characteristics depending on the properties
      of the system and the database available for their study; they can be
      deterministic or stochastic, dynamic or static, with lumped or distributed
      parameters. Metabolic systems are dynamic systems and we focus here on the most
      widely used class of dynamic (differential equation) models: compartmental
      models. This is a class of models for which the governing law is conservation of
      mass. It is a very attractive class to users because it formalizes physical
      intuition in a simple and reasonable way. Compartmental models are lumped
      parameter models, in that the events in the system are described by a finite
      number of changing variables, and are thus described by ordinary differential
      equations. While stochastic compartment models can also be defined, we discuss
      here the deterministic versions--those that can work with exact relationships
      between model variables. These are the models most widely used in discussions of
      endocrinology and metabolism. In this chapter, we will discuss the theory of
      compartmental models, and then discuss how the SAAM II software system, a system
      designed specifically to aid in the development and testing of multicompartmental
      models, can be used.

PMID- 9781384
TI  - Approaches to population kinetic analysis with application to metabolic studies.
AB  - Population kinetic analysis is the methodology traditionally used to quantify
      inter-subject variability in pharmacokinetic studies. In the statistics
      literature, it is also called analysis of repeated measurement data or analysis
      of longitudinal data. In this work, we will state the population kinetics problem
      and give some historical background to its significance. Then we will describe
      and apply to case studies in intermediary metabolism various two-stage and other
      parametric methods for nonlinear mixed effects models. We will then briefly
      review the software available for population kinetic analysis.

PMID- 9781385
TI  - The mathematics behind modeling.
AB  - The purpose of this chapter has been to furnish insight into the theoretical
      background on which compartmental modeling software packages are based. To
      accomplish this goal, only the basic ideas were stressed, avoiding discussion of
      the intricacies required for efficiency. The object was to remove the mystery
      from these powerful programs by examining the fundamental ideas which make them
      tick. The first section was concerned with how compartmental models are built up
      and how to obtain information concerning the system behavior described by these
      models. The cornerstone here is to describe a system by determining how it
      behaves over (typically) very short time periods. This leads to a differential
      equation description of a compartmental system. Information can be extracted from
      these equations by returning to their basic meaning, illustrated in their
      derivation. Computers are ideal for obtaining this information by piecing
      together the results obtained over short time periods, to find the behavior over
      long time periods. In an actual situation governed by a compartmental model, it's
      often the case that we may know only the form of the model, but not the values of
      the rate constants which must be known for its effective use. The second section
      of the chapter was devoted to the practical problem of determining the rate
      constants of the model, based on observed data. This is a matter of searching for
      those values which, in some sense, best fit the data. To attack this problem we
      need a reasonable criterion to judge how well a proposed model fits the data. We
      chose to use the total squared deviation, psi, which is the most common such
      criterion--but not the only reasonable one. The search technique we examined-
      steepest descent--is based on a simple idea: looking at the total squared
      deviation criterion geometrically. In graphical terms, the best fit corresponds
      to finding the low point on a surface, whose height above any point at sea level
      is computable. If we could imagine the view of someone trying to find the low
      point from some arbitrarily chosen initial position on this mountain-like
      surface, we would look around and find the direction where (close by) the
      mountain drops off most steeply. We would go in that specific direction until we
      reach a low point, moving only along this initially chosen direction. At this new
      low point, we could change again to a direction of steepest descent, and keep
      repeating this process until we make no further effective downward progress. No
      guarantee in general is made for this process, but it often works. Finally,
      having found the best values for the rate constants, we must recognize that if
      the data is affected by factors not explicitly taken into account in the model,
      the variability induced by these factors precludes a perfect fit. For this
      reason, it is finally necessary to determine how good the model is, as a
      description of the data, and how accurate are the fitted rate constants. For the
      model fit, the sample RMS error (simply related to the total squared deviation,
      and often the same as the sample standard deviation) may be used. For determining
      the accuracy of the fitted rate constants, practical methods based on computer
      software simulations are recommended.

PMID- 9781386
TI  - Distributing working versions of published mathematical models for biological
      systems via the Internet.
AB  - Mathematical models are useful tools for investigating complex systems. By
      representing physiological systems as models, theories can be tested
      quantitatively against data from the system. Models can be used to explore new
      theories prior to experimentation and to design studies to optimize experimental
      resources. They can also be used as teaching tools to illustrate physiochemical
      principles. In spite of their usefulness and the time invested in developing
      models, published models are often underused due to the difficulty in obtaining
      working versions of the model. To address this problem we have designed a library
      for mathematical models of biological systems on the Internet. The library
      contains published models of biological systems in formats compatible with
      several modeling packages, from the fields of physiology, metabolism,
      endocrinology, biochemistry, and chemistry. The models can be viewed graphically,
      model solutions can be viewed as plots against data, and models can be downloaded
      to be run with software on the user's own system. The address of the library is:
      http://biomodel.georgetown.edu/model/ Investigators are invited to submit working
      versions of published models to the library. Models can be submitted
      electronically at the time a manuscript is accepted for publication. As journals
      go online, articles containing models can be linked to working versions of the
      models in the library. By increasing access to working versions of models, more
      of the investment in kinetic studies and model development can be realized.

PMID- 9781387
TI  - Measurement error and dietary intake.
AB  - This chapter reviews work of Carroll, Freedman, Kipnis, and Li (1998) on the
      statistical analysis of the relationship between dietary intake and health
      outcomes. In the area of nutritional epidemiology, there is some evidence from
      biomarker studies that the usual statistical model for dietary measurements may
      break down due to two causes: (a) systematic biases depending on a person's body
      mass index; and (b) an additional random component of bias, so that the error
      structure is the same as a one-way random effects model. We investigate this
      problem, in the context of (1) the estimation of the distribution of usual
      nutrient intake; (2) estimating the correlation between a nutrient instrument and
      usual nutrient intake; and (3) estimating the true relative risk from an
      estimated relative risk using the error-prone covariate. While systematic bias
      due to body mass index appears to have little effect, the additional random
      effect in the variance structure is shown to have a potentially important impact
      on overall results, both on corrections for relative risk estimates and in
      estimating the distribution usual of nutrient intake. Our results point to a need
      for new experiments aimed at estimation of a crucial parameter.

PMID- 9781388
TI  - Statistical models for quantitative bioassay.
AB  - We discuss various statistical approaches useful in the analysis of nutritional
      dose-response data with a continuous response. The emphasis is on the
      multivariate case with several predictors. The methods which will be discussed
      can be classified into parametric models, including change-point models, and
      nonparametric models, which rely on smoothing methods such as weighted local
      linear fitting. The methods will be illustrated with the analysis of data
      generated from a folate depletion-repletion bioassay experiment conducted on
      rats, where the measured growth rate of the rate is the response variable. We
      also discuss the biological conclusions that can be drawn from applying various
      statistical methods to this data set.

PMID- 9781389
TI  - Statistical issues in assay development and use.

PMID- 9781390
TI  - Statistical tools for the analysis of nutrition effects on the survival of
      cohorts.
AB  - We discuss various methods which can be employed for the comparative analysis of
      samples of response curves. In the application discussed here, these curves are
      hazard functions, each generated by the survival data obtained for a cohort of
      experimental subjects which are fed a specific diet. It is demonstrated how
      comparisons of the effects of different diets on survival can be carried out by
      employing statistical techniques for inference on samples of curves. The methods
      are illustrated with data on the survival of large cohorts of male and female
      Mediterranean fruit flies under full diet and under protein deprivation. These
      statistical methods allow one to investigate differences between the samples of
      hazard functions generated by the four groups defined by combinations of sex and
      diet.

PMID- 9781391
TI  - Development of a compartmental model describing the dynamics of vitamin A
      metabolism in men.
AB  - Model-based compartmental analysis was used with the Simulation, Analysis and
      Modeling (SAAM) computer programs to analyze data on plasma retinoid kinetics in
      adult male subjects for 7 d after a single oral dose of 105 mumol of [8,9,19
      13C]retinyl palmitate. We present here the data for one subject and discuss in
      detail the steps taken to develop a physiologically-based compartmental model
      that describes the dynamic behavior of plasma retinyl esters, [12C]retinol,
      [8,9,19-13C]retinol, and the sum of [12C] and [13C]retinol. First an absorption
      model was developed to fit data on the plasma appearance and disappearance of
      retinyl esters; this was used as input in development of models for labeled and
      unlabeled retinol. The large oral load of labeled vitamin A perturbed the
      unlabeled tracee system, and thus parallel models for tracer and tracee were
      developed; and a time-variant fractional transfer coefficient was incorporated
      into the tracee model. Following the absorption model, four-compartment models
      were developed to describe the dynamics of both labeled and unlabeled retinol.
      These models predict that, in spite of the large vitamin A load, the absorption
      efficiency was 34%; hepatic (presumably parenchymal cell) processing of the
      absorbed dose was essentially complete by 24 h; and, by 7 days, approximately 80%
      of the absorbed dose was in a compartment that presumably represents stored liver
      retinyl esters. The model also predicts that approximately 50 mumol of retinol
      passed through the plasma each day, compared to an estimated utilization rate of
      4 mumol/day. This project provides unique and important information about whole
      body vitamin A dynamic in humans, and presents approaches to specific modeling
      issues that may be encountered by others.

PMID- 9781392
TI  - Compartmental models of vitamin A and beta-carotene metabolism in women.
AB  - We have developed compartmental models of vitamin A and beta-carotene (beta C)
      metabolism in women living under controlled conditions on diets with known
      concentrations of vitamins and carotenoids. Fourteen healthy adult women were
      given either retinyl-d4 acetate, or beta C-d8 before breakfast. Natural and
      stable-isotopes of retinol and beta C were collected in serum for up to 95 days
      or 20 days, respectively. Stable isotopes were separated from other components
      and measured by GC-MS or HPLC-UV. Preformed retinyl-d4 acetate metabolism in all
      women tested can be accurately described by a simple four-compartment model.
      However, the model did not fit one women initially, when she had marginal vitamin
      A status. We tested the hypothesis that dietary changes of beta C intake have
      important roles on the kinetics of vitamin A metabolism. Dietary changes of beta
      C intake did not influence the turnover rate of retinol in any compartment.
      However, it did result in changes in steady-state masses and residence times of
      retinol in several compartments. A working compartmental model for beta C
      metabolism was developed. The kinetics of retinol-d4 formed from beta C is more
      complicated than the pre-formed retinol-d4. Results suggest that beta C-d8
      readily converts into retinol-d4 with high inter-individual variability.

PMID- 9781393
TI  - The dynamics of folic acid metabolism in an adult given a small tracer dose of
      14C-folic acid.
AB  - Folate is an essential nutrient that is involved in many metabolic pathways,
      including amino acid interconversions and nucleotide (DNA) synthesis. In
      genetically susceptible individuals and populations, dysfunction of folate
      metabolism is associated with severe illness. Despite the importance of folate,
      major gaps exist in our quantitative understanding of folate metabolism in
      humans. The gaps exist because folate metabolism is complex, a suitable animal
      model that mimics human folate metabolism has not been identified, and suitable
      experimental protocols for in vivo studies in humans are not developed. In
      general, previous studies of folate metabolism have used large doses of high
      specific activity tritium and 14C-labeled folates in clinical patients. While
      stable isotopes such as deuterium and 13C-labeled folate are viewed as ethical
      alternatives to radiolabeled folates for studying metabolism, the lack of
      sensitive mass spectrometry methods to quantify them has impeded advancement of
      the field using this approach. In this chapter, we describe a new approach that
      uses a major analytical breakthrough, Accelerator Mass Spectrometry (AMS).
      Because AMS can detect attomole concentrations of 14C, small radioactive dosages
      (nCi) can be safely administered to humans and traced over long periods of time.
      The needed dosages are sufficiently small that the total radiation exposure is
      only a fraction of the natural annual background radiation of Americans, and the
      generated laboratory waste may legally be classified non-radioactive in many
      cases. The availability of AMS has permitted the longest (202 d) and most
      detailed study to date of folate metabolism in a healthy adult human volunteer.
      Here we demonstrate the feasibility of our approach and illustrate its potential
      by determining empirical kinetic values of folate metabolism. Our data indicate
      that the mean sojourn time for folate is in the range of 93 to 120 d. It took >
      or = 350 d for the absorbed portion of small bolus dose of 14C-folic acid to be
      eliminated completely from the body.

PMID- 9781394
TI  - Human zinc metabolism: advances in the modeling of stable isotope data.
AB  - Compartmental modeling is a useful tool for investigating metabolic systems and
      processes. We and others have applied it to the study of zinc metabolism in
      humans. Because existing models could not be accurately fitted to our data, we
      have developed a new model of human zinc metabolism based on stable isotope
      tracer data from studies of five healthy adults. Multiple isotope tracers were
      administered orally and intravenously and the resulting enrichment measurement in
      plasma, erythrocytes, urine, and feces. These tracer kinetic data, along with
      other measured and calculated tracee and steady-state data, were used to develop
      the model. A single model structure composed of fourteen compartments was found
      to be suitable for all subjects. Model development and fitting of data and model
      for each subject were accomplished using the SAAM/CONSAM computer programs. The
      model development and fiting processes are described and exemplified using data
      from one of the subjects. While identifiability could not be demonstrated a
      priori due to the model's complexity, parameter statistics for the fitted models
      did show most parameters to be adequately identified a posteriori.

PMID- 9781395
TI  - Key features of copper versus molybdenum metabolism models in humans.

PMID- 9781397
TI  - Modeling of energy expenditure and resting metabolic rate during weight loss in
      humans.

PMID- 9781396
TI  - Insights into bone metabolism from calcium kinetic studies in children.
AB  - Changes in the mineralization rate of the skeleton during childhood are related
      to normal growth and pubertal development. These may be affected by genetic
      factors, including race and gender, and by the presence of abnormalities of
      growth or hormonal abnormalities such as occur in children with chronic
      illnesses. We have used multicompartmental studies to examine calcium kinetics in
      healthy children ranging in age from premature infants of 1-2 kg body weight
      through adolescence. These studies are performed using orally and intravenously
      administered stable isotopes of calcium. Sample collection requires multiple
      blood samples to be obtained during the initial time period after isotope dosing,
      which is feasible in older children using an indwelling catheter. We have found
      that the peak rate for both bone calcium deposition and removal occurs in girls
      during the year before menarche. Peak kinetic rates decrease in an exponential
      fashion post-menarche. On a body-weight basis, the greatest rates of bone calcium
      deposition and removal are in infants, especially premature infants.

PMID- 9781399
TI  - Modeling ruminant digestion and metabolism.

PMID- 9781398
TI  - Development and application of a compartmental model of 3-methylhistidine
      metabolism in humans and domestic animals.
AB  - Measurement of urinary 3-methylhistidine (3MH) excretion is the primary in vivo
      method to measure skeletal muscle (myofibrillar) protein breakdown. This method
      requires quantitative collection of urine and is based on the assumption that no
      metabolism of 3MH occurs once it is released from actin and myosin. This is true
      in most species, but in sheep and swine a proportion is retained in muscle as a
      dipeptide, balenine. In neither of these species does urine 3MH yield any data on
      the metabolism of 3MH. We have conducted studies that propose that 3MH metabolism
      in humans, cattle, dogs, swine, and sheep can be defined from a single bolus
      infusion of a stable isotope 3-[methyl-2H3]-methylhistidine. Following the bolus
      dose of the stable isotope tracer, serial blood samples and/or urine was
      collected over three to five days. A minimum of three exponentials were required
      to describe the plasma decay curve adequately. The kinetic linear-time-invariant
      models of 3MH metabolism in the whole animal were constructed by using the
      SAAM/CONSAM modeling program. Three different configurations of a three
      compartment model are described: (A) A simple three-compartment model for humans,
      cattle, and dogs, in which plasma kinetics (3-[methyl-2H3]-MH/3MH) are described
      by compartment 1 and with one urinary exit from compartment 1. (B) A plasma
      urinary kinetic three-compartment model with two exits was used for sheep with a
      urinary exit out of compartment 1 and a balenine exit out of a tissue compartment
      3. (C) A plasma three-compartment model was used in swine with an exit out of a
      tissue compartment 3. The kinetic parameters reflect the differences in known
      physiology of humans, cattle, and dogs as compared to sheep and swine that do not
      quantitatively excrete 3MH into the urine. Steady-state model calculations define
      masses and fluxes of 3MH between three compartments and, importantly, the de novo
      production of 3MH. The de novo production of 3MH for humans, cattle, dogs, sheep,
      and swine are 3.1, 6.0, 12.1, 10.3, and 7.2 mumol x kg-1 x d-1, respectively. The
      de novo production of 3MH as calculated by the compartmental model was not
      different when compared to 3MH production as calculated via traditional urinary
      collection. Additionally, data suggest that steady-state compartment masses and
      mass transfer rates may be related to fat free mass and muscle mass in humans and
      swine, respectively. In conclusion, models of 3MH metabolism have been developed
      in numerous species, and these models can be used for the assessment of muscle
      proteolysis and 3MH kinetics without the collection of urine. This methodology is
      less evasive and will be useful in testing further experimental designs that
      alter myofibrillar protein breakdown.

PMID- 9781400
TI  - Designing a radioisotope experiment using a dynamic, mechanistic model of protein
      turnover.

PMID- 9781401
TI  - Protocol development for biological tracer studies.
AB  - Improved instrumentation and the increased availability of labeled compounds have
      democratized the application of isotope-dilution (tracer) methodology in nutrient
      metabolism. Still, the most challenging aspects of tracer experimentation reside
      in the steps that precede the measurement of an isotopically labeled tracer, i.e.
      the design of a suitably labeled tracer and its isolation and purification from
      complex biological matrices. Construction of useful mathematical models of
      nutrient dynamics require methodologies that guarantee that the integrity of the
      tracer is maintained across the entire sampling and analyte isolation protocol.
      The ability to provide accurate and reliable data highlights a need for
      analytical chemists to play a central role in these studies. In this regard,
      examples and discussion of issues relevant to stable-isotope experimentation are
      provided.

PMID- 9781402
TI  - Plasma source mass spectrometry in experimental nutrition.
AB  - The development and commercial availability of plasma ion source, specifically
      inductively coupled plasma, mass spectrometers (ICP-MS) have significantly
      extended the potential application of stable isotopes for nutritional modeling.
      The status of research and commercial ICP-MS instruments, and their applications
      and limitations for stable isotopic studies are reviewed. The consequences of
      mass spectroscopic resolution and measurement sensitivity obtainable with
      quadrupole, sector, time-of-flight, and trap instruments on stable isotope
      analysis are examined. Requirements for reliable isotope measurements with
      practical biological samples including tissues and fluids are considered. The
      possibility for stable isotope analysis in chemically separated compounds
      (speciation) also is explored. On-line compound separations by chromatography or
      electrophoresis, for example, have been combined instrumentally with ICP-MS. Som
      possibilities and requirements are described for stable isotope speciation
      analysis.

PMID- 9781403
TI  - Accelerator mass spectrometry as a bioanalytical tool for nutritional research.
AB  - Accelerator Mass Spectrometry is a mass spectrometric method of detecting long
      lived radioisotopes without regard to their decay products or half-life. The
      technique is normally applied to geochronology, but is also available for
      bioanalytical tracing. AMS detects isotope concentrations to parts per
      quadrillion, quantifying labeled biochemicals to attomole levels in milligram
      sized samples. Its advantages over non-isotopic and stable isotope labeling
      methods are reviewed and examples of analytical integrity, sensitivity,
      specificity, and applicability are provided.

PMID- 9781404
TI  - Stereotype efficiency reconsidered: encoding flexibility under cognitive load?
AB  - According to the encoding flexibility model, stereotypes are efficient because
      they facilitate, in different ways, the encoding of both stereotype-consistent
      and stereotype-inconsistent information when capacity is low. Because
      stereotypical information is conceptually fluent, it may be easily understood,
      even when resources are scant. As a result, processing resources may shift from
      stereotypical toward counterstereotypical information, which is difficult to
      comprehend under such conditions. Thus, whereas inconsistent information receives
      greater attention (Experiments 1-3) and perceptual encoding (Experiment 4) when
      resources are depleted, the conceptual meaning of consistent information is
      extracted to a greater degree under such conditions (Experiment 5). Potential
      moderating roles of stereotype strength and perceiver motivations are discussed,
      as are the implications of these results for dual process models of stereotyping.

PMID- 9781405
TI  - Immune neglect: a source of durability bias in affective forecasting.
AB  - People are generally unaware of the operation of the system of cognitive
      mechanisms that ameliorate their experience of negative affect (the psychological
      immune system), and thus they tend to overestimate the duration of their
      affective reactions to negative events. This tendency was demonstrated in 6
      studies in which participants overestimated the duration of their affective
      reactions to the dissolution of a romantic relationship, the failure to achieve
      tenure, an electoral defeat, negative personality feedback, an account of a
      child's death, and rejection by a prospective employer. Participants failed to
      distinguish between situations in which their psychological immune systems would
      and would not be likely to operate and mistakenly predicted overly and equally
      enduring affective reactions in both instances. The present experiments suggest
      that people neglect the psychological immune system when making affective
      forecasts.

PMID- 9781406
TI  - Everyday stressors and gender differences in daily distress.
AB  - This article examines gender differences in psychological distress by assessing
      men's and women's experience of daily stressors and psychological distress in a
      sample of 166 married couples. Respondents completed a structured daily diary
      each day over the course of 42 days. Results showed that women reported a higher
      prevalence of high distress days and a lower prevalence of distress-free days
      than men. Gender differences in daily distress were attributable largely to women
      experiencing more onsets of distress episodes rather than being more likely to
      continue in a distress state from one day to subsequent days. Results from
      hierarchical linear models (HLM) indicated that the significant gender
      differences diminished after respondents' daily stressors were taken into
      account. Implications of these findings for gender role and rumination theories
      are discussed.

PMID- 9781407
TI  - Long-term outcome maximization and the reduction of interindividual-intergroup
      discontinuity.
AB  - Two experiments demonstrated that different procedures can be used to reduce the
      tendency for intergroup relations to be more competitive than interindividual
      relations. Experiment 1 revealed that this tendency was reduced when individual
      or group participants interacted with individual or group confederates who
      followed a tit-for-tat strategy as opposed to a Pavlov strategy or a standard
      control condition that did not involve confederates. Experiment 2 revealed that
      the tendency for groups to be more competitive than individuals was less
      pronounced with successive responding than with simultaneous responding. Further
      results indicated that the higher the total session score on the Consideration of
      Future Consequences Scale, the less the competition between groups. The results
      from both experiments were interpreted as indicating that intergroup
      competitiveness can be reduced by inducing a concern with long-term outcomes.

PMID- 9781408
TI  - Looking back at anger: reference periods change the interpretation of emotion
      frequency questions.
AB  - When asked to report on behaviors and experiences, participants draw on the
      specified reference period to infer the question meaning: Short reference periods
      suggest that the question pertains to frequent experiences; long reference
      periods suggest that it pertains to rare ones. Because frequent experiences are
      typically less intense than rare ones, this meaning shift results in reports of
      different experiences. Three experiments support this analysis in the domain of
      emotion reports. Participants asked how frequently they get angry (a) assumed
      that the question refers to less intense and more frequent episodes when
      presented with a short (1-week) rather than a long (1-year) reference period, (b)
      reported more extreme episodes in the latter case, and (c) provided differential
      frequency reports. These differences reflect conversational inference processes
      and cannot be fully accounted for by memory search biases.

PMID- 9781410
TI  - Prosocial self-schemas, self-awareness, and children's prosocial behavior.
AB  - Three studies examined the hypothesis that a child's prosocial self-schema
      predicts prosocial behavior. In Study 1, only self-aware boys showed a self
      schema-behavior relation. Study 2 altered both salience of donating opportunity
      and relationship of recipient to donor. The hypothesized Self-Awareness x Self
      Schema interaction was significant, and there were no gender differences. Study 3
      systematically manipulated the salience of the donating opportunity. All
      participants were self-aware. For boys in high and low salience conditions,
      prosocial self-schema predicted donating behavior. For girls, prosocial self
      schema predicted behavior only in the high salience condition. The findings
      demonstrate that self-schemas can regulate behavior when participants are self
      aware. Girls, however, may require higher salience of the donating opportunity
      for the self-schema to affect their behavior.

PMID- 9781409
TI  - Los Cinco Grandes across cultures and ethnic groups: multitrait multimethod
      analyses of the Big Five in Spanish and English.
AB  - Spanish-language measures of the Big Five personality dimensions are needed for
      research on Hispanic minority populations. Three studies were conducted to
      evaluate a Spanish version of the Big Five Inventory (BFI) (O. P. John et al.,
      1991) and explore the generalizability of the Big Five factor structure in Latin
      cultural groups. In Study 1, a cross-cultural design was used to compare the
      Spanish and English BFI in college students from Spain and the United States, to
      assess factor congruence across languages, and to test convergence with
      indigenous Spanish Big Five markers. In Study 2, a bilingual design was used to
      compare the Spanish and English BFI in a college-educated sample of bilingual
      Hispanics and to test convergent and discriminant validity across the two
      languages as well as with the NEO Five Factor Inventory in both English and
      Spanish. Study 3 replicated the BFI findings from Study 2 in a working-class
      Hispanic bilingual sample. Results show that (a) the Spanish BFI may serve as an
      efficient, reliable, and factorially valid measure of the Big Five for research
      on Spanish-speaking individuals and (b) there is little evidence for substantial
      cultural differences in personality structure at the broad level of abstraction
      represented by the Big Five dimensions.

PMID- 9781411
TI  - Implicit and self-attributed dependency strivings: differential relationships to
      laboratory and field measures of help seeking.
AB  - D. C. McClelland, R. Koestner, and J. Weinberger (1989) argued that self-report
      tests assess self-attributed needs (i.e., motives that are openly acknowledged by
      the actor), whereas projective tests assess implicit needs (i.e., motives that
      affect behavior without conscious awareness on the actor's part). The present
      studies examined the effects of implicit and self-attributed dependency strivings
      on laboratory and field measures of help seeking. In Study 1, college students
      were prescreened with widely used objective and projective dependency tests, then
      underwent an information manipulation designed to influence their attention to
      dependency-related issues. As expected, dependency status and information
      condition interacted to predict help-seeking behavior. Study 2 used experience
      sampling procedures to demonstrate that implicit and self-attributed dependency
      needs differentially predict direct and indirect help seeking in vivo.

PMID- 9781412
TI  - Protective factors in adolescent health behavior.
AB  - The role of psychosocial protective factors in adolescent health-enhancing
      behaviors--healthy diet, regular exercise, adequate sleep, good dental hygiene,
      and seatbelt use--was investigated among 1,493 Hispanic, White, and Black high
      school students in a large, urban school district. Both proximal (health-related)
      and distal (conventionality-related) protective factors have significant positive
      relations with health-enhancing behavior and with the development of health
      enhancing behavior. In addition, in cross-sectional analyses, protection was
      shown to moderate risk. Key proximal protective factors are value on health,
      perceived effects of health-compromising behavior, and parents who model health
      behavior. Key distal protective factors are positive orientation to school,
      friends who model conventional behavior, involvement in prosocial activities, and
      church attendance. The findings suggest the importance of individual differences
      on a dimension of conventionality-unconventionality. Strengthening both proximal
      and distal protective factors may help to promote healthful behaviors in
      adolescence.

PMID- 9781413
TI  - Social comparison preferences among cancer patients as related to neuroticism and
      social comparison orientation.
AB  - Effects of neuroticism and social comparison orientation on social comparison
      among cancer patients were examined. A computer program that enabled patients to
      access information about fellow patients' disease-related experiences was
      developed. Patients selected more interviews concerning more as compared to less
      fortunate others, spent more time reading, and showed more favorable reactions to
      such information. Individuals with a strong comparison orientation in particular
      tended to engage in and to respond to social comparison. Neuroticism was
      associated with higher interest in social comparison and with less favorable
      reactions, regardless of its direction. High-neurotic individuals reacted more
      positively to upward than to downward comparisons, whereas the reactions of low
      neurotic individuals were unaffected by comparison direction. The latter effect
      was replicated using a general affect measure, but solely among individuals with
      a strong comparison orientation.

PMID- 9781414
TI  - Synergistic approaches based on nonchromatographic continuous separation
      techniques (solid-phase extraction and pervaporation) and chromatography
      couplings.
AB  - Approaches based on continuous separation units coupled to either liquid or gas
      chromatography for improving the features of analytical methods are proposed.
      Examples of solid-phase separation-liquid chromatography for the determination of
      fat-soluble vitamins and their metabolites in clinical samples, and pervaporation
      gas chromatography for the determination of volatile compounds in solid
      environmental samples are described. The clean-up and preconcentration effect
      achieved by the former coupling and the easy and effective solid-sample
      pretreatment in the latter clearly show their utility. The use of pervaporation
      as an advantageous alternative to headspace is demonstrated.

PMID- 9781415
TI  - Analysis of amikacin by liquid chromatography with pulsed electrochemical
      detection.
AB  - The analysis of amikacin by liquid chromatography using a column packed with
      poly(styrene-divinylbenzene) and pulsed electrochemical detection on a gold
      electrode is described. A two-step gradient was necessary to obtain a good
      separation together with a reasonable analysis time of 60 min. The mobile phases
      consisted of an aqueous solution of 1 g/l or 60 g/l sodium sulfate, 1.8 g/l
      sodium octanesulfonate and 50 ml/l 0.2 M phosphate buffer, pH 3.0. Sodium
      hydroxide was added postcolumn. The influence of the different chromatographic
      parameters on the separation was investigated. When a number of commercial
      samples of amikacin was analyzed using this method, ten different components were
      separated.

PMID- 9781416
TI  - Confirmation of residues of thyreostatic drugs in thyroid glands by multiple mass
      spectrometry after thin-layer chromatographic screening.
AB  - A method is described for the confirmation of high-performance thin layer
      chromatography (HPTLC) suspect results of residues of thyreostatic drugs in
      thyroid tissue. The method is based on the infusion of the remainder of the
      extract used for HPTLC via the electrospray interface into a mass spectrometer
      operating in the multiple stage mass spectrometry (MSn) mode. The clean-up of the
      samples was performed with a selective extraction procedure, based on a specific
      complex formation of the drugs with mercury ions, bound in an affinity column.
      The thyreostatic drugs were derivatised with 7-chloro-4-nitrobenzo-2-oxa-1,3
      diazole.

PMID- 9781418
TI  - Simultaneous determination of methylphenobarbital enantiomers and phenobarbital
      in human plasma by on-line coupling of an achiral precolumn to a chiral liquid
      chromatographic column.
AB  - A fully automated liquid chromatographic (LC) method for the simultaneous
      determination of methylphenobarbital enantiomers and phenobarbital in human
      plasma has been developed. The method is based on the use of a precolumn packed
      with an internal-surface reversed-phase packing material (LiChrospher ADS) for
      sample clean-up coupled to LC analysis on a cellulose tris(4-methylbenzoate)
      based chiral stationary phase (Chiralcel OJ-R). A 100-microliter plasma sample
      was injected directly on the precolumn packed with LiChrospher RP-18 ADS using a
      mixture of pH 5.0 phosphate buffer-methanol (97:3, v/v) as washing liquid. The
      analytes were then eluted in the back-flush mode with the LC mobile phase. The
      enantiomeric separation of methylphenobarbital was achieved on Chiralcel OJ-R).
      The retention times were modelled using a D-optimal design with ten experimental
      points in order to optimise the LC mobile phase for the separation of
      phenobarbital from the enantiomers of mephobarbital. The factors selected were
      the acetonitrile content, the pH and the sodium perchlorate concentration in the
      mobile phase. A Derringer's desirability function was used to find an optimal and
      robust solution within the experimental domain. The mobile phase selected
      consisted of a mixture of pH 7.0 phosphate buffer-acetonitrile (60:40, v/v). The
      elution profiles of phenobarbital, methylphenobarbital and blank plasma samples
      on the precolumn and the time needed for analyte transfer from the precolumn to
      the analytical column were then determined. Finally, the method developed was
      validated.

PMID- 9781417
TI  - Determination of molsidomine and its active metabolite in human plasma using
      liquid chromatography with tandem mass spectrometric detection.
AB  - Pharmacokinetic studies of molsidomine require a sensitive analytical method to
      allow the determination of concentrations of this compound and its active
      metabolite 3-morpholinosydnonimine (Sin-1) in the ng/ml range in plasma. The
      method developed is based on on-line LC-MS-MS using pneumatically assisted
      electrospray ionisation as an interface, preceded by off-line solid-phase
      extraction (SPE) on disposable extraction cartridges (DECs). The SPE operations
      were performed automatically by means of a sample processor equipped with a
      robotic arm (automated sample preparation with extraction cartridges; ASPEC
      system). The DEC, filled with phenyl-modified silica, was first conditioned with
      methanol and water. The washing step was performed with water. Finally, the
      analytes were successively eluted with methanol containing formic acid (0.2%) and
      water. The liquid chromatographic separation of molsidomine and Sin-1 was
      achieved on an RP-8 stationary phase (5 microns). The mobile phase was a mixture
      of methanol-water-formic acid (65:35:0.1, v/v/v). The HPLC system was then
      coupled to a MS-MS system with an atmospheric pressure ionisation interface in
      the positive ion mode. The chromatographed analytes were detected in the multiple
      reaction monitoring mode. The MS-MS ion transitions monitored were (m/z) 243-->86
      for molsidomine and 171-->86 for Sin-1. The method developed was validated. The
      absolute recoveries evaluated over the whole concentration range were 74 +/- 3
      and 55 +/- 5% for molsidomine and Sin-1, respectively. The method was found to be
      linear in the 0.5-50 ng/ml concentration range for the two analytes (r2 = 0.999
      for both molsidomine and Sin-1). The mean RSD values for repeatability and
      intermediate precision were 3.4 and 4.8% for moldsidomine and 3.1-7.7% for the
      metabolite. The method developed was successfully used to investigate the
      bioequivalence of oral doses of molsidomine between a generic tablet and a
      reference product.

PMID- 9781420
TI  - Determination of some aromatic amines in finger-paints for children's use by
      supercritical fluid extraction combined with gas chromatography.
AB  - A test method based on supercritical fluid extraction (SFE) and gas
      chromatography has been developed for some aromatic amines, such as 4-chloro-o
      toluidine, beta-naphthylamine and 4-aminobiphenyl. A two-level factor design was
      used as the optimization procedure. Four main variables were considered: CO2
      pressure, extraction temperature, static extraction time and volume of modifier
      (methanol). Results obtained for 4-chloro-o-toluidine, indicated that the volume
      of modifier was the variable with the most important influence on extraction, CO2
      pressure had a negative effect and temperature and time were less significant.
      For the other amines, static time was the most important variable in both cases,
      followed by CO2 pressure and volume of modifier, with no influence of
      temperature. SFE was compared with Soxhlet extraction, and was found to give
      higher recoveries in all cases. Other commercial finger-paints were tested for
      the presence of aromatic amines.

PMID- 9781419
TI  - High-performance liquid chromatographic determination of amphotericin B in plasma
      and tissue. Application to pharmacokinetic and tissue distribution studies in
      rats.
AB  - A sensitive HPLC method with piroxicam as internal standard was developed for
      assaying amphotericin B in plasma and tissue. An Ultrabase-C18 column and a
      simple mobile phase consisting of an acetonitrile-acetic acid (10%)-water
      (41:43:16) mixture were used. The flow-rate was 1 ml/min and the effluent was
      monitored at 405 nm. The linearity of the assay method was up to 1000 ng/ml and
      100 micrograms/g for plasma and tissue, respectively. Intra-day and inter-day
      RSDs were below 10% for all the sample types. This HPLC assay has been applied to
      determine amphotericin B in plasma and tissue samples taken during
      pharmacokinetic and tissue distribution studies in rats.

PMID- 9781422
TI  - 23rd Embryological Conference (Plants, Animals, Humans). Kiekrz-Poznan, Poland,
      13-16 May 1998. Abstracts.

PMID- 9781421
TI  - High-performance liquid chromatography-atmospheric-pressure chemical ionization
      mass spectrometry as a new tool for the determination of the mycotoxin
      zearalenone in food and feed.
AB  - A new method for the determination of the mycotoxin zearalenone (ZON) in food and
      feed, based on HPLC-MS with an atmospheric-pressure chemical ionization (APCI)
      interface after extraction from cereals and clean-up by either conventional solid
      phase or immunoaffinity cartridge is presented. The APCI interface parameters are
      optimized to provide detection of ZON with maximum sensitivity after RP
      separation of ZON on a C18 column with acetonitrile-water (40:60, v/v) at 1
      ml/min column flow without split. Using APCI-MS detection, the sensitivity of the
      method was improved by a factor of ca. 50 in comparison to HPLC with fluorescence
      detection, allowing determination of ZON down to 0.12 microgram/kg maize which is
      well below present threshold values. Due to the selectivity of MS detection, it
      also was possible to quantitatively determine ZON both in raw extracts without
      clean-up using a normal-size (100 mm) chromatographic column or using only a
      short (20 mm) chromatographic column, when a clean-up was done to minimize
      possible interferences.

PMID- 9781425
TI  - 4th AIMN Congress. Italian Association of Nuclear Medicine. Grado, May 16-19,
      1998. Abstracts.

PMID- 9781424
TI  - Long-term care for frail older people: reaching for the ideal system.
      International symposium. Tokyo, Japan, May 18-21, 1998. Abstracts.

PMID- 9781426
TI  - Diagnosis and management of surgical adrenal disorders.

PMID- 9781423
TI  - Drug Analysis '98. Joint meeting of the 6th International Symposium on Drug
      Analysis and 9th International Symposium on Pharmaceutical and Biomedical
      Analysis. Brussels, Belgium, 11-15 May 1998. Abstracts.

PMID- 9781428
TI  - Renal transplantation into augmented bladders.
AB  - BACKGROUND: Urinary bladder augmentation is gaining popularity for the treatment
      of dysfunctional bladders in renal transplant patients. Although reported cases
      of adult and pediatric transplants into the augmented bladder have been
      favorable, the potential risk of urinary tract infection and graft failure under
      immunosuppression is still disputable. We report our experiences with 4 patients
      who underwent renal transplantation into an augmented bladder. METHODS: Between
      1971 and 1996, 1275 renal transplants were performed at our institution. Of these
      transplants, 4 patients underwent renal transplantation into an augmented urinary
      bladder. Augmentation cystoplasty was performed before transplantation in 3
      patients and 7 years after transplantation in the other patient. The bladder was
      augmented with an ileal segment in 3 patients and a ureter in the fourth patient.
      Graft function was assessed by the serum creatinine level. Fluorocystometrograms
      were performed in all patients at fixed intervals. RESULTS: Posttransplant renal
      function was satisfactory overall and no patient exhibited proteinuria. All
      patients except 1 acquired a large capacity low pressure bladder and remained
      continent with clean intermittent catheterization. One patient who underwent
      ureterocystoplasty is still incontinent because of his relatively small bladder
      capacity. Posttransplant pyelonephritis was documented in 3 patients during the
      follow-up period, but no other complications were observed. CONCLUSIONS: Our
      study demonstrates that renal transplantation into extensively reconstructed
      bladders can be safely performed with good success. Although urinary tract
      infection is a major consideration, we recommend pretransplant reconstruction not
      only to preserve graft function, but also to achieve urinary continence.

PMID- 9781427
TI  - Significant prognostic factors for 5-year survival after curative resection of
      renal cell carcinoma.
AB  - BACKGROUND: Renal cell carcinoma (RCC) patients occasionally die of RCC even
      after curative resection. In this study, we investigated prognostic factors
      between survivors for more than 5 years and patients who died within 5 years
      after curative resection. METHODS: We retrospectively studied 111 patients who
      underwent RCC curative resection and were followed for more than 5 years. Patient
      survival at 5 years after curative resection was regarded as the end-point of
      this analysis. Statistical differences of 19 prognostic factors between surviving
      and deceased patients were determined using logistic regression analysis.
      RESULTS: Eighteen of the 111 patients died of RCC during the 5-year follow-up
      period. Of the 19 prognostic factors evaluated, univariate analysis showed
      significant differences in the body temperature, hemoglobin, erythrocyte
      sedimentation rate (ESR), alpha2-globulin, C-reactive protein (CRP), fibrinogen,
      tumor size, Robson's stage, T classification (renal capsular involvement),
      pathological grade, and mode of tumor infiltration. Five significant variables
      (body temperature, ESR, alpha2-globulin, fibrinogen, and tumor size) were
      excluded from multivariate analysis because greater than 10% of the data was
      missing. The TNM staging system was selected as the representative variable for
      stage for multivariate analysis. Using the remaining 5 significant variables
      (hemoglobin, CRP, T stage, pathological grade, and mode of tumor infiltration),
      multivariate analysis showed that CRP (P = 0.0126) and T stage (P = 0.0490) were
      the most important prognostic factors. CONCLUSION: From this analysis, CRP and
      renal capsular involvement were the most important factors predicting survival
      for greater than 5 years after curative resection of RCC.

PMID- 9781429
TI  - Kidney transplantation in patients with neurovesical dysfunction.
AB  - BACKGROUND: Five renal recipients with neurovesical dysfunction (NVD) were
      retrospectively reviewed focusing on anatomical and urodynamic abnormalities of
      the lower urinary tract and their management prior to kidney transplantation.
      METHODS: The underlying anomalies in these 5 patients were a posterior urethral
      valve (1 with an imperforate anus; n = 2), meningomyelocele (n = 2) and a
      congenital short urethra with an imperforate anus (n = 1). Their urinary tracts
      were evaluated prior to transplantation with voiding cystourethrography,
      urethrocystoscopy, cystometrography and electromyography of the external urethral
      sphincter to identify a possible focus of urinary tract infection, urine storage
      and voiding function. RESULTS: All 5 patients had NVD proven by urodynamic
      studies or by documentation of urinary retention in the absence of mechanical
      outlet obstruction. Bilateral high grade vesicoureteral reflux was noted in all
      patients, requiring ureteroneocystostomy. Clean intermittent catheterization
      (CIC) was ultimately employed for bladder emptying in all patients. Two patients
      with poor bladder compliance underwent augmentation cystoplasty before
      transplantation. The Mitrofanoff procedure was used in 2 patients with structural
      urethral abnormalities to access the bladder for catheterization. After
      eradication of possible sources of infection and establishment of a low-pressure
      urine storage system with bladder emptying by CIC, kidney transplantation was
      performed. Following kidney transplantation, all of the recipients were
      asymptomatic for urinary tract infections using CIC. Although 1 patient lost his
      graft due to chronic rejection, the other 4 other patients have good renal
      function. CONCLUSION: Kidney transplantation in patients with NVD can be
      performed provided that their urinary tract problems are properly resolved.

PMID- 9781430
TI  - Differential expression of hepatocyte growth factor in papillary and nodular
      tumors of the bladder.
AB  - BACKGROUND: The aim of this study was to investigate the expression of hepatocyte
      growth factor (HGF) and its receptor (c-met) during bladder tumorigenesis.
      METHODS: HGF and c-met expression were analyzed immunohistochemically in matched
      samples of normal, dysplastic, and carcinoma specimens from 49 human bladders
      resected at the time of radical cystectomy for nonmetastatic transitional cell
      carcinoma (TCC). The tumors were composed of papillary (n = 22), nodular (n = 16)
      or mixed papillary and nodular (mixed; n = 11) components. RESULTS: The normal
      urothelium showed no significant immunoreactivity to HGF. Expression of HGF was
      observed in 45.5%, 77.3% and 90.9% of specimens demonstrating mild, moderate, and
      severe dysplastic lesions adjacent to papillary TCCs, respectively, whereas all
      of the papillary TCC samples were positive for HGF. No immunoreactivity for HGF
      was found in dysplastic lesions from nodular tumors, and only 2 specimens had
      positive immunostaining for HGF in the tumor areas (1 showed weak immunostaining
      and 1 showed HGF immunostaining only in the deeper invasive compartment).
      Additionally, 3 nodular lesions taken from mixed tumors showed weak
      immunostaining for HGF while the concurrent papillary lesions were HGF-positive.
      There was a significant difference of HGF immunoreactivity between papillary and
      nodular tumors (P < 0.01). c-met immunostaining was consistently detected in all
      specimens. HGF and c-met immunoreactivity did not significantly correlate with
      tumor stage and grade, nor with overall patient survival irrespective of the
      tumor growth pattern. CONCLUSION: These results suggest that HGF expression may
      play a significant role in the development of papillary TCC.

PMID- 9781431
TI  - Prospective randomized comparative study of antibiotic prophylaxis in
      urethrocystoscopy and urethrocystography.
AB  - BACKGROUND: There has been a great deal of discussion regarding the necessity of
      the prophylactic use of antibiotics in transurethral procedures. In order to
      clarify this complicated issue, a randomized prospective study was performed for
      patients undergoing urethrocystoscopy or urethrocystography. PATIENTS AND
      METHODS: Patients who underwent urethrocystoscopy or urethrocystography and did
      not have pyuria and bacteriuria were included and divided randomly into 2 groups,
      either receiving a prophylactic antibiotic or no antibiotic. For antibiotic
      prophylaxis, 200 mg of sparfloxacin or fleroxacin were administered within a 1
      hour period before the urethrocystoscopic or urethrocystographic examination,
      respectively. Analyses were performed on patients who were seen within 1 month
      after the examination, using the appearance of pyuria, bacteriuria, or a febrile
      infection as the endpoint. RESULTS: Of 47 patients undergoing urethrocystoscopy,
      45 were eligible for analysis, and of these, sparfloxacin was administered to 21
      patients. Thirty-three of 37 patients undergoing urethrocystography were eligible
      for analysis with fleroxacin administered to 16 patients. There were no
      significant differences in the background factors between the 2 groups undergoing
      either transurethral examination. None of the patients in either group developed
      pyuria, bacteriuria or a febrile infection after the examination. CONCLUSIONS:
      Prophylactic administration of antibiotics is not necessarily essential in
      urethrocystoscopy or urethrocystography in patients with sterile urine.

PMID- 9781432
TI  - Elevated stress protein in transitional cells exposed to urine from interstitial
      cystitis patients.
AB  - BACKGROUND: It has been hypothesized that urine from interstitial cystitis (IC)
      patients may contain one or more toxic factors not present in "normal" urine.
      Bladder tissues exposed to these toxic factors could have elevated stress
      proteins. If this assumption is correct, stress protein levels could be a useful
      marker for identifying patients at risk for developing this syndrome. METHODS: To
      experimentally investigate this possibility, a sensitive assay (ELISA) was used
      to measure levels of the 72 kDa stress protein in urothelial target cells after
      in vitro exposure to urine from IC patients. RESULTS: We observed a modest 12%
      increase in 72 kDa stress protein in cells treated with urine from IC patients
      compared to cells exposed to normal urine (1.12 compared to 0.99 ng/microg
      extracted protein; P < 0.05). In addition, it was possible to demonstrate the 72
      kDa stress protein in histologic sections obtained from mucosal biopsies of IC
      patients. Stress protein was located primarily in the surface urothelial cells of
      the mucosa. CONCLUSIONS: These results seem to indicate that stress protein could
      play an important protective role at this particular site. They further suggest
      that IC urine is more toxic than normal urine and, in contact with underlying
      urothelial and deeper bladder tissue, may upregulate genes involved in stress
      protein responses. This may be an important concept in the etiology of IC.

PMID- 9781433
TI  - Study of the effect of vesical filling and voiding on ureterovesical junctions
      and internal urethral meatus: the filling and meato-vesico-ureteral reflexes.
AB  - BACKGROUND: The effect of vesical filling and voiding on bladder pressure, the
      ureterovesical junctions (UVJs), and the internal urethral meatus (IUM) was
      studied. METHODS: A pressure catheter was introduced into each of the UVJs, the
      IUM, and the urinary bladder of 16 healthy volunteers (9 men, 7 women; mean age,
      38.4 years) and their pressure response to vesical filling in increments of 50 mL
      and during voiding as well as on IUM distension was recorded. The tests were
      repeated after separately anesthetizing the bladder, UVJs, and IUM. RESULTS: When
      the bladder was filled to 250 mL, there was a significant increase (P < 0.01) in
      the pressure of the UVJs, IUM, and bladder, which continued to rise with bladder
      filling up to 350 mL (P < 0.001). There was no further pressure increase above
      350 mL. During voiding, the bladder and UVJs pressures rose (P < 0.0001) while
      the IUM pressure dropped (P < 0.01). IUM distension caused a significant pressure
      rise in the bladder and UVJs and a drop of IUM pressure. These pressure responses
      did not occur upon separate anesthetization of the bladder, UVJs, or IUM.
      CONCLUSIONS: A reflex relationship appears to exist between vesical filling and
      an increase in UVJs and IUM pressure which was absent on anesthetizing the
      presumed 2 arms of the reflex arc, the filling reflex. Another reflex
      relationship may exist between IUM dilatation and the bladder and UVJs pressure
      increase, the meato-vesico-ureteral reflex. These 2 reflexes might help further
      delineate the mechanism of micturition.

PMID- 9781434
TI  - Preoperative predictors for organ-confined disease in Japanese patients with
      stage T1c prostate cancer.
AB  - BACKGROUND: In order to define the characteristics of patients with clinical
      stage T1c prostate cancer in Japan, clinicopathologic data obtained from patients
      treated by radical prostatectomy were reviewed. METHODS: Fifty-four stage T1c
      cancers were evaluated for tumor volume, Gleason grade, tumor location and
      pathologic stage from prostatectomy specimens in association with preoperative
      clinical parameters. RESULTS: The mean tumor volume was 3.94 mL (range, 0.07 to
      33.4 mL), and 11 of the 54 tumors had a tumor volume of less than 0.5 mL. Thirty
      two tumors (59%) were organ-confined, while 7 (13%) involved the seminal vesicle
      and/or regional lymph nodes. Multivariate logistic regression analysis of the
      pretreatment variables, including age, pretreatment PSA level, prostate volume,
      biopsy grade, and number of cancer-positive cores revealed that the serum PSA
      level and the number of cancer-positive biopsy cores were independent factors to
      predict organ-confined tumors (P = 0.036 and 0.044, respectively). For T1c cancer
      with less than 4 cancer-positive biopsy cores, the sensitivity and specificity
      for predicting organ-confined tumors were 90% and 70%, with a cut-off value of 17
      ng/mL for the serum PSA level. CONCLUSION: The clinicopathologic features of T1c
      prostate cancer in Japanese patients were similar to those of whites reported
      elsewhere. Both serum PSA levels and the number of positive biopsy cores may be
      useful as pretreatment parameters to identify patients with the potential to
      benefit from radical treatment.

PMID- 9781435
TI  - Incidence of lymph node metastasis and its impact on long-term prognosis in
      clinically localized prostate cancer.
AB  - BACKGROUND: Pelvic lymph node dissection (PLND) is an important staging method
      for men with clinically localized prostate cancer. We report our experience with
      staging PLND and the impact of lymph node metastasis on long-term prognosis.
      METHODS: One hundred forty-eight consecutive patients who underwent staging PLND
      for clinically localized prostate cancer were retrospectively studied. Patients
      were evaluated for the presence and number of lymph node metastases, treatment
      (prostatectomy vs. radiotherapy), and endocrine therapy, and analyzed with
      respect to disease progression and survival. The mean follow-up period was 52.9
      months (range, 2.3 to 165.8 months). RESULTS: Thirty-two patients (21.6%) had
      pelvic lymph node metastases, the incidence of which markedly decreased from
      32.3% in 1982 to 1987 to 6.7% in 1994 to 1997. The intervals to disease
      progression and cancer death were significantly shorter in patients with positive
      lymph nodes (P < 0.001). In stage D1 disease, patients who underwent a radical
      prostatectomy tended to be free of progression longer than those receiving
      radiotherapy or conservative therapy (P = 0.0546). Other factors, such as early
      endocrine therapy, the extent of lymph node involvement and the Gleason score of
      the primary tumor did not predict disease progression or survival. CONCLUSION:
      These data suggest a decreasing trend in the incidence of lymph node metastasis
      in the PSA era. Although longer disease-free intervals were observed in radical
      prostatectomy-treated patients, the impact of an aggressive approach to stage D1
      disease awaits further studies.

PMID- 9781436
TI  - Clinical significance of interruption of therapy with allylestrenol in patients
      with benign prostatic hypertrophy.
AB  - BACKGROUND: A multicenter, clinical trial investigated the effects of an
      interruption of antiandrogen therapy on subjective and objective clinical
      parameters in patients with benign prostatic hypertrophy (BPH). METHODS: Patients
      were given antiandrogen therapy with allylestrenol (50 mg/day) for 16 weeks. The
      medication was then withheld and the patients were carefully monitored for an
      additional 16 weeks. There were 34 BPH patients ranging in age from 55 to 82
      years (mean, 66.1 years). The efficacy of allylestrenol was evaluated by its
      effects on prostate volume, maximum urinary flow rate (MFR), and symptom scores
      at the end of 16 weeks of treatment and then again at 32 weeks (16 weeks after
      cessation of therapy). RESULTS: Allylestrenol was effective in the treatment of
      BPH, and was still effective 16 weeks after the cessation of medication. The
      prostate volume did not change after treatment cessation nor did the total
      symptom score, but the MFR reversed to the pretreatment level. Serum testosterone
      (1.95 ng/mL), dihydrotestosterone, and gonadotropin levels decreased on therapy,
      but were completely reversed by the end of this study. A prostate needle biopsy
      revealed that after 16 weeks without therapy, some glands showed regressive
      glandular changes, while some glands showed slight hyperplastic changes of the
      secretory epithelium. Eight per cent of patients complained of loss of libido
      during this study. CONCLUSIONS: Allylestrenol is an effective and safe medical
      treatment for patients with symptomatic BPH. Hormonal and histopathologic
      findings suggest that the prostate gland may regrow after discontinuation of
      medication.

PMID- 9781437
TI  - Reduced chlamydial infection and gonorrhea among commercial sex workers in
      Fukuoka City, Japan.
AB  - BACKGROUND: Until recently, epidemiologic studies of sexually transmitted
      diseases (STDs), including human immunodeficiency virus type-1 (HIV-1) infection,
      among Japanese female commercial sex workers and their patterns of condom use
      have been rare. We investigated trends in STDs among female commercial sex
      workers and their condom use patterns in Fukuoka, Japan, from 1990 through 1995.
      METHODS: The study group consisted of 1218 female commercial sex workers who
      attended an STD clinic to undergo screening for major STDs including chlamydial
      infection, gonorrhea and HIV-1 infection from 1990 through 1995. Endocervical
      smear specimens were taken from the women to detect Chlamydia trachomatis and
      Neisseria gonorrhoeae, and blood samples were obtained for the serologic
      diagnosis of HIV-1. Also, the commercial sex workers were interviewed concerning
      their condom use patterns. RESULTS: The annual infection and detection rates of
      C. trachomatis declined significantly from 58.1% in 1990 to 46.2% in 1995 and
      from 16.3% in 1990 to 10.0% in 1995, respectively, while the annual infection and
      detection rates of N. gonorrhoeae also declined significantly from 13.2% in 1990
      to 3.5% in 1995 and from 1.5% in 1990 to 0.4% in 1995, respectively. None were
      found to be seropositive for HIV-1 during the 6-year period. The proportion of
      commercial sex workers using condoms significantly increased during 1992-1993 and
      1994-1995 periods, as compared with the 1990-1991 period. CONCLUSION: Reductions
      in the prevalence of major STDs among female commercial sex workers may be
      related to an increase in the frequency of condom use.

PMID- 9781438
TI  - Immunological analysis of rat renal transplant recipients exhibiting long-term
      survival following treatment with 15-deoxyspergualin in the early postoperative
      phase.
AB  - BACKGROUND: We previously reported that short-term administration of 15
      deoxyspergualin (DSG), 5 mg/kg/day on postoperative days 4 through 7, prolonged
      survival of rat renal allografts indefinitely. We now report the immunologic
      environment of DSG-treated recipients in the early postoperative phase. METHODS:
      TO (RT1u) rat kidneys were transplanted into WKAH (RT1k) rats. Peripheral blood
      lymphocytes (PBL), splenocytes (SPC) and graft infiltrating lymphocytes (GIL)
      were harvested from rejecting (untreated) recipients on day 7 (group AR) and from
      DSG-treated recipients on days 7 (Group DSG7) and 14 (group DSG14). Flow
      cytometric analysis was done to determine characteristics of these cells. Mixed
      lymphocyte culture reactions (MLRs) were also studied to examine suppressive
      activities of sera, SPC, and GIL of each group by adding them to TO/WKAH MLRs.
      RESULTS: In all groups, the proportions of CD8- and interleukin 2 receptor (IL
      2R)-positive cells were higher for GIL than for either PBL or SPC. The CD4/CD8
      ratio was lowest in GIL. Comparing groups DSG7 and DSG14, significant decreases
      in the proportion of CD8- and IL-2R-positive cells were found only in GIL. Sera
      of all groups nonspecifically suppressed MLRs, independent of DSG-administration.
      GIL of all groups also nonspecifically suppressed MLRs, while these suppressive
      activities were not observed with SPC. Suppressive activities of GIL remained
      unchanged in the first 2 postoperative weeks. CONCLUSIONS: Differences in the
      immunologic environment were reflected primarily in GIL. DSG seemed to decrease
      CD8- and IL-2R-positive cells in allografts. In the presence of DSG, this model
      may feature a predominance of nonspecific suppressor T cells over cytotoxic T
      cells during the first 2 postoperative weeks.

PMID- 9781440
TI  - Ileal pouch with an umbilical stoma: a continent mechanism created by the
      extramural tunnel technique.
AB  - We present an initial experience of creating an extramural continent valve in the
      ileal pouch in 4 patients who required continent urinary diversion. Using the
      appendix or a tapered ileal segment, the continent valve was created by the
      extramural tunnel technique along the anterior suture line of the pouch to
      facilitate the umbilical anastomosis. All patients were continent postoperatively
      with easy catheterization. This technique can provide a simple and effective
      continent pouch formed entirely from the ileum.

PMID- 9781439
TI  - Activation of the Ca2+-activated K+ channel via protein kinase A-dependent
      phosphorylation in human prostatic smooth muscle cells.
AB  - BACKGROUND: We investigated the functional importance of the Ca2+-activated K+
      channel (K(Ca)-channel) of human prostatic smooth muscle cells in cyclic
      adenosine 3',5'-monophosphate (cAMP)-induced relaxation, to clarify signal
      transduction pathways and intracellular mechanisms of relaxation in prostatic
      smooth muscle. METHODS: Using the patch-clamp technique, we characterized the
      K(Ca)-channel of cultured human prostatic smooth muscle cells. We also
      investigated the effects on the K(Ca)-channels of forskolin, an activator of
      adenylate cyclase, amrinone, a phosphodiesterase inhibitor, and protein kinase A
      (A-kinase)-dependent phosphorylation. RESULTS: Single-channel current recordings
      from cultured human prostatic smooth muscle cells revealed the presence of K(Ca)
      channels (conductance 296.7 +/- 5.67 pS, n = 7). In cell-attached patch
      configurations, the K(Ca)-channel was activated by forskolin (10(-4) mol/L) and
      amrinone (10(-4) mol/L). In inside-out patch configurations, it was activated by
      catalytic subunits of A-kinase (10 U/mL). CONCLUSIONS: We conclude that the K(Ca)
      channel of human prostatic smooth muscle cells is regulated by intracellular cAMP
      levels and that A-kinase mediates the cAMP-induced activation of the K(Ca)
      channel. This regulation of the K(Ca)-channel by cAMP may at least partially
      explain cAMP-induced prostatic smooth muscle relaxation and the effectiveness of
      certain drugs for treatment of obstruction in benign prostatic hyperplasia.

PMID- 9781441
TI  - Non-synchronous double adenoma of the parathyroid gland.
AB  - A 46-year-old female underwent an excision of a parathyroid adenoma diagnosed as
      recurrent primary hyperparathyroidism 24 years after the initial excision of a
      parathyroid adenoma. We report a case of non-synchronous double adenomas of the
      parathyroid glands documented histopathologically.

PMID- 9781442
TI  - Erythropoietin-producing renal cell carcinoma arising from acquired cystic
      disease of the kidney.
AB  - A 49-year-old woman had been on hemodialysis for 18 years. She presented with
      left back pain and macrohematuria. Radiologic studies demonstrated a left renal
      tumor with acquired cystic disease of the kidney. Her serum erythropoietin (EPO)
      level was 78.4 U/L despite no history of EPO supplementation. Left radical
      nephrectomy was performed. Pathologic examination revealed EPO-producing renal
      cell carcinoma. After surgery, the patient's serum EPO level decreased markedly
      to 15.1 U/L. The measurement of serum EPO levels may be useful for detecting and
      monitoring a recurrence of renal cell carcinoma with acquired cystic disease of
      the kidney in patients on long-term hemodialysis.

PMID- 9781443
TI  - Schwannoma of the urinary bladder: a case report.
AB  - The urinary bladder is an extremely rare site for primary schwannomas. They are
      most often associated with von Recklinghausen disease. This patient was found to
      have a schwannoma of the bladder in the absence of evidence of von Recklinghausen
      disease and was successfully treated with a partial cystectomy. This represents
      only the third such case in the literature of this entity.

PMID- 9781444
TI  - Abdominal actinomycosis misdiagnosed as a secondary bladder tumor: a case report.
AB  - A 46-year-old woman presented with a hypogastric mass. The preoperative diagnosis
      was a malignant ovarian tumor involving multiple organs, including the urinary
      bladder. Surgical exploration was performed with wide resection of the right
      ovary and uterus, including the affected ileum, sigmoid colon, and omentum. An
      intraoperative histopathological examination of the paravesical tissue revealed
      abdominal actinomycosis. Consequently, bladder resection was not done. The cause
      of abdominal actinomycosis in this patient was probably due to implantation of an
      intrauterine device 3 years previously.

PMID- 9781445
TI  - Testis sparing surgery for infantile synchronous bilateral teratoma of the
      testis.
AB  - We report a rare case of infantile synchronous bilateral testicular teratoma
      treated by testis sparing surgery. Preoperative ultrasonography, tumor marker
      status and intraoperative findings were suggestive of benign neoplasia. Under
      these circumstances we performed high orchiectomy for the left testis and testis
      sparing surgery for the right. Surgical treatment of teratoma in childhood is
      controversial, especially when it occurs bilaterally. In this report we discuss
      testis sparing surgery as the treatment for this disease.

PMID- 9781446
TI  - Acquired undescended testis.
AB  - We report an unusual case of a 22-year-old man who presented with the left testis
      spontaneously ascended to a non-scrotal position. The testis had been documented
      to be intrascrotal without any sign of up-migration when the man was 12 years
      old. On surgery, the cryptorchid testis was found to be located within the
      superficial inguinal pouch. The testis was atrophic with the spermatic cord too
      short. On dissection, a remnant string of the closed processus vaginalis was
      observed within the cord, and the distal end of the gubernaculum was abnormally
      attached to the fascia near inguinoscrotal junction. Histopathologic findings of
      the testis were that of the Sertoli-cell-only syndrome which may represent the
      end-stage of germinal cell hypoplasia, a pathologic sequela common in
      postpubertal undescended testis. We recommend 3 diagnostic criteria for the
      acquired undescended testis and emphasize that testicular descent should be
      confirmed in infancy and re-confirmed periodically through puberty by the health
      care physician. Our observations seem to support the theory that acquired
      undescended testis may be caused by a postnatal failure of the spermatic cord to
      elongate in proportion to somatic growth.

PMID- 9781447
TI  - Polymerase chain reaction analysis of the Y chromosome long arm in azoospermic
      patients: lack of the Y chromosome recognition motif (YRRM1) gene.
AB  - We analyzed DNA from a patient with azoospermia whose Y chromosome was
      cytogenetically normal. A total of 16 loci on the Y chromosome long arm were
      examined: 15 loci between DYS7E and DYZ1, and the Y chromosome RNA recognition
      motif (YRRM1) locus, a candidate gene for the azoospermic factor AZF. We did not
      detect the YRRM1 gene in this patient. This finding supports the theory that
      YRRM1 is an essential gene for spermatogenesis.

PMID- 9781448
TI  - Establishment of a monoclonal antibody (1/14/16H9) for detection of equine
      keratan sulfate.
AB  - OBJECTIVES: To establish a sensitive and specific monoclonal antibody (MAB)
      against equine keratan sulfate (KS) and to develop an enzyme immunoassay for
      measurement of the concentration of KS in serum and synovial fluid from horses.
      SAMPLE POPULATION: 18 synovial fluid and 48 serum samples were obtained from
      clinically normal horses and horses with arthritis. PROCEDURE: BALB/c mice were
      immunized with chondroitinase-ABC-digested proteoglycan monomer from equine joint
      cartilage, and MAB were raised, using Sp2/O cells as a fusion partner. A
      competitive ELISA was optimized, using one of the established MAB, and KS
      concentration in synovial fluid and sera from horses was measured. RESULTS: The
      high-titer MAB1/14/16H9, which specifically recognizes the epitope on equine KS,
      was identified. This antibody had no reactivity with chondroitin sulfate and core
      protein of proteoglycan monomers, hyaluronan, heparin, dermatan sulfate, and
      heparan sulfate. A competitive ELISA for determination of KS concentration was
      optimized, using this antibody. Precision data were obtained for the range of 10
      to 160 ng/ml. The within- and between-assay coefficients of variation were 10.0
      and 12.7%, respectively. CONCLUSIONS: MAB 1/14/16H9 that specifically recognized
      equine KS was established and was used to develop an enzyme immunoassay for
      measurement of the concentration of KS in synovial fluid and sera from horses. It
      is expected that the assay system using MAB 1/14/16H9 will contribute to
      evaluation of cartilage metabolic activity in horses.

PMID- 9781449
TI  - Morphometric analysis of endometrial periglandular fibrosis in mares.
AB  - OBJECTIVES: To develop an objective, quantifiable assay for endometrial
      periglandular fibrosis (EPF) and correlate assay results with histologic and
      ultrastructural changes in equine endometrial biopsy specimens. SAMPLE
      POPULATION: Endometrial biopsy specimens from 70 mares from 3 to 27 years old in
      estrus. PROCEDURE: In a double-blinded study design, endometrial biopsy specimens
      were graded histologically (modified Kenney classification) for EPF and
      inflammation. Endometrial periglandular collagen volume fraction (%EPCVF) was
      determined by light microscopic image analysis of picrosirius red-stained
      sections. Specimens from selected mares were examined by transmission electron
      microscopy. RESULTS: %EPCVF values varied significantly among the 4 modified
      Kenney EPF categories (I, IIA, IIB, and III) and increased with increasing age of
      mares. Morphologically, EPF consisted of concentric layers of transformed
      fibroblasts with myofibroblastic features and deposition of fibrillar collagen
      around unaltered glandular basal laminae. CONCLUSIONS AND CLINICAL RELEVANCE:
      %EPCVF correlates well with morphologic changes in endometrial biopsy specimens.
      Determination of %EPCVF could be useful in evaluation and clinical management of
      subfertile mares and in investigations of the pathogenesis of EPF.

PMID- 9781450
TI  - Detection of Haemobartonella felis in cats with experimentally induced acute and
      chronic infections, using a polymerase chain reaction assay.
AB  - OBJECTIVE: To develop a test for detection of Haemobartonella felis, using a
      polymerase chain reaction (PCR) assay. ANIMALS: 4 adult cats seronegative for
      FeLV and feline immunodeficiency virus. PROCEDURE: Cats were infected with H
      felis by i.v. administration of 1 ml of blood obtained from an infected cat.
      Rectal temperature, PCV, and microscopic examination of blood smears for
      organisms were monitored daily. At peak of infection, doxycycline treatment was
      initiated for 21 days. Blood samples were collected at weekly intervals. Six
      months after treatment, 2 cats were given methylprednisolone (14 mg/kg of body
      weight, i.m.). Daily blood samples were collected for CBC, detection of
      organisms, and PCR evaluation. On the basis of the 16S rRNA gene sequence of H
      felis, specific PCR primers were created for a 393-basepair internal fragment.
      RESULTS: The 393-basepair product was consistently amplified from blood samples
      obtained during peak parasitemia but not during the last week of or immediately
      after completion of doxycycline treatment. After treatment, PCV returned to the
      reference range, and organisms were not observed in blood samples; however, the
      PCR product could be consistently amplified. After administration of
      methylprednisolone, organisms were only rarely observed in blood smears but were
      consistently detected by PCR analysis. CLINICAL RELEVANCE: Using PCR analysis, it
      was possible to detect H felis in blood samples obtained from cats during peak
      parasitemia, during most of the carrier phase, and after challenge with
      immunosuppressive drugs. During and immediately after antibiotic treatment, this
      test may fail to detect the organisms.

PMID- 9781451
TI  - Use of laser flare-cell photometry to count anterior chamber canine leukocytes
      and latex beads in vitro.
AB  - OBJECTIVE: To determine whether the cell measuring function of a laser flare-cell
      photometer is accurate and reproducible, using an in vitro model. SAMPLE
      POPULATION: Leukocytes from 8 clinically normal Beagles. PROCEDURE: Latex beads
      11.9 and 6.4 microm in diameter were used to simulate canine WBC and RBC,
      respectively. Beads were diluted to known concentrations, placed in a model eye,
      and counted by use of the laser flare-cell photometer. A range of protein
      diluents from 0 to 2,000 mg/dl was used to suspend beads and simulate anterior
      uveitis, when cells and protein would be in the aqueous humor. A similar series
      of experiments were repeated, using leukocytes isolated from the blood of
      Beagles. RESULTS: The laser flare-cell photometer can count 6.4-microm beads
      reproducibly and linearly up to a total of 510 cells/mm3, and 11.9-microm beads
      up to 1,300 cells/mm3 over a protein range of 0 to 2,000 mg/dl. The instrument
      can also count canine leukocytes reproducibly and linearly up to 1,300 cells/mms
      over that protein range. CONCLUSIONS AND CLINICAL RELEVANCE: Cell and bead sizes
      and concentrations and protein concentrations were chosen to mimic the range
      observed in dogs with uveitis. Because the laser flare-cell photometer accurately
      counted these cells in a range of protein concentrations in the model eye, it has
      the potential for use in noninvasive quantitative evaluation and monitoring of
      uveitis in dogs.

PMID- 9781452
TI  - Effects of acepromazine and butorphanol on positive-contrast upper
      gastrointestinal tract examination in dogs.
AB  - OBJECTIVE: To determine whether acepromazine (ACE) and butorphanol (BUT)
      combination can be used for restraint of dogs during positive-contrast upper
      gastrointestinal tract (UGIT) examination. ANIMALS: 6 healthy dogs. PROCEDURE: In
      a randomized crossover design study, weekly UGIT examinations were performed on
      each dog for 5 weeks after administration of normal saline solution (0.5 ml),
      xylazine (1.0 mg/kg of body weight), or a combination of ACE (0.1 mg/kg) and 1 of
      3 doses of BUT (0.05, 0.2, 1.0 mg/kg). Gastrointestinal tract emptying time, GI
      motility, pulse, respiratory rate, and quality of restraint were assessed.
      RESULTS: Total gastric emptying time was significantly prolonged by use of an ACE
      and BUT (0.05 mg/kg) combination. Xylazine and higher dosages of BUT
      significantly prolonged gastric and intestinal emptying times. All anesthetic
      protocols significantly decreased motility and facilitated nonmanual restraint.
      Xylazine and BUT (1.0 mg/kg) significantly decreased pulse and respiratory rate.
      CONCLUSION: The ACE and BUT combination prolonged GI tract emptying times,
      decreased GI motility, and facilitated nonmanual restraint for duration of the
      examination. Although GI motility was decreased and total gastric emptying time
      was prolonged, administration of ACE (0.1 mg/kg) plus BUT (0.05 mg/kg) allowed
      morphologic examination of the GI tract within 5 hours. Xylazine prolonged GI
      tract emptying, decreased GI motility, and provided good to excellent initial
      restraint. Clinical Relevance-The ACE and BUT combination prohibits functional
      examination of the GI tract; however, morphologic examination is possible when
      low dosages of BUT (0.05 mg/kg) are used.

PMID- 9781453
TI  - Changes in plasma protein concentrations in ponies with experimentally induced
      alimentary laminitis.
AB  - OBJECTIVE: To determine whether plasma protein concentrations were altered in
      ponies with alimentary laminitis. ANIMALS: 12 adult ponies. PROCEDURE: Acute
      laminitis was induced in 6 ponies by oral administration of carbohydrate (85%
      corn starch, 15% wood flour); the other 6 ponies were used as controls. A
      physical examination was performed and blood samples were collected immediately
      before and 4, 8, 12, 24, and 28 hours after administration of carbohydrate.
      Plasma protein concentrations were determined by means of sodium dodecyl sulphate
      polyacrylamide gel electrophoresis. RESULTS: 19 plasma proteins ranging from a
      molecular weight of 24,000 to a molecular weight of 350,000 were identified in
      all 12 ponies. Plasma concentrations of proteins with molecular weights of
      350,000 (fibrinogen), 130,000 (ceruloplasmin), 118,000 (c-reactive protein),
      67,000 (alpha1-antitrypsin I), 65,000 (alpha1-antitrypsin II), 50,000
      (haptoglobulin), and 45,000 (acid glycoprotein) were significantly increased in
      ponies with laminitis, compared with concentrations in control ponies.
      CONCLUSION: Changes in plasma protein concentrations are detectable within 4
      hours after the onset of alimentary laminitis in ponies. Clinical Relevance
      Measurement of plasma protein concentrations may be useful in monitoring the
      progression of laminitis in ponies.

PMID- 9781454
TI  - Computer-assisted image analysis of intratumoral vessel density in mammary tumors
      from dogs.
AB  - OBJECTIVE: To determine whether intratumoral microvessel density can be used to
      distinguish benign from malignant mammary tumors in dogs and to predict the
      outcome of surgical treatment for small volume (< 3-cm diameter) tumors. SAMPLE
      POPULATION: Tissue sections from 58 mammary tumors (42 malignant and 16 benign)
      from dogs. PROCEDURE: Mammary tumors were stained by immunohistochemistry for
      factor VIII-related antigen. Computer-assisted image analysis was used to
      determine intratumoral vessel density in immunostained areas. Total vascular
      density (TVD), calculated from 3 non-overlapping fields, was analyzed for
      correlation with patient or tumor histomorphologic characteristics, and results
      obtained by surgical treatment of small volume tumors. RESULTS: Mean TVD of
      malignant tumors was significantly greater than that of benign tumors. Total
      vascular density was not correlated with patient age, sex, reproductive status,
      clinical tumor stage, or histologic type. For small volume (< 3-cm diameter)
      malignant tumors, mean TVD was higher in tumors that recurred after surgery than
      in tumors that did not recur; however, TVD was not predictive of time to
      recurrence. CONCLUSION AND CLINICAL IMPLICATIONS: Immunohistochemistry and
      computer-assisted image analysis allowed objective quantitation of intratumoral
      microvessel density in formalin-fixed, paraffin-embedded tissue sections. Tumors
      with high TVD were more likely to recur after surgical treatment than tumors with
      low TVD suggesting that TVD measurements can be used by the clinician, in
      addition to histologic type and clinical stage, to predict prognosis after
      surgical treatment. These data also provide rationale for use of antiangiogenesis
      strategies for treatment of malignant mammary tumors in dogs.

PMID- 9781455
TI  - Shear-induced platelet activation and platelet-neutrophil aggregate formation by
      equine platelets.
AB  - OBJECTIVES: To determine whether platelets become activated and form platelet
      platelet or platelet-neutrophil aggregates, or both, when subjected to shear.
      SAMPLE POPULATION: Blood obtained from 3 Thoroughbreds. PROCEDURES: Blood, with
      PCV adjusted to 32 (low hematocrit) or 60 (high hematocrit)%, was subjected to
      shear rates of 11.25, 22.5, 45, 90, 225, and 750/s for 3 minutes by use of a cone
      plate viscometer. Flow cytometric techniques were used to identify activated
      platelets, platelet-platelet aggregates, and platelet-neutrophil aggregates.
      RESULTS: Shear resulted in decreased platelet count, increased mean platelet
      volume, platelet activation, and formation of platelet-platelet and platelet
      neutrophil aggregates. These changes occurred at lower shear rates in blood with
      high hematocrit. Platelet-neutrophil aggregate formation was inhibited by
      blocking P-selectin, but not CD11/CD18 receptors. CONCLUSIONS: Shear-induced
      platelet activation and aggregate formation occur at physiologic shear rates.
      CLINICAL RELEVANCE: Shear-induced platelet activation may explain the exercise
      associated platelet-neutrophil aggregates observed in Thoroughbreds undergoing
      treadmill exercise.

PMID- 9781456
TI  - Hematologic and serum biochemical variables and plasma corticotropin
      concentration in healthy aged horses.
AB  - OBJECTIVES: To compare hematologic and serum biochemical variables and plasma
      ACTH concentration between healthy horses 5 to 12 years old and those more than
      20 years old. ANIMALS: 30 healthy horses 5 to 12 years old and 30 healthy horses
      more than 20 years old. PROCEDURES: Venous blood was collected from all horses,
      and CBC and serum biochemical analysis were performed for each horse. Plasma ACTH
      concentration was determined by radioimmunoassay. Student's paired t-test or the
      Mann-Whitney rank sum test was used to compare values between control and aged
      horse groups. RESULTS: Compared with values for control horses, aged horses had
      significantly higher erythrocyte mean cell volume and mean cell hemoglobin. Aged
      horses also had significantly decreased total lymphocyte count. Five aged horses
      had lymphocyte count that was lower than the low reference limit as established
      for horses in our laboratory. Differences between control and aged horses for
      serum biochemical or plasma ACTH values were not significant. CONCLUSION:
      Compared with younger adult horses, those more than 20 years old have some
      hematologic differences, but there is no apparent effect of aging on baseline
      plasma ACTH concentration. CLINICAL RELEVANCE: It is important to establish age
      matched control values for optimal interpretation of clinicopathologic variables.

PMID- 9781457
TI  - Morphologic and cytochemical characteristics of blood cells from Hawaiian green
      turtles.
AB  - OBJECTIVE: To identify and characterize blood cells from free-ranging Hawaiian
      green turtles, Chelonia mydas. SAMPLE POPULATION: 26 green turtles from Puako on
      the island of Hawaii and Kaneohe Bay on the island of Oahu. PROCEDURE: Blood was
      examined, using light and electron microscopy and cytochemical stains that
      included benzidine peroxidase, chloroacetate esterase, alpha naphthyl butyrate
      esterase, acid phosphatase, Sudan black B, periodic acid-Schiff, and toluidine
      blue. RESULTS: 6 types of WBC were identified: lymphocytes, monocytes,
      thrombocytes, heterophils, basophils, and eosinophils (small and large).
      Morphologic characteristics of mononuclear cells and most granulocytes were
      similar to those of cells from other reptiles except that green turtles have both
      large and small eosinophils. CONCLUSIONS: Our classification of green turtle
      blood cells clarifies improper nomenclature reported previously and provides a
      reference for future hematologic studies in this species.

PMID- 9781458
TI  - Evaluation of physiologic indices in mice vaccinated with protein-ergotamine
      conjugates and fed an endophyte-infected fescue diet.
AB  - OBJECTIVES: To assess effects of vaccination against fescue toxicosis on weight
      gain, serum prolactin and cholesterol concentrations, and alkaline phosphatase
      (ALP) activity in mice fed an endophyte-infected (EI) or endophyte-free (EF)
      fescue diet. ANIMALS: 50 six-week-old male BALB/c mice. PROCEDURE: Mice were
      randomly allocated to the following 5 groups: 1, vaccinated intraperitoneally
      with a bovine serum albumin-ergotamine (EG) conjugate and fed an EI fescue diet;
      2, orally vaccinated with cholera toxin (CT) subunit B-EG conjugate mixed with
      free CT and fed an EI fescue diet; 3, not vaccinated and fed an EI fescue diet;
      4, passively vaccinated with monoclonal antibodies specific for ergovaline (EV)
      and fed an EI fescue diet; and 5, not vaccinated and fed an EF fescue diet.
      RESULTS: Antibodies against EG and EV were in serum of mice of groups 1 and 4,
      respectively. Secretory IgA and IgG coproantibodies against EG were induced in
      mice of group 2. Weight increased in groups 1 and 2 and tended to be increased in
      group 4 versus group 3. Prolactin concentration was similar in all groups;
      cholesterol concentration was decreased in groups 1, 3, and 4, compared with
      group 5. Compared with that in group 5, serum ALP activity decreased in groups 1
      and 4 and was further decreased in group 1, compared with that in groups 2 and 3;
      it was negatively correlated with anti-EG titer. CONCLUSIONS AND CLINICAL
      RELEVANCE: Induction of anti-EG antibodies and administration of EV monoclonal
      antibodies tended to increase short-term weight gain in this murine model of
      fescue toxicosis. However, systemic IgG antibodies against EG or EV antibodies
      were not protective against decreases in serum ALP activity and cholesterol
      concentrations. Clinical significance of decreased ALP activity associated with
      vaccination is unknown, but represents a worsening of a response often associated
      with fescue toxicosis in cattle.

PMID- 9781459
TI  - Sequence and structural analysis of feline interleukin-5 cDNA.
AB  - OBJECTIVE: To clone and characterize the cDNA encoding feline interleukin-5 (IL
      5) cDNA and the 170 basepairs (bp) of the 5' flanking region of the feline IL-5
      gene. SAMPLE POPULATION: Blood mononuclear cells from a healthy cat. PROCEDURES:
      Cells were cultured, stimulated for 48 hours with concanavalin A, and harvested
      for RNA and DNA isolation. Recovered RNA was used in northern blot and reverse
      transcription-polymerase chain reaction analyses. Resulting cDNA was used for
      rapid amplification of 3' cDNA ends, dideoxy chain termination sequencing, and
      primer extension analysis. RESULTS: Full length cDNA was 838 bp, including a 402
      bp open reading frame that encoded a precursor protein of 134 amino acids
      including a putative peptide signal of 19 residues. Homologies of the nucleotide
      and derived protein sequences between feline and human IL-5 cDNA were 72 and 71%,
      respectively. There also was homology between the human and predicted feline
      cytokines at amino acid positions that are critical for IL-5 receptor binding and
      signal transduction. The 5' flanking region of the feline gene was homologous to
      corresponding regions of the human (88%) and murine (72%) genes, and included
      putative transcriptional regulatory elements. CONCLUSIONS AND CLINICAL RELEVANCE:
      Identification of feline IL-5 cDNA is an important step toward a detailed, fully
      comprehensive characterization of the mechanisms that may be operative in the
      pathogenesis of eosinophilic disorders in cats. The striking homology between the
      human and feline IL-5 genes suggests that cats can be used as animal models for
      human diseases characterized by eosinophil infiltration of tissues.

PMID- 9781460
TI  - Effects of the major Pasteurella multocida porin on bovine neutrophils.
AB  - OBJECTIVE: To evaluate in vitro effect of the major fraction of outer membrane
      proteins of Pasteurella multocida with porin-like activities on some biological
      functions of bovine neutrophils. ANIMALS: Neutrophils from 5 adult cattle.
      PROCEDURE: Variations in such biological processes as actin polymerization and
      chemotaxis and evaluation of hydrogen peroxide attributable to variable
      concentrations of P multocida were recorded and compared. Data were obtained,
      using the porin and lipopolysaccharide (LPS) isolated from a strain of P
      multocida cultivated in brain-heart infusion (BHI) broth. Various concentrations
      of porin and LPS were analyzed to evaluate changes in functional activation and
      microbicidal activity of bovine neutrophils. RESULTS: The 37.5-kd major
      polypeptide of the outer membrane of P multocida was isolated. Presence of this
      porin was significantly correlated with variations of some biological functions
      of bovine neutrophils. These immunocompetent cells had a concentration-dependent
      increase in actin polymerization and chemotactic activity. A concentration
      dependent variation in the oxidative burst also was observed. CONCLUSIONS: The
      porins of gram-negative bacteria affect several biological functions of cells
      involved in the immune response as well as in inflammation. Significant
      correlation of results of in vitro experiments also was identified between porin
      and LPS effect. Pretreatment of bovine neutrophils with various concentrations of
      porin always caused a concentration-dependent increase in examined biological
      activities.

PMID- 9781461
TI  - Characterization of a Pasteurella haemolytica A1 mutant deficient in production
      of three membrane lipoproteins.
AB  - OBJECTIVE: To determine whether a Pasteurella haemolytica A1 mutant that is
      unable to produce membrane lipoproteins has reduced susceptibility to complement
      mediated killing, and to characterize the mutant strain. SAMPLE POPULATION: 12
      sera from cattle resistant to P haemolytica challenge exposure after vaccination
      with P haemolytica or its antigens, or after natural exposure. PROCEDURES:
      Complement-mediated killing assays were performed, using wild-type and mutant
      strains and, as antibody source, various immune sera from cattle that were
      resistant to P haemolytica challenge exposure. Antibody response to whole-cell
      antigens produced by mutant and wild-type strains, production of outer membrane
      proteins and iron-regulated outer membrane proteins by the 2 strains, and growth
      of the 2 strains in various media were analyzed. RESULTS: Compared with wild-type
      P haemolytica, the lipoprotein mutant strain had increased susceptibility to
      bovine complement-mediated killing. Aside from the lipoproteins that are not
      produced by the mutant, immunoblot analysis did not reveal differences between
      immunoreactive antigens that are produced by the 2 strains. Some iron-regulated,
      outer membrane proteins, which usually are only produced by P haemolytica under
      iron-deficient conditions, were produced constitutively by the mutant. The mutant
      grew to a lower final cell density and at a lower rate under conditions likely to
      reflect those encountered in vivo. CONCLUSIONS: Lack of 3 membrane lipoproteins
      resulted in enhanced susceptibility to bovine complement-mediated killing. Site
      specific mutagenesis of genes encoding P haemolytica membrane lipoproteins alters
      production of iron-regulated outer membrane proteins by P haemolytica. Growth
      characteristics of the mutant suggested that it may have reduced capacity for
      survival in vivo.

PMID- 9781462
TI  - Immunophenotypic characterization of lymphomas from the mediastinum of young
      ferrets.
AB  - OBJECTIVE: To determine the phenotype of naturally developing lymphomas in young
      ferrets. ANIMALS: 10 ferrets with lymphoma. PROCEDURE: Neoplastic tissues were
      graded histologically according to the National Cancer Institute's Working
      Formulation for non-Hodgkin's lymphoma and phenotype was determined by means of
      immunohistochemical staining. A polyclonal anti-human CD3 and a monoclonal anti
      human CD79 antibody were used to classify the lymphomas in situ as T-cell or B
      cell origin. Specificity of antibodies was determined by evaluating lymphoid
      tissue from normal ferrets in situ, which was confirmed by western blot analyses.
      RESULTS: All 10 ferrets had clinically aggressive tumors, irrespective of the
      phenotype. Nine ferrets had T-cell lymphoma that extensively involved the
      mediastinum. Remnants of thymic tissue, indicative of thymic origin, were
      identified in lymphoma of these 9 ferrets. One ferret had a B-cell multicentric
      lymphoma without involvement of the mediastinum. CONCLUSIONS: The majority of
      lymphomas in these young ferrets involved the mediastinum and were of T-cell
      phenotype. Impact for Human Medicine-There are many similarities between the
      lymphoma syndrome of ferrets and the condition documented for cats and children
      with lymphoma of the mediastinal area. CLINICAL RELEVANCE: Differential diagnoses
      for young ferrets with clinical signs of lethargy or respiratory distress should
      include T-cell lymphoma of the mediastinum.

PMID- 9781463
TI  - Effects of buprenorphine on cardiovascular and pulmonary function in clinically
      normal horses and horses with chronic obstructive pulmonary disease.
AB  - OBJECTIVES: To evaluate the cardiovascular and respiratory effects of
      buprenorphine administered intravenously in clinically normal horses and horses
      with chronic obstructive pulmonary disease (COPD). ANIMALS: 5 clinically normal
      horses and 5 horses with COPD that were in partial clinical remission (period A)
      or were having an acute attack of airway obstruction (period B). PROCEDURES:
      Pulmonary function testing, arterial blood gas analysis, and arterial blood
      pressure measurements were performed before and after a single intravenous bolus
      of buprenorphine (3 microg/kg of body weight). Respiratory rate (f), tidal volume
      (VT), expiratory-to-inspiratory time ratio (TE/TI), minute expiratory ventilation
      (VE), maximal change in transpulmonary pressure (deltaPL), dynamic compliance
      (Cdyn), and pulmonary resistance (RL) were calculated with a pulmonary function
      computer. Heart rate (HR) and systolic (SABP), diastolic (DABP), and mean
      arterial blood pressures (MABP) were measured. RESULTS: At baseline, COPD horses
      in period A had decreased Cdyn and increased f, VE, PL, and HR, whereas COPD
      horses in period B had decreased TE/TI and Cdyn, arterial blood pH, and PO2, and
      increased f, VE, deltaPL, and RL, compared with clinically normal horses. After
      drug administration, SABP, DABP, and MABP increased in all horses, f and VE
      increased in clinically normal horses, and PaO2 decreased within 60 minutes in
      horses with COPD. CONCLUSION AND CLINICAL RELEVANCE: Buprenorphine can induce
      excitement in unsedated horses or horses that do not have signs of pain, but does
      not seem to induce severe respiratory depression or adverse cardiovascular
      effects in clinically normal horses or those with COPD.

PMID- 9781464
TI  - Comparison of two techniques for total intravenous anesthesia in horses.
AB  - OBJECTIVE: To characterize responses associated with two 1-hour total intravenous
      anesthesia techniques in horses. ANIMALS: 6 mature, healthy mares. PROCEDURE:
      Each horse was anesthetized 3 times. Treatment order was determined by a series
      of Latin squares. After baseline measurements and instrumentation, horses were
      given xylazine (XYL) i.v.; anesthesia was induced 5 minutes later with 10%
      guaifenesin given i.v., then either ketamine (KET) or propofol (PRO) was given
      i.v. After anesthesia induction, each horse received an infusion of XYL and
      either KET or a low or high dose of PRO. Cardiopulmonary variables were measured
      at 20, 40, and 60 minutes after the start of the infusion; arterial blood samples
      were collected prior to each set of measurements, and blood gas tensions and
      plasma drug concentration were determined. A noxious stimulus was applied after
      each of the 3 sets of measurements. RESULTS: Differences in measured
      cardiopulmonary variables were significant among all treatments at different
      times. Most notable differences were between KET and high PRO. Times to regaining
      sternal and standing posture were shortest for KET, and differed significantly
      from values for low and high PRO. Purposeful responses were not observed for high
      PRO in horses after noxious stimulation. In contrast, 4 horses given KET
      responded at all time points and 1 horse given low PRO responded. CONCLUSION:
      None of the infusion techniques were flawless, but results support continued
      efforts at technique refinement and selected clinical use.

PMID- 9781465
TI  - Use of the breath hydrogen test to assess the effect of age on orocecal transit
      time and carbohydrate assimilation in cats.
AB  - OBJECTIVE: To evaluate the effect of age on orocecal transit time (OCTT) in cats,
      using the breath hydrogen test, and to assess potential differences in nutrient
      absorption. ANIMALS: 27 healthy cats. PROCEDURE: Cats were allocated to the
      following 3 groups on the basis of age: group A (9 kittens, 5 to 7 months old),
      group B (9 young adults, 3 to 5 years old), and group C (9 older cats, 12 to 15
      years old). Cats were fed a standard canned diet for 2 weeks prior to measurement
      of OCTT. Exhaled hydrogen concentration (parts per minute [ppm x min]) was
      monitored for 8 hours after feeding 60 g of the canned diet. RESULTS: Mean OCTT
      in group-A cats was 203 minutes (range, 90 to 345 minutes), which was
      significantly different from that in group-B (317 minutes; range, 180 to 435
      minutes) and group-C (309 minutes; range, 225 to 375 minutes) cats. Median area
      under the breath hydrogen excretion time curve (ppm x min) for the 8-hour
      monitoring period, first 45 minutes, and 105 minutes after OCTT for the 3 groups
      was not significantly different among groups. CONCLUSIONS: Kittens had
      significantly faster OCTT than did adult cats.

PMID- 9781466
TI  - Histamine-induced gastric acid secretion in horses.
AB  - OBJECTIVE: To determine gastric secretory responses in horses treated with
      histamine and to determine the dose of histamine needed to elicit maximal gastric
      secretion. ANIMALS: 6 adult horses with an indwelling gastric cannula. PROCEDURE:
      Gastric contents were collected in 15-minute periods, and volume, pH, hydrogen
      ion concentration, hydrogen ion output, sodium concentration, and sodium output
      were determined. Values were determined without any treatment (baseline), after
      administration of pyrilamine maleate (1 mg/kg of body weight, i.v., given during
      a 15-minute period), and during 1-hour infusions of histamine at 3 rates (7.5,
      15, and 30 microg/kg/h, i.v.). RESULTS: Volume and hydrogen ion concentration of
      gastric contents and hydrogen ion output were significantly increased, compared
      with baseline values, during histamine infusion. Mean hydrogen ion concentration
      and hydrogen ion output were significantly greater during infusion of histamine
      at a rate of 15 or 30 microg/kg/h than at a rate of 7.5 microg/kg/h. Sodium
      concentration was significantly decreased, compared with baseline value, during
      histamine infusion, but sodium output was unchanged. CONCLUSIONS: Histamine at
      doses of 15 and 30 microg/kg/h, i.v. stimulated maximal gastric secretion in
      horses. Histamine appeared to induce only parietal secretion. CLINICAL RELEVANCE:
      This study provides additional information related to equine gastric physiology,
      which may benefit further understanding of the pathogenesis of peptic ulcer
      disease.

PMID- 9781467
TI  - Local hemodynamics, permeability, and oxygen metabolism during acute inflammation
      of innervated or denervated isolated equine joints.
AB  - OBJECTIVES: To determine oxygen metabolism, permeability, and blood flow in
      isolated joints in response to interleukin 1beta (IL-1beta) and contribution of
      innervation. SAMPLE POPULATION: One metacarpophalangeal (MCP) joint of 24 adult
      horses. PROCEDURE: The MCP joint was isolated for 6 hours in a pump-perfused,
      auto-oxygenated, innervated or denervated preparation. Isolated joints were
      assigned to the following 4 groups: control, control-denervated, inflamed, and
      inflamed-denervated, and inflammation was induced by intra-articular injection of
      IL-1beta. Circuit arterial and venous pressures, flows, and blood gas tensions,
      synovial fluid production, and intra-articular pressure were measured. Total
      vascular resistance; oxygen delivery, consumption, and extraction ratio (ER); and
      permeability surface area product were calculated. Synovial membrane blood flow
      was determined at 0, 60, and 330 minutes. Synovial membrane wet-to-dry ratio was
      obtained, and permeability to macromolecules was determined by intra-articular
      injection of Evans blue albumin and fluorescein isothiocyanate-conjugated
      dextran. RESULTS: Oxygen delivery and synovial membrane blood flow progressively
      increased but were not different among groups. Oxygen consumption and ER
      significantly increased in inflamed joints, as did intraarticular pressure and
      synovial fluid production. Inflamed joints had greater wet-to-dry ratio. Albumin
      permeability significantly increased in the villous synovial membrane of the
      inflamed groups, and dextran permeability was increased in the innervated groups,
      with a trend toward increased permeability in inflamed groups. CONCLUSION:
      Inflammation significantly increased oxygen demand, which was initially met by
      increased ER. Permeability to small molecules was increased with inflammation;
      innervation increased permeability to large molecules. Use of an isolated joint
      model enabled documentation of the physiologic responses of the joint to acute
      inflammation.

PMID- 9781468
TI  - Cloning and expression of porcine recombinant soluble tumor necrosis factor
      receptor 1.
AB  - OBJECTIVE: To clone, sequence, and express porcine recombinant soluble tumor
      necrosis factor receptor 1 (sTNFR1). PROCEDURE: A polymerase chain reaction (PCR)
      based library enrichment technique was used to isolate a fragment of porcine
      TNFR1. The mature extracellular domain of porcine TNFR1 was subcloned into an
      expression vector and expressed in Escherichia coli as a fusion protein. Protein
      product was purified by immunoaffinity chromatography, using a commercially
      available affinity gel specific for the marker peptide of the fusion protein. The
      bioactivity of the purified protein was tested for its ability to inhibit TNF
      mediated cytotoxicity in a PK(15) bioassay. RESULTS: A 927-base pair fragment of
      porcine TNFR1 encoding the entire extracellular and transmembrane domains, as
      well as 75 amino acids of the cytoplasmic domain, was isolated from a porcine
      lung cDNA library. The extracellular domain was expressed as a soluble TNFR1
      fusion protein with a yield of 120 to 150 microg/L of culture. Affinity-purified
      porcine sTNFR1 was able to inhibit TNF-mediated cytotoxicity of porcine PK(15)
      cells in dose-dependent manner. CONCLUSIONS: Porcine recombinant sTNFR1 inhibits
      TNF bioactivity in vitro. This recombinant protein will be useful for developing
      TNFR1 antibodies and studying the roles of TNF and TNFR1 in the pathogenesis of
      infectious diseases in swine.

PMID- 9781469
TI  - Long-term surgical preparation of portal vein-drained viscera for determination
      of their nutritional requirements in preruminant calves.
AB  - OBJECTIVE: To develop a surgical preparation to study the nutrient concentration
      difference across the portal vein-drained viscera of preruminant calves over a 2
      week period. ANIMALS: 9 healthy preruminant male Holstein calves. PROCEDURE: A
      bilateral subcostal approach was used to reach the portal area to provide access
      for proper placement of an ultrasonic transit time flow probe around the portal
      vein. The umbilical vein was used as an entry point for the portal vein catheter.
      The femoral artery was also catheterized. Calves were observed daily, and food
      intake was recorded. Body weight was recorded weekly. The calves were
      euthanatized, and necropsy was performed 2 weeks after surgery. RESULTS: Of the 9
      calves, 7 recovered without surgical complications. Within 24 hours of surgery, 1
      calf developed an intestinal hernia at the flank incision that was surgically
      repaired without further complications. One calf was euthanatized a week after
      surgery because it developed septicemia secondary to catheter-related infection.
      CONCLUSION: The bilateral subcostal approach provided access to the portal area,
      and the umbilical vein was useful as an entry point. Application of an ultrasonic
      flow probe provided consistent measurements of blood flow over a 2-week period.
      CLINICAL RELEVANCE: These results may have implications for development of
      treatment to promote gastrointestinal tract healing in calves with diarrhea.

PMID- 9781470
TI  - Periodontal healing of canine experimental grade-III furcation defects treated
      with autologous fibrinogen and absorbable barrier membrane.
AB  - OBJECTIVE: To determine the effects of autologous fibrinogen (AF) and absorbable
      barrier membrane (ABM) on periodontal healing of canine experimental grade-III
      furcation defects. ANIMALS: 18 conditioned, laboratory-source, adult Beagles.
      PROCEDURE: Defects were developed bilaterally at the second and fourth premolars
      and maintained for 12 weeks. Defects were treated with AF, ABM, AF and ABM, or
      debridement. Digital subtraction radiography, histologic evaluation, and
      histomorphometric analysis of defect healing was done at 1, 3, and 6 months after
      treatment to determine percentage increases in bone volume, height, area, and
      length of periodontal regeneration along the perimeter of the defect. RESULTS:
      Comparison of defects at post-treatment intervals indicated significantly greater
      healing of debridement and AF-treated defects, compared with ABM-treated defects
      at 3 months; however, by 6 months, there were no significant differences in
      defect healing for all histomorphometric variables. Defects treated with ABM were
      associated with significantly less root ankylosis than other treatments. Defects
      treated with debridement had significantly greater increases in bone volume at 6
      months after treatment, compared with groups treated with ABM. There was a
      significant correlation between regenerated bone area, bone volume, and
      periodontal regeneration for all treatments at 3 and 6 months after treatment.
      CONCLUSION AND CLINICAL RELEVANCE: Use of AF and ABM did not enhance the amount
      of periodontal healing, compared with debridement only. The ABM-treated defects
      were essentially devoid of root ankylosis. Grade-III furcation defects may
      respond equally well to conservative periodontal surgery or guided tissue
      regenerative techniques. The prevention of root ankylosis is a substantial
      benefit favoring this latter method of treatment.

PMID- 9781471
TI  - Experimental implantation of posterior chamber prototype intraocular lenses for
      the feline eye.
AB  - OBJECTIVE: To measure postoperative anterior chamber depth (ACD), corneal
      curvature, and refractive state of feline eyes after lens removal and
      implantation of a prosthetic intraocular lens (IOL) and determine appropriate IOL
      use in cats. ANIMALS: 8 clinically normal adult cats. PROCEDURE: A-scan
      ultrasonic biometry, keratometry, and streak retinoscopy were performed on both
      eyes of each cat before and after lens removal and implantation of a prosthetic
      IOL. Three diopter (D) IOL strengths were used: 48, 51, and 60 D. Measurements
      were recorded for 12 weeks after surgery. RESULTS: IOL were well tolerated by
      cats, with no serious complications attributable to implantation or presence of
      the IOL. The ACD was significantly greater after (8.30 mm) than before (4.97 mm)
      surgery; however, it became slightly more shallow during the 4 weeks after
      surgery, suggesting that the IOL shifted anteriorly in the eye. Significant
      difference in corneal curvature was not detected before or after surgery among
      eyes with various IOL. Twelve weeks after surgery, eyes with 48-, 51-, and 60-D
      IOL had mean +/- SD refractive state of +2.1 +/- 0.49, +0.42 +/- 0.20, and -2.6
      +/- 0.78 D, respectively. Linear regression analysis of refractive state on IOL
      power for all eyes at 12 weeks after surgery predicted that +52.8-D IOL was
      necessary to best approximate emmetropia in these cats. CONCLUSION AND CLINICAL
      RELEVANCE: IOL of substantially higher diopter strength than that needed in dogs
      was required to achieve emmetropia after lens extraction in cats. A 52- to 53-D
      IOL is required to correct feline eyes to near emmetropia after lens removal.

PMID- 9781472
TI  - Vitamin E (alpha-tocopherol) in the treatment of tardive dyskinesia: a
      statistical meta-analysis.
AB  - Tardive dyskinesia is an involuntary movement disorder developing following
      treatment with neuroleptics. As many as 50% of chronic psychotic patients develop
      this disabling condition. No treatment has been found effective for tardive
      dyskinesia. This study was undertaken to meta-analyze the effects of vitamin E
      (alpha-tocopherol) reported in the last decade. All studies published since 1987,
      focusing on vitamin E and tardive dyskinesia are reviewed. Double-blind studies
      are analyzed using measures of effect and variance as described by secondary
      analysis of magnitude of effects in pooled data. A total of 223 patients received
      vitamin E treatment (400-1600 IU/day) for tardive dyskinesia, in 12 studies. A
      significant subgroup (28.3%) showed a modest improvement. Vitamin E was well
      tolerated, and only rarely did side effects occur-of no clinical significance.
      Vitamin E is a safe, well-tolerated compound that may provide some beneficial
      effects in patients suffering from neuroleptic-induced tardive dyskinesia.

PMID- 9781473
TI  - Atypical antipsychotics as enhancement therapy in rapid cycling mood states: a
      case study.
AB  - Rapid cycling is not an uncommon occurrence in patients with bipolar affective
      disorder. This variant of the disease is notorious for its treatment resistance,
      in particular, lithium resistance. A full spectrum of cycloid mood states has
      been described. The author presents five cases in which the addition of atypical
      antipsychotics resulted in significant symptom relief. An argument for a
      preferential use of atypical antipsychotics, with their low risk of tardive
      dyskinesia, is made. General guidelines for the use of atypical antipsychotics in
      rapid cycling patients are discussed. Atypical antipsychotic medications in
      "cycloid disorders," including rapid cycling bipolar disease, are discussed.

PMID- 9781474
TI  - Olanzapine augmentation of clozapine.
AB  - In clinical practice, patients are encountered who are partial responders or
      nonresponders to clozapine. There are others who are unable to tolerate a high
      dosage of clozapine. In the two cases presented, we propose an alternative
      strategy using olanzapine in combination with clozapine in treatment-refractory
      patients. Olanzapine was found to be helpful in these patients, however,
      controlled studies are needed.

PMID- 9781475
TI  - Psychiatric and neuropsychological abnormalities in Huntington's disease: a case
      study.
AB  - The authors describe an atypical presentation of Huntington's disease in a 55
      year-old woman who manifested essentially psychotic and cognitive symptoms. A
      positive family history of Huntington's disease and DNA analysis helped to
      establish the diagnosis. The patient's psychotic symptoms improved with
      risperidone. The psychiatric and cognitive symptoms of Huntington's disease are
      reviewed.

PMID- 9781476
TI  - Biases associated with genotype and sex in prediction of fat-free lean mass and
      carcass value in hogs.
AB  - Carcass and live measurements of 165 market hogs that represented seven genotypes
      were used to investigate genotype and sex biases associated with the prediction
      of fat-free lean mass (FFLM) and carcass value. Carcass value was determined as
      the sum of the product of weight of individual cuts and their average unit prices
      adjusted for slaughter and processing costs. Independent variables used in the
      prediction equations included carcass measurements, such as optical probe,
      midline ruler, ribbed carcass measurements, and electromagnetic scanning
      (EMSCAN), and live animal ultrasonic scanning. The effect of including
      subpopulation mean values of independent variables in the prediction equations
      for FFLM and carcass value was also investigated. Genotype and sex biases were
      found in equations in which midline backfat, ribbed carcass, EMSCAN, and live
      ultrasonic scanning were used as single technology sets of measurements. The
      prediction equations generally undervalued genotypes with above-average carcass
      value. Biases were reduced when measurements of combined technologies and mean
      adjusted variables were used. The FFLM and carcass value of gilts were
      underestimated, and they were overestimated of barrows. Equations that combined
      OP and EMSCAN technologies were the most accurate and least biased for both FFLM
      and carcass value. Equations that included carcass weight and midline last-rib
      backfat thickness measurements were the least accurate and most biased. Genotype
      and sex biases must be considered when predicting FFLM and carcass value.

PMID- 9781477
TI  - Ultrasonic evaluation for the time of ovulation in ewes treated with norgestomet
      and norgestomet followed by pregnant mare's serum gonadotropin.
AB  - Progestogens and follicular stimulants have proved reasonably successful for
      estrus synchronization, but time of ovulation relative to removal of the
      progestogen is not clearly established. We monitored time of ovulation in ewes
      following synchronized estrus. Ovaries of 40 Dorset and Rambouillet x Dorset ewes
      were evaluated during the spring and fall (20/replicate). Ewes were randomly
      assigned to one of two treatment groups (n = 20/group): implant-only (I) ewes
      received a norgestomet implant for 10 d; and implant + PMSG (PI) ewes received a
      norgestomet implant for 10 d with an i.m. injection of 500 IU of PMSG at implant
      removal. Time of estrus onset was detected with the HeatWatch Estrus Detection
      System. Following the initiation of estrus, ovaries were monitored via rectal
      ultrasonography every 6 h to determine the interval from implant removal to
      ovulation (OVUL), and onset of estrus to ovulation (INT). Four I and PI ewes that
      lost implants before scheduled removal on d 10 were removed from the study.
      Estrus was detected in 13 of 16 (81%) I and 14 of 16 (88%) PI ewes within 108 h
      after implant removal. The interval from implant removal to estrus (EST), INT,
      and OVUL were not affected by replicate. The INT was not different in I (33.8 h)
      and PI (35.0 h) ewes. Mean OVUL was greater (P < .01) in I (79.8 h) than in PI
      ewes (68.6 h), and mean EST was also greater (P < .01) for I (46.0 h) than for PI
      ewes (32.6 h). The present data indicate that ovulation occurs on average 70 to
      80 h after implant removal in ewes treated with norgestomet, and PMSG reduces the
      interval from implant removal to ovulation.

PMID- 9781478
TI  - Influence of tempering on the feeding value of rolled corn in finishing diets for
      feedlot cattle.
AB  - Crossbred yearling steers (n = 125; 372 kg) were used in a 109-d finishing trial.
      Steers were fed an 88% concentrate diet containing 65% corn (DM basis) as 1) dry
      rolled corn (DRC); 2) tempered rolled corn (TRC), 43 mg surfactant (SarTemp)/kg
      corn; 3) TRC, 172 mg surfactant/kg corn; 4) TRC, 430 mg surfactant/kg corn; and
      5) steam-flaked corn (SFC). Corn moisture was greater (3.5%, P < .01) for TRC
      than for DRC but less (10%, P < .05) than for SFC. Starch enzymatic reactivity
      was less for TRC than for either DRC (18%, P < .05) or SFC (42%, P < .01).
      Tempering increased the integrity of rolled corn and reduced the amount of
      particles less than 2 mm in diameter by 54% (P < .01). Steam flaking corn
      increased (P < .01) proportion (78%) of the grain having a particle size
      distribution of greater than 8 mm, as compared with TRC (25%) and DRC (3%).
      Compared with DRC, tempering enhanced (P < .10) ADG (9%), feed efficiency (5%),
      and dietary NE (3%). Daily weight gain was similar (P > .10) for TRC and SFC.
      Feed efficiency (P < .10) and dietary NE (P < .01) were greater (6%) for SFC than
      for TRC. There were no differences (P > .10) between DRC and TRC in ruminal and
      total tract digestion of OM, N, and starch, and in ruminal microbial efficiency.
      Ruminal digestion of OM decreased (linear effect, P < .05) and ruminal microbial
      efficiency increased (linear effect, P < .05) with increasing surfactant
      concentration. Ruminal digestion of OM and starch, and flow of nonammonia N to
      the small intestine were greater (31, 56, and 14%, respectively, P < .01) for SFC
      than for TRC. Postruminal and total tract digestion of OM, N, and starch, and
      dietary DE were greater (P < .01) for SFC than for TRC. We concluded that
      tempering corn will enhance animal performance. Increasing the concentration of
      surfactant used in tempering may enhance ruminal microbial efficiency and lean
      tissue growth.

PMID- 9781479
TI  - Identification of quantitative trait loci affecting carcass composition in swine:
      I. Fat deposition traits.
AB  - One of the major determining factors in the price of market hogs today is backfat
      depth. Therefore, identification of regions of the genome affecting this trait
      could be very useful to the swine industry. A large resource population (n = 540)
      was developed by backcrossing F1 Meishan-White composite females to either
      Meishan or White composite boars. A genomic scan was conducted by genotyping all
      animals with microsatellite markers spaced at approximately 20-cM intervals
      across the entire porcine genome. Breed of origin for all chromosomal segments
      was determined using multipoint linkage procedures, and a least squares
      regression analysis was conducted. Nominal P-values were converted to a genome
      wide level of significance to adjust for the numerous tests conducted. Traits
      analyzed were backfat depths at the first rib (FRIB); 10th rib (10th); last rib
      (LRIB); last lumbar (LLUM) vertebra; the average of FRIB, LRIB, and LLUM (AVBF);
      and weight of leaf fat (LEAF). Significant quantitative trait loci (QTL) were
      detected on chromosomes 1, 7, and X. Suggestive evidence for QTL was present on
      chromosomes 5, 8, 9, 10, 13, and 14. Genotypic means for the loci detected
      indicated a predominantly additive mode of inheritance. Meishan alleles produced
      fatter pigs for all loci except those on chromosomes 7 and 10. Additional
      research should be conducted to refine the estimated position of each QTL and its
      effect and determine epistatic interactions. These loci should be evaluated in
      other germplasms to determine whether allelic variation at the QTL exists in
      other breeds.

PMID- 9781480
TI  - Identification of quantitative trait loci affecting carcass composition in swine:
      II. Muscling and wholesale product yield traits.
AB  - A genomic scan was conducted on 540 reciprocal backcross Meishan x White
      composite pigs for hot carcass weight (HCWT); loin eye area (LOIN); carcass
      length (CRCL); belly weight (BELLY); and weight of trimmed ham, loin, picnic, and
      Boston butt adjusted to a constant live (TWPLWT) or carcass (TWPCWT) weight.
      Genetic markers spanned the entire porcine linkage map and were spaced at
      approximately 20-cM intervals. Grandparental breed of origin for all chromosomal
      segments was determined using multipoint linkage procedures, and a least squares
      regression analysis was conducted. Nominal P-values were converted to a genome
      wide level of significance to adjust for the number of tests actually conducted.
      Seven associations were significant at the genome-wide level relating to
      chromosomes 1 (SSC 1), 7 (SSC 7), and X (SSC X). The SSC 1 region affected LOIN,
      TWPLWT, and TWPCWT; SSC 7 affected HWCT and CRCL; and SSC X affected TWPLWT and
      TWPCWT. Twelve associations relating to seven chromosomal regions (including SSC
      1 and X) presented suggestive evidence for quantitative trait loci (QTL), and
      many of these regions are likely to contain QTL. Chromosomes 8 and 14 had two and
      three traits with suggestive evidence for QTL, respectively. Many pleiotropic
      effects were detected for regions on SSC 1, 7, 14, and X in this study and a
      companion study looking for fat deposition QTL in the same population. In
      addition, SSC 4 was nearly significant for CRCL in the same region identified as
      affecting backfat in a wild boar x Large White population. These results expand
      our knowledge of the inheritance of quantitative traits and are directly relevant
      to composite populations containing Meishan germplasm.

PMID- 9781481
TI  - A bootstrap approach to confidence regions for genetic parameters from Method R
      estimates.
AB  - Confidence regions (CR) for heritability (h2) and fraction of variance accounted
      for by permanent environmental effects (c2) from Method R estimates were obtained
      from simulated data using a univariate, repeated measures, full animal model,
      with 50% subsampling. Bootstrapping techniques were explored to assess the
      optimum number of subsamples needed to compute Method R estimates of h2 and c2
      with properties similar to those of exact estimators. One thousand estimates of
      each parameter set were used to obtain 90, 95, and 99% CR in four data sets
      including 2,500 animals with four measurements each. Two approaches were explored
      to assess CR accuracy: a parametric approach assuming bivariate normality of h2
      and c2 and a nonparametric approach based on the sum of squared rank deviations.
      Accuracy of CR was assessed by the average loss of confidence (LOSS) by number of
      estimates sampled (NUMEST). For NUMEST = 5, bootstrap estimates of h2 and c2 were
      within 10(-3) of the asymptotic ones. The same degree of convergence in the
      estimates of SE was achieved with NUMEST = 20. Correlation between estimates of
      h2 and c2 ranged from -.83 to -.98. At NUMEST < 10, the nonparametric CR were
      more accurate than parametric CR. However, with the parametric CR, LOSS
      approached zero at rate NUMEST(-1). This rate was an order of magnitude larger
      for the nonparametric CR. These results suggested that when the computational
      burden of estimating genetic parameters limits the number of Method R estimates
      that can be obtained to, say, 10 or 20, reliable CR can still be obtained by
      processing Method R estimates through bootstrapping techniques.

PMID- 9781482
TI  - Genetic parameters for sex-specific traits in beef cattle.
AB  - Data from 3,593 beef heifers and 4,079 of their steer paternal half-sibs were
      used to estimate genetic parameters of and among female growth and reproductive
      traits and male carcass traits. Estimates of heritability for adjusted 205-d
      weight, adjusted 365-d weight, age at puberty, calving rate, and calving
      difficulty measured on females were .16, .38, .47, .19, and .18, respectively;
      estimates for calving rate and calving difficulty were expressed on a normal
      scale. Estimates of heritability for hot carcass weight; retail product
      percentage; fat percentage; bone percentage; rib eye area; kidney, pelvic, and
      heart fat percentage; adjusted fat thickness; marbling score; Warner-Bratzler
      shear force; taste panel tenderness; taste panel juiciness; and taste panel
      flavor that were measured on steers at an average age of 447 d (weaning age =
      185, days on feed = 262) were .50, .66, .58, .54, .61, .48, .66, .71, .26, .31,
      .00, and .04, respectively. Genetic correlations were positive for heifer weights
      with hot carcass weight, fat percentage, rib eye area, adjusted fat thickness,
      marbling score, and Warner-Bratzler shear force, and they were negative with
      retail product percentage and kidney, pelvic, and heart fat percentage of steers.
      Age at puberty was genetically correlated with taste panel tenderness but not
      with other carcass traits. Calving rate had positive genetic correlations with
      fat percentage, rib eye area, adjusted fat thickness, and taste panel flavor, and
      it had negative genetic correlations with retail product percentage; bone
      percentage; and kidney, pelvic, and heart fat percentage. Calving difficulty had
      favorable genetic correlations with hot carcass weight, retail product
      percentage, and measures of carcass tenderness, but it was unfavorably correlated
      with traits that involve carcass fatness. These results indicate that selection
      for some traits expressed in one sex of beef cattle may result in undesirable
      responses in traits expressed in the opposite sex.

PMID- 9781483
TI  - Effect of ignoring random sire and dam effects on estimates and standard errors
      of breed comparisons.
AB  - Data were weights of F1 calves and weaning weights of top-cross progeny from
      sires and maternal grandsires of 13 breeds. Three analyses were performed on each
      trait to obtain estimates and standard errors of breed effects needed to
      calculate across-breed EPD and accuracies. Model (R) for records of F1 progeny
      contained fixed effects for birth year and date of birth, sex, age and breed of
      dam, and breed of sire, and a random residual effect. The second analysis
      included random effects for sires (RS), and the third analysis included random
      effects for sires and dams (RSD). In maternal analysis of top-cross progeny,
      model (Rm) contained fixed effects for cycle of experiment, age of dam, year of
      birth, sex, breeds of maternal grandam and grandsire, and breed of sire, and a
      random residual effect. In addition, the second and third analyses fit random
      effects for maternal grandsires (RSm) and for maternal grandsires and daughters
      of maternal grandsires (RSDm). Estimates of breed of sire effects changed only
      slightly for different models. Total variance increased in RSD and RS relative to
      R. Standard errors of breed of sire comparisons were underestimated with Model R,
      compared to Models RS and RSD. Standard errors of other contrasts were generally
      not affected. Variance components, breed effects, and standard errors followed
      patterns for Rm, RSm, and RSDm similar to those for R, RS, and RSD. Ignoring
      random variation due to sires and dams underestimated standard errors of breed of
      sire comparisons.

PMID- 9781484
TI  - Comparison of sire breed solutions for growth traits adjusted by mean expected
      progeny differences to a 1993 base.
AB  - Records on growth traits were obtained from five Midwestern agricultural
      experiment stations as part of a beef cattle crossbreeding project (NC-196).
      Records on birth weight (BWT, n =3,490), weaning weight (WWT, n = 3,237), and
      yearling weight (YWT, n = 1,372) were analyzed within locations and pooled across
      locations to obtain estimates of breed of sire differences. Solutions for breed
      of sire differences were adjusted to the common base year of 1993. Then, factors
      to use with within-breed expected progeny differences (EPD) to obtain across
      breed EPD were calculated. These factors were compared with factors obtained from
      similar analyses of records from the U. S. Meat Animal Research Center (MARC).
      Progeny of Brahman sires mated to Bos taurus cows were heaviest at birth and
      among the lightest at weaning. Simmental and Gelbvieh sires produced the heaviest
      progeny at weaning. Estimates of heritability pooled across locations were .34,
      .19, and .07 for BWT, WWT, and YWT, respectively. Regression coefficients of
      progeny performance on EPD of sire were 1.25+/-.09, .98+/-.13, and .62+/-.18 for
      BWT, WWT, and YWT, respectively. Rankings of breeds of sire generally did not
      change when adjusted for sire sampling. Rankings were generally similar to those
      previously reported for MARC data, except for Limousin and Charolais sires, which
      ranked lower for BWT and WWT at NC-196 locations than at MARC. Adjustment factors
      used to obtain across-breed EPD were largest for Brahman for BWT and for Gelbvieh
      for WWT. The data for YWT allow only comparison of Angus with Simmental and of
      Gelbvieh with Limousin.

PMID- 9781485
TI  - Livestock improvement: art, science, or industry?
AB  - The shift in perspectives about livestock improvement over a 70-yr period is
      reviewed. The view changes from livestock improvement as an art, through its
      becoming a science, to its application as a technology in industry. The use of
      scientific tools in corporate settings for poultry, dairy, and swine breeding
      usually involves a strong focus on the economics of production, and this focus
      determines that selection indexes should be used. Such focus has seemed to not
      have been present in breeding for the extensively managed species and livestock
      classes but seems needed in order to provide a basis for organization and
      direction of positive contributions of the breeding segment to the production
      segment.

PMID- 9781486
TI  - Defining multiple-trait objectives for sustainable genetic improvement.
AB  - Genetic improvement is inherently a long-term process in which progress in the
      future is built upon improvement in the past. Discounting of future returns is
      often used in deriving economic values of traits under selection, but this gives
      a short-term perspective that is in conflict with the long-term nature of genetic
      improvement. Changes in management, market environment, and genetic potential
      over time can negatively affect the attainment of breeding goals. Nonlinear
      optimization techniques can be used to find optimum economic weights each year
      over any time horizon. Nearly optimal solutions can be found by deriving economic
      weights for a single, specified future date. Uncertainty about future production
      and marketing environments creates risk that might be lessened by maintaining or
      selecting for diverse genetic stocks that could be used in the future. Such
      programs may need to be coordinated internationally because they may be too
      expensive for individual companies to undertake. Consideration of risk and
      careful analyses of future technical and environmental conditions are needed to
      define multiple trait objectives for long-term genetic change.

PMID- 9781487
TI  - Shortcomings of current genetic evaluation systems.
AB  - Genetic evaluation, as the term is used today in the beef cattle and sheep
      industries, refers to the calculation and dissemination of genetic predictions
      for individual traits. If genetic predictions are to be used wisely, however,
      genetic evaluation should be broadened to include multiple-trait selection
      technology, preferably technology that is customized for individual commercial
      and seedstock producers. Most of the recent research in the area of genetic
      prediction/multiple-trait selection has focused on the use of economic selection
      indexes that incorporate genetic predictions produced within breeds. This
      approach is complicated by genotype x genotype, genotype x environment, and more
      complex interactions, and the changing correlations they create. The use of a
      mechanistic technology, bioeconomic simulation, to calculate economic weights can
      avoid some of the problems caused by interactions, but to implement this
      technology, academic animal breeders must accept the mechanistic concept of
      genetic potential and devise ways to translate current within-breed genetic
      predictions to predictions of this new measure. Sire selection by simulation, a
      multiple-trait selection technology described in detail in this article, uses
      bioeconomic simulation in a way that offers advantages over traditional selection
      indexes in terms of both functionality and appeal. For any customized technology
      to be applied on a meaningful scale, research priorities must change, and the
      business relationships between research groups and animal breeding industries
      must be restructured.

PMID- 9781488
TI  - The U.S. National Sheep Improvement Program: across-flock genetic evaluations and
      new trait development.
AB  - The U.S. National Sheep Improvement Program (NSIP) began in 1987 to provide
      within-flock genetic evaluations for the American sheep industry. An evaluation
      of operating procedures and methodology for NSIP began in 1993 and has resulted
      in across-flock, multiple-trait EPD for three breeds: Targhee, Suffolk, and
      Polypay. Traits reported in the across-flock analyses included direct and
      maternal effects on weaning weight in all breeds, postweaning weight at 120 d in
      Suffolk and Polypay and at 365 d in Targhee, greasy fleece weight in Targhee and
      Polypay, and wool fiber diameter in Targhee. Number born per ewe lambing was also
      evaluated in single-trait analyses for all breeds. Genetic parameters were
      derived separately for each breed. Important genetic antagonisms include an
      unfavorable genetic correlation of .51 between fleece weight and fiber diameter
      in Targhee and a genetic correlation of -.55 between direct and maternal effects
      on weaning weight in Polypay. Estimates of genetic trends between 1987 and 1995
      were consistent with perceived breed roles. In Targhee, direct and maternal
      effects on body weights increased, fiber diameter declined, fleece weight was
      maintained, and number born declined. In Suffolk, direct effects on body weight
      increased, but number born and maternal effects on weaning weight did not change.
      In Polypay, number born and maternal contributions to weaning weight increased,
      but direct genetic merit for body weight declined. Prospective enhancements to
      NSIP include methods for genetic evaluation of performance in accelerated lambing
      and of carcass leanness and development of breeding objectives and selection aids
      for various production systems.

PMID- 9781490
TI  - Public land and natural resource issues confronting animal scientists and
      livestock producers.
AB  - Livestock producers using public lands in the West were once concerned primarily
      with efficient systems for livestock production. Historically, this concept began
      in 1934 with the passage of the Taylor Grazing Act. Management activities on
      public lands continued to focus on sustainable livestock production until the
      1970s, when the public began to demand enforcement of the Multiple Use Act and
      the National Environmental Policy Act. During this time, species listing under
      the Endangered Species Act became more active. Unfortunately, so many species are
      listed or are being considered for listing that it becomes impossible to develop
      biological information on causative factors for listing or recovery plans for
      each one. Peer-reviewed science that addresses management needs is often
      unavailable, and articles from the gray literature have been used in management
      plans for both threatened and endangered species and for public land. Personal
      biases of both scientists and land managers can influence the development of land
      management plans, especially in cases in which scientific information is minimal.
      The Land Grant System is well positioned to develop research applicable for
      public lands. Animal scientists need to be involved in interdisciplinary teams.
      Livestock producers need to overcome the stigma that livestock grazing is not a
      sustainable use. Rangeland in poor condition, whether public or private, should
      be improved if livestock managers are to change the public perception that
      grazing degrades rangeland. To accomplish this, education and peer pressure
      should be used. Another approach needed is activism on the part of producers and
      animal scientists. The public is demanding a voice in public land management.
      Working groups seem to be the emerging pathway to cooperatively develop
      management plans.

PMID- 9781489
TI  - The impact of genetic markers on selection.
AB  - Genetic marker technologies, such as marker-assisted selection, parentage
      identification, and gene introgression can be applied to livestock selection
      programs. Highly saturated genetic maps are now available for cattle, swine, and
      sheep to provide the genetic framework for developing MAS programs. These
      programs rely on three phases for commercialization of the technology: the
      detection phase, in which quantitative trait loci are located and their effects
      on the phenotype measured; the evaluation phase, in which the markers are
      evaluated in commercial populations; and the implementation phase, in which
      markers are combined with phenotypic and pedigree information in genetic
      evaluation for predicting the genetic merit of individuals within the population.
      Predicting the economic impact of genetic technologies is a complex process that
      requires quantitative prediction and economic analysis. Evaluating the impact of
      these benefits across an industry can be achieved through a process in which
      gains from implementation of a genetic technology are assessed at the individual,
      enterprise, and industry levels. A pattern of annual benefits and costs can be
      predicted using gene flows that can be evaluated by conventional economic
      analysis.

PMID- 9781491
TI  - Effects of Synovex-S and recombinant bovine growth hormone (Somavubove) on growth
      responses of steers: III. Muscle growth and protein responses.
AB  - We conducted this study to determine whether the growth responses of specific
      skeletal muscles in crossbred beef steers were differentially affected by
      treatment with recombinant bovine growth hormone (Somavubove, SbV, .1 mg/kg BW,
      i.m., daily), Synovex-S (200 mg progesterone + 20 mg 17-beta estradiol benzoate,
      SYN, ear implant), or a combination of the two. Starting body weights of steers
      averaged 182+/-1.8 kg. Five steers were used at this average BW to obtain data on
      weight and composition of individual muscles at d 0, and 20 other steers were
      assigned in equal numbers to control (C, no implant and placebo daily injection),
      SYN, SbV, and SYN + SbV treatment groups. After 56 d of treatment with placebo or
      growth promoters, complete rectus femoris (RF), triceps brachii (TB),
      supraspinatus (SS), psoas major (PM), and semitendinosus (ST) muscles were
      dissected, weighed, and then ground for determination of moisture, total protein,
      and fat. To calculate the average daily muscle wet weight, protein, and fat
      gains, the initial weight, protein content, and fat content of a muscle were
      subtracted from those obtained at slaughter and the difference divided by 56.
      Muscle weight was increased over C in TB and SS by SYN (P < .1); in TB by SbV (P
      < .09); and in RF (P < .05), TB (P < .03), and SS (P < .03) by SYN + SbV. Overall
      average daily wet tissue gain was increased over C by SbV + SYN (P < .05) in RF,
      TB, and SS. Average daily protein gain in RF and TB was increased by SYN (P <
      .1), SbV (P < .06), and SYN + SbV (P < .01) over that calculated for C. For RF,
      TB, and SS, average daily protein gain was greater (P < . 1) in SbV + SYN than
      that obtained with SbV or SYN alone. These data suggest that administration of
      growth promoters, such as somatotropin and Synovex, to cattle differentially
      affects growth characteristics in certain muscles and can have additive effects
      on protein gain when used together.

PMID- 9781492
TI  - Effects of birth weight and postnatal nutrition on neonatal sheep: I. Body growth
      and composition, and some aspects of energetic efficiency.
AB  - We investigated the effects of birth weight and postnatal nutrition on growth
      characteristics of neonatal lambs. Low- and high-birth-weight male lambs were
      individually reared on a high-quality liquid diet to grow rapidly (ad libitum
      access to feed) or slowly (ADG 150 g) to various weights up to 20 kg live weight
      (LW). Average daily gain tended to be greater in the high- (mean+/-SE 345+/-14 g)
      than in the low- (329+/-15 g) birth-weight lambs given ad libitum access to feed
      owing to slower growth by the small newborns during the immediate postpartum
      period. At birth, on a weight-specific basis, small newborns contained 6.4% less
      nitrogen and tended to have more ash (8.9%) than the high-birth-weight newborns.
      Daily rates of fat, ash, and GE accretion were greater, and nitrogen accretion
      tended to be greater in the rapidly grown large newborns than in their small
      counterparts. At any given empty body weight (EBW) during rearing, low-birth
      weight lambs contained more fat and less ash, resulting in slowly and rapidly
      grown small newborns containing 39.3 and 42.7 Mcal GE, respectively, at
      completion of the study (17.5 kg EBW), compared with 34.8 and 40.5 Mcal in their
      large counterparts. The differences in fatness and energy content between the
      birth weight categories are attributed to energy requirements for maintenance
      that were approximately 30% lower, coupled with higher relative intakes in the
      low-birthweight lambs, during the early postnatal period. At this time, the
      ability to consume nutrients in excess of lean tissue growth requirements was
      apparently more pronounced in small than in large newborns, which resulted in
      lower efficiency of energy utilization for tissue deposition. Furthermore, body
      composition differences between the slowly and rapidly reared lambs support the
      notion of a priority of lean tissue over fat when nutrient supply is limited.

PMID- 9781493
TI  - Growth, body composition, and endocrine responses to chronic administration of
      insulin-like growth factor I and(or) porcine growth hormone in pigs.
AB  - The actions of IGF-I, alone and in combination with porcine growth hormone (pGH),
      on growth and circulating endocrines and metabolites important in growth were
      investigated in peripubertal-age Meishan barrows. Pigs were assigned to four
      treatments: control, buffer; IGF-I, 33 microg rhIGF-I/kg BW injected twice daily;
      pGH, 33 microg rpGH/kg BW injected once daily; and IGF-I+pGH, 33 microg rhIGF
      I/kg BW injected twice daily plus 33 microg rpGH/kg BW injected once daily.
      Treatments were administered for 28 d. Feed intake, BW, and backfat were recorded
      and blood samples were collected weekly. At slaughter, organ and primal cut
      weights were recorded. Offal and half the carcass were ground for chemical
      analysis. Serum concentrations of IGF-I on d 7, 14, 21, and 28 in the IGF-I, pGH,
      and IGF-I+pGH groups were increased 60, 107, and 131%, respectively, compared
      with those of the control group. Administration of pGH increased gain 43%, feed
      efficiency 60%, carcass protein accretion 88%, and trimmed lean cuts 16%, whereas
      IGF-I administration increased gain 22%, carcass protein accretion 33%, and
      trimmed lean cuts 5%. There was little difference in responses to administration
      of IGF-I+pGH and pGH alone except that coadministration of IGF-I with pGH reduced
      the ability of pGH to suppress backfat gain (P < .02). Even though administration
      of IGF-I resulted in a 60% increase in chronic nadir serum concentrations of IGF
      I, only a few growth and carcass measures were changed when compared with control
      pigs. These included increased (P < .05) weight of body, leaf fat, kidneys, and
      belly. The actions of pGH on growth of pigs were not mimicked, and some were
      countermanded by administration of IGF-I at a dose that produces significantly
      increased serum concentrations of IGF-I.

PMID- 9781494
TI  - Beta-adrenergic receptor gene expression in bovine skeletal muscle cells in
      culture.
AB  - Beta-adrenergic receptors (betaAR) are abundant in fetal, neonatal, and adult
      skeletal muscles of cattle; however, only minimal levels of functional betaAR
      were detected in multinucleated muscle cell cultures prepared from 90- to 150-d
      fetal bovine skeletal muscle. Two other lines of evidence were consistent with
      low levels of betaAR expression in bovine muscle cultures. First, treating the
      cells with 10(-6)M isoproterenol for up to 20 min did not increase intracellular
      cAMP concentration. Second, neither the quantity of myosin heavy chain (MHC) nor
      its apparent synthesis rate were changed by treating the cells for 4 d with 10(
      7) or 10(-6) M isoproterenol. Despite these results, the mRNA for the beta2AR
      could be detected in muscle cultures by PCR and on slot blots. Thus, the beta2AR
      mRNA was expressed, but significant levels of functional receptors could not be
      detected. Glucocorticoids are known to activate expression of OAR genes in
      several tissues, and the effect of dexamethasone on OAR gene expression in bovine
      multinucleated muscle cell cultures was evaluated. The intracellular
      concentration of cAMP following treatment with isoproterenol was elevated 10-fold
      by dexamethasone, and the population of functional receptors was elevated by
      approximately 50%. The effect of dexamethasone on muscle protein synthesis and
      accumulation was analyzed after pretreating the cells with dexamethasone for 24
      h, followed by treatment with dexamethasone and 10(-6)M isoproterenol for an
      additional 48 h. The quantity of MHC synthesized and the apparent synthesis rate
      of MHC were stimulated by 10 to 35%. These effects seem to be due to
      posttranscriptional events, because the quantity of beta2AR receptor mRNA on slot
      blots was not increased by treatment with dexamethasone. Results of this study
      emphasize the importance of verifying that muscle cells contain functional betaAR
      when they are used to study the effects of betaAR agonists on muscle protein
      metabolism.

PMID- 9781495
TI  - Body composition analysis of small pigs by dual-energy x-ray absorptiometry.
AB  - We evaluated the use of dual-energy x-ray absorptiometry (DXA) for measuring the
      gross body composition of small subjects in 97 pigs that ranged from 5 to 27 kg
      live body weight. Scans were performed using a Lunar DPXL densitometer in the
      pediatric mode (Version 3.8e). The DXA scans of the live pigs provided
      measurements of total fat, lean, and bone mineral content. After scanning, the
      pigs were killed, the entire body was ground, and samples were analyzed
      chemically (CHEM) for fat, protein, ash, and water content. We found that DXA
      significantly underestimated the percentage of fat in the body (DXA, 6.9+/-.33%
      vs CHEM, 10.9+/-.31%, P < .001). The correlation (r) between DXA and chemical
      measures of percentage fat was .86 and for grams of fat it was .96. Lean tissue
      mass measured by DXA was highly correlated with CHEM measurements of total grams
      of body water (r = .99), total grams of body protein (r = .94), and lean body
      mass (r = .99). The average DXA bone mineral content was within 2% of the amount
      estimated from total body ash and the correlation between the two values was .94.
      The relationships between DXA and CHEM measurements for percentages of body
      composition of pigs that weighed between 5 and 27 kg are described by the
      following regression equations: %fatCHEM = 5.22 + [.817.fatDXA], (r = .86,
      standard error of the estimate, SEE = 1.56); %proteinCHEM = -7.8 +
      [.256%leanDXA], (r = .35, SEE = 2.3); %waterCHEM = -5.2 + [.808-%leanDXA], (r =
      .59, SEE = 3.67). These results are consistent with previously reported results
      and suggest that even though direct use of DXA readings may not be sufficiently
      accurate, the high degree of correlation indicates that with proper calibration
      the DXA values can be used to predict body composition.

PMID- 9781496
TI  - Pork carcass composition: I. Interrelationships of compositional end points.
AB  - Thirty pork carcasses were used to evaluate the interrelationships between
      compositional end points and the accuracy of predicting various end points from
      one another. Right sides were fabricated into Boston butt, picnic, anterior
      belly, posterior belly, anterior loin, posterior loin, and ham. Carcass
      composition was determined on the right side using physical dissection and
      chemical analyses of soft tissue. Left sides were ground (whole-side grind).
      Linear measures and chemical composition were made on left sides. Using
      dissectable components, high (r > .85) correlations occurred between percentage
      of fat-free lean and percentage of lipid, percentage of dissectable fat, and
      lipid in the whole-side grind; between weights of dissectable lean and fat-free
      lean; and between weights of lipid in the whole-side grind and lipid, dissectable
      fat, and dissectible lean. Dissectable lean percentage and fat (percentage and
      weight) could be predicted using weight of lipid, weight of fat-free lean, and
      side weight. Any physical measure could be accurately estimated from any
      compositional end point (r2 = .79 to .93). Regression equations using 10th-rib
      linear measures and hot carcass weights predicted compositional end points with
      R2 > or = .80, with the exception of dissectable lean (R2 = .56).

PMID- 9781497
TI  - Pork carcass composition: II. Use of indicator cuts for predicting carcass
      composition.
AB  - Right sides of 30 pork carcasses were fabricated into indicator cuts (Boston
      butt, picnic, anterior belly, posterior belly, anterior loin, posterior loin, and
      ham) and used to determine carcass composition by physical dissection and
      chemical analysis of soft tissue. Linear measures and chemical composition of
      whole-side grind were collected from left sides. Dissection of indicator cuts to
      predict dissectable composition of the side were much better indicators than
      linear measures (R2 = .70 to .94). Chemical analyses of soft tissue (lean +
      lipid) from the loin and anterior belly were better predictors of fat-free lean
      and extractable lipid composition of the side than linear measures; 89% of the
      variation in dissectable lean of the side was explained by the use of dissectable
      components of the anterior loin. The loin served as the best overall indicator
      cut across the various end points evaluated; 92% of the variation in dissectable
      lean of the side was explained using dissectable components of the shoulder. The
      anterior belly was a good indicator for percentage of dissectable lean, fat, fat
      free lean, and extractable lipid.

PMID- 9781498
TI  - Changes in the calpains and calpastatin during postmortem storage of bovine
      muscle.
AB  - Changes in activity and protein status of micro-calpain, m-calpain, and
      calpastatin in bovine semimembranosus muscle during the first 7d of postmortem
      storage were monitored by using assays of proteolytic activity, SDS
      polyacrylamide gel electrophoresis, and Western blot analysis. Extractable m
      calpain activity changed slightly during the first 7d after death (decreased to
      63% of at-death activity after 7d), whereas extractable calpastatin activity
      decreased substantially (to 60% of at-death activity after 1d and to 30% of at
      death activity after 7d of postmortem storage) during this period. Extractable
      micro-calpain activity also decreased rapidly (to 20% of at-death activity at 1d
      and to less than 4% of its at-death activity at 7d after death) during postmortem
      storage. Western blot analysis showed that the 80-kDa subunit of m-calpain
      remained undegraded during the first 7d after death but that the 125- to 130-kDa
      calpastatin polypeptide was gone entirely at 7d after death. Hence, the
      calpastatin activity remaining at 7d originates from calpastatin polypeptides
      that are 42 kDa or smaller. The 80-kDa micro-calpain subunit was almost entirely
      in the 76-kDa autolyzed form at 7d after death; this form is proteolytically
      active in in vitro systems, and it is unclear why the postmortem, autolyzed micro
      calpain is not active. Over 50% of total muscle micro-calpain is tightly bound to
      myofibrils 7d after death; this micro-calpain is also nearly inactive
      proteolytically. Unless postmortem muscle contains some factor that enables micro
      calpain in this muscle to be proteolytically active, it is not clear whether
      micro-calpain could be responsible for any appreciable postmortem myofibrillar
      proteolysis.

PMID- 9781499
TI  - Effects of preslaughter management on the quality of carcasses from porcine
      stress syndrome heterozygous market hogs.
AB  - The objectives of this study were to determine whether two preslaughter
      management treatments, rest and mixing, influence the muscle quality of porcine
      stress syndrome (PSS) heterozygous (Nn) market hogs and to verify the expected
      quality characteristics of carcasses produced from PSS-normal (NN) and PSS
      susceptible (nn) animals. Twenty-nine Nn, 14 NN, and 9 nn market hogs were
      randomly assigned to preslaughter handling treatments. One-half of the animals in
      each genotype group received 16 h of rest before slaughter, and the remaining
      pigs were slaughtered immediately upon arrival at the Iowa State University Meat
      Laboratory. Within each group, half of the Nn animals were mixed with unfamiliar
      pigs during transport and lairage. Length, backfat, and loin muscle area (LMA)
      were not affected by mixing and rest treatment. The carcasses from nn pigs had
      less fat (P < .05) measured at the 10th rib (off midline) and last lumbar
      vertebra (midline) and possessed larger LMA than carcasses from NN pigs.
      Heterozygous pigs were intermediate for most carcass traits. Carcass pH values
      among heterozygous groups were not significantly different, except that the
      rested animals had higher ultimate pH values (P < .01) and higher 45-min pH
      values. Resting had no effect on pH of NN or nn pigs. The 45-min pH values of nn
      carcasses were lower (P < .01) than those of NN carcasses, but ultimate pH values
      were similar. Values of unrested Nn animals were between those of NN and nn
      genotypes but with rest approached values of NN pigs. Loin muscle Minolta-Y and
      Hunter-L values from unrested Nn animals were higher ( P < .05) than those of
      rested Nn animals. Mixing did not influence these traits. The longissimus muscle
      lipid content was not influenced by treatment but differed among genotypes (P <
      .01). Glycogen levels of rested Nn animals tended to be lower than those of NN
      animals and approached those of nn pigs. Mixing of Nn animals resulted in higher
      (P < .05) chewiness scores of cooked loin chops. No significant cooking loss or
      InstronTM tenderness differences were observed between the PSS-Nn treatment
      groups. Even though 16 h of rest before slaughter improved the color and water
      holding capacity of Nn pigs, effects were small and were much less than those
      that were due to the PSS gene.

PMID- 9781500
TI  - Interactive effects of betaine, crude protein, and net energy in finishing pigs.
AB  - Two experiments were conducted to determine the effect of betaine on growth and
      carcass characteristics of finishing pigs. In Exp. 1, 32 gilts were fed one of
      two diets: 1) a corn-soybean meal basal (B) diet or 2) B + .125% betaine diet. In
      Exp. 2, 122 gilts were allotted to one of eight dietary treatments in a 2 x 2 x 2
      factorial arrangement with two levels of betaine (0 or .125%), crude protein
      (adequate [ACP] or inadequate [ICP]), and net energy (NE; 0 or 6% added fat). In
      Exp. 1, betaine did not affect (P > .10) growth performance or carcass traits
      other than an increased (P < .05) dressing percentage. In Exp. 2, betaine tended
      to decrease ADFI during the overall experimental period (P = .11). In the late
      finishing period (LF), betaine increased ADG in inadequate CP low-NE diets and
      adequate CP high-NE diets, but decreased ADG in inadequate CP high-NE and
      adequate CP low-NE diets (betaine x CP x NE, P < .04). Betaine increased (P <
      .04) carcass length and decreased (P < .01) color score for pork quality. Other
      carcass measurements were unaffected (P > .10) by betaine. Betaine decreased (P <
      .02) serum urea N (SUN) in fed pigs during the LF period. Betaine decreased
      fasting SUN and albumin in pigs fed the ACP diets, but it increased fasting SUN
      and albumin in pigs fed the ICP diets during the LF period (betaine x CP, P =
      .10). Betaine increased serum total protein in the low-NE diets, but not in the
      high-NE diets (betaine x NE, P < .08). The serum metabolite data suggest that
      betaine may affect protein status of pigs, and these effects may depend on the
      crude protein and energy content of the diet.

PMID- 9781501
TI  - Vaccination against ergot alkaloids and the effect of endophyte-infected fescue
      seed-based diets on rabbits.
AB  - Three sequential experiments were conducted with rabbits to 1) determine the
      effect of endophyte-infected (E+) tall fescue seed on rabbit performance and
      examine the effect of anti-ergot alkaloid immunization on rabbit performance and
      protectiveness against fescue toxicosis, 2) compare immunogens designed to elicit
      systemic anti-ergot alkaloid antibodies, and 3) select a superior adjuvant. In
      Exp. 1, rabbits (n = 6/treatment) fed E+ fescue seed diets (20%, 340 ppb total
      ergot alkaloids) had reduced (P < .05) intake and weight gain compared with
      endophyte-free (E-) controls, whereas apparent diet digestibility was not
      different between E+ and E-. Rabbits immunized against ergot alkaloids (E+ vac)
      with lysergol conjugated to human serum albumin (Ly-HSA) had greater (P < .05)
      intake than E+ rabbits during the wk 1 of a 3-wk dietary challenge. In Exp. 2,
      rabbits (n = 4/treatment) were immunized with Ly-HSA, with H100-B (ergot alkaloid
      hapten, H100-different protein carrier, B conjugate), or combinations of both
      with alum as adjuvant. Greatest (P < .001) anti-ergot alkaloid antibody (Ab)
      titer developed in the group immunized with H100-B. In Exp. 3, rabbits (n =
      4/treatment) were immunized with the immunogen H100-B in conjunction with six
      adjuvants. Freund's incomplete adjuvant (FIA) in combination with DEAE-dextran
      and FIA alone gave highest anti-ergot titers. In summary, rabbit weight gain and
      intake were reduced by feeding E+ fescue seed diets, immunization against ergot
      alkaloids provided temporary improvement in intake, and H100-B conjugate with FIA
      or FIA + DEAE-dextran as adjuvants elicited a superior anti-ergot immune
      response. We believe that rabbits may serve as a model animal for fescue
      toxicosis research.

PMID- 9781502
TI  - Effects of frequency of supplementation on dry matter intake and net portal and
      hepatic flux of nutrients in mature ewes that consume low-quality forage.
AB  - Our objective was to determine the effects of frequency of soybean meal (SBM)
      supplementation on forage intake and net portal-drained viscera (PDV) and hepatic
      flux of nutrients in ewes that consume low-quality forage. Six Polled Dorset ewes
      (BW+/-SD = 82+/-9 kg) fitted with hepatic venous, hepatic portal, abdominal
      aortic, and mesenteric venous catheters were used in a replicated 3 x 3 Latin
      square design. Ewes consumed bromegrass hay (7.5% CP; DM basis). Treatments were
      no supplement (control), SBM fed once every 24 h, or SBM fed once every 72 h. In
      the SBM treatments, SBM was fed to provide 80 g/d of CP. Blood flow and net flux
      measurements were made on the 3rd d of each period so that ewes supplemented
      every 72 h were sampled the day of, the day after, and 2 d after supplementation.
      Arterial concentrations of alpha-amino N (AAN) and ammonia N were lower (P < .01)
      when SBM was fed, whereas arterial concentrations of urea N and oxygen were
      higher (P < .01). Feeding SBM increased net PDV release of AAN and ammonia N, net
      PDV removal of urea N, and oxygen consumption. A SBM x sampling day interaction
      (P < .05) occurred and resulted in greater net PDV absorption of AAN and ammonia
      N on the day after SBM supplementation when ewes were fed SBM on a 72-h interval.
      Net hepatic removal of AAN, ammonia N, and oxygen, and net hepatic release of
      urea N were greater (P < .01) with feeding SBM. The results indicate that the
      interval of SBM supplementation may affect the pattern of absorption without
      affecting the net absorption of nutrients.

PMID- 9781503
TI  - Nutritional evaluation of poultry by-product meal as a protein source for
      ruminants: effects on performance and nutrient flow and disappearance in steers.
AB  - We conducted three studies with steers to evaluate poultry by-product meal (PBM)
      as a supplemental N source for ruminants. An in situ study compared the
      solubility, degradation rate, and ruminal escape of PBM N with blood meal (BM),
      corn gluten meal (CGM), and soybean meal (SBM) N. Additionally, an 84-d growth
      study (n = 95, 228+/-5 kg BW) and a digestion trial (6 x 6 Latin square) were
      conducted. The basal diet for the growth and digestion studies consisted of 49%
      corn silage, 36% cottonseed hulls, and 15% supplement (DM basis). Sources of
      supplemental N (% of total supplemental N) were 100% SBM and 0, 25, 50, 75, and
      100% PBM, with urea used to balance for N. In situ ruminal escape N (25.2, 55.3,
      86.7, and 98.9% for SBM, PBM, CGM, and BM, respectively) was greater (P < .05)
      for PBM than for SBM; however, a greater (P < .05) proportion of BM and CGM N
      escaped ruminal degradation compared with PBM. Dry matter intake, ADG and gain/
      feed increased linearly (P < .003) as PBM increased; however, no differences (P >
      .48) were observed in these variables for 100% PBM compared with 100% SBM.
      Duodenal N flow and small intestinal N disappearance increased linearly (P < .05)
      as PBM increased in the diet. Bacterial N flow to the small intestine was not
      affected (P > .19) by treatment; however, 100% SBM decreased (P < .04) bacterial
      CP synthesis (g bacterial N/kg OM disappearance from the stomach) compared with 0
      and 100% PBM. In vivo ruminal escape N of PBM and SBM was 40.6 and 13.7%,
      respectively. Ruminal NH3 N decreased linearly (P < .001) as PBM increased. These
      data suggest that PBM can replace SBM as a source of supplemental N for steer
      calves that consume a diet based on corn silage and cottonseed hulls.

PMID- 9781504
TI  - Validation of the main modeling methods for the estimation of marker mean
      retention times in the different compartments of the gastrointestinal tract in
      sheep.
AB  - Four Texel wethers (60 to 64 kg) fitted with rumen and duodenal cannulae were
      used to compare methods for estimating mean retention times (MRT) of digesta
      markers. They were fed, in eight equal meals, 1,200 g of a mixture of a chopped
      and ground (8-mm screen) and pelleted orchardgrass hay in the ratios 90/10,
      50/50, 30/70, or 10/90 according to a 4 x 4 Latin square design. Mean retention
      time in the stomach and in the whole tract were estimated by orally delivering
      pulse doses of 170Tm-labeled chopped hay, 169Yb-labeled ground hay, and
      [51Cr]EDTA, followed by duodenal spot-sampling and total collection of feces;
      calculations were done using an algebraic method. Mean retention time in the
      abomasum was estimated following administration of a pulse dose of the markers
      (169Yb-labeled duodenal particles and [51Cr]EDTA) in the abomasum via the ruminal
      cannula through the reticulo-omasal orifice and collecting duodenal samples. The
      reference value for MRT in the reticulorumen (MRTRR) was calculated by
      subtracting MRT in the abomasum from MRT in the stomach. For all markers, fecal
      excretion curves were fitted to a two-compartment age-independent model, a gamma
      2 age dependent-age independent two-compartmental model, and a multicompartmental
      model. Comparisons were made among parameters of the models and their anatomical
      or physiological attributes when these were clearly defined or easily calculated.
      The mean retention time in the reticulorumen (MRTRR) obtained from the
      multicompartment model was similar to those calculated with the algebraic method
      whatever the sampling site and the marker used.

PMID- 9781505
TI  - Antibody to acetylcholine receptor in myasthenia gravis: prevalence, clinical
      correlates, and diagnostic value. 1975.

PMID- 9781506
TI  - Monkey business: CNS infections that will not go away.

PMID- 9781507
TI  - Feeling frontal dysfunction: facilitory paratonia and the regulation of motor
      behavior.

PMID- 9781508
TI  - The role of lamotrigine in the treatment of epilepsy.

PMID- 9781509
TI  - Intravenous phenytoin: cheap but not necessarily a bargain.

PMID- 9781510
TI  - Practice parameter: management issues for women with epilepsy (summary
      statement). Report of the Quality Standards Subcommittee of the American Academy
      of Neurology.

PMID- 9781511
TI  - Management issues for women with epilepsy: a review of the literature.
AB  - OBJECTIVE: A review of literature referable to management issues for women with
      epilepsy (WWE) was undertaken for the development of a practice parameter.
      BACKGROUND: Epilepsy is a common neurologic condition with gender-related
      management implications. Although reviews of this topic often focus on pregnancy
      related issues for WWE, specific health concerns for WWE are present throughout
      all phases of reproductive life. METHODS: An OVID MEDLINE literature search was
      conducted for 1965 to 1997 using the following key words/phrases and cross
      referencing: epilepsy/ seizures and pregnancy, anticonvulsants, antiepileptic
      drugs (AEDs), teratogenesis, oral contraceptives, birth defects, folate/folic
      acid, vitamin K, metabolic bone disease, and breast-feeding. RESULTS: Pregnancy
      outcome literature for WWE spans several decades. Methodology varies and
      interpretation is complicated by modern management strategies. Contributions of
      socioeconomic factors, AEDs, maternal epilepsy, and seizures during pregnancy to
      adverse pregnancy outcomes have not been clearly delineated. There is a biologic
      basis for recommendations concerning contraception, folate supplementation,
      vitamin K use in pregnancy, breast-feeding, metabolic bone disease, catamenial
      epilepsy, and reproductive endocrine disorders, but no outcome studies afford a
      strong evidence base for practice recommendation. CONCLUSIONS: WWE face health
      issues for which there is no available outcome literature to guide decision
      making. The urgent need for studies in many of these areas is highlighted by
      expanded treatment options with new AEDs and epilepsy surgery.

PMID- 9781512
TI  - Mechanisms of clearance of Treponema pallidum from the CSF in a nonhuman primate
      model.
AB  - OBJECTIVES: To establish a model of CNS invasion by Treponema pallidum and to use
      it to investigate the immune mechanisms responsible for clearance. METHODS: Four
      macaques were intrathecally inoculated with 0.6 to 2.1 x 10(8) T. pallidum and
      underwent clinical examinations and blood and CSF collections every 1 to 2 weeks
      for 12 to 13 weeks. The following were determined: serum Venereal Disease
      Research Laboratory (VDRL) and microhemagglutination-T. pallidum reactivities,
      CSF-VDRL, CSF white blood cell (WBC) count, and the presence of viable T.
      pallidum in CSF by the rabbit infectivity test (all animals), as well as the
      presence of T. pallidum in CSF by reverse transcriptase (RT)-PCR, WBC phenotype
      by fluorescence-activated cell sorter, WBC cytokine production by RT-PCR, and
      brain MRI at 10 weeks (two animals). RESULTS: All animals became systemically
      infected and developed CSF pleocytosis that resolved after 8 weeks. CSF T.
      pallidum was detected from 2 to 8 weeks. CSF T lymphocytes were predominantly
      CD4+. Interferon-gamma (IFN-gamma) mRNA was consistently detected in CSF WBCs,
      but interleukin (IL)-4 and IL-5 were not. All animals remained clinically well.
      MRIs were normal. CONCLUSIONS: In this model, T. pallidum is cleared from the CNS
      just as in most humans with early syphilis. Local production of IFN-gamma likely
      participates in this process. This model could be used to clarify the effect of
      retrovirus-induced immunodeficiency on clearance of T. pallidum from the CNS and
      on the local CNS immune response.

PMID- 9781513
TI  - Creutzfeldt-Jakob disease: neurophysiologic visual impairments.
AB  - OBJECTIVE: The predictive value of electrophysiologic visual testing in
      Creutzfeldt-Jakob disease (CJD) was investigated, and the retinal pathologic
      findings in three cases are reported. BACKGROUND: The fatal prognosis of CJD, its
      transmissibility, and the lack of treatment make early diagnosis essential in
      averting human-to-human transmission. Electroretinogram and visual evoked
      potentials have been studied in few cases of CJD. METHODS: A visual
      electrophysiologic examination was performed in 41 consecutive patients referred
      with suspected CJD. The disease had been diagnosed in 24 patients (CJD group; 15
      were confirmed neuropathologically and 9 by clinicolaboratory methods in
      accordance with diagnostic criteria). The remaining 17 patients were diagnosed
      with other neurologic disorders, and served as a control group. RESULTS: Flash
      electroretinogram revealed a significant decrease in the amplitude of the B1 wave
      (<60 microV) and the B/A ratio (<2) in the CJD group compared with those in the
      control group. Flash visual evoked potentials revealed no significant difference
      in latency, but amplitude was increased (>10 microV) in the CJD group, especially
      in patients with myoclonus. CONCLUSIONS: The visual electrophysiologic
      abnormalities provide an interesting noninvasive diagnostic tool in idiopathic
      CJD. The B1-wave decrease is closely correlated with the outer plexiform layer
      abnormalities observed on neuropathologic examination.

PMID- 9781514
TI  - Facilitory paratonia and frontal lobe functioning.
AB  - OBJECTIVE: To learn if paratonia predicts frontal cognitive impairments.
      BACKGROUND: Paratonia, an alteration of tone to passive movement, can be divided
      into oppositional paratonia ("gegenhalten," "paratonic rigidity") and facilitory
      paratonia. Although paratonia has been thought to be induced by frontal lobe
      dysfunction, previous studies suggest that paratonia does not correlate with
      cognitive impairment. However, only oppositional paratonia has been studied in
      this manner, and in these studies only the presence or absence of paratonia was
      assessed instead of a quantitative scale. Facilitory paratonia has not been
      studied for its relation to cognitive function. METHODS: Twenty-five patients
      evaluated for degenerative dementia were assessed on semiquantitative 5-point
      scales for paratonia by two independent raters. A quantifiable test--the modified
      Kral procedure--which assesses continued movement by the patient after cessation
      of passive movement was also administered for comparison with facilitory
      paratonia. To assess frontal lobe function, subjects were tested for echopraxia,
      distractibility, and word fluency. To screen for other cognitive defects,
      subjects were given the Mini-Mental State Examination (MMSE). RESULTS: The
      modified Kral procedure strongly correlated with subjective rating of facilitory
      paratonia. This correlation was significantly stronger than the correlation with
      oppositional paratonia. The modified Kral procedure was also highly predictive of
      echopraxia, but was less predictive of other frontal lobe tests. Facilitory
      paratonia, oppositional paratonia, and the modified Kral procedure each strongly
      predicted scores on the MMSE. CONCLUSIONS: Both facilitory and oppositional
      paratonia strongly predict general cognitive performance. The modified Kral
      procedure is a reliable indicator of facilitory paratonia and a predictor of
      impaired performance on frontal lobe tests.

PMID- 9781515
TI  - Neglect after right hemisphere stroke: a smaller floodlight for distributed
      attention.
AB  - OBJECTIVE: To learn whether there was a defect in an attentional floodlight. We
      used a line decision task for which subjects had to decide if two line segments
      separated by a gap were one line or two parallel lines. We varied the area of the
      gap and, therefore, the area over which subjects needed to spread attention to
      perform the task correctly. BACKGROUND: Visual tasks requiring focused attention
      use an attentional spotlight. Other visual tasks requiring spatially distributed
      attention may require a floodlight. Neglect after right hemisphere stroke can be
      associated with a defect in the attentional spotlight. RESULTS AND CONCLUSIONS:
      Two patients with neglect after right hemisphere stroke performed more poorly
      than normal control subjects and left hemisphere-damaged control subjects as the
      area of spread in the gap increased. Right hemisphere-damaged patients did not
      differ from control subjects' performance on another visuospatial parameter--the
      degree of discontinuity between the line segments. These results support a
      defective attentional floodlight in neglect.

PMID- 9781516
TI  - Emergence of artistic talent in frontotemporal dementia.
AB  - OBJECTIVE: To describe the clinical, neuropsychological, and imaging features of
      five patients with frontotemporal dementia (FTD) who acquired new artistic skills
      in the setting of dementia. BACKGROUND: Creativity in the setting of dementia has
      recently been reported. We describe five patients who became visual artists in
      the setting of FTD. METHODS: Sixty-nine FTD patients were interviewed regarding
      visual abilities. Five became artists in the early stages of FTD. Their history,
      artistic process, neuropsychology, and anatomy are described. RESULTS: On SPECT
      or pathology, four of the five patients had the temporal variant of FTD in which
      anterior temporal lobes are involved but the dorsolateral frontal cortex is
      spared. Visual skills were spared but language and social skills were devastated.
      CONCLUSIONS: Loss of function in the anterior temporal lobes may lead to the
      "facilitation" of artistic skills. Patients with the temporal lobe variant of FTD
      offer a window into creativity.

PMID- 9781517
TI  - Direct genetic evidence for involvement of tau in progressive supranuclear palsy.
      European Study Group on Atypical Parkinsonism Consortium.
AB  - OBJECTIVE: To confirm whether a dinucleotide repeat sequence in an intron of the
      microtubule-associated protein tau is associated with progressive supranuclear
      palsy (PSP) in an independent study population and to establish an improved
      methodology for allelotyping. BACKGROUND: It has recently been reported that a
      genetic variant of tau, known as the A0 allele, was represented excessively in
      PSP patients when compared with control subjects. METHODS: In a multicenter
      study, the authors examined the allelic distribution of this dinucleotide repeat
      marker in a set of clinically ascertained PSP patients (n = 30), multiple system
      atrophy (MSA) patients (n = 35), and matched control subjects (n = 70).
      Individuals were allelotyped using automated analysis of fluorescently labeled
      PCR products. RESULTS: The A0 allele was significantly overrepresented in the PSP
      patients (93.3% versus 76.4%; p = 0.0067; odds ratio [OR] = 4.33; 95% confidence
      interval [CI], 1.36 to 13.60), but not in the MSA patients. Likewise, A0
      homozygotes were overrepresented in the PSP group (86.7% versus 61.1%; p = 0.02;
      OR = 4.14; 95% CI, 1.19 to 14.48) compared with control subjects. CONCLUSIONS:
      The findings of this study, which is the largest to date, support those of a
      previous investigation that used pathologically confirmed PSP patients. These
      data provide additional strong evidence that genetic variation at or near the tau
      gene plays an important role in the pathogenesis of PSP.

PMID- 9781518
TI  - Association of midlife blood pressure to late-life cognitive decline and brain
      morphology.
AB  - OBJECTIVE: To investigate the association between midlife systolic blood pressure
      (SBP) and late-life cognitive decline and brain morphology in a sample of
      community-dwelling elderly men 68 to 79 years of age. METHODS: Subjects are
      surviving members from the prospective National Heart, Lung, and Blood Institute
      Twin Study (intake, 1969 to 1972) who, when examined for a fourth time in 1995
      through 1997, underwent brain MRI and repeated assessment of neurobehavioral
      functioning. Quantification of the MR images determined cerebral volume and total
      volume of white matter hyperintensities (WMHIs) for 392 subjects. Midlife SBP
      levels measured in 1970, 1980, and 1985 were used to classify subjects into low,
      medium, and high midlife SBP categories. A 10-year change in performance on the
      Mini-Mental State Examination, Digit Symbol Substitution Test, Benton Visual
      Retention Test, and Verbal Fluency Test was also calculated for these subjects.
      For all reported analyses, patients were treated as genetically unrelated
      individuals. RESULTS: Subjects with high midlife SBP experienced a greater
      decline in cognitive performance and had larger WMHI volumes at follow-up in late
      life than did those with low midlife SBP. Decreased brain parenchyma and
      increased WMHI volumes were associated with decline in neurobehavioral
      functioning as measured in late life independent of age, education, and baseline
      levels of cognition. CONCLUSIONS: Midlife SBP is a significant predictor of both
      decline in cognitive function and MR volumetric measures of brain atrophy in late
      life. Because decline in neurobehavioral functioning was associated with
      decreased brain volume and increased WMHI volume, we conclude that the long-term
      impact of elevated SBP on decline in late-life neurobehavioral functioning is
      likely to be mediated through its chronic, negative effect on structural
      characteristics of the brain.

PMID- 9781519
TI  - Rate of medial temporal lobe atrophy in typical aging and Alzheimer's disease.
AB  - OBJECTIVES: To determine the annual rates of volumetric change of the hippocampus
      and temporal horn in cognitively normal elderly control subjects and individually
      matched patients with AD, and to test the hypothesis that these rates were
      different. BACKGROUND: Cross-sectional studies consistently reveal cerebral
      atrophy in elderly nondemented subjects compared with healthy young adults, and
      greater atrophy in patients with AD relative to elderly control subjects.
      However, rates of atrophy are estimated most accurately by performing serial
      measurements in the same individuals. METHODS: MRI-based volumetric measurements
      of the hippocampi and temporal horns were performed in 24 cognitively normal
      subjects aged 70 to 89 years who were individually matched with respect to gender
      and age with 24 patients with AD. Each subject underwent an MRI protocol twice,
      separated by 12 months or more. RESULTS: The mean annual rate of hippocampal
      volume loss among control subjects was -1.55+/-1.38% and the temporal horns
      increased in volume by 6.15+/-7.69% per year. These rates were significantly
      greater among AD patients: hippocampus, -3.98+/-1.92% per year, p < 0.001;
      temporal horn, 14.16+/-8.47% per year, p = 0.002. CONCLUSION: A statistically
      significant yearly decline in hippocampal volume and an increase in temporal horn
      volume was identified in elderly control subjects who represent typical aging
      individuals. These rates were approximately 2.5 times greater in patients with AD
      than in individually age- and gender-matched control subjects.

PMID- 9781521
TI  - Brain perfusion imaging predicts survival in Alzheimer's disease.
AB  - BACKGROUND: The variability of disease course in patients diagnosed with AD makes
      prediction of survival difficult, despite the identification of numerous
      predictors to date. This study evaluated the predictive utility of measurements
      of regional cerebral blood flow (rCBF) obtained with SPECT in a group of AD
      patients. METHODS: Fifty AD patients were studied with SPECT and followed
      longitudinally. SPECT measures of relative rCBF were calculated by measuring
      radioactivity densities in dorsolateral frontal, orbitofrontal, temporal, and
      parietal cortex normalized to occipital cortical radioactivity density. Subjects
      were classified into three tertiles of rCBF ratios for each region. These rCBF
      ratios were used as predictors of survival in life-table and proportional hazard
      models to predict survival. RESULTS: Right parietal rCBF was a significant
      predictor of survival in the life-table analysis, with subjects in the lowest
      tertile having shortest survivals. No other brain region was a significant
      predictor of survival. In a proportional hazards model when a variety of other
      potential predictors were accounted for, right parietal rCBF ratio remained a
      significant predictor. CONCLUSIONS: These results demonstrate that brain
      perfusion in the right parietal lobe is a significant predictor of survival in
      patients with AD even when other predictors are taken into consideration. This
      suggests that SPECT perfusion imaging may provide additional useful information
      on disease prognosis in AD.

PMID- 9781520
TI  - Prevalence of Alzheimer's disease and other dementias in rural India: the Indo-US
      study.
AB  - OBJECTIVE: To determine the prevalence of AD and other dementias in a rural
      elderly Hindi-speaking population in Ballabgarh in northern India. DESIGN: The
      authors performed a community survey of a cohort of 5,126 individuals aged 55
      years and older, 73.3% of whom were illiterate. Hindi cognitive and functional
      screening instruments, developed for and validated in this population, were used
      to screen the cohort. A total of 536 subjects (10.5%) who met operational
      criteria for cognitive and functional impairment and a random sample of 270
      unimpaired control subjects (5.3%) underwent standardized clinical assessment for
      dementia using the Diagnostic and Statistical Manual of Mental Disorders-fourth
      edition diagnostic criteria, the Clinical Dementia Rating Scale (CDR), and
      National Institute of Neurological and Communicative Disorders and Stroke
      Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for
      probable and possible AD. RESULTS: We found an overall prevalence rate of 0.84%
      (95% CI, 0.61 to 1.13) for all dementias with a CDR score of at least 0.5 in the
      population aged 55 years and older, and an overall prevalence rate of 1.36% (95%
      CI, 0.96 to 1.88) in the population aged 65 years and older. The overall
      prevalence rate for AD was 0.62% (95% CI, 0.43 to 0.88) in the population aged
      55+ and 1.07% (95% CI, 0.72 to 1.53) in the population aged 65+. Greater age was
      associated significantly with higher prevalence of both AD and all dementias, but
      neither gender nor literacy was associated with prevalence. CONCLUSIONS: In this
      population, the prevalence of AD and other dementias was low, increased with age,
      and was not associated with gender or literacy. Possible explanations include low
      overall life expectancy, short survival with the disease, and low age-specific
      incidence potentially due to differences in the underlying distribution of risk
      and protective factors compared with populations with higher prevalence.

PMID- 9781522
TI  - Oxidative damage to DNA in lymphocytes from AD patients.
AB  - OBJECTIVE: Several studies show structural and functional alterations in
      peripheral cells in AD. The purpose of this study was to evaluate oxidative
      stress in AD lymphocytes. BACKGROUND: The literature supports the role of
      reactive oxygen species in the pathogenesis of AD because several markers of
      oxidative damage have been detected in AD brain. METHODS: 8-hydroxy-2'
      deoxyguanosine (8OHdG), a marker of oxidative stress in DNA, was measured in
      lymphocytes of AD patients and healthy aged controls with high-pressure liquid
      chromatography with electrochemical detection, both at basal condition and after
      acute oxidative stress with hydrogen peroxide. RESULTS: A significantly higher
      concentration of 8OHdG in lymphocytes occurred in AD patients compared with
      controls. In this latter group, 8OHdG increased progressively with age. After
      acute oxidative stress, levels of formed 8OHdG did not differ between AD patients
      and controls. CONCLUSIONS: Our results support that AD is affected by oxidative
      stress, detectable not only in the brain but also in peripheral cells; oxidative
      mechanisms may contribute to the pathogenesis of AD. Additional studies in other
      neurodegenerative diseases are needed to evaluate these findings.

PMID- 9781523
TI  - An active-control trial of lamotrigine monotherapy for partial seizures.
AB  - OBJECTIVE: We report the results of a double-blind, double-dummy, active-control
      study designed to evaluate the efficacy and safety of lamotrigine (LTG)
      administered as monotherapy to adult outpatients with partial seizures.
      BACKGROUND: The effectiveness of LTG as add-on therapy for partial seizures in
      adults has previously been established. METHODS: After an 8-week baseline during
      which patients continued their baseline antiepileptic drug (carbamazepine or
      phenytoin monotherapy), 156 patients were randomly assigned to receive increasing
      doses of LTG (target 250 mg b.i.d.) or valproic acid (VPA; target low dose of 500
      mg b.i.d.) during the first 4 weeks of an 8-week transition period. Carbamazepine
      or phenytoin was withdrawn over the next 4 weeks; then patients entered a 12-week
      monotherapy period. Study drug treatment was discontinued in patients who met
      predetermined escape criteria for seizure worsening. RESULTS: More patients
      receiving LTG were successfully maintained on monotherapy compared with patients
      receiving VPA (56% versus 20%; p < 0.001). The time to meet the escape criteria
      was also significantly longer in LTG-treated patients (median = 168 days) than in
      VPA-treated patients (median = 57 days; p = 0.001). The incidence of adverse
      events during the monotherapy period was lower than during the transition period.
      Four LTG patients and five VPA patients reported serious adverse events. Two of
      those patients experienced a rash that led to withdrawal soon after adding LTG to
      carbamazepine. CONCLUSIONS: We conclude that LTG is effective and well tolerated
      when administered as monotherapy in adult patients with partial seizures.

PMID- 9781524
TI  - Cost-effectiveness model of adjunctive lamotrigine for the treatment of epilepsy.
AB  - OBJECTIVE: To predict the cost-effectiveness of lamotrigine by evaluating the
      costs and health outcomes in treated patients. BACKGROUND: Lamotrigine adjunctive
      therapy has been found to be associated with decreased seizure frequency and
      severity in patients who are refractory to treatment with the older antiepileptic
      drugs (AEDs). METHODS: We used a cost-effectiveness clinical decision analysis
      framework to assess the impact of these clinical benefits on patient health care
      use. The measure of effectiveness was seizure-free days gained. The measures of
      health care resource use included hospitalizations, outpatient and emergency
      department visits, surgery, and AEDs. Medical care use and cost estimates were
      derived from clinical trial data and published sources. Costs and effectiveness
      (incremental costs per seizure-free days gained) of lamotrigine adjunctive
      therapy versus older AEDs were compared in patients refractory to previous
      treatment during three time periods: the start-up year, the second year when
      decisions about surgery were made, and all subsequent years. RESULTS AND
      CONCLUSIONS: The model predicts that use of lamotrigine would be associated with
      an overall reduction in use of other direct medical care resources
      (hospitalizations, outpatient visits, diagnostic and laboratory tests, and
      surgery). For a 10-year time horizon, the estimated cost-effectiveness ratio is
      $6.9 per seizure-free day gained. The model provides a flexible framework to
      analyze the effect of new antiepileptic drugs.

PMID- 9781525
TI  - Incidence and clinical consequence of the purple glove syndrome in patients
      receiving intravenous phenytoin.
AB  - OBJECTIVE: To determine the incidence, risk factors, and long-term sequelae of
      the purple glove syndrome (PGS) in hospital patients receiving IV phenytoin.
      BACKGROUND: PGS is a poorly understood, potentially serious local complication of
      IV phenytoin administration characterized by progressive distal limb edema,
      discoloration, and pain. METHODS: The pharmacologic records of the Mayo
      Foundation hospitals were reviewed to identify 179 consecutive patients who had
      IV phenytoin ordered during a 3-month period. Their hospital records were then
      reviewed to confirm IV phenytoin treatment, the frequency of PGS (defined as the
      progressive development of edema, discoloration, and pain in the limb after
      administration of IV phenytoin), and the outcome of PGS. RESULTS: A total of 152
      patients received IV phenytoin, and nine (5.9%) developed PGS. PGS patients
      received a greater median initial dose of phenytoin, total 24-hour dose, and
      total number of doses (all p < 0.05). In addition, the median age of the PGS
      patients was older, their infusion was more often given for acute seizures, it
      was less likely to be administered in the operating room, and the length of their
      hospital stay was longer (all p < 0.05). One patient required surgical therapy,
      and all other patients resolved within 3 weeks with conservative management.
      CONCLUSIONS: PGS is not rare and elderly patients and individuals receiving
      large, multiple doses are particularly at risk. This iatrogenic complication may
      be preventable by substituting fosphenytoin for IV phenytoin.

PMID- 9781526
TI  - Analysis of prenatal and gestational care given to women with epilepsy.
AB  - OBJECTIVE: To assess past care practices of neurologists and obstetricians to
      identify areas in which practice patterns differ from currently accepted optimal
      care. METHODS: Retrospective chart review of 155 women identified as having a
      diagnosis of epilepsy (or seizure disorder) who had been pregnant any time
      between January 1988 and December 1995 and were admitted to Stanford University
      Hospital for delivery. A total of 161 pregnancies (132 women) were selected for
      study. RESULTS: An obstetrician was seen at some point during the pregnancy in
      99% of the pregnancies, whereas a neurologist was seen at least once in only 64%
      of the pregnancies. In the 3 months before conception, an obstetrician was seen
      in 5% of the pregnancies and a neurologist was seen in 15%. Seventy-five percent
      of the patients taking antiepileptic medication and 65% of the untreated patients
      had documentation of folate supplementation at any time during pregnancy. Vitamin
      K supplementation in the final month of pregnancy was documented for only 41% of
      those receiving antiepileptic drugs. In over one-third of the pregnancies the
      mother did not have a maternal serum alpha-fetoprotein measure documented and a
      similar percentage did not receive genetic counseling. Monitoring of the maternal
      serum concentration of the non-protein-bound fraction of the prescribed
      antiepileptic drugs was not documented. CONCLUSIONS: We identified specific
      omissions of appropriate vitamin supplementation, genetic counseling, and drug
      level monitoring. Educational efforts should be targeted to improve the
      management of pregnancy in women with epilepsy.

PMID- 9781527
TI  - Hypothalamic hamartomas and gelastic epilepsy: a spectroscopic study.
AB  - BACKGROUND: Patients with hypothalamic hamartomas present with epileptic attacks
      of laughter and later experience multiple seizure types and cognitive decline,
      suggestive of secondary generalized epilepsy. It has been suggested in the past
      that gelastic seizures originate in the temporal lobes rather than in the
      hamartoma, but temporal resections have been ineffective. Recent
      electrophysiologic evidence suggests that the epileptogenic discharges may
      originate in the hamartoma itself. METHODS: We used proton magnetic resonance
      spectroscopic imaging to quantify the amount of neuronal damage in the temporal
      lobes and hamartomas of patients with hypothalamic hamartomas and gelastic
      seizures. Five patients were studied and the relative intensity of N
      acetylaspartate to creatine (NAA/Cr) was determined for both temporal lobes as
      well as for the hamartoma. These values were compared with signals from the
      temporal lobes and hypothalami of normal control subjects. RESULTS: NAA/Cr was
      not significantly different from normal control subjects for either temporal
      lobe, nor was there a significant asymmetry between the two temporal lobes for
      any of the patients. NAA resonance signals were present in the hamartomas, and
      the ratio of NAA to Cr was decreased in the hamartomas compared with the
      hypothalami of normal control subjects (t = 4.5, p = 0.005). CONCLUSIONS: We
      found no detectable neuronal damage in the temporal lobes of patients with
      hypothalamic hamartomas and gelastic epilepsy. This is further evidence that
      gelastic seizures do not originate in the temporal lobes of these patients.

PMID- 9781528
TI  - Cerebral hemodynamic changes in sleep apnea syndrome and effect of continuous
      positive airway pressure treatment.
AB  - BACKGROUND AND OBJECTIVE: A clear association among snoring, sleep apnea, and
      increased risk of stroke has been shown by previous studies. However, the
      possible role played by sleep apnea in the pathogenesis of cerebrovascular
      disease is subject to debate. To evaluate the influence of hemodynamic changes
      caused by obstructive sleep apnea syndrome (OSAS), we investigated
      cerebrovascular reactivity to hypercapnia in patients with OSAS. METHODS: The
      study was performed at baseline and after 1 night and 1 month of nasal continuous
      positive airway pressure (n-CPAP) therapy, with patients in the waking state
      (8:00 to 8:30 AM and 5:30 to 6:00 PM) with transcranial Doppler ultrasonography.
      Cerebrovascular reactivity was calculated with the breath-holding index (BHI).
      RESULTS: In the baseline condition, compared with normal subjects, patients with
      OSAS showed significantly lower BHI values in both the morning (0.57 versus 1.40,
      p < 0.0001) and the afternoon (1.0 versus 1.51, p < 0.0001). Cerebrovascular
      reactivity was significantly higher in the afternoon than it was in the morning
      in both patients (p < 0.0001) and controls (p < 0.05). In patients, the BHI
      returned to normal values, comparable with those of control subjects, after both
      1 night and 1 month of n-CPAP therapy. CONCLUSIONS: These findings suggest an
      association between OSAS and diminished cerebral vasodilator reserve. This
      condition may be related to the increased susceptibility to cerebral ischemia in
      patients with OSAS, particularly evident in the early morning.

PMID- 9781529
TI  - A multicenter trial of ropinirole as adjunct treatment for Parkinson's disease.
      Ropinirole Study Group.
AB  - OBJECTIVE: To evaluate the nonergot dopamine agonist ropinirole as an adjunct to
      L-dopa in a randomized, double-blind trial in PD patients with motor
      fluctuations. BACKGROUND: L-dopa in the treatment of PD is associated with motor
      fluctuations, dyskinesia, and other adverse effects. The use of dopamine agonists
      in the treatment of PD delays recourse to L-dopa and thus delays the possibility
      of adverse effect onset. METHODS: Ropinirole (n = 95) or placebo (n = 54) was
      added to L-dopa, and L-dopa was then reduced in a planned manner during the 6
      month trial. RESULTS: A significantly greater number of ropinirole patients were
      able to achieve a 20% or greater reduction in both L-dopa dose and in percent
      time spent "off" compared with placebo (35.0% versus 13.0%; p = 0.003). The mean
      daily L-dopa dose was reduced significantly with ropinirole treatment (242 mg
      versus 51 mg; p < 0.001) as was the percent awake time spent "off" (11.7% versus
      5.1%; p = 0.039). There was no difference in the percent of patients who withdrew
      because of adverse effects (15.8% on ropinirole versus 16.7% on placebo).
      CONCLUSIONS: Ropinirole permits a reduction in L-dopa dose with enhanced clinical
      benefit for PD patients with motor fluctuations.

PMID- 9781530
TI  - Unilateral thalamic deep brain stimulation for refractory essential tremor and
      Parkinson's disease tremor.
AB  - OBJECTIVE: To determine the efficacy and tolerability of unilateral thalamic deep
      brain stimulation (DBS) for patients with medically refractory essential tremor
      (ET) and the tremor associated with Parkinson's disease (PD). BACKGROUND: The
      tremor of ET and PD may produce functional disability despite optimal medical
      therapy. Several reports have demonstrated efficacy of thalamic DBS in this
      scenario. METHODS: Preoperative and 3-month postoperative tremor ratings were
      compared in 33 patients (14 ET and 19 PD) with severe tremor. Evaluations
      included Unified Parkinson's Disease Rating Scale (UPDRS) scores for PD patients
      and a modified Unified Tremor Rating Scale in ET patients. Open-label and blinded
      data (unknown activation status) were obtained. RESULTS: ET patients demonstrated
      an 83% reduction (p < 0.0001) in observed contralateral arm tremor. All measures
      of tremor including writing samples, pouring tests, subjective functional
      surveys, and disability scores improved significantly. PD patients demonstrated
      an 82% reduction (p < 0.0001) in contralateral tremor and significant improvement
      in disability and global impressions. There was, however, no meaningful
      improvement in other motor aspects of the disease, and the total UPDRS part II
      (activities of daily living) score did not change. Adverse events, more common in
      ET patients, were generally mild and were usually eliminated by adjustment of the
      device parameters. CONCLUSIONS: Thalamic DBS is a safe and effective treatment of
      ET and the tremor of PD. In PD, its use should be limited to patients in whom
      high-amplitude tremor results directly in significant functional disability.

PMID- 9781531
TI  - Tourette's syndrome: [I-123]beta-CIT SPECT correlates of vocal tic severity.
AB  - OBJECTIVE: To examine in vivo the density of brain monoaminergic transporters in
      Tourette's syndrome (TS). BACKGROUND: TS is a heritable neuropsychiatric disorder
      characterized by chronic vocal and motor tics and is often associated with
      obsessive-compulsive symptoms. Hyperstimulation of dopamine receptors and
      dysfunction of serotonergic transmission have been implicated in its
      pathogenesis, but direct evidence of involvement of these neurochemical systems
      has been limited. METHODS: Symptom severity and the availability of presynaptic
      monoaminergic transporters in the basal ganglia, midbrain, and thalamus were
      measured using SPECT and the radioligand [I-123]2beta-carbomethoxy-3beta-(4
      iodophenyl)tropane ([I-123]beta-CIT) in 10 patients with TS and in 10 age- and
      sex-matched normal volunteers. RESULTS: A significant negative correlation was
      found between a measure of overall tic severity and beta-CIT binding in the
      midbrain (r = -0.73, p = 0.02) and the thalamus (r = -0.82, p < 0.01). When
      examined post hoc, these correlations were determined largely by vocal tic
      severity. No other significant correlations were found between symptom severity
      and beta-CIT binding in the striatum or cortex. CONCLUSIONS: These findings
      indicate that serotonergic neurotransmission in the midbrain and serotonergic or
      noradrenergic neurotransmission in the thalamus may be important factors in the
      expression of TS and may suggest novel targets for treatment.

PMID- 9781532
TI  - A levodopa kinetic-dynamic study of the rate of progression in Parkinson's
      disease.
AB  - OBJECTIVE: The aims of the study were to follow prospectively the intrasubject
      progression of idiopathic PD in a cohort of patients using levodopa kinetic
      dynamic modeling and to assess the relation between the rate of progression of
      the disease and patients' different clinical characteristics. METHODS: Thirty
      four patients (Hoehn and Yahr stages 1 to 3) enrolled in the longitudinal follow
      up. Each patient was examined at 1-year intervals over a median 4 years by a
      standardized oral levodopa test. The primary measure outcome was the computed
      half-life of levodopa in the "effect compartment" (t1/2eq), a proposed indicator
      of nigrostriatal dopaminergic functionality and integrity. RESULTS: Values of
      levodopa t1/2eq correlated negatively with severity of symptoms (r = -0.652, p <
      0.0001) and decreased over the years together with a worsening of patients'
      clinical stage (p < 0.001). The rate of reduction in drug t1/2eq was more rapid
      in patients at the earlier stages of the disease compared with the more advanced
      ones, falling from a median annual reduction of 37 minutes in patients at initial
      Hoehn and Yahr stage 1 to 6.5 minutes in stage 3 patients (p < 0.001). Patients
      without tremor at onset, otherwise comparable to patients with tremor for
      baseline values of levodopa t1/2eq, disease severity, duration, and daily dose of
      levodopa, tended to show a higher rate of reduction in levodopa t1/2eq than
      patients with tremor. Overall, patients' annual reduction in levodopa t1/2eq over
      baseline values averaged 17+/-9%. CONCLUSIONS: These results are in keeping with
      PET findings on the objective assessment of idiopathic parkinsonism evolution,
      and they support the suggestion that levodopa pharmacodynamic modeling may offer
      a practical clinical tool to assess indirectly the functional integrity of the
      nigrostriatal dopaminergic system over time in parkinsonian patients.

PMID- 9781533
TI  - Molecular and clinical studies in SCA-7 define a broad clinical spectrum and the
      infantile phenotype.
AB  - OBJECTIVE: To screen for the SCA-7 mutation in autosomal dominant cerebellar
      ataxia (ADCA) families and study genotype/phenotype correlations. BACKGROUND: The
      association of cerebellar ataxia and progressive pigmentary macular dystrophy
      clinically defines a distinct form of ADCA classified as SCA-7. SCA-7 is caused
      by expansion of a highly unstable CAG repeat that lies in the coding region of a
      novel gene on chromosome 3p12-13. METHODS: We screened 51 ADCA kindreds, in which
      SCA-1, SCA-2, SCA-3, and SCA6 mutations had been excluded, for the SCA-7 mutation
      using primers that specifically amplify the SCA-7 CAG repeat. RESULTS: The SCA-7
      mutation was identified in 10 independent families. Normal alleles ranged from 7
      to 16 repeats; expanded alleles ranged from 41 to 306 repeats. One allele with 36
      repeats was found in an asymptomatic individual carrying an at-risk haplotype.
      SCA-7 presents a wide spectrum of clinical features including visual loss,
      dementia, hypoacusia, severe hypotonia, and auditory hallucinations. Juvenile SCA
      7 occurs on maternal and paternal transmission of the mutation, whereas the
      infantile form occurs only on paternal transmission. An infant of African
      American descent carried the largest SCA-7 expansion (306 CAG repeats) and had
      severe hypotonia, congestive heart failure, patent ductus arteriosus, cerebral
      and cerebellar atrophy, and visual loss. CONCLUSION: These data show a wide
      spectrum of phenotypic abnormalities in SCA-7 and define an infantile phenotype
      caused by the largest CAG repeat expansion described to date.

PMID- 9781534
TI  - Partial depletion and multiple deletions of muscle mtDNA in familial MNGIE
      syndrome.
AB  - OBJECTIVE: To describe the unique combination of partial depletion and multiple
      deletions of mitochondrial DNA (mtDNA) on muscle DNA analysis of three siblings
      with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). BACKGROUND:
      MNGIE is a relatively homogeneous autosomal recessive disorder characterized by
      gastrointestinal dysmobility, ophthalmoparesis, peripheral neuropathy,
      mitochondrial myopathy, and altered white matter signal at brain imaging. Muscle
      multiple mtDNA deletions have been found in about half of the described cases.
      METHODS: We studied three affected siblings (two were monozygotic twins) born to
      nonconsanguineous parents. Muscle mtDNA was investigated by quantitative Southern
      and Slot blot techniques and by PCR analysis. Morphologic confirmation in the
      muscle tissue was achieved by using in situ hybridization with a mtDNA probe
      complementary to an undeleted region and by DNA immunohistochemistry. RESULTS:
      All three patients showed ragged red (RRF) and cytochrome c oxidase-negative
      fibers, as well as partial deficiency of complexes I and IV. Southern and Slot
      blot analyses showed mtDNA depletion in all patients. Multiple mtDNA deletions
      were also detected by PCR analysis. In situ hybridization demonstrated an overall
      signal weaker than controls, with a relatively higher signal in RRF. Antibodies
      against DNA showed a decreased cytoplasmic network. CONCLUSIONS: The muscle
      histopathology and respiratory chain enzyme defects may be accounted for by the
      decreased mtDNA amount and by the presence of mtDNA deleted molecules; however,
      relative levels of mtDNA seem to correlate with life span in these patients. The
      combination of partial depletion and multiple deletions of mtDNA might indicate
      the derangement of a common genetic mechanism controlling mtDNA copy number and
      integrity.

PMID- 9781535
TI  - Clinical evidence of extraocular muscle fiber-type specificity of botulinum
      toxin.
AB  - OBJECTIVE: To compare the effects of botulinum toxin on static and dynamic
      aspects of eye movements, and thereby elucidate the mechanisms of its action on
      eye muscles. BACKGROUND: Laboratory evidence indicates that static alignment and
      saccades are subserved by different extraocular muscle fiber types, and botulinum
      toxin may cause specific dysfunction of the fibers controlling static alignment.
      Diplopia is a well-known side effect of periorbital botulinum toxin injections in
      humans, and may be a clinical correlate of the laboratory findings. METHODS:
      Search coil recording of eye movements was performed in one patient with systemic
      botulism, and in three patients with diplopia following periorbital injection of
      botulinum toxin A. RESULTS: In the patient with acute botulism, eye movement
      alignment, range, and saccadic velocity profiles were abnormal. In three patients
      with iatrogenic diplopia, static alignment was abnormal but movement range and
      saccadic velocities were within normal limits. Edrophonium improved the range of
      movements and saccadic velocities in the patient with systemic botulism but was
      ineffective in reversing ocular misalignment in the one iatrogenic patient to
      whom it was administered. CONCLUSIONS: Precise alignment is subserved by orbital
      singly innervated muscle fibers, and the effects of botulinum toxin are greatest
      on these fibers. This predilection is apparent when the toxin dose is very small,
      as must have been the case in our patients with iatrogenic diplopia. The lack of
      a response to edrophonium probably reflects structural damage to muscle fibers.
      In contrast, larger doses of toxin produce an acute dysfunction of all
      extraocular muscle fiber types, which is responsive to edrophonium and
      consequently reflects partial blockade at the neuromuscular junction.

PMID- 9781536
TI  - Antibodies from ALS patients inhibit dopamine release mediated by L-type calcium
      channels.
AB  - OBJECTIVE: To examine the presence of anti-L-type calcium channel antibodies in
      the serum of ALS patients. BACKGROUND: Autoimmunity has been hypothesized as one
      of the mechanisms underlying the pathogenesis of sporadic ALS. Previous studies
      reported that sera from patients with sporadic ALS contain antibodies against
      voltage-gated calcium channels (L-type and P-type), but others do not support
      these findings. METHODS: Regulated secretion of tritiated dopamine ([3H]DA) in
      PC12 cells is mediated exclusively by calcium entry through L-type calcium
      channels. To examine whether purified ALS immunoglobulin G (IgG) inhibits [3H]DA
      release by interfering with calcium entry through L-type calcium channels, evoked
      release in PC12 cells was determined in the presence of ALS IgG. This functional
      assay provides a sensitive way to examine L-type calcium channel interaction with
      IgG from ALS patients. RESULTS: A significant inhibition of depolarization-evoked
      [3H]DA release (32+/-4%) was observed by purified IgG from ALS patients compared
      with control subjects (11+/-2%; p < 0.01). Significant inhibition by IgG occurred
      in 79% (15/19) of the ALS patients compared with only 29% (5/17) in the control
      group (p < 0.01). The level of calcium channel inhibition by ALS IgG correlated
      positively with disease duration (r = 0.68; p < 0.01) and correlated negatively
      with age (r = -0.48; p < 0.05). CONCLUSIONS: These results confirm the presence
      of antibodies against the L-type calcium channel in the majority of sera from ALS
      patients, supporting their role in the pathogenesis of ALS.

PMID- 9781537
TI  - A proton magnetic resonance spectroscopic study in ALS: correlation with clinical
      findings.
AB  - OBJECTIVE: To evaluate neuronal dysfunction in the motor region subcortical white
      matter in ALS using volumetric localized proton magnetic resonance spectroscopy
      (1H-MRS). METHODS: Sixteen patients with E1 Escorial definite, probable, or
      possible ALS and eight healthy age-matched control subjects were studied. The ALS
      patients were divided into those with limb onset (n = 8) and those with bulbar
      onset (n = 8). Measurements of the metabolic ratios N-acetylaspartate
      (NAA)/creatine and phosphocreatine (Cr+PCr), NAA/choline (Cho), and Cho/(Cr+PCr)
      were correlated with clinical assessments. RESULTS: We found no differences in
      the metabolic peak area ratios in the motor region when comparing the total ALS
      group and the control subjects. However, correlations were found between the
      NAA/(Cr+PCr) ratio and the E1 Escorial category (p = 0.03), the ALS severity
      scale (p = 0.01), and the Medical Research Council score (p = 0.06). No
      correlations were found between the NAA/(Cr+PCr) ratio and the Ashworth
      Spasticity Scale, reflex score, or disease duration (p > 0.16). Bulbar-onset
      patients had a lower NAA/(Cr+PCr) ratio in the motor region compared with limb
      onset patients (p = 0.03). CONCLUSION: In vivo 1H-MRS of the subcortical white
      matter in the motor region is unlikely to be sensitive enough to detect early
      disease changes in ALS because there is considerable overlap between the
      metabolic peak area ratios from patients with ALS and normal control subjects.
      However, changes in the NAA/(Cr+PCr) metabolic peak area ratios correlate with
      clinical measures of disease severity, and this measure may be useful in
      monitoring disease progression.

PMID- 9781538
TI  - The spectrum of antecedent infections in Guillain-Barre syndrome: a case-control
      study.
AB  - OBJECTIVE: To determine which antecedent infections are specifically associated
      with the Guillain-Barre syndrome (GBS). BACKGROUND: Infections with many agents
      have been reported preceding GBS. Some infections are related to specific
      clinical and immunologic subgroups in GBS. Most agents were reported in case
      reports and uncontrolled small series of GBS patients only, and their relation to
      GBS and its subgroups remains unclear. METHOD: A serologic study for 16
      infectious agents in 154 GBS patients and 154 sex- and age-matched controls with
      other neurologic diseases. Acute phase, pretreatment samples were used from
      clinically well-defined GBS patients. The seasonal distribution of serum sampling
      in the GBS and control group was the same. RESULTS: Multivariate analysis showed
      that in GBS patients, infections with Campylobacter jejuni (32%), cytomegalovirus
      (13%), and Epstein-Barr virus (10%) were significantly more frequent than in
      controls. Mycoplasma pneumoniae infections occurred more often in GBS patients
      (5%) than in controls in univariate analysis. Infections with Haemophilus
      influenzae (1%), parainfluenza 1 virus (1%), influenza A virus (1%), influenza B
      virus (1%), adenovirus (1%), herpes simplex virus (1%), and varicella zoster
      virus (1%) were also demonstrated in GBS patients, but not more frequently than
      in controls. C. jejuni infections were associated with antibodies to the
      gangliosides GM1 and GD1b and with a severe pure motor form of GBS.
      Cytomegalovirus infections were associated with antibodies to the ganglioside GM2
      and with severe motor sensory deficits. Other infections were not related to
      specific antiganglioside antibodies and neurologic patterns. CONCLUSIONS: Recent
      infections with C. jejuni, cytomegalovirus, Epstein-Barr virus, and M. pneumoniae
      are specifically related to GBS. The variety of infections may contribute to the
      clinical and immunologic heterogeneity of GBS.

PMID- 9781539
TI  - Early onset, autosomal recessive muscular dystrophy with Emery-Dreifuss phenotype
      and normal emerin expression.
AB  - OBJECTIVE: To describe the clinical and histopathologic picture of a childhood
      onset, severe variant of scapuloperoneal MD with rigidity of the spine.
      BACKGROUND: Rigidity of the spine is a feature of numerous syndromes, including X
      linked Emery-Dreifuss MD, Bethlem myopathy, and the rigid spine syndrome. These
      are, however, relatively static or very slowly progressive neuromuscular
      disorders, usually associated with preserved ambulation into adult life. PATIENTS
      AND METHODS: Five unrelated children (three boys and two girls) presented in the
      first 2 years of life with poor neck control, waddling gait, and frequent falls.
      Early wasting of the distal leg muscles, biceps, triceps, and neck muscles was
      noted in all patients, and all had contractures and severe rigidity of the spine.
      The condition progressed rapidly, and all patients lost ambulation before the age
      of 8 years. Cardiac function was normal in all. RESULTS: Creatine kinase was
      moderately elevated in all, and muscle biopsy specimens showed nonspecific
      dystrophic changes with normal expression of dystrophin, the sarcoglycans, and
      laminin alpha2, alpha5, beta1, and gamma1 chains. Emerin expression was normal in
      two of the boys whose tissue was available for study. CONCLUSIONS: The
      distribution of weakness, wasting, and contractures of the patients described
      resembled Emery-Dreifuss MD, but the rapid progression of weakness and
      contractures and the involvement of both sexes together with normal emerin
      expression suggest that this form is not X-linked Emery-Dreifuss MD. We suggest
      that these patients represent a severe MD characterized by early onset distal
      wasting and severe rigidity of the spine, with probable autosomal recessive
      inheritance.

PMID- 9781541
TI  - Initial and follow-up screening for aneurysms in families with familial
      subarachnoid hemorrhage.
AB  - BACKGROUND AND OBJECTIVE: In families with two or more relatives with
      subarachnoid hemorrhage (SAH), other first-degree relatives have an increased
      risk of SAH. We studied the presence of unruptured intracranial aneurysms in 125
      members of 23 families with familial SAH, defined as two or more affected first
      degree relatives, in a cross-sectional design. METHODS: MR angiography was
      performed in 116 relatives; CT angiography was performed in the remaining 9
      relatives because they had been treated for intracranial aneurysms in the past.
      RESULTS: Overall, we found 16 aneurysms in 10 of 125 relatives (8%; 95% CI, 4 to
      14%). Of the nine patients with previous surgery for ruptured or unruptured
      intracranial aneurysms, three had new aneurysms. Two factors were associated with
      a significantly higher risk of intracranial aneurysms: 1) a history of treatment
      for ruptured or unruptured intracranial aneurysms (relative risk 5.5; 95% CI, 1.7
      to 17.8) and 2) having three or more affected relatives (relative risk 3.3; 95%
      CI, 1.0 to 10.6). Siblings tended to have a higher risk of intracranial aneurysms
      than did children of SAH patients, although the difference was not significant.
      CONCLUSIONS: Because the yield is high, screening is recommended in first-degree
      members of families with familial SAH. Repeated screening should be considered in
      relatives who have been treated for familial intracranial aneurysms.

PMID- 9781540
TI  - Loss of catecholaminergic neurons in the medullary reticular formation in
      myotonic dystrophy.
AB  - OBJECTIVE: To clarify the possible relation between the extent of involvement of
      catecholaminergic neurons and the presence of alveolar hypoventilation in
      patients with myotonic dystrophy (MyD). BACKGROUND: Respiratory insufficiency has
      been reported frequently in MyD patients. Recent data support the hypothesis that
      this respiratory failure results from a primary dysfunction of the CNS. METHODS:
      The authors performed a quantitative immunoreactive study of tyrosine hydroxylase
      immunoreactive (TH+) neurons linked to hypoventilation in the dorsal central
      medullary nucleus (DCMN), the ventral central medullary nucleus (VCMN), and the
      subtrigeminal medullary nucleus (SMN)--where the autonomic respiratory center is
      thought to be located--in eight MyD patients and in 10 age-matched control
      subjects. Alveolar hypoventilation of the central type was present in three of
      the MyD patients but not in the remaining MyD patients or the control subjects.
      RESULTS: The densities of TH+ neurons of the DCMN, the VCMN, and the SMN in MyD
      patients with hypoventilation were significantly lower than in those without
      hypoventilation (p < 0.02, p < 0.01, and p < 0.01, respectively) and control
      subjects (p < 0.01, p < 0.01, and p < 0.01, respectively). CONCLUSIONS: These
      data suggest that the loss of TH+ neurons of the DCMN, the VCMN, and the SMN is
      associated with the presence of hypoventilation in MyD and may be an important
      feature of MyD.

PMID- 9781542
TI  - MR appearance of an intracranial dural arteriovenous fistula leading to cervical
      myelopathy.
AB  - OBJECTIVE: To report the MRI, myelographic, and angiographic findings as well as
      the clinical and radiologic time course of an intracranial dural arteriovenous
      fistula (DAVF) leading to cervical myelopathy; and to review the pertinent
      literature. BACKGROUND: Cervical myelopathy from an intracranial DAVF draining
      into spinal medullary veins is extremely uncommon. However, knowledge about the
      MR features of these lesions is important because an improper diagnosis might
      result in delayed or incorrect treatment. METHODS: In a patient with progressive
      cervical myelopathy, T2- and proton density (PD)-weighted MRI, contrast-enhanced
      T1-weighted images, and a contrast-enhanced MR angiogram of the cervical spinal
      cord were acquired. Additionally, intraarterial digital subtraction angiography
      (DSA) of the right and left common carotid arteries was performed. RESULTS: MRI
      findings included swelling of the cervical spinal cord, hyperintensity of the
      cervical cord on T2- and PD-weighted MRI, and an enlarged vessel at the ventral
      surface of the cord on MR angiography. No parenchymal contrast enhancement of the
      spinal cord was noted on T1-weighted MRI. DSA revealed an intracranial DAVF fed
      by four branches of the left external carotid artery and draining into spinal
      medullary veins. The fistula was treated with endovascular embolization, leading
      to considerable clinical improvement of the patient. CONCLUSIONS: To avoid an
      improper diagnosis or a delayed or incorrect treatment of myelopathy resulting
      from an intracranial DAVF, cerebral intraarterial angiography may be indicated in
      cases of otherwise unexplainable cervical myelopathy.

PMID- 9781543
TI  - Adult brainstem gliomas.
AB  - OBJECTIVE: To evaluate prognostic factors and survival of adult patients with
      brainstem gliomas. BACKGROUND: Brainstem glioma is a disease found primarily in
      children, with a median survival of only 9 to 12 months. However, the prognosis
      and survival of adults with this disease has not been determined with precision.
      METHODS: We conducted a retrospective analysis of patients older than 16 years at
      Memorial Sloan-Kettering Cancer Center with histologically proved or presumed
      brainstem glioma diagnosed between 1989 and 1997. We assessed the effect of
      gender, age at diagnosis, cranial nerve involvement, duration of symptoms,
      exophytic component, MRI enhancement, site of disease, treatment, and Karnofsky
      performance status on survival. RESULTS: Twenty-three patients were identified,
      but complete information was available in only 19 (12 males and 7 females).
      Patients ranged in age from 17 to 70 years (median, 40 years). Twelve patients
      were treated with radiotherapy at diagnosis and seven were observed, three of
      whom received subsequent radiotherapy. Median survival is 54 months (range, 3 to
      98 months) and the 5-year survival is 45%. There was a trend for patients with a
      higher performance status at diagnosis to have longer survival, but this did not
      reach statistical significance. Other factors did not affect survival.
      CONCLUSION: Adults with brainstem gliomas may survive significantly longer than
      children, suggesting the disease may be less aggressive in adults. Furthermore,
      some patients with a long duration of symptoms or tectal or cervicomedullary
      tumors may be managed initially with observation alone.

PMID- 9781545
TI  - T-cell receptor analysis in anti-Hu associated paraneoplastic encephalomyelitis.
AB  - OBJECTIVE: To analyze the T-cell receptor (TCR) repertoire in the inflammatory
      infiltrates of the nervous system and tumor of patients with anti-Hu associated
      paraneoplastic encephalomyelitis and sensory neuronopathy (PEM/SN). BACKGROUND:
      In PEM/SN, the pathogenic role of the infiltrating T cells is speculative. TCR
      analysis may establish whether these lymphocytes are attracted nonspecifically by
      a proinflammatory environment or are driven by a specific antigen or
      superantigen. METHODS: We examined frozen tissues of seven patients with PEM/SN
      using immunohistochemical and PCR analysis. Of 62 tissue blocks from seven
      patients, 19 blocks from five patients had >100 CD3+ cells per section
      infiltrating the nervous system or tumor. These infiltrates allowed screening of
      the TCR Vbeta family repertoire using a panel of 18 antibodies that recognize
      family-specific regions of most TCR Vbeta families against which antibodies have
      been generated. To distinguish between antigen-driven clonal and superantigen
      driven family expansion, we extracted RNA from frozen tissue and performed
      reverse transcriptase (RT)-PCR analysis followed by subcloning and sequencing of
      the antigen-specific CDR3 region of the TCR Vbeta chain. RESULTS: All five
      patients showed a limited Vbeta repertoire. An overrepresentation (>10% of total
      CD3+) of certain Vbeta families was identified in three patients (as high as 45%
      of total CD3+), which consisted mainly of CD8 + cells. CDR3 sequences obtained
      from one patient revealed an in situ expansion of two clones in the amygdala (one
      at a frequency of 57%) and four clones in the tumor. CONCLUSION: These findings
      suggest that an antigen-driven oligoclonal cytotoxic T-cell response plays a role
      in the pathogenesis of anti-Hu associated PEM/SN.

PMID- 9781546
TI  - Early structural changes in acute MS lesions assessed by serial magnetization
      transfer studies.
AB  - BACKGROUND: Whether acute MS lesions are primarily inflammatory or demyelinative
      is unresolved. Our study examined acute MS lesions longitudinally by quantitative
      magnetization transfer (MT), an MRI technique that identifies tissue integrity
      and destruction. METHODS: Four MS patients were studied by serial MRI including
      MT, conventional T2-weighted images, and postgadolinium T1-weighted images for 9
      to 12 months. In 15 new lesions, the MT ratio (MTR) was calculated
      retrospectively. RESULTS: In 13 lesions, a marked decrease in the MTR was present
      early during the first 2 months after the onset of the lesion and was followed by
      a variable increase. In two other lesions, the MTR progressively declined.
      CONCLUSIONS: These results suggest that major early structural changes compatible
      with demyelination and followed by remyelination and gliosis, or by continuous
      demyelination, occur in new MS lesions. The various MTR profiles provide in vivo
      confirmation of the current knowledge of the progression in MS lesions.
      Furthermore, MTR may be used to monitor in vivo drug efficacy in new MS lesions.

PMID- 9781544
TI  - Response rate and prognostic factors of recurrent oligodendroglioma treated with
      procarbazine, CCNU, and vincristine chemotherapy. Dutch Neuro-oncology Group.
AB  - OBJECTIVES: To determine the response rate and factors correlated with response
      of oligodendroglial tumors to procarbazine, lomustine (CCNU), and vincristine
      (PCV) chemotherapy. DESIGN: Retrospective, observational multicenter study.
      METHODS: Patients treated with PCV or intensified PCV chemotherapy for a
      recurrent oligodendroglial tumor after surgery and radiation therapy with
      measurable disease were retrospectively evaluated for response. A 50% reduction
      in cross-sectional enhancing tumor area was considered a partial response.
      Stabilized or responding patients received six cycles of PCV unless unacceptable
      toxicity occurred. RESULTS: Fifty-two patients were included; median time to
      progression (MTP) for the entire group was 10 months. In 17% of patients a
      complete response (MTP, 25 months) was obtained, and in 46% a partial response
      (MTP, 12 months) was obtained. Median overall survival was 20 months. Although
      treatment was discontinued for toxicity in seven patients, it was generally well
      tolerated. The intensified PCV regimen was more toxic. Patients initially
      presenting with seizures and patients with tumor necrosis in histologic specimens
      had a better response rate in contrast to patients who had their first relapse
      within 1 year of first treatment (surgery and radiation therapy). CONCLUSIONS:
      Oligodendroglial tumors are chemosensitive, but most patients will have relapsed
      after 12 to 16 months. New studies must aim at improving initial treatment and
      second-line chemotherapy.

PMID- 9781547
TI  - Elevated serum and CSF levels of soluble CD30 during clinical remission in
      multiple sclerosis.
AB  - OBJECTIVE: To ascertain the presence of the Th2 response in MS patients by
      evaluating the level of soluble (s) CD30 across the clinical spectrum of MS and
      during relapse and remission. BACKGROUND: MS is considered a T-cell-mediated
      disorder with the immune attack dominated by a Thl cytokine response. Elevated
      levels of sCD30 have been associated with CD4+ cells that secrete Th2-type
      cytokines. METHODS: Levels of sCD30 were determined in the serum and CSF of
      patients with primary progressive MS, secondary progressive MS, relapsing
      remitting MS (RRMS), both in relapse and remission, and in patients with other
      inflammatory neurologic disease (IND) and noninflammatory neurologic disease
      (NIND). None of the patients were on immunomodulatory treatment. RESULTS: Higher
      serum levels of sCD30 were detected in all MS subgroups and IND patients compared
      with NIND patients. RRMS patients in remission had significantly higher levels
      than those in relapse (median, 45.7 U/mL versus 18.3 U/mL; p = 0.04).
      Significantly higher CSF levels were also found in all groups, except those with
      RRMS in relapse compared with NIND patients. Again, RRMS patients in remission
      had higher CSF sCD30 levels compared with those in relapse (median, 4.0 U/mL
      versus 3.0 U/mL; p = 0.08). CONCLUSIONS: Serum and CSF levels of sCD30 are
      increased in MS, particularly during remission. The results provide additional
      evidence for the presence of a Th2 response and indicate that sCD30 may be of
      value as a marker of lesion resolution.

PMID- 9781548
TI  - Fracture history and bone loss in patients with MS.
AB  - OBJECTIVES: We have previously shown that MS patients have significantly reduced
      bone mass and a high prevalence of abnormal vitamin D status. The object of this
      study was to characterize the frequency of adulthood fractures in MS patients,
      prospectively determine rates of bone loss in MS, and determine whether vitamin D
      status is a predictor of bone loss. METHODS: MS patients (36 women, 18 men) were
      compared with age- and gender-matched healthy controls (35 women, 14 men). Bone
      mass was performed by dual x-ray absorptiometry at baseline and at 12-month
      intervals over 2 years. RESULTS: Fractures in the absence of major trauma had
      occurred in 2% of controls and 22% of MS patients (p < 0.002). Over the 2 years
      of prospective follow-up, both women and men with MS lost substantially more bone
      in the femoral neck than did controls (3% and 6% per year in pre- and
      postmenopausal women with MS versus 0.5% and 0.8% per year in controls; 7.3% per
      year in men with MS versus 1.6% per year in controls). Bone loss in the spine was
      also greater in women with MS than in controls (1.6 to 3.5% per year loss in MS
      patients versus no change in controls). Duration of steroid treatment beyond 5
      months and ambulatory status were both predictors of bone loss. Bone loss in the
      spine occurred faster in MS patients with low (<20 ng/mL) 25-hydroxyvitamin D
      levels (1.9% per year, p < 0.04), whereas in those with normal 25-hydroxyvitamin
      D levels, bone loss was insignificant. At the femoral neck, bone loss was
      substantial in all patients, but was somewhat faster in the group with low levels
      of 25-hydroxyvitamin D (5.6% per year, p < 0.0001) compared with the group with
      high levels of 25-hydroxyvitamin D (4.3% per year, p = 0.03). CONCLUSIONS: MS
      patients have more frequent fractures and lose bone mass more rapidly than do
      their healthy age- and gender-matched peers, in part related to insufficient
      vitamin D. Vitamin D repletion in MS patients who are deficient might reduce, to
      some extent, the rate of bone loss and decrease osteoporosis-related fractures.

PMID- 9781549
TI  - Nortriptyline versus amitriptyline in postherpetic neuralgia: a randomized trial.
AB  - OBJECTIVE (BACKGROUND): Amitriptyline (AT) is a standard therapy for postherpetic
      neuralgia (PHN). Our hypothesis was that nortriptyline (NT), a noradrenergic
      metabolite of AT, may be more effective. METHODS: A randomized, double-blind,
      crossover trial of AT versus NT was conducted in 33 patients. RESULTS: Thirty-one
      patients completed the trial. Twenty-one of 31 (67.7%) had at least a good
      response to AT or NT, or both. We found no difference with regard to relief of
      steady, brief, or skin pain by visual analog scales for pain and pain relief;
      mood; disability; satisfaction; or preference between the two drugs. Intolerable
      side effects were more common with AT. Most patients (26/33) were not depressed,
      and most responding showed no change in rating scales for depression despite the
      occurrence of pain relief. CONCLUSIONS: We concluded that this study provides a
      scientific basis for an analgesic action of NT in PHN because pain relief
      occurred without an antidepressant effect, and that although there were fewer
      side effects with NT, AT and NT appear to have a similar analgesic action for
      most individuals.

PMID- 9781550
TI  - Lamotrigine-associated anticonvulsant hypersensitivity syndrome.
AB  - We systematically reviewed and analyzed published and unpublished cases of
      lamotrigine-associated adverse drug reactions consistent with the features of the
      anticonvulsant hypersensitivity syndrome (AHS) to identify characteristics of the
      syndrome. We identified 26 cases (mean age, 28+/-18 years; range, 3.5 to 74
      years; 54% female), of which nine were published. The characteristics of the
      syndrome associated with lamotrigine are comparable to AHS induced by older
      aromatic anticonvulsants.

PMID- 9781551
TI  - Postictal nose wiping: a lateralizing sign in temporal lobe complex partial
      seizures.
AB  - We report postictal nose wiping as a postictal symptom of localizing and
      lateralizing significance in focal epilepsy. We reviewed videotapes of 444 focal
      seizures in 101 patients who underwent prolonged video and EEG monitoring during
      presurgical epilepsy evaluation, and observed postictal nose wiping in 51.3% of
      76 patients with temporal lobe epilepsy. The hand used to perform postictal nose
      wiping was ipsilateral to the side of seizure origin in 86.5% of all seizures and
      in 97.3% of all patients. We conclude that postictal nose wiping is a common,
      easily assessed symptom after focal seizures of temporal lobe origin that
      provides reliable lateralizing information on the side of seizure onset.

PMID- 9781552
TI  - Worsening seizures after surgery for focal epilepsy due to emergence of primary
      generalized epilepsy.
AB  - Our patient underwent right anteromesial temporal resection at 17 years of age
      for intractable complex partial seizures due to hippocampal sclerosis, and then
      developed juvenile myoclonic epilepsy after a change in medication. Postoperative
      seizures ceased after a change to valproate monotherapy. Our patient reminds us
      to remain aware that generalized and focal epilepsy may coexist as an unusual
      cause for surgical failure. We feel that these patients may still be favorable
      candidates for epileptic surgery, as long as the focal epileptogenic zone is
      amenable to resection and the generalized epilepsy appears to be readily
      controllable.

PMID- 9781553
TI  - Kufs' disease presenting as late-onset epilepsia partialis continua.
AB  - A 64-year-old woman, who had no personal or family history of neurologic
      diseases, had an 18-month history of epilepsia partialis continua (EPC)
      associated with a moderate intellectual deterioration and subtle extrapyramidal
      rigidity. There was no photosensitive response. A thorough laboratory
      investigation was unremarkable. A biopsy of the rectal mucosa revealed abundant
      fingerprint profiles diagnostic of Kufs' disease (KD). Our case expands the
      clinical picture of KD and suggests that such a diagnosis should be considered in
      adult-onset EPC.

PMID- 9781554
TI  - Bilateral temporal lobe necrosis after radiotherapy: confounding SPECT results.
AB  - A patient with seizures and a contrast-enhancing temporal lesion after radiation
      therapy for a chondrosarcoma of the nasal septum is described. To differentiate
      between radiation necrosis and recurrent tumor, thallium-201 (201Tl) SPECT was
      used. 201Tl SPECT revealed high local accumulation suggesting tumor growth;
      however, pathologic examination demonstrated focal necrosis with reactive changes
      but without tumor. The 201Tl SPECT findings in this patient demonstrate a
      possible diagnostic pitfall in differentiating recurrent tumor from radiation
      necrosis.

PMID- 9781555
TI  - Sneddon's syndrome: neuro-ophthalmologic manifestations in a possible autosomal
      recessive pattern.
AB  - Sneddon's syndrome is a rare neurodermatologic disorder that is manifested by
      multiple cerebrovascular accidents and livedo reticularis. The authors describe
      two siblings from one family with Sneddon's syndrome, suggesting autosomal
      recessive inheritance. The propositus presented with internuclear ophthalmoplegia
      and ophthalmic artery occlusion. These manifestations as well as the autosomal
      recessive inheritance have not yet been reported in Sneddon's syndrome.

PMID- 9781556
TI  - CSF abnormalities in patients with aceruloplasminemia.
AB  - Aceruloplasminemia is a disorder of iron metabolism characterized by degeneration
      of the retina and basal ganglia. CSF from affected patients showed a threefold
      increased iron concentration that was associated with increased superoxide
      dismutase activity and lipid peroxidation products. These findings support the
      hypothesis that iron-mediated lipid peroxidation contributes to neurodegeneration
      in patients with aceruloplasminemia. Such measurements may have value in
      assessing disease progression as well as the results of iron chelation and other
      therapeutic interventions.

PMID- 9781557
TI  - Mitochondrial DNA depletion in a patient with long survival.
AB  - We studied a 29-year-old woman with myopathy since childhood with evidence of
      mitochondrial DNA (mtDNA) depletion. Muscle biopsy sample showed cytochrome c
      oxidase (COX)-negative fibers. Biochemistry showed COX deficiency. Southern blot
      analysis showed 76% depletion of mtDNA as compared with controls. This patient's
      clinical course suggests that long survival is possible in some patients with
      mtDNA depletion.

PMID- 9781558
TI  - Antineurofilament antibodies in postpolio syndrome.
AB  - We determined the levels of antineurofilament antibodies in 29 patients with
      postpolio syndrome (PPS), 26 stable postpolio (PP) patients, 22 patients with
      ALS, and 20 normal controls (NCs). Patients with PPS had higher antibody levels
      to cholinergic neurofilaments than did all other groups. PP patients and those
      with ALS had antibody levels similar to those of NCs. The antibody binding level
      showed no relation to the age of the patients, duration of disease, or motor
      score.

PMID- 9781559
TI  - Distal sensory axonopathy after sarin intoxication.
AB  - A 51-year-old man inhaled sarin during a terrorist attack on the Tokyo subway
      system and died 15 months later. Neuropathologic examination revealed marked
      nerve fiber decrease in the sural nerve, moderate nerve fiber loss in the sciatic
      nerve, and unremarkable dorsal root ganglia, dorsal roots, and posterior column
      of the spinal cord. This pathology is consistent with dying-back degeneration of
      the peripheral nervous system and could represent a late sequela of sarin
      intoxication.

PMID- 9781560
TI  - The long-term clinical outcome of myasthenia gravis in patients with thymoma.
AB  - We compared 42 myasthenia gravis (MG) patients with thymoma with 42 generalized
      MG patients without thymoma using a modified Osserman classification. The mean
      Osserman grades at diagnosis, 6 months, and 5 and 10 years post-thymectomy did
      not differ between groups. Our results indicate that thymoma is not a negative
      determinant for the long-term clinical outcome of MG.

PMID- 9781561
TI  - Coma in fulminant pneumococcal meningitis: new MRI observations.
AB  - We report a 45-year-old man with fulminant pneumococcal meningitis. Fluid
      attenuated inverse ratio MR images showed the ravaging consequences of occlusive
      vasculopathy and a transient purulent basal exudate. Bilateral thalamic lesions
      may have explained the failure to awaken despite appropriate antibiotic therapy.

PMID- 9781563
TI  - Post-traumatic shoulder 'dystonia': persistent abnormal postures of the shoulder
      after minor trauma.
AB  - The authors describe two patients with fixed shoulder elevation and prominent
      regional muscle hypertrophy that developed within days after local minor injury.
      The condition lacked several typical features of dystonia, such as the presence
      of torsional movements, task specificity, or relief by antagonistic gestures.
      These patient reports add to the growing literature indicating that persistent
      post-traumatic abnormal postures and muscle hypertrophy in different body parts
      may be a distinct response of the nervous system to injury.

PMID- 9781562
TI  - Rapid diagnosis of varicella zoster virus infection in acute facial palsy.
AB  - Patients with zoster sine herpete and Ramsay Hunt syndrome without pathognomonic
      vesicles at the initial visit are often misdiagnosed with Bell's palsy and
      treated without antiviral agents. With PCR, we found that varicella zoster virus
      genomes were frequently detectable in auricular skin exudate from patients with
      zoster sine herpete or Ramsay Hunt syndrome before the appearance of vesicles.

PMID- 9781564
TI  - Right-side neglect in Alzheimer's disease.
AB  - Unilateral neglect--the inability to pay attention to events occurring on one
      side of space--usually occurs for left-side events after focal right-hemisphere
      damage. We report a 73-year-old woman with probable AD and no evidence of focal
      brain lesions who showed signs of right-side neglect and extinction. Neglect was
      more severe after 1 year. Neuroimaging techniques demonstrated an asymmetry of
      cortical involvement, with cortical atrophy and hypoperfusion predominant in the
      left posterior regions. Unilateral neglect should be assessed systematically in
      AD.

PMID- 9781565
TI  - Nervous system dysfunction in Waldenstrom's macroglobulinemia: response to
      treatment.
AB  - A patient presented with a peripheral neuropathy and was found to have
      Waldenstrom's macroglobulinemia with high serum titers of antibodies to myelin
      associated glycoprotein. He developed parkinsonism that was poorly responsive to
      levodopa. He failed conventional therapy and was treated with autologous bone
      marrow transplantation, which resulted in improvement of the neuropathy but not
      his parkinsonism. Critical cytoreduction in the B-cell clone may be necessary for
      improvement of the neuropathy of Waldenstrom's macroglobulinemia.

PMID- 9781566
TI  - Dual infective pathology in patients with cryptococcal meningitis.
AB  - Coinfection of the nervous system by two distinct nonviral organisms is uncommon
      and often undiagnosed. Medical teaching emphasizes that a single pathologic
      process should be sought; however, in the presence of severe immunocompromise
      this approach may not hold true. We describe seven HIV-1 seropositive patients
      with cryptococcal meningitis, three of whom had a proven nervous system infection
      with a second organism: concurrent tuberculous meningitis, a tuberculoma, and the
      first documented case of cryptococcal meningitis and neurosyphilis.

PMID- 9781567
TI  - Diagnostic role of Mantoux test site biopsy in neurosarcoidosis.
AB  - We discuss a patient with sarcoidosis presenting with cranial neuropathy and a
      cerebral mass lesion evident on imaging. Also, we review from the literature six
      patients with sarcoidosis presenting with cerebral mass lesion. We emphasize the
      diagnostic role of Mantoux test site biopsy in patients with dominant or isolated
      neurologic presentation because the involved sites are not easily accessible and
      Kveim's test antigen is not commercially available.

PMID- 9781568
TI  - Devic's neuromyelitis optica: a prospective study of seven patients treated with
      prednisone and azathioprine.
AB  - Seven newly diagnosed patients with Devic's neuromyelitis optica were treated
      with long-term prednisone and azathioprine, and were followed every 2 months for
      at least 18 months. Their Expanded Disability Status Scale score improved
      significantly (mean at baseline, 9; mean at 18 months, 3; p < 0.005), and no
      relapses occurred for more than 18 months. Multicenter controlled studies are
      needed to prove the efficacy of this therapeutic regimen.

PMID- 9781569
TI  - Encouraging initial response of restless legs syndrome to pramipexole.
AB  - Restless legs syndrome (RLS) is a common condition that results in uncomfortable
      sensations and an urge to move the limbs. Two centers tested a new dopamine
      agonist, pramipexole, in 23 patients with RLS in a time-limited, open-label,
      clinical trial. After 4 weeks or more, 19 patients reported significant
      improvement as assessed by the short International Restless Legs Syndrome Study
      Group questionnaire (p < 0.0001). These encouraging preliminary results justify
      larger, controlled trials for pramipexole in patients with RLS.

PMID- 9781570
TI  - Neuralgic amyotrophy associated with hypersensitivity to lamotrigine.

PMID- 9781571
TI  - Stimulation of the phrenic nerve as a complication of vagus nerve pacing in a
      patient with epilepsy.

PMID- 9781572
TI  - Lower limb tremor in Machado-Joseph disease.

PMID- 9781573
TI  - Chloroquine myopathy and neuropathy with elevated CSF protein.

PMID- 9781574
TI  - Asymptomatic McArdle's disease associated with hyper-creatine kinase-emia and
      absence of myophosphorylase.

PMID- 9781575
TI  - Guillain-Barre syndrome after thalamotomy for tremor in MS.

PMID- 9781576
TI  - Patterns of hysterical hemianopia.

PMID- 9781577
TI  - Conflicts of interest in neurology.

PMID- 9781578
TI  - Evaluation and management of intracranial mass lesions in AIDS: Report of the
      Quality Standards Subcommittee of the American Academy of Neurology.

PMID- 9781579
TI  - Evaluation and management of intracranial mass lesions in AIDS: Report of the
      Quality Standards Subcommittee of the American Academy of Neurology.

PMID- 9781580
TI  - Evaluation and management of intracranial mass lesions in AIDS: Report of the
      Quality Standards Subcommittee of the American Academy of Neurology.

PMID- 9781581
TI  - Evaluation and management of intracranial mass lesions in AIDS: Report of the
      Quality Standards Subcommittee of the American Academy of Neurology.

PMID- 9781582
TI  - Narrowing the evidence-practice gap: strengthening the link between research and
      clinical practice.

PMID- 9781583
TI  - Clinical trials, outcomes, and statistics: how better can be worse.

PMID- 9781584
TI  - Delayed postanoxic demyelination registry.

PMID- 9781585
TI  - Delayed postanoxic demyelination registry.

PMID- 9781586
TI  - The 5-year risk of MS after optic neuritis.

PMID- 9781587
TI  - The 5-year risk of MS after optic neuritis.

PMID- 9781588
TI  - The 5-year risk of MS after optic neuritis.

PMID- 9781589
TI  - The added value of MRI measures of atrophy in the diagnosis of AD.

PMID- 9781590
TI  - Increased risk of mortality in AD patients with higher education?

PMID- 9781591
TI  - Assessment of quadriceps oxygenation in patients with myopathies by near infrared
      spectroscopy.

PMID- 9781592
TI  - Cat-scratch encephalopathy.

PMID- 9781593
TI  - Stage I adenocarcinoma of the cervix: does lesion size affect treatment options
      and prognosis?
AB  - A retrospective analysis of 93 patients with International Federation of
      Gynecology and Obstetrics stage I adenocarcinoma of the cervix was performed to
      determine the significance of tumor size, patient age, tumor grade, lymph node
      status, and primary treatment modality as prognostic variables of 5-year survival
      and 5-year progression-free survival (PFS). Multivariate analysis demonstrated
      that patient age and tumor grade were significant variables prognostic of
      survival (p < 0.01 and p = 0.01, respectively). Tumor size was a significant (p <
      0.01) prognostic variable of PFS in a multivariate model that included tumor size
      and patient age. An important advantage in survival and PFS for patients with
      lesions smaller than 3 cm compared with those patients with lesions 3 cm or more
      was observed (92% vs. 76% and 89% vs. 67%, respectively). Among surgically
      treated patients, survival and PFS among patients with lesions smaller than 3 cm
      were significantly improved compared with patients with tumors 3 cm or more (97%
      vs. 77% [p = 0.03] and 90% vs. 69% [p = 0.03], respectively). Significant
      improvement in survival and PFS was observed among patients with lesions smaller
      than 3 cm who were treated with surgery compared with those who received
      radiation therapy (97% vs. 77% [p = 0.03] and 90% vs. 77% [p = 0.048],
      respectively).

PMID- 9781594
TI  - Arterial occlusions as a presenting feature of acute promyelocytic leukemia.
AB  - Arterial thrombosis as a presentation of acute promyelocytic leukemia is
      uncommon. The authors report a patient who presented with a clot in the left
      external iliac artery and pulmonary emboli. The literature is reviewed.

PMID- 9781596
TI  - Daily oral etoposide in patients with heavily pretreated metastatic breast
      cancer.
AB  - The objective of this phase II study was to evaluate the activity and toxicity of
      oral etoposide (50 mg/m2 daily for 21 days in 28-day cycles) in patients with
      heavily pretreated metastatic breast cancer. Thirty patients were entered into
      the study; all had clinical or radiologic evidence of disease progression, median
      age was 51 years, and the majority of patients (82%) had a Zubrod performance
      status equal to or lower than 1 and a median of 3 disease sites. All patients had
      received chemotherapy, and more than 80% had received 3 or more regimens. More
      than 70% of the patients had received taxanes as one of their previous therapies.
      Twenty-four and 28 patients were evaluable for tumor response and toxicity,
      respectively. One partial response was seen (<4%), and seven patients (25%)
      demonstrated stable disease with a median duration of four months. There was
      significant hematologic toxicity. In two patients therapy had to be stopped
      because of excessive toxicity, and five patients required hospitalization for
      neutropenic fever. Overall, 57% of patients experienced grade 2 or higher degree
      of neutropenia including two patients with grade 4 toxicity. Seventeen percent of
      patients developed grade 2 or greater thrombocytopenia, including one patient who
      experienced grade 4 toxicity, and 71% of the patients had grade 2 or more severe
      anemia including two patients with grade 4 toxicity. Oral etoposide has limited
      activity as third- or fourth-line agent and produces significant hematologic
      toxicity in patients with heavily pretreated metastatic breast cancer.

PMID- 9781595
TI  - Phase II trial of topotecan administered as a 21-day continuous infusion in
      previously untreated patients with stage IIIB and IV non-small-cell lung cancer.
AB  - Topotecan (9-dimethylaminoethyl-10-hydroxycamptothecin) is a topoisomerase I
      inhibitor. Twenty-six patients with stage IIIB or IV non-small-cell lung cancer
      (NSCLC) who had received no prior chemotherapy were treated in a multicenter
      study with topotecan 0.6 mg/m2/day for 21 days by continuous intravenous infusion
      every 28 days; this starting dose was decreased to 0.5 mg/m2/day in the last 23
      patients because of myelosuppression. There was one partial response, for a
      response rate of 4% (95% confidence interval, 0.1%-19.6%). Median survival was 9
      months. One-year survival was 39%. Of the 58 lung cancer symptoms at baseline,
      40% were resolved by the end of best response (all in the partial response
      patient, 62% in stable disease patients, 26% in progressive disease patients).
      Catheter-related infections complicated 19% of courses. Red-cell transfusions
      were given in 50% of courses. Toxicity included grade 4 neutropenia (4%), grade 3
      4 anemia (19%), grade 4 thrombocytopenia (8%), and catheter-related infections
      (19% courses). Although the major objective response rate was only 4%, patients
      treated with topotecan given as a 21-day continuous intravenous infusion
      experienced a decrease in cancer-related symptoms and a 1-year survival of 39%.

PMID- 9781597
TI  - Progesterone receptor status is a significant prognostic variable of progression
      free survival in advanced epithelial ovarian cancer.
AB  - The purpose of this study was to determine if tumor estrogen receptor (ER) or
      progesterone receptor (PR) status were significant prognostic variables of
      survival and progression-free survival among patients with International
      Federation of Gynecology and Obstetrics (FIGO) stage III and IV epithelial
      ovarian cancer. Tumor steroid receptor status was evaluated among 67 consecutive
      patients who underwent primary surgery from June 1983 through September 1990.
      Characteristics of receptor-negative and receptor-positive populations were
      compared by chi-square analysis. Univariate and multivariate analyses were used
      to identify variables prognostic of survival and progression-free survival. Fifty
      one of 67 patients (76.1%) had ER-positive tumors and 31 (46.3%) patients had PR
      positive tumors. Significant differences between receptor-positive and receptor
      negative populations were not observed. Neither univariate nor multivariate
      analysis identified ER or PR status as significant prognostic variables of
      survival (p = 0.93 and p = 0.06, respectively). Progesterone receptor-positive
      status was a significant prognostic variable of progression-free survival in both
      univariate (p = 0.03) and multivariate (p = 0.04) analyses even after adjustment
      for residual disease and patient age. Estrogen receptor status was not a
      significant prognostic indicator of progression-free survival in either
      univariate or multivariate analyses. Progesterone receptor-positive tumor status
      is shown to be an independent prognostic variable of improved progression-free
      survival among patients with advanced epithelial ovarian cancer.

PMID- 9781598
TI  - Biochemical modulation of 5-fluorouracil by methotrexate in patients with
      advanced gastric carcinoma.
AB  - A phase II trial was conducted to evaluate the efficacy and toxicity of a
      modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) (with leucovorin (LV)
      rescue) as first-line chemotherapy in patients with locally advanced (inoperable)
      or metastatic gastric carcinoma. From July 1993 through August 1996, 36 patients
      with advanced gastric carcinoma received a regimen that consisted of: MTX 200
      mg/m2 diluted in 250 ml normal saline by intravenous infusion over 20 minutes at
      hour 0; 5-FU 1,200 mg/m2 intravenous push injection at hour 20. Beginning 24
      hours after MTX administration all patients received LV 15 mg/m2 intramuscularly
      every 6 hours for six doses. Cycles were repeated every 15 days. One patient was
      not assessable for response. Objective regression was observed in 15 of 37
      patients (43%; 95% confidence interval, 26%-60%). One patient (3%) achieved
      complete response and 14 (40%) achieved partial response. No change was recorded
      in 14 patients (40%) and progressive disease was noted in six patients (17%). The
      median time to treatment failure was 7 months and the median survival was 12
      months. Toxicity was within acceptable limits but one therapy-related death
      resulting from severe leukopenia occurred. The dose-limiting toxicity was
      mucositis. Five episodes of grade 3 or 4 stomatitis were observed and caused
      dosage modifications of MTX and 5-FU. Biochemical modulation of 5-FU by MTX
      appears as an attractive modality in patients with advanced gastric cancer.
      Further investigation both in experimental and clinical fields is needed to
      clearly define its role and to design the best modulatory strategy.

PMID- 9781599
TI  - Gastric small-cell carcinoma in Japan: a case report and review of the
      literature.
AB  - The authors encountered a patient with primary gastric small-cell carcinoma
      (primary gastric SCC). Histologic examination revealed combined carcinoma
      containing non-small-cell elements such as adenocarcinoma and squamous cell
      differentiation. On preoperative biopsy, only well-differentiated adenocarcinoma
      was collected. Since gastric SCC was first reported in 1976, this type of
      carcinoma has been detected in 54 patients in Japan. Concerning these cases, the
      authors reviewed the light and/or electron microscopic findings of neuroendocrine
      granules, positive reaction for neuron-specific enolase staining, and the
      histologic type of resected specimens. There were only three patients positive
      for neuron-specific enolase in which light and electron microscopy demonstrated
      neuroendocrine granules. However, 50 patients (approximately 93%) overall
      satisfied at least one of these findings. Concerning the histologic
      characteristics of the resected specimens, multidirectional differentiation was
      more markedly observed compared with that in SCC of the lung. Adenocarcinomatous
      and/or squamous differentiation was observed in more than half the cases, and
      preoperative biopsy suggested carcinoma other than SCC or undifferentiated
      carcinoma in several cases.

PMID- 9781601
TI  - Improved survival in patients with advanced colorectal carcinoma failing 5
      fluorouracil who received irinotecan hydrochloride and have high intratumor C-fos
      expression.
AB  - This study determines the prognostic role of c-fos protein expression in patients
      with colon cancer who previously failed therapy with 5-fluorouracil (5-FU).
      Patients with advanced colorectal who were refractory to 5-FU therapy received
      irinotecan (CPT-11) by a 90-minute intravenous infusion at a dose of 125 mg/m2
      weekly for four weeks followed by a 2-week rest period were eligible for oncogene
      assessment. C-fos protein expression was evaluated using archival formalin-fixed,
      paraffin-embedded tumor tissue, and an automated immunoperoxidase histochemical
      technique. Thirty-five patients were found to have > 25% positive c-fos activity.
      Nine patients had no detectable c-fos expression. Characteristics of patient
      subgroups were not different, however, the median survival of patients with
      elevated c-fos expression from the time of treatment with CPT-11 was 436 days,
      whereas patients with no detectable c-fos expression had a median survival of 365
      days (p = 0.045). C-fos exhibits a casual role in the initiation of apoptosis and
      is implicated in differentiation and proliferation. It has been shown to
      correlate with poor survival in breast cancer, but improved survival in patients
      with astrocytic glioma. In this analysis, there is a suggestion that elevated c
      fos expression is a good prognostic marker for patients with refractory
      colorectal carcinoma.

PMID- 9781600
TI  - A randomized study of radiotherapy alone versus radiotherapy plus 5-fluorouracil
      and platinum in patients with inoperable, locally advanced squamous cancer of the
      esophagus.
AB  - Squamous cell cancer of the esophagus is the most common cancer among black South
      African males, and 60% of patients present with localized inoperable disease.
      Combined chemoradiotherapy has been reported to be superior to radiotherapy alone
      for localized inoperable esophageal cancer in North American patients. A study
      was carried out to determine if this was also applicable to South African
      patients, who present with more advanced disease. From September 1991 through
      June 1995, 70 patients with locally advanced (T3N0-1M0) squamous cancer of the
      esophagus were prospectively randomized to receive radiotherapy alone or
      radiotherapy combined with cisplatin and 5-fluorouracil. There was no
      statistically significant survival difference between the two groups. The median
      survival was 144 days in the group receiving radiotherapy alone, and 170 days in
      the group receiving radiotherapy combined with chemotherapy (p = 0.42). The
      degree of weight loss before initiation of therapy had a significant effect on
      survival regardless of the treatment arm. Radiotherapy in combination with
      chemotherapy, as administered in this study for South African patients with
      locally advanced, inoperable squamous cancer of the esophagus, is no better than
      radiotherapy alone.

PMID- 9781602
TI  - Evaluation of estramustine phosphate combined with weekly doxorubicin in patients
      with androgen-independent prostate cancer.
AB  - Thirty-one patients with progressive metastatic prostate cancer refractory to
      first- or second-line hormonal therapy were treated with a combination of daily
      oral estramustine phosphate (600 mg) and weekly intravenous doxorubicin (20
      mg/m2). Eighteen (58%) patients demonstrated a biologic response with a 50% or
      more serum prostate-specific antigen decline. The median duration of biologic
      response was three months. Five (45%) of the 11 patients with measurable lesions
      achieved a partial response in liver or retroperitoneal lymph nodes. The median
      duration of these objective responses was four months. Of 22 patients who
      required analgesics at the onset of the study, six (27%) achieved a significant
      reduction of pain. The combination of doxorubicin and estramustine phosphate was
      tolerated on an outpatient schedule. The occurrence of severe toxicities required
      suspension of therapy in six patients. At the end of the observation time, all
      patients but one had died, 29 of progressive prostatic cancer and one of
      toxicity. The median survival time from the onset of chemotherapy was 12 months.
      The administration of weekly doxorubicin with phosphate estramustine appears to
      be a safe combination for those patients with hormone-resistant prostate cancer
      who require chemotherapy. The benefit of chemotherapy should be investigated
      using relevant quality-of-life criteria in future trials.

PMID- 9781603
TI  - A phase II study of high-dose cimetidine and the combination 5-fluorouracil,
      interferon alpha-2A, and leucovorin in advanced renal cell adenocarcinoma.
AB  - Cimetidine is an H2-receptor antagonist used in the management of peptic ulcer
      disease and other hypersecretory gastrointestinal disorders. This agent has
      intriguing immunomodulatory characteristics. A phase II trial of cimetidine in 19
      patients with advanced malignant melanoma yielded an objective response rate of
      16%. Having demonstrated that cimetidine is active in malignant melanoma, the
      authors conducted a phase II trial of cimetidine, 800 mg twice daily by mouth, in
      patients with advanced renal cell cancer. Among the 31 eligible patients, only
      one (3.2%) achieved a regression. It was a partial regression lasting 93 days.
      Median time to treatment failure was 83 days. The combination of interferon alpha
      2A (IFL-RA) and 5-fluorouracil (5-FU) has been shown to be synergistic against
      experimental cell lines in vitro. Citrovorum factor (CF) added to 5-FU has been
      shown to improve objective tumor response compared with single-agent 5-FU in
      patients with advanced colorectal cancer. Fluorinated pyrimidines have shown some
      activity against renal cell cancer. We conducted a phase II trial of the
      combination of CF at 20 mg/m2 intravenous push followed by 5-FU at 325 mg/m2
      intravenously daily for 5 days every week with interferon alpha-2A 5 x 10(6)
      units/m2 subcutaneously on days 1, 3, 5 in patients with advanced renal cell
      cancer. Among the 31 eligible patients, only two (6.5%) achieved a regression.
      Both were partial regressions. Median time to treatment failure was 84 days.
      Neither regimen is recommended for further testing in patients with advanced
      renal cell adenocarcinoma.

PMID- 9781604
TI  - Severe esophageal toxicity after thoracic radiation therapy for lung cancer
      associated with the human immunodeficiency virus: a case report and review of the
      literature.
AB  - This case report documents severe esophagitis and rapid esophageal stricture
      formation in a man infected with the human immunodeficiency virus (HIV) who was
      treated with standard thoracic irradiation for locally advanced non-small-cell
      lung cancer. Severe late esophageal toxicity is a rare complication of radiation
      therapy in patients who are HIV negative, but those who are HIV positive may be
      at increased risk. This article reviews the literature suggesting that HIV
      infection may lead to unusually severe radiation-induced mucosal injury. High
      dose chest irradiation should be performed with caution in this group of
      patients.

PMID- 9781605
TI  - Docetaxel in head and neck cancer: a review.
AB  - Docetaxel has been shown to have significant antitumor activity. The mechanism of
      action is through stabilization of tubulin, arresting cells in the G2M phase of
      the cell cycle. The maximum tolerated dose of docetaxel is 100 mg/m2 every 21
      days. Short-lasting neutropenia is the dose-limiting toxicity. Other significant
      toxicities include alopecia, mucositis, fatigue, sensory neuropathy, fluid
      retention, rash, and hypersensitivity reactions. Phase II studies of docetaxel as
      a single agent in patients with squamous cell carcinoma of the head and neck
      (SCCHN) have documented response rates of 27% to 43%. Studies of docetaxel
      combined with cisplatin, and docetaxel, cisplatin, and 5-fluorouracil (TPF) as
      induction therapy for patients with SCCHN demonstrate that these regimens are
      highly active. An early trial of induction TPF with leucovorin (TPFL) has yielded
      an overall response rate of 100% and complete response rate of 61%. In vitro
      studies have shown docetaxel to be a potent radiation sensitizer for squamous
      cell carcinoma cell lines, and phase I trials using concurrent docetaxel and
      radiotherapy are ongoing.

PMID- 9781606
TI  - Preliminary result of phase II study of paclitaxel and cisplatin chemotherapy for
      advanced non-small-cell lung cancer in Chinese patients.
AB  - This phase II study was designed to assess the response rate and toxicity of
      paclitaxel and cisplatin chemotherapy in Chinese patients with untreated advanced
      non-small-cell lung cancer (NSCLC). Eligibility requirements included
      histologically confirmed stage IIIb-IV NSCLC, Eastern Cooperative Oncology Group
      performance status less than 2, no previous chemotherapy, and adequate bone
      marrow, renal, and hepatic function. From April 1996 through March 1997, 32
      patients were treated. The dose of paclitaxel was 135 mg/m2 as a 3-hour infusion
      on day 1 and cisplatin 75 mg/m2 on day 2. The regimen was repeated every 3 to 4
      weeks for up to 6 to 8 cycles unless there was evidence of tumor progression. The
      median age was 57 years (range, 31-77 years). Sixty-five percent were men. Sixty
      nine percent had adenocarcinoma, and 75% had stage IV disease. One hundred
      seventy-two cycles were administrated; 18 patients (56%) completed all six
      cycles. Peripheral neuropathy and myelosuppression were the principle toxicities.
      Neurotoxicity appeared to be dose limiting and manifested primarily as
      paresthesia. Grade 2 neurotoxicity was observed in 5% of courses, which was
      slowly reversible. However, the severity of myelosuppression was generally mild
      to moderate. No episode of neutropenic fever was noted. Thrombocytopenia remained
      infrequent throughout the study. Other nonhematologic toxicities were also
      generally mild. The objective response rate was 50%. In conclusion, this
      combination of paclitaxel and cisplatin is active in Chinese patients with
      advanced NSCLC. It merits further investigation in phase III trials.

PMID- 9781607
TI  - The combination of paclitaxel and carboplatin as first-line chemotherapy in
      patients with stage III and stage IV ovarian cancer: a phase I-II study.
AB  - The combination of paclitaxel 135 mg/m2 (24-hour infusion) and cisplatin 75 mg/m2
      is now considered the standard treatment in first-line chemotherapy for stage III
      suboptimally debulked and stage IV ovarian cancer. Interest is focused on the
      possibility of evaluating the combination of paclitaxel with carboplatin, because
      it was found to be less nefrotoxic and less neurotoxic than cisplatin. This study
      seeks to determine the maximum tolerated dose and to assess the antitumor
      activity of the combination of a 3-hour paclitaxel infusion followed by
      carboplatin. Thirty-three chemotherapy-naive patients with stage III-IV
      epithelial ovarian cancer entered this open, nonrandomized dose-finding study.
      The first dose level investigated was paclitaxel 125 mg/m2 and carboplatin 250
      mg/m2: the dose level progression was performed by alternatively increasing
      paclitaxel 25 mg/m2 and carboplatin 50 mg/m2. Cycles were repeated every 28 days.
      At least three patients were treated at each dose level. Overall, 233 and 224
      cycles, respectively, are evaluable for nonhematologic and hematologic toxicity.
      Dose-limiting toxicities (febrile neutropenia and severe fatigue) were observed
      in two of six patients at level VIII (paclitaxel 225 mg/m2 and carboplatin 400
      mg/m2) and therefore the previous dose-level (paclitaxel 200 mg/m2 and
      carboplatin 400 mg/m2) was considered as the maximum tolerated dose. Neutropenia
      (grade 3-4 in 63% of cycles), neurotoxicity (grade 2 in 37.5% and grade 3 in 9%
      of patients), arthromyalgias (grade 2 in 53% of patients and grade 3 in 3% of
      patients), and grade 3 alopecia were the most common toxicities observed. The
      incidence of thrombocytopenia was low (grade 3 in 4% of cycles) and no renal
      toxicity was observed. An objective remission was documented in 74% of 31
      evaluated patients, including eight complete remissions (26%) confirmed by second
      look surgery. The combination of paclitaxel 200 mg/m2 3-hour infusion followed by
      carboplatin 400 mg/m2 (30-minute infusion) is a safe and active regimen as first
      line chemotherapy for advanced ovarian cancer.

PMID- 9781608
TI  - Classic Kaposi sarcoma: experience at Rabin Medical Center in Israel.
AB  - Classic Kaposi sarcoma is an indolent cutaneous proliferative disease affecting
      mainly elderly people of Mediterranean and Jewish origin. The authors review the
      epidemiologic and clinical findings in Israeli patients with classic Kaposi
      sarcoma treated at the Institute of Oncology, Rabin Medical Center. A total of
      123 patients were identified. The average age at diagnosis was 68 years (range,
      20-90 years) and, as expected, there was a strong predominance of men (2.4:1).
      All but two patients were Jewish. The distribution of Ashkenazic Jews and
      Sephardic Jews was almost equal. Twenty-three patients (19%) had secondary
      malignancies that were mostly solid tumors. The clinical course was indolent and
      rarely fatal (4% disease-related mortality). Multivariate analysis revealed that
      non-Ashkenazic origin, age over 70 years, multiple lesions (>10), and
      immunocompromised conditions adversely affected survival. Radiotherapy for
      localized skin lesions yielded an 88% objective response, with symptomatic relief
      in 95% of patients. Chemotherapy was similarly effective (76% response rate) in
      patients with disseminated disease. These data demonstrate the indolent nature of
      classic Kaposi sarcoma which usually requires a less aggressive therapeutic
      approach than in the African and AIDS-related types of Kaposi sarcoma.

PMID- 9781609
TI  - Extended survival in 80 patients with operable, locoregionally recurrent breast
      cancer treated with chemotherapy.
AB  - Locoregional recurrence is a harbinger of disseminated disease, and historically
      the estimated 5-year survival when treated with local therapy only varies between
      21% and 37%. The role of systemic treatment after local treatment is unclear at
      present. The authors investigated the results of systemic chemotherapy for these
      patients after complete local surgical resection. Data on 80 patients were
      evaluable for toxicity, time to treatment failure (TTF), and survival. Sixty-four
      patients received doxorubicin-based treatments, four received methotrexate-based
      combinations, and 12 received tamoxifen only. Among the 68 patients treated with
      cytostatics, there were two possible treatment-related deaths. Two patients
      developed grade 3 neutropenia, four developed grade 3 vomiting, and 42 had grade
      2 toxicity. The 2- and 5-year disease free survival at a mean follow-up period of
      5.5 years were 56% and 38%, respectively. The projected median TTF was 32 months
      (95% confidence interval, 23-82). Two- and 5-year overall survival were 86% and
      62%, respectively, with a projected median survival of 93 months (7.75 years; 95%
      confidence interval, 64-177). These results show systemic therapy improved TTF
      and survival for patients with stage IV, no-evidence-of-disease breast cancer.
      Randomized studies are needed to confirm these findings and define optimal
      therapy.

PMID- 9781610
TI  - Treatment of non-small-cell lung cancer with prolonged oral etoposide.
AB  - The efficacy and toxicity of chronic administration of oral etoposide was
      evaluated in 61 patients with inoperable non-small-cell lung cancer (NSCLC). Ten
      patients received previous chemotherapy, 15 received radiotherapy, and one
      received both treatments. Twenty-four patients had concurrent cardiac and/or
      pulmonary impairment, which precluded more intensive treatment. Etoposide was
      given orally, 100 mg daily for 7 consecutive days and consequently 100 mg every
      other day for 14 more days in a 28-day schedule. Partial response was observed in
      17 patients (28%; 95% confidence interval, 17-39%) and stable disease in 21
      (34%). The median duration of response was 6 months (range, 2-34 months). The
      median survival for responders was 22 months and that of nonresponders was 7
      months (p < 0.001). The median survival for all patients was 9 months (range, 1
      35 months; 95% confidence interval, 5.69-12.31%). Toxicity was acceptable. Other
      than alopecia, which was observed in all patients, myelotoxicity was the most
      common toxicity--particularly leukopenia, which was severe in nine patients.
      Other less common toxicities included nausea and vomiting, stomatitis, anorexia,
      and neurotoxicity and were mild. No treatment-related deaths were observed. In
      conclusion, the regimen was effective and well tolerated with significant
      survival benefit for the responders. It represents an interesting therapeutic
      approach, especially in the elderly.

PMID- 9781611
TI  - Epirubicin has modest single-agent activity in head and neck cancer but limited
      activity in metastatic melanoma and colorectal cancer: phase II studies by the
      Eastern Cooperative Oncology Group.
AB  - Epirubicin (4'-epidoxorubicin), a diastereoisomer of doxorubicin, has established
      activity in the treatment of many cancer types sensitive to doxorubicin. Its
      activity in other tumor targets such as melanoma, head and neck cancer, and
      recurrent colorectal cancer has been less well defined. Three concurrent phase II
      studies examined the efficacy and toxicity of epirubicin (90 mg/m2 given
      intravenously at 3-week intervals) in the treatment of 71 patients with the
      aforementioned cancers. Of 66 eligible patients who were assessable for response,
      one patient (with colorectal cancer) achieved a complete response and three
      patients (with head and neck cancer) achieved partial responses. The response
      rate in patients with head and neck cancer was 18% (95% confidence interval, 4
      43%). Myelosuppression, alopecia, and nausea were the most frequent toxicities.
      Two patients died of neutropenic sepsis and grade IV leukopenia occurred in six
      patients (8%). Grade III toxicities were as follows: leukopenia (17%), anemia
      (10%), alopecia (8%), fever (1%), thrombocytopenia (1%). Grade I or II cardiac
      toxicity was noted in four patients at cumulative doses ranging between 375 mg/m2
      to 1,283 mg/m2. Epirubicin is ineffective as a single agent at this dose and
      schedule in the treatment of patients with melanoma and colorectal cancer. In
      head and neck cancer, a modest response rate encourages further exploration of
      epirubicin and related anthracyclines in combination regimens.

PMID- 9781612
TI  - Retinoid-induced hypercalcemia in a patient with kaposi sarcoma associated with
      acquired immunodeficiency syndrome.
AB  - Retinoids are commonly used for the treatment of nonmalignant skin disorders and
      occasionally for the treatment of various neoplasms including epidemic Kaposi
      sarcoma (KS). Dry skin and mucus membranes, muscle and joint aches, alopecia,
      headaches, and liver and lipid abnormalities are the most frequent medication
      related side effects. Very rarely, this class of drugs is associated with the
      development of hypercalcemia. The authors report the case of a man with acquired
      immunodeficiency syndrome (AIDS)-associated KS who, while participating in a
      phase II clinical trial of LGD 1057 (9-cis-retinoic acid) for treatment of
      epidemic KS, developed hypercalcemia, mental status changes, and renal
      insufficiency. The etiologic factors of retinoid-induced hypercalcemia are
      imperfectly understood, but with drug withdrawal his serum calcium, mental
      acuity, and renal function quickly normalized. Hypercalcemia occurs infrequently
      in the setting of AIDS and when present, is usually mediated by opportunistic
      infections. Clinicians should be alert to this potentially life-threatening
      iatrogenic complication that responds favorably to drug withdrawal.

PMID- 9781613
TI  - Cisplatin, ifosfamide, and vinorelbine combination chemotherapy in stage III-IV
      non-small-cell lung cancer: a phase II study.
AB  - The authors evaluate the combination of three drugs, vinorelbine, ifosfamide, and
      cisplatin, which have been shown to produce good response rates and a significant
      gain in survival when any two of them are given together. Seventy-seven untreated
      patients with inoperable stage III-IV non-small-cell lung cancer from three
      centers were included. The combination consisted of cisplatin 30 mg/m2 daily,
      ifosfamide 1,500 mg/m2 daily, mesna 1,500 mg/m2 daily on days 1-3, and
      vinorelbine 25 mg/m2 daily on days 1 and 8. Four cycles were administered every 4
      weeks for a total of 267 cycles, before an assessment for toxicity, effective
      dose intensity, response rate, and survival was made. Toxicity was mainly
      hematologic (grade 3-4 neutropenia (15.7%), anemia (8.2%), and thrombopenia
      (2.6%)) but did not require granulocyte colony-stimulating factors. Objective
      response rate was 41.1% (95% confidence interval, 29.5-52.9%) in 68 patients
      suitable for assessment. The mean time to progression and median survival were
      7.7 +/- 1.3 months and 11.6 months, respectively. One-year survival was 47.1%.
      The effective dose intensity of cisplatin and ifosfamide correlated strongly with
      survival, whereas stage and performance status did not. This study confirms
      previously reported favorable results for response and survival rates obtained in
      stage III-IV non-small-cell lung cancer with the vinorelbine, ifosfamide, and
      cisplatin combination. Respect of a scheduled dose intensity has a clear-cut
      influence on survival and should be evaluated routinely in future
      polychemotherapy trials.

PMID- 9781614
TI  - Sequential treatment including high-dose chemotherapy with peripheral blood stem
      cell support in patients with high-risk stage II-III breast cancer: outpatient
      administration in community cancer centers.
AB  - The authors determined outcomes for patients with localized high-risk breast
      cancer undergoing sequential outpatient treatment with conventional-dose adjuvant
      therapy, chemotherapy, and growth factor mobilization of peripheral blood stem
      cells (PBSC) and high-dose chemotherapy (HDC) with PBSC support in community
      cancer centers. Ninety-six patients with stage II-IIIB noninflammatory breast
      cancer with 10 or more positive lymph nodes and a median age of 46 years (range,
      22-60 years) were treated with: 1) doxorubicin, 5-fluorouracil, and methotrexate
      (AFM), four courses at 2-week intervals; 2) cyclophosphamide (4 g/m2) and
      etoposide (600 mg/m2) (CE), followed by filgrastim (6 microg/kg per day) and PBSC
      harvest; and 3) cyclophosphamide (6 g/m2), thiotepa (500 mg/m2), and carboplatin
      (800 mg/m2) (CTCb), followed by PBSC infusion. All 96 patients received AFM, 95
      (99%) received CE, and 95 (99%) received CTCb with a median hospital stay of 12
      days (5-34 days) for all phases of treatment. Sixty-nine patients (72%) are
      alive, 55 (57%) without relapse at a median follow-up of 53 months (range, 37-77
      months). One patient (1%) died of acute myeloid leukemia and all other deaths
      were associated with recurrent breast cancer. The probabilities of event-free
      survival (EFS) at 4 years for patients with or without locally advanced disease
      were 0.37 and 0.69, respectively (p = 0.004), and 0.71 and 0.48 for patients who
      were estrogen/progesterone receptor (ER/PR) positive or ER/PR negative,
      respectively (p = 0.016). In multivariate analyses, locally advanced disease
      (relative risk, 2.3; p = 0.021) and ER/PR-negative hormone receptor status
      (relative risk, 2.2; p = 0.014) were the only adverse risk factors for EFS
      identified. Patients with zero, one, or two of these adverse risk factors had 4
      year EFS of 0.80, 0.56, and 0.33, respectively. The sequential administration of
      AFM, CE, and CTCb followed by PBSC in an outpatient community setting was well
      tolerated in patients with high-risk stage II-III breast cancer. More intensive
      or more novel treatment strategies will be required to decrease relapses in
      patients who have ER/PR-negative tumors and/or have locally advanced disease.

PMID- 9781615
TI  - Carcinoma of the pancreas presenting as an orbital tumor: a case report.
AB  - Metastasis to the orbit from pancreatic adenocarcinoma is rare. A 38-year-old man
      with metastatic adenocarcinoma of the right orbit at initial examination is
      described. Two months later he was diagnosed with a pancreatic primary tumor. The
      incidence and pattern of orbital metastasis in carcinomas is briefly discussed.

PMID- 9781616
TI  - Impaired vagus nerve-mediated control of insulin secretion in Wistar fatty rats.
AB  - It has been reported that hyperglycemia in the portal venous blood suppresses
      afferent activity of the hepatic branch of the vagus nerve, which in turn
      accelerates efferent activity of the pancreatic branch of the vagus nerve to
      stimulate insulin secretion. The present study examined this neural control
      mechanism in genetically obese diabetic male Wistar fatty (fa/fa) rats. Adult
      (aged 12 to 14 weeks) Wistar fatty rats were obese, hyperinsulinemic, and
      hyperglycemic. Young (aged 5 to 6 weeks) Wistar fatty rats were slightly obese
      and hyperinsulinemic, but were euglycemic compared with the lean littermates. In
      both adult and young lean littermates, the plasma insulin response after an
      intragastric glucose load (1 g/kg) was diminished by intracerebroventricular
      (i.c.v.) atropine methylbromide (methylatropine 10 nmol) pretreatment, and a
      transient increase in plasma insulin was observed after selective hepatic
      vagotomy, as reported in normal rats. In contrast, in both adult and young Wistar
      fatty rats, the plasma insulin response after an intragastric glucose load was
      not diminished by i.c.v. methylatropine pretreatment, and plasma insulin
      decreased slightly after selective hepatic vagotomy. Further, afferent discharges
      of the hepatic vagal branch decreased and efferent discharges of the
      celiac/pancreatic vagal branch increased when 10 mg glucose was infused into the
      portal vein in the 9-week-old lean littermates, as reported in normal rats. In 7
      week-old Wistar fatty rats, afferent discharges of the hepatic vagal branch
      decreased but efferent discharges of the celiac/pancreatic vagal branch did not
      increase after intraportal glucose infusion. It is concluded that the vagus nerve
      mediated regulation of insulin secretion is impaired from an early stage of life
      in Wistar fatty rats. Efferent discharges of the vagus nerve to the pancreas seem
      not to be suppressed by afferent discharges from the hepatic vagus branch, which
      may lead to insufficient insulin secretion in response to nutrient ingestion
      followed by a delayed peak. These abnormalities may thus lead to the insulin
      resistance and fasting hyperinsulinemia that characterize the Wistar fatty rat
      model.

PMID- 9781618
TI  - Alcohol-related diols cause acute insulin resistance in vivo.
AB  - Epidemiological studies suggest that alcohol consumption is an independent risk
      factor for the development of non-insulin-dependent diabetes mellitus (NIDDM).
      Alcoholism is known to be associated with increased plasma levels of two novel
      diols, 2,3-butanediol and 1,2-propanediol, metabolites known to impair insulin
      action in isolated adipocytes. This study examines whether 2,3-butanediol and 1,2
      propanediol have the capacity to impair insulin action acutely in vivo in the
      rat. Using the euglycemic-hyperinsulinemic clamp, it is shown that the two diols
      reduce whole-body glucose utilization (by approximately 30%), with the onset of
      insulin resistance in vivo occurring at plasma concentrations of 2,3-butanediol
      (33 micromol/L) at least one order of magnitude (P < .001) lower than 1,2
      propanediol (432 micromol/L). Tracer methodologies using [U-14C]glucose and 2
      deoxy[1-(3)H]glucose indicate that the reduction in whole-body glucose
      utilization is accompanied by a reduction in glucose uptake and glycogen
      synthesis in the skeletal muscle and heart. The association between elevated
      plasma diol levels and insulin resistance demonstrated in this report raises the
      question of whether there is a link between the high plasma diol levels in
      alcohol abusers and their increased susceptibility to NIDDM.

PMID- 9781619
TI  - Endocrine and metabolic aberrations in men with abdominal obesity in relation to
      anxio-depressive infirmity.
AB  - Abdominal obesity, anxiety, and depression have been found to cluster in several
      studies. To further characterize these associations, the following study was
      performed. In a population of 51-year-old men (N = 284), measurements of obesity
      (body mass index [BMI]) and body fat distribution (waist to hip ratio [WHR] and
      sagittal trunk recumbent diameter [D]) were analyzed in relation to dexamethasone
      (0.5 mg) inhibition of cortisol secretion, measured as salivary cortisol.
      Symptoms of anxiety and depression were defined by a validated questionnaire.
      Furthermore, testosterone, insulin-like growth factor-I (IGF-I), insulin,
      glucose, and serum lipid levels were measured. Twenty-five men (8.8%) had
      symptoms of anxiety and depression. BMI, WHR, and D correlated negatively with
      testosterone, except for BMI in the anxio-depressive (ADP) group. IGF-I showed no
      significant relationship. Furthermore, fasting insulin and the insulin to glucose
      ratio correlated positively and high-density lipoprotein (HDL) cholesterol
      correlated negatively with BMI, WHR, and D in the total study population and in
      the subgroups. Total and low-density lipoprotein (LDL) cholesterol showed no
      significant relationships. Correlation coefficients tended to be higher in ADP
      men. Dexamethasone inhibition showed a negative significant relationship with BMI
      (rho = -.47, P = .025), WHR (borderline, rho = -.37, P = .086), and D (rho = 
      .43, P = .046) only in the ADP group. Comparing the ADP group versus the group
      without anxio-depression (ADO) and high or low BMI (P = .008), WHR (P = .026),
      and D (P = .012) showed blunted dexamethasone inhibition only in ADP men with
      high anthropometric measurements. These findings suggest there is a subgroup with
      elevated BMI, WHR, and D in whom a blunted dexamethasone response is found
      associated with traits of anxiety and depression, conditions characterized by
      such an abnormality. The reason for the association might be insufficient control
      of cortisol secretion, followed by visceral fat accumulation.

PMID- 9781617
TI  - Relationships between insulin resistance and lipoproteins in nondiabetic African
      Americans, Hispanics, and non-Hispanic whites: the Insulin Resistance
      Atherosclerosis Study.
AB  - The study purpose was to explore the association between dyslipidemia and insulin
      resistance in three ethnic groups. The Insulin Resistance Atherosclerosis Study
      (IRAS) is a multicenter epidemiologic study conducted at four clinical centers in
      California, Texas, and Colorado. The study population for this analysis consisted
      of 931 non-Hispanic white, African American, and Hispanic men and women (aged 45
      to 64 years) without diabetes. The IRAS clinical examinations included
      lipoprotein measures, a 75-g glucose tolerance test, and the frequently sampled
      intravenous glucose tolerance (FSIGT) test. The results show a consistent
      relationship between insulin-mediated glucose disposal and dyslipidemia in
      African American, Hispanic, and non-Hispanic white men and women. Further, LDL
      size was inversely associated with insulin resistance in all three ethnic groups.
      These findings indicate that dyslipidemia is a fundamental part of the insulin
      resistance syndrome in all of the ethnic groups studied.

PMID- 9781620
TI  - Impaired Na+,K+ATPase activity in red blood cells in euthyroid women treated with
      levothyroxine after total thyroidectomy for Graves' disease.
AB  - In patients suffering from hyperthyroidism dependent on Graves' disease, a
      reduction in Na+,K+ATPase activity has been demonstrated in red blood cells
      (RBCs), as well as an inverse correlation between this enzymatic action and free
      triiodothyronine (FT3) levels. The restoration of normal FT3 values also brings
      about a normalization of Na+,K+ATPase activity in erythrocytes. These results
      have made it possible to hypothesize that the thyroid hormones control
      Na+,K+ATPase activity and that this control is manifested by means of variations
      in the number of ouabain-binding sites. For this reason, the measurement of the
      activity of the Na/K pump can be considered as a further indicator of the
      peripheral effects of thyroid hormones. With a view to assess the relation
      between the course of treated hyperthyroidism and Na+,K+ATPase activity during
      antithyroid therapy and after surgical thyroidectomy followed by replacement
      therapy, we studied 24 patients affected by Graves' disease (group Graves [GG]).
      They were compared with 24 female Graves' patients who underwent total
      thyroidectomy for nontoxic and diffuse nodular goiter (NDNG) (group control [GC])
      and with 24 normal healthy women (group normal [GN]). When Graves'
      hyperthyroidism was diagnosed, the Na+,K+ATPase activity in RBCs was impaired in
      all GG patients. Thionamide treatment restored the normal activity of the Na/K
      pump, accompanied by normalization of the number of ouabain-binding sites. One
      hundred eighty days after thyroidectomy, in conditions of clinical and
      biochemical euthyroidism due to replacement therapy with levothyroxine, the
      activity of Na+,K+ATPase in RBCs was once again reduced in GG, while appearing
      normal in GC and GN (1.77 +/- 0.16 mmol Pi h(-1) L(-1) RBCs v 2.09 +/- 0.26 v
      2.09 +/- 0.24, P < .05). Different instrumental or biochemical parameters, such
      as glycemia, serum lipids, ions, serum alkaline phosphatase (AIPh), serum
      creatine phosphokinase (CPK), blood pressure, and heart rate, were evaluated and
      appeared normalized in GG and GC 180 days after surgery. We conclude that (1) in
      patients suffering from Graves' disease, subjected to total thyroidectomy
      followed by levothyroxine replacement therapy, there is a reduction in the
      activity of the Na+,K+ATPase on erythrocytes 6 months after the surgical
      approach; and (2) a similar alteration is not observed in patients subjected to
      thyroidectomy for NDNG. These findings allow the formulation of the hypothesis
      that (1) treatment with levothyroxine for 180 days after thyroidectomy in GG is
      not long enough to restore the normality of all the peripheral indicators of
      action of the thyroid hormones; and (2) levothyroxine replacement therapy is
      unable to guarantee euthyroidism in all the tissues in GG (eg, during
      hematopoiesis in the bone marrow).

PMID- 9781621
TI  - Long-term effects of perindopril on metabolic parameters and the heart in the
      spontaneously hypertensive/NIH-corpulent rat with non-insulin-dependent diabetes
      mellitus and hypertension.
AB  - The spontaneously hypertensive/NIH-corpulent (SHR/N-cp) rat is a genetic model
      that exhibits both non-insulin-dependent diabetes mellitus (NIDDM) and
      hypertension. To determine the impact of long-term treatment with the long-acting
      angiotensin-converting enzyme (ACE) inhibitor perindopril (PE) on the glucose
      metabolism, lipid levels, and heart in this model, studies were performed in
      three groups of SHR/N-cp rats maintained on a diet containing 54% carbohydrate
      with 18% sucrose and 36% starch. One group of obese rats received PE (0.5 to 1.0
      mg/kg body weight/d) for 3 to 4 months, a second group of obese rats received no
      treatment, and a third group of lean rats were used as controls. The mean
      systolic blood pressure (SBP) increased gradually in both untreated obese and
      lean rats, with lean animals showing slightly higher levels compared with
      untreated obese rats. By contrast, SBP was reduced to normal levels in PE-treated
      obese rats throughout the treatment period. Compared with lean rats, obese rats
      showed significantly higher body weight and fasting serum levels of glucose,
      insulin, total cholesterol (TC), and triglyceride (TG). However, no significant
      differences were observed in these metabolic parameters between PE-treated and
      untreated obese rats. Plasma renin activity measured at the end of the treatment
      period was significantly higher in PE-treated rats compared with untreated obese
      and untreated lean rats. The mean heart weight and left ventricular weight,
      expressed in absolute terms or indexed to body weight, were significantly lower
      in PE-treated versus untreated obese and untreated lean rats. To further
      determine whether glucose metabolism is directly affected by PE treatment, in
      vitro glycogen synthesis was evaluated in isolated soleus muscles obtained from
      three additional groups of animals. The basal rate of muscle glycogen synthesis
      was significantly lower in obese compared with lean rats (P < .05), but did not
      differ between PE-treated and untreated obese rats. Maximal insulin-stimulated
      glycogen synthesis increased threefold in PE-treated obese rats, but this
      increase did not differ from the increases observed in untreated obese and lean
      rats. In conclusion, the present study shows that long-term PE treatment in obese
      SHR/N-cp rats with NIDDM and hypertension effectively controlled systemic
      arterial pressure and resulted in a significant reduction in left ventricular
      weight. However, these favorable effects of PE were not associated with
      significant improvement in glucose tolerance, hyperinsulinemia, and
      hyperlipidemia in this model. PE also had no direct stimulatory effects on either
      basal or insulin-mediated glycogen synthesis in the isolated soleus muscle of
      obese rats, perhaps because of the severe insulin-resistant state of the animals.
      Our results support the clinical observations that antihypertensive therapy with
      ACE inhibitors has neutral effects on glucose metabolism and insulin sensitivity
      in patients with combined hypertension and NIDDM.

PMID- 9781622
TI  - Metabolic and immune parameters at clinical onset of insulin-dependent diabetes:
      a population-based study. IMDIAB Study Group. Immunotherapy Diabetes.
AB  - The age at diagnosis of insulin-dependent diabetes mellitus (type I DM) varies
      between childhood and adulthood. The aim of this study was to define the
      immunologic and metabolic characteristics of the disease according to the age at
      which it is diagnosed. We evaluated the residual beta-cell function (basal and
      stimulated C-peptide) and frequency of two major islet cell-related
      autoantibodies, glutamic acid decarboxylase (GAD) and tyrosine phosphatase-like
      molecule (IA-2ic), at the onset of type I DM. A population-based study was
      performed with 235 consecutive cases of recent-onset (<4 weeks) type I DM (ages 5
      to 45 years) diagnosed in the Lazio region of central Italy. Five age groups were
      considered: patients diagnosed between ages 5 and 7 years (n = 10), 7 and 10
      years (n = 38), 10 and 17 years (n = 94), 17 and 20 years (n = 17), and 20 and 45
      years (n = 76). Patients diagnosed before puberty had significantly reduced C
      peptide secretion compared with patients diagnosed at a later age (P < .02).
      Glycosylated hemoglobin (HbA1c) did not differ at diagnosis between the different
      age groups. Patients diagnosed at puberty or after required significantly less
      insulin compared with younger patients (P < .04). GAD antibodies were found in
      65% and IA-2ic antibodies in 59% of patients. GAD antibodies tended to be more
      frequent in patients diagnosed after age 17 compared with younger patients (P =
      .05), while IA-2ic antibodies were not age-related. These data suggest that (1)
      the extent of beta-cell damage differs between patients diagnosed before and
      after puberty, the process being more destructive in children less than 7 years
      of age, when C-peptide levels are the lowest; and (2) residual beta-cell function
      at diagnosis is not influenced by the presence or absence of islet cell-related
      antibodies. These findings have implications for trials in type I DM diagnosis
      aimed at protecting beta cells from end-stage destruction and in attempts to
      prevent the disease in susceptible individuals.

PMID- 9781623
TI  - Effects of methanol extract of Chansu on hypothalamic-pituitary-testis function
      in rats.
AB  - Chansu, a galenical preparation of the dried white venom of Chinese Bufo bufo
      gargarizans, is one of the major components of Kyushin, a traditional Chinese
      medicine. Kyushin is reported to have a cardiotonic effect that has been
      suggested to be due to the action of bufadienolides such as bufalin and
      cinobufagin. Recently, we found that administration of bufalin in male rats
      diminished the luteinizing hormone (LH) response to gonadotropin-releasing
      hormone (GnRH) and the secretion of testosterone both in vivo and in vitro. These
      observations suggest that Chansu may possess hypogonadal effects in male rats. In
      the present study, the effects of the methanol extract of Chansu on hypothalamic
      pituitary-testicular function in male rats were examined. Crude Chansu was
      extracted by methanol and purified by a Sep-Pak C18 column. No activity of
      bufalin, cinobufagin, estradiol, or digoxin in purified methanol extract was
      detected; all Chansu used in this study was the purified methanol extract. A
      single intravenous injection of Chansu resulted in a decrease of the basal (20%
      to 55%) and human chorionic gonadotropin (hCG)-induced (35% to 40%) levels of
      plasma testosterone and the GnRH-induced level of plasma LH (25% to 30%).
      Administration of Chansu in vitro decreased basal and hCG-stimulated testosterone
      production by 60% to 70% and 40% to 60%, respectively, as well as spontaneous and
      forskolin- or 3-isobutyl-1-methylxanthine (IBMX)-induced accumulation of
      adenosine 3',5'-cyclic monophosphate (cAMP) by 30% to 45% in rat testicular
      interstitial cells. Although LH release by rat anterior pituitary glands was
      diminished, GnRH release by the rat mediobasal hypothalamus was enhanced by
      administration of Chansu in vitro. These results suggest that the bufalin-free
      extracts of Chansu inhibit testosterone secretion in rats, in part, due to (1) a
      decreased production of testicular cAMP, (2) a decreased response of testosterone
      to gonadotropin, and (3) a reduction of the LH response to GnRH.

PMID- 9781624
TI  - Glucose contribution to in vivo synthesis of glyceride-glycerol and fatty acids
      in rats adapted to a high-protein, carbohydrate-free diet.
AB  - Triacylglycerol (TAG) synthesis from all carbon sources and from glucose carbon
      was evaluated in rats fed a high-protein, carbohydrate-free (HP) diet or control
      diet by determining simultaneously in the same animal the rate of incorporation
      of 3H2O and of 14C-glucose into the two TAG moieties in the carcass, liver, and
      retroperitoneal and epididymal adipose tissue. Incorporation rates of 3H2O into
      TAG-fatty acids (FAs) in the two adipose tissues and in liver were reduced in HP
      rats to about 20% and 50%, respectively, of the rates in control rats. In the two
      experimental groups, glucose was a poor precursor for FA synthesis, contributing
      only 22.8% of whole-body (carcass plus liver) total FA synthesis in control rats
      and even less (14%) in HP rats. In contrast to the reduction in FA synthesis,
      incorporation of 3H2O into TAG-glycerol in HP rats did not differ significantly
      or was even higher (in epididymal tissue) versus the control level. In all
      tissues of both HP and control rats, the rate of 14C-glucose incorporation into
      TAG-glycerol was much higher than the rate of incorporation into FA.
      Glyceroneogenesis, estimated by subtracting TAG-glycerol synthesis from glucose
      from the rate obtained with 3H2O, was significantly increased in adipose tissue
      from HP rats, with almost all of the glycerol formed by this route being used to
      esterify preformed FAs. It is suggested that the increased adipose tissue
      glyceroneogenesis is important for esterification of diet-derived FA and
      preservation of body fat stores in rats adapted to the HP diet.

PMID- 9781625
TI  - Effects of oral combined hormone replacement therapy on plasma lipids and
      lipoproteins.
AB  - Hormone replacement therapy has been shown to decrease the risk of coronary heart
      disease (CHD) in menopausal women. In this cross-sectional study, we addressed
      the following question: What effects would combined oral hormone replacement
      therapy have on plasma lipid and lipoprotein profiles independent of the other
      known CHD risk factors? We analyzed the plasma lipoproteins of two groups of
      menopausal women who were randomly selected from a large database of individuals.
      One group (n = 10) was not taking any hormone replacement therapy (NO HRT), while
      the second group (n = 8) was taking a daily dose of 0.625 mg conjugated estrogen
      and 2.5 mg medroxyprogesterone orally (PremPro, Wyeth-Ayerst, Philadelphia, PA)
      for at least 6 months (HRT). The two groups were not different in age, body
      weight, percent body fat, body mass index (BMI), waist to hip ratio, blood
      pressure, or insulin and glucose levels. High-density lipoprotein (HDL)
      cholesterol was significantly higher (P < .05) in the HRT group. The total
      cholesterol (TC) to HDL-cholesterol ratio was significantly lower for HRT versus
      NO HRT (P < .05). Apolipoprotein (apo) A-1, the apo A-1/B ratio, and
      lecithin:cholesterol acyltransferase (LCAT) activity were significantly higher in
      HRT (P < .05). Lipoprotein subclass profiles measured by nuclear magnetic
      resonance (NMR) spectroscopy showed an increase in larger HDL subpopulations (H3
      and H4) in HRT (P < .05), which are considered antiatherogenic. No differences
      were seen in the cholesterol concentration or size of low-density lipoprotein
      (LDL) subpopulations in HRT compared with NO HRT. These results indicate that the
      combined estrogen and progesterone treatment leads to beneficial effects on
      plasma lipoproteins. The beneficial effects include (1) increases in HDL
      cholesterol and predominance of HDL2, (2) no adverse effects on LDL subpopulation
      distribution, and (3) increases in apo A-1 levels and LCAT activity, which
      indicate an improvement in reverse cholesterol transport.

PMID- 9781627
TI  - Metabolism of cystathionine, N-monoacetylcystathionine, perhydro-1,4-thiazepine
      3,5-dicarboxylic acid, and cystathionine ketimine in the liver and kidney of D,L
      propargylglycine-treated rats.
AB  - Experimental cystathioninuria was induced by injection of D,L-propargylglycine in
      rats. The novel cystathionine metabolites, N-monoacetylcystathionine (NAc-cysta),
      perhydro-1,4-thiazepine-3,5-dicarboxylic acid (PHTZDC), and cystathionine
      ketimine (CK), were identified previously in the urine of patients with
      cystathioninuria and D,L-propargylglycine-treated rats. In this study, we
      identified these compounds in the liver and kidney of D,L-propargylglycine
      treated rats using liquid chromatography-mass spectrometry with an atmospheric
      pressure chemical ionization interface system (LC/APCI-MS) and an amino acid
      analyzer. The metabolism of these compounds in the liver and kidney of D,L
      propargylglycine-treated rats was also studied. PHTZDC, NAc-cysta, and CK were
      accumulated in the rat tissues in proportion to the content of cystathionine
      after D,L-propargylglycine administration. The concentrations of these compounds
      in the liver were higher than those in the kidney, and these compounds reached
      maxima earlier in the liver than in the kidney.

PMID- 9781626
TI  - Effects of glucagon on renal and hepatic glutamine gluconeogenesis in normal
      postabsorptive humans.
AB  - Glutamine is an important gluconeogenic amino acid in postabsorptive humans. To
      assess the effect of glucagon on renal and hepatic glutamine gluconeogenesis, we
      infused six normal healthy postabsorptive subjects with glucagon at a rate chosen
      to produce circulating glucagon concentrations found during hypoglycemia and,
      using a combination of isotopic and net balance techniques, determined the
      systemic, renal, and hepatic glucose release and renal and hepatic production of
      glucose from glutamine. Infusion of glucagon increased systemic and hepatic
      glucose release (both P < .02), but had no effect on renal glucose release (P =
      .26). Systemic and hepatic glutamine gluconeogenesis increased from 0.45 +/- 0.3
      and 0.11 +/- 0.02 micromol x kg(-1) x min(-1), respectively, to 0.61 +/- 0.04 (P
      = .002) and 0.31 +/- 0.03 micromol x kg(-1) x min(-1) (P = .001), respectively,
      whereas renal glutamine gluconeogenesis was unchanged (from 0.33 +/- 0.03 to 0.30
      +/- 0.04 micromol x kg(-1) x min(-1), P = .20). The hepatic contribution to
      systemic glutamine gluconeogenesis increased from 25.2% +/- 6.2% to 51.6% +/-
      5.5% (P = .002), while that of the kidney decreased from 74.8% +/- 6.2% to 48.4%
      +/- 5.5% (P = .003). Glucagon had no effect on the renal net balance, fractional
      extraction, or uptake and release of either glucose or glutamine. We thus
      conclude that glucagon stimulates glutamine gluconeogenesis in normal
      postabsorptive humans, predominantly due to an increase in hepatic glutamine
      conversion to glucose. Thus, under certain conditions such as counterregulation
      of hypoglycemia, the liver may be an important site of glutamine gluconeogenesis.

PMID- 9781628
TI  - The contribution of glucose to neonatal glucose homeostasis in the lamb.
AB  - A multiplicity of substrates and hormones interact to influence neonatal glucose
      homeostasis. Based on prior studies in our laboratory, we hypothesized that
      glucose alone does not tightly control neonatal glucose homeostasis. Fifteen
      spontaneously delivered, mixed-breed term lambs, weighing 4.7 +/- 0.9 kg (mean +/
      SD) were studied at 4.7 +/- 0.6 days after birth following administration of 100
      microCi D[6,6-(3)H2] glucose in 0.9% NaCl by the prime plus constant infusion
      technique to measure glucose production. After a baseline period, five lambs
      received 8.5 mg x kg(-1) x min(-1) glucose in combination with the following to
      isolate the contribution of glucose: somatostatin to block insulin, glucagon, and
      growth hormone release; metyrapone to block cortisol release; phentolamine to
      block alpha-adrenergic release; and propranolol to block beta-adrenergic release
      (glucose + blockade). Five lambs received the above without the glucose infusion
      (blockade). Five lambs continued to receive 0.9% NaCl alone as the diluent for
      the isotopic tracer throughout the study (control). The glucose + blockade group
      had a significant increase in plasma glucose (P < .0001) and a significant
      increase in total glucose appearance (P < .0001) compared with both the blockade
      and control groups. Under conditions of glucose infusion at a rate 49% greater
      than the basal rate, the endogenous glucose production rate persisted such that
      there was only an evanescent decrease compared with that of the control group,
      which was not statistically different over time. As a substrate, glucose does not
      tightly control neonatal glucose homeostasis.

PMID- 9781629
TI  - Insulin sensitivity in women at risk of coronary heart disease and the effect of
      a low glycemic diet.
AB  - The risk of coronary heart disease (CHD) is influenced by family history, insulin
      sensitivity (IS), and diet. Adiposity affects CHD and IS. The cellular mechanism
      of IS is thought to involve the adipocyte cytokine tumor necrosis factor-alpha
      (TNF-alpha). Insulin-stimulated glucose uptake in isolated subcutaneous and
      omental adipocytes obtained during elective surgery was measured in 61
      premenopausal women, 24 with a parental history (PH) of CHD. In vivo IS was
      measured using the short insulin tolerance test (SITT) in 28 women, 16 with PH
      CHD, before and 3 weeks after randomization to a low glycemic index (LGI) or high
      glycemic index (HGI) diet. In vitro adipocyte IS and TNF-alpha production was
      measured following dietary modification. On the habitual diet, in vitro insulin
      stimulated glucose uptake in adipocytes as a percentage increase over basal was
      less in women with PH-CHD than in those without it (presented as the median with
      95% confidence limits: subcutaneous, 28% (17% to 39%) v 96% (70% to 120%), P <
      .01); omental, 40% (28% to 52%) v 113% (83% to 143%), P < .01). In vivo IS in 16
      PH-CHD subjects and 12 controls before dietary randomization was similar, and
      increased in both groups consuming a LGI versus HGI diet (PH-CHD, 0.31 (0.26 to
      0.37) v 0.14 (0.10 to 0.24) mmol/L/min, P < .01; controls, 0.31 (0.1 to 0.53) v
      0.15 (0.06 to 0.23) mmol/L/min, P < .05). Adipocyte IS was greater in PH-CHD
      women on a LGI versus HGI diet (subcutaneous, 50% (20% to 98%) v 13% (1% to 29%);
      omental, 97% (47% to 184%) v 29% (4% to 84%), P < .05). Adipocyte TNF-alpha
      production was higher in women with versus without PH-CHD (subcutaneous, 0.3
      (0.18 to 0.42) v 0.93 (0.39 to 1.30) ng/mL/min; visceral, 0.22 (0.15 to 1.30) v
      0.64 (0.24 to 1.1) ng/mL/min, P < .04, respectively), but was uninfluenced by the
      dietary glycemic index. We conclude that in vitro adipocyte IS is reduced and
      adipocyte TNF-alpha production is increased in premenopausal women with PH-CHD. A
      LGI diet improves both adipocyte IS in women with PH-CHD and in vivo IS in women
      with and without PH-CHD.

PMID- 9781630
TI  - Recurrent hypoglycemia does not impair the cortisol response to
      adrenocorticotropin infusion in healthy humans.
AB  - Previous studies have shown that hypoglycemia may reduce counterregulatory
      responses to subsequent hypoglycemia in healthy subjects and in patients with
      diabetes. The effect of hypoglycemia on the hormonal response to a
      nonhypoglycemic stimulus is uncertain. To test the hypothesis that the cortisol
      response to corticotropin (ACTH) infusion is independent of antecedent
      hypoglycemia, 10 healthy subjects received a standard ACTH infusion (0.25 mg
      Cosyntropin [Organon, West Orange, NJ] intravenously over 240 minutes) at 8:00 AM
      on day 1 and day 3 and a hypoglycemic insulin clamp study (1 mU/kg/min) at 8:00
      AM on day 2. During the hypoglycemic clamp, plasma glucose decreased from 5.0
      mmol/L to 2.8 mmol/L for two periods of 120 minutes (mean glucose, 2.9 +/- 0.03
      and 2.8 +/- 0.02 mmol/L, respectively) separated by a 60-minute interval of
      euglycemia (mean glucose, 4.7 +/- 0.01 mmol/L). Seven subjects also had paired
      control studies in random order during which a 330-minute euglycemic clamp (mean
      glucose, 5.0 +/- 0.11 mmol/L) instead of a hypoglycemic clamp was performed on
      day 2. Basal ACTH (4.6 +/- 0.7 v 2.6 +/- 0.4 pmol/L, P < .02) and basal cortisol
      (435 +/- 46 v 317 +/- 40 nmol/L, P < .02) both decreased from day 1 to day 3
      following intervening hypoglycemia. In contrast, with intervening euglycemia,
      neither basal ACTH (5.9 +/- 1.5 v 4.5 +/- 1.0 pmol/L) nor basal cortisol (340 +/-
      38 v 318 +/- 60 nmol/L) were reduced significantly on day 3 compared with day 1.
      Following interval hypoglycemia, the area under the curve (AUC) for the cortisol
      response to successive ACTH infusions was increased (4,734 +/- 428 nmol/L over
      240 minutes [day 3] v 3,526 +/- 434 nmol/L over 240 minutes [day 1], P < .01).
      The maximum incremental cortisol response was also significantly increased (805
      +/- 63 nmol/L (day 3) v 583 +/- 58 nmol/L (day 1), P < .05). In contrast, the AUC
      for the cortisol response to successive ACTH infusions with interval euglycemia
      (3,402 +/- 345 nmol/L over 240 minutes [day 3] v 3,709 +/- 391 nmol/L over 240
      minutes [day 1] and the incremental cortisol response (702 +/- 62 nmol/L [day 3]
      v 592 +/- 85 nmol/L [day 1] were unchanged. Following exposure to intermittent
      hypoglycemia in healthy humans, fasting morning ACTH and cortisol levels are
      reduced and the incremental cortisol response to an infusion of ACTH is enhanced.
      The enhanced cortisol response to exogenous ACTH infusion after intervening
      hypoglycemia (but not intervening euglycemia) may reflect priming of the adrenal
      gland by endogenous ACTH produced during the hypoglycemia. These data suggest
      that adrenal function testing by exogenous ACTH administration is not impaired by
      prior exposure to hypoglycemia. Moreover, the reduced cortisol response to
      recurrent hypoglycemia in patients with well-controlled diabetes is not likely
      the result of impaired adrenal responsiveness.

PMID- 9781631
TI  - Angiotensin-converting enzyme gene polymorphism is associated with coronary heart
      disease in non-insulin-dependent diabetic patients evaluated for 9 years.
AB  - The insertion/deletion (I/D) polymorphism of the human angiotensin-converting
      enzyme (ACE) gene is a major determinant of circulating ACE levels. Recent
      studies have found the ACE D allele to be associated with an increased risk for
      coronary heart disease (CHD) in diabetic and nondiabetic subjects. This
      association has not been evaluated in prospective studies. We therefore studied
      the relationship between ACE gene I/D polymorphism and CHD in patients with non
      insulin-dependent diabetes mellitus (NIDDM) evaluated for 9 years. The I/D
      polymorphism was determined by polymerase chain reaction (PCR). Overestimation of
      the frequency of the DD genotype was eliminated by insertion-specific primers and
      inclusion of 5% dimethylsulfoxide (DMSO). Eighty-three patients were evaluated
      for a mean period of 9.1 years (range, 7.4 to 10.5). Among them, 64 patients
      showed no CHD at entry. During the follow-up period, 21 patients (37.5%)
      developed CHD. The systolic blood pressure (P = .046), fasting blood glucose (P <
      .01), and prevalence of hypertension (P < .001) increased, while high-density
      lipoprotein (HDL) cholesterol (P < .001) decreased. Patients who developed CHD
      were older than those who did not; the mean age was 59.3 and 53.2 years,
      respectively (P = .003). The prevalence of albuminuria at follow-up examination
      was higher in CHD subjects versus non-CHD subjects (61.9% v 20.9%, P = .012). The
      D allele of the ACE gene was significantly more frequent in subjects with CHD
      versus those without CHD in both follow-up (P = .028, chi2 test) and cross
      sectional (P = .033, chi2 test) settings. No difference could be detected between
      the three genotypes in age, body mass index (BMI), blood pressure, or plasma
      lipid levels. In our logistic regression analysis, the best model selected the DD
      genotype (P = .0105) and age (P = .0407) as significant risk factors for CHD.
      This model classified 89% of the subjects correctly. In conclusion, this 9-year
      prospective study supports the hypothesis that the ACE I/D polymorphism is an
      important and independent risk factor for CHD in patients with NIDDM.

PMID- 9781632
TI  - Simulated postaggression metabolism in healthy subjects: metabolic changes and
      insulin resistance.
AB  - Postaggression metabolism (PAM) is difficult to study in critically ill patients.
      The objective of this study was to simulate PAM in healthy subjects to quantify
      insulin sensitivity under these conditions. Six healthy men (age, 24 +/- 1 years;
      body mass index, 22.0 +/- 0.7 kg/m2 [mean +/- SE]) received an intravenous (i.v.)
      infusion of insulin-counteracting hormones (epinephrine 100 ng/kg/min, glucagon
      16 ng/kg/min, hydrocortisone 5 microg/kg/min, and growth hormone [GH]-releasing
      hormone 50 microg/h) for 4 hours in addition to glucose (270 mg/kg/h). Control
      experiments used glucose only. In additional experiments, insulin sensitivity was
      measured by a two-step hyperinsulinemic glucose clamp with and without
      concomitant hormone infusion (insulin infusion rate, 2.5 and 5.0 mU/kg/min for
      hormone infusion or 1.0 and 2.5 mU/kg/min for control experiments). Plasma stress
      hormones reached levels comparable to severe PAM (epinephrine, 1,085 +/- 89
      pg/mL; glucagon, 1,100 +/- 114 pg/mL; cortisone, 1,004 +/- 32 ng/mL; and GH, 20.6
      +/- 6.1 pg/mL) in the hormone infusion experiment. This resulted in hyperglycemia
      and hyperinsulinemia (steady-state blood glucose, 19.7 +/- 0.4 mmol/L; serum
      insulin, 352 +/-8 pmol/L) in comparison to the control experiments with glucose
      infusion only (maximal blood glucose 7.2 +/- 0.8 mmol/L; serum insulin, 110 +/-
      16 pmol/L). The insulin sensitivity index (S(I)) was 88% +/- 6% lower during
      hormone infusion (0.6 +/- 0.4 mL/min/m2/microU/min) compared with the control
      experiments (4.5 +/- 1.3 mL/min/m2/microU/min). Infusion of insulin-counteracting
      hormones at high doses allows simulation of the changes in carbohydrate
      metabolism observed in PAM in healthy subjects. The observed profound decrease in
      insulin sensitivity explains the hyperglycemia observed in nondiabetic critically
      ill patients. With this experimental setup, standardized investigations of
      therapeutic interventions in PAM should be possible.

PMID- 9781633
TI  - Four-week ethanol intake decreases food intake and body weight but does not
      affect plasma leptin, corticosterone, and insulin levels in pubertal rats.
AB  - Long-term intake of ethanol decreases food intake and inhibits growth in
      experimental rats. The aim of this study was to determine the effect of 4-week
      oral ethanol ingestion on plasma leptin and adrenal function. Male 45-day-old
      Wistar rats were divided into three groups: absolute control (AC), ethanol (E)
      administered 10% (wt/vol) ethanol instead of tap water, and pair-fed (PF) given
      an amount of food corresponding to the food intake of E animals. E rats consumed
      less pelleted diet (74% cumulative total intake); however, this caloric deficit
      was compensated by ethanol ingestion. Net water intake in E animals was 76% of
      that in the control groups. The body growth of both E and PF rats was stunted
      compared with AC animals, but E rats were heavier than PF rats. The plasma leptin
      level was similar in E and AC and decreased in PF animals. There were no
      differences in plasma osmolality or glycemia among the three groups. Plasma
      insulin was decreased in PF compared with both AC and E rats. Plasma
      corticosterone was not affected by ethanol, but was increased in the food
      restricted (PF) group. Although there were no differences in basal adrenal
      corticosterone production in vitro, there was a slightly higher response to
      corticotropin (ACTH) in E rats. We conclude that drinking 10% ethanol decreased
      the dietary intake and body growth. These changes were not mediated by plasma
      leptin changes. Although alcohol ingestion and its energy content theoretically
      normalized the total energy intake and prevented the decrease of plasma leptin,
      the growth of young rats was inhibited. Drinking 10% ethanol instead of tap water
      for 4 weeks did not stimulate basal adrenal activity.

PMID- 9781634
TI  - Intracerebroventricular administration of leptin markedly enhances insulin
      sensitivity and systemic glucose utilization in conscious rats.
AB  - This study examines the acute, subacute (overnight), and chronic (7-day) effects
      of intracerebroventricular (i.c.v.) administration of r-metMuLeptin on insulin
      sensitivity and systemic glucose turnover in conscious unrestrained rats (body
      weight, 250 to 300 g). Under postabsorptive conditions, acute i.c.v. leptin ([AL]
      10 microg bolus) did not affect tracer (3-(3)H-glucose)-determined glucose
      production (GP) and utilization (GU) rates during the 2-hour hyperinsulinemic (2
      mU x kg(-1) x min(-1)) euglycemic clamp. Chronic i.c.v. leptin ([CL] 10 microg/d
      for 7 days) administered by osmotic pumps markedly reduced the daily food
      consumption (P < .05), body weight (P < .05), and postabsorptive basal plasma
      glucose level (P < .01). During the glucose clamp, GP was markedly suppressed
      (55%) with CL (P < .001 v vehicle and pair-fed control groups). The insulin
      induced increment in GU was significantly greater with CL (23.3 +/- 1.8 mg(-1) x
      kg(-1) x min(-1)) than with vehicle (16.9 +/- 0.2) and pair-feeding (17.1 +/-
      0.6, both P < .001). Subacute i.c.v. leptin ([SL] 10 microg bolus) moderately but
      insignificantly decreased overnight food consumption (-18%) and body weight (-2.5
      +/- 1.5 g). The glucose infusion rate during the final 60 minutes of the glucose
      clamp was 43% greater than for the vehicle group (P < .0001). SL also
      significantly increased GU (P < .005) and suppressed GP (P < .05) during the
      glucose clamp. Thus, we conclude that i.c.v. administered leptin has strong
      actions on the central nervous system that result in significant increases in
      insulin sensitivity and systemic GU, and these effects are achieved as early as
      overnight after leptin administration.

PMID- 9781635
TI  - Small low-density lipoproteins and vascular cell adhesion molecule-1 are
      increased in association with hyperlipidemia in preeclampsia.
AB  - The pregnancy disorder preeclampsia is characterized by endothelial cell
      dysfunction that may be promoted by abnormal increases in circulating lipids,
      particularly triglycerides and free fatty acids. Serum triglyceride concentration
      is a major regulatory determinant of low-density lipoprotein (LDL) size and
      density distribution. Smaller, denser LDL particles have several intrinsic
      properties capable of inducing endothelial dysfunction. The present nested, case
      control study of gestationally matched preeclamptic and normal pregnant women
      tested the hypothesis that hypertriglyceridemia in preeclampsia is accompanied by
      decreases in LDL peak particle diameter (predominant LDL size). Plasma LDL peak
      particle diameter was determined by nondenaturing 2% to 16% polyacrylamide gel
      electrophoresis. Correlations of LDL diameter with the concentration of serum
      triglycerides, free fatty acids, total cholesterol, LDL-cholesterol, and
      apolipoprotein B (apo B) were determined. In the same individuals, we measured
      serum concentrations of a marker of vascular dysfunction previously reported to
      be increased in preeclampsia, soluble vascular cell adhesion molecule-1 (VCAM-1),
      and examined the association of VCAM-1 with LDL diameter and serum lipids. LDL
      peak particle diameter was decreased in preeclampsia relative to normal pregnancy
      (P < .01). The LDL-cholesterol:apo B ratio, which frequently decreases with
      decreasing LDL diameter, was also decreased (P < .04). Triglyceride
      concentrations were increased in preeclampsia (P < .0002), and there was a
      significant inverse relationship between LDL peak particle diameter and
      triglycerides (r = -.55, P < .02). Serum soluble VCAM-1 concentrations were
      markedly increased in preeclampsia (P < .0003). Apo B (P < .004), free fatty
      acids (P < .01), total cholesterol (P < .01), and LDL-cholesterol (P < .02) were
      also increased. VCAM-1 correlated with apo B (r = .50, P < .03) and LDL
      cholesterol (r = .50, P < .03), but showed no relationship with the LDL diameter,
      LDL-cholesterol:apo B ratio, or other lipids. We conclude that the predominance
      of smaller, denser LDL, a potential contributor to endothelial cell dysfunction,
      is a feature of preeclampsia. However, the serum VCAM-1 level, one indicator of
      endothelial involvement, may be influenced more by quantitative lipoprotein
      changes (serum apo B or LDL-cholesterol) than by LDL particle size.

PMID- 9781636
TI  - Acute and delayed effects of a single-dose injection of interleukin-6 on thyroid
      function in healthy humans.
AB  - Interleukin-6 (IL-6) is produced in response to inflammatory and noninflammatory
      stress and acts as the principal regulator of the acute-phase protein response.
      IL-6 stimulates the hypothalamic-pituitary-adrenal axis and may be involved in
      the thyroid function abnormalities observed in nonthyroidal illness (NTI). This
      study examined the effects of single-dose IL-6 (3 microg/kg subcutaneously
      [s.c.]) in healthy human subjects: 19 received IL-6 and 13 received control
      saline injection. The dose of IL-6 was chosen on the basis of previous studies
      indicating that the peak IL-6 level after injection reaches concentrations
      observed with major stress such as abdominal surgery. Plasma levels of
      thyrotropin (TSH), free thyroxine (FT4), total T4, 3,5-3'-L-triiodothyronine
      (T3), 3,3'-5'-L-triiodothyronine or reverse T3 (rT3), and thyroxine-binding
      globulin (TBG) were measured over a 4-hour period and 24 hours after IL-6
      injection. Plasma TSH levels were 27% lower 240 minutes after IL-6 relative to
      control levels (0.93 +/- 0.10 v 1.28 +/- 0.18 mIU/mL, P = .001), but recovered by
      24 hours. Plasma FT4 was elevated at 240 minutes compared with the controls (1.16
      +/- 0.04 v 1.03 +/- 0.03 ng/dL, P = .0002). T4 levels were also elevated at 240
      minutes (7.8 +/- 0.36 v 7.05 +/- 0.37 microg/dL, P = .0003). TBG levels were not
      significantly changed at this time point. At 24 hours, T3 levels were 19% lower
      than the control values (87.6 +/- 5.1 v 108.5 +/- 5.4 ng/dL, P = .0002); plasma
      rT3 levels were elevated by 21% compared with control levels (30.6 +/- 1.7 v 24.3
      +/- 1.3 ng/dL, P = .002), while FT4 levels returned to normal. The changes in
      T3/rT3 levels were reminiscent of the pattern observed in NTI that may be due to
      inhibition of type-1 5'-deiodinase. Cortisol levels were greatly elevated after
      IL-6 compared with control values; peak levels were observed 120 minutes after IL
      6 injection (28.7 +/- 1.6 v 9.5 +/- 1.0 ng/dL, P < .0001). This elevation in
      cortisol may have contributed to the suppression of TSH levels and inhibition of
      type-1 5'-deiodinase activity. Alternatively, IL-6 may have suppressed TSH
      secretion via a direct suprapituitary action. The elevation of T4 and FT4 levels
      may have been due to inhibition of T4 degradation at the liver and/or by direct
      action of IL-6 on the thyroid gland. These findings demonstrate the potent
      effects of IL-6 on thyroid hormone metabolism in healthy individuals, and suggest
      that IL-6 may act directly or indirectly at two or more sites on thyroid hormone
      secretion and metabolism.

PMID- 9781637
TI  - Evolving concepts in endometrial carcinogenesis: importance of DNA repair and
      deregulated growth.

PMID- 9781638
TI  - Rapid growth of cutaneous metastases after surgical resection of thrombospondin
      secreting small blue round cell tumor of childhood.
AB  - In animal models, the importance of tumor-derived antiangiogenic factors in
      controlling metastases has been demonstrated by the growth acceleration of
      distant metastases after surgical excision of a primary tumor mass. We report the
      case of an infant who developed rapidly growing cutaneous metastases after
      surgical resection of a neoplasm of an upper extremity. The tumor was
      undifferentiated, with some morphological features of primitive neuroectodermal
      tumor. To test the possibility that the primary tumor was secreting an angiogenic
      inhibitor, cells from the primary tumor were grown in culture, and the culture
      medium was tested with an in vitro endothelial cell migration assay and Western
      blot. The cultured cells secreted sufficiently high levels of an angiogenic
      inhibitor to overcome the inducing ability of vascular endothelial growth factor
      and basic fibroblast growth factor. One of the secreted proteins was
      thrombospondin-1, a potent antiangiogenic glycoprotein. The rapid dissemination
      of distant metastases after resection of the primary tumor in this case suggests
      that tumor-derived angiogenic inhibitors are important in maintaining the local
      net balance of angiogenic mediators controlling the growth of micrometastasis.

PMID- 9781639
TI  - Paragangliomas of the head and neck region show complete loss of heterozygosity
      at 11q22-q23 in chief cells and the flow-sorted DNA aneuploid fraction.
AB  - Nonchromaffin paragangliomas of the head and neck region, also known as glomus
      tumors, are usually benign neoplasms consisting of clusters of chief cells
      surrounded by sustentacular cells arranged in so-called 'Zellballen.' Most of the
      patients have a familial background. In a previous study, examining all
      chromosome arms, we found loss of heterozygosity (LOH) predominantly at the
      chromosome 11q22-q23 region, where the disease causing gene PGL1 has been located
      by linkage analysis. However, all tumors showed only partial loss of allele
      signal intensities, and it was not clear whether this represented allelic
      imbalance or cellular heterogeneity. In the current study, we have performed LOH
      analysis for the 11q22-q23 region on DNA-aneuploid tumor cells, enriched by flow
      sorting, and on purified chief cell fractions obtained by single-cell
      microdissection. Complete LOH was found for two markers (D11S560 and CD3D) in the
      flow-sorted aneuploid fractions, whereas no LOH was found in the diploid
      fractions of three tumors. The microdissected chief cells from two of these
      tumors also showed complete LOH for both markers, indicating that the chief cells
      are clonal proliferated tumor cells. These results indicate that the PGL1 gene is
      likely to be a tumor suppressor gene, which is inactivated according to the two
      hit model of Knudson. Furthermore, it shows that chief cells are a major if not
      the sole neoplastic component of paragangliomas.

PMID- 9781640
TI  - Heat shock protein 72 expression in osteosarcomas correlates with good response
      to neoadjuvant chemotherapy.
AB  - Although the therapeutic outcome of osteosarcoma patients has improved
      dramatically within the last 20 years because of combined neoadjuvant
      chemotherapy and surgery, the problem of drug resistance remains. Thus far,
      markers that can predict the response to chemotherapy at the time of biopsy are
      not available. Heat shock proteins (hsp) 60, 72, and 73 have been shown to play a
      role in tumor immunity, and our study investigated their expression in human
      osteosarcomas and nonmalignant bone tumors before neoadjuvant chemotherapy.
      Immunohistochemical evaluations of hsp expression was performed on paraffin
      embedded sections of 45 patients (17 female, 28 male, aged 6.5 to 62 years; mean,
      19.4 years) with high-grade osteosarcoma at the time of biopsy, before
      preoperative chemotherapy. These results were correlated to histological response
      to chemotherapy, tumor size, age, alkaline phosphatase serum levels, and duration
      of symptoms. Thirty-four patients (15 male, 19 female, mean age 27 years) with
      osteoblastoma, osteoid-osteoma, or fibrous dysplasia served as nonmalignant
      controls. Hsp60 was uniformly found in the cytoplasm of both benign and malignant
      bone tumors. Nuclear hsp73 expression quantitatively increased in osteosarcoma
      cells. Hsp72 was significantly overexpressed in osteosarcomas (17 of 45, 38%)
      compared with nonmalignant bone tumors (1 of 34, 2.9%; P < .001). Hsp72-positive
      osteosarcomas responded better to neoadjuvant chemotherapy than hsp72-negative
      cases (P < .001), co-express hsp60, and correlate with higher tumor size (P <
      .005) and location in the distal femur. No differences were observed relative to
      age, gender, duration of symptoms, alkaline phosphatase levels, or hsp73
      expression between hsp72-positive and hsp72-negative tumors. Hsp72 expression
      seemed to be a predictive immunohistochemical marker for osteosarcoma, because it
      is the first marker to prospectively correlate to response to neoadjuvant
      chemotherapy. It therefore, may be of importance in preoperative therapy regimens
      for nonresponding high-risk patients.

PMID- 9781641
TI  - Consistency achieved by 23 European pathologists in categorizing ductal carcinoma
      in situ of the breast using five classifications. European Commission Working
      Group on Breast Screening Pathology.
AB  - The increased detection of ductal carcinoma in situ (DCIS) by mammographic
      screening, the greater use of breast-conserving surgery, and the recognition that
      certain histological subtypes are associated with a greater risk of local
      recurrence has led to the formulation of several new classifications of DCIS in
      recent years. There are, however, no data concerning the degree of consistency
      with which these schemes can be applied by reasonable numbers of pathologists.
      Thirty-three cases of DCIS were thus examined by a working group of 23 European
      pathologists who categorized them using five recently published classifications:
      (1) that of the European Pathologists' Working Group based on differentiation (a
      combination of nuclear grade and cell polarization) with categories of poorly,
      intermediately, and well differentiated; (2) one based entirely on nuclear grade
      with categories of high, intermediate, and low, currently in use in the UK
      national and EC-funded breast screening programs; (3) the same classification in
      which only two categories, high nuclear grade and other, were used; (4) the Van
      Nuys system in which lesions are divided into high grade, non-high grade with
      necrosis and non-high grade without necrosis; and (5) a two-category
      classification based entirely on the presence or absence of comedo necrosis. Of
      the three systems with three categories, Van Nuys gave the highest overall kappa
      statistic of 0.42. Others gave similar values of 0.37 and 0.35 showing that
      assessing cell polarization in addition to nuclear grade neither improves nor
      worsens consistency. In all three systems, the middle category was associated
      with the lowest value for kappa. Of the two systems with two categories, that
      based on nuclear grade gave the highest overall kappa of 0.46 and that based on
      comedo necrosis the lowest of 0.34. The most robust histological features were
      thus high- and low-grade nuclei and necrosis as long as the latter did not
      involve the recognition of a comedo growth pattern. These values probably
      represent the maximum achievable, at least by reasonable numbers of pathologists
      in everyday practice. They are better than those previously reported for
      classification based entirely on architecture, but further improvement is needed.

PMID- 9781642
TI  - Clonal analysis of renal sporadic angiomyolipomas.
AB  - Renal angiomyolipomas are benign tumors composed of variable amounts of mature
      fat, smooth muscle, and thick-walled blood vessels. They occur either
      sporadically or in association with tuberous sclerosis. Such tumors are
      considered as hamartomas, but few data are available concerning their
      pathogenesis. Indeed, it is not known whether angiomyolipoma is a congenital
      malformation or a neoplastic process. To answer this question, we assessed the
      clonality of sporadic angiomyolipomas using molecular analysis. Seven women (mean
      age, 59 years) with renal angiomyolipomas were included. DNA of the tumor and the
      normal adjacent kidney was extracted from archival paraffin-embedded tissue. DNA
      methylation pattern at a polymorphic site on the HUMARA gene was studied by
      polymerase chain reaction (PCR) amplification after methylation-sensitive enzyme
      digestion. This procedure enables the differentiation between polyclonal and
      monoclonal lesions according to their X-chromosome inactivation pattern. Five of
      the seven women included were informative for the HUMARA gene. The mean size of
      the angiomyolipomas was 53 mm (range, 18 to 110). In one case, a tumor thrombus
      was observed in the inferior vena cava. Clonal analysis showed that all of the
      angiomyolipomas and the tumor thrombus studied were monoclonal. This study shows
      that sporadic angiomyolipomas are monoclonal lesions consistent with neoplastic
      disorders. This result strongly supports the hypothesis that angiomyolipomas
      arise from the clonal proliferation of an uncommited cell, which will further
      evolve toward different cell types.

PMID- 9781643
TI  - Virological and biological characteristics of cervical intraepithelial neoplasia
      grade I with marked koilocytotic atypia.
AB  - The aim of this study was to evaluate virologic and biological significance of
      marked koilocytotic atypia observed in some cases of grade I cervical
      intraepithelial neoplasia (CIN I). Thirty-one CIN I cervical biopsy specimens
      with marked koilocytotic atypia, defined by the presence of meganuclei in the
      superficial epithelial layers, were compared to 37 CIN I biopsy specimens with
      usual koilocytes for (1) the human papillomavirus (HPV) type and signal pattern
      as detected by nonisotopic in situ hybridization (ISH); (2) the proliferation
      index assessed by Ki 67 immunostaining and (3) the p53 labeling pattern.
      Interobserver agreement for meganuclei was excellent (k = 0.9). Twenty-five out
      of 68 biopsies (37%) were positive by ISH for the 6 of 11 HPV probe, 30 (44%) for
      the 16-18 probe, and 7 (10%) for the 31/33 HPV probe, 6 (9%) were negative for
      ISH. The presence of meganuclei was strongly related to high and intermediate
      risk HPV type (P = 0.0001). The sensitivity and specificity of meganuclei for the
      detection of high or intermediate risk HPV in CINI were 73 and 87%, respectively.
      Loss of p53 immunostaining in the lower third of the epithelium was also related
      to the presence of meganuclei (P < .05), but the MIB-1 index and ISH labeling
      pattern were not. In conclusion, marked koilocytotic atypia in CIN I is a
      reliable and sensitive marker for infection by high or intermediate-risk HPV, and
      might be a guide to therapy.

PMID- 9781644
TI  - Polymerase chain reaction amplification of archival material for Epstein-Barr
      virus, cytomegalovirus, human herpesvirus 6, and parvovirus B19 in children with
      bone marrow hemophagocytosis.
AB  - Bone marrow hemophagocytosis may occur as an incidental finding, or it may be a
      manifestation of a systemic and potentially lethal disorder. When systemic, the
      proliferation is termed hemophagocytic lymphohistiocytosis (HLH), a
      clinicopathologic entity characterized by a widespread proliferation of benign
      hemophagocytic histiocytes, fever, pancytopenia, deranged liver function, and
      frequently coagulopathy and hepatosplenomegaly. A variety of infectious agents,
      including Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6
      (HHV6), and parvovirus B19 (PVB19), have been associated with HLH, but the
      relative frequency of each using one technique has not been evaluated. In
      addition, infectious causes of incidental bone marrow hemophagocytosis, not
      occurring in the setting of HLH, have not been evaluated. Review of bone marrow
      reports from bone marrow examinations done between December 1986 and June 1997
      showed that 20 children aged 2 months to 15 years had bone marrow examinations
      that indicated hemophagocytosis. Archival materials from 19 patients were
      successfully retrieved, and DNA was extracted from archived unstained coverslips
      with subsequent polymerase chain reaction for EBV, CMV, HHV6, and PVB19 genomic
      DNA. DNA extracted from 16 bone marrow specimens of age-matched children was used
      as negative controls. Eleven of the 19 patients fulfilled the clinical and
      pathological criteria for HLH; the remaining eight patients had isolated
      hemophagocytosis without a systemic presentation. Viral DNA was detected in 8 of
      11 patients with HLH but in none of eight patients with isolated
      hemophagocytosis. EBV was present in five of the bone marrows, followed in
      frequency by HHV6, CMV, and PVB19. Infection with more than one agent was present
      in three patients. Only one control patient was positive for HHV6 DNA; the
      remaining control patients were negative for all viruses. Viral infection,
      detected by PCR analysis of bone marrow, is a common finding in patients with HLH
      but not in patients with isolated bone marrow hemophagocytosis. This technique
      may provide another marker to aid in the diagnosis of HLH and suggests a
      different cause of hemophagocytosis occurring in patients with and without HLH.

PMID- 9781646
TI  - Mitotic cyclins and cyclin-dependent kinases in melanocytic lesions.
AB  - Recent evidence has implicated cyclins and cyclin-dependent kinases in the
      evolution and progression of various malignancies. We studied the
      immunohistochemical expression of cyclin A, cyclin B, and cyclin-dependent kinase
      p34cdc2 in a broad spectrum of benign and malignant melanocytic lesions. Formalin
      embedded, parrafin-fixed tissue sections from 66 malignant melanomas (MM) and 60
      benign nevi were examined for the expression of these cell-cycle proteins. The
      results were compared with the standard proliferative marker Ki-67 and mitotic
      index. MM showed significantly higher immunoreactivity for cyclin A, cyclin B,
      p34cdc2, and Ki-67 compared with benign nevi. Cyclin A, p34cdc2, and Ki-67
      displayed strong co-expression in MM. Overexpression of cyclin A and p34cdc2
      correlated with histological type, mitotic activity, Ki-67 index, tumor
      thickness, Clark's level, and clinical outcome in MM. In invasive MM, increased
      immunostaining of cyclin A and Ki-67 were associated with decreased patient
      survival. These findings indicate potential roles of mitotic cyclins and cyclin
      dependent kinases in the pathogenesis and progression of malignant melanoma.

PMID- 9781647
TI  - Kaposi's sarcoma-associated herpesvirus in Kikuchi's disease.
AB  - Kikuchi's disease is a fairly common self-limited disorder among Orientals that
      usually involves the cervical lymph nodes of young individuals and occurs
      predominantly in females. Frequently, the disease is associated with fever or flu
      like symptoms, an elevated erythrocyte sedimentation rate (ESR), neutropenia, and
      lymphocytosis with atypical lymphocytes in the peripheral blood, suggesting a
      viral origin. However, no infectious agent has been identified. The presence of
      Kaposi sarcoma-associated herpesvirus, known as human herpesvirus 8 (KSHV/HHV 8),
      was investigated by polymerase chain reaction (PCR) in archival tissue from 26
      cases of Kikuchi's disease using published sequences of KSHV/HHV 8 as primers.
      PCR products were further characterized by Southern blot analysis. Forty reactive
      lymph nodes and a case of Kaposi sarcoma (KS) were included as negative and
      positive controls, respectively. Patients consisted of 10 men and 16 women with a
      mean age of 27 years. All patients were previously healthy and presented with
      cervical or axillary lymphadenopathy. None were positive for human
      immunodeficiency virus (HIV) or otherwise immunocompromised. Viral DNA was
      amplified by PCR in six cases of Kikuchi's disease (23%) and the control KS
      tissue. Southern blot analysis confirmed that the amplified products were
      KSHV/HHV 8. In the reactive lymph nodes, no viral genome was amplified by PCR.
      The presence of DNA sequences of KSHV/HHV 8 in a substantial portion of Kikuchi's
      disease suggests that KSHV/HHV 8 might play an important role in the pathogenesis
      of a subset of Kikuchi's disease.

PMID- 9781645
TI  - Medullary thyroid carcinoma: search for histological predictors of survival (109
      proband cases analysis).
AB  - A group of 13 pathologists belonging to the French Calcitonin Tumor Study Group
      (GETC: Groupe d'Etude des Tumeurs a Calcitonine) examined the histological slides
      and medical records of 109 proband cases of medullary thyroid carcinoma (MTC)
      diagnosed on clinical features. The cases belonged to the various forms of the
      disease (80 sporadic and 29 familial MTC). The aim of the study was to detect
      histological predictors for survival by comparing morphological data from
      patients killed by the disease versus the others. Twenty-seven histological
      parameters were considered, including cellular heterogeneity, shape of the cells,
      and cytoplasmic characteristics. Other parameters such as sex, age, and phenotype
      of the disease were also studied. First, predictive parameters of interest on
      survival function were selected by univariate analysis (Mantel-Cox test). Then,
      the extracted parameters were tested in a multifactorial analysis using the Cox's
      forward stepping proportional hazard model. Five parameters were significantly
      associated with a lower survival function: presence of necrosis in the tumor (P =
      .001), squamous pattern (P = .002), age over 45 years (P = .004), presence of
      oxyphil cells in the tumor and absence of cells with intermediate cytoplasm (P =
      .025), less than 50% of calcitonin immunoreactive cells in the tumor (P = .04).

PMID- 9781649
TI  - Spitz nevus versus spitzoid malignant melanoma: an evaluation of the current
      distinguishing histopathologic criteria.
AB  - Because of the well-known difficulty in distinguishing between Spitz nevi and
      spitzoid malignant melanomas at the microscopic level, the critical importance of
      this task notwithstanding, expert dermatopathologists across the world have
      strenuously endeavored to identify histopathologic criteria that would assist
      microscopists in this effort. Many reports itemizing such criteria are extant.
      The objective of the current study was to determine which of these criteria serve
      as the most consistent discriminators. Using a population of 11 spitzoid
      melanomas and 12 Spitz nevi, we evaluated six sets of criteria purported to be
      helpful in differentiating between these entities. Overall, we found that six
      features had significant distinguishing capacity, namely, (1) Kamino bodies, (2)
      a brisk mitotic rate, (3) mitoses close to the base of the lesion, (4) abnormal
      mitoses, (5) symmetry, and (6) uniformity of nests from side to side. It is
      noteworthy that the first three of these rank among the six criteria itemized
      repeatedly in 50% or more of the sets of criteria evaluated.

PMID- 9781648
TI  - Intracystic (encysted) papillary carcinoma of the breast: a clinical,
      pathological, and immunohistochemical study.
AB  - Intracystic papillary carcinoma (IPC) of the breast is a rare tumor with
      predilection for elderly women and distinctive pathological features that must be
      distinguished from ductal carcinoma in situ (DCIS) of papillary type and from
      invasive papillary carcinoma. The clinical, radiological, and pathological
      features of 29 cases of IPC are reported. The cases were divided into three
      groups (IPC alone, associated with DCIS, or associated with invasive carcinoma)
      and studied in terms of their size, predominant architectural pattern, nuclear
      grade, and presence of necrosis. Immunohistochemical studies were performed to
      evaluate the c-erbB2 oncoprotein, estrogen receptors, and ki-67 antigen
      expression. The median age of the patients was 75 years. Microscopically, nine
      tumors (31.0%) were IPC alone, nine (31.0%) had IPC associated with DCIS, and 11
      (38.0%) were IPC associated with invasive carcinoma. Most of the IPC cases had
      low or intermediate nuclear grade, no necrosis, strongly expressed estrogen
      receptor, and was negative for c-erbB-2. Nuclear grade 3 and necrosis were found
      only in cases of IPC associated with invasive carcinoma. The median Ki-67 antigen
      expression was 10.6%. One patient with IPC alone had a recurrence 5 years later.
      Lymph node metastases were found in one patient who had the tumor with the
      biggest invasive area. IPC is a low-grade carcinoma with overall good prognosis.
      However, there is a high frequency of DCIS or invasive carcinoma associated with
      it, and the prognosis of these cases is related to the type, grade, and size of
      the associated lesions.

PMID- 9781650
TI  - LOH at 16p13 is a novel chromosomal alteration detected in benign and malignant
      microdissected papillary neoplasms of the breast.
AB  - Papillary carcinoma of the breast is a variant of predominantly intraductal
      carcinoma characterized by a papillary growth pattern with fibrovascular support.
      Loss of heterozygosity (LOH) was evaluated at multiple chromosomal loci
      (including loci reported to show frequent genetic alterations in breast cancer)
      to determine the frequency of genetic mutations in these tumors and their
      precursors. Thirty-three papillary lesions of the breast (6 papillary carcinomas,
      12 carcinomas arising in a papilloma, and 15 intraductal papillomas with florid
      epithelial hyperplasia) were retrieved from the files of the Armed Forces
      Institute of Pathology (AFIP). Tumor cells and normal tissue were microdissected
      in each case and screened for LOH at INT-2 and p53 as well as several loci on
      chromosome 16p13 in the TSC2/PKD1 gene region (D16S423, D16S663, D16S665). LOH on
      chromosome 16p13 was present in 10 of 16 (63%) informative cases of either
      papillary carcinoma or carcinoma arising in a papilloma as well as in 6 of 10
      (60%) informative cases of intraductal papilloma with florid epithelial
      hyperplasia (IDH). One case showed simultaneous LOH in both the florid IDH and
      carcinoma components of a papilloma. LOH was not observed at either INT-2 or p53
      in any of the papillary carcinomas or papillomas with florid IDH. In conclusion,
      a high frequency of LOH at chromosome 16p13 (the TSC2/PKD1 gene region) is in
      both papillary carcinomas of the breast as well as in papillomas with florid IDH,
      including a case with LOH present simultaneously in both components. These
      findings suggest that chromosome 16p contains a tumor suppressor gene that
      frequently is mutated early in papillary neoplasia.

PMID- 9781651
TI  - Patterns of high-grade prostatic intraepithelial neoplasia associated with
      clinically aggressive prostate cancer.
AB  - High-grade prostatic intraepithelial neoplasia (PIN) is the only widely accepted
      precursor lesion for prostatic adenocarcinoma (PCa). However, the spread of
      established PCa within prostatic ducts may be indistinguishable morphologically
      from high-grade PIN. By convention, all cytologically malignant cellular
      proliferations within prostatic ducts have been lumped into a PIN category,
      although there have been recent attempts by McNeal to develop reproducible
      criteria to separate high-grade PIN from the spread of established PCa within
      prostatic ducts--intraductal carcinoma (IDCa). Using McNeal's criteria for IDCa,
      we studied whole-mount sections from 252 patients with pT3NO PCa for the presence
      of IDCa and correlated the presence or absence of IDCa with Gleason score, total
      tumor volume, surgical margin status, seminal vesicle involvement, and disease
      progression. Patients with IDCa had higher Gleason score and total tumor volume
      and were more likely to show seminal vesicle involvement and disease progression
      than those patients without IDCa. In addition, IDCa was of independent prognostic
      significance. Total tumor volume and surgical margin status had no independent
      prognostic significance in this data set.

PMID- 9781652
TI  - Intramural coronary artery dysplasia of the ventricular septum and sudden death.
AB  - We report four cases of sudden unexpected death in three males and one female
      aged 12 to 31 years. Death occurred during exercise in three of four cases, and
      there was no history of sudden death or previous cardiac history in any patient.
      At autopsy, there was marked intramural coronary artery dysplasia of the
      ventricular septum, accompanied in three of the four cases by myocardial
      fibrosis. The arterial dysplasia was characterized by severe medial thickening
      with smooth muscle cell disorganization and marked luminal narrowing. There was
      no evidence of myofiber disarray or asymmetric septal hypertrophy to suggest
      hypertrophic cardiomyopathy. Other than an ostium secundum type atrial septal
      defect in one case, there were no associated cardiac or extracardiac lesions
      found at complete autopsy of these individuals. We conclude that small vessel
      disease of intramural coronary arteries of the ventricular septum may be an
      isolated finding leading to sudden cardiac death in young adults.

PMID- 9781654
TI  - Expression of CD44 (HCAM) in small lymphocytic and mantle cell lymphoma.
AB  - Small lymphocytic lymphoma (SLL) and mantle cell lymphoma (MCL) are small B-cell
      lymphomas that share many morphological and immunophenotypic features, both
      expressing the T-cell antigen CD5. Because of this, there is speculation that
      these two lymphomas may have a common origin, both arising from the mantle zone
      of the lymph node. CD44 (HCAM), a glycoprotein "homing receptor," has been
      reported as a marker of small B-cell lymphomas for determining behavior as well
      as the nodal cell of origin. Intensity of CD44 expression also has been
      correlated with dissemination of lymphoma. We studied 50 cases with classic
      features of SLL (30 cases) or MCL (20 cases). Immunophenotypic analysis was
      performed on paraffin sections. All cases of MCL and SLL were CD20 positive; CD5
      was expressed in 19 of 25 (76%) SLL and 11 of 15 (73%) MCL. Cyclin D1 was
      expressed in 11 of 17 (76%) MCL and no cases of SLL. CD43 coexpression was seen
      in 27 of 29 (93%) SLL and 17 of 19 (89%) MCL. CD23 was positive in 25 of 28 (89%)
      SLL and 2 of 20 (10%) MCL. Bcl-2 was positive in 18 of 22 (82%) SLL and 15 of 16
      (94%) MCL. CD44 was positive with moderate to strong intensity in 11 of 30 SLL
      and 15 of 20 MCL. Peripheral blood involvement did not correlate with CD44
      immunoreactivity. MCL tended to have intense CD44 immunoreactivity, whereas SLL
      tended to show weaker CD44 intensity. This trend in the intensity of CD44 in MCL
      suggests that CD44 may be helpful in distinguishing SLL from MCL and possibly
      elucidating the origin of these CD5-positive B-cell neoplasms.

PMID- 9781653
TI  - Rimmed vacuoles with beta-amyloid and ubiquitinated filamentous deposits in the
      muscles of patients with long-standing denervation (postpoliomyelitis muscular
      atrophy): similarities with inclusion body myositis.
AB  - In the chronically denervated muscles of patients with prior paralytic
      poliomyelitis, there are secondary myopathic features, including endomysial
      inflammation and rare vacuolated fibers. To assess the frequency and
      characteristics of the vacuoles and their similarities with those seen in
      inclusion body myositis (IBM), we examined 58 muscle biopsy specimens from
      patients with prior paralytic poliomyelitis for (1) the presence of rimmed
      vacuoles; (2) acid-phosphatase reactivity; (3) Congo-red-positive amyloid
      deposits; (4) electron microscopy, searching for tubulofilaments; and (5)
      immunoelectron microscopy, using antibodies against beta-amyloid and ubiquitin.
      We found vacuolated muscle fibers in 18 of 58 (31%) biopsies, with a mean
      frequency of 2.06 +/- 0.42 fibers per specimen. The vacuoles contained acid
      phosphatase-positive material in 6 of the 18 (33.30%) specimens and stained
      positive for Congo red in five (27.80%). By immunoelectron microscopy, the
      vacuoles contained 5.17 +/- 0.13 nm fibrils and 14.9 +/- 0.31 nm filaments that
      immunoreacted with antibodies to beta-amyloid and ubiquitin in a pattern
      identical to the one seen in IBM. We conclude that vacuolated muscle fibers
      containing filamentous inclusions positive for amyloid and ubiquitin are not
      unique to IBM and the other vacuolar myopathies but can also occur in a chronic
      neurogenic condition, such as postpoliomyelitis. The chronicity of the underlying
      disease, rather than the cause, may lead to vacuolar formation, amyloid
      deposition, and accumulation of ubiquitinated filaments.

PMID- 9781655
TI  - Pathobiologic characteristics of hereditary breast cancer.
AB  - Patients with hereditary breast cancer (HBC) present at a young age with breast
      cancers that show adverse pathological characteristics such as high nuclear
      grade, negative hormone receptor status, and high proliferation indices.
      Surprisingly, the clinical course has been reported to be comparable or improved
      compared with patients with nonhereditary breast cancer (non-HBC). To determine
      whether there are any molecular markers that might help explain this paradox
      between pathologically aggressive neoplasms in patients with HBC and the lack of
      extreme clinically aggressive disease, we studied several molecular parameters in
      a group of 34 breast cancer patients with mutations in either the BRCA1 or BRCA2
      tumor suppressor genes and compared them with a group of 20 breast cancer
      patients with non-HBC. In general, patients with HBC had tumors that were of
      higher nuclear grade, contained a higher population of proliferating cells,
      showed increased expression of DNA topoisomerase II-alpha (topo II-alpha), lacked
      hormone receptors, and were more likely to show immunopositivity for the p53
      tumor suppressor gene. Additionally, tumors from patients with HBC showed a
      decreased angiogenesis compared with controls. The decreased angiogenesis and the
      elevated expression of topo II-alpha (an anticancer drug target) may, in part,
      explain the lack of correlation between clinical course and histological
      characteristics in patients with HBC.

PMID- 9781656
TI  - Unbalanced chromosomal aberrations in neuroendocrine lung tumors as detected by
      comparative genomic hybridization.
AB  - Typical and atypical carcinoids (TC, ATC) and small (SCLC) and large cell
      neuroendocrine carcinomas (LCNEC) constitute the spectrum of neuroendocrine lung
      tumors. Chromosomal aberrations have not been studied in LCNEC and only rarely in
      carcinoids. Only SCLCs have been investigated frequently for chromosomal
      aberrations. We compared three typical and four atypical carcinoids, one atypical
      carcinoid/SCLC mixed type, three SCLC, and three LCNEC for chromosomal gains and
      losses using comparative genomic hybridization. Typical carcinoids showed either
      no changes or only few chromosomal gains. Atypical carcinoids appeared
      genetically heterogeneous: One case had no aberrations, and three cases had few
      aberrations; two of them showed a deletion of 11q. SCLC and LCNEC were
      characterized by many gains and losses, especially similar changes of 3p, 5q, 5p,
      and 13q. Although ATC resemble LCNEC morphologically, there were no similarities
      at the genetic level. We have found a reciprocal relationship of prognosis and
      the amount of aberrations. TCs and ATCs with few chromosomal changes have the
      best prognosis, whereas SCLCs and LCNECs were generally characterized by a great
      amount of aberrations and worst prognosis. There was no unbalanced aberration
      common in all types of neuroendocrine tumors of the lung.

PMID- 9781657
TI  - Correlation of proliferation indices, apoptosis, and related oncogene expression
      (bcl-2 and c-erbB-2) and p53 in proliferative, hyperplastic, and malignant
      endometrium.
AB  - BACKGROUND: The various morphological groupings of endometrial pathology are
      often difficult to distinguish from each other. The endometrium is an actively
      proliferating tissue and there is an overlap in cell proliferation fraction (CPF)
      between benign proliferative endometrium (BPE) and endometrial carcinoma (EC).
      Apoptosis in benign cycling endometrium is related to the menstrual cycle. In
      this study we evaluated CPF, apoptosis, and oncogenes that relate to cell
      turnover (bcl-2, p53, and c-erbB-2) in the spectrum of endometrial pathology.
      METHODS: We examined a total of 64 cases consisting of 10 cases of BPE, 18 cases
      of simple endometrial hyperplasia (SEH), 18 cases of complex hyperplasia (CEH;
      including eight cases with atypical hyperplasia), and 18 cases of EC, FIGO grade
      1. CPF was measured by the mitotic index (MI) and by the percentage of Ki-67
      positive nuclei (Ki-67 index). Apoptotic index (AI) was determined on hematoxylin
      and eosin sections. RESULTS: MI was 2.48% in BPE, 0.65% in SEH, 0.6% in CEH, and
      0.91% in EC (P < .00001). Ki-67 index was 38.44%, 16.4%, 23.25%, and 31.7%
      respectively (P < .00001). AI was 1.17%, 2.2%, 2.57%, and 3.31% respectively (P =
      .02). The AI/MI and AI/Ki-67 ratios were lowest in BPE and highest in SEH (P =
      .007). All cases of BPE, 84% of SEH cases, 77% of CEH cases, and 88% of EC cases
      displayed cytoplasmic and/or nuclear bcl-2 expression. Cytoplasmic bcl-2
      expression increased from BPE to SEH, whereas it decreased in CEH and EC with
      emergence of only nuclear expression. Of the EC cases, 38.8% showed intense
      nuclear bcl-2 reactivity and a significantly higher Ki-67 index than cases with
      cytoplasmic expression (P = .01). No p53 or c-erbB-2 expression was seen in
      either BPE or EH. Of the EC cases, 50% were positive for p53 whereas 30% were
      positive for c-erbB-2. C-erbB-2-positive cases had a significantly higher Ki-67
      index and AI than negative cases (P = .02). Cases of EC with p53 expression also
      had significantly higher AI (P = .01). CONCLUSIONS: In actively proliferating
      tissues like endometrium, CPF does not correlate with progression to malignancy.
      In contrast, AI and derived AI/CPF ratios are better indicators of progression.
      The expression of p53, c-erbB-2, and nuclear bcl-2 in EC correlate with higher
      cell turnover indices (CPF and AI).

PMID- 9781658
TI  - Microsatellite instability in endometrial carcinomas: clinicopathologic
      correlations in a series of 42 cases.
AB  - Instability at microsatellite repeat sequences (MI) has been observed in
      endometrial carcinomas (EC) arising sporadically or in association with the
      hereditary colon cancer syndrome. However, the clinical and pathological features
      of the EC with MI have not been characterized. DNA of 42 patients with EC was
      extracted from blood and from fresh-frozen and paraffin-embedded tumor tissue.
      Microsatellite loci on chromosomes 4, 5, 10, 12, 17, and 18 were amplified by
      polymerase chain reaction. MI was defined by a mobility shift in the tumor DNA as
      compared with normal DNA. Results were correlated with the clinical and
      pathological features of the tumors. MI at three or more loci was detected in 12
      of 42 cases (28%). There were no significant differences between EC with and
      without MI with regard to age of presentation, stage, evidence of estrogenic
      stimulation, mucinous differentiation, estrogen receptor, c-erbB2, or p53
      immunostaining. However, MI was more frequent in endometrioid (11/33, 33.3%) than
      in nonendometrioid (1/9, 11%) carcinomas. Only one papillary serous carcinomas
      showed MI. MI was found in one of two cases of endometrial hyperplasia adjacent
      to EC. It was concluded that MI is a common genetic abnormality of endometrial
      carcinoma and appears to be more frequent in endometrioid than in nonendometrioid
      tumors.

PMID- 9781659
TI  - Spontaneous duodenal-caval fistula with embolization of intestinal contents.
AB  - We describe the second example of a duodenal-caval fistula in a patient with
      peptic ulcer disease. This condition was complicated by embolization of
      intestinal contents to the lung, with abundant intravascular mucin. This is the
      first histological documentation of intravascular mucin apart from amniotic fluid
      embolism. It is well known that mucin may activate coagulation. We propose that
      intravascular mucin activated the coagulation cascade in our patient, causing
      disseminated intravascular coagulation and adult respiratory distress syndrome.

PMID- 9781660
TI  - An endodermal sinus tumor arising from a mature cystic teratoma in the
      retroperitoneum in a child: is a mature teratoma a premalignant condition?
AB  - We herein report an 18-month-old girl who presented with a retroperitoneal mature
      teratoma that later developed into an endodermal sinus tumor. Her symptoms
      included an expanding abdominal girth. The serum levels of alpha-fetoprotein were
      moderately elevated. The excised specimen was a benign mature cystic
      retroperitoneal teratoma measuring 18 x 11 x 8 cm in size. A hemorrhagic focus
      measuring 4 cm in diameter was present, which proved to be the focus of an
      endodermal sinus tumor histologically. The retroperitoneal mature teratoma
      observed in this case showed malignant germ-cell differentiation. The above case
      is thought to be extremely rare, but these findings also suggest the possibility
      of a mature teratoma presenting as a premalignant condition. The sequence of
      "mature teratoma--germ-cell malignancy" is thus considered to represent a new
      potential pattern of early phase of carcinogenesis in teratomas.

PMID- 9781661
TI  - Familial amyloidotic polyneuropathy type I with extracellular superoxide
      dismutase mutation: a case report.
AB  - We report an autopsy case of familial amyloidotic polyneuropathy (FAP) Type I
      with mutations in both transthyretin (TTR) and extracellular superoxide dismutase
      (EC-SOD). This patient started to develop peripheral neuropathy at age 25,
      followed by cardiac, renal, and autonomic nervous system failure due to massive
      amyloid deposition. Thirteen years after the initial symptoms, he died of septic
      shock. Autopsy revealed suppurative peritonitis, multiple abscesses in the bile
      ducts and urinary tract, and more marked amyloid deposition than commonly seen in
      FAP. Amyloid deposition occurred in various organs and tissues, especially
      prominently around blood vessels and in interstitial tissues, and was
      demonstrated immunohistochemically to be composed of TTR but not amyloid A (AA)
      and not amyloid L (AL) proteins. The serum EC-SOD content of the patient was 10
      fold higher than those seen often in other FAP patients and in healthy controls.
      Genetic analysis demonstrated the single amino acid substitutions in Val30Met TIR
      and Arg213Gly EC-SOD. Since these data suggest the dissociation of EC-SOD from
      the vascular wall, massive amyloid deposition in the present case may be related
      to increased oxidative stress in loco.

PMID- 9781662
TI  - Pathology of the malignant colorectal polyp.

PMID- 9781663
TI  - Intraepithelial and stromal dendritic cells in human choroid plexus.

PMID- 9781664
TI  - Human papillomavirus infection in esophageal squamous cell carcinoma in Belgium.

PMID- 9781665
TI  - p120 immunoexpression in neoplastic tissues.

PMID- 9781666
TI  - The promoter of human p22/PACAP response gene 1 (PRG1) contains functional
      binding sites for the p53 tumor suppressor and for NFkappaB.
AB  - We describe functional binding sites for the tumor suppressor p53 and for
      NFkappaB residing in the promoter of the novel human early response gene p22/PRG1
      (IEX-1/DIF-2). Gel shift and supershift assays demonstrate binding of p53 and
      NFkappaB to their corresponding sites in vitro. CAT-reporter gene assays show
      transactivation of the human p22/PRG1 promoter by p53 in Hep3B cells stably
      transfected with a temperature-sensitive mutant p53, but not in p53-deficient
      Hep3B cells. TNF alpha induced NFkappaB dependent transactivation was shown in
      HepG2 cells or in 818-4 pancreatic cancer cells. These data imply that human
      p22/PRG1 is a target gene for p53 and NFkappaB involved in growth regulation and
      stress response.

PMID- 9781667
TI  - DT-diaphorase catalyzes N-denitration and redox cycling of tetryl.
AB  - Rat liver DT-diaphorase (EC 1.6.99.2) catalyzed reductive N-denitration of tetryl
      (2,4,6-tri-nitrophenyl-N-methylnitramine) and 2,4-dinitrophenyl-N
      methylnitramine, oxidizing the excess of NADPH. The reactions were accompanied by
      oxygen consumption and superoxide dismutase-sensitive reduction of added
      cytochrome c and reductive release of Fe2+ from ferritin. Quantitatively, the
      reactions of DT-diaphorase proceeded like single-electron reductive N-denitration
      of tetryl by ferredoxin:NADP+ reductase (EC 1.18.1.2) (Shah, M.M. and Spain, J.C.
      (1996) Biochem. Biophys. Res. Commun. 220, 563-568), which was additionally
      checked up in this work. Thus, although reductive N-denitration of nitrophenyl-N
      nitramines is a net two-electron (hydride) transfer process, DT-diaphorase
      catalyzed the reaction in a single-electron way. These data point out the
      possibility of single-electron transfer steps during obligatory two-electron
      (hydride) reduction of quinones and nitroaromatics by DT-diaphorase.

PMID- 9781668
TI  - Monomeric bovine beta-lactoglobulin adopts a beta-barrel fold at pH 2.
AB  - We have determined a crude structure of the apo form of bovine beta
      lactoglobulin, a protein of 162 amino acid residues with a molecular mass of 18
      kDa, at a low pH on the basis of data collected using only homonuclear 1H NMR
      spectroscopy. An ensemble of protein conformations was calculated with the
      distance-geometry algorithm for NMR applications (DYANA). The monomeric protein
      at low pH adopts a beta-barrel fold, well-superimposable on the structure
      determined by X-ray crystallography for the dimer at physiological pH. NMR
      evidence suggests the presence of disordered loop regions and terminal segments.
      Structural differences between the monomer at pH 2 and the dimer at pH 7,
      obtained by X-ray crystallography, are discussed, paying particular attention to
      surface electrostatic properties, in view of the high charge state of the protein
      at low pH.

PMID- 9781669
TI  - Enhanced fMLP-stimulated chemotaxis in human neutrophils from individuals
      carrying the G protein beta3 subunit 825 T-allele.
AB  - We have recently described a C825T polymorphism in the gene encoding for the
      Gbeta3 subunit of heterotrimeric G proteins. The 825T allele is associated with a
      novel splice variant (Gbeta3-s) and enhanced signal transduction via pertussis
      toxin (PTX)-sensitive G proteins. fMLP-induced chemotaxis, but not O2-
      generation, was increased in neutrophils with the TC/TT (EC50 = 1.5 +/- 1.3 nM)
      genotypes compared to the CC genotype (EC50 = 5.9 +/- 1.5 nM). Maximal fMLP
      induced increase in [Ca2+]i was significantly reduced in neutrophils from
      individuals with TC/TT genotype vs. CC genotype (212.9 +/- 10.1 nM vs. 146.4 +/-
      24.2 nM). Gbeta3-s appears to be associated with enhanced immune cell function in
      humans.

PMID- 9781670
TI  - Purification and characterization of the 3-chloro-4-hydroxy-phenylacetate
      reductive dehalogenase of Desulfitobacterium hafniense.
AB  - The membrane-bound 3-chloro-4-hydroxyphenylacetate (Cl-OHPA) reductive
      dehalogenase from the chlorophenol-reducing anaerobe Desulfitobacterium hafniense
      was purified 11.3-fold to apparent homogeneity in the presence of the detergent
      CHAPS. The purified dehalogenase catalyzed the reductive dechlorination of Cl
      OHPA to 4-hydroxyphenylacetate with reduced methyl viologen as the electron donor
      at a specific activity of 103.2 nkat/mg protein. SDS-PAGE revealed a single
      protein band with an apparent molecular mass of 46.5 kDa. The enzyme contained
      0.68 +/- 0.2 mol corrinoid, 12.0 +/- 0.7 mol iron, and 13.0 +/- 0.7 mol acid
      labile sulfur per mol subunit. The N-terminal amino acid sequence of the enzyme
      was determined and no significant similarity was found to any protein present in
      the gene bank.

PMID- 9781671
TI  - Contribution of a PS1-like element to the tissue- and cell-specific expression of
      the human GLP-1 receptor gene.
AB  - The GLP-1 receptor (GLP-1R) mediates the insulinotropic effects of the incretion
      hormone glucagon-like peptide 1 (7-36) amide (GLP-1). Recently, we cloned the 5'
      flanking region of the human GLP-1R gene. To characterize tissue- and cell
      specific cis-regulatory elements, we constructed a series of 5'-deletions of the
      promoter. The activity of these constructs was tested in different cell lines. An
      element with high homology to PS1 was found to repress GLP-1R promoter activity
      in fibroblasts and pancreatic D-cells, but was not active in pancreatic A- and B
      cells. PS1 was described to inhibit activation of a D-cell-specific enhancer.
      Cloning the PS1-like element upstream a heterologous promoter (SV40) revealed
      that it is functionally active independently from this enhancer. Our data suggest
      that basal activity of the GLP-1R promoter is silenced in a tissue- and cell
      specific manner by negatively acting cis-regulatory elements, including a PS1
      like element.

PMID- 9781672
TI  - Differential activity of a variant form of the human Id-1 protein generated by
      alternative splicing.
AB  - Members of the Id family of helix-loop-helix proteins are ubiquitously expressed
      and dimerize with members of the class A and class B basic helix-loop-helix
      proteins. Due to the absence of a basic region, Id proteins act as dominant
      negative antagonists of basic helix-loop-helix transcription factors, which
      regulate cell growth and differentiation in diverse cell types. Recent findings
      suggest that the functions of Id proteins are well regulated at both the
      transcriptional level and the post-transcriptional level. We show here that the
      alternative splicing variant of human Id-1 protein possesses a different binding
      specificity for basic helix-loop-helix transcription factors and is expressed in
      a cell cycle-dependent manner. Therefore, alternative splicing of Id-1 could
      provide a post-transcriptional mechanism to regulate Id-1 function.

PMID- 9781673
TI  - Modifications outside the proteinase binding loop in Cucurbita maxima trypsin
      inhibitor III (CMTI-III) analogues change the binding energy with bovine beta
      trypsin.
AB  - Five 26-peptide analogues of the trypsin inhibitor [Pro18]CMTI-III containing Leu
      or Tyr in position 7 and Val or Tyr in position 27: 1 (Leu7, Tyr27), 2 (Tyr7,
      Val27), 3 (Tyr7, Tyr27), 4 (Leu7, Val27) and 5 (Leu7, Ala18, Tyr27) were
      synthesized by the solid-phase method. Analogues 1-4 displayed Ka with bovine
      beta-trypsin of the same order of magnitude as the wild CMTI-III inhibitor,
      whereas for analogue 5, this value was lower by about 3 orders of magnitude. This
      indicated that for the analogues with Pro (but not with Ala) in position 18, the
      side-chain interactions between positions 7 and 27 did not play a critical role
      for the stabilization of the active structure. In addition, these results also
      suggest that Tyr7 is involved in an additional aromatic interaction with position
      41 of the enzyme.

PMID- 9781674
TI  - Preparation of basal cell membranes for scanning probe microscopy.
AB  - Scanning probe microscopy has the potential for investigating membranes in a
      physiological environment. We prepared with a lysis-squirting protocol basal cell
      membranes, that are suitable for scanning probe microscopy. Investigations using
      atomic force microscopy under liquid revealed cellular filaments which correlated
      perfectly with fluorescently stained actin filaments. Globular structures with a
      diameter as little as 10 nm could be resolved by stripping cytoplasmic components
      from the membranes. Therefore, cytoplasmic sides of supported basal cell
      membranes prove useful to gain high resolution with scanning probe microscopy in
      studies of plasma membrane associated structures and processes under buffer
      solution.

PMID- 9781675
TI  - Impaired glucose sensing by intrahepatic, muscarinic nerves for an insulin
      stimulated hepatic glucose uptake in streptozotocin-diabetic rats.
AB  - Insulin-induced net hepatic glucose uptake depends on the sensing by muscarinic,
      intrahepatic nerves of a glucose concentration gradient between portal vein and
      hepatic artery. The function of these intrahepatic nerves was examined in
      streptozotocin-diabetic rats. In the presence of the glucose gradient insulin
      induced net glucose uptake in isolated perfused livers from control and acutely
      diabetic but not from chronically diabetic animals. The neurotransmitter
      acetylcholine still mimicked the existence of the gradient, excluding a metabolic
      impairment of livers of chronically diabetic animals. The impairment of the
      intrahepatic nerves due to diabetic neuropathy could contribute to postprandial
      hyperglycemia in diabetes mellitus.

PMID- 9781676
TI  - 2D-isolation of pure plasma and thylakoid membranes from the cyanobacterium
      Synechocystis sp. PCC 6803.
AB  - Aqueous polymer two-phase partitioning in combination with sucrose density
      centrifugation offered, for the first time, a 2D-separation method for the
      isolation of pure plasma and thylakoid membranes from the cyanobacterium
      Synechocystis 6803 without any cross-contaminations. The purity of the membrane
      fractions was verified by immunoblot analysis using antibodies against membrane
      specific marker proteins. As an initiation of a proteomics project, two prominent
      proteins, which were observed only in the plasma membrane (Slr1513, a
      hypothetical protein, and HofG, a general secretion pathway protein), or in the
      thylakoid membrane (PsaE, a photosystem I protein, and NdhH, a subunit of NADH
      dehydrogenase), were identified.

PMID- 9781677
TI  - phd1+, a histone deacetylase gene of Schizosaccharomyces pombe, is required for
      the meiotic cell cycle and resistance to trichostatin A.
AB  - A gene named phd1+ encoding a protein highly homologous to the yeast and human
      histone deacetylases, such as Saccharomyces cerevisiae Rpd3p and human HDAC1, was
      cloned from Schizosaccharomyces pombe. The immune complex isolated from S. pombe
      cells expressing Phd1 fused to the FLAG epitope showed histone deacetylase
      activity, which was inhibited by trichostatin A (TSA), a specific inhibitor of
      histone deacetylase. The null mutation of phd1+ resulted in a marked decrease in
      the total cellular histone deacetylase activity and an increase in the
      sensitivity to TSA. Although the phd1 disruptant showed no obvious defect in the
      mitotic cell cycle or mating, both homothallic haploid and heterothallic diploid
      cells failed to form spores in the absence of phd1+. These results indicate that
      phd1+ encodes a histone deacetylase, which is involved in the meiotic cell cycle
      in S. pombe.

PMID- 9781678
TI  - Collagen type XVI expression is modulated by basic fibroblast growth factor and
      transforming growth factor-beta.
AB  - We investigated the effects of bFGF and TGF-beta on the expression of type XVI
      collagen, a member of the fibril associated collagen family, in human dermal
      fibroblasts and arterial smooth muscle cells. We found that bFGF decreased the
      alpha1(XVI) collagen mRNA to 18-24% of the controls, while TGF-beta increased the
      mRNA to 150-360%. Immunoprecipitation of metabolically labeled cells revealed
      corresponding, but less pronounced, changes at the protein levels. The results
      suggested that type XVI collagen expression is regulated by bFGF and TGF-beta in
      a manner similar to their regulation of the major type I fibrillar collagen
      produced by these cells.

PMID- 9781679
TI  - Characterization of a novel structural member, LukE-LukD, of the bi-component
      staphylococcal leucotoxins family.
AB  - A new member of the staphylococcal bi-component leucotoxins family, LukE (32 kDa)
      and LukD (34.3 kDa) has been characterized from Staphylococcus aureus strain
      Newman. LukE was 58-68% identical with the class S proteins, whereas LukD was 71
      77% identical with the class F proteins of the family. A partial immunoreactivity
      with the various affinity-purified antibodies specific for the other proteins was
      observed. Immunoprecipitation assay and gene probing confirmed a 30% frequency
      among human clinical isolates, differing from the distribution of the other known
      leucotoxins (P<0.005). LukE+LukD was as effective as the Panton-Valentine
      leucocidin for inducing dermonecrosis when injected in the rabbit skin, but not
      hemolytic and poorly leucotoxic compared to other leucotoxins expressed by
      Staphylococcus aureus.

PMID- 9781680
TI  - Hydroxamate derivatives of substrate-analogous peptides containing aminomalonic
      acid are potent inhibitors of matrix metalloproteinases.
AB  - Novel peptides containing the sequence -Pro-Leu-Ama(NHOH)- were synthesized and
      characterized by spectroscopic techniques. Their inhibitory properties towards
      the activated form of native human gelatinase B (MMP-9) and the catalytic domain
      of neutrophil collagenase (cdMMP-8) were determined. The most effective inhibitor
      synthesized exhibits Ki values of 2 x 10(-6) M (cdMMP-8) and 5 x 10(-9) M (MMP-9)
      thus attaining interesting discrimination between the tested metalloproteinases.
      A most important feature of this type of inhibitor is its peptide nature making
      the compounds similar to natural substrates. In spite of the peptide character of
      the inhibitors synthesized, the P1-P1'-peptide bond shows a high resistance to
      cleavage by the proteinases.

PMID- 9781681
TI  - Discrimination of 5'-terminal start codons by translation initiation factor 3 is
      mediated by ribosomal protein S1.
AB  - The interrelation between ribosomal protein S1 and IF3 in
      recognition/discrimination of 5'-terminal start codons by 30S ribosomes has been
      studied using in vitro toeprinting. The study has been performed with two
      naturally occurring leaderless mRNAs, lambda cI and phage r1t rro mRNA, as well
      as with an artificial leaderless mRNA derived from the E. coli ompA gene. We show
      that in the absence of S1, IF3 does not discriminate against the authentic 5'
      terminal start codon of both cI and rro mRNA. Since IF3 was able to exert its
      proofreading function for initiator tRNA(fMet) on 30S ribosomes lacking S1, this
      observation cannot be attributed to a lack of binding to or action of IF3 on 30S(
      S1) ribosomes. In contrast to leaderless mRNAs, ternary complex formation occurs
      in the presence of IF3 with 30S ribosomes when the start codon is preceded by a
      short 20-nucleotide 5'-untranslated region containing a canonical Shine and
      Dalgarno sequence. This suggests that 5'-terminal start codons are recognised by
      IF3 as non-standard because of the lack of 16S rRNA-mRNA contacts.

PMID- 9781682
TI  - TPA and butyrate increase cell sensitivity to the vacuolating toxin of
      Helicobacter pylori.
AB  - The Helicobacter pylori toxin VacA induces large membrane-bound vacuolar
      compartments of late endosomal/lysosomal origin. Pre-treatment of cells with TPA
      and butyrate enhances the toxin induced vacuolisation up to 20 times, depending
      on the cell line, whereas other differentiating factors such as DMSO, EGF,
      valeric and retinoic acid have no effect. The higher toxin sensitivity induced by
      TPA does not result from an increased surface binding or endocytosis. The effect
      of TPA is apparent after several hours from addition and is inhibited by a PKC
      specific inhibitor. These data suggest that expression of cellular proteins,
      other than the toxin receptor(s), influences the vacuolating activity of VacA and
      may contribute to the sensitivity of different cell lines. The present findings
      define the most sensitive in vitro assay of the activity of VacA.

PMID- 9781683
TI  - Characterization of a heavy metal ion transporter in the lysosomal membrane.
AB  - Lysosomes are thought to play a role in various aspects of heavy metal
      metabolism. In the present study we demonstrate for the first time the presence
      of a heavy metal ion transport protein in the lysosomal membrane. Uptake of
      radioactive silver both in highly purified lysosomal membrane vesicles and in
      purified intact lysosomes showed the typical kinetics of a carrier-mediated
      process. This transport was stimulated by ATP hydrolysis, and showed specificity
      for Ag+, Cu2+, and Cd2+. All biochemical properties of this lysosomal metal ion
      transporter could classify it as a heavy metal transporting P-type ATPase. Long
      Evans Cinnamon (LEC) rats, an animal model for the copper transport disorder
      Wilson disease, showed normal lysosomal silver transport.

PMID- 9781684
TI  - Different response to inflammation of the multiple mRNAs of rat N
      acetylglucosaminyltransferase I with variable 5'-untranslated sequences.
AB  - We found that there are at least five subclasses of N
      acetylglucosaminyltransferase I (GnT-I; EC 2.4.1.101) mRNA with different 5'
      untranslated regions in rat brain. These five subclasses were also expressed in
      many tissues with distinct tissue-specific patterns. Moreover, they were
      regulated differently in response to acute-phase inflammation. The expression of
      the most abundant subclass of GnT-I mRNA in rat liver decreased 2.5-fold in
      response to inflammation, concomitantly with a significant decrease in the total
      amount of GnT-I mRNA. In contrast, one of the minor subclasses of GnT-I mRNA was
      induced 10-fold by inflammation.

PMID- 9781685
TI  - Sequence specific cleavage of the HIV-1 coreceptor CCR5 gene by a hammer-head
      ribozyme and a DNA-enzyme: inhibition of the coreceptor function by DNA-enzyme.
AB  - The chemokine receptor CCR5 is used as a major coreceptor for fusion and entry by
      non-syncytia inducing macrophage tropic isolates of HIV-1, which is mainly
      involved in transmission. Individuals who are homozygous for the delta32 allele
      of CCR5 are usually resistant to HIV-1 infection and continue to lead a normal
      healthy life. Thus this gene is dispensable and is, therefore, an attractive
      target in the host cell for interfering specifically with the virus-host
      interaction. With the aim to develop a specific antiviral approach at the
      molecular level, we have synthesized a hammer-head ribozyme and a DNA-enzyme.
      Both ribozyme and DNA-enzyme cleaved the CCR5 RNA in a sequence specific manner.
      This cleavage was protein independent but Mg2+ dependent. The extent of cleavage
      increased with increasing concentration of magnesium chloride. DNA-enzyme was
      more effective in cleaving a full length (1376 bases) in vitro generated
      transcript of CCR5 gene. In this communication, we show that the DNA-enzyme when
      introduced into a mammalian cell, results in decreased CD4-CCR5-gp160 mediated
      fusion of cell membranes. Potential applications of these trans acting molecules
      are discussed.

PMID- 9781686
TI  - The intramolecular electron transfer between copper sites of nitrite reductase: a
      comparison with ascorbate oxidase.
AB  - The intramolecular electron transfer (ET) between the type 1 Cu(I) and the type 2
      Cu(II) sites of Alcaligenes xylosoxidans dissimilatory nitrite reductase (AxNiR)
      has been studied in order to compare it with the analogous process taking place
      in ascorbate oxidase (AO). This internal process is induced following reduction
      of the type 1 Cu(II) by radicals produced by pulse radiolysis. The reversible ET
      reaction proceeds with a rate constant kET = k(1-->2) + k(2-->1) of 450 +/- 30 s(
      1) at pH 7.0 and 298 K. The equilibrium constant K was determined to be 0.7 at
      298 K from which the individual rate constants for the forward and backward
      reactions were calculated to be: k(1-->2) = 185 +/- 12 s(-1) and k(2-->1) 265 +/-
      18 s(-1). The temperature dependence of K allowed us to determine the deltaH(o)
      value of the ET equilibrium to be 12.1 kJ mol(-1). Measurements of the
      temperature dependence of the ET process yielded the following activation
      parameters: forward reaction, deltaH* = 22.7 +/- 3.4 kJ mol(-1) and deltaS* = 
      126 +/- 11 J K(-1) mol(-1); backward reaction, deltaH* = 10.6 +/- 1.7 kJ mol(-1)
      and deltaS* = -164 +/- 15 J K(-1) mol(-1). X-ray crystallographic studies of NiRs
      suggest that the most probable ET pathway linking the two copper sites consists
      of Cys136, which provides the thiolate ligand to the type 1 copper ion, and the
      adjacent His135 residue with its imidazole being one of the ligands to the type 2
      Cu ion. This pathway is essentially identical to that operating between the type
      1 Cu(I) and the trinuclear copper centre in ascorbate oxidase, and the
      characteristics of the internal ET processes of these enzymes are compared. The
      data are consistent with the faster ET observed in nitrite reductase arising from
      a more advantageous entropy of activation when compared with ascorbate oxidase.

PMID- 9781687
TI  - Conformational study of a collagen peptide by 1H NMR spectroscopy: observation of
      the 14N-1H spin-spin coupling of the Arg guanidinium moiety in the triple-helix
      structure.
AB  - CB2, a CNBr peptide of 36 residues from type I collagen alpha1(I) chain has been
      studied by NMR spectroscopy as a function of temperature. At low temperature, the
      guanidinium protons of Arg9 showed sharp 1:1:1 NMR triplets around 6.95 ppm,
      characteristic of 14N coupled protons (1J(NH)=52 Hz) when the quadrupolar
      relaxation rate is drastically reduced. These spectral characteristics and the
      low temperature coefficient of the 1:1:1 triplets (delta delta/delta T of -3.6
      ppb/degrees C) suggest that the H atoms of the protonated guanidinium moiety of
      Arg9 in the triple helix are slowly exchanging with bulk water, most likely
      involved in hydrogen bonds. On the basis of conformational energy computations on
      a model segment of type I collagen (Vitagliano, L., Nemethy, G., Zagari, A. and
      Scheraga, H.A. (1993) Biochemistry 32, 7354-7359), similar to CB2, our data could
      indicate that the guanidinium group of Arg9 form hydrogen bonds with a backbone
      carbonyl of an adjacent chain probably by using the N(epsilon) hydrogen, leaving
      the four N(eta) hydrogens bound to water molecules that must be in slow exchange
      with bulk water and that could therefore be considered structural elements of the
      trimeric alpha1(I) CB2 triple helix. The behaviour of Arg9 has been investigated
      also in terms of equilibrium between random monomer and helical trimer
      conformations controlled by temperature. The thermal unfolding process was found
      to be reversible and the melting point resulted to be 17 degrees C.

PMID- 9781688
TI  - Structure and mutation analysis of the glycogen storage disease type 1b gene.
AB  - Glycogen storage disease (GSD) 1b is the deficiency of endoplasmic reticulum
      glucose-6-phosphate (G6P) transport. We here report the structure of the gene
      encoding a protein likely to be responsible for G6P transport, and its mapping to
      human chromosome 11q23.3. The gene is composed of nine exons spanning a genomic
      region of approximately 4 kb. Primers based on the genomic sequence were used in
      single strand conformation polymorphism (SSCP) analysis and mutations were found
      in six out of seven GSD 1b patients analysed.

PMID- 9781689
TI  - Differential effects of alkaloids on sodium currents of isolated single skeletal
      muscle fibers.
AB  - The effects of the alkaloids ajmaline, lupanine, sparteine, serpentine,
      strychnine, and yohimbine were studied with the loose patch clamp technique on
      sodium currents of isolated single skeletal muscle fibers. The IC50 values for
      half-maximal blocking of the sodium currents were 6.6 microM for ajmaline, 55.7
      microM for quinidine, 168.8 microM for sparteine, and 1.2 mM for lupanine. The
      observed Na+ channel inhibition is in accordance with the use of ajmaline,
      quinidine and sparteine as antiarrhythmic drugs. The interference of alkaloids
      with Na+ channels can also be interpreted as a means to strongly interfere with
      neuronal transmission in herbivores. Alkaloids thus serve as chemical defense
      compounds for the plants producing them.

PMID- 9781690
TI  - Enhancement and inhibition of snake venom phosphodiesterase activity by
      lysophospholipids.
AB  - Lysophospholipids are liberated during venomous action. In this study we
      demonstrated that lysophosphatidyl choline (LPC) of various acyl chains enhances
      considerably the activity of snake venom phosphodiesterase (PDE).
      Lysophosphatidic acid (LPA) and its cyclic form (cLPA), on the other hand, were
      found to inhibit this enzyme in a non-competitive (LPA) or competitive (cLPA)
      manner. Both of these activities may contribute to the progression and subsidence
      of the poisoning profile. PDE from cellular origin was not substantially affected
      by any of the above lysophospholipids.

PMID- 9781691
TI  - A novel photointermediate of octopus rhodopsin activates its G-protein.
AB  - The photointermediate of octopus rhodopsin responsible for G-protein activation
      was examined by a GTPgammaS-binding assay in a reconstituted system with purified
      rhodopsin and photoreceptor G-protein. When octopus rhodopsin alone was incubated
      in the dark after illumination, its ability to stimulate GTPgammaS-binding by the
      G-protein decreased in a time-dependent manner. We associate this decay with the
      decay of a novel photointermediate, transient acid metarhodopsin, which lies
      between mesorhodopsin and acid metarhodopsin. Spectroscopic evidence for its
      existence was suggested by its effects on the turbidity of the vesicles. These
      results suggest that the transient acid metarhodopsin, not the stable final
      photoproduct, acid metarhodopsin, activates a G-protein in octopus
      photoreceptors.

PMID- 9781692
TI  - Factors limiting display of foreign peptides on the major coat protein of
      filamentous bacteriophage capsids and a potential role for leader peptidase.
AB  - Many small peptides can be displayed on every copy of the major coat protein in
      recombinant filamentous bacteriophages but larger peptides can only be
      accommodated in hybrid virions mixed with wild-type protein subunits. A peptide
      insert of 12 residues capable of display at high copy number in a hybrid virion
      was found to be incapable of supporting recombinant virion assembly, a defect
      that could not be overcome by over-expressing leader peptidase in the same
      Escherichia coli cell. In contrast, over-expressing leader peptidase did increase
      the copy number of two 9-residue peptides that were poorly incorporated into
      hybrid virions. The factors that limit peptide display are varied and not
      restricted to the early stages of viral assembly.

PMID- 9781693
TI  - Angiotensinogen cleavage by renin: importance of a structurally constrained N
      terminus.
AB  - Angiotensinogen, a plasma serpin, functions as a donor of the decapeptide
      angiotensin I, which is cleaved from the N-terminus by renin. To assess the
      contribution of the serpin framework to peptide cleavage we produced a chimaeric
      molecule of alpha1-antitrypsin carrying the angiotensinogen N-terminus and
      determined the kinetic parameters for angiotensin I release. The Km for plasma
      angiotensinogen was 18-fold lower than for the chimaeric protein while the
      catalytic efficiency was four-fold higher. We also show that Cys-18 participates
      in a disulphide bond and propose that constraints on the N-terminus profoundly
      affect the interaction with renin.

PMID- 9781694
TI  - Dissection of the cAMP induced cytosolic calcium response in Dictyostelium
      discoideum: the role of cAMP receptor subtypes and G protein subunits.
AB  - The cAMP signaling cascade leading to changes in [Ca2+]i in Dictyostelium
      discoideum was analyzed using cell lines overexpressing single cAMP receptor
      subtypes (cAR1-cAR3) or lacking the G(alpha2) or G(beta) subunit of the G
      protein. Imaging of fura2-dextran-loaded amoebae revealed cAMP-induced [Ca2+]i
      changes characteristic for each receptor subtype activated. Cells expressing
      distinct subtypes sort to defined zones during multicellular development
      suggesting involvement of the specific [Ca2+]i transients in patterning
      processes. Whereas generation of the [Ca2+]i increase was G(alpha2)-independent,
      only few cells devoid of G(beta) displayed a [Ca2+]i change after stimulation
      indicating its participation in the regulation of the calcium homeostasis.

PMID- 9781696
TI  - Widespread occurrence of a highly conserved RING-H2 zinc finger motif in the
      model plant Arabidopsis thaliana.
AB  - Several novel Arabidopsis thaliana proteins containing a RING-H2 zinc finger
      motif were predicted after database searches. Alignment of 29 RING-H2 finger
      sequences shows that the motif is strikingly conserved in otherwise unrelated
      proteins. Only short, non-conserved polar/charged sequences distinguish these
      domains. The RING-H2 domain is most often present in multi-domain structures, a
      number of which are likely to contain a membrane-spanning region or an additional
      zinc finger. However, there are several small (126-200 residues) proteins
      consisting of an N-terminal domain, rich in aliphatic residues, and a C-terminal
      RING-H2 domain. Reverse-transcription PCR suggests that the RING-H2 genes are
      widely expressed at low levels.

PMID- 9781695
TI  - Escherichia coli SecA shape and dimensions.
AB  - SecA shape and conformational flexibility in solution were studied by small angle
      X-ray scattering. Dimeric SecA is a very elongated molecule, 15 nm long and 8 nm
      wide. SecA is therefore four times as long as the membrane is wide. The two
      globular protomers are distinctly separated and share limited surface of
      intermolecular contacts. ATP, ADP or adenylyl-imidodiphosphate (AMP-PNP) binding
      does not alter the SecA radius of gyration. A SecA mutant that catalyzes multiple
      rounds of ATP hydrolysis does not undergo conformational changes detectable by
      small angle X-ray scattering (SAXS). We conclude that SecA conformational
      alterations observed biochemically during nucleotide interaction are only small
      scale and localized. The ramifications of these findings on SecA/SecYEG
      interaction are discussed.

PMID- 9781697
TI  - In vivo phosphorylation of poly(ADP-ribose) polymerase is independent of its
      activation.
AB  - Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme, which is activated by DNA
      strand breaks. Although PARP is known to be cleaved by the cysteine protease,
      caspase-3/CPP32, during apoptosis, signal cascade which regulates the PARP
      activity has not been fully understood. In this study, we investigated post
      translational modification of PARP. We found that PARP was phosphorylated by a
      serine kinase in vivo. PARP was activated temporarily and extensive auto
      modification occurred on PARP, possibly by the fragmented DNA during apoptosis
      induced by etoposide in Jurkat cells. However, the phosphorylation level was not
      changed for up to 6 h, after PARP cleavage began in apoptosis by the treatment
      with etoposide. Furthermore, we showed the presence of a PARP-associated kinase
      in nuclear extracts of the HTLV-I infected T-cell lines but not in uninfected T
      cell lines, whereas this kinase did not inhibit the PARP activity even in the
      presence of ATP. Taken together, in vivo phosphorylation of PARP might be
      independent of the activation or cleavage of PARP.

PMID- 9781698
TI  - Biochemical and spectroscopic characterization of catechol oxidase from sweet
      potatoes (Ipomoea batatas) containing a type-3 dicopper center.
AB  - Two catechol oxidases have been isolated from sweet potatoes (Ipomoea batatas)
      and purified to homogeneity. The two isozymes have been characterized by EXAFS,
      EPR-, UV/Vis-spectroscopy, isoelectric focusing, and MALDI-MS and have been shown
      to contain a dinuclear copper center. Both are monomers with a molecular mass of
      39 kDa and 40 kDa, respectively. Substrate specificity and NH2-terminal sequences
      have been determined. EXAFS data for the 39 kDa enzyme reveal a coordination
      number of four for each Cu in the resting form and suggest a Cu(II)-Cu(II)
      distance of 2.9 A for the native met form and 3.8 A for the oxy form.

PMID- 9781699
TI  - An examination of the selective tissue tension scheme, with evidence for the
      concept of a capsular pattern of the knee.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to examine whether there is
      evidence to support 2 elements of the passive-range-of-motion (PROM) portion of
      Cyriax's selective tissue tension scheme for patients with knee dysfunction: a
      capsular pattern of motion restriction and the pain-resistance sequence.
      SUBJECTS: One hundred fifty-two subjects with unilateral knee dysfunction
      participated. The subjects had a mean age of 40.0 years (SD=15.9, range=13-82).
      METHODS: Passive range of motion of the knee and the relationship between the
      onset of pain and resistance to PROM (pain-resistance sequence) were measured,
      and 4 tests for inflammation were used. Interrater reliability was assessed on 35
      subjects. RESULTS: Kappa values for the individual inflammatory tests ranged from
      .21 to .66 for categorization of the joint as inflamed, based on at least 2
      positive inflammatory tests (kappa=.76). Reliability of PROM measurements was
      indicated by intraclass correlation coefficients of .72 to .97. Reliability of
      measurements of the pain-resistance sequence was indicated by a weighted kappa of
      .28. A capsular pattern, defined as a ratio of loss of extension to loss of
      flexion during PROM of between 0.03 and 0.50, was more likely than a noncapsular
      pattern in patients with an inflamed knee or osteoarthrosis (likelihood
      ratio=3.2). An association was found between a capsular pattern and arthrosis or
      arthritis. CONCLUSION AND DISCUSSION: These findings provide evidence to support
      the concept of a capsular pattern of motion restriction in persons with inflamed
      knees or evidence of osteoarthrosis.

PMID- 9781700
TI  - Comparison of two outcome measures for infants with cerebral palsy and infants
      with motor delays.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to compare the Gross Motor
      Function Measure (GMFM) and the Peabody Developmental Gross Motor Scale (PDMS-GM)
      as measures of change in infants with cerebr-al palsy (CP) and infants with motor
      delays. We hypothesized that mean change scores would be greater for the GMFM
      than for the PDMS-GM. SUBJECTS AND METHODS: Subjects were 42 infants with a mean
      adjusted age of 13.9 months (SD=6.1, range=4.2-24.2). Twenty-four infants had CP,
      and 18 infants had motor delays. The GMFM and the PDMS-GM were administered to
      the infants 3 times over a 6-month period. Raw scores were standardized for data
      analysis. Data were analyzed using a 3-factor repeated-measures analysis of
      variance. RESULTS: For the 6-month period, mean PDMS-GM age-equivalent scores
      increased 3.8 months and mean scaled scores increased 35 points for infants with
      motor delays compared with increased scores of 1.8 months and 13 points for
      infants with CP. Mean GMFM scores increased by 12.2% for infants with rmotor
      delays and by 4.2% for infants with CP. The diagnosis X time interaction was
      significant. Infants with motor delays had a greater change in motor development
      compared with the infants with CP. The hypothesis that the GMFM is more
      responsive to change than the PDMS-GM was not supported. CONCLUSION AND
      DISCUSSION: The findings suggest that the GMFM and the PDMS-GM are comparable in
      measuring change in infants with CP or motor delays. Implications for selection
      and use of either measure are discussed.

PMID- 9781701
TI  - The effect of professional education on the knowledge and attitudes of physical
      therapist and occupational therapist students about acquired immunodeficiency
      syndrome.
AB  - BACKGROUND AND PURPOSE: Anxiety and fear about caring for people with acquired
      immunodeficiency syndrome (AIDS) are concerns expressed by students in health
      care professions. This study was designed to evaluate the influence of education
      offered to physical therapist (PT) and occupational therapist (OT) students on
      their knowledge, attitudes, and willingness to provide services to people with
      AIDS. SUBJECTS AND METHODS: Twenty-six undergraduate PT students and 23
      undergraduate OT students completed a questionnaire at the beginning of their
      professional education program, following a 5-hour AIDS education seminar, and
      shortly before their graduation. The questionnaire consisted of 3 subscales
      designed to evaluate the respondents' knowledge, attitudes, and willingness to
      treat people with AIDS. RESULTS: At the time of graduation, the students in both
      disciplines showed improvement in knowledge about AIDS (14.3% for PT students and
      13.8% for OT students) and more positive attitudes toward people with AIDS (7.4%
      for PT students and 5% for OT students). In both disciplines, the students'
      willingness to provide services for people with AIDS remained unchanged following
      the AIDS education seminar and at the end of the professional education program.
      CONCLUSION AND DISCUSSION: The professional education offered to the cohort of
      students in this study appeared to be beneficial in improving their knowledge and
      attitudes toward people with AIDS, but it did not affect their willingness to
      work with this patient group.

PMID- 9781703
TI  - The interrater reliability of force measurements using a modified
      sphygmomanometer in elderly subjects.
AB  - BACKGROUND AND PURPOSE: Physical therapists working with elderly people require
      an instrument that provides reliable force measurements and can be used in a
      clinical setting. The modified sphygmomanometer has been identified as
      potentially fulfilling these requirements, yet there is an absence of research on
      the reliability of measurements taken with this instrument on elderly patients.
      This study was undertaken to investigate the interrater reliability of force
      measurements, in a group of elderly subjects, using a modified sphygmomanometer.
      SUBJECTS: Thirty-six hospitalized subjects (mean age=75.28 years, SD=9.43,
      range=62-95) participated in the study. METHODS: With the modified
      sphygmomanometer, 3 examiners evaluated the isometric force of the elbow
      extensors and hip extensors using a break test and a make test, respectively.
      RESULTS: Intraclass correlation coefficients (2,1) reflecting reliability were
      .87 for the elbow extensors and .65 for the hip extensors. The estimation of the
      components of variance for hip extensors revealed that these results were due in
      part to the raters but that random error contributed to a much larger extent.
      CONCLUSION AND DISCUSSION: The modified sphygmomanometer appears to be practical
      to use, and the high correlations found in this study for the elbow extensors
      suggest that reliable measurements can be obtained with this instrument. Further
      research is needed, however, to specify the manner in which the modified
      sphygmomanometer can be used when assessing different muscle groups.

PMID- 9781702
TI  - Variability in spatiotemporal gait characteristics over the course of the L-dopa
      cycle in people with advanced Parkinson disease .
AB  - BACKGROUND AND PURPOSE: Understanding the nature and extent of fluctuations in
      spatial and temporal variables of gait (eg, speed, stride length [SL], stride
      time [ST]) over the course of the levodopa (L-dopa) cycle of individuals with
      advanced Parkinson disease (PD) is important in order to assess patients and
      examine the effectiveness of interventions. The purpose of this study was to
      determine whether gait variables are sufficiently stable to be used as outcome
      measures in a clinical trial involving patients with advanced PD. SUBJECTS: Five
      volunteers (3 male, 2 female; mean age=67.8 years; Hoehn and Yahr stages 3-4)
      with idiopathic PD of a mean duration of 15.0 years participated. METHODS: Gait
      speed, SL, and ST were measured as the subjects walked 7.2 m at self-selected
      speeds. To evaluate the full "on-off" sequence of the L-dopa response, this
      analysis was repeated 11 times, at intervals of 10% of the L-dopa cycle. Each
      subject was analyzed on 3 separate days, with approximately 1 month between
      tests. Two-way repeated-measures analyses of covariance, with 2 within-subject
      factors (percentage of L-dopa cycle and day) and 1 covariate (height), were
      applied, and coefficients of variation were calculated to determine the extent of
      change in speed, SL, and ST over the L-dopa cycle and over the 3 days. RESULTS:
      The subjects' overall mean gait speed was 70.39 cm/s, representing 55.4% of the
      age-related normative values. There were no effects of percentage of the L-dopa
      cycle or day or of the interaction of percentage of the L-dopa cycle and day on
      speed, SL, and ST. The coefficients of variation for speed and SL were
      consistently higher than the normative values, ranging from 13.5% to 23.8% and
      from 13.9% to 23.3% at 20% of the L-dopa cycle, respectively. CONCLUSION AND
      DISCUSSION: When interpreting spatiotemporal measurements of gait of patients
      with advanced PD, fluctuations can be extensive and may not follow a predictable
      pattern.

PMID- 9781704
TI  - Treatment of leg edema and wounds in a patient with severe musculoskeletal
      injuries.
AB  - This case report describes the application of a technique for the treatment of
      leg edema and wounds resulting from a severe distal tibiofibular fracture.
      Following injury and numerous fracture- and wound-related surgeries in the first
      year postinjury, this patient developed leg edema, required daily treatment of 2
      leg wounds, and was unable to wear a shoe due to foot swelling. He was referred
      to the physical therapy clinic 1 year postinjury for ankle rehabilitation and to
      diminish the leg edema. Therapy consisting of manual lymph drainage, compressive
      bandaging, exercise, and skin care was provided for 7 weeks. A compression
      stocking was issued near the end of treatment, which the patient continued to
      wear daily thereafter. At the time of discharge from therapy, the leg edema had
      decreased 74% and the wound area of both wounds had decreased 89%. Improvements
      continued following discharge. By 10 weeks after the start of treatment, edema
      had decreased 80.9%, one wound had healed, and the second wound was 93% improved.
      The patient was able to wear a shoe and resume recreational activities. This case
      report provides insight into a treatment that may shorten rehabilitation and
      control the cost of caring for injuries complicated by prolonged edema.

PMID- 9781705
TI  - Constructive dialogue.

PMID- 9781706
TI  - An alternative way to display SF-36 results for individual patients.

PMID- 9781707
TI  - More on the DPT.

PMID- 9781708
TI  - Results of the Multidisciplinary Critical Care Knowledge Assessment Program,
      1998.

PMID- 9781709
TI  - Dopexamine: much more than a vasoactive agent.

PMID- 9781710
TI  - On the accuracy of intra-arterial pressure measurement: the pressure gradient
      effect.

PMID- 9781711
TI  - Antibodies to TNF-alpha: too little, too late?

PMID- 9781712
TI  - Is there a role for surfactant replacement therapy in adult pulmonary
      dysfunction?

PMID- 9781713
TI  - Fighting fire with fire.

PMID- 9781714
TI  - Acute-phase responses and SIRS/MODS: the good, the bad, and the nebulous.

PMID- 9781715
TI  - Tidal volume, PaCO2, and lung injury.

PMID- 9781716
TI  - Does heliox decrease the need for intubation in acute bronchiolitis?

PMID- 9781717
TI  - Sounding the improvement in outcomes in pediatric critical care: are we listening
      for only what we want to hear?

PMID- 9781718
TI  - An intensivist's dilemma: support of the splanchnic circulation in critical
      illness.

PMID- 9781719
TI  - Dopexamine attenuates endotoxin-induced microcirculatory changes in rat
      mesentery: role of beta2 adrenoceptors.
AB  - OBJECTIVE: To investigate the influence of dopexamine on endotoxin-induced
      leukocyte adherence and on vascular permeability in postcapillary venules of rat
      mesentery. DESIGN: Randomized, controlled trial. SETTING: Experimental
      laboratory. SUBJECTS: Twenty-seven male Wistar rats, weighing 250 to 350 g.
      INTERVENTIONS: Rats received one of three treatments: a) infusion of Escherichia
      coli endotoxin without dopexamine pretreatment; b) infusion of endotoxin with
      dopexamine pretreatment; or c) infusion of endotoxin after pretreatment with
      dopexamine and ICI 118,551, a selective beta2-receptor antagonist. MEASUREMENTS
      AND MAIN RESULTS: Leukocyte adherence, red blood cell velocity, and vessel
      diameters in postcapillary venules were evaluated using in vivo videomicroscopy.
      Vascular permeability was determined by measuring the extravasation of
      fluorescence-labeled albumin. Venular wall shear rate was calculated from red
      cell velocity and vessel diameter. Dopexamine attenuated both the increase in
      leukocyte adherence and vascular permeability during endotoxemia. The attenuating
      effect on leukocyte adherence could not be antagonized by the beta2-adrenoceptor
      antagonist. However, the attenuating effect on vascular permeability was
      antagonized by ICI 118,551. Dopexamine prevented a decrease in venular wall shear
      rate during endotoxemia. This effect was not influenced by ICI 118,551.
      CONCLUSIONS: Dopexamine attenuates endotoxin-induced microcirculatory
      disturbances in rat mesentery. The attenuating effect on vascular permeability is
      a beta2-adrenoceptor-mediated process, whereas the beta2-adrenoceptor actions of
      dopexamine play no significant role in attenuating leukocyte adherence.

PMID- 9781720
TI  - Radial artery pressure monitoring underestimates central arterial pressure during
      vasopressor therapy in critically ill surgical patients.
AB  - OBJECTIVES: Radial artery pressure is known to differ from central arterial
      pressure in normal patients (distal pulse amplification) and in the early
      postcardiopulmonary bypass period. The adequacy of the radial artery as a site
      for blood pressure monitoring in critically ill patients receiving high-dose
      vasopressors has not been carefully examined. DESIGN: Prospective observational
      study comparing simultaneous intra-arterial measurements of radial (peripheral)
      and femoral artery (central) pressures. SETTING: Clinical investigation in a
      university-based surgical intensive care unit. PATIENTS: Fourteen critically ill
      patients with presumed sepsis who received norepinephrine infusions at a rate of
      > or =5 microg/min. INTERVENTIONS: All patients were managed in accordance with
      our standard practice for presumed sepsis, which consisted of intravascular
      volume repletion followed by vasopressor administration titrated to a mean
      arterial pressure of > or =60 mm Hg. MEASUREMENTS AND MAIN RESULTS: Systolic and
      mean arterial pressures were significantly higher when measured from the femoral
      vs. radial site (p < .005). The higher mean arterial pressures enabled an
      immediate reduction in norepinephrine infusions in 11 of the 14 patients. No
      change in cardiac output or pulmonary artery occlusion pressure was noted after
      dose reduction. In the two patients in whom simultaneous recordings were made
      after discontinuation of norepinephrine infusions, equalization of mean arterial
      pressures was observed. CONCLUSIONS: Radial artery pressure underestimates
      central pressure in hypotensive septic patients receiving high-dose vasopressor
      therapy. Clinical management, based on radial pressures, may lead to excessive
      vasopressor administration. Awareness of this phenomena may help minimize adverse
      effects of these potent agents by enabling dosage reduction.

PMID- 9781721
TI  - Effect of a chimeric antibody to tumor necrosis factor-alpha on cytokine and
      physiologic responses in patients with severe sepsis--a randomized, clinical
      trial.
AB  - OBJECTIVES: Tumor necrosis factor (TNF)-alpha appears central to the pathogenesis
      of severe sepsis, but aspects of the cytokine cascade and the link to physiologic
      responses are poorly defined. We hypothesized that a monoclonal antibody to TNF
      alpha given early in the course of severe sepsis would modify the pattern of
      systemic cytokine release and, as a consequence, resuscitation fluid
      requirements, net proteolysis, and hypermetabolism would be reduced. DESIGN:
      Randomized, double-blind, placebo-controlled trial. SETTING: Critical Care Unit
      and University Department of Surgery in a single tertiary care center. PATIENTS:
      Fifty-six patients (from 92 eligible patients) with severe sepsis. Twenty-eight
      patients were randomized to treatment, and were comparable with the placebo group
      for age, gender, race, Acute Physiology and Chronic Health Evaluation II score,
      and site and type of infection. INTERVENTIONS: A 300-mg single dose of cA2 (a
      chimeric neutralizing antibody to TNF-alpha) was given intravenously within 12
      hrs of the onset of severe sepsis. Standard surgical and intensive care therapy
      was otherwise delivered. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of
      TNF-alpha, interleukin (IL)-1beta IL-6, IL-8, IL-10, soluble 75-kilodalton TNF
      alpha receptor (sTNFR-75), and IL-1beta receptor antagonist (IL-1ra) were
      measured by sandwich enzyme-linked immunosorbent assay before cA2 infusion, 8 hrs
      later, and then daily for a minimum of 4 days. Sequential changes in total body
      protein, body water spaces, and resting energy expenditure over 21 days were
      measured, as soon as patients achieved hemodynamic stability, by in vivo neutron
      activation analysis, tritium and bromide dilution, and indirect calorimetry,
      respectively. Twenty-one patients died, ten having received cA2. Suppression of
      measurable TNF-alpha was observed at 8 hrs with subsequent rebound by 24 hrs
      after cA2 treatment. The concentrations of other cytokines were high, were not
      reduced by intervention, and decreased logarithmically over 5 days. Both groups
      reached hemodynamic stability at similar times (57.5 +/- 11.8 hrs in controls vs.
      58.6 +/- 9.2 hrs in the cA2 group) and following similar volumes of infused
      fluids (29.1 +/- 3.4 L vs. 28.9 +/- 4.4 L). No differences in net proteolysis,
      resolution of body water expansion, or alteration in resting energy expenditure
      were demonstrated. CONCLUSION: A single dose of cA2 did not alter the overall
      pattern of cytokine activation or the profound derangements in physiologic
      function that accompany severe sepsis.

PMID- 9781722
TI  - Effect of surfactant on respiratory failure associated with thoracic aneurysm
      surgery.
AB  - OBJECTIVE: To study the effects of surfactant administration on the left lung
      after surgical repair of descending aortic aneurysms on postoperative respiratory
      failure. DESIGN: Randomized, prospective, controlled study. SETTING: Clinical
      investigation. PATIENTS: Eleven patients with respiratory failure associated with
      thoracic aneurysm surgery. INTERVENTION: Eleven adult patients with acute
      respiratory failure (PaO2/FIO2 <300 torr [<40 kPa]) after surgical repair of
      descending aortic aneurysms. The artificial surfactant (30 mg/kg) was given to
      the operated side of the lung by intrabronchial instillation in six patients
      (surfactant group), whereas nothing was instilled in the other five patients
      (control group). MEASUREMENTS AND MAIN RESULTS: Hemodynamic parameters, blood
      gas, and peak inspiratory pressure were measured at the end of surgery, before
      surfactant instillation, and at 2, 6, 12, 24, and 48 hrs after surfactant
      instillation. At the end of surgery, the mean +/- SEM values of the PaO2/FIO2
      ratio were 204 +/- 25 torr (27.2 +/- 3.3 kPa) in the surfactant group and 240 +/-
      26 torr (32.0 +/- 3.5 kPa) in the control group. After 2, 6, 12, and 48 hrs,
      improvements in the PaO2/FIO2 ratios were observed in the surfactant group,
      whereas the control group showed no improvement. Two hours after surfactant
      instillation, the mean value in the PaO2/FIO2 ratio was significantly higher in
      the surfactant group (318 +/- 24 torr [42.4 +/- 3.2 kPa]) (p < .05) compared with
      the control group values (240 +/- 34 torr [32 +/- 4.5 kPa]). CONCLUSION:
      Surfactant administration immediately after surgery restored gas exchange in
      postoperative respiratory failure associated with thoracic aneurysm surgery.

PMID- 9781723
TI  - Influence of angiotensin-converting enzyme inhibitor enalaprilat on endothelial
      derived substances in the critically ill.
AB  - OBJECTIVE: To assess the effects of the angiotensin-converting enzyme inhibitor
      enalaprilat on endothelial cells in septic patients. DESIGN: Prospective,
      randomized, placebo-controlled, blinded study. SETTING: Clinical investigation on
      a surgical intensive care unit of a university hospital. PATIENTS: Forty surgical
      septic patients (noncardiac/nonneurosurgical patients). INTERVENTIONS: After
      inclusion in the study and after baseline data were obtained, either 0.25 mg/hr
      (enalaprilat group, n = 20) or saline solution as placebo (control group, n = 20)
      was continuously given and continued throughout the following 5 days.
      MEASUREMENTS AND MAIN RESULTS: Extensive hemodynamic monitoring was carried out
      in all patients. Plasma concentrations of endothelin-1, angiotensin II, soluble
      thrombomodulin, and 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. All
      measurements were carried out before the start of the infusion ("baseline"
      values) and daily during the following 5 days. All endothelial-derived substances
      (thrombomodulin, endothelin-1, and all soluble adhesion molecules) were similarly
      increased beyond normal in both group. Endothelin-1 increased only in the
      untreated control patients (from 6.9 +/- 0.7 to 14.3 +/- 1.4 mg/mL). Soluble
      thrombomodulin increased in the untreated control patients (from 58 +/- 9 to 79
      +/- 14 ng/mL [p < .05]), but significantly decreased in the enalaprilat-treated
      patients. Soluble adhesion molecules increased in the untreated control group
      (endothelial leukocyte adhesion molecule from 92 +/- 14 to 192 +/- 29 ng/mL;
      intercellular adhesion molecule-1 from 480 +/- 110 to 850 +/- 119 ng/ mL) and
      returned almost to normal values in the enalaprilat patients. The survival rate
      did not differ significantly between the two groups. Control patients developed
      severe sepsis and septic shock more often than the enalaprilat-treated group.
      CONCLUSIONS: The complex pathogenesis of endothelial function abnormalities in
      sepsis may offer a large number of pharmacologic interventions. Administration of
      the angiotensin-converting enzyme inhibitor enalaprilat resulted in a reduced
      release of soluble endothelial-derived substances into the circulating blood,
      which may indicate an improved endothelial function. The specific actions of
      enalaprilat on the endothelium have to be elucidated in further studies.

PMID- 9781724
TI  - APACHE III, unlike APACHE II, predicts posthepatectomy mortality in patients with
      biliary tract carcinoma. Acute Physiology and Chronic Health Evaluation.
AB  - OBJECTIVE: To evaluate Acute Physiology and Chronic Health Evaluation (APACHE) II
      and APACHE III scores after liver resection and to elucidate whether APACHE III
      is more accurate as a predictor of posthepatectomy mortality. DESIGN:
      Retrospective, cohort study. SETTING: Intensive care unit in a tertiary care
      university hospital. PATIENTS: Consecutive series of 101 patients admitted to the
      intensive care unit immediately after elective hepatectomy for biliary tract
      carcinoma. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: APACHE II and
      APACHE III scores were calculated on postoperative days 1, 2, and 3. The 101
      subjects were classified into three groups: a) survivors without posthepatectomy
      liver failure (n = 69); b) survivors with liver failure (n = 17); and c)
      nonsurvivors with liver failure (n = 15). APACHE III, but not APACHE II, was
      significantly different between the three groups at all time points. An increased
      APACHE III score correlated with an increased risk of death, while death did not
      correlate with APACHE II score. CONCLUSION: In posthepatectomy patients with
      biliary tract carcinoma, APACHE III, unlike APACHE II, is sufficiently reliable
      for clinical use to stratify patients and predict mortality.

PMID- 9781725
TI  - Effects of proinflammatory cytokines and bacterial toxins on neutrophil rheologic
      properties.
AB  - OBJECTIVE: To examine the changes in neutrophil deformability, aggregation, and
      adherence in response to stimulation with proinflammatory cytokines and bacterial
      toxins. DESIGN: Prospective, randomized trial. SETTING: Research laboratory.
      SUBJECTS: Neutrophils isolated from healthy volunteers. INTERVENTIONS:
      Neutrophils were exposed to tumor necrosis factor (TNF)-alpha, interleukin (IL)
      1beta, IL-8, their combination, endotoxin (LPS), lipoteichoic acid (LTA), and
      staphyloccocal enterotoxin B (SEB). Neutrophil deformability was measured as
      percent neutrophils filtered through 5-microm diameter filters. Aggregation was
      measured using a platelet aggregometer. Adherence was determined by examining the
      binding of neutrophils to albumin-coated latex beads. MEASUREMENTS AND MAIN
      RESULTS: Exposure to TNF-alpha and IL-1beta led to significant decreases in
      neutrophil filterability, which was attenuated by cytochalasin D pretreatment.
      LPS and LTA also decreased deformability, suggesting that these toxins directly
      stimulated neutrophils independent of cytokines. IL-8 and SEB did not
      significantly affect neutrophil deformability. TNF-alpha and LPS were associated
      with significant neutrophil aggregation, which was inhibited by pretreatment with
      anti-CD18 antibodies. Neutrophil aggregation was not affected by IL-1beta, LTA,
      or SEB. TNF-alpha, IL-8, and LPS increased neutrophil adherence, which also was
      attenuated by pretreatment with anti-CD18 antibodies. IL-1beta, LTA, and SEB did
      not significantly affect neutrophil adherence. CONCLUSIONS: Cytokines and
      bacterial toxins differ in their effects on neutrophil deformability,
      aggregation, and adherence. Of the cytokines examined, TNF-alpha appears to have
      the greatest direct effects on neutrophil rheology. Similarly, endotoxin appears
      to have greater direct effects on neutrophil rheology than the Gram-positive
      bacterial toxins, LTA, and staphylococcal enterotoxins.

PMID- 9781726
TI  - Nitric oxide synthase inhibition and the induction of cytochrome P-450 affect
      heme oxygenase-1 messenger RNA expression after partial hepatectomy and acute
      inflammation in rats.
AB  - OBJECTIVES: a) To evaluate in vivo, in rat liver, heme oxygenase-1 (HO-1)
      messenger RNA (mRNA) expression level and the regulation of 3',5'-cyclic
      guanosine monophosphate (cGMP) production during hepatic regeneration, localized
      inflammation, and systemic inflammation; and b) to investigate the effect of the
      induction of cytochrome P-450 and nitric oxide synthase (NOS) inhibition on HO-1
      mRNA level and cGMP production in the liver. DESIGN: Experimental, comparative
      study. SETTING: Biochemical and molecular biology laboratory. SUBJECTS: Six-wk
      old male Sprague-Dawley rats (n = 60). INTERVENTIONS: We randomly divided the
      rats into four groups: a) saline controls; b) animals receiving
      lipopolysaccharide (600 microg/kg) for systemic inflammation; c) animals
      receiving turpentine oil (5 mL/kg) for localized inflammation obtained by sterile
      abscess; and d) partially hepatectomized animals (two-thirds removal of the
      parenchyma) for hepatic regeneration. MEASUREMENTS AND MAIN RESULTS: Hepatic
      regeneration induced HO-1 mRNA expression, as shown by quantitative reverse
      transcription-polymerase chain reaction analysis. The time course of liver HO-1
      mRNA induction after partial hepatectomy and localized and systemic inflammation
      showed a similar and gradual increase, with a maximum at 6 hrs and a return to a
      minimal level 48 hrs after treatments. Liver HO-1 mRNA was overexpressed during
      localized vs. systemic inflammation. This overexpression was not correlated with
      either serum IL-6 or corticosterone concentrations, but is related to increased
      cGMP production. The administration of phenobarbital, a cytochrome P-450 inducer
      and of nitro-L-arginine methyl ester, a NOS inhibitor, prevented cGMP production
      and abolished the overexpression of HO-1 mRNA. CONCLUSIONS: The results of this
      study indicate that HO-1 mRNA is induced during hepatic regeneration with a
      similar time course to that observed during acute inflammation. In addition, we
      demonstrated that: a) HO-1 mRNA is overexpressed during localized vs. systemic
      inflammation; b) this overexpression is not correlated with IL-6 or
      corticosterone concentrations but is related to intrahepatic cGMP production; c)
      induction of cytochromes P-450 and/or inhibition of NOS both reduce liver cGMP
      production and HO-1 mRNA expression. These results suggest that in rat liver, a
      cGMP-transducing pathway may control HO-1 mRNA expression. Thus, there may be a
      role for HO-1 mRNA in the modulation of the hepatic stress response.

PMID- 9781727
TI  - Extreme hypoventilation reduces ventilator-induced lung injury during ventilation
      with low positive end-expiratory pressure in saline-lavaged rabbits.
AB  - OBJECTIVE: To compare the degrees of ventilator-induced lung injury caused by two
      ventilation protocols. DESIGN: Randomized trial. SETTING: University animal
      laboratory. SUBJECTS: Sixteen New Zealand white rabbits. INTERVENTIONS: After
      five sequential saline lung lavages, eight pairs of anesthetized rabbits were
      allocated randomly to receive either of two ventilation protocols for 4 hrs
      during neuromuscular blockade. Both groups received 3 cm H2O of positive end
      expiratory pressure and 100% oxygen. Control group animals received an estimated
      tidal volume of 12 mL/kg, an inspiratory time of 0.7 sec, and a ventilatory rate
      adjusted for a PaCO2 of 35 to 45 torr (4.7 to 6 kPa). Study group animals were
      ventilated through an intratracheal catheter, with inspiratory time of 1.5 secs,
      ventilatory rate of 20 breaths/min, and peak inspiratory pressure of 4 to 8 cm
      H2O, adjusted to maintain PaCO2 at 150 to 250 torr (20 to 33 kPa). MEASUREMENTS
      AND MAIN RESULTS: Arterial blood gases were measured every 30 mins. After 4 hrs,
      a final lung lavage was performed. Physiologic parameters, cell counts and
      protein concentration in the final lavage, and lung histology were compared
      between groups. The alveolar-arterial oxygen tension gradient was higher in the
      study group over the first 1.5 hrs, but the time profile showed significantly (p
      = .001) greater improvement in the study group. After 4 hrs, the mean alveolar
      arterial oxygen tension gradient was lower in the study group (94 torr [12.5 kPa]
      vs. 201 torr [26.8 kPa]). The increase in neutrophil count from the initial to
      the final lung lavage was lower in the study group (0.27 x 10(7) cells/L vs. 2.01
      x 10(7) cells/L, p = .037), as was the absolute value of the neutrophil count in
      the final lavage (1.33 x 10(7) cells/L vs. 3.02 x 10(7) cells/L, p = .04). The
      median hyaline membrane score was lower in the study group (0.5 vs. 3.0) but the
      difference was not statistically significant. CONCLUSION: These findings suggest
      that a very low tidal volume reduces ventilator-induced lung injury in saline
      lavaged rabbits during ventilation at low lung volume.

PMID- 9781728
TI  - Liver as a focus of impaired oxygenation and cytokine production in a porcine
      model of endotoxicosis.
AB  - OBJECTIVES: To determine whether the liver is a focus of insufficient oxygenation
      and whether liver is a source of tumor necrosis factor (TNF) and interleukin-6
      (IL-6) in a porcine model of endotoxicosis. DESIGN: In vivo, prospective,
      controlled, repeated-measures, experimental study. SETTING: Experimental
      physiology laboratory in a university. SUBJECTS: Juvenile pigs, weighing 22 to 35
      kg. INTERVENTIONS: Catheters for blood sampling were inserted into the carotid
      artery, portal vein, hepatic vein, and pulmonary artery of anesthetized animals.
      Ultrasonic flow probes were placed on the portal vein and the hepatic artery.
      During surgery, normal saline was infused intravenously at 25 mL/kg/hr. Following
      stabilization, animals were allocated randomly to one of two groups. The
      endotoxemic group (n = 6) received 50 mg/kg of purified Escherichia coli
      lipopolysaccharide infused into the external jugular vein over 1 hr. The control
      group (n = 6) received a sham saline infusion infused over 1 hr. Once the
      endotoxin or sham infusion was initiated, the rate of the intravenous saline
      infusion was increased to 48 mL/kg/hr for the remainder of the experiment.
      Measurements were obtained before the endotoxin or sham infusion, immediately
      after the infusion, and every 30 mins thereafter for 4 hrs. MEASUREMENTS AND MAIN
      RESULTS: Blood gases, lactate, and bioactive TNF and IL-6 concentrations were
      measured from the carotid artery, portal vein, hepatic vein, and pulmonary
      artery. The porcine model is characterized by systemic hypotension, pulmonary
      hypertension, and maintenance of cardiac output. Despite decreased hepatic oxygen
      delivery in endotoxemic animals (p < .02), there was no change in hepatic oxygen
      consumption compared with controls. Throughout the experiment, there was net
      hepatic consumption of lactate in both groups. There was no significant hepatic
      production (or consumption) of TNF or IL-6 in either group. CONCLUSIONS: In this
      porcine model of endotoxicosis, there is a reduction of hepatic oxygen delivery
      but dysoxia is not present. The liver is not a source of TNF or IL-6 in this
      model of endotoxicosis.

PMID- 9781729
TI  - Partial liquid ventilation reduces pulmonary neutrophil accumulation in an
      experimental model of systemic endotoxemia and acute lung injury.
AB  - OBJECTIVE: To determine whether pulmonary neutrophil sequestration and lung
      injury are affected by partial liquid ventilation with perfluorocarbon in a model
      of acute lung injury (ALI). DESIGN: A prospective, controlled, in vivo animal
      laboratory study. SETTING: An animal research facility of a health sciences
      university. SUBJECTS: Forty-one New Zealand White rabbits. INTERVENTIONS: Mature
      New Zealand White rabbits were anesthetized and instrumented with a tracheostomy
      and vascular catheters. Animals were assigned to receive partial liquid
      ventilation (PLV, n = 15) with perflubron (18 mL/kg via endotracheal tube),
      conventional mechanical ventilation (CMV, n = 15) or high-frequency oscillatory
      ventilation (HFOV, n = 5). Animals were ventilated, using an FIO2 of 1.0, and
      ventilatory settings were required to achieve a normal PaCO2. Animals were then
      given 0.9 mg/kg of Escherichia coli endotoxin intravenously over 30 mins. Partial
      liquid ventilation, conventional mechanical ventilation, or high-frequency
      oscillatory ventilation was continued for an additional 4 hrs before the animals
      were killed. A group of animals not challenged with endotoxin underwent
      conventional ventilation for 4.5 hrs, serving as the control group (control, n =
      6). Lungs were removed and samples were frozen at -70 degrees C. Representative
      samples were stained for histology. A visual count of neutrophils per high-power
      field (hpf) was performed in five randomly selected fields per sample in a
      blinded fashion by light microscopy. Lung samples were homogenized in triplicate
      in phosphate buffer, ultrasonified, freeze-thawed, and clarified by
      centrifugation. Supernatants were analyzed for myeloperoxidase (MPO) activity by
      spectrophotometry with o-dianisidine dihydrochloride and hydrogen peroxide at 460
      nm. MEASUREMENTS AND MAIN RESULTS: Histologic analysis of lung tissue obtained
      from control animals showed normal lung architecture. Specimens from the PLV and
      HFOV groups showed a marked decrease in alveolar proteinaceous fluid, pulmonary
      vascular congestion, edema, necrotic cell debris, and gross inflammatory
      infiltration when compared with the CMV group. Light microscopy of lung samples
      of animals supported with PLV and HFOV had significantly lower neutrophil counts
      when compared with CMV (PLV, 4 +/- 0.3 neutrophils/hpf; HFOV, 4 +/- 0.5
      neutrophils/hpf; CMV, 10 +/- 0.9 neutrophils/hpf; p < .01). In addition, MPO
      activity from lung extracts of PLV and HFOV animals was significantly lower than
      that of CMV animals (PLV, 61 +/- 13.3 units of MPO activity/lung/kg; HFOV, 43.3
      +/- 6.8 units of MPO activity/lung/kg; CMV, 140 +/- 28.5 units of MPO
      activity/lung/kg; p < .01). MPO activity from lungs of uninjured control animals
      was significantly lower than that of animals in the PLV, HFOV, and CMV groups
      (control, 2.2 +/- 2 units of MPO activity/lung/kg; p < .001). CONCLUSIONS:
      Partial liquid ventilation decreases pulmonary neutrophil accumulation, as shown
      by decreased neutrophil counts and MPO activity, in an experimental animal model
      of ALI induced by systemic endotoxemia. The attenuation in pulmonary leukostasis
      in animals treated with PLV is equivalent to that obtained by a ventilation
      strategy that targets lung recruitment, such as HFOV.

PMID- 9781730
TI  - Neutrophil accumulation is reduced during partial liquid ventilation.
AB  - OBJECTIVE: This study evaluates the ability of perflubron to inhibit pulmonary
      neutrophil accumulation during partial liquid ventilation (PLV) in the setting of
      acute lung injury. DESIGN: Randomized, controlled, nonblinded study. SETTING:
      Research laboratory at a university. SUBJECTS: Male, Sprague-Dawley rats (n =
      120, 506 +/- 42 g). INTERVENTIONS: Animals were divided into eight groups (n = 15
      in each group, of which n = 12 for myeloperoxidase content and n = 3 for
      histologic neutrophil counting): a) GV-CVF group, animals received gas
      ventilation (GV) with the induction of lung injury using cobra venom factor
      (CVF); b) PLV-CVF group, animals received partial liquid ventilation before the
      induction of lung injury; c) PEEP-CVF group, animals received positive end
      expiratory pressure (PEEP) before the administration of cobra venom factor; d)
      CVF-PLV group, animals received partial liquid ventilation after cobra venom
      factor; e) CVF-PEEP group, animals received PEEP after cobra venom factor; f) PLV
      only group, animals received partial liquid ventilation only; g) GV only group,
      animals received gas ventilation only; and h) NVSBA group, nonventilated
      spontaneous breathing animals. MEASUREMENTS AND MAIN RESULTS: After the
      experimental period, total lung myeloperoxidase content was significantly
      decreased in the PLV-CVF (0.29 +/- 0.08, p = .02) and PEEP-CVF (0.34 +/- 0.04, p
      = .01) groups when compared with the GV-CVF group (0.62 +/- 0.07). When compared
      with the GV-CVF group, a trend toward a reduction in myeloperoxidase was observed
      in the CVF-PLV (0.42 +/- 0.05, p = .07) and the CVF-PEEP (0.39 +/- 0.06, p = .07)
      groups. When compared with the cobra venom factor only group (GV-CVF 47 +/- 2
      neutrophils/high-power field), reductions in neutrophil count were observed in
      all groups (neutrophils/high-power field): PLV-CVF (20 +/- 2, p = .009); PEEP-CVF
      (24 +/- 1, p = .01); CVF-PLV (30 +/- 2, p = .03); and CVF-PEEP (37 +/- 1, p =
      .04). CONCLUSION: These data suggest that both partial liquid ventilation and
      PEEP result in a reduction in neutrophil accumulation in the setting of acute
      lung injury.

PMID- 9781731
TI  - Hypocapnia does not alter hepatic blood flow or oxygen consumption in patients
      with head injury.
AB  - OBJECTIVE: To evaluate the effects of hypocapnia on the systemic and hepatic
      circulations and oxygenation values in patients with head injury. DESIGN: Open
      label, prospective study. SETTING: University hospital, department of
      anesthesiology and intensive care unit. PATIENTS: Eleven mechanically ventilated
      patients with isolated head trauma and stable hemodynamic status. INTERVENTIONS:
      At the beginning of the study, each patient presented with normocapnic
      ventilation. Mechanical hyperventilation was then adjusted to obtain stable
      hypocapnia over an interval of 24 hrs. Cardiac output and other systemic
      hemodynamic parameters were measured, using a pulmonary artery catheter. Hepatic
      parameters were measured via a catheter inserted into the hepatic vein. Total
      hepatic blood flow was determined by the Fick principle using a continuous
      infusion of indocyanine green. Arterial and hepatic venous blood gases were
      sampled to determine systemic and hepatic-splanchnic oxygenation. Measurements
      were done at the end of the four phases: a) 30 mins of normocapnia (N); b) 30
      mins of hypocapnia (H0); c) 3 hrs of hypocapnia (H3); and d) 24 hrs of hypocapnia
      (H24). Intracranial pressure and cerebral perfusion pressure were hourly
      monitored throughout the study. MEASUREMENTS AND MAIN RESULTS: There were no
      significant changes in systemic hemodynamic parameters. The hepatic blood flow
      index did not differ from normocapnia (N 1.8 +/- 0.4 L/min/m2) to hypocapnia (H0
      1.6 +/- 0.3 L/min/m2; H3 1.7 +/- 0.4 L/min/m2; H24 1.7 +/- 0.4 L/min/m2). The
      ratio of hepatic blood flow index to cardiac index remained stable throughout the
      study. Hypocapnia did not affect hepatic-splanchnic oxygen delivery and
      consumption. CONCLUSIONS: Hypocapnic hyperventilation does not alter hepatic
      hemodynamic parameters in patients with head injury. This result may be related
      to the lack of changes in cardiac output or in the hepatic vasoreactivity.
      Moreover, hypocapnia does not modify hepatic-splanchnic oxygenation. Thus, in
      case of intracranial hypertension, hypocapnia might be used without undesirable
      effect on the hepatic-splanchnic perfusion.

PMID- 9781733
TI  - Differences in pediatric ICU mortality risk over time.
AB  - OBJECTIVES: To compare pediatric intensive care unit (ICU) mortality risk using
      models from two distinct time periods; and to discuss the implications of
      changing mortality risk for severity systems and quality-of-care assessment. DATA
      SOURCES AND SETTING: Consecutive admissions (n = 10,833) from 16 pediatric ICUs
      across the United States that participate in the Pediatric Critical Care Study
      Group were recorded prospectively. Data collection occurred during a 12-mo period
      beginning in January 1993. METHODS: Data collection for the development and
      validation of the original Pediatric Risk of Mortality (PRISM) score occurred
      from 1980 to 1985. The original PRISM coefficients were used to calculate
      mortality probabilities in the current data set. Updated estimates of mortality
      probabilities were calculated, using coefficients from a logistic regression
      analysis using the original PRISM variable set. Quality-of-care tests were
      performed using standardized mortality ratios. RESULTS: Risk of mortality from
      pediatric ICU admission improved considerably between the two periods. Overall,
      the reduction in mortality risk averaged 15% (p < .001). Analysis of mortality
      risk by age indicated a large improvement for younger infants. The mortality risk
      for infants <1 mo improved by 39% (p < .001). Mortality risk improved by 28% (p <
      .001) for infants between 1 and 12 mos. Analysis of mortality risk by principal
      diagnosis indicated substantial improvement in respiratory diseases, including
      respiratory diseases developing in the perinatal period. The mortality risk for
      respiratory diseases improved by 45% (p < .001). The improvement in mortality
      risk substantially deteriorated the calibration of the original PRISM severity
      system (p < .001). As a result of changing mortality risk, the standardized
      mortality ratios across the 16 pediatric ICUs demonstrated substantial
      disparities, depending on the choice of models. CONCLUSIONS: This study documents
      differences in pediatric ICU risk of mortality over time that are consistent with
      a general improvement in the quality of pediatric intensive care. Despite
      continued widespread use of the original PRISM, recent improvements in pediatric
      ICU quality of care have negated its usefulness for many intended applications,
      including quality-of-care assessment.

PMID- 9781732
TI  - Helium-oxygen improves Clinical Asthma Scores in children with acute
      bronchiolitis.
AB  - OBJECTIVE: To determine the efficacy of a helium-oxygen mixture in children
      admitted to the pediatric intensive care unit with acute respiratory syncytial
      virus (RSV) bronchiolitis. DESIGN: Randomized, double-blind, controlled,
      crossover study and nonrandomized, prospective study. SETTING: A pediatric
      intensive care unit in a university hospital. PATIENTS: Nonintubated children
      with signs of acute lower respiratory tract infection and a positive rapid
      immunoassay for RSV admitted to the pediatric intensive care unit. INTERVENTIONS:
      Treatment with either helium-oxygen or air-oxygen was administered in random
      order for 20 mins. Nonrandomized patients received helium-oxygen as initial
      therapy. MEASUREMENTS AND MAIN RESULTS: Clinical Asthma Score, respiratory rate,
      heart rate, and pulse oximetry oxygen saturation values were recorded at baseline
      (before randomization) and at the end of each 20-min treatment period (helium
      oxygen or air-oxygen). Nonrandomized patients were studied 20 mins into helium
      oxygen delivery. Eighteen patients were studied, 13 of whom were randomized. Five
      children with severe bronchiolitis (Clinical Asthma Score of > or =6) were
      initially given helium-oxygen and scored at 20 mins. Mean Clinical Asthma Score
      was 3.04 (range 1 to 7.5) in the 13 randomized patients and 4.25 (range 1 to 9)
      in the 18 patients overall. Clinical Asthma Score decreased in the 13 randomized
      patients (mean 0.46, p < .05) and in the 18 patients overall (mean 1.23, p < .01)
      during helium-oxygen delivery. In randomized patients with Clinical Asthma Scores
      of <6 (n = 12), a positive correlation (rs = .72) was observed between the
      Clinical Asthma Score at baseline and the change in Clinical Asthma Score during
      helium-oxygen administration (p = .009). Respiratory rate and heart rate
      decreased during helium-oxygen treatment but were not statistically significant.
      No complications occurred during helium-oxygen delivery. CONCLUSIONS: Inhaled
      helium-oxygen improves the overall respiratory status of children with acute RSV
      lower respiratory tract infection. In patients with mild-to-moderate
      bronchiolitis (Clinical Asthma Scores of <6), the beneficial effects of helium
      oxygen were most pronounced in children with the greatest degree of respiratory
      compromise.

PMID- 9781734
TI  - Continuous intravenous terbutaline for pediatric status asthmaticus.
AB  - OBJECTIVES: To determine the clinical effects of intravenous terbutaline at >0.4
      microg/kg/min in children with status asthmaticus; to describe the clinical
      findings associated with such therapy, including creatinine phosphokinase
      myocardial band isoenzyme (CPK-MB) concentrations, electrocardiographic
      alterations, and decreased diastolic blood pressure (DBP) with terbutaline usage;
      and to assess the requirement for epinephrine to counteract the decrease in
      diastolic blood pressure. DESIGN: A retrospective review of children admitted
      with status asthmaticus who failed emergency room therapy and required
      intravenous terbutaline. SETTING: San Diego Children's Hospital Pediatric
      Intensive Care Unit. PATIENTS: Eighteen children with status asthmaticus, based
      on clinical and laboratory criteria, between September 1994 and July 1996.
      INTERVENTIONS: Epinephrine was added for below-normal decreases in diastolic
      blood pressure. MEASUREMENTS AND MAIN RESULTS: Continuous monitoring for
      arrhythmias, ST-segment changes, and DBP values during variations in the dose of
      intravenous terbutaline, with or without epinephrine. CPK-MB concentrations were
      determined in 15 of 18 patients. CONCLUSIONS: Intravenous terbutaline was well
      tolerated in asthmatic children for < or =305 continuous hours and at varying
      doses up to a maximum of 10 microg/kg/min. There was no relationship between the
      magnitude of CPK-MB concentrations and the terbutaline or epinephrine doses used.
      Arrhythmias were rare and not related to either terbutaline or epinephrine doses.
      However, ST-segment depression did occur in two patients requiring high-dose
      epinephrine. Terbutaline significantly lowered DBP when used between 0.4 and 1.0
      microg/kg/min, which required epinephrine to be initiated. Epinephrine was not
      required at terbutaline doses of >2 microg/kg/min. There was no mortality.

PMID- 9781736
TI  - Intravenous N-acetylcysteine.

PMID- 9781735
TI  - Effects of vasoactive drugs on gastric intramucosal pH.
AB  - OBJECTIVE: To review current knowledge about the effects of vasoactive agents on
      gastric intramucosal pH (pHi). DATA SOURCES: All studies involving pHi and
      vasoactive agents were retrieved from a computerized MEDLINE search from 1980 to
      1997. We also reviewed the reference lists of all available review articles and
      primary studies to identify references not found in the computerized searches.
      STUDY SELECTION: Clinical and experimental studies using dopamine, dopexamine,
      dobutamine, norepinephrine, epinephrine, nitric oxide, N-acetylcysteine,
      prostaglandins, or pentoxifylline were considered if splanchnic perfusion and/or
      pHi measurements were utilized. DATA EXTRACTION: From the selected studies,
      information was obtained regarding patient population, dosing regimen, duration
      of study, and effects on splanchnic blood flow (SBF), splanchnic oxygenation, and
      pHi. DATA SYNTHESIS: Although dopaminergic effects increase SBF, dopamine does
      not generally increase pHi. Data on the effects of dopexamine on pHi are scarce
      and inconsistent. Dobutamine can significantly increase SBF and usually increases
      pHi. In septic patients, norepinephrine seems to increase pHi. Epinephrine may
      have detrimental effects on gastric perfusion. Prostacyclin seems to increase pHi
      but data are limited. Insufficient evidence exists to support the beneficial
      effects of nitric oxide donors or blockers, pentoxifylline, or N-acetylcysteine
      on pHi. CONCLUSIONS: Overall, the effects of vasoactive agents on pHi are
      unpredictable. Among the catecholamines, dopamine is the least likely, and
      dobutamine the most likely, to increase pHi.

PMID- 9781737
TI  - Pulmonary Artery Catheter Consensus Conference.

PMID- 9781738
TI  - Interpretation of the pulmonary artery occlusion (wedge) pressure: physician's
      knowledge versus the experts' knowledge.

PMID- 9781739
TI  - Haemophilus influenzae in Asia.

PMID- 9781740
TI  - Summary statement: The First International Conference on Haemophilus influenzae
      type b infection in Asia.

PMID- 9781741
TI  - Development, evaluation and implementation of Haemophilus influenzae type b
      vaccines for young children in developing countries: current status and priority
      actions.

PMID- 9781742
TI  - Haemophilus influenzae type b vaccines: history, choice and comparisons.
AB  - The conjugate Haemophilus influenzae type b (Hib) vaccines are safe and far more
      immunogenic among infants and young children than is the unconjugated H.
      influenzae type b polysaccharide. The vaccines differ in their immunogenicity
      when used for primary immunization of infants, and these differences appear to be
      predictive of efficacy, such that some vaccines might be more suitable than
      others in certain populations.

PMID- 9781743
TI  - Haemophilus influenzae type b conjugate vaccines: a review of efficacy data.
AB  - BACKGROUND: The development of a vaccine against Haemophilus influenzae type b
      (Hib) was stimulated by its recognition as a major pathogen of early childhood.
      The first vaccine to be developed was composed of the capsular polysaccharide of
      the organism, polyribosylribitol phosphate (PRP), and although effective in older
      children, it failed to protect those <2 years of age, the group with the highest
      burden of disease. The conjugation of PRP to protein led to a group of vaccines
      with enhanced immunogenicity and the ability to induce immunologic memory and
      thus the potential to protect in infancy. OBJECTIVES: To review the trials of Hib
      conjugate vaccines in which protective efficacy in infants has been assessed and
      the experience in countries in which Hib conjugate vaccines have been introduced
      into the routine infant immunization schedule. DISCUSSION: Each of the Hib
      conjugate vaccines [PRP-diphtheria toxoid conjugate (PRP-D), PRP conjugated to
      outer membrane protein of Neisseria meningitidis group B (PRP-OMP), PRP
      oligosaccharides conjugated to mutant diphtheria toxin CRM197, (HbOC) and PRP
      conjugated to tetanus toxoid (PRP-T)] has been subjected to prospective clinical
      trials and all have demonstrated high protective efficacy with one exception:
      that of the least immunogenic vaccine, PRP-D, when used in a Native American
      population with a high level of natural disease. The trials have used different
      populations and different schedules, which limits conclusions about relative
      efficacies. However, it seems likely that all the vaccines are capable of high
      efficacy in populations with low levels and late age of Hib disease. Three
      vaccines (PRP-D, PRP-OMP, PRP-T) have been tested in populations with high rates
      of disease and only PRP-D has been found lacking. As predicted by immunogenicity
      data, PRP-OMP affords efficacy after one dose, and PRP-T is efficacious with an
      accelerated schedule. Of more practical significance the effectiveness of these
      vaccines when introduced into populations has been uniformly impressive.
      CONCLUSIONS: Particularly where vaccine coverage is high, it is now likely that
      Hib disease can be eliminated using Hib conjugate vaccines in infancy.

PMID- 9781744
TI  - The Gambian Haemophilus influenzae type b vaccine trial: what does it tell us
      about the burden of Haemophilus influenzae type b disease?
AB  - The true burden of disease caused by Haemophilus influenzae type b (Hib) remains
      a mystery in many parts of the developing world. The most frequent manifestations
      of Hib disease are pneumonia and meningitis. In developing countries where it has
      been studied, Hib has proved to be a major cause of infant meningitis, generally
      occurring with greater frequency, in younger infants and with a worse outcome
      than in industrialized countries in the prevaccine era. The burden of Hib
      pneumonia is more difficult to define. Studies from developing countries of
      pneumonia etiology suggested that Hib was responsible for 5 to 10 of episodes of
      severe pneumonia. A Gambian study found Hib to be responsible for 7% of cases.
      However, a recently published trial of a Hib conjugate vaccine in Gambian infants
      showed that the vaccine prevented 21% of episodes of severe pneumonia in vaccine
      recipients, suggesting that this is the true contribution of Hib to the burden of
      severe pneumonia. The same trial demonstrated a mild herd effect, so this figure
      may be an underestimate. The biases that lead to the underestimation of the
      contribution of Hib to the pneumonia burden also apply to estimates of the
      proportion of severe pneumonia caused by Streptococcus pneumoniae. Vaccine trials
      may reveal the true burden of that pathogen also.

PMID- 9781745
TI  - Haemophilus influenzae type b disease and vaccination in Europe: lessons learned.
AB  - OBJECTIVE: To scrutinize the experiences of those European countries that have
      played a central role in understanding the behavior of and vaccination for
      Haemophilus influenzae type b (Hib) diseases, to enlighten weaknesses and to
      explore whether lessons learned would benefit other countries in combating Hib.
      DESIGN: Epidemiologic and clinical data on Hib infections and vaccinations were
      analyzed, including all disease manifestations and all age groups. To improve
      reliability, sources that used active case finding were especially searched for.
      RESULTS: In the prevaccination era meningitis represented 40 to 70% of all
      classical Hib diseases. Epiglottitis was the second most common presentation,
      except in southern Europe (data not available from former socialist countries).
      The overall incidence of meningitis and of all Hib disease combined for children
      ages 0 to 4 years was 23 and 41 per 100000, suggesting 9900 and 17800 cases per
      year, respectively. Including all age groups and entities, >20000 Hib cases
      occurred annually. Vaccination, accomplished with two or three primary doses and
      a late booster, has almost eliminated Hib disease in >10 countries, and >10000
      cases per year are prevented. An age analysis of Hib meningitis suggests that
      strong early immunogenicity is not as imperative in Europe as in some other
      regions. The incidence of non-type b H. influenzae infections has not increased.
      CONCLUSIONS: With Hib epidemiology comparable with that in Europe, good
      protection is achieved by various conjugate vaccines also with two primary doses
      only. However, active research on the whole Hib issue should be a priority,
      especially in southern and eastern European countries.

PMID- 9781746
TI  - Epidemiology of Haemophilus influenzae type b disease and impact of Haemophilus
      influenzae type b conjugate vaccines in the United States and Canada.
AB  - Haemophilus influenzae type b (Hib) was the major cause of invasive bacterial
      disease in the United States and Canada before the introduction of Hib conjugate
      vaccines. Between 10000 and 20000 cases of Hib meningitis and other serious
      diseases occurred each year, leading to death in at least 3% of all patients and
      long term neurologic problems in up to 25% of survivors of meningitis.
      Introduction of Hib conjugate vaccines in Canada and the United States, first in
      children 18 months and older and later as a routine infant immunization,
      dramatically decreased the incidence of disease. By 1995 Hib disease levels had
      declined by more than 95% below preimmunization levels. The remarkably rapid
      reduction in disease incidence was partly because of the ability of the vaccine
      to reduce nasopharyngeal carriage of the organism, leading, when given widely, to
      reduced rates of exposure and infection even in those not immunized. Complete
      elimination of Hib disease in North America, however, will require achievement of
      relatively high coverage rates, especially in hard to reach populations where
      much of the remaining disease is occurring.

PMID- 9781747
TI  - The introduction of Haemophilus influenzae type b immunization into the United
      Kingdom: practical steps to assure success.
AB  - Haemophilus influenzae type b (Hib) vaccine was introduced into the routine
      childhood immunization program in the UK in October, 1992. The implementation was
      coordinated on a national basis, taking account of market research of the
      information needs of both the public and health professionals. Vaccine
      distribution arrangements were linked to the scheduling of children for
      immunization, which was implemented through a national computerized system of
      calling children for immunization. All children commencing immunization were
      called for three doses of Hib vaccine. Children < 1 year of age were called back
      for three doses of vaccine; children >1 but <4 years were called for one dose. No
      boosters were given. National coverage from the outset of the campaign exceeded
      90%; it is now 95% and the incidence of invasive Hib infection has declined by
      >95%. Some of the lessons learned from the UK introduction may be of relevance to
      other countries presently considering the implementation of Hib immunization into
      their routine immunization programs.

PMID- 9781748
TI  - The introduction of routine Haemophilus influenzae type b conjugate vaccine in
      Chile: a framework for evaluating new vaccines in newly industrializing
      countries.
AB  - OBJECTIVE: To determine the burden of Haemophilus influenzae type b (Hib)
      disease, the safety and immunogenicity of Hib conjugate vaccine, the practicality
      of combining Hib conjugate and diphtheria-tetanus-pertussis vaccines and the
      effectiveness of routine vaccination. STUDY DESIGNS: A series of studies were
      carried out involving infants and children in Santiago, Chile. The study designs
      included retrospective surveillance, cost-benefit analysis, randomized placebo
      controlled trials of safety and immunogenicity and a Phase IV postlicensure
      evaluation of vaccine effectiveness. RESULTS: The studies included in this
      stepwise process showed that Hib invasive disease was a significant public health
      problem with a substantial economic burden; that combining Hib conjugate and
      diphtheria-tetanus-pertussis vaccines was practical, safe and elicited a strong
      immunologic response; and that the combined formulation afforded a high level of
      protection against invasive Hib disease (90% effectiveness). CONCLUSIONS: In
      July, 1996, Chile became only the third newly industrializing country to
      introduce routine Hib conjugate vaccination. New vaccines, such as Hib
      conjugates, will be more expensive than existing ones. The stepwise process used
      in Chile may serve as an example for the evaluation of new vaccines in
      nonindustrialized countries.

PMID- 9781749
TI  - Need for Haemophilus influenzae type b vaccination in Asia as evidenced by
      epidemiology of bacterial meningitis.
AB  - OBJECTIVE: To evaluate the role of Haemophilus influenzae type b (Hib) infections
      in Asia by scrutinizing data on Hib meningitis. DESIGN: A comprehensive
      literature search was performed in English and other languages. Special attention
      was paid to the age group of 0 to 4 years, in which the great majority of Hib
      meningitis occurs. RESULTS: Twenty studies from as many countries indicated Hib
      to be a major pathogen in childhood meningitis. In series comprising nearly 2000
      patients, Hib was responsible for at least 50% of cases in one-third of series
      and for at least 25% in three-fourths of series investigated and was the leading
      pathogen overall. The countries in South and Southeast Asia differed from the
      Middle East and East Asia in having a greater incidence of meningitis during the
      first 6 months of life; the proportions were 50 to 60% vs. 10 to 30%,
      respectively (P < 0.001). CONCLUSIONS: Despite lacking data from many areas,
      belief in a paucity of Hib disease in Asia is not supported by the existing data;
      and because meningitis represents only 50 to 75% of all classical Hib
      manifestations and some cases occur after the age of 4 years, vaccination is
      warranted. The cumulative age curves suggest that conjugates with good
      immunogenic potential should be used, especially in South and Southeast Asia.

PMID- 9781750
TI  - An assessment of the value of Haemophilus influenzae type b conjugate vaccine in
      Asia.
AB  - Haemophilus influenzae type b (Hib) is a leading cause of bacterial meningitis
      and pneumonia. Although invasive Hib disease has been reduced substantially
      wherever Hib conjugate vaccines have been introduced into routine childhood
      immunization schedules, these vaccines are more costly compared with the vaccines
      routinely used in the Expanded Program for Immunization. Consequently a model was
      constructed to compare the expected burden of Hib disease with and without a
      national vaccine program for various Asian countries. Cost of the vaccine
      program, expected benefits of reduced deaths and savings from prevented disease
      treatment were assessed for each country based on the model assumptions. Model
      outcomes were expressed as a net cost, cost per death prevented and cost per
      disability-adjusted life year for each country and economic stratum. With the
      assumption of a disease burden of meningitis and pneumonia comparable with that
      observed in other regions, the model predicts that 668000 cases of Hib pneumonia
      and 136000 cases of Hib meningitis would occur annually in this cohort resulting
      in 156000 deaths. Based on current vaccination coverage rates for the individual
      countries, the model predicted that approximately 136000 (87%) Hib deaths could
      be prevented annually with incorporation of Hib vaccine into the Expanded Program
      for Immunization. For each of the countries considered, routine vaccination with
      Hib would cost between 0.1 and 3.0% of per capita gross national product per
      child <5 years of age. Although Hib vaccine would be considered a cost-effective
      public health intervention, it may be cost-prohibitive to implement in the lowest
      income countries without initial donor assistance.

PMID- 9781751
TI  - Study on Haemophilus influenzae type b diseases in China: the past, present and
      future.
AB  - Meningitis caused by Haemophilus influenzae type b (Hib) is a common and serious
      disease for which there now are WHO-certified vaccines that are recommended for
      universal infant immunization in North America and European countries. If these
      vaccines are to be recommended in Asia, it is necessary to know the incidence,
      age distribution and clinical outcome of Hib meningitis and other systemic
      infections in this region. Data on Hib disease in China are scanty. Hib
      meningitis was common during the 1950s in China, accounting for up to 16% of all
      of pyogenic meningitis (up to 38% of cases were caused by unknown pathogens),
      despite severe epidemics of meningococcal meningitis during that period. Since
      1989 we have conducted hospital- and community-based etiologic and epidemiologic
      studies of bacterial meningitis. Hib accounts for 30 to 50% of bacterial
      meningitis in China. The incidence of Hib meningitis in Hefei City was 10.4 per
      100000 children <5 years, a result relatively lower than in the West but higher
      than the rate of 2.7 found in a retrospective study in Hong Kong. Pneumonia is
      the primary cause of death for Chinese children. From 1991 to 1993 the average
      mortality of children<5 years because of pneumonia was 1563.2 per 100000. To
      achieve the goal of reducing the death rate of children by one-third by the year
      2000, greater efforts should be made to reduce the mortality of children with
      pneumonia. Our preliminary study showed that about one-fourth to one-third of
      cases of pneumonia in Chinese children might be caused by Hib. Therefore Hib
      vaccination for infants and children in China might be an effective and valuable
      procedure to achieve the goal.

PMID- 9781753
TI  - Haemophilus influenzae disease in children in India: a hospital perspective.
AB  - We review and summarize published information on diseases caused by Haemophilus
      influenzae in India and unpublished data from our center covering more than three
      decades. Since the mid-1950s H. influenzae has been the most common cause of
      pyogenic meningitis in children admitted to our hospital, accounting for one
      third to one-half of cases. Information from other centers in India has been
      scanty; the lower frequency of isolation of Haemophilus in studies in some
      centers may be caused by unsatisfactory media and culture methods. The annual
      numbers of admissions for pyogenic meningitis in our hospital have been quite
      similar to the numbers of cases of poliomyelitis. Assuming that the similar
      numbers of children hospitalized with these two diseases indicate similar
      incidence rates in the community and taking into account the frequency of
      Haemophilus isolations in pyogenic meningitis, we estimate that there may be as
      many as 75 to 100 cases of meningitis caused by this organism per year per 100000
      children <5 years of age. Although pneumonia caused by H. influenzae has been
      recognized in a few studies, information is too scanty to attempt the estimation
      of incidence. Pus-producing infections caused by Haemophilus are rare.
      Epiglottitis caused by Haemophilus does not seem to occur in India. In recent
      years we have found that most invasive Haemophilus infections are caused by H.
      influenzae type b (Hib); other types or untypable strains are infrequent. An
      increasing prevalence of resistance to chloramphenicol and ampicillin has been
      recognized in our center and elsewhere. Thus from a hospital perspective, primary
      prevention by using Hib vaccine seems to be a rational and beneficial
      intervention. Community-based studies to measure the disease burden of Hib are
      urgently needed for a more satisfactory assessment of the need for, and cost
      benefit of, Hib immunization of all infants.

PMID- 9781752
TI  - Haemophilus influenzae type b infections in Hong Kong.
AB  - A 5-year territory-wide retrospective survey of invasive Haemophilus influenzae
      type b (Hib) diseases in Hong Kong established that the annual incidence for
      children <5 years old was 2.7 per 100000 [95% confidence interval (CI), 2.0 to
      3.5]. However, the corresponding annual incidence in Vietnamese refugees in Hong
      Kong was 42.7 per 100000 (95% CI 17.2 to 87.9), giving a relative risk of 18.5
      (95% CI 8.3 to 41.0). The nasopharyngeal carriage rate of Hib was zero in 621
      healthy Chinese children and 1.3% (95% CI 0.04 to 2.63%) in 300 healthy
      Vietnamese refugees 2 months to 5 years old in Hong Kong. The corresponding
      carriage rate of nontypable H. influenzae was 5.8% (95% CI 1.4 to 7.6%) in
      Chinese and 65.4% (95% CI 58.9 to 69.8) in Vietnamese. In a larger study of 1812
      healthy Chinese children between 6 months and 5 years of age investigated by
      throat swabs, again no Hib was isolated but 141 children (7.8%) were found to be
      carriers of nontype b H. influenzae. In a study of 596 healthy Chinese children
      and adults, 25% had the protective level of anti-Hib antibody of >0.15 microg/ml
      by 1 year and 90% had reached >0.15 microg/ml by 6 years of age. There was some
      evidence that these "natural" antibodies against Hib in Hong Kong Chinese were
      cross-reacting antibodies against antigens on other encapsulated bacteria.

PMID- 9781754
TI  - Invasive Haemophilus influenzae disease in India: a preliminary report of
      prospective multihospital surveillance. IBIS (Invasive Bacterial Infections
      Surveillance) Group.
AB  - OBJECTIVE: To determine the frequency, clinical characteristics and outcome of
      acute invasive infections caused by Haemophilus influenzae. DESIGN: Prospective
      hospital-based surveillance. SETTING: Six large academic referral hospitals in
      India. PARTICIPANTS: Three thousand four hundred forty-one patients from infancy
      to adulthood with pneumonia, meningitis or suspected bacterial sepsis. RESULTS:
      Preliminary data from 24 months of surveillance are presented. There were 58 H.
      influenzae isolates, of which 96% were serotype b. Nearly all isolates were from
      infants and children <5 years old, and most of the childhood isolates were from
      infants <1 year of age. Meningitis cases accounted for 69% of isolates. Overall
      case fatality was 11%. More than 50% of isolates were resistant to
      chloramphenicol, and up to 40% were resistant to ampicillin, trimethoprim
      sulfamethoxazole or erythromycin. There was no resistance to third-generation
      cephalosporins. CONCLUSIONS: These preliminary data from six hospitals suggest a
      substantial burden of severe, preventable H. influenzae infections in India. The
      distribution of clinical syndromes and the ages of our Hib patients are fairly
      similar to data from North America and Europe.

PMID- 9781755
TI  - Epidemiologic study of bacterial meningitis in Jakarta and Tangerang: preliminary
      report.
AB  - OBJECTIVE: To identify the cause of bacterial meningitis in children >1 month of
      age and <5 years of age in several hospitals in Jakarta and Tangerang, Indonesia.
      METHODS: Hospital-based, prospective surveillance study of 100 subjects between 1
      month and 5 years of age. Subjects meeting inclusion criteria were evaluated for
      clinical and laboratory findings of bacterial meningitis. RESULTS: Of 16 subjects
      enrolled thus far, 11 have been diagnosed as bacterial meningitis. Of these 11, 6
      had positive cerebrospinal fluid (CSF) cultures (2 with Haemophilus influenzae
      and one each with Neisseria meningitidis, Staphylococcus aureus, Klebsiella
      ozaenae and Escherichia coli). Three of the 6 had positive latex agglutination
      tests (LAT; 2 H. influenzae and 1 N. meningitidis); LAT was negative for all 10
      with negative CSF culture. CSF Gram-stained smear was positive only for the
      subject with E. coli. CONCLUSIONS: The number of children admitted with bacterial
      meningitis has been declining, perhaps because of early treatment with
      antibiotics in the community. Of culture-positive cases 33% have been caused by
      H. influenzae, but this result is based on few patients thus far. LAT has
      correlated well with culture, whereas Gram stain has had low sensitivity, perhaps
      reflecting deficiencies in technique.

PMID- 9781756
TI  - A population-based survey of Haemophilus influenzae type b nasopharyngeal
      carriage prevalence in Lombok Island, Indonesia.
AB  - BACKGROUND: The Haemophilus influenzae type b (Hib) nasopharyngeal carriage
      prevalence and invasive disease incidence rates are unknown in Indonesia;
      consequently Hib vaccine is not included in the routine vaccine schedule.
      METHODS: To determine carriage prevalence we conducted a population-based, island
      wide prospective study of a systematic sample of 484 children 0 to 2 years of age
      in Lombok, Indonesia. We conducted a risk factor questionnaire and determined
      serotypes and antibiotic sensitivity patterns. RESULTS: We identified 155 H.
      influenzae isolates, of which 22 were type b and 12 were encapsulated but not
      type b. The age- and population-weighted Hib carriage prevalence, adjusted for
      the sampling design, was 4.6% (95% confidence interval, 3.7 to 5.5%). Children
      younger than 6 months of age had a carriage prevalence less than one-half that of
      older children, and carriage varied within the four administrative regions of the
      island; otherwise no risk factors for Hib carriage were identified. All Hib
      specimens were sensitive to ampicillin and 20 (91%) were sensitive to
      chloramphenicol. CONCLUSIONS: The Hib carriage prevalence in Lombok is similar to
      that found in developed countries before vaccine introduction. This suggests that
      further studies should proceed to determine whether Lombok has invasive disease
      rates as high as those that justified vaccine introduction in developed
      countries.

PMID- 9781757
TI  - Childhood bacterial meningitis in Japan.
AB  - Haemophilus influenzae type b (Hib) vaccines currently are not used in Japan, but
      interest in preventing H. influenzae disease by immunization has grown. We
      performed a retrospective survey for bacterial meningitis in 6 prefectures of
      Japan. Questionnaires requested the age, sex, clinical outcome and identity of
      the etiologic organism, if known, of all patients with meningitis younger than 16
      years of age who were admitted during calendar year 1994. Of 876 hospitals within
      the 6 study prefectures, 363 (41.4%) returned a completed questionnaire. There
      were 1769 cases of meningitis reported, of which 160 (9%) were considered
      bacterial in origin. H. influenzae was the most common cause of bacterial
      meningitis, accounting for 68 cases (43%). Sixty-six cases (97%) of H. influenzae
      meningitis occurred in children 4 years of age or younger, and 27 (40%) occurred
      in children <1 year of age. Calculated incidence rates based on the population of
      children 4 years of age or less for each prefecture ranged from 3.4 to 9.9 cases
      per 100000 (mean, 4.7 cases/100000). H. influenzae is the most common cause of
      meningitis in Japan, and the estimated incidence rates from this study are very
      similar to those previously reported from Japan. More comprehensive, prospective
      surveillance studies will be needed to define better the incidence of Hib
      meningitis and to aid in making rational decisions regarding the use of Hib
      vaccination in Japan.

PMID- 9781758
TI  - Epidemiology of systemic Haemophilus influenzae disease in Korean children.
AB  - BACKGROUND: There is a wide variation in the incidence and clinical
      characteristics of invasive infections by Haemophilus influenzae type b (Hib)
      among different populations. Characterizing the clinical significance in a
      particular community is essential for the development of vaccine policy. Data on
      the clinical significance of Hib in Asian children, including epidemiology and
      clinical spectrum, are quite limited. OBJECTIVE: To characterize invasive H.
      influenzae infections in Korean children in terms of clinical spectrum and
      frequency as an etiologic agent of bacterial meningitis and to review literature
      that may be helpful in understanding the epidemiology of H. influenzae disease in
      Far East Asian children, including Koreans. METHODS: Invasive infections by H.
      influenzae, Streptococcus pneumoniae and Neisseria meningitidis diagnosed at the
      Seoul National University Children's Hospital from 1986 to 1996 were reviewed.
      Conventional culture and the latex particle agglutination test were used in
      addition for diagnosis. A detailed literature review was undertaken to trace
      relevant information that may be helpful in understanding the epidemiology of
      invasive Hib disease among Far East Asian children. RESULTS: A total of 169
      invasive infections were identified: 48 H. influenzae; 116 S. pneumoniae; and 5
      N. meningitidis. Of the 48 H. influenzae infections 36 developed in apparently
      healthy children: 25 meningitis; 8 bacteremia; 2 pneumonia; and 1 epiglottitis.
      Forty-four percent of H. influenzae meningitis developed in infants < 1 year of
      age, and 92% occurred in children <5 years of age. H. influenzae was the cause of
      58% of bacterial meningitis in infants and 62% in children <5 years old.
      CONCLUSION: The limited data suggest that the incidence of H. influenzae
      meningitis may be lower in Korean than in US children. Prospective population
      based studies are needed urgently in Asian countries, including Korea.

PMID- 9781759
TI  - Haemophilus influenzae meningitis in Malaysia.
AB  - OBJECTIVE: To determine the pattern of postneonatal childhood meningitis in
      Malaysia. METHODS: Retrospective cross-sectional study involving five pediatric
      departments in Malaysia. RESULTS: There were 435 cases of clinical meningitis
      admitted to the five centers. More than 90% of the patients were <5 years old,
      and one-half were <6 months of age. The estimated overall incidence of childhood
      meningitis in the first 5 years of life was 76.7 per 100000 per year. However, of
      the 435 cases only 71 (16.3%) fulfilled laboratory diagnostic criteria and in
      only 58 of these was an organism isolated. Nearly one-half (48%) of all
      bacteriologically proved cases were caused by Haemophilus influenzae type b
      (Hib). The mortality rate was 12.5% and 21 patients (30%) suffered neurologic
      sequelae. CONCLUSIONS: More than one-half of all cases of culture-positive
      childhood bacterial meningitis were caused by Hib, although successful isolation
      of a pathogen occurred in only a small proportion of cases. For this reason the
      true incidence of Hib meningitis in Malaysia remains unknown. These findings are
      consistent with previous studies in Malaysia.

PMID- 9781760
TI  - Haemophilus influenzae type b disease in Thailand.

PMID- 9781761
TI  - The etiology of bacterial pneumonia and meningitis in Vietnam.
AB  - BACKGROUND: To date no studies on the incidence of Haemophilus influenzae type b
      (Hib) disease, Hib carrier rates in infants and children or the proportion of
      bacterial meningitis cases caused by Hib in Vietnam have been performed. The
      availability of safe and highly effective Hib vaccines makes such information
      important. METHODS: The bacterial etiology of a sample of infants and children
      with pneumonia and meningitis seen at Pediatric Hospital No. 1 in Ho Chi Minh
      City was studied by culture and latex agglutination of blood, cerebrospinal
      fluid, urine and pleural fluid. The carriage rate of pneumococci and Hib was
      studied in a sample of outpatient children. RESULTS: Hib caused 53% of 34 culture
      proven bacterial meningitis cases and pneumococci caused 18%. Of 31 meningitis
      cases diagnosed by latex agglutination, 39% were caused by Hib and 55% by
      pneumococci. Ninety percent of cases of Hib meningitis occurred in children <1
      year of age. Fifty percent of meningitis cases were associated with acute
      respiratory infection. In 213 bacteremic pneumonia cases 92.5% of blood cultures
      grew Streptococcus pneumoniae and only 1% grew Hib. The carrier rate of Hib in
      outpatients <5 years of age with upper respiratory tract infection increased from
      2% to 7.6% between 1993 and 1996. CONCLUSION: Hib is the most frequent cause of
      meningitis in infants and children admitted to hospitals in South Vietnam. Ninety
      percent of Hib meningitis cases occur in patients < 1 year of age. Bacteremic Hib
      pneumonia in Vietnam is rare. The results suggest that Hib is the major cause of
      meningitis in Vietnam but do not permit conclusions regarding its true incidence.
      The carrier rate of Hib in children <5 years of age in Vietnam has increased to
      approximately 7% since 1993.

PMID- 9781762
TI  - The rationale for population-based surveillance for Haemophilus influenzae type b
      meningitis.
AB  - Although Haemophilus influenzae type b (Hib) conjugate vaccines have been
      spectacularly successful, nearly eradicating Hib disease in countries where used
      routinely, they are relatively expensive. In many countries the incidence of
      Haemophilus influenzae type b (Hib) disease is uncertain, and it is unclear
      whether the local burden of Hib disease warrants the costs of adding Hib vaccine
      to the routine immunization program. Population-based surveillance to assess the
      local burden of Hib disease can help decision makers with this process. Although
      pneumonia is more common than meningitis, surveillance for Hib meningitis and
      invasive disease is likely to be more feasible and efficient than surveillance
      for Hib pneumonia. Standardization of laboratory methods for the isolation and
      identification of H. influenzae from CSF specimens is essential to successful
      surveillance. Should a country decide to introduce Hib conjugate vaccine as a
      routine immunization, population-based surveillance data collected before and
      after the introduction of vaccine can be used to monitor its impact. Finally
      population-based surveillance for bacterial meningitis also can provide
      information on the incidence of pneumococcal and meningococcal infections and on
      serogroup or serotype distributions that will be important when evaluating the
      new vaccines for those pathogens that are being developed.

PMID- 9781763
TI  - A nationwide prospective surveillance study in Israel to document pediatric
      invasive infections, with an emphasis on Haemophilus influenzae type b
      infections. Israeli Pediatric Bacteremia and Meningitis Group.
AB  - BACKGROUND AND METHODS: An ongoing nationwide prospective surveillance study was
      initiated in Israel in October, 1988, to document childhood invasive infections
      caused by Haemophilus influenzae type b (Hib), Streptococcus pneumoniae and
      Neisseria meningitidis. This study enabled us to document the effect on childhood
      invasive Hib disease of the introduction of conjugate Hib vaccines to Israel.
      RESULTS: The incidence of invasive Hib disease before the age of 5 years dropped
      from 34 per 100000 before initiation of immunization to < 5 per 100000 in 1995
      and is projected to be <4 in 1996. After <2 years, when various conjugate
      vaccines had been available in the private sector alone and had achieved partial
      coverage only, the Israeli Ministry of Health decided to add Hib conjugate
      vaccine to the regular infant immunization program, free of charge, effective for
      all infants born after January 1, 1994. The vaccine chosen was Hib polysaccharide
      linked to outer membrane protein complex of N. meningitidis B. Vaccine coverage
      has exceeded 90% of all infants born since January 1, 1994. Efficacy and
      effectiveness during the first 34 months of the program (January 1, 1994, to
      October 31, 1996) were 95.4 and 99.7%, respectively, for all invasive Hib disease
      and 97 and 99.4%, respectively, for Hib meningitis. CONCLUSION: The described
      ongoing surveillance program showed the existence and extent of Hib problems in
      Israel and documented the success of the immunization program in essentially
      eliminating the disease in Israel.

PMID- 9781764
TI  - Enhanced surveillance of invasive Haemophilus influenzae disease in England, 1990
      to 1996: impact of conjugate vaccines.
AB  - We report an enhanced prospective survey of invasive Haemophilus influenzae
      infections that has defined the pattern of invasive disease in five English
      regions for 2 years before and 4 years after the introduction of the H.
      influenzae type b (Hib) vaccination program. During the prevaccination period the
      majority of cases of invasive H. influenzae were caused by type b; most (89%) of
      these infections occurred in children <5 years of age and the most common
      presentation was meningitis. Since the introduction of routine immunization of
      infants with conjugate Hib vaccine, there has been a 16-fold reduction in the
      annual attack rate of invasive Hib disease recorded in children <5 years of age.
      This reduction is of a magnitude similar to that observed in other countries with
      Hib vaccination programs. The number of infections caused by non-type b H.
      influenzae has shown a small but progressive increase over the same period,
      emphasizing the need for continued surveillance. There was no increase in the
      number of infections caused by other serotypes. Diagnostic category varied with
      both age and serotype but was not affected by vaccine introduction; meningitis
      was the most common presentation overall but pneumonia and bacteremia were more
      common in adults and with noncapsulated isolates.

PMID- 9781765
TI  - Characterization of immune response as an indicator of Haemophilus influenzae
      type b vaccine efficacy.
AB  - Quantitation of antibodies to Haemophilus influenzae type b (Hib) polysaccharide
      has been an active area of investigation associated with the development of
      polysaccharide and subsequently polysaccharide-protein conjugate vaccines. These
      clinical studies indicate that there are several serologic parameters associated
      with Hib vaccine efficacy in infants. Efficacious vaccines elicit polysaccharide
      specific antibodies in infants; they prime the immune system for an anamnestic
      response; the immune response is long-lived through the period of greatest risk
      for disease; and the elicited antibodies have functional activity as demonstrated
      in bactericidal and opsonophagocytic assays or protection in an infant rat
      challenge model. The immune response to different Hib vaccines varies both
      quantitatively and qualitatively. With the introduction of routine Hib vaccine
      immunization, vaccine performance can rely on these serologic parameters.
      Quantitative serologic assays, the radio-antigen binding and enzyme-linked
      immunosorbent assays, have been developed and standardized. The quality of the
      antigen as well as optimization of all assay steps and reagents are key to
      ensuring specific and reproducible antibody quantitation.

PMID- 9781766
TI  - What is an orthopaedic surgeon in the twenty-first century?

PMID- 9781767
TI  - Publication rates for the scientific sessions of the OTA. Orthopaedic Trauma
      Association.
AB  - OBJECTIVES: To determine the publication rate of the scientific papers presented
      at the Orthopaedic Trauma Association (OTA) meetings from 1990 to 1995 inclusive.
      DESIGN: A Medline search was performed on abstracts presented at the OTA sessions
      from 1990 through 1995 using both authors and key text words within the OTA
      abstract. The publication rate for each meeting, journal of publication, and time
      to publication were tabulated. RESULTS: The publication rate for papers presented
      at the OTA meetings from 1990 through 1994 was 64 percent. This was significantly
      better than publication rates reported for American Academy of Orthopaedic
      Surgeons (AAOS) meetings in 1990 through 1992. The average time to publication
      was sixteen months. The most common journals in which papers derived from the OTA
      abstracts were published include the Journal of Orthopaedic Trauma (JOT), Journal
      of Bone and Joint Surgery combined volumes (JBJS). and Clinical Orthopaedics and
      Related Research (CORR). CONCLUSION: OTA meetings are an excellent source of high
      quality information, which is generally subsequently published in peer-reviewed
      journals. The Journal of Orthopaedic Trauma is the single best source for
      information presented at the OTA meetings. Allowing more papers to be presented
      did not affect the publication rate for the meetings.

PMID- 9781768
TI  - High pressure pulsatile lavage irrigation of intraarticular fractures: effects on
      fracture healing.
AB  - OBJECTIVES: To evaluate the effects of pulsatile lavage and bulb syringe
      irrigation on fracture healing in vivo. DESIGN: Randomized prospective trial in
      an animal model. SETTING: Medical school orthopaedic department. SUBJECTS: Thirty
      New Zealand white rabbits. INTERVENTION: The control group (C) underwent
      osteotomy of the medial femoral condyle, stabilization, and closure. The bulb
      syringe and pulsatile lavage groups underwent the same procedure as group C, with
      the addition of irrigation with one liter of normal saline via a bulb syringe (B)
      or a pulsatile lavage system (P). Animals were administered two fluorescent bone
      stains: xylenol orange at the time of operation, and calcein green one week
      postoperatively. Animals were euthanized two weeks postoperatively and femurs
      were retrieved for histological analysis. MAIN OUTCOME MEASURES: Union was
      determined by examination of microradiographs under light microscopy. The
      viability of bone along the fracture site was determined by evaluation of xylenol
      orange and calcein green staining under fluorescent microscopy. The density of
      new bone formed in the osteotomy site was assessed by computerized digitization
      of standardized regions of the proximal and distal osteotomy. RESULTS: Xylenol
      orange bands were present a mean of 66 +/- 8 percent (mean +/- standard error of
      the mean), 65 +/- 6 percent, and 44 +/- 5 percent of the distance along the
      osteotomy in groups C, B, and P, respectively (p < 0.001). Calcein green bands
      were present throughout the osteotomy site in all specimens. Calcified new bone
      was present in 62 +/- 4 percent, 58 +/- 7 percent, and 41 +/- 9 percent of the
      area measured in groups C, B, and P, respectively (p = 0.07). Twenty percent of
      the osteotomies in groups C and B did not unite, compared with 30 percent in
      group P (p > 0.5). CONCLUSIONS: Pulsatile lavage irrigation of fresh
      intraarticular fractures in rabbits has a detrimental effect on early new bone
      formation; this effect, however, is no longer apparent two weeks following
      irrigation. While this study evaluated the effects of pulsatile lavage irrigation
      in noncontaminated fractures without extensive soft tissue injury, the
      detrimental effects observed on early new bone formation may translate to an
      increased risk of nonunion in the setting of a contaminated open fracture with
      extensive soft tissue injury. Based on the results of this investigation, the
      selective use of pulsatile lavage irrigation appears warranted. In the absence of
      gross wound contamination, irrigation with a bulb syringe appears less likely to
      impair fracture healing than does pulsatile lavage irrigation. Expansion of the
      model used in this study to include bacterial contamination and soft tissue
      crushing may further elucidate the effects of pulsatile lavage irrigation on
      fracture healing.

PMID- 9781769
TI  - Retrograde intramedullary nailing of femoral diaphyseal fractures.
AB  - OBJECTIVES: To prospectively evaluate the results of retrograde intramedullary
      nailing of femoral shaft fractures. DESIGN: Prospective, consecutive series.
      PATIENTS AND SETTING: All patients with a femoral shaft fracture admitted at an
      urban Level 1 trauma center from December 1995 to December 1996 were treated with
      a retrograde femoral intramedullary nail. INTERVENTION: Retrograde femoral
      intramedullary nailing was performed on a radiolucent operating room table.
      Through a three-centimeter medial parapatellar incision, a reamed ten-millimeter
      retrograde nail was inserted. METHODS: From the time of injury until union, the
      following parameters were assessed: operative time, blood loss, extent of
      comminution, open grade, associated injuries, Injury Severity Score, body mass
      index, time to union, secondary procedures, range of motion in the knee. and
      complications. RESULTS: Fifty-seven patients with sixty-one fractures were
      available for follow-up, which averaged 43.1 weeks. Fifty-two percent of
      fractures demonstrated Winquist Type 3 or 4 comminution. Twenty-six percent of
      the fractures were open. Fifty-two fractures healed after the initial nailing,
      five of seven dynamized nails healed, and one patient with bone loss requiring
      bone graft united yielding a final union rate of 95 percent. Of the three
      nonunions (5 percent), two healed with exchange nailing and one remains
      asymptomatic at seventy-one weeks. One patient developed a late septic knee that
      resolved with treatment. Excellent range of motion in the knee was obtained by
      those patients who did not have other ipsilateral limb injuries. CONCLUSIONS:
      This consecutive series had a 95 percent union rate after nailing and
      dynamization as necessary. No knee problems were associated with the retrograde
      femoral intramedullary nailing technique. The one septic knee raises concerns
      about the use of retrograde nailing in severe open femoral shaft fractures.
      Retrograde femoral nailing should be given serious consideration as an
      alternative to antegrade femoral nailing.

PMID- 9781770
TI  - The Essex-Lopresti reduction for calcaneal fractures revisited.
AB  - OBJECTIVES: To evaluate the reduction and outcome of selected intraarticular
      calcaneal fractures treated with percutaneous Essex-Lopresti reduction and
      fixation. DESIGN: Prospective consecutive series. SETTING: Level one trauma
      center and tertiary university hospital. PATIENTS/PARTICIPANTS: Twenty-six
      consecutive patients with an Essex-Lopresti tongue-type, Sanders type 2C
      calcaneus fracture. INTERVENTION: Modified percutaneous Essex-Lopresti type spike
      reduction and fixation of the posterior facet. OUTCOME MEASUREMENTS: Clinical and
      radiographic analysis. METHODS: Twenty-six consecutive patients with calcaneal
      fractures meeting the criteria had an attempted percutaneous reduction performed
      under fluoroscopic control with the patient in the lateral position. Twenty-three
      of the twenty-six feet had an acceptable reduction, and the remaining three were
      treated with open reduction and internal fixation (ORIF). The first seventeen
      cases were stabilized by two Steinmann pins, which were removed at ten to twelve
      weeks. The last six cases were fixed with two cannulated 6.5-millimeter screws,
      which were left in place. Early motion was encouraged in all cases RESULTS: Of
      the twenty-three patients with an acceptable reduction, twenty had no angulation
      between the posterior facet of the talus and the calcaneus and three had <5
      degrees. The tuberosity reduction was <5 degrees in seventeen cases and <10
      degrees in all cases. The calcaneal height was restored to normal in twenty
      cases, and the width (axial view) averaged 119 percent of the contralateral side.
      Follow-up averaged 2.9 years. Using the Maryland foot score there were twelve (55
      percent) excellent, seven (32 percent) good, and three (13 percent) fair results.
      CONCLUSIONS: The Essex-Lopresti spike reduction is a useful method for the
      treatment of tongue-type Sanders type 2C fractures of the calcaneus. Results are
      superior to those in previous series of intraarticular fractures treated with
      ORIF.

PMID- 9781771
TI  - Intraoperative assessment of femoral head vascularity after femoral neck
      fracture.
AB  - OBJECTIVES: To develop an intraoperative technique to predict the development of
      avascular necrosis after internal fixation of femoral neck fractures. DESIGN:
      Prospective study. SETTING: All patients were treated at the same hospital.
      PATIENTS/PARTICIPANTS: Sixty-four patients who presented for internal fixation of
      a femoral neck fracture were enrolled in the study. INTERVENTION: A 2.0
      millimeter drill was used to assess the presence and character of bleeding from
      the femoral head at open reduction and internal fixation of a femoral neck
      fracture. MAIN OUTCOME MEASUREMENTS: Patients were evaluated postoperatively by
      history, examination, and roentgenography for the development of avascular
      necrosis of the femoral head fragment. A minimum two-year follow-up with
      radiography was required for entry into the study, with an average follow-up of
      3.2 years. RESULTS: None of the fifty-six patients with bleeding from the drill
      holes in the femoral head fragment developed avascular necrosis. Eight of eight
      patients with no bleeding after reduction developed avascular necrosis. There
      were no infections or nonunions. CONCLUSIONS: Intraoperative drilling of the
      femoral head is a highly sensitive and specific predictor for the development of
      avascular necrosis after femoral neck fractures.

PMID- 9781772
TI  - High pressure pulsatile lavage of contaminated human tibiae: an in vitro study.
AB  - OBJECTIVE: This study was designed to examine the effect of high pressure
      pulsatile lavage (HPPL) on bone destruction and propagation of bacteria in
      experimentally contaminated human tibiae. METHODS: Using an in vitro model, nine
      human tibiae from above-knee amputations were tested. A mid-diaphyseal tibial
      shaft fracture was created, and each end of the fracture was contaminated with
      bacteria (six tibiae with Staphylococcus aureus, three tibiae with Escherichia
      coli). The proximal end was designated as the control and the distal end was the
      test site. The test site was debrided by HPPL (seventy pounds/square inch, 1,200
      milliliters/minute, 1,050 cycles/minute) with three liters of normal saline,
      whereas the control site did not receive any form of irrigation. Serial sections
      at increasing distance from the fracture site were cultured and the numbers of
      bacterial colony-forming units (CFUs) were determined at each level. The degree
      of macroscopic architectural change in each serial section was graded on an
      ordinal scale. RESULTS: Analysis of culture data revealed a reproducible pattern
      of bacterial propagation into the intramedullary canal. Peak bacterial seeding
      occurred at two to three centimeters from the fracture site (p = 0.023, Wilcoxon
      signed rank test). The degree of bone destruction varied proportionally with the
      depth into the canal and was found to be predictive of the extent of bacterial
      propagation determined by culture data. CONCLUSION: In an in vitro model of a
      contaminated fracture, HPPL resulted in bacterial seeding into the intramedullary
      canal and significant damage to the architecture of the bone. These observations
      might have clinical significance.

PMID- 9781773
TI  - Length of operative procedures: reamed femoral intramedullary nailing performed
      with and without a fracture table.
AB  - OBJECTIVES: To determine whether performing reamed intramedullary nailing of the
      femur without the use of a fracture table decreases the length of operation.
      DESIGN: Retrospective. SETTING: Level 1 trauma center, Nashville. Tennessee.
      PATIENTS/PARTICIPANTS: Consecutively treated patients with fractures of the
      femoral shaft were treated with intramedullary nails from June 1986 to March
      1996. INTERVENTION: Reamed intramedullary nailing of the femoral shaft was
      performed with the use of a fracture table or with the leg draped free on a
      radiolucent table. MAIN OUTCOME MEASUREMENTS: Length of anesthesia time, prep and
      drape time (from the point the anesthetized patient is turned over to the
      surgeons until incision), and intramedullary nailing time (from incision until
      end of surgery) for reamed intramedullary nailing of the femoral shaft performed
      with and without the use of a fracture table were compared. RESULTS: Univariate
      analysis showed statistically significant decreases in the length of prep and
      drape time, operative time, and anesthetic time when fractures were treated
      without the use of a fracture table. Multivariate analysis showed that use of a
      fracture table prolongs prep and drape time (plus twenty minutes), operative time
      (plus seventeen minutes), and anesthesia time (plus seventy-three minutes) when
      the covariates of age, sex, fracture location, learning curve, position of the
      patient, nail brand, and number of distal bolts are controlled. CONCLUSIONS:
      Reamed intramedullary nailing of the femoral shaft performed without the use of a
      fracture table is significantly faster than when the procedure is performed with
      a fracture table.

PMID- 9781774
TI  - Biomechanical comparison of hybrid external fixators.
AB  - OBJECTIVES: To determine the stiffness characteristics of the hybrid ring fixator
      in the treatment of (OTA 41-C) proximal metaphyseal and shaft tibial fractures.
      DESIGN: Five identical composite tibiae were fixed with a Synthes, ACE Fischer,
      Howmedica Monticelli-Spinelli, or Smith & Nephew Trauma Ilizarov hybrid external
      fixator or with the conventional Ilizarov wire fixator. The Synthes and
      Monticelli-Spinelli fixators were tested twice, the first time with the
      connectors on the outside of the ring and the second time with the connectors on
      the inside of the ring. MAIN OUTCOME MEASUREMENTS: A materials testing machine
      was used to apply pure compression, anterior and posterior bending, medial and
      lateral bending, and torsion. Stiffness values were calculated from the load
      deformation and torque angle curves. RESULTS: Overall, the Synthes and Monticelli
      Spinelli fixators were the most rigid of the fixators when the wire-to-ring
      connectors were placed inside the ring. In general, the fixators were stiffest in
      axial compression and least stiff in posterior bending. Wire length had a
      significant effect on overall stiffness. CONCLUSIONS: This study suggests that
      the four hybrid external fixators in standard configuration have stiffness
      characteristics similar to those of the conventional Ilizarov fixator when used
      to treat proximal metaphyseal and shaft fractures of the tibia.

PMID- 9781775
TI  - Enhancement of bone apposition to stainless steel cortical screws by surface
      modification using heat treatment: an experimental study.
AB  - OBJECTIVE: The purpose of the present study was to test whether the surface of
      stainless steel cortical screws modified by an oxidation process (heat treatment)
      resulted in enhancement of bone apposition as a consequence of better bone
      apposition to the metal surface. DESIGN: Control and heat-treated commercial
      cortical screws (stainless steel 316L) were inserted alternately into the tibiae
      of eight goats with a fixed insertion torque. Fluorochrome bone label was given
      during the six-week experimental period, after which the goats were killed and
      the extraction torque force measured. The screws and the adjacent bone were
      processed for histology. MAIN OUTCOME MEASURE: It was hypothesized that the heat
      treated transcortical metal screws would have a greater extraction torque than
      untreated control screws. RESULTS: The extraction torque of the heat-treated
      screws was 0.59 +/- 0.06 newton-meters, which was significantly (p < 0.0001)
      higher (1.7-fold) than that of the control screws (0.35 +/- 0.02 newton-meters).
      Histomorphometric measurements demonstrated a 65 percent, significant (p < 0.05),
      increase in the area of fluorescence (indication of new bone deposition) adjacent
      to the heat-treated implant versus the control screws. CONCLUSIONS: Heat
      treatment of the cortical screws prior to insertion significantly increases
      fixation strength to the host bone in a large animal model. The clinical
      applicability will be to achieve bone apposition similar to that seen with
      titanium implants but with a stiff low-cost material.

PMID- 9781776
TI  - Capacitively coupled electrical stimulation treatment: results from patients with
      failed long bone fracture unions.
AB  - OBJECTIVE: To determine the extent to which capacitively coupled electrical
      stimulation (CCEST) at a long bone fracture site can promote healing of nonunited
      fractures. DESIGN: Sixteen patients with nonunited fractures of nine to seventy
      six months were treated with CCEST. Thirteen patients had previously undergone
      one or more surgical procedures, and the other three had been given plaster
      casts. A sixty-three-kilohertz, six-volt peak-to-peak sine wave signal was
      applied across two forty-millimeter-diameter stainless steel plates placed on the
      skin at opposite sides of the fracture site. The device was used for up to thirty
      weeks until either healing occurred or it was removed after this period and
      considered to have failed. RESULTS: Eleven of the nonunions achieved union at an
      average of fifteen weeks of stimulation. The only significant factor determining
      the success of healing was the distance between the plates; a distance of eighty
      millimeters or less resulted in healing in all cases. Healing was not affected
      significantly by any of the following factors: whether or not the nonunion had
      been treated surgically prior to stimulation, whether or not it had been
      infected, whether or not the patient bore weight after treatment, or by the
      presence or absence of metal at the fracture site from previous surgery.
      CONCLUSIONS: These findings confirm those of previous studies that CCEST promotes
      bone healing of fracture nonunions. The dependence of healing on the interplate
      distance suggests that maintaining sufficient current across the plates is
      necessary to allow healing, which for larger bones may be achieved by increasing
      the area of the plates, the applied voltage, or the excitation frequency of the
      stimulation signal.

PMID- 9781778
TI  - Patient perception of the ischemic arm block.
AB  - OBJECTIVE: To investigate patient perception of the ischemic arm block. DESIGN:
      Retrospective study. SETTING: Fracture clinic of a major city hospital.
      PATIENTS/PARTICIPANTS: One hundred eighty-one consecutive patients who had an
      ischemic arm block were mailed a questionnaire. The response rate was 71 percent.
      RESULTS AND CONCLUSIONS: Forty-two percent of respondents reported significant
      pain from the tourniquet cuff, and 29 percent reported significant pain during
      manipulation or within the first hour after releasing the cuff. Statistical
      analysis showed that cuff pain was independent and not indicative of increased
      individual sensitivity to pain. Manipulation pain was likewise an independent
      phenomenon. There was a close relationship between manipulation pain and
      postprocedure pain. Reported complications were rare. Fourteen percent were
      dissatisfied with the procedure, which correlated with manipulation pain but not
      with cuff pain. In conclusion, significant cuff pain during the procedure is
      common. Manipulation pain is not as common but may lead to dissatisfaction.

PMID- 9781777
TI  - Low-velocity gunshot injuries of the spine with abdominal viscus trauma.
AB  - OBJECTIVE: To evaluate the risk of infection of the spine and associated
      complications after colonic or rectal injury associated with gunshot injury of
      the spine. DESIGN: Retrospective review. SETTING: Presley Memorial Trauma Center,
      Regional Medical Center, Memphis, Tennessee, a statewide Level 1 trauma center.
      PATIENTS: Thirty-three patients with gunshot wounds to the spine and associated
      viscus injury were treated between 1989 and 1994; in thirteen, the bullet passed
      through the colon or rectum before damaging the spine. INTERVENTION: Six patients
      received a single antibiotic (Cefotetan) and seven were given multiple
      antibiotics. Total duration of antibiotic treatment ranged from two to forty
      three days. RESULTS: None of the thirteen patients developed osteomyelitis or
      disc space infection. Most intraabdominal complications were secondary to
      dehiscence of colonic repair. CONCLUSIONS: Because the magnitude of bacterial
      colonization of the vertebrae after colonic injury may not be high, a
      nonoperative approach to treatment of abdominal viscus injuries is appropriate in
      patients with gunshot wounds to the spine. Broad-spectrum antibiotic coverage for
      at least seven days appears to be effective in preventing spinal infection, but
      colonic injuries are associated with an increased incidence of intraabdominal
      abscess and peritonitis.

PMID- 9781779
TI  - Acromion fracture associated with posterior shoulder dislocation.
AB  - We report a case involving combined acromion fracture and posterior glenohumeral
      dislocation. To our knowledge, this combination of injuries has not been reported
      previously in the literature. In our case, the shoulder dislocation was initially
      missed. The utility of additional radiographic views to detect this type of
      injury is emphasized. The mechanism of injury, course of treatment, and clinical
      outcome are presented.

PMID- 9781780
TI  - Volar dislocation of multiple carpometacarpal joints: report of four cases.
AB  - Four acute cases of volar carpometacarpal dislocations of the medial four
      metacarpals were treated in our hospital's emergency room. Our initial diagnosis
      after clinical examination was confirmed by routine x-rays of the hand. Closed
      reduction was followed by percutaneous fixation of the carpometacarpal joints
      with Kirschner wires. Satisfactory function of the hand was obtained in all
      cases.

PMID- 9781781
TI  - Overview and meta-analysis of randomised trials of amiodarone in chronic heart
      failure.
AB  - Unlike other antiarrhythmic class I drugs, amiodarone showed in preliminary
      studies, benefits also in patients with left ventricular dysfunction. These
      positive results have induced the development of large randomised controlled
      studies: their results are reviewed and the controversial points are discussed.
      In a meta-analysis of randomised controlled trials the use of amiodarone in heart
      failure was associated with an approximate 20 to 25% reduction in deaths.
      However, amiodarone was also associated with a 120 to 124% increase in side
      effects.

PMID- 9781782
TI  - Utilisation of transluminal extraction atherectomy in the treatment of saphenous
      vein graft disease: two case reports.
AB  - Saphenous vein graft disease is an increasing problem as more patients undergo
      bypass grafting and to date the most effective management strategy remains
      undefined. The major limitations of angioplasty for saphenous vein graft lesions
      are the risk of distal embolization and restenosis. Primary stenting in this
      situation results in superior lumen enlargement and higher procedural success but
      is still associated with significant restenosis. We describe two cases in which
      transluminal extraction (TEC) atherectomy is utilised for the treatment of vein
      graft disease with good immediate and long term angiographic results. The first
      case reports the use of TEC atherectomy for the primary treatment of a discrete
      eccentric filling defect, and the second case describes the use of this technique
      in the management of in-stent restenosis.

PMID- 9781784
TI  - Improved systolic function after PTCA can be estimated by femoral arterial
      Doppler.
AB  - The effect of coronary angioplasty to the post exertional femoral arterial pulse
      was analyzed in a prospective trial. In 26 patients 30 coronary stenoses could be
      treated. Narrowed lumen diameter dropped from 85.5% +/-8.2 to 34.6% +/-10.7
      (P<0.0001). Patients with a residual coronary artery stenosis of <60% (group A,
      n=15) were compared to those with incomplete revascularisation (stenoses >60%,
      group B, n=11). Post exertional Doppler criteria differed between both groups:
      Peak velocity in group A was 86.08 cm/s +/- 17.8, in group B 72.9 cm/s +/-17,
      mean velocity 32.06 cm/s +/-12.5 versus 23.6 cm/s +/-10.3 acceleration or dV/dt
      813.5 cm/s2 versus 722 cm/s2 +/-164. Statistical significant pre to post
      postexertional findings improved only in group A (P<0.01, peak velocity, P<0.05
      mean velocity and dV/dt). It is concluded that patients with still-existing
      exertional myocardial ischemia can be distinguished from those without
      hemodynamic relevant stenoses by means of a simple noninvasive Doppler analysis
      of femoral arterial pulse.

PMID- 9781783
TI  - Does rheumatic fever occur usually between the ages of 5 and 15 years?
AB  - It has long been considered that rheumatic fever usually occurs in children
      between the ages of 5 and 15 years. However, supporting data from the developing
      countries are insufficient. It is important to know the age of occurrence of
      rheumatic fever for clinical and public health purposes. To describe the age
      distribution of Bangladeshi subjects, we have reviewed the records of all
      patients who attended with acute rheumatic fever in the outpatient department of
      the National Center for Control of Rheumatic Fever and Heart Diseases, Dhaka,
      during June 1990 through November 1995. During this period 630 subjects were
      diagnosed to have acute rheumatic fever defined by the revised Jones criteria. Of
      them, 535 (84.9%) presented with first attack. Their age ranged from 3 to 30
      years, and a skewness to the right of the age distribution was observed. Thus, we
      used percentile distribution to determine reference range of age. The 2.5 and
      97.5 percentiles were 5 and 22 years, respectively. Their mean (standard
      deviation) and median age were 12.7 (4.4) and 12 years, respectively. Slightly
      more than 22% of subjects were older than 15 while less than 1% were younger than
      5 years. This finding was supported by multiethnic data from other developing
      countries. The current analysis warrants reevaluation of the prevailing
      conviction for age of occurrence of rheumatic fever. In conclusion, the age
      reference range for occurrence of rheumatic fever in Bangladesh should be
      considered to be 5 to 22 years but not 5 to 15 years.

PMID- 9781785
TI  - Effect of serum fatty acid composition on coronary atherosclerosis in Japan.
AB  - The serum lipid profiles of patient's with or without significant coronary
      stenosis diagnosed by coronary angiography and of control subjects were compared.
      The level of high-density-lipoprotein cholesterol and eicosapentaenoic acid were
      significantly lower in the patients with significant coronary stenosis than in
      the control subjects. It suggests that high-density-lipoprotein cholesterol and
      omega3 fatty acids may have a protective effect on the progress of coronary
      atherosclerosis. The frequency of eating dark-meat fish was positively associated
      with serum eicosapentaenoic acid and docosahexaenoic acid, omega3 fatty acids,
      and inversely associated with serum stearic acid and linoleic acid. The frequency
      of eating soybean products was positively associated with serum docosahexaenoic
      acid and inversely associated with serum linoleic acid. It is necessary to
      discuss a way to popularise a diet of dark-meat fish and soybean products as a
      means of preventing coronary heart disease.

PMID- 9781786
TI  - Preoperative and early postoperative assessment of the internal thoracic artery
      by transcutaneous duplex ultrasound in coronary artery bypass grafting.
AB  - We examined internal thoracic artery by transcutaneous duplex ultrasound in 26
      patients on four occasions: 4 (+/-2) days before the operation, and 61 (+/-8)
      minutes, 5 days and 53 (+/-3) days postoperatively. There was dominant systolic
      flow in preoperative scans. After the operation a characteristic biphasic flow
      with increased peak diastolic velocity and a decrease in peak systolic/peak
      diastolic velocity ratio was detected in all patients. The pulsed Doppler
      spectrum was used to measure peak velocity, time averaged mean velocity and time
      averaged maximum velocity. Resting internal thoracic artery flows calculated
      using time averaged mean velocity were 30.9+/-5.4 ml/min preoperatively, 40.7+/
      6.3 ml/min immediately after surgery, 41.1+/-8.2 ml/min at 5 days and 40.1+/-4.9
      ml/min at 53 days. There were no significant changes in resting internal thoracic
      artery flow between early and late postoperative studies. Flow estimates
      calculated using 0.5 x time averaged maximum velocity or time averaged mean
      velocity showed good agreement. Early postoperative measurements appear to be a
      good predictor of later resting graft flow.

PMID- 9781788
TI  - The use of an implantable left ventricular assist device in a patient with
      cardiogenic shock following acute myocardial infarction.
AB  - We report the successful long-term use of an implantable left ventricular assist
      device in a 42-year old patient who suffered cardiogenic shock after an acute
      anterior myocardial infarction unresponsive to recanalisation of the infarct
      related artery and intra-aortic balloon counterpulsation. Attempts to wean our
      patient from the assist device were not successful and the patient underwent
      cardiac transplantation after 35 weeks on device assistance. The intermediate and
      long-term use of an implantable left ventricular assist device may be lifesaving
      in post-myocardial infarction cardiogenic shock and may allow sufficient time for
      any stunned myocardium to recover. Should there be no recovery, the device acts
      as a bridge to cardiac transplantation.

PMID- 9781787
TI  - Left atrial appendage function in mitral stenosis: is a group in sinus rhythm at
      risk of thromboembolism?
AB  - OBJECTIVE: To study the left atrial appendage (LAA) function and potential for
      embolization in severe mitral stenosis (MS). BACKGROUND: Patients with MS and
      atrial fibrillation or in sinus rhythm develop systemic emboli. LAA function has
      not been well studied in sinus rhythm. METHODS: Forty consecutive patients with
      MS (valve area < or =0.7 cm2/m2) were studied. LAA ejection fraction and peak
      emptying velocity were measured along with other data. RESULTS: Patients were
      subgrouped according to LAA Doppler flow pattern. Group I (n=13) in sinus rhythm
      had biphasic high velocity > or =25 cm/s. Group II (n=13) in sinus rhythm had
      biphasic low velocity <25 cm/s. Group III (n=14) in atrial fibrillation had
      multiphasic irregular flow <25 cm/s or no definite flow. The LAA ejection
      fraction and peak emptying velocity were strikingly different in all groups. They
      were lower in group II when compared to group I. Group II had intermediate risk
      for thromboembolism compared to Group I and III as judged by systemic
      embolization, spontaneous echo contrast, thrombus in left atrium and LAA.
      CONCLUSION: A subset of mitral stenosis in sinus rhythm at increased risk of
      embolization can be suspected by Doppler transesophageal echocardiographic LAA
      flow profile.

PMID- 9781789
TI  - Effects of exercise position on the ventilatory responses to exercise in chronic
      heart failure.
AB  - OBJECTIVE: Patients with heart failure frequently complain of orthopnoea. The
      objective was to assess the ventilatory response of patients with chronic heart
      failure during erect and supine exercise. DESIGN: Maximal incremental exercise
      testing with metabolic gas exchange measurements in erect and supine positions
      conducted in random order. SETTING: Tertiary referral centre for cardiology.
      PATIENTS: Nine patients with heart failure (aged 61.9+/-6.1 years) and 10 age
      matched controls (63.8+/-4.6). OUTCOME MEASURES: Metabolic gas exchange
      measurements. The slope of the relation between ventilation and carbon dioxide
      production. Ratings of perceived breathlessness during exercise. RESULTS: Oxygen
      consumption (VO2) and ventilation were higher during erect exercise at each stage
      in each group. Peak VO2 was [mean (SD)] 17.12 ml/kg/min (4.07) erect vs 12.92
      (3.61) supine in the patients (P<0.01) and 22.62 (5.03) erect-supine vs 19.16
      (3.78) erect (P<0.01) in the controls. Ratings of perceived exertion were higher
      in the patients at each stage, but unaffected by posture. There was no difference
      in the slope of the relation between ventilation and carbon dioxide production
      between erect and supine exercise 36.39 (6.12) erect vs 38.42 (8.89) supine for
      patients; 30.05 (4.52) vs 28.80 (3.96) for controls. CONCLUSIONS: In this group
      of patients during exercise, there was no change in the perception of
      breathlessness, nor the ventilatory response to carbon dioxide production with
      change in posture, although peak ventilation was greater in the erect position.
      The sensation of breathlessness may be related to the appropriateness of the
      ventilatory response to exertion rather than to the absolute ventilation.

PMID- 9781791
TI  - Predictors of death during 5 years after hospital discharge among patients with a
      suspected acute coronary syndrome with particular emphasis on whether an
      infarction was developed.
AB  - AIM: To describe predictors of death after hospital discharge during 5 years of
      follow-up in a consecutive series of patients surviving hospitalization for
      symptoms and signs of a confirmed or suspected acute coronary syndrome. PATIENTS
      AND METHODS: All patients who between February 15, 1986 and November 9, 1987,
      were hospitalized at Sahlgrenska University Hospital in Goteborg, Sweden, and
      fulfilled the above given criteria. RESULTS: In all, 1948 patients were included
      of whom 731 (38%) had a confirmed acute myocardial infarction (AMI). Independent
      risk indicators for death were: age (P=0.0001); male sex (P=0.005); a history of
      previous AMI (P=0.0001), diabetes mellitus (P=0.003) and smoking (P=0.0001);
      development of AMI during first 3 days in hospital (P=0.0001); in-hospital signs
      of congestive heart failure (P=0.0001); prescription of digitalis (P=0.001) and
      diuretics (P=0.02) at hospital discharge. A history of smoking interacted
      significantly (P=0.02) with the relationship between development of AMI and
      prognosis. Thus, the difference between patients who did and who did not develop
      an AMI was more pronounced among non-smokers than smokers. Other factors which
      interacted significantly with this relationship were a history of angina
      pectoris, and development of ventricular fibrillation and hypotension while in
      hospital. CONCLUSION: Among hospital survivors of a confirmed or suspected acute
      coronary syndrome predictors of death during 5 years were: age, male sex, history
      of AMI, diabetes mellitus and smoking, development of AMI and congestive heart
      failure while in hospital and prescription of digitalis and diuretics at hospital
      discharge. A history of smoking and angina pectoris as well as development of
      hypotension and ventricular fibrillation while in hospital interacted
      significantly with the relationship between development of AMI and prognosis.

PMID- 9781790
TI  - Prevalence of type 2 diabetes mellitus and risk of hypertension and coronary
      artery disease in rural and urban population with low rates of obesity.
AB  - OBJECTIVE: To compare the prevalence of type 2 diabetes mellitus (DM) and
      coronary artery disease (CAD) and hypertension in DM in the rural and urban
      populations of north India. DESIGN AND METHODS: Two populations of the same
      ethnic background were randomly selected for this cross sectional survey. There
      were 1769 rural (894 men, 875 women) and 1806 urban subjects (904 men, 902 women)
      between 25-64 years of age. The survey methods included fasting and 2 h blood
      glucose and electro-cardiogram and blood pressure measurement of all subjects.
      RESULTS: Using the criteria of World Health Organization, the prevalence of
      diabetes mellitus (6.0 vs 2.8%) hypertension (24.0 vs 17.0%) and CAD (9.0 vs
      3.2%) was significantly (P<0.001) higher in urban compared to rural subjects.
      Hypertension and CAD were significantly more frequent among subjects with
      diabetes compared to nondiabetes. The association of CAD and hypertension with
      diabetes was greater in urban than rural subjects. Excess body weight and
      obesity, central obesity, sedentary lifestyle, higher visible fat intake (>25
      g/day), and social class 1-3 (higher and middle) were significantly associated
      with diabetes. Multivariate logistic regression analysis showed that after
      adjustment of age and sex, body mass index, central obesity, sedentary lifestyle
      and higher visible fat intake and alcohol intake in men were significant risk
      factors of diabetes among all the sub-groups. CONCLUSIONS: The study showed a
      high prevalence of diabetes in urban north Indian population compared to rural
      subjects in the same ethnic group. CAD and hypertension were significantly
      associated with diabetes more in urban than rural subjects. The findings suggest
      that higher body mass index, waist-hip ratio and visible fat intake and sedentary
      lifestyle were risk factors of diabetes.

PMID- 9781792
TI  - Cross-sectional and Doppler echocardiographic diagnosis of anomalous origin of
      the left coronary artery from the pulmonary artery and right coronary artery from
      posterior aortic sinus.
AB  - A six-year-old asymptomatic child on evaluation for a cardiac murmur, was found
      on cross-sectional and Doppler echocardiography to have an anomalous origin of
      the left coronary artery from the pulmonary artery and right coronary artery from
      posterior sinus of aorta. Doppler studies revealed a continuous signal in the
      pulmonary artery, indicating a left to right flow. The diagnosis was subsequently
      confirmed at cardiac catheterization and surgery.

PMID- 9781793
TI  - Unguarded tricuspid orifice and patent right ventricular outflow tract presenting
      with long-standing severe right heart failure in an adult.

PMID- 9781794
TI  - Influence of beta-blockers on the frequency of arrhythmia recurrences in patients
      with implantable cardioverter-defibrillator: an intraindividual comparison.
AB  - We studied retrospectively 60 consecutive recipients of an implantable
      cardioverter-defibrillator and identified 16 patients who were temporarily on and
      off beta-blockers (further medication unchanged). An intraindividual analysis
      revealed that 56% of the patients experienced more arrhythmic episodes during
      follow-up off beta-blockers compared to 44% while being on beta-blockers. Also,
      the mean episode frequency during follow-up time on and off beta-blockers was
      comparable (0.4+/-0.6 vs. 0.5+/-0.5, ns).

PMID- 9781795
TI  - Cardioverter-defibrillator oversensing due to double counting of ventricular
      tachycardia electrograms.
AB  - We report a case of a patient with idiopathic dilated cardiomyopathy and
      recurrent ventricular tachycardias refractory to antiarrhythmic treatment with
      amiodarone. A cardioverter defibrillator implantation was performed by the
      transvenous technique, but ventricular tachycardia detection resulted to be
      inappropriate because of constant double sensing of ventricular tachycardia
      electrograms (QRS width=250 ms). Device programmability didn't allow a
      satisfactory solution to this problem, therefore a more appropriate sensing
      system was considered. Through an anterior thoracotomy two epicardial wires were
      positioned and sensing by these wires, placed closer to ventricular tachycardia
      origin, resulted appropriate. An electrophysiologic study and subsequent follow
      up confirmed appropriate ICD detection of ventricular tachycardias. This case
      emphasizes how in some cases sensing by epicardial wires may be a solution for
      QRS double counting occurring with endocardial leads during ventricular
      tachycardia.

PMID- 9781796
TI  - Balloon mitral valvotomy in juvenile rheumatic mitral stenosis.

PMID- 9781797
TI  - Combined therapy with a beta-blocker and a calcium-channel blocker in dilated
      cardiomyopathy.

PMID- 9781798
TI  - Takayasu arteritis presented with acute febrile pericardial effusion.
AB  - We report the clinical and radiographic findings of Takayasu arteritis (TA)
      presented with acute febrile pericardial effusion. Our case is unique in that
      acute pericardial effusion developed in the absence of other intracardiac
      abnormalities as an initial manifestation of TA. While pericardial effusion is
      infrequently related with TA, TA should be considered as one of causes of acute
      febrile pericardial effusion in especially young women.

PMID- 9781799
TI  - Pulmonary hypertensive crisis as an initial manifestation of intracranial
      arteriovenous malformation with aneurysm of the vein of Galen.

PMID- 9781800
TI  - Flail tricuspid valve in a patient with history of stab chest wound.
AB  - Cardiac sequelae of stab chest wounds may be various and dramatic, and the right
      ventricle is the most commonly injured chamber. Correct diagnosis of cardiac
      damage may be done up to many years after the trauma. We describe a rare case of
      isolated, unexpected flail tricuspid valve detected by transthoracic
      echocardiography in a young patient with remote history of stab chest wound.

PMID- 9781801
TI  - Aspirin improves organic nitrate treatment for angina pectoris. Calcium channel
      antagonists do not decrease plasma inorganic nitrate levels.

PMID- 9781802
TI  - A pilot double-blind, randomized, and placebo-controlled study of orally
      administered IFN-alpha-n1 (Ins) in pediatric patients with measles.
AB  - To determine the safety and effectiveness of low-dose oral interferon-alpha (IFN
      alpha) against measles, 30 confined pediatric patients were prospectively and
      randomly assigned to either a placebo or an oral IFN-alpha group and observed
      daily for 14 days in a double-blind manner. The IFN patients received a daily
      sublingual dose of 200 IU of human lymphoblastoid IFN-alpha. The IFN-treated
      group showed shorter average duration of malaise (3.2 vs. 10.7 days, p < 0.0001),
      anorexia (3.1 vs. 6.7 days, p < 0.0001), and irritability (1.1 vs. 2.2 days, p <
      0.01) and shorter duration of macular/maculopapular/papular lesions (4.3 vs. 8.2
      days,p < 0.0001) and branny desquamation (4.6 vs. 5.8 days, p > 0.05) and shorter
      time for rash to become generalized (5.5 vs. 10.3 days, p < 0.0001). No
      hematologic, renal, or liver toxicities were noted. It, therefore, appears that
      low-dose oral human lymphoblastoid IFN-alpha used in this pilot study is both
      safe and effective in children with measles infection.

PMID- 9781803
TI  - Expression of interleukin-18 in murine contact hypersensitivity.
AB  - In this study, we made a mouse model for contact hypersensitivity (CH) using
      oxazolone as a contact allergen and examined the expression of interleukin-18 (IL
      18) in the diseased skin sites at both mRNA and protein levels. In the kinetic
      study by semiquantitative RT-PCR, IL-18 mRNA was constitutively produced in
      normal murine skin but increased significantly at 12 h and peaked at 24 h in the
      ear skin of CH mice. A positive correlation was confirmed between the IL-18 mRNA
      signal and CH, as measured by mouse ear swelling response. Histologically, in
      situ hybridization showed that the IL-18 mRNA signal was weakly observed in the
      dermis but not the epidermis of normal skin, whereas the IL-18 mRNA signal was
      found intensively in the dermis, particularly in inflammatory cell areas. Using
      IL-18-specific antibody immunostaining, it was further found that IL-18 protein
      production had a histologic location similar to that of IL-18 mRNA in both normal
      and CH mice. The present study suggests that IL-18 may be implicated in the
      pathogenesis of murine CH.

PMID- 9781804
TI  - Oral-mucosal administration of IFN-alpha potentiates immune response in mice.
AB  - We studied the effects of oral-mucosal administration of murine interferon-alpha
      (Mu-IFN-alpha) on immune responses and infection with vaccinia virus (VV) in
      mice. When Mu-IFN-alpha was administered to sheep red blood cell (SRBC)
      sensitized mice for 4 or 5 days, Mu-IFN-alpha significantly enhanced delayed-type
      hypersensitivity (DTH) and antibody production, with maximum enhancement of each
      at 1 IU/body. To investigate the antiviral effect of oral-mucosal Mu-IFN-alpha,
      mice were infected with VV, and Mu-IFN-alpha was administered for 15 days. Pocks
      were observed in the tail skin of infected mice, and Mu-IFN-alpha at doses of 1,
      10, and 100 IU/body significantly suppressed pock formation. Also, VV-specific
      cytotoxic T cells (CTL) were observed in the spleen from the same mice at 7 days
      after infection, and Mu-IFN-alpha enhanced CTL activity at doses above 1 IU/body.
      These results suggest that the oral-mucosal Mu-IFN-alpha may have potentiating
      effects on cellular and humoral immune responses, which may contribute to its
      effects against VV.

PMID- 9781806
TI  - Herpes simplex virus replication-induced expression of chemokines and
      proinflammatory cytokines in the eye: implications in herpetic stromal keratitis.
AB  - On infection of the cornea with herpes simplex virus (HSV), an immunopathologic
      response termed herpetic stromal keratitis (HSK) ensues. This response is
      mediated primarily by CD4+ T cells and only occurs if mice are infected with
      replication-competent virus, although replication-defective mutants induce
      cellular immune responses following infection. To determine the consequences of
      HSV replication in the cornea, which is crucial for HSK manifestation, corneas
      infected with productive virus and replication-defective mutants were analyzed
      for chemokines and proinflammatory cytokine mRNA expression by RT-PCR at various
      times. While productive infection resulted in rapid upregulation and sustained
      expression of such chemokines as N51/KC, macrophage inflammatory protein-1beta
      (MIP-1beta), MIP-2, and monocyte chemotactic protein-1 (MCP-1) and such cytokines
      as interleukin-1 (IL-1), IL-6, IL-12, and tumor necrosis factor-alpha (TNF
      alpha), expression of such inflammatory mediators was minimal and transient after
      unproductive infection. Expression of MIP-1alpha and lymphotactin along with a
      biphasic expression of IL-6 and MIP-2 were seen only with productive infection.
      Initial PMN recruitment into the cornea was approximately 50-fold greater with
      productive infection than with unproductive infection. These data suggest that a
      replication-induced proinflammatory milieu in the cornea is crucial for the
      subsequent progression of HSK possibly because of enhancement of the expression
      of corneal agonists that drive HSK manifestation.

PMID- 9781805
TI  - Role of cytokines in GVL (ESb lymphoma) and GVHD after adoptive transfer of
      allogeneic T lymphocytes in mice.
AB  - ESb lymphoma cells injected i.v. into DBA/2 (H-2d) mice multiply rapidly in the
      liver and kill all mice in a few days. Adoptive transfer of allogeneic C57B1/6 (H
      2b) tumor-immune or normal splenic lymphocytes to sublethally irradiated DBA/2
      mice induced a marked antitumor state, graft-versus-leukemia (GVL), increasing
      the mean survival time 2-3-fold, but also induced an acute and lethal graft
      versus host disease (GVHD). We have undertaken experiments to try to dissociate
      GVL from GVHD. Transfer of immune spleen cells induced a greater GVL than
      transfer of normal spleen cells with an equivalent to GVHD. Three to five million
      immune or normal CD8+ T lymphocytes were sufficient to induce both GVL and GVHD.
      Individual DBA/2 mice were labeled and followed. In mice undergoing GVHD, the
      spleens were repopulated by donor (H-2b) lymphocytes, and tumor necrosis factor
      alpha (TNF-alpha) and interleukin-6 (IL-6) were present in the sera of 26 of 27
      and 18 of 20 mice, respectively, together with increased amounts of TNF-alpha and
      IL-6 mRNA in their spleens. This was in contrast to DBA/2 mice receiving
      allogeneic cells but not developing GVHD. Both interferon-alpha/beta (IFN
      alpha/beta) and IL-12, which had proven very effective in association with
      adoptive transfer of syngeneic immune T lymphocytes in inhibiting ESb metastases,
      enhanced GVHD when administered with allogeneic immune or normal spleen cells,
      and >90% of mice died. Intensive IL-2 treatment inhibited GVHD while maintaining
      GVL.

PMID- 9781807
TI  - In vivo induction of the interferon-stimulated protein 2'5'-oligoadenylate
      synthetase in tumor and peripheral blood cells during IFN-alpha treatment of
      metastatic melanoma.
AB  - Interferon-alpha (IFN-alpha) therapy induces a response in a proportion of
      patients with metastatic melanoma. However, the mechanism of the antitumor action
      and reason(s) for resistance to IFN therapy are not known. To investigate whether
      lack of clinical response may be due to resistance of the melanoma cells to IFN
      alpha or to an inability of IFN-alpha to reach the tumor cells during treatment,
      we investigated the in vivo and in vitro susceptibility of primary tumor cells
      obtained through fine needle aspiration biopsies and peripheral blood mononuclear
      cells (PBMC) to the induction of the IFN-induced enzyme 2'5'-oligoadenylate
      synthetase (2'5'OAS) during initiation of IFN-alpha therapy in 10 patients with
      metastatic melanoma. None of the patients showed an objective response to IFN
      alpha treatment. The melanoma cells from 2 of the 10 patients were resistant to
      IFN-induced enhancement of 2'5'OAS in vitro. This correlated well with the in
      vivo induction of 2'5'OAS in the malignant cells, as no in vivo induction was
      seen in the 2 patients whose malignant cells were resistant in vitro, whereas
      tumor cells from 7 of 8 of the remaining patients showed enhancement also in
      vivo. This study shows that it is possible to monitor the cellular susceptibility
      of tumor cells to IFN-alpha in vivo and that melanoma cells from a small
      percentage of patients are resistant to the cellular effects of IFN-alpha.
      Furthermore, the absence of a clinical response to IFN-alpha therapy in the
      majority of melanoma patients can be explained neither by impaired cellular
      susceptibility to IFN nor by an inability of IFN-alpha to reach the tumor.

PMID- 9781808
TI  - Differential induction of IL-12 by IFN-beta and IFN-gamma in human macrophages.
AB  - Interleukin-12 (IL-12) is a proinflammatory cytokine secreted by antigen
      presenting cells (APC) in response to microbial antigens and mitogens. IL-12
      induces interferon-gamma (IFN-gamma) production and enhances cellular immune
      responses. Conversely, IFN-gamma does not induce IL-12 but can prime its
      production by phagocytic cells in response to antigenic stimuli. In this study,
      we examined the effect of IFN-beta on IL-12 production in human macrophages, as
      IFN-beta is a natural protein produced by virus-infected cells. We demonstrate
      that, unlike IFN-gamma, IFN-beta is able to induce IL-12 production in
      macrophages. However, IFN-gamma can enhance IFN-beta-induced IL-12 in these
      cells. These findings suggest that IFN-beta could influence the immune response
      to virus infection indirectly through IL-12.

PMID- 9781809
TI  - Relationship among hepatic inflammatory changes, circulating levels of cytokines,
      and response to IFN-alpha in chronic hepatitis C.
AB  - To investigate the relationship among circulating cytokines, inflammation in the
      liver, and kind of response to interferon-alpha (IFN-alpha) in hepatitis C, we
      studied 63 consecutive patients (38 male, 25 female), treated with IFN for up to
      1 year. Serum tumor necrosis factor-alpha (TNF-alpha) was measured at baseline
      and after 3 months of treatment. Transient (TR) or sustained response (SR) was
      observed in 29 and 16 patients, respectively. Baseline levels of TNF < or = 22
      ng/L were observed in 69% of patients with SR, 55% of patients with TR, and 22%
      of nonresponders (p < 0.01). There was a significant correlation between baseline
      TNF levels and histologic grading score of hepatitis (p < 0.01). After 3 months
      of treatment, TNF levels >22 ng/L were observed in 63% of patients with SR, 69%
      of patients with TR, and 83% of nonresponders (p NS). Independent of the
      treatment outcome, TNF levels were lower at baseline and increased significantly
      with treatment in patients with lower histologic grading (p < 0.005). In
      conclusion, in patients with chronic hepatitis C, circulating TNF levels
      correlate with the degree of inflammation in the liver. Response to IFN is
      accompanied by an inflammatory response involving the release of TNF.

PMID- 9781810
TI  - Avian IFN-gamma genes: sequence analysis suggests probable cross-species
      reactivity among galliforms.
AB  - Little is known about the evolution of cytokines in non-mammalian systems. To
      address this problem, we attempted to clone the gene for interferon-gamma (IFN
      gamma) from a variety of avian species using oligonucleotide primers based on the
      sequence of the chicken IFN-gamma gene. The coding sequence and partial intron
      sequences were determined for four species, namely guinea fowl, ring-necked
      pheasant, Japanese quail, and turkey. To obtain sequence information on the gene
      extremities, a modified 5' and 3' RACE protocol was used. The sequence
      information showed that the coding regions of the IFN-gamma gene are highly
      conserved among the species studied (93.5%-96.7% and 87.8%-97.6% at the
      nucleotide and peptide levels, respectively) and are more conserved at the amino
      terminal region (exons 1 and 2) than the carboxyl-terminal (exons 3 and 4). This
      high degree of overall identity at the predicted primary amino acid sequence
      level of the protein, including the deduced IFN-gamma receptor binding motifs,
      suggests that IFN-gamma may be cross-reactive among these species. Phylogenetic
      analysis shows that the similarity of the avian IFN-gamma sequences parallels the
      presumed evolutionary relationships between the species.

PMID- 9781811
TI  - Role of the vaccinia virus E3L and K3L gene products in rescue of VSV and EMCV
      from the effects of IFN-alpha.
AB  - Vaccinia virus (VV) has been shown to be relatively resistant to the antiviral
      effects of interferon-alpha (IFN-alpha) and to rescue replication of IFN
      sensitive viruses, such as encephalomyocarditis virus (EMCV) and vesicular
      stomatitis virus (VSV), from the antiviral effects of IFN. The E3L and K3L gene
      products have been implicated in the IFN resistance of VV. We have investigated
      the role that these VV-encoded functions play in the rescue of VSV and EMCV from
      the effects of IFN. Transient expression of the E3L open reading frame (ORF) was
      sufficient to rescue VSV but not EMCV from the IFN-induced antiviral state.
      Rescue of VSV by mutants of E3L correlated with the ability of the mutated E3L
      gene products to bind dsRNA. Conversely, transient expression of the K3L ORF was
      sufficient to partially rescue EMCV but not VSV from the effects of IFN. Results
      with VV deleted of either the K3L or E3L ORFs were consistent with results
      obtained by transient expression of these genes. These results demonstrate that
      the VV E3L gene products are likely responsible for the VV-mediated rescue of VSV
      from the effects of IFN and the K3L gene product is likely at least partly
      responsible for rescue of EMCV.

PMID- 9781812
TI  - Trophoblast IFN-tau differentially induces lymphopenia and neutropenia in lambs.
AB  - Type I interferons (IFN), including IFN-alpha and IFN-beta, cause severe
      lymphopenia, resulting from altered lymphocyte recirculation and redistribution.
      IFN-tau, a product of trophectoderm of ruminant conceptuses and new member of the
      type I IFN family has not been examined for its effect on leukocyte
      recirculation. Additionally, differential effects of type I IFNs on the
      redistribution and recirculation of subsets of T cells have not been reported.
      The present study determined the effects of IFN-tau on the redistribution and
      recirculation of ovine leukocytes and T cell subsets. Total peripheral blood
      leukocytes, lymphocytes, and segmented neutrophils were reduced (p < 0.05)
      following treatment of lambs with IFN-tau. Furthermore, administration of IFN-tau
      caused an acute, differential reduction in peripheral blood CD4+ T cells (p <
      0.05), CD5+ cells (p < 0.05), and gammadelta TCR+ (p < 0.01) T cells but had no
      effect on CD8+ T cells (p > 0.05). IFN-tau reduced the percentage of gammadelta T
      cells by 8-fold and that of CD4+ T cells and CD5+ cells by <2-fold in peripheral
      blood when compared with control lambs. The reduction in leukocytes, lymphocytes,
      and neutrophils was observed as early as 6-12 h after administration of IFN-tau,
      but levels returned to control values within 48 h. These results indicate that
      IFN-tau, like other members of the type I IFN family, can have immediate effects
      on leukocyte recirculation and redistribution. The present study is the first to
      demonstrate that IFN-tau differentially regulates T cell recirculation with the
      greatest effect on gammadelta TcR+ T cells.

PMID- 9781813
TI  - Recombinant porcine IFN-gamma potentiates the secondary IgG and IgA responses to
      an inactivated suid herpesvirus-1 vaccine and reduces postchallenge weight loss
      and fever in pigs.
AB  - The effect of recombinant porcine interferon-gamma (IFN-gamma) on the
      immunogenicity in vivo of inactivated suid herpesvirus-1 (SHV-1, Phylaxia strain)
      was studied applying two successive i.m. immunizations. The animals were injected
      with inactivated virus alone or inactivated virus supplemented with 10(4) or
      10(6) U IFN-gamma. After the first immunization, none of the animals responded
      with measurable virus-neutralizing antibody (VNAb), virus-specific IgG or IgA.
      Following a second immunization 4 weeks later, a significantly increased VNAb
      response was noted in animals that had received vaccine doses containing 10(4) U
      IFN-gamma (p < 0.05). These animals also had significantly augmented serum levels
      of IgG (p < 0.01) and IgA (p < 0.05). Inclusion of 10(6) U IFN-gamma in the
      vaccine preparation did not affect the antibody response. In one experiment, the
      pigs were challenged oronasally with 10(5) TCID50 of the 75V19 strain of SHV-1, 7
      weeks after administration of the second vaccine dose. Those that had received
      10(4) U IFN-gamma in the vaccination developed less fever during the
      postchallenge period (p < 0.004). In all challenged pigs, growth performance was
      compromised during the first week after challenge. However, the only animals
      retaining an average net increase in body mass were those covaccinated with 10(4)
      U IFN-gamma (p < 0.05). Nasal excretion of virus was not significantly different
      between groups that had been vaccinated with or without IFN-gamma. Multiple
      linear regression analysis of variables from individual vaccinated animals
      revealed the VNAb response to be correlated with serum IgG levels (p < 0.025) and
      with postchallenge growth performance (p < 0.0001) but not with serum IgA levels
      (p > 0.5). On the other hand, serum IgA appeared to be inversely correlated with
      early nasal virus excretion after challenge (p < 0.006). Taken together, our data
      suggest that addition of IFN-gamma to inactivated SHV-1 vaccine may be a useful
      tool for enhancement of both mucosal and systemic immune responses in pigs.

PMID- 9781814
TI  - Cloning and characterization of cDNAs for a bovine (Bos taurus) Mx protein.
AB  - Mx proteins are GTPases that are stringently induced in cells from many
      vertebrates on exposure to type I interferons (IFNs), and expression of some Mx
      proteins potently inhibits replication of specific viruses. Two cDNAs encoding
      bovine Mx proteins were isolated from an endometrial phage library. The open
      reading frames (ORFs) of these two clones predict proteins of 654 (Mxl) and 648
      (Mxl-a) residues. Both possess the tripartite GTPase domains, dynamin signature,
      and leucine zipper motifs conserved in all other Mx proteins identified. The
      bovine protein sequences show highest identity to ovine Mx (93%) and are
      substantially similar to human MxA (73%) and mouse Mx1 (63%). Based on
      differences between the two bovine clones in the coding and 3'-untranslated
      regions, it was concluded that they represent two alleles of one gene, and
      heterozygous and homozygous cattle were identified. Expression of Mx mRNA was
      rapidly induced in cultured bovine cells by treatment with IFN.

PMID- 9781815
TI  - Biochemical and genetic evidence for complex formation between the influenza A
      virus NS1 protein and the interferon-induced PKR protein kinase.
AB  - The interferon (IFN)-induced protein kinase (PKR) functions as a gatekeeper of
      mRNA translation initiation and is, therefore, a key mediator of the host IFN
      induced antiviral defense system. Many viruses have invested countermeasures
      against PKR. Some apparently use more than one mechanism. The influenza virus can
      repress PKR activity through the use of at least two factors, the cellular P58IPK
      protein and the viral NS1 protein. The exact mode of action of the latter has not
      been established. Here, using a coprecipitation assay, we found that PKR could
      form a complex with NS1 in crude cell extracts prepared from influenza virus
      infected HeLa cells. The NS1-PKR interaction was verified by using the yeast two
      hybrid system and an in vitro binding assay. Deletion analysis mapped the NS1
      binding site to the N-terminal 98 residues of PKR regulatory region. Furthermore,
      an NS1 mutant, which lacks PKR inhibitory activity, did not bind PKR. Finally,
      the functional role of NS1 in PKR inhibition was substantiated using an in vivo
      assay for PKR activity. These results support the role of NS1 in PKR modulation
      during viral infection that is mediated through a complex formation between the
      two proteins.

PMID- 9781816
TI  - Interferon-induced upregulation and cytoplasmic localization of Myc-interacting
      protein Nmi.
AB  - Nmi interacts with c-Myc, N-Myc, Max, and fos, as demonstrated by yeast two
      hybrid and coimmunoprecipitation assays. Nmi is partially homologous to IFP 35,
      an interferon (IFN)-inducible protein. In this study, we show that basal
      expression of Nmi is upregulated by IFN in multiple tumor-derived cell lines.
      Treatment with IFN results in an increased amount of cytoplasmic Nmi distributed
      in a punctate granular pattern. We also demonstrate that Nmi is expressed in
      various fetal and adult tissues. As Nmi does not contain a known DNA-binding
      motif, it has the potential to form inactive heterodimers with its putative DNA
      binding partners. Our studies suggest that Nmi may modulate its binding partners
      in an IFN-inducible manner.

PMID- 9781817
TI  - The proximal interferon-stimulated response elements are essential for interferon
      responsiveness: a promoter analysis of the antiviral MxA gene.
AB  - Interferon (IFN)-inducible human MxA protein mediates resistance against
      influenza and several other RNA viruses. The MxA gene is under the control of
      type I IFN and, in certain cell types, is also directly activated by viruses.
      Here we show that in human macrophages, MxA mRNA levels are upregulated by very
      low doses of IFN-alpha in a dose-dependent manner. A similar, albeit much weaker,
      dose-dependent induction was seen with IFN-gamma. The induction was rapid and
      independent of protein synthesis. Interleukin-6 (IL-6) or tumor necrosis factor
      alpha (TNF-alpha) did not influence MxA mRNA levels alone or in combination with
      IFNs, in spite of the presence of putative response elements of these cytokines
      in the MxA promoter. We show that the promoter of the MxA gene contains two
      functional IFN-stimulated response elements (ISRE) near the transcription start
      site and one homologous ISRE-like element, which is apparently nonfunctional,
      further upstream. The two proximal ISRE sites are essential for IFN-alpha-induced
      transcription and appear to be binding sites for IFN-stimulated gene factor 3
      complex. In addition, EMSA and DNAse I footprinting analysis demonstrated that
      Spl binds with high affinity to a region encompassing nucleotides -25 and -50
      and, thus, may provide means of interaction with the basal transcriptional
      machinery.

PMID- 9781818
TI  - Specific targeting of cytokine-secreting cells: a bispecific diabody recognizing
      human interleukin-6 and CD3 induces T cell-mediated killing.
AB  - Cytokines have been implicated in the pathophysiology of many diseases. Although
      there have been many attempts to neutralize the activity of cytokines in vivo and
      in vitro, no strategies have been developed to specifically eliminate cells that
      overexpress cytokines. Considering the fact that cytokines in part remain cell
      associated on secretion, we have constructed a bispecific diabody consisting of a
      nonneutralizing scFv antibody recognizing human interleukin-6 (IL-6) and an scFv
      corresponding to the monoclonal antibody (mAb) OKT3, which recognizes and
      activates the human T cell receptor. Here we show that the diabody recognized
      both human IL-6 and human CD3. In the presence of human T cells, the diabody
      induced killing of human hepatoma cells that had been transfected with a human IL
      6 cDNA. The extent of killing was dependent on the ratio of effector/target cells
      and increased with increasing concentrations of the diabody. Untransfected
      control cells or human hepatoma cells that secrete the IL-6-related cytokine
      leukemia inhibitory factor (LIF) remained unaffected. We conclude that diabodies
      recognizing cytokines can be used to specifically target cytokine-secreting
      cells.

PMID- 9781819
TI  - Sleep-associated changes in interleukin-1beta mRNA in the brain.
AB  - Much evidence implicates interleukin-1beta (IL-1beta) in sleep regulation. Two
      previous studies indicated that levels of IL-1beta in mRNA were affected by
      sleep. In the current study, levels of IL-1beta mRNA and IL-1 receptor assessory
      protein (IL-1RAP) mRNA were determined 1 h after the beginning of light and dark
      periods and after sleep deprivation, using the reverse transcriptase-polymerase
      chain reaction (RT-PCR) and mutated internal standards. Daytime samples contained
      relatively more IL-1beta mRNA than nighttime samples, and levels of IL-1beta mRNA
      were higher after sleep deprivation. These changes occurred in the hypothalamus,
      hippocampus, cerebral cortex, and mesencephalon/pons. In contrast, the IL-1 RAP
      mRNA level did not seem to be affected by sleep.

PMID- 9781820
TI  - Collaborative bioinformatics: data warehouses for targeted experimental results.
AB  - Current functional bioinformatics approaches are handicapped by the inability to
      store functional data at all or by a scattering of data across heterogeneous
      databases that are difficult to link and query. The Cellular Response Database
      (CRD) (http://LHI5.umbc.edu/crd) is designed to store and retrieve data
      concerning changes in in vitro cellular functions associated with stimuli, such
      as cytokines and drugs. The database can store a broad range of data, including
      protein or mRNA expression, as well as functional cellular data, such as
      apoptosis or adherence. This unique ability to store heterogeneous data using a
      single data model will minimize difficulties associated with searching multiple
      databases. Authors with articles accepted by participating journals are invited
      to submit data to the CRD. Submission instructions are outlined, along with a
      review of the CRD's development.

PMID- 9781821
TI  - Self-efficacy, outcome expectations, and fantasies as predictors of alcoholics'
      postreatment drinking.
AB  - The usefulness of distinguishing between alcoholic patients' expectations and
      their fantasies about treatment outcome was examined. Results at 6 and 12 months
      follow-up did not support the results of research with nonalcoholic participants
      which related better outcomes to a combination of positive expectations and
      negative fantasies about future drink-related situations. Higher self-efficacy
      expectancy at intake, however, was associated with better clinical outcome.
      Findings supported Bandura's (1986) contention that outcome expectations add
      little information on prediction beyond that explained by self-efficacy
      expectancy. The clinical implications of these results are discussed.

PMID- 9781822
TI  - HIV risk behaviors associated with the injection process: multiperson use of drug
      injection equipment and paraphernalia in injection drug user networks.
AB  - This study examines drug acquisition and multiperson use of paraphernalia, drugs,
      and needles/syringes. Ethnographers observed 54 injection episodes in which IDUs
      were linked by HIV risk behaviors, and developed a typology of higher-risk, lower
      risk, and nonsharing-risk networks. Multiperson use of injection paraphernalia or
      drug solution occurred in most injection events (94%). Serial use of
      syringes/needles occurred infrequently (14%) relative to "backloading" (37%) and
      reuse of paraphernalia (cookers 84%, cotton 77%, water 77%). Higher-risk
      injection networks were characterized by larger size and pooling of resources for
      drugs. Prevention messages must include avoiding reuse of injection paraphernalia
      and transfer of drug solution.

PMID- 9781823
TI  - Working in addictions treatment services: some views of a sample of service
      providers in Ontario.
AB  - Respondents in a survey of specialized addiction treatment providers indicated a
      strong commitment to the addictions field. In a multivariate analysis, intention
      to stay in the addictions field was positively related to a measure of attitudes
      toward staying or leaving, to age, involvement in an addictions studies program,
      working in a residential service, and job satisfaction. Intention to stay was
      negatively related to education and working in a nonresidential setting.
      Attention to factors that create positive attitudes to the addictions field,
      especially among younger, more educated people and those working in
      nonresidential services, is necessary to ensure a healthy future for addictions
      treatment.

PMID- 9781824
TI  - Temporal patterns of heroin and cocaine use among methadone patients.
AB  - A sample of 1,038 patients newly admitted to 15 methadone clinics in New York
      City were studied for up to three years in treatment or until discharge. Cluster
      analysis identified distinct patient groups with very different heroin and
      cocaine usage patterns during treatment. About 80% either started in or
      transitioned to a low heroin use group and 50% either started in or transitioned
      to a low cocaine use group during treatment. One-third of patients used cocaine
      extensively during treatment. Other "high risk" groups, such as those not
      recently employed, younger, or involved with criminal justice, could benefit from
      special interventions very early in treatment.

PMID- 9781825
TI  - Drug identity change processes, race, and gender. II. Microlevel motivational
      concepts.
AB  - Events and experiences that are damaging and which sever young people from
      normative ideals and positively sanctioned statuses (marginalization) create
      feelings of alienation or social isolation within them and earn them undesired
      statuses and treatment from important others. An underlying premise of the drug
      use identity change model is that individuals are motivated toward drug-related
      identity change because of such socially defined problems with existing ego
      identities (ego identity discomfort and lost control in defining an identity) in
      childhood and early adolescence and that certain macrolevel phenomena (e.g.,
      social appraisal sources and social climate conducive to drug use) provide an
      opportunity structure for that change. Part 2 of this paper describes each of the
      three motivational concepts and how they vary by race and gender in the process
      of becoming a drug misuser. Part 3 discusses the two macrolevel opportunity
      concepts and how they vary by race and gender.

PMID- 9781826
TI  - The legal importation of prescription drugs into the United States from Mexico: a
      study of Customs declaration forms.
AB  - The nature and magnitude of the problem of the diversion of prescription drugs
      from legal to illegal markets have been identified as a high priority by the
      federal government. This study was based on a random sample (2,005) of
      declaration forms of persons declaring Mexican prescription drugs at the US
      Customs office in Laredo, Texas. Of the 75 different types of drugs, the most
      frequently declared drugs were Valium (71%), Rohypnol (46%), and Tafil (25%),
      drugs highly associated with nonmedicinal use among United States teenagers and
      young adults. These data reinforce a documented need for more transnational
      cooperative efforts between the United States and Mexico.

PMID- 9781827
TI  - Using social indicators to predict addiction.
AB  - Because of cost and other constraints, states often find it difficult to estimate
      need for treatment of alcohol-related problems from routine surveys. The social
      undesirability of illegal drug use makes the assessment of need for treatment of
      their use even more difficult. This paper uses independently obtained treatment
      need estimates to provide parameters for short-term prediction. We obtained the
      parameters by regressing the proportions of people addicted to alcohol (or drugs)
      in counties on social-indicator-based relative treatment need estimates for
      alcohol (or drugs). In addition to integrating estimates coming from independent
      sources, our approach presents an important tool for planning and resource
      allocation.

PMID- 9781828
TI  - Drug use--chronic and relapsing or a treatable condition?
AB  - It is argued that the term "chronic relapsing disorder," which is used frequently
      to characterize drug use, does not capture the complexity of drug treatment
      evaluation findings and thereby limits an understanding and appreciation of the
      accomplishments of drug treatment. Specifically, it is noteworthy that a
      substantial minority (19%) of treated drug users have been found to maintain
      abstinence over a 6-year period posttreatment, and that the three major multisite
      treatment evaluations sponsored by NIDA have all found that overwhelming
      majorities of treated drug users do not revert to the levels of drug use (or
      criminal activity) shown pretreatment. Thus, the view of inevitable and
      continuing adoption of pretreatment behaviors, i.e., chronic relapse, gives
      undeserved comfort to those who deny the utility of drug treatment, and does so
      at a time when changes in the health care industry threaten the integrity of that
      treatment.

PMID- 9781829
TI  - A 12-year study (1975-1986) of mortality in methadone-maintenance patients:
      selected demographic characteristics and drug-use patterns of AIDS and non-AIDS
      related deaths.
AB  - This paper describes changes in demographic characteristics and drug use patterns
      of persons who died while enrolled in a New York City methadone-maintenance
      program during the years preceding and subsequent to the AIDS epidemic. Persons
      dying from AIDS were more likely to be younger, Hispanic, and male than those
      dying from other causes. Drug use increased during the 12-year study period, and
      the spread of the HIV infection among drug users may be reflected in an increased
      use of injectable drugs.

PMID- 9781830
TI  - Secondary stroke prevention with low-dose aspirin, sustained release dipyridamole
      alone and in combination. ESPS Investigators. European Stroke Prevention Study.
AB  - Patients who had survived a stroke or transient ischaemic attacks (TIA) were
      admitted to a trial of low-dose aspirin (50 mg) alone, sustained release
      dipyridamole (400 mg/day) alone, or a combination of the two agents, and results
      compared with a placebo over 24 months. This low-dose aspirin regimen produced in
      pairwise comparisons a significant risk reduction of 18% for stroke, 13% for
      stroke and/or death but no reduction in all cause mortality. The sustained
      release dipyridamole produced a significant risk reduction of 16% for stroke, 15%
      for stroke and/or death but no significant reduction of mortality. In
      combination, aspirin and dipyridamole produced a risk reduction of 37% in stroke,
      24% in stroke and/or death, and no reduction in mortality. Similar findings were
      found in TIA, which was a secondary endpoint. These results are highly
      significant in comparison with placebo. As expected, there were enhanced reports
      of alimentary side-effects in the aspirin groups and also enhanced bleeding.
      Dipyridamole was associated with a slight increase in headache, which resolved in
      most patients if therapy was continued. The conclusions are that 50 mg/day of
      aspirin alone or 400 mg/day of sustained release dipyridamole alone are equally
      effective in stroke and TIA prevention. When used in combination the effects were
      additive and were significantly more effective than the single agents.

PMID- 9781831
TI  - Prevention of myocardial infarction and stroke by aspirin: different mechanisms?
      Different dosage?
AB  - More than 50 randomized trials have documented the efficacy and safety of aspirin
      as an antiplatelet agent and a cardiovascular drug. However, the optimal dose for
      preventing coronary and cerebral thrombosis has long been a cause of debate. For
      patients with ischaemic heart disease the range recommended for the prevention of
      a secondary event, based on strong clinical evidence, is 75-160 mg aspirin/day.
      For patients with cerebrovascular disease, recommendations range from 30-1300
      mg/day. If these patients require a higher dose of aspirin it suggests that a
      different mechanism of action is involved. This paper considers hypotheses and
      reports the findings of recent clinical trials. The SALT study compared aspirin
      with placebo in 1360 patients with TIA or minor ischaemic stroke. It showed an
      18% reduction in the risk of stroke or death in patients receiving 75 mg
      aspirin/day. Five other trials of 55,000 patients with ischaemic cerebrovascular
      disease compared the protective effect of aspirin (range 30-300 mg/day) with
      placebo, clopidogrel, or oral anticoagulants. Aspirin was better than placebo,
      safer than oral anticoagulants, and no different from clopidogrel. The
      implications of these findings are discussed. Mechanistic studies and randomized
      clinical trials strongly suggest that the mechanism of action and dose
      requirement of the antithrombotic effect of aspirin in patients with
      cerebrovascular disease is the same as that for ischaemic heart disease.

PMID- 9781832
TI  - The results of CAPRIE, IST and CAST. Clopidogrel vs. Aspirin in Patients at Risk
      of Ischaemic Events. International Stroke Trial. Chinese Acute Stroke Trial.
AB  - The role of aspirin in the secondary prevention of ischaemic events is being
      challenged. CAPRIE, a blinded multicenter randomized trial of over 19,000
      patients followed for 1-3 years, assessed the effect of clopidogrel in the
      secondary prevention of major vascular events. Patients with a recent myocardial
      infarction, stroke or peripheral arterial disease were randomized to treatment
      with clopidogrel or aspirin. Clopidogrel was associated with a statistically
      significant, overall 8.7%, relative reduction in the risk of ischaemic events,
      but the direction and size of the effect was not homogeneous with respect to
      three predefined clinical subgroups. Clopidogrel may be slightly better in
      preventing major ischaemic events in high-risk patients, but the results of
      CAPRIE suggest that there is room for doubt. It remains to be seen whether
      treatment with clopidogrel is cost-effective compared with aspirin. However,
      aspirin may still be of value in the early treatment of acute stroke. IST was a
      20,000 patient, randomized, open-label study of aspirin plus heparin or neither
      in patients with acute ischaemic stroke that should be treated in 48 hours. There
      was a small but statistically nonsignificant reduction in mortality and
      disability at 6 months for patients allocated to early treatment with aspirin
      compared with those who were scheduled to avoid aspirin in the first 2 weeks
      after the stroke. Similar results were seen in CAST, a double-blind trial of
      aspirin vs. placebo in patients with suspected ischaemic stroke treated within 48
      hours. A meta-analysis of the results of IST, CAST and MAST-I showed a
      statistically significant effect of early aspirin treatment. The role of aspirin
      in the treatment of acute stroke within 48 hours appears to be established.

PMID- 9781833
TI  - Rationale for the combination of anti-aggregating drugs.
AB  - Different pathways of platelet activation lead to the exposure of the
      glycoprotein (GP) IIb/IIIa receptor resulting in binding with fibrinogen and
      platelet aggregation. The impact of these pathways depends on the types of
      agonist present. Most agonists release arachidonic acid (AA), which is
      metabolised to thromboxane A2 (TXA2). This increases intracellular calcium, which
      is crucial for exposure of the GP IIb/IIIa receptor and the release of the dense
      and/or alpha granule contents. Anti-aggregating drugs act via different
      mechanisms. Some antagonise pro-aggregating stimuli while others inhibit the
      metabolism of AA to TXA2, blocking only one pathway of aggregation and not
      affecting granule content release. Agents that increase cAMP and/or cGMP
      interfere with all known pathways of aggregation and with the release mechanism.
      Inhibitors of cAMP and/or cGMP specific phosphodiesterases also increase
      intracellular nucleotide concentrations and a stimulatory agent together with a
      phosphodiesterase inhibitor is a very effective combination. Finally, GP IIb/IIIa
      antagonists abolish the binding of fibrinogen to the platelets, which inhibits
      platelet aggregation but leaves the release reaction intact. Different mediators
      cause aggregation via different pathways. Thus a broader spectrum of anti
      aggregating activity can be expected by combining drugs accordingly. Drug
      combination might also increase the chances of interfering more efficiently with
      the release reaction, thereby preventing the release of pro-coagulant and growth
      factors. Synergism might also lead to a reduction in dosage and a decreased risk
      of side-effects.

PMID- 9781834
TI  - Involvement of adenosine in vanadate-stimulated release of lipoprotein lipase
      activity.
AB  - A short-term incubation of isolated rat fat pads with vanadate showed the
      stimulated release of lipoprotein lipase (LPL) activity and suppression of the
      rise in extracellular adenosine level. The addition of adenosine to the medium
      showed inhibition of both the stimulated release of LPL activity and an increase
      in intracellular cAMP content by vanadate. A progressive increase in 5'
      nucleotidase activity in the particulate fraction containing plasma membrane was
      suppressed by vanadate in a time- and dose-dependent manner, suggesting that
      vanadate inhibits, in part, the production of adenosine based on a
      dephosphorylation of AMP. In adipocytes, the inhibition of adenylate cyclase via
      A1 adenosine receptor is more predominant than the stimulation of adenylate
      cyclase via A2 adenosine receptor (Londos C. et al., Proc. Natl. Acad. Sci.
      U.S.A., 75, 5362-5366 (1978)). Therefore, vanadate may stimulate the release of
      LPL activity from the fat pads by suppressing the rise in extracellular adenosine
      level, accompanied by the activation of adenylate cyclase activity.

PMID- 9781835
TI  - Identification of active substances from Streptomyces culture fluids using p53
      independent expression of p21/WAF1/Cip1 gene and their mode of action.
AB  - An assay system was constructed to identify chemicals that have a potential to
      induce p21/WAF1 gene, a target of the tumor suppressor p53 critical for negative
      growth regulation. Screening of about 1300 culture fluids of Streptomyces
      resulted in identification of active substances which induced the p21 gene in a
      p53-independent manner; one was a mixture of four members of the actinomycin
      group, and the other was trichostatin A. Transcriptional regulatory regions of
      p21 gene for induction by actinomycin D and trichostatin A were determined by
      transient expression of luciferase constructs in cells which are p53-deficient
      (Saos-2) or express a mutated form of p53 (TMK-1). The essential transcriptional
      elements for the response to these drugs localize within 210 bp of the 5'
      upstream region of human p21 gene, and Sp1 elements were determined to be
      critical for the induction. DNA-binding activity of Sp1 was not increased in
      cells treated with these drugs, but kinase inhibitors such as staurosporin and
      wortmannin inhibited the induction.

PMID- 9781836
TI  - Characteristic expression of 105-kDa heat shock protein (HSP105) in various
      tissues of nonstressed and heat-stressed rats.
AB  - Although the induction of heat shock proteins (HSP) has been studied extensively
      in cultured cells, comparatively few studies have examined their expression in
      vivo. In this report, we investigated the expression and the state of 105-kDa
      heat shock protein (HSP105) in various tissues of rats, and found that two
      isoforms of HSP105 (HSP105-a and HSP105-b) were both moderately expressed in
      adrenal, spleen, liver and heart, and both increased markedly after heat shock.
      However, in brain HSP105-a was characteristically highly expressed over HSP105-b,
      but neither increased after heat shock. In addition, a 100-kDa protein (p100), a
      possible testis-specific HSP105 homologue was found in testis. When the effects
      of adrenaline and its antagonists on the heat-inducibility of HSP105 were
      examined, the induction of HSP105 in adrenal gland seemed to be negatively
      regulated through the alpha-adrenergic receptor. Furthermore, HSP105 was found to
      be associated with HSC70/HSP70, and to exist as high molecular mass complexes of
      300-800-kDa and of 300-500-kDa in various tissues of nonstressed and heat
      stressed rats, respectively. The molecular interaction between HSP105 and HSC70
      suggests the possibility that HSP105 functions with HSC70 cooperatively in
      various tissues of rats.

PMID- 9781837
TI  - Increase in telomere sequence-binding activity in normal human fibroblasts in
      senescence or in cells treated with phorbol ester or N-methyl-N'-nitro-N
      nitrosoguanidine.
AB  - The telomere is a specialized chromatin structure composed of unique repetitive
      DNA sequences and specific nuclear proteins. Telomere sequence-binding activity
      was measured by a mobility shift assay using nuclear extract from normal human
      fibroblasts. The specific binding activity to the telomere sequence increased in
      cells that were in a senescence state compared to that in cells at early
      population doublings. Treatment of cells with tumor promoting phorbol ester TPA
      induced an increase in the telomere sequence binding activity of nuclear extract
      in young cells, but the increase was marginal in senescent cells. DNA-damaging N
      methyl-N'-nitro-N-nitrosoguanidine (MNNG) also increased the telomere sequence
      binding activity in young cells, but not in senescent cells. As a reference, we
      measured the binding activity to NFkB sequence. It was activated by TPA or
      okadaic acid, but was not affected by MNNG or in senescence. The increase in
      telomere sequence-binding activity seemed to depend on activation of tyrosine
      phosphorylation, since an inhibitor of Tyr-kinase abolished the increase in
      telomere-binding activity. The molecular weight of the major binding factor in
      the normal human fibroblasts was approximately 32 kDa which is different from
      that of the telomere-associated protein, TRF-1.

PMID- 9781838
TI  - Preventive effects of Shichimotsu-koka-to on renal lesions in stroke-prone
      spontaneously hypertensive rats.
AB  - Shichimotsu-koka-to (SKT) has been prescribed to treat patients with essential
      and renal hypertension. We investigated the effects of SKT on renal lesions in
      stroke-prone spontaneously hypertensive rats (SHRSPs). SHRSPs were given an
      extract of SKT by mixing it with drinking water, from 8 through 29 weeks of age,
      so that the average intake of SKT extract was about 1.5 g/kg/d. At 29 weeks of
      age, the kidneys of SHRSPs exhibited proliferative arteritis characterized by the
      proliferation of smooth muscle cells in the interlobular arteries, dilation and
      degeneration of renal tubules, infiltration of inflammatory cells and hemorrhage,
      with partial swelling or necrotizing of glomeruli. In particular, arteritis and
      periarteritis were noted. The treatment of SHRSPs with SKT ameliorated this
      morphological damage in the kidney and significantly decreased urea nitrogen in
      the serum. Treatment with SKT also strongly decreased the xanthine oxidase (XOD)
      activity and significantly increased the superoxide dismutase (SOD) activity in
      the kidney of SHRSPs; consequently, these values became close to those in
      normotensive Wistar Kyoto rats (WKYs). These results indicate that treatment with
      SKT ameliorated the histopathological damage and change in activity of enzymes
      related to free radicals in the kidney of SHRSPs, which may be important
      mechanisms for SKT for protecting SHRSPs from renal dysfunction.

PMID- 9781839
TI  - Pharmacological properties of T-3762, a novel fluoroquinolone antimicrobial agent
      in parenteral use. III. Chemical structures and dermovascular permeability
      increasing activities.
AB  - Fluoroquinolone antibiotics and chemically related compounds including the
      pazufloxacin methanesulfonate named T-3762 were examined for their ability to
      increase cutaneous vascular permeability following intradermal injection in dogs.
      A positive skin reaction was produced by the injection of a compound with a
      substituent of the piperazinyl, 4-piperizyl, 3-aminopyrolizinyl or 3
      aminocyclobutyl group at the 7-position (C-7) of the quinolone skeleton at a
      minimum concentration of 101.8 microg/ml or less. Substitution at position 1, 6
      or 8 of the ring nucleus hardly affected the activity of the compounds with the C
      7 substituted piperazinyl group. The compounds with 7-positioned substituents
      other than the piperazinyl group showed relatively weak activity, and in
      particular those with the 1-aminocyclopropyl group including T-3762 were barely
      positive in concentrations of more than 500 microg/ml. An analysis of the three
      dimensional models of the compounds with the C-7 substituted, nitrogen-containing
      groups revealed that the range of the geometrically optimum distance between the
      nitrogen and the carbon atoms was from 2.98 to 4.98 A for highly active compounds
      and from 2.47 to 2.65 A for weakly active compounds. In conclusion, the C-7
      substituted piperazine moiety of the molecules of already-known fluoroquinolone
      antibiotics may be responsible for the ability to increase cutaneous vascular
      permeability, whereas T-3762 is practically inactive because the free amino
      nitrogen of the 1-aminocyclopropyl group is conformationally present at a shorter
      distance from the carbon atom at position 7 of the ring nucleus.

PMID- 9781840
TI  - Characterization of an apoptosis-inducing factor in Habu snake venom as a
      glycyrrhizin (GL)-binding protein potently inhibited by GL in vitro.
AB  - By means of successive heparin-affinity and glycyrrhizin (GL)-affinity column
      chromatographies (HPLC), a 55 kDa GL-binding protein (gp55) was purified to
      apparent homogeneity from the Superdex P-I fraction of Habu snake venom. This
      gp55 was identified as an apoxin I-like protein, because (i) its 20 N-terminal
      amino acid residues (AHDRNPLEEYFRETDYEEFL) are 95% identical with the
      corresponding sequence of apoxin I (apoptosis-inducing factor, approx. 55 kDa) in
      the venom of the western diamondback rattlesnake; and (ii) L-amino acid oxidase
      (LAO) activity of gp55 is detected when incubated with L-leucine, but not with D
      leucine. GL inhibited the LAO activity of gp55 in a dose-dependent manner, but
      had no effect on the activity of a 65 kDa LAO also purified from Habu snake
      venom. In addition, GL reduced the ability of gp55 to induce the hemolysis of
      sheep red blood cells. These results suggest that GL is a potent inhibitor of
      apoxin I-like proteins in harmful snake venoms.

PMID- 9781842
TI  - Potentiation of acetaminophen hepatotoxicity and mortality by doxapram in mice.
AB  - Whether a single dose of doxapram (DOP) can modulate the acute toxicity and the
      hepatotoxicity induced by acetaminophen (AA) was examined. Pretreatment with DOP
      (40 mg/kg, i.p.) 30 min prior to the administration of AA dose-dependently
      potentiated the lethality of AA in both native mice and mice fasted for 18 h, and
      the potentiating activity was greater in fasted mice than in native mice. The
      hepatotoxicity of AA was assessed by plasma transaminases activity (glutamyl
      oxaloacetic transaminase, GOT; glutamyl pyruvic transaminase, GPT) and the amount
      of plasma lipid peroxides at 6, 12, 18, 24, 36 and 48h after the administration
      of AA and histopathological examination of liver sections at 24 h after the
      administration of AA. DOP (40 mg/kg, i.p.) did not increase the plasma
      transaminase activity or the lipid peroxides level significantly, whereas AA
      administration to DOP-treated animals produced earlier maximal elevation of
      transaminase and lipid peroxide values compared to AA alone. These findings
      indicate that mortality and hepatotoxicity of AA is potentiated by DOP in mice.

PMID- 9781841
TI  - Actions of the novel oral antidiabetic agent HQL-975 in genetically obese
      diabetic db/db mice.
AB  - The hypoglycemic effect of the novel oral agent 3-[4-12-(5-methyl-2-phenyl-oxazol
      4-yl)-ethoxy]-phenyl]-2S-propyla mino-propionic acid (HQL-975) was examined in
      db/db mice with genetically obese non-insulin dependent diabetes mellitus
      (NIDDM). The oral administration of HQL-975 at 3.5 and 35.3 mg/kg/d for 7 d
      decreased the plasma glucose level of these mice in a dose-dependent manner. HQL
      975 also significantly decreased the plasma triglyceride, total cholesterol, non
      esterified fatty acid and insulin levels. In the oral glucose tolerance test, HQL
      975-treated mice showed improved glucose tolerance and decreased endogenous
      insulin secretion. HQL-975 increased glycemic response to exogenous insulin in
      the mice. In the HQL-975-treated db/db mice adipocytes, the glucose uptake,
      insulin binding, and GLUT4 expression were increased compared with those in
      untreated db/db mice adipocytes. These results indicate that HQL-975 improved
      insulin action in db/db mice through receptor and post-receptor effects. In
      conclusion, HQL-975 is a new oral antidiabetic agent with a hypoglycemic effect
      which is associated with an insulin-sensitizing effect. This agent may therefore
      be effective for the treatment of NIDDM.

PMID- 9781843
TI  - Relationship between the skin permeation movement of propranolol and skin
      inflammatory reactions.
AB  - We studied inflammatory reactions induced by dermal application of the beta
      blocker propranolol (PRL) in ethanol to guinea pigs in order to elucidate the
      relation of the reactions with the cumulative PRL permeating amount through the
      stratum corneum or the PRL content in the stripped skin, and to investigate the
      chemical mediators responsible for the reactions. The cumulative PRL permeating
      amount through the stratum corneum increased rapidly up to 2 h after dermal
      application, then increased linearly with time up to 24 h after application.
      Visual observation revealed formation of erythema and edema at the applied site
      of PRL, and histopathological examination revealed infiltration of
      pseudoeosinophiles of dermis and epidermis and degeneration/necrosis of
      epidermis. In general, it was considered that the duration and the extent of
      these reactions were dependent on the PRL dosage and application time. It was
      expected that the cumulative PRL permeating amount through the stratum corneum
      could be used to predict possible inflammatory reactions during development of
      transdermal drug delivery systems. On the other hand, contact of PRL with guinea
      pig skin tissues released histamine, and intradermal injection of PRL caused an
      increase of capillary permeability at the site of application. Also, the
      inhibitory effects of anti-inflammatory agents (diphenhydramine, dexamethasone,
      indomethacin, cyproheptadine hydrochloride, CV3988 and AA-861) to PRL-induced
      erythema formation demonstrated that histamine and prostaglandins were
      responsible for the inflammatory reactions induced by PRL.

PMID- 9781845
TI  - Evaluation of shikonin on granulation tissue formation compared with carrageenan.
AB  - The effect of shikonin (SK) on granulation tissue formation was biochemically
      evaluated and the biological effect of SK on cotton pellet induced granulation
      tissue formation and the induction of hind paw edema was compared with that of
      lambda-carrageenan (carrageenan) in rats. The dry weight of granulation tissue
      formed was increased by SK. The amounts of hemoglobin and hydroxyproline in
      granulation tissue were also increased by SK. These results suggest that SK has
      an enhancing effect on the formation of granulation tissue, accompanied by the
      proliferation of capillaries and the increased production of collagen in rats. SK
      showed mild stimulation toward swelling when injected into the hind paws of rats,
      as did carrageenan, while it showed a marked enhancing effect on granulation
      tissue formation compared with carrageenan. These results suggest that the
      mechanism underlying the biological effect of SK on granulation tissue formation
      is different from that of carrageenan, though the mild stimulation by SK might
      still contribute in part to the enhancing effect on granulation tissue formation.

PMID- 9781844
TI  - Relationship between the structure and cytotoxic activity of asterriquinone, an
      antitumor metabolite of Aspergillus terreus, and its alkyl ether derivatives.
AB  - Asterriquinone (ARQ) is an antitumor metabolite of Aspergillus terreus IFO 6123.
      In this study we synthesized several ARQ alkyl ethers and studied their cytotoxic
      activity against mouse leukemia P388 cells. The dissociation constant was also
      similar among the ARQ monoalkyl ethers. There was a good correlation between the
      hydrophobicity of ARQ monoalkyl ethers estimated by high performance liquid
      chromatography and the intracellular content accumulated for 60 min. ARQ
      monoalkyl ethers were cytotoxic, but ARQ dimethyl ether was not, as previously
      reported. The cytotoxicity of the ARQ monoalkyl ether derivatives was increased
      with extension of the alkyl chain length. The cytotoxicity was closely correlated
      with the intracellular content. The strongest ARQ derivative, ARQ monohexyl ether
      (ARQHex), formed more DNA-interstrand cross-links in the cells than ARQ. After
      treatment of P388 cells with ARQ and ARQHex for 6 h, a nucleosomal ladder
      pattern, as well as the appearance of degraded DNA, observed by flow cytometry,
      indicated that these compounds caused cellular apoptosis. Moreover, ARQ and
      ARQHex accumulated in the cells at the G1 phase of the cell cycle. These results
      indicated that ARQ monoalkyl ethers increased cytotoxicity, according to their
      membrane permeability based on the hydrophobicity, and they caused apoptotic cell
      death, as did ARQ.

PMID- 9781846
TI  - Urinary metabolites of daidzin orally administered in rats.
AB  - In a study on the metabolism of flavonoids, the isoflavone glycoside daidzin was
      orally administered to rats. Urine samples were collected and treated with beta
      glucuronidase and arylsulfatase. Aglycone daidzein (M3) and other three
      metabolites, 3',4',7-trihydroxyisoflavone (M1), 4',7-dihydroxyisoflavanone (M2)
      and 4',7-dihydroxyisoflavan (M4) were isolated from the urine following treatment
      with enzymes. The structures of M1, M2 and M4 were determined on the basis of
      chemical and spectral data.

PMID- 9781848
TI  - Kinetic analysis of the interaction between liposomes and the complement system
      in rat serum: re-evaluation of size-dependency.
AB  - The size of liposomes is considered to be an important factor in determining the
      liposome-complement interaction. In this study, the release of carboxyfluorescein
      (CF) from liposomes was measured continuously for three different diameters (800,
      400 and 200 nm) by changing the liposome concentration from 1 to 1000 nmol/ml. At
      a low liposome concentration range (1-10 nmol/ml), small liposomes (200 nm)
      released CF to a similar extent (approximately 35%) as in the medium (400 nm) and
      large (800 nm) liposomes. The affinity (Km) and capacity (Lmax) of a complement
      system to release liposomally encapsulated CF were estimated by kinetic analysis
      of the liposome-complement interaction. Surprisingly, there was no remarkable
      size dependency in the Km and Lmax in terms of liposome number, although these
      parameters depended on the size of liposomes in terms of lipid concentration.
      These results indicated the possibility that the complement system does not
      discriminate according to liposome size.

PMID- 9781847
TI  - Retention mechanism of imidazoles in connective tissue. III. Aldehyde adduct
      formation of a 4(5H)(or5(4H))-imidazolone product in vitro.
AB  - 2-Methylimidazole (2MI), as well as imidazole, has been thought to undergo cupro
      ascorbate (Cu-VC)-catalyzed oxidative transformation in vitro to become a
      reactive species capable of combining with aldehydes intrinsic to connective
      tissue proteins. We attempted to seize the essence of the above reaction through
      obtaining the structural information of an aldehyde-bonding species. As major
      products from 2MI in the in vitro Cu-VC system, 2-hydroxymethylimidazole
      (2(OH)MI) and 2-methyl-4(5H)(or 5(4H))-imidazolone (2MIone) were identified by
      mass-spectral and chromatographic comparison with the corresponding authentic
      standards synthesized. The in situ addition of acetaldehyde or propionaldehyde as
      a simple protein-aldehyde model to the system resulted in the deducible formation
      of an aldol condensate, 2-methyl-4(or 5)-ethylidene-4(5H)(or 5(4H))-imidazolone
      (2MEIone) or its possible analogue with a propylidene moiety, respectively. The
      authentic compound of 2MIone directly reacted with acetaldehyde and easily
      afforded the products assignable to the isomers of 2MEIone through the ethylidene
      moiety at physiological pH and temperature, whereas neither 2MI or 2(OH)MI
      reacted at all. These results suggest that a 4(5H)(or 5(4H))-imidazolone product,
      although simply a monooxygenated form, is sufficiently reactive to give aldol
      condensation-typed covalent adducts with aldehydes, even under physiological
      conditions, probably having an activated methylene moiety in the ring structure.
      Based on the present results, we discussed the mechanism of the retention of
      imidazole-containing drugs in connective tissue.

PMID- 9781849
TI  - Complement dependent and independent liposome uptake by peritoneal macrophages:
      cholesterol content dependency.
AB  - The uptake mechanisms of liposomes by rat peritoneal macrophages (PMs) were
      investigated. Incubation of liposomes with fresh rat serum enhanced the uptake of
      liposomes depending on the liposome size and cholesterol (CH) content. The
      binding of liposomes was also enhanced by serum, and this increase depended on
      the size and CH content as in the case of liposome uptake, which suggested that
      the binding of opsonized liposomes with PMs govern the extent in liposome uptake.
      The rate constant for the internalization (k(int)) was calculated by measuring
      both uptake and binding. The k(int) cannot explain the variation of liposome
      uptake for different sizes and CH contents. The kint values for liposomes with
      high (44%) and medium (33%) CH contents were constant (2.5 h(-1)) , while those
      for liposomes with low (22%) CH content were significantly elevated (5-9 h(-1)).
      These results indicate the presence of at least two kinds of uptake mechanisms of
      liposomes. Treatment of serum with anti-C3 antibody completely inhibited the
      enhanced uptake of CH-high, large liposomes, which suggested that complement
      receptor-mediated phagocytosis may be an uptake mechanism for CH-high and -medium
      liposomes. In addition, complement-independent enhanced uptake was suggested for
      CH-low liposomes, since no inhibition was observed for CH-low liposomes by anti
      C3 antibody and these liposomes were disintegrated in serum via complement
      independent pathway. These results provided evidence that PMs take up liposomes
      via complement-dependent and independent mechanisms depending on the CH content
      of the liposomes.

PMID- 9781850
TI  - Adjuvant effect of grifolan on antibody production in mice.
AB  - The effects of grifolan (GRN), a gel-forming (1-->6)-branched (1-->3)-beta-D
      glucan, on antibody production were examined. Sera from mice that were injected
      with GRN and trinitrophenyl ovalbumin (TNP-OVA) intraperitoneally showed a
      significantly increased level of anti-TNP IgG. However, injection of TNP-OVA
      alone showed a lower antibody level. Two hundred fifty microg of GRN and 10
      microg of TNP-OVA gave the maximum production of anti-TNP antibody. Enhanced
      antibody production was also observed in the culture supernatant of splenocyte
      obtained from GRN-administered mice. The culture supernatant contained a
      significant amount of nitric oxide (NO) in the case of GRN-administered mice. To
      observe the effect of NO on the antibody production induced by GRN, N-monomethyl
      arginine (NMMA), an inhibitor of NO synthetase, was added to the splenocyte
      cultures. The antibody level of supernatants containing NMMA was higher than that
      of control supernatants. These results suggest that GRN can enhance antibody
      production and that NO induced by stimulation with GRN concomitantly with
      antibody production is a negative factor on the adjuvant activity. Inhibition of
      NO may increase the adjuvant effect of GRN.

PMID- 9781851
TI  - In vitro antioxidant activity of Vietnamese ginseng saponin and its components.
AB  - To elucidate the antioxidant action of Vietnamese ginseng saponin against free
      radial-mediated cellular damage, we examined the effect of Vietnamese ginseng
      saponin on lipid peroxidation in the mouse brain, liver, and liver microsomes by
      using two in vitro free radical generating systems (iron ferrous+ascorbic acid
      and iron ferrous+hydrogen peroxide). Free radical-mediated lipid peroxidation was
      determined by measuring the endogenous and stimulated accumulation of
      thiobarbituric acid reactive substance (TBA-RS). Vietnamese ginseng saponin (0.05
      0.5 mg/ml), as well as vitamin E, significantly inhibited the formation of TBA-RS
      in tissue homogenates. Panax ginseng saponin, at the same concentration range as
      Vietnamese ginseng saponin, also had inhibitory action on free radical-mediated
      lipid peroxidation. However, majonoside-R2, ginsenoside-Rg1 and ginsenoside-Rb1,
      the main saponin components of Vietnamese ginseng saponin fraction, had no effect
      on lipid peroxidation. These results suggest that Vietnamese ginseng exerts a
      protective action against free radical-induced tissue injury and that this effect
      is attributable to minor components rather than the main saponin components
      tested.

PMID- 9781852
TI  - Partial properties of four glycosidases in normal human lens and variations in
      their enzyme activities during aging and with the advance of lens coloration.
AB  - This paper reports the active glycosidases in normal human lenses and their
      partial properties. In addition, variations in their enzyme activities during
      aging and with the advance of lens coloration were also examined. Five
      glycosidases, alpha-glucosidase, beta-D-glucuronidase, N-acetyl-beta-D
      glucosaminidase, beta-D-cellobiosidase, and alpha-L-fucosidase, were detected as
      active glycosidases in the normal human lens. However, the activity of beta-D
      cellobiosidase was considerably low as compared to the other four glycosidases.
      Thus, this enzyme was omitted from this study. The four glycosidases, alpha-D
      glucosidase, beta-D-glucuronidase, N-acetyl-beta-D-glucosaminidase, and alpha-L
      fucosidase, showed that their enzyme activities fell abruptly between the ages of
      40 and 50. Furthermore, the Km values of their enzymes exhibited some variability
      during aging. Namely, the Km values of their enzymes indicated the lowest value
      between the 40 age group and 50 age group, suggesting that the substrate affinity
      became the strongest at these age groups. Then, variations in enzyme activity
      with the advance of lens coloration were examined. In each cases, the specific
      activity of detectable glycosidases in color lenses, white to brown, decreased.
      In particular, the specific activity of enzymes in the brown lens was very low,
      indicating that glycosidases in the brown lens may scarcely display their enzyme
      activities.

PMID- 9781853
TI  - Seasonal variation of glycyrrhizin and isoliquiritigenin glycosides in the root
      of Glycyrrhiza glabra L.
AB  - The time courses of the glycyrrhizin and isoliquiritigenin glycoside contents in
      the thickening roots of licorice, Glycyrrhiza glabra L., have been determined.
      The glycyrrhizin content in 1-year-old roots rapidly increased from October to
      November, whereas the isoliquiritigenin glycoside content increased up to
      October. In 3-year-old plants, although the isoliquiritigenin glycoside content
      rapidly increased from June to July, the glycyrrhizin content did not show any
      significant increase from May to August. The glycyrrhizin content increased
      during the senescence of the aerial parts as well as during the early stage of
      shoot elongation. The incorporation of [14C]mevalonic acid into the glycyrrhizin
      fraction by the root segments was high in May, June and September, and low in
      August and winter. These results indicated that the biosynthesis of glycyrrhizin
      is differently regulated from that of isoliquiritigenin glycoside in the
      thickening root of G. glabra.

PMID- 9781854
TI  - Anti-Helicobacter pylori activity of herbal medicines.
AB  - The extracts of Coptidis japonica (rhizoma), Eugenia caryophyllata (flower),
      Rheum palmatum (rhizoma), Magnolia officinalis (cortex) and Rhusjavanica (galla
      rhois) potently inhibited the growth of Helicobacter pylori (HP). However, these
      herbal extracts showed no inhibitory effect on HP urease except Galla rhois.
      Among the components separated from active herbal extracts by silica gel column
      chromatography, the inhibitory effects of decursinol angelate and decursin on the
      growth of HP were the most potent, followed by magnolol, berberine, cinnamic
      acid, decursinol and gallic acid. Minimum inhibitory concentrations (MICs) of
      decursin and decursinol angelate were 6-20 microg/ml.

PMID- 9781855
TI  - Anti-tumor-promoting activity of diterpenes from Excoecaria agallocha.
AB  - To search for possible anti-tumor-promoters, we carried out the primary screening
      of seventeen diterpenes (1-17) isolated from the resinous wood of Excoecaria
      agallocha (Euphorbiaceae) using an in vitro synergistic assay system. Of these
      diterpenes, ent-16-hydroxy-3-oxo-13-epi-manoyloxide (5), (13R,14R)-ent
      8alpha,13;14,15-diepoxy-13-epi- labda-3beta-ol (8) ent-3beta-hydroxy-15-beyeren-2
      one (10) and ent-15-hydroxy-labda-8(17),13E-dien-3-one (14) exhibited significant
      inhibitory effects on Epstein-Barr virus (EBV) activation induced by the tumor
      promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Furthermore, 10 exhibited
      remarkable anti-tumor-promoting activity in vivo on a two-stage carcinogenesis
      test of mouse tumor using 7,12-dimethylbenz[a]-anthracene (DMBA) as an initiator
      and TPA as a promoter.

PMID- 9781856
TI  - Studies on inhibitory activities of fukiic acid esters on germination, alpha
      amylase and carboxypeptidase A.
AB  - Fukinolic acid (1) and cimicifugic acid A (2), caffeic acid analogs, as well as
      rosmarinic acid (3) and caffeic acid (4) showed inhibition on seed germination
      and seedling growth. The potency of 1 and 2 was comparable with that of 3.
      Compounds 1 and 2 also showed strong inhibitory activities as well as 3 and 4 on
      alpha-amylase. The activity of 1 was higher than that of acarbose used as a
      positive control, and its 50% inhibitory concentration (IC50) was 2.41 x 10(-5)
      M. Compounds 1 and 2 also showed inhibitory activities strong as 3 and stronger
      than 4 on carboxypeptidase A. The activities of 1 and 2 were higher than that of
      1, 10-phenanthroline used as a positive control.

PMID- 9781857
TI  - Changes in serum levels of sialoglycoproteins in mice exposed to UV-B radiation.
AB  - In the acute phase reaction, hepatocytes in the liver are activated and increase
      the plasma levels of acute phase reactants. Our previous study has shown that
      plasma sialic acid, an acute phase reactant, was increased following exposure of
      mice to UV-B radiation. Plasma sialic acid is derived from many plasma
      components. To clarify the type of plasma sialic acid that is increased by
      exposure to UV-B radiation, we performed two-dimensional electrophoresis and
      staining for sialic acid. Consequently, the increases in haptoglobin and
      hemopexin were marked and 90% or more of the increased sialic acid was derived
      from these two glycoproteins after exposure to UV radiation. The increase in
      alpha1-acid glycoprotein levels was slight and did not contribute to the total
      increase in plasma sialic acid after exposure to UV radiation. Plasma levels of
      several proteins including antichymotrypsin (ACT), were reduced following
      exposure to UV radiation. The discrepancy between our results and published ones
      regarding ACT levels are discussed in terms of the type of cytokine.

PMID- 9781858
TI  - Effect of cytokinin 4PU30 on organ differentiation and dihydroisocoumarin
      production in amacha callus cultures.
AB  - Effect of a suitable combination of 1-naphthaleneacetic acid (NAA) and cytokinin
      N-(2-chloro-4-pyridyl)-N'-phenylurea (4PU30) concentrations, regarding organ
      differentiation and dihydroisocoumarin production, was examined in Hydrangea
      macrophylla var. thunbergii callus cultures. The callus cultured in a Linsmaier
      Skoog medium containing 10(-5) M NAA and 10(-5) M 4PU30 under a light condition
      gave the highest level for callus growth, shoot formation, and phyllodulcin 8-O
      glucoside content.

PMID- 9781859
TI  - Marginal leakage in class II-restorations after use of ceramic-inserts luted with
      different materials.
AB  - The efficiency of using prefabricated ceramic inlays to prevent microleakage has
      been discussed in different investigations. The purpose of this study was to
      evaluate the marginal microleakage of a new glass ceramic inlay system in
      combination with two different composite luting materials and one polyacid
      modified composite, respectively. Standardized class II cavities (n = 60) were
      filled with (1) Empress inlays fixed with a highly viscous luting composite as a
      control group, and with glass ceramic inlays (Cerana) in combination with (2) a
      highly viscous luting composite, (3) a low-viscous luting composite and (4) a
      polyacid-modified composite, respectively. After thermocycling the marginal
      quality was analysed with scanning electron microscopy, and the dye penetration
      along the cavity walls was measured. The use of the Cerana inlays with a polyacid
      modified composite resin did not reveal a good marginal adaptation. However, the
      combination of the Cerana and the Empress inlays with the highly viscous
      composite exhibited a comparable marginal fit. Within the limitations of an in
      vitro study it is concluded that the combination of the new glass ceramic inlays
      with a polyacid-modified composite cannot be recommended for clinical use.

PMID- 9781860
TI  - Leached components from dental composites in oral simulating fluids and the
      resultant composite strengths.
AB  - The aim of this study was to analyse the leached moieties of dental composites
      after storage in ethanol and organic acids of plaque and further evaluate the
      resultant effect on the diametral tensile strength (DTS) of the composites. Three
      commercial composites were used: Bis-GMA-based Z100, Bis-GMA/UDMA-based
      Heliomolar, and Bis-MPEPP-based Marathon One. The solutions used were: 99.9%
      acetic acid, 99% propionic acid and 75% ethanol. Specimens (4 mm diam. x 2 mm
      thick) were stored at 37 degrees C in 3 mL of solution for up to 30 days. Gas
      chromatography/mass spectrometry was used to characterize the leached moieties
      and DTS of the specimens after immersion was evaluated. Data were analysed using
      ANOVA and Tukey LSD test. The eluted substances were not all the same in
      different solutions and composites but mostly increased with immersion time, and
      included diluents (TEGDMA and decamethacrylate) and some additives, such as an
      ultra-violet stabilizer (TINUVINP), plasticizers (dicyclohexyl phthalate and
      bis(2-ethylhexyl) phthalate), initiator (triphenyl stibine), coupling agent
      (gamma-methacryloxypropyl trimethoxysilane), and phenyl benzoate. The chief
      polymerizing monomers were not found. More kinds of components were found in the
      acetic acid and ethanol groups studied. The fewest kinds and quantities of
      leached moieties were found for Bis-GMA specimens and then Bis-GMA/UDMA ones,
      most of which are diluent agents. Bis-MPEPP specimens leached the most
      substances, which were composed mostly of a short phenyl group chain structure.
      The BisGMA composite showed the highest DTS (54.8 +/- 5.7 MPa), which was not
      greatly affected by the length of storage. Bis-GMA/UDMA (36.2 +/- 6.8 MPa) and
      Bis-MPEPP (26.1 +/- 4.5 MPa) composites were significantly reduced (P < 0.05)
      after 30 days storage in the ethanol (35-50%), in the propionic acid (25-30%),
      and in the acetic acid (40-60%). Irreversible processes such as the leaching of
      components occur in fluids simulating an oral environment, which may contribute
      to irreversible material degradation, especially for non-Bis-GMA-based
      composites.

PMID- 9781861
TI  - The effect of light premature occlusal contact on tooth pain threshold in humans.
AB  - The purpose of this study was to assess the influence of an experimentally
      induced light premature occlusal contact on tooth sensation. This assessment
      involved monitoring the electric tooth pain threshold (TPT) at multiple times
      before and after altering the occlusal contact. This alteration was produced by
      placing high inlays, which were measured with a custom made measuring device in
      maximum intercuspation. Data were collected on 10 teeth in 5 subjects, all whom
      were male and between the ages of 24 and 30 years. The contact area of the high
      inlays varied from 75 microm to 193 microm. The TPT changes in these teeth ranged
      from -43 to +21% of their baseline level. Seven of these teeth showed a
      significant decrease (P < 0.05) in the TPT, one showed an increase and two did
      not show a significant change. Two of the teeth with a decreased TPT had cold
      water triggered occlusal pain, and 2 teeth had only occlusal pain. After several
      inlay adjustments to eliminate interference in maximum intercuspation, all tested
      teeth returned to their TPT baseline level and all symptoms disappeared. These
      results suggested that a light premature occlusal contact may change tooth
      sensation.

PMID- 9781862
TI  - Perfusing dentine with horse serum or physiologic saline: its effect on adhesion
      of dentine bonding agents.
AB  - Freshly prepared dentine specimens of human teeth were perfused with either horse
      serum or physiologic saline. After application of AllBond2, ART Bond, Syntac or
      an experimental dentine bonding agent called P-Bond, a composite cylinder was
      added and cured at the same time. After 1500 thermal cycles with constant
      imitation of intrapulpal pressure, the shear bond strengths were measured.
      Resulting shear bond strength values were analysed with Students t-test or Mann
      Whitney Test. The values for AllBond2 were not significantly different. The
      values for ART Bond (P < 0.05) and for Syntac (P < 0.05) were significantly
      higher if the dentine was perfused with horse serum. For P-Bond (P < 0.001) the
      values were significantly higher if the dentine was perfused with physiologic
      saline. According to these results it does not seem to be appropriate to take a
      clear decision as to which of the two perfusing media investigated might be more
      suitable to imitate in vivo conditions.

PMID- 9781863
TI  - A polysomnographic study on masticatory and tongue muscle activity during
      obstructive and central sleep apnea.
AB  - Masticatory and tongue muscle activity was examined polysomnographically in 14
      patients with sleep apnea syndrome and six snorers. The all-night
      polysomnographic recordings included electromyograms (EMG) of the genioglossal,
      the masseter and the inferior head of the lateral pterygoid muscles, nasal
      airflow and thoracoabdominal respiratory effort. The apneas were defined and
      classified into three types (obstructive, central and mixed). EMG amplitudes of
      each muscle were measured before, during and after the obstructive and central
      apneas. In the apnea patients the three muscles showed significantly lower EMG
      amplitudes during the obstructive apnea than before the apnea, and then
      significantly higher amplitudes after the apnea. These findings indicate that the
      hypotonia of the muscles during sleep can result in obstructive apnea. There was
      no significant difference in the pattern of muscle activity during obstructive
      apnea between the apnea patients and the snorers. On the other hand, a decrease
      in the mean EMG amplitude during the central apnea was not observed. It is
      suggested that central apnea occurs independently of masticatory and tongue
      muscle activity.

PMID- 9781864
TI  - Attempted evaluation of three porcelain repair systems--what are we really
      testing?
AB  - Porcelain restorations are widely used in restorative dentistry with general
      success. On occasion however, fracture of the porcelain occurs. Sometimes a
      repair may be attempted using resin composite and one of the many bonding systems
      available. This in vitro investigation sought to determine and compare the shear
      bond strengths between a visible light-cured resin composite (Prisma TPH) and
      dental porcelain (Matchmaker Porcelain) for three different bonding systems
      (Scotchbond Multipurpose Plus (SMP); One-Step (OS); DenTASTIC (D)) with a view to
      conducting a larger study to assist in material selection. All measurements were
      performed one week following the preparation and storage of specimens in
      distilled water, at 37 degrees C, using a Universal Testing Machine at a
      crosshead speed of 0.5 mm/min. Although the mean shear bond strengths differed
      significantly (P < 0.05) (OS > SMP) and the Weibull modulus value of SMP was
      significantly (P < 0.05) lower than both OS and D the almost exclusive cohesive
      mode of failure observed, within the porcelain itself, suggested that the test
      was more a reflection of the quality of the underlying porcelain than the union
      under investigation. It was thus concluded that the shear bond strength test
      employed here, and in other studies did not truly reflect the shear bond strength
      at the porcelain/composite interface and that a more meaningful test should be
      developed. The observed cohesive failure may account for repeated clinical
      failures of porcelain repairs where bonding to an inherently flawed porcelain
      structure inevitably results in further failure.

PMID- 9781865
TI  - Changes on storage of polyacid-modified composite resins.
AB  - Two polyacid-modified composite resins, Dyract and Compoglass, have been studied
      for water-uptake on storage in three aqueous media, namely pure water, 0.9% NaCl
      and 1 M NaCl at 37 degrees C, and the results compared with those of a
      conventional composite resin, Pekafill. The equilibrium water-uptake of Dyract
      and Compoglass varied depending on time of cure and ionic strength of the storage
      medium. This latter finding contrasted with that for Pekafill, where equilibrium
      water content showed almost no variation with ionic strength of the storage
      medium. Uptake of water was always greater in Dyract and Compoglass than in
      Pekafill, reflecting the role of water in promoting the later neutralization
      reaction in these materials and its further role in hydrating the ionic products
      of that reaction. Despite this and other evidence of neutralization, specimens of
      Dyract and Compoglass stored in wet conditions (0.9% NaCl) showed no change in
      compressive strength on storage from 24 h to 30 days, a result similar to that
      reported previously for Dyract alone for flexural strength for times up to 1
      year. By contrast, specimens of Dyract and Compoglass stored in dry air at 37
      degrees C, and therefore unable to undergo any neutralization, showed an increase
      in compressive strength of between 40 and 70 MPa by 30 days that was significant
      at P < 0.01.

PMID- 9781866
TI  - Viscoelastic properties of tissue conditioners--influence of molecular weight of
      polymer powders and powder/liquid ratio and the clinical implications.
AB  - The effect of the molecular weight of polymer powders and the polymer
      powder/liquid ratio on the viscoelastic properties after gelation of tissue
      conditioners was studied by means of a stress relaxation test. The results are
      summarized as follows. The lower-molecular-weight polymer powders produced the
      larger flow after gelation especially at long times. The use of a lower
      powder/liquid ratio produced a greater flow after gelation at both short times
      and long times. The difference in the molecular weight of polymer powders and the
      powder/liquid ratio was found to have no influence on changes in viscoelastic
      properties with the passage of time. It would be possible to control the
      viscoelastic properties of tissue conditioners suitable for each clinical purpose
      by making variations in composition and structure.

PMID- 9781867
TI  - Effects of honey consumption on enamel microhardness in normal versus xerostomic
      patients.
AB  - The aim was to investigate the effect of honey on the microhardness of enamel in
      normal and xerostomic patients. Normal subjects and patients who were xerostomic
      after neck irradiation, wearing prosthetic appliances with slabs of human enamel
      inserted, were asked to consume a single teaspoonful of pure honey, pH 3.9.
      Measurements of the saliva pH were taken before, during and after a 5 min
      exposure to the honey. The pH of the honey-saliva mixtures decreased
      significantly from about 6 to 4 in both groups, returning to the baseline pH
      after the mixture was swallowed. The initial microhardness of the surface of the
      enamel slabs decreased significantly after consumption of a teaspoonful of the
      honey in the subjects with a regular saliva flow, whereas in the irradiated dry
      mouth patients, no enamel microhardness decrease occurred. The supposed
      solubility-reducing factor present in honey which, according to the literature
      remains active in the absence of saliva, but will be inactivated by salivary
      enzymes, gives some support to the hypothesis that honey is less cariogenic in
      dry-mouth subjects. The absence of adequate controls in the present study
      prevents the investigation of how specific this effect is to honey.

PMID- 9781868
TI  - Autocorrelation of acoustic signals from the temporomandibular joint.
AB  - Although there have been many investigations of TMJ sounds in the time and
      frequency domains, no previous reports have been found of investigations of the
      autocorrelation spectra of these sounds. In the present study, TMJ sounds were
      digitized at 1.7 kHz and 300 ms samples containing either clicks (single short
      duration sounds), crepitus (long duration continuous sounds) or creaks (a series
      of two or more clicks) were selected. These samples were compared with sounds of
      known origin: tooth impact sounds, frictional sounds elicited by scratching the
      head, and bruxing sounds resulting from stick-slip friction as teeth were slid
      against one another under high pressure. There were clear qualitative and
      quantitative differences between the autocorrelation spectra of the three types
      of TMJ sounds. Clicks were similar to tooth impact contact sounds, creaks were
      similar to the bruxing sounds, and crepitus was similar to the scratching sounds.
      The repetition rate of creaks was 16 Hz (s.d. 9 Hz), this being similar to the
      resonance of the mandible about the condylar axis. It is suggested that the
      creaks are due to stick-slip friction in the lower joint compartment of the TMJ.

PMID- 9781869
TI  - A clinical and radiographic study of 25 autotransplanted third molars.
AB  - This paper is a report on 25 autotransplantations of third molars with complete
      root formations. The study consists of 23 patients in whom 25 third molars were
      transplanted. The mean age was 29.6 years (range 20-54). In nine cases third
      molars were directly transplanted into the new socket. In 11 cases the sockets
      were widened and made deeper with a bur. In five cases the recipient beds were
      made by splitting osteotomy of the alveolar region. The transplanted third molars
      were stabilized with silk sutures, resin, wire splint or circumferential wiring
      for 1-6 weeks. Two-three weeks after transplantation, the root canals were
      treated and filled. After operation, the marginal and the periapical conditions
      were examined clinically and radiographically. The transplanted teeth clinically
      appeared to become firmer with the passage of time. Progressive root resorption
      was not found and good results were obtained. This study shows that
      autotransplantation of third molars with complete root formation produces an
      acceptable result using the procedures outlined.

PMID- 9781870
TI  - Determining the accuracy of stock and custom tray impression/casts.
AB  - A study was conducted to evaluate the accuracy of casts made from stock tray and
      custom tray impressions using polysiloxane impression material. The results
      indicate that all casts distort but that impressions made from custom trays were
      more accurate and consistent in reproduction than were stock tray impressions.

PMID- 9781872
TI  - DNA repair in Mycobacterium tuberculosis. What have we learnt from the genome
      sequence?
AB  - The genome sequence of Mycobacterium tuberculosis was analysed by searching for
      homologues of genes known to be involved in the reversal or repair of DNA damage
      in Escherichia coli and related organisms. Genes necessary to perform nucleotide
      excision repair (NER), base excision repair (BER), recombination, and SOS repair
      and mutagenesis were identified. In particular, all of the genes known to be
      directly involved in the repair of oxidative and alkylative damage are present in
      M. tuberculosis. In contrast, we failed to identify homologues of genes involved
      in mismatch repair. This finding has potentially significant implications with
      respect to genome stability, strain variability at repeat loci and the emergence
      of chromosomally encoded drug resistance mutations.

PMID- 9781871
TI  - Global regulation by the small RNA-binding protein CsrA and the non-coding RNA
      molecule CsrB.
AB  - Csr (carbon storage regulator) is a recently discovered global regulatory system
      that controls bacterial gene expression post-transcriptionally. Its effector is a
      small RNA-binding protein referred to as CsrA or, in phytopathogenic Erwinia
      species, RsmA (repressor of stationary phase metabolites). Numerous genes whose
      expression occurs in the stationary phase of growth are repressed by csrA/rsmA,
      and csrA activates certain exponential-phase metabolic pathways. Glycogen
      synthesis and catabolism, gluconeogenesis, glycolysis, motility, cell surface
      properties and adherence are modulated by csrA in Escherichia coli, while the
      production of several secreted virulence factors, the plant hypersensitive
      response elicitor HrpN(Ecc) and, potentially, other secondary metabolites are
      regulated by rsmA in Erwinia carotovora. CsrA represses glycogen synthesis by
      binding to and destabilizing glgCAP mRNA and is hypothesized to repress other
      genes by a similar mechanism. The second component of the Csr system is CsrB
      (AepH in Erwinia species), a non-coding RNA molecule that forms a large globular
      ribonucleoprotein complex with approximately 18 CsrA subunits and antagonizes the
      effects of CsrA in vivo. Highly repeated sequence elements found within the loops
      of predicted stem-loops and other single-stranded segments of CsrB RNA may
      facilitate CsrA binding. Current information supports a model in which CsrA
      exists in an equilibrium between CsrB and CsrA-regulated mRNAs, which predicts
      that CsrB levels may be a key determinant of CsrA activity in the cell. The
      presence of csrA homologues in phylogenetically diverse species further suggests
      that this novel kind of regulatory system is likely to play a broad role in
      modulating eubacterial gene expression.

PMID- 9781873
TI  - Codon usages in different gene classes of the Escherichia coli genome.
AB  - A new measure for assessing codon bias of one group of genes with respect to a
      second group of genes is introduced. In this formulation, codon bias correlations
      for Escherichia coli genes are evaluated for level of expression, for contrasts
      along genes, for genes in different 200 kb (or longer) contigs around the genome,
      for effects of gene size, for variation over different function classes, for
      codon bias in relation to possible lateral transfer and for dicodon bias for some
      gene classes. Among the function classes, codon biases of ribosomal proteins are
      the most deviant from the codon frequencies of the average E. coli gene. Other
      classes of 'highly expressed genes' (e.g. amino acyl tRNA synthetases,
      chaperonins, modification genes essential to translation activities) show less
      extreme codon biases. Consistently for genes with experimentally determined
      expression rates in the exponential growth phase, those of highest molar
      abundances are more deviant from the average gene codon frequencies and are more
      similar in codon frequencies to the average ribosomal protein gene. Independent
      of gene size, the codon biases in the 5' third of genes deviate by more than a
      factor of two from those in the middle and 3' thirds. In this context, there
      appear to be conflicting selection pressures imposed by the constraints of
      ribosomal binding, or more generally the early phase of protein synthesis (about
      the first 50 codons) may be more biased than the complete nascent polypeptide. In
      partitioning the E. coli genome into 10 equal lengths, pronounced differences in
      codon site 3 G+C frequencies accumulate. Genes near to oriC have 5% greater codon
      site 3 G+C frequencies than do genes from the ter region. This difference also is
      observed between small (100-300 codons) and large (>800 codons) genes. This
      result contrasts with that for eukaryotic genomes (including human,
      Caenorhabditis elegans and yeast) where long genes tend to have site 3 more AT
      rich than short genes. Many of the above results are special for E. coli genes
      and do not apply to genes of most bacterial genomes. A gene is defined as alien
      (possibly horizontally transferred) if its codon bias relative to the average
      gene exceeds a high threshold and the codon bias relative to ribosomal proteins
      is also appropriately high. These are identified, including four clusters
      (operons). The bulk of these genes have no known function.

PMID- 9781875
TI  - A five-nucleotide sequence protects DNA from exonucleolytic degradation by AddAB,
      the RecBCD analogue of Bacillus subtilis.
AB  - Homologous recombination in Bacillus subtilis requires the product of the addA
      and addB genes, the AddAB enzyme. This enzyme, which is both a helicase and a
      powerful nuclease, is thought to be the counterpart of the Escherichia coli
      RecBCD enzyme. From this analogy, it is expected that the nuclease activity of
      AddAB can be downregulated by a specific DNA sequence, which would correspond to
      the chi site in E. coli. Using protection of linear double-stranded DNA as a
      criterion, we identified the five-nucleotide sequence 5'-AGCGG-3', or its
      complement 5'-CCGCT-3', as being sufficient for AddAB nuclease attenuation. We
      have shown further that this attenuation occurs only if the sequence is properly
      oriented with respect to the translocating AddAB enzyme. Finally, inspection of
      the complete B. subtilis genome revealed that this five-nucleotide sequence is
      over-represented and is, in a majority of cases, co-oriented with DNA
      replication. Based on these observations, we propose that 5'-AGCGG-3', or its
      complement, is the B. subtilis analogue of the E. coli chi sequence.

PMID- 9781874
TI  - Characterization of the geranylgeranyl transferase type I from
      Schizosaccharomyces pombe.
AB  - The Schizosaccharomyces pombe cwg2+ gene encodes the beta-subunit of
      geranylgeranyl transferase I (GGTase I), which participates in the post
      translational C-terminal modification of several small GTPases, allowing their
      targeting to the membrane. Using the two-hybrid system, we have identified the
      cwp1+ gene that encodes the alpha-subunit of the GGTase I. cwp1p interaction with
      cwg2p was mapped to amino acids 1-244 or 137-294 but was not restricted to amino
      acids 137-244. The genomic cwp1+ was isolated and sequenced. It has two putative
      open reading frames of 677 and 218 bp, separated by a 51 bp intron. The predicted
      amino acid sequence shows significant similarity to GGTase I alpha-subunits from
      different species. However, complementation of Saccharomyces cerevisiae ram2-1
      mutant by overexpressing the cwp1+ gene was not possible. Expression of both
      cwg2+ and cwp1+ in Escherichia coli allowed 'in vitro' reconstitution of the
      GGTase I activity. S. pombe cells expressing the mutant enzyme containing the
      cwg2-1 mutation do not grow at 37 degrees C, but the growth defect can be
      suppressed by the addition of sorbitol. Actin immunostaining of the cwg2-1 mutant
      strain grown at 37 degrees C showed an abnormal distribution of actin patches.
      The cwg2-1 mutation was identified as a guanine to adenine substitution at
      nucleotide 604 of the coding region, originating the change A202T in the cwg2p.
      Deletion of the cwg2 gene is lethal; delta cwg2 spores can divide two or three
      times before losing viability. Most cells have aberrant morphology and septation
      defects. Overexpression of the rho1G15VC199R double-mutant allele in S. pombe
      caused loss of polarity but was not lethal and did not render the (1-3)beta-D
      glucan synthase activity independent of GTP. Therefore, geranylgeranylation of
      rho1p is required for the appropriate function of this GTPase.

PMID- 9781876
TI  - hpaA mutants of Xanthomonas campestris pv. vesicatoria are affected in
      pathogenicity but retain the ability to induce host-specific hypersensitive
      reaction.
AB  - Xanthomonas campestris pv. vesicatoria is the causal agent of bacterial spot
      disease on pepper and tomato plants. We reported previously that the main hrp
      (hypersensitive reaction and pathogenicity) gene cluster in X. c. pv. vesicatoria
      contains six transcription units, designated hrpA to hrpF. We present here the
      sequence of the hrpD operon and an analysis of non-polar mutants in each of the
      six genes. Three genes, hrcQ, hrcR and hrcS, are predicted to encode conserved
      components of type III protein secretion systems in plant and mammalian
      pathogenic bacteria. For hrpD5 and hrpD6, homologues have only been found in
      Ralstonia solanacearum. Interestingly, the hrpD operon contains one gene, hpaA
      (for hrp-associated), which is specifically required for disease development.
      hpaA mutants are affected in pathogenicity, but retain in part the ability to
      induce avirulence gene-mediated, host-specific hypersensitive reaction (HR). In
      addition, HpaA was found to contain two functional nuclear localization signals,
      which are important for the interaction with the plant. We propose that HpaA is
      an effector protein that may be translocated into the host cell via the Hrp
      secretion pathway.

PMID- 9781877
TI  - Characterization of the Erwinia chrysanthemi expI-expR locus directing the
      synthesis of two N-acyl-homoserine lactone signal molecules.
AB  - The plant pathogen Erwinia chrysanthemi produces three acyl-homoserine lactones
      (acyl-HSLs). One has been identified as N-(3-oxohexanoyl)-homoserine lactone
      (OHHL), and the two others were supposed to be N (hexanoyl)-homoserine lactone
      (HHL) and N-(decanoyl)-homoserine lactone (DHL). The genes for a quorum-sensing
      signal generator (expI) and a response regulator (expR) were cloned. These genes
      are convergently transcribed and display high similarity to the expI-expR genes
      of Erwinia carotovora. ExpI is responsible for both OHHL and HHL production.
      Inactivation of expl had little effect on pectinase synthesis in E. chrysanthemi,
      as expression of only two of the pectate lyase genes, pelA and pelB, was
      decreased. E. chrysanthemi expR mutants still produced acyl-HSL and pectinases.
      However, gel shift and DNAse I footprinting experiments showed that the purified
      E. chrysanthemi ExpR protein binds specifically to the promoter regions of the
      five major pel genes. Addition of OHHL modified the ExpR-DNA bandshift profiles,
      indicating that ExpR interacts with OHHL and binds to DNA in different ways,
      depending on the OHHL concentration. Localization of the ExpR binding sites just
      upstream of promoter regions suggests that ExpR functions as an activator of pel
      expression in the presence of OHHL. The absence of a phenotype in expR mutants
      strongly suggests that at least an additional interchangeable ExpR homologue
      exists in E. chrysanthemi. Finally, transcription of expI::uidA and expR::uidA
      fusions is dependent on the population density, suggesting the existence of a
      quorum-sensing hierarchy in E. chrysanthemi. These results suggest that the expI
      expR locus is part of a complex autoregulatory system that controls quorum
      sensing in E. chrysanthemi.

PMID- 9781878
TI  - Integration of the quorum-sensing system in the regulatory networks controlling
      virulence factor synthesis in Erwinia chrysanthemi.
AB  - The expI-expR locus drives a quorum-sensing system in the phytopathogenic
      bacterium, Erwinia chrysanthemi. Purified ExpR, an N-acyl homoserine lactone
      responsive regulatory protein, binds to the promoter/operator region of the expI
      and expR genes. DNase I footprinting experiments showed that ExpR protects the
      regions between -66 and -40 from the P1 transcription initiation site of expl and
      between -54 and -18 from the expR transcription initiation site P1. The protected
      region overlaps the two expR promoters, P1 and P2, suggesting that ExpR exerts a
      negative control on its own gene expression. This assertion is reinforced by the
      fact that the addition of OHHL dissociates the ExpR-expR DNA complex. In
      contrast, the location of the ExpR binding site on the expI gene suggests an
      activator function, as reported for the pel genes. Moreover, ExpR is able to
      induce DNA bending. In vivo and in vitro studies revealed that CRP functions as
      an activator of expR expression, but as a repressor of expI transcription. A
      second level of control of expR and expI occurs through the PecS repressor, a
      regulator of pectinase synthesis. PecS represses expI expression, while ExpR
      activates pecS transcription, suggesting the existence of a mutual control
      between pecS and the expI-expR system in E. chrysanthemi. Regulation of pectinase
      synthesis in soft rot Erwinia appears to be a complex network of multiple cross
      acting regulatory elements. A model that integrates these regulatory elements is
      proposed.

PMID- 9781879
TI  - Synthesis of the A-band polysaccharide sugar D-rhamnose requires Rmd and WbpW:
      identification of multiple AlgA homologues, WbpW and ORF488, in Pseudomonas
      aeruginosa.
AB  - Pseudomonas aeruginosa is capable of producing various cell-surface
      polysaccharides including alginate, A-band and B-band lipopolysaccharides (LPS).
      The D-mannuronic acid residues of alginate and the D-rhamnose (D-Rha) residues of
      A-band polysaccharide are both derived from the common sugar nucleotide precursor
      GDP-D-mannose (D-Man). Three genes, rmd, gmd and wbpW, which encode proteins
      involved in the synthesis of GDP-D-Rha, have been localized to the 5' end of the
      A-band gene cluster. In this study, WbpW was found to be homologous to
      phosphomannose isomerases (PMIs) and GDP-mannose pyrophosphorylases (GMPs)
      involved in GDP-D-Man biosynthesis. To confirm the enzymatic activity of WbpW,
      Escherichia coli PMI and GMP mutants deficient in the K30 capsule were
      complemented with wbpW, and restoration of K30 capsule production was observed.
      This indicates that WbpW, like AlgA, is a bifunctional enzyme that possesses both
      PMI and GMP activities for the synthesis of GDP-D-Man. No gene encoding a
      phosphomannose mutase (PMM) enzyme could be identified within the A-band gene
      cluster. This suggests that the PMM activity of AlgC may be essential for
      synthesis of the precursor pool of GDP-D-Man, which is converted to GDP-D-Rha for
      A-band synthesis. Gmd, a previously reported A-band enzyme, and Rmd are predicted
      to perform the two-step conversion of GDP-D-Man to GDP-D-Rha. Chromosomal mutants
      were generated in both rmd and wbpW. The Rmd mutants do not produce A-band LPS,
      while the WbpW mutants synthesize very low amounts of A band after 18 h of
      growth. The latter observation was thought to result from the presence of the
      functional homologue AlgA, which may compensate for the WbpW deficiency in these
      mutants. Thus, WbpW AlgA double mutants were constructed. These mutants also
      produced low levels of A-band LPS. A search of the PAO1 genome sequence
      identified a second AlgA homologue, designated ORF488, which may be responsible
      for the synthesis of GDP-D-Man in the absence of WbpW and AlgA. Polymerase chain
      reaction (PCR) amplification and sequence analysis of this region reveals three
      open reading frames (ORFs), orf477, orf488 and orf303, arranged as an operon.
      ORF477 is homologous to initiating enzymes that transfer glucose 1-phosphate onto
      undecaprenol phosphate (Und-P), while ORF303 is homologous to L
      rhamnosyltransferases involved in polysaccharide assembly. Chromosomal mapping
      using pulsed field gel electrophoresis (PFGE) and Southern hybridization places
      orf477, orf488 and orf303 between 0.3 and 0.9 min on the 75 min map of PAO1,
      giving it a map location distinct from that of previously described
      polysaccharide genes. This region may represent a unique locus within P.
      aeruginosa responsible for the synthesis of another polysaccharide molecule.

PMID- 9781880
TI  - Gyrase and Topo IV modulate chromosome domain size in vivo.
AB  - In bacteria, DNA supercoil movement is restricted to subchromosomal regions or
      'domains.' To elucidate the nature of domain boundaries, we analysed reaction
      kinetics for gammadelta site-specific resolution in six chromosomal intervals
      ranging in size from 14 to 90 kb. In stationary cultures of Salmonella
      typhimurium, resolution kinetics were rapid for both short and long intervals,
      suggesting that random stationary barriers occur with a 30% probability at
      approximately 80 kb intervals along DNA. To test the biochemical nature of domain
      barriers, a genetic screen was used to look for mutants with small domains. Rare
      temperature-sensitive alleles of DNA gyrase and Topo IV (the two essential type
      II topoisomerases) had more supercoil barriers than wild-type strains in all
      growth states. The most severe gyrase mutants were found to have twice as many
      barriers in growing cells as wild type throughout a 90 kb interval of the
      chromosome. We propose that knots and tangles in duplex DNA restrain supercoil
      diffusion in living bacteria.

PMID- 9781881
TI  - The effect of oxygenated mycolic acid composition on cell wall function and
      macrophage growth in Mycobacterium tuberculosis.
AB  - There are three major structural classes of mycolic acids in the cell envelope of
      Mycobacterium tuberculosis (MTB): alpha-, methoxy- and ketomycolate. The two
      oxygen-containing classes are biosynthetically related through a common alpha
      methyl hydroxymycolate intermediate. BCG strains that fail to produce
      methoxymycolate and instead produce only keto- and alpha-mycolic acids show
      apparent defects in the O-methyltransferase MMAS-3. Overproduction of MMAS-3 from
      MTB resulted in a complete replacement of ketomycolate by methoxymycolate in both
      BCG and MTB. In vitro growth of these recombinant strains lacking ketomycolate
      was impaired at reduced temperatures but appeared to be normal at 37 degrees C.
      Glucose uptake was significantly decreased in such strains, but uptake of
      chenodeoxycholate and glycine was unaffected. Although sensitivity to INH
      remained unchanged, these cells were found to be hypersensitive to ampicillin and
      rifampicin. Infectivity of BCG and H37Rv wild type or MMAS-3 overproducers in THP
      1 cells was somewhat affected, but the ability of the strains lacking
      ketomycolate to grow within this macrophage-like cell line was severely
      compromised. In vivo labelling of mycolic acids during growth of H37Rv within THP
      1 cells revealed a substantial increase in ketomycolate and alphamycolate
      synthesized by intracellularly grown mycobacteria. These results establish a
      critical role for mycolate composition in proper cell wall function during the
      growth of MTB in vivo.

PMID- 9781882
TI  - Processing of the pectate lyase PelI by extracellular proteases of Erwinia
      chrysanthemi 3937.
AB  - Erwinia chrysanthemi causes soft rot on various plants. The maceration of plant
      tissues is mainly due to the action of endopectate lyases. The E. chrysanthemi
      strain 3937 produces eight endopectate lyases (PelA, PelB, PelC, PelD, PelE,
      PelI, PelL and PelZ) that are secreted by the Out pathway. The necrotic response
      elicited by the wild-type E. chrysanthemi strain on tobacco leaves is due to an
      extracellular protein secreted by the Out machinery. Purification of the active
      factor revealed that it corresponds to a pectate lyase presenting immunological
      cross-reaction with PelI. Analysis of pelI and out mutants indicated that the
      necrosis-inducing pectate lyase results from a post-translational modification of
      PelI occurring extracellularly both in culture media and in planta. This
      modification consists of the cleavage of 97 N-terminal amino acids by the
      extracellular proteases of E. chrysanthemi. The enzymatic properties of the
      maturated form, PelI-3, are not, or only weakly, modified. However, this
      maturation gives rise to a small size and basic form that is active as a defence
      elicitor in plants.

PMID- 9781883
TI  - The identification of exported proteins with gene fusions to invasin.
AB  - Exported proteins are integral to understanding the biology of bacterial
      organisms. They have special significance in pathogenesis research because they
      can mediate critical interactions between pathogens and eukaryotic cell surfaces.
      Further, they frequently serve as targets for vaccines and diagnostic tests. The
      commonly used genetic assays for identifying exported proteins use fusions to
      alkaline phosphatase or beta-lactamase. These systems are not ideal for
      identifying outer membrane proteins because they identify a large number of inner
      membrane proteins as well. We addressed this problem by developing a gene fusion
      system that preferentially identifies proteins that contain cleavable signal
      sequences and are released from the inner membrane. This system selects fusions
      that restore outer membrane localization to an amino terminal-truncated Yersinia
      pseudotuberculosis invasin derivative. In the present study, a variety of
      Salmonella typhimurium proteins that localize beyond the inner membrane were
      identified with gene fusions to this invasin derivative. Previously undescribed
      proteins identified include ones that share homology with components of fimbrial
      operons, multiple drug resistance efflux pumps and a haemolysin. All of the
      positive clones analysed contain cleavable signal sequences. Moreover, over 40%
      of the genes identified encode putative outer membrane proteins. This system has
      several features that may make it especially useful in the study of genetically
      intractable organisms.

PMID- 9781885
TI  - Vibrio cholerae iron transport: haem transport genes are linked to one of two
      sets of tonB, exbB, exbD genes.
AB  - Vibrio cholerae was found to have two sets of genes encoding TonB, ExbB and ExbD
      proteins. The first set (tonB1, exbB1, exbD1) was obtained by complementation of
      a V. cholerae tonB mutant. In the mutant, a plasmid containing these genes
      permitted transport via the known V. cholerae high-affinity iron transport
      systems, including uptake of haem, vibriobactin and ferrichrome. When chromosomal
      mutations in exbB1 or exbD1 were introduced into a wild-type V. cholerae
      background, no defect in iron transport was noted, indicating the existence of
      additional genes that can complement the defect in the wild-type background.
      Another region of the V. cholerae chromosome was cloned that encoded a second
      functional TonB/Exb system (tonB2, exbB2, exbD2). A chromosomal mutation in exbB2
      also failed to exhibit a defect in iron transport, but a V. cholerae strain that
      had chromosomal mutations in both the exbB1 and exbB2 genes displayed a mutant
      phenotype similar to that of an Escherichia coli tonB mutant. The genes encoding
      TonB1, ExbB1, ExbD1 were part of an operon that included three haem transport
      genes (hutBCD), and all six genes appeared to be expressed from a single Fur
      regulated promoter upstream of tonB1. A plasmid containing all six genes
      permitted utilization of haem by an E. coli strain expressing the V. cholerae
      haem receptor, HutA. Analysis of the hut genes indicated that hutBCD, which are
      predicted to encode a periplasmic binding protein (HutB) and cytoplasmic membrane
      permease (HutC and HutD), were required to reconstitute the V. cholerae haem
      transport system in E. coli. In V. cholerae, the presence of hutBCD stimulated
      growth when haemin was the iron source, but these genes were not essential for
      haemin utilization in V. cholerae.

PMID- 9781884
TI  - Identification of the Vibrio cholerae type 4 prepilin peptidase required for
      cholera toxin secretion and pilus formation.
AB  - Cholera toxin secretion is dependent upon the extracellular protein secretion
      apparatus encoded by the eps gene locus of Vibrio cholerae. Although the eps gene
      locus encodes several type four prepilin-like proteins, the peptidase responsible
      for processing these proteins has not been identified. This report describes the
      identification of a prepilin peptidase from the V. cholerae genomic database by
      virtue of its homology with the PilD prepilin peptidase of Pseudomonas
      aeruginosa. Plasmid disruption or deletion of this peptidase gene in either EI
      Tor or classical V. cholerae O1 biotype strains results in a dramatic decrease in
      cholera toxin secretion. In the case of the EI Tor biotype mutants, surface
      expression of the type 4 pilus responsible for mannose-sensitive
      haemagglutination is abolished. The cloned V. cholerae peptidase processes either
      EpsI or MshA preproteins when co-expressed in E. coli. Mutation of the V.
      cholerae peptidase gene also results in a defect in virulence and decreased
      levels of OmpU. The V. cholerae peptidase gene sequence shows 80% homology with
      the Vibrio vulnificus VvpD type 4 prepilin peptidase required for pilus assembly
      and cytolysin secretion in V. vulnificus. Accordingly, the V. cholerae type 4
      prepilin peptidase required for pilus assembly and cholera toxin secretion has
      been designated VcpD.

PMID- 9781886
TI  - A global repressor (Mlc) is involved in glucose induction of the ptsG gene
      encoding major glucose transporter in Escherichia coli.
AB  - Glucose stimulates the expression of ptsG encoding the major glucose transporter
      in Escherichia coli. We isolated Tn 10 insertion mutations that confer
      constitutive expression of ptsG. The mutated gene was identified as mlc, encoding
      a protein that is known to be a repressor for transcription of several genes
      involved in carbohydrate utilization. Expression of ptsG was eliminated in a mlc
      crp double-negative mutant. The Mlc protein was overproduced and purified. In
      vitro transcription studies demonstrated that transcription of ptsG is stimulated
      by CRP-cAMP and repressed by Mlc. The action of Mlc is dominant over that of CRP
      cAMP. DNase I footprinting experiments revealed that CRP-cAMP binds at two sites
      centred at -40.5 and -95.5 and that Mlc binds at two regions centred around -8
      and -175. The binding of CRP-cAMP stimulated the binding of RNA polymerase to the
      promoter while Mlc inhibited the binding of RNA polymerase but not the binding of
      CRP-cAMP. Gel-mobility shift assay indicated that glucose does not affect the Mlc
      binding to the ptsG promoter. Our results suggest that Mlc is responsible for the
      repression of ptsG transcription and that glucose modulates the Mlc activity by
      unknown mechanism.

PMID- 9781888
TI  - Correlation of PAS domains with electron transport-associated proteins in
      completely sequenced microbial genomes.

PMID- 9781887
TI  - Does antizyme exist in Escherichia coli?

PMID- 9781889
TI  - Is there a relic of a spliceosomal intron in Bacillus subtilis temperate phage
      SPbeta?

PMID- 9781891
TI  - Plate osteosynthesis of the distal femur: surgical techniques and results.
AB  - Over the past three decades, the techniques for internal fixation of the distal
      femur have evolved to provide reliably successful results. The improved outcomes
      of plate osteosynthesis of distal femur fractures are because of better implants,
      techniques of anatomic reduction and soft tissue handling, and post-fixation
      stability with early motion. We review the traditional Arbeitsgemeinschaft fur
      Osteosynthesefragen (AO) surgical techniques for plate osteosynthesis of the
      distal femur and the results reported using these methods.

PMID- 9781890
TI  - Mutations in the cmaB gene are responsible for the absence of methoxymycolic acid
      in Mycobacterium bovis BCG Pasteur.

PMID- 9781892
TI  - Cementless total hip replacement in patients with developmental dysplasia of the
      hip.
AB  - This study was conducted to evaluate the clinical and radiographic results of 22
      total hip replacements done in 17 consecutive patients for coxarthrosis due to
      developmental dysplasia or dislocation of the hip. All operations were done using
      an anterior approach without trochanteric osteotomy. Standard cementless
      prostheses were used in all cases. There was no custom-designed prosthesis used.
      The acetabular cup was placed in an anatomic position in the true acetabulum in
      every case. Bulk autograft was necessary to reconstruct the deficient acetabular
      roof in only 2 hips. The average follow-up was 63 months (range, 40 months to 95
      months). The average Harris Hip Score was improved from a preoperative value of
      35 (range, 24 to 46), to 96 (range, 79 to 100) at final follow-up. To date, no
      revision has been done. Three hips showed radiographic evidence suggestive of
      aseptic loosening (2 stems and 1 cup), but the clinical results remain
      satisfactory. There is no incidence of dislocation, sciatic nerve palsy, or
      infection.

PMID- 9781893
TI  - Modification of the Bankart reconstruction using a suture anchor.
AB  - A prospective study was done to determine the effectiveness of a suture anchor in
      doing a Modified Bankart Reconstruction on the traumatic unidirectional Bankart
      lesion shoulder. From 1989 to 1991, 26 patients encompassing 27 shoulders with
      recurrent instability had modified Bankart reconstructions. A minimum 18-month
      follow-up was obtained by examination of 24 patients with telephone interviews
      done on two patients. The average follow-up was 23.6 months. A 93.1% good-to
      excellent result was obtained using the Bankart rating scale. There were no
      failures or complications. The surgeon involved in the study thought the suture
      anchor facilitated the attachment of the avulsed capsulolabral complex in doing
      the Bankart procedure.

PMID- 9781894
TI  - Lateral ankle instability correction by translocation of the intact peroneus
      brevis tendon: a prospective study of 45 cases.
AB  - Between November 1982 and November 1991, 45 patients were treated with a new
      procedure for lateral ankle instability and were available for follow-up.
      Preoperatively, all patients had a talar tilt of 10 degrees or more and a
      positive drawer sign. A 9-year follow-up has proven successful in all 45
      patients. All patients had increased postoperative stability and returned to
      their preoperative activities; 70% increased their activities beyond their
      preoperative level. The rehabilitation time has been shortened by 50%.

PMID- 9781895
TI  - Significance of cold intolerance in upper extremity disorders.
AB  - After upper extremity injury, pain on exposure to cold (cold sensitivity) is a
      significant problem. This cross-sectional observational study (1) assesses the
      incidence and prevalence of cold intolerance, (2) evaluates the relationship
      between functional status and degree of cold intolerance, and (3) correlates
      health-related quality of life (HRQL) with symptoms of cold intolerance. Patients
      in a tertiary care center completed questionnaires to document (1) cold
      sensitivity, (2) upper extremity pain, symptoms, and function, and (3) HRQL. Cold
      sensitivity was found to be associated with more functional limitations, greater
      pain, and reduced HRQL. As the severity of cold intolerance increased, functional
      limitations and pain increased and HRQL decreased. Cold intolerance has a
      profound effect on HRQL.

PMID- 9781896
TI  - Effect of standard total knee arthroplasty surgical dissection on human patellar
      blood flow in vivo: an investigation using laser Doppler flowmetry.
AB  - We examined the in vivo alterations of human patellar bone blood flow that occur
      with surgical dissection of the extensor mechanism during total knee
      arthroplasty. A laser doppler probe was used to measure central patellar blood
      flow at baseline after quadriceps tenotomy, after partial fat pad excision, after
      lateral release, and after completion of the lateral release with superolateral
      geniculate sacrifice. The initial quadriceps tenotomy and medial arthrotomy
      decreased patellar vascularity to 60.4% of baseline. Fat pad resection initiated
      another 10.4% decline. The lateral release resulted in a patellar vascularity
      that was 43.6% of baseline. Finally, the loss of superolateral geniculate inflow
      reduced the patellar flow to 30.61% of baseline.

PMID- 9781898
TI  - Prophylactic antibiotics for spine surgery: description of a regimen and its
      rationale.
AB  - Cefazolin, an antibiotic commonly used for surgical prophylaxis, may not
      adequately penetrate the intervertebral disk or cerebrospinal fluid. The
      combination of gentamicin and cefuroxime has been found to penetrate both
      structures in adequate levels and was used in 40 consecutive elective spine cases
      without a postoperative infection or antibiotic-related complications.

PMID- 9781897
TI  - Long-term complications of snake bites to the upper extremity.
AB  - The purpose of this study was to determine long-term complications of upper
      extremity snake envenomations. The records of 73 patients, who were seen for
      snake bites were obtained; 46 of these patients had bites to the upper extremity,
      and 27 had bites to the lower extremity. These patients were graded according to
      the severity of the bite. The snakes involved were eastern diamondback
      rattlesnake, coral snake, pigmy rattlesnake, water moccasin, and unknown.
      Fourteen of the 46 patients receiving upper extremity bites were examined by a
      hand surgeon and an occupational hand therapist 1 to 3.2 years after their bite.
      Subjective pain data, range-of-motion, intrinsic, extrinsic, finger-flexion
      tightness, grip strength, pinch strength and objective sensory data were
      collected. Four patients had continued pain and tissue atrophy at the bite site.
      There were no long-term sequelae from a missed compartment syndrome.

PMID- 9781900
TI  - Natural history of avascular necrosis of the patella due to closed global
      patellar dislocation.
AB  - This 20-year study of avascular necrosis of the patella indicates that the
      patella can regain its blood supply and normal joint surface over time.
      Significant changes in the patella and operative treatment are noted.

PMID- 9781899
TI  - Adolescent tibia vara, nonossifying fibroma, and bipartite patella in a
      nationally ranked adolescent karate competitor.
AB  - I describe a case of adolescent tibia vara, a contralateral nonossifying fibroma
      of the tibia, and bipartite patella, which occurred in an adolescent karate
      competitor of normal stature. The association of this unusual triad supports the
      hypothesis that each process has a shared traumatic etiology.

PMID- 9781901
TI  - Perspectives on overgrowth syndromes.
AB  - In this overview, topics addressed include cellular overgrowth; recent molecular
      advances; problems of "lumping" and "splitting"; classification systems;
      relationship of neoplasia to overgrowth syndromes; vascular malformations; and
      problems in designation of overgrowth syndromes.

PMID- 9781902
TI  - Vignettes from the history of overgrowth and related syndromes.
AB  - Vignettes of several stages in the evolution of present concepts of overgrowth
      and related syndromes are presented. The scientific study of this topic did not
      begin until the 18th century because of its delayed emergence from superstition
      and fallacy. Examples of early superstitions concerning gigantism are presented,
      with some historical comments on infant giants. The pioneering contributions of
      Isodore Geoffroy Saint-Hilaire to the scientific analysis of overgrowth are
      emphasized. Details concerning the early history of the growth syndrome
      associated with the names of Wiedemann and Beckwith is presented, with emphasis
      on cases reported prior to ours.

PMID- 9781903
TI  - Correlates of prenatal visceromegaly.
AB  - Aside from recognized overgrowth syndromes, instances of visceromegaly are not
      uncommon at perinatal autopsy. The database of the University of Michigan
      Teratology Unit was screened for individual viscera exceeding the 90th centile
      for body and brain weight standards. The data were stratified for several
      maternal (hypertension, diabetes, obesity), gestational (chorioamnionitis,
      oligohydramnios, amniorrhaea, polyhydramnios), and fetal (body wall defect,
      cardiac malformation, renal malformation, diaphragmatic hernia, nonimmune
      hydrops, twin transfusion syndrome) characteristics and tested for statistically
      significant excessive numbers of heavy organs. The most striking associations
      were heavy adrenal glands and liver with chorioamnionitis, heavy heart with
      polyhydramnios and in the twin transfusion syndrome, and heavy heart and liver
      with nonimmune hydrops. Excessive brain weight for body weight had a number of
      correlations, each most likely reflecting growth restriction with sparing of
      brain growth.

PMID- 9781904
TI  - Molecular genetics of Wiedemann-Beckwith syndrome.
AB  - Wiedemann-Beckwith syndrome (WBS) is a heterogeneous overgrowth syndrome
      associated with malformations and an elevated risk of developing embryonal
      tumors. WBS is a multigenic disorder caused by dysregulation of imprinted growth
      regulatory genes within the 11p15 region. Elucidation of the genetic cause of WBS
      will provide important insights into the molecular and epigenetic changes
      associated with loss of normal growth control and cancer in this syndrome.
      Currently available protocols for diagnostic testing, patient monitoring and
      genetic counselling will evolve as our understanding of the molecular basis of
      WBS progresses.

PMID- 9781905
TI  - Wilms tumor genetics.
AB  - Wilms tumor (WT), a sporadic and familial childhood kidney tumor, is genetically
      heterogeneous. One WT gene, WT1 at 11p13, has been cloned, but only a minority of
      WTs carry detectable mutations at that locus. WT1 can also be excluded as the
      predisposition gene in most WT families, implying the existence of other WT
      genes. Studies of WT families have demonstrated that familial predisposition is
      also heterogeneous and involves at least two other loci besides WT1. In addition
      to WT1 and the familial predisposition genes, a role for other genes in the
      development of WTs is implied by the somatic occurrence of genetic and epigenetic
      alterations such as loss of heterozygosity and loss of imprinting in tumors and,
      rarely, the observation of nonchromosome-11 constitutional aberrations in WT
      patients. Determining the pattern of presence or absence of these various genetic
      alterations in tumors and elucidating the function of the genes involved will
      provide a better understanding of the cellular processes that are critical for
      normal cell growth and differentiation, but are abrogated in the course of
      tumorigenesis.

PMID- 9781906
TI  - Nephrogenic rests and the pathogenesis of Wilms tumor: developmental and clinical
      considerations.
AB  - Nephrogenic rests (NR) are abnormally persistent clusters of embryonal cells,
      representing microscopic malformations (dysplasias) of the developing kidney.
      Though NR are best known as precursors of Wilms tumor (WT), many alternative
      fates are observed, and most rests are destined for eventual atresia. Biological
      and clinical distinctions between the two major NR categories, perilobar and
      intralobar rests (PLNR and ILNR) are emphasized. PLNR occur in fetal overgrowth
      and with certain overgrowth syndromes. ILNR are frequently associated with
      deletions or mutations of WT1. Data are presented concerning the prevalence of NR
      in general pediatric autopsy populations, and in selected syndromes. The age at
      diagnosis of WT was determined for the largest series of patients with WT
      associated syndromes reported to date. These data provide a basis for determining
      how long patients with these conditions are at risk for WT development.

PMID- 9781907
TI  - Isolated hemihyperplasia (hemihypertrophy): report of a prospective multicenter
      study of the incidence of neoplasia and review.
AB  - Hemihyperplasia is characterized by asymmetric growth of cranium, face, trunk,
      limbs, and/or digits, with or without visceral involvement. It may be an isolated
      finding in an otherwise normal individual, or it may occur in several syndromes.
      Although isolated hemihyperplasia (IHH) is of unknown cause, it may represent one
      end of the clinical spectrum of the Wiedemann-Beckwith syndrome (WBS).
      Uniparental paternal disomy of 11p15.5 or altered expression of insulin-like
      growth factor 2 (IGF2) from the normally silent maternal allele have been
      implicated as causes of some cases of WBS. IHH and other mild manifestations of
      WBS may represent patchy overexpression of the IGF2 gene following defective
      imprinting in a mosaic fashion. The natural history of IHH varies markedly. An
      association among many overgrowth syndromes and a predisposition to neoplasia is
      well recognized. Heretofore the risk for tumor development in children with IHH
      was unknown. We report on the results of a prospective multicenter clinical study
      of the incidence and nature of neoplasia in children evaluated because of IHH.
      One hundred sixty-eight patients were ascertained. A total of 10 tumors developed
      in nine patients, for an overall incidence of 5.9%. Tumors were of embryonal
      origin (similar to those noted in other overgrowth disorders), including Wilms
      tumor, hepatoblastoma, adrenal cell carcinoma, and leiomyosarcoma of the small
      bowel in one case. These data support a tumor surveillance protocol for children
      with IHH similar to that performed in other syndromes associated with overgrowth.

PMID- 9781908
TI  - Clinical and molecular aspects of the Simpson-Golabi-Behmel syndrome.
AB  - The Simpson-Golabi-Behmel syndrome (SGBS) is an overgrowth/multiple congenital
      anomalies/dysplasia syndrome caused by a mutant X-linked gene. The spectrum of
      its clinical manifestations is broad, varying from very mild forms in carrier
      females to infantile lethal forms in affected males. A typically affected male
      will show tall stature, "coarse" face, supernumerary nipples, congenital heart
      defect, and generalized muscular hypotonia. Mental development is normal in most
      cases. There is an increased risk of neoplasia in infancy, especially Wilms
      tumor. The SGBS gene spans 500 kilobases in the Xq26 region and contains eight
      exons. It encodes an extracellular proteoglycan, designated glypican 3 (GPC3),
      capable of interacting with the insulin-like growth factor IGF2. At present, only
      deletions of various sizes have been found in a number of affected families.

PMID- 9781909
TI  - Inherited macrocephaly-hamartoma syndromes.
AB  - Recent discoveries in the molecular biology of the phosphatase and tensin homolog
      (PTEN) locus in the q22-23 region of chromosome 10 prove and/or suggest that
      several syndromes previously considered to be clinically and genetically distinct
      entities should actually be unified into a single entity. This conclusion is most
      secure for the Cowden and "Bannayan-Zonana" phenotypes, but almost certainly
      should also include the "Riley-Ruvalcaba" and Lhermitte-Duclos phenotypes as well
      benign familial macrocephaly and external hydrocephalus. The clinical and
      molecular data supporting this unification are presented along with a proposal
      for new nomenclature-the PTEN MATCHS (macrocephaly, autosomal dominant, thyroid
      disease, cancer, hamartomata, skin abnormalities) syndrome-based on the observed
      clinical abnormalities.

PMID- 9781910
TI  - Nonsyndromal overgrowth in males with mild psychomotor delay.
AB  - Over the last 3 years we ascertained 42 patients for statural overgrowth and/or
      macrocephaly, who also had mild developmental delay. There were 39 males and
      three females, two of whom were sisters. In no case was tall stature a familial
      characteristic. Family history was unremarkable, except for the case of the two
      sisters. Physical examination did not demonstrate any consistent pattern of
      malformations or anomalies identifying a syndrome, known or unknown. Chromosomes
      were apparently normal and the molecular test for the fragile X syndrome yielded
      normal results in all cases. Muscular hypotonia, advanced bone age, and epilepsy
      were relatively consistent manifestations. The hypothalamus-pituitary axis seemed
      to be intact when tested through the blood levels of insulin-like growth factors
      I and II and of the insulin-like growth binding protein 3, and the excess of
      growth was apparently growth hormone independent. The condition comprising
      excessive growth, developmental delay, muscular hypotonia, absence of a
      consistent pattern of physical anomalies, and apparently sporadic occurrence,
      largely limited to males, may be heterogenous.

PMID- 9781911
TI  - The syndromes of Sotos and Weaver: reports and review.
AB  - The syndromes of Sotos and Weaver are paradigmatic of the daily nosologic
      difficulties faced by clinical geneticists attempting to diagnose and counsel,
      and to give accurate prognoses in cases of extensive phenotypic overlap between
      molecularly undefined entities. Vertebrate development is constrained into only
      very few final or common developmental paths; therefore, no developmental anomaly
      seen in humans is unique to ("pathognomonic" of) one syndrome. Thus, it is not
      surprising that prenatal overgrowth occurs in several syndromes, including the
      Sotos and Weaver syndromes. Are they sufficiently different in other respects to
      allow the postulation of locus (rather than allele) heterogeneity? Phenotypic
      data in both conditions are biased because of ascertainment of propositi, and the
      apparent differences between them may be entirely artificial as they were between
      the G and BBB syndromes. On the other hand, the Sotos syndrome may be a cancer
      syndrome, the Weaver syndrome not (though a neuroblastoma was reported in the
      latter); in the former there is also remarkably advanced dental maturation rarely
      commented on in the latter. In Weaver syndrome there are more conspicuous
      contractures and a facial appearance that experts find convincingly different
      from that of Sotos individuals. Nevertheless, the hypothesis of locus
      heterogeneity is testable; at the moment we are inclined to favor the hypothesis
      of allele heterogeneity. An international effort is required to map, isolate, and
      sequence the causal gene or genes.

PMID- 9781912
TI  - Weaver syndrome: autosomal dominant inheritance of the disorder.
AB  - Weaver syndrome (WS), a condition first described in 1974 by Weaver et al.,
      consists of macrosomia, advanced skeletal age, characteristic pattern of facial
      and radiographic anomalies, and contractures. Although there have been three
      reports of close relatives (sibs or both parent and offspring) affected with this
      condition, the syndrome generally occurs sporadically, and the recurrence risk in
      sporadic cases appears to be low. We report here on a family in which the
      propositus and his sister were born with the facial phenotype, club feet, and
      macrosomia characteristic of WS. Their father had macrosomia and macrocephaly as
      an adult, and childhood photos show clearly that he has WS. Two sisters of the
      propositus have had normal growth and development. The syndrome in this family
      appears to be inherited in an autosomal dominant fashion.

PMID- 9781913
TI  - Clinical differentiation between Proteus syndrome and hemihyperplasia:
      description of a distinct form of hemihyperplasia.
AB  - Proteus syndrome is a rare and highly variable hamartomatous syndrome that can
      affect multiple organ systems. It is characterized by hyperplastic lesions of
      connective tissue, vascular malformations, linear verrucous epidermal nevi, and
      hyperostoses. The cause of the disorder is unknown, but the current working
      hypothesis is that it is caused by a mosaic alteration that leads to a highly
      variable phenotype, equal sex ratio, sporadic occurrence, and discordant
      monozygotic twins. Herein we describe our experience with 18 patients with a
      referring diagnosis of Proteus syndrome. It was found that imaging studies are
      very useful for the characterization of the syndrome. One finding was that
      splenic hyperplasia can be a manifestation of Proteus syndrome. Analysis of the
      clinical data shows that Proteus syndrome is frequently confused with
      "hemihyperplasia." A distinct subtype of hemihyperplasia is defined that includes
      static or mildly progressive hemihyperplasia and multiple lipomata.

PMID- 9781915
TI  - Congenital heart defects in Sotos syndrome.
AB  - Sotos syndrome is a relatively common overgrowth syndrome with characteristic
      physiognomy. We report on 3 patients with congenital heart defects out of 14
      Sotos syndrome patients studied clinically and or by echocardiography. Review
      showed another 17 patients with variable cardiac defects, mostly closure defects,
      making an overall incidence of approximately 8%.

PMID- 9781914
TI  - Klippel-Trenaunay syndrome.
AB  - Patients with Klippel-Trenaunay (KT) syndrome have a complex constellation of
      anomalies that includes cutaneous capillary malformation (usually on an affected
      limb), abnormal development of the deep and superficial veins, and limb
      asymmetry, usually enlargement. Mixed vascular malformations may be present and
      include capillary, venous, arterial, and lymphatic systems. The records of 79
      patients referred for vascular anomalies were reviewed and 49 were found to have
      the three "cardinal" anomalies of KT syndrome. Twenty-six females and 23 males
      had 46 affected legs (27 right legs), 23 affected arms (15 right), 21 affected
      trunks, and 10 affected heads. Thirty-six had only one affected quadrant, 8 had
      two, and 5 had three or more. Although 40 patients had increased limb girth,
      measurable length discrepancy was noted in only 17 individuals. Patients were
      evaluated using a noninvasive imaging strategy including color duplex
      ultrasonography, MRI, lymphoscintigraphy, and plain radiographs. Treatment
      included compression, pulsed-dye laser treatment, reduction of arteriovenous
      malformations, and orthopedic procedures for overgrowth. All KT cases in this
      series occurred sporadically. We speculate that KT syndromes may be due to a
      somatic mutation for a factor critical to vasculogenesis and angiogenesis in
      embryonic development.

PMID- 9781916
TI  - Identical twins discordant for Sotos syndrome.
AB  - The cause of Sotos syndrome is unknown but it usually occurs sporadically. Recent
      studies have shown no evidence of uniparental disomy. One set of concordant
      monozygotic twins has been reported. We have identified the Sotos syndrome in one
      of two 5-year-old male monozygotic twins. Our finding of discordance in these
      identical twins suggests that a postconceptual mutation, or epigenetic change
      and/or an environmental factor may be involved in the cause of Sotos syndrome.

PMID- 9781917
TI  - Endothelium-dependent vascular effects of Pycnogenol.
AB  - Pycnogenol (P) is purported to exhibit effects that could be beneficial in terms
      of prevention of chronic age-related diseases such as atherosclerosis. The most
      studied of these effects is its antioxidant/free radical-scavenging activity. In
      this study, we investigated the possibility that this supplement might produce
      vascular effects by stimulation of nitric oxide (NO) production by vascular
      endothelial cells. In the in vitro experiments, P (1-10 microg/ml) relaxed
      epinephrine (E)-, norepinephrine (NE)-, and phenylephrine (PE)-contracted intact
      rat aortic ring preparations in a concentration-dependent manner. However, when
      the endothelial lining of the aortic ring was removed, P had no effect,
      indicating an endothelium-dependent relaxing (EDR) effect. This EDR response was
      caused by enhanced NO levels, because the NO synthase (NOS) inhibitor N-methyl-L
      arginine (NMA) reversed (or prevented) the relaxation, and this response, in
      turn, was reversed by addition of L-arginine, the normal substrate for NOS.
      Pycnogenol-induced EDR persisted after exposure of intact rings to high levels of
      superoxide dismutase (SOD), suggesting that the mechanism of EDR did not involve
      scavenging of superoxide anion. In addition to causing relaxation, preincubation
      of aortic rings with P (1-10 microg/ml) inhibited subsequent E- and NE-induced
      contractions in a concentration-dependent manner. Fractionation of P by Sephadex
      LH-20 chromatography resulted in three fractions, one of which (fraction 3,
      oligomeric procyanidins) exhibited potent EDR activity. These results indicate
      that P, in addition to its antioxidant activity, stimulates constitutive
      endothelial NOS (eNOS) activity to increase NO levels, which could counteract the
      vasoconstrictor effects of E and NE. Furthermore, additional protective effects
      could result from the well-established properties of NO to decrease platelet
      aggregation and adhesion, as well as to inhibit low-density lipoprotein (LDL)
      cholesterol oxidation, all of which could protect against atherogenesis and
      thrombus formation.

PMID- 9781918
TI  - A double-blind placebo-controlled evaluation of the human electrophysiologic
      effects of zatebradine, a sinus node inhibitor.
AB  - The purpose of this study was to evaluate the electrophysiologic effects of
      zatebradine, a sinus node inhibitor, in human subjects. Patients without
      structural heart disease were randomized to receive intravenous zatebradine (23
      patients) or placebo (12 patients). Electrophysiologic measures were obtained at
      baseline and repeated at 40 and 70 min after drug administration. In the placebo
      group, there were no significant changes in any parameter over time. After
      zatebradine, sinus node function changed significantly at 40 min, with no further
      change at 70 min; sinus cycle length was prolonged by 16 and 17% (p < 0.001), and
      corrected sinus node recovery time was prolonged by 30 and 22% (p = 0.008).
      Similarly, atrioventricular node function changed significantly at 40 min, with
      no further change at 70 min; atrio-His interval was prolonged by 15 and 15% (p =
      0.02), atrioventricular node effective refractory period was prolonged by 12 and
      11% (p = 0.01), and Wenckebach cycle length was prolonged by 15 and 11% (p =
      0.002). Atrial refractoriness, His-Purkinje conduction, ventricular
      refractoriness, and action-potential duration were not affected by zatebradine.
      Zatebradine, a sinus node inhibitor, alters the conduction and refractory
      properties of the human atrioventricular node, in addition to the expected effect
      on sinus node function.

PMID- 9781919
TI  - Disopyramide, imipramine, and amitriptyline bind to a common site on the
      transient outward K+ channel.
AB  - Previous work demonstrated that several antiarrhythmic agents and antidepressive
      drugs block transient outward K+ current (I(to)) in rat ventricular myocytes. The
      antiarrhythmic drug, disopyramide, and the tricyclic antidepressants, imipramine
      and amitriptyline, block the I(to) channel mainly when it is in the open state.
      The rate of recovery from block induced by disopyramide is so slow that the drug
      produces a use-dependent block at 1 Hz, whereas the rate of recovery from block
      in the presence of imipramine and amitriptyline is fast enough so as not to
      induce any use-dependent block at this frequency. We studied the effects of the
      combinations of disopyramide-imipramine and disopyramide-amitriptyline on I(to)
      to detect possible interactions between the drugs on I(to) blockade. The effects
      of imipramine and amitriptyline on the use-dependent effect induced by
      disopyramide and on the rate of recovery of the channels blocked by this drug
      allow us to conclude that there is only one common receptor site in the channel
      molecule for the three drug molecules.

PMID- 9781920
TI  - Mechanism of block of cardiac transient outward K+ current (I(to)) by
      antidepressant drugs.
AB  - Imipramine, amitriptyline, mianserine, maprotiline, and trazodone are five widely
      used antidepressant drugs with different chemical structures. Imipramine and
      amitriptyline are tricyclics, mianserine and maprotiline are tetracyclics, and
      trazodone is a triazolopyridine derivative. We studied the effects of these drugs
      on the transient outward K+ current (I(to)) and the interaction mechanisms within
      the drug molecules and the channel-binding site. The transient outward K+ current
      is mainly responsible for action-potential repolarization in the rat ventricle,
      and all of the five drugs studied block I(to), but in different manners. Cyclic
      drugs block I(to) in the open state of the channel with very little block in the
      rested or inactivated states or both. Trazodone blocks the channel in a state
      independent manner. From these results, we suggest that a relation exists between
      drug structure and preference for the different channel conformations.

PMID- 9781921
TI  - Beta-adrenergic stimulation of reperfused myocardium after 2-hour ischemia.
AB  - Postischemic myocardium possesses considerable contractile and metabolic
      reserves, but their mobilization could result in increased cell death. We tested
      the hypothesis that beta-adrenergic stimulation of reperfused myocardium would
      increase segment work more than O2 consumption, thereby improving efficiency
      without increased cell death. In 16 open-chest anesthetized dogs, the left
      anterior descending coronary artery (LAD) was ligated for 2 h; during the
      reperfusion period, isoproterenol (ISO; 0.1 microg/kg/min, i.v.) was administered
      to nine of the animals. Regional myocardial segment length and force were
      measured in the anterior (LAD) and posterior circumflex coronary artery (CFX)
      regions of the left ventricular myocardium. Work was calculated as the integrated
      products of force and shortening for each region. Regional myocardial O2
      consumption was obtained from LAD flow and arterial and local venous O2
      saturations. Infarct size (tetrazolium) was measured in the treated and untreated
      hearts at the end of the experiment. In untreated hearts, the first derivative of
      left ventricular pressure, cardiac output, and external work were significantly
      depressed during reperfusion; ISO restored all values to preocclusion levels.
      Regional myocardial work in both LAD and CFX regions was significantly increased
      by ISO (from 564 +/- 207 to 1,635 +/- 543 g/mm/min in LAD, and from 753 +/- 90 to
      1,426 +/- 245 g/mm/min in CFX). Efficiency (work/oxygen consumption) of the
      reperfused region was similarly increased. LAD flow was significantly increased
      by ISO, and O2 extraction was unchanged. Infarct size was 28.2 +/- 4.7% in
      untreated hearts and 29.0 +/- 3.5% in ISO hearts. Thus isoproterenol stimulation
      significantly improved both regional and global function without subsequent
      evidence of increased cell death.

PMID- 9781922
TI  - Modulation of cAMP-mediated vasorelaxation by endothelial nitric oxide and basal
      cGMP in vascular smooth muscle.
AB  - Recent in vitro evidence shows a role of endothelial nitric oxide (NO) in the
      modulation of isoproterenol-induced vasorelaxation. To elucidate roles of
      endothelial cells and NO in cyclic adenosine monophosphate (cAMP)-mediated
      vasodilators we examined the effects of removal of endothelium and a NO synthase
      (NOS) inhibitor on relaxant responses in vitro of rat aortic strips to beta
      adrenoceptor stimulants and colforsin dapropate, a water-soluble forskolin, and
      changes in cAMP and cyclic guanosine monophosphate (cGMP) contents. Relaxant
      responses of rat aorta to isoproterenol, denopamine, salbutamol, colforsin, and
      dibutyryl cAMP (dbcAMP) were blunted by removal of endothelial cells or treatment
      with NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). Relaxant response
      of endothelium-intact segments to isoproterenol was associated with increases in
      tissue cAMP and cGMP contents. Removal of endothelium or treatment with L-NAME
      markedly reduced basal cGMP and abolished the isoproterenol-induced increase in
      cGMP but not cAMP content. In endothelium-removed segments, pretreatment with
      sodium nitroprusside (SNP) restored the diminished relaxant response to
      isoproterenol and increased basal cGMP (from 0.08 +/- 0.01 to 0.16 +/- 0.02
      pmol/mg protein), whereas it did not affect the isoproterenol-induced increase in
      cAMP. The diminished relaxant response of endothelium-removed segments to dbcAMP
      was not restored by SNP pretreatment. The results suggest that relaxant response
      of rat aorta to cAMP-mediated vasodilators is mediated, in part, by NO production
      in endothelium and subsequent increase in cGMP in vascular smooth-muscle cells.

PMID- 9781923
TI  - Acadesine increases blood flow in the collateralized heart during exercise.
AB  - Acadesine, an adenosine-regulating agent, has been shown to increase coronary
      flow and exert cardioprotective effects in acutely ischemic myocardium, but a
      beneficial effect on coronary collateral flow during exercise has not been
      demonstrated. We examined the effect of acadesine, 100 micromol/min, i.v., on
      myocardial blood flow during treadmill exercise in six normal dogs and seven dogs
      with moderately well-developed coronary collateral vessels. Collateral vessel
      growth was produced with 2-min intermittent occlusions of the left circumflex
      coronary artery followed by permanent occlusion. During resting conditions,
      myocardial blood flow in the collateral zone was not significantly less than in
      the normal zone, but during exercise, blood flow increased by only 79 +/- 21%
      (from 0.98 +/- 0.29 ml/min/g to 1.64 +/- 0.19 ml/min/g; p < 0.05) in the
      collateral zone as compared with 118 +/- 32% (from 1.09 +/- 0.28 ml/min/g to 2.14
      +/- 0.2 ml/min/g; p < 0.01) in the normal zone. During exercise, acadesine
      further increased mean blood flow in the collateral-dependent region by 24 +/- 5%
      (to 2.04 +/- 0.26 ml/min/g; p < 0.05) with no change in the transmural
      distribution of perfusion. The increase in collateral zone blood flow in response
      to acadesine resulted from a decrease in both transcollateral resistance from
      25.1 +/- 2.7 mm Hg/min/g/ml to 18.8 +/- 8 mm Hg/min/g/ml (p < 0.05) and small
      vessel resistance in the collateral-dependent myocardium from 45.3 +/- 6.6 mm
      Hg/min/g/ml to 36.4 +/- 5.8 mm Hg/min/g/ml (p < 0.05). Acadesine also
      significantly increased normal-zone flow in the collateralized dogs (to 2.62 +/-
      0.33 ml/min/g; p < 0.05). In contrast, acadesine had no effect on coronary blood
      flow in normal dogs. In dogs with moderately well-developed collateral vessels,
      acadesine increased blood flow in both the collateral-dependent and normal
      myocardial zones during exercise. In contrast, acadesine did not increase blood
      flow in normal dogs. These findings suggest that adenosine metabolism is altered
      not only in the collateral-dependent region but also in the normal region of
      hearts with a coronary artery occlusion.

PMID- 9781924
TI  - Relation between impairment in nitric oxide pathway and clinical status in
      patients with congestive heart failure.
AB  - A dissociation between basal and stimulated release of nitric oxide (NO) has been
      found in the peripheral vasculature of patients with congestive heart failure. To
      explore basal and stimulated NO-mediated vasodilation in patients with heart
      failure of varying severity, three groups of subjects were studied: group 1,
      eight normal subjects; group 2, six patients with moderate heart failure; and
      group 3, eight patients with severe heart failure. Forearm blood flow (FBF) was
      measured by plethysmography in response to local brachial infusion of
      acetylcholine, N(G)-monomethyl-L-arginine (L-NMMA), sodium nitroprusside (SNP),
      and noradrenaline (NA). The vasodilating response to acetylcholine was markedly
      impaired in patients with severe heart failure compared with the other groups,
      with FBF increasing by 59 +/- 19% in group 3 vs. 220 +/- 64% in group 2 (p <
      0.05) and 586 +/- 168% in group 1 (p < 0.01) at 80 microg/min acetylcholine. As
      compared with controls, vasodilation to SNP was impaired in group 3 but unchanged
      in group 2. NA caused similar vasoconstrictor response in the three groups,
      whereas vasoconstriction to L-NMMA was less marked in group 3. These results show
      that vasodilator responses to both acetylcholine and SNP are impaired in patients
      with heart failure and that this impairment is related to the clinical severity
      of heart failure.

PMID- 9781925
TI  - Effects of the vasopressin V1 agonist [Phe2,Ile3,Orn8]] vasopressin on regional
      kidney perfusion and renal excretory function in anesthetized rabbits.
AB  - To test whether renal V1-receptors selectively influence blood flow in the renal
      medulla, we compared the effects of infusion of [Phe2,Ile3,Orn8]vasopressin (3-30
      ng/kg/min) by the intravenous, renal arterial, and renal medullary interstitial
      routes in anesthetized rabbits. Intravenous [Phe2,Ile3,Orn8]vasopressin (30
      ng/kg/min) reduced renal medullary perfusion (MBF) by 36 +/- 5% but did not
      significantly affect cortical perfusion (CBF). MBF was also reduced with the
      renal arterial (35 +/- 5%) and renal medullary interstitial (40 +/- 7%) routes
      but, in contrast to the intravenous infusion, CBF was also reduced, by 21 +/- 3%
      and 15 +/- 3%, respectively. Urine flow and sodium excretion were increased by
      [Phe2,Ile3,Orn8]vasopressin, and with direct intrarenal administration, this
      effect was similar for both the infused (left) and noninfused (right) kidneys.
      After a 20-min renal medullary interstitial infusion of [3H]norepinephrine,
      radiolabel concentration was approximately fivefold greater in the left medulla
      than in the left cortex. We conclude that [Phe2,Ile3,Orn8]vasopressin acts on V1
      receptors to alter regional kidney blood flow and tubular salt and water
      handling. The V1-receptors involved are almost certainly within the kidney
      itself, but given the contrasting effects of the different infusion routes on MBF
      and CBF, we cannot exclude the possibility that some of the observed effects of
      [Phe2,Ile3,Orn8]vasopressin are mediated by activation of extra-renal V1
      receptors.

PMID- 9781927
TI  - Losartan attenuates modest but not strong renal vasoconstriction induced by
      nitric oxide inhibition.
AB  - Previous studies showed variable success of angiotensin II (ANG II) antagonists
      to oppose systemic and renal vasoconstriction during long-term nitric oxide
      synthase (NOS) inhibition. We explored in short-term experiments whether the
      systemic and renal vasodilatory response to angiotensin II type 1 (AT1)-receptor
      blockade depends on the extent of NOS blockade. In the first series of
      experiments, anesthetized rats underwent clearance studies during continuous
      monitoring of mean arterial pressure (MAP), renal blood flow (RBF, flow probe),
      and renal vascular resistance (RVR). Compared with control animals, low-dose
      infusion of the NOS-inhibitor nitro-L-arginine (NLA) increased MAP and RVR,
      decreased glomerular filtration rate, RBF, and sodium excretion, and had no
      effect on plasma and kidney ANG II content. High-dose NLA induced stronger
      effects, did not affect plasma ANG II, and reduced kidney ANG II to approximately
      60%. In the second series of experiments, we studied the effect of low- and high
      dose NLA on autoregulation of RBF. NLA induced a dose-dependent increase in MAP
      and decrease in RBF but left autoregulation intact. The AT1-receptor antagonist
      losartan restored MAP and RBF during low-dose NLA but had no depressor or renal
      vasodilating effect during high-dose NLA. In summary, short-term NOS blockade
      causes a dose-dependent pressor and renal vasoconstrictor response, without
      affecting renal autoregulation, and AT1-receptor blockade restores systemic
      pressor and renal vasoconstrictive effects of mild NOS inhibition but fails to
      exert vasorelaxation during strong NOS blockade. Both levels of NOS inhibition
      did not importantly alter intrarenal ANG II levels. Apparently the functional
      role of endogenous ANG II as determinant of vascular tone is diminished during
      strong NOS inhibition.

PMID- 9781926
TI  - A high concentration of melatonin inhibits in vitro LDL peroxidation but not
      oxidized LDL toxicity toward cultured endothelial cells.
AB  - The pineal hormone, melatonin, was recently found to be a potent free scavenger
      for hydroxyl and peroxyl radicals. Melatonin also inhibits neuronal and thymocyte
      damage due to oxidative stress. Atherosclerosis development is mediated by low
      density lipoprotein (LDL) oxidation and the endocytosis of oxidized LDL by
      resident macrophages in the subendothelial vascular wall. Furthermore, the
      cytotoxic effect of oxidized LDL increases atherogenicity. The goal of this study
      was to compare the antioxidant activities of melatonin and vitamin E against in
      vitro LDL oxidation and their cytoprotective actions against oxidized LDL-induced
      endothelial cell toxicity. An attempt at loading LDL with melatonin by incubating
      human plasma with an ethanolic melatonin solution gave only low protection
      against Cu2+-induced LDL oxidation in comparison with vitamin E and gave no
      detectable incorporation of melatonin into LDL, measured by high-performance
      liquid chromatography (HPLC) coupled to UV detection. High concentrations of
      melatonin (10-100 microM) added to the oxidative medium induced a clear
      inhibition of Cu2+-induced LDL oxidation, characterized as an increase in the lag
      phase duration of conjugated diene formation and decreases in the maximal rate of
      the propagation phase and in the maximal amount of conjugated diene formation.
      Determination of the median efficacious dose (ED50) of melatonin and vitamin E by
      their ability to increase lag-phase duration showed that melatonin was less
      active than vitamin E (ED50, 79 vs. 10 microM, respectively). Melatonin was also
      less active than vitamin E in limiting the formation of thiobarbituric acid
      reactive substances (TBARS) and LDL fluorescence intensity increase in the medium
      during Cu2+-induced LDL oxidation. Cu2+-induced LDL oxidation in the presence of
      100 microM melatonin produced oxidized LDLs that were less recognizable for the
      scavenger receptors of J774 macrophages than were untreated LDLs. Vitamin E, 10
      microM, was more active than 100 microM melatonin in inhibiting LDL oxidation and
      the resulting lipoprotein alterations leading to binding internalization and
      degradation by the J774 macrophages. Vitamin E, 100 microM, inhibited the pursuit
      of the oxidation of oxidized LDL mediated by bovine aortic endothelial cells
      (BAECs) in a culture medium containing Cu2+, whereas 100 microM melatonin had no
      antioxidant effect. Melatonin, 100 microM, as well as 100 microM vitamin E
      inhibited intracellular TBARS formation during the incubation of BAECs with
      highly oxidized LDL but had no influence on the increase in glutathione (GSH)
      concentration during this lengthy exposure (16 h) of BAECs to highly oxidized
      LDL. During this period, the same dose of vitamin E but not of melatonin tended
      to limit the decrease in adenosine triphosphate (ATP) concentration. Vitamin E,
      100 microM, did not significantly reduce cellular lactate dehydrogenase (LDH)
      release in the culture medium during the incubation of oxidized LDL with BAECs,
      whereas 100 microM melatonin dramatically increased this release. These data show
      that melatonin is less active than vitamin E in inhibiting in vitro LDL oxidation
      and does not inhibit the cytotoxicity of oxidized LDL toward cultured endothelial
      cells. The concentrations necessary to inhibit LDL oxidation are far beyond those
      found in human plasma (100 microM vs. 100 pM). Therefore our results indicate
      that the pineal hormone melatonin per se appears to have little antiatherogenic
      property in the in vitro oxidation of LDL and the cytoprotective action against
      the toxicity of oxidized LDL. Nevertheless, in vivo LDL oxidation takes place in
      the subendothelium of the artery wall, and nothing is known about the
      concentration of melatonin or its catabolites in this environment.

PMID- 9781928
TI  - Relationships between heart rate and heart rate variability: study in conscious
      rats.
AB  - Heart rate (HR) and heart rate variability (HRV) are risk markers in cardiac
      disease. HRV is also an index of the sympathovagal modulation of heart rate.
      Their relations have been rarely analyzed. We aimed to study such relations in
      normal adult conscious rats by using a novel bradycardic agent, a sinus node
      inhibitor, S-16257. Placebo-drug crossover designs were used while monitoring HR
      with telemetry and analyzing HRV in both time and frequency domains. S-16257 (2
      mg/kg; n = 10) decreased HR by 29% and markedly increased HRV in parallel. By
      using various combinations of S-16257, atropine (2 mg/kg), and propranolol (4
      mg/kg), a positive relation was shown between RR interval and various indexes of
      HRV: the slower the HR, the greater the HRV. Nevertheless, there is one exception
      to this correlation. When S-16257 was associated with both atropine and
      propranolol, the deep bradycardia was accompanied by a reduction of HRV, which
      indicates that the physiologic negative correlation between HR and HRV is not an
      intrinsic property of the pacemaker but is highly dependent on the two components
      of the autonomic system.

PMID- 9781929
TI  - Perindopril effects on angiotensin I elimination in lung after experimental
      myocardial injury induced by intracoronary microembolization in rats.
AB  - The objective of the study was to determine whether angiotensin (Ang) I
      elimination in lung circulation depends on the degree of myocardial damage with
      and without early long-term perindopril treatment in a rat model of myocardial
      injury induced by intracoronary microembolization. Twenty-one days after surgery,
      steady-state arterial [125I]-Ang I and [125I]-Ang II blood concentrations were
      measured after high-performance liquid chromatography separation during i.v.
      infusion of [125I]-Ang I in three groups of male Wistar conscious rats: (a) sham
      operated rats receiving saline (sham group, n = 6); (b) rats after coronary
      microembolization receiving saline (saline group, n = 7); and (c) rats after
      coronary microembolization receiving perindopril (2 mg/kg/day; from days 2-20
      after embolization; perindopril group, n = 6). Ang I clearance and the Ang I-to
      Ang II concentration ratio (R) were estimated. The embolization per se resulted
      in focal fibrosis, appearance of hypertrophic and dystrophic cardiac myocytes,
      and was accompanied by increased Ang I clearance (1,479 vs. 314 ml/min in sham
      group), 1.8-fold decreased [125I]-Ang II arterial level, and decreased R (0.5 vs.
      1.2 in sham group; p < 0.05). Only Ang I concentrations and R were correlated
      with number of scars (r = -0.77; p < 0.05; and r = -0.82; p < 0.01,
      respectively). Captopril bolus (1 mg/kg, i.v.) caused similar reduction in [125I]
      Ang II blood concentration in both sham and saline groups, but a significant
      increase of [125I]-Ang I blood concentration was detected in the sham group only.
      Thus in rats with coronary microembolization, a higher proportion of Ang I in
      lung circulation is eliminated by pathways independent of angiotensin-converting
      enzyme. In the perindopril group, a reduced number of scars (seven vs. 17 per
      slice in the saline group; p < 0.05), density of dystrophic and hypertrophic
      cardiac myocytes, and increased content of cell glycogen were observed. It was
      accompanied by normalized arterial [125I]-Ang I concentration, Ang I clearance,
      and R; [125I]-Ang II concentration tended to that in sham group. Only in the sham
      and perindopril groups was there significant correlation between Ang I and Ang II
      concentrations. The clear relation between number of scars per slice and R (r = 
      0.83; p < 0.01) was observed in all rats with embolized coronary vessels (saline
      and perindopril groups together). In conclusion, in this experimental, model Ang
      I elimination in the lung circulation was directly related to the degree of
      myocardial damage. Early perindopril treatment prevented maladaptive changes in
      Ang I processing and led to significant reduction of the undesirable aftereffects
      of myocardial tissue damage. Our data demonstrate the cardioprotective action of
      perindopril based on its beneficial influence on the renin-angiotensin system
      disturbances.

PMID- 9781930
TI  - ACE inhibition but not angiotensin II antagonism reduces plasma fibrinogen and
      insulin resistance in overweight hypertensive patients.
AB  - The aim of this study was to compare the effects of the angiotensin-converting
      enzyme (ACE) inhibitor perindopril and the angiotensin II antagonist losartan on
      insulin sensitivity and plasma fibrinogen in overweight hypertensive patients.
      Twenty-eight overweight mild to moderate [diastolic blood pressure (DBP) >90 and
      <110 mm Hg] hypertensives aged 43-64 years, after a 4-week placebo period, were
      randomized to perindopril, 4 mg o.d., or losartan, 50 mg o.d., for 6 weeks. Then,
      after a new placebo period, patients were crossed to the alternative regimen for
      further 6 weeks. At the end of the placebo and of the treatment periods, blood
      pressure was measured, plasma fibrinogen was evaluated, and insulin sensitivity
      was assessed by the euglycemic, hyperinsulinemic clamp technique. Glucose
      infusion rate (GIR) during the last 30 min of clamp and total glucose requirement
      (TGR) were evaluated. Both perindopril and losartan reduced SBP (by a mean of
      20.2 mm Hg, p < 0.001 vs. placebo; and 15.8 mm Hg, p = 0.002 vs. placebo,
      respectively) and DBP (by a mean of 15.2 mm Hg, p = 0.001 vs. placebo, and 11.8
      mm Hg, p = 0.01 vs. placebo respectively), with no difference between the two
      treatments. GIR was significantly increased by perindopril (+2.91 mg/min/kg, p =
      0.042 vs. placebo), but not by losartan (+0.28 mg/min/kg, NS). TGR was not
      modified by losartan but was increased by perindopril (+9.3 g, p = 0.042 vs.
      placebo). Plasma fibrinogen levels were reduced by perindopril (-53.4 mg/dl, p =
      0.022 vs. placebo) but not by losartan (-16.8 mg/dl, NS). The perindopril-induced
      decrease in fibrinogen was correlated with the increase in GIR (r = 0.39; p <
      0.01). These findings suggest that fibrinogen decrease produced by the ACE
      inhibitor is related to its action on insulin sensitivity, which seems to be
      dependent not on angiotensin II blockade but rather on other mechanisms.

PMID- 9781931
TI  - Protection of neuronal uptake-1 inhibitors in ischemic and anoxic hearts by
      norepinephrine-dependent and -independent mechanisms.
AB  - Cardiac ischemia and anoxia induce massive norepinephrine (NE) release, which is
      mediated by a reverse operation of uptake-1 and can be suppressed by uptake-1
      inhibitors. We studied effects of uptake-1 inhibitors on incidence of ventricular
      fibrillation (VF%) and myocardial contracture in perfused rat hearts under
      ischemic or anoxic conditions. NE release occurred in hearts during ischemia or
      anoxia and was largely inhibited by desipramine, imipramine, and cocaine. The
      generation of inositol 1,4,5-trisphosphate (InsP3) during reperfusion also was
      abolished by desipramine. During anoxia/reoxygenation, VF (93 and 71%,
      respectively) and myocardial contracture occurred and were significantly
      inhibited by desipramine and by NE depletion. Regional ischemia and reperfusion
      induced high VF% (86 and 100%, respectively), which was reduced or abolished by
      desipramine and imipramine at 0.03 and 0.3 microM. During the ischemic phase,
      cocaine was similarly antiarrhythmic, as was a combination of timolol and
      prazosin, but NE depletion was not. In NE-depleted hearts, cocaine or the
      combination of timolol and prazosin showed limited effect on VF%, whereas both
      desipramine and imipramine abolished VF. In anesthetized rats in vivo, ischemic
      VF% was reduced by desipramine (30 vs. 92%; p < 0.01). In conclusion, uptake-1
      inhibitors protect hearts against ischemia/reperfusion- and anoxia/reoxygenation
      induced arrhythmias, partly because of the inhibition of locally mediated NE
      release. Other actions of desipramine and imipramine may contribute to the
      overall efficacy.

PMID- 9781933
TI  - Vasopressin dilates the rat carotid artery by stimulating V1 receptors.
AB  - The acute effects of various vasopressor agents on the diameter of the common
      carotid artery were studied in halothane-anesthetized normotensive rats. The
      animals were infused intravenously for 60 min with equipressor doses of
      angiotensin II (10 ng/min), the alpha1-stimulant methoxamine (5 microg/min),
      lysine vasopressin (5 mU/min), or vehicle. The arterial diameter was measured by
      using a high-resolution ultrasonic echo-tracking device. The three
      vasoconstrictors increased the carotid artery diameter, but this effect was
      significantly more pronounced with lysine vasopressin. Even a nonpressor dose of
      lysine vasopressin (1 mU/min) caused a significant increase in the arterial
      diameter. The lysine vasopressin-induced vasodilatation could be prevented by the
      administration of d(CH2)5Tyr(Me)AVP (10 microg, i.v.), a selective V1
      vasopressinergic receptor antagonist. These data therefore suggest that a short
      term increase in blood pressure induces in rats a distention of the carotid
      artery. The increase in arterial diameter seems to involve an active mechanism
      with lysine vasopressin caused by the stimulation of V1-vasopressinergic
      receptors.

PMID- 9781932
TI  - Saterinone, dobutamine, and sodium nitroprusside: comparison of cardiovascular
      profiles in patients with congestive heart failure.
AB  - The acute hemodynamic effects of the phosphodiesterase (PDE) III inhibitor
      saterinone were compared with dobutamine and sodium nitroprusside in 12 patients
      with idiopathic congestive cardiomyopathy (NYHA III). Hemodynamic measurements
      were obtained with a Swan-Ganz thermodilution catheter. At the peak of its dose
      response curve, saterinone induced an increase in cardiac index (+102%), stroke
      volume (+97%), and heart rate (+6%), paralleled by a decrease in pulmonary
      capillary wedge pressure (-46%), right atrial pressure (-51%), pulmonary arterial
      pressure (systolic -32%, diastolic -45%, mean -38%), systemic blood pressure
      (systolic -3%, diastolic -13%, mean -9%), systemic vascular resistance (-54%),
      and pulmonary vascular resistance (-58%). Dobutamine had similar effects on
      cardiac index (+106%) and stroke volume (+87%) but lacked vasodilatory
      characteristics. In contrast to dobutamine, both nitroprusside and saterinone
      demonstrated more pronounced vasodilatory effects. Nitroprusside was less
      effective on cardiac index (+66%) and stroke volume (+56%) than was saterinone.
      The double product was markedly increased by dobutamine (+28%), did not change
      with saterinone treatment (+2%), and decreased with nitroprusside (-10%). This
      indicates that according to double product, only the application of dobutamine
      caused a relevant increase in myocardial oxygen consumption. Saterinone was
      demonstrated to be a safe and potent drug on short-term application; it combines
      the vasodilating properties of sodium nitroprusside with the positive inotropic
      effects of dobutamine without major changes in myocardial oxygen consumption.

PMID- 9781934
TI  - Endothelium-derived hyperpolarizing factor activates Ca2+-activated K+ channels
      in porcine coronary artery smooth muscle cells.
AB  - Although endothelium-derived hyperpolarizing factor (EDHF) activity has been
      demonstrated in arteries from various species, EDHF has not been chemically
      identified, nor its mechanism of action characterized. To elucidate this
      mechanism, we tested the effect of EDHF on large-conductance Ca2+-activated K+
      (K(Ca)) channels in porcine coronary artery smooth muscle cells. By using a patch
      clamp technique, single-channel currents were recorded in cultured smooth muscle
      cells; the organ bath also contained a strip of porcine coronary with
      endothelium, which served as the source of endothelium-derived relaxing factor(s)
      including EDHF. Exposure of endothelium to 10(-6) M bradykinin activated K(Ca)
      channels in cultured smooth muscle cells in cell-attached patches. When the
      experiment was performed in the presence of 10 microM indomethacin and 30 microM
      N(G)-nitro-L-arginine (L-NNA), which block the generation of prostaglandin I2
      (PGI2) and NO, respectively, K(Ca) channel activity was stimulated by bradykinin,
      indicating the direct involvement of EDHF in K(Ca) channel stimulation. Neither
      10 microM methylene blue nor 25 microM Rp-cAMPS inhibited bradykinin-induced
      K(Ca) channel activity. In inside-out patches, the addition of bradykinin to the
      solution was without effect on K(Ca) channel activation. However, in the presence
      of 0.5 mM guanosine triphosphate (GTP) and 1.0 mM adenosine triphosphate (ATP) in
      the bath solution, K(Ca) channels was activated by bradykinin. In outside-out
      patches, the addition of bradykinin also increased K(Ca) channel activity, when
      GTP and ATP were added to the pipette solution. The addition of GDP-beta-S (100
      microM) in the cytosolic solution completely blocked the activation K(Ca)
      channels induced by bradykinin in inside-out and outside-out patches.
      Pretreatment with 30 microM quinacrine, a phospholipase A2 inhibitor, or 3 microM
      17-octadecynoic acid (17-ODYA), a cytochrome P450 inhibitor, in addition to
      indomethacin and L-NNA, abolished bradykinin-stimulated K(Ca) channel activity in
      cell-attached patches. Both 14,15-epoxyeicosatrienoic acid (EET) and 11,12-EET
      increased the open probabilities of K(Ca) channels in cell-attached patches.
      These results suggest that EDHF, released from endothelial cells in response to
      bradykinin, hyperpolarizes smooth muscle cells by opening K(Ca) channels.
      Furthermore, our data suggest that EDHF is an endothelium-derived cytochrome P450
      metabolite of arachidonic acid. The effect of EDHF on K(Ca) channels is not
      associated with an increase of cAMP and cGMP. The activation of K(Ca) channels
      appears to be due to the activation of GTP-binding protein.

PMID- 9781935
TI  - L-Cysteinesulfinic acid modulates cardiovascular function in the periaqueductal
      gray area of rat.
AB  - L-Cysteinesulfinic acid (CSA) involvement in modulating periaqueductal gray (PAG)
      pressor neurons has been evaluated in the rat. Intra-PAG CSA induced an increase
      in mean blood pressure partially antagonized by (2S)-alpha-ethylglutamic acid
      (EGA), a group II metabotropic glutamate receptors (mGluRs) antagonist.
      Conversely, the NMDA antagonist, DL-AP5, or the mGluRs antagonists, (+)-MCPG,
      UPF523, or (RS)-alpha-methylserine-O-phosphate (MSOP), were devoid of any
      activity on the CSA effect. These data show that the excitatory amino acid CSA,
      probably by stimulating an mGluR, contributes with glutamate in modulating
      cardiovascular function at the PAG matter.

PMID- 9781937
TI  - Inhibition of angiotensin II-induced contraction by losartan in human coronary
      arteries.
AB  - The in vitro effects of angiotensin II (Ang II) in human vessels are not well
      studied. The development of specific Ang II-receptor antagonists has made it
      possible to delineate more carefully the receptor mechanisms involved. The
      objective of this study was twofold: to investigate the effect of Ang II on human
      coronary arteries and to study the effects of angiotensin II type 1 receptor
      blockade with losartan. The setting was contractile experiments with ring
      segments of coronary arteries. We observed that Ang II is a vasoconstrictor of
      human coronary arteries, with a pEC50 value of 9.26 +/- 0.22 and Emax of 68.7 +/-
      9.61% of potassium-induced contraction. Losartan (10-100 nM) shifted the
      concentration-response curve of Ang II to the right, with pEC50 values of 7.64 +/
      0.10 and 7.00 +/- 0.15, respectively (p = 0.001), demonstrating the antagonistic
      properties of losartan. We also noted a decreased maximal response to Ang II
      after incubation of losartan, with Emax of 51.1 +/- 7.08% and 41.9 +/- 4.70% (p =
      0.05), respectively. In conclusion, this is the first report describing the
      contractile effect of Ang II and the antagonizing effects of losartan in isolated
      human coronary arteries.

PMID- 9781936
TI  - Desethylamiodarone prolongation of cardiac repolarization is dependent on gene
      expression: a novel antiarrhythmic mechanism.
AB  - Desethylamiodarone (DEA) is the major metabolite of amiodarone and has similar
      electrophysiologic effects with prolongation of the repolarization that is
      reversed by thyroid hormone (T3). Some of the electrophysiologic effects are
      probably due to antagonism of T3 at the receptor level. Such effects of T3 are
      mediated by modulation of gene transcription. The aim of this study was to
      investigate whether cycloheximide (Cy), an inhibitor of protein synthesis, and
      actinomycin D (ActD), a RNA-synthesis inhibitor, block DEA-induced prolongation
      of the repolarization and whether DEA takes part in the autoregulation of the
      nuclear thyroid hormone-receptor subtypes (ThR). Corrected monophasic action
      potentials (MAPc) and QTc were measured in Langendorff-perfused guinea pig hearts
      for 1 h. The hearts were continuously perfused with (a) vehicle, (b) 7.5 microM
      Cy, (c) 5 microM DEA, (d) 5 microM DEA + 7.5 microM Cy, (e) 1 microM T3, (f) 5
      microM DEA + 1 microM T3, (g) 1.5 microM ActD, and (h) ActD + DEA. A potassium
      channel blocker with class III antiarrhythmic effects, 0.5 microM almokalant, was
      used as a control, separately and together with Cy. Western blot analysis for the
      ThR subtypes alpha, beta1, and beta2 was performed on vehicle- and DEA-treated
      hearts. DEA increased MAPc by 19% (p < 0.0005) and QTc by 18% (p < 0.0005). There
      was no effect on MAPc or QTc when Cy, ActD, or T3 was added with DEA. Almokalant
      increased MAPc by 14% (p < 0.005) and QTc by 13% (p < 0.0005). When Cy was
      present, almokalant still induced a similar prolongation of MAPc by 14% (p <
      0.005) and QTc by 17% (p < 0.0005). Western blot analysis revealed no change in
      the expression of the ThR protein. In conclusion, the prolongation of the cardiac
      repolarization by DEA, but not almokalant, can be totally blocked by Cy and ActD.
      This indicates that the class III action of DEA is at least in part dependent on
      transcription rather than a direct effect on cell-membrane channels or receptors.
      The action of DEA could be reversed by T3, indicating an antagonism between DEA
      and T3. These results suggest a new antiarrhythmic mechanism dependent on gene
      expression.

PMID- 9781938
TI  - Dexamethasone modulates the expression of endothelin-1 and -A receptors in A7r5
      vascular smooth muscle cells.
AB  - Endothelin-1 (ET-1) is synthesized and released by vascular smooth-muscle cells
      (VSMCs). Glucocorticoids induce the release of ET-1 from VSMCs into the medium.
      We investigated whether glucocorticoids modulate ET-1 action by an autocrine
      production of ET-1 in A7r5 VSMCs. Dexamethasone (100 nM) stimulated the release
      of ET-1 into the medium. Treatment with 100 nM dexamethasone for 24 h reduced the
      peak increase of intracellular free Ca2+ induced by ET-1 (100 nM) by 50%, an
      effect that was dose-dependently inhibited by the specific ET(A)-receptor
      antagonist FR139317. Scatchard plots of [125I]-ET-1 binding revealed that
      dexamethasone reduced the number of maximal ET-1 binding sites without altering
      their binding affinity. FR139317 reversed the decrease in ET-1 binding capacity
      induced by dexamethasone. Northern blot analysis revealed that dexamethasone
      increased the level of prepro-ET-1 messenger RNA (mRNA) and decreased the level
      of ET(A)-receptor mRNA. FR139317 prevented the decrease in the level of ET(A)
      receptor mRNA induced by dexamethasone. Results indicate that dexamethasone
      downregulates ET(A) receptors in A7r5 VSMCs at the mRNA level, in part by the
      autocrine production of ET-1.

PMID- 9781939
TI  - Twenty-four hour antihypertensive efficacy of indapamide, 1.5-mg sustained
      release: results of two randomized double-blind controlled studies.
AB  - The antihypertensive efficacy of a 1.5-mg sustained-release formulation (SR 1.5)
      of indapamide, a diuretic related to thiazide, has been pointed out by using
      conventional sphygmomanometric measurement 24 h after dosing in clinic, in two
      large European randomized, double-blind, controlled studies (2 and 3 months). One
      of these studies was then extended to 12 months, as a complementary open study.
      Quality-controlled ambulatory blood pressure monitoring (ABPM) data for a total
      of 216 patients from these studies are presented, including subgroups of
      hypertensives and responders. Indapamide SR 1.5 achieves an adequate 24-h blood
      pressure control by significantly reducing the 24-h, diurnal, and nocturnal blood
      pressures versus baseline, confirming the sphygmomanometric data. The benefit at
      2 and 3 months is maintained at 1 year, which confirms the long-term efficacy of
      SR 1.5 mg. The trough-to-peak ratio--not previously calculated for a diuretic
      according to international guidelines--meets Food and Drug Administration
      requirements and confirms the 24-h efficacy of indapamide SR 1.5.

PMID- 9781940
TI  - The emerging role of retinoids and retinoic acid metabolism blocking agents in
      the treatment of cancer.
AB  - BACKGROUND: Although significant advances have been made in the treatment of some
      malignancies, the prognosis of patients with metastatic tumors remains poor.
      Differentiating agents redirect cells toward their normal phenotype and therefore
      may reverse or suppress evolving malignant lesions or prevent cancer invasion. In
      addition, they offer a potential alternative to the classic cytostatic drugs.
      METHODS: The purpose of this review was to examine the current and potential
      future roles of differentiating agents in the treatment of cancer. RESULTS:
      Initial studies with differentiating agents focused on retinoid therapy. Although
      retinoids have shown some clinical success, their widespread use has been limited
      by resistance and, in the chemopreventive setting, toxicity. This has led to the
      synthesis of a number of new retinoids that currently are undergoing clinical
      investigation. A further approach to overcoming the drawbacks associated with
      exogenous retinoids has been to increase the levels of endogenous retinoic acid
      (RA) by inhibiting the cytochrome P450-mediated catabolism of RA using a novel
      class of agents known as retinoic acid metabolism blocking agents (RAMBAs).
      Liarozole, the first RAMBA to undergo clinical investigation, preferentially
      increases intratumor levels of endogenous RA resulting in antitumor activity.
      CONCLUSIONS: Although studies using exogenous retinoids in this setting have not
      yet fulfilled their initial promise, studies with a growing set of synthetic
      retinoids are ongoing. Furthermore, modulation of endogenous retinoids may offer
      a significant new potential treatment for cancer.

PMID- 9781941
TI  - Alcohol consumption enhances liver metastasis in colorectal carcinoma patients.
AB  - BACKGROUND: It is important to identify risk factors for liver metastasis in
      patients with colorectal carcinoma because the liver is the most common site of
      recurrence. Alcohol consumption reportedly is associated with hematogenous
      metastasis in certain animal models. Furthermore, some studies have shown that
      carmofur, a derivative of 5-fluorouracil, is particularly effective as adjuvant
      chemotherapy for colorectal carcinoma, and may even suppress liver metastasis,
      although the mechanism by which this occurs remains unknown. In addition,
      carmofur is known to inhibit alcohol metabolism. To the authors' knowledge, the
      relation between liver metastasis in colorectal carcinoma and alcohol consumption
      has not been examined previously. Therefore, the authors studied the relations
      between liver metastasis in colorectal carcinoma and various clinicopathologic
      factors including alcohol consumption status. METHODS: This study was comprised
      of 133 colorectal carcinoma patients with invasion beyond the submucosal layer
      who had undergone surgical resection. The subjects were examined and divided into
      two groups according to the occurrence or absence of liver metastasis. The
      relations between liver metastasis and other clinicopathologic factors were
      analyzed by univariate and multivariate statistical methods. RESULTS: Univariate
      analysis showed alcohol consumption (P=0.0021) and blood vessel invasion
      (P=0.0045) were correlated with liver metastasis. Multivariate analysis showed
      both to be independent risk factors for liver metastasis. CONCLUSIONS: Alcohol
      consumption is an independent risk factor for liver metastasis in colorectal
      carcinoma patients. Therefore, patients with colorectal carcinoma who drink
      alcohol require intensive examination and follow-up with respect to liver
      metastasis. Further study is necessary to confirm the effect of adjuvant
      chemotherapy using carmofur in colorectal carcinoma patients.

PMID- 9781942
TI  - Hepatitis C virus infection associated with human hepatocellular carcinoma: lack
      of correlation with p53 abnormalities in Caucasian patients.
AB  - BACKGROUND: Several lines of evidence indicate that there is a close association
      between hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC).
      However, the role of the virus itself in the development of the disease is not
      yet well understood. METHODS: In liver samples from 15 anti-HCV positive
      Caucasian patients with HCC, the authors searched for the presence and genomic
      characteristics of the infecting virus, and also analyzed the p53 gene by single
      strand conformation polymorphism and sequencing of abnormal bands. RESULTS: In
      all cases but one, HCV RNA was detected in nonneoplastic liver tissue, whereas in
      neoplastic tissue, viral sequences were detected in 6 of 6 samples containing
      moderately differentiated HCC (Edmondson grades I-II) and in 2 of 9 containing
      poorly differentiated HCC (Edmondson grade III) (P=0.007). Seventy-three percent
      of the cases were infected by genotype 1 and 20% by genotype 2, whereas the liver
      cells of 1 patient with a previous history of hepatitis B infection were HCV RNA
      negative. p53 mutations, observed in 2 patients, consisted of a G-to-A transition
      at codon 176 of exon 5 in 1 patient and a G-to-T transversion at codon 287 of
      exon 8 in the other. CONCLUSIONS: The results of this study indicate that HCV may
      contribute to liver tumor development during the early stages of carcinogenesis,
      whereas p53 gene mutations were detected only in 2 of 15 patients in this cohort.

PMID- 9781943
TI  - Thymoma: prognostic factors and treatment outcomes.
AB  - BACKGROUND: The objective of this study was to establish prognostic factors for
      thymoma and determine the impact of surgery with or without postoperative
      radiotherapy. METHODS: Seventy patients treated at the University Hospital
      Dusseldorf during the period 1954-1991 were retrospectively studied. All thymoma
      patients underwent surgery, 22 received postoperative radiotherapy, and 3 also
      received chemotherapy. According to thymoma staging as described previously by
      Masaoka et al., 21% were Stage I, 26% Stage II, 43% Stage III, 7% Stage IVA, and
      3% Stage IVB. Lymphocytic type disease was found in 36% of patients,
      lymphoepithelial type in 33%, epithelial type in 23%, and spindle cell type in
      9%. The relevance of Karnofsky performance status (KPS), gender, age, myasthenia
      gravis, histology, tumor size, and stage to survival was determined by univariate
      analysis, and their independent significance was tested by multivariate analysis.
      Survival rates were calculated using the Kaplan-Meier method and the log rank
      test. RESULTS: In univariate analysis, KPS (P < 0.001), histologic type
      (P=0.0093), and stage (P=0.0001) proved to be significant predictors of overall
      survival. Spindle cell type was associated with the best and epithelial type the
      worst prognosis; patients with the latter type had a 5-year survival rate of 30%.
      Multivariate analysis revealed that stage, histology, and KPS were predictive of
      overall survival. In Stages III and IV, relapses were reduced by postoperative
      radiotherapy from 50% to 20%. The site of relapse was outside the irradiated area
      in 80% of patients. Disease free survival (P=0.36) and median survival (P=0.72)
      of patients with completely resected advanced thymomas did not differ from that
      for patients with incompletely resected tumors who received radiotherapy.
      CONCLUSIONS: Postoperative radiotherapy can improve local control in patients
      with advanced thymoma. Survival after incomplete resection is not compromised
      when postoperative radiotherapy is employed. KPS should be considered an
      important prognostic factor in future studies.

PMID- 9781944
TI  - Skeletal and extraskeletal myxoid chondrosarcoma: a comparative
      clinicopathologic, ultrastructural, and molecular study.
AB  - BACKGROUND: Skeletal myxoid chondrosarcoma (SMC) is considered to be either a
      typical chondrosarcoma with prominent myxoid alterations or an altogether unique
      malignant cartilage tumor. Extraskeletal myxoid chondrosarcoma (EMC) is a
      relatively rare but well-recognized neoplasm. It was initially thought to be a
      low grade sarcoma of cartilage derivation and was recently found, in most cases,
      to contain a reciprocal t(9;22), resulting in a fusion of the EWS and CHN genes.
      Are SMC and EMC the same entity arising in two different locations, or are they
      two separate entities? To the authors' knowledge, this study represents the first
      systematic attempt to answer this question. METHODS: Forty consecutive cases of
      EMC (20 cases) and SMC (20 cases) were compared by light and electron microscopy,
      immunohistochemistry, and molecular analysis. The mean clinical follow-up for
      both groups was 55 months. Histologic criteria for SMC consisted of 95% myxoid
      matrix, with only minimal hyaline cartilage formation. RESULTS: The gender
      distribution was identical in both groups (13 males and 7 females). The mean age
      was 55 years for EMC patients and 45 years for SMC patients. The EMC tumors were
      predominantly located in the deep soft tissues of the lower extremity (60%) and
      buttock (20%), and the mean tumor size was 13 cm. SMC was most commonly located
      in the bones around the hip joint (pelvis 35%; proximal femur 20%) and shoulder
      (20%); the mean size was 9 cm. Histologic grade in the EMC group correlated with
      survival (82% of the high grade tumors metastasized). Electron microscopy
      performed in 8 EMC cases revealed intracisternal microtubules in 3 cases and
      prominent mitochondria in 5, whereas in 5 SMC cases it revealed only
      inconspicuous organelles. Molecular analysis for the EWS-CHN fusion RNA resulting
      from the t(9;22) was performed in 15 cases (9 EMC and 6 SMC) and was detected in
      7 of 9 EMC cases and 0 of 6 SMC cases. In one case, the molecular structure of
      the EWS-CHN fusion RNA was novel. The probability of metastasis was significantly
      higher (P=0.004) for the EMC group than for the SMC group. CONCLUSIONS: Although
      similar light microscopic features are noted in EMC and SMC, fundamental
      differences are noted at the ultrastructural and molecular levels, suggesting
      that EMC and SMC represent two distinct entities in the chondrosarcoma family of
      tumors.

PMID- 9781945
TI  - Extramedullary involvement in patients with acute promyelocytic leukemia: a
      report of seven cases.
AB  - BACKGROUND: Extramedullary involvement is only occasionally observed in patients
      with acute promyelocytic leukemia (APL) but has been said to occur more
      frequently after treatment with all- trans retinoic acid (ATRA) than after
      treatment with cytotoxic drugs. In the literature, 37 well-documented cases have
      been reported. METHODS: The authors report 7 patients with extramedullary APL
      documented by cytologic, phenotypic, and molecular analyses among 120 adult APL
      patients referred to two different institutions during a period of 9 years.
      RESULTS: In this APL series, extramedullary disease (EMD) occurred in 7 of 120
      cases (5.8%). The extramedullary sites were the skin in five patients, the
      central nervous system in one, and the lymph nodes in one. Molecular analysis of
      the PML/RARalpha rearrangement was performed on four samples of skin and one of
      CSF; all patients exhibited the same molecular pattern in the bone marrow (BM)
      and EMD sites. Of 120 patients, 61 were treated with ATRA plus chemotherapy and
      59 with chemotherapy alone. Relapses were observed in 38 patients, 6 of whom had
      EMD; 1 patient had developed EMD at the onset of APL. Of the relapsed EMD cases,
      2 of 61 patients had received ATRA plus chemotherapy and 4 of 59 had received
      chemotherapy alone. CONCLUSIONS: There is some controversy as to whether
      treatment of APL with ATRA may predispose patients to the development of
      extramedullary relapse. The data from this study do not contain evidence that EMD
      may occur more frequently in APL patients treated with ATRA.

PMID- 9781947
TI  - A Phase I dose escalation trial of continuous infusion paclitaxel to augment high
      dose cyclophosphamide and thiotepa plus stem cell rescue for the treatment of
      patients with advanced breast carcinoma.
AB  - BACKGROUND: Paclitaxel, an effective chemotherapeutic agent in the management of
      breast carcinoma, may have activity in women whose disease has recurred after
      high dose chemotherapy. With this is mind the authors explored the addition of a
      120-hour continuous infusion of paclitaxel to a previously reported regimen
      comprised of high dose cyclophosphamide and thiotepa. METHODS: Thirty-one women
      with advanced breast carcinoma (30 patients with Stage IV disease and 1 patient
      with Stage IIIB disease) underwent harvest and cryopreservation of bone marrow
      and/or peripheral blood progenitor cells. High dose cyclophosphamide (2.5 g/m2)
      and thiotepa (225 mg/m2) were administered intravenously on Days -7, -5, and -3.
      Paclitaxel was administered as a 120-hour continuous infusion starting on Day -7.
      RESULTS: Three patients were treated at the initial cohort dose of 50 mg/m2 (over
      120 hours), 6 patients at 100 mg/m2, 6 patients at 125 mg/m2, 6 patients at 150
      mg/m2, 6 patients at 180 mg/m2, and 4 patients at 210 mg/m2. All patients
      completed the treatment protocol as planned with no associated transplant-related
      deaths. Mucositis as evidenced by either stomatitis or noninfectious diarrhea was
      experienced by all patients and was determined to be the dose-limiting toxicity
      at the 210 mg/m2 dose level. One patient with dose-limiting mucositis required
      intubation for airway protection and also experienced Grade 3 (according to the
      Cancer and Leukemia Group B common toxicity grading scale) pulmonary and
      neurologic toxicity. Only one Grade 3 toxicity was encountered below the maximum
      tolerated dose in a patient who developed diffuse alveolar hemorrhage at a dose
      of 125 mg/m2. No allergic reactions or clinical evidence of peripheral
      neuropathies were encountered. Cardiac, hepatic, and renal toxicities were
      minimal. Response rates in this previously treated patient population were
      difficult to assess in light of the high incidence of bone metastases; an overall
      response rate of 24% was obtained. CONCLUSIONS: Paclitaxel at a dose of 180 mg/m2
      as a 120-hour continuous infusion may be added safely to high dose
      cyclophosphamide and thiotepa with autologous stem cell rescue. Further studies
      are ongoing to evaluate the efficacy and further define the toxicity of this
      recommended Phase II dose.

PMID- 9781946
TI  - The importance of the histologic grade of invasive breast carcinoma and response
      to chemotherapy.
AB  - BACKGROUND: Histologic grade is well recognized for its prognostic significance
      in cases of primary operable invasive breast carcinoma; however, the majority of
      studies in which grade has been assessed have been based on single-center trials.
      In addition, the role of grade in predicting response to chemotherapy has not
      been examined in many previous studies. METHODS: The authors assessed the value
      of Nottingham histologic grade (NHG) in a group of 465 patients enrolled in a
      multicenter, randomized International Breast Cancer Study Group clinical trial of
      adjuvant chemotherapy for patients with lymph node (LN) positive and LN negative
      primary breast carcinoma (formerly named Ludwig Trial V). RESULTS: NHG was a
      predictor of overall survival for both LN negative and LN positive patients
      (P=0.045 and P < 0.001, respectively). NHG was associated with a poorer prognosis
      for both LN positive and LN negative patients, with hazard ratios of 1.651 (P <
      0.001) and 1.437 (P=0.045), respectively, for an increase of one grade. Among LN
      negative patients, this survival disadvantage was observed only for those who
      received perioperative chemotherapy. For LN positive patients, an increase of one
      grade resulted in a significant overall survival disadvantage regardless of
      whether prolonged or perioperative chemotherapy was given. For LN negative
      patients grouped by grade, there was no observed difference in overall or disease
      free survival according to whether perioperative chemotherapy or no adjuvant
      therapy was given. However, LN positive patients with Grade 3 tumors had a
      significantly greater overall and disease free survival benefit from prolonged
      chemotherapy than from perioperative chemotherapy (P=0.016 and P=0.013,
      respectively); LN positive patients with Grade 1 or 2 disease in both treatment
      arms had comparable overall and disease free survival. A strong correlation
      between the previously utilized Bloom-Richardson grading system (BRG) and NHG was
      observed (P < 0.001 and kappa=82%) and no apparent differences in overall and
      disease free survival were observed between the two systems. NHG did, however,
      identify a greater proportion of tumors as Grade 1, and BRG identified a greater
      proportion of breast carcinomas as Grade 3. CONCLUSIONS: This multicenter
      clinical study confirms the value of histologic grade, and the authors propose
      that this technique be used to identify Grade 3, LN positive patients who will
      benefit from prolonged rather than perioperative chemotherapy.

PMID- 9781948
TI  - Cancer of the corpus uteri in white and black women in Michigan, 1985-1994: an
      analysis of trends in incidence and mortality and their relation to histologic
      subtype and stage.
AB  - BACKGROUND: Cancer of the corpus uteri occurs more commonly among white women in
      the U.S., yet survival is poorer for black women. This study examined whether
      this trend has changed and also examined the relation of age and histologic
      subtype to differences in stage. METHODS: This retrospective cohort study
      assessed incidence trends, mortality trends, and the relation of age and
      histologic subtype to stage for 12,079 incident cases and 2325 deaths registered
      between 1985 and 1994 in Michigan. Rate ratios compared incidence and mortality.
      Odds ratios quantified the contribution of age and histologic subtype to
      differences in risk for advanced stage, using Mantel-Haenszel univariate
      techniques and multivariate logistic regression. RESULTS: The overall incidence
      rate was 21.99 per 100,000, and the overall mortality rate was 3.82 per 100,000.
      Black women had a 40% lower risk (rate ratio [RR] =0.60) of developing cancer of
      the corpus uteri but had a 54% greater risk (RR=1.54) of dying from cancer of the
      corpus uteri. Black women were at greater risk of being diagnosed with either
      sarcoma or more aggressive adenocarcinoma. However, after adjustment for age and
      histologic subtype, black women still had an increased risk for advanced stage
      disease (2.63, 95% confidence interval=2.19-3.16). CONCLUSIONS: The disparity
      between white and black women persists in incidence and mortality trends for
      cancer of the corpus uteri. The greater frequency of more aggressive histologic
      subtypes experienced by black women accounts for only 10% of their excess risk
      for more advanced stage disease.

PMID- 9781949
TI  - Patients with ovarian carcinoma upstaged to stage III after systematic
      lymphadenctomy have similar survival to Stage I/II patients and superior survival
      to other Stage III patients.
AB  - BACKGROUND: Patients with epithelial ovarian carcinoma upstaged from Stage I/II
      to Stage IIIC based on lymph node involvement are known to have poor prognoses.
      The authors investigated whether systematic aortic and pelvic lymphadenectomy
      would affect the prognoses of these patients. METHODS: During the period 1987
      1996, 103 patients in Stage I-III underwent optimal cytoreductive surgery with
      systematic aortic and pelvic lymphadenectomy at initial surgery. All patients
      except for those in Stage IA received adjuvant cisplatin-based chemotherapy after
      surgery. Of 67 patients with intraperitoneal tumors limited to the pelvis, 14
      were upstaged to Stage III based on lymph node positivity (Group A). The authors
      compared the survival of Group A patients with that of 53 patients who had
      intraperitoneal tumors limited to the pelvis and negative lymph nodes (Group B),
      and also with that of 36 patients who had intraperitoneal tumors beyond the
      pelvis irrespective of lymph node status (Group C). RESULTS: The 5-year survival
      of Group A patients in Stage III based only on lymph node positivity had fairly
      good survival, although it was not significantly different from that of Group B
      patients in Stage I/II (84% vs. 96%, P=0.107). Group A had much better 5-year
      survival than Group C patients who were considered to be Stage III because they
      had intraperitoneal tumors beyond the pelvis (84% vs. 26%, P=0.042). CONCLUSIONS:
      Relatively good survival was observed for patients with intraperitoneal tumors
      limited to the pelvis and lymph node involvement who underwent systematic aortic
      and pelvic lymphadenectomy.

PMID- 9781950
TI  - The effect of combined androgen blockade on bone turnover and bone mineral
      densities in men treated for prostate carcinoma: longitudinal evaluation and
      response to intermittent cyclic etidronate therapy.
AB  - BACKGROUND: Androgen receptor blocking agents have become an established form of
      therapy for men with disseminated prostate carcinoma. The purpose of this study
      was to evaluate markers of bone turnover and to measure bone mineral densities
      (BMD) in men with disseminated prostate carcinoma treated with combined androgen
      blockade prior to and after 6 months of intermittent cyclic etidronate therapy.
      METHODS: Twelve consecutive men with disseminated prostate carcinoma were
      evaluated at 0, 6, and 12 months after treatment with a long acting gonadotropin
      releasing hormone agonist (goserelin acetate) and an androgen antagonist
      (flutamide). During the 6-12 month period, patients were treated with adjuvant
      intermittent cyclic etidronate therapy and calcium supplementation. Lumbar spine
      BMD was measured by spinal quantitative computed tomography (QCT) and femoral
      neck BMD by dual energy X-ray absorptiometry (DXA). RESULTS: Combined androgen
      blockade resulted in all men achieving serum free testosterone concentrations of
      <2.2 pmol/L (normal range, 38-114 pmol/ L). The mean serum prostate specific
      antigen activities decreased from 130.8+/-46 to 6.9+/-4.4 ng/mL (P < 0.05).
      Although serum calcium, parathyroid hormone, and 25-hydroxyvitamin D measurements
      remained unchanged, serum bone Gla-protein concentrations and urinary
      deoxypyridinolene excretion rates increased significantly (P < 0.01,
      respectively). Mean lumbar spine QCT decreased by 6.6+/-1.5% from 76.5 mg/cm3
      (95% confidence interval [95% CI, 57-96 mg/cm3) to 73.9 mg/cm3 (95% CI, 55-93
      mg/cm3) (P < 0.001) and mean femoral neck DXA decreased by 6.5+/-1.3% from 0.94
      g/cm2 (95% CI, 0.81-1.07 g/cm2) to 0.91 g/cm2 (95% CI, 0.79-1.04 g/cm2) (P <
      0.001). After treatment with adjuvant intermittent cyclic etidronate, mean lumbar
      spine QCT increased by 7.8+/-3.7% to a final value of 75 mg/cm3 (95% CI, 48.7-101
      mg/cm3) (P=0.001 compared with the initial 6 months without intermittent cyclic
      etidronate therapy). Significant increases in BMD also were observed in the
      femoral neck and Ward's triangle. CONCLUSIONS: Androgen receptor blocking agents
      have an established role in the treatment of disseminated prostate carcinoma.
      However, combined androgen blockade in elderly men with disseminated prostate
      carcinoma results in high bone turnover with significant cancellous bone loss.
      The results of this study show that adjuvant therapy with intermittent cyclic
      etidronate may prevent these changes and decrease the risk of spinal fractures.

PMID- 9781951
TI  - Predicting the pathology results of radical prostatectomy from preoperative
      information: a validation study.
AB  - BACKGROUND: There are now over 13 published models for predicting the outcomes of
      radical prostatectomy using preoperative information. Because their ability to
      predict the pathology of the prostatectomy is key in deciding who benefits the
      most from this surgery, it is important to know how well these models work for
      new data. METHODS: The patients in this study were 100 men diagnosed with
      prostate carcinoma in the prostate specific antigen (PSA)-based screening program
      at Washington University Medical Center. To test the models, the authors used
      preoperative information and the published algorithms to predict postoperative
      pathology outcomes. Statistical methods included plots of predicted probability
      against observed probability, boxplots of predicted probability against observed
      outcomes, logistic regression, and linear regression. RESULTS: Although none of
      the published models predicted the outcomes of radical prostatectomy perfectly,
      those that predicted tumor volume performed best, and in general those that were
      multivariate also performed best. Nevertheless, the ability of any of these
      models to discriminate binary outcomes was not very great. CONCLUSIONS: The
      results of this study suggest that preoperative variables based on serum PSA and
      the results of needle biopsies can be used in multivariate models to predict
      tumor volume, but these models need to be improved. Predicting locally advanced
      tumor stage is likely to be more difficult and may require information beyond
      what needle biopsies can provide.

PMID- 9781952
TI  - Atypical angiomyolipoma of the kidney: a distinct morphologic variant that is
      easily confused with a variety of malignant neoplasms.
AB  - BACKGROUND: The purpose of this study was to fully characterize and emphasize the
      salient features of an unusual variant of angiomyolipoma that the authors believe
      has been underrecognized. METHODS: Five cases of atypical angiomyolipoma (AAML)
      of the kidney, two of which were reported previously, were retrieved from the
      consultation files of one of the authors. In one patient a small extrarenal tumor
      was examined in addition to the primary renal tumor. The histopathologic features
      of all six tumors, the immunohistochemical findings of five tumors (including the
      extrarenal tumor), and the ultrastructure of three tumors were analyzed. Clinical
      follow-up was obtained for all patients. RESULTS: Two tumors occurred in children
      and presented as large masses (> or = 15 cm), and 2 tumors were small (< 5 cm)
      and affected middle-aged adults; the remaining tumor, of intermediate size (6
      cm), occurred in an adolescent. One child with tuberous sclerosis also had a
      small (2 cm) extrarenal lesion. All tumors were circumscribed and had a red-brown
      cut surface. The largest tumors showed areas of hemorrhage and necrosis. The
      tumors were highly cellular and composed of various types of multinucleated and
      mononuclear cells. The most distinguishing of these, and virtually pathognomonic
      of this entity, were huge cells with abnormal strap-like and ameboid
      configurations having copious eosinophilic hyaline cytoplasm and myriad nuclei
      disposed peripherally in a ring-like fashion. Ganglion-like cells, polygonal
      cells, and spindle cells also were observed. For the most part, all cell types
      shared the same nuclear features, and except for one tumor, mitoses were
      negligible. The cells displayed a perivascular arrangement, and grew as loosely
      organized sheets oriented around abnormally dilated vascular channels or in a
      hemangiopericytic pattern; glomeruloid vessels were variably present. Notably,
      adipose tissue was inconspicuous. The tumors stained positive for HMB-45 protein,
      smooth muscle specific actin, and muscle specific actin antibodies, with a
      tendency for immunoreactivity to segregate along with individual cell phenotypes.
      Immunoperoxidase stains also disclosed a prominent and consistent intratumoral
      histiocytic component and a T-cell lymphoid infiltrate. Ultrastructurally, the
      tumor cells were replete with organelles showing highly electron-dense granules.
      All patients underwent radical nephrectomy; three patients with significant
      follow-up remain free of disease. CONCLUSIONS: AAML exhibits unusual but
      distinctive "pseudomalignant" histomorphologic features that facilitate its
      recognition, and a singular immunohistochemical profile that allows diagnostic
      confirmation. It occurs both sporadically and in association with tuberous
      sclerosis, affects both the adult and pediatric populations, and has shown an
      indolent behavior. AAML attests to the biologic and morphologic diversity that
      characterizes tuberous sclerosis hamartomata in general, and to the plasticity of
      the yet unclarified precursor of angiomyolipoma in particular.

PMID- 9781953
TI  - Neuroimaging and treatment implications of patients with multiple epidural spinal
      metastases.
AB  - BACKGROUND: Although multiple spinal epidural metastases (MEMs) commonly occur in
      cancer patients, their clinical significance remains uncertain. The authors
      attempted to ascertain the incidence of MEMs and their association with the
      completeness of spinal imaging by magnetic resonance (MR) scanning versus
      myelography to determine how often they are missed because of incomplete spinal
      imaging and to assess their prognostic and treatment implications. METHODS: A
      review of 337 epidural spinal cord compression (ESCC) cases seen at the Mayo
      Clinic between 1985 and 1993 was conducted. RESULTS: ESCC patients undergoing
      myelography only were significantly more likely to undergo complete spinal
      imaging (CSI)than patients undergoing either MR scan only or both imaging
      modalities (P < 0.0001). MEMs were detected in 32% of patients undergoing CSI and
      18% of patients with incomplete spinal imaging (P=0.02). Failure to image the
      cervical spine in patients with symptomatic thoracic or lumbar epidural lesions
      would have missed secondary epidural lesions in only 1% of patients; however,
      this figure increased to 21% for failure to image either the thoracic or
      lumbosacral spine when symptomatic disease was located elsewhere. Radiation
      oncologists included secondary epidural deposits in treatment ports in 93% of MEM
      cases. In a multivariate model, the presence of MEMs was an independent
      prognostic factor for poorer survival. CONCLUSION: The incidence of MEMs in
      patients with ESCC is approximately 30%, and their presence frequently alters
      treatment plans. It appears safe to forgo cervical spine MR scanning in patients
      with radiographically verified thoracic or lumbar ESCC; however, careful imaging
      of the thoracic and lumbar spine should be considered in all ESCC patients to
      detect MEMs.

PMID- 9781955
TI  - Pleural effusion in patients with non-Hodgkin's lymphoma: a case-controlled
      study.
AB  - BACKGROUND: Pleural effusion is reported in up to 20% of patients with non
      Hodgkin's lymphoma (NHL), most often at presentation. However, the prognostic
      implications of such findings are not clear. The majority of the information in
      the literature is based on minor observational studies or case reports.
      Therefore, a case-controlled study was performed to verify the clinical
      significance of pleural effusion in NHL. METHODS: Seventeen patients with pleural
      effusion at the time of presentation of NHL were identified. They were
      categorized by grade of NHL (based on the Working Formulation). Twenty-nine
      control patients with similar histopathologic characteristics who had Stage
      III/IV NHL without pleural effusion were matched to these cases by age, time of
      diagnosis, and treatment. RESULTS: Ten patients with intermediate grade NHL were
      matched with 23 controls. No statistically significant difference in complete
      remission or survival rates between these groups was found (P=0.69 and P=0.7,
      respectively). The remission and survival rates also were similar in the subgroup
      of patients and controls who were treated with aggressive chemotherapy.
      Similarly, no difference was found in these parameters between four cases and six
      matched controls with low grade lymphoma. No matched controls were found for the
      patients with high grade lymphoma, but these patients had an unfavorable outcome.
      Fourteen of the 17 studied patients had an exudative type of pleural effusion.
      Thoracentesis yielded a positive cytologic finding in every case. CONCLUSIONS:
      The presence of pleural effusion at the time of presentation of NHL does not
      adversely affect complete remission or survival rates.

PMID- 9781954
TI  - Outcome of peroneal neuropathies in patients with systemic malignant disease.
AB  - BACKGROUND: Peroneal neuropathies in patients with systemic cancer previously
      have been attributed to weight loss, but to the authors' knowledge other
      associated conditions have not been assessed, and the outcome of peroneal
      neuropathies in cancer patients has not been studied. METHODS: A retrospective
      chart review of patients evaluated at the Mayo Clinic between 1984 and 1993 with
      systemic malignant disease and a clinical diagnosis of peroneal neuropathy was
      performed to define factors associated with peroneal neuropathies and to assess
      outcome. All patients underwent neurologic examination and electromyography.
      RESULTS: Fifty-eight patients with systemic malignant disease were found to have
      a peroneal neuropathy. Peroneal neuropathies occurred more often in men (45
      patients) than in women (13 patients). The median age of the patients was 70
      years. The most common cancers were hematologic (12 patients) and pulmonary (11
      patients), followed by tumors of the prostate (8 patients), gastrointestinal
      tract (7 patients), transitional cell (5 patients), breast (5 patients), and
      colon (5 patients), as well as sarcomas and melanoma (5 patients). The median
      time to the diagnosis of peroneal neuropathy after the diagnosis of cancer was 5
      months. At the time of diagnosis, 34 patients had severe deficits, 19 had
      moderate deficits, and 5 had mild deficits. Associated factors included weight
      loss (occurring in 60% of patients), leg crossing (35% of patients), recent
      chemotherapy (16% of patients), cutaneous vasculitis (5% of patients), and local
      metastatic lesions (3% of patients). In nearly 50% of patients, peroneal
      neuropathy improved (25.9%) or resolved (22.4%). In 39.7% of patients, follow-up
      was inadequate because death occurred soon after diagnosis. Of the patients with
      adequate follow-up before death, 80% had either improvement (42.9%) or resolution
      (37.1%). CONCLUSIONS: For those patients with systemic malignant disease in whom
      peroneal neuropathy develops, the outcome of the neuropathy is good, with the
      majority of patients achieving partial or complete resolution.

PMID- 9781956
TI  - Treatment, patterns of failure, and survival of patients with Stage I nodal and
      extranodal non-Hodgkin's lymphomas, according to data in the population-based
      registry of the Comprehensive Cancer Centre West.
AB  - BACKGROUND: Primary extranodal lymphomas (EN-NHLs) are a heterogeneous category
      of tumors that are considered to be different from primary nodal non-Hodgkin's
      lymphomas (N-NHLs). To what extent these differences have clinical implications
      is currently not very clear, because knowledge of EN-NHL as a separate group is
      limited. METHODS: Using data from the Comprehensive Cancer Centre West (CCCW)
      population-based NHL registry in the Netherlands, N-NHL and EN-NHL patients were
      compared to determine differences in characteristics at diagnosis, responses to
      treatment, patterns of failure, and survival. RESULTS: At presentation, EN-NHL
      patients had poorer performance scores and more often bulky tumors compared with
      N-NHL patients, resulting in poorer responses to treatment (complete response
      rates were 72% and 84%, respectively; P=0.04) and inferior 5-year overall
      survival (49% and 63%, respectively; P=0.003). Among EN-NHL patients,
      considerable variations in response, survival, and relapse rates were observed,
      with gastric NHL patients having the best and central nervous system NHL patients
      having the worst prognosis (66% and 7% 5-year overall survival, respectively).
      Relapse rates for N-NHL and EN-NHL patients did not differ (39% and 36% 5-year
      relapse rates, respectively), whereas among EN-NHL patients considerable
      differences in relapse rates were noted. Relapses among N-NHL patients were
      mainly found in nodal sites, whereas recurrent disease in EN-NHL patients was
      mainly found in extranodal sites. CONCLUSIONS: In this population-based study,
      Stage I EN-NHL patients as a group had a poorer prognosis than N-NHL patients.
      However, among EN-NHL patients, considerable differences in response, relapse
      risk, and survival were observed. The failure analysis conducted in this study
      suggests that patterns of dissemination for N-NHL and EN-NHL are different.

PMID- 9781957
TI  - Evaluation of a patient file folder to improve the dissemination of written
      information materials for cancer patients.
AB  - BACKGROUND: Many cancer centers make available to patients written information
      material to supplement verbal information provided by clinicians. Randomized
      trials have demonstrated that providing such information can increase patient
      knowledge and satisfaction. However, little data are available regarding
      effective means of dissemination of such materials. The purpose of this study was
      to determine whether providing patients with a personal file folder after their
      first clinic appointment would improve the dissemination of written information
      materials and increase patient satisfaction. METHODS: A before/after study was
      performed. Consecutive patients with newly diagnosed cancer attending the
      Hamilton Regional Cancer Centre were selected randomly and interviewed by
      telephone within 1-2 weeks of the first clinic appointment regarding the number
      of information pamphlets received, patient satisfaction, and general preference
      for written information materials. The preintervention evaluation (T1) occurred
      over a 4-month period followed by the introduction of the personal file folder
      into the clinical practice. Six weeks after its introduction, the
      postintervention (T2) evaluation took place over the ensuing 4 months. RESULTS: A
      total of 300 patients completed the evaluation (150 each in T1 and T2).
      Responding patients in the two time periods were comparable with respect to
      background demographic variables. The mean number of information pamphlets
      received by patients increased with the introduction of the personal file folder
      from 2.4+/-2.0 standard deviations (SD) in T1 to 3.6+/-2.5 SD in T2 (P=0.0001).
      The percentage of patients planned for treatment who received treatment-related
      information increased from 36% (42 of 116 patients) in T1 to 65% (68 of 105
      patients) in T2 (P=0.002). Mean patient satisfaction increased from 3.3+/-1.1 SD
      to 3.8+/-1.0 SD over the 2 time periods (P=0.0001). The majority of patients
      (87%) believed it was important to receive written information materials.
      CONCLUSIONS: The patient file folder increased the dissemination of written
      information materials and currently is being incorporated into routine practice.

PMID- 9781959
TI  - Malignant vascular tumors in young patients.
AB  - BACKGROUND: To the authors' knowledge there are few published series of malignant
      vascular tumors in patients age < or = 21 years. METHODS: The authors
      retrospectively documented the clinical presentation, pathology, treatment, and
      outcome of patients age < or = 21 years with malignant vascular tumors treated
      between 1970-1995 at Memorial Sloan-Kettering Cancer Center. The histologic
      sections were rereviewed to confirm the diagnosis. RESULTS: Four patients were
      identified with angiosarcoma and two with malignant hemangioendothelioma. Five
      patients were female and one was male; the median age at diagnosis was 11.8 years
      (range, 8 months-21 years). The tumor involved the skin in one patient, soft
      tissue in one patient, bone in two patients, and internal organs in two patients.
      One patient had associated diffuse angiomatosis and another had the Klippel
      Trenaunay-Weber syndrome. This patient received prior radiation therapy to the
      primary site with the subsequent development of a vascular sarcoma. None of the
      patients had distant metastases at diagnosis. Resection was attempted in five
      patients and completed in four. Chemotherapy alone was given to three patients
      whereas radiation therapy alone and radiation plus chemotherapy were administered
      to one patient each. The median follow-up was 4.9 years (range, 1 month-12
      years). There were three deaths from progressive disease and two deaths from
      locoregional recurrences. Reexcision and radiotherapy controlled one local
      recurrence. Another patient developed recurrence to regional lymph nodes and
      further dissemination. The primary tumor in all three survivors was excised
      completely whereas two of the three patients who died of progressive disease
      underwent an incomplete excision or biopsy alone. CONCLUSIONS: Malignant vascular
      tumors are rare in the first two decades of life and when they do occur are very
      aggressive. Complete resection is curative for patients with localized lesions.

PMID- 9781958
TI  - Prognostic discrimination among neuroblastomas according to Ha-ras/trk A gene
      expression: a comparison of the profiles of neuroblastomas detected clinically
      and those detected through mass screening.
AB  - BACKGROUND: Neuroblastomas (NBs) exhibit a wide variety of clinical behavior. It
      is important to determine the biology of NB before treatment is instituted.
      METHODS: One hundred six NBs detected clinically (clinical NBs) were classified
      according to immunohistochemical expression of the Ha-ras and trk A genes.
      Association of the two-gene expression with patient outcome was examined
      retrospectively, and the possibility of prognostic prediction was evaluated. The
      profile of the expression of the two genes in 85 NBs detected through mass
      screening (mass NBs) was compared with that in clinical NBs. RESULTS: Ha-rasltrk
      A expression in clinical NBs was associated with disease free survival, even when
      the NBs had no amplification of the N-myc gene. Multivariate analysis
      demonstrated that the expression of Ha-rasl/trk A was a significant prognostic
      factor that was independent of stage, age at diagnosis, and N-myc amplification.
      Favorable outcomes of patients with advanced NB were distinguished by high Ha-ras
      and high trk A expression, and unfavorable outcomes were distinguished by low Ha
      ras and low trk A expression. A profile of the two genes in mass NBs was
      different from that in clinical NBs. Greater than 50% of the mass NBs were
      detected as localized tumors with high Ha-ras and high trk A expression. The mass
      screening detected NBs with favorable and unfavorable biology. CONCLUSIONS: The
      expression of Ha-ras and trk A is an excellent predictor of both favorable and
      unfavorable biology in NBs. The information it provides can be important in
      determining the appropriate therapeutic intervention for each patient.

PMID- 9781960
TI  - How well do medical oncologists' perceptions reflect their patients' reported
      physical and psychosocial problems? Data from a survey of five oncologists.
AB  - BACKGROUND: Modern cancer treatments can cure or prolong patients' lives.
      However, the associated physical and psychosocial problems can detrimentally
      affect patients' compliance with treatment and, ultimately, their outcomes.
      Therefore, oncologists need to recognize the problems experienced by their
      patients and, when possible, help resolve these problems. METHODS: The authors
      conducted a cross-sectional survey of physical symptoms, anxiety, depression, and
      perceived needs among 204 consenting patients visiting an outpatient medical
      oncology department. Immediately following consultations with consenting
      patients, medical oncologists and registrars also completed a survey in which
      they indicated their perception of each patient's level of each problem. These
      two data sets were then compared. RESULTS: Five oncologists' perceptions of
      patients' levels of the major physical symptoms cited in the survey (fatigue,
      nausea, vomiting, and hair loss) demonstrated the highest levels of awareness,
      with sensitivity rates up to 80%. Although sensitivity was less than 50% for all
      other physical symptoms, specificity was greater than 78% for all symptoms except
      fatigue. Only 17% of patients classified as clinically anxious and 6% of those
      classified as clinically depressed were perceived as such by their oncologists.
      However, the oncologists perceived much higher levels of perceived needs than
      patients reported, resulting in high sensitivity but low specificity rates.
      Oncologists' knowledge of and rapport with their patients and the pressure of
      their workloads were associated with their awareness of their patients' reported
      problems. CONCLUSIONS: Medical oncologists' perceptions may not accurately
      reflect their patients' reported physical and psychosocial experiences. Further
      interventions should be developed to assist oncologists in detecting such
      problems, especially psychosocial ones.

PMID- 9781961
TI  - Correlates of depressive symptomatology among adult daughter caregivers of a
      parent with cancer.
AB  - BACKGROUND: As a consequence of advances and changes in the detection and
      treatment of cancer, increasing demands are being placed on familial caregivers
      of elderly cancer patients. Understanding the factors that place familial
      caregivers at risk of poor psychological outcomes and threaten their ability to
      provide adequate care is important for maintaining chronically ill patients in
      the community. METHODS: Dyads comprised of 164 cancer outpatients (ages 60-90
      years) and their adult caregiving daughter completed structured telephone
      interviews. Hierarchical regression was used to determine the individual and
      cumulative effect of five domains of potential predictors on the daughters'
      depressive symptomatology (Center for Epidemiologic Studies Depression Scale [CES
      D]). RESULTS: The domains that were shown to be significantly predictive of a
      daughter's level of depressive symptomatology were daughter sociodemographics,
      constraints on/facilitators of caregiving, and caregiver burden. The domains of
      disease/patient characteristics and the daughter's appraisal of the caregiving
      situation were not found to be significant. The total model suggests that having
      a health-limiting condition, a greater sense of filial obligation, and greater
      caregiver burden were correlated with higher CES-D scores, whereas having
      graduated college, having other social roles, having favorable attitudes
      regarding her caregiving experience, and providing care in a greater number of
      domains of care were correlated with lower scores. CONCLUSIONS: These findings
      demonstrate the importance of focusing on situational factors that may function
      to constrain or facilitate caregiving when investigating caregiver depression.

PMID- 9781962
TI  - The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a
      summary of 84,836 cases from the past decade. The American College of Surgeons
      Commission on Cancer and the American Cancer Society.
AB  - BACKGROUND: This study reviews the case-mix characteristics, management, and
      outcomes of melanoma cases occuring in the U.S. within the last decade. METHODS:
      Analyses of the National Cancer Data Base (NCDB) were performed on cases
      diagnosed between 1985 through 1994. A total of 84,836 cases comprised of
      cutaneous and noncutaneous melanomas were evaluated. RESULTS: The percentages of
      melanomas that were cutaneous, ocular, mucosal, and unknown primaries were 91.2%,
      5.2%, 1.3%, and 2.2%, respectively. For cutaneous melanomas, the proportion of
      patients presenting with American Joint Committee on Cancer Stages 0, I, II, III,
      and IV were 14.9%, 47.7%, 23.1%, 8.9%, and 5.3%, respectively. Factors associated
      with decreased survival included more advanced stage at diagnosis, nodular or
      acral lentiginous histology, increased age, male gender, nonwhite race, and lower
      income. Multivariate analysis identified stage, histology, gender, age, and
      income as independent prognostic factors. For ocular melanomas, 85.0% were uveal,
      4.8% were conjunctival, and 10.2% occurred at other sites. During the study
      period, there was a large increase in the proportion of ocular melanoma patients
      treated with radiation therapy alone. For mucosal melanomas, the distribution of
      head and neck, female genital tract, anal/rectal, and urinary tract sites was
      55.4%, 18.0%, 23.8%, and 2.8%, respectively. Patients with lymph node involvement
      had a poor prognosis. For unknown primary melanomas, the distribution of
      metastases as localized to a region or multiple sites at presentation was 43.0%
      and 57.0%, respectively. Surgical treatment of patients with unknown primary site
      of the melanoma resulted in better survival compared with no treatment.
      CONCLUSIONS: Treatment of early stage cutaneous melanoma resulted in excellent
      patient outcomes. In addition to conventional prognostic factors, socioeconomic
      factors were found to be associated with survival.

PMID- 9781963
TI  - The National Cancer Data Base report on prostate carcinoma after the peak in
      incidence rates in the U.S. The American College of Surgeons Commission on Cancer
      and the American Cancer Society.
AB  - BACKGROUND: Prostate carcinoma incidence has been declining since 1992 after a
      period of marked increase. Recent data from the National Cancer Data Base (NCDB)
      were examined to assess changes in prostate carcinoma patient characteristics and
      disease and treatment patterns coincidental to this decline. The NCDB is a
      program of the American College of Surgeons Commission on Cancer and the American
      Cancer Society that collects timely data from institutions representing every
      level of cancer care. METHODS: Data from 1114 hospitals regarding 103,979
      patients diagnosed with prostate carcinoma in 1992 and from 1144 hospitals
      regarding 72,337 patients diagnosed in 1995 were studied. Patient and disease
      characteristics studied included age, race, American Joint Committee on Cancer
      stage, and tumor histologic grade. Trends in treatment and variations in
      treatment by region also were examined. RESULTS: The average age at diagnosis
      declined by 2 years over the period studied and the proportion of patients
      identified as African-American increased from 8.8% to 11.8%. The proportion of
      patients diagnosed with localized disease and the proportion of tumors of
      moderately differentiated histologic grade increased. The overall proportion of
      patients treated by radical prostatectomy increased and the use of external beam
      radiation treatment decreased. Substantial regional variation in treatment
      patterns was observed. The Pacific and Mountain state regions of the U. S. had
      the highest proportions of patients treated by radical prostatectomy although
      increases were occurring in other regions. Use of external beam radiation
      treatment was highest in the Northeast and Southeast states and was declining in
      the majority of regions. Use of brachytherapy radiation treatment by implantation
      of radioactive seeds was infrequent but increasing. CONCLUSIONS: Comparison of
      the basic characteristics of prostate carcinoma data from 1992 and 1995 shows
      that patients are being diagnosed at younger ages and earlier stages, the
      proportion of African-Americans has increased, and more patients are being
      treated for cure. Regional differences in patterns of care persist but may be
      moderating. The annual prostate carcinoma death rate in the U.S. has declined an
      average of 1% per year since 1990.

PMID- 9781964
TI  - Intracoronary aspiration thrombectomy for acute myocardial infarction.
AB  - To investigate the pathogenesis of acute myocardial infarction (AMI) and values
      of intracoronary aspiration thrombectomy (ICAT), we applied ICAT to reperfusion
      therapy using generally available intracoronary catheters to aspirate
      intracoronary occlusive tissues. We assigned ICAT or primary percutaneous
      transluminal coronary angioplasty (PTCA) to patients with evolving AMI
      (Thrombolysis In Myocardial Infarction (TIMI) trial grade 0), and investigated
      primary histopathologic, clinical, and angiographic outcomes in 43 patients
      treated with ICAT alone or followed by PTCA, and compared the outcomes with those
      in 48 patients treated with primary PTCA. No major complications (procedural
      death, emergent bypass graft surgery) occurred. Reconalization (TIMI grade 3 and
      2) was achieved in 25 patients (58%) with ICAT alone and in 39 patients (91%)
      with ICAT alone or followed by PTCA. Aspirated thrombi were defined as recent
      thrombi in 21 cases (49%), atheroma in 6 (14%), no thrombi in 13 (30%), and
      organized thrombi in 1 case. In cases of recent thrombi, ICAT alone provided
      recanalization more frequently than in those of atheroma or no thrombi (18 of 21
      [86%], 3 of 6 [50%], 4 of 13 [31%], respectively; p < 0.05; recent thrombi vs
      atheroma or no thrombi). There were no significant differences in primary
      recanalization rate (ICAT alone or followed by PTCA vs primary PTCA; 91% vs 92%)
      or incidence of complications between the 2 strategies. These results indicate
      that although the pathogenesis of AMI is heterogeneous in each individual case,
      intracoronary thrombus contributes little to the pathogenesis of average AMI, and
      therefore mechanical approaches may be feasible to maximize reperfusion therapies
      for AMI.

PMID- 9781965
TI  - Comparison of the prognostic value of C-reactive protein and troponin I in
      patients with unstable angina pectoris.
AB  - This study assessed the prognostic value of cardiac troponin I (cTnI) and C
      reactive protein (CRP) in unstable angina, and specifically in patients with
      angiographically proven coronary artery disease. These biochemical parameters,
      which are related to myocardial injury or to systemic inflammation, may help in
      short-term risk stratification of unstable angina. We prospectively studied 195
      patients with unstable angina, 100 of whom had angiographically proven coronary
      artery disease (with normal creatine kinase [CK] and CK-MB mass). Serum
      concentrations of cTnI (N < 0.4 ng/ml) and CRP (N < 3 mg/L) were measured at
      admission, 12, and 24 hours later. The rate of in-hospital major adverse cardiac
      events (death, myocardial infarction, or emergency revascularization) was higher
      in patients with increased cTnI within the first 24 hours, regardless of the
      results of coronary angiography (23% vs 7%; p < 0.001). Conversely, events
      occurred at similar rates in patients with or without increased CRP. In patients
      with angiographic evidence of coronary artery disease, multivariate analysis
      showed that increased cTnI within 24 hours of admission (35 patients) was an
      independent predictor of major adverse cardiac events (odds ratio 6.7, range 1.7
      to 27.3), but not cTnI levels at admission and CRP at 0, 12, and 24 hours. Thus,
      both in unselected patients with unstable angina and in patients with
      angiographically proven coronary artery disease, increased cTnI within 24 hours
      of admission, but not CRP, is a predictor of in-hospital clinical outcome. We
      also found a temporal link between cTnI increase and late elevation of CRP,
      suggesting that systemic inflammation may partially be a consequence of
      myocardial injury.

PMID- 9781966
TI  - Depression and the risk of coronary heart disease in the Normative Aging Study.
AB  - Increasing evidence supports an association between symptomatic depression and
      the risk of coronary heart disease (CHD), although no single study has compared
      multiple depression scales. We hypothesized that higher levels of symptomatic
      depression assessed from different depression scales were associated with the
      risk of CHD. We examined this relation in the Normative Aging Study, a
      prospective cohort of older men. A total of 1,305 men free of diagnosed CHD in
      1986 completed the revised Minnesota Multiphasic Personality Inventory (MMPI-2).
      We categorized scores for the MMPI-2 D, MMPI-2 DEP, and Symptom Checklist-90 (SCL
      90) depression scales. During an average 7.0 years of follow-up, 110 cases of
      incident CHD occurred, including 30 cases of nonfatal myocardial infarction, 20
      cases of fatal CHD, and 60 cases of angina pectoris. Compared with men reporting
      the lowest level of depression, men in the highest level of depression had
      multivariate-adjusted relative risks of incident CHD (total CHD and angina) of
      1.46 (95% confidence interval 0.83 to 2.57), 2.07 (95% confidence interval 1.13
      to 3.81), and 1.73 (95% confidence interval 0.97 to 3.10) for the MMPI-2 D, MMPI
      2 DEP, and SCL-90 scales, respectively. Similar RRs were obtained for each CHD
      subtype according to each depression scale. We found strong dose-response
      relations between level of depression measured by the MMPI-2 DEP scale and
      incidence of both angina pectoris (p value for trend, 0.039) and CHD (p value for
      trend, 0.016). Among older men, symptomatic depression measured by any of 3
      depression scales may be positively associated with the risk of CHD.

PMID- 9781967
TI  - Accuracy of single-photon emission computed tomography myocardial perfusion
      imaging in patients with stents in native coronary arteries.
AB  - Strategies to noninvasively evaluate patients after coronary stenting have not
      been evaluated. To determine the accuracy of single-photon emission computed
      tomography (SPECT) myocardial perfusion imaging in patients after coronary
      stenting, 209 patients who had undergone stenting followed by late stress SPECT
      myocardial perfusion imaging were evaluated. Quantitative coronary angiography
      was performed in 33 patients following SPECT imaging. SPECT restenosis was
      defined as a reversible or fixed defect within the stented vascular territory.
      Angiographic restenosis was examined using 2 definitions: total area narrowing >
      or =50% or > or =70% of the stent site or stented artery. The SPECT and
      angiographic findings were concordant in 22 of 33 stented vascular territories
      using the 50% definition of restenosis and in 29 of 33 stented territories using
      the 70% definition. Use of the 70% definition of restenosis resulted in improved
      accuracy of SPECT to detect a significant stenosis in the stented artery.
      Sensitivity, specificity, positive predictive value, negative predictive value,
      and accuracy of SPECT were 95%, 73%, 88%, 89%, and 88% respectively. In patients
      with positive SPECT scans, the most significant stenosis in the stented artery
      was outside the stent site in 50% of cases. SPECT imaging appears to be accurate
      to predict significant stenosis in the stented artery, although the most severe
      stenosis is frequently distant from the stent site.

PMID- 9781968
TI  - Impaired baroreflex sensitivity and sympathovagal balance in syndrome X.
AB  - Alterations of autonomic nervous control of cardiac function have been described
      in syndrome X. The characteristics, however, of the autonomic control of the
      cardiovascular system in patients with syndrome X have not been adequately
      studied; thus, the aim of the present study was to investigate the role of
      baroreceptor sensitivity and sympathovagal balance in syndrome X. The study group
      included 12 patients with syndrome X, 12 age- and sex-matched control patients
      with coronary artery disease, and 12 age- and sex-matched controls with no
      evidence of heart disease. Baroreceptor sensitivity was evaluated by calculating
      the regression line relating phenylephrine-induced increases in systolic blood
      pressure to the attendant changes in the RR interval. Sympathovagal balance was
      assessed by using heart rate variability in the time and frequency domain and
      measuring plasma norepinephrine at rest and during incremental bicycle exercise.
      Baroreceptor sensitivity was significantly reduced in syndrome X compared with
      that in control normal subjects (7.4 +/- 1.2 vs 16.8 +/- 2.3 ms/mm Hg; p < 0.02).
      This was associated with a significantly lower percentage of adjacent normal RR
      intervals that differ by >50 ms, lower root-mean-square of the difference of
      adjacent RR intervals, and lower logarithmic value of the high-frequency
      component in patients with syndrome X compared with normal subjects. A
      nonsignificant trend toward lower baroreceptor sensitivity was found in patients
      with syndrome X compared with control ischemic patients (7.4 +/- 2 vs 12.2 +/-
      1.3 ms/mm Hg). A nonsignificant trend toward a higher value of the low- to high
      frequency ratio was also observed in patients with syndrome X than in both
      control groups. No difference was detected in norepinephrine levels either at
      rest or during exercise or in the exercise-induced norepinephrine increase
      between the 3 groups. No difference was also observed between ischemic patients
      and normal subjects in either baroreceptor sensitivity or heart rate variability
      measurements. A significant correlation (r = 0.80, p < 0.01) was found between
      baroreceptor sensitivity and the high-frequency component in normal controls but
      not for other measurements of autonomic function in the 3 groups. In conclusion,
      patients with syndrome X have an altered autonomic control of the cardiovascular
      system characterized by impaired baroreceptor sensitivity and reduced heart rate
      variability. Abnormal autonomic regulation of the cardiovascular system may be of
      pathophysiologic importance in syndrome X.

PMID- 9781969
TI  - Power spectral analysis of heart period variability of preceding sinus rhythm
      before initiation of paroxysmal atrial fibrillation.
AB  - Time domain analysis of heart period variability in patients without structural
      heart disease demonstrated increased parasympathetic modulation before paroxysmal
      atrial fibrillation (AF) occurring predominantly at night. However, diurnal
      differences in autonomic activity preceding AF episodes in a diverse patient
      population have not been assessed. Accordingly, we performed spectral analysis of
      heart period variability on Holter recordings during sinus rhythm preceding AF in
      29 patients, 17 with night and 12 with day episodes. Samples taken 5, 10, and 20
      minutes before AF onset were compared. Normalized high-frequency (HF) spectral
      power change was greater when comparing the interval 10 to 5 minutes with 20 to
      10 minutes preceding AF in 26 of 29 patients (0.09 +/- 0.07 vs 0.03 +/- 0.02; p <
      0.0001). HF spectral power increased before 3 of 12 AF episodes during the day
      compared with 15 of 17 AF episodes during the night (p = 0.001). Nocturnal AF
      episodes were preceded by increased HF spectral power in the 5- versus the 20
      minute sample expressed as natural logarithm-transformed values (5.6 +/- 4.8 vs
      4.2 +/- 4.0; p < 0.005) and normalized values (0.19 +/- 0.09 vs 0.10 +/- 0.07; p
      < 0.02), a decrease in low-frequency/HF ratio (1.05 +/- 0.61 vs 2.21 +/- 1.75; p
      < 0.05) and heart rate (60 +/- 13 vs 71 +/- 13 beats/min; p = 0.06). Structural
      heart disease was more common with daytime than nocturnal AF episodes (58% vs
      18%, p < 0.05). In conclusion, HF spectral power change was increased preceding
      most AF episodes. However, diurnal differences were demonstrated. Contrary to
      daytime AF, increased parasympathetic activity preceded predominantly nocturnal
      AF, mostly in younger patients with structurally normal hearts.

PMID- 9781970
TI  - Comparison of results in two implantable defibrillators. Jewel 7219D
      Investigators.
AB  - The Jewel 7219D was the first non-thoracotomy implantable cardioverter
      defibrillator (ICD) with biphasic shock capability small enough to be placed in
      the prepectoral subcutaneous position. Size reduction of ICDs is desirable, but
      safety and efficacy of smaller devices must be demonstrated. Outcomes of patients
      treated with the Jewel 7219D defibrillator (n = 1,781) and with its precursor
      model PCD 7217B (n = 2,637) were compared. To use PCD patients (n = 2,637) as
      historical (n = 2,574) and concurrent controls (n = 63), statistical adjustments
      using the Cox proportional-hazards regression model were made. Jewel recipients
      (n = 1,781) treated in 106 US and 32 non-US centers exhibited similar
      characteristics including a mean age of 59 years, 78% men, ejection fraction of
      34%, history of aborted sudden cardiac death in 41%, and coronary artery disease
      in 70%. Implantation was completed in 1,777 of 1,781 (99.9%) attempts and success
      with the first electrode configuration and polarity was 89.5%. Kaplan-Meier
      cumulative first-year survivals for cardiac and all-cause mortality were 98.5%
      and 93.3%. Complication-free first-year survival for Jewel implants in
      prepectoral subcutaneous (n = 582), subpectoral submuscular (n = 366), and
      abdominal (n = 449) positions did not differ (p > 0.05). First-year survival free
      of pocket-related complications exceeded 98% in all locations. Adjusted cardiac
      and all-cause first-year mortality, and efficacy in terminating spontaneous
      tachyarrhythmias did not differ between the 2 device groups. In conclusion, the
      safety and efficacy of Jewel model 7219D in the prepectoral subcutaneous position
      are at least equal to either those of Jewel models implanted in different
      positions or to those of the previously extensively characterized PCD 7217B.

PMID- 9781971
TI  - Effect of amlodipine on mode of death among patients with advanced heart failure
      in the PRAISE trial. Prospective Randomized Amlodipine Survival Evaluation.
AB  - Investigations of calcium antagonists in patients with advanced heart failure
      have raised concern over an increased risk of worsening heart failure and heart
      failure deaths. We assessed the effect of amlodipine on cause-specific mortality
      in such patients enrolled in a randomized, double-blind, placebo-controlled
      trial. In total, 1,153 patients in New York Heart Association class IIIb or IV
      heart failure were randomized to receive amlodipine or placebo, along with
      angiotensin-converting enzyme inhibitors, diuretics, and digitalis. Over a median
      14.5 months of follow-up, 413 patients died. Cardiovascular deaths accounted for
      89% of fatalities, 50% of which were sudden deaths and 45% of which were due to
      pump failure, with fewer attributed to myocardial infarction (3.3%) or other
      cardiovascular causes (1.6%). Amlodipine treatment resulted in a greater relative
      reduction in sudden deaths (21%) than in pump failure deaths (6.6%) overall. When
      patients were classified by etiology of heart failure (ischemic or nonischemic),
      cause-specific mortality did not differ significantly between treatment groups in
      the ischemic stratum. In the nonischemic stratum, however, sudden deaths and pump
      failure deaths were reduced by 38% and 45%, respectively, with amlodipine. Thus,
      when added to digitalis, diuretics, and angiotensin-converting enzyme inhibitors
      in patients with advanced heart failure, amlodipine appears to have no effect on
      cause-specific mortality in ischemic cardiomyopathy, but both pump failure and
      sudden deaths appear to be decreased in nonischemic heart failure patients
      treated with amlodipine.

PMID- 9781972
TI  - Undetected cardiogenic shock in patients with congestive heart failure presenting
      to the emergency department.
AB  - The purpose of this study was to examine the use of lactic acid levels and
      continuous central venous oxygen saturation (central venous oximetry) to stratify
      and treat patients with acutely decompensated end-stage chronic congestive heart
      failure (CHF) presenting to the emergency department. This prospective,
      convenience, non-outcome study was performed at an urban tertiary care hospital.
      Patients with end-stage CHF with an ejection fraction <30% presenting in
      decompensated CHF were eligible for the study. Patients were assessed using the
      Killip classification and New York Heart Association criteria. After lactic acid
      levels were obtained, patients were managed according to a standardized protocol
      guided by central venous oximetry. The patients were divided into high lactic
      acid (n = 22), low lactic acid (n = 5), and control groups (stable patients
      presenting to a cardiology clinic, n = 17) for comparison. There was no
      statistical difference in vital signs, or Killip and New York Heart Association
      criteria among the 3 groups. Central venous oxygen saturation was significantly
      lower in the high lactic acid group (32 +/- 12%) than in the normal lactic acid
      (51 +/- 13%) and control groups (60 +/- 6%) (p < 0.001). After treatment there
      was a significant decrease in lactic acid (-3.65 +/- 3.65 mM/L) and an increase
      in central venous oxygen saturation (32 +/- 13%) in the high lactic acid group
      compared with the normal lactic acid group (p < 0.001). A significant subset of
      patients with decompensated end-stage CHF present to the emergency department in
      occult shock and are clinically indistinguishable from patients with mildly
      decompensated CHF and stable CHF. Once identified, these patients require
      aggressive alternative management and disposition. Further study is necessary to
      identify whether this intervention impacts morbidity, mortality, and health care
      resource consumption.

PMID- 9781973
TI  - Analysis of risk factors for development of atrial fibrillation early after
      cardiac valvular surgery.
AB  - Atrial fibrillation (AF) commonly develops after cardiac valvular surgery. The
      objective of this study was to identify risk factors for postoperative AF
      following valvular surgery. A cohort of 915 consecutive adult patients undergoing
      isolated valvular surgery with preoperative sinus rhythm was analyzed. Univariate
      and independent multivariate risk factors for postoperative AF were determined. A
      second cohort of 305 patients with the same inclusion criteria was used to
      validate the multivariate predictors. Patients studied had a mean age of 56.1 +/-
      14.7 years, 57.9% were men, 79.6% had a normal left ventricular ejection
      fraction, and their mean left atrial size was 46.2 +/- 9.3 mm. The incidence of
      postoperative AF was 36.7%. Independent predictors of postoperative AF included:
      advanced age (odds ratio [OR] 1.506 per decade, 95% confidence interval, [CI]
      1.35 to 1.68, p = 0.0001); mitral stenosis (OR 2.066, CI 1.21 to 3.52, p =
      0.0077); left atrial enlargement (OR 1.468, CI 1.07 to 2.01, p = 0.0165); use of
      systemic hypothermia (OR 0.572, CI 0.422 to 0.776, p = 0.0003); and a history of
      cardiac surgery (OR 0.676, CI 0.465 to 0.981, p = 0.0393). Among these variables,
      advanced age, mitral stenosis, and left atrial enlargement were confirmed as
      independent risk factors in the validation cohort.

PMID- 9781974
TI  - Coronary thrombosis during acute myocardial infarction: Roberts was right!
AB  - Pathologic studies have varied with clinical belief regarding the role of acute
      thrombotic occlusion as the inciting event during myocardial infarction.
      Aspiration thrombectomy, by employing a new catheter, has been performed during
      myocardial infarction and confirms the pathologic findings that intracoronary
      thrombus is absent in a substantial number of patients with acute myocardial
      infarction.

PMID- 9781975
TI  - Effects of trimetazidine on ischemic left ventricular dysfunction in patients
      with coronary artery disease.
AB  - We studied 15 patients with chronic coronary artery disease (13 men aged 62 +/- 8
      years) undergoing dobutamine (5 to 40 microg/kg/min) echocardiography at the end
      of two 15-day treatment periods with placebo and trimetazidine (20 mg 3 times
      daily) given in random order, according to a double-blind, crossover design.
      Results show that trimetazidine improves resting left ventricular function and
      reduces the severity of dobutamine-induced ischemic myocardial dysfunction.

PMID- 9781976
TI  - Risk factors for new coronary events in older African-American men and women.
AB  - Independent risk factors for new coronary events in older African-American men
      were (1) age (risk ratio = 1.037), (2) cigarette smoking (risk ratio = 2.231),
      (3) hypertension (risk ratio = 2.531), (4) serum total cholesterol (risk ratio =
      1.012), (5) serum high-density lipoprotein (HDL) cholesterol (inverse
      association) (risk ratio = 0.948), and (6) prior coronary artery disease (CAD)
      (risk ratio = 2.288). Independent risk factors for new coronary events in older
      African-American women were (1) cigarette smoking (risk ratio = 2.202), (2)
      hypertension (risk ratio = 2.344), (3) diabetes mellitus (risk ratio = 1.632),
      (4) serum total cholesterol (risk ratio = 1.008), (5) serum HDL cholesterol
      (inverse association) (risk ratio = 0.936), (6) age (risk ratio = 1.026), and (7)
      prior CAD (risk ratio = 2.368).

PMID- 9781978
TI  - Usefulness of extracorporeal membrane oxygenation for treatment of fulminant
      myocarditis and circulatory collapse.
AB  - Prognosis for fulminant myocarditis with cardiogenic shock refractory to
      conventional therapy is poor. This report describes mechanical circulatory
      support with extracorporeal membrane oxygenation as an effective alternative for
      treating fulminant myocarditis with circulatory collapse.

PMID- 9781977
TI  - Reproducibility of cardiopulmonary exercise testing in elderly patients with
      congestive heart failure.
AB  - Elderly patients with congestive heart failure, including those with preserved
      systolic function, underwent maximal cardiopulmonary exercise testing. Maximal
      exercise oxygen consumption, exercise time, heart rate, respiratory exchange
      ratio, and ventilatory anaerobic threshold showed good reproducibility.

PMID- 9781979
TI  - Left ventricular morphology in elite female resistance-trained athletes.
AB  - Long-term resistance training as performed by elite female resistance-trained
      athletes appears to be an insufficient stimulus to alter left ventricular cavity
      size, wall thickness, or estimated mass.

PMID- 9781980
TI  - A noninvasive method for estimating cardiac output using lung to finger
      circulation time of oxygen.
AB  - To develop a safe, noninvasive, simple, inexpensive, and clinically adaptable
      method for estimating cardiac output, we evaluated the potential of lung to
      finger circulation time (LFCT) and buildup time (Tb) of oxygen as measured by
      pulse oximetry to estimate cardiac output. Significant correlation was found
      between cardiac output as measured by thermodilution and the inverse of LFCT (R =
      0.76, p < 0.001, SEE = 0.9 L/min) as well as the inverse of Tb (R = 0.72, p <
      0.001, SEE = 0.9 L/min).

PMID- 9781981
TI  - On correcting plasma cholesterol levels and preventing the clinical sequelae of
      atherosclerotic coronary heart disease.

PMID- 9781982
TI  - Ethics of cochlear implantation in young children: a review and reply from a Deaf
      World perspective.
AB  - This article examines ethical dilemmas related to cochlear implant surgery in
      children. These dilemmas arise from the existence of a linguistic and cultural
      minority called the Deaf World. Organizations of culturally Deaf adults in the
      United States and abroad, as well as the World Federation of the Deaf, have, on
      ethical grounds, strongly criticized the practice of cochlear implant surgery in
      children. Three ethical dilemmas are examined. (1) The surgery is of unproven
      value for the main significant benefit sought, language acquisition, whereas the
      psychological, social, and linguistic risks have not been assessed. Thus the
      surgery appears to be innovative, but innovative surgery on children is ethically
      problematic. (2) It is now widely recognized that the signed languages of the
      world are full-fledged natural languages, and the communities that speak those
      languages have distinct social organizations and cultures. Deaf culture values
      lead to a different assessment of pediatric cochlear implant surgery than do
      mainstream (hearing) values, and both sets of values have standing. (3) The
      fields of otology and audiology want to provide cochlear implants to Deaf
      children but also, their leaders say, want to protect Deaf culture; those appear
      to be conflicting goals in principle because, if there were perfect implants, the
      ranks of the Deaf World would diminish.

PMID- 9781983
TI  - Age- and gender-related elastin distribution changes in human vocal folds.
AB  - The composition of the lamina propria in human vocal folds has been shown to
      affect vocal performance. Elastin plays a significant role in the biomechanical
      effects of the lamina propria. We obtained 19 larynges from the state medical
      examiner from subjects whose cause of death was unrelated to the trachea and
      laryngeal regions. The sample contained male and female subjects in the infant,
      adult, and geriatric age groups. We stained the vocal folds for elastin with
      Verhoeff's elastic tissue stain and studied them with use of an image analysis
      system configured for light microscopy. Distributions of elastin were measured
      from superficial to deep within the lamina propria (from epithelium to vocal
      muscle). These elastin distributions were then compared with the use of
      statistical software. The data showed that there was an increase in elastin
      content from the infant through geriatric stages. No gender-related differences
      were found. Infant folds had about 23% of the elastin found in adults, and
      geriatric subjects had about 879% of the elastin found in adults. Both of these
      results were statistically significant (p < 0.05). The distributions were
      consistent with previous observations that the lamina propria is a layered
      structure with most of the elastin present in the intermediate layer. This layer
      was larger in geriatric subjects than in adult and pediatric subjects. We
      observed that the fiber diameter appeared to be larger in geriatric subjects
      (this observation is currently being verified with electron microscopy) whereas
      smaller, spiraled fibers appeared in pediatric subjects.

PMID- 9781984
TI  - Sodium nitroprusside/nitric oxide causes apoptosis in spiral ganglion cells.
AB  - OBJECTIVE: In the cochlea, excitatory amino acid receptor overstimulation induces
      toxicity in spiral ganglion neurons by an unknown mechanism. In the central
      nervous system, excitatory amino acid-induced toxicity is mediated by nitric
      oxide, which induces apoptosis in neurons. This study tested the hypothesis that
      cochlear nitric oxide-mediated toxicity is the result of induction of apoptosis
      in spiral ganglion neurons. METHODS: The cochleas of 15 gerbils randomly assigned
      to different groups were perfused for 30 minutes with a test solution of 1 mmol/L
      sodium nitroprusside, a nitric oxide donor, or a control solution of artificial
      perilymph. Animals were killed at varying times, including 2, 3, 4, 8, and 18
      hours after perfusion. DNA fragmentation or in situ terminal deoxynucleotidyl
      transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling analysis
      was done on cochleas for detection of apoptosis. RESULTS: Analysis by both
      techniques demonstrated marked apoptotic cell changes in spiral ganglion neurons
      of sodium nitroprusside-treated cochleas evident 4 to 8 hours after perfusion, as
      compared with minimal to no evidence of apoptosis in spiral ganglion neurons of
      control specimens. CONCLUSIONS: Exposure to high levels of nitric oxide induces
      apoptosis in spiral ganglion neurons. Because apoptosis is a delayed, potentially
      reversible cell death pathway, this may present an opportunity for intervention
      to prevent or attenuate hearing damage induced by excitotoxic stimuli.

PMID- 9781985
TI  - Tumor reduction in vivo after adenoviral mediated gene transfer of the herpes
      simplex virus thymidine kinase gene and ganciclovir treatment in human head and
      neck squamous cell carcinoma.
AB  - Gene transfer offers the possibility of novel therapies for head and neck
      squamous cell carcinoma (HNSCC). To this end, we demonstrate that a replication
      deficient adenovirus vector (Ad.RSVlacZ) can efficiently transduce foreign genes
      into human HNSCC cell lines in vitro, and that adenoviral mediated transfer of
      herpes simplex virus thymidine kinase (Ad.RSVtk) followed by exposure to
      ganciclovir results in tumor cell killing in vitro and in vivo. Exposure to
      Ad.RSVlacZ resulted in lacZ expression at multiplicities of infection (MOIs) of
      10 and 100 for the cell lines HEp-2 and FaDu, respectively. This increased to 97%
      (HEp-2) and 49% (FaDu) at an MOI of 10,000. For HEp-2, maximum expression
      occurred during the first 48 hours after exposure (52% at 24 hours, 48% at 48
      hours; MOI 500), then declined by 40% per day. This rapid decline may be caused
      by dilution of the gene through cell proliferation, because normalizing for the
      increase in total protein shows that the total number of cells expressing lacZ is
      stable from days 1 to 4. FaDu and HEp-2 were then transduced by AD.RSVtk and
      exposed to 20 microM ganciclovir for 24 hours. Significant tumor cell killing, as
      measured by a colony forming assay, occurred at an MOI of 2 for HEp-2 and 20 for
      FaDu. At an MOI of 200, 100% of HEp-2 and 97% of FaDu cells were killed. Next,
      subcutaneous tumor nodules derived from FaDu and HEp-2 were established in the
      flanks of SCID mice. Direct intratumoral injection of Ad.RSVtk followed by 7 days
      of ganciclovir therapy resulted in an adenovirus dose dependent reduction of
      tumor growth, and an actual size reduction of established tumor nodules at the
      highest does (10(10) plaque forming units). In conclusion, an adenovirus vector
      can efficiently transduce HNSCC cell lines in vitro. Maximum marker gene
      expression occurred during the first 48 hours after transduction. Transduction by
      Ad.RSVtk followed by exposure to ganciclovir resulted in tumor cell killing in
      vitro and in vivo.

PMID- 9781986
TI  - End-to-side neurorraphy: a long-term study of neural regeneration in a rat model.
AB  - This study evaluated long-term reinnervation of an end-to-side neurorraphy and
      the resultant functional recovery in a rat model. The divided distal posterior
      tibial nerve was repaired to the side of an intact peroneal nerve. Control groups
      included a cut-and-repair of the posterior tibial nerve and an end-to-end repair
      of the peroneal nerve to the posterior tibial nerve. Evaluations included walking
      track analysis, nerve conduction studies, muscle mass measurements, retrograde
      nerve tracing, and histologic evaluation. Walking tracks indicated poor recovery
      of posterior tibial nerve function in the experimental group. No significant
      difference in nerve conduction velocities was seen between the experimental and
      control groups. Gastrocnemius muscle mass measurements revealed no functional
      recovery in the experimental group. Similarly, retrograde nerve tracing revealed
      minimal motor neuron staining in the experimental group. However, some sensory
      staining was seen within the dorsal root ganglia of the end-to-side group.
      Histologic study revealed minimal myelinated axonal regeneration in the
      experimental group as compared with findings in the other groups. These results
      suggest that predominantly sensory regeneration occurs in an end-to-side
      neurorraphy at an end point of 6 months.

PMID- 9781987
TI  - Early-response cytokine expression in adult middle ear effusions.
AB  - Various cytokines are presently known to be associated with the regulation of
      inflammatory responses. In pediatric otitis media, cytokines that correlate with
      various degrees of inflammation are present in middle ear effusions as
      inflammatory mediators. The present study was undertaken to examine the potential
      role of the early-response cytokines, interleukin-1beta and tumor necrosis factor
      alpha, in adult otitis media. Fifty-nine adults with otitis media underwent
      tympanocentesis, and the effusion specimens were analyzed for the presence of
      both cytokines by enzyme-linked immunosorbent assay methods. Eighty-eight percent
      of the effusions were serous in nature. Sixty-seven percent of the patients had a
      known history of head and neck malignancy and radiation to the temporal bone.
      Twelve percent of the effusions were positive for interleukin-1beta expression,
      compared with 85% of effusions in children with otitis media. Eight percent of
      the effusions contained tumor necrosis factor-alpha, compared with 85% of those
      collected in pediatric otitis media. All of the specimens that contained tumor
      necrosis factor-alpha also contained interleukin-1beta. In the present study,
      there was no correlation with head and neck malignancy/radiation or the clinical
      degree of inflammation with the presence of either cytokine. We conclude that
      adult otitis media is associated with lower expression of an acute inflammatory
      response, as judged by the levels of interleukin-1beta and tumor necrosis factor
      alpha in the effusions. Additionally, adult otitis probably represents a less
      severe and more chronic inflammatory state in comparison with pediatric otitis
      media. Further analysis of inflammatory mediators in adult otitis media is
      necessary to evaluate the contribution of cytokines in relation to various
      etiologic factors.

PMID- 9781988
TI  - Analysis of protease activity in human otitis media.
AB  - Chronic otitis media is a common problem associated with a nonintact tympanic
      membrane frequently involving Staphylococcus aureus and Pseudomonas aeruginosa.
      The virulence of Pseudomonas bacteria is related to the production of two matrix
      metalloproteinases, elastase and alkaline protease. Serine proteases, such as
      neutrophil elastase, are produced by the host inflammatory response. These
      proteases are thought to contribute to tissue destruction and assist bacterial
      invasion during infection. This preliminary study was done to identify protease
      activity in otorrhea samples from patients with otitis media and a nonintact
      tympanic membrane and to examine the ability of selective protease inhibitors to
      decrease protease activity. Ilomostat (galardin) is a synthetic, specific
      inhibitor of matrix metalloproteinases including P. aeruginosa elastase and
      alkaline protease, whereas alpha1-antitrypsin inhibits serine proteases including
      neutrophil elastase. Samples were collected and cultured from 20 patients with
      otorrhea resulting from tympanic membrane perforations or pressure-equalization
      tubes. A protease assay that used azocasein as the substrate was used to quantify
      protease activity, with and without addition of selective protease inhibitors.
      Cultures revealed P. aeruginosa alone in 7 samples, P. aeruginosa plus other
      organisms in 10, and S. aureus alone in 3. Protease activity was detected in 15
      (75%) of the samples. A statistically significant (p < 0.05) decrease in protease
      activity was seen with the addition of alpha1-antitrypsin or Ilomostat plus
      alpha1-antitrypsin, but not with Ilomostat alone. Analyzing the 10 samples with
      the highest protease activity, a statistically significant decrease in activity
      was seen with Ilomostat or alpha1-antitrypsin alone and with both Ilomostat and
      alpha1-antitrypsin together. Bacteriologic type, source of sample, age and gender
      of the subject, and duration of infection were not significantly related to
      protease activity. This is the first study to quantify protease activity and
      inhibition by selective protease inhibitors in human otorrhea. Protease
      inhibitors effectively decrease protease activity in most cases and in addition
      to standard antibiotic therapy might prove beneficial in the treatment of otitis
      media with a nonintact tympanic membrane. This study supports future clinical
      investigations into the role of proteases and inhibition of protease activity in
      the treatment of otitis media.

PMID- 9781989
TI  - Is postoperative intensive care monitoring necessary after
      uvulopalatopharyngoplasty?
AB  - We conducted a retrospective review of 347 consecutive patients who underwent
      surgical treatment for obstructive sleep apnea syndrome. We analyzed
      perioperative data to identify the nature and rate of complications in an attempt
      to determine whether intensive care unit monitoring is needed after
      uvulopalatopharyngoplasty (UPPP) and associated procedures including septoplasty,
      tonsillectomy, turbinate reduction, geniohyoid advancement, and tracheostomy. In
      the 347 cases, 14 complications occurred (4%), including 5 involving the airway,
      5 postoperative hemorrhages, and 4 complications classed as "other," including
      dehiscence of a tracheostomy flap, abdominal ileus, urine retention, and
      increased creatinine concentration. We found no difference between preoperative
      lowest oxygen saturation and oxygen-saturation readings in the postoperative
      period and no correlation between complication rate and apnea severity. An
      association was detected between multiple simultaneous procedures and the
      development of complications: 50% of the patients in whom complications developed
      had undergone nasal procedures along with UPPP, compared with only 15% of the
      patients without complications. Except for one patient, all complications that
      occurred on the surgical ward were treated without transfer to the intensive care
      unit. Although surgery on the upper airway must be performed with caution in
      patients with sleep apnea, our findings suggest that UPPP is a safe procedure and
      that postoperative monitoring in an intensive care setting is not necessary for
      most patients.

PMID- 9781990
TI  - Sinusitis in neurologically impaired children.
AB  - The microbiologic features of infected sinus aspirates in nine children with
      neurologic impairment were studied. Anaerobic bacteria, always mixed with aerobic
      and facultative bacteria, were isolated in 6 (67%) aspirates and aerobic bacteria
      only in 3 (33%). There were 24 bacterial isolates, 12 aerobic or facultative and
      12 anaerobic. The predominant aerobic isolates were Klebsiella pneumoniae,
      Escherichia coli, and Staphylococcus aureus (2 each) and Proteus mirabilis,
      Pseudomonas aeruginosa, Haemophilus influenzae, Moraxella catarrhalis, and
      Streptococcus pneumoniae (1 each). The predominant anaerobes were Prevotella sp.
      (5), Peptostreptococcus sp. (4), Fusobacterium nucleatum (2), and Bacteroides
      fragilis (1). Beta-lactamase-producing bacteria were isolated from 8 (89%)
      patients. Organisms similar to those recovered from the sinuses were also
      isolated from tracheostomy site and gastrostomy wound aspirates in five of seven
      instances. This study demonstrates the uniqueness of the microbiologic features
      of sinusitis in neurologically impaired children, in which, in addition to the
      organisms known to cause infection in children without neurologic impairment,
      facultative and anaerobic gram-negative organisms that can colonize other body
      sites are predominant.

PMID- 9781991
TI  - Microscopic examination of routine tonsillectomy specimens: is it necessary?
AB  - Controversy continues to exist regarding the routine histologic examining of
      tonsillectomy specimens. Proponents suggest that among other reasons, missing an
      important diagnosis such as occult malignancy or granulomatous disease and
      possible medicolegal consequences argue in favor of routine histologic
      examination. Others state that we should consider the very low yield of
      significant histologic findings in routine tonsillectomy specimens and its added
      cost. We performed a retrospective evaluation of all cases of patients who
      underwent tonsillectomy with or without adenoidectomy between January 1992 and
      July 1996. Two hundred eighty-eight charts were evaluable. Group 1 consisted of
      all tonsillectomy specimens that were subjected to gross examination only. Group
      2 consisted of all tonsillectomy specimens that were subjected to gross
      examination as well as microscopic examination. In group 1, no abnormal gross
      findings were noted. Group 2 consisted of specimens from an older population with
      a mean age of 21.6 years. There were 43 patients older than 20 years old in group
      2, and in all cases except four the preoperative clinical impression correlated
      with the microscopic findings. Occult malignancy was found in only one of these
      four patients. No cases of granulomatous disease were discovered. Overall, no
      patients except one had any change in postoperative treatment on the basis of the
      results of microscopic examination. We believe that routine microscopic
      examination of tonsillectomy specimens results in unnecessary cost and
      consumption of resources and time. Microscopic examination should be done in only
      selected cases such as in patients with grossly asymmetric tonsils or in patients
      with a history of malignancy.

PMID- 9781992
TI  - Ultra high resolution nonenhanced fast spin echo magnetic resonance imaging: cost
      effective screening for acoustic neuroma in patients with sudden sensorineural
      hearing loss.
AB  - The financial burden for the evaluation of patients for acoustic neuroma in an
      otolaryngology practice is substantial. Patients with sudden sensorineural
      hearing loss represent a portion of that population seen with unilateral,
      asymmetric auditory symptoms who require investigation for acoustic neuroma. For
      these patients, gadolinium-enhanced magnetic resonance imaging is the diagnostic
      gold standard. Auditory brain stem response testing has been used in the past as
      a screening test for acoustic neuroma, but its apparent sensitivity has fallen as
      the ability to image smaller acoustic neuromas has improved. Fast spin echo
      magnetic resonance imaging techniques without gadolinium have been shown to be as
      effective in the detection of acoustic neuroma as contrast-enhanced magnetic
      resonance imaging. Limited nonenhanced fast spin echo magnetic resonance imaging
      now provides an inexpensive alternative for high-resolution imaging of the
      internal auditory canal and cerebellopontine angle. Fast spin echo magnetic
      resonance imaging can now be done at a cost approximating auditory brain stem
      response testing while providing the anatomic information of contrast-enhanced
      magnetic resonance imaging. Cost analysis was done in the cases of 58 patients
      with sudden sensorineural hearing loss by comparing the costs for routine workup
      and screening of acoustic neuroma with the cost of fast spin echo magnetic
      resonance imaging with the use of screening protocols based on literature review.
      The potential cost savings of evaluating patients with sudden sensorineural
      hearing loss with fast spin echo magnetic resonance imaging for acoustic neuroma
      was substantial, with a 54% reduction in screening costs. In an era of medical
      economic scrutiny, fast spin echo magnetic resonance imaging has become the most
      cost-effective method to screen suspected cases of acoustic tumors at our
      institution by improving existing technology while reducing the cost of providing
      that technology and eliminating charges for impedance audiometry, auditory brain
      stem response testing, and contrast-enhanced magnetic resonance imaging.

PMID- 9781994
TI  - Endoscopic sinus surgery with magnetic resonance imaging guidance: initial
      patient experience.
AB  - We report the first endoscopic surgeries performed with patients under general
      anesthesia using intraoperative guidance with MRI. The procedures were
      experimental and intended to test (1) the unusual working environment of a unique
      new "open-configuration" MRI unit for head and neck surgery, and (2) real-time
      image guidance. Twelve patients underwent endoscopic sinus surgery while under
      general anesthesia in a new open MRI unit that provides the surgeon with access
      to the patient while imaging is performed. Eleven patients had chronic sinusitis
      (eight of them had bilateral disease), and one had a right nasoethmoid and antral
      tumor. All 12 surgeries were performed without complications. Both the endoscopic
      view and the MRI scans were available at the surgical field. The image plane was
      surgeon controlled, and the MRI updated images in as little as 14 seconds. MRI
      provided adequate visualization of both the disease and the related anatomy and
      allowed the surgeon to navigate during the procedure. The intraoperative data
      reflect the tissue changes during surgery and provide optimum feedback for
      surgical guidance. Although the operating environment poses some limitations, it
      has become apparent that intraoperative MRI has a role in the treatment of head
      and neck disorders and warrants further study.

PMID- 9781993
TI  - Revision stapedectomy for incus erosion: long-term hearing.
AB  - One of the most common ossicular problems in revision stapedectomy is the eroded
      incus. Revision surgery has been reported as successful in 70% to 80% of cases at
      1 year. Little is written about long-term results or the association of erosion
      with various prostheses. We evaluated 83 cases from 1 to 20 years, including
      multiple revisions. In 23 cases the erosion was seen at initial stapedectomy.
      Surgery was performed with the patient under local anesthesia, with the use of
      the Lippy modified prosthesis. Initial success was seen in 72% (41/57),
      satisfactory results in 90%, no change in 5%, and none worse. At 10 years,
      success had declined to 50% (7 of 14), with 80% satisfactory. The numbers for
      multiple revisions were lower. Success in nonrevision cases was 90% (21 of 23),
      dropping to 86% at 10 years, with satisfactory results in 100%. The type of
      prosthesis associated with erosion was a crimped wire in 34% (24 of 70), a
      plastic strut in 23%, and a Robinsion prosthesis in 17%. We conclude that the
      risk of incus erosion appears less with the Robinson prosthesis. The Lippy
      modified prosthesis yields good long-term results, particularly when erosion is
      seen at initial stapedectomy. Results worsen with subsequent revision.

PMID- 9781996
TI  - Overlay grafting for lateral nasal wall concavities.
AB  - One of the most difficult maneuvers in rhinoplasty is achieving a straight dorsum
      in the patient with a crooked nose. Often this deformity is a result of trauma
      involving the bony and cartilaginous vaults, resulting in nasal bone fractures
      and avulsion of the lateral cartilages into the nasal airway. Reduction of nasal
      bone fractures is fairly straightforward, but the repair of nasal cartilage
      trauma is more problematic. The cartilage of the nasal vault possesses fibrous
      attachments, which when disturbed, are difficult to reestablish. Overlay grafts
      are known to be effective in filling these defects and creating the illusion of a
      straight nose. In this series, during an 8-year period, 89 grafts were placed
      over lateral nasal wall concavities during rhinoplasty. Results after a minimum
      of 1 year follow-up are reviewed, as well as technique, materials, complications,
      revision rate, and patient satisfaction.

PMID- 9781995
TI  - Role of antral puncture in the treatment of sinusitis in the intensive care unit.
AB  - OBJECTIVE: The objective of this study was to determine whether maxillary sinus
      puncture caused an alteration in antibiotic treatment and thus affected the
      outcome of sinusitis in the intensive care unit. STUDY DESIGN: A retrospective
      review was done of cases of maxillary sinus puncture between 1991 and 1994.
      RESULTS: Forty-two patients were identified. All patients had findings suggestive
      of sinusitis on plain sinus films or CT scans of the sinuses. Twenty-five
      punctures (60%) recovered pus, of which 80% grew organisms. Fourteen patients
      (33%) had a negative lavage, and 12% of these samples grew organisms (p = 0.001).
      Sixty-eight percent of the cultures identified a single organism compared with
      32% with multiple organisms. Gram-negative organisms were found most commonly,
      followed by anaerobes. In 57% of the cases antibiotic therapy was changed. In 77%
      of the cases the change was directed by the culture result and in 35% the therapy
      was changed despite a negative culture result (p = 0.002). Resolution of symptoms
      occurred in 83% of patients who had antibiotics changed whereas with no change in
      antibiotics only 42% had resolution (p = 0.001). CONCLUSION: A sinus puncture
      seems to be helpful in patients with fever and positive findings on sinus films.
      If pus is obtained by maxillary puncture, a positive culture may be found in 80%
      of the cases. Changes in antibiotic regimen on the basis of culture findings seem
      to give a better outcome.

PMID- 9781997
TI  - Normative standards for nasal cross-sectional areas by race as measured by
      acoustic rhinometry.
AB  - Acoustic rhinometry evaluates the geometry of the nasal cavity with acoustic
      reflections and provides information about nasal cross-sectional area and nasal
      volume within a given distance. Variations in internal nasal diameters have
      attracted increased interest since the advent of endoscopic surgical techniques.
      Race is known to be one of the most important factors affecting the nasal
      structure. In this study, we evaluated 106 healthy adult volunteers with acoustic
      rhinometry to determine internal nasal diameters and volumes and obtained
      normative data for four racial/ethnic groups. The data were analyzed with regard
      to race, sex, height, and weight. All measurements were made before and after the
      application of a topical nasal decongestant so that the effects of the nasal
      cycle were eliminated by decongestion.

PMID- 9781998
TI  - Model for optimal space and staff efficiency in an otolaryngology clinic.
AB  - Maximizing efficiency of staff and resources is one method of reducing costs
      without affecting quality. Using a methodology similar to that used to maximize
      efficiency of airline-gate use, we developed a model with which to evaluate
      nursing support staff and clinical examining-room resources in a general
      otolaryngology clinic. For 144 patients over 7 consecutive clinic days, with four
      otolaryngologists and various combinations of support staff and examining rooms,
      we measured space and staff resource use, including total clinic time, number of
      patients seen, patient waiting time, physician and nurse productivity, and
      examining-room use. A simulation model was used as the medium of analysis to
      define parameters of the patient encounter. We identified optimal efficiency when
      there were three examining rooms and one and one-half nursing staff per physician
      or five examining rooms and three nursing staff for two simultaneously practicing
      physicians. Compared with a model of two rooms and one nursing staff member, our
      ideal model increased the percentage of the physicians' time spent in direct
      contact with patients from 84% to 92%. Visit length decreased from 81 minutes to
      57 minutes, the average time from check-in to examination decreased from 47 to 16
      minutes, and it became possible for three additional patients to be seen each
      day. Additional rooms and support staff, in comparison with the optimally
      efficient distribution, did not significantly affect these parameters. Maximizing
      efficiency with the use of this methodology can decrease waiting times for
      patients, resulting in greater patient satisfaction, improved physician
      productivity, total number of patients seen, and increased total contact time
      between physicians and patients.

PMID- 9781999
TI  - Isolated mucoepidermoid carcinoma in the neck.

PMID- 9782000
TI  - Otolaryngologic manifestations of acquired syphilis.

PMID- 9782001
TI  - Thyroiditis and thyroid cancer.

PMID- 9782002
TI  - Impression-material foreign bodies of the middle ear and external auditory canal.

PMID- 9782003
TI  - Differential expression of the murine Ly-6A/E antigen homolog of human squamous
      cell carcinoma antigen E48 during malignant transformation and tumor progression
      of squamous cell carcinoma line Pam 212.
AB  - The mRNA differential display method detected increased expression of the mRNA of
      an immune recognition antigen known as Ly-6A/E after malignant transformation of
      the murine squamous cell carcinoma line Pam 212. Subsequent loss of expression of
      Ly-6A/E occurred with metastatic tumor progression of Pam in vivo. Ly-6 molecules
      have been implicated in immune cell recognition and signal transduction and are
      homologous to the human E48 SCC antigen that has been shown to be involved in
      cell-cell recognition. These observations suggest that loss of Ly-6A/E antigen
      may contribute to tumor progression and metastasis of squamous cell carcinoma
      through decreased tumor-lymphocyte or tumor-tumor recognition.

PMID- 9782004
TI  - Cellular immune defect caused by postsurgical radiation therapy in patients with
      head and neck cancer.
AB  - The effects of locoregional postoperative radiation therapy (60 Gy on average) on
      cellular immunity were investigated in 11 patients with squamocellular carcinomas
      of the oral cavity, pharynx, or larynx. During radiation treatment, the total
      lymphocyte counts, CD8+ T-lymphocyte count, and especially CD4+ T-lymphocyte
      count decreased significantly. The mean CD4+ T-lymphocyte counts dropped from an
      average of 739/microl to 183/microl (p <0.001), and the CD4+/CD8+ quotient also
      decreased significantly. Not only the lymphocyte counts but also the in vitro
      lymphocyte stimulation responses to several mitogens decreased, with reductions
      averaging 10% to 50% of normal responses by the end of radiation therapy. Within
      3 to 4 weeks after radiation therapy, the CD4+ T-lymphocyte counts and the in
      vitro lymphocyte stimulation responses showed a tendency toward normalization.
      This study shows that postoperative locoregional radiation therapy in patients
      with head and neck cancer induces a severe generalized impairment of cellular
      immunity.

PMID- 9782005
TI  - Phonatory results after laser surgery for glottic carcinoma.
AB  - OBJECTIVE: To identify the influence of type and extent of surgery on
      postoperative voice parameters after endoscopic laser resection for glottic
      carcinoma. SETTING AND DESIGN: A multidisciplinary university-based head and neck
      cancer center. Objective and subjective measures of voice were correlated with
      type and extent of surgery following a standardized classification in a
      prospective study including 80 patients. SUBJECTS AND METHOD: The postoperative
      mechanism of phonation was assessed by videostroboscopy 6 months after surgery at
      the earliest. A phonetogram was produced, and its area was calculated (relative
      phonetogram (RP)) in relation to a gender-different normal phonetogram. Two
      speech therapists (ST) and a trained otolaryngologist (TO) rated each voice
      independently for communication ability in a grade from 1 (poor) to 5 (near
      normal). RESULTS: After simple cordectomy the means were as follows: RP = 24.8%,
      TO = 3.26, and ST = 3.33. When the anterior commissure was completely preserved,
      mean results were better (RP = 34%, TO = 3.92, ST = 3.83). Results were worse
      after extended cordectomy (RP = 14.7%, TO = 2.82, ST = 3.00) and transglottic
      resection (RP = 13.7%, TO = 2.30, ST = 2.86) but were similar within these two
      groups. The parameters RP TO, and ST do not differ significantly between the
      group who had speech therapy after surgery (n = 33) and the group who did not (n
      = 47). Voice production at glottic level yields better results for every
      parameter than supraglottic substitute phonation. The amount of tissue removed
      was less significant. CONCLUSION: Postoperative phonatory results correlate with
      the postoperative mechanism of phonation. There is no linear correlation with the
      amount of tissue removed. Comparison of similar types of resection preservation
      of the anterior commissure plays a key role. From the data in this study, there
      is no evidence for a significant benefit from speech therapy. The parameter RP is
      an effective and relatively simple parameter to complete auditory voice
      assessment.

PMID- 9782006
TI  - Caustic injury of the larynx.

PMID- 9782007
TI  - Pancreas and islet transplantation.

PMID- 9782008
TI  - Registers for patients with familial tumours: from controversial areas to common
      guidelines.

PMID- 9782009
TI  - Hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma is one of the world's most common
      malignancies. The aims of the present paper are to review data on (1)
      epidemiology and screening programmes for the early detection of the tumour and
      (2) advances in the diagnostic imaging and management. METHODS: Relevant English
      language articles, published between January 1985 and December 1997, were
      reviewed. Articles were identified through Medline search, using the key words
      'hepatocellular carcinoma'. Articles cited in the bibliographies of these
      articles were searched manually. RESULTS: Hepatocellular carcinoma has a
      heterogeneous geographical distribution. Although its risk factors have been
      identified, the efficacy of screening programmes remains uncertain. Imaging has
      improved substantially with the recent application of dual-phase helical computed
      tomography and magnetic resonance imaging employing specific contrast agents. The
      comparative efficacy of conservative therapy and surgical resection is uncertain,
      since well controlled trials are lacking. CONCLUSION: Hepatocellular carcinoma is
      commonly a problem of two diseases, the malignancy itself and cirrhosis. This
      renders treatment rarely curative, even when surgical resection can be applied in
      a technically successful sense. Liver transplantation could be a definitive
      treatment but this is plagued by limited donor resources.

PMID- 9782010
TI  - Pseudomyxoma peritonei.
AB  - BACKGROUND: Pseudomyxoma peritonei is an unusual condition in which gelatinous
      fluid collections are associated with mucinous implants on the peritoneal
      surfaces and omentum. The pathological origin and ideal treatment of the
      condition are subjects of debate. METHODS: An unrestricted Medline search over
      1986-1997 was performed for pseudomyxoma peritonei. RESULTS AND CONCLUSIONS:
      There is increasing evidence that pseudomyxoma peritonei is a neoplastic
      condition which usually arises from a primary adenoma or adenocarcinoma of the
      appendix. Reported series include a spectrum of pathological lesions, from
      entirely benign ruptured mucocele to advanced carcinoma. This, and the rarity of
      the condition, limit the conclusions that can be drawn regarding its treatment
      and prognosis. Most authorities agree that a thorough surgical debulking should
      be made. In most cases this will be a difficult and time-consuming undertaking,
      possibly requiring cooperation between two or more specialists and consideration
      of delivering intraperitoneal adjuvant therapy during or immediately after
      surgery. Treatment therefore requires a planned approach with accurate
      preoperative assessment of the diagnosis and the extent of the condition. There
      is some largely anecdotal evidence in favour of intraperitoneal chemotherapy and
      radioisotope treatment. Ultraradical surgery, with heated intraoperative and
      further postoperative chemotherapy, is strongly advocated by one group but
      remains contentious. The majority of patients will eventually suffer recurrence.
      The 5-year survival rate ranges from 53 to 75 per cent, but outcomes vary widely
      between relatively benign and malignant subgroups.

PMID- 9782011
TI  - Acute non-traumatic arm ischaemia.
AB  - BACKGROUND: Much attention has been paid to the management of acute leg
      ischaemia. Acute arm ischaemia is perceived as less of a problem because the risk
      of limb loss is lower. After conservative treatment up to half the patients have
      late symptoms, such as forearm claudication. METHODS: This study was a review of
      all published English language data on acute arm ischaemia. The entire Medline
      database was searched and other references were derived from the material
      perused. There were no randomized or controlled studies. RESULTS: The incidence
      of acute arm ischaemia is one-fifth that of acute leg ischaemia. Patients with
      arm ischaemia tended to be older with a mean age of 74 years compared with 70
      years for acute leg ischaemia. Since the development of the embolectomy catheter,
      embolectomy can be performed in most patients under local anaesthetic. Collected
      outcome included successful restoration of the circulation in 65-94 per cent of
      patients and amputation in 0-18 per cent. The mortality rate ranged from 0 to 19
      per cent, despite the use of local anaesthesia, mostly from associated cardiac
      disease. Management by a vascular specialist may be beneficial, particularly in
      complex cases. CONCLUSION: An active approach to the management of acute arm
      ischaemia is safe and effective and reduces the risk of late disabling symptoms.

PMID- 9782012
TI  - Lymphatic mapping and sentinel node biopsy in breast cancer.
AB  - BACKGROUND: Sentinel lymph node biopsy is a recently developed, minimally
      invasive technique for staging the axilla in patients with breast cancer. It has
      been suggested that this technique will avoid the morbidity associated with more
      extensive axillary dissection. A wide range of different methods and materials
      has been employed for lymphatic mapping, but there has been little consensus on
      the most reliable and reproducible technique. METHODS: This is a comprehensive
      review of all published literature on sentinel node biopsy in breast cancer,
      using the Medline and Embase databases and cross-referencing of major articles on
      the subject. RESULTS AND CONCLUSION: Sentinel node biopsy is a valid technique in
      breast cancer management, providing valuable axillary staging information. The
      optimal technique of lymphatic mapping utilizes a combination of vital blue dye
      and radiolabelled colloid. However, there remain controversial issues which
      require to be resolved before sentinel node biopsy becomes a widely accepted part
      of breast cancer care.

PMID- 9782014
TI  - Prospective evaluation of magnetic resonance cholangiography to detect common
      bile duct stones before laparoscopic cholecystectomy.
AB  - BACKGROUND: With the advent of laparoscopic cholecystectomy, endoscopic
      retrograde cholangiography (ERC) is frequently employed before operation to
      detect common bile duct stones. However, this is an invasive technique with
      recognized complications. This study evaluated the accuracy of magnetic resonance
      cholangiography (MRC) to detect choledocholithiasis in selected patients before
      laparoscopic cholecystectomy. METHODS: Patients scheduled for elective
      laparoscopic cholecystectomy, with risk factors for common bile duct stones,
      underwent MRC followed by ERC or peroperative cholangiography. RESULTS: Over a 2
      year period 40 patients were studied. MRC had a sensitivity of 88 per cent,
      specificity of 93 per cent, positive predictive value of 78 per cent and negative
      predictive value of 97 per cent for the detection of common bile duct stones.
      CONCLUSION: MRC is a simple non-invasive method for preoperative screening for
      common bile duct stones in at-risk patients. In this study it would have reduced
      the need for ERC by three-quarters.

PMID- 9782013
TI  - Subparietal hepaticojejunal access loop for the long-term management of
      intrahepatic stones.
AB  - BACKGROUND: The subparietal hepaticojejunal biliary access loop is a recognized
      technique for the long-term management of primary intrahepatic stone disease.
      This paper assesses the results of this approach in a series of South African
      patients. METHODS: Between 1985 and 1997, 21 patients, of mean age 34 (range 24
      66) years, underwent surgical extraction of intrahepatic stones and formation of
      an hepaticojejunal access loop. The access loop was subsequently used for further
      stone removal and stricture dilatation. Patients were followed prospectively
      (median 47 months) and details of the number and type of procedures performed,
      stone clearance rates, morbidity and subsequent outcome were recorded. RESULTS:
      The distribution of intrahepatic stones was left lobe in 13 of 21 patients, right
      lobe in one and bilateral in seven. Six patients underwent additional left
      lobectomy at the initial operation because of associated atrophy of the left
      lobe. Following operation, stone removal and/or stricture dilatation was
      performed on 97 occasions (median 4 (range 0-24) procedures per patient).
      Complete stone clearance was achieved in 17 of 21 patients with partial clearance
      in the remaining four. There were no major complications and no deaths associated
      with the procedures. CONCLUSION: The subparietal access loop permits long-term
      access to the intrahepatic ducts allowing removal of stones and dilatation of
      strictures with minimal patient discomfort and low morbidity.

PMID- 9782015
TI  - Popliteal artery entrapment syndrome: collaborative experience of the Joint
      Vascular Research Group.
AB  - BACKGROUND: Popliteal artery entrapment syndrome (PAES) is rare and probably
      underdiagnosed. This study reviewed a collected experience. METHODS: Patients
      were identified by the Joint Vascular Research Group (vascular surgeons from ten
      hospitals serving a population of approximately four million) during 1984-1995.
      Case notes were reviewed. RESULTS: Twenty-one legs in 17 patients were identified
      with PAES. There were 15 men and two women. The median age at presentation was 29
      (range 14-45) years. One patient was excluded because no further information was
      available. PAES was bilateral in four patients in whom three legs were
      asymptomatic. At presentation, the duration of symptoms ranged from a few hours
      (acute leg ischaemia) to intermittent claudication of 6 years' duration. Primary
      investigation included angiography (20 patients), duplex imaging (four), plain
      radiography (one) and magnetic resonance imaging (one). In two cases, attempted
      thrombolysis failed. Surgery was carried out on 17 legs but failed in two. No
      amputations were required. Following surgery, 12 legs were asymptomatic and five
      had residual symptoms. CONCLUSION: PAES should be excluded in young patients with
      intermittent claudication or acute ischaemia.

PMID- 9782016
TI  - Lower limb surveillance following autologous vein bypass should be life long.
AB  - BACKGROUND: The aim of the study was to investigate whether infrainguinal vein
      graft surveillance can be stopped at 1 year without prejudicing graft or leg
      survival. METHODS: Data were collected prospectively on 351 infrainguinal vein
      bypass grafts (326 patients) that had been entered into a vein graft surveillance
      programme between 1988 and 1997. RESULTS: Some 104 grafts (30 per cent) developed
      significant new vein graft stenoses, 95 (91 per cent) of which occurred within 12
      months. After 1 year, the risk of developing a significant graft stenosis was 3
      per cent per year. Sixty-nine grafted limbs (20 per cent) developed new arterial
      inflow or run-off stenoses that required intervention, but only 37 (54 per cent)
      occurred within the first year, after which the risk was 9 per cent per year. The
      overall risk of developing a new vein graft or arterial stenosis after 1 year was
      10 per cent per year. CONCLUSION: The incidence of vein graft stenosis decreases
      significantly 1 year after operation but there is still at risk of developing
      potentially graft-threatening arterial stenoses. Legs that have undergone
      infrainguinal vein bypass grafting should continue to be monitored in a
      surveillance programme for life.

PMID- 9782017
TI  - Marimastat inhibits neointimal thickening in a model of human vein graft
      stenosis.
AB  - BACKGROUND: There is now accumulating evidence that matrix metalloproteinases
      (MMPs), the physiological mediators of matrix deposition and degradation, play an
      important role in the development of intimal hyperplasia following arterial
      bypass. This study investigated the effect of marimastat, an orally active
      specific MMP inhibitor, on neointima formation in cultured human saphenous vein.
      METHODS: Segments of human saphenous vein obtained from ten patients undergoing
      arterial bypass surgery were cultured for 14 days in serum-supplemented RPMI
      medium (controls) or in control medium supplemented with marimastat at three
      different concentrations (treatment groups). Following culture, half of each
      segment was prepared for histological examination and MMPs were extracted from
      the other half for gelatin zymography. RESULTS: Marimastat inhibited neointimal
      thickening in a concentration-dependent manner; inhibition was significant at 10(
      5) and 10(-6) mol/l (P=0.006). This observation was paralleled by a significant
      reduction in the levels of MMP-2 and MMP-9 in the tissues. CONCLUSION: Marimastat
      significantly reduced neointimal thickening in this laboratory model. MMP
      inhibitors may offer a potential therapeutic strategy in the prevention of
      intimal hyperplasia.

PMID- 9782018
TI  - Early results of a randomized trial of rifampicin-bonded Dacron grafts for extra
      anatomic vascular reconstruction. Joint Vascular Research Group.
AB  - BACKGROUND: The aim of this study was to determine whether the routine use of an
      antibiotic-bonded gelatin-coated Dacron graft could reduce the incidence of
      prosthetic graft infection. Extra-anatomic grafts were chosen for study as they
      have the highest risk of graft infection. This paper reports early results up to
      1 month after surgery. METHODS: This multicentre study involved 14 vascular units
      in the UK. A total of 257 patients underwent extra-anatomic bypass. Patients were
      randomized to rifampicin bonding (1 mg/ml rifampicin soak for 15 min before graft
      insertion) or a control group. Routine three-dose antibiotic prophylaxis was
      administered to patients in both groups. RESULTS: There were 178 men and 79 women
      of median age 69 (range 43-92) years. Rifampicin-bonded (n=123) and control
      (n=134) groups were well matched for clinical details, risk factors and operative
      techniques. No side-effects were noted from rifampicin bonding. Only one patient
      (in the control group) developed a graft infection and this proved fatal. There
      were no significant differences between bonded and unbonded grafts in terms of
      perioperative mortality rate (9 and 5 per cent respectively), median hospital
      stay (10 days for both groups), total infective complications (15 and 21 per cent
      respectively) or need for postoperative antibiotics (13 and 18 per cent
      respectively). CONCLUSION: Early results from this study have not identified any
      significant advantage in the routine use of rifampicin bonding, but the rate of
      graft infection was very low (0.4 per cent). Gelatin coating alone may provide
      protection against infection. Definitive recommendations about the role of
      antibiotic bonding cannot be made until longer follow-up becomes available.

PMID- 9782019
TI  - Outcome in patients with a large abdominal aortic aneurysm considered unfit for
      surgery.
AB  - BACKGROUND: The risk of rupture of large abdominal aortic aneurysms (AAAs)
      remains uncertain. This study aimed to provide data to help decide whether or not
      to operate on high-risk patients. METHODS: Clinicians were asked to refer all
      patients with an AAA, even if unfit or elderly. One hundred and ninety-two
      patients with an intact AAA of 5 cm or greater in diameter were seen in 9 years;
      59 had no elective operation and follow-up data were available for 57 at a
      minimum of 2 years. Initial AAA diameters were 5.0-5-9 cm (n=25) and 6.0 cm or
      more (n=32). Survival curves were constructed for both groups. RESULTS: At the
      end of the study 50 of 57 patients had died. Median survival was 18 (range 1-90)
      months. Twenty (35 per cent) suffered rupture at a median interval of 18 (range 1
      38) months. The risk of rupture within 3 years was 28 (95 per cent confidence
      interval 12-49) per cent for 5.0-5.9-cm AAAs and 41 (24-59) per cent for AAAs of
      6 cm or greater. In 133 elective AAA operations in fit patients the 30-day
      mortality rate was 3 per cent. CONCLUSION: The risk of rupture within 3 years of
      diagnosis of an AAA of 5 cm or greater exceeds the expected operative mortality
      rate for fit patients. However, the majority of patients unfit for surgery died
      from other causes, and only a few would have benefited from aneurysm repair.

PMID- 9782020
TI  - Glutaraldehyde as a possible cause of diarrhoea after sigmoidoscopy.
AB  - BACKGROUND: An outbreak of proctitis at the start of a colorectal cancer
      screening programme utilizing flexible sigmoidoscopy prompted scrutiny of the
      incidence of this complication and the role of glutaraldehyde in its aetiology.
      METHODS: Questionnaires completed 1 day and 3 months after sigmoidoscopy were
      reviewed for 388 patients, and glutaraldehyde levels in the recycled rinse water
      of the endoscope washing machine were measured. The incidence of symptoms in the
      subsequent 612 patients after installation of a washer that does not recycle
      rinse water was examined. RESULTS: Five patients (1.3 per cent) presented to
      hospital with bloody diarrhoea occurring immediately after a normal flexible
      sigmoidoscopy. Repeat examination confirmed the presence of proctitis. Symptoms
      subsided rapidly with either no treatment or steroid enemas. Eight additional
      patients (2.1 per cent) recorded similar problems but received no treatment and
      the symptoms settled spontaneously. Glutaraldehyde levels rose progressively in
      the rinse water after each wash cycle with 2 per cent glutaraldehyde solution.
      Only one possible case of proctitis (0.2 per cent) was identified from the
      questionnaires completed by 612 patients after changing to a washer that did not
      recycle the rinse water. CONCLUSION: These observations should prompt the careful
      assessment of cleaning techniques. The use of washing machines that do not
      recycle rinse water may avoid this complication.

PMID- 9782021
TI  - What patients think of day-surgery proctology.

PMID- 9782022
TI  - Combining the strength-duration curve of the external anal sphincter with
      manometry for the assessment of faecal incontinence.
AB  - BACKGROUND: The strength-duration curve of a muscle is thought to be a measure of
      its innervation. This study was designed to evaluate the ability of the strength
      duration curve of the external anal sphincter to discriminate between controls
      and patients with faecal incontinence. METHODS: Forty-three women with faecal
      incontinence due to sphincter weakness were studied together with 45 age-matched
      women with no disorders of defaecation. Strength-duration curves of the external
      anal sphincter and anorectal manometry were recorded for all subjects with the
      additional measurement of pudendal nerve terminal motor latency in the
      incontinent group. RESULTS: Logistic regression was performed using resting and
      voluntary squeeze pressures and current strengths at 28 different pulse durations
      to develop a predictive equation for incontinence. Only currents at 1 and 6 ms
      were significant predictors. When anorectal manometry data were included, only
      the current required to elicit contraction at 1 ms was necessary. The following
      regression equation can be applied to predict continence in this population with
      a sensitivity of 95 per cent and a specificity of 100 per cent: logit(P)=4.1605
      (0.0559 x squeeze pressure)-(0.1755 x resting pressure)+0.8622I(1 ms). A negative
      value indicates continence. CONCLUSION: The strength-duration curve, when used in
      conjunction with anorectal manometry, may have a role in the investigation of
      faecal incontinence.

PMID- 9782023
TI  - Cost-effectiveness in the management of patients with oesophageal cancer.
AB  - BACKGROUND: The aim of this study was to assess the relationship between clinical
      outcome, quality of life and cost for treatment modalities commonly employed in
      the management of oesophageal carcinoma. METHODS: A series of 51 patients
      diagnosed with oesophageal carcinoma in a 6-month period was used to derive a
      cost analysis profile for their treatment. All patients underwent quality of life
      assessment. Patients diagnosed in 1993 and managed in Newcastle upon Tyne were
      identified from the Northern Cancer Registry and Hospital Episode Statistics.
      Intervention profiles were documented for a 3-year follow-up period and cost
      analysis was conducted. A further 51 patients were recruited prospectively for
      quality-of-life studies. RESULTS: Some 139 individuals were identified
      retrospectively. Median survival was significantly better in patients treated by
      resection (n=31; median 20 months) than in those receiving palliative treatments
      (n=108; median 6 months) (P < 00001). Median cost was significantly greater in
      individuals who underwent resection (8070 pound sterling) than for patients
      subjected to a palliative strategy (radiotherapy 4720 pound sterling,
      brachytherapy 1790 pound sterling, laser 3540 pound sterling, intubation 2450
      pound sterling, no treatment 1390 pound sterling) (P < 0.01). When considering
      the median cost per month of life (after treatment) resection (457 pound
      sterling) compared favourably with the palliative options (range 342-1125 pound
      sterling). CONCLUSION: Surgical resection for oesophageal carcinoma confers
      greatest benefit in terms of survival. Costs are inherently greater in
      individuals undergoing resection but, allowing for time, resection is at least as
      cost-effective as other treatment modalities.

PMID- 9782024
TI  - Learning curve for oesophageal cancer surgery.
AB  - BACKGROUND: Surgical training and experience are frequently claimed to influence
      early and late outcome measures. The aim of this study was to examine any
      improvement in an individual surgeon's performance in one operation over a period
      of 7 years from initial appointment to date. METHODS: Patients undergoing Ivor
      Lewis subtotal oesophagectomy performed by a single surgeon between April 1990
      and December 1996 were identified from a prospectively compiled oesophageal
      cancer database. Operating time (abdominal, thoracic and 'one-lung time'), blood
      loss, transfusion requirements (intraoperative and total), extent of
      lymphadenectomy (number of lymph nodes sampled), intensive treatment unit (ITU)
      stay, hospital stay, postoperative morbidity and mortality, pathological stage,
      grade and survival were recorded. RESULTS: The records of 150 patients were
      identified for analysis. The cohort was split into five groups, each of 30
      patients operated on consecutively. Each of the groups was comparable for age,
      sex, smoking history, preoperative haemoglobin and creatinine levels, weight
      loss, American Society of Anesthesiologists' grade, and histological stage and
      grade of disease. Analysis of the variables pertaining to operation revealed a
      significant improvement with time including reduced single-lung operating time
      (P=0.01), reduced blood loss (P=0.03), reduced transfusion requirement (P <
      0.0001), reduced ITU stay (P< 0.0001), reduced inpatient stay (P< 0.0001) and an
      increased yield of lymph nodes (P < 0.0001). CONCLUSION: This study showed a
      continuing improvement in a surgeon's performance over a 7-year period. With the
      current trend to shorter training periods there is a case for continuing
      supervision of the 'fully trained' surgeon within highly specialist units.

PMID- 9782025
TI  - Detection of response to chemotherapy using positron emission tomography in
      patients with oesophageal and gastric cancer.
AB  - BACKGROUND: The aim of the study was to determine whether 2-[18F]-fluoro-2-deoxy
      D-glucose (FDG)-positron emission tomography (PET) could detect response to
      chemotherapy in patients with oesophageal and gastric cancer. METHODS: Fourteen
      patients underwent imaging before and after chemotherapy using FDG-PET. Computed
      tomography (CT), dysphagia scores and weight changes were used for comparison of
      evidence of response. Tumour to liver ratios (TLRs) and influx constants for FDG
      (K) were used for quantification purposes. RESULTS: Thirteen of 14 lesions were
      successfully imaged before therapy. Changes were seen in all follow-up scans,
      ranging from a complete response to a 15 per cent increase in tumour FDG uptake.
      Response was demonstrated by CT in four patients; all four had large reductions
      in FDG uptake after chemotherapy. Two patients with an increase in FDG uptake
      reported no improvement in dysphagia and continued to lose weight during therapy.
      CONCLUSION: Changes in tumour FDG uptake were seen in all tumours after
      chemotherapy. FDG-PET may have a role to play in the assessment of patients with
      upper gastrointestinal malignancy receiving chemotherapy.

PMID- 9782026
TI  - Scanning laser Doppler flowmetry and intraluminal recirculating gas tonometry in
      the assessment of gastric and jejunal perfusion during oesophageal resection.
AB  - BACKGROUND: The ability of the new techniques of scanning laser Doppler flowmetry
      and recirculating gas tonometry to measure changes in gastric serosal and mucosal
      blood flow respectively during oesophageal resection was assessed. METHODS:
      Changes in regional and total gastric blood flow were assessed in 16 patients
      undergoing oesophagectomy at three stages of the procedure. Laser Doppler images
      were analysed and perfusion expressed as mean perfusion units. Tonometric
      measurements of gastric and jejunal intramucosal pH (pHi) were made
      synchronously. RESULTS: There were significant falls in gastric perfusion
      measured with scanning laser Doppler flowmetry in all subjects between each
      measurement. Mean perfusion of the stomach fell 41 per cent after mobilization.
      There was a gradient of reduced perfusion between the antrum (mean fall 25 per
      cent) and the area used for the anastomosis in the fundus (mean fall 55 per
      cent). Before mobilization mean gastric and jejunal pHi were 7.37 and 7.46
      respectively. These fell to 7.18 and 7.37 respectively after mobilization and to
      7.29 and 7.38 after anastomosis. CONCLUSION: These new techniques could be
      employed at operation, appear to overcome the limitations of single-point laser
      Doppler flowmetry and saline tonometry, and have measured significant changes in
      gastric perfusion. They may have widespread clinical application.

PMID- 9782027
TI  - Pain after groin hernia repair.
AB  - BACKGROUND: The purpose of the study was to provide a detailed description of
      postoperative pain after elective day-case open inguinal hernia repair under
      local anaesthesia. METHODS: This was a prospective consecutive case series study.
      After 500 hernia operations in 466 unselected patients aged 18-90 years, pain was
      scored (none, light, moderate or severe) at rest, while coughing and during
      mobilization, daily for the first postoperative week and after 4 weeks. Pain
      scores were added together over the first postoperative week. RESULTS: On days 1,
      6 and 28, 66, 33 and 11 per cent respectively had moderate or severe pain while
      coughing or mobilizing. Total pain scores were higher while coughing or
      mobilizing than at rest (P < 0.001). Younger patients had higher total pain
      scores than older patients while coughing or mobilizing (P0< 0.01), but not at
      rest. No significant differences were found between types of surgery or hernia.
      CONCLUSION: Pain remained a problem despite the pre-emptive use of opioids, non
      steroidal anti-inflammatory drugs and local anaesthesia, irrespective of surgical
      technique.

PMID- 9782028
TI  - Repair of ventral hernias with expanded polytetrafluoroethylene patch.
AB  - BACKGROUND: Operations for large and recurrent abdominal hernias have a high
      associated recurrence rate, although it is lower when prosthetic material is
      used. Expanded polytetrafluoroethylene (ePTFE) seems to be the best tolerated
      prosthetic material in surgery. METHODS: A series of 45 ventral hernias repaired
      using ePTFE for closure or reinforcement of the herniorrhaphy has been evaluated
      prospectively. Thirty-six were midline incisional hernias and nine were
      transverse or pararectal ventral hernias. There were 13 recurrent ventral hernias
      and three defects were operated as an emergency procedure. The patch was sutured
      to the anterior aponeurosis with a running non-absorbable suture. Some other kind
      of intra-abdominal procedure was undertaken in 12 cases. RESULTS: ePTFE was well
      tolerated. Complications occurred in five patients. Major complications were
      found in three patients: cutaneous necrosis requiring a myocutaneous flap; and
      infection of the prosthesis (primary, and secondary to enterocutaneous fistula
      due to diverticulitis, both requiring removal of the patch). Mean follow-up was
      39 months and hernia recurrence occurred in only one patient. CONCLUSION: This
      clinical experience shows that ePTFE is a very reliable prosthetic material for
      the repair of abdominal wall hernias.

PMID- 9782029
TI  - Experimental study of the effect of intra-abdominal pressure during laparoscopy
      on tumour growth and port site metastasis.
AB  - BACKGROUND: The influence of raised intraperitoneal pressure during laparoscopy
      on tumour growth and port site metastasis is still unknown. METHODS: Tumour
      growth of colonic adenocarcinoma DHD/K12/TRb was measured after laparoscopy with
      carbon dioxide at different pressures (0, 5, 10 and 15 mmHg) in a rat model. Cell
      kinetics were determined after incubation with carbon dioxide (0, 5, 10 and 15
      mmHg) in vitro (n=60). Additionally, tumour growth was measured subcutaneously
      and intraperitoneally 4 weeks after laparoscopy at different intraperitoneal
      pressures (5, 10 and 15 mmHg) (n=100). RESULTS: In vitro tumour growth decreased
      significantly after incubation with carbon dioxide at 10 and 15 mmHg compared
      with a pressure of 0 or 5 mmHg. In vivo, mean(s.d.) intraperitoneal tumour weight
      was significantly increased after laparoscopy at 5 mmHg (919(1085) mg) and at 10
      mmHg (1274(1523) mg) (P< 0.05), but decreased again after laparoscopy with an
      intraperitoneal pressure of 15 mmHg (731(929) mg) compared with the control group
      (365(353) mg) (P=0.3). Mean(s.d.) subcutaneous tumour growth was promoted after
      laparoscopy at 5 mmHg (172(234) mg), at 10 mmHg (190(253) mg) and at 15 mmHg
      (178(194) mg) compared with controls (48(33) mg) (P < 0.05). CONCLUSION: In
      vitro, raised intraperitoneal pressure leads to suppression of tumour growth. In
      vivo, intraperitoneal tumour growth is suppressed only by higher pressure (15
      mmHg). Subcutaneous tumour growth is stimulated by carbon dioxide independently
      of the intraperitoneal pressure.

PMID- 9782030
TI  - Results of surgical resection of liver metastases from non-colorectal primaries.
AB  - BACKGROUND: Advances in the field of liver surgery have lowered its associated
      mortality and morbidity rates, and hepatic resection for metastatic disease is
      increasingly performed. There are few well defined guidelines for the
      heterogeneous group of non-colorectal metastases. This study analysed the risks
      and benefits of surgical resection for liver metastases from non-colorectal
      primaries. METHODS: A retrospective study was performed of 34 patients who
      underwent 37 operations over a 10-year period. Compilation of data from 141
      patients from eight additional recent series was performed in order to analyse
      the effect of histological type on survival. RESULTS: There were no perioperative
      deaths. Complications occurred after seven of 37 procedures. Actuarial survival
      rates were 61, 43 and 27 per cent at 1, 2 and 5 years. Survival was significantly
      improved for curative versus palliative resection (P < 0.05), and for single
      versus multiple metastases (P < 0.05). A strong correlation was observed between
      time to presentation with metastasis and length of survival (P< 0.0001). Survival
      was significantly better for patients with secondaries from neuroendocrine
      tumours (P < 0.0001), worse for those with intestinal adenocarcinomas (P <
      0.0001) and similar for patients with breast carcinoma (P > 0.5) when compared
      with the whole group. CONCLUSION: The low mortality and morbidity rates and the
      satisfactory survival figures reported justify this type of surgery for selected
      patients, in the absence of therapeutic alternatives.

PMID- 9782031
TI  - Effects of loperamide on ileoanal pouch function.
AB  - BACKGROUND: Opioid analogues are used to manage increased bowel frequency in
      patients with an ileoanal reservoir. The aim of the study was to determine the
      clinical efficacy of loperamide in patients with an ileoanal reservoir and to
      assess its effect on pouch motility. METHODS: Fourteen patients with a pouch who
      had normal pouch emptying and anal function were studied. Ambulatory pouch and
      anal motility, and stool weights, were recorded for 24 h while taking no
      medication and for 24 h while receiving 8 mg loperamide. In a second analysis,
      patients were divided on the basis of bowel frequency into those with 4 or fewer
      motions (good function; n=6) and those with more than 6 per day (poor function;
      n=8), to determine any differential effects of loperamide. RESULTS: Loperamide
      decreased median bowel frequency (no loperamide 5.5 versus loperamide 4.0,
      P=0.03) and 24-h stool weight (610 g versus 413 g, P=0.03) but not individual
      stool weights. Patients with poor function had both higher bowel frequency (8.0
      versus 3.5 per 24 h, P=0.004) and higher stool weight (728 g versus 430 g,
      P=0.05) with no treatment than those with good function. High-amplitude pouch
      pressure waves were greater in number before defaecation in patients with poor
      function and did not decrease with loperamide, in contrast to patients with good
      function. Pouch baseline pressure decreased after defaecation to a similar extent
      in both groups and was not affected by loperamide. CONCLUSION: Loperamide 8 mg
      per day reduces bowel frequency by reducing total stool weight, not individual
      stool weights. In patients with good function it also affects pouch motility.
      High bowel frequency is associated with increased pouch high-pressure waves.

PMID- 9782032
TI  - Third-degree obstetric perineal tear: long-term clinical and functional results
      after primary repair.
AB  - BACKGROUND: This study was designed to investigate the long-term clinical and
      anorectal functional results after primary repair of a third-degree obstetrical
      perineal rupture. METHODS: One hundred and fifty-six consecutive women who had a
      primary repair of a third-degree perineal rupture were sent a questionnaire and
      asked to undergo anorectal function testing (anal manometry, anorectal
      sensitivity, anal endosonography and pudendal nerve terminal motor latency
      (PNTML)) RESULTS: Some 117 women (75 per cent) responded. Anal incontinence was
      present in 47 women (40 per cent); however, in most cases only mild symptoms were
      present. In 40 women additional anorectal function tests were performed and
      compared with findings in normal controls. Mean(s.d.) maximum squeeze pressure
      (31(15) versus 63(17) mmHg, P< 0.001) was decreased and first sensation to
      filling of the rectum (88(47) versus 66(33) ml, P=0.03) and anal mucosal
      electrosensitivity (4.7(1.7) versus 2.5(0.8) mA, P=0.003) were increased compared
      with values in normal controls. In 35 women (88 per cent) a sphincter defect was
      found with anal endosonography. Factors related to anal incontinence were the
      presence of a combined anal sphincter defect (relative risk (RR) 1.7 (95 per cent
      confidence interval (c.i.) 1.1-2.8)) or subsequent vaginal delivery (RR 1.6 (95
      per cent c.i. 1.1-2.5)). CONCLUSION: Anal incontinence prevails in 40 per cent of
      women 5 years after primary repair of a third-degree perineal rupture. The
      presence of a combined sphincter defect or subsequent vaginal delivery increase
      the risk of anal incontinence.

PMID- 9782033
TI  - Laparotomy and laparoscopy differentially accelerate experimental flank tumour
      growth.
AB  - BACKGROUND: Surgery depresses host tumoricidal activity and may increase tumour
      growth. This study compared the effects of laparoscopy with laparotomy on
      extraperitoneal tumour growth and immune function in a murine model. METHODS:
      C57BL/6 female mice aged 8-10 weeks had tumours induced in the right flank (n=45)
      and were randomized to undergo halothane anaesthesia only, laparoscopy or
      laparotomy. Flank tumour volume was assessed over 10 days. A second group of
      animals (n=540) were randomized to undergo the same procedures and killed at 24,
      48 and 96 h. Splenocytes were harvested for natural killer (NK) cell and
      lymphokine activated killer (LAK) cell cytotoxicity studies. RESULTS: There was a
      significant increase in flank tumour growth in the first 48 h after laparotomy
      and laparoscopy compared with controls (P < 0.01). By 96 h the difference was
      only significant in the laparotomy group (P< 0.01). Both NK and LAK cell
      cytotoxicities were suppressed significantly (P < or = 0.03) from 24 h up to 96 h
      following laparotomy compared with control and laparoscopy groups. There was also
      a significant suppression in the laparoscopy group compared with controls in the
      first 48 h after operation (P < or = 0.02). CONCLUSION: Extraperitoneal tumour
      growth was significantly accelerated after laparotomy and correlated with
      significantly suppressed NK and LAK cytotoxicity for at least 4 days after
      operation. Laparoscopy had a shorter, less profound effect on tumour growth and
      immune function.

PMID- 9782034
TI  - Prospective randomized controlled trial of preservation of the intercostobrachial
      nerve during axillary node clearance for breast cancer.
AB  - BACKGROUND: Complications of axillary surgery occur due to severance of the
      intercostobrachial nerve (ICBN). The feasibility and benefit of preserving the
      ICBN to prevent sensory loss was studied prospectively. METHODS: Sensory symptoms
      and deficits were documented, and shoulder movement and arm circumference were
      measured at discharge and 3 months later in 120 patients randomized to either
      preservation or division of the ICBN. RESULT: Preserving the ICBN was feasible in
      39 (65 per cent) of the 60 patients randomized to the preservation group.
      Preserving the nerve prolonged the procedure by a median of 5 min. No difference
      in sensory symptoms between the groups was seen at 3 months. At 3 months 53 per
      cent of patients randomized to ICBN preservation had a sensory deficit compared
      with 84 per cent of those randomized to ICBN sacrifice (P < or = 0.05).
      CONCLUSION: Preserving the ICBN reduces the incidence of sensory deficit (but not
      symptoms) in patients after axillary clearance.

PMID- 9782035
TI  - Diagnosis and conservative management of intrathoracic leakage after
      oesophagectomy.
AB  - BACKGROUND: Although intrathoracic leakage is a major complication of
      oesophagectomy, precise data concerning diagnostic features and results of
      conservative treatment are lacking. METHODS: From 1986 to 1994, 409
      oesophagectomies with stapled oesophagogastrostomy were performed, including 358
      Lewis-Tanner and 51 Sweet procedures. A water-soluble contrast swallow was
      routinely performed on day 7 or later, before oral intake was begun. All patients
      except one received conservative non-surgical treatment, including nutritional
      support and perianastomotic drainage. RESULTS: Leaks were diagnosed in 38
      patients (9.3 per cent). The leakage rate was 7.8 per cent after the Lewis-Tanner
      procedure and 20 per cent after the Sweet procedure (P < 0.01). Eleven patients
      had no symptoms. Seven of the 27 patients with symptoms had a contrast swallow
      that was normal, and subsequently developed a confirmed fistula after the onset
      of oral intake. Five patients had to undergo reoperation. All asymptomatic
      patients and 18 symptomatic patients recovered. Nine patients died, mainly from
      multiple organ failure, including three who had reoperation for resection of the
      gastroplasty. CONCLUSION: The potential presence of clinically silent fistula and
      the deleterious role of oral intake still justify routine detection of leakage
      after oesophageal resection. Conservative treatment results in survival with
      preservation of the gastroplasty in most patients, unless multiple organ failure
      occurs.

PMID- 9782036
TI  - Abdominal ultrasonography in the diagnosis of colonic cancer.

PMID- 9782037
TI  - Multidisciplinary approach to biliary complications of laparoscopic
      cholecystectomy.

PMID- 9782038
TI  - Prospective randomized controlled trial to compare skin staples and polypropylene
      for securing the mesh in inguinal hernia repair.

PMID- 9782039
TI  - Randomized placebo-controlled trial of local anaesthetic infusion in day-case
      inguinal hernia repair.

PMID- 9782040
TI  - Functional results following the antegrade continence enema procedure.

PMID- 9782041
TI  - Temporary decompression after colorectal surgery: randomized comparison of loop
      ileostomy and loop colostomy.

PMID- 9782042
TI  - Mainstreaming contraceptive services in managed care--five states' experiences.
AB  - CONTEXT: The ongoing, rapid national transition from a health care financing and
      delivery system dominated by traditional indemnity insurance to one dominated by
      managed care has enormous implications for the accessibility of contraceptive
      services. METHODS: In each of five areas with relatively mature managed care
      environments (all of Colorado, Massachusetts and Michigan, as well as selected
      counties in California and Florida), all managed care organizations serving
      commercial or Medicaid enrollees were asked about their coverage of contraceptive
      services and the procedures for obtaining that care. In addition, all publicly
      funded family planning agencies in these areas were queried about their
      involvement with managed care plans, and representative samples of reproductive
      age women at risk of unintended pregnancy and enrolled in managed care plans were
      asked about their plan's coverage and their experiences in obtaining
      contraceptive services. RESULTS: Fifteen percent of health maintenance
      organizations and point-of-service plans did not cover all five of the most
      commonly used medical contraceptive methods, and another 6% covered none of the
      methods. Only half the plans informed enrollees--and even fewer informed
      enrollees insured indirectly as dependents--of whether they covered contraceptive
      services. One in four women in commercial plans were unsure whether their plan
      covered oral contraceptives, and two in three did not know if their plan covered
      the other medical methods. Only one in four commercial plans have brought
      community-based family planning providers into their networks, and more than half
      of all publicly funded family planning agencies reported having no contracts with
      managed care organizations. Finally, nearly one in three women in managed care
      plans reported difficulties in obtaining contraceptive services, with 13% of
      enrollees in commercial plans waiting at least four weeks for an appointment for
      contraceptive care. CONCLUSIONS: To adequately address the contraceptive needs of
      their employees, employers must ensure that the health insurance plans they
      purchase provide adequate coverage of contraceptive methods. For their part,
      managed care organizations and state Medicaid programs should examine their
      policies and procedures to ensure that services are easily accessible to women
      needing contraceptive care.

PMID- 9782043
TI  - Dual-method use among an ethnically diverse group of women at risk of HIV
      infection.
AB  - CONTEXT: Few U.S. women protect themselves against both pregnancy and sexually
      transmitted diseases (STDs) by using an efficient contraceptive method and a
      condom. Understanding the factors that influence dual-method use could help
      improve interventions aimed at encouraging protective behaviors. METHODS:
      Interviews were conducted with 552 low-income women at risk of HIV who attended
      public health or economic assistance facilities in Miami in 1994 and 1995.
      Multinomial logit analyses were used to determine the influence of women's
      background characteristics, perceived vulnerability to pregnancy and AIDS, and
      relationship characteristics on the odds of dual-method use. RESULTS: Overall,
      20% of the women used dual methods. Women who were not married, who worried about
      both pregnancy and AIDS, who had ever had an STD, who were confident they could
      refuse a sexual encounter in the absence of a condom and who made family planning
      decisions jointly with their partner were the most likely to use dual methods
      rather than a single method (odds ratios, 2.0-3.5); those who considered the
      condom only somewhat effective in preventing AIDS or who shared economic decision
      making with their partner were the least likely to use dual methods rather than a
      single method (0.5-0.6). The results were generally similar in analyses examining
      the odds of dual-method use involving an efficient contraceptive, except that
      black and Hispanic women were significantly more likely than whites to use
      condoms in conjunction with efficient contraceptives (3.3-7.1). CONCLUSIONS: Both
      women's individual characteristics and the context of their sexual relationships
      influence whether they simultaneously protect themselves from pregnancy and HIV.
      The involvement of male partners in family planning decision-making and women's
      control over economic decision-making ensure greater protection against HIV
      infection.

PMID- 9782044
TI  - Family communication about sex: what are parents saying and are their adolescents
      listening?
AB  - CONTEXT: Communication between parents and adolescents about sex, particularly in
      minority families, has been understudied; more information is needed both on
      which sex-related topics are discussed and on how their content is transmitted.
      METHODS: Parent-adolescent communication about 10 sex-related topics was examined
      in a sample of 907 Hispanic and black 14-16-year-olds. Chi-square analyses were
      performed to test for significant differences across the 10 topics in discussions
      reported by the adolescents (with either parent) and by the mothers. The openness
      of communication, parent-adolescent agreement about communication of topics and
      differences by gender and ethnicity were also examined. RESULTS: Significantly
      higher proportions of mothers and adolescents reported discussions of HIV or AIDS
      (92% by mothers and 71% by adolescents, respectively) and STDs (85% and 70%,
      respectively) than of issues surrounding sexual behavior, contraceptive use and
      physical development (27-74% for these other eight topics as reported by mothers
      vs. 15-66% as reported by adolescents). The gender of the adolescent and of the
      parent holding the discussion, but not the family's ethnicity, significantly
      influenced findings, with adolescents of both sexes more likely to report
      discussions with mothers than with fathers, and with parents more likely to
      discuss any of the 10 topics with an adolescent of the same gender than of the
      opposite gender. The likelihood of a topic being discussed and of mother
      adolescent agreement that a topic was discussed both increased with an increasing
      degree of openness in the communication process. CONCLUSIONS: Consistent with
      research among white samples, mothers of black and Hispanic adolescents are the
      primary parental communicators about sexual topics. To facilitate communication,
      educational programs for parents should cover not only what is discussed, but how
      the information is conveyed.

PMID- 9782046
TI  - Economic and personal factors affecting women's use of nurse-midwives in
      Michigan.
AB  - CONTEXT: The proportion of American women who use a nurse-midwife rather than an
      obstetrician to deliver their baby is increasing. Relatively little is known,
      however, about the determinants of a midwife-assisted birth. METHODS: Logistic
      regression analyses using birth-certificate data on 149,437 Michigan births in
      1990 examined the characteristics associated with midwife-attended births.
      RESULTS: Women who paid for childbirth with Medicaid were 3.5 times more likely
      than those paying with private insurance to use a certified nurse-midwife, net of
      controls for maternal characteristics; this effect varied significantly by race,
      with Medicaid payment increasing the odds of midwife use threefold among whites
      and nearly fivefold among nonwhites. The effect of education on midwife use also
      varied by race: A college education significantly increased the likelihood of
      midwife use among white women (odds ratio of 2.1), but higher education decreased
      that probability among nonwhite women (odds ratio of 0.74). Father's education
      and age, were also significantly associated with the likelihood of a midwife
      attended birth; the babies of college-educated fathers had higher odds of being
      delivered by a nurse-midwife, as did the babies of men in their 30s. CONCLUSIONS:
      The relationship between socioeconomic status and the use of midwives may not be
      as straightforward as previously thought. The patients of nurse-midwives are a
      diverse group whose socioeconomic characteristics and probable reasons for
      choosing a midwife over a physician vary widely.

PMID- 9782045
TI  - The effects of pregnancy planning status on birth outcomes and infant care.
AB  - CONTEXT: The planning status of a pregnancy may affect a woman's prenatal
      behaviors and the health of her newborn. However, whether this effect is
      independent or is attributable to socioeconomic and demographic factors has not
      been explored using nationally representative data. METHODS: Data were obtained
      on 9,122 births reported in the 1988 National Maternal and Infant Health Survey
      and 2,548 births reported in the 1988 National Survey of Family Growth. Multiple
      logistic regression analyses were employed to examine the effects of planning
      status on the odds of a negative birth outcome (premature delivery, low-birth
      weight infant or infant who is small for gestational age), early well-baby care
      and breastfeeding. RESULTS: The proportion of infants born with a health
      disadvantage is significantly lower if the pregnancy was intended than if it was
      mistimed or not wanted; the proportions who receive well-baby care by age three
      months and who are ever breastfed are highest if the pregnancy was intended. In
      analyses controlling for the mother's background characteristics, however, a
      mistimed pregnancy has no significant effect on any of these outcomes. An
      unwanted pregnancy increases the likelihood that the infant's health will be
      compromised (odds ratio, 1.3), but the association is no longer significant when
      the mother's prenatal behaviors are also taken into account. Unwanted pregnancy
      has no independent effect on the likelihood of well-baby care, but it reduces the
      odds of breastfeeding (0.6). CONCLUSIONS: Knowing the planning status of a
      pregnancy can help identify women who may need support to engage in prenatal
      behaviors that are associated with healthy outcomes and appropriate infant care.

PMID- 9782047
TI  - Teenage childbearing is not so bad after all...or is it? A review of the new
      literature.

PMID- 9782049
TI  - Abortion reporting in the United States: an examination of the federal-state
      partnership.

PMID- 9782048
TI  - Condom use among women choosing long-term hormonal contraception.
AB  - CONTEXT: Women who rely on long-term hormonal contraception may neglect to use
      condoms, and thus increase their risk of contracting sexually transmitted
      diseases, including AIDS. METHODS: Data from a prospective, multisite study were
      collected to examine the probability of condom use among 1,073 new users of
      either the contraceptive implant or injectable; users were interviewed when they
      accepted their method and again six months to one year later. Multivariate
      logistic regression analyses identified factors that significantly predicted the
      likelihood of dual method use. RESULTS: Condom use dropped markedly among women
      who adopted long-term hormonal contraception. The proportion who always used
      condoms in the previous three months fell from 21% at the time of adoption to 11%
      at follow-up. Among women with one sexual partner, this decrease was from 20% to
      10%; however, among those with more than one partner, use increased from 25% to
      31%. The factors significantly predicting dual method use included previous
      condom use (odds ratio of 2.5), receipt of AIDS-specific counseling (odds ratio
      of 1.6), the perception of being at some risk of AIDS at baseline (odds ratio of
      1.4) and having had more than one sexual partner over the study period (odds
      ratio of 5.4). In addition, injectable users, teenagers and black women were more
      likely than other women to use condoms with their hormonal method. CONCLUSIONS:
      Although condom use among all women declined markedly once they initiated long
      term hormonal contraception, frequency of condom use varied by subgroup and was
      associated with several factors. Most importantly, women with more than one
      sexual partner and those who received a message during counseling on the need to
      continue using condoms were more likely than others to use condoms in conjunction
      with the implant or injectable.

PMID- 9782050
TI  - Function from structure? The crystal structure of human phosphatidylethanolamine
      binding protein suggests a role in membrane signal transduction.
AB  - BACKGROUND: Proteins belonging to the phosphatidylethanolamine-binding protein
      (PEBP) family are highly conserved throughout nature and have no significant
      sequence homology with other proteins of known structure or function. A variety
      of biological roles have previously been described for members of this family,
      including lipid binding, roles as odorant effector molecules or opioids,
      interaction with the cell-signalling machinery, regulation of flowering plant
      stem architecture, and a function as a precursor protein of a bioactive brain
      neuropeptide. To date, no experimentally derived structural information has been
      available for this protein family. In this study we have used X-ray
      crystallography to determine the three-dimensional structure of human PEBP
      (hPEBP), in an attempt to clarify the biological role of this unique protein
      family. RESULTS: The crystal structures of two forms of hPEBP have been
      determined: one in the native state (at 2.05 A resolution) and one in complex
      with cacodylate (at 1.75 A resolution). The crystal structures reveal that hPEBP
      adopts a novel protein topology, dominated by the presence of a large central
      beta sheet, and is expected to represent the archaetypal fold for this family of
      proteins. Two potential functional sites have been identified from the structure:
      a putative ligand-binding site and a coupled cleavage site. hPEBP forms a dimer
      in the crystal with a distinctive dipole moment that may orient the oligomer for
      membrane binding. CONCLUSIONS: The crystal structure of hPEBP suggests that the
      ligand-binding site could accommodate the phosphate head groups of membrane
      lipids, therefore allowing the protein to adhere to the inner leaf of bilipid
      membranes where it would be ideally positioned to relay signals from the membrane
      to the cytoplasm. The structure also suggests that ligand binding may lead to
      coordinated release of the N-terminal region of the protein to form the
      hippocampal neurostimulatory peptide, which is known to be active in the
      development of the hippocampus. These studies are consistent with a primary
      biological role for hPEBP as a transducer of signals from the interior membrane
      surface.

PMID- 9782051
TI  - Structural basis of spectral shifts in the yellow-emission variants of green
      fluorescent protein.
AB  - BACKGROUND: Because of its ability to spontaneously generate its own fluorophore,
      the green fluorescent protein (GFP) from the jellyfish Aequorea victoria is used
      extensively as a fluorescent marker in molecular and cell biology. The yellow
      fluorescent proteins (YFPs) have the longest wavelength emissions of all GFP
      variants examined to date. This shift in the spectrum is the result of a T203Y
      substitution (single-letter amino acid code), a mutation rationally designed on
      the basis of the X-ray structure of GFP S65T. RESULTS: We have determined the
      crystal structures of YFP T203Y/S65G/V68L/S72A and YFP H148G to 2.5 and 2.6 A
      resolution, respectively. Both structures show clear electron density for nearly
      coplanar pi-pi stacking between Tyr203 and the chromophore. The chromophore has
      been displaced by nearly 1 A in comparison to other available structures.
      Although the H148G mutation results in the generation of a solvent channel to the
      chromophore cavity, intense fluorescence is maintained. The chromophore in the
      intact protein can be titrated, and the two variants have pKa values of 7.0 (YFP)
      and 8.0 (YFP H148G). CONCLUSIONS: The observed red shift of the T203Y YFP variant
      is proposed to be mainly due to the additional polarizability of the pi-stacked
      Tyr203. The altered location of the chromophore suggests that the exact positions
      of nearby residues are not crucial for the chemistry of chromophore formation.
      The YFPs significantly extend the pH range over which GFPs may be employed as pH
      indicators in live cells.

PMID- 9782053
TI  - Exploration of metal ion binding sites in RNA folds by Brownian-dynamics
      simulations.
AB  - BACKGROUND: Metal ions participate in the three-dimensional folding of RNA and
      provide active centers in catalytic RNA molecules. The positions of metal ions
      are known for a few RNA structures determined by X-ray crystallography. In
      addition to the crystallographically identified sites, solution studies point to
      many more metal ion binding sites around structured RNAs. Metal ions are also
      present in RNA structures determined by nuclear magnetic resonance (NMR)
      spectroscopy, but the positions of the ions are usually not revealed. RESULTS: A
      novel method for predicting metal ion binding sites in RNA folds has been
      successfully applied to a number of different RNA structures. The method is based
      on Brownian-dynamics simulations of cations diffusing under the influence of
      random Brownian motion within the electrostatic field generated by the static
      three-dimensional fold of an RNA molecule. In test runs, the crystallographic
      positions of Mg2+ ions were reproduced with deviations between 0.3 and 2.7 A for
      several RNA molecules for which X-ray structures are available. In addition to
      the crystallographically identified metal ions, more binding sites for cations
      were revealed: for example, tRNAs were shown to bind more than ten Mg2+ ions in
      solution. Predictions for metal ion binding sites in four NMR structures of RNA
      molecules are discussed. CONCLUSIONS: The successful reproduction of
      experimentally observed metal ion binding sites demonstrates the efficiency of
      the prediction method. A promising application of the method is the prediction of
      cation-binding sites in RNA solution structures, determined by NMR.

PMID- 9782052
TI  - Structure of human cyclin-dependent kinase inhibitor p19INK4d: comparison to
      known ankyrin-repeat-containing structures and implications for the dysfunction
      of tumor suppressor p16INK4a.
AB  - BACKGROUND: The four members of the INK4 gene family (p16(INK4a), p15(INK4b),
      p18(INK4c) and p19(INK4d)) inhibit the closely related cyclin-dependent kinases
      CDK4 and CDK6 as part of the regulation of the G1-->S transition in the cell
      division cycle. Loss of INK4 gene product function, particularly that of
      p16(INK4a), is found in 10-60% of human tumors, suggesting that broadly
      applicable anticancer therapies might be based on restoration of p16(INK4a) CDK
      inhibitory function. Although much less frequent, defects of p19(INK4d) have also
      been associated with human cancer (osteosarcomas). The protein structures of some
      INK4 family members, determined by nuclear magnetic resonance (NMR) spectroscopy
      and X-ray techniques, have begun to clarify the functional role of p16(INK4a) and
      the dysfunction introduced by the mutations associated with human tumors.
      RESULTS: The crystal structure of human p19(INK4d) has been determined at 1.8 A
      resolution using multiple isomorphous replacement methods. The fold of p19(INK4d)
      produces an oblong molecule comprising five approximately 32-residue ankyrin-like
      repeats. The architecture of the protein demonstrates the high structural
      similarity within the INK4 family. Comparisons to other ankyrin-repeat-containing
      proteins (GABPbeta, 53BP2 and myotrophin) show similar structures with comparable
      hydrogen-bonding patterns and hydrophobic interactions. Such comparisons
      highlight the splayed beta-loop geometry that is specific to INK4 inhibitors.
      This geometry is the result of a modified ankyrin structure in the second repeat.
      CONCLUSIONS: Among the INK4 inhibitors, the highest amino acid sequence
      conservation is found in the helical stacks; this conservation creates a
      conserved beta-loop geometry specific to INK4 inhibitors. Therefore, in addition
      to models which predict that the conserved helix alpha6 is responsible for CDK
      inhibition, a binding mode whereby the loops of INK4 proteins bind to the CDKs
      should also be considered. A similar loop-based interaction is seen in the
      complex formed between the ankyrin-repeat-containing protein GABPbeta
      and_GABPalpha. This mode of binding would be consistent with the observation that
      p16(INK4a) is sensitive to deleterious mutations found throughout this tumor
      suppressor protein; these mutations probably destabilize the three-dimensional
      structure.

PMID- 9782054
TI  - The crystal structure of nitrophorin 4 at 1.5 A resolution: transport of nitric
      oxide by a lipocalin-based heme protein.
AB  - BACKGROUND: Nitrophorins are nitric oxide (NO) transport proteins from the saliva
      of blood-feeding insects, which act as vasodilators and anti-platelet agents.
      Rhodnius prolixus, an insect that carries the trypanosome that causes Chagas'
      disease, releases four NO-loaded nitrophorins during blood feeding, whereupon the
      ligand is released into the bloodstream or surrounding tissue of the host.
      Histamine, a signaling molecule released by the host upon tissue damage, is
      tightly bound by the nitrophorins; this may facilitate the release of NO and
      reduce inflammation in the host. RESULTS: Recombinant nitrophorin 4 (NP4) was
      expressed in Escherichia coli, reconstituted with heme, and found to bind NO and
      histamine in a manner similar to that of the natural protein. The crystal
      structure of NP4 revealed a lipocalin-like eight-stranded beta barrel, with heme
      inserted into one end of the barrel. His59 ligates the proximal site on the heme,
      a solvent molecule (NH3) ligates the distal site, and three additional solvent
      molecules occupy the distal pocket. Buried in the protein interior are Glu55 and
      three solvent molecules. A detailed comparison with other lipocalins suggests
      that NP4 is closely related to the biliverdin-binding proteins from insects.
      CONCLUSIONS: The nitrophorins have a unique hemoprotein structure and are
      completely unlike the globins, the only other hemoproteins designed to transport
      dissolved gases. Compared with the recently described structure of NP1, the NP4
      structure is considerably higher resolution, confirms the unusual placement of
      ionizable groups in the protein interior, and clarifies the solvent arrangement
      in the distal pocket. It also provides a striking example of structural homology
      where sequence homology is minimal.

PMID- 9782055
TI  - The 1.8 A crystal structure of the ycaC gene product from Escherichia coli
      reveals an octameric hydrolase of unknown specificity.
AB  - BACKGROUND: The ycaC gene comprises a 621 base pair open reading frame in
      Escherichia coli. The ycaC gene product (ycaCgp) is uncharacterized and has no
      assigned function. The closest sequence homologs with an assigned function belong
      to a family of bacterial hydrolases that catalyze isochorismatase-like reactions,
      but these have only low sequence similarity to ycaCgp (approximately 20% amino
      acid identity). The ycaCgp was obtained and identified during crystallization
      trials of an unrelated E. coli protein with which it co-purified. RESULTS: The
      1.8 A crystal structure of ycaCgp reveals an octameric complex comprised of two
      tetrameric rings. A large three-layer (alphabetaalpha) sandwich domain and a
      small helical domain form the folded structure of the monomeric unit. Comparisons
      with sequence and structure databases suggest that ycaCgp belongs to a diverse
      family of bacterial hydrolases. The most closely related three-dimensional
      structure is that of the D2 tetrameric N-carbamoylsarcosine amidohydrolase
      (CSHase) from an Arthrobacter species. A conspicuous cleft between two ycaCgp
      subunits contains several conserved residues including Cys118, which we propose
      to be catalytic. In the active site, a nonprolyl cis peptide bond precedes Val114
      and coincides with a cis peptide bond in CSHase in a region of dissimilar
      sequence. The crystal structure reveals a probable error or mutation relative to
      the reported genomic sequence. CONCLUSIONS: Although the specific function of
      ycaCgp is not yet known, structural studies solidify the relationship of this
      protein to other hydrolases and illuminate its active site and key elements of
      the catalytic mechanism.

PMID- 9782056
TI  - The three-dimensional structure of a type I module from titin: a prototype of
      intracellular fibronectin type III domains.
AB  - BACKGROUND: Titin is a huge protein ( approximately 3 MDa) that is present in the
      contractile unit (sarcomere) of striated muscle and has a key role in muscle
      assembly and elasticity. Titin is mainly composed of two types of module (type I
      and II). Type I modules are found exclusively in the region of titin localised in
      the A band, where they are arranged in a super-repeat pattern that correlates
      with the ultrastructure of the thick filament. No structure of a titin type I
      module has been reported so far. RESULTS: We have determined the structure of a
      representative type I module, A71, using nuclear magnetic resonance (NMR)
      spectroscopy. The structure has the predicted fibronectin type III fold. Titin
      specific conserved residues are either located at the putative module-module
      interfaces or along one side of the protein surface. Several proline residues
      that contribute to two stretches in a polyproline II helix conformation are
      solvent-exposed and line up as a continuous ribbon extending over more than two
      thirds of the module surface. Homology models of the type I module N-terminal to
      A71 (A70) and the double module A70-A71 were used to discuss possible intermodule
      interactions and their role in module-module orientation. CONCLUSIONS: As
      residues at the module-module interfaces are highly conserved, we speculate that
      similar interactions govern all of the interfaces between type I modules in
      titin. This conservation would lead to a regular multiple array of similar
      surface structures. Such an arrangement would allow arrays of contiguous type I
      modules to expose multiple proline stretches in a highly regular way and these
      may act as binding sites for other thick filament proteins.

PMID- 9782057
TI  - Crystal structure of the phosphatidylethanolamine-binding protein from bovine
      brain: a novel structural class of phospholipid-binding proteins.
AB  - BACKGROUND: Phosphatidylethanolamine-binding protein (PEBP) is a basic protein
      found in numerous tissues from a wide range of species. The screening of gene and
      protein data banks defines a family of PEBP-related proteins that are present in
      a variety of organisms, including Drosophila and inferior eukaryotes. PEBP binds
      to phosphatidylethanolamine and nucleotides in vitro, but its biological function
      in vivo is not yet known. The expression of PEBP and related proteins seems to be
      correlated with development and cell morphogenesis, however. To obtain new
      insights into the PEBP family and its potential functions, we initiated a
      crystallographic study of bovine brain PEPB. RESULTS: The X-ray crystal structure
      of bovine brain PEBP has been solved using multiple isomorphous replacement
      methods, and refined to 1.84 A resolution. The structure displays a beta fold and
      exhibits one nonprolyl cis peptide bond. Analysis of cavities within the
      structure and sequence alignments were used to identify a putative ligand-binding
      site. This binding site is defined by residues of the C-terminal helix and the
      residues His85, Asp69, Gly109 and Tyr119. This site also corresponds to the
      binding site of phosphorylethanolamine, the polar head group of
      phosphatidylethanolamine. CONCLUSIONS: This study shows that PEBP is not related
      to the G-protein family nor to known lipid-binding proteins, and therefore
      defines a novel structural family of phospholipid-binding proteins. The PEBP
      structure contains no internal hydrophobic pocket, as described for lipocalins or
      small phospholipid-transfer proteins. Nevertheless, in PEBP, a small cavity close
      to the protein surface has a high affinity for anions, such as phosphate and
      acetate, and also phosphorylethanolamine. We suggest that this cavity corresponds
      to the binding site of the polar head group of phosphatidylethanolamine.

PMID- 9782058
TI  - Structural model of phospholipid-reconstituted human transferrin receptor derived
      by electron microscopy.
AB  - BACKGROUND: The transferrin receptor (TfR) regulates the cellular uptake of serum
      iron. Although the TfR serves as a model system for endocytosis receptors,
      neither crystal structure analysis nor electron microscopy has yet revealed the
      molecular dimensions of the TfR. To derive the first molecular model, we analyzed
      purified, lipid-reconstituted human TfR by high-resolution electron microscopy.
      RESULTS: A structural model of phospholipid-reconstituted TfR was derived from 72
      cryo-electron microscopic images. The TfR dimer consists of a large extracellular
      globular domain (6.4 x 7.5 x 10.5 nm) separated from the membrane by a thin
      molecular stalk (2.9 nm). A comparative protein sequence analysis suggests that
      the stalk corresponds to amino acid residues 89-126. Under phospholipid
      reconstitution conditions, the human TfR not only integrates into vesicles, but
      also forms rosette-like structures called proteoparticles. Scanning transmission
      electron microscopy revealed an overall diameter of 31.5 nm and a molecular mass
      of 1669 +/- 26 kDa for the proteoparticles, corresponding to nine TfR dimers. The
      average mass of a single receptor dimer was determined as being 186 +/- 4 kDa.
      CONCLUSIONS: Proteoparticles resemble TfR exosomes that are expelled by sheep
      reticulocytes upon maturation. The structure of proteoparticles in vitro is thus
      interpreted as being the result of the TfR's strong self-association potential,
      which might facilitate the endosomal sequestration of the TfR away from other
      membrane proteins and its subsequent return to the cell surface within tubular
      structures. The stalk is assumed to facilitate the tight packing of receptor
      molecules in coated pits and recycling tubuli.

PMID- 9782059
TI  - Bicelles: a model membrane system for all seasons?

PMID- 9782060
TI  - Single potassium ion seeks open channel for transmembrane travels: tales from the
      KcsA structure.
AB  - Potassium channels selectively catalyze potassium transport across cell
      membranes. Over the past five decades, a multitude of potassium channel models
      have been proposed. The recent crystal structure determination of the KcsA
      potassium channel confirms, corrects and expands our understanding of a
      fundamental biological catalyst, revealing the basis of exquisite selectivity and
      near diffusion-limited throughput.

PMID- 9782062
TI  - INDUCTION OF DIFFERENTIATION BY IL-6-TYPE CYTOKINES IS IMPAIRED IN MYELOID
      LEUKAEMIA CELLS UNABLE TO ACTIVATE Stat5a.

PMID- 9782064
TI  - Modern concepts in the therapy of urinary tract (kidney, ureter, bladder and
      prostate) tumours.

PMID- 9782065
TI  - Serial changes of soluble endothelin-1 levels during myocardial ischaemia
      reperfusion. Effects of magnesium, diltiazem and a novel MAC-1 inhibitor.
AB  - The key role of endothelin-1 (ET-1) has been recognised in patients with
      ischaemic heart disease. However, the serial changes of ET-1 during both brief
      and prolonged ischaemia-reperfusion are poorly known. Serial changes of plasma ET
      1 were measured during myocardial stunning (MS) and acute myocardial infarction
      (AMI). The effects of magnesium (Mg), diltiazem and a MAC-1 inhibitor on the
      plasma ET-1 were elucidated. Forty-nine swine underwent brief (8 min) or
      prolonged (50 min) coronary artery occlusion followed by reperfusion. ET-1 plasma
      concentration was measured by ELISA at prespecified time points. The occlusion
      was associated with a decline of ET-1 followed by a significant increase during
      the reperfusion. Mg as well as diltiazem similarly affected the plasma ET-1 by
      reducing ET-1 release during the first hour of the reperfusion period. MAC-1
      inhibition was also associated with decreases of ET-1. Ability of Mg, diltiazem
      and leumedins to decrease the ET-1 plasma level may have direct clinical
      implications for the use of these agents in patients with coronary artery
      disease.

PMID- 9782066
TI  - Effects of WEB 2086 on the protective role of preconditioning against arrhythmias
      in rats.
AB  - The purpose of the present study was to investigate a possible role of platelet
      activating factor (PAF) in ischaemic preconditioning (PC). Since both PC and PAF
      act through protein kinase C (PKC), PAF could play a role in PC. To test this
      hypothesis, anaesthetized, open-chest male rats were subjected to four different
      protocols. Group I was subjected to 30 min of left coronary artery occlusion. In
      Group II, WEB 2086 (10 mg kg-1 i.v. bolus+1 mg kg-1 h-1 i.v. infusion) a
      selective PAF antagonist was given to non-preconditioned rats 23 min before the
      30-min occlusion period. In Group III and IV ischaemic PC was elicited by one
      cycle of 3 min occlusion and 5 min reperfusion and also in Group IV, WEB 2086 (10
      mg kg-1 i.v. bolus+1 mg kg-1 h-1 i.v. infusion) was given 23 min before the 30
      min occlusion period. Ventricular ectopic beats (VEB), ventricular tachycardia
      (VT), and ventricular fibrillation (VF) that occurred during 30 min occlusion
      were determined. WEB 2086 administration or PC reduced the VEBs significantly.
      Incidence of VT and VF were not affected by WEB 2086 compared with control
      values, although PC decreased the incidence of VT and VF. WEB 2086 administration
      did not attenuate PC-induced improvement of arrhythmia parameters. These data
      demonstrated that a specific PAF antagonist, WEB 2086 did not abolish PC-induced
      protection against arrhythmias.

PMID- 9782067
TI  - Influence of baseline values on lipids and lipoprotein changes during amlodipine
      treatment of hypertension.
AB  - Twenty adult hypertensive patients classified as having 'low', 'medium' and
      'high' baseline values, underwent plasma lipids and lipoproteins assessment after
      12 weeks treatment with amlodipine. For the patients with low baseline values,
      the mean triglycerides and very low density lipoprotein-cholesterol levels
      increased after amlodipine therapy. No significant variation was observed in the
      mean values of the lipids and lipoproteins before and after amlodipine therapy
      for the patients with 'medium baseline values', while in patients with 'high
      baseline values', mean low density lipoprotein-cholesterol decreased after
      amlodipine therapy. These findings therefore suggest that the levels of the
      baseline lipid and lipoprotein profiles may have a significant influence on the
      lipid altering actions of amlodipine pharmacotherapy.

PMID- 9782068
TI  - The effects of potassium channel modulators on the simulated ischaemia-induced
      changes in contractility and responsiveness to phenylephrine of rat-isolated
      papillary muscle.
AB  - The aim of the present study was to compare the influence of terikalant, a
      blocker of inwardly rectifying K+ channels, galanin, a neuropeptide of 29
      aminoacids with a complex mechanism of action including an activation of inwardly
      rectifying K+ channels and glibenclamide, a blocker of ATP-sensitive K+ channels,
      on simulated ischaemia-induced changes in contractility and response to
      phenylephrine of rat-isolated heart muscle. Experiments were performed on
      isolated rat heart papillary muscles. The following parameters were measured:
      force of contraction (Fc), velocity of contraction (+dF/dt) and velocity of
      relaxation (-dF/dt), time to peak contraction (ttp) and relaxation time at 10% of
      total amplitude of contraction (tt10). In the presence of 1 microM of galanin, as
      well as terikalant, simulated ischaemia caused a decrease in Fc, +dF/dt and 
      dF/dt, however, it significantly increased a drop in Fc and -dF/dt. After 60 min
      of reperfusion, all the measured parameters recovered completely except Fc in the
      galanin group. Terikalant, but not galanin, prevents the negative inotropic
      action of phenylephrine observed in the control group. On the other hand,
      addition of 1 microm of glibenclamide to the no-substrate solution prevented the
      simulated ischaemia-induced decrease in Fc, +dF/dt and -dF/dt. In this group
      phenylephrine did not cause the negative inotropic action. The above mentioned
      data reveal that pretreatment with the inhibitors of ATP-sensitive and inwardly
      rectifying K+ channels protect rat-isolated papillary muscle against ischaemia
      induced disturbances in contractility.

PMID- 9782069
TI  - Pharmacological profiles of SKP-450 and its family, a K+ channel opener, in
      comparison with levcromakalim.
AB  - This study was carried out to characterise the vasodepressor and vasorelaxant
      actions of a benzopyran derivative, SKP-450 and its family, (+/-)-racemate SKP
      411, (+)-enantiomer SKP-451, and the metabolites of SKP-450 (SKP-818 and SKP-310)
      in comparison with levcromakalim (LCRK) in the canine coronary, rabbit basilar
      and vertebral arterial segments. SKP-450, its family (SKP-411 and SKP-451) and
      the metabolite of SKP-450 (SKP-818) caused concentration-dependent relaxations as
      well as LCRK in the canine coronary artery and rabbit basilar and vertebral
      arteries. The relaxant potency of SKP-450 was significantly higher than that of
      LCRK in the three arteries in terms of EC50 values. SKP-450- and LCRK-induced
      vasorelaxations were competitively antagonised by glibenclamide with pA2 values
      of 7.60 (slope 1.22) and 7.99 (slope, 1.00), respectively. SKP-450 (0.1 and 1.0
      microM) caused a significant stimulation of the 86Rb efflux from canine coronary
      arteries in a concentration-dependent manner as well as LCRK (1 and 10 microM),
      and their effects were antagonised by glibenclamide (10 microM). SKP-450 as well
      as LCRK produced long-lasting decreases in mean arterial pressure in the
      spontaneously hypertensive rats (SHR). These results suggest that SKP-450 has a
      significantly higher potency than LCRK in in vitro vasorelaxation, and it exerts
      potent and long-lasting vasodepressor effects with its active metabolite (SKP
      818).

PMID- 9782071
TI  - Alterations in superoxide dismutase activities, lipid peroxidation and
      glutathione levels in thinner inhaled rat lungs: relationship between
      histopathological properties.
AB  - Paint thinner has widespread use in industry. The use of thinner among children
      as a narcotic agent has become a social and health problem. There is some
      evidence that organic solvents may express their toxicity by the way of reactive
      oxygen species (ROS) induced cell damage. ROS has been shown to induce lipid
      peroxidation in biological membranes. This study examined peroxidative and
      histopathological changes in the rat lung, during 5 weeks of thinner inhalation.
      Significant increases were found in lipid peroxidation (MDA+4-DHA) levels related
      to the duration of inhalation. As opposed to increases in the lipid peroxidation
      levels, significant decreases in superoxide dismutase activities and glutathione
      levels were observed from the third inhalation week to the end of the fifth week.
      At the beginning of the inhalation slight inflammatory changes, intraalveolar and
      interstitial extravasation and oedema in lung parenchyma were noted. As the
      inhalation period extended, chronic inflammatory changes, alveolar epithelial
      proliferation, collapse, emphysematous changes and interstitial fibrosis in lung
      were detected.

PMID- 9782070
TI  - The role of l-thyroxine and hepatic reductase activity in isoniazid-induced
      hepatotoxicity in rabbits.
AB  - There is evidence that hydrazine, a metabolite of isoniazid, plays an important
      role in the mechanism of isoniazid-induced hepatotoxicity. Hydrazine has been
      reported to be metabolised by NADPH cytochrome P-450 reductase (reductase) to
      reactive and potentially toxic intermediates. The present study was designed,
      using a model of isoniazid-induced hepatotoxicity in rabbits, to determine
      whether or not reductase plays a role in this toxicity. Although pretreating
      rabbits with l-thyroxine increased hepatic reductase activity (54% greater than
      controls), the severity of isoniazid-induced hepatic cell damage (plasma
      argininosuccinic acid lyase activity) was lower in thyroxine pre-treated animals
      than in animals treated with isoniazid alone (31.3+/-20 vs 56.0+/-20 Takahara
      Units, respectively). In addition, pre-treatment with l-thyroxine completely
      prevented isoniazid-induced hepatic steatosis. In conclusion, contrary to our
      hypothesis, an increase in reductase activity achieved by pre-treatment with l
      thyroxine was associated with a decrease in the severity of isoniazid-induced
      hepatic cell damage and steatosis in rabbits.

PMID- 9782072
TI  - An assessment of the potential of protopine to inhibit microsomal drug
      metabolising enzymes and prevent chemical-induced hepatotoxicity in rodents.
AB  - The potential of protopine to inhibit microsomal drug metabolising enzymes (MDM
      E) and prevent paracetamol- and CCl4-induced hepatotoxicity was studied in rats.
      Paracetamol at the dose of 640 mg kg-1 produced hepatic damage in rats as
      manifested by the rise in serum levels of aspartate transaminase (AST) and
      alanine transaminase (ALT) to 972+/-186 and 624+/-131 IU (mean+/-sem; n=10),
      respectively, compared to respective control values of 101+/-29 and 64+/-18 IU.
      Pretreatment of rats with protopine (11 mg kg-1, orally twice daily for 2 days)
      lowered significantly the respective serum AST and ALT levels (P<0.05) to 289+/
      52 and 178+/-43 IU. The hepatotoxic dose of CCl4 (1.5 ml kg-1; orally) raised
      serum AST and ALT levels to 543+/-89 and 387+/-69 IU (mean+/-sem; n=10),
      respectively, compared to respective control values of 98+/-28 and 56+/-17 IU.
      The same dose of protopine (11 mg kg-1) was able to prevent significantly
      (P<0.05), the CCl4-induced rise in serum enzymes and the estimated values of AST
      and ALT were 168+/-36 and 93+/-28 IU, respectively. Protopine caused prolongation
      (P<0.05) in pentobarbital (55 mg kg-1)-induced sleep as well as potentiated
      strychnine-induced toxicity in rats, suggestive of an inhibitory effect on MDME.
      These results indicate that protopine exhibits anti-hepatotoxic action which may
      be mediated through inhibition of MDME.

PMID- 9782073
TI  - Involvement of DA1 and DA2 receptors in the gastroprotective activity of amylin
      in the rat.
AB  - Peripheral administration of amylin (40 microg kg-1) exerts gastroprotective
      effects in the reserpine-induced gastric lesions in the rat. This activity is
      decreased by pretreatment (30 min before) with (-)-sulpiride (0.1 mg kg-1 s.c.)
      or domperidone (0.1-2.5 mg kg-1 per os), dopamine DA2 antagonists. Pretreatment
      with SCH 23390 (0.5-4 mg kg-1 s.c.), a DA1 antagonist, at the maximal dose used,
      also significantly decreased the gastroprotective activity of the peptide. Amylin
      does not exert any gastroprotective effect in indomethacin-pretreated rats (7.5
      mg kg-1 s.c., 30 min before), as well as in the aspirin-induced ulcer test (200
      mg kg-1 per os at the time of amylin administration). Our data confirm that the
      gastroprotective effect of amylin in reserpine-induced gastric lesions involves,
      at least in part, the dopaminergic transmission, interfering with both the DA1
      and DA2 receptor subtypes.

PMID- 9782074
TI  - Effects of L-histidinol on the antitumour activity and acute cardiotoxicity of
      doxorubicin in mice.
AB  - L-Histidinol (LHL), a structural analogue of the essential amino acid l
      histidine, can improve the therapeutic index of antimetabolites and alkylating
      agents. The objective of the study was to determine whether LHL would modulate
      the antitumour activity and acute cardiotoxicity of the anthracycline antibiotic,
      doxorubicin (DOX). LHL (1.0 mM) potentiated the cytotoxicity of DOX (0.05-0.8
      microg ml-1) in cultured Ehrlich ascites carcinoma (EAC) cells. LHL (250 mg kg-1,
      i.p.) administered for five consecutive doses at 2-h intervals starting 2 h
      before DOX (5 mg kg-1, i.p.) single injection, enhanced the antitumour activity
      of DOX in EAC-bearing mice as manifested by a significant increase in average
      life span and cure rate of mice. In normal mice, LHL, in the same dose regimen,
      could not alter the acute cardiotoxicity and lethality of DOX (10 mg kg-1, i.p.).
      The present data indicate that LHL may improve the therapeutic efficacy of DOX in
      EAC-bearing mice without compromising its toxicity. Also, our finding supports
      the LHL/anticancer drug combination approach.

PMID- 9782075
TI  - Pharmacologic study of 3-hour 135 mg M-2 paclitaxel in platinum pretreated
      patients with advanced ovarian cancer.
AB  - Paclitaxel (Taxol(R)) is an active agent in platinum-refractory ovarian cancer.
      Since the available pharmacokinetic data of 135 mg m-2 paclitaxel administered by
      3-h infusion are scarce and fragmented, we now describe a comprehensive
      pharmacologic study in a group of 13 patients who were pretreated with platinum
      for advanced ovarian cancer. The mean paclitaxel AUC was 10.3+/-2.4 h micromol l
      1 (range 6.8-13.9 h micromol l-1). Quantification of the two major paclitaxel
      metabolites, 6alpha-hydroxypaclitaxel and 3'-p-hydroxypaclitaxel yielded AUCs of
      0.44+/-0.30 h micromol l-1 and 0.31+/-0.20 h micromol l-1, respectively. The AUC
      of 3'-p-hydroxypaclitaxel was significantly different from that of patients with
      an altered hepatic function. The administration of 135 mg m-2 single-paclitaxel
      was safe, and the toxicities observed at higher doses in earlier studies were
      absent in this study. This is important, because the schedule and paclitaxel dose
      of 135 mg m-2 given by a 3-h infusion is expected to be used more frequently in
      combination with other cytotoxic agents with the aim of improving efficacy.

PMID- 9782076
TI  - A second mammalian antizyme: conservation of programmed ribosomal frameshifting.
AB  - A second mammalian ornithine decarboxylase antizyme was discovered. The deduced
      protein sequence of the human antizyme2 is 54% identical and 67% similar to human
      antizyme1 but 99.5% identical to mouse antizyme2. Polyamine-regulated programmed
      ribosomal frameshifting is used in decoding antizyme2 mRNA as it is for antizyme1
      mRNA. The mRNA signals for the programmed frameshifting are similar in the mRNAs
      for the two antizymes. However, in the stimulatory pseudoknot 3' of the shift
      site, while the sequences of the stems are highly conserved, the sequences of the
      loops are divergent. Functional distinctions between antizymes seem likely, but
      no distinction in the tissue distribution of human antizyme1 and 2 mRNAs was
      distinguished, though antizyme2 mRNA is 16-fold less abundant than its antizyme1
      counterpart. In addition to the previously characterized human antizyme1 mRNA, a
      second antizyme1 mRNA with an additional 160 nucleotides at its 3' end was
      identified, and it has a tissue distribution different from that of the shorter
      antizyme1 mRNA.

PMID- 9782077
TI  - A novel human gene FKBP6 is deleted in Williams syndrome.
AB  - Williams syndrome (WS) is a developmental disorder caused by haploinsufficiency
      of genes at 7q11.23. We have shown that hemizygosity of elastin is responsible
      for one feature of WS, supravalvular aortic stenosis. We have also implicated LIM
      kinase 1 hemizygosity as a contributing factor to impaired visual-spatial
      constructive cognition in WS. Here we identify and characterize a novel gene,
      FKBP6, within the common WS deletion region. FKBP6 shows homology to the FK-506
      binding protein (FKBP) class of immunophilins. FKBP6 has a putative N-terminal FK
      506 binding and peptidylproyl isomerase (rotamase) domain and, like known high
      molecular-weight FKBPs, an imperfect C-terminal tetratricopeptide repeat domain.
      FKBP6 is expressed in testis, heart, skeletal muscle, liver, and kidney. FKBP6
      consists of nine exons and is completely contained within a 35-kb cosmid clone.
      Fluorescence in situ hybridization experiments show that FKBP6 gene is deleted in
      40/40 WS individuals. Hemizygous deletion of FKBP6 may contribute to certain
      defects such as hypercalcemia and growth delay in WS.

PMID- 9782078
TI  - Strategy to sequence the 89 exons of the human LRP1 gene coding for the
      lipoprotein receptor related protein: identification of one expressed mutation
      among 48 polymorphisms.
AB  - The human lipoprotein receptor related protein (LRP) binds and internalizes a
      diverse set of ligands, making LRP the most multifunctional endocytic receptor
      known. This is possible due to the large size, i.e., 600 kDa, of the receptor
      protein containing three clusters of putative ligand binding domains, each
      structurally comparable to the classical LDL receptor. Based on previous
      structural analysis of the human LRP1 gene (Van Leuven et al., 1994, Genomics,
      24: 78-89), a strategy was developed to sequence the 89 exons of the LRP1 gene,
      including partial intron sequences. The gene was amplified from individual
      genomic DNA by long-range PCR, in 14 amplicons sized between 0.4 and 11 kb that
      were used as templates for 110 sequencing primers. In total, 48 mutations and
      intronic polymorphisms were identified. Two previously reported polymorphisms,
      i.e., in the promoter region and in exon 3, were precisely defined by sequencing.
      The first expressed mutation, i.e., an alanine to valine transition at position
      217 of the LRP precursor protein, was detected on one allele in 2 of 33
      individuals. Although the strategy is still subject to refinement, this approach
      is reported to allow others to analyze genetic differences in the human LRP1
      gene, with particular reference to the recently reported association with late
      onset Alzheimer disease.

PMID- 9782079
TI  - Analysis of the human LRPAP1 gene coding for the lipoprotein receptor-associated
      protein: identification of 22 polymorphisms and one mutation.
AB  - The lipoprotein receptor-associated protein (RAP) is considered a chaperone
      protein for the lipoprotein receptor-related protein (LRP) and for the other
      members of the LDL receptor family. Genetic analysis is anticipated to help in
      delineating groups or individuals with potential defects or problems in this
      regard. A combined amplification/sequencing strategy was developed to analyze the
      human LRPAP1 gene for polymorphisms and mutations. The LRPAP1 gene was amplified
      from genomic DNA in four long-range PCR amplicons, 2.4 to 7.6 kb in size. Three
      amplicons were finally used as templates with 14 sequencing primers to obtain the
      sequence of the eight exons and large portions of adjacent introns from
      individual DNA. This strategy, applied to sequence the LRPAP1 gene of 14
      unrelated, normal individuals revealed, in total, 23 distinct mutations and
      polymorphisms, mostly intronic substitutions and deletions. In this small group 1
      expressed mutation was encountered on one allele in 2 unrelated individuals: a G
      to A transition results in the replacement of valine by methionine in exon 7 at
      position 311 of the human RAP precursor protein.

PMID- 9782081
TI  - The human hypoxia-inducible factor 1alpha gene: HIF1A structure and evolutionary
      conservation.
AB  - The HIF1A gene encodes the HIF-1alpha subunit of hypoxia-inducible factor 1, a
      transcription factor that is essential for cardiovascular development and
      systemic O2 homeostasis. HIF1A consists of 15 exons that are interrupted by
      introns at the same locations as in the mouse Hif1a gene, although sequences
      mediating alternative splicing and alternative translation initiation events in
      the mouse are not present in the human gene. Placement of introns differs between
      HIF1A and EPAS1, which encodes the human HIF-2alpha protein. Transcription of the
      HIF1A gene was initiated over a 15-nt region downstream of two SP1 sites. A 0.7
      kb region of 5' flanking sequences functioned as a strong promoter in transient
      expression assays. Comparison of 0.8 kb of 5' flanking and 5' untranslated
      sequences from the HIF1A and Hif1a genes revealed 70% identity. The proximal 300
      bp of 5' flanking sequences was 83% identical, including the SP1 sites and
      transcription initiation sites. These results suggest evolutionary selection for
      maintenance of HIF1A structure, function, and regulation.

PMID- 9782080
TI  - Three murine cataract mutants (Cat2) are defective in different gamma-crystallin
      genes.
AB  - A number of murine cataract mutations have been localized to chromosome 1 close
      to the gamma-crystallin gene cluster (Cryg) (Everett et al., 1994, Genomics 20:
      429-434; Loster et al., 1994, Genomics 23: 240-242). Based on the size of the
      mapping or allelism tests they have not been shown to be genetically distinct and
      have been assigned to locus symbol Cat2. Here we assign three mutations to the
      respective gamma-crystallin gene. Using a systematic candidate gene approach to
      analyze the entire Cryg cluster, an A-->G transition was found in exon 2 of Cryga
      for the ENU-436 mutation and is designated Cryga1Neu. The mutant allele Crygbnop
      (formerly Cat2(nop)) is caused by a replacement of 11 bp by 4 bp in the third
      exon of Crygb, while a C-->G transversion in exon 3 of Cryge has been found for
      the Cryget (formerly Cat2(t)) mutation. For the mutation Cryga1Neu, an Asp-->Gly
      exchange is deduced, whereas the mutations Crygbnop and Cryget lead to the
      formation of in-frame stop codons and give rise to truncated proteins of 144 and
      143 amino acids, respectively. The effects of the mutations upon gamma-crystallin
      structure are likely to be quite different. The Cryga1Neu mutation is expected to
      affect the link between Greek-key motifs 2 and 3, whereas both Crygbnop and
      Cryget mutations are supposed to truncate the fourth Greek-key motif. All three
      mutations are predicted to alter protein folding of the gamma-crystallins and
      result in lens cataract, but the phenotype for each is quite distinctive.

PMID- 9782082
TI  - Informative genetic polymorphic markers within the centromeric regions of human
      chromosomes 17 (D17S2205) and 11 (D11S4975).
AB  - We have taken advantage of the presence of retrotransposed L1 elements within the
      centromeric alphoid sequences of the human genome to characterize polymorphic
      markers at the centromeres of human chromosomes 17 and 11 (D17S2205 and D11S4975,
      respectively). They correspond to microsatellites found at the 3' ends of L1
      elements inserted within the alpha satellite sequences of the two chromosomes.
      They were detected after PCR by direct analysis in sequencing gels. Eight and
      five alleles, respectively, were found with heterozygosities of 0.67 and 0.68.
      They were converted into STSs by designing primers specific for each. D17S2205
      and D11S4975 can be used as genuine anchor-informative genetic points for
      chromosomes 17 and 11. Both markers have been placed on the available genetic
      maps of their centromeric regions. The alphoid domain within which D17S2205 is
      embedded is ancestral to the canonical ones on chromosome 17 that exhibit several
      haplotypes in present-day human populations.

PMID- 9782084
TI  - Cloning and localization of a human diphthamide biosynthesis-like protein-2 gene,
      DPH2L2.
AB  - Sequence analysis of the candidate tumor suppressor OVCA1 revealed extensive
      sequence identity and similarity to proteins from a diverse number of species,
      including the yeast diphthamide biosynthesis protein-2, dph2, which suggested
      that OVCA1 may be the human homologue to this yeast gene. However, searches of
      the translated EST database for sequences in common with dph2 and OVCA1 uncovered
      an EST, h52976, with significant amino acid conservation with dph2. Isolation of
      a cDNA clone encompassing the EST by RACE methodologies and sequence analysis
      indicate the identification of a previously unidentified gene that is
      ubiquitously expressed and maps to chromosome 1p34. Based on amino acid sequence
      analysis, the 489-amino-acid protein encoded by this novel gene is distinct from
      OVCA1 and is more closely related to the yeast dph2 gene product. Therefore, we
      refer to this novel gene as DPH2L2, which constitutes one member of a novel gene
      family that may be involved in diphthamide biosynthesis in humans.

PMID- 9782083
TI  - Genomic organization and partial duplication of the human alpha7 neuronal
      nicotinic acetylcholine receptor gene (CHRNA7).
AB  - The human alpha7 neuronal nicotinic acetylcholine receptor gene (HGMW-approved
      symbol CHRNA7) has been characterized from genomic clones. The gene is similar in
      structure to the chick alpha7 gene with 10 exons and conserved splice junction
      positions. The size of the human gene is estimated to be larger than 75 kb. A
      putative promoter 5' of the translation start in exon 1 has been cloned and
      sequenced. The promoter region lacks a TATA box and has a high GC content (77%).
      Consensus Sp1, AP-2, Egr-1, and CREB transcription factor binding sites appear to
      be conserved between bovine and human genes. The alpha7 nAChR gene was found to
      be partially duplicated, with both loci mapping to the chromosome 15q13 region. A
      yeast artificial chromosome contig was constructed over a genetic distance of 5
      cM that includes both alpha7 loci and the region between them. Four novel exons
      are described, located in genomic clones containing the partially duplicated
      gene. The duplicated sequences, including the novel exons, are expressed in human
      brain.

PMID- 9782085
TI  - Localization of the human stat6 gene to chromosome 12q13.3-q14.1, a region
      implicated in multiple solid tumors.
AB  - Stat6 signaling pathways have been correlated with functional responses induced
      by IL-4 and PDGF that may play a role in human malignancy. Utilizing fluorescence
      in situ hybridization, we mapped the human Stat6 gene to chromosome 12q bands
      13.3-14.1, a breakpoint region implicated in a wide variety of solid tumors. To
      understand the genesis of three human Stat6 variant cDNAs, including a naturally
      occurring dominant negative species, we further characterized the genomic
      structure and flanking regions of the human Stat6 gene. The human Stat6 gene
      encompassed over 19 kb and contained 23 exons. For promoter studies, we
      introduced flanking sequence 5' of Stat6 exon 1 into a promoterless luciferase
      reporter vector and characterized basal promoter activity by deletion analysis.
      DNA sequence analysis revealed potential transcriptional regulation of the
      putative promoter through numerous consensus binding elements. Finally, we
      conclude that selective exon deletion and utilization of alternative
      donor/acceptor sites appear to explain best human Stat6 variant mRNAs.

PMID- 9782086
TI  - Restriction map of a YAC and cosmid contig encompassing the oculopharyngeal
      muscular dystrophy candidate region on chromosome 14q11.2-q13.
AB  - As part of our effort to clone positionally the oculopharyngeal muscular
      dystrophy (OPMD) gene, we constructed a YAC contig, a cosmid contig, and an EcoRI
      restriction map of the OPMD candidate region. The YAC contig spans more than 2 Mb
      and encompasses the loci D14S283 and D14S990 and the cardiac alpha and beta
      myosin heavy chain genes (MYH6 and MYH7). A 700-kb cosmid contig containing the
      D14S990 and the myosin genes and a long-range restriction map covering the region
      between D14S990 and the MYH6 and MYH7 gene cluster were established. A detailed
      EcoRI restriction map of the cosmid contig was determined, and five putative CpG
      islands were identified. Based on these data, the four loci were mapped within an
      approximately 600-kb region with the following centromere to telomere order:
      D14S283, D14S990, MYH6, and MYH7. The YAC and cosmid contigs will facilitate the
      identification of genes lying within the OPMD candidate interval.

PMID- 9782087
TI  - Cloning and mapping of the UNC5C gene to human chromosome 4q21-q23.
AB  - The vertebrate Unc5 genes, like their Caenorhabditis elegans counterpart, define
      a family of putative netrin receptors. One member of this family, Unc5h3, has
      been shown to have an important role during cell migration in the developing
      murine cerebellum. Mice homozygous for mutations in Unc5h3 are ataxic and have
      cerebellar hypoplasia and laminar structure defects. In addition, these mice have
      ectopic granule and Purkinje cells in the midbrain and brainstem. We have
      identified the human homologue of this gene, UNC5C, and shown it to have a
      restricted expression pattern in adult human tissues. By radiation hybrid
      analysis, we have determined that UNC5C localizes to chromosome 4q21-q23 between
      markers D4S1557 and D4S836 and is closely linked to the Parkinson disease gene.

PMID- 9782088
TI  - Chromosomal localization reveals three kinesin heavy chain genes in mouse.
AB  - Kinesin-related proteins constitute a superfamily of microtubule-dependent motors
      that play important roles in organelle transport and cell division. These
      molecules share a conserved motor region of approximately 340 amino acids, which
      is attached to diverse "tail" or cargo-binding domains. The kinesin superfamily
      was first defined by kinesin heavy chain, which is the principal component of
      "true" kinesin. Invertebrates appear to possess only a single gene encoding
      kinesin heavy chain. Mammals appear to have two or more genes encoding kinesin
      heavy chain, although the precise situation has been unclear. Here we
      definitively demonstrate that mouse has three kinesin heavy chain genes, Kif5a,
      Kif5b, and Kif5c. Kif5a, Kif5b, and Kif5c map to mouse chromosomes 10, 18, and 2;
      Kif5a and Kif5c appear to be expressed only in neuronal tissues by Northern blot
      analysis while Kif5b appears to be ubiquitous in its expression.

PMID- 9782089
TI  - A YAC contig in Xq22.3-q23, from DXS287 to DXS8088, spanning the brain-specific
      genes doublecortin (DCX) and PAK3.
AB  - Although several genes for mental retardation and epilepsy, including double
      cortex/X-linked lissencephaly (DC/XLIS), have been localized to Xq21.3-q23, there
      has been no complete physical map of this region available. We constructed a
      YAC/STS contig map by initiating two yeast artificial chromosome (YAC) walks from
      the markers that flanked the DC/XLIS candidate gene region. We report an
      approximately 4-Mb contig extending from DXS287 to DXS8088, encompassing DXS1072
      and DXS1059, and composed of 52 YACs identified with 15 previously published STSs
      and 19 novel YAC-end STSs. This contig also contains two brain-specific genes,
      doublecortin (HGMW-approved symbol DCX), responsible for DC/XLIS, and PAK3, which
      may be responsible for neurological diseases localized to this region. The new
      contig extends and incorporates several previously published contigs, providing a
      total overlapping contig extending approximately 34 Mb from DXS441 in Xq13.1 to
      DXS8088 in Xq23.

PMID- 9782090
TI  - Cloning of a novel C-terminal kinesin (KIFC3) that maps to human chromosome 16q13
      q21 and thus is a candidate gene for Bardet-Biedl syndrome.
AB  - Kinesins are a large superfamily of microtubule motors that mediate specific
      motile processes. In a previous study, we identified 11 kinesin family members in
      the retina and retinal pigment epithelium (RPE) of the striped bass, Morone
      saxatilus. We have now identified, cloned, and sequenced the human homologue
      (KIFC3) of the most abundantly expressed retinal kinesin from that study, the C
      terminal kinesin FKIF2. An antibody raised against an FKIF2 peptide cross-reacted
      with an approximately 80-kDa protein in human retina, RPE, kidney, and lung.
      Since microtubule-dependent processes are critical to the function and
      morphogenesis of the photoreceptors and RPE, the abundantly expressed KIFC3 was
      considered to be a potential candidate gene for causing human retinal
      degeneration. Chromosomal localization of the KIFC3 gene revealed that it maps to
      chromosome 16q13-q21, within the critical region for a Bardet-Biedl syndrome
      locus (BBS2). Bardet-Biedl syndrome is a genetically heterogeneous, autosomal
      recessive disorder characterized by retinal dystrophy, polydactyly, obesity,
      hypogonadism, renal abnormalities, and mental retardation. The chromosomal
      localization and expression pattern of KIFC3 suggest that it may be an excellent
      candidate for families linked to BBS2.

PMID- 9782092
TI  - Gridded genomic libraries of different chordate species: a reference library
      system for basic and comparative genetic studies of chordate genomes.
AB  - The use of genomic libraries maintained in arrayed format is becoming a more and
      more popular tool for the analysis of molecular evolution and comparative
      molecular development. Being able to use already existing reference libraries
      considerably reduces the work load, and if results are made publicly available,
      it will facilitate in silica experiments in the future. Here we describe the
      construction and preliminary characterization of six cosmid libraries of
      different chordate species, Ciona intestinalis (Hemichordate), Branchiostoma
      floridae (Cephalochordate), Lampetra fluviatilis (Cyclostoma), Xiphophorus
      maculatus, and Danio rerio (Osteichthyes) in Lawrist7 and Fugu rubripes in
      Lawrist4.

PMID- 9782091
TI  - Cloning and characterization of a human and murine T-cell orphan G-protein
      coupled receptor similar to the growth hormone secretagogue and neurotensin
      receptors.
AB  - Growth hormone secretagogues (GHS) are a group of synthetic peptide and
      nonpeptide molecules that potently stimulate the release of GH from the anterior
      pituitary gland through the activation of a novel G-protein-coupled receptor (GPC
      R), the GHS-R. In our search for GHS-R family members, we recently described the
      cloning of two related GPC-Rs, GPR38 and 39. In the present report, we detail the
      isolation of a new GPC-R (FM-3) from human and mouse with moderate sequence
      identity to both the GHS-R and neurotensin-R. FM-3 is expressed in a diverse set
      of tissues.

PMID- 9782093
TI  - Asthma and bronchial hyperresponsiveness linked to the XY long arm
      pseudoautosomal region.
AB  - We examined the long arm XY pseudoautosomal region for linkage to asthma, serum
      IgE, and bronchial hyperresponsiveness. In 57 Caucasian families multipoint
      nonparametric analyses provide evidence for linkage between DXYS154 and bronchial
      hyperresponsiveness (P = 0.000057) or asthma (P = 0.00065). This genomic region
      is approximately 320 kb in size and contains the interleukin-9 receptor gene.
      These results suggest that a gene controlling asthma and bronchial
      hyperresponsiveness maybe located in this region and that the interleukin-9
      receptor is a potential candidate.

PMID- 9782094
TI  - Coding sequence and expression patterns of mouse chordin and mapping of the
      cognate mouse chrd and human CHRD genes.
AB  - Chordin is a key developmental protein that dorsalizes early vertebrate embryonic
      tissues by binding to ventralizing TGF-beta-like bone morphogenetic proteins and
      sequestering them in latent complexes. Here we report the first characterization
      of mammalian chordin. The full-length cDNA sequence for mouse chordin is given,
      and RNA blot analysis shows the murine chordin gene Chrd to be expressed at
      relatively high levels in 7-day postcoitum mouse embryos and at much decreased
      levels at later developmental times and in adult tissues. These results imply a
      major role for chordin during gastrulation of the mammalian embryo. Nevertheless,
      both murine and human chordin genes are shown to be expressed at readily
      detectable levels in several fetal and adult tissues, most notably liver and
      cerebellum, suggesting additional roles in organogenesis and homeostasis. Chrd
      was mapped to mouse chromosome 16 using interspecific crosses, and the cognate
      human gene CHRD was localized to human chromosome 3q27 by radiation hybrid
      mapping.

PMID- 9782095
TI  - Cloning and characterization of a novel human gene, TM4SF6, encoding a protein
      belonging to the transmembrane 4 superfamily, and mapped to Xq22.

PMID- 9782096
TI  - Assignment of the steroid receptor coactivator-1 (SRC-1) gene to human chromosome
      band 2p23.

PMID- 9782097
TI  - Human histone deacetylase 2, HDAC2 (Human RPD3), is localized to 6q21 by
      radiation hybrid mapping.

PMID- 9782098
TI  - Frank A. Beach Award.

PMID- 9782099
TI  - Methods, marks, and models for inferring hominid and carnivore behavior.

PMID- 9782100
TI  - Hominid phylogeny: inferences from a sub-terminal minisatellite analyzed by
      repeat expansion detection (RED).

PMID- 9782101
TI  - On the Relationship Between Evolution of Virulence and Host Demography.
AB  - The effects of density-dependence on the evolution of virulence in super
      infection models is the theme of this paper. The qualitative dynamics of three
      host-pathogen systems are studied numerically in a virulence-superinfection
      parameter landscape. It is shown numerically that pathogen's competitive
      exclusion coexistence and host population extinction depend heavily of the
      population dynamics of the host population. Reported patterns of diversity found
      using models without demography, are insufficient to account for the
      coevolutionary dynamics under defined selective pressures. Specifically,
      virulence and superinfection in the presence of a variable host population give
      rise to threshold values that divide (as switches) the regions of coexistence and
      competitive exclusion. Tight coevolution on a variable host population may occur
      within regions of parameter space that are not connected. We present our
      numerical results using a simple host-disease system where a homogeneous host
      population is invaded by two competing pathogen strains (partial analytical
      results will be published elsewhere).Copyright 1998 Academic Press Limited

PMID- 9782102
TI  - Stability with Inheritance in the Conditional Strategy.
AB  - The conditional strategy is a theoretical framework that explains the existence
      within populations of individuals that express alternative behavioral, physical
      or life history tactics (phenotypes). An example is fighters and sneakers in many
      animal mating systems. In the conditional strategy the alternative tactics are
      chosen by individuals based on their state, for example large or small bodied.
      Since state is often heritable, due for example to additive genetic variance, the
      alternative tactics may also have inheritance. As the tactics do not have equal
      fitnesses, it is generally believed that any such inheritance would prevent the
      evolutionary stability of the conditional strategy. However, in previous work we
      introduced an Inheritance Theorem and were able to prove that a conditional
      strategy with tactic inheritances can have a unique equilibrium proportion of the
      tactics. We now prove a second property of our Inheritance Theorem, namely the
      stability of the equilibrium. This means that if the tactics are perturbed from
      their equilibrium proportions, they will return across generations to their
      equilibrium proportions. An example is provided in mites. We have therefore
      established an Inheritance Theorem which includes both the existence of an
      equilibrium and its stability for alternative tactics in a conditional
      strategy.Copyright 1998 Academic Press Limited

PMID- 9782103
TI  - A Model of Phyllotaxis.
AB  - Phyllotaxis is the study of the symmetrical arrangements of plant organs, and
      most often associated with the Fibonacci series of numbers. The present work
      points out that the well known Helmholtz equation of mathematical physics
      correlates all of the well known patterns in one simple algorithm, involving two
      integers p and q: p>q>0 accounts for spiral patterns, including "jugate"
      patterns, p=q gives the alternating whorl patterns, while p>0, q=0 gives
      superposed whorls. In spiral patterns, the integers p, q underlie the larger and
      more usual integers m, n. The integer number of leaves N in a pattern is given in
      all cases by the expression N=(p2+/-q2)/J, where J is an integer giving the
      number of leaves on a single (e.g. stem) level. A biochemical origin of the
      algorithm is suggested.Copyright 1998 Academic Press Limited

PMID- 9782104
TI  - Information Theory, Scaling Laws and the Thermodynamics of Evolution.
AB  - Renormalization symmetry and the Legendre transformation are imposed on a
      parametized form of ergodic source uncertainty, a widely-applied model for
      "languages" ranging from the spoken word to genetic codes. Using the Shannon
      McMillan theorem to identify a duality between source uncertainty and free energy
      density, this procedure: (i) suggests that a punctuated "phase change" and
      resulting sudden fragmentation or coalescence should be the norm for "language"
      based phenomena, particularly the transfer of "genetic" information within
      reproducing populations; (ii) gives a power law for that phase change near
      transition; (iii) provides a "disorder" construct similar to an entropy which may
      trigger higher degrees of punctuation in social systems than is suggested from
      simple physical analogs; and (iv) gives "equations of state" relating ensemble
      averages which should be observable within coalesced systems. The general
      formalism is explicitly applied to problems of speciation, coevolution and group
      selection, and comparison made with the work of Eigen and his
      associates.Copyright 1998 Academic Press Limited

PMID- 9782105
TI  - Conceptual Capacity to Categorize and the Evolution of Altruism.
AB  - The conceptual capacity to categorize and consequently the ability to approve or
      reprove the one's and other's behavior allows the appearance of individuals with
      a new type of cooperative behavior that we have called "Assessor". The Assessor
      individual, if the partner behaves in a selfish way, reproves and penalizes this
      behavior changing his initial cooperation into defect. The reprobation permits
      that Assessor individuals, through simple observation, inhibit their altruistic
      behavior towards individuals whose selfish behavior has already been reproved,
      without having to interact with them. The evolutionary properties of Assessor
      behavior are analysed using the model of the iterated prisoner's dilemma where
      Assessor individuals compete with "always defect" individuals. The results are
      compared with those obtained, in the same circumstances, by other cooperative
      behaviors such as "always cooperate", "Tit-for-Tat" and "Observer-Tit-For-Tat".
      It is shown that in all situations Assessor is evolutionarily stronger than Tit
      for-Tat when both face ALL D. It is also advantageous with respect to Observer
      Tit-For-Tat in those situations that favor the evolution of reciprocal altruism
      "Tit-for Tat".Copyright 1998 Academic Press Limited

PMID- 9782116
TI  - Supraoptimal peptide-major histocompatibility complex causes a decrease in bc1-2
      levels and allows tumor necrosis factor alpha receptor II-mediated apoptosis of
      cytotoxic T lymphocytes.
AB  - Cytotoxic T lymphocytes (CTLs) are primary mediators of viral clearance, but high
      viral burden can result in deletion of antigen-specific CTLs. We previously
      reported a potential mechanism for this deletion: tumor necrosis factor (TNF)
      alpha-mediated apoptosis resulting from stimulation with supraoptimal peptide
      major histocompatibility complex. Here, we show that although death is mediated
      by TNF-alpha and its receptor (TNF-RII), surprisingly neither the antigen dose
      dependence of TNF-alpha production nor that of TNF-RII expression can account for
      the dose dependence of apoptosis. Rather, a previously unrecognized effect of
      supraoptimal antigen in markedly decreasing levels of the antiapoptotic protein
      Bc1-2 was discovered and is likely to account for the gain in susceptibility or
      competence to sustain the death signal through TNF-RII. This decrease requires a
      signal through the TCR, not just through TNF-RII. Although death mediated by TNF
      RII is not as widely studied as that mediated by TNF-RI, we show here that it is
      also dependent on proteolytic cleavage by caspases and triggered by a brief
      initial encounter with antigen. These results suggest that determinant density
      can regulate the immune response by altering the sensitivity of CTLs to the
      apoptotic effects of TNF-alpha by decreasing Bc1-2 levels.

PMID- 9782117
TI  - Identification of a late stage of small noncycling pTalpha- pre-T cells as
      immediate precursors of T cell receptor alpha/beta+ thymocytes.
AB  - During thymocyte development, progression from T cell receptor (TCR)beta to
      TCRalpha rearrangement is mediated by a CD3-associated pre-TCR composed of the
      TCRbeta chain paired with pre-TCRalpha (pTalpha). A major issue is how surface
      expression of the pre-TCR is regulated during normal thymocyte development to
      control transition through this checkpoint. Here, we show that developmental
      expression of pTalpha is time- and stage-specific, and is confined in vivo to a
      limited subset of large cycling human pre-T cells that coexpress low density CD3.
      This restricted expression pattern allowed the identification of a novel subset
      of small CD3(-) thymocytes lacking surface pTalpha, but expressing cytoplasmic
      TCRbeta, that represent late noncycling pre-T cells in which recombination
      activating gene reexpression and downregulation of T early alpha transcription
      are coincident events associated with cell cycle arrest, and immediately
      preceding TCRalpha gene expression. Importantly, thymocytes at this late pre-T
      cell stage are shown to be functional intermediates between large pTalpha+ pre-T
      cells and TCRalpha/beta+ thymocytes. The results support a developmental model in
      which pre-TCR-expressing pre-T cells are brought into cycle, rapidly downregulate
      surface pre-TCR, and finally become small resting pre-T cells, before the onset
      of TCRalpha gene expression.

PMID- 9782118
TI  - Fractalkine and CX3CR1 mediate a novel mechanism of leukocyte capture, firm
      adhesion, and activation under physiologic flow.
AB  - Leukocyte migration into sites of inflammation involves multiple molecular
      interactions between leukocytes and vascular endothelial cells, mediating
      sequential leukocyte capture, rolling, and firm adhesion. In this study, we
      tested the role of molecular interactions between fractalkine (FKN), a
      transmembrane mucin-chemokine hybrid molecule expressed on activated endothelium,
      and its receptor (CX3CR1) in leukocyte capture, firm adhesion, and activation
      under physiologic flow conditions. Immobilized FKN fusion proteins captured
      resting peripheral blood mononuclear cells at physiologic wall shear stresses and
      induced firm adhesion of resting monocytes, resting and interleukin (IL)-2
      activated CD8(+) T lymphocytes and IL-2-activated NK cells. FKN also induced cell
      shape change in firmly adherent monocytes and IL-2-activated lymphocytes. CX3CR1
      transfected K562 cells, but not control K562 cells, firmly adhered to FKN
      expressing ECV-304 cells (ECV-FKN) and tumor necrosis factor alpha-activated
      human umbilical vein endothelial cells. This firm adhesion was not inhibited by
      pertussis toxin, EDTA/EGTA, or antiintegrin antibodies, indicating that the firm
      adhesion was integrin independent. In summary, FKN mediated the rapid capture,
      integrin-independent firm adhesion, and activation of circulating leukocytes
      under flow. Thus, FKN and CX3CR1 mediate a novel pathway for leukocyte
      trafficking.

PMID- 9782120
TI  - Neutrophil-derived 5'-adenosine monophosphate promotes endothelial barrier
      function via CD73-mediated conversion to adenosine and endothelial A2B receptor
      activation.
AB  - During episodes of inflammation, polymorphonuclear leukocyte (PMN)
      transendothelial migration has the potential to disturb vascular barrier function
      and give rise to intravascular fluid extravasation and edema. However, little is
      known regarding innate mechanisms that dampen fluid loss during PMN-endothelial
      interactions. Using an in vitro endothelial paracellular permeability model, we
      observed a PMN-mediated decrease in endothelial paracellular permeability. A
      similar decrease was elicited by cell-free supernatants from activated PMN (FMLP
      10(-6) M), suggesting the presence of a PMN-derived soluble mediator(s).
      Biophysical and biochemical analysis of PMN supernatants revealed a role for PMN
      derived 5'-adenosine monophosphate (AMP) and its metabolite, adenosine, in
      modulation of endothelial paracellular permeability. Supernatants from activated
      PMN contained micromolar concentrations of bioactive 5'-AMP and adenosine.
      Furthermore, exposure of endothelial monolayers to authentic 5'-AMP and adenosine
      increased endothelial barrier function more than twofold in both human umbilical
      vein endothelial cells and human microvascular endothelial cells. 5'-AMP
      bioactivity required endothelial CD73-mediated conversion of 5'-AMP to adenosine
      via its 5'-ectonucleotidase activity. Decreased endothelial paracellular
      permeability occurred through adenosine A2B receptor activation and was
      accompanied by a parallel increase in intracellular cAMP. We conclude that
      activated PMN release soluble mediators, such as 5'-AMP and adenosine, that
      promote endothelial barrier function. During inflammation, this pathway may limit
      potentially deleterious increases in endothelial paracellular permeability and
      could serve as a basic mechanism of endothelial resealing during PMN
      transendothelial migration.

PMID- 9782119
TI  - Class switching in B cells lacking 3' immunoglobulin heavy chain enhancers.
AB  - The 40-kb region downstream of the most 3' immunoglobulin (Ig) heavy chain
      constant region gene (Calpha) contains a series of transcriptional enhancers
      speculated to play a role in Ig heavy chain class switch recombination (CSR). To
      elucidate the function of this putative CSR regulatory region, we generated mice
      with germline mutations in which one or the other of the two most 5' enhancers in
      this cluster (respectively referred to as HS3a and HS1,2) were replaced either
      with a pgk-neor cassette (referred to as HS3aN and HS1,2N mutations) or with a
      loxP sequence (referred to as HS3aDelta and HS1,2Delta, respectively). B cells
      homozygous for the HS3aN or HS1,2N mutations had severe defects in CSR to several
      isotypes. The phenotypic similarity of the two insertion mutations, both of which
      were cis-acting, suggested that inhibition might result from pgk-neor cassette
      gene insertion rather than enhancer deletion. Accordingly, CSR returned to normal
      in B cells homozygous for the HS3aDelta or HS1,2Delta mutations. In addition,
      induced expression of the specifically targeted pgk-neor genes was regulated
      similarly to that of germline CH genes. Our findings implicate a 3' CSR
      regulatory locus that appears remarkably similar in organization and function to
      the beta-globin gene 5' LCR and which we propose may regulate differential CSR
      via a promoter competition mechanism.

PMID- 9782121
TI  - Pancreatic beta cell-specific expression of thioredoxin, an antioxidative and
      antiapoptotic protein, prevents autoimmune and streptozotocin-induced diabetes.
AB  - The cytotoxicity of reactive oxygen intermediates (ROIs) has been implicated in
      the destruction of pancreatic beta cells in insulin-dependent diabetes mellitus
      (IDDM). Thioredoxin (TRX), a redox (reduction/oxidation)-active protein, has
      recently been shown to protect cells from oxidative stress and apoptosis. To
      elucidate the roles of oxidative stress in the development of autoimmune diabetes
      in vivo, we produced nonobese diabetic transgenic mice that overexpress TRX in
      their pancreatic beta cells. In these transgenic mice, the incidence of diabetes
      was markedly reduced, whereas the development of insulitis was not prevented.
      Moreover, induction of diabetes by streptozotocin, an ROI-generating agent, was
      also attenuated by TRX overexpression in beta cells. This is the first direct
      demonstration that an antioxidative and antiapoptotic protein protects beta cells
      in vivo against both autoimmune and drug-induced diabetes. Our results strongly
      suggest that oxidative stress plays an essential role in the destruction of beta
      cells by infiltrating inflammatory cells in IDDM.

PMID- 9782123
TI  - Assembly of productive T cell receptor delta variable region genes exhibits
      allelic inclusion.
AB  - The generation of a productive "in-frame" T cell receptor beta (TCR beta),
      immunoglobulin (Ig) heavy (H) or Ig light (L) chain variable region gene can
      result in the cessation of rearrangement of the alternate allele, a process
      referred to as allelic exclusion. This process ensures that most alphabeta T
      cells express a single TCR beta chain and most B cells express single IgH and IgL
      chains. Assembly of TCR alpha and TCR gamma chain variable region genes exhibit
      allelic inclusion and alphabeta and gammadelta T cells can express two TCR alpha
      or TCR gamma chains, respectively. However, it was not known whether assembly of
      TCR delta variable regions genes is regulated in the context of allelic
      exclusion. To address this issue, we have analyzed TCR delta rearrangements in a
      panel of mouse splenic gammadelta T cell hybridomas. We find that, similar to TCR
      alpha and gamma variable region genes, assembly of TCR delta variable region
      genes exhibits properties of allelic inclusion. These findings are discussed in
      the context of gammadelta T cell development and regulation of rearrangement of
      TCR delta genes.

PMID- 9782124
TI  - Antigen-dependent and -independent Ca2+ responses triggered in T cells by
      dendritic cells compared with B cells.
AB  - Dendritic cells (DCs) are much more potent antigen (Ag)-presenting cells than
      resting B cells for the activation of naive T cells. The mechanisms underlying
      this difference have been analyzed under conditions where ex vivo DCs or B cells
      presented known numbers of specific Ag-major histocompatibility complex (MHC)
      complexes to naive CD4(+) T cells from T cell antigen receptor (TCR) transgenic
      mice. Several hundred Ag-MHC complexes presented by B cells were necessary to
      elicit the formation of a few T-B conjugates with small contact zones, and the
      resulting individual T cell Ca2+ responses were all-or-none. In contrast, Ag
      specific T cell Ca2+ responses can be triggered by DCs bearing an average of 30
      Ag-MHC complexes per cell. Formation of T-DC conjugates is Ag-independent, but in
      the presence of the Ag, the surface of the contact zone increases and so does the
      amplitude of the T cell Ca2+ responses. These results suggest that Ag is better
      recognized by T cells on DCs essentially because T-DC adhesion precedes Ag
      recognition, whereas T-B adhesion requires Ag recognition. Surprisingly, we also
      recorded small Ca2+ responses in T cells interacting with unpulsed DCs. Using DCs
      purified from MHC class II knockout mice, we provide evidence that this signal is
      mostly due to MHC-TCR interactions. Such an Ag-independent, MHC-triggered calcium
      response could be a survival signal that DCs but not B cells are able to deliver
      to naive T cells.

PMID- 9782122
TI  - Antigens varying in affinity for the B cell receptor induce differential B
      lymphocyte responses.
AB  - The B cell receptor (BCR) triggers a variety of biological responses that differ
      depending upon the properties of the antigen. A panel of M13 phage-displayed
      peptide ligands with varying affinity for the 3-83 antibody was generated to
      explore the role of antigen-BCR affinity in cell activation studies using primary
      3-83 transgenic mouse B cells. Multiple parameters of activation were measured. T
      cell-independent B cell proliferation, antibody secretion, induction of germline
      immunoglobulin gamma1 transcripts, and B cell production of interleukin (IL) 2
      and interferon gamma responses were better correlated with antigen-BCR affinity
      than with receptor occupancy. In contrast, other responses, such as upregulation
      of major histocompatibility complex class II and B7.2 (CD86), secretion of IL-6,
      and B cell proliferation in the context of CD40 signaling were only weakly
      dependent on antigen affinity. Biochemical analysis revealed that at saturating
      ligand concentrations the ability of phage to stimulate some early signaling
      responses, such as Ca++ mobilization and tyrosine phosphorylation of syk or
      Igalpha, was highly affinity dependent, whereas the ability to stimulate Lyn
      phosphorylation was less so. These data suggest that the BCR is capable of
      differential signaling. The possibility that differential BCR signaling by
      antigen determines whether an antibody response will be T independent or
      dependent is discussed.

PMID- 9782125
TI  - Selective expression and functions of interleukin 18 receptor on T helper (Th)
      type 1 but not Th2 cells.
AB  - Interleukin (IL)-18 induces interferon (IFN)-gamma synthesis and synergizes with
      IL-12 in T helper type 1 (Th1) but not Th2 cell development. We report here that
      IL-18 receptor (IL-18R) is selectively expressed on murine Th1 but not Th2 cells.
      IL-18R mRNA was expressed constitutively and consistently in long-term cultured
      clones, as well as on newly polarized Th1 but not Th2 cells. IL-18 sustained the
      expression of IL-12Rbeta2 mRNA, indicating that IL-18R transmits signals that
      maintain Th1 development through the IL-12R complex. In turn, IL-12 upregulated
      IL-18R mRNA. Antibody against an IL-18R-derived peptide bound Th1 but not Th2
      clones. It also labeled polarized Th1 but not Th2 cells derived from naive
      ovalbumin-T cell antigen receptor-alphabeta transgenic mice (D011.10). Anti-IL
      18R antibody inhibited IL-18- induced IFN-gamma production by Th1 clones in
      vitro. In vivo, anti-IL-18R antibody reduced local inflammation and
      lipopolysaccharide-induced mortality in mice. This was accompanied by shifting
      the balance from Th1 to Th2 responses, manifest as decreased IFN-gamma and
      proinflammatory cytokine production and increased IL-4 and IL-5 synthesis.
      Therefore, these data provide a direct mechanism for the selective effect of IL
      18 on Th1 but not Th2 cells. They also show that the synergistic effect of IL-12
      and IL-18 on Th1 development may be due to the reciprocal upregulation of their
      receptors. Furthermore, IL-18R is a cell surface marker distinguishing Th1 from
      Th2 cells and may be a therapeutic target.

PMID- 9782126
TI  - Dendritic cells induce autoimmune diabetes and maintain disease via de novo
      formation of local lymphoid tissue.
AB  - Activation of autoreactive T cells can lead to autoimmune diseases such as
      insulin-dependent diabetes mellitus (IDDM). The initiation and maintenance of
      IDDM by dendritic cells (DC), the most potent professional antigen-presenting
      cells, were investigated in transgenic mice expressing the lymphocytic
      choriomeningitis virus glycoprotein (LCMV-GP) under the control of the rat
      insulin promoter (RIP-GP mice). We show that after adoptive transfer of DC
      constitutively expressing the immunodominant cytotoxic T lymphocyte (CTL) epitope
      of the LCMV-GP, RIP-GP mice developed autoimmune diabetes. Kinetic and functional
      studies of DC-activated CTL revealed that development of IDDM was dependent on
      dose and timing of antigenic stimulation. Strikingly, repeated CTL activation by
      DC led to severe destructive mononuclear infiltration of the pancreatic islets
      but also to de novo formation of islet-associated organized lymphoid structures
      in the pancreatic parenchyma. In addition, repetitive DC immunization induced
      IDDM with lymphoid neogenesis also in perforin-deficient RIP-GP mice,
      illustrating that CD8(+) T cell-dependent inflammatory mechanisms independent of
      perforin could induce IDDM. Thus, DC presenting self-antigens not only are potent
      inducers of autoreactive T cells, but also help to maintain a peripheral immune
      response locally; therefore, the induction of autoimmunity against previously
      ignored autoantigens represents a potential hazard, particularly in DC-based
      antitumor therapies.

PMID- 9782127
TI  - Generation of splenic follicular structure and B cell movement in tumor necrosis
      factor-deficient mice.
AB  - Secondary lymphoid tissue organogenesis requires tumor necrosis factor (TNF) and
      lymphotoxin alpha (LTalpha). The role of TNF in B cell positioning and formation
      of follicular structure was studied by comparing the location of newly produced
      naive recirculating and antigen-stimulated B cells in TNF-/- and TNF/LTalpha-/-
      mice. By creating radiation bone marrow chimeras from wild-type and TNF-/- mice,
      formation of normal splenic B cell follicles was shown to depend on TNF
      production by radiation-sensitive cells of hemopoietic origin. Reciprocal
      adoptive transfers of mature B cells between wild-type and knockout mice
      indicated that normal follicular tropism of recirculating naive B cells occurs
      independently of TNF derived from the recipient spleen. Moreover, soluble TNF
      receptor-IgG fusion protein administered in vivo failed to prevent B cell
      localization to the follicle or the germinal center reaction. Normal T zone
      tropism was observed when antigen-stimulated B cells were transferred into TNF-/-
      recipients, but not into TNF/LTalpha-/- recipients. This result appeared to
      account for the defect in isotype switching observed in intact TNF/LTalpha-/-
      mice because TNF/LTalpha-/- B cells, when stimulated in vitro, switched isotypes
      normally. Thus, TNF is necessary for creating the permissive environment for B
      cell movement and function, but is not itself responsible for these processes.

PMID- 9782128
TI  - Crystal structure of HLA-DR2 (DRA*0101, DRB1*1501) complexed with a peptide from
      human myelin basic protein.
AB  - Susceptibility to multiple sclerosis is associated with the human
      histocompatibility leukocyte antigen (HLA)-DR2 (DRB1*1501) haplotype. The
      structure of HLA-DR2 was determined with a bound peptide from human myelin basic
      protein (MBP) that is immunodominant for human MBP-specific T cells. Residues of
      MBP peptide that are important for T cell receptor recognition are prominent,
      solvent exposed residues in the crystal structure. A distinguishing feature of
      the HLA-DR2 peptide binding site is a large, primarily hydrophobic P4 pocket that
      accommodates a phenylalanine of the MBP peptide. The necessary space for this
      aromatic side chain is created by an alanine at the polymorphic DRbeta 71
      position. These features make the P4 pocket of HLA-DR2 distinct from DR molecules
      associated with other autoimmune diseases.

PMID- 9782129
TI  - CD1d-mediated recognition of an alpha-galactosylceramide by natural killer T
      cells is highly conserved through mammalian evolution.
AB  - Natural killer (NK) T cells are a lymphocyte subset with a distinct surface
      phenotype, an invariant T cell receptor (TCR), and reactivity to CD1. Here we
      show that mouse NK T cells can recognize human CD1d as well as mouse CD1, and
      human NK T cells also recognize both CD1 homologues. The unprecedented degree of
      conservation of this T cell recognition system suggests that it is fundamentally
      important. Mouse or human CD1 molecules can present the glycolipid alpha
      galactosylceramide (alpha-GalCer) to NK T cells from either species. Human T
      cells, preselected for invariant Valpha24 TCR expression, uniformly recognize
      alpha-GalCer presented by either human CD1d or mouse CD1. In addition, culture of
      human peripheral blood cells with alpha-GalCer led to the dramatic expansion of
      NK T cells with an invariant (Valpha24(+)) TCR and the release of large amounts
      of cytokines. Because invariant Valpha14(+) and Valpha24(+) NK T cells have been
      implicated both in the control of autoimmune disease and the response to tumors,
      our data suggest that alpha-GalCer could be a useful agent for modulating human
      immune responses by activation of the highly conserved NK T cell subset.

PMID- 9782130
TI  - CD1d-restricted recognition of synthetic glycolipid antigens by human natural
      killer T cells.
AB  - A conserved subset of mature circulating T cells in humans expresses an invariant
      Valpha24-JalphaQ T cell receptor (TCR)-alpha chain rearrangement and several
      natural killer (NK) locus-encoded C-type lectins. These human T cells appear to
      be precise homologues of the subset of NK1.1(+) TCR-alpha/beta+ T cells, often
      referred to as NK T cells, which was initially identified in mice. Here we show
      that human NK T cell clones are strongly and specifically activated by the same
      synthetic glycolipid antigens as have been shown recently to stimulate murine NK
      T cells. Responses of human NK T cells to these synthetic glycolipids, consisting
      of certain alpha-anomeric sugars conjugated to an acylated phytosphingosine base,
      required presentation by antigen-presenting cells expressing the major
      histocompatibility complex class I-like CD1d protein. Presentation of synthetic
      glycolipid antigens to human NK T cells required internalization of the
      glycolipids by the antigen-presenting cell and normal endosomal targeting of
      CD1d. Recognition of these compounds by human NK T cells triggered proliferation,
      cytokine release, and cytotoxic activity. These results demonstrate a striking
      parallel in the specificity of NK T cells in humans and mice, thus providing
      further insight into the potential mechanisms of immune recognition by NK T cells
      and the immunological function of this unique T cell subset.

PMID- 9782131
TI  - Neu differentiation factor (NDF), a dominant oncogene, causes apoptosis in vitro
      and in vivo.
AB  - Neu differentiation factor (NDF, also called neuregulin) is a potent inducer of
      epithelial cell proliferation and has been shown to induce mammary carcinomas in
      transgenic mice. Notwithstanding this proliferative effect, we have shown that a
      novel isoform of NDF can induce apoptosis when overexpressed. Here we report that
      this property also extends to other NDF isoforms and that the cytoplasmic portion
      of NDF is largely responsible for the apoptotic effect, whereas the proliferative
      activity is likely to depend upon the secreted version of NDF. In accordance with
      these contradictory properties, we find that tumors induced by NDF display
      extensive apoptosis in vivo. NDF is therefore an oncogene whose deregulation can
      induce transformation as well as apoptosis.

PMID- 9782134
TI  - Big dreams--clear vision.

PMID- 9782132
TI  - Rapid interferon gamma-dependent clearance of influenza A virus and protection
      from consolidating pneumonitis in nitric oxide synthase 2-deficient mice.
AB  - Viral infection often activates the interferon (IFN)-gamma-inducible gene, nitric
      oxide synthase 2 (NOS2). Expression of NOS2 can limit viral growth but may also
      suppress the immune system and damage tissue. This study assessed each of these
      effects in genetically deficient NOS2(-/-) mice after infection with influenza A,
      a virus against which IFN-gamma has no known activity. At inocula sufficient to
      cause consolidating pneumonitis and death in wild-type control mice, NOS2(-/-)
      hosts survived with little histopathologic evidence of pneumonitis. Moreover,
      they cleared influenza A virus from their lungs by an IFN-gamma-dependent
      mechanism that was not evident in wild-type mice. Even when the IFN-gamma
      mediated antiviral activity was blocked in NOS2(-/-) mice with anti-IFN-gamma
      mAb, such mice failed to succumb to disease. Further evidence that this
      protection was independent of viral load was provided by treating NOS2(+/+) mice
      with the NOS inhibitor, Nomega-methyl-L-arginine (L-NMA). L-NMA prevented
      mortality without affecting viral growth. Thus, host NOS2 seems to contribute
      more significantly to the development of influenza pneumonitis in mice than the
      cytopathic effects of viral replication. Although NOS2 mediates some antiviral
      effects of IFN-gamma, during influenza infection it can suppress another IFN
      gamma-dependent antiviral mechanism. This mechanism was observed only in the
      complete absence of NOS2 activity and appeared sufficient to control influenza A
      virus growth in the absence of changes in cytotoxic T lymphocyte activity.

PMID- 9782135
TI  - The early history of hysteroscopy.

PMID- 9782133
TI  - Uptake of Leishmania major amastigotes results in activation and interleukin 12
      release from murine skin-derived dendritic cells: implications for the initiation
      of anti-Leishmania immunity.
AB  - Epidermal Langerhans cells (LC) are immature dendritic cells (DC) located in
      close proximity to the site of inoculation of infectious Leishmania major
      metacyclic promastigotes by sand flies. Using LC-like DC expanded from C57BL/6
      fetal skin, we characterized interactions involving several developmental stages
      of Leishmania and DC. We confirmed that L. major amastigotes, but not
      promastigotes, efficiently entered LC-like DC. Parasite internalization was
      associated with activation manifested by upregulation of major histocompatibility
      complex (MHC) class I and II surface antigens, increased expression of
      costimulatory molecules (CD40, CD54, CD80, and CD86), and interleukin (IL)-12 p40
      release within 18 h. L. major-induced IL-12 p70 release by DC required interferon
      gamma and prolonged (72 h) incubation. In contrast, infection of inflammatory
      macrophages (Mphi) with amastigotes or promastigotes did not lead to significant
      changes in surface antigen expression or cytokine production. These results
      suggest that skin Mphi and DC are infected sequentially in cutaneous
      leishmaniasis and that they play distinct roles in the inflammatory and immune
      response initiated by L. major. Mphi capture organisms near the site of
      inoculation early in the course of infection after establishment of cellular
      immunity, and kill amastigotes but probably do not actively participate in T cell
      priming. In contrast, skin DC are induced to express increased amounts of MHC
      antigens and costimulatory molecules and to release cytokines (including IL-12
      p70) by exposure to L. major amastigotes that ultimately accumulate in lesional
      tissue, and thus very likely initiate protective T helper cell type 1 immunity.

PMID- 9782136
TI  - Energy systems for operative laparoscopy.

PMID- 9782137
TI  - Long-term economic evaluation of resectoscopic endometrial ablation versus
      hysterectomy for the treatment of menorrhagia.
AB  - STUDY OBJECTIVE: To assess long-term costs of resectoscopic endometrial ablation
      versus hysterectomy in women with menorrhagia. DESIGN: Controlled cohort study
      (Canadian Task Force classification II-2). SETTING: Multispeciality group
      practice. PATIENTS: Sixty-four women who underwent endometrial ablation during
      1992-1994 and 46 women who underwent hysterectomy during 1990-1992. To attain
      comparable controls, patients with uterine size exceeding 14 weeks or uterine
      weight greater than 300 g, ovarian pathology, endometriosis, or neoplasia were
      excluded. INTERVENTIONS: Endometrial ablation and hysterectomy, followed by
      economic evaluation. MEASUREMENTS AND MAIN RESULTS: Direct costs were
      hospitalization charges, professional fees, preoperative depot leuprolide, and
      gynecologic care during 3 years after primary surgery. Indirect costs were
      calculated based on known demographic data, recovery time, and lost productivity.
      Surgical outcomes, complications, repeat surgeries, menstrual outcomes, and
      overall patient satisfaction were assessed. Operating time (38 vs 107 min),
      hospital stay (0.7 vs 2.7 days), frequency of postoperative complications (6.3%
      vs 21.7%), and recuperation time (5 vs 32 days) were less with endometrial
      ablation than with hysterectomy. Mean follow-up was 48.5 months (range 36-68 mo),
      with rates of amenorrhea, hypomenorrhea, and eumenorrhea of 49%, 29%, and 8%,
      respectively. One patient was lost to follow-up. There were eight failures (12%):
      repeat endometrial ablations (2 women), abdominal hysterectomy (1), and
      laparoscopic-assisted hysterectomy (5). Most women (85%) remained satisfied with
      the operation. Total direct costs/case for endometrial ablation were $5434 versus
      $8417 for hysterectomy; respective indirect costs/case were $525 and $3360.
      Conclusion. Long-term direct and indirect costs of endometrial ablation were
      significantly less than those of hysterectomy ($5959 vs $11,777) for the
      treatment of menorrhagia.

PMID- 9782138
TI  - Does preoperative treatment with a gonadotropin-releasing hormone agonist improve
      the outcome of endometrial resection?
AB  - STUDY OBJECTIVE: To verify if more favorable long-term results of endometrial
      resection can be obtained with preoperative gonadotropin-releasing hormone (GnRH)
      agonist treatment. DESIGN: Multicenter, randomized, controlled trial (Canadian
      Task Force classification I). SETTING: Tertiary care academic department.
      PATIENTS: Sixty-three premenopausal women with established menorrhagia.
      INTERVENTION: Eight weeks of goserelin depot treatment before endometrial
      resection or immediate surgery in the early proliferative phase of the cycle.
      MEASUREMENTS AND MAIN RESULTS: Variations in menstrual patterns and bleeding
      scores as well as overall degree of satisfaction with treatment were determined 1
      year after endometrial resection. Mean +/- SD monthly pictorial blood loss
      assessment chart scores in the second 6-month follow-up period were 26.9 +/- 31.6
      in the goserelin group and 44.0 +/- 45.7 in the immediate surgery group (mean
      difference 17.1 points, 95% CI -3.0 to +37.2, p = 0.09, unpaired t test).
      Respective amenorrhea rates were 34% (11/32) and 20% (6/20, p = 0.26, Fisher's
      exact test, 95% CI of difference -8% to +37%). Overall satisfaction with
      treatment was 91% and 87%, respectively. CONCLUSION: Administration of a GnRH
      agonist before endometrial resection is advantageous for surgery, but has a
      limited effect in terms of postoperative bleeding pattern and appears not to
      offer clear-cut long-term clinical benefit.

PMID- 9782139
TI  - Ultrasonographic prediction of the efficacy of GnRH agonist therapy before
      laparoscopic myomectomy.
AB  - STUDY OBJECTIVE: To assess ultrasonographic prediction of the efficacy of
      administration of a gonadotropin-releasing hormone (GnRH) analog before
      laparoscopic myomectomy. DESIGN: Prospective, randomized study of women treated
      consecutively from September 1994 to July 1996 (Canadian Task Force
      classification I). SETTING: Endogyn Service, Private Endoscopic Associates,
      Naples, and Department of Gynecologic and Pediatric Sciences, Reggio Calabria
      University, Catanzaro, Italy. PATIENTS: Sixty-seven infertile women with
      symptomatic uterine myomata, mainly intramural, undergoing laparoscopic
      myomectomy. INTERVENTIONS: Patients were prospectively randomized in two groups.
      Group A received preoperative administration of two injections of a depot
      formulation of leuprolide acetate 28 days apart, and group B underwent direct
      surgery. In each group we studied the number, diameter, and echogenicity of
      larger fibroids; resistance index of uterine arteries and myoma vessels;
      operating time; and blood loss. MEASUREMENTS AND MAIN RESULTS: The two groups did
      not significantly differ in baseline ultrasonographic parameters. Both blood loss
      (p <0.01) and operating time (p <0.05) were significantly lower in group A.
      However, operating time was significantly longer when the main myoma was markedly
      hypoechoic. CONCLUSION: Our data confirm the therapeutic efficacy of
      administration of a GnRH analog before laparoscopic myomectomy in reducing blood
      loss and decreasing operating time in all cases except those with markedly
      hypoechoic fibroids.

PMID- 9782140
TI  - Uptake of the photosensitizer benzoporphyrin derivative in human endometrium
      after topical application in vivo.
AB  - STUDY OBJECTIVE: To determine both the time leading to maximum endometrial drug
      uptake and distribution of the photosensitizer benzoporphyrin derivative-monoacid
      ring A (BPD-MA) after intrauterine instillation (Canadian Task Force
      classification ). DESIGN: Assessment of histology specimens (Canadian Task Force
      classification I). SETTING: University-based facility. PATIENTS: Twenty-two women
      scheduled for hysterectomy. INTERVENTIONS: We instilled 1.5 ml of a 2 mg/ml of
      BPD-MA-Hyskon solution into the uterine cavity of 22 women before hysterectomy.
      The fluorescence induced was measured by fluorescence microscopy on frozen
      sections of uterine samples from 20 of 22 patients. Systemic uptake of BPD-MA was
      determined in plasma of six patients by spectrofluorometry. MEASUREMENTS AND MAIN
      RESULTS: The BPD-MA-induced fluorescence was maximum 1 hour after instillation,
      with significantly higher uptake in endometrial glands than in underlying stroma.
      Hormonal endometrial stimulation correlated with fluorescence intensity: atrophy
      < secretory phase < proliferative phase. Strongest fluorescence was seen in
      endometrial cancer. Drug uptake by endometrial glands was found at a depth of 2
      mm from the surface. Systemic uptake of BPD-MA was under the detection level of 2
      ng/ml after application. CONCLUSION: Fluorescence in human endometrial glands
      suggests that selective destruction of human endometrium with photodynamic
      therapy may be possible 1 hour after topical application of BPD-MA for benign and
      malignant lesions. No systemic drug uptake, side effects, or major technical
      difficulties were detected. Limited penetration of the drug and selective uptake
      by endometrial glands provided a high degree of safety for endometrial ablation.

PMID- 9782141
TI  - Comparison of ultrasonography and hysteroscopy in the diagnosis of intrauterine
      lesions in infertile women.
AB  - STUDY OBJECTIVE: To compare the effectiveness of transvaginal ultrasound versus
      hysteroscopy in the diagnosis of benign intrauterine lesions, with histology as
      the gold standard. DESIGN: Retrospective study (Canadian Task Force
      classification II-1). SETTING: Unit of Reproductive Medicine, Department of
      Obstetrics and Gynecology of Clinica Las Condes, Santiago, Chile. PATIENTS:
      Infertile women who had undergone complete fertility evaluation. INTERVENTION:
      Transvaginal ultrasound, hysteroscopy, and histologic evaluation of endometrial
      samples performed in all 126 women. MEASUREMENTS AND MAIN RESULTS: The most
      frequent condition was a normal cavity (59.5%), followed by endometrial polyps
      (34.9%) and fibromyomas (3.9%). Synechiae and bone metaplasia were extremely
      rare. Sensitivity of transvaginal ultrasound for the diagnosis of endometrial
      polyps was 95.6% compared with 89.9% for hysteroscopy (NS). Specificity was 97.4%
      with transvaginal ultrasound versus 93. 3% with hysteroscopy (NS). Positive and
      negative predictive values were similar for both methods. CONCLUSION:
      Transvaginal ultrasound is as effective as hysteroscopy in diagnosing benign
      intrauterine lesions. It could be the first clinical diagnostic test in the
      investigation of the uterine cavity.

PMID- 9782142
TI  - Staple pull-out strength in an animal model of Cooper's ligament.
AB  - STUDY OBJECTIVE: To understand the effect of staple number, orientation, and
      configuration on pull-out strength in an animal model of Cooper's ligament, and
      compare it with force to knot failure or suture breakage. DESIGN: Comparative
      study (Canadian Task Force classification I). SETTING: Ethicon Endo-Surgery
      Institute, Cincinnati, Ohio. SUBJECTS: Fibrous connective tissues from bovine
      ischia were the tissue model. INTERVENTION: Specimens were fixed in a cement
      plaster compound and mounted in a tensiometer. Endoscopic staples were used to
      hold a loop of 0-braided polyester suture to the tissue. MEASUREMENTS AND MAIN
      RESULTS: The suture loop was pulled perpendicularly away from tissue at a
      constant rate of 2.1 mm/second and peak force to staple pull-out was recorded.
      Two staple orientations and four staple configurations were studied. Tests were
      applied in a factorial arrangement. Ten-millimeter stitches of 0-braided
      polyester suture in the model were also tested. Maximum force to staple pull-out
      depended on staple number, orientation, and configuration. Peak force required to
      remove two staples was significantly higher than that to remove one. Spacing
      between two staples was less important. Pull-out strength was significantly
      higher when staples were placed parallel to tissue fibers. Stitches placed
      perpendicular to fibers failed at the knot or by suture breakage with a mean
      force approximately two times the peak force to remove two staples. CONCLUSION:
      Two staples placed 2 to 5 mm apart parallel to tissue fibers resulted in the
      greatest pull-out strength of studied configurations.

PMID- 9782143
TI  - Location of the transverse colon in relationship to the umbilicus: implications
      for laparoscopic techniques.
AB  - STUDY OBJECTIVE: To establish the location of the transverse colon in
      relationship to the umbilicus, and determine if it varies as a function of
      patient height or weight. DESIGN: Retrospective review of computed tomograms (CT)
      of the abdomen (Canadian Task Force classification II-2). SETTING: University
      hospital. PATIENTS: Sixty-seven women with normal abdominal anatomy.
      INTERVENTION: Review of abdominal CT scans. MEASUREMENTS AND MAIN RESULTS: The
      relative relationships of the transverse colon and umbilicus were compared with
      age, height, weight, and body mass index (BMI = kg/m2) using multiple regression
      analysis. Average location of the superior margin of the transverse colon was 4.6
      cm (95% CI 3.5-5.7 cm) above the umbilicus. In nine (13%) women it was below the
      umbilicus. The colon was below the umbilicus in 25% of nonobese women (BMI <25
      kg/m2). CONCLUSION: Because the transverse colon lies below the umbilicus in more
      than 10% of women, injury to it may be an uncommon yet unavoidable complication
      of laparoscopy.

PMID- 9782144
TI  - Changes in personality profile associated with laparoscopic surgery for chronic
      pelvic pain.
AB  - STUDY OBJECTIVE: To determine whether surgical treatment of chronic pelvic pain
      is associated with changes in personality profile. DESIGN: Prospective clinical
      trial (Canadian Task Force classification II-2). SETTING: University-affiliated
      tertiary referral center. PATIENTS: Sixteen women undergoing laparoscopic surgery
      for evaluation and treatment of chronic pelvic pain. INTERVENTION: Before and 3
      months after surgery all subjects completed the Minnesota multiphasic personality
      inventory-2 and the West Haven-Yale multidimensional pain inventory. MEASUREMENTS
      AND MAIN RESULTS: Laparoscopic surgery for chronic pelvic pain was associated
      with a postoperative decrease in pain severity score by 53% (p <0.001), increase
      in activity level score by 24% (p <0.001), decrease in hypochondriasis score by
      6% (p = 0.049), decrease in depression score by 12% (p = 0.007), and decrease in
      conversion hysteria score by 7% (p = 0.02). Improvements in pain severity and
      activity level were comparable in women with abnormal and normal preoperative
      scores of hypochondriasis, depression, and conversion hysteria. CONCLUSION:
      Improvement in chronic pelvic pain is associated with an improvement in
      personality profile. Abnormal versus normal preoperative scores for
      hypochondriasis, depression, or conversion hysteria scales are not predictive of
      change in pain or activity level after surgery.

PMID- 9782145
TI  - Outpatient diagnostic hysteroscopy.
AB  - STUDY OBJECTIVE: To evaluate the feasibility, validity, indications, and results
      of a large series of diagnostic hysteroscopies performed without anesthesia.
      DESIGN: Retrospective analysis of hysteroscopy charts performed between 1989 and
      1996 (Canadian Task Force classification II-2). SETTING: University-affiliated
      endoscopy unit. PATIENTS: Four thousand consecutive women referred for different
      indications. INTERVENTIONS: Diagnostic hysteroscopy was performed in 91% of
      patients without premedication or anesthetics. In some women premedication or
      general or local anesthesia was required to access the uterine cavity.
      MEASUREMENTS AND MAIN RESULTS: The success rate, validity indication,
      complication rate, and number of biopsies were critically evaluated and assessed
      in relation to increased experience of operators. In 91% of women we accessed the
      uterine cavity at the first attempt without premedication, whereas 207 (5. 1%)
      patients required local anesthesia and 99 (2.4%) premedication. Only 1.6%
      required general anesthesia. In 52% intrauterine pathology was diagnosed and in
      21% further surgical treatment was suggested. CONCLUSION: Hysteroscopy was
      feasible when performed in an outpatient setting without general or local
      anesthesia in more than 90% of women. The operator's experience seems a key
      factor both for accurate endometrial evaluation and to reduce failure and
      endometrial biopsy rates. The low frequency of further surgical treatment
      justifies performing the procedure in the office.

PMID- 9782146
TI  - Office microlaparoscopy under local anesthesia in the diagnosis and treatment of
      chronic pelvic pain.
AB  - STUDY OBJECTIVE: To evaluate the safety of diagnostic and operative
      microlaparoscopy performed in the office under local anesthesia in the diagnosis
      and treatment of chronic pelvic pain. DESIGN: Prospective study (Canadian Task
      Force classification II-2). SETTING: Office-based, free-standing private
      obstetrics and gynecology practice. PATIENTS: Twenty women with chronic pelvic
      pain. INTERVENTION: Diagnostic and operative microlaparoscopy performed under
      local anesthesia with conscious sedation. MEASUREMENTS AND MAIN RESULTS: All 20
      patients had diagnostic microlaparoscopy and 19 had conscious pain mapping. Nine
      of 14 patients with endometriosis underwent fulguration of lesions and 7 of 8
      with pelvic adhesions had lysis of adhesions. Four women with uterosacral
      ligament involvement had laparoscopic uterosacral nerve ablation. All patients
      tolerated office diagnostic and operative procedures without difficulty and had
      no complications. CONCLUSION: In selected women, several laparoscopic procedures
      traditionally done in a hospital or ambulatory surgery center under general
      anesthesia can be performed safely in the office laparoscopy suite under local
      anesthesia with conscious sedation.

PMID- 9782147
TI  - Laparoscopic radical hysterectomy with pelvic lymphadenectomy for early, invasive
      cervical carcinoma.
AB  - STUDY OBJECTIVE: To demonstrate the feasibility and evaluate the efficacy of
      laparoscopic radical hysterectomy with pelvic lymphadenectomy for early, invasive
      cervical cancer. DESIGN: Prospective study (Canadian Task Force classification II
      2). SETTING: University-affiliated hospital. PATIENTS: Eighteen women (age range
      29-70 yrs) with early, invasive cervical cancer. INTERVENTION: Laparoscopic
      radical hysterectomy with pelvic lymphadenectomy. MEASUREMENTS AND MAIN RESULTS:
      Diagnoses were squamous cell carcinoma in15 patients and adenocarcinoma of the
      cervix in 3; these were graded microcarcinoma in 6 and stage Ib (<4 cm) in 12.
      Mean operating time was approximately 363 +/- 65 minutes (range 240-475 min).
      Blood loss averaged 619 +/- 297 ml (range 250-1000 ml). The average number of
      pelvic lymph nodes obtained was 22.0 +/- 8.5 (range 14-40). Specimen weight
      averaged 117 +/- 67 g (range 60-340 g). Surgical margins were clear in all
      patients. No procedure was converted to laparotomy. There were no major
      intraoperative complications involving injury to main blood vessels, nerves,
      bowel, bladder, or ureters. CONCLUSION: In our experience, laparoscopic radical
      hysterectomy with pelvic lymphadenectomy is acceptable in accordance with the
      standards of gynecologic oncology. Despite the longer operating time than
      traditional abdominal radical hysterectomy, all patients recovered as quickly as
      they would after laparoscopic-assisted vaginal hysterectomy. We believe that this
      procedure could be an alternative to abdominal radical hysterectomy for selected
      women, especially those who have stage Ib1 cervical cancer.

PMID- 9782149
TI  - Laparoscopic removal of a bladder leiomyoma.
AB  - Bladder leiomyoma is a rare tumor that is generally removed by transabdominal,
      vaginal, and transurethral approaches. We successfully removed a large,
      transmural, extravesical bladder leiomyoma by laparoscopy.

PMID- 9782148
TI  - Initial experience with a physiologic morcellating resectoscope.
AB  - A new physiologic morcellating resectoscope allows operative hysteroscopy to be
      performed with a physiologic distention medium, thus reducing the risk of
      dilutional hyponatremia and cerebral edema secondary to excessive absorption of
      nonphysiologic fluid. To study this new technology, we gathered in vitro data
      with the SL resectoscope with dual-function electrode (FemRx, Sunnyvale, CA).
      Coupled to a standard monopolar electrosurgery unit and operating in normal
      saline or Ringer's lactate solution, extirpated uteri showed equivalent depth of
      tissue necrosis with this new physiologic morcellating resectoscope as with a
      conventional monopolar resectoscope used in an electrically nonconductive fluid.

PMID- 9782150
TI  - Prevention and management of omental herniation after laparoscopy.
AB  - Omental herniation through laparoscopic cannula sites is an uncommon but serious
      complication of laparoscopy. Its frequency will probably increase as more and
      different types of endoscopic surgery are performed. Omental herniation occurred
      in two women and was corrected under local anesthesia.

PMID- 9782151
TI  - Successful management of chylous ascites after laparoscopic presacral neurectomy.
AB  - Laparoscopic presacral neurectomy is a safe, effective, and well-established
      surgical procedure to relieve intractable dysmenorrhea and chronic pelvic pain.
      In one woman, substantial lymphatic leakage occurred due to damaged lymphatic
      vessels. Adequate exposure and coagulation of the presacral lymphatic zone
      through the laparoscope resolved the problem, and a substantial amount of chylous
      ascites was removed. The patient fully recovered after the intervention.

PMID- 9782152
TI  - Laparoscopic removal of a 5-cm subserous pedunculated myoma with small
      instruments.
AB  - A mobile, subserous, pedunculated myoma was located on the anterior surface of
      the uterus in a 45-year-old woman. Bipolar coagulation was performed on the
      pedicle, and the myoma was dissected with an electrical morcellator and removed
      through the umbilicus. This technique required placement of one 5- to 12-mm
      cannula in the umbilicus and two 2-mm miniports at the pubic hairline. This
      technique is easy to perform, and the patient benefits from minimal postoperative
      pain and excellent cosmetic results.

PMID- 9782153
TI  - Another trigger for the heartbeat.

PMID- 9782154
TI  - Voltage-controlled Ca2+ release in normal and ryanodine receptor type 3 (RyR3)
      deficient mouse myotubes.
AB  - 1. Primary cultured myotubes were derived from satellite cells of the diaphragm
      obtained from both normal mice (RyR3+/+) and mice with a targeted mutation
      eliminating expression of the type 3 isoform of the ryanodine receptor (RyR3-/-).
      Using the whole-cell patch clamp technique, L-type Ca2+ currents were measured
      during step depolarizations. Simultaneously, intracellular Ca2+ transients were
      recorded with the fluorescent indicator dye fura-2. 2. After correction for non
      instantaneous binding of Ca2+ to the indicator dye and taking into account the
      dynamics of Ca2+ binding to intracellular constituents, an estimate of the time
      course of the Ca2+ release rate from the sarcoplasmic reticulum (SR) was
      obtained. 3. The calculated SR Ca2+ release flux exhibited a marked peak within
      less than 12 ms after the onset of the voltage-clamp depolarization and fell
      rapidly thereafter to a five times lower, almost steady level. It declined
      rapidly after termination of the depolarization. 4. Signals in normal and RyR3
      deficient myotubes showed no significant difference in the activation of Ca2+
      conductance and in amplitude, time course and voltage dependence of the Ca2+
      efflux from the SR. 5. In conclusion, the characteristics of voltage-controlled
      Ca2+ release reported here are similar to those of mature mammalian muscle
      fibres. In contrast to differences observed in the contractile properties of RyR3
      deficient muscle fibres, a contribution of RyR3 to excitation-contraction
      coupling could not be detected in myotubes.

PMID- 9782155
TI  - Fatty acids stimulate cholecystokinin secretion via an acyl chain length
      specific, Ca2+-dependent mechanism in the enteroendocrine cell line STC-1.
AB  - 1. The present study has investigated whether fatty acids directly influence
      peptide release from enteroendocrine cells using STC-1, a mouse intestinal
      endocrine tumour cell line, previously shown to release cholecystokinin (CCK) in
      response to other physiological stimuli. 2. Fatty acids elicited a chain length-
      and dose-dependent stimulation of CCK secretion. Dodecanoic acid (C12) was most
      effective, producing up to a 5-fold increase in CCK secretion. Fatty acids with
      less than ten carbon atoms did not increase secretion. The chain length
      dependence of these effects mimics closely fatty acid-induced CCK secretion
      previously observed in humans in vivo. 3. Esterification of C12 abolished CCK
      secretion, indicating a critical role for a free carboxyl group in eliciting
      secretion. In contrast, modification of the methyl terminus had no effect on C12
      induced secretion. The non-metabolizable C12 analogue 2-bromododecanoic acid was
      equally effective. 4. C12 elicited a marked increase in intracellular calcium
      levels (200-300 nM) in STC-1 cells which was abolished by the L-type Ca2+ channel
      antagonist nicardipine. In contrast, C8 produced a smaller and more transient
      Ca2+ response. C12-induced CCK secretion was also blocked by nicardipine. 5.
      These data suggest that fatty acids can interact directly with enteroendocrine
      cells to stimulate CCK secretion via increases in intracellular calcium mediated
      primarily by L-type Ca2+ channels.

PMID- 9782156
TI  - Single-channel currents of a peptide-gated sodium channel expressed in Xenopus
      oocytes.
AB  - 1. Single-channel recordings were made from outside-out membrane patches of
      Xenopus oocytes injected with the cDNA clone FaNaCh, which encodes a peptide
      gated Na+ channel from Helix aspersa. 2. The natural peptides FMRFamide and
      FLRFamide only activated unitary currents in oocytes injected with FaNaCh; the
      EC50 values were 1.8 and 11.7 microM, respectively. 3. The slope conductance of
      the channel was 9.2 pS for both peptides. 4. With FMRFamide, the open probability
      (Po) of the channel was 0.06 at 0.3 microM and 0.76 at 30 microM, whereas for
      FLRFamide the open probability increased from 0.04 at 1.8 microM to 0.49 at 50
      microM. The Hill coefficient was greater than 1 for both peptides. 5. High
      concentrations of each peptide evoked very fast flickering between open and
      closed states which led to decreased unitary current amplitude. 6. At low doses,
      brief single openings and bursts of longer openings occurred. With higher doses,
      the occurrence of the brief openings declined and the number of longer openings
      increased; the duration of the longer openings was shorter with FLRFamide than
      with FMRFamide. 7. For each peptide, frequency distribution histograms of open
      events were best fitted by the sum of two exponential components, suggesting the
      existence of two open states of the channel. Closed events were fitted by the sum
      of three components, suggesting the existence of three closed states. 8. The data
      were analysed according to a five-state model in which the brief openings
      correspond to a single liganded open form of the channel and the longer openings
      to a doubly liganded open form. According to this interpretation, the greater
      whole-cell response observed with FMRFamide than with FLRFamide results mostly
      from a slower closing rate constant for the longer (doubly liganded) channel
      openings.

PMID- 9782157
TI  - GABAA and GABAC receptors in adult porcine cones: evidence from a photoreceptor
      glia co-culture model.
AB  - 1. Edge contrast enhancement is an integrated visual function based on the
      complex centre-surround organization of the cone photoreceptor light response.
      While centre responses result from direct light activation, surround responses
      are thought to result from lateral inhibition mediated by horizontal cells. This
      feedback signal has been attributed to GABAA receptors which have been found in
      lower vertebrate cones. 2. In order to study the GABA response of adult mammalian
      photoreceptors, we designed a culture system consisting of isolated
      photoreceptors seeded on a layer of retinal glial cells. Mature rods and cones
      required the presence of Muller glial cells to survive and develop neurites; they
      degenerated in the absence of glial cells. 3. Cone photoreceptors generated large
      GABA responses whereas rod photoreceptors did not respond to GABA applications.
      4. Cone GABA responses consisted of two distinct components, one suppressed by
      the GABAA receptor blockers bicuculline and SR95531, and the second by the GABAC
      receptor antagonists TPMPA and imidazole-4-acetic acid (I4AA). Pentobarbital
      greatly increased the GABAA receptor component whereas it did not affect, or even
      reduced, the GABAC receptor component. During long GABA applications, GABAA
      receptor currents desensitized by 78%, contrasting with the sustained GABAC
      response. 5. Expression of GABAC receptors in cone photoreceptors was confirmed
      by anti-rho-subunit immunolabelling of porcine retinal sections. 6. These results
      indicate that both GABAA and GABAC receptors may participate in the feedback
      synapse from horizontal cells to cone photoreceptors in the mammalian retina.

PMID- 9782158
TI  - Effects of caffeine and adenine nucleotides on Ca2+ release by the sarcoplasmic
      reticulum in saponin-permeabilized frog skeletal muscle fibres.
AB  - 1. The effect of caffeine and adenine nucleotides on the sarcoplasmic reticulum
      (SR) Ca2+ release mechanism was investigated in permeabilized frog skeletal
      muscle fibres. Caffeine was rapidly applied and the resulting release of Ca2+
      from the SR detected using fura-2 fluorescence. Decreasing the [ATP] from 5 to
      0.1 mM reduced the caffeine-induced Ca2+ transient by 89 +/- 1.4% (mean +/-
      s.e.m., n = 16), while SR Ca2+ uptake was unaffected. 2. The dependence of
      caffeine-induced Ca2+ release on cytosolic [ATP] was used to study the relative
      ability of other structurally related compounds to substitute for, or compete
      with, ATP at the adenine nucleotide binding site. It was found that AMP, ADP and
      the non-hydrolysable analogue adenylyl imidodiphosphate (AMP-PNP) partially
      substituted for ATP, although none was as potent in facilitating the Ca2+
      releasing action of caffeine. 3. Adenosine reversibly inhibited caffeine-induced
      Ca2+ release, without affecting SR Ca2+ uptake. Five millimolar adenosine
      markedly reduced the amplitude of the caffeine-induced Ca2+ transient by 64 +/-
      4% (mean +/- s.e.m., n = 11). The degree of inhibition was dependent upon the
      cytosolic [ATP], suggesting that adenosine may act as a competitive antagonist at
      the adenine nucleotide binding site. 4. These data show that (i) the sensitivity
      of the in situ SR Ca2+ channel to caffeine activation is strongly dependent upon
      the cytosolic [ATP], (ii) the number of phosphates attached to the 5' carbon of
      the ribose ring influences the efficacy of the ligand, and (iii) removal of a
      single phosphate group transforms AMP from a partial agonist, to adenosine, which
      acts as a competitive antagonist under these conditions.

PMID- 9782159
TI  - Properties and functions of calcium-activated K+ channels in small neurones of
      rat dorsal root ganglion studied in a thin slice preparation.
AB  - 1. Properties, kinetics and functions of large conductance calcium-activated K+
      channels (BKCa) were investigated by the patch-clamp technique in small neurones
      (Adelta- and C-type) of a dorsal root ganglion (DRG) thin slice preparation
      without enzymatic treatment. 2. Unitary conductance of BKCa channels measured in
      symmetrical high K+ solutions (155 mM) was 200 pS for inward currents, and chord
      conductance in control solution was 72 pS. Potentials of half-maximum activation
      (V ) of the channels were linearly shifted by 43 mV per log10 [Ca2+]i unit (pCa)
      in the range of -28 mV (pCa 4) to +100 mV (pCa 7). Open probabilities increased e
      times per 15-32 mV depolarization of potential. 3. In mean open probability, fast
      changes with time were mainly observed at pCa > 6 and at potentials > +20 mV,
      without obvious changes in the experimental conditions. 4. BKCa channels were
      half-maximally blocked by 0.4 mM TEA, measured by apparent amplitude reductions.
      They were completely blocked by 100 nM charybdotoxin and 50 nM iberiotoxin by
      reduction of open probability. 5. Two subtypes of small DRG neurones could be
      distinguished by the presence (type I) or absence (type II) of BKCa channels. In
      addition, less than 10 % of small neurones showed fast (approximately 135 V s-1)
      and short ( approximately 0.8 ms) action potentials (AP). 6. The main functions
      of BKCa channels were found to be shortening of AP duration, increasing of the
      speed of repolarization and contribution to the fast after-hyperpolarization. As
      a consequence, BKCa channels may reduce the amount of calcium entering a neurone
      during an AP. 7. BKCa channel currents suppressed a subsequent AP and prolonged
      the refractory period, which might lead to a reduced repetitive activity. We
      suggest that the BKCa current is a possible mechanism of the reported conduction
      failure during repetitive stimulation in DRG neurones.

PMID- 9782160
TI  - Layer-specific NO dependence of long-term potentiation and biased NO release in
      layer V in the rat auditory cortex.
AB  - 1. We investigated the role of nitric oxide (NO) in the induction of long-term
      potentiation (LTP) in slices prepared from the rat auditory cortex. 2. Tetanic
      stimulation of layer IV elicited LTP of field potentials in layer II-III (LTPII
      III) and in layer V (LTPV). The magnitude of LTPII-III measured at 30 min after
      tetanic stimulation was 171 +/- 9% (n = 15, mean +/- s.e.m.) of the control
      measured before tetanic stimulation, while that of LTPV was 138 +/- 3% (n = 17).
      3. NO synthase (NOS) inhibitors had no apparent effect on LTPII-III, but LTPV was
      significantly suppressed (P < 0.001). This suppression of LTPV was significantly
      antagonized by a NO donor (P < 0.001) or a cGMP analogue (P < 0.001). 4. Small
      non-pyramidal neurones in the auditory cortex were stained with an anti-neuronal
      NOS antibody. More neurones were stained with the antibody in the deeper cortical
      layers. 5. We measured neocortical NO release with electrochemical NO probes.
      Layer IV stimulation elicited significantly more NO release in layer V than in
      layer II-III (P < 0.001). The amplitude of the increase in NO concentration
      elicited by stimulation at 20 Hz for 5 s was 380 +/- 14 pM (n = 55) in layer V
      and 55 +/- 8 pM (n = 5) in layer II-III. 6. NO release in layer V was partially
      but significantly suppressed by non-NMDA (P < 0.002) or NMDA (P < 0.002) receptor
      antagonists. Simultaneous application of the antagonists of the two types blocked
      NO release almost completely. 7. These results clearly indicate the NO dependence
      of the induction of LTPV, and the greater NO release in the deeper layer of the
      rat auditory cortex.

PMID- 9782161
TI  - Differential modulation of the phases of a Ca2+ spike by the store Ca2+-ATPase in
      human umbilical vein endothelial cells.
AB  - 1. Histamine-stimulated cytosolic free Ca2+ ([Ca2+]i) oscillations in human
      umbilical vein endothelial cells (HUVECs) comprise repetitive spikes generated by
      pulsatile release from stores. We have investigated the roles of the store Ca2+
      ATPases in regulating both the upstroke and downstroke of a Ca2+ spike. 2. The
      sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) inhibitor cyclopiazonic acid
      (CPA) dramatically affected oscillations whereas inhibition of the plasma
      membrane Ca2+-ATPase (PMCA) with La3+ had little effect. This and other evidence
      suggested that the downstroke of a spike is predominantly mediated by SERCA. 3.
      Artificial [Ca2+]i spiking generated by repetitive pulsatile application of 0.3
      microM histamine in Ca2+-free medium did not cause net loss of Ca2+ from the cell
      whereas repetitive pulsatile application of 1 and 10 microM histamine did, with
      the higher concentration being more effective. We conclude that there is an
      inverse relationship between stimulus intensity and relative SERCA activity. 4.
      For a Ca2+ transient, the initiation of release was suppressed by SERCA during
      either the lag phase or the interspike period (ISP) since: (i) the ISP was
      shortened by low CPA concentrations, (ii) higher concentrations of CPA stimulated
      an explosive Ca2+ release when applied during the ISP but not when applied in the
      absence of agonist, and (iii) CPA synchronized the initial Ca2+ response to a low
      histamine dose (even recruiting silent, histamine-unresponsive cells). 5. Two
      aspects of the regenerative upstroke of a spike were differently affected by
      SERCA inhibition: Ca2+ wave velocity was entirely unaffected by CPA whereas the
      local rate of rise was increased. 6. The [Ca2+]i at which a Ca2+ spike terminated
      depended on SERCA since CPA dose dependently enhanced the peak [Ca2+]i. 7. We
      conclude that SERCA plays a powerful and dynamic role in regulating [Ca2+]i
      oscillations in HUVECs. SERCA differentially modulates the phases of Ca2+ release
      in addition to bringing about the falling phase of a Ca2+ spike.

PMID- 9782163
TI  - Cholinergic activation and tonic excitation induce persistent gamma oscillations
      in mouse somatosensory cortex in vitro.
AB  - 1. Concomitant application of the cholinergic agonist carbachol and nanomolar
      doses of kainate can elicit persistent gamma frequency oscillations in all layers
      of the mouse somatosensory cortex in vitro. Receptor pharmacology with bath
      applied antagonists indicated that oscillatory network activity depended
      crucially on the participation of cholinergic muscarinic, (S)-alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate and GABAA receptors. 2.
      The timing of action potentials and the occurrence of excitatory as well as
      inhibitory postsynaptic events was highly correlated with the phasic change of
      extracellularly recorded population activity. Firing probability was lowest
      during the peak negativity of IPSPs and gradually increased during their ensuing
      decay. In conjunction with the effect of a barbiturate to decrease the frequency
      of gamma oscillations, this suggests a crucial role of IPSPs in phasing the
      suprathreshold activity of principal neurons. 3. At nearby (< 1 mm) sites
      contained within any given cortical layer, oscillatory extra- and intracellular
      activity was highly synchronous with no apparent phase lag. However, interlaminar
      mapping experiments demonstrated a phase reversal of both extra- and
      intracellularly recorded activity near the lower border of thalamo-recipient
      layer 4, thus corroborating findings that have been obtained in vivo. 4. In
      conclusion, a modest increase of tonic excitatory drive in conjunction with the
      activation of cholinergic muscarinic receptors can elicit persistent gamma
      frequency network oscillations in the rodent somatosensory cortex. These findings
      (re)emphasize the role of the cholinergic ascending system in the cortical
      processing of sensory information.

PMID- 9782162
TI  - An intercellular regenerative calcium wave in porcine coronary artery endothelial
      cells in primary culture.
AB  - 1. A regenerative calcium wave is an increase in cytosolic free calcium
      concentration ([Ca2+]i) which extends beyond the stimulated cells without
      decrement of amplitude, kinetics of [Ca2+]i increase and speed of propagation. 2.
      The aim of the present study was to test the hypothesis that such a wave could be
      evoked by bradykinin stimulation and by scraping cultured endothelial cells from
      porcine coronary arteries. 3. Calcium imaging was performed using the calcium
      sensitive dye fura-2. A wound or a delivery of bradykinin to two to three cells
      on growing clusters of approximately 300 cells caused an increase in [Ca2+]i
      which was propagated throughout the cluster in a regenerative manner over
      distances up to 400 micrometer. This wave spread through gap junctions since it
      was inhibited by the cell uncoupler palmitoleic acid. 4. The same experiments
      performed in confluent cultures caused a rise in [Ca2+]i which failed to
      propagate in a regenerative way. The wave propagation probably failed because the
      confluent cells were less dye coupled than the growing cells. This was confirmed
      by immunohistology which detected a dramatic decrease in the number of connexin
      40 gap junctions in the confluent cultures. 5. The regenerative propagation of
      the wave was blocked by inhibitors of calcium-induced calcium release (CICR) and
      phospholipase C (PLC), and by suppression of extracellular calcium, but not by
      clamping the membrane potential with high-potassium solution. 6. We conclude that
      regenerative intercellular calcium waves exist in cultured islets but not in
      confluent cultures of endothelial cells. An increase in [Ca2+]i is not sufficient
      to trigger a regenerative propagation. The PLC pathway, CICR and extracellular
      calcium are all necessary for a fully regenerated propagation.

PMID- 9782164
TI  - The development of conduction block in single human axons following a focal nerve
      injury.
AB  - 1. Using microneurography with a conventional monopolar electrode, the action
      potentials of ten myelinated axons in the peripheral nerves of human subjects
      were followed while they developed conduction block. 2. The action potentials had
      initially (n = 6) or developed (n = 4) a positive double-peaked morphology. The
      time interval between the two positive peaks represents the conduction time
      across the impaled internode. 3. When the interpeak interval was < 500 micros,
      conduction across the site of impalement was secure, even if the conduction time
      was markedly prolonged. When the interval was > 600 microseconds, intermittent
      conduction failure occurred. For all units the longest interpeak interval
      recorded just prior to complete conduction failure was, on average, 1.12 ms
      (range, 0.8-1.4 ms). 4. For five axons, there was evidence that natural activity
      triggered the conduction failure. 5. Impalement of the nerve fibre by the
      microelectrode impairs the ability of the axon to conduct impulses across the
      site of injury, but impulse transmission can be secure even when the conduction
      time across individual internodes is prolonged to 500 microseconds. These
      findings are therefore relevant to the conduction deficits that occur in focal
      injuries of human axons.

PMID- 9782165
TI  - Transmitter release modulation in nerve terminals of rat neocortical pyramidal
      cells by intracellular calcium buffers.
AB  - 1. Dual whole-cell voltage recordings were made from synaptically connected layer
      5 (L5) pyramidal neurones in slices of the young (P14-P16) rat neocortex. The
      Ca2+ buffers BAPTA or EGTA were loaded into the presynaptic neurone via the
      pipette recording from the presynaptic neurone to examine their effect on the
      mean and the coefficient of variation (c.v.) of single fibre EPSP amplitudes,
      referred to as unitary EPSPs. 2. The fast Ca2+ buffer BAPTA reduced unitary EPSP
      amplitudes in a concentration dependent way. With 0.1 mM BAPTA in the pipette,
      the mean EPSP amplitude was reduced by 14 +/- 2.8% (mean +/- s.e.m., n = 7)
      compared with control pipette solution, whereas with 1.5 mM BAPTA, the mean EPSP
      amplitude was reduced by 72 +/- 1.5% (n = 5). The concentration of BAPTA that
      reduced mean EPSP amplitudes to one-half of control was close to 0.7 mM. 3.
      Saturation of BAPTA during evoked release was tested by comparing the effect of
      loading the presynaptic neurone with 0.1 mM BAPTA at 2 and 1 mM [Ca2+]o. Reducing
      [Ca2+]o from 2 to 1 mM, thereby reducing Ca2+ influx into the terminals,
      decreased the mean EPSP amplitude by 60 +/- 2.2% with control pipette solution
      and by 62 +/- 1.9% after loading with 0.1 mM BAPTA (n = 7). 4. The slow Ca2+
      buffer EGTA at 1 mM reduced mean EPSP amplitudes by 15 +/- 2.5% (n = 5). With 10
      mM EGTA mean EPSP amplitudes were reduced by 56 +/- 2.3 % (n = 4). 5. With both
      Ca2+ buffers, the reduction in mean EPSP amplitudes was associated with an
      increase in the c.v. of peak EPSP amplitudes, consistent with a reduction of the
      transmitter release probability as the major mechanism underlying the reduction
      of the EPSP amplitude. 6. The results suggest that in nerve terminals of thick
      tufted L5 pyramidal cells the endogenous mobile Ca2+ buffer is equivalent to less
      than 0.1 mM BAPTA and that at many release sites of pyramidal cell terminals the
      Ca2+ channel domains overlap, a situation comparable with that at large calyx
      type terminals in the brainstem.

PMID- 9782166
TI  - Facilitation of presynaptic calcium currents in the rat brainstem.
AB  - 1. To study use-dependent changes in the presynaptic Ca2+ influx and their
      contribution to transmitter release, we made simultaneous voltage clamp
      recordings from presynaptic terminals (the calyces of Held) and postsynaptic
      cells (the principal cells of the medial nucleus of the trapezoid body) in slices
      of the rat auditory brainstem. 2. Following a short (2 ms) prepulse to 0 mV,
      calcium channels opened faster during steps to negative test potentials. During
      trains of action potential waveforms the Ca2+ influx per action potential
      increased. At the same time, however, the amplitude of the EPSCs decreased. 3.
      The facilitation of the calcium currents appeared to depend on a build-up of
      intracellular Ca2+, since its magnitude was proportional to the Ca2+ influx and
      it was reduced in the presence of 10 mM BAPTA. 4. Facilitation of the presynaptic
      calcium currents may contribute to short-term facilitation of transmitter
      release, observed when quantal output is low. Alternatively, it may counteract
      processes that contribute to synaptic depression.

PMID- 9782167
TI  - Two types of parasympathetic preganglionic neurones in the superior salivatory
      nucleus characterized electrophysiologically in slice preparations of neonatal
      rats.
AB  - 1. The electrophysiological properties of parasympathetic preganglionic neurones
      in the superior salivatory nucleus were studied in thin- and thick-slice
      preparations of rats aged 1 and 2 weeks using the whole-cell patch-clamp
      technique. 2. The superior salivatory neurones were identified by a retrograde
      tracing method with dextran-tetramethylrhodamine-lysine. The injection of the
      tracer into the chorda-lingual nerve labelled the neurones innervating the
      submandibular ganglia and those innervating the intra-lingual ganglia, while the
      injection into the tip of the tongue labelled the latter group of neurones. 3.
      Firing characteristics were investigated mainly in the neurones of 6-8 days
      postnatal rats. In response to an injection of long depolarizing current pulses
      at hyperpolarized membrane potentials (< -80 mV) under a current clamp, the
      neurones labelled from the nerve displayed a train of action potentials with
      either a long silent period preceding the first spike (late spiking pattern) or a
      long silent period interposed between the first and second spikes (interrupted
      spiking pattern). The neurones labelled from the tongue invariably displayed the
      interrupted spiking pattern. 4. Under a voltage clamp, among the neurones from 6
      8 days postnatal rats, those labelled from the nerve expressed either a fast or a
      slow transient outward current (A-current), while those labelled from the tongue
      invariably showed a slow transient outward current. Both the fast and slow A
      currents were largely depressed by 1 mM 4-aminopyridine. 5. Similar fast and slow
      A-currents were observed in the neurones of rats aged 14-15 days. Both the time
      to peak and decay time constant of these A-currents were accelerated, suggesting
      a developmental trend of maturation in the activation and inactivation kinetics
      between 6 and 15 days postnatal. 6. Based on the differences in the firing
      pattern and outward current, the superior salivatory neurones can be separated
      into two distinct types. We discuss the functional aspects of these two types of
      neurones with reference to their target organs.

PMID- 9782168
TI  - Role of myosin heavy chain composition in kinetics of force development and
      relaxation in rat myocardium.
AB  - 1. The effects of ventricular myosin heavy chain (MHC) composition on the
      kinetics of activation and relaxation were examined in both chemically skinned
      and intact myocardial preparations from adult rats. Thyroid deficiency was
      induced to alter ventricular MHC isoform expression from approximately 80% alpha
      MHC/20% beta-MHC in euthyroid rats to 100% beta-MHC, without altering the
      expression of thin-filament-associated regulatory proteins. 2. In single skinned
      myocytes, increased expression of beta-MHC did not significantly affect either
      maximal Ca2+-activated tension (P0) or the Ca2+ sensitivity of tension (pCa50).
      However, unloaded shortening velocity (V0) decreased by 80% due to increased beta
      MHC expression. 3. The kinetics of activation and relaxation were examined in
      skinned multicellular preparations using the caged Ca2+ compound DM-nitrophen and
      caged Ca2+ chelator diazo-2, respectively. Myocardium expressing 100% beta-MHC
      exhibited apparent rates of submaximal and maximal tension development (kCa) that
      were 60% lower than in control myocardium, and a 2-fold increase in the half-time
      for relaxation from steady-state submaximal force. 4. The time courses of cell
      shortening and intracellular Ca2+ transients were assessed in living,
      electrically paced myocytes, both with and without beta-adrenergic stimulation
      (70 nM isoproterenol (isoprenaline)). Thyroid deficiency had no affect on either
      the extent of myocyte shortening or the resting or peak fura-2 fluorescence
      ratios. However, induction of beta-MHC expression by thyroid deficiency was
      associated with increased half-times for myocyte shortening and relengthening and
      increased half-time for the decay of the fura-2 fluorescence ratio. Qualitatively
      similar results were obtained in both the absence and the presence of beta
      adrenergic stimulation although the beta-agonist accelerated the kinetics of the
      twitch and the Ca2+ transient. 5. Collectively, these data provide evidence that
      increased beta-MHC expression contributes significantly to the observed
      depression of contractile function in thyroid deficient myocardium by slowing the
      rates of both force development and force relaxation.

PMID- 9782170
TI  - Spontaneous electrical rhythmicity in cultured interstitial cells of cajal from
      the murine small intestine.
AB  - 1. Interstitial cells of Cajal (ICC) are pacemaker cells in the small bowel, and
      therefore this cell type must express the mechanism responsible for slow wave
      activity. Isolated ICC were cultured for 1-3 days from the murine small intestine
      and identified with c-Kit-like immunoreactivity (c-Kit-LI). 2. Electrical
      recordings were obtained from cultured ICC with the whole-cell patch clamp
      technique. ICC were rhythmically active, producing regular slow wave
      depolarizations with waveforms and properties similar to slow waves in intact
      tissues. 3. Spontaneous activity of c-Kit-LI cells was inhibited by reduced
      extracellular Na+, gadolinium, and reduced extracellular Ca2+. The activity was
      not affected by nisoldipine. Voltage clamp studies showed rhythmic inward
      currents that were probably responsible for the slow wave activity. The current
      voltage relationship showed that the spontaneous currents reversed at about +17
      mV. These observations are consistent with the involvement of a non-selective
      cation current in the generation of slow waves, but do not rule out contributions
      from other conductances or transporters. 4. A Ba2+-sensitive inwardly rectifying
      K+ current in c-Kit-LI cells that may be involved in slow wave repolarization and
      maintenance of a negative potential between slow waves was also found. Similar
      pharmacology was observed in studies of intact murine intestinal muscles. 5.
      Cultured ICC may be a useful model for studying the properties and pharmacology
      of some of the ionic conductances involved in spontaneous rhythmicity in the
      gastrointestinal tract.

PMID- 9782169
TI  - Role of cAMP-dependent protein kinase A in activation of a voltage-sensitive
      release mechanism for cardiac contraction in guinea-pig myocytes.
AB  - 1. Ionic currents and unloaded cell shortening were recorded from guinea-pig
      ventricular myocytes with single electrode voltage clamp techniques and video
      edge detection at 37 C. Patch pipettes (1-3 MOmega) were used to provide
      intracellular dialysis with pipette solutions. 2. Na+ currents were blocked with
      200 microM lidocaine. Contractions initiated by the voltage-sensitive release
      mechanism (VSRM) and Ca2+-induced Ca2+ release (CICR) in response to L-type Ca2+
      current (ICa,L) were separated with voltage clamp protocols. 3. Without 8-bromo
      cyclic adenosine 3',5'-monophosphate (8-Br-cAMP) in the pipette, small VSRM
      induced contractions occurred transiently in only 13% of myocytes. In contrast,
      large ICa,L-induced contractions were demonstrable in 100% of cells. 4. Addition
      of 10 or 50 microM 8-Br-cAMP to the pipette increased the percentage of cells
      exhibiting VSRM contractions to 68 and 93%, respectively. With 50 microM 8-Br
      cAMP, contractions initiated by the VSRM and ICa,L were not significantly
      different in amplitude. 5. 8-Br-cAMP-supported VSRM contractions had
      characteristics of the VSRM shown previously in undialysed myocytes. Cd2+ (100
      microM) blocked ICa,L and ICa,L contractions but not VSRM contractions. 8-Br-cAMP
      supported contractions exhibited steady-state inactivation with parameters
      characteristic of the VSRM, as well as sigmoidal contraction-voltage relations.
      6. Without 8-Br-cAMP in the pipette, contraction-voltage relations determined
      with steps from a post-conditioning potential (Vpc) of either -40 or -65 mV were
      bell shaped, with a threshold near -35 mV. With 50 microM 8-Br-cAMP in the
      pipette, contraction-voltage relations from a Vpc of -65 mV were sigmoidal and
      the threshold shifted to near -55 mV. Contraction-voltage relations remained bell
      shaped in the presence of 8-Br-cAMP when the Vpc was -40 mV. 7. H-89, which
      inhibits cAMP-dependent protein kinase A (PKA), significantly reduced the
      amplitudes of VSRM contractions by approximately 84% with 50 microM 8-Br-cAMP in
      the pipette. H-89 also significantly reduced the amplitudes of peak ICa, L and
      ICa,L contractions, although to a lesser extent. 8. We conclude that
      intracellular dialysis with patch pipettes disrupts the adenylyl cyclase-PKA
      phosphorylation cascade, and that the VSRM requires intracellular phosphorylation
      to be available for activation. Intracellular dialysis with solutions that do not
      maintain phosphorylation levels inhibits a major mechanism in cardiac excitation-
      contraction coupling.

PMID- 9782171
TI  - Validation of the [1,2-13C]acetate recovery factor for correction of [U
      13C]palmitate oxidation rates in humans.
AB  - 1. The validity of estimations of plasma fatty acid oxidation using tracers has
      often been questioned. The appearance of isotopic markers in breath CO2 is
      delayed and incomplete. Recently suggestions have been made that substantial
      amounts of tracer are incorporated into products of the tricarboxylic acid cycle
      (e.g. glucose, glutamine and glutamate) and that an acetate correction factor can
      be used to correct for tracer fixation. In the present study we investigated
      whether the appearance of 13CO2 during a separate infusion of [1,2-13C]acetate
      could be used for correction of [U-13C]palmitate oxidation rates in studies
      lasting <2 h and we quantified the appearance of tracer in the glutamine,
      glutamate and glucose pools of the body. 2. An infusion of either [1,2
      13C]acetate (0.104 micromol min-1 kg-1) or [U-13C]palmitate (0.013 micromol min-1
      kg-1) was given to eight male subjects and continued for 2 h at rest. In six
      subjects the infusion of [1,2-13C]acetate was repeated to determine
      reproducibility of the acetate recovery. 3. Fractional recovery in breath from
      [1,2-13C]acetate gradually increased during the infusion period at rest from 14.1
      +/- 0.6% at 60 min to 26.5 +/- 0.5% at 120 min after the start of the infusion.
      Intersubject coefficient of variance was 8.3 +/- 0.6% and intrasubject
      coefficient of variance of the acetate recovery tests was 4.0 +/- 1.5%. After 2 h
      of [1,2-13C]acetate infusion, 12.4 +/- 0.8 and 10.3 +/- 0.9% of infused 13C was
      incorporated in the glutamine and glutamate pools, respectively. 4. In
      conclusion, the [1,2-13C]acetate recovery factor can be used for correcting the
      rate of [U-13C]palmitate oxidation in infusing studies of 2 h in resting
      conditions. Failure to use this recovery factor leads to a substantial
      underestimation of the rate of plasma free fatty acid oxidation. The extent of
      label fixation could largely be explained by accumulation of tracer carbon in
      glutamine and glutamate, and the accumulation in glucose is negligible.

PMID- 9782172
TI  - The chronic effect of vascular endothelial growth factor on individually perfused
      frog mesenteric microvessels.
AB  - 1. Hydraulic conductivity (Lp) of the wall of perfused microvessels has
      previously been shown to be chronically increased 24 h after a 10 min perfusion
      with vascular endothelial growth factor (VEGF). In order to investigate this
      further, Lp and the effective oncotic pressure difference (f3DeltaPi) acting
      across the vessel walls was measured before exposure to VEGF and 24 h later after
      the mesentery had been replaced in the abdominal cavity. 2. Acute 10 min
      perfusion with VEGF did not chronically change f3DeltaPi despite chronically
      increasing Lp 6.8 +/- 1.2-fold. This suggests that pathways formed 24 h after
      perfusion with VEGF which increase hydraulic conductivity of the capillary walls
      have the same reflection coefficient as those present before VEGF. 3. Acute 10
      min perfusion with VEGF significantly increased the diameter of vessels after 24
      h by 48 +/- 13%. To determine whether this was due to changes in the compliance
      of the vessel wall, the distensibility of microvessels was measured before and 24
      h after perfusion with VEGF. The distensibility was increased 45 +/- 15% by VEGF
      but this was not great enough to account for the increase in diameter. 4. The
      chronic increase in Lp could be attenuated by inhibition of nitric oxide synthase
      with L-NAME. In addition, the chronic increase in permeability was correlated
      with the acute response to VEGF (r = 0.71, P < 0.01) suggesting that the acute
      and chronic changes may be related. 5. These results show that VEGF chronically
      increases Lp without affecting the oncotic reflection coefficient. This may be
      due to reduced pore path length, or increased small pore numbers, which are
      properties of fenestrated capillaries. They also show that VEGF increases
      microvascular distensibility and diameter.

PMID- 9782174
TI  - Contribution of Na+-H+ exchange to sodium reabsorption in the loop of henle: a
      microperfusion study in rats.
AB  - 1. The contribution of apical Na+-H+ exchange to sodium reabsorption in the thick
      ascending limb of the loop of Henle (TALH) in vivo was examined in anaesthetized
      rats by perfusing loops of Henle of superficial nephrons with solutions
      containing the Na+-H+ exchange inhibitor, ethyl isopropyl amiloride (EIPA). 2.
      Using a standard perfusate, no statistically significant effect of EIPA on net
      sodium reabsorption (JNa) was detected. However, when sodium reabsorption in the
      pars recta of the proximal tubule was minimized by using a low-sodium perfusate,
      EIPA reduced JNa from 828 +/- 41 to 726 +/- 37 pmol min-1 (P < 0.05), indicating
      that apical Na+-H+ exchange can make a small contribution to net sodium
      reabsorption in the TALH in vivo. This contribution appears to be dependent on
      the bicarbonate load, since an increase in the latter led to an enhancement of
      EIPA-sensitive sodium transport. 3. Addition of the Na+-K+-2Cl- cotransport
      inhibitor, bumetanide, to the low-sodium perfusate reduced baseline JNa to 86 +/-
      27 pmol min-1. In this setting, EIPA reduced JNa further, to -24 +/- 18 pmol min
      1 (P < 0.05), an effect similar to that seen in the absence of bumetanide. This
      finding argues against previous suggestions (based on in vitro evidence) that
      inhibition of the Na+-K+-2Cl- cotransporter leads to an increase in apical Na+-H+
      exchange in the TALH.

PMID- 9782173
TI  - Alkaline secretion by frog gastric glands measured with pH microelectrodes in the
      gland lumen.
AB  - 1. In the present work we have measured the pH of the secreted fluid within the
      gland lumen of isolated but intact gastric mucosa of Rana esculenta. Tissues were
      mounted in a double chamber allowing continuous perfusion of the mucosal and
      serosal compartment, and the measurements were made with double-barrelled pH
      glass microelectrodes inserted into the glands from the serosal surface under
      microscopic inspection. 2. During inhibition of H+ secretion by cimetidine (100
      microM) the luminal gland pH (pHgl) averaged 7.60 +/- 0.05 pH units (mean +/-
      s.e.m.; n = 35), a value significantly higher than bath solution pH (7.45 +/-
      0.02; P < 0.001) and also higher than intracellular pH of oxyntopeptic cells
      (pHi), which averaged 7.53 +/- 0.06 (n = 18). 3. Stimulation of acid secretion
      with histamine (500 microM) reversibly decreased pHgl to values which could be as
      low as 2.5. Together with electrophysiological criteria this response was
      routinely used to verify the proper location of the microelectrode tip within the
      gland lumen. 4. Stimulation with carbachol (100 microM) or pentagastrin (50
      microM) in the presence of cimetidine rapidly and reversibly increased pHgl by
      0.10 +/- 0.01 pH units (n = 24; P < 0.001) and 0.09 +/- 0.02 pH units (n = 6; P <
      0.05), respectively. 5. The observation that gastric gland fluid is more alkaline
      than the bath solutions and that carbachol or pentagastrin further alkalinize it
      strongly suggests that oxyntopeptic cells participate in gastric alkaline
      secretion at least under cholinergic stimulation.

PMID- 9782175
TI  - The arterial baroreceptor reflex of the rat exhibits positive feedback properties
      at the frequency of mayer waves.
AB  - 1. Modelling studies have led to the proposal that Mayer waves ( approximately
      0.4 Hz in rats) could result from a resonance phenomenon in a feedback control
      loop. In this study, we investigated the presence of a resonance frequency in the
      arterial baroreceptor reflex loop, i.e. a particular frequency at which arterial
      pressure feeds back positively to the baroreceptors. 2. Frequency responses of
      mean arterial pressure (MAP) to aortic depressor nerve (ADN) stimulation were
      studied in fifteen urethane anaesthetized, ventilated rats with cardiac autonomic
      blockade. The ADN was stimulated using rectangular trains of impulses (2 ms, 100
      Hz) delivered at frequencies ranging from 0.1 to 1 Hz. Phase angles between
      impulses and MAP were calculated using cross-spectral analysis based on a fast
      Fourier transform algorithm. 3. Rhythmic ADN stimulation induced regular MAP
      oscillations at the expected frequencies that were attenuated by alpha
      adrenoceptor blockade and abolished after ganglionic blockade. The relationship
      between impulse and MAP oscillations was characterized by a strong coherence and
      a positive phase shift at low frequencies, indicating that impulses led MAP with
      respect to the out-of-phase pattern. Deviation of the phase from the out-of-phase
      behaviour was mainly due to the presence of a fixed time delay ( approximately
      0.8 s) between ADN stimuli and MAP changes. Phase angles fell to zero at 0.42 +/-
      0.02 Hz. 4. In rats, the arterial baroreceptor reflex exhibits a resonance
      frequency close to the frequency of spontaneously occurring Mayer waves. The
      reflex therefore seems the most likely origin for the Mayer waves.

PMID- 9782176
TI  - Reflex control of splanchnic blood volume in anaesthetized dogs.
AB  - 1. In chloralose-anaesthetized, artificially ventilated dogs, the splenic pedicle
      was tied and the carotid sinuses were vascularly isolated and perfused at
      controlled pressures. In Series 1 experiments, the hepatosplanchnic circulation
      was perfused through the abdominal aorta with a tie on the aorta separating it
      from the caudal circulation, which was perfused through the femoral arteries. The
      two circulations were drained from cannulae in the inferior vena cava and the
      femoral veins, with a tie on the inferior vena cava separating the two. In Series
      2, the splanchnic circulation drained from the portal vein. In both series,
      inflows and outflows were measured and integrated to derive volume changes.
      Capacitance responses were assessed during constant flow, and capacitance plus
      passive responses were obtained during constant pressure perfusion. 2. In Series
      1, an increase in carotid sinus pressure (from 8 to 26 kPa) during constant flow
      and constant pressure perfusion increased hepatosplanchnic volume by 2.5 and 5.7
      ml (kg body weight)-1, respectively. The volume of the subdiaphragmatic
      circulation did not increase during constant flow, but during constant pressure
      it increased by 2.0 ml (kg body weight)-1. 3. In Series 2, increasing carotid
      pressure during constant flow and constant pressure increased the volume of the
      splanchnic circulation by 0.5 and 4.2 ml (kg body weight)-1, respectively. 4.
      These results confirm that carotid baroreceptor stimulation causes larger volume
      changes during constant pressure perfusion than during constant flow perfusion.
      Also, the active capacitance change in the splanchnic circulation is small in
      relation to the passive response. We propose that in dogs (following splenic
      ligation), the major active capacitance control is from the liver. However, large
      passive changes in splanchnic volume occur due to changes in flow.

PMID- 9782177
TI  - Electrocortical activity in fetal sheep in the last seven days of gestation.
AB  - 1. Electrocorticogram (ECoG) and myometrial electromyogram (EMG) were recorded
      continuously in chronically instrumented late gestation sheep fetuses (n = 9) to
      analyse: (1) 24 h ECoG patterns, (2) relationships between ECoG and myometrial
      contractility, and (3) 24 h ECoG patterns at the spontaneous onset of labour. 2.
      Spontaneous onset of labour was determined from the myometrial EMG. ECoG signals
      were purified by a denoising procedure of wavelet decomposition. High-voltage
      slow ECoG activity (HV) and low-voltage fast ECoG activity (LV) were determined
      mathematically, and HV-LV cycle periodicity was calculated by periodogram
      analysis. 3. Twenty-four hour rhythms were present in fetal ECoG HV-LV cycles in
      the 3-5 days prior to spontaneous onset of labour (P < 0.01). Cycle frequency was
      lower at 08.00-12.00 h and higher at 16.00-20.00 h (lights on at 07.00 h, lights
      off at 21.00 h). LV duration was longer at 20.00-24.00 h, and HV was shorter at
      16.00-20.00 h. No relationship was found between ECoG cycles and myometrial
      contracture cycles. Twenty-four hour ECoG rhythms disappeared 1 day before the
      spontaneous onset of labour. 4. ECoG patterns changed 7 to 4 h prior to
      spontaneous onset of labour, percentage of time spent and duration of HV ECoG
      increased, and percentage of time spent in LV decreased significantly. ECoG HV-LV
      cyclicity was reduced 4-5 h prior to spontaneous onset of labour, indicating that
      the altered fetal hormonal and blood gas environment around the spontaneous onset
      of labour alter fetal neural function.

PMID- 9782178
TI  - The effect of dopamine on lung liquid production by in vitro lungs from fetal
      guinea-pigs.
AB  - 1. The neuroendocrine system of the lungs has no clear function. However,
      previous studies of one of its products, somatostatin, have implicated it in lung
      liquid removal at birth. The present study extends this concept by investigating
      the effects of dopamine, a major product of this system, on lung liquid
      reabsorption. 2. The effects of dopamine on fetal lung liquid production and
      reabsorption were tested on in vitro lungs from fetal guinea-pigs of 60 +/- 2
      days of gestation (term = 67 days). Dopamine was placed in the outer bathing
      saline during the middle hour of 3 h incubations. Fluid movements across the
      pulmonary epithelium were monitored by a dye dilution method, and changes in
      rates over 1 h intervals were tested for significance by analysis of variance and
      regression analysis. 3. Dopamine was able to reduce fluid production or cause
      reabsorption (based on 42 preparations). Control preparations and those given 10
      8 M dopamine showed no significant changes; those given higher concentrations
      showed significant reductions in production or reabsorption (P < 0.025 to P <
      0.0005), according to dose (42.6 +/- 10.8% reduction at 10-7 M; 75.4 +/- 5.9%
      reduction at 10-6 M; 92.1 +/- 7.0% reduction at 10-5 M and 121.4 +/- 12.8%
      (reabsorption) at 10-4 M dopamine). The linear log dose-response curve (r = 0.99)
      showed a theoretical threshold at 1.7 x 10-9 M dopamine. 4. Effects were mediated
      through specific dopamine receptors (based on 78 preparations). Dopamine at 10-6
      M was tested together with each of three dopamine receptor antagonists at 10-5 M.
      The general dopamine receptor antagonist haloperidol and the more specific D2
      receptor blocker domperidone both abolished responses, but the D1 receptor
      antagonist SCH 23390 was without effect. This suggested that D2 dopamine
      receptors mediated the responses, and that responses were not due to conversion
      of dopamine to adrenaline or noradrenaline. 5. There was no evidence that
      responses involved amiloride-sensitive Na+ transport (based on 54 preparations).
      Apical amiloride at 10-6, 10-5 or 10-4 M, and the more specific Na+ channel
      blocker benzamil (10-5 M), had no effect on responses to dopamine, in contrast to
      their effects on responses to adrenaline in sheep. 6. It is suggested that
      internal release of dopamine by the neuroendocrine system of the lungs may
      influence lung liquid reabsorption at birth. This system, which also produces
      somatostatin, another agent active on lung liquid production, is maximally
      developed and activated at birth; it is also deficient in hyaline membrane
      disease.

PMID- 9782179
TI  - Changes in single motor unit behaviour contribute to the increase in contraction
      speed after dynamic training in humans.
AB  - 1. The adaptations of the ankle dorsiflexor muscles and the behaviour of single
      motor units in the tibialis anterior in response to 12 weeks of dynamic training
      were studied in five human subjects. In each training session ten series of ten
      fast dorsiflexions were performed 5 days a week, against a load of 30-40% of the
      maximal muscle strength. 2. Training led to an enhancement of maximal voluntary
      muscle contraction (MVC) and the speed of voluntary ballistic contraction. This
      last enhancement was mainly related to neural adaptations since the time course
      of the muscle twitch induced by electrical stimulation remained unaffected. 3.
      The motor unit torque, recorded by the spike-triggered averaging method,
      increased without any change in its time to peak. The orderly motor unit
      recruitment (size principle) was preserved during slow ramp contraction after
      training but the units were activated earlier and had a greater maximal firing
      frequency during voluntary ballistic contractions. In addition, the high
      frequency firing rate observed at the onset of the contractions was maintained
      during the subsequent spikes after training. 4. Dynamic training induced brief (2
      5 ms) motor unit interspike intervals, or 'doublets'. These doublets appeared to
      be different from the closely spaced (+/-10 ms) discharges usually observed at
      the onset of the ballistic contractions. Motor units with different recruitment
      thresholds showed doublet discharges and the percentage of the sample of units
      firing doublets was increased by training from 5.2 to 32.7%. The presence of
      these discharges was observed not only at the onset of the series of spikes but
      also later in the electromyographic (EMG) burst. 5. It is likely that earlier
      motor unit activation, extra doublets and enhanced maximal firing rate contribute
      to the increase in the speed of voluntary muscle contraction after dynamic
      training.

PMID- 9782180
TI  - Movement detection at the human big toe.
AB  - 1. To be detected, movements of the interphalangeal joint of the big toe must be
      greater than at other joints. This poor acuity may arise because the anatomy of
      the foot and ankle results in poor coupling between the toe and the muscles that
      operate it. To vary this coupling, the effect of ankle position on proprioceptive
      acuity at the toe was measured. 2. We measured proprioceptive acuity at the toe
      with the ankle in different positions and found that ankle plantarflexion did
      improve acuity. This implies that, with the ankle at mid-range or dorsiflexed,
      toe movement is inadequately transferred to muscle fascicles. 3. To determine
      actual changes in fascicle length of the toe extensor, movements of extensor
      hallucis longus near the toe and at the muscle-tendon junction were measured
      during surgical exposure in one subject. Ankle position greatly affected movement
      transfer from toe to muscle-tendon junction: no tendon movement was transferred
      with the ankle dorsiflexed, but all movement was transferred with the ankle
      plantarflexed. 4. When the relationship between joint rotation and muscle
      fascicle length measured in vivo was used to express the smallest detectable
      movements of the toe as proportional changes in muscle fascicle length, these
      detectable changes were similar to those at all other limb joints. This suggests
      that change in muscle fascicle length is of major interest to the nervous system.

PMID- 9782181
TI  - Effects of intracellular N+, M2+ and metabolites on C2+-activated K+ channels in
      pulmonary and ear arterial smooth muscle cells of the rabbit.
AB  - Hypoxic pulmonary vasoconstriction (HPV) is an important mechanism for matching
      the ventilation/perfusion ratio in the lung, but the signal transduction pathway
      through which hypoxia induces vasoconstriction remains unclear. We hypothesized
      that the decrease in K+ current induced by hypoxia is a key mechanism for HPV,
      and examined the effects of the substances which are expected to accumulate
      during hypoxia on the activity of large conductance Ca2+-activated K+ (BKCa)
      channels. Pulmonary and ear arterial smooth muscle cells were isolated from the
      rabbit using enzymatic digestion, and large conductance Ca2+-activated K+ current
      (IBK,Ca) was recorded in symmetrical K+ concentrations using the inside-out mode
      of the patch-clamp technique. Increasing the Na+ concentration on the
      intracellular side suppressed IBK,Ca dose dependently: 4.6, 20.9, 35.5 and 44.6 %
      reduction with 4, 8, 12 and 16 mM Na+, respectively. Mg2+ also reduced IBK,Ca,
      and the maximum reduction was obtained at 0.5 mM. Lactate, adenosine, ADP and ATP
      did not significantly affect IBK,Ca. There was no difference between pulmonary
      and ear arterial smooth muscle cells in their response to the above substances;
      this finding rules out modulation of BKCa channels by the various factors thought
      to accumulate during hypoxia as a major mechanism involved in the decrease in the
      K+ conductance of pulmonary arteries in hypoxia.

PMID- 9782182
TI  - Effects of peptide fragments of protein kinase C on isolated rat osteoclasts.
AB  - The intracellular mechanisms responsible for inhibition of osteoclast activity
      are of significant interest in the search for more effective ways of managing
      bone diseases associated with enhanced bone resorption. Previous studies have
      suggested that the protein kinase C (PKC) pathway is an important inhibitory
      second messenger in osteoclasts. We, therefore, investigated the effects of the
      synthetic peptide fragments, PKC(530-558) and (19-36), which correspond to parts
      of the catalytic and regulatory domains of PKC, on the activity of isolated
      osteoclasts. These fragments have been shown to activate and inhibit PKC,
      respectively, in biochemical studies employing isolated rat brain PKC, but have
      rarely been employed in studies of cellular activity. PKC(19-36), an enzyme
      inhibitor (PKC-I), had no effect by itself on osteoclastic bone resorption.
      However, PKC(530-558), a PKC activator (PKC-A), caused a dose-responsive
      inhibition of bone resorption, which was accompanied by a rapid and distinctive
      change in osteoclast morphology. This effect was reversible: (a) upon removal of
      PKC-A, (b) upon continuous exposure to this fragment for more than 36 h, or (c)
      in the presence of PKC-I. In conclusion, a short synthetic peptide fragment of
      PKC (PKC-A) significantly inhibits osteoclastic bone resorption; this, together
      with the fact that the inhibitory effect is abolished in the presence of PKC-I,
      provides further evidence for an important physiological role for the PKC pathway
      in the regulation of osteoclast activity. Selective activation of this pathway
      may have important therapeutic implications for the management of bone diseases
      associated with enhanced resorption.

PMID- 9782183
TI  - Depletion of acinar secretory granules in the ferret parotid gland: effects of
      substance P and vasoactive intestinal peptide.
AB  - The acinar cells of the ferret parotid gland are supplied with parasympathetic
      nerve fibres containing vasoactive intestinal peptide (VIP) and substance P. In
      this study intracarotid infusions of the two peptides (0.5-1.0 microgram kg-1 min
      1 of each for 40 min) in the pentobarbitone-anaesthetized ferret, treated with
      atropine and adrenoceptor antagonists, induced a loss of acinar secretory
      granules from this gland, by 32 % in response to VIP and by 46 % in response to
      substance P. Stimulation of the parasympathetic auriculo-temporal nerve (40 Hz,
      in the presence of adrenoceptor antagonists) caused a larger loss of acinar
      granules from the gland than stimulation of the sympathetic superior cervical
      ganglion (intermittently, 50 Hz for 1 s every 10th second, in the presence of
      atropine) over 40 min (52 % versus 10 %). A 27 % granular loss in response to
      parasympathetic stimulation followed upon atropinization. The parasympathetic
      response was not further diminished by the tachykinin antagonist Spantide ((d
      Arg1, d-Pro2, d-Trp7,9, Leu)-substance P). Thus, despite the large exocytotic
      response to the infusion of substance P, the parasympathetic non-adrenergic, non
      cholinergic secretion of storage granules seemed, under the present experimental
      conditions, to occur independently of the action of substance P.

PMID- 9782184
TI  - Triple projections of neurones located in S1 and S2 segments of the cat spinal
      cord to the C6 segment, the cerebellum and the reticular formation.
AB  - Electrophysiological investigation of neurones in sacral segments of the spinal
      cord was performed in alpha-chloralose-anaesthetized cats in order to establish
      whether at least some ascending tract neurones could diverge to three different
      centres located in the brainstem, the cerebellum or the spinal cord. Recordings
      of antidromic action potentials from cells in S1 and S2 segments were taken
      following stimulation of the contralateral gigantocellular nucleus, contralateral
      restiform body and ipsi- and contralateral grey matter of the C6 spinal segment.
      Antidromic responses allowed identification of several types of neurones that
      differed in their pattern of supraspinal or propriospinal projections. In
      eighteen out of a total of sixty-three neurones triple projections to all the
      above structures were found. In the majority of cells investigated their axons
      divided into two branches ascending both ipsi- and contralaterally in the lateral
      funiculi of the spinal cord. Their cell bodies were distributed in laminae VII
      VIII except for a minor group of neurones that projected to the C6 segment only,
      which were located in laminae V-VI. The latter group also displayed lower values
      of axonal conduction velocities. Comparison of conduction velocities in proximal
      and distal parts of axons revealed significant slowing in most, raising the
      possibility that additional collaterals were present to other spinal or
      supraspinal centres. Dual and triple projections from most cells in this study
      suggest that such a divergence may be a more common feature of ascending tract
      neurones than has been reported before.

PMID- 9782185
TI  - Regional differences in action potential characteristics and membrane currents of
      guinea-pig left ventricular myocytes.
AB  - Regional differences in action potential characteristics and membrane currents
      were investigated in subendocardial, midmyocardial and subepicardial myocytes
      isolated from the left ventricular free wall of guinea-pig hearts. Action
      potential duration (APD) was dependent on the region of origin of the myocytes (P
      < 0.01, ANOVA). Mean action potential duration at 90 % repolarization (APD90) was
      237 +/- 8 ms in subendocardial (n = 30 myocytes), 251 +/- 7 ms in midmyocardial
      (n = 30) and 204 +/- 7 ms in subepicardial myocytes (n = 36). L-type calcium
      current (ICa) density and background potassium current (IK1) density were similar
      in the three regions studied. Delayed rectifier current (IK) was measured as
      deactivating tail current, elicited on repolarization back to -45 mV after 2 s
      step depolarizations to test potentials ranging from -10 to +80 mV. Mean IK
      density (after a step to +80 mV) was larger in subepicardial myocytes (1.59 +/-
      0.16 pA pF-1, n = 16) than in either subendocardial (1.16 +/- 0.12 pA pF-1, n =
      17) or midmyocardial (1. 13 +/- 0.11 pA pF-1, n = 21) myocytes (P < 0.05, ANOVA).
      The La3+-insensitive current (IKs) elicited on repolarization back to -45 mV
      after a 250 ms step depolarization to +60 mV was similar in the three regions
      studied. The La3+-sensitive tail current, (IKr) was greater in subepicardial
      (0.50 +/- 0.04 pA pF-1, n = 11) than in subendocardial (0.25 +/- 0.05 pA pF-1, n
      = 9) or in midmyocardial myocytes (0.38 +/- 0.05 pA pF-1, n = 11, P < 0.05,
      ANOVA). The contribution of a Na+ background current to regional differences in
      APD was assessed by application of 0.1 microM tetrodotoxin (TTX). TTX-induced
      shortening of APD90 was greater in subendocardial myocytes (35.7 +/- 7.1 %, n =
      11) than in midmyocardial (15.7 +/- 3. 8 %, n = 10) and subepicardial (20.2 +/-
      4.3 %, n = 11) myocytes (P < 0.05, ANOVA). Regional differences in action
      potential characteristics between subendocardial, midmyocardial, and
      subepicardial myocytes isolated from guinea-pig left ventricle are attributable,
      at least in part, to differences in IK and Na+-dependent currents.

PMID- 9782186
TI  - Conduction velocity and gap junction resistance in hypertrophied, hypoxic guinea
      pig left ventricular myocardium.
AB  - The passive and active electrical properties of left ventricular myocardium were
      measured, using conducted action potentials and current clamp of isolated
      myocytes. The objective was to quantify changes of intracellular resistivity, Ri,
      during hypertrophic growth and the simultaneous imposition of cellular hypoxia.
      Ri was estimated from the time course of the rising phase of a conducted action
      potential using a solution of the two-dimensional cable equation. The thoracic
      aorta of guinea-pigs was constricted to induce left ventricular hypertrophy (LVH)
      and myocardium used 50 and 150 days post-operation. Conduction velocity increased
      in the earlier stage of LVH and declined in the later stage, compared with age
      matched controls. Hypoxia reduced conduction velocity in all experimental groups.
      Ri increased only in the later stage of hypertrophy (253 +/- 39 Omega cm to 544
      +/- 130 Omega cm) and was additionally increased by hypoxia in all groups (e.g.
      control myocardium 252 +/- 39 Omega cm to 506 +/- 170 Omega cm). The magnitude of
      the increase of Ri in hypertrophied, hypoxic myocardium can create conditions
      required to generate re-entrant arrhythmias.

PMID- 9782187
TI  - Interactions among iron, calcium, phosphorus and magnesium in the nutritionally
      iron-deficient rat.
AB  - We studied the development of nutritional iron deficiency 0, 10, 20, 30 and 40
      days after the intake of a semisynthetic diet lacking iron (diet 0) and the
      possible interactions with calcium, phosphorus and magnesium in both control rats
      and rats after 40 days of iron deficiency. During this period, iron deficiency
      was found to produce stress in the rats, as evidenced by high levels of cortisol
      in the serum. High levels of parathyroid hormone (PTH) were also found. There was
      a considerable increase in the absorption of calcium, phosphorus and magnesium,
      but the phosphorus and magnesium balance decreased and that of calcium remained
      practically unchanged, although there was an increase in calcium urinary
      elimination. Despite the noticeable degree of bone demineralization, which was
      evident in the femur, serum levels of calcium, phosphorus and magnesium remained
      constant. The present study shows that severe nutritional ferropenic anaemia
      provokes significant alterations in the metabolism of calcium, phosphorus and
      magnesium. We conclude that these alterations should be taken into account in the
      treatment of this pathology, given its prevalence and the fact that it may
      exacerbate other pathologies, particularly those related to the metabolism of
      calcium and phosphorus.

PMID- 9782188
TI  - Effect of glucose-dependent insulinotropic polypeptide on whole-body glucose
      utilization in sheep.
AB  - Four adult Corriedale sheep were used in an experiment divided into three parts.
      In part 1 a primed continuous infusion of [6, 6-2H2]glucose was infused for 7 h.
      The first 3 h was the control period, from 3 to 7 h glucose-dependent
      insulinotropic polypeptide (GIP) was infused, and from 5 to 7 h somatostatin was
      infused. Part 2 of the experiment was the same as for part 1 except that insulin
      was infused between 3 h and 7 h and GIP was infused between 5 and 7 h. Coincident
      with the insulin infusion, normal glucose was also infused at a variable rate in
      order to keep the plasma glucose at basal levels. In part 3 of the experiment
      [6,6-2H2]glucose was infused for 5 h and somatostatin was infused between 3 and 5
      h. Measurements of glucose turnover were made in the last 40 min of the control,
      GIP only, insulin only, somatostatin only, GIP plus somatostatin and GIP plus
      insulin infusion periods. Plasma insulin levels were reduced to the limit of
      detection by the somatostatin infusion; under such conditions whole-body glucose
      uptake should be entirely non-insulin-mediated (NIMGU). Expressing glucose
      disposal as glucose metabolic clearance rate demonstrated that elevated, but
      still physiological GIP levels had no effect on NIMGU but significantly increased
      insulin-mediated glucose uptake when plasma insulin levels were similar to levels
      typically observed after a meal. These results indicate that in sheep, GIP may
      enhance insulin action with respect to glucose disposal following a meal, but has
      no effect on glucose disposal pathways not responsive to insulin.

PMID- 9782190
TI  - Effects of arginine vasotocin, isotocin and melatonin on blood pressure in the
      conscious atlantic cod (Gadus morhua): hormonal interactions?
AB  - The effects of exogenous arginine vasotocin (AVT), isotocin (IT) and melatonin on
      the blood pressure of conscious Atlantic cod (Gadus morhua) were examined.
      Ventral aortic blood pressure (PVA) was recorded from a cannula inserted into the
      afferent branchial artery of the third gill arch. Dorsal aortic blood pressure
      (PDA) was recorded via a cannula implanted into the efferent branchial artery in
      the same gill arch. Each fish received two doses (10 and 50 ng kg-1) of AVT, IT
      and melatonin. AVT was also administered in combination with melatonin. Injection
      of 10 ng kg-1 AVT produced significant hypertension, especially in animals
      injected during the daytime. In contrast, the same dose of IT induced no
      significant change in either PVA or PDA. Administration of 10 ng kg-1 melatonin
      at night caused a long-lasting decrease in both parameters. Melatonin also
      inhibited the increase in blood pressure elicited by AVT. These results indicate
      that AVT, but not IT, is vasopressor in the cod. The effects of combined
      administration of melatonin and AVT show the antihypertensive action of melatonin
      in AVT-induced hypertension.

PMID- 9782189
TI  - Age-related changes in oxygen and nutrient uptake by hindquarters in newborn pigs
      during cold-induced shivering.
AB  - Newborn pigs rely essentially on shivering thermogenesis in the cold. In order to
      understand the rapid postnatal enhancement of thermogenic capacities in piglets,
      the oxygen and nutrient uptake of hindquarters was measured in vivo in 1- (n = 6)
      and 5-day-old (n = 6) animals at thermal neutrality and during cold exposure. The
      hindquarters were considered to represent a skeletal muscle compartment. Indirect
      calorimetry and arterio-venous techniques were used. The cold challenge (23 C at
      1 day old and 15 C at 5 days old for 90 min) induced a similar increase (+90 %)
      in regulatory heat production at both ages. Hindquarters blood flow was higher at
      5 days than 1 day old at thermal neutrality (26 +/- 3 vs. 17 +/- 1 ml min-1 (100
      g hindquarters)-1) and its increase in the cold was much more marked (+65 % at 5
      days old vs. +25 % at 1 day old). Oxygen extraction by the hindquarters rose from
      30-35 % at thermal neutrality to 65-70 % in the cold at both ages. The calculated
      contribution of skeletal muscle to total oxygen consumption averaged 34-40 % at
      thermal neutrality and 50-64 % in the cold and skeletal muscle was the major
      contributor to regulatory thermogenesis. Based on hindquarters glucose uptake and
      lactate release, carbohydrate appeared to be an important fuel for shivering.
      However, net uptake of fatty acids increased progressively during cold exposure
      at 5 days old. The enhancement in muscular blood supply and fatty acid
      utilization during shivering is probably related to the postnatal improvement in
      the thermoregulatory response of the piglet.

PMID- 9782191
TI  - Systolic coronary flow impediment in the dog: role of ventricular pressure and
      contractility.
AB  - The present study was planned to investigate the effect of left ventricular
      pressure and inotropic state on coronary arterial inflow in systole in the
      anaesthetized dog. A wide range of left ventricular systolic pressures, including
      the physiological range, were studied. Experiments were done under conditions of
      maximal vasodilatation and low perfusion pressure in order to avoid vascular
      autoregulative interference and to keep the microvascular pressure within the
      normal range. In five anaesthetized dogs, perfused with extracorporeal
      circulation system, ventricular volume was changed from 20 to 50 ml in steps of
      10 ml by filling an intraventricular latex balloon, and the related changes in
      left ventricular pressure and coronary flow were measured. The volume was then
      extended to 70 ml to obtain an overstretch which induced a transient decrease in
      cardiac contractility. During the period of low cardiac contractility the volume
      was brought back to 20 ml in steps of 10 ml. Systolic ventricular pressure
      changed with volume but was lower during the period of low contractility. For
      systolic pressures below 100 mmHg there was no significant relationship between
      pressure and coronary systolic flow, but the relationship shifted to higher flows
      during low contractility. For systolic pressures above 100 mmHg systolic coronary
      flow decreased significantly when systolic pressure increased. In this case the
      slopes of the relationships were not significantly different before and after the
      reduction in contractility. These findings suggest that for systolic pressures
      less than 100 mmHg (i.e. below the physiological range) the shielding effect of
      the contracting ventricle prevents the ventricular pressure from being
      transmitted in the myocardial wall. When systolic pressure exceeds 100 mmHg the
      shielding effect is overcome and the amplitude of the systolic flow reduction
      varies with ventricular pressure.

PMID- 9782192
TI  - Role of luminal volume changes in the increase in pulmonary blood flow at birth
      in sheep.
AB  - The mechanism by which pulmonary blood flow increases and pulmonary vascular
      resistance decreases after birth is not fully understood. The aim of this study
      was to simulate the decrease in lung volume caused by the onset of air-breathing
      at birth and determine whether it can duplicate the changes in pulmonary blood
      flow and vascular resistance that occur at this time. In chronically catheterized
      fetal sheep near term (145 days of gestation), fetal pulmonary arterial blood
      flow was measured, using coloured microspheres, before and after fetal lung
      liquid volumes were reduced from 52.2 +/- 2.7 to 21.2 +/- 1.6 ml kg-1. During the
      30 min period following the reduction in lung liquid volume, the pulmonary-to
      systemic arterial pressure difference decreased from 6.8 +/- 1.2 mmHg (pulmonary
      > systemic) to 1.6 +/- 0.5 mmHg. Reducing the volume of fetal lung liquid
      increased pulmonary blood flow from 59.1 +/- 10.5 to 204.2 +/- 40.4 ml min-1 (100
      g tissue)-1 and reduced pulmonary vascular resistance from 0.53 +/- 0.20 to 0.14
      +/- 0.04 mmHg min ml-1 (100 g tissue)-1. We conclude that a reduction in fetal
      lung liquid volume, which simulates the reduction in lung volume that occurs at
      birth, causes a 3- to 4-fold increase in pulmonary blood flow and a reduction in
      pulmonary vascular resistance of a similar magnitude. Thus, the reduction in lung
      volume associated with the lung changing from a liquid- to an air-filled organ,
      may partly account for the increase in pulmonary blood flow and decrease in
      pulmonary vascular resistance at birth.

PMID- 9782193
TI  - Differences in human antagonistic ankle dorsiflexor coactivation between legs;
      can they explain the moment deficit in the weaker plantarflexor leg?
AB  - The present study examined the hypothesis that the antagonistic ankle dorsiflexor
      coactivation level during maximum isometric voluntary plantarflexion (MVC) is a
      function of ankle angle. Six male subjects generated plantarflexion and
      dorsiflexion MVC trials at ankle angles of -15 deg (dorsiflexed direction), 0 deg
      (neutral position), +15 deg (plantarflexed direction) and +30 deg having the knee
      flexed at an angle of 90 deg. In all contractions surface EMG measurements were
      taken from tibialis anterior and soleus which were considered representative
      muscles of all dorsiflexors and plantarflexors, respectively. Antagonistic
      dorsiflexor coactivation was expressed as normalized EMG and moment. Calculations
      of the antagonistic dorsiflexor moment were based on the tibialis anterior EMG
      dorsiflexor moment relationship from contractions at 50, 40, 30, 20 and 10 % of
      the dorsiflexion MVC moment. In both legs dorsiflexor coactivation level followed
      an open U-shaped pattern as a function of ankle angle. Differences of 9 and 14 %
      (P < 0.05) were found in the measured net plantarflexion MVC moment between legs
      at ankle angles of -15 and +30 deg, respectively. No difference (P > 0.05) was
      found in the calf circumference between legs. Differences were found in the
      antagonistic dorsiflexor coactivation between legs at ankle angles of -15 and +30
      deg. In the weaker leg the antagonistic EMG measurements were higher by 100 and
      45 % (P < 0.01) and the estimated antagonistic moments were higher by 70 and 43 %
      (P < 0.01) compared with the weaker leg at -15 and +30 deg, respectively. This
      finding was associated with a decreased range of motion (ROM) in the weaker leg
      (14 %, P < 0.01), such that no difference (P > 0.05) was found in dorsiflexor
      antagonistic coactivation between legs at end-range ankle angles. The findings of
      the study (i) have to be taken into consideration when estimating musculoskeletal
      loads in the lower extremity, (ii) imply that stretching training can result in a
      stronger plantarflexion at end-range ankle angles through inhibition of the
      dorsiflexors, and (iii) imply a neural drive inadequacy during a plantarflexion
      MVC at end-range angles.

PMID- 9782194
TI  - The control of timing and amplitude of EMG activity in landing movements in
      humans.
AB  - The control of self-initiated falls from different heights was studied. The
      objective of the study was to investigate in a quantitative manner the modulation
      of EMG timing (i.e. onset from take-off and duration from onset to touch-down)
      and amplitude (before and after foot contact) as a function of fall height. The
      muscles studied were m. soleus and m. tibialis anterior. Kinematic (ankle joint
      angle) and kinetic (ground reaction force) variables were also measured. Six
      subjects took part in the experiments that consisted of ten landings from each of
      five heights (0.2, 0.4, 0.6, 0.8 and 1 m) onto a force platform. We found a
      consistent pattern of co-contraction before and after touch-down across the fall
      heights studied. In both muscles, the onset of pre-landing EMG activity occurred
      at a longer latency following take-off when landing from greater heights. The
      absolute EMG duration was affected to a lesser extent by increasing fall height.
      These findings suggest that the onset of muscle activity of the muscles studied
      prior to foot contact is timed relative to the expected time of foot contact. Pre
      and post-landing EMG amplitude tended to increase with height. Despite a
      doubling in the magnitude of ground reaction force, the amplitude of ankle joint
      rotation caused by the impact remained constant across heights. These findings
      suggest that the observed pattern of co-contraction is responsible for increasing
      ankle joint stiffness as fall height is increased. The attainment of an
      appropriate level of EMG amplitude seems to be controlled by (a) timing muscle
      activation at a latency timed from the expected instant of foot contact and (b)
      varying the rate at which EMG builds up.

PMID- 9782204
TI  - Use of antisense vectors and oligodeoxynucleotides in neuro-oncology.

PMID- 9782206
TI  - Cranial vault expansion using transcutaneously activated magnetic implants.
AB  - The technique of distraction osteogenesis has not been widely used in the
      treatment of problems 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. Thirty immature rabbits were studied.
      Twenty-six of the rabbits underwent operations. Each of the 26 had 2 magnets
      fixed to its skull: one on the left parietal bone and one on the right parietal
      bone. Incomplete circumferential osteotomies were then performed around each
      magnet on 13 of the rabbits. A head frame was attached to each animal. Head
      frames without magnets were placed on 6 of the rabbits (3 with osteotomy, 3
      without osteotomy) while 20 of the animals (10 with osteotomy, 10 without
      osteotomy) had 2 magnets mounted on the frames which were of opposite polarity to
      those implanted. The remaining 4 rabbits served as nonoperative controls. Six
      weeks later all of the animals were sacrificed. There were significant
      differences in the cranial volumes and contours between the groups of animals.
      Many of the differences were increased by coincident osteotomy. Associated
      histologic findings are described.

PMID- 9782205
TI  - Familial occurrence of an arteriovenous fistula with a giant perimedullary
      pseudoaneurysm of the thoracic spinal cord in 2 young siblings.
AB  - Two siblings, a sister at age 3 years and a brother (15 years later) at 4 years
      of age, both presented with similar clinical pictures consisting of back pain,
      progressive gait difficulty, lower extremity weakness and hyperreflexia. Imaging
      studies in both cases showed the presence of a perimedullary mass with expansion
      of the bony spinal canal at T10-T12. Angiography demonstrated almost identical
      vascular lesions that in each case was being fed by a single left-sided T8
      fistulous vessel that expanded into a giant perimedullary venous pseudoaneurysm.
      Each malformation was successfully obliterated using endovascular techniques,
      balloon occlusion of the feeding vessel in the first case and coil embolization
      of the pseudoaneurysm in the second. Following treatment the neurologic deficits
      resolved in both patients. These young siblings represent the first known case of
      familial occurrence of very similar giant perimedullary venous pseudoaneurysms of
      the thoracic spinal cord.

PMID- 9782207
TI  - Complications after selective posterior rhizotomy for spasticity in children with
      cerebral palsy.
AB  - Selective dorsal rhizotomy (SDR) has been shown to be an effective treatment for
      the spasticity of cerebral palsy, but few studies have addressed specifically the
      side effects of the procedure. A retrospective study was performed to determine
      the frequency and nature of complications in 158 children who had undergone SDR
      at British Columbia's Children's Hospital from 1987 to 1996. Intraoperative,
      preoperative (immediate postoperative until discharge at approximately 7 days)
      and postdischarge complications occurred in 3.8, 43.6 and 30% of patients,
      respectively. The most common intraoperative complication was aspiration
      pneumonia, which was experienced by 2 patients (1.3%). Perioperatively, sensory
      changes were found in 8.9% of the children, and transient urinary retention in
      4.4%. Complications after discharge included back pain starting more than 6
      months after surgery in 10.8%, sensory changes in 13.9%, and neurogenic bladder
      or bowel problems in 12.7%. Persistent sensory changes occurred in 3.8%, were not
      important functionally, and tended to occur in patients with the largest amount
      of dorsal root tissue cut. In 8 patients (5.1%), bladder and/or bowel dysfunction
      attributed to the SDR was present at the latest follow-up, although in only 2
      patients (1.3%) this dysfunction was a definite complication of the rhizotomy.
      The use of pudendal monitoring and/or cutting less than 50% of the S2 roots may
      have been associated with a lower incidence of long-term sphincter dysfunction.
      Data about the nature and frequency of complications may result in further
      modifications to the SDR procedure, and is critical for counseling about SDR and
      alternative options available for treatment of the child with spastic cerebral
      palsy.

PMID- 9782208
TI  - Chemotherapy in recurrent ependymoma.
AB  - Surgical resection with or without radiation therapy confers long-term remission
      in approximately half of the patients newly diagnosed with ependymoma.
      Chemotherapy has a limited role in the management of ependymoma. In newly
      diagnosed infants, chemotherapy is utilized as an attempt to defer radiation. The
      use of chemotherapy in older children has provided no conclusive benefit. The
      largest experience with chemotherapy in ependymoma has been in children with
      recurrent disease. In this section, we will analyze the principal institutional
      and cooperative group phase I, phase II, and phase III clinical trials utilizing
      single-agent and multiagent chemotherapy in patients with recurrent ependymoma.
      In addition, future directions relating to novel medical oncologic therapies will
      also be discussed.

PMID- 9782209
TI  - Nine-year-old female with neck pain.

PMID- 9782210
TI  - Atretic encephalocele.

PMID- 9782211
TI  - Concerning the article by Colak A et al. Pediatr Neurosurg 1997;27:208-210.
      Follow-up of children with shunted hydrocephalus.

PMID- 9782212
TI  - Is splitting of the vermis responsible for cerebellar mutism?

PMID- 9782213
TI  - Tuberculosis and HIV infection: a global perspective.
AB  - The incidence of HIV-associated tuberculosis has been increasing worldwide since
      the beginning of the AIDS epidemic, and is expected to increase even further
      during the foreseeable future, especially in developing countries. There is no
      doubt now that, in the presence of HIV infection, new-onset tuberculous infection
      progresses rapidly to clinically significant disease and the likelihood that
      latent tuberculous infection progresses rapidly to clinically significant disease
      and the likelihood that latent tuberculous infection will reactivate is
      enormously increased. The accelerating and amplifying influence of HIV infection
      is contributing to the increasing incidence of disease caused by multidrug
      resistant strains of Mycobacterium tuberculosis. Neither clinical features nor
      radiographic abnormalities reliably distinguish the majority of patients with HIV
      associated tuberculosis from those without HIV infection. Some persons with HIV
      infection, however, present with atypical manifestations of tuberculosis and
      these patients may be difficult to diagnose. Six months of daily or thrice weekly
      chemotherapy with the usual regimen of 4 then 2 antituberculosis drugs cures most
      patients, but many die during or after treatment of other AIDS-related
      complications.

PMID- 9782214
TI  - Lung diseases in the elderly.

PMID- 9782215
TI  - Prophylaxis of deep vein thrombosis in total hip replacement: which heparin and
      what duration?

PMID- 9782216
TI  - Is asthma in the elderly really different?
AB  - To examine the nature of asthma in the elderly, we compared older (group 1: 65
      years or older, n = 50) with younger patients (group 2: <40 years, n = 99) and to
      determine the influence of long-standing disease, elderly asthmatics with early
      onset (group A: onset before 40, n = 22) were compared with patients developing
      symptoms later in their lives (group B: onset after 40, n = 22). Blood
      eosinophilia and IgE value >/=100 IU/l were more frequent in younger patients.
      Short symptom-free periods were more frequent among older asthmatics (78.5 vs.
      45.4%, p < 0.001). Only 31.2% of older patients had only mild symptoms.
      Requirement of systemic steroids was higher in the elderly population. The worst
      FEV1 was lower in older patients (54.4 +/- 17.3 vs. 71.8 +/- 18.5%, p </= 0.001).
      Patients with early-onset asthma showed more frequently shorter symptom-free
      periods (93.3 vs. 53.3%, p <0.05), higher emergency admissions/year, and
      hospitalizations/year. Best FEV1 (group 1: 66.7 +/- 13.7% vs. group 2: 90.3 +/-
      15.1%, p < 0.005) and worst FEV1 (46.2 +/- 13.1 vs. 61.0 +/- 13.2%, p < 0.01)
      were lower in early-onset patients. A higher systemic steroid requirement, a
      lower best and worst FEV1, shorter symptom-free periods and a lesser proportion
      of patients with only mild symptoms were observed in patients older than 65 with
      early-onset asthma compared with those younger than 40 years. Elderly patients
      with a shorter duration of asthma were not different from young patients. Our
      study strongly suggests that severity of asthma and development of irreversible
      airflow obstruction depend on the duration of disease.

PMID- 9782218
TI  - Antiproliferative properties of human alveolar macrophages.
AB  - OBJECTIVE: The aim of our study was to determine whether macrophages from lung
      cancer patients could acquire antitumoral properties in an in vitro model.
      METHODS: We isolated macrophages from bronchoalveolar lavages performed in two
      groups of patients: patients with lung cancer and patients with lung infection.
      All patients were smokers. We used the inhibition of incorporation of 3H
      thymidine by U937 tumoral cells as an in vitro cytostatic assay. RESULTS: When
      stimulated by gamma interferon, alveolar macrophages either from lung cancer
      patients or from patients with lung infection induced cytostasis of proliferating
      U937 tumoral cells. This effect could be reproduced by using the supernatants of
      cultures of activated macrophages. When using optimal doses, gamma interferon
      showed an increased activity as compared with lipopolysaccharide. The combination
      of these two compounds was no more effective than gamma interferon alone in
      cancer patients. A macrophage/U937 tumoral cell ratio of 1/1 was sufficient to
      achieve a near-maximal cytostatic effect. CONCLUSIONS: Our results demonstrate
      that it is possible to activate, in vitro, alveolar macrophages from lung cancer
      patients by stimulation with gamma interferon. These macrophages acquire
      antiproliferative properties against a sensitive tumoral cell line.

PMID- 9782217
TI  - Inhalation by nebulization of albuterol-ipratropium combination (Dey combination)
      is superior to either agent alone in the treatment of chronic obstructive
      pulmonary disease. Dey Combination Solution Study Group.
AB  - Combination bronchodilator therapy for chronic obstructive pulmonary disease
      (COPD) potentially can provide increased benefit over single-agent therapy. The
      objective of this double-blind, randomized, positive-control trial was to
      determine the effectiveness of an albuterol-ipratropium solution aerosol
      combination (Dey combination solution, Dey LP, Napa, Calif., USA) compared with
      solution aerosols of both component medications administered alone in patients
      with COPD. The trial consisted of a 6-week, 3-period crossover phase followed by
      a 6-week parallel phase during which patients self-administered study medications
      by inhalation from a nebulizer. A total of 863 patients were initially randomized
      to each of the six possible treatment sequences of the three study medications in
      the crossover phase and received each study medication in turn for a 2-week
      period. Patients continued to receive the same treatment administered during the
      last 2-week period of the crossover phase for an additional 6 weeks in the
      parallel phase. Assessment of 1-second forced expiratory volume (FEV1) curves
      before and after dosing on the last day of each 2-week period indicated that the
      combination was superior to either single agent in peak effect and area under the
      curve up to 8 h after dosing (FEV1-AUC0-8), in both phases of the trial. The use
      of Dey combination during the crossover phase resulted in 24% more improvement in
      peak FEV1 than was seen with albuterol alone (p < 0.001), and 37% more than was
      seen with ipratropium alone (p < 0.001). Similarly, when examining FEV1-AUC0-8,
      Dey combination resulted in 30% more improvement than was seen with albuterol
      alone (p < 0.001), and 32% more than was seen with ipratropium alone (p < 0.001).
      The combination affords a convenient dosing regimen and incorporates enhanced
      benefit without compromising the safety profile of either component agent.

PMID- 9782219
TI  - Prolonged prophylaxis with unfractioned heparin is effective to reduce delayed
      deep vein thrombosis in total hip replacement.
AB  - The aim of this study was to assess the incidence of deep vein thrombosis (DVT)
      and pulmonary embolism (PE) until 45 days after elective total hip replacement
      (THR) and the efficacy of prolonged unfractioned heparin (UH) prophylaxis up to
      postoperative day 30. To this end 79 of 96 patients admitted consecutively to the
      University Hospital of Pisa for THR were randomly assigned to short- or long-term
      UH prophylaxis. Sixty-one patients completed the study: 28 of them received short
      term prophylaxis (subcutaneous UH 15,000 IU/24 h for 15 days) and 33 prolonged
      prophylaxis (subcutaneous UH 15,000 IU/24 h for 30 days). Lower limb phlebography
      was performed in all patients on day 45 after THR. DVT was demonstrated in 10
      (16.3%) cases after hospital discharge. Among them, 2 patients also had
      symptomatic PE. The incidence of DVT was 21.4% in short- and 12.1% in long-term
      UH-treated patients. The incidence of only proximal DVT was 17.8% in short- and
      3.0% in long-term UH-treated patients; although the difference was only close to
      significance (p = 0.085), the relative risk of developing proximal DVT was about
      six times greater in the former group of patients. We concluded that the risk for
      thromboembolism persists at least until 45 days after surgery in patients
      subjected to THR. Prophylaxis with UH given up to postoperative day 30 appears
      more effective and safer in reducing the delayed thromboembolic risk compared to
      prophylaxis with UH given up to discharge only.

PMID- 9782220
TI  - Acute effects of nebulized salbutamol on resting energy expenditure in patients
      with chronic obstructive pulmonary disease and in healthy subjects.
AB  - This study investigated the contribution of a single dose of salbutamol by
      nebulizer to the increased resting energy expenditure (REE) frequently found in
      patients with chronic obstructive pulmonary disease (COPD) (n = 22), in
      comparison with a younger (n = 15) and an older healthy (n = 10) control group.
      The rise in REE after nebulization of 5 mg salbutamol was significantly higher in
      younger (11.4%) compared to older healthy subjects (5.7%; p < 0.05) and patients
      with COPD (4.2%; p < 0.001), which also accounted for the increase in heart rate
      and the drop in the respiratory quotient. No differences in metabolic effects
      were found between older control subjects and patients with COPD. In conclusion,
      despite significant improvements in FEV1 and airway resistance, a significant
      rise in REE was observed in patients with COPD after nebulization of salbutamol.
      The metabolic effects of salbutamol were however not sufficient to explain
      totally the elevated REE seen in these patients.

PMID- 9782221
TI  - Dirithromycin concentrations in bronchial mucosa and secretions.
AB  - Since a high tissue penetration of dirithromycin (D) has been assessed in early
      studies, the aims of this study were to determine D concentrations in bronchial
      mucosa and secretions in patients suffering from an acute exacerbation of chronic
      bronchitis (AECB), to compare intra-individual bronchial mucosa and secretion
      concentrations and to relate bronchial concentrations of D and clinical efficacy.
      The main inclusion criteria were comprised of (1) AECB, defined by the presence
      of an increase in dyspnea, sputum production and change in sputum purulence, and
      (2) clinical indication of fiberoptic bronchoscopy allowing performance of
      bronchial biopsies. All patients were treated with a 500-mg once-daily D dose for
      5 days. Patients were randomly divided into three groups, according to sampling
      times (24, 48 and 72 h after the last dose). Tissue concentration analyses were
      performed by one blinded microbiologist (microbiological agar diffusion assay).
      The results showed: (1) 37 out of the 46 patients (80.4%) had a favorable
      response to treatment at the time of fiberoptic bronchoscopy (14 cured, 23
      improved); (2) bronchial mucosa concentrations were high in all groups, and (3)
      mean values at 24, 48 and 72 h after the last dose were respectively 6.51 +/-
      1.44, 6. 61 +/- 2.7, 5.67 +/- 1.02 mg.kg-1; no statistical difference was
      observed between the groups. In bronchial secretions collected simultaneously,
      concentrations were lower, i.e. 1.26 +/- 0.3, 0.61 +/- 0.12, 0.84 +/- 0.12.
      Significant associations were observed between bronchial mucosa and secretion
      concentrations (r = 0.71, p = 0.0001), and between clinical response and
      bronchial concentrations (p = 0.03, Kruskall-Wallis test). In conclusion, these
      results may confirm the clinical significance of tissue concentrations measured
      in bronchial tissues of patients with AECB.

PMID- 9782222
TI  - Relationship between inflammatory cells in bronchoalveolar lavage fluid and
      pathologic changes in the lung interstitium.
AB  - Bronchoalveolar lavage (BAL) is recognized as an important research tool for
      various lung diseases, but it is still uncertain whether inflammatory cells in
      BAL fluid (BALF) accurately reflect pathologic changes in the lung interstitium.
      We used a morphometric method to quantify the density of inflammatory cells in
      the lung interstitium by utilizing a computer-aided graphic analyzer and compared
      those findings with BALF results. Two types of animal models were studied, i.e.,
      endotoxemia (Escherichia coli endotoxin) and hypersensitivity pneumonitis
      (inhaled ovalbumin). Male Wistar rats were used; the right lungs were lavaged and
      the left lungs were prepared for morphometric study. In the endotoxemia model,
      the neutrophil fraction in BALF and the neutrophil density in the lung
      interstitium correlated significantly at 18 h (r = 0.81, p < 0.05) and 24 h (r =
      0.81, p < 0.05) but not at any other time points after injection. In the
      hypersensitivity pneumonitis model, the neutrophil fraction in BALF and the
      neutrophil density in the lung interstitium correlated significantly (r = 0.80, p
      < 0.05) only at 3 h after inhalation. The lymphocyte fraction in BALF and the
      lymphocyte density in the lung interstitium were correlated positively at 3 h (r
      = 0.83, p < 0.05), 1 day (r = 0.82, p < 0.05), 2 days (r = 0.67, p = NS), and 4
      days (r = 0.87, p < 0.05), but not at 6 days after inhalation. Our data suggest
      that neutrophil fraction in BALF does not reflect neutrophil populations in the
      lung interstitium except at the time of maximal neutrophil count in lung lavage.
      For lymphocytes in the hypersensitivity pneumonitis model, those in BALF and in
      the lung interstitium roughly correlate in the majority of measurements.

PMID- 9782224
TI  - Not a red herring.

PMID- 9782223
TI  - Pharmacologic characterization of latex extracts by isolated guinea pig tracheal
      tissue.
AB  - Latex manufacturing workers are exposed to a heterogeneous aerosol of organic
      compounds. Previous studies of latex workers involved in glove production
      indicate that these individuals are at risk of developing respiratory symptoms
      and impaired lung function. The effect of latex extracts on isolated guinea pig
      tracheal smooth muscles was studied using latex water-soluble extracts obtained
      at different stages of the industrial process. Latex extracts were prepared as a
      1:10 (w/v) solution. Dose-related contractions of nonsensitized guinea pig
      trachea were demonstrated using two latex extracts (latex 1 and latex 2). Latex 1
      was prepared from the native latex and latex 2 from a processed form of latex
      which was relatively free of soluble proteins. Pharmacologic studies were
      performed by pretreating guinea pig tracheal tissue with drugs known to modulate
      smooth muscle contraction: atropine, indomethacin, pyrilamine,
      nordihydroguaiacetic acid, acivicin, trimethobenzoic acid and capsaicin.
      Constrictor effects of the dust extracts were inhibited by a wide variety of
      these agents. Atropine consistently and strikingly reduced the contractile
      effects of these extracts. This observation may suggest an interaction of the
      extracts with parasympathetic nerves or more directly with muscarinic receptors.
      Inhibition of contraction by blocking other mediators was less effective and
      varied with the dust extract. Pretreatment with capsaicin did not change the
      constrictor effects of latex 1 but enhanced the effects of latex 2. Depletion of
      neuropeptides, however, did not reduce the constrictor effect. We suggest that
      latex extracts cause dose-related airway smooth muscle constriction by
      nonimmunological mechanisms involving a variety of airway mediators and possibly
      cholinergic receptors. This effect is not dependent on the presensitization of
      guinea pigs.

PMID- 9782225
TI  - Occupational asthma due to chromium.
AB  - We describe a 28-year-old subject employed as a roofer in a construction company
      since the age of 19, who developed work-related symptoms of a cough, shortness of
      breath, wheezing, rhinitis and headaches. A description of a usual day at work
      suggested that the symptoms worsened while he was sawing corrugated fiber cement.
      Baseline spirometry was normal, and there was a mild bronchial
      hyperresponsiveness to carbachol. A skin patch test to chromium was negative. A
      specific inhalation challenge showed a boderline fall in forced expiratory volume
      in 1 s (FEV1) after exposure to fiber cement dust. Exposure to nebulization of
      potassium dichromate (K2Cr2O7), at 0.1 mg.ml-1 for 30 min, was followed by an
      immediate fall by 20% FEV1. Simultaneously, a significant increase in bronchial
      hyperresponsiveness was demonstrated.

PMID- 9782226
TI  - The 'fragmented' scintigraphic lung pattern in pulmonary lymphangitic
      carcinomatosis secondary to breast cancer.
AB  - Pulmonary lymphangitic carcinomatosis (PLC) is an unusual presentation of diffuse
      infiltrative lung disease. In this report we present two cases secondary to
      breast cancer; the diagnosis was made by means of transbronchial lung biopsy or
      postmortem examination. The goal of this study was to analyze the scintigraphic
      pattern of pulmonary perfusion performed with technetium-99m macroaggregated
      albumin (99mTc-MAA) in the hope of achieving improved recognition of PLC and its
      subsequent diagnosis. Upon admission, both patients underwent routine clinical
      exams followed by chest X-rays. The second patient also underwent CT examination,
      and both were ultimately examined using pulmonary perfusion scintigraphy with
      99mTc-MAA. In the various exams performed, the most reliable and easily
      identified diagnostic finding turned out to be a characteristic 'fragmented' lung
      pattern revealed with the perfusion lung scan. Unfortunately, in both cases the
      patients' conditions rapidly worsened and death occurred shortly following
      scintigraphy. We were able to conclude that the recognition of the mentioned
      fragmented scintigraphic lung pattern may be useful in suspected PLC, whereas the
      nonspecific clinical presentation of this pathology makes diagnosis extremely
      difficult, with the most significant results being achieved through a comparison
      of scintigraphic and high resolution CT data.

PMID- 9782227
TI  - Large tension bronchogenic cyst in an adult mimicking the Swyer-James syndrome.
AB  - A case report of a large tension bronchogenic cyst in an adult that appeared as
      the Swyer-James/Macleod's syndrome is presented. Despite the thorough
      preoperative examinations the diagnosis was confirmed only after exploratory
      thoracotomy and histopathological study.

PMID- 9782228
TI  - Waldenstrom's macroglobulinemia with pulmonary amyloidosis.
AB  - We present a case of AL-type amyloidosis involving pulmonary parenchyma and hilar
      and mediastinal lymph nodes in a patient with Waldenstrom's macroglobulinemia.
      Direct infiltration of pulmonary parenchyma by lymphocytes and plasma cells is an
      important factor in the etiology and pathogenesis of pulmonary manifestations of
      the disease. Despite detailed examination, we did not find amyloid depositions in
      any extrapulmonary site.

PMID- 9782229
TI  - The phantom.

PMID- 9782230
TI  - Black holes, white dwarfs and supernovas: imaging after radiosurgery.
AB  - PURPOSE: To evaluate the imaging and pathological correlates of successful or
      risk-related stereotactic radiosurgery (SR). Methods and Materials. The ten-year
      Gamma Knife experience in 2,344 patients at the University of Pittsburgh was
      reviewed. In addition, the results or radiosurgery primate, rat, and mouse models
      were analyzed. Successful results and untoward complications were evaluated.
      RESULTS: Dose, volume, location and histology affected the imaging changes seen
      after SR. Imaging changes range from central loss of contrast ('black holes'),
      shrinkage with diffuse contrast uptake ('white dwarfs'), or stabilization or
      growth arrest. Limited pathological data indicates that the prevention of cell
      division coupled with vascular obliteration results in tumor control, whereas a
      progressive endothelial proliferative and obliterative response results in
      arteriovenous malformation (AVM) obliteration. Perilesional imaging changes,
      especially in vascular malformations, may reflect flow phenomena, interstitial
      edema, or profound reactive astrocytosis ('supernovas'). CONCLUSION: Imaging
      changes correlate with both success and risks of stereotactic radiosurgery;
      however, pathological correlates are limited. High resolution neurodiagnostic
      imaging provides the best quality control available to assess the response to
      stereotactic radiosurgery. In the future, additional molecular probes are
      necessary to assess the radiobiological effects of radiosurgery.

PMID- 9782231
TI  - Gamma knife radiosurgery for large volume brain tumors: an analysis of acute and
      chronic toxicity.
AB  - Gamma Knife radiosurgery is often used to treat intracranial tumors <4 cm
      (approximately 13.5 cm3) in mean diameter. Larger lesions are rarely treated
      because of the expectation that increasing target volume will increase toxicity.
      We retrospectively analyzed 35 patients with primary or metastatic brain tumors
      of more than 13.5 cm3 treated with the Gamma Knife. Only 3 (8.5%) patients
      developed acute clinical toxicity. Nine (25%) patients developed post-Gamma Knife
      radionecrosis based on imaging studies, with only 3 of these patients (9% of the
      study population) having clinical progression of symptoms. Necrosis was not found
      to be related to prescribed dose, treatment volume or number of treated
      isocenters. We found no undue toxicity from the treatment of large brain tumors
      with the Gamma Knife.

PMID- 9782232
TI  - The effectiveness and factors related to treatment results of gamma knife
      radiosurgery for meningiomas.
AB  - A retrospective analysis was conducted on 80 patients with intracranial mengiomas
      treated with Gamma Knife radiosurgery between 1993 and 1996. The purpose was to
      analyze the efficacy of the treatment and to assess appropriate treatment
      parameters. The results were assessed by regular MR examinations, and tumor
      volume was measured at 6-month intervals. Mean follow-up duration was 21 months
      (range 6-45 months). 63 meningiomas were at the skull base and 17 were distal
      from the skull base. Tumor volumes <5 ml (n=38), 5-10 ml (n=21), 10-15 ml (n=14),
      15-20 ml (n=7). The patients were divided into 3 groups according to the
      radiation dose. The groups were high-dose (peripheral dose 17-20 Gy, n=19),
      medium-dose (15-16 Gy, n=33) and low-dose (12-14 Gy, n=28) groups. A statistical
      method (Generalized Estimation Equation) was applied to compare treatment results
      in these groups with different doses and tumor volumes. The volume measurement at
      the latest follow-up showed 74% (59/80) meningiomas decreased in volume, 17%
      (14/80) had no tumor enlargement and 9% (7/80) had increased in volume. The
      increased volume was found more frequently in the patients with a short (6-12
      months) follow-up period. In this series, the tumors had 32&percnt reduction in
      average tumor volume at 3 years after radiosurgery. At the range of 12-20 Gy
      peripheral dose (PD), radiosurgery was effective to reduce tumor volume 0.7% per
      month (p<0.05). However, higher doses had no significant difference on tumor
      volume reduction (p>0.05). On the other hand, high-dose (PD>17 Gy) treatment was
      associated with a higher risk of temporary tumor swelling and the development of
      adverse radiation effects (AREs). The AREs detected on MR images occurred in
      (25/80) 31% patients. Only 6/25 AREs were symptomatic and 2 had neurological
      sequelae. Peripheral doses, tumor volumes and their locations had significant
      impacts on the ARE (p<0. 05). In conclusion, a peripheral dose of 15-16 Gy may be
      adequate for meningiomas with small volumes (<5 ml). In larger tumors (>10 ml) a
      lower PD is preferred (12-14 Gy). To avoid initial tumor swelling and ARE, high
      dose irradiation (PD>17 Gy) is not recommended for meningiomas larger than 5 ml.

PMID- 9782234
TI  - Dose volume histogram analysis of the gamma knife radiosurgery treating twenty
      five metastatic intracranial tumors.
AB  - Treating multiple brain metastatic sites in Gamma Knife radiosurgery is not
      uncommon. Most metastases can be treated with few or even one single shot.
      Occasionally we have patients returning for retreatment for different
      intracranial metastatic sites at different times. Dose distribution for these
      metastases are prescribed locally without considering the previous dose
      contribution. We present a study which simultaneously calculates the dose
      distribution of 25 randomly placed shots distributed inside the intracranial
      region. The Dose Volume Histogram (DVH) is plotted to study the coverage of the
      tumor sites and normal tissues. We have calculated ten DVH studies and show that
      50% of the brain volume receives less than 500 cGy for the maximum tumor dose of
      40 Gy, and the dose gradient is extremely steep. This DVH analysis shows that the
      Gamma Knife radiosurgery is a good treatment modality to control the local tumors
      while maintaining normal brain function, even for the large number of brain
      metastasis treated at different times.

PMID- 9782233
TI  - Cavernous sinus meningiomas--what is the strategy: upfront or adjuvant gamma
      knife surgery?
AB  - 43 patients with meningiomas of the cavernous sinus form the basis of this study.
      Two patients were treated with microsurgery alone, 17 patients were treated by
      Gamma Knife radiosurgery (GKRS) as a primary treatment modality, and 24 patients
      underwent a combined treatment of microsurgery followed by GKRS. Therefore, in 17
      patients the diagnosis rested on clinical and radiological criteria alone.
      Cranial nerve disorders (CND) related to open surgical treatment were infrequent
      in this material (3 of 13 patients) due to deliberate strategies of partial or
      subtotal resection aimed at sparing cranial nerves from surgical maneuvers. In
      contrast, 6 of 11 patients, admitted for GKRS from other institutions suffered
      from considerable CND after open surgery and showed only partial improvement
      after GKRS. In all GKRS cases, no radiation-related complications were seen after
      a follow-up of 18-62 months (mean 39 months). Moreover, in all cases tumor
      control was obtained with a stable tumor volume in 63%, reduction of volume in
      34.5% and a disappearance of tumor in 2.5%. GKRS is not only an additional
      treatment for meningiomas involving the cavernous sinus, but may be offered to
      the patient as an alternative primary treatment.

PMID- 9782235
TI  - Radiosurgery in lesional epilepsy: brain tumors.
AB  - The purpose of this study was to examine the effects of different doses of
      radiation to the brain tissue immediately adjacent to tumors which were
      associated with epilepsy. From April 1992 to December 1995, 26 patients with
      medically intractable tumor epilepsy (mean duration 6.9 years, range: 1-27 years)
      have been treated with Gamma Knife radiosurgery (GKRS). Clinical and imaging
      controls were available for 24 patients with a mean follow-up of 2.25 years
      (range: 1-4.4 years). Tumor control had been achieved in all patients. The
      patients were divided into two groups according to the volume of tissue outside
      the tumor which had received 10 Gy or more. This volume was assessed by measuring
      the ratio of the tumor and the ratio of the volume within the isodose containing
      10 Gy (10G/Tum ratio). 54 percent of all the 24 patients achieved an excellent
      result according to the Engel classification (class I or II). The patients were
      divided into two groups. In group I were 12 patients, and the 10G/Tum ratio was 3
      or less. In group II there were 12 patients and the 10G/Tum ratio was more than
      3. In group I the mean value for the 10G/Tum ratio was 2 (range 0.86 to 2.9). In
      group II the mean value of the ratio was 11.1 (range 3.13 to 63.2). In group I
      only 42% of patients achieved an excellent result compared with 66% in group II.
      Moreover, the location of the tumor had an effect on the results, in that
      temporal tumors were associated with excellent results in 64% of cases as opposed
      to 40% in extratemporal tumors. Finally, if the epilepsy had lasted for 2.5 years
      or less there were excellent results in 70% of patients, as opposed to 43%
      excellent results for patients who had suffered epilepsy for more than 2.5 years.

PMID- 9782236
TI  - Gamma knife treatment of acoustic neurinoma.
AB  - The results of treatment of acoustic neurinomas using Gamma Knife radiosurgery
      (GKR) during a 6-year period in our center were reviewed. Since May 7, 1990, we
      treated 88 cases of acoustic neurinoma with GKR. During a 52-month mean follow-up
      period, MRI was obtained in 63 patients. Reduction in tumor size occurred in 34
      (54%) cases, and another 27 (42.8%) tumors showed no change. The tumor control
      rate was thus 95%. Tumor size increased in 3 (4.8%) cases, but one case is still
      in early follow-up. Two cases were operated after GKR. Histological examination
      of the tumors removed at surgery 8 months after GKR were obtained. The
      examinations showed enlargement of nucleoli and cytoplasm and proliferation of
      endothelial cells due to delayed radiation changes. Post-GKR facial neuropathy
      was noted in 7 (8.8%) patients, of which 4 recovered during the follow-up period.
      The tumor volume, margin dose, number of isocenters and marginal isodose did not
      have any statistically significant relationship with the development of facial
      neuropathy. Transient trigeminal neuropathy were noted in 3 patients. Hearing was
      preserved in 2 of 3 hearing patients. In conclusion, our GKR results for acoustic
      neurinomas were very similar to the previously reported series, which makes GKR
      for acoustic tumors an excellent treatment modality for small- to medium-sized
      tumors with or without microsurgical tumor removal.

PMID- 9782237
TI  - Long-term complications following gamma knife radiosurgery of vestibular
      schwannomas.
AB  - Since its inception in 1969, Gamma Knife radiosurgery (GKR) for vestibular
      schwannomas has been documented as an efficient and safe procedure based on more
      than 8,000 treatments worldwide. The author's personal experience comprises 669
      treatments for patients with vestibular schwannoma between 1969-1997. This
      experience demonstrates long-term growth control, usually with shrinkage, in 95%
      of unilateral tumors. In the mid-1970s, early facial weakness occurred in 38% and
      facial numbness in 33%. This has gradually decreased to less than 2% in the
      1990s. Preservation of hearing (unchanged or almost unchanged) is currently
      achieved in 65 to 70%. Tinnitus is rarely changed by the treatment. The risks of
      intracranial bleeding, infection and CSF leak are avoided because of the
      noninvasive nature of the treatment. Hydrocephalus directly induced by the tumor
      occurred in 9.2% of patients. On the other hand, a treatment%related peritumoral
      reaction sufficient to block the CSF circulation and require shunt insertion was
      seen in only 1.4%. Based on experiences worldwide, the incidence of secondary
      neoplasia seems to be 0.1%. The effectiveness of GKR together with its low
      complication rate makes it a suitable treatment for anyone, regardless of age and
      general health. With few exceptions, schwannomas with an intracranial size of up
      to approximately 3 cm are suitable for GKR.

PMID- 9782238
TI  - Preservation of hearing in acoustic neuromas treated by gamma knife surgery.
AB  - 138 acoustic schwannomas were treated by Gamma Knife surgery from July 1992 to
      May 1994. Cases with neurofibromatosis were excluded because of differences in
      the patterns of growth and development of tumors in these cases. Hearing was
      evaluated by tonal and vocal audiometry and classified using the Gardner and
      Robertson score. 104 patients were observed at 3 years after treatment. Hearing
      studies, the relation of tumor volume to hearing, central and marginal dose,
      number of shots and preoperative brain-stem-evoked responses (BER) were all
      recorded. 70% of patients with normal hearing maintained a useful hearing, and
      50% of patients with useful hearing maintained serviceable hearing. No
      correlation was found between hearing preservation and tumor volume, central and
      marginal dose and number of shots. Gamma Knife surgery seems to be superior to
      microsurgery with regard to preservation of useful hearing.

PMID- 9782239
TI  - Stereotactic radiosurgery toxicity in the treatment of intracanalicular acoustic
      neuromas: the Seattle Northwest gamma knife experience.
AB  - Patients with acoustic neuromas have several treatment options. The appropriate
      individual treatment decision and expected control rates and risks for the
      individual techniques have been outlined in several texts [1-4, 6-8]. This
      article describes radiosurgery toxicity in those patients with acoustic neuromas
      who have intracanalicular disease. 52 patients with 54 acoustic neuromas were
      treated between September 1993 and April 1997. 14 tumors were intracanalicular
      lesions, with a mean diameter <1 cm and volume <1 cm3. Dose to the periphery of
      the intracanalicular lesion extension ranged from 12-18 Gy (mean 16 Gy). The
      margin isodose was 40-60% (mean 47%). 32 isocenters were used to treat the 14
      intracanalicular tumors (mean 2.3 isocenters per patient). At a mean follow-up of
      18 months (range 1-39 months), 12/12 or 100% of the intracanalicular lesions
      demonstrated regression or no change in size on subsequent imaging. The following
      acute side effects were observed posttreatment in intracanalicular tumors:
      diminished hearing 14%, facial neuropathy 43%, trigeminal neuropathy 21%, balance
      disorder 14%, dizziness 7%, and headache 7%. Facial and trigeminal neuropathy,
      balance disorder, dizziness, vertigo and headaches were more common in patients
      with intracanalicular tumors than those with an extracanalicular extension.
      Although it has been suggested that small acoustic neuromas (i.e. <1 cm3)
      tolerate doses of 18 Gy with acceptable toxicity, when the lesion is located in
      the auditory canal a lesser dose may be warranted to minimize potential side
      effects. For now, our center has established a protocol that limits radiosurgical
      stereotactic intracanalicular peripheral doses to 12 Gy until further toxicity
      studies have been collected and reviewed.

PMID- 9782240
TI  - Apoptosis following gamma knife radiosurgery in a case of acoustic schwannoma.
AB  - A 25-year-old woman with a large acoustic schwannoma underwent surgical excision
      18 months after Gamma Knife radiosurgery because of transient expansion of the
      tumor causing ataxia. Histopathologial investigation by the TUNEL method revealed
      the presence of some apoptotic cells. The findings were compared with findings
      from a control group of 7 operated cases where radiosurgery had not been used.
      There was no apoptosis found in any of these cases. In addition, another case
      which resulted in a regrowing tumor following Gamma Knife treatment also showed
      no apoptosis. These findings suggest apoptosis may be a possible mechanism in
      reducing tumor size following Gamma Knife radiosurgery.

PMID- 9782241
TI  - Four years' experiences in the treatment of pituitary adenomas with gamma knife
      radiosurgery.
AB  - To determine the tumor control rates and endocrinological responses after
      stereotactic radiosurgery for pituitary adenomas, we reviewed our experience in
      65 patients (40 men, 25 women) treated in the Gamma Knife during the last 4
      years. The mean age was 41.6 years (range 19-69 years). 43 patients had
      endocrinologically active tumors (20 growth hormone-secreting, 19 prolactin
      secreting and 4 ACTH-secreting adenomas). 22 had nonfunctioning adenomas. 39
      patients had a macroadenoma and 26 patients had a microadenoma. 33 patients
      underwent Gamma Knife radiosurgery for recurrent or residual tumors after
      microsurgery. 50 patients have had follow-up neuroimaging studies and/or hormonal
      evaluation. The follow-up period was 25.5 months (range 3 to 54 months). The
      margin of the tumor was incorporated within the 50 to 90% isodose. The mean
      number of isocenters was 3.8 and the mean marginal dose was 25.4 Gy (range 15 to
      36 Gy). 27 out of 40 patients (65.7%) showed decreased tumor volume to less than
      50% of the initial volume. In 17 out of 38 patients (44.7%) with
      endocrinologically active tumors, the hormonal level fell to within the normal
      range. Two patients had delayed complications: in one case there was pituitary
      insufficiency and in the other a visual disturbance. Gamma Knife radiosurgery
      seems to be effective adjuvant therapy for pituitary adenoma in selected cases.
      More long-term follow-up is required to evaluate the efficacy and side effects
      further.

PMID- 9782242
TI  - Pituitary tumors and gamma knife surgery. Clinical experience with more than two
      years of follow-up.
AB  - 30 patients with pituitary tumors were treated in our unit and followed for 26-45
      months. 14 patients had nonsecreting adenomas, 7 had acromegaly, 5 had
      prolactinomas, 3 had Cushing's disease. One patient had a choristoma of the
      pituitary stalk. The patient with a choristoma, 7 patients with nonsecreting
      adenomas, 4 with acromegaly, 1 prolactinoma and 3 with Cushing's disease had been
      operated by transsphenoidal microsurgery prior to Gamma Knife (GK) treatment.
      From this group, one patient with a nonsecreting adenoma and two with acromegaly
      had undergone fractional external radiotherapy after surgery. Stereotactic MRI
      localization had been used in all cases. All the tumors showed either a reduction
      in volume or cessation of growth; 85% of the patients with acromegaly showed
      normalization of growth hormone (GH) levels. Normalization of ACTH levels
      occurred in the 3 patients with Cushing's disease. All the patients with
      prolactinomas showed reduction of prolactin levels but normalization did not
      occur. However, in 3 cases the bromocriptine could be withdrawn. Deterioration of
      vision was not observed. One patient suffered transient paresis of the third
      cranial nerve that improved with steroids. Panhypopituitarism appeared in one
      case of Cushing's disease two years after the treatment. In the remaining cases
      there were no changes in their previous physiological pituitary function. We
      conclude that GK radiosurgery in pituitary tumors is an effective alternative to
      transsphenoidal microsurgery when compression of surrounding structures does not
      exist, and it can efficiently replace conventional irradiation.

PMID- 9782243
TI  - Pituitary adenomas: the effect of gamma knife radiosurgery on tumor growth and
      endocrinopathies.
AB  - Seventy-three patients have been treated with Gamma Knife radiosurgery (GKR) for
      pituitary adenomas. 12 had undergone surgery prior to GKR. Three had had previous
      radiation therapy. The prescription dose administered to the tumor margin ranged
      from 9 to 35 Gy. 65 patients were followed up for an average of 29 months. A
      slight expansion of tumor volume occurred in 3 cases. Otherwise, the tumor volume
      remained unchanged or decreased in the remainder. Endocrine changes were present
      in all except 3 cases. GKR was followed by a speedy decrease in raised serum
      hormone levels in the case of both growth hormone (GH)and adrenocortico-tropic
      hormone (ACTH). In 3 patients there was some visual deterioration associated with
      a slight increase in tumor volume. In 2 cases, the tumors were removed
      surgically. Some preliminary conclusions may be drawn. The dose required to
      correct an endocrinopathy may be higher than that required for control of tumor
      growth. The recommended prescription dose for endocrine-active adenomas may be
      more than 30 Gy. While clinical improvement may be noted in patients with raised
      serum prolactin levels (PRL), normalization of the endocrinopathy may be less
      readily achieved than in the case of raised GH and ACTH levels. Gamma Knife
      radiosurgery as a primary treatment of pituitary adenomas can be safe and
      effective.

PMID- 9782244
TI  - Short-term endocrinological results after gamma knife surgery of pituitary
      adenomas.
AB  - We report our preliminary results after the radiosurgical treatment of 25
      secreting pituitary adenomas with a mean follow-up of 20 months (range 6-36
      months). Fifteen acromegalic patients showed a decrease of 65% in mean growth
      hormone (GH) levels after 6 months and of 77% after 12 months. Only 3 patients
      (20%) are considered to be in remission (mean GH and IGF1 level into the normal
      range). A decrease of prolactin (PRL) was noted in 46% and 64% at 6 and 12 months
      after radiosurgery in 4 patients with prolactinomas. There was no case of PRL
      normalizaion. At present 3/4 patients have individual PRL levels slightly above
      the normal range. A normalization of Urinary Free Cortisol (UFC) was noticed in
      4/6 (66%) patients Cushing's disease within 6-12 months. Pituitary deficiency was
      noticed in this series in 4/25 patients (16%) who received subtotal or total
      pituitary irradiation for large postoperative remnants of secreting adenomas
      poorly defined on magnetic resonance imaging (MRI).

PMID- 9782245
TI  - Protection of visual pathway in gamma knife radiosurgery for craniopharyngiomas.
AB  - Craniopharyngiomas present a major challenge to Gamma Knife radiosurgery (GKRS)
      due to their proximity to the optic apparatus. Based on observations of the
      evolving tumoral change on MRI and clinical results, an optimization of the
      treatment strategy and dose selection is possible. From March 1993 to September
      1996, 21 patients with craniopharyngiomas were treated by GKRS. Every patient
      received stereotactic MRI exclusively for targeting and dose planning. The tumor
      and adjacent structures, including optic nerves, chiasm, and tracts were
      carefully identified and delineated on sagittal, coronal and axial films. The
      tumor volume ranged from 0.3 to 28 ml (average 9 ml). We purposefully apply
      multiple isocenters (average 9.1 shots) to create an isodose curve that covered
      the tumor optimally while sparing the optic pathway. The marginal dose prescribed
      was 9.5 to 16 Gy (50%). The maximal dose was 19 to 32 Gy. The maximal dose to the
      optic apparatus was 3.2 to 12.5 Gy. After GKRS, all patients were followed up
      clinically every month. MR studies were conducted every six months with the same
      techniques on the same scanner to investigate evolution of tumor volume and any
      adverse radiation effect. The follow-up period ranged from 6 to 40 months (mean:
      18.4, median: 19). All patients were followed more than 6 months. Nineteen out of
      21 cases (90.5%) achieved tumor control; that is, 18 tumor shrinkage (volume
      reduction: 15-95%) and 1 stabilized tumor growth. Among these 21 patients, 7 had
      improved visual acuity or visual field after GKRS, and the rest remained stable.
      Two patients developed mild T2 change on MRI without any endocrinological
      disturbance or visual impairment. Protection of the visual pathway can be secured
      by a sophisticated delineation on 3-dimensional stereotactic images with multiple
      shot dose planning. Craniopharyngiomas with tumor volume up to 25 ml were treated
      safely and effectively, because the dose to the optic apparatus was kept as low
      as possiby this strategy. Further follow-up is needed to determine the highest
      tolerable dose to surrounding critical structures and the long-term outcome of
      tumor control.

PMID- 9782246
TI  - Leksell gamma knife radiosurgery of the tumor glomus jugulare and tympanicum.
AB  - We have treated 14 patients with glomus tumor during the 4 years (of 1993 to
      1997) using Leksell Gamma Knife radiosurgery. The male: female ratio was 1:3.7,
      and the mean age 48.6 years (range 22-75 years). The mean tumor volume was 5.5
      cm3 (range 0.7-11.3 cm3). The mean maximum dose was 37.4 Gy (range 20-44 Gy). The
      mean margin dose was 19.4 Gy (range 10-25 Gy). In 3 patients, infrabasal spread
      of the tumor could not be delineated on peroperative stereotactic CT scans. As a
      result, this portion of the tumor was treated in 2 patients at a second stage
      using stereotactic MRI. Follow-up in 11 patients ranged from 6 to 42 months (mean
      20.5 months). Hearing on the affected side was further impaired in 3 patients.
      Tinnitus, vertigo and ataxia improved in 3 patients, headache and nausea in 2
      patients. Angiography after radiosurgery was performed in 3 patients. In one
      patient 12 months after the radiosurgery, pathological vascularisation had
      completely disappeared. In another patient pathological vascularisation was still
      present 22 months after the first stage, despite two-stage radiosurgery, although
      the tumor volume decreased 30%. In the last patient, vascularisation and tumor
      volume partially decreased 12 months after radiosurgery. The volume of the tumor
      decreased in 4 patients. No change in tumor volume has been observed in any of
      the other patients to date. Radiosurgery proves to be a safe treatment for glomus
      tumor with no acute morbidity. Because of its naturally slow growth rate, up to
      10 years follow-up will probably be necessary to establish the therapeutic
      effectiveness of radiosurgery for glomus tumor.

PMID- 9782247
TI  - Treatment of carcinoma of the hard palate with gamma knife radiosurgery.
AB  - The Gamma Knife radiosurgical treatment of two patients suffering from carcinomas
      of the hard palate is reported. A 67-year-old woman was treated with partial
      resection of an adenocarcinoma of the hard palate two years previously.
      Computerized tomographic imaging showed the tumor had grown (T4N1M0). The second
      patient, a 58-year-old woman, had a cauliflower-like tumor of the hard palate
      (T2N0M0). Pathological diagnosis obtained by needle biopsy was squamous cell
      carcinoma. These two patients underwent radiosurgical treatment with the Gamma
      Knife. A surface dose of 20 Gy was administered at the 35% isodose curve. These
      two patients were followed up for 18 and 15 months, respectively. Encouraging
      results were obtained. Further research is needed in order to validate this new
      treatment of carcinomas of the hard palate.

PMID- 9782248
TI  - Late cyst convolution after gamma knife radiosurgery for cerebral arteriovenous
      malformations.
AB  - Although many series of patients with cerebral arteriovenous malformations (AVMs)
      treated radiosurgically have been published, there has been little information on
      cysts appearing several years after irradiation. Herein, we discuss the
      incidence, mechanisms and predictability of late cyst formation based on our
      personal experiences, as well as reported patients. The incidence of this
      complication, though generally considered to be 0.5% or less, may be higher than
      assumed. Although a breakdown of the blood-brain barrier is likely to play a
      major role in the formation process, the hematoma cavity itself may have the
      potential to become a cyst. A radiation-induced lesion appearing several years
      after irradiation and persisting for several years thereafter may be a warning
      sign of late cyst formation. Long-term follow-up, particularly using neuroimaging
      techniques, is necessary even after the 'treatment goal' has been achieved.

PMID- 9782249
TI  - Gamma knife radiosurgery for hemangioblastomas.
AB  - Thirteen patients (11 males, 2 females) with cerebral hemangioblastomas (HABs)
      were treated with Gamma Knife radiosurgery (GKR). Four patients had multiple
      lesions in the brain. The remainder had a single lesion. The total number of
      lesions was 20. Eight cases had recurrent or residual HABs after surgery. In one
      case diagnosis was confirmed following surgical resection 22 months after GKR.
      One case was diagnosed by computed tomography (CT), magnetic resonance imaging
      (MRI) and digital subtraction angiography (DSA). Three patients had von Hippel
      Lindau (VHL) disease. The mean tumor diameter was 20 mm (range 7.5 to .55 mm).
      The mean margin dose was 18 Gy (range 12 to 24 Gy). In 5 cases, there was an
      improvement of symptoms and reduction in tumor volume. In 4 cases the tumor
      volume and clinical status remained unchanged. In 3 patients, there was clinical
      deterioration. The cause of this was an increase in tumor cyst volume in 2 cases.
      Subsequent surgery resulted in clinical improvement. In a third patient with
      multiple lesions, deterioration was the result of adverse radiation effects in
      the medulla oblongata. Three patients were subjected to post GKR-surgery with
      subsequent histopathology. In one, this was due to cyst expansion. In one, it was
      at the patient's insistence in the presence of a stable clinical and radiological
      picture. In a third patient with a temporal lobe tumor, it was because of late
      developing epileptic seizures. The histopathological findings in these patients
      showed varying degrees of small vessel thickening and occlusion together with
      loss of tumor cells. The observations varied in degree according to the time
      between GKR and the secondary operation. These findings indicate the
      effectiveness of the treatment. The reduction in vascularity suggests that GKR
      could make subsequent surgery less hazardous. The observations of this study
      suggest that while GKR is not adequately reliable for the control of HAB cysts,
      it can be an effective treatment for solid tumors, especially those in eloquent
      regions.

PMID- 9782250
TI  - Gamma knife radiosurgery as the first surgery for trigeminal neuralgia.
AB  - To evaluate the role of Gamma Knife radiosurgery as the first surgical therapy in
      the management of medically refractory trigeminal neuralgia, we reviewed outcomes
      on our first 23 patients who had radiosurgery as primary surgical therapy. These
      patients represented 19% of our overall series. Mean patient age was 66 years,
      and mean follow-up after radiosurgery was 12 months (range 5-33 months). For most
      patients, radiosurgery was performed because the patient had medical
      contraindications to open surgery. 14 patients had 70-Gy radiosurgery, and 9
      patients, 80 Gy. Radiosurgery was performed using a single 4 mm isocenter.
      Postoperative imaging 6 to 9 months following radiosurgery confirmed regions of
      enhancement at the radiosurgical target. Nine patients received 70 Gy, and 8
      patients had 80 Gy. 17 patients (74%) had an excellent result (total pain
      relief). Five patients (22%) achieved a good result (50-90% improvement). One
      patient had a poor result (4%) after 70-Gy radiosurgery and subsequently
      underwent microvascular decompression. No patient developed facial numbness or
      any other complication after Gamma Knife radiosurgery. Gamma Knife radiosurgery
      using 70 or 80 Gy targeted to the proximal trigeminal nerve proved to be a safe
      and effective primary surgical therapy for medically refractory trigeminal
      neuralgia. The overall response rate (96%) was similar to that obtained with
      other surgical therapies performed as a first procedure.

PMID- 9782251
TI  - Gamma knife radiosurgery for the treatment of trigeminal neuralgia.
AB  - One hundred and ten patients with trigeminal neuralgia were treated with the
      Gamma Knife using a single isocenter, the 4 mm secondary collimator helmet and a
      radiosurgical dose maximum of 70 or 80-Gy. The isocenter was placed at the
      trigeminal sensory root adjacent to the pons as identified on stereotactic MRI
      scans. Follow-up periods range from 4-49 months (mean 19.8 months). Initial pain
      relief was achieved in 95.5% of patients with typical trigeminal neuralgia
      symptoms, who had not had prior surgical intervention, and only 3.3% of these
      patients experienced recurrent pain during the follow-up period. Patients with
      atypical features to their pains or who had prior unsuccessful surgical attempts
      to relieve their pains achieved initial and long-term pain relief in 88 and 69%,
      respectively. Three patients (2.7%) developed delayed loss of facial sensation
      following treatment, but no other complications of any kind were noted. We
      believe that Gamma Knife radiosurgery is the safest and most effective form of
      treatment which is currently available for trigeminal neuralgia. We recommend
      early radiosurgical treatment of trigeminal neuralgia once the diagnosis is
      clearly established.

PMID- 9782252
TI  - Gamma knife treatment of trigeminal neuralgia: clinical and electrophysiological
      study.
AB  - Between October 1995 and October 1996, we treated 49 patients suffering from
      trigeminal neuralgia with Gamma Knife radiosurgery. There were 23 males and 26
      females. The mean age was 68 (range 38-94 years) The root of the trigeminal nerve
      close to brain stem was chosen as the target. The maximum dose was 70 Gy in 24
      cases and 80 Gy in 25 cases. A single shot with the 4-mm collimator was used. 13
      patients underwent Gamma Knife treatment of trigeminal nerve root without any
      previous surgical procedures. 31 patients suffered from an essential neuralgia
      (EN), while 7 had neuralgia related to multiple sclerosis (MS). Three had
      atypical neuralgia (AN) and 8 patients had postherpetic neuralgia (PN). Patients
      were divided into five groups according to pain reduction. The success rate of
      pain relief (excellent, very good and good responses) in these patients was: EN
      77% of patients, MS 43%, AN 33% and PN 38% of patients. Pain relief occurred
      after latent intervals of between 1 day and 8 months (median 2 months and mean
      2.8 months). Clinically detected complications after radiosurgery occurred only
      in the form of tactile hypesthesia in 6%. In a selected group of 18 patients, we
      observed slight electrophysiological changes in 2 patients (11%) after Gamma
      Knife treatment.

PMID- 9782254
TI  - Pallidotomy with the gamma knife: a positive experience.
AB  - 51 patients with medically refractory Parkinson's disease underwent stereotactic
      posteromedial pallidotomy between August 1993 and February 1997 for treatment of
      bradykinesia, rigidity, and L-DOPA-induced dyskinesias. In 29 patients, the
      pallidotomies were performed with the Leksell Gamma Knife and in 22 they were
      performed with the standard radiofrequency (RF) method. Clinical assessment as
      well as blinded ratings of Unified Parkinson's Disease Rating Scale (UPDRS)
      scores were carried out pre- and postoperatively. Mean follow-up time is 20.6
      months (range 6-48) and all except 4 patients have been followed more than one
      year. 85 percent of patients with dyskinesias were relieved of symptoms,
      regardless of whether the pallidotomies were performed with the Gamma Knife or
      radiofrequency methods. About 2/3 of the patients in both Gamma Knife and
      radiofrequency groups showed improvements in bradykinesia and rigidity, although
      when considered as a group neither the Gamma Knife nor the radiofrequency group
      showed statistically significant improvements in UPDRS scores. One patient in the
      Gamma Knife group (3.4%) developed a homonymous hemianopsia 9 months following
      treatment and 5 patients (27.7%) in the radiofrequency group became transiently
      confused postoperatively. No other complications were seen. Gamma Knife
      pallidotomy is as effective as radiofrequency pallidotomy in controlling certain
      of the symptoms of Parkinson's disease. It may be the only practical technique
      available in certain patients, such as those who take anticoagulants, have
      bleeding diatheses or serious systemic medical illnesses. It is a viable option
      for other patients as well.

PMID- 9782253
TI  - Effect of gamma knife on secondary trigeminal neuralgia.
AB  - The following study was conducted to evaluate the results of Gamma Knife
      stereotactic radiosurgery in the management of secondary trigeminal neuralgia. 53
      patients suffering from secondary trigeminal neuralgia were studied and the
      results reported. We defined four therapeutic groups: group I correspond to
      essential trigeminal neuralgia. The primary aim was tumor control in group IV and
      pain cessation in group III and II (visualization of the fifth nerve root was
      possible in group II but not in group III). The target dose of the radiosurgery
      used in the current study varied from 20 to 40 Gy in group III and IV and from 70
      to 90 Gy in group I and II. At short-term follow-up, 37 patients (74%) were pain
      free, 9 patients (18%) were improved (50%-90% relief) and only 4 patients (8%)
      experienced treatment failure. Among the patients with early treatment success,
      10 patients experienced a complete recurrence of pain in the four succeeding
      years, and 11 initially pain-free patients deteriorated to partial pain relief.
      The median time to pain relief was three months (range 1 day to 1 year). The mean
      follow-up was 32 months (range 7 to 60 months). No patient developed increased
      facial pain or deafferentation pain. Among the 53 patients, only two exhibit a
      slight facial hypesthesia and one patient described motor fasciculation related
      to Gamma Knife treatment. In our experience Gamma Knife surgery appears a safe
      and effective method for the treatment of secondary trigeminal neuralgia.

PMID- 9782255
TI  - Treatment of cerebral radionecrosis by hyperbaric oxygen therapy.
AB  - Clinically observed adverse radiation effects (ARE) are rather uncommon, but
      modern imaging reveals that they are more common after radiosurgery than
      previously believed. Little is known about the pathogenesis, and current
      treatment is mostly empirical. The benefit of hyperbaric oxygen therapy (HBO) on
      radiation-induced bone and soft tissue necrosis is known in lesions in the
      maxillofacial area, the mouth and in the head and neck. HBO raises the tissue pO2
      and initiates a cellular and vascular repair mechanism. This forms the basis for
      the hypothesis that it might also help alleviate the results of cerebral
      radionecrosis. This study is a preliminary attempt to test this hypothesis. Two
      patients with arteriovenous malformations (AVMs) were chosen for the study. They
      had been treated with Gamma Knife radiosurgery (GKRS) and had developed imaging
      signs consistent with ARE. They were treated by breathing 100% oxygen at 2.5
      atmospheres absolute (250 kPa) in sessions of 60 minutes per day. This treatment
      was repeated 40 times in cycles of ten sessions. Both responded well to HBO, one
      lesion disappeared and the other was reduced significantly in size. No adjuvant
      steroids were given. These results give evidence that HBO has a potential value
      in treating ARE but further experience will be needed to confirm its definite
      benefit.

PMID- 9782256
TI  - Effect of gamma knife radiosurgery on rat brain sodium channel subunit mRNA
      expression.
AB  - Several lines of evidence underscore a possible and delayed antiepileptic effect
      of Gamma Knife irradiation. This effect could be related to structural and
      molecular changes. Since voltage-gated Na+ channels (NaChs) play a crucial role
      in neuron excitability, we studied the effect of Gamma Knife (GK) irradiation on
      the distribution of Na+ channel (NaCh) subunit mRNAs in rat brains. A left side
      irradiation was performed in rats using a stereotactic device adapted for GK
      radiosurgery. A dose of 100 Gy was administered with the 4 mm collimator. The
      left dentate gyrus and thalamus coordinates were based on De Groot's rat
      stereotactic atlas. The isodose curve distribution was calculated with the dose
      planning software used in Gamma Knife and superimposed on the target. Na+
      channels alpha unit and mRNAs (subtype II and subtype III) expression was studied
      1 hour, 30 days and 60 days later. We used non-radioactive in situ hybridization
      with subtype-specific digoxigenin-labeled cRNA probes. Labeling intensity was
      evaluated with a densitometric analysis of digitized images from the control side
      (right) and lesioned side (left) in each rat. No morphological changes were
      observed one hour after GK irradiation. 30 days later, the upper thalamic nuclei
      exhibited a few necrotic regions associated with gliosis. In contrast, no lesions
      were observed in the hippocampus. 60 days later, the necrotic region involving
      thalamic nuclei was enlarged. NaCh II and III mRNAs expression did not appear to
      be modified after GK at the three times studied here. In particular, neurons
      surrounding the GK necrosis continued to express high levels of NaCh mRNAs. Thus,
      regulation of NaCh II and III subtypes do not appear to explain the functional
      antiepileptic effect of GK.

PMID- 9782257
TI  - 'Tweaked' GammaPlan for target volume measurement in non-fiducial based images: a
      simple routine for follow-up assessment.
AB  - The GammaPlan provides accurate estimation of target volume. However, a
      stereotactic frame and fiducials are required. At follow-up MR/CT, fiducials are
      no longer available. Surgeons rely on visual impression, 2-D measurements, or
      other methods to estimate the volume of the treated targets. These methods are
      not objective and may give rise to misleading conclusions. By modifying the image
      header files of GammaPlan version 3, it is possible to scale the images which are
      not acquired with stereotactic fiducials. The target is then mapped and its
      volume measured as usual. The target volumes in 7 patients were measured by the
      tweaked GammaPlan and compared with volume measurements using the standard
      version. The mean error was less than 2%. In a separate study, phantom syringes
      with known volumes of water were used for MR imaging. The tweaked version again
      gave accurate volume estimation of the phantom syringes with a less than 5% error
      for most cases. This method has subsequently been used in all Gamma Knife follow
      up cases. Significant volume changes have been detected where conventional
      assessment showed no apparent change. Moreover, such volume changes correlated
      with clinical improvement or deterioration. It is recommended that all Gamma
      Knife users report tumor response by volume change. Our method is simple,
      reliable and does not require additional cost.

PMID- 9782258
TI  - Neutralization of MHV-A59 by soluble recombinant receptor glycoproteins.
AB  - The interaction of viruses with specific receptors is an important determinant of
      viral tissue tropism and species specificity. Our goals are to understand how
      mouse hepatitis virus (MHV) recognizes its cellular receptor, MHVR, and how post
      binding interactions with this receptor influence viral fusion and entry. Murine
      cells express a variety of cell surface molecule in the biliary glycoprotein
      (Bgp) family that are closely related to the MHVR. When these proteins are
      expressed at high levels in cell culture, they function as MHV receptors. We used
      a baculovirus expression system to produce soluble recombinant murine Bgp
      receptors in which the transmembrane and cytoplasmic domains have been replaced
      with a six-histidine tag. The soluble glycoproteins were purified to apparent
      homogeneity and shown to react with antisera to the native receptor. We compared
      the virus neutralizing activities of various soluble receptor glycoproteins.
      Soluble MHVR [sMHVR(1-4)] had 10-20 fold more virus neutralizing activity the
      soluble protein derived from the Bgp1b glycoprotein [sBgp1b(1-4)], from MHV
      resistant SJL mice. The sMHVR(1-4) glycoprotein was 60-100 fold more active than
      a truncated receptor molecule containing only the first two immunoglobulin-like
      domains, sMHVR(1,2). The observation that sMHVR lacking domains 3 and 4
      neutralizes MHV-A59 very poorly suggests that these domains may influence virus
      binding or subsequent steps associated with neutralization.

PMID- 9782259
TI  - Isolation and characterization of murine coronavirus mutants resistant to
      neutralization by soluble receptors.
AB  - Murine coronavirus mutants resistant to neutralization with soluble receptors
      were isolated to study the receptor-binding site on the S proteins since such
      mutants were expected to have mutations in an important site for receptor
      binding. We have isolated five soluble receptor-resistant (srr) mutants which had
      mutations of a single amino acid at 3 different positions in S protein. Srr
      mutant 11 with an amino acid change at position 65 (Leu to His) in the S1 subunit
      showed an extremely reduced binding by virus overlay protein blot assay. However
      srr mutants with a mutation at 1114 (Leu to Phe) (srr mutants 3, 4 and 7) or 1163
      (Cys to Phe) (srr mutant 18) in the S2 subunit had receptor-binding activity
      similar to that of wild type cl-2. These results suggest that an amino acid at
      position 62 located in a conserved region among MHV strains is in particular
      important for receptor binding. We also discuss why srr mutants with a mutation
      in S2 showed high resistance to neutralization by soluble receptor, irrespective
      of their binding to MHV receptors.

PMID- 9782260
TI  - Mutational analysis of fusion peptide-like regions in the mouse hepatitis virus
      strain A59 spike protein.
AB  - The coronavirus peplomer protein S is responsible for attachment and fusion
      during viral entry as well as for the induction of cell to cell fusion. While
      several regions within S have been shown to influence the ability to induce
      fusion, the region of the protein actually responsible for fusion, the fusion
      peptide, has not yet been identified. We identified two hydrophobic peptides
      (peptides #1 and #2) within MHV-A59 S2 as possible fusion domains. This was based
      on hydrophobicity, conservation among coronavirus S proteins and the prediction
      of a sided helix conformation. Using site directed mutagenesis and an in vitro
      cell to cell fusion assay we showed that substitution of hydrophobic amino acids
      with charged amino acids, within the predicted hydrophobic face of either of
      these two peptides eliminated fusion. Within peptide #1 substitution of the same
      hydrophobic amino acids with other hydrophobic amino acids or substitution of
      polar amino acids with charged or polar amino acids had little effect on fusion.
      Thus peptides #1 and #2 remain likely candidates for the MHV fusion peptide. A
      third previously identified peptide within S2 (Chambers et al., 1990) is unlikely
      as a fusion peptide as it is not well conserved among coronaviruses and
      substitution within the hydrophobic face with charged amino acids does not effect
      fusion.

PMID- 9782261
TI  - Interactions of enterotropic mouse hepatitis viruses with Bgp2 receptor proteins.
AB  - Enterotropic mouse hepatitis virus (MHV) infections are limited to the intestinal
      mucosa, rarely disseminate to other tissues and cause disease only in neonatal
      mice. The role of virus-host cell receptor interactions in the limited tissue
      tropism of enterotropic MHV infections is unclear. Previous studies have shown
      that enterotropic MHV-Y can infect BHK cells stably transfected with either the
      MHVR or the mmCGM2 receptor gene. In contrast, enterotropic MHV-RI infects BHK
      cells stably transfected with the MHVR but not the mmCGM2 receptor gene. Studies
      to determine whether MHV-Y and -RI can utilize the Bgp2 receptor isoform were
      performed. Both MHV-Y and -RI infected Vero cells transiently transfected with
      the Bgp2 receptor gene, though only MHV-Y infected CHO cells stably transfected
      with the Bgp2 receptor gene. Additionally, pretreatment with anti-MHVR monoclonal
      antibody (CC1) did not prevent MHV-Y and -RI infection of CMT93 cells. In
      contrast, pretreatment with CC1 prevented MHV-A59 infection of CMT93 cells. It is
      likely that MHV-Y and -RI use the Bgp2 receptor to infect CC1 pretreated CMT93
      cells, since CMT93 cells are known to possess high levels of the Bgp2 receptor
      mRNAs, but it is also possible that they use an unidentified receptor.

PMID- 9782262
TI  - Virus-receptor interactions and interspecies transfer of a mouse hepatitis virus.
AB  - Molecular mechanisms regulating virus xenotropism and cross-species transmission
      are poorly understood. Host range mutants (MHV-H2) of mouse hepatitis virus (MHV)
      strains were isolated from mixed cultures containing progressively increasing
      concentrations of nonpermissive Syrian baby hamster kidney (BHK) cells and
      decreasing concentrations of permissive murine astrocytoma (DBT) cells. MHV-H2
      was polytrophic, replicating efficiently in normally nonpermissive BHK cells,
      Syrian and Chinese hamster (DDT-1 and CHO) cells, human adenocarcinoma (HRT),
      primate kidney (VERO) and in murine 17Cl-1 cell lines. Little if any virus
      replication was detected in feline kidney (CRFK), and porcine testicular (ST)
      cell lines. To study the effects of xenotrophic spread on virus receptor
      interactions in the original host, murine DBT cells were pretreated with a
      monoclonal antibody (MAb) CC1, directed against the MHV receptor, MHVR, a biliary
      glycoprotein (Bgp1a). Under treatment conditions that completely ablated the
      replication of the parental MHV strains, CC1 antireceptor antibodies did not
      block MHV-H2 replication. Following expression of MHVR in normally nonpermissive
      ST and CRFK cells, infection with the parental MHV strains, but not MHV-H2 was
      observed. To characterize the molecular basis preventing the interaction between
      MHV-H2 and MHVR, revertants of MHV-H2 (MHV-H2R6, MHV-H2R11) were isolated
      following a persistent MHV-H2 infection in DBT cells. These revertant viruses
      efficiently recognized MHVR, however infection of murine cells was resistant to
      MAb CC1 blockade. In addition, MHV-H2 and the revertant viruses efficiently
      recognized other Bgp receptors for docking and entry. These data suggest that
      interspecies transfer may remodel normal virus-receptor interactions that may
      result in altered virulence, tropism or pathogenesis in the original host.

PMID- 9782264
TI  - Obtention of porcine aminopeptidase-n transgenic mice and analysis of their
      susceptibility to transmissible gastroenteritis virus.
AB  - To obtain a laboratory animal model for transmissible gastroenteritis virus
      (TGEV) infection, transgenic mice (Tg) were produced by introducing two porcine
      aminopeptidase-n (APN) cDNA-derived constructs into the mouse genome. In the
      first construct, the APN cDNA was fused in 5' with the 1 kb upstream region of
      the APN gene and in 3' with the SV40 small intron and polyadenylation site. In
      the second construct, the 5' end of the APN cDNA was replaced by the
      corresponding domain of the APN gene comprising the three first introns, an
      additional intron (the rabbit beta-like globine intron 2) was inserted at the 3'
      extremity of the construct and the resulting DNA stretch was placed under the
      control of the rat intestinal fatty acid-binding protein (I-FABP) gene promoter.
      Transgenes were obtained with these two constructs, and RNA expression was
      evidenced by RT-PCR with the second construct in a transgene lineage. Using two
      different immunoassays, expression of the porcine APN protein was not detected in
      the transgenic intestines of animals of the RT-PCR positive lineage. Northern
      blot analyses did not revealed TGEV replication in infected adult mice.
      Additional assays will be carried out on young animals to detect potential TGEV
      susceptibility.

PMID- 9782263
TI  - Human biliary glycoproteins function as receptors for interspecies transfer of
      mouse hepatitis virus.
AB  - A variant Mouse Hepatitis virus (MHV), designated MHV-H2, was isolated by serial
      passage in mixed cultures of permissive DBT cells and nonpermissive Syrian
      Hamster Kidney (BHK) cells. MHV-H2 replicated efficiently in hamster, mouse,
      primate kidney (Vero, Cos 1, Cos 7), and human adenocarcinoma (HRT) cell lines
      but failed to replicate in porcine testicular (ST), feline kidney (CRFK), and
      canine kidney (MDCK) cells. To understand the molecular basis for coronavirus
      cross-species transfer into human cell lines, the replication of MHV-H2 was
      studied in hepatocellular carcinoma (HepG2) cells which expressed high levels of
      the human homologue of the normal murine receptor, biliary glycoprotein (Bgp).
      MHV-H2 replicated efficiently in human HepG2 cells, at low levels in breast
      carcinoma (MCF7) cells, and poorly, if at all, in human colon adenocarcinoma (LS
      174T) cell lines which expressed high levels of carcinoembryonic antigen (CEA).
      These data suggested that MHV-H2 may utilize the human Bgp homologue as a
      receptor for entry into HepG2 cells. To further study MHV-H2 receptor utilization
      in human cell lines, blockade experiments were performed with a panel of
      different monoclonal or polyclonal antiserum directed against the human CEA
      genes. Pretreatment of HepG2 cells with a polyclonal antiserum directed against
      all CEA family members, or with a monoclonal antibody, Kat4c (cd66abde), directed
      against Bgp1, CGM6, CGM1a, NCA and CEA, significantly reduced virus replication
      and the capacity of MHV-H2 to infect HepG2 cells. Using another panel of
      monoclonals with more restricted cross reactivities among the human CEA's, Col-4
      and Col-14, but not B6.2 B1.13, Col-1, Col-6 and Col-12 blocked MHV-H2 infection
      in HepG2 cells. These antibodies did not block sindbis virus (SB) replication in
      HepG2 cells, or block SB, MHV-A59 or MHV-H2 replication in DBT cells. Monoclonal
      antibodies Col-4, Col-14, and Kat4c (cd66abde) all reacted strongly with human
      Bgp and CEA, but displayed variable binding patterns with other CEA genes.
      Following expression of human Bgp in normally nonpermissive porcine testicular
      (ST) and feline kidney (CRFK) cells, the cells became susceptible to MHV-H2
      infection. These data suggested that phylogenetic homologues of virus receptors
      represent natural conduits for virus xenotropism and cross-species transfer.

PMID- 9782265
TI  - Molecular analysis of the coronavirus-receptor function of aminopeptidase N.
AB  - Aminopeptidase N (APN) is a major cell surface for coronaviruses of the serogroup
      I. By using chimeric APN proteins assembled from human, porcine and feline APN we
      have identified determinants which are critically involved in the coronavirus-APN
      interaction. Our results indicate that human coronavirus 229E (HCV 229E) is
      distinct from the other serogroup I coronaviruses in that determinants located
      within the N-terminal parts of the human and feline APN proteins mediate the
      infection of HCV 229E, whereas determinants located within the C-terminal parts
      of porcine, feline and canine APN mediate the infection of transmissible gastro
      enteritis virus (TGEV), feline infectious peritonitis virus (FIPV) and canine
      coronavirus (CCV), respectively. A further analysis of the mapped amino acid
      segments by site directed mutagenesis revealed that a short stretch of 8 amino
      acids in the hAPN protein plays a decisive role in mediating HCV 229E reception.

PMID- 9782266
TI  - Feline aminopeptidase N is a receptor for all group I coronaviruses.
AB  - Human coronavirus HCV-229E and porcine transmissible gastroenteritis virus
      (TGEV), both members of coronavirus group I, use aminopeptidase N (APN) as their
      cellular receptors. These viruses show marked species specificity in receptor
      utilization as they can only use APN of their respective species to initiate
      virus infection. Feline and canine coronaviruses are also group I coronaviruses.
      To determine whether feline APN could serve as a receptor for feline
      coronaviruses (FCoVs), we cloned the cDNA encoding feline APN (fAPN) by PCR from
      feline cells and stably expressed it in FCoV-resistant mouse or hamster cells.
      These became susceptible to infection with either of several biotypes of FCoVs.
      The expression of recombinant fAPN also made hamster and mouse cells susceptible
      to infection with other group I coronaviruses, including several canine
      coronavirus strains, transmissible gastroenteritis virus (TGEV), and human
      coronavirus HCV-229E. Thus, fAPN served as a functional receptor for each of
      these coronaviruses in group I. As expected, fAPN could not serve as a receptor
      for mouse hepatitis virus (MHV), a group II coronavirus which uses murine biliary
      glycoproteins as receptors. Thus, fAPN acts as a common receptor for
      coronaviruses in group I, in marked contrast to human and porcine APN
      glycoproteins which serve as receptors only for human and porcine coronaviruses,
      respectively. These observations suggest that cats could serve as a "mixing
      vessel" in which simultaneous infection with several group I coronaviruses could
      lead to recombination of viral genomes.

PMID- 9782267
TI  - Differential receptor-functionality of the two distinct receptor proteins for
      mouse hepatitis virus.
AB  - We compared the virus-binding activity and receptor-functionality of the receptor
      proteins isolated from mouse hepatitis virus (MHV)-susceptible BALB/c mice
      (MHVR1) and MHV-resistant SJL mice (MHVR2). By using a soluble receptor protein
      which lacked the transmembrane and intracytoplasmic domains, virus overlay
      protein blot assay and neutralization tests showed that MHVR1 bound to JHM cl-2
      virus with 300-500 times higher efficiency than to MHVR2. MHVR1 was revealed to
      have 10-30 fold higher receptor-functionality than MHVR2 when examined by
      measuring virus-binding to the receptor expressed on the cell surface. These
      findings suggested that the differences in susceptibility between BALB/c and SJL
      mice may depend upon the genotype of the MHV receptor.

PMID- 9782268
TI  - Porcine reproductive and respiratory syndrome virus infection of alveolar
      macrophages can be blocked by monoclonal antibodies against cell surface
      antigens.
AB  - PRRSV has a restricted macrophage tropism. To explore if the difference in
      susceptibility of porcine alveolar macrophages (PAM) and peripheral blood
      mononuclear cells (PBMC) to PRRSV is correlated with certain cellular surface
      antigens which may serve as a virus receptor, polyclonal antibodies against PAM
      and PBMC were prepared. Anti-PAM but not anti-PBMC antibodies protected PAM from
      PRRSV infection suggesting that specific receptor(s) may exist on PAM.
      Furthermore, monoclonal antibodies (MAbs) against putative receptor(s) were
      produced. Balb/c mice were firstly immune-tolerized with freshly isolated PBMC
      after which they were immunized with PAM. Two MAbs (41D3 and 41D5) which blocked
      PRRSV infection of PAM were obtained. MAb 41D3 and 41D5 prevented the attachment
      of purified PRRSV to PAM. Both MAbs bound to the cellular membrane of PAM but not
      to that of porcine peritoneal macrophages, PBMC and three porcine cell lines (SK,
      ST and PK-15) as revealed by flow cytometry. This membrane reactivity correlates
      well with the susceptibility of these cells to a PRRSV infection. Taken together,
      these data suggest that MAb 41D3 and 41D5 recognize a potential cellular receptor
      for PRRSV on PAM.

PMID- 9782269
TI  - Requirement of proteolytic cleavage of the murine coronavirus MHV-2 spike protein
      for fusion activity.
AB  - The spike (S) protein of a non-fusogenic murine coronavirus, MHV-2, was compared
      to that of a variant, MHV-2f, with fusion activity. Two amino acids differed
      between The S proteins of these viruses; one was located in the signal sequence
      (amino acid 12) and the other in the putative cleavage site (amino acid 757). To
      determine which one of these amino acid changes is important for the alteration
      of fusogenicity, chimeric S proteins between MHV-2 and -2f were constructed and
      expressed in DBT cells by a vaccinia virus expression system. The results
      revealed that one amino acid change (Ser to Arg) at position 757 is responsible
      for the acquisition of fusogenicity of the MHV-2f S protein. This change also
      altered the susceptibility to proteolytic cleavage of the MHV-2 S protein which
      was originally uncleavable. We concluded that the non-fusogenic activity of MHV-2
      results from the lack of cleavage of its S protein.

PMID- 9782270
TI  - The arterivirus replicase. The road from RNA to protein(s), and back again.

PMID- 9782271
TI  - Replication and transcription of HCV 229E replicons. p6.
AB  - Replicons based upon the human coronavirus 229E (HCV 229E) genome were
      transfected into HCV 229E infected cells. We demonstrate that a synthetic RNA
      comprised of 646 nucloetides from the 5' end and 1465 nucloetides from the 3' end
      of the HCV 229E genome is replication competent. We conclude that the cis-acting
      elements necessary for replication are located in these 5' and 3' genomic
      regions. Furthermore, we inserted the intergenic region of the HCV 229E
      nucleocapsid protein gene into this basic construct and were able to demonstrate
      the transcription of "subgenomic" RNAs.

PMID- 9782272
TI  - Substrate specificity of the human coronavirus 229E 3C-like proteinase.
AB  - Coronavirus gene expression involves proteolytic processing of the gene 1-encoded
      polyproteins and a key enzyme in this process is the virus-encoded 3C-like
      proteinase. In this study, we describe the biosynthesis of the human coronavirus
      229E 3C-like proteinase in Escherichia coli and the substrate specificity of the
      purified protein. Using immunofluorescence microscopy, we have also investigated
      the subcellular localization of the 3C-like proteinase and have found a punctate,
      perinuclear distribution of the proteinase in virus-infected cells.

PMID- 9782273
TI  - Processing of the MHV-A59 gene 1 polyprotein by the 3C-like proteinase.
AB  - The 3C-like proteinase of mouse hepatitis virus (MHV-3CLpro) is predicted to
      cleave at least 10 sites in the gene 1 polyprotein, resulting in processing of
      proteinase, polymerase and helicase proteins from the polyprotein. We have used
      E. coli expressed recombinant 3CLpro (r3CLpro) to define cleavage sites in
      carboxy-terminal region of the ORF 1a polyprotein. Polypeptides containing one or
      more putative 3CLpro cleavage site were translated in vitro from subcloned
      regions of gene 1, and the polypeptides were incubated with r3CLpro. Analysis of
      the cleavage products confirmed several putative cleavage sites, as well as
      identifying cleavage sites not previously predicted by analysis of the MHV
      sequence. Antibodies directed against a portion of the ORF 1a polyprotein were
      used to probe virus infected cells, and detected proteins that correspond to the
      cleavage sites used by 3CLpro in vitro. These results suggest that MHV 3CLpro
      cleaves at least 7 sites in the ORF 1a polyprotein, and that the specificity of
      3CLpro for cleavage site dipeptides may be broader than previously predicted.

PMID- 9782274
TI  - Expression, purification, and activity of recombinant MHV-A59 3CLpro.
AB  - The 3C-like proteinase (3CLpro) of MHV-A59 is predicted to mediate the majority
      of proteolytic processing events within the gene 1 polyprotein. We have
      overexpressed 3CLpro in E. coli as a fusion protein with maltose binding protein
      (MBP). The MBP-3CLpro fusion protein was purified from contaminating E. coli
      proteins by amylose column chromatography, and r3CLpro was cleaved from the
      fusion protein by factor Xa. Recombinant 3CLpro (r3CLpro) was able to cleave a
      polypeptide substrate containing mutated inactive 3CLpro and portions of the
      flanking domains. R3CLpro cleaved substrate completely within 5 minutes and the
      activity of r3CLpro was sensitive to inhibition by serine and cysteine proteinase
      inhibitors; however, it was not inhibited by EDTA, suggesting that metal ions
      were not critical for 3CLpro activity.

PMID- 9782275
TI  - Maturation of the polymerase polyprotein of the coronavirus MHV strain JHM
      involves a cascade of proteolytic processing events.
AB  - The RNA polymerase gene of the murine coronavirus mouse hepatitis virus (MHV)
      encodes a polyprotein of greater than 750 kDa. The amino-terminal cleavage
      product of the MHV polymerase polyprotein, p28, has been shown to be cleaved from
      the polyprotein by the virus-encoded protease PCP-1. We aim to identify the MHV
      JHM proteolytic products downstream of p28 and to determine which viral
      proteinase domains are responsible for generating each of them. To this end, we
      have generated antisera directed at specific MHV-JHM ORF1a regions and have used
      these antisera to identify six viral proteins, representing a large portion of
      ORF1a, from MHV-JHM-infected cells. These proteins include p28, p72, p65, p250,
      p210, and p27.

PMID- 9782276
TI  - Characterization of a papain-like cysteine-proteinase encoded by gene 1 of the
      human coronavirus HCV 229E.
AB  - Expression of the coronaviral gene 1 polyproteins, pp 1a and pp 1ab, involves a
      series of proteolytic events that are mediated by virus-encoded proteinases
      similar to cellular papain-like cysteine-proteinases and the 3C-like proteinases
      of picornaviruses. In this study, we have characterized, in vitro, the human
      coronavirus HCV 229E papain-like cysteine-proteinase PCP 1. We show that PCP 1 is
      able to mediate cleavage of an aminoterminal polypeptide, p9, from in vitro
      translation products representing the aminoproximal region of pp 1a/pp 1ab.
      Mutagenesis studies support the prediction of Cys1054 and His1278 as the
      catalytic amino acids of the HCV 229E PCP 1, since mutation of these residues
      abolishes the proteolytic activity of the enzyme.

PMID- 9782277
TI  - Proteolytic processing of the polyprotein encoded by ORF1b of the coronavirus
      infectious bronchitis virus (IBV).
AB  - We present here evidence demonstrating that four previously predicted Q-S(G)
      cleavage sites, encoded by the IBV sequences from nucleotide 15,129 to 15,134,
      16,929 to 16,934, 18,492 to 18,497, and 19,506 to 19,511, respectively, can be
      recognised and transcleaved by the 3C-like proteinase. Five mature products with
      sizes of approximately 100 kDa, 65 kDa, 63 kDa, 42 kDa and 35 kDa are released
      from the ORF1b polyprotein by the 3C-like proteinase-mediated cleavage at these
      positions. Meanwhile, expression of plasmids containing only the ORF1b region
      showed no autocleavage of the polyprotein encoded, suggesting that the 3C-like
      proteinase may be the sole proteinase involved in processing of the 1b
      polyprotein. These data may therefore represent a complete processing map of the
      polyprotein encoded by ORF1b of mRNA1.

PMID- 9782278
TI  - Further characterisation of the coronavirus IBV ORF 1a products encoded by the 3C
      like proteinase domain and the flanking regions.
AB  - Coronavirus IBV encodes a piconarvirus 3C-like proteinase. In a previous report,
      this proteinase was shown to undergo rapid degradation in vitro in reticulocyte
      lysate due to a posttranslational event involving ubiquitination of the protein.
      Several lines of evidence presented here indicate that the proteinase itself is
      stable. Translation of the IBV sequence from nucleotide 8864 to 9787 resulted in
      the synthesis of a 33 kDa protein, representing the full-length 3C-like
      proteinase. Pulse-chase and time-course experiments showed that this protein was
      stable in reticulocyte lysate for up to 2 hours. However, a 45 kDa protein
      encoded by the IBV sequence from nucleotide 8693 to 9911 underwent rapid
      degradation in reticulocyte lysate, but was stable in wheat germ extract,
      suggesting that an ATP-dependent protein degradation pathway may be involved in
      the turnover of the 45 kDa protein. To identify the IBV sequence responsible for
      the instability of this 45 kDa protein species, the region from nucleotide 8693
      to 9787 was translated both in vitro and in vivo, leading to the synthesis of a
      stable 43 kDa protein. These results suggest that a destabilising signal may be
      located in the IBV sequences between the nucleotides 9787 and 9911. Meanwhile,
      protein aggregation was observed when the product encoded by the IBV sequence
      from nucleotide 9911 to 10,510 was boiled for 5 minutes before being analysed in
      SDS-PAGE; when the same product was treated at 37 degrees C for 15 minutes,
      however, protein aggregation was not detected. Deletion studies indicate that the
      presence of a hydrophobic domain downstream of the 3C-like proteinase-encoding
      region may be the cause for the aggregation of the product encoded by this region
      of ORF 1a.

PMID- 9782279
TI  - Characterisation of a papain-like proteinase domain encoded by ORF1a of the
      coronavirus IBV and determination of the C-terminal cleavage site of an 87 kDa
      protein.
AB  - Our previous studies have shown that two overlapping papain-like proteinase
      domains (PLPDs) encoded by the IBV sequence from nucleotides 4155 to 5550 is
      responsible for cleavage of the ORF 1a polyprotein to an 87 kDa protein. In this
      study, we demonstrate that only the more 5' one of the two domains, PLPD-1
      encoded between nucleotides 4155 and 5031, is required for processing to the 87
      kDa protein. Site-directed mutagenesis studies have shown that the Cys1274 and
      His1435 residues are essential for the PLPD-1 activity, suggesting that they may
      be the components of the catalytic centre of this proteinase. Coexpression and
      immunoprecipitation studies have further revealed that PLPD can interact with the
      87 kDa protein. Meanwhile, data obtained from the construction and expression of
      a series of deletion mutants have indicated that the 87 kDa protein is encoded by
      the 5'-most 2600 bp part of ORF1a. further deletion and mutagenesis studies are
      underway to determine precisely the C-terminal cleavage site of the 87 kDa
      protein.

PMID- 9782280
TI  - Role of the nonstructural polyproteins in alphavirus RNA synthesis.

PMID- 9782281
TI  - An infectious cDNA clone of porcine reproductive and respiratory syndrome virus.
AB  - A plasmid containing a full-length cDNA copy of the Lelystad virus isolate (LV)
      of porcine reproductive and respiratory syndrome virus was constructed. When RNA
      that was transcribed in vitro from this full-length cDNA clone was transfected to
      BHK-21 cells, infectious LV was produced and secreted. The virus was rescued by
      passage to porcine alveolar lung macrophages or CL2621 cells. When infectious
      transcripts were transfected to porcine alveolar lung macrophages or CL2621 cells
      no infectious virus was produced due to the poor transfection efficiency of these
      cells. The growth properties of the viruses produced by BHK-21 cells transfected
      with infectious transcripts of LV cDNA resembled the growth properties of the
      parental virus from which the cDNA was derived. The infectious clone of LV
      enables us to mutagenize the viral genome at specific sites and thus will be
      useful for detailed molecular characterization of the virus, as well as for the
      development of a safe and effective live vaccine for use in pigs.

PMID- 9782283
TI  - A new model for coronavirus transcription.
AB  - Coronaviruses contain an unusually long (27-32,000 ribonucleotide) positive sense
      RNA genome that is polyadenylated at the 3' end and capped at the 5' end. In
      addition to the genome, infected cells contain subgenomic mRNAs that form a 3' co
      terminal nested set with the genome. In addition to their common 3' ends, the
      genome and the subgenomic mRNAs contain an identical 5' leader sequence. The
      transcription mechanism that coronaviruses use to produce subgenomic mRNA is not
      known and has been the subject of speculation since sequencing of the subgenomic
      mRNAs showed they must arise by discontinuous transcription. The current model
      called leader-primed transcription has subgenomic mRNAs transcribed directly from
      genome-length negative strands. It was based on the failure to find in
      coronavirus infected cells subgenome-length negative strands or replication
      intermediates containing subgenome-length negative strands. Clearly, these
      structures exist in infected cells and are transcriptionally active. We proposed
      a new model for coronavirus transcription which we called 3' discontinuous
      extension of negative strands. This model predicts that subgenome-length negative
      strands would be derived directly by transcription using the genome RNA as a
      template. The subgenome-length templates would contain the common 5' leader
      sequence and serve as templates for the production of subgenomic mRNAs. Our
      findings include showing that: 1. Replication intermediates (RIs) containing
      subgenome-length RNA exist in infected cells and are separable from RIs with
      genome-length templates. The RFs with subgenome-length templates are not derived
      by RNase treatment of RIs with genome-length templates. 2. The subgenome-length
      negative strands are formed early in infection when RIs are accumulating and the
      rate of viral RNA synthesis is increasing exponentially. 3. Subgenome-length
      negative strands contain at their 3' ends a complementary copy of the 72
      nucleotide leader RNA that is found in the genome only at their 5' end. 4. RIs
      with subgenomic templates serve immediately as templates for transcription of
      subgenomic mRNAs. Because subgenomic mRNAs are not replicated, i.e., copied into
      negative strands that in turn are used as templates for subgenomic mRNA
      synthesis, we propose that the subgenome-length negative strands must arise
      directly by transcription of the genome and acquire their common 3' anti-leader
      sequence after polymerase jumping from the intergenic regions to the leader
      sequence at the 5' end of the genome. This would make negative strand synthesis
      discontinuous and subgenomic mRNA synthesis continuous, which is the opposite of
      what was proposed in the leader primed model.

PMID- 9782282
TI  - The spike protein of transmissible gastroenteritis coronavirus controls the
      tropism of pseudorecombinant virions engineered using synthetic minigenomes.
AB  - The minimum sequence required for the replication and packaging of transmissible
      gastroenteritis virus (TGEV)-derived minigenomes has been determined. To this
      end, cDNAs encoding defective RNAs have been cloned and used to express
      heterologous spike proteins, to determine the influence of the peplomer protein
      in the control of TGEV tropism. A TGEV defective interfering RNA of 9.7 kb (DI-C)
      was isolated, and a cDNA complementary to DI-C RNA was cloned under the control
      of T7 promoter. In vitro transcribed DI-C RNA was replicated in trans upon
      transfection of helper virus-infected cells. A collection of DI-C deletion
      mutants (TGEV minigenomes) was generated and tested for their ability to be
      replicated and packaged. The size of the smallest minigenome replicated in trans
      was 3.3 kb. The rescue system was used to express the spike protein of an enteric
      TGEV isolate (C11) using as helper virus a TGEV strain (C8) that replicates very
      little in the gut. A mixture of two pseudorecombinant viruses containing either
      the helper virus genome or the minigenome was obtained. These pseudorecombinants
      display in the surface the S proteins from the enteric and the attenuated virus,
      and showed 10(4)-fold increase in their gut replication levels as compared to the
      helper isolate (C8). In addition, the pseudorecombinant virus increased its
      enteric pathogenicity as compared to the C8 isolate.

PMID- 9782284
TI  - Negative strand RNA synthesis by temperature-sensitive mutants of mouse hepatitis
      virus.
AB  - Mutants of the A59 strain of mouse hepatitis virus (MHV) were studied to
      determine the effects of temperature shift on negative and positive strand RNA
      synthesis. Mutant LA 9 was originally reported to have a selective temperature
      sensitive defect in negative strand synthesis. We found that this mutant
      continued to synthesize negative strands for at least one hour after temperature
      shift. LA 6 was found to possess a temperature sensitive defect in negative
      strand synthesis. Following temperature shift, negative strand synthesis rapidly
      declined. The effect of temperature shift on negative strand synthesis by LA 6
      was similar to the effect of cycloheximide treatment of the parental A59 virus.
      Temperature shift of Alb 16 infected cells did not stop negative strand synthesis
      but did prevent a corresponding rise in the rate of positive strand synthesis.
      Therefore, we suggest that Alb 16 is a conversion mutant because it cannot
      convert newly synthesized negative strands into templates for positive strand
      synthesis at the nonpermissive temperature.

PMID- 9782286
TI  - Cell proteins bind to a 67 nucleotide sequence within the 3' noncoding region
      (NCR) of simian hemorrhagic fever virus (SHFV) negative-strand RNA.
AB  - The 3'NCR of the SHFV negative-strand RNA [SHFV 3'(-)NCR RNA] is thought to be
      the initiation site of full-length and possibly also subgenomic positive-strand
      RNA and so is likely to contain cis-acting signals for viral RNA replication.
      Cellular and viral proteins may specifically interact with this region to form
      replication complexes. When in vitro transcribed SHFV 3'(-)NCR RNA was used as a
      probe in gel mobility shift assays, two RNA-protein complexes were detected with
      MA104 S100 cytoplasmic extracts. The specificity of thes RNA-protein interactions
      was demonstrated by competition gel mobility shift assays. Four MA104 protein
      (103, 86, 55, and 36 kDa) were detected by UV-induced cross-linking assays and
      three proteins (103, 55, and 36 kDa) were detected by northwestern blotting
      assays. The binding sites for these proteins were mapped to the region between
      nucleotides 117 to 184 on the SHFV 3'(-)NCR RNA. Four cellular proteins with
      identical molecular masses to those of the proteins that bind to the SHFV 3'(
      )NCR RNA were detected by the 3'(-)NCR of another arterivirus, LDV-C, suggesting
      that divergent arteriviruses utilize the same set of conserved cell protein
      domains.

PMID- 9782285
TI  - Cellular protein hnRNP-A1 interacts with the 3'-end and the intergenic sequence
      of mouse hepatitis virus negative-strand RNA to form a ribonucleoprotein complex.
AB  - We previously showed that several cellular proteins specifically bind to the 3'
      end and the intergenic sequences of the negative-strand RNA of mouse hepatitis
      virus (MHV), and proposed that these distant RNA sequences can be brought
      together by cellular and viral proteins (Furuya and Lai, 1993; Zhang et al.,
      1994; Zhang and Lai, 1995). The cellular protein p35 has been identified as a
      heterogeneous nuclear ribonucleoprotein (hnRNP) A1. We have now expressed hnRNP
      A1 as a glutathione-S-transferase (GST) fusion protein and demonstrated that the
      amino terminal two-thirds of hnRNP-A1 interacted with the two MHV regulatory RNA
      sequences (3'-end and intergenic sequences) through protein-RNA interaction while
      its carboxy-terminal glycine-rich domain mediated homomeric (protein-protein)
      interactions. In a partially reconstituted reaction, in which the two MHV RNA
      fragments and the purified GST-hnRNP-A1 fusion protein were mixed, an RNP complex
      was formed. Depletion of either hnRNP-A1 or one of the RNA components abolished
      the complex formation. These results indicate that hnRNP-A1 can mediate the
      formation of an MHV RNP complex, which includes both the negative-strand leader
      and intergenic sequences. Site-directed mutagenesis revealed that mutations in
      the MHV intergenic sequences, which inhibited MHV RNA transcription, also
      inhibited the RNP complex formation. Deletion analysis showed that the amino
      terminal RNA-binding domains of hnRNP-A1 is essential for the RNP complex
      formation while the carboxy-terminal protein-binding domain enhanced the complex
      formation by 90-fold. These findings provide direct evidence demonstrating that
      the negative-strand leader RNA and intergenic sequences can form an RNP complex
      mediated by cellular protein hnRNP-A1.

PMID- 9782287
TI  - Studies of murine coronavirus DI RNA replication from negative-strand
      transcripts.
AB  - The positive-strand transcripts as well as negative-strand transcripts of mouse
      hepatitis virus (MHV) defective interfering (DI) RNA, when introduced into MHV
      infected cells, resulted in DI RNA replication and accumulation. The leader
      sequence of the majority of DI RNAs that accumulated from the expression of
      negative-strand DI RNA transcripts with no extra non-MHV nucleotides at the 3'
      end switched to that of helper virus, whereas this leader sequence switching did
      not occur in most of the positive-strand DI RNAs that accumulated from the
      expressed negative-strand DI RNA transcripts with extra non-MHV nucleotides at
      the 3' end. These data demonstrated that the extra 4 nucleotides at the 3'-end of
      negative-strand DI RNA transcripts affected leader sequence switching on DI RNA,
      and indicated that the leader switching probably occurred during positive-strand
      DI RNA synthesis.

PMID- 9782288
TI  - The effect of deletion of a conserved 11 nucleotide sequence on mouse hepatitis
      virus RNA replication.
AB  - A conserved 11 nt sequence present at near the 3' end of mouse hepatitis virus
      (MHV) genomic RNA binds to host proteins and is important for MHV RNA replication
      (Yu and Leibowitz, 1995). To better understand the role of this 11 nt sequence in
      positive-strand MHV RNA replication, we examined whether positive-strand MHV DI
      RNAs from negative-strand DI RNA transcripts lacking the 11 nt sequence were
      synthesized in MHV-infected cells. Positive-strand DI RNAs did not accumulate
      efficiently, indicating that the conserved 11 nt sequence was necessary for
      positive-strand MHV RNA synthesis.

PMID- 9782289
TI  - Sequence elements involved in the rescue of IBV defective RNA CD-91.
AB  - Deletion mutagenesis has been used to identify essential regions for rescue of
      coronavirus defective RNAs (D-RNAs). Using this technique on a cloned IBV D-RNA
      CD-91, we have identified a region potentially important in its rescue. Comparing
      the sequence of D-RNAs rescued with those not rescued we have deduced that a 72
      base region corresponding to base number 13,824 to 13,896 in the viral genome is
      required for rescue. This may be an IBV D-RNA packaging signal or a cis-acting
      element involved in replication. Further experiments and modification of our
      techniques will be required to differentiate between the two processes.

PMID- 9782290
TI  - Rescue of IBV D-RNA by heterologous helper virus strains.
AB  - Coronavirus defective RNA (D-RNA) vectors could be developed to deliver selected
      genes for the production of recombinant coronavirus vaccines. An IBV D-RNA, CD
      61, derived from a naturally occurring IBV Beaudette D-RNA, CD-91, is being
      developed as a D-RNA vector for IBV. In order to use CD-61 as a vector it will
      require rescue by heterologous strains in addition to Beaudette. Rescue will be
      determined by recognition of replication and packaging signals within the D-RNA
      by the helper virus. The 5' and 3' UTRs are believed to contain sequences
      involved in replication and transcription. The 5' and 3' UTRs of six strains of
      IBV have been sequenced and experiments performed using six strains of helper
      virus for rescue of CD-61 to determine whether rescue correlates with sequence
      conservation within the 5' and 3' UTRs. Results indicate that all strains of
      helper virus rescued the D-RNA to varying degrees. Sequence comparisons show a
      high degree of sequence identity in the UTRs, but enough strain differences exist
      to be used as markers. The 5' and 3' UTRs of the D-RNAs rescued by the
      heterologous strains were also sequenced and leader switching between the helper
      virus and the Beaudette leader on the D-RNAs was observed.

PMID- 9782291
TI  - A strategy for the generation of infectious RNAs and autonomously replicating
      RNAs based on the HCV 229E genome.
AB  - A strategy to generate in vitro transcripts representing infectious RNAs and
      autonomously replicating RNAs based on the HCV 229E genome is presented. PCR-DNAs
      were ligated in vitro, resulting in 27 kbp and 22 kbp ligation products. These
      DNAs can now be transcribed in vitro and the RNAs tested for infectivity and
      their ability to replicate.

PMID- 9782292
TI  - Long distance RT-PCRs of human coronavirus 229E RNA.
AB  - The generation and cloning of cDNA fragments longer than 10 kb is often a
      difficult and time consuming task. In this study, we have analysed the conditions
      necessary of produce reverse transcripts longer than 10 kb that can be amplified
      by polymerase chain reaction. Thus, we isolated poly(A)-RNA from human
      coronavirus 229E infected MRC-5 cells and did reverse transcription using a
      sequence-specific primer. Subsequently, we amplified PCR products of varying
      length upstream of the primer position. Optimisation of the poly(A)-RNA
      preparation, the reverse transcription protocol and the polymerase chain reaction
      cycle conditions enabled us to successfully amplify regions of the human
      coronavirus 229E genome between 11.5 and 20.3 kb in length.

PMID- 9782293
TI  - Subgenomic RNA7 is transcribed with different leader-body junction sites in PRRSV
      (strain VR2332) infection of CL2621 cells.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV), like all members of
      the order Nidoviridae, is expressed in the infected cell as a nested set of
      subgenomic (sg) RNAs with a common 5'-leader sequence. We have determined that
      the 5'-leader sequence for the US prototype strain (VR2332, Collins, et al.,
      1992) is distinct from the European prototype strain [Lelystad (LV); Wensvoort,
      et al., 1991, Meulenberg et al., 1993a], yet these two strains use almost the
      same sequence for downstream sites of 5'-leader-body junction formation. Analysis
      of VR2332 genomic sequence identified several potential 5'-leader-body junction
      sequences upstream of open reading frame (ORF) 7, coding for the nucleocapsid
      protein, that could be used for generation of VR2332 sgRNA7 transcripts. Sequence
      determinations of RT-PCR-generated cDNA clones of sgRNA7 identified two species
      of RNA7 transcripts in infected cells, one utilizing a leader-body junction
      sequence (AUAACC) 123 nucleotides upstream of the AUG start site and one
      utilizing a sequence (UAAACC) 9 nucleotides upstream of the AUG start site for
      ORF7 translation.

PMID- 9782295
TI  - Construction of a mouse hepatitis virus recombinant expressing a foreign gene.
AB  - The genome of the coronavirus mouse hepatitis virus (MHV) contains genes which
      have been shown to be nonessential for viral replication and which could, in
      principle, be used as sites for the introduction of foreign sequences. We have
      inserted heterologous genetic material into gene 4 of MHV in order (i) to test
      the applicability of targeted RNA recombination for site-directed mutagenesis of
      the MHV genome upstream of the N gene; (ii) to develop further genetic tools for
      mutagenesis of structural genes other than N; and (iii) to examine the
      feasibility of using MHV as an expression vector. A DI-like donor RNA vector
      containing the MHV S gene and all genes distal to S was constructed. Initially, a
      derivative of this was used to insert a 19-nucleotide tag into the start of ORF
      4a of MHV-A59 using the N gene deletion mutant A1b4 as the recipient virus.
      Subsequently, the entire gene for the green fluorescent protein (GFP) was
      inserted in place of gene 4. This heterologous gene was shown to be expressed by
      recombinant viruses but not at levels sufficient to allow detection of
      fluorescence of viral plaques. Northern blot analysis of transcripts of GFP
      recombinants showed the expected displacement of the mobility, relative to those
      of wild-type, of all subgenomic mRNAs larger than mRNA5. An unexpected result of
      the Northern analysis was the observation that GFP recombinants also produced an
      RNA species the same size as that of wild-type mRNA4. RT-PCR analysis of the 5'
      end of this species revealed that it was actually a collection of mRNAs
      originating from a cluster of 10 different sites, none of which possessed a
      canonical intergenic sequence. The finding of these aberrant mRNAs, all of nearly
      the same size as wild-type mRNA4, suggests that long range structure of the MHV
      genome can sometimes be the sole determinant of the site of initiation of
      transcription.

PMID- 9782294
TI  - Organization of the simian hemorrhagic fever virus genome and identification of
      the sgRNA junction sequences.
AB  - SHFV is a member of the Arteriviridae family. Viruses within this family encode
      eight open reading frames (ORFs), two of which are translated from the full
      length genome RNA. The remaining six ORFs are translated from a nested set of six
      or seven 3' co-terminal, subgenomic RNAs (sgRNAs). We have cloned and sequenced
      approximately 6000 nucleotides (nt) from the 3' end of the SHFV genome. Eleven
      ORFs, numbered ORFs 1a, 1b, 2a, 2b, 3, 4, 5, 6, 7, 8, and 9, were identified,
      three more than the other arteriviruses. The characteristics of the peptides
      encoded by ORFs 2a through 9 were determined from their computer-generated amino
      acid sequences. We also amplified the junction sequences from each of the SHFV
      subgenomic RNAs (sgRNAs) using RT-PCR analysis. Eight separate junction sequences
      were found which suggests that SHFV produces eight sgRNAs during replication.
      ORFs 2a and 2b appear to be encoded on the same sgRNA implying that RNA 2 is
      polycistronic. Sequence analysis identified the conserved SHFV junction sequence
      as 5'-(U/C)(C/U)N(U/C)(U/C)(A/C/G)AC(C/U)-3'. Since SHFV encodes additional ORFs
      and produces additional sgRNAs during replication, these data suggest that SHFV
      may be more complex than the other arteriviruses.

PMID- 9782296
TI  - An essential secondary structure in the 3' untranslated region of the mouse
      hepatitis virus genome.
AB  - The 3' untranslated regions (3' UTRs) of coronaviruses contain the signals
      necessary for negative strand RNA synthesis and may also harbor elements
      essential for positive strand replication and subgenomic RNA transcription. The
      3' UTRs of mouse hepatitis virus (MHV) and bovine coronavirus (BCV) are more than
      30% divergent. In an effort to learn what parts of these regions might be
      functionally interchangeable, we attempted to replace the 3' UTR of MHV with its
      BCV counterpart by targeted RNA recombination. Initially, we tried to substitute
      the 3' 267 nucleotides (nt) of the 301 nt MHV 3' UTR with the corresponding
      region of the BCV 3' UTR. This exchange did not yield viable recombinant viruses,
      and the donor DI RNA was shown to be unable to replicate with MHV as a helper
      virus. Subsequent analysis revealed that the entire BCV 3' UTR could be inserted
      into the MHV genome in place of the entire MHV 3' UTR. It resulted that the
      failure of the initial attempted substitution was due to the inadvertent
      disruption of an essential conserved bulged stem-loop secondary structure in the
      MHV and BCV 3' URTs immediately downstream of the N gene stop codon.

PMID- 9782297
TI  - Regulation of mRNA 1 expression by the 5'-untranslated region (5'-UTR) of the
      coronavirus infectious bronchitis virus (IBV).
AB  - In this report, we show that expression of the coronavirus IBV mRNA1 is regulated
      by its 5'-UTR. Evidence presented demonstrates that the IBV sequence from
      nucleotide 1 to 1904 directs very inefficient synthesis of a product of
      approximately 43 kDa. Deletion of either the first 362 bp or the whole part of
      the 5'-UTR, however, dramatically increased the expression of the 43 kDa protein
      species. The mechanisms involved were investigated by two different approaches.
      Firstly, translation of the same construct in the presence of [3H]-leucine ruled
      out the possibility that initiation of small reading frames from non-AUG codons
      located in the 5'-UTR may compete with the authentic AUG initiation codon, and
      therefore inhibit the expression of ORF 1a. Secondly, expression and deletion
      analyses of a dicistronic construct showed that translation of the 43 kDa protein
      was initiated by ribosome internal entry mechanism. These studies suggest that a
      'weak' ribosome internal entry signal is located in the 5'-UTR and is involved in
      the regulation of mRNA1 expression.

PMID- 9782298
TI  - Mouse hepatitis virus nucleocapsid protein as a translational effector of viral
      mRNAs.
AB  - The mouse hepatitis virus (MHV) nucleocapsid protein stimulated translation of a
      chimeric reporter mRNA containing an intact MHV 5'-untranslated region and the
      chloramphenicol acetyltransferase (CAT) coding region. The nucleocapsid protein
      binds specifically the tandemly repeated-UCYAA- of the MHV leader. This RNA
      sequence is the same as the intergenic motif found in the genome RNA.
      Preferential translation of viral mRNA in MHV infected cells is stimulated in
      part by this interaction and represents a specific, positive translational
      control mechanism employed by coronaviruses.

PMID- 9782299
TI  - Progress towards the construction of a transmissible gastroenteritis coronavirus
      self-replicating RNA using a two-layer expression system.
AB  - Three transmissible gastroenteritis coronavirus (TGEV) defective interfering RNAs
      of 21, 10.6 and 9.7 kb (DI-A, DI-B and DI-C, respectively) were isolated.
      Dilution experiments showed that the largest DI RNA, DI-A, is a self-replicating
      RNA (replicon), and thus codes for a functional RNA polymerase and all the
      necessary replication signals. In order to engineer a cDNA encoding the RNA
      replicon a strategy based on the cloning of DI-C cDNA, followed by the insertion
      of the sequences required to complete the DI-A sequence has been developed. A
      cDNA complementary to DI-C RNA was cloned under the control of the CMV promoter
      (pDI-C-CMV) and rescued with a helper virus. In the ORF 1a of polymerase gene pDI
      C-CMV contained a 10 kb deletion and in ORF 1b a 1.1 kb deletion. The consensus
      sequence corresponding to the deleted regions was cloned, and the deletions in
      pDI-C-CMV were replaced to yield a complete cDNA clone of DI-A, pDI-A-21-CMV,
      containing a full-length TGEV polymerase, driven by a CMV promoter. Expression of
      a functional TGEV polymerase is being investigated.

PMID- 9782300
TI  - Molecular events in the assembly of retrovirus particles.
AB  - Retrovirus assembly results from the ability of a single gene product, the gag
      polyprotein precursor, to coalesce into a spherical particle capable of release
      from the cell. In conjunction with this primary process of capsid formation
      additional viral gene products such as the replicative enzymes and envelope
      glycoproteins as well as the genomic RNA are incorporated to form an infectious
      virus.

PMID- 9782301
TI  - Structure and intracellular assembly of the transmissible gastroenteritis
      coronavirus.
AB  - Coronaviruses have been described as pleomorphic, round particles with a helical
      nucleocapsid as the unique internal structure under the virion envelope. Our
      studies on the organization of the transmissible gastroenteritis coronavirus
      (TGEV) have shown that the structure of these viruses is more complex. Different
      electron microscopy techniques, including cryomicroscopy of vitrified viruses,
      revealed the existence of an internal core, most probably icosahedral, in TGEV
      virions. Disruption of these cores induced the release of elongated
      ribonucleoprotein complexes. Ultrastructural analysis of freeze-substituted TGEV
      infected swine testis (ST) cells showed characteristic intracellular budding
      profiles as well as two types of virions. While large virions with an electron
      dense internal periphery are seen at perinuclear regions, smaller viral particles
      exhibiting compact internal cores of poligonal contours are more abundant in
      areas closer to the plasma membrane of the cell. These data strongly suggest that
      maturation events following the budding process are responsible for the formation
      of the internal core shell, the new structural element that we have recently
      described in extracellular infectious TGEV virions.

PMID- 9782302
TI  - Characterization of coronavirus DI RNA packaging.
AB  - Studies of defective interfering (DI) RNAs of mouse hepatitis virus (MHV),
      suggest that a 69 nt-long packaging signal, which is located about 20 kb from the
      5'-end of the 31 kb-long MHV genomic RNA, is necessary and sufficient for MHV
      genomic RNA packaging into MHV particles. We demonstrated that use of a low pH
      culture medium combined with subsequent ultrafiltration increased MHV infectivity
      about 60 times over MHV preparations grown in neutral medium. Using this virus
      concentration procedure, we successfully prepared DI particle-rich MHV
      preparations. Characterization of virus samples released from the cells infected
      with DI particle-rich MHV revealed that infectious MHV genomic RNA was not
      required for packaging of DI RNAs. These data suggested that interaction of the
      DI packaging signal with an unidentified region(s) of helper virus genomic RNA is
      unlikely, and therefore unlikely to facilitate the packaging of MHV DI RNA into
      the MHV virion. Rather, both DI RNA and MHV genomic RNA probably use the
      packaging signal for RNA packaging.

PMID- 9782303
TI  - Coronavirus nucleocapsid protein. RNA interactions.
AB  - The coronavirus nucleocapsid protein (N) is involved in encapsidation and
      packaging of viral RNA. In this study we investigated the ability of the bovine
      coronavirus (BCV) N protein to interact with RNA. Histidine-tagged BCV N (his-N)
      protein was expressed in bacteria. A filter binding assay was established to
      quantitatively measure the binding efficiency of purified his-N to different
      RNAs. The results indicate that bacterially expressed N bound both BCV and mouse
      hepatitis coronavirus (MHV) RNAs. Binding to in vitro generated BCV and MHV RNA
      transcripts was significantly higher than binding to a non-coronavirus RNA.
      Similar binding efficiencies were measured for a BCV defective genome, pDrep, and
      a transcript that contained the MHV packaging signal. Interestingly, the entire
      MHV DI, pMIDI-C, was bound at a higher efficiency than the packaging signal
      alone. This is one of the first reports to show that N interacts with the MHV
      packaging signal.

PMID- 9782304
TI  - Coronavirus envelope glycoprotein assembly complexes.
AB  - Protein:protein interactions, and their subcellular localization, play important
      roles in coronavirus assembly. In this study, we have identified similar envelope
      glycoprotein complexes that are present in mouse hepatitis coronavirus A59 (MHV
      A59) and bovine coronavirus (BCV) infected cells. Complexes consisting of the
      spike (S) and membrane (M) proteins were identified in cells infected with MHV
      A59 or BCV. Kinetic analyses demonstrated that S and M quickly associated after
      translation, and suggested that both initially interacted in a pre-Golgi site. In
      addition, the hemagglutinin esterase (HE) was identified as part of a complex
      with M and S in BCV infected cells. Taken together, our data indicate that
      similar glycoprotein complexes are present in cells infected with two different
      coronaviruses, and thus likely represent important prerequisite complexes
      involved in virus assembly.

PMID- 9782305
TI  - Coronavirus envelope assembly is sensitive to changes in the terminal regions of
      the viral M protein.
AB  - Recently we demonstrated that the co-expressed coronavirus membrane proteins have
      the capacity to assemble viral envelopes which are similar to normal virus
      particles in dimensions and appearance, and which can form independent of a
      nucleocapsid (Vennema et al., 1996). For the formation of these particles only
      the M and the E protein are required; the S protein is dispensable but is
      incorporated when present. As we illustrate here, this virus-like particle
      assembly system is an ideal tool to study the interactions between the essential
      assembly partners M and E in molecular detail. Taking a mutagenetic approach we
      demonstrate that envelope assembly is critically sensitive to changes in the
      primary structure of both terminal domains of the M protein. The effects were
      most dramatically observed after mutation of the carboxy-terminal domain where
      the deletion of just one single amino acid at the extreme terminus abolished
      particle formation almost completely. But also some subtle mutations in the amino
      terminal domain were severely inhibitory to the assembly process. Interestingly,
      mutant M proteins that were themselves incompetent to support particle formation
      appeared to inhibit, in a concentration dependent manner, the assembly of
      particles by wild-type M and E protein.

PMID- 9782306
TI  - Interferon alpha inducing property of coronavirus particles and pseudoparticles.
AB  - Previous work in our laboratory have provided evidence that the membrane
      glycoprotein M of TGEV is centrally involved in efficient induction of alpha
      interferon (IFN-alpha) synthesis by non-immune peripheral blood mononuclear cells
      incubated with fixed, TGEV-infected cells or inactivated virions. Here we report
      recent completion of studies initiated to get a better understanding of the
      nature of the interferogenic determinant(s). Transfected cells expressing TGEV M
      together with the minor structural component E (formerly called sM) were found to
      trigger IFN-alpha synthesis. Co-expression of these two proteins was shown to be
      necessary and sufficient for assembly and release of pseudoparticles resembling
      TGEV virions. Purified pseudoparticles exhibited an interferogenic activity close
      to that of authentic virions. Chimeric recombinant particles expressing BCV M
      ectodomain also induced IFN. Examination of cell cultures infected by viruses
      representative of the three Nidovirales genera revealed that the capacity to act
      as an efficient IFN-alpha inducer is a common feature of viral particles of the
      coronavirus genus. Altogether these data bring new insights regarding the
      putative nature of the viral structure involved in IFN-alpha induction.

PMID- 9782308
TI  - Extracellular enveloped vaccinia virus. Entry, egress, and evasion.
AB  - Vaccinia virus is a large and complex virus that produces two types of infectious
      virus particles, termed intracellular mature virus (IMV) and extracellular
      enveloped virus (EEV). EEV contains an extra lipid envelope and ten associated
      proteins that are absent from IMV. Although EEV represents less than 1% of
      infectious progeny it is very important biologically. First, it mediates virus
      dissemination and second, it is the virus against which protective immune
      responses are directed. This article reviews the genes known to encode EEV
      proteins and their functions, describes recent data showing that the cellular
      receptors for IMV and EEV are different, and demonstrates that EEV, in contrast
      to IMV, is resistant to neutralisation by antibody.

PMID- 9782307
TI  - Expression and processing of nonstructural proteins of the human astroviruses.
AB  - The human astroviruses (HAst) are increasingly recognized as an important cause
      of gastroenteritis. These viruses contain a 6.8-kb positive-sense, single
      stranded RNA molecule that is infectious when transfected into permissive cells.
      The HAst gene 1 is composed of two open reading frames (ORFs 1a and 1b) connected
      by a ribosomal frameshift. Gene 1 is predicted to encode two nonstructural
      polyproteins (pp 1a and pp 1ab), and analysis of the HAst gene 1 sequence has
      resulted in predictions of a serine proteinase within the ORF1a polyprotein.
      However, none of the gene 1 proteins have been identified. To examine the
      expression and processing of the HAst2 gene 1 polyprotein, we have translated pp
      1a and pp 1ab in vitro. These ongoing studies will provide the foundation for
      correlating gene 1 expression in vitro with proteins expressed in virus-infected
      cells.

PMID- 9782310
TI  - Apoptosis of JHMV-specific CTL in the CNS in the absence of CD4+ T cells.
AB  - The role of CD4+ T cells in altering the activity of cytotoxic T lymphocytes
      (CTL) during infection of the central nervous system (CNS) by the neuroptropic
      JHMV strain of mouse hepatitis virus was examined. Adoptive transfer of in vitro
      activated CTL into CD4-depleted and control recipients showed that CTL were not
      effective in reducing JHMV replication within the CNS. The distribution of CD4+
      and CD8+ T cells within the CNS during JHMV infection showed that the CD4+ T
      cells remained in perivascular and subarachnoid spaces and few entered the
      parenchyma. By contrast approximately half of the CD8+ T cells entered the
      parenchyma. In CD4-depleted mice the trafficking of CD8+ T cells was not
      inhibited; however, the majority of the cells were found to be apoptotic. These
      data suggested that CD4+ T cells were not required for CTL induction but were
      required for the maintenance of CTL viability. The limited role of CD4+ T cells
      in CTL induction was confirmed by comparison of CTL activity from CD4-depleted
      and control mice.

PMID- 9782309
TI  - Resistance of naive mice to murine hepatitis virus strain 3 requires development
      of a Th1, but not a Th2, response, whereas pre-existing antibody partially
      protects against primary infection.
AB  - Murine hepatitis virus strain 3 (MHV-3) produces a host-strain-dependent spectrum
      of disease. The development of liver necrosis has been shown to be related to
      production of a unique macrophage procoagulant activity (PCA), encoded by the
      gene fgl-2, in susceptible mice. These studies were designed to examine the
      influence of Th1/Th2 cells on resistance/susceptibility and production of
      macrophage procoagulant activity (PCA) in resistant (A/J) and susceptible
      (Balb/cJ) strains of mice following infection with MHV-3. Immunization of A/J
      mice with MHV-3 induced a Th1 cellular immune response and one Th1 cell line
      (3F9.1) protected susceptible mice and inhibited production of PCA by macrophages
      both in vitro and in vivo. In contrast, immunization of Balb/cJ mice with an
      attenuated variant of MHV-3 derived from passaging MHV-3 in YAC-1 cells resulted
      in a Th2 response. Transfer of spleen cells and T cell lines from immunized
      Balb/cJ mice failed to protect naive susceptible syngeneic mice from infection
      with MHV-3 and augmented production of IL-1 beta, TNF-alpha and PCA by
      macrophages to MHV-3 in vitro. Serum from immunized Balb/cJ mice contained high
      titered neutralizing antibody which protected naive Balb/cJ animals from lethal
      primary MHV-3 infection. These results demonstrate that susceptible Balb/cJ mice
      generate a Th2 response following MHV-3 infection and that these Th2 cells
      neither inhibit MHV-3-induced macrophage PCA production nor protect naive mice
      from MHV-3 infection. The results suggest that antibody protects against primary
      infection, but could not eradicate ongoing infection. Ribavirin, a synthetic
      guanosine analogue prolonged survival to MHV-3 infection, inhibited production
      and transcription of the macrophage pro-inflammatory cytokines IL-1 beta and TNF
      alpha and Th2 cytokines while preserving Th1 cytokine production. Thus, this data
      defines the differential role of Th1/Th2 lymphocytes in primary and secondary MHV
      3 infection and further defines the importance of macrophage inflammatory
      mediators in the pathogenesis of MHV-3 infection.

PMID- 9782311
TI  - Mechanisms of viral clearance in perforin-deficient mice.
AB  - The roles of CD4+ T cells, IFN-gamma and TNF-alpha in viral clearance from the
      central nervous system (CNS) were examined in perforin gene deficient (PKO) mice.
      Depletion of CD4+ T cells from the PKO mice resulted in a significant 1 log10
      PFU/gm increase in viral titer over control-treated PKO mice. PKO mice treated
      with anti-IFN-gamma mAb also had a significant 1 log10 increase in infectious
      virus whereas inhibition of TNF-alpha did not alter viral clearance or clinical
      disease in the PKO mice. These data suggest, in addition to perforin-mediated
      cytolysis, CD4+ T cells and IFN-gamma, but not TNF-alpha could contribute to JHMV
      clearance from the CNS.

PMID- 9782313
TI  - MHV-induced fatal peritonitis in mice lacking IFN-gamma.
AB  - IFN-gamma gene was disrupted by homologous recombination in A3-1 embryonic stem
      cells. Germinally transmitted chimeric mice were successfully obtained and
      backcrossed with C57BL/6 (B6) mice 5 or 6 times. Deficiency of IFN-gamma in
      homozygous mice was confirmed by northern blot analysis of spleen cells
      stimulated with phorbor esther and calcium ionophore and also by IFN-gamma
      production in the culture supernatant of spleen cells stimulated with the same
      reagents. B6 mice lacking IFN-gamma were infected intraperitoneally (ip) with
      10(6) PFU of JHMV and monitored for their survival. Approximately 90% of the mice
      died at 50 days post-infection (pi) and the mean survival time was 28 days. Mice
      sacrificed at 3 weeks pi showed severe peritonitis accompanying the accumulation
      of a viscous fluid in the abdominal and thoracic cavities. Microscopically, the
      disease was characterized by disseminated granulomatous inflammation and
      exudative fibrinous serositis in the abdominal cavity. Infectious virus was
      isolated in most tissues including the liver, spleen, kidney, pancreas and lung
      during the experimental periods. The disease was not observed in wild-type or
      heterozygous littermates infected i.p. with JHMV. These results suggest that IFN
      gamma plays a critical role in MHV infection in mice. This experimental model may
      provide a unique opportunity to address the pathogenesis of virus-induced
      peritonitis such as feline infectious peritonitis in cats.

PMID- 9782312
TI  - Coronavirus infection and demyelination. Development of inflammatory lesions in
      Lewis rats.
AB  - Coronavirus infections of rodents can cause diseases of the central nervous
      system characterised by inflammatory demyelination. The lesions mimick in many
      aspects the pathology of multiple sclerosis in humans and of other neurological
      diseases. As an animal model for demyelination, we studied the MHV-JHM induced
      encephalomyelitis of Lewis rats. The pathomorphological analysis revealed
      patterns of lesions which developed in stages. Infected oligodendrocytes were
      first destroyed by necrosis. Later stages were characterized by demyelinated
      plaques. In the center of plaques, no virus antigen was found and
      oligodendrocytes were mainly destroyed by apoptosis. At the edge of plaques,
      virus antigen was expressed in parallel to infiltrations consisting of
      lymphocytes and macrophages. The prevailing mechanisms leading to demyelination
      may change individually and during defined stages of the disease. The
      transcriptional expression of chemoattractants and other mediators of
      inflammation was studied by semiquantitative RT-PCR. Virus induced inflammatory
      demyelination was accompanied by high expression of a relatively novel cytokine,
      the endothelial monocyte activating polypeptide II (EMAP II). By
      immunocytochemistry, EMAP II was detected in parenchymal microglia located both
      within the lesions and in unaffected areas. Furthermore, the level of
      transcriptional expression of the regulatory calcium binding S100 proteins MRP8,
      MRP14 and CP10 was associated with inflammatory demyelination and expression of
      IFN gamma, IL-2, TNF alpha, and iNOS.

PMID- 9782314
TI  - Coronavirus MHV-A59 causes upregulation of interferon-beta RNA in primary glial
      cell cultures.
AB  - Infection of mice with coronavirus mouse hepatitis virus strain MHV-A59 causes
      focal acute encephalitis, hepatitis and chronic demyelinating disease. To
      investigate host interferon (IFN) response to viral infection within the brain,
      RNA was extracted from A59-or MHV-2- infected and mock-infected primary astrocyte
      cultures from newborn mice, RT-PCR amplified RNA with primers specific for the
      various IFNs, transferred to nylon membranes and hybridized with IFN specific
      digoxigenin-labeled probes. Infection of primary astrocyte cultures from newborn
      mice with either A59 or MHV-2 caused upregulation of IFN-beta RNA, but not IFN
      gamma or IFN-alpha. Thus, brain astrocytes are capable of producing a local IFN
      beta response upon infection with MHV. The response of the other IFNs following
      MHV infection may be derived from inflammatory cells.

PMID- 9782315
TI  - Cytotoxic T lymphocyte responses to infectious bronchitis virus infection.
AB  - Cytotoxic T lymphocyte (CTL) activity to infectious bronchitis virus (IBV) was
      examined at regular intervals between 3 and 30 days post infection (p.i.). The
      maximal CTL lysis of target cells infected with IBV with 82% was detected at 10
      days p.i. The specific CTL activity began to decrease only after viral loads,
      which peaked at day 8 p.i. in both kidneys and lungs, started to decline.
      Therefore, the CTL response correlated with elimination of acute infection. IgM
      antibody did not appear until day 10 and levels peaked at day 12 p.i. whereas IgG
      antibody titers were detectable only by day 15 p.i., but continued to increase
      exponentially until day 30 p.i., the last day examined. IBV specific CTL
      epitope(s) were mapped within the carboxyl terminal 120 amino acids of
      nucleocapsid protein. In vivo inoculation of this fragment, as cDNA, induced
      protection against acute infection. The absence of viral neutralizing epitopes on
      the nucleocapsid protein would suggest that protection with known CTL eptiope(s)
      can be induced in the absence of neutralizing antibody.

PMID- 9782316
TI  - In vivo and in vitro interferon (IFN) studies with the porcine reproductive and
      respiratory syndrome virus (PRRSV).
AB  - Some of the interactions between the porcine reproductive and respiratory
      syndrome virus (PRRSV) and the porcine interferon-alpha (IFN-alpha) system were
      studied. In a first experiment, it was shown that pretreatment of primary porcine
      alveolar macrophages (AMs) with recombinant porcine (rPo) IFN-alpha 1 resulted in
      significant reductions of PRRSV yield and numbers of antigen expressing cells. In
      a second experiment, sensitivity of PRRSV to IFN-alpha was confirmed in vivo. In
      pigs inoculated with porcine respiratory coronavirus (PRCV)--a potent inducer of
      endogenous IFN-alpha in the lungs of pigs--followed 2 days later by PRRSV--lung
      PRRSV titers were 1.7 to 2.9 log10 TCID50 reduced compared to those in singly
      PRRSV inoculated pigs. It was concluded therefore that PRRSV has a fairly good
      sensitivity to the antiviral effects of IFN-alpha. A third experiment documented
      that in vivo PRRSV infection generally does not affect PRCV-induced IFN-alpha
      production in the lungs of pigs. In addition, it was shown that the IFN-inducing
      capacity of PRRSV is at least 159 times lower than that of PRCV. This finding
      suggests that cells other than AMs may be responsible for IFN production in the
      lungs of pigs.

PMID- 9782317
TI  - Identification of a common antigenic site in the nucleocapsid protein of European
      and North American isolates of porcine reproductive and respiratory syndrome
      virus.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) nucleocapsid (N)
      protein has been identified as the most immunodominant viral protein. The N
      protein genes from two PRRSV isolates Olot/91 (European) and Quebec 807/94 (North
      American) were cloned and expressed in Escherichia coli using the pET3x system.
      The antigenic structure of the PRRSV N protein was dissected using seven
      monoclonal antibodies (MAbs) and overlapping fragments of the protein expressed
      in E.coli. Three antigenic sites were found. Four MAbs recognized two
      discontinuous epitopes that were present in the partially folded protein or at
      least a large fragment comprising the first 78 residues, respectively. The other
      three MAbs revealed the presence of a common antigenic site localized in the
      central region of the protein (amino acids 50 to 66). This hydrophillic region is
      well conserved among different isolates of European and North American origin.
      However, since this epitope is not recognized by many pig sera, it is not
      adequate for diagnostic purposes. Moreover, none of the N protein fragments were
      able to mimic the antigenicity of the entire N protein.

PMID- 9782318
TI  - Intrahepatic alpha beta-TcRintermediate LFA-1high T cells are stimulated during
      mouse hepatitis viral infection.
AB  - Mouse hepatitis virus type 3 (MHV3), a coronavirus, is an excellent animal model
      for the study of thymic and extrathymic T cell subpopulation disorders induced
      during the viral hepatitis. To understand local hepatic immune responses, the
      phenotypes of resident hepatic lymphocytes were determined and compared that of
      splenic and thymic T cell subpopulations during the acute viral hepatitis induced
      by MHV3 in susceptible C57BL/6 mice. Single positive (SP) CD4+ or CD8+ cells
      strongly increased in the liver. A specific cell population, the double positive
      (CD4+ C8+) cells, normally present in liver and thymic cell preparations,
      decreased in C57BL/6 mice following the viral infection. alpha beta
      TcRintermediate T cells shifted toward alpha beta-TcRhigh T cells in the liver
      and thymus of infected mice, but not in their spleen. The specific alpha beta
      TcRint or high lymphocytes occurring in the liver of MHV3-infected mice expressed
      higher levels of leukocyte function antigen-1 (LFA-1) and Pgp-1 (CD44) activation
      markers, suggesting that they were either activated or antigen-experienced during
      the viral infection. No significant changes in T cell subpopulations were
      detected in the spleen. These observations suggest that MHV3 infection could
      induce an early in situ stimulation of resident hepatic T cells, despite a
      peripheral immunodeficiency in the thymus and spleen.

PMID- 9782320
TI  - A serological survey of human coronavirus in pigs of the Tohoku District of
      Japan.
AB  - A total of 2496 swine sera from 60 farms in the Tohoku District of Japan was
      examined for hemagglutination inhibiting (HI) antibodies to human coronavirus
      (HCV), swine hemagglutinating encephalomyelitis virus (HEV) and bovine
      coronavirus (BCV). HI antibodies to HCV OC43 strain and HEV 67N strain were
      highly prevalent with positivity rates of 91.4 and 82.1%, respectively, while the
      BCV Kakegawa strain was 44.2% positive. Farm D in Miyagi Prefecture showed the
      highest antibody titers to HCV OC43 strain with geometric mean titers (GMT) of
      1:200. These results suggest that pigs might be infected with HCV or an
      antigenetically related virus as well as HEV.

PMID- 9782319
TI  - Clonal deletion of some V beta+ T cells in peripheral lymphocytes from C57BL/6
      mice infected with MHV3.
AB  - Mouse hepatitis virus type 3 infection is generally accompanied by a severe
      immune dysfunction involving thymic or splenic T cell subpopulations. We
      postulate that the peripheral lymphoid cell depletions were caused by a selective
      deletion of some V beta subsets of mature T cells, as observed with
      superantigens. We have examined the expression of V beta 6, V beta 8 and V beta
      14 in T cell subpopulations from the spleen and lymph nodes of pathogenic L2-MHV3
      infected C57BL/6 mice. Cytofluorometric study showed decreases in splenic V beta
      8+, V beta 6+, and V beta 14+ T cell subpopulations at 72 hrs post-infection.
      Single positive CD4+ T cells were diminushed but not the CD8+ cells. In contrast,
      the various V beta splenic cell populations were not modified in mice infected
      with a non- pathogenic YAC-MHV3 variant. However, the V beta 8/CD4 ratio
      increased in splenic cells but decreased in lymphocytes from lymph nodes. The V
      beta 14/CD4 ratio decreased only in splenic cells while V beta 6/CD4 ratios were
      not modified. These results suggest that alterations in V beta cell populations
      may play a role in the L2-MHV3-induced immunodeficiency.

PMID- 9782321
TI  - A monoclonal antibody blocking ELISA for the detection of IBV antibodies in fowl.
AB  - A murine monoclonal antibody (mAb) reacting with the spike protein of seven field
      and laboratory strains of Infectious Bronchitis Virus (IBV) was characterised.
      Neutralisation tests performed in chicken tracheal organ culture showed that the
      mAb is directed against a conserved neutralising epitope. A monoclonal antibody
      blocking ELISA (B-ELISA) was developed based on the mAb. The sensitivity and
      specificity of the test was evaluated by examining sera and egg yolk from IBV
      free, vaccinated or naturally infected chickens from different European
      countries. The comparisons showed that the IBV blocking ELISA was very sensitive
      and more specific than the commercially available indirect ELISA and the
      haemagglutination-inhibition (HI) test. As part of the Swedish national health
      control program, more than 60,000 sera have been examined with the B-ELISA at the
      National Veterinary Institute (Sweden) since 1993. The test proved to be very
      specific in detecting the spread of disease during the Swedish IBV outbreaks in
      1994.

PMID- 9782322
TI  - Pathogenesis of coronavirus-induced infections. Review of pathological and
      immunological aspects.
AB  - Coronaviruses and arteriviruses infect multiple species of mammals, including
      humans, causing diseases that range from encephalitis to enteritis. Several of
      these viruses infect domestic animals and cause significant morbidity and
      mortality, leading to major economic losses. In this category are included such
      pathogens as transmissible gastroenteritis virus, porcine respiratory and
      reproductive virus and infectious bronchitis virus. The feline coronaviruses
      (FECV) generally do not cause infections with high morbidity but in a small
      percentage of cases, the virus mutates to become more virulent. This virus,
      feline infectious peritonitis virus (FIPV), causes severe disease in young cats.
      This disease is in large part immunopathological and understanding it is a major
      goal of coronavirus research.

PMID- 9782323
TI  - Role of CTL mutants in demyelination induced by mouse hepatitis virus, strain
      JHM.
AB  - Mouse hepatitis virus, strain JHM (MHV-JHM) is a well described cause of
      demyelination. C57B1/6 (B6) mice infected at the suckling stage in the presence
      of protective antibodies remain asymptomatic initially but later develop clinical
      disease (hindlimb paralysis). Infectious virus can be isolated from these mice.
      Recently, two MHV-specific target epitopes for cytotoxic CD8 T cells have been
      identified in B6 mice. Our results show that in all mice with hindlimb paralysis,
      mutations can be detected in the RNA encoding the immunodominant of the two
      epitopes. These mutations result in a loss of recognition by MHV-specific
      cytotoxic T cells. These changes are not detected, for the most part, in mice
      that remain asymptomatic nor in mice with acute encephalitis. These results
      suggest that the development of CTL escape mutants is necessary for hindlimb
      paralysis to develop in this model.

PMID- 9782324
TI  - Using a defective-interfering RNA system to express the HE protein of mouse
      hepatitis virus for studying viral pathogenesis.
AB  - We have developed a defective-interfering (DI) RNA of mouse hepatitis virus (MHV)
      as a vector for expressing a variety of cellular and viral genes including the
      chloramphenicol acetyltransferase (CAT), hemagglutinin' esterase (HE), and gamma
      interferon. Here, we used the HE-expressing DI RNA for examining the role of HE
      protein in viral pathogenesis. The pseudorecombinant virus containing an
      expressed HE protein was generated by infecting cells with MHV-A59, which does
      not express, HE, and transfecting the in vitro-transcribed DI RNA containing the
      HE gene. These pseudorecombinant viruses (DE-HE A59) were then inoculated
      intracerebrally into mice. Viruses recovered from cells infected with A59 and
      transfected with DI RNA expressing the CAT gene (DE-CAT A59) were used as a
      control. At various time points after inoculation, mice were observed for
      clinical symptoms. Tissues (brains and livers) were obtained for determining the
      replication of DI RNA by RT-PCR, virus replication by plaque assay, antigen
      expression by immunohistochemistry, and pathological changes. Results showed that
      all mice infected with DE-CAT A59 succumbed to infection by 9 days postinfection
      (d p.i). These data are identical to the pathogenesis of the parental A59 virus,
      demonstrating that inclusion of the DI RNA did not by itself alter pathogenesis.
      In contrast, only 40% of mice infected with DE-HE A59 succumbed to infection. The
      subgenomic mRNAs transcribed from the DI vector were detected at 1 and 2 d p.i.
      but not at subsequent time points, indicating that the genes in the DI vector
      were expressed only at an early stage of viral infection. No significant
      difference in virus replication in the brains was detected between these two
      groups of mice, suggesting that virus replication in brains was not affected by
      the expression of the HE. Histopathological examination showed only a small
      increase in the extent of inflammatory cell infiltration and reduced viral
      antigen in the mice infected with DE-HE A59. There was no difference in virus
      replication in the livers at 2 and 4 d p.i., but a 3 log10 reduction was detected
      in the livers of mice infected with DE-HE A59 at 6 d p.i. Histological
      examination showed a significant reduction in viral antigen, inflammation and
      necrosis in mice infected with DE-HE A59. These results indicate that the
      expression of HE from the DI vector altered the viral pathogenesis. This study
      thus demonstrates the usefulness of this system in studying the role of viral or
      cellular genes expressed locally at the sites of viral infection in viral
      pathogenesis.

PMID- 9782325
TI  - The mouse hepatitis virus A59 spike protein is not cleaved in primary hepatocyte
      and glial cell cultures.
AB  - Mouse hepatitis virus strain A59 (MHV-A59) produces mild meningoencephalitis and
      severe hepatitis during acute infection. To determine whether an in vitro system
      could be established which would mimic in vivo replication of the virus, we
      examined the ability of MHV-A59 to replicate in primary cultures of hepatocytes
      derived from C57BL/6 mice. Infection of hepatocytes with MHV-A59 resulted in low
      levels of replication, with virus remaining cell associated. Maximum viral yield
      was observed at 24 hours postinfection, while occasional syncytia were observed
      at 48 hours postinfection. Primary glial cell culture represents a potential in
      vitro system representing the second main target of MHV-A59, namely the brain. It
      is known that MHV-A59 produces a productive, but nonlytic infection in these
      cultures. Since cell-to-cell fusion is associated with the cleavage of S, the
      observation of little or no syncytia following MHV-A59 infection of both
      hepatocytes and glial cells prompted us to examine the cleavage of the spike
      protein (S) by Western blot analysis. The cleavage of S is inefficient in MHV-A59
      infected hepatocytes and in glial cells. Furthermore, no cleavage of this protein
      was detected in liver homogenates from C57BL/6 mice infected with MHV-A59. These
      data suggest that cleavage of the MHV-A59 S protein, and by inference cell-to
      cell fusion, does not seem to be essential for entry and spread of the virus in
      vivo and in vitro.

PMID- 9782326
TI  - The pathogenesis of MHV nucleocapsid gene chimeric viruses.
AB  - A set of viruses in which various segments of the nucleocapsid (N) gene of MHV
      have been substituted with the corresponding segments of bovine coronavirus (BCV)
      by targeted recombination were analyzed for their biologic properties. Histology
      for organ pathology and plaque assay for viral titer analysis following
      intracerebral (IC) inoculation were studied. One chimeric virus (Alb85), in which
      only a small segment of the N gene was replaced, exhibited a phenotype similar to
      wild type MHV-A59. However, three of the chimeric viruses (Alb106, Alb112 and
      Alb100) produced acute encephalitis and demyelination but without hepatitis
      following IC inoculation. Intravenous (IV) and intrahepatic (IH) inoculations
      were able to restore the ability of these viruses to produce hepatitis. The
      common denominator of the three chimeric viruses with a different phenotype is a
      region between aa 306 and aa 386 in which 17 amino acids (aa) differences exist
      between the two strains. Thus this region may contain determinants which enable
      the virus to exit the brain and reach the blood stream.

PMID- 9782327
TI  - Targeted recombination between MHV-2 and MHV-A59 to study neurotropic
      determinants of MHV.
AB  - MHV-A59 produces acute encephalitis, acute hepatitis and chronic demyelination in
      infected mice. MHV-2 produces only hepatitis and mild meningitis but without
      encephalitis or demyelination. We have previously studied a set of recombinant
      viruses between these two strains. The common denominator of viruses that
      produced encephalitis was a membrane (M) gene derived from MHV-A59. Thus to study
      the potential contribution of the M gene to acute encephalitis, chimeric viruses
      were produced in which the M gene of MHV-A59 was substituted with the M gene of
      MHV-2 by targeted recombination. A control virus was produced in which the M gene
      of A59 was recombined back into an A59 background. Viruses were then analyzed for
      their biologic properties and compared with the phenotypes of MHV-A59 and MHV-2
      by histopathology and plaque assays for viral titers in organs following
      intracerebral (IC) inoculation. All three chimeric viruses had a phenotype
      similar to MHV-A59. Thus, the replacement of the M gene of MHV-A59 with that of
      MHV-2 is insufficient to produce a phenotype that lacks encephalitis similar to
      MHV-2.

PMID- 9782329
TI  - Is the sialic acid binding activity of the S protein involved in the
      enteropathogenicity of transmissible gastroenteritis virus?
AB  - Transmissible gastroenteritis virus (TGEV) is able to recognize sialic acid on
      sialo-glycoconjugates. Analysis of mutants indicated that single point mutations
      in the S protein (around amino acids 145-155) of TGEV may result both in the loss
      of the sialic acid binding activity and in a drastic reduction of the
      enteropathogenicity. From this observation we conclude that the sialic acid
      binding activity is involved in the enteropathogenicity of TGEV. On the basis of
      our recent results we propose that binding of sialylated macromolecules to the
      virions surface may increase virus stability. This in turn would explain how TGEV
      as an enveloped virus can survive the gastrointestinal passage and cause
      intestinal infections.

PMID- 9782328
TI  - Mouse hepatitis virus receptor levels influence virus-induced cytopathology.
AB  - We developed human (HeLa) cell lines in which mouse hepatitis virus receptor
      (MHVR) levels could be regulated by addition of tetracycline. We used these cell
      lines to determine whether MHVR levels impact the degree of cytopathology induced
      by infection with the lytic MHV A59 strain. Two cultures were studied; HeLa
      MHVRlo (less than 3,000 molecules per cell) and HeLa-MHVRhi (300,000 molecules
      per cell). Both supported synthesis of infective A59 virus. However, the MHVRlo
      cells showed no virus-induced cytopathology while the MHVRhi cells uniformly died
      within 14 hours after infection. This cell death was not related to virus-induced
      syncytium formation as it occurred even in subconfluent cells overlaid with
      fusion-blocking antiviral antibodies. MHV A59 spike proteins produced by vaccinia
      vectors also killed the MHVRhi cells within 12 hours postinfection--MHVRlo cells
      infected in parallel were intact as judged by trypan blue exclusion. Our current
      hypothesis is that the accumulation of intracellular complexes composed of spike
      and MHVR proteins leads to acute single cell lysis.

PMID- 9782330
TI  - Isolation of hemagglutination-defective mutants for the analysis of the sialic
      acid binding activity of transmissible gastroenteritis virus.
AB  - The surface protein S of transmissible gastroenteritis virus (TGEV) has a sialic
      acid binding activity that enables the virus to agglutinate erythrocytes. A
      protocol is described that has been successfully applied to the isolation of
      hemgglutination-defective mutants. The potential of these mutants for the
      characterization of the sialic acid-binding site and the function of the binding
      activity is discussed.

PMID- 9782332
TI  - Persistent infection of neural cell lines by human coronaviruses.
AB  - Human coronaviruses (HCV) have been associated mainly with infections of the
      respiratory tract. Accumulating evidence from in vitro and in vivo observations
      is consistent with the neurotropism of these viruses in humans. To verify the
      possibility of a persistent infection within the central nervous system (CNS),
      various human cell lines of neural origin were tested for their ability to
      maintain chronic infection by both known strains of HCV, OC43 and 229E.
      Production of infectious progeny virions was monitored by an immunoperoxydase
      assay on a susceptible cell line and viral RNA was observed after RT-PCR.
      Astrocytic cell lines U-373 MG and U-87 MG did not sustain a persistent HCV-229E
      infection, even though they were susceptible to an acute infection by this virus.
      On the other hand, these two cell lines could maintain a persistent infection by
      HCV-OC43 for as many as 25 cell passages (about 130 days of culture). Relatively
      stable titers of infectious viral particles, as well as apparently constant
      amounts of viral RNA were detected throughout the persistent infection of U-87 MG
      cells. However, persistent infection of U-373 MG cells was accompanied by the
      detection of infectious viral particles from passage 0 to passage 13 and then
      from passage 20 to the end of the experiment. This gap in the production of
      infectious virions was correlated by a drop in the apparent amount of viral RNA
      detected at passages 15 and 20. These results confirm the ability of HCV-OC43 to
      persistently infect cells of an astrocytic lineage and, together with our
      previous observations of HCV infection of primary cultures of human astrocytes
      and the detection of HCV RNA in human brains, are consistent with the possibility
      that this human coronavirus could persist in the human CNS by targeting
      astrocytes.

PMID- 9782331
TI  - Role of mouse hepatitis virus-A59 receptor Bgp1a expression in virus-induced
      pathogenesis.
AB  - Expression of Bgp1a, a glycoprotein that serves as receptor for mouse hepatitis
      virus-A59 has been analyzed in various mouse tissues and correlated with the
      pathogenicity that this virus induces in the corresponding organs. Expression of
      Bgp1a was observed in many cells of epithelial origin, including hepatocytes and
      endothelial cells. It was also shown on macrophages and B lymphocytes. Bgp1a
      localization may easily explain infection and lysis of some cell types like
      hepatocytes. In contrast, other cell types that express the viral receptor are
      not infected after in vivo inoculation with mouse hepatitis virus-A59, which may
      be due to inaccessibility of the receptor to the virus during mouse infection, or
      to resistance to this virus in some cell types. This may account for the ability
      of the blood-brain barrier to prevent mouse hepatitis virus-A59 spreading into
      the central nervous system. In other organs, the virus may induce pathogenesis
      indirectly, resulting in the destruction of cells that do not express Bgp1a, like
      thymic lymphocytes, or else impair cell functions such as cytokine and
      immunoglobulin production by macrophages and B lymphocytes, respectively.

PMID- 9782333
TI  - Neuropathogenicity and susceptibility to immune response are interdependent
      properties of lactate dehydrogenase-elevating virus (LDV) and correlate with the
      number of N-linked polylactosaminoglycan chains on the ectodomain of the primary
      envelope glycoprotein.
AB  - We have developed differential RT-PCR methods to distinguish different isolates
      of LDV and have purified several quasispecies by repeated end point dilution in
      mice. They fall into two groups, each possessing two or more members. Group A
      viruses are non-neuropathogenic, highly resistant to in vitro neutralization by
      antibodies and efficient in establishment of a life-long, persistently viremic
      infection in mice despite a detectable immune response. Group B viruses, on the
      other hand, are neuropathogenic, much more sensitive to antibody neutralization
      and have an impaired ability to establish a high viremia persistent infection in
      immune competent mice. These properties seem to be interdependent and correlate
      with the number of N-glycosylation sites on the short (about 30 amino acid long)
      ectodomain of the primary envelope glycoprotein, VP-3P, which probably is part of
      the attachment site for the LDV receptor on permissive cells and harbors an
      epitope(s) reacting with neutralizing antibodies. Group A viruses possess three
      closely spaced N-linked polylactosaminoglycan chains, whereas group B viruses
      lack the two N-terminal ones. We postulate that lack of these
      polylactosaminoglycan chains endows group B viruses with the ability to interact
      with a receptor on anterior horn neurons resulting in neuropathogenesis. At the
      same time, it increases an interaction with neutralizing antibodies thus impeding
      the infection of macrophages newly generated during the persistent phase of
      infection which is essential for the continued rounds of replication of the
      virus.

PMID- 9782334
TI  - Arterivirus PRRSV. Experimental studies on the pathogenesis of respiratory
      disease.
AB  - Pigs were infected with the porcine respiratory and reproductive syndrome virus
      (PRRSV) by the oronasal route. We studied the development of histological
      lesions, sites of virus infection and of inflammatory infiltrates by quantitative
      evaluation of reactive cells. The animals developed a multifocal interstitial
      pneumonia. Clinical signs of pneumonia were observed from day 7 to 21. In the
      first stage, an acute alveolitis was found, which was characterised by a
      hyperplasia of type II pneumocytes within the septa and an accumulation of
      macrophages in the alveolar spaces. Within 2-4 days p.i., virus infected cells
      were prominent in lymphatic organs, but their number declined rapidly during the
      following days. In the following period, the number of virus antigen positive
      cells increased in the lung. An interesting discrepancy existed between the
      relatively small number of virus specific cells and the degree of intensive
      pneumonia. As a first step to analyse mechanisms leading to the induction of
      pneumonia, we studied transcriptional expression of cytokines and other
      immunomodulatory molecules by semiquantitative RT-PCR.

PMID- 9782335
TI  - Spread of swine hemagglutinating encephalomyelitis virus from peripheral nerves
      to the CNS.
AB  - Swine hemagglutinating encephalomyelitis virus (HEV) strain 67N was inoculated
      into the sciatic nerve or the right leg crural muscle of rats. In both cases, the
      virus was isolated first from the caudal half of the spinal cord on day 2 after
      inoculation, and from the rostral half of the spinal cord and the brain on day 3.
      The virus titers in the brain reached a maximum when the infected rats developed
      CNS symptoms on day 5. Using confocal laser scanning microscope, fluorescent
      positive cells were first found in the lumbar dorsal root ganglion (DRG) and
      spinal cord ipsilateral of the inoculated leg on day 3. Antigen positive neurons
      were found bilaterally in the lumbar DRG and spinal cord on day 4. On day 5
      specific fluorescence was observed in the neurons of the cerebral cortex,
      hippocampus, brainstem and Purkinje cells in the cerebellum.

PMID- 9782337
TI  - The pattern of induction of apoptosis during infection with MHV-3 correlates with
      strain variation in resistance and susceptibility to lethal hepatitis.
AB  - In the present study we have investigated the possibility that strain specific
      differences in the induction of apoptosis in macrophages could play a role in the
      resistance of strain A/J mice to MHV-3 induced hepatitis. MHV-3 infected
      macrophages from Balb/c and A/J mice were analyzed at various time points after
      infection. Apoptosis in A/J macrophages could be detected at 8 h post infection
      and increased significantly by 12 h, when almost 50-70% of the infected cells
      were undergoing apoptosis. In Balb/c macrophages, apoptotic changes were less
      pronounced and were observed in only 5-10% of the cells. MHV-3 induced apoptosis
      was inversely correlated with the ability of this virus to induce expression of
      fgl-2 prothrombinase protein and syncytia formation. Infected macrophages from
      A/J mice did not express fgl-2 protein and did not form syncytia. In contrast,
      infection of Balb/c derived macrophages resulted in fgl-2 expression and
      extensive syncytia formation. These data fit a model in which apoptosis of
      virally infected cells is a protective response which eliminates cells whose
      survival might be harmful for the whole organism.

PMID- 9782336
TI  - Expression of the fgl2 and its protein product (prothrombinase) in tissues during
      murine hepatitis virus strain-3 (MHV-3) infection.
AB  - Murine Hepatitis Virus Strain 3 (MHV-3) produces fulminant hepatitis with 80-90%
      mortality in Balb/cJ mice. Previous studies in our laboratory have shown that
      peritoneal macrophages from MHV-3 infected mice produce a procoagulant (PCA)
      which has the ability to cleave prothrombin to thrombin (prothrombinase) encoded
      by the gene fgl2 located on chromosome 5. PCA accounts for sinusoidal thrombosis
      and hepatic necrosis and the necrosis and mortality can be prevented by treatment
      of animals with a monoclonal antibody to PCA. These present studies were designed
      to examine the expression of this gene (mRNA by Northern analysis and in situ
      hybridization) and the gene product PCA (immunochemistry) in tissues recovered
      from MHV-3 infected Balb/cJ mice in an attempt to explain the liver specific
      nature of MHV-3 disease. Fgl2 gene expression was detected as early as 8 hours
      after MHV-3 infection which persisted to 48 hours in the liver, spleen and lungs
      whereas no gene expression was seen in the brain or kidneys despite the fact that
      equivalent viral titers were detected in all tissues at all times. In the liver,
      fgl2 gene expression was confined to endothelial and Kupffer cells with no
      expression in hepatocytes. Immunochemistry localized the PCA protein to Kupffer
      cells and endothelial cells and necrotic foci within the liver. No PCA protein
      was detected by immunochemistry in any other tissues at any time during the
      course of MHV-3 infection. These results explain the liver specific nature
      (fulminant hepatitis) of MHV-3 infection and provides further evidence for the
      role of PCA in the pathogenesis of fulminant hepatitis. MHV-3 induces selective
      transcription of the gene fgl2 and only hepatic reticuloendothelial cells produce
      functional protein (PCA) which is known to account for fulminant hepatic failure
      produced by MHV-3.

PMID- 9782338
TI  - The C12 mutant of MHV-A59 is very weakly demyelinating and has five amino acid
      substitutions restricted to the spike and replicase genes.
AB  - C12, an attenuated, fusion defective, very weakly hepatotropic mutant of MHV-A59
      has been further characterized. Analysis of C12 in vivo in C57BL/6 mice has shown
      that despite the fact that this virus replicates in the brain to titers at least
      as high as wild type and causes acute encephalitis similar to wild type, this
      virus causes minimal demyelination. Thus acute encephalitis is not sufficient for
      induction of demyelination by wild type MHV-A59. We have previously shown that
      C12 has two amino acid substitutions relative to wild type virus in the spike
      gene, Q159L (in the receptor binding domain of S1) and H716D (in the signal
      sequence for cleavage of S). We have now sequenced the rest of the 31 kb genome
      of C12 and compared it to wild type virus. Only three additional amino acids
      substitutions were found, all within the replicase gene, one in the predicted
      papain like proteinase (PLP)-2 domain and one in the predicted helicase domain.
      Thus, determinants of virulence, hepatotropism, and demyelination may map to the
      replicase gene as well as to the spike gene.

PMID- 9782339
TI  - Human macrophages are susceptible to coronavirus OC43.
AB  - Adherent adult and cord blood macrophages were infected with human coronavirus
      OC43 at a multiplicity of 1-1.5 and washed twice to remove unbound virus. Virus
      progeny was detected in the supernatant on day 1 and peaked at 2-3 days at an
      average titer of 5 +/- 3.9 x 10(6) pfu/ml from seven samples. Viral RNA was
      detected by nested set RT-PCR in infected macrophages incubated for 48 hr.
      Intracellular viral nucleocapsid was detected in 15% of the cells and surface
      staining for viral spike antigen was observed using monoclonal antibodies.
      Amplification of infectious virus and detection viral RNA and antigen synthesis
      in macrophages in vitro indicates susceptibility to OC43 virus.

PMID- 9782340
TI  - Transmissible gastroenteritis coronavirus carrier sow.
AB  - A sow infected with virulent transmissible gastroenteritis virus (TGEV) shed
      virulent virus in her feces for 18 months. The virus was isolated from rectal
      swabs beginning 2 days postexposure (PE) and continued at irregular intervals.
      Virus shedding was detected on 24 separate occasions. The titer of the virus shed
      ranged from < 1 x 10(2) pfu/ml to 7.2 x 10(3) pfu/ml, while the duration of the
      shedding ranged from 1 to 5 consecutive days. Inoculation of 3-day-old piglets
      with TGEV isolated from the sow proved the virus was virulent throughout the
      study. Virulent TGEV was isolated from the spleen, mesenteric lymph nodes, and
      the liver of the sow 544 days PE. This study demonstrates an apparently healthy
      sow can be a reservoir and shed virulent TGEV for an extended period of time.

PMID- 9782341
TI  - Equine viral arteritis. Current status in Finland.
AB  - A serological study for antibodies against equine arteritis virus (EAV) in
      Finland was performed during 1996. All equine sera delivered to the Virology Unit
      at the National Veterinary and Food Research Institute were tested with a micro
      neutralization test, using the Arvac strain as antigen. The study also included
      imported horses to evaluate EAV circulation in the countries of origin.
      Nucleocapsid gene sequences of 2 Finnish equine semen isolates were amplified
      with RT-PCR and sequenced. The genetic relationships of those isolates with
      strains isolated elsewhere in the world were analyzed. The Finnish isolates
      shared 98.2% nucleotide identity, and the closest relatives to the Finnish
      strains were isolated from the semen of 2 Norwegian horses in 1988 and 1989.

PMID- 9782342
TI  - Isolation and recombinant expression of an MHV-JHM neutralising monoclonal
      antibody.
AB  - The monoclonal antibody A1 (mab A1) efficiently neutralises the infection of
      susceptible cells by the murine hepatitis virus MHV-JHM in vitro and in vivo
      (Wege et al., 1984). The variable regions of mab A1 were amplified from mRNA of
      the respective hybridoma cell line by RT-PCR and integrated into different
      eukaryotic expression vectors. The biological function of the recombinant
      antibody constructs was verified by virus neutralisation assays. Whereas a
      complete recombinant antibody (mab A1rec.) expressed in transfected murine
      myeloma cells inhibited the MHV-JHM infection as well as the parental antibody, a
      single-chain Fv derived from mab A1 did not show any neutralising activity.

PMID- 9782343
TI  - Interference of coronavirus infection by expression of IgG or IgA virus
      neutralizing antibodies.
AB  - Mouse immunoglobulin gene fragments encoding the variable modules of the heavy
      (VH) and light (VL) chains of a transmissible gastroenteritis coronavirus (TGEV)
      neutralizing monoclonal antibody (MAb) have been cloned and sequenced. The
      selected MAb recognizes a highly conserved viral epitope and does not lead to the
      selection of neutralization escape mutants. Chimeric immunoglobulin genes with
      the variable modules from the murine MAb and constant modules of human gamma 1
      and kappa chains were constructed using RT-PCR. These chimeric immunoglobulins
      were stably or transiently expressed in murine myelomas and COS cells,
      respectively. The secreted recombinant antibodies had radioimmunoassay (RIA)
      titers higher than 10(3) and reduced the infectious virus more than 10(4)-fold.
      Recombinant dimeric IgA showed a 50-fold enhanced neutralization of TGEV relative
      to a recombinant monomeric IgG1 which contained the identical antigen binding
      site. Epithelial cell lines stably-transformed with these constructs and
      expressing either recombinant IgG or IgA TGEV neutralizing antibodies reduced
      virus production by > 10(5)-fold after infection with homologous virus, although
      a residual level of virus production (< 10(2) PFU/ml) remained in less than 0.1%
      of the cells.

PMID- 9782344
TI  - Lactogenic immunity in transgenic mice producing recombinant antibodies
      neutralizing coronavirus.
AB  - Protection against coronavirus infections can be provided by the oral
      administration of virus neutralizing antibodies. To provide lactogenic immunity,
      eighteen lines of transgenic mice secreting a recombinant IgG1 monoclonal
      antibody (rIgG1) and ten lines of transgenic mice secreting recombinant IgA
      monoclonal antibodies (rIgA) neutralizing transmissible gastroenteritis
      coronavirus (TGEV) into the milk were generated. Genes encoding the light and
      heavy chains of monoclonal antibody (MAb) 6A.C3 were expressed under the control
      of regulatory sequences derived from the mouse genomic DNA encoding the whey
      acidic protein (WAP) and beta-lactoglobulin (BLG), which are highly abundant milk
      proteins. The MAb 6A.C3 binds to a highly conserved epitope present in
      coronaviruses of several species. This MAb does not allow the selection of
      neutralization escaping virus mutants. The antibody was expressed in the milk of
      transgenic mice with titers of one million as determined by RIA, and neutralized
      TGEV infectivity by one million fold corresponding to immunoglobulin
      concentrations of 5 to 6 mg per ml. Matrix attachment regions (MAR) sequences
      were not essential for rIgG1 transgene expression, but co-microinjection of MAR
      and antibody genes led to a twenty to ten thousand-fold increase in the antibody
      titer in 50% of the rIgG1 transgenic animals generated. Co-microinjection of the
      genomic BLG gene with rIgA light and heavy chain genes led to the generation of
      transgenic mice carrying the three transgenes. The highest antibody titers were
      produced by transgenic mice that had integrated the antibody and BLG genes,
      although the number of transgenic animals generated does not allow a definitive
      conclusion on the enhancing effect of BLG co-integration. Antibody expression
      levels were transgene copy number independent and integration site dependent. The
      generation of transgenic animals producing virus neutralizing antibodies in the
      milk could be a general approach to provide protection against neonatal
      infections of the enteric tract.

PMID- 9782345
TI  - Utilising a defective IBV RNA for heterologous gene expression with potential
      prophylactic application.
AB  - Based on the natural ability of coronaviruses to undergo homologous RNA
      recombination, we are working to produce infectious bronchitis virus (IBV)
      recombinants using RNA generated from recombinant fowlpox viruses (FPV). The aim
      is to replace the spike (S) gene of an existing IBV vaccine strain with the S
      gene of a heterologous strain. CD-61 is an IBV defective RNA (D-RNA) derived from
      a naturally occurring IBV D-RNA (CD-91). CD-61 D-RNA is being investigated as an
      RNA vector for the expression of heterologous genes. T7-derived RNA transcripts
      of CD-61 can be replicated and passaged in the presence of helper virus,
      following electroporation into IBV-infected cells. CD-61 cDNA was modified by the
      addition of the hepatitis delta virus ribozyme plus T7 terminator downstream of
      the 3'UTR. This allowed the synthesis of discreet RNA transcripts. The complete
      cassette was cloned into an FPV transfer vector (pEFL10) for generating
      recombinant fowlpox viruses. FPV/CD-61 recombinants will be assessed for D-RNA
      production in IBV-infected cells. The luciferase reporter gene sequence has been
      inserted into the modified CD-61, under the control of the IBV transcription
      associated sequence (TAS) from gene 5. Luciferase has been successfully expressed
      from CD-61 in helper virus-infected cells.

PMID- 9782346
TI  - Intramuscular injection of plasmid DNA expressing mRNA7 coding the nucleocapsid
      protein of JHMV partially protected mice against acute infection with JHMV.
AB  - We constructed a plasmid expressing mRNA7 coding the nucleocapsid (N) protein of
      JHM strain of mouse hepatitis virus (JHMV) under the control of Rous sarcoma
      virus LTR, referred to as pRSV-mRNA7. When C57BL/6 mice injected intramuscularly
      (i.m.) with control plasmid DNA which contained no viral sequence were infected
      with JHMV, necrotic figures of neural cells and diffuse immersion of lymphatic
      cells in the pedunculus cerebri were observed. In the hypothalamus, vascular
      cuffing consisting of lymphatic cells was observed. In contrast, no histological
      change was observed throughout these areas of the brains in the JHMV-infected
      mice after injection with pRSV-mRNA7. These results showed that the injection
      with plasmid DNA expressing mRNA7 of JHMV partially protected mice against acute
      infection with JHMV in the brain. The plasmid DNA was i.m. injected into mice and
      the cytolytic activity of spleen cells from the mice was assessed by 51Cr-release
      assay. The spleen cells from the mice administrated with pRSV-mRNA7 showed a
      significant level of cytolytic activities against the transfected cells
      expressing the viral N protein even though the spleen cells were not cocultivated
      with stimulator cells. When the spleen cells from administrated mice with pRSV
      mRNA7 were cocultivated with stimulator cells, higher cytolytic activity was
      observed against the transfected cells, compared with the activity without
      stimulation.

PMID- 9782347
TI  - Inhibitory effects of modified oligonucleotides complementary to the leader RNA
      on the multiplication of mouse hepatitis virus.
AB  - Phosphorothioate oligonucleotides (PS-oligo) and PS-oligos with cholesterol
      conjugates (ChPS-oligo) complementary to the leader RNA of strain JHM of mouse
      hepatitis virus (JHMV) were more effective inhibitors of viral multiplication
      than natural oligodeoxynucleotides (PO-oligo) in JHMV-infected DBT cells. PS- and
      ChPS-oligos were 1,000 times more potent than unmodified PO-oligo. No significant
      difference was observed in the inhibitory efficiency between PS-oligo and ChPS
      oligo. Sequence-dependent inhibition of viral multiplication was shown at low
      concentrations (0.001-0.1 M) of antisense PS-oligo and ChPS-oligo.
      Phosphorothioate oligodeoxycytidine, PS-(dC)20, and PS-(dC)20 with cholesterol
      conjugates, and PS- and ChPS-oligo which have no significant homology to the JHMV
      sequences, showed inhibitory effects on JHMV multiplication at concentrations
      higher than 0.5 M. These results showed that PS-oligo and ChPS-oligo were more
      potent than PO-oligo in the inhibition of JHMV multiplication, and that PS-oligo
      and ChPS-oligo may inhibit JHMV multiplication by two different mechanisms, that
      is by sequence-dependent and sequence-independent manners.

PMID- 9782348
TI  - Adaptation and serial passage of bovine coronavirus in an established diploid
      swine testicular cell line and subsequent development of a modified live vaccine.
AB  - A virulent bovine coronavirus isolate (newborn calf diarrheal) was adapted and
      serially passaged in an established diploid swine testicular cell line (ST
      cells). The same cells have been used to produce modified live porcine rotavirus
      and coronavirus vaccines that are federally licensed and sold worldwide. Growth
      of the bovine coronavirus resulted in cytopathic effect characterized by cellular
      stranding and subsequent cell lysis. Virus yields were relatively high in the ST
      cells and active replication was confirmed by immune electron microscopy and
      immunofluorescence. Adaptation of bovine coronavirus to a diploid swine cell line
      has not been previously reported. Different cell culture passage levels of bovine
      coronavirus were evaluated by oral inoculation of clean-catch, colostrum-deprived
      calves. A passage level of bovine coronavirus was identified that multiplied in
      the calf without the clinical signs of disease associated with virulent passages.
      The modified live bovine coronavirus vaccine remained safe and efficacious even
      after 5-backpassages in calves. Further efficacy studies have shown that the
      modified live bovine coronavirus vaccine significantly protected calves from
      highly virulent challenges with either winter dysentery or newborn calf diarrheal
      coronavirus isolates.

PMID- 9782349
TI  - European serotype PRRSV vaccine protects against European serotype challenge
      whereas an American serotype vaccine does not.
AB  - Pigs were either vaccinated with an American serotype Porcine Reproductive and
      Respiratory Syndrome Virus (PRRSV) vaccine or with a European serotype vaccine. A
      control group of was left unvaccinated. At four weeks after vaccination the PRRSV
      specific antibody titres were determined and one third of each group was
      challenged with a Spanish, one third with a German and one third with a Dutch
      PRRSV wild type strain. The serological responses, measured at 4 weeks after
      vaccination, confirmed that both vaccines were of a different serotype. It was
      demonstrated that vaccination with an American serotype vaccine slightly reduced
      the amount of viraemia after challenge with European PRRSV wild type strains.
      Only after challenge with the Spanish PRRSV strain a moderate, and statistically
      significant, reduction in viraemia was observed. This is in contrast to
      vaccination with a European vaccine strain, where viraemia was completely
      suppressed after challenge with the German PRRSV isolate and almost completely
      suppressed after challenge with the Spanish and Dutch isolates.

PMID- 9782350
TI  - Population dynamics in the evolution of RNA viruses.
AB  - RNA virus quasispecies are subjected to processes of positive Darwinian
      selection, to a very active and continuous negative selection and to random
      genetic drift. The course of RNA virus evolution is often unpredictable, and
      recent results suggest that even highly conserved motifs, once regarded as
      essential for infectivity, may be rendered dispensable by singular evolutionary
      events. An immediate consequence of the quasispecies genetic organization of RNA
      viruses is a surprising ability to gain fitness once a minimal replication
      ability is established in a biological environment. The unique features of RNA
      genetics should not be underestimated since they are at the basis of the
      emergence of new viral diseases and of the current difficulties to control many
      diseases associated variable viruses.

PMID- 9782352
TI  - Selection in persistently infected murine cells of an MHV-A59 variant with
      extended host range.
AB  - Murine coronavirus MHV-A59 normally infects only murine cells in vitro and causes
      transmissible infection only in mice. In the 17 C1 1 line of murine cells, the
      receptor for MHV-A59 is MHVR, a biliary glycoprotein in the carcinoembryonic
      antigen (CEA) family of glycoproteins. We found that virus released from the
      600th passage of 17 C1 1 cells persistently infected with MHV-A59 (MHV/pi600)
      replicated in hamster (BHK-21) cells. The virus was passaged and plaque-purified
      in BHK-21 cells, yielding the MHV/BHK strain. Because murine cells persistently
      infected with MHV-A59 express a markedly reduced level of MHVR (Sawicki, et al.,
      1995), we tested whether virus with altered receptor interactions was selected in
      the persistently infected culture. Infection of 17 C1 1 cells by MHV-A59 can be
      blocked by treating the cells with anti-MHVR MAb-CC1, while infection by MHV/BHK
      was only partially blocked by MAb-CC1. MHV/BHK virus was also more resistant than
      wild-type MHV-A59 to neutralization by purified, recombinant, soluble MHVR
      glycoprotein (sMHVR). Cells in the persistently infected culture may also express
      reduced levels of and have altered interactions with some of the Bgp-related
      glycoproteins that can serve as alternative receptors for MHV-A59. Unlike the
      parental MHV-A59 which only infects murine cells, MHV/BHK virus was able to
      infect cell lines derived from mice, hamsters, rats, cats, cows, monkeys and
      humans. However, MHV/BHK was not able to infect all mammalian species, because a
      pig (ST) cell line and a dog cell line (MDCK I) were not susceptible to
      infection. MHV/pi600 and MHV/BHK replicated in murine cells more slowly than MHV
      A59 and formed smaller plaques. Thus, in the persistently infected murine cells
      which expressed a markedly reduced level of MHVR, virus variants were selected
      that have altered interactions with MHVR and an extended host range. In vivo, in
      mice infected with coronavirus, virus variants with altered receptor recognition
      and extended host range might be selected in tissues that have low levels of
      receptors. Depending upon the tissue in which such a virus variant was selected,
      it might be shed from the infected animal or eaten by a predator, thus presenting
      a possible means for initiating the transition of a variant virus into a new host
      as a model for an emerging virus disease.

PMID- 9782351
TI  - Does IBV change slowly despite the capacity of the spike protein to vary greatly?
AB  - We have sequenced that part of the spike protein (S) gene which encodes the
      aminoterminal and most variable quarter (hypervariable region, HVR) of the S1
      subunit of 28 isolates of the 793/B (also known as CR88 and 4/91) serotype of
      infectious bronchitis virus (IBV) and the whole of S1 for nine of them. The
      isolates were from France and Britain between the years 1985 (first isolation)
      and 1996. The maximum nucleotide and amino acid differences between the first
      isolate and the others were 4.1% and 7.6%, respectively, for the whole of S1 and
      7.1% and 14.6%, respectively, in the HVR. Analysis within clearly recognisable
      subgroups suggested that even in the HVR the nucleotide mutation rate was only
      0.3 to 0.6% per year. However, there was no evidence that mutations had become
      fixed in a progressive manner; this serotype did not appear to be evolving.
      Strains isolated several years apart could be more similar than those isolated in
      a given year. It is likely that the amino acid changes are largely at positions
      where amino acid differences are tolerated rather than as a consequence of immune
      pressure. Reasons for this conclusion are discussed.

PMID- 9782353
TI  - Receptor homologue scanning functions in the maintenance of MHV-A59 persistence
      in vitro.
AB  - Cell lines and viruses were isolated from mouse hepatitis virus (MHV-A59)
      persistently-infected DBT cells at different times postinfection. Cloned cell
      lines had cured virus infection, displayed low levels of MHVR receptor expression
      and were progressively more resistance to MHV infection. MHV persistence was
      likely maintained by epigenetic expression of the MHVR receptor in subsets of
      these resistant cells and by the emergence of persistent viruses characterized by
      high affinity MHVR receptor usage. Persistent viruses also displayed higher
      affinity for alternative biliary glycoprotein receptors suggesting that receptor
      homologue scanning functioned in the maintenance of persistence. Importantly,
      persistent viruses isolated after 210 days postinfection efficiently replicated
      in human HepG2 cells, a hepatocarcinoma cell line, suggesting that persistence
      promotes the interspecies transfer of MHV.

PMID- 9782354
TI  - Viral evolution and CTL epitope stability during JHMV infection in the central
      nervous system.
AB  - The JHM strain of mouse hepatitis virus (JHMV) establishes a persistent infection
      in the murine central nervous system (CNS) associated with chronic ongoing
      demyelination in the absence of detectable virus. To distinguish between immune
      and replication associated mechanisms of persistence, brains from acutely and
      persistently infected mice were analyzed for viral RNA mutations in the
      encapsidation sequence (ECS) and regions encoding either the transmembrane
      domains of the matrix (M) protein or a protective CTL epitope in the nucleocapsid
      (N) protein. Detection of the ECS to 120 days post infection (p.i.) indicated low
      levels of replication. The ECS remained stable whereas the fragment encoding the
      CTL epitope revealed extensive diversity with mutation frequencies in the order
      of 2.0 per 1000 nts. The M gene also remained stable despite random mutations
      during the acute phase. Mutations in the N gene were random and not selected for
      during persistence, with the exception of a single prominent Pro363 to Ser
      substitution in a region not associated with any known regulatory function or
      immune response. Mutations within the CTL epitope affecting CTL recognition were
      found early in responder BALB/c mice (H-2d), but also in non-responder C57BL/6 (H
      2b) mice, suggesting that CTL escape variants play no significant role in
      establishing persistence.

PMID- 9782355
TI  - Quasispecies development by high frequency RNA recombination during MHV
      persistence.
AB  - Recent studies suggest that infectious viruses and particularly persisting viral
      RNAs often exist as diverse populations or "quasispecies". We have developed an
      approach to characterize populations of the murine coronavirus mouse hepatitis
      virus (MHV) generated during persistent infection which has allowed us to begin
      to address the role of the viral quasispecies in MHV pathogenesis. We analyzed
      the population of persisting viral RNAs using reverse-transcription polymerase
      chain reaction amplification (RT-PCR) of the S1 "hypervariable" region of the
      spike gene followed by differential colony hybridization to identify spike
      deletion variants (SDVs) from acute and persistently infected mice. Sequence
      analysis revealed that mice with the most severe chronic paralysis harbored the
      most complex quasispecies. Mapping of the SDVs to the predicted RNA secondary
      structure of the spike RNA revealed that an isolated stem loop structure is
      frequently deleted. Overall, these results are consistent with high frequency
      recombination at sites of RNA secondary structure contributing to expansion of
      the viral quasispecies and persisting viral pathogenesis.

PMID- 9782356
TI  - Coronavirus infection and demyelination. Sequence conservation of the S-gene
      during persistent infection of Lewis-rats.
AB  - Coronaviruses display a large phenotypic variability, which may be an important
      factor for diversification and selection. Previous studies have demonstrated that
      the S-protein is an essential determinant of virulence and pathogenicity.
      Therefore we studied the S-gene as an indicator molecule for selection processes
      employing two different MHV-JHM variants. First, Lewis-rats were infected with
      MHV-JHM-Pi, a variant that causes demyelinating disease after several weeks p.i.
      It was not possible to isolate infectious MHV-JHM-Pi from such rats, although
      viral proteins were expressed. The S-gene was rescued directly from brain tissue
      employing RT-PCR technology. The amplicons were sequenced in bulk or at the level
      of single clones. We detected no evidence for an increase of S-gene mutants
      during the length of time. Only few mutations were found at the clonal level. The
      changes were distributed throughout the analysed S-gene fragments without a
      predilection in their location. The frequency of mutation remained low within a
      range of 0.03 to 0.5 mutations per thousand nucleotides. As a second approach, we
      sequenced the S-genes of viruses isolated from brain tissue infected with MHV-JHM
      ts43. Infection of adult Lewis rats with that mutant resulted several weeks to
      months p.i. in demyelinating encephalomyelitis. The S-gene of this virus contains
      an insertion of 423 bp in the S1 region, which is identical to a polymorphic
      region described for MHV-4. In contrast to JHM-Pi, infectious MHV-JHM-ts43 was
      readily to isolate from brain tissue. The S-gene sequences of virus isolated 45
      106 days p.i. from diseased rats were identical with that of the input virus.
      These results show, that during a persistent infection of Lewis-rats the S-gene
      was highly conserved.

PMID- 9782357
TI  - Prokaryotic expression of porcine epidemic diarrhoea virus ORF3.
AB  - Wild type (wt) and cell culture adapted (ca) strains of the coronavirus PEDV
      differ in their ability to cause diarrhea in neonate piglets: the wt strains are
      virulent; the ca strains are attenuated. Comparison of the available nucleotide
      sequences obtained from the different viral isolates revealed almost complete
      sequence identity with the exception of variations and truncations in open
      reading frame 3 (ORF3) observed exclusively in ca-PEDV isolates. In order to
      study the biological function(s) of the putative ORF3 product, the molecule was
      expressed as a heterodimeric fusion protein in E. coli. ORF3 was fused in frame
      to the alkaline phosphatase gene. Simultaneously, the construct was designed to
      form specific heterodimers by inclusion of the well known leucine zipper motiv of
      Jun and Fos. The heterodimerization partner contained the E. coli heat-labile
      enterotoxin subunit B (LTB) to allow specific binding to the eukaryotic cell
      receptor GM1. Our results indicate that heterodimeric fusion protein containing a
      truncated form of ORF3 was produced in high amounts, carried the expected ORF3
      epitope, showed phosphatase activity, and was able to bind to the GM1 receptor.
      In contrast, a fusion protein containing the entire sequence of the ORF3 product
      was produced in minute amounts, indicating that it may have biological activity
      in prokaryotes, which led to the reduction of the amounts of proteins expressed.

PMID- 9782358
TI  - Further analysis of the genome of porcine epidemic diarrhoea virus.
AB  - We report here the continued determination and analysis of the nucleotide
      sequence of both wild type (wt) and cell culture adapted (ca) porcine epidemic
      diarrhoea coronavirus (PEDV). These studies were undertaken with two objectives
      in mind: the identification of common and divergent features in the genomic
      sequences of wt and ca PEDV which can explain the differences in virulence of
      these isolates and the further exploration of the relationship of PEDV to other
      coronaviruses.

PMID- 9782359
TI  - Genetic variation in the PRRS virus.
AB  - Porcine reproductive and respiratory syndrome (PRRS) is characterized by late
      term abortions and stillbirths in sows and respiratory difficulties in nursery
      pigs. The disease appeared in Europe and North America at approximately the same
      time between 1985 and 1990. The PRRS virus was isolated shortly thereafter and
      demonstrated unexpectedly profound differences between European (Lelystad) and
      North American (VR2332) isolates as measured by serological crossreactivity and
      nucleotide sequence similarity. In order to determine the amount of genetic
      variation in the PRRS virus and to understand the molecular mechanisms of viral
      evolution, nucleotide sequences of PRRS virus strains were determined.
      Comparisons among ten U.S. strains showed that variation in primary nucleotide
      sequence between isolates ranged from 2.5% to 7.9% for ORFs 2-7. In contrast,
      Lelystad virus was, on average, 35% different from US clones. These results
      provided direct molecular evidence that US and European PRRSV isolates
      represented genetically distinct groups of the same viral family. A further
      analysis of more than 150 isolates in the United States and Canada demonstrated
      that the PRRS virus in North America represents a single large and diverse
      genetic group that is distinct from European forms of the virus.

PMID- 9782361
TI  - Comparison of the di- and trinucleotide frequencies from the genomes of nine
      different coronaviruses.
AB  - As an alternative to protein alignments for the comparison of sequences, the
      reiterations of mono- di- and trinucleotide frequencies were used for the
      comparison of coronavirus sequences. The relative abundance of the di- and
      trinucleotide frequencies within the 3' part from nine coronavirus genomes were
      determined. The patterns of dinucleotide frequencies and the trinucleotide
      frequencies showed some common features for all coronaviruses but also
      differences between the groups formerly defined on the base of antigenic
      relatedness. The normalised dinucleotide frequencies were further used to
      calculate the distances between coronavirus sequences. Based on the dinucleotide
      frequency distances, coronaviruses can be divided into two groups which roughly
      reflect the taxonomic groups. In this kind of evaluation, however, IBV occupies a
      position different to the one that it would take based on most protein sequence
      comparisons. Based on similarities within coding sequences and antigenic
      properties IBV occupies a place outside of both groups. Based on the dinucleotide
      frequencies IBV gained a position in between of the TGEV-related and the MHV
      clustered coronaviruses.

PMID- 9782360
TI  - Sequence analysis of the nucleocapsid protein gene of the porcine reproductive
      and respiratory syndrome virus Taiwan MD-001 strain.
AB  - The 3'-portion of the genome from a Taiwan isolate of porcine reproductive and
      respiratory syndrome (PRRS) virus, strain MD-001, was cloned and sequenced. The
      resultant 549 nucleotides contained an open reading frame with a coding capacity
      of 123 amino acids (predicted Mr 13,600). The predicted protein corresponds to
      the nucleocapsid protein, the gene product of ORF7. Comparative sequence analysis
      of several known PRRSV strains indicated that this protein showed the highest
      degree of amino acid similarity to the US VR2332 and the Canadian IAF-Exp91
      strains (92.7%) and the least to the Dutch Lelystad strain (56.5%). The
      phylogenic trees constructed on the basis of the known PRRSV nucleotide sequences
      indicated that MD-001 strain belongs to the North American strain cluster and
      that it is distinct from the European virus.

PMID- 9782362
TI  - Sequence determination and genetic analysis of the leader region of various
      equine arteritis virus isolates.
AB  - The entire leader sequence of ten equine arteritis virus (EAV) isolates including
      the Bucyrus reference strain was determined and analyzed at the primary
      nucleotide and secondary structure levels. The leader sequence of eight EAV
      isolates was determined to be 206 nucleotides (nt) in length, whereas those of
      the 86AB-A1 and 86NY-A1 isolates were found to be 205 and 207 nt in length,
      respectively. The sequence identity of the leader sequences between the different
      isolates and the Bucyrus reference strain ranged from 94.2 to 98.5%. An AUG start
      codon found at position 14 in all EAV isolates could initiate an open reading
      frame (ORF) that could produce a polypeptide of 37 amino acids, except for the
      86NY-A1 isolate where the intraleader polypeptide would contain 54 amino acids.
      Five patterns of computer-predicted RNA secondary structures were identified in
      the ten EAV leader regions analyzed. All EAV isolates showed three conserved stem
      loops (designated A, B and C). An additional conserved stem-loop (D) was observed
      in six EAV isolates, including the Bucyrus reference strain. Based on the
      presence or absence of stem-loop D, all EAV isolates analyzed in this study could
      be tentatively classified into two genogroups (I and II). The significance of the
      intraleader ORF and the predicted secondary structures has yet to be determined.

PMID- 9782363
TI  - Genetic variation and phylogenetic analysis of open reading frames 3 and 4 of
      various equine arteritis virus isolates.
AB  - The genetic variation in equine arteritis virus (EAV) nonstructural (NS) protein
      encoding open reading frames (ORF) 3 and 4 genes was investigated. Nucleotide and
      deduced amino acid sequences from seven different EAV isolates (one European, one
      American and five Canadian isolates) and the Arvac vaccine strain were compared
      with those of the Bucyrus reference strain. ORF 3 nucleotide and amino acid
      sequence identities amongst these isolates (including the Arvac vaccine strain)
      and the Bucyrus reference strain ranged from 85.6 to 98.8%, and 85.3 to 98.2%,
      respectively, whereas ORF 4 nucleotide and amino acid sequence identities ranged
      from 90.4 to 98.3%, and 90.8 to 97.4%, respectively. Phylogenetic tree analysis
      based on the ORF 3 nucleotide sequences showed that the European Vienna isolate
      could be classified into a genetically divergent group from all other isolates
      and the Arvac vaccine strain. In contrast, a phylogenetic relationship among all
      EAV isolates and the Arvac vaccine strain based on the ORF 4 nucleotide sequences
      was observed.

PMID- 9782364
TI  - In vivo tomographic assessment of the heart and blood vessels with intravascular
      ultrasound.
AB  - Intravascular ultrasound (IVUS) has emerged from being a research tool to
      becoming an intrinsic part of modern invasive cardiology mainly due to imaging
      micro anatomy in vivo. For the first time, it is possible to base therapeutic
      decisions not only on lumenograms but also on vessel wall assessment. IVUS has
      both diagnostic and intervention associated potential. The diagnostic strength of
      IVUS is its ability to describe compensatory coronary artery enlargement as a
      response to arteriosclerosis, to assess intermediate lesions, and to reveal
      occult left main stem disease and angiographically "silent" arteriosclerosis. The
      intervention associated potential of IVUS is the optimal device selection, i.e.,
      rotablators in calcified lesions or atherectomy devices in large plaque burden.
      The effects of PTCA on vessel wall morphology can be studied in great detail and
      the effect on luminal gain can be assessed. Several groups have shown that the
      residual plaque area ("plaque burden") even after angiographically successful
      PTCA still lies in the range of 60%. A significant reduction in this number may
      influence long-term outcome after PTCA. Minimal luminal area and residual plaque
      area after PTCA seem to be indicators of restenosis, while the presence or
      absence of dissections seems to be less predictive. The main mechanism of
      restenosis after PTCA is vessel shrinkage, not intimal hyperplasia. Intravascular
      monitoring of stent expansion led to high-pressure stent deployment with a
      significant increase in post-procedural luminal diameters and the ability to
      withhold anticoagulation in patients with optimal stent deployment. In pulmonary
      and aortic diseases, IVUS contributed significantly to the understanding of
      aortic dissection and pulmonary hypertension. Additionally, with intracardiac
      ultrasound left and right ventricular function can be assessed. Intracardiac
      ultrasound has gained clinical usefulness for guiding transcatheter ablation in
      patients with conduction system abnormalities. In the future, integrated devices,
      such as balloons on IVUS catheters, steerable catheters, integrated flow and
      pressure transducers, tissue characterization, and 0.018" IVUS guide wire will
      further enhance the usefulness of IVUS.

PMID- 9782365
TI  - Coronary endothelial dysfunction increases the severity of ischaemia-induced
      ventricular arrhythmias in rat isolated perfused hearts.
AB  - In order to determine the role of coronary vascular endothelial cells in
      generating cardioprotective substances during myocardial ischaemia, rat isolated
      hearts, perfused at constant flow by the Langendorff technique, were subjected to
      treatment with the detergent Triton X100 and the responses of these hearts to a
      30 or 60 min period of coronary artery occlusion was determined. Endothelial
      damage or denudation was shown both by histological examination and by the
      altered vasodilator response to the endothelium-dependent vasodilator bradykinin
      (100 nM), which was reversed to vasoconstriction in hearts treated with Triton X
      100. In contrast, the responses to sodium nitroprusside (100 microM) were
      unimpaired in these hearts and were not different from control responses.
      Ventricular ectopic activity was much more pronounced in hearts with endothelial
      dysfunction (e.g., 3329 +/- 361 ventricular premature beats over a 30 min
      occlusion period compared to 243 +/- 34 in controls; P < 0.01), and the duration
      of ventricular tachycardia was greatly increased (1162 +/- 391 s v 9 +/- 12 s in
      the controls; P < 0.01). Ventricular ectopic activity was still marked when the
      occlusion was prolonged to 1 h and was still apparent at the end of this 1 h
      occlusion period. Reperfusion arrhythmias (ventricular tachycardia and
      ventricular fibrillation) were marked in endothelium-damaged hearts (50%);
      whereas there were no such arrhythmias after a 30 or 60 min occlusion period in
      control hearts. Hearts were also preconditioned by a 3 min coronary artery
      occlusion period 10 min prior to a 30 min coronary artery occlusion. This reduced
      ventricular ectopic activity in both control and endothelium-damaged hearts to
      about the same extent (between 80 and 90% suppression). The results suggest that
      under normal conditions substances generated from endothelial cells protect the
      myocardium against ventricular arrhythmias both during ischaemia and reperfusion.
      However, in this species, preconditioning is still possible in hearts from which
      the coronary vascular endothelium has been removed. If these results can be
      extrapolated to the clinical situation, it suggests that in patients with
      endothelial dysfunction ventricular arrhythmias may be more pronounced following
      a period of ischaemia and especially of reperfusion.

PMID- 9782366
TI  - Effects of chronic noradrenaline on the nitric oxide pathway in human endothelial
      cells.
AB  - Altered endothelium-dependent vasodilation has been observed in congestive heart
      failure (CHF), a disease characterized by a sustained adrenergic activation. The
      purpose of our study was to test the hypothesis that chronically elevated
      catecholamines influence the nitric oxide (NO) pathway in the human endothelium.
      Human umbilical vein endothelial cells (HUVEC) were exposed for 7 days to a
      concentration of noradrenaline (NA, 1 ng/mL) similar to that found in the blood
      of patients with CHF. Kinetics of endothelial constitutive NO synthase (ecNOS)
      and inducible NO synthase (iNOS) activity, measured by [3H]L-arginine to [3H]L
      citrulline conversion, and protein expression of ecNOS and iNOS, assessed by
      Western blot analysis, were unaffected by chronic NA treatment. Furthermore, no
      changes in subcellular fraction-associated ecNOS were found; this indirectly
      shows that chronic NA did not cause phosphorylation of the enzyme. Moreover,
      [3H]L-arginine transport through the plasma membrane was conserved in chronically
      NA-treated cells. The data demonstrate that prolonged in vitro exposure to
      pathologic CHF-like NA does not affect the L-arginine: NO pathway in human
      endothelial cells.

PMID- 9782367
TI  - Coronary endothelial dysfunction after ischemia and reperfusion in the dog: a
      functional and morphological investigation.
AB  - Coronary endothelial dysfunction is characterized by a lower response to
      endothelium-dependent vasodilators such as acetylcholine (ACh) and serotonin
      (5HT), but by an unaltered response to endothelium-independent vasodilators such
      as nitroglycerin (NTG). In the present study, we investigated the vasoreactivity
      of the coronary bed in vivo, in a dog model of ischemia and reperfusion (I/R). We
      also assessed the morphology of the subepicardial arterioles and capillary bed by
      means of scanning electron microscopy (SEM). Anesthetized, instrumented dogs were
      divided in two groups. One group (N = 27) was submitted to ischemia (60 min) and
      reperfusion (180 min) of the left circumflex coronary artery, the second group (N
      = 8) was sham-operated. Prior to and following I/R, ACh, 5-HT, and NTG were given
      intracoronarily. At the end of the experiment a 1 cm3 myocardial biopsy was
      processed for SEM. The sham-operated dogs showed a reduction of basal coronary
      flow of 11%, but the vasoreactivity to ACh and 5-HT remained constant. In the I/R
      group, basal coronary flow was reduced by 35% (p < 0.05), and the vasoreactivity
      to ACh and 5-HT, but not to NTG, was significantly blunted. At SEM the arterioles
      of the dogs submitted to I/R showed a marked adhesion of leukocytes associated
      with holes on the endothelial surface, while the capillary bed was free of
      changes and patient. Thus, following I/R, coronary endothelial dysfunction could
      be demonstrated in vivo by the blunting of the vasoreactive responses to two
      different endothelium-dependent vasodilators. The responses to NTG were not
      affected, probably because the function of the smooth muscle cell was preserved,
      and the capillary bed was patent.

PMID- 9782368
TI  - Endogenous adenosine suppresses norepinephrine-induced ventricular arrhythmias in
      rat heart.
AB  - Adenosine is an antiarrhythmic substance particularly effective in catecholamine
      dependent tachycardias. Although endogenous adenosine substantially accumulates
      in catecholamine-stimulated hearts, little is known about the antiarrhythmic
      potency of endogenous adenosine in this condition. Therefore, we sought to
      demonstrate a potential antifibrillatory effect of endogenous adenosine either by
      blockade of adenosine receptors with 8-phenyltheophylline (8-PT) or by
      suppression of endogenous adenosine release with nitrobenzyl-6-thioinosine
      (NBTI). The study was performed in spontaneously beating Langendorff-perfused rat
      hearts. Adenosine release into the effluent was determined by HPLC methods.
      Catecholamine stimulation was induced by perfusing the hearts with norepinephrine
      (1 mumol/l) for 30 min, which caused ventricular tachycardia (VT) in 31% and
      ventricular fibrillation (VF) in 25% of control hearts (n = 35). When 8-PT (10
      mumol/l) was added to the perfusion buffer prior to norepinephrine, the incidence
      of VT and VF increased to 79 and 68%, respectively. The addition of 8-PT did not
      affect the catecholamine-dependent formation of adenosine. Perfusion of the
      hearts with NBTI (10 mumol/l) prior to norepinephrine reduced adenosine release
      and increased the occurrence of both VT (65%) and VF (40%). In summary, the
      results indicate that adenosine is an endogenous antiarrhythmic substance, which
      accumulates in catecholamine-stimulated myocardium to a level, which effectively
      suppresses the occurrence of ventricular arrhythmias.

PMID- 9782369
TI  - Ultrastructural study of calcium shift in ischemic/reperfused rat heart under
      treatment with dimethylthiourea, diltiazem and amiloride.
AB  - Among factors underlying reperfusion injury are oxygen free radicals and Ca2+
      influx via gated calcium channel or via Na+/H(+)-Na+/Ca2+ exchange which lead to
      calcium overload. The aim of the study was to ultrastructurally visualize the
      distribution of Ca2+ and to compare binding of calcium by the sarcolemma and
      calcium accumulation in mitochondria under therapy with an OH scavenger,
      dimethylthiourea (DMTU), Na+/H+ exchange inhibitor, amiloride, and calcium
      channel blocker, diltiazem, given alone or in combination to ischemic/reperfused
      hearts. Isolated working hearts subjected to 40 min ischemia and 30 min
      reperfusion were perfused with drugs added to the perfusate 15 min before
      ischemia and administered for the rest of the perfusion period. The cytochemical
      phosphate pyroantimonate method for localization of Ca2+ was used, and calcium
      distribution was analyzed with a computer image analyzer. All drugs given alone
      improved sarcolemmal ability to bind calcium. The best results were obtained with
      amiloride. All of the combined therapies gave even better results, but calcium
      accumulation in mitochondria diminished only with diltiazem therapy given alone
      or in combination with DMTU. Since the presence of Ca2+ deposits on the
      sarcolemma is believed to represent its normal function, and calcium
      sequestration by mitochondria reflects an increase in cytosolic calcium load, the
      lack of correlation between sarcolemmal and mitochondrial Ca2+ distribution might
      suggest impaired mechanisms of lowering cytoplasmic calcium or the existence of
      some mechanism other than Na+/Ca2+ exchange, mediated by activated Na+/H+
      exchange.

PMID- 9782370
TI  - Nitric oxide enhances the inotropic response to beta-adrenergic stimulation in
      the isolated guinea-pig heart.
AB  - Nitric oxide (NO) exerts several effects on myocardial contraction, including
      enhancement of relaxation and diastolic function, modulation of beta-adrenergic
      inotropic responses, and inotropic effects in the absence of agonist pre
      stimulation. Different effects have been observed in different species and
      preparations, and it is unclear whether they are species- or preparation
      specific, or whether they represent a range of responses that can manifest in
      most mammalian species. We therefore examined the effects of NO on the inotropic
      response to beta-adrenergic stimulation in the isolated guinea-pig heart, a
      species in which we have previously shown that NO enhances basal left ventricular
      (LV) relaxation and modulates the Frank-Starling response. Isolated ejecting
      hearts were perfused with Krebs buffer at constant placed heart rate (1 microM)
      indomethacin, 37 degrees C, constant loading conditions), and high fidelity LV
      pressure was monitored by an apical 2 F Millar catheter. All hearts were
      initially treated with dobutamine (0.1 microM) and then, once the peak inotropic
      and chronotropic response had been established, with either (a) no further
      treatment (n = 6), (b) the NO donor sodium nitroprusside (1 microM, n = 6; 10
      microM, n = 6), or (c) the specific agonist for NO release, substance P (0.1
      microM, n = 6). Dobutamine (0.1 microM) produced a rapid positive inotropic and
      chronotropic response, associated with a fall in LV end-diastolic pressure
      (LVEDP) and a rise in coronary flow. The positive inotropic effect of dobutamine
      declined over 20-28 minutes, while the chronotropic response persisted over this
      period. Low dose sodium nitroprusside (1 microM) delayed the decline in the
      inotropic response to dobutamine and exaggerated the fall in LVEDP. Similar
      effects were observed with substance P (0.1 microM). In contrast, a higher dose
      of sodium nitroprusside (10 microM) did not alter the response to dobutamine.
      These data indicate that "low dose" NO augments the inotropic response to beta
      adrenergic stimulation in the isolated ejecting guinea-pig heart, in addition to
      its previously reported effects on basal LV relaxation in the same preparation.

PMID- 9782371
TI  - Generating and influencing Torsades de Pointes--like polymorphic ventricular
      tachycardia in isolated guinea pig hearts.
AB  - Torsades de Pointes (TdP) is a polymorphic ventricular arrhythmia which can
      degenerate into ventricular fibrillation. The most typical symptom of TdP is the
      ECG morphology where QRS complexes seem to rotate around the isoelectric
      baseline. Bradycardia and delayed repolarization are regarded as pathophysiologic
      predispositions. For better understanding of the pathophysiology and the
      evaluation of therapeutic or proarrhythmic potential of drugs, a functional
      experimental model is needed. In the present study, an experimental model of
      polymorphic tachyarrhythmias taken as TdP equivalents in isolated guinea pig
      hearts was developed. The hearts were perfused by the Langendorff technique.
      Bradycardia was induced by dissection of the sinus node, and prolongation of the
      QT interval by infusion of two inhibitors of the sodium channel inactivation,
      veratridine and DPI 201-106. TdP equivalents were triggered reproducibly by
      application of electrical single stimuli at the end of the T wave. Experiments
      with different concentrations of the channel active substances alone and in
      combination, with different perfusion times and mode of electrical stimulation
      (single pulse versus train stimulation), showed the highest incidence for TdP
      equivalents by means of an initial 30 min long infusion of 0.5 microM each
      veratridine and DPI 201-106 in combination with electrical single stimuli. After
      finishing the infusion with the channel active substances but still with lasting
      effects from them. TdP equivalents were triggered repeatedly in five of six
      experiments. The reasons for this increased TdP susceptibility after finishing
      the infusion are not known. In a separate series of six similarly arranged
      experiments, the incidence for TdP equivalents could be decreased from 83% to
      12.5% (p < 0.001) by increasing the concentration of magnesium in the perfusate
      from 1.17 to 5.0 mM. With these experiments, the clinically known therapeutic
      effect of magnesium suppressing TdP could be demonstrated in an in vitro model
      for the first time. The results suggest that this model could be used as a base
      for further studies of clinical relevant drugs, especially antiarrhythmic agents,
      to obtain hints of possible risks of proarrhythmic effects or of suitability for
      therapeutic use at TdP attacks.

PMID- 9782372
TI  - The expression of beta 1 integrins in human coronary artery.
AB  - The beta 1 integrin adhesion receptors mediate the binding of cells to
      extracellular matrices, facilitating their growth, migration, and capacity to
      deposit matrix proteins: important factors in arterial restenosis and
      atherosclerosis. The expression of integrins in human coronary artery is,
      however, unexplored. The aim of the current study was, therefore, to define the
      expression of beta 1 integrins by cultured human coronary artery vascular smooth
      muscle cells (hCAVSMC) and in normal human coronary artery; confirming whether or
      not this differs from the repertoire found in other species and human vessels.
      The expression of beta 1 integrins by hCAVSMC was assessed by immuno
      precipitation and the alkaline phosphatase anti-alkaline phosphatase (APAAP)
      immunochemical technique. In addition, mRNA expression was defined by reverse
      transcription polymerase chain reaction (RT-PCR). Normal adult human coronary
      arteries (n = 4) were also stained by the APAAP method. In vitro hCAVSMC express
      alpha 2 beta 1 (a collagen and occasional laminin receptor) and alpha 5 beta 1 (a
      fibronectin receptor) with lesser expression of alpha 3 beta 1 (a multifunctional
      receptor). They do, however, possess mRNA for several other integrins. Cells
      within the media of human coronary artery wall express alpha 3 beta 1 and alpha 5
      beta 1 but not alpha 2 beta 1: instead the alternative collagen/laminin receptor,
      alpha 1 beta 1, is expressed in vivo. This pattern of expression differs subtly
      from that described in rats through it closely parallels that found in other
      human arteries.

PMID- 9782373
TI  - Adenosine attenuates in vivo myocardial stunning with minimal effects on cardiac
      energetics.
AB  - Adenosine has been shown to modulate myocardial intermediary metabolism. The
      purpose of this study was to determine whether adenosine-mediated attenuation of
      in vivo myocardial stunning is associated with improved myocardial
      phosphorylation potential. Adult, open chest pigs were subjected to 10 minutes of
      regional myocardial ischemia and 90 minutes reperfusion. Regional ventricular
      function was assessed by measuring systolic wall thickening. Myocardial
      phosphorylation potential was estimated from the tissue (CrP/CrxPi) ratio
      determined in rapid-frozen tissue biopsy samples from normal and stunned
      myocardium. Control pigs were compared to animals treated prior to ischemia with
      intracoronary adenosine (50 micrograms/kg/min). Postischemic regional systolic
      wall thickening in adenosine treated pigs was significantly improved (40 +/- 3%
      of preischemic values) compared to control untreated pigs (26 +/- 3%). Myocardial
      stunning was associated with decreased ATP levels, but neither the total creatine
      pool (CrP + Cr) nor the (CrP/CrxPi) ratio was reduced. Adenosine pretreatment was
      associated with decreased Pi and Cr contents resulting in improved postischemic
      (CrP/CrxPi) ratio in the stunned bed compared to controls, but this effect
      occurred only after postischemic function had attained maximal improvement. These
      results suggest that adenosine attenuation of in vivo myocardial stunning is
      independent of elevated myocardial phosphorylation potential.

PMID- 9782374
TI  - Post-ejection thickening as a marker of viable myocardium. An echocardiographic
      study in patients with chronic coronary artery disease.
AB  - The study aim was to assess whether post-ejection thickening (PT) is an useful
      marker of viable myocardium in patients with chronic coronary artery disease.
      Twenty-three patients with critical coronary stenoses were submitted to
      dobutamine and dipyridamole stress-echocardiographies and dipyridamole-early
      redistribution 201Tl SPECT within 15 days from coronary arteriography. They were
      selected for the presence of PT in segments that could be optimally studied by M
      mode echocardiography and were hypo-akinetic in basal conditions. PT (occurring
      between end-ejection and mitral valve opening) was found in 58% of dysfunctional,
      critically perfused regions. Ninety-eight percent of the regions with PT and 6%
      of those without PT improved during low-dose dobutamine stress-echocardiography.
      Segments with PT had, respectively, higher and lower SPECT early-redistribution
      thallium activity than dysfunctional segments without PT and normokinetic
      regions. Therefore, regions with PT were viable and had a moderate decrease in
      coronary perfusion. Akinetic segments without PT did not show any inotropic
      reserve. After revascularization almost all the segments with PT improved. In
      conclusion, PT is a pattern of myocardial contraction easily detected by M-mode
      echocardiography in the clinical setting. If the results of this study are
      further confirmed, PT may become a sign for the recognition of myocardial
      viability.

PMID- 9782376
TI  - Mechanosensitive ion channels and their mode of activation.
AB  - Mechanosensitive channels are ion channels whose activity is dependent on a
      mechanical stress on the membrane. They are believed to play a central role in
      mechanotransduction, the process by which mechanical energy is converted into
      electrical or chemical signals in biological cells. Recent progress, which has
      been made at the molecular level, is presented, and the two current models of
      activation of these channels are discussed.

PMID- 9782377
TI  - FhuA, an Escherichia coli outer membrane protein with a dual function of
      transporter and channel which mediates the transport of phage DNA.
AB  - FhuA (M(r) = 78,900) is an Escherichia coli outer membrane protein which
      transports the ferric siderophore ferrichrome and is the receptor for phage T5,
      phi 80 and T1 and for colicin M. FhuA was purified chromatographically in non
      ionic detergent (octyl glucoside). The circular dichroism spectrum indicates that
      FhuA is essentially organized in beta-strands like the majority of proteins of
      the outer membrane of Gram-negative bacteria. The structural parameters of FhuA
      were assessed from size exclusion chromatography, sedimention equilibrium and
      velocity experiments. FhuA is monomeric in solution and functional since binding
      of phage T5 causes the release of the phage genome, a double-stranded DNA of
      121,000 base pairs, into the surrounding medium. Planar lipid bilayer experiments
      showed that the FhuA transporter is converted into a high conductance channel
      upon binding of phage T5. FhuA was reconstituted into large unilamellar vesicles
      (mean diameter 125 nm). Cryo-electron microscopy and fluorescence experiments,
      using a DNA intercalant YO-PRO 1, showed that binding of T5 to FhuA triggers the
      transfer of the phage genome into the proteoliposomes without altering their
      morphology. Two models can account for these observations, which apply both to in
      vitro and in vivo DNA transport. The simplest model supposes that the naked DNA
      is transported through the FhuA channel. Alternatively transfer of DNA might be
      mediated by pb2, the protein forming the phage straight fiber. pb2 would insert
      either directly in the membrane or inside the FhuA channel.

PMID- 9782378
TI  - Physical techniques for the study of exocytosis in isolated cells.
AB  - Membrane traffic is an important aspect of cell biology which implies shuttle
      vesicles and multiple binding/fusion events. In spite of rapid progress at the
      biochemical level, the mechanism of fusion is still not understood. A detailed
      physical description of the phenomenon is possible at the level of the plasma
      membrane where secretory vesicles fuse with the cell membrane, a process known as
      exocytosis. This process is specially active in neurons (release of
      neurotransmitter) and in endocrine cells (release of hormones), where exocytosis
      is tightly regulated. Among the biophysical techniques developed, cell membrane
      capacitance measurements by the technique of patch-clamp and amperometry of the
      oxidizable secretory products have resulted in interesting information. These
      techniques have described the initial fusion pore, its fluctuations, the efflux
      of material through the pore and its irreversible expansion. Optical techniques,
      using bioluminescent and fluorescent probes are also in progress. For instance,
      the dye FM 1-43 binds to but is not translocated through biological membranes and
      it has been used to measure membrane surface, as done by capacitance measurement.
      Evanescent wave fluorescence microscopy has been recently introduced to analyse
      the behaviour of secretory granules in the vicinity of the plasma membrane.

PMID- 9782380
TI  - Study of the behavior of biological molecules in a thin gap by refractive index
      and force measurements with an automatic surface force apparatus.
AB  - The automation of the mica surface displacement of a surface force apparatus
      (SFA) increases the accuracy of the intermolecular force measurements that is
      obtained without the presence of the experimenter. The automatic device cancels
      any thermal drift and the stability of the mica surfaces is optimum. The distance
      between the mica surfaces is measured by Tolansky multiple-beam interferometry
      (FECO method) which offers a sensitivity of 0.1 nm in the direction perpendicular
      to the plane of contact area. The mean refractive index of the medium between the
      mica plates is computed from simultaneous measurements of the wavelengths of two
      successive fringes of equal chromatic order (FECO). A conversion of an isotropic
      molecule to another anisotropic molecule can be identified from the variations of
      the refractive index. In good conditions, we can compute the local concentration
      of the molecules in the gap of the device, and estimate the Young's modulus of a
      protein.

PMID- 9782379
TI  - Biomedical applications of maghemite ferrofluid.
AB  - The use of cell-targeted ferrofluid in the characterization of modifications of
      cell membranes is reviewed. Maghemite ferrofluid was synthesized by the Massart
      method, complexed with dimercaptosuccinic acid (FF). Cell targeting by FF was
      developed by coupling FF to various biological effectors such as antibodies,
      lectins, etc, which enabled magnetic cell sorting. Modifications in erythrocyte
      membranes were studied using FF bound to recombinant human annexin V (AnxFF)
      which is very sensitive, compared to other Anx-based reagents, in the early
      detection of phosphatidylserine (PS) exposition on the outer leaflet of the
      plasma membrane. Thus PS exposition on mouse RBC was detected already after a 24
      h storage at 4 degrees C and, transiently, 24 h after their infection by
      Plasmodium parasites, at which time the parasites are still confined to the
      liver, thus leading to the recruitment of young RBC and the accumulation of a
      species, intermediate between reticulocytes and erythrocytes, and the actual RBC
      target of plasmodial invasion. AnxFF revealed PS exposition on RBC from sickle
      cell anemia patients, following various inflammations and already after 20 days
      of human blood storage under blood bank conditions. Such a sensitive detection
      should be similar to that of macrophages which recognize exposed PS on cells and
      bring about the latter's elimination from the circulation. AnxFF binding
      determination was combined with that of cell electrophoretic mobility, glycerol
      resistance and filterability to characterize RBC membrane modifications in
      Alzheimer's disease patients which suggested a continuous damage and regeneration
      in RBC of these patients. A logistic analysis suggested that several three
      parameter combinations could permit diagnosis of Alzheimer's disease with up to
      95% accuracy. THP1 cells and macrophages, derived themselves by incubation with
      retinoic acid, were bound to FF and placed in a radio frequency alternating
      magnetic field. Magnetocytolysis was associated with FF attachment to the cells
      without damage to non-bound cells and without heating of the surrounding
      solution.

PMID- 9782381
TI  - Mechanical properties of model membranes studied from shape transformations of
      giant vesicles.
AB  - Membrane deformations occur frequently in cell functioning. From the physical
      point of view, the understanding of such shape changes requires the introduction
      of mechanical parameters like bending elasticity. In this article it is shown how
      this physical property can be obtained from the analysis of small or large shape
      transformations from giant vesicles. Then it is demonstrated that the bending
      modulus is strongly dependent on the membrane composition and environmental
      conditions. This is the case for one-component bilayers
      (dilauroylphosphatidylcholine (DLPC), dimyristoylphosphatidylcholine (DMPC),
      dipalmitoylphosphatidylcholine and stearoyloleoyl-phosphatidylcholine (SOPC) and
      for two-component lipid mixtures (DMPC/cholesterol, DLPC/dilauroylphosphatidic
      acid). Further it is shown that the bending elasticity of natural lipid extracts
      (egg phosphatidylcholine, digalactosyl diglyceride and red blood cell lipid
      extracts) is generally smaller than that of comparable synthetic model membranes.
      The role of transmembrane proteins is examined by measuring the bending
      elasticity of SOPC/gramicidin mixtures. Finally, larger scale shape
      transformations of giant vesicles under an alternative electric field are
      discussed.

PMID- 9782382
TI  - Molecular dynamics simulation of POPC at low hydration near the liquid crystal
      phase transition.
AB  - We report results of a preliminary molecular dynamics study of a 1-palmitoyl-2
      oleoylphosphatidylcholine (POPC) bilayer at low hydration (5% in weight). Our
      results suggest a gel phase structure where the oleic chain is bent recalling the
      crystalline oleic acid structure. We have also found a discontinuity in the
      volume/temperature curve which might be related to the gel to liquid crystal
      phase transition in POPC.

PMID- 9782383
TI  - Self-evolving microstructured systems upon enzymatic catalysis.
AB  - The consequences of cell microstructuration on enzyme functions is discussed in
      the framework of self-evolving microstructured systems. Molecular assemblies of
      amphiphiles or lipids are spontaneously formed by self-organisation. Among these
      different structures, reversed micelles, liquid crystalline mesophases and
      vesicles are hosts for enzymatic reaction studies. Inside a living cell,
      phospholipid metabolism is responsible for membrane structural modifications; the
      catalytic behaviour of lipolytic enzymes, mainly phospholipase (PL) A2, is
      described in relation with structural aspects of biological membranes. The
      implication in cellular regulation events of PLC and PLD is discussed in relation
      with the role of their reaction products as second messengers in membrane fusion
      processes. The in vitro synthesis of dialkyl phosphatidylcholines, via the
      enzymatic 'salvage pathway' which leads to the formation of vesicles upon
      phospholipid formation, is considered in relation with autopoiesis. More recent
      studies on self-evolving systems based on enzyme-surfactants reactions are
      detailed. The interactions between amphiphilic aggregates and enzymes allow to
      explore the OG/octanol/water phase diagram. Enzymatic formation of
      dipalmitoylphosphatidylcholine (DPPC) liposomes and non-ionic surfactant vesicles
      (NSV), starting from mixed micelles or open structures, finally sets an example
      of a biomimetic self-evolving system.

PMID- 9782384
TI  - Solid-state NMR for the study of membrane systems: the use of anisotropic
      interactions.
AB  - The use of solid-state nuclear magnetic resonance (NMR) as a tool to determine
      the structure of membrane molecules is reviewed with a particular emphasis on
      techniques that provide information on orientation or order. Experiments reported
      here have been performed in membranes, rather than in micelles or organic
      solvents. Several ways to prepare and handle the samples are discussed, like
      sample orientation and magic-angle spinning (MAS). Results concerning lipids,
      membrane peptides and proteins are included, as well as a discussion regarding
      the potential of such methods and their pitfalls.

PMID- 9782385
TI  - 1H- and 2H-NMR studies of a fragment of PMP1, a regulatory subunit associated
      with the yeast plasma membrane H(+)-ATPase. Conformational properties and lipid
      peptide interactions.
AB  - PMP1 is a 38-residue polypeptide associated with the yeast plasma membrane H(+)
      ATPase, found to regulate the enzyme activity. To investigate the molecular basis
      of the PMP1 biological function, the conformational properties of a synthetic
      PMP1 fragment, A18-F38, comprising the predicted C-terminal cytoplasmic domain
      and a part of the transmembrane anchor have been studied by 1H- and 2H-NMR
      spectroscopies. High resolution 1H-NMR experiments showed that, in deuterated DPC
      micelles, the A18-G34 segment adopts a well defined helix conformation. Our data
      suggest that the whole PMP1 molecule forms a unique helix whose axis might be
      slightly tilted with respect to the bilayer normal. Protonated DPC, DMPC and DMPS
      were incorporated in deuterated micelles containing the PMP1 fragment for
      studying lipid-peptide interactions. Unusually strong and selective
      intermolecular NOEs between lipid chain and peptide side chain protons,
      especially those of the unique Trp residue, were observed. Solid state 2H-NMR
      experiments performed on pure deuterated POPC and mixed deuterated POPC:POPS
      (5:1) bilayers revealed that the PMP1 fragment specifically interacts with
      negatively charged PS lipids.

PMID- 9782386
TI  - Hydrophobically driven attachments of synthetic polymers onto surfaces of
      biological interest: lipid bilayers and globular proteins.
AB  - This paper gives a brief overview of the consequences of associations between
      amphiphilic water-soluble polymers and small colloidal particles of biological
      interest: proteins and vesicles. Typical structures of water-soluble synthetic
      polymers containing hydrophobic groups are presented. The segregation between
      polar and apolar units in these polymers induces self-organisation in micro
      domains despite the lack of specific primary structure. In the presence of other
      amphiphilic particles like proteins and vesicles, mixed assemblies are formed.
      Examples of polymer associations with vesicles or globular proteins, mainly
      focused on the acrylic derivatives, bring out common features in these mixtures.
      When the size of the polymer is of the same order of magnitude as that of the
      particle, adsorption of polymer chains creates a protective layer around each
      individual particle. Depending on the hydrophobicity of the partners, the
      association can stabilise the dispersion of unmodified particles or induce
      structural changes (membrane disruption, leakage). When small particles are added
      to solutions of long polymers, multimolecular complexation occurs. In this case,
      the size of the resulting aggregates depends on the concentrations. It goes from
      the size of one polymer molecule up to formally infinity as revealed by gelation.
      The identification of non-specific association modes between biological
      nanoparticles and macromolecules might be revealed by the general behaviour of
      these synthetic mixed systems.

PMID- 9782387
TI  - Scanning transmission electron microscopy study of the molecular mass of
      amphipol/cytochrome b6f complexes.
AB  - The composition and mass of complexes between Chlamydomonas reinhardtii
      cytochrome b6f and low molecular mass amphipathic polymers ('amphipols') have
      been studied using biochemical analysis and scanning transmission electron
      microscopy at liquid helium temperature (cryo-STEM). Cytochrome b6f was trapped
      by amphipols either under its native 14-meric state or as a delipidated, lighter
      form. A good consistency was observed between the masses of either form
      calculated from their biochemical composition and those determined by cryo-STEM.
      These data show that association with amphipols preserved the original original
      state of the protein in detergent solution. Complexation with amphipols appears
      to facilitate preparation of the samples and mass determination by cryo-STEM as
      compared to conventional solubilization with detergents.

PMID- 9782389
TI  - Highly fluorinated amphiphiles and colloidal systems, and their applications in
      the biomedical field. A contribution.
AB  - Fluorocarbons and fluorocarbon moieties are uniquely characterized by very strong
      intramolecular bonds and very weak intermolecular interactions. This results in a
      combination of exceptional thermal, chemical and biological inertness, low
      surface tension, high fluidity, excellent spreading characteristics, low
      solubility in water, and high gas dissolving capacities, which are the basis for
      innovative applications in the biomedical field. Perfluoroalkyl chains are larger
      and more rigid than their hydrogenated counterparts. They are considerably more
      hydrophobic, and are lipophobic as well. A large variety of well-defined, modular
      fluorinated surfactants whose polar head groups consist of polyols, sugars, sugar
      phosphates, amino acids, amine oxides, phosphocholine, phosphatidylcholine, etc,
      has recently been synthesized. Fluorinated surfactants are significantly more
      surface active than their hydrocarbon counterparts, both in terms of
      effectiveness and of efficiency. Despite this, they are less hemolytic and less
      detergent. Fluorosurfactants appear unable to extract membrane proteins.
      Fluorinated chains confer to surfactants a powerful driving force for collecting
      and organizing at interfaces. As compared to non-fluorinated analogs,
      fluorosurfactants have also a much stronger capacity to self-aggregate into
      discrete molecular assemblies when dispersed in water and other solvents. Even
      very short, single-chain fluorinated amphiphiles can form highly stable, heat
      sterilizable vesicles, without the need for supplementary associative
      interactions. Sturdy microtubules were obtained from non-chiral, non-hydrogen
      bonding single-chain fluorosurfactants. Fluorinated amphiphiles can be used to
      engineer a variety of colloidal systems and manipulate their morphology,
      structure and properties. Stable fluorinated films, membranes and vesicles can
      also be prepared from combinations of standard surfactants with
      fluorocarbon/hydrocarbon diblock molecules. In bilayer membranes made from
      fluorinated amphiphiles the fluorinated tails segregate to form an internal
      teflon-like hydrophobic and lipophobic film that increases the stability of the
      membrane and reduces its permeability. This fluorinated film can also influence
      the behavior of fluorinated vesicles in a biological milieu. For example, it can
      affect the in vivo recognition and fate of particles, or the enzymatic hydrolysis
      of phospholipid components. Major applications of fluorocarbons currently in
      advanced clinical trials include injectable emulsions for delivering oxygen to
      tissues at risk of hypoxia; a neat fluorocarbon for treatment of acute
      respiratory failure by liquid ventilation; and gaseous fluorocarbon-stabilized
      microbubbles for use as contrast agents for ultrasound imaging. Fluorosurfactants
      also allow the preparation of a range of stable direct and reverse emulsions,
      microemulsions, multiple emulsions, and gels, some of which may include
      fluorocarbon and hydrocarbon and aqueous phases simultaneously. Highly
      fluorinated systems have potential for the delivery of drugs, prodrugs, vaccines,
      genes, markers, contrast agents and other materials.

PMID- 9782388
TI  - Synthetic neoglycolipids for biological applications: correlation between their
      structures and their interactions with membrane proteins.
AB  - Synthetic glycolipids are of interest for their biological applications requiring
      interactions with membrane proteins. Depending on their structures, new series of
      glycolipids have applications in extraction of membrane proteins or medical
      applications as mimics of natural ligands of proteins.

PMID- 9782390
TI  - Stabilization of integral membrane proteins in aqueous solution using fluorinated
      surfactants.
AB  - Surfactants carrying either a hydrocarbon or a fluorocarbon alkyl chain have been
      synthesized. The polar head was either tris(hydroxymethyl)acrylamidomethane
      (THAM), telomerized THAM, or a glycosylated THAM moiety. The aqueous solubility
      of some of these molecules was increased by oxidizing to a sulfoxide the
      thioether function that associates their hydrophobic and hydrophilic moieties. In
      all cases, the critical micellar concentration was principally determined by the
      length and chemical nature of the alkyl chain. The usefulness of these
      surfactants in handling integral membrane proteins in solution has been examined
      using as test materials chloroplast thylakoid membranes and the photosynthetic
      complex cytochrome b6f. In keeping with earlier observations in other systems,
      none of the fluorinated surfactants was able to solubilize thylakoid membranes.
      Transfer to a solution of fluorinated surfactant of b6f complexes that had been
      solubilized and purified in the presence of a classical detergent usually
      resulted in aggregation and precipitation of the protein, while most homologous
      molecules with hydrocarbon chains did keep the b6f complex soluble. Two of the
      fluorinated surfactants, however, proved able to maintain the b6f complex water
      soluble, intact, and enzymatically active. Because of their limited affinity for
      lipid alkyl chains and other hydrocarbon surfaces, fluorinated surfactants appear
      as potentially interesting tools for the study of membrane proteins that do not
      stand well exposure to classical detergents.

PMID- 9782391
TI  - Perfluoroalkylphosphocholines are poor protein-solubilizing surfactants, as
      tested with neutrophil plasma membranes.
AB  - We have tested the membrane-protein solubilizing properties of two
      perfluoroalkylphosphocholines. These compounds belong to a series of fluorinated
      amphiphiles which are being investigated as potential stabilizing agents for a
      variety of fluorocarbon-based systems. We are particularly interested in
      cytochrome b558 from phagocytes, the redox component of NADPH oxidase. Its heavy
      subunit is believed to carry binding sites for NADPH and FAD. Nevertheless, when
      the cytochrome is purified in the presence of classical detergents, it carries no
      FAD. This could be due to a delipidating, denaturing effect of these detergents
      (octyl glucoside, Triton, etc). The first perfluoroalkyphosphocholine,
      C8F17(CH2)2O-P(O2-)-O(CH2)2N+(CH3)3(F8C2PC), extracted about as much protein from
      neutrophil plasma membranes into a 100,000 g supernatant as octyl glucoside. The
      second compound, C8F17(CH2)11O-P(O2-)-O(CH2)2N+(CH3)3(F8C11PC), was less
      efficient. We found that flavin was still protein-bound in the crude F8C2PC
      extract at a FAD to heme ratio of about 1, and a good NADPH oxidase activity was
      obtained without addition of exogenous FAD, even after dialysis or gel
      filtration, whereas dialysis eliminated most of the FAD from the octyl glucoside
      extracts. These experiments appeared to make F8C2PC an interesting membrane
      solubilizing agent. Nevertheless, no protein in the F8C2PC extract could be
      adsorbed on the chromatographic supports normally used for purification. After
      dilution of the extract and addition of 15 mM octyl glucoside, some of the
      proteins, such as myeloperoxidase, could be adsorbed (and eluted), but not
      cytochrome b558. Freeze-fracture electron microscopy showed that the F8C2PC
      extracts contained numerous vesicles and aggregates of small shapeless particles.
      Higher centrifugal forces sedimented most proteins of the 100,000 g supernatant.
      As a check, the effect of F8C2PC was tested on sarcoplasmic reticulum vesicles,
      the behavior of which with respect to the usual non-denaturating detergents has
      been well studied. There was little, if any, solubilization. We conclude that,
      although supernatants of F8C2PC extracts of neutrophil membranes are optically
      clear, proteins are not really solubilized. This result is in keeping with the
      absence of lytic effects of F8C2PC on erythrocyte membranes.

PMID- 9782392
TI  - Detergent binding in trigonal crystals of OmpF porin from Escherichia coli.
AB  - The structure of the detergent, ocytyl hydroxyethylsufoxide (C8(HE)SO), bound to
      the OmpF porin from E coli (in the trigonal crystal form) has been determined by
      neutron crystallography. Due to a dynamic exchange of detergent molecules with
      their environment they are not ordered on an atomic scale. The structure reported
      here is therefore at a resolution of approximately 16 A. The X-ray
      crystallographically determined structure of the protein provides a starting
      point for the neutron analysis in which the detergent is visualized primarily
      thanks to its high contrast against D2O. The structure shows the detergent to be
      located mainly in two areas. It forms toroidal annuli around each OmpF trimer,
      these annuli fusing to form a detergent belt surrounding a solvent filled column
      traversing the crystal. Those areas of the protein to which the detergent binds
      are formed almost exclusively of hydrophobic residues and form a band about 30 A
      high around the trimer. Its upper and lower bounds are defined by two bands of
      aromatic residues, tyrosines pointing away from the detergent belt and
      interacting with the polar headgroups while phenylalanines point inwards. This
      strongly suggests that the same areas define, in vivo, the location at which
      protein interacts with lipid. The hydrophobic moiety of detergent is also found
      mediating the hydrophobic protein-protein interactions at the interface between
      two trimers on the crystallographic two-fold axis.

PMID- 9782393
TI  - Crystallographic analysis of freeze-fractured three-dimensionally ordered
      specimens.
AB  - We describe here an original approach for solving the structure of three
      dimensionally ordered specimens at low and medium resolutions. It combines freeze
      fracture electron microscopy and quantitative image processing and has been first
      successfully applied to the crystallographic study of different lipid-containing
      cubic phases. The structure preservation during cryofixation is controlled by
      recording X-ray diffraction before and after freezing. Well frozen cubic phases
      show fracture planes which look like well defined cleavage planes of 3-D
      crystals. These fracture planes (domains) reveal a mosaic of 2D ordered sub
      domains which are geometrically related to each other by simple crystallographic
      operations. The symmetry properties of the images mirror faithfully the symmetry
      of the space groups. The shifts and rotations observed between adjacent sub
      domains are related to this symmetry. Different cubic phases display different
      fracture behavior, highly characteristic for a given space group. Interpretation
      of the averaged images of different domains in terms of molecular structure is
      done by the comparison of the averaged periodic motifs either with the
      corresponding sections of the electron density map (from X-ray diffraction data)
      or with the corresponding sections of a 3-D-space filling model. We show here
      that the same procedure may be applied to other three-dimensionally ordered
      specimens such as 3-D crystals of membrane proteins or of other proteins,
      including naturally occurring protein crystals of some secretory organelles.
      Finally, the same approach could also provide a powerful tool for the study of
      membrane protein crystallogenesis, particularly for the formation of 3-D
      crystals.

PMID- 9782394
TI  - Heterologous expression of G-protein-coupled receptors: human opioid receptors
      under scrutiny.
AB  - G-protein-coupled receptors whose topology shows seven transmembrane domains form
      the largest known family of receptors involved in higher organism signal
      transduction. Despite increasing knowledge on the functioning mechanisms of these
      receptors, almost no structural data are available but only a few models.
      Structural studies using a wide range of physical and biochemical techniques may
      require fairly large (up to several milligrams) amounts of purified protein.
      Since such quantities are not naturally available, overexpression is
      prerequisite. Heterologous expression systems are then assayed for maximal
      production of a protein facsimile. Heterologous systems may also provide
      interesting alternatives for receptor functional studies in a different cellular
      context. Opioid receptors will be used as an example to discuss aspects related
      to the choice and suitability of several different expression systems for the
      intended analysis of G-protein-coupled receptor properties. General implications
      will be outlined.

PMID- 9782395
TI  - [Methicillin-resistant Staphylococcus aureus (MRSA)--clinical implications].
AB  - The isolation rate of MRSA from Staphylococcus aureus infections rose to 8.7% in
      German hospitals between 1990 and 1995. Patients undergoing surgical treatment or
      physiotherapy showed a threefold increase in the risk of being colonized or
      infected with MRSA. Surgical wound infection is the most frequent among MRSA
      induced infections (28%). The main transmission path of MRSA inside a hospital is
      bacterial spread from one patient to another through contact with the hands of
      nursing staff. Therefore, the crucial strategy in avoiding the spread of bacteria
      is strict hygiene management through hand disinfection. The most widespread
      therapeutic regimen for simultaneous eradication of nasal colonization and
      treatment of infection on other body sites is mupirocin nasal ointment combined
      with parenteral vancomycin application. The non-indicated use of vancomycin,
      e.g., for perioperative prophylaxis or prevention of catheter-induced infections,
      should be avoided, especially after the appearance of vancomycin-intermediately
      sensitive S. aureus (VISA) strains that have been reported recently from Japan
      and the USA.

PMID- 9782396
TI  - ["Streptococcal toxic shock-like syndrome"].
AB  - Since the mid-1980s increasing numbers of severe group A streptococcal infections
      (Streptococcus pyogenes) have been reported worldwide. Younger, healthy patients
      after minor local trauma are most commonly afflicted. The infection is
      characterized by a rapid course with shock, sepsis, multiorgan failure, soft
      tissue infection and a high mortality rate. This special disease has been termed
      "streptococcal toxic shock-like syndrome". The M-proteins, especially types 1 and
      3, and the streptococcal pyrogenic exotoxin A (speA) might play an important role
      in the pathogenesis of the infection. High dose therapy with antibiotics,
      monitoring in the intensive care unit and early, aggressive and often multiple
      debridement of necrotic soft tissue are necessary to save the patient's life.

PMID- 9782397
TI  - [Intra-abdominal abscess].
AB  - In more than 80% of cases, intra-abdominal abscesses derive from an intra
      abdominal organ, and in most cases they develop after operative procedures.
      Regarding anatomy, intra-abdominal abscesses can be divided into intra-peritoneal
      and visceral abscesses and those located in the anterior retroperitoneal space.
      Despite improvements in ultrasonography, CT is still the most effective method in
      diagnosis and therapy. Percutaneous ultrasound or CT-guided drainage is a therapy
      characterized by low procedural morbidity and is successful in 80% of cases if
      strict criteria are met. Complicated abscesses and those cases in which the
      underlying disease has to be treated require surgical intervention. Most liver
      abscesses are treated interventionally; in abscesses of the pancreas or spleen
      and in Crohn's disease, surgery is necessary. The combination with sufficient
      antibiotic drug therapy is very important. Specific infectious diseases appearing
      as intra-abdominal conglomerates (tuberculosis, actinomycosis, amebiasis) lead to
      a delay in diagnostics because of their scarcity and are characterized by special
      patho-anatomical, diagnostic and therapeutic features. The crucial thing is to
      take a specific infection into consideration.

PMID- 9782398
TI  - [Pleural empyema].
AB  - Thoracic empyema may be based on four different etiologic mechanisms of
      infection: (1) parapneumonic, (2) posttraumatic, (3) postspecific, (4)
      postsurgical. According to morphologic processes, three different time-dependent
      stages may be present: (1) exudative phase, (2) fibrino-purulent phase, (3)
      organization and pleural peel formation. Diagnosis and pleural puncture are based
      on the findings of thoracic CT and transthoracic ultrasonography.
      Thoracocentesis, however--even if performed repeatedly--is not an appropriate
      treatment of empyema. Chest tube drainage and irrigation of the pleural cavity is
      appropriate only in stage I and early stage II disease to re-establish total lung
      inflation and healing without pleural peel formation. Selected stage II cases may
      benefit from video-assisted debridement, but a 30% conversion rate to open
      thoracotomy has to be assumed. Residual organized cavities, loculated peels etc.
      require open thoracotomy and empyemectomy, decortication or combined maneuvers.
      For treatment quality and outcome it is not only decisive to remove the source of
      infection but also to reexpand the entire lung without remaining restrictive
      peels and without relevant leaks.

PMID- 9782399
TI  - [Joint empyema].
AB  - Bacterial joint infection is rare but may have an unfavourable functional
      aotcome. The different stages of purulent arthritis, depending on the
      pathophysiological developments, require different treatment measures. Clinical
      examination, analysis of joint tap and arthroscopy are crucial for diagnosis.
      Surgical management comprises: (1) open or arthroscopic debridement with
      intensive flush lavage; (2) postoperative drainage and flush lavage; (3) early
      and continuous active and passive motion. Recovery will be complete only if
      therapy is instituted as early as possible (within 3 days). Joint empyema must
      therefore be treated as a surgical emergency.

PMID- 9782400
TI  - [Explant test with skin and peritoneum of the neonatal rat as a predictive test
      of tolerance of local anti-infective agents in wounds and body cavities].
AB  - In vitro culture of peritoneal explants of neonatal rats after previous
      application of agents simulating wound antisepsis is a sensitive screening method
      for the determination of the tissue compatibility of local wound antiinfectives.
      Two test models are differentiated: (1) separated peritoneal explants as a model
      for chronic or deep wounds and (2) peritoneum in situ in the experimental animal
      with subsequent extraction and cultivation of the explants. Considering the
      present state of knowledge the following conclusions can be drawn regarding
      antisepsis of wounds: Lavasept (0.1%) may be classified as the agent of choice
      for deep and chronic wounds, for drip-suck irrigation and for antiinfective
      lavage of body cavities inclusively for peritoneal lavage (0.05%). Taurolidin is
      antiseptically effective in long term application (> 6 h), and because of its
      antitoxic effect as well as lack of cytotoxicity it is especially suitable for
      peritoneal lavage. Betaisodona solution is very well suited for superficial
      contaminated wounds and can be used in a dilution of 1:10 for short-term rinsing
      of deep wounds, including body cavities but not for peritoneal lavage. Ethanol
      causes no inhibition of explant growth and therefore retains its importance in
      wound antisepsis.

PMID- 9782401
TI  - [Laparoscopic sigmoid resection in diverticulitis].
AB  - Between September 1992 and May 1997 in the Department of Surgery at the Medical
      University of Lubeck 240 colorectal procedures were performed by laparoscopic
      techniques. Fifty-seven patients underwent laparoscopic colectomy for
      diverticulitis. In 52 cases sigmoid resections were performed laparoscopically,
      including 4 cases with simultaneous laparoscopic rectopexy. Anterior resections
      were necessary in 3 patients, whereas 2 patients with extended localization of
      diverticula required left hemicolectomies. Using atraumatic instruments and an
      ultrasound dissector, laparoscopic resection involved tubular dissection and
      preperitoneal anastomosis. The mean operative time was 234 min. In 8 cases (14%)
      conversion to an open procedure was necessary. Complications occurred in 6
      patients (10.5%). One patient died because of an anastomotic leakage. In
      conclusion, with increasing experience laparoscopic resection for diverticulitis
      can be performed without additional morbidity in comparison to open colectomy. In
      particular, the benefits of the minimally invasive method are quicker
      reconvalescence with reduced postoperative pain and improved cosmesis.

PMID- 9782403
TI  - [The new commander is on board!].

PMID- 9782402
TI  - [Risks and benefits of laparoscopic hernia-plasty (TAPP). 5 years experiences
      with 3,400 hernia repairs].
AB  - In the present study, for the first time the aspects of risk, benefit and the
      costs of laparoscopic hernioplasty in the transabdominal technique with
      preperitoneal placement of a polypropylene mesh are examined prospectively in a
      very large group of patients with 3,400 hernia repairs. The median operation time
      was 45 min for unilateral primary hernias, 50 min for unilateral recurrent
      hernias and 76 min for bilateral hernias. The frequency of complications showed a
      significant dependence on the individual steps in the development of the method
      and the individual learning curve. The same is true for the rate of recurrency.
      Whereas initially the rate of serious complications was 2.75%, the rate of minor
      complications 11% and the rate of recurrences 4.5% the corresponding figures are
      at present 0.4%, 4.4% and 0.5%. Laparoscopic hernioplasty proved to be equally as
      effective in the treatment of primary hernias, recurrent hernias and bilateral
      hernias. The large number of 11 surgeons participating proves that laparoscopic
      hernioplasty can be learned and that even in a teaching hospital it can be
      performed safely, efficiently and cost-effectively.

PMID- 9782404
TI  - [Medical principles and medico-legal aspects of the prevention of venous
      thromboembolisms].

PMID- 9782405
TI  - [Legal aspects of prevention of thrombosis. Reliable and controversial aspects of
      thrombosis prevention from the forensic viewpoint].

PMID- 9782406
TI  - [Correction offered].

PMID- 9782407
TI  - [Structured contract for promoting ambulatory surgery by the federal health
      insurance for the Salzgitter district].

PMID- 9782408
TI  - [Long-term experiences with mechanical patient-controlled analgesia pumps for
      therapy of postoperative pain in general surgery].
AB  - The efficiency and safety of patient-controlled analgesia (PCA) in the treatment
      of postoperative pain is well documented. An alternative to electrical systems is
      the disposable pump, which is cost effective. The aim of this study was to prove
      the efficiency and safety of PCA disposable pumps. Eighty patients (45 men, 35
      women, mean age 50 +/- 16 years) were included and received single-use PCA pumps
      (Vygon Medical Products, Aachen, Germany) for postoperative pain control. A
      sufficient reduction in pain levels, measured by the Verbal Rating scale (VRS),
      was achieved in nearly all patients. For the first application, a single bolus of
      7.0 +/- 2 mg piritramide (Dipidolor) was needed, the mean of treatment time was
      56 +/- 31 h. We had two dropouts because of non-compliance, two patients felt
      dizzy, and one patient felt nauseous. Further side-effects were observed during
      treatment. Our study led us concluded that PCA therapy with mechanical,
      disposable pumps is a safe and efficient treatment for postoperative pain. Such a
      concept can be introduced without an "Acute Pain Service" if the staff are well
      trained.

PMID- 9782409
TI  - [Corrective arthrodesis in isolated post-traumatic malalignment of the subtalar
      joint].
AB  - Between 1990 and 1995, 27 patients with posttraumatic disorders of the subtalar
      joint were treated by correcting fusion. Preoperatively 24 patients (88.89%)
      suffered from pain; 15 (55.56%) had a walking range below 100 m. Seven patients
      were unable to work in their original profession. After an average period of
      13.85 months postoperatively the patients were examined again. At this time 18
      (66.67%) had no or minimal pain; 19 (70.37%) had no claudication. According to
      the score of Angus and Skuginna, in 81.48% of patients the result of the
      correcting arthrodesis was successful; according to Kitaoka's clinical rating
      system for ankle-hindfoot, midfoot, hallux and lesser toes, the average
      postoperative score was 75.8 points.

PMID- 9782410
TI  - [The infected arterial stent].
AB  - Vascular infections after percutaneous endovascular procedures are rare. We
      report a case of bacterial arteritis following PTA and stent implantation into an
      iliac artery. It was complicated by septic embolization, ipsilateral empyema of
      the knee joint and formation of an infected false aneurysm. Contamination of the
      stent with Staphylococcus aureus is likely to be the cause. The treatment
      included resection of the infected arterial segment, removal of the stent, and
      autologous reconstruction.

PMID- 9782411
TI  - [Haemosuccus pancreaticus as a rare initial manifestation of chronic
      pancreatitis].
AB  - Haemosuccus pancreaticus is an unfrequent but known cause of an upper
      gastrointestinal bleeding. Pathogenesis of spontaneous severe hemorrhage of the
      pancreatic duct includes chronic pancreatitis generated pseudocysts or aneurysms
      of the visceral arteries. We present two cases of severe spontaneous
      gastrointestinal bleeding as a first manifestation of chronic pancreatitis, in
      which the diagnosis chronic pancreatitis was not known and the patients denied
      any gastrointestinal symptoms in their medical history at the time of hemorrhage.

PMID- 9782412
TI  - [Secondary ulcer perforation after endoscopic hemostasis with fibrin glue].
AB  - Emergency treatment of bleeding ulcer of the duodenum is endoscopy and endoscopic
      blood-staunching. In high-risk patients with Forrest Ia lesions or ulcers with
      visible vessel (Forrest IIa) endoscopic follow-up or early elective operation is
      required. Fibrin sealing can improve the results of endoscopic injection therapy
      for bleeding ulcer. Nevertheless, severe complications such as secondary
      perforation of the fibrin clot or recurrent bleeding can occur. Identification of
      high-risk patients and complications requires close monitoring and attention. A
      case of a secondary perforation of a bleeding ulcer of the duodenum after fibrin
      sealing is reported.

PMID- 9782414
TI  - [Dialysis shunt surgery].

PMID- 9782413
TI  - [Duodeno-caval fistula: a rare cause of upper gastrointestinal hemorrhage].
AB  - Non-traumatic duodenocaval fistulae are rare, but may be the source of massive
      gastrointestional bleeding with associated fever and sepsis. These fistulae
      result from penetrating duodenal peptic ulcers or right nephrectomy and
      subsequent radiation to the upper abdomen. The outcome depends on early diagnosis
      and surgery before a potentially fatal hemorrhage occurs. The therapy of choice
      includes closure of the fistula and repair of the duodenum and inferior vena
      cava. We describe the seventh case with radiogenic duodenal ulcer.
      Gastrointestinal bleeding occurred 10 years after radical nephrectomy and
      radiation (60 Gy). The patient survived following partial pancreatoduodenectomy
      (Whipple).

PMID- 9782415
TI  - Managing asthmatic airway inflammation: what is the role of expired nitric oxide
      measurement?

PMID- 9782416
TI  - Nitric oxide inhalation therapy for newborn infants.
AB  - Binding of NO to heavy metal-containing proteins probably accounts for many of
      its physiologic actions. NO inhalation is a promising new treatment for various
      disorders of neonates. The therapy is most likely to benefit premature neonates
      who are hypoxemic despite breathing pure oxygen and those who suffer from
      impaired carbon dioxide elimination. Newborn infants who have congenital heart
      disease may benefit from inhaled NO therapy if their disease involves some form
      of pulmonary venous hypertension or if they have recently undergone surgery
      involving cardiopulmonary bypass grafting. The use of NO in infants with PPHN
      might obviate the need for ECMO or other invasive treatment methods. Neonates
      with CDH seem likely to benefit marginally from NO therapy. Minimizing the
      toxicities of NO inhalation therapy requires that the physicians understand the
      nuances of infant care. The therapeutic value of increasing carbon dioxide
      elimination with NO inhalation warrants further investigation.

PMID- 9782417
TI  - [Spontaneous perimesencephalic subarachnoid hemorrhage (PMH). A disease category
      with good prognosis?].
AB  - Perimesencephalic subarachnoidal haemorrhage (PMH) is characterized by a typical
      blood distribution pattern in the basal cysterns in the CAT, missing evidence of
      an aneurysm in the panangiogram, a mild clinical course and a very positive
      prognosis. Between 1990 and 1995, 108 inpatients with non-traumatic
      subarachnoidal haemorrhage were treated in our clinic. Within this group 14
      patients (13%) were identified retrospectively with a perimesencephalic
      haemorrhage distribution pattern in the CAT and a negative panangiogram. These
      patients experienced a mild clinical course with excellent outcome without
      rebleeding during the observation period of 2 to 50 months. All patients were
      fully able to work, and only two patients complained of frequent headaches. The
      mild clinical course, the negative panangiogram as well as the extremely positive
      outcome confirm the hypothesis of of a benign subgroup of non-traumatic
      subarachnoidal haemorrhages.

PMID- 9782418
TI  - [Schizophrenia and violence: epidemiological, forensic and clinical aspects].
AB  - Recent studies confirm a significantly (several times, in fact) increased risk
      for schizophrenics to commit severely violent acts compared to the general
      population. Violent acts of minor degree and threats not followed by forensic
      detention are even much more common. Data on prevalence depend on study
      conditions, sample selection, and outcome definitions of violence. In psychiatric
      hospitals, too, violent and threatening behaviour seems to occur most frequently
      in schizophrenic patients. However, in this respect findings are inconsistent and
      display considerable variations across different countries and times (with
      increasing rates reported within the last decade). Additional risk indicators
      beside the diagnosis of schizophrenia are male gender, comorbidity with
      personality disorders, substance abuse, lack of adequate treatment and increasing
      social disintegration due to an unfavourable course of the illness. The violence
      risk does not seem to decrease with increasing age in contrast to the general
      population. Beyond these sociodemographic data and variables related to treatment
      and course of illness, psychopathological causes of violence are less evident.
      Even imperative hallucinations are not clearly associated with violence:
      systematic delusions are associated with severe violent acts, but not with the
      much more frequent violent acts of minor degree. Most probably, the total of
      psychopathological symptomatology is associated with the proneness to aggressive
      behaviour. Neuropsychological and biological findings are also inconsistent.

PMID- 9782419
TI  - [Psychiatric contribution to the debate on films of the silent movie era in
      Germany].
AB  - Literary writers and scientists of various disciplines have contributed to
      debates about the silent movie in the 10s and 20s in Germany, leading to basic
      insights into the structure and effects of the new film medium. Psychiatric
      authors of the documented period have elaborated propositions towards a theory of
      film perception and analyses of different possibly nocuous film effects. The
      hypothesis of a causal effect of the film medium on violence and the notion of a
      transmission of suicidal behaviour by fictitious film models are still
      controversially discussed.

PMID- 9782420
TI  - [German version of the Snaith-Hamilton-Pleasure Scale (SHAPS-D). Anhedonia in
      schizophrenic and depressive patients].
AB  - The Snaith-Hamilton-Pleasure-Scale (SHAPS), introduced in English in 1995,
      assesses self-reported anhedonia in psychiatric patients. It has proven
      psychometric properties and advantages in applicability compared to other
      instruments assessing anhedonia. This study presents results of a systematic
      transcultural protocol translating the SHAPS into German (SHAPS-D). Quality of
      translation was confirmed on the one hand by bilingual reviewers with regard to
      equivalence in content and tone. On the other hand stable results were found in a
      test-retest-design crossing the English and German version with bilingual
      persons. SHAPS-D was obtained from schizophrenic (n = 50) and depressive (n = 33)
      patients and from healthy controls (n = 67). Results on applicability, internal
      consistency and relationship to depression, subjective quality of life, well
      being as well as psychopathology indicate that the SHAPS-D is a useful and
      promising instrument in assessing anhedonia.

PMID- 9782421
TI  - [Anticonvulsant combination therapy: rational concepts versus real
      effectiveness].
AB  - Primary drug treatment of epilepsies is usually a monotherapy with an
      antiepileptic drug. This procedure causes less side effects as polytherapy and
      probably shows the same efficacy. Two third of patients with focal epilepsies are
      sufficiently treated with a single antiepileptic drug: 60% of patients with Grand
      mal and 22-30% of patients with complex focal seizures remain seizures free. An
      alternative monotherapy will suppress seizures in another 30% of patients. With
      polytherapy this is achieved in only 12% of the remaining patients, furthermore,
      side effects increase in polytherapy. Generalized epilepsies are usually treated
      with valproate monotherapy. Patients remain seizure free from absence in 60-90%,
      from myoclonic-impulsive seizures in 75-97% and from Grand mal in about 85%.
      Alternative monotherapy is less common because of the limited efficacy and
      possible side effects of drugs: ethosuximide does not control Grand mal and
      phenobarbitone may cause sedation. Thus, polytherapy is commonly initiated when
      monotherapy fails to control seizures (lamotrigine is often chosen as
      comedication). Rational polypharmacy is a term suggesting rational concepts in
      planning antiepileptic polytherapy leading to a superior anticonvulsant effect.
      However, this consideration is not based on or supported by clinical data. Yet, a
      combination of drugs which have no or little pharmacokinetic interactions seems
      to be a clinically relevant recommendation. Thus, newly developed drugs such as
      vigabatrin, lamotrigine or gabapentin are more frequently used as comedication
      with standard antiepileptic drugs.

PMID- 9782423
TI  - Influence of optic disc size on the sensitivity of the Heidelberg Retina
      Tomograph.
AB  - PURPOSE: The aim of this study was to evaluate the influence of optic disc size
      on the ability of variables generated by the Heidelberg Retina Tomograph,
      software version 1.11, to distinguish glaucoma patients from normals in a cross
      sectional study. PATIENTS AND METHODS: For evaluation of the optic disc with the
      Heidelberg Retina Tomograph, eyes of 87 normals and 61 glaucoma patients were
      selected. Disc area, volume above reference, rim area, cup area, cup volume,
      third moment in contour and the mean retinal nerve fibre layer thickness at the
      border of the optic disc were selected for evaluation. The sensitivity at 80%
      specificity of these variables was calculated under three conditions: (1) no
      correction for disc size; (2) calculation in the following disc size ranges:
      class I (1.0-2.0 mm2), class II (2.0-2.5 mm2), class III (2.5-3.15 mm2) and class
      IV (3.15-5.0 mm2); (3) calculation globally, taking into account the different
      disc sizes of the four classes. RESULTS: Neuroretinal rim area, cup area and
      volume, third moment and nerve fibre layer thickness were significantly and
      positively correlated with optic disc size in normals. Neuroretinal rim volume
      measurements were statistically independent of optic disc size. Sensitivity was
      lowest when the size of the optic disc was not considered. Sensitivity increased
      when evaluated in four optic disc size classes. With growing optic disc size
      sensitivity of the retinal nerve fibre layer increased and third moment value
      decreased. Cup volume and area had their lowest sensitivity for large optic
      discs. The area of the neuroretinal rim was the only variable which showed
      similar sensitivity values under all three conditions. CONCLUSIONS: The
      sensitivities of HRT variables varied with optic disc size. Evaluation of their
      sensitivity requires the definition of optic disc classes or statistical
      correction for the size of the optic disc.

PMID- 9782422
TI  - [Quantitative assessment of brain morphology with CT in agoraphobia].
AB  - This CT study was designed to assess brain morphology in agoraphobia. 21 patients
      and 21 normal control subjects matched in age and sex were investigated. Frontal
      and parietooccipital cortex, temporal cortex, lateral ventricles and third
      ventricle were evaluated by qualitative assessment on a 3-point scale (normal,
      questionable, abnormal). Patients showed significant bilateral enlargement of
      prefrontal cortical cerebrospinal fluid (CSF) spaces (p < .05). The rating
      "abnormal" was given to none (0%) of the normal controls, but to 6 (28.6%) of the
      patients in the left hemisphere, and to 4 patients (19%) in the right hemisphere,
      respectively. No qualitative differences were seen in the temporal cortex,
      lateral ventricles and third ventricle. These findings support the hypothesis
      that alterations in brain morphology are involved in the etiology of agoraphobia.
      The lack of a correlation between CSF enlargement and duration of illness
      suggests that prefrontal CSF enlargement is a neurobiological vulnerability
      marker in agoraphobia.

PMID- 9782424
TI  - Bilateral periocular actinic granuloma in a patient with renal failure: a
      clinicopathologic study.
AB  - PURPOSE: We report a 50-year-old man with end-stage renal disease who has
      developed bilateral inner and outer canthal nodules. METHODS: The nodules were
      excised, fixed in 10% formalin and 2.5% glutaraldehyde, and processed for light
      and electron microscopy, respectively. RESULTS: Histological examination showed
      elastotic changes with associated granulomatous inflammation. The granulomatous
      reaction was centered around elastotic fibers, and some giant cells engulfed the
      fibers. Areas of dystrophic calcification were identified. A diagnosis of actinic
      granuloma was made. The differential diagnosis and histopathology of actinic
      granuloma, i.e. granuloma annulare, rheumatoid nodule, and necrobiotic
      xanthogranuloma, are discussed. CONCLUSION: This case of an actinic granuloma
      originating in the sun-damaged periocular skin provides further evidence that
      elastotic degeneration may be associated with a giant cell reaction. It is,
      however, unclear which antigens are responsible for initiating the granulomatous
      response and whether elastotic material on its own can elicit a granulomatous
      reaction.

PMID- 9782425
TI  - Adjunctive mitomycin C in primary trabeculectomy in young adults: a long-term
      study of case-matched young patients.
AB  - OBJECTIVE: The purpose of this study was to determine the efficacy of initial
      mitomycin C (MMC)-augmented trabeculectomy for uncomplicated glaucoma in young
      patients. METHODS: A retrospective chart review was performed on all glaucoma
      patients aged between 15 and 40 years without previous surgery that underwent
      initial trabeculectomy with MMC between 1988 and 1995 at the University Eye
      Hospital of Cologne. Success (survival) was defined as an intraocular pressure
      (IOP) of 21 mmHg or lower, with (qualified success) or without (complete success)
      glaucoma medications. The results were compared with a case-matched control group
      that did not receive antiproliferative therapy. RESULTS: Eleven eyes of 11
      patients fulfilled the inclusion criteria of initial MMC-augmented
      trabeculectomy. Using cumulative life-table analysis the success rate was 91% at
      1 year and 73% at 5 years for the control group. For the MMC group the success
      rate was 91% at 1 year and 5 years, respectively. At final visit, mean IOP was
      significantly (P < 0.001) lower for the MMC group (13.3 +/- 3.9 mmHg) than for
      controls (18.0 +/- 1.3 mmHg). Significant differences were also found in the
      complication rate: complications associated with excessive aqueous
      overfiltration, such as shallow anterior chamber (36%), choroidal detachment
      (45%) and persistent hypotony (27%), featured particularly in the MMC group.
      Conversely, scarring of the filtering bleb (18%) and Tenon's cysts (18%) were
      observed exclusively in control eyes. CONCLUSION: The present results suggest
      that initial MMC trabeculectomy for uncomplicated glaucoma in young patients
      significantly reduces IOP and number of adjunctive medications, postoperatively,
      albeit at the price of a high incidence of hypotony.

PMID- 9782426
TI  - Ocular symptoms in association with antiphospholipid antibodies.
AB  - OBJECTIVE: To describe the clinical and serologic findings of 50 antiphospholipid
      antibody (APA)-positive patients within a retrospective study. METHODS:
      Measurement of visual acuity, slit-lamp biomicroscopy, tonometry, fundus
      examination and perimetry. Laboratory tests were performed for detection of APA
      against thromboplastin and cardiolipin. Antinuclear antibodies (ANA), antibodies
      to dsDNA, antithyroidal and antiparietal antibodies were also tested. RESULTS: A
      combination of both transient and permanent visual disturbances was noticed in
      more than half of the patients. Transient visual disturbances included transient
      blurred vision, partial defects of the visual fields and amaurosis fugax. The
      most frequent permanent abnormalities were optic atrophy in 20 patients, due to
      AION in 9 cases, and disturbances of the choroidal circulation in 17 patients.
      Fourty-six patients had positive levels of thromboplastin APA; cardiolipin APA
      were found to be increased in 36 patients. CONCLUSIONS: We did not find a clear
      correlation between APA activity or the immunoglobulin classes in the individual
      and the severity of the ocular disease. The benefit from a therapy with the
      antiplatelet agent acetylsalicylic acid was evident in a reduction of the
      patients' transient visual disturbances and, in most cases, no further
      progression of permanent visual field defects was observed.

PMID- 9782428
TI  - Functional anatomy of the human efferent tear ducts: a new theory of tear outflow
      mechanism.
AB  - BACKGROUND: The mechanism of lacrimal drainage under physiological conditions is
      controversial. The aim of this study was to analyze the three-dimensional
      architecture of human efferent tear ducts from functional and clinical points of
      view. A new theory of tear outflow is discussed. METHODS: Thirty-two prepared
      lacrimal systems of adults were examined by histological, immunohistochemical and
      scanning electron microscopic techniques. RESULTS: The wall of the lacrimal sac
      is made up of collagen bundles, elastic and reticular fibers arranged in a
      helical pattern. Wide luminal vascular plexus are embedded in this helical system
      and connected to the cavernous tissue of the inferior turbinate in the region of
      Hasner's valve. Immunohistochemical analysis showed evidence of type I and type
      III collagen as well as chondroitin 4- and 6-sulfate. CONCLUSION: With blinking,
      the lacrimal part of the orbicularis muscle contracts. The fornix of the sac
      moves in a cranial-lateral direction. Thus the lacrimal sac distends and may be
      "wrung out" due to its medial attachment and helically arranged fibrillar
      structures. The vascular plexus may play an important role in the absorption and
      drainage of lacrimal fluid.

PMID- 9782427
TI  - Tamoxifen retinopathy: does it really exist?
AB  - BACKGROUND: Tamoxifen retinopathy is known to be an adverse effect of high-dose
      tamoxifen treatment. Evidence of ocular toxicity at lower doses is less
      convincing: the aim of this study was to assess the prevalence of the above
      mentioned retinopathy in a population treated with low-dose tamoxifen. METHODS:
      One hundred and twenty-nine women treated with low-dose tamoxifen (20 mg/day)
      were examined. Visual acuity measurement, slit-lamp biomicroscopy and fundus
      examination were performed. Patients were reexamined after 6-12 months. RESULTS:
      Refractile retinal opacities, similar to those previously described as tamoxifen
      retinopathy, were observed in four patients (prevalence 3.1%; mean duration of
      therapy 806 days). None of them revealed corneal opacities, papillary and/or
      macular edema, or visual impairment. The ophthalmoscopic aspect did not change
      after a mean follow-up of 215 days, although one of these patients had
      interrupted tamoxifen intake. Statistical analysis (Student's t-test) did not
      reveal any difference between patients with and those without refractile retinal
      opacities as far as age, treatment duration and ERG values were concerned. An
      early hyperfluorescence, reminescent of cuticular drusen, was demonstrated by
      fluorescein angiography in all four cases. CONCLUSIONS: The present study would
      seem to confirm that low-dose tamoxifen may induce retinal toxicity in a low
      proportion of patients, but we cannot be certain that the refractile retinal
      opacities observed are really caused by tamoxifen, as differentiation from age
      related macular degeneration with cuticular drusen appears nearly impossible.

PMID- 9782430
TI  - Retinal degeneration induced by N-methyl-N-nitrosourea in Syrian golden hamsters.
AB  - BACKGROUND: The sequential retinal changes in Syrian golden hamsters induced by N
      methyl-N-nitrosourea (MNU) have not been studied. METHODS: Female hamsters
      received a single intraperitoneal injection of 90 mg/kg MNU at 50 days of age,
      and the retina was examined light and electron microscopically,
      immunohistochemically and by the TdT-mediated dUTP-digoxigenin nick end labeling
      (TUNEL) method until 20 weeks after the treatment. RESULTS: The retinal changes
      were as follows: (1) Photoreceptor apoptosis occurred 1 day after the treatment
      and resulted in photoreceptor loss at day 7. During the degeneration, Muller cell
      proliferation was conspicuous at day 5. (2) After the photoreceptor cell loss,
      migration of the pigment epithelial cells in all layers of the retina which were
      in contact with blood vessels occurred. Due to the Muller cell proliferation,
      gliosis was prominent at the later stage. CONCLUSIONS: The MNU injection caused
      photoreceptor apoptosis followed by pigment epithelial cell migration around the
      blood vessels, accompanied by gliosis. The primary event and the course of this
      disease closely resemble those of retinitis pigmentosa in humans.

PMID- 9782429
TI  - Glycosaminoglycan and collagen distribution in the developing human vitreous.
AB  - BACKGROUND: We determined the distribution of glycosaminoglycans and collagens in
      the developing human vitreous. METHODS: Eighty human eyes from 5 gestational
      weeks to 2 postnatal years of age were used. Glycosaminoglycan components were
      determined by enzyme digestion with hyaluronidase or chondroitinase AC and ABC
      and immunohistochemistry for chondroitin, chondroitin-4-sulfate, chondroitin-6
      sulfate, and dermatan sulfate. Collagen distribution was determined by
      immunohistochemistry for types I, II, and III collagens. RESULTS: Enzyme
      digestion showed that throughout development hyaluronic acid is the main
      glycosaminoglycan in the vitreous and in the extraocular space at 5-7 gestational
      weeks. Both areas were filled with mesenchymal cells. Immunohistochemistry showed
      chondroitin-6-sulfate in the vitreous between 6 and 40 gestational weeks, and
      chondroitin-4-sulfate between 12 and 40 gestational weeks. Hyaluronic acid and
      chondroitin sulfate appeared in the retina and around the hyaloid vessels at 12
      40 weeks. Immunohistochemistry showed type III collagen in the vitreous and
      around the mesenchymal cells at 5-7 weeks that was replaced by type II collagen
      after 8 weeks. CONCLUSIONS: Hyaluronic acid is the major glycosaminoglycan in the
      vitreous throughout development, except for the transient appearance of
      chondroitin sulfate at 6-40 gestational weeks. Type III is the main collagen in
      the early developing vitreous that converts to type II collagen at 8 weeks. The
      primary and secondary vitreous has the same components as these macromolecules.
      These vitreous glycosamino-glycans and collagens seem to be produced by
      mesenchymal cells at an early stage and by the retina and hyaloid vessels during
      middle and late development.

PMID- 9782431
TI  - Observation of ultrastructural changes in cultured retinal pigment epithelium
      following exposure to blue light.
AB  - BACKGROUND: The retina can be damaged by light even when levels of energy are
      well below the threshold for thermal damage, and the experimental damage of the
      retinal pigment epithelium (RPE) may be induced more easily by blue light than by
      longer wavelengths of visible light. The present study demonstrates the
      ultrastructural damage produced by exposure to blue light in cultured RPE.
      METHODS: Long-Evans rats were enucleated 8-10 days after birth for primary
      culture. One week after seeding, the monolayer culture of RPE cells was exposed
      to a cool blue light (wavelength = 440 +/- 10 nm) for 36 h (12 h/day, 3 days) at
      2.0 mW/cm2. Transmission electron microscopy was used to compare the exposed RPE
      with the control. The entire experiment was repeated 3 times independently.
      RESULTS: The cytoplasm of the exposed RPE exhibited degenerative changes, such as
      large whorls of membrane, lamellar whorls and whorled inclusions. CONCLUSION: The
      RPE cells can be damaged directly by blue light after excluding the possible
      influence of phagosomes. This primary culture of RPE can also serve as an in
      vitro model for the study of light damage to the RPE.

PMID- 9782432
TI  - Growth factors in cultured pterygium fibroblasts: immunohistochemical and ELISA
      analysis.
AB  - BACKGROUND: In order to study growth factors in the pathogenesis and recurrence
      of pterygium, we grew pterygium tissues in culture and compared fibroblasts from
      primary and from recurrent pterygia with reference to the fibroangiogenic growth
      factors basic fibroblast growth factor (b-FGF), platelet-derived growth factor
      (PDGF), transforming growth factor beta (TGF-beta) and tumor necrosis factor
      alpha (TNF-alpha). METHODS: We used indirect immunohistochemical procedures
      against human b-FGF, PDGF, TGF-beta and TNF-alpha. As controls, we used cultured
      normal human conjunctival fibroblasts. A serum-free conditioned medium (CM) from
      confluent fibroblasts derived from primary and recurrent explants was assessed by
      enzyme-linked immunosorbent assay to determine the level of the above-mentioned
      growth factors. RESULTS: Immunoreactivity of b-FGF was stronger in recurrent than
      in primary pterygium fibroblasts. PDGF immunolabeling was stronger in primary
      than in recurrent pterygium fibroblasts. TGF-beta and TNF-alpha immunolabeling
      was weak in both pterygia. All these growth factors were very sparse in normal
      conjunctival fibroblasts. Basic-FGF and TGF-beta 1 were found in the CM from both
      primary and recurrent pterygium, while PDGF and TNF-alpha were not detectable.
      CONCLUSION: The strong immunoreactivity and the release of b-FGF in cultured
      fibroblasts of recurrent pterygia suggest that fibroblasts may play an important
      role in the recurrence of pterygium.

PMID- 9782433
TI  - Temporary vitreous gas tamponade by perfluoromethylcyclopentane.
AB  - Using perfluoromethylcyclopentane (FMCP; US patent no. 5,441,989, granted 1995)
      we have developed a new vitreous gas tamponade in a rabbit model that allows
      complete filling of the vitreous cavity without vitrectomy and without a
      significant increase in intraocular pressure. In humans this procedure would
      allow the blockage of inferior and posterior retinal holes without special
      positioning of the patient. Perfluoromethylcyclopentane (FMCP), a liquid
      perfluorocarbon with a boiling point slightly above body temperature, is injected
      in minute volumes into the vitreous cavity, where it vaporizes, thereby filling a
      gas volume approximately 500 times its liquid volume. FMCP was injected into the
      midvitreous in six rabbits (six eyes). After 2-3 days a complete gas tamponade
      was achieved in three eyes. Two eyes showed 75-90% filling, and one eye was
      filled only 50% with gas. Intraocular pressure was highest in the completely
      filled eyes, ranging from 26.6 to 38.8 mmHg. In all eyes the maximum expansion of
      the gas bubble lasted 2 weeks. One eye developed a retinal detachment. All eyes
      showed transient subcapsular cataracts. The results of this study showed that
      intravitreal injection of FMCP, a new perfluorocarbon liquid, results in a
      complete gas tamponade of the vitreous cavity which lasts 2 weeks without severe
      intraocular pressure rise and without vitrectomy. This procedure will be
      especially useful for eyes that have retinal detachment from inferior or
      posterior retinal holes. Injection of a conventional gas such as SF6 or C3F8
      usually does not block retinal holes in inferior or posterior locations without
      tedious positioning and risk of (transient) glaucoma. Since the mechanism of
      transition of FMCP from liquid to gas in the vitreous is poorly understood, we
      are currently studying FMCP vaporization in an in vitro eye model.

PMID- 9782434
TI  - Hemorrhagic fever (Puumala virus infection) with ocular involvement.
AB  - BACKGROUND: Puumala virus infection (nephropathia epidemica) is a disease in the
      group of hemorrhagic fevers with renal syndrome causing ocular manifestations,
      e.g. transient myopia and changes in intraocular pressure. PATIENT AND METHODS:
      Comprehensive and repeated ophthalmic examinations of a previously healthy 35
      year-old woman with acute Puumala virus infection were performed. Special
      attention was paid to ophthalmic A-scan ultrasound measurements and simultaneous
      blood chemistry tests. RESULTS: The ocular manifestations of this patient's
      illness included transient myopia, low intraocular pressure, conjunctival
      hemorrhages and changes of intraocular dimensions. There was forward movement of
      the anterior diaphragm and thickening of the crystalline lens, which occurred
      simultaneously with prominent fluctuations in the electrolyte balance, especially
      potassium. CONCLUSIONS: The observed changes in intraocular dimensions may have
      been caused by simultaneous fluctuations in electrolyte and osmotic balance,
      which could explain the myopic shift. The symmetry of the ocular measurements
      implied a systemic infection as the underlying reason for the ophthalmic symptoms
      and signs.

PMID- 9782436
TI  - Posterior chamber intraocular lens use in children.
AB  - PURPOSE: The authors report on the efficacy of intraocular lens implantation
      during pediatric cataract surgery and the results of a consecutive series of
      intraocular lens implantation in children. METHODS: Twenty-one children underwent
      implantation of intraocular lenses in 23 eyes. Twenty-one surgeries were primary
      implantation immediately following anterior lensectomy. Two surgeries were
      secondary implantations. Primary posterior capsulectomy was performed in 18 of 21
      primary implantations. All but two eyes underwent a primary anterior vitrectomy.
      Topical prednisolone acetate was administered in all cases. Oral prednisone was
      administered in 17 of 23 cases. Pre- and postoperative visual acuity, cycloplegic
      refraction, and postoperative complications related to inflammation such as
      intraocular lens (IOL) capture, IOL decentration, and posterior capsule
      opacification were examined. RESULTS: Eighteen of 23 eyes have achieved a visual
      acuity of 20/40 or better. None of the cases in which oral prednisone was used
      developed complications related to postoperative inflammation. One of the six
      cases (17%) in which oral prednisone was not used developed such complications.
      CONCLUSION: Intracular lens implantation accompanied by primary posterior
      capsulectomy, anterior vitrectomy, and management of postoperative inflammation
      appears to provide appropriate and safe optical rehabilitation in children.

PMID- 9782435
TI  - Lepromatous uveitis diagnosed by iris biopsy.
AB  - Ocular leprosy is rarely seen in developed countries. We report the long-term
      follow-up of a patient with bilateral uveitis, glaucoma, and keratitis. Skin,
      iris and aqueous humor biopsies disclosed abundant Wade-Fite-positive organisms
      consistent with Mycobacterium leprae. Leprosy must be considered in the
      differential diagnosis of keratitis and uveitis.

PMID- 9782437
TI  - A comparison of prophylactic ondansetron hydrochloride and droperidol for
      strabismus repair in adults.
AB  - BACKGROUND: Prophylactic administration of an antiemetic is a common procedure
      for patients undergoing strabismus surgery. Droperidol and ondansetron
      hydrochloride are commonly used antiemetics. This study compared the rates of
      postoperative nausea and vomiting (PONV) in adult patients undergoing strabismus
      surgery with prophylactically administered Droperidol or ondansetron
      hydrochloride. METHODS: A double-masked, randomized, prospective study was
      conducted comparing droperidol with ondansetron hydrochloride when administered
      prophylactically to adults undergoing strabismus surgery. RESULTS: Forty-five
      patients entered the study with a mean age of 30 years. Twenty percent of
      patients had nausea immediately postoperatively and 37% had nausea before
      discharge with no significant differences between groups. Overall rate of emesis,
      time in the recovery room, and time to discharge was not significantly different
      between the droperidol and ondansetron hydrochloride group. CONCLUSION: No real
      differences in the ability to prevent PONV between the two medications were found
      in this study.

PMID- 9782438
TI  - Deletion 3q in two patients with blepharophimosis-ptosis-epicanthus inversus
      syndrome (BPES).
AB  - BACKGROUND: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is an
      autosomal dominant condition mapped to chromosome 3q23. There are several reports
      of chromosomal abnormalities involving this region with a resultant phenotype
      that includes BPES. METHOD: We reassessed two unrelated boys ages 3 and 5 with
      BPES and associated nonocular abnormalities. Karyotype, which had been previously
      reported as normal, was repeated using high-resolution banding techniques, to
      look specifically at 3q23. Clinical findings were tabulated and compared with
      previously reported cases. RESULTS: Both patients proved to have interstitial
      deletions of chromosome 3, the first involving bands q22.2q25.1 and the second
      q22.2q24. The first patient exhibited prenatal and postnatal growth retardation,
      with global developmental delay, while the second patient had normal growth and
      development except for speech delay. Both had dysmorphic facies with BPES, flat
      philtrum, a thin upper lip, and small chin. In addition, the first boy had an
      inguinal hernia and hypospadius; the second boy had abnormal auricles and
      metatarsus adductus. The eight cases of interstitial deletions of 3q2 and six
      rearrangements involving this region have a remarkably similar phenotype.
      CONCLUSIONS: Deletion of 3q23 is a recognizable contiguous gene syndrome.
      Microdeletions of 3q23 should be ruled out in any sporadic case of BPES
      especially if there are associated nonocular abnormalities.

PMID- 9782439
TI  - Tucking the inferior oblique muscle into Tenon's capsule following myectomy.
AB  - PURPOSE: Myectomy of the inferior oblique muscle is a common procedure used to
      correct overaction of this muscle. Previous descriptions of the surgery have not
      discussed how the surgeon should handle the proximal muscle stump following
      myectomy. This study examined the effectiveness of inferior oblique muscle
      myectomy with tucking of the muscle into Tenon's capsule for treatment of
      inferior oblique muscle overaction. METHODS: The procedure was studied
      prospectively in 22 patients who underwent 32 inferior oblique muscle myectomies.
      In 18 patients, the intraoperative behavior of the inferior oblique muscle was
      recorded. Complete ocular motility examinations were performed before and after
      surgery. Success was defined as the elimination of inferior oblique muscle
      overaction and the elimination of hypertropia secondary to persistent ipsilateral
      inferior oblique muscle overaction in primary gaze. RESULTS: The surgery
      corrected inferior oblique muscle overaction in 94% of eyes. Hypertropia
      secondary to persistent ipsilateral inferior oblique muscle overaction was
      eliminated in 92% of patients. There was no correlation between outcome and the
      intraoperative behavior of the inferior oblique muscle. CONCLUSION: Tucking of
      the inferior oblique muscle stump into Tenon's capsule is recommended following
      inferior oblique myectomy. This procedure is safe and effective for correcting
      inferior oblique muscle overaction.

PMID- 9782440
TI  - Congenital cataract surgery in children with cataract as an isolated defect and
      in children with a systemic syndrome: a comparative study.
AB  - PURPOSE: To compare visual acuity outcome in two groups of children who underwent
      congenital cataract surgery. The first group is one in which an isolated cataract
      occurred; the second group is one in which cataract occurred in conjunction with
      a systemic disease. METHODS: A review of 46 charts: 36 children (50 eyes) with
      congenital cataract as an isolated defect, and 10 children (16 eyes) with
      cataract as part of a systemic disease. RESULTS: One third of the eyes with
      isolated cataract had postoperative visual acuity better than 6/12, although none
      of the patients in the syndrome group had visual acuity better than 6/12. This
      difference was statistically significant (p = 0.01). Of the various ocular
      pathologies associated with congenital cataract, only nystagmus was found to be
      more prevalent in the syndrome group (40%) as compared with the isolated cataract
      group (11%) (p = 0.05). Surgery was performed during the first 2 years of life in
      54% of the eyes in the isolated cataract group, and in 87% of the eyes in the
      syndrome group (p = 0.01). There was no difference in the prevalence of the
      postoperative complications between the two groups. CONCLUSION: Children who
      underwent congenital cataract surgery developed poorer visual acuity if the
      cataract was a part of a systemic disease as compared with children without a
      systemic syndrome.

PMID- 9782442
TI  - Ocular complications of cloverleaf skull syndrome.

PMID- 9782441
TI  - Multiple evanescent white-dot syndrome in a 10-year-old child.

PMID- 9782443
TI  - Congenital absence of the nasolacrimal duct.

PMID- 9782444
TI  - Arcachon and cholinergic transmission.
AB  - The cholinergic nature of transmission at the electromotor synapse of Torpedo
      marmorata was established at Arcachon in 1939 by Feldberg, Fessard and
      Nachmansohn (J. Physiol. (Lond.) 97 (1939/1940) 3P-4P) soon after transmission at
      the neuromuscular junction had been shown to be cholinergic. In 1964, after a
      quarter of a century of neglect, workers in Cambridge, then in Paris, Gottingen
      and elsewhere, began to use this system, 500-1000 times richer in cholinergic
      synapses than muscle, for intensive studies of cholinergic transmission at the
      cellular and molecular level.

PMID- 9782445
TI  - Early days in the research to localize skeletal muscle acetylcholinesterases.
AB  - Very early in the study of the mechanism of neuromuscular transmission in
      skeletal muscles, it was clear that the hydrolysis of acetylcholine by muscle
      cholinesterases within the time of the refractory period required a very high
      concentration of the enzyme near the motor terminals. David Nachmansohn and
      George B. Koelle and their collaborators obtained the first biochemical and
      histochemical data consistent with this prediction. Now that the various
      molecular forms of AChE have been satisfactorily described, it is possible to
      analyse the mechanisms by which they are anchored to the structures of the
      neuromuscular junction, and in particular, to the synaptic basal lamina.

PMID- 9782446
TI  - Allosteric nicotinic receptors, human pathologies.
AB  - Nicotinic acetylcholine receptors are ligand-gated ion channels present in muscle
      and brain. These allosteric oligomers may exist in several conformational states
      which include a resting state, an open-channel state, and a desensitized
      refractory state. Recent work has shown that point mutations in the nicotinic
      receptor may, altogether, abolish desensitization, increase apparent affinity for
      agonists and convert the effect of a competitive antagonist into an agonist
      response. These pleiotropic effects are interpreted in terms of the allosteric
      model. This paper reviews recent evidence that such mutations occur spontaneously
      in humans and may cause diseases such as congenital myasthenia or familial
      frontal lobe epilepsy. In addition, nicotinic receptors are involved in tobacco
      smoking. Accumulating evidence, including experiments with knock-out animals,
      indicates that addiction to nicotine is linked to the activation of beta 2
      subunit containing nicotinic receptors in the dopaminergic mesolimbic neurons
      which are part of the reward systems in the brain. Current research also
      indicates that nicotinic agonists might serve as therapeutic agents for
      Alzheimer's disease and Tourette's syndrome, as well as for schizophrenia. This
      paper extends and updates a recently published review.

PMID- 9782447
TI  - Dissection of active zones at the neuromuscular junction by EM tomography.
AB  - We used EM tomography to examine the fine structure of the apparently amorphous
      electron dense material that is seen at active zones of axon terminals when
      viewed by conventional 2D electron microscopy. Serial 1-nm optical slices from 3D
      reconstructions of individual thin tissue sections reveal that the material is
      composed of an interconnecting network of elongate components directly linked to
      synaptic vesicles and the presynaptic membrane. Each vesicle at the active zone
      that lies adjacent to the presynaptic plasma membrane has several such
      connections. Information provided by reconstruction data may be useful in
      generating experiments aimed at understanding the mechanisms involved in the
      docking of synaptic vesicles and their exocytosis during synaptic transmission.

PMID- 9782449
TI  - The role of subunit interfaces for the nicotinic acetylcholine receptor's
      allosterism.
AB  - Cross-linking of nicotinic acetylcholine receptors, combined with binding studies
      and patch-clamp electrophysiology, has proven the existence of a 'pre-existing
      equilibrium' of functional states and the functional role of subunit interfaces,
      two key postulates of the allosteric model.

PMID- 9782448
TI  - Toxins selective for subunit interfaces as probes of nicotinic acetylcholine
      receptor structure.
AB  - The pentameric structure of the nicotinic acetylcholine receptor with two of the
      five subunit interfaces serving as ligand binding sites offers an opportunity to
      distinguish features on the surfaces of the subunits and their ligand specificity
      characteristics. This problem has been approached through the study of assembly
      of subunits and binding characteristics of selective peptide toxins. The
      receptor, with its circular order of homologous subunits (alpha gamma alpha delta
      beta), assembles in only one arrangement, and through mutagenesis, the residues
      governing assembly can be ascertained. Selectivity of certain toxins is
      sufficient to readily distinguish between sites at the alpha gamma and alpha
      delta interfaces. By interchanging residues on the gamma and delta subunits, and
      ascertaining how they interact with the alpha-subunit, determinants forming the
      binding sites can be delineated. The alpha-conotoxins, which contain two
      disulfide loops and 12-14 amino acids, show a 10,000-fold preference for the
      alpha delta over the alpha gamma subunit interface with alpha epsilon falling
      between the two. The waglerins, as 22-24 amino acid peptides with a single core
      disulfide loop, show a 2000-fold preference for alpha epsilon over the alpha
      gamma and alpha delta interfaces. Finally, the 6700 Da short alpha-neurotoxin
      from N. mossambica mossambica shows a 10,000-fold preference for the alpha gamma
      and alpha delta interfaces over alpha epsilon. Selective mutagenesis enables one
      to also distinguish alpha-neurotoxin binding at the alpha gamma and alpha delta
      subunits. This information, when coupled with homology modeling of domains and
      site-directed residue modification, reveals important elements of receptor
      structure and conformation.

PMID- 9782450
TI  - Allosteric modulation of neuronal nicotinic acetylcholine receptors.
AB  - The structure-function relationship of the neuronal nicotinic acetylcholine
      receptor is examined in the light of the allosteric concepts. Effects of site
      directed mutagenesis as well as those caused by allosteric effector of the
      physiological and pharmacological receptor properties are discussed.

PMID- 9782451
TI  - Molecular dissection of subunit interfaces in the nicotinic acetylcholine
      receptor.
AB  - Ligand binding sites in the muscle nicotinic acetylcholine receptor are generated
      by pairs of alpha and non-alpha subunits. The non-alpha subunits, gamma, delta
      and epsilon, contribute significantly to overall affinity of agonists and
      antagonists, and confer selectivity of these ligands for the two binding sites.
      By constructing chimeras composed of segments of the various non-alpha subunits
      and determining ligand selectivity, we have identified four loops, well separated
      in the linear sequence, that contribute to the non-alpha portion of the binding
      site. Studies of point mutations in these loops and labeling of engineered
      cysteines show that the peptide backbones of each non-alpha subunit fold into
      similar basic scaffolds. Studies of mutations of the peptide antagonists alpha
      conotoxin M1 and ImI reveal pairs of residues in the binding site and the toxin
      that stabilize the complex.

PMID- 9782453
TI  - Congenital myasthenic syndromes: experiments of nature.
AB  - Congenital myasthenic syndromes (CMS) can arise from presynaptic, synaptic, or
      postsynaptic defects. Recent studies indicate that mutations in the acetylcholine
      receptor (AChR) subunit genes are a common cause of the postsynaptic CMS. The
      mutations, which increase or decrease the response to acetylcholine, are
      experiments of nature that highlight functionally significant domains of the
      AChR.

PMID- 9782452
TI  - Functional determinants by which snake and cone snail toxins block the alpha 7
      neuronal nicotinic acetylcholine receptors.
AB  - Snakes and cone snails produce toxins which block muscular and/or neuronal
      nicotinic acetylcholine receptors (AChRs). This paper mostly focuses on the
      determinants by which a snake long chain curaremimetic toxin and the cone snail
      toxin ImI bind specifically to the alpha 7 neuronal receptor. In both cases, the
      site involves a small turn-like structure constrained by two half-cystines.

PMID- 9782454
TI  - Regulated exocytosis in neurons and neurosecretory cells: structural events and
      expression competence.
AB  - This paper summarizes the contribution of the laboratory first in the development
      of the 'kiss-and-run model' of exocytosis, with its fascinating aspects of
      specificity and rapidity, then in proposing the existence of 'competence factors'
      that appear to govern the appearance of the secretory vesicles and exocytic
      process in neurosecretory cells.

PMID- 9782455
TI  - Acetylcholine release. Reconstitution of the elementary quantal mechanism.
AB  - Choline acetyltransferase and vesicular acetylcholine transporter genes are the
      products of two adjacent genes defining a cholinergic locus. The release
      mechanism is expressed independently of this locus in some cell lines. A
      cholinergic neuron will therefore have to coordinate the expression of release
      with that of the cholinergic locus. Transfection of a plasmid encoding Torpedo
      mediatophore in cells that are unable to release this transmitter endows them
      with a Ca2(+)-dependent and quantal release mechanism. The synchronization of
      mediatophore activation results from a control of calcium microdomains by the
      synaptic vesicles. It is therefore dependent on the proteins that dock vesicles
      close to calcium channels.

PMID- 9782456
TI  - Protein interactions implicated in neurotransmitter release.
AB  - Biochemical evidence indicates that the exocytotic release of neurotransmitters
      involves both evolutionary conserved membrane proteins, the SNAREs, as well as
      ubiquitous cytosolic fusion proteins, NSF and SNAPs. We have analyzed the
      biochemical properties and the physiological effects of these proteins. Our data
      suggest models how NSF, SNAPs and SNAREs may function in neurotransmitter
      exocytosis.

PMID- 9782457
TI  - On the action of botulinum neurotoxins A and E at cholinergic terminals.
AB  - Botulinum neurotoxins type A and E (BoNT/A and /E) are metalloproteases with a
      unique specificity for SNAP-25 (synaptosomal-associated protein of 25 kDa), an
      essential protein component of the neuroexocytotic machinery. It was proposed
      that this specificity is based on the recognition of a nine-residue sequence,
      termed SNARE motif, which is common to the other two SNARE proteins: VAMP
      (vesicle-associated membrane protein) and syntaxin, the only known substrates of
      the other six clostridial neurotoxins. Here we report on recent studies which
      provide evidence for the involvement of the SNARE motif present in SNAP-25 in its
      interaction with BoNT/A and /E by following the kinetics of proteolysis of SNAP
      25 mutants deleted of SNARE motifs. We show that a single copy of the motif is
      sufficient for BoNT/A and /E to recognise SNAP-25. While the copy of the motif
      proximal to the cleavage site is clearly involved in recognition, in its absence,
      other more distant copies of the motif are able to support proteolysis. We also
      report on studies of poisoning human neuromuscular junctions with either BoNT/A
      or BoNT/E and describe the unexpected finding that the time of recovery of
      function after poisoning is much shorter in the case of type E with respect to
      type A intoxication. These data are discussed in terms of the different sites of
      action of the two toxins within SNAP-25.

PMID- 9782458
TI  - Dissociation of the vesicular acetylcholine transporter domains important for
      high-affinity transport recognition, binding of vesamicol and targeting to
      synaptic vesicles.
AB  - Chimeras between the human vesicular acetylcholine transporter (hVAChT) and the
      neuronal isoform of the human vesicular monoamine transporter (hVMAT2) have been
      constructed and stably expressed in a rat pheochromocytoma cell line (PC12) in an
      effort to identify cholinergic-specific domains of VAChT. Examination of the
      transport properties of a chimera in which the N-terminal portion (up to putative
      transmembrane domain II and including the lumenal glycosylated loop) of hVAChT
      was replaced with hVMAT2 sequences (2/V@NheI) revealed that its apparent affinity
      for acetylcholine (ACh) was reduced approximately seven-fold compared to wild
      type. However, the affinity of this chimera for vesamicol did not significantly
      differ from hVAChT. Similarly, the 2/V@NheI chimera retained its preferential
      targeting to the small synaptic-like vesicles found in PC12 cells in agreement
      with our recently reported observations that the synaptic vesicle targeting
      domain resides in the cytoplasmic tail of VAChT.

PMID- 9782459
TI  - The cholinergic locus: ChAT and VAChT genes.
AB  - The gene encoding the vesicular acetylcholine transporter has been localized
      within the first intron of the gene encoding choline acetyltransferase and is in
      the same transcriptional orientation. These two genes, whose products are
      required for the expression of the cholinergic phenotype, could therefore be
      coregulated. The promoters of both genes have been identified. The mechanisms
      that account for the regulation of the expression of both genes are now being
      investigated.

PMID- 9782460
TI  - Regulation of the cholinergic gene locus.
AB  - DNase I hypersensitive site mapping of the human cholinergic gene locus has been
      used to detect cholinergic specific potential regulatory sites. Analysis of
      mutant PC12 cell lines provides evidence that protein kinase A II is required and
      coordinately regulates basal expression of both the ChAT and VAChT genes.

PMID- 9782461
TI  - [A case report. Ocular ischemia syndrome].

PMID- 9782462
TI  - [Eyeball growth after successful glaucoma surgery in the 1st year of life--follow
      up values for primary congenital glaucoma].
AB  - BACKGROUND: Echographic biometry of the ocular axial length is a helpful
      criterion in diagnosis and follow-up of primary congenital glaucoma. However,
      quantitative assessment of ocular growth following successful primary glaucoma
      surgery in the first year of life is hardly to find in literature. PATIENTS AND
      METHODS: In 36 eyes from 21 patients (mean age 4.4 +/- 2.4 months) with primary
      congenital glaucoma Ascan biometry was performed under general anesthesia before
      and 7.2 +/- 4.2 months following successful primary glaucoma surgery and
      retrospectively summarized. RESULTS: Preoperative axial length was 21.7 +/- 2.5
      mm, postoperative axial length was 22.4 +/- 1.6 mm. Ocular growth was
      significantly stronger in eyes with a preoperative axial length < 20 mm (p =
      0.0012) and in children younger than 3 months at surgery (p = 0.0004).
      CONCLUSIONS: Preoperative axial length and age are basic factors for the
      interpretation of ocular growth following glaucoma surgery in primary congenital
      glaucoma. Temporary cessation of ocular growth is a frequent finding after
      successful pressure-reducing surgery in eyes with axial length > 22 mm and in
      children aged 3 months or older.

PMID- 9782463
TI  - [Cataract surgery in patients with retinitis pigmentosa].
AB  - BACKGROUND: Because of the retinal alterations visual acuity of patients with
      retinitis pigmentosa is more affected by loss of contrast than in normal persons.
      Therefore cataract in retinitis pigmentosa (mostly posterior subcapsular
      cataract) leads earlier to decreasing visual acuity than is expected from the
      lens opacity. In a retrospective study we have looked up all patients with
      retinitis pigmentosa and cataract which were operated between 1989 and 1997 at
      our department. PATIENT AND METHODS: Between 1989 and 1997 50 eyes of 36 patients
      (21 female, 15 male; mean age 51 +/- 11.4 years) with the diagnosis of retinitis
      pigmentosa and cataract underwent extracapsular cataract extraction and IOL
      implantation. In a retrospective study we studied all case histories of these
      patients. Mean follow up time was 1.2 +/- 1.2 years. RESULTS: Preoperative visual
      acuity was 0.1 +/- 0.1, best postoperative visual acuity was 0.3 +/- 0.2. Visual
      field was not affected by cataract-surgery. Postoperative complications were not
      found. 2/3 of all patients were satisfied with the postoperative visual acuity,
      1/3 of all patients did not give comments. CONCLUSION: In patients with retinitis
      pigmentosa cataract surgery leads to significant increase of visual acuity.
      Cataract extraction should not be with held from patients with retinal dystrophy.

PMID- 9782464
TI  - [Radiotherapy only in severe, progressive endocrine orbitopathy: long-term
      results and comparison of various classification systems].
AB  - BACKGROUND: Therapeutic results after radiotherapy in thyroid associated
      orbitopathy (TAO) often are not comparable, because either different therapeutic
      methods at the same time or different scores were used in the evaluation. This
      study focuses on radiotherapy alone by means of different evaluation scores.
      PATIENTS AND METHODS: 60 patients (49 women, 11 men) received standard external
      beam radiotherapy (20 Gy: 10 fractions of each 2 Gy) as ultima ratio after
      failing different other therapies of thyroid associated orbitopathy. The mean
      interval from beginning of the symptoms to the radiotherapy was 17 +/- 36 months
      (between 6 and 240 months). The follow up was documented--classified by means of
      4 different scores--before radiotherapy, 6-12 weeks, 1 year after radiotherapy
      and at last follow up. The changes of symptom categories or grades of the
      different scores were analysed. RESULTS: Significant changes of the ophthalmic
      scores were observed when comparing the endpoints at 6-12 weeks, and at 1-year
      follow up after radiotherapy. The "classical" Werner score at 12 months follow up
      did not correlate well with the other TAO scores: American thyroid association
      (ATA) scoring system, Stanford scoring system, International ophthalmopathy
      index, while all other TAO scores revealed a high correlation among each other.
      According to the Orbitopathy Index (OI) of Grussendorf an improvement from 14.2
      points to 6.0 points was achieved. Soft tissue involvement and corneal
      involvement demonstrated the highest response rate (83/87%), extraocular muscle
      involvement and proptosis a good response rate (69/70%). No long-term
      complications were observed. CONCLUSION: According to this study there are
      indications that external beam radiotherapy is a suitable therapy even after
      pretreatment and a longer course of TAO. The OI, the ATA and the Stanford scoring
      systems lead to similar results in the assessment of thyroid orbitopathy.

PMID- 9782465
TI  - [Fundus autofluorescence in patients with hereditary macular dystrophies,
      malattia leventinese, familial dominant and aged-related drusen].
AB  - PURPOSE: The lack of histopathological material has placed limitation on our
      knowledge on the composition of focal deposits in eyes with macular dystrophies,
      malattia leventinese, dominant drusen and age related macular degeneration. This
      study was designed to study the composition of focal deposits in these eyes by
      documenting fundus autofluorescence in vivo. METHODS: Fundus autofluorescence was
      documented in 343 eyes of 199 subjects with macular dystrophies, malattia
      leventinese, dominant drusen and age-related macular degeneration using a laser
      scanning ophthalmoscope (Zeiss, Oberkochen; excitation wavelength: 488 nm,
      barrier filter at 521 nm). RESULTS: Autofluorescence of focal deposits was
      increased in eyes with macular dystrophies. In eyes with malattia leventinese and
      dominant drusen autofluorescence intensity of focal deposits showed a wide
      spectrum. In contrast, autofluorescence of age-related drusen was within normal
      limits. Background autofluorescence intensity was increased in eyes with macular
      dystrophies and within normal limits in eyes with malattia leventinese, dominant
      drusen and age-related drusen. CONCLUSION: The technique of in-vivo recording of
      fundus autofluorescence allows the differential diagnosis between macular
      dystrophies/malattia leventinese, dominant drusen/age related drusen when
      otherwise not possible.

PMID- 9782466
TI  - [Wolfgang Stock, his ophthalmopathologic collection and progress in glaucoma
      treatment in the 2nd half of the 20th century].
AB  - BACKGROUND: As long as Wolfgang Stock was head of the University Eye Clinic
      Tubingen (1921-1952), he founded a voluminous collection of ophthalmopathological
      slides, which reflect the knowledge about and possible therapies for various eye
      diseases at that time. MATERIAL: The "Collection Stock" contains ca. 450 glaucoma
      specimens. Of these, 50 were chosen at random and investigated macroscopically
      and microscopically. Each specimen was supplied with a (main) diagnosis. For
      comparison, 50 eyes with glaucoma enucleated between 1992 and 1997 were examined.
      RESULTS: Nowadays, "glaucoma enucleation" is performed nearly exclusively because
      of secondary angle closure glaucoma. In contrast, the "Collection Stock" contains
      various eyes with 1. primary glaucoma without previous operation, 2. congenital
      glaucoma, 3. lens induced glaucoma, 4. aphakic glaucoma, and 5. complications
      after glaucoma surgery. No case of diabetic neovascular glaucoma or PEX-glaucoma
      was found. CONCLUSIONS: Due to improvement in ophthalmological care, development
      of various pressure-lowering and anti-inflammatory drugs, new surgical techniques
      and, probably most important, introduction of the operation microscope, major
      advances concerning glaucoma therapy and avoidance of complications have been
      achieved in the last 50 years. Thus, the spectrum of "glaucoma enucleations" has
      changed dramatically, and certain types of (open angle) glaucoma Wolfgang Stock
      was very familiar with have in modern ophthalmopathological practice almost
      fallen into oblivion.

PMID- 9782467
TI  - [Correlation between glucose and lactate concentrations in the human cornea and
      in organ culture medium].
AB  - BACKGROUND: Metabolic changes of the human donor cornea during organ-culture are
      not at all reflected by the endothelium. Therefore metabolic investigations have
      become of increasing interest. It was the aim of this study to determine the
      correlation between glucose and lactate in storage medium and within the cornea
      itself and to find thereby an additional parameter for glucose metabolism during
      organ-culture. METHODS: Glucose and lactate were examined in 166 organ-culture
      medium samples as well as in 106 human corneas by enzymatical optical methods.
      Investigations were carried out after 1, 7, 15, 21 and 28 days of organ-culture.
      RESULTS: Glucose consumption was highest during the first two weeks of organ
      culture. Glucose concentrations showed a good linear correlation between medium
      samples and the cornea (r = 0.923). The correlation coefficient for lactate was
      worse (r = 0.733). CONCLUSION: Glucose and lactate levels in the organ-culture
      medium can be used as a marker for glucose metabolism in the cornea.

PMID- 9782468
TI  - [Atypical constellation of findings in Schimmelpenning-Feuerstein-Mims syndrome-
      case report and overview].
AB  - BACKGROUND: The Schimmelpenning-Feuerstein-Mims-syndrome is a phacomatosis of
      unknown pathogenesis and is presumed to be based on alterations in early
      embryogenesis. The syndrome is expressed by congenital nevi characterized by
      hyperplasia of the sebaceous glands and papillary acanthosis. Other
      manifestations include ophthalmic, neurologic, cardiovascular, skeletal and
      urogenital involvement. Eye-findings are variable and may affect all parts of the
      organ. All patients have a nevus sebaceus of the skin and many of them are
      described to suffer from seizures and/or mental retardation and/or abnormalities
      of the central nervous system/skull. The atypical constellation of findings in
      our case makes it of interest to report and give a short review. PATIENT: A 17
      year-old boy with Schimmelpenning-Feuer-stein-Mims-syndrome has been followed up
      by us since birth. RESULTS: Beside an unilateral combined nevus sebaceus and
      verrucosus of the face, neck and skull and an aplasia of a rib there were marked
      ocular symptoms. The affected right eye showed a dermoid, a wide lid-opening,
      microcornea, stenosis of the lacrimal ducts, a high myopic fundus, the optic disc
      with an inverse conus and a posterior scleral staphyloma. There were no seizures
      or mental retardation combined with normal radiologic findings of the central
      nervous system and the skull. CONCLUSION: The presented findings in our patient
      with Schimmelpenning-Feuerstein-Mims-syndrome emphasized the high variability of
      the expression of this disease, which may lead to difficulties in establishing
      correct diagnosis to prevent unnecessary examinations and inadequate therapies.

PMID- 9782469
TI  - [A familial anterior corneal degeneration: clinical aspects, histopathology and
      differential diagnosis].
AB  - BACKGROUND: We report on three cases of a progressive anterior corneal
      degeneration with clinical characteristics of limbal insufficiency occurring in
      three persons in three consecutive generations of one family. The disease has not
      yet been described in literature. PATIENTS: A woman aged 68, her 51 years old son
      and his 19 years old son are affected by the disease, which suggests autosomal
      dominant inheritance. None of the affected family members suffers from any form
      of collagenosis, endocrine insufficiency, chronic dermatosis, alteration of fat
      metabolism or other relevant systemic diseases. There is no accompanying disease
      of lids and conjunctiva except of a keratoconjunctivitis sicca with alteration of
      the mucin phase. The youngest affected member has a binocular anterior polar
      cataract. In the eldest affected member we performed penetrating keratoplasty.
      HISTOPATHOLOGY: Revealed thinning of corneal epithelium, moderate intra- and
      subepithelial granulocytary infiltration, a marked hyaline thickening of Bowman's
      membrane. The adjacent stroma showed accumulation of granulocytes and an
      increased number of capillaries and fibroblasts. Posterior stroma, Descemet's
      membrane and endothelium were normal. There were no goblet cells in the central
      epithelium. CONCLUSIONS: The appearance of the disease in three consecutive
      generations (strongly suggesting autosomal dominant inheritance) and the
      progressivity are characteristics of a dystrophical process. Development of a
      circular pannus and infiltration of epithelium and stroma with granulocytes
      however classify the disease as a degeneration, clinically and pathologically
      similar to Salzmann's nodular degeneration and to autosomal dominantly inherited
      keratitis.

PMID- 9782470
TI  - [Acute reversible night blindness caused by vitamin A deficiency in pancreatic
      carcinoma].
AB  - BACKGROUND: Vitamin A deficiency is a leading cause of blindness in childhood in
      the developing countries. In developed countries xerophthalmia occurs mainly as
      secondary hypovitaminosis due to malabsorption in chronic alcoholism or
      intestinal disorders. PATIENT AND METHODS: A 24-year-old female patient
      complained of night blindness since one week. There was a history of pancreas
      tail resection combined with radiation due to a papillary low grade cystic
      carcinoma at the age of 15. During a review period of 9 years of follow-up there
      was a slow disseminated metastatic spread including the liver. Despite a
      progressive tumor cachexia the patient was practising a profession. Visual acuity
      was 20/20 OU with normal visual fields. Dark adaptation was reduced to one log
      unit and scotopic electroretinography was extinguished. Serum vitamin A level was
      reduced to 75 ng/ml (normal range 400-700 ng/ml). RESULTS: Under vitamin A
      substitution dark adaption and scotopic electroretinography normalized and night
      blindness disappeared within 7 days. CONCLUSIONS: In malabsorption syndromes,
      especially in combination with liver manifestations, xerophthalmia should be
      considered as a potential complication. Vitamin A substitution should be
      administered if necessary. In cases of malignant tumors differential diagnosis
      includes the cancer associated retinopathy (CAR).

PMID- 9782471
TI  - [Recurrent pterygium over 15 years: epibulbar cartilaginous findings].
AB  - BACKGROUND: Epibulbar and extraocular cartilage bearing tumors in adults are
      extremely rare. PATIENT: A nasally located pterygium in a 24-year-old patient was
      excised and recurred over the ensuing 15 years six times requiring local
      excisions, and each time a histological diagnosis of pterygium was made. Only a
      curative excision including a biopsy of the insertion of the m. rectus medialis
      and a sclerokeratoplasty revealed the tumor to bear cartilage histologically in
      an unusual place. A Ruthenium-106 brachytherapy was followed by a triple
      procedure for visual rehabilitation, and no further recurrences were observed.
      CONCLUSION: The differential diagnosis of a cartilaginous tumor most likely a
      choristoma growing in an unusual localisation should be considered in adults
      suffering from recurrent pterygia without known physical risk factors, and a
      curative excision be performed. Further treatment options depend on the
      appearance of the tumor.

PMID- 9782473
TI  - [Acute preretinal hemorrhage before life threatening complications of
      subarachnoid hemorrhage].
AB  - BACKGROUND: To report on a patient with acute preretinal and intraretinal
      bleedings as first clinical signs of a life-threatening subarachnoid hemorrhage.
      PATIENT: A 36-year-old, so far healthy woman complained of decreased vision,
      which had started eight hours before. She presented herself in good general
      condition. Ophthalmoscopic evaluation showed intraretinal hemorrhages in both
      eyes and a preretinal hemorrhage in the left eye. During the examination, the
      patient fainted and suffered generalized seizure. Cranial computed tomography
      revealed a subarachnoid hemorrhage originating from an internal carotid artery
      aneurysm. CONCLUSION: Acute intraretinal and preretinal bleedings in apparently
      healthy patients can be precursors of eventually life-threatening complications
      of subarachnoid hemorrhages.

PMID- 9782472
TI  - [Conjunctival cysts of the orbits: clinical aspects and histology in 4 patients].
AB  - BACKGROUND: Only a few reports concerning congenital conjunctival cysts of the
      orbit (primary nonkeratinized epithelial cysts) have been published. PATIENTS: We
      describe four further cases of conjunctival cysts of the orbit, which were
      observed between 1995 and 1997 in Tubingen and Vienna. Histologically, all cysts
      were lined by nonkeratinizing epithelium with goblet cells. Epidermal appendages
      were found in the wall of one cyst. The patients' age was between 1 and 32 years.
      Clinically, the prominent symptom was swelling of the upper eyelid, persisting in
      three patients for more than several years. In one patients diplopia and
      restriction of eye movements developed within several weeks. CONCLUSIONS: The
      cases we described are in accordance with the cases reported in the literature.
      Often a swelling of the upper eyelid persisted for several years, before the cyst
      has become symptomatic predominantly in an adult patient. In contrast to dermoid
      or epidermoid cysts, there is no bony erosion and the cysts are located in the
      superior to nasal orbit. These cysts are probably more common as it is
      represented in the literature.

PMID- 9782474
TI  - [Observations on the pH value of various artificial tears preparations].
AB  - BACKGROUND: The pH-values of artificial tears have not been examined up to now.
      MATERIALS AND METHODS: The pH-values of 20 commercially available artificial
      tears were determined. RESULTS: pH-values measured from 4.82 to 8.39. One sixth
      showed pH-values above physiological values. CONCLUSION: A remarkable proportion
      of commercially available artificial tears deviate from the physiological range
      of the pH. It does not seem advisable to apply those in eyes with damaged
      anterior segments.

PMID- 9782475
TI  - [Chronic interstitial lung diseases in childhood: bronchopulmonary dysplasia and
      exogenous allergic alveolitis].
AB  - Bronchopulmonary dysplasia (BPD) is a chronic lung disease that develops in
      preterm infants treated with oxygen and positive-pressure ventilation for
      respiratory distress syndrome. Despite the introduction of new treatment
      modalities (surfactant therapy, high-frequency oscillation) and improvements in
      the outcome of critically ill preterm infants, BPD has become an extremely
      important complication of neonatal intensive care and the most common form of
      chronic lung disease in infants. Specific pathogenesis, treatment modalities,
      prognosis, and multidisciplinary approaches to the prevention of BPD are
      described in detail. Extrinsic allergic alveolitis ("hypersensitivity
      pneumonitis") is a rare pulmonary disease in childhood due to inhaled organic
      dust, containing fungal antigens, thermophilic actinomycetes, or avian proteins.
      Diagnosis is often difficult, but it should be considered in every child with
      persistent and otherwise unexplained respiratory symptoms.

PMID- 9782476
TI  - [Interstitial lung diseases with pulmonary hypertension associated with
      epidermolysis bullosa in an infant].
AB  - Interstitial lung diseases, with or without pulmonary hypertension and
      epidermolysis bullosa are rare in infancy. Pathogenetic correlations between
      these disease are not known and their coincidence has not been reported, yet. We
      report on a seven weeks old boy of consanguine parents with typical skin
      efflorescences of epidermolysis bullosa, tachydyspnoea and cyanosis.
      Echocardiography and cardiac catheterisation revealed pulmonary hypertension,
      which persisted under therapy with oxygen and nifedipin. Lung biopsy showed
      interstitial and peribronchiolar increased lymphocytes and lymphfollicels, a mild
      intraalveolar desquamation and a media hypertrophy of the arteries. A combined
      therapy of prednisone and nifedipine normalised the pulmonary hypertension and
      the oxygen saturation. The activity of the epidermolysis bullosa showed no
      correlation with the interstitial lung disease or with the therapy. A connection
      between both diseases is discussed.

PMID- 9782477
TI  - [Mastoiditis in childhood].
AB  - BACKGROUND: Despite new antibiotics mastoiditis in children still is a serious
      infection confronting the pediatrician and otolaryngologist with diagnostic and
      therapeutic problems. PATIENTS AND METHODS: In a retrospective study we reviewed
      the charts of 48 children who had a mastoidectomy from 1990 to 1995 in the
      Department of Oto-Rhino-Laryngology at the University of Essen. RESULTS: 60% of
      the patients presented with a retroauricular swelling, and a pathologic tympanic
      membrane was found in 89%. The erythrocyte sedimentation rate as the most
      valuable laboratory parameter was increased in 95% of cases. Larger
      osteodestructive lesions as a complication of mastoiditis could be predicted in
      three of ten cases by plain x-ray of the temporal bone. The most common bacteria
      to be isolated were Staphylococcus aureus, Streptococcus pneumoniae and
      Pseudomonas aeruginosa. CONCLUSION: Because of potential endocranial
      complications (10% in our patients) as well as difficult radiologic diagnosis of
      osteodestructive lesions by plain x-ray, we advocate mastoidectomy instead of a
      mere pharmacological therapy in the treatment of mastoiditis.

PMID- 9782478
TI  - [Quality assurance in therapy of mucoviscidosis: value of the Bonn patient
      information system].
AB  - BACKGROUND: Differences in the survival rates of patients in two large CF-clinics
      (Toronto, Boston) were explained by differences in dietary regimens: Toronto
      favoured a fat-enriched diet and had the better outcome. This example may explain
      how important high quality medical data are for improving treatment and prognosis
      of CF. AIM: A local patient-information-system is described to improve internal
      and external quality control. RESULTS: The system was developed over years in a
      fruitful collaboration between a realistic statistician and active CF doctors. It
      is easy to use and facilitates documentation, follow-up, researches and
      preparation of data for scientific presentation and clinical routine. Graphical
      outline may be used to motivate individual patients. Internal controlling for
      plausibility improves quality of data also serving the national system for
      quality control. CONCLUSIONS: We believe, our system is able to improve internal
      quality control and to serve the national system for quality control very
      efficiently without additional workload of the local CF-clinic.

PMID- 9782479
TI  - [Effect of dexamethasone and spironolactone therapy in calcium and phosphate
      homeostasis in premature infants with a birth weight under 1,500 g].
AB  - BACKGROUND: Dexamethasone and spironolactone are widely used in the management of
      bronchopulmonary dysplasia in premature infants. There are few data available
      about adverse effects of this drugs on the urinary excretion of calcium and
      phosphate in this group of patients. PATIENTS: 24 h-urine samples could be
      collected in 85 infants between 8 and 40 days. 31 infants received dexamethasone
      and 32 spironolactone. METHODS: Multivariate variance analysis was performed to
      study the influence of dexamethasone and spironolactone on the measured excretion
      of calcium and phosphate. The influence of gestational and postnatal age, calcium
      and phosphate intake and theophylline treatment were excluded by use as
      covariates. RESULTS: Spironolactone showed no significant influence on the
      urinary excretion of calcium or phosphate. Dexamethasone treatment increased the
      daily excretion of phosphate in the urine and decreased the phosphate
      concentration in serum. CONCLUSION: None of the examined drugs showed a
      significant increase of the renal excretion of calcium in preterm infants. Thus a
      higher risk of nephrocalcinosis development due to these drugs has not been
      confirmed. Dexamethasone treatment might increase the risk of osteopenia by
      enhancing phosphate excretion.

PMID- 9782480
TI  - [Atenolol for preventing recurrence of atrioventricular reentry tachycardia in
      childhood].
AB  - BACKGROUND: Supraventricular reentrant tachycardias are the most common cardiac
      arrhythmia observed in infancy and childhood. The often benign clinical course of
      the disease warrants careful selection of any antiarrhythmic drug given to
      prevent recurrencies, in order to avoid potentially dangerous side-effects such
      as proarrhythmia. This study reports our experience with atenolol in the longterm
      treatment of infants and children with supraventricular tachycardias. PATIENTS
      AND METHODS: A search of our database was made and all the children admitted in
      our institution between 1987 and 1995 for treatment of supraventricular
      tachycardia were selected. Patients who had longterm oral treatment with atenolol
      were retrospectively evaluated and were seen during 1996 in our outpatient clinic
      for a follow-up examination including a Holter-monitor. RESULTS: 14 infants and
      children with a median age of 2 9/12 years at first presentation could be
      evaluated. In 10 patients, atenolol was the first antiarrhythmic drug given. In
      10 of the patients (72%) therapy with atenolol was considered successful and no
      further attacks of tachycardia occurred. In 2 patients a partial response to
      atenolol was seen with an important decrease in the frequency of tachycardias.
      Two patients showed no effect of treatment and the betablocker was withdrawn. The
      effect of the drug on heart rate and blood pressure was mild and did not lead to
      symptoms. In no case had the drug to be withdrawn for adverse effects. After a
      mean follow-up of 50 months (3-105 months), 7 patients were off the drug and free
      of recurrencies while among the 5 children still on atenolol, only one
      experienced rare episodes of tachycardia. CONCLUSION: Atenolol is efficient in
      the longterm treatment of supraventricular tachycardias and due to its favorable
      risk profile can be recommended as first line treatment option.

PMID- 9782481
TI  - Alpha-interferon treatment in HBeAg positive children with chronic hepatitis B
      and associated hepatitis D.
AB  - The main problem of children with HBeAg positive hepatitis B and associated
      hepatitis D is progression to liver cirrhosis with decompensation of liver
      function and need for liver replacement therapy within 15-20 years after
      infection. To determine whether interferon-alpha (IFN-alpha) therapy has a
      positive effect on HBV replication and inflammatory activity, we evaluated
      clinical and serological data of 8 children treated with IFN-alpha and 6 historic
      control patients without treatment. 4 of the nontreated patients seroconverted
      from HBeAg to anti-HBe between 7 to 17 years after initial diagnosis and showed
      decreased inflammatory activity in the liver. In the treatment group, the rate of
      seroconversion to anti-HBe (3 early, 2 late seroconverters) corresponded well to
      former trial results obtained in patients exclusively infected by HBV. Serum
      aminotransferase levels decreased or normalized in seroconverted children. In
      chronic HBV infection with associated hepatitis D (HDV) infection--compared to
      the spontaneous course of the disease--IFN-alpha therapy reduced inflammatory
      activity by earlier seroconversion to anti-HBe in responding patients. Moreover,
      viral replication and infectivity of hepatitis B was markedly reduced, but no
      effect on replication of HDV could be documented. Although long-term effects
      cannot be exactly estimated, at present IFN-alpha remains the only available
      treatment for HBeAg and anti-HDV positive children and seems to be of benefit for
      responding patients.

PMID- 9782482
TI  - [Incidence of increased serum Helicobacter pylori IgG antibodies in children with
      and without chronic abdominal pain].
AB  - The prevalence of Helicobacter pylori (HP) IgG antibodies was analysed in a group
      of 142 asymptomatic children (group A) and in 31 pediatric patients (group B)
      with recurrent abdominal pain. HP IgG antibodies were measured by a commercially
      available fluorescence-enzyme immuno-assay test (Heloritest IgG, Fa Eurospital).
      In asymptomatic children the prevalence of HP IgG antibodies increased
      significantly with age from 17% with 6 years to more then 40% with 14 years. A
      higher prevalence of HP IgG antibodies was found in children living in more
      crowded housing conditions. Comparing the number of HP IgG positive children in
      group B (58%) to a matched population from group A (35%) no statistically
      different prevalence rates were found. Thus HP IgG antibodies are found in
      similar frequencies, in both, symptomatic and asymptomatic children. Therefore
      the presence of HP-IgG antibodies does not necessarily indicate that the HP
      infection is the cause for the recurrent abdominal pain in these children.

PMID- 9782483
TI  - [Intratesticular epithelial cyst in an infant].
AB  - We report on a 7-month-old boy with a simple cyst of the testis who was treated
      with excision and testicular preservation. Benign testicular tumors are more
      common in children than in adults (30%). Ultrasound may permit identification of
      benign testicular lesions. As simple cysts are isolated benign entities they may
      be treated by testisparing surgery.

PMID- 9782484
TI  - [Differentiated thyroid gland carcinoma in children and adolescents].
AB  - Differentiated thyroid cancer is a rare disease in childhood and adolescence.
      Most frequently, thyroid cancer in children belongs to the papillary variant,
      whereas a follicular histological pattern is much less frequently encountered.
      Dedifferentiated (anaplastic) cancers are very rare at this age. Especially
      indolent cervical lymph node enlargement is suspicious for a thyroid cancer, even
      more when occurring together with a solitary, rapidly growing, and indurated
      thyroid nodule. Every nodule in the thyroid of children and adolescents, if not
      unequivocally cystic, is suspicious of a malignancy. In contrast to adults,
      multifocal tumor manifestations are frequently found in children and adolescents
      which often have spread beyond the capsule of the thyroid at the time of
      diagnosis. Regional lymph nodes are involved in up to 90%, and distant metastases
      are present in up to 20% of the cases. Despite these much more advanced stages as
      usually found in adults, the prognosis of children is better than at advanced
      age, since these tumors are highly differentiated, and, even in the case of
      distant metastases, a curative approach is still possible. The therapy
      (surgery/radioiodine) and the follow-up follows the same principles as those
      which have been established for older patients.

PMID- 9782485
TI  - Agricultural and medical microbiology: a time for bridging gaps.

PMID- 9782486
TI  - The mvrA locus of Escherichia coli does not encode a ferredoxin-NADP+ reductase.

PMID- 9782487
TI  - Biochemistry of methanogenesis: a tribute to Marjory Stephenson. 1998 Marjory
      Stephenson Prize Lecture.

PMID- 9782489
TI  - Cloning and sequencing of the Candida albicans homologue of SRB1/PSA1/VIG9, the
      essential gene encoding GDP-mannose pyrophosphorylase in Saccharomyces
      cerevisiae.
AB  - Two genomic fragments have been isolated from Candida albicans which strongly
      hybridize to SRB1/PSA1/VIG9, an essential gene which encodes GDP-mannose
      pyrophosphorylase in Saccharomyces cerevisiae. A common 2.5 kb Xbal-Pstl fragment
      has been identified, which Southern analysis suggests is most likely unique in
      the C. albicans genome. The fragment contains an ORF, which is 82% identical and
      90% homologous to the Srb1p/Psa1p/Vig9p from S. cerevisiae, contains one
      additional amino acid at position 254 and is able to functionally complement the
      major phenotypic characteristics of S. cerevisiae srb1 null and conditional
      mutations. The authors therefore conclude that they have cloned and sequenced
      from C. albicans the bona fide homologue of SRB1/PSA1/VIG9, named hereafter
      CaSRB1. Northern analysis data indicate that the gene is expressed in C. albicans
      under conditions of growth in the yeast and hyphal form and suggest that its
      expression might be regulated.

PMID- 9782488
TI  - A controllable gene-expression system for the pathogenic fungus Candida glabrata.
AB  - A system for controlling gene expression was established in the pathogenic fungus
      Candida glabrata to elucidate the physiological functions of genes. To control
      the expression of the gene of interest, the C. glabrata cells were first
      transformed with the plasmid carrying the tetracycline repressor-transactivator
      fusion tetR::GAL4, then with the DNA fragment containing the controllable
      cassette, the tetracycline operator chimeric promoter (tetO::ScHOP1). The peptide
      elongation factor 3 (CgTEF3) and DNA topoisomerase II (CgTOP2) genes from C.
      glabrata were cloned and their expression assessed using this system. When the
      promoter of CgTEF3 or CgTOP2 was replaced with tetO::ScHOP1, doxycycline almost
      completely repressed the expression of both mRNAs, and impaired growth.
      Repression of the TOP2 or TEF3 gene by doxycycline also hampered the survival of
      C. glabrata cells in mice; in mouse kidneys the number of C. glabrata cells, in
      which the TOP2 or TEF3 promoter was replaced with the tetO::ScHOP1 controllable
      cassette, did not increase when the mice were given doxycycline. Thus, it appears
      that the gene repression mediated by doxycycline occurred not only in culture
      media but also in animals; therefore, this system can be used to elucidate the
      function of the gene in fungal infections and pathogenesis.

PMID- 9782490
TI  - Bacteria in post-glacial freshwater sediments.
AB  - Prokaryote communities in post-glacial profundal freshwater sediments of
      Windermere, representing 10-12,000 years of deposition, were examined for
      culturability, viability and community structure. The potential for active
      geochemical cycles was inferred from the presence of specific groups of bacteria.
      Direct count procedures revealed 10(12) cells (g dry wt sediment)-1 in the
      surface sediments, which declined to approximately 10(9) cells (g dry wt
      sediment)-1 at 6 m depth of core (Representing approximately 10,000 years of
      deposition). The majority of the cells in the upper sediments were metabolically
      active when challenged with viability probes and responded to the direct viable
      count method. Below 250 cm, viability shown by 5-cyano-2,3-diotyl tetrazolium
      chloride (CTC) dye was not significantly different from the direct count;
      however, counts obtained with 5-carboxyfluorescein diacetate (CFDA) and the
      direct viable count both declined significantly from the direct count below 250
      cm and 1 m, respectively. Culture was achieved from samples throughout the core,
      although the numbers of culturable bacteria decreased significantly with depth,
      from 10(7) c.f.u. (g dry wt sediment)-1 to 10(1)-10(2) c.f.u. (g dry wt sediment)
      1 below 3 m depth. Among culturable isolates, Gram-positives and Gram-negatives
      were found at all levels of the core, and spore-forming heterotrophs dominated.
      Although sulphate-reducing bacteria were not detected below 20 cm, isolates
      demonstrating denitrifying activity were detected at all depths. PCR performed on
      samples taken below 3 m (deposited more than 7000 years ago) using eubacterial
      and archaeal primers revealed sequences similar to those found in deep sediments
      of the Pacific Ocean and the presence of methanogenic archaea. These observations
      indicate that bacteria and archaea are capable of long-term persistence and
      activity in deep, aged freshwater sediments.

PMID- 9782491
TI  - Genetic engineering of an industrial strain of Saccharopolyspora erythraea for
      stable expression of the Vitreoscilla haemoglobin gene (vhb).
AB  - Several Actinomycetes/Streptomycetes expression vectors are described for
      expression of the Vitreoscilla haemoglobin gene (vhb) in an industrial
      erythromycin-producing strain of Saccharopolyspora erythraea. Cloning of vhb
      under the control of either the thiostrepton-inducible PtipA promoter or the
      constitutive PermE* promoter led to the production of chemically active
      haemoglobin (VHb) in Streptomyces lividans TK24 transformed with these
      constructs. However, theplasmids could not be transformed into Sac. erythraea.
      Transformants of Sac. erythraea and/or exconjugants were obtained using a novel
      Escherichia coli/Streptomyces shuttle vector comprised of vhb under the control
      of the PermE* promoter, the Streptomyces plasmid pIJ350 origin of replication,
      the thiostrepton-resistance gene (tsr) for selection, and the oriT region which
      is necessary for conjugal transfer. Increased plasmid stability in Sac. erythraea
      was obtained by construction of a vector for chromosomal integration. This vector
      contained the Streptomyces phage phi C31 attachment site for chromosomal
      integration and vhb expressed under the PmerR promoter and was stably maintained
      in the chromosome of Sac. erythraea. Shake-flask cultivations of the transformed
      Sac. erythraea strain with the chromosomally integrated vhb gene show that vhb is
      expressed in an active form. The corresponding amount of erythromycin produced in
      the vhb-expressing strain was approximately 60% higher relative to the original
      VHb-negative strain.

PMID- 9782492
TI  - Nitrogen-starvation-induced chlorosis in Synechococcus PCC 7942: adaptation to
      long-term survival.
AB  - When deprived of essential nutrients, the non-diazotrophic cyanobacterium
      Synechococcus sp. strain PCC 7942 undergoes a proteolytic degradation of the
      phycobiliproteins, its major light-harvesting pigments. This process is known as
      chlorosis. This paper presents evidence that the degradation of phycobiliproteins
      is part of an acclimation process in which growing cells differentiate into non
      pigmented cells able to endure long periods of starvation. The time course of
      degradation processes differs for various photosynthetic pigments, for
      photosystem I and photosystem II activities and is strongly influenced by the
      illumination and by the experimental conditions of nutrient deprivation. Under
      standard experimental conditions of combined nitrogen deprivation, three phases
      of the differentiation process can be defined. The first phase corresponds to the
      well-known phycobiliprotein degradation, in phase 2 the cells lose chlorophyll a
      prior to entering phase 3, the fully differentiated state, in which the cells are
      still able to regenerate pigmentation after the addition of nitrate to the
      culture. An analysis of the protein synthesis patterns by two-dimensional gel
      electrophoresis during nitrogen starvation indicates extensive differential gene
      expression, suggesting the operation of tight regulatory mechanisms.

PMID- 9782493
TI  - Fluorescence in situ hybridization shows spatial distribution of as yet
      uncultured treponemes in biopsies from digital dermatitis lesions.
AB  - Fluorescence in situ hybridization (FISH) was performed on sections of plastic
      embedded tissue using 16S rRNA-directed oligonucleotide probes to visualize
      uncultured treponemes in skin biopsies of cows with digital dermatitis. Plastic
      as embedding material allowed sectioning of hard and soft tissue with a defined
      thickness, avoiding the risk of dragging bacteria into the tissue while
      sectioning. furthermore, it provided a good signal-to-noise ratio. Using this
      method the spatial distribution of three different bacterial phylotypes was
      visualized simultaneously within the tissue. Whereas debris covering the ulcers
      contained a mixture of different micro-organisms, a layering of certain
      treponemal phylotypes was observed deeper in the epidermis. Confocal laser
      scanning microscopy and subsequent three-dimensional reconstruction of series of
      optical sections confirmed that the treponemes migrated intercellularly around
      the cells, most of them directed towards the dermis. In situ hybridization on
      tissue embedded in plastic proved to be a useful method to study mixed bacterial
      infections since it combines excellent histological conservation of tissue with
      identification of bacterial species by simultaneous use of probes labelled with
      different fluorescent dyes. This technique may have implications for in situ
      detection, identification and localization of microorganisms in veterinary as
      well as in human medicine.

PMID- 9782494
TI  - The role of environmental factors in the regulation of virulence-determinant
      expression in Staphylococcus aureus 8325-4.
AB  - Staphylococcus aureus is a major human pathogen, which produces a variety of
      virulence determinants. To study environmental regulation of virulence
      determinant production, several transcriptional reporter gene fusions were
      constructed. Chromosomal fusions were made with the staphylococcal accessory
      regulator (sarA), alpha-haemolysin (hla), surface protein A (spa) and toxic-shock
      syndrome toxin-1 (tst) genes. The effect of many different environmental
      conditions on the expression of the fusions was examined. Expression of hla, tst
      and spa was strongly repressed in the presence of sodium chloride (1 M) or
      sucrose (20 mM), but sarA was relatively unaffected. The global regulator of
      expression of virulence-determinant genes, agr (accessory gene regulator) was not
      involved in the salt or sucrose repression. Novobiocin, a DNA gyrase inhibitor,
      did not significantly increase the expression of tst in wild-type or agr
      backgrounds and failed to relieve the salt suppression. Expression of tst was
      strongly stimulated in several low-metal environments, independently of agr,
      whilst spa levels were significantly reduced by EGTA. The complex, interactive
      role of environmental factors in the control of expression of the virulence
      determinants is discussed.

PMID- 9782495
TI  - Airway hyper-responsiveness to neurokinin A and bradykinin following Mycoplasma
      pneumoniae infection associated with reduced epithelial neutral endopeptidase.
AB  - To determine whether mycoplasma infection produces airway hyper-responsiveness to
      tachykinins and bradykinin and, if so, to elucidate the role of neutral
      endopeptidase (NEP), isolated hamster tracheal segments were studied under
      isometric conditions in vitro. Nasal inoculation with Mycoplasma pneumoniae
      potentiated contractile responses to neurokinin A and bradykinin, causing a
      leftward shift of the dose-response curves to a lower concentration by 1 log unit
      for each agonist, whereas there was no response with acetylcholine. Pretreatment
      of tissues with the NEP inhibitor phosphoramidon augmented neurokinin A- and
      bradykinin-induced contractions in saline-treated control tissues, but did not
      further potentiate the responsiveness in M. pneumoniae-infected tissues. NEP
      activity in the tracheal epithelium, but not in epithelium-denuded tissues, was
      decreased in infected animals. These results suggest that M. pneumoniae infection
      causes airway bronchoconstrictor hyper-responsiveness to neurokinin A and
      bradykinin and that this effect may be associated with an inhibition of
      epithelial NEP activity.

PMID- 9782496
TI  - Altered expression and modification of proteases from an avirulent mutant of
      Porphyromonas gingivalis W50 (W50/BE1).
AB  - Proteases of Porphyromonas gingivalis are considered to be important factors in
      the virulence of this organism. A non-pigmenting mutant of P. gingivalis W50
      (W50/BE1) has been shown to be less virulent in animal models and to produce
      significantly less Arg-specific protease activity than the parent strain. Three
      proteases are present in the culture supernatant of P. gingivalis W50: RI, RIA
      and RIB. All three proteases are derived from prpR1, which encodes a polypeptide
      of 1706 amino acids that is organized into distinct domains (pro, alpha, beta and
      gamma). The aim of the present investigation was to purify and characterize the
      Arg-specific proteases produced by the avirulent W50/BE1 strain. Significant
      differences were observed between the proteases of P. gingivalis W50 and W50/BE1.
      The levels of RI present in the culture supernatant of W50/BE1 were lower than
      those present in W50, and RIA and RIB were absent. RI from W50/BE1 was composed
      of three polypeptide chains, unlike the enzyme from W50, which is a heterodimer.
      The remainder of the Arg-specific protease activity in W50/BE1 was derived from a
      second gene, prR2, and was present in two fractions, RIIAs/BE (soluble) and
      RIIAv/BE (vesicle-bound). This activity contained two peptide chains: a
      approximately 54 kDa chain corresponding to the protease domain and a
      approximately 26 kDa chain, derived from the propeptide domain of the PrRII
      precursor. No enzyme with large glycan additions, equivalent to RIB in the
      vesicle fraction of the wild-type W50, was present. These data indicate that the
      reduced level of extracellular protease activity in W50/BE1 reflects reduced
      synthesis and/or export of prpR1 enzymes, which is only partially compensated by
      synthesis of prR2-derived enzymes, and that all of these proteases undergo
      altered post-translational modification compared to the parent strain.

PMID- 9782497
TI  - Hydrolysis of the soft amphiphilic antimicrobial agent tetradecyl betainate is
      retarded after binding to and killing Salmonella typhimurium.
AB  - Hydrolysis of tetradecyl betainate (B14), a fast-acting microbicidal amphiphilic
      quaternary ammonium compound (QAC) being an ester of betaine and tetradecanol,
      occurred after binding to Salmonella typhimurium, resulting in release of the
      water-soluble betaine portion and retention of the lipophilic tetradecanol. The
      rate of the hydrolysis was significant but retarded in comparison to B14 in
      solution. As in free solution, the hydrolysis of substance bound to S.
      typhimurium was increased in an alkaline environment and by heat. At pH 6.0 and
      20 degrees C the hydrolysis of bound ester was about 10% after 180 min, whereas
      at pH 9.0 and 50 degrees C it was about 50% after 60 min. These results are
      consistent with a model where amphiphilic QACs are inserted into the bacterial
      outer membrane (OM) with the quaternary ammonium head group facing outwards and
      the lipophilic portion, including the ester bond, being in the membrane lipid
      environment enough for retarding the hydrolysis. However, calculation of the mean
      concentration of B14 in the bacteria at MBC99 (minimum bactericidal concentration
      required to kill 99% of cells) showed a 7000-8000 times greater concentration
      than in the medium. At this concentration, when most B14 is considered to be
      bound to the OM, the available surface area for each molecule was only 2 A2. This
      is only 6-7% of that required for close packing of the quaternary ammonium head
      group (30 A2), indicating that a three-dimensional, presumably continuous
      arrangement was formed. Since B14 is hydrolysed after its binding to bacteria
      with microbicidal effect, it may be used under conditions where stable QACs might
      be harmful to the close or the common environment.

PMID- 9782498
TI  - Structural, functional and mutational analysis of the pfr gene encoding a
      ferritin from Helicobacter pylori.
AB  - The function of the pfr gene encoding the ferritin from Helicobacter pylori was
      investigated using the Fur titration assay (FURTA) in Escherichia coli, and by
      characterization of a pfr-deficient mutant strain of H. pylori. Nucleotide
      sequence analysis revealed that the pfr region is conserved among strains (> 95%
      nucleotide identity). Two transcriptional start sites, at least one of them
      preceded by a sigma 70-dependent promoter, were identified. Provision of the H.
      pylori pfr gene on a multicopy plasmid resulted in reversal of the Fur-mediated
      repression of the fhuF gene in E. coli, thus enabling the use of the FURTA for
      cloning of the ferritin gene. Inactivation of the pfr gene, either by insertion
      of a resistance cassette or by deletion of the up- and downstream segments,
      abolished this function. Immunoblot analysis with a Pfr-specific antiserum
      detected the Pfr protein in H. pylori and in E. coli carrying the pfr gene on a
      plasmid. Pfr-deficient mutants of H. pylori were generated by marker-exchange
      mutagenesis. These were more susceptible than the parental strain to killing by
      various metal ions including irons, copper and manganese, whereas conditions of
      oxidative stress or iron deprivation were not discriminative. Analysis by element
      specific electron microscopy revealed that growth of H. pylori in the presence of
      iron induces the formation of two kinds of cytoplasmic aggregates: large vacuole
      like bodies and smaller granules containing iron in association with oxygen or
      phosphorus. Neither of these structures was detected in the pfr-deficient mutant
      strain. Furthermore, the ferritin accumulated under iron overload and the pfr
      deficient mutant strains lacked expression of a 12 kDa protein which was
      negatively regulated by iron in the parental strain. The results indicate that
      the nonhaem-iron ferritin is involved in the formation of iron-containing
      subcellular structures and contributes to metal resistance of H. pylori. Further
      evidence for an interaction of ferritin with iron-dependent regulation mechanisms
      is provided.

PMID- 9782499
TI  - Close proximity of the tdh, trh and ure genes on the chromosome of Vibrio
      parahaemolyticus.
AB  - The distribution and location of the virulence-factor genes of Vibrio
      parahaemolyticus, tdh and trh, and the structural gene of urease, ureC, were
      examined on the genomic DNAs of 115 clinical isolates of V. parahaemolyticus. The
      majority of strains (81%) had two copies of tdh on the chromosome, and no copies
      of trh or ure. Southern hybridization with a tdh probe, after pulsed-field gel
      electrophoresis of Notl-digested genomic DNA of each strain revealed only single
      bands, suggesting that the two copies of the exist on single Notl fragments in
      each strain. Of the 115 strains, 7% had the tdh, trh and ure genes on chromosomal
      DNA. The three genes were also detected on single Notl fragments in these
      strains. More detailed analysis revealed that the three genes were localized
      within 40 kb. By long and accurate polymerase chain reactions (LA-PCR) the
      distance between trh and ure was shown to be less than 8.5 kb. These results
      reveal a close proximity of the tdh, trh and ure genes on the chromosome of
      pathogenic V. parahaemolyticus strains.

PMID- 9782500
TI  - An in silico evaluation of Tn916 as a tool for generalized mutagenesis in
      Haemophilus influenzae Rd.
AB  - The transposon Tn916 was evaluated as a tool for generalized mutagenesis of the
      genome of Haemophilus influenzae. This was achieved in silico by searching the
      genome sequence of H. influenzae Rd for the published Tn916 target site consensus
      sequence 5' TT/ATTTT(N)6AAAAAA/TA. This search identified 16 putative target
      sites. In subsequent experiments, integration of Tn916 did not occur at any of
      these sites. Using the nucleotide sequences of these observed integration sites,
      a new consensus sequence, 5' TTTTT(N)xAAAAA (4 < or = x < or = 7), was derived.
      This sequence reflects the curve-twist-curve DNA topology which is a feature
      common to all Tn916 integration sites. A search of the H. influenzae Rd genome
      using the new consensus sequence identified 167 potential target sites,
      representing approximately 1% of the total genome. Only 80 of these sites were
      located within ORFs. The presence of such a limited number of target sites places
      severe constraints on the use of Tn916 as a tool for generalized mutagenesis of
      the genome of H. influenzae.

PMID- 9782501
TI  - Cloning of the haemocin locus of Haemophilus influenzae type b and assessment of
      the role of haemocin in virulence.
AB  - The bacteriocin haemocin (HMC) is produced by most type b strains of Haemophilus
      influenzae, including strains determined to be genetically diverse, and is toxic
      to virtually all non-type b strains of H. influenzae, both encapsulated and non
      encapsulated. Examination of the deduced amino acid sequences of several genes
      upstream of the previously identified HMC immunity gene (hmcI) revealed several
      features common to class II bacteriocins of certain Gram-positive bacteria.
      Mutagenesis of the open reading frame immediately upstream of hmcI resulted in a
      loss of the HMC production phenotype. When an HMC-producing strai of H.
      influenzae and the HMC-deficient isogenic mutant were compared for invasion on
      the infant-rat model, the HMC-producing strain was found to invade significantly
      earlier; however, a significantly higher number of rats infected with the
      isogenic mutant became bacteraemic as compared with those infected with the HMC
      producing parent.

PMID- 9782502
TI  - Mechanism of isoniazid uptake in Mycobacterium tuberculosis.
AB  - Initial transport kinetics of isoniazid (INH) and its uptake at the plateau were
      studied in Mycobacterium tuberculosis H37Rv under various experimental
      conditions. The initial uptake velocity increased linearly with INH concentration
      from 2 x 10(-6) M to 10(-2) M. It was modified neither by addition of a
      protonophore that abolished proline transport, nor following ATP depletion by
      arsenate, which inhibited glycerol uptake, two transport processes taken as
      controls for secondary active transport and facilitated diffusion, respectively.
      Microaerobiosis or low temperature (4 degrees C) were without effect on initial
      uptake. It is thus likely that INH transport in M. tuberculosis proceeds by a
      passive diffusion mechanism, and that catalase-peroxidase (KatG) is not involved
      in the actual transport. However, conditions inhibiting KatG activity (high INH
      concentration, microaerobiosis, low temperature) decrease cell radioactivity at
      the uptake plateau. It is proposed that INH transport occurs by passive
      diffusion. KatG is involved only in the intracellular accumulation of oxidized
      derivatives of INH, especially of isonicotinic acid, which is trapped inside
      cells in its ionized form. This model explains observed and previously known
      characteristics of the accumulation of radioactivity in the presence of [14C]INH
      for various species and strains of mycobacteria.

PMID- 9782503
TI  - Isolation of a unique benzothiophene-desulphurizing bacterium, Gordona sp. strain
      213E (NCIMB 40816), and characterization of the desulphurization pathway.
AB  - Gordona sp. strain 213E (NCIMB 40816) grew in pure culture in a mineral salts
      medium containing fructose as a source of carbon and energy, and benzothiophene
      (BTH) as the sole source of sulphur. During growth a phenolic compound
      accumulated, as indicated by the production of a blue colour on addition of
      Gibb's reagent. Therefore this pathway is analogous to the dibenzothiophene (DBT)
      desulphurization pathway of Rhodococcus sp. strain IGTS8, in which 2
      hydroxybiphenyl accumulates during growth with DBT as the sole sulphur source.
      Ethyl acetate extraction of the culture medium yielded the metabolites
      benzothiophene s-oxide (BTHO), benzothiophene s,s-dioxide (BTHO2),
      benzo[c][1,2]oxathiin 6-oxide (BcOTO), 2-(2'-hydroxyphenyl) ethan 1-al (HPEal)
      and benzofuran (BFU). The deduced pathway for BTH desulphurization is BTH-->BTHO-
      >BTHO2-->HPESi(-)-->HPEal. HPESi- is (Z)-2-(2'-hydroxyphenyl)ethen 1-sulphinate,
      the stable aqueous-solution form of BcOTO. It was concluded that HPEal was the
      Gibb's-reagent-reactive phenolic compound which accumulated in the culture medium
      of strain 213E during growth, and that the presence of BFU was due to partial
      condensation of HPEal during the ethyl acetate extraction procedure. Gordona sp.
      strain 213E was unable to grow in a mineral salts medium containing fructose as a
      source of carbon and energy and DBT as the sole sulphur source. BTH
      desulphurization-active cells (grown using BTH as sole sulphur source) were
      unable to desulphurize DBT. Likewise Rhodococcus sp. strain IGTS8 was unable to
      grow using BTH as the sole sulphur source, and DBT-desulphurization-active cells
      of strain IGTS8 (grown using DBT as sole sulphur source) were unable to
      desulphurize BTH. This absence of cross-reactivity is discussed in terms of
      fundamental differences in the chemistry of the DBT- and BTH-desulphurization
      reactions.

PMID- 9782505
TI  - Bacillus subtilis ORF yybQ encodes a manganese-dependent inorganic
      pyrophosphatase with distinctive properties: the first of a new class of soluble
      pyrophosphatase?
AB  - The N-terminal 15 amino acids of the major protein associated with inorganic
      pyrophosphatase activity in Bacillus subtilis WB600 are identical to those of B.
      subtilis ORF yybQ. This ORF was amplified from B. subtilis WB600 DNA by PCR and
      cloned into an overexpression vector in Escherichia coli. Induction of
      overexpression produced a soluble protein of 34,000 Da by SDS-PAGE and by matrix
      assisted laser desorption and ionization mass spectrometry. The overexpressed
      protein had a high specific activity for the hydrolysis of magnesium
      pyrophosphate, and was specifically and reversibly activated by Mn2+ ions. These
      properties are identical to those of inorganic pyrophosphatase purified from B.
      subtilis WB600. No significant similarity was found between the derived sequence
      of the B. subtilis yybQ-encoded protein and published sequences of identified
      inorganic pyrophosphatases of Eukarya, Bacteria or Archaea domains. However,
      there is significant similarity to three putative proteins of unknown function
      from the archaea Methanococcus jannaschii and Archaeoglobus fulgidus, and from
      Streptococcus gordonii. The genomes of B. subtilis, M. jannaschii and A. fulgidus
      do not contain sequences similar to those of hitherto known soluble inorganic
      pyrophosphatases. The present findings, together with a survey of the properties
      of inorganic pyrophosphatases from 38 different sources, suggest that the B.
      subtilis yybQ-encoded protein is the first fully characterized member of a new
      class of inorganic pyrophosphatase.

PMID- 9782504
TI  - Bacillus subtilis genes for the utilization of sulfur from aliphatic sulfonates.
AB  - A 5 kb region upstream of katA at 82 degrees on the Bacillus subtilis chromosome
      contains five ORFs organized in an operon-like structure. Based on sequence
      similarity, three of the ORFs are likely to encode an ABC transport system
      (ssuBAC) and another to encode a monooxygenase (ssuD). The deduced amino acid
      sequence of the last ORF (ygaN) shows no similarity to any known protein. B.
      subtilis can utilize a range of aliphatic sulfonates such as alkanesulfonates,
      taurine, isethionate and sulfoacetate as a source of sulfur, but not when ssuA
      and ssuC are disrupted by insertion of a neomycin-resistance gene. Utilization of
      aliphatic sulfonates was not affected in a strain lacking 3'-phosphoadenosine 5'
      phosphosulfate (PAPS) sulfotransferase, indicating that sulfate is not an
      intermediate in the assimilation of sulfonate-sulfur. Sulfate or cysteine
      prevented expression of beta-galactosidase from a transcriptional ssuD::lacZ
      fusion. It is proposed that ssuBACD encode a system for ATP-dependent transport
      of alkanesulfonates and an oxygenase required for their desulfonation.

PMID- 9782506
TI  - Construction of a single-copy integration vector and its use to study gene
      expression in Bacillus licheniformis.
AB  - A versatile system consisting of an integrational vector and a bacitracin (Bt)
      producing beta-galactosidase (beta-Gal)-negative (Lac-) Bacillus licheniformis
      TLH strain was constructed to quantify promoter activity and to study gene
      regulation in a single-copy set-up. The vector pTLH utilizes the promoterless
      Escherichia coli lacZ gene derived from pQF52 and contains the pBR322 origin of
      replication and a kanamycin-resistance gene for selection in both B.
      licheniformis and E. coli. The vector also contains an inner part of the first
      gene of the Bt synthetase (bts) operon which enables its integration into the bts
      of B. licheniformis by Campbell-type recombination. This recombination event can
      be easily tested on a Micrococcus flavus lawn where loss of Bt production, i.e.
      no clearing zone on the lawn, is indicative of the proper integration. The Lac-
      B. licheniformis TLH strain was developed by elimination of the natural beta-Gal
      activity of B. licheniformis strain ATCC 10716 UM12 using NTG mutagenesis.

PMID- 9782507
TI  - F- phenocopies: characterization of expression of the F transfer region in
      stationary phase.
AB  - The phenomenon of 'F- phenocopies' in which F+ cells become transfer-deficient in
      stationary phase seems contradictory to the proposed role for F transfer in
      adaptive mutation during stationary phase induced by nutrient limitation. The
      expression of a range of transfer genes at the transcriptional and translational
      level in stationary phase has been characterized as well as the degree of nicking
      at the origin of transfer, oriT. Transfer efficiency rapidly decreased in mid
      exponential phase, coincident with a decrease in traM transcripts. Approximately
      2 h later, the transcript for traA, encoding F-pilin, also decreased to
      undetectable levels. The levels of TraA (pilin), TraD, TraJ and TraT remained
      fairly constant well into stationary phase while the levels of TraM and Tral
      decreased to undetectable levels in early stationary phase. A null mutation in
      the gene for the alternative sigma factor, rpoS, did not affect mating efficiency
      or transcript levels but did increase the stability of TraM and Tral in
      stationary phase. Nicking at oriT was detected at maximal levels in early
      stationary phase and at low levels in late stationary phase. The results suggest
      that the F-pilus transfer apparatus is maintained in the cell envelope after
      transcription of the transfer region from the main promoter, Py, has ceased with
      down-regulation of traM transcription being the first step detected in this
      process. The presence of a low level of nicking at oriT in stationary phase is
      consistent with a role for F in promoting adaptive mutation.

PMID- 9782508
TI  - The vanadate-tolerant yeast Hansenula polymorpha undergoes cellular
      reorganization during growth in, and recovery from, the presence of vanadate.
AB  - When present at intracellular concentrations above micromolar, vanadate becomes
      toxic to most organisms. However, the yeast Hansenula polymorpha is able to grow
      on vanadate concentrations in the millimolar range, showing at the same time
      modifications in cellular ultrastructure and polyphosphate metabolism. Here, the
      development of the ultrastructural changes, and of vacuolar and secretory
      activities, during exponential growth on vanadate and upon a return to vanadate
      free conditions was investigated. External invertase secretion was inhibited by
      vanadate, as shown by a decrease in external invertase activity, an intracellular
      accumulation of small vesicles and a cytoplasmic accumulation of internal
      invertase. An aberrant appearance of the cell wall and defects in cellular
      surface growth, possibly linked to defects in secretion, were also observed.
      However, inhibition of the secretory pathway was not complete since the activity
      of another secreted enzyme, exoglucanase, increased in the presence of vanadate.
      Growth on vanadate was also accompanied by an enhancement of vacuolar
      proteolysis, as indicated by an increase in carboxypeptidase Y activity. However,
      these modifications were all reversible upon return to vanadate-free conditions,
      with the normalization process being complex and involving new and dramatic
      ultrastructural changes and activation of an autophagic mechanism. This mechanism
      is involved in the elimination/resorption of the observed vanadate-induced
      aberrant cell structures and/or sites involved in vanadate accumulation, a
      necessary prerequisite for restoration of conventional ultrastructure and
      metabolic functions.

PMID- 9782509
TI  - Bacterial chemotactic motility is important for the initiation of wheat root
      colonization by Azospirillum brasilense.
AB  - Bacteria of the genus Azospirillum are able to colonize plant roots. Using the
      beta-glucuronidase (GUS) reporter system, various Azospirillum mutants, including
      mutants affected in chemotactic motility or extracellular polysaccharide
      biosynthesis, were investigated for their capacity to initiate wheat root
      colonization at the root hair zones. Only non-flagellated mutants and a generally
      non-chemotactic mutant exhibited a strongly reduced colonization ability as
      compared to the wild-type. No role of the Azospirillum calcofluor-binding
      polysaccharide in primary wheat root colonization could be observed. This is the
      first report demonstrating directly, by using different motility mutants, the
      requirement of bacterial motility in the establishment of the Azospirillum-plant
      root association.

PMID- 9782510
TI  - Mutants of Rhizobium tropici strain CIAT899 that do not induce chlorosis in
      plants.
AB  - Type B strains of Rhizobium tropici induce severe foliar chlorosis when applied
      at planting to seeds of symbiotic host and non-host dicotyledonous plants. A Tn5
      induced mutant, designated CT4812, or R. tropici strain CIAT899 that was unable
      to induce chlorosis was isolated. Cloning and sequencing of the DNA flanking the
      transposon in CT4812 revealed that the Tn5 insertion is located in a gene similar
      to glnD, which encodes uridylyltransferase/uridylyl-removing enzyme in enteric
      bacteria. Two marker-exchange mutants with insertions in glnD also failed to
      induce chlorosis in bean (Phaseolus vulgaris) plants. The 5'-most insertion in
      glnD (in mutant strain ME330) abolished the ability of R. tropici to utilize
      nitrate as a sole carbon source, whereas a mutation in glnD further downstream
      (in mutant strain ME245) did not have an obvious effect on nitrate utilization. A
      gene similar to the Salmonella typhimurium virulence gene mviN overlaps the 3'
      end of the R. tropici glnD homologue. A mutation in mviN had no effect on the
      ability of CIAT899 to induce chlorosis in bean plants. Therefore the glnD
      homologue, but not mviN, appears to be required for induction of chlorosis in
      plants by R. tropici strain CIAT899. A high nitrogen: carbon ratio in the
      rhizosphere of bean plants also prevented R. tropici from inducing chlorosis in
      bean plants. Mutations in either the glnD homologue or mviN had no significant
      effect on root nodule formation or acetylene reduction activity. A mutation in
      mviN eliminated motility in R. tropici. The sequence data, the inability of the
      glnD mutant to utilize nitrate, and the role of the R. tropici glnD gene in
      chlorosis induction in plants, a process that is nitrogen regulated, suggest that
      glnD plays a role in nitrogen sensing in R. tropici as its homologues do in other
      organisms.

PMID- 9782511
TI  - A stomatin-like protein encoded by the slp gene of Rhizobium etli is required for
      nodulation competitiveness on the common bean.
AB  - Rhizobium etli strain TAL182 is a competitive strain for effective nodulation of
      beans. From this strain, a novel gene was isolated, slp, which is 669 bp in size
      and required for nodulation competition on the common bean. The slp knockout
      mutant of TAL182 is defective in nodulation competition, shows reduced growth in
      the presence of 200 mM NaCl, KCl or LiCl and is complemented by the cloned slp
      gene. The deduced amino acid sequence of slp shows 66-72% similarity to stomatin
      proteins of Homo sapiens, Mus musculus and Caenorhabditis elegans. Expression of
      slp in Escherichia coli from a T7 promoter shows a 26 kDa protein which cross
      reacts with human-stomatin-specific polyclonal antibody. Like the human stomatin
      protein, the slp-deduced protein, Slp, is very hydrophilic except for a single
      hydrophobic membrane-spanning domain. Among various bean-nodulating rhizobia, slp
      is present in R. etli, Rhizobium leguminosarum bv. phaseoli and Rhizobium tropici
      type A strains but is absent in R. tropici type B strains. It is also absent in
      Bradyrhizobium and several other Rhizobium spp.

PMID- 9782512
TI  - Glutamine biosynthesis and the utilization of succinate and glutamine by
      Rhizobium etli and Sinorhizobium meliloti.
AB  - Sinorhizobium meliloti 1021 and Rhizobium etli CE3 turn over nitrogen and carbon
      from glutamine to ammonium and CO2, respectively. Some of the ammonium released
      is assimilated back into glutamine, indicating that a glutamine cycle similar to
      that in Neurospora operates in Rhizobium. In addition, a previously unrecognized
      metabolic pathway in Rhizobium was discovered--namely, conversion of glutamine
      carbon to gamma-hydroxybutyric acid and beta-hydroxybutyric acid. Additionally,
      some of the 2-oxoglutarate derived from glutamine catabolism in Rhizobium is
      converted to succinate in glutamine-containing medium. Both S. meliloti 1021 and
      R. etli CE3 oxidize succinate preferentially over glutamine when provided with
      both carbon sources. In contrast to Sinorhizobium meliloti 1021 and Rhizobium
      etli CE3, an S. meliloti double mutant that lacks both glutamine synthetase (GS)
      I and II preferentially oxidizes glutamine over succinate when supplied with both
      substrates. GSII activity is induced in wild-type S. meliloti 1021 and R. etli
      CE3 grown in succinate-glutamine medium, and this enzyme participates in the
      cycling of glutamine-carbon and -nitrogen. On the other hand, GSII activity is
      repressed in both micro-organisms when glutamine is the only carbon source. These
      findings show that, in medium containing both glutamine and succinate, glutamine
      synthesis helps drive the utilization of succinate. When glutamine is in excess
      as an energy-providing substrate its synthesis is restricted, allowing for more
      effective utilization of glutamine as an energy source.

PMID- 9782513
TI  - Biosynthesis of triacylglycerol in the filamentous fungus Mucor circinelloides.
AB  - Lipid metabolism was studied in 2-d-old liquid cultures of Mucor circinelloides
      grown at 25 degrees C. Under these conditions, oil accumulated to 0.5 g l-1 with
      a gamma-linolenic acid content (gamma 18:3) of 60 mg l-1. The major labelled
      lipids in cultures incubated with [14C]acetate were triacylglycerol (TAG),
      phosphatidylcholine (PC) and phosphatidylethanolamine (PE). The proportion of
      label declined in the phospholipids and increased in TAG with time. [14C]18:1 and
      [14C]18:2 rapidly appeared in PC and PE and later accumulated in [14C]gamma 18:3.
      TAG-synthesizing capacity was greatest in the microsomal membrane fraction, which
      accumulated high levels of phosphatidic acid in the presence of glycerol 3
      phosphate and acyl-CoA substrates at pH 7.0. Further metabolism of phosphatidic
      acid to diacylglycerol and TAG was achieved by increasing the pH to 8.0.
      Lysophosphatidic acid: acyl-CoA acyltransferase (LPAAT) activity was particularly
      high and may have accounted for the rapid accumulation of phosphatidic acid in
      the membranes. The glycerol-3-phosphate: acyl-CoA acyltransferase (GPAAT) and
      LPAAT were non-specific for a range of saturated and unsaturated species of acyl
      CoA although the GPAAT showed a marked selectivity for palmitoyl-CoA and the
      LPAAT for oleoyl- and linoleoyl-CoA. gamma-Linolenic acid was detected at all
      three positions of sn-TAG and was particularly enriched at the sn-3 position. The
      preparation of active in vitro systems (microsomal membranes) capable of the
      complete biosynthetic pathway for TAG assembly may be valuable in understanding
      the assembly of oils in future transgenic applications.

PMID- 9782514
TI  - Intracellular chitinase gene from Rhizopus oligosporus: molecular cloning and
      characterization.
AB  - Multiple chitinases have been found in hyphae of filamentous fungi, which are
      presumed to have various functions during hyphal growth. Here it is reported, for
      the first time, the primary structure of one such intracellular chitinase, named
      chitinase III, from Rhizopus oligosporus, a zygomycete filamentous fungus.
      Chitinase III was purified to homogeneity from actively growing mycelia of R.
      oligosporus using three steps of column chromatography. Its molecular mass was
      43.5 kDa and the pH optimum was 6.0 when p-nitrophenyl N,N',N"-beta-D
      triacetylchitotrioside was used as a substrate. Chitinase III also hydrolysed
      chromogenic derivatives of chitobiose, but had no N-acetylglucosaminidase
      activity. The gene encoding chitinase III (chi3) was cloned using PCR with
      degenerate oligonucleotide primers from the partial amino acid sequence of the
      enzyme. The deduced amino acid sequence of chi3 was similar to that of bacterial
      chitinases and chitinases from mycoparasitic fungi, such as Aphanocladium album
      and Trichoderma harzianum, but it had no potential secretory signal sequence in
      its amino terminus. Northern blot analysis showed that chi3 was transcribed
      during hyphal growth. These results suggest that chitinase III may function
      during morphogenesis in R. oligosporus.

PMID- 9782515
TI  - Phylogenetic diversity of mesophilic and thermophilic granular sludges determined
      by 16S rRNA gene analysis.
AB  - The microbial diversity of two types of methanogenic granular sludge, mesophilic
      (35 degrees C) and thermophilic (55 degrees C), which had been treating
      sucrose/propionate/acetate-based artificial wastewater were compared. 16S rDNA
      clone libraries were constructed by PCR with a prokaryote-specific primer set,
      and partial sequencing of the clonal 16S rDNAs was conducted for phylogenetic
      analysis. Of 115 mesophilic granule and 110 thermophilic granule clones
      sequenced, 19 and 22%, respectively, were phylogenetically affiliated with the
      domain Archaea, and the remainder in each case were assigned to the domain
      Bacteria. Within the domain Archaea, the 16S rDNA clones in both libraries showed
      relatively close relationships with those of methanogens. Within the Bacteria, a
      major group represented in the mesophilic clone library was the delta subclass of
      the Proteobacteria (27%), in which high degrees of relatedness were observed
      between the clonal 16S rDNA sequences and those of previously identified
      syntrophic bacteria and sulfate-reducing bacteria. In contrast, in the
      thermophilic clone library, the Thermodesulfovibrio group (19%), the green non
      sulfur bacteria (18%) and the low G + C subclass of the Gram-positive bacteria
      (18%) were predominant. A significant difference between the two libraries was
      that no clone affiliated with the Proteobacteria was detected in the thermophilic
      clone library, whereas the Proteobacteria was detected in the thermophilic clone
      library, whereas the Proteobacteria was the most predominant group in the
      mesophilic clones. Thirty-six and 24 different sequences were found in the
      mesophilic and thermophilic clones, respectively, suggesting that the microbial
      diversity of the thermophilic granule was lower than that of the mesophilic
      granule.

PMID- 9782517
TI  - Theories about therapies are underdeveloped.

PMID- 9782516
TI  - Shigella and enteroinvasive Escherichia coli strains are derived from distinct
      ancestral strains of E. coli.
AB  - The differentiation between Shigella subspecies, and the phylogenetic position of
      Shigella clones within Escherichia coli clones was determined by analysis of
      restriction fragment length polymorphisms of rDNA (ribotyping). Seventy-five
      Shigella strains belonging to the four subspecies and 13 enteroinvasive E. coli
      (EIEC) strains were compared with the 72 E. coli strains of the ECOR collection,
      which have been classified into four phylogenetic groups (A, B1, B2 and D).
      Seventeen Shigella dysenteriae ribotypes, 12 Shigella flexneri ribotypes, 23
      Shiegella boydii ribotypes, 12 Shigella sonnei ribotypes and 13 EIEC ribotypes
      were identified following digestion with HindIII and EcoRI. Correspondence
      analysis of the data showed that S. boydii serotype 13 strains were distantly
      related to the other Shigella strains, and that S. sonnei and S. flexneri were
      distinct from S. boydii and S. dysenteriae. The ribotypes of Shigella and ECOR
      strains were indistinguishable, and S. sonnei, S. flexneri and most S.
      dysenteriae strains were closely related to phylogenetic group D, whereas S.
      dysenteriae serotype 1 strains belonged to phylogenetic group B1, and S. boydii
      strains were evenly distributed between the two groups. The Shigella strains were
      distantly related to group B2, which contains E. coli strains frequently
      implicated in extra-intestinal infections in humans. In contrast, the 13 EIEC
      strains were more widely distributed between phylogenetic groups B1, A and B2.
      Thus, there was no primordial Shigella species and Shigella and EIEC strains are
      derived from different ancestral strains.

PMID- 9782519
TI  - Falls reported among elderly Norwegians living at home.
AB  - BACKGROUND AND PURPOSE: Norway has the highest reported incidence of hip
      fractures in western Europe. Little is known about the epidemiology of falls in
      Norway where the winter season is long and dark. The objective of this work was
      to study reported falls and their consequences among elderly Norwegians living at
      home. METHODS: A cross-sectional design was used for the study. Interviews were
      performed in the homes of 431 subjects, aged 67-97 years, living at home.
      Information on falling was gathered through six questions: whether the subject
      had fallen during the last six months, and if so, how many falls they had, where
      the last fall occurred, its perceived reason, the activity the subject had been
      engaged in when the fall occurred, and the resulting injury. RESULTS: In all,
      24.1% of subjects reported falling during the last six months, and 9.5% had
      suffered more than one fall. Falls were most frequently linked to external events
      (63.1%). Outdoor falls were more frequent (59.0%; 95% CI = 51.2-82.0) than indoor
      falls. Older subjects were associated with more frequent indoor falls (p < 0.05),
      but gender was not significant. Fifty-one per cent of subjects had fallen while
      walking and 53% had suffered an injury from the last fall. In 13.4% of the women
      and 16.2% of the men, the last fall had resulted in a fracture. CONCLUSIONS:
      Compared to the results of other studies from industrialized Western countries, a
      similar crude fall rate, similar frequency and similar type of injury were found.
      However, in contrast to other studies, no gender difference was observed with
      regard to falling, place of falling and fracture rate.

PMID- 9782518
TI  - Functional capacity and early radiographic osteoarthritis in middle-aged people
      with chronic knee pain.
AB  - BACKGROUND AND PURPOSE: In order to improve the physiotherapeutic treatment of
      patients with long-standing knee pain, it is important to identify osteoarthritis
      (OA) of the knee at an early stage. The aim of the present study was to test the
      value of single functional measurement variables with the focus on the lower
      extremities for the association to early radiographic signs of OA of the knee.
      The classification by Ahlback grade I (joint space narrowing) was used in a
      cohort of 204 individuals aged 35-54 years with long-standing knee pain. METHODS:
      The following five selected tests were employed: three tests of static and
      dynamic balance (Balance I-III); one test of muscle strength (one-leg-rising
      test, OLR); and one test of walking ability (time for walking 300 m indoors).
      Odds ratios (ORs) were calculated with a 95% confidence interval. RESULTS AND
      CONCLUSIONS: Results revealed that the selected tests of functional capacity due
      to rather low sensitivity (0.15-0.81), specificity (0.21-0.86) and inconclusive
      odds ratios (0.78-1.62) are probably of limited value as assessment tools to find
      radiographic knee OA in a younger population with mild OA. However, it is also
      possible to conclude that in middle-aged individuals with chronic knee pain, the
      diagnosis of radiographic OA is not related to the functional capacity as
      measured in the present study.

PMID- 9782520
TI  - Asthmatic patients' views of a comprehensive asthma rehabilitation programme: a
      three-year follow-up.
AB  - BACKGROUND AND PURPOSE: Twenty-one asthmatic patients aged 27-59 years, with mild
      to moderate asthma, participated in a 10-week group rehabilitation programme
      covering physical training and theoretical and practical education in medication,
      self-management strategies and physiotherapy. This study was undertaken
      retrospectively to investigate (1) the patients' reasons for joining the
      programme, (2) their experiences of the programme, and (3) their ways of coping
      with disease-related problems before joining and three years after completion of
      the programme. METHODS: Patients were followed up every six months for three
      years and were interviewed after the three years. The semi-structured interviews
      were tape-recorded, transcribed and revised. RESULTS: The life-situation of most
      of the patients before the 10-week programme was characterized by helplessness at
      exacerbations, anxiety/insecurity about medications and their side-effects,
      and/or concern about future health. More than half of the subjects felt physical
      limitations in daily life or when exercising. All wished to increase their
      knowledge of asthma by joining the programme, but only nine patients expected
      asthma improvement. The experience that they were able to carry out physical
      exercise to a maximal intensity and that physical training improved their asthma,
      with increased knowledge about medications were mentioned by all as the most
      valuable effects of the programme. Moreover, most patients emphasized their
      increased ability in self-management strategies (stress reduction and breathing
      technique). The increased knowledge and improved practical skills contributed to
      a better life-situation after the rehabilitation. After the three years virtually
      all the patients' lives were characterized by improved self-management, increased
      physical activity and a sense of security. Almost half of them expressed a wish
      to take responsibility for the disease. CONCLUSIONS: In addition to medical
      therapy and education, physical training and techniques for relaxation and
      breathing should form part of the treatment of asthma.

PMID- 9782521
TI  - Recovery of walking function in stroke patients after minimal rehabilitation.
AB  - BACKGROUND AND PURPOSE: Independent walking function is a highly desired goal
      amonst stroke victims, and has been well reported in Western literature. However,
      few studies have investigated the recovery of gait following stroke in Third
      World countries, where rehabilitation is often minimal or non-existent. METHODS:
      A descriptive survey, using a structured questionnaire, was conducted on stroke
      victims, 12-14 weeks post-discharge from the Chris Hani Baragwanath Hospital,
      Soweto, South Africa. Although the questionnaire included a number of aspects of
      impairment, disability and handicap, this paper only reports on the recovery of
      walking function. RESULTS: A total of 361 patients were screened initially. Only
      54 fulfilled all inclusion criteria, 38 (70%) were over 50 years of age and 16
      (30%) were aged under 50 years. The average length of stay in hospital of the
      older group was eight days, and in the younger group, 11.5 days. All 54 subjects
      interviewed were able to walk prior to their stroke. Twelve to fourteen weeks
      postdischarge, 23 (66%) subjects in the older group and all (100%) of the younger
      group said they could walk. Half of the older group and nearly all of the younger
      group could walk outside their homes, unassisted and without appliances. One
      third of the subjects experienced knee pain during walking, but only a small
      percentage said that this pain prevented them from walking. The ability to catch
      a taxi in Soweto was used as a measurement of the handicap of gait. Twenty (54%)
      older group subjects and five (31%) of the younger group never caught a taxi.
      CONCLUSIONS: Although the recovery of gait in these subjects appears to have been
      good, the results cannot be extrapolated to the stroke population in general due
      to the stringent selection criteria of the study. Further studies are required to
      acquire a broader cross-section of the stroke population, including longer follow
      up periods to gain insight into the continuation of walking function. This
      information is necessary in order to plan effective and appropriate
      rehabilitation services.

PMID- 9782522
TI  - A survey of UK manual therapists' practice of and attitudes towards manipulation
      and its complications.
AB  - BACKGROUND AND PURPOSE: Little is known about the practice of manipulation by UK
      physiotherapists. This study was conducted to discover current practice of, and
      attitudes towards, manipulation among UK manipulative therapists. METHODS: A
      postal questionnaire was sent to 300 UK manipulative therapists who were members
      of two professional associations representing differing approaches to manual
      therapy: the Society of Orthopaedic Medicine (SOM) and the Manipulation
      Association of Chartered Physiotherapists (MACP). RESULTS: A 50% response rate
      was achieved and 129 respondents identified themselves as 'users' of
      manipulation. Anxiety about possible complications was a prominent reason adduced
      by 'non-users' and 'partial users' for their avoidance of manipulative
      procedures. The thoracic spine was the region most often manipulated, followed by
      the lumbar spine. Nineteen per cent of users had encountered complications from
      manipulation, which were most common in the cervical region and were
      predominantly non-serious. The majority of SOM members and a minority of MACP
      members used generalized cervical rotary manipulations--thought by some to be
      potentially dangerous. Attitudes to manipulation were generally positive,
      although overall respondents were uncertain as to whether its benefits outweighed
      its risks. Members of the SOM emerged as more frequent users of manipulation and
      as less conservative in their attitudes to certain aspects of manipulation.
      CONCLUSIONS: Allowing for possible under-reporting or other response biases,
      spinal manipulation emerged as a relatively safe and widely practised technique
      among this sample.

PMID- 9782523
TI  - Treatment of torticollis in infancy by manual pressure applied over the parasacro
      coccygeal structures.

PMID- 9782524
TI  - Recovery of walking function in stroke patients after minimal rehabilitation.

PMID- 9782525
TI  - Nitrite production does not always reflect nitric oxide synthesis by isolated
      glomeruli.
AB  - The goal of this paper was the measurement of nitric oxide (NO) production in
      isolated rat glomeruli using two different techniques. NO production was detected
      directly by a NO-specific electrode and the results were compared with data
      measured by the Griess reaction, an indirect index to evaluate NO production. The
      NO production, determined by both techniques, was dependent on the number of
      glomeruli. Pretreatment with Nw-nitro-L-arginine methyl ester, an inhibitor of
      the NO synthesis, reduced the NO concentration detected by the NO-sensor, but
      increased the NO2-concentration (when both results where compared with glomeruli
      without treatment). Preincubation with 1 mg/ml of Escherichia coli
      lipopolysaccharide significantly enhanced both NO and NO2-concentrations.
      Therefore, the present study provides direct evidence of NO generated in isolated
      glomeruli under physiological conditions and demonstrates that the measurement of
      NO2- by the Griess reaction, is not always an adequate technique to evaluate the
      actual NO production.

PMID- 9782526
TI  - Impact of ischemia-reperfusion injury on dimensional changes of hepatic
      microvessels.
AB  - Dimensional alteration of hepatic microvessels was demonstrated during
      reperfusion after normothermic hepatic ischemia. Using a specially designed cover
      glass, it was possible to relocate selected sites of observation and microvessels
      repeatedly throughout the whole reperfusion time. Twenty minutes of hepatic
      ischemia resulted in a decrease of sinusoidal diameter (mean +/- SEM; 10.0 +/-
      0.3 microns at baseline, 8.2 +/- 0.2 microns after ischemia) and diameter of
      postsinusoidal venules (26.4 +/- 1.2 at baseline, 23.0 +/- 1.0 after ischemia).
      In the control group (no ischemia induced) no changes of these parameters were
      observed. Thus, the reduction of hepatic microvascular cross section was present
      during the early phase of reperfusion. Hepatic dysfunction was characterized by
      increased serum activity of liver enzymes and reduction of bile flow in the
      ischemia-exposed animals. It has been suggested that postischemic dimensional
      microvascular changes are involved in postischemic liver dysfunction.

PMID- 9782527
TI  - Simultaneous detection of cell volume and intracellular pH in isolated rat
      duodenal cells by confocal microscopy and BCECF.
AB  - The combination of confocal laser scan microscopy and the pH-sensitive
      fluorescent dye BCECF allowed us to record simultaneously intracellular pH, cell
      viability and relative cell volume. pH was measured by using the pH-sensitive
      excitation wavelength at 488 nm and the pH-independent excitation wavelength at
      442 nm to obtain ratio images. Cell volume was traced by measuring fluorescence
      dye concentration at 442 nm. Isolated villus tip rat duodenal enterocytes were
      exposed to 20 mM NH4Cl, sodium free, or 1 mM amiloride buffer. Sodium free buffer
      and amiloride buffer acidified the cells. Cell volume did not change in sodium
      free buffer, or NH4Cl exposure, but amiloride led to an increase in cell volume
      of 20%. After acidification of the duodenal cells, amiloride buffer increased
      cell volume by almost 50%. These studies revealed that cell volume regulation
      during pH changes in short-living cells could easily be detected by confocal
      microscopy and BCECF.

PMID- 9782528
TI  - Lung flooding--a new method for complete lung sonography.
AB  - A sonographic examination of the lung has so far been impossible because of sound
      reflection. In conjunction with video-assisted thoracoscopic surgery, lung
      sonography would be helpful to make up for the lack of direct palpation. Animal
      experiments with pigs were performed to find out whether lung sonography becomes
      possible following bronchoalveolar flooding with a suitable liquid. The lung was
      filled with whole electrolyte solution through the left leg of a double-lumen
      endotracheal tube after resorption atelectasis (method 1) or compressive
      atelectasis (method 2). As an alternative, liquid perfluorocarbon was used
      (method 3). Under atelectasis, the lung thus flooded was investigated by
      ultrasound applied transpleurally and endobronchially. The first results proved
      that lung flooding is possible if certain prerequisites are fulfilled.
      Perfluorocarbon flooding led to total sound absorption which prevented
      sonography, whereas flooding with whole electrolyte solution made complete lung
      sonography possible, making visible the intrapulmonary vessels, bronchi and
      peribronchial lymphatic nodes. Measurements proved that the unilateral flooding
      caused no significant changes in the arterial and central venous pressure nor in
      transcutaneous oxygen saturation.

PMID- 9782529
TI  - Inhibitory effect of Hesperidin on tumour initiation and promotion in mouse skin.
AB  - A flavonoid, Hesperidin was evaluated for its ability to inhibit tumour
      initiation by a polycyclic aromatic hydrocarbon and tumour promotion by a phorbol
      ester in the skin of CD-1 mice. Subcutaneous application of Hesperidin did not
      inhibit 7,12-dimethylbenz(a)anthracene-induced tumour initiation but did inhibit
      12-O-tetradecanoyl-13-phorbol acetate-induced tumour promotion. Results provide
      evidence for a potential chemopreventive activity of Hesperidin.

PMID- 9782530
TI  - Blood flow of the submandibular gland in sodium-depleted and -loaded rats: effect
      of nitric oxide synthase inhibition.
AB  - The present investigations were designed to study the hemodynamic effects of
      different sodium diets in the submandibular gland of rats with or without nitric
      oxide (NO) synthesis inhibition. Experimental animals were kept on: (1) standard
      chow and tap water ad libitum (normal group, N), or (2) wheat and distilled water
      ad libitum for 4 weeks (sodium-depleted animals, SD), or (3) standard chow and
      saline ad libitum for 4 weeks (sodium-loaded animals, SL). NO synthase was
      inhibited by N omega-nitro-L-arginine-methyl-ester (L-NAME, 10 mg/kg per day) in
      the last week. The rats were anesthetized, and blood pressure, cardiac output
      (Stewart-Hamilton's principle) and blood flow (BF) of the submandibular gland
      (Sapirstein's technique) were determined. High sodium intake resulted in a 47%
      increase of glandular BF as compared to BF measured in the control group. In all
      groups L-NAME decreased BF (ml/min per 100 g gland) as compared to those of rats
      with no L-NAME treatment (N: 76.4 +/- 15.4 vs. 56.0 +/- 11.6, P < 0.05; SD: 71.0
      +/- 17.7 vs. 56.2 +/- 15.1, n.s.; SL: 112 +/- 29.4 vs. 66.9 +/- 18.4, P < 0.001),
      whereas the vascular resistance (VR, mm Hg x ml-1 x s x kg-1) increased (N: 11.0
      +/- 2.3 vs. 17.5 +/- 4.1, P < 0.001; SD: 11.0 +/- 2.7 vs. 17.0 +/- 4.2, P < 0.01;
      SL: 8.5 +/- 2.4 vs. 14.9 +/- 4.6, P < 0.001). The increase in VR after L-NAME
      treatment was 64% in normal, 55% in sodium-depleted and 75% in sodium-loaded
      rats. Our results suggest that NO takes part in the regulation of vascular
      resistance and BF in the submandibular gland. Sodium load itself increases BF of
      the submandibular gland and this phenomenon may partly be mediated by NO.

PMID- 9782531
TI  - Nitric oxide synthesis is increased in patients with systemic lupus
      erythematosus.
AB  - Nitric oxide (NO) is believed to have a role in the inflammatory process. NO
      production was measured in 26 patients with systemic lupus erythematosus (SLE)
      and 20 healthy volunteers, using spectrophotometrically determined serum nitrite
      and citrulline as surrogate markers. Both nitrite and citrulline levels were
      significantly higher in patients with SLE than in controls (P < 0.001). Twelve
      and 10 patients, respectively, with SLE had nitrite and citrulline levels that
      were two standard deviations higher than the mean level of controls. These
      patients had a significantly higher measure of disease activity (SLE Disease
      Activity Index). These data show that there is increased NO production in SLE and
      that it may serve as a marker for disease activity.

PMID- 9782533
TI  - Adhesion molecule expression in erythema nodosum-like lesions in Behcet's
      disease. A histopathological and immunohistochemical study.
AB  - Behcet's (BD) is a systemic inflammatory disease with histological evidence for
      vasculitis. Leucocyte-leucocyte and leucocyte-endothelial cell interactions are
      critical in inflammatory reactions that are influenced by the expression,
      activation and shedding of adhesion molecules. We investigated the expression of
      some adhesion molecules (E- and L-selectin, VLA-4, ICAM-1, PECAM-1, VCAM-1 and
      CD18 and CD11c chains of beta-2 integrins) on endothelial and inflammatory cells
      by immunohistochemistry on cryostat sections of erythema nodosum lesions taken
      from 15 patients with BD and 12 patients with erythema nodosum of unknown cause.
      Hematoxylin-eosin stained sections of all specimens were also assessed. The major
      histopathological findings were perivascular mononuclear cell infiltration and
      secondary vasculitic changes with no difference between the two groups (P >
      0.05). However, the frequency of thrombophlebitis was higher in BD (P < 0.001).
      Endothelial and inflammatory cell adhesion molecule expression did not show any
      significant difference between groups (P > 0.05). Although VCAM-1 expression and
      intensity on endothelial cells of BD patients seemed to be lower, this did not
      reach statistical significance (P = 0.056). We concluded that subcutaneous
      thrombophlebitis is an important feature of erythema nodosum like lesions in BD,
      which is almost impossible to understand by physical examination alone.
      Colchicine, which is known to have some influence on adhesion molecules, might
      have affected our results, as these showed no significant difference regarding
      adhesion molecules between the two groups.

PMID- 9782532
TI  - Osteoporosis in juvenile systemic lupus erythematosus: a longitudinal study on
      the effect of steroids on bone mineral density.
AB  - Peak bone mass is an important determinant of future bone mass and of the risk of
      osteoporosis and subsequent fractures. Although some information concerning bone
      mineral density (BMD) in adults affected with systemic lupus erythematosus (SLE)
      is available, few data on children and adolescents have been reported. Many
      variables, such as duration and activity of the disease, reduced sun exposure,
      and steroid therapy have been suggested as risk factors in the pathogenesis of
      osteoporosis in SLE. In this study, we longitudinally evaluated, by dual energy X
      ray absorptiometry (DEXA), the BMD of 20 young patients affected with juvenile
      SLE (JSLE), in order to establish the degree of osteoporosis and the influence of
      steroid treatment, among other clinical variables. At baseline, the mean BMD in
      JSLE patients was 0.978 g/cm2 and in controls 1.038 g/cm2 (P = 0.31). At 1 year
      (time 2), this value became 0.947 g/cm2 in JSLE children; the mean individual
      difference was 0.28 g/cm2 (3.4%). Only in those patients aged 19-25 years BMD was
      significantly lower than in controls, both at baseline and at time 2. Considering
      the steroid treatment, no significant difference between the two groups was found
      either at baseline or at time 2; however, the mean yearly BMD loss in the steroid
      patients was 0.031 g/cm2 (3.5%) vs. 0.005 g/cm2 (0.5%) in those who had not taken
      steroids. A significantly inverse correlation between BMD and the cumulative
      dosage of corticosteroids has been detected. BMD produced a significantly inverse
      correlation to the cumulative dosage of corticosteroids; no significant
      correlation has been found between BMD and disease activity or duration.

PMID- 9782534
TI  - Management of cutaneous lupus erythematosus with low-dose methotrexate:
      indication for modulation of inflammatory mechanisms.
AB  - There is no consensus about an effective and safe treatment for patients with
      cutaneous lupus erythematosus (LE) who are refractory to antimalarials and/or low
      dose oral glucocorticosteroids. Therefore, we retrospectively analyzed the
      clinical data and laboratory findings of 12 patients who received weekly
      administrations of 10-25 mg methotrexate (MTX). Previous treatment with
      antimalarials and/or glucocorticosteroids was not effective or had to be
      withdrawn because of side effects. Of 12 patients, ten showed improvement of
      their skin lesions; two patients did not respond to low-dose MTX; two patients
      cleared rapidly, and five other patients had long-lasting remissions of 5-24
      months after stopping MTX treatment. A reduction of circulating autoantibodies
      was detected in five patients. In all patients, MTX was well tolerated
      subjectively and objectively. Weekly low-dose MTX is useful for the treatment of
      cutaneous LE, particularly in those cases which need long-term treatment and/or
      do not respond to standard therapeutic regimens.

PMID- 9782535
TI  - Association of IgA anti-dsDNA antibodies with vasculitis and disease activity in
      systemic lupus erythematosus. SLE Study Group.
AB  - Previously it has been suggested that the presence of antibodies against dsDNA of
      the IgA class may define a subset of systemic lupus erythematosus (SLE) patients
      suffering from nephritis and arthritis. Therefore, these autoantibodies were
      measured in sera of 352 patients with SLE, 81 blood donors, and 189 patients with
      rheumatoid arthritis using a new ELISA based on human recombinant dsDNA as
      antigen. IgA anti-dsDNA antibodies were found in 19.9% of the sera from patients
      with SLE, but in none of the sera from 81 normal controls and 189 patients with
      rheumatoid arthritis. The association of these autoantibodies with 31 clinical
      and 36 laboratory parameters was calculated. IgA anti-dsDNA antibodies were found
      to be associated with parameters of disease activity such as elevated erythrocyte
      sedimentation rate and consumption of complement component C3, and the clinical
      parameters vasculitis, with necrosis and erythema, but not with nephritis and
      arthritis. Therefore, IgA anti-dsDNA antibodies define a subset of SLE patients,
      and monitoring of IgA anti-dsDNA antibodies may be helpful as a prognostic
      parameter in patients with SLE.

PMID- 9782536
TI  - Characterization of the macromolecular components of the articular cartilage
      surface.
AB  - The intact surface of articular cartilage is a highly organized structure
      composed of a variety of macromolecules. The studies reported here deal with a
      partial characterization of the non-covalently bound components of the outermost
      layer of articular cartilage. Normal bovine and human cartilage articular
      surfaces were extracted for 5 min with 4-M guanidine HCl solution. Analysis and
      quantitation of small proteoglycans in the extract were carried out by PAGE
      (polyacrylamide gel electrophoresis), Western blot, and radioimmunoassays. The
      present studies indicate that the major proteins extracted from the articular
      surface of bovine and human cartilage are the collagen-binding small
      proteoglycans designated as fibromodulin and albumin. Fibronectin, decorin, and
      biglycan were also detected in smaller amounts. Immunoblotting of the surface
      material developed with a monoclonal antibody with keratan sulfate specificity
      confirmed the presence of fibromodulin coinciding with the major protein band of
      approximately 70-100-kDa molecular mass. Gel filtration chromatography of the
      surface material confirmed the previous results. Additional in vitro assays
      showed that the collagen-binding material extracted from the cartilage surface
      contained the small proteoglycans. Anti-human fibromodulin antibodies bound in
      significantly greater amounts to the intact articular surfaces than to cut
      surfaces of normal human cartilage. It is concluded that small, non-aggregating
      proteoglycans constitute the major proteoglycan species non-covalently bound to
      macromolecules at the articular surface of cartilage partially responsible for
      the interference of anti-collagen type II antibody binding and for the inhibition
      of cell adhesion to the intact surface.

PMID- 9782537
TI  - Myositis of small foot muscles.
AB  - Idiopathic focal myositis is a rare clinical entity and is mostly localized in
      the neck and thigh muscles presenting as a pseudotumor. We describe a 49-year-old
      patient with inflammation restricted to the small muscles of one forefoot.
      Systemic disease was not present and progression to polymyositis did not occur
      within 2 years of follow-up. The myositis improved promptly after initiation of
      immunosuppressive therapy with corticosteroids and azathioprine. This unusual
      location of focal myositis has not been previously reported.

PMID- 9782538
TI  - Quality indicators in spinal cord injury care: a Swedish collaborative project.
      The Swedish Spinal Cord Injury Council 1998.

PMID- 9782539
TI  - Normal variability of postural measures: implications for the reliability of
      relative balance performance outcomes.
AB  - The reliability of outcome measures obtained using the Balance Master and the
      limits of stability in anterior, posterior, and lateral directions were evaluated
      in 70 healthy subjects aged 20 to 32 years. Data relating to static sway and the
      ability to shift the centre of gravity to preset targets were collected on three
      occasions one week apart. The centre of gravity position and limits of stability
      were determined over three trials and data converted from a relative reference
      system to absolute displacements from vertical. Intraclass correlation
      coefficients revealed fair to poor reliability of static and dynamic sway
      measures (coefficients < or = 0.55) and excellent reliability of limits of
      stability measures and the position of the centre of gravity (coefficients > or =
      0.75). The variability in outcome measures from tests which do not maximally
      challenge the postural control system may be a hallmark of normal balance
      performance. Further, the intersubject variation in resting centre of gravity
      position and in limits of stability supports the use of absolute performance
      measures as the interpretive value of data expressed relative to standard norms
      is limited.

PMID- 9782540
TI  - Subacute and chronic low back pain. Reliability and validity of a Swedish version
      of the Roland and Morris Disability Questionnaire.
AB  - The purpose of this study was to investigate test-retest reliability and
      concurrent validity of a Swedish version of the Roland and Morris Disability
      Questionnaire (RM-Sw), and to describe demographic factors in patients with low
      back pain of at least 4 weeks' duration seeking outpatient physical therapy
      treatment in primary care settings. Seventy-two patients participated in the
      study. The intraclass correlation coefficient for a one-week test-retest interval
      was 0.88. There was moderate positive correlation with measures of perceived
      disability (r = 0.64, p < 0.001; r = 0.69, p < 0.001) and pain severity (r =
      0.54, p < 0.001), and low negative correlation with measures of perceived life
      control (r = -0.32, p < 0.01) and general activity (r = -0.27, p < 0.05). Gender,
      education and occupation were only moderately related to RM-Sw scores, explaining
      14% of the variance in the scores. It is concluded that RM-Sw is a reliable and
      valid measure of functional ability in low back pain.

PMID- 9782541
TI  - Treatment of emotionalism with fluoxetine during rehabilitation.
AB  - Emotionalism (emotional lability) is a common but distressing phenomenon that
      occurs frequently in individuals suffering cerebral vascular accidents and other
      brain diseases. Patients with emotionalism sometimes embarrass their families and
      themselves, becoming socially disabled despite normal physical function. At its
      worst, emotionalism interferes with rehabilitation programs, delays progress and
      sometimes makes these programs impossible. This paper reports the effect of
      fluoxetine in treating three patients with persistent emotionalism (2 cases
      following cerebrovascular accidents, 1 case following encephalitis). All 3
      patients demonstrated dramatic improvement in emotionalism within 6 days of
      treatment. The severity, frequency and duration of each episode were reduced
      greatly. The treatment improved the effectiveness of the rehabilitation program,
      relieved patient and family embarrassment, and enabled patients to resume rapidly
      their previous lifestyle patterns. All patients reached the functional goals
      planned prior to the onset of rehabilitation. We conclude that fluoxetine is
      highly effective in treating the symptoms of emotionalism in all patients, and
      allows for recovery of both physical and social function.

PMID- 9782542
TI  - Properties of person hoist spreader bars and their influence on sitting/lifting
      position.
AB  - The purpose of this study is to analyse mechanical lifts with regard to how the
      spreader bar design, e.g. frontal length, height and sagittal depth, affects
      sitting positions and safety during lift and transfer. The seven spreader bars
      available on the Swedish market had two-point to four-point suspensions. Twelve
      subjects were photographed individually sitting in each of three types of sling:
      divided, one-piece with divided leg support, and one-piece. All the slings had
      significant effects on all specific sitting aspects. However, the spreader bar
      design only affected the sitting position in the hoist. A long (0.62 m) spreader
      bar gave a relatively upright sitting position. A deep (0.18 m) spreader bar gave
      a backward inclination. For all specific sitting aspects, there was a significant
      interaction between slings and spreader bars. This study demonstrates that the
      design of the spreader bar, as well as that of the sling, is of decisive
      importance for the sitting position during lifting.

PMID- 9782543
TI  - Long-term follow-up of conservatively treated chronic tennis elbow patients. A
      prospective and retrospective analysis.
AB  - This study aimed to assess the long-term outcome of progressive exercise and
      local pulsed ultrasound in the treatment of 30 chronic tennis elbow patients (2
      men, 18 women, mean age 42.3 years). The patients were originally randomised into
      1) four-step progressive exercise (EX, n = 16) and 2) local pulsed ultrasound
      (US, n = 14) treatment groups. Before the beginning of the treatment, the groups
      were similar in terms of pain scores, sick-leave days and duration of symptoms.
      The patients underwent an 8-week treatment intervention. Long-term follow-up
      evaluation of the patients was performed 1) prospectively using a pain
      questionnaire on VAS and pain drawings classified into 5 categories, and 2)
      retrospectively with a postal questionnaire (which was sent to the patients to
      fill in. Sick-leave days, medical and physiotherapy visits, operations, early
      retirements and job relocations were inquired in the postal questionnaire. The
      diagnosis-related sick-leave days of the patients were collected from the
      Database of the Social Insurance Institution of Finland and the number of
      operations from the local hospital register. Twenty-three patients (12 in the EX
      group and 11 in the US group) responded. The mean follow-up time was 36 months.
      After the treatment the patients in the EX group needed significantly less
      physiotherapy (p = 0.02), fewer medical consultations (p = 0.005) and other
      treatments and had fewer sick-leave days (p = 0.005) than before the treatment
      intervention. The patients in the US group had after the treatment intervention
      more 17 medical visits (ns), 291 sick-leave days (ns) and less 95 physiotherapy
      visits (ns) than before the treatment. Eight patients (67%) in the EX group and 5
      (45%) in the US group still held their previous job, while two patients in the US
      group, but none in the EX group were absent from work because of the tennis elbow
      syndrome. The patients in the EX group reported significantly lower pain scores
      on VAS than those in the US group. The mean pain drawing category was 1.5 in the
      EX group and 2.7 in the US group (p = 0.008). All the pain scores and pain
      drawing categories in the EX group had changed to be significantly better than in
      the US group, where only pain under strain had significantly improved. Because of
      resistant symptoms, 5 patients were operated in the US group and one in the EX
      group. Neither spontaneous healing, nor self-limiting of the disorder were noted
      during the follow-up period. The progressive exercise evaluated in this study
      showed beneficial long-term effects compared to ultrasound treatment in terms of
      pain alleviation and working ability, and the functional overall condition of the
      exercise patients was also better. Exercise may be able to prevent chronicity and
      should hence be tried and recommended.

PMID- 9782544
TI  - Blood redistribution and circulatory responses to submaximal arm exercise in
      persons with spinal cord injury.
AB  - The purpose of this study was to evaluate responses to submaximal arm exercise
      (20%, 40%, and 60% of peak power output) using four conditions to support the
      circulatory redistribution in persons with spinal cord injury (SCI). Five males
      with tetraplegia (TP) and four males with paraplegia (PR) exercised 1) sitting,
      2) supine, and 3) sitting with the addition of a) an anti-gravity suit (anti-G),
      b) elastic stockings and abdominal binder, and c) functional electrical
      stimulation of the leg muscles. Compared to sitting, the following significant
      changes were observed: in the supine position, heart rate (HR) decreased (PR: 104
      vs 118 b/min, TP: 76 vs 92 b/min) and stroke volume (SV) increased (PR: 132 vs
      116 ml, TP: 96 vs 83 ml). The anti-G suit induced a decrease in heart rate (PR:
      104 vs 118 b/min, TP: 87 vs 92 b/min) and a decrease in oxygen uptake (VO2) in
      PR. Stockings only affected TP, i.e. a decrease in heart rate with 5 b/min and an
      increase in stroke volume with 13 ml/beat. Functional electrical stimulation
      produced an increase in VO2 (PR: 1.00 vs 0.95 l/min, TP: 0.68 vs 0.53 l/min) and
      a rise in stroke volume in TP. Results indicate that the methods employed to
      support the circulatory redistribution have different working mechanisms and, in
      addition, that the effects are different for TP and PR probably because of
      differences in active muscle mass, sympathetic impairment and blood pressure
      values.

PMID- 9782545
TI  - Relative EMG levels in training exercises for abdominal and hip flexor muscles.
AB  - The main purpose of our study was to compare systematically EMG levels in sub
      maximal training exercises for the trunk and hip flexor muscles with those
      voluntarily attainable in corresponding situations. Six healthy subjects
      performed three types of standardized training exercises, whose static positions,
      movement velocity and range of motion were reproduced during maximal voluntary
      isokinetic strength tests. EMG was recorded with wire electrodes from the iliacus
      muscle and with surface electrodes from the rectus femoris, sartorius, rectus
      abdominis, obliquus externus and internus muscles. The relative EMG values
      demonstrated a task dependency which could differ between individual muscles. The
      maximal voluntary activation levels were relatively constant across conditions.
      Exceptions were present, particularly for the rectus femoris and iliacus muscles.
      These findings highlight the consequences of using different methods of
      normalizing EMG. The relative EMG values presented may serve as guidelines when
      selecting training exercises for specific trunk and hip flexor muscles in sports
      and rehabilitation.

PMID- 9782546
TI  - Widespread musculoskeletal chronic pain associated with smoking. An
      epidemiological study in a general rural population.
AB  - Data on smoking and pain symptoms from a random sample (n = 1806) of a general
      population were used to evaluate the association between chronic pain at various
      locations and smoking. In both genders current smoking was associated with
      reports of increased pain in low back, neck and with multiple locations. In a
      multiple logistic regression analysis current smoking was associated with an
      increase in widespread chronic musculoskeletal pain (OR 1.60, CI 1.04-2.46, in
      relation to non-smokers) and chronic low back pain (OR 1.58, CI 1.13-2.20, in
      relation to non-smokers). A dose-response relationship was found between the
      daily cigarette consumption and the prevalence of chronic low back pain. Smoking
      is associated not only with low back pain but also with chronic widespread
      musculoskeletal pain. No conclusive decrease in pain prevalence was found after
      quitting smoking. Further studies are necessary to elucidate an aetiologic
      relationship between smoking and chronic pain.

PMID- 9782547
TI  - [Idiopathic primary hyperaldosteronism: significance of functional diagnosis].
AB  - Primary aldosteronism is a rare cause of hypertension caused by increased
      aldosterone secretion. The two essential stimuli for aldosterone production,
      potassium and angiotensin II, tend to be low. At a time when imaging procedures
      are becoming more common, more patients are being found with adrenal masses, and
      patients with incidentalomas and low renin hypertension could be considered as
      candidates for surgery. Apart from an appropriate work-up for the diagnosis of
      primary aldosteronism, the differential diagnosis between unilateral adenoma and
      idiopathic ("hyperplasia") hyperaldosteronism is relevant for the choice of
      therapy. Based on data from the literature and four patients we observed as
      outpatients in 1997, we suggest that a properly conducted and carefully
      interpreted postural stimulation test can be useful in identifying patients who
      are successfully treated by drugs.

PMID- 9782548
TI  - [DNA replication: mechanism and significance for general practice].
AB  - The maintenance of genetic information in a cell is ensured by essential
      macromolecular events called DNA replication and DNA repair. The cell possesses
      many control mechanisms that allow the optimal strategy under extreme
      physiological conditions. A cell that is in the process of replicating its DNA
      and faces a genotoxic stress such as UV-damage, X-ray damage and influences of
      mutagens will turn off DNA replication and instead turn on DNA repair mechanisms.
      We have learned in the last three years that in all these processes identical DNA
      synthetic enzymes are involved. They are, however, coordinated to the actually
      required metabolic events through a ring-shaped protein called proliferating cell
      nuclear antigen (PCNA). Exact knowledge of these protein-protein interactions
      will eventually open up novel therapeutic strategies against cancer.

PMID- 9782549
TI  - [Ethical aspects of heart transplantation].
AB  - Since the very beginning of organ transplantation, ethical considerations have
      been regularly discussed. However, all important religions support
      transplantation. On the donor side there is continuous argument on the definition
      of brain death. The legal approach in determining whether explantation of organs
      is allowed or not is country-specific. In Switzerland, moreover, rules still
      differ from one canton to another and a new transplantation law is at present
      under consideration. To avoid further shortage of organs, various models have
      been suggested (such as rewarded giftings) but rejected on ethical grounds. On
      the recipients' side the main discussion centres on who should be the first to
      receive an offered organ. Specific questions on xenotransplansplantation and
      transplantation in newborns are briefly addressed.

PMID- 9782550
TI  - [Political and economic aspects of heart transplantation].
AB  - Organ transplant, like any other area of modern medicine, has manifold
      implications for human values and ethics, while sociology, law, economics and
      politics are equally involved. A brief review is presented of the political and
      economic aspects of cardiac transplantation, covering a short overview of current
      Swiss legislation, the problem of organ allocation, limitation of transplant
      centres, restriction of transplant medicine to public hospitals, cost of
      transplant procedures and subsequent treatment, and costs generated by
      alternative options such as ventricular assist devices. Current transplant
      medicine is affected by a growing shortage of organs, despite the fact that organ
      transplantation is generally well accepted by the public. On the other hand, the
      steadily growing disproportion between the number of organs available and the
      overall number of potential recipients is a source of concern for transplant
      surgeons and the medical profession, as well as the community at large. To be
      able to face these significant problems, transplant centres should offer all
      aspects of treatment for heart failure. In particular, before cardiac transplant
      is offered to a patient, all aspects of more conservative treatment should be
      exhaustively discussed. The economic aspects of each type of transplantation are
      usually discussed, but the cost of a transplant procedure should be compared with
      that of conventional treatment. The increasing use of all currently available
      options (including mechanical and antiarrhythmic bridging) makes a critical
      confrontation with the economic implications necessary. Assumptions based on
      current literature suggest that heart transplant generates additional costs of
      approximately CHF 50,000 per year of extended life. The treatment of heart
      failure involves additional costs of CHF 20,000 per year, provided only a few
      hospitalizations are necessary. CHF 80,000 of the cost of a heart transplant is
      refunded. Medical treatment in the first year after transplant mainly includes
      immunosuppressive drugs, antibiotic and antihypertensive medication, involving
      additional costs of CHF 20,000. The future will require complete use of all
      conventional treatment modalities, recipient selection, strengthened social
      rehabilitation and a quality control database, as well as consensual
      recommendations and coordination in research, follow-up and basic treatment.

PMID- 9782551
TI  - [Therapy refractory pneumonia?].

PMID- 9782552
TI  - [Complementary medicine in health insurance. Economic analysis of the effects of
      including complementary procedures in health insurance. Project within the scope
      of the "Complementary Medicine" Research Program 34].

PMID- 9782553
TI  - Not all coarctations are born equal. Aortic arch hypoplasia and its peculiar
      collateral circles.

PMID- 9782554
TI  - Aortic and mitral valve replacement through a minimally invasive approach.
AB  - Less invasive approaches to cardiovascular surgery are used increasingly to
      reduce surgical trauma and shorten hospital stay. The rarely used upper partial
      sternotomy and parasternal incision can confer the advantages of a smaller
      surgical wound: reduced blood loss, decreased risk of infection, shorter
      intubation, earlier discharge, decreased postoperative pain, and a smaller,
      cosmetically more acceptable postoperative scar. Moreover, reoperation is less
      hazardous, because the pericardium was not completely dissected. From the
      beginning of December 1996 to the end of January 1998, a minimally invasive
      approach was used for aortic valve replacement in 10 patients, and for mitral
      valve replacement in 2 patients. Patients with coronary artery disease, aneurysm
      of the ascending aorta, and poor ejection fraction were excluded from the group,
      but diabetes mellitus, obesity, and impaired pulmonary function were not
      considered contraindications to the operation. No patients required conversion to
      full sternotomy or reoperation. There were no wound infections, neurological
      deficits, or fatalities. The technique has proved safe, effective, and
      aesthetically acceptable to the patient.

PMID- 9782555
TI  - Minimally invasive reoperation through a lateral thoracotomy for circumflex
      coronary artery bypass.
AB  - We report 4 cases of redo coronary artery bypass grafting in which the circumflex
      coronary artery was successfully revascularized using a minimally invasive
      approach. In reoperative cases, it is easier to approach the circumflex coronary
      artery from the left side than from the front. Minimally invasive direct coronary
      artery bypass technology has made it possible to avoid using cardiopulmonary
      bypass. In our 4 cases, the revascularization procedure was performed via a small
      left thoracotomy, and without cardiopulmonary bypass. The patients made a good
      recovery and are free of angina 22 months after operation. We conclude that the
      thoracotomy approach provides the opportunity to avoid several hazards: a redo
      sternotomy, dissection of a hostile mediastinum, and manipulation of the heart.

PMID- 9782556
TI  - Limited-access coronary artery bypass grafting. The Texas Heart Institute
      experience.
AB  - Limited-access coronary artery bypass grafting, without the aid of
      cardiopulmonary bypass, is being performed with increased frequency, but its
      indications are not well defined. To determine the outcome of, and indications
      for, this procedure, we analyzed our experience with limited-access coronary
      artery bypass grafting. Between February 1996 and June 1998, 84 patients
      underwent limited-access coronary artery bypass grafting at our institution. We
      retrospectively divided these patients into 2 groups: a high-risk group with
      complex disease and multiple comorbidities (n = 56), and a low-risk group with
      uncomplicated disease (n = 28). There were 2 perioperative deaths (2%), and both
      of them occurred in high-risk cases. Early and late complications included
      myocardial infarction (2 cases), recurrent angina necessitating revascularization
      (2 cases), and multisystem dysfunction (1 case). Compared with conventional
      bypass grafting, limited-access coronary artery bypass grafting offered a smaller
      skin incision, fewer arrhythmias, less blood loss, less need for inotropic drugs,
      shorter hospitalization, lower cost, and quicker recovery time. Limited-access
      coronary artery bypass grafting might have a role in treating high-risk patients
      who have complex disease and require single-vessel bypass. Anastomosis can be
      challenging, however, if the target coronary artery is small, calcific, or
      intramyocardial. Moreover, the long-term results are unknown. Therefore,
      nonselective use of limited-access coronary artery bypass grafting is
      unjustified.

PMID- 9782557
TI  - Coronary artery bypass for isolated disease of the left anterior descending
      artery. Late survival of 648 patients.
AB  - We studied a series of 648 consecutive patients who underwent coronary artery
      bypass grafting for isolated primary disease of the anterior descending coronary
      artery. We evaluated the patients periodically during a long-term follow-up
      period of up to 17 years. We studied factors such as survival, survival without
      acute event (i.e., acute myocardial infarction, repeat coronary artery bypass,
      and percutaneous transluminal coronary angioplasty), and asymptomatic survival
      (i.e., survival without acute event or angina). We further analyzed these factors
      as they occurred in patients who received only saphenous vein grafts versus their
      occurrence in patients who received internal mammary artery grafts. There was 1
      death in the early postoperative period (defined as 30 days or earlier after the
      operation). The 5-, 10-, and 15-year survival rates were 94.8%, 86.6%, and 72.2%,
      respectively. These survival rates are slightly better than those of an age- and
      sex-matched United States census population. In our series, the rates of
      survival, event-free survival, and asymptomatic survival were better, although
      not significantly so, in the group of 108 patients in whom the internal mammary
      artery was used as the bypass conduit. We conclude that patients who undergo
      coronary artery bypass grafting for isolated disease of the left anterior
      descending coronary artery enjoy normal survival rates, in comparison with the
      survival rates of an age- and sex-matched United States census population,
      through at least the 1st 16 postoperative years. Additionally, patients who
      receive an internal mammary artery bypass graft have slightly better rates of
      survival, event-free survival, and asymptomatic survival than do those who
      receive only saphenous vein grafts.

PMID- 9782558
TI  - Valve replacement under retrograde warm-blood cardioplegia. Results in 287
      patients.
AB  - We studied 287 consecutive patients who underwent valve replacement procedures
      under retrograde warm-blood cardioplegia between 1 March 1992 and 30 June 1997
      (64 months). Some of the procedures were performed in combination with other
      operations (70), but most (217) were isolated. Thirty patients had undergone
      previous "open" procedures and another 25 patients had undergone prior "closed"
      procedures. The 30-day postoperative mortality rate was 3.8% (11 deaths). In 7
      patients, the cause of death was not cardiogenic. We did not observe any instance
      of right ventricular failure, perforation of the coronary sinus, phrenic nerve
      palsy, or wound infection. These results indicate that retrograde warm-blood
      cardioplegia provides excellent myocardial protection of both ventricles during
      valve replacement.

PMID- 9782559
TI  - Myocardial injury caused by an anaphylactic reaction to ampicillin/sulbactam in a
      patient with normal coronary arteries.
AB  - A 63-year-old woman presented with an exacerbation of her chronic obstructive
      pulmonary disease. While receiving an infusion of ampicillin/sulbactam, she
      developed anaphylaxis-induced myocardial injury. Subsequent coronary angiography
      revealed minimal atherosclerosis of her coronary arteries. The patient remained
      under continuous observation and cardiac monitoring throughout her reaction, thus
      providing unique insight into the pathophysiology of myocardial injury caused by
      anaphylaxis. The medical literature that pertains to this phenomenon is
      discussed.

PMID- 9782560
TI  - Amiodarone for control of recurrent ventricular tachycardia secondary to cardiac
      metastasis.
AB  - Metastatic tumors of the ventricles may cause symptomatic ventricular tachycardia
      such as described in this 66-year-old man, who presented with recurrent
      presyncope. The tumor may be readily diagnosed by 2-dimensional echocardiography,
      ultrafast computed tomography, or magnetic resonance imaging. Such tumors usually
      indicate an advanced stage of disease, and curative treatment is rarely possible.
      However, in this patient, effective control of the arrhythmia was achieved with a
      moderate dosage of oral amiodarone (600 mg daily for 4 weeks, then 400 mg daily),
      and he had no further episodes of presyncope. This report shows that the
      effectiveness of amiodarone in the control of symptomatic ventricular
      tachycardias may also extend to those that are probably secondary to metastatic
      tumors of the heart.

PMID- 9782561
TI  - Development of advanced pulmonary vascular disease in D-transposition of the
      great arteries after the neonatal arterial switch operation.
AB  - We report the case of a neonate with D-transposition of the great arteries who,
      after undergoing an uneventful arterial switch operation at the age of 4 days,
      was found at the age of 42 months to have developed advanced pulmonary vascular
      disease. Because the arterial switch operation was performed when our patient was
      only 4 days old, this case challenges the hypothesis that postnatal hemodynamics
      alone dictate the development of advanced pulmonary vascular disease in infants
      and children with transposition of the great arteries.

PMID- 9782562
TI  - Surgical treatment of abdominal aortic aneurysm in association with horseshoe
      kidney. Three case reports and a review of technique.
AB  - Horseshoe kidney is a rare congenital anomaly that can create various technical
      problems during surgery for repair of abdominal aortic aneurysm. The diagnosis of
      this anomaly should be confirmed preoperatively in order to plan surgical
      strategy. Nowadays, in more than 90% of all cases, ultrasonography, contrast
      computerized tomography, urography, and angiography are the best instrumental
      methods of detecting this anomaly in association with abdominal aortic aneurysm.
      The transperitoneal approach assures the best exposure of the kidney, the
      ureters, the aneurysm, and both iliac vessels, but the renal isthmus can pose a
      problem in reimplanting aberrant renal arteries. When it is known preoperatively
      that renal revascularization should be performed, the left extraperitoneal
      approach is a better choice. In any event, the coexistence of horseshoe kidney
      and abdominal aortic aneurysm does not preclude the treatment of the latter. In
      elective surgery of abdominal aortic aneurysm, the morbidity and mortality rates
      in the presence of horseshoe kidney are much the same as those in the presence of
      normal kidneys. The best results in this kind of surgery are obtained by adapting
      one's surgical technique to each anatomical variant that is encountered.

PMID- 9782563
TI  - Coarctation of the aorta with right aortic arch. A rare case and atypical
      clinical picture.
AB  - We report the case of a 13-year-old girl with a diffusely hypoplastic right
      aortic arch, anomalous origin of the left subclavian artery, and a small,
      insignificant ventricular septal defect. The patient's pulse was forceful at the
      carotid arteries, but it was markedly weaker at all extremities. Catheterization
      revealed that both common carotid arteries arose from the dilated ascending
      aorta; the right subclavian and vertebral arteries arose from the hypoplastic
      posterior segment of the aortic arch, and the left subclavian artery arose from
      the normally developed descending aorta. The pressure gradient between the
      ascending and descending aorta was 80 mmHg. A bypass grafting procedure was
      performed to connect the ascending and the upper abdominal aorta. No pressure
      gradient remained after the operation, nor was a gradient detected during 2 years
      of follow-up. The origin of both subclavian arteries distal to the area of
      coarctation resulted in an atypical clinical picture and delayed diagnosis. Ten
      previously reported cases of coarctation of the aorta with right aortic arch are
      reviewed.

PMID- 9782564
TI  - Congenital subclavian steal syndrome in an adult with a left aortic arch.
AB  - To our knowledge, all of the cases of congenital subclavian steal syndrome
      encountered to date in adults have involved a right aortic arch. We present an
      angiographically proven case of congenital subclavian steal syndrome involving a
      left aortic arch in an adult.

PMID- 9782565
TI  - Teaching cardiology auscultation. A wireless FM broadcast system.

PMID- 9782566
TI  - Percutaneous stent-graft for treatment of isolated lliac aneurysm.

PMID- 9782567
TI  - Staphylococcal endocarditis in pregnancy.

PMID- 9782569
TI  - Genesis of the uraemic syndrome: role of uraemic toxins.
AB  - A variety of signs and symptoms constituting the uraemic syndrome may be related
      to the retention and accumulation of uraemic toxins. Several identified (and yet
      unidentified) uraemic toxins of low molecular weight are removed at least in part
      by dialysis therapy resulting in marked improvement of multiple organ
      dysfunctions and clinical symptoms. However, many abnormalities persist due to
      the high protein binding of several uraemic toxins or their high molecular weight
      associated with inadequate dialysis clearance. Moreover, carbamoylation of amino
      acids and proteins in uraemia as well as metabolic acidosis contribute to the
      functional and metabolic abnormalities of the uraemic state. Uraemia interferes
      with the function of polymor-phonuclear leukocytes by deranging their cellular
      biochemistry and biology. P-cresol and several newly identified granulocyte
      inhibitory proteins are responsible for reduced chemotaxis, oxidative activity,
      intracellular killing of bacteria, and glucose consumption by polymorphonuclear
      leukocytes. Hyperhomocysteinaemia is an independent risk factor for vascular
      disease in end-stage renal disease patients. Uraemic toxins interfere with
      calcitriol synthesis and concentration or activity of the calcitriol receptor.
      Advanced glycolysation end-products (AGEs) accumulate as a result of impaired
      renal excretion. AGE peptides may represent a modern-day version of "middle
      molecule" toxicity or uraemia. Of potential clinical importance are pentosidine-,
      imidazolone- and carboxymethyllysine-modifications of beta 2-microglobulin with
      respect to the development of uraemia associated amyloidosis. Several uraemic
      toxins also affect nitric oxide pathway. Particularly, dimethyl-L-arginine (ADMA)
      is a potent inhibitor of nitric oxide synthesis. Parathyroid hormone satisfies
      the strict criteria of an uraemic toxin. Many uraemic symptoms can be attributed
      to the excess of parathyroid hormone in patients with chronic renal failure.
      Finally, recent investigations indicate, that one or more dialyzable uraemic
      toxin(s) suppress(es) appetite and may contribute to malnutrition in uraemia.

PMID- 9782568
TI  - ATSDR evaluation of health effects of chemicals. V. Xylenes: health effects,
      toxicokinetics, human exposure, and environmental fate.
AB  - Xylenes, or dimethylbenzenes, are among the highest-volume chemicals in
      production. Common uses are for gasoline blending, as a solvent or component in a
      wide variety of products from paints to printing ink, and in the production of
      phthalates and polyester. They are often encountered as a mixture of the three
      dimethyl isomers, together with ethylbenzene. As part of its mandate, the Agency
      for Toxic Substances and Disease Registry (ATSDR) prepares toxicological profiles
      on hazardous chemicals found at Comprehensive Environmental Response,
      Compensation, and Liability Act (CERCLA) National Priorities List (NPL) sites
      that are of greatest concern for public health purposes. These profiles
      comprehensively summarize toxicological and environmental information. This
      article constitutes the release of the bulk of this profile (ATSDR, 1995) into
      the mainstream scientific literature. An extensive listing of known human and
      animal health effects, organized by route, duration, and end point, is presented.
      Toxicological information on toxicokinetics, biomarkers, interactions, sensitive
      subpopulations, reducing toxicity after exposure, and relevance to public health
      is also included. Environmental information encompasses physical properties,
      production and use, environmental fate, levels seen in the environment,
      analytical methods, and a listing of regulations. ATSDR, as mandated by CERCLA
      (or Superfund), prepares these profiles to inform and assist the public.

PMID- 9782570
TI  - The search for the uremic toxin: the case for carbamoylation of amino acids and
      proteins.
AB  - Urea and cyanate, spontaneously transformed from urea, are increased with
      decreased renal function becoming potential toxins. Isocyanic acid, the active
      form of cyanate, carbamoylates proteins, amino acids and other molecules,
      changing molecular structure and function in vivo. Carbamoylation can occur at
      multiple sites with a cumulative effect over the the life-span of the molecule.
      Carbamoylation converts free amino acids to carbamoyl-amino acids (C-AA). C-AA
      interfere with protein synthesis and transamination reactions and contribute, in
      part, to protein-malnutrition. Insulin-sensitive glucose uptake is decreased by
      carbamoyl-asparagine. Cyanate inhibits superoxide release from neutrophils to an
      extent that interferes with microbiocidal activity. Antihomocitrulline antibodies
      identified homocitrulline (epsilon-amino-carbamoyl lysine) in situ in proteins in
      neutrophils in end stage renal disease. Also in uremic patients, homocitrulline
      was located in proteins in renal tissue but was not found in normal transplanted
      kidneys. Carbamoylated human low density lipoprotein interferes with human
      receptor binding, has decreased clearance, and is auto-immunogenic in animals.
      Carbamoylated insulin has decreased biological activity and changed immunological
      reactivity. Carbamoylation at a site of molecular activity can affect molecular
      function of enzymes, co-enzymes, antibodies, hormones and receptors. Carbamoyl
      molecules can block, enhance, or be excluded from metabolic pathways, and can
      affect binding and trafficking, thereby influencing the fate of non-carbamoylated
      molecules. Normal renal function removes C-AA. In uremia, C-AA are removed by
      residual renal function or dialysis. Toxicity of cyanate is not an "all or none"
      phenomenon, but the actions of cyanate are a contributing factor in uremia.
      Removal of urea, cyanate and carbamoyl-molecules partially alleviates the
      morbidity and mortality of renal disease.

PMID- 9782571
TI  - Screening for platelet auto-antibodies by flow cytometry and their evaluation by
      the MAIPA technique.
AB  - The determination of platelet antibodies assists in the diagnosis of immune
      thrombocytopenia. Among the various techniques which have been used two major
      ways for the determination of these antibodies have entered the routine use,
      determination of in vivo platelet bound total IgG, termed platelet-associated
      IgG, PAIgG, and that of specifically to particular platelet glycoproteins bound
      IgG, GP-IgG. The former has been found to be non-specific, and the evaluation of
      the latter is rather laborious. Furthermore, both require a large number of
      platelets. By flowcytometry, however, PAIgG can be determined even if platelet
      counts are very low. We therefore evaluated in 30 patients' samples if the
      flowcytometric determination of PAIgG can serve to screen for platelet
      antibodies. Positive samples subsequently are evaluated by a glycoprotein
      specific detection technique (MAIPA). We show that in patients with suspected
      autoimmune thrombocytopenia (AITP) and in secondary AITP PAIgG is elevated in
      83%. However, only 30% of patients' samples have detectable antibodies by the
      MAIPA technique. Based on the findings that by the MAIPA technique antibodies
      were only detectable in samples which had also elevated levels of PAIgG we
      consider the flowcytometric determination of PAIgG useful for screening, prior to
      the more laborious investigation by the MAIPA assay.

PMID- 9782572
TI  - Defecatory disorders in de novo Parkinsonians--colonic transit and electromyogram
      of the external anal sphincter.
AB  - Constipation is very common in Parkinson's disease. It is still not known whether
      constipation is due to a slow transit of the colon or an outlet obstruction. We
      examined 25 patients (11 women, 14 men, mean age 62 years) with newly diagnosed
      idiopathic Parkinson's disease. All patients had typical clinical symptoms (with
      an average score of 11.4 points on the Webster scale); the diagnosis was
      confirmed by 18F-Dopa-PET. In all patients the colon transit time was measured
      with radioopaque markers. Pudendal nerve lesions were excluded by neurography of
      the pudendal nerve. Electromyography of the external anal sphincter was performed
      with concentric needle electrodes in the right and left lateral position. Colon
      transit time in the patients averaged 3.7 days, with pathologically prolonged
      transit (> 4 days) in 6 patients (24%). Four patients (16%) showed mild
      neurogenic changes on sphincter EMG (16%). In three other cases (12%) long
      duration and large amplitude of motor unit action potentials (MUAPs), and a
      reduced interference pattern during maximal voluntary effort indicated a severe
      neurogenic lesion. One patient presented with involuntary contractions of the
      external anal sphincter at rest, which increased during strain (anism).

PMID- 9782573
TI  - [Acquired disorder of thirst perception with intact osmoregulation of
      vasopressin].
AB  - We report a 45 y old male patient with severe hypodipsia, but intact vasopressin
      secretion and maximal renal response to vasopressin. The patient presented during
      hot summer days, 18 months after a frontal lobe hemorrhage due to a ruptured
      aneurysm, with severe hypernatremia (171 mmol/L) and a plasma osmolality of 348
      mosm/kg. He was awake and had no interest in fluid intake. After initial
      correction, a thirst test for 36 hours was performed. Plasma osmolality rose from
      295 to 320, urine osmolality rose from 220 to 700 mosm/kg, while plasma
      vasopressin levels increased more than 3-fold. Throughout the test the patient
      did not exhibit appreciable thirst. The intact osmoregulation of vasopressin as
      evidenced by the plasma levels and the elicited renal response, indicates that a
      selective acquired disturbance of thirst is present. Whether the thirst center is
      destroyed or/and thirst recognition (frontal lobe affection) is disturbed
      primarily, can not be decided.

PMID- 9782574
TI  - Franz Kafka, Sigmund Freud and Markus Hajek. A connection in life and death.
AB  - When Sigmund Freud was taken ill in 1923 with a malignant tumor of his right
      upper jaw he was initially treated by the famous Viennese rhino-laryngologist,
      Professor Markus Hajek. One year later, Franz Kafka, who was suffering from
      pulmonary tuberculosis which had spread to the larynx, was likewise placed under
      the care of this distinguished specialist. Neither of the encounters proved
      beneficial from the professional point of view and both well-known patients
      received remarkably poor attentions in keeping with the general autocratic
      attitude by clinical chiefs of the time in Vienna. Franz Kafka was terminally ill
      when he came to Hajek and no treatment was yet available for the disabling and
      painful laryngeal complication of his advanced tuberculosis. He died about a
      month after leaving Hajek's ward in Vienna. Sigmund Freud required repeated
      subsequent operations on his jaw and the insertion of a prothesis. Hajek had
      handed Freud over to Hans Pichler for further care and it was entirely due to the
      skill of this extremely competent and empathetic maxilliary surgeon that Freud
      lived for another 16 years, working to almost full capacity.

PMID- 9782575
TI  - [Liver transplantation in acute liver failure: who? When? How?].

PMID- 9782576
TI  - [The artificial liver--an interim report].
AB  - A Bioartificial Liver (BAL) is not available to date. Human therapeutic
      applications of different systems of BAL as of 1998 are presented and discussed.
      It is concluded that--as for now--no artificial liver device has gained any
      importance for the treatment of liver failure, and that some critical issues in
      this field of research have not been sufficiently investigated and/or are not
      resolved. This review analyzes reports of clinical applications of BAL from the
      following research groups (numbers in brackets indicate patients treated with an
      artificial liver device): Demetriou/Rozga, Los Angeles (31 patients), Williams,
      London (1 patient); Gerlach, Berlin (1 patient); Strom, Virginia (5 patients).
      The BAL systems used in these studies cannot be directly compared because there
      are considerable differences in the quality and in quantity of the functional
      unit employed in bioreactors, the experimental design, patient selection, to
      mention just a few points. None of the systems investigated so far could
      convincingly prove its effectivity in replacing impaired liver function neither
      in animal models nor in a clinical application. It remains to be shown, whether
      liver cells cultured in bioreactors remain stable, i.e. viable and functionally
      active, for a sufficient period of treatment. Selected metabolic or detoxifying
      functions of the bioreactor are difficult to assess, since these functions do not
      necessarily serve as pars pro toto for the complex clinical presentation of liver
      failure and therefore cannot sufficiently validate any organ replacement system.
      Furthermore, since some applications combine biological units with other
      components, such as active charcoal, it be-comes even more difficult to assess
      the role of hepatocytes in these settings. Case reports of patients treated with
      BAL usually refer to BAL as a "successful bridge to transplant", thereby
      demonstrating the positive effect of orthotopic/auxiliary liver transplants in
      the treatment of acute liver failure rather than the potential benefit derived
      from an artificial liver device. Randomised studies have been proposed and urged
      for years in order to prove the effectivity of these systems which, in part, are
      already available for clinical use. Because of the heterogeneous patient group in
      question the design of such protocols will be a difficult task. It must be asked,
      whether currently used artificial liver systems have left basic science research
      too early; the use of "black box" applications in humans cannot draw its
      legitimation merely from the fact that an effective conservative treatment of
      liver failure is not available so far.

PMID- 9782577
TI  - [Prognostic factors in acute liver failure].
AB  - Acute liver failure is defined as acute severe, potentially reversible hepatic
      failure complicated by cerebral dysfunction. The high mortality rate of between
      50% and 90% justifies early transfer to a specialised centre with the possibility
      of orthotopic liver transplantation to ensure adequate intensive care monitoring
      and treatment, 57 patients with acute liver failure (34 female, 23 male, aged 6
      to 87 years, median 33 years) treated at our intensive care unit during the past
      10 years were analysed retrospectively. Various factors and laboratory data were
      analysed in respect to their prognostic value. Depending on the aetiology, the
      survival rate in acute liver failure under conservative treatment ranges from 79%
      (amanita intoxication) to 10% (cryptogenic genesis). The most important
      predictive parameter is the extent of cerebral dysfunction. The extent of
      cerebral dysfunction is a determining factor of the survival rate under
      conservative treatment; it ranges from 94% (patients with hepatic encephalopathy
      grade I) to 11% (patients with hepatic encephalopathy grade IV). The occurrence
      of complications such as infections, cerebral oedema, respiratory failure or
      renal failure is also associated with an unfavourable outcome. Additionally,
      various laboratory parameters have a predictive ability. The mortality rate of
      our patients with acute liver failure has decreased from 56% to 32% since early
      intensive care monitoring and treatment and the possibility of acute orthotopic
      liver transplantation were established.

PMID- 9782578
TI  - [Liver transplantation in acute liver failure].
AB  - Acute hepatic failure is characterized by jaundice and hepatic encephalopathy
      within eight weeks after the onset of disease. Although acute hepatic failure is
      a rare occurrence, its rapid progression and high mortality (50 to 90%, depending
      on the etiology of disease) necessitate immediate intervention. In the absence of
      causal therapy, orthotopic liver transplantation is currently the only definitive
      and effective means of treating acute hepatic failure in Europe, acute hepatic
      failure accounts for 11% of all liver transplantations. At the University
      department of transplantation surgery in Vienna a total of 27 patients with acute
      hepatic failure underwent 31 liver transplantations in the last 10 years
      (1.1.1987 to 31.12.1996). Twenty (74%) of the 27 patients survived the acute
      event and were discharged from hospital in good general condition after a median
      postoperative stay of 25 days (range 14-81 days). Seven patients (26%) died
      between the first and 34th postoperative day (median 26 days) in the intensive
      care unit, although all potential modern options of intensive care and surgery
      were used. The causes of death were irreversible cerebral edema (n = 3), multiple
      organ failure due to bacterial sepsis (n = 3) and uncontrollable haemolysis (n =
      1). With a 3-year graft survival rate of 70% the 3-year patient survival rate was
      74%. A retrospective analysis of our patients revealed that the postoperative
      graft function and the incidence of re-transplantation were significant
      prognostic factors (p < 0.05) for survival following orthotopic liver
      transplantation for acute hepatic failure. In the absence of further
      prognostically relevant preoperative indices and in consideration of the
      potentially fulminant progression of disease, we strongly recommend that any
      patient, in whom acute hepatic failure is suspected, is immediately transferred
      to a specialized center with experience both in the conservative treatment of
      acute hepatic failure and emergency liver transplantation.

PMID- 9782579
TI  - [Cyclosporin A therapy in steroid-refractory patients with chronic inflammatory
      bowel diseases].
AB  - About eighty percent of patients with severe ulcerative colitis refractory to
      steroids are responsive to intravenous cyclosporine therapy within a few days.
      However, no controlled data are available on intravenous cyclosporine therapy in
      steroid refractory Crohn's disease. In this study 7 patients with severe
      ulcerative colitis and 4 patients with active Crohn's disease unresponsive to
      prednisone were treated with high dose intravenous cyclosporine. A response was
      estimated by a decrease of Crohn's disease activity index (Best) and colitis
      activity index (Rachmilewitz). Six of 7 patients with ulcerative colitis showed a
      significant decrease in colitis activity index (index before therapy: 15 +/- 2;
      one week later: 7 +/- 1; p < 0.001). In these patients prednisone could be
      tapered to a dose less than 20 mg/day within 6 months during oral cyclosporine
      and concomitant azathioprine therapy. Cyclosporine medication was withdrawn
      within a few weeks and the clinical response could be preserved for another 6
      months. In 3 of 4 patients with Crohn's disease intravenous cyclosporine led to a
      temporary improvement of the Crohn's disease activity index (before treatment:
      343 +/- 43, after one week: 194 +/- 20; p < 0.05). Nevertheless, all of these
      patients had an early relapse under oral cyclosporine therapy. Our data confirm
      the efficacy of intravenous cyclosporine as a rapid acting drug for severe
      ulcerative colitis. Maintenance therapy with azathioprine preserved the clinical
      response for one year. In patients with steroid refractory Crohn's disease
      intravenous cyclosporine showed only a short term effect.

PMID- 9782580
TI  - [Every day competence].

PMID- 9782581
TI  - [Every day competence: a construct in search for an identity].
AB  - The goal of this paper is to contribute to conceptual issues associated with the
      construct of everyday competence. After the description of reasons for the
      increased attention which everyday competence has found within gerontology, the
      first section of this work serves to shed light on six research traditions with
      relevance for everyday competence: (1) Research on everyday cognitive processes,
      (2) ADL/IADL research, (3) leisure time research, (4) coping research, (5) time
      budget research, and (6) ecological gerontology research. In the second section,
      two influential models of everyday competence, namely those of Margret Baltes and
      Sherry Willis, are discussed. Finally, an integrative conception of everyday
      competence, which is aimed to combine aspects of the six research traditions with
      elements of the two models of everyday competence, is suggested.

PMID- 9782582
TI  - [Every day life experiences of healthy and mobility impaired elderly patients].
AB  - Studies on the everyday life of the elderly often deal with visible behavior. In
      this study, the subjective experience of the everyday living environment was
      investigated, paying special consideration to the role of mobility impairment.
      Two approaches, one oriented toward the subject's experience of the home
      environment, another oriented toward the environmental specifics of the
      individual's favorite place, were employed. Is the experience of living at home
      different for individuals with various levels of competence? Which aspects are
      perceived to be the most important? 84 men and women aged 62-92 years (M = 77
      years) participated in the study. 42 persons were generally healthy; the other 42
      subjects suffered from severe mobility impairment. The experience of the everyday
      environment was assessed in semistructured interviews at home. A content analysis
      of the data gathered using the person-oriented approach resulted in five
      experiential categories. Differences between healthy and mobility impaired adults
      were found in the experience of cognitive, biographical, and spatial dimensions
      of the living environment. Similarities were found in the experience of
      emotional, social, and behavioral dimensions of one's home. Competence loss
      played an important role in how the subjects experienced living at home, yet even
      the mobility impaired experienced their home as an environment which could be
      shaped. The environment-oriented approach showed that the favorite place of
      mobility impaired persons was characterized by higher spatial density. Finally,
      an examination of four home environment profiles using cluster analysis
      illustrated the connection between both person- and environment-oriented
      approaches and offered insights into a transactional perspective of person and
      environment. Even though the subjective experience of one's home environment is
      not easily quantifiable in terms of maintaining everyday competence, it
      nonetheless imparts meaning to the elderly person's daily life.

PMID- 9782583
TI  - [Every day activities and daily mood of the elderly].
AB  - Using the diary method, the correlation between daily mood and everyday
      activities is analyzed. Positive and negative affect were used as indicator of
      daily mood. Duration of social activities and resting during the day were used as
      indicator of daily activities. A total of 55 elderly persons kept a activity and
      mood diary for at least 50 days. The data were analyzed interindividually (using
      regression analyses) and intraindividually (using time series analyses). While
      positive affect and duration of social activities correlate positively in both
      inter- and intraindividual perspective, there is a relationship between negative
      affect and duration of rest only in interindividual perspective. Theoretical and
      practical implications of the results are discussed.

PMID- 9782584
TI  - [Dementias and daily competence: effects beyond ADL and IADL].
AB  - Using a time-budget method in a 3 year longitudinal study with a control group
      design, substantial reductions in the engagement of nonobligatory instrumental,
      social, and leisure activities could be found in a group of mildly to moderately
      demented patients. Controlling these changes for differences in baseline
      parameters, the dementia-specific reduction was about 1 1/2 hours compared to a
      non-psychiatric control group. These clinically relevant changes in activity
      levels underscore the importance of these activity domains with regard to the
      development of diagnostically useful indicators at the early stages of dementia.
      Time-budget methods seem to be particularly useful to close the diagnostic gap
      with regard to the assessment of everyday competence indicators especially at
      early stages of the dementia illness.

PMID- 9782585
TI  - [Identification of acute geriatric patients in the city of Hamburg ("direct data
      collection")].
AB  - In the past the calculation for an in-patient special offer (quantity of beds
      needed) was mainly carried out by diagnosis-based statistics of hospital cases.
      The decision for an in-patient care within a geriatric unit is however influenced
      by factors as "status of self-help abilities", "social situation" and "co
      morbidity". Those factors are investigated either directly by the help of the
      patient himself or by questioning the nurses and/or the medical staff. A new way
      of measuring will be introduced for this questioning. The crucial element is the
      Barthel-Index (BI). Supporting measures are done by the inclusion of main data
      concerning the social situation as well as recording the modified screening
      according Lachs. From the 6th of September until 14th of December 1997 the three
      part measuring technique was used at seven hospitals in Hamburg (amongst them one
      University hospital and one hospital with a geriatric unit) within the framework
      of a representative sample survey. These collected data register 18 admission
      days of all patients of sixty or over who at the time of questioning stayed for
      five days in one of those acute hospitals. In some hospitals some additional data
      were collected at the third or 6th day after admission. Altogether a whole
      "virtual day-admission" of the 60 years old or older patients was collected for
      the City of Hamburg at the 5th day after admission. Out of 425 patients 137 were
      moved or exmitted before questioning, 4 had already died. Out of the rest of 284
      patients two of them refused the questioning, whilst the data of 6 patients were
      not feasible for evaluating. Finally 276 patients were questioned. Out of them
      231 patients are "not potential candidates for a geriatric hospital or a
      geriatric day-care unit", 8 are "candidates for a geriatric day-care unit
      directly after discharge of primary care" and 37 are "candidates for an in
      patient geriatric hospital". The presented three-part question-sheet shows a
      sensitivity of 89.2% and a specification of 92.2%. This measuring technique in
      the hands of a trained examiner appears to be a valid and manageable tool in the
      framework of geriatric consultation as well as for the investigation of own
      directly ascertained statistic datas for "potential candidates for an in-patient
      geriatric hospital".

PMID- 9782586
TI  - [Research and education in geriatrics at German universities and colleges].
AB  - To assess the situation of geriatric research and education at German
      universities, a questionnaire was sent out to all medical faculties (n = 37). The
      response rate was 91.9% (n = 34). There are five universities with a geriatric
      chair (14.7%), one with a department of geriatric medicine within internal
      medicine, and two departments of geriatric psychiatry. At 15 universities
      geriatric research is established (44.1%), but only 12 universities report that
      geriatric contents are implemented in the teaching of medical students. The
      comparison of universities with and without geriatric chairs and departments
      showed big differences. Whereas all universities with geriatric chairs or
      departments conduct geriatric research and offer education in geriatric medicine,
      the others failed to do so. Only 26.9% (n = 7) have geriatric research and 15.4%
      (n = 4) offer medical teaching in geriatrics. There is a strong link between
      geriatric chairs, research, and pregraduate teaching. Geriatric medicine is
      established only at few universities. To improve the overall situation of
      geriatrics in Germany the implementation of further geriatric chairs and
      departments at universities seems to be necessary.

PMID- 9782587
TI  - [Psychometric diagnosis of dementia in clinical gerontopsychiatry practice].
AB  - An extensive battery of cognitive tests is conducted to detect dementia in
      geriatric patients. Based on the ICD-10 diagnostic criteria for dementia the
      diagnosis includes cognitive deficits such as memory impairment and other
      cognitive disturbances in various stages. To establish a profile of cognitive
      deficits and to detect early stages of dementia a combination of psychometric
      tests has proven to be effective and valid (MMSE, SKT, SIDAM, GDS/BCRS, clock
      drawing). To evaluate interrelations between these tests, correlations of total
      scores among 40 randomly chosen geriatric patients were calculated for all tests
      using the Spearman rank-order correlation. The cognitive test battery appears to
      be a reliable instrument for diagnosing people with dementia. Due to advantages
      and shortcomings of each test in evaluating various stages of dementia
      adequately, a combination of tests should be used.

PMID- 9782588
TI  - [Prescription drugs, dizziness and accidental falls in hospital patients over 75
      years of age].
AB  - The review of medication has been recommended as an important part in preventing
      falls. In a random sample of 276 hospital in-patients aged 75 and over, the
      frequency of prescribed drugs which may increase the risk of falling by causing
      dizziness was assessed. Questions about dizziness and previous falls were
      included in a standardized questionnaire. Patients with dizziness reported falls
      10 times more often than patients without dizziness. Prescribed medications
      possibly causing dizziness were very common. Neuroleptics, antidepressants,
      hypnotics/sedatives, and combinations of drugs with hypotensive efficacy were
      significantly more often prescribed in patients who reported dizziness.
      Systematical review of medications appears to be worthwhile, particularly in
      cases with multiple drug prescriptions.

PMID- 9782589
TI  - [Assisted suicide between release and life-long imprisonment].

PMID- 9782590
TI  - [Intravascular ultrasound--the new gold standard?].
AB  - Intravascular ultrasound (IVUS) has evolved to a research tool to an intrinsic
      part of modern invasive cardiology. The main reason is the capability to obtain
      "in-vivo" micro anatomy by means of miniaturized echo-transducers with an outer
      diameter of 2.9-3.5 French. For the first time it is possible to base decisions
      not only on lumenograms but also on vessel wall assessment. The capabilities of
      IVUS can be divided in its diagnostic and intervention associated potentials. The
      diagnostic strength of IVUS is the ability to monitor compensatory coronary
      artery enlargement as a response to arteriosclerosis, to assess intermediate
      lesions, to reveal occult left main stem disease, and angiographically "silent"
      arteriosclerosis. In conjunction with the estimation of intracoronary flow
      reserve, patients with the diagnosis of coronary "syndrome X" can be better
      classified into those with or without early signs of arteriosclerosis.
      Additionally, IVUS is at present the only method allowing the classification of
      coronary artery lesions according to the AHA/ACC Stary classification. The
      intervention associated potentials of IVUS are the ability to allow optimal
      device selection, i.e. rotablators in calcified lesions or atherectomy devices in
      large plaque burden. The effects of PTCA on vessel wall morphology can be studied
      in great detail and the effect on luminal gain can be assessed almost on-line.
      The correlation between IVUS and angiography for estimation of luminal dimensions
      is inferior, because angiography is not able to describe complex luminal
      geometries. Several groups showed that the residual plaque area even after
      angiographically successful PTCA lies still in the range of 60%. A significant
      reduction of this number may influence long-term outcome after PTCA. Minimal
      luminal areas and residual plaque area after PTCA seem to be an indicator of
      restenosis, while the presence or absence of dissections seem to be less
      predictive. Additionally, the main mechanism of restenosis after PTCA is vessel
      shrinkage, not intimal hyperplasia. Intravascular monitoring of stent expansion
      led to high-pressure stent deployment with significant increase in post
      procedural luminal diameters and finally the ability to withhold anticoagulation
      in patients with optimal stent deployment and to lower subacute stent thrombosis
      rates. First results for IVUS guided PTCA show a superior gain in post procedural
      free lumen without an increased complication rate. In the future, integrated
      devices, like balloons on IVUS catheters, steerable catheters, integrated flow
      and pressure transducers, tissue characterisation, and 0.018 inch IVUS guidewires
      will further enhance the usefulness of IVUS.

PMID- 9782591
TI  - [Monckeberg media calcinosis].
AB  - Monckeberg's disease (MD) is characterized by media calcinosis (MC) of the
      arteries of the lower extremities. MC is distinct from atherosclerosis, occurs in
      different vascular beds, and its etiology is unknown. Here, we report a case of a
      46-year old male with no prior medical history of cardiovascular disease, no
      metabolic risk factors, and normal laboratory findings, who presented with
      accidental findings of marked diffuse calcifications along the entire course of
      the femoral superficial and profunda arteries on plain x-ray films. Follow-up
      cardiovascular diagnostics using high resolution B-mode ultrasonography,
      ultrafast CT, and x-ray angiography revealed extensive abluminal arterial wall
      calcification without evidence for premature or advanced intima-related
      atherosclerosis in the abdominal aorta, in the arteries of the pelvis, and the
      lower extremities. Calcifications were also present in the proximal segments of
      the circumflex and left anterior descending coronary arteries. The carotid
      arteries showed no calcium deposits. This observation confirms that MC may occur
      in the absence of secondary risk factors (primary MC) and independently of
      atherosclerosis. Simultaneous involvement of several vascular territories
      including the coronary arteries appears possible. The systemic character of
      primary MC is consistent with a genetical cause of this as yet poorly defined
      disease.

PMID- 9782592
TI  - [Minimally invasive heart surgery--a fad or a clinically recognized therapy
      method?].
AB  - Within the last 5 years new less invasive surgical techniques have been developed
      in the field of cardiac surgery. This new field named "minimally invasive cardiac
      surgery" can be subdivided into techniques which do not require cardiopulmonary
      bypass and are used mainly for coronary artery surgery (called minimally invasive
      direct coronary artery surgery, MIDCAB technique). This MIDCAB procedure can be
      done through a small left anterior thoracotomy or a sternotomy. In addition there
      are other methods which allow the performance of complex cardiac surgery through
      small accesses in combination with the use of an endovascular CPB system and
      internal aortic clamping to achieve cardioplegic arrest (so-called Port-Access
      method). Also for valvular surgery, new surgical techniques were developed
      allowing access to mitral and aortic valves through limited incisions. In
      addition, new less invasive techniques were developed for congenital heart
      surgery. This article will describe the various surgical techniques and define
      the indications for minimally invasive cardiac surgery.

PMID- 9782593
TI  - [Aortic valve replacement as an independent predictive factor for later
      development of aortic dissection].
AB  - Dissection of the ascending aorta (type A) following later after aortic valve
      replacement has been described with increasing frequency. This study analyzes the
      role of aortic valve replacement for the evolution of late dissection. In a
      series of 80 consecutive patients with type A dissection, a previous aortic valve
      replacement had been performed in 12 cases (15%). In addition to arterial
      hypertension (p < 0.001) and Marfan syndrome (p < 0.01), multivariate analysis
      identified previous aortic valve replacement (p < 0.01) as an independent
      predisposing factor for type A dissection. Dissection occurred 3 +/- 4 years
      after aortic valve replacement with a clinical and anatomical profile similar to
      classic dissection as proven by comparison to a group of 62 patients with classic
      dissection associated with arterial hypertension or Marfan syndrome. With 75% and
      66%, respectively, 30 day and 1 year survival of patients with dissection
      following later after aortic valve replacement was similar to patients with
      classic type A dissection. Extensive thinning and/or fragility (p < 0.05) of the
      aortic wall in the presence of a mildly dilated aorta (45 +/- 5 mm) at the time
      of aortic valve replacement was associated with a high risk for late dissection;
      this finding was substantiated by comparison to a control group of 10 consecutive
      patients with a similarly dilated aortic root but no dissection. Type and
      diameter of valve prostheses, cross-clamp time, NYHA functional class, and left
      ventricular ejection fraction were unrelated to late dissection. Previous aortic
      valve replacement is an independent predisposing factor for a dissection of the
      ascending aorta later. At the time of aortic valve replacement, prophylactic
      replacement or wrapping of the ascending aorta should be considered in patients
      with a thinned/fragile aortic wall even without a markedly dilated aortic root.

PMID- 9782594
TI  - [Quantification of cell proliferation with the proliferation marker MIB-1 in
      endomyocardial biopsies after heart transplantation. An aid in diagnosis of graft
      rejection needing treatment?].
AB  - The histological grading of endomyocardial biopsies still represents the gold
      standard in the diagnosis of cardiac allograft rejections. Severe acute
      rejections (grade 3A/3B, ISHLT) after heart transplantation require immediate
      high-dose immunosuppressive therapy. The histomorphological differentiation to
      the rejection requiring no therapy (grade 2) is often difficult. The aim of this
      study is the improvement of the diagnostic identification of therapy-requiring
      rejections using quantification of cell proliferation in the inflammatory
      infiltrate of biopsies. 322 consecutive endomyocardial biopsies from 48 heart
      allograft recipients were immunohistochemically investigated using the monoclonal
      antibody MIB-1 binding selectively to the proliferation associated antigen Ki 67.
      Fifty percent of all biopsies showed cell proliferation: 47.0% in absent or mild
      rejection (0, 1A, 1B) compared to 88.0% in moderate to severe rejection (2,
      3A/3B) (p < 0.01). Proliferating cells were arranged in a focal or perivascular
      pattern in 66.0% and diffuse in 34.0%. The quantity of proliferating cells per
      biopsy--but not the pattern--correlated with the grade of rejection: 0.7% in
      grade 0, 1.4%/5% in 1A/1B, 8.5% in grade 2 up to 18.7% in 3A/3B, and 2.7% in R1
      (p < 0.01, ccorr = 0.65). The amount of proliferating mononuclear cells in the
      inflammatory infiltrate in acute cardiac allograft rejection is proportional to
      the severity of the rejection and thus an aid in the difficult histological
      differentiation of grade 3A/3B.

PMID- 9782595
TI  - [Imaging and differentiation of atherosclerotic plaque with magnetic resonance
      tomography].
AB  - Magnetic resonance (MR) imaging studies have allowed the imaging of an atheroma,
      its size, shape, and lipid contents. The aim of our study was to characterize
      atherosclerotic lesions using a 0.5 T magnet, to delineate plaque components, and
      to compare MR results with histology. Thirty necropsy specimens of human iliac
      arteries were studied. Magnetic resonance imaging studies were carried out on a
      0.5 Tesla superconducting magnet using a 5 cm surface coil. The position for the
      coronal MR planes was oriented by an external marker. The matrix size was 256 x
      256, 4 NEX, and the FOV was 45 mm. The pulse sequences used included SE 520/29
      and SE 2200/28 and 90. Signal intensity (SI) of fibrous plaques increased
      significantly from 28.3 +/- 3.8 to 49.1 +/- 8.2 (p < or = 0.0001) and decreased
      at SE 2200/90 to 24.1 +/- 6.8 (p < or = 0.0001). However, lipid plaque components
      showed no significant change in SI between T1-weighted pulse-sequences (28.2 +/-
      5.4) and T2-weighted pulse-sequences (25.5 +/- 5.9). Only at SE 2200/90 SI of
      lipid plaques decreased significantly (11.8 +/- 3.9, p < or = 0.0001). As
      compared to histology, MR has shown a high sensitivity and specificity in the
      detection of fibrous and lipid plaque components. In conclusions, our study
      demonstrated that MR is highly effective in the characterization of
      atherosclerotic lesions.

PMID- 9782596
TI  - [Dysfunctions of transvenous cardioverter/defibrillator electrode systems:
      clinical significance of system integrated diagnosis and measurement function-
      possibilities of partially automated system control].
AB  - The aim of this study is the analysis of electrical failures in transvenous
      cardioverter/defibrillator (ICD) lead systems with regard to the importance of
      device implemented diagnostic and measurement functions and the potential role of
      an automated device-control in the detection of lead failures. METHODS: All
      consecutive ICD patients at our institution were enrolled in this retrospective
      investigation. The routine follow-up controls consisted in a complete evaluation
      of all diagnostic and measurement ICD features and additional controls in case of
      spontaneous arrhythmia episodes. RESULTS: Two hundred thirty patients, 193 male
      and 37 female, were enrolled in this study (mean age: 61.5 +/- 10.2 years; mean
      LVEF 32 +/- 9%). During a mean follow-up period of 29.5 +/- 18.4 (6-76) months,
      lead failure occurred in 19 patients (8%), 16 patients were implanted with an
      ICD, capable of diagnostic and measurement functions. All nonadequate device
      discharges could be classified as sensing-failure by stored electrograms. Device
      implemented measurement features revealed clinical important information in 13/16
      patients (81%). In 14/16 patients, the lead defect could not be detected during
      routine follow-up. At the time of documented lead failure the safety of the
      implanted devices was already lost in 6/16 patients (38%). CONCLUSIONS: Device
      implemented diagnostic and measurement options are of great importance in the
      early detection of ICD lead failures. The implementation of automated
      measurements of lead related parameters in connection with a patient alert
      function may contribute to a further increase in the safety of ICD therapy.

PMID- 9782598
TI  - [Comment on the contribution: A. Hagendorff et al., Loffler fibroplastic
      endocarditis in the thrombotic stage in isolated right ventricular tissue
      eosinophilia].

PMID- 9782597
TI  - [Anti-bradycardia ventricle stimulation during the vulnerable phase of the heart
      cycle in ICD system with DDD cardiac pacemaker function].
AB  - We report a case of a 56-year-old white female with an ICD system (Ventak AV,
      CPI) implanted because of repeated episodes of ventricular fibrillation and
      preexisting intermittent total AV-block. Several times asynchronic stimulation
      could be observed in the case of ventricular extrasystole stimulating the
      ventricle during different times of depolarization. The reason for undersensing
      of the premature ventricular complexes was a blanking period of 66 ms after
      atrial stimulation. Therefore, the ICD was not able to sense the ventricular
      extrasytole and the stimulation of the ventricle occurred during the vulnerable
      period of the heart cycle. Induction of severe ventricular arrhythmia was not
      documented. Because of missing programmability of the ventricular blanking
      period, no possibility of a safety stimulation, and already maximal sensitivity
      of the ICD, the incidence of these events could only be reduced by increasing the
      lower rate limit of the pacemaker and suppression of the premature ventricular
      complexes by medication.

PMID- 9782599
TI  - [Guidelines for therapy of chronic heart failure. German Society of Cardiology
      Heart and Cardiovascular Research].

PMID- 9782600
TI  - [Vitamin E in rheumatic disease therapy?].

PMID- 9782601
TI  - [Vitamin E in therapy of rheumatic diseases].
AB  - Over the past years, antioxidants, and particularly vitamin E, have received
      considerable attention in the treatment of human diseases. In rheumatology,
      interest has been given to the treatment and prevention of rheumatoid arthritis
      and osteoarthritis. However, the concept of using antioxidant nutrients as
      potential remedies is not new. As early as the sixties, first case reports have
      described beneficial effects of vitamin E in the therapy of osteoarthritis.
      Nonetheless, most of the following studies were not conducted properly, thus, not
      allowing valid inferences about the efficacy of vitamin E. Newer studies with
      sound methodology have shown a beneficial effect in rheumatic diseases, mainly in
      the reduction of pain. This paper reviews current and past studies about vitamin
      E in the treatment of rheumatic diseases.

PMID- 9782602
TI  - [Effectiveness of vitamin E in comparison with diclofenac sodium in treatment of
      patients with chronic polyarthritis].
AB  - In a randomized, double blind parallel group comparison the antiphlogistic and
      analgetic efficacy of high-dosed vitamin E (3 x 400 mg RRR-alpha
      Tocopherolacetat/d) versus diclofenac-sodium has been investigated in
      hospitalized patients with established chronic rheumatoid arthritis. After 3
      weeks of treatment the vitamin E group (n = 42) as well as the diclofenac group
      (n = 43) showed a significant improvement of all assessed clinical parameters.
      Duration of morning stiffness could be reduced under vitamin E treatment from 90
      min to 68 min and under diclofenac treatment from 68 min to 30 min. The joint
      index according to Richie declined from 56 to 46 (vitamin E) and 49 to 34
      (diclofenac). Grip strength increased in the vitamin E group as well as in the
      diclofenac group. In addition, the degree of pain, assessed by a 10 cm visual
      analogue scale, reduced significantly under vitamin E as well as under
      diclofenac. Regarding the therapeutical result both, physicians and patients,
      considered both drugs to be similarly effective. Especially regarding the risk
      profile of NSAR in long-term treatment of chronic rheumatoid arthritis intake of
      high-dosed vitamin E is a possible alternative in the treatment of inflammatory
      rheumatoid diseases.

PMID- 9782603
TI  - [Surgical treatment of aseptic bone necroses of both knee joints in
      antiphospholipid antibody syndrome (APL) by synovectomy, arthrolysis and
      arthroplasty].
AB  - A 22 year old male patient with antiphospholipid-antibody syndrome (APL)
      developed severe bilateral avascular necrosis of both femoral condyles. Extensive
      synovectomy and arthrolysis in combination with an arthroplastic remodeling of
      both knee joints resulted in reduction of pain and joint effusion. Therefore,
      synovectomy and arthroplastic remodeling might be a promising therapy to extend
      the period of time to prosthetic joint replacement in young patients with APL.

PMID- 9782604
TI  - [Severe toe gangrene as an early manifestation of Wegener granulomatosis in a
      young patient].
AB  - Gangrene of digits is a very rare manifestation of Wegener's granulomatosis (WG).
      We report a case of a 29-year-old woman with nonspecific symptoms like fever,
      weight loss, arthralgia, arthritis and high systemic inflammatory signs. On the
      grounds of a presumed infection the patient was treated with antibiotics which
      showed no effect. Within short she complained of pain and paresthesia of the
      right foot with a rapid lividity. Angiography demonstrated multiples stenoses and
      multisegmental occlusions of the lower leg arteries. Together with renal and
      pulmonal symptoms a WG was suspected, the diagnosis being confirmed by kidney
      biopsy and positive cANCAs. A few months after starting a combined therapy with
      cyclophosphamide and corticosteroids the patient showed a partial remission with
      a residual toe gangrene. Comparing the five worldwide reported cases with digital
      gangrene and our presentation there is a concordance of all in the occurrence of
      an extremely high disease activity together with a glomerulonephritis. The
      findings of p-ANCAs in our patient and positive Hbs antigen in another case of WG
      with digital gangrene suggests a relation to panarteriitis nodosa, where gangren
      is more common.

PMID- 9782617
TI  - [Report on the OMERACT IV CONFERENCE 16-20 April 1998 in Cancun/Mexico].

PMID- 9782618
TI  - The past, the present and the future of medicine.

PMID- 9782619
TI  - Penile replantation--a case report.
AB  - The authors submit a successful case of penile replantation. They discuss the
      course of the procedure and document the immediate and long-term result of this
      procedure.

PMID- 9782620
TI  - A further application of buried chip skin grafting.
AB  - Buried chip skin grafting used to close a granulation wound, that cannot be kept
      at rest, or else is in some way irritated, is described. This requires an
      extremely small amount of skin. Although it takes a month to heal, irritation or
      contamination of the grafted area does not affect or have any influence on the
      take of graft survival. Therefore, the patient need not be kept at rest after
      surgery, and can continue with daily living or rehabilitation exercises.

PMID- 9782622
TI  - The use of growth hormone in the treatment of extensive burns: a case report.
AB  - Growth hormone is an anabolic hormone that causes increased cell growth, positive
      nitrogen and calcium balance, lipolysis, hyperglycemia, and promotes protein
      synthesis. Its beneficial effect in burn treatment was proven particularly in
      children, by Herndon's group. The authors report The case of a 12-year-old boy
      with an electrical arc burn of 81% of the BSA, 60% of the BSA being full
      thickness loss. Recombinant human growth hormone (Norditropin, Novo Nordisk) was
      administered at daily doses of 0.52 i.u./kg starting on day 19 post-burn for 15
      consecutive days. The treatment was well tolerated except for mild
      insulinoresistance, which could be easily corrected by slightly increasing the
      insulin added to glucose solutions. After 56 days of intensive care treatment and
      several excision and grafting procedures, the majority of burns were healed.

PMID- 9782621
TI  - Our experience with the use of cerium sulphadiazine in the treatment of extensive
      burns.
AB  - The development of the burn disease with infection as the most important
      complication represents still a major problem in burn patients. With the
      introduction of the method of early surgical excision of the Af1p4r with
      immediate grafting in major burns, improved survival has been achieved,
      particularly in children. However, especially in adults, early massive excisions
      did not prove to be of much benefit for survival. In these cases, more-or-less
      sequential staged excisional procedures have been introduced by many renown burn
      surgeons. In 1976 Monafo et al. presented the cerium nitrate-silver sulphadiazine
      cream (CSD) combination for topical therapy. The addition of 2.2% of the rare
      earth metal cerium salt to silversulphadiazine causes the formation of a
      relatively hard, yellow, leather-like eschar with excellent resistance to
      infection and good long-term adherence to the burn wound. This allows the surgeon
      to perform late tangential excision and immediate autografting thus decreasing
      the open wound size and the rate of severe infections originating in the burn
      wound itself. We report our experience with the treatment of 20 patients with
      deep burns exceeding 20% of the BSA with cerium nitrate-silver sulphadiazine
      cream compared with a similar group of burn patients treated by silver
      sulphadiazine cream alone. CSD proved to be safe and effective in the treatment
      of deep and extensive burns. Its advantages include easy and painless application
      and removal, turning the necrotic skin to yellow, and a leathery crust with good
      resistance to infection, thus enabling later, or staged, sequential excisions in
      cases where early massive excisions are not possible.

PMID- 9782623
TI  - Mortality in pediatric burns in the Prague Burns Centre (1994-1997).
AB  - The authors evaluate the mortality of severely burned children hospitalized in
      the Intensive Care Unit, Prague Burns Centre from 1994 till 1997. There were
      hospitalized 345 children (aged 3 months-15 years, 1%-88% TBSA, mixed superficial
      and deep burns). No child died from burn shock during the early postburn period.
      Five children who died suffered deep burns greater than 50% of TBSA and at
      necropsy there were identified signs of multiple organ system failure which was
      related to infection.

PMID- 9782624
TI  - Our healthier nation: a contrary opinion.

PMID- 9782625
TI  - Taking control of infectious intestinal disease.

PMID- 9782626
TI  - Legionellosis associated with ships: 1977 to 1997.
AB  - Over one hundred cases of legionnaires' disease have been linked to ships, and
      ten cases are known to have died. Most of the cases were associated with cruise
      ships, but a variety of other vessels were also linked to cases. Few vessels were
      investigated microbiologically, and the cases associated with ferries were
      exposed to other sources of infection. Cases appear to be less common among crew
      members than among passengers. To prevent further cases, ship owners, operators,
      and captains need to be diligent in maintaining the water and air conditioning
      systems of their vessels. Whirlpool spas need particular care. Ship-associated
      cases of non-pneumonic legionellosis appear to be rare.

PMID- 9782627
TI  - Human enteric pathogens identified in a London teaching hospital and a rural
      public health laboratory: 1994.
AB  - Two microbiology laboratories, one serving an inner city hospital and one a rural
      public health laboratory, collected data on the outcome of examining faecal
      specimens in 1994. Overall, 6.7% of the investigations were positive, but the
      rates were lower for hospital inpatients, for recently described pathogens, and
      in the absence of relevant clinical details; rates were higher for patients with
      a history of foreign travel. No benefit was gained by examining more than two
      specimens from any patient. Clostridium difficile was the only investigation
      frequently positive among patients already in hospital, and virological tests
      were often positive in patients investigated by general practitioners.

PMID- 9782628
TI  - Salmonella in raw shell eggs in Northern Ireland: 1996-7.
AB  - The shells and contents of 2090 packs of six raw eggs from shops in Northern
      Ireland were examined for the presence of salmonella between April 1996 and
      October 1997. Nine isolates of salmonella were detected from separate packs of
      eggs (0.43%). One of the isolates was from egg contents (0.05%), where salmonella
      can proliferate to levels likely to cause human infection if the egg is
      inadequately cooked. Visible dirt and organic contamination were poor predictors
      of salmonella contamination since most contaminated eggs had apparently clean and
      uncracked shells. Contaminated eggs were more likely to have been sold from small
      shops than supermarkets. Sampling for uncommon pathogens is expensive, labour
      intensive, and yields many negative results. The small numbers of positive
      results make it particularly susceptible to variations between methods. It
      continues to be important to cook eggs thoroughly to eliminate the risk of
      salmonellosis since this survey suggests that over 10,000 boxes containing one or
      more contaminated eggs may be sold in Northern Ireland each year. Caterers should
      use pasteurised liquid egg. A system of branding to enable eggs to be traced to
      individual flocks would assist in the investigation of outbreaks.

PMID- 9782629
TI  - Is food poisoning a clinical or a laboratory diagnosis? A survey of local
      authority practices in the south Thames region.
AB  - An audit of South Thames infectious disease surveillance systems in 1995 revealed
      large inconsistencies between the numbers of food poisoning records held on local
      databases and the numbers of food poisoning notifications reported to the Office
      for National Statistics (ONS), then called the Office of Population Censuses and
      Surveys. In March 1996 a questionnaire sent to each local authority in South
      Thames asked what action was usually taken when a laboratory report of
      cryptosporidium, campylobacter, salmonella, or giardia was received unsupported
      by a notification of food poisoning. All 51 local authorities responded to the
      questionnaire. Forty-eight reported salmonella to ONS, 38 reported
      cryptosporidium, 38 campylobacter, and 37 giardia. Some local authorities
      considered whether a food or water source was evident or suspected before
      reporting. Patterns of notification varied between geographical areas.
      Differences between local authorities' interpretations of the requirement to
      report to ONS the isolations of food poisoning organisms from patients make it
      difficult to analyse food poisoning statistics. We would recommend the adoption
      of a simple approach, in which laboratory reports and notifications are
      reconciled locally. A case should be reported to ONS only if the doctor who
      notified or arranged for an examination of stool suspected food or waterborne
      transmission initially.

PMID- 9782630
TI  - General outbreaks of infectious intestinal disease in England and Wales: 1995 and
      1996.
AB  - One thousand nine hundred and nineteen general outbreaks of infectious intestinal
      disease in England and Wales were reported to the PHLS Communicable Disease
      Surveillance Centre (CDSC) between 1 January 1995 and 31 December 1996, compared
      with 1073 in the previous two years. A minimum data set was received for 1568
      (82%) of the 1919 outbreaks. Over 40,000 people were affected and about 2% of
      those who were ill were admitted to hospital. Seventy-one deaths were reported.
      The duration of outbreaks varied between less than one day and 202 days (median
      six days) according to the pathogen. Small round structured virus (SRSV) (43%)
      and salmonellas (15%) were the most commonly reported pathogens. In almost a
      quarter of the outbreaks (24%) the aetiology was unknown. Over half the outbreaks
      (64%) were reported to be transmitted from person to person, most of which were
      due to SRSV and occurred in residential homes and hospitals. Twenty-two per cent
      of outbreaks were described as mainly foodborne, 51% of which were due to
      salmonellas. The number of outbreaks reported in each region ranged from 52 in
      Wales to 512 in Northern and Yorkshire.

PMID- 9782631
TI  - An outbreak of Salmonella enteritidis phage type 5a infection in a residential
      home for elderly people.
AB  - The first outbreak of Salmonella enteritidis phage type (PT) 5a infection to be
      reported occurred after a party in a residential home for elderly people in May
      1995. The party was attended attended by 96 residents, staff and guests. S.
      enteritidis PT5a was isolated from 14 of the 25 clinical cases identified after
      the party and S. enteritidis PT4 from another clinical case. Two elderly
      residents with S. enteritidis PT5a infection died. Infection with S. enteritidis
      PT5a was associated with consumption of prawn in mayonnaise vol-au-vents, sausage
      rolls, corned beef sandwiches, and sausages. The investigation of this outbreak
      illustrated the difficulty that elderly people may have in the completion of
      questionnaires. It also highlighted areas for intervention; such as reminders
      about basic hygiene precautions to prevent secondary spread and the importance of
      coordinated reinforcement in the workplace of formal food hygiene training for
      cooks. The Food Safety Regulations 1995 came into force soon after this outbreak:
      their implementation would probably have prevented it.

PMID- 9782632
TI  - An outbreak of Salmonella agona infection associated with precooked turkey meat.
AB  - An outbreak of Salmonella agona phage type (PT) 15 infection in North
      Staffordshire in September 1996 was associated with consumption of precooked
      turkey meat. The shops from which five of the six cases had bought turkey meat
      were supplied by the same distributor. S. agona phage type 15 was isolated from
      nine cases, from cooked turkey sampled from a shop, and from an unopened
      cryovacuumed packed joint at the supplier's premises. Environmental
      investigations at a food manufacturer's premises revealed deficiencies in cooking
      practices. Microbiological investigations at those premises on samples (food,
      environmental swabs) taken two to three weeks after the cases became ill were
      negative. The rarity of S. agona brought this outbreak to our attention and the
      successful identification of a vehicle of infection demonstrated the value of
      local surveillance of gastrointestinal pathogens and of good working
      relationships between public health and local authority staff. The prompt
      voluntary withdrawal of suspect product probably prevented further cases.

PMID- 9782633
TI  - A large outbreak of Q fever in the West Midlands: windborne spread into a
      metropolitan area?
AB  - The largest outbreak of the zoonotic disease Q fever recorded in the United
      Kingdom (UK) occurred in Birmingham in 1989. One hundred and forty-seven cases
      were identified, 125 of whom were males, and 130 of whom were between 16 and 64
      years of age. Fewer cases of Asian ethnic origin were observed than expected (p <
      0.01), and more smokers (p < 0.005). A case control study (26 cases and 52
      matched controls) produced no evidence that direct contact with animals or animal
      products had caused the outbreak. The epidemic curve suggested a point source
      exposure in the week beginning 10 April. The home addresses of cases were
      clustered in a rectangle 11 miles (18.3 km) north/south by 4 miles (6.7 km) east/
      west, and attack rates became lower towards the north. Directly south of this
      area were farms engaged in outdoor lambing and calving, a potent source of
      coxiella spores. A retrospective computerised analysis showed that the
      geographical distribution of cases was associated with a source in this area (p <
      0.00001). On 11 April, unusual southerly gales of up to 78 mph (130 km/h) were
      recorded. The probable cause of the outbreak was windborne spread of coxiella
      spores from farmland to the conurbation.

PMID- 9782634
TI  - Modification of the standard method used in the United Kingdom for counting
      Escherichia coli in live bivalve molluscs.
AB  - The standard method for counting Escherichia coli in live bivalve molluscs is
      labour intensive and takes three days to obtain a result. Modifications to the
      standard method were investigated in a collaborative trial conducted in five
      centres. No significant difference was found between results based on the
      presence of acid at 24 hours (h) in first stage tests and those based on the
      presence of acid and gas after 48 h (standard method). The use of the chromogenic
      medium BCIG (5-bromo-4-chloro-3-indolyl-beta-D glucuronide) agar incubated at 44
      degrees C to confirm first stage tests was also found to give equivalent results
      to conventional confirmation tests. The preferred, modified method removes the
      presence of gas as a criterion of detection, uses a chromogenic agar medium to
      confirm the presence of E. coli, and gives results within 48 h. A distribution of
      simulated samples and selected strains of E. coli to other laboratories using the
      PHLS external quality assurance scheme for shellfish found no significant
      difference between results obtained by the standard and modified methods.

PMID- 9782635
TI  - Active surveillance of sexual behaviour among homosexual men in London.
AB  - The objective of this study was to establish a surveillance programme to monitor
      high risk sexual behaviour among homosexual and bisexual men socializing and/or
      using health care services in London. Between November 1996 and January 1997 a
      brief, self-completed questionnaire was distributed in various commercial venues
      (bars, clubs, and saunas) and genitourinary medicine (GUM) clinics in inner
      London. A total of 2482 questionnaires were returned (response rate 75%). A third
      of men (32%) reported having had unprotected anal intercourse in the previous
      year and 18% had done so with one or more partners of unknown or different HIV
      status. High risk sexual behaviour was associated with younger age, having casual
      partners, and recruitment from GUM clinics. The combination of high levels of
      both sexual risk behaviour and HIV prevalence demonstrates the need for sustained
      and innovative health promotion campaigns among homosexual men in London.

PMID- 9782636
TI  - Parainfluenza virus and respiratory syncytial virus infection in infants
      undergoing bone marrow transplantation for severe combined immunodeficiency.
AB  - Respiratory syncytial virus and parainfluenza virus infection carry a poor
      prognosis in severe combined immunodeficiency (SCID), particularly if the viral
      load is high. Patients with high viral load develop severe pneumonitis at
      engraftment which may possibly be modulated by immunotherapy, including high dose
      nebulised corticosteroids. Further work is required to develop effective
      treatment for this severe condition.

PMID- 9782637
TI  - Scombrotoxic (histamine) fish poisoning in the United Kingdom: 1987 to 1996.
AB  - Between 1987 and 1996 fresh tuna and canned tuna contaminated after processing
      became increasingly associated with incidents of scombrotoxic fish poisoning.
      Fish not commonly associated with this syndrome were implicated in several
      incidents. Awareness of bacterial contamination after processing has highlighted
      the need for submitted samples to be examined both microbiologically and
      toxicologically and for the potential role of other toxins in this syndrome to be
      considered. The overall rate of reported incidents of scombrotoxic fish poisoning
      remained stable.

PMID- 9782638
TI  - An evaluation of Vitek--an automated system for bacterial identification and
      susceptibility testing.
AB  - We evaluated the Vitek system for bacterial identification and susceptibility
      testing with reference to its speed, staffing requirements, user friendliness,
      and data management. Its performance was satisfactory in all these dimensions,
      but it is expensive.

PMID- 9782639
TI  - A user's guide to producing and interpreting tree diagrams in taxonomy and
      phylogenetics. Part 3. Using restriction fragment length polymorphism patterns of
      bacterial genomes to draw trees.

PMID- 9782640
TI  - Home-grown computer systems solve laboratories' IT problems.

PMID- 9782641
TI  - TRIUMPH over adversity.

PMID- 9782642
TI  - Accident investigation.

PMID- 9782643
TI  - Report guides prescribing to the Path of Least Resistance.

PMID- 9782644
TI  - Sentinel surveillance shows small decline in MMR coverage.

PMID- 9782645
TI  - Encephalitis in the first three years of life.

PMID- 9782646
TI  - AIDS and HIV infection in the United Kingdom: monthly report.

PMID- 9782647
TI  - Children and managed health care: analysis and recommendations.

PMID- 9782648
TI  - Managed care and children: an overview.
AB  - This article lays the foundation for the other articles in this journal issue,
      which examine the effect of managed health care arrangements on a particular
      population: children. Although managed care has been used to finance and deliver
      health care services for decades, the meaning of this term often has been unclear
      to health care consumers and practitioners because new forms of managed care have
      evolved rapidly. The one consistent and unifying concept across all managed care
      arrangements is that enrollees obtain care from a network of participating health
      care providers who contract with the managed care organization and abide by the
      organization's rules. The uncertainty of what managed care is has made it
      difficult to measure the effect of these arrangements on health service delivery
      and health outcomes, especially in the pediatric population, where the
      development of outcome and quality measures lags behind that for adults. The
      incentives posed by managed care suggest both potential advantages and
      disadvantages to these arrangements for children. On the positive side, managed
      care enrollment may offer a "medical home" for primary care services to children
      who otherwise would obtain only episodic care; improve the coordination of health
      care services; and encourage more preventive health services. On the negative
      side, under capitated reimbursement, health plans have an incentive to enroll
      only healthy children with the lowest expected health care expenditures, and
      providers have an incentive to offer fewer services than may be appropriate.
      Managed care also may limit enrollees' choice of providers, particularly for
      specialty care. Despite the paucity of information about the effect of managed
      care on the delivery of pediatric health services and on child health outcomes,
      children are disproportionately being enrolled in managed care plans.

PMID- 9782649
TI  - Managed care for children: effect on access to care and utilization of health
      services.
AB  - The rapid trend toward enrolling children in managed care has occurred largely
      without conclusive evidence about the effects of these arrangements on two
      important aspects of care: access and utilization. Although the effect of managed
      care on these measures has been studied more widely in the adult population, the
      results may not be applicable to children, who have unique health care needs
      centering around prevention and early treatment of acute illnesses to avoid long
      term health problems. Moreover, several methodological challenges make it
      difficult to evaluate the impact of managed care on health care access and
      utilization in general. This article reviews what is known about the effect of
      managed care on access to health services, as well as utilization of hospital
      care, emergency department (ED) visits, primary care services, and specialty
      services for the pediatric population. In each area, findings from privately
      insured children and Medicaid enrollees are considered separately. There is
      little conclusive evidence on the effect of managed care on access to and
      utilization of pediatric health services. A recurring theme is that the effect of
      managed care is dependent on several factors, including whether providers assume
      financial risk through capitated reimbursements or retain fee-for-service
      payments; the comprehensiveness of benefits offered by health plans; and the
      level of cost sharing required of families. Among privately insured children, for
      example, managed care usually has been associated with higher primary care visit
      rates, though the benefit of managed care is reduced when fee-for-service plans
      cover preventive care and require minimal or no cost sharing for these services.
      Among Medicaid recipients, studies suggest that managed care is more likely to be
      associated with a decrease in preventive visits when provider payments are
      capitated. Attempts to decipher effects by health plan type are made more
      difficult by the rapid evolution of both managed care and fee-for-service plans,
      which often blurs the distinction between these two entities. Nonetheless, in
      some areas, managed care does appear to have an identifiable effect on pediatric
      health services. For Medicaid recipients, managed care has been associated with
      decreased emergency department use and decreased access to specialty care for
      chronically ill children. As enrollment of children in managed care plans
      increases, the need continues for methodologically sound studies evaluating the
      effect of these arrangements on the delivery of pediatric health services and on
      health outcomes.

PMID- 9782651
TI  - State regulation of managed care: the impact on children.
AB  - As more and more children enroll in managed care, states have responded to
      concerns expressed by their constituents by passing legislation and developing
      credentialing requirements to assist families with children in receiving
      appropriate care from managed care plans. Although most of the legislation and
      credentialing requirements apply to the population generally, a few provisions
      apply specifically to children. The legislation and credentialing requirements
      attempt to improve both access to medical care and the quality of care by
      enacting access-to-care and quality-of-care provisions, reducing the financial
      incentives for providers to offer inappropriate care, and providing families with
      more information about their choices and opportunities to redress their
      grievances. Although there is no empirical evidence, analysis of similar types of
      legislation suggests that certain approaches will be more successful than others;
      one obvious indicator of success is the ability of the regulatory agency to
      develop clear, unambiguous, enforceable rules. Existing legislation varies widely
      across states in terms of the issues addressed and the specificity of the laws.
      For the most part, this legislation has been piecemeal, addressing specific
      issues as they arise. In the long run, state legislatures may not have the time
      or the expertise to regulate the managed care industry, and other regulatory
      bodies may be better equipped to address concerns about managed care. If
      utilized, however, existing regulatory bodies, which historically monitored fee
      for-service medicine, will need to be redesigned to monitor managed care.

PMID- 9782650
TI  - Managed care and the quality of children's health services.
AB  - Managed care has changed the practice of medicine. The choice of health care
      providers has been narrowed, physicians are being held financially accountable
      for the number of services they use, and a new emphasis is being placed on the
      cost and quality of the care provided. The transition to managed care has
      occurred with little attention to its impact on access to health care services or
      the quality of services provided. There is an absence of information about how
      children fare in these new systems. What little is known indicates that children
      in managed care arrangements are less likely to be able to be seen by pediatric
      specialists, and that families and providers are less satisfied under managed
      care. The impact of these changes on children's health status, however, is yet to
      be determined. For children with special needs, the problems of coordination of
      care, coverage of needed services, and the choice of the appropriate pediatric
      subspecialists, many of which existed in traditional fee-for-service systems,
      persist under managed care. In spite of all of the negative anecdotes about
      managed health care, managed care's focus on its population of enrollees and its
      heightened sense of a need for health care accountability bring exciting new
      opportunities to measure and improve the health care children receive. A new
      emphasis is being placed on practicing evidence-based medicine; the focus is on
      closing the gap between what is known (effective, evidence-based care) and what
      is done (current practice). Improved health outcomes and reduced health care
      costs have been documented in demonstration projects in neonatal intensive care
      units and in pediatric offices. Applying the principles of these learning
      collaboratives and employing the tools of continuous quality improvement in
      health care are urgent challenges that deserve to be met. Health plans,
      physicians, health care purchasers, regulators, families, and their children must
      work together to assure that children receive the highest-quality care possible-
      care that is technically excellent and medically appropriate, and that improves
      the health of our children.

PMID- 9782652
TI  - Medicaid managed care and children: an overview.
AB  - In recent years, states have increasingly turned to managed care arrangements for
      financing and delivering health services to Medicaid beneficiaries. In 1996,
      approximately 40% of all Medicaid recipients were enrolled in some form of
      managed care. The rapid escalation of managed care in this population has been
      fueled by states' desire to slow the growth of Medicaid expenditures and by the
      trend toward managed care enrollment in the private health insurance industry.
      The effect of managed care on cost containment in the Medicaid program may be
      limited, however, because 85% to 90% of Medicaid managed care enrollees are women
      of childbearing age and children, who together account for 69% of Medicaid
      recipients, but only 26% of program costs. Nonetheless, the increase in managed
      care enrollment in this population may have a profound impact on health service
      delivery and health outcomes for U.S. children, approximately 20% of whom
      received health benefits through the Medicaid program in 1995. In the future, the
      proportion of Medicaid-eligible children enrolled in managed care will likely
      increase as a result of recent legislation that relaxed the requirement that
      states seek federal approval prior to mandating managed care enrollment for
      Medicaid beneficiaries. More states are relying on fully capitated arrangements
      as the preferred type of managed care for Medicaid recipients, despite the
      relative lack of experience many of these plans have in serving this low-income
      population. Moreover, managed care organizations have few incentives to enroll
      chronically or disabled children with higher-than-average expected costs. Without
      mechanisms in place that adequately adjust capitated rates to account for these
      higher-cost enrollees, managed care organizations may lose money, and children
      with the greatest health care needs may be underserved. As mandatory managed care
      enrollment for Medicaid recipients increases nationwide, states should carefully
      monitor changes in program costs and quality as well as implications for the
      delivery of pediatric health services and health outcomes.

PMID- 9782653
TI  - Improving state Medicaid contracts and plan practices for children with special
      needs.
AB  - The rapid transition of state Medicaid beneficiaries into fully capitated managed
      care plans requires a special focus on children with chronic or disabling
      conditions, who often depend on numerous pediatric physicians and other specialty
      services for health care and related services. Because managed care arrangements
      for this population are growing in popularity nationwide, it is important that
      states craft managed care contracts to address the unique needs of children with
      complex physical, developmental, and mental health problems. Based on the
      research reported in this article, in-depth interviews with state Medicaid agency
      staff, interviews with medical directors and administrators of managed care plans
      serving Medicaid recipients, and input from experts in pediatrics and managed
      care, a set of recommendations is made for tailoring managed care contracts to
      meet the needs of this vulnerable group of children. Six contracting elements
      that should be adopted by state Medicaid agencies include (1) clarifying the
      specificity of pediatric benefits, (2) defining appropriate pediatric provider
      capacity requirements, (3) developing a medical necessity standard specific to
      children, (4) identifying pediatric quality-of-care measures, (5) setting
      appropriate pediatric capitation rates, and (6) creating incentives for high
      quality pediatric care. Nine approaches that should be adopted by managed care
      practices interested in providing high-quality care for children with special
      needs also are identified. These include (1) ensuring that assigned primary care
      providers have appropriate training and experience, (2) offering support systems
      for primary care practices, (3) providing specialty consultation for primary care
      providers, (4) establishing arrangements for the comanagement of primary and
      specialty pediatric services, (5) arranging for comprehensive care coordination,
      (6) establishing flexible service authorization policies, (7) implementing
      provider profiling systems that adjust for pediatric case mix, (8) creating
      financial incentives for serving children with special needs, and (9) encouraging
      family involvement in plan operations. Implementing these changes to managed care
      contracting could have a major impact on the quality and comprehensiveness of
      health care received by children with special needs. Successful implementation,
      however, requires strong support from both state Medicaid agencies and the
      managed care plans dedicated to serving this population.

PMID- 9782655
TI  - Two commentaries: defining the challenge and opportunities for children in
      managed health care.

PMID- 9782654
TI  - The impact of managed care on mental health services for children and their
      families.
AB  - For more than a decade, the philosophy of community-based systems of care has
      guided the delivery of mental health services for children and adolescents served
      by publicly funded agencies. This philosophy supports system attributes that
      include a broad array of services; interagency collaboration; treatment in the
      least-restrictive setting; individualized services; family involvement; and
      services responsive to the needs of diverse ethnic and racial populations. The
      notion of systems of care emerged in an era when managed health care also was
      gaining popularity. However, the effect of managed care on the delivery of mental
      health and substance-abuse services--also known as behavioral health services-
      has not been widely studied. Preliminary results from the nationwide Health Care
      Reform Tracking Project (HCRTP) inform discussions about the impact of managed
      behavioral health care on services for children and adolescents enrolled in state
      Medicaid programs. Most states have used some type of "carve-out design" to
      finance the delivery of behavioral health services, and there is a trend toward
      contracting with private-sector, for-profit companies to administer these
      benefits. In general, managed care has resulted in greater access to basic
      behavioral health and community-based services for children and adolescents,
      though access to inpatient hospital care has been reduced. Under managed care, it
      also has been more difficult for youths with serious emotional disorders, as well
      as the uninsured, to obtain needed services. With managed care has come a trend
      toward briefer, more problem-oriented treatment approaches for behavioral health
      disorders. A number of problems related to the implementation of managed
      behavioral health care for children and adolescents were illuminated by the
      HCRTP. First, there is concern that ongoing efforts to develop systems of care
      for youths with serious emotional disorders are not being linked with managed
      care initiatives. The lack of investment in service-capacity development, the
      lack of coordination with other agencies serving children with behavioral health
      problems, and cumbersome preauthorization requirements that may restrict access
      to appropriate service delivery were other concerns raised by respondents about
      managed care. As the adoption of managed behavioral health care arrangements for
      Medicaid beneficiaries expands rapidly, the HCRTP will continue to analyze how
      this trend has affected children and adolescents with behavioral health problems
      and their families.

PMID- 9782656
TI  - Missing children.

PMID- 9782657
TI  - The State Children's Health Insurance Program (CHIP).

PMID- 9782658
TI  - Children and managed health care. A selected bibliography.

PMID- 9782660
TI  - Drinking in college: the politics of research and prevention.

PMID- 9782661
TI  - Changes in binge drinking and related problems among American college students
      between 1993 and 1997. Results of the Harvard School of Public Health College
      Alcohol Study.
AB  - In 1997, the Harvard School of Public Health College Alcohol Study resurveyed
      colleges that participated in a 1993 study. The findings revealed little change
      in binge drinking: a slight decrease in percentage of binge drinkers and slight
      increases in percentages of abstainers and frequent binge drinkers. Two of 5
      students were binge drinkers (42.7%); 1 in 5 (19.0%) was an abstainer, and 1 in 5
      was a frequent binge drinker (20.7%). As was true in 1993, 4 of 5 residents of
      fraternities or sororities were binge drinkers (81.1%). Asian students showed a
      greater increase and White students a greater decrease in binge drinking from
      1993 to 1997, compared with all other students. Among students who drank alcohol,
      increases in frequency of drinking; drunkenness; drinking to get drunk; and
      alcohol-related problems, including drinking and driving, were reported. Binge
      drinkers in both 1993 and 1997 were at increased risk of alcohol-related
      problems, and nonbingers at colleges with high binge drinking rates had increased
      risks of encountering secondhand effects of binge drinking.

PMID- 9782662
TI  - Evaluation of an STD-prevention program for Swedish university students.
AB  - The authors evaluated a sexually transmitted disease (STD)-prevention program
      that combined a mass media campaign with peer education. The program was designed
      to increase Swedish university students' knowledge about STDs, improve attitudes
      toward condom use, and tell students where to get an STD checkup. Preintervention
      and postintervention postal questionnaires wer used with an intervention group
      and two types of control groups. Responses ranged from 32% to 67% for the
      randomly selected students and from 93% to 99% for classroom and clinic
      participants. The intervention was noticed by a majority of the students (85-98%)
      and discussed by 43% to 57%; more women than men observed and discussed the
      campaign. Knowledge about STDs, where to turn for STD checkups, and the intention
      of having an STD checkup increased. Attitudes toward condom use were equally
      positive before and after the intervention. Although it was successful in
      attracting attention and leading to discussion of STD prevention, the campaign
      did not encourage students to have an STD checkup.

PMID- 9782663
TI  - Sources of error and nutritional adequacy of the food guide pyramid.
AB  - The authors assessed the accuracy of college students' use of the Food Guide
      Pyramid (FGP) in their diets and evaluated sources of error and nutritional
      adequacy of the pyramid. Students enrolled in an undergraduate nutrition class (N
      = 346) completed 3-day dietary records that were analyzed, using computer
      software, to determine individual recommended dietary allowance (RDA) values and
      the extent to which the students' diets met those values. The students' most
      common error in using the FGP was underestimating serving sizes. Only 8% of the
      students consumed the minimum recommended number of servings for all food groups,
      but diets that satisfied FGP recommendations also tended to satisfy RDA
      requirements. Less than 2% of the students who met the minimal number of FGP
      servings did not satisfy their RDA values, but less than 45% of the survey
      participants, regardless of gender or residence, met the recommended intake for
      dietary fiber. The FGP was judged to be a good indicator of dietary adequacy.

PMID- 9782664
TI  - Psychological readiness of black college students to be physically active.
AB  - Black students' psychological readiness to be physically active was examined in
      212 1st-year students (79 men and 133 women) at a historically Black university
      in the South. The students responded to the Physician-based Assessment and
      Counseling for Exercise (PACE) survey, which asked students about current
      physical activity habits. More men (57%) than women (32%) were classified as
      being in the action stage. Approximately 37% of the men in the sample, compared
      with 63% of the women, were in the contemplation stage, and 6% of the men and 5%
      of the women were classified as precontemplators. The findings indicated that
      health professionals need to provide interventions aimed at increasing the
      physical activity of Black students, especially women.

PMID- 9782665
TI  - Thinking about students who do not identify as gay, lesbian, or bisexual, but....

PMID- 9782666
TI  - The American College Health Foundation: lasting support for ACHA's mission.

PMID- 9782667
TI  - Sexual victimization: analyzing the analysis.

PMID- 9782668
TI  - Earthquake-induced cardiovascular disease and related risk factors in focusing on
      the Great Hanshin-Awaji Earthquake.
AB  - The major earthquake increases cardiovascular disease during the period from
      night-time to morning, especially in the elderly patients living around the
      epicenter. Earthquake-induced stress increased BP and blood viscosity
      determinants, and enhanced fibrin turnover with endothelial cell stimulation in a
      group of hypertensive elderly subjects. Earthquake might trigger the
      cardiovascular events through the potentiation of these acute risk factors.
      Reduction of stress and related acute risk factors in this period may suppress
      cardiovascular deaths following a major earthquake. Further investigation of the
      mechanisms triggering cardiovascular events after the a major event such as a
      major earthquake is a necessary part of the strategy for the prevention of
      cardiovascular disease.

PMID- 9782669
TI  - An optimal cutoff point of expired-air carbon monoxide levels for detecting
      current smoking: in the case of a Japanese male population whose smoking
      prevalence was sixty percent.
AB  - An optimal cutoff point of expired-air carbon monoxide (Ex-CO) for detecting
      smokers should be determined in terms of its sensitivity and specificity and the
      prevalence of smoking in the target population. The purpose of this study is to
      determine the optimal cutoff point of Ex-CO for detecting smoking males in a
      Japanese community whose smoking prevalence was over 50%. Among free-living
      residents in a rural population, "true smokers" determined by presence of
      cotinine in serum were 61% (n = 94). When Ex-CO at 7 ppm or over differentiated
      "smokers" from "non-smokers", sensitivity and specificity for detecting smokers
      was 0.93 and 0.95, respectively, which comprised the best Youden's index. This
      setting also produced the minimum percentage of misclassified cases. In
      conclusion, 7 ppm of Ex-CO, which is exceptionally low value relative to the
      western standard, appears to be the most optimal cutoff point for a survey in a
      population with such high smoking prevalence.

PMID- 9782670
TI  - Effects of passive smoking on serum levels of carotenoids and alpha-tocopherol.
AB  - To evaluate the effects of passive smoking identified by urine cotinine on serum
      carotenoids and alpha-tocopherol, we categorized 124 residents in a rural city of
      Japan into 4 groups by their urine cotinine/creatinine (Cot/Cr) ratio (u.d.
      (undetectable); low (0-50 ng/mg); moderate (50-120 ng/mg); high (> 120 ng/mg))
      and compared the serum carotenoids and alpha-tocopherol levels among these
      groups. We identified passive smoking by low Cot/Cr ratio level. After
      controlling on related factors, men with low Cot/Cr ratio showed significantly
      lower serum zeaxanthin/lutein levels than men with u.d. Cot/Cr ratio. The
      difference was still marginally significant after excluding self-reported current
      smokers from the low Cot/Cr group. It is suggested that low level exposure to
      tobacco smoke, which has been reported to be equivalent to that for passive
      smokers, could be associated with decreased serum zeaxanthin/lutein levels in
      men.

PMID- 9782671
TI  - Reliability and validity of a questionnaire for assessment of energy expenditure
      and physical activity in epidemiological studies.
AB  - A self-administered physical activity questionnaire (PA-questionnaire) was
      developed to assess daily energy expenditure and weekly physical activity in
      epidemiological studies. The Calorie Counter method (CC-method) was administered
      to 49 male and 32 female volunteers aged 18-64 years, on 7 consecutive days;
      after the measurement, the subjects were asked to complete the PA-questionnaire
      (validation study). The PA-questionnaire was completed by 95 males and 119
      females (aged 35-73 years) twice with one-year interval (reliability study). The
      validation study showed that the mean daily energy expenditure estimated by the
      PA-questionnaire was slightly and significantly (4.5%) lower than that determined
      by the CC-method for males (p < 0.05); while no significant difference was
      observed for females (p > 0.05), mean weekly physical activities were similar
      between the PA-questionnaire and CC-method in males and females. Daily energy
      expenditures by the two methods strongly correlated with each other: r = 0.56 (p
      < 0.001) in males and r = 0.67 (p < 0.001) in females. Weekly physical activities
      by the two methods also strongly correlated with each other: r = 0.68 (p < 0.001)
      in males and r = 0.69 (p < 0.001) in females. The reliability study indicated
      that the Pearson's correlation coefficients between two assessments of daily
      energy expenditure and weekly physical activity over one-year ranged from 0.37 to
      0.62 (p < 0.001). These data indicate that the PA-questionnaire has adequate
      levels of validity and test-retest reliability in assessment of daily energy
      expenditure and weekly physical activity in epidemiological studies.

PMID- 9782672
TI  - Trends of average intake of macronutrients in 47 prefectures of Japan from 1975
      to 1994--possible factors that may bias the trend data.
AB  - To describe the geographical patterns and trends of macronutrient intake in Japan
      for the recent 20 years, we analyzed the data sets of the National Nutrition
      Surveys (J-NNS). First, we calculated regression coefficients for survey year by
      prefecture for energy, protein, fat, and carbohydrate intake. These results,
      however, could be affected by the changes in age and sex distributions of the
      survey samples. Secondly, as the food consumption data were based on household as
      a unit, we used proportions of the subjects who belong to age-specific groups and
      female subjects in a sub-sample for each prefecture in a given year for
      adjustment by general lineal model. As a result, 1% increase in the subjects aged
      1-4, 10-19 and 65- years and female subjects was equivalent to the changes in
      average energy intake by -5.88, +2.27, -1.45 and -1.62 kcal, respectively. After
      the adjustment for age and sex, number of significant negative coefficients among
      47 prefectures decreased for energy and carbohydrate intake, and that of positive
      coefficients increased for fat intake. This suggested that unadjusted trend data
      might lead to an overestimation of decreasing trends of energy and carbohydrate
      intake, and an underestimation of increasing trend of fat intake in the recent 20
      years.

PMID- 9782673
TI  - Japanese intake of flavonoids and isoflavonoids from foods.
AB  - The intake of flavonoids and isoflavonoids was estimated based upon a preliminary
      database of 40 food items, covering at least 80% of total food consumption. Fifty
      volunteer women in "I-City" recorded the weight of all dietary intake for 3 days
      in September 1996, and received a health check-up, as well as laboratory
      examination. The data was analyzed in relation to the various food factors.
      Average daily intake per capita of flavonoids was as follows: 4.9 mg kaempferol,
      8.3 mg quercetin, 1.5 mg rutin, 0.6 mg myricetin, 0.3 mg luteolin, 0.01 mg
      myricitrin, 0.4 mg fisetin, and 0.3 mg eriodictyol. Total intake from vegetables
      and fruits was less than 10 mg 16.2 mg (range: 3.18-35.61 mg) and 23.27 mg (4.62
      52.12 mg) of isoflavones, such as daidzein and genistein, respectively, were
      taken per day, and total isoflavone intake was 39.46 mg (7.80-87.73 mg). Chief
      component analysis on ingested vitamins, flavonoids and isoflavonoids was carried
      out. Factor 1 was mainly composed of flavonoids and antioxidant vitamins. Factor
      1 was positively associated with age and the level of HDL cholesterol and
      negatively related to the level of triglycerides. Factor 2, which was mainly
      composed of isoflavonoids, was positively associated with creatinine and uric
      acid levels. So far, these factors did not show a significant association with
      bone density and other health indices, such as BMI and blood pressure.

PMID- 9782674
TI  - Body fat distribution and uterine leiomyomas.
AB  - PURPOSE: Investigation of the etiological relationship between body fat and
      uterine leiomyomas. SETTINGS: This was a case-control study. Percent body fat was
      measured bioelectrically with a body fat analyzer. SUBJECTS: In Sapporo City,
      Japan, 100 women with uterine leiomyomas (pathologically diagnosed) and 200
      controls who were confirmed to have no uterine leiomyomas by clinical
      examination. RESULTS: Among the four types classified by BMI (over/under 24.0)
      and percent body fat (over/under 30%), the occult obesity type (BMI < 24.0 and
      percent body fat > or = 30%) had the highest risk. There were no patients of
      muscular type (BMI > or = 24.0 and percent body fat < 30%). Women with more than
      0.80 of waist-to-hip ratio were also at significantly higher risk. CONCLUSIONS:
      Occult obesity and upper body fat distribution may lead to the development of
      uterine leiomyomas.

PMID- 9782675
TI  - Knowledge and practices about HIV/AIDS among the commercial sex workers in
      Bangladesh.
AB  - A survey on knowledge and practices of 228 Bangladeshi commercial sex workers
      (CSWs) concerning AIDS was conducted in the largest brothel in Narayangonj, 20 km
      from the capital Dhaka in September through December, 1993. Only 18% of the
      respondents heard about AIDS and 8% knew about its propensity to sexual
      transmission. AIDS was believed to be curable by 5% of the total respondents.
      None were regular condom users, but 8% said condom use could prevent HIV
      infection. Vigorous AIDS awareness campaigns for the CSWs and their clients,
      leading to regular condom use, is necessary to prevent an explosive epidemic in
      Bangladesh.

PMID- 9782676
TI  - A controlled study of peer relationships of children surviving brain tumors:
      teacher, peer, and self ratings.
AB  - OBJECTIVE: Evaluate the behavioral reputation and peer acceptance of children
      diagnosed and treated for brain tumors. METHOD: Twenty-eight children surviving
      brain tumors (8-18 years of age) were compared to 28 nonchronically ill, same
      classroom, same gender comparison peers (COMP). Peer, teacher, and self-report
      data were collected. RESULTS: Relative to COMP, children who had been diagnosed
      with brain tumors received fewer friendship nominations from clasmates and were
      described by peer, teacher, and self-report as socially isolated. Although they
      were no longer receiving therapy for their disease, peers perceived brain tumor
      survivors as being sick, more fatigued, and often absent from school.
      CONCLUSIONS: These data suggest that children surviving brain tumors are at risk
      for social difficulties even after treatment ends, although the specific cause(s)
      for this vulnerability were not investigated in the current study.

PMID- 9782677
TI  - Parent assessment of psychological and behavioral functioning following pediatric
      acquired brain injury.
AB  - OBJECTIVE: Compare the measured prevalence rate of psychopathology and behavior
      disorders in 29 children with acquired brain injuries using four parent-report
      instruments. METHOD: Two questionnaires, the Child Behavior Checklist (CBCL) and
      the Personality Inventory for Children (PIC-R) and two interview measures, the
      Diagnostic Interview for Children and Adolescents (DICA-R) and the Vineland
      Adaptive Behavior Scales (VABS), were completed following injury or diagnosis.
      RESULTS: The DICA-R identified the highest prevalence of anxiety disorders and
      acting-out behaviors, whereas the CBCL identified the lowest prevalence. Opposite
      results were found within the domain of attentional problems. Interview measures
      were more concordant for global psychological impairment than were
      questionnaires. DISCUSSION: Discordant findings across measures are discussed in
      terms of type of disorder, classification model, response format, item
      characteristics, and scaling.

PMID- 9782678
TI  - Psychological adjustment of adolescents with sickle cell disease: relations with
      demographic, medical, and family competence variables.
AB  - OBJECTIVE: Investigate the hypothesis that family competence in addressing
      challenges associated with sickle cell disease (SCD) contributes to adolescents'
      adjustment. METHOD: During routine clinic appointments, 80 adolescents (M age =
      14.4 years) and their parents independently completed the Self-Report Family
      Inventory (SFI), which assesses family competence, and measures of adolescent
      adjustment problems. Information related to disease severity was obtained from
      clinic files. RESULTS: Regression analyses controlling for demographic and
      medical variables revealed that higher family competence was associated with
      fewer internalizing and externalizing behaviors by the adolescent; these
      relations were particularly true for younger adolescents and for girls. Parental
      reports of somatic complaints in girls were predicted by parental ratings of
      family competence. DISCUSSION: Interventions for adolescents with SCD should be
      family-centered and should focus on strengthening the family's ability to manage
      stressors associated with parenting an adolescent with a chronic illness.

PMID- 9782679
TI  - The highly structured climate in families of adolescents with diabetes:
      functional or dysfunctional for metabolic control?
AB  - OBJECTIVE: Compare changes in perceived family climate over time in families with
      healthy adolescents and families with adolescents with diabetes and analyze the
      links to metabolic control. METHOD: In a total of four annually conducted
      surveys, 89 German adolescents with diabetes and 106 healthy adolescents as well
      as their parents completed the Family Environment Scale (FES). Metabolic control
      was determined by physicians' reports of adolescents' hemoglobin (HbA1) levels.
      RESULTS: Compared to families with healthy adolescents, families caring for an
      adolescent with diabetes portrayed their family interactions as considerably more
      structured and less cohesive and stimulating. Family climate was not associated
      with metabolic control and varied little with time, illness duration, and
      adolescents' gender. CONCLUSIONS: The findings suggest that continued parental
      monitoring is necessary for good metabolic control. However, a balance must be
      found between medical adaptation to illness and the adolescent's developmental
      needs.

PMID- 9782680
TI  - School-age children's attributions about their own naturally occurring minor
      injuries: a process analysis.
AB  - OBJECTIVE: To analyze children's attribution of cause regarding their naturally
      occurring minor injuries in light of the pre-injury parental acceptability of
      children's behavior and the emotions children experienced immediately after the
      event. METHOD: Sixty-one 8-year-old children were interviewed biweekly for one
      year about their naturally occurring minor injuries. Participants monitored
      environmental and psychosocial elements of the injuries and later answered
      questions about the cause of the event. RESULTS: For a total sample of 1,037
      minor injuries, children most frequently designated fate as the primary cause.
      Further analysis revealed that attributions varied by children's pre-injury
      behavior and post-injury feelings. Children were equally likely to accept primary
      responsibility or to assign cause to fate when they were engaged in unacceptable
      behavior before the event. Similarly, children assumed primary responsibility for
      the injury when they experienced post-injury guilt. No differences in injury
      attributions were revealed by gender or by the child's frequency of injuries
      during the year. CONCLUSIONS: Results highlight the significance of adult
      caregiver safety rule creation, endorsement, and ongoing communication for the
      socialization of children's safe behaviors.

PMID- 9782682
TI  - Oral 5-HT3-receptor antagonists: expanding the options for Medicare outpatients.

PMID- 9782683
TI  - Innovation at Midwestern.

PMID- 9782681
TI  - Cognitive and academic late effects among children previously treated for acute
      lymphocytic leukemia receiving chemotherapy as CNS prophylaxis.
AB  - OBJECTIVE: Examine cognitive and academic late effects among children and
      adolescents who had received central nervous system (CNS) prophylactic
      chemotherapy alone for acute lymphocytic leukemia (ALL); none had received whole
      brain radiation therapy (RT). METHOD: Subjects included 47 children and
      adolescents from 5 to 22 years of age who were treated on the same protocol and
      had been off treatment from 2 to 7 years at the time of assessment. RESULTS: As a
      group the survivors displayed generally average performance on measures of
      cognitive and academic abilities, although they differed from normative means on
      tests of nonverbal skills. Girls performed more poorly than the normative sample
      on nonverbal tasks, while no differences were found for boys. Age at diagnosis
      and time off treatment were not significantly associated with cognitive and
      academic functioning for survivors of this particular chemotherapy-only protocol.
      CONCLUSIONS: Data were interpreted to support generally modest potential late
      effects in specific areas for children and adolescents surviving ALL. These
      findings suggest a need for monitoring nonverbal cognitive skills for childhood
      survivors of ALL, particularly for girls.

PMID- 9782684
TI  - Regulating for pharmaceutical care outcomes.

PMID- 9782685
TI  - Profession: privilege and obligation.

PMID- 9782687
TI  - Pharmacy-based laboratory testing: adding another dimension to pharmaceutical
      care.

PMID- 9782686
TI  - Interim report from project ImPACT: hyperlipidemia.

PMID- 9782688
TI  - APhA drug treatment protocols: management of patients with generalized anxiety
      disorder.APha Psychiatric Disorders Panel.

PMID- 9782689
TI  - Developing and implementing pharmacy-based asthma services.

PMID- 9782690
TI  - Development, implementation, and evaluation of a multicenter pharmaceutical care
      outcomes study.
AB  - OBJECTIVES: To: (1) develop a pharmaceutical care multicenter outcomes research
      project using clinical pharmacy residents and preceptors; (2) develop two
      research protocols to document pharmacists' impact on clinical, economic, and
      humanistic outcomes of therapy; (3) develop and implement a data collection
      process and methodology for outcomes research; (4) evaluate the effectiveness of
      the multicenter outcomes research process; and (5) prepare clinical pharmacy
      preceptors and residents to conduct outcomes research. DESIGN AND SETTING: Two
      research protocols were developed, each a randomized, parallel, open-label
      evaluation of patients at 10 Department of Veterans Affairs and 1 university
      medical center. One protocol focused on patients with chronic obstructive
      pulmonary disease (COPD) and the other on patients with hypertension. The study
      evaluated pharmacists' management of these two patient groups. PATIENTS AND OTHER
      PARTICIPANTS: 133 patients with hypertension and 98 patients with COPD; 33
      pharmacy directors and preceptors; 45 pharmacy residents. MAIN OUTCOME MEASURES:
      Clinical, economic, and humanistic outcomes of pharmacists' interventions. The
      processes of developing a multicenter outcomes study were evaluated, including
      the data collection process. RESULTS: The two study protocols and an educational
      program for study participants were developed. A data collection process was
      developed and implemented, with the paper process being successful and the
      computer data collection process not implemented due to time constraints.
      Overall, the multicenter outcomes research process was successful. CONCLUSION:
      The study provides a framework of processes and sites for the future development
      of other outcomes research studies. Clinical, economic, and humanistic outcomes
      are reported in Parts 2 and 3.

PMID- 9782692
TI  - Humanistic outcomes in the hypertension and COPD arms of a multicenter outcomes
      study.
AB  - OBJECTIVE: To evaluate the effects of pharmaceutical care on selected humanistic
      outcomes in patients with hypertension or chronic obstructive pulmonary disease
      (COPD). DESIGN: Clinic patients with hypertension or COPD were randomly assigned
      to a treatment group (pharmaceutical care) or a control group (traditional
      pharmacy care) over a six-month period. Clinical pharmacists and pharmacy
      residents conducted the protocols. There were 133 evaluable patients (63
      treatment, 70 control) in the hypertension study arm and 98 evaluable patients
      (43 treatment, 55 control) in the COPD study arm. The Pharmaceutical Care
      Questionnaire evaluated patient satisfaction with care. Tests specific to the
      disease states assessed disease and disease management knowledge. Quality of life
      (QOL) was evaluated using the Health Status Questionnaire 2.0 (HSQ 2.0) in the
      COPD arm; in the hypertension arm, the Hypertension/Lipid TyPE Specification Form
      5.1 was used. SETTING: Ambulatory care centers of 10 Department of Veterans
      Affairs (DVA) medical centers and 1 university medical center. INTERVENTIONS:
      Patient-centered pharmaceutical care model (employing standardized care)
      implemented by clinical pharmacy residents. MAIN OUTCOME MEASURES: Satisfaction
      with pharmaceutical care, disease and disease management knowledge, and QOL.
      RESULTS: Statistically significant differences in most satisfaction items were
      found, with treatment patients expressing greater satisfaction. Treatment groups
      in both arms strongly agreed that pharmacists helped them with confidence in use
      of their medication and understanding of their illness, gave complete
      explanations about their medications, made them feel that their care was a
      priority, and followed up on their questions and concerns. In the hypertension
      arm, treatment patients demonstrated significant increases in knowledge scores.
      Trends in QOL were positive for both hypertension groups, with a significant
      decrease found in number of treatment patients reporting problems with sexual
      function. In the COPD arm, improvement trends were significantly stronger for
      treatment patients. CONCLUSION: Although patients were not dissatisfied with
      traditional pharmacy care, they were more satisfied overall with the
      pharmaceutical care model.

PMID- 9782691
TI  - Clinical and economic outcomes in the hypertension and COPD arms of a multicenter
      outcomes study.
AB  - OBJECTIVE: To evaluate the impact of pharmaceutical care on selected clinical and
      economic outcomes in patients with hypertension or chronic obstructive pulmonary
      disease (COPD) in ambulatory care settings. DESIGN: Clinic patients with
      hypertension or COPD were randomly assigned to a treatment group (pharmaceutical
      care) or a control group (traditional pharmacy care) over a six-month period.
      Clinical pharmacists and pharmacy residents conducted the protocols. There were
      133 evaluable patients (63 treatment and 70 control) in the hypertension study
      arm and 98 evaluable patients (43 treatment and 55 control) in the COPD study
      arm. SETTING: 10 Departments of Veterans Affairs medical centers and 1 academic
      medical center. INTERVENTIONS: Patient-centered pharmaceutical care model
      (employing standardized care) implemented by clinical pharmacy residents. MAIN
      OUTCOME MEASURES: Patient knowledge, medication compliance, and health resource
      use. RESULTS: The hypertension treatment group had a significantly greater
      reduction in systolic blood pressure from visit 1 to visit 5 than did the control
      group. In the COPD study arm, trends were positive in the treatment group for
      patients ratings of symptom interference with activities and dyspnea measures.
      There was a significant difference between the hypertension treatment and control
      group for compliance. There were no significant changes in compliance scores in
      the COPD study arm. Mean number of hospitalizations and other health care
      provider visits was higher for the hypertension control group. For patients with
      COPD, hospitalizations increased in the control group, and the number of other
      health care provider visits was higher in the control group. CONCLUSION:
      Pharmacists' participation in a pharmaceutical care program resulted in disease
      state improvement in ambulatory patients with hypertension and COPD.

PMID- 9782693
TI  - Community pharmacists as patient advocates: physician attitudes.
AB  - OBJECTIVES: To assess physician attitudes toward community pharmacists acting as
      patient advocates with respect to drug-related matters, and to correlate
      physician attitudes with physician characteristics and physician-pharmacist
      interactions. SETTING: State of Utah. PARTICIPANTS: Physicians in family
      practice, internal medicine, pediatrics, and psychiatry. INTERVENTIONS: Mail
      survey. MAIN OUTCOME MEASURES: Physician attitudes toward community pharmacists
      performing 15 patients advocacy activities, as well as physician-pharmacist
      interaction and respondent demographics. RESULTS: Favorable attitudes were
      identified for pharmacists monitoring drug use, counseling patients, advising
      physicians, contacting physicians to discuss patients' pharmacotherapy, and
      recording over-the-counter product use in patient profiles. Attitudes were less
      favorable toward pharmacists helping patients manage adverse drug reactions,
      suggesting drug regimen alterations, providing health screening services,
      selecting drugs by a protocol, discussing therapeutic equivalents with patients,
      and changing dosage forms to better suit patient needs. Physician age was
      negatively correlated with attitude toward a pharmacist aiding a physician in
      selecting a drug to be prescribed. The helpfulness of physician-pharmacist
      interactions was positively correlated with physician attitudes. CONCLUSION: From
      the physician's perspective, the most appropriate areas for expansion of the
      community pharmacist's role into patient advocacy are in monitoring
      pharmacotherapy, assisting physicians in coordinating pharmacotherapy, and
      providing patients with medication information. Physician resistance is more
      likely in areas where community pharmacists assume a more autonomous role in
      patient care.

PMID- 9782694
TI  - Use of alternative therapies and their impact on compliance: perceptions of
      community pharmacists in Texas.
AB  - OBJECTIVE: To assess community pharmacists' experiences with the use of
      alternative therapies by their patients with chronic illnesses. DESIGN: Mail
      survey. SETTING: State of Texas. PARTICIPANTS: 142 community independent and
      chain pharmacists. MAIN OUTCOME MEASURES: Pharmacists' recollections about
      patients' use of alternative therapies. RESULTS: Pharmacists estimated that 17%
      of their patients with chronic illnesses used some form of alternative therapy. A
      majority (66.9%) indicated that they have patients who used some type of
      alternative therapy for chronic conditions and that a majority (59.7%) of these
      patients consulted with them regarding those therapies. However, in only 11.1% of
      these cases did pharmacists document alternative therapy use in patients'
      pharmacy records. Pharmacists reported that 25.9% of these patients who use
      alternative therapies for chronic conditions were not compliant with their
      prescribed medication regimen. One-third (33.1%) of respondents indicated they
      knew of no patients who used alternative therapies, and 35.9% had never asked.
      CONCLUSION: Pharmacists need information on patients' use of alternative
      therapies for chronic illnesses to make valid therapy decisions and to monitor
      outcomes. Future research should identify actions that pharmacists take to
      address drug-related problems among alternative therapy users and assess the
      impact of these actions on drug therapy-related outcomes.

PMID- 9782696
TI  - Osteoporosis in women: prevention and treatment.
AB  - OBJECTIVE: To review osteoporosis, its pathophysiology, lifestyle and dietary
      factors that influence osteoporosis, and treatments to prevent and treat the
      disease in women. DATA SOURCES: MEDLINE using the search term osteoporosis and
      individual therapies and interventions for 1974-1988. STUDY SELECTION: English
      language studies in humans were reviewed. Prospective clinical trial data were
      selected when available; epidemiologic data were used when prospective clinical
      trials were not available. DATA SYNTHESIS: Pharmacists should initiate
      discussions with women of all ages to help prevent, recognize, and treat
      osteoporosis. Assessing and modifying calcium, vitamin D, caffeine, alcohol, and
      phosphate intake, increasing exercise, and minimizing falls can help prevent
      osteoporosis and fractures. The risks and benefits of hormone replacement therapy
      should be presented to women so they can make an informed decision. Hormone
      replacement therapy is the treatment of choice for preventing and treating
      osteoporosis; it also reduces cardiovascular morbidity and mortality. The
      benefits must be put into the proper perspective with adverse effects, events
      such as vaginal bleeding and the risk of breast cancer, that prevent women from
      taking estrogen. As not every woman is willing or able to take estrogen,
      alternatives should be discussed. Raloxifene prevents osteoporosis, has
      beneficial lipid effects, and does not stimulate breast or endometrial tissue.
      Alendronate is a safe and effective for the prevention and treatment of
      osteoporosis when administered properly. Calcitonin is approved for treatment of
      osteoporosis and provides analgesic effects for fractures. CONCLUSION:
      Pharmacists should initiate discussions with women of all ages to help prevent,
      recognize, and treat osteoporosis. Assessing and modifying calcium and vitamin D,
      caffeine, alcohol, and phosphate intake, increasing exercise, and minimizing
      falls can help prevent osteoporosis and fractures.

PMID- 9782695
TI  - Alcohol use, drug use, and sexual activity among pharmacy students at three
      institutions.
AB  - OBJECTIVE: To determine alcohol and drug use and sexual activity among pharmacy
      students at three colleges of pharmacy. DESIGN AND SETTING: A survey to obtain
      self-reported information on alcohol and drug use, and sexual activity was
      administered to professional pharmacy students at the University of Iowa (UI),
      Massachusetts College of Pharmacy, and Texas Southern University. MAIN OUTCOME
      MEASURES: Information on sexual activity and condom use, alcohol and drug
      consumption, and the effect of alcohol on unintended sexual activity. RESULTS:
      848 students (50% response rate) completed the survey. Alcohol use was high at
      all three institutions, and most students had consumed five or more drinks on one
      or more occasions within the last three months. The extent of drug use among
      pharmacy students was similar to that reported in other college students. The
      majority of students were sexually active. More men than women reported having
      been sexually active with one or more partners. Most students reported having had
      sexual intercourse without a condom. Significant numbers of students had engaged
      in unintended sex after alcohol use, especially at UI (chi 2 = 12.6, p = 0.002).
      Sexual contact and drinking were strongly correlated (Pearson r = 0.31, p =
      0.0001). CONCLUSION: Alcohol consumption among pharmacy students was high. Heavy
      drinking (five or more drinks on one occasion) was associated with unintended
      sexual contact. Given low condom use and increased sexual contact, pharmacy
      students are at an increased risk for HIV infection. Strategies should be
      developed to reduce alcohol intake and unprotected sexual activity among pharmacy
      students.

PMID- 9782697
TI  - Planning for new pharmacy services.

PMID- 9782698
TI  - Use of Regranex gel for diabetic foot ulcers.

PMID- 9782699
TI  - Gabapentin and lamotrigine in the treatment of bipolar disorder.

PMID- 9782700
TI  - Many ways to contract hepatitis B, one key way to prevent it.

PMID- 9782701
TI  - IBC fee schedule revisions prompt rebuttal.

PMID- 9782702
TI  - Physician advocacy addressed by division of representation.

PMID- 9782703
TI  - Managed care reform ... ground zero.

PMID- 9782704
TI  - Patient protections stalled in Congress.

PMID- 9782706
TI  - AMA house stands firm against E&M coding proposal.

PMID- 9782705
TI  - "Messenger model" of negotiation stirs controversy.

PMID- 9782707
TI  - Xact Medicare reports 68 percent coding error rate.

PMID- 9782708
TI  - Regaining control of health care delivery.

PMID- 9782709
TI  - Drug interactions with cytochrome P-450.

PMID- 9782710
TI  - Focus groups reveal physician views.

PMID- 9782711
TI  - Trust pilots self-directed distance learning program.

PMID- 9782712
TI  - Diabetes mellitus, everybody's disease.

PMID- 9782714
TI  - Diabetes in Florida.

PMID- 9782713
TI  - Targeted glycemic control in type 2 diabetes.

PMID- 9782715
TI  - Implications of the diabetes control and complications trial. American Diabetes
      Association.

PMID- 9782716
TI  - Nutrition recommendations and principles for people with diabetes mellitus.
      American Diabetes Association.
AB  - A historical perspective of nutrition recommendations is provided in Table 1.
      Today there is no one "diabetic" or "ADA" diet. The recommended diet can only be
      defined as a nutrition prescription based on assessment and treatment goals and
      outcomes. MNT for people with diabetes should be individualized, with
      consideration given to usual eating habits and other lifestyle factors. Nutrition
      recommendations are then developed and implemented to meet treatment goals and
      desired outcomes. Monitoring metabolic parameters, including blood glucose
      levels, glycated hemoglobin, lipids, blood pressure, body weight, and renal
      function, if appropriate, as well as quality of life, is crucial to ensure
      successful outcomes. Furthermore, it is essential that ongoing nutrition self
      management education and care be provided for individuals with diabetes.

PMID- 9782718
TI  - Health care quality improvement in Florida.

PMID- 9782717
TI  - Diabetes medical practice guidelines. State of Florida Agency for Health Care
      Administration. Diabetes Practice Guideline Advisory Committee.

PMID- 9782719
TI  - HCFA's health care quality improvement program and physicians.

PMID- 9782720
TI  - Quick results: clinical process improvement.

PMID- 9782722
TI  - Influenza immunization among Medicare beneficiaries enrolled in a health
      maintenance organization: 1994. Florida Medical Quality Assurance, Inc.

PMID- 9782721
TI  - Early management of acute stroke in emergency departments: preliminary findings.
      Florida Medical Quality Assurance, Inc.

PMID- 9782723
TI  - Angiotensin converting enzyme inhibitor use in congestive heart failure. Florida
      Medical Quality Assurance, Inc.

PMID- 9782724
TI  - On the horizon: newly-developed quality improvement projects. Florida Medical
      Quality Assurance, Inc.

PMID- 9782725
TI  - Hyperlipidemia management in patients with cardiovascular and cerebrovascular
      disease.

PMID- 9782726
TI  - Physician office-based quality improvement projects. Florida Medical Quality
      Assurance, Inc.

PMID- 9782727
TI  - [Central serous chorioretinopathy. Clinical, fluorescein angiography and
      demographic aspects].
AB  - The purpose of this retrospective study was to analyze the demographic
      characteristics of central serous chorioretinopathy (CSC). METHODS: Findings of
      100 consecutive subjects with CSC were evaluated. Clinical and fluorescein
      angiographic findings, demographic characteristics, and visual acuity were
      analyzed. RESULTS: The age of the patients ranged from 28 to 68 years with a mean
      of 43 years. No significant sex differences were found concerning age and other
      parameters. The highest age peak was in the group of women. The male to female
      ratio was 5:1. Patients with chronic CSC were significantly older (P = 0.015)
      than patients with the other angiographic findings. Median visual acuity was 0.5.
      In 40% bilateral characteristics of CSC were found. Clinical and fluorescein
      angiographic findings showed no significant correlation with visual acuity.
      CONCLUSION: The range of age distribution in CSC is wide. In older patients
      distinguishing CSC from age-related macular degeneration can be difficult.

PMID- 9782728
TI  - [Posterior pars plana high frequency capsulotomy].
AB  - In special forms of complicated secondary cataract, especially after a cataract
      operation in eyes with proliferative disease and after a cataract operation
      associated with pars plana vitrectomy and silicone oil instillation, surgical
      capsulotomy must be performed. METHODS: We developed a new surgical technique for
      posterior capsulorhexis via pars plana by using the high-frequency capsulotomy
      method developed by Kloti. We analyzed 14 consecutive patients undergoing late
      pars plana capsulotomy using a specially designed instrument for radiofrequency
      capsulorhexis. The indication for surgical capsulotomy was extreme secondary
      cataract; in 6 eyes fibrosis was associated with vascularizations. RESULTS: The
      high-frequency technique for posterior capsulotomy allowed reliable and precise
      tissue cutting. The cutting required minimal application of pressure to the
      capsule, and therefore damage to zonula fibers is minimized. Furthermore, use of
      the radiofrequency technique permitted hemostatic incision in vascularized
      membranes by inducing a fine coagulation margin. CONCLUSIONS: Posterior
      capsulorhexis using radiofrequency offers precise and effective tissue cutting if
      surgical capsulotomy is necessary.

PMID- 9782729
TI  - [Ab externo erbium YAG laser sclerostomy versus conventional trabeculectomy.
      Treatment of glaucoma patients].
AB  - PURPOSE: This study was conducted to compare the efficacy of the Er-YAG laser
      sclerostomy ab externo versus trabeculectomy in the treatment of primary open
      angle glaucoma. METHODS: Twelve patients with POAG underwent ab externo laser
      sclerostomy using an Er-YAG laser (Sklerostom 2.9; lambda = 2940 nm, t = 200
      microseconds, 2 Hz, 400 microns, 15 mJ). Only local medication was used, and
      there were no risk factors for failure. As a control group 12 patients out of 248
      standardized trabeculectomies were matched in terms of age, sex, diagnosis and
      local medications. No antimetabolites were used in either group. RESULTS: After a
      follow-up of 9 months in the sclerostomy group 53%; (7/12; P = 0.03) showed a
      patent fistula in comparison of 100% in the trabeculectomy group. There was a
      significantly lower mean IOP during the first postsurgical week in the group of
      sclerostomies (3.6 +/- 1.5 mmHg versus 7.5 +/- 2.7 mmHg; P = 0.0001) with a
      higher incidence of choroidal detachments (9/12 versus 2/12; P = 0.004). The
      choroidal detachments lasted longer in the sclerostomy group (3.5 months versus
      0.3 months; P = 0.014). Iris incarcerations were found only in sclerostomies
      (7/12; P = 0.05). CONCLUSIONS: Based on these findings, Er-YAG laser sclerostomy
      prooved to be less effective than trabeculectomy in the treatment of glaucoma
      patients. Er-YAG laser sclerostomies were associated with a higher incidence of
      postsurgical complications such as hypotony, choroidal detachments and iris
      incarcerations. At this point Er-YAG laser sclerostomy is not superior to
      conventional trabeculectomy.

PMID- 9782731
TI  - [Diagnostic error in Leber's optic neuropathy. Value of clinical and molecular
      genetic studies].
AB  - BACKGROUND: Leber's hereditary optic neuropathy is associated with point
      mutations in the mitochondrial DNA (mtDNA) that appear to be pathogenic for this
      disease. These mutations affect nucleotide positions 3460, 11,778 and 14,484.
      MATERIALS AND METHODS: We reviewed the clinical and molecular genetic
      characteristics of 29 visually symptomatic patients with the clinical diagnosis
      of LHON. RESULTS: Nine patients really suffered from LHON, but in 20 patients
      other ocular diseases could be proven. Degeneration of the retina and choroid was
      most common (seven patients), followed by vascular optic disease (six patients).
      Three patients suffered from tobacco-alcohol amblyopia, two from optic neuritis
      and two from autosomal dominant optic neuropathy. CONCLUSIONS: The clinical
      diagnosis of LHON is strengthened by a proven maternal inheritance and clinical
      signs such as a severe decrease in visual acuity, central or centrocecal scotomas
      in the perimetry and pseudoedema of the optic disc, followed by optic atrophy.
      Pathognomonic clinical signs of LHON are twisted vessels and ectatic capillaries
      in the fundus of these patients and their relatives of the maternal line, i.e.,
      peripapillary microangiopathy. A careful analysis of the patients' pedigrees,
      anamnesis and the functional and morphological results of the clinical
      examinations helps to avoid misdiagnosis of the disease. However, the expensive
      and time-consuming molecular genetic analysis is always necessary to confirm or
      exclude the diagnosis of LHON.

PMID- 9782730
TI  - [High resolution functional magnetic resonance tomography with Gd-DTPA eyedrops
      in diagnosis of lacrimal apparatus diseases].
AB  - Both dacryocystography and dacryoscintigraphy are well established in the
      evaluation of stenoses of the lacrimal drainage system. They provide limited
      information about the ductal anatomy itself and about periductal structures. MR
      imaging was evaluated for its capability to directly visualize the lacrimal
      drainage system in detail and simultaneously provide functional characterization
      of dacryostenosis. SUBJECTS AND METHODS: Twenty-seven lacrimal drainage systems
      of 23 patients suffering from epiphora were examined in an MR unit before and
      after conjunctival and intravenous application of Gd-DTPA using a surface coil.
      RESULTS: Dacryostenosis was found in 23 of 27 lacrimal systems. Stenoses were
      localized to the canalicular (n = 3), saccular (n = 8), and ductal (n = 12)
      level, and were classified as stenosis or occlusion. CONCLUSION: MR imaging with
      conjunctival contrast application allows within one examination both detailed
      morphological and functional assessment of the lacrimal drainage system with
      depiction of surrounding structures. Limitations arise mainly from demands on
      technical and patient-related preconditions.

PMID- 9782732
TI  - [Night driving capacity of ophthalmologically healthy persons of various ages].
AB  - In 1970 Aulhorn and Harms made fundamental recommendations for the night driving
      ability of motorists as well as for the corresponding examination methods.
      Reduced night driving ability of persons over the age of 60, as well the
      established limits for twilight vision and glare sensitivity, and their relevance
      to night-time collisions has been re-examined. PATIENTS AND METHODS: A total of
      117 normal volunteers between 10 and 79 years of age underwent ophthalmological
      examinations including measurement of contrast acuity and glare sensitivity by
      means of the Mesotest II (Oculus, Germany). RESULTS: Contrast acuity and glare
      sensitivity deteriorate in an age-dependent fashion. Thus, night driving ability
      decreased with increasing age. The majority part of persons over the age of 60
      were not able to fulfill the actual criteria for night driving ability according
      to the recommendations of the German Ophthalmological Society (DOG). CONCLUSIONS:
      In the present population, nearly 40% of persons over the age of 60 have reduced
      night driving ability. Since Lachenmayr showed in the BAST study the correlation
      of reduced night driving ability and car accidents, this emphasizes the
      importance of ophthalmological check-ups for motorists at this age.

PMID- 9782733
TI  - [Standardized evaluation of red, green and blue perception. Comparison between
      color arrangement and computer-assisted test procedures].
AB  - BACKGROUND: Computerized colortests offer the possibility of determining
      quantitative color contrast thresholds under standardized conditions. Arrangement
      tests allow semi-quantitative evaluation of the red, green and blue color sense.
      To validate the results of a new computerized test, its results are compared to
      those of arrangement tests. PATIENTS AND METHODS: Thirty-five patients with
      retinitis pigmentosa (RP, mean age 38.51, +/- 15.14) as well as 30 normal
      observers (mean age 36.52, +/- 14.33) were evaluated. The computerized color test
      COLDEF was used, which is a calibrated screen that presents color optotypes on a
      colored background. All colors are chosen from three-color confusion axes of the
      CIE-Lu'v' color chart (protan, deutan and tritan axis). By a staircase procedure,
      the colors of the optotype and background were varied until the observers minimal
      color contrast threshold is detected. To compare the results of COLDEF with a
      routine diagnostic tool, the Farnsworth panel D-15 and Lanthony desature test
      were chosen. The results of the arrangement tests were scored by a categorization
      scheme. RESULTS: Normal observers showed no elevated thresholds either in COLDEF
      nor in the panel tests. In the RP group increased thresholds along the blue
      confusion axis could be detected in most cases. Furthermore, COLDEF showed
      increased thresholds along the red and green axes in some patients. With the
      computerized test it is always possible to identify the color axis concerned. The
      new test allows a fast and quantitative assessment of acquired color vision
      deficiencies.

PMID- 9782734
TI  - [Sclera fixation of posterior chamber lenses in vitrectomized eyes.
      Perfluorocarbon as an operative aid].
AB  - INTRODUCTION: Accurate positioning of transsclerally fixated intraocular lenses
      in vitrectomized eyes is difficult to achieve because of the lack of stability of
      the globe. External stabilization with a Flieringa device is widely used.
      Internal stabilization, however, with liquid perfluorocarbon seems to be more
      advantageous. METHODS: Endostabilization with perfluorocarbon after pars plana
      vitrectomy prior to transscleral fixation of a posterior chamber lens was
      performed in 18 eyes. The intraocular lens floats on the surface of the
      perfluorocarbon. The level of the liquid can be adjusted to position the lens
      accurately. Transscleral fixation of the intraocular lens was followed by
      silicone oil injection in 4 eyes and by BSS injection in 14 eyes. RESULTS AND
      CONCLUSIONS: Endostabilization of the globe with liquid perfluorocarbon serves as
      a diaphragm preventing hemorrhage into the vitreous cavity and sliding of the
      intraocular lens, thus permitting proper positioning. There were no complications
      either intraoperatively, or postoperatively. Perfluorocarbon is a considerable
      aid in facilitating the positioning of a transsclerally fixated intraocular lens.

PMID- 9782735
TI  - [Systemic lysis therapy in retinal vascular occlusions].
AB  - In the management of acute major vessel occlusion, the use of fibrinolytic agents
      such as recombinant tissue plasminogen activator (rt-PA), urokinase or
      streptokinase is widely accepted. Today, the spectrum of indications for
      thrombolytic drugs comprises acute myocardial infarction, lung embolism,
      ischaemic stroke, deep vein thrombosis and acute arterial occlusions of the lower
      limbs. In view of the histopathological and clinical features of retinal vessel
      occlusion, fibrinolysis aimed at early restoration of blood flow appears to be a
      promising therapeutic approach. Basically, it is of some concern that the
      systemic administration of fibrinolytic agents is associated with a haemorrhagic
      risk. Since this includes cerebral haemorrhage or gastrointestinal bleeding, the
      choice of an appropriate intravenous thrombolytic therapy in a non-life
      threatening situation such as central retinal artery occlusion (CRAO) or central
      retinal vein occlusion (CRVO) should be based on minimising the risk of adverse
      events. Furthermore, the fibrinolytic treatment of choice should be able to
      produce rapid and complete restoration of retinal capillary and arterial or
      venous blood flow and maintain patency long enough for retinal salvage to take
      place. In this article, we review several studies of fibrinolytic therapy in
      patients with retinal vessel occlusion to determine whether this treatment is
      likely to improve major clinical outcomes. Moreover, we review the large scale
      trials of fibrinolysis in myocardial infarction and acute ischaemic stroke to
      evaluate safety and efficacy of various thrombolytic regimens. Furthermore, we
      report on our results of fibrinolytic therapy with low dose rt-PA in patients
      with retinal artery occlusion and ischaemic central retinal vein occlusion. In
      light of the fact that the occurrence of bleeding complications constitutes a
      dose dependent problem, we conclude that the use of low dose regimens should be
      the ideal approach to fibrinolysis in retinal vessel occlusion. Although the
      results of our pilot studies must be interpreted with caution, we believe that
      the administration of low-dose rt-PA (50 mg) in a frontloaded manner (=
      simultaneous administration of rt-PA and intravenous heparin) constitutes a
      reasonable treatment option in patients with central retinal artery occlusion
      (CRAO) or ischaemic retinal vein occlusion (RVO), recent onset of symptoms (CRAO
      < or = 12 h, RVO < or = 11 d) and severe visual loss (< or = 20/50). Because of
      these limitations and the numerous contraindications of fibrinolytic therapy,
      only a limited number of patients will be suitable for this treatment. In view of
      the poor visual and ocular prognosis in severe retinal vessel occlusion,
      controlled clinical trials are needed to determine the benefit of thrombolysis in
      the management of this disease.

PMID- 9782736
TI  - [Whitish crystalloid corneal deposits. Infectious crystalline keratopathy in
      amoebic keratitis].

PMID- 9782737
TI  - [Changes in saccades in endocrine orbitopathy. Clarification of the contribution
      by H. D. Schworm et al. "Functional eye muscle changes in endocrine
      orbitopathy"].

PMID- 9782738
TI  - [Fluorescein angiography in age-related macular degeneration].

PMID- 9782739
TI  - [Antibiotic therapy in leukopenia].
AB  - Intensified chemotherapy-induced long-term neutropenia is the main cause for
      morbidity and mortality of patients with hematologic malignancies. The successful
      management of neutropenia is based on hygienic procedures antimicrobial
      prophylaxis and therapy, and diagnostics. Until today, Co-Trimoxazole or
      fluoroquinolenes and oral amphotericine B are the prophylactic standard. The
      initial therapy of febrile neutropenia has to be started empirically before
      identification of causative pathogens or infectious foci. The febrile episodes
      should be treated with broad spectrum antibiotics (combinations or monotherapy)
      due to the spectrum of microorganisms or resistance situation at hospital. In
      case of non-response after 3-4 days the initial therapy should be modified, in
      addition to further antibacterial therapy the start with an antifungal drug has
      to be recommended. In patients with pulmonary infiltrates the early treatment
      with amphotericine B has been shown to be more advantageous than delayed
      antifungal therapy. Furthermore, the antibiotic therapy is based on proven
      microorganisms, susceptibility testing and infectious foci. The value of
      interventional treatment with G-CSF or GM-CSF is controversely discussed. An
      uncompromising handling of febrile neutropenia is necessary to reduce the
      mortality due to infections in patients with hematologic malignancies.

PMID- 9782740
TI  - [Staged analgesic therapy in tumor pain].
AB  - Overall, pain is one of the most common symptoms associated with cancer and often
      produces greater anticipatory distress than other features of the disease. Drug
      selection depends on the intensity of pain rather than on the specific
      pathophysiology. Mild to moderate pain can often be treated effectively by so
      called "weak" opioids. Non-opioid analgesics, like acetyl-salicylic acid or
      paracetamol can be added according to the "analgesic ladder" proposed by the
      World Health Organization (WHO). Opioids should be given on a fixed time schedule
      thereby, preventing pain from recurring. Additional rescue doses (approximately
      50 degrees, of baseline single dose) are given for breakthrough pain. Noninvasive
      (oral, rectal, sublingual, transdermal and intranasal) routes of application
      should be maintained as long as possible to preserve independence and mobility.
      When treatment by infusion therapy (subcutaneous, intravenous, epidural) has been
      elected, the addition of patient controlled analgesia (PCA), which permits
      patients to administer a preset amount of narcotic at preset intervals, is an
      effective means to manage breakthrough and incident pain in selected patients.
      Antidepressants, anticonvulsants and some antiarrhytmics are used as co
      analgesics. Oral medication alone can guarantee pain relief in about 95% of the
      patients. The WHO analgesic ladder has proven effective in all settings of
      patients care.

PMID- 9782741
TI  - [Implantable catheter systems].
AB  - Central venous access devices represent a definitive improvement in childhood
      cancer therapy. The silicone elastomer catheters offer a both save and easy
      access, low related morbidity and acceptance by patient. Tunnelled right atrial
      catheter (Broviac, Hickman-Crawford or Quinton) for long-term use are firstline
      choice for venous access. Although ports reduce the number of complications and
      manipulations associated with percutaneous catheters, they are not devoid of
      problems. Related complications are catheter infection and occlusion or damage.
      The different techniques of venous vascular access and management of
      complications are reported.

PMID- 9782742
TI  - [Anticipatory nausea and anticipatory vomiting, food aversion and anticipatory
      immunomodulation: classical conditioning in cytostatic drug treatment of
      pediatric chemotherapy patients].
AB  - Nausea and/or vomiting are adverse side-effects of cancer chemotherapeutic drugs
      in adult as well as pediatric cancer patients' complicating treatment and
      compliance. Nausea and vomiting are not only experienced as posttreatment
      symptoms after chemotherapy (i.e., posttreatment nausea and/or vomiting). In a
      subgroup of cancer patients, these symptoms also occur prior to a
      chemotherapeutic drug infusion, called anticipatory nausea (AN) and anticipatory
      vomiting (AV). The aim of this paper is to present a model derived from basic
      psychology to explain anticipatory symptoms as learned responses based on
      classical conditioning. In addition, food aversions and also immunomodulation are
      interpreted as conditioned responses. Some data on prevalence of ANV in a
      pediatric sample and on the correspondence between anticipatory symptoms and
      predictions from the conditioning model are presented. Finally, therapeutic
      techniques to prevent AN and/or AV are deduced from the conditioning model.

PMID- 9782743
TI  - [Treatment with blood components and coagulation factor concentrates--modern
      concepts of hemotherapy].
AB  - Transfusion of whole blood is the most common and successful organ
      transplantation world wide. It is in use longer than any other transplantation
      procedure. With the exception of uses in situations of crisis, treatment with
      whole blood is nowadays obsolete. This is due to enormous progress in preparation
      technologies. As a result blood from volunteer donors is separated before
      therapeutic use into its cellular and plasmatic components. The latter may be
      further processed into subfractions or secondary products. The advantages of this
      strategy are evident: a) the crude pharmaceutic material blood is used optimally,
      b) the isolated components may be stored over periods appropriate for their
      stability be it in a cryopreserved state or after biochemical, immunologic or
      biological modification, c) the patient receives only the blood components he
      needs, d) the transfusion of unnecessary fractions of blood is avoided, e) the
      rate of transfusion-associated adverse events is reduced, f) the physician has a
      basis for customized hematotherapy. Important implications concern logistics,
      economy, differentiated therapy and drug safety consideration. This contribution
      gives an overview on progress made in therapy of hematologic and oncologic
      patients with blood products and concentrates of coagulation factors. It
      demonstrates selected aspects of actual interest for optimal hemotherapy.

PMID- 9782744
TI  - [Growth factors in oncology: effectiveness and prospects].
AB  - The hematopoietic growth factors G-CSF and GM-CSF stimulate the proliferation and
      differentiation of myeloid precursor cells leading to an accelerated granulocytic
      regeneration after chemotherapy and to a shortened duration of "febrile
      neutropenia". Criteria for the clinical application should be defined which take
      the advantage for the comfort of the patient and the economic aspect into
      account. The American Society for Clinical Oncology has published recommendations
      for the treatment with hematopoietic colony-stimulating factors, which are useful
      with the exception of the proposal to reduce the chemotherapy dose with the goal
      to save expensive CSF treatment. The use of CSF for treatment of afebrile and
      uncomplicated neutropenia should be reduced.

PMID- 9782745
TI  - [Therapy of recurrent hepatitis C after liver transplantation].

PMID- 9782746
TI  - [Prevention of multiple pregnancies after ovulation induction with
      gonadotropins].

PMID- 9782747
TI  - [Bone ultrasound and diagnosis of osteoporosis: correlation of 2 quantitative
      ultrasound methods with bone density].
AB  - In this study, 96 women (mean +/- SD, 65.3 +/- 13.2 years) were investigated by
      bone mineral densitometry (DXA, Hologic QDR 2000) and quantitative ultrasound
      (QUS) of the tibia (n = 96; Sound-Scan2000, Myriad) and phalanges (n = 84: DBM
      Sonic 1200, IGEA). We observed a good correlation of QUS measurement with bone
      mineral content (BMD) on lumbar spine and both hips (Ward and Neck). Correlation
      of the two QUS-techniques measuring at different skeletal sites within the same
      patient was good. QUS instruments measuring at the various skeletal sites and
      their suitability for screening patients at risk of osteoporosis are discussed.
      The usefulness of the different QUS methods and the best measuring site for the
      assessment of fracture risk in osteoporotic patients still have to be
      established.

PMID- 9782748
TI  - [Critical evaluation of a publication on a diagnostic test ].

PMID- 9782749
TI  - [Cogan syndrome--a case report].
AB  - We present a case report of Cogan's syndrome and a review of the literature.
      Cogan's syndrome, described in 1945, consists of nonsyphilitic interstitial
      keratitis accompanied by rapidly progressive bilateral hearing loss, tinnitus,
      and vertigo. 40% develop bilateral complete deafness and 70% show signs of
      systemic disease mostly in the form of cardiovascular symptoms. The mortality
      rate of 10% is mainly due to vasculitis. The disease is caused by an autoimmune
      response. One male patient had a typical interstitial keratitis and bilateral
      dramatically progressive deafness combined with failure of the vestibule.
      Corticosteroids and immunosuppressants are the treatment of choice. The
      importance of being aware of audiotory-vestibular dysfunction occurring in
      patients with ocular inflammation and the role of early immunotherapy in
      preventing deafness has to be emphasised.

PMID- 9782751
TI  - [Acute cytomegalovirus infection].

PMID- 9782750
TI  - [Headache, general malaise and left-side ptosis].
AB  - A 82-year-old female was admitted to hospital because of deteriorated general
      condition, severe diffuse headache and complete left-sided ptosis. A computed
      tomography scan of the head revealed no subarachnoid haemorrhage. Based on the
      hypothesis that the symptoms resulted from an infarction in the brain stem, the
      previous medication with Aspirin was continued. After repeated vomitus
      hypotensive dehydration developed and was adequately treated. Because of
      confusion, elevated white blood counts and signs of meningism, a spinal puncture
      was performed. Only the serology for Borrelia-IgG was positive, therefore the
      patient received Rocephin. During treatment only the ptosis persisted, therefore
      the substitution with sodium and the medication with Prednisone were stopped.
      Afterwards the symptoms reappeared and the laboratory results showed
      insufficiency of the pituitary. A magnetic resonance scan showed a microadenoma
      of the pituitary with local bleeding. Nine months after pituitary apoplexy, with
      hormonal substitution only a divergent strabism on the left side persisted.
      Clinical findings, course and therapy of pituitary apoplexy are discussed.

PMID- 9782752
TI  - [Neonatal screening for hereditary diseases].

PMID- 9782753
TI  - [Electrosurgical loop procedures in ambulatory gynecology].
AB  - The article gives a survey of the new electrosurgical excision procedures that
      are gaining widespread use in office gynaecology in the nineties. A special
      emphasis is put on the easy learning procedures, relatively low cost of equipment
      and the results, which seem to match the results of cold-knife- and laser
      conization. The advantages and pitfalls of the see-and-treat principle are
      discussed and the indications, other than cervical intraepithelial neoplasia, are
      mentioned.

PMID- 9782754
TI  - [Combination therapy of rheumatoid arthritis].
AB  - The prevalence of rheumatoid arthritis (RA) is about 0.5-1%. The disease course
      is variable, but RA causes substantial morbidity and mortality. The effect of
      conventional therapy for RA, i.e. nonsteroidal antiinflammatory drugs (NSAID),
      glucocorticosteroids and Slow Acting Anti-Rheumatic Drugs (SAARD) including
      methotrexate, gold salts, anti-malarials, d-penicillamine and salazopyrine, is
      often suboptimal. Since the aim of treatment is a complete remission, combination
      therapy, i.e. treatment with two or more SAARDs, may be feasible since an
      additive/synergistic effect may be obtained. In this paper the literature about
      the effectiveness and toxicity of combination therapy is reviewed. Only a few
      randomized, clinically controlled trials have been published. None of them have
      documented that gold salts, d-penicillamine and azathioprine in combination with
      other SAARDs are better than monotherapy. However, recent trials have indicated
      that methotrexate in combination with salazopyrine and hydroxychloroquine or in
      combination with cyclosporine may cause a better therapeutic effect than
      methotrexate alone, without additional toxicity. Long term studies of the effect
      of combination therapy are not yet available.

PMID- 9782755
TI  - [Neonatal screening in Denmark. Status and future perspectives].
AB  - In Denmark, the Faroe Islands, and Greenland, comprehensive screening of newborns
      for phenylketonuria and congenital hypothyroidism has been carried out for 20
      years. The screening programme has detected 98 and 356 patients, respectively,
      corresponding to incidences of 1:12,000 and 1:3,400. The future savings on health
      care expenditures resulting from one year of neonatal screening are estimated to
      be 196 million DKK in present day value, which is 28 times higher than the cost
      of screening. The screening samples are stored in a biobank, which is used in
      diagnosis of congenital diseases and infant deaths and for development of future
      screening methods. It is desirable to expand the existing screening programme to
      include a range of rare inherited metabolic diseases, which collectively are
      frequent. This is realistic with the advent of tandem mass spectrometry, which
      allows cost-effective simultaneous screening for a group of inborn errors of
      metabolism.

PMID- 9782756
TI  - [Loop conization of cervix uteri in gynecological practice].
AB  - Loop electrosurgical excision procedures (LEEP) in Danish office gynaecology was
      introduced in April 1992. This paper gives a retrospective survey of 1388 LEEP
      performed on 1347 patients out of an estimated number of 1483 LEEP on a
      nationwide basis in private gynaecological practice until the end of March 1996.
      At the end of the study period 46% of full-time-practices performed the
      operation. Indications were almost exclusively CIN. The complication rate was
      10.5% in this introductory period, mainly as relatively modest postoperative
      bleeding. Almost all patients were preoperatively assessed by cervical biopsies
      and/or endocervical curettage, and information on preoperative colposcopy was
      obtained in 96.2% of the procedures. Unsuspected invasion was found in 2.3%. Cure
      rate/LEEP was 92.5% at four-month follow-up and 89.4% at 16-month follow-up. We
      conclude that the method, even in the introductory period of an office setting,
      has acceptable complication and cure rates. Postoperative follow-up, however, is
      mandatory.

PMID- 9782757
TI  - [Prolonged pregnancy. Labor induction versus intensified monitoring].
AB  - This study was made in order to evaluate the effect of a policy of induction of
      labour at 42 weeks of gestation in post-term pregnancies. A group of 139 women
      with uncomplicated post-term pregnancies, who gave birth at the maternity ward at
      Herlev Hospital in 1993 was compared to a group of 145 women, who gave birth in
      1996 at the same location. In 1993 spontaneous labour was awaited with twice
      weekly surveillance tests, and labour was only induced if there was evidence of
      foetal or maternal compromise, while in 1996 labour was induced at 42 weeks of
      gestation. There were at 20.1% inductions of labour in 1993 compared to 44.8% in
      1996. The perinatal morbidity and birth complication rates were similar in the
      two groups.

PMID- 9782758
TI  - [Hand symptoms and pregnancy].
AB  - The purpose of the present study was to identify the incidence of hand symptoms
      related to pregnancy in a Danish population. Three hundred and thirty-five
      consecutive postpartum patients were interviewed by questionnaire. Hand symptoms
      had been noted by 16%, among these 30% described a classic median-nerve symptom
      distribution (carpal tunnel syndrome) and 24% of patients described an ulnar
      nerve distribution. Most symptoms were bilateral, commenced in the third
      trimester and resolved soon after delivery. There was a significant correlation
      of hand symptoms in pregnancy with the presence of swelling and a significant
      correlation to parity (first). Hand function and sleep had been disturbed in half
      of the patients. Half of the patients had mentioned their symptoms to their
      doctor and one had been sent to treatment. Hand symptoms during pregnancy are
      common, and their severity is often underestimated. Symptoms of the carpal tunnel
      syndrome are easily relieved by a night splint.

PMID- 9782759
TI  - [Multiple pregnancies in Denmark 1980-1994].
AB  - The objective was to study trends in national rates of multiple pregnancies that
      were not explained by changes in maternal age and parity. Information on
      childbirths to Danish-born women were obtained from national registers. The
      national incidence of multiple pregnancies increased 1.7-fold during 1980-1994,
      the increase primarily in 1989-1994 and almost exclusively in primiparous women >
      or = 30 years, for whom the adjusted population-based twinning rate increased 2.7
      fold and the triplet rate 9.1-fold. The proportion of multiple births among
      infant deaths in primiparous women > or = 30 years increased from 11.5% to 26.9%.
      In conclusion, the marked increase in the rate of multiple pregnancies, which in
      particular was observed during the 1990s and in primiparous women > or = 30
      years, could not be explained by changes in maternal age or parity. Fertility
      enhancing treatments are believed to have caused this increase.

PMID- 9782760
TI  - [Follow-up of non-negative cervical cytological smears in the county of Funen].
AB  - The outcome of screening for cervical cancer in the county of Funen was evaluated
      in two sequential periods (1.7.-31.12.1989 and 1.7.-31.12.1992), comprising
      17,493 and 18,135 respectively. About 10.5% of the screened women had a define
      non-negative smear. From the first and the second period 80% and 85.1% of the non
      negative smears respectively were followed up within six months. The follow-up of
      positive smears was 96% in both periods. Four point nine percent and 3.3%
      respectively of the non-negative smears were not followed up within 18 months. No
      women were actually lost in the screening system, unless they renounced further
      follow-up themselves. The follow-up was improved from the first to the second
      period, presumably as a result of a better general acquaintance with the
      screening procedures. The study indicates that reorganization of a screening
      programme requires both time and adjustment. Moreover, it is important that a
      successful screening programme frequently adjusts its procedures.

PMID- 9782761
TI  - [Evaluation of PAPNET--a semiautomated system used in the screening against
      cervical cancer].
AB  - The PAPNET-system is a current example of automated technological progress in the
      pathological laboratory field. As the first Department of Pathology in Denmark,
      we have tested the applicability of this semi-automatical screening system in
      screening against cervical cancer. 3000 prospectively selected cervical smears
      were entered into the project. 1500 of these were first prescreened by the use of
      PAPNET and the negative slides were then manually rescreened. The remaining 1500
      slides consisted of manually screened smears diagnosed as negative or inadequate.
      They were subsequently rescreened by the use of PAPNET. We only found one false
      negative smear in each group. Compared with histological follow-up the diagnoses
      CIN 1-3 were histologically confirmed in both groups. The PAPNET-assisted
      screening of cervical smears is faster, more valid and less fatiguing than the
      conventional screening method. Nevertheless, our results show no diagnostic
      quality improvement by the use of PAPNET. This is probably due to a strict
      screening procedure and a limited work load of a maximum of about 40-50 slides
      per cytotechnologist a day in our laboratory.

PMID- 9782762
TI  - [Therapeutic angiogenesis. A new therapeutical principle in tissue ischemia].

PMID- 9782763
TI  - [Injuries of the cervical spine in children].

PMID- 9782764
TI  - [Injuries of the cervical spine in children].
AB  - Injuries of the spine in children rarely occur. They amount to about 0.2% of all
      fractures and dislocation and to 1.5 to 3% of all lesions of the spine. The
      younger an injured child is, the more likely it has sustained a lesion of the
      upper cervical spine. This spinal segment in comparison to adults is concerned
      more often and accounts for 50% of all C-spine injuries. Important differences
      between the adult spine and the spine in the child disappear with the age of 10
      years. Later diagnostics, classification and treatment correspond widely with the
      principles valid in adults. The knowledge of the normal shape and development of
      the spine are crucial in avoiding misinterpretations of X-ray films. Typical
      examples include the confusion of synchondrosis with fractures or of subluxations
      of the atlas and the C2/C3 segment with "true" instabilities. Relevant lesions
      always are accompanied by clear clinical symptoms. Specific injuries of the
      growing axial skeleton are lesions of the cartilaginous endplates and "fractures"
      of the synchondrosis. Atlantooccipital dislocations (AOD) occur typically in
      children. According to our experiences with 16 AOD we propose--dependent on the
      direction of dislocation of the occipital condyles--a simplified classification
      in anterior, posterior and completely unstable AOD. In one boy in our series we
      treated the lesion successfully by temporary internal fixation. He presented a
      massive improvement of initially subtotal neurologic symptoms. Injuries to the
      synchondrosis of the dens represent another typical lesion in childhood. Four out
      of 5 children treated in our clinic were involved as back seat passengers in head
      on motor vehicle accidents. Three of them were restrained by 4 point children's
      seat harnesses. For conservative treatment we prefer a halo and plaster-vest for
      12 weeks after closed reduction. We recommend operative treatment in cases of
      major dislocation with greater instability where it may be impossible to maintain
      alignment with halo fixation. Surgical equipment and techniques correspond in
      detail to those used in adults. Three of the five children mentioned have been
      stabilized successfully by anterior screw fixation. Atlantoaxial dislocations
      (AAD) are divided into translatory and rotatory instabilities. Sagittal
      dislocations of the atlas in children also need to be fixed by a fusion between
      C1 and C2. Rotatory instabilities in the acute phase are easy to reduce and are
      treated with a halo-fixator. According to our experiences in two delayed cases
      anatomical reduction is also possible after months partly by open, partly by
      closed means. For the lower C-spine lesion with encroachment of the spinal canal
      and above all ligamentous injuries represent a clear indication for operative
      treatment because, similar to the adult spine, they do not become stable after
      close management.

PMID- 9782765
TI  - [Clinical and nuclear magnetic resonance tomography diagnosis of glenoid labrum
      injuries].
AB  - PURPOSE: Clinical and radiological evaluation of labral tears remains
      challenging. It has been shown that intravenous administration of contrast agents
      produces an MR arthrographic effect without the need for intraarticular
      injection. This is the first study evaluating this new technique of indirect MR
      arthrography in diagnosis of glenoid labrum tears. METHODS: 28 patients with
      clinically suspected labral injuries were prospectively investigated (1.5 Tesla,
      flexible surface coil). A native MR exam of the shoulder (transverse and oblique
      coronar orientation, T1-weighted spin-, proton density- and T2*-weighted gradient
      echo sequences) and indirect MR arthrography (transverse and oblique-coronar
      orientation, fat-suppressed T1-weighted spin-echo sequences, intravenous
      injection of gadopentetate dimeglumine [0.1 mmol/kg], followed by 10-15 min of
      joint movement) were performed. Results were confirmed by arthroscopy and/or open
      surgery. Additionally sensitivity evaluation of clinical tests for investigation
      of labral tears were performed. RESULTS: Indirect MR-Arthrography improved
      delineation of the glenoid labrum and hyaline cartilage significantly (p < 0.05).
      Sensitivity and specificity of indirect MR arthrography in diagnosis of labral
      injuries were 90% and 89% respectively, compared to 79% and 67% of the native MR
      exam. The reliability of the checked clinical tests is not sufficient enough to
      determine labral lesions (predictive value between 50 and 70%). CONCLUSION:
      Indirect MR-arthrography is a promising non-invasive technique in the evaluation
      of the glenoid labrum.

PMID- 9782766
TI  - [Endoscopically controlled division of the diaphragm. A minimally invasive
      approach to ventral management of thoracolumbar fractures of the spine].
AB  - On 90 patients with 93 unstable fractures of the thoracic spine and the
      thoracolumbar junction we treated by a minimal invasive procedure between may
      1996 and april 1998, in 46 patients an endoscopic splitting of the diaphragm was
      performed. The diaphragma was dissected at its attachment at the spine and the
      adjoining costal base. After partial corporectomy and discectomy, a tricortical
      bone graft has been inserted. An additional stabilization was done by using a
      plate and screw system. The incision of the diaphragm was closed by suturing or
      using an universal endostapler. Controlling the postoperative results a complete
      closure of the incision was documented by X-ray and CT-scan. There was no
      conversion to the open procedure or postoperative infection. Splitting the
      diaphragma opens also the thoracolumbar junction to a minimal invasive treatment
      and stabilization of fractures.

PMID- 9782767
TI  - [Intramedullary boring in infected intramedullary nail osteosyntheses of the
      tibia and femur].
AB  - The infection after intramedullary nailing is a severe complication, which is
      hard to eradicate. The results of reaming the intramedullary canal after removal
      of the infected nail were evaluated in our investigation. From 1984 to 1991 fifty
      five patients with infected intramedullary nails of the lower extremity were
      included in this trial. Twenty-one patients had an infection of the femur. Thirty
      four patients had a primary infection of the nail, twenty-one patients had
      multiple operations with periods of infection prior to nailing. All patients had
      signs of a chronic osteitis and sinus formation. At the time of the follow-up the
      success of the procedure was evaluated regarding recurrence of infection, range
      of motion of the extremity and patient comfort. The mean time of observation was
      10.1 +/- 4.9 years. All patients with initially infected intramedullary nails had
      no recurrence of the infection, compared to 62% of those with multiple operations
      prior to nailing. At the time of the follow up all fractures had healed. 85% of
      the patients performed full weight bearing. 32 patients (91%) had good or
      excellent ROM of the adjacent joints. CONCLUSION: Intramedullary reaming after
      infected nails is a successful procedure and results in infect healing in the
      majority of patients.

PMID- 9782768
TI  - [Femoral neck fractures--diagnosis and therapeutic procedure].

PMID- 9782769
TI  - [Vacuum sealing as carrier system for controlled local drug administration in
      wound infection].
AB  - Between 1.4.96 and 1.3.97 27 patients with acute infections of bone and soft
      tissues (n = 13), chronic osteomyelitis (n = 8), and chronic wounds (n = 6) were
      treated by using Instillation-Vacuum-Sealing. Polyvinylalcohol sponges with
      drainage tubes were used to cover the internal or external wound surfaces which
      resulted from surgical debridement. Having hermetically covered the wound with a
      transparent film dressing a vacuum source generated a partial vacuum in the
      sponge which was modified according to the type of wound between 20 and 80 kPa.
      Several times daily, the vacuum line was blocked and, in an alternating fashion,
      antiseptic or antibiotic solution instilled for 30 minutes. Then, the vacuum was
      reestablished and the fluids drained from the wound. Seven days later,
      intermittent drug instillation was stopped and there was either immediate or
      delayed wound closure by secondary suturing (n = 22), skin grafting (n = 3) or
      spontaneous epithelialization (n = 2). During a follow-up from the beginning of
      the instillation treatment of 4.2 (3-14) months there was one recurrency of
      infection in a patient with chronic osteomyelitis.

PMID- 9782770
TI  - [Subdural abscess as a complication of halo fixator].
AB  - Complications associated with the application of a halo device are not
      infrequent; however, osteomyelitis of the skull with a consecutive subdural
      abscess is a rare but severe complication. We present the case of a patient with
      a subdural abscess as a result of a local pin-track infection of the halo device,
      in whom pathological behavior was the primary clinical finding. The possible
      complications associated with the halo device are discussed with emphasis on
      associated head injuries and preexisting neurological diseases, as well as
      indications for the halo, clinical symptoms of pin-track infections, necessary
      diagnostic measurements and the appropriate treatment.

PMID- 9782771
TI  - [Recurrent soft tissue infections after accidental inoculation with BCG vaccine].
AB  - Complications after BCG vaccine (bacilli Calmette-Guerin) occur rarely. They can
      reach from a local acute abscess to chronic ulceration's. Therapeutically
      concepts of these complications range from conservative to operative treatment.
      In the following case history recurrent soft tissue infections occurred after
      accidental inoculation with BCG vaccine. The time course of these recurrent
      infections with its therapeutic options is discussed and a treatment strategy is
      suggested. Currently, radical excision combined with antituberculotic treatment
      seems to be the most promising therapy of this specific soft tissue infection.

PMID- 9782772
TI  - Progress towards poliomyelitis eradication, India, 1998.

PMID- 9782773
TI  - The Children's Vaccine Initiative (CVI) and WHO's global programme for vaccines
      and immunization (GPV). Recommendations from the scientific advisory group of
      experts (SAGE).

PMID- 9782774
TI  - Progress in the design of DNA sequence-specific lexitropsins.
AB  - Sequence-specific polyamides that bind in the minor groove of DNA are attractive
      candidates for antibiotics, cancer chemotherapeutics, and transcriptional
      antagonists. This paper reviews the progress of structure-based design of minor
      groove-binding polyamides, from the first structure of netropsin with DNA, to the
      effective linked polyamides currently under study. A theory of polyamide
      specificity is also reviewed, introducing methods to determine the optimal
      strategies for targeting a given DNA sequence within a genome of competing
      sequences.

PMID- 9782775
TI  - DNA recognition by beta-sheets.
AB  - The modes of DNA recognition by beta-sheets are analyzed by using the known
      crystal and solution three-dimensional structures of DNA-protein complexes. Close
      fitting of the protein surface and the DNA surface determines the binding
      geometry. Interaction takes place so that essentially the N-to-C direction of the
      beta-strands either follows or crosses the DNA groove. Upon following the major
      groove a two-stranded antiparallel beta-sheet dives into the groove and contacts
      DNA bases with its convex side facing the DNA, while upon following the minor
      groove, it binds around the sugar-phosphate backbones, with its opposite concave
      side shielding the DNA. In order for the beta-strands crossing the minor groove
      to interact with the DNA, the dinucleotide steps need to almost totally helically
      untwist and roll around major groove. The beta-sheet, on the other hand, needs to
      adopt a concave curvature on the binding surface in the direction that follows
      the DNA minor groove, and a convex surface in the direction that bridges the
      sugar-phosphate backbones across the groove. The result is to produce a
      hyperbolic paraboloidal DNA-binding surface.

PMID- 9782776
TI  - Helix bending as a factor in protein/DNA recognition.
AB  - Normal vectors perpendicular to individual base pairs are a powerful tool for
      studying the bending behavior of B-DNA, both in the form of normal vector plots
      and in matrices that list angles between vectors for all possible base pair
      combinations. A new analysis program, FREEHELIX, has been written for this
      purpose, and applied to 86 examples of sequence-specific protein/DNA complexes
      whose coordinates are on deposit in the Nucleic Acid Data Base. Bends in this
      sample of 86 structures almost invariably follow from roll angles between
      adjacent base pairs; tilt makes no net contribution. Roll in a direction
      compressing the broad major groove is much more common than that which compresses
      the minor groove. Three distinct types of B-DNA bending are observed, each with a
      different molecular origin: (1) Localized kinking is produced by large roll at
      single steps or at two steps separated by one turn of helix. (2) Smooth, planar
      curvature is produced by positive and negative roll angles spaced a half-turn
      apart, with random side-to-side zigzag roll at intermediate points, rather than a
      tilt contribution that might have been expected theoretically. (3) Three
      dimensional writhe results from significant roll angles at a continuous series of
      steps. Writhe need not change the overall direction of helix axis, if it is
      continued indefinitely or for an integral number of helical turns. A-DNA itself
      can be formally considered as possessing uniform, continuous writhe that yields
      no net helix bending. Smooth curvature is the most intricate deformation of the
      three, and is least common. Writhe is the simplest deformation and is most
      common; indeed, a low level of continuous writhe is the normal condition of an
      otherwise unbent B-DNA helix of general sequence. With one exception, every
      example of major kinking in this sample of 86 structures involves a pyrimidine
      purine step: C-A/T-G, T-A, or C-G. Purine-purine steps, especially A-A, show the
      least tendency toward roll deformations.

PMID- 9782777
TI  - DNA recognition by structure-selective nucleases.
AB  - The nucleases discussed in this review show little sequence specificity but
      instead recognize certain structural features of their respective DNA substrates.
      The level of their structural selectivity ranges from simple discrimination
      between single- and double-stranded DNA (nucleases P1 and S1), the recognition of
      helical parameters like groove width and flexibility (DNase I), the recognition
      of helical distortions caused by abasic sites (exonuclease III, HAP1), to the
      recognition of specialized structures like flap DNA (5'-nucleases of eukaryotes,
      phages, and eubacterial DNA polymerases) and four-way junctions (T4 endonuclease
      VII, RuvC). The discussion is focused on the structural basis of the recognition
      process. In most cases the available x-ray structures of the nucleases and/or
      their DNA complexes have revealed the presence of structural motifs explaining
      the observed structural selectivity.

PMID- 9782778
TI  - DNA recognition and nucleosome organization.
AB  - The affinity of a DNA sequence for the histone octamer in a core nucleosome
      depends on the intrinsic flexibility of the DNA. This parameter can be affected
      both by the sequence-dependent conformational preferences of individual base
      steps and by the nature and location of the exocyclic groups of the DNA bases. By
      adopting highly preferred conformations particular types of base step can
      influence the rotational positioning of the DNA on the surface of the histone
      octamer. The asymmetry of the next higher order of chromatin structure is
      determined in part by the asymmetric binding of the globular domain of histone H5
      to the core nucleosome.

PMID- 9782779
TI  - Arginine vasopressin as a neurotransmitter in brain.
AB  - Arginine vasopressin (AVP) which exerts diverse biological effects in mammals is
      no more restricted to the posterior pituitary. Neurons containing AVP are seen in
      many other areas and in CNS vasopressinergic neurons are identified from the
      neocortex to the spinal cord. With the characterization of three different types
      of vasopressin receptor subtypes V1a, V1b and V2 responsible for its actions,
      their cloning and identification in different areas--especially in the brain many
      more hitherto unknown functions of AVP in brain has come to light. Added to this
      is the recently available specific vasopressin receptor antagonists. At present
      AVP seems to be involved in memory retrieval, learning, circadian time keeping,
      modulating the actions of area postrema and many other functions in brain. In the
      suprachiasmatic nuclei (SCN)--the biological clock--an area of the brain where
      the role of VP is still not very clear, VP is found to participate not only in
      transmitting the circadian rhythms to the rest of the brain but also serves the
      function of synchronizing and amplifying the pacemaker output of SCN. AVP can act
      not only as a neurotransmitter but also can stimulate the production of
      chemicals/neurotransmitters and thereby act as a mediator. It may be concluded
      that there is a central vasopressinergic system which participates in a variety
      of physiological and behavioral functions of brain.

PMID- 9782780
TI  - Effect of aspirin and sodium salicylate on cataract development in diabetic rats.
AB  - The role of acetylation in the antiglycating and anticataract effects of aspirin
      (ASA) is explored by comparing ASA's effects with that of sodium salicylate (SS),
      a nonacetyl analog of ASA, on cataract development in diabetic rats. Streptozocin
      diabetic rats were provided with either ASA or SS, orally, for 24 weeks.
      Appropriate drug controls, normal controls and diabetic controls were run in
      parallel. Periodic estimations of blood glucose, glycated hemoglobin and
      assessments of cataract progression were done. After 24 weeks lenses were
      removed, homogenised and separated into water soluble fraction and urea soluble
      fraction. The glycated lens proteins in each fraction was quantified. Results
      were analysed statistically and interpreted in relation to serum salicylate
      levels. Both ASA and SS did not influence blood glucose levels. In the untreated
      diabetic groups the onset and progression of cataract was quicker and complete
      within 16 weeks. Both ASA and SS delayed the onset and progression in diabetic
      rats, but ASA's effect was more pronounced than that of SS. The levels of
      glycated Hb and lens proteins in diabetic rats were significantly reduced by ASA
      and not by SS for the same serum salicylate levels. ASA's anticataract potential
      far exceeds that of SS and it is ASA, and not SS, that inhibits protein
      glycation. Thus the results favour the hypothesis that acetylation plays a major
      role in ASA's anticataract effect via inhibition of glycation.

PMID- 9782781
TI  - Anticonvulsant profile of Siotone granules, a herbal preparation.
AB  - Siotone granule, a herbal psychotropic formulation was tested for its
      effectiveness in various models of convulsions in animals. S. granule (100 and
      200 mg/kg) offered significant protection against pentylenetetrazol-, maximal
      electroshock- and strychnine-induced convulsions. In hypoxic stress-induced
      convulsions only 200 mg/kg was effective. It also reduced percent mortality per
      se and rendered total protection when given in combination with sub-protective
      dose of diazepam (0.5 mg/kg) and MK-801 (0.1 mg/kg) against pentylenetetrazol
      induced convulsions. The anticonvulsant action of S. granule was blocked by
      flumazenil (4 mg/kg) suggesting the involvement of GABAergic mechanism.

PMID- 9782782
TI  - Mechanism and specificity of immunoprotection induced by mycobacterial proteins
      against experimental tuberculosis in mice.
AB  - Mechanism of immunoprotection and specificity of two highly immunoprotective
      mycobacterial proteins, viz. 71 and 30 kDa were investigated. The adoptive
      transfer studies indicated that immunoprotection was mainly mediated by
      cooperative effect of CD4+ and CD8+ (66.7-73.3% on the basis of percent survival)
      which was further enhanced marginally by supplementation of B cells, natural
      killer cells, dendritic cells, macrophages and other immune cells. The
      specificity studies indicated that both the proteins did not cross react with the
      unrelated intracellular pathogens i.e. Aspergillus fumigatus, Salmonella typhi
      and Leishmania donovani as seen by T cell proliferation assay. The protection
      imparted by these mycobacterial proteins was also specific as the 71 and 30 kDa
      primed mice did not exhibit any cross protection against sublethal challenge of S
      typhi. The results indicate 71 and 30 kDa mycobacterial proteins to contain T
      cell specific epitopes responsible for specific immunoprotection, thus indicating
      their potential role as antituberculous vaccine candidates.

PMID- 9782783
TI  - Enhancement of thermal effect in virally infected mammalian cells in vitro and
      its modification by chlorpromazine.
AB  - NIH/3T3 cells chronically infected with Moloney murine leukemia virus (M-MuLV)
      were more thermosensitive than uninfected cells. Cells upregulated by a primary
      dose of heat formed giant colonies and had an altered response to a second dose
      of heat. Thermosensitivity depended upon the time elapsed between heat
      treatments. Heating the cells at either 42 degrees or 42.5 degrees C yielded
      biphasic survival curves, indicating a mixed population of productively infected
      and quiescent cells. Hyperthermia at 43 degrees C abolished this effect. Thermal
      sensitivity of infected cells was correlated with the expression of a viral
      reporter protein. Chlorpromazine (CPZ), a membrane active drug potentiated the
      heat effect in both uninfected and virally infected cells. The drug also
      abolished the biphasic effect of heat in infected cells, suggesting that heat
      sensitivity of both productively and quiescent cells is membrane mediated. The
      combined effect of heat at 42.5 degrees C and CPZ was equivalent to the effect of
      heat alone at 43.5 degrees C. These observations indicate that heat can
      selectively be lethal to productively infected cells and the membrane active
      drugs could further amplify this hyperthermic effect.

PMID- 9782785
TI  - Optimisation of different physical parameters for bioleaching of phosphate by
      Aspergillus niger from Indian rock phosphate.
AB  - A mutant strain of Aspergillus niger AB100 was incubated with samples of rock
      phosphate. Mutation resulted in a greater amount of solubilisation (30 to 35%) as
      against the parent strain (10 to 15%). The influence of leaching parameters such
      as ore concentration (pulp density), particle size, initial pH of the medium,
      temperature, volume of the medium in 250 ml flasks, inoculum concentration and
      age of inoculum was studied. When low quantity of rock phosphate is applied
      (0.1%) the solubilisation of phosphorus was optimal (40.5%). Optimum particle
      size was--200 to 240 mesh, initial pH of the medium 4.0, optimum volume of the
      fermentation medium 160 ml, time period of incubation was 8 days, inoculum volume
      was 7.5 ml, and age of inoculum 7 days. The maximum leaching of phosphorus by
      using these optimum physical parameters is 45 to 50%.

PMID- 9782784
TI  - Subchronic oral hepatotoxicity of turmeric in mice--histopathological and
      ultrastructural studies.
AB  - Dietary administration of the whole spice turmeric (0.2%, 1.0%, 5.0%) or
      ethanolic turmeric extract (ETE, 0.05%, 0.25%) for 14 days, at doses reported to
      be cancer preventive in model systems, were found to be hepatotoxic in mice.
      Histopathological evaluation showed coagulative necrosis accompanied by a zone of
      regenerating parenchymal cells of liver. The ultrastructural changes in liver
      parenchymal cells were non-specific reaction to injury. Results suggest mouse to
      be a susceptible species for turmeric induced toxicity.

PMID- 9782786
TI  - Maintenance of a Pseudomonas fluorescens plasmid in heterologous hosts: metabolic
      burden as a more reliable variable to predict plasmid instability.
AB  - The stability of a large, multiresistance plasmid, pSCL of P. fluorescens CAS102
      was studied in Pseudomonas putida and E. coli under various non-stress
      conditions. Both the strains lost the plasmid within 25 days when repeatedly
      subcultured in LB broth without any antibiotic. The transformants survived in
      sterile soil and water without any marked reduction in the viability. In sterile
      soil, P. putida lost 93% and E. coli, 98% of their plasmid containing population
      in 30 days, while in sterile water the plasmid loss was 92.5% and 97%
      respectively. The two variables, viz. the efficiency of plasmid-partitioning
      during cell division and measurement of relative specific growth rates of plasmid
      plus and plasmid-minus cells which are used to predict plasmid instability cannot
      be used to predict plasmid loss during starvation. The utility of a third
      variable, viz. the metabolic burden due to plasmid maintenance in predicting
      plasmid instability in different hosts is discussed. The rate of plasmid loss was
      found to be comparatively faster in E. coli than in P. putida. The biosynthetic
      burden due to plasmid maintenance was also more in E. coli than in P. putida when
      compared to the plasmid-plus and plasmid-minus cells of the two strains which was
      evident from the increased nutrient uptake rates (glucose, O2, and amino acid)
      and increased protein content of the plasmid-plus cells of E. coli. From the
      results, a correlation could be found between the degree of metabolic burden and
      the rate of plasmid loss. The reliability of metabolic burden, to predict plasmid
      instability versus the relative specific growth rates is discussed.

PMID- 9782787
TI  - Female gonadal sex steroids potentiate the anti-convulsant activity of phenytoin
      sodium.
AB  - Neither estrogen (E), progesterone (P), E + P nor phenytoin could protect the
      rats against maximal electroshock seizure. However phenytoin administration in
      the E, P, or E + P pre-treated animals provided significant protection in terms
      of absence of hind limb extension and a decrease in the extension/flexion ratio.
      The results suggest that there is an existing beneficial influence of the oral
      contraceptives both individually and in combination on the anti-convulsant
      activity of phenytoin, and this needs to be further probed.

PMID- 9782788
TI  - Comparative behaviour of yeast strains for ethanolic fermentation of culled apple
      juice.
AB  - The culled apple juice contained (% w/v): nitrogen, 0.036; total sugars, 11.6 and
      was of pH 3.9. Saccharomyces cerevisiae NCIM 3284, Pichia kluyeri and Candida
      krusei produced more ethanol from culled apple juice at its optimum initial pH
      4.5, whereas S. cerevisiae NCIM 3316 did so at pH 5.0. An increase in sugar
      concentration of apple juice from natural 11.6% to 20% exhibited enhanced ethanol
      production and improved fermentation efficiency of both the S. cerevisiae
      strains, whereas P. kluyveri and C. krusei produced high ethanol at 11.6% and
      16.0% sugar levels, respectively. Urea was stimulatory for ethanol production as
      well as fermentation efficiency of the yeast strains under study.

PMID- 9782789
TI  - Depression. New understanding, new drugs help to lift the weight of despair.

PMID- 9782790
TI  - Age and the next millennium.

PMID- 9782791
TI  - Dubious distinction set to end in Illinois.

PMID- 9782792
TI  - Medicare fraud: it's time to take on a new role.

PMID- 9782793
TI  - Advance planning for end-of life care.

PMID- 9782794
TI  - Curbing drug-seeking behavior.

PMID- 9782795
TI  - Dementia in the primary care setting.
AB  - The first step in assessing behavioral problems in a patient with dementia is to
      understand why these behaviors occur and what might be causing them. In some
      instances, new or longstanding problem behaviors may be related to changes
      occurring within the brain, but in other cases may be related to a physical
      problem. The second step is to determine if there is a pattern to the patient's
      behavior. Ask the caregiver to keep a behavioral log for 1 week. Analyze the log
      for any clues and triggers that may direct you toward making environmental
      changes. Once you have the behavioral log, the third step is to try and determine
      specific patterns, environmental factors or triggering events contributing to the
      behavior. In general, there are three main causes of behavioral problems:
      environment, tasks and communication. Communication between the caregiver and the
      patient affected by dementia is one of the most important and most difficult
      aspects of care. A caregiver support group may be beneficial, as well as a
      consultation with a social worker. Pharmacologic therapy should only be initiated
      if the behavioral strategies are clearly not effective after a reasonable period
      of time, the behavior has been objectively and systematically documented, or the
      patient is a clear risk to himself or others.

PMID- 9782796
TI  - Rheumatoid arthritis. Early intervention can change outcomes.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease with a predilection for
      synovial tissues, although it can affect other organs. Although the precise
      etiology is uncertain, viruses, genetics, immune dysfunction and physical trauma
      have all been implicated as causes for RA. The most basic definition, therefore,
      is that RA is inflammatory. The RA patient may have difficulty closing a fist or
      may have a week grip. The late stages of RA are easy to identify by X-ray, but to
      really perform a service for a patient, you must be able to identify its early
      stages. To do this, you must be able to examine joints. If a patient does not
      have a history of liver disease or heavy alcohol intake, methotrexate is the
      first treatment choice except in the very mildest of cases, when you can use
      NSAIDs. Steroids are sometimes an essential treatment, but use them with great
      caution and pay attention to the minimum effective dose.

PMID- 9782798
TI  - Recipe for success. Medical nutrition therapy in diabetes care.

PMID- 9782797
TI  - Colon cancer. Prevention and detection strategies.
AB  - The majority of colon cancers are adenocarcinomas originating from colonic
      epithelial tissue. Most colon tumors originate in the left side of the colon.
      Right colon tumors grow into the bowel lumen. The cause of colon cancer is not
      known, but risk factors have been identified. The three most prevalent are age,
      diet and genetics. Consumption of large amounts of fat and animal products
      increases the risk for colon cancer. Diets high in fiber and low in fat may
      protect against colon cancer due to the mucosa's more brief exposure to potential
      carcinogens. To reduce colon cancer risk in your patients, provide dietary
      counseling to promote a diet high in fiber and vitamins A, C and E. The diet
      should be low in fat, alcohol and preserved food items. Screening can reduce
      mortality rates by promoting diagnosis of cancer at an earlier, more treatable
      stage, since mortality rates increase with disease stage. Begin colon cancer
      screening of all patients at age 40 with annual digital rectal exam (DRE). At age
      50, order annual DRE and occult blood testing.

PMID- 9782799
TI  - Prostate cancer. Examining the risks and benefits of screening.

PMID- 9782801
TI  - Menopause: a new era.

PMID- 9782800
TI  - Managing and treating. AIDS-related diarrhea.
AB  - Diarrhea is a significant problem for most people with AIDS. Its causes are
      multifactorial, ranging from infectious organisms to malignancies and functional
      problems. A thorough evaluation will usually determine the etiology and guide
      treatment. With HAART, dramatic improvements in immune status have caused a
      decline in opportunistic infections, including those that cause diarrhea. It is a
      sign of hope for all patients with HIV.

PMID- 9782802
TI  - Sleep disorders. All night long.

PMID- 9782803
TI  - Advance directives. Whose death is it, anyway?

PMID- 9782804
TI  - Growth at life's end: a conversation with Ira Byock, MD. Interview by Stephen
      Cornell.

PMID- 9782805
TI  - What to do about 'nothing'.

PMID- 9782806
TI  - Arthritis Self-Efficacy Scales measure self-efficacy.

PMID- 9782807
TI  - Effect of satisfaction with one's abilities on positive and negative affect among
      individuals with recently diagnosed rheumatoid arthritis.
AB  - OBJECTIVE: The purpose of this study was to examine the effect that self
      evaluation processes have on psychologic well-being among individuals with
      rheumatoid arthritis (RA). METHODS: The study used a longitudinal research design
      with 4 data collection points. Participants were 227 adults with recently
      diagnosed RA. Data were collected via mailed questionnaire and telephone
      interview. Two dimensions of psychologic well-being were assessed--positive
      affect and negative affect. RESULTS: We found that, among participants who viewed
      the abilities being evaluated as very important, greater satisfaction at time 1
      was associated with less negative affect at time 2 and time 4. Satisfaction was
      not associated with positive affect at any of the time points, however.
      CONCLUSION: Study findings indicate that dissatisfaction with illness-related
      abilities can exacerbate psychologic distress. The findings also highlight the
      need for research examining the role that positive affect plays in adaptation to
      RA.

PMID- 9782808
TI  - Disease and family contributors to adaptation in juvenile rheumatoid arthritis
      and juvenile diabetes.
AB  - OBJECTIVE: Research in the areas of pediatric rheumatology and pediatric chronic
      illness has emphasized comprehensive models of adaptation involving risk and
      resistance factors. This study examined adaptation, within this framework, among
      a large sample of children with chronic illness and children without chronic
      illness. METHODS: A comprehensive battery of adaptation measures was administered
      to a sample of 107 children with juvenile rheumatoid arthritis, 114 children with
      insulin-dependent diabetes mellitus, and 88 healthy controls. RESULTS: Medical
      diagnosis was associated with mothers' depression and a composite measure of
      parental (mother and father) distress and passive coping. Children's emotional
      and behavioral functioning was not related to medical diagnosis, but mothers'
      depression and parental distress were associated with child behavior problems.
      CONCLUSION: Because parental distress was associated with child functioning,
      interventions to ameliorate parental distress may have beneficial effects on the
      children's behavior and on parents' reactions to their children.

PMID- 9782809
TI  - Arthritis health service utilization among the elderly: the role of urban-rural
      residence and other utilization factors.
AB  - OBJECTIVE: To compare the impact of urban-rural residence and other factors on
      the utilization of any type of arthritis-related physician care and on
      rheumatologist utilization. METHODS: A population-based random sample of adults
      65 years of age or older with self-reported arthritis from 10 urban and 12 rural
      Iowa counties were surveyed by telephone interview. We estimated the arthritis
      prevalence and health service utilization in this sample and evaluated the
      effects of predisposing, enabling, and need factors on utilization and
      satisfaction. Health care utilization was defined as ever having visited specific
      types of providers for arthritis-related care. RESULTS: A total of 488
      individuals participated: 227 from urban counties and 261 rural respondents.
      Urban respondents more commonly reported having received a diagnosis of
      osteoarthritis from their physicians but were less likely to report rheumatoid
      arthritis. A greater proportion of urban versus rural respondents had utilized
      any physician for arthritis care (50.7% versus 41.0%, P = 0.032) and had more
      often seen an orthopedist (18.1% versus 9.6%, P = 0.006) or general internist
      (18.5% versus 8.8%, P = 0.002). A diagnosis of rheumatoid arthritis, younger age,
      living with another person, higher income, and further distance from an arthritis
      provider were significantly associated with prior rheumatologist utilization. The
      strongest adjusted predictor of any physician visit for arthritis care was
      whether older adults drove themselves to their provider. For rheumatologist
      utilization, a diagnosis of rheumatoid arthritis and age were independently
      associated. CONCLUSIONS: The most striking finding was the consistent association
      of need factors (such as the desire for medical advice), joint swelling, and the
      presence of a diagnosis of rheumatoid arthritis with physician utilization. We
      identified significant urban-rural variations in factors both enabling and
      predisposing to arthritis care, although urban-rural status did not appear to
      independently influence arthritis physician utilization. In a rural state with a
      relatively small number of rheumatologists, deleterious enabling factors such as
      greater distance from the doctor and lack of supplemental insurance did not
      provide significant obstacles to either rheumatologist or generalist utilization.

PMID- 9782810
TI  - Interdisciplinary treatment for fibromyalgia syndrome: clinical and statistical
      significance.
AB  - OBJECTIVES: The primary purposes of the study were to: evaluate the treatment
      efficacy of an outpatient, interdisciplinary treatment program for fibromyalgia
      syndrome (FMS); examine whether treatment gains would be sustained for 6 months
      following the treatment; assess whether improvements were clinically significant;
      and delineate the factors associated with clinically significant improvement in
      pain severity. METHODS: Sixty-seven FMS patients completed a 4-week outpatient
      program consisting of medical, physical, psychologic, and occupational therapies.
      Six-month followup data were available for 66% of treated patients. RESULTS:
      Comparisons between pretreatment and posttreatment measures revealed significant
      improvements in pain severity, life interference, sense of control, affective
      distress, depression, perceived physical impairment, fatigue, and anxiety;
      however, there was no improvement in interpersonal relationships or general
      activities. Clinically significant improvement in pain severity, using the
      Reliable Change Index, was obtained by 42% of the sample and was predicted by the
      pretreatment levels of depression, activity, perceived disability, solicitous
      responses of significant others, and idiopathic onset. Pretreatment level of pain
      severity was not a significant predictor of the degree of pain improvement.
      Comparisons among pretreatment, posttreatment, and 6-month followup data revealed
      that the patients maintained treatment gains in pain, life interference, sense of
      control, affective distress, and depression. However, the quadratic polynomial
      analysis revealed that relapse occurred in the subjective rating of fatigue.
      CONCLUSIONS: The results suggest that, overall, an outpatient interdisciplinary
      treatment program was effective in reducing many FMS symptoms. Treatment gains
      tended to be maintained for at least 6 months. However, there were large
      individual differences in response to treatment. These results suggest that
      identification of subgroups of FMS patients and their specific clinical
      characteristics may be useful for maximizing treatment efficacy.

PMID- 9782811
TI  - Biofeedback/relaxation training and exercise interventions for fibromyalgia: a
      prospective trial.
AB  - OBJECTIVE: To compare the effectiveness of biofeedback/relaxation, exercise, and
      a combined program for the treatment of fibromyalgia. METHODS: Subjects (n = 119)
      were randomly assigned to one of 4 groups: 1) biofeedback/relaxation training, 2)
      exercise training, 3) a combination treatment, or 4) an educational/attention
      control program. RESULTS: All 3 treatment groups produced improvements in self
      efficacy for function relative to the control condition. In addition, all
      treatment groups were significantly different from the control group on tender
      point index scores, reflecting a modest deterioration by the attention control
      group rather than improvements by the treatment groups. The exercise and
      combination groups also resulted in modest improvements on a physical activity
      measure. The combination group best maintained benefits across the 2-year period.
      CONCLUSION: This study demonstrates that these 3 treatment interventions result
      in improved self-efficacy for physical function which was best maintained by the
      combination group.

PMID- 9782812
TI  - Protocol for verifying expertise in locating fibromyalgia tender points.
AB  - OBJECTIVE: To develop a protocol for determining when an individual is adequately
      trained to locate the tender points relative to fibromyalgia in an exam. METHODS:
      The error distance for each tender point was established by polling individuals
      with experience in conducting tender point exams. Bayesian statistical methods
      were employed to form a protocol for determining an individual's proficiency in
      locating the tender points. A predictive distribution was utilized to find the
      probability of remaining trained at locating tender points. Also, the probability
      of classifying at least 11 tender points as tender (mild) under different
      "locating" criteria and different number of points that are truly tender was
      computed. RESULTS: Critical values indicating the number of tender points needed
      in the qualification process for various standards of reliability--80%, 85%, and
      90%--are presented. To be certified after 3 subjects have been examined in the
      80%, 85%, and 90% criteria, one has to correctly identify 48, 50, and 52,
      respectively, out of the 54 possible tender points. CONCLUSION: We believe that
      at least 3 subjects should be examined before certification is granted using any
      of the 3 criteria--80%, 85%, and 90%. In our example, when using the 85%
      criterion, the qualification process required 7 subjects to certify an
      individual.

PMID- 9782813
TI  - A comparison of the Futuro wrist orthosis with a synthetic ThermoLyn orthosis:
      utility and clinical effectiveness.
AB  - OBJECTIVE: To compare the short-term utility and clinical effectiveness of the
      commercial-made Futuro wrist orthosis with a newly developed, custom-made
      ThermoLyn wrist orthosis. METHODS: Using a randomized cross-over trial, 10
      patients with rheumatoid arthritis used each of the two orthoses for two weeks.
      Outcome measures were patients' judgments with respect to different statements
      about utility and clinical assessments including pain and swelling of the wrist
      and finger joints, range of motion of the wrist, and grip strength. At the end of
      the study the patients were asked which of the two orthoses they preferred and
      why. RESULTS: Patients tended to favor the Futuro wrist orthosis with respect to
      pain relief and to handling the orthosis. The visual analog scale score of the
      appearance of the ThermoLyn wrist orthosis was a little higher than that of the
      Futuro wrist orthosis, but the difference was not statistically significant.
      Clinical parameters such as pain in the wrist, swelling of the wrist and finger
      joints, and movements of the wrist showed that the Futuro orthosis tended to be
      more effective than the ThermoLyn orthosis. None of the differences reached
      statistical significance. At the end of the study, 5 patients preferred the
      Futuro and 5 patients the ThermoLyn wrist orthosis. Arguments in favor of the
      ThermoLyn orthosis were better hygiene, stability, and no need to remove the
      orthosis during dirty and wet conditions. Arguments in favor of the Futuro
      orthosis were greater suppleness and freedom of movement. CONCLUSIONS: The ready
      made fabric Futuro wrist orthosis appears to be as good as the more expensive
      individually made synthetic ThermoLyn wrist orthosis with respect to short-term
      utility and clinical effectiveness. The conditions under which the orthosis will
      be worn will help to decide which orthosis is the best for the patient. In the
      event that the patient wants to use the orthosis in wet and dirty conditions, the
      ThermoLyn wrist orthosis is a good alternative to the Futuro wrist orthosis.

PMID- 9782814
TI  - It's all in an image.

PMID- 9782815
TI  - Keeping people in circulation.

PMID- 9782816
TI  - Addressing the problems of inadvertent hypothermia in surgical patients. Part 1:
      Addressing the issues.

PMID- 9782817
TI  - Sacred cows and anti-static footwear.

PMID- 9782818
TI  - Teamwork in healthcare: time for review.

PMID- 9782819
TI  - Perioperative nursing documentation in liver transplantation.

PMID- 9782820
TI  - Enhancing care using aromatherapy.

PMID- 9782821
TI  - Hello can anyone hear me?

PMID- 9782822
TI  - Exposing bad practice.

PMID- 9782823
TI  - Adrenalectomy.

PMID- 9782824
TI  - Perioperative quality assurance.

PMID- 9782825
TI  - Achieving quality.

PMID- 9782826
TI  - Reflection--a lost swab.

PMID- 9782827
TI  - Hospital acquired pressure sores as an indicator of quality: a research programme
      centred in the operating theatre.

PMID- 9782828
TI  - Addressing the problems of inadvertent hypothermia in surgical patients. Part 2:
      Self learning package.

PMID- 9782829
TI  - Can aromatherapy replace pre-medication?
AB  - An examination of the use of the therapy within the theatre environment would be
      a useful extension of the care we already give our patients. It would be
      interesting to explore the cost effectiveness of oils versus conventional
      medication, and even though there may be a negative result the desire to provide
      holistic care may overshadow the cost. If this care can be achieved through
      therapeutic touch such as massage, and enhanced by the addition of aromatic oils,
      then perhaps theatre nurses should be training to meet the needs of the patient.
      It may be appropriate therefore for studies to be undertaken into the suggested
      benefits of aromatherapy. If, as it has been implied, this therapy is beneficial
      in reducing the levels of anxiety, it would seem sensible to introduce it to
      preoperative patients who suffer varying degrees of anxiety.

PMID- 9782830
TI  - The nurse as first assistant.

PMID- 9782831
TI  - Drawing new blood into nursing.

PMID- 9782832
TI  - Who says milk and asthma don't mix?

PMID- 9782833
TI  - Caring for sexually abused clients.

PMID- 9782834
TI  - Breastfeeding and shorter hospital stays.

PMID- 9782835
TI  - Care co-ordination. An expanded role for nurses.

PMID- 9782836
TI  - Promoting a professional media image.

PMID- 9782837
TI  - The red board.

PMID- 9782839
TI  - Asthma: a personal perspective.

PMID- 9782840
TI  - What if...? Language, health care, and moral imagination.
AB  - Language is important to human life. It shapes the way we see our world, is the
      symbolic means by which we express our knowledge of the world and each other, and
      guides and justifies our actions. In addition to these roles, language conveys
      what moral ideas and values are significant to a group. These functions are
      related and not mutually exclusive.

PMID- 9782838
TI  - The view from inside. Interview by Judith Haines.

PMID- 9782841
TI  - Successful treatment for major depressive episodes.
AB  - The stigma of mental illness is powerful. Clients are afraid of being
      discriminated against if they admit they are depressed. Fifty percent of U.S.
      adults believe people with depression are simply lazy despite evidence that
      depression has biologic causes and is a treatable mental illness. In fact,
      depression is the most prevalent psychiatric disorder in the United States,
      affecting as much as 10% of the adult population. The National Institute of
      Mental Health estimates that during any 1-year period, 17.6 million U.S. adults
      suffer from a depressive illness.

PMID- 9782842
TI  - Assessing the individual with asthma.
AB  - Seven to 20 million Americans have asthma. Deaths related to asthma have
      increased 46% from 1980 to 1989. Individuals with asthma who are at risk for
      adverse outcomes are those who have low incomes and poor access to health care,
      have psychosocial problems, and do not understand or fail to follow treatment
      regimens. Additional risk factors include hospitalization within the past year, a
      previous near-fatal asthma attack, and a history of intubation for asthma.
      Assessment and appropriate treatment can prevent fatalities associated with
      asthma, especially in the home setting.

PMID- 9782843
TI  - Physical therapy in the home setting.
AB  - "Physical therapy service in the home is a changing landscape for both patients
      and providers," notes Linda H. Krulish, MHS, PT, who owns a home care contracting
      and consulting agency, Home Therapy Services, in Columbus, Ohio. Regrettably,
      physical therapy often has been defined by what it is not.

PMID- 9782844
TI  - Administering and interpreting the PPD tuberculin skin test.
AB  - Early detection and treatment are of paramount importance in our efforts to bring
      tuberculosis (TB) under control. In this context, screening high-risk populations
      for active TB and TB infection is crucial. Most individuals who become infected
      with Mycobacterium tuberculosis do not develop overt disease.

PMID- 9782845
TI  - Medication use in home care patients with COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is the fourth-leading cause of death
      in the United States. Although many other diseases have seen a gradual decline in
      their associated mortality, COPD rates have increased nearly 33% from 1979 to
      1991. The disease is defined as a slowly progressive obstruction of airflow that
      is predominantly irreversible. COPD usually begins in the fifth decade of life as
      an increased cough. Dyspnea on exertion is frequently observed in the sixth or
      seventh decade.

PMID- 9782846
TI  - When to call a physician for vein or artery problems.

PMID- 9782847
TI  - Caregiver resources. Teaching plan for COPD.

PMID- 9782848
TI  - Patient education: the key to asthma management.

PMID- 9782849
TI  - Rural research: piloting a tool to identify home care clients' risk of falling.

PMID- 9782850
TI  - The Medicare interim payment system's impact on home health services.

PMID- 9782851
TI  - National Association for Medical Equipment Services. Information systems.

PMID- 9782852
TI  - Why become accredited? Benefits and values of Joint Commission accreditation.

PMID- 9782853
TI  - Moral survival in a nontherapeutic environment.
AB  - The aim of this study was to examine the ethical decision-making process used by
      a group of psychiatric and mental health nurses in Canada. Researchers used the
      constant comparative method of grounded theory to simultaneously collect and
      analyze data. Data were collected through the use of focus groups of experienced
      psychiatric and mental health nurses. In addition to focus groups, participant
      observation and a number of formal and informal interviews were conducted. The
      contingency for the nurses in this study was the degree of support for
      professional nursing practice within the cultural context in which they worked.
      Moral survival in nontherapeutic environments was identified as the basic social
      process by which the nurses attempted to manage or ameliorate their ethical
      difficulties in their workplaces. Survival strategies included the doctor-nurse
      game, covering your backside, running interference, doctor-bashing,
      administration bashing, scapegoating, and the breakdown of teamwork. The findings
      revealed nursing strategies that were aimed at surviving in what were perceived
      as nontherapeutic environments. These strategies are morally significant because
      the dilemmas concern a moral responsibility that cannot be delegated to others.
      The moral dilemmas are whether to (a) promote one's own survival or to take care
      of patients, and (b) be held responsible for one's own actions or to place
      responsibility on others.

PMID- 9782854
TI  - Protective shield: a thematic analysis of the experience of having an adult
      sibling with insulin-dependent diabetes mellitus.
AB  - The purpose of this investigation was to describe the adult well sibling's
      experience of having grown up with a sibling who has insulin-dependent diabetes
      mellitus (IDDM). Using existential-phenomenological interview procedures, 14
      participants were asked what it was like to have a chronically ill sibling.
      Analysis of participants' experiences was done using a hermeneutical approach.
      The thematic description of the experience of having lived with a chronically ill
      sibling with IDDM was divided into two interdependent and interrelated periods,
      the past and the present. The metaphor of a protective shield woven around the
      diabetic sibling by his or her family was taken from the words of a participant,
      and is seen by participants as occurring in the past and the present. The themes
      of the past provide the background for the themes of the present. Many of the
      themes of the past are moved forward to the present, but, because of the passage
      of time, are described differently by participants. Results of this study
      reinforce the fact that the stressors of chronic illness affect all family
      members, including the well siblings. It is imperative that nurses give care to
      the family, not just the designated patient. Nurses must be prepared to provide
      counseling, education, and anticipatory guidance to adults who have a sibling
      with a chronic illness.

PMID- 9782855
TI  - Recovery from alcoholism: a spiritual journey.
AB  - The purpose of this study was to discover the internal aspects of change in
      persons who are doing well living without alcohol. The heuristic research method,
      a qualitative phenomenological design, was used to investigate the experience of
      recovery. Eight recovering alcoholics were interviewed in depth. The process of
      recovery reflected a mythological journey comprising a departure from the
      shadowland of drinking, initiation into the world of sobriety, and knowledge
      gained along the way. New adaptive strategies were acquired, including
      strengthening the will, training the mind, and exercising spiritual qualities in
      one's daily life. The profile of doing well in recovery also reflected self
      acceptance and an ongoing search for connecting with the transpersonal realm.

PMID- 9782856
TI  - Anger of African American women in the south.
AB  - In this existential-phenomenological investigation middle-class African American
      women (n = 9) in the Southern United States were interviewed about their
      experience of anger in daily life. The purpose of the study was to examine what
      African American women's anger is about, what it means, and how it is
      experienced. Transcribed interviews were analyzed using a hermeneutic process.
      The thematic structure of African American women's anger comprises three main
      elements that stand out as figural: power, control, and respect. These figural
      elements can be understood only when seen against the ground of a racist Southern
      culture that produces pervasive mistrust. These findings are of importance to
      clinicians, who cannot deliver culturally competent interventions to African
      American female clients without a clear understanding of the complexity and
      meaning of their anger experience.

PMID- 9782857
TI  - Nursing management of anxiety in HIV infection.
AB  - Anxiety is a universal problem for individuals with AIDS because the disease
      creates uncertainty and disruptions in every aspect of their lives. Nurses have a
      wide variety of holistic interventions to help persons living with AIDS (PLWAs)
      manage anxiety. Orem's self-care theory of nursing provides a framework for
      assessing, diagnosing, planning, implementing, and evaluating nursing care for an
      HIV-infected person experiencing anxiety. This article presents an overview of
      anxiety, the nature of anxiety in HIV-infected individuals, and psychological,
      pharmacological, and holistic interventions to assist the client in self-care of
      anxiety.

PMID- 9782858
TI  - The experience of fathers of adult children with schizophrenia.
AB  - The purpose of this study was to describe the lived experience of fathers of
      adult children with schizophrenia by exploring the extent to which they engaged
      in caregiving. Cross-sectional data were gathered from 12 fathers over a 2-year
      period using naturalistic inquiry. Two instruments guided in-depth explorations
      of caregiving experiences, theme extrapolation, and theme refinement. Data were
      collected during taped interviews using the constant-comparative method. Findings
      indicated that the caregiving event was prolonged. Three themes explained the
      extent to which these fathers engaged in caregiving: involvement in care,
      unresolved issues, and severity of the event. Recommendations include similar
      studies with ethnic groups and use of chronic sorrow as a framework for studies
      about parental care for adult children with severe mental illness. practice
      implications include immediate assessment of fathers, supportive listening, and
      brief therapy.

PMID- 9782859
TI  - The long journey to publication: some thoughts on the journal review process.

PMID- 9782860
TI  - Antonovsky's sense of coherence: theoretical basis of psychoeducation in
      schizophrenia.
AB  - Psychoeducational models have been found to be effective interventions for people
      with schizophrenia. However, a unifying theoretical basis for these models has
      not been articulated. This article explicates the sense of coherence theory
      developed by A. Antonovsky (1987) and demonstrates its utility as a framework for
      conceptualizing the basis for the effectiveness of psychoeducational programs.

PMID- 9782861
TI  - Environmental context of caregiving for severely mentally ill adults: an African
      American experience.
AB  - Most people with severe mental illness depend on family to provide care. Although
      an increasing amount of research has examined caregiving, there is much to be
      discovered about the caregiving experience of African American families. This
      ethnographic study reports findings from 16 African American caregivers,
      presenting a picture of how they navigate through their environment to meet the
      needs of caregiving. Formal resource selection and use, and perceived barriers to
      and facilitators of care within an urban environment, are discussed. The impact
      of the African American community's perception of mental illness on caregiving
      and involvement in policy change also is discussed.

PMID- 9782862
TI  - Empathy: a study of two types.
AB  - The time is long past for nurse researchers and educators to meet the challenge
      of scientific inquiry of those more abstract components of nursing that have been
      named the art of nursing and are now identified as dimensions of holistic
      nursing. C. Rinne (1987) stated that the art of nursing lies within the affective
      domain. Empathy is an important dimension of that domain and is focused on in the
      nursing literature. Nursing theorists prior to M. R. Alligood (1992) had not
      developed models that addressed empathy as more than a singular though
      multidimensional phenomenon. On the basis of a review of the literature in
      nursing and related disciplines, M. R. Alligood (1992) proposed two types of
      empathy: trained and basic. The purpose of this study was to examine (a) the
      differences between the two types of empathy, by evaluating scores from
      instruments that measured trained and basic empathy and (b) the endurance of
      empathy scores. Trained empathy was measured with the Layton Empathy Test, and
      basic empathy was measured with the Hogan Scale. Data were collected over time
      with 106 nursing students prior to, during, and after completion of a bachelor of
      science in nursing program at a large southeastern university. Analysis of the
      data confirmed the phenomenon of two types of empathy with differentiation in
      endurance that M. R. Alligood (1992) had proposed. The research results have
      implications for the way nursing educators prepare nurses. This study supports
      the finding that trained empathy is not sustained. The importance of measurement
      of students' baseline basic empathy is indicated. The practice of teaching
      empathy techniques is called into question, and new approaches to facilitate
      students' discovery of their basic empathy are indicated (M. R. Alligood, G. W.
      Evans, & D. L. Wilt, 1995).

PMID- 9782863
TI  - The context of sexually transmitted disease: life histories of woman abuse.
AB  - Approximately 25%-50% of women with sexually transmitted diseases (STDs),
      including AIDS, are involved in abusive relationships. Numerous characteristics
      associated with a past history of abuse are also risk factors for STD infection,
      including multiple partner relationships, substance abuse, early age at first
      coitus, and partner control of the relationship. Research has identified
      psychological effects of previous abuse, including depression, minimal control in
      relationships, and decreased self-efficacy. These effects may prevent abused
      women with STDs from making behavioral changes to prevent recurrence and
      transmission of disease. Life history methodology was used to understand the
      context of the interrelationships between STD and woman abuse in 30 Mexican
      American and African American women's lives. A focus on the context of abused
      women's partner relationships and aspects of personal control within these
      relationships may facilitate effective behavioral change, risk reduction, and
      subsequent decrease in incidence of STDs and woman abuse.

PMID- 9782864
TI  - Psychometrics for two short forms of the Center for Epidemiologic Studies
      Depression Scale.
AB  - The Center for Epidemiologic Studies-Depression Scale (CES-D; L. S. Radloff,
      1977) assesses the presence and severity of depressive symptoms occurring over
      the past week. Although it contains only 20 items, its length may preclude its
      use in a variety of clinical populations. This study evaluated psychometric
      properties of 2 shorter forms of the CES-D developed by F. J. Kohout, L. F.
      Berkman, D. A. Evans, and J. Cornoni-Huntley (1993): the Iowa form and the Boston
      form. Data were pooled from 832 women representing 6 populations. Internal
      consistency estimates, correlations with the original version of the CES-D, and
      omitted-included item correlations supported use of the Iowa form over the Boston
      form when a shortened version of the scale is desired. Regression statistics are
      provided for use in estimating scores on the original CES-D when either shortened
      form is used. Factor analytic results from two populations support a single
      factor structure for the original CES-D as well as the short forms.

PMID- 9782865
TI  - Self-care effectiveness and health outcomes in women with interstitial cystitis:
      implications for mental health clinicians.
AB  - Several researchers have discussed the need to define "outcomes" in health care
      more holistically, particularly from women's health, chronic illness, and self
      care perspectives. Interstitial cystitis (IC), a chronic illness that primarily
      affects women, is a poorly understood condition that can produce hopelessness and
      suicidal ideation. Management of IC usually requires behavioral changes in all
      life dimensions. Multidimensional health outcomes were examined in a survey of
      138 women with IC. Item-item and item-factor correlations were used to identify
      relationships between indicators of health outcomes and self-reported
      effectiveness of more than 300 self-care strategies used to manage IC. The
      effectiveness of behavioral and cognitive self-care strategies correlated
      differentially with dimensions of health. Uncertainty correlated most strongly
      with the quality of relationships with health care providers. Psychiatric nurses
      are well prepared to address the complex body-mind phenomena of IC, promoting
      effective self-care strategies while maintaining a supportive therapeutic
      relationship.

PMID- 9782866
TI  - Older? Who me? Growing old should not mean giving up.
AB  - The strangest things precipitate the most interesting discussions. It is
      interesting how frequently the word "older" appears in our language. It has been
      there all along, we have just become sensitized to its presence. The same may be
      true for you as you read the commentary on the next two pages and begin to
      reflect on the stereotypes and limitations placed on "older" people. Are they
      justified in the present day, or are they simply carryovers from the past, or is
      there some element of harsh reality to the characterizations?

PMID- 9782868
TI  - Genetic testing in Alzheimer's disease. Benefits risks and public policy.
AB  - 1. Genetic research is providing new information about the structure and function
      of genes associated with diseases such as Alzheimer's disease. 2. The ability to
      perform genetic tests to diagnose or predict disease often exists before the
      ability to prevent or treat disease. 3. Genetic tests are associated with both
      benefits and risks, which likely will apply to the Alzheimer's disease
      population. 4. Safe and effective tests, laboratories of assured quality,
      competent providers, assured privacy of genetic information, and informed
      consumers are important prerequisites to the successful integration of genetic
      tests into health care services.

PMID- 9782867
TI  - Family caregiving of hospitalized patients. Caregiver and nurse perceptions at
      admission and discharge.
AB  - To ensure patients will be discharged to stable, health-promoting home
      environments, nurses must understand family caregivers' perceptions of the
      patients' needs and problems in caring for them. At the time patients were
      admitted to and discharged from the hospital, there was little agreement between
      family caregivers and nurses about the kinds of things caregivers needed to care
      for older patients or about problems that might prevent the continuation of
      caregiving. There was slightly more overall agreement between family care-givers
      and admission nurses than discharge nurses, despite the fact that discharge
      nurses reported spending more time with patients and being more knowledgeable
      about them. Future discharge planning models should build opportunities for
      nurses to communicate with other health care colleagues who can contribute to a
      more accurate and complete picture of patients' and family caregivers' needs and
      problems in the transition from hospital to home.

PMID- 9782869
TI  - Pain and cognitive status in the institutionalized elderly: perceptions &
      interventions.
AB  - The purposes of this study were to examine the relationship between: (1) nurses'
      ratings of pain and corresponding administration of pain medication to elderly
      long-term care residents, and (2) cognitive status of the elderly and pain
      medication orders/administration. Participants were 83 residents, 60 years of age
      and older, in two groups: cognitively impaired (n = 64), and cognitively intact
      (n = 19). For comparison purposes, 19 of the cognitively impaired subjects were
      matched on age and diagnosis to provide control for potentially painful
      conditions. A retrospective medication review of the resident's charts was
      conducted to compare medication orders and administration on analgesics that were
      scheduled and p.r.n. (given as needed). The pain ratings of 25 RNs using a visual
      analogue scale were correlated with pain medications given to the resident on the
      day of the rating. Results indicated that RNs' ratings of resident pain and the
      administration of pain medications were not significantly correlated. In
      addition, cognitively impaired residents were prescribed significantly less
      scheduled medication and received significantly less pain medication (either
      p.r.n. or scheduled) than the cognitively intact elderly. Implications for
      practice and research are discussed.

PMID- 9782871
TI  - "My career focuses on the aged." At what point do you consider yourself in this
      category?

PMID- 9782870
TI  - Wandering and technology devices. Helping caregivers ensure the safety of
      confused older adults.

PMID- 9782872
TI  - The Joint Commission's ORYX initiative: implications for perinatal nursing and
      care.
AB  - In 1986, the Joint Commission on Accreditation of Healthcare Organizations
      initiated the Agenda for Change, a new era in its accreditation process,
      announcing that it would begin to incorporate outcome or performance indicators
      into its review of hospitals. The expanded focus, to include performance
      indicators, was in direct response to the rapidly changing health care
      environment. From 1987 to 1993, the Joint Commission tested five sets of
      indicators at more than 450 volunteer hospitals. In February 1996, the Joint
      Commission announced the ORYX initiative. The article reviews the history of the
      Joint Commission's Agenda for Change and highlights the new ORYX initiative, with
      particular focus on the development of the perinatal indicators and the role of
      the perinatal nurse in meeting the ORYX requirements.

PMID- 9782873
TI  - Length of stay for uncomplicated vaginal birth: a perinatal continuous quality
      improvement project.
AB  - Health care changes continue to challenge providers to reconsider how care is
      delivered. Shorter lengths of stay for mothers and newborns in California sparked
      the creation of a continuous quality improvement (CQI) project to reengineer care
      for women undergoing an uncomplicated vaginal birth. The perinatal service at the
      tertiary center discussed in the article has a birthrate of approximately 140 per
      month, about 43% of which are uncomplicated vaginal births. As a result of the
      CQI project, the length of stay decreased from 1.8 days to 1.4 days with no
      change in patient satisfaction and quality. The article illustrates the
      interdisciplinary process of CQI in the perinatal setting.

PMID- 9782874
TI  - Clinical benchmarking: implications for perinatal nursing.
AB  - Health care is a dynamic environment where expectations of quality must be
      balanced with appropriateness of treatment and cost of care. Managers often have
      inadequate information on which to base decisions, policy, and practice. Clinical
      benchmarking is a tool and a process of continuously comparing the practices and
      performances of one's operations against those of the best in the industry or the
      focused area of service and then using that information to enhance and improve
      performance and productivity. The article discusses the advantages and
      disadvantages of benchmarking as well as the factors influencing the need for
      such tools in health care and in perinatal nursing.

PMID- 9782875
TI  - Developing a service line approach to quality improvement.
AB  - A specialty hospital in New England is undergoing a radical change in its quality
      program. It is shifting from a traditional quality assurance structure with 41
      segregated committees to an integrated model based on service lines. The goals
      for this shift were fourfold: to reduce duplication of effort, to improve the
      level of integration of quality efforts across disciplines, to design a
      comprehensive system to evaluate care, and to enhance the communication of
      quality efforts. The article describes the rationale for selecting a service line
      model for performance improvement, the process of setting this change in motion,
      and the lessons learned along the way.

PMID- 9782877
TI  - The clinical experience of continuous quality improvement in the neonatal
      intensive care unit.
AB  - Central line catheters are commonly placed in extremely low-birthweight infants
      to provide venous access for administration of hyperalimentation and medications.
      Infections is the most common complication of central line catheters in this
      patient population. With expansion of the neonatal intensive care unit at
      Allegheny General Hospital and an increase in the number of infants weighing less
      than 1000 g, there was a proportionate increase in the number of central line
      catheter days. A multidisciplinary team formed to improve central line care
      practices to reduce the rate of line infections. The continuous quality
      improvement process was used to modify central line practices, which led to a
      decrease in the rate of central line infections. For the first 8 months of 1997,
      the infection rate was below the 25th percentile according to the National
      Nosocomial infections Surveillance System data.

PMID- 9782876
TI  - Quality improvement: an overview.
AB  - Clinicians are being held accountable for the quality of the care they provide in
      an unprecedented way. Quality improvement (QI), a scientifically based method,
      can help health care managers and clinicians improve health care through the
      elimination of waste and inefficiency. QI is a comprehensive approach that is
      based on an understanding of variation and uses tools specifically designed to
      help professionals understand and improve processes. The article gives an
      overview of quality improvement as a useful method for improving the process of
      clinical practice. Improving the process of care is an important step toward
      achieving quality outcomes for all health care customers.

PMID- 9782878
TI  - Outcome measures after standardized pain management strategies in postoperative
      patients in the neonatal intensive care unit.
AB  - Written guidelines based on current research on infant pain assessment and
      management were developed by an interdisciplinary team in a neonatal intensive
      care unit of a regional medical center. Charts for infants who had undergone
      abdominal surgery were reviewed to compare patient outcomes before and after use
      of this pain management protocol. With the standardization of pain management
      strategies, the following improvements were noted: decreased length of time to
      extubation, decreased length of stay, better fluid management, and reduced side
      effects of narcotics. Additional benefits included improved pain management
      documentation, decreased cost, and decreased nursing time.

PMID- 9782879
TI  - Clinical pathways for family-oriented developmental care in the intensive care
      nursery.
AB  - The physiologic and neurodevelopmental benefits of developmentally sensitive
      nursing care for high-risk infants have been well documented. The remaining
      challenge is to find ways to introduce developmental care principles into busy
      intensive care nurseries. The article discusses the development of three clinical
      pathways designed around five areas for developmental intervention: environmental
      organization, structuring of nursing care, feeding, family involvement, and
      family education. Each pathway incorporated developmental principles appropriate
      for a different level of care; the level III pathway was designed for acutely ill
      or very premature infants, the level II pathway for infants recovering from acute
      illness or older premature infants, and the level I pathway for full-term
      infants. Introduction of the developmental care pathways had an immediate
      positive impact in the tertiary level intensive care nursery at Allegheny General
      Hospital.

PMID- 9782880
TI  - Perception of threat and subjective well-being in low-risk and high-risk pregnant
      women.
AB  - The article reports a study examining the relationship between perceived threat
      and subjective well-being (positive and negative affect) in pregnant women.
      Subjects were multiparas classified as having low-risk or high-risk pregnancies
      and receiving prenatal care from private obstetricians. High-risk women were
      using home uterine activity monitoring and receiving nursing contact by telephone
      and home visit. By means of repeated measure analysis of variance, significant
      risk group differences were found in negative affect and degree of perceived
      threat. The event of the high-risk pregnancy appeared to be stressful to the high
      risk group, with high-risk pregnant women indicating more negative emotions.
      Based on the findings of this study, interventions to assist women in managing
      stress should be focused on the second trimester. A balance between personal
      support and technologic intervention is necessary.

PMID- 9782881
TI  - Pheochromocytoma in pregnancy: considerations for the advanced practice nurse.
AB  - Pheochromocytoma, a rare finding in pregnancy, is associated with significant
      risks for maternal fetal morbidity and mortality when undetected antenatally. The
      disease is commonly mistaken for hypertensive conditions of pregnancy. The
      advanced practice nurse may play a crucial role in early diagnosis based on a
      careful history and physical examination, clinical suspicion, diagnostic testing,
      and patient education. The management of a pregnant woman with pheochromocytoma
      is individualized for the woman, depending on gestational age, tumor location,
      and stabilization of the disease. A collaborative medical, surgical, and nursing
      team approach is needed. Pharmacologic intervention and surgical resection of the
      tumor(s) are the treatments of choice. Long-term followup is essential to detect
      malignancy and recurrence.

PMID- 9782882
TI  - Metabolic crisis: hyperemesis gravidarum.
AB  - Nausea and vomiting during pregnancy affect approximately 50% to 70% of all
      pregnant women. Although most cases of nausea and vomiting in pregnancy resolve
      spontaneously and are not associated with compromised nutritional status, a small
      percentage of cases progress to hyperemesis gravidarum (severe nausea and
      vomiting during pregnancy). Hyperemesis gravidarum is a serious disorder that can
      lead to weight loss, dehydration, electrolyte disturbances, and occasionally
      death if improperly treated or left untreated. The article summarizes recent
      research on hyperemesis gravidarum, focusing on the definition, etiology,
      epidemiology, and current treatment of symptoms.

PMID- 9782883
TI  - Clinical pathway for enhanced parent and preterm infant interaction through
      parent education.
AB  - The article discusses the importance of implementing a clinical pathway in the
      neonatal intensive care unit that emphasizes parent education. Through an
      extensive literature review, a clinical path was developed that incorporates
      parent education through an individualized, developmentally supportive model of
      interaction. The clinical path is designed to be utilized as a teaching tool from
      birth to discharge from the hospital. The path can serve as a guide for teaching
      and identifying learning objectives a long a time line as well as for providing
      consistent documentation.

PMID- 9782884
TI  - Prolonged exposure to a visual pattern may promote behavioral organization in
      preterm infants.
AB  - The article reports a study documenting preterm infants' responses to visual
      patterns placed in their incubators in the neonatal intensive care unit (NICU)
      and the effects of long-term exposure to the patterns. In the first experiment,
      20 preterm infants were exposed to a visual pattern in two conditions, stationary
      and rotating, during two successive exposure periods. Regardless of condition,
      the majority of infants looked longer at the visual display during the second
      exposure period and experienced decreased heart rates and quiet, alert states. In
      a second experiment, visual patterns placed in 9 preterm infants' incubators on
      transfer to the intermediate side of the NICU remained in the incubator until
      discharge. An additional 9 infants served as controls. Infants exposed to the
      visual patterns experienced fewer state changes and stronger visual skills than
      infants in incubators without visual displays. These findings, although tentative
      because of the relatively small sample sizes, suggest that visual patterns may
      promote behavioral organization and visual skills in preterm infants.

PMID- 9782886
TI  - Medical-surgical nursing: keystone of caring.

PMID- 9782885
TI  - Supporting parents during and after a pregnancy subsequent to a perinatal loss.
AB  - The experience of perinatal loss can be devastating for couples who want
      children. The decision and desire to attempt another pregnancy may be too much
      for parents to bear, yet the majority of women who experience perinatal loss do
      become pregnant again soon after the loss. A pregnancy after a perinatal loss can
      be mentally, emotionally, and physically taxing. The anxiety experienced by
      mothers during a subsequent pregnancy has been documented consistently by
      investigators, but less is known about the effects of perinatal loss on parenting
      subsequent children. Perinatal and neonatal nurses play a critical role in
      supporting parents during and after a subsequent pregnancy and need an
      understanding of the research to direct their practice.

PMID- 9782887
TI  - The next front.

PMID- 9782888
TI  - An analysis of nursing documentation as a reflection of actual nurse work.
AB  - Nursing documentation is a fundamental nursing responsibility, yet it does not
      reflect the holistic nature of nurses' practice and work. This pilot study
      investigated nurses' perceptions of the function and value of documentation and
      barriers to the documentation process.

PMID- 9782889
TI  - Acute confusion among hospitalized elders in a rural hospital.
AB  - The NEECHAM Confusion Scale was used to study the incidence and severity of acute
      confusion among elders in a rural community hospital. Thirty-eight patients over
      the age of 64 were assessed for confusion within 48 hours of admission. The
      NEECHAM Confusion Scale was readministered to a sub-sample of 17 elders within 24
      hours of pending discharge. The incidence of acute confusion was 81.5% at
      admission with a prevalence of 52.9% at discharge. Staff identified signs of
      acute confusion in 34.2% of the elders confused upon admission as indicated by
      the NEECHAM Confusion Scale. These findings have major implications for adult
      health nursing practice.

PMID- 9782890
TI  - Fibromyalgia and its primary care implications.
AB  - Fibromyalgia is a complex condition affecting up to six million patients. In this
      literature review, the prevalence, proposed etiology, differential diagnosis, and
      signs and symptoms of the disorder are presented. Diagnostic criteria, treatment
      options, and the importance of patient education are explored.

PMID- 9782891
TI  - Stroke following vertebral artery dissection: a case study.
AB  - Vertebral artery dissection is an extremely rare but serious precursor to stroke.
      A case study illustrates how accurate early assessment and diagnosis can permit
      prompt intervention. Favorable treatment outcomes can occur when such astute
      management takes place.

PMID- 9782893
TI  - AIDS: a picture of reality.

PMID- 9782892
TI  - Body temperature alterations in hospitalized HIV/AIDS patients.
AB  - Because of the questions raised by the staff nurses regarding their observations
      of fever and alterations in body temperature in AIDS patients, a nursing research
      study was conducted to examine the incidence and degree of temperature elevation
      in hospitalized AIDS patients. Study findings suggest that temperature elevation
      and fever are common occurrences in hospitalized HIV/AIDS patients, although the
      fever may be self-limiting. An elevation in the white blood cell count was not
      seen, making fever in HIV/AIDS patients different than other medical/surgical
      patients. Phenomena noted by staff nurses in the clinical setting should be
      verified by nursing research because the data derived from nursing observation
      can be used in designing nursing interventions.

PMID- 9782894
TI  - Chronic disease management offers new career opportunities.

PMID- 9782895
TI  - Quality in natural/alternative/complementary health care practice.

PMID- 9782896
TI  - Overview of cancer and genetics: implications for nurse practitioners.
AB  - The understanding of cancer at a molecular level and of the contribution of
      certain genetic mutations to the development of cancer is progressing at an
      unparalleled rate. Advances in technology and discoveries stemming from the Human
      Genome Project now provide the means to test individuals for the presence of
      mutations associated with some known hereditary cancer syndromes. Although many
      ethical, legal, and psychosocial issues associated with testing remain
      unresolved, predisposition genetic testing is having and will continue to have a
      significant impact on health care. Nurse practitioners will play a vital role in
      assessing clients for increased risk of developing cancer, educating clients
      about the availability of testing, making referrals for cancer genetic counseling
      and risk assessment, and providing follow-up care in the community for patients
      found to be at increased risk.

PMID- 9782897
TI  - Overview of cancer prevention, screening, and detection.
AB  - Greater than one in three Americans will be diagnosed with cancer during their
      lifetime. Nurse practitioners are in an ideal position to significantly impact
      the health and well-being of their clients by implementing cancer prevention and
      screening strategies. This article reviews current recommendations from major
      authorities and outlines cancer prevention and screening strategies to be
      incorporated into primary care practice.

PMID- 9782898
TI  - Hormone replacement therapy.
AB  - For the large number of women who become menopausal each year, the decision of
      whether to use hormone replacement therapy is central. The author outlines
      treatment options, risks, and benefits of hormone therapy and examines
      likelihoods of outcomes. Based on the latest research, types of hormones
      available, prescription regimens, side effects, and alternatives to hormone
      therapy are discussed.

PMID- 9782899
TI  - Cancer-related neuropathic pain.
AB  - Neuropathic pain refers to syndromes that may be related to peripheral or central
      neural structure compression, infiltration, or damage. Cancer-related neuropathic
      pain results from compression or infiltration of nerves by the tumor, nerve
      trauma from operative procedures, or neuropathic pain related to cancer
      treatment. Management of neuropathic pain includes the use of opioids,
      antidepressants, anticonvulsants, local anesthetics, and other adjuvant
      medications. Intractable neuropathic pain may require the use of intraspinal
      delivery or anesthetic and neurosurgical procedures. The nurse practitioner plays
      an important role in the assessment and "trial and error" management of cancer
      related neuropathic pain.

PMID- 9782900
TI  - Deep venous thrombosis.
AB  - Deep venous thrombosis (DVT) is an important clinical condition accounting for
      600,000 hospitalized patients in North America per year. Signs and symptoms of
      DVT are nebulous and often absent. Pulmonary embolus is often a coexisting
      condition and is most often caused by DVT. Both require anticoagulation and
      possibly thrombolytic therapy. There is a long list of risk factors that
      predispose a patient to DVT including cancer, cardiac disease, and hereditary
      conditions. This article examines predisposing factors, diagnostic tools,
      treatment, and sequela of DVT.

PMID- 9782901
TI  - Fever of unknown origin.
AB  - Despite substantial advances in antimicrobial therapy, infection remains a major
      cause of morbidity and mortality in immunocompromised cancer patients. As more
      intensive, curative antineoplastic treatment regimens are established, the risk
      for fatal infectious complications will continue to rise. Signs and symptoms of
      infection in this compromised population may be subtle; yet, an undetected and
      untreated infection can quickly evolve into septic shock and death. Typically,
      fever is considered to be a clinical hallmark of infection. Yet, most patients
      initially present to the clinical setting with a fever of unknown origin. Given
      the lethal nature of infections in immunocompromised patients, one must assume
      that the febrile patient is infected until proven otherwise.

PMID- 9782903
TI  - Hypothyroidism in cancer patients.
AB  - Hypothyroidism as a manifestation of malignancy, as a comorbid disorder in cancer
      patients, and its treatment are of significant importance to the advanced
      practice nurse. Considering that the incidence of hypothyroidism reaches 50% to
      80% in some cancer patient populations, it is of concern that this problem is
      rarely addressed in standard oncology texts and journals. This article addresses
      the unique relationship of hypothyroidism to cancer patients and the important
      role of the advanced practice nurse in assessing and managing this complex
      disorder.

PMID- 9782902
TI  - Long-term cardiac and pulmonary complications in cancer care.
AB  - Advances in cancer treatment are responsible for longer overall survival in
      patients with cancer. As a result of high-dose intensity and multimodal treatment
      regimens, these individuals are at risk for long-term complications. The heart
      and lungs are common sites of cancer recurrence as well as targets of damage from
      radiation and chemotherapy. Primary care nurse practitioners need to be aware of
      these late complications and consider these in a differential diagnosis when a
      patient presents with cardiac and pulmonary problems and has a history of cancer.

PMID- 9782904
TI  - The long-term cancer survivor: a challenge for nurse practitioners.
AB  - For approximately 8 million Americans alive today, the words "cancer" and
      "survival" are no longer mutually exclusive. As advances are made in the early
      detection and treatment of cancer, the numbers of survivors who are recovering
      from their illnesses or living longer with cancer as a chronic disease are
      increasing. With this extended survival comes a new set of responsibilities and
      standards for follow-up care that include the following: (1) the recognition of
      chronic or potential problems, (2) the need for life-long surveillance, and (3)
      continued access to quality health care. Long-term follow-up care for cancer
      survivors can be a specialty unto itself. The development of clinics or programs
      that specialize in caring for this expanding population have a history within
      pediatric oncology. The challenge in the current health care market is to
      dedicate energy and resources to do the same within the adult oncology community.
      Nurse practitioners are ideal candidates to create holistic programs that focus
      on the special needs, both biomedical and psychosocial, of long-term cancer
      survivors.

PMID- 9782905
TI  - Nursing diagnoses and outcomes.

PMID- 9782906
TI  - Cognitive development among nurses.

PMID- 9782907
TI  - Nursing diagnoses in patients with leukemia.
AB  - PURPOSE: To identify and describe nursing diagnoses, their related factors, and
      defining characteristics, in hospitalized leukemia patients and to categorize
      these nursing diagnoses within Functional Health Patterns. METHODS: Content
      analysis of 15 nursing records and interviews with 7 oncology nurses working on a
      hematology/oncology ward in a University hospital in Maastricht, the Netherlands.
      FINDINGS: In the leukemia population, 47 nursing diagnoses with their associated
      characteristics were identified and classified within 10 Functional Health
      Patterns. Most of the nursing diagnoses were related to the Nutritional
      Metabolic, the Cognitive-Perceptual, Activity-Exercise, the Role-Relationship,
      and the Coping-Stress-Tolerance patterns. CONCLUSIONS: Results describe the
      nursing care needs of patients with leukemia. Since the study used a small
      sample, results should be interpreted with caution. Further research is
      recommended.

PMID- 9782908
TI  - Teaching baccalaureate nursing students to project outcomes to nursing
      interventions.
AB  - PURPOSE: To develop an innovative method of teaching baccalaureate nursing
      students to plan for and recognize outcomes to specific nursing interventions.
      METHODS: A case study design that measured the effectiveness of a teaching
      innovation. Tools for students (N = 8) to use during clinical practice included
      an Intervention-Outcome Analysis Tool and a Nursing Clinical Outcomes Tool.
      FINDINGS: Quantitative and qualitative evaluation data were presented that showed
      growth in the ability to set and meet patient outcomes during the semester.
      CONCLUSIONS: Thinking in terms of outcomes moved student beyond problem solving
      in their clinical thinking and assisted them to learn to develop individualized
      outcome statements for their patients.

PMID- 9782909
TI  - Predictive power of clinical indicators for self-care deficit.
AB  - PURPOSE: To describe the predictive power of a set of the best clinical
      indicators for the nursing diagnostic labels self-care deficit (SCD) and impaired
      physical mobility. METHODS: Patient assessment data (physical examination and
      interview) were obtained from 414 hospitalized patients. FINDINGS: Patients with
      the diagnostic label of self-care deficit were significantly older in age, had a
      greater number of nursing diagnoses, required greater assistance in activities of
      daily living, and were less mobile than those without the diagnostic label. While
      18 of 32 clinical indicators were positively related to self-care deficit, five
      clinical indicators were sufficient to diagnose SCD. CONCLUSIONS: Further
      development of the method may be useful in improving diagnostic accuracy and
      efficiency of nursing diagnoses.

PMID- 9782910
TI  - Accuracy of nurses' diagnoses: foundation of NANDA, NIC, and NOC.

PMID- 9782911
TI  - You make the diagnosis. Case study: clinical opportunities and challenges related
      to diagnosis of and interventions for loss of control.

PMID- 9782912
TI  - The influence of nursing diagnosis on information processing by undergraduate
      students.
AB  - PURPOSE: To examine the influence of a nursing diagnosis course on the
      information processing by undergraduate students. METHODS: A quasi-experimental
      study conducted with two groups (experimental, n = 15; control, n = 22) of
      undergraduate nursing students, subjecting only one to a nursing diagnosis
      course. The students' ability to identify, cluster, and name clusters of relevant
      data were compared between and within groups. FINDINGS: After the course, the
      experimental group performed better than the control group in the three
      activities studied. CONCLUSIONS: The results of this study suggest that the
      nursing diagnosis content in teaching favors clinical reasoning to determine the
      patient's nursing care.

PMID- 9782913
TI  - Nursing diagnoses and interventions for post-acute-phase battered women.
AB  - PURPOSE: To identify nursing diagnoses and interventions applicable for post
      acute-phase battered women. METHODS: Eight battered women were interviewed twice
      for 2 hours. Gordon's functional health patterns provided the framework for data
      collection. FINDINGS: Fifty-three nursing diagnoses and 52 nursing interventions
      were indicated in the data; 24 nursing diagnoses and 26 nursing interventions
      were present in all participants' data. CONCLUSIONS: With the use of
      comprehensive interventions, nurses can make a major contribution to society by
      enabling battered women to move to a more protected lifestyle.

PMID- 9782914
TI  - Nursing diagnosis in the International Classification for Nursing Practice
      (ICNP).
AB  - TOPIC: International Classification for Nursing Practice (ICNP) Classification of
      Nursing Phenomena. PURPOSE: Provide a historical review of nursing diagnosis in
      the developing ICNP. SOURCES: Literature, meeting notes, and experience.
      CONCLUSION: The development of the ICNP has benefited from contributions of many.
      Continued refinement depends on participation of nurses globally.

PMID- 9782915
TI  - Beneficent voluntary active euthanasia: a challenge to professionals caring for
      terminally ill patients.
AB  - Euthanasia has once again become headline news in the UK, with the announcement
      by Dr Michael Irwin, a former medical director of the United Nations, that he has
      helped at least 50 people to die, including two between February and July 1997.
      He has been quoted as saying that his 'conscience is clear' and that the time has
      come to confront the issue of euthanasia. For the purposes of this article, the
      term 'beneficient voluntary active euthanasia' (BVAE) will be used: beneficient
      from the prima facie principle of beneficience, to do good, and voluntary to
      indicate that this must be carried out at the request of a competent client. This
      implies adherence to another prima facie principle, that of respect for autonomy.
      Active implies that something is done or given with the intention of hastening
      death. The word euthanasia itself simply means 'good death'. This article
      examines the moral positions of two nurses and one junior doctor towards the
      subject of BVAE and an attempt is made to represent the main conflicting moral
      positions. The central arguments against BVAE and counterarguments are presented.
      The conclusion reached is that consenting adults should not be prevented from
      availing themselves of BVAE if another consenting adult (a medical doctor) is
      available and capable of carrying out their wishes. This being the case, it is
      suggested that BVAE should be available as an option in hospices and in the
      community. The aims of this article are: to generate debate among professionals;
      to present a three-way discussion that might be useful as a focus for educational
      purposes, particularly at undergraduate level; to challenge professionals to
      confront the issue of euthanasia; and to plead the case of those who request
      assistance in exercising autonomy by gaining control over their own deaths.

PMID- 9782916
TI  - Ethical dilemmas in the care of patients with incurable cancer.
AB  - This article aims to identify and describe the ethical dilemmas that are involved
      in the care of patients with incurable cancer. The data were collected in
      semistructured focused interviews with 32 patients, 13 nurses and 13 doctors from
      two central hospitals and four community health centres. The interviews were tape
      recorded and transcribed verbatim. Interpretation was based on the method of
      content analysis. Ethical dilemmas occurred at the time of diagnosis, in
      connection with telling the truth, in providing information, in the treatment of
      pain, and in decision-making situations concerning active treatment. Dilemmas of
      active treatment concerned chemotherapy, intravenous infusions, blood
      transfusions and antibiotics. There were also problems in relationships between
      nursing staff and next of kin, as well as a lack of co-operation between nurses
      and doctors.

PMID- 9782917
TI  - An ethical perspective on euthanasia and assisted suicide in The Netherlands from
      a nursing point of view.
AB  - In the Netherlands, euthanasia and assisted suicide are formally forbidden by
      criminal law, but, under certain strictly formulated conditions, physicians are
      excused for administering these to patients on the basis of necessity. These
      conditions are bound up with a long process of criteria development. Therefore,
      physicians still live in uncertainty. Future court decisions may change the
      criteria. Apart from that, physicians can always be prosecuted. The position of
      nurses, however, is perfectly clear; they are never allowed to administer
      euthanasia or assisted suicide. Nevertheless, they should be involved in the
      decision-making process because they are an important source of information and
      have consultation skills. The openness of the discussion about these issues in
      the Netherlands may prevent an escalation of medical or nursing responsibility
      and falling victim to the 'slippery slope'.

PMID- 9782919
TI  - Administrative decision making in response to sudden health care agency funding
      reductions: is there a role for ethics?
AB  - In October 1993, a survey of health care agency administrators was undertaken
      shortly after they had experienced two sudden reductions in public funding. The
      purpose of this investigation was to gain insight into the role of ethics in
      health administrator decision making. A mail questionnaire was designed for this
      purpose. Descriptive statistics and content analysis were used to summarize the
      data. Staff reductions and bed closures were the two most frequently reported
      mechanisms for addressing the funding reductions. Most administrators did not
      believe that these changes would have a negative public impact. In contrast, the
      majority indicated that future changes in reaction to additional funding
      reductions would have a negative public impact. Approximately one-third of the
      administrators reported ethics to be an element of recent administrative decision
      making, and one-half could foresee that ethics would be important in the future
      if reductions continued. These findings are discussed in relation to ethics.
      Issues for additional research are outlined.

PMID- 9782918
TI  - Physical restraint: a descriptive study in Swiss nursing homes.
AB  - This article focuses on the reasons for using physical restraints, their
      prevalence and nurses' experiences of their use. The data were collected by means
      of a questionnaire from nurses, trained nurse's aids and auxiliary staff (n =
      173) in seven Swiss nursing homes. The results showed that physical restraints
      are used in nursing units, the mean number of restrained residents in each being
      3.7 (SD 3.9). However, nursing staff did not necessarily understand and consider
      the term 'restraint' as a restrictive device in its negative sense. The most
      common reasons indicated for the use of restraint were related to the protection
      and safety of the residents themselves, the prevention of disturbance of other
      residents, and the residents' restlessness and aggressiveness. As for the reasons
      related to staffing, reference was made to understaffing, a lack of competence on
      the part of nurses, and the demands of residents, their next of kin and doctors.
      It was not common practice to inform the elderly residents that they would be
      restrained, and therefore they were not always aware of what was happening to
      them and why. Twenty-nine per cent of the respondents reported that the
      flexbility of their work was affected by the use of physical restraint.

PMID- 9782920
TI  - Information disclosure: the moral experience of nurses in China.
AB  - While the movement to ensure patient's rights to information and informed consent
      spreads throughout the world, patient rights of this kind have yet to be
      introduced in mainland China. Nonetheless, China is no different from other parts
      of the world in that nurses are expected to shoulder the responsibility of
      safeguarding patients' best interests and at the same time to uphold their right
      to information. This paper expounds on the principle of protectiveness grounded
      in traditional Chinese medical ethics concerning the practice of informed
      consent. Nurses in China have a moral obligation to treat patients with
      sincerity. This notion carries a strong sense of parental protectiveness. As far
      as information-giving is concerned, nurses in China are ambivalent about the
      notion of truthfulness. The findings of an empirical study undertaken in seven
      Chinese cities reveal that nurses in China experience similar difficulties
      related to the disclosure of information as their counterparts in other parts of
      the world. A nurse's narrative, the Chan case, is used to illustrate the typical
      difficult situation that nurses in China often encounter in looking after
      vulnerable patients who would like to learn more about their therapeutic
      regimens. The moral tension embedded in nursing practice is analysed. It is found
      that most nurses would prefer to tell the truth to patients, but their primary
      ethical justification is not that of respect for patients' autonomy or
      safeguarding patients' right to self-determination. Rather, it is basically
      beneficent in nature; that is, they base their decision to reveal the truth on
      whether or not patients will receive more relevant treatment and better nursing
      care.

PMID- 9782921
TI  - Using clients: a response to Paul Cain.

PMID- 9782922
TI  - National Council for Hospice and Specialist Palliative Care Services. Voluntary
      euthanasia: the council's view.

PMID- 9782923
TI  - Sensitive judgement: an inquiry into the foundations of nursing ethics.
AB  - This article considers the foundation of nursing as a moral practice. Its basic
      claim is that all nursing knowledge and action reside on a moral foundation. The
      clinical gaze meets vulnerability in the patient's human condition. To see a
      patient's wound is to see his or her hurt and discomfort; it is a concerned
      observation. To see the factual and pathophysiological is at the same time to see
      the ethical: the moral realities of suffering, pain and discomfort. A nurse's
      emotional sensitivities are central to understanding a patient's experiences of
      illness. Emotions reveal value and ascribe moral importance to certain
      situations; they are addressed centrally by vulnerability and the moral realities
      of illness. Hence, the essence of nursing knowledge and nursing performance
      cannot be understood merely as ontology (i.e., as being-with-the-other). Nursing
      is basically being-for-the-other; it is responsibility; it is ethics.

PMID- 9782924
TI  - The art of nursing.
AB  - This article discusses the question of whether, as is often claimed, nursing is
      properly described as an art. Following critical remarks on the claims of Carper,
      Chinn and Watson, and Johnson, the account of art provided by RG Collingwood is
      described, with particular reference to his influential distinction between art
      and craft. The question of whether nursing is best described as an art or a craft
      is then discussed. The conclusion is advanced that nursing cannot properly be
      described as an art, given acceptance of Collingwood's influential definition of
      art. Moreover, it is shown that, due to difficulties inherent in specifying the
      'ends' of nursing, nursing is only problematically described as a craft.

PMID- 9782925
TI  - The art of nursing: an aesthetics?
AB  - This article explores the question of whether or not the 'art' of nursing can
      properly be described as an 'aesthetics'. The author concludes that, although
      much nursing literature on the subject is confused and even incoherent, there is
      nevertheless some justification for seeing a connection between the art of
      nursing and aesthetics. The philosophical writings of Martha Nussbaum and Iris
      Murdoch are used to support this position.

PMID- 9782926
TI  - Informed consent in a multicultural cancer patient population: implications for
      nursing practice.
AB  - Obtaining informed consent, an ethical obligation of nurses and other health care
      providers, occurs routinely when patients make health care decisions. The values
      underlying informed consent (promotion of patients' well-being and respect for
      their self-determination) are embedded in the dominant American culture. Nurses
      who apply the USA's cultural values of informed consent when caring for patients
      who come from other cultures encounter some ethical dilemmas. This descriptive
      study, conducted with Latino, Chinese and Anglo-American cancer patients in a
      large, public, west-coast clinic, describes constraints on the informed consent
      process in a multicultural setting, including language barriers, the clinical
      environment, control in decision making, and conflicting desired health outcomes
      for health care providers and patients, and suggests some implications for
      nursing practice.

PMID- 9782927
TI  - Cultivating a moral sense of nursing through model emulation.
AB  - This paper reports part of a longitudinal research project, which sought to
      capture students' conceptualization of caring practice as they progressed to
      different levels of study in a nursing diploma programme in Hong Kong. Model
      emulation was found to be an effective means of focusing students' learning
      processes on the moral aspects of nursing practice. The theory of model emulation
      from a Chinese perspective and how it is applied to create a learning context to
      allow students to acquire a moral sense of nursing are discussed. The
      participating students are invited to be sincere enquirers in the pursuit of the
      good embedded in practice through introspective self-examination and dialogue.
      They are asked to describe and share their experience of positive and negative
      examples of nursing in written accounts. Van Kaam's phenomenological method was
      adopted to explicate the good and bad constituents of nursing from these
      examples, with the students assuming an active role in the explication process.
      The explication reveals that the students were able to articulate the good and
      bad practices in a variety of patient care situations.

PMID- 9782928
TI  - Tensions in sharing client confidences while respecting autonomy: implications
      for interprofessional practice.
AB  - This article aims to explore the ethical issues arising from the sharing of
      information in the context of interprofessional collaboration. The increased
      emphasis on interprofessional working has highlighted the need for greater
      collaboration and sharing of client information. Through the medium of a case
      study, we identify a number of tensions that arise from collaborative
      relationships, which are not conducive to supporting interprofessional working in
      an ethically sound manner. Within this article, it is argued that the way forward
      within these collaborative relationships is to set clear parameters to the
      professional-client relationship, paying full regard to the autonomy of both the
      clients and the professionals involved. We conclude that this approach to working
      will place the client at the centre of care provision and arguments used for not
      collaborating that are based on breaches of confidentiality will be negated.
      Using the approach offered, collaborative working will be not only possible but
      desirable.

PMID- 9782930
TI  - In search of the truth or Jerry Springer.

PMID- 9782929
TI  - What we owe the author: rethinking editorial peer review.
AB  - Editorial peer reviewers play an important role in shaping the direction of
      knowledge growth of their discipline. Recent concern over reports of peer review
      misconduct has led some to advocate the establishment of a code of ethics for
      peer reviewers. Such a code should include guidelines for the discipline and for
      society at large, but it should also contain guidelines for the authors whose
      manuscripts are reviewed. Peer reviewers have a special obligation to show
      beneficence and fairness or impartiality towards the authors for whom they
      review. The practical application of these two ethical concepts is discussed.

PMID- 9782931
TI  - Tenure: viable or a dinosaur?
AB  - This article discusses the history of tenure in academia as well as the current
      pros and cons of the tenure system. A review of nursing and non-nursing
      literature reveals that the most important goal confronting the nation's
      universities and colleges today is to find more creative ways to define scholarly
      work and incorporate it into promotion and tenure guidelines. The author presents
      arguments for and against tenure, reviews the impact of tenure in nursing, and
      offers recommendations and solutions to the tenure dilemma in nursing.

PMID- 9782932
TI  - Should alternative treatment be integrated into mainstream medicine?
AB  - Healthcare providers and patients are becoming increasingly aware of the options
      available with alternative medicine or unconventional therapies. This article
      analyzes alternative medicine, examines rationale for its existence, and outlines
      some concerns. The author concludes that nurses must take the lead and become
      educated about this option in healthcare treatments in order to help patients
      make informed decisions.

PMID- 9782933
TI  - Overconfidence: a concept analysis.
AB  - Overconfidence has an effect on clinical practice and patient outcomes. The
      author utilizes Walker and Avant's procedure for conceptual analysis to give a
      systematic definition to overconfidence as it relates to decision-making in
      nursing. The characteristics that demonstrate the presence of overconfidence are:
      (a) failure to consider alternative perspectives, (b) failure to distinguish
      inferences from assertions, (c) favoring positive over negative information, (d)
      unwarranted certainty in the prediction of accuracy, and (e) control. An
      increased awareness of the existence of overconfidence can increase the
      reliability of nursing judgment.

PMID- 9782935
TI  - Complementary care ... begins at home.

PMID- 9782934
TI  - One practice week at a glance. Lynda Juall Carpenito, family nurse practitioner.

PMID- 9782936
TI  - Moving toward the next millennium.

PMID- 9782937
TI  - Capital issues for ORL nurses.
AB  - As the 1997 Nurse in Washington Intern for SOHN, I was awed by the quality and
      quantity of information and experiences shared during the workshop. The three
      major concerns in healthcare policy on Capitol Hill are cost, quality, and
      access. Healthcare costs have escalated at tremendous speed, bypassing the growth
      of the Gross Domestic Product. Medicare is projected to go broke by 2007. The
      United States population is aging rapidly. The Federal Government must make
      changes to Medicare and Medicaid legislation or the U.S. Treasury may be
      consumed. As costs are cut, quality and access must be ensured. These are years
      of rapid change in healthcare. Nurses face many challenges and have many
      opportunities to participate in and influence the formation of healthcare policy.
      Nurses must be armed with information about key players, the processes, and what
      nursing can contribute to the healthcare system. We need to step up to the plate;
      we need to be part of the solution.

PMID- 9782939
TI  - The National Oral Cancer Awareness Program.
AB  - The National Oral Cancer Awareness Program (NOCAP) is a comprehensive,
      multidisciplinary program aimed at increasing public and professional awareness
      of oral cancer. The objective of NOCAP is to facilitate cooperation among the
      various healthcare disciplines involved in oral cancer detection, diagnosis,
      treatment, and patient rehabilitation, in order to reduce the incidence,
      mortality, and morbidity, of oral cancer through education-based prevention and
      early detection programs. Nurses play a definitive role in patient education and
      should therefore become a part of this cooperative effort.

PMID- 9782938
TI  - Unit-based education: meeting the needs of staff nurses in the '90s.
AB  - Staff development is an integral component of nursing and plays a vital role in
      the development and maintenance of nursing competency. Currently, nursing staff
      development departments are facing reductions in size due to financial concerns
      of the institutions. These reductions in size result in decreased educational
      support available to each staff nurse at the unit level. This article will
      discuss the history of nursing staff development, as well as an innovative way to
      meet current educational needs of staff nurses.

PMID- 9782940
TI  - Literature review on quality of life following head and neck cancer: 1996-1997.

PMID- 9782941
TI  - The renaissance begins with you ... the search is on for best practices.
AB  - A new spirit of innovation is arising in health care. Just as the historical
      renaissance opened new frontiers of European art, architecture, science, and
      literature, we have the opportunity to release a new wave of innovation that will
      revolutionize healthcare delivery. The means are near at hand. Never before has
      our knowledge been so deep, technology so powerful, or communications so fast and
      wide. Yet, like medieval scholars, isolated in our monasteries, we have so far
      had limited effect in positively changing the system. Real change begins today-
      as soon as we begin talking to one another, comparing our experiences, sharing
      our problems, devising solutions, and imagining the future together.

PMID- 9782942
TI  - [Open curriculum. Optimism, openmindedness, beginning, joy, chance, time, mood].

PMID- 9782944
TI  - [Concerning: resume of a geriatric nurse visiting a congress for the first time]

PMID- 9782943
TI  - [Let us listen to the victims ... mobbing is a phenomenon that can happen to
      anyone. Therefore let us be careful].

PMID- 9782945
TI  - [Nursing at home--learning from the professionals. A new branch of education for
      family caregivers at the health academy of the Klagenfurt nursing school].

PMID- 9782946
TI  - [International classification for nursing practice--development of a proper
      nursing language].

PMID- 9782947
TI  - [Beyond the border ... a look at the nursing situation in Europe. An-incomplete
      review which we are continuing in loose sequence] [In Process Citation]

PMID- 9782948
TI  - [Functional independence measure (FIM)].

PMID- 9782949
TI  - [Mobbing in the work place. Catchword or sad reality].

PMID- 9782950
TI  - [Mobbing in nursing].

PMID- 9782951
TI  - [Mobbing--from the viewpoint of leadership].

PMID- 9782952
TI  - [Mobbing--psychological violence in the workplace].

PMID- 9782954
TI  - [Student today--coworker tomorrow. An empirical study of the ARGE "Evaluation of
      the practical education of nursing students at the Graz General Nursing School"].

PMID- 9782953
TI  - [Nursing documentation in emergency services conforming to legislation-
      impossible?].

PMID- 9782955
TI  - Foresight.

PMID- 9782956
TI  - Maintaining confidentiality and privacy in case study presentations: implications
      for wound care education.
AB  - Wound care professionals are often called upon to prepare others to care for
      patients with chronic and other forms of skin injury. Case presentations offer a
      creative and meaningful approach in teaching assessment and treatment options.
      However, case presentations pose threats to patient confidentiality and privacy.
      Using a clinical situation, confidentiality and privacy issues that can arise
      from these case presentations are briefly described and recommendations are
      provided to enable clinicians to avoid situations that violate the patient's
      privacy.

PMID- 9782958
TI  - Bacteria for the nineties.
AB  - Staphylococcus aureus and Enterococci have gained prominence as the causes of
      wound infections during this decade. Methicillin-resistant Staphylococcus aureus
      (MRSA) became commonplace in the United States during the 1980s. In Canada,
      infections with MRSA have been increasing in frequency since 1995. MRSA develops
      resistance by producing an altered penicillin-binding protein, PBP 2a, coded for
      by the mecA gene. Vancomycin is the usual drug of choice. Recently, strains with
      intermediate resistance to vancomycin (VISA) have been isolated from patients in
      Japan and the United States. Interim guidelines for their control have been
      developed by the Centers for Disease Control. Enterococci have developed a
      resistance to a variety of antimicrobials during the past three decades,
      including beta-lactams and aminoglycosides. Recently, strains resistant to
      vancomycin (VRE) have been found in the United States and Canada. They are
      particularly difficult to treat, although some success has been achieved with
      experimental drugs. These microorganisms have the ability to escape control by
      antimicrobials almost as soon as they are developed. Thus, we must practice good
      infection control and reserve antimicrobials only for clear cases of infection if
      we are to prevent or delay the emergence of resistance.

PMID- 9782957
TI  - The basic principles of wound care.
AB  - A chronic wound should prompt a search for the underlying causes. Knowledge of
      the physiology of the normal wound healing trajectory through the stages of
      hemostasis, inflammation, granulation, and maturation provides a framework for
      understanding the advantages of moist interactive wound healing. Good chronic
      wound care is patient-centered, holistic, interdisciplinary, and evidence-based.

PMID- 9782960
TI  - Wound infection: a physician's perspective.
AB  - Infection in a wound represents a colony count of 10(5) or greater. Contamination
      is the presence of many surface organisms. Moist wound healing, not dehydration,
      protects and prepares the wound for coverage and closure. Relief of pain is a
      critical factor in achieving healing: a biological or pharmaceutical device can
      achieve protection and facilitate healing.

PMID- 9782959
TI  - Wound infection: a nurse's perspective.
AB  - There is clinical uncertainty about the involvement of bacteria in open wounds.
      Frequently asked questions are: Is this wound infected? Should I culture the
      wound? How should I clean the wound? Do I need to use sterile technique when I
      perform local wound care? Using available science and common sense, a practical
      approach is proposed to answer these questions.

PMID- 9782962
TI  - Latex allergy: a problem for both healthcare professionals and patients.
AB  - Immediate hypersensitivity responses to natural rubber latex (NRL) products have
      been recognized with increasing frequency in North America since 1989. The
      allergic response occurs to one or more NRL proteins, resulting in contact
      urticaria, angioedema, allergic rhinitis, asthma, or anaphylaxis. Early
      recognition of sensitization to NRL is crucial to prevent the occurrence of life
      threatening reactions in sensitized healthcare providers and their patients.

PMID- 9782963
TI  - 'Nobody asks me what I want!'.

PMID- 9782961
TI  - Hand eczema.
AB  - Hand eczema is a common disorder of healthcare providers. The pattern of eczema
      can help to distinguish endogenous (dyshidrosis, atopy) causes from exogenous
      (contact irritant and allergic dermatitis) and the common differential diagnoses
      (psoriasis, fungus infections). Appropriate strength topical steroids,
      moisturizers, antibacterials, and systemic agents are all used to treat hand
      eczema depending on the type of eczema and its severity. Patients with contact
      allergic eczema should be assessed for possible latex allergy.

PMID- 9782964
TI  - Imposing western aid: success or failure?

PMID- 9782965
TI  - The importance of sleep following ENT surgery.
AB  - This study reviewed a group of 48 children following ENT surgery and considered
      the implications of too little sleep after their operation. All the children had
      either an adenoidectomy, a tonsillectomy, or an adenotonsillectomy. Their post
      operative sleep was timed and their state of nausea was recorded when they awoke.
      There appeared to be a correlation between the length of undisturbed sleep and
      the incidence of nausea or vomiting. It is suggested that this result should
      influence the advice given to parents of the benefits about sleep for their child
      in the post-operative period.

PMID- 9782966
TI  - Auditing paediatric pain management.

PMID- 9782967
TI  - Peplau's model in mental health nursing.

PMID- 9782968
TI  - Phantom limb pain following amputation.

PMID- 9782969
TI  - Numeracy skills.

PMID- 9782970
TI  - The science of nursing.

PMID- 9782971
TI  - Communication and quality care.

PMID- 9782972
TI  - Interferon therapy for MS.

PMID- 9782973
TI  - Nurses' perceptions of good nursing care.
AB  - Nursing has been described as 'caring for patients'. By telling stories about
      their experiences nurses may define what they understand to be good nursing care.
      Nurses' narratives emphasised the importance of building up a rapport with a
      patient to overcome fears, provide assistance and diffuse difficult situations.

PMID- 9782974
TI  - A non-pharmacological approach to angina.
AB  - Chronic angina is a debilitating condition that can severely limit physical
      activity and lead to depression. Patients whose angina is not susceptible to
      acute surgical or pharmacological interventions may be offered no further
      palliative solutions. Non-pharmacological interventions such as TENS, spinal cord
      stimulation, music therapy, relaxation and humour warrant further research and
      consideration as adjuvant therapies.

PMID- 9782975
TI  - Patients' views of interferon therapy in MS.
AB  - Interferon beta-1b is a new and somewhat controversial drug therapy used in the
      management of MS. In this study people using interferon beta-1b reported fewer
      relapses, less use of their primary health-care services and an overall
      improvement in their condition. Outcome measures for use in MS need to be more
      sensitive in order to measure effectively the impact of therapies such as
      interferon beta-1b and beta-1a. Further research using validated quality-of-life
      scales to fully assess the impact of these new treatments is urgently needed.

PMID- 9782976
TI  - Complaints procedure.
AB  - Many complaints by patients can be dealt with at ward level through discussion
      and an apology but others are more serious. All hospitals must have a complaints
      procedure in place and nurses must be aware of the steps complaints can take.

PMID- 9782977
TI  - The nutritional response to trauma in older people.
AB  - Physiological changes affecting the digestive system in old age may mean that
      older people have a higher risk of malnutrition as a result of physical trauma.
      The findings showed that the nutritional status of older subjects who had
      undergone total hip replacement did not correlate with age. The study indicated
      that people over the age of 75 may have a tendency of develop postoperative
      complications, which could be affected by malnutrition.

PMID- 9782978
TI  - Erectile dysfunction.

PMID- 9782979
TI  - Physiological ageing: 2.

PMID- 9782980
TI  - Prostate surgery: a communication challenge.
AB  - Many patients requiring prostate surgery experience a lack of interest from
      health-care staff in relation to their views and opinions. Information offered to
      patients who have undergone prostate surgery is often inadequate as a result of
      poor communication by health staff. Nurses need to understand the priorities of
      their patients and use this information to inform the way in which advice is
      given.

PMID- 9782981
TI  - Infusion pumps.
AB  - Infusion pumps are used to deliver drugs and other substances to patients at a
      pre-set rate. Infusion pumps are classified according to their application,
      whether ambulatory, patient controlled, anaesthesia or general purpose units.

PMID- 9782982
TI  - Venous leg ulcers. Part 2: Assessment.
AB  - The assessment of a patient with a leg ulcer is a complex process. As well as the
      ability to perform such tasks as Doppler ultrasound and ABPI measurements, nurses
      must be aware of factors that will delay healing or increase the likelihood of
      ulcer recurrence.

PMID- 9782983
TI  - Children's nursing.

PMID- 9782984
TI  - Essential skills in research.

PMID- 9782985
TI  - Be prepared to beat stress.

PMID- 9782986
TI  - Wound swabbing techniques.

PMID- 9782987
TI  - Workplace stress: a hospital team approach.
AB  - Critical incident stress can adversely affect individuals both at work and at
      home. Debriefing offers a safe environment in which they can express their
      emotions. Stress management teams can benefit both staff and employers.

PMID- 9782988
TI  - Reducing pressure sores after hip fractures.
AB  - Pressure sore prevention is a challenging aspect of caring for elderly patients
      who have sustained femoral neck fractures. Despite implementation of a pressure
      sore prevention policy, a small-scale audit revealed that almost half of patients
      who sustained femoral neck fractures developed Stage 1 or Stage 2 pressure sores
      while in hospital. The findings indicate the need for more proactive pressure
      sore prevention in A&E and theatres.

PMID- 9782989
TI  - The value of quantitative research in nursing.
AB  - Quantitative research is an objective process used to obtain numerical data. The
      form of quantitative research used is influenced by current knowledge of the
      problem. Careful planning in the design stage is essential when undertaking
      quantitative research.

PMID- 9782990
TI  - Wound infection and wound swabbing.
AB  - There is a significant lack of knowledge in relation to the identification and
      management of infected wounds. More attention should be given in nurse education
      to knowing when and how to obtain would swabs. Wound swabbing practices should be
      standardised.

PMID- 9782992
TI  - Home blood glucose monitoring.

PMID- 9782991
TI  - Detecting delirium in hospitalised older people.
AB  - Delirium in older people is associated with increased mortality. Delirium often
      goes unrecognised by health-care staff. Routine measurement of mental status in
      older people is an important nursing intervention.

PMID- 9782993
TI  - Chronic obstructive pulmonary disease.

PMID- 9782994
TI  - Temperature measurement devices.
AB  - Nurses should gain an understanding of the physiological mechanisms involved in
      thermoregulation and be aware of the many variables that affect temperature
      measurement. The rectum, mouth, axilla and tympanic membrane may be used for
      temperature measurement. To ensure accurate readings, measurements for each
      individual should be obtained in a consistent manner.

PMID- 9782996
TI  - Venous leg ulcers. Part 4: Wound care.
AB  - When assessing a leg ulcer the nurse should note the size and site of the wound,
      any exudate present and the presence of pain and allergies. A suitable wound
      dressing can then be selected.

PMID- 9782995
TI  - Breast cancer. Part 2: Management.
AB  - Management of breast cancer will depend on its stage and degree of spread.
      Management may be by surgery, chemotherapy, endocrine therapy or radiotherapy, or
      a combination of some or all of these.

PMID- 9782997
TI  - Nursing older people.

PMID- 9782998
TI  - More publicity.

PMID- 9782999
TI  - A nurse has failed to meet certain professional standards.

PMID- 9783001
TI  - These novel strategies decrease ED delays.

PMID- 9783000
TI  - Best care for the dying: listen to their needs.

PMID- 9783002
TI  - A clinical look at body piercing.

PMID- 9783004
TI  - New treatment options for stress incontinence.

PMID- 9783003
TI  - What's wrong with this patient? Hemochromatosis.

PMID- 9783006
TI  - On-scene care.

PMID- 9783007
TI  - ED triage.

PMID- 9783005
TI  - Nurses go underground.

PMID- 9783008
TI  - Check your paycheck!

PMID- 9783009
TI  - Older adults need more vitamin B12.

PMID- 9783010
TI  - On being an advocate.

PMID- 9783011
TI  - [Nursing care. An essential part of the problems of nursing. Interview by
      Patricia Jaffrey].

PMID- 9783012
TI  - [Nursing care. The evolution of nursing classification].

PMID- 9783013
TI  - [Nursing diagnosis, a tool for service to the patient].

PMID- 9783014
TI  - [Anxiety, fear, anguish....].

PMID- 9783015
TI  - [Nursing diagnosis in people in precarious situations].

PMID- 9783016
TI  - [Ending the silence, part of a nurse's work].

PMID- 9783017
TI  - [Quality, accreditation. Neighborhood hospitals, transforming or dying].

PMID- 9783018
TI  - [Health economics. Offers of care and health professionals].

PMID- 9783019
TI  - [To know better the dangers of oxygen bottles].

PMID- 9783020
TI  - [Preventing the risks of biological fluids].

PMID- 9783021
TI  - [Commentary by Emmanuelle Girou. An excellent tool for the education of health
      personnel].

PMID- 9783022
TI  - [Elimination of drugs. Elimination half-life of a drug].

PMID- 9783023
TI  - [Patient care records. 2. Access].

PMID- 9783024
TI  - [How to deal with abnormal behavior. Clinical case].

PMID- 9783025
TI  - [Pain].

PMID- 9783026
TI  - [Cardiac insufficiency. Essential clinical facts].

PMID- 9783027
TI  - Tobacco.

PMID- 9783028
TI  - Smoking among males in a low socioeconomic area of Karachi.
AB  - Approximately half of the families in Pakistan reported having at least one
      smoker in 1992. Smokers were less educated, poorer and more likely to come from a
      rural background than non-smokers. The proportion of family earnings in poor
      families with marginal incomes, may be substantial. We conducted this survey to
      determine the prevalence of cigarette smoking in males over 15 years of age in
      Azam Basti, an urban squatter settlement of Karachi where 31% of the children
      less than 5 years old were malnourished. A pretested, structured questionnaire
      was administered to males aged fifteen years and above, from randomly selected
      homes in Azam Basti. In our sample of 102 persons the respondents were 38 years
      old on average, and earned about Rs. 4,500 (US $130) per month. Persons with 10
      or more years of education were thrice as likely to have never smoked as compared
      to those with less than ten years of schooling, (OR = 3.6, 95% confidence
      interval 1.2, 11.4). Current smokers were more than twice as likely as non
      smokers to have monthly household incomes less than Rs. 5000 (US $140) (OR = 2.4,
      95% confidence interval 0.8, 7.3). Smoking is common in urban squatter
      settlements in Pakistan. Parental smoking and its relationship with malnutrition
      in children under five is not well documented or publicized, even though there is
      evidence that it has a contribution. We propose that primary health care programs
      consider smoking prevention and cessation as community based interventions.

PMID- 9783029
TI  - Prevalence and pattern of smoking in Pakistan.
AB  - OBJECTIVE: To determine the prevalence and pattern of smoking amongst Pakistanis.
      SAMPLING DESIGN: A two stage stratified sample design was adopted for the survey,
      Primary Sampling Units (PSU's) and Secondary Sampling Units (SSU's). SETTING:
      Urban and Rural, Pakistan 1990-94. SUBJECTS: Stratified systematic sample of 9441
      males and females aged 15 years and above. MAIN OUTCOME MEASURES: Smokers were
      defined as, subjects who were currently smoking and who had smoked > or = 100
      cigarettes/beedis or chillum/huqqa in their life time. RESULTS: In Pakistan 21.6%
      (36% males and 9% females) of 9441 subjects were smokers. In urban areas it was
      20.7% and in rural 22.0%, males were predominant in both urban and rural areas.
      Proportion of smokers who used cigarette/beedi were significantly higher in males
      (60%) while chillum/huqqa were more in females (62%). Prevalence increased with
      age upto 64 years, after which it declined but in urban females it continued to
      rise with age. Among both males and females; illiterate, married individuals with
      poor general health were more likely to smoke. These factors were 2 to 3 times
      more in males and 2 to 5 times more in females who were more likely to be smokers
      than those who were literate, single individuals with good general health.
      CONCLUSION: Smoking was more prevalent in illiterate, married persons and those
      with poor general health.

PMID- 9783030
TI  - Predicting prognosis in lung cancer: use of proliferation marker, Ki67 monoclonal
      antibody.
AB  - An investigation was carried out to assess the prognostic significance of
      proliferation marker Ki67 in a group of lung cancer patients treated by surgery
      (limited disease). Tissue was not available for Ki67 immunostaining in inoperable
      group. The diagnosis is established by bronchial biopsy which does not carry
      enough tissue for frozen section and counting. This study is supplemented by
      estimating the prognostic significance of histological sub-types in the operable
      group and in a group of inoperable patients with extensive disease. These are
      usually treated by radiotherapy and/or chemotherapy. In all, 267 patients were
      studied including 105 treated by surgery. These patients attended King's College
      and Brompton Hospital, UK, between 1986 and 1989. With regard to proliferation
      marker Ki67 done for the surgical group, only patients with Ki67 scores of less
      than 5% did survive significantly longer than the rest. Histology did not make
      any significant contribution in determining prognosis in both operable and
      inoperable groups. Although follow-up is limited (mean 20 months), Ki67 antibody
      seems promising in identifying low and high grade disease in the initial stage of
      lung cancer. It may prove useful for category of patients with high scores to be
      placed on chemotherapy/radiotherapy. Results suggest that in the case of lung
      tumour, proliferative activity is a better prognostic indicator than histological
      type.

PMID- 9783031
TI  - Primary myelodysplastic syndrome: clinical spectrum of 53 cases.
AB  - Fifty three (45 males, 8 females) patients with primary meylodysplastic syndrome
      were seen between January 1990 and June, 1996. Fifteen (28%) patients had
      refractory anaemia (RA), 9 (17%) refractory anaemia with ring sideroblast (RARS),
      21 (40%) refractory anaemia with excess blasts (RAEB), 5 (9%) refractory anaemia
      with excess blasts in transformation (REABt) and 3 (6%) had chronic
      myelomonocytic leukemia (CMML). The mean age for the whole cohort was 59 years.
      Patients with RAEB and RAEBt were significantly younger than other FAB types with
      a mean age of 53.5 and 45 years respectively. Among the FAB types RAEB appeared
      to be over represented. Symptomatic anaemia (66% cases) was the major cause to
      seek medical attention. The commonest laboratory findings was anaemia; Hb < 8
      g/dl in 31 (59%) patients. Only two patients had Hb > 12 g/dl at presentation.
      Twenty four (45%) patients had normocytic anaemia, mainly in RAEB group (61%).
      Macrocytosis was a dominant finding in patients with RA (53%) and RARS (53%).
      Bicytopenia (72%) was a more common finding than pancytopenia (8%). Bone marrow
      was normocellular in 32 (60%) patients and hypoplastic in 11 (21%).
      Dyserythropoiesis predominantly affected RA (80%), RARS (55%) and RAEB (43%)
      groups. Bilineage dysplasia (21%) was commoner than trilineage dysplasia (19%).
      Increased bone marrow fibrosis was seen in about half of the available trephines,
      mainly in RAEB patients. Median survival of patients was ten months with a follow
      up duration of 2-55 months. Four patients transformed to acute leukemia (M1 or
      M2) and died subsequently. However, infection was major complication and cause of
      death (10 cases). The preponderance of younger people to acquire the disease
      (especially the RAEB and RAEBt variants), the emergence of RAEB as the major
      group of MDS and increased prevalence of hypoplastic MDS point towards non
      therapeutic genotoxin (s) in the causation of disease. Shortened survival and low
      rate of acute transformation points that patients did not withstand cytopenias
      and died earlier.

PMID- 9783032
TI  - Prescribing practices: an overview of three teaching hospitals in Pakistan.
AB  - The extent and nature of irrational prescribing of drugs has not been explored in
      Pakistan A pilot study was therefore undertaken in three major teaching hospitals
      located in the twin cities of Rawalpindi/Islamabad. Six hundred and one
      prescriptions from medical, paediatrics and psychiatry units of these hospitals
      were analyzed to study the prescribing pattern. The mean number of drugs per
      prescription was found to be 2.97. Only 23.6% drugs were prescribed by their
      generic names. About 80% of the prescribed drugs were from the National Essential
      Drug List of Pakistan. Use of injectable preparations was 17.1%. Antimicrobials
      constituted 20.4% of the drugs prescribed, frequently for cases of acute
      respiratory infections and gastroenteritis. The average cost of treatment per day
      was Rupees 26.10 in the outdoors and Rs. 88.36 in indoors. Treatment did not
      correlate to the diagnosis in 24.6% of the cases. Doses of drugs were
      inappropriate in 30.6% prescriptions. Duration of treatment was not specified on
      a vast majority (73.4%) of the prescriptions. The data highlights the need for
      educational, managerial and regulatory interventions to rationalize the drug use
      in Pakistan.

PMID- 9783033
TI  - Smoking in Pakistan: more than cancer and heart disease.

PMID- 9783034
TI  - A comparative review of two screening instruments: the Aga Khan University
      Anxiety and Depression Scale and the self reporting questionnaire.

PMID- 9783035
TI  - Single stage reconstruction of the amputated penis using a microsurgical radial
      forearm flap transfer.

PMID- 9783036
TI  - Information technology and health care.

PMID- 9783038
TI  - Prevalence of hepatitis B, C and HIV virus infection among beta thalassaemia
      major patients.

PMID- 9783039
TI  - Childhood tuberculosis.

PMID- 9783040
TI  - Neonatal tetanus--a killer disease that is totally preventable.

PMID- 9783041
TI  - Epidemiology of childhood tuberculosis in a hospital setting.
AB  - Two hundred paediatric cases of tuberculosis were studied over two years. The
      children usually presented with fever, cough, weight loss or failure to thrive
      and pallor. The diagnosis was based on history, clinical examination, chest and
      other relevant radiographs, Mantoux test, erythrocyte sedimentation rate (ESR)
      and where necessary cerebrospinal, pleural and ascitic fluid examinations and
      lymph gland histopathology were done. The most commonly affected age group was
      between 2-5 years and pulmonary tuberculosis was the most frequent diagnosis
      followed by tuberculous adentitis.

PMID- 9783042
TI  - A review of 207 newborn with tetanus.
AB  - In this study, 207 patients with neonatal tetanus admitted to Erciyes University,
      Faculty of Medicine, Unit of Neonatology between 1976 and 1994 were investigated
      retrospectively. One hundred and sixty-seven (80.6%) patients had non-hygienic
      home deliveries and none of the mothers of the children had been immunised with
      tetanus toxoid. Of the 207 patients, 161 (77.8%) were males, 46 (22.2%) were
      females. Failure to suck and twitching were the most frequent symptoms. The mean
      age of patients who died or survived was 6.9 and 8.8 days respectively (p >
      0.05). Mean birth weight was 3092 g for the fatal cases and 3317 g for the
      survivors (p < 0.05). Mean age of onset of symptoms was 5.5 days for the fatal
      cases and 6.5 days for the survivors (p < 0.05). Mean period between onset of
      symptoms and hospital admission was 1.5 days for the fatal cases and 2.1 days for
      the survivors (p > 0.05). Ninety-seven (46.8%) of the 207 patients died. Mean age
      of death was 9.3 days and most of the patients died at the fifth day of admission
      to hospital. Sex, age on admission and duration of symptoms did not affect the
      prognosis. In addition, the efficacy of the diazepam, phenobarbital sodium and
      chlorpromazine used for sedation in neonatal tetanus was investigated. Of 207
      patients, 43 patients were treated with diazepam, 33 patients with phenobarbital
      sodium, another 33 patients with phenobarbital sodium + chlorpromazine and 94
      patients were treated with diazepam + phenobarbital sodium +/- chlorpromazine
      called as "combined therapy". The least mortality rate was found in the group
      treated with "combined therapy" and the highest mortality rate in the group
      treated with phenobarbital sodium + chlorpromazine (p < 0.001). The most frequent
      cause of death was apnea in the first week and sepsis in the later period.

PMID- 9783043
TI  - Chloroquine resistant malaria in children.
AB  - Malaria remains a major cause of childhood morbidity and mortality. The changing
      susceptibility of Malaria parasites to drugs means that it is no longer possible
      to make global generalization about its chemotherapy. This study was conducted in
      District Hospital, Mirpurkhas, Sindh. Over sixteen months period four hundred and
      six patients had slide documented malarial parasites. Sixty-five percent had
      plasmodium falciparum, 33% plasmodium vivax and 2% had both. Approximately, 81%
      responded to chloroquine while 19% were non-responders. Chloroquine non
      responders were treated with halofantrine or sulfadoxine--pyrimethamine
      combination. P. falciparum being the dominant species and its emergence of
      resistance to Chloroquine, in life threatening and serious forms of malaria
      should be treated with parenteral quinine. Antimalarials other than Chloroquine
      should be reserved for non-responders. Therefore, rational use of drugs is
      essential.

PMID- 9783044
TI  - Haemolytic uraemic syndrome in childhood: an experience of 7 years at the Aga
      Khan University.
AB  - We reviewed the case records of all children admitted to the Aga Khan University
      Hospital (AKUH) with a diagnosis of Haemolytic Uremic Syndrome (HUS) over a 7
      year period (July, 1988-June, 1995). A total of 33 patients were admitted to the
      Pediatric ward at (AKUH) with a median age of 16 months (range 4 months-9 years).
      97% cases identified were of the classic variety and no familial case was
      identified. The mean duration of illness was 27 days, 39% had an illness > 28
      days. Diarrhoea and prior antibiotic used was in 97% patients. Oliguria at
      admission was seen in 52.5% and seizures in 24% of cases. Thrombocytopenia,
      anemia and leucocytosis at admission was present in > 72% of children.
      Hyponatremia was present in 42% while acidosis, hypocalcemia and hyperkalemia was
      seen in 30% of children. Despite optimal management and peritoneal dialysis in 14
      (42%) patients, 8 (24%) died. No specific relationship was found between
      mortality and any clinical or laboratory feature at presentation. Our data
      highlights the importance of HUS in the Pediatric age group and the need for
      further studies to delineate risk factors for adverse outcome.

PMID- 9783045
TI  - Determination of skeletal age in children aged 8-18 years.
AB  - Skeletal age determination exercise was performed by Greulich-Pyle method in 402
      normal children (219 males and 183 females) aged 8-18 years during 1993-94 at
      Chandka Medical College, Larkana. On the average, the males were 1 year and the
      females were 0.5 years retarded from 8-15 years and from 8-13 years respectively.
      This retardation during childhood might be due to malnutrition, ill health or
      other environmental factors. However, males after 15 years and females after 13
      years (round about puberty and afterwards) were found advanced in their skeletal
      age indicating earlier maturity in our children as compared to western children.

PMID- 9783046
TI  - A comparative study of cefixime and chloramphenicol in children with typhoid
      fever.
AB  - We compared cefixime with chloramphenicol in a randomized trial for treatment of
      children with culture positive typhoid fever. Twenty children were given cefixime
      10 mg/kg/day orally and twenty received chloramphenicol 50 mg/kg/day orally. On
      entry in the study, the clinical characteristics of the two groups were
      comparable. Duration of therapy was 14 days. Clinical cure was observed in 18
      (90%) patients treated with cefixime and 9 (45%) treated with chloramphenical.
      Out of the 11 patients who did not respond to chloramphenicol, 10 were switched
      over to cefixime and all of them were cured. Over all 28 cases out of 30 (93.3%)
      P = 0.0049 were cured by cefixime.

PMID- 9783047
TI  - An hourglass type of intrathoracic lipoblastoma manifested by edema in right
      upper limb.

PMID- 9783048
TI  - Adrenoleukodystrophy: case report.

PMID- 9783050
TI  - To re-emphasize the need for fluoride in blood samples for glucose-level testing.
AB  - Blood samples were collected from 30 subjects. To a portion from each sample was
      added Fluoride/Ethylene Diamine Tetra Acetate (E.D.T.A) to inhibit glycolysis and
      clotting. The remaining portions were allowed to clot without any inhibitor. On
      subjecting to glucose concentration testing, the portions without the inhibitor
      showed a decline in the glucose level of 8 mg/dl (0.44 mmol/l) in the first hour
      and of 7 mg/dl (0.39 mmol/l) per hour in the next two hours. It is re-emphasised
      that a glycolysis inhibitor should always be added to blood samples drawn for
      glucose level testing. Otherwise, the reported results could be misleading.

PMID- 9783053
TI  - Endometrial ossification.

PMID- 9783051
TI  - A study of the accuracy of the Precision Q.I.D. glucometer.
AB  - The Precision Quantum-in-dium (Q.I.D.) Glucometer was used to determine the
      glucose concentrations of 38 human blood samples. The same samples were also run
      on the OPERA Chemistry Autoanalyzer 2010 system. More than 44% of the glucometer
      reports had a difference of greater than 15% from the respective autoanalyzer
      reports. The calibration of the glucometer could be the source of the error and
      an improvement is recommended.

PMID- 9783054
TI  - A non-invasive method for bladder electromyography in humans.
AB  - No convincing correlation of bladder EMG in humans to simultaneously measured
      intravesical pressure has been reported in the literature. In most studies on
      bladder EMG the electrodes contact the bladder wall itself. This causes problems
      in the discrimination between very small extracellular signals, reflecting actual
      membrane potential changes of bladder muscle cells, and large electro-mechanical
      artefact caused by electrode movement as the tissue contracts. Aim of this study
      is to investigate whether bladder EMG can be performed non-invasively with Ag
      AgCl surface electrodes that are placed on the abdominal skin of healthy
      volunteers. Bipolar electrode signals are obtained in a diagonal, vertical and
      horizontal direction of the abdominal electrodes. A conventional urodynamic
      investigation is performed according to International Continence Society
      standards simultaneously with bladder EMG. This new method shows that voiding is
      accompanied by a slow voltage change in bipolar electrode signals. The
      contribution of abdominal and other striated muscle activity to the bipolar
      electrode signals can clearly be distinguished from the slow voltage changes
      related to voiding. Free flowmetry shows that the electrical activity picked up
      by the abdominal electrodes is related to bladder emptying. In pressure/flow
      studies a relation between the electrical activity and the detrusor pressure is
      found. The present results suggest that the slow voltage changes found during
      bladder contraction are caused by summed membrane potential changes of bladder
      muscle cells, but this concept needs further testing. Also, validation for
      clinical use remains to be established.

PMID- 9783055
TI  - Role of the plasma and erythrocytes in veno-arterial portal changes during post
      prandial state in the rat.
AB  - The determination of plasma and whole blood free amino acid concentrations in
      arterial and portal venous blood during post prandial state in the rat was used
      to estimate the role of the erythrocytes in amino acid exchanges. The erythrocyte
      contents were calculated from plasma, whole blood concentrations and the
      hematocrit. The veno-arterial concentration differences in plasma were
      significant for all amino acids except a-aminobutyrate and ornithine whereas in
      the erythrocytes only 8 amino acids exhibit significant differences (ASP, ALA,
      VAL, MET, ILE, LEU, TYR, PHE). For 6 amino acids, a significant correlation
      between the plasma and the erythrocyte concentration has been found (VAL, ILE,
      LEU, TYR, PHE, HIS). These data suggest that in vivo during the time of contact
      between blood and organ tissues, some amino acids but not all are significantly
      taken up by the erythrocytes. Thus, it may be concluded that erythrocyte amino
      acid blood transport in arterio-venous portal exchanges, concerns particularly
      tyrosine and essential amino acids. The erythrocyte amino acid transport
      represents quantitatively about 20 per cent of the total blood transport.

PMID- 9783056
TI  - Red blood cell osmotic fragility in Bufo arenarum exposed to lead.
AB  - The effects on red blood cells of a single sublethal dose of Pb of 100 mg kg-1
      administrated to adult Bufo arenarum were studied. The blood d-aminolevulinic
      acid dehydratase (d-ALAD) activity, the red blood cell (RBC) osmotic fragility
      (OF), and the hematocrit (Hct) were measured in control and lead poisoned toad.
      The enzyme d-ALAD is considered as a specific biomarker for human and animals
      lead exposure. In Bufo, lead also provoked a significant decrease in the d-ALAD
      activity without changes in the Hct. OF test was used to compare the impact of Pb
      on the extent of the RBC hemolysis produced by osmotic stress. Experimental data
      (absorbance of solubilized hemoglobin and [NaCl]) were fitted to the Orcutt et
      al. equation (1995) that allows a precise characterization of the parameters
      involved in OF. In blood from injected toads, the OF resulted significantly
      reduced. These changes were interpreted as a consequence of alterations in the
      composition and conformation of the RBC membrane due to Pb, as it was described
      for human erythrocytes.

PMID- 9783057
TI  - The fate of plasma kallikrein in normal and kininogen-deficient rats.
AB  - The clearance of exogenous plasma kallikrein, its uptake by liver, spleen,
      kidneys, lungs and its extravasation in the paws were determined in normal Wistar
      rats, normal and kininogen-deficient Brown Norway rats. Kallikrein was purified
      from rat plasma and labelled with 125I. After intravenous injection of 125I
      kallikrein, the disappearance of acid-precipitable kallikrein from the blood fits
      a biexponential curve similar in the three groups of rats: a rapid initial
      clearance (T1/2 around 3 min) followed by a phase of slower elimination (T1/2
      around 50 min). Removal of kallikrein from the blood was associated with a large
      uptake of radioactivity by the liver: 67% of the 125I-kallikrein cleared from the
      blood at 10 min. The kidneys and the spleen accumulated small amounts of the
      radioactivity. The uptake of kallikrein by the spleen was slightly reduced in
      kininogen-deficient rats. The kininogen deficiency in Brown Norway rats from the
      strain BN/May Pfd was confirmed by the low levels of kinins released by tissue
      kallikrein and by a prolongation of activated thromboplastin times in the plasma
      of these animals. We concluded that plasma kallikrein is rapidly cleared from the
      circulation of the rat. The liver is the main clearing organ of plasma
      kallikrein. The disappearance of kallikrein from the circulation is not affected
      by the lack of high molecular weight kininogen, except in the case of the uptake
      of the enzyme performed by the cells of the spleen, which is reduced.

PMID- 9783058
TI  - Fatty acid profiles and non enzymatic lipid peroxidation of microsomes and
      mitochondria from bovine liver, kidney, lung and heart.
AB  - The light emission = chemiluminescence and fatty acid composition, two markers of
      lipid peroxidation process, was evaluated in bovine liver, kidney, lung and heart
      microsomes and mitochondria incubated in the presence of ascorbate-Fe2+ at 37
      degrees C. Microsomal and mitochondrial fractions obtained from lung, kidney and
      heart were more resistant to lipid peroxidation than those isolated from the
      liver. The ascorbate-Fe2+ seemed to be totally ineffective in stimulating
      peroxidation of bovine lung, heart and kidney microsomes or mitochondria. Whereas
      bovine liver microsomes or mitochondria displayed the highest values of
      chemiluminescence when incubated in the presence of ascorbate-Fe2+. The
      peroxidizability index a parameter that indicate the maximal rate of oxidation of
      specific fatty acids showed statistically significant differences in mitochondria
      isolated from lung heart and kidney and microsomes isolated from lung. The fatty
      acid profile of the subcellular fractions obtained from those tissues do not
      appear to be responsible for their different susceptibility to free radical
      degradation. Other factor/s may be responsible for the protection to lipid
      peroxidation observed in microsomal or mitochondrial fractions obtained from
      bovine lung, heart and kidney.

PMID- 9783059
TI  - High level runners are able to maintain a VO2 steady-state below VO2max in an all
      out run over their critical velocity.
AB  - During prolonged and intense running exercises beyond the critical power level, a
      VO2 slow component elevates VO2 above predicted VO2-work rates calculated from
      exercise performed at intensities below the lactate threshold. In such cases, the
      actual VO2 value will increase over time until it reaches VO2max. The aims of the
      present study were to examine whether the VO2 slow component is a major
      determinant of VO2 over time when running at a speed beyond critical velocity,
      and whether the exhaustion latency period at such intensity correlates with the
      magnitude of the VO2 slow component. Fourteen highly trained long-distance
      runners performed four exhaustive runs, each separated by one week of light
      training. VO2 and the velocity at VO2max (vVO2max) were determined for each by a
      graded treadmill exercise. The critical velocity (86.1 +/- 1.5% vVO2max) of each
      runner was calculated from exhaustive treadmill runs at 90, 100 and 105% of
      vVO2max. During supra-critical velocity runs at 90% of vVO2max, there was no
      significant rise in VO2max (20.9 +/- 2.1 ml min-1 kg-1 between the third and last
      min of tlim 90), such that the runners reached a VO2 steady-state, but did not
      reach their vVO2max level over time (69.5 +/- 5.0 vs 74.9 +/- 3.0 ml min-1 kg-1).
      Thus, subjects' time to exhaustion at 90% of vVO2max was not correlated with the
      VO2max slow component (r = 0.11, P = 0.69), but significantly correlated with the
      lactate threshold (r = 0.54, P = 0.04) and the critical velocity (% vVO2max; r =
      0.65, P = 0.01). In conclusion, the present study demonstrates that for highly
      trained long-distance runners performing exhaustive, supra-critical velocity runs
      at 90% of vVO2max, there was not a VO2 slow component tardily completing the rise
      of VO2. Instead, runners will maintain a VO2 steady-state below VO2max, such that
      the time to exhaustion at 90% of vVO2max for these runners is positively
      correlated with the critical velocity expressed as % of vVO2max.

PMID- 9783060
TI  - Comparison between the natural postnatal maturation and the spermine-induced
      maturation of the rat intestine.
AB  - In the suckling rats, orally provided spermine induced structural and biochemical
      changes in the intestine, which are characteristics of the postnatal maturation.
      This induced maturation was compared to that occurring spontaneously. Eight mumol
      spermine were administered orally once a day, for one or three days, to suckling
      rats which were 11 days old at the beginning of the experiment. The animals were
      killed 0, 2, 4, 6, 8, 10 hours or 3 days after the first treatment. Control rats
      from the same litter were treated in the same way but received only the vehicle.
      In order to complete the study of the naturally occurring maturation, another
      group of rats was killed when they were 12, 13, 15, 16, 17, 18, 19, 20, 21 or 30
      days old. Animal and intestine weights were measured. Disaccharidase specific
      activity, and protein, DNA and RNA contents were estimated in the small
      intestine. Histological and ultrastructural aspects of the intestinal mucosa were
      examined. For all these parameters, the maturation induced by spermine ingestion
      appeared close to that occurring naturally at weaning. Consequently, dietary
      spermine induces all the morphological and biochemical modifications
      characterizing the intestinal postnatal maturation in the suckling rat suggesting
      a role of the polyamines in the naturally occurring processes.

PMID- 9783061
TI  - Effect of thymosin fraction five (TF5) on early neuroembryogenesis in the newt
      Triturus cristatus.
AB  - Thymosin fraction five (TF5), a well-characterized immunoregulatory thymic
      preparation, has been reported to stimulate corticotropin (ACTH) release. The
      present study explores the morphogenetic role of TF5 on early stages of nerve
      tissue formation during embryogenesis. In vivo TF5-treatment of newt embryos
      during neurulation results in stimulation of the process expressed at a macro
      microscopical level by emphasizing the embryo's relief and by accelerating the
      neural tube closure. The stimulating effect of TF5 on neurulation is manifested
      ultrastructurally by enhanced apical endocytosis, a well-developed contractile
      microfilamentous layer, increased apical intercellular junctions and changes of
      the cytoplasmic organelles linked with the protein synthesis. The polymorphism of
      mitochondria and the morphological expression of enhanced yolk material
      assimilation confirm the idea of TF5-stimulating effect on the neuroepithelial
      cells.

PMID- 9783062
TI  - [Biophysical mechanisms of the erythrocyte sedimentation reaction].
AB  - Is shown, that the process of red blood sedimentation under the conditions of
      standard measurement of a clinical parameter ESR (erythrocyte sedimentation rate)
      is multistage and non-monotonous. Red blood sedimentation is preceded by the
      "latent" period lasting up to tens of minutes. When sedimentation begins,
      multiple accelerations and decelerations in the movement of the boundary between
      red blood and clean plasma are observed. The differences in dynamics of red blood
      sedimentation (DRBS) of healthy donors and patients with sharp myocardial
      infarction are revealed. The form of DRBS diagrams depends upon metabolic
      activity of blood. We suggest that DRBS represents the active reaction of blood,
      as of an integral surviving tissue, on stress factors acting on it under the
      conditions of ESR determination.

PMID- 9783063
TI  - [Physiologic activation of peroxidation by negative air ions].
AB  - The effect of negative air ions (NAI) was investigated on physiological processes
      of peroxidative oxidation in mitochondria preserving their native structure
      organization in associations in rat liver homogenate. Tchijevsky lustre
      generating superoxide was served as a source of NAI. The investigated objects
      were put into solutions pretreated with NAI flow. An increase of peroxide induced
      Ca2+ release from mitochondria loaded with the cation was found. Under prolonged
      action of NAI flow on homogenates kept in ice followed by incubation in media
      pretreated with NAI an elevation of products of peroxide lipid oxidation (POL)
      was found in case of their low initial level and decrease of POL products in case
      of their high initial level. The range of changes is considerably less than under
      pathogeneous rise of POL. The discovered mild activation of peroxidative
      oxidation within physiological range of POL concentrations is considered as a
      primary physico-chemical mechanism of beneficial biological action of NAI.

PMID- 9783064
TI  - [Electromagnetic bioengineering].
AB  - The results of experimental and theoretical studies on the combined action of
      weak electrical as well as constant and variable low-frequently magnetic fields
      on physicochemical and biological systems are generalised. It is shown that weak
      magnetic fields with parameters close to characteristics of the geomagnetic field
      exert selective effects, initiating the processes of chemical reactivity and ion
      conductivity in aqueous solutions of organic molecules.

PMID- 9783065
TI  - [Change in the infradian rhythms of some physiological processes, controlled by
      the epiphysis, in epiphysectomized rats exposed to a super low frequency variable
      magnetic field].
AB  - The infradian rhythmic of the behavioral parameters, urination, body mass and
      temperature in epiphysectomized rats exposed to a variable magnetic field of a
      frequency of 8 Hz and induction of 5 microT influence was studied. It was found
      that the removal of epiphysis leads to the reorganization of power spectra of
      biorhythms, a rise of their amplitudes, and the development of desynchronosis.
      Further exposure of epiphysectomized rats to a variable magnetic field partially
      normalizes the amplitude-phase relations and decrease the disbalance of the
      processes. These data indicate the important role of epiphysis in the
      magnetoreception and formation of the temporal structure of the organism and
      suggest the existence of other structures sensitive to variable magnetic field.

PMID- 9783066
TI  - [Correlation of fluctuations in the activity of the rat monooxygenase system with
      dynamics of tidal gravitational changes].
AB  - Semi-annual changes in monthly average levels of functioning of the rat liver
      monooxygenase system in norm (the amidopyrine test) were found. It was shown that
      there are inverse linear correlations between the level of demethylation and
      acetylation of amidopyrine and the semi-annual periodicity of average monthly
      data on the acceleration of tide changes in gravity.

PMID- 9783067
TI  - [Properties of the catalytic center of a secretory 28kDa protein (1-cys
      peroxiredoxin) from rat olfactory epithelium].
AB  - The secretory 28 kD protein, an abundant water-soluble protein from rat olfactory
      epithelium, belongs to the 1-Cys subfamily of thiol-specific antioxidants
      (peroxiredoxins). The 28 kD protein contains a single cysteine residue at the
      position 46 which accounts for the antioxidant activity. Here we studied the
      effects of N-ethyilmaleimide and t-butyl hydroperoxide on the antioxidant
      activity of the 28 kD protein and that of the 23 kD protein from rat erythrocyte
      which is a member of 2-Cys subfamily of peroxiredoxines. N-ethylmaleimide,
      modifier for cysteine residues, had no effect on antioxidant activity of the
      dithiothreitol-treated 28 kD protein but irreversibly inhibited activity of the
      23 kD protein under reducing conditions. The 28 kD protein was sensitive to
      treatment with peroxides: t-butyl hydroperoxide at micromolar concentrations was
      shown to irreversibly inactivate 28 kD protein. In the presence of
      dithiothreitol, the lower level of peroxide concentrations was required to
      inhibit 28 kD protein activity. The mechanism of this effect may be mediated
      through conversion of sulfhydryl group of 46Cys to oxidized states (46Cys-SO2H
      and 46Cys-SO3H). Antioxidant property of 23 kD protein was impaired by t-butyl
      hydroperoxide only in the presence of dithiothreitol. The concentrations of t
      butyl hydroperoxide needed to affect the 23 kD protein were at least one order of
      magnitude higher than were required for the 28 kD protein inhibition. The given
      results suggest the essential differences between catalytic site of 28 kD protein
      and that of 2-Cys peroxiredoxins.

PMID- 9783068
TI  - [Effect of geomagnetic disturbances on the blood coagulation system in patients
      with ischemic heart disease and prospects for correction with medication].
AB  - The goals of this investigation were to study the influence of geomagnetic
      activity on platelet aggregation, blood coagulation in venous blood. The
      geophysical information was provided by the Institute of Terrestrial Magnetism,
      Ionosphere and Radio Waves Propagation Russian Academy of Sciences. The most
      significant changes were obtained in increased platelets aggregation, blood
      coagulation during increased geomagnetic activity. All these effects may cause
      the development of angina pectoris. The using of acetyl acetylsalicylic enable
      decreased the negative effect of geomagnetic disturbances on patients with
      ischemic heart disease.

PMID- 9783069
TI  - [Myocardial infarct and geomagnetic disturbances: analysis of data on morbidity
      and mortality].
AB  - Relationships between different parameters of the geomagnetic activity and
      medical statistical data on myocardial infarction were investigated anew, because
      previous results in this field have been often inconsistent. The data are daily
      numbers of myocardial infarction incidence rates (15,543 cases) and number of
      deaths for infarction (3,065 cases), abstracted from registries of the 14 biggest
      hospitals of St. Petersburg (1989-1990). The analysis showed a statistically
      significant increase in myocardial infarction rate during big geomagnetic
      disturbances, defined by the days of the descending phase of cosmic ray Forbush
      decreases. An overall estimation of the average increase in infarction incidence
      rate during big geomagnetic storms, (10.5 +/- 1.2)%, has been computed by taking
      into account previous results [1-3]. In contrast, morbidity data did not show any
      significant correlation with geomagnetic disturbances. It was found also that the
      infarction incidence rate appears to be rather constant from Monday to Friday and
      to decrease sharply by a factor approximately 1.25 on Saturday-Sunday and mid
      week festivities. This effect is associated with different exposure during work
      days and week-ends to man-made magnetic field environment mainly produced by
      electrified transport. Such effect was not observed in mortality data. The
      results and their methodological aspects are placed in the context of studies on
      possible health effects of low frequency magnetic fields both natural and man
      made origin.

PMID- 9783070
TI  - [Magnetic storms as a stress factor].
AB  - The functional characteristics variations during the magnetic storms were
      observed in both the healthy humans and in patients with cardio-vascular diseases
      as well as in cosmonauts at SOYUZ spacecraft and MIR station. These
      characteristics revealed a nonspecific adaptive stress reaction, which should be
      accompanied by the variations in the stress-hormone production rate. The
      neurohumoral regulation of the organism functions during the geomagnetic storms
      in a group of patients with cardio-vascular pathology and in a control group of
      healthy individuals were studied. The magnetic storm effect characterised of both
      the sick and healthy examines was the violated ratio of glucocorticoids and
      mineralocorticoids, namely increase of cortisone secretion (adrenal cortex
      hormone), as well as some tendency to the activation of sympathoadrenal system.
      Our investigations revealed also a suppressed production of melatonin (the pineal
      gland hormone) during the geomagnetic storm. These results are not in
      contradictions with the functional characteristics violation by the magnetic
      storms and correspond to the existence of adaptive stress reaction of the human
      organism to the geomagnetic field disturbances.

PMID- 9783071
TI  - [Effect of natural factors on the occurrence of cardiovascular diseases].
AB  - The effect of natural environmental factors (indexes of solar activity,
      geomagnetic disturbances, as well as meteorologic parameters: air temperature and
      humidity, and atmospheric pressure) on the occurrence of cardiovascular diseases
      in Ukraine as a whole and in Kiev was analyzed. It is shown that, contrary to the
      stereotype, the yearly dynamics of cardiovascular diseases in 1980-1990 is in
      opposite phase with the solar activity cycle. Similar results were obtained for
      the monthly dynamics of cardiovascular diseases in the period from June 1991 to
      June 1993. The relative influence of five environmental factors (in complex) on
      the daily dynamics of cardiovascular diseases for the same period was calculated.
      The role of heliogeophysical factors becomes especially evident if the daily
      level of cardiovascular diseases within some month of the year is considered.
      This result may be interesting for medicinal practice and forecasting of
      cardiovascular diseases.

PMID- 9783073
TI  - [Assessment of the effect of a geomagnetic storm on the frequency of appearance
      of acute cardiovascular pathology].
AB  - The massif of data about acute coronary pathology and deaths of Central Railway
      Hospital (Moscow) is analysed during 1992-1993. The geomagnetic storms are
      characterised by their intensity and duration. The quantitative values of
      biotropic of the geomagnetic storms are given to different diseases. It is shown
      that during geomagnetic storms the number of cases of myocardial infraction
      increase to 2.5 times, the acute cerebral insult to 2 times, the angina pectoris
      and cardiac arrhythmia to 1.5 times and deaths to 1.2 times in regarding to the
      periods without the geomagnetic storms.

PMID- 9783072
TI  - [Effect of variations of the geomagnetic field and solar activity on human
      physiological indicators].
AB  - The influence of changes in solar and geomagnetic activity on physiological
      parameters of man (EEG, pulse beat, rate of sensomotor reaction and the pressure
      in the period of spring equinox (10.02-10.04.96)) was investigated. The
      correlations between these parameters and variations in the Kp-index were
      obtained. It was found that the oscillations of the Kp-index and alpha-rhythm
      have identical periods.

PMID- 9783075
TI  - [The origin of the biological week from data on the rhythm of cardiac
      contractions in people during the solar activity cycle].
AB  - A human biologic week in the heart rate variations was compared with the
      variations of the sunspot area and geomagnetic activity over the solar cycle. The
      low ratio of amplitude of circaseptan rhythm to that of circadian rhythm in the
      heart rate of several clinically healthy men who did around-the-clock self
      measurements in a number of years coincides with the period of anomalously low
      amplitude of circaseptan rhythm of the solar activity. Results herein suggest
      that physiologic circaseptan rhythms are built into the genome being adapted
      evolutionary to the original heliogeomagnetic environmental circaseptans.

PMID- 9783074
TI  - [Evaluation of the signal-to-noise ratio--"Kullback information"--in the spectrum
      of cardiointervals in arterial hypertension patients depending on cosmophysical
      factors].
AB  - It was shown that Kullback information (In) that is registered in a cardiogram,
      for example, during the arterial hypertension crisis can be used in medicinal
      diagnostics. Periods of In fluctuations from 2 to 12 days were revealed; some
      factors that influence In are shown to have a cosmophysical nature.

PMID- 9783076
TI  - [Heliomagnetic activity and level of extreme situations at the Polar cap].
AB  - It was found that the frequency of extreme situations (traumas, deaths, sudden
      diseases) in miners working in Spitsbergen mines (74 degree N) correlates well
      with heliogeomagnetic activity (local magnetic disturbances, solar proton
      flashes). It was shown that in winter, both an enhanced and an extremely low
      level of magnetic activity can affect the occurrence of extreme situations. The
      results obtained can be used for predicting and reducing the frequency of extreme
      events in the zone of the polar cap during geomagnetic disturbances.

PMID- 9783077
TI  - [Quasi-eleven year modulation of global and spectral features of geomagnetic
      disturbances].
AB  - Variations in spectral characteristics of the Kp-index of geomagnetic activity
      during the solar activity cycle were studied in order to assess the role of its
      rhythms in the formation of temporal structure of biological objects. It is shown
      that most spectral components of the Kp-index are modulated by the 10.5-year
      periodic rhythms in solar activity variations, while its circasemiseptan
      component (3.5 days) exhibits an 11-year rhythm. Since it is a circasemiseptan
      rhythm that is characteristics of biological objects (e.g., unicellular algae),
      it can be assumed that geophysical rhythms played a substantial role in the
      formation of biological rhythms during evolution.

PMID- 9783078
TI  - [Cosmophysical correlation of creative activity in the history of culture].
AB  - The regularities in the creation of outstanding works of painting and poetry, as
      well as scientific discoveries over a period 1400-1800 was estimated
      quantitatively. The occurrence of an about 10-year periodicity of the creative
      activity in West-European and Chinese painting, poetry and science is shown. As a
      rule, the peaks of creative work in China agree with those in West Europe. Since
      the Chinese civilization was not directly connected with the European one, the
      effect of a synchronizing external factor is proposed. It is assumed that
      variations in solar activity serve as such a factor. The study is based on
      historical data on painting, poetry, and scientific discoveries in the period
      from 1400 to 1800.

PMID- 9783079
TI  - [Heliogeophysical factors and aviation accidents].
AB  - It was shown by two independent methods that there is a certain correlation
      between the number of aviation accidents and heliogeophysical factors. The
      statistical and spectral analyses of time series of heliogeomagnetic factors and
      the number of aviation accidents in 1989-1995 showed that, of 216 accidents, 58%
      are related to sudden geomagnetic storms. A similar relation was revealed for
      aviation catastrophes (64% out of 86 accidents) and emergencies (54% out of 130
      accidents) that coincided in time with heliogeomagnetic storms. General
      periodicities of the series were revealed by the method of spectral analysis,
      namely, cycles of 30, 42, 46, 64, 74, 83, 99, 115, 143, 169, 339 days, which
      confirms the causative relation between the number of aviation accidents and
      heliogeomagnetic factors. It is assumed that some aviation accidents that
      coincided in time with geomagnetic storms, are due to changes in professional
      abilities of pilots that were in the zone of storms.

PMID- 9783080
TI  - Assessment after extremely severe head injury in a case of life or death: further
      support for McMillan.
AB  - This paper is a sequel to that of McMillan (1997) and describes further
      assessment of an extremely severely head injured patient. A combination of direct
      observations, structured interviews with staff, simple cognitive tests and
      questions with yes/no answers were used to assess communication and cognitive
      function in an extremely severely head injured patient with minimal ability to
      respond. Results confirmed the finding of McMillan and showed that the patient
      could understand and respond consistently to simple commands, could answer simple
      autobiographical questions consistently and clearly expressed her wish to live.
      The results of this study and that of McMillan confirm that valid assessment of
      minimally responsive patients is possible and that a number of different
      approaches are appropriate.

PMID- 9783081
TI  - Head injury--a survey of current practices in preventive health care counselling.
AB  - OBJECTIVES: This study examined whether primary care physicians provide education
      and counselling on head injury prevention as part of their routine health care
      discussions with patients. METHODS: A preventive health care practices survey was
      distributed to 678 physicians in the Central Virginia area. Data regarding
      respondents' age, gender, medical specialty, patient population and counselling
      practices were obtained. RESULTS: Fifty-one per cent of those surveyed responded.
      Ninety-five per cent of physicians reported providing health care counselling 'in
      most cases' or 'commonly'. Less than half (46%) of physicians discussed head
      injury prevention with their patients. In contrast, almost all respondents (97%)
      discussed smoking. Physician age, specialty, and patient population did not
      affect head injury counselling practices. CONCLUSIONS: Prevention strategies for
      head injury are discussed much less frequently than other health risks such as
      heart disease and cancer in the primary care setting. Strategies for educating
      primary care physicians on head injury should be considered in order to increase
      their efforts toward prevention.

PMID- 9783082
TI  - The role of head injury in cognitive functioning, emotional adjustment and
      criminal behaviour.
AB  - In two investigations, 50% of non-violent convicted felons, who avoided
      incarceration by participating in a day reporting programme, reported a prior
      history of head injury and current problems in cognitive and emotional
      functioning. Only 5% of a college sample in the first investigation and 15% of a
      community sample in the second investigation reported prior head injury. In a
      third investigation, 83% of felons who had reported a history of head injury also
      reported a date for their head injury that preceded the date of their first
      encounter with law enforcement. Some participants reported no trouble with the
      law until after experiencing a head injury that occurred in their late thirties.
      Considering the research reported here and elsewhere in the literature, it
      appears that many serious crimes follow a head injury. One implication of the
      findings reported here is that many crimes might not occur if people with head
      injury were given prompt and comprehensive treatment after the injury.

PMID- 9783083
TI  - Motor performance following a mild traumatic brain injury in children: an
      exploratory study.
AB  - Mild Traumatic Brain Injury (TBI) is a common occurrence in the paediatric
      population and, as the concept of motor performance has not been assessed
      specifically in this population, the purpose of this study was to determine if
      motor performance deficits are present and can be objectively identified in a
      sample of children having sustained a mild TBI (Glasgow Coma Scale score 13-15).
      Twenty-eight children aged between 5 and 15 years were recruited immediately post
      trauma. Subjects were considered normal on standard neurological exam at the time
      of discharge. They were assessed 13-18 days post-trauma using the Bruininks
      Oseretsky Test of Motor Proficiency, a norm referenced clinical standardized
      assessment tool. Compared to published norms, motor performance was significantly
      lower in domains of balance, response speed and running speed an agility (t-test
      p < 0.01), and significantly higher in domains of upper extremity coordination
      and visual motor control (t-test p < 0.01). Although excellent performance can be
      observed in domains requiring upper limb coordination, motor planning and
      execution of motor tasks, deficits in balance and response speed can be
      identified in a significant number of children even after mild TBI. More specific
      and sensitive evaluations are necessary to identify the exact nature of the
      problems and evaluate their functional impact on daily activities.

PMID- 9783084
TI  - Perceptions of care access: the experience of rural and urban women following
      brain injury.
AB  - To examine care access among women with brain injuries, a qualitative,
      phenomenological study was conducted. Twenty-one women with acquired brain
      injuries were recruited for the inquiry, representing rural and urban regions of
      Colorado. The phenomenological approach allowed the investigators to examine the
      shared experiences of women with brain injuries as they sought rehabilitative
      supports and services, and attempted to re-enter their lives and communities.
      Each woman was interviewed one or two times, the interviews were transcribed and
      then coded and analysed by both authors separately. Thematic analysis of the data
      revealed two major emergent themes: issues surrounding diagnosis and barriers to
      accessing care. A total of 10 women interviewed experienced difficulty obtaining
      a diagnosis of brain injury and experienced serious personal and professional
      consequences as a result. All the women experienced barriers to accessing care,
      including problems with service providers and service systems, financial
      challenges, travelling for services, lack of information or services in their
      area, lack of care coordination and funneling. Some of the barriers cannot be
      changed secondary to cost, efficiency and logistics. Other barriers, could be
      changed through education, training and policy making.

PMID- 9783085
TI  - Everyday planning difficulties following traumatic brain injury: a role for
      autobiographical memory.
AB  - The present study examines the role of autobiographical memory in describing how
      to perform both open-ended and closed everyday activities in 12 patients
      suffering traumatic brain injury and 12 aged-matched controls. The frequency
      (high versus low) of performing the activities was also manipulated. Patients
      seemed less well able to benefit from using specific autobiographical memories;
      they reported using significantly fewer specific autobiographical memories for
      describing how to perform low-frequency activities and significantly more such
      memories for high-frequency activities compared with controls. The quality of
      their descriptions was also significantly poorer for the open-ended activities.
      Finally, significant correlations were found between the quality of the
      descriptions and the retrieval of specific autobiographical memories for the
      controls only. The importance of the retrieval of specific autobiographical
      memories for everyday problem-solving is discussed.

PMID- 9783086
TI  - Recovery and rehabilitation following subarachnoid haemorrhage: Part II. Long
      term follow-up.
AB  - BACKGROUND AND PURPOSE: Subarachnoid haemorrhage (SAH) accounts for 5-10% of all
      strokes, strikes at a mean age of 50 years and results in a pattern of deficits
      similar to that of traumatic brain injury. This study is an extension of a
      previous study which described outcome at discharge from inpatient
      rehabilitation. The purpose of this follow-up study was to describe long-term
      functional, cognitive and psychosocial outcome in a cohort of SAH survivors who
      received inpatient rehabilitation. METHODS: Subjects were interviewed by
      telephone. Functional status was assessed using the Functional Independence
      Measure (FIM) and cognitive status with the Telephone Interview for Cognitive
      Status (TICS). Social function was determined via a brief questionnaire. RESULTS:
      Thirty two out of 80 subjects who received inpatient rehabilitation participated
      in the study. The 32 did not differ from the original group of 80 on any
      demographic or clinical criteria. The mean time from onset of SAH to follow-up
      was 28 months. Total FIM scores improved significantly between discharge and
      follow up (p < 0.0001) and most subjects functioned at a physically independent
      level. However, almost 40% scored in the cognitively impaired range on the TICS.
      Between 40% and 50% required help with common household activities, and none
      returned to full-time work. Functional and cognitive outcome was not related to
      any demographic or clinical characteristics at SAH onset. CONCLUSION: The
      majority of SAH survivors who received inpatient rehabilitation attain physical
      independence, but many continue to have cognitive impairments which result in
      social and vocational disabilities.

PMID- 9783087
TI  - Post-craniectomy intracranial hypotension: potential impact on rehabilitation.
AB  - More aggressive neurosurgical management of intractably elevated intracranial
      pressure has resulted in increased survival of severely brain injured patients,
      many of whom are transferred for inpatient rehabilitation status post
      craniectomy. Positional headache due to intracranial hypotension has been
      described in the literature, but is rarely reported as a complicating factor for
      patients receiving rehabilitation therapies. Low cerebrospinal fluid (CSF)
      pressure symptoms include postural headache, vertigo, nausea, vomiting, visual
      symptoms, auditory symptoms, and rarely cognitive changes. This report describes
      a patient who sustained a severe traumatic brain injury requiring craniectomy for
      management of increased intracranial pressure who subsequently developed
      intracranial hypotension. One month post-craniectomy, she developed postural
      headaches with cognitive and functional decline, which significantly impaired her
      rehabilitation. Aggressive efforts at conservative management including hydration
      and empiric blood patch were unsuccessful. Once the bone flap was replaced, she
      made rapid and dramatic functional gains, with total resolution of headache. This
      paper hypothesizes that the mechanism of low CSF pressure after extensive
      craniectomy is related to loss of hydrostatic pressure following removal of the
      skull vault. In rehabilitation of severely brain injured patients with
      craniectomies, it is important to recognize and appropriately treat this syndrome
      to avoid compromising patient care and prolonging hospitalization.

PMID- 9783088
TI  - TRI-PLEDs.

PMID- 9783089
TI  - Frontal lobe epilepsy: the next frontier.
AB  - Frontal lobe epilepsy, the great new epileptological challenge, presents enormous
      difficulties that still preclude a more profound understanding at the present
      time. The major subdivision of the frontal lobe into a prefrontal and premotor
      portion is the first step toward a better and yet limited comprehension of the
      frontal lobe epilepsies. Prefrontal implies higher mental functions (e.g., ictal
      forced thinking); rapid generalization to full grand mal evolves quite often from
      prefrontal foci. The frontal accentuation of classical generalized 3/sec spike
      wave absences adds to the conceptual difficulties of the frontal lobe epilepsies.
      The unique type of disturbed consciousness in classical absences is presumed to
      be based upon ictal "suspension of the working memory." Limbic components (via
      orbitofrontal and cingulate mechanisms) also play an important role. Correlations
      between ictal semiologies and regional frontal lobe functions are still quite
      controversial.

PMID- 9783090
TI  - Interhemispheric EEG coherence in never-medicated patients with paranoid
      schizophrenia: analysis at rest and during photic stimulation.
AB  - We assessed functional relationships between hemispheres by calculating
      interhemispheric EEG coherence at rest and during photic stimulation in 18 never
      medicated patients with paranoid schizophrenia and 30 control subjects. Although
      no significant group differences were found in the resting EEG, the schizophrenic
      patients had significantly higher coherence on EEGs recorded during photic
      stimulation, compared to the control subjects. In this study, we also examined
      the changes in interhemispheric coherence from rest to the stimulus condition
      (i.e., stimulation-related coherence reactivity); the patients were found to show
      significantly greater coherence reactivity to photic stimulation. These findings
      provide further evidence that schizophrenic patients have a higher degree of
      interhemispheric functional connectivity and thus have less lateralized cerebral
      organization than normal subjects. Our results also suggest that schizophrenic
      patients have excessive functional reorganization between hemispheres in
      association with photic stimulation.

PMID- 9783091
TI  - Concomitance of childhood absence and Rolandic epilepsy.
AB  - Five children (3 girls and 2 boys) who showed generalized synchronous 3/sec spike
      and wave complexes as well as centrotemporal spikes in the same EEG or in
      different EEGs are described. Among these five patients only 1 boy and 1 girl
      showed clinically both absence seizures and partial motor seizures with or
      without secondary generalization. One girl and 1 boy have only absences and the
      other girl only partial motor seizures. A concomitance of generalized synchronous
      3/sec spike and wave discharges and centrotemporal spikes in the same patient is
      rarely found. The clinical manifestation of absences and partial motor seizures
      in the same patient is extremely rare.

PMID- 9783093
TI  - The development of the vertex sharp transient.
AB  - The development of the vertex sharp transient (VST) was studied in 35 infants of
      ages from 10 wk until 40 mo. At 10 wk bicentral rhythms of 3-4/sec can be seen,
      at first asymmetrical, later symmetrical and "pieces" of this rhythm can
      occasionally appear. At 6 mo a few broad VST appear, but the earliest discrete
      VST appears around 16 mo, becoming sharper with a shorter duration at 24 mo and
      repetitive at 30 mo. Measurements reveal considerable variability in both
      amplitude and duration before 18 mo, after which the duration is typically around
      100 msec, but with increasing variability in the amplitude difference between the
      two sides. These changes in the VST are discussed in relation to a recent study
      on the K-complex showing 3 well-defined frequency bands at < 1 Hz, 1-4 Hz and 12
      15 Hz. Thus, the major developmental changes of the vertex sharp transient are
      that they become sharper, shorter in duration and more repetitive in time, and at
      around 16 mo are similar to the typical discrete pattern seen in older children
      and adults.

PMID- 9783092
TI  - The effect of hyperventilation on the frequency of Rolandic spikes.
AB  - We have shown in this study of 20 patients that the frequency of Rolandic spikes
      was significantly lower during hyperventilation and the 2 minutes following
      hyperventilation than during normal wakefulness.

PMID- 9783094
TI  - Electrophysiological changes in children with learning and attentional
      abnormalities as a function of age: event-related potentials to an "oddball"
      paradigm.
AB  - This study investigated age-related electrophysiological differences between
      children diagnosed with Learning Disabilities (LD), Attention Deficit
      Hyperactivity Disorder (ADHD), LD-ADHD and Conduct Disorder, using Event-Related
      Potentials recorded during a two-tone discrimination test. Although age-related
      (N1 and N2 amplitude), as well as diagnostic group-related (P3 latency and
      amplitude) ERP changes were found, there was no significant interaction between
      the diagnostic groups and age grouping. We conclude that: 1) Electrophysiological
      abnormalities in LD and ADHD do not significantly change with age during
      childhood. This study does not, therefore, support a hypothesis of age-related
      brain abnormalities in LD and ADHD. 2) Significant group differences for P3
      latency and amplitude were found between normal children and the LD groups (LD
      and LD-ADHD), but not between normal children and those with ADHD alone,
      suggesting that main correlates of P3 abnormalities in these children are
      "processing" and not attentional problems.

PMID- 9783095
TI  - Improvement of P300 latency by treatment in non-insulin-dependent diabetes
      mellitus.
AB  - P300 event-related potentials were investigated in 24 cases of non-insulin
      dependent (Type II) diabetes mellitus (NIDDM) without apparent central nervous
      system (CNS) symptoms and without cerebrovascular diseases on head magnetic
      resonance imaging, and in 16 age-matched healthy control subjects. N200 and P300
      latencies were significantly prolonged and N200 and P300 amplitudes were
      significantly smaller in the NIDDM group than in the healthy control group. P300
      latency was significantly shorter after the treatment than before. N200 and P300
      waves have been recognized as useful indicators of cognitive function. The
      present study suggests that cognitive function is impaired in NIDDM patients and
      may improve with treatment of hyperglycemia.

PMID- 9783096
TI  - EEG seizure in bilateral ECT is different between low and high stimulus doses.
AB  - Melancholic depressive patients referred for ECT were randomized to receive
      either low dose (n = 20) or high dose (n = 20) stimulus applied
      bifrontotemporally. The two stimulus groups were comparable on the clinical
      variables. The EEG seizure was recorded on two channels (right and left frontal),
      digitized, coded and analyzed offline without knowledge of ECT parameters. EEG
      seizure was of comparable duration in the two stimulus (high dose and low dose)
      groups. A new composite measure, Strength-Symmetry-Index (SSI), based on strength
      and symmetry of seizure EEG was computed using fractal geometry. The SSI of the
      early-seizure was higher in the high dose than in the low dose ECT group. In a
      stepwise, logistic regression model, this variable contributed to 65% with
      correct classification of high dose and low dose ECT seizures.

PMID- 9783097
TI  - [Nootropic preparations, the achievements and new problems].
AB  - Recent studies in the field of molecular neurochemistry have demonstrated new
      mechanisms of regulation of the processes of training and memory, and on the
      basis of this new nootropic agents have been created. This work analyses in
      detail the most promising directions of research into the development of new
      nootropics acting on the deficiencies of synaptic transmission (cholinergic,
      glutamatergic. GAMA-ergic), free-radical affections, and peptidergic processes.
      Chemical heterogeneity, the wide variety of effects, and the difference in the
      mechanisms of action of the family of nootropics creates essential difficulties
      in the definition, classification, and determination of the mechanism of the
      nootropic effect proper, which is a frequent cause of the disagreement between
      the experimental and clinical data. Discussion of these problems is the subject
      of the present article.

PMID- 9783098
TI  - [The effect of rudotel on the synaptic activity of dopaminergic neurons].
AB  - The work discusses the neurochemical correlates of rat brain dopamin-synaptic
      activity after injection of 0.5 mg/kg rudotel (medazepam) as compared with intact
      animals. The parameters of functioning of D2-receptors in [3H]-dopamine binding,
      the content of catecholamines and their metabolites (high-performance liquid
      chromatography with electrochemical detection) were studied in the dopaminergic
      system in different brain areas (the striatum, frontal cortex, amygdala,
      hippocampus, hypothalamus, and accumbence).

PMID- 9783099
TI  - [The effect of gidazepam on the level of monoamines in the brain of BALB/c mice].
AB  - The authors studied the content of norepinephrine, dopamine, serotonin, and their
      metabolites in the hypothalamus and striatum of BALB/c mice after injection of
      tranquilizers phenazepam (0.05 mg/kg) and hydazepam (1 mg/kg). The drugs differed
      in their effect on the monoamine content in the brain structures under study,
      which was evidence of the difference in the mechanisms of their action.

PMID- 9783100
TI  - [The neurotropic activity of peptide immunomodulators].
AB  - Four-day monitoring using standard methods of studying free group behavior of
      animals in an "open field" (Opto-Varimex, USA) showed that all the peptide
      immunomodulators under study possessed a neuromodulating effect comparable with
      that of known drugs. They change the character of the circadian rhythms of the
      animals' motor activity and the dynamics of extinction of the orientation
      investigation reaction. In comparison with the control the activity of the drugs
      under study was distributed as follows: ethymizol > cerebrolysin > thymalin >
      nootropil > thymogen > T-activin > cortexin > dibazol.

PMID- 9783101
TI  - [The characteristics of the analgesic action of nitrosorbide and no-shpa].
AB  - The study was conducted on experimental models of pain sense induced in mice by
      exposure to thermic or chemical factors and in rats by exposure to electric
      factors. Nitrosorbide and no-spa possess a dose-dependent analgesic effect. Both
      drugs excelled analgin in the intensity and duration of analgesic effect.

PMID- 9783102
TI  - [A comparison of the clinical efficacy of enalapril maleate analogs in patients
      with heart failure and ischemic heart disease].
AB  - The authors examined 68 patients aged from 42 to 68 years with ischemic heart
      disease without a history of myocardial infarction and with angina pectoris of
      exertion functional class 2-3 and circulatory insufficiency class 2 (according to
      NYHA criteria). The criteria serving as the reason for relating patients to the
      follow-up group were left-ventricular end-diastolic volume > 160 ml, ejection
      fraction < 30%, cardiothoracic index > 0.55, threshold power of endured loads
      within a range of 71.5 +/- 2.30 watt. After stabilization of the clinical status
      by means of basic therapy (nitrates, blockers of slow calcium channels,
      diuretics, antiaggregants), all patients were divided into two follow-up groups.
      The first group consisted of 36 patients who received renitec (10 mg/24 h),
      patients of group 2 were given enap in the same dose. The course of treatment
      lasted 12 weeks. The effectiveness of treatment was controlled by
      echocardiography according to the standard methods in M- and B-regimens. Analysis
      of the obtained data showed that within 12-day follow-up renitec demonstrated
      higher effectiveness and lesser incidence of side-effects than did enap given in
      the same dose.

PMID- 9783103
TI  - [The effect of pyrimidine derivatives on experimental stomach ulcers in rats].
AB  - Experiments on albino rats showed that pyrimidine derivatives reduce hemorrhagic
      damage of the gastric mucosa caused by indomethacin, acetylsalicylic acid, and
      ortophen. The derivatives of pyrimidine prevent the decrease in total acid
      phosphatase activity, increase alkaline phosphatase, and reduce the activity of
      lactate dehydrogenase.

PMID- 9783104
TI  - [A comparative evaluation of the action of kvamatel and omez on the glutathione
      system in different sections of the digestive system in experimental duodenal
      ulcer].
AB  - Experiments on male albino rats demonstrated significant changes in the content
      of oxidized and reduced glutathione in the tissues of the liver, pancreas,
      stomach, duodenum, and small intestine in acetate ulcer of the duodenum.
      Experimental therapy with quamatel and particularly with omez led to activation
      of the glutathione system in the tissues under and in this way increased their
      resistance to the ulcerogenic effect.

PMID- 9783105
TI  - [The pharmacodynamics and pharmacokinetics of furosemide during ordinary life
      activities and during head-down tilt hypokinesia in a healthy subject].
AB  - The object of the work was comparative study of the characteristics of
      pharmacodynamics and pharmacokinetics of the diuretic furosemide during ordinary
      vital activity of man and under conditions of antiorthostatic hypokinesia. Six
      practically healthy males were examined. They took part successively in two
      experimental series: series 1--during an ordinary motor regimen under ambulatory
      conditions; series 2--under conditions of antiorthostatic hypotension (ANOH, 12
      degrees). In both series with absolute correspondence of the procedures and order
      of manipulations the subjects were given 40 mg furosemide per os, venous blood
      and urine were repeatedly tested, and the physiological data were recorded. In
      combined action of an antiorthostatic position of the body and the diuretic an
      additive effect was encountered, i.e., increased therapeutic effect of,
      furosemide. The blood serum electrolyte composition practically did not change in
      this case. After oral administration of 40 mg furosemide maximal concentration of
      the drug in the blood (977 +/- 151 ng/ml) was found on the average in a group in
      1.3 +/- 0.2 h. The drug half-life period in this case was 1.1 +/- 0.4 h; total
      clearance was 24.7 +/- 2.8 liter/h, and the distribution volume was 33.7 +/- 12.7
      liters. In maintenance of antiorthostasis furosemide pharmacodynamics and
      pharmacokinetics changed but the individual character of the dynamics of drug
      concentration in the blood persisted. No statistically significant differences in
      the mean group pharmacokinetic parameters of the drug during an ordinary motor
      regimen and in antiorthostatic hypokinesia were encountered. Furosemide given in
      antiorthostatic hypokinesia led to diminished filling of the upper and middle
      parts of the lungs with blood despite the attendant decrease in the tonus of the
      resistant vessels.

PMID- 9783106
TI  - [Disorder of the serotoninergic regulation of bone marrow cell proliferation
      under the action of a xenobiotic inducer of oxidative stress].
AB  - The work shows the results of experimental study of the characteristics of
      serotonin regulation of cell proliferation and programmed cell death in bone
      marrow cells cultivated in diffusion chambers. It was found that the change in
      cell colony and cluster formation and death induced by this biogenic enzyme is
      disturbed by acrylamide, an inducer of oxidizing stress. Nicotinamide levels out
      the effect of acrylamide, which is evidence of the existence of NAD-dependent
      mechanisms in the serotonin-mediated regulation of hemopoiesis.

PMID- 9783107
TI  - [The energy parameters of the liver mitochondria under the prolonged action of
      halothane in vitro].
AB  - The effect of 10-, 30-, 60-, 90-, and 120-min exposure to halotane vapors on the
      energy parameters of mitochondria of the liver of albino rats was studied in in
      vitro experiments. In long-term contact of the mitochondria with halotane the
      respiratory and phosphorylation function of the mitochondria in oxidation of PAD-
      and NAD-dependent substrates was disturbed.

PMID- 9783108
TI  - [The immunotropic activity of erakond].
AB  - The effect of eracond on some parameters of immunity and allergic reactions was
      studied in experiments on mice and guinea pigs. The drug was found to possess an
      immunomodulating effect.

PMID- 9783109
TI  - [A comparative study of the activity of a natural peptide complex in the kidneys
      and its synthetic analogs in autoimmune nephritis].
AB  - The activity of the natural peptide complex of the kidneys and of its synthetic
      analogs (PEKDLRK, PEKDSRK, PEKDDRL) in autoimmune nephritis was studied on golden
      hamsters. All the peptides under study demonstrated therapeutic activity but were
      characterized by peculiarity of their effect. The peptide PEKDLRK possessed the
      most marked capacity for stimulating phagocytic reactions, PEKDDRL apparently
      activated the system of natural killers. It is concluded that the study of
      peptides-analogs as potential drugs is promising.

PMID- 9783111
TI  - [The effect of thymosin fractions on the development of compression edema
      swelling of the brain].
AB  - The search for pathogenetically drugs for the treatment and prevention of edema
      swelling of the brain (ESB) is one of the urgent problems of modern biology and
      medicine. Immune reactions take part in the development of pathological reactions
      in ESB formation. The antiedemic action of drugs affecting simultaneously the
      processes in the nervous and immune systems was studied. Such properties are
      possessed by regular peptides--thymosin fractions. It was demonstrated on a model
      that the antiedemic effect of thymic peptides under study was due to the
      influence of the mediator systems: serotonin and adrenergic. The data obtained
      allowed the antiedemic mechanism of the effect of thymoptin to be associated with
      its immunostimulating effect. At the same time, the antiedemic effect of thymalin
      is not connected directly with the immunostimulating action of the drug.

PMID- 9783110
TI  - [The bioavailability of tableted drug forms of the new Russian nootropic
      preparation nooglutil in rabbits].
AB  - Comparative study of the main pharmacokinetic characteristics and evaluation of
      the bioavailability of two experimental tablet forms of the new nootropic
      nooglutil in relation to the substance of the drug were conducted on rabbits. The
      nooglutil content in plasma samples was determined by high performance liquid
      chromatography. Significant advantage of one tablet of the drug containing tween
      80 was demonstrated. Bioavailability of this drug form of nooglutil in relation
      to the substance of the drug was 104.3%.

PMID- 9783112
TI  - [The effect of dimethyl sulfoxide on the changes in the lymph microcirculation
      induced by staphylococcal toxin].
AB  - The effect of dimethyl sulfoxide (dimexid, DMSO) on the lymph microvessels of the
      rat mesentery was studied by vital biomicroscopy. It was found that 30% DMSO
      increases the tonus of intact lymph microvessels and stimulates their phase
      contractions. Action of the agent for more than 15 min leads to the development
      of lymphostasis. DMSO has a pronounced corrective effect on disorders of lymph
      microcirculation caused by the staphylococcal toxin. It removes the main
      lymphopathogenic effects of the poison and normalizes the drainage function of
      the lymphangions. The correcting effect of DMSO on lymph circulation is attended
      with attenuation of the fatal effect of the toxin.

PMID- 9783113
TI  - [Apoptosis: the pharmacological aspects].
AB  - The article deals with the latest achievements in the interpretation of the
      mechanism of programmed cell death (apoptosis). The effect of drugs on the
      different stages of the apoptotic signal conduction is analysed. The earliest
      prospects of creating apoptosis regulating agents are planned. It is suggested
      that tests for apoptosis should be included in the list of obligatory ones in the
      preclinical studies of new biologically active compounds.

PMID- 9783114
TI  - [The pharmacological regulation of thrombocyte activity].
AB  - Among the main means of producing a pharmacological effect on the functional
      activity of blood platelets are blockade of the specific membrane receptors,
      inhibition of the activity of the enzymes cyclooxygenase and thromboxane
      synthetase, increase in the cell cAMP and cGMP content. The intracellular level
      of free calcium constants is the main link in platelet activity regulation. A
      classification of antithrombocytic compounds based on the main site of their
      action is suggested. The effectiveness of drugs affecting the initial and final
      stages of the cascade mechanism of platelet activation is substantiated.

PMID- 9783115
TI  - [Antihypoxants: their status and outlook].
AB  - The survey deals with the up-to-date information in the literature on the problem
      of pharmacological correction of pathological changes found in the organism in
      the hypoxic syndrome. The principal approaches to pharmacotherapy of this
      pathological condition are pointed out. Information on the up-to-date and
      effective antihypoxia agents applied in medical practice and those in the stage
      of development is given.

PMID- 9783116
TI  - [Pain-relieving agents: a comparative evaluation, mechanisms of action and
      outlook].

PMID- 9783117
TI  - The aging effects on the EMG and mechanical responses of the human wrist flexor
      stretch reflexes.
AB  - The purpose of this study is to investigate the effects of aging on the human
      stretch reflexes. The EMG and torque responses of the stretch reflex of the wrist
      flexors were evoked by ramp-and-hold mechanical perturbations. The stretch
      reflexes were recorded at seven test conditions with different stretch velocity
      and muscle preload. The test results from young and older healthy adult subjects
      were compared. In average, the absolute amplitude of the short-latency (20-40 ms)
      EMG (recorded from flexor carpi radialis) reflex response was significantly lower
      in the older group. If the data were normalized and expressed in percentage of
      the maximal voluntary EMG activity, however, this group difference was not
      significant. There was no change in the reflex gain of the short-latency reflex
      with aging. For the long-latency (50-90 ms) EMG reflex response, both the
      normalized amplitude and the reflex gain were significantly enhanced with aging,
      probably through supraspinal mechanisms. There was no significant difference in
      the threshold velocity for the evoked EMG reflexive activities between age
      groups. There were also no changes in the reflexive wrist flexion torque with
      aging. These results suggested that the number of motor units recruited during
      the stretch reflex activity declined with aging although the percentage of motor
      units recruited was not affected by aging. It is concluded that the central
      regulating mechanisms of the spinal motoneuron excitability are not compromised
      by aging. The automatic gain compensation phenomenon is also preserved with
      aging.

PMID- 9783118
TI  - Study of central and peripheral conductions to the diaphragm in 22 patients with
      definite multiple sclerosis.
AB  - Involvement of the diaphragm was evaluated electrophysiologically in 22 patients
      with definite multiple sclerosis. Magnetic transcranial stimulation (MTS),
      magnetic cervical stimulation at C4 level (MCS) and electric stimulation of the
      phrenic nerve at the neck (EPS) were performed for measuring latencies, motor
      conduction times and amplitudes of the responses recorded with a pair of surface
      or subcutaneous electrodes located at the xiphoid and the 8th costal interspace
      on the anterior axillary line. Latency of the motor evoked potentials (MEPs) was
      abnormal: in 9 patients following MTS, in 6 following MCS, in 2 following EPS.
      The motor conduction time between the cortex and the cervical spine, we called
      CMCT1, was abnormal in 11 patients and the motor conduction time between the
      cortex and the neck, we called CMCT2, was abnormal in 8 patients. However CMCT1
      was more often unmeasurable than CMCT2 because the MEPs following MCS were
      unreliable in 4 patients. The conduction time between the cervical spine and the
      neck was abnormally long in 2 patients but it was paradoxically abnormally short
      in 3, probably because of the difficulties in locating exactly the place of the
      stimulation at the cervical C4 level. The MEP amplitude was not considered a
      reliable parameter because of the large range of the values in our controls,
      although the mean amplitude was significantly lower in the patients than in the
      controls. The amplitude of the compound muscle action potential (CMAP) following
      EPS was below the lower limit of the normal in 9 patients. The percentage of
      abnormal MEP latencies and CMCTs when both sides were combined was higher for the
      hemidiaphragms than for the upper limbs and was roughly the same for the
      hemidiaphragms and the lower limbs. Moreover electrophysiological study of the
      diaphragm was abnormal in 5 patients without pulmonary symptoms and with normal
      pulmonary function tests, demonstrating that this study is useful for revealing
      infraclinical demyelinating lesions on the central motor pathways down to
      diaphragm. In addition, alterations of the CMAPs in some patients suggest a
      possible extension of the lesions towards the anterior horns and anterior roots.

PMID- 9783119
TI  - Correlation between denervation activity and compound muscle action potential
      amplitude in hereditary motor and sensory neuropathy I and II.
AB  - Studying the electrophysiological characteristics of the various types of Charcot
      Marie-Tooth disease is important in the understanding of its pathophysiology. The
      purpose of this study was to identify the frequency of fibrillation potentials
      and positive sharp waves (FP/PWs) in HMSN I and II and, since they are indices of
      denervation, to elucidate whether they are correlated with the amplitude of
      compound muscle action potentials (CMAP). We reviewed the electrophysiological
      findings of 47 patients who have been studied in our hospital and found to suffer
      from Charcot-Marie-Tooth polyneuropathy. FP/PW were graded according to a 4-grade
      scale and the 38 m/sec criterion for motor conduction velocity (MCV) was used for
      distinction between HMSN I and II subgroups. Seventy percent of HMSN II patients
      and 81% of HMSN I patients showed fibrillation potentials in the upper or lower
      limbs. There was no difference in the frequency of FP/PW appearance between the
      two groups. In the HMSN II group the FP/PW grade correlated with CMAP amplitude
      in the upper limbs. In both groups there was no correlation between FP/PW grade
      and MCV. Our findings might indicate that in HMSN I there is a considerable
      axonal destruction that occurs concurrently with myelin loss.

PMID- 9783120
TI  - Effect of agonist load on fastest muscle contractions in human elbow flexors.
AB  - The purpose of this study was to investigate whether the central nervous system
      (CNS) motor program subserving most-rapid voluntary force pulse generation is
      modified according to the level of agonist muscle load maintained prior to the
      pulse. Five normal subjects produced most-rapid force pulses to a target of 20%
      maximum voluntary force (MVF) above different levels of steady tonic contraction.
      Time to reach peak force, the first agonist burst duration and area were
      relatively constant for loads up to approximately 40% of MVF and then increased
      substantially with larger loads. These results indicate that the CNS adjusts
      agonist burst amplitude and duration in order to accomplish the same rapid motor
      task depending on the load. It is argued that these adjustments are necessary to
      compensate for physiological limitations of motor unit behavior and non-linearity
      between EMG activity and phasic force output.

PMID- 9783121
TI  - Peripheral nerve conduction in healthy subjects during short-term hyperglycemia.
AB  - Aim of the present study was to evaluate the effect of acute hyperglycemia on
      peripheral nerve conduction measurements. Five healthy male volunteers aged 36-42
      years underwent nerve conduction studies during hyperglycemia (blood glucose
      approximately 12 mmol/l) induced by intravenous infusion of glucose and
      maintained for 120 minutes. Peroneal motor and sural sensory nerve conduction
      velocities and amplitudes were measured from the right leg at 15 min intervals
      starting at 15 min before and continuing 30 min after glucose infusion. Data were
      analysed using paired t-test comparing measurements at each time point after the
      start of the infusion to the second control measurement immediately prior to the
      infusion. All nerve conduction velocities and amplitudes were similar before,
      during and after induced hyperglycemia. The results suggest that it is
      unnecessary to standardise blood glucose concentration during measurement of
      peripheral nerve functions.

PMID- 9783122
TI  - Developmental changes of impulse transmission in rat gastrocnemius muscles
      revealed by neostigmine.
AB  - Developing rats between 5 and 44 days of age as well as rats about 2 months old
      were anesthetized with urethane. Spontaneous activities and muscle potentials to
      sciatic stimuli were recorded from their exposed medial gastrocnemius muscles
      using concentric electrodes. Neostigmine of 0.12-0.40 mg/kg was injected into the
      contralateral muscles. Regardless of age, spontaneous activities were not
      observed and muscle potentials were evoked by single stimuli primarily in a
      biphasic wave (main component) before the drug treatment. Developmental
      differences were revealed in the presence of the drug. 1) Spontaneous activities
      were detected only in single spikes around postnatal 10 days. Single or double
      spikes were often found in rats of about two weeks. Burst discharges such as seen
      in adult rats were observed immediately before weaning. 2) In rats of 2 weeks or
      so, one or more components were observed obscurely following the main component
      of muscle potentials, which appeared definitely at the preweaning period. 3) When
      double shocks with the interval of 2 sec were delivered in the presence of the
      drug, the second potential was greatly depressed in rats older than two weeks as
      well as in adult rats. The potential was only slightly reduced in rats around 10
      days. Thus, an adult pattern as to impulse transmission was observed immediately
      before weaning. These alterations would, at least in part, reflect the maturation
      of acetylcholine receptors at neuromuscular junctions.

PMID- 9783123
TI  - Sacral reflex latency correlated by age and sex.
AB  - This prospective study was undertaken on 190 subjects who had no prior central or
      peripheral nerve supply pathology and where the value of the sacral reflex
      latency was compared by age and sex in order to determine precise norms. There
      were 90 men whose age averaged 56.9 +/- 13 years and 100 women with an average
      age of 54 +/- 13.1. The reflex was obtained by stimulating the dorsal nerve of
      the penis and the clitoris and taking a reading in the intermediate part of the
      external anal sphincter muscle. An averaging technique was used (over 30
      stimulation occurrences). The average intensity of the stimulation was 15 mA. The
      value of the stimulus reaction latency taken at the positive peak was analyzed
      statistically. The average value was 37.6 +/- 5.36 ms in male subjects and 46.6
      +/- 8.08 in female subjects. In men, values varied from 36.6 +/- 4.26 ms at under
      35 years of age and reached 42 +/- 3.52 ms at over 75 years. In women, values
      varied from 37.33 +/- 7.69 ms at under 35 years to 55.6 +/- 4.39 ms at over 75
      years of age. In a previous article we discussed ageing features in nerves and
      muscles. These features are largely responsible for the occurrence of static
      pelvic problems. The purpose of this study is to compare the sacral reflex
      latency by sex and age in normal subjects.

PMID- 9783124
TI  - EMG findings in acute myopathy with status asthmaticus, steroids and paralytics.
      Clinical and electrophysiologic correlation.
AB  - We have reviewed the clinical and electrophysiologic features of eleven
      mechanically ventilated patients with asthma who developed persistent weakness
      following treatment with neuromuscular blocking agents and corticosteroids. All
      patients had electrophysiologic findings consistent with a myopathic process and
      no evidence of a neuromuscular transmission disorder or generalized neuropathy.
      Electrophysiologic improvement paralleled clinical improvement. The severity of
      the initial electrophysiologic findings did not predict the subsequent rate of
      recovery. All patients showed substantial recovery (to functional independence)
      over the first month.

PMID- 9783125
TI  - Afterdischarges following F waves observed in a patient with tetanus.
AB  - We report a case of non-fluminent and mildly affected tetanus patient who showed
      afterdischarges following F waves in the affected extremity. The afterdischarges
      occurred following F waves and showed different configuration respond to each
      stimuli. Diazepam was also effective for spasms of our patient. This finding
      disappeared after treatment and showed a good correlation to clinical symptoms.
      These observations suggest that afterdischarges following F waves are induced by
      tetanus toxin which puts most of the motor neuron pool in a hyperactive state
      through its own action to the motor nerve including the spinal motor neuron.

PMID- 9783126
TI  - H reflex excitability following voluntary muscle contraction of different
      duration.
AB  - The importance of the duration of contraction on the excitability of the
      motoneuronal pool was evaluated by measuring the H reflex from soleus muscle
      after short and long contractions at constant effort equal to 60% maximal
      voluntary contraction (MVC); the difference between the amplitude of H reflex at
      rest and after contraction of different duration was evaluated in 10 normal
      subjects and in one hemiparetic patient. The authors found a significant
      inhibition of H reflex after contraction of 10 seconds and after 40 seconds and a
      longer duration of the inhibition after 40 seconds. In the hemiparetic patient
      the H reflex did not show inhibition which suggests a possible reduction of the
      presynaptic inhibition, and a lack of modulation of the motoneuronal pool after
      contraction.

PMID- 9783128
TI  - Improvement in inner ear blood flow by nitric oxide following experimentally
      induced cochlear thrombosis in anesthetized guinea pigs.
AB  - The nitric oxide (NO) donor sodium nitropruside (SNP) applied to the round window
      membrane has recently been found to increase cochlear blood flow (CoBF) in normal
      guinea pigs and in normal and presbyacusic mice. This study examined the effect
      of topical applications of SNP on experimentally impaired CoBF in anesthetized
      guinea pigs. Small (3 microliters) portions of 3% SNP were applied to the round
      window niche of both normal and thrombosed cochleas. Local vascular impairment
      was produced by ferromagnetic thrombosis of cochlear blood vessels and the
      microcirculation measured using laser Doppler flowmetry. Ferromagnetic thrombosis
      resulted in a mean decrease of CoBF to 52% of baseline. There was a clear
      improvement in mean CoBF to 84% of baseline by the topical application of SNP
      that depended on the degree of ischemic damage produced. Under neuroleptanalgesia
      and ketamine-xylazine anesthesia, significant increases in CoBF were measured in
      normal ears as well as in the thrombosed ones. However, several SNP applications
      were needed to improve the impaired CoBF, while a single portion was sufficient
      in the normal cochlea to cause a drastic increase in mean CoBF to 234% of
      baseline. In urethane-anesthetized animals, no flow increase was found despite
      repeated drug administration. Careful evaluation of the laser Doppler signals was
      necessary to accurately determine the concentrations of the moving blood cells
      and their mean velocities.

PMID- 9783127
TI  - Taurine entry into perilymph of the guinea pig.
AB  - Taurine is a beta-aminosulfonic acid and is a ubiquitous amino acid whose role in
      the cochlea is not well established. In this study, its entry from blood into
      perilymph was investigated in the guinea pig as animal model. The penetration
      rate of [3H]taurine (molecular weight 125) into the perilymph of the scala
      vestibuli was measured 1 and 2 h after the intravenous infusion of [3H]taurine in
      nephrectomized animals. Results showed a rate of penetration in perilymph related
      to plasma at 36 +/- 4.7% (n = 5) after 1 h and 43 +/- 5.6% (n = 5) after 2 h.
      Compared to the penetration rate of urea (molecular weight 60) and mannitol
      (molecular weight 186) reported previously in rats, a passive entry of taurine
      into perilymph through the blood-perilymph barrier is suggested.

PMID- 9783129
TI  - Use of electron spectroscopic imaging to determine element composition of the
      melanin granules in the stria vascularis of the guinea pig.
AB  - Electron spectroscopic imaging (ESI) was used to analyze the element content of
      melanin granules in the stria vascularis seen in ultrathin sections of Spurr
      embedded cochleae of the guinea pig. To determine element composition, ESI images
      were taken at different ionization edges, and non-specific background signals
      were subtracted digitally by an image processing system. The presence of calcium
      and nitrogen in the melanin granules could be demonstrated clearly. The calcium
      identified in the melanin granules was then compared with the spatial
      distributions of calcium binding sites after the application of an antimonate
      precipitation method, which was used to localize loosely bound calcium. Despite a
      high calcium concentration within the granules, only very small single scattered
      calcium precipitates could be detected between these structures as compared with
      the amount of calcium precipitates attached to the plasma membrane or located
      within the cell nuclei. The nearly complete absence of precipitates within the
      melanin granules after the application of antimonate suggests differences in
      calcium binding and mobility involved in various physiological processes of ion
      balance regulation within the stria vascularis.

PMID- 9783131
TI  - Facial nerve stimulation by a cochlear implant in a hemodialysis patient with
      bone of low mineral density.
AB  - Facial nerve stimulation by an activated cochlear implant was noted in a 56-year
      old patient who had undergone cochlear implant with a Nucleus 22 implant 2 years
      previously as treatment for total sensorineural hearing loss following meningitis
      at age 54. Past history was complicated by total renal failure for which
      hemodialysis had been required during the past 13 years. Facial spasm occurred 5
      months postoperatively with activation of the basal electrodes (channels 13 and
      15 of the implant). The facial stimulation was eliminated by deprogramming these
      electrodes. High-resolusion computed tomography (CT) scanning was unable to
      demonstrate lucency of the otic capsule and cochlear ossification, but basal
      electrodes of the implant could be identified near the labyrinthine segment of
      the facial nerve. To further evaluate bone changes in the patient, the total and
      regional bone mineral density (BMD) of the head and radius was measured by dual
      energy X-ray absorptiometry. All BMD values of the patient were markedly low when
      compared to those of 62 other hemodialysis patient. These findings demonstrate
      that facial nerve stimulation can occur in the presence of low impedance due to
      cortical bone changes induced by long-term hemodialysis.

PMID- 9783130
TI  - A molecular epidemiologic study of methicillin-resistant Staphylococcus aureus
      infection in patients undergoing middle ear surgery.
AB  - The incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections
      after middle ear surgery has recently increased at our hospital. Most of these
      infections were thought to be hospital-acquired when medical personnel in contact
      with an MRSA-infected patient may have inadvertently transmitted the pathogen to
      other patients. To prevent further transmission it is essential that such sources
      of MRSA infection and transmission routes be selected out and eradicated.
      Therefore, it is necessary to determine whether the strains of MRSA isolated from
      infected patients are identical to those obtained from medical personnel in order
      to prove a reciprocal transmission of organisms between medical personnel and
      patients. Surveillance bacterial cultures from the anterior nares and hands of
      medical personnel working in the Department of Otolaryngology, Korea University
      Guro Hospital, were performed at two different time points: 6 December 1994 and
      17 June 1996. Ribotyping with Southern blot technique was used to compare 12 MRSA
      strains from medical carriers with 60 strains identified from the otorrhea of
      MRSA-infected patients undergoing middle ear surgery. As results, six different
      MRSA strains were identified (types I, II, III, IV, V and VI) from ribotyping
      with EcoR1. One distinct subtype, type I strain, was the most frequently
      identified strain in both medical carriers and patients. Results also showed that
      6 MRSA isolates from 10 medical carriers and 20 from 30 patients contained type I
      ribotype at first culture. Two medical carriers' isolates and 13 isolates from 30
      patients shared the same type I strain at the second surveillance culture. In
      all, 41 out of 72 MRSA strains (56.9%) shared an identical ribotype pattern.
      Postoperative MRSA infection rates after treatment of medical carriers and the
      application of rigorous preventive procedures decreased from 11.9 to 5.7% after
      first culture and 9.0 to 7.7% following second cultures. These findings confirm
      that MRSA transmission can occur between medical personnel and patients and that
      effective preventive measures can reduce the postoperative infection rate.

PMID- 9783132
TI  - Clinical validation of a new olfactory test.
AB  - A new approach to clinical olfactometry is presented using nasal sprays. A
      special dosage valve was used to standardize an aerosol size to 40 microns. For
      evaluation a 6 x 6 matrix (substance/olfactory quality) with verbal associative
      clues was used according to test psychological findings. Validation took place in
      three steps after determining smell-associated thresholds in preliminary
      examinations. Recognition of different aromas administered either by spraying
      into the open mouth from a distance of 5 cm using nasal sprays or sniffing opened
      bottles was compared in 50 subjectively normosmic subjects. Findings showed that
      the correspondence between the two procedures was relatively high, with global
      identification of odorous substances as high as 98.4% in the spray test. The
      number of substances used was next reduced to those six substances providing the
      most reproducible results in an investigation with 56 normosmic and 55 hyposmic
      subjects. Verbal associative clues were also tested. In a last step 50 patients
      with hyposmia of various origin and 110 normosmic subjects were tested, allowing
      previous results to be reproduced regardless of the cause of hyposmia. The spray
      test was shown to be easily performed and was suitable as a screening test, with
      a sensitivity of 88% and a specificity of 100%.

PMID- 9783133
TI  - The ex vivo effect of the herbal medicine sho-saiko-to on histamine release from
      rat mast cells.
AB  - A traditional Japanese herbal medicine, Shosaiko-to (SST), has been used orally
      to treat several chronic diseases. Since these have included allergic rhinitis
      and bronchial asthma, we investigated the effect of SST on histamine release and
      the intracellular Ca2+ response in mast cells ex vivo. A single dose of 1.0 g/kg
      SST was administered orally to immunized rats 2-12 h before death. Mast cells
      were then separated from peritoneal lavages and stimulated with antigen. SST at 3
      h after oral administration most significantly inhibited histamine release. This
      inhibitory effect was dose-dependent and was weaker than that of tranilast. In
      contrast, SST at 3 h had no effect on the antigen-induced Ca2+ response of the
      mast cells and failed to inhibit compound 48/80-induced histamine release. Our
      findings show that SST indeed has an active anti-allergic effect. We suggest that
      SST inhibits IgE receptor-associated protein phosphorylation in the histamine
      release pathway.

PMID- 9783134
TI  - The muscular tissue of the vestibular folds of the larynx.
AB  - The muscular tissue of the vestibular folds was investigated in plastinated
      serial sections of 32 normal adult larynges. Three muscular systems could be
      distinguished. A posterolateral muscle layer was found to be developed at the
      lateral margin of the posterior part of the vestibular fold. Its fibers extended
      in a sagittal direction, and their contraction probably resulted in an adduction
      of the entire tissue of the vestibular fold towards the midline. Within the
      anterior part of the vestibular fold, an anterolateral muscle sheet was seen to
      attach to the thyroid cartilage. An anteromedial muscular system consisted of
      scattered groups of muscle fibers situated medially and dorsally to the laryngeal
      ventricle and saccule. These fibers were presumed to exert a downward pressure on
      the vestibular folds, in addition to an adductor function. According to clinical
      experience, adductor movements of the vestibular folds can be trained, even in
      cases with a recurrent laryngeal nerve lesion, in order to produce a compensatory
      voice. Thus, the muscles of the vestibular folds are probably innervated by the
      superior laryngeal nerve.

PMID- 9783135
TI  - Malignant lymphoma of mucosa-associated lymphoid tissue in the larynx.
AB  - A 36-year-old woman was referred to the department of Otolaryngology/Head and
      Neck Surgery, University Hospital Vrije Universiteit, because of complaints of
      hoarseness. A submucosal swelling of the right ventricular fold was found that
      was subsequently biopsied. Histopathological examination showed a low-grade B
      cell non-Hodgkin's lymphoma of mucosa-associated lymphoid tissue (MALT).
      Treatment consisted of local radiotherapy (to 2800 cGy). During the 2-year follow
      up to date there has been no evidence of recurrent disease. To our knowledge,
      only four cases of MALT lymphomas in the larynx have been reported. The clinical
      behavior of MALT lymphoma is clearly quite distinct and requires proper
      recognition to prevent inadvertent misdiagnosis of overtreatment.

PMID- 9783136
TI  - Evaluation of voice and speech following subtotal reconstructive laryngectomy.
AB  - Subtotal reconstructive laryngectomy (SRL) can be used to preserve voice in the
      treatment of selected laryngeal carcinomas. This study was designed to analyze
      both voice and speech results achieved after SRL in 14 male patients, aged from
      48 to 73 years. Surgery was performed between 1983 and 1993. Fundamental
      frequencies, ranges of frequency, intensities, and intensity ranges were
      established using an S.I. 80 Philips AAC 600 Audio Active Comparative Language
      System. Five prolonged vowels and six phonetically balanced sentences were
      recorded on a tape positioned at a distance of 30 cm from the mouth of each
      patient during a 3-min recording time. The recorded material was then evaluated
      by a panel of ten trained listeners who were asked to consider the qualitative
      parameters and perceptual characteristics of voice and speech according to a
      scorecard modified from one devised by Voiers and Formigoni. Although a decrease
      was determined in Fundamental Frequency and intensity of the voice when compared
      to normal values, the quality and perception of speech were found to be
      satisfactory. The verbal message could be understood almost exactly by means of
      constant sonority, correct articulation and improved pneumophonic coordination.
      These values demonstrate that the new voice achieved after SRL is less sonorous
      and allows for understandable and socially acceptable speech.

PMID- 9783137
TI  - Vocal cord laterofixation as early treatment for acute bilateral abductor
      paralysis after thyroid surgery.
AB  - Bilateral vocal cord palsy due to a lesion of the recurrent laryngeal nerves is a
      serious complication of thyroid operations, with the airway obstruction usually
      necessitating tracheostomy. In the cases presented, a stable airway was ensured
      with endolaryngeal cord laterofixation instead of tracheostomy. The operation was
      performed with the endo-extralaryngeal needle carrier instrument devised by
      Lichtenberger. During the operation, only minor surgical trauma occurred in the
      larynx. The fixing thread was then removed following recovery of contralateral
      vocal cord function, resulting in an improvement in the voice. Four patients are
      described who suffered bilateral recurrent laryngeal nerve palsy after thyroid
      gland operations. During the follow-up period of 3-12 months, airway stability
      was demonstrated by regular spirometric measurements. The simple method
      recommended spares patients the possible complications of tracheostomy.

PMID- 9783138
TI  - Pharyngeal localizations of branchial cysts.
AB  - Two cases with unusual pharyngeal localizations of branchial cysts medial to the
      great neck vessels and pharyngeal constrictor muscle are presented. The authors
      reviewed the theories of origin of the branchial cysts and the surgical treatment
      options. In their first case the transoral approach was chosen. Because of
      previous unsuccessful attempts at surgical treatment, the pharyngeal cyst was
      extremely adherent to adjacent tissue with much scar tissue, and it was very
      difficult to remove. As a result of this disappointing operation, an external
      neck exploration was indicated in the second patient. Histological examinations
      confirmed that the excised cysts were branchial in both cases.

PMID- 9783139
TI  - Brain abscess with fatal intraventricular rupture caused by asymptomatic
      paranasal sinusitis.

PMID- 9783140
TI  - Formation of spheroidal aggregates of hepatocytes on biodegradable polymers under
      continuous-flow bioreactor conditions.
AB  - Our laboratory has investigated heterotopic hepatocyte transplantation on
      biodegradable polymer matrices as an experimental treatment for end-stage liver
      disease. One of the limitations has been survival of sufficient cell mass after
      transplantation. We hypothesize that in vitro conditioning of cells within
      polymer matrices prior to implantation may increase hepatocyte survival and
      function. In this preliminary study we investigated the effect of continuous flow
      on hepatocytes and sinusoidal endothelial cells on poly-L-lactic acid (PLLA)
      discs in vitro. Highly porous PLLA discs were manufactured measuring 18 mm
      diameter by 1 mm thickness using previously described techniques. Hepatocytes
      were isolated from adult, male Lewis rats (200-300 g) using a two-step
      collagenase digestion. Sinusoidal endothelial cells were isolated using a two
      step collagenase digestion, differential sedimentation, Percoll gradient
      centrifugation, and selective adherence. PLLA discs were seeded with hepatocytes
      alone or with co-cultures of hepatocytes and sinusoidal endothelial cells. Seeded
      discs were then secured within a flow bioreactor chamber and exposed to
      continuous flow of culture media at a rate of 20 ml/minute through the chamber.
      Seeded discs placed in static culture conditions served as controls. Specimens
      seeded with only hepatocytes were harvested at 24 hours, 48 hours, and 168 hours
      after seeding. Co-culture specimens were harvested after 168 hours. Specimens
      were viewed under phase-contrast microscopy and then formalin-fixed and prepared
      for histologic sectioning. Sections were stained with Hematoxylin and Eosin and
      then analyzed with light microscopy. Hepatocytes under flow conditions formed
      spheroidal aggregates of cells of 50 to 200 microns in diameter by 24 hours in
      culture. Hepatocytes in static conditions showed decreased aggregation of cells
      and spheroid formation was absent. Co-cultured specimens under flow also showed
      spheroid formation with endothelial cells lining the outside of hepatocyte
      spheroids. Co-cultured specimens in static culture showed no spheroid formation
      and no organization between sinusoidal endothelial cells and hepatocytes. These
      results suggest that continuous flow increases organization of hepatocytes
      cultured within biodegradable polymer matrices.

PMID- 9783141
TI  - Quantitative assessment of intracranial pressure by the tympanic membrane
      displacement audiometric technique in children with shunted hydrocephalus.
AB  - The objective of this prospective study was to compare the clinical features at
      presentation, tympanic membrane displacement test results and direct intracranial
      pressure measurements in children with shunted hydrocephalus to procure a
      quantitative measure of the intracranial pressure by tympanic membrane
      displacement test. A prospective comparative evaluation of 61 clinical episodes
      of shunt malfunction was assessed by volume displacement of the tympanic membrane
      and direct intracranial pressure measurements in 40 patients with shunted
      hydrocephalus between January 1995 and June 1996. The volume displacement of the
      tympanic membrane (Vm) on stapedial contraction was inward for raised
      intracranial pressure in 27 episodes and ranged from -120 nl to -506 nl (mean = 
      250 nl). This was confirmed by direct intracranial pressure monitoring, which
      ranged from 23 to 40 mm Hg (mean = 29 mm Hg). The tympanic membrane displacement
      test measurement in 30 episodes of low intracranial pressure ranged from +263 nl
      to +810 nl (mean = +530 nl), and this was corroborated by direct intracranial
      pressure measurement ranging from 1 to 6 mm Hg (mean = 3.8 mm Hg). The normal
      baseline Vm values obtained when the subjects were asymptomatic ranged from +58
      nl to +175 nl (mean = +115 nl). The tympanic membrane displacement test as a non
      invasive diagnostic tool in predicting changes in intracranial pressure had a
      sensitivity of 93% and specificity of 100%. The predictive value of the test was
      100%, and the negative predictive value was 73%. The kappa statistical analysis
      was used to measure the agreements between the groups. The strength of the
      agreement was very good, kappa = 0.88 and the P value was < 0.001. The objective
      measure of intracranial pressure by tympanic membrane displacement test with the
      Vm value of -200 nl and more negative was indicative of raised intracranial
      pressure and a Vm value of +200 nl and greater, for low intracranial pressure.
      The intracranial pressure measurements made on an individual subject basis were
      reliable and accurate. The test can therefore be used for regular assessment of
      shunted hydrocephalics to enable correlation of intracranial pressure with
      symptoms in individual patients.

PMID- 9783142
TI  - Lung transplantation for cystic fibrosis.
AB  - Between November 1996 and November 1997 we have transplanted 13 patients with
      Cystic Fibrosis (CF). Bilateral Sequential Lung Transplantation (BSLT) was
      successfully performed in all patients; one patient died from pneumonia and
      sepsis in the postoperative period and 12 are alive and well after a follow-up
      ranging between 1 and 13 months. Blood gas analysis improved from mean values of
      PaO2: 56 mm/Hg (with oxygen) and PaCO2: 43 mm/Hg to mean values of PaO2: 85 mm/Hg
      and PaCO2: 37 mm/Hg. Pulmonary function tests also improved dramatically: FEV1
      improved from 20% predicted to 98% predicted. FVC also improved from 39% to 100%.
      The quality of life markedly improved: the ideal body weight moved from about 84%
      to normal values within nine months, and the 6-minute walk-test improved after
      transplantation from a preoperative distance of 325 meters, to 600 meters after 6
      months. In conclusion, our favorable experience with BSLT in CF patients
      emphasizes the importance of lung transplantation in these patients. Carefully
      selected and properly managed patients may benefit from transplantation in terms
      of quality and duration of life.

PMID- 9783143
TI  - Murine duodenum does not go through a "solid core" stage in its embryological
      development.
AB  - Embryological development of duodenum is believed to go through a "solid core"
      stage which subsequently vacuolizes. Failure of vacuolization is thought to be
      the cause of duodenal atresia. This study examines the embryological development
      of rat duodenum. Thirty-six time-mated Sprague-Dawley rats were studied. Six
      fetal duodenal specimens were obtained for each gestational day from day 9 to day
      20. These specimens were fixed with formalin, sectioned, stained with
      haematoxylin and eosin and examined under microscope. The duodenal diameters and
      the lumen diameters at each gestational date were measured. The foregut started
      to form at the gestation stage of day 10. The lumen was narrowest on days 12 and
      13, but the duodenum did not become a "solid core". No vacuolization was detected
      through out the development of the duodenum. Embryological development of rat
      duodenum did not go through a "solid core" stage.

PMID- 9783144
TI  - Cerebral ischemia reperfusion-induced vasogenic brain edema formation in rats:
      effect of an intracellular histamine receptor antagonist.
AB  - Resuscitation in pediatric emergency and some neurological interventions may
      result in ischemia reperfusion-induced cerebral injuries. Histamine is one of the
      well established mediators of cerebral swelling and H1- and H2-receptor
      antagonists could prevent the development of ischemic brain edema. In the present
      study, time-dependent changes in the blood-brain barrier (BBB) permeability were
      investigated in the cerebral cortex of male Wistar rats 1, 2, 4, 8, and 16 h
      after the beginning of post-ischemic reperfusion. Cerebral ischemia-reperfusion
      evoked by the 4-vessel occlusion model resulted in significant (p < 0.05)
      elevations in BBB permeability for albumin, but not for sodium fluorescein. Pre
      treatment with a new intracellular histamine receptor antagonist could not
      prevent ischemic brain edema formation in that model. We conclude that
      experimental studies could help us to reveal the therapeutic role of histamine
      receptor antagonists during ischemic brain edema.

PMID- 9783145
TI  - First clinical evaluation of a new concept for puncture-site occlusion in
      interventional cardiology and angioplasty.
AB  - Percutaneous transluminal angioplasties of coronary and peripheral vessels are
      frequently used and replace open surgery in a certain percentage. Hemostasis in
      most of these patients is reduced or inhibited and often leads to hemorrhage from
      the puncture track. Due to this fact, hospitalization is not only mandatory, but
      also surgical revision of the puncture site is often required. We designed and
      produced a coaxial delivery system, which is mounted on the indwelling guide-wire
      after withdrawal of the instrumentation for angioplasty. The delivery system is
      advanced down to the outer wall of the punctured vessel and 1 cc of human two
      compound fibrin glue is released. Based on our experience with laboratory and
      animal research, which we already presented at the 7th International Symposium on
      Pediatric Surgical Research in Heidelberg, May 27-28, 1994, we conducted the
      first trials in interventional cardiology. In 1996, a first group of 10 patients,
      aged 49 to 80 years, underwent sealing of the right femoral artery after
      diagnostic evaluation (n = 3) of coronary balloon dilatation (n = 7). In
      patients, the local manual compression time was less than 5 minutes and 1 patient
      needed 10 minutes of digital compression. In one case, bleeding continued and a
      compression bandage was successful, whereas in another case the local hematoma
      formation needed surgical revision with suture of the ruptured vessel wall.
      CONCLUSION: Puncture-track sealing with locally applied fibrin glue seems to be
      an efficient tool to avoid bleeding after interventions of coronary and
      peripheral vessels. In the meantime, the device has been improved by a target
      system to optimize the delivery of the glue exactly at the outer wall of the
      vessel.

PMID- 9783146
TI  - Does hepatocyte transplantation in a chemically induced acute hepatic failure
      make sense?
AB  - PURPOSE: Acute hepatic insufficiency (AHF) is one of the major challenges of
      intensive care medicine. Liver transplantation is the current solution to
      unsuccessful medical management. Owing to the lack of organ donors, other methods
      such as hepatocyte transplantation (HcTX) and bioartificial livers need to be
      explored. The aim of our experimental study is to evaluate the effect of
      hepatocyte transplantation on the survival in AHF animals intoxicated with D
      Galactosamine (D-Gal). METHODS: The first step consists of the determination of
      the dose of D-Gal needed to induce at least 80% mortality between 48 and 72
      hours. Two groups of a single strain of male Wistar rats are then compared, one
      being intoxicated with D-Gal (control group), the other receiving and HcTX in the
      splenic parenchyma 48 hours after intoxication. RESULTS: The required dose to
      achieve AHF is 3 gr/kg body weight (Gr. 0). Survival rates are as follow: Gr. 1:
      D0: 93%; from D1 to D28: 13%. Gr. 2: D0: 80%; D1 and D2: 33%; D3: 20%; D4: 13%,
      from D5 to D28: 6%. (D0 = Day of transplantation). Liver enzymes show a peak of
      deterioration at 24 hours, then return to normal values in both groups.
      Histological examination of those animals still alive and sacrificed on day 28
      demonstrates a restitutio ad integrum of hepatic structure. In Group 2, it is
      possible to observe remaining living hepatocytes in the splenic parenchyma.
      CONCLUSIONS: When HcTX is performed 48 hours after D-Gal intoxication, i.e., when
      the animals begin to develop AHF symptoms, animal survival only significantly
      improves between days 0 and 3. Unlike other trials, we cannot demonstrate an
      improvement in long-term survival. Thus, according to this particular
      experimental model, HcTX is not an alternative for the treatment of AHF.

PMID- 9783148
TI  - Functional and morphological examination of ganglionic and aganglionic distal gut
      from the lethal spotted mouse.
AB  - The aim of the study was to evaluate both morphologically and functionally the
      distal large intestine from the aganglionic lethal spotted (ls/ls) mutant mouse
      and their healthy litter mates. Immunohistochemically, the aganglionic murine
      distal large intestine showed an absence of nerve cell bodies, and a reduction or
      absence of nerve fibers displaying immunoreactivity (IR) for protein gene product
      (PGP), nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP),
      substance P (SP), galanin and calcitonin gene-related peptide (CGRP), while in
      the ganglionic large intestine these neuronal populations were abundantly present
      throughout the gut wall. Pathological nerve trunks within the afflicted
      intestinal segment were found to harbour PGP- and neuropeptide Y (NPY)-IR nerve
      fibers. Smooth muscle specimens from the distal part of the murine distal large
      intestine were mounted as ring preparations in vitro and subjected to electrical
      field stimulation (EFS). EFS (4-20 Hz) caused a contraction in both ganglionic
      and aganglionic intestine. After pretreatment with atropine EFS (20 Hz) evoked a
      biphasic motor response, a relaxation followed by a contraction in control
      specimens, while no motor response was seen in aganglionic intestine. Addition of
      the NOS-inhibitor N-nitro-L-arginine methyl ester (L-NAME) caused per se a weak
      and transient contraction and reduced the amplitude of the EFS-induced relaxation
      in control intestine.

PMID- 9783147
TI  - Autogenic allotopic small-bowel mucosa transplantation in beagles. A new
      perspective for treatment of small-bowel syndrome?
AB  - There is no standard treatment for the short-bowel syndrome. The aims of surgical
      therapy are based on: slowing the intestinal transit, increasing the absorbing
      intestinal area and small-bowel transplantation. Searching for a new surgical
      treatment we developed an alternative for increasing the absorbing small-bowel
      area by means of autogenic allotopic small-bowel mucosa transplantation in beagle
      dogs. In young animals we isolated the transverse colon leaving the blood supply
      intact. Colonic continuity was reestablished and two abdominal stomata were
      performed at the ends of the isolated transverse colon. A week thereafter the
      colonic mucosa of the isolated transverse colon was surgically removed and
      autologous small-bowel mucosa was transplanted in the demucosed colon. The
      animals were then sacrificed 2, 4 and 6 weeks after transplantation and the colon
      coat-ileal-mucosa complex (CIC) was histologically examined. The ileal mucosa
      could be transplanted in the demucosed colon showing histological characteristics
      of ileal mucosa. The circular muscle of the colon coat developed a hypertrophy
      which was present even 6 weeks after transplantation. In this study we could show
      that autogenic allotopic small-bowel mucosa transplantation is feasible in beagle
      dogs and may prove a novel method of small bowel expansion in cases of small
      bowel syndrome.

PMID- 9783149
TI  - Cryopreservation and transplantation of fetal adrenal glands in adrenalectomized
      rats.
AB  - In a syngeneic rat model, the present study investigated the cryobiology of fetal
      adrenal glands and compared the endocrinological function of cryopreserved versus
      fresh fetal adrenal transplants in the adrenalectomized hosts. Ultrastructural
      studies showed no significant tissue damage by the cryopreserving technique:
      cellular membranes were intact, the mitochondria showed discrete swelling and
      vacuoles were found in the endoplasmatic reticulum. Following transplantation,
      maturation and bilateral adrenalectomy in the host, assessment of
      endocrinological parameters demonstrated that survival was prolonged and Addison
      crisis could be prevented in both transplant groups with no significant
      difference between fresh versus cryopreserved grafts. To our knowledge this study
      presents the first morphological and endocrinological data about the successful
      transplantation of cryopreserved fetal adrenal glands in rats. In conclusion,
      cryopreservation is tolerated well by the tissue and long-term banking may
      therefore contribute to the feasibility and benefit of fetal adrenal
      transplantation. However, further investigations will be necessary to evaluate
      fetal adrenal transplantation in an allogeneic and xenogeneic setting.

PMID- 9783150
TI  - Changes of urinary enzyme activity after endoscopic treatment of vesico-ureteric
      reflux.
AB  - The urinary enzymes Gamma Glutamyl Transferase (GGT), Alkaline Phosphatase (ALP),
      Leucine-Arylamidase (LAS), and Dipeptidyl-Peptidase-IV (DPP-IV) were measured
      before and after endoscopic treatment of vesico-ureteric reflux (VUR) in two
      groups of twenty children. Ten patients had undergone successful endoscopic
      corrective surgery for VUR, another 10 patients had unsuccessful endoscopic
      intervention. After successful treatment the activity of LAS in the urine did not
      change, but GGT, ALP and DPP-IV activity in the urine was 2-5 times higher than
      before treatment (P < 0.03 for all three enzymes). Considerable changes of
      urinary enzyme activity were not observed following unsuccessful endoscopic
      treatment. Our data and the literature are contradictory. However, this
      contradiction might be explained by the differences in urine sampling methods.
      Our patients received the same chemoprophylactic drug at the time of both urine
      samplings, a point not considered by other researchers. The extent of increase of
      enzyme activity after endoscopic treatment of VUR did not reach the level that
      would permit the use of investigated enzymes for screening, because the observed
      changes did not exceed the limits of the normal range.

PMID- 9783151
TI  - Bacterial translocation and T-lymphocyte populations in experimental short-bowel
      syndrome.
AB  - Bacterial translocation (BT) accounts in part for sepsis in short-bowel syndrome
      in which total parenteral nutrition (TPN) is routinely necessary. TPN "per se"
      facilitates BT and it has been suggested that decreased T-lymphocyte populations
      (TLP) in newborn rabbits and nude mice promote BT as well. We have tested the
      hypothesis that BT and modifications in TLP are to be expected in rats subjected
      to TPN and gut resection. Forty-five adult Wistar rats underwent central venous
      cannulations and were randomly assigned to one of three groups receiving for ten
      days three treatment regimes: - Group Sham (n = 17) oral intake of rat chow +
      saline (300 ml/kg/24 h) through a jugular vein catheter. - Group TPN (n = 17)
      fasting + infusion of all-in-one TPN solution (300 ml/kg/24 h). - Group RES (n =
      11) fasting, same TPN regime + 80% gut resection. At the end of the experiment
      they were sacrified and specimens (peripheral and portal blood, spleen and
      mesenteric lymph nodes) were recovered, cultured and/or assessed for CD4+ and
      CD8+. Bacterial translocation was found in 47% of TPN animals, 92% of RES rats,
      but not in SHAM ones. Lymphocyte populations were not different in BT+ (n = 8) or
      BT- (n = 9) rats in the TPN group. TPN and resected animals showed a rise in CD4+
      and a drop in CD8+ (then a better CD4+/CD8 ratio) when comparing with SHAM group
      rats. From this data we may conclude that: 1) BT is frequent if TPN is
      administered, and constant in resected animals. 2) No apparent relationship
      between the proportions of CD4+ and CD8+ lymphocytes and BT could be shown in TPN
      group. 3) High CD4+/CD8+ ratio in TPN and RES groups demonstrate that BT is
      possible even having good TLP.

PMID- 9783152
TI  - Stimulation of fracture healing by local application of humoral factors
      integrated in biodegradable implants.
AB  - Growth stimulation by growth hormones or by IGF-1 is well known whereas
      publications about stimulation of fracture healing with these substances are
      rare. One of the main effects of IGF-1 is angiopoiesis which consequently may be
      expected to induce and accelerate the soft tissue callus formation. BMP-2 is a
      stimulator for osteoclasts and osteoblasts and prepares the osseous reparation.
      RhBMPs, mostly BMP-2, are already used in the reconstruction of the cranial
      vault. The main disadvantage of these proteins is the quick inactivation after
      about 20-30 minutes. Local stimulation without systemic effects might be avoided
      by releasing a low but constant dose of IGF-1 or BMP. We speculate that the
      combination of a reasonable implant with an integrated drug release system may
      enlarge the field of application of biodegradable implants in the treatment of
      fractures. Such an implant might remarkably reduce the time for fracture healing
      and also lower the costs of postoperative treatment. In this paper we report our
      animal models in which we have tested constructive principles of biodegradable
      implants, we present the first clinical experiences with polyactates (PLLA) in
      the osteosynthesis of children, and we describe our inventions concerning drug
      releasing implants. 1) PLLA-implants a) The animal models We performed on oblique
      osteotomy of the right metacarpal bone in 48 juvenile calves and osteoplastic
      reconstructions of the cranial vault in 28 juvenile Gottinger minipigs.
      Biodegradable osteosynthesis with PLLA implants led to results as good as with
      conventional materials in both animal models, so that we proceeded to clinical
      evaluation in children. b) The clinical application in children 35 children, aged
      6 weeks to 17 years, had resorbable osteosynthesis of their cranioplasties for
      correction of congenital malformations and posttraumatic reconstructions. The
      follow-up ranged from 5-15 years. 2) Invention of a drug-releasing system IGF-1
      or BMP-2 is planned to be incapsulated by evaporation technique into nanospheres
      of low PDLLA (Poly-DL-Lactite) with a molecular weight of about 20,000 and an
      expected resorption time of 2-3 weeks (patent pending). 3) Concept of our drug
      releasing resorbable implants Plates could be built up in multilayers of PDLLA
      sheets, separated by a spongiform matrix containing the IGF-1- or BMP-2-loaded
      nanospheres. The screws are hollow due to an internal driving system. The
      specially designed thread could also contain nanospheres, which would be brought
      into the cortical bone and the medullary space. The cavity of the screw is filled
      up with nanospheres after tightening.

PMID- 9783153
TI  - Age differences in entropy: primary versus secondary memory.
AB  - We report a spatial-memory scanning experiment that was used to measure age
      differences in entropy. A target grid consisting of four adjacent letters
      followed by the presentation of a single probe letter was presented on each
      trial. Half of the trials presented the probe stimulus in the same spatial
      position was the target letter (i.e., the probe letter was always a member of the
      positive set), and half of the trials transposed the target letter one, two, or
      three spaces of the right or left of the original target display position (i.e.,
      different trials). The experiment involved blocks of primary-memory and secondary
      memory tasks. Reaction-time and error-rate data, as well as entropy analyses and
      the fitting of an entropy model (based on Allen, Kaufman, Smith, and Propper, in
      press) to the empirical data indicated that older adults showed higher entropy
      levels than young adults. These results are interpreted in a "computational
      temperature" framework in which older adults' higher computational temperatures
      result in less efficient spatial, episodic memory functioning.

PMID- 9783154
TI  - Age, target-distractor similarity, and visual search.
AB  - Younger and older adults were asked to find a single target in both feature- and
      conjunction- search conditions. Display size varied between 2 and 8 items, and
      target-distractor similarity ranged from relatively low to high levels. The
      accuracy data indicated that older adults had particular difficulty finding
      targets in high-similarity conjunction-search displays containing a large number
      of distractors. The reaction time (RT) analyses found larger age deficits in many
      of these same conditions. For both groups, predictions of conjunction search
      based on Treisman and Sato's additive model (Journal of Experimental Psychology:
      Human Perception and Performance, 1990: 16, 459-478) departed significantly from
      actual performance. The RT data of older observers were, in large part, predicted
      as a simple linear function of the young adults' data. These results are
      discussed with respect to age differences in selective attention, generalized
      slowing, and an age-related loss in search efficiency.

PMID- 9783155
TI  - Verbal and figural recognition memory: task development and age associations.
AB  - The goal of the present study was to develop and validate parallel tests of
      verbal and figural delayed-recognition memory with similar task demands and
      difficulty levels. Such tasks would allow examination of age differences and
      longitudinal age changes in visual recognition memory for two types of stimuli,
      activate divergent neural systems, and allow us to use the same procedures within
      the confines of functional neuroimaging as those we use in standard
      neuropsychological administration. The tasks introduced here include a delay
      between target presentation and test phase, are matched in difficulty, and yield
      moderate levels of performance. Individual and group differences in task
      performance were examined in 80 cognitively normal men and women in two older age
      groups: 60 to 69 and 70 to 85. Accuracy averaged 74% in both tasks, with lower
      performance in the oldest age group. Although accuracy was equivalent between
      tasks, subjects had a more liberal response bias in the figural than verbal task.
      Performance on the new recognition-memory tests was significantly related to
      Benton Visual Retention Test (BVRT; Benton [1963]. New York: The Psychological
      Corporation) and California Verbal Learning Test (CVLT; Delis, Kramer, Kaplan, &
      Ober [1987]. New York: The Psychological Corporation) performance measures. The
      absence of floor or ceiling effects, wide range of individual variability, and
      demonstrated concurrent validity of the present tasks suggest their potential
      utility in functional neuroimaging studies and in the early detection of
      cognitive decline.

PMID- 9783156
TI  - Conditioned-reflex facilitation in young and older adults.
AB  - Young (18-30 years) and elderly (63-88 years) human subjects received 70 trials
      of single-cue classical eyeblink conditioning (paired group), or 70 explicitly
      unpaired presentations of the tone conditioned stimulus (CS) and airpuff
      unconditioned stimulus (unpaired group). Before and after conditioning, reflex
      eliciting white noise and corneal airpuff stimuli were presented alone or paired
      with the CS to investigate the effects of conditioning on eyeblink reflex
      amplitude. The results showed increased conditioned responses in the paired group
      compared to the unpaired group for the young but not the elderly subjects. There
      was, however, evidence of conditioned facilitation of noise-elicited reflexes in
      both young and elderly subjects. These data indicate that conditioned
      facilitation of the startle reflex may be a sensitive indicator of classical
      conditioning processes in human subjects.

PMID- 9783157
TI  - Genetic elements in the extremely thermophilic archaeon Sulfolobus.
AB  - This minireview summarizes what is known about genetic elements in the archaeal
      crenarchaeotal genus Sulfolobus, including recent work on viruses, cryptic
      plasmids, a novel type of virus satellite plasmids or satellite viruses, and
      conjugative plasmids (CPs), mostly from our laboratory. It does not discuss IS
      elements and transposons.

PMID- 9783158
TI  - Histones and nucleosomes in Archaea and Eukarya: a comparative analysis.
AB  - Archaeal histones from mesophilic, thermophilic, and hyperthermophilic members of
      the Euryarchaeota have primary sequences, the histone fold, tertiary structures,
      and dimer formation in common with the eukaryal nucleosome core histones H2A,
      H2B, H3, and H4. Archaeal histones form nucleoprotein complexes in vitro and in
      vivo, designated archaeal nucleosomes, that contain histone tetramers and protect
      approximately 60 base pairs of DNA from nuclease digestion. Based on the sequence
      and structural homologies and experimental data reviewed here, archaeal
      nucleosomes appear similar, and may be homologous in evolutionary terms and
      function, to the structure at the center of the eukaryal nucleosome formed by the
      histone (H3 + H4)2 tetramer.

PMID- 9783159
TI  - Mechanisms of gene expression controlled by pressure in deep-sea microorganisms.
AB  - A pressure-regulated operon has been cloned and sequenced from deep-sea
      barophilic Shewanella strains. To understand pressure-regulated mechanisms of
      gene expression, a regulatory element upstream of the pressure-regulated operon
      from Shewanella sp. strain DSS12 was studied. Regions A and B were classified by
      sequence analysis. A unique octamer motif, AAGGTAAG, was found to be repeated in
      tandem 13 times in region B. An electrophoretic mobility shift assay demonstrated
      that a O54-like factor recognizes region A and other unknown factors recognize
      region B. Different shift patterns of the protein-DNA complexes were observed
      when extracts of cells cultured at 0.1 MPa or 50 MPa were incubated with a DNA
      probe specific for region B. These results indicate that the deep-sea strain
      DSS12 expresses different DNA-binding factors under different pressure
      conditions.

PMID- 9783160
TI  - Molecular phylogenetic identification of the intestinal anaerobic microbial
      community in the hindgut of the termite, Reticulitermes speratus, without
      cultivation.
AB  - A termite maintains an anaerobic microbial community in its hindgut, which seems
      to be the minimum size of an anaerobic habitat. This microbial community consists
      of bacteria and various anaerobic flagellates, and it is established that
      termites are totally dependent on the microbes for the utilization of their food.
      The molecular phylogenetic diversity of the intestinal microflora of a lower
      termite, Reticulitermes speratus, was examined by a strategy that does not rely
      on cultivation of the resident microorganisms. Small subunit ribosomal RNA
      (ssrRNA) genes were directly amplified from the mixed-population DNA of the
      termite gut by polymerase chain reaction (PCR) and clonally isolated. Most
      sequenced clones were phylogenetically affiliated with the four major groups of
      the domain Bacteria: the Proteobacteria group, the Spirochete group, the
      Bacteroides group, and the Low G + C gram-positive bacteria. The 16S rRNA
      sequence data show that the majority of the intestinal microflora of the termite
      consists of new species that are yet to be cultured. The phylogeny of a symbiotic
      methanogen inhabiting the gut of a lower termite (R. speratus) was analyzed
      without cultivation. The nucleotide sequence of the ssrDNA and the predicted
      amino acid sequence of the mcrA product were compared with those of the known
      methanogens. Both comparisons indicated that the termite symbiotic methanogen
      belonged to the order Methanobacteriales but was distinct from the known members
      of this order. The diversity of nitrogen-fixing organisms was also investigated
      without culturing the resident microorganisms. Fragments of the nifH gene, which
      encodes the dinitrogenase reductase, were directly amplified from the mixed
      population DNA of the termite gut and were clonally isolated. The phylogenetic
      analysis of the nifH amino acid sequences showed that there was a remarkable
      diversity of nitrogenase genes in the termite gut. The molecular phylogeny of a
      symbiotic hypermastigote Trichonympha agilis (class Parabasalia; order
      Hypermastigida) in the hindgut of R. speratus was also examined by the same
      strategy. The whole-cell hybridization experiments indicated that the sequence
      originated from a large hypermastigote in the termite hindgut, Trichonympha
      agilis. According to the phylogenetic trees constructed, the hypermastigote
      represented one of the deepest branches of eukaryotes. The hypermastigote along
      with members of the order Trichomonadida formed a monophyletic lineage,
      indicating that the hypermastigote and trichomonads shared a recent common
      ancestry.

PMID- 9783161
TI  - The essence of being extremophilic: the role of the unique archaeal membrane
      lipids.
AB  - In extreme environments, mainly Archaea are encountered. The archaeal cytoplasmic
      membrane contains unique ether lipids that cannot easily be degraded, are
      temperature- and mechanically resistant, and highly salt tolerant. Moreover,
      thermophilic and extreme acidophilic Archaea possess membrane-spanning tetraether
      lipids that form a rigid monolayer membrane which is nearly impermeable to ions
      and protons. These properties make the archaeal lipid membranes more suitable for
      life and survival in extreme environments than the ester-type bilayer lipids of
      Bacteria or Eukarya.

PMID- 9783162
TI  - Domain organization and biochemical features of Sulfolobus solfataricus DNA
      polymerase.
AB  - DNA polymerase from Sulfolobus solfataricus, strain MT4 (Sso DNA pol), was one of
      the first archaeal DNA polymerases to be isolated and characterized. Its encoding
      gene was cloned and sequenced, indicating that Sso DNA pol belongs to family B of
      DNA polymerases. By limited proteolysis experiments carried out on the
      recombinant homogeneous protein, we were able to demonstrate that the enzyme has
      a modular organization of its associated catalytic functions (DNA polymerase and
      3'-5' exonuclease). Indeed, the synthetic function was ascribed to the enzyme C
      terminal portion, whereas the N-terminal half was found to be responsible for the
      exonucleolytic activity. In addition, partial proteolysis studies were utilized
      to map conformational changes on DNA binding by comparing the cleavage map in the
      absence or presence of nucleic acid ligands. This analysis allowed us to identify
      two segments of the Sso DNA pol amino acid chain affected by structural
      modifications following nucleic acid binding: region 1 and region 2, in the
      middle and at the C-terminal end of the protein chain, respectively. Site
      directed mutagenesis studies will be performed to better investigate the role of
      these two protein segments in DNA substrate interaction.

PMID- 9783163
TI  - Thermozymes: biotechnology and structure-function relationships.
AB  - Recent findings on the biochemical and molecular features of the following
      thermozymes are presented, based on their biotechnological use: alpha-amylase and
      amylopullulanase, used in starch processing; glucose isomerase, used in sweetener
      production; alcohol dehydrogenase, used in chemical synthesis; and alkaline
      phosphatase, used in diagnostics. The corresponding genes and recombinant
      proteins have been characterized in terms of sequence similarities, specific
      activities, thermophilicity, and unfolding kinetics. Site-directed and nested
      deletion mutagenesis were used to understand structure-function relationships.
      All these thermozymes display higher stability and activity than their
      counterparts currently used in the biotechnology industry.

PMID- 9783164
TI  - Alkaline detergent enzymes from alkaliphiles: enzymatic properties, genetics, and
      structures.
AB  - The cleaning power of detergents seems to have peaked; all detergents contain
      similar ingredients and are based on similar detergency mechanisms. To improve
      detergency, modern types of heavy-duty powder detergents and automatic dishwasher
      detergents usually contain one or more enzymes, such as protease, amylase,
      cellulase, and lipase. Alkaliphilic Bacillus strains are often good sources of
      alkaline extracellular enzymes, the properties of which fulfil the essential
      requirements for enzymes to be used in detergents. We have isolated numbers of
      alkaliphilic Bacillus that produce such alkaline detergent enzymes, including
      cellulase (CMCase), protease, alpha-amylase, and debranching enzymes, and have
      succeeded in large-scale industrial production of some of these enzymes. Here, we
      describe the enzymatic properties, genetics, and structures of the detergent
      enzymes that we have developed.

PMID- 9783165
TI  - Microbial diversity of soda lakes.
AB  - Soda lakes are highly alkaline extreme environments that form in closed drainage
      basins exposed to high evaporation rates. Because of the scarcity of Mg2+ and
      Ca2+ in the water chemistry, the lakes become enriched in CO3(2-) and Cl-, with
      pHs in the range 8 to > 12. Although there is a clear difference in prokaryotic
      communities between the hypersaline lakes where NaCl concentrations are > 15% w/v
      and more dilute waters, i.e., NaCl concentrations about 5% w/v, photosynthetic
      primary production appears to be the basis of all nutrient recycling. In both the
      aerobic and anaerobic microbial communities the major trophic groups responsible
      for cycling of carbon and sulfur have in general been identified. Systematic
      studies have shown that the microbes are alkaliphilic and many represent separate
      lineages within accepted taxa, while others show no strong relationship to known
      prokaryotes. Although alkaliphiles are widespread it seems probable that these
      organisms, especially those unique to the hypersaline lakes, evolved separately
      within an alkaline environment. Although present-day soda lakes are geologically
      quite recent, they have probably existed since archaean times, permitting the
      evolution of independent communities of alkaliphiles since an early period in the
      Earth's history.

PMID- 9783166
TI  - Sugar utilization and its control in hyperthermophiles.
AB  - Many hyperthermophilic microorganisms show heterotrophic growth on a variety of
      carbohydrates. There has been considerable fundamental and applied interest in
      the utilization of glucose and its alpha- and beta-polymers by hyperthermophiles.
      While glycolysis by Bacteria at high temperatures shows conventional
      characteristics, it has been found that glucose catabolism by hyperthermophilic
      Archaea differs from the canonical glycolytic pathways, involves novel enzymes,
      and shows a unique control. This review addresses these aspects with specific
      attention to Pyrococcus furiosus, which is one of the best studied
      hyperthermophilic Archaea, has the capacity to grow on a variety of sugars
      including the marine beta-(1,3)-linked glucose polymer laminarin, and has been
      found to contain three novel glycolytic enzymes, two ADP-dependent kinases, and a
      ferredoxin-dependent glyceraldehyde-3-phosphate oxidoreductase.

PMID- 9783167
TI  - Biochemistry and biotechnology of mesophilic and thermophilic nitrile
      metabolizing enzymes.
AB  - Mesophilic nitrile-degrading enzymes are widely dispersed in the Bacteria and
      lower orders of the eukaryotic kingdom. Two distinct enzyme systems, a nitrilase
      catalyzing the direct conversion of nitriles to carboxylic acids and separate but
      cotranscribed nitrile hydratase and amidase activities, are now well known.
      Nitrile hydratases are metalloenzymes, incorporating FeIII or CoII ions in
      thiolate ligand networks where they function as Lewis acids. In comparison,
      nitrilases are thiol-enzymes and the two enzyme groups have little or no apparent
      sequence or structural homology. The hydratases typically exist as alpha beta
      dimers or tetramers in which the alpha- and beta-subunits are similar in size but
      otherwise unrelated. Nitrilases however, are usually found as homomultimers with
      as many as 16 subunits. Until recently, the two nitrile-degrading enzyme classes
      were clearly separated by functional differences, the nitrile hydratases being
      aliphatic substrate specific and lacking stereoselectivity, whereas the
      nitrilases are enantioselective and aromatic substrate specific. The recent
      discovery of novel enzymes in both classes (including thermophilic
      representatives) has blurred these functional distinctions. Purified mesophilic
      nitrile-degrading enzymes are typically thermolabile in buffered solution, rarely
      withstanding exposure to temperatures above 50 degrees C without rapid
      inactivation. However, operational thermostability is often increased by addition
      of aliphatic acids or by use of immobilized whole cells. Low molecular stability
      has frequently been cited as a reason for the limited industrial application of
      "nitrilases"; such statements notwithstanding, these enzymes have been
      successfully applied for more than a decade to the kiloton production of
      acrylamide and more recently to the smaller-scale production of nicotinic acid, R
      (-)-mandelic acid and S-(+)-ibuprofen. There is also a rapidly growing catalog of
      other potentially useful conversions of complex nitriles in which the
      regioselectivity of the enzyme coupled with the ability to achieve high
      conversion efficiencies without detriment to other sensitive functionalities is a
      distinct process advantage.

PMID- 9783168
TI  - pH homeostasis and ATP synthesis: studies of two processes that necessitate
      inward proton translocation in extremely alkaliphilic Bacillus species.
AB  - Alkaliphilic Bacillus species that are isolated from nonmarine, moderate salt,
      and moderate temperature environments offer the opportunity to explore strategies
      that have developed for solving the energetic challenges of aerobic growth at pH
      values between 10 and 11. Such bacteria share many structural, metabolic,
      genomic, and regulatory features with nonextremophilic species such as Bacillus
      subtilis. Comparative studies can therefore illuminate the specific features of
      gene organization and special features of gene products that are homologs of
      those found in non-extremophiles, and potentially identify novel gene products of
      importance in alkaliphily. We have focused our studies on the facultative
      alkaliphile Bacillus firmus OF4, which is routinely grown on malate-containing
      medium at either pH 7.5 or 10.5. Current work is directed toward clarification of
      the characteristics and energetics of membrane-associated proteins that must
      catalyze inward proton movements. One group of such proteins are the Na+/H+
      antiporters that enable cells to adapt to a sudden upward shift in pH and to
      maintain a cytoplasmic pH that is 2-2.3 units below the external pH in the most
      alkaline range of pH for growth. Another is the proton-translocating ATP synthase
      that catalyzes robust production of ATP under conditions in which the external
      proton concentration and the bulk chemiosmotic driving force are low. Three gene
      loci that are candidates for Na+/H+ antiporter encoding genes with roles in Na(+)
      dependent pH homeostasis have been identified. All of them have homologs in B.
      subtilis, in which pH homeostasis can be carried out with either K+ or Na+. The
      physiological importance of one of the B. firmus OF4 loci, nhaC, has been studied
      by targeted gene disruption, and the same approach is being extended to the
      others. The atp genes that encode the alkaliphile's F1F0-ATP synthase are found
      to have interesting motifs in areas of putative importance for proton
      translocation. As an initial step in studies that will probe the importance and
      possible roles of these motifs, the entire atp operon from B. firmus OF4 has been
      cloned and functionally expressed in an Escherichia coli mutant that has a full
      deletion of its atp genes. The transformant does not exhibit growth on succinate,
      but shows reproducible, modest increases in the aerobic growth yields on glucose
      as well as membrane ATPase activity that exhibits characteristics of the
      alkaliphile enzyme.

PMID- 9783169
TI  - Analysis of intracellular pH in the yeast Saccharomyces cerevisiae under elevated
      hydrostatic pressure: a study in baro- (piezo-) physiology.
AB  - Hydrostatic pressure is a distinctive feature of deep-sea environments, and this
      thermodynamic parameter has potentially inhibitory effects on organisms adapted
      to living at atmospheric pressure. In the yeast Saccharomyces cerevisiae,
      hydrostatic pressure causes a delay in or cessation of growth. The vacuole is a
      large acidic organelle involved in degradation of cellular proteins or storage of
      ions and various metabolites. Vacuolar pH, as determined using the pH-sensitive
      fluorescent dye 6-carboxyfluorescein, was analyzed in a hydrostatic chamber with
      transparent windows under elevated hydrostatic pressure conditions. A pressure of
      40-60 MPa transiently reduced the vacuolar pH by approximately 0.33. A vma3
      mutant defective in vacuolar acidification showed no reduction of vacuolar pH
      after application of hydrostatic pressure, indicating that the transient
      acidification is mediated through the function of vacuolar H(+)-ATPase. The
      vacuolar acidification was observed only in the presence of fermentable sugars,
      and never observed in the presence of ethanol, glycerol, or 3-o-methyl-glucose as
      the carbon source. Analysis of a glycolysis-defective mutant suggested that
      glycolysis or CO2 production is involved in the pressure-induced acidification.
      Hydration and ionization of CO2 is facilitated by elevated hydrostatic pressure
      because a negative volume change (delta V < 0) accompanies the chemical reaction.
      Moreover the glucose-induced cytoplasmic alkalization is inhibited by elevated
      hydrostatic pressure, probably because of inhibition of the plasma membrane H(+)
      ATPase. Therefore, the cytoplasm tends to become acidic under elevated
      hydrostatic pressure conditions, and this could be crucial for cell survival. To
      maintain a favorable cytoplasmic pH, the yeast vacuoles may serve as proton
      sequestrants under hydrostatic pressure. We are investigating the physiological
      effects of hydrostatic pressure in the course of research in a new experimental
      field, baro-(piezo-) physiology.

PMID- 9783170
TI  - Bacteria tolerant to organic solvents.
AB  - The toxic effects that organic solvents have on whole cells is an important
      drawback in the application of these solvents in environmental biotechnology and
      in the production of fine chemicals by whole-cell biotransformations. Hydrophobic
      organic solvents, such as toluene, are toxic for living organisms because they
      accumulate in and disrupt cell membranes. The toxicity of a compound correlates
      with the logarithm of its partition coefficient with octanol and water (log
      P(ow)). Substances with a log P(ow) value between 1 and 5 are, in general, toxic
      for whole cells. However, in recent years different bacterial strains have been
      isolated and characterized that can adapt to the presence of organic solvents.
      These strains grow in the presence of a second phase of solvents previously
      believed to be lethal. Different mechanisms contributing to the solvent tolerance
      of these strains have been found. Alterations in the composition of the
      cytoplasmic and outer membrane have been described. These adaptations suppress
      the effects of the solvents on the membrane stability or limit the rate of
      diffusion into the membrane. Furthermore, changes in the rate of the biosynthesis
      of the phospholipids were reported to accelerate repair processes. In addition to
      these adaptation mechanisms compensating the toxic effect of the organic
      solvents, mechanisms do exist that actively decrease the amount of the toxic
      solvent in the cells. An efflux system actively decreasing the amount of solvents
      in the cell has been described recently. We review here the current knowledge
      about exceptional strains that can grow in the presence of toxic solvents and the
      mechanisms responsible for their survival.

PMID- 9783171
TI  - Improvement of organic solvent tolerance level of Escherichia coli by
      overexpression of stress-responsive genes.
AB  - Water-immiscible organic solvents can be toxic to microorganisms. The tolerance
      levels differ among strains of Escherichia coli, suggesting that the organic
      solvent tolerance level is strain specific and determined genetically. We
      constructed several mutants from E. coli, of which the organic solvent tolerance
      levels were improved. The mutants were defective in the marR gene encoding a
      repressor protein for the mar operon that is responsible for environmental stress
      factors. High expression of stress-responsive genes, soxS, marA, and robA,
      elevated organic solvent tolerance levels of several strains of E. coli. These
      genes code for DNA-binding proteins that are transcriptional activators belonging
      to the AraC subfamily with the helix-turn-helix motif. It was shown that
      expression of the AcrAB-TolC system, a major efflux pump in E. coli, was
      positively regulated by the proteins. This system was highly expressed in the
      organic solvent-tolerant mutants. Strains defective in one of the genes, acrA,
      acrB, or tolC, were remarkably sensitive to organic solvents.

PMID- 9783172
TI  - Developments toward large-scale bacterial bioprocesses in the presence of bulk
      amounts of organic solvents.
AB  - Many pseudomonads and other bacteria can grow on aliphatic and aromatic
      hydrocarbons that occur in the environment. We are examining the potential of
      such organisms as biocatalysts for the oxidation of a variety of substituted
      aliphatic and aromatic compounds. To attain a high production rate of oxidation
      products via such biotransformations, we have focused on two-liquid phase culture
      systems. In these systems, cells are grown in liquid media consisting of an
      aqueous phase containing water-soluble growth substrates and droplets of a water
      immicible organic solvent containing bioconversion substrates and products. For
      industrial applications of such two-liquid phase processes, several questions
      remain. What are the maximum rates at which apolar compounds can be transferred
      from the apolar phase to cells growing in the aqueous phase, i.e., what are the
      maximum space-time yields attainable in two-liquid phase fermentations under
      practical conditions? What does an efficient downstream processing of two-liquid
      phase medium involve? What safety regimes should be considered in working with
      flammable organic solvents? Can elevated pressure be used to increase oxygen
      transfer? Based on answers to these questions, we have recently developed a high
      pressure, explosion-proof bioreactor system with Bioengineering AG (Wald,
      Switzerland), which will be installed in our pilot plant and used to explore two
      liquid phase bioconversions at a pilot scale.

PMID- 9783173
TI  - Anaerobic alkalithermophiles, a novel group of extremophiles.
AB  - Although some anaerobic and aerobic mesophiles have long been known to grow at
      alkaline pH (above 9.5), little was known until recently about thermophilic
      alkaliphiles, termed now alkalithermophiles. This minireview describes presently
      known and recently validly described anaerobic alkalithermophilic bacteria
      (pHopt55C > 8.5; Topt > 55 degrees C) and alkalitolerant thermophiles (pHopt55C <
      8.5 but pHmax55C above 9.0). Some of these are widely distributed, but others
      have been isolated (thus far) only from one specific location. This novel group
      of anaerobic bacteria is comprised of physiologically different genera and
      species which, so far, all belong to the Gram-type positive Bacillus-Clostridium
      phylogenetic subbranch. An interesting feature of these anaerobic
      alkalithermophiles is that most of the isolates have short doubling times. The
      fastest growing among them are strains of Thermobrachium celere, with doubling
      times as short as 10 min while growing above pH 9.0 and above 55 degrees C.

PMID- 9783174
TI  - Taxonomy and biotransformation activities of some deep-sea actinomycetes.
AB  - Deep-sea soft sediments from trench systems and depths in the northwestern
      Pacific Ocean ranging from less than 300 to 10,897 m in depth have been analyzed
      for three target genera of actinomycetes: Micromonospora, Rhodococcus, and
      Streptomyces. Only culturable strains, recovered at atmospheric pressure on
      selective isolation media, have been examined to date. Maximum recoveries of
      culturable bacteria were greater that 10(7)/ml wet g sediment, but actinomycetes
      comprised a small proportion of this population (usually less than 1%). The
      target actinomycetes were isolated at all depths except from the Mariana Trench
      sediments. Actinomycete colonies were defined initially on the basis of colony
      morphologies, and preliminary identification then was made by chemotaxonomic
      tests. Pyrolysis mass spectrometry (PyMS) of deep-sea mycolic acid-containing
      actinomycetes gave excellent correspondence with numerical (phenetic) taxonomic
      analyses and subsequently was adopted as a rapid procedure for assessing
      taxonomic diversity. PyMS analysis enabled several clusters of deep-sea
      rhodococci to be distinguished that are quite distinct from all type strains. 16S
      rRNA gene sequence analysis has revealed that several of these marine rhodococci
      have sequences that are very similar to certain terrestrial species of
      Rhodococcus and to Dietzia. There is evidence for the intrusion of terrestrial
      runoff into these deep trench systems, and the inconsistency of the phenotypic
      and molecular taxonomies may reflect recent speciatiion events in actinomycetes
      under the high-pressure conditions of the deep sea. The results of DNA-DNA
      pairing experiments point to the novelty of Rhodococcus strains recovered from
      hadal depths in the Izu Bonin Trench. Biotransformation studies of deep-sea
      bacteria have focused on nitrile compounds. Nitrile-metabolizing bacteria,
      closely related to rhodococci, have been isolated that grow well at low
      temperature, high salt concentrations, and high pressures, suggesting that they
      are of marine origin or have adapted to the deep-sea environment.

PMID- 9783175
TI  - Halobacteria: the evidence for longevity.
AB  - Subterranean salt deposits are the remains of ancient hypersaline waters that
      presumably supported dense populations of halophilic microorganisms including
      representatives of the haloarchaea (halobacteria). Ancient subterranean salt
      deposits (evaporites) are common throughout the world, and the majority sampled
      to date appear to support diverse populations of halobacteria. The
      inaccessibility of deep subsurface deposits, and the special requirements of
      these organisms for survival, make contamination by halobacteria from surface
      sites unlikely. It is conceivable that these subterranean halobacteria are
      autochthonous, presumably relict populations derived from ancient hypersaline
      seas that have been revived from a state of dormancy. One would predict that
      halobacteria that have been insulated and isolated inside ancient evaporites
      would be different from comparable bacteria from surface environments, and that
      it might be possible to use a molecular chronometer to establish if the
      evolutionary position of the subsurface isolates correlated with the geological
      age of the evaporite. Extensive comparisons have been made between the 16S rRNA
      genes of surface and subsurface halobacteria without showing any conclusive
      differences between the two groups. A further phylogenetic comparison exploits an
      unusual feature of one particular group of halobacteria that possess at least two
      heterogeneous copies of the 16S rRNA gene, the sequences of which may have been
      converging or diverging over geological time. However, results to date have yet
      to show any gene sequence differences between surface and evaporite-derived
      halobacteria that might arguably be an indication of long-term dormancy.

PMID- 9783176
TI  - Diversity of extremely halophilic bacteria.
AB  - In this review, the history of the classification of the family Halobacteriaceae,
      the extremely halophilic aerobic Archaea, is reviewed with some emphasis on the
      recently described new genera Halobaculum, Halorubrum, Natrialba, Natronomonas,
      and "Haloterrigena." Speculation is made about the evolutionary relationship
      between members of the Halobacteriaceae and the extremely halophilic, anaerobic
      methanogens of the genera Methanohalobium and Methanohalophilus. Efforts to find
      missing links between the two groups are also reviewed.

PMID- 9783177
TI  - Moderately halophilic gram-positive bacterial diversity in hypersaline
      environments.
AB  - Moderately halophilic bacteria are microorganisms that grow optimally in media
      containing 3%-15% (w/v) salt. They are represented by a heterogeneous group of
      microorganisms included in many different genera. Gram-negative moderately
      halophilic bacteria have been studied in more detail, but studies on gram
      positive species are more scarce. Recent studies carried out by our research
      group on gram-positive moderate halophiles have permitted clarifying their
      taxonomic and phylogenetic position and describing new species. Thus, we have
      isolated six strains from ponds of salterns that show phenotypic and genotypic
      characteristics similar to those of Nesterenkonia halobia (formerly Micrococcus
      halobius), a moderately halophilic gram-positive coccus that was described on the
      basis of a single strain. Our data demonstrate quite clearly that they are
      members of this species and contribute to a better description of these
      moderately halophilic cocci. Similarly, a study of a large number of gram
      positive moderately halophilic rods that were able to produce endospores led us
      to describe a new species, designated Bacillus salexigens. Further, isolates
      grouped in other three phenons, obtained by numerical taxonomy analysis and
      showing phenotypic features quite similar to those of this species, represent
      different genomovars, with very low DNA-DNA homology. Although they might
      represent additional new species, it will be necessary to determine new
      phenotypic features to differentiate them from previously described Bacillus
      species. We have also studied the viability of some old enrichments provided by
      B.E. Volcani, which were set up in 1936. We isolated 31 gram-positive motile
      endospore-forming rods that, according to their phenotypic characteristics, could
      represent a new species of the genus Bacillus.

PMID- 9783178
TI  - Completing the sequence of the Sulfolobus solfataricus P2 genome.
AB  - The Sulfolobus solfataricus P2 genome collaborators are poised to sequence the
      entire 3-Mbp genome of this crenarchaeote archaeon. About 80% of the genome has
      been sequenced to date, with the rest of the sequence being assembled fast. In
      this publication we introduce the genomic sequencing and automated analysis
      strategy and present intial data derived from the sequence analysis. After an
      overview of the general sequence features, metabolic pathway studies are
      explained, using sugar metabolism as an example. The paper closes with an
      overview of repetitive elements in S. solfataricus.

PMID- 9783179
TI  - Life on Mars: chemical arguments and clues from Martian meteorites.
AB  - Primitive terrestrial life-defined as a chemical system able to transfer its
      molecular information via self-replication and to evolve-probably originated from
      the evolution of reduced organic molecules in liquid water. Several sources have
      been proposed for the prebiotic organic molecules: terrestrial primitive
      atmosphere (methane or carbon dioxide), deep-sea hydrothermal systems, and
      extraterrestrial meteoritic and cometary dust grains. The study of carbonaceous
      chondrites, which contain up to 5% by weight of organic matter, has allowed close
      examination of the delivery of extraterrestrial organic material. Eight
      proteinaceous amino acids have been identified in the Murchison meteorite among
      more than 70 amino acids. Engel reported that L-alanine was surprisingly more
      abundant than D-alanine in the Murchison meteorite. Cronin also found excesses of
      L-enantiomers for nonprotein amino acids. A large collection of micrometeorites
      has been recently extracted from Antarctic old blue ice. In the 50- to 100-micron
      size range, carbonaceous micrometeorites represent 80% of the samples and contain
      2% of carbon, on average. They might have brought more carbon than that involved
      in the present surficial biomass. The early histories of Mars and Earth clearly
      show similarities. Liquid water was once stable on the surface of Mars, attesting
      the presence of an atmosphere capable of deccelerating C-rich micrometeorites.
      Therefore, primitive life may have developed on Mars as well and fossilized
      microorganisms may still be present in the near subsurface. The Viking missions
      to Mars in 1976 did not find evidence of either contemporary or past life, but
      the mass spectrometer on the lander aeroshell determined the atmospheric
      composition, which has allowed a family of meteorites to be identified as
      Martian. Although these samples are essentially volcanic in origin, it has been
      recognized that some of them contain carbonate inclusions and even veins that
      have a carbon isotopic composition indicative of an origin from Martian
      atmospheric carbon dioxide. The oxygen isotopic composition of these carbonate
      deposits allows calculation of the temperature regime existing during formation
      from a fluid that dissolved the carbon dioxide. As the composition of the fluid
      is unknown, only a temperature range can be estimated, but this falls between 0
      degree and 90 degrees C, which would seem entirely appropriate for life
      processes. It was such carbonate veins that were found to host putative
      microfossils. Irrespective of the existence of features that could be considered
      to be fossils, carbonate-rich portions of Martian meteorites tend to have
      material, at more than 1000 ppm, that combusts at a low temperature; i.e., it is
      an organic form of carbon. Unfortunately, this organic matter does not have a
      diagnostic isotopic signature so it cannot be unambiguously said to be indigenous
      to the samples. However, many circumstantial arguments can be made to the effect
      that it is cogenetic with the carbonate and hence Martian. If it could be proved
      that the organic matter was preterrestrial, then the isotopic fractionation
      between it and the carbon is in the right sense for a biological origin.

PMID- 9783180
TI  - Distribution and diversity of halophilic bacteria in a subsurface salt formation.
AB  - The Waste Isolation Pilot Plant (WIPP) is a salt mine constructed 650 meters
      below the ground surface by the United States Department of Energy. The facility
      will be used for permanent disposal of transuranic wastes. This underground
      repository has been constructed in the geologically stable Permian age Salado
      salt formation. Of the wastes to be placed into the facility, 85% will be
      biodegradable cellulose. A 3-year survey of the bacterial populations existing
      within the facility was conducted. Bacterial populations were found to be
      heterogeneously distributed throughout the mine. Populations in some mine areas
      reached as high as 1.0 x 10(4) colony-forming units per gram of NaCl. The
      heterogeneous distribution of bacteria within the mine did not follow any
      recognizable pattern related to either age of the workings or to human activity.
      A biochemical comparison between ten known species of halophilic bacteria, and
      strains isolated from both the mine and nearby surface hypersaline lakes, showed
      the presence of extreme halophiles with wide biochemical diversity, some of which
      could prove to represent previously undescribed groups. The halophilic bacteria
      isolated from the mine were found to degrade cellulose and a wide variety of
      other carbon compounds. When exposed to two types of common laboratory paper, the
      cellulose-degrading halophiles attached to the substrate within 30 minutes of
      inoculation. Cultures enriched directly from a brine seep in the mine easily
      destroyed both papers and produced detectable amounts of oxalacetic and pyruvic
      acids. The combination of heterogeneity in the distribution of organisms, the
      presence of a physiologically diverse community, and the relatively slow
      metabolism of cellulose may explain several long-standing debates about the
      existence of microorganisms in ancient underground salt formations.

PMID- 9783181
TI  - Nucleoside diphosphate kinase from haloalkaliphilic archaeon Natronobacterium
      magadii: purification and characterization.
AB  - An ATP-binding protein from the haloalkaliphilic archaeon Natronobacterium
      magadii was purified and characterized by affinity chromatography on ATP-agarose
      and by fast protein liquid chromatography (FPLC) on a Mono Q column. The N
      terminal 20 amino acid sequence of the kinase showed a strong sequence similarity
      of this protein with nucleoside diphosphate (NDP) kinases from different
      organisms and, accordingly, we believe that this protein is a nucleoside
      diphosphate kinase, an enzyme whose main function is to exchange gamma-phosphates
      between nucleoside triphosphates and diphosphates. Comparison of the molecular
      weights of the NDP kinase monomer determined by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) (23,000) and of the oligomer
      determined by sedimentation equilibrium experiments (125,000) indicated that the
      oligomer is a hexamer. The enzyme was autophosphorylated in the presence of
      [gamma-32P]ATP, and Mg2+ was required for the incorporation of phosphate. The
      kinase preserved the ability to transfer gamma-phosphate from ATP to GDP in the
      range of NaCl concentration from 90 mM to 3.5 M and in the range of pH from 5 to
      12. It was found and confirmed by Western blotting that this kinase is one of the
      proteins that bind specifically to natronobacterial flagellins. NDP kinase from
      haloalkaliphiles appeared to be simple to purify and to be a suitable enzyme for
      studies of structure and stability compared with NDP kinases from mesophilic
      organisms.

PMID- 9783182
TI  - Pressure enhances thermal stability of DNA polymerase from three thermophilic
      organisms.
AB  - DNA polymerases derived from three thermophilic microorganisms, Pyrococcus strain
      ES4, Pyrococcus furiosus, and Thermus aquaticus, were stabilized in vitro by
      hydrostatic pressure at denaturing temperatures of 111 degrees C, 107.5 degrees
      C, and 100 degrees C (respectively). Inactivation rates, as determined by enzyme
      activity measurements, were measured at 3, 45, and 89 MPa. Half-lives of P.
      strain ES4, P. furiosus, and T. aquaticus DNA polymerases increased from 5.0,
      6.9, and 5.2 minutes (respectively) at 3 MPa to 12, 36, and 13 minutes
      (respectively) at 45 MPa. A pressure of 89 MPa further increased the half-lives
      of P. strain ES4 and T. aquaticus DNA polymerases to 26 and 39 minutes, while the
      half-life of P. furiosus DNA polymerase did not increase significantly from that
      at 45 MPa. The decay constant for P. strain ES4 and T. aquaticus polymerases
      decreased exponentially with increasing pressure, reflecting an observed change
      in volume for enzyme inactivation of 61 and 73 cm3/mol, respectively.
      Stabilization by pressure may result from pressure effects on thermal unfolding
      or pressure retardation of unimolecular inactivation of the unfolded state.
      Regardless of the mechanism, pressure stabilization of proteins could explain the
      previously observed extension of the maximum temperature for survival of P.
      strain ES4 and increase the survival of thermophiles in thermally variable deep
      sea environments such as hydrothermal vents.

PMID- 9783183
TI  - A novel thermostable nitrile hydratase.

PMID- 9783184
TI  - Dietzia natronolimnaios sp. nov., a new member of the genus Dietzia isolated from
      an east African soda lake.
AB  - Two novel alkaliphilic aerobic organotrophic bacteria have been isolated from a
      moderately saline and alkaline East African soda lake. The new isolates grow at
      pH values between 6 and 10, with a pH optimum for growth of 9.0, and at a salt
      concentration between 0% and 10% (w/v). Phylogenetic analysis based on 16S rDNA
      sequence shows that these isolates are very closely related (99.6% similarity)
      and are members of the monospecific genus Dietzia (98.8% and 98.7% similarity).
      DNA/DNA hybridization revealed a relatedness of 83% between the two isolates, but
      only 8% between them and the type strain Dietzia maris. The G + C content as
      measured by thermal denaturation is 66.1 mol%. Phenotypic comparisons between D.
      maris and one isolate showed that they share very similar morphological and
      chemotaxonomic properties, but differ significantly in carbon source utilization
      profiles and halotolerance in alkaline medium. We propose a second species of
      this genus which we name Dietzia natronolimnaios (type strain 15LN1 = CBS
      107.95).

PMID- 9783185
TI  - Extremophile microorganisms as cell factories: support from the European Union.

PMID- 9783186
TI  - Was the environment for primordial life hypersaline?

PMID- 9783187
TI  - [50th Annual Meeting of the American Academy of Neurology (AAN). Minneapolis, 25
      April--2 May 1998. 151st Annual Meeting of the American Psychiatric Association
      (APA). Toronto, 31 May--3 June 1998].

PMID- 9783188
TI  - [Long-term clinical outcome of extracorporeal shock wave lithotripsy monotherapy
      for staghorn calculi].
AB  - We treated 97 patients with staghorn calculi by ESWL monotherapy using a
      Lithostar Lithotriptor (Siemens) between January 1989 and December 1996.
      Seventeen patients (18 renal units) out of 45 patients (47 renal units) who could
      be followed up for more than 12 months after ESWL had no stones on radiographs at
      3 months after the treatment. The actuarial non-recurrence (or stone-free) rate
      was 88.9% at 1 year, 79.0% at 3 years, and 63.2% at 5 years after ESWL (Kaplan
      Meier method). The actuarial non-regrowth rate (regrowth < 1 mm) was 96.6% at 1
      year, 72.8% at 3 years, and 63.7% at 5 years (Kaplan-Meier method). History of
      urinary stones was a significant risk factor for stone recurrence, while patient
      sex, affected side, stone number, pyuria (> or = 10/HPF), hydronephrosis on DIP,
      and staghorn type were not significantly associated with stone recurrence or
      regrowth (Cox proportional hazard model). Late complications associated with ESWL
      included renal dysfunction (serum Cr > or = 1.1 mg/dl) in 2 patients,
      hypertension (> or = 160 mmHg) in 3, and renal atrophy (two-dimensional size < or
      = 80%) in 5. ESWL exerted adverse effects in a session-dependent manner on the
      kidney resulting in renal atrophy. Therefore, we highly recommend that ESWL
      should be limited to less than 10 sessions.

PMID- 9783189
TI  - [Short-term intravesical instillation of pirarubicin (THP) in prophylactic
      treatment after transurethral resection of superficial bladder tumor].
AB  - We conducted a prospective randomized controlled study on the prophylactic
      effects of short-term intravesical instillation of pirarubicin (THP) against
      recurrence to determine the effective administration schedule. All patients gave
      their informed consent. The subjects included bladder cancer patients who had pTa
      or pT1, and G1 or G2 cancer, and became tumor-free after transurethral resection
      of the bladder tumor (TUR-BT). After dissolving 30 mg of THP into 5 ml of
      distilled water, physiological saline was added to adjust the total volume to 50
      ml, which was then instilled into the bladder, and was retained for 5 minutes.
      The schedule of instillation was for daily for 7 consecutive days from the day of
      TUR-BT and subsequently once a week for 10 weeks, 17 times in total for Group I,
      and once every two weeks for 6 months (12 times) starting 2 weeks after TUR and
      subsequently once a month until one year had passed after surgery (6 times), 18
      times in total for Group II. The total number of cases was 69 (36 in Group I, 33
      in Group II). The tumor-free ratios determined by the Kaplan-Meier analysis were
      93.9% in Group I and 72.7% in Group II for one year, and 86.8% in Group I and
      59.5% in Group II for two years. There was a statistically significant difference
      in the tumor-free ratios between the two groups by the generalized Wilcoxon test
      and the Log rank test (p = 0.0145 and 0.0107, respectively). Multivariated
      analysis using Cox's comparison hazard model produced p-values of 0.0002, 0.0007,
      0.0009 and 0.0040 in the order of therapeutic mode, initial onset/recurrence,
      stage and number of tumor. Adverse events that forced discontinuation of the
      therapy for a while occurred in 4.3%. These results demonstrated that short-term
      intensive intravesical instillation of THP immediately after TUR-BT was a safe
      and effective therapy.

PMID- 9783190
TI  - [Evaluation of transition zone biopsy in systematic prostate biopsy].
AB  - We evaluated the systematic biopsies performed on 83 patients suspected of having
      prostate cancer. In the systematic biopsy, 6 cores were from the peripheral zone
      and 2 cores from the transition zone. Cancer was detected in 25 patients (30.1%).
      The percentage of patients who had abnormal digital rectal examination and
      transrectal echo findings, average PSA and PSA density, and the number of
      examinations which suggested cancer were higher in the cancer group than in the
      non-cancer group, although the mean prostate volume was smaller. Cancer was more
      frequently detected in the peripheral zone than in the transition zone. Cancer
      was detected only in the transition zone in only 1 of the 25 cancer patients. We
      conclude that biopsy of the transition zone to all the patients is not always
      needed in systematic biopsy.

PMID- 9783191
TI  - [Pretreatment with chlormadinone acetate in prostate cancer patients treated with
      a luteinizing hormone-releasing hormone analogue].
AB  - We evaluated the efficacy of pretreatment with chlormadinone acetate (CMA) in
      preventing the initial testosterone surge induced by luteinizing hormone
      releasing hormone (LH-RH) analogue. A total of 44 patients with previously
      untreated prostate cancer was included in this study. Patients were randomly
      assigned to 2 treatment groups: Group I-CMA therapy was begun 4 weeks before the
      initial LH-RH analogue injection. Group II-CMA therapy was begun 2 weeks before
      the initial LH-RH analogue injection. After the initial LH-RH analogue injection,
      CMA was administered for 12 weeks or more. After LH-RH analogue application mean
      values of serum luteinizing hormone (LH) and testosterone increased in both
      groups on day 3. However, LH and testosterone levels remained below pretreatment
      values in both groups. CMA pretreatment reduced the mean serum PSA. The mean
      relative PSA level slightly increased after administration of the LH-RH analogue
      in group I on day 7. In group II, the mean relative PSA level decreased after LH
      RH analogue administration. Objective response rates at 12 weeks were 83.3% and
      93.8% in group I and group II. Our results indicate that pretreatment with CMA
      for 2 weeks appeared to be sufficient to prevent the initial testosterone surge
      induced by LH-RH analogue.

PMID- 9783192
TI  - [Clinical efficacy and reduction effect on prostatic volume of chlormadinone
      acetate combined with tamsulosin hydrochloride in benign prostatic hyperplasia
      patients insufficiently treated with tamsulosin hydrochloride only].
AB  - Alpha adrenergic blocker has become the first choice in the medical treatment of
      benign prostatic hyperplasia (BPH). The efficacy of alpha adrenergic blocker has
      been suggested to be related to the prostatic tissue components, and to be
      ineffective in treating the clinical symptoms caused by BPH in some cases. The
      efficacy and prostate reduction of an anti-androgenic agent, chlormadinone
      acetate, combined with alpha adrenergic blocker, tamsulosin hydrochloride, were
      evaluated using 40-BPH patients insufficiently treated with tamsulosin
      hydrochloride alone. Fifty mg of chlormadinone acetate and 0.2 mg of tamsulosin
      hydrochloride were administered orally once a day for 16 weeks to patients with a
      prostate subjective symptoms score, I-PSS, of greater than 13 or a peak flow rate
      of less than 12 ml/s, even after the treatment with 0.2 mg of tamsulosin
      hydrochloride alone for more than four weeks. Total I-PSS decreased significantly
      after four weeks. The total irritative symptom score did not change for 16 weeks,
      but the total obstructive symptom score decreased significantly, as did the total
      I-PSS. In objective data, the estimated volume of both total prostate and the
      transition zone on transrectal ultrasonogram decreased significantly at the end
      of the treatment, and the peak flow rate decreased significantly after 12 weeks.
      These findings suggest that the addition of chlormadinone acetate may be a
      reasonable alternative in the treatment of BPH patients responding insufficiently
      to tamsulosin hydrochloride alone, and that combination therapy using
      chlormadinone acetate and tamsulosin hydrochloride may be useful for BPH patients
      with serious obstructive symptoms.

PMID- 9783194
TI  - [Surgical removal of adrenal hemangioma after five years of follow-up: a case
      report].
AB  - A case of adrenal hemangioma is reported. A 2.5 x 2.5 cm right adrenal tumor was
      discovered incidentally in a 61-year-old woman by computed tomography in October
      1992. Hormonal levels were within the normal ranges, and the patient was followed
      for five years under a diagnosis of non-functioning adrenal tumor. The tumor
      enlarged slowly to 4.6 x 4.2 cm. Then the tumor was removed surgically and the
      pathological examination revealed adrenal cavernous hemangioma.

PMID- 9783193
TI  - [Composite pheochromocytoma with ganglioneuroma in the adrenal gland: a case
      report].
AB  - A 67-year-old male demonstrated a right adrenal tumor at another hospital, and
      consulted our hospital for surgical treatment. Abdominal computed tomography
      revealed a 13 x 12 cm mass in the right adrenal region. Serum and urinary
      adrenaline levels were high, and the catecholamine levels in the blood sample of
      the selective adrenal vein were also high. The tumor was 1,325 g in weight and 13
      x 9 x 18 cm in diameter. Pathological diagnosis was a mixed neuroendocrine-neural
      tumor. It was composed of pheochromocytoma and ganglioneuroma. This combination
      in the adrenal gland is rare. We reviewed 3 previously reported cases of
      composite pheochromocytoma with gangloineuroma in the adrenal gland in the
      Japanese literature, and this is considered to be the fourth case.

PMID- 9783195
TI  - [A case of asynchronous renal cell carcinoma, hepatocellular carcinoma and
      residual ureteral cancer].
AB  - A case of asynchronous triple cancer in an 88-year-old male is reported. Six
      years ago, he had received left radical nephrectomy for renal cell carcinoma, and
      2 years ago partial hepatectomy for hepatocellular carcinoma detected by follow
      up computed tomography (CT). During the post-operative follow-up, no metastasis
      of either the renal or hepatic carcinoma was detected. On February 12, 1997 he
      presented with macroscopic hematuria. Cystoscopy revealed a tumor emerging from
      the left ureteral orifice, while CT and magnetic resonance imaging (MRI) revealed
      a tumor mass in the left exterior of bladder. Diagnosis of residual ureter tumor,
      we performed both left ureterectomy and partial cystectomy. Histological
      diagnosis revealed transitional cell carcinoma of the residual ureter (G2 > G3,
      pT1, pV0, pL0, pR0). Convalescence was uneventful and 10 months after the
      operation, he is alive with no recurrence or metastasis. We stress the importance
      of careful follow-up not only to perceive the recurrence or metastasis of renal
      cancer but also to detect cancer in other parts of the body.

PMID- 9783196
TI  - [Bellini duct carcinoma of the kidney: a case report].
AB  - A case of Bellini duct carcinoma is reported. A 71-year-old woman visited our
      hospital with a chief complaint of lower abdominal pain. Computerized tomography,
      ultrasonography showed a mass lesion measuring about 5 cm in the right kidney.
      Angiography showed an avascular mass lesion in the right kidney. Right radical
      nephrectomy was performed under the diagnosis of renal cell carcinoma.
      Histological examinations showed Bellini duct carcinoma of the papillary type. We
      performed M-VAC (methotrexate, vinblastine, doxorubicin, icisplatin) therapy as
      is used for transitional cell carcinoma. She is alive with no evidence of disease
      5 months after her surgical treatment. To our knowledge, only 32 cases of Bellini
      duct carcinoma have been reported in the Japanese literature.

PMID- 9783197
TI  - [Metastatic renal tumor originating from esophageal carcinoma: a case report].
AB  - We report a case of renal metastasis from esophageal carcinoma. The patient was a
      74-year-old man, who had undergone an operation for esophageal carcinoma thirteen
      months previously. He was admitted to our clinic for examination of a right renal
      mass. Computed tomography (CT) revealed an irregular low density area in the
      right kidney and angiography showed a hypovascular tumor. Partial nephrectomy was
      performed. Histological examination revealed squamous cell carcinoma and the
      diagnosis was metastasis of esophageal carcinoma. Metastatic renal tumors are
      rarely encountered clinically and, to our knowledge, the present case is only the
      16th clinical report of the renal metastasis of esophageal carcinoma in Japan.
      However, metastasis to the kidney is relatively common at autopsy. It is the
      fifth most common site of metastasis following the lungs, liver, bones and
      adrenals. Consequently, patients with malignancy should be followed up while
      keeping renal metastasis in mind.

PMID- 9783198
TI  - [Endopyelotomy with Acucise for secondary ureteropelvic junction obstruction:
      report of a case].
AB  - We report a case of successful endopyelotomy using the Acucise cutting balloon
      device for secondary ureteropelvic junction obstruction (UPJO). A 23-year-old man
      was hospitalized with the chief complaint of left lumbago and left hydronephrosis
      due to left UPJO. He underwent antegrade endopyelotomy with a nephroscope and
      open pyeloplasty. However, left lumbago and hydronephrosis did not show
      improvement. Acucise endopyelotomy was performed under epidural anesthesia. The
      operative time was 55 minutes and the hospital stay after the operation was 4
      days. There were no operative complications and 3 months later, the operative
      results were satisfactory as determined by drip infusion pyelography and the
      disappearance of the lumbago.

PMID- 9783200
TI  - [Gastrocystoplasty for severely contracted bladder following high dose pelvic
      irradiation: a case report].
AB  - A 24-year-old female who had received hysterectomy and adnexectomy of bilateral
      appendages for yolk sac tumor at the age of 12 years, followed by repeated
      surgery and pelvic irradiation over a total of 100 Gy for relapse of tumor,
      suffered from a severely contracted bladder and renal dysfunction of serum
      creatinine level over 2.0 mg/dl. The diagnosis was radiation-induced contracted
      bladder with renal dysfunction due to vesicoureteral reflux. Since the small
      intestine was not considered suitable after high dose irradiation, the stomach
      was used to reconstruct the bladder. The vesical pressure, which was 70 cmH2O at
      the capacity of 30 ml, was decreased to 22 cmH2O at the capacity of 100 ml, 5
      weeks after surgery. The renal function was stable with a serum creatinine level
      below 1.4 mg/dl and the bladder capacity was 200 ml, 15 months after surgery.
      This method using the stomach was considered valuable for bladder reconstruction
      after large dose pelvic irradiation.

PMID- 9783199
TI  - [A case of primary malignant lymphoma of the bladder].
AB  - The patient was a 34-year-old male. He visited a community hospital complaining
      of macroscopic hematuria and pollakiuria. Cystoscopic examination demonstrated a
      bladder tumor. Transurethral resection of the bladder tumor (TUR-Bt) was
      performed. Histological examination disclosed malignant lymphoma (non-Hodgkin's
      lymphoma, mixed type). The tumor was classified into the B cell type by the
      immunohistological staining with surface antigens. He was referred to St.
      Marianna University, School of Medicine for chemotherapy. Pelvic computed
      tomography (CT) after admission demonstrated a tumor with a wide pedicle located
      in the vesicle triangle extending to the posterolateral wall of the bladder. No
      abnormalities were found in other organs. After establishment of the diagnosis of
      primary bladder malignant lymphoma, 6 courses of chemotherapy (adriamycin,
      vincristine, cyclophosphamide, prednisolone, etoposide, methotrexate) were
      performed. The tumor disappeared completely on imaging studies after
      chemotherapy. Biopsy of the bladder disclosed no abnormal tissues. No evidence of
      recurrence or metastasis was found 5 years after chemotherapy.

PMID- 9783201
TI  - [Small cell carcinoma of the prostate: a case report].
AB  - A 57-year-old man was admitted with the chief complaint of macrohematuria.
      Digital rectal examination showed a slightly enlarged, irregular prostate with
      stony consistency. Serum levels of prostate specific antigen (PSA), neuron
      specific enolase (NSE) and progastrin-releasing peptide (ProGRP) were elevated.
      Transurethral resection (TUR)-biopsy of the prostate revealed small cell
      carcinoma with poorly differentiated adenocarcinoma. Various radiological
      examinations revealed metastases to pelvic lymph nodes and liver. He was treated
      with chemoendocrine therapy consisting of cisplatin, etoposide, flutamide and
      luleinizing hormone-releasing hormone (LH-RH) agonist. The primary tumor and
      metastatic lesion decreased and serum PSA, NSE and ProGRP levels were decreased
      to normal ranges after 5 cycles of chemotherapy. After the 5-cycle chemotherapy,
      TUR-biopsy proved viable tumor cells. During the additional chemotherapy, tumor
      markers increased and 4 months later liver metastasis progressed. He died 13
      months after diagnosis of small cell carcinoma of the prostate.

PMID- 9783202
TI  - [Rhabdomyosarcoma of the prostate in childhood: a case report].
AB  - A case of prostatic rhabdomyosarcoma in an 8-year-old boy is presented. He was
      referred to Kurobe City Hospital with chief complaints of urinary retention and
      fever. Radiologic examinations revealed a huge prostatic tumor. Prostatic needle
      biopsy was performed and the pathological diagnosis was embryonal
      rhabdomyosarcoma of the prostate. He was referred to our hospital and treated
      with chemotherapy consisting of cisplatin, vincristine, cyclophosphamide,
      adriamycin, actinomycin-D and radiotherapy based on the regimen of IRS III. Total
      prostatectomy was performed 6 months after the start of therapy. Viable tumor
      cells were found in the prostate and the left obturator lymph nodes. After the
      operation, we continued chemotherapy. No recurrence was observed 8 months after
      the operation. However, local recurrence occurred in the pelvis 10 months after
      the operation and he died 2 months after the recurrence.

PMID- 9783203
TI  - The ribosome scanning model for translation initiation: implications for gene
      prediction and full-length cDNA detection.
AB  - Biological signals, such as the start of protein translation in eukaryotic mRNA,
      are stretches of nucleotides recognized by cellular machinery. There are a
      variety of techniques for modeling and identifying them. Most of these techniques
      either assume that the base pairs at each position of the signal are
      independently distributed, or they allow for limited dependencies among different
      positions. In previous work, we provided a statistical model that generalizes
      earlier methods and captures all significant high-order dependencies among
      different base positions. In this paper, we use a set of experimentally verified
      translation initiation (TI) sites (provided by Amos Bairoch) from eukaryotic
      sequences to train a range of methods, and then compare these methods. None of
      the methods is effective in predicting TI sites. We take advantage of the
      ribosome scanning model (Cigan et al., 1988) to significantly improve the
      prediction accuracy for full-length mRNAs. The ribosome scanning model suggests
      scanning from the 5' end of the capped mRNA and initiating translation at the
      first AUG in good context. This reduces the search space dramatically and
      accounts for its effectiveness. The success of this approach illustrates how
      biological ideas can illuminate and help solve challenging problems in
      computational biology.

PMID- 9783204
TI  - Compression of strings with approximate repeats.
AB  - We describe a model for strings of characters that is loosely based on the Lempel
      Ziv model with the addition that a repeated substring can be an approximate match
      to the original substring; this is close to the situation of DNA, for example.
      Typically there are many explanations for a given string under the model, some
      optimal and many suboptimal. Rather than commit to one optimal explanation, we
      sum the probabilities over all explanations under the model because this gives
      the probability of the data under the model. The model has a small number of
      parameters and these can be estimated from the given string by an expectation
      maximization (EM) algorithm. Each iteration of the EM algorithm takes O(n2) time
      and a few iterations are typically sufficient. O(n2) complexity is impractical
      for strings of more than a few tens of thousands of characters and a faster
      approximation algorithm is also given. The model is further extended to include
      approximate reverse complementary repeats when analyzing DNA strings. Tests
      include the recovery of parameter estimates from known sources and applications
      to real DNA strings.

PMID- 9783205
TI  - Calculating the exact probability of language-like patterns in biomolecular
      sequences.
AB  - We present algorithms for the exact computation of the probability that a random
      string of a certain length matches a given regular expression. These algorithms
      can be used to determine statistical significance in a variety of pattern
      searches such as motif searches and gene-finding. This work improves upon work of
      Kleffe and Langebacker (Kleffe & Langbecker 1990) and of Sewell and Durbin
      (Sewell & Durbin 1995) in several ways. First, in many cases of interest, the
      algorithms presented here are faster. In addition, the type of pattern considered
      here strictly includes those of both previous works but also allows, for
      instance, arbitrary length gaps. Also, the type of probability model which can be
      used is more general than that of Sewell and Durbin, allowing for Markov chains.
      The problem solved in this work is in fact in the class of NP-hard problems which
      are believed to be intractable. However, the problem is fixed-parameter
      tractable, meaning that it is tractable for small patterns. The is problem is
      also computationally feasible for many patterns which occur in practice. As a
      sample application, we consider calculating the statistical significance of most
      of the PROSITE patterns as in Sewell and Durbin. Whereas their method was only
      fast enough to exactly compute the probabilities for sequences of length 13
      larger than the pattern length, we calculate these probabilities for sequences of
      up to length 2000. In addition, we calculate most of these probabilities using a
      first order Markov chain. Most of the PROSITE patterns have high significance at
      length 2000 under both the i.i.d. and Markov chain models. For further
      applications, we demonstrate the calculation of the probability of a PROSITE
      pattern occurring on either strand of a random DNA sequence of up to 500 kilo
      bases and the probability of a simple gene model occurring in a random sequence
      of up to 1 megabase.

PMID- 9783206
TI  - TAMBIS--Transparent Access to Multiple Bioinformatics Information Sources.
AB  - The TAMBIS project aims to provide transparent access to disparate biological
      databases and analysis tools, enabling users to utilize a wide range of resources
      with the minimum of effort. A prototype system has been developed that includes a
      knowledge base of biological terminology (the biological Concept Model), a model
      of the underlying data sources (the Source Model) and a 'knowledge-driven' user
      interface. Biological concepts are captured in the knowledge base using a
      description logic called GRAIL. The Concept Model provides the user with the
      concepts necessary to construct a wide range of multiple-source queries, and the
      user interface provides a flexible means of constructing and manipulating those
      queries. The Source Model provides a description of the underlying sources and
      mappings between terms used in the sources and terms in the biological Concept
      Model. The Concept Model and Source Model provide a level of indirection that
      shields the user from source details, providing a high level of source
      transparency. Source independent, declarative queries formed from terms in the
      Concept Model are transformed into a set of source dependent, executable
      procedures. Query formulation, translation and execution is demonstrated using a
      working example.

PMID- 9783207
TI  - Computational applications of DNA structural scales.
AB  - We study from a computational standpoint several different physical scales
      associated with structural features of DNA sequences, including dinucleotide
      scales such as base stacking energy and propeller twist, and trinucleotide scales
      such as bendability and nucleosome positioning. We show that these scales provide
      an alternative or complementary compact representation of DNA sequences. As an
      example we construct a strand invariant representation of DNA sequences. The
      scales can also be used to analyze and discover new DNA structural patterns,
      especially in combinations with hidden Markov models (HMMs). The scales are
      applied to HMMs of human promoter sequences revealing a number of significant
      differences between regions upstream and downstream of the transcriptional start
      point. Finally we show, with some qualifications, that such scales are by and
      large independent, and therefore complement each other.

PMID- 9783208
TI  - Advanced query mechanisms for biological databases.
AB  - Existing query interfaces for biological databases are either based on fixed
      forms or textual query languages. Users of a fixed form-based query interface are
      limited to performing some pre-defined queries providing a fixed view of the
      underlying database, while users of a free text query language-based interface
      have to understand the underlying data models, specific query languages and
      application schemas in order to formulate queries. Further, operations on
      application-specific complex data (e.g., DNA sequences, proteins), which are
      usually provided by a variety of software packages with their own format
      requirements and peculiarities, are not available as part of, nor integrated with
      biological query interfaces. In this paper, we describe generic tools that
      provide powerful and flexible support for interactively exploring biological
      databases in a uniform and consistent way, that is via common data models,
      formats, and notations, in the framework of the Object-Protocol Model (OPM).
      These tools include (i) a Java graphical query construction tool with support for
      automatic generation of Web query forms that can be either used for further
      specifying conditions, or can be saved and customized; (ii) query processors for
      interpreting and executing queries that may involve complex application-specific
      objects, and that could span multiple heterogeneous databases and file systems;
      and (iii) utilities for automatic generation of HTML pages containing query
      results, that can be browsed using a Web browser. These tools avoid the
      restrictions imposed by traditional fixed-form query interfaces, while providing
      users with simple and intuitive facilities for formulating ad-hoc queries across
      heterogeneous databases, without the need to understand the underlying data
      models and query languages.

PMID- 9783209
TI  - A statistical theory of sequence alignment with gaps.
AB  - A statistical theory of local alignment algorithms with gaps is presented. Both
      the linear and logarithmic phases, as well as the phase transition separating the
      two phases, are described in a quantitative way. Markov sequences without mutual
      correlations are shown to have scale-invariant alignment statistics. Deviations
      from scale invariance indicate the presence of mutual correlations detectable by
      alignment algorithms. Conditions are obtained for the optimal detection of a
      class of mutual sequence correlations.

PMID- 9783210
TI  - IMGT/LIGM-DB: a systematized approach for ImMunoGeneTics database coherence and
      data distribution improvement.
AB  - IMGT, the international ImMunoGeneTics database (http:(/)/imgt.cnusc.fr:8104),
      created by Marie-Paule Lefranc, Montpellier, France, is an integrated database
      specializing in antigen receptors and MHC of all vertebrate species. IMGT
      includes LIGM-DB, developed for Immunoglobulins and T-cell-receptors. LIGM-DB
      distributes high quality data with an important increment value added by the LIGM
      expert annotations. LIGM-DB accurate immunogenetics data is based on the
      standardization of biological knowledge related to keywords, annotation labels
      and gene identification. The management of such data resulting from biological
      research requires an high flexible implementation to quickly reflect up-to-date
      results, and to integrate new knowledge. We developed a systematized approach and
      defined LIGM-DB systems which manage and realize the major tasks for the database
      survey. In this paper, we will focus on the coherence system, which became
      absolutely crucial to maintain data quality as the database is growing up and as
      the biological knowledge continues to improve, and on the distribution system
      which makes LIGM-DB data easy to access, download and reuse. Efforts have been
      done to improve the data distribution procedures and adapt them to the current
      bioinformatics needs. Recently, we have developed an API which allows Java
      programmers to remotely access and integrate LIGM-DB data in other computer
      environments.

PMID- 9783211
TI  - The LabFlow system for workflow management in large scale biology research
      laboratories.
AB  - LabFlow is a workflow management system designed for large scale biology research
      laboratories. It provides a workflow model in which objects flow from task to
      task under programmatic control. The model supports parallelism, meaning that an
      object can flow down several paths simultaneously, and sub-workflows which can be
      invoked subroutine-style from a task. The system allocates tasks to Unix
      processes to achieve requisite levels of multiprocessing. The system uses the
      LabBase data management system to store workflow-state and laboratory results.
      LabFlow provides a Per15 object-oriented framework for defining workflows, and an
      engine for executing these. The software is freely available.

PMID- 9783212
TI  - Hierarchical minimization with distance and angle constraints.
AB  - The incorporation of experimentally-determined constraints into structure
      prediction methods based on energy minimization leads to both improved
      selectivity with empirical potential functions and structure determination with
      far fewer constraints than are required for distance-geometry calculations. Some
      methods will be described for using both distance and angle constraints with the
      hierarchical minimization algorithm. The simulation is based on a combination of
      Monte Carlo Simulated Annealing and Genetic Algorithm techniques which are
      integrated into a single framework. The selection cycle of the genetic algorithm
      is carried out at the same temperature as the mutations, or alternatively the
      crossover cycle can be considered as a type of Monte Carlo trial move, such that
      each temperature annealing step corresponds to a new generation. The sequence is
      divided up into segments, and the mutation step consists of replacing an entire
      segment with a choice from a pre-selected list. This list is in turn constructed
      from a list of smaller segments, and the number of overall conformations can thus
      be pruned at each level of selection. Results will be shown for test cases using
      a small number of flexible distance constraints used as an additional term in the
      potential, and for restrictions placed on backbone dihedral angles used as an
      additional screening criterion for constructing trial moves.

PMID- 9783213
TI  - BioSim--a new qualitative simulation environment for molecular biology.
AB  - Traditionally, biochemical systems are modelled using kinetics and differential
      equations in a quantitative simulator. However, for many biological processes
      detailed quantitative information is not available, only qualitative or fuzzy
      statements about the nature of interactions. In a previous paper we have shown
      the applicability of qualitative reasoning methods for molecular biological
      regulatory processes. Now, we present a newly developed simulation environment,
      BioSim, that is written in Prolog using constraint logic programming techniques.
      The simulator combines the basic ideas of two main approaches to qualitative
      reasoning and integrates the contents of a molecular biology knowledge base,
      EcoCyc. We show that qualitative reasoning can be combined with automatic
      transformation of contents of genomic databases into simulation models to give an
      interactive modelling system that reasons about the relations and interactions of
      biological entities. This is demonstrated on the glycolytic pathway.

PMID- 9783214
TI  - GeneExpress: a computer system for description, analysis, and recognition of
      regulatory sequences in eukaryotic genome.
AB  - GeneExpress system has been designed to integrate description, analysis, and
      recognition of eukaryotic regulatory sequences. The system includes 5 basic
      units: (1) GeneNet contains an object-oriented database for accumulation of data
      on gene networks and signal transduction pathways and a Java-based viewer that
      allows an exploration and visualization of the GeneNet information; (2)
      Transcription Regulation combines the database on transcription regulatory
      regions of eukaryotic genes (TRRD) and TRRD Viewer; (3) Transcription Factor
      Binding Site Recognition contains a compilation of transcription factor binding
      sites (TFBSC) and programs for their analysis and recognition; (4) mRNA
      Translation is designed for analysis of structural and contextual features of
      mRNA 5'UTRs and prediction of their translation efficiency; and (5) ACTIVITY is
      the module for analysis and site activity prediction of a given nucleotide
      sequence. Integration of the databases in the GeneExpress is based on the
      Sequence Retrieval System (SRS) created in the European Bioinformatics Institute.

PMID- 9783215
TI  - Modeling protein homopolymeric repeats: possible polyglutamine structural motifs
      for Huntington's disease.
AB  - We describe a prototype system (Poly-X) for assisting an expert user in modeling
      protein repeats. Poly-X reduces the large number of degrees of freedom required
      to specify a protein motif in complete atomic detail. The result is a small
      number of parameters that are easily understood by, and under the direct control
      of, a domain expert. The system was applied to the polyglutamine (poly-Q) repeat
      in the first exon of huntingtin, the gene implicated in Huntington's disease. We
      present four poly-Q structural motifs: two poly-Q beta-sheet motifs (parallel and
      antiparallel) that constitute plausible alternatives to a similar previously
      published poly-Q beta-sheet motif, and two novel poly-Q helix motifs (alpha-helix
      and pi-helix). To our knowledge, helical forms of polyglutamine have not been
      proposed before. The motifs suggest that there may be several plausible
      aggregation structures for the intranuclear inclusion bodies which have been
      found in diseased neurons, and may help in the effort to understand the
      structural basis for Huntington's disease.

PMID- 9783216
TI  - Segment-based scores for pairwise and multiple sequence alignments.
AB  - In this paper, we discuss a novel scoring scheme for sequence alignments. The
      score of an alignment is defined as the sum of so-called weights of aligned
      segment pairs. A simple modification of the weight function used by the original
      version of the DIALIGN alignment program turns out to have a crucial advantage:
      it can be applied to both, global and local alignment problems without the need
      to specify a threshold parameter.

PMID- 9783217
TI  - Prediction of signal peptides and signal anchors by a hidden Markov model.
AB  - A hidden Markov model of signal peptides has been developed. It contains
      submodels for the N-terminal part, the hydrophobic region, and the region around
      the cleavage site. For known signal peptides, the model can be used to assign
      objective boundaries between these three regions. Applied to our data, the length
      distributions for the three regions are significantly different from
      expectations. For instance, the assigned hydrophobic region is between 8 and 12
      residues long in almost all eukaryotic signal peptides. This analysis also makes
      obvious the difference between eukaryotes, Gram-positive bacteria, and Gram
      negative bacteria. The model can be used to predict the location of the cleavage
      site, which it finds correctly in nearly 70% of signal peptides in a cross
      validated test--almost the same accuracy as the best previous method. One of the
      problems for existing prediction methods is the poor discrimination between
      signal peptides and uncleaved signal anchors, but this is substantially improved
      by the hidden Markov model when expanding it with a very simple signal anchor
      model.

PMID- 9783218
TI  - Bayesian protein family classifier.
AB  - A Bayesian procedure for the simultaneous alignment and classification of
      sequences into subclasses is described. This Gibbs sampling algorithm iterates
      between an alignment step and a classification step. It employs Bayesian
      inference for the identification of the number of conserved columns, the number
      of motifs in each class, their size, and the size of the classes. Using Bayesian
      prediction, inter-class differences in all these variables are brought to bare on
      the classification. Application to a superfamily of cyclic nucleotide-binding
      proteins identifies both similarities and differences in the sequence
      characteristics of the five subclasses identified by the procedure: 1) cNMP
      dependent kinases, 2) prokaryotic cAMP-dependent regulatory proteins, CRP-type,
      3) prokaryotic regulatory proteins, FNR-type, 4) cAMP gated ion channel proteins
      of animals, and 5) cAMP gated ion channels of plants.

PMID- 9783219
TI  - Sequence assembly validation by multiple restriction digest fragment coverage
      analysis.
AB  - DNA sequence analysis depends on the accurate assembly of fragment reads for the
      determination of a consensus sequence. This report examines the possibility of
      analyzing multiple, independent restriction digests as a method for testing the
      fidelity of sequence assembly. A dynamic programming algorithm to determine the
      maximum likelihood alignment of error prone electrophoretic mobility data to the
      expected fragment mobilities given the consensus sequence and restriction enzymes
      is derived and used to assess the likelihood of detecting rearrangements in
      genomic sequencing projects. The method is shown to reliably detect errors in
      sequence fragment assembly without the necessity of making reference to an
      overlying physical map. An html form-based interface is available at
      http:/(/)www.ibc.wustl.edu/services/validate. html.

PMID- 9783220
TI  - A surface measure for probabilistic structural computations.
AB  - Computing three-dimensional structures from sparse experimental constraints
      requires method for combining heterogeneous sources of information, such as
      distances, angles, and measures of total volume, shape, and surface. For some
      types of information, such as distances between atoms, numerous methods are
      available for computing structures that satisfy the provided constraints. It is
      more difficult, however, to use information about the degree to which an atom is
      on the surface or buried as a useful constraint during structure computations.
      Surface measures have been used as accept/reject criteria for previously computed
      structures, but this is not an efficient strategy. In this paper, we investigate
      the efficacy of applying a surface measure in the computation of molecular
      structure, using a method of probabilistic least square computations which
      facilitates the introduction of multiple, noisy, heterogeneous data sources. For
      this purpose, we introduce a simple purely geometrical measure of surface
      proximity called maximal conic view (MCV). MCV is efficiently computable and
      differentiable, and is hence well suited to driving a structural optimization
      method based, in part, on surface data. As an initial validation, we show that
      MCV correlates well with known measures for total exposed surface area. We use
      this measure in our experiments to show that information about surface proximity
      (derived from theory or experiment, for example) can be added to a set of
      distance measurements to increase significantly the quality of the computed
      structure. In particular, when 30 to 50 percent of all possible short-range
      distances are provided, the addition of surface information improves the quality
      of the computed structure (as measured by RMS fit) by as much as 80 percent. Our
      results demonstrate that knowledge of which atoms are on the surface and which
      are buried can be used as a powerful constraint in estimating molecular
      structure.

PMID- 9783221
TI  - Identification of divergent functions in homologous proteins by induction over
      conserved modules.
AB  - Homologous proteins do not necessarily exhibit identical biochemical function.
      Despite this fact, local or global sequence similarity is widely used as an
      indication of functional identity. Of the 1327 Enzyme Commission defined
      functional classes with more than one annotated example in the sequence
      databases, similarity scores alone are inadequate in 251 (19%) of the cases. We
      test the hypothesis that conserved domains, as defined in the ProDom database,
      can be used to discriminate between alternative functions for homologous proteins
      in these cases. Using machine learning methods, we were able to induce correct
      discriminators for more than half of these 251 challenging functional classes.
      These results show that the combination of modular representations of proteins
      with sequence similarity improves the ability to infer function from sequence
      over similarity scores alone.

PMID- 9783222
TI  - Phylogenetic inference in protein superfamilies: analysis of SH2 domains.
AB  - This work focuses on the inference of evolutionary relationships in protein
      superfamilies, and the uses of these relationships to identify key positions in
      the structure, to infer attributes on the basis of evolutionary distance, and to
      identify potential errors in sequence annotations. Relative entropy, a distance
      metric from information theory, is used in combination with Dirichlet mixture
      priors to estimate a phylogenetic tree for a set of proteins. This method infers
      key structural or functional positions in the molecule, and guides the tree
      topology to preserve these important positions within subtrees. Minimum
      description-length principles are used to determine a cut of the tree into
      subtrees, to identify the subfamilies in the data. This method is demonstrated on
      SH2-domain containing proteins, resulting in a new subfamily assignment for Src2
      drome and a suggested evolutionary relationship between Nck_human and Drk_drome,
      Sem5_caeel, Grb2_human and Grb2_chick.

PMID- 9783223
TI  - A hidden Markov model for predicting transmembrane helices in protein sequences.
AB  - A novel method to model and predict the location and orientation of alpha helices
      in membrane-spanning proteins is presented. It is based on a hidden Markov model
      (HMM) with an architecture that corresponds closely to the biological system. The
      model is cyclic with 7 types of states for helix core, helix caps on either side,
      loop on the cytoplasmic side, two loops for the non-cytoplasmic side, and a
      globular domain state in the middle of each loop. The two loop paths on the non
      cytoplasmic side are used to model short and long loops separately, which
      corresponds biologically to the two known different membrane insertions
      mechanisms. The close mapping between the biological and computational states
      allows us to infer which parts of the model architecture are important to capture
      the information that encodes the membrane topology, and to gain a better
      understanding of the mechanisms and constraints involved. Models were estimated
      both by maximum likelihood and a discriminative method, and a method for
      reassignment of the membrane helix boundaries were developed. In a cross
      validated test on single sequences, our transmembrane HMM, TMHMM, correctly
      predicts the entire topology for 77% of the sequences in a standard dataset of 83
      proteins with known topology. The same accuracy was achieved on a larger dataset
      of 160 proteins. These results compare favourably with existing methods.

PMID- 9783224
TI  - A computational system for modelling flexible protein-protein and protein-DNA
      docking.
AB  - A computational system is described that predicts the structure of
      protein/protein and protein/DNA complexes starting from unbound coordinate sets.
      The approach is (i) a global search with rigid-body docking for complexes with
      shape complementarity and favourable electrostatics; (ii) use of distance
      constraints from experimental (or predicted) knowledge of critical residues;
      (iii) use of pair potential to screen docked complexes and (iv) refinement and
      further screening by protein-side chain optimisation and interfacial energy
      minimisation. The system has been applied to model ten protein/protein and eight
      protein-repressor/DNA (steps i to iii only) complexes. In general a few
      complexes, one of which is close to the true structure, can be generated.

PMID- 9783225
TI  - Genetic algorithms for protein threading.
AB  - Despite many years of efforts, a direct prediction of protein structure from
      sequence is still not possible. As a result, in the last few years researchers
      have started to address the "inverse folding problem": Identifying and aligning a
      sequence to the fold with which it is most compatible, a process known as
      "threading". In two meetings in which protein folding predictions were
      objectively evaluated, it became clear that threading as a concept promises a
      real breakthrough, but that much improvement is still needed in the technique
      itself. Threading is a NP-hard problem, and thus no general polynomial solution
      can be expected. Still a practical approach with demonstrated ability to find
      optimal solutions in many cases, and acceptable solutions in other cases, is
      needed. We applied the technique of Genetic Algorithms in order to significantly
      improve the ability of threading algorithms to find the optimal alignment of a
      sequence to a structure, i.e. the alignment with the minimum free energy. A major
      progress reported here is the design of a representation of the threading
      alignment as a string of fixed length. With this representation validation of
      alignments and genetic operators are effectively implemented. Appropriate data
      structure and parameters have been selected. It is shown that Genetic Algorithm
      threading is effective and is able to find the optimal alignment in a few test
      cases. Furthermore, the described algorithm is shown to perform well even without
      pre-definition of core elements. Existing threading methods are dependent on such
      constraints to make their calculations feasible. But the concept of core elements
      is inherently arbitrary and should be avoided if possible. While a rigorous proof
      is hard to submit yet an, we present indications that indeed Genetic Algorithm
      threading is capable of finding consistently good solutions of full alignments in
      search spaces of size up to 10(70).

PMID- 9783226
TI  - Automated clustering and assembly of large EST collections.
AB  - The availability of large EST (Expressed Sequence Tag) databases has led to a
      revolution in the way new genes are cloned. Difficulties arise, however, due to
      high error rates and redundancy of raw EST data. For these reasons, one of the
      first tasks performed by a scientist investigating any EST of interest is to
      gather contiguous ESTs and assemble them into a larger virtual cDNA. The REX
      (Recursive EST eXtender) algorithm described in this paper completely automates
      this process by finding ESTs that can be clustered on the basis of overlapping
      bases, and then assembling the contigs into a consensus sequence. By combining
      the clustering and assembly steps, REX can quickly generate assemblies from EST
      databases that are frequently updated without having to preprocess the data. A
      consensus assembly method is used to correct miscalled bases and remove indel
      errors. A unique feature of this method is that it addresses the issues of splice
      variants and unspliced cDNA data. Since REX is a fast greedy algorithm, it can
      address the problem of generating a database of assembled sequences from very
      large collections of EST data. A procedure is described for creating and
      maintaining an Assembled Consensus EST database (ACE) that is useful for
      characterizing the large body of data that exists in EST databases.

PMID- 9783227
TI  - A map of the protein space--an automatic hierarchical classification of all
      protein sequences.
AB  - We investigate the space of all protein sequences. We combine the standard
      measures of similarity (SW, FASTA, BLAST), to associate with each sequence an
      exhaustive list of neighboring sequences. These lists induce a (weighted
      directed) graph whose vertices are the sequences. The weight of an edge
      connecting two sequences represents their degree of similarity. This graph
      encodes much of the fundamental properties of the sequence space. We look for
      clusters of related proteins in this graph. These clusters correspond to strongly
      connected sets of vertices. Two main ideas underlie our work: i) Interesting
      homologies among proteins can be deduced by transitivity. ii) Transitivity should
      be applied restrictively in order to prevent unrelated proteins from clustering
      together. Our analysis starts from a very conservative classification, based on
      very significant similarities, that has many classes. Subsequently, classes are
      merged to include less significant similarities. Merging is performed via a novel
      two phase algorithm. First, the algorithm identifies groups of possibly related
      clusters (based on transitivity and strong connectivity) using local
      considerations, and merges them. Then, a global test is applied to identify
      nuclei of strong relationships within these groups of clusters, and the
      classification is refined accordingly. This process takes place at varying
      thresholds of statistical significance, where at each step the algorithm is
      applied on the classes of the previous classification, to obtain the next one, at
      the more permissive threshold. Consequently, a hierarchical organization of all
      proteins is obtained. The resulting classification splits the space of all
      protein sequences into well defined groups of proteins. The results show that the
      automatically induced sets of proteins are closely correlated with natural
      biological families and super families. The hierarchical organization reveals
      finer sub-families that make up known families of proteins as well as many
      interesting relations between protein families. The hierarchical organization
      proposed may be considered as the first map of the space of all protein
      sequences. An interactive web site including the results of our analysis has been
      constructed, and is now accessible through http:/(/)www.protomap.cs.huji.ac.il

PMID- 9783228
TI  - Alterations of per RNA in noncoding regions affect periodicity of circadian
      behavioral rhythms.
AB  - Circadian rhythms in Drosophila depend on a molecular feedback loop that includes
      products of the period (per) and timeless (tim) genes. RNA and protein products
      of both genes cycle with a circadian period and the proteins feedback to inhibit
      expression of their own mRNAs. While cyclic expression of PER protein appears to
      be necessary for rhythmic behavior, the function of per RNA cycling is somewhat
      controversial. Rhythmic transcription accounts, in part, for cycling of per RNA,
      but it is clear now that posttranscriptional mechanisms also contribute to the
      cyclic expression of both per RNA and protein. As posttranscriptional mechanisms,
      such as mRNA stability and translation, are frequently mediated by 3'
      untranslated regions (UTR) of genes, the authors examined the role of this region
      of per in the regulation of circadian rhythms. Removal of most of per's 3' UTR
      had a small effect on the function of a per transgene. However, replacement of
      per's 3'UTR with corresponding sequences of the tubulin gene led to the rescue of
      behavioral rhythms in per01 flies with periods that were 3 h shorter than those
      generated by a wild-type per transgene. The hybrid RNA cycles, but the protein
      produced by it accumulates earlier in a day-night cycle than the PER protein
      produced by a control per transgene carrying its own 3'UTR, perhaps because the
      tubulin sequences counteract the effect of destabilizing elements in the per RNA
      at earlier points in the circadian cycle. These data indicate that the
      appropriate regulation of per RNA expression, effected by transcriptional as well
      as posttranscriptional mechanisms, is critical for the determination of circadian
      period.

PMID- 9783229
TI  - The timSL mutant affects a restricted portion of the Drosophila melanogaster
      circadian cycle.
AB  - The circadian rhythm genes period (per) and timeless (tim) are central to
      contemporary studies on Drosophila circadian rhythms. Mutations in these genes
      give rise to arrhythmic or period-altered phenotypes, and per and tim gene
      expression is under clock control. per and tim proteins (PER and TIM) also
      undergo circadian changes in level and phosphorylation state. The authors
      previously described a period-altering tim mutation, timSL, with allele-specific
      effects in different per backgrounds. This mutation also affected the TIM
      phosphorylation profile during the mid-late night. The authors show here that the
      single amino acid alteration in TIM-SL is indeed responsible for the phenotype,
      as a timSL transgene recapitulates the original mutant phenotype and shortens the
      period of perL flies by 3 h. The authors also show that this mutation has
      comparable effects in a light-dark cycle, as timSL also accelerates the activity
      offset during the mid-late night of perL flies. Importantly, timSL advances
      predominantly the mid-late night region of the perL phase response curve,
      consistent with the notion that this portion of the cycle is governed by unique
      rate-limiting steps. The authors propose that TIM and PER phosphorylation are
      normally rate determining during the mid-late night region of the circadian
      cycle.

PMID- 9783230
TI  - Dual entrainment by light and food in the Svalbard ptarmigan (Lagopus mutus
      hyperboreus).
AB  - The possibility that feeding may act as a zeitgeber has been investigated in
      captive Svalbard ptarmigan by recording feeding or food-searching activity (FA)
      in birds given periodic access to food (PAF) under light-dark (LD) cycles or in
      continuous bright (LL) or dim light (DD) conditions. Except during LL,
      anticipatory attempts to feed always occurred prior to the food access interval
      with a relatively stable phase relationship to the interval. There was always a
      second bout of feeding toward the end of the food access interval, which
      apparently corresponds to the afternoon bout of feeding, seen under LD and ad
      libitum access to food. During PAF, this afternoon peak of activity disappeared.
      When the LD cycle was phase delayed while restricted access to food remained
      unchanged, the afternoon peak of feeding was temporarily reestablished but was
      transiently shifted forward to reattain its position within the food access
      interval. After termination of PAF, the afternoon bout of feeding was
      reestablished through phase-delaying transients, with an initial phase
      corresponding to the previous food access interval. The results suggest that FA
      of Svalbard ptarmigan is controlled by 2 separate circadian oscillators, both of
      which can be entrained by light and food: a putative morning oscillator, which
      controls the activity associated with the beginning of the photoperiod or the
      food access interval, and a putative evening oscillator, which induces increased
      activity toward the end of these intervals. In their natural environment at very
      high latitudes, Svalbard ptarmigan deposit fat when the day length declines
      rapidly in autumn. Entrained by feeding, they appear to enjoy a longer daily
      period of food-searching activity than if day length was the only zeitgeber.

PMID- 9783231
TI  - Daily variations in pineal melatonin concentrations in inbred and outbred mice.
AB  - Melatonin was measured using a specific radioimmunoassay in 1 strain of outbred
      mice (OF1 Swiss) and 4 strains of inbred mice, 2 of them being known to
      synthesize melatonin (CBA and C3H) and the 2 others being controversial (BALB/c
      and C57BL/6). In this study, the 5 mouse strains were able to synthesize
      melatonin, but the basal levels as well as the diurnal variations were very
      different from one strain to another. CBA and C3H strains showed a clear-cut day
      night rhythm of pineal melatonin concentration, with peak levels of 276 +/- 22
      pg/pineal in CBA and 135 +/- 12 pg/pineal in C3H. In BALB/c, the authors
      confirmed the presence of a very short melatonin peak (15 min) in the middle of
      the dark period. In C57BL/6 and OF1 Swiss, a very small but significant peak was
      observed in the middle of the darkness. In the former, another small peak was
      also observed at light onset. Whether these very small peaks, which may be
      related to the deficience of N-acetyl transferase activity reported by others,
      have a physiological meaning remains to be determined.

PMID- 9783232
TI  - Roles of suprachiasmatic nuclei and intergeniculate leaflets in mediating the
      phase-shifting effects of a serotonergic agonist and their photic modulation
      during subjective day.
AB  - Serotonin (5-HT) has been implicated in the phase adjustment of the circadian
      system during the subjective day in response to nonphotic stimuli. Two components
      of the circadian system, the suprachiasmatic nucleus (SCN) (site of the circadian
      clock) and the intergeniculate leaflet (IGL), receive serotonergic projections
      from the median raphe nucleus and the dorsal raphe nucleus, respectively.
      Experiment 1, performed in golden hamsters housed in constant darkness, compared
      the effects of bilateral microinjections of the 5-HT1A/7 receptor agonist, 8
      hydroxydipropylaminotetralin (8-OH-DPAT; 0.5 microgram in 0.2 microliter saline
      per side), into the IGL or the SCN during the mid-subjective day. Bilateral 8-OH
      DPAT injections into either the SCN or the IGL led to significant phase advances
      of the circadian rhythm of wheel-running activity (p < .001). The phase advances
      following 8-OH-DPAT injections in the IGL were dose department (p < .001).
      Because a light pulse administered during the middle of the subjective day can
      attenuate the phase-resetting effect of a systemic injection of 8-OH-DPAT,
      Experiment 2 was designed to determine whether light could modulate 5-HT agonist
      activity at the level of the SCN and/or the IGL. Serotonergic receptor activation
      within the SCN, followed by a pulse of light (300 lux of white light lasting 30
      min), still induced phase advances. In contrast, the effect of serotonergic
      stimulation within the IGL was blocked by a light pulse. These results indicate
      that the respective 5-HT projections to the SCN and IGL subserve different
      functions in the circadian responses to photic and nonphotic stimuli.

PMID- 9783233
TI  - Circadian food anticipation persists in capsaicin deafferented rats.
AB  - The feeding-entrained circadian oscillator (FEO) organizes locomotor activity and
      other variables to anticipate daily timed meals. Whether the biological substrate
      for the FEO is in the central nervous system or in the periphery, there must be
      communication between the gut and the brain to result in a behavioral output. To
      investigate potential neural routes of communication, rats with suprachiasmatic
      lesions were given systemic capsaicin (total dose: 100 mg/kg, i.p.) to produce
      visceral deafferentation. Deafferentation was confirmed using the phenyl-p
      benzoquinone stretch test and the corneal irritation test. A 3-h meal was made
      available at the same time each day while wheel running was recorded for several
      weeks. Results indicated that rats with capsaicin lesions were somewhat more
      active overall and during nonanticipation times, but the onset time and the
      amount of anticipatory wheel running did not differ from vehicle-treated
      controls. In addition, reentrainment following a phase delay of mealtime and the
      persistence of anticipatory activity during food deprivation were similar between
      the groups. Since capsaicin deafferentation and subdiaphragmatic vagotomy do not
      prevent food-anticipatory activity, it is likely that communication between the
      gut and the brain is accomplished via a humoral route.

PMID- 9783234
TI  - The significance of circadian organization for longevity in the golden hamster.
AB  - While functional roles for biological clocks have been demonstrated in organisms
      throughout phylogeny, the adaptive advantages of circadian organization per se
      are largely matters of conjecture. It is generally accepted, though without
      direct experimental evidence, that organisms derive primary benefits from the
      temporal organization of their physiology and behavior, as well as from the
      anticipation of daily changes in their environment and their own fluctuating
      physiological requirements. However, the consequences of circadian dysfunction
      that might demonstrate a primary adaptive advantage and explain the natural
      origins and apparent ubiquity of circadian systems have not been documented. The
      authors report that longevity in hamsters is decreased with a noninvasive
      disruption of rhythmicity and is increased in older animals given suprachiasmatic
      implants that restore higher amplitude rhythms. The results substantiate the
      importance of the temporal organization of physiology and behavior provided by
      the circadian clock to the health and longevity of an organism.

PMID- 9783235
TI  - Human perception of short and long time intervals: its correlation with body
      temperature and the duration of wake time.
AB  - Time estimation was studied in seven human subjects during prolonged sojourn is
      isolation from time cues. They wore rectal temperature probes throughout the
      experiments, and during wakefulness recorded each time they thought one hour had
      passed. At the end of each of these subjective hours they produced a subjective 5
      or 10 sec interval. The produced intervals on the 1-h task were not related to
      body temperature but were correlated with and proportional to the duration of
      waketime in all subjects. The produced 5 and 10 sec intervals were in all
      subjects negatively correlated with rectal temperature, but were not associated
      with wake time. Brief and long time intervals are subjectively experienced via
      different mechanisms.

PMID- 9783236
TI  - [Absence of induced spasm by intracoronary injection of 50 micrograms
      acetylcholine in the right coronary artery: usefulness of 80 micrograms of
      acetylcholine as a spasm provocation test].
AB  - This study investigated whether the maximal dose of 50 micrograms acetylcholine
      for the induction of coronary spasm in the right coronary artery is adequate. The
      acetylcholine test was performed in 388 consecutive patients to evaluate spasm
      from January 1994 to December 1997. Coronary spasm in the right coronary artery
      was induced in 43 patients, 37 men and 6 women with a mean age of 63 +/- 8 years
      by intracoronary injection of 80 micrograms of acetylcholine rather than 50
      micrograms. These included 15 patients (35%) with rest angina, 23 patients with
      ischemic heart disease other than rest angina and 5 patients (12%) with non
      ischemic heart disease. Acetylcholine was injected in incremental doses of 20, 50
      and 80 micrograms into the right coronary artery. Positive spasm was defined as
      induction of more than 90% reversible narrowing associated with either usual
      chest pain or ischemic electrocardiographic changes. Clinical and angiographical
      characteristics was studied in these patients. Fifteen (35%) patients had rest
      angina and 4 patients had variant angina with ST elevation in the inferior leads.
      Two thirds of the patients had coronary spasm in the distal portion of the right
      coronary artery and one third of those disclosed spasm focally. Coronary spasm
      was induced in 38 (15%) of 246 patients with ischemic heart disease and in 5 (4%)
      of 142 patients with non-ischemic heart disease. The prevalence of positive spasm
      in patients with ischemic heart disease was significantly higher (p < 0.01) than
      in patients with non-ischemic heart disease. A dose of 80 micrograms of
      acetylcholine, more than the maximal standard dose, might be clinically useful
      for the induction of spasm in the right coronary artery if coronary spasm of this
      artery is strongly suspected.

PMID- 9783237
TI  - [Detection of coronary artery disease by adenosine triphosphate stress
      echocardiography: comparison with adenosine triphosphate stress thallium
      myocardial scintigraphy and coronary angiography].
AB  - The clinical feasibility and usefulness of adenosine triphosphate-2Na (ATP)
      stress echocardiography for the detection of coronary artery disease (CAD) were
      assessed. Two-dimensional echocardiography and thallium-201 single photon
      emission computed tomography (SPECT) during ATP infusion were performed
      simultaneously in 58 consecutive patients (41 men and 17 women; mean age 66 +/-
      12 years) with suspected CAD. ATP was infused intravenously at 0.16 mg/kg/min for
      5 min and thallium was injected at 4 min. All patients underwent coronary
      angiography within 2 weeks of ATP echocardiography and ATP SPECT. An ischemic
      response during ATP infusion was detected by echocardiography as the development
      or worsening of a wall motion abnormality compared with the baseline and by SPECT
      as a perfusion defect that filled totally or partially during redistribution.
      Significant coronary artery stenosis was defined as > or = 75% diameter stenosis
      in a major epicardial vessel. The severity of the stenosis was classified as
      follows: Group A, lesions with significant coronary artery stenosis (> or = 75%,
      < 90%); Group B, lesions with severe coronary artery stenosis (> or = 90%)
      without collateral circulation; Group C, lesions with severe coronary artery
      stenosis (> or = 90%) with collateral circulation. Significant CAD was present in
      43 of 58 patients. The overall sensitivity, specificity and accuracy of ATP
      echocardiography for detecting significant CAD were 70%, 100% and 78%,
      respectively, and those of ATP SPECT were 98%, 87% and 95%, respectively. In
      patients without previous myocardial infarction, the sensitivity of ATP
      echocardiography was 67%. The sensitivity of ATP echocardiography and ATP SPECT
      for detecting myocardial ischemia were 59% and 95% in patients with 1-vessel
      disease, 75% and 100% in those with 2-vessel disease, and 88% and 100% in those
      with 3-vessel disease, respectively. The induction of wall motion abnormality by
      ATP echocardiography was highly concordant with ATP SPECT imaging in patients
      with multivessel disease. Although the sensitivity of ATP echocardiography
      improved in patients with multivessel disease more than in those with single
      vessel disease, detection of all diseased vessels was achieved in only 10% of
      patients with multivessel disease. The sensitivity of ATP echocardiography and
      ATP SPECT for detecting myocardial ischemia in individual vessels were: right
      coronary artery, 58% and 74%; left anterior descending artery, 59% and 97%; left
      circumflex artery, 27% and 68%. ATP-induced transient perfusion defects were
      associated with transient wall motion abnormality in only 57% of segments. The
      sensitivity of ATP echocardiography and ATP SPECT for detecting myocardial
      ischemia in patients with severe coronary stenosis were: Group A, 32% and 66%;
      Group B, 60% and 93%; Group C, 80% and 95%. The sensitivity of ATP
      echocardiography was significantly higher in the lesions with collateral
      circulation than in those without collateral circulation. ATP stress
      echocardiography is useful for detecting myocardial ischemia in patients with
      multivessel disease and in patients with severe coronary artery stenosis (> or =
      90%). In particular, transient wall motion abnormality tends to be detected in
      the segments perfused by collateral circulation.

PMID- 9783238
TI  - Comparison of percentage area of myocardial fibrosis and disarray in patients
      with classical form and dilated phase of hypertrophic cardiomyopathy.
AB  - This study compared the percentage area of myocardial fibrosis and disarray
      between hypertrophic cardiomyopathy (HCM) and DHCM (progression to dilatation of
      the left ventricle in patients with HCM, i.e., dilated phase HCM), and
      investigated whether DHCM is included in the natural course of HCM. Twenty-six
      autopsied hearts were studied, 14 from patients with HCM, and 12 from patients
      with DHCM, classified by age/decade group. The section at the level of the
      binding site of papillary muscle was used for the morphometrical examination. In
      the overall evaluation of both ventricles, all 4 HCM age groups showed percentage
      area of myocardial fibrosis < 10%, and the value gradually increased with age. In
      contrast, the percentage area of the DHCM cases was over 20%, and these cases
      showed diffuse massive fibrosis that did not increase with age. The percentage
      area of myocardial disarray was over 90% in 3 cases with DHCM. The percentage
      areas of myocardial fibrosis and disarray of the DHCM hearts were extremely high
      compared with the HCM hearts, indicating that DHCM is not included in natural
      course of HCM. Other abnormalities including contractile proteins may be
      important role in the widespread myocardial disarray leading to massive fibrosis
      in the pathogenesis of DHCM.

PMID- 9783239
TI  - [Color M-mode Doppler analysis of left ventricular inflow in pediatric patients].
AB  - This study evaluated the clinical usefulness of analyzing left ventricular (LV)
      filling by color M-mode Doppler echocardiography in pediatric patients. The LV
      filling patterns of color M-mode Doppler echocardiography were obtained by LV
      inflow in the apical 4-chamber or long-axis view, and the time difference between
      the occurrence of peak velocity at the mitral tip and in the apical region (M-AP)
      was calculated. The peak velocity at each depth was determined by adequate
      selection of the Nyquist limit by shifting the zero point after freezing the
      color M-mode. LV volume and posterior wall motion velocity were obtained
      simultaneously. The catheter-derived data were compared with echo-derived data in
      7 patients (mean age 12.0 years). The M-AP correlated positively with the time
      constant of LV relaxation (tau; r = 0.83, p < 0.05), pulmonary capillary wedge
      pressure (r = 0.83, p < 0.05), and negatively with peak diastolic posterior wall
      motion velocity (r = -0.78, p < 0.05). The M-AP was compared with other echo
      derived data between Group N (35 children with normal cardiac function, mean age
      4.3 years) and Group F (12 children with LV ejection fraction less than 40%, mean
      age 9.5 years). The M-AP was significantly longer in Group F (53.3 +/- 14.0 vs
      116.5 +/- 30.5 msec; p < 0.001), but there was no significant difference in the
      E/A or deceleration time of E between the 2 groups. In Group N, the E/A
      correlated to LV end-diastolic volume and heart rate, but the M-AP showed no
      correlation. In Group F, the M-AP correlated with the percentages of normal LV
      end-diastolic volume (r = 0.76, p < 0.01) and LV ejection fraction (r = -0.58, p
      < 0.05). The M-AP was not influenced by LV size or heart rate and could easily
      differentiate normal heart from failing heart, and thus this is a useful
      parameter for evaluating diastolic function in pediatric patients.

PMID- 9783240
TI  - [Abnormalities of electrocardiographic P wave morphology and the relationship to
      electrophysiological parameters of the atrium in patients with idiopathic
      paroxysmal atrial fibrillation].
AB  - In 39 patients with idiopathic paroxysmal atrial fibrillation (PAF group), the
      incidence of the abnormal P wave morphology (prolonged P wave and mitral P in
      lead II and increased P terminal force in lead V1: PTF V1) was examined, and the
      relationships to the electrophysiologic findings of the atrial muscle were
      investigated. The control group consisted of 42 patients with various cardiac
      arrhythmias other than sick sinus syndrome. P wave duration was significantly
      longer in the PAF group than in the control group (112 +/- 12 vs 98 +/- 10 msec,
      p < 0.0001). PTF V1 was greater in the PAF group than in the control group (0.051
      +/- 0.018 vs 0.028 +/- 0.010 msec, p < 0.0001). P mitrale occurred in only 5
      patients (12%) in the control group as compared to 25 patients in the PAF group
      (64%, p < 0.0001). The longest duration of the right atrial electrograms was
      longer in the PAF group than in the control group (101 +/- 17 vs 85 +/- 10 msec,
      p < 0.0001), as was the maximal number of the fragmented deflections (8.0 +/- 2.5
      vs 5.8 +/- 1.4, p < 0.0001). Repetitive atrial firing zone and also fragmented
      atrial activity zone were longer in the PAF group than in the control group (34
      +/- 24 vs 12 +/- 19 msec, p < 0.02 and 47 +/- 27 vs 24 +/- 19 msec, p < 0.001,
      respectively). Interatrial conduction delay zone was longer in the PAF group than
      in the control group (55 +/- 25 vs 38 +/- 18 msec, p < 0.001). P wave duration
      and PTF V1 had significant and/or borderline correlations with the longest
      duration of the right atrial electrocardiograms (r = 0.75, p < 0.0001 and r =
      0.68, p < 0.0001, respectively), and the maximal number of its fragmented
      defections (r = 0.50, p < 0.002 and r = 0.40, p < 0.05, respectively).
      Furthermore, P wave duration had a correlation with the repetitive atrial firing
      zone (r = 0.55, p < 0.01). Prolonged P wave duration and increased PTF V1 are
      electrocardiographic indicators for the coexistence of electrophysiologic
      abnormalities in patients with idiopathic paroxysmal atrial fibrillation.

PMID- 9783241
TI  - Electrical and mechanical abnormalities in the heart of a schizophrenic patient
      with hyponatremia derived from water intoxication.
AB  - Electrical and mechanical abnormalities were studied in the heart of a
      schizophrenic male patient with severe hyponatremia and concomitant low plasma
      osmolarity induced by excessive water intake (so-called "water intoxication
      syndrome") by recording electrocardiography and echocardiography. There was a
      significant positive correlation between the plasma osmolarity and serum sodium
      concentration. The QRS duration of electrocardiography, an index of the
      ventricular electrical conduction velocity, tended to be prolonged and the left
      ventricular ejection fraction calculated by echocardiography decreased in
      proportion to the reduction of the serum sodium concentration. Lowering
      extracellular sodium concentration theoretically slows electrical conduction
      velocity, and was observed in this patient. On the other hand, low external
      sodium concentration should increase cardiac contractility via suppression of the
      forward mode operation of the sodium-calcium exchange mechanism, thereby
      increasing the intracellular free calcium concentration. However, this was not
      the case in our patient, because ejection fraction was not increased but rather
      significantly decreased with the lowering of serum sodium concentration. We
      speculate that in patients with water intoxication, the negative inotropism of
      the heart caused by low plasma osmolarity prevails over the positive inotropism
      caused by low serum sodium concentration.

PMID- 9783242
TI  - [Cardiovascular imaging in-a-month. A 67-year-old man with recurrent fever after
      permanent pacemaker replacement. Vegetation on the permanent pacemaker lead].

PMID- 9783243
TI  - Umbilical artery blood flow velocity in pregnancies complicated by systemic lupus
      erythematosus.
AB  - PURPOSE: We evaluated the role of umbilical artery Doppler velocimetry in the
      surveillance of pregnancies complicated by systemic lupus erythematosus (SLE).
      METHODS: We retrospectively studied 56 women with SLE whose pregnancies were
      managed at our perinatal center between 1988 and 1995. RESULTS: Absent or
      reversed end-diastolic flow velocity was detected in 6 (11%) of 56 patients. This
      sub-group of patients had an increased risk of pre-eclampsia, intrauterine growth
      restriction, cesarean section, and preterm delivery. CONCLUSIONS: A high
      incidence (11%) of abnormal umbilical artery waveforms was detected. This finding
      was associated with an increased risk of maternal and fetal complications.

PMID- 9783244
TI  - Cervical lymphadenopathy: sonographic differentiation between tuberculous nodes
      and nodal metastases from non-head and neck carcinomas.
AB  - PURPOSE: Clinical examination alone cannot differentiate between cervical
      tuberculous lymphadenitis and cervical nodal metastases from non-head and neck
      (NHN) carcinomas because the distributions of involved lymph nodes are similar.
      We evaluated the sonographic features of cervical lymph nodes that could be used
      to differentiate between the 2 categories of nodes. METHODS: We retrospectively
      reviewed sonograms of abnormal cervical lymph nodes in 47 patients with proven
      cervical tuberculous lymphadenitis and in 22 patients with proven nodal
      metastases from NHN carcinomas. RESULTS: Abnormal nodes in tuberculous
      lymphadenitis and nodal metastases from NHN carcinomas were commonly found in the
      supraclavicular fossa (15% and 38%, respectively) and the posterior triangle (70%
      and 41%, respectively). Statistically significant (p < 0.05) features for
      differential diagnosis were lymph nodes' longest diameter, echogenicity, short-to
      long axis ratio, appearance of surrounding soft tissues, and presence of
      intranodal cystic necrosis, matting, and posterior enhancement. Nodal size,
      echogenicity, presence of an echogenic hilum, calcification, coagulation
      necrosis, and sharpness of borders helped in identifying the abnormal lymph
      nodes. CONCLUSIONS: Sonographic features that helped to differentiate between the
      2 categories of nodes were shape, edema of surrounding soft tissue, homogeneity,
      intranodal cystic necrosis, matting, and posterior enhancement.

PMID- 9783245
TI  - Size of pancreas in children and adolescents with type I (insulin-dependent)
      diabetes.
AB  - PURPOSE: The aim of this study was to evaluate the influence of insulin-dependent
      diabetes mellitus (IDDM) on the size of the pancreas in children. METHODS:
      Pancreas size was evaluated sonographically in a group of 60 diabetic children
      and adolescents, aged 3-15 years, and 60 sex- and age-matched healthy controls.
      RESULTS: A significant reduction in pancreatic area and other parameters was
      found in diabetic patients particularly in children aged 8-12 and 13-15 years.
      The pancreas was larger in children 3-7 years old who had had IDDM for 2 years of
      less (mean size, 8.61 cm2) than in children 8-12 and 13-15 years old who had had
      IDDM for more than 5 years (mean size, 8.06 and 8.40 cm2, respectively). An
      inverse correlation between area of the pancreas and duration of IDDM was seen in
      all age groups (p < 0.05). CONCLUSIONS: Diabetes affects the growth of the
      pancreas in children with IDDM. Sonography can be used to noninvasively evaluate
      the influence of the disease on pancreas size.

PMID- 9783246
TI  - Value of abdominal sonography in the assessment of children with abdominal pain.
AB  - PURPOSE: We retrospectively evaluated the usefulness of sonography in the
      diagnostic assessment of children with abdominal pain. METHODS: From July 1988 to
      October 1996, 676 children who had abdominal pain and were referred for
      sonography underwent abdominal and pelvic sonographic examination. Of these, 644
      children had recurrent abdominal pain (RAP) and 32 children had acute or subacute
      abdominal pain (ASAP). The mean ages and relative risks of underlying
      abnormalities were calculated for children with RAP and ASAP. RESULTS: Abdominal
      abnormalities were sonographically detected in 10 children with RAP (2%), a
      significantly lower incidence than in children with ASAP (56%, p < 0.0001), with
      a relative risk of 0.028 (95% CI, 0.014-0.055). In the RAP group, an underlying
      abnormality was more likely (p < 0.001) to be sonographically detected in
      children who had atypical clinical features (5 of 46%; 11%) than in those with
      typical clinical features (5 of 598; 1%), with a relative risk of 12.94 (95% CI,
      3.90-43.30). Children with RAP were found to have hydronephrosis (3), urinary
      cystitis (2), duplex kidney (1), hypoplastic low-lying kidney (1), choledochal
      cyst (1), ovarian teratoma (1), and gross gaseous distention with fecal masses
      (1). Children with ASAP had urinary cystitis (4), intussusception (2),
      appendicitis (2), appendiceal abscess (1), perforated gut with ascites (1), gut
      duplication (1), thickened gut wall with fluid from severe gastroenteritis (1),
      gross gaseous distention with fecal masses (1), hepatosplenomegaly (1),
      cholecystitis (1), gross hydronephrosis (1), Wilms' tumor (1), and abdominal
      neuroblastoma (1). CONCLUSIONS: Abdominal sonography is useful in children with
      ASAP. Although an underlying abnormality was rarely found in children with RAP,
      children who have RAP with atypical clinical features should have sonographic
      screening. If no abnormalities are found, the normal sonograms may be reassuring
      to parents.

PMID- 9783248
TI  - Vasa previa: prenatal diagnosis by transperineal sonography with Doppler
      evaluation.
AB  - Antepartum diagnosis of vasa previa is of critical importance because of the high
      fetal mortality rate in unrecognized cases. This report describes the sonographic
      findings in 2 cases of vasa previa and demonstrates that transperineal sonography
      with Doppler evaluation can successfully establish the diagnosis of vasa previa
      prenatally.

PMID- 9783247
TI  - Duplex sonographic evaluation of the sapheno-femoral venous junction in patients
      with recurrent varicose veins after surgical treatment.
AB  - PURPOSE: We used duplex sonography in patients with recurrent varicose veins
      after surgical treatment to detect any residual stump of the great saphenous vein
      at the sapheno-femoral venous junction, and we compared these sonographic
      findings with surgical findings as the "gold standard." METHODS: We prospectively
      studied 65 patients (54 women and 11 men) who had recurrent varicose veins 1-30
      years (mean, 11 years) after surgical exploration of the groin and ligature of
      the great saphenous vein at its junction with the femoral vein. Duplex scans were
      performed in all patients before surgical reexploration. Sonographic findings
      were compared with surgical findings. RESULTS: Duplex scanning revealed a
      residual stump in 47 patients (72%) and no stump in 15 patients (23%). Thirty
      five (74%) of the 47 cases with a residual stump had reflux on duplex scans, and
      the remaining 12 cases (26%) showed no reflux. Findings in all 62 of these cases
      were confirmed by surgery. In only 3 patients (5%) did duplex scans fail to show
      a residual stump when surgery revealed a small residual stump without reflux.
      CONCLUSIONS: Duplex scanning is the noninvasive diagnostic technique of choice to
      detect any residual stump of the great saphenous vein and to diagnose valve
      failure at the sapheno-femoral venous junction in patients with recurrent
      varicose veins.

PMID- 9783249
TI  - Prenatal sonographic diagnosis of Cantrell's pentalogy with cystic hygroma in the
      first trimester.
AB  - We report 2 cases of Cantrell's pentalogy with cystic hygroma diagnosed in the
      first trimester of pregnancy. Both fetuses had ectopia cordis, omphalocele, a
      sternal defect, and cystic hygroma detected by sonography. Cystic hygroma may be
      another characteristic of Cantrell's pentalogy in the first trimester.

PMID- 9783250
TI  - Bilateral epididymal Candida abscesses: sonographic findings and sonographically
      guided fine-needle aspiration.
AB  - We report the case of a 67-year-old diabetic man who presented 2 months after
      transurethral prostate surgery with impaired consciousness, urinary incontinence,
      and recurrent urinary tract infections that did not respond to antibiotic
      treatment. Sonographic findings suggested abscess formation (enlarged,
      heterogeneous epididymides and a central hypoechoic area in the head of the left
      epididymis). Aspirates obtained from sonographically guided needle biopsy were
      purulent. Staining showed budding yeast forms, and Candida albicans grew in
      culture. Systemic candidiasis was diagnosed. The patient underwent bilateral
      epididymo-orchiectomy, and pathologic analysis of resected specimens showed
      bilateral epididymal necrosis and disseminated abscess formation.

PMID- 9783251
TI  - Plum stones: an unusual cause of ileostomy obstruction demonstrated by
      sonography.
AB  - Bowel obstruction is a common cause of stomal complications of ileostomy. We
      report a case in which sonography revealed 2 well-defined, rounded, hyperechoic
      structures, measuring 1.7 cm in diameter and causing dense acoustic shadowing, in
      the lumen of the bowel of a 3-year-old boy with a permanent end ileostomy.
      Endoscopy showed the structures to be freely mobile plum stones in the fluid
      filled terminal ileum. This case demonstrates the usefulness of sonography in the
      diagnostic workup of patients with ileostomy obstruction.

PMID- 9783252
TI  - Hypoechoic periportal cuffing in acute myeloid leukemia.
AB  - We report a case of hypoechoic periportal cuffing in a patient with acute myeloid
      leukemia. The hypoechoic area encasing the main portal vein and its branches may
      have been caused by transient lymphedema resulting from the blockage of small
      lymph vessels or from direct periportal infiltration by malignant cells. The
      sonographic abnormality disappeared within 2 weeks of the commencement of
      chemotherapy.

PMID- 9783253
TI  - Dynamic contact maps of protein structures.
AB  - The two-dimensional contact map of interresidue distances is a visual analysis
      technique for protein structures. We present two standalone software tools
      designed to be used in combination to increase the versatility of this simple yet
      powerful technique. First, the program Structer calculates contact maps from
      three-dimensional molecular structural data. The contact map matrix can then be
      viewed in the graphical matrix-visualization program Dotter. Instead of using a
      predefined distance cutoff, we exploit Dotter's dynamic rendering control,
      allowing interactive exploration at varying distance cutoffs after calculating
      the matrix once. Structer can use a number of distance measures, can incorporate
      multiple chains in one contact map, and allows masking of user-defined residue
      sets. It works either directly with PDB files, or can use the MMDB network API
      for reading structures.

PMID- 9783254
TI  - Multiple sequence alignment in HTML: colored, possibly hyperlinked, compact
      representations.
AB  - Protein sequence alignments are widely used in protein structure prediction,
      protein engineering, modeling of proteins, etc. This type of representation is
      useful at different stages of scientific activity: looking at previous results,
      working on a research project, and presenting the results. There is a need to
      make it available through a network (intranet or WWW), in a way that allows
      biologists, chemists, and noncomputer specialists to look at the data and carry
      on research--possibly in a collaborative research. Previous methods (text-based,
      Java-based) are reported and their advantages are discussed. We have developed
      two novel approaches to represent the alignments as colored, hyper-linked HTML
      pages. The first method creates an HTML page that uses efficiently the image
      cache mechanism of a WWW browser, thereby allowing the user to browse different
      alignments without waiting for the images to be loaded through the network, but
      only for the first viewed alignment. The generated pages can be browsed with any
      HTML2.0-compliant browser. The second method that we propose uses W3C-CSS1-style
      sheets to render alignments. This new method generates pages that require recent
      browsers to be viewed. We implemented these methods in the Viseur program and
      made a WWW service available that allows a user to convert an MSF alignment file
      in HTML for WWW publishing. The latter service is available at http:@www.lctn.u
      nancy.fr/viseur/services.htm l.

PMID- 9783255
TI  - World Wide Web-based system for the calculation of substituent parameters and
      substituent similarity searches.
AB  - Easy to use, interactive, and platform-independent WWW-based tools are ideal for
      development of chemical applications. By using the newly emerging Web
      technologies such as Java applets and sophisticated scripting, it is possible to
      deliver powerful molecular processing capabilities directly to the desk of
      synthetic organic chemists. In Novartis Crop Protection in Basel, a Web-based
      molecular modelling system has been in use since 1995. In this article two new
      modules of this system are presented: a program for interactive calculation of
      important hydrophobic, electronic, and steric properties of organic substituents,
      and a module for substituent similarity searches enabling the identification of
      bioisosteric functional groups. Various possible applications of calculated
      substituent parameters are also discussed, including automatic design of
      molecules with the desired properties and creation of targeted virtual
      combinatorial libraries.

PMID- 9783256
TI  - Prediction of properties of chiral compounds by molecular topology.
AB  - A common assumption in chemistry is that chiral behavior is associated with 3-D
      geometry. However, chiral information is related to symmetry, which allows the
      topological handling of chiral atoms by weighted graphs and the calculation of
      new descriptors that give a weight to the corresponding entry in the main
      diagonal of the topological matrix. In this study, it is demonstrated that,
      operating in this way, chiral topological indices are obtained that can
      differentiate the pharmacological activity between pairs of enantiomers. The 50%
      inhibitory concentration (IC50) values of the D2 dopamine receptor and the sigma
      receptor for a group of 3-hydroxy phenyl piperidines are specifically predicted.
      Moreover, the sedative character of a group of chiral barbiturates can be
      identified.

PMID- 9783257
TI  - SLASH: a program for analysing the functional groups in molecules.
AB  - The program SLASH, which is designed to enable large numbers of compounds to be
      analysed in terms of the functional groups they contain, is described. The
      usefulness of the groups for analysing the activities of compounds tested in high
      throughput biological screens is investigated. The functional group fragments are
      also studied as a means of determining similarity within groups of compounds.

PMID- 9783258
TI  - The use of VRML in chemical education.
AB  - The Virtual Reality Modelling Language can be used for molecular modelling. The
      language provides some significant advantages in the area of chemical education;
      it can be used to communicate 3D concepts not normally covered by existing
      modelling packages, the data can be distributed to a large number of students
      over the web, and the viewers are free to students. The strengths and weakness of
      VRML in various aspects of molecular modelling are discussed.

PMID- 9783259
TI  - Induction of type 2 cytokines by a staphylococcal enterotoxin superantigen.
AB  - Persistent intramammary infections of dairy cows with Staphylococcus aureus may
      involve immunosuppression mediated by bacterial toxins such as enterotoxins and
      other super-antigens (SAgs). Previously we found that stimulation of bovine PBMC
      with staphylococcal enterotoxin C (SEC) induced a unique phenotype of activated
      CD8+ T cells expressing a newly identified activation molecule, ACT3. In the
      present study we found that SEC induced the expression of interleukin (IL)-4 and
      IL-10 mRNAs, two cytokines associated with type 2 responses. Elevated levels of
      IL-4 and IL-10, observed between day 0 and day 4 of culture, were associated with
      temporary inhibition of proliferative responses of T cells, evidenced by a
      decrease in numbers of CD4+ T cells and a small increase in numbers of CD8+ T
      cells. Vigorous proliferation of T cells occurred between days 4 and 7 of culture
      and with a bias towards CD8+ T cells. Acquisition of the ACT3+ phenotype by CD8+
      T cells was preceded by induction of IL-4 mRNA. Thus, in the bovine system, SAgs
      may hinder protective responses by inducing type 2 cytokines, which interfere
      with immune clearance of many microbial pathogens. The results of the study are
      consistent with the hypothesis that SAgs are involved in immunosuppression, and
      suggest possible immunomodulatory mechanisms.

PMID- 9783260
TI  - Isolation of synaptotagmin as a receptor for types A and E botulinum neurotoxin
      and analysis of their comparative binding using a new microtiter plate assay.
AB  - Clostridium botulinum neurotoxin acts on nerve endings to block acetylcholine
      release. Binding of the neurotoxin to a membrane receptor through its heavy chain
      is the first essential step in its mode of toxin action. Type E botulinum
      neurotoxin (BoNT/E) or type A botulinum neurotoxin (BoNT/A) receptor was purified
      from rat brain synaptosomes employing a neurotoxin affinity column
      chromatography. The protein fraction eluted from the affinity column with 0.5 M
      NaCl contained a 57 kDa protein as a major eluant. Immunoblotting the eluant with
      anti-synaptotagmin antibodies revealed that the 57 kDa protein was synaptotagmin
      I. Rat synaptotagmin I has been suggested as the receptor for BoNT/B (Nishiki et
      al., J. Biol. Chem. 269, 10498-10503, 1994) in rat brain. In this study, binding
      of BoNT/A and BoNT/E to synaptotagmin I was studied by a microtiter plate-based
      method. Binding of synaptotagmin I to BoNT/A coated on the plate was
      competitively reduced upon preincubation of the proteins with BoNT/E, suggesting
      a competitive binding of BoNT/A and BoNT/E to the receptor. Taken together, these
      results suggest that the same receptor protein binds to all three BoNT serotypes
      tested.

PMID- 9783261
TI  - Predictions of secondary structure and solvent accessibility of the light chain
      of the clostridial neurotoxins.
AB  - Predictions were made of the secondary, two-dimensional (2-D) structures and side
      chain solvent accessibilities of the light (L) chains of the clostridial
      neurotoxins (botulinum neurotoxin serotypes A-G and tetanus neurotoxin). An
      artificial neural network was used to make these predictions from a multiple
      alignment of their primary structures and was the approach used in making
      successful predictions for the C-fragments of these neurotoxins (Lebeda et al.,
      J. Prot. Chem., 17:311, 1998). We also exploited the fact that the L-chains are
      Zn-dependent proteases. Although no other metalloproteases were found to be
      sequentially homologous to these neurotoxin L-chains, a sequence clustering
      algorithm showed that several bacterially derived Zn-dependent proteases,
      including thermolysin, were the most similar. A 2-D structure topology map for
      the type A L-chain was constructed by using thermolysin as a design template. As
      in thermolysin, the region containing the Zn-binding sequence motif, which is
      part of the active site in these neurotoxins, was predicted to be minimally
      solvent accessible. On the other hand, the locations of residues with highly
      exposed side chains were predicted to occur in non-periodic structure elements.
      Together, these 2-D structure and solvent accessibility predictions can be used
      to identify important solvent-exposed regions of the L-chain. These regions may
      include sites that interact with residues of the neurotoxin heavy chain, sites
      that bind to vesicle-docking substrates or sites that form antibody epitopes.

PMID- 9783262
TI  - Hemagglutinin binding mediated protection of botulinum neurotoxin from
      proteolysis.
AB  - Type A Clostridium botulinum, the causative agent of the food poisoning botulism
      disease, secretes botulinum neurotoxins along with seven neurotoxin associated
      proteins (NAPs). The function of NAPs has been shown to protect the neurotoxin
      from acidity, heat, and proteolytic attack in the environmental and
      gastrointestinal tract during the toxicogenesis of the botulism disease. One of
      the NAPs, purified from type A botulinum neurotoxin complex, showed
      hemagglutination activity. A direct interaction has been demonstrated between
      purified NAP, a 33-kDa hemagglutinin or Hn-33, and the neurotoxin by using
      Sephadex G-200 column chromatography. Furthermore, Hn-33 has complete resistance
      against proteolytic attack at pH 2.0 as well as at normal physiological pH. We
      have investigated digestion of the neurotoxin in the presence and absence of Hn
      33. The neurotoxin alone has been found to be more susceptible to the enzymatic
      digestion than neurotoxin with Hn-33. The presence of Hn-33 changes the
      proteolytic fragmentation pattern of the neurotoxin. It seems that Hn-33 protects
      the neurotoxin from proteolysis either by structural modification of the
      neurotoxin or by blocking the protease accessible sites of the neurotoxin.

PMID- 9783263
TI  - Characterization of the deoxyribonuclease and ADP-ribosyltransferase activities
      of CRM45, a truncated homologue of diphtheria toxin.
AB  - CRM45 is a mutant form of diphtheria toxin (DTx) that lacks a 17-kDa carboxyl
      terminal segment of the receptor-binding B subunit (DTB). The missing segment is
      a discrete structural domain of DTB that normally rests against the NAD binding
      pocket of the enzymically-active A subunit (DTA). Proteolytic cleavage and
      disulfide bridge reduction in the DTA-DTB linker region of DTx are required for
      optimal ADP-ribosylation of elongation factor 2 (EF-2). Here, we show that
      cleaved and uncleaved preparations of X-ray crystal grade CRM45 both exhibit an
      ADP-ribosyltransferase activity similar to that of cleaved DTx. Crystal-grade
      preparations of CRM45 also display a potent deoxyribonuclease activity. However,
      as observed with DTx, cleavage and reduction of CRM45 are not required for
      expression of this nuclease activity. After SDS-PAGE in a gel that contains DNA
      embedded in the matrix, renaturable Ca++/Mg(++)-dependent nuclease-active bands
      co-migrate with intact CRM45 (45 kDa) as well as with the DTA subunit (24 kDa) of
      CRM45. Because the 45-kDa nuclease-active band is unique to the CRM45 form of
      DTx, it offers direct proof that this activity is intrinsic to the DTA domain of
      DTx and its homologues.

PMID- 9783264
TI  - Membrane-inserted colicin E1 channel domain: a topological survey by fluorescence
      quenching suggests that model membrane thickness affects membrane penetration.
AB  - The topography of the closed-state membrane-associated, colicin E1 channel domain
      was examined using depth-dependent fluorescence quenching to determine the
      membrane location of various single Trp residues introduced into the sequence by
      site-directed mutagenesis. We have extended previous studies (Palmer, L. R., and
      Merrill, A. R. (1994) J. Biol. Chem. 269, 4187-4193) with additional single Trp
      residues in the helix 8/9 region, and with an additional quencher located in the
      polar region of the membrane to detect shallowly located Trp residues. Quenching
      data for seven single Trp mutants examined in the previous study, but without the
      shallow quencher, confirmed the previously reported depths. Mutants containing
      single Trp at residues 355, 460, or 507 were found to be more shallowly located
      than those at 404, 443, 484, or 495. In addition, analysis of fluorescence in the
      presence of the shallow quencher eliminated the possibility that there is a
      predominant population of these residues residing near the membrane-aqueous
      interface. The fluorescence quenching of three new single Trp at residues 478,
      492, or 499 introduced into the channel domain was also evaluated. These residues
      were found at either medium or deep locations in the bilayer. Of special interest
      was the position of the Trp at residue 492 (W492), which is within the loop
      region connecting hydrophobic helices 8 and 9. If helices 8 and 9 were fully
      transmembraneous, then the predicted W492 location would have been shallow.
      Instead the quenching pattern demonstrated W492 to be deeply embedded in the
      lipid bilayer. We also studied the effect of altering bilayer width on protein
      conformation. Membrane width had little effect on most residues, but Trp at
      residues 478 and 507 were located more shallowly in thin bilayers. We also
      examined the effect of bilayer width on the position of Cys 505 labeled with
      bimane, an environmentally sensitive fluorophore. As the membrane width was
      decreased, C505-bimane shifted into a more nonpolar environment, as judged by
      fluorescence emission lambda max and quenching. Models for the conformation of
      helices 8/9 and the effect of membrane width on these helices are considered. We
      conclude that helices 8 and 9 probably do not adopt a fully transmembraneous
      state under the conditions examined in this report.

PMID- 9783265
TI  - Assembly of Clostridium perfringens epsilon-toxin on MDCK cell membrane.
AB  - Clostridium perfringens epsilon-toxin bound to the Madin Darby canine kidney
      (MDCK) cells and aggregated. The complex of the toxin was formed in a dose- and a
      time-dependent manner. The formation of the complex increased with a decrease in
      viable counts of MDCK cells and with increasing K+ release from the cells. The
      inactivated toxin heated at 100 degrees C did not aggregate under the condition.
      In addition, the prototoxin dose-dependently bound to the cells, but did not form
      the complex. Incubation of the toxin with MDCK cell membranes also showed the
      formation of the complex, but that with membrane preparations prepared from Vero
      cells or sheep erythrocytes, which are insensitive for the toxin, showed no
      formation of the complex. Incubation of the toxin with mouse brain homogenates
      resulted in formation of the complex, but that with brain homogenates heated at
      80 degrees C or mouse liver homogenates showed no formation of the complex. These
      observations show that the complex formation of epsilon-toxin is essential for
      toxicity of the toxin.

PMID- 9783266
TI  - Image processing in stereotactic planning: volume visualization and image
      registration.
AB  - Radiation treatment planning (RTP), historically an image-intensive discipline
      and one of the first areas in which three-dimensional (3D) information from
      imaging was clinically applied, has become ever more critically dependent on
      accurate 3D identification of target and non-target organs with the advent of
      conformal radiation therapy, stereotactic radiotherapy, and radiosurgery. In
      addition to the interactive display of wire-frame or shaded surface models of
      anatomical objects, proposed radiation beams, and calculated dose distributions,
      use may also be made of direct visualization of relevant anatomy from image data.
      Although anatomical analysis of dose distributions is an essential component of
      radiation treatment design which requires geometric definition (i.e.,
      segmentation) of all volumes of interest, geometric targeting with optimization
      based on 3D anatomical information is frequently performed as a separate step
      independent of dose calculations. For this early step in the planning process,
      and certainly for diagnostic purposes, visualization without explicit
      segmentation may be a useful additional capability. Additionally, we suggest that
      direct visualization of high contrast targets such as arteriovenous malformations
      (AVM) from computerized tomography (CT) or magnetic resonance (MR) angiography
      may serve as a tool for target volume delineation. Frequently, information from
      multiple modalities or multiple scans of the same modality is important in
      planning a given case. In such instances, image registration may prove useful to
      allow synthesis of information from multiple sources into a single consistent
      coordinate frame. Numerous image registration methods are available, each with
      characteristic strengths and weaknesses.

PMID- 9783267
TI  - Quality assurance in linac-based stereotactic radiosurgery and radiotherapy.
AB  - Stereotactic Radiosurgery demands extraordinary attention to quality assurance
      issues. This is related to the high accuracy needed to perform a successful
      procedure, accuracy demanded by the proximity of the target lesion to neighboring
      fragile and eloquent structures in the head and large doses delivered. The nature
      of the linac-based radiosurgery procedure is that of a series of steps, each
      linked together and requiring quality control, for if one step is faulty the
      final result will be equally faulty. The salient points associated with the
      quality assurance of each step are laid out in this article. Implementation of a
      linac-based radiosurgery program in an institution must be well thought out and
      must be a team effort, involving expertise in medical physics, radiological
      imaging, radiation oncology, and specially trained radiation therapists in order
      to be successful and safe.

PMID- 9783268
TI  - Small photon field dosimetry for stereotactic radiosurgery.
AB  - Performing and assuring the quality of the planning and delivery of stereotactic
      radiosurgery with photon beams requires accurate evaluation of beam parameters,
      usually including output factors, tissue-phantom ratios and off-axis ratios, and
      measurement of actual dose distributions from simulated treatments. For the small
      photon fields used in radiosurgery, these measurements require special equipment
      and techniques, which are described in this review.

PMID- 9783269
TI  - Do we need Monte Carlo treatment planning for linac based radiosurgery? A case
      study.
AB  - The accuracy of conventional empirical and semi-empirical dose calculation
      algorithms for radiation therapy treatment planning is limited. The main problem
      is that these algorithms fail to adequately consider the lateral transport of
      radiation. Most conventional algorithms use measured dose distribution data as
      input. These data induce an added inaccuracy to stereotactic radiosurgery dose
      calculations due to the difficulty of acquiring accurate dosimetric data for very
      small beams; however, since multiple arcs of large solid angles are usually used
      in stereotactic radiosurgery, the errors introduced by conventional dose
      algorithms are quite likely to be diluted. The use of Monte Carlo treatment
      planning for stereotactic radiosurgery has been investigated and described in the
      present paper. The OMEGA Monte Carlo code system is used as the dose engine in an
      in-house developed radiosurgery treatment planning system. The Monte Carlo
      treatment plans are done for two typical clinical cases. In one case, the
      collimator of 20 mm diameter is used and the lesion is located in the peripheral
      part of the brain. In the other case, the collimator diameter is 30 mm and the
      lesion is in the central part of the brain. The resultant dose distributions are
      compared with those calculated with a conventional dose algorithm which is based
      on the standard Tissue Maximum Ratio (TMR)/Off Axis Ratio (OAR) formalism.
      Without the inhomogeneity correction, the conventional algorithm yields accurate
      relative dose distributions for both cases compared with the Monte Carlo
      calculations. The absolute dose at the isocenter may be overestimated by the
      conventional algorithm by 1.5% for the first case and 2.6% for the second case;
      however, using the method of ratio of TMRs for inhomogeneity correction, the
      overestimation can be greatly reduced for both cases. The inclusion of the
      inhomogeneity correction into the conventional dose algorithm does not alter the
      relative dose distributions. Based on the clinical cases studied, it may be
      concluded that the conventional dose algorithm is sufficient for radiosurgery
      treatment planning and the Monte Carlo based radiosurgery treatment planning is
      unwarranted.

PMID- 9783270
TI  - Treatment planning of stereotactic convergent gamma-ray irradiation using Co-60
      sources.
AB  - The basic features of the convergent Co-60 gamma-ray unit, known as Gamma Knife
      and the standard procedures of treatment planning for various cases in general
      have been described in details. The new generation of the rotating gamma system
      and the future clinical applications are briefly mentioned.

PMID- 9783271
TI  - Linac scalpel radiosurgery at the University of Florida.
AB  - Optimal implementation of stereotactic radiosurgery requires multidisciplinary
      input from neurosurgeons, radiation oncologists, and physicists. Clinical
      processes of most importance to the physics staff include stereotactic imaging,
      treatment planning, and radiation delivery. Careful attention to each of these
      details helps to ensure the quality of the overall process. Here we provide a
      practical review of the clinical processes involved in linac scalpel
      radiosurgery. The linac scalpel system is a linear-accelerator-based radiosurgery
      system that was developed at the University of Florida. It has been used at the
      University of Florida to treat more than 1000 patients since 1988. The aim of the
      linac scalpel system is to minimize all possible uncertainties in imaging and
      treatment delivery. Once these errors are minimized, truly conformal treatment
      plans can be generated and delivered with confidence, allowing clinicians to
      focus solely on the patient's problem. By following practical examples of this
      well established system, many pitfalls in the clinical process can be avoided.

PMID- 9783272
TI  - Linac radiosurgery at the Joint Center for Radiation Therapy.
AB  - The Joint Center for Radiation Therapy (JCRT) has treated intra-cranial lesions
      with high-dose single fraction stereotactic radiosurgery (SRS) since 1986 and
      with multi-fraction stereotactic radiotherapy (SRT) since 1992. This paper
      describes the JCRT techniques for treatment planning and delivery for SRS, and to
      a limited extent for SRT. LINAC quality assurance, treatment delivery, and
      patient management for stereotactic radiosurgery and stereotactic radiotherapy
      technique are closely related at the JCRT, although differences exist. An
      historical retrospective of our experience with stereotactic techniques including
      imaging modalities, treatment planning techniques, optimization methods, and
      treatment delivery is presented. Three treatment planning approaches, single
      isocenter, multiple isocenter, and micro-jaw field shaping are used to
      demonstrate the capabilities and technical dosimetric features of each approach.
      The major planning differences and clinical of each technique are described. From
      our experience, lesions less than 3.0 cm in maximum extent are well treated with
      circular fields using either a single or multiple isocenter configuration.
      Lesions greater than 3.0 cm in maximum extent usually benefit from field shaping
      using the micro-jaws. For these large lesions, the shaped field approach
      typically improves the dose homogeneity as well as reduces the amount of healthy
      brain irradiated. Our physicians choose between the three techniques to meet the
      desired clinical outcome the patient's situation requires.

PMID- 9783273
TI  - The radiobiology of radiosurgery and stereotactic radiotherapy.
AB  - Radiation therapy has evolved into a complex amalgamation of treatment techniques
      that differ significantly according to the way the radiation is delivered to the
      patient and coincidentally according to the biologic effects that are observed
      with each technique. Although there are concepts within radiobiology that unify
      the field, it is not apparent that the biologic effects with one methodology of
      treatment resemble those of another. Radiosurgery, although initially developed
      in the 1950s, has become more commonly used in recent years. This treatment
      involves high-dose, single-fraction treatments with sharp dose gradients to small
      volumes of tissue. This contrasts with conventional external-beam radiotherapy
      which involves small-dose, multiple-fraction, broad-dose-gradient treatment to
      relatively large volumes of tissue. Stereotactic radiotherapy generally delivers
      small-dose, multiple-fraction treatments to small or intermediate volumes of
      tissue with a sharp dose gradient compared with conventional external-beam
      treatment. A discussion of these technique differences with reference to the
      radiobiologic implications may help elucidate the potential utility of the
      techniques in clinical radiotherapy.

PMID- 9783274
TI  - Fractionated stereotactic radiotherapy: rationale and methods.
AB  - Stereotactic radiosurgery (SRS) has become a widely accepted technique for the
      treatment intracranial neoplasms. Combined with modern imaging modalities, SRS
      has established its efficacy in a variety of indications. From the outset,
      however, it was recognized that the delivery of a single large dose of radiation
      was essentially "bad biology made better by good physics." To achieve the
      accuracy required to compensate for this biological shortcoming, the application
      of SRS has required that a neurosurgical head frame of some sort be rigidly
      attached to the patients head. Historically, this prerequisite has, primarily for
      practical reasons, precluded the delivery of multiple fractions over multiple
      days. With recent improvements in immobilization and repeat fixation, the good
      biology of fractionated delivery has been realized. This technique, which has
      come to be known as stereotactic radiotherapy (SRT), has significantly expanded
      the efficacy of the technique through the use of accurate physical targeting
      coupled with the basic radiobiological principles gleaned from decades of
      clinical experience.

PMID- 9783275
TI  - Optic-guided stereotactic radiotherapy.
AB  - Stereotactic localization provides a powerful referencing system for radiation
      planning and treatment delivery. Although the standard approach of applying a
      rigid reference frame has been accepted for single-fraction therapy, a new,
      noninvasive approach is needed for fractionated therapy. The use of optical
      tracking allows a patient's position to be monitored in real time with a truly
      touch-free system. Our optical system provides high precision and accuracy for
      repeat fixation and can be applied to a wide spectrum of patients. With this
      system, a stereotactic radiation treatment can be delivered in the same length of
      time as a routine fractionated radiation treatment.

PMID- 9783276
TI  - Beam shaping for SRT/SRS.
AB  - Field shaping for stereotactic radiosurgery and stereotactic radiotherapy has
      evolved from static field shaping techniques applied to static or arc fields and
      now includes dynamic field shaping definition which can be dynamically modified
      during the arc. This allows greater conformation of dose to the target volume
      while minimizing dose to surrounding normal tissue. This results in treatment to
      a single isocenter, which simplifies the treatment planning and dose delivery,
      thereby minimizing treatment time and improving patient comfort and satisfaction
      during the treatment. A number of optimization techniques remain to be
      investigated.

PMID- 9783277
TI  - Intensity modulated conformal therapy for intracranial lesions.
AB  - The Peacock planning and delivery system was used to create treatment plans and
      deliver these plans to patients. The system involves an arc therapy delivery of
      small (2 cm long) slices of radiation combined with indexing of the couch to
      achieve target coverage. Two clinical examples are shown to demonstrate the
      system's capability and evaluate the resources required to produce and deliver
      the plans. One plan is an optic sheath meningioma and the other is a
      craniopharyngioma that surrounded the optic chiasm. The optic sheath meningioma
      was treated to 50 Gy in 25 fractions. The treatment involved delivery of two
      arcs. The total time to set up the patient and deliver the treatment was less
      than 15 min. Planning and plan validation after computed tomography required
      approximately 3 days. The patient had 100% restoration of her field of vision and
      is stable 3 years post therapy. The second patient is a 9-year-old who had a
      craniopharyngioma which surrounded the optic chiasm. The tumor was treated to
      50.4 Gy in 28 fractions and the dose to the optic chiasm was limited to 45 Gy.
      The treatment required three arcs and total treatment time was less than 20 min.
      The patient is stable 15 months post therapy. The system is able to create and
      deliver radiation patterns that are unique. These plans can be created and
      delivered in times that rival conventional forward planning conformal
      radiotherapy systems that cannot produce or conveniently deliver such plans.

PMID- 9783278
TI  - A code of ethics for the medical dosimetrist--the American Association of Medical
      Dosimetrists experience.
AB  - The Committee on Protocol and Ethics of the American Association of Medical
      Dosimetrists (AAMD) has developed a Code of Ethics for a radiation oncology
      society of medical dosimetrists. The purpose of the code of ethics is fourfold:
      (1) Establish an ideal of professional conduct specific to the medical dosimetry
      profession; (2) Develop a statement of the moral values and commitment of the
      AAMD; (3) Recognize professional relationships and obligations; and (4) Define
      goals to which the medical dosimetrist should aspire. The Code of Ethics was
      adopted as AAMD policy in October 1995.

PMID- 9783279
TI  - Masters of ophthalmic plastic and reconstructive surgery: Rocko Michael
      Fasanella, a reminiscence. The Archives Committee of the American Society of
      Ophthalmic Plastic and Reconstructive Surgery.

PMID- 9783280
TI  - Blepharospasm: past, present, and future.
AB  - To investigate causes, associations, and results of treatment with blepharospasm,
      1,653 patients were evaluated by extensive questionnaires to study blepharospasm
      and long-term results of treatment with the full myectomy operation, botulinum-A
      toxin, drug therapy, and help from the Benign Essential Blepharospasm Research
      Foundation (BEBRF). The percent of patients improved by the BEBRF was 90%, full
      myectomy 88%, botulinum-A toxin 86%, and drug therapy 43%. The patient acceptance
      rate for the BEBRF was 96%, full myectomy 82%, botulinum-A toxin 95%, and drug
      therapy 57%. Blepharospasm is multifactorial in origin and manifestation. A
      vicious cycle and defective circuit theory to explain in origin and direct
      treatment rather than a defective specific locus is presented. All four forms of
      therapy evaluated are useful and must be tailored to the patient's needs. Mattie
      Lou Koster and the BEBRF have helped blepharospasm sufferers more than any other
      modality, and all patients should be informed of this support group. The full
      myectomy is reserved for botulinum-A toxin failures, and the limited myectomy is
      an excellent adjunct to botulinum-A toxin.

PMID- 9783281
TI  - Postimplantation density changes in coralline hydroxyapatite orbital implants.
AB  - The purpose of our study was to determine serial mineral density changes in
      coralline hydroxyapatite orbital implants after implantation into the human
      socket. Prospective analysis by quantitative computed tomography determined the
      mineral density of hydroxyapatite orbital implants in five patients before and at
      two time intervals after implantation. Mineral density of the spheres increased
      an average of 135% after implantation (3-8 months) from preoperative
      measurements. The density continued to rise an average of 5% (range, -9%-16%) at
      the second postoperative period (22-39 months). Average follow-up was 30 months.
      The increased density in the nonevisceration patients was noted in the regions of
      the scleral windows and the exposed posterior implant where the cornea had been
      removed from the scleral wrap. The mineral density of hydroxyapatite spheres
      markedly increases after implantation. Approximately 2 to 3 years later, the
      densities continue to increase slightly in enucleation and secondary implant
      cases. An evisceration implant was the only implant to lose density. This study
      shows no decrease in the mineral density of orbital coralline hydroxyapatite
      enucleation implants, suggesting a lack of implant mineral resorption.

PMID- 9783282
TI  - High-resolution magnetic resonance imaging of the orbital connective tissue
      system.
AB  - A complex system of connective-tissue septa within the orbit has previously been
      described in serial histologic sections. The present study describes the anatomy
      of the orbital connective tissue system on high-resolution magnetic resonance
      (MR) images in vivo. Five volunteers aged 26 to 35 year underwent magnetic
      resonance imaging of the orbit on a 1 Tesla unit (Impact, Siemens, Germany). T1
      weighted coronal images were obtained using a surface coil. Anatomical structures
      on the MR images were identified by comparison with corresponding histologic
      sections. On MR images of the anterior orbit, the levator aponeurosis, Lockwood
      ligament, transverse intermuscular ligament, common sheath, check ligaments,
      Tenon capsule, intermuscular septa, and palpebral ligaments can be seen. In the
      mid- and posterior orbit, the intermuscular orbital septa, especially the
      superolateral septum, the superior ophthalmic vein hammock, and septa of the
      radial connective tissue system are visualized. High-resolution magnetic
      resonance imaging is capable of delineating the major septa of the orbital
      connective tissue system.

PMID- 9783283
TI  - Eyeball position in Graves orbitopathy and its significance for eyelid surgery.
AB  - The goal of this article is to investigate the effect of Graves orbitopathy and
      orbital decompression on the position of the eyeball, and to relate this to a
      straight upper eyelid contour, observed in several patients after correction of
      upper eyelid retraction. The positions of the pupil center and the upper and
      lower eyelid margin were measured in relation to a reference line through the
      medial canthi, on slides obtained from 120 eyelids before and after correction of
      upper eyelid retraction, and on similar slides obtained from 90 control eyelids.
      In control subjects, the distance between the reference line and the pupil center
      was, on average, 4.5 mm (SD 1.2 mm). In decompressed patients, the pupil center
      was, on average, 2.2 mm lower (SD 1.3 mm), and in nondecompressed patients it
      was, on average 1.0 mm lower (SD 1.2 mm). A relatively straight upper eyelid
      contour after otherwise satisfactory correction of upper eyelid retraction was
      observed in 14 eyelids of 8 patients. All cases occurred in decompressed patients
      with a distance between the pupil center and the reference line of 2 mm or less.
      No significant difference was found in the position of the lateral canthal angle
      between the three groups. Many patients with Graves orbitopathy show a downward
      shift of the pupil center in relation to a reference line through the medial
      canthi. This is partially caused by orbital decompression, but also by other
      factors discussed by the authors. If the distance between this reference line and
      the pupil center is 2 mm or less, otherwise satisfactory correction of upper
      eyelid retraction may cause visible straightening of the upper eyelid contour.

PMID- 9783284
TI  - Deep transorbital approach to the apex and cavernous sinus.
AB  - Tumors of the orbital apex are difficult to approach through a standard lateral
      orbitotomy exposure. The transcranial approach has been described, but it
      requires an open craniotomy as well as dissection through the annulus of Zinn in
      its tight superior segment to reach intraconal and inferior lateral tumors. It is
      well recognized that the transcranial approach is optimal only for tumors of the
      superomedial orbital apex. Our study demonstrates that by enlarging the bony
      incision of a classic lateral orbitotomy to include a generous marginotomy and
      removing the deep sphenoid wing up to the superior orbital fissure, good exposure
      of the lateral orbital apex can be obtained. Tumors of the apex, including those
      that extend slightly into the cavernous sinus, can be removed from the cranial
      nerves and extraocular muscle origins in en face fashion, providing optimal
      ability to identify the delicate neurovascular structures of the orbital apex and
      avoid damage to them. The operating microscope is extremely useful for bony and
      soft tissue dissection. We report four benign tumors of the orbital apex removed
      using this approach. Two tumors encroached slightly into the cavernous sinus.
      Three of four patients were told that they had inoperable tumors. By use of the
      deep orbital apex approach described, all four tumors were successfully exposed
      and removed. Visual and motor function was unchanged or improved in all four
      patients, with the exception of one tumor that incorporated the inferior division
      of the third cranial nerve; in that patient, the transected nerve was anastomosed
      microscopically, and partial return of function was noted. The transorbital
      ophthalmic approach to tumors of the inferolateral orbital apex has significant
      potential advantages in comparison with a frontal craniotomy approach.

PMID- 9783285
TI  - Ruptured globe during orbital decompression surgery.
AB  - A 74-year-old patient sought treatment for visual obscuration and clinically had
      signs of Graves orbitopathy. Past medical history was unremarkable except for the
      use of antihypertensive medication. During the hospital admission, a fluorescent
      treponemal antibody absorption test was reactive, indicating infection with
      syphilis at some time in the past. Visual deterioration despite oral
      corticosteroid therapy prompted orbital decompression. At the time of surgery,
      she sustained a globe rupture. Presumably, syphilitic scleritis was responsible,
      in part, for scleral thinning and weakening, predisposing her to this
      complication. To the authors' knowledge, globe rupture has not been previously
      reported during orbital decompression.

PMID- 9783286
TI  - Multiple orbital intraosseous hemangiomas.
AB  - The case of a 36-year-old healthy, asymptomatic man who was monitored for a
      slowly growing subcutaneous mass under his right inferior orbital rim for more
      than ten years is presented. The mass was hard, immobile, and nontender. Computed
      tomography (CT) documented a lytic lesion at the frontal process of the right
      maxilla. Four years later, magnetic resonance imaging (MRI) of the orbits
      revealed distinct lesions in the right zygoma, maxillary, and greater wing of the
      sphenoid bones. These lesions were hypointense with respect to orbital fat on T1
      weighted images and hyperintense on T2-weighted series. There was moderate
      enhancement after contrast agent administration. These findings combined with the
      clinical features of the patient were suggestive of presumed multiple orbital
      intraosseous hemangiomas. Differential diagnosis between other osseous tumors of
      the orbit can be reasonably made based on imaging characteristics.

PMID- 9783287
TI  - Tarsal kinking after Hughes flap.
AB  - A retrospective review of 45 patients undergoing the Hughes tarsoconjuctival flap
      procedure for lower eyelid reconstruction detected three individuals who
      developed kinking of the tarsus and upper eyelid margin. This unusual
      complication became apparent at the time of flap division. A horizontal band of
      fibrosis at the superior border of the remaining upper eyelid tarsus was
      appreciated in two of the patients. Excision of the fibrotic tissue resulted in
      an immediate improvement of the deformity.

PMID- 9783288
TI  - Multiple aesthetic unit flaps for medial canthal reconstruction.
AB  - The medial canthal region includes several individual aesthetic units that differ
      in skin quality and thickness, contour, and associated landmarks. Basal cell
      carcinomas commonly involve the medial canthal region and extend without
      respecting the boundaries between units. Reconstruction of tumor-free defects is
      often complicated by web formation across the medial canthal concavity. To avoid
      this complication, we evaluate each defect according to the anatomic units
      involved and develop individual flaps from each component area, anchoring each
      flap to the medial canthal tendon or associated deep fibrous tissue. This system
      has been used in 58 cases with excellent results. It allows flexibility for
      reconstructing the many diverse defects that oculoplastic surgeons encounter and
      helps to minimize postoperative deformity.

PMID- 9783289
TI  - The modified rhomboid transposition flap in periocular reconstruction.
AB  - The traditional rhomboid transposition flap has been widely used in
      reconstructive surgery. The authors have modified the original technique by
      eliminating the creation of the rhomboid defect and by directly transposing the
      flap into the original postexcisional defect. These changes allow maximum
      flexibility in flap design and minimize normal tissue loss. The authors
      retrospectively reviewed the charts of patients who underwent periocular
      reconstruction with flaps from 1990 through 1995. The authors selected those
      patients in whom the modified rhomboid flap was used. Functional and cosmetic
      results and complications were reviewed. Two hundred thirty-two patients were
      identified in whom 242 flaps were performed. The modified rhomboid flap was used
      in 101 patients (41.7%). Complications occurred in 23 patients (23%), 19 of whom
      (19%) were treated medically and four of whom (4%) required an additional
      surgical procedure. Cosmetic and functional results were classified as very good
      or excellent in 96 patients (96%). The use of a modified rhomboid flap in the
      reconstruction of the periocular area offers ample versatility in flap design and
      minimal normal tissue loss. Functional and cosmetic results are satisfactory in
      the vast majority of cases.

PMID- 9783290
TI  - Surgical management of lower-lid basal cell carcinoma involving the medial
      canthus: a modification of the Mustarde cheek rotation flap.
AB  - The Mustarde cheek rotation flap has proved to be an extremely successful and
      reliable technique for repairing large defects of the lower lid. However, when a
      stump of normal, lash-bearing lid margin remains on the advancing edge of the
      flap, it does not seem appropriate to insert it into a defect that extends more
      medially than the position of the lower punctum. The lid margin must either be
      sacrificed or tissue brought in from the medial side to meet it. To resolve this
      problem, we have devised a modification, which involves utilizing the triangle of
      tissue lying below the defect to fill the gap medial to the position of the
      punctum. The maneuver has proved successful and has now been used on two
      occasions with satisfactory cosmetic and functional results. In this original
      descriptions of the cheek rotation flap, Mustarde sacrificed the triangle of skin
      below the excision defect. However, if a triangular portion is saved, based on
      the upper part of the advancing edge of the flap, this may be used to fill a
      medial defect, obviating the need to import tissue from elsewhere.

PMID- 9783291
TI  - Liposarcoma of the orbit: a management challenge.
AB  - A previously healthy 35-year-old man experiencing slowly progressive, painless
      proptosis of the right eye. Visual function was normal, but supraduction was
      limited. Computed tomography revealed a superior, extraconal orbital mass.
      Subtotal excision was performed, and a diagnosis of liposarcoma was rendered only
      with expert analysis. Despite subsequent orbital exenteration and postoperative
      radiation, a local recurrence developed 5 years later. The clinical features that
      predict recurrence, and management options that may promote longevity, are
      discussed.

PMID- 9783292
TI  - A caruncular dermoid with contiguous eyelid involvement: embryologic
      implications.
AB  - An 11-year-old girl with a mass arising from the caruncle and the upper eyelid
      was examined for spontaneous epibulbar bleeding. Excision of the lesion involved
      reconstruction of the proximal nasolacrimal system, lid margin, and conjunctiva.
      The histopathologic diagnosis was consistent with a dermoid of the caruncle. This
      case is notable not only for a dermoid accompanied by epibulbar bleeding but for
      its caruncular origin and attachment to the upper eyelid. This case suggests that
      the caruncle and the upper eyelid arise from similar embryologic structures.

PMID- 9783293
TI  - Temperament and child dental fear.
AB  - PURPOSE: The relationship between dental fear and temperament in children was
      investigated in 124 Swedish children aged 5-7 and 10-12 years. They represented
      dentally fearful (65) and not fearful (81) children, and were drawn from a larger
      population-based patient pod. The aims of the investigation were to study the
      relationships between temperament on one hand, and dental fear and dental
      behavior-management problems on the other hand. METHODS: Dental fear was measured
      by the Dental Subscale of Children's Fear Survey Schedule (CFSS-DS) and the
      Children's Dental Fear Picture test (CDFP), while the Emotionality, Activity,
      Sociability (EAS) Temperamental Survey was used to assess four aspects of
      temperament: negative emotionality, shyness, sociability, and activity. RESULTS:
      Using Student's t test, children with dental fear had statistically significantly
      higher scores on shyness compared with normative data on EAS from Sweden. When
      fearful children were compared with the others in the study group by the use of
      Student's t test, children with dental fear scored statistically significantly
      higher on both shyness and negative emotionality. CONCLUSION: Thus, children
      expressing shyness and/or tendencies of negative emotionality should be
      considered patients at risk for developing dental fear problems.

PMID- 9783294
TI  - Investigation of the possible associations between fluorosis, fluoride exposure,
      and childhood behavior problems.
AB  - PURPOSE: This study investigated the potential association between fluoride
      exposure and behavior problems in children, as well as the prevalence of and risk
      factors for fluorosis. METHODS: Children between the ages of 7 and 1 years (N =
      197) were included in the study and were examined for dental fluorosis using the
      Modified Dean's Index. Parents of subjects completed and returned three
      questionnaires which investigated their children's history of exposures to
      fluoride, social and medical backgrounds, and behavior using the Child Behavior
      Checklist (CBCL). RESULTS: Sixty-nine percent of the study participants
      demonstrated fluorosis with very mild fluorosis being the most common (39%),
      while 13% demonstrated moderate to severe fluorosis. Using a summation of the
      Modified Dean's index (Sum of 8), we divided the children into high fluorosis
      (HF) and low fluorosis (LF) groups. These groups were compared to each other with
      respect to fluoride exposures and behavior. CONCLUSION: Although there was no
      association between the fluoride exposures in aggregate and fluorosis, there was
      a significant association between supplemental fluoride exposure from ages 0-3
      years and fluorosis. There was no association between behavior problems and
      dental fluorosis in this population.

PMID- 9783295
TI  - The effects of nitrous oxide on pediatric dental patients sedated with chloral
      hydrate and hydroxyzine.
AB  - PURPOSE: The purpose of this prospective, double-blind, crossover study was to
      evaluate the effect of 50% nitrous oxide (N2O) compared to oxygen (O2) alone on
      behavioral and physiologic parameters when a standard regimen of chloral hydrate
      (CH) (50 mg/kg) and hydroxyzine (2 mg/kg) was administered to young children for
      dental procedures. METHODS: Twenty children (mean age 42 +/- 7.3 months) were
      sedated, each for two appointments. At one appointment they received 100% O2 and
      at the other 50% N2O, the order randomized across patients. Physiologic
      parameters measured were heart and respiratory rate, systolic and diastolic blood
      pressure, oxygen saturation, and expired carbon dioxide. Behavior was rated using
      the Ohio State University Behavior Rating Scale. Physiologic and behavioral
      parameters were measured at eight defined procedural events. RESULTS: Results
      indicated differences as a function of inhalation agent were seen for crying,
      quiet, and struggling, but not for any physiologic parameters. Significant
      differences across procedures were found for systolic and diastolic blood
      pressure and for all behaviors (crying, movement, quiet, and struggling).
      CONCLUSIONS: Compared to O2, N2O significantly modifies some behaviors but not
      physiologic parameters in sedated children. However, certain dental procedures
      did significantly modify some physiologic parameters and all behaviors.

PMID- 9783297
TI  - Adaptation of Class II Vitremer restorations with and without primer: a
      morphometric study.
AB  - PURPOSE: The aim of this study was to assess the adaptation of Vitremer with and
      without primer and compare to that of Z100 with Scotchbond Multi-Purpose.
      METHODS: Fifty-seven Class II cavities were prepared in 32 extracted or
      exfoliated primary molars. The cavities were randomly assigned to one of three
      groups and restored as follows: group A, Vitremer with primer (20 preps); group
      B, Vitremer without primer (19 preps); and group C, Z100 with Scotchbond Multi
      Purpose (18 preps). The restored teeth were thermocycled, embedded in acrylic
      resin, and sectioned. At least three 1-mm thick sections were obtained from each
      restoration. Adaptation of the materials was assessed by computerized
      quantitative morphometry using an image analysis system. In addition to the
      margin, the entire contact length between the tooth and the restorative material
      was measured. Voids were recorded separately for the base and cavity margins, and
      the percentage of defected length was calculated. At least three sections of each
      restoration were assessed. The section with the worst results was selected as the
      representative of the restoration. RESULTS: Margin defects were present in 14% of
      all the restorations, equally distributed between the three groups (A, 10%; B,
      16%; C, 17%). A significant difference was found between groups B and C when the
      percentage of defects in the base was assessed. CONCLUSIONS: Vitremer without
      primer presented considerably fewer voids when compared with Z100/Scotchbond
      Multi-Purpose. Although no difference in margin defects could be observed between
      the three groups a better adaptation to the cavity base was seen in the Vitremer
      restorations without primer. This finding might be of clinical importance and
      should be tested in other in-vitro and in-vivo studies.

PMID- 9783296
TI  - Enamel bond strengths of "one-bottle" adhesives.
AB  - PURPOSE: Several "one-bottle" dental adhesives recently have been introduced.
      These contain hydrophilic resin monomers that should readily wet tooth surfaces.
      Most also contain solvents that could increase enamel bond strengths by driving
      out residual moisture from enamel and increasing resin penetration. The purpose
      of this study was to evaluate bond strengths obtained by six one-bottle bonding
      agents and one conventional unfilled resin (control). METHODS: Seventy bovine
      teeth were randomly assigned to seven groups of 10. Enamel was etched for 15 s
      with 35% phosphoric acid. Following application of the adhesive, composite resin
      was bonded using a gelatin capsule technique. Shear bond strengths to enamel were
      determined. RESULTS: Mean bond strengths ranged from 14.2 MPa for Syntac Single
      Component to 27.8 MPa for Single Bond. The mean for Syntac Single-Component was
      significantly less than that of all other systems tested. CONCLUSION: The results
      of this study indicate that one-bottle bonding agents, with the exception of the
      Syntac material, provide enamel bond strengths at least equal to that of a
      conventional unfilled resin.

PMID- 9783298
TI  - The longevity of space maintainers: a retrospective study.
AB  - METHODS: This retrospective study investigated the longevity of 301 space
      maintainers fitted in 141 patients aged 3.4-22.1 years in the Department of
      Pediatric Dentistry at Leeds Dental Institute between 1991 and 1995. RESULTS:
      Failure occurred in 190 space maintainers (63%), of which 36% were due to cement
      loss, 24% breakage, 10% design problems, and 9% were lost. Using the life table
      method, the median survival time (MST) for space maintainers was found to be 7
      months. Band and loop (B&L) appliances had the highest MST of 13 months, while
      the lower lingual holding arch (LLHA) had the lowest of 4 months. Unilateral
      space maintainers survived longer than bilateral space maintainers (MST of 13
      months vs. 5 months). Left B&Ls had a MST of 16 months, compared to only 4 months
      for right B&Ls, Gender, age, arch in which the appliance was placed, the operator
      planning it, fixed vs. removable, and adequacy of pretreatment assessment did not
      have a significant effect on survival time.

PMID- 9783299
TI  - Effect of restorative treatment on mutans streptococci and IgA antibodies.
AB  - PURPOSE: Streptococcus mutans has been implicated as the major causative agent of
      dental caries. Although restorative treatment for caries is thought to
      temporarily eliminate the carious challenge, there are few reports of alterations
      in salivary mutans streptococci (MS) numbers and no reports of changes in
      salivary IgA antibody to S. mutans following restorative treatment. METHODS: This
      study investigated the effects of treatment in 12 caries-active children.
      RESULTS: Numbers of MS decreased slightly from pre- to postrestoration levels in
      six subjects and increased in five subjects. However, there were no significant
      differences in pre-to postrestoration numbers of total oral streptococci, MS, the
      percentage of MS/total oral streptococci, salivary IgA antibody levels to S.
      mutans, or correlations between bacterial counts and IgA antibody levels.
      CONCLUSIONS: These results indicate that successful restorative treatment does
      not alter mutans streptococcal numbers and suggest the need for more effective
      methods for reducing the cariogenic challenge.

PMID- 9783300
TI  - Pattern of permanent teeth present in individuals with ectodermal dysplasia and
      severe hypodontia suggests treatment with dental implants.
AB  - PURPOSE: The objective of this study was to assess the pattern of permanent teeth
      present in a self-selected sample of 17 female and 35 male patients with
      ectodermal dysplasia presenting for treatment with dental implants. METHODS: Mean
      age of sample: 18.7 years, age range: 5.9 to 60.9 years. Panoramic radiographs
      were examined independently by two investigators to determine the permanent teeth
      present. None of the sample reported extractions of permanent teeth prior to
      presenting for implants. RESULTS: Permanent teeth most likely to be present,
      reported as a percentage of the patient sample with that tooth, were: maxillary
      central incisors (42%), maxillary first molars (41%), mandibular first molars
      (39%), maxillary canines (22%), mandibular second molars (17%), maxillary second
      premolars (15%), and mandibular premolars (12%). Comparing dentition by
      quadrants, mandibular anterior teeth (canines and incisors) were least likely to
      be present. CONCLUSIONS: Results support previous findings that the maxillary
      central incisors, maxillary first molars, mandibular first molars, and maxillary
      canines are the most conserved teeth in hypodontia. Successful use of
      osseointegrated implants in the anterior mandibles of most of these patients
      suggests that habilitation of the mandible with dental implant-supported
      prostheses is a reasonable option.

PMID- 9783302
TI  - Factors affecting the mobility of pediatric dentistry faculty.
AB  - PURPOSE: A questionnaire was used to develop a profile of current pediatric
      dentistry faculty to determine whether current faculty would consider relocating
      to accept another position in academia, and to identify what factors are most
      important to current full-time faculty when considering another faculty position.
      RESULTS: Responding males had a significantly higher mean age (49.3 years) than
      the females (39.3 years). A significantly greater proportion of women (87%) than
      men (66%) reported that they were prepared to move if offered an improved career
      opportunity. Both women and men ranked an improved opportunity for professional
      growth followed by salary increase as the highest rated factors in considering
      relocation. There was no statistical difference between women and men at the
      assistant professor level relative to the importance of academic promotion
      opportunity. However, women at the associate professor level ranked an
      opportunity for academic promotion statistically higher than did men.

PMID- 9783301
TI  - The dental status of asthmatic British school children.
AB  - PURPOSE: This study was performed to determine the prevalence of dental disease
      in British school children with asthma. METHODS: A convenience sample of 100
      asthmatic children (aged 4-16 years) was examined for dental caries, periodontal
      condition, and tooth surface loss. School children, equated for age, sex, race,
      and socioeconomic status were chosen for comparison. Children were divided into
      two age ranges; 4-10 and 11-16 years. A significant difference was found in DMFT
      (0.96 vs. 0.31) and DMFS (1.37 vs. 0.37) between the 4-10-year-old asthmatic
      children compared with healthy control children. RESULTS: In the 11-16-year age
      range, the asthmatic children had a DMFT and DMFS of 2.48 and 3.39 compared with
      the control children who had a DMFT and DMFS of 1.11 and 1.97 respectively.
      Asthmatic children had significantly more plaque, gingivitis, and calculus
      compared with the control group. There was a significant difference in the
      severity and number of teeth affected by tooth surface loss affecting labial
      surfaces of the anterior teeth and occlusal surfaces of the posterior teeth of
      asthmatic children. CONCLUSIONS: It was concluded that asthmatic children have
      more decay affecting their permanent teeth, poorer periodontal status, and more
      tooth surface loss than healthy controls.

PMID- 9783303
TI  - Pediatric oncology in Brazil.
AB  - Brazil is a country with many contrasts. This can help the understanding of
      environmental factors influencing the incidence of different cancers. The
      standard treatment and results achieved in certain areas of the country are not
      encountered in others. The establishment of national cooperative groups has
      helped the improvement. The subspecialty has been recognized and training
      programs are available. Many scientific achievements have been developed and are
      described.

PMID- 9783304
TI  - Pediatric hematology and oncology in Children's Hospital of Nancy, France.
      Contribution to the organization of clinical oncology.

PMID- 9783305
TI  - Ongoing assessment of nutritional status in children with malignant disease.
AB  - The nutritional status of a child on cancer therapy influences both tolerance of
      and response to treatment. However, it is difficult to assess nutritional status
      on a daily basis because an accurate quantitation of the calorie intake is
      difficult. Anthropometric and biochemical parameters are prone to error and often
      reflect past rather than current nutritional status. In practice, a subjective
      clinical assessment is usually relied upon. This study objectively appraises the
      value of such an assessment. Based on clinical symptoms that alter oral intake
      and absorption of food, a scoring system was designed to assess nutritional
      status on a day to day basis. A symptom score (SS) of 10 implied "normality"; 0
      indicated maximum debility. Over a 2-year period 511 daily scores were recorded
      in 30 patients aged 0.7-17.5 years. Patients were studied at presentation and
      during treatment for acute lymphoblastic leukemia (ALL, n = 14; solid tumors
      receiving megatherapy with autologous bone marrow rescue (ABMR, n = 8), and
      chemotherapy for different tumors (miscellaneous, n = 8). The SS was compared
      with other nutritional parameters, including sequential anthropometric indices,
      serum albumin, insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP
      3), and whole-body protein turnover (WBPT) using [1-(13) C]leucine. The mean SS
      was reduced at diagnosis for all leukemic patients (median score = 8), improved
      during first remission (p < 0.002), fell to a minimum during febrile neutropenia
      (p = 0.0009), and improved with clinical and hematological recovery (p = 0.0009).
      A reduction in SS was related to fever (p < 0.001) and a fall in neutrophil count
      (p < 0.001). There was no correlation with anthropometric indices or IGF-I and
      IGFBP-3 levels. Paired WBPT studies in 9 patients showed that SS correlated well
      with protein breakdown (p = 0.026). The results suggest that the ongoing
      nutritional status of children with malignancy undergoing chemotherapy is best
      assessed using simple clinical parameters.

PMID- 9783306
TI  - Fever and neutropenia in children with cancer in one pediatric hospital in
      Argentina.
AB  - The authors retrospectively analyzed 863 episodes of neutropenia and fever in 635
      children with cancer or hematological disease hospitalized between October 1988
      and November 1994. The most frequent underlying diseases were solid tumors (45%)
      and acute lymphoblastic leukemia (29%). Clinical site of infection could be
      determined in 454 (53%) episodes. Bacteremia was documented in 114 (13%) cases.
      Gram-positive cocci were the microorganisms most frequently isolated (47% of the
      cases). Noninfectious complications could be determined in 140 (16%) episodes,
      and were mainly severe bleeding and metabolic impairment. The episodes were
      divided in two groups for comparative evaluation: group A, 404 episodes, study
      period 1988-1991, and group B, 459 episodes, 1992-1994. According to the results,
      more patients in group A than group B were younger than 1 year old and had
      profound neutropenia; fewer patients in group A than group B had an endovascular
      catheter, a higher frequency of manifest clinical site of infection at admission,
      and a prevalence of isolation of gram-negative bacilli. A higher percentage of
      patients in group B had neutropenia of more than 14 days, gram-positive cocci in
      culture, and lower mortality. Multivariate analysis by logistic regression in 340
      patients revealed that the presence of a severe noninfectious complication,
      severe neutropenia, and positive blood culture correlated with high mortality
      rate (p < or = 0.001).

PMID- 9783307
TI  - Role of rHuEpo on blood transfusions in preterm infants after the fifteenth day
      of life.
AB  - The specific aim of the study was to assess the safety and efficacy of
      recombinant human erythropoietin (rHuEpo) in reducing the need for blood
      transfusions in preterm infants after the 15th day of life. Between 1 October
      1994 and 1 October 1995, 107 preterm infants, gestational age < or = 34 weeks,
      were admitted to the Neonatal Intensive Care Unit and received rHuEpo
      subcutaneously, 900 U/kg week-1, 3 times weekly, supplemented with iron and
      vitamin E. Treatment was started at 8 days of life and lasted from a minimum of 6
      weeks to a maximum of 3 months. A total of 116 preterm infants of the same
      gestational age, admitted to the Neonatal Intensive Care Unit from 1 January 1992
      to 31 December 1992, served as controls. Entry criteria were gestational age < or
      = 34 weeks and no major congenital malformation. There were no differences in
      routine care between the two groups. Hematological measurements and transfusion
      requirements were followed during therapy. The infants were divided into two
      groups according to birth weight (< 1500 g and > or = 1500 g), and for each group
      the number of patients who received blood transfusions and when blood
      transfusions occurred, before or after the 15th day of life, was recorded. There
      was a statistically significant difference only for transfusions carried out
      after the 15th day of life (p < 0.002). No adverse effects attributable to rHuEpo
      during the treatment were noted. The results indicate that early rHuEpo
      treatment, in combination with iron supplements, is effective in reducing the
      need for blood transfusions in preterm infants after the 15th day of life.

PMID- 9783308
TI  - Familial medulloblastoma.
AB  - Medulloblastomas account for 20% of all primary brain tumors. The vast majority
      of them are sporadic. Familial medulloblastoma is very rare--only a few cases
      have been reported worldwide. Most were observed in siblings of the same sex. The
      affected children presented at various ages and all of them have died, usually
      within the first 2 years following diagnosis. The authors describe a case of
      familial medulloblastoma with unusual characteristics: Two siblings of different
      sex and a second-degree relative have presented at exactly the same age of 18
      months. The histologic pattern was the same in all patients, that of desmoplastic
      medulloblastoma. All patients are alive and remain in remission 12, 5, and 11
      years, respectively, after diagnosis. The genetics and the pathogenesis of the
      disease remain obscure.

PMID- 9783309
TI  - Ataxia telangiectasia associated with B-cell lymphoma: the effect of a half-dose
      of the drugs administered according to the acute lymphoblastic leukemia standard
      risk protocol.
AB  - Ataxia telangiectasia (A-T) is a rare autosomal recessive disorder characterized
      by cerebellar ataxia, oculocutaneous telangiectasia, and variable degrees of
      humoral and cellular immunodeficiency. Affected individuals are known to exhibit
      a high incidence of lymphoma and leukemia. Because of increased chemosensitivity,
      the treatment of A-T patients with malignancies requires extremely careful
      planning and caution with respect to the use of chemotherapy. The authors report
      on a 12-year-old boy with A-T who developed B-cell lymphoma. He received a half
      dose of the drugs administered according to the acute lymphoblastic leukemia
      (ALL) protocol issued by our children's cancer study group (9104 Standard Risk
      Protocol, Tokai Pediatric Oncology Study Group). As a result, he continues to be
      in complete remission and free of treatment complications 32 months after the
      diagnosis of B-cell lymphoma.

PMID- 9783310
TI  - Shift from fetal to adult hemoglobin production in a preterm infant after
      exchange transfusion: a quantitative approach.
AB  - To evaluate the quantitative aspects of the shift in production from fetal
      hemoglobin (HbF) to adult hemoglobin (HbA), the HbF and HbA mass were estimated
      in a preterm infant (gestational age 29 weeks) for 22 weeks after an exchange
      transfusion the second day of life, leading to an initial HbA% of 100. Up until
      the estimated time of delivery, the HbA mass declined continuously, at a rate
      corresponding to a survival time of the transfused HbA erythrocytes of 100 days,
      and the rise in total hemoglobin mass could be ascribed solely to a rise in the
      HbF mass. HbF% maximum was reached 3 weeks before HbF mass maximum, and, thus,
      the HbF% and HbA% time courses gave no basis for evaluation of the
      production/destruction balance of HbF and HbA erythrocytes. The applied
      quantitative approach seems to be a useful additional procedure for evaluating
      the switch from HbF to HbA production and for estimating HbA erythrocyte survival
      time in preterm infants.

PMID- 9783312
TI  - Avascular necrosis of the femoral head in neuroblastoma: a case report.
AB  - Avascular necrosis of bone is a well-described complication of cancer
      chemotherapy containing corticosteroids, and has been observed in lymphomas and
      acute lymphoblastic leukemia. Avascular necrosis occurring in association with
      neuroblastoma has never been reported before. This study reports on a 7-year-old
      boy with stage IV neuroblastoma developing avascular necrosis of the femoral head
      of both hips during treatment with combination chemotherapy using
      cyclophosphamide, cisplatin, etoposide, and doxorubicin. He was given
      conservative treatment in view of the progressive disease.

PMID- 9783311
TI  - Case report: a preterm infant with an extradural myxopapillary ependymoma
      component of a teratoma and high levels of alpha-fetoprotein.
AB  - The sacrococcygeal region may be the origin of germinal tumors, of
      paragangliomas, and, rarely, of extradural myxopapillary ependymomas (MPE) in the
      newborn and child. A case is presented of a preterm child with an abdominal
      tumor, originating from the precoccygeal area, that turned out to be a teratoma
      with a component of an MPE. The high levels of alpha-fetoprotein in this preterm
      baby were initially misleadingly interpreted as a tumoral marker. The
      differential diagnosis and the difficulties in interpreting tumoral markers in
      infants are discussed.

PMID- 9783313
TI  - Cobalamin deficiency presenting with cutaneous hyperpigmentation: a report of two
      siblings.
AB  - The authors report on 2 children with pernicious anemia, sisters, who presented
      with hypermelanosis as one of the clinical manifestations. The hypermelanosis
      disappeared with adequate treatment of vitamin B12 deficiency. Vitamin B12
      deficiency should be considered in the differential diagnosis of a child
      presenting with hyperpigmentation and macrocytic red cell indices.

PMID- 9783314
TI  - Hodgkin's disease in a child with hyperimmunoglobulin E syndrome.
AB  - A 10-year-old boy with hyperimmunoglobulin E (HIE) syndrome was admitted to the
      hospital due to intermittent fever and a growing neck mass noted for 3 months. He
      had had chronic eczema and recurrent skin infections since infancy. At age 8, the
      diagnosis of HIE was established when a pneumatocele was found in the presence of
      extremely elevated serum IgE levels (7842 IU/mL). He also had defective T
      lymphocyte function, manifested by cutaneus anergy, as well as abnormal
      proliferative response to mitogenic stimuli. Chemotactic function of neutrophils
      was normal. Pathological examination of the lymph node disclosed Hodgkin's
      disease (nodular sclerosis). A high index of suspicion for lymphoma should be
      given in patients with HIE syndrome who present with lymph node enlargement.

PMID- 9783315
TI  - Small-bowel volvulus during treatment for renal tumors.
AB  - Intestinal obstruction as a result of postnephrectomy adhesions occurs in up to
      7% of children treated for Wilms' tumor. The authors report two children who
      developed small-bowel volvulus during the treatment of their renal tumor. Both
      underwent urgent resection of their ischemic bowel with primary anastamosis and
      are long-term survivors. The risk of this complication may be increased in young
      children with bulky tumors who receive abdominal radiotherapy.

PMID- 9783316
TI  - Necrotizing otitis externa, otitis media, peripheral facial paralysis, and brain
      abscess in a thalassemic child after allogeneic BMT.
AB  - Severe infection is one of the major complications in the early and late post
      bone marrow transplantation period. The authors report a thalassemic child who
      developed necrotizing otitis externa and otitis media, a very rare complication
      after bone marrow transplantation, and then peripheral facial nerve paralysis and
      brain abscess in the early period of bone marrow transplantation despite
      antibacterial and antifungal prophylaxis. Necrotizing otitis media is
      characterized by necrosis and sloughing of considerable areas in the middle ear
      and adjacent tissues and is an unusual disorder because of today's antibiotics.
      Granulocytopenia and background ear tissue exposed to previous repeated otitis
      media attacks may be the predisposing factors in this case. The authors conclude
      that the children with previous histories of recurrent otitis media should be
      prepared and monitored very carefully during bone marrow transplantation because
      of the risk of necrotizing otitis media, especially in the granulocytopenic
      period.

PMID- 9783317
TI  - Multiple fungal brain abscess in a child with acute myeloblastic leukemia.
AB  - Fungal brain abscess is rarely cured in childhood. The mortality rate is higher
      than 95% in immunocompromised patients, even if antifungal agent and surgery are
      used. A 5-year-old boy with acute myeloblastic leukemia (AML) (M2 according to
      FAB classification) and multiple candidal brain abscesses is discussed. The
      candidal brain abscesses of this patient were thought to be iatrogenic, due to
      the difficult lumbar puncture of intratechal therapy. He was successfully treated
      with combination conventional amphotericin B (ABC), surgical drainage, and
      granulocyte colony-stimulating factor. Toxicity was not determined due to ABC.
      This is thought to be the first child to survive AML and multiple candidal brain
      abscesses.

PMID- 9783318
TI  - About the von Willebrand factor.

PMID- 9783319
TI  - Granulocyte-macrophage colony stimulating factor (GM-CSF) in malignancy.

PMID- 9783321
TI  - Glucose tolerance and serum insulin levels in an animal model of obesity induced
      by the antipsychotic drug, sulpiride.
AB  - To assess the role of insulin in the development of obesity induced by
      antipsychotic drugs, a glucose tolerance test was conducted in 40 female rats
      during the peak of sulpiride-induced weight gain and in 40 vehicle-treated
      animals. The glucose area under the curve did not differ between the groups (P =
      0.24), however, the area under the insulin curve was significantly decreased by
      sulpiride (55.2 +/- 2.8 versus 115.6 +/- 18.9, P = 0.007). The results suggest
      that insulin resistance and hyperinsulinaemia are not involved in the excessive
      weight gain observed in this animal model of drug-induced obesity. Alternatively,
      the insulin-dampened response observed in the sulpiride-treated rats may be
      related to increased insulin sensitivity, which may promote weight gain as
      proposed by Ravussin (1995).

PMID- 9783320
TI  - In vitro screening for metabolic interactions among frequently occurring binary
      mixtures of volatile organic chemicals in Norwegian occupational atmosphere.
AB  - Surveys of Norwegian industrial occupational atmosphere between 1983 to 1996,
      have identified the 12 most frequent occurring binary combinations of volatile
      organic chemicals. These combinations were tested in vitro for mutual inhibition
      or enhancement of metabolism by the head space vial equilibration technique with
      liver S9 obtained from in vivo untreated or pretreated (with the binary mixture)
      rats. The in vitro system responded to in vivo pretreatment by increasing the
      metabolic rate of several potentially toxic organic chemicals such as toluene,
      xylene, styrene, and dichloromethane. In untreated liver S9, the metabolism of
      several of the tested binary pairs was inhibited when coexposed in vitro to their
      most prevalent follower as shown for instance for ethanol (with ethyl acetate),
      dichloromethane (with styrene) and mutually between toluene and xylene. This
      inhibitory effect disappeared, however, for several of the solvents when combined
      with the in vivo induced liver S9, a situation which may be the most relevant for
      occupational exposure. It is concluded that several metabolic interactions occur
      between low-molecular weight volatile chemicals found in occupational air. These
      are both inductive and inhibitory in nature and a further mechanistic evaluation
      including a higher number of differentiated dosage levels, must be performed
      before a possible health hazard can be confirmed or rejected for the investigated
      combinations.

PMID- 9783322
TI  - Adriamycin induces protein oxidation in erythrocyte membranes.
AB  - Adriamycin is an anthracycline antineoplastic agent whose clinical effectiveness
      is limited by severe side effects, including cardiotoxicity. A current hypothesis
      for adriamycin cardiotoxicity involves free radical oxidative stress. To
      investigate this hypothesis in a model system, we applied the technique of
      immunochemical detection of protein carbonyls, known to be increased in oxidized
      proteins, to study the effect of adriamycin on rat erythrocyte membranes.
      Erythrocytes obtained from adriamycin-treated rats demonstrated an increase of
      carbonyl formation in their membrane proteins. Yet, in separate experiments when
      adriamycin was incubated with rat erythrocyte ghosts, there was no significant
      increase of membrane protein carbonyls detected. In contrast, isolated
      erythrocytes incubated with an adriamycin-Fe3+ complex exhibited a robust
      carbonyl incorporation into their membrane proteins in a time-dependent manner.
      The level of carbonyl formation was dependent upon the concentration of Fe3+
      known to form the adriamycin-Fe3+ complex. When the time course between protein
      carbonyl formation and lipid peroxidation was compared, protein carbonyl
      detection occurred earlier than lipid peroxidation as assayed by thiobarbituric
      acid reactive substances formation. These results are consistent with the notion
      that oxidative modification of membrane proteins may contribute to the
      development of the acute adriamycin-mediated toxicity.

PMID- 9783323
TI  - Detection of styrene and styrene oxide-induced DNA damage in various organs of
      mice using the comet assay.
AB  - Styrene (100-500 mg/kg b.wt.) and styrene oxide (50-200 mg/kg b.wt.) were given
      as a single intraperitoneal injection to female mice (C57BL/6) at various time
      intervals before sacrifice. Primary DNA damage in various organs was studied
      using alkaline single cell gel electrophoresis (comet) assay. Both substances
      induced significant DNA damage in lymphocytes, liver, bone marrow and kidney
      after 4 hr. The lymphocytes and liver cells were found to be the most sensitive
      cells to the DNA damaging effects of both agents. With the exception of bone
      marrow cells, the degree of DNA damage in all other cell types was decreased from
      4 hr to 16 hr after the administration of both compounds. A strong sublinear dose
      response relationship was observed in the lymphocytes, liver and bone marrow
      cells, possibly indicating a saturation of the detoxifying enzyme systems in
      these organs. The present work suggests that the comet assay can be used for
      detection of primary DNA damage induced by styrene and styrene oxide in vivo and
      for comparing the sensitivity of various target organs.

PMID- 9783324
TI  - Variations of arterial responses in vitro in different sections of rat main
      superior mesenteric artery.
AB  - We examined the control of vascular tone in rat main superior mesenteric artery.
      Three standard rings (3 mm in length) of the mesenteric artery were cut,
      beginning 5 mm, 13 mm and 21 mm distally from the mesenteric arteryaorta
      junction. In noradrenaline-precontracted rings, relaxations to acetylcholine in
      the absence and presence of the cyclooxygenase inhibitor diclofenac, did not
      differ in the studied sections. However, the nitric oxide synthase inhibitor, NG
      nitro-L-arginine methyl ester, attenuated the diclofenac-resistant responses to
      acetylcholine more effectively in the proximal than the distal section.
      Glibenclamide, an inhibitor of ATP-sensitive K+ channels, diminished relaxations
      evoked by acetylcholine only in the distal section, whereas the inhibitor of Ca2+
      activated K+ channels, apamin, attenuated the responses in all sections.
      Furthermore, relaxation sensitivity to nitroprusside and isoprenaline was lower
      in the proximal than distal section. Arterial contractile sensitivity to
      noradrenaline and potassium chloride was higher, while the maximal contractile
      force generation was lower in the proximal than the distal part. In conclusion,
      in different sections of rat main superior mesenteric artery considerable
      variability was observed in vasoconstrictor and vasodilator responses, as well as
      in the contribution of endothelial nitric oxide and endothelium-mediated
      hyperpolarization to vasodilation. Therefore, the present results emphasize the
      fact that only corresponding vessel segments should be used when investigating
      the control of arterial tone.

PMID- 9783325
TI  - Role of microtubules in glucose uptake by C6 glioma cells.
AB  - Drugs that influence tubulin function were used to investigate the role of
      microtubules in hexose uptake by C6 glioma cells. In C6 cells, colchicine and
      vinblastine (which inhibit tubulin polymerization) inhibited radioactive [3H]2
      deoxy-D-glucose uptake by about 30%. Paclitaxel (which promotes tubulin
      polymerization) stimulated hexose uptake by about 25%. To further demonstrate
      that microtubules play a role in hexose uptake, C6 cells were transfected with
      GLUT1 cDNA and then challenged with 100 nM paclitaxel. In GLUT1-transfected cells
      paclitaxel stimulated 2-deoxy-D-glucose uptake by about 35%. To study the role of
      tubulin in agonist-stimulated hexose uptake, the effect of colchicine on
      carbachol-induced uptake was next examined. Hexose uptake was increased with
      carbachol in concentration-dependent manner which was abolished by pretreatment
      with colchicine. To examine the specificity of the inhibitory effect of
      colchicine on G protein-mediated signal transduction pathway, the influence of
      colchicine on insulin (which acts via tyrosine kinase pathway) stimulation of 2
      deoxy-D-glucose uptake was investigated. Hexose uptake was increased by insulin
      in a concentration-dependent manner which was unaffected by pretreatment with
      colchicine. These results suggest that microtubules are involved in basal and
      carbachol-stimulated glucose uptake by C6 cells.

PMID- 9783326
TI  - An investigation of the possible interaction of clomethiazole with glutamate and
      ion channel sites as an explanation of its neuroprotective activity.
AB  - The activity of the neuroprotective agent clomethiazole at glutamate and ion
      channel sites has been investigated. Dizocilpine (3.25 mg/kg intraperitoneally)
      provided almost total protection against the damage produced by infusion of N
      methyl-DL-aspartate (NMDLA; 75 micrograms) into the right hippocampus. In
      contrast, clomethiazole (96 mg/kg intraperitoneally) was without effect. Using
      ligand binding techniques, no evidence was found for clomethiazole interacting
      with NMDA, AMPA or sigma binding sites. Clomethiazole did inhibit the stimulatory
      effect of the metabotropic glutamate receptor agonist 1S3R-aminocyclopentone-1,3
      dicarboxylic acid (ACPD) on phosphoinositol hydrolysis, but only at a
      concentration of 10(-3) M, which is unlikely to have functional relevance.
      Clomethiazole was also without effect on ligand binding to Ca2+ channels (N- or L
      type), Na+ channels or ATP-sensitive K+ channels. Potentiation of GABA function
      therefore remains the most plausible explanation for the neuroprotective activity
      of clomethiazole.

PMID- 9783327
TI  - delta-Aminolevulinate dehydratase inhibition by 2,3-dimercaptopropanol is
      mediated by chelation of zinc from a site involved in maintaining cysteinyl
      residues in a reduced state.
AB  - The mechanisms underlying mouse delta-aminolevulinate dehydratase (ALA-D)
      inhibition by a chelating agent used in the treatment of heavy metal poisoning,
      2,3-dimercaptopropanol (British Anti-Lewisite), were investigated. ALA-D
      inhibition by 2,3-dimercaptopropanol was totally reversed by 25-100 microM Zn2+,
      indicating that inhibition was due to chelation of zinc by 2,3
      dimercaptopropanol. Our data suggested that zinc bound to a labile site
      (displaced by 25-40 microM EDTA or 500 microM 2,3-dimercaptopropanol) is involved
      in maintaining the sulfhydryl groups of ALA-D in a reduced state (essential for
      enzyme activity), since inhibition by these compounds was reversed by 10 mM
      dithiotreitol (a reducing agent). On the other hand, 10 mM dithiotreitol did not
      reverse ALA-D inhibition by a higher concentration of EDTA (100 microM).
      Accordingly, 2,3-dimercaptopropanol appears to inhibit ALA-D through a mechanism
      similar to that of low EDTA concentrations. Neither oxidized 2,3
      dimercaptopropanol nor reactive oxygen species appeared to contribute for ALA-D
      inhibition by reduced 2,3-dimercaptopropanol. Taken together, these results
      suggest that 2,3-dimercaptopropanol inhibits ALA-D by chelating Zn2+ from a
      labile site that is involved in maintaining enzyme sulfhydryl groups in a reduced
      state. This site is compatible with the ZnB or Zn beta previously described in
      mammalian and bacterial ALA-D.

PMID- 9783328
TI  - Apoptosis in embryos of diabetic rats.
AB  - The aim of the present study was to determine whether maternal diabetes affects
      rat embryo and yolk sac apoptosis during the postimplantation period. Severely
      malformed and growth-retarded embryos of gestational day 12 from diabetic rats
      exhibited pronounced DNA laddering on agarose gels. On the other hand, no DNA
      laddering could be observed in any of the non-malformed embryos from control and
      diabetic rats, or in their corresponding yolk sacs. Analysis of embryos of
      gestational day 10 revealed only a few scattered TUNEL positive cells mainly
      located in the allantois, the foregut epithelium, the cranial neuroepithelium and
      in the cranial mesenchyme. Embryonic tissue of gestational day 12 showed numerous
      aggregates of TUNEL-positive cells, indicating developmental remodelling of
      multiple organs. Analysis of non-malformed embryos of day 10 and 12 revealed a
      distribution and frequency of TUNEL positive cells unaffected by the diabetic
      state of the mother on both days. In vitro incubation (2-8 hr) of normal day-12
      yolk sacs resulted in strong DNA laddering, but not in the corresponding embryos.
      Dispersed yolk sac cells generated higher levels of reactive oxygen species than
      dispersed embryonic cells. Reactive oxygen species levels in both embryonic and
      yolk sac cells were unaffected by the diabetic state of the mother. Moreover,
      immunoblot analysis showed high Bcl-2 and undetectable caspase-1 levels in
      embryos from both normal and diabetic rats and low Bcl-2 and high caspase-1
      levels in the corresponding yolk sacs. Immunohistochemical analysis of embryos
      demonstrated caspase-1-reactivity in a small subpopulation of cells located in
      proximity to TUNEL-positive cells. We conclude that the inherent capacity of
      embryonic cells to enter apoptosis in vitro is low as compared to yolk sac cells,
      and that wide-spread apoptosis is not likely to play a major role in diabetes
      induced dysmorphogenesis but rather in early phases of resorption of severely
      malformed and developmentally retarded embryos.

PMID- 9783329
TI  - Respiratory effects in mice exposed to airborne emissions from Stachybotrys
      chartarum and implications for risk assessment.
AB  - Stachybotrys chartarum, a mycotoxin producing mould found in some damp buildings,
      was grown in aluminum dishes in closed exposure chambers. The loading factor,
      5.12 m2/m3, corresponded to 2.8 times the loading in a normal room with all
      surfaces covered by mould. Sensory irritation, bronchoconstriction and pulmonary
      irritation effects were investigated using a sensitive mouse bioassay in which
      the airway reactions were measured plethysmographically. Little effect was seen
      from the vapours in agreement with the predicted effects of the low
      concentrations of volatile organic compounds measured. Even under the influence
      of an airflow about four times that measured in normal buildings, the
      concentration of liberated spores and other particles was very low, corresponding
      to the biological effects observed, and probably reflecting the high water
      content of the substrate. These results demonstrate that many factors are
      important for the transport of biologically active mould metabolites from
      building material to occupants and that no direct relationship may exist between
      immediate biological effects and surface area covered with mould. Therefore, risk
      assessments should be based on estimated effects of emitted vapours, effects of
      liberated particles, e.g. sensitization potentials of the mould spores and
      effects of the generated metabolites (mycotoxins).

PMID- 9783330
TI  - Effects of lead exposure on licking and yawning behaviour in rats.
AB  - In the present study, effects of lead exposure on licking and yawning behaviour
      have been studied. The dopaminergic receptor agonist, apomorphine (0.15, 0.25 and
      0.5 mg/kg), induced dose-dependent licking in rats. The maximum response was
      obtained with 0.5 mg/kg of the apomorphine. Lead acetate (0.05%) exposure
      significantly increased apomorphine-induced licking. Yawning induced by the D2
      dopaminergic agonist, bromocriptine (2, 3, 4, 8 mg/kg), and the cholinergic drug,
      physostigmine (0.1 or 0.3 mg/kg), was significantly decreased by lead acetate
      (0.05%) exposure. It may be concluded that the behaviour induced by dopaminergic
      or cholinergic agents can be affected by lead subchronic exposure.

PMID- 9783331
TI  - Accumulation of bisphosphonates in human artery and their effects on human and
      rat arterial function in vitro.
AB  - Clodronate, etidronate and pamidronate are bisphosphonates introduced in the
      treatment of hypercalcaemia and osteoporosis. Interestingly, they also inhibit
      development of experimental atherosclerosis and affect smooth muscle tone of
      isolated rat tail artery. We have studied in vitro whether these hydrophilic
      compounds 1) accumulate in the wall of the human artery, 2) influence human
      arterial tone, and 3) interfere with the vascular action of L-type Ca2+
      antagonists. Human internal mammary artery rings were incubated with 14C-labelled
      bisphosphonates. After a 2-hr incubation, the ratios of artery-to-incubate
      concentrations with 4 and 40 mumol/l of clodronate were, respectively, 3.0 +/-
      0.5 (mean +/- S.E.M.) and 1.3 +/- 0.2, with 4 and 40 mumol/l of etidronate 7.4 +/
      0.9, and 3.2 +/- 0.4, and with 0.4 and 4 mumol/l of pamidronate 4.7 +/- 0.7 and
      3.9 +/- 0.8. Both tested bisphosphonates, clodronate and pamidronate, reduced the
      arterial contractile force induced by alpha-adrenergic stimulation with
      noradrenaline and membrane depolarization with high concentration of KCl.
      Clodronate also decreased the arterial contraction induced by cumulative addition
      of Ca2+ with KCl as the agonist, and had an additive inhibitory effect on this
      response with the L-type Ca2(+)-channel blocker nifedipine. The results
      demonstrate that 1) bisphosphonates accumulate markedly in human artery, 2)
      clodronate and pamidronate reduce human arterial contactile force to alpha
      adrenergic and depolarizing stimuli, and 3) as shown with clodronate,
      bisphosphonates may exert an additive inhibitory effect on human arterial
      contractions with an L-type Ca2(+)-channel blocker.

PMID- 9783332
TI  - Pharmacokinetics and oral bioavailability of glycopyrrolate in children.
AB  - Based on plasma levels determined with a radioreceptor assay and following a
      single oral (50 micrograms/kg) and intravenous (5 micrograms/kg) administration
      of glycopyrrolate in six healthy children operated twice during a several weeks
      period, a negligible and variable oral bioavailability was found (3.3; 1.3-13.3%)
      (median;range). No significant changes in heart rate after oral or intravenous
      administration of the drug could be seen. Oral glycopyrrolate appears to have no
      place in paediatric premedication.

PMID- 9783333
TI  - The effect of dexamethasone on the pharmacokinetics of triazolam.
AB  - The effects of short-term use of a small dose of dexamethasone on the
      pharmacokinetics and pharmacodynamics of the CYP3A4 substrate, triazolam, were
      examined. In a randomized, double-blind cross-over study with two phases, ten
      healthy volunteers were given either 1.5 mg dexamethasone or placebo once a day
      for 4 days. On the 5th day, 0.5 mg triazolam was administered orally. Plasma
      triazolam concentrations and effects of triazolam were measured for 10 hr.
      Dexamethasone did not have statistically significant effects on the
      pharmacokinetics of triazolam. The mean total area under the plasma triazolam
      concentration-time curve was, however, 19% smaller during the dexamethasone phase
      than during the placebo phase (11.4 +/- 5.7 ng ml-1 hr versus 14.1 +/- 8.8 ng ml
      1 hr (mean +/- S.D.); P = 0.09). The four psychomotor tests employed did not show
      significant differences in the effects of triazolam between the phases. Although
      dexamethasone had only small effects on the pharmacokinetics and pharmacodynamics
      of triazolam in the present study, higher doses or prolonged use of dexamethasone
      might cause a more pronounced induction of CYP3A4. Further studies on the effects
      of dexamethasone on the pharmacokinetics of CYP3A4 substrates in man are needed.

PMID- 9783334
TI  - Lack of effect of leptin on the behaviour of mice predicting the level of anxiety
      and depression.

PMID- 9783335
TI  - The normal association between newly replicated DNA and the nuclear matrix is
      abolished in cells infected by herpes simplex virus type 1.
AB  - In cells infected by herpes simplex virus type 1 (HSV1), a series of nuclear
      changes can be observed in a temporal sequence. Such changes are related to
      important modifications in the higher-order structure of host cell chromatin,
      such as loss of DNA loop supercoiling and wholesale DNA loop disorganization. It
      is known that the topological relationship between DNA and the nuclear
      substructure is a critical factor for proper nuclear physiology. Here we report
      that the usual association between newly replicated DNA and the nuclear
      substructure, commonly known as nuclear matrix, is abrogated in cells infected by
      HSV1, thus establishing a correlation between the virus-induced modifications in
      chromatin higher-order structure and a major biochemical change within the
      infected cell nucleus.

PMID- 9783336
TI  - Genotyping HCV isolates from Italy by type-specific PCR assay in the core region.
AB  - A revision of the polymerase chain reaction (PCR) core procedure was performed
      for genotyping hepatitis C virus (HCV) in 139 patients from Italy. This
      procedure, developed prior to the identification of new genotypes, may be
      inadequate in several geographical areas. We proposed a new typing mixture in
      which primers for types 2c and 4, that are reported to be circulating in Italy,
      were added and a primer for type 2b was substituted. Using the modified
      procedure, 139 HCV-positive patients were analysed. The HCV genotype was
      identified in 96.4% of the cases. We observed double infections and unclassified
      genotypes in 5 (3.6%) and 5 (3.6%) patients, respectively. The classification of
      isolates into genotypes and subtypes 2b, 2c and 4 was confirmed by sequence
      analysis. Furthermore, the efficiency and accuracy of the modified core procedure
      were evaluated by parallel testing of 107 out of 139 samples using the line probe
      assay, and demonstrated a 98.9% degree of concordance. The results demonstrated
      the specificity of the selected primers for type 2c, 2b and 4 and confirmed the
      circulation of types 2c and 4 in Italy. In conclusion, the proposed modified PCR
      procedure is the only primer-specific PCR genotyping method available for
      identification of the 2c and 4 genotypes reported to be circulated in Italy and
      other European countries.

PMID- 9783337
TI  - Rapid genotyping of hepatitis C virus by direct cycle sequencing of PCR-amplified
      cDNAs and capillary electrophoresis analysis.
AB  - There is an increasing demand for the genotyping of hepatitis C virus (HCV),
      since it has been shown that different HCV genotypes are associated with distinct
      profiles of pathogenicity and responses to antiviral treatment. Hence, there is a
      need for a simple and precise genotyping assay for routine diagnosis of HCV types
      and subtypes. Here we show that direct sequencing, considered as the reference
      method, can provide an accurate and rapid method for large-scale screening of HCV
      genotypes. PCR-amplified cDNAs of the HCV 5' non-coding region (5' NCR) were
      obtained from the widespread "Amplicor" HCV detection system. Semi-purified PCR
      products were directly cycle-sequenced in a single tube using multicolour dye
      terminator chemistry. Sample loading, electrophoresis and sequence analysis were
      automatically achieved by a capillary electrophoresis-based genetic analyser. Out
      of a total of 500 samples, HCV subtype 1b accounted for the majority of the
      infections (41%), followed by HCV 3 (31%) and HCV 1a (22%). This procedure failed
      to identify a genotype in only 3 samples. In addition, several cases of mixed HCV
      infection were also documented. The combination of direct cycle sequencing of PCR
      products with capillary electrophoresis provides a simple and rapid method
      convenient for routine HCV genotyping analysis.

PMID- 9783338
TI  - Transplacental transmission of hepatitis C virus in HIV-negative mothers.
AB  - The aim of this work was to evaluate transplacental transmission of hepatitis C
      virus (HCV) in HIV-negative pregnant women who were HCV-PCR-positive, and also to
      determine the serotypes of the virus in these cases. Therefore, 767 pregnant
      women were screened for anti-HCV antibodies, hepatitis B surface antigen (HBsAg)
      and anti-HIV antibodies. HCV PCR was performed for HCV-positive women. Those who
      were PCR-positive were tested for anti-HCV IgM. Neonates of PCR-positive mothers
      were tested for virus transmission by the PCR test. Virus serotyping was done for
      mothers and neonates. Anti-HCV antibodies were detected in 105 out of 767 (13.7%)
      pregnant women. PCR was positive in 18 out of 67 HCV-positive women (26.9%).
      Transplacental transmission occurred in 11.1% of HIV-negative pregnant women. HCV
      type 4 predominates in Egypt (83.3%). Mothers who are PCR-positive and have high
      aspartate aminotransferase and positive anti-HCV IgM are most likely to transmit
      HCV to their babies.

PMID- 9783340
TI  - Adverse pregnancy outcome in schizophrenic women: occurrence and risk factors.
AB  - Low birth weight and preterm birth are important predictors of infant mortality
      and morbidity, and may increase the risk of schizophrenia. These adverse outcomes
      of pregnancy could be associated, therefore, with increased risk in children
      genetically predisposed to schizophrenia. The aim of this review was to describe
      the occurrence of risk factors for low birth weight, preterm birth, and perinatal
      death among schizophrenic women, and to describe the incidence of those adverse
      pregnancy outcomes among schizophrenic women. Smoking, substance abuse, and low
      socioeconomic status are associated with fetal growth retardation, preterm birth,
      and perinatal death, and also with schizophrenia. Therefore, increased incidence
      of adverse pregnancy outcome should be expected in schizophrenic women. The
      available evidence suggests that schizophrenic women are at increased risk of
      delivering infants with low birth weight, but the existing studies are of small
      statistical power. Preterm birth and perinatal death have only been investigated
      little among schizophrenic women. An important focus of future research should be
      to establish the risk of adverse pregnancy outcome, and to study the association
      between the suspected risk factors and pregnancy outcome in schizophrenic women.
      In clinical work with pregnant schizophrenic women, efforts should be made to
      prevent exposure to suspected risk factors like smoking, substance use, and
      socioeconomic problems. This could possibly decrease the mortality and morbidity,
      including the risk of schizophrenia in the offspring, and clarify the importance
      of environmental and genetic factors in the etiology of schizophrenia.

PMID- 9783339
TI  - Dengue encephalitis in French Guiana.
AB  - Thousands of cases of dengue fever (DF) and several cases of dengue haemorrhagic
      fever were recorded in French Guiana during the recent outbreak of dengue-2 virus
      (1991-1992) and in subsequent years. One case with clinical signs typical of
      classical DF with neurological complications is reported in this study. The
      neurological features (encephalitis) appeared during the acute phase, 2 days
      after the onset of fever. Dengue-2 virus was detected in both the cerebrospinal
      fluid and blood sample. This case was fatal. This first reported case of
      classical DF with encephalitis in French Guiana is a new demonstration of the
      potential neurovirulence of dengue viruses.

PMID- 9783341
TI  - Characteristics of early- and late-diagnosed schizophrenia: implications for
      first-episode studies.
AB  - First-episode studies of schizophrenia are being carried out in many places.
      However, previous work has suggested that only half of the patients with
      schizophrenia receive the diagnosis in the initial stages of the illness. We
      examined whether cases of early- and late-diagnosed schizophrenia differed with
      respect to key sociodemographic characteristics and indicators of service use
      that might bias first-episode studies. Individuals who (i) presented for the
      first time between 1983 and 1993 to psychiatric services in a defined urban area
      with a cumulative mental health case register; and (ii) received a diagnosis of
      schizophrenia at least once during their mental health career were identified (n
      = 186). This sample was divided into those who received the diagnosis of
      schizophrenia for the first time within the first year of service contact (early
      diagnosed schizophrenia; EDS), and those who received it for the first time after
      the first year of service contact (late-diagnosed schizophrenia; LDS). The 10
      year incidence of EDS and LDS were 10.4 and 7.0 per 100,000 person-years,
      respectively. EDS and LDS did not differ in their pattern of association with
      sex, single marital status and higher levels of neighbourhood socioeconomic
      deprivation. However, EDS was more incident in the higher age groups, and the
      level of service use was higher for EDS cases in the first years of contact with
      mental health services, with LDS cases gradually catching up and exceeding EDS
      service use later in the illness course. Although differences between EDS and LDS
      were few, studies of patients with schizophrenia in the 'first' episode are
      likely to be most representative if patients who receive the diagnosis for the
      first time after previous episodes of care for non-schizophrenic episodes are
      also included.

PMID- 9783342
TI  - Left nostril olfactory identification impairment in a subgroup of male patients
      with schizophrenia.
AB  - Abnormal structural brain asymmetries have been reported in schizophrenia in
      brain areas which overlap with olfactory processing regions, with abnormalities
      more often described within the left hemisphere. We attempted to determine
      whether the olfactory agnosia observed in some male patients with schizophrenia
      was more likely left-hemisphere based. We assessed unirhinal (single nostril)
      olfactory identification and detection threshold in 65 male patients who met DSM
      IV criteria for the diagnosis of schizophrenia and 59 healthy male control
      subjects. A two-way, mixed-design ANCOVA with diagnosis as the between-group
      factor, nostril as the within-subject factor and age as covariate was used to
      compare olfactory identification ability. This analysis demonstrated that
      patients with schizophrenia performed more poorly than the healthy controls
      across nostrils, but no differences were observed in either group between
      nostrils. However, when patients were classified according to unirhinal olfactory
      status (impaired left < right, impaired right < left, normosmic left < right,
      normosmic right < left), impaired patients were more than twice as likely to be
      classified as having a left nostril disadvantage than right nostril disadvantage.
      In contrast, within the normosmic group of patients, this pattern was reversed.
      Moreover, when those patients whose unirhinal olfactory scores differed by less
      than two points were removed from the analysis, a 2:1 ratio of left < right
      versus right < left was observed in the impaired patients. These results suggest
      that for impaired male patients with schizophrenia, olfactory identification
      deficits are more likely found for the left nostril, perhaps indicative of
      abnormalities in olfactory processing within the left hemisphere.

PMID- 9783343
TI  - Mini-Mental State Examination (MMSE) performance of partially remitted community
      dwelling patients with schizophrenia.
AB  - Patients with schizophrenia perform worse than healthy controls on many neuro
      psychological tests. However, previous studies of neuro-cognitive function have
      mostly been carried out on acutely ill or institutionalized patients. The
      objective of this study was to generate norms for performance of partially
      remitted community-dwelling patients with schizophrenia on the Mini-Mental State
      Examination (MMSE). Partially remitted outpatients attending a depot
      antipsychotic clinic or a clozapine clinic (n = 272) were tested using the MMSE.
      Demographic and clinical characteristics associated with MMSE performance, as
      well as the performance of specific items, were examined. MMSE score was
      significantly associated with educational status and race. Patients in our sample
      performed approximately 2-3 points below the population norms at all ages, but
      the mean score for the group was not in the impaired range. There was no apparent
      widening of this gap with advancing age. Patients who did poorly most frequently
      had difficulty with memory, attention and construction tasks. The MMSE is easy to
      administer to outpatients with schizophrenia and most patients score in the un
      impaired range. The MMSE may be used to identify a subgroup of patients who score
      in the impaired range, for further investigations.

PMID- 9783344
TI  - Selective attention in schizophrenia: relationship to verbal working memory.
AB  - In previous work using the Stroop task to examine cognitive function in
      schizophrenia, we have suggested that reaction time (RT) facilitation and error
      interference should be more sensitive measures of cognitive function than RT
      interference. We examined this hypothesis in 36 DSM-IV schizophrenia and
      schizoaffective patients, who performed both the Stroop and the Speaking Span, a
      measure of verbal working memory. The results supported our hypotheses,
      demonstrating that RT facilitation and error interference were associated more
      strongly with working memory performance than RT interference. The robust
      correlations between these measures of selective attention and Speaking Span
      performance has implications for understanding the nature and selectivity of
      cognitive dysfunction in schizophrenia. We present several different hypotheses
      that may explain this relationship, including: (1) a generalized deficit; (2) a
      common cognitive disturbance; and (3) a common neurobiological dysfunction.

PMID- 9783345
TI  - The relationship between symptoms and insight in schizophrenia: a longitudinal
      perspective.
AB  - It has been suggested that deficits in symptom awareness and attribution in
      schizophrenia are relatively independent of core symptoms of the disorder. Many
      studies report conflicting findings, however, which may be explained by
      differences in study design and target population. In this study 33 individuals
      with schizophrenia or schizoaffective disorder were assessed longitudinally using
      standard symptom and insight measures, with analyses focusing on associations
      with psychotic, depression and anxiety symptoms. Both cross-sectional and
      longitudinal analyses showed significant but only moderate associations between
      insight and symptoms of depression and disorganization, with no consistent
      relationships with positive and negative symptoms. Higher levels of depression
      were associated with improved awareness and attribution, whereas higher levels of
      disorganized symptoms were associated with deficits in awareness and attribution.
      The results are compared with the previous literature, and it is suggested that
      insight deficits in schizophrenia may vary depending on factors such as course
      and phase of illness.

PMID- 9783346
TI  - A multimethod approach to assessing perseverations in schizophrenia patients.
AB  - Perseverations have been associated with frontal lobe impairment and are often
      observed among schizophrenia patients. We assessed perseverations in
      schizophrenia patients (N = 71) using the Wisconsin Card Sorting Test (WCST) and
      a new Rorschach perseveration scale which yields three perseveration scores. We
      also compared the results of the schizophrenia patients with those of a normal
      comparison group (N = 71). We found that schizophrenia patients demonstrated a
      high number of perseverations on both the WCST and the Rorschach perseveration
      scale when compared to the normal comparison subjects. Among schizophrenia
      patients, WCST perseverative responses were significantly correlated with
      Rorschach-derived stuck-in-set perseverations, WAIS-R Vocabulary scores and
      negative symptom ratings. No significant differences in any of the measures of
      perseveration were found to be associated with diagnostic subtype. Finally, WCST
      and Rorschach measures for the schizophrenia and normal comparison participants
      were entered into a logistic regression. The WCST total errors and the three
      Rorschach perseveration measures resulted in the correct classification of 89.4%
      of the total cases, with a sensitivity of 91%, specificity of 91% and positive
      predictive power of 87.8%. These data provide evidence that perseverative
      behavior is widely observed in schizophrenia patients using a variety of
      instruments. The authors discuss the benefit of using multiple measures of
      perseveration in schizophrenia research.

PMID- 9783347
TI  - Backward masking in schizophrenia: time course of visual processing deficits
      during task performance.
AB  - Backward masking deficits have been put forward as potential psychological
      markers for vulnerability to schizophrenia. This study was conducted to
      investigate whether schizophrenic patients improve their performance on a
      backward masking task during a single test session. The ability of a degraded
      stimulus version of the masking task to act as a specific diagnostic marker for
      paranoid schizophrenia (versus affective disorder) was also investigated. The
      backward masking task was performed on 18 paranoid schizophrenic patients, 18
      unipolar depressed patients, and 18 non-psychiatric controls. Paranoid
      schizophrenic patients were included because they tend to show normal performance
      with traditional masking protocols. Schizophrenic patients made significantly
      more detection errors compared to depressives and non-psychiatric controls where
      interstimulus intervals (ISIs) longer than 14 ms were used. Unlike depressed
      patients and non-psychiatric controls, schizophrenic patients showed no reduction
      in error rate during the entire period over which the backward masking task was
      performed. The constant error rate which was observed at an ISI of 114 ms
      suggests that schizophrenic patients cannot attenuate the disruption effect due
      to deflection of attention from the target to the mask. The backward masking
      deficit in schizophrenia appears to arise from a temporarily stable visual
      processing impairment in performance within a single test session.

PMID- 9783348
TI  - Blunted cortisol response to a psychosocial stressor in schizophrenia.
AB  - Schizophrenia is considered a neurodevelopmental disorder in which vulnerability
      to stress may be a contributing factor. Coping is an important psychological
      component of stress processing, and the hypothalamic-pituitary-adrenal system
      (HPA system) is one of the biological components of stress adaptation.
      Disturbances of either of these components may make schizophrenic patients more
      vulnerable to develop a psychosis under stressful circumstances. In this study,
      10 schizophrenic men were compared with 10 healthy male controls in their
      response to a psychosocial stressor, consisting of a public-speaking task. Heart
      rate was monitored as a measure of autonomic arousal. HPA responses were assessed
      by measuring salivary cortisol. Coping skills were measured by using the Utrecht
      Coping List and the Ways of Coping Checklist. The stress of speaking in public
      increased the heart rate in both patients and controls; however, a significant
      cortisol response was found in the controls, but not in the schizophrenic
      patients. The patients used more passive and avoidant coping strategies than
      controls. The findings provide support for the notion that schizophrenic patients
      have an impaired ability to adapt, both psychologically and biologically, to
      their environment.

PMID- 9783349
TI  - Olanzapine response in treatment-refractory schizophrenic patients with a history
      of substance abuse.
AB  - As many as half of all schizophrenic patients have abused alcohol or illicit
      drugs. This study determines the extent of substance abuse in a treatment
      resistant population and assesses the response of this population to olanzapine
      treatment. Sixty patients with a DSM-III-R diagnosis of schizophrenia were
      included in an open 7-week trial of up to 25 mg/day of olanzapine. A history of
      substance abuse was present in 23 (38%) of the patients. At baseline evaluation,
      patients with a history of substance abuse had lower CGI scores and less negative
      symptomatology while having a higher rate of tardive dyskinesia. The overall
      group improved significantly over time. There were no differences in response
      between the substance-abusing (SA) and non-substance-abusing (NSA) patients as
      measured by the total BPRS, GGI and SANS ratings. The NSA group had significantly
      greater improvement in negative symptoms as measured by the BPRS negative symptom
      factor. Sixty-nine per cent (16/23) of the SA group and 60% (22/37) of the NSA
      were considered olanzapine responders by a priori criteria (p = NS).
      Extrapyramidal symptoms declined significantly in the overall group, but did not
      significantly differ between the SA and NSA groups. Treatment-refractory patients
      with prior substance abuse had a comparable outcome on olanzapine therapy to
      those with no history of abuse, as well as no increase in adverse effects. This
      suggests that olanzapine may be of benefit to SA patients who have a greater
      tendency for antipsychotic side effects and tardive dyskinesia.

PMID- 9783350
TI  - A comparative study of sertraline versus imipramine in postpsychotic depressive
      disorder of schizophrenia.
AB  - The objective of this study was to compare the efficacy and reliability of
      sertraline versus imipramine in the treatment of postpsychotic depressive
      disorder of schizophrenia. The diagnosis was based on DSM-IV research criteria.
      The Sympson-Angus Scale and SANS were performed in order to discriminate between
      depressive symptoms, the extrapyramidal side-effects of neuroleptics and the
      negative symptoms of schizophrenia. A 10-day placebo treatment period was applied
      to eliminate the possible influence of the placebo effect. The degree of severity
      of depression was determined using the Hamilton Depression Scale and the Clinical
      Global Impression Scale. The patients were randomly divided into two subgroups,
      each consisting of 20 people, who were given either 50 mg/day sertraline or 150
      mg/day imipramine, and their progress was followed for 5 weeks. The diagnosis and
      treatment results were evaluated using the double-blind method. In conclusion,
      although both drugs were found to be effective, sertraline was found to be more
      advantageous than imipramine in terms of rapid onset of action; frequency,
      severity and duration of side-effects, and relapse risk of schizophrenia.

PMID- 9783351
TI  - Differential prevalence of cigarette smoking in patients with schizophrenic vs
      mood disorders.
AB  - Rates of substance-use disorders among psychiatric patients are consistently
      higher than in the general population, yet there is no clear specificity to the
      relationship between types of substance use and psychiatric diagnoses. Cigarette
      smoking may represent a substance-use behavior which has greater specificity for
      major psychiatric diagnoses. We examined the self-reported history of cigarette
      smoking vs marijuana, alcohol and cocaine use among 83 male veteran psychiatric
      patients with primary mood (major depression or bipolar disorder; n = 20) or
      schizophrenic (schizophrenia or schizoaffective; n = 63) disorders. Those in the
      SCZ group compared to those in the AFF group were more likely to be ever-smokers
      (OR 8.5, 95% CI [2.2, 32.3]), and current smokers (OR 12.0%, 95% CI [3.6, 40]),
      independent of age differences between the groups. There were no significant
      differences in marijuana, alcohol or cocaine use between the two groups when age
      differences were controlled. Generalizability of the findings is limited by small
      number of subjects, male gender and veteran status; however, the significantly
      higher prevalence of smoking among individuals with schizophrenic disorders may
      support the growing evidence of linkages between the effects of nicotine and the
      neurobiology of schizophrenia.

PMID- 9783352
TI  - Bone age in adolescents with schizophrenia and obsessive-compulsive disorder.
AB  - The bone age (BA), height and weight of 20 adolescents with schizophrenia and 21
      matched adolescents with obsessive-compulsive disorder (COD) were measured. The
      BA of the schizophrenic patients was significantly higher than their
      chronological age (CA)(p < 0.05), while the OCD subjects' BA was non
      significantly lower than their CA. In addition, the difference between CA and BA
      (delta ages) in the schizophrenic adolescents was significantly different from
      the delta ages of the OCD adolescents (p , 0.05). Gender did not significantly
      affect BA or delta ages. A positive correlation (r = 0.5, p < 0.01) was obtained
      between CA and delta ages in the schizophrenic patients but not in the OCD
      patients. Both groups were within the normal range of weight and height
      percentiles.

PMID- 9783353
TI  - Factors confounding studies of circulating soluble interleukin-2 receptor levels
      in schizophrenia.

PMID- 9783354
TI  - [Lactose in human nutrition].
AB  - The disaccharide lactose is naturally present as a component of foods in milk and
      dairy products. In the gastrointestinal tract, lactose is hydrolysed by the
      enzyme beta-galactosidase (lactase) into glucose and galactose. These components
      are absorbed. In most people lactase activity decreases at the age of
      approximately 2 years of age. After this lactose intake can cause symptoms of
      bloating, flatulence, abdominal pain and diarrhoea due to the lactose reaching
      the large intestine. This phenomenon is called lactose intolerance. It is
      generally recommended that these people abandon the consumption of milk and dairy
      products. However, most lactose-intolerant people are able to digest small
      amounts of milk (approximately 200 ml). They can also consume cheese without
      (hard and semi-hard cheese) or only low lactose content (only present in 10% of
      soft cheese). These products are a very important source of calcium.

PMID- 9783355
TI  - [Mesh-plug operation: a simple, rapid and complication-free technique for
      managing inguinal hernia].
AB  - INTRODUCTION: The optimal inguinal hernia repair technique is a matter of debate.
      The Shouldice operation has long been regarded as the gold standard. While
      specialized hernia clinics have reproduced good results, a recurrence rate for
      trainees and non-specialized surgeons of between 10% and 15% seems to be more
      common. Laparoscopic hernia surgery has brought decreasing postoperative
      morbidity, low post-operative disability and early return to work. These
      advantages of a tension-free technique are due to the use of a prosthetic mesh.
      It is largely the efforts of Gilbert, Lichtenstein and Rutkow/Robbins which have
      popularized the use of prosthetic mesh by an open anterior approach in the USA.
      METHODS: Since January 1997 we have prospectively evaluated the open mesh plug
      repair described by Rutkow/Robbins in Basel and Lugano. We have operated on 110
      patients (103 male, 7 female). All patients were interviewed 4 weeks
      postoperatively at our clinic. RESULTS: There were no major complications. Two
      patients underwent reoperation for drainage of a haematoma. There was no early
      recurrence or infection. After 4 weeks 82% of all patients were back to normal
      activity. An early return to work has been noted (10 days on average for
      sedentary workers). CONCLUSION: The main advantages of this technique are
      simplicity, low cost, reduced post-operative disability and early return to work.
      It is much too early to say anything concerning recurrence in this series.

PMID- 9783356
TI  - [Surgical pain therapy in inoperable metastatic epigastric tumor by bilateral
      thoracoscopic splanchnicectomy].
AB  - Patients with unresectable supramesenteric malignancies often suffer from
      intractable pain. The supramesenteric viscera are supplied by the greater
      splanchnic nerve. Surgical options to effectively denervate the supramesenteric
      area are coeliac ganglionectomy, open or percutaneous coeliac ganglion block or
      transhiatal bilateral splanchnicotomy. The surgical minimally invasive
      alternative is thoracoscopic splanchnicectomy. In 7 patients pain was scored on a
      scale from 1 (no pain) to 10 (maximal pain) before and after surgery and weekly
      thereafter. Five bilateral and 2 left-sided thoracoscopic splanchnicectomies were
      performed. Operation time was 17 +/- 3 min for each side. The mean pain score
      dropped from preoperatively (under morphine sulphate medication) 7.4 +/- 0.6 to
      4.9 (2.5-8.25) 1 week postoperatively (p = 0.02) and to 4.9 (2.5-6.75) 7 weeks
      postoperatively (p = 0.02). The relief from back pain was immediate and complete,
      but abdominal pain tended to recur. Six of our 7 patients and their general
      practitioners rated the intervention as a success. Thoracoscopic splanchnicectomy
      affords excellent palliation in patients with unresectable supramesenteric
      tumour, offering reliable pain control.

PMID- 9783357
TI  - [Muscle metastasis as initial manifestation of adenocarcinoma of the stomach].
AB  - BACKGROUND: The presentation of gastric carcinoma with a metastasis in skeletal
      muscle is a distinct rarity. CASE REPORT: In a 72-year-old male patient a soft
      tissue mass behind the knee was biopsied rather late. Histology showed a
      metastasis of adenocarcinoma. The patient mentioned a slight feeling of
      strangulation, which led to endoscopy and the diagnosis of gastric carcinoma.
      Palliative chemotherapy was initially successful but the patient died after 21
      months. DISCUSSION: Based on this case history, three points are discussed: how
      to biopsy a peripheral soft tissue mass, how to proceed when a metastasis of an
      unknown primary tumor is diagnosed, and the epidemiology of metastases to
      skeletal muscle.

PMID- 9783358
TI  - [Milker's nodes].

PMID- 9783359
TI  - [Etiology and therapy of obstructive respiratory tract diseases in infancy and
      early childhood].
AB  - Wheezing disorders in early childhood are frequent, nevertheless little is known
      about their heterogeneous aetiology. In the last few years there has been
      increasing evidence of antenatal as well as postnatal influences which can make
      infants more prone to wheezing episodes. This review tries to classify various
      groups of wheezing disorders based on risk factors such as allergy, developmental
      differences in airway mechanics or association with viral infections. On this
      basis the different therapeutic regimens and particularly the effect of anti
      inflammatory treatment with inhaled corticosteroids in this age group are
      discussed. New concepts of anti-inflammatory treatment for croup syndromes are
      summarised.

PMID- 9783360
TI  - [Respiratory syncytial virus infection in childhood].
AB  - Respiratory syncytial virus is the most frequent cause of respiratory tract
      infections in infants and is responsible for annual winter epidemics of acute
      bronchiolitis. Over the last decades medical therapy has remained unchanged and
      controversial, despite intensive research. Inhaled bronchodilators are often not
      effective and should be discontinued if no beneficial response can be documented.
      Steroids and ribavirin are not indicated in previously healthy infants with acute
      RSV bronchiolitis. There is some evidence, however, that certain risk groups may
      benefit from their use. With good supportive care the mortality from RSV
      infection is now low. Postinfectious alterations in lung function are usually
      transient and reversible. High-risk infants can be protected from severe RSV
      infections by monthly infusions of RSV immune globulins. This treatment modality
      has, however, not gained wide acceptance because of the benign nature of the
      disease and the high costs and side effects of regular immune globulin infusions.
      An international consensus statement on the treatment of RSV bronchiolitis may
      help to reduce the wide differences in clinical practice.

PMID- 9783361
TI  - [Lung diseases in HIV-infected children].
AB  - Pulmonary diseases, including opportunistic and bacterial infections,
      lymphoproliferative disorders, and neoplasia, substantially contribute to
      morbidity and mortality in HIV-infected children. Current treatment modalities
      are largely successful and thus justify invasive aetiological diagnostic
      procedures.

PMID- 9783362
TI  - [Rare cause of acute thoracic pain: simultaneous occurrence of spontaneous
      pneumomediastinum and pneumopericarditis].

PMID- 9783363
TI  - [The heterogeneity of the myocardial mitochondrial apparatus and the mechanisms
      of its formation in the early ontogeny of rats].
AB  - The quantitative morphological characteristics of three types of mitochondria in
      adult rat cardiac myocytes are presented. The existence of two mitochondrial
      functional modes depending on the intracellular localization and condition of the
      myofibrillar apparatus has been revealed. The quantitative correlation between
      the types of these organelles during ontogenesis has been estimated.

PMID- 9783364
TI  - [The interrelations between karyotypic stability and interchromosomal
      associations in mammalian cells].
AB  - The interchromosome associations between heterologous chromosomes (for the type
      of Robertsonian translocations); frequencies of the association between
      individual chromosomes (identified by G-bands) and mouse line pecularities, the
      directions of cytodifferentiation, the stages of cell neoplastic transformation
      in cell populations of various origin have been estimated. The presence of
      interrelations between individual chromosome associations and genetic and
      cytological cell characteristics with the use of different mathematical methods
      of analysis has been revealed.

PMID- 9783365
TI  - [Chromosome substitution and genotype adaptation in Drosophila melanogaster].
AB  - The subject of research was the relative adaptability and some of its components
      (fertility, heat resistance, longevity under the normal conditions and under the
      conditions of starvation) of the line flies D. melanogaster (C-S, cn, vg) and
      derived forms received in the result of reciprocal substitution of chromosomes 1,
      2 and 3. The experiments performed, showed that the intrusion of the alien
      chromosomes into the karyotype of analysed line flies caused the decline in
      adaptability index in the most variants of experiment.

PMID- 9783367
TI  - [The blood groups of bulls as genetic markers of sperm quality].
AB  - The research results are presented concerning the relation between blood groups
      of bulls and quantitative and qualitative indices of sperm. The allele markers of
      high, low various as well as the indifferent ones have been identified for each
      index. The results of the research confirm the possibility of valuation and
      prognostication of bull sperm quality according to the blood groups alleles and
      genotypes.

PMID- 9783366
TI  - [The cytofluorimetric analysis of the nuclei in the regenerating rat liver in the
      late periods after x-ray irradiation].
AB  - The flow cytofluorimetric method allowed to show that intact liver nucleus
      population of adult (6 months) rats consists of discrete ploidy classes (2c, 4c,
      8c and 16c+), from which the diploid class was approximately a half of the total
      nuclei. Thirty days after the wholebody X-ray irradiation with a dose of 2 Gy,
      the percentage frequency of each nuclear class was statistically unchanged.
      However, the polyploidization level of the total nuclear population increased.
      Partial hepatectomy induces an entering into mitotic cycle (maximum S-phase; 22 h
      after operation) of the most of the hepatocyte nuclei in both irradiated and
      unirradiated animals. With that the relative number of nuclei in S-phase
      decreases in geometric progression according to increasing of ploidy class. In
      regenerating liver of irradiated rats in comparison with that of unirradiated
      ones, the greater part of nuclei enters into the mitotic cycle at the expense of
      di- and especially tetraploid nuclei.

PMID- 9783368
TI  - [The content of DNA in the oral mucosal epitheliocytes and the expression of
      oncofetal antigens on the peripheral blood T-lymphocytes of women with breast
      dysplasias].
AB  - The DNA content in epitheliocytes of the mucous membrane of the oral cavity and
      expression of carcinoembryonic antigen and trophoblast-specific beta-1
      glycoprotein on peripheral blood lymphocytes, peripheral blood T-lymphocytes
      subsets into three groups of patients: 1--diffusion mastopathy; 2--diffusion
      mastopathy with fibromyoma uteri and 3--fibroadenoma were studied. It was
      indicated that DNA content was higher in all groups in comparison with healthy
      women and it was shown that in contrast to healthy women, 45% of patients studied
      had abnormal rate of T-cells subsets, about 30% of them had abnormal expression
      of CEA and TSG on peripheral blood lymphocytes. The data obtained show the
      significant disbalance in the mechanisms of defence and compensation taking place
      in the organisms of patients with nonmalignant mammary diseases.

PMID- 9783369
TI  - [The variability and heritability of the indices of speed and exterior characters
      in horses of the Orlov trotter breed].
AB  - Study of the variability and heritability of sprightliness and exterior
      characteristics which are the constituent factors of capacity for work of
      trotting horse breed, permits predicting and planning the direction of selection
      work in the breed, and determining the efficiency of animals selection according
      to phenotype. To increase the level of capacity for work of Orloff trotting horse
      breed, according to the paper data, more consideration should be given to
      correctness of the exterior, as a biomechanical basis of the horse motion.

PMID- 9783370
TI  - [The genetic polymorphism of somatotropin].
AB  - This review deals with the growth hormone genetic polymorphism and presents
      information about somatotropin variants, which are synthesized in the pituitary
      gland and in the placenta. The detailed results of somatotropin DNA polymorphism
      study in different animal species are presented. It is supposed that some DNA
      alleles which find their source in replacements in non-coding part of the gene,
      express their phenotype by the deviations in the expression control. The
      polymorphous somatotropin genetic system may be used as the marker system in the
      QTL study.

PMID- 9783371
TI  - [Prenatal diagnosis and therapy of feto-fetal transfusion syndrome].
AB  - Twin-twin transfusion syndrome (TTTS) is a serious complication of monochorionic
      twin pregnancies. It is the result of an unbalanced transfusion of blood across
      placental vascular anastomoses. TTTS appears predominantly in the second
      trimester of pregnancy characterized by discordance of growth as well as
      polyhydramnios in the recipient and oligo-/anhydramnios in the donor. Prenatal
      diagnosis is possible by non-invasive and invasive methods. The prognosis of the
      untreated TTTS is very poor. Serial amniocenteses and laser therapy are used
      resulting in survival rates of about 60%. Intrauterine death of one twin is
      associated with a high risk of morbidity in the surviving twin. Monochroionic
      twins have to be identified in early pregnancy. Close surveillance is necessary
      to diagnose TTTS at an early stage of the disease.

PMID- 9783372
TI  - [Inducing labor with intracervical prostaglandin (PG) gel administration. A
      comparative analysis of 171 patients with 2 different preparations of PGE2 with
      regard to course of labor and fetal outcome].
AB  - In the present study we examined whether the difference in viscosity of two
      prostaglandins applied intracervically for induction of labour influences course
      of labour and fetal outcome. A comparative analysis was carried out in 171
      patients, which received either Cerviprost (n = 85) or Prepidil (n = 86) at 6
      hour intervals. The results show that the viscosity of the PG E2 has no influence
      on the course of induction of labour, the mode of delivery or on fetal outcome.
      The low viscosity does also not present an increased risk for uterine
      overstimulation, even in case of intracervical application.

PMID- 9783373
TI  - [Significance of myoma-induced complications in pregnancy. A comparative analysis
      of pregnancy course with and without myoma involvement].
AB  - In the present study we analyzed the relation between complications in pregnancy-
      fetal growth retardation, premature rupture of membranes, preterm labour,
      abruptio placentae, mode of delivery, puerperium--and the size, number and
      location of myomas. A retrospective comparison was performed in 474 patients (94
      pregnant women with myoma and 380 with a normal uterus as controls). The course
      of pregnancy, the mode of delivery and the puerperium were examined. The study
      showed that retroplacental submucous myomas increase the risk of fetal growth
      retardation (14% vs. 6.6%) and abruptio placentae (3.2% vs. 1.3%). The size of
      the myomas was not relevant. A caesarean section, especially for fetal
      malpresentation, was also more frequent in patients with submucous myoma (52.9%
      vs. 27.9%). There was no difference, however, in the postpartal course between
      the submucous myoma group and the controls, respectively. Subserous or intramural
      fibroids had no influence on the course of pregnancy, the mode of delivery or the
      postpartal period.

PMID- 9783374
TI  - [Incidence of typical nephrocalcinosis ultrasound findings in premature infants
      during enteral calcium and phosphate administration].
AB  - Supplementation of calcium and phosphate is recommended in nutrition of low birth
      weight infants to ensure a physiological development of postnatal bone
      mineralisation. To investigate whether high dose calcium supplementation
      increases the risk of renal calcification in preterm infants, serial ultrasound
      examinations were performed in 30 preterm infants (gestational age 29.5 (26-35)
      weeks; birth weight 1382 (610-2010) g) before, during and after oral calcium and
      phosphate supplementation. Total calcium input was on average 3.1 mmol/kg/d,
      total phosphate input on average 2.1 mmol/kg/d). All children showed normal
      kidney ultrasound before entering the study. During mineral supplementation three
      children developed hyperechoic renal medullary pyramids, the typical ultrasound
      pattern of nephrocalcinosis. Supplementation was stopped immediately and
      pathologic ultrasound patterns disappeared in all 3 children.

PMID- 9783375
TI  - [Intravenous immunoglobulins (IVIG) in treatment of an antiphospholipid syndrome
      in pregnancy].
AB  - A patient with a history of early onset preeclampsia and repeated fetal death,
      high titer IgG anticardiolopin antibodies and prolonged aPTT was treated during
      her third pregnancy with intravenous immunoglobulins (IVIG) from the seventh
      month of pregnancy onwards. Every month--after a loading dose of 30 g
      immunoglobulins--a daily infusion of 3 g immunoglobulin was for three days was
      given during six consecutive cycles. The patients pregnancy ended preterm with a
      life birth, delivered by cesarean section, because of a severe preeclampsia. The
      1600 g weighing boy was in good health. Each treatment with IVIG resulted in a
      reduction of anticardiolipin-antibodies. During the seventh months observation
      period, a gradual increase in PAI activity/factor VIIIR:Ag was found. A partial
      transient reduction of antiphospholipid-antibody levels was observed immediately
      following each treatment course resulting in an accelerated fetal outcome.

PMID- 9783377
TI  - [Cytokine concentrations and expression of adhesion molecules in the lower
      uterine segment during parturition at term: relation to cervical dilatation and
      duration of labor].
AB  - OBJECTIVE: To determine the concentrations of tumor necrosis factor (TNF)alpha,
      interleukin (IL)beta, IL-6 and IL-8 and the expression of endothelial leukocyte
      adhesion molecule-1 (ELAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in
      the lower uterine segment during parturition at term and to investigate
      correlations with the stage of cervical dilatation and with the duration of
      labor. PATIENTS AND METHODS: Biopsy specimens were taken from the lower uterine
      segment of 59 women undergoing non-elective cesarean sectin at term at different
      stages of cervical dilatation (< 2 cm, n = 17; 2-3 cm, n = 12; 4-6 cm, n = 13; >
      6 cm, n = 17) after varying length of the time in labor (1-6 h, n = 18; > 6-12 h,
      n = 16; > 12-24 h, n = 15; > 24 h, n = 10). The concentrations of TNF alpha, IL-1
      beta, IL-6 and IL-8 in protein extracts of these specimens were determined by
      enzyme linked immunosorbent assays and the expression of ELAM-1 and VCAM-1 was
      studied by immunohistochemistry. Staining was considered negative if < 5% of the
      endothelial cells were stained and positive if > or = 5% were stained. RESULTS:
      At < 2 cm dilated cervix the median concentrations of TNF alpha, IL-1 beta, IL-6
      and IL-8 were 8.0 pg/mg total protein (TP), 1.3 pg/mg TP, 12.6 pg/mg TP and 17.2
      pg/mg TP, respectively. At 4-6 cm dilatation the median concentrations were
      increased (TNF alpha: 22.2 pg/mg TP [P = 0.05], IL-1 beta: 22.2 pg/mg TP [P <
      0.05], IL-6: 1226 pg/mg TP [P < 0.05], IL-8: 2081 mg/mg TP [P < 0.05]). At > 6 cm
      dilatation no further increase was observed. The expression of ELAM-1 and VCAM-1
      was significantly greater at > 6 cm dilatation than < 2 cm dilatation (P < 0.001
      and 0.05, respectively). With increasing duration of labor, the concentrations of
      IL-1 beta, IL-6 and IL-8 (but not of TNF alpha) increased and were significantly
      higher at > 6 cm dilatation than at < 2 cm (P < 0.05). Expression of ELAM-1 and
      VCAM-1 did not vary with duration of labor. CONCLUSIONS: These first
      investigations of cytokines and cell adhesion molecules in the lower uterine
      segment at both different stages of cervical dilatation and different duration of
      labor support the decisive role of cytokines for normal cervical dilatation.
      Local changes in the lower uterine segment independent from the effects of labor
      (e.g. increase of endothelial adhesivity) seem to be of special importance in
      this process.

PMID- 9783376
TI  - [Nitroglycerin for intraoperative uterus relaxation in cesarean section. Results
      of a randomized clinical study].
AB  - Between June 1994 and July 1996, a prospective, randomized, double-blind clinical
      study was carried out on 97 patients scheduled for elective cesarean section
      under general anesthesia at the gynecology departments of the Virchow and Charite
      Hospitals (both university hospitals of the Humboldt University, Berlin) in order
      to test the efficacy of glycerol nitrate (GTN: syn.: nitroglycerin) as an
      intraoperative short-acting tocolytic agent to ease fetal extraction in cesarean
      section in comparison to a placebo. At the time of the uterine puncture incision,
      either 0.25 mg (n = 32 patients) or 0.5 mg (n = 34) of GTN or physiological
      saline (n = 31) was administered as an intravenous bolus. Maternal and fetal
      pulse rates and blood pressures were closely monitored. The authors developed a
      scale to evaluate the degree of decrease in uterine tone and the ease of fetal
      extraction. The statistical evaluation of these estimations revealed no
      significant easing of fetal extraction and no significant increase in the
      reduction of uterine tone after administration of both GTN dosages in comparison
      to the administration of placebo (p > 0.01). Easing of fetal extraction cannot be
      achieved with the administration of 0.25 or 0.5 mg GTN, at least not in elective
      cesarean sections of greater than 34 weeks of gestation.

PMID- 9783378
TI  - [Obstetrical-neonatal emergency: shoulder dystocia].

PMID- 9783379
TI  - [Neonatal lupus erythematosus].

PMID- 9783380
TI  - [Study of molecular-kinetic properties and characteristics of the activation of
      glycogen phosphorylase b from skeletal muscles of the frog Rana temporaria].

PMID- 9783381
TI  - [Inhibition of Na, K-adenosine triphosphatase by glutamate in cerebral cortex
      synaptosomes. Protective effect of alpha-tocopherol and superoxide dismutase].

PMID- 9783382
TI  - [Effect of mildronate on the rate of lipid peroxidation and their fatty acid
      composition in the fetal brain and placenta of the rabbit Oryctolagus cuniculus].

PMID- 9783383
TI  - [Properties of soluble and membrane intestinal hydrolases in Macaca rhesus
      monkeys].

PMID- 9783384
TI  - [Study on the ability to identify plane and three-dimensional objects in
      chimpanzee].

PMID- 9783385
TI  - [Structure of receptor organs of the vestibule and animal behavior during
      weightlessness].

PMID- 9783386
TI  - [Membrane and soluble forms of disaccharidases from rat small intestine during
      ontogenesis].

PMID- 9783387
TI  - [The population dynamics of Salmonella typhi and Tetrahymena pyriformis during
      joint cultivation].
AB  - The data on changes in the number, as well as cultural and biological properties
      of S. typhi and free-living T. pyriformis in the course of their joint
      cultivation at 2 degrees C and 25 degrees C are presented. As suggested on the
      basis of the results of this experiment, the interaction of S. typhi with T.
      pyriformis may facilitate the preservation of the bacteria in the environment and
      be a stage in their migration along trophic chains.

PMID- 9783388
TI  - [The effect of the pH of the medium on induced autolysis in populations of
      enterobacteria].
AB  - Changes in pH in the process of the induced autolysis of salmonellae and
      Escherichia coli were studied. The induced autolysis of enterobacterial
      populations was studied in connection with the acidity values of the medium in
      which the process was carried out. The pH of extracellular fluid, the optical
      density of cell suspension, the content of total protein and amino nitrogen were
      analyzed. Enterobacterial populations were found to be capable of the self
      regulation of the acidity of the medium in the process of induced autolysis. The
      study revealed that the most Intensive autolysis of bacteria took place when the
      process was carried out in extreme alkaline values of pH.

PMID- 9783389
TI  - [A monoclonal antibody-based study of the antigenic interrelations of typical and
      R forms of Vibrio cholerae].
AB  - Monoclonal antibodies to surface determinants of V. cholerae R forms (R-McA) were
      obtained. R-McA and monoclonal antibodies to lipopolysaccharide (LPS) of V.
      cholerae S forms (S-McA) were used to show that the LPS of deeply altered
      vibrios, agglutinating only with RO serum, completely lost its O-side chain. Some
      common O determinants on the basis of S-McA were detected in typical cultures of
      V. cholerae O1 and RO vibrios which agglutinated to 1/4 T with O serum and, in
      low titers, with RO serum. V. cholerae O1 were not capable of specifically
      binding with R-McA. Not all R strains under study were identified with the use of
      available R-McA due to essential differences of their terminal monosaccharides
      responsible for serological specificity.

PMID- 9783390
TI  - [The corrective action of antibodies in experimental intestinal dysbacteriosis].
AB  - As shown in this work, antisera obtained after the immunization of animals with
      vaccines, prepared from Salmonella minnesota strain R595 (Re mutant) or
      Escherichia coli O14 having enterobacterial common antigen (ECA), as well as
      human antisera with elevated titers of antibodies to Re glycolipid or to LPS O14
      (ECA), inhibited the development of experimental intestinal dysbacteriosis in
      white mice, induced by the administration of ampyox in large doses. The degree of
      the inhibiting action of the antisera was proportional to antibody titers, which
      was indicative of the fact that antibodies possibly played some role in the
      regulation of the amount of intestinal microflora.

PMID- 9783391
TI  - [Antiendotoxin immunity in experimental intestinal dysbacteriosis in mice].
AB  - The development of intestinal dysbacteriosis in white mice, caused by the
      administration of ampyox in large doses, was shown to be accompanied by a
      considerable decrease in cell-mediated and humoral antiendotoxin immunity, which
      was manifested by a decrease in the titers of antiendotoxin antibodies and in the
      content of polymorphonuclear leukocytes, capable of binding endotoxin.

PMID- 9783392
TI  - [An additional dehydrogenase or oxidation-reduction test in the classification of
      enterobacteria].
AB  - The dehydrogenase (DHG) or oxidation-reduction test is proposed for use together
      with the determination of such enzymes as hydrolases, cytochrome oxidase,
      dehydrocarboxylase, urease, etc. 200 Citrobacter freundii cultures and 76 strains
      of enteropathogenic Escherichia (EPE) were studied with the determination of
      their DHG activity in semiliquid mannitol and in Kligler's medium. The study
      revealed that this test, characterized by the reduction of the indicator,
      similarly to that in salmonellae and shigellae, was constantly negative in
      semiliquid mannitol in C. freundii and in 97.3% of cases in EPE. In 17.5% of C.
      freundii lactose-positive cultures the DHG test in Kligler's medium was positive,
      which made it possible to regard them as a separate biovar. Taking into account
      the results of this investigation, the subdivision of C. freundii into 3 biovars
      is proposed.

PMID- 9783393
TI  - [The design and study of an ogt deletion mutant of Salmonella typhi].
AB  - The chromosome of S. typhi, similarly to those of Escherichia coli and Salmonella
      typhimurium, was found to contain ogt gene. Using Cmr gene, flanked by the
      corresponding sites of Salmonella chromosome, we managed to create S. typhi ogt
      deletion mutant strain. As shown in this study, ogt gene, together with giving
      protection against alkylating, methylating, ethylating and propylating agents,
      played an important role in protection against other mutagenic factors. In
      contrast to the wild strain, S. typhi ogt deletion mutant strain was found to be
      sensitive to UV radiation, pesticides and antimicrobial preparations.

PMID- 9783394
TI  - [The persistent characteristics of Listeria monocytogenes isolated from different
      sources].
AB  - A number of biological properties of L. monocytogenes was studied. Significant
      differences in the lysozyme, "anti-interferon", RNAase and lipase activity
      between strains isolated from different warm-blooded animals and from
      environmental objects were shown. 75% of all strains under study were found to
      have "anti-interferon" activity, while no antilysozyme activity was detected.

PMID- 9783395
TI  - [The theoretical bases of the epidemiology of viral hepatitis B].
AB  - In this article the development of the concepts concerning the sources of
      hepatitis B virus in the second half of the XXth century is analyzed and the
      importance of patients with manifest and latent forms of chronic infection as the
      main reservoir of the infective agent is substantiated. The scheme of the
      mechanisms and paths of the transmission of hepatitis B virus is proposed, the
      mechanism of transmission understood only as the natural ways of the spread of
      the infective agent which result from its evolutionary development and can be
      only slightly controlled at present. The study revealed that the present decrease
      of morbidity rate is greatly determined by measures of the social character,
      aimed at the elimination of the artificial paths of virus transmission.

PMID- 9783396
TI  - [Hepatotropic delta-virus infection in children].
AB  - A high level of contamination with hepatitis delta virus (HDV) in central
      Kazakhstan was established. Infection mainly occurred in the process of common
      injections. The possibility of the horizontal and vertical spread of this
      infection was shown. Sharp distinctions in the course and outcomes of delta co-
      and superinfections in children were found. In most children superinfection was
      manifested by a severe course, and in almost all children by the development of
      chronic active hepatitis (CAH). The latter was characterized by pronounced
      clinical symptoms, prolonged relapsing course, infrequent stabilization (in one
      third of patients observed from the age of 7 to 12 years, the development of
      cirrhosis of the liver. The differences in the course of co- and superinfection
      may be explained by different relationships between hepatitis B virus and HDV in
      these forms of infection, and the prolonged unfavorable course of CAH may be
      regarded as a consequence of the appearance of profound and stable
      immunodeficiency.

PMID- 9783397
TI  - [Intrauterine zoonotic infections in Dagestan].
AB  - As the result of the prospective examination of 863 pregnant women in urban and
      rural consultation clinics for women in Daghestan, a high proportion of them were
      found to be infected with toxoplasmosis (25.5%), brucellosis (1.85%) and
      listeriosis (12.2%). The data on the contamination of 1325 women with aggravated
      obstetric history were confidently higher, constituting 52.0%, 3.3% and 22.2%
      respectively. The results of the examination of women working on live-stock farms
      (226 women) and poultry farms (106 women) demonstrated a significantly high
      frequency of contamination with the above-mentioned zoonotic infections. The data
      thus obtained were indicative of the necessity of organizing epidemiological
      surveillance on these infections; for their diagnostics a complex of laboratory
      methods could be used, though the effectiveness of these methods was different in
      different nosological forms.

PMID- 9783398
TI  - [The immunological efficacy of the combined vaccine Trimovax intended for the
      prevention of measles, mumps and rubella].
AB  - In 1996 the immunization of children against measles, mumps and rubella with
      combined vaccine Trimovax ("Pasteur Merieux Connaught", France) was carried out
      in the Republic of Belarus. The reactogenicity of the vaccine was studied in 372
      children. To evaluate immunological effectiveness, the sera of 324 children were
      used. Postvaccinal reactions of different intensity were registered in 5.6% of
      the children; of these, 1.3% exhibited severe reactions. Among the vaccinees,
      protective titers of antibodies to measles were found in 97.6% to mumps, in 93.8%
      and to rubella, in 96.0% of the children. Antibodies to all three components of
      the vaccine were present mainly in high and moderate titers. The results thus
      obtained indicate that, Trimovax was well tolerated and proved to be
      immunologically active.

PMID- 9783399
TI  - [The choice of the optimal schedules in the vaccination procedure against
      influenza in elderly subjects].
AB  - To improve the vaccinal prophylaxis of influenza, the comparative study of live
      trivalent influenza allantoic vaccine, dried, for adults, produced by the Irkutsk
      Enterprise for Immunological Preparations (Russia), and inactivated trivalent
      influenza split vaccine, obtained from Wyeth-Ayerst Company (USA), as well as
      schedules of their combined use for the vaccination of elderly persons, was
      carried out. The examination of 600 subjects revealed that the vaccines were well
      tolerated; the combined use of these two vaccines, as well as the use of the
      inactivated influenza vaccine (IIV) alone, ensured high immunogenic activity
      (60.0-80.0% of seroconversions). The live influenza vaccine (LIV) stimulated the
      production of specific antibodies only in 19.0-35.0% of the vaccinees; most of
      these vaccinees exhibited positive reaction only to one of the vaccine strains.
      Following the injection of LIV, the level of postvaccinal immunity was retained
      for at least 6 months. In the vaccinees receiving both vaccines the tendency
      towards a decrease in mean geometric titer values was less pronounced (0.2-0.4
      log2) than in those receiving only IIV (0.5-0.7 log2). At the period of the rise
      of influenza morbidity, the contamination rate in the vaccinees with the positive
      postvaccinal dynamics of antibodies was low (26.0%). The indices of effectiveness
      were 3.8 for combined vaccination, 3.5 for IIV and 2.6 for LIV. The schedule of
      vaccination with IIV with the possible revaccination LIV 3-4 weeks later was
      recommended.

PMID- 9783400
TI  - [An evaluation of the epidemiological and economic efficacy of immunizing adults
      with the Vaxigrippe vaccine].
AB  - The results of the evaluation of the epidemiological and economic efficiency of
      the immunization of the adult population with the vaccine Vaxigrip (Pasteur
      Merieux Connaught, France) are presented. In accordance with the results obtained
      in this investigation, this vaccine was found to have pronounced epidemiological
      (prophylactic) efficiency and to be well tolerated. To achieve a perceptible
      epidemiological effect, it was sufficient to cover 43% of the group with
      vaccination. The economic effect of the use of Vaxigrip exceeded the costs
      connected with carrying out vaccination sixfold.

PMID- 9783401
TI  - [The development and certification of the Hepabest anti-HBc IgG test system for
      detecting antibodies to the core antigen of the hepatitis B virus].
AB  - The comparison of the newly developed "HepaBest anti-HBc IgG" assay system for
      the detection of hepatitis B virus (HBV) core antigen with the reference system
      "ImmunoComb HBc IgG" (Orgenics, France-Israel) and its approbation on 91 serum
      samples from patients in the Infectious Clinical Hospital were carried out. The
      coincidence rate of the results obtained with the use of the two assay systems
      was 87.9%. The system "HepaBest anti-HBc IgG" permitted the detection of patients
      whose sera contained no other HBV markers, except anti-HBc IgG. This assay system
      may be recommended for use in clinical and epidemiological investigations for
      ascertaining the diagnosis.

PMID- 9783402
TI  - [An antigenic analysis and the protective properties of the R-form
      lipopolysaccharides of gram-negative bacteria].
AB  - The antigenic and immunogenic properties of the R-form lipopolysaccharides (R
      LPS) of Pseudomonas aeruginosa, Salmonella minnesota, Escherichia coli and
      Shigella were studied. The results of the study revealed the existence of
      antigenic relationship between P.aeruginosa R-LPS and R-LPS Escherichia and
      Shigella. In serological tests no antigenic relationship between P. aeruginosa R
      LPS and Salmonella R-LPS was revealed, but as shown in earlier experiments of the
      protection of mice, Re-glycolipid stimulated protective immunity against
      Pseudomonas infection in the animals. On the basis of R-LPS obtained from
      selected P. aeruginosa and Salmonella strains a vaccine was prepared which proved
      to be effective against infection caused by P. aeruginosa S-strain in experiments
      on mice. The vaccine induced protection in 40-100% of immunized mice, depending
      on the scheme of immunization. The vaccine may probably be effective against
      infections caused by other gram-negative bacteria.

PMID- 9783403
TI  - [Anti-RS viral IgE in respiratory syncytial viral infection in adult patients
      with a complicated course of bronchitis].
AB  - In adult patients with different variants of the complicated course of bronchitis
      (prolonged, relapsing, chronic) respiratory syncytial (RS) virus infections were
      shown to occur very frequently (37-72%, depending on the form on bronchitis). In
      220 cases of RS infection the content of anti-RS-virus IgE in the blood was
      analyzed. The reaction of specific IgE was more pronounced in RS infection
      observed in patients with acute of bronchitis, than in those with chronic forms.
      The occurrence of RS-virus infections and reinfections was shown to be directly
      related to the presence of the broncho-obstructive syndrome in patients. The
      direct correlation between high levels of serum anti-RS-virus IgE and the
      presence of bronchospasms in patients, revealed in this study, was indicative of
      the possible pathogenetic role of this immunoglobulin: the Pearson association
      factor (rA) was 0.32, p < 0.01. Depending on the specific features of the
      clinical course of bronchitis, differences in the dynamics and speed on immune
      response, in the duration of the preservation of anti-RS-virus IgE in the blood,
      as well as in the character of the reaction of this immunoglobulin to single and
      multiple RS-virus lesion, were observed.

PMID- 9783404
TI  - [The use of random amplification of polymorphous bacterial DNA for the typing of
      bacteria in the genus Citrobacter].
AB  - To obtain the profiles of randomly amplified DNA, isolated from bacteria of the
      genus Citrobacter, the method of polymerase chain reaction was used. Nine
      oligonucleotides were evaluated for the possibility of their use as primers for
      the amplification of random polymorphous sequences of DNA; of these, 2
      oligonucleotides which generated profiles, sufficiently reproducible and typical
      for different C. freundii and C. diversus strains, were selected. The possibility
      of using the above oligonucleotides in pair for amplification of species-specific
      fragments of polymorphous bacterial DNA for typing was shown.

PMID- 9783406
TI  - [The development of intestinal dysbacteriosis in newborn infants with a
      deficiency of antibodies to the Re-glycolipid].
AB  - The dependence of the quantitative content of Escherichia coli in the feces of
      newborn infants 3 days after birth on the titer of anti Re-glycolipid antibodies
      in umbilical blood and in mother milk was studied. The reverse correlation
      between the number of bacteria in feces and the titers of anti Re-glycolipid
      antibodies was established, the amount of bacteria depending more on antibody
      titers in umbilical blood than on those in mother milk. The conclusion was made
      that antiglycolipid antibodies played an important role in the regulation of the
      quantitative content of E. coli in the intestine of newborn infants. In case of
      the deficiency of such antibodies intestinal dysbacteriosis may develop in
      newborn infants.

PMID- 9783407
TI  - [The etiology of sporadic acute pneumonia in children].
AB  - The complex microbiological study of tracheobronchial washings and the detection
      of antibodies to surface components of whole bacterial cells in the indirect
      fluorescence test permitted the determination of the pneumococcal etiology of
      acute pneumonia (AP) in 134 children aged 1 month to 13 years (97.1%). In the
      course of AP 13 patients (9.4%) were found to have acute infectious processes
      caused by Haemophilus influenzae (5 cases), different enterobacteria (4 cases),
      Moraxella catarrhalis (2 cases), as well acute infectious destruction of the
      lungs and pyopneumothorax (1 case), whose etiological factors were Staphylococcus
      aureus and nontyping H. influenzae strains.

PMID- 9783405
TI  - [The principles of the combined therapy of intestinal dysbacteriosis].

PMID- 9783408
TI  - [The enzymatic activity of IgG preparations in viral hepatitis].
AB  - The activity of the enzymatic activity of the preparations of IgG1, IgG2 and
      IgG4, isolated from the blood of patients with acute virus hepatitis B and
      chronic viral hepatitis C resulting in cirrhosis, was studied. The blood samples
      were found to have DNAase activity significantly exceeding that of
      immunoglobulins isolated from the blood sera of healthy donors, as well as
      peroxidase, oxidase and esterase activities, whose level did not significantly
      differ from those of the donor blood sera. The interaction of IgG preparations
      with the cations of different metals was studied. The study revealed that the
      addition of CuSO4 solution at the final concentration of 4.7 x 10(-5) M to the
      blood samples led to a significant increase in activity in comparison with the
      initial one (on the average, 7.8 +/- 2.97 times) in all 14 samples. The activity
      thus observed was partially inhibited by the addition of the solution of
      staphylococcal protein A. As noted in the course of this study, high DNAase and
      peroxidase activities of Ig were most frequently observed in patients with
      cirrhosis of the liver. The difference in the levels of IgG activity between
      patients with cirrhosis of the liver and patients with virus hepatitis, but no
      signs of cirrhosis, is not significant.

PMID- 9783409
TI  - [The status of the immunity system in diphtheria].
AB  - The complex study of cell-mediated and humoral immunity characteristics, as well
      as nonspecific protective factors, in 30 diphtheria patients, 9 clinically
      healthy carriers and 54 healthy subjects was carried out. In healthy immunized
      subjects normal characteristics of all elements of immunity were observed in
      combination with high titers of antitoxins and sensitization of lymphocytes to
      diphtheria toxoid. In healthy carriers the presence of cell-mediated and humoral
      immunity to diphtheria was associated with disturbances of the metabolic activity
      of phagocytes and a decrease in the proliferation of lymphocytes in response to
      the mitogen. Diphtheria patients were found to have changes in all elements of
      immunity, especially pronounced in severe forms of the disease.

PMID- 9783410
TI  - [The mechanisms of the synergistic lethal action of enterobacterial
      lipopolysaccharide and staphylococcal enterotoxin type A].

PMID- 9783411
TI  - [The mechanisms of the anti-infective protection of the female reproductive
      tract].

PMID- 9783413
TI  - [Intestinal acidity as a protective factor in the host organism].

PMID- 9783412
TI  - [The prospects for improving chemical cholera vaccines].

PMID- 9783414
TI  - [The molecular epidemiology of diphtheria].

PMID- 9783415
TI  - [Nosocomial salmonellosis as an independent nosological form of human infectious
      pathology].

PMID- 9783416
TI  - [Salmonella infection in the surgical departments of a city hospital].

PMID- 9783418
TI  - [An epidemic outbreak of pseudotuberculosis in a boarding school].

PMID- 9783419
TI  - [An outbreak of acute intestinal infections in general education schools (2)].

PMID- 9783417
TI  - [An outbreak of acute intestinal infections in general education schools (1)].

PMID- 9783420
TI  - [Clinical microbiology and the outlook for its teaching].

PMID- 9783421
TI  - Na2[(mu-N,N'-C10H12N2O8)(mu-O)(mu-S)-Mo2O2].2H2O.
AB  - Analogs of bridging-oxo complexes of dimolybdenum(V) where sulfide replaces one
      or both bridges are known. After reduction of [(MoO3)2(mu-edta)]4- (edta is
      ethylenediaminetetraacetate) with dithionite at pH 6 in the absence of dioxygen,
      slow replacement of bridging oxide with sulfide produced in situ produces the
      title compound, disodium mu-(ethylenediaminetetraacetato)-mu-oxo-mu-sulfido
      bis[oxomolyb denum(V)] dihydrate, Na2-[Mo2O3S(C10H12N2O8)].2H2O. IR and NMR
      spectroscopic analyses are consistent with an unsymmetrical complex. In the
      molecular structure, the Mo centers have distorted octahedral coordination, with
      an average Mo-S distance of 2.320 (1) A and an average bridging Mo-O distance of
      1.938 (3) A. The Mo...Mo contact distance [2.666 (1) A] is intermediate between
      those in comparable di-mu-oxo and di-mu-sulfido complexes. The two Na+ ions have
      five and six nearest O atoms in their coordination spheres, which each include
      one disordered water oxygen.

PMID- 9783422
TI  - A review of the occurrence, toxicity, and biodegradation of condensed thiophenes
      found in petroleum.
AB  - Condensed thiophenes comprise a significant portion of the organosulfur compounds
      in petroleum and in other products from fossil fuels. Dibenzothiophene (DBT) has
      served as a model compound in biodegradation studies for over two decades.
      However, until quite recently, few other organosulfur compounds were studied, and
      their fates in petroleum-contaminated environments are largely unknown. This
      paper presents a review of the types of organosulfur compounds found in petroleum
      and summarizes the scant literature on toxicity studies with condensed
      thiophenes. Reports on the biodegradation of benzothiophene,
      alkylbenzothiophenes, DBT, alkylDBTs, and naphthothiophenes are reviewed with a
      focus on the identification of metabolites detected in laboratory cultures. In
      addition, recent reports on quantitative studies with DBT and naphtho[2,1
      b]thiophene indicate the existence of polar sulfur-containing metabolites that
      have escaped detection and identification.

PMID- 9783423
TI  - Alterococcus agarolyticus, gen.nov., sp.nov., a halophilic thermophilic bacterium
      capable of agar degradation.
AB  - Five strains of facultatively anaerobic moderately thermophilic bacteria were
      isolated from two hot springs in the intertidal zone of Lutao, Taiwan. They
      produced extracellular agarase on agar medium, yielding reducing sugars and
      organic acids as the end products under either aerobic or anaerobic conditions.
      The growth temperature range was approximately 38-58 degrees C with an optimal
      temperature of about 48 degrees C. The five strains tolerated a relatively narrow
      pH range from 7.0 to 8.5. They were Gram-negative halophiles growing optimally at
      2.0-2.5% NaCl (ca. 0.34-0.43 M). They were capable of anaerobic growth by
      fermenting glucose and producing various organic acids such as butyrate,
      propionate, formate, lactate, and acetate. Cells grown in liquid medium were
      motile monotrichous cocci, normally 0.8-0.9 micron in diameter. They possessed
      saturated anteiso-15-carbon acid (anteiso-C15:0) as the most abundant cellular
      fatty acid (46.0-51.3 mo1%) and had G + C contents ranging from 65.5 to 67.0
      mo1%. They are the first thermophiles found to degrade agar and also the first
      halophilic thermophilic bacteria known to be capable of both aerobic and
      anaerobic fermentative growth. These bacteria are considered to represent a new
      genus that we named Alterococcus, and Alterococcus agarolyticus is the type
      species.

PMID- 9783424
TI  - Purification, characterization, and antifungal activity of chitinase from
      Fusarium chlamydosporum, a mycoparasite to groundnut rust, Puccinia arachidis.
AB  - Chitinase (EC 3.2.1.14) was isolated from the culture filtrate of Fusarium
      chlamydosporum and purified by ion-exchange chromatography and gel filtration.
      The molecular mass of purified chitinase was 40 kDa as estimated by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis. Chitinase was optimally
      active at a pH of 5 and stable from pH 4 to 6 and up to 40 degrees C. Among the
      metals and inhibitors tested, mercuric chloride completely inhibited the enzyme
      activity. The activity of chitinase was high on colloidal and pure chitin. The
      purified chitinase inhibited the germination of uredospores of Puccinia arachidis
      and also lysed the walls of uredospores and germ tubes. The results from these
      experiments indicated that chitinase of F. chlamydosporum plays an important role
      in the biocontrol of groundnut rust.

PMID- 9783425
TI  - Investigation of serine hydroxymethyltransferase in methanogens.
AB  - The cofactor specificity of serine hydroxymethyltransferase (SHMT) activities was
      tested in extracts of several methanogens using tetrahydromethanopterin (H4MPt)
      from Methanobacterium thermoautotrophicum Marburg, tetrahydrosarcinapterin
      (H4SPt) from Methanosarcina barkeri, and tetrahydrofolate (H4folate) as the
      potential C1 carrier. In Methanosphaera stadtmanae and Methanococcus
      thermolithotrophicus, the activities were H4MPt dependent. In Methanospirillum
      hungatei GP1, Methanosaeta concilii, Methanolobus tindarius, and Methanosarcina
      barkeri Fusaro, the activities were strictly H4folate dependent. H4SPt was
      reactive with the SHMT of Methanosphaera stadtmanae but not with that of
      Methanosarcina barkeri. In both Methanosarcina barkeri and Methanospirillum
      hungatei, pyridoxal phosphate stimulated SHMT activity. The apparent K(m) values
      for H4folate and L-serine were 0.086 and 0.29 mM in Methanosarcina barkeri and
      0.065 and 0.31 mM in Methanospirillum hungatei, respectively.

PMID- 9783426
TI  - Characterization of a gene locus from Erwinia amylovora with regulatory functions
      in exopolysaccharide synthesis of Erwinia spp.
AB  - In a genomic library of Erwinia amylovora, a locus has been identified that can
      suppress an Erwinia stewartii rcsA mutant. In addition, the locus induced a
      mucoid sticky phenotype of colonies in a wild-type strain of Erwinia stewartii
      and increased exopolysaccharide synthesis in several species of bacteria
      belonging to the genus Erwinia. An open reading frame was identified at this
      locus encoding a 225 amino acid protein that contained a helix-turn-helix motif
      typical of transcriptional regulators. The corresponding gene was subsequently
      named rcsV (regulator of capsular synthesis affecting viscosity). A mutant of
      rcsV in wild-type Erwinia amylovora had no detectable phenotype and produced
      typical levels of amylovoran under laboratory conditions. The rcsV gene on a high
      copy number plasmid under the control of its own promoter did not alter
      amylovoran production, in contrast to in-frame fusions of the structural gene in
      expression vectors. Since even the lac promoter was inert in the expression of
      rcsV, a DNA-binding protein could inhibit transcription of the gene in Erwinia
      amylovora. On the other hand, an Erwinia amylovora rcsA mutant was suppressed by
      rcsV when its promoter was replaced and the structural gene fused in-frame with
      lacZ' or malE. Northern blots, with total RNA from Erwinia amylovora, or promoter
      analysis using the GUS reporter gene did not show expression of rcsV in Erwinia
      amylovora, although primer extension analysis did. RcsV could be a component
      involved in the regulation of amylovoran synthesis, and gene expression may
      require an unknown external signal during the life cycle or pathogenesis of
      Erwinia amylovora.

PMID- 9783427
TI  - Gene sequences of the pcpB gene of pentachlorophenol-degrading Sphingomonas
      chlorophenolica found in nondegrading bacteria.
AB  - Bacteria isolated from a pentachlorophenol (PCP) contaminated site grew in the
      presence of 50 micrograms PCP/mL but were not able to degrade it in either liquid
      medium or the presence of 1% sterile potting soil as a solid support. Probes
      developed using the gene sequence of PCP-4-monooxygenase (pcpB) from Sphingomonas
      chlorophenolica sp.nov hybridized to two separate isolates. Identification based
      on fatty acid methyl ester profiles (Sherlock), substrate utilization (BIOLOG),
      and 16S rRNA showed that the two strains were different from each other and from
      Sphingomonas chlorophenolica. Sequences from these isolates, amplified by
      polymerase chain reaction, confirmed the homology with pcpB. The presence of pcpB
      sequences in these nondegraders indicated that growth and hybridization data
      alone were insufficient for predicting degradation capability.

PMID- 9783428
TI  - Cloning of the Nocardia corallina polyhydroxyalkanoate synthase gene and
      production of poly-(3-hydroxybutyrate-co-3-hydroxyhexanoate) and poly-(3
      hydroxyvalerate-co-3-hydroxyheptanoate).
AB  - The polyhydroxyalkanoate (PHA) synthase gene (phaCNc) from Nocardia corallina was
      identified in a lambda library on a 6-kb BamHI fragment. A 2.8-kb XhoII
      subfragment was found to contain the intact PHA synthase. This 2.8-kb fragment
      was subjected to DNA sequencing and was found to contain the coding region for
      the PHA synthase and a small downstream open reading frame of unknown function.
      On the basis of DNA sequence, phaCNc is closest in homology to the PHA synthases
      (phaCPaI and phaCPaII) of Pseudomonas aeruginosa (approximately 41% identity and
      55% similarity). The 2.8-kb XhoII fragment containing phaCNc was subcloned into
      broad host range mobilizable plasmids and transferred into Escherichia coli,
      Klebsiella aerogenes (both containing a plasmid bearing phaA and phaB from
      Ralstonia eutropha), and PHA-negative strains of R. eutropha and Pseudomonas
      putida. The recombinant strains were grown on various carbon sources and the
      resulting polymers were analyzed. In these strains, the PHA synthase from N.
      corallina was able to mediate the production of poly(3-hydroxybutyrate-co-3
      hydroxyhexanoate) containing high levels of 3-hydroxyhexanoate when grown on
      hexanoate and larger even-chain fatty acids and poly(3-hydroxyvalerate-co-3
      hydroxyheptanoate) containing high levels of 3-hydroxyheptanoate when grown on
      heptanoate or larger odd-chain fatty acids.

PMID- 9783429
TI  - Genetic analysis of microcin H47 immunity.
AB  - Microcin H47 is a bactericidal antibiotic produced by a natural Escherichia coli
      isolate. The genetic system encoding microcin production and immunity consists of
      at least seven clustered genes. Four of these are devoted to microcin
      biosynthesis and two genes are required for its secretion into the extracellular
      medium. The product of the seventh gene, mchI, determines the cell's self
      immunity. This gene was shown to encode a highly hydrophobic 69-residue peptide.
      Analysis of the MchI amino acid sequence, as well as the characterization of MchI
      PhoA hybrid proteins, indicated that the microcin immunity product is probably
      exported out of the cytoplasm and remains an integral membrane peptide. This
      localization of the immunity peptide points to the cellular membrane as the site
      of action of microcin H47.

PMID- 9783431
TI  - Pressure and temperature dependence of enantioselective excited-state quenching
      of chiral Tb(III) and Eu(III) tris(pyridine-2,6-dicarboxylate) chelates by
      various C-type ferricytochromes.
AB  - For mitochondrial ferricytochrome c from horse, cow and tuna and for bacterial
      cytochrome c-550 from Paracoccus versutus, the pressure and temperature
      dependence of their quenching of racemic Tb(DPA)3(3-) and Eu(DPA)3(3-) (DPA =
      pyridine-2,6-dicarboxylate) luminescence in aqueous solution is investigated. Of
      these energy transfer reactions the activation volumes (delta V#) and energies
      (Ea) are determined for the ranges P = 0-3 kbar and T = 15-40 degrees C. For the
      lambda enantiomers of Tb(DPA)3(3-) and Eu(DPA)3(3-), delta V# and Ea are almost
      the same for all proteins: 0.4 < or = delta V# < or = 1.1 cm3/mol and 0 < or = Ea
      < or = 2 kJ/mol. For the delta enantiomer, whose luminescence is quenched faster,
      the activation parameters vary significantly with the origin of the protein and
      they are different for Tb(DPA)3(3-) and Eu(DPA)3(3-). Values for delta V#, delta
      range from +4.9 +/- 0.5 (Eu/horse) to +0.5 +/- 0.5 cm3/mol (Tb/tuna); Ea ranges
      from +8 +/- 1 (Tb/cow) to -1 +/- 1 kj/mol (Tb/tuna). The degree of
      enantioselectivity in the quenching (Eq) by cytc from horse, cow, chicken and
      pigeon is almost the same and markedly higher than from tuna. The differing
      quenching characteristics of the tuna protein are ascribed to the amino acid
      variations near the exposed heme edge: Ile9-->Thr, Thr28-->Val and/or Phe46-
      >Tyr. Other variations in this region, Thr47-->Ser and Ala15-->Ser, do not affect
      Eq.

PMID- 9783430
TI  - Biomolecules interactions and competitions by non-immobilised ligand interaction
      assay by circular dichroism.
AB  - Non-immobilised ligand interaction assay (NILIA) by CD spectroscopy provides an
      excellent technique to study molecular interactions in solution. Here are
      discussed molecular interactions of several systems that involve hosts and
      ligands with wide range of molecular sizes. Cytokine rhGM-CSF (14.6 kDa) bound to
      alpha-chain hGM-CSF receptor fragment (2 kDa, Kd = 35 microM), proline rich
      peptide (1.5 kDa) bound to fynSH3 domain (8 kDa, Kd = 28 microM), tumour imaging
      peptide (2 kDa) bound to mucin antigenic fragment (2 kDa, Kd = 20 microM),
      monoclonal antibody (150 kDa) bound to antigenic protein (120 kDa, Kd = 50 nM).
      Reconstitution of Cytochrome b5 (Cyt b5) from apo-Cyt b5 and hemin (Kd = 1.6 nM),
      correct protein folding of reconstituted porphobilinogen deaminase from apo
      cofactorless form achieved using the product of the enzyme catalysis,
      preuroporphyrinogen, rather than porphobilinogen substrate. Competition studies
      of bound non-chiral drugs diclofenac and diazepam to carrier proteins such as HSA
      in the presence of fatty acids are few of the examples of the studies carried out
      by NILIA-CD spectroscopy. The CD changes in either backbone, aromatic side-chains
      and disulphide regions were used accordingly to screen qualitatively and
      quantitatively ligand binding in vitro. CD data were fitted by non-linear
      regression to the general equilibrium reaction of a single-binding site. NILIA-CD
      is fast compared to NMR, gives information on conformational changes due to
      interaction, avoids masking of the binding site due to immobilisation and
      requires no radiolabelling. NILIA-CD is thus an ideal technique for interaction,
      activity, screening studies.

PMID- 9783432
TI  - Enantioselective biotransformation of aryl-isopropyl, -isopropenyl, and -propenyl
      groups by the rabbit or by the rat.
AB  - Thirteen kinds of aromatic compounds (Alkyl- and alkenyl-) were administered to
      rabbits and the chiralities of their optical active metabolite were determined by
      the synthesis of the enantiomers or their derivatives. This work has revealed
      many examples of enantioselective biotransformations and chiral inversion in the
      rabbits and mechanisms for this inversion have been proposed. The
      enantioselective hydration of transanethole epoxide was also examined in vitro in
      rat liver microsomes and possible mechanisms of this process are also discussed.

PMID- 9783433
TI  - Vlado Prelog (1906-1998): Nobel Laureate and stereochemist par excellence.

PMID- 9783434
TI  - Strength of synaptic transmission at neuromuscular junctions of crustaceans and
      insects in relation to calcium entry.
AB  - Crustacean and insect neuromuscular junctions typically include numerous small
      synapses, each of which usually contains one or more active zones, which possess
      voltage-sensitive calcium channels and are specialized for release of synaptic
      vesicles. Strength of transmission (the number of quantal units released per
      synapse by a nerve impulse) varies greatly among different endings of individual
      neurons, and from one neuron to another. Ultrastructural features of synapses
      account for some of the physiological differences at endings of individual
      neurons. The nerve terminals that release more neurotransmitter per impulse have
      a higher incidence of synapses with more than one active zone, and this is
      correlated with more calcium build-up during stimulation. However, comparison of
      synaptic structure in neurons with different physiological phenotypes indicates
      no major differences in structure that could account for their different levels
      of neurotransmitter release per impulse, and release per synapse differs among
      neurons despite similar calcium build-up in their terminals during stimulation.
      The evidence indicates differences in calcium sensitivity of the release process
      among neurons as an aspect of physiological specialization.

PMID- 9783435
TI  - Neuromuscular glutamatergic and GABAergic channels.
AB  - Our laboratory has worked extensively on glutamatergic and GABA-ergic channels,
      predominantly in crayfish, but also in locust, Drosophila and recently Ascaris.
      Channel currents were recorded in the different modes of the patch-clamp
      technique (Hamill et al., 1981). The opening kinetics of the channels were
      derived from open and closed time histograms obtained from single channel
      recordings. From these, channel conductances could also be evaluated. The most
      relevant data were obtained by very rapidly rising and falling pulses (time of
      change about 0.1 ms) of agonists applied to outside-out patches containing the
      respective channels (Franke et al., 1987). From such recordings we constructed
      dose-response curves for peak and steady-state currents, for the rise times of
      the currents and for the time constants of desensitization. In double-pulse
      experiments we measured recovery from desensitization and predesensitization due
      to low agonist concentrations. For most of the channel types, we succeeded in
      constructing a reaction scheme which in computer simulations mimicked channel
      behaviour to a good approximation.

PMID- 9783436
TI  - Drosophila melanogaster as a model system for the study of the function of
      calcium/calmodulin-dependent protein kinase II in synaptic plasticity.
AB  - Drosophila melanogaster has been used as a biological model system for almost a
      century. In the last several decades, Drosophila has been used as a system to
      probe the molecular basis of behavior and discoveries in the fly have been at the
      forefront of the elucidation of important basic mechanisms. This review will
      outline the variety of approaches that make Drosophila an excellent model system
      with which to study the function of the enzyme calcium/calmodulin-dependent
      protein kinase II (CaMKII) in synaptic plasticity. CaMKII has a well documented
      role in behavior and synaptic plasticity in both vertebrates and invertebrates.
      The behavioral and genetic richness of Drosophila allow for a multi-level
      approach to understanding the physiological roles of this enzyme's function.

PMID- 9783437
TI  - A new approach to insect-pest control--combination of neurotoxins interacting
      with voltage sensitive sodium channels to increase selectivity and specificity.
AB  - Voltage-sensitive sodium channels are responsible for the generation of
      electrical signals in most excitable tissues and serve as specific targets for
      many neurotoxins. At least seven distinct classes of neurotoxins have been
      designated on the basis of physiological activity and competitive binding
      studies. Although the characterization of the neurotoxin receptor sites was
      predominantly performed using vertebrate excitable preparations, insect neuronal
      membranes were shown to possess similar receptor sites. We have demonstrated that
      the two mutually competing anti-insect excitatory and depressant scorpion toxins,
      previously suggested to occupy the same receptor site, bind to two distinct
      receptors on insect sodium channels. The latter provides a new approach to their
      combined use in insect control strategy. Although the sodium channel receptor
      sites are topologically separated, there are strong allosteric interactions among
      them. We have shown that the lipid-soluble sodium channel activators, veratridine
      and brevetoxin, reveal divergent allosteric modulation on scorpion alpha-toxins
      binding at homologous receptor sites on mammalian and insect sodium channels. The
      differences suggest a functionally important structural distinction between these
      channel subtypes. The differential allosteric modulation may provide a new
      approach to increase selective activity of pesticides on target organisms by
      simultaneous application of allosterically interacting drugs, designed on the
      basis of the selective toxins. Thus, a comparative study of neurotoxin receptor
      sites on mammalian and invertebrate sodium channels may elucidate the structural
      features involved in the binding and activity of the various neurotoxins, and may
      offer new targets and approaches to the development of highly selective
      pesticides.

PMID- 9783438
TI  - Odorant response of individual sensilla on the Drosophila antenna.
AB  - We have documented odor responses of all morphological classes of sensilla on the
      surface of the Drosophila antenna: sensilla basiconica, sensilla trichodea, and
      sensilla coeloconica. Both subtypes of s. basiconica, large and small, respond to
      odors. S. trichodea fall into different functional types. Type 1 appears narrowly
      tuned, as it responded only to cis-vaccenyl acetate, believed to be a pheromone.
      Type 2 responded to trans-2-hexenal and 4-methyl cyclohexanol. These two types of
      s. trichodea are differentially distributed on the antennal surface, and have
      dramatically different frequencies of spontaneous action potentials. Likewise,
      there are multiple types of s. coeloconica. One type if broadly tuned, responding
      most strongly to a test stimulus of butyric acid, but also to a variety of other
      odors; it is restricted to the dorso-medial portion of the third antennal
      segment. A second type gave detectable responses only to trans-2-hexenal. These
      results demonstrate that all classes of sensilla are olfactory, and they reveal
      the organizational complexity of the Drosophila olfactory system.

PMID- 9783439
TI  - Elements of the olfactory signaling pathways in insect antennae.
AB  - Owing to their enormous ability to recognize airborne molecules, insects have
      long been used as model systems for studying various aspects of olfaction. Modern
      biological techniques have opened new avenues for exploring the molecular
      mechanisms underlying the complex signaling processes in chemosensory neurons.
      Biochemical and molecular analyses have allowed the identification of molecular
      elements of the olfactory reaction pathways and have shed light on mechanisms
      that account for the sensitivity and specificity of the chemosensory system.

PMID- 9783440
TI  - Insect circadian rhythms and photoperiodism.
AB  - Two clock-controlled processes, overt circadian rhythmicity and the photoperiodic
      induction of diapause, are described in the blow fly, Calliphora vicina and the
      fruit fly, Drosophila melanogaster. Circadian locomotor rhythms of the adult
      flies reflect endogenous, self-sustained oscillations with a temperature
      compensated period. The free-running rhythms become synchronised (entrained) to
      daily light:dark cycles, but become arrhythmic in constant light above a certain
      intensity. Some flies show fragmented rhythms (internal desynchronisation)
      suggesting that overt rhythmicity is the product of a multioscillator
      (multicellular) system. Photoperiodic induction of larval diapause in C. vicina
      and of ovarian diapause in D. melanogaster is also based on the circadian system
      but seems to involve a separate mechanism at both the molecular and neuronal
      levels. For both processes in both species, the compound eyes and ocelli are
      neither essential nor necessary for photic entrainment, and the circadian clock
      mechanism is not within the optic lobes. The central brain is the most likely
      site for both rhythm generation and extra-optic photoreception. In D.
      melanogaster, a group of lateral brain neurons has been identified as important
      circadian pacemaker cells, which are possibly also photo-sensitive. Similar
      lateral brain neurons, staining for arrestin, a protein in the phototransduction
      'cascade' and a selective marker for photoreceptors in both vertebrates and
      invertebrates, have been identified in C. vicina. Much less is known about the
      cellular substrate of the photoperiodic mechanism, but this may involve the pars
      intercerebralis region of the mid-brain.

PMID- 9783442
TI  - Behavioral analysis of Drosophila mutants displaying abnormal male courtship.
AB  - We describe six recessive autosomal male sterile mutations in Drosophila,
      generated by mobilization of single P-elements, exhibiting abnormal male
      courtship behavior. Detailed analysis of courtship behavior elicited by virgin
      wild type females indicated that five of the six mutants are affected in the
      early steps of courtship. The sixth mutant is blocked at the step of attempted
      copulation which occurs later in the courtship sequence. All of the mutants have
      normal olfactory responses and normal locomotor activity. No defect in the visual
      modality has been observed for the five mutants affected in the initiation of
      courtship. The mutant blocked at attempted copulation lacks the 'on' and 'off'
      transients, but this appears to be due to genetic background rather than the
      mutation itself. Abnormal spermatogenesis was observed in five of the mutants.
      Spermatogenic defects vary and include lesions in the proliferation of the
      germline, in meiosis, and in the differentiation and maturation of the spermatids
      into motile sperm.

PMID- 9783441
TI  - Genetic analysis of axon pattern formation in the embryonic CNS of Drosophila.
AB  - The major axon tracts in the embryonic CNS of Drosophila are organised in a
      simple, ladder-like pattern. Each neuromere contains two commissures which
      connect the contra-lateral sides and two longitudinal connectives which connect
      the different neuromeres along the anterior-posterior axis. The commissures form
      in close association with only few cells located at the CNS midline. The
      formation of longitudinal connectives depends in part on the presence of specific
      lateral glial cells. To unravel the genes underlying the formation of the
      embryonic CNS axon pattern, we conducted a saturating F2 EMS mutagenesis,
      screening for mutations, which disrupt this process. The analyses of the
      identified mutations lead to a simple sequential model on axon pattern formation
      in embryonic CNS.

PMID- 9783444
TI  - Degradation of a radiolabeled juvenile hormone analog using two insect species.
AB  - A synthetic insect juvenile hormone analog (a juvenoid), ethyl N-[2-[4-[[2,2
      (ethylenedioxy)cyclohexyl]methyl]phenox]ethyl]carbam ate, which has displayed
      high biological activity against different insect species and high stability
      under field conditions, was selected as a biologically active model compound for
      a study of a juvenile hormone analog degradation. The biologically active
      compound itself and its three diversely radiolabeled derivatives were applied to
      the flesh fly (Sarcophaga bullata) or the tsetse fly (Glossina palpalis),
      respectively. Monitoring of a fate of the applied juvenile hormone analog was
      carried out using a detection method of the radioactivity microdistribution
      within the whole insect body in combination with a radio high performance liquid
      chromatography (radio-HPLC), both of whole-body extracts made in different, but
      in advance scheduled, time intervals, and of extracts of insect excreta
      accumulated over an eight-day experiment.

PMID- 9783443
TI  - A subtractive cDNA library from an identified regenerating neuron is enriched in
      sequences up-regulated during nerve regeneration.
AB  - We have constructed a subtractive cDNA library from regenerating Retzius cells of
      the leech, Hirudo medicinalis. It is highly enriched in sequences up-regulated
      during nerve regeneration. Sequence analysis of selected recombinants has
      identified both novel sequences and sequences homologous to molecules
      characterised in other species. Homologies include alpha-tubulin, a calmodulin
      like protein, CAAT/enhancer-binding protein (C/EBP), protein 4.1 and synapsin.
      These types of proteins are exactly those predicted to be associated with axonal
      growth and their identification confirms the quality of the library. Most
      interesting, however, is the isolation of 5 previously uncharacterised cDNAs
      which appear to be up-regulated during regeneration. Their analysis is likely to
      provide new information on the molecular mechanisms of neuronal regeneration.

PMID- 9783445
TI  - cDNA cloning of a mandibular organ inhibiting hormone from the spider crab
      Libinia emarginata.
AB  - Mandibular organs (MO) produce a crustacean juvenile hormone, methyl farnesoate
      (MF). MO activity is negatively regulated by factors, called mandibular organ
      inhibiting hormones (MOIHs), from the crustacean sinus gland X-organ complex in
      the eyestalks. Three MOIHs have been isolated previously from the spider crab
      Libinia emarginata and are characterized as members of the crustacean
      hyperglycemic hormone (CHH) neuropeptide family. In the research reported here, a
      full length cDNA sequence of 972 bp of a MOIH was isolated by screening a cDNA
      library constructed from the eyestalks of Libinia emarginata. This cDNA sequence
      encodes a preprohormone peptide with 137 amino acid residues, including a 26
      amino acid long signal peptide, a 34-amino acid long precursor peptide, a dibasic
      peptide, the full length of 72-amino acid long MOIH, and a tri-peptide Gly-Lys
      Lys which designates the potential amidation site at the C-terminus of the mature
      peptide.

PMID- 9783447
TI  - Alzheimer's drug design based upon an invertebrate toxin (anabaseine) which is a
      potent nicotinic receptor agonist.
AB  - Naturally occurring toxins can often serve as useful chemical tools for
      investigating signalling processes in nervous and other systems. Tetrodotoxin and
      alpha-bungarotoxin are prime examples of toxins which are widely used in
      neurobiological research. Some toxins may also become molecular models for
      designing new drugs. Usually drugs are small, non-peptide molecules, as these
      display better bioavailability, longer durations of action and are less likely to
      generate immune responses. The relatively large size and conformational
      flexibility of peptides and protein toxins makes them more challenging molecular
      models for rational drug design. This article considers a marine invertebrate
      toxin, anabaseine, and describes how manipulation of the structure of this
      alkaloid has provided a drug candidate which selectively stimulates mammalian
      brain alpha7 nicotinic receptors. Numerous anabaseine analogs were synthesized
      and subjected to a variety of pharmacological, behavioral and toxcicological
      tests. This led to the choice of GTS-21 (also known as 3-(2,4
      dimethoxybenzylidene)-anabaseine or DMXBA), as a drug candidate for the treatment
      of Alzheimer's dementia. The chemical and pharmacological properties of GTS-21
      are compared with those of the initial lead compound, anabaseine.

PMID- 9783446
TI  - Control of ecdysteroidogenesis: activation and inhibition of prothoracic gland
      activity.
AB  - The ecdysteroid hormones, mainly 20-hydroxyecdysone (20E), play a pivotal role in
      insect development by controlling gene expression involved in molting and
      metamorphosis. In the model insect Manduca sexta the production of ecdysteroids
      by the prothoracic gland is acutely controlled by a brain neurohormone,
      prothoracicotropic hormone (PTTH). PTTH initiates a cascade of events that
      progresses from the influx of Ca2+ and cAMP generation through phosphorylation of
      the ribosomal protein S6 and S6-dependent protein synthesis, and concludes with
      an increase in the synthesis and export of ecdysteroids from the gland. Recent
      studies indicate that S6 phosphorylation probably controls the steroidogenic
      effect of PTTH by gating the translation of selected mRNAs whose protein products
      are required for increased ecdysteroid synthesis. Inhibition of S6
      phosphorylation prevents an increase in PTTH-stimulated protein synthesis and
      subsequent ecdysteroid synthesis. Two of the proteins whose translations are
      specifically stimulated by PTTH have been identified, one being a beta tubulin
      and the other a heat shock protein 70 family member. Current data suggest that
      these two proteins could be involved in supporting microtubule-dependent protein
      synthesis and ecdysone receptor assembly and/or function. Recent data also
      indicate that the 20E produced by the prothoracic gland feeds back upon the gland
      by increasing expression and phosphorylation of a specific USP isoform that is a
      constituent of the functional ecdysone receptor. Changes in the concentration and
      composition of the ecdysone receptor complex of the prothoracic gland could
      modulate the gland's potential for ecdysteroid synthesis (e.g. feedback
      inhibition) by controlling the levels of enzymes or other proteins in the
      ecdysteroid biosynthetic pathway.

PMID- 9783449
TI  - Molecular cloning and characterization of a superoxide dismutase (sod) gene in
      Pneumocystis carinii.
AB  - This work reports the isolation and characterization of a gene encoding a
      superoxide dismutase (SOD, EC.1.15.1.1.) from Pneumocystis carinii derived from
      rat. Sense and antisense oligonucleotides, deduced from SOD amino acid sequences
      from a wide variety of organisms, allowed amplification of a 669 bp genomic DNA
      fragment specific to this P. carinii. RACE-PCR was used to obtain the major part
      of the complementary DNA; the 5'- and 3'-genomic regions were obtained
      respectively from a Mbol subgenomic library and from an amplified fragment using
      oligonucleotides designed from the cDNA sequence. Comparison of genomic and cDNA
      sequences showed an open reading frame of 660 bp interrupted by seven small
      introns. The deduced amino acid sequence contained 220 residues. Protein sequence
      alignment demonstrated the highest homology (50.5% identity; 70.3% similarity)
      with Saccharomyces cerevisiae manganese-SOD (MnSOD) suggesting that P. carinii
      SOD belongs to the mitochondrial MnSOD group. A putative targeting peptide found
      at the 5'-end of the P. carinii SOD sequence also suggested its mitochondrial
      localization.

PMID- 9783448
TI  - Polycyclic dinitriles: a novel class of potent GABAergic insecticides provides a
      new radioligand, [3H]BIDN.
AB  - The polycyclic dinitriles are a potent class of insecticides which are non
      competitive GABA (gamma-aminobutyric acid) antagonists acting at the convulsant
      site. Comparison with other classes of GABA convulsant site ligands using
      molecular modelling has shown significant structural similarities. We have
      developed a pharmacophore model which unifies this class and some previous
      classes of GABA convulsants. Key pharmacophore elements are a polarizable
      functionality separated by a fixed distance from two H-bond accepting elements.
      This model is based on information from X-ray crystal structures and Sybyl using
      the Tripos force field. Using this pharmacophore model, numerous structural
      modifications were explored to enhance understanding of structure-activity
      relationships at the GABA receptor convulsant site of insects and mammals. A
      radiolabelled bicyclic dinitrile, [3H]BIDN [3H]3,3-bis-trifluoromethyl
      bicyclo[2,2,1]heptane-2,2-dicarbonitrile+ ++), was prepared from this area of
      chemistry and was used as a probe for the interaction of polycyclic dinitriles at
      the target site.

PMID- 9783450
TI  - Insights on the diversity within a "species" of Thalassicolla (Spumellarida)
      based on 16S-like ribosomal RNA gene sequencing.
AB  - We compared 16S-like ribosomal RNA (rRNA) coding regions of samples of the
      solitary spumellarian radiolarian Thalassicolla nucleata collected from the
      Sargasso Sea and the Pacific Ocean. Sequences derived from these locations showed
      variability in both length and base-pair composition. This level of sequence
      variability is similar to the degree of variability reported in the literature
      for species- or even genus-level distinctions. Explanations for our results
      include multiple alleles for the rRNA gene, or the existence of multiple species
      of Thalassicolla that are morphologically indistinguishable. The seven existing
      descriptions of Thalassicolla species, including T. nucleata, are discussed in
      view of these molecular findings and with reference to our current understanding
      of the physiology and life cycle of the spumellarian radiolaria.

PMID- 9783451
TI  - Paramecium tetraurelia encodes unconventional actin containing short introns.
AB  - The polymerase chain reaction was used to amplify and clone an actin gene
      fragment from Paramecium tetraurelia. This DNA fragment was 1,138 bp long, more
      than 96% of the actin coding sequence, and contained four in-frame UAA codons and
      two small introns located at positions unique in the actin intron catalogue. This
      is the first report for the phylum Ciliophora of an actin gene containing
      introns. The deduced amino acid sequence of this actin fragment shared 58-77%
      identity with other actins. When compared with rabbit alpha-muscle actin,
      similarities were observed mainly in subdomains 1 and 3, whereas subdomains 2 and
      4 appeared to be more divergent.

PMID- 9783452
TI  - Adhesion of Plasmodium gallinaceum ookinetes to the Aedes aegypti midgut: sites
      of parasite attachment and morphological changes in the ookinete.
AB  - Plasmodium gallinaceum ookinetes adhered to Aedes aegypti midgut epithelia when
      purified ookinetes and isolated midguts were combined in vitro. Ookinetes
      preferentially bound to the microvillated luminal surface of the midgut, and they
      seemed to interact with three types of structures on the midgut surface. First,
      they adhered to and migrated through a network-like matrix, which we have termed
      microvilli-associated network, that covers the surface of the microvilli. This
      network forms on the luminal midgut surface in response to blood or protein
      meals. Second, the ookinetes bound directly to the microvilli on the surface of
      the midgut and were occasionally found immersed in the thick microvillar layer.
      Third, the ookinetes associated with accumulations of vesicular structures found
      interspersed between the microvillated cells of the midgut. The origin of these
      vesicular structures is unknown, but they correlated with the surface of midgut
      cells invaded by ookinetes as observed by TEM. After binding to the midgut,
      ookinetes underwent extensive morphological changes: they frequently developed
      one or more annular constrictions, and their surface roughened considerably,
      suggesting that midgut components remain bound to the parasite surface. Our
      observations suggest that, in a natural infection, the ookinete interacts in a
      sequential manner with specific components of the midgut surface. Initial binding
      to the midgut surface may activate the ookinete and cause morphological changes
      in preparation for invasion of the midgut cells.

PMID- 9783454
TI  - Molecular characterization of a Plasmodium chabaudi erythrocyte membrane
      associated protein with glutamate-rich tandem repeats.
AB  - The malarial parasite dramatically affects the structure and function of the
      erythrocyte membrane by exporting proteins that specifically interact with the
      host membrane. This report describes the complete sequence and some biochemical
      properties of a 93-kDa Plasmodium chabaudi chabaudi protein that interacts with
      the host erythrocyte membrane. Approximately 40% of the deduced protein sequence
      consists of tandem repeats of 14 amino acids that are rich in glutamic acid
      residues. Comparison of the repeat sequences from two different P. c. chabaudi
      strains derived from the same initial isolate revealed an exact duplication of
      294 nucleotides suggesting a recent unequal crossing-over event. However, in
      spite of this potentially high level of intragenic recombination activity, the
      repeat sequences from P. c. adami are rather conserved suggesting structural or
      functional constraints on the protein and tandem repeats. The 93-kDa protein
      exists in an oligomeric form as revealed by gel filtration chromatography and non
      denaturing gel electrophoresis. A predominantly alpha-helical predicted secondary
      structure and a discrepancy between the estimated molecular sizes determined from
      non-denaturing gel electrophoresis and gel filtration chromatography suggest that
      the protein is a long rod-shaped or fibrillar, protein. Attributes shared between
      the 93-kDa protein, some P. falciparum proteins with glutamate-rich tandem
      repeats, and cytoskeletal proteins suggest that these parasite proteins function
      as cytoskeletal proteins that possibly stabilize the erythrocyte membrane.

PMID- 9783453
TI  - Structure of the large subunit rDNA from a diatom, and comparison between small
      and large subunit ribosomal RNA for studying stramenopile evolution.
AB  - The aim of this study was to compare the usefulness of complete small and large
      subunit rRNA, and a combination of both molecules, for reconstructing
      stramenopile evolution. To this end, phylogenies from species of which both
      sequences are known were constructed with the neighbor-joining, maximum
      parsimony, and maximum likelihood methods. Also the use of structural features of
      the rRNAs was evaluated. The large subunit rRNA from the diatom Skeletonema
      pseudocostatum was sequenced in order to have a more complete taxon sampling, and
      a group I intron was identified. Our results indicated that heterokont algae are
      monophyletic, with diatoms diverging first. However, as the analysis was
      restricted to a particular data set containing merely six taxa, the outcome has
      limited value for elucidating stramenopile relationships. On the other hand, this
      approach permits comparison of the performance of both rRNA molecules without
      interference from other factors, such as a different species selection for each
      molecule. For the taxa used, the large subunit rRNA clearly contained more
      phylogenetic information than the small subunit rRNA. Although this result can
      definitely not be generalized and depends on the phylogeny to be studied, in some
      cases determining complete large subunit rRNA sequences certainly seems
      worthwhile.

PMID- 9783455
TI  - Molecular phylogeny of microsporidians with particular reference to species that
      infect the muscles of fish.
AB  - Ribosomal DNA from eight species of microsporidians infecting fish have been
      sequenced. Seven of these species infect the skeletal muscle of fish
      (Pleistophora spp.) and one species infects migratory mesenchyma cells (Glugea
      anomala). These sequences, in addition to other available microsporidian rDNA
      sequences from a broad range of host taxa, have been used in phylogenetic
      analysis. This analysis revealed that muscle-infecting microsporidians from fish
      are a polyphyletic group, indicating that characters supposed to be important in
      the classification of the genus Pleistophora have to be re-evaluated. One
      character that probably has a polyphyletic origin is the amorphous coat, which
      has been extensively used in the definition of this genus. Furthermore, our
      results showed that the insect parasitizing Pleistophora spp. are not related to
      the true pleistophorans parasitic in skeletal muscle of fish. Phylogenetic
      analysis of small subunit rDNA sequences revealed disagreements between the
      molecular phylogeny and classifications based upon ultrastructure. Many of the
      morphological characters claimed to be important in microsporidian
      classifications appeared to have arisen several times during evolution: for
      example, the diplokaryon and sporophorous vesicles.

PMID- 9783457
TI  - Attachment of Trypanosoma cruzi epimastigotes to hydrophobic substrates and use
      of this property to separate stages and promote metacyclogenesis.
AB  - In vivo, epimastigotes of Trypanosoma cruzi colonize a lipidic superficial layer
      of the rectal cuticle of the vector Triatoma infestans. In vitro, epimastigotes
      of four cultured strains and one strain from reduviids use a terminal area of the
      flagellum to attach to a variety of artificial hydrophobic substances, such as
      hydrocarbons and a range of synthetic plastics. Trypomastigotes did not attach to
      these substrates. Hydrophilic molecules, such as neutral or negatively charged
      polysaccharides, did not facilitate binding. Epimastigotes and trypomastigotes
      were artificially bound by electrostatic forces to positively charged chitosan or
      DEAE-Sephacel over their entire surface. Tween 20 and lipid-binding serum albumin
      effectively inhibited the hydrophobic attachment. Based on this hydrophobic
      interaction of epimastigotes, a new chromatography technique has been devised to
      gently separate trypomastigotes from epimastigotes using octacosane-coated beads.
      Furthermore, the in vitro transformation of epimastigotes to trypomastigotes was
      enhanced if epimastigotes were permitted to attach to hydrophobic, wax-coated
      culture vessels.

PMID- 9783456
TI  - Cultured rat and purified human Pneumocystis carinii stimulate intra- but not
      extracellular free radical production in human neutrophils.
AB  - The production of free radicals in human neutrophils was studied in both
      Pneumocystis carinii derived from cultures of L2 rat lung epithelial-like cells
      and Pneumocystis carinii purified from human lung. Using the cytochrome C
      technique, which selectively measured extracellular superoxide generation, hardly
      any free radical production was observed after stimulation with cultured rat
      derived P. carinii. A chemiluminescence technique, which separately measured
      intra- and extracellular free radical production, was subsequently employed to
      differentiate the free radical generation. It was established that 1) P. carinii
      stimulated intra- but not extracellular free radical production in human
      neutrophils, 2) opsonized cultured rat-derived P. carinii stimulated human
      neutrophils to a strong intracellular response of superoxide production, and 3)
      opsonized P. carinii, purified from human lung also stimulated human neutrophils
      to produce intracellular free radicals.

PMID- 9783458
TI  - The small subunit ribosomal RNA gene sequence of Pleistophora anguillarum and the
      use of PCR primers for diagnostic detection of the parasite.
AB  - Using the polymerase chain reaction (PCR) and two primers for conserved regions
      of the small subunit ribosomal RNA (SSU-rRNA) of Microsporidia, a DNA segment
      about 1,195 base pairs long was amplified from a DNA template prepared from
      purified spores of the microsporidian species Pleistophora anguillarum. These
      spores had been isolated from adult eels (Anguilla japonica) with "Beko Disease."
      A comparison of sequence data from other microsporidian species showed P.
      anguillarum SSU-rRNA to be most similar to Vavraia oncoperae. When juvenile eels
      were artificially infected with P. anguillarum, enzyme-linked immunosorbent assay
      could detect a positive infection only 12 days post-infection. However, when
      suitable PCR primers were used, a DNA fragment of about 0.8 kb was detected from
      these juvenile eels after only 3 days post infection. No PCR product was obtained
      with templates prepared from clinically healthy control animals.

PMID- 9783459
TI  - The phylogenetic position of alpha- and beta-tubulins from the Chlorarachnion
      host and Cercomonas (Cercozoa).
AB  - Alpha and beta-tubulin genes from Chlorarachnion and an alpha-tubulin gene from
      Cercomonas have been characterised. We found the Cercomonas and Chlorarachnion
      alpha tubulins to be closely related to one another, confirming the proposed
      relationship of these genera. In addition, the Chlorarachnion host and Cercomonas
      also appear to be more distantly related to Heterolobosea, Euglenozoa,
      chlorophytes, heterokonts, and alveolates. Chlorarachnion was also found to have
      two distinctly different types of both alpha- and beta-tubulin, one type being
      highly-divergent. Chlorarachnion contains a secondary endosymbiont of green algal
      origin, raising the possibility that one type of Chlorarachnion tubulins comes
      from the host and the other from the endosymbiont. Probing pulsed field-separated
      chromosomes showed that the highly-divergent genes are encoded by the host
      genome, and neither alpha- nor beta-tubulin cDNAs were found to include 5'
      extensions that might serve as targeting peptides. It appears that Chlorarachnion
      has distinct and divergent tubulin paralogues that are all derived from the host
      lineage. One Chlorarachnion beta-tubulin was also found to be a pseudogene, which
      is still expressed but aberrantly processed. Numerous unspliced introns and
      deletions resulting from mis-splicing are contained in the mRNAs from this gene.

PMID- 9783460
TI  - In memoriam: Richard C. Starr (1924-1998).

PMID- 9783461
TI  - Heterotypic recognition of recombinant FMDV proteins by bovine T-cells: the
      polymerase (P3Dpol) as an immunodominant T-cell immunogen.
AB  - In this study we have examined the recognition of VP0, VP1, VP2, VP3 and P3Dpol
      by PBMC and CD4+ T-cells from infected, vaccinated-challenged, and multiply
      vaccinated (O1, A24, C1 or ASIA1) cattle using recombinant proteins of an O1
      serotype virus. The structural protein VP1 was recognised in an homotypic context
      whereas VP2, VP3, VP4 and P3Dpol were also recognised by T-cells from animals
      exposed to heterotypic viruses. Only the non-structural protein P3Dpol was
      consistently recognised by T-cells from the majority of animals examined and
      heterotypic recognition correlated with the presence of serologically detectable
      P3Dpol in purified virus. Thus, P3Dpol is a major cross-reactive
      immunodeterminant of FMDV, eliciting heterotypic T-cell responses and, therefore,
      with possible potential for inclusion in a subunit vaccine.

PMID- 9783462
TI  - DNA ligase gene disruptions can depress viral growth and replication in poxvirus
      infected cells.
AB  - Poxvirus-encoded DNA ligases are assumed to play a role in viral DNA replication;
      however mutational inactivation of vaccinia ligase has not been reported to
      affect viral growth rates in culture. This communication re-examines this
      surprising aspect of poxviral biology using both Shope fibroma virus (SFV) and
      vaccinia virus. SFV and vaccinia ligase deficiencies create essentially identical
      phenotypes. In particular, ligase-deficient SFV strains are mildly UV sensitive
      and etoposide resistant, phenotypes previously shown to characterize ligase
      deficient vaccinia strains. Moreover, we find that ligase mutations can inhibit
      the growth of both SFV and vaccinia virus in vitro. The poor growth observed in
      the absence of a viral ligase is correlated with a two- to tenfold reduction in
      viral and extragenomic DNA synthesis. This phenotype is host dependent. No
      differences in viral growth or DNA yield were seen when vaccinia strains were
      cultured on rabbit (SIRC) cells, but ligase deficiencies reduced growth and DNA
      yields when vaccinia was plated on BSC-40 cells or SFV on SIRC cells. Despite
      these replicative defects, mutational inactivation of SFV ligase produced no
      detectable increase in the number of viral DNA breaks and had no effect on virus
      catalyzed extragenomic DNA recombination or UV repair. We conclude that poxviral
      ligases do play a role in viral DNA replication, but the replicative defect is
      obscured in some cell lines.

PMID- 9783463
TI  - Nuclear import as a barrier to infection of human umbilical vein endothelial
      cells by human cytomegalovirus strain AD169.
AB  - Human embryonal fibroblasts (HEF) are fully permissive for infection by human
      cytomegalovirus (HCMV) strain AD169, whereas human umbilical vein endothelial
      cells (HUVEC) seem to form an almost complete barrier to infection with this
      virus. To investigate this difference in permissiveness, HCMV infection of both
      cell types was studied using in situ hybridisation (ISH) as well as
      immunocytochemistry to detect viral DNA and viral proteins. At 2 h post-infection
      (p.i.), viral DNA was detected dispersed throughout the cytoplasm in both HEF and
      HUVEC, indicating that HCMV enters all cells of both cell types. At 4 h p.i., the
      viral DNA was found in the nucleus in HEF, and at the same time expression of
      immediate early (IE) antigen was found. In contrast, in HUVEC the expression of
      the IE proteins occurred in a limited number of cells at 8 h p.i., while in most
      HUVEC an accumulation of viral DNA around the nuclei was observed at this time
      point. In HUVEC, the nuclear localisation of viral DNA was detected 16 h p.i. in
      a minority of cells, indicating that transport of HCMV DNA into the nucleus is
      considerably slower in HUVEC than in HEF. Furthermore, the number of HUVEC
      containing HCMV DNA decreased about six-fold between 8 and 48 h p.i., indicating
      that HCMV DNA is either transported into the nucleus or eliminated. Apparently,
      the lower permissiveness of HUVEC for the HCMV strain AD169 relative to HEF is
      due to inefficient transport of HCMV DNA into the nuclei of infected HUVEC.

PMID- 9783464
TI  - Human hepatocyte clonal cell lines that support persistent replication of
      hepatitis C virus.
AB  - We previously found that a human T-cell leukemia virus type I infected T-cell
      line, MT-2, was susceptible to hepatitis C virus (HCV) infection, and that cloned
      MT-2C cells could support HCV replication more persistently than the parental MT
      2 cells. Recently we found that a non-neoplastic hepatocyte line, PH5CH, showed
      good susceptibility to HCV infection. In this study, we cloned PH5CH cells to
      obtain cells that supported more persistent HCV replication, and consequently
      three clones (PH5CH1, PH5CH7 and PH5CH8) in which intracellular HCV RNA could be
      detected at least 25 days postinoculation (p.i.) were obtained. Semi-quantitative
      analysis of HCV RNA indicated that HCV replicated in these cloned PH5CH cells was
      released into the culture medium. Semi-quantitative analysis of internalized HCV
      RNA after treatment of cloned PH5CH cells and parental PH5CH cells with
      proteinase K immediately after virus inoculation revealed that PH5CH1, PH5CH7 and
      PH5CH8 cells contained 10-fold higher levels of HCV RNA than low susceptible
      cloned PH5CH or parental PH5CH cells. Furthermore, we demonstrated that HCV
      replication was maintained for 70-100 days in these three clonal lines when the
      temperature of cell culture after virus inoculation was reduced from 37 to 32
      degrees C. Moreover, we demonstrated that interferon alpha had antiviral effect
      on HCV-infected PH5CH8 cells. The three PH5CH clones obtained in this study will
      provide a useful tool for the study of HCV replication and proliferation, and for
      development of an assay system for antiviral agents.

PMID- 9783465
TI  - Changes in H3 influenza A virus receptor specificity during replication in
      humans.
AB  - Influenza A viruses of the H3 subtype caused the 1968 Hong Kong pandemic, the
      hemagglutinin (HA) gene being introduced into humans following a reassortment
      event with an avian virus. Receptor specificity and serum inhibitor sensitivity
      of the HA of influenza A viruses are linked to the host species. Human H3 viruses
      preferentially recognize N-acetyl sialic acid linked to galactose by alpha2,6
      linkages (Neu5Acalpha2,6Gal) and are sensitive to serum inhibitors, whereas avian
      and equine viruses preferentially recognize Neu5Acalpha2,3Gal linkages and are
      resistant to serum inhibitors. We have examined the receptor specificity and
      serum inhibitor sensitivity of H3 human influenza A viruses from the time they
      were introduced into the human population to gain insight into the mechanism of
      viral molecular evolution and host tropism. All of the viruses were sensitive to
      neutralization and hemagglutination inhibition by horse serum. Early H3 viruses
      were resistant to pig and rabbit serum inhibitors. Viruses isolated after 1977
      were uniformly sensitive to inhibition by pig and rabbit sera. The recognition of
      Neu5Acalpha2,3Gal or Neu5Acalpha2,6Gal linkages was not correlated with the serum
      sensitivity. These data showed that the receptor specificity of HA, measured as
      inhibitor sensitivity, has changed during replication in humans since its
      introduction from an avian virus.

PMID- 9783466
TI  - Comparison of amino acid sequences in hypervariable region-1 of hepatitis C virus
      clones between human inocula and the infected chimpanzee sera.
AB  - We analyzed nucleic and amino acid sequences of the hypervariable region (HVR)-1
      of the hepatitis C virus (HCV) from inocula and the infected chimpanzee sera. One
      milliliter each of 10(-5), 10(-3) and 10(-2) dilutions of serum no. 4, and those
      of 10(-4), 10(-5) and 10(-6) dilutions of serum no. 6 were inoculated to six
      different chimpanzees. Both inocula nos. 4 and 6 contained 10(7) copies of HCV
      RNA/ml. The two chimpanzees inoculated with 10(-4) and 10(-5) dilutions of no. 6
      were infective, while none of the dilutions from inoculum no. 4 were infective.
      Our results indicated that HCV RNA titer in sera did not correlate with in vivo
      infectivity. RNA from both inocula and the infected chimpanzee sera were
      extracted and transcribed to cDNA. The PCR products amplifying the HCV HVR-1 were
      incorporated into a vector, followed by transformation. Twenty colonies were
      picked up randomly from each sample. DNA was extracted and the DNA and amino acid
      sequences were determined. Genetic variations of 20 clones from inoculum no. 6
      were divided into six groups, whereas, 40 clones from infected chimpanzees were
      completely identical to the major quasispecies of inoculum no. 6 in amino acid
      sequences. The study suggested that the major quasispecies in the diluted inocula
      were transmitted and replicated.

PMID- 9783467
TI  - Establishment of a highly specific detection system for GB virus C (GBV-C) minus
      strand RNA.
AB  - Although the clinical relevance of GB virus C (GBV-C) is still elusive, this
      virus has been found with high prevalence in several groups of patients with
      liver disease. As was shown for hepatitis C virus (HCV), minus-strand RNA is
      supposed to function as a replicative intermediate. We have established a
      reliable and sensitive detection system for GBV-C minus-strand RNA based on
      nested RT-PCR (reverse transcription-polymerase chain reaction) with a tagged
      primer system. Sensitivity and specificity was extensively tested using in-vitro
      transcribed GBV-C sequences and genomic viral RNA. Specificity of the amplified
      fragments was proven by Southern blot hybridization. Using this detection system,
      we found the presence of GBV-C minus-strand RNA in 6/41 (14.6%) sera of GBV-C
      infected or GBV-C/HCV coinfected patients. No correlation with virological
      parameters such as amount of GBV-C plus-strand RNA, genotype or titer of HCV
      could be detected.

PMID- 9783468
TI  - Evidence for the internal location of actin in the pseudorabies virion.
AB  - Pseudorabies virions were purified by sucrose gradient and virion-associated
      proteins were examined. Cytoskeleton actin was found to be a component of virion
      preparation. In addition, abundant virion-associated actin was detected even
      after the virion preparation was treated with trypsin digestion or the viral
      envelope was removed by Triton X-100. This finding indicated that the location of
      actin is inside the pseudorabies virion. Furthermore, the possible involvement of
      actin in the life cycle of pseudorabies virus was studied by using cytochalasin
      D, an F-actin binding drug, and the result showed that cytochalasin D reduced the
      number of plaques and the size of the plaque of pseudorabies virus.

PMID- 9783469
TI  - Protein synthesis in pseudorabies virus-infected cells: decreased expression of
      protein kinase PKR, and effects of 2-aminopurine and adenine.
AB  - The impact of pseudorabies virus (PRV) infection on the synthesis of host cell
      proteins was studied. By metabolic labeling of protein synthesis with
      [35S]methionine, it was observed that the translation of cellular proteins was
      inhibited globally in the late phase of infection and viral proteins became the
      dominating products. Furthermore, immunoblot analysis showed that the total
      protein levels of two genes involved in translational regulation, namely the
      dsRNA-dependent protein kinase (PKR) and extracellular signal-regulated kinase 2
      (ERK2), decreased during late time of infection. Using [32P]orthophosphate
      labeling, it was observed that PRV infection also caused a decrease in the
      phosphorylation of intracellular PKR. Finally, using 2-aminopurine (2-AP, an
      inhibitor of serine/threonine protein kinase) or adenine (an isomer of 2-AP) to
      treat PRV-infected cells, we found that the inhibition of host protein synthesis
      by PRV was partially prevented by these two drugs, suggesting that 2-AP and
      adenine may share a same target and pathway to manifest the effect.

PMID- 9783470
TI  - Rabies virus replication induces Bax-related, caspase dependent apoptosis in
      mouse neuroblastoma cells.
AB  - Rabies virus has been shown to induce apoptosis in infected cells, but the
      intracellular pathway of cell killing is unknown. In this report, we show that
      rabies virus infected mouse neuroblastoma cells underwent chromatin condensation
      and DNA fragmentation within 48 h post-infection. An increased level of the
      apoptotic enhancer, Bax, was detected within 24 h after infection. In contrast to
      Bax, the production of the apoptotic antagonist, Bcl-2, remained unchanged.
      Shortly after detection of Bax, caspase 1 (ICE) was upregulated. Reduction of DNA
      fragmentation in rabies virus infected cultures pretreated with YVAD and DEVD
      suggested that more than one subfamily of caspase functioned in the death
      process. Significant degradation of the DNA repair enzyme, poly ADP-ribose
      polymerase (PARP), was revealed after caspase upregulation. This study showed
      that replication of rabies viruses in mouse neuroblastoma cells induced the Bax
      related death program leading to destruction of the DNA repair system probably by
      caspase activity.

PMID- 9783471
TI  - Complete sequence of echovirus 23 and its relationship to echovirus 22 and other
      human enteroviruses.
AB  - To define the relationship between echovirus 23 (E23) and other human
      enteroviruses, we have determined the complete nucleotide sequence of a strain of
      E23 isolated from a child with high fever in Connecticut in 1986 and compared the
      nucleotide and deduced amino acid sequences with those of other enteroviruses
      representing each of the major enterovirus phylogenetic groups, poliovirus type
      1, coxsackievirus A16, coxsackievirus B3, echovirus 22 (E22), and enterovirus 70.
      The genome of E23 (strain CT86-6760) was 7352 nucleotides in length, exclusive of
      the poly(A) tail, and the genome organization was typical of the picornaviruses.
      The nucleotide sequence and deduced amino acid sequences were most related to
      those of E22, a virus with which E23 shares many biological properties, and was
      quite divergent from the sequences of other enteroviruses (< 20% average amino
      sequence identity). These data lend further support to the suggestion that E22
      and E23 are distinct from members of the Enterovirus genus and that they should
      be reclassified in a separate genus within the Picornaviridae.

PMID- 9783472
TI  - Isolation and characterization of a gene expressed mainly in the gastric
      epithelium, a novel member of the ep37 family that belongs to the betagamma
      crystallin superfamily.
AB  - EP37 family proteins are non-lens members of the betagamma-crystallin
      superfamily, of which expression is observed in integumental tissues of the
      Japanese newt, Cynops pyrrhogaster. In the present study, a gene was isolated
      that has high homology with ep37 and is transcribed mainly in the gastric
      epithelial cells and hence designated gep. The predicted amino acid sequence of
      the gep cDNA contains four betagamma-crystallin motifs in the N-terminal half, as
      is the case in the integumental EP37 proteins. Immunohistochemical analysis
      showed that GEP protein was mainly localized on the luminal content of the
      surface mucous cells of the gastric epithelium in both premetamorphic larvae and
      adults. In addition, GEP protein was also expressed in fundic glands after
      metamorphosis. Considering the fact that beta- and gamma-crystallins are
      evolutionarily related to stress-induced proteins, this localization suggests
      that GEP protein may have an evolutionarily conserved role in protection against
      physico-chemical stresses, such as physical abrasion and autodigestion, during
      assimilation.

PMID- 9783473
TI  - Studies on fertilization in the teleost. I. Dynamic responses of fertilized
      medaka eggs.
AB  - In order to understand the mechanisms of fertilization in the teleost, the
      movements of the egg cortex, cytoplasmic inclusions and pronuclei were observed
      in detail in fertilized medaka Oryzias latipes eggs. The first cortical
      contraction occurred toward the animal pole region following the onset of
      exocytosis of cortical alveoli. The cortical contraction caused movement of oil
      droplets toward the animal pole where the germinal vesicle had broken down during
      oocyte maturation. The movement of oil droplets toward the animal pole region was
      frequently twisted in the right or left direction. The direction of the twisting
      movement has been correlated with the unilateral bending of non-attaching
      filaments on the chorion. The female pronucleus, which approached the male
      pronucleus from the vicinity of the second polar body, took a course to the
      right, left or straight along the s-p axis connecting the male pronucleus and the
      second polar body. The course of approach by the female pronucleus correlated
      with the bending direction of the non-attaching filaments that had been
      determined by rotation of the oocyte around the animal-vegetal axis during
      oogenesis. The first cleavage furrow also very frequently coincided with the
      axis. These observations suggest that dynamic responses of medaka eggs from
      fertilization to the first cleavage reflect the architecture dynamically
      constructed during oogenesis.

PMID- 9783474
TI  - Correlation between tectum formation and expression of two PAX family genes, PAX7
      and PAX6, in avian brains.
AB  - Heterotopic transplantation of brain vesicles between chick and quail were
      performed, and the correlation between tectum formation and the expression of two
      PAX family genes, PAX7 and PAX6, analyzed. Reciprocal transplantation between the
      prosencephalon and mesencephalon showed that formation of the tectum always
      coincided with induction/maintenance of PAX7 and suppression of PAX6, indicating
      that switch-on or -off of these two PAX family genes in region specific manners
      are responsible for the differentiation of brain vesicles into the tectum. On the
      other hand, transplantation of the mesencephalic floor plate into the dorsal
      mesencephalon suppressed PAX7 expression in the dorsal mesencephalon and changed
      its fate from the tectum to the tegmentum, indicating that factors in the
      mesencephalic floor plate suppress PAX7 and limit tectum territory to the dorsal
      part of the mesencephalon.

PMID- 9783476
TI  - Gravity influences the position of the dorsoventral axis in medaka fish embryos
      (Oryzias latipes).
AB  - To determine whether gravity influences the plane of bilateral symmetry in medaka
      embryos, zygotes were placed with their animal-vegetal axis orientated vertically
      and with their vegetal pole elevated. Then, at regular intervals during the first
      cell cycle, the zygotes were tilted 90 degrees for about 10 min and subsequently
      returned to their original orientation. In embryos tilted during the first half
      of the first cell cycle, the embryonic shield formed on the side that had been
      lowermost when the zygote was tilted. In embryos that were tilted twice, first in
      one direction and then in the opposite direction, the embryonic shield formed on
      the side that was lowermost the first time. When zygotes were centrifuged at 5 g,
      the embryonic shield formed on the outwardly radial (centrifugal) side of the
      embryo. The orientation of the array of parallel microtubules in the vegetal pole
      region was also influenced by tilting or centrifuging zygotes. No correlation was
      found between the positions of the polar body and the micropyle and the plane of
      bilateral symmetry. It was concluded that gravity influences both the plane of
      bilateral symmetry and the orientation of microtubules in the vegetal pole region
      of medaka embryos.

PMID- 9783475
TI  - Evidence for introduction of a variable G1 phase at the midblastula transition
      during early development in axolotl.
AB  - After fertilization in axolotl, the synchronous cell cleavages are triphasic (S,
      G2 and M phases). Midblastula transition (MBT) begins at the ninth cleavage and
      is the consequence of lengthening of cell cycles. By spectrofluorometry and
      incorporation of 3H thymidine into the nuclear DNA followed by autoradiography on
      individual cells, the time at which a G1 phase appears during early development
      was investigated. The present results show that the G1 phase was introduced for
      the first time at MBT and its duration was variable from one blastomere to
      another. This variability could account for lengthening of cell cycles and be
      required for zygotic transcriptions necessary for DNA replication. From this
      point of view, axolotl represents an interesting alternative amphibian model to
      identify regulators involved in the G1-S transition at MBT during early
      development.

PMID- 9783477
TI  - Tissue interaction regulates expression of a spasmolytic polypeptide gene in
      chicken stomach epithelium.
AB  - The primitive epithelium of embryonic chicken proventriculus (glandular stomach)
      differentiates, after day 6 of incubation, into luminal epithelium, which faces
      the lumen and abundantly secretes mucus, and glandular epithelium, which
      invaginates into mesenchyme and later expresses embryonic chicken pepsinogen
      (ECPg). So far it is not well understood how undifferentiated epithelial cells
      differentiate into these two distinct cell populations. Spasmolytic polypeptide
      (SP) is known to be expressed in surface mucous cells of mammalian stomach. In
      order to obtain the differentiation marker for proventricular luminal epithelial
      cells, we cloned a cDNA encoding chicken SP (cSP). Sequence analysis indicated
      that cSP has the duplicated cysteine-rich domain characteristic of SP.
      Examination of the spatial and temporal expression pattern of cSP gene revealed
      that, during embryogenesis, cSP was expressed in lumina epithelial cells of the
      proventriculus, gizzard, small intestine, and lung, but not the esophagus. In the
      proventriculus, cSP mRNA was first detected on day 8 of incubation and was
      localized to differentiated luminal epithelial cells. By using cSP as a molecular
      marker, the effects of mesenchyme on the differentiation of epithelium were
      analyzed in vitro. On the basis of these data, a model is presented concerning
      the differentiation of proventricular epithelium.

PMID- 9783478
TI  - A protein of the basal lamina of the sea urchin embryo.
AB  - The purification, biochemical characterization and functional features of a novel
      extracellular matrix protein are described. This protein is a component of the
      basal lamina found in embryos from the sea urchin species Paracentrotus lividus
      and Hemicentrotus pulcherrimus. The protein has been named Pl-200K or Hp-200K,
      respectively, because of the species from which it was isolated and its apparent
      molecular weight in SDS-PAGE under reducing conditions. It has been purified from
      unfertilized eggs where it is found packed within cytoplasmic granules, and has
      different binding affinities to type I collagen and heparin, as assessed by
      affinity chromatography columns. By indirect immunofluorescence experiments it
      was shown that, upon fertilization, the protein becomes extracellular, polarized
      at the basal surface of ectoderm cells, and on the surface of primary mesenchyme
      cells at the blastula and gastrula stages. The protein serves as an adhesive
      substrate, as shown by an in vitro binding assay where cells dissociated from
      blastula embryos were settled on 200K protein-coated substrates. To examine the
      involvement of the protein in morphogenesis of sea urchin embryo, early blastula
      embryos were microinjected with anti-200K Fab fragments and further development
      was followed. When control embryos reached the pluteus stage, microinjected
      embryos showed severe abnormalities in arms and skeleton elongation and
      patterning. On the basis of current results, it was proposed that 200K protein is
      involved in the regulation of sea urchin embryo skeletogenesis.

PMID- 9783480
TI  - Unequal divisions at the third cleavage increase the number of primary mesenchyme
      cells in sea urchin embryos.
AB  - To clarify the distribution and behavior of the maternal factors that direct the
      differentiation of primary mesenchyme cells (PMC) in sea urchin embryos, unequal
      division was induced at the third cleavage with the treatment of dinitro-phenol
      (DNP), and the numbers of differentiated PMC were examined. The most surprising
      finding was that the number of PMC was considerably increased in some of the DNP
      treated embryos. This increase n the number of PMC was suggested to be closely
      related to the size of the precocious micromeres formed at the 8-cell stage. By
      measuring both the size of the precocious micromeres and the number of PMC in
      individual embryos, it was suggested that almost all the descendants of the
      precocious micromeres differentiated into PMC, if the volume was less than 26 pL
      (about three times the volume of normal micromeres). Cell tracing experiments
      ascertained that precocious micromeres with small volumes behave just like
      micromeres formed at the fourth cleavage in normal embryos. The obtained results
      indicated that the maternal factors present in sea urchin embryos can direct, at
      least, more than three times the number of PMC, and that the number of cell
      divisions of the PMC lineage is not strictly regulated.

PMID- 9783481
TI  - Expression of hindlimb abnormalities under rearing temperature effects during the
      larval development of the salamander Pleurodeles waltl (urodele amphibian).
AB  - Anomalie m.p. is a spontaneous and heritable hindlimb abnormality described
      earlier. Twenty years later, Pleurodeles waltl larvae from the strain bearing
      anomalie m.p. and reared at room temperature or at 30 degrees C, expressed
      abnormalities (ectrodactylia, hemimelia, ectromelia). A morphological study of
      all the hindlimbs and an analysis of the hindlimb skeleton of samples from the
      experimental animals confirmed that most of the skeletal malformations were
      identical to those previously reported and affected the disto-proximal and
      prepostaxial pattern of the hindlimb. Analysis of the effects of rearing
      temperature on the expression of anomalie m.p. showed that the effects varied
      according to the developmental period at which the heat treatment was applied;
      the sooner the heat treatment began, the more numerous and more various were the
      degrees of severity of the malformations. Moreover, heat treatment induced the
      expression of two additional malformations not yet described: the first one,
      named 'reversed knee joint', was characterized by a reversal of the knee joint,
      and the second one, named 'twisted foot', by a downward twisting of the foot. The
      epigenetic effects of rearing at 30 degrees C on hindlimb development are
      discussed with regard to the differentiation or patterning.

PMID- 9783479
TI  - Proximal cis-regulatory elements of sea urchin arylsulfatase gene.
AB  - Expression of the arylsulfatase (HpArs) gene in the sea urchin, Hemicentrotus
      pulcherrimus, is regulated in spatially, as well as temporally, during
      development. To address the cis-regulatory elements involved in this regulation,
      we performed reporter assays using variously deleted or mutated promoter and
      regulatory elements of the HpArs gene, accompanied by gel mobility shift assay
      and foot printing. Results show that two regions, PU1 (-72 b.p. to -56 b.p.),
      which is similar to SpZ12-1 and/or Oct-1 motif, and the PD1 site (+133 b.p. to
      +142 b.p.), which is homologous to the binding sites of Rel family transcription
      factors and/or AGIE-BP1, are related to the regulation of expression of the HpArs
      gene. Furthermore, an HpArs enhancer element called C15, which is located 3 kb.p.
      downstream from the transcription start site, activates the HpArs promoter. We
      also report that the enhancer activity of the C15 fragment was mediated by
      elements, PU1 and PD1.

PMID- 9783482
TI  - Coelomic pouch formation in reconstructing embryos of the starfish Asterina
      pectinifera.
AB  - The morphogenetic processes of coelomic pouch (CP) formation in starfish embryos
      that were experimentally dissociated and induced to undergo reconstruction were
      studied. An analysis of these embryos randomly chosen from several cultures
      showed that CP always form on either side of the esophagus, even though the CP
      formation can differ in timing of initiation and duration, and can vary in number
      and size from embryo to embryo. Successive observations of CP formation in living
      embryos revealed two distinct sequences of CP development that were accompanied
      by different appearances of the blastocoele. These processes were named
      'enterocoelic-like' and 'schizocoelic-like' CP formation. The former resembled
      normal development and occurred in embryos with a transparent blastocoele. The
      latter was characterized by the aggregation and epithelialization of mesenchyme
      like cells on either side of the esophagus and was observed in embryos possessing
      a cloudy blastocoele. In a few embryos, both types of CP formation were seen in
      the same individual ('mosaic type' CP formation). Thick sections of embryos
      possessing a cloudy blastocoele revealed that aggregates of mesenchyme-like cells
      undergoing CP formation directly contact the developing esophagus. Together,
      these data demonstrate flexibility in the morphogenetic processes that regulate
      CP formation, and suggest that positional cues in the esophagus regulate the
      placement of CP.

PMID- 9783483
TI  - Cardiovascular risk factors in the elderly.
AB  - Although a number of risk factors for cardiovascular morbidity and mortality have
      been identified in young and middle-aged adults, their prevalence and importance
      are less known in the elderly. Elderly people have a risk profile different from
      that of younger subjects, but representative data on risk factors for
      cardiovascular disease in the elderly are difficult to find in the literature.
      Some typical 'major' risk factors, like blood pressure (BP), total cholesterol or
      left ventricular hypertrophy, do not have a clear predictive role for
      cardiovascular mortality in the elderly, especially in the extreme ages, while
      risk indicators usually labelled as 'minor' (serum uric acid, ventilatory
      function or proteinuria), do have a strong predictive value in these individuals.
      This must be taken into account when evaluating the cumulative risk of the
      elderly, in order to avoid overtreatment of subjects with mildly elevated BP or
      cholesterol.

PMID- 9783485
TI  - The epidemiology of the association between hypertension and menopause.
AB  - Menopause is a normal aging phenomenon in women and consists of the gradual
      transition from the reproductive to the non-reproductive phase of life. The
      median age at the menopause is currently around 50 years. As a result of the
      increasing life expectancy in the first and second worlds, many women will be
      postmenopausal for over one-third of their lives. The influence of menopause per
      se on blood pressure remains uncertain. Recent experimental and epidemiological
      evidence supports the hypothesis that oestrogen deficiency may induce endothelial
      and vascular dysfunction and potentiate the age-related increase in systolic
      pressure, possibly as a consequence of a reduced compliance of the large
      arteries. However, the latter hypothesis requires further investigation.

PMID- 9783484
TI  - Influence of aging on arterial compliance.
AB  - With aging, pulse pressure increases. A high pulse pressure has been recognised
      as an important cardiovascular risk factor. The increase in pulse pressure with
      aging is mainly due to a decrease in large artery compliance. Compliance and
      distensibility are large artery wall properties. Compliance is the buffering
      capacity of the vessel. Distensibility reflects much more the elasticity of the
      artery. Compliance is related to distensibility and arterial diameter. These
      large artery wall properties can be measured non-invasively using new echo
      tracking techniques. With these techniques it has been shown that the elasticity
      (distensibility) and the buffering capacity (compliance) of the common carotid
      artery is decreasing with aging, while diameter of the artery increases. This
      increase in diameter might be a compensating mechanism to limit the decrease in
      compliance. There are indications that the effect of aging on large artery wall
      properties may not be similar at all vascular territories. A decrease in
      compliance leads to a high pulse pressure and isolated systolic hypertension. The
      drug of choice for the treatment of isolated systolic hypertension should
      increase large artery compliance with no, or only minor effect on resistance
      vessels. This would lead to a decrease in pulse pressure without decreasing mean
      blood pressure. As a result, systolic but not diastolic blood pressure decreases.
      It appears that nitrates better than other anti-hypertensive drugs can decrease
      pulse pressure. They therefore have been advocated for the treatment of isolated
      systolic hypertension.

PMID- 9783486
TI  - The heart in the hypertensive elderly.
AB  - Left ventricular (LV) mass progressively increases throughout life, reaching its
      greatest magnitude in senescence. In the normotensive elderly, left ventricular
      hypertrophy (LVH) is mostly a consequence of a degenerative process in connective
      tissue. In hypertensive patients, LVH results from an increase in muscle mass and
      fibrotic tissue. LVH by echocardiographic criteria can be found in up to 50% of
      elderly patients with hypertension. Although associated with aging, LVH is
      associated with a higher rate of non-fatal and fatal cardiovascular events. Even
      in the absence of coronary stenosis, LVH is associated with reduced coronary
      reserve, increased number of arrhythmias and progressive deterioration in LV
      function. Conceivably, an increase in interstitial fibrosis and cross-linking
      collagen in the senescent heart is responsible for an increase in myocardial
      stiffness and diastolic abnormalities. Regression of LVH has been demonstrated
      not only to improve left ventricular filling and coronary reserve but also to
      diminish cardiac arrhythmias. Although few studies have demonstrated that the
      reduction of LV mass is associated with better cardiovascular prognosis, it seems
      reasonable to consider it a goal of antihypertensive therapy. Of all anti
      hypertensive agents, angiotensin-converting-enzyme inhibitors seem to be the most
      powerful in reducing LV mass.

PMID- 9783487
TI  - Renal function in treated and untreated hypertension.
AB  - There is now increasing evidence that essential hypertension is a serious risk
      factor for renal insufficiency. It has been known for many years that malignant
      essential hypertension rapidly causes deterioration of kidney function. This can
      be prevented by treatment with anti-hypertensive drugs. Mild-to-moderate
      essential hypertension causes significant renal function impairment only after a
      number of years. There are now data suggesting that the decline of renal function
      caused by mild-to-moderate essential hypertension can be prevented by anti
      hypertensive treatment. In recent years, it has been demonstrated that anti
      hypertensive drugs have a beneficial effect on the progression of renal
      insufficiency in patients with diabetic nephropathy and in chronic
      glomerulonephritis. In these situations, ACE inhibitors appear to be superior to
      other classes of anti-hypertensive drugs.

PMID- 9783488
TI  - Secondary hypertension in the elderly.
AB  - This paper discusses the most significant aspects of secondary hypertension in
      older patients against the background of a rising proportion of elderly in the
      hypertensive population. Renal artery stenosis and pheochromocytoma are singled
      out as those causes of secondary hypertension which appear to be related to older
      age. The available data relevant to epidemiology of these conditions and age
      dependent clinical characteristics are reviewed. Preservation of renal function
      in the elderly with renal artery stenosis is underlined as an important goal of
      therapy with revascularising techniques. It is proposed that screening for renal
      artery stenosis and pheochromocytoma may be equally important in the elderly as
      in the younger hypertensive patient.

PMID- 9783489
TI  - Which elderly patients should be considered for anti-hypertensive treatment? An
      evidence-based approach.
AB  - BACKGROUND: The evidence-based approach to medical care involves the explicit use
      of evidence on the magnitude of the effects of interventions to inform diagnostic
      and treatment decisions. This article critiques current mainstream guidelines on
      the management of hypertension in the elderly (aged 60 years and over) and
      presents an alternative evidence-based approach. METHODS: Three major national
      and international guidelines for the management of hypertension from the United
      Kingdom (UK), the United States (US) and from a joint World Health
      Organisation/International Society of Hypertension (WHO/ISH) Working Party were
      appraised and the evidence on which they were based was reviewed. The relevant
      evidence was also assessed to determine the likely magnitude of risks and
      benefits of anti-hypertensive treatment in older people and an alternative
      approach to making treatment decisions, based on the New Zealand guidelines for
      the management of hypertension, is described. RESULTS: Hypertension management
      guidelines from the UK, US and WHO/ISH made similar recommendations about which
      elderly patients should be treated, although there were some ambiguities in their
      advice. Treatment recommendations were based primarily on blood pressure levels
      which were set at about 160 mm Hg systolic and/or 90 mm Hg diastolic. The
      threshold levels were based mainly on the cut-off blood pressure levels used in
      randomised trials of anti-hypertensive drug treatment, rather than the estimated
      magnitude of treatment benefit. Each of the guidelines acknowledged the important
      effect of associated cardiovascular disease (CVD) risk factors on the likely
      benefits of treatment, but did not expand on the magnitude of this effect. No
      patient-specific estimates of the likely absolute benefits of treatment were
      provided in any of the guidelines. In contrast the New Zealand guidelines for the
      management of hypertension recommend the use of explicit estimates of absolute
      CVD risks and benefits to inform treatment decisions. They were designed to
      provide practitioners with estimates of the likely absolute risk of CVD in
      patients with different risk factor profiles and with estimates of the absolute
      benefits of treatment. The New Zealand guidelines recommend that drug treatment
      be considered in patients with a 5-year risk of CVD of about 10-15% or more;
      approximately 25 patients with a 10-15% risk would require treatment for 5 years
      to prevent one CVD event. As elderly patients are generally at higher absolute
      CVD risk than younger people, the New Zealand recommendation give priority to the
      treatment of older patients. In order to take account of differences in life
      expectancy and the medical costs of caring for elderly people, absolute risk
      based guidelines can be improved by incorporating potential years of life gained
      from treatment and the cost-effectiveness of treatment expressed as $/quality
      adjusted life years gained. Preliminary analyses indicate that the cost
      effectiveness of treatment is generally greatest in patients in their 60s and
      early 70s. Treatment in younger people is not usually very cost-effective because
      of their low absolute risk of CVD and the cost-effectiveness of treatment in
      people over about 75 years declines because of the increasing cost of non-CVD
      morbidity. CONCLUSIONS: The explicit assessment of absolute CVD risks and likely
      treatment benefits in patients with hypertension can usefully inform treatment
      decisions and provide a more rational basis for initiating therapy than blood
      pressure levels alone. This approach highlights the generally greater CVD risk
      and potential treatment benefits in older compared with younger hypertensive
      patients. The absolute risk-based approach can be further enhanced by providing
      decision makers with patient-specific data on the potential life years gained
      from treatment and its cost-effectiveness. (ABSTRACT TRUNCATED)

PMID- 9783490
TI  - Tailoring anti-hypertensive treatment in the elderly.
AB  - The treatment of hypertension in the elderly has to take into account co-existing
      pathology. However, the benefit from treatment are large in terms owing to the
      frequency of cardiovascular events in the elderly. The benefits observed in
      randomised controlled trials are reviewed together with the adverse effects of
      the individual treatments. The optimal use of anti-hypertensive treatment is
      considered in light of any concomitant disease; for example beta-blockers or
      calcium channel blockers when angina is present and the avoidance of diuretics in
      the presence of gout. Important hazardous drug interactions are also discussed.
      It is concluded that diuretics are still the first choice in uncomplicated
      hypertension and the least expensive. However the place of anti-hypertensive
      treatment is not established in those over the age of 80 years.

PMID- 9783491
TI  - Isolated systolic hypertension: pathophysiology, consequences and therapeutic
      benefits.
AB  - During recent decades the importance of perceiving isolated systolic hypertension
      (ISH) in cardiovascular pathophysiology has been changed from a benign condition
      to the major cardiovascular risk factor. Aging is per se associated with the
      deterioration in arterial compliance through both structural and functional
      changes in large arteries which mainly involves the intima and media. The
      observed changes result in a decrease of the lumen-to-wall ratio, the overall
      lumen cross-sectional area and an increase of arterial stiffness which especially
      involve the aorta and other elastic arteries. In addition to the structural
      changes in vessel walls, aging is associated with certain functional changes such
      as an increase in sympathetic system activity probably due to the age-related
      decreased sensitivity of beta-receptors. While the function of arterial wall
      alpha-receptors remains intact, in elderly subjects a shift towards arterial
      vasoconstriction can be observed. In many of the published studies the definition
      of ISH was based on the criterion 160/95 mm Hg or 160/90 mm Hg while in
      recognition of the high risk associated with systolic blood pressure (SBP) the
      WHO/ISH guidelines and Report of the Sixth Joint National Committee on
      Hypertension indicated that ISH should be diagnosed with SBP as > or =140 mm Hg
      and diastolic BP (DBP) as <90 mm Hg. Thus the setting down of normal values of
      SBP will lead to an earlier diagnosis and treatment of ISH. Several prospective
      studies, such as the US Hypertension Detection and Follow-up Programme, confirmed
      this and the Multiple Risk Factor Intervention Trial demonstrated that for any
      given level of DBP, higher SBP was associated with an increase in cardiovascular
      risk. Moreover, data from the Framingham Study show that ISH was associated not
      only with increased mortality but also cardiovascular morbidity. Risk of non
      fatal stroke and myocardial infarction was increased three and two-times
      respectively in the presence of ISH. Three major up-to-date studies that included
      patients with ISH have been published. In concordance to the previously published
      SHEP and MCR trials, the most recent, the Systolic Hypertension in the Elderly
      Trial (SYST-EUR), demonstrated that active treatment significantly reduces the
      risk of stroke and all fatal and non-fatal cardiac end-points, including sudden
      death. Of note, these benefits were demonstrated with new anti-hypertensive
      classes such as dihydropiridyne calcium channel blocker (nitrendipine) and the
      angiotensin-converting enzyme inhibitor (enalapril). The necessity to carefully
      balance the benefits and risks of anti-hypertensive therapy in the elderly
      indicates that patients with suspected ISH should undergo careful BP measurements
      on at least three different occasions before the diagnosis is established and an
      orthostatic reaction should be evaluated. If non-pharmacological procedures fail,
      drug therapy should be considered, especially in elderly patients with a SBP over
      160 mm Hg, since their risk of complications is markedly higher. Pharmacological
      treatment should also be strongly considered in patients with a SBP between 140
      and 160 mm Hg with such concomitant cardiovascular risk factors as diabetes,
      angina pectoris, and left ventricular hypertrophy. The drug regimen should be
      simple, starting with a low dose of a single drug that is titrated slowly. The
      selection of the first-line anti-hypertensive agent should be based on a careful
      assessment of pathophysiological and clinical parameters in each individual
      geriatric patient.

PMID- 9783492
TI  - PROGRESS: Perindopril pROtection aGainst REcurrent Stroke Study: status in March
      1997. PROGRESS Management Committee.
AB  - MAIN OBJECTIVE: The study has been designed to assess the efficacy of blood
      pressure (BP) reduction in the prevention of stroke in patients with a history of
      ischaemic stroke, haemorrhagic stroke, or transient ischaemic attack. STUDY
      DESIGN: A randomised, double-blind, placebo-controlled, international,
      multicentre trial of the angiotensin-converting enzyme (ACE) inhibitor
      perindopril, alone or in combination with the diuretic indapamide, in the
      secondary prevention of stroke and other major cardiovascular events.
      METHODOLOGY: A total of 6000 normotensive or hypertensive patients with a history
      of stroke or transient cerebral ischaemia within the previous 5 years will be
      included in the study. The study is being conducted in over 160 centres located
      in seven regions: Australia and New Zealand; The People's Republic of China;
      France and Belgium; Italy; Japan; Sweden; and the United Kingdom. The primary
      study outcome is the total number of strokes defined by WHO criteria. Secondary
      outcomes include fatal and disabling strokes, total number of cardiovascular
      events and deaths, cognitive function, disability, and dependency. A minimum of 4
      years' follow-up is planned. RESULTS: By 27 March 1997, 173 local clinical
      centres had been registered in seven regions. A total of 5268 patients (64% with
      a history of hypertension or baseline BPs above 95 mm Hg [diastolic] or 160 mm Hg
      [systolic]) had been randomly assigned to active treatment or placebo. After 6
      months' follow-up the difference in BP between treatment and control groups was
      10.2/4.5 mm Hg (systolic/diastolic). Sixty-three strokes (two fatal) and 20
      myocardial infarctions (four fatal) had been recorded. CONCLUSIONS: The viability
      of the study is now assured, with almost 90% of 6000 patients recruited. ACE
      therapy with perindopril is well tolerated in the studied population. The BP
      differences between control and treatment groups and the event rates recorded to
      date suggest that the study will achieve its primary objectives.

PMID- 9783493
TI  - Progression of asymmetric pattern of left ventricular hypertrophy in patients
      with hypertrophic cardiomyopathy accompanied by hypertension in the elderly.
AB  - OBJECTIVE: The aim of the study was to determine the potential influence of
      hypertension overlapping hypertrophic cardiomyopathy (HCM) on left ventricular
      hypertrophy (LVH) pattern. We compared the magnitude of LVH asymmetry between
      younger and older patients with HCM and concomitant hypertension. MATERIAL AND
      METHODS: We studied 18 patients (age range from 18 to 77 years) in whom HCM was
      accompanied by mild-to-moderate hypertension. Patients were subdivided into two
      groups: (I) <50 years of age (11 patients); and (II) >50 years of age (seven
      patients). The thickness of ventricular septum and posterior wall was assessed by
      M-mode echocardiography. The pattern of LVH was determined based on the value of
      ventricular septum/posterior wall thickness (VS/PW) ratio and LVMI was calculated
      according to Devereux formula. RESULTS: The more asymmetric LVH pattern was
      revealed in older HCM with hypertension patients than in younger patients (VS/PW
      thickness ratio 2.62 +/- 0.81 vs 1.58 +/- 0.56, P < 0.05). The LVMI was similar
      in both groups (210 + 87 vs 191 + 30 g/m2, P > 0.5). CONCLUSION: Asymmetric
      pattern of LVH aggravated with increasing age in HCM with hypertension patients
      while LVMI was comparable between younger and older patients. Thus, the primary
      myocardial disease, ie, HCM, so significantly determined the asymmetric LVH
      pattern with aging that coexistent hypertension was not a sufficiently strong
      stimulus to alter LVH pattern into a more concentric one in the elderly.

PMID- 9783494
TI  - The frequency and functional impact of hypertension overlapping on hypertrophic
      cardiomyopathy: comparison between older and younger patients.
AB  - BACKGROUND AND AIM: In a previous report, when hypertension (HT) overlapped on
      hypertrophic cardiomyopathy (HTHCM), the decreased survival rate was associated
      with higher NYHA classes. The study concerned only elderly patients and therefore
      we decided to extend it by: (1) assessment of the frequency and age-distribution
      of HTHCM in HCM population; and (2) the comparison of NYHA class between HTHCM
      and HCM both in younger and older patients. PATIENTS AND METHODS: We
      retrospectively viewed 123 HCM patients with regard to the presence of
      hypertension as a concomitant disease. The HTHCM and HCM patients were compared
      with regard to NYHA functional classes within younger (<50 years of age) and
      older (>50 years of age) subgroups. RESULTS: Of the 123 HCM patients, 24 (19.5%)
      had associated hypertension. Among younger patients, 15.7% had concomitant
      hypertension, while in older patients the percentage of HTHCM significantly
      increased to 38%. In younger patients, the mean values of the NYHA class were
      significantly higher in HTHCM in comparison to HCM patients (2.19 +/- 0.37 vs
      1.94 +/- 0.56, P < 0.05), whereas in the older patients, the mean values of NYHA
      class were comparable between HTHCM and HCM patients (2.13 +/- 0.33 vs 2.23 +/-
      0.42, P > 0.05). CONCLUSION: Hypertension associated with HCM is not rare in
      young patients, and this coincidence significantly increases in older patients.
      Hypertension overlapping on HCM additionally deteriorates functional status in
      younger patients whereas in the older patients NYHA class the difference between
      HTHCM and HCM narrows and becomes insignificant.

PMID- 9783496
TI  - Hypertension in the elderly with advanced locomotive disability.
AB  - The aim of the study was to estimate the frequency of hypertension among the
      elderly with advanced locomotive disability and to evaluate the difficulties with
      the therapy of hypertension in this group of patients. The study was carried out
      on the base of 100 persons over 60 years old with advanced locomotive disability
      (groups III and IV according to Piotrowski's classification) selected from about
      2000 community-dwelling geriatric patients. The clinical examination (with
      elements of comprehensive geriatric assessment) and estimation of arterial
      pressure was made at each patient's home. Among 100 examined probands 43 had
      normal arterial pressure and the remaining 57 had different forms of
      hypertension. This group comprised of 84% patients treated with hypotensive
      drugs, 9% patients without any anti-hypertensive therapy, and 7% patients
      hypertension were not found earlier. A similar frequency of occurrence of
      hypertension is given by Kocemba (53.1%) and by the National Health and Nutrition
      Examination Survey (64.3%). Therapy of hypertension in disabled elderly people
      was ineffective in most of the studied hypertensive patients (71%).

PMID- 9783497
TI  - Twenty-four hour ambulatory blood pressure monitoring in young and elderly
      hypertensive subjects.
AB  - The aim of our study was to compare blood pressure (BP) measured by 24-h
      ambulatory monitoring in young and elderly hypertensives and to find a dependency
      between left ventricular mass (LVM) and different pressure ratios. We also
      estimated the calcium ionized concentration and serum lipids in all subjects. Two
      hypertensive groups divided accordingly by age were studied. The duration of
      hypertension was similar in both groups. The Oxford Medilog ABP was used for the
      arterial BP recordings. Mean arterial BP, BP loads and night/day mean arterial
      pressure ratio were evaluated. In both groups left ventricular mass index (LVMI)
      were calculated. The serum calcium ionized concentration (Ca++) was estimated and
      serum lipids were determined. We found 10 non-dippers in the young group and
      seven non-dippers in the elderly hypertensives. LVM and LVMI were comparable in
      both groups. We showed the correlation of the nocturnal mean arterial pressure
      with LVM in elderly hypertensives and the dependency of nocturnal BP load with
      LVM in this group. Serum calcium ionized concentration was significantly
      decreased in the elderly patients, and LDL-cholesterol was significantly higher
      in this group. We found a negative correlation between serum calcium and
      triglycerides in young and elderly hypertensives. We found more non-dippers in
      the young hypertensives and a positive correlation between LVM and nocturnal mean
      arterial pressure and nocturnal BP load in elderly subjects. These results
      suggest the cardiovascular prognosis is not good in both groups. The prognosis in
      elderly hypertensives was also worsened by the low serum calcium ionized and high
      LDL-cholesterol concentrations.

PMID- 9783495
TI  - Urinary excretion of Tamm-Horsfall protein in normotensive and hypertensive
      elderly patients.
AB  - Tamm-Horsfall protein (THP) is a glycoprotein that is exclusively produced by the
      kidney in the thick ascending limb of Henle's loop (TAHL). Disturbances of TAHL
      function are associated with decreased urinary THP excretion. It is well known
      that renal function declines with advancing age. Moreover, it is suggested that
      THP may play a role in the pathophysiology of hypertension. The aim of this study
      was to assess urinary excretion of THP (U-THP) in healthy and hypertensive
      elderly patients. Fifteen young healthy subjects (YHS), 15 young hypertensive
      patients (YHT), 15 older normotensive (>60 years) subjects (OHS) and 31 older
      (>60 years) hypertensive patients (OHT) were examined. In all subjects 24-h
      urinary volume (UV), U-THP and creatinine (U-Cr), specific gravity of urine (U
      SG), serum creatinine (S-Cr), and mean arterial pressure (MAP) were assessed. THP
      urinary excretion was significantly decreased in normotensive elderly patients,
      but not in hypertensive ones. Higher U-THP in the elderly hypertensive as
      compared with the elderly normotensive patients seems to be more the consequence
      than the cause of arterial hypertension.

PMID- 9783498
TI  - Bisoprolol in the treatment of hypertension in the elderly.
AB  - The aim of the study was to examine the hypotensive efficacy and tolerance of
      bisoprolol in elderly patients. Sixty patients (40 <65 years and 20 >65 years)
      with mild-to-moderate essential hypertension (diastolic blood pressure (DBP)
      between 95 and 109 mm Hg) were included in the study. After a 2-week run-in
      period on placebo, patients began bisoprolol therapy (5 mg/d) for 12 weeks. After
      4 weeks the dose was increased to 10 mg/d in those with a DBP > or =95 mm Hg.
      Additionally, in 10 patients over 65 years old, 24-h ambulatory BP monitoring
      (ABPM) was performed, after placebo and after bisoprolol (5 mg) administration.
      The hypotensive efficacy of bisoprolol in the elderly and younger patients was
      similar. Before and after treatment the mean difference of systolic BP (SBP) was
      19.6 +/- 12.5 mm Hg and DBP 9.6 +/- 6.2 mm Hg in the younger patients and 16.1 +/
      13.6 mmHg and 9.5 +/- 6.0 mmHg in the elderly patients. Bisoprolol produced a
      similar reduction in heart rate (23.1% vs 17.1%) in the estimated groups. The
      tolerance of bisoprolol was good in both groups. There were no significant
      differences in adverse drug reactions between the groups.

PMID- 9783499
TI  - Obesity and blood pressure in the elderly free-living population.
AB  - OBJECTIVE: The aim of presented analysis was to determine the relationship
      between blood pressure (BP) and different indices of obesity in the elderly free
      living population. DESIGN AND METHODS: In 317 inhabitants of the randomly chosen
      area of Cracow (70 years old and older) who could come to the out-patient clinic
      for an interview, BP, weight and height were taken. Body mass index (BMI) was
      used to classify the population into lean (BMI < 25 kg/m2), overweight (25 < or =
      BMI < 30 kg/m2) and obese (BMI > or = 30 kg/m2) subjects. In order to separate
      the effect of adipose tissue and lean body mass, weight of total adipose tissue
      (AT) and lean body mass (LBM) were calculated according to the anthropometric CT
      calibrated equations. RESULTS: Obese patients had a significantly higher systolic
      BP (SBP) when compared with lean subjects (respectively SBP [mm Hg] 175.7 +/-
      27.5 vs 161.8 +/- 21.8), and higher diastolic BP (DBP) [mm Hg] in comparison with
      both other groups (obese: 93.7 +/- 12.4 vs lean: 85.34 +/- 10.6, overweight:
      87.15 +/- 12.73). The relationship between systolic and diastolic BP, and weight
      (respectively for SBP: r = 0.256, DBP: r = 0.216), BMI (SBP: r = 0.261, DBP: r =
      0.216) and AT (SBP r = 0.269, DBP r = 0.22, P < 0.01) was found only in women but
      not in men. CONCLUSIONS: Our results suggest that in the elderly the importance
      of obesity in the pathogenesis of hypertension depends partially on gender and it
      may be essential in women but not in men.

PMID- 9783500
TI  - JNC-VI: a view from the United Kingdom.

PMID- 9783501
TI  - The Appropriate Blood Pressure Control in Diabetes (ABCD) Trial.

PMID- 9783502
TI  - The incidence of regurgitation during cardiopulmonary resuscitation: a comparison
      between the bag valve mask and laryngeal mask airway.
AB  - The risk of gastric regurgitation and subsequent pulmonary aspiration is a
      recognised complication of cardiac arrest--a risk which may be further increased
      by the resuscitative procedure itself. The purpose of this study was to compare
      the incidence of gastric regurgitation between the bag valve mask (BVM) and
      laryngeal mask airway (LMA). The resuscitation data collection forms of 996
      patients who underwent in-hospital cardiopulmonary resuscitation over a 3.5 year
      period were reviewed. Of these, 199 patients were excluded from the study because
      there was no airway management involving a BVM or LMA. The incidence and timing
      of regurgitation was studied in the remaining 797 patients. Regurgitation was
      recorded to have occurred at some stage in 180 of these patients (22.6%).
      However, 84 regurgitated prior to CPR (46.7% of those patients who regurgitated).
      These patients were excluded from further analysis as regurgitation could not
      have been affected by any form of ventilation. Of the remaining 713 patients, BVM
      ventilation was used in 636 cases. In 170 of these the LMA was also used
      following the BVM. Where the patient was ventilated with the BVM alone or BVM
      followed by ETT the incidence of regurgitation during CPR was 12.4%. The LMA was
      used during resuscitation in 256 cases of which 170 had BVM ventilation prior to
      the LMA. Where the patient was ventilated with the LMA alone or LMA followed by
      ETT the incidence of regurgitation during CPR was 3.5%. The study confirms
      experience reported in earlier studies that when an LMA is used as a first line
      airway device, regurgitation is relatively uncommon.

PMID- 9783503
TI  - A comparison of standard and a modified method of two resuscitator adult
      cardiopulmonary resuscitation: description of a new system for research into
      advanced life support skills.
AB  - The study compares two methods of Advanced Life Support by a pair of
      resuscitators using a bag-valve-mask (BVM) technique. Standard two resuscitator
      cardiopulmonary resuscitation (CPR) was compared with a modified method of two
      resuscitator CPR. During the modified CPR one resuscitator held the face mask
      while the other resuscitator alternates between squeezing the self inflating bag
      and performing simulated cardiac compressions. Standard CPR was performed at a
      ventilation:compression ratio of 1:5 while modified CPR was performed at a
      ventilation:compression ratio of 2:15. Comparisons were made during induction of
      anaesthesia in 30 ASA I and II patients. Modified CPR produced a greater tidal
      volume (TV) (P < 0.001), a slower respiratory rate (RR) (P < 0.001) and a faster
      compression rate (CR) (P < 0.01) (means with (S.D.): modified CPR: TV 990 (220)
      ml, RR 6 (1) min(-1), CR 82 (8) min(-1); standard CPR: TV 570 (190) ml, RR 10 (2)
      min(-1), CR 65 (11) min(-1)). A new method for the simultaneous computerised
      recording of simulated cardiac compressions together with mask pressure and
      expired gas composition in anaesthetised patients is described.

PMID- 9783505
TI  - Splanchnic and renal blood flow after cardiopulmonary resuscitation with
      epinephrine and vasopressin in pigs.
AB  - In laboratory investigations, vasopressin given during CPR resulted in improved
      vital organ blood flow when compared with epinephrine. Given the profound and
      long lasting vasopressor effects of vasopressin, we tested the hypothesis that
      vasopressin given during CPR would result in renal and splanchnic hypoperfusion
      in the post-resuscitation period when compared with epinephrine. After 4 min of
      ventricular fibrillation, 16 pigs were randomly assigned to receive either 0.045
      mg x kg(-1) epinephrine or 0.4 U X kg(-1) vasopressin before defibrillation.
      Splanchnic and renal blood flow were measured 30, 90, and 240 min after
      restoration of spontaneous circulation (ROSC) in the epinephrine and vasopressin
      groups and in a control group of eight pigs using radiolabeled microspheres.
      Hepatic blood flow was measured before arrest and 30, 90, and 240 min after ROSC
      by means of indocyanine green infusion. Thirty minutes after ROSC, renal and
      adrenal blood flow were significantly lower in the vasopressin group (300 [273
      334] and 256 [170-284] ml X min(-1) x 100 g(-1)) (median and 25th and 75th
      percentile) as compared with the epinephrine group (370 [346-429] and 360 [326
      420] ml x min(-1) x 100 g(-1); P < 0.05). Pancreatic, intestinal, and hepatic
      blood flow were not significantly different in animals after receiving
      epinephrine or vasopressin. In comparison to epinephrine, vasopressin given
      during cardiac arrest impairs renal and adrenal perfusion temporarily but does
      not lead to intestinal or hepatic hypoperfusion in the post-resuscitation phase.

PMID- 9783504
TI  - Vasopressin combined with nitroglycerin increases endocardial perfusion during
      cardiopulmonary resuscitation in pigs.
AB  - Although vasopressin increases vital organ blood flow during cardiopulmonary
      resuscitation (CPR), endocardial perfusion remains suboptimal. This study was
      designed to assess the effects of vasopressin versus a combination of vasopressin
      and nitroglycerin on vital organ blood flow in a porcine model of CPR. After 4
      min of cardiac arrest, and 3 min of closed-chest compressions, 14 animals were
      randomly treated with either 0.4 U/kg vasopressin (n = 7) or 0.4 U/kg vasopressin
      combined with 5 microg/kg nitroglycerin (n = 7). Coronary and cerebral perfusion
      pressure as well as left ventricular myocardial blood flow was comparable between
      groups throughout the experiment. Ninety seconds after drug administration,
      vasopressin combined with nitroglycerin resulted in comparison with vasopressin
      alone in significantly higher mean (+/- standard error of the mean) left
      ventricular endocardial blood flow (78+/-7 vs 51+/-5 ml x min(-1) x 100 g(-1); P
      < 0.05), and a significantly higher endocardial/epicardial perfusion ratio
      (0.93+/-0.09 vs 0.57+/-0.06; P < 0.05). Seven of seven animals in the vasopressin
      group, and four of seven animals in the vasopressin and nitroglycerin group (NS)
      were resuscitated successfully and survived the 2-h observation period. We
      conclude that, when compared with vasopressin therapy alone, combined vasopressin
      and nitroglycerin improved endocardial perfusion significantly immediately after
      drug administration during CPR.

PMID- 9783506
TI  - Labetalol-induced hypotension decreases blood loss during uncontrolled
      hemorrhage.
AB  - In a model of uncontrolled hemorrhagic hypotension (UCHH) in rats, we examined
      whether blood loss or blood chemistry were affected by (1) deliberate, controlled
      hypotension induced with labetalol (L) or sodium nitroprusside (SNP) and (2)
      intravenous (iv) fluid therapy. Two hours of UCHH was induced by resecting the
      distal 25% of the tail. L or SNP was infused with the aim of decreasing MAP to 50
      mmHg. In the groups receiving iv fluid, 3 ml of 0.9% saline was given for each 1
      ml of blood loss. L decreased blood loss (2.8+/-2.0 and 3.0+/-1.9 ml,
      respectively, in the groups not receiving and receiving iv fluid) compared to the
      groups not given hypotensive drugs (6.3+/-4.1 and 13.5+/-6.6 ml). SNP did not
      decrease blood loss (5.7+/-4.7 and 11.0+/-6.2 ml), increased serum potassium
      (5.0+/-0.6 and 5.8+/-0.4 mEq l(-1)), and with accompanying iv fluid
      administration decreased hematocrit, worsened acidosis, and increased mortality.
      In this model of 2 h of UCHH in rats, hypotension to MAP of 50 mmHg with L but
      not with SNP decreased blood loss.

PMID- 9783507
TI  - A computer model of gas exchange during cardiopulmonary resuscitation.
AB  - This paper presents a computer model of gas exchange during cardiopulmonary
      resuscitation (CPR) that permits independent adjustment of inspired air content
      (16% O2 and 4.5% CO2 present in mouth-to-mouth (MTM) ventilation or ambient air),
      shunt, deadspace, diffusion impairment, cardiac output, and ventilation. The
      model contains 15500 acini, each with its own blood supply. Gas exchange occurs
      at each perfused and ventilated acinus. Arterial P(O2) and P(CO2) are calculated
      from the summed arterial blood flow using standard formulae. The model and
      simulations show that MTM ventilation provides inadequate oxygenation when the
      victim is at high altitude or has diffusion impairment. They also show that
      analysis of inspired and expired gas concentrations to measure gas exchange
      primarily measures wash in and wash out of gas when cardiac output is low and
      that this explains the negative oxygen consumption and carbon dioxide production
      measured in a previous study.

PMID- 9783508
TI  - Successful resuscitation using aminophylline in refractory cardiac arrest with
      asystole.
AB  - Adenosine antagonists may have therapeutic potential in cardiopulmonary
      resuscitation. Aminophylline, a widely available adenosine antagonist, is not
      included in the Guidelines for Advanced Life Support by the European
      Resuscitation Council or the American Heart Association. This report addresses a
      case of out-of-hospital cardiac arrest caused by inferior wall myocardial
      infarction in which effective circulation was restored subsequent to
      aminophylline administration, after prolonged conventional resuscitation had
      resulted in asystole.

PMID- 9783509
TI  - Partial transsection of the neonatal trachea.
AB  - This report describes an unusual case of partial transsection of the neonatal
      trachea after intubation. Mucosal injury led to the formation of a balloon
      shaped, air-filled cyst that did not allow ventilation of the airways either via
      a tracheal tube or with a face mask. Several minutes after death, the cyst had
      collapsed and bag and mask ventilation produced adequate chest movements.

PMID- 9783510
TI  - Prehospital thrombolytic treatment of massive pulmonary embolism with reteplase
      during cardiopulmonary resuscitation.
AB  - A 52-year-old previously healthy man experienced acute severe dyspnoea after
      suffering from gastroenteritis for 3 days. After arrival of the ambulance,
      cardiac arrest with an initial rhythm of electro mechanical dissociation
      occurred. Circulation was restored after 10 min of cardiopulmonary resuscitation
      but soon cardiac arrest reoccurred. Based on a strong clinical suspicion of
      massive pulmonary embolism, thrombolytic treatment with heparin 5000 IU and
      reteplase 20 U, given as single boluses and heparin was continued as an infusion
      1000 IU h(-1). After 7 min of continued resuscitation, circulation was restored
      and after 40 min the vital functions began to stabilize, thus indicating
      pulmonary reperfusion. The diagnosis of pulmonary embolism was confirmed by a
      ventilation-perfusion scan and by spiral computerised tomography. The patient was
      discharged from intensive care after 2 days with a cerebral performance category
      I. Based on previous calculations, the annual number of patients who present with
      massive pulmonary embolism leading to cardiac arrest (and thus who would
      theoretically be candidates for thrombolytic treatment) was estimated to be
      0.7/100000 inhabitants in this emergency medical services system.

PMID- 9783511
TI  - Profound circulatory shock following heroin overdose.
AB  - A 17-year-old previously healthy girl with profound circulatory shock following a
      heroin overdose is reported. Except for opiates no other substances and
      specifically no cocaine were found in the blood and urine samples. Even though
      the mechanism of shock is not completely understood, severe depression of left
      ventricular contractility seems to be the predominant reason. Acute right heart
      failure with decreased pulmonary capillary wedge pressure and arterial
      vasodilatation resulting in maldistribution of cardiac output cannot be ruled out
      as possible contributing factors. The shock was successfully reversed with volume
      loading and a high dose of dobutamine. The recovery was uneventful and the
      patient was discharged with normal cardiac function.

PMID- 9783512
TI  - The Spanish Resuscitation Council: past, present and future.

PMID- 9783513
TI  - Review article on inhalation rewarming.

PMID- 9783514
TI  - External chest compression without undoing the patient's clothes?

PMID- 9783515
TI  - Fluid replacement needs of well-trained male and female athletes during indoor
      and outdoor steady state running.
AB  - Twelve male and six female well-trained middle distance athletes performed a
      series of six one hour runs at 75% VO2 peak pace under similar environmental
      states indoors (treadmill) and outdoors (track). Running was undertaken in
      control (C, no fluid), followed by water (W) and sports drink (SD) treatments,
      with each run separated by a one week interval. Both fluid treatments were
      supplied in volumes equivalent to individual body mass (fluid) losses incurred in
      the respective indoor and outdoor C treatments. Haemodynamic (plasma volume),
      physiological (heart rate and body temperature) and blood chemistry (blood
      lactate and glucose) measures were analysed as pre to post run changes (delta
      values). During the respective indoor and outdoor C treatments, males
      demonstrated approximately a twofold change in body mass (fluid) losses (delta
      1.81 +/- 0.10 kg and 2.06 +/- 0.13 kg) compared with females (delta 0.93 +/- 0.11
      kg and 1.32 +/- 0.12 kg) (all p<0.05). These losses resulted in almost a twofold
      fluid replacement need relative to body mass during the running phases of
      respective indoor and outdoor W and SD treatments in males compared with females
      (all p<0.05). Both W and SD treatments were effective in minimising the pre to
      post run disturbances in plasma volume, heart rate, body temperature and blood
      lactate, while SD treatment resulted in enhanced blood glucose changes. The
      results suggest gender specific differences in fluid replacement needs during
      steady state running, which need to be incorporated into fluid replacement
      strategies to compensate for the demands of training and competition in middle
      distance athletic events.

PMID- 9783516
TI  - The use of a single case design to investigate the effect of a pre-performance
      routine on the water polo penalty shot.
AB  - The pre-performance routine (PPR) is proposed to assist the performance of closed
      skills by enhancing concentration (Crews and Boutcher, 1987) and the recall of
      optimal psychological and physiological states (Cohn, 1990). A multiple-baseline
      across-individuals design was utilised to assess the effect of PPRs on water polo
      penalty shot performance. Three experienced male water polo players were assisted
      in designing a personalised multi-component PPR, which was rehearsed in
      accordance with a training program, and implemented prior to performing penalty
      shots in simulated trials. Mean performance scores increased for all players
      between pre and post intervention phases. A Split Middle analysis (White, 1974)
      further described performance trends and changes. Players 1 and 2 reversed
      negative baseline trends of -1.071 and -1.031 to positive post intervention
      trends of +1.011 and +1.011, producing respective positive changes in slope of
      +1.08 and +1.042. Player 3's baseline trend of +1.008 was reversed post
      intervention to -1.004, causing a negative change in slope of -1.012. Respective
      ratios of 1.38, 1.36 and 1.20, suggest a positive change in trend level
      immediately following PPR introduction. Binomial tests revealed improvements in
      all participant performances between stages (p<0.001). Results are reviewed in
      light of previous research and the utilisation of single-subject designs is
      discussed.

PMID- 9783517
TI  - Altitude training at 2690m does not increase total haemoglobin mass or sea level
      VO2max in world champion track cyclists.
AB  - Haemoglobin mass (Hb mass), maximum oxygen consumption (VO2max), simulated 4000 m
      individual pursuit cycling performance (IP4000), and haematological markers of
      red blood cell (RBC) turnover were measured in 8 male cyclists before and after
      (A) 31 d of altitude training at 2690 m. The dependent variables were measured
      serially after altitude on d A3-4, A8-9 and A20-21. There was no significant
      change in Hb mass over the course of the study and VO2max at d A9 was
      significantly lower than the baseline value (79.3 +/- 0.7 versus 81.4 +/- 0.6 ml
      x kg(-1) x min(-1), respectively). No increase in Hb mass or VO2max was probably
      due to initial values being close to the natural physiological limit with little
      scope for further change. When the IP4000 was analysed as a function of the best
      score on any of the three test days after altitude training there was a 4%
      improvement that was not reflected in a corresponding change in VO2max or Hb
      mass. RBC creatine concentration was significantly reduced after altitude
      training, suggesting a decrease in the average age of the RBC population.
      However, measurement of reticulocyte number and serum concentrations of
      erythropoietin, haptoglobin and bilirubin before and after altitude provided no
      evidence of increased RBC turnover. The data suggest that for these elite
      cyclists any benefit of altitude training was not from changes in VO2max or Hb
      mass, although this does not exclude the possibility of improved anaerobic
      capacity.

PMID- 9783518
TI  - The effect of stage duration on the calculation of peak VO2 during cycle
      ergometry.
AB  - This study investigated the influence of stage duration on the calculation of
      peak oxygen consumption (peak VO2 to determine whether both the lactate threshold
      (LT) and peak VO2 could be measured during the same test without compromising the
      peak VO2 value obtained. Eight moderately-active females (mean age +/- SD = 19.6
      +/- 2.5 years) performed three peak VO2 tests on an electrically-braked cycle
      ergometer. Power output was increased every minute for the short peak VO2 test
      (S) and every three minutes for the long peak VO2 tests (L). Testing took place
      over two weeks with all tests separated by at least 48 hours. The first peak VO2
      test was a long test (L1) and served as familiarisation. The subjects then
      performed a short (S) and a long (L2) peak VO2 test in random, counterbalanced
      order. For each subject, all three tests were performed at the same time of day
      in controlled environmental conditions. There was no significant difference
      between the two exercise protocols for peak VO2 when expressed in ml x kg(-1) x
      min(-1) (F[1,7]=3.47, P=0.105) or in L x min(-1) (F[1,7]=3.39. P=0.108). However,
      the maximum heart rate (HRmax) achieved in S was significantly less than the
      HRmax achieved in L2 (F[1,7]=33.4, P<0.001). The power output at exhaustion
      (Wpeak) was significantly greater in S than in L2 (F[1,7]=56.5, P<0.001). The
      data from this study therefore showed that in moderately-active females, a three
      minute incremental protocol, allowing for the simultaneous calculation of the LT,
      could be used without compromising peak VO2, but that HRmax and Wpeak were
      affected.

PMID- 9783519
TI  - The effect of endurance exercise on muscle force generating capacity of the lower
      limbs.
AB  - The purpose of this study was to investigate the recovery of muscle force
      generating capacity (FGC) of the lower limbs following a session of cycle
      exercise (CE). Fourteen male cyclists (mean +/- SD age 25 +/- 4 yrs and VO2max
      65.8 +/- 5 ml x kg(-1)min(-1)) performed tests assessing lower limb muscle FGC at
      rest (pre-test), as well as 6 and 24 hrs following CE performed on a mechanically
      braked cycle ergometer. The CE consisted of 30 min at a workload corresponding to
      the lactate (Dmax) threshold (+/-15 W), and four 60 s rides at 120% VO2max with
      one min rest between each ride. At the completion of the CE a 6 or 24 hr recovery
      period was initiated, after which, each subject's muscle FGC was measured. The
      analysis of lower limb muscle FGC included, (1) 6 s all-out cycle test; (2) a
      maximal isokinetic leg extension at 60, 120 and 180 degrees x s(-1); and (3) a
      maximal concentric squat jump. Statistical analysis showed that compared to pre
      test levels, a significant reduction in both isokinetic peak torque at 60 degrees
      x s(-1) and isoinertial maximum force occurred after 6 hrs of recovery. Although
      not significant, reductions also occurred at 6 hrs of recovery in isokinetic peak
      torque at 120 and 180 degrees x s(-1), as well as maximum rate of force
      development (RFD) during the squat jumps. No significant differences were
      observed between isokinetic peak torque, maximum force or RFD pre-test and
      following the 24 hr recovery period, indicating these tests had returned to
      normal by this time. No significant differences were found between peak power
      (PP) during the 6 s cycle test, pre-test and following either 6 or 24 hrs of
      recovery. These findings confirm earlier research that maximal voluntary strength
      is reduced for at least 6 hours following exhaustive dynamic exercise. The
      reduction in muscle FGC should be considered when resistance training is
      scheduled after endurance exercise.

PMID- 9783520
TI  - Leap-frogging technology into the next century: better diagnostic tests for TB.

PMID- 9783521
TI  - New tools for the diagnosis of tuberculosis: the perspective of developing
      countries.
AB  - New diagnostics for tuberculosis are urgently needed to replace or facilitate
      acid-fast bacilli (AFB) microscopy for the identification of smear-positive
      cases, and to improve the diagnosis of AFB smear-negative cases. These need to be
      appropriate for use in low income countries. Tests to replace or facilitate AFB
      microscopy must offer improvements to this test, including increased sensitivity,
      speed, ease of use, and safety. Products to improve the identification of smear
      negative cases should focus on the diagnosis of patients with paucibacillary
      pulmonary disease, including children and human immunodeficiency virus (HIV)
      infected persons, and those with extrapulmonary forms of tuberculosis.

PMID- 9783522
TI  - The early history of tuberculosis in central East Africa: insights from the
      clinical records of the first twenty years of Mengo Hospital and review of
      relevant literature.
AB  - SETTING: Mengo Hospital, in present day Kampala, Uganda, 100 years ago.
      OBJECTIVE: To determine the presence of tuberculosis in the Bagandan population
      of central East Africa and elsewhere in Africa at the time of early explorations
      by Europeans. DESIGN: The case records kept by Albert Cook for two decades
      beginning in 1897, 35 years after the first visit of Speke to this region, were
      reviewed for evidence of tuberculosis among Bagandans. Writings of other
      contemporary medical observers were reviewed for evidence of tuberculosis in pre-
      and early-colonial Africa. RESULTS: Well documented cases of tuberculosis were
      observed by Cook beginning in 1897. A minimum total of 93 cases of tuberculosis
      were included in 26 806 admissions to Mengo Hospital from 1897 through 1916. No
      secular trend in the prevalence of tuberculosis among patients admitted was
      apparent. A review of the prior literature concerning tuberculosis in precolonial
      Africa suggests that tuberculosis may have been present in several regions prior
      to European exploration, but was probably absent elsewhere. CONCLUSIONS: The
      concept of all of Africa and all of the people of Africa as virgin soil for
      tuberculosis is rooted in an archaic Eurocentric view of Africa, and cannot be
      supported today by available data.

PMID- 9783523
TI  - Tuberculosis in Africa.

PMID- 9783524
TI  - Tuberculin PPD RT23: still going strong.

PMID- 9783525
TI  - The debate about the stability of PPD RT23 is not closed.

PMID- 9783526
TI  - Childhood tuberculosis in Germany between 1985 and 1994: comparison of three
      selected patient groups.
AB  - SETTING: Clinical and epidemiologic features of childhood tuberculosis in Germany
      are unknown for recent years. The characteristics of patient groups may show
      typical differences, depending on the source of data. OBJECTIVE: To identify
      typical features of childhood tuberculosis in Germany, and to relate the
      characteristics of patient groups to the purpose of the reporting centres.
      DESIGN: Comparative, retrospective, descriptive analysis of clinical and
      notification records by standardized data sheet. Evaluation of cases of active
      tuberculosis in children recorded between 1985 and 1994 at three study centres.
      RESULTS: One clinical study centre was a referral centre for sick children with
      an unclear diagnosis, the second specialized in tuberculosis, and the third was a
      public health office. Almost two thirds (64%) of the 285 evaluated patients were
      four years of age and under. Between 73% and 96% of children suffered from
      pulmonary disease and 17% to 58% were culture positive (range between study
      centres). Source cases had been found for 23% to 52% of children, and the primary
      reason for clinical evaluation was a positive tuberculin test for between 12% and
      57%. Foreign-born children showed characteristic differences. CONCLUSION: The
      characteristics of reported childhood tuberculosis differ depending on the
      reporting centre. A significant number of notified cases were probably wrongly
      diagnosed.

PMID- 9783527
TI  - Knowledge of tuberculosis in high-risk populations: survey of inner city
      minorities.
AB  - SETTING: Educational programs targeted toward individuals at risk for
      tuberculosis are needed. As an initial step in developing future programs, the
      present study was designed to determine the baseline knowledge about tuberculosis
      in at-risk individuals. METHODS: Face-to-face surveys were conducted with 505
      minority subjects in the Kansas City Metropolitan area; health care providers
      were excluded. Thirty-six queries directed toward self-perceived and actual
      tuberculosis knowledge were asked. Data were tabulated and per cent correct
      response was determined. RESULTS: Completed surveys were available from 505
      subjects: 342 females and 163 males. Most (97%) of the subjects were African
      Americans, with 57% between the ages of 21-40. Over two-thirds were high school
      graduates, and 77% reported an estimated total household annual income of
      <$20000. Self-perceived knowledge about tuberculosis was rated as 'little' or
      'nothing' by 60% of respondents. The overall correct response score was 61%, with
      55% correct response to queries related to etiology, 53% for identification of
      high-risk populations, 57% for possible routes of transmission, 89% for symptoms,
      and 49% for treatment. Males, those with annual incomes >$20000, and individuals
      51-70 years old had the highest scores. CONCLUSIONS: In this high-risk inner-city
      population surveyed, knowledge deficits in the etiology, transmission, and
      treatment of tuberculosis were identified.

PMID- 9783528
TI  - Barriers to tuberculosis control in urban Zambia: the economic impact and burden
      on patients prior to diagnosis.
AB  - SETTING: Chest Clinic, University Teaching Hospital, Zambia. OBJECTIVE: To study
      the pre-diagnosis economic impact, burden, and barriers to care-seeking for
      tuberculosis patients in urban Zambia. DESIGN: In-depth interviews conducted over
      a 9-week period with adult in-patients and out-patients registering with new
      pulmonary tuberculosis; data analysis using Epi Info. RESULTS: Interviews were
      completed by 202 patients: 64% normally worked, but 31% stopped due to their
      tuberculosis, with an average of 48 days off. The mean duration of illness prior
      to their tuberculosis registration was 63 days, with 64% of patients delaying in
      presenting to the Chest Clinic. Of these, 38% blamed money shortages for their
      delay. In seeking diagnosis, patients incurred a mean total cost equivalent to
      127% of their mean monthly income (pounds sterling UK 40 [$US 59]); direct
      expenditures represented 60% of this cost. In addition, patients lost, on
      average, 18 work days prior to diagnosis. Care-givers incurred costs equivalent
      to 31% of the mean monthly income (pounds sterling UK 10 [$US 15]). CONCLUSION:
      The economic burden of tuberculosis on patients creates barriers to prompt
      diagnosis which may lead to continuing transmission of the infection. Important
      economic barriers include transportation expenditure, cost of 'special food', and
      lost income. These barriers may be reduced through interventions that reduce the
      number of health encounters, travel distances and duration of illness before
      diagnosis.

PMID- 9783529
TI  - Hypercalcaemia in patients with newly diagnosed tuberculosis in Malaysia.
AB  - SETTING: University Hospital, Kuala Lumpur, Malaysia. OBJECTIVE: To determine the
      incidence of hypercalcaemia in Malaysian patients with newly diagnosed
      tuberculosis (TB) before the commencement of antituberculosis treatment. DESIGN:
      A prospective study of consecutive patients with newly diagnosed
      bacteriologically and/or histologically proven tuberculosis in our institution
      from September 1994 to March 1996. RESULTS: Of a total of 120 patients (67 males,
      53 females), 68 had pulmonary TB, nine had pulmonary and pleural TB, 18 had
      pleural TB without chest radiograph evidence of lung involvement, 16 had various
      other forms of extra-pulmonary TB and nine had disseminated TB. The mean age of
      the patients was 44.3 (+/-18.0) years. The mean albumin-adjusted serum calcium
      concentration was 2.53 (+/-0.22) mmol/l. Hypercalcaemia was present in 27.5% of
      the patients, but only 12% of these patients showed symptoms of hypercalcaemia.
      The type of TB and, in the case of pulmonary TB, the radiographic extent of lung
      involvement, had no effect on the serum calcium level. CONCLUSION: Hypercalcaemia
      is not uncommon among Malaysian patients with newly diagnosed TB, but it is
      rarely symptomatic.

PMID- 9783530
TI  - Bioavailability of rifampicin, isoniazid and pyrazinamide from fixed-dose
      combination capsules.
AB  - SETTING: The absorption of rifampicin, isoniazid and pyrazinamide was tested
      after administration of each drug in free combinations and in a fixed-dose
      combination of the three drugs, known as Trifazid. OBJECTIVE: To examine the
      relative bioavailability of rifampicin, isoniazid and pyrazinamide after oral
      administration of the drugs given alone in comparison to that of the same drugs
      after administration of Trifazid. DESIGN: An open, randomized, cross-over study
      comprising 16 healthy volunteers. RESULTS: The pattern of absorption, plasma
      concentrations and pharmacokinetic parameters were very similar after
      administration of the drugs in free and fixed combinations. CONCLUSION: The
      triple combination of antituberculosis drugs could replace the separate drugs in
      the treatment of tuberculosis.

PMID- 9783531
TI  - Isoenzymes of adenosine deaminase in pleural effusions: a diagnostic tool?
AB  - SETTING: Tygerberg Hospital, an academic teaching hospital, Republic of South
      Africa. OBJECTIVE: To identify the adenosine deaminase (ADA) isoenzymes as a
      diagnostic tool for tuberculosis in pleural effusions with increased ADA
      activity. DESIGN: Patients (n = 157) with exudative effusions and ADA activities
      >20 U/l, due to causes which satisfied predetermined diagnostic criteria,
      participated in the study. They consisted of 87 tuberculous effusions, 27
      infective effusions (12 empyematous and 15 non-empyematous), 37 malignant
      effusions and six other exudative effusions (systemic lupus erythematosus,
      pancreatitis and lung embolus). In each case the ADA isoenzymes in the pleural
      fluid were identified using polyacrylamide gel electrophoresis. In addition,
      microbiology and cytology (including differential cell counts) were also carried
      out. RESULTS: Although ADA1c and ADA2 were the predominant isoenzymes observed in
      tuberculous effusions, while ADA1c and ADA1m were predominant in infective non
      empyematous effusions, no additional diagnostic value was obtained. In the case
      of neoplastic effusions and other exudates, determination of ADA isoenzyme
      patterns also did not assist in diagnosing these conditions. CONCLUSION:
      Determination of patterns of ADA isoenzymes does not enhance the overall
      diagnostic value of ADA activity in pleural effusions.

PMID- 9783532
TI  - The cytokine response to bacille Calmette Guerin vaccination in South India.
AB  - SETTING: Evaluation of immune response after BCG vaccination in a population from
      South India where BCG vaccination was a failure. OBJECTIVE: To study the cell
      mediated immune responses (CMI) in vitro by assessing skin test conversion,
      lymphocyte proliferation and cytokine patterns before and after BCG vaccination
      in 20 Mantoux negative subjects, and to compare this with that of 20 naturally
      Mantoux positive subjects. DESIGN: In vitro lymphocyte proliferation and cytokine
      responses to various mycobacterial antigens were studied in 12 subjects from each
      group. The cytokines interferon gamma (IFN-gamma), interleukin (IL)-4 and IL-10
      were measured by both reverse transcriptase polymerase chain reaction (RT-PCR)
      and enzyme linked immunosorbent assay (ELISA). RESULTS: All of those who were
      initially Mantoux negative but one subject converted to positivity following
      vaccination, confirming that BCG vaccination does cause skin test conversion.
      However, in vitro proliferative responses to phytohaemagglutinin (PHA), purified
      protein derivative (PPD) and Mycobacterium tuberculosis remained largely
      unaltered by vaccination. The production of IFN-gamma was significantly higher in
      PPD-positive individuals compared to the PPD-negative group, and BCG vaccination
      of the latter did not change the levels of IFN-gamma, IL-4 or IL-10. CONCLUSIONS:
      The finding that PPD-negative individuals did not produce IFN-gamma even
      following vaccination and skin test conversion suggests that BCG had little
      effect in driving the immune response towards a protective Th1 type.

PMID- 9783533
TI  - Childhood human immunodeficiency virus and tuberculosis co-infections:
      reconciling conflicting data.
AB  - The impact of the human immunodeficiency virus (HIV) pandemic on childhood
      tuberculosis (TB) is unclear because of inconsistent and often contradictory
      findings in different types of studies. We review the evidence which supports or
      refutes the likelihood that HIV infection in children predisposes them to TB, and
      conclude that, on balance, HIV during infancy increases the risk of developing
      TB. Surveillance shows an association between rising TB rates among children and
      the HIV epidemic in some parts of the world. A number of cross-sectional studies
      which have taken children with TB as their starting population, have yielded high
      rates of association with HIV (11%-64% HIV prevalence). Similarly, cross
      sectional studies of hospitalised children with HIV show that many also have TB.
      These rates of association are all over-estimated because of the uncertainty of
      diagnosis of TB. Birth cohorts of perinatally HIV-infected infants and children
      prospectively followed up for a few years have generally failed to detect a
      higher incidence of TB than anticipated. The few TB cases identified in these
      cohorts were usually over 15-18 months of age. In acute progressive lung disease
      there is no excess of TB in HIV-infected over non HIV-infected children. These
      inconsistencies are discussed and attributed mainly to study design and
      statistical artefact. However, maternal factors in HIV-positive women which might
      affect transmission of TB to their babies are assessed, and infant immunoparesis
      due to HIV which may adversely influence resistance to TB is considered.

PMID- 9783534
TI  - Information management in national tuberculosis control programmes and national
      health information systems.
AB  - A good notification system is one of the key elements for the success of national
      tuberculosis programmes (NTPs). The national health information system (NHIS) in
      low income countries is often weak and unreliable. When restructuring this
      system, what circuit should be used to integrate TB data: the NTP or the NHIS?
      Experience from several countries shows that unlike the NHIS, only the data
      generated by the NTP are reliable and complete, and arrive rapidly enough to be
      used for programme management. It is therefore the duty of the NTP to collect
      this information and transmit it to the NHIS at each level of the health system.
      These were the conclusions of a seminar held in Cotonou, Benin, organised by the
      International Union Against Tuberculosis and Lung Disease, which involved the
      leaders of the NHIS and of NTPs of six West African countries.

PMID- 9783535
TI  - Tuberculin PPD RT23: has it lost some of its potency?
AB  - PPD RT23 is a tuberculin that is used worldwide. Korea has been using 1TU RT23
      for its nationwide tuberculosis prevalence surveys at five-yearly intervals since
      1965, and found a drop in its potency after the 1975 survey. This finding draws
      attention to the interpretation of tuberculin survey data observed with RT23 at
      different time periods.

PMID- 9783536
TI  - Clarithromycin for non-mycobacterial diseases?

PMID- 9783537
TI  - Sputum microscopy at 2 and 3 months.

PMID- 9783538
TI  - The origins of DOT.

PMID- 9783539
TI  - The enkephalinergic osteoblast.

PMID- 9783540
TI  - A BMP responsive transcriptional region in the chicken type X collagen gene.
AB  - Bone morphogenetic proteins (BMPs) were originally identified by their ability to
      induce ectopic bone formation and have been shown to promote both chondrogenesis
      and chondrocyte hypertrophy. BMPs have recently been found to activate a membrane
      serine/threonine kinase signaling mechanism in a variety of cell types, but the
      downstream effectors of BMP signaling in chondrocyte differentiation remain
      unidentified. We have previously reported that BMP-2 markedly stimulates type X
      collagen expression in prehypertrophic chick sternal chondrocytes, and that type
      X collagen mRNA levels in chondrocytes cultured under serum-free (SF) conditions
      are elevated 3- to 5-fold within 24 h. To better define the molecular mechanisms
      of induction of chondrocyte hypertrophy by BMPs, we examined the effect of BMPs
      on type X collagen production by 15-day chick embryo sternal chondrocytes
      cultured under SF conditions in the presence or absence of 30 ng/ml BMP-2, BMP-4,
      or BMP-7. Two populations of chondrocytes were used: one representing resting
      cartilage isolated from the caudal third of the sterna and the second
      representing prehypertrophic cartilage from the cephalic third of the sterna. BMP
      2, BMP-4, and BMP-7 all effectively promoted chondrocyte maturation of cephalic
      sternal chondrocytes as measured by high levels of alkaline phosphatase,
      diminished levels of type II collagen, and induction of the hypertrophic
      chondrocyte-specific marker, type X collagen. To test whether BMP control of type
      X collagen expression occurs at the transcriptional level, we utilized plasmid
      constructs containing the chicken collagen X promoter and 5' flanking regions
      fused to a reporter gene. Constructs were transiently transfected into sternal
      chondrocytes cultured under SF conditions in the presence or absence of 30 ng/ml
      BMP-2, BMP-4, or BMP-7. A 533 bp region located 2.4-2.9 kb upstream from the type
      X collagen transcriptional start site was both necessary and sufficient for
      strong BMP responsiveness in cells destined for hypertrophy, but not in
      chondrocytes derived from the lower sterna.

PMID- 9783541
TI  - Mouse osteoblastic cell line (MC3T3-E1) expresses extracellular calcium (Ca2+o)
      sensing receptor and its agonists stimulate chemotaxis and proliferation of MC3T3
      E1 cells.
AB  - The calcium-sensing receptor (CaR) is a G protein-coupled receptor that plays key
      roles in extracellular calcium ion (Ca2+o) homeostasis in parathyroid gland and
      kidney. Osteoblasts appear at sites of osteoclastic bone resorption during bone
      remodeling in the "reversal" phase following osteoclastic resorption and
      preceding bone formation. Bone resorption produces substantial local increases in
      Ca2+o that could provide a signal for osteoblasts in the vicinity, leading us to
      determine whether such osteoblasts express the CaR. In this study, we used the
      mouse osteoblastic, clonal cell line MC3T3-E1. Both immunocytochemistry and
      Western blot analysis, using an antiserum specific for the CaR, detected CaR
      protein in MC3T3-E1 cells. We also identified CaR transcripts in MC3T3-E1 cells
      by Northern analysis using a CaR-specific riboprobe and by reverse transcription
      polymerase chain reaction with CaR-specific primers, followed by nucleotide
      sequencing of the amplified products. Exposure of MC3T3-E1 cells to high Ca2+o
      (up to 4.8 mM) or the polycationic CaR agonists, neomycin and gadolinium (Gd3+),
      stimulated both chemotaxis and DNA synthesis in MC3T3-E1 cells. Therefore, taken
      together, our data strongly suggest that the osteoblastic cell line MC3T3-E1
      possesses both CaR protein and mRNA very similar, if not identical, to those in
      parathyroid and kidney. Furthermore, the CaR in these osteoblasts could play a
      key role in regulating bone turnover by stimulating the proliferation and
      migration of such cells to sites of bone resorption as a result of local release
      of Ca2+o.

PMID- 9783542
TI  - 17Beta-hydroxysteroid dehydrogenases in human bone cells.
AB  - Interconversion of estrogens by osteoblasts may play a role in regulating bone
      mass. As a first step toward exploring this possibility, we investigated the
      expression and activity of 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) in
      cultured human osteoblasts (HOB) and osteoblast-like osteosarcoma cells (MG63,
      TE85, and SaOS-2). Significant 17beta-HSD activity was detected in cell-free
      extracts of all bone cells with oxidation of estradiol to estrone predominating
      over reduction. Reverse transcription-polymerase chain reaction (RT-PCR)
      experiments showed that the mRNA for 17beta-HSD I was detectable only in MG63
      cells, albeit at low levels, while 17beta-HSD II was present in MG63, TE85, and
      HOB, but not SaOS-2, and 17beta-HSD III was absent from each bone cell type.
      17Beta-HSD IV was the only isoform present in all bone cells analyzed. Further
      analysis of the expression of 17beta-HSD IV in these bone cells by immunoblotting
      revealed both the full-length 83 kDa protein and the proteolytic 38 kDa form. The
      kinetic parameters for estradiol oxidation by purified recombinant 17beta-HSD IV
      (Km = 49.7 microM, Vmax = 79.4 nmol/minute/mg of protein) and its HSD-domain (Km
      = 79.4 microM, Vmax = 476 nmol/minute/mg of protein) were significantly higher
      than previously reported, but consistent with the values obtained with crude cell
      free extracts of SaOS-2 cells (Km = 98.8 microM, Vmax = 0.07 nmol/minute/mg of
      protein) which contain only 17beta-HSD IV based on RT-PCR. These studies show
      that bone cells have the capacity to interconvert circulating estrogens and
      suggest that bone cell 17beta-HSDs serve primarily to attenuate the continuing
      actions of estradiol through conversion to its less potent form, estrone, under
      certain conditions.

PMID- 9783543
TI  - Normal human cementum-derived cells: isolation, clonal expansion, and in vitro
      and in vivo characterization.
AB  - Cultures of primary human cementum-derived cells (HCDCs) were established from
      healthy premolar teeth extracted for orthodontic reasons. Cementum was manually
      dissected, fragmented, and digested twice with collagenase. Following a thorough
      wash to remove liberated cells, the remaining cementum fragments were plated in
      Dulbecco's modified Eagle's medium/F12 medium containing 10% fetal bovine serum.
      Discrete colonies that contained cells exhibiting fibroblast-like morphology were
      visible after 14-21 days of culture. When the colonies became sufficiently large,
      cells from individual colonies were isolated and subcultured. Cementum-derived
      cells exhibited low levels or no alkaline phosphatase activity and mineralized in
      vitro to a lesser degree than human periodontal ligament (PDL) cells and human
      bone marrow stromal cell (BMSC) cultures. To study differentiation capacities of
      HCDCs, cells were attached to hydroxyapatite/tricalcium phosphate ceramic and
      transplanted subcutaneously into immunodeficient mice. The transplants were
      harvested 3, 6, and 8 weeks after transplantation and evaluated histologically.
      In human BMSC transplants, new bone tissue was formed with a prominent
      osteoblastic layer and osteocytes embedded in mineralized bone matrix. No osseous
      tissue was formed by PDL cells. Of six single colony-derived strains of HCDCs
      tested, three formed a bone-like tissue that featured osteocyte/cementocyte-like
      cells embedded within a mineralized matrix and which was lined with a layer of
      cells, although they were somewhat more elongated than osteoblasts. These results
      show that cells from normal human cementum can be isolated and expanded in vitro.
      Furthermore, these cells are capable of differentiating and forming mineralized
      tissue when transplanted into immunodeficient mice.

PMID- 9783544
TI  - Osteocyte shape is dependent on actin filaments and osteocyte processes are
      unique actin-rich projections.
AB  - Osteocytes are derived from a select group of osteoblasts that have undergone a
      final differentiation. Due to their inaccessibility when embedded in the bone
      matrix, very little is known about the osteocyte cytoskeleton. This study
      provides an extensive analysis of the osteocyte cytoskeleton, based on the
      successful isolation of osteocytes from 16-day embryonic chick calvariae. We used
      OB7.3, a chicken osteocyte-specific monoclonal antibody, to confirm the
      osteocytic phenotype of the isolated cells and established culture conditions to
      promote growth of cells that most resemble osteocytes in vivo. Immunofluorescence
      staining with antitubulin, antivimentin, and antiactin showed the relative
      distribution of the microtubules, intermediate filaments, and actin filaments in
      both osteocyte cell body and processes. Field emission scanning electron
      microscopy revealed the three-dimensional relationships of the cytoskeletal
      elements and a unique organization of actin bundles that spanned the cell body
      and osteocyte processes. When combined with drug studies, these experiments
      demonstrate that actin filaments are crucial for the maintenance of osteocyte
      shape. Furthermore, we identified two actin-bundling proteins, alpha-actinin and
      fimbrin, in osteocyte processes. The prominence and unique distribution of
      fimbrin in osteocyte processes provides the possibility of its use as an
      intracellular marker to distinguish osteocytes from osteoblasts.

PMID- 9783545
TI  - Association of a polymorphism of the transforming growth factor-beta1 gene with
      genetic susceptibility to osteoporosis in postmenopausal Japanese women.
AB  - Transforming growth factor-beta (TGF-beta) is both abundant in bone and an
      important regulator of bone metabolism. A T-->C transition at nucleotide 29 in
      the signal sequence region of the TGF-beta1 gene results in a Leu-->Pro
      substitution at amino acid position 10. The possible association of this
      polymorphism with bone mass and the prevalence of osteoporosis has now been
      investigated in a total of 287 postmenopausal women from two regions (Obu City,
      Aichi Prefecture, and Sanda City, Hyogo Prefecture) of Japan. A significant
      association of TGF-beta1 genotype with bone mass was detected in both
      populations; bone mineral density (BMD) at the lumbar spine was greater in
      individuals with the CC genotype than in those with the TT or TC genotype. The
      frequency of vertebral fractures was significantly lower in individuals with the
      CC genotype than in those with the TC or TT genotypes. For each region,
      multivariable logistic regression analysis revealed that the frequency of the T
      allele was significantly higher in subjects with osteoporosis than in controls.
      Also, the serum concentration of TGF-beta1 in individuals with the CC genotype
      was significantly higher than that in age-matched subjects with the TC or TT
      genotype in osteoporotic or osteopenic as well as healthy control groups. These
      results suggest that the T/C polymorphism of the TGF-beta1 gene is one of the
      genetic determinants of bone mass and that the T allele is an independent risk
      factor for the genetic susceptibility to osteoporosis in postmenopausal Japanese
      women. Thus, analysis of the TGF-beta1 genotype may be useful in the prevention
      and management of osteoporosis.

PMID- 9783546
TI  - Effects of estrogen therapy of postmenopausal women on cytokines measured in
      peripheral blood.
AB  - Estrogen replacement therapy (ERT) is known to prevent bone loss following the
      menopause, but the mechanism for this is unclear. Estrogen may suppress the
      secretion of certain bone-resorbing cytokines. The aim of this study was to
      assess the effect of ERT on the levels of cytokines measured in peripheral blood.
      We measured cytokines in 10 postmenopausal women (ages 56-59, 3-9 years since
      menopause) treated with ERT and 10 age-matched (54-59 years, 4-10 years since
      menopause) untreated women as controls. Samples of blood were taken and used for
      mononuclear cell cultures, whole blood (WB) cultures, and the separation of
      serum. The cultures were treated with lipopolysaccharide (LPS; 500 ng/ml) and
      hydrocortisone (10(-6) M). The conditioned medium from cultures and the serum
      were then assayed for interleukin-6 (IL-6), IL-1alpha IL-1beta, IL-1 IL-1ra,
      tumor necrosis factor alpha (TNF-alpha), and granulocyte macrophage colony
      stimulating factor (GM-CSF) by enzyme-linked immunosorbent assay. M-CSF and the
      soluble cytokine receptors soluble IL-6 receptor (sIL-6r) and soluble TNF
      receptor type 1 (sTNFr1) were also measured in serum and M-CSF in stimulated WB
      cultures. Measurements were corrected for mononuclear cell count. We also
      measured serum bone-specific alkaline phosphatase (ibAP) in all subjects. We
      found that LPS stimulated secretion of all cytokines both in WB and isolated cell
      cultures, and that this was attenuated by hydrocortisone. A significantly higher
      ratio of IL-1beta/IL-1ra (p = 0.02) in LPS stimulated WB cultures was seen in the
      untreated women. Levels of IL-1beta and IL-1alpha measured in WB cultures were
      lower and IL-1ra was higher in the ERT-treated group but these results were not
      significant. BAP was higher in the untreated group (p = 0.005) and correlated
      with IL-alpha/IL-1ra in the whole group (r = 0.49, p = 0.03). Results of other
      measurements showed no significant differences between groups. We conclude that
      estrogen may prevent bone loss following the menopause by altering the balance
      between IL-1beta and IL-1ra.

PMID- 9783547
TI  - Hip fracture prediction in elderly men and women: validation in the Rotterdam
      study.
AB  - The aim of our study was to validate a hip fracture risk function, composed of
      age and femoral neck bone mineral density (BMD). This estimate of the 1-year
      cumulative risk was previously developed on the basis of Dutch hip fracture
      incidence data and BMD in men and women. A cohort of 7046 persons (2778 men) aged
      55 years and over was followed for an average of 3.8 years. The 1-year hip
      fracture risk estimate was calculated for each participant according to the risk
      function and categorized as low (<0.1%), moderate (0.1 to < 1%), or high (> or
      =1%). Observed first hip fracture incidence was then analyzed for each of these
      risk categories by age and gender. Additionally, we calculated the relative risk
      per standard deviation (SD) decrease in femoral neck BMD in this population. At
      baseline, 2360 individuals were categorized as low risk, 2567 as moderate risk,
      and 378 as high risk During follow-up, 110 first hip fractures were observed
      corresponding to an incidence rate of 4.1/1000 person-years (pyrs) (95%
      confidence interval 3.4-5.0). The observed incidence rate in the low risk group
      was 0.2/1000 pyrs (0.1-0.9), 2.7/1000 pyrs (1.8-3.9) in the moderate risk group,
      and 18.4/1000 pyrs (12.4-27.2) in the high risk group. Below the age of 70 years,
      incidence was low in all categories, and very few individuals were considered at
      high risk Above the age of 70 years, the observed incidence was high in the high
      risk group, while in the low and moderate risk groups, the incidence remained low
      even over 80 years of age. In women, the age-adjusted relative risk for hip
      fractures was 2.5 per SD decrease in femoral neck BMD (1.8-3.6), while in men
      this relative risk was 3.0 per SD (1.7-5.4). In conclusion, we observed a similar
      relation of hip fracture with femoral neck BMD in men and women and were able to
      predict accurately hip fracture rates over a period of almost 4 years.

PMID- 9783548
TI  - The effects of twelve weeks of bed rest on bone histology, biochemical markers of
      bone turnover, and calcium homeostasis in eleven normal subjects.
AB  - This study was undertaken to examine the effects of 12 weeks of skeletal
      unloading on parameters of calcium homeostasis, calcitropic hormones, bone
      histology, and biochemical markers of bone turnover in 11 normal subjects (9 men,
      2 women; 34 +/- 11 years of age). Following an ambulatory control evaluation, all
      subjects underwent 12 weeks of bed rest. An additional metabolic evaluation was
      performed after 12 days of reambulation. Bone mineral density declined at the
      spine (-2.9%, p = 0.092) and at the hip (-3.8%, p = 0.002 for the trochanter).
      Bed rest prompted a rapid, sustained, significant increase in urinary calcium and
      phosphorus as well as a significant increase in serum calcium. Urinary calcium
      increased from a pre-bed rest value of 5.3 mmol/day to values as high as 73
      mmol/day during bed rest. Immunoreactive parathyroid hormone and serum 1,25
      dihydroxyvitamin D declined significantly during bed rest, although the mean
      values remained within normal limits. Significant changes in bone histology
      included a suppression of osteoblastic surface for cancellous bone (3.1 +/- 1.3%
      to 1.9 +/- 1.5%, p = 0.0142) and increased bone resorption for both cancellous
      and cortical bone. Cortical eroded surface increased from 3.5 +/- 1.1% to 7.3 +/-
      4.0% (p = 0.018) as did active osteoclastic surface (0.2 +/- 0.3% to 0.7 +/-
      0.7%, p = 0.021). Cancellous eroded surface increased from 2.1 +/- 1.1% to 4.7 +/
      2.2% (p = 0.002), while mean active osteoclastic surface doubled (0.2 +/- 0.2%
      to 0.4 +/- 0.3%, p = 0.020). Serum biochemical markers of bone formation
      (osteocalcin, bone-specific alkaline phosphatase, and type I procollagen
      extension peptide) did not change significantly during bed rest. Urinary
      biochemical markers of bone resorption (hydroxyproline, deoxypyridinoline, and N
      telopeptide of type I collagen) as well as a serum marker of bone resorption
      (type I collagen carboxytelopeptide) all demonstrated significant increases
      during bed rest which declined toward normal during reambulation. Thus, under the
      conditions of this study, the human skeleton appears to respond to unloading by a
      rapid and sustained increase in bone resorption and a more subtle decrease in
      bone formation.

PMID- 9783549
TI  - A longitudinal study of bone gain in pubertal girls: anthropometric and
      biochemical correlates.
AB  - The aim of this longitudinal study was to investigate the factors associated with
      bone mineral acquisition in pubertal girls. Subjects were 37 healthy, Caucasian
      girls aged 12.1 years (SD 0.3). Measurements were made at 6-month intervals over
      a period of 18 months and included total body bone mineral content (TBBMC), total
      body bone mineral density (TBBMD), lean mass, and fat mass by dual-energy X-ray
      absorptiometry, anthropometry, lifestyle factors, four biochemical markers of
      bone turnover, hormonal status, and fractional calcium absorption. In multiple
      regression analysis, correlates of relative gain in TBBMC were gain in lean mass
      (p < 0.001) and estradiol (p = 0.008). For TBBMD, correlates were gain in lean (p
      < 0.001) and fat mass (p = 0.003), estradiol (p < 0.001), dietary energy intake
      (p = 0.003), and parathyroid hormone (p = 0.023). Statural growth and gain in
      bone mass were unrelated; both height velocity and bone turnover peaked
      approximately 20 months prior to menarche, whereas gain in bone mass peaked at
      menarche. Bone turnover markers correlated with height velocity (0.40 < r <
      0.62), but not with bone gain. Estradiol was independently and negatively
      associated with all markers of bone turnover (-0.67 < r < -0.80). We conclude
      that estradiol is an important determinant of bone mineral gain in pubertal girls
      and is probably responsible for the reduction in bone turnover in late puberty;
      lean mass was the body composition parameter most closely associated with bone
      gain; height gain and bone gain are dissociated during the period of rapid growth
      at puberty; and bone turnover markers are modestly related to height gain, but
      are not predictive of bone gain.

PMID- 9783550
TI  - Bone mineral and body composition measurements: cross-calibration of pencil-beam
      and fan-beam dual-energy X-ray absorptiometers.
AB  - Pencil-beam dual-energy X-ray absorptiometers (DXA) are being replaced with
      instruments that rely solely on fan-beam technology. However, information has
      been lacking regarding the translation of bone mineral and body composition data
      between the two devices. We have compared total body scans using pencil-beam
      (Hologic QDR-2000W) and fan-beam (Hologic QDR-4500A) instruments for 33 children
      (ages 3-18 years) and 14 adults. Bone mineral content (BMC), bone mineral density
      (BMD), fat, lean, and body fatness (%fat) values were highly correlated (r2 =
      0.984-0.998) between the two DXA instruments. The mean differences between the
      paired measurements were: deltaBMC = 7.5 +/- 73.6 g, deltaBMD = 0.0074 +/- 0.0252
      g/cm2, delta lean = 1.05 +/- 1.8 kg, delta fat = -0.77 +/- 1.7 kg, and delta%fat
      = -0.94% +/- 2.5%. The BMC and BMD values were not statistically different,
      whereas the differences for the body composition values were significant (p <
      0.02-0.005). Regression equations are provided for conversion of bone and body
      composition data between pencil-beam and fan-beam values for the whole body. To
      test the performance of these equations for a second group (23 subjects),
      predicted values were compared with the measured data obtained using the fan-beam
      instrument. The mean differences were -1.0% to 1.4%, except for body fat mass,
      where the difference was 6.4%. For cross-sectional studies, the two DXA
      technologies can be considered equivalent after using the translational equations
      provided. For longitudinal studies in which small changes in body composition for
      the individual are to be detected, we recommend that the same DXA instrument be
      used whenever possible. For example, transition from a pencil-beam to a fan-beam
      instrument could, in extreme cases, result in differences as large as 19% for the
      estimate of body fat mass.

PMID- 9783551
TI  - Leukemia inhibitory factor and oncostatin M influence the mineral phases formed
      in a murine heterotopic calcification model: a Fourier transform-infrared
      microspectroscopic study.
AB  - The study of bone mineralization processes is of considerable interest in
      understanding bone diseases and developing new therapies for skeletal disorders,
      particularly since bone homeostasis requires numerous cell types and a large
      cytokine network. Cell culture models of mineralization have often been used to
      study the cellular mechanisms of mineralization, but few data have been reported
      concerning the influence of extracellular matrix components and cytokines on the
      physicochemical properties of mineral. The purpose of this study was to analyze
      the effects of two cytokines, leukemia inhibitory factor (LIF) and oncostatin M
      (OSM), involved in bone metabolism on the physicochemical properties of bone
      mineral formed in a murine in vivo mineralization model. Murine bone marrow cells
      implanted under the kidney capsule in the presence or absence of cytokines led to
      heterotopic ossicle formation. A scanning electron microscopic microprobe
      revealed that heterotopic calcification had a lower (approximately 20%) Ca/P
      ratio after cytokine treatment as compared with the control without cytokine.
      Transmission electron microscopic analysis of cytokine-treated ossicles showed
      numerous areas with low mineral density, whereas electron diffraction pattern
      revealed an apatitic phase. These areas were not observed in the absence of
      cytokine. Moreover, Fourier transform-infrared microspectroscopy showed at the
      molecular level that the presence of either cytokine induced many microscopic
      areas in which short-range order organization, such as incorporation of carbonate
      and crystallinity/maturity of ossicle mineral, were modified. LIF and OSM
      influenced mineral phase formation in the present model and may thus be key
      protagonists in bone mineral development and skeletal diseases.

PMID- 9783552
TI  - A novel polymorphism in the promoter region for the human osteocalcin gene: the
      possibility of a correlation with bone mineral density in postmenopausal Japanese
      women.
AB  - We present a polymorphism of the human osteocalcin gene (also known as BGP, for
      bone Gla protein) due to a 1 base pair (bp) substitution from cytosine to thymine
      at position 298 nucleotides (nt), which is at position 198 nt upstream from the
      BGP exon 1. This mutation was detected by single-strand conformation polymorphism
      analysis after polymerase chain reaction for the osteocalcin gene fragment (326
      bp) and sequencing analysis. The cytosine/thymine polymorphism can be defined by
      restriction fragment length polymorphism analysis using a modified primer pair
      and the restriction endonuclease HindIII. The osteocalcin genotype was determined
      in 160 postmenopausal Japanese women (age 48-80 years). Osteocalcin alleles were
      designated according to the absence (H) or presence (h) of the HindIII
      restriction site. There were 12 HH, 49 Hh, and 99 hh individuals, and the allele
      frequencies were 22.8% for H and 77.2% for h. To determine if genetic variation
      influences bone mineral density (BMD) and thus can be a determinant of
      susceptibility to osteoporosis in older women, we examined the association of BMD
      with the osteocalcin genotypes found in the present study. The subjects with
      genotype HH had the smallest BMD and those with hh had the greatest BMD among
      subjects, but these differences did not reach statistical significance. The
      HindIII genotype showed a significant effect on the prevalence of osteopenia in
      the subjects, that is, women with genotype HH had a 5.74 times greater risk for
      osteopenia (p < 0.05) and those with genotype Hh had a 1.59 times greater risk
      than women with genotype hh. We identified the osteocalcin gene polymorphism,
      detected with the HindIII genotype, which was suggested to influence bone density
      and is a possible genetic marker for bone metabolism.

PMID- 9783553
TI  - Parathyroid hormone-related protein mRNA and protein expression in multiple
      myeloma: a case report.
AB  - Multiple myeloma frequently leads to complications, such as osteolytic lesions,
      hypercalcemia, and pathological fractures. Increased bone resorption in myeloma
      is due to osteoclast activation. The nature of the osteoclast activator(s)
      remains unclear. We describe a case of multiple myeloma with marked hypercalcemia
      and skeletal complications that progressed rapidly despite chemotherapy. The
      patient had marked hypercalcemia at diagnosis (4.5 mmol/l), and elevated
      parathyroid hormone-related protein (PTHrP) levels were found in plasma. Analysis
      of the bone marrow trephine biopsy showed PTHrP gene transcription and protein in
      myeloma cells. These results provide strong evidence for the production of
      significant amounts of PTHrP by human myeloma cells. PTHrP has been measured as
      elevated in the plasma of patients with myeloma and might be an important
      contributor to the skeletal complications in this disease.

PMID- 9783554
TI  - Beginning to see the light.

PMID- 9783555
TI  - A turning point for seasonal affective disorder and light therapy research?

PMID- 9783556
TI  - Four out of five ain't bad.

PMID- 9783557
TI  - A controlled trial of timed bright light and negative air ionization for
      treatment of winter depression.
AB  - BACKGROUND: Artificial bright light presents a promising nonpharmacological
      treatment for seasonal affective disorder. Past studies, however, have lacked
      adequate placebo controls or sufficient power to detect group differences. The
      importance of time of day of treatment--specifically, morning light superiority-
      has remained controversial. METHODS: This study used a morning x evening light
      crossover design balanced by parallel-group controls, in addition to a nonphotic
      control, negative air ionization. Subjects with seasonal affective disorder (N =
      158) were randomly assigned to 6 groups for 2 consecutive treatment periods, each
      10 to 14 days. Light treatment sequences were morning-evening, evening-morning,
      morning-morning, and evening-evening (10,000 lux, 30 min/d). Ion density was 2.7
      x 10(6) (high) or 1.0 x 10(4) (low) ions per cubic centimeter (high-high and low
      low sequences, 30 min/d in the morning). RESULTS: Analysis of depression scale
      percentage change scores showed low-density ion response to be inferior to all
      other groups, with no other group differences. Response to evening light was
      reduced when preceded by treatment with morning light, the sole sequence effect.
      Stringent remission criteria, however, showed significantly higher response to
      morning than evening light, regardless of treatment sequence. CONCLUSIONS: Bright
      light and high-density negative air ionization both appear to act as specific
      antidepressants in patients with seasonal affective disorder. Whether clinical
      improvement would be further enhanced by their use in combination, or as
      adjuvants to medication, awaits investigation.

PMID- 9783558
TI  - Bright light treatment of winter depression: a placebo-controlled trial.
AB  - BACKGROUND: Bright light therapy is the recommended treatment for winter seasonal
      affective disorder (SAD). However, the studies with the best placebo controls
      have not been able to demonstrate that light treatment has a benefit beyond its
      placebo effect. METHODS: Ninety-six patients with SAD completed the study.
      Patients were randomly assigned to 1 of 3 treatments for 4 weeks, each 1.5 hours
      per day: morning light (average start time about 6 AM), evening light (average
      start about 9 PM), or morning placebo (average start about 6 AM). The bright
      light (approximately 6000 lux) was produced by light boxes, and the placebos were
      sham negative-ion generators. Depression ratings using the Structured Interview
      Guide for the Hamilton Depression Rating Scale, SAD version (SIGH-SAD) were
      performed weekly. RESULTS: There were no differences among the 3 groups in
      expectation ratings or mean depression scores after 4 weeks of treatment.
      However, strict response criteria revealed statistically significant differences;
      after 3 weeks of treatment morning light produced more of the complete or almost
      complete remissions than placebo. By 1 criterion (24-item SIGH-SAD score <50% of
      baseline and < or =8), 61% of the patients responded to morning light, 50% to
      evening light, and 32% to placebo after 4 weeks of treatment. CONCLUSIONS: Bright
      light therapy had a specific antidepressant effect beyond its placebo effect, but
      it took at least 3 weeks for a significant effect to develop. The benefit of
      light over placebo was in producing more of the full remissions.

PMID- 9783560
TI  - Serotonin 1A receptors, melatonin, and the proportional control thermostat in
      patients with winter depression.
AB  - BACKGROUND: In patients with seasonal affective disorder, light treatment lowers
      core temperature during sleep in proportion to its antidepressant efficacy. The
      regulation of the level of core temperature during sleep is linked with a
      proportional control thermostat in the central nervous system whose operation
      appears abnormal in patients with seasonal affective disorder. Because both
      melatonin and serotonin 1A receptor activation also lower core temperature, we
      investigated the relationship between (1) endogenous melatonin and core
      temperature profiles, (2) the proportional control thermostat, and (3) the core
      hypothermic response to the serotonin 1A receptor partial agonist ipsapirone
      hydrochloride in patients with seasonal affective disorder and healthy controls.
      METHODS: Eighteen patients with seasonal affective disorder and 18 controls first
      completed a 24-hour study in which their melatonin profiles were characterized.
      Subjects then returned 3 to 5 days later for the first of 2 drug challenges
      (ipsapirone hydrochloride, 0.3 mg/kg, or placebo), each separated by 3 to 5 days.
      Overnight rectal and facial temperatures were recorded before and after each drug
      challenge. RESULTS: The magnitudes of the core hypothermic responses to
      ipsapirone were (1) not different between groups and (2) independently correlated
      with both the levels of the previous nights' core temperature minima (P=.002) and
      the amounts of nocturnal melatonin secreted (P<.001). CONCLUSION: The daytime
      regulation of core temperature by serotonin 1A receptors appears normal in
      seasonal affective disorder. The magnitude of serotonin 1A receptor-activated
      hypothermia is governed by a central nervous system proportional control
      thermostat whose operation appears modulated by both melatonin and the level of
      the core temperature minimum.

PMID- 9783559
TI  - Morning vs evening light treatment of patients with winter depression.
AB  - BACKGROUND: According to the phase-shift hypothesis for winter depression,
      morning light (which causes a circadian phase advance) should be more
      antidepressant than evening light (which causes a delay). Although no studies
      have shown evening light to be more antidepressant than morning light,
      investigations have shown either no difference or morning light to be superior.
      The present study assesses these light-exposure schedules in both crossover and
      parallel-group comparisons. METHODS: Fifty-one patients and 49 matched controls
      were studied for 6 weeks. After a prebaseline assessment and a light/dark and
      sleep/wake adaptation baseline week, subjects were exposed to bright light at
      either 6 to 8 AM or 7 to 9 PM for 2 weeks. After a week of withdrawal from light
      treatment, they were crossed over to the other light schedule. Dim-light
      melatonin onsets were obtained 7 times during the study to assess circadian phase
      position. RESULTS: Morning light phase-advanced the dim-light melatonin onset and
      was more antidepressant than evening light, which phase-delayed it. These
      findings were statistically significant for both crossover and parallel-group
      comparisons. Dim-light melatonin onsets were generally delayed in the patients
      compared with the controls. CONCLUSIONS: These results should help establish the
      importance of circadian (morning or evening) time of light exposure in the
      treatment of winter depression. We recommend that bright-light exposure be
      scheduled immediately on awakening in the treatment of most patients with
      seasonal affective disorder.

PMID- 9783561
TI  - A controlled study of cortical gray matter and ventricular changes in alcoholic
      men over a 5-year interval.
AB  - BACKGROUND: We report on structural brain changes during a 5-year period in
      healthy control and alcoholic men. METHODS: Alcoholic patients (n = 16), from an
      initial group of 58 who underwent brain magnetic resonance imaging scanning while
      in treatment, were rescanned with the same acquisition sequence approximately 5
      years later. Control subjects (n = 28) spanning the same age range also were
      scanned twice at a comparable interval. Changes in brain volume were corrected
      for error due to differences in head placement between scans and expressed as
      slopes (cubic centimeters per year), percentage of change over baseline for the
      control subjects, and standardized change for the alcoholic patients. The
      alcoholic patients varied considerably in the percentage of time that symptoms of
      alcohol dependence were present and in the amount of alcohol consumed during
      follow-up. RESULTS: The cortical gray matter diminished in volume over time in
      the control subjects, most prominently in the prefrontal cortex, while the
      lateral and third ventricles enlarged. The alcoholic patients showed similar age
      related changes with a greater rate of gray matter volume loss than the control
      subjects in the anterior superior temporal lobe. The amount of alcohol consumed
      during follow-up predicted the rate of cortical gray matter volume loss, as well
      as sulcal expansion. The rate of ventricular enlargement in alcoholic patients
      who maintained virtual sobriety was comparable to that in the control subjects.
      CONCLUSIONS: During a 5-year period, brain volume shrinkage is exaggerated in the
      prefrontal cortex in normal aging with additional loss in the anterior superior
      temporal cortex in alcoholism. The association of cortical gray matter volume
      reduction with alcohol consumption over time suggests that continued alcohol
      abuse results in progressive brain tissue volume shrinkage.

PMID- 9783562
TI  - Posttraumatic stress disorder and drug disorders: testing causal pathways.
AB  - BACKGROUND: Although there is a high degree of comorbidity between posttraumatic
      stress disorder (PTSD) and drug use disorders, little is known about causal
      relationships between PTSD, exposure to traumatic events, and drug use disorders.
      METHODS: In a longitudinal study in southeast Michigan, 1007 adults aged 21 to 30
      years were initially assessed in 1989 and were followed up 3 and 5 years later,
      in 1992 and 1994. Psychiatric disorders according to DSM-III-R criteria were
      measured by the National Institute of Mental Health Diagnostic Interview
      Schedule. To take into account temporal sequencing, the associations between
      PTSD, traumatic events, and drug use disorders were analyzed by using Cox
      proportional hazards models with time-dependent covariates. RESULTS:
      Posttraumatic stress disorder signaled an increased risk of drug abuse or
      dependence (hazards ratio, 4.5; 95% confidence interval, 2.6-7.6, adjusted for
      sex), whereas exposure to traumatic events in the absence of PTSD did not
      increase the risk of drug abuse or dependence. The risk for abuse or dependence
      was the highest for prescribed psychoactive drugs (hazards ratio, 13.0; 95%
      confidence interval, 5.3-32.0). There was no evidence that preexisting drug abuse
      or dependence increased the risk of subsequent exposure to traumatic events or
      the risk of PTSD after traumatic exposure. CONCLUSION: The results suggest that
      drug abuse or dependence in persons with PTSD might be the inadvertent result of
      efforts to medicate symptoms, although the possibility of shared vulnerability to
      PTSD and drug use disorders cannot be ruled out.

PMID- 9783563
TI  - Intravenous clomipramine for obsessive-compulsive disorder refractory to oral
      clomipramine: a placebo-controlled study.
AB  - BACKGROUND: Uncontrolled reports suggest that intravenous clomipramine
      hydrochloride may be effective for patients with obsessive-compulsive disorder
      (OCD) who are nonresponsive to oral clomipramine. METHODS: Fifty-four patients
      with oral clomipramine-refractory OCD were randomized to receive 14 infusions of
      either placebo or clomipramine hydrochloride, starting at 25 mg/d and increasing
      to 250 mg/d. Ratings were conducted double-blind after infusion 14 among 54
      patients, single-blind 1 week later among 39 patients, and nonblind 1 month later
      among 31 patients. Response was based on a Clinical Global Impressions rating of
      at least "much improved." RESULTS: Six (21%) of 29 patients randomized to receive
      intravenous (i.v.) clomipramine vs 0 of 25 patients given i.v. placebo were
      responders after 14 infusions (df = 1, P<.02). Dimensional ratings after infusion
      14 revealed significant (P = .007) improvement on the National Institute of
      Mental Health-Obsessive-Compulsive Scale and the Clinical Global Impressions
      Scale (P = .03), but not the Yale-Brown Obsessive Compulsive Scale. One week
      later, all dimensional measures of OCD showed significant improvement. At 1 week
      post-i.v., 9 (43%) of 21 patients initially randomized to i.v. clomipramine and
      treated subsequently with oral clomipramine were responders, whereas 0 of 18
      patients initially randomized to receive i.v. placebo and treated subsequently
      with several days of open-label i.v. clomipramine responded (df = 1, P<.002). Of
      the 31 patients assessed 1 month after i.v. infusion (treatment not controlled),
      18 (58.1%) were responders. Intravenous clomipramine treatment was safe with no
      serious adverse consequences. CONCLUSIONS: Intravenous clomipramine is more
      effective than i.v. placebo for patients with OCD with a history of inadequate
      response or intolerance to oral clomipramine. Further study of this promising
      treatment for refractory OCD is needed.

PMID- 9783564
TI  - Alterations in serotonin activity and psychiatric symptoms after recovery from
      bulimia nervosa.
AB  - BACKGROUND: Women with bulimia nervosa (BN) have disturbances of mood and
      behavior and alterations of monoamine activity when they are bingeing and
      purging. It is not known whether these alterations are secondary to pathological
      eating behavior or traits that could contribute to the pathogenesis of BN.
      METHODS: To avoid the confounding effects of pathological eating behavior, we
      studied 30 women after long-term recovery (>1 year with no bingeing or purging,
      normal weight, and regular menstrual cycles) from BN. Subjects were compared with
      31 healthy volunteer women. We assessed psychiatric diagnoses and symptoms to
      determine whether there was any persistent disturbance of behavior after
      recovery. We measured cerebrospinal fluid (CSF) levels of the major metabolites
      of serotonin (5-hydroxyindoleacetic acid [5-HIAA]), dopamine (homovanillic acid
      [HVA]), and norepinephrine (3-methoxy-4-hydroxyphenylglycol [MHPG]) as well as
      hormonal and behavioral response to m-chlorophenylpiperazine (m-CPP), a serotonin
      specific agent. RESULTS: Women who were recovered from BN had mild to moderate
      negative moods and obsessions with perfectionism and exactness and exaggerated
      core eating disorder symptoms compared with healthy volunteer women. Recovered BN
      women had increased levels of CSF 5-HIAA compared with control women (117 +/- 33
      vs 73 +/- 15 pmol/mL; P< or =.001) but normal CSF HVA and MHPG concentrations.
      Recovered BN women had an anxious and disorganized behavioral response to m-CPP
      but a normal hormonal response. CONCLUSIONS: Persistent serotonergic and
      behavioral abnormalities after recovery raise the possibility that these
      psychobiological alterations might be trait-related and contribute to the
      pathogenesis of BN.

PMID- 9783565
TI  - Role of the serotonin transporter promoter polymorphism in anxiety-related
      traits.
AB  - BACKGROUND: The heritability of interindividual variation in anxiety and other
      aspects of personality establishes that variants of genes influence these traits.
      A functional polymorphism in the promoter of the human serotonin transporter gene
      (SLC6A4*C) was identified and found to be linked to an anxiety-related
      personality trait, Neuroticism. The polymorphism affects gene transcription and,
      ultimately, gene function. We have attempted to confirm the role of SLC6A4*C in
      anxiety-related personality traits by sibpair analysis and association studies.
      METHODS: Sibpair linkage analysis and association study were performed in 655
      Finns. The index cases were 182 alcoholic criminal offenders, through which 258
      relatives were ascertained to obtain 366 sibpairs. In addition, 215 unrelated
      population controls were collected. Each individual was psychiatrically
      interviewed, blind-rated for DSM-III-R diagnoses, and assessed with the
      Tridimensional Personality Questionnaire. RESULTS: The sibpair analysis revealed
      a positive linkage between SLC6A4*C and the 2 anxiety-related subdimensions of
      Harm Avoidance: HA1 (Anticipatory Worry) and HA2 (Fear of Uncertainty) (P =
      .003). However, there was no consistent association between SLC6A4*C and any
      Tridimensional Personality Questionnaire trait. CONCLUSIONS: In the present study
      we replicated the relationship of SLC6A4*C to anxiety by sibpair linkage analysis
      but found no evidence of association, raising the question of whether SLC6A4*C
      locus is itself affecting anxiety or is linked to another still unknown
      functional variant.

PMID- 9783566
TI  - Phenotypic and genetic structure of traits delineating personality disorder.
AB  - BACKGROUND: The evidence suggests that personality traits are hierarchically
      organized with more specific or lower-order traits combining to form more
      generalized higher-order traits. Agreement exists across studies regarding the
      lower-order traits that delineate personality disorder but not the higher-order
      traits. This study seeks to identify the higher-order structure of personality
      disorder by examining the phenotypic and genetic structures underlying lower
      order traits. METHODS: Eighteen lower-order traits were assessed using the
      Dimensional Assessment of Personality Disorder-Basic Questionnaire in samples of
      656 personality disordered patients, 939 general population subjects, and a
      volunteer sample of 686 twin pairs. RESULTS: Principal components analysis
      yielded 4 components, labeled Emotional Dysregulation, Dissocial Behavior,
      Inhibitedness, and Compulsivity, that were similar across the 3 samples.
      Multivariate genetic analyses also yielded 4 genetic and environmental factors
      that were remarkably similar to the phenotypic factors. Analysis of the residual
      heritability of the lower-order traits when the effects of the higher-order
      factors were removed revealed a substantial residual heritable component for 12
      of the 18 traits. CONCLUSIONS: The results support the following conclusions.
      First, the stable structure of traits across clinical and nonclinical samples is
      consistent with dimensional representations of personality disorders. Second, the
      higher-order traits of personality disorder strongly resemble dimensions of
      normal personality. This implies that a dimensional classification should be
      compatible with normative personality. Third, the residual heritability of the
      lower-order traits suggests that the personality phenotypes are based on a large
      number of specific genetic components.

PMID- 9783567
TI  - Offspring of depressed mothers.

PMID- 9783568
TI  - German scientists may escape fraud trial.

PMID- 9783569
TI  - Pressure grows for relaxation of French embryo research laws.

PMID- 9783570
TI  - Canada's blood agency up and running.

PMID- 9783571
TI  - French scientist shrugs off winning his second Ig Nobel prize.

PMID- 9783572
TI  - Long-lived, but not 'aged'.

PMID- 9783573
TI  - What's in a name (or a number or a date)?

PMID- 9783574
TI  - The fate of the Neanderthals.

PMID- 9783575
TI  - Titan weather report.

PMID- 9783576
TI  - Molecular endocrinology. Two orphans find a home.

PMID- 9783577
TI  - Floral patterning. A LEAFY link from outer space.

PMID- 9783578
TI  - Ribozyme crevices and catalysis.

PMID- 9783579
TI  - Lunar exploration. Water amongst the rock.

PMID- 9783580
TI  - Receptor that leaves a sour taste in the mouth.

PMID- 9783581
TI  - A genetic framework for floral patterning.
AB  - The initial steps of flower development involve two classes of consecutively
      acting regulatory genes. Meristem-identity genes, which act early to control the
      initiation of flowers, are expressed throughout the incipient floral primordium.
      Homeotic genes, which act later to specify the identity of individual floral
      organs, are expressed in distinct domains within the flower. The link between the
      two classes of genes has remained unknown so far. Here we show that the meristem
      identity gene LEAFY has a role in controlling homeotic genes that is separable
      from its role in specifying floral fate. On the basis of our observation that
      LEAFY activates different homeotic genes through distinct mechanisms, we propose
      a genetic framework for the control of floral patterning.

PMID- 9783582
TI  - Crystal structure of a hepatitis delta virus ribozyme.
AB  - The self-cleaving ribozyme of the hepatitis delta virus (HDV) is the only
      catalytic RNA known to be required for the viability of a human pathogen. We
      obtained crystals of a 72-nucleotide, self-cleaved form of the genomic HDV
      ribozyme that diffract X-rays to 2.3 A resolution by engineering the RNA to bind
      a small, basic protein without affecting ribozyme activity. The co-crystal
      structure shows that the compact catalytic core comprises five helical segments
      connected as an intricate nested double pseudoknot. The 5'-hydroxyl leaving group
      resulting from the self-scission reaction is buried deep within an active-site
      cleft produced by juxtaposition of the helices and five strand-crossovers, and is
      surrounded by biochemically important backbone and base functional groups in a
      manner reminiscent of protein enzymes.

PMID- 9783583
TI  - Transient clouds in Titan's lower atmosphere.
AB  - The 1980 encounter by the Voyager 1 spacecraft with Titan, Saturn's largest moon,
      revealed the presence of a thick atmosphere containing nitrogen and methane (1.4
      and approximately 0.05 bar, respectively). Methane was found to be nearly
      saturated at Titan's tropopause, which, with other considerations, led to the
      hypothesis that Titan might experience a methane analogue of Earth's vigorous
      hydrological cycle, with clouds, rain and seas. Yet recent analyses of Voyager
      data indicate large areas of super-saturated methane, more indicative of dry and
      stagnant conditions. A resolution to this apparent contradiction requires
      observations of Titan's lower atmosphere, which was hidden from the Voyager
      cameras by the photochemical haze (or smog) in Titan's stratosphere. Here we
      report near-infrared spectroscopic observations of Titan within four narrow
      spectral windows where the moon's atmosphere is ostensibly transparent. We detect
      pronounced flux enhancements that indicate the presence of reflective methane
      condensation clouds in the troposphere. These clouds occur at a relatively low
      altitude (15+/-10 km), at low latitudes, and appear to cover approximately 9 per
      cent of Titan's disk.

PMID- 9783584
TI  - Imaging unconscious semantic priming.
AB  - Visual words that are masked and presented so briefly that they cannot be seen
      may nevertheless facilitate the subsequent processing of related words, a
      phenomenon called masked priming. It has been debated whether masked primes can
      activate cognitive processes without gaining access to consciousness. Here we use
      a combination of behavioural and brain-imaging techniques to estimate the depth
      of processing of masked numerical primes. Our results indicate that masked
      stimuli have a measurable influence on electrical and haemodynamic measures of
      brain activity. When subjects engage in an overt semantic comparison task with a
      clearly visible target numeral, measures of covert motor activity indicate that
      they also unconsciously apply the task instructions to an unseen masked numeral.
      A stream of perceptual, semantic and motor processes can therefore occur without
      awareness.

PMID- 9783585
TI  - Local control of information flow in segmental and ascending collaterals of
      single afferents.
AB  - In the vertebrate spinal cord, the activation of GABA(gamma-amino-butyric acid)
      releasing interneurons that synapse with intraspinal terminals of sensory fibres
      leading into the central nervous system (afferent fibres) produces primary
      afferent depolarization and presynaptic inhibition. It is not known to what
      extent these presynaptic mechanisms allow a selective control of information
      transmitted through specific sets of intraspinal branches of individual
      afferents. Here we study the local nature of the presynaptic control by measuring
      primary afferent depolarization simultaneously in two intraspinal collaterals of
      the same muscle spindle afferent. One of these collaterals ends at the L6-L7
      segmental level in the intermediate nucleus, and the other ascends to segment L3
      within Clarke's column, the site of origin of spinocerebellar neurons. Our
      results indicate that there are central mechanisms that are able to affect
      independently the synaptic effectiveness of segmental and ascending collaterals
      of individual muscle spindle afferents. Focal control of presynaptic inhibition
      thus allows the intraspinal branches of afferent fibres to function as a dynamic
      assembly that can be fractionated to convey information to selected neuronal
      targets. This may be a mechanism by which different spinal postsynaptic targets
      that are coupled by sensory input from a common source could be uncoupled.

PMID- 9783586
TI  - Drosophila Tcf and Groucho interact to repress Wingless signalling activity.
AB  - Wingless/Wnt signalling directs cell-fate choices during embryonic development.
      Inappropriate reactivation of the pathway causes cancer. In Drosophila, signal
      transduction from Wingless stabilizes cytosolic Armadillo, which then forms a
      bipartite transcription factor with the HMG-box protein Drosophila Tcf (dTcf) and
      activates expression of Wingless-responsive genes. Here we report that in the
      absence of Armadillo, dTcf acts as a transcriptional repressor of Wingless
      responsive genes, and we show that Groucho acts as a corepressor in this process.
      Reduction of dTcf activity partially suppresses wingless and armadillo mutant
      phenotypes, leading to derepression of Wingless-responsive genes. Furthermore,
      overexpression of wild-type dTcf enhances the phenotype of a weak wingless
      allele. Finally, mutations in the Drosophila groucho gene also suppress wingless
      and armadillo mutant phenotypes as Groucho physically interacts with dTcf and is
      required for its full repressor activity.

PMID- 9783587
TI  - The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional
      repressors.
AB  - Tcf/Lef transcription factors mediate signalling from Wingless/Wnt proteins by
      recruiting Armadillo/beta-catenin as a transcriptional co-activator. However,
      studies of Drosophila, Xenopus and Caenorhabditis elegans have indicated that Tcf
      factors may also be transcriptional repressors. Here we show that Tcf factors
      physically interact with members of the Groucho family of transcriptional
      repressors. In transient transfection assays, the Xenopus Groucho homologue XGrg
      4 inhibited activation of transcription of synthetic Tcf reporter genes. In
      contrast, the naturally truncated Groucho-family member XGrg-5 enhanced
      transcriptional activation. Injection of XGrg-4 into Xenopus embryos repressed
      transcription of Siamois and Xnr-3, endogenous targets of beta-catenin-Tcf.
      Dorsal injection of XGrg-4 had a ventralizing effect on Xenopus embryos.
      Secondary-axis formation induced by a dominant-positive Armadillo-Tcf fusion
      protein was inhibited by XGrg-4 and enhanced by XGrg-5. These data indicate that
      expression of Tcf target genes is regulated by a balance between Armadillo and
      Groucho.

PMID- 9783588
TI  - Androstane metabolites bind to and deactivate the nuclear receptor CAR-beta.
AB  - The orphan receptor CAR-beta binds DNA as a heterodimer with the retinoid-X
      receptor and activates gene transcription in a constitutive manner. Here we show
      that, in contrast to the classical nuclear receptors, the constitutive activity
      of CAR-beta results from a ligand-independent recruitment of transcriptional co
      activators. While searching for potential ligands of CAR-beta, we found that the
      steroids androstanol and androstenol inhibit the constitutive activity of CAR
      beta. This effect is stereospecific: only 3alpha-hydroxy, 5alpha-reduced
      androstanes are active. These androstanes do not interfere with
      heterodimerization or DNA binding of CAR-beta; instead, they promote co-activator
      release from the ligand-binding domain. These androstane ligands are examples of
      naturally occurring inverse agonists that reverse transcriptional activation by
      nuclear receptors. CAR-beta (constitutive androstane receptor-beta), therefore,
      defines an unanticipated steroidal signalling pathway that functions in a manner
      opposite to that of the conventional nuclear receptor pathways.

PMID- 9783589
TI  - A Mec1- and Rad53-dependent checkpoint controls late-firing origins of DNA
      replication.
AB  - DNA replication in eukaryotic cells initiates from many replication origins which
      fire throughout the S phase of the cell cycle in a predictable pattern: some
      origins fire early, others late. Little is known about how the initiation of DNA
      replication and the elongation of newly synthesized DNA strands are coordinated
      during S phase. Here we show that, in budding yeast, hydroxyurea, which blocks
      the progression of replication forks from early-firing origins, also inhibits the
      firing of late origins. These late origins are maintained in the initiation
      competent prereplicative state for extended periods. The block to late origin
      firing is an active process and is defective in yeast with mutations in the rad53
      and mec1 checkpoint genes, indicating that regulation of late origin firing may
      also be an important component of the 'intra-S-phase' checkpoint and may aid cell
      survival under adverse conditions.

PMID- 9783591
TI  - Amifostine in reducing cisplatin toxicity.
AB  - Amifostine has been demonstrated in preclinical evaluation and through the
      conduct of a randomized controlled clinical trial to reduce the incidence and
      severity of cisplatin-associated toxicity. While the role of amifostine in
      standard oncologic management remains to be defined, patients who require
      treatment with cisplatin who have preexisting renal or neurologic dysfunction may
      have their potential for further damage to these organs reduced if amifostine is
      delivered along with the cytotoxic drug.

PMID- 9783590
TI  - Regulation of DNA-replication origins during cell-cycle progression.
AB  - We have shown previously that chromosome VI of Saccharomyces cerevisiae contains
      nine origins of DNA replication that differ in initiation frequency and replicate
      sequentially during the S phase of the cell cycle. Here we show that there are
      links between activation of these multiple origins and regulation of S-phase
      progression. We study the effects of a DNA-damaging agent, methyl methane
      sulphonate (MMS), and of mutations in checkpoint genes such as rad53 on the
      activity of origins, measured by two-dimensional gel analysis, and on cell-cycle
      progression, measured by fluorescence-activated cell sorting. We find that when
      MMS slows down S-phase progression it also selectively blocks initiation from
      late origins. A rad53 mutation enhances late and/or inefficient origins and
      releases the initiation block by MMS. Mutation of rad53 also results in a late
      origin becoming early replicating. We conclude that rad53 regulates the timing of
      initiation of replication from late origins during normal cell growth and blocks
      initiation from late origins in MMS-treated cells. rad53 is, therefore, involved
      in the cell's surveillance of S-phase progression. We also find that orc2, which
      encodes subunit 2 of the origin-recognition complex, is involved in suppression
      of late origins.

PMID- 9783593
TI  - Prevention and treatment of oral mucositis following cancer chemotherapy.
AB  - The administration of many chemotherapy regimens may be complicated by toxicities
      that limit clinicians' abilities to deliver the most effective doses of active
      agents. Oral mucositis remains the dose-limiting toxicity of a variety of
      chemotherapeutic regimens and may result in significant morbidity, impaired
      nutrition, treatment delays, and dose reductions. In this report, the mechanisms
      of both direct and indirect stomatotoxicity are reviewed and efforts are made to
      help identify patient-related and treatment-related factors that predispose
      patients to oral mucositis. Last, various approaches to prevent and treat
      chemotherapy-induced mucositis are reviewed.

PMID- 9783594
TI  - Hematopoietic growth factors in the reduction of chemotherapeutic toxicity.
AB  - Neutropenia is the most common dose-limiting toxicity of conventional
      chemotherapy. The colony-stimulating factors (CSFs), granulocyte (G)-CSF and
      granulocyte-macrophage (GM)-CSF, stimulate proliferation and maturation of
      myeloid progenitors and have been effective in reducing neutropenia and its
      complications. The primary use of CSFs in patients receiving chemotherapy for
      small cell lung cancer has resulted in a reduction in the incidence of febrile
      neutropenia, a decrease in the duration of grade IV neutropenia, and a reduction
      in hospitalization time and antibiotic use. Although CSF use allows for higher
      dose intensity, a survival benefit has not been proven. The use of CSFs after the
      occurrence of neutropenic fever decreases the duration of grade IV neutropenia,
      but effects on hospitalization and antibiotic use are less well-defined. The
      therapeutic use of CSFs in the setting of established neutropenia, regardless of
      the presence or absence of fever, is not supported in the literature. The
      administration of CSFs to patients with acute myeloid leukemia is safe in that no
      trial has demonstrated evidence of leukemic stimulation with these drugs. As in
      other settings, the duration of neutropenia is shortened if CSFs are used
      postchemotherapy with evidence of clinical benefit. CSFs also decrease
      chemotherapeutic toxicity via other mechanisms. The use of G-CSF reduces the
      incidence of mucositis, in normal donors enhances the yield of leukapheresis for
      granulocyte transfusion, and is beneficial in the autologous transplant setting.
      These effects of CSFs in mitigating chemotherapeutic toxicity are reviewed.

PMID- 9783592
TI  - Strategies for reduction of anthracycline cardiac toxicity.
AB  - Anthracyclines are one of the most active classes of antineoplastic compounds.
      The limiting toxicity of this class of drugs is a cumulative, dose-related
      diffuse cardiomyopathy, which occurs in up to 20% of patients with a cumulative
      doxorubicin dose of 450 to 500 mg/m2. Higher incidences of cardiac toxicity have
      more recently been reported when doxorubicin was combined with other agents such
      as paclitaxel. Methods to reduce or prevent this toxicity have been a major area
      of investigation. The use of anthracycline analogs has had limited success.
      Available data using anthracyclines incorporated into liposomes suggest that
      cardiac toxicity is significantly reduced. Dexrazoxane, a bisdioxopiperazine that
      chelates intracellular iron and prevents free radical formation in cardiac
      muscle, has been demonstrated to be cardioprotective in patients receiving
      anthracyclines. This article reviews the data regarding the mechanism of
      anthracycline-induced cardiac toxicity, diagnostic procedures, and methods of
      reducing this toxicity.

PMID- 9783595
TI  - A practitioner's guide to cancer-related alopecia.
AB  - Alopecia due to the side effects of the treatment of cancer is one of the most
      common and emotionally troublesome effects of cancer therapy. Preventive
      measures, primarily scalp hypothermia, can be effective in some cases, but the
      worry of subsequent scalp metastasis remains. Investigative studies in animals
      are hindered by a poor animal alopecia model. Several promising agents require
      translation into clinical practice. Until then, disguising the alopecia with
      wigs, hats, or turbans remains the mainstay of treatment.

PMID- 9783596
TI  - Impact of epoetin alfa in chemotherapy-associated anemia.
AB  - Anemia associated with cancer and cytotoxic chemotherapy contributes adversely to
      the quality of life (QOL) of these patients. RBC transfusions have been the
      traditional treatment, but due to the associated risks, they are not routinely
      used to treat mild and moderate degrees of anemia Therapy with recombinant human
      erythropoietin ([EPO] epoetin alfa) in these patients has been effective for both
      prevention and treatment of anemia, and in decreasing transfusion requirements.
      More importantly, studies have shown that the addition of epoetin alfa therapy to
      the treatment of patients receiving cancer chemotherapy is associated with a
      significant increase in energy level, functional status, and overall QOL. Further
      studies will be required to define the most efficient and cost-effective dose and
      schedule of epoetin alfa during cancer chemotherapy, so that its benefits will be
      available to as many patients as possible. The most important studies will be
      focused on defining the relationship of dose to response, identifying early
      predictors of response, and determining cost-effectiveness.

PMID- 9783597
TI  - Antiemetic therapy.

PMID- 9783598
TI  - Modulation of platinum-induced toxicities and therapeutic index: mechanistic
      insights and first- and second-generation protecting agents.
AB  - Platinum-type drugs have proven to be valuable in the treatment of a variety of
      solid tumors, beginning with the commercial approval of cisplatin 18 years ago.
      There are several clinically important toxicities commonly associated with the
      administration of these drugs. Despite the extensive use of cisplatin and
      carboplatin, the fundamental chemical transformations and mechanisms that
      underlie their antitumor and toxic effects have not been fully characterized.
      Several first-generation protective thiols have been clinically studied in an
      attempt to reduce the toxicity of platinum-type drugs; while some of these agents
      appear to protect against certain toxicities, nearly all platinum-protecting
      drugs have their own intrinsic toxicities, which can be additive to the toxicity
      of platinum-type drugs. Tumor protection by platinum-protecting drugs is an
      additional untoward effect that is associated with certain types of agents and
      must be addressed with care. Recent advances in theoretical and laboratory
      methods and the use of supercomputers have extended our understanding of the
      possible major mechanisms underlying platinum drug antitumor activity and
      toxicity; we present strong evidence that there are two classes of chemical
      species of platinum drug. One class appears to predominantly account for the
      antitumor activity, and the other class of chemical species produces many of the
      toxic effects of platinum drugs. We have discovered a new nontoxic, second
      generation platinum-protecting agent, known as BNP7787, which appears to
      selectively inactivate and eliminate toxic platinum species. BNP7787 has recently
      entered phase I clinical testing in cancer patients.

PMID- 9783599
TI  - Impact of stomach and colon injuries on intra-abdominal abscess and the
      synergistic effect of hemorrhage and associated injury.
AB  - BACKGROUND: Colon wounds are recognized to be highly associated with intra
      abdominal abscess (IAA) after penetrating trauma, whereas gastric wounds are
      thought to contribute minimally to abscess because of the bactericidal effect of
      low pH. This study evaluated the impact of stomach or colon wounds, the
      contribution of other risk factors, and associated abdominal injuries on IAA.
      METHODS: Patients with penetrating colon or stomach wounds during a 10-year
      period were reviewed and stratified by age, Injury Severity Score, transfusions,
      and associated abdominal injuries. Early deaths (<48 hours) from hemorrhage were
      excluded. Outcomes analyzed were IAA and death. RESULTS: A total of 812 patients
      were identified. There were 32 late deaths (4%), of which 28% were attributable
      to IAA and multiple organ failure. IAA rates for isolated stomach or colon wounds
      were 0 and 4.2%, respectively. The presence of associated injuries increased IAA
      rates to 7.5 and 8.8%, respectively. Independent predictors of IAA determined by
      multivariate analysis included age, transfusions, gunshot wounds, and associated
      injuries to the liver, pancreas, and kidney. CONCLUSION: Gastric injuries are
      equivalent to colon wounds in their contribution to IAA. Contamination from
      either organ without associated injury is minimally associated with IAA, but
      injury to both appears synergistic. The immunosuppressive effects of age and
      hemorrhage, in addition to significant associated injury, enhance the development
      of IAA.

PMID- 9783600
TI  - The role of presacral drainage in the management of penetrating rectal injuries.
AB  - PURPOSE: To compare in a randomized, prospective manner infectious complication
      rates associated with presacral drainage versus no drainage in the presence of
      penetrating rectal injury. METHODS: During a 45-month period, 48 patients with
      penetrating rectal injuries were entered into a randomized, prospective study at
      an urban Level I trauma center. The patients were randomized to a presacral
      drainage group or a nondrainage group. Randomization was performed after
      detection of the rectal injury. Forty-four injuries were identified by
      proctoscopy (92%), with the rest detected intraoperatively or by physical
      examination. All patients with rectal injuries were included regardless of age,
      associated injuries, time from injury to operation, blood loss, severity of
      rectal injury, other abdominal organs injured, or hemodynamic stability. Rectal
      injuries were defined as those injuries to the large bowel distal to the
      peritoneal reflection. All rectal injuries underwent fecal diversion, and all
      drainage was accomplished using closed Jackson-Pratt drainage. RESULTS: Forty
      eight patients were studied, of whom 25 were randomized to no drainage and 23
      were randomized to presacral drainage. The average age for the nondrainage group
      was 21.9 years, and the average age for the presacral drainage group 26.0 years.
      The average Penetrating Abdominal Trauma Index score was 34.3 for the nondrainage
      group and 32.4 for the presacral drainage group. There were two (8%) septic
      complications (one perirectal and one perivesical abscess) associated with the
      rectal injuries in the presacral drainage group. The abscesses in the drainage
      group resolved after computed tomography-guided drainage. There was one (4%)
      septic complication (rectocutaneous fistula) in the nondrainage group, which was
      associated with a retained missile fragment. The fistula resolved after bedside
      percutaneous removal of the missile fragment. CONCLUSION: We conclude that
      presacral drainage for penetrating rectal injuries has no effect on infectious
      complications associated with the rectal injuries.

PMID- 9783601
TI  - Hemostatic efficacy of a fibrin sealant dressing in an animal model of kidney
      injury.
AB  - OBJECTIVE: The purpose of this study is to determine the hemostatic efficacy of a
      fibrin sealant dressing compared with a standard collagen control dressing in an
      animal model of kidney injury. METHODS: Twenty adult male Sprague-Dawley rats
      were administered general anesthesia and underwent partial nephrectomy with
      heparin anticoagulation (300 U/kg intravenous). Treatment of the cut surface of
      the kidney was randomized to three groups: group I, no hemostatic agent; group
      II, collagen dressing; and group III, fibrin sealant dressing. RESULTS: Blood
      loss was significantly less in group III (3.39+/-0.63 mL) than in group I (8.64+/
      2.26 mL) and group II (8.63+/-1.72 mL; p < 0.001). The percentage decrease in the
      mean arterial pressure was significantly less in group III (34.09+/-15.58%) than
      in group I (59.66+/-16.19%) and group II (60.35+/-15.66%; p=0.015). CONCLUSION:
      Fibrin sealant dressings provide effective hemostasis and are superior to
      collagen dressings in an animal model of kidney injury. Additional development of
      fibrin sealant dressings for potential clinical use is warranted.

PMID- 9783602
TI  - Fibrin glue terminates massive bleeding after complex hepatic injury.
AB  - OBJECTIVE: We determined the ability of a packaged fibrin glue (FG) product to
      terminate severe bleeding in a new porcine model of complex hepatic injury.
      METHODS: Femoral arterial and venous catheters were placed in pentobarbital
      anesthetized swine (n=7 per group, 16-18 kg). Pigs received an external blast to
      the right upper abdomen at 0 minutes, followed by uncontrolled hemorrhage at 0 to
      30 minutes, with anticoagulation (heparin, 200 U/kg) at 10 minutes. Pigs were
      resuscitated with lactated Ringer's solution (20 mL/kg) beginning at 15 minutes
      and then underwent laparotomy to control bleeding at 30 minutes. Lactated
      Ringer's solution was infused to keep mean arterial pressure greater than 70 mm
      Hg until 120 minutes, when repeat laparotomy was performed. Control animals
      (group 1) underwent routine surgical procedures to terminate bleeding followed by
      packing if hepatic bleeding continued. The FG animals (group II) underwent
      routine surgical procedures plus application of FG. Avoidance of packing,
      estimated blood loss (EBL) during and after laparotomy, and fluid resuscitation
      volume were the primary end points studied. RESULTS: In both groups, mean
      arterial pressure varied significantly from baseline to 120 minutes (group I:
      100+/-3 to 52+/-11 mm Hg; group II: 99+/-4 to 66+/-3 mm Hg). Temperature
      decreased at the end of each experiment (group I: 37+/-1 to 33+/-1 degrees C;
      group II: 37+/-1 to 34+/-1 degrees C). There were no group differences in EBL
      before laparotomy (0-30 minutes), but from initial laparotomy to repeat
      laparotomy (30-120 min), EBL (group I: 875+/-265 mL; group II: 300+/-59 mL) and
      total fluid resuscitation (group I: 2.9+/-0.4 L; group II: 1.9+/-0.3 L) were
      statistically significantly less in FG pigs. Of greatest importance, six of seven
      control pigs required packing, but none of the FG animals were packed and none
      bled at repeat laparotomy. CONCLUSION: FG stopped bleeding and eliminated the
      need for packing in a model of severe liver injury. Further work in the clinical
      arena is warranted to determine the potential benefits of FG in arresting
      hemorrhage in hypotensive, hypothermic, coagulopathic trauma patients with
      complex visceral injuries.

PMID- 9783603
TI  - Delayed hemothorax after blunt thoracic trauma: an uncommon entity with
      significant morbidity.
AB  - OBJECTIVE: To describe the nature of delayed hemothorax occurring after blunt
      thoracic trauma and to identify the population at risk for this complication.
      METHODS: A retrospective review was conducted of 36 consecutive patients with
      hemothorax consequent to blunt trauma. Criteria for the definition of delayed
      hemothorax were established involving normal interval chest radiographs or
      computed tomographic scans during hospitalization. RESULTS: Twelve cases of
      delayed development of hemothorax were identified. Ninety-two percent of cases
      occurred in patients with multiple or displaced rib fractures. Presentation
      occurred from 18 hours to 6 days after injury. Eleven of the 12 cases were
      heralded by a prodrome of new pleuritic chest pain and dyspnea that occurred from
      4 to 19 hours before treatment. CONCLUSION: Delayed hemothorax after blunt trauma
      is a unique entity occurring in patients with multiple or displaced rib
      fractures. Vigilance for the recognizable prodrome in the high-risk population
      should allow early remediation of this complication.

PMID- 9783604
TI  - Is tension pneumothorax a threat in trauma laparoscopy?
AB  - BACKGROUND: Tension pneumothorax is a reported risk with pneumoperitoneum in the
      presence of diaphragmatic injuries. A goat model with and without diaphragmatic
      injury was used to determine if varying levels of intra-abdominal pressure (IAP)
      result in tension pneumothorax. METHODS: Twenty-four goats were divided equally
      into four groups: (1) 5 mm Hg IAP control, (2) 15 mm Hg IAP control, (3) 5 mm Hg
      IAP with diaphragmatic injury, (4) 15 mm Hg IAP with diaphragmatic injury. Chest
      x-ray films were made and heart rate (HR), mean arterial pressure, central venous
      pressure (CVP), arterial blood gases, and airway pressure (AP) were measured at
      10-minute intervals up to 30 minutes. Significant changes were determined by
      using the one-way analysis of variance and Mann-Whitney test with alpha set at p
      < 0.05. RESULTS: In group 4, 100% (all six goats) developed radiographic evidence
      of tension pneumothorax by 10 minutes. Mean changes from baseline at 20 minutes
      for the following parameters were all significantly different from controls: HR
      (p < 0.05), CVP (p < 0.0001), PaO2 (p < 0.001), and AP (p < 0.004). Mortality was
      67% (four of six) at 25 minutes. In group 3, 100% (all six goats) of the animals
      developed radiographic evidence of a simple pneumothorax without mediastinal
      shift. In this group, there were significant changes in PaO2 (p < 0.003), AP (p <
      0.04), and HR (p < 0.05). Mortality was 16% (one of six) at 25 minutes.
      CONCLUSION: In this goat model of diaphragmatic injury, tension pneumothorax is a
      significant threat when pneumoperitoneum is maintained at 15 mm Hg IAP.
      Pneumoperitoneum at 5 mm Hg IAP leads to simple pneumothorax with deleterious
      effects on oxygenation. Changes in AP, CVP, HR, and PaO2 provide early clues to
      the development of the problem.

PMID- 9783605
TI  - Lipopolysaccharide pretreatment produces macrophage endotoxin tolerance via a
      serum-independent pathway.
AB  - BACKGROUND: Lipopolysaccharide activation (LPSa) of macrophages is thought to
      occur via a CD14-dependent mechanism with a requirement for the serum factor,
      lipopolysaccharide binding protein. LPS-stimulated, CD14-dependent signal
      transduction is associated with phosphorylation of mitogen-activated protein
      kinase (MAPK), nuclear factor-kappaB (NF-kappaB) translocation, and secretion of
      tumor necrosis factor (TNF) and interleukin-1 (IL-1). Macrophage endotoxin
      tolerance after low-dose LPS pretreatment (LPSp) is characterized by inhibition
      of LPSa-stimulated TNF and augmentation of IL-1 secretion. We sought to determine
      the role of CD14-dependent pathways in the induction of endotoxin tolerance by
      comparing the effects of LPSp in the presence or absence of serum. METHODS:
      Murine peritoneal macrophages were exposed to a range of LPSp concentrations in
      the presence or absence of serum. MAPK activation and NF-kappaB were assayed 30
      minutes after LPSp stimulation. TNF production and IL-1 were measured 6 hours
      after stimulation with 100 ng/mL LPSa, with or without 24-hour 10 ng/mL LPSp.
      RESULTS: In the presence of serum, 100 ng/mL LPSp activated MAPK and NF-kappaB,
      whereas no activation of MAPK or NF-kappaB was seen at this LPSp concentration in
      the absence of serum. The absence of serum during 10 ng/mL LPSp did not prevent
      LPSp-mediated inhibition of TNF secretion, and it significantly augmented IL-1
      secretion after stimulation with 100 ng/mL LPSa in the presence of serum.
      CONCLUSION: Induction of the alterations in subsequent LPSa-stimulated cytokine
      secretion characteristic of endotoxin tolerance by LPSp occurs via a serum
      independent signal transduction pathway.

PMID- 9783606
TI  - Timing of vaccination does not affect antibody response or survival after
      pneumococcal challenge in splenectomized rats.
AB  - BACKGROUND: Pneumococcal vaccination after splenectomy for trauma decreases the
      incidence of overwhelming postsplenectomy infection. The optimal timing of
      vaccination has not been established. This study was conducted to determine
      whether timing of vaccination after splenectomy affects antibody response or
      survival after pneumococcal challenge. METHODS: Sprague-Dawley rats were used for
      all experiments. Control rats (n=30) were divided into three equal groups and
      underwent splenectomy followed by sham vaccination 1, 7, or 42 days after
      splenectomy. Treated rats (n=66) were divided into three equal groups and
      underwent splenectomy followed by vaccination with polyvalent pneumococcal
      vaccine 1, 7, or 42 days after splenectomy. All rats then underwent
      intraperitoneal Streptococcus pneumoniae inoculation with the predetermined
      lethal dose for 50% of the population 10 days after vaccination. Rats were
      observed for a 72-hour period after inoculation, and mortality was recorded.
      Immunoglobulin G and immunoglobulin M antibody titers were determined before
      vaccination and before inoculation to determine antibody response. RESULTS:
      Mortality was greater in the control group than in the treatment group (21 of 30
      [70%] vs. 2 of 64 [3%]; p < 0.01). There were no differences in mortality within
      either the control group (1 day, 6 of 10; 7 days, 7 of 10; 42 days, 8 of 10;
      p=0.62) or the treatment group (1 day, 0 of 21; 7 days, 0 of 21; 42 days, 2 of
      22; p=0.14). Immunoglobulin G and immunoglobulin M antibody responses were
      greater in vaccinated than in nonvaccinated rats. There was no effect of timing
      of vaccination on antibody response. CONCLUSION: Pneumococcal vaccine reduces
      mortality from postsplenectomy infection. Timing of vaccination after splenectomy
      does not affect survival from a pneumococcal challenge or antibody response in
      rats. This study supports the practice of administering vaccine within 24 hours
      of splenectomy when vaccine cannot be administered before surgery.

PMID- 9783607
TI  - Evaluation of troponin-I as an indicator of cardiac dysfunction after thermal
      injury.
AB  - BACKGROUND: Biochemical serum markers commonly used to assess human cardiac
      injury (creatinine phosphokinase, creatine phosphokinase-MB) have been shown to
      have diminished specificity for detection of cardiac injury in the setting of
      burn-related soft-tissue and skeletal muscle injury. Laboratory studies have
      demonstrated that severe cutaneous thermal injury is associated with cardiac
      contractile dysfunction and a corresponding elevation in serum cardiac troponin-I
      (cTn-I) in several species. METHODS: Twenty-three patients admitted to a tertiary
      care burn referral center were evaluated. Patients were monitored with pulmonary
      artery catheters, and creatinine phosphokinase, creatine phosphokinase-MB, and
      cTn-I levels were determined for 24 hours. Using a database, 6,722 burn patients
      were reviewed to determine the incidence of preexisting cardiac disease and
      postburn cardiac complications. RESULTS: All patients had persistent sinus
      tachycardia (>115 beats per minute) without obvious electrical anomalies. All
      patients centrally monitored with a pulmonary artery catheter (n=20) maintained a
      cardiac index of greater than 3.0 L x min(-1) x m(-2) x cTn-I was present (>0.3
      ng/mL) within 3.0 hours and elevated (>0.55 ng/mL) at 24 hours for all burns of
      more than 18% total body surface area. Historically, although only 5% of all
      admissions manifest acute postburn cardiac complications, 94% of these patients
      presented with preexisting heart disease. CONCLUSION: Severe thermal injury was
      associated with a mild elevation in serum troponin-I; however, this did not
      correlate with overt cardiac morbidity or mortality. Postburn elevation of cTn-I
      suggested that a subtle degree of cardiac injury was present after a severe
      thermal injury despite hyperdynamic cardiac function during resuscitation.

PMID- 9783608
TI  - Decreased soluble adhesion molecule L-selectin plasma concentrations after major
      trauma.
AB  - BACKGROUND: Binding of the leukocyte glycoprotein L-selectin to ligands expressed
      by activated endothelium directs leukocyte recruitment to areas of acute
      inflammation. Sequestration by activated microvascular endothelium has been
      proposed to explain the low plasma concentrations of soluble L-selectin (sCD62L)
      observed early in patients with acute respiratory distress syndrome. We
      hypothesized that inflammatory endothelial activation may occur in trauma
      patients, leading to decreased sCD62L plasma concentrations. METHODS: This study
      was a prospective analysis of sCD62L plasma concentrations in patients with
      isolated head injuries and multiple trauma patients without head injuries
      admitted to two tertiary-level intensive care units. sCD62L plasma concentrations
      were determined in 18 consecutive adult patients with isolated moderate and
      severe head injuries and in 13 multiple trauma patients without head injuries
      immediately upon admission to the intensive care unit and then daily for up to 10
      days after trauma. RESULTS: Compared with healthy adult controls (n=22), patient
      sCD62L plasma concentrations were significantly decreased upon admission (5.7+/
      1.6 vs. 11.0+/-1.7 pmol/mL; p < 0.001). In all patients, sCD62L concentrations
      remained depressed throughout the study period. sCD62L concentrations did not
      differ significantly between patients with isolated head injuries and multiple
      trauma patients without head injuries, although repeated-measures analysis of
      variance showed significantly more depressed sCD62L concentrations associated
      with severe (n=14) compared with moderate head injuries (n=4) during the study
      period (p < 0.05). CONCLUSION: Patients with major trauma present with a
      significant reduction of sCD62L plasma concentrations within the first 12 hours
      after trauma and during subsequent intensive care. This finding suggests
      widespread microvascular endothelial activation after trauma, which may be
      associated with increased neutrophil extravasation.

PMID- 9783609
TI  - Contusion of skeletal muscle increases leukocyte-endothelial cell interactions:
      an intravital-microscopy study in rats.
AB  - OBJECTIVE: To investigate the relationship between secondary muscle damage after
      contusion and the interactions between leukocytes and endothelial cells, which
      are essential steps in secondary inflammatory response. METHODS: In a randomized
      animal study, rats were chronically instrumented with dorsal skinfold
      microvascular chambers and exposed to standardized contusion or sham contusion.
      Leukocyte rolling and adherence in postcapillary venules before and after muscle
      contusion or sham contusion were quantitated using in vivo microscopy. RESULTS:
      The number of rolling leukocytes in the postcapillary venules before contusion
      was low. At 300 minutes after contusion, the number of rolling and adherent
      leukocytes in the striated muscle microvasculature was increased significantly (p
      < or = 0.05) compared with either the baseline precontusion condition or the
      control group at the same time. CONCLUSION: In the mid-term to long-term stages
      of skeletal muscle injury associated with contusion, a significant portion of
      tissue damage is secondary to leukocyte-endothelial cell interactions.

PMID- 9783610
TI  - Effects of local cooling on microvascular hemodynamics and leukocyte adhesion in
      the striated muscle of hamsters.
AB  - OBJECTIVES: Cellular metabolism is dependent on the local temperature in tissues.
      Induced hypothermia has been shown to be protective in a number of conditions,
      especially traumatic, ischemic, burn, and neurological injury. However, the
      protective mechanisms of cold therapy remain controversial and the hemodynamic
      changes in the microcirculation of striated muscles in response to hypothermia
      have not been studied in detail previously. METHODS: In this study, we
      investigated the microvascular response of local cooling and rewarming in the
      striated muscle of hamsters by use of the dorsal skinfold preparation and in vivo
      fluorescence microscopy. RESULTS: We found that reduction of the surface
      temperature to 8 degrees C for 30 minutes caused arteriolar vasoconstriction with
      a decrease in diameters by 43+/-7% while the venular and capillary diameters
      remained unchanged. The cooling procedure also markedly reduced the functional
      capillary density and the blood flow velocity and diameters in all vessel types,
      i.e., arterioles, venules, and capillaries. Moreover, the percentage of
      capillaries with no flow increased from 0.4+/-0.5% to 44+/-14% after 10 minutes
      of cold therapy. However, these hemodynamic changes induced by local hypothermia
      were completely reversed to the precooling values after termination of cooling
      and 30 min of rewarming. Strikingly, we found no increase in the number of
      adherent leukocytes and vascular permeability after the cooling and rewarming
      period, while, in contrast, additional experiments with warm ischemia (30
      minutes) and reperfusion (30 minutes), i.e., reduced microvascular perfusion and
      reperfusion at normothermia, caused a sustained decrease in local perfusion and a
      nine-fold increase in venular leukocyte adhesion. CONCLUSIONS: Taken together,
      our functional data demonstrate that hypothermia markedly reduces microvascular
      perfusion, which is completely restored upon rewarming. The reduced microvascular
      perfusion during hypothermia did not provoke an inflammatory response, whereas
      leukocyte recruitment was prominent after reduced perfusion at normothermia,
      indicating that transient hypothermia has no adverse effects on microvascular
      parameters in the striated muscle in vivo.

PMID- 9783611
TI  - Coagulatory response after femoral instrumentation after severe trauma in sheep.
AB  - OBJECTIVE: Pulmonary complications after intramedullary femoral nailing have been
      attributed to bone marrow fat embolization and a variety of cascade effects. We
      investigated whether the coagulatory response after intramedullary femoral
      nailing in merino sheep is altered after severe trauma. METHODS: Adult merino
      sheep were submitted to hemorrhagic shock (2 hours, 50 mm Hg) and unilateral lung
      contusion. After recovery (day 3 of the study), reamed femoral intramedullary
      nailing (RFN), unreamed femoral intramedullary nailing (UFN), or plate
      osteosynthesis of the femur (P) was performed. Pulmonary artery pressure, central
      venous levels of factor V, protein C, antithrombin III, and fibrinogen, were
      determined. At 1 and 3 days before and after femur instrumentation, pulmonary
      capillary permeability was assessed on the basis of the comparative albumin
      content in bronchoalveolar lavage fluid. RESULTS: Group RFN, n=8; group UFN, n=7;
      group P, n=6. A significant (p < 0.05) postoperative increase in the relative
      albumin content in terms of the BAL/plasma albumin ratio was measured in group
      RFN (day 3 preoperatively: 0.38+/-0.05 day 3 postoperatively: 0.53+/-0.06, p <
      0.05 (RFN vs. P), which contrasted with group UFN (day 3 preoperatively: 0.44+/
      0.09, day 3 postoperatively: 0.46+/-0.09, no significant difference). This
      evidence of increased pulmonary permeability occurred in association with
      evidence of increased activation of coagulation factors (data presented as
      percentage of day 3 preoperative baseline values). The data for fibrinogen (15
      min postoperatively) is as follows: group RFN, 74+/-9% (p < 0.05 vs. P); group
      UFN, 83+/-8% (not significant); group P, 98+/-6%. The data for antithrombin III
      (15 min. postoperatively) is as follows: group RFN, 72+/-6% (p < 0.05 vs. P);
      group UFN, 79+/-8% (not significant); group P, 92+/-8% (not significant).
      CONCLUSION: After severe trauma, an increase of pulmonary permeability after
      reamed femoral nailing was associated with increased consumption of coagulation
      factors. After unreamed nailing, a similar trend was apparent, but this was not
      found to be statistically significant. These data provide support for the theory
      that after severe trauma, unreamed femoral nailing reduces but does not abolish
      pulmonary sequelae when compared with reamed femoral nailing.

PMID- 9783612
TI  - Subtalar distractional realignment arthrodesis with wedge bone grafting and
      lateral decompression for calcaneal malunion.
AB  - BACKGROUND: The purpose of this study was to evaluate prospectively the efficacy
      of subtalar distractional realignment arthrodesis in the treatment of calcaneal
      malunion associated with subtalar arthritis, collapse of height, talonavicular
      subluxation, malalignment of the heel axis, and widening heel with
      calcaneofibular abutment. METHODS: Thirty-four patients with severe calcaneal
      malunion were treated with a lateral approach, lateral decompression, medial
      subtalar capsulotomy, and distraction and realignment of the subtalar joint with
      an anteriorly and laterally tapered wedge bone graft. The patients were evaluated
      with a functional rating scale and radiographs, both before and after surgery.
      RESULTS: Thirty-two of the 34 patients were evaluated at a mean of 71 months
      (range, 60-92 months) after the arthrodesis. Solid subtalar fusion was achieved
      in 31 of the 32 patients. The average gain of subtalar distraction was 12 mm.
      Neutral or mild valgus alignment was achieved in 26 of the 32 patients. The mean
      postoperative score (83) showed significant improvement over the mean
      preoperative score (47). Overall, the functional rating scale revealed excellent
      or good results in 26 patients and fair results in 6 patients. CONCLUSION:
      Coupled with wedge bone grafting, the subtalar distractional realignment
      arthrodesis achieved restoration of hindfoot height and axial alignment with a
      good union rate and significant improvement in the majority of patients with
      calcaneal malunion.

PMID- 9783614
TI  - The effect of unreamed and reamed intramedullary nailing on the urinary excretion
      of prostacyclin and thromboxane A2 metabolites in patients with tibial shaft
      fractures.
AB  - OBJECTIVE: To compare the effects of unreamed and reamed intramedullary nailing
      on the systemic production of prostacyclin and thromboxane A2 as assessed,
      respectively, by determinations of urinary 2,3-dinor-6-ketoprostaglandin F1alpha
      and 11-dehydrothromboxane B2 excretion. METHODS: Ten otherwise healthy patients
      with closed and simple tibial shaft fractures were treated with unreamed
      intramedullary nailing, and 10 otherwise healthy patients with closed and simple
      tibial shaft fractures were treated with reamed intramedullary nailing. Urine was
      collected preoperatively and during the next 5 postoperative days. The samples
      were stored at -70 degrees C until assayed at the end of the study. RESULTS: In
      the unreamed group, urinary 2,3-dinor-6-ketoprostaglandin F1alpha and 11
      dehydrothromboxane B2 excretion remained stable and at a significantly lower
      levels compared with the reamed group during the entire study period (p < 0.021).
      In the reamed group, the alteration in urinary 2,3-dinor-6-ketoprostaglandin
      F1alpha excretion preoperatively and on the first postoperative day was nearly
      significant (p=0.075), and the increase in urinary 11-dehydrothromboxane B2
      excretion was significant (p=0.020). The proportional increase compared with
      baseline, however, was 1.6 times greater for 11-dehydrothromboxane B2 than for
      2,3-dinor-6-ketoprostaglandin F1alpha. CONCLUSION: Only reamed intramedullary
      nailing elevates urinary 2,3-dinor-6-ketoprostaglandin F1alpha and 11
      dehydrothromboxane B2 concentrations and their ratio (thromboxane A2/prostacyclin
      production) in patients with simple tibial shaft fractures.

PMID- 9783613
TI  - Pulmonary and systemic fat embolization after medullary canal pressurization: a
      hemodynamic and histologic investigation in the dog.
AB  - BACKGROUND: The potential to produce fat embolism may be important in determining
      the ideal method and timing of fracture treatment in patients with preexisting
      lung injury. METHODS: Four dogs underwent femoral and tibial canal reaming and
      pressurization. Blood gas samples were analyzed, and pulmonary arterial pressure
      was monitored at 1 and 72 hours. Animals were killed 72 hours postoperatively,
      and the lungs, kidneys, and brain were examined histologically and compared with
      equivalent specimens from four control dogs that had not undergone femoral and
      tibial canal reaming and pressurization. RESULTS: Postmortem, intravascular fat
      persisted for 72 hours after induction of pulmonary fat embolism. Mean PaO2 was
      unchanged from baseline at 72 hours after canal pressurization. Canal
      pressurization caused a sustained increase in pulmonary arterial pressure
      (p=0.02) for 1 hour after canal pressurization. The mean pulmonary edema score at
      72 hours was 29+/-3. Only a scant polymorph infiltrate (zero to two polymorphs
      per high-power field) was present at any time. No hyaline membranes were seen at
      any time. The percentage area occupied by intravascular fat in the lungs was
      0.0214+/-0.0058 at 72 hours. No signs of ischemia or inflammation were seen in
      either the cerebral or the renal specimens. CONCLUSION: This study is the first
      to show that intravascular fat persists in the lungs, kidneys, and brain for 72
      hours after canal pressurization and, by itself, does not cause pathologic
      evidence of acute inflammation.

PMID- 9783615
TI  - Augmentative plate fixation for the management of femoral nonunion with broken
      interlocking nail.
AB  - Five patients with femoral nonunion and a broken interlocking nail were treated
      with the augmentative plating procedure. This group included two male and three
      female patients whose average age was 25 years (range, 21-35 years). All of the
      injuries resulted from traffic accidents and were closed fractures. Four of the
      injuries were initially managed with a Grosse-Kempf interlocking nailing system,
      and one case was managed with an AO interlocking nailing system. The broken
      interlocking nail was left in place in situ, and an augmentative plate fixation
      was applied to the fracture site to provide a rigid fixation. Simultaneous bone
      grafting was performed in three of the patients to repair the bony defect. All of
      these patients walked bearing full weight on the extremity without aching at the
      fracture site within 3 months, and all of these five fractures obtained a bony
      union within an average of 5.4 months after this treatment. From our experience,
      we have found this method to be a useful treatment for the nonunion of femoral
      shaft fracture with a broken interlocking nail.

PMID- 9783616
TI  - Kapandji pinning or closed reduction for extra-articular distal radius fractures.
AB  - In a randomized prospective trial, closed reduction and plaster application was
      compared with Kapandji pinning. Closed reduction and plaster cast application was
      performed in 50 patients, Kapandji pinning in 48 patients. According to the
      Cooney score, good and excellent results were found in 74% of patients in the
      closed reduction and plaster cast group compared with 75% of patients in the
      Kapandji-pinning group. In terms of maintenance of reduction and functional
      outcome at 1-year follow-up, no statistically significant differences were found
      between the two groups. We conclude, therefore, that both techniques can be
      applied to extra-articular fractures of the distal radius according to the
      characteristics of the forearm and the surgeon's or the patient's need.

PMID- 9783617
TI  - Management of small infected tibial defects with antibiotic-impregnated autogenic
      cancellous bone grafting.
AB  - Between January of 1991 and December of 1993, 36 patients who had tibia fractures
      complicated by small infected tibia defects were treated at the authors' service.
      The group included 30 men and 6 women whose average age was 36.5 years (range, 18
      72 years). The average follow-up period was 3.7 years. By using the Cierney-Mader
      staging classification of chronic osteomyelitis, 26 of 36 patients (72%) were
      stage 4A and 10 of 36 patients (28%) were stage 4B. Ten patients required muscle
      transfer. All patients were treated with a two-stage protocol. In the first
      stage, antibiotic-impregnated polymethylmethacrylate bead chains were used to
      obliterate the debrided osseous defect. In the second stage, the beads were
      removed, and the defects were reconstructed with antibiotic-impregnated autogenic
      cancellous bone graft. The time between the first and second stage was 2 to 8
      weeks for patients without muscle transfer and 8 to 12 weeks for the patients
      with muscle transfer. The bone defects ranged from 2 to 4 cm. Wound healing and
      bony union were achieved in all patients. Only two patients had recurrent
      infections. The infection arrest rate was 94.4%. Minor pin tract infection of the
      external skeletal fixation was seen in two patients. Two patients developed skin
      rashes secondary to antibiotic therapy. Radiographs at an average follow-up of
      3.7 years showed good consolidation and hypertrophy of grafted bones in all
      patients. After 3 to 5 years of follow-up, our results suggest that the use of
      impregnating antibiotics have no adverse effects on autogenic cancellous bone
      graft incorporation and may help to eliminate infection. This treatment protocol
      provided rapid recovery from osteomyelitis. The use of antibiotic-impregnated
      autogenic bone graft seems to be an effective and safe method for the management
      of small infected tibial defects.

PMID- 9783618
TI  - S-100 serum levels after minor and major head injury.
AB  - BACKGROUND: S-100, a protein of astroglial cells, is described as a marker for
      central nervous system damage. The aim of this study was to evaluate whether the
      marker could give information about the severity and possibility of functional
      recovery after minor and severe head injury. METHODS: Thirty patients after
      severe head injury (Glasgow Coma Scale score < 9) and 11 patients after minor
      head injury (Glasgow Coma Scale score > 12) were included. In each case, blood
      samples were drawn within 6 hours after injury. Outcome was estimated at hospital
      discharge using the Glasgow Outcome Scale. RESULTS: All patients who sustained
      minor head injury had reached a favorable outcome by the time they were
      discharged from the hospital. Their mean S-100 serum level was 0.35 microg/L.
      Patients who sustained severe head injury and were classified as having an
      unfavorable outcome (31%) showed a mean serum concentration of 4.9 microg/L,
      whereas patients classified as having a favorable outcome (69%) had a mean S-100
      level of 1.2 microg/L. All groups differed significantly (p < 0.05). CONCLUSION:
      S-100 appears to be a promising marker for the severity of head injury and
      neuronal damage.

PMID- 9783619
TI  - The use of bedside fluoroscopy to evaluate the cervical spine in obtunded trauma
      patients.
AB  - BACKGROUND: Recognition of a cervical spine injury is important to prevent
      further injury and in planning for future care. The management of the patient
      with a possible cervical spine injury who remains unresponsive is controversial.
      METHODS: A retrospective evaluation of obtunded trauma patients admitted to the
      surgical intensive care unit who underwent bedside fluoroscopic cervical spine
      evaluation. Fluoroscopic findings and all complications were noted. RESULTS:
      Twenty obtunded patients with possible cervical spine injuries underwent bedside
      fluoroscopic cervical spine evaluation. All patients had at minimum a normal
      three-view cervical spine series before fluoroscopy. Thirteen patients (65%) had
      the fluoroscopic examination completed at the bedside and were cleared. The
      complete cervical spine could not be evaluated in six patients (30%). One patient
      (5%) was found to have a C4-5 subluxation in the bedside examination. None of the
      patients had progression of their neurologic symptoms after cervical spine
      flexion/extension, and none developed evidence of spinal cord injury after being
      cleared during their hospital course. Cervical collars remained in place for
      5.7+/-1.41 days (range, 1- 26 days). Three patients (15%) were noted to have
      decubiti under the cervical collar. CONCLUSION: In this small study, the use of
      bedside fluoroscopy to evaluate the cervical spine appears safe and easy to
      perform. One unrecognized injury was identified. The technique is usually
      successful and gives reassurance that a significant cervical spine injury is not
      present.

PMID- 9783620
TI  - Quality assessment of the management of road traffic fatalities at a level I
      trauma center compared with other hospitals in Victoria, Australia. Consultative
      Committee on Road Traffic Fatalities in Victoria.
AB  - OBJECTIVES: Since 1992, the Consultative Committee on Road Traffic Fatalities in
      Victoria, Australia, has identified problems including those contributing to
      death and the potential preventability of deaths in road fatalities who survived
      until at least the arrival of ambulance services. The present analysis examines
      the outcomes at a Level I trauma center compared with other hospital groups in
      Victoria. METHODS: Between 1992 and 1994, 257 consecutive eligible fatalities
      were evaluated. Problems in management and preventable deaths were identified at
      the trauma center (TC) and in pooled data from other hospital groups, i.e.,
      specialist teaching (Level II), other metropolitan (Level III), large regional
      (Level III), and small regional hospitals. RESULTS: Mean problems identified and
      those contributing to death (controlled for the number of areas of care), were
      less frequent at TC (1.7 and 0.6) than at other hospital groups (specialist
      teaching, 1.9 and 1.1*; metropolitan, 3.1* and 1.6*; large regional, 3.8* and
      1.8*; small regional, 5.1* and 2.6*) (*p < 0.05 compared with TC). Preventable
      and potentially preventable deaths were also less common at TC (20%) than at the
      other hospital groups (specialist teaching, 40%*; metropolitan, 41%*; large
      regional, 53%*; small regional, 62%*) (*p < 0.05 compared with TC). When a Trauma
      and Injury Severity Score of 75% or more was used to define preventable death, a
      similar trend was identified. CONCLUSION: Management of patients with major
      trauma at a Level I trauma center was associated with fewer problems contributing
      to death and fewer preventable and potentially preventable deaths than at the
      different hospital groups. A trauma system in Victoria, including bypass of major
      trauma patients to designated hospitals with 24-hour trauma services, is likely
      to decrease the frequency of problems, including the preventable death rates.

PMID- 9783621
TI  - Auto theft-related trauma.
AB  - OBJECTIVE: To determine the medical consequences and economic impact of caring
      for patients injured after motor vehicle crashes (MVC) involving stolen cars.
      METHODS: Presented is a case series of inpatients injured secondary to a MVC
      involving a stolen car from January of 1993 to December of 1994 and treated at a
      university Level I trauma center in Newark, New Jersey. During the time period of
      the study, 1,232 patients (either as the driver or passenger) were admitted after
      a MVC, 115 patients (8%) were identified as sustaining injuries secondary to a
      MVC involving a stolen car. Injuries after car theft represent 8% of all MVC
      related admissions. Data collected included demographics, types of injuries,
      surgical intensive care unit and hospital lengths of stay, insurance status,
      hospital and physician charges, and ultimate outcome. RESULTS: Of the 84 men and
      31 women, 66 were perpetrators, either as the driver (34) or passenger (32) of a
      stolen vehicle. Perpetrators were significantly younger and more likely to be
      male than victims. The overall mortality was 11%. An additional nine fatalities
      occurred at the scene of a MVC linked to a patient in this study. A high rate of
      speed and the presence of police pursuit seemed to be related to the severity of
      the crashes. The mean charges (hospital and physician) were over $34,000 per
      patient, and the aggregate charges for this cohort were greater than $3.6
      million. Fifty-four percent of patients were uninsured. CONCLUSION: Injuries
      involving stolen cars are common in areas in which the activity has a high
      prevalence and can compose a significant percentage of a trauma center's MVC
      population. These data run contrary to the popular belief that auto theft is
      merely a crime against property, because the injuries sustained as a result of
      this criminal activity tended to be severe and were associated with a high
      fatality rate. Restricting police pursuit to only those instances in which other
      felonious activity is suspected may decrease the number of stolen car MVC.
      Additionally, the total amount of uncompensated care that these patients receive
      places another financial burden on limited health care and trauma center
      resources, which ultimately effects all other citizens.

PMID- 9783622
TI  - Effectiveness of helicopter versus ground ambulance services for interfacility
      transport.
AB  - BACKGROUND: Helicopters provide rapid interfacility transport, but the effect on
      patients is largely unknown. METHODS: Patients requested to be transported
      between facilities by helicopter were followed prospectively to determine
      survival, disability, health status, and health care utilization. A total of
      1,234 patients were transported by the primary aeromedical company; 153 patients
      were transported by ground and 25 patients were transported by other aeromedical
      services because of weather or unavailability of aircraft. RESULTS: There were no
      differences at 30 days for survivors in disability, health status, or health care
      utilization. Nineteen percent of helicopter-transported patients died compared
      with 15% of those transported by ground (p=0.21). CONCLUSION: The patients
      transported by helicopter did not have improved outcomes compared with patients
      transported by ground. These data argue against a large advantage of helicopters
      for interfacility transport. A randomized trial is needed to address these issues
      conclusively.

PMID- 9783623
TI  - The ICD-9-based illness severity score: a new model that outperforms both DRG and
      APR-DRG as predictors of survival and resource utilization.
AB  - OBJECTIVE: This project is designed to develop and validate a predictive model
      that is a useful benchmarking and quality of care assessment tool based on
      International Classification of Diseases, Ninth Revision (ICD-9), diagnoses and
      procedures. This model, the ICD-9-Based Illness Severity Score (ICISS), was
      developed from the Agency for Health Care Policy Research's Health Care
      Utilization Project database and is used to predict hospital survival, hospital
      length of stay, and hospital charges of injured patients admitted to University
      of North Carolina Hospitals. The study also compared the outcome predictions of
      ICISS with those of the long-established diagnosis-related groups (DRG) and the
      3M product APR-DRG systems. METHODS: We performed a retrospective study of 9,483
      trauma patients at University of North Carolina Hospitals. A model was developed
      to predict survival, length of stay, and hospital charges. The accuracy of the
      model of survival was assessed using the area under the receiver-operating
      characteristics curve; the adjusted R2 statistic was used to judge the proportion
      of variation described by the models of length of stay and hospital charges.
      RESULTS: ICISS proved to be superior to both DRG and APR-DRG in predicting
      survival of trauma patients: the area under the receiver-operating
      characteristics curve for prediction of hospital survival was 0.957 for ICISS,
      0.707 for DRG, and 0.808 for APR-DRG. ICISS also outperformed DRG and APR-DRG in
      predicting hospital length of stay and hospital charges: the adjusted R2 for the
      ICISS length of stay model was 0.57, compared with the DRG length of stay model
      with adjusted R2 of 0.31 and the APR-DRG length of stay model with adjusted R2 of
      0.35. The adjusted R2 for the ICISS hospital charges model was 0.67, compared
      with the DRG and APR-DRG hospital charges model R2 of 0.46 and 0.51, respectively
      (p < 0.001 in all cases). CONCLUSION: This study demonstrates that an ICD-9-based
      predictive model (ICISS) can markedly outperform both DRG and APR-DRG as a
      predictor of survival, hospital length of stay, and hospital charges.

PMID- 9783624
TI  - Outcome and cost of trauma among the elderly: a real-life model of a single-payer
      reimbursement system.
AB  - BACKGROUND: As our population ages, the number of elderly trauma patients (age >
      or = 65 years) increases. Studies have demonstrated increased mortality and cost
      for a given injury severity in the elderly compared with younger patients. The
      financial viability of trauma centers in the United States has been an area of
      concern for many years. As reimbursement diminishes for privately insured
      patients, the ability to finance the care of the indigent is jeopardized.
      Medicare, the single-payer insurance plan for the elderly, reimburses at a lower
      rate than standard private insurance carriers. We examined the differences in
      outcome and cost between the elderly and younger patients and the financial
      burden imposed by care for elderly trauma. Our hypothesis was that elderly trauma
      patients would have poorer outcomes, higher cost, and generate greater financial
      losses than younger patients. METHODS: All patients admitted to the University of
      Virginia Trauma Service from July 1, 1994, to July 1, 1997 were included. Trauma
      registry and patients records were examined. Patients with incomplete financial
      data (cost, reimbursement, and payer source) were excluded. Patients were grouped
      by age (18-64 and > or =65 years), Injury Severity Score, and payer source.
      RESULTS: One thousand one hundred twenty-seven patients met the entry criteria.
      One hundred forty patients had incomplete financial or patient data and were
      excluded. Nine hundred eighty-seven patients were included in the study, of which
      159 were elderly and 828 were 18 to 64 years of age. Injury Severity Scores were
      significantly higher in the elderly group. Only 2% of elderly patients were
      uninsured (76% were insured by Medicare), whereas 25% of younger patients were
      uninsured. Medicare reimbursement rates actually exceeded those of all other
      carriers (114% of costs). Elderly patients had a higher mortality rate, but the z
      score did not reach significance. The W score, however, indicated that there were
      more unexpected, negative outcomes among elderly patients. As injury severity
      increased, profit per case increased in the elderly and decreased in the younger
      group. CONCLUSION: Despite higher injury severity and lower survival probability
      for the elderly, the length of hospital and intensive care unit stays, as well as
      the percentage of admissions to the intensive care unit, were similar. The per
      capita cost of hospital care for the elderly was lower than for younger patients,
      whereas reimbursement was higher, primarily because 98% of elderly patients were
      insured. Medicare, the single-payer insurance plan for the elderly, adequately
      reimburses for elderly trauma care. This implies that universal insurance
      coverage for all trauma patients would be desirable, even if reimbursement rates
      decreased significantly. The increased mortality in the elderly requires
      continued study and diligence.

PMID- 9783625
TI  - Differences in mortality between elderly and younger adult trauma patients:
      geriatric status increases risk of delayed death.
AB  - BACKGROUND: Elderly patients suffer higher mortality rates after trauma than
      younger patients. This increased mortality is attributable to age, preexisting
      disease, and complications as well as injury severity. METHODS: Records from
      5,139 adult patients from a Level I trauma center were retrospectively reviewed.
      Injury Severity Score (ISS), Revised Trauma Score (RTS), early mortality (<24
      hours), and late mortality (>24 hours) were determined for elderly (> or =65
      years) and younger (16-64 years) patients. Preexisting diseases and complications
      were identified by International Classification of Diseases, Ninth Revision,
      Clinical Modification diagnosis coding. RESULTS: Mortality in elderly patients
      was twice that in younger patients despite equivalent injury severity (p <
      0.001), and elderly patients were more likely to suffer later death than younger
      patients (p < 0.005). The prevalence of preexisting disease was greater in the
      elderly, as was the incidence of complications. Using logistic regression, ISS,
      RTS, preexisting cardiovascular or liver disease, the development of cardiac,
      renal, or infectious complications, and geriatric status were all independently
      predictive of late mortality (p < 0.05). CONCLUSION: Elderly trauma patients more
      frequently suffer late mortality than younger patients because of the combination
      of injury and increased preexisting disease and complications after injury.
      Aggressive treatment of the elderly trauma patient is warranted; however, in the
      face of significant preexisting disease or complications, survival is less
      likely. Predictive models of survival can be developed, taking into account
      preexisting disease and complications as well as admission parameters such as
      age, ISS, and RTS, and specific risk of mortality quantitated.

PMID- 9783627
TI  - A temporal correlation of pain and endotoxin levels in sickle cell disease.

PMID- 9783626
TI  - Ethylene glycol intoxication presenting as a metabolic acidosis associated with a
      motor vehicle crash: case report.

PMID- 9783628
TI  - Hydrostatic rectal injury of a jet ski passenger: case report and discussion.

PMID- 9783629
TI  - Traumatic thoracobiliary fistula: report of a case successfully managed
      conservatively, with an overview of current diagnostic and therapeutic options.
AB  - Thoracobiliary fistula is a rare complication of hepatic trauma that may present
      a diagnostic and therapeutic challenge. We report a case of a thoracobiliary
      fistula complicating thoracoabdominal trauma. Although numerous imaging
      modalities are able to detect the condition, optimal imaging is achieved with
      endoscopic retrograde cholangiography, which provides anatomic delineation and
      has the therapeutic potential of a sphincterotomy. Conservative therapy consists
      of a safe temporizing measure during the workup and may, on occasion, be the only
      therapy that is necessary provided that controlled drainage of the fistula is
      achieved. The current recommendation would be the exhaustion of nonoperative
      therapeutic modalities before resorting to surgical intervention.

PMID- 9783630
TI  - Transdiaphragmatic intercostal hernia resulting from blunt trauma: case report.

PMID- 9783631
TI  - Median nerve palsy after humeral shaft fracture: case report.

PMID- 9783632
TI  - Fracture dislocation of the proximal row of the wrist: case report.

PMID- 9783633
TI  - Ruptured lumbar artery pseudoaneurysm: a diagnostic dilemma in retroperitoneal
      hemorrhage after abdominal trauma.

PMID- 9783634
TI  - Delayed atrial rupture after blunt chest trauma.

PMID- 9783636
TI  - Hepatic and oral trauma in an infant related to improper use of an infant car
      seat.

PMID- 9783635
TI  - The spectrum of lap belt injuries sustained by two cousins in the same motor
      vehicle crash.

PMID- 9783637
TI  - Ultrasound in blunt abdominal trauma.

PMID- 9783638
TI  - Prone positioning in acute lung injury.
AB  - More than 20 years ago, critical care workers first observed that oxygenation
      improved when patients with acute respiratory distress syndrome were ventilated
      in the prone position. In recent reports, on turning prone, from 50 to 100% of
      patients improve oxygenation to a degree sufficient to allow a reduction in the
      level of positive end-expiratory pressure or fraction of inspired oxygen. It
      appears that vascular conductance in lung regions previously in the dorsal
      position is augmented by an increase in air space volume, with the effect that
      prone position ventilation will reduce shunt and improve ventilation-perfusion
      mismatch. Factors determining which patients will respond have not yet been
      elucidated. Although many questions regarding the role of prone ventilation are
      unanswered, of greatest importance is whether this technique reduces morbidity
      and mortality of patients with acute respiratory failure. Only carefully
      conducted, randomized trials can answer this question.

PMID- 9783639
TI  - Vaginal evisceration resulting from a water-slide injury.

PMID- 9783640
TI  - Rarity of traumatic abdominal wall hernias.

PMID- 9783641
TI  - Posttraumatic pulmonary pseudocyst.

PMID- 9783642
TI  - Shock waves in vascular diseases: an in-vitro study.
AB  - Three human aortic specimens were used for this in-vitro study on the effects of
      shock waves on the arterial wall. Specimen one was from a normal (for age)
      healthy aorta. The full abdominal length was used (including mesenteric and renal
      arteries and the aortoiliac bifurcation), divided into six pieces (3 cm). The
      pieces were placed and fixed into degassed water. Shock waves (SW) were focused
      onto the aortic wall by means of a B-mode ultrasound imager. An SW generator
      (Minilith SL1, Storz Medical AG, Kreuzlingen, Switzerland) was used for setting
      of energy flux density between 0.03 and 0.5 mJ/mm2. The six aortic pieces
      (excluding piece 1, placed in water and left untreated as control) were treated
      with SW at increasing energy levels. A second aortic specimen of a man with
      arteriosclerotic plaques was also used and the experiment repeated at energy
      levels 1, 5, and 8. Another specimen of normal thoracic aorta was exposed at
      energy levels 1 and 8 only. Energy levels delivered onto the aortic walls were
      selected from theoretically destructive levels to minimal levels known not to
      alter vascular tissues. High-resolution ultrasounds of the aortic segments were
      performed with a 10 MHz high-resolution, broad-band (ATL 3000, USA) probe in
      water before and after SW application to detect structural changes in the wall
      after SW. Histology was performed with a standard hematoxylin-eosin staining.
      RESULTS: The aortic pieces did not show macroscopic damages at visual
      examination, and at the ultrasound examination no visible changes were observed
      even at higher levels of SW energy. Also no effects were seen by histology. In
      conclusion, no damaging effects were observed, visually, by ultrasound, or by
      histology. At these energy levels SW appear to be safe and do not produce any
      damage to the aortic wall. Therefore, SW could be considered a safe, nondamaging
      procedure for potential treatment (ie, thrombolysis) in which vessel walls could
      be involved. Theoretically it is possible that functional changes could be
      observed in vivo including cell permeability modifications and other alterations
      (including changes in the potential of the cells in SW fields to modify
      themselves and to divide). At the energy levels described in this study SW could,
      theoretically be, safely used for vascular applications (ie, treating venous and
      arterial thrombi or in arterial plaques modification) without altering major,
      structural, arterial wall characteristics. Lesions or alterations that have a
      different density from the normal wall (thrombi or plaques) could be differently
      sensitive to the same dosage of SW. These differences in acoustic impedance
      characteristics could be used for potential treatments with SW without damaging
      the arterial wall.

PMID- 9783643
TI  - Risk factors for development of acute renal failure (ARF) requiring dialysis in
      patients undergoing cardiac surgery.
AB  - Acute renal failure (ARF) is one of the major complications after cardiopulmonary
      bypass for open heart operations. The present study was undertaken to identify
      the risk factors for the development of ARF following cardiopulmonary bypass
      (CPB). Four hundred and forty-seven consecutive patients who underwent open heart
      procedures from July 1994 to June 1995 were analyzed retrospectively. Their mean
      age was 55.6 +/- 14.2 (SD) years (range, 18 to 80). Dialysis was instituted
      whenever a patient exhibited inadequate urine output (<0.5 mL/kg/hr) for 2 to 3
      hours despite correction of hemodynamic status and diuretic therapy, especially
      if fluid overload, hyperkalemia, or metabolic acidosis were also present. Twenty
      variables were analyzed by univariate analysis; these included nine preoperative
      variables--age, sex, hypertension, atherosclerosis, diabetes mellitus, left
      ventricular end-diastolic dimension (LVEDD) >5 cm, preoperative congestive heart
      failure, renal insufficiency (serum creatinine > or =130 micromol/L on two
      occasions), and sepsis--10 intraoperative variables--duration of CPB, redo
      procedures, emergency surgery, use of intraaortic balloon pump (IABP) in
      operating room, use of gentamicin, use of ceftriaxone, use of
      sulbactam/ampicillin, requirement of deep hypothermic circulatory arrest,
      duration of low mean perfusion pressure (mean pressure <50 mmHg for more than 30
      minutes), operation on multiple valves--and one postoperative variable-
      significant hypotension (systolic blood pressure less than 90 mmHg for more than
      1 hour). Significant variables or the variables having a trend (p<0.1) to be
      associated with ARF were included in stepwise multiple logistic regression
      analyses. Three regression analyses were performed separately. The incidence of
      ARF requiring dialysis in the study period was 15.0%. Significant risk factors
      for whole group of patients (regression I) were preoperative renal insufficiency
      (p<0.0001), postoperative hypotension (p<0.0001), cardiopulmonary bypass time
      more than 140 min (p<0.005), preoperative congestive heart failure (p<0.01), and
      history of diabetes mellitus (p<0.01). The risk factors in the valve group of
      patients (regression II) were preoperative renal insufficiency (p<0.0001) and
      postoperative hypotension (p<0.05). Risk factors in the CABG patients (regression
      III) were postoperative hypotension (p=0.0001), CPB time more than 140 min
      (p<0.05), preoperative renal insufficiency (p<0.05), and age (p<0.05). The
      authors conclude that preoperative renal insufficiency and postoperative
      hypotension are the most important independent risk factors for ARF in
      postcardiac surgical patients. In addition, CPB time greater than 140 minutes and
      old age are also independent risk factors for ARF in CABG patients. CPB time more
      than 140 minutes, history of diabetes mellitus, and preoperative congestive heart
      failure are independent risk factors for development of ARF in our total group of
      patients. These findings may have important clinical implications in the
      prevention of ARF in postcardiac surgical patients.

PMID- 9783644
TI  - Present status of HMG reductase inhibitors in treatment of dyslipidemia.
AB  - HMG reductase inhibitors have significant desirable effects on patients with
      dyslipidemia. Multiple factors are involved in these desirable effects. Other
      factors that might play a role in the risk of coronary artery disease are
      fibrinogen concentration, homocysteine, Lp (a), small dense LDL, insulin
      resistance, and infection with chlamydia. High-dose reductase inhibitors may be
      indicated in select patients. The ideal end point may be 150 mg/dL for adults.

PMID- 9783645
TI  - Plasma soluble P-selectin in acute myocardial infarction: effects of coronary
      recanalization therapy.
AB  - P-selectin is translocated from platelets and endothelial cells to initiate the
      first step in a sequence of events leading to the adherence of leukocytes,
      possibly inducing reperfusion injury and the no-reflow phenomenon in acute
      myocardial infarction (AMI). This study was undertaken to investigate plasma P
      selectin in AMI patients undergoing coronary recanalization therapy. A total of
      40 patients were studied: 20 patients with AMI who underwent coronary
      recanalization by direct percutaneous transluminal coronary angioplasty (PTCA),
      10 patients with AMI who underwent thrombolytic therapy by tissue-type
      plasminogen activator (TPA), and 10 patients with stable angina pectoris who
      underwent elective PTCA. Blood samples were obtained from systemic arteries
      before and immediately after PTCA or thrombolytic therapy. Plasma-soluble P
      selectin was measured by enzyme immunoassay. Plasma P-selectin was significantly
      higher in AMI than in stable angina pectoris (176.6 +/- 12.9 ng/mL vs 91.4 +/-
      9.5 ng/mL, p<0.001). Plasma P-selectin did not change significantly as a result
      of elective PTCA in patients with stable angina (from 91.4 +/- 9.5 ng/mL to 87.9
      +/- 7.9 ng/mL). Plasma P-selectin was decreased by direct PTCA in all of the 20
      patients with AMI (from 176.2 +/- 17.7 ng/mL to 141.7 +/- 12.6 ng/mL; p<0.001,
      paired t-test), whereas it was increased by thrombolysis using TPA in nine of the
      10 AMI patients (from 177.4 +/- 17.2 ng/mL to 248.8 +/- 17.3 ng/mL, p<0.005).
      Increased P-selectin activity in AMI appeared to be attenuated by direct PTCA,
      but augmented by thrombolysis, possibly due to direct stimulatory effects of TPA
      on P-selectin expression. This may lead to less favorable results in salvaging
      the ischemic myocardium by thrombolytic than mechanical coronary recanalization
      therapy in AMI.

PMID- 9783646
TI  - Enhanced insulin response to oral glucose load in patients with angina pectoris
      associated with ST segment elevation in the absence of epicardial coronary
      arterial obstruction.
AB  - The authors treated 10 patients with microvascular angina (MVA) manifesting
      angina pectoris, ST segment elevation suggestive of transmural myocardial
      ischemia, and no epicardial arterial obstruction. Since such patients frequently
      showed abnormal responses to oral glucose loading, the authors investigated the
      glucose and insulin responses to glucose loading in 10 MVA patients, 25 patients
      with vasospastic angina (VAP), 25 patients with effort angina (EAP), and 25
      control subjects. Insulinogenic index, peripheral insulin activity [= 10(4)/(peak
      glucose x insulin at glucose peak)], glucose area, and insulin area were
      calculated. The MVA group included two patients with impaired glucose tolerance
      and two newly diagnosed diabetic patients. These proportions were similar to
      those in the VAP and EAP groups. Glucose levels at 30 to 180 min and insulin
      levels at 90 to 120 min in the MVA group were higher than in the control group.
      Peak glucose, glucose area, peak insulin, and insulin area were higher in the MVA
      group than in the control group (p<0.01). Those in the VAP and EAP groups were
      also higher. Insulin/glucose ratio at 120 min was higher, peripheral insulin
      activity, lower, in the disease groups than in the control group (p<0.05). The
      MVA patients showed a hyperglycemic and hyperinsulinemic response to oral glucose
      loading, as did the patients with EAP and VAP. Enhanced insulin response to oral
      glucose loading may also contribute to the pathogenesis of MVA.

PMID- 9783647
TI  - Decreased prevalence of symptomatic atherosclerosis in arthritis patients on long
      term aspirin therapy.
AB  - To determine the effect of long-term aspirin therapy on the prevalence of
      symptomatic atherosclerosis, autopsy results from 44 arthritis patients taking
      aspirin were compared with a cohort from the general autopsy population. No
      decrease in the prevalence of symptomatic atherosclerosis was noted in patients
      with less than 8 years of arthritis, compared with controls. In contrast, the
      prevalence of symptomatic atherosclerosis was significantly decreased in
      arthritis patients with 8 or more years of arthritis and aspirin use. In these
      subjects, the prevalence of symptomatic atherosclerosis was inversely related to
      duration of arthritis. The inverse relationship between prevalence of symptomatic
      atherosclerosis and duration of aspirin therapy, as well as the decrease in all
      forms of symptomatic atherosclerosis, raise the possibility that this decrease is
      due to primary prevention of atherosclerosis.

PMID- 9783648
TI  - Fast rotating atherectomy catheter tip inhibits platelet aggregation and ATP
      release: a study using platelet-rich plasma.
AB  - The interaction of atherectomy devices with the arterial wall is the focus of
      many studies, but their effect on the surrounding blood is largely unknown. This
      is a detailed investigation on the effects of a rotational atherectomy device
      with a fast rotating tip on platelet structure and function. Platelet-rich plasma
      (PRP) was obtained from six volunteers, divided into 5 mL samples, and subjected
      to the atherectomy tip rotating at 20, 40, or 80 thousand rpm for 30 or 60
      seconds. Platelet aggregation to collagen or adenosine diphosphate (ADP) was
      obtained in all samples by means of a dual-chamber optical aggregometer. The fast
      rotating catheter tip caused marked inhibition of platelet aggregation to both
      collagen and ADP. The maximum extent of aggregation was reduced from 85% +/-2.8
      in control to 46% +/-4.8 with collagen (p<0.01) and from 86.1% +/-6.9 to 25.1% +/
      4.3 with ADP (p<0.01). The rate of aggregation (measured at 4 minutes) dropped
      from 81.3% +/-2.7 to 40% +/-4.5 and from 73.9% +/-8.5 to 12.5% +/-2.6 (p<0.005)
      with collagen and ADP, respectively. These effects were related to rotating speed
      and duration of exposure. ATP release in response to collagen fell from 2.63 +/
      0.13 nMol in control to 0.7 +/-0.1 nMol, p<0.001 after exposure to the rotating
      tip. There was no significant change in platelet count, nor was there formation
      of platelet aggregates (platelet aggregate ratio remained unchanged) to account
      for these phenomena. Furthermore, transmission electron microscopy showed no
      significant platelet disruption or release of granules, and little signs of
      activation were seen even after addition of collagen. This is the first study to
      demonstrate that exposure to a fast rotating catheter tip inhibits in vitro
      platelet aggregation and ATP release. There were no apparent loss of integrity of
      platelet structure, release of granules, or formation of platelet aggregates.
      This phenomenon and its clinical implication justify further investigation.

PMID- 9783649
TI  - Intermittent claudication and risk of cardiovascular events.
AB  - To determine the natural history of intermittent claudication, 110 patients were
      followed up for a mean period of 24.4 +/- 1.2 months. Four patients died during
      the follow-up. Of the survivors, 24 experienced a nonfatal cardiovascular event,
      myocardial infarction being the most frequent. Cumulative cardiovascular
      morbidity was 29% at 3 years. Cox proportional-hazards analysis showed initial
      ankle-brachial pressure index (ABPI) as a significant predictor for nonfatal
      cardiovascular events (p<0.002). With an initial ABPI >0.70, cardiovascular
      morbidity rate was 12% compared with 33% for those with initial ABPI ranging from
      0.70 to 0.50, and 60% for those with ABPI <0.50 (p<0.005). Critical limb ischemia
      occurred in only four patients, amputation was required in two, and arterial
      reconstruction in five. Of the 85 patients who participated in the treadmill
      test, maximum walking capacity worsened in 26% and improved in 27%. This study
      elucidates the neglected area of cardiovascular morbidity in intermittent
      claudication. It has shown that ABPI identifies a subgroup of patients for whom
      the risk of cardiovascular events is especially pronounced. On the other hand,
      based on objective evaluation of the patient status, the relatively benign
      prognosis for the claudicant limb has been confirmed.

PMID- 9783651
TI  - Implantation of a mechanical valve within the orifice of a mitral bioprosthesis
      in a case with severely calcified left atrium--a case report.
AB  - The case of a 61-year-old woman with deterioration of mitral bioprosthesis and
      severe left atrial calcification is presented. Although the implantation of a
      mechanical valve within the orifice of a mitral bioprosthesis was tried, we found
      a major pitfall in this method was exact orifice matching.

PMID- 9783650
TI  - Clinical characteristics in Japanese patients with coexistent hypertrophic
      cardiomyopathy and coronary vasospasm.
AB  - There are only a few reports concerning coexistent hypertrophic cardiomyopathy
      (HCM) and vasospastic angina. Clinical characteristics in patients with both
      diseases have not been clarified yet. This study was designed to elucidate the
      relationship between chest pain and coronary vasospasm in HCM patients and to
      delineate clinical characteristics in patients with both HCM and coronary
      vasospasm. First, 36 patients with HCM underwent acetylcholine provocation test
      for coronary vasospasm and were divided into two groups on the basis of presence
      or absence of coronary vasospasm. Next, the following risk factors for coronary
      artery disease were compared between the two groups: hypertension, smoking,
      hyperlipidemia, diabetes mellitus, and hyperuricemia. Coronary vasospasm was
      induced in 10 (28%) of 36 patients with HCM. There were no significant
      differences in age and male gender between the two groups. Smoking was more
      prominent in HCM patients with than without coronary vasospasm (80% vs 35%,
      p<0.05), but there were no differences in the prevalence of other risk factors
      between the two groups. In conclusion, coronary vasospasm appears to play a
      significant role in the etiology of myocardial ischemia in Japanese patients with
      HCM, and smoking might be a major risk factor for coexistence of HCM and coronary
      vasospasm.

PMID- 9783652
TI  - Massive bilateral pulmonary embolism in a patient with subsequent occurrence of
      severe mitral regurgitation due to ruptured chordae tendineae--a case report.
AB  - This report concerns an apparently healthy woman who presented simultaneously
      with acute massive bilateral pulmonary embolism and mitral regurgitation,
      subsequently, a month later, resulting in pulmonary edema secondary to chordae
      rupture of the mitral valve. The authors believe that massive pulmonary embolism
      predisposed to chordal rupture in this case. It is suggested that increased
      awareness of ruptured chordae tendineae as a cause of mitral regurgitation and
      the prompt use of transesophageal echocardiography will facilitate the early
      recognition of this potentially fatal, but treatable, cause of mitral
      regurgitation in patients with pulmonary embolism.

PMID- 9783653
TI  - Acquired atrial septal defect as a complication of endocarditis--a case report.
AB  - Bacterial endocarditis predominantly involves cardiac valves and is associated
      with many potential complications. Valvular dysfunction resulting from disruption
      of the structural integrity of valves are not infrequent. This report illustrates
      a rare case of endocarditis involving the interatrial septum which subsequently
      produced destruction of the structure resulting in an acquired atrial septal
      defect.

PMID- 9783654
TI  - TRAUT: a Rorschach index for screening thought disorder. Tripartite
      Classification of Autisms.
AB  - TRAUT, a new approach to the recognition and classification of perceptions on the
      Rorschach indicative of thought disorder, is based on the rationale that so
      called autisms are really "absurdities" that lead to interpretive contradictions.
      Advantages of TRAUT's logically derived definitions include clarity,
      generalizeability, and teachability. TRAUT categorizes autisms according to
      whether they ignore the blot (HYPO), circumvent the task (HYPER) or rationalize
      counterfactual images by spatial juxtaposition (RELER). Norms and significance
      tests are presented, demonstrating that thought-disordered patients produce
      higher TRAUT scores than nonthought-disordered patients and normal individuals.
      TRAUT categories were also able to differentiate among various types of thought
      disordered patients.

PMID- 9783655
TI  - Development of the gambling attitude scales: preliminary findings.
AB  - Social scientists recognize gambling as a universal phenomenon that occurs in a
      myriad of forms. Although gambling is often a harmless social activity. some
      participants become pathological gamblers. Given the negative consequences
      associated with pathological gambling, it is important to understand attitudes
      toward gambling because they typically represent a readiness to act. One hundred
      and seventy university students completed four gambling attitude scales
      constructed to measure general attitudes and attitudes toward gambling in
      casinos, betting on horse races, and playing the lottery. Results showed the
      scales to be internally consistent and to have short-term temporal stability. The
      most positive attitudes were shown toward playing the lottery and the least
      positive were shown toward betting on horse races. In general, men reported more
      positive attitudes than women. Positive attitudes toward gambling were related to
      a tendency toward risk taking.

PMID- 9783656
TI  - Comorbidity of DSM-IV personality disorders in a nonclinical sample.
AB  - The issue of comorbidity within the Axis II personality disorders was explored
      using a large sample of university students who were administered the Coolidge
      Axis II Inventory (CATI). Comorbidity patterns with this normal sample were
      compared with recent clinical data reported by several other researchers. The
      results confirm the high degree of comorbidity within Axis II and the similarity
      in the comorbidity patterns with clinical and nonclinical samples. With the CATI,
      a 30.4% comorbidity rate was obtained for Histrionic and Narcissistic Personality
      disorders (Pd). The paranoid, passive-aggressive and borderline personality
      disorder traits were comorbid with several other Pds. For Cluster A, there was
      low comorbidity except for Paranoid Pd and Schizotypal Pd. With Cluster B, the co
      occurrence was moderate to strong. A moderate amount of interrelationship was
      obtained for the Cluster C Pds. The DSM-IV clusters were also strongly
      interrelated. An additional finding was the similarity between self-report and
      structured interview methodology in obtained personality disorder comorbidity.

PMID- 9783657
TI  - Research contributions of counseling psychologists to neuropsychology.
AB  - Research productivity of counseling psychologists with credentials in clinical
      neuropsychology were examined. Eighteen were ABPP/ABCN Diplomates. Division 40
      Fellows, or both. They published an average of 3.06 (SD= 4.82; range = 0 to 20)
      neuropsychologically relevant, first-authored articles over the past 5 years.
      When counseling psychologists were compared to a random sample of ABPP/ABCN
      diplomates with doctoral degrees in other areas of psychology, no reliable
      differences emerged between the groups in age, research productivity, or number
      of years between graduation and receipt of the ABPP/ABCN diploma. Research
      contributions of neuropsychologists with degrees in counseling psychology are
      comparable to those of ABPP/ABCN diplomates who were trained in other areas of
      psychology (e.g., clinical, developmental, and physiological).

PMID- 9783658
TI  - Couples critical incidents checklist: a construct validity study.
AB  - This study examined the initial construct validity of the Couples Critical
      Incidents Checklist (CCICL; Piedmont & Piedmont, 1996). One hundred nine
      heterosexual married couples completed the CCICL to assess levels of marital
      satisfaction and the NEO PI-R to assess personality factors. As hypothesized, the
      rater-reports (R) and the self-ratings (S) of each of the five personality
      dimensions correlated systematically with the kinds of marital issues identified
      on each of the five sections of the CCICL. For instance, the Flexibility scale of
      the CCICL captured issues related to the dimension Openness (O) or the
      Cooperativeness scale of the CCICL assessed issues related to Agreeableness (A).
      Second, it was hypothesized that specific behavioral problems experienced by the
      spouses within the marital relationship would significantly correlate with the
      level of marital satisfaction. Overall, the analyses of the data of both the men
      and the women suggested that the contributing cause of marital dissatisfaction
      was not a specific behavioral problem experienced with the spouse, but rather the
      aggregate of all behavioral problems experienced with the spouse.

PMID- 9783659
TI  - Establishing the psychometric properties of the DSM-III-R personality disorders:
      implications for DSM-V.
AB  - In this study, symptom (item) level data were used to perform a psychometric
      analysis of the DSM-III-R personality disorders (PDs). Determined for each PD
      criteria set were convergent validity, discriminant validity, and internal
      consistency. The results indicated that the majority of the PD criteria sets (6
      of the 11 ) possessed adequate convergent validity, although discriminant
      validity was problematic for most of these disorders. Internal consistency was
      also weak for the PD criteria sets, with only 3 of the 11 exceeding a minimum
      cutoff score of .70. The present study employed a methodology modeled after the
      one reported by Morey (1988a), and the results of the two studies were highly
      similar. Consistent findings across the two data sets can be taken to reflect the
      actual psychometric properties of the DSM-III-R PDs. The success of our
      replication demonstrates the potential that large-scale psychometric
      investigations hold for aiding the development and refinement of the DSM PDs.

PMID- 9783660
TI  - Rorschach indicators of dissociative identity disorders: clinical utility and
      theoretical implications.
AB  - The purpose of the present study was to replicate Rorschach signs of Multiple
      Personality Disorder (MPD) using DSM-IV criteria of Dissociative Identity
      Disorder (DID). Women admitted to either an inpatient dissociative disorder's
      unit (n = 27) or a general psychiatric unit (n = 72) were given the Rorschach,
      which was scored for the Labott, Barach, and Wagner Rorschach markers of MPD.
      Results indicated that Rorschach signs of the three different systems were
      significantly better than chance at classifying patients as DID or as non-DID.
      The Labott system, which performed the best, was able to accurately classify 92%
      of the sample. These results argue for the validity of the DID diagnosis. The
      Rorschach signs operate independent of external bias, yet correspond to the
      diagnoses obtained through psychiatric evaluation in an inpatient setting. The
      fact that two relatively rare sets of signs (DID and Rorschach) converge in the
      same small sector of the psychiatric population represents evidence of linkage
      that is clinically meaningful and not explainable on the basis of artificial
      creation.

PMID- 9783661
TI  - Intellectual evaluations of adolescents via human figure drawings: an empirical
      comparison of two methods.
AB  - The human figure drawings of 200 adolescent boys were collected at a residential
      treatment center in a midsized, midwestern city. The drawings were scored for
      cognitive ability according to the systems of Buck (1966) and Goodenough and
      Harris (1963). Both scoring systems showed acceptable interrater reliability and
      both were positively and significantly related to IQ scores on the Wechsler
      Intelligence Scale for Children-Revised. Buck's system, however, had less of a
      tendency to underestimate IQ scores. Buck's system may therefore hold greater
      promise for the intellectual assessment of adolescents with human figure
      drawings.

PMID- 9783662
TI  - Development of the Marital Self-disclosure Questionnaire (MSDQ).
AB  - This research describes the development of the Marital Self-Disclosure
      Questionnaire (MSDQ), a brief, self-report measure of the quantity and quality of
      marital self-disclosure. Consisting of 40 true-false items, the MSDQ provides a
      global index of marital self-disclosure as well as assesses four facets of self
      disclosure between spouses: Relationship, Sex, Money, and Imbalance. Results
      indicate that the MSDQ scales are reliable, and preliminary data suggest that the
      MSDQ may have validity for distinguishing among groups hypothesized to differ in
      terms of marital distress and self-disclosure. Further evaluation of the MSDQ for
      its clinical and research utility appears to be warranted.

PMID- 9783663
TI  - Personality patterns of anxiety during occupational deep dives with long-term
      confinement in hyperbaric chamber.
AB  - Extreme environments are generally thought to be stressful situations.
      Occupational deep diving inflicts periods of long-term confinement in hyperbaric
      chambers and high-pressure exposure on divers. Such extreme environmental
      conditions have been demonstrated to produce acute responses of anxiety in
      individual divers. Although these studies have mentioned personality as a factor
      explaining why some divers reported an increase in ratings of anxiety, the role
      of personality traits still remains unclear. The present study examines the
      possible role of personality traits in the development of diving anxiety. Results
      confirm that diving anxiety remains at the individual level and relatively
      transient and suggest that personality factors, such as low self-control and
      emotional instability, that reflect an incapacity to control and express tension
      in an appropriate manner would play a crucial role in the occurrence of diving
      anxiety.

PMID- 9783664
TI  - Cognitive and behavioral correlates of depression in learning-disabled and
      nonlearning-disabled adult students.
AB  - Cognitive and behavioral correlates of depression were examined in 33 learning
      disabled (LD) and 99 nonlearning-disabled (NLD) adult students. Self-reported
      depressive symptomatology was significantly correlated with dysfunctional
      cognitions and reinforcement level in LD students. LD students reported engaging
      in significantly more unpleasant activities and experiencing significantly less
      pleasure than NLD students. There was a nonsignificant trend for LD students to
      report more depression than NLD students. These results are discussed in the
      context of cognitive and behavioral theories of depression.

PMID- 9783665
TI  - Internal consistency reliability of the Personality Assessment Inventory with
      psychiatric inpatients.
AB  - Internal consistency reliability (Cronbach's alpha) estimates and standard errors
      of measurement were determined for the Personality Assessment Inventory (PAI;
      Morey, 1991) with a group of psychiatric inpatients (N = 111). Full-scale
      reliabilities were large and acceptable, averaging .82. Subscale reliabilities
      were lower, averaging .66. Reliability estimates for full scales and subscales
      were comparable to those reported for the clinical portion of the PAI
      standardization group. Of the 20 full scales examined, only 2 (Somatization and
      Paranoia) had reliabilities (.85 and .80, respectively) that were significantly
      lower than comparable values reported for the standardization group. Despite
      statistically significant differences, these values were still considered large
      and acceptable.

PMID- 9783666
TI  - Getting the right kind of support: functional differences in the types of social
      support on depression for Chinese adolescents.
AB  - The present study adopted a prospective design to explore relationships among
      various types of social support and depression. Four types of social support,
      namely network support, instrumental enacted support, socio-emotional enacted
      support, and perceived support, were assessed in a sample of Chinese adolescents.
      Results revealed that perceived support was related to a reduction of subsequent
      depression for both male and female adolescents. In addition, instrumental
      enacted support was a significant predictor of subsequent depression for male
      adolescents, whereas socioemotional enacted support was a significant predictor
      of subsequent depression for female adolescents. Functional differences in the
      types of social support for Chinese male and female adolescents, as well as
      implications for clinical intervention, are discussed.

PMID- 9783667
TI  - Research on chronic, low-level exposure to formaldehyde: implications for
      neuropsychological assessment.
AB  - Findings from empirical research serve as the foundation for neuropsychological
      assessment of individuals suspected of exposure to formaldehyde. Insofar as
      conclusions regarding causal relationships between exposure and
      neuropsychological deficits are based on research methodologies that are
      reliable, findings can be informative. Unfortunately, existing research is not
      rooted in sound methodology and findings may mislead rather than enlighten
      clinicians. Two prominent shortcomings in formaldehyde research are discussed:
      selection bias in recruitment of research participants and unreliability of
      participant recall for obtaining data on important background variables and
      exposure levels. Selected examples illustrate the influence of these shortcomings
      on research showing a causal relationship between long-term, low-level exposure
      to formaldehyde and chronic neurobehavioral deficiencies. The implications of
      these weaknesses for assessment of individual patients are discussed.

PMID- 9783669
TI  - Accuracy of a portable International Normalization Ratio monitor in outpatients
      receiving long-term oral anticoagulant therapy: comparison with a laboratory
      reference standard using clinically relevant criteria for agreement.
AB  - The accuracy of a new, portable INR monitor (CoaguChek, Boehringer-Mannheim,
      Indianapolis, IN) was evaluated by comparing INR results from the portable
      monitor with results obtained by a laboratory-based method. Dual INR measurements
      (portable monitor, laboratory) were performed in 163 consecutive outpatients
      receiving warfarin. Agreement in dual INR measurements was defined based on
      clinically-relevant expanded and narrow criteria and statistical criteria.
      Agreement in dual INR measurements also was evaluated as a function of increasing
      INR. The proportion of dual INR measurements that satisfied the clinically
      relevant expanded, and narrow agreement criteria was 90%, and 86%, respectively.
      Seventy-nine percent of all dual measurements were within 0.5 INR units. The
      accuracy of the portable monitor was greatest for INR values less than 3.0; above
      this INR level, the portable monitor underestimated laboratory INR values. The
      proportion of dual INR measurements within 0.5 INR units for laboratory INR
      ranges of <2.0, 2.0-3.0, 3.1-4.0, and >4.0 was 98%, 87%, 57%, and 21%,
      respectively. We conclude that the portable INR monitor achieved a clinically
      acceptable level of accuracy when compared to the traditional laboratory method
      and provides a suitable alternative method of monitoring the INR in patients
      receiving warfarin.

PMID- 9783668
TI  - Thrombin generation and activation of the thrombomodulin protein C system in open
      heart surgery depend on the underlying cardiac disease.
AB  - The exposure of blood to foreign surfaces during extracorporeal circulation (ECC)
      leads to an activation of the coagulation system. In arteriosclerotic patients
      thrombin activation is increased and plasma fibrinogen is elevated, while protein
      C levels are reduced. In this study we investigated the influence of different
      cardiac diseases on ECC-induced thrombin generation and activation of the
      thrombomodulin-protein C system. Twenty-four patients undergoing either elective
      coronary artery bypass grafting (CABG) or elective aortic valve replacement (AVR)
      were included in the study. Blood samples were taken at different time intervals
      before, during and after ECC, and in the postoperative period. Plasma
      concentrations of thrombin-antithrombin III-complex (TAT), modified antithrombin
      (ATM), prothrombin fragment F1+2, free protein S, thrombomodulin, and protein C
      antigen were determined by ELISA. Fibrinogen and antithrombin III levels were
      detected by nephelometry. Both groups were comparable with respect to biometric
      and ECC-related data. TAT concentrations were elevated in both groups after
      induction and increased during surgery (p<0.001). As a marker of thrombin
      generation levels of F1+2 were higher in the CABG group during cardiopulmonary
      bypass (p=0.003). In CABG patients ATM peaks were higher during ECC (p=0.0024).
      Significantly higher plasma thrombomodulin concentrations were found in CABG
      patients after induction (p<0.001), while protein S concentrations were higher in
      the AVR group (p=0.002). Protein C levels and antithrombin III concentrations did
      not differ between the groups. Patients undergoing CABG were found to have lower
      protein S levels and increased plasma thrombomodulin concentrations as markers of
      endothelial damage. In these patients contact activation and as a consequence
      thrombin generation takes place at a higher level, indicating a hypercoagulable
      state. Thromboembolic events in the perioperative period may be caused by
      different hemostatic changes in CABG patients.

PMID- 9783670
TI  - Translocation and phosphorylation of cytosolic phospholipase A2 in activated
      platelets.
AB  - The release of arachidonic acid, and its subsequent conversion to thromboxane A2,
      is an important component of platelet activation. The precise mechanism of
      arachidonic acid release is unknown although cytosolic phospholipase A2 (cPLA2)
      has been implicated. In the present study the effects of three agonists, the
      serine protease thrombin, the protein kinase C stimulant PMA and the calcium
      ionophore A23187 have been examined on the translocation and phosphorylation of
      cPLA2 and these have been correlated with arachidonic acid release. Thrombin, but
      neither PMA nor A23187, caused the release of [14C]-arachidonic acid from
      unstirred, prelabeled platelets. Immunoblot analysis was carried out on cytosolic
      and membrane fractions from control and activated platelets using an anti-cPLA2
      antibody. In platelets stimulated by thrombin or A23187, but not by PMA, there
      was a translocation of cPLA2 to the membrane fraction. Immunoprecipitation of
      cPLA2 from [32P]-ortho-phosphate-prelabeled platelets, indicated enhanced
      phosphorylation on serine residues of cPLA2 from thrombin- or PMA-stimulated
      platelets. These results are consistent with two synergistic pathways mediating
      cPLA2 activity. Increased cytosolic calcium causes the translocation of cPLA2 to
      the membrane, and protein kinase either directly, or indirectly, phosphorylates
      the enzyme. Activation of both pathways, as occurs in response to thrombin, is
      required for arachidonic acid liberation.

PMID- 9783671
TI  - Evaluation of a new antigen capture ELISA for detection and characterization of
      platelet alloantibodies.
AB  - The monoclonal antibody-specific immobilization of platelet antigens (MAIPA)
      assay is considered as a possible reference method for the detection of maternal
      alloantibodies when a foetomaternal alloimmunization is suspected. However, this
      method is tedious. In this study, we have compared the MAIPA results of 54
      samples of mothers with (n=34) or without (n=20) alloantibodies with those
      obtained with a new antigen capture ELISA. Using the cutoff of 2.0 given by the
      manufacturer, the new kit had a sensitivity of 88.2% (95% CI 72.6-96.7) and a
      specificity of 100% (95% CI 98.0-100). From a receiver-operating characteristic
      curve analysis, the more appropriate cutoff for a screening assay would be 1.6,
      which gives a sensitivity of 100% (95% CI 89.7-100) with a specificity of 94.0%
      (95% CI 89.4-96.9). In conclusion, this new simple assay appears promising and
      could be used, with the modified cutoff, as a screening assay for the detection
      of platelet alloantibodies.

PMID- 9783672
TI  - Cloning and recombinant expression of mouse coagulation factor X.
AB  - Engineering of recombinant coagulation factor X variants, which can be activated
      by tumor-associated proteinases may lead to the development of new therapeutic
      molecules. However, the evaluation of such variants requires an appropriate
      animal model. Therefore, we isolated the complete coding sequence of mouse
      coagulation factor X from mouse liver cDNA by polymerase chain reaction. The
      deduced amino acid sequence codes for a prepro protein of 481 amino acids
      homologous to factor X sequences from various species. Recombinant mouse factor X
      was expressed in human embryonic kidney cells and secreted into cell culture
      supernatant as zymogen, which could be converted to catalytically active factor
      Xa by Russell's viper venom. Purified recombinant mouse factor X restored
      coagulation in human factor X deficient plasma, demonstrating that mouse factor X
      is able to functionally interact with the human blood coagulation system.
      Recombinant mouse factor X opens the possibility to analyze therapeutically
      useful variants in the mouse system.

PMID- 9783673
TI  - Cloning and characterization of the gene encoding the murine glycoprotein V: the
      conserved thrombin-cleavable protein on platelet surface.
AB  - Glycoprotein V (GPV) is a platelet membrane protein present as a subunit of the
      GPIb/V/IX complex, a major receptor for von Willebrand factor, and is
      specifically cleaved by thrombin. In this study, we have cloned and characterized
      murine GPV gene. The entire coding sequence of murine GPV consisted of 1704
      nucleotides and coded 567 amino acids, which were 70% identical with human GPV.
      Fifteen leucine-rich tandem repeats were present and the consensus sequence of
      the repeats was completely matched with that of human GPV. The thrombin-cleavage
      site was also conserved exactly at the same position. In Northern blot, murine
      GPV mRNA was specifically expressed in murine platelets, bone marrow cells and
      megakaryocytic cell lines. In the survey of other organs, GPV was not expressed
      at all. These results demonstrate that GPV is highly conserved, thrombin
      cleavable protein beyond the species, and is a specific protein in the platelet
      megakaryocyte lineage.

PMID- 9783674
TI  - Tumour necrosis factor: strategies for improving the therapeutic index.
AB  - Tumour Necrosis Factor (TNF) is a cytokine initially discovered for its capacity
      to induce haemorrhagic necrosis of experimental tumours and later found to be
      endowed with potent proinflammatory activities. It was soon realised that these
      latter properties were at the origin of unacceptable systemic toxicity in all
      trials aimed at exploiting the anti-tumour activities of TNF. The present review
      intends to reconsider the efforts that have been devoted over the past ten years
      to increase the therapeutic index of TNF so to make it a useful drug for the
      treatment of malignancies. Overall, attempts to achieve this goal with
      systemically administered TNF have met little success so far. On the other hand,
      impressive results have been obtained with locoregional administration of TNF.
      Although of relatively limited clinical utility, these observations have
      indicated a realistic possibility for a therapeutic exploitation of TNF in tumour
      therapy: the delivery of systemically administered TNF to the site of tumour
      growth. On this basis, different targeting and pre-targeting strategies have been
      developed to achieve this goal. While still in their infancy, these approaches
      have yielded encouraging results in experimental tumour models. In the
      forthcoming years it will be possible to evaluate if they represent a practicable
      means of delivering high doses of TNF to the tumour while sparing the organism
      from systemic, toxic effects.

PMID- 9783675
TI  - Nasal route for direct delivery of solutes to the central nervous system: fact or
      fiction?
AB  - During this century, several investigators reported that certain viruses, metals,
      drugs, and other solutes could bypass systemic circulation and enter the brain
      and/or cerebrospinal fluid directly following nasal administration. Although
      evidence clearly suggests that the olfactory epithelium and its olfactory cells
      play a major role, little is known about the mechanisms of direct transport of
      solutes into the brain. An overview of what is known about these mechanisms may
      aid in further research in this field, including studies of direct drug delivery
      to the central nervous system. This review, in addition to summarizing the
      literature to date, clearly describes the intricate association of the anatomical
      features involved in direct entry of solutes into the brain following nasal
      administration. To aid in the understanding of the possible routes a solute can
      take after nasal administration, the anatomy of the olfactory epithelium and
      surrounding tissues is described, and a detailed scheme delineating the emerging
      pathways is presented. Techniques used in delineating these pathways and studies
      supporting a particular pathway are discussed in greater detail. Finally, some
      factors influencing the direct transport of solutes to the cerebrospinal fluid
      and brain are summarized.

PMID- 9783676
TI  - Drug delivery systems for cyclosporine: achievements and complications.
AB  - The review deals with the preparation, properties, and analysis of different
      kinds of cyclosporine delivery systems, such as solid formulations, liposomes,
      emulsions and microemulsions and targeted cyclosporine formulations. The review
      points out a key role of delivery systems in increasing the therapeutic
      effectiveness of cyclosporine. Comparative studies of the prior marketed
      formulation, Sandimmune, with a new microemulsion formulation, Neoral, are
      discussed including some data on clinical development of Neoral.

PMID- 9783677
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- 9783678
TI  - Smaller sized particles are preferentially taken up by alveolar type II
      pneumocytes.
AB  - The uptake of both lung surfactant and other particles from the alveolar space
      plays an essential role in surfactant metabolism, host defense and may be of
      relevance for targeting drugs into alveolar cells. To better understand the
      effect of particle size on the uptake by type II pneumocytes, rat type II cells
      in primary culture were investigated. We observed that inert latex particles of
      15 nm were taken up to a much greater extent than bigger particles. No strong
      size dependency was observed in the range from about 200 to 1000 nm. A similar
      observation was made with a natural lipid extracted lung surfactant which was
      taken up to a greater extent when prepared at particles of about 100 nm than a
      preparation with a particle size range from about 200-2000 nm. Alveolar type II
      cells take up smaller particles better than larger ones, but the size selectivity
      is rather limited. These type II cell properties may contribute to a preferential
      elimination of the smaller particle fractions from the alveolar space.

PMID- 9783679
TI  - Physicochemical characteristics of pentamidine-loaded polymethacrylate
      nanoparticles: implication in the intracellular drug release in Leishmania major
      infected mice.
AB  - This work describes the preparation, the physicochemical properties, the
      tolerance and the intracellular trafficking of pentamidine loaded nanoparticles.
      Pentamidine was bound to the polymer by ionic interaction. This interaction
      involved the carboxylic acid functions of methacrylic acid (10% of the polymer)
      and the amine groups of the drug. Pentamidine fixation and release were pH
      dependent. An acidic pH led to a decrease of fixation or a release. At pH 5,
      which is the pH value of lysosomes and parasitophorous vacuoles, the release
      reached up to 50%. At this pH value, pentamidine is ionized and therefore can not
      traverse the biological membranes. Unloaded nanoparticles and pentamidine-loaded
      nanoparticles were tested in vitro on U937 cells and no cytotoxicity was
      observed. In vivo, in Leishmania infected mice, no significant weight loss was
      found. Ultrastructural studies showed the different steps of drug loaded
      nanoparticles trafficking inside Leismania-infected Kupffer cells. The
      nanoparticle uptake by macrophagic cells led to the location of nanoparticles
      inside phagocytosis vacuoles which fused with primary lysosomes to form secondary
      lysosomes. Ultimate fusion of secondary lysosomes containing nanoparticles with
      parasitophorous vacuoles was also observed. Nanoparticles were identified close
      to amastigotes but internalization by the parasite was not observed.

PMID- 9783680
TI  - Species variation in pharmacokinetics and opsonization of palmitoyl rhizoxin (RS
      1541) incorporated in lipid emulsions.
AB  - Highly lipophilic antitumor agent, palmitoyl rhizoxin (RS-1541), was incorporated
      into stable lipid emulsions about 100-1000nm in mean diameter consisting of
      triglyceride ODO and surfactant HCO-60. The pharmacokinetics of RS-1541 were
      studied after i.v. injection in mice, rats, rabbits, and dogs. Dog showed
      characteristic pharmacokinetics of RS-1541, compared with other species. RS-1541
      was much more rapidly eliminated from plasma with emulsion particles in dogs than
      in mice, rats, and rabbits. Most amounts of injected RS-1541 were recovered in
      the liver six hours after administration to dogs, while less than 20% recoveries
      were observed for mice and rats. To clarify this species variation, opsonization
      of emulsion particles were evaluated. When emulsions (about 200nm in size) were
      opsonized by dog plasma, and intravenously injected to rats, total clearance and
      liver uptake of RS-1541 were increased to 1.8 fold and 2.7 fold of control
      values, respectively. In contrasts, emulsions opsonized by mouse, rabbit and
      human plasma did not show such drastic changes in pharmacokinetics of RS-1541 in
      rats. Furthermore, total clearance of RS-1541 for emulsions opsonized by dog
      plasma was increased to 1.9 fold of controls after injection to rabbits. These
      results indicate that opsonizing activities of dog plasma for RS-1541 emulsions
      are high, compared with other species. This species variation in opsonizing
      process probably caused the species variation in the pharmacokinetics of RS-1541
      incorporated in lipid emulsions.

PMID- 9783681
TI  - In vitro targeting of acoustically reflective immunoliposomes to fibrin under
      various flow conditions.
AB  - We have previously demonstrated the development of acoustically reflective
      liposomes as a novel ultrasound contrast agent, that can be conjugated to
      antibodies for site specific acoustic enhancement of pathologically altered
      vascular tissue. The liposomes are echogenic due to the lipid composition,
      without gas entrapment, and have a size of less than one micron (Alkan-Onyuksel
      et al., 1996). When conjugated to anti-fibrinogen antibodies, the liposomes have
      the ability to attach to fibrin coated surfaces and thrombi in vitro as
      demonstrated by scanning electron microscopy and ultrasound imaging (Demos et
      al., 1997a). Anti-fibrinogen liposomes were shown to attach to fibrous atheroma
      and thrombi in a Yucatan miniswine model of induced atherosclerosis whereas
      liposomes conjugated to anti-intercellular adhesion molecule-1 (anti-ICAM-1) were
      demonstrated to target early stage atherosclerotic plaques (Demos et al., 1997b).
      The purpose of this study is to evaluate the binding characteristics of anti
      fibrinogen liposomes in vitro under a variety of flow conditions in order to
      optimize the targeting ability of the immunoliposomes. Radiolabeled anti
      fibrinogen liposomes were applied to fibrin coated filter paper and placed in a
      flow circuit under controlled flow conditions. Flow conditions were altered to
      study the effects of different shear stresses, temperature, plasma flow and
      pulsatile flow on the retention of liposomes to fibrin after set time periods.
      The retention of liposomes conjugated to polyclonal and monoclonal antibodies as
      well as Fab fragments made from monoclonal antibodies were compared. The binding
      characteristics of liposomes conjugated to different quantities of polyclonal
      antibodies were analyzed. At physiological shear stress of 1.5 N/m2 (15
      dynes/cm2) over 70% of the liposomes remained attached to fibrin after two hours.
      A smaller and greater portion of the liposomes remained attached at higher and
      lower shear stresses respectively. Plasma components and temperature had no
      effect on liposomal retention whereas pulsatile flow resulted in a slight
      reduction in binding. Monoclonal antibodies showed a slight trend of reduced
      retention to fibrin over time as compared with polyclonal antibodies and Fab
      fragments. The quantity of antibody conjugated to the liposomes plays a role in
      liposome retention as demonstrated by the reduction in liposome retention caused
      by reducing the quantity of antibody conjugated to the liposomes. Anti-fibrinogen
      liposomes were retained to the fibrin surface to a large extent under all flow
      conditions likely to occur in vivo and therefore can provide site specific
      ultrasound contrast for a long enough time period to allow for imaging after
      injection.

PMID- 9783682
TI  - Antibody against the Epstein-Barr virus BHRF1 protein, a homologue of Bcl-2, in
      patients with nasopharyngeal carcinoma.
AB  - The Epstein-Barr virus (EBV) open reading frame BHRF1, a homologue of the
      oncogene bcl-2, was cloned from a patient with nasopharyngeal carcinoma (NPC) and
      overexpressed in Escherichia coli. The resulting recombinant BHRF1 fusion
      protein, with an apparent molecular weight of 35 KD, was used as antigen in an
      immunoblotting assay for IgG antibody in human sera. Anti-BHRF1 antibody was
      detected in 57 (61.3%) of 93 patients with NPC, 5 (5.7%) of 87 patients with
      nonmalignant diseases of the nasopharynx, and in 1 (1.3%) of 78 healthy blood
      donors. The positivity rate in these nonmalignant patients was 4.4 times that of
      the normal controls. Negative results were observed in four patients with
      infectious mononucleosis and patients with other cancers, including 4 with
      esophageal cancer, 11 with lung cancer, 10 with lymphoma, 13 with gastric
      carcinoma, 10 with cervical carcinoma, and 10 with other head and neck cancers.
      Antibody neutralizing EBV DNase and IgA antibody to viral capsid antigen (VCA)
      were assayed in parallel. The results showed that 7.5% of the NPC patients were
      negative for anti-DNase and anti-VCA antibodies and EBV infection could be
      detected by the anti-BHRF1 antibody alone. The demonstration of anti-BHRF1
      antibody in most NPC sera strongly supports the hypothesis that the EBV BHRF1
      protein is expressed in most NPC patients and its specific antibody can be a
      useful marker for the diagnosis of NPC.

PMID- 9783684
TI  - Development of antibodies to the nonstructural protein NS1 of parvovirus B19
      during acute symptomatic and subclinical infection in pregnancy: implications for
      pathogenesis doubtful.
AB  - At present little is known about the mechanisms influencing the course and
      severity of parvovirus B19 infection. Antibodies to the parvovirus nonstructural
      protein NS1 were reported in patients with parvovirus-associated arthritis and
      those with persisting infection but not in those without complications,
      suggesting a potential involvement of NS1 or anti-NS1 antibodies in pathogenesis.
      The immune response to NS1 was examined retrospectively in 33 pregnant women with
      acute parvovirus B19 infection, 14 of whom experienced symptomatic infection and
      19 in whom the infection was subclinical. Antibodies to NS1 were found in 15
      (45%) of the women, seven with symptomatic and eight with subclinical infection.
      No association was found between the development of anti-NS1 antibodies and the
      occurrence of fetal complications. Of the seven cases in which fetal
      complications were observed, anti-NS1 antibodies were detected in only three. The
      finding that an immune response to NS1 can also be demonstrated in patients with
      asymptomatic infection suggests that anti-NS1 antibodies do not appear to
      represent a marker for an altered or severe course of infection in pregnant women
      or to contribute significantly to pathogenesis. Since anti-NS1 antibodies first
      become detectable at least six weeks postinfection, their presence can be used to
      exclude acute infection in patients with unclear serology or be used to aid
      differential diagnosis of rashlike illnesses.

PMID- 9783683
TI  - Immunoreactivation of Epstein-Barr virus due to cytomegalovirus primary
      infection.
AB  - Serological diagnosis of herpes virus infections is hampered by concurrent
      expression of IgM for heterologous members of this virus family. To assess the
      frequency of such multiple diagnostic findings and to understand their etiology,
      we sought by using IgG, IgM, and IgG avidity test serodiagnoses for Epstein-Barr
      virus (EBV) among immunocompetent or immune-suppressed patients with well
      documented cytomegalovirus (CMV) primary infection. Controls had primary
      infection by EBV or had acute septic or severe respiratory infection. Among EBV
      seropositive patients with CMV primary infection, a large proportion (13/56, 23%)
      showed antibody profiles of EBV reactivation: seroconversion of VCA IgM and/or >
      or = fourfold rise of VCA IgG, together with high or intermediate avidity of VCA
      IgG. Most of the CMV patients with EBV serodiagnosis showed also diagnostic HHV-6
      antibody rises. In contrast to the frequently occurring CMV-induced EBV
      immunoreactivation, EBV primary infections did not appear to induce
      immunoreactivations of CMV (0/22). Only one (2%) CMV patient had a significant
      varicella zoster virus (VZV) antibody rise. The studies show that CMV is a
      particularly active inducer of some, but not all, members of the herpes virus
      family and suggest that the in vivo interplay between CMV and EBV occurs
      unidirectionally. The high frequency of heterologous herpes virus
      immunoreactivations poses demands on laboratory diagnosis.

PMID- 9783685
TI  - Presence and significance of human parvovirus B19 DNA in synovial membranes and
      bone marrow from patients with arthritis of unknown origin.
AB  - Acute rheumatologic symptoms are frequently associated with human parvovirus B19
      (B19) infections. A nested PCR (nPCR) assay was used to test for the presence of
      parvovirus B19 DNA in synovial fluid and/or synovial membrane specimens obtained
      from a total of 90 patients with arthritis of unknown origin. Whereas only one
      out of 73 synovial fluid samples were found positive, 15 (16.7%) out of 90
      patients had parvovirus B19 DNA in the synovium. B19 virus DNA was detected in
      nine bone marrow aspirates subsequently obtained from these 15 patients (60%).
      Whereas each one of the 15 corresponding blood samples contained anti-B19 IgG
      antibody, none contained anti-B19 IgM antibody and only one was positive for B19
      virus DNA. The blood and synovial fluid samples that contained B19 virus DNA were
      obtained from the same patient, who also had B19 DNA in synovium and bone marrow.
      For one patient, two distinct synovial membrane specimens collected 10 months
      apart tested positive for B19 virus DNA. Parvovirus B19 DNA was also detected in
      synovial tissue of one out of nine nonarthritic patients serving as control
      group, who also had anti-B19 IgG circulating antibody. These data illustrate that
      human parvovirus B19 may persist in bone marrow and synovial tissues of patients
      with arthritis of unknown origin. In contrast, persistence of B19 virus DNA in
      synovial fluid is rare. The significance of parvovirus B19 DNA in synovium of
      healthy patients has to be established.

PMID- 9783686
TI  - Analysis of genetic diversity in the VP1 unique region gene of human parvovirus
      B19 using the mismatch detection method and direct nucleotide sequencing.
AB  - To assess the prevalent genetic types of human parvovirus B19 strains derived
      from various sources and their relation to particular clinical symptoms, the
      genetic diversity in the VP1 unique region, which is important for the
      neutralizing response to human parvovirus B19, was examined by the mismatch
      detection method using the Non-isotopic RNase Cleavage Assay (NIRCA) and direct
      nucleotide sequencing. Twenty three samples obtained between 1986 and 1997 were
      examined. Three electrophoresis patterns were observed with NIRCA. The nucleotide
      sequence showed that there were 14 nucleotide changes and 4 amino acid
      substitutions in comparison with Au strains employed as a standard strain. The
      nucleotide variability of all samples ranged from 0.3 to 2.7% and the amino acid
      variability ranged from 1.0 to 3.0%. They were classified into three types
      according to NIRCA. Types 1 and 3 had similar sequences, but the type 2 sequence
      was quite different. Although there were some nucleotide variations in the same
      NIRCA type, these were silent. However, there was no relationship between the
      clinical features and NIRCA types or between clinical features and the nucleotide
      sequence. All samples obtained before 1987 were NIRCA type 2. On the other hand,
      19 of 20 samples obtained after 1989 were NIRCA type 1. The other sample obtained
      in 1992 was type 3. The results suggest that the B19 strain of type 2 disappeared
      by 1988 and changed to other B19 strains such as type 1 and type 3 after 1988,
      indicating a correlation between genome type and prevalence. NIRCA is a
      convenient method for screening mutations due to its simplicity and quickness.

PMID- 9783687
TI  - Presence of antibodies to human papillomavirus virus-like particles (VLPs) in 11
      13-year-old schoolgirls.
AB  - To allow meaningful approaches to vaccine development, it is important to know
      the extent of exposure to human papillomavirus (HPV) within the general
      population, and particularly the age at which the at risk population is infected.
      The humoral response to human papillomavirus is directed largely to
      conformationally-dependent epitopes on the whole virion. Virus-like particles
      (VLPs) of HPV types 1, 2, and 16 were produced using a baculovirus expression
      system, and were used in the intact state as antigen in an indirect ELISA.
      Anonymised serum samples from a cohort of Edinburgh schoolgirls were tested for
      the presence of IgG antibodies directed against the VLPs. The reproducibility of
      the ELISA was assured by repeated testing of control samples, and by testing all
      samples in duplicate and, where possible, on several occasions. Of 1,192 tested
      with the HPV16 VLPs, 90 (7.6%) were classified as clearly positive, and a further
      87 (7.3%) were positive but close to the cutoff calculated by comparison with a
      group of consistently negative sera. Antibodies to HPV2 were detected in 37.5%
      (407/1,139) and antibodies to HPV 1 in 51.9% (558/1,076) of the schoolgirls.
      Antibodies to both HPV1 and HPV2 were found frequently, being present in 29.7%
      (295/ 993) of samples tested; 40 samples had antibodies to all three types. The
      significance of these results is discussed.

PMID- 9783688
TI  - Expression of interferon alpha/beta receptor in the liver of chronic hepatitis C
      patients.
AB  - Interferon (IFN) demonstrates antiviral activity by binding to receptors on the
      cell surface. Expression of the IFN receptor in hepatocytes may be directly
      associated with a hepatitis C virus (HCV) infection and the response to IFN
      therapy. A competitive PCR method was developed to measure IFN alpha/beta
      (alphabeta) receptor mRNA in liver samples obtained by needle biopsy. Thirty-one
      patients with chronic hepatitis C (21 without cirrhosis, 10 with cirrhosis) and
      six normal subjects were used. Eighteen of the 21 patients without cirrhosis
      received the IFN therapy. Competitive PCR was carried out using IFN alphabeta
      receptor gene-specific primers and a specific competitor. Expression of the
      receptor was detected in all liver samples. There was no association between the
      expression level and serum alanine aminotransferase level, serum (2'-5') oligo
      (A) synthetase level, amount of serum HCV RNA, or HCV genotype. The expression
      level in patients with chronic hepatitis was significantly higher than that in
      normal livers (P < 0.05) and in cirrhotic livers (P< 0.01). Seven of the 18
      patients treated with IFN demonstrated a sustained response to IFN (sustained
      responders), and the remaining 11 did not (nonsustained responders). The
      expression level of IFN alphabeta receptor mRNA in the sustained responders was
      significantly higher than that in the nonsustained responders (P< 0.01). Thus,
      the expression of IFN alphabeta receptor mRNA may be one of the host factors
      influencing the response to IFN therapy.

PMID- 9783689
TI  - IgM anti-hepatitis C virus core antibodies as marker of recurrent hepatitis C
      after liver transplantation.
AB  - The differential diagnosis of recurrent hepatitis C following orthotopic liver
      transplantation (OLT) may be difficult. We evaluated the diagnostic significance
      of IgM anti-hepatitis C virus (anti-HCV) core antibodies in 27 patients
      undergoing OLT because of HCV-associated cirrhosis. Serial serum samples
      collected before and after OLT were tested for the presence of IgM anti-HCV core
      antibodies. Results were compared with the histological evidence of liver damage,
      the presence, level, and genotype of serum HCV RNA and the degree of
      immunosuppression. All patients underwent recurrent HCV infection. Recurrent
      hepatitis was diagnosed histologically in 21 patients an average of 48 weeks
      after OLT (range 2-209 weeks): 18 had persistence or (re-)appearance of the IgM
      anti-HCV core after OLT, one lost the IgM anti-HCV core after OLT, and two never
      secreted IgM anti-HCV core either before or after OLT. The remaining six patients
      did not develop recurrent hepatitis after a follow-up of 44-241 weeks from OLT;
      in these patients, IgM anti-HCV core either disappeared (1 case) or decreased (1
      case) after OLT or were persistently negative throughout the study (4 cases).
      Thus, 18/21 patients with recurrent hepatitis, but only one of six without
      recurrent hepatitis, secreted IgM anti-HCV core after OLT (P < 0.05). The IgM
      anti-HCV core levels were not correlated with the level or genotype of serum HCV
      RNA or the degree of immunosuppression. In conclusion, secretion of IgM anti-HCV
      core antibodies after OLT seems associated with recurrence of HCV-associated
      liver disease and may have diagnostic significance.

PMID- 9783690
TI  - Hepatitis C virus infection and genotypes in Southern Israel and the Gaza Strip.
AB  - The Gaza Strip borders the southern part of Israel and Egypt. There is a
      remarkable difference in the prevalence of antibodies to hepatitis C virus (HCV)
      between Israel (0.5%) and Egypt (10%). A few thousand inhabitants cross the
      borders daily from the Gaza Strip to both countries. The objectives of this study
      were to investigate the prevalence of HCV infection in the Gaza Strip, an area
      that was not studied before, and to study HCV transmission in the Gaza Strip by
      characterizing the genotypes of HCV in Southern Israel and the Gaza Strip and
      comparing them with those found in Egypt. HCV prevalence in the Gaza Strip was
      found to be 2.2%, relatively higher than in Israel but lower than in Egypt. The
      most common genotypes found were type 1 b in Southern Israel and type 4 in the
      Gaza Strip, corresponding to the most prevalent genotype in Egypt. Similarity
      between type 4 isolates from the Gaza Strip and Egypt was illustrated further by
      sequence analysis of the HCV 5' noncoding region (NCR).

PMID- 9783691
TI  - Infection with an unenveloped DNA virus (TTV) associated with posttransfusion non
      A to G hepatitis in hepatitis patients and healthy blood donors in Thailand.
AB  - An unenveloped single-stranded DNA virus (TTV) has been reported in association
      with posttransfusion and acute and chronic hepatitis of unknown etiology. DNA of
      TTV was tested for by polymerase chain reaction with heminested primers in 127
      patients with chronic liver disease and 105 healthy blood donors in Thailand. TTV
      DNA was detected in 23 (59%) of the 39 patients without hepatitis B surface
      antigen or RNA of hepatitis C virus, at a frequency significantly higher than the
      detection in 21 (36%) of the 59 patients with HBsAg (P < 0.05) or in 38 (36%) of
      the 105 blood donors (P< 0.05). Among patients with chronic liver disease, TTV
      DNA occurred in those with liver cirrhosis and hepatocellular carcinoma more
      frequently than in those with chronic hepatitis (35 of 65 or 54% vs. 20 of 62 or
      32%, P< 0.05). There were no differences in age, sex, or markers of infection
      with hepatitis B, C and GBV-C/HGV viruses, indicating a mode of transmission of
      TTV different from those of the other hepatitis viruses. Phylogenetic analysis
      indicated three different genotypes of TTV with six distinct subtypes in
      Thailand. Based on these results, TTV would have a role in the development of
      chronic liver disease of unknown etiology in Thailand.

PMID- 9783692
TI  - Hepatitis C and human immunodeficiency virus RNA degradation by methylene
      blue/light treatment of human plasma.
AB  - Treatment of human plasma with methylene blue in combination with visible light
      (MB/light) inactivates several bloodborne viruses such as retro viruses and
      herpes viruses. The viral nucleic acid is thought to be a critical target for the
      inactivation procedure. We investigated the effects of photodynamic treatment on
      the RNA of hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV
      1) using Amplicor reverse transcriptase polymerase chain reaction (RT-PCR), which
      detects and quantifies a small fragment of the viral RNA. The detectable HCV RNA
      load (5-nontranslated region) in infected human plasma declined by 94-97 % within
      10 min of illumination in small-scale experiments (1-2 ml vol.). Since the same
      effect was observed in both anti-HCV positive and negative ("window") samples, it
      can be concluded that HCV antibodies do not influence virus inactivation by
      photodynamic treatment. The effect of treatment on RT-PCR signals of HIV-1, which
      is known to be inactivated rapidly by MB/light treatment, was examined. Plasma
      was infected with HIV-1 and subjected to RT-PCR, which detected a part of the gag
      gene. The extent and kinetics of PCR signal reduction induced by MB/light
      treatment were similar to those observed for HCV. Experiments at production scale
      where single plasma units (300 ml) were infected with HCV showed reduction rates
      of PCR signals consistent with those measured in the small-scale experiments. The
      data support the view that MB/light treatment affects the viral nucleic acids and
      suggest that HCV is susceptible to the procedure.

PMID- 9783693
TI  - Prevalence patterns and genotypes of GB virus C/hepatitis G virus among
      imprisoned intravenous drug users.
AB  - An RT-PCR assay using primers from the 5'-UTR of the GBV-C/HGV genome was used to
      detect viremia, and a serological assay was used to detect past exposure to GBV
      C/HGV, in sera from 106 imprisoned Greek intravenous drug users. High
      seroprevalence rates indicative of the parenteral route of transmission of the
      virus were found (32.1% for GBV-C RNA and 46.2% for anti-GBV-C E2). These rates
      were nonetheless lower in comparison to the corresponding rates of HCV infection
      markers (64.2% for HCV RNA and 77.4% for anti-HCV). Statistically significant
      univariate associations were observed between GBV-C-RNA positivity and younger
      age (P=0.006) and HCV-RNA positivity (P=0.024), as well as with higher serum
      alanine aminotransferase levels (P< 0.001); this latter association was shown to
      be independent of coinfection with HCV and of age by a multiple logistic
      regression model. Apparently, GBV-C/HGV had spread readily by needle-sharing in
      prison, while causing acute subclinical hepatitis in infected inmates.
      Phylogenetic analysis of the partial 5'-UTR of the GBV-C/HGV genome from 16
      seropositive individuals, which delineated their grouping within genotype 2, also
      revealed a close genetic relationship between two sets of sequences from 4 drug
      addicts, 3 of whom admitted to sharing needles while imprisoned.

PMID- 9783694
TI  - Antienvelope antibodies are protective against GBV-C reinfection: evidence from
      the liver transplant model.
AB  - An assay for the detection of antibody against the second envelope (E2) protein
      of GB virus type C (GBV-C) has been developed. Early reports suggested that this
      antibody was a marker of viral clearance, yet it is unknown whether anti-E2 is
      protective against further GBV-C infection. The primary aims were to determine
      (1) if posttransplantation immunosuppression alters the prevalence of anti-E2;
      and (2) if anti-E2 positivity pretransplantation protects against acquisition of
      GBV-C infection posttransplantation. Fifty-four recipients who underwent
      orthotopic liver transplantation for end-stage liver disease of nonviral
      etiologies were tested for GBV-C RNA using a PCR-based assay and anti-E2
      antibodies by an enzyme-linked immunoassay. Anti-E2 was present in 35% and in 46%
      of patients pre- and posttransplantation, respectively. Anti-E2 positivity
      pretransplantation was strongly associated with anti-E2 positivity after
      transplantation (P < 0.001); 83% of patients with anti-E2 prior to
      transplantation remained anti-E2-positive after transplantation. A negative
      association between presence of GBV-C viremia and presence of anti-E2 was found
      in all patients tested either prior to or following transplantation (P=0.03).
      Acquisition of GBV-C infection was significantly lower in patients who were anti
      E2-positive prior to transplantation (2/13) compared to those who were anti-E2
      negative (12/26) (P=0.05). It is concluded that immunosuppression does not reduce
      the prevalence of anti-E2 after transplantation in those who are seroreactive
      prior to transplantation. Anti-E2 appears to be a neutralizing antibody whose
      presence at the time of liver transplantation protects against acquisition of GBV
      C infection in the peritransplantation period.

PMID- 9783695
TI  - Role of HIV-1 phenotype in viral pathogenesis and its relation to viral load and
      CD4+ T-cell count.
AB  - The predictive value of HIV-1 phenotype in peripheral blood mononuclear cell
      (PBMC) coculture and the relation among viral phenotype, viral load, and CD4+ T
      cell count were examined in two studies. In study A, 132 HIV-1-infected
      individuals were examined retrospectively for the relation between the result of
      their initial HIV cultivation in PBMC coculture and survival rate 6 years later.
      In study B, 176 patients were examined since 1994 for markers of HIV disease
      progression. HIV-1 phenotype was determined by PBMC cocultivation, viral load by
      NASBA HIV RNA QT System, and CD4+ T-cell count by flow cytometry. In study A, the
      percentage of survival for patients with initial negative virus culture was
      significantly higher (95%) than in patients with nonsyncytia-inducing (NSI)
      isolates (78%) and syncytia-inducing (SI) isolates (21%) (P < 0.05 and P< 0.0001,
      respectively). When SI phenotype was subdivided into moderately cytopathogenic
      and highly cytopathogenic, significant differences in the rate of survival
      between these subgroups could be observed (45% vs. 14%; P < 0.05). In study B,
      progression from negative virus culture to the isolation of NSI variants was
      associated with increasing viral load (P < 0.0001) but did not affect CD4+ T-cell
      count significantly (P> 0.07), whereas the switch from NSI to SI virus was
      accompanied by significant decline of CD4+ T-cells (P < 0.0001) but no change in
      viral load (P > 0.21). Thus, isolation and phenotyping of HIV represents an
      additional striking predictive marker for progression of HIV infection.

PMID- 9783696
TI  - Neutralization of HIV-1 subtypes: implications for vaccine formulations.
AB  - More than 20.8 million people are infected with HIV in sub-Saharan Africa, with
      South Africa having one of the fastest growing HIV-1 epidemics, where an
      estimated 2.4 million people were infected. Thirty-two sera from 25 patients were
      tested for their ability to neutralize HTLV-IIIB (IIIB) and four primary isolates
      representing subtypes B, C, D, and a recombinant gag C/env B type. A CEM-SS cell
      line-based assay was used and the neutralizing titer was defined as the
      reciprocal of the highest dilution giving a 50% reduction in p24 antigen
      production. All isolates were neutralized better by subtype-specific sera, except
      for the C4714 strain, which was neutralized by both subtype B and C sera. C4714
      was neutralized by 18/25 (72%) sera, IIIB by 19/32 (59%) sera, D482 by 7/31(23%)
      sera, B3245 by 6/29 (21%) sera, and the recombinant B/C1491 isolate by 4/25 (16%)
      sera. Five sera were unable to neutralize any of the isolates. The V3 region of
      the isolates used in the neutralization assay was amplified by PCR, directly
      sequenced, and analyzed to reveal variability between the consensus HIV-1
      sequences and the isolates. HIV-1 strain C4714 was neutralized more effectively
      with the sera tested than the IIIIB laboratory strain. Variability in the amino
      acid sequence of the V3 region, which can alter the conformation of the V3 loop
      secondary structure, can influence the neutralization of a particular viral
      isolate. Vaccine formulations should be broadened to include multiple subtypes,
      especially C subtypes, which is rapidly spreading worldwide.

PMID- 9783697
TI  - Ethnic cluster of HTLV-I infection in Israel among the Mashhadi Jewish
      population.
AB  - A high prevalence of human T-lymphotropic virus type I (HTLV-I) infection among
      Israeli Jews was previously reported. In the present study, screening for HTLV-I
      of Israeli Jews was expanded to 10 ethnic groups. HTLV-I antibodies were tested
      by the particle agglutination assay, ELISA, and by Western blot as a confirmatory
      method. The HTLV-I proviral genome was tested by nested PCR with tax primers
      (SK43/SK44 and Tr101/Tr102). The PCR tests were carried out in all seropositive
      subjects and the seronegative family members of the seropositives subjects in the
      Iranian population. Sixty-eight of the 1,679 subjects (4.1%) were found to be
      seropositive. The Jews originating from Mashhad had the highest infection rate of
      60/306 (20%). Of the 479 Iranian non-Mashhadi Jews, 6 (1.3%) were seropositive.
      Of the 894 non-Iranian Israelis, only 2 (0.2%) were seropositive. HTLV-I proviral
      DNA was found in the peripheral blood lymphocytes of 66 out of 68 seropositive
      subjects and 6 out of 75 seronegative subjects. Sixty out of 123 (49%) Mashhadi
      Jews and 8 out of 14 (57%) non-Mashhadi Iranian Jews were PCR-positive. Three out
      of three seropositive non-Iranian Israelis were PCR positive. One non-Iranian
      Israeli (who originated from Ukraine) without family connections to the Iranian
      Jews was also PCR-positive. One hundred eighteen saliva samples (84 from subjects
      of Mashhadi origin, 31 from Iranian origin, and 4 of other origins) were also
      screened. Antibodies for HTLV-I were found in 23 out of 46 saliva samples from
      the individuals with particle agglutination (PA) and/or PCR-positive findings in
      blood. Twenty out of 23 PA-positive saliva samples also contained the proviral
      DNA. It is concluded that HTLV-I infection in Israel is mainly limited to Jews
      originating from Iran (most of them from Mashhad) and their family members.

PMID- 9783698
TI  - Detection of human herpesvirus 7 (HHV-7) DNA in breast milk by polymerase chain
      reaction and prevalence of HHV-7 antibody in breast-fed and bottle-fed children.
AB  - Twenty-nine breast milk mononuclear cell samples were analyzed for human
      herpesvirus 7 (HHV-7) DNA, human herpesvirus 6 (HHV-6) DNA, and human
      cytomegalovirus (HCMV) DNA by polymerase chain reaction (PCR). In addition,
      peripheral blood mononuclear cell samples from 13 puerperants were analyzed for
      HHV-7 DNA by PCR, and seropositivity of HHV-7 was also analyzed in breast-fed and
      bottle-fed children. HHV-7 DNA was detected in 3 of 29 breast milk samples. HCMV
      DNA was also detected in 3 of 29 breast milk samples, but HHV-6 DNA was not
      detected. HHV-7 DNA was detected in 11 of 13 samples of peripheral blood
      mononuclear cells. Though the seropositivity rate for HHV-7 in breast-fed
      children was slightly higher than that in bottle-fed children at 18 and 24 months
      old, the difference was not statistically significant. From these results, we
      speculate that breast-feeding may be one of the transmission routes of HHV-7,
      although this is not the main route.

PMID- 9783699
TI  - Elevated levels of IL-8 in dengue hemorrhagic fever.
AB  - Dengue virus causes dengue fever, a mild febrile illness, and at times dengue
      hemorrhagic fever (DHF), a severe illness the pathogenesis of which is not fully
      understood. Given the crucial roles played by interleukin-8 (IL-8) as a
      chemoattractant cytokine and in inflammatory processes, levels of circulating IL
      8 in the sera and IL-8 mRNA in the peripheral blood mononuclear cells (PBMC) were
      measured in 99 patients of a recent dengue epidemic that occurred in India in
      1996 and in 21 normal healthy controls. Twenty-six of the patients had dengue
      fever (DF) and the remaining 73 were diagnosed as having different grades of DHF.
      All the control normal sera were negative for IL-8, so were their PBMC for IL-8
      mRNA. Increased levels of IL-8 in the sera and IL-8 mRNA in their PBMC were
      observed in patients with severe illness of DHF grades III and IV. Only two out
      of 26 patients of DF and one out of 10 DHF grade I patient were positive for IL-8
      and all three deteriorated to DHF grade IV within 24 hr. All six patients of DHF
      grade IV who died had higher serum level of IL-8 above 200 pg/ml, the highest
      being 5,568 pg/ml in one patient; the presence of mRNA for IL-8 was very high in
      all patients. A striking correlation was observed between increased levels of IL
      8 and severe DHF, with greater levels in patients with increased grade of the
      disease and death. These results suggest that IL-8 may have an important role and
      may be an indicator of increasing severity of the disease and death.

PMID- 9783701
TI  - Localisation of a gene for non-specific X linked mental retardation (MRX46) to
      Xq25-q26.
AB  - We report linkage data on a new large family with non-specific X linked mental
      retardation (MRX), using 24 polymorphic markers covering the entire X chromosome.
      We could assign the underlying disease gene, denoted MRX46, to the Xq25-q26
      region. MRX46 is tightly linked to the markers DXS8072, HPRT, and DXS294 with a
      maximum lod score of 5.12 at theta=0. Recombination events were observed with
      DXS425 in Xq25 and DXS984 at the Xq26-Xq27 boundary, which localises MRX46 to a
      20.9 cM (12 Mb) interval. Several X linked mental retardation syndromes have been
      mapped to the same region of the X chromosome. In addition, the localisation of
      two MRX genes, MRX27 and MRX35, partially overlaps with the linkage interval
      obtained for MRX46. Although an extension of the linkage analysis for MRX35
      showed only a minimal overlap with MRX46, it cannot be excluded that the same
      gene is involved in several of these MRX disorders. On the other hand, given the
      considerable genetic heterogeneity in MRX, one should be extremely cautious in
      using interfamilial linkage data to narrow down the localisation of MRX genes.
      Therefore, unless the underlying gene(s) is characterised by the analysis of
      candidate genes, MRX46 can be considered a new independent MRX locus.

PMID- 9783700
TI  - Clinical features, molecular genetics, and pathophysiology of dominant optic
      atrophy.
AB  - Inherited optic neuropathies are a significant cause of childhood and adult
      blindness and dominant optic atrophy (DOA) is the most common form of autosomally
      inherited (non-glaucomatous) optic neuropathy. Patients with DOA present with an
      insidious onset of bilateral visual loss and they characteristically have
      temporal optic nerve pallor, centrocaecal visual field scotoma, and a colour
      vision deficit, which is frequently blue-yellow. Evidence from histological and
      electrophysiological studies suggests that the pathology is confined to the
      retinal ganglion cell. A gene for dominant optic atrophy (OPA1) has been mapped
      to chromosome 3q28-qter, and studies are under way to refine the genetic interval
      in which the gene lies, to map the region physically, and hence to clone the
      gene. A second locus for dominant optic atrophy has recently been shown to map to
      chromosome 18q12.2-12.3 near the Kidd blood group locus. The cloning of genes for
      dominant optic atrophy will provide important insights into the pathophysiology
      of the retinal ganglion cell in health and disease. These insights may prove to
      be of great value in the understanding of other primary ganglion cell diseases,
      such as the mitochondrially inherited Leber's hereditary optic neuropathy and
      other diseases associated with ganglion cell loss, such as glaucoma.

PMID- 9783702
TI  - The prevalence of PAX2 mutations in patients with isolated colobomas or colobomas
      associated with urogenital anomalies.
AB  - The PAX2 gene is mutated in patients with ocular colobomas, vesicoureteral reflux
      (VUR), and kidney anomalies (renal-coloboma syndrome, OMIM 120330). The three
      abnormalities which make up this syndrome also occur in isolation, but the causal
      genes are not known. PAX2 encodes a transcription factor of the paired box class
      of DNA binding proteins, important for the development of the urogenital tract,
      optic nerve and adjacent retina, inner ear, and CNS. In this paper we have
      investigated the prevalence of PAX2 mutations in patients with ocular colobomas,
      microphthalmos, or retinal anomalies, either in isolation or with associated
      urogenital anomalies. Using PCR-SSCP, most or all exons of PAX2 were examined in
      blood DNA from 99 patients who have either ocular anomalies alone or a
      combination of ocular and urogenital conditions. PAX2 mutations were not detected
      in patients with ocular colobomas, either in isolation or with associated
      abnormalities, except in one patient with typical renal-coloboma syndrome. We
      conclude that PAX2 mutations are unlikely to be common in patients with ocular
      colobomas in isolation or in patients with ocular colobomas and associated
      anomalies, except for patients with typical renal-coloboma syndrome where PAX2 is
      known to be the aetiological cause.

PMID- 9783704
TI  - Parental origin effects in human trisomy for chromosome 14q: implications for
      genomic imprinting.
AB  - Parental origin specific congenital anomalies have been noted in patients with
      uniparental disomy of the long arm of human chromosome 14 (UPD14). This suggests
      the presence of imprinted genes, consistent with observations of imprinting in
      the region of syntenic homology in the mouse. It is not known whether the
      distinct defects reported for paternal and maternal UPD14 are the result of
      biallelic expression or absence of expression of imprinted genes. Furthermore,
      identification of the genes responsible would be facilitated by a higher
      resolution map of the imprinted region(s) involved. Subjects with partial trisomy
      for chromosome 14 (Ts14) have been reported and hence also have an alteration in
      the dosage of their parental chromosomes. In this study, we have carried out
      genotype-phenotype correlations considering the parental origin of the extra
      chromosome in previously reported cases of maternal and paternal partial Ts14.
      The analysis has provided evidence of a correlation between distal maternal Ts14
      and anomalies including low birth weight, short philtrum, and small hands. The
      clinical features found in the maternal and paternal trisomies are compared with
      those associated with maternal and paternal UPD14 and their significance is
      discussed in relation to genomic imprinting on chromosome 14.

PMID- 9783705
TI  - A common DLX3 gene mutation is responsible for tricho-dento-osseous syndrome in
      Virginia and North Carolina families.
AB  - Tricho-dento-osseous syndrome (TDO) is characterised by a variable clinical
      phenotype primarily affecting the hair, teeth, and bone. Different clinical
      features are observed between and within TDO families. It is not known whether
      the variable clinical features are the result of genetic heterogeneity or
      clinical variability. A gene for TDO was localised recently to chromosome 17q21
      in four North Carolina families, and a 4 bp deletion in the human distal-less 3
      gene (DLX3) was identified in all affected members. A previous genetic linkage
      study in a large Virginia kindred with TDO indicated possible linkage to the ABO,
      Gc, and Kell blood group loci. To examine whether TDO exhibits genetic
      heterogeneity, we have performed molecular genetic analysis to determine whether
      affected members of this Virginia kindred have the DLX3 gene deletion identified
      in North Carolina families. Results show that affected subjects (n=3) from the
      Virginia family have the same four nucleotide deletion previously identified in
      the North Carolina families. A common haplotype for three genetic markers
      surrounding the DLX3 gene was identified in all affected subjects in the North
      Carolina and Virginia families. These findings suggest that all people with TDO
      who have been evaluated have inherited the same DLX3 gene deletion mutation from
      a common ancestor. The variable clinical phenotype observed in these North
      Carolina and Virginia families, which share a common gene mutation, suggests that
      clinical variability is not the result of genetic heterogeneity at the major
      locus, but may reflect genetic heterogeneity at other epigenetic loci or
      contributing environmental factors or both.

PMID- 9783703
TI  - Neurofibromatosis type 1 (NF1): a protein truncation assay yielding
      identification of mutations in 73% of patients.
AB  - Neurofibromatosis type 1 (NF1) is caused by mutations in a tumour suppressor gene
      located on chromosome 17 (17q11.2). Disease causing mutations are dispersed
      throughout the gene, which spans 350 kilobases and includes 59 exons. A common
      consequence of NF1 mutations is introduction of a premature stop codon, and the
      majority of mutant genes encode truncated forms of neurofibromin. We used a
      protein truncation assay to screen for mutations in 15 NF1 patients and obtained
      positive results in 11 of them (73%). Sequencing of cDNA and genomic DNA yielded
      identification of 10 different mutations, including four splicing errors, three
      small deletions, two nonsense mutations, and one small insertion. Nine mutations
      were predicted to cause premature termination of translation, while one mutation
      caused in frame deletion as a result ofexon skipping. In one other case involving
      abnormal splicing, five different aberrantly spliced transcripts were detected.
      One germline nonsense mutation (R1306X, 3916C>T) corresponded to the same base
      change that occurs by mRNA editing in normal subjects. The second nonsense
      mutation (R2496X) was the sole germline mutation that has been previously
      described. The subjects studied represented typically affected NF1 patients and
      no correlations between genotype and phenotype were apparent. A high incidence of
      ocular hypertelorism was observed.

PMID- 9783707
TI  - A FISH study of chromosome fusion in the ICF syndrome: involvement of paracentric
      heterochromatin but not of the centromeres themselves.
AB  - We have used double fluorescence in situ hybridisation to study the involvement
      of centromeres and paracentromeric heterochromatin in the chromosome
      abnormalities seen in the ICF syndrome. To detect centromeres, we used a probe
      which labelled alphoid satellite DNA, and for the paracentromeric heterochromatin
      a probe for classical satellite II. Our results show that it is always the
      paracentromeric heterochromatin of the relevant chromosomes that becomes
      decondensed in this syndrome and which fuses to produce multiradial
      configurations. However, the centromeric regions, identified by their content of
      alphoid satellite DNA, appear never to become decondensed and always remain
      outside the regions of chromosome fusion in the multiradials.

PMID- 9783706
TI  - Isolation of BAC clones spanning the Xq22.3 translocation breakpoint in a
      lissencephaly patient with a de novo X;2 translocation.
AB  - X linked lissencephaly and subcortical band heterotopia (XLIS/SBH) is a disorder
      of cortical development, which causes classical lissencephaly with severe mental
      retardation and epilepsy in hemizygous males and SBH associated with milder
      mental retardation and epilepsy in heterozygous females. Here we report the fine
      mapping of a breakpoint involved in a de novo X;autosomal balanced translocation
      (46,XX,t(X;2) (q22.3;p25.1)) previously described in a female with classical
      lissencephaly. We constructed a complete 490 kb BAC contig around the Xq22.3
      breakpoint with 11 novel STSs and isolated three BAC clones spanning the
      breakpoint. This mapping information and BAC contig will be useful in the
      detailed characterisation of the XLIS gene and other contiguous genes which may
      also be involved in brain development or function.

PMID- 9783708
TI  - Mosaic supernumerary ring chromosome 19 identified by comparative genomic
      hybridisation.
AB  - We report the use of comparative genomic hybridisation (CGH) to define the origin
      of a supernumerary ring chromosome which conventional cytogenetic banding and
      fluorescence in situ hybridisation (FISH) methods had failed to identify.
      Targeted FISH using whole chromosome 19 library arm and site specific probes then
      confirmed the CGH results. This study shows the feasibility of using CGH for the
      identification of supernumerary marker chromosomes, even in fewer than 50% of
      cells, where no clinical or cytogenetic clues are present.

PMID- 9783709
TI  - Familial cylindromatosis mimicking tuberous sclerosis complex and confirmation of
      the cylindromatosis locus, CYLD1, in a large family.
AB  - A large Dutch family had been known for many years to be affected with skin
      tumours labelled as adenoma sebaceum, which were inherited in an autosomal
      dominant fashion. Since this skin sign is considered pathognomonic for tuberous
      sclerosis complex, the condition in the family was labelled accordingly, in the
      absence of further clinical features of tuberous sclerosis complex-like mental
      retardation or epilepsy. The skin changes started at early puberty with small
      eruptions around the nose and progressed to larger tumours, with considerable
      variation in severity. Some affected members had required plastic surgical
      reconstruction following excision. Linkage analysis in this family was performed
      for the two chromosomal regions involved in tuberous sclerosis complex on
      chromosomes 9q34 and 16p13, but no positive linkage was found. On critical re
      evaluation of the clinical and pathological data and renewed assessment, the
      working diagnosis was changed to autosomal dominant cylindromatosis. The recently
      published candidate region for cylindromatosis on chromosome 16q12-13 was
      subsequently proven to be positively linked with a lod score of 3.02 with marker
      D16S308. Review of pathological specimens confirmed the diagnosis of
      cylindromatosis. DNA analysis of tumour tissue showed loss of heterozygosity for
      the cylindromatosis CYLD1 locus. These results confirm the candidate locus for
      cylindromatosis on chromosome 16q12-13.

PMID- 9783710
TI  - A single base mutation in COL5A2 causes Ehlers-Danlos syndrome type II.
AB  - Ehlers-Danlos syndrome (EDS) is a heterogeneous group of connective tissue
      disorders. Recently mutations have been found in the genes for type V collagen in
      a small number of people with the most common forms of EDS, types I and II. Here
      we characterise a COL5A2 mutation in an EDS II family. Cultured dermal
      fibroblasts obtained from an affected subject synthesised abnormal type V
      collagen. Haplotype analysis excluded COL5A1 but was concordant with COL5A2 as
      the disease locus. The entire open reading frame of the COL5A2 cDNA was directly
      sequenced and a single base mutation detected. It substituted a glycine residue
      within the triple helical domain (G934R) of alpha2(V) collagen, typical of the
      dominant negative changes in other collagens, which cause various other inherited
      connective tissue disorders. All three affected family members possessed the
      single base change, which was absent in 50 normal chromosomes.

PMID- 9783711
TI  - Fibroblast silver loading for the diagnosis of Menkes disease.
AB  - Menkes disease is a genetic disorder of copper metabolism. Copper uptake and
      retention assays on fibroblast or amniotic fluid cell cultures have been used for
      pre- and postnatal diagnosis. These copper loading tests are complicated by the
      use of 64Cu, which is not commonly available and has a very short (12.8 hours)
      physical half life. Besides copper, silver is also a substrate for the bacterial
      homologue of the Menkes transport protein. We report here that loading tests
      using radioactive silver (110mAg), instead of copper, can be used for the
      diagnosis of Menkes disease. 110mAg is commercially available and has a
      convenient physical half life of 250 days, which makes it suitable for use in
      diagnostic laboratories. Our studies support the hypothesis that reduction of
      divalent to monovalent copper is an essential step preceding transport.

PMID- 9783712
TI  - Seminoma in a postmenopausal woman with a Y;15 translocation in peripheral blood
      lymphocytes and a t(Y;15)/45,X Turner mosaic pattern in skin fibroblasts.
AB  - We report an unusual case of a 55 year old Japanese woman with a seminoma but
      relatively normal menses. The patient was a phenotypic female with late onset
      menarche (18 years of age), who was amenorrhoeic for the first year, followed by
      menses of one to three days' slight flow with dysmenorrhoea, but an otherwise
      normal menstrual history. A typical seminoma was removed from the left adnexal
      region and an immature testis was identified separately as an associated right
      adnexal mass. Repeated karyotypic studies on peripheral blood lymphocyte cultures
      showed only 46,X,-Y,t(Y;15)(q12;p13). Cytogenetic examination of the patient's
      younger brother, who had fathered three healthy children, showed an identical
      karyotype. Mosaicism of 46,X,-Y,t(Y;15)(q12;p13)/45,X cell lines was found in
      skin samples from the patient's elbow and genital regions, although there were no
      clinical stigmata of Turner syndrome. An androgen receptor binding assay of
      cultured genital skin fibroblasts was negative. Molecular analysis using Southern
      blot hybridisation, PCR, and direct DNA sequencing showed that neither the
      patient nor her brother had a detectable deletion or other abnormalities of Y
      chromosome sequences, including the SRY (sex determining region of the Y
      chromosome) gene sequence. These findings suggest that Turner mosaicism of the
      45,X cell line may have contributed to this atypical presentation in an XY
      female, although we cannot exclude abnormalities of other genes related to sex
      differentiation.

PMID- 9783713
TI  - Further evidence for the involvement of human chromosome 6p24 in the aetiology of
      orofacial clefting.
AB  - Chromosomal translocations affecting the 6p24 region have been associated with
      orofacial clefting. Here we present a female patient with cleft palate, severe
      growth retardation, developmental delay, frontal bossing, hypertelorism,
      antimongoloid slant, bilateral ptosis, flat nasal bridge, hypoplastic nasal alae,
      protruding upper lip, microretrognathia, bilateral, low set, and posteriorly
      rotated ears, bilateral microtia, narrow ear canals, short neck, and a karyotype
      of 46,XX,t(6;9)(p24;p23). The translocation chromosomes were analysed in detail
      by FISH and the 6p24 breakpoint was mapped within 50-500 kb of other breakpoints
      associated with orofacial clefting, in agreement with the assignment of such a
      locus in 6p24. The chromosome 9 translocation breakpoint was identified to be
      between D9S156 and D9S157 in 9p23-p22, a region implicated in the 9p deletion
      syndrome.

PMID- 9783714
TI  - Discordant phenotypes and 45,X/46,X,idic(Y).
AB  - Mosaicism introduces wide variability into the clinical expression of numerical
      and unbalanced structural chromosomal abnormalities. The phenotypic range of
      variability of 45,X/46,XY mosaicism extends from Turner syndrome to mixed gonadal
      dysgenesis to normal males. The specific phenotype is primarily dependent on the
      chromosomal constitution of the developing gonad. Similar phenotypic variability
      is observed with mosaicism for 45,X and a second cell line with an abnormal sex
      chromosome. This report describes a patient with Turner syndrome and a patient
      with mixed gonadal dysgenesis who have identical karyotypes, namely
      45,X/46,X,idic(Y)(p11.2). While mosaicism alone might have accounted for the
      phenotypic differences, by PCR analysis the Turner syndrome patient was SRY and
      ZFY negative and the mixed gonadal dysgenesis patient was SRY and ZFY positive.

PMID- 9783715
TI  - Clinical features and mental development of a child with a prenatally identified
      45,XX,der(5)t(5;18) (p15;q11.2),-18 karyotype.
AB  - We present the clinical features and growth and development of a child with a
      45,XX,der(5)t(5;18) (p15;q11.2),-18 karyotype. She had microcephaly, prominent,
      posteriorly rotated ears, short palpebral fissures with an upward slant, a wide
      nasal bridge, a thin upper lip, and a short neck. In addition, she had complex
      congenital heart disease. Although there has been delay in growth and
      development, she has shown progress in both areas.

PMID- 9783716
TI  - Mesoaxial complete syndactyly and synostosis with hypoplastic thumbs: an unusual
      combination or homozygous expression of syndactyly type I?
AB  - Syndactyly type I is an autosomal dominant condition with complete or partial
      webbing between the third and fourth fingers or the second and third toes or
      both. We report here a previously undescribed phenotype of severe mesoaxial
      syndactyly and synostosis in patients born to affected parents. The
      characteristic features of these severe cases are (1) complete syndactyly and
      synostosis of the third and fourth fingers; (2) severe bone reduction in the
      proximal phalanges of the same fingers; (3) hypoplasia of the thumbs and
      halluces; (4) aplasia/hypoplasia of the middle phalanges of the second and fifth
      fingers; and (5) complete or partial soft tissue syndactyly of the toes. We
      report on three offspring with this phenotype from two different branches of a
      syndactyly type I family, suggesting that they may be homozygous for this
      condition. SSCP and linkage analysis indicated that neither HOXD13 nor other
      relevant genes in the chromosome 2q31 region was responsible for this phenotype.

PMID- 9783717
TI  - Triophthalmia and facial clefting: a case report.
AB  - We describe a Libyan boy with an unusual phenotype of multiple congenital
      anomalies, including triophthalmia, dolichocephaly, porencephaly, cleft
      lip/palate, facial asymmetry, micrognathia, and VSD. The reported phenotype is
      likely to represent a new entity of non-chromosomal syndromic triophthalmia.
      Other possibilities are discussed.

PMID- 9783718
TI  - Molecular evidence that fragile X syndrome occurs in the South African black
      population.

PMID- 9783719
TI  - High frequency of the haemochromatosis C282Y mutation in Hungary could argue
      against a Celtic origin of the mutation.

PMID- 9783720
TI  - Hypoplastic left heart in cerebrocostomandibular syndrome.

PMID- 9783721
TI  - Another dystonia.

PMID- 9783722
TI  - Metabolism of xenobiotics in the central nervous system: implications and
      challenges.
AB  - The metabolism of drugs and other xenobiotics in situ in the brain has far
      reaching implications in the pharmacological and pharmacodynamic effects of drugs
      acting on the CNS, particularly with respect to psychoactive drugs wherein a wide
      range of therapeutic response is typically seen in the patient population. An
      entirely functional cytochrome P450 (P450) monooxygenase system is known to exist
      in the rodent and human brain, wherein it is preferentially localized in the
      neuronal cells, which are the sites of action of psychoactive drugs. Further,
      bioactivation of xenobiotics, in situ, in the CNS would result in the formation
      of reactive, toxic metabolites in the neuronal cells that have limited
      regenerative capability. The presence of P450 enzymes in selective cell
      populations within distinctive regions of the brain that are affected in certain
      neurodegenerative disorders implies the potential role of P450-mediated
      bioactivation as a causative factor in the etiopathogenesis of these diseases.
      The characterization of brain-specific P450s and their regulation and
      localization within the CNS assume importance for understanding the potential
      role of these enzymes in the pathogenesis of neurodegenerative disorders and
      psychopharmacological modulation of drugs acting on the CNS.

PMID- 9783723
TI  - Opioid analgesics as noncompetitive N-methyl-D-aspartate (NMDA) antagonists.
AB  - Much evidence points to the involvement of N-methyl-D-aspartate (NMDA) receptors
      in the development and maintainance of neuropathic pain. In neuropathic pain,
      there is generally involved a presumed opioid-insensitive component, which
      apparently can be blocked by NMDA receptor antagonists. However, in order to
      obtain complete analgesia, a combination of an NMDA receptor antagonist and an
      opioid receptor agonist is needed. Recent in vitro data have demonstrated that
      methadone, ketobemidone, and dextropropoxyphene, in addition to being opioid
      receptor agonists, also are weak noncompetitive NMDA receptor antagonists.
      Clinical anecdotes suggest that the NMDA receptor antagonism of these opioids may
      play a significant role in the pharmacological action of these compounds;
      however, no clinical studies have been conducted to support this issue. In the
      present commentary, we discuss evidence for the NMDA receptor antagonism of these
      compounds and its relevance for clinical pain treatment; an overview of structure
      activity relationships for the relevant opioids as noncompetitive NMDA receptor
      antagonists also is given. It is concluded that although the finding that some
      opioids are weak noncompetitive NMDA receptor antagonists in vitro has created
      much attention among clinicians, no clinical studies have been conducted to
      evaluate the applicability of these compounds in the treatment of neuropathic
      pain conditions.

PMID- 9783724
TI  - Opposing effects of protein kinase A and C on capacitative calcium entry into HL
      60 promyelocytes.
AB  - Treatment of HL-60 cells with thapsigargin, a microsomal Ca2+/ATPase inhibitor,
      led to depletion of intracellular calcium stores followed by capacitative calcium
      entry. Stimulation of adenylyl cyclase with forskolin enhanced thapsigargin
      induced Ca2+ influx. The forskolin effect was confirmed by enhanced fluorescence
      quenching induced by Mn2+ entry into fura-2 loaded cells. 1,9-Dideoxy-forskolin,
      an inactive analog of forskolin, did not affect capacitative calcium entry. On
      the other hand, phorbol 12-myristate 13-acetate (PMA), an activator of protein
      kinase C, inhibited thapsigargin-induced Ca2+ entry. Histamine and prostaglandin
      E2 (PGE2) elevated intracellular adenosine 3':5'-cyclic monophosphate (cAMP)
      levels and enhanced the thapsigargin-induced capacitative calcium entry.
      Incubation with N-[2-(p-bromocynnamylamino)ethyl]-5-isoquinolinesulfonamide
      (H89), an inhibitor of protein kinase A (PKA), blocked the forskolin effect, and
      GF109203X, an inhibitor of protein kinase C (PKC), blocked the phorbol 12
      myristate 13-acetate effect. The results suggest that protein kinase A regulates
      capacitative calcium entry positively, but that protein kinase C regulates Ca2+
      influx negatively. Furthermore, after differentiation of HL-60 promyelocytes with
      dimethylsulfoxide to granulocytes, the inhibitory effect of phorbol 12-myristate
      13-acetate became more pronounced, whereas the stimulatory effect of
      prostaglandin E2 did not change. This result suggests that the regulation of
      capacitative calcium entry by protein kinase C and protein kinase A develops
      differently during differentiation.

PMID- 9783725
TI  - Induction of UDP-glycosyltransferase family 1 genes in rat liver: different
      patterns of mRNA expression with two inducers, 3-methylcholanthrene and beta
      naphthoflavone.
AB  - Uridine diphosphate (UDP)-glucuronosyltransferases (UGTs), presently called UDP
      glycosyltransferases, catalyse the detoxification of many toxic and carcinogenic
      compounds. Glucuronidation is also a major metabolic pathway for numerous drugs.
      The UGT1A6 gene (formerly known as UGT1*06 and UGT1A1) has been suggested to
      belong to the aryl hydrocarbon (Ah) gene battery, which consists of several genes
      encoding for drug-metabolising enzymes regulated by dioxin and other ligands of
      the Ah receptor. In this study, we analysed the localisation of UGT1A6 expression
      in rat liver by in situ hybridisation to mRNA. Two different RNA probes were
      used, one which was specific to UGT1A6 and the other against the C terminal
      sequence shared by all UGT1 genes. In this study, no UGT1A6 mRNA was detected in
      the control animals. However, other gene(s) of the UGT1 family were expressed in
      the perivenous region surrounding the central veins as detected by hybridisation
      with the probe against the common region of the UGT1 genes. Treatment with the
      lower dose (5 mg/kg) of 3-methylcholanthrene (3MC) induced expression of UGT1A6
      perivenously. Treatment with the higher dose (25 mg/kg) of 3-Methylcholanthrene
      resulted in a more panacinar expression pattern. In contrast to the perivenous
      induction observed with 3-methylcholanthrene, treatment with 15 mg/kg of beta
      naphthoflavone (BNF) resulted in strong induction in the periportal region. The
      results reveal an inducer-specific pattern of UGT1A6 expression similar to that
      demonstrated earlier for other Ah battery genes, namely CYP1A1, CYP1A2, GSTYalpha
      and ALDH3. The finding further supports the notion that common factors regulate
      the regional hepatic expression of Ah battery genes.

PMID- 9783726
TI  - Pharmacological characterisation of the D2 dopamine receptor expressed in the
      yeast Schizosaccharomyces pombe.
AB  - The rat D2(long) dopamine receptor has been expressed in the fission yeast
      Schizosaccharomyces pombe at levels of about 1 pmol/mg of protein. The
      recombinant receptor, analysed in ligand binding experiments, exhibits properties
      typical of a D2 dopamine receptor and the affinities of antagonists agree with
      values obtained for the receptor expressed in mammalian systems although the
      affinities of some antagonists are lower. Substituted benzamide antagonists show
      lower affinities in the absence of sodium ions whereas clozapine and classical
      antagonists mostly show higher affinities. Agonist binding is insensitive to the
      effects of GTP indicating lack of a stable interaction with G-proteins.

PMID- 9783727
TI  - 4-Hydroxy-17-methylincisterol, an inhibitor of DNA polymerase-alpha activity and
      the growth of human cancer cells in vitro.
AB  - An ergosterol derivative, 4-hydroxy-17-methylincisterol (HMI), was found to be an
      inhibitor of mammalian DNA polymerases in vitro. HMI inhibited the activity of
      calf thymus DNA polymerase alpha (pol. alpha). Among the polymerases tested, pol.
      alpha was the most sensitive to inhibition by HMI, and the inhibition was
      concentration dependent. The inhibitory effect of HMI on pol. alpha was almost
      the same as that shown by aphidicolin, a well-known potent pol. alpha inhibitor.
      HMI had relatively less effect on rat DNA pol. beta, human immunodeficiency virus
      type 1 reverse transcriptase (HIV-RT), and calf thymus terminal deoxynucleotidyl
      transferase (TdT) in vitro, and did not influence the activities of prokaryotic
      DNA polymerases such as Klenow Fragment of DNA polymerase I, or the DNA-metabolic
      enzyme DNase I. HMI was found to be able to prevent the growth of human cancer
      cell lines originating from patients with leukemia or various solid tumors; its
      IC50 values ranged from 7.5 to 12 microM. We also synthesized other ergosterol
      derivatives and tested them, and found that two compounds, 17-methylincisterol
      and 4-acetyl-17-methylincisterol, have similar inhibitory effects.

PMID- 9783728
TI  - Inhibition of the adherence of cholera toxin and the heat-labile enterotoxin of
      Escherichia coli to cell-surface GM1 by oligosaccharide-derivatized dendrimers.
AB  - The adherence of either cholera toxin or the heat-labile enterotoxin of
      Escherichia coli to monosialoganglioside gal(beta1-3)galNAc(beta1-4)[sialic acid
      (alpha2-3)]gal(beta1-4)glc(beta)1-ceramide (GM1) present on the surface of
      epithelial cells lining the intestine is the first step of a series that results
      in the induction of a watery diarrhea. While cholera is more severe, both can
      lead to death as a result of dehydration. To determine the potential of defined
      multivalent oligosaccharides, synthesized by the covalent attachment of multiple
      phenylisothiocyanate (PITC) derivatives of gal(beta1-3)galNAc(beta1-4)[sialic
      acid(alpha2-3)]gal(beta1-4)glc (oligo-GM1) to the arms of a poly(propylene imine)
      dendrimer, as therapeutic agents for these diseases, their ability to inhibit
      adherence of the toxins to cell surface-associated GM1 was determined. They not
      only inhibited choleragenoid (binding subunit of cholera toxin) binding to GM1
      treated NCTC-2071 cells (chemically transformed murine fibroblasts) at 5 degrees,
      but also inhibited adherence of the choleragenoid, cholera toxin, and heat-labile
      enterotoxin of E. coli to GM1-treated NCTC-2071 cells at 37 degrees. Inhibition
      was observed whether the toxin was preincubated with the oligo-GM1-PITC
      derivatized dendrimer prior to addition to cells or given just after the addition
      of the derivatized dendrimer to cells. The derivatized dendrimer had no effect on
      cell viability, as monitored by trypan blue exclusion. Blue-shifts in tryptophan
      fluorescence emission spectra maxima induced by adherence of either
      choleragenoid, cholera holotoxin, or the heat-labile enterotoxin of E. coli to
      oligo-GM1-PITC-derivatized dendrimers were similar to those induced by adherence
      to GM1 or oligo-GM1. Comparable shifts were not observed when the toxins were
      incubated with gangliosides that fail to function as receptors.

PMID- 9783729
TI  - Regulation of cytochrome P450 enzymes by aryl hydrocarbon receptor in human
      cells: CYP1A2 expression in the LS180 colon carcinoma cell line after treatment
      with 2,3,7,8-tetrachlorodibenzo-p-dioxin or 3-methylcholanthrene.
AB  - It has been difficult to study the regulation of cytochrome P4501A2 (CYP1A2)
      because expression of this enzyme is reported to be limited or absent in cell
      culture. We found that CYP1A2 can be induced significantly by 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), 3-methylcholanthrene (MC), or
      benz[a]anthracene in the human colon carcinoma cell line LS180. TCDD and MC each
      caused a dramatic elevation of CYP1A2 mRNA, as assessed by reverse transcription
      polymerase chain reaction or by northern blot analysis. TCDD also increased
      immunoreactive CYP1A2 protein and the activity of phenacetin-O-deethylase, a
      diagnostic catalytic marker for CYP1A2. The induction of CYP1A2 at all levels
      (mRNA, protein, catalytic activity) was concentration- and time-dependent: the
      EC50 for mRNA induction by TCDD = 0.5 nM, and by MC = 1.4 microM. Inducible
      CYP1A2 mRNA also was detected at lower levels in two other human cell lines, the
      hepatoma cell line HepG2 and the breast carcinoma cell line MCF-7. CYP1A1 and
      CYP1B1, additional CYP1 enzymes regulated by the aryl hydrocarbon receptor (AHR),
      also were inducible by TCDD and MC in LS180 cells; their concentration-dependent
      induction was highly correlated with induction of CYP1A2 at mRNA, protein, and
      catalytic levels. CYP1B1 was constitutively expressed and inducible in the LS180,
      MCF-7, and HepG2 cell lines as well as in the human choriocarcinoma cell line JEG
      3 and the squamous cell carcinoma line A431. CYP1A2 was neither constitutively
      expressed nor inducible in A431 or JEG-3 cells. The expression of mRNAs encoding
      the regulators of CYP1 enzymes-the AHR and its heterodimerization partner, the
      ARNT (AH receptor nuclear translocator) protein-was not altered by treatment with
      TCDD or MC. However, the cytosolic content of AHR protein and ARNT protein was
      depleted substantially following treatment with TCDD. The LS180 cell line should
      constitute a good model for further mechanistic studies on AHR-regulated CYP1A2
      expression.

PMID- 9783730
TI  - Reduction of the indoloquinone anticancer drug EO9 by purified DT-diaphorase: a
      detailed kinetic study and analysis of metabolites.
AB  - DT-diaphorase has been implicated in the activation and mechanism of cytotoxicity
      of the investigational indoloquinone anticancer drug EO9. Here, we have used a
      highly purified DT-diaphorase isolated from rat Walker tumour cells to provide
      unambiguous evidence for the ability of this enzyme to catalyze reduction of EO9
      and to provide a more detailed characterization of the reaction. Under the
      conditions used hypoxia had no effect on the initial rate of this reduction but
      did effect the nature and stability of metabolites formed. Electron spin
      resonance (ESR) spectrometry studies showed that DT-diaphorase reduced EO9 to a
      highly oxygen-sensitive metabolite that is probably the hydroquinone. In the
      presence of air, this metabolite is auto-oxidized to generate both drug- and
      oxygen-based radicals. Comproportionation:disproportionation reactions may also
      be involved in the generation of these radical species. The identification of
      these metabolites may contribute to the understanding of the molecular mechanism
      of DNA damage and cytotoxicity exerted by EO9.

PMID- 9783731
TI  - Oncocidin A1: a novel tubulin-binding drug with antitumor activity against human
      breast and ovarian carcinoma xenografts in nude mice.
AB  - We identified a structural analog of thyroid hormone, methyl-3,5-diiodo-4-(4'
      methoxyphenoxy) benzoate (Oncocidin A1), that inhibits human carcinoma cell
      proliferation and the growth of human breast (MDA MB-231) and ovarian (OVCAR-3)
      carcinoma xenografts in nude mice. This novel antitumor agent is orally
      bioavailable and well tolerated by animals. Exposure of MCF-7 and MDA MB-231
      breast carcinoma cells to Oncocidin A1 in vitro caused a cell-cycle arrest in
      prometaphase (a G2/M arrest) and apoptosis, suggesting a cytotoxic mechanism
      involving mitotic spindle function. The interaction of Oncocidin A1 with
      microtubules was demonstrated by: 1) immunofluorescence studies of microtubule
      assembly in the presence of the drug in cell-free and in cellular assays; and 2)
      in vitro binding inhibition studies involving radiolabeled Oncocidin A1 or
      colchicine and tubulin monomers. Taken together, these experiments indicate that
      Oncocidin A1 perturbs cellular microtubule assembly, possibly by binding to the
      colchicine site on tubulin. Three-dimensional structural modelling of Oncocidin
      A1 revealed that it can adopt a twisted conformation similar to that of
      combretastatin A-4, which binds to the colchicine site of tubulin. The novel
      structural features of Oncocidin A1 could guide the design of a new class of
      microtubule-binding antitumor agents having substantially reduced normal tissue
      toxicity upon oral administration.

PMID- 9783732
TI  - Effect of bryostatin 1 on taxol-induced apoptosis and cytotoxicity in human
      leukemia cells (U937).
AB  - We have examined the effects of the macrocyclic lactone protein kinase C (PKC)
      activator bryostatin 1 on taxol-induced apoptosis and inhibition of clonogenicity
      in the human monocytic leukemia cell line U937. Exposure of cells to bryostatin 1
      (10 nM; 15 hr) after (but not before) a 6-hr incubation with 0.5 microM taxol
      significantly increased apoptosis and resulted in an approximately 3 log
      reduction in clonogenicity. Cell cycle analysis revealed that the increase in
      apoptotic cells following bryostatin 1 treatment occurred primarily in the
      population undergoing taxol-mediated G2M arrest. The actions of bryostatin 1 were
      not attributable to potentiation of taxol-induced tubulin stabilization or to a
      reduction in the intracellular retention of taxol. Following exposure of cells to
      taxol, the Bcl-2 protein displayed an alteration in mobility that was not
      modified appreciably by bryostatin 1 treatment. The mobility shift in Bcl-2
      protein from cells exposed to taxol followed by bryostatin 1 was eliminated by
      treatment of lysates with the protein phosphatase 2A (PP2A); the latter effect
      was blocked by okadaic acid. Treatment of cells with taxol followed by bryostatin
      1 did not increase the amount of total Bax (compared with treatment with taxol
      alone), but did increase the amount of free Bax in the supernatant fraction.
      Finally, the ability of bryostatin 1 to potentiate taxol-induced apoptosis in
      U937 cells was mimicked closely by 2'-amino-3'-methoxyflavone (PD98059), a
      specific inhibitor of the mitogen-activated protein kinase (MAPK) kinase (MEK).
      Collectively, these findings indicate that bryostatin 1 increases the
      susceptibility of U937 cells to taxol-induced apoptosis and inhibition of
      clonogenicity. They also raise the possibility that this phenomenon may involve
      functional alterations in Bcl-2 and/or other proteins involved in regulation of
      the cell death pathway.

PMID- 9783733
TI  - Mitochondrial impairment as an early event in the process of apoptosis induced by
      glutathione depletion in neuronal cells: relevance to Parkinson's disease.
AB  - In Parkinson's disease (PD), dopaminergic cell death in the substantia nigra was
      associated with a profound glutathione (GSH) decrease and a mitochondrial
      dysfunction. The fall in GSH concentration seemed to appear before the
      mitochondrial impairment and the cellular death, suggesting that a link may exist
      between these events. The relationships between GSH depletion, reactive oxygen
      species (ROS) production, mitochondrial dysfunction and the mode of cell death in
      neuronal cells remain to be resolved and will provide important insights into the
      etiology of Parkinson's disease. An approach to determine the role of GSH in the
      mitochondrial function and in neurodegeneration was to create a selective
      depletion of GSH in a neuronal cell line in culture (NS20Y) by inhibiting its
      biosynthesis with L-buthionine-(S,R)-sulfoximine (BSO), a specific inhibitor of
      gamma-glutamylcysteine synthetase. This treatment led to a nearly complete GSH
      depletion after 24 hr and induced cellular death via an apoptotic pathway after 5
      days of BSO treatment. By using the reactive oxygen species-sensitive probe 2',7'
      dichlorofluorescin, we observed that the rapid GSH depletion was accompanied,
      early in the process, by a strong and transient intracellular increase in
      reactive oxygen species evidenced after 1 hr with BSO, culminating after 3 hr
      when the GSH level decreased to 30% of normal. GSH depletion induced a loss of
      mitochondrial function after 48 hr of BSO treatment. In particular, the
      activities of complexes I, II and IV of the respiratory chain were decreased by
      32, 70 and 65%, respectively as compared to controls. These results showed the
      crucial role of GSH for maintaining the integrity of mitochondrial function in
      neuronal cells. Oxidative stress and mitochondrial impairment, preceding DNA
      fragmentation, could be early events in the apoptotic process induced by GSH
      depletion. Our data are consistent with the hypothesis that GSH depletion could
      contribute to neuronal apoptosis in Parkinson's disease through oxidative stress
      and mitochondrial dysfunction.

PMID- 9783735
TI  - Journal evolution.

PMID- 9783734
TI  - Protection by L-2-oxothiazolidine-4-carboxylic acid of hydrogen peroxide-induced
      CD3zeta and CD16zeta chain down-regulation in human peripheral blood lymphocytes
      and lymphokine-activated killer cells.
AB  - We investigated whether L-2-oxothiazolidine-4-carboxylic acid (OTC) [in the form
      of Procysteine, kindly donated by Transcend Therapeutics] could protect
      peripheral blood lymphocytes (PBL) and lymphokine-activated killer (LAK) cells
      from CD3zeta and CD16zeta chain down-regulation induced by H2O2 produced by
      lipopolysaccharide (LPS)-activated autologous monocytes. OTC is known to enhance
      glutathione production in cells in which glutathione was depleted by reactive
      oxygen species. Our data showed that OTC induced a significant increase in
      CD3zeta and CD16zeta chain expression in peripheral blood lymphocytes and LAK
      cells, respectively, pretreated for 12 hr at 37 degrees. Moreover, OTC
      significantly protected peripheral blood lymphocytes and LAK against decreased
      zeta chain expression induced by lipopolysaccharide-activated monocytes or the
      addition of H2O2 to the culture medium. Our experiments thus suggested that
      alterations in signal-transducing molecules, such as decreased CD3zeta and
      CD16zeta expression observed in cytotoxic T lymphocytes and LAK cells in response
      to oxidative stress, could be prevented by the use of OTC.

PMID- 9783736
TI  - Mechanics of membrane fusion.

PMID- 9783737
TI  - A flattened face for membranes.

PMID- 9783738
TI  - Speeding along the protein folding highway, are we reading the signs correctly?

PMID- 9783739
TI  - Biggest virus molecular structure yet!

PMID- 9783740
TI  - Picture story. Sex and the single male X chromosome.

PMID- 9783741
TI  - Group II chaperonin in an open conformation examined by electron tomography.

PMID- 9783742
TI  - Structure of collagen.

PMID- 9783743
TI  - NMR structure of human erythropoietin and a comparison with its receptor bound
      conformation.
AB  - The solution structure of human erythropoietin (EPO) has been determined by
      nuclear magnetic resonance spectroscopy and the overall topology of the protein
      is revealed as a novel combination of features taken from both the long-chain and
      short-chain families of hematopoietic growth factors. Using the structure and
      data from mutagenesis studies we have elucidated the key physiochemical
      properties defining each of the two receptor binding sites on the EPO protein. A
      comparison of the NMR structure of the free EPO ligand to the receptor bound
      form, determined by X-ray crystallography, reveals conformational changes that
      may accompany receptor binding.

PMID- 9783744
TI  - Conformational switching in an aspartic proteinase.
AB  - The crystal structure of a catalytically inactive form of cathepsin D (CatDhi)
      has been obtained at pH 7.5. The N-terminal strand relocates by 30 A from its
      position in the interdomain beta-sheet and inserts into the active site cleft,
      effectively blocking substrate access. CatDhi has a five-stranded interdomain
      beta-sheet and resembles Intermediate 3, a hypothetical structure proposed to be
      transiently formed during proteolytic activation of the proenzyme precursor.
      Interconversion between active and inactive forms of CatD is reversible and may
      be regulated by an ionizable switch involving the carboxylate side chains of Glu
      5, Glu 180, and Asp 187. Our findings provide a structural basis for the pH
      dependent regulation of aspartic proteinase activity and suggest a novel
      mechanism for pH-dependent modulation of substrate specificity.

PMID- 9783745
TI  - Structures of HhaI methyltransferase complexed with substrates containing
      mismatches at the target base.
AB  - Three structures have been determined for complexes between HhaI
      methyltransferase (M.HhaI) and oligonucleotides containing a G:A, G:U or G:AP (AP
      = abasic or apurinic/apyrimidinic) mismatch at the target base pair. The
      mismatched adenine, uracil and abasic site are all flipped out of the DNA helix
      and located in the enzyme's active-site pocket, adopting the same conformation as
      in the flipped-out normal substrate. These results, particularly the flipped-out
      abasic deoxyribose sugar, provide insight into the mechanism of base flipping. If
      the process involves the protein pushing the base out of the helix, then the push
      must take place not on the base, but rather on the sugar-phosphate backbone. Thus
      rotation of the DNA backbone is probably the key to base flipping.

PMID- 9783746
TI  - DNA bending determines Fos-Jun heterodimer orientation.
AB  - Heterodimeric transcription factors can bind to palindromic recognition elements
      in two opposite orientations with potentially distinct effects on transcriptional
      activity. We have determined the orientation of Fos-Jun binding at different AP-1
      sites using a novel gel-based fluorescence resonance energy transfer assay. The
      orientation preference of heterodimer binding varied over a greater than 10-fold
      range. Single base pair substitutions that alter bending of flanking sequences
      reversed the orientation of heterodimer binding. Single amino acid substitutions
      that reduce the difference in DNA bending between Fos and Jun also reduced the
      orientation preference. Consequently, indirect read-out mediated by differences
      in DNA structure can contribute to the structural organization of nucleoprotein
      complexes.

PMID- 9783747
TI  - The burst phase in ribonuclease A folding and solvent dependence of the unfolded
      state.
AB  - Submillisecond burst phase signals measured in kinetic protein folding
      experiments have been widely interpreted in terms of the fast formation of
      productive folding intermediates. Experimental comparisons with non-folding
      polypeptide chains show that, for ribonuclease A and cytochrome c, these signals
      in fact reflect a shift from one biased ensemble of the unfolded state to another
      as a function of change in denaturant concentration.

PMID- 9783748
TI  - NMR solution structure of the periplasmic chaperone FimC.
AB  - The NMR structure of the 205-residue periplasmic chaperone FimC is presented.
      This protein consists of two globular domains with immunoglobulin-like folds
      connected by a 15-residue linker peptide. The relative orientation of the two
      domains is defined by hydrophobic contacts and an interdomain salt bridge. FimC
      mediates the assembly of type-1 pili, which are filamentous surface organelles of
      uropathogenic Escherichia coli strains that enable the bacteria to attach to host
      cell surfaces and persist in macrophages. The availability of the NMR structure
      of FimC provides a new basis for rational design of drugs against infections by
      uropathogenic bacteria.

PMID- 9783750
TI  - Crystal structure of botulinum neurotoxin type A and implications for toxicity.
AB  - Botulinum neurotoxin type A (BoNT/A) is the potent disease agent in botulism, a
      potential biological weapon and an effective therapeutic drug for involuntary
      muscle disorders. The crystal structure of the entire 1,285 amino acid di-chain
      neurotoxin was determined at 3.3 A resolution. The structure reveals that the
      translocation domain contains a central pair of alpha-helices 105 A long and a
      approximately 50 residue loop or belt that wraps around the catalytic domain.
      This belt partially occludes a large channel leading to a buried, negative active
      site--a feature that calls for radically different inhibitor design strategies
      from those currently used. The fold of the translocation domain suggests a
      mechanism of pore formation different from other toxins. Lastly, the toxin
      appears as a hybrid of varied structural motifs and suggests a modular assembly
      of functional subunits to yield pathogenesis.

PMID- 9783749
TI  - Millisecond Laue structures of an enzyme-product complex using photocaged
      substrate analogs.
AB  - The structure of a rate-limited product complex formed during a single initial
      round of turnover by isocitrate dehydrogenase has been determined. Photolytic
      liberation of either caged substrate or caged cofactor and Laue X-ray data
      collection were used to visualize the complex, which has a minimum half-life of
      approximately 10 milliseconds. The experiment was conducted with three different
      photoreactive compounds, each possessing a unique mechanism leading to the
      formation of the enzyme-substrate (ES) complex. Photoreaction efficiency and
      subsequent substrate affinities and binding rates in the crystal are critical
      parameters for these experiments. The structure suggests that CO2 dissociation is
      a rapid event that may help drive product formation, and that small
      conformational changes may contribute to slow product release.

PMID- 9783751
TI  - Solution structure of the cellular factor BAF responsible for protecting
      retroviral DNA from autointegration.
AB  - The solution structure of the human barrier-to-autointegration factor, BAF, a
      21,000 Mr dimer, has been solved by NMR, including extensive use of dipolar
      couplings which provide a priori long range structural information. BAF is a
      highly evolutionarily conserved DNA binding protein that is responsible for
      inhibiting autointegration of retroviral DNA, thereby promoting integration of
      retroviral DNA into the host chromosome. BAF is largely helical, and each subunit
      is composed of five helices. The dimer is elongated in shape and the dimer
      interface comprises principally hydrophobic contacts supplemented by a single
      salt bridge. Despite the absence of any sequence similarity to any other known
      protein family, the topology of helices 3-5 is similar to that of a number of DNA
      binding proteins, with helices 4 and 5 constituting a helix-turn-helix motif. A
      model for the interaction of BAF with DNA that is consistent with structural and
      mutagenesis data is proposed.

PMID- 9783752
TI  - The role of metals in catalysis by the restriction endonuclease BamHI.
AB  - Type II restriction enzymes are characterized by their remarkable specificity and
      simplicity. They require only divalent metals (such as Mg2+ or Mn2+) as cofactors
      to catalyze the hydrolysis of DNA. However, most of the structural work on
      endonucleases has been performed in the absence of metals, leaving unanswered
      questions about their mechanisms of DNA cleavage. Here we report structures of
      the endonuclease BamHI-DNA complex, determined in the presence of Mn2+ and Ca2+,
      that describe the enzyme at different stages of catalysis. Overall, the results
      support a two-metal mechanism of DNA cleavage for BamHI which is distinct from
      that of EcoRV.

PMID- 9783754
TI  - Tumour necrosis factor alpha gene polymorphisms and rheumatic diseases.

PMID- 9783753
TI  - The ternary microplasmin-staphylokinase-microplasmin complex is a proteinase
      cofactor-substrate complex in action.
AB  - The serine proteinase plasmin is the key fibrinolytic enzyme that dissolves blood
      clots and also promotes cell migration and tissue remodeling. Here, we report the
      2.65 A crystal structure of a ternary complex of microplasmin-staphylokinase
      bound to a second microplasmin. The staphylokinase 'cofactor' does not affect the
      active-site geometry of the plasmin 'enzyme', but instead modifies its subsite
      specificity by providing additional docking sites for enhanced presentation of
      the plasminogen 'substrate' to the 'enzymes's' active site. The activation loop
      of the plasmin 'substrate', cleaved in these crystals, can be reconstructed to
      show how it runs across the active site of the plasmin 'enzyme' prior to
      activation cleavage. This is the first experimental structure of a productive
      proteinase-cofactor-macromolecular substrate complex. Furthermore, it provides a
      template for the design of improved plasminogen activators and plasmin inhibitors
      with considerable therapeutical potential.

PMID- 9783755
TI  - Regaining self-control--regulation and immunotherapy.

PMID- 9783756
TI  - Joint destruction after glucocorticoids are withdrawn in early rheumatoid
      arthritis. Arthritis and Rheumatism Council Low Dose Glucocorticoid Study Group.
AB  - OBJECTIVE: Prednisolone reduced the progression of joint destruction over 2 yr in
      early, active rheumatoid arthritis. The response to discontinuation of
      prednisolone under double-blind conditions is now reported. METHODS: A
      randomized, double-blind, placebo-controlled trial of prednisolone 7.5 mg daily
      in addition to routine medication over 2 yr in 128 patients with early rheumatoid
      arthritis, using radiological progression (changes in the Larsen score) and the
      development of erosions as primary outcome measures. Study medication was blindly
      discontinued and follow-up maintained for a further year. Other assessments
      included disability, joint inflammation, pain and the acute-phase response.
      RESULTS: Similar results were obtained when all available radiographs were
      included for each year of assessment (maximum 114) and when only patients with
      radiographs at all time points were included (75 patients). In these 75, the mean
      progression in the prednisolone group was 0.21 Larsen units in year 1, 0.04 units
      in year 2 and 1.01 units in year 3 (P = 0.587, 0.913 and 0.039 for change within
      each year, respectively). The equivalent placebo group means were 2.34, 1.00 and
      1.63 Larsen units (P = 0.001, 0.111 and 0.012; difference between groups: 2.13,
      0.96 and 0.67 units, P = 0.082, 0.02 and 0.622). The percentage of hands which
      had erosions at each time point was: prednisolone group: 27.8, 29.2, 34.7 and
      39.2; placebo group: 28.2, 48.7, 59.0 and 66.5. There was little evidence for a
      flare in clinical symptoms after discontinuation of prednisolone. CONCLUSION:
      Joint destruction resumed after discontinuation of prednisolone. This
      corroborates the previously reported therapeutic effect and challenges current
      concepts of disease pathogenesis.

PMID- 9783757
TI  - Gastrointestinal tolerability of meloxicam compared to diclofenac in
      osteoarthritis patients. International MELISSA Study Group. Meloxicam Large-scale
      International Study Safety Assessment.
AB  - Although widely used, non-steroidal anti-inflammatory drugs (NSAIDs) are
      associated with a high incidence of gastrointestinal (GI) side-effects.
      Inhibition of the cyclooxygenase (COX) enzyme is the basis for both the efficacy
      and toxicity of NSAIDs. The discovery of two COX isoforms, constitutive COX-1 and
      inducible COX-2, has led to the hypothesis that selective inhibition of COX-2
      will minimize the potential for GI toxicity without compromising efficacy. The
      Meloxicam Large-scale International Study Safety Assessment (MELISSA) trial
      reported here was therefore set up to investigate the tolerability of meloxicam,
      a preferential inhibitor of COX-2, compared to diclofenac. MELISSA was a large
      scale, double-blind, randomized, international, prospective trial, conducted over
      28 days in patients with symptomatic osteoarthritis. Patients received either
      meloxicam 7.5 mg or diclofenac 100 mg slow release, the recommended doses for the
      treatment of osteoarthritis. Evaluation of the profile of adverse events was the
      main aim of the trial, together with assessment of efficacy. A total of 9323
      patients received treatment (4635 and 4688 in the meloxicam and diclofenac
      groups, respectively). Significantly fewer adverse events were reported by
      patients receiving meloxicam. This was attributable to fewer GI adverse events
      (13%) compared to diclofenac (19%; P < 0.001). Of the most common GI adverse
      events, there was significantly less dyspepsia (P < 0.001), nausea and vomiting
      (P < 0.05), abdominal pain (P < 0.001) and diarrhoea (P < 0.001) with meloxicam
      compared to diclofenac. Five patients on meloxicam experienced a perforation,
      ulcer or bleed vs seven on diclofenac (not significant). No endoscopically
      verified ulcer complication was detected in the meloxicam group compared to four
      with diclofenac. There were five patient days of hospitalization in patients on
      meloxicam compared to 121 with diclofenac. Adverse events caused withdrawal from
      the study in 254 patients receiving meloxicam (5.48%) compared to 373 (7.96%) on
      diclofenac (P < 0.001). These differences were attributable to differences in
      reported GI adverse events (3.02% on meloxicam vs 6.14% on diclofenac; P <
      0.001). Differences in efficacy, as assessed by visual analogue scales,
      consistently favoured diclofenac. In all instances, 95% confidence intervals did
      not cross zero, suggesting a statistically significant effect. However,
      differences were small (4.5-9.01% difference) and did not reach pre-determined
      levels of clinical significance. Nevertheless, significantly more patients
      discontinued meloxicam because of lack of efficacy (80 out of 4635 vs 49 out of
      4688; P < 0.01). The MELISSA trial confirms earlier studies suggesting that
      meloxicam has a significantly improved GI tolerability profile in comparison with
      other NSAIDs, including diclofenac. These results may in part reflect the
      preferential COX-2 selectivity of meloxicam, although the dose and other aspects
      of tolerability may be important. These results may provide support for the
      hypothesis that selective inhibition of COX-2 relative to COX-1 might be an
      effective approach towards improved NSAID therapy.

PMID- 9783758
TI  - Improvement in gastrointestinal tolerability of the selective cyclooxygenase
      (COX)-2 inhibitor, meloxicam, compared with piroxicam: results of the Safety and
      Efficacy Large-scale Evaluation of COX-inhibiting Therapies (SELECT) trial in
      osteoarthritis.
AB  - SELECT is a large-scale, prospective, international, multicentre, double-blind,
      double-dummy, randomized, parallel-group trial. Patients with exacerbation of
      osteoarthritis were treated with the recommended dose of meloxicam (7.5 mg) or
      piroxicam (20 mg) once daily for 28 days; 4320 patients were administered
      meloxicam and 4336 piroxicam. The incidence of adverse events was significantly
      lower in the meloxicam group (22.5%) compared with the piroxicam group (27.9%; P
      < 0.001), mainly due to the significantly lower incidence of gastrointestinal
      (GI) adverse events in the meloxicam than in the piroxicam group (10.3% vs
      15.4%,; P < 0.001), while the efficacy of both drugs was equivalent. Individual
      GI events occurred significantly less often with meloxicam than piroxicam:
      dyspepsia (3.4% vs 5.8%; P < 0.001), nausea/vomiting (2.5% vs 3.4%; P < 0.05) and
      abdominal pain (2.1% vs 3.6%; P < 0.001). There were 16 patients with
      perforations, ulcerations or bleeding (PUBs) of the upper GI tract in the
      piroxicam group compared with seven in the meloxicam group (relative risk
      piroxicam:meloxicam = 1.4). Four PUBs were complicated (perforations or
      bleedings); none of these occurred in the meloxicam group (relative risk
      piroxicam:meloxicam = 1.9). The outcome of SELECT is consistent with that of the
      large-scale clinical trial of similar design and size which compared 7.5 mg
      meloxicam with 100 mg diclofenac in patients with osteoarthritis, and with a
      previous global analysis of the safety of meloxicam. It adds further data to the
      proposed relationship between selective inhibition of cyclooxygenase-2 and
      improved GI tolerability of non-steroidal anti-inflammatory drugs.

PMID- 9783759
TI  - Oral iloprost in Raynaud's phenomenon secondary to systemic sclerosis: a
      multicentre, placebo-controlled, dose-comparison study.
AB  - OBJECTIVE: To identify the optimal dose of oral iloprost on the basis of efficacy
      and tolerability in patients with Raynaud's phenomenon secondary to systemic
      sclerosis. DESIGN: Multicentre, randomized, parallel-group comparison of two
      different doses of oral iloprost and placebo. SETTING: European university
      hospitals. PATIENTS: A total of 103 patients with Raynaud's phenomenon secondary
      to systemic sclerosis. INTERVENTION: Patients received one of three treatments
      for 6 weeks: placebo, oral iloprost 50 microg or oral iloprost 100 microg. Each
      treatment was taken twice daily, giving total daily doses of iloprost of 100 and
      200 microg. MEASUREMENTS: The frequency, total daily duration and severity of
      Raynaud's attacks were recorded in a specially designed patient diary;
      physician's global assessment and adverse events were recorded at visits to the
      clinic. Analysis was performed on an intention-to-treat population. RESULTS: A
      total of 103 patients were recruited, 89 completed the assessments throughout the
      treatment period and 82 completed an additional 6 weeks of follow-up after
      treatment. Thirty-five patients received placebo, 33 received iloprost 50 microg
      and 35 received iloprost 100 microg. The mean percentage reductions in the
      frequency, total daily duration and severity of Raynaud's attacks were
      numerically greater in the iloprost groups at the end of treatment and at the end
      of follow-up. At the end of treatment (6 weeks), there were significant treatment
      differences in the total daily duration of attacks (P = 0.03), but not in the
      severity (P = 0.07) or the frequency of attacks (P = 0.37). At the end of follow
      up (12 weeks), there were significant treatment differences in the total daily
      duration of attacks (P = 0.001) and in the severity of attacks (P = 0.007), but
      not in the frequency of attacks (P = 0.07). Percentages of patients improved at
      the end of treatment as assessed by the physician were 44% placebo, 57% iloprost
      50 microg and 64% iloprost 100 microg (not significant). Side-effects were
      reported by 80% of patients on placebo, 85% on oral iloprost 50 microg and 97% on
      oral iloprost 100 microg. Premature discontinuations of treatment in each group
      were 9, 30 and 51%, respectively, with 6, 27 and 51% being due to adverse events.
      CONCLUSION: The results on the daily duration of Raynaud's attacks suggest that
      both 50 and 100 microg oral iloprost twice daily may be effective in the
      treatment of Raynaud's phenomenon secondary to systemic sclerosis. The 50 microg
      iloprost dose was better tolerated in this patient group.

PMID- 9783760
TI  - Quantitative measurement of joint space narrowing progression in hip
      osteoarthritis: a longitudinal retrospective study of patients treated by total
      hip arthroplasty.
AB  - OBJECTIVES: To evaluate the rate of progression of radiological joint space
      narrowing (JSN) in patients operated on for hip osteoarthritis (OA) and to
      determine its predictive factors. METHODS:  STUDY DESIGN: retrospective
      longitudinal trial of 61 patients who underwent total hip arthroplasty (THA) for
      hip OA (69 operated hips). Mean follow-up 81.2 +/- 9.9 months. Collected data:
      (1) standing frontal radiographs of the pelvis from diagnosis to surgery (246
      films) for morphological evaluation and quantitative measurement of joint space
      width (JSW) (computerized reading of digitized X-rays); (2) demographic data
      (sex, age, body mass index, smoking status, professional and sporting activities,
      family history of OA); (3) clinical data (age at onset-diagnosis and THA, drug
      consumption, time from diagnosis to permanent disability, OA at other joints,
      previous THA of the contralateral hip). STATISTICS: multivariate analysis.
      RESULTS: The yearly mean narrowing (YMN) of MeanJSW was 0.43 +/- 0.43 mm/yr
      (median 0.29, range 0.03-2.55). YMN correlated inversely with joint space width
      at operation and follow-up duration, and was increased in atrophic OA (r = 0.71).
      The time between diagnosis and THA correlated with JSW at diagnosis, and was
      inversely correlated with age at onset and YMN. It was longer in patients with
      hypertrophic OA (r = 0.69). CONCLUSION: Rapid progression of JSN, older age and
      absence of osteophytes appear to be the main factors leading to THA.

PMID- 9783761
TI  - Spontaneous ambulatory activity as a quantifiable outcome measure for
      osteoarthritis of the knee.
AB  - OBJECTIVE: Quantifiable outcome measures for disabling diseases such as
      osteoarthritis (OA) of the knee are necessary in order to compare the impact of
      different interventions competing for financial resources. Current subjective and
      questionnaire data are not satisfactory for such study. In this study, we examine
      the potential of the direct measurement of ambulatory activity as such a measure.
      POPULATION: Patients with X-ray evidence of OA of the knee recruited to studies
      of anti-inflammatory agents (n = 29). Patients with OA of the knee awaiting knee
      replacement surgery (n = 28). METHODS: Comparison of various standard measures
      with total energy output data from an activity monitor. RESULTS: Spearman rho
      correlations of ambulatory energy output (number of steps x average amplitude of
      steps) correlated with other measures. Correlation with physician's opinion was
      greater than with patient's opinion (r = 0.4 and 0.2, respectively). There was no
      correlation with visual analogue pain scale or OA severity index. Correlation
      with scales of the Nottingham Health Profile questionnaire were not significant
      either for mobility (r = - 0.15) or for pain (r = - 0.13). There was, however, a
      significant correlation between poor sleep and increased activity (r = 0.34, P <
      0.05). Correlation with Kellgren X-ray grade was significant (r = - 0.45, P =
      0.01). Patients recruited to anti-inflammatory studies were 69% more active than
      those awaiting replacement surgery. CONCLUSION: The monitoring of ambulatory
      activity shows some construct and discriminant validity, and is worthy of further
      study.

PMID- 9783762
TI  - Prospective study of serum and urinary nitrate levels in patients with systemic
      lupus erythematosus.
AB  - OBJECTIVE: To study prospectively whether serum and urinary nitrate levels are
      related to lupus activity. METHODS: Fifty patients with systemic lupus
      erythematosus (SLE) were studied prospectively for 2 yr. Every 4 months, the SLE
      Disease Activity Index (SLEDAI) was administered to the patients, and blood and
      24 h urine samples were obtained; 88 healthy controls were also studied. Nitrate
      levels were measured by the Greiss method. Statistical analyses were performed
      using standard parametric and non-parametric tests, and analysis of serial
      measurements. RESULTS: Twelve patients suffered infections, 12 active nephritis
      and 17 episodes of non-renal activity. By analysis of serial measurements, serum
      and urinary nitrate levels did not correlate with SLEDAI. C-Reactive protein
      (CRP) levels, presence of infection and creatinine clearance weakly influenced
      nitrate levels. CONCLUSIONS: In SLE, serum and urinary nitrate levels do not
      parallel lupus activity. Other variables, related or not to SLE, seem to affect
      these levels.

PMID- 9783763
TI  - Shape of wear particles found in human knee joints and their relationship to
      osteoarthritis.
AB  - OBJECTIVE: To analyse and compare the shape of wear particles found in healthy
      and osteoarthritic human knee joints for monitoring the progress of
      osteoarthritis, the long-term prognosis and to evaluate therapeutic regimens.
      METHOD: Joint particles from seven patients with normal cartilage in all
      compartments of the knee joint, 12 patients with fibrillation of less than half
      the cartilage thickness (grade 1), seven patients with fibrillation of more than
      half the cartilage thickness (grade 2) and four patients with erosions down to
      bone (grade 3) were analysed. A total of 565 particles were extracted from
      synovial fluid samples by ferrography and analysed in a scanning electron
      microscope. A number of numerical descriptors, i.e. boundary fractal dimension,
      shape factor, convexity and elongation, were calculated for each particle image
      and correlated to the degree of osteoarthritis using non-parametric tests.
      RESULTS: Experiments demonstrated that there were significant differences between
      the numerical descriptors calculated for wear particles from healthy and
      osteoarthritic knee joints (P < 0.01), suggesting that the particle shape can be
      used as an indicator of the joint condition. In particular, the fractal dimension
      of the particle boundary was shown to correlate directly with the degree of
      osteoarthritis. CONCLUSION: Numerical analysis of the shape of wear particles
      found in human knee joints may provide a reliable means for the assessment of
      cartilage repair after surgical or conservative treatment of osteoarthritis.

PMID- 9783764
TI  - Comparison of clinical and self-reported diagnoses for participants on a
      community-based arthritis self-management programme.
AB  - OBJECTIVE: With the advent of community-based arthritis education programmes, it
      is important to determine the accuracy of participants' self-reported diagnoses.
      The purpose of this study was to determine the level of agreement between general
      practitioner (GP)-recorded and self-reported diagnoses of participants attending
      an Arthritis Self-Management Programme (ASMP). METHODS: Participants enrolling on
      the ASMP were asked to (a) identify their type of arthritis via a self
      administered postal questionnaire and (b) obtain a written confirmation of their
      diagnosis from their GP. The sample (n = 613) comprised mainly women (83%) with a
      mean age of 58.8 yr (S.D. 12.6) and a mean disease duration of 15.4 yr (S.D.
      12.5). RESULTS: Participants' self-reported diagnoses were confirmed by GPs in
      534 cases [87.1%, 95% confidence interval (CI): 84.4 89.8%]. Confirmed diagnoses
      were reported by 86.9% (95% CI: 83.1-90.7%) of those with osteoarthritis (OA) and
      96.1% (95% CI: 93.6 98.6%) of those with rheumatoid arthritis (RA). The
      concordance rate for all other types of arthritis combined was lower at 60.5%
      (95% CI: 49.5-71.5%). There were no significant differences with respect to age,
      gender, education, physical functioning, duration of disease and number of GP
      visits between those who correctly identified their type of arthritis and those
      who did not. CONCLUSIONS: This study suggests that the majority of RA and OA
      participants attending an arthritis education programme can correctly identify
      their specific type of arthritis.

PMID- 9783765
TI  - Interleukin-10 promoter polymorphisms in rheumatoid arthritis and Felty's
      syndrome.
AB  - OBJECTIVE: To examine whether promoter polymorphisms associated with variation in
      interleukin-10 (IL-10) production are relevant to the development of rheumatoid
      arthritis (RA) or Felty's syndrome (FS). METHODS: DNA was obtained from 44 FS
      patients, 117 RA patients and 295 controls. The promoter region between -533 and 
      1120 was amplified by polymerase chain reaction, and polymorphisms detected by
      restriction enzyme digest or sequence-specific oligonucleotide probing. RESULTS:
      We found no significant difference in allele or haplotype frequencies between the
      groups. CONCLUSION: There is no association between FS or RA and these recently
      identified IL-10 promoter polymorphisms. Other genetic or environmental factors
      could explain the alterations in IL-10 levels seen in these conditions.

PMID- 9783766
TI  - A long-term five-year randomized controlled trial of hydroxychloroquine, sodium
      aurothiomalate, auranofin and penicillamine in the treatment of patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: To compare the efficacy of hydroxychloroquine, penicillamine, sodium
      aurothiomalate and auranofin in the treatment of active rheumatoid arthritis over
      a period of 5 yr. METHOD: Five hundred and forty-one patients with definite or
      classical rheumatoid arthritis were entered into an open randomized controlled
      trial with a flexible dose regimen designed to reflect clinical practice.
      Decisions to stop treatment with any one of the disease-modifying anti-rheumatic
      drugs (DMARDs) were based on an agreed trial protocol which defined criteria for
      adverse reactions and therapeutic failure. The managing physicians' decisions
      were confirmed in a separate monitor clinic. RESULTS: The proportion of patients
      who remained on their first DMARD or who were in remission at 5 yr was 53% for
      penicillamine, 34% for sodium aurothiomalate, 31%, for auranofin and 30% for
      hydroxychloroquine (P < 0.001). In patients who stayed on their first DMARD, all
      groups showed a 30-50% improvement in C-reactive protein, erythrocyte
      sedimentation rate, Ritchie Index and joint stiffness, and a deterioration in
      their Larsen score. There was no evidence of physician bias to explain the larger
      proportion of patients remaining on penicillamine for 5 yr. CONCLUSION: Despite
      the increased popularity of sulphasalazine and inmmunosuppressives, the drugs in
      this study continue to be used worldwide. The natural history of rheumatoid
      arthritis requires long-term follow up to establish drug efficacy. Evidence is
      needed as to whether the newer regimens will prove to be more effective and safer
      in the longer term than the commonly prescribed DMARDs. The data from this trial
      will provide a reference for comparison with future studies.

PMID- 9783767
TI  - Microscopic measurement of cellular infiltration in the rheumatoid arthritis
      synovial membrane: a comparison of semiquantitative and quantitative analysis.
AB  - Microscopic measurement of inflammation in synovial tissue may be important in
      studies of clinical status, prognosis and response to treatment. The aim of this
      study was to compare quantitative microscopic analysis of inflammation with a
      semiquantitative grading system in rheumatoid arthritis (RA) synovial membrane.
      Knee synovial membrane samples from 16 patients with RA, including paired samples
      taken before and after treatment in nine patients, were immunostained with anti
      CD68 and anti-CD3 monoclonal antibodies using standard techniques. The intensity
      of macrophage and T-lymphocyte infiltration was measured both by quantitative and
      semiquantitative techniques, and the results were compared. In a cross-sectional
      comparison, both methods correlated significantly for lining layer macrophage
      infiltration, as well as sublining layer macrophage and T-cell infiltration.
      However, in some patients demonstrating a clinical response to treatment,
      semiquantitative analysis lacked sensitivity to biologically relevant changes in
      mononuclear cell infiltration. These observations have important implications for
      future studies of therapeutic modalities.

PMID- 9783768
TI  - Female sex hormones at the onset of systemic lupus erythematosus affect survival.
AB  - Female sex hormones affect susceptibility to systemic lupus erythematosus (SLE).
      To determine the effect of female sex hormones at onset of SLE on the survival of
      these patients, a retrospective survey was performed. The charts of 168 female
      SLE patients were evaluated to study the disease course, in particular the
      presence and kind of SLE criteria. Patients were classified as either belonging
      to the 'high female sex hormone at onset (HH)' or 'low female sex hormone at
      onset (LH)' group according to age at diagnosis. The statistics of the Dutch
      population, matched for age, were used to control for differences in life
      expectancy in these groups. A Cox regression model revealed that the relative
      mortality risk of HH patients vs HH controls was 4.2 times higher than the
      relative mortality risk of LH patients compared to LH controls. No differences in
      the frequency of SLE criteria between HH and LH patients were found that could
      explain the observed difference in mortality risk.

PMID- 9783769
TI  - Air oesophagogram: a frequent, but not a specific sign of oesophageal involvement
      in connective tissue diseases.
AB  - OBJECTIVE: This study investigates the role of the air oesophagogram in
      conventional chest X-rays for the diagnosis of oesophageal dysmotility in
      patients with connective tissue diseases. METHODS: Fifty-one patients with
      connective tissue diseases were studied by oesophageal manometry and lateral and
      posterior-anterior chest X-rays. The presence or absence of oesophageal air on
      chest X-rays were evaluated separately in the upper, middle and distal segment of
      the oesophagus. Forty-seven chest X-rays of patients without connective tissue
      diseases, who had undergone manometry for the evaluation of oesophagus-related
      symptoms and who had normal oesophageal function, were analysed as a control.
      RESULTS: A total of 23/51 patients with connective tissue diseases showed
      oesophageal dysfunction in manometry; 16/51 patients (31%) had air in two or more
      oesophageal segments on the lateral chest X-ray. There was a significant
      association of manometrically proven oesophageal dysmotility and air in two or
      three oesophageal segments (P < 0.05; sensitivity 48%, specificity 82%). However,
      the prevalence of an air oesophagogram showed no significant difference between
      patients with connective tissue diseases and the control group (10/47; 21%).
      CONCLUSION: The radiological sign of an air oesophagogram is neither sensitive
      nor specific enough to omit oesophageal motility studies in patients with
      connective tissue diseases.

PMID- 9783770
TI  - RheumaNet--a novel Internet-based rheumatology information network in Germany.
AB  - Knowledge transfer in medicine has traditionally been achieved through personal
      communication, the medical literature, conferences and continuous medical
      education. However, many of these methods of communication have the problem of
      currentness, and the latest knowledge is mostly transferred with a certain delay.
      In particular, chronic disease management is frequently burdened by missing,
      incomplete or delayed communication. We present the implementation of a novel,
      Internet-based information system (RheumaNet) to facilitate rapid communication
      and information transfer between the 21 German Multipurpose Arthritis Centres
      (MACs). Medical information, agendas, urgent notifications, guidelines, etc., can
      be exchanged easily via electronic mail, file transfer protocol or the World Wide
      Web. RheumaNet allows interactive on-line communication as a common platform for
      joint projects or remote consultation. It supports a set of 'core documentation'
      that has been used by all German MACs for several years. RheumaNet was used for
      the organization, on-line presentation and evaluation of the 1997 annual meeting
      of the German Rheumatology Society and is currently appointed to establish its
      public representation in the 'Web'. An on-line version of the 'Quality Assurance
      Textbook' of German rheumatology is achieved with database-derived 'dynamic' Web
      pages, allowing easy access to any information within it. Advances in the future
      include the development of on-line patient information bulletin boards, on-line
      questionnaires, the coordination of rehabilitation and educational tools for
      medical students, and professional training.

PMID- 9783771
TI  - Manchester experience in establishing a part-time MSc course in rheumatology.

PMID- 9783772
TI  - Successful treatment of gastrointestinal vasculitis due to systemic lupus
      erythematosus with intravenous pulse cyclophosphamide: a clinical case report and
      review of the literature.
AB  - Gastrointestinal vasculitis in systemic lupus erythematosus (SLE) is quite rare
      and almost always accompanied by evidence of active disease in other organs,
      although occasionally it may be the presenting feature of the disease.
      Gastrointestinal involvement in SLE may present as lupus peritonitis, non
      necrotizing pancreatitis, gastrointestinal vasculitis or surgical abdomen. Here
      we report a severe case of SLE which presented initially with fever of unknown
      origin. Severe distress, abdominal pain, the presence of occult blood in the
      stool and high acute-phase proteins were explained by a lupus peritonitis and
      intestinal vasculitis resembling inflammatory bowel disease. Whereas high-dose
      prednisone treatment did not prevent a severe relapse, we observed a sustained
      remission following i.v. cyclophosphamide pulse therapy. In the literature, only
      two similar cases are reported: one died despite a change in the therapy of a
      bowel perforation; our case was the second that improved under pulse
      cyclophosphamide. We suggest the use of cyclophosphamide after failure of
      steroids early in the course of SLE gastrointestinal vasculitis to prevent
      devastating complications.

PMID- 9783773
TI  - Re: Prolactin and systemic lupus erythematosus.

PMID- 9783774
TI  - Angiographic findings of Takayasu's arteritis in Lebanon.

PMID- 9783775
TI  - Spondylodiscitis caused by Streptococcus equisimilis.

PMID- 9783776
TI  - Joint physiology and synovial cell proliferation.

PMID- 9783777
TI  - An open study of oxpentifylline in early rheumatoid arthritis.

PMID- 9783778
TI  - Depression in rheumatoid arthritis.

PMID- 9783779
TI  - Cancer of the esophagus and cardia: does age influence treatment selection and
      surgical outcomes?
AB  - BACKGROUND: Some physicians believe that an aggressive surgical approach for the
      management of cancer of the esophagus and cardia is unwise in elderly patients
      because of allegedly higher rates of mortality and morbidity and lower rates of
      survival than those associated with younger patients. We have long advocated an
      aggressive surgical approach regardless of the patient's age and have reviewed
      our experience to determine whether age was a factor influencing treatment and
      outcomes. STUDY DESIGN: From January 1, 1970 to January 1, 1997, 505 patients
      with cancer of the esophagus or cardia underwent operations by one surgical team
      using standard surgical techniques. One hundred forty-seven patients (29.1%) were
      70 years of age or older and 358 patients (70.9%) were under 70 years of age.
      Their records and clinicopathologic features were reviewed and compared. RESULTS:
      The two groups were similar regarding the location of tumors. Tumor cell types
      were similar except for adenocarcinomas in Barrett's esophagus, which were less
      common in the older group (15.6% versus 24%; p=0.046). Surgical procedures were
      similar, as were the rates of resectability and the percentages of R0 resections.
      The hospital mortality rate was higher in the elderly patients but not
      significantly so, and the rates of major and minor complications combined were
      comparable. The differences in postresection pathologic staging were not
      significant. Satisfactory palliation of dysphagia was comparable between the
      groups, as were actuarial 5-year survival rates (24.1% of the elderly patients
      versus 22.4% of the younger patients). CONCLUSIONS: Age should not be a limiting
      factor in using an aggressive surgical approach for the management of cancer of
      the esophagus or cardia in patients aged 70 years or older. Such an approach can
      be performed as safely as in younger patients, with comparable rates of
      palliation and survival.

PMID- 9783780
TI  - Characteristics and clinical outcome of proximal-third gastric cancer.
AB  - BACKGROUND: It is generally accepted that the prognosis of patients with proximal
      gastric cancer (PGC) is worse than that of patients with more distal gastric
      cancer. STUDY DESIGN: The aim of this study was to compare the clinical features
      and outcomes of PGC with those of middle- and distal-third gastric cancers. A
      total of 646 primary gastric cancers was analyzed as a retrospective study.
      RESULTS: Proximal gastric cancer occurred in 21.8% of the 646 cancers analyzed,
      and approximately 21% of PGCs had esophageal invasion. The 5-year survival rate
      for patients with PGC was significantly lower than that of patients with more
      distal tumors. When the PGC group was divided into patients with esophageal
      invasion and without esophageal invasion, patients with esophageal invasion had
      significantly worse outcomes. When corrected for depth of invasion, lesions with
      esophageal invasion had significantly worse outcomes than those of other sites in
      T2 curative cancers. Proximal gastric cancer with esophageal invasion was
      characterized by a larger tumor, deeper penetration, and a higher incidence of
      lymph node metastasis compared with tumors in other sites, and in multivariate
      analysis of all curative cases, these variables were independent prognostic
      factors for survival. The frequency of positive proximal margins of PGC was
      higher than those of other sites. CONCLUSIONS: The relatively poor prognosis
      associated with PGC is mainly from advanced tumor stages of esophageal invasion.
      Early detection is the most important strategy to improve the survival of
      patients with PGC. In addition, aggressive lymph node dissection and chemotherapy
      for esophageal invasion should be considered even if the tumor invasion is
      moderate (T2 tumor), and a tumor-free margin is important.

PMID- 9783782
TI  - Aggressive surgical treatment of intrahepatic cholangiocarcinoma: predictors of
      outcomes.
AB  - BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common
      primary liver cancer and constitutes 10% of primary liver malignancies. Surgery
      is the optimal therapy; the majority of the patients will require extensive
      resections that are associated with significant morbidity. METHODS: We
      retrospectively studied the records of 26 patients who underwent exploratory
      laparotomy for intrahepatic cholangiocarcinoma between June 1991 and December
      1997 at the Mount Sinai Hospital. Patients with perihilar (Klatskin) tumors were
      excluded. All patients were considered resectable based on CT or MRI findings.
      Patients with positive margins or nodal invasion received adjuvant chemotherapy
      and radiation. RESULTS: Sixteen patients underwent 18 resections; in 10 patients
      the tumors were unresectable at laparotomy and only biopsy was performed. The
      mean age (62 versus 53 years) was significantly higher, and the mean total
      bilirubin level (0.71 versus 6.17 mg/dL) was significantly lower in the resected
      group (p=0.031 and 0.017, respectively). No patient with a total bilirubin over
      1.2 mg/dL was found to be resectable. Median actuarial survivals were 42.9+/-8.9
      months for resectable and 6.7+/-3.6 months for unresectable patients (p=0.005).
      Positive margins were associated with significantly shorter disease-free
      survival. But resected patients with positive margins survived significantly
      longer than those who were unresectable. Tumor size, presence of satellite
      nodules, and degree of tumor necrosis on histologic examination were significant
      predictors of outcomes. Survival among patients receiving adjuvant therapy was
      not significantly altered. CONCLUSIONS: We conclude that an aggressive surgical
      approach is warranted in patients with ICC because resection offers the only hope
      for longterm survival. Our findings emphasize the importance of achieving tumor
      free margins. Noncurative resection offers a survival advantage over no
      resection. Histologic examination of resected specimens can help select patients
      with poor prognoses.

PMID- 9783781
TI  - Treatment of hilar cholangiocarcinoma (Klatskin tumors) with hepatic resection or
      transplantation.
AB  - BACKGROUND: Because of the rarity of hilar cholangiocarcinoma, its prognostic
      risk factors have not been sufficiently analyzed. This retrospective study was
      undertaken to evaluate various pathologic risk factors which influenced survival
      after curative hepatic resection or transplantation. METHODS: Between 1981 and
      1996, 72 patients (43 males and 29 females) with hilar cholangiocarcinoma
      underwent hepatic resection (34 patients) or transplantation (38 patients) with
      curative intent. Medical records and pathologic specimens were reviewed to
      examine the various prognostic risk factors. Survival was calculated by the
      method of Kaplan-Meier using the log rank test with adjustment for the type of
      operation. Survival statistics were calculated first for each kind of treatment
      separately, and then combined for the calculation of the final significance
      value. RESULTS: Survival rates for 1, 3, and 5 years after hepatic resection were
      74%, 34%, and 9%, respectively, and those after transplantation were 60%, 32%,
      and 25%, respectively. Univariate analysis revealed that T-3, positive lymph
      nodes, positive surgical margins, and pTNM stage III and IV were statistically
      significant poor prognostic factors. Multivariate analysis revealed that pTNM
      stage 0, I, and II, negative lymph node, and negative surgical margins were
      statistically significant good prognostic factors. For the patients in pTNM stage
      0-II with negative surgical margins, 1-, 3-, and 5-year survivals were 80%, 73%,
      and 73%, respectively. For patients in pTNM stage IV-A with negative lymph nodes
      and surgical margins, 1-, 3-, and 5-year survivals were 66%, 37%, and 37%,
      respectively. CONCLUSIONS: Satisfactory longterm survivals can be obtained by
      curative surgery for hilar cholangiocarcinoma either with hepatic resection or
      liver transplantation. Redefining pTNM stage III and IV-A is proposed to better
      define prognosis.

PMID- 9783783
TI  - Epidemiology of major trauma and trauma deaths in Los Angeles County.
AB  - BACKGROUND: Our objective was to study population-based trauma-related injuries
      and deaths in the county of Los Angeles and to identify trends and progress
      towards meeting the "Year 2000 National Health Objectives." STUDY DESIGN: We did
      a retrospective study for the year 1996. Data were obtained from the Trauma
      Registry of the Emergency Medical Services of the Department of Health Services,
      and the Coroner's Department of the County of Los Angeles. Traumatic injuries and
      deaths per 100,000 of the population were calculated according to mechanism,
      race, age, and gender. RESULTS: During 1996, there were 12,136 major trauma
      admissions in the 13 trauma centers in Los Angeles County. Another 1,929 victims
      died at the scene or were certified dead at nontrauma centers and were taken to
      the Coroner's Department (total 14,065 victims). The overall major injury rate
      was 151.0 per 100,000 population and the death rate was 30.9 per 100,000. The
      trauma death rate per 100,000 population was 56.4 for African-Americans, 33.5 for
      Hispanics, 26.3 for Caucasians, and 11.6 for Asians. Homicides were the leading
      cause of traumatic deaths (45.3%) followed by traffic accidents (31.9% of
      deaths). Firearms were responsible for 3,899 major injuries or deaths (41.7 per
      100,000 population). The overall homicide rate per 100,000 population was 14.0,
      with a much higher rate for African-Americans (40.4 per 100,000) and Hispanics
      (18.7 per 100,000) than Caucasians (4.0 per 100,000) or Asians (3.4 per 100,000).
      African-American males were at very high risk for homicide (73.3 per 100,000),
      and in the age group 15 to 34 years, this problem reaches epidemic proportions
      (164.2 per 100,000). Traffic accidents accounted for 69.0 major injuries and 9.6
      deaths per 100,000 people. Males were at significantly higher risk of dying in
      traffic accidents than females. People over 60 years of age were at significantly
      higher risk of traffic-accident death than younger people, for both passenger and
      pedestrian groups (p < 0.01). Firearm-related suicides were responsible for 4.6
      deaths per 100,000 population. Caucasian males over 65 years were at much higher
      risk of suicide by penetrating trauma (29.5 per 100,000) than were Hispanics (6.3
      per 100,000), Asians (5.4 per 100,000), or African-Americans (no deaths) in the
      same gender and age group. CONCLUSIONS: Trauma remains a major health problem in
      the county of Los Angeles. Despite the significant reduction of intentional
      trauma in 1996, it still exceeds national figures and is much higher than the
      targeted "Year 2000 National Health Objectives." Aggressive prevention strategies
      need to focus on the population groups at excessive risks of injury by assault,
      traffic accidents, and suicides.

PMID- 9783784
TI  - Elevated arterial base deficit in trauma patients: a marker of impaired oxygen
      utilization.
AB  - BACKGROUND: In trauma patients, the admission value of arterial base deficit
      stratifies injury severity, predicts complications, and is correlated with
      arterial lactate concentration. In theory, elevated base deficit and lactate
      concentrations after shock are related to oxygen transport imbalance at the
      cellular level. The purpose of this study was to test the hypothesis that an
      elevated base deficit in trauma patients is indicative of impaired systemic
      oxygen utilization and portends poor outcomes. METHODS: This study was a
      retrospective analysis of a prospectively collected database. The study
      population included all patients admitted to the trauma intensive care unit at a
      Level 1 trauma center during a 12-month period who were monitored with a
      pulmonary artery catheter and serial measurements of lactate and base deficit,
      and who achieved a normal arterial lactate concentration (< 2.2 mmol/L) with
      resuscitation. The patients were divided into those who maintained a persistently
      high base deficit (> or = 4 mmol/L) and those who achieved a low base deficit (<
      4 mmol/L) during resuscitation. RESULTS: One-hundred patients (mortality 20%)
      were monitored with a pulmonary artery catheter and achieved a normal arterial
      lactate concentration. The mean age+/-SD (SEM) of the group was 37+/-17 years and
      the Injury Severity Score was 25+/-11. Subgroup analysis revealed that patients
      with a persistently high base deficit (n=26) had higher rates of multiple organ
      failure (35% versus 5%, p < 0.001) and death (50% versus 9%, p < 0.00001)
      compared with patients who achieved a low base deficit. Patients with a
      persistently high base deficit also had lower oxygen consumption (126+/-40 mL/m2
      versus 156+/-30 mL/m2, p=0.01 at 48 hours) and a lower oxygen utilization
      coefficient (0.20+/-0.05 versus 0.24+/-0.03, p=0.01 at 48 hours) compared with
      patients with a low base deficit. At 48 hours, both oxygen consumption (r=-0.44,
      [r, correlation coefficient] p=0.002) and oxygen utilization (r=-0.46, p=0.001)
      had a significant negative correlation with base deficit. CONCLUSIONS: In trauma
      patients, a persistently high arterial base deficit is associated with altered
      oxygen utilization and an increased risk of multiple organ failure and mortality.
      Serial monitoring of base deficit may be useful in assessing the adequacy of
      oxygen transport and resuscitation.

PMID- 9783785
TI  - Delayed diagnosis of blunt duodenal injury: an avoidable complication.
AB  - BACKGROUND: There is controversy about the impact on morbidity from delayed
      diagnoses of blunt hollow viscus injuries. A recent study suggested that the
      increased morbidity was primarily from delayed diagnosis of blunt duodenal injury
      (BDI). STUDY DESIGN: We studied the medical records from a 10-year period from
      June 1987 to June 1997 examining the data on 22,163 cases of blunt trauma. We
      assessed the incidence and consequences of delayed diagnoses of BDI, and
      identified preoperative factors associated with these delayed diagnoses. RESULTS:
      Thirty-five patients (0.2%) were identified in the retrospective study of the
      records from 22,163 blunt trauma patients to have sustained BDI. Of these, 25
      patients (71%) were male. Ages ranged from 1 to 58 years (mean 18.8 years), and
      the predominant mechanism was motor vehicle accident in 18 patients (51%). Seven
      patients (20%) (group I) had a diagnostic delay of > 6 hours; 28 patients (80%)
      (group II) were diagnosed in < 6 hours. Six of the seven group I patients (86%)
      were evaluated initially with CT scans, and five (83%) showed findings suggestive
      of BDI. Among the 28 group II patients, 14 (50%) underwent initial diagnostic
      peritoneal lavage (DPL), and 14 (50%) had a CT scan. In seven of the group II
      patients (50%) who were initially evaluated by CT scan, there were findings
      suggestive of BDI. Diagnostic peritoneal lavage was initially equivocal (red
      blood cell count=5,000 to 100,000) in the remaining one group I patient compared
      with three of the group II patients who had DPL. Deterioration found on physical
      examinations prompted followup CT scans in 6 group I patients (86%), and the
      scans were diagnostic for BDI in all cases. CONCLUSIONS: Blunt duodenal injury is
      an uncommon entity. Despite the presence of suggestive CT and DPL findings, the
      diagnosis was delayed in 20% of the 35 patients whose records were examined in
      the study; this delayed diagnosis was associated with increased abdominal
      complications. Patients with persistent abdominal complaints and equivocal CT or
      DPL findings should undergo laparotomy or repeat CT scan evaluations.

PMID- 9783786
TI  - Laparoscopic cholecystectomy in cirrhotic patients.
AB  - BACKGROUND: Reported mortality for open cholecystectomy in patients with
      cirrhosis ranges from 10% to 80%. Laparoscopic cholecystectomy has gained
      acceptance in the general population and has become the procedure of choice for
      symptomatic cholelithiasis. We reviewed our experience with the use of
      laparoscopic cholecystectomy in this group. STUDY DESIGN: We did a retrospective
      review of the records of 25 consecutive laparoscopic choleoystectomy procedures
      performed on cirrhotic patients from May 1992 to July 1996. RESULTS: There were
      no mortalities in our group. All procedures were completed laparoscopically. Mean
      length of stay was 1.7 days (range, 1 to 8 days). Morbidity consisted of wound
      hematomas, pneumonia, and ascites for a rate of 32%. Only patients with Child's
      Class A and Class B cirrhosis were operated on. CONCLUSIONS: Laparoscopic
      cholecystectomy can be performed safely in cirrhotic patients with well
      compensated liver function.

PMID- 9783787
TI  - Timing of video-assisted thoracoscopic debridement for pediatric empyema.
AB  - BACKGROUND: Video-assisted thoracoscopic debridement (VATD) is a new method of
      managing pediatric empyema. The purpose of this retrospective study was to
      determine the relation between the timing of VATD and its success in avoiding the
      need for open decortication. STUDY DESIGN: Twenty-one children aged 3 to 16 years
      (mean, 8 years) with symptomatic, loculated, parapneumonic empyema were treated
      with VATD at two tertiary pediatric centers between 1994 and 1997. The
      preoperative duration of symptoms, hospitalization, and previous need for
      thoracostomy drainage were compared between patients having VATD only and those
      who subsequently required a thoracotomy and decortication. Statistical analysis
      used the Wald chi-square test or Fisher's exact test with p < 0.05 considered
      significant. RESULTS: Video-assisted thoracoscopic debridement was successful in
      15 patients (group 1) and unsuccessful in six patients (group 2), who required a
      thoracotomy and decortication. Group 1 had a shorter mean duration of
      preoperative symptoms (13 versus 27 days; p=0.03), a shorter median duration of
      preoperative hospitalization (6 versus 18 days; p=0.04), and a lower incidence of
      previous thoracostomy drainage (4/15 versus 5/6; p=0.05). CONCLUSIONS: The
      technique of VATD is most likely to be successful when used within one week of
      diagnosis of a loculated parapneumonic empyema. A prospective trial comparing
      VATD with intrapleural fibrinolytic agents for the initial treatment of pediatric
      empyema is needed.

PMID- 9783788
TI  - Balloon mitral valvotomy in pregnancy: maternal and fetal outcomes.
AB  - BACKGROUND: Rheumatic mitral valve stenosis contributes to significant morbidity
      in pregnancy. Surgical commissurotomy has been performed during pregnancy in
      patients with severe mitral stenosis for several decades, but the efficacy and
      safety of percutaneous balloon mitral valvotomy (BMV) in this subset has not been
      clearly defined. STUDY DESIGN: In 1996 and 1997, 40 pregnant women aged 24+/-5
      years underwent BMV at 21+/-11 weeks of pregnancy. Special shielding was used
      during BMV to limit radiation to the fetus, except in those who were to undergo
      medical termination of pregnancy subsequently. A detailed echocardiographic
      evaluation was performed before and after BMV. After the BMV, the 29 patients in
      whom pregnancy was continued were assessed every 2 weeks for symptoms and fetal
      growth. RESULTS: The BMV procedure was successful in 39 patients with an increase
      in mitral valve area from 0.8+/-0.2 cm2 to 1.7+/-0.2 cm2 (p < 0.001) and marked
      symptomatic relief. Fluoroscopy time was 7.8+/-1.9 minutes. Eleven patients whose
      BMV was performed before 20 weeks of pregnancy, subsequently underwent medical
      termination of pregnancy uneventfully. Eighteen patients had a normal delivery,
      three underwent cesarean section for fetal distress, one had a preterm delivery,
      and there was one stillbirth. Four patients are continuing pregnancy and two are
      lost to followup. Fullterm delivery data were available in 23 babies, whose birth
      weights were 2.32+/-0.5 kg. None of these babies needed any special care and were
      healthy at discharge. CONCLUSIONS: During pregnancy, BMV by the Inoue technique
      is feasible, safe, and effective. There is marked symptomatic relief, along with
      excellent maternal and fetal outcomes.

PMID- 9783789
TI  - Magnetic resonance imaging differentiates between necrotizing and non-necrotizing
      fasciitis of the lower extremity.
AB  - BACKGROUND: Distinction between uncomplicated infective fasciitis and early
      necrotizing fasciitis can be extremely difficult without operation, yet the
      management and prognosis of both conditions depend greatly on early recognition
      and assessment of the extent of involvement. STUDY DESIGN: This was a prospective
      review of the utility of magnetic resonance imaging (MRI) in nine patients with
      suspected infective or necrotizing fasciitis treated at an academic medical
      center or a Veterans Administration hospital. RESULTS: Magnetic resonance imaging
      documented fascial inflammation, characterized by low intensity on T1-weighted
      images and high intensity on T2-weighted images, in all nine patients. Absence of
      gadolinium contrast enhancement on T1-weighted images reliably detected fascial
      necrosis in all six patients who required operative debridement. Magnetic
      resonance imaging was extremely useful in defining the extent of fasciitis and
      was more accurate in predicting necrosis or pyomyositis than was myoglobinuria or
      elevation of serum creatine kinase or lactate dehydrogenase. Operation was
      avoided in two patients without evidence of necrosis on MRI. One patient without
      evidence of necrosis, explored because of contradictory clinical findings, was
      confirmed at operation to have cellulitis without necrosis. CONCLUSIONS: Magnetic
      resonance imaging with gadolinium contrast accurately determines the presence of
      necrosis and the need for operation in patients with fasciitis of the lower
      extremity. Preoperative determination of the extent of involvement facilitates
      operative planning.

PMID- 9783790
TI  - Indications for surgical treatment of angioaccess-induced arterial "steal".
AB  - BACKGROUND: Arterial "steal" is a well-known complication following proximal
      arteriovenous (AV) fistula, but its manifestations comprise a wide spectrum of
      symptoms and there are no clear indications for those patients who need surgical
      repair. STUDY DESIGN: Among 180 consecutive AV fistulas of various
      configurations, with the brachial artery as the donor artery in all patients, 111
      patients were studied retrospectively (group A) and 69 patients were studied
      prospectively (group B). Patient records were reviewed in group A, and the
      decision for surgical correction of limb-threatening steal was based on clinical
      grounds only. In group B, all patients were followed prospectively; postoperative
      systolic blood pressure measurements were obtained, and a systolic pressure index
      (SPI) was calculated (postoperative forearm systolic pressure divided by
      contralateral forearm systolic pressure). In patients with an SPI < 0.6, nerve
      conduction studies (NCS) were performed. The decision for operation in this group
      was based on clinical examination, SPI, and NCS. RESULTS: Seven patients were
      operated on for steal-induced limb-threatening ischemia; in all seven patients,
      ischemia developed immediately after access construction. One additional patient
      with mild symptoms and deterioration in repeated NCS was considered a candidate
      for ischemic monomelic neuropathy and was successfully operated on 1 month later.
      The ligation-bypass technique was used in all patients, consisting of arterial
      ligature distal to the takeoff of the graft and short arterial bypass from a
      point proximal to the inflow of the access to a point just distal to ligation. In
      94% of the patients, some degree of distal ischemia was detected (SPI < 0.8);
      patients with SPI < 0.5 were most likely to have impaired NCS. CONCLUSIONS: Steal
      induced limb-threatening ischemia necessitating immediate surgical repair
      occurred in 3.9% (7 of 180) of our patients. The decision for surgical correction
      of steal should be based on clinical examination. Nerve conduction studies may be
      useful in patients who have an SPI value < 0.5 to detect candidates who might
      develop ischemic monomelic neuropathy. In similar patients, surgical treatment of
      steal should be offered.

PMID- 9783791
TI  - Cancer treatment in the elderly.

PMID- 9783792
TI  - Pancreatic cancer: 1998 update.

PMID- 9783793
TI  - End-of-life issues: Anencephalic infants as organ donors.

PMID- 9783794
TI  - Symposium: Genetic testing and management of the cancer patient and cancer
      families.

PMID- 9783795
TI  - Simplified technique for antegrade continence enemas for fecal retention and
      incontinence.

PMID- 9783796
TI  - Cystic duct dilation during laparoscopic transcystic common bile duct
      exploration.

PMID- 9783797
TI  - Duplex-directed thrombin injection as a method to treat femoral artery
      pseudoaneurysms.

PMID- 9783798
TI  - Delphi-panel analysis of appropriateness of high-dose therapy and bone marrow
      transplants in adults with acute lymphoblastic leukemia in first remission.
AB  - BACKGROUND: There is controversy over whether high-dose therapy and a bone marrow
      transplant is better than conventional-dose chemotherapy in adults with acute
      lymphoblastic leukemia (ALL) in first remission. This decision may depend on
      which type of donor is available: an HLA-identical sibling, an alternative donor
      transplant (HLA-matched related or unrelated people other than HLA-identical
      siblings), or autotransplant. OBJECTIVE: To determine the appropriate use of high
      dose therapy and bone marrow transplants in ALL in first remission. Develop a
      treatment algorithm. PANELISTS: Nine leukemia experts from diverse geographic
      sites and practice settings. EVIDENCE: Boolean MEDLINE searches of acute
      lymphoblastic leukemia and chemotherapy and/or transplants. CONSENSUS PROCESS: We
      used a modified Delphi-panel group judgment process. Age, white blood cell (WBC)
      count, cytogenetics and immune type were permuted to define 48 clinical settings.
      Each panelist rated appropriateness of high-dose therapy and a transplant versus
      conventional-dose chemotherapy on a 9-point ordinal scale (1, most inappropriate;
      9, most appropriate) considering three types of donors: (1) HLA-identical
      siblings; (2) alternative donors; and (3) autotransplants. An appropriateness
      index was developed based on median rating and amount of disagreement.
      Relationship of appropriateness indices to the permuted clinical variables was
      considered by analysis of variance and recursive partitioning. Preference between
      donor types was analyzed by comparing mean appropriateness indices of comparable
      settings and a treatment algorithm was developed. CONCLUSIONS: In people with an
      HLA-identical sibling donor, transplants were rated appropriate in those with
      unfavorable cytogenetics and uncertain in all other settings. An HLA-identical
      sibling donor was always preferred to an alternative donor or autotransplant. In
      people without an HLA-identical sibling but with an alternative donor, this type
      of transplant was rated appropriate in those with unfavorable cytogenetics.
      However, an autotransplant was preferred over an alternative donor transplant in
      all other settings where a transplant was rated uncertain. In people without an
      HLA-identical sibling or alternative donor, autotransplants were rated uncertain
      in all settings except in those with not unfavorable cytogenetics, WBC < 100 x
      10(9) l(-1) and T- or pre-B-cell type where they were rated inappropriate.

PMID- 9783799
TI  - S-phase induction by interleukin-6 followed by chemotherapy in patients with
      refractory multiple myeloma.
AB  - The plasma cell labeling index (PCLI) in patients with multiple myeloma (MM) is
      relatively low and this has been associated with the low rate of remission
      following chemotherapy. Interleukin-6 (IL-6) has been demonstrated to be a major
      growth factor of myeloma cells. In order to increase the S-phase proportion of
      myeloma cells, which might increase the sensitivity to chemotherapy, we gave rhIL
      6 followed by chemotherapy to 15 myeloma patients with refractory disease. A
      total of 25 treatment cycles were administered since ten patients had two cycles.
      The rhIL-6 dose was 2.5 (n = 3), 5.0 (n = 6) and 10.0 microg/kg (n = 6) by
      subcutaneous injection once daily for 5 days and chemotherapy was administered on
      the last day of rhIL-6 injection. The effect of rhIL-6 treatment on labeling
      index (LI) was heterogeneous, but no statistically significant change was noted
      for this particular group as a whole. In two patients an increase (mean 7.7%) in
      LI of mononuclear bone marrow cells during the rhIL-6 treatment was demonstrated
      and in one patient a decrease of 2.8% was seen. Assessment of PCLI demonstrated
      an increase of 2.9% in one out of six patients and a decrease of 1.9% in one out
      of six patients. None of the 15 patients achieved remission according to standard
      criteria. During the rhIL-6 treatment, 14 of the 15 patients developed mild
      constitutional adverse events (AE) well known in patients treated with IL-6, and
      none of the AE in the subsequent chemotherapy phase were related to IL-6. In
      conclusion, our study demonstrated that rhIL-6 can be administered safely to
      patients with refractory MM, but the cell cycle recruitment approach was not
      sufficiently effective to be of clinical value.

PMID- 9783800
TI  - The role of thiotepa in autologous bone marrow transplantation for acute
      leukemia.
AB  - Post-transplant leukemic relapse remains the major problem following autologous
      bone marrow transplantation (ABMT). One possible approach to reducing the relapse
      rate is to intensify pre-transplant conditioning. Thiotepa (TTP) is an alkylating
      agent that has been used mainly in breast and ovarian cancer with 20-50% response
      rates. This report presents our results on 33 patients with acute leukemia (acute
      myeloblastic leukemia (AML) 27 patients, acute lymphoblastic leukemia (ALL) six
      patients) who underwent ABMT following conditioning with busulfan (BU), 4 mg/kg x
      4 days (days -8 to -5), TTP 5 mg/kg x 2 days (days -4, -3) and cyclophosphamide
      (CY) 60 mg/kg x 2 days (days -2, -1). Of the 33 patients, 22 were males and 11
      females, of median age 24 (1-55) years. Twenty-eight patients were transplanted
      in complete remission (AML 26; ALL 2) while 5 (AML 1; ALL 4) were in early
      relapse. Twenty-nine additional AML patients (15 females, 14 males) of median age
      22 (2-48) years, who underwent ABMT following a standard BU-CY conditioning
      regimen (25 in complete remission and four in relapse) served as historical
      controls. There were no significant differences between the study and control
      groups with respect to patient age, sex, diagnosis, stage of disease, FAB
      classification, and prior chemotherapy, at ABMT. Overall survival, disease free
      survival (DFS), and relapse rate at 72 months were 33, 33 and 61%, respectively,
      for the study group, and 38, 34.5 and 52%, respectively, for the historical
      controls. Engraftment and transplant related toxicity also did not differ
      significantly in the two groups. In conclusion, TTP appears to have made no
      substantial improvement to the outcome of ABMT for acute leukemia.

PMID- 9783801
TI  - The MACOP-B and VACOP-B combination chemotherapy for young patients with
      intermediate-grade non-Hodgkin's lymphoma.
AB  - Since the early 1970s, three generations of combination chemotherapy for
      intermediate-grade non-Hodgkin's lymphomas (NHL) have been developed. One of the
      third-generation regimens is MACOP-B (methotrexate, doxorubicin,
      cyclophosphamide, vincristine, prednisone, and bleomycin). The VACOP-B regimen is
      a modification of MACOP-B in which methotrexate is omitted and etoposide is
      added. This study assesses treatment outcome using the MACOP-B and VACOP-B
      combination chemotherapy in a population of young patients with intermediate
      grade NHL treated in a single tertiary hematological center. The files of 45
      patients aged 18-55 who were diagnosed as having intermediate-grade NHL (working
      formulation types F-H) and treated between January 1986 and March 1994 were
      reviewed. Treatment response, overall survival, disease-free survival and
      treatment toxicity were determined. The predictive value of the age-adjusted
      international prognostic index was also assessed. Median follow-up was 80 months
      in the MACOP-B group and 29 months in the VACOP-B group. The complete response
      rate was 71% (95% confidence interval CI: 58-84), 4-year overall survival was 74
      +/- 7% and 4-year disease-free survival was 79 +/- 8%. No toxicity-related deaths
      were observed. The main adverse effects were WHO grade 3 or 4 neutropenia (51%),
      anemia (24%) and mucositis (20%). Only the CR rate was correlated with the Age
      Adjusted International Prognostic Index. Mean relative dose intensity was high
      (95.7%, 95%) CI: 91.7-99.7) and had no correlation with treatment outcome. The
      MACOP-B and VACOP-B combination chemotherapy regimens were found to be effective
      and minimally toxic for young patients up to 55 years old with intermediate-grade
      NHL.

PMID- 9783802
TI  - Mutational analysis of N-RAS and GAP-related domain of the neurofibromatosis type
      1 gene in chronic myelogenous leukemia.
AB  - RAS mutations can be detected in a variable number of patients with
      myeloproliferative disorders such as myelodysplastic syndromes and acute myeloid
      leukemia, but are rare events in chronic myelogenous leukemia in chronic phase.
      However, there is good evidence supporting the involvement of RAS signalling
      pathway in CML and this could be due to alterations in RAS activity regulatory
      proteins. The neurofibromatosis (NF1) gene down-regulates the RAS signal
      transduction pathway through the inhibitory function of its GAP-related domain
      (GRD) on RAS protein. The loss or alteration of neurofibromin (the NF1 protein)
      may produce a disfunction similar to point mutations in the RAS gene resulting in
      the permanent stimulation of the RAS signal transduction pathway. Mutations
      involving the GRD region of the NF1 gene (GRD-NF1) have been described in a
      variety of tumors such as colon carcinoma and astrocytoma. Germline mutations and
      deletions in the NF1 gene, as seen in neurofibromatosis type 1, are also
      associated with certain myeloid disorders. In the present work, we sought to
      identify mutations in the codons 12/13 and 61 of RAS gene and in the Lys-1423
      codon of GRD-NF1, which are well known hot spots in these genes, in a group of 36
      adults and ten children with chronic myelogenous leukemia in chronic phase and
      blast crisis. Using the PCR-SSCP and the allele-specific restriction assay (ASRA)
      techniques, we were not able to observe any RAS or NF1 detectable mutation. These
      findings suggest that RAS and GRD-NF1 mutations are not involved either in
      chronic phase or in the progression to blast crisis in chronic myelogenous
      leukemia in adults and children.

PMID- 9783803
TI  - Revealing some oncofetal antigens in peripheral blood mononuclear cells of donors
      and patients with B-chronic lymphocytic leukemia.
AB  - Eidelman et al. showed that the expression of functional carcinoembryonic antigen
      (CEA) on the surface of cells can block terminal differentiation and maintain
      their proliferative capabilities. This led us to analyze the expression of CEA,
      trophoblast-specific beta-1-glycoprotein (TSG) and embryonic prealbumin-1 (EPA)
      in peripheral blood mononuclear cells (PBMs) isolated from healthy donors and
      patients with B-chronic lymphocytic leukemia (B-CLL). We demonstrated that the
      PBMs of patients with B-CLL differed from PBMs of healthy donors by having
      greater numbers of CEA-, EPA- and TSG-positive cells.

PMID- 9783804
TI  - A rare variant translocation t(3;8)(q29;q22) without AML1/ETO fusion transcript
      in a case of oligoblastic leukemia.
AB  - A 43-year-old man with oligoblastic leukemia and t(3;8) variant translocation is
      reported. At first he was classified as refractory anemia with excess of blasts
      in transformation according to the FAB criteria for myelodysplastic syndrome.
      Remission was obtained after intensive chemotherapy. After 8 months, a relapse
      occurred as overt M2 AML. At presentation chromosome study of bone marrow cells
      using R- and G-bandings revealed 45,X, -Y,t(3;8)(q29;q22) in 35 of the 42
      metaphases analyzed and 46,XY,t(3;8) in one metaphase in addition to normal
      karyotype in the other six metaphases. However, RT-PCR assay showed no AML1/ETO
      fusion transcript. At relapse, a karyotype of 46, XY,t(3;8), deletion(4)(p14),
      add(7)(q32) was observed in all abnormal cells indicating a clonal karyotypic
      evolution. We believed that this case should be diagnosed as an early form of M2
      AML initially. It may be the first case of oligoblastic leukemia with t(3;8)
      variant translocation. Further study is needed to elucidate its molecular entity.

PMID- 9783805
TI  - Drug resistance of secondary acute myeloid leukemia with megakaryoblastic
      features and p190 BCR-ABL rearrangement.
AB  - A 46-year-old female presented with acute myeloid leukemia during complete
      remission of multiple myeloma after extensive treatment with alkylating agents.
      Leukemic blasts expressed CD34, platelet esterase and gp IIIa. RT-PCR analyses of
      peripheral blood cells detected a p190 type BCR-ABL rearrangement and high levels
      of MDR1. The patient expired during neutropenia shortly after induction
      chemotherapy. Autopsy revealed persistent blasts in the bone marrow, spleen and
      liver. 'Secondary' acute myeloid leukemia with megakaryoblastic features and p190
      type BCR-ABL rearrangement has not previously been reported. The possibility that
      the combination of a BCR-ABL rearrangement with overexpression of MDR1 may have
      contributed to the treatment-refractory course is discussed.

PMID- 9783807
TI  - Identification of an upstream enhancer containing an AML1 site in the human
      myeloperoxidase (MPO) gene.
AB  - Myeloperoxidase (MPO) is an important antibacterial enzyme found only in
      granulocytes and monocytes. The human MPO gene is transcribed early during
      myelogenesis but MPO RNA synthesis ceases at the end of the promyelocyte stage of
      myeloid maturation. We recently identified a basal MPO promoter and several
      adjacent cis-elements in the proximal 5'-flanking region of this gene.
      Transfection studies using constructs containing several kb of 5'-flanking MPO
      DNA revealed the presence of a DNA segment located between bp (base pair) -4200
      and bp -3800 with enhancer activity for the endogenous basal MPO promoter.
      Deletion studies revealed the core enhancer activity to lie between bp -4100 and
      bp -3844. The percentage enhancement of promoter activity is greater in MPO
      expressing myeloid cells than in MPO-non-expressing myeloid cells or non-myeloid
      cells. Furthermore. the enhancer confers TPA- or DMSO-responsiveness upon either
      endogenous or exogenous promoters. DNase I footprinting and transfection
      experiments identified an AML1 site as a functionally important element within
      the enhancer. Gelshift competition and supershift experiments demonstrated the
      binding of the alpha subunit of the transcription factor AML1 to this site in HL
      60 cells. This distal enhancer appears likely to play an important role in the
      control of MPO transcription during myeloid differentiation.

PMID- 9783806
TI  - Expression profiles of I and sialosyl-I antigens on blood cells: the sialosyl-I
      antigen is expressed along the monocytic differentiation.
AB  - Expression of I and sialosyl-I antigens was examined using specific monoclonal
      antibodies. The anti-I antibody C6 reacted with monocytes (24%), T cells (55%), B
      cells (80%) but not with neutrophils (4%), bone marrow (BM) CD34+ cells (2%) or
      mobilized peripheral blood (PB) CD34+ cells (1%). The anti-sialosyl-I antibody
      NUH2 reacted with monocytes (38%) and BM CD34+ cells (41%) but not with T cells
      (2%), B cells (0%) or neutrophils (1%) and it hardly reacted with mobilized PB
      CD34+ cells (8%). Flow cytometric analyses of CD34+ cells enriched from BM showed
      that most of the sialosyl-I cells expressed CD13, CD33, CD117, and HLA-DR.
      Sialosyl-I+ CD34+ cells isolated from BM produced a large number of granulocyte
      macrophage colonies and macrophage colonies. Therefore, sialosyl-I+ CD34+ cells
      are suggested to be colony-forming units granulocyte-macrophage (CFU-GM) and
      colony-forming units macrophage (CFU-M). BM CD34+ cells cultured in medium
      containing cytokines produced I+ CD14+ monoblasts and sialosyl-I+ CD14+
      monoblasts. Leukemic cells from patients with acute myeloid leukemia were I
      negative (32/32) and sialosyl-I-positive (one/32). Leukemic cells from patients
      with acute lymphoid leukemia were I-positive (four/ten) and sialosyl-I-negative
      (ten/ten). These results indicate that (1) the I antigen is broadly expressed by
      monoblasts, monocytes, lymphocytes, and leukemic lymphoblasts, and (2) the
      sialosyl-I antigen is expressed along the normal differentiation of CFU-GM to
      monocytes.

PMID- 9783808
TI  - Characterization of cytotoxicity induced by sphingolipids in multidrug-resistant
      leukemia cells.
AB  - Certain sphingolipids (SLs) exert fundamental roles in differentiative, growth
      inhibitory and apoptotic pathways induced by a number of agents in leukemia
      cells. Multidrug-resistance (MDR) is a major cause of therapeutic failure in
      leukemia. SLs are among the diverse substrates for the MDR p-170 glycoprotein
      drug-efflux pump. We tested the hypothesis that expression of MDR would thereby
      block the cytotoxicity induced by the SLs sphingosine, sphinganine and N-hexanoyl
      sphingosine. An MDR-expressing subline of murine P388 leukemia cells demonstrated
      an ED50 value > or = 2 log10 higher than the parental line in response to
      doxorubicin. In contrast, the ED50 values for each of the SLs were only
      approximately 1.5 to two-fold higher in the MDR line than in the parental;
      induction of DNA damage by SLs was comparable or actually greater in MDR compared
      to parental cells. Therefore, expression of MDR does not significantly affect the
      cytotoxic function of these SLs, nor do these SLs likely contribute to MDR.

PMID- 9783809
TI  - Retinoic acid differentially regulates interleukin-1beta and interleukin-1
      receptor antagonist production by human alveolar macrophages.
AB  - Mechanism in the pathogenesis of acute respiratory distress syndrome which is the
      clinical feature of pulmonary involvement in retinoic acid (RA) syndrome has been
      investigated. Pulmonary infiltration of matured neutrophils and leukemic cells is
      thought to be associated with the pathogenesis of pulmonary involvement in RA
      syndrome; however. Little is known about the mechanism in pulmonary infiltration
      of these cells. In the present study, we examined the effect of RA on IL-1beta
      and IL-1ra production by human alveolar macrophages in order to clarify the
      mechanism in pulmonary infiltration of neutrophils, since IL-1 has been shown to
      initiate neutrophil recruitment into the lung through up-regulated expression of
      adhesion molecules on vascular endothelium. RA enhanced IL-1beta and inhibited IL
      1ra production by 4beta phorbol 12beta-myristate-13alpha acetate (PMA)- and
      lipopolysaccharide (LPS)-stimulated human alveolar macrophages. These results
      show that RA differentially regulates IL-1beta and IL-1ra production by alveolar
      macrophages and indicate that an imbalanced production between IL-1beta and IL
      1ra may contribute to initiating neutrophil recruitment into the lung through up
      regulated expression of adhesion molecules.

PMID- 9783810
TI  - Effects of two sex steroids (17beta estradiol and testosterone) on proliferation
      and clonal growth of the human monoblastic leukemia cell line, U937.
AB  - We investigated the effects of two sex steroids (17beta estradiol and
      testosterone) on five human leukemia cell lines. We observed a statistically
      significant inhibition of proliferation, dose and time dependent, of the human
      monoblastic leukemia cell line U937. This inhibition was associated with a dose
      dependent decrease in the number of CFU-blasts in clonogenic cultures. Cytostatic
      effect was obtained with doses of 5 microM for estrogen and 10 microM for
      androgen and was not due to a non-specific cytotoxic effect, some cell viability
      remained high (> 90%) even after 6 days of incubation. More accurately, we
      demonstrated that growth inhibition was associated with a cell cycle arrest, U937
      cells accumulating in G2/M phase. This blockade was dose related with a maximum
      number of cells accumulating at day 4. Sensitivity of these cells to an S-phase
      specific agent (hydroxyurea) was not increased, suggesting that these cells were
      blocked in G2/M and did not undergo mitosis. Expression in U937 cells of high
      affinity nuclear receptors for estrogen and androgen was negative which was in
      favour of a type II estrogen binding site, mediated mechanism. Moreover, a small
      fraction of these cells underwent apoptosis or differentiation with about 12%
      apoptotic cells and a significant increase (more than 30%) of two myelomonocytic
      markers (CD13 and CD64). These results demonstrate that the proliferation of some
      leukemic cells may be inhibited by micromolar concentrations of sex steroids,
      independently of nuclear receptor expression. The main mechanism seems to be a
      block in cell cycle associated with modulation of apoptosis and differentiation.
      It provided additional evidence for the potential value of sex steroids and their
      analogues in the treatment of leukemias.

PMID- 9783811
TI  - Further characterization of cyclophosphamide resistance: expression of CD95 and
      of bcl-2 in a CML cell line.
AB  - Drug resistance is a common cause of treatment failure in oncology. In addition
      to the resistance caused by over-expression of p-glycoprotein and similar
      molecules other mechanisms are involved in the selection or induction of drug
      resistant tumor cells. In this study, we characterized a CML cell line made
      resistant to cyclophosphamide (KBM7-B5-1803) further for the expression of
      apoptosis promoting and inhibiting molecules. We found that KBM7-B5-1803 has a 3
      4-fold over-expression of the receptor CD95 (Fas/Apo-1) compared with the parent
      line. The regulation of CD95 by cytokines was comparable to other types of cells.
      Despite the inducibility and over-expression of CD95, CD95 failed to trigger
      apoptosis in both the parent and the drug resistant line. The drug resistant line
      has a particular pattern of the expression of bcl-2 family members: bcl-2 protein
      and message were expressed to a similar extent, however, compared with the parent
      line, the message for bclx short was decreased. P-glycoprotein was not expressed
      in either cell line. Taken together we show here in a leukemia cell line that the
      phenotype of cyclophosphamide resistance is associated with a particular pattern
      of apoptosis-related molecules.

PMID- 9783812
TI  - Physiological stability of preterm infants during magnetic resonance imaging.
AB  - AIM: This study looked for evidence of physiological disturbance in preterm
      infants undergoing magnetic resonance imaging (MRI). METHODS: Intensive care was
      continued, as appropriate, throughout scanning in each infant. The heart rate,
      oxygen saturation (SaO2), temperature and mean arterial blood pressure (BP) was
      monitored during MRI in preterm infants, median gestational age at birth 27
      (range 23-32) weeks and median postnatal age at initial MRI, 3 days (range 1-42).
      The acoustic noise level during imaging was also measured. RESULTS: 2087 min of
      data were obtained from 39 examinations in 23 infants. The median heart rate was
      159 and no bradycardia < 100 or tachycardia > 200 bpm occurred. Although 42
      episodes of desaturation < 90% were detected only three were < 80, and these
      occurred in one infant due to endotracheal tube blockage. The median axillary
      temperature was 36.9 degrees C (range 35.7-37.8) and median BP (n = 6) was 37
      mmHg (24-48). The ambient noise level in the MR system during scanning was 67-72
      dBA. CONCLUSION: In preterm infants who required intensive care during scanning,
      MRI could be performed without major physiological instability.

PMID- 9783813
TI  - Effect of experimentally induced urethral obstruction and surgical decompression
      in utero on renal development and function in rabbits.
AB  - To investigate the effect of urethral obstruction during late fetal life on renal
      development and function, we developed a rabbit fetal model of obstructive
      nephropathy to examine the pathological and biochemical consequences of urethral
      obstruction and beneficial effects of early surgical decompression. Animals were
      divided into four groups, i.e., obstructed, early decompressed, late
      decompressed, and control. Fetal renal development was evaluated by histological
      examination and counting the number of glomeruli in the four groups. The number
      of renal glomeruli correlated with gestational age in the normal fetus (r = 0.90,
      P < 0.0001). Urethral ligation on gestational day 25 (full-term, 31 days)
      resulted in thinning of the renal cortex and significantly decreased the number
      of renal glomeruli. The concentration of urinary microalbumin was higher when
      urethral obstruction was maintained for 3 days than 1 day after urethral
      obstruction, although urinary beta2- microglobulin, Na, Cl, and osmotic pressure
      did not change during this period. Decompression of urethral obstruction 1 day
      after induction of urethral obstruction resulted in improvement in the severity
      glomerular hypoplasia compared with late decompression (P < 0.01). Our results
      suggest that the rabbit fetal model simulates fetal urethral obstruction in
      humans, and indicates that early surgical decompression may be effective in
      restoration of normal renal function.

PMID- 9783814
TI  - State transitions in uncomplicated pregnancies after term.
AB  - A behavioural state transition is the time interval between two different
      behavioural states. In low-risk fetuses, the fetal heart rate pattern (FHRP) is
      the first variable to change in transitions from 1F to 2F ('non-REM-sleep' to
      'REM-sleep') and the last variable to change in transitions from 2F to 1F. This
      is not the case in IUGR (intra-uterine growth retardation), and absence of a
      specific order in which behavioural variables are changing might be an indication
      for a (mild) disturbance of the fetal central nervous system (CNS). We
      investigated whether state transitions in twelve low risk term fetuses (39-41
      weeks post menstrual age, PMA; control group) differ from those in twelve
      uncomplicated pregnancies > 41 weeks PMA (study group). All subjects underwent
      one behavioural study in which fetal heart rate pattern, eye and body movements
      were recorded simultaneously. We recorded 23 transitions from 1F to 2F and 20
      from 2F to 1F. Median (range) duration for transitions from 1F to 2F was 85 (10
      180) s in the study group, and 60 (10-180) s in the control group. Transitions
      from 2F to 1F lasted 80 (10-140) and 60 (30-100) s, respectively. In both groups,
      the FHRP was the first variable to change in transitions from 1F to 2F, however,
      in transitions from 2F to 1F, no specific order in change of variables could be
      demonstrated. We conclude that the study of transitions does not distinguish
      between the term and after term fetuses under optimal conditions. Whether or not
      the analysis of state transitions can be used to distinguish 'normal' from
      'abnormal' fetuses and detect the fetus at risk after term awaits further study.

PMID- 9783815
TI  - Immaturity of electrophysiological response of the neonatal auditory brainstem to
      high repetition rates of click stimulation.
AB  - Changes in brainstem auditory evoked response (BAER) with varying stimulus
      repetition primarily represent neural processes concerning the efficacy of
      synaptic transmission in the brainstem auditory pathway. In this study the BAER
      to different rates of clicks was recorded from 16 term neonates. The results were
      compared with those from 16 adults to examine whether the degree of maturation of
      synaptic transmission of the neonatal brainstem auditory pathway parallels that
      of general function of the pathway. All BAER wave latencies and interpeak
      intervals increased linearly and wave amplitudes reduced with increasing click
      rate. The absolute rate-dependent changes in BAER measures were much greater in
      the neonates than in the adults, reflecting a significant immaturity in the
      efficacy of synaptic transmission in the neonatal auditory brainstem and in the
      ability of the neonatal brainstem to process rapid acoustic stimulation. When the
      data obtained at higher click rates at various age groups were analyzed as
      percentages, using the BAER measurements at conventionally used slow rate (21/s)
      of clicks as the denominators, the changing rates (%), or relative changes, of
      most BAER measures at higher rates in the neonates were still greater than those
      in the adults. Therefore, the rate-dependent BAER changes in the neonates are
      relatively less mature than general aspects of the BAER, reflected by the BAER
      elicited with conventionally used slow rates of clicks. These findings suggest
      that synaptic efficacy in the neonatal brainstem auditory pathway is relatively
      less mature than general function of the pathway and thus may be more susceptible
      to unfavourable perinatal conditions.

PMID- 9783816
TI  - Cardiorespiratory stability of premature boys and girls during kangaroo care.
AB  - The objective of the investigation was to study the stability of the
      cardiorespiratory system of 20 premature boys and girls during maternal kangaroo
      care (KC) and in the incubator. Stability of heart rate, respiration and oxygen
      saturation was compared in a pretest-test-posttest design by means of a stability
      score. The three stability items and the total stability did not change
      significantly during the three conditions. In some individuals the stability
      either increased or decreased markedly during Kangaroo Care. The boys showed
      significantly less cardiorespiratory stability both during kangaroo care and in
      the incubator compared to the girls.

PMID- 9783817
TI  - Plasma vitamin A levels in the very low birthweight infant--relationship to
      respiratory outcome.
AB  - OBJECTIVE: To examine the association between plasma vitamin A levels and outcome
      measures in very low birthweight (VLBW) infants, including meta-analysis of all
      observational studies. DESIGN: A prospective observational longitudinal study of
      plasma vitamin A levels measured in the cord blood; maternal blood in the first
      48 h after delivery; and the infants' blood at 48 h, 7 days and 28 days of age
      and correlated with antenatal and postnatal events. A meta-analysis of all
      published observational studies on the association of vitamin A with respiratory
      outcome in the VLBW infant was undertaken. PATIENTS: Fifty-seven infants (88% of
      all eligible) VLBW infants (< 1500 g) admitted from January through October 1993
      to one of two regional neonatal intensive care units in the South Island of New
      Zealand. RESULTS: Exposure to antenatal steroids led to a significant increase in
      infant cord plasma vitamin A levels (P = 0.003), but no influence on infant
      plasma vitamin A levels at any other time. Exposure to postnatal steroids
      produced a significant rise in infant plasma vitamin A levels between 7 and 28
      days (P = 0.008). After controlling for gestational age, antenatal and postnatal
      steroid exposure, low vitamin A levels at 48 h increased the risk of developing
      chronic lung disease (odds ratio for 50 microg/l decrease: 2.04, 95% CI 1.19
      5.77) and bronchopulmonary dysplasia (odds ratio 1.96, 95% CI 1.14-6.87). On
      combining our results in meta-analysis with those of other published prospective
      observational studies, infants with chronic lung disease had lower plasma vitamin
      A levels at all times. CONCLUSIONS: Our results support an association between
      low plasma vitamin A levels and adverse outcome in the VLBW infant.

PMID- 9783818
TI  - Intra-individual stability of rate of gross motor development in full-term
      infants.
AB  - The purpose of this study was to evaluate the intra-individual stability of gross
      motor scores obtained by normally developing full-term infants on the Alberta
      Infant Motor Scale (AIMS). The gross motor skills of 47 infants were assessed
      monthly in their homes by pairs of physical therapists. Infants were followed
      from two weeks of age until they achieved independent walking. A developmental
      pediatrician assessed each infant at 18 months of age, and classified the
      infant's gross motor skills as normal, suspicious or abnormal. Only the data of
      infants receiving a normal classification at 18 months were included in the
      analyses (n = 45). Individual infants' percentile ranks varied considerably from
      month to month, with no systematic pattern of change noted across infants. As a
      group, the mean percentile range over 13 assessments was 66.78 (S.D. 13.47).
      Fourteen infants (31.1%) received a score below the 10th percentile on at least
      one occasion. The results suggest that normally developing infants are not stable
      in the rate of emergence of gross motor skills. This instability has implications
      for infant screening programs, and supports the premise of serial assessments to
      identify accurately those infants with a motor delay.

PMID- 9783819
TI  - Intrinsic dynamics and mechanosensory modulation of non-nutritive sucking in
      human infants.
AB  - The human infant is endowed with a complex mechanism for the ingestion of
      nutrients that becomes functional in late fetal life. The sucking motor pattern
      is generally accepted to be under the control of pattern generating circuitry
      located in the brainstem reticular formation. Systems under the control of a
      central pattern generator (CPG) may use afferent feedback to allow for changing
      environmental conditions. Although it is clear that afferent pathways serving the
      orofacial region become responsive to mechanical stimulation early in fetal life,
      little is known about the integration of afferent information into the suck CPG.
      The actifier, a device for the mechanical stimulation of intraoral and perioral
      tissues, was designed and used to investigate the response properties of the
      human infant suck CPG to patterned mechanical stimulation. Sinusoid and square
      waveform stimuli elicited responses including modulation of jaw kinematics and
      synchronization [entrainment] of non-nutritive suck motor patterns to the
      mechanical stimulus. These data provide evidence that the suck CPG is responsive
      to mechanical stimulation of perioral and intraoral soft tissues.

PMID- 9783820
TI  - Fluoride profiles of perikymata in enamel surfaces of human premolars.
AB  - Twenty-five premolars (from Nagoya, Japan < 0.1 parts/10(-6)F in drinking water)
      were sampled to determine the fluoride content in imbrication lines of Retzius
      between the grooves and ridges of perikymata on the enamel surface. Eight small
      windows were formed on each surface in groove and ridge regions using an etched
      microsampling technique. By using a regression curve, y = ax(-b), fluoride
      concentrations were compared at depths of 1, 3, 5, 10, 20, 30 and 50 microm in
      the perikymata regions. Fluoride concentrations increased gradually from the age
      of 10 to 12 years on the premolar surfaces, but were significantly higher in 12
      year-olds or older (erupted teeth) than in 10-year-olds or younger (unerupted
      teeth). No obvious difference in fluoride concentrations was found between males
      and females. In the outermost enamel ( < 5 microm depth), fluoride concentrations
      were significantly higher in the grooves than the ridges of the perikymata.
      Comparison of the exponential regression coefficients (-b) of the fluoride
      profiles showed a significant difference between the grooves and ridges. It was
      concluded that fluoride concentrations and profiles were higher in grooves than
      in ridges of perikymata, probably because they are naturally porous and are
      stagnation areas attracting dental plaque.

PMID- 9783821
TI  - Morphological characteristics of primary sensory and post-synaptic sympathetic
      neurones supplying the temporomandibular joint in the cat.
AB  - The cells of origin of peripheral nerves that supply the temporomandibular joint
      were investigated by examining the centripetal transport of wheat germ agglutinin
      horseradish peroxidase (WGA-HRP). Following WGA-HRP injection into the
      temporomandibular joint capsule of the cat, a large number of labelled neurones
      were observed in the trigeminal and superior cervical ganglia ipsilateral to the
      injection site, while no labelled neurones were detected in the cervical dorsal
      root ganglia. Only one labelled neurone was seen in the stellate ganglion.
      Labelled neurones were primarily located in the posterolateral and dorsal regions
      of the trigeminal ganglion, but their distribution in the superior cervical
      ganglion was not localized to specific regions. The labelled neurones in the
      trigeminal ganglion were significantly larger than those in the superior cervical
      ganglion but the sizes of smaller neurones overlapped, suggesting that trigeminal
      ganglion neurones send both myelinated and unmyelinated fibres to the
      temporomandibular joint. The innervation of the temporomandibular joint by
      somatosensory and sympathetic fibres suggests that sympathetic nerves could be
      responsible for allodynia or neuropathic pain caused by temporomandibular
      disorders.

PMID- 9783822
TI  - Involvement of CD14 on human gingival fibroblasts in Porphyromonas gingivalis
      lipopolysaccharide-mediated interleukin-6 secretion.
AB  - The lipopolysaccharides (LPS) of Porphyromonas gingivalis are implicated in the
      initiation and development of periodontal diseases. However, the mechanisms
      underlying P. gingivalis LPS-mediated periodontal destruction are still unknown.
      Here, it was found that P. gingivalis LPS activates human gingival fibroblasts
      (HGF) to release interleukin 6 (IL-6) via CD14. Flow-cytometric analysis showed
      that HGFs bind to fluorescein-isothiocyanate (FITC)-labelled LPS, and express
      CD14 on their surfaces. The binding of FITC LPS was competitively suppressed by
      unlabelled synthetic lipid A as well as by LPS. LPS-induced IL-6 production was
      inhibited by anti-CD14 monoclonal antibody in a dose-dependent manner. The
      binding of FITC LPS to HGF was abrogated by anti-CD14 monoclonal antibody.
      Engagement of LPS initiated the protein tyrosine phosphorylation of several
      intracellular proteins including extracellular signal-regulated kinase (ERK) 1
      and 2, and these events were suppressed by the anti-CD14 monoclonal. These
      results suggest that CD14 is a cell surface binding site for LPS and is involved
      in the LPS-mediated activation of HGF.

PMID- 9783823
TI  - Enzyme activity in parotid and mandibular saliva from red kangaroos, Macropus
      rufus.
AB  - Parotid and mandibular saliva was obtained from red kangaroos by concurrent
      acetylcholine isoprenaline stimulation. Salivary proteins were separated by
      horizontal electrophoresis on either cellulose acetate or starch gels and
      assessed by specific staining techniques for 23 enzymes commonly found in
      mammalian tissues and body fluids. Parotid saliva was positive for acid
      phosphatase, alpha-amylase, carbonic anhydrase, glucose-6-phosphate
      dehydrogenase, sorbitol dehydrogenase and superoxide dismutase activities.
      Mandibular saliva was positive for alcohol dehydrogenase in addition to the above
      six enzymes. The kangaroo salivas lacked activity for alkaline phosphatase, beta
      galactosidase and non-specific esterase which occur in saliva from some mammalian
      species.

PMID- 9783824
TI  - Responses of macrophage-associated antigen-expressing cells in the dental pulp of
      rat molars to experimental tooth replantation.
AB  - Bacterial infection of the dental pulp is a major hindrance to successful pulp
      regeneration after tooth replantation. This study examined how macrophages and
      class II molecule-expressing cells of the pulp respond to tooth replantation, on
      the hypothesis that they contribute to the defence and repair of the traumatized
      pulp. Upper right first molars of 5-week-old male Wistar rats were replanted
      immediately after extraction; contralateral untreated teeth served as controls.
      Pulpal cells expressing macrophage-associated antigens were immunohistochemically
      demonstrated at 0 h (immediately after the replantation) to 84 days
      postoperatively using antirat monoclonal antibodies OX6 (anti-class II
      molecules), ED1 (pan-macrophage antibody, reactive also with dendritic cells) and
      ED2 (anti-resident macrophages). Between 3 and 7 days postoperatively, ED1+ and
      OX6+ cells, but not ED2+ cells, were concentrated in areas of degeneration formed
      in the coronal pulp, and frequently showed a marked accumulation along the pulp
      dentine border of the cuspal area. Confocal laser scanning microscopy revealed
      that some of the OX6+ cells with a dendritic profile extended several cytoplasmic
      processes into the dentinal tubules communicating with the enamel-free area at
      the tip of the cusp. From 14-84 days, approx. two-thirds of specimens exhibited
      pulp-tissue regeneration with increasing formation of reparative dentine.
      Following the formation of sound reparative dentine, cells positive to each
      antibody were distributed more centrally in the pulp than in the controls, and
      thus did not show any accumulation along the pulp-dentine border. However, in the
      other specimens where a bone-like hard tissue had formed in the pulp chamber,
      many ED1+ and OX6+ cells were still concentrated in the remaining pulp tissue and
      showed a marked accumulation along the pulp dentine border. Few ED2+ cells were
      observed in these specimens. These findings suggest that, following tooth
      replantation, exudative macrophages are actively engaged in eliminating dentinal
      tubule-derived infectious stimuli and that class II molecule-expressing cells,
      most probably containing dendritic cells, are positioned strategically at the
      outermost portion of the injured pulp to monitor incoming antigens. The intensity
      of the pulpal defence reaction may be dependent on the status of hard-tissue
      formation, which influences the amount of incoming antigens.

PMID- 9783825
TI  - Oxidative capacity of rat masseter muscle after implantation of thyrotropin
      releasing hormone microspheres in proximity to trigeminal motoneurones.
AB  - Earlier work has shown that two important consequences of implanting thyrotropin
      releasing hormone (TRH) microspheres near motoneurones within the trigeminal
      motor nucleus of actively growing rats are increased muscle mass and a darkening
      of the implant-side masticatory muscles. These phenomena have been associated
      with altered neuromuscular activity patterns and biomechanical forces that
      directly influence craniofacial growth and development. Now, whether the
      implantation of TRH microspheres in proximity to trigeminal motoneurones would
      affect the oxidative capacity of the implant-side masseter muscles was
      investigated. Cytochrome C oxidase (COX) assays were carried out for both implant
      and non-implant-side masseters of TRH (n = 5) and blank microsphere (n = 6)
      Sprague-Dawley rats after stereotactic surgery at 35 days of age. Analyses of
      both groups at 14 days post-implantation revealed that the COX activity levels of
      implant-side masseters in TRH-implanted rats was significantly (P< or =0.05)
      greater than that of non-implant-side masseters; rats implanted with blank
      microsphere exhibited no significant difference between implant- and non-implant
      side masseter COX activity levels. The stated null hypothesis was therefore
      rejected. These data suggest that TRH implants in proximity to trigeminal
      motoneurones effect increased oxidative capacity of the masseter muscle as
      measured by COX activity.

PMID- 9783826
TI  - Interaction of tannin with human salivary proline-rich proteins.
AB  - Tannins are polyphenolic compounds, widely distributed in plant-based foods,
      which have harmful effects on animals including humans. Salivary proline-rich
      proteins (PRPs) may act as a defence against tannins by forming complexes with
      them and thereby preventing their interaction with other biological compounds and
      absorption from the intestinal canal. The aim here was to compare the ability of
      members of the family of human PRPs to form insoluble complexes with tannin and
      to assess the stability of such complexes under conditions similar to those in
      the alimentary tract. Basic PRPs (BPRPs), which have no other known biological
      functions, were very effective in forming insoluble complexes with both condensed
      tannin and tannic acid. Practically no tannin bound to acidic PRPs (APRPs) and
      glycosylated PRPs (GPRPs), suggesting that tannin in the diet would not affect
      their biological activities. There were only small differences in the tannin
      precipitating ability of various BPRPs of different sizes or sequences,
      indicating that, although there is considerable phenotypic variation of PRPs, it
      is not likely to cause marked individual variation in tannin-binding ability.
      Tryptic digestion of an APRP led to a marked increase in tannin binding to the
      resulting proline-rich peptides, supporting observations in other studies that
      there may be an interaction between the proline-poor N-terminal and the proline
      rich C-terminal regions in native APRPs, which inhibits the biological activities
      of the proteins. Deglycosylation of a GPRP also led to a dramatic increase in
      tannin-binding ability, showing that the carbohydrate side-chains prevent binding
      of tannin. Most of the condensed tannin-PRP complexes remained insoluble under
      conditions similar to those in the stomach and small intestine, supporting the
      proposal that PRPs act as a defence against tannin.

PMID- 9783827
TI  - Effects of sodium acetate on rat bone-nodule formation and mineralization in
      vitro.
AB  - Sodium acetate reportedly promotes bone atrophy by inducing resorption and
      inhibiting osteoprogenitor-cell proliferation, but little is known about its
      effects on bone-matrix deposition and mineralization by a population containing
      osteoprogenitor cells. The objective here was to assess the effects of 1-20 mM
      sodium acetate on the proliferation and differentiation of these cells and their
      resultant bone-nodule formation and mineralization in an in vitro assay. Exposure
      to 10 mM sodium acetate had no effect on cellular proliferation but significantly
      increased the production and mineralization of bone nodules (p < 0.01),
      suggesting that it affected osteoprogenitor differentiation and subsequent
      metabolism. However, 10 mM acetate did not increase net bone mass. Dilutions of 1
      5 and 20 mM inhibited cellular proliferation and resultant bone-nodule formation
      and mineralization, significantly reducing the percentage bone area as compared
      to controls (p < 0.001). These data suggest that 1-5 and 20 mM sodium acetate
      significantly inhibit bone deposition, whereas 10 mM has no effects, which could
      contribute to iatrogenic metabolic bone disease in patients receiving either
      renal dialysis or total parenteral nutrition.

PMID- 9783828
TI  - Effects of surfactants on glucosyltransferase production and in vitro sucrose
      dependent colonization by Streptococcus mutans.
AB  - The presence of Tween 80 in media was associated with a significant increase in
      three glucosyltransferases(GTFs)(I, SI and S), especially GTF-I, produced by
      Streptococcus mutans strain PS14, indicating that the surfactant is a major cause
      of the enhanced GTF production observed in cultures in M4 medium. Lecithin and
      Tween 20 also enhanced GTF-I production, while Triton X-100 depressed it. At a
      lot concentration of 0.00125%, Tween 80 enhanced markedly only GTF-I production
      and its effect reached maximum at a concentration of 0.0025%. Water-insoluble
      glucan synthesis and artificial plaque formation (in vitro sucrose-dependent
      colonization) by PS14 were significantly enhanced by the addition of Tween 80 at
      concentrations over 0.00125%. These results suggest that surfactants might vary
      the cariogenic potential of Strep. mutans even at low concentrations.

PMID- 9783829
TI  - Three-dimensional appearance of Langerhans cells in human gingival epithelium as
      revealed by confocal laser scanning microscopy.
AB  - Detailed three-dimensional morphological information of the cell without
      distortion due to thin sectioning can be obtained from thick sections using a
      confocal laser scanning microscope. Here that microscope was used to evaluate
      human gingival Langerhans cells stained with anti-CD1a antibody. Optical
      sectioning and reconstruction by laser scanning microscopy revealed not only
      three-dimensional aspects of Langerhans cells but also spatial information on the
      distribution of their dendritic processes towards the gingival surface. The
      orientated configuration of those processes may reflect the reaction of the
      gingival Langerhans cell to the surrounding moist environment containing
      antigenic stimuli originating in saliva.

PMID- 9783830
TI  - Transforming growth factor-beta superfamily members expressed in rat incisor
      pulp.
AB  - The transforming growth factor (TGF)-beta superfamily comprises more than 35
      structurally related genes that have been implicated in embryonic induction and
      morphogenesis. Different superfamily members may have distinct regulatory roles
      in tooth development and maintenance. Degenerate primer sets derived from the
      highly conserved carboxy terminal region of the TGF-beta superfamily were used
      for reverse transcriptase polymerase with poly(A)+ RNA from the rat incisor pulp
      as a template. TGF-beta superfamily members expressed in the pulp with known
      potential to differentiate into odontoblasts and to form dentine were identified.
      Nucleotide-sequence analysis of the amplified cDNAs identified those encoding
      activin-betaB; bone morphogenic protein (BMP)-2, -4, -7 and -8;
      growth/differentiation factor (GDF)-1, -5 and -6; and glial cell line-derived
      neurotrophic factor. In addition, Northern blot analysis detected TGF-beta1 
      beta2 and -beta3; activin-betaA; BMP-6 and GDF-7 mRNA transcripts in the pulp.
      Coordinated expression of TGF-beta superfamily members in pulp may be critical in
      tooth development and repair.

PMID- 9783831
TI  - AIDS-related malignancies.
AB  - In the US over one million persons are currently infected with the HIV, over half
      a million have had AIDS, and over 300,000 have died from AIDS. Worldwide, it is
      estimated that more than 17 million people are currently infected with HIV, and
      over 1,200,000 cases of AIDS have been reported to the World Health Organization.
      By some estimates, up to 40% of patients with AIDS will ultimately develop some
      form of cancer. Non-Hodgkin's lymphoma, Kaposi's sarcoma and invasive cervical
      cancer have a higher incidence in persons with HIV infection and all three are
      AIDS-defining illnesses. In addition, several reports suggest that a number of
      other malignancies may occur at an increased incidence in persons with HIV
      infection, including squamous-cell carcinoma of the head, neck and anus,
      plasmacytoma, melanoma, small-cell lung cancer, basal-cell cancer, and germ-cell
      tumours. Clinicians should become familiar with HIV-related malignancies as their
      incidence is expected to further increase as more effective therapies for HIV and
      associated opportunistic infections allow patients to live longer in an advanced
      state of immunodeficiency. In the current article, we will review the clinical
      and therapeutic aspects of the most common AIDS-related malignancies including
      non-Hodgkin's and Hodgkin's lymphomas, Kaposi's sarcoma and anogenital epithelial
      neoplasias.

PMID- 9783833
TI  - Sleep-disordered breathing in children.
AB  - The first series of children with obstructive sleep apnoea syndrome was reported
      in 1976. Later it became apparent that children may have breathing disorders
      during sleep without frank apnoea or 'hypopnoeas'. This pattern could be detected
      by measuring the oesophageal pressure. This led to the concept of sleep
      disordered breathing as a spectrum that combines obstructive sleep apnoea
      syndrome and the upper airway resistance syndrome. Studies that do not take into
      account this spectrum may misclassify symptomatic patients as 'primary snorers'.
      The exact prevalence of sleep-disordered breathing in children is unknown but may
      be as high as 11%. There is a familial predisposition to sleep-disordered
      breathing. Nasal obstruction and mouth breathing influence facial growth, which
      may further lead to difficulty in breathing while asleep. Symptoms include an
      increase in total sleep time, nonspecific behavioural difficulties,
      hyperactivity, irritability, bed-wetting and morning headaches. Clinical signs
      include failure to thrive, increased respiratory effort with nasal flaring and
      suprasternal or intercostal retractions. Also, abnormal paradoxical inward motion
      of the chest may occur during sleep. Excessive daytime sleepiness and obesity are
      not always present. Untreated children may develop cardiovascular complications.
      The condition is treatable with continuous or bilevel positive airway pressure,
      and may be cured with surgery.

PMID- 9783832
TI  - Side sleeping position and bed sharing in the sudden infant death syndrome.
AB  - In the last decade there have been major reductions in the sudden infant death
      syndrome (SIDS) rate following prevention programmes in Australasia, Europe and
      North America, mainly due to changing infants from the prone sleeping position
      onto their sides or backs. This report reviews previous SIDS observational
      studies with data on side sleeping position and bed sharing. The relative risk
      for SIDS calculated from previous studies for side vs back sleeping position is
      2.02 (95% CI = 1.68, 2.43). This result suggests that further substantial
      decreases in SIDS could be expected if infants were placed to sleep on their
      backs. With regard to bed sharing, the summary SIDS relative risk is 2.06 (1.70,
      2.50) for infants of smoking mothers and 1.42 (1.12, 1.79) for infants of
      nonsmoking mothers. Public health policy should be directed against bed sharing
      by infants whose mothers smoke as they carry an increased risk of SIDS from bed
      sharing in addition to their already increased risk from maternal smoking. For
      infants of nonsmoking mothers, who have a low absolute risk of SIDS, the 40-50%
      increase in risk needs to be balanced against other perceived benefits from bed
      sharing, such as increased breastfeeding.

PMID- 9783835
TI  - Relationship between contrast sensitivity and metabolic control in diabetics with
      and without retinopathy.
AB  - Contrast sensitivity was studied in diabetic adolescents and young adults with
      and without retinopathy in order to evaluate their central vision, to analyze the
      relationship of metabolic control to the presence and severity of retinopathy,
      and to re-evaluate the response to this test after a significant improvement in
      metabolic control. Twenty adolescent and young adult diabetics without
      retinopathy and 40 diabetics with retinopathy of varying degree were enrolled in
      the study; 20 healthy age and sex-matched subjects served as controls. Contrast
      sensitivity was assessed with a CSV-1000 contrast testing instrument, testing for
      four spatial frequencies, 3, 6, 12 and 18 cycles per degree (cpd). Diabetics with
      no retinopathy showed a weak but significant difference at 18 cpd compared with
      controls (P = 0.04), while diabetics with background retinopathy showed a
      significant reduction of contrast sensitivity at 12 and 18 cpd when compared with
      controls (P < 0.001). In patients with preproliferative/proliferative retinopathy
      a highly significant reduction of contrast sensitivity at all frequencies was
      found compared with controls. Furthermore, these patients had a significantly
      lower mean contrast sensitivity than patients without retinopathy. The patients
      were re-evaluated after a significant amelioration of metabolic control. An
      improvement in contrast sensitivity was found in diabetics without retinopathy
      and with background retinopathy, while there was no change observed in diabetics
      with severe retinopathy. These results show that diabetic adolescents and young
      adults with and without signs of retinopathy observed by fluorescein angiography
      have a reduced contrast sensitivity, which is more severe in patients with
      preproliferative/proliferative retinopathy. A significant amelioration of
      metabolic control is associated with an improvement of contrast sensitivity in
      all patients with the exception of those patients who had signs of
      preproliferative/proliferative retinopathy observed by fluorescein angiography.
      In summary, this longitudinal study provides the first evidence that reduced
      contrast sensitivity is reversible in diabetics with or without background
      retinopathy only.

PMID- 9783834
TI  - Molecular biology of prostate development and prostate cancer.
AB  - The molecular mechanisms that control prostate development have been intensely
      studied in recent years due to the emergence of prostatic cancer as a major
      health concern. Several recent studies have led to the identification of numerous
      genes that are required for prostate organogenesis, many of which also contribute
      to prostate carcinogenesis. These genes fall into several categories, including
      proto-oncogenes, transcription factors, homeobox genes, growth factors and cell
      adhesion molecules. This review focuses on those genes which have been implicated
      in prostate growth and development, and which exhibit deregulated expression in
      prostate cancer.

PMID- 9783836
TI  - Occurrence of HLA-B27 tissue antigen in patients with purulent arthritis caused
      by Staphylococcus aureus or beta-haemolytic streptococci.
AB  - The HLA-B27 tissue antigen is associated with reactive arthritis caused by
      different bacterial infections but its occurrence in purulent arthritis has not
      been studied earlier. We analysed the frequency of HLA-B27 in patients with
      culture proven purulent arthritis caused by Staphylococcus aureus or beta
      haemolytic streptococci. The study included 41 patients treated during the years
      1979-96 (15 female and 26 male) with a mean age of 52 years (range 16-80 years).
      HLA-B27 was found in 24% (9/37) of the tested patients compared with 14% in the
      healthy Finnish population, but the difference was not statistically significant
      (P < 0.50). No statistical difference in disease activity according to febrile
      days or duration of the disease could be found between HLA-B27 positive and
      negative patients. We conclude that HLA-B27 is not a risk factor for purulent
      arthritis, and when present it has no significant modifying effect on the
      clinical picture of purulent arthritis.

PMID- 9783837
TI  - Neural substrates of drug craving and relapse in drug addiction.
AB  - Drug addiction is characterized by motivational disturbances such as compulsive
      drug taking and episodes of intense drug craving. Recent advances using animal
      models of relapse have shown that drug-seeking behaviour can be triggered by drug
      associated cues, by stress and by 'priming' injections of the drugs themselves,
      events also known to trigger drug craving in human drug addicts. Current evidence
      suggests that these stimuli all induce relapse, at least in part, by their common
      ability to activate the mesolimbic dopamine system. Drug-associated cues and
      stress can activate this system via neural circuits from the prefrontal cortex
      and amygdala and through activation of the hypothalamic-pituitary-adrenal axis.
      Our studies suggest that dopamine triggers relapse to drug-seeking behaviour by
      stimulating D2-dopamine receptors which inhibit the cyclic AMP second messenger
      pathway in the neurones of the nucleus accumbens. In contrast, compounds which
      activate D1 receptors prevent relapse to drug-seeking behaviour, possibly through
      satiation of reward pathways. Chronic neuroadaptations in dopamine receptor
      signalling pathways in the nucleus accumbens caused by repeated drug use are
      hypothesized to produce tolerance to the rewarding effects of D1-receptor
      stimulation, leading to increased drug intake during drug self-administration.
      Conversely, these same neuroadaptations are hypothesized to enhance drug craving
      by potentiating D2 receptor-mediated signals during abstinence. These findings
      identify D1 and D2-dopamine receptor mechanisms as potential targets for
      developing anticraving compounds to treat drug addiction.

PMID- 9783838
TI  - Transgenic mice in drug dependence research.
AB  - Transgenic mice with null mutation of specific genes of the central nervous
      system obtained by homologous recombination, called also knock-out mice, have
      been recently used by behavioural neuroscientists to understand better the
      relevance of certain biological mechanisms of drug dependence or addiction. This
      article reviews some of the main contributions to this fastly developing field.
      As addictive drugs exert similar reinforcing effects both in humans and other
      mammals, changes in behavioural performance produced by the motivational effects
      of the addictive drugs in knock-out mice can give important information about the
      relevance of that particular gene product (eg a neurotransmitter receptor) for
      the pathogenicity of substance abuse disorders. In same cases the deletion of a
      given gene for a neurotransmitter receptor involved in the action of addictive
      drugs is associated with a phenotype that reproduces the effects obtained by the
      pharmacological administration of an antagonist for the same receptor. In other
      instances, surprising results are obtained, the most striking being the evidence
      that mice lacking the dopamine transporter gene, the most important binding site
      of cocaine, retain the capability to self-administer cocaine intravenously.
      Because the gene deletion is operative during embryogenesis, some adaptive
      compensatory mechanisms may produce unexpected results, suggesting caution in the
      interpretation of these results. The advent of tissue-specific inducible knock
      out mice will soon produce a second revolution in the field of substance abuse
      research.

PMID- 9783839
TI  - Role of the limbic system in dependence on drugs.
AB  - The limbic system is a group of structurally and functionally related areas of
      the brain that provides the anatomical substrate for emotions and motivated
      behaviour, including the circuitry for the stress response and reward-related
      events. This system is strongly implicated in drug abuse from the pleasure and/or
      positive side associated with acute exposure to the dysphoria and craving
      associated with withdrawal. The contribution of the main cortical and subcortical
      elements of the limbic system to drug dependence is briefly reviewed in the
      present work with a focus on the role of the extended amygdala and its
      connections as well as on the peripheral feedback signals mediated by adrenal
      glucocorticoids. The elucidation of the neuroadaptive responses of the limbic
      system to chronic drug exposure will undoubtedly help to design rational
      strategies for the treatment of addiction.

PMID- 9783840
TI  - New treatment options for substance abuse from a public health viewpoint.
AB  - Naltrexone is the first safe and effective pharmaceutical adjunct for use in the
      treatment of alcohol abuse. Theoretically it could be effective also as a means
      for terminating methadone maintenance and in the treatment of other forms of
      substance abuse. Two general types of protocols have been used with naltrexone.
      One protocol is similar to the protocol appropriate for use with disulfiram; it
      is designed to preclude use of the substance while on naltrexone. The other
      protocol is based on preclinical research showing that opioid antagonists can
      cause extinction of alcohol drinking; it is designed to maximize the effects from
      extinction. The results from the clinical trials are consistent with the
      conclusion that the major benefits from naltrexone treatment, regardless of
      protocol, are being caused by extinction. The extinction protocol is better from
      the position of public health, increasing the range of patients who can be
      treated, reducing the total cost and allowing patients to be treated with
      dignity. Pharmacological extinction is a new form of medicine, shown to be highly
      accessible and effective in treating excessive drinking and providing interesting
      possibilities for the treatment of other learned behavioural disorders.

PMID- 9783842
TI  - Studies on the origin of redox enzymes in seminal plasma and their relationship
      with results of in-vitro fertilization.
AB  - Glutathione (GSH), GSH peroxidase (GPX), GSH reductase (GRD), superoxide
      dismutase (SOD) and catalase-like enzyme activity were quantified in seminal
      plasma from normozoospermic patients, men with known distal ductal occlusion,
      proven fathers and male partners of couples receiving in-vitro fertilization
      (IVF) treatment for both male and female causes. Glutathione was non-detectable
      (< 2.5 microM) in seminal plasma. None of the enzyme activities per unit volume
      were lower in semen from vasectomized men, suggesting that they did not originate
      substantially from the testis or epididymis. The strongest relationships between
      enzyme activities and accessory gland markers were between zinc and GRD (r =
      0.678), SOD (r = 0.602) and GPX (r = 0.548), suggesting a largely prostatic
      origin of these enzymes. Only weak relationships between accessory gland markers
      and catalase-like activity suggested a multi-glandular source of this enzyme.
      There was no relationship between the activity of any of the enzymes in the IVF
      patients with their fertilization rates in vitro or the establishment of
      pregnancy after IVF. Nor was there any correlation of enzyme activity with the
      morphology and percentage of motile spermatozoa in semen or with the percentage
      motility of spermatozoa immediately after swim-up or after overnight incubation.
      These findings suggest that the protective enzymes in the seminal plasma are
      contributed largely by the prostate and little by the epididymis, and that in
      most cases of IVF, they have no major influence on the outcome.

PMID- 9783841
TI  - Expression of DAZ (deleted in azoospermia), DAZL1 (DAZ-like) and protamine-2 in
      testis and its application for diagnosis of spermatogenesis in non-obstructive
      azoospermia.
AB  - Spermatogenesis is regulated by hormones, local regulatory factors in the testes
      and specific gene expression of spermatogenic cells in humans. In this study, we
      have detected the expression of the deleted in azoospermia (DAZ), the DAZ-like
      autosome (DAZL1), and the protamine-2 genes in spermatogenic cells.
      Spermatogenesis in 38 male infertility patients was evaluated by the semen
      analysis and histological examination. Patients were diagnosed as Sertoli cell
      only syndrome (n = 20), maturation arrest (n = 6), hypospermatogenesis (n = 6),
      and obstructive azoospermic patients with normal spermatogenesis (n = 6). After
      microscopic observation of the wet preparation of the testis tissues,
      seminiferous tubule contents were used for reverse transcription-polymerase chain
      reaction (RT-PCR) analysis of DAZ, DAZL1 and protamine-2. In cases with Sertoli
      cell only syndrome, we found spermatogenic cells in 30% of patients (6/20) by the
      wet preparation method. There was no difference between the histology and the wet
      preparation results in maturation arrest and obstructive azoospermia; however, in
      one case of hypospermatogenesis, spermatozoa were not detectable by the wet
      preparation method. Using in-situ hybridization with DAZ and protamine-2
      ribonuclear probes, we confirmed spermatogenic cell-specific expression of DAZ
      (spermatogonia/early spermatocyte) and protamine-2 (spermatid/spermatozoon). DAZ
      and protamine-2 expression can therefore be considered spermatogenic cell markers
      and could be useful in molecular diagnosis of spermatogenesis. In 13 patients
      with spermatozoa under the wet preparation, the expression of DAZ, DAZL1 and
      protamine-2 was detected in all the preparations. In one wet preparation showing
      only spermatogonia/spermatocyte, only DAZ and DAZL1 RNA were detected. In 14 wet
      preparations showing no spermatogenic cells, DAZ, DAZL1 and protamine-2 were not
      detected except in one preparation where DAZL1 expression was detected. In 10 wet
      preparations representing spermatogonia/spermatocyte to spermatids, but showing
      no spermaozoa, DAZ and DAZL1 were detected in eight and nine preparations
      respectively, and protamine-2 was detected in six preparations. These results of
      gene expression were similar to the wet preparation results. RT-PCR for DAZ,
      DAZL1 and protamine-2 was informative for the existence of germ cells, germ cell
      physiology and differentiation. From these results, we suggest that the analysis
      of DAZ, DAZL1 and protamine-2 expression by RT-PCR and wet preparation might
      offer a better method for finding the spermatogenic cells compared to the
      histological method.

PMID- 9783843
TI  - Expression of extracellular glutathione peroxidase type 5 (GPX5) in the rat male
      reproductive tract.
AB  - The mammalian epididymis is the site of expression and secretion of an abundant,
      tissue-specific, androgen-regulated, selenium-independent, glutathione peroxidase
      isoenzyme (GPX5), which has been proposed to play a role in protecting the
      membranes of spermatozoa from the damaging effects of lipid peroxidation and/or
      preventing premature acrosome reaction. Using a combination of reverse
      transcription-polymerase chain reaction, Northern blot analysis and Western
      blotting, we now describe in detail the developmental expression of GPX5
      transcripts and protein in the rat epididymis and characterize the association of
      rat GPX5 with the sperm plasma membrane.

PMID- 9783844
TI  - Phosphoinositide 3-kinase is involved in the induction of the human sperm
      acrosome reaction downstream of tyrosine phosphorylation.
AB  - In somatic cells phosphoinositide 3-kinase (PI 3-kinase) is activated upon
      interaction with both receptor tyrosine kinases (RTK) and G-proteins resulting in
      the production of moieties involved in the inositol phospholipid signalling
      pathway. As G proteins, RTK and the inositol phospholipids have all been
      implicated in the human sperm acrosome reaction, experiments were carried out to
      determine whether PI 3-kinase was also involved in this phenomenon. Wortmannin is
      a selective inhibitor of PI 3-kinase and was shown to significantly inhibit the
      acrosome reaction induced by both mannose-bovine serum albumin (mannose-BSA) (10,
      50 and 100 nM) and a polyclonal antibody raised against an extracellular region
      of the sperm zona receptor kinase (ZRK, at 100 nM only). Wortmannin did not
      inhibit the A23187- or progesterone-induced acrosome reaction. These results
      suggest that PI 3-kinase is involved in the human sperm acrosome reaction. The
      levels of tyrosine phosphorylation of sperm proteins as detected by Western
      blotting using antiphosphotyrosine antibodies was not affected by wortmannin in
      agonist (A23187 and mannose-BSA)-stimulated spermatozoa. This indicated that PI 3
      kinase operates downstream of tyrosine phosphorylation in the signal transduction
      cascade which leads to the human sperm acrosome reaction.

PMID- 9783845
TI  - Protein and enzyme patterns in the fluid cavities of the first trimester
      gestational sac: relevance to the absorptive role of secondary yolk sac.
AB  - The potential absorptive role of the yolk sac membrane was evaluated by examining
      protein and enzyme patterns in embryonic fluids and by comparing the synthetic
      capacity of the secondary yolk sac, fetal liver and placenta for human chorionic
      gonadotrophin (HCG) and alpha-fetoprotein (alphaFP). In yolk sac fluid samples,
      protein electrophoresis showed two main electrophoretic bands with mobilities
      comparable to those of albumin and interalbumin-alpha1-globulin, and
      immunoblotting revealed the presence of albumin, alphaFP, alpha1-antitrypsin,
      alpha2-macroglobulin, transferrin, complement factors 3 and 4 and immunoglobulin
      G. In coelomic fluid, similar results were obtained, except for the absence of
      alpha2-macroglobulin and the presence of ceruloplasmin and IgA. After
      electrophoresis and immunoblotting with specific antibodies, beta-HCG was
      detected in all placental homogenates and culture media but was not revealed in
      any of the corresponding yolk sac tissue samples. Reverse transcription
      polymerase chain reaction (RT-PCR) showed that all placental samples express beta
      HCG mRNA whereas all yolk sac and liver samples express alphaFP mRNA. These
      findings suggest that the yolk sac membrane is an important zone of transfer
      between the extra-embryonic and embryonic compartments and may also help to
      further develop therapeutic protocols making use of fetal somatic gene therapy by
      injecting transduced cells into the exocoelomic cavity.

PMID- 9783846
TI  - Scoring criteria for preimplantation genetic diagnosis of numerical abnormalities
      for chromosomes X, Y, 13, 16, 18 and 21.
AB  - Fluorescence in-situ hybridization (FISH) for application in preimplantation
      genetic diagnosis (PGD) of aneuploidy has been used successfully, but stringent
      scoring criteria to score FISH signals have not been developed. In the present
      study a FISH protocol to simultaneously enumerate chromosomes X, Y, 13, 16, 18,
      and 21 was used to evaluate two different scoring criteria. The criteria consider
      hybridization signal size, shape, and vicinity to other signals and nuclear
      diameter. For this purpose, 74 embryos (412 blastomeres) donated for research had
      most or all of their cells analysed. The least error-prone criterion (9%) was
      selected for use in PGD cases. Some probes produced more errors than others, and
      these criteria may provide clues to improve these probes. The same probe solution
      was applied to 55 PGD cases and a total of 307 embryos. Of the non-transferred
      embryos, 67 were fully reanalysed and 1.5% (1/67) of them were falsely diagnosed
      as normal, while 19% (13/67) were falsely diagnosed as abnormal. Twelve of the
      patients became pregnant after PGD.

PMID- 9783847
TI  - Preimplantation genetic diagnosis of DiGeorge syndrome.
AB  - We report the first case of preimplantation genetic diagnosis used in order to
      avoid chromosomal imbalance in the progeny of a woman mildly affected by DiGeorge
      syndrome and carrier of a microdeletion of chromosome 22q11.2. In total, seven
      embryos were biopsied in three separate treatments and analysed by fluorescent in
      situ hybridization (FISH). Of these, four were carrying the deletion, two were
      normal and in one the analysis was inconclusive. The diagnostic procedure was
      performed within 5 h. This allowed the biopsied embryos to be transferred the
      same day as the biopsy was taken (day 3). Two embryos were transferred in the
      third treatment, but no pregnancy was established. Patients with a 22q11
      microdeletion, who have a 50% risk of transmitting the deletion to their
      offspring, can now be offered preimplantation genetic diagnosis using FISH for
      the detection of a 22q11 deletion.

PMID- 9783848
TI  - Hydatidiform moles associated with multiple gestations after assisted
      reproduction: diagnosis by analysis of DNA fingerprint.
AB  - In spite of the widespread use of assisted reproductive technology, there have
      been, to our knowledge, only two reported cases of molar pregnancies after gamete
      intra-Fallopian transfer and five reported cases after in-vitro fertilization and
      embryo transfer. We report here a case of a complete hydatidiform mole in a twin
      pregnancy after gamete intra-Fallopian transfer, as well as a case of a complete
      hydatidiform mole in a triplet pregnancy after in-vitro fertilization and embryo
      transfer. The genetic constitution of each conceptus was determined by
      examination of the restriction fragment length polymorphism of the DNA with four
      different single-locus probes. This analysis revealed that both hydatidiform
      moles were of androgenetic origin and probably of monospermic origin. Moreover,
      the analysis confirmed that the pregnancies were dizygotic and trizygotic
      pregnancies respectively. The diagnostic utility of the analysis of DNA
      polymorphism is discussed in cases of a molar pregnancy with coexisting fetuses.

PMID- 9783849
TI  - Preimplantation genetic diagnosis of spinal muscular atrophy.
AB  - After Duchenne muscular dystrophy, spinal muscular atrophy (SMA) is the most
      common severe neuromuscular disease in childhood. Since 1995, homozygous
      deletions in exon 7 of the survival motor neuron (SMN) gene have been described
      in >90-95% of SMA patients. However, the presence of a highly homologous SMN copy
      gene complicates the detection of exon 7 deletions. This paper describes the
      adjustment and evaluation of an established SMN exon 7 polymerase chain reaction
      (PCR) protocol at the single cell level, and the first preimplantation genetic
      diagnosis (PGD) of SMA with this PCR protocol. To determine PCR efficiency and
      allelic loss, 200 leukocytes of normal individuals, SMA carriers and patients,
      and 25 blastomeres were tested. The PCR efficiency of the SMN exon 7 and the
      adjacent copy gene sequence, tested in the leukocytes, were 90% and 91%
      respectively. No allelic loss was detected. One out of 25 blastomeres tested
      revealed a negative PCR signal for the SMN exon 7 sequence. All 25 showed the
      copy gene sequence. PGD of SMA was offered to a couple with an affected child
      homozygous for the SMN exon 7 deletion. After intracytoplasmic sperm injection,
      four and five embryos could be genotyped for the SMN exon 7 in two cycles
      respectively. After embryo transfer in the second PGD cycle an ongoing gemelli
      pregnancy was achieved. This study demonstrates that PGD for SMA is feasible when
      a previous child is homozygous for the SMN exon 7 deletion.

PMID- 9783850
TI  - Mitochondrial DNA deletion in human oocytes and embryos.
AB  - Mitochondrial DNA (mtDNA) deletions are present in both human oocytes and
      embryos. It has been found that these tissues contain a mtDNA mutation which is
      present in high amounts in patients with Kearns-Sayre syndrome (KSS) and
      progressive external ophthalmoplegia. In the present study, the frequency of this
      KSS deletion was investigated in human oocytes and embryos. Using a nested primer
      polymerase chain chian reaction (PCR) strategy, the frequency of the KSS deletion
      in 74 human oocytes and 137 embryos was found to be 32.8 and 8.0% respectively.
      Using a 'long PCR-short PCR' nested primer strategy, the frequency of the KSS
      deletion in 181 human oocytes and 104 embryos was found to be 47.0 and 20.2%
      respectively. There was no statistical correlation between the age of the
      patients at the time of oocyte retrieval and the presence of the deleted
      molecules. There was a statistical difference between the presence of the deleted
      molecules in oocytes versus embryos using either technique (P < 0.0001). The
      relevance of these findings to the accumulation of low levels of deleted mtDNA in
      both oocytes and embryos is discussed in this study.

PMID- 9783851
TI  - Expression of gonadotropin-releasing hormone (GnRH) gene in human uterine
      endometrial tissue.
AB  - Many peripheral reproductive tissues have been found to contain gonadotrophin
      releasing hormone (GnRH) and express the GnRH gene at low levels, presumably
      because the hormone functions in a paracrine/autocrine fashion. This study was
      designed to investigate and characterize GnRH gene expression in human
      endometrial tissue at different stages of the endometrial cycle. Reverse
      transcriptase-polymerase chain reaction (RT-PCR) analysis together with Southern
      blot assay demonstrated that human endometrial tissue expresses the proGnRH gene.
      RNA samples from endometrial tissue were analysed with two pairs of
      oligonucleotide primers. Both gave a doublet 870 bases apart at the expected
      sizes, indicating that both the upstream and downstream transcriptional start
      sites of the GnRH gene are used in endometrial tissue and that transcripts with
      and without intron 1 were produced. Our data also demonstrated that utilization
      of the two promoters varies with the stage of the endometrial cycle. The largest
      difference came from the mRNA transcribed from the downstream promoter and
      without intron 1. This mRNA was expressed at a very low level during the
      proliferative phase and dramatically increased almost 10-fold (P < 0.01) during
      the early secretory phase, and subsequently decreased 5-fold during the late
      secretory stage. The presence of GnRH mRNA in the endometrium, as well as the
      differential expression of the GnRH gene during the early secretory phase
      provides physiological evidence that human GnRH may play a paracrine/autocrine
      function in the human uterus.

PMID- 9783852
TI  - Involvement of cyclin-dependent kinase inhibitor p27Kip1 in growth inhibition of
      endometrium in the secretory phase and of hyperplastic endometrium treated with
      progesterone.
AB  - A cyclin-dependent kinase (cdk) inhibitor, p27Kip1 (p27), binds to the cyclin E
      cdk2 complex and functions as a suppressor of cell cycle promotion. Here, the
      involvement of p27 in the growth of normal human endometrium was
      immunohistochemically studied, and the findings were compared with those of Ki
      67, cyclin E and cdk2. In addition, to elucidate the effect of progesterone on
      the expression of p27, tissues from patients with endometrial hyperplasia were
      examined before and after the administration of medroxyprogesterone acetate (MPA)
      for the treatment of this disease. In the glandular cells of the normal
      endometrium, p27 was negligible during the proliferative phase, whereas it was
      markedly increased in the secretory phase. The staining pattern of Ki-67 was the
      reverse. Cyclin E/cdk2-positive cells were observed throughout the menstrual
      cycle. In the secretory phase, the cyclin E/cdk2-positive cells were also
      positive for p27, suggesting an interaction between these molecules. Stromal
      cells, especially in the basalis, showed a consistent expression of p27
      throughout the menstrual cycle. The expression of p27 in hyperplastic epithelia
      before the MPA treatment was negligible, whereas it was greatly increased after
      the treatment. The Ki-67 positivity decreased after the treatment. These findings
      suggest that p27 is involved in the progesterone-induced growth suppression of
      normal and hyperplastic endometria.

PMID- 9783853
TI  - Functional role of focal adhesion kinase in the process of implantation.
AB  - The expression and function of focal adhesion kinase (FAK) in human decidual
      cells were investigated. This kinase is localized to focal adhesions in
      fibroblasts, and is phosphorylated on tyrosine in normal and src-transformed
      fibroblasts. Immunofluorescent staining revealed that the cultured decidual cells
      expressed high levels of FAK at the cell periphery. Double stainings for FAK and
      phosphotyrosine, FAK and talin, and FAK and beta1 integrin demonstrated that FAK
      co-localized with integrins in cellular focal adhesions. Mouse blastocysts became
      attached to cultured decidual cells after embryos hatched from the zona
      pellucida. The majority of hatched blastocysts attached to human decidual cells
      within 24 h of culture. Blastocysts attached to decidual cells exhibited
      extensive outgrowth after 48 h. Treatment of decidual cells with herbimycin A, a
      tyrosine kinase inhibitor, did not affect the rate of hatching or attachment of
      blastocysts. However, the outgrowth of embryos on the decidual cells was
      inhibited by the addition of herbimycin A in a dose-dependent manner, implying
      that blastocyst attachment and outgrowth are mediated by different mechanisms.
      This study suggests that tyrosine phosphorylation of FAK on decidual cells may be
      important in development and differentiation following attachment.

PMID- 9783854
TI  - Nitric oxide mediated inhibition of contractile activity in the human uterine
      cervix.
AB  - Nitric oxide (NO) is an important modulator of contractile activity in various
      tissues. The aim of the present study was to investigate the possible existence
      of an NO system within the human uterine cervix and to study the effects of NO on
      the cervix in early pregnancy. Cervical tissue specimens were obtained from 24
      women in connection with first trimester legal abortion. NADPH diaphorase
      staining was used to identify nitric oxide synthase activity within the cervical
      tissue. Cylindrical tissue specimens were mounted in organ bath chambers for
      isometric registration of contractile activity. The presence of a functional NO
      system in the cervix was investigated by adding either sodium nitroprusside or
      spermine NONOate, two different NO donors, or 8-bromo cGMP, an analogue of the
      second messenger cyclic guanosine monophosphate (cGMP), to the organ baths.
      Positive NADPH diaphorase staining was clearly observed in the walls of blood
      vessels, in cervical smooth muscle cells, and cells scattered in the connective
      tissue. The NO donating drugs sodium nitroprusside and spermine NONOate both
      caused a dose-dependent inhibition of spontaneous contractile activity with
      significant inhibition at concentrations of 10(-5) and 10(-7) M respectively.
      Furthermore, the participation of NO in the regulation of cervical contractility
      was indicated by a significant concentration-dependent inhibition of spontaneous
      contractions when 8-bromo cGMP (10(-5)-10(-3) M) was added to the organ baths.
      The study indicates the existence of an NO system within the human uterine cervix
      and a role of NO in control of cervical function.

PMID- 9783856
TI  - Assignments of meaning in epidemiology.
AB  - Epidemiology works in a public domain, gathering the results of surveys and
      trials into forms of knowledge which are made available to many stakeholders.
      Health policy makers, lawyers, the media, medical technology companies, and those
      who use and deliver health services all have legitimate interests in
      epidemiology. There is unfortunately no common language in which each of these
      stakeholders can express their interest in the outcomes of epidemiological
      studies. The largest and most important gap exists between those who use
      computational data and those who use cultural and linguistic models to generate
      their explanations. Methods have been described, however, which allow the
      identification of all legitimate stakeholders before epidemiological studies are
      undertaken. Identifying the stakeholders, however, will serve no purpose unless
      there is a prior commitment by epidemiologists to respect both reductionist and
      narrative accounts of truth.

PMID- 9783855
TI  - Correlation between alpha1/beta-adrenoceptor ratio and spontaneous uterine motor
      activity in the post-partum rat.
AB  - The spontaneous uterine motor activity of the post-partum rat was investigated in
      parallel with the in-vitro determination of the density of the alpha1 and beta
      adrenergic receptors of the myometrium. The in-vivo experiments were performed by
      an improved method, using a Millar catheter fitted with a latex microballoon. The
      spontaneous contractility of the post-partum rat uterus was found to be highest
      24 h after delivery, indicating that this time is the most suitable for
      pharmacological examinations of tocolytic agents. A very close correlation was
      found between the results of the in-vivo experiments and the alpha1/beta
      adrenergic receptor ratio assessed by an in-vitro receptor assay, thus indicating
      that the state of the adrenergic receptor system fundamentally determines the
      contractility of the uterus. This conclusion is supported by the fact that the
      pharmacological sensitivity of the rat uterus to prazosin and fenoterol changed
      as a function of the post-partum time in accordance with the alpha1/beta
      adrenoceptor ratio. These results and the relevant data available reveal a
      crucially important role of an alpha1-adrenoceptor-mediated process, implicating
      alpha1-blockers as theoretically potent agents for inhibition of premature
      uterine contractions.

PMID- 9783857
TI  - "Death by proxy": ethics and classification in epidemiology.
AB  - Epidemiology is reductionist in that it usually relies on creating categories of
      people or risk factors. Classification must be undertaken as part of any study,
      however by the act of choosing groups, individuals are (potentially) consigned to
      either a higher or lower risk group. We discuss this from an ethical perspective
      and consider: (a) whether the groupings commonly chosen genuinely represent the
      risk factor of interest, (b) the implications for individuals when consigned to
      groups and (c) the implications for epidemiology.

PMID- 9783859
TI  - The ethics of attribution: the case of health care outcome indicators.
AB  - The ethical basis of clinical outcomes measurement is a desire to improve care in
      a way which will increase both clinical effectiveness and value for money
      beneficence as well as competence. To date in the U.K., any debate about
      producing comparative indicators of clinical outcomes has been concerned mainly
      with the unfairness to individual doctors or clinical teams of judging their
      performance on this basis. There has been less interest in the prime purpose of
      such production, which is to increase the accountability and effectiveness of the
      NHS as a publicly funded service. Rather than working to improve clinical
      effectiveness and outcomes within clinical services, health authorities which
      wish to improve outcomes for their populations have been encouraged simply to
      shift the contract to another provider of care. The key issue on which the ethics
      of either action rests is the extent to which the attribution of outcome to
      intervention is valid and reliable and, therefore, that judgements about
      performance are just and thus ethical. The consequence of unjust judgements may
      be to increase the inequalities that medical care resource allocation should
      attempt to reduce.

PMID- 9783858
TI  - Is imposing risk awareness cultural imperialism?
AB  - Epidemiology is the main supplier of "bases of action" for preventive medicine
      and health promotion. Epidemiology and epidemiologists therefore have a
      responsibility not only for the quality and soundness of the risk estimates they
      deliver and for the way they are interpreted and used, but also for their
      consequences. In the industrialised world, the value of, and fascination with
      health is greater than ever, and the revelation from epidemiological research of
      new hazards and risks, conveyed to the public by the media, has become almost an
      every-day phenomenon. This "risk epidemic" in the modern media is paralleled in
      professional medical journals. It is in general endorsed by health promoters as a
      necessary foundation for increased health awareness and a desirable impetus for
      people to take responsibility for their own health through behavioural changes.
      Epidemiologists and health promoters, however, have in general not taken the
      possible side effects of increased risk awareness seriously enough. By increasing
      anxiety regarding disease, accidents and other adverse events, the risk epidemic
      enhances both health care dependence and health care consumption. More
      profoundly, and perhaps even more seriously, it changes the way people think
      about health, disease and death--and ultimately and at least potentially, their
      perspective on life more generally. The message from the odds ratios from
      epidemiological research advocates a rationalistic, individualistic, prospective
      life perspective where maximising control and minimising uncertainty is seen as a
      superior goal. The inconsistency between applying an expanded health concept,
      comprising elements of coping, self-realisation and psycho-physical functioning,
      and imposing intolerance to risk and uncertainty, is regularly overlooked.
      Acceptance and tolerance of risk and uncertainty, which are inherent elements of
      human life, is a prerequisite for coping and self-realisation. A further shift
      away from traditional working-class values like sociability, sharing,
      conviviality and tolerance can not be imposed without unwanted side effects on
      culture and human interaction. The moral and coercive crusade for increased risk
      awareness and purity in life style can too readily take on the form of cultural
      imperialism towards conformity. Epidemiologists and the health care movement in
      general have a mandate to fight disease and premature death; they have no
      explicit mandate to change culture.

PMID- 9783860
TI  - "Communitarian claims" as an ethical basis for allocating health care resources.
AB  - This paper presents the case for re-examining the most commonly adopted basis of
      resource allocation in health care, i.e. need. The key problems identified with
      most needs approaches are (a) defining its precise meaning, (b) that the
      community is seldom consulted as to first what constitute needs for health care
      or second what relative weights are to be attached to health gains aimed at
      addressing different needs and (c) more generally, proceeding without knowing
      what the community wants the objectives of health care to be. It is suggested
      that John Broome's notion of "claims", especially what this paper calls
      "communitarian claims", may be helpful in providing a better basis for allocating
      health care resources. Such "communitarian claims" allow inter alia for the
      community to be involved in setting the social choice rules with respect to the
      governance of health care and for determining what it is that it (the community)
      wants from its health service. The links to rights are also identified and the
      advantages of communitarian claims over both a simple concept of need and rights
      are set out, without arguing that either needs (or rights) ought necessarily to
      be abandoned as bases for resource allocation in health care.

PMID- 9783861
TI  - Social capital and health: implications for public health and epidemiology.
AB  - Public health and its "basic science", epidemiology, have become colonised by the
      individualistic ethic of medicine and economics. Despite a history in public
      health dating back to John Snow that underlined the importance of social systems
      for health, an imbalance has developed in the attention given to generating
      "social capital" compared to such things as modification of individual's risk
      factors. In an illustrative analysis comparing the potential of six progressively
      less individualised and more community-focused interventions to prevent deaths
      from heart disease, social support and measures to increase social cohesion
      faired well against more individual medical care approaches. In the face of such
      evidence public health professionals and epidemiologists have an ethical and
      strategic decision concerning the relative effort they give to increasing social
      cohesion in communities vs expanding access for individuals to traditional public
      health programs. Practitioners' relative efforts will be influenced by the kind
      of research that is being produced by epidemiologists and by the political
      climate of acceptability for voluntary individual "treatment" approaches vs
      universal policies to build "social capital". For epidemiologists to further our
      emerging understanding of the link between social capital and health they must
      confront issues in measurement, study design and analysis. For public health
      advocates to sensitise the political environment to the potential dividend from
      building social capital, they must confront the values that focus on individual
      level causal models rather than models of social structure (dis)integration. The
      evolution of explanations for inequalities in health is used to illustrate the
      nature of the change in values.

PMID- 9783862
TI  - Ethics, epidemiology and the thrifty gene: biological determinism as a health
      hazard.
AB  - This paper briefly describes the rise of the thrifty genotype hypothesis as an
      explanation for the late twentieth century epidemic of diabetes, particularly in
      post-colonial indigenous societies. It looks at some of the ethical consequences
      of the biological deterministic paradigm, particularly the popular confusion of
      "genes" with "race" and how this paradigm served to exclude consideration of
      social determinants of disease in epidemiological thinking. Some alternative
      hypotheses to the thrifty gene theory are explored, together with the
      consequences of acceptance of these other theories in terms of public health
      action. Finally, there is a need for epidemiology to be continually conscious,
      critical and transparent with respect to the general disease (and wellness)
      theory under which it operates if it is to be truly a science rather than a
      collection of methodologies.

PMID- 9783864
TI  - Inequalities in the transition of ischaemic heart disease mortality in New South
      Wales, Australia, 1969-1994.
AB  - This paper examines changes in ischaemic heart disease mortality in New South
      Wales between 1969 and 1994, with particular reference to the 1969-1973, 1979
      1983, 1985-1989 and 1990-1994 periods. Using death certificate data and unit list
      mortality files, and considering occupational differentials among males, and
      marital status and regional and intra-metropolitan variations among males and
      females, the question whether changes in differentials in mortality from heart
      disease occurred during this mortality transition is asked. Mortality from
      ischaemic heart disease declined in all marital status and occupational status
      groups, and in all geographical areas, but it declined more slowly among never
      married and divorced males, among manual workers, and in lower income areas.
      Whereas ischaemic heart disease mortality was lower in most rural areas than in
      metropolitan Sydney at the beginning of the period, in the 1990s it was
      significantly more elevated in inland small towns and rural areas than in the
      metropolis. Differentials increased over time, more especially with males.

PMID- 9783863
TI  - A tale of two (low prevalence) cities: social movement organisations and the
      local policy response to HIV/AIDS.
AB  - In the field of HIV/AIDS, social movement organisations (SMOs) have been
      identified as powerful potential catalysts for change through their impact on
      formal organisational structures and the policy process. In addition, they have
      the capacity to be important providers of services in their own right, through
      the community resources they are capable of mobilising. In the United Kingdom,
      however, their role in policy formation is disputed. Previous studies have
      concluded that they have been most influential at national policy and ward level.
      At the level of local policy making, their influence has been found to be patchy
      and confined largely to securing recognition of HIV as an issue. Most previous
      research has, however, been conducted in high prevalence, metropolitan settings
      with functional SMOs. This paper presents the results of a comparative case study
      of two neighbouring provincial low prevalence district health authorities (HAs)
      in England. We describe the changing national policy context from 1986 to 1995
      and use a strategic change model to analyse the local development of care and
      treatment services for people with HIV/AIDS, in particular the relationship
      between SMOs and HAs. Despite being demographically, socioeconomically and
      epidemiologically similar, and sharing an identical national policy framework,
      the two districts demonstrate completely divergent organisational responses to
      the HIV/AIDS epidemic. We conclude that the level of prior social movement
      mobilisation and the degree of receptivity for change within the HA are the key
      variables for explaining variations in the scale of strategic change observed in
      the two districts.

PMID- 9783865
TI  - Towards quality of care in child health programmes: a challenge for the
      partnership in health and social sciences.
AB  - Several child health care programmes, though often well conceived, are poorly
      implemented at field level and focus primarily on quantitative achievements to
      the neglect of quality of care. This paper presents a quality of care (QOC)
      framework for child health programmes from the perspectives of the management
      system of an organization and the provider-client interface at point of service
      delivery. The paper subsequently describes the application of qualitative and
      quantitative research tools drawn from the social sciences and health sciences
      for planning and evaluating quality of care. An integrated and complementary use
      of these tools is recommended. It is suggested that minimum standards, which are
      region specific, be articulated for quality maintenance in child health
      programmes. These standards may be upgraded as quality improves. Finally, the
      challenges which a partnership of the health and social sciences may have to take
      up are discussed. These include advocacy for prioritization of QOC in child
      health programmes, facilitating an environment which supports quality of care,
      promoting inter-disciplinary action research, training students in social science
      research in universities and research organizations, documenting success stories.

PMID- 9783866
TI  - Childhood conditions that predict survival to advanced ages among African
      Americans.
AB  - This paper investigates the social and economic circumstances of childhood that
      predict the probability of survival to age 85 among African-Americans. It uses a
      unique study design in which survivors are linked to their records in U.S.
      Censuses of 1900 and 1910. A control group of age and race-matched children is
      drawn from Public Use Samples for these censuses. It concludes that the factors
      most predictive of survival are farm background, having literate parents, and
      living in a two-parent household. Results support the interpretation that death
      risks are positively correlated over the life cycle.

PMID- 9783867
TI  - Higher earnings, bursting trains and exhausted bodies: the creation of travelling
      psychosis in post-reform China.
AB  - This paper examines the biomedical construction of "travelling psychosis" (TP), a
      contested psychiatric diagnosis pertaining to a severe mental disturbance that
      occurs among migrant workers who travel long distance in China's overcrowded
      trains. Although TP can produce substantial psychiatric morbidity, it is also a
      socially constructed entity that serves social uses. By subscribing to a
      ritualistic model of validation and by invoking the rhetoric of scientific
      authority, Chinese psychiatrists who created TP have been able to accomplish such
      goals as legitimating its forensic function, securing research funds, enhancing
      their academic status and raising railway authorities' consciousness about
      passengers' safety issues. But the "biopsychosocial" paradigm they espouse
      supplies only a parochial form of social analysis and a spurious sense of
      comprehensiveness. By privileging proximate risk factors, it fails to address the
      wider environment of the post-reform political economy that ultimately governs
      population movement and put migrant workers at risk of health problems. This
      paper submits that a critical examination of this sanitised biopsychosocial
      paradigm will enliven biomedical research as well as augment its impact on policy
      development in China.

PMID- 9783868
TI  - Mexican use of lead in the treatment of empacho: community, clinic, and
      longitudinal patterns.
AB  - This paper discusses research designed to investigate community, clinic, and
      longitudinal patterns in use of lead as a treatment for empacho, a folk illness
      manifest by gastrointestinal symptoms. The same questionnaire used in a clinic
      based study seven years previously in Guadalajara, Mexico, was used to interview
      a randomly selected community sample: in addition, the study was repeated at the
      same clinic sites that had been studied previously. The goals were to
      investigate: (1) What are community wide prevalences of empacho and use of lead
      based remedies? (2) To what extent are current patterns of use of lead for
      treatment of empacho in clinic-based samples similar to those seven years ago.
      The attributable risk to the population as a whole from use of lead based
      remedies was found to be 11% of the households of Guadalajara. Essentially this
      same estimate was seen for the 1987 and 1994 clinic populations. Interestingly,
      while percentages of lead users have declined since 1987, twice as great a
      percentage of informants reported treating empacho. Other patterns originally
      identified in 1987 persisted in 1994; lead use continues to be associated with
      lower levels of parental education and income.

PMID- 9783869
TI  - Doctor talk and diabetes: towards an analysis of the clinical construction of
      chronic illness.
AB  - During the last two decades the illness narrative has emerged as a popular North
      American literary form. Through poignant stories, well-educated patients have
      recounted their struggle with disabling diseases as well as with the hospitals
      and health care bureaucracies from whom they seek service. However, much less has
      been written about the doctor's narrative construction of chronic diseases either
      in the process of learning medicine or through diagnosing, treating and
      counseling chronically ill patients. Indeed, following Kleinman's lead, the
      physician's narrative has been narrowly viewed as a discourse on the verifiable
      manifestations of pathophysiology. Drawing on contemporary theories of
      storytelling--including the conception of narrative as conversational interaction
      -the present paper argues that doctor narratives are equally complex if quite
      different than patient stories. Indeed, through an analysis of doctor talk
      centering on diabetes mellitus collected in several distinct venues--case
      presentations, narrative interviews and medical consultations--it is argued that
      physician stories not only employ very evocative tropes, but that these stories
      combine didactic, rhetorical and soterological elements in the telling. The
      research was conducted at two, urban family practice training sites in Chicago.

PMID- 9783870
TI  - Social class and health: the puzzling counter-example of British South Asians.
AB  - British South Asians (with ancestry from the Indian subcontinent) provided a
      puzzling exception to the British class gradient in mortality during the 1970s.
      On the assumption that class gradients in health are produced mainly by gradients
      in standard of living, this might be due to a break in the relation of class to
      standard of living (change in class structure), or by a break in the relation of
      standard of living to patterns of health behaviour and health risk (change in
      class lifestyles). Data on these characteristics are available from the West of
      Scotland Twenty-07 Study, where 159 South Asians aged 30-40 (mean age 35) were
      sampled alongside 319 of the general population in Glasgow. As regards changes in
      class structure, results indicate that the underclass thesis, which suggests that
      ethnic minorities are forced into less eligible jobs or into a separate labour
      market or into unemployment, resulting in a standard of living below that of the
      general population, still holds good for British South Asians in categories from
      social class III non-manual downwards. It does not hold good for owners of small
      businesses, where Sikhs and Hindus in particular have a standard of living
      equivalent to general population counterparts. However, prosperity is not
      predictable from levels of education in the subcontinent and from this and other
      signs it appears that a wholesale redistribution of class chances is occurring
      among British South Asians, disrupting inter-and intra-generational continuities
      in the relation between class and standard of living. There is little sign of
      change in class lifestyles, i.e. in the relation between standard of living and
      health behaviour or health risk. As yet, though, the new distribution of standard
      of living is affecting patterns of health behaviour and health risk more strongly
      than symptom experience or chronic illness, suggesting that a class gradient in
      health will re-emerge.

PMID- 9783871
TI  - Cancer truth disclosure by Lebanese doctors.
AB  - Truthful disclosure of cancer diagnosis is still uncommon in some cultures. In
      Lebanon, legislation is permissive of non-disclosure. Physicians choose the
      recourse most agreeable to them. This study's goal was to determine the
      proportion of Lebanese physicians who choose truthful diagnosis disclosure to
      cancer patients and to identify factors affecting their choice. A survey of a
      random sample of Lebanese physicians was conducted to determine the proportion of
      those who prefer truthful diagnosis disclosure to cancer patients and to identify
      factors affecting that choice. The survey involved 268 participants representing
      10% of all physicians practicing in specialties with potential contact with
      cancer cases in the Greater Beirut area. It was completed by 212 (79%), of whom
      47% would usually tell the patient about cancer. Disclosure preference was not
      associated with gender, location of medical training, rate of patient contact or
      teaching activities. It was associated with longer clinical practice and with
      specialties outside primary care. Most participants were open to changing their
      policies and considered the patient's desire to know, compliance with treatment
      and the patient's profession as a physician as most influencing in their choice
      of disclosure. Exploring the Lebanese public predicament regarding disclosure
      seems necessary.

PMID- 9783872
TI  - Probabilities and health risks: a qualitative approach.
AB  - Health risks, defined in terms of the probability that an individual will suffer
      a particular type of adverse health event within a given time period, can be
      understood as referencing either natural entities or complex patterns of belief
      which incorporate the observer's values and knowledge, the position adopted in
      the present paper. The subjectivity inherent in judgements about adversity and
      time frames can be easily recognised, but social scientists have tended to accept
      uncritically the objectivity of probability. Most commonly in health risk
      analysis, the term probability refers to rates established by induction, and so
      requires the definition of a numerator and denominator. Depending upon their
      specification, many probabilities may be reasonably postulated for the same
      event, and individuals may change their risks by deciding to seek or avoid
      information. These apparent absurdities can be understood if probability is
      conceptualised as the projection of expectation onto the external world.
      Probabilities based on induction from observed frequencies provide glimpses of
      the future at the price of acceptance of the simplifying heuristic that
      statistics derived from aggregate groups can be validly attributed to individuals
      within them. The paper illustrates four implications of this conceptualisation of
      probability with qualitative data from a variety of sources, particularly a study
      of genetic counselling for pregnant women in a U.K. hospital. Firstly, the
      official selection of a specific probability heuristic reflects organisational
      constraints and values as well as predictive optimisation. Secondly,
      professionals and service users must work to maintain the facticity of an
      established heuristic in the face of alternatives. Thirdly, individuals, both lay
      and professional, manage probabilistic information in ways which support their
      strategic objectives. Fourthly, predictively sub-optimum schema, for example the
      idea of AIDS as a gay plague, may be selected because they match prevailing
      social value systems.

PMID- 9783873
TI  - The sick building syndrome: a diagnostic dilemma.
AB  - Sick building syndrome (SBS) is usually defined as an increased occurrence of non
      specific symptoms among populations in determined buildings. This definition
      differs from those of other medical syndromes in that it refers to a system (a
      building inclusive of its population) rather than to a clinical state in a single
      individual. Such a definition should make the term SBS impossible to use as a
      diagnosis applied to individual persons. In spite of this, it is often used in
      this way, and the aim of the article is to discuss problems with this practice.
      It is a case study based on an office building with long-standing building
      related health problems. Information concerning the building and its inhabitants
      comes from a large number of separate documentary sources. The study demonstrates
      that the diagnostic use of SBS suffers from serious weaknesses. It is proposed
      that such diagnostics could even have a normative force serving to maintain and
      reinforce building-related, non-specific health problems. It is therefore
      suggested that the term sick building syndrome should be abandoned.

PMID- 9783874
TI  - The meaning and management of neuroleptic medication: a study of patients with a
      diagnosis of schizophrenia.
AB  - The meaning of medication and the way in which people use medicines has been the
      focus of a number of studies in recent years. However, there has been little
      attention directed to the meaning and management of neuroleptic medication by
      people who have received a diagnosis of schizophrenia. This topic is highly
      relevant to policy because of the central role given to neuroleptics in
      contemporary mental health and community care services. Using data from in-depth
      interviews with people with a diagnosis of schizophrenia we explore patients
      reasons for taking neuroleptics and the ways in which patients self-regulate
      their medication. The data suggest that the main utility of taking neuroleptic
      medication is to control specific symptoms and to gain personal control over
      managing symptoms. The costs of taking medication were side-effects which at
      times equalised or outweighed the positive gains of the neuroleptic medication.
      Patient accounts suggest that everyday medication practices are to a significant
      degree related to a policy context which stresses the need to survey and control
      the behaviour of people living in the community and the wider meaning and
      symbolic significance that schizophrenia has for patients in their everyday
      lives. For this reason, self regulatory action in this group of patients tends to
      be less evident and the threat of external social control greater than patients
      taking medication for other chronic conditions. The findings suggest the need to
      develop a collaborative patient-centred model of medication management for
      patients diagnosed with schizophrenia.

PMID- 9783875
TI  - Accidents, assaults, and marital status.
AB  - Marriage may reduce the risk of accidents and assaults by promoting social
      control of health behavior. This study examines the impact of marital status on
      non-fatal accidents and assaults in young British women. Data is drawn from a
      large cohort study of the people born in 1958. Rate ratios of overall and
      specific incidence of non-fatal accidents and assaults are determined by negative
      binomial regression, with adjustment for socio-economic and behavioral
      confounders. The null hypothesis of no association between marital status and
      incidence of non-fatal accidents and assaults is rejected. It is suggested that,
      independent of parental status, more exposure to marriage and less exposure to
      marital dissolution may reduce accidents and assaults.

PMID- 9783876
TI  - Class differences in the food rules mothers impose on their children: a cross
      national study.
AB  - Many studies indicate that children in middle-class families have healthier
      eating habits than children in lower class families. Class differences in food
      rules, which parents and especially mothers impose on their children, may
      underlie these social inequalities in food consumption. The present study uses
      education as a classifying variable and analyses whether mothers with higher
      education prescribe more "healthy" foodstuffs for their children and whether they
      restrict more "unhealthy" food items than less educated mothers. Moreover, the
      study examines whether higher class mothers consider health aspects more often
      and the preferences of their family members less often in their choice of food,
      and whether class differences in these considerations explain class differences
      in food rules. To answer these questions, questionnaires on the food practices of
      849 women living in middle-class or lower class districts in Maastricht (the
      Netherlands), Liege (Belgium) and Aachen (Germany) were collected and analysed.
      The majority of mothers in each city prescribed primarily foods that were served
      at dinner like meat and vegetables, and most mothers limited their children's
      consumption of sweet foods, soft drinks and snacks. Higher class mothers
      restricted more foods, but prescribed as many food items as their lower class
      counterparts. Class differences in the number of restricted foods were partly,
      but not completely, explained by class differences in health and taste
      considerations. Despite national variations in dietary habits and possibly in the
      education of children, class differences in food rules and the explanatory power
      of health and taste considerations were comparable in the three cities.

PMID- 9783877
TI  - From reviving the living to raising the dead; the making of cardiac
      resuscitation.
AB  - Cardiac arrest (the process of the heart ceasing to beat) and cardiac
      resuscitation (the attempt to restart the heart) were created in the surgical
      theatres of the early to middle twentieth century, in response to the cardiac
      arrests which were being caused by the "theatre" doctors themselves. These
      patients were young and healthy (a consequence of the preselection surgery
      involves), cardiac resuscitation was trying to revive the living. The paper
      explores the intimate relationship between cardiac arrest and cardiac
      resuscitation. By the use of historical and Latourian sociological analysis the
      paper also reveals how cardiac resuscitation was made into the emblematic medical
      event it is today, a process which has been so complete that it has become, in
      many senses, an "obligatory passage point to death", that is, in order to die one
      must pass through cardiac resuscitation. The outcome of this is the changed
      nature of cardiac resuscitation, no longer attempting to revive the living,
      cardiac resuscitation now attempts to raise the dead and dying, and at this it
      fails. Despite the remarkable success of cardiac resuscitation as a fact, the
      paper argues that it is a failure as a technique, paradoxically the more
      successful a fact it became, the more it failed as a procedure. The paper
      explains this apparent contradiction and the resistance to anomalies, by showing
      how cardiac resuscitation was created simultaneously inside and outside medical
      science, from its very start being a social and scientific fact with a vast
      network of stabilising allies.

PMID- 9783878
TI  - The meaning of patient satisfaction: an explanation of high reported levels.
AB  - The social policy background to the proliferation of patient satisfaction surveys
      is a desire for increased patient representation and participation. Within this
      context, it is assumed that satisfaction surveys embody patients' evaluations of
      services. However, as most surveys report high satisfaction levels, the
      interpretation of satisfaction as the outcome of an active evaluation has been
      called into question. The aim of this study is to identify whether and how
      service users evaluate services. This was made possible through unstructured in
      depth interviews with users of mental health services and through more structured
      discussion around their responses on a patient satisfaction questionnaire (CSQ
      18B) whose psychometric properties has been well documented. Twenty-nine people
      with current or recent contact with mental health services within the British
      National Health Service were interviewed. The data revealed that service users
      frequently described their experiences in positive or negative terms. However,
      the process by which these experiences were transformed into "evaluations" of the
      service was complex. Consequently, many expressions of "satisfaction" on the CSQ
      18B hid a variety of reported negative experiences. An explanation for this lack
      of correspondence is outlined.

PMID- 9783880
TI  - The fake patient: a research experiment in a Ghanaian hospital.
AB  - The authors report on a research experiment involving the admission of one of
      them as a pseudo-patient in a rural Ghanaian hospital. The experiment was meant
      to assess the feasibility of carrying out unobtrusive participant observation in
      a hospital setting. Practical, methodological and ethical implications are
      discussed.

PMID- 9783879
TI  - Spousal caregivers' activity restriction and depression: a model for changes over
      time.
AB  - In this paper we examine the effects of increasing as well as decreasing
      caregiving demands on depressive symptomatology. In addition, we focus on spousal
      caregivers' activity restriction as an explanatory mechanism for changes in
      depressive symptomatology in the caregiving context. Two databases are used to
      answer our research questions. An increase of caregiving demands is assessed in
      study 1, which includes prospective data on 127 spousal caregivers of stroke, hip
      fracture, congestive heart failure and myocardial infarction patients. A decrease
      of caregiving demands is examined in study 2, which includes prospective data on
      110 spousal caregivers of bypass operation patients. The results generally
      support the hypothesis that an increase in caregiving demands results in
      increased depressive symptomatology, while a decrease in caregiving demands
      reduces depressive symptomatology. The results also support the notion of
      activity restriction as a critical mediator of changes in depressive symptoms.
      Cross-sectionally it mediates the association between caregiving and depressive
      symptomatology, and longitudinally it contributes to changes in depressive
      symptomatology in both samples.

PMID- 9783881
TI  - Becoming a doctor--was it the wrong career choice?
AB  - The aim of the study was to investigate the social background of physicians, the
      reasons that influenced doctors to enter medicine, and the association between
      those reasons and satisfaction in career choice of young Finnish doctors. An
      extensive postal questionnaire was mailed to a random sample of 2632 young
      Finnish doctors in 1988 and to 2332 doctors in 1993. We found out that majority
      of the respondents reported that interest in people, a wide range of job
      opportunities, the fact that medicine is a highly-appreciated profession, and
      success at school had influenced their decision to enter medicine quite a lot or
      very much. In 1988, 8% and in 1993, 7% of the respondents reported that interest
      in people had not influenced their career choice at all or only slightly. More
      women than men were influenced quite a lot or very much by factors like interest
      in people, success at school and vocation, meaning the lifelong calling to
      physicians' profession. A total of 22% of respondents would not enter medicine
      again. Vocation, interest in people and wide range of job opportunities were
      significantly more rarely mentioned as an important career choice motive by these
      respondents. It seems that interest in human beings and vocation are important to
      would-be doctors, and also help them to get along in the physicians' profession.
      Medical schools should develop their curricula towards more humanistic medicine
      in order to maintain their students' interest in people.

PMID- 9783882
TI  - Accelerated radiotherapy with carbogen and nicotinamide (ARCON) for laryngeal
      cancer.
AB  - BACKGROUND AND PURPOSE: Tumor hypoxia and tumor cell repopulation are known
      factors determining radiation response. Accelerated radiotherapy as a method to
      counteract cellular repopulation was combined with carbogen (95% O2 + 5% CO2)
      breathing and oral administration of nicotinamide as a means to improve tumor
      perfusion and oxygenation. The feasibility, toxicity and clinical effectiveness
      of this approach as a voice-preserving treatment for carcinoma of the larynx was
      assessed in a prospective study. PATIENTS AND METHODS: Sixty-two patients with
      stage III-IV laryngeal carcinoma were treated with a schedule of accelerated
      radiotherapy. The total radiation dose to the primary tumor was 64 Gy and that to
      the metastatic nodes was 68 Gy delivered in fractions of 2 Gy over 35-37 days.
      Radiotherapy was combined with carbogen breathing in the initial 11 patients and
      with both carbogen and nicotinamide administration in the subsequent 51 patients.
      RESULTS: After a median follow-up of 24 months, the actuarial local control rate
      at 2 years was 92%. This is higher than any previous report in the literature for
      this category of patients. Five patients had a local tumor recurrence and
      underwent laryngectomy. There was one regional recurrence. Including salvage
      surgery the loco-regional control rate was 100%. Four patients developed distant
      metastases and died. The actuarial overall survival rate at 2 years was 85%.
      Toxicity was increased relative to conventional radiotherapy but was considered
      as acceptable. One patient underwent laryngectomy for radiation-induced cartilage
      necrosis. CONCLUSION: These preliminary results indicate that advanced laryngeal
      cancer can be controlled in a high proportion of patients when treated with
      accelerated radiotherapy combined with carbogen and nicotinamide. This approach
      offers excellent possibilities for larynx preservation.

PMID- 9783883
TI  - Pharmacokinetics of nicotinamide in cancer patients treated with accelerated
      radiotherapy: the experience of the Co-operative Group of Radiotherapy of the
      European Organization for Research and Treatment of Cancer.
AB  - BACKGROUND: The EORTC has initiated studies to combine nicotinamide with carbogen
      in accelerated fractionation schedules (ARCON), since for some tumour types,
      acute and chronic hypoxia as well as treatment protraction may prejudice the
      outcome of radiotherapy. The tolerable dose of nicotinamide and the optimal
      interval for administration need to be ascertained. AIM: Full pharmacokinetic
      profiles of nicotinamide concentrations in plasma were analyzed repeatedly in 15
      patients to determine the inter- and intra-patient variability in peak plasma
      concentrations and the optimum times for administering nicotinamide as a
      radiosensitizer. METHODS: Nicotinamide (Nicobion) was administered in tablet form
      to patients with advanced head and neck and non-small cell lung carcinomas. A
      standard 6 g dose was given regardless of body weight after an overnight fast and
      at least 30 min before breakfast. In 15 patients, blood samples were taken prior
      to and 1, 2, 4, 6, 8, 12 and 24 h after administration of the drug. This full
      profile was determined on two to four occasions for the head and neck cancer
      patients and on two occasions for the lung cancer patients. For each profile, the
      maximum concentration of nicotinamide (Cmax), time to peak plasma concentration
      (Tmax), elimination half-lives (t1/2) and area under the curve (AUC) were
      determined. Compliance was recorded and nausea and vomiting were graded on a 0-3
      scale. Complete profiles of the five major metabolites were also obtained.
      RESULTS: In the 48 complete sets of blood samples, peak plasma concentrations
      ranged from 787 to 2312 nmol/ml with a median value of 1166 nmol/ml. The peak
      plasma concentration was achieved at 1 h in only 54% of the pharmacokinetic
      profiles, but at this time 92% of the profiles had already exceeded the target
      concentration of 700 nmol/ml, the level required in the mouse for tumour
      radiosensitization. The median t1/2 for all 15 cases was 9.3 h, with minimum and
      maximum values of 4.2 and 26.8 h. The highest concentrations of nicotinamide
      metabolites were found to be the N-oxide, 2-pyridone and 1-methylnicotinamide.
      The toxicity (nausea and vomiting) was scored and found not to be correlated with
      any of the pharmacokinetic parameters. CONCLUSIONS: The plasma concentrations
      considered necessary to radiosensitize can easily be exceeded with a dose of 6 g
      taken as 12 x 500 mg in tablet form; 700 nmol/ml was achieved in all patients and
      apparently would have been achieved in most even with a considerable reduction in
      dose. An adequate time between administration and radiotherapy appeared to be 1 h
      with this drug formulation for 92% of the profiles.

PMID- 9783884
TI  - Lack of perfusion enhancement after administration of nicotinamide and carbogen
      in patients with glioblastoma: a 99mTc-HMPAO SPECT study.
AB  - BACKGROUND: Nicotinamide (NAM) and carbogen both have been shown to enhance the
      radiation effect in rodent tumour models and are currently being tested in
      clinical trials. These agents have demonstrated to act against hypoxia and one of
      their underlying mechanisms could be an increase of tumour blood perfusion.
      PURPOSE: To analyse the effect of both agents on normal brain perfusion and
      tumour perfusion in patients with glioblastoma. MATERIALS AND METHODS: Nineteen
      patients with glioblastoma were studied with 99mtechnetium
      hexamethylpropyleneamine oxime single photon emission computed tomography (99mTc
      HMPAO SPECT) before and after administration of carbogen and/or NAM. Another six
      patients were studied with the same procedure but without any flow modulator and
      were used as controls. RESULTS: Although the variations between patients were
      large, no significant enhancement in mean tumour and normal brain perfusion could
      be demonstrated with NAM or carbogen compared to the control patients. Also no
      consistent changes in the mean perfusion ratio between tumour and surrounding
      normal brain were found, suggesting an absence of a selective perfusion effect.
      CONCLUSIONS: No significant influence of carbogen and/or NAM on tumour perfusion
      and normal brain perfusion could be detected with SPECT in patients with
      glioblastoma.

PMID- 9783885
TI  - The effect of combined nicotinamide and carbogen treatments in human tumour
      xenografts: oxygenation and tumour control studies.
AB  - BACKGROUND AND PURPOSE: This was an investigation to study the effect of giving
      carbogen and nicotinamide (CON) on pO2 and the radiation response of human
      xenografted tumours. MATERIALS AND METHODS: The human xenografts were two
      sarcomas (ENE2 and ES3) and a glioblastoma (HTZ17). Nicotinamide (500 mg/ kg,
      i.p.) was administered 60 min before PO2 measurements and irradiation, while
      carbogen was given for 5 min before and during these treatments. Tumour pO2 was
      measured with an Eppendorf electrode and radiation response was assessed by local
      tumour control following irradiation with 10 daily fractions. RESULTS: All three
      xenografts were found to be poorly oxygenated (about 80% of all pO2 values were <
      or =2.5 mmHg). CON treatment improved the oxygenation status in all three tumours
      such that 65, 52 and 71% of the pO2 values were < or =2.5 mmHg in ENE2, ES3 and
      HTZ17, respectively. However, only in ES3 was this decrease significant. The
      TCD50 doses for all tumours were around 52-54 Gy. No significant improvement was
      seen with CON in ENE2 (TCD50 = 48 Gy) and HTZ17 (TCD50 = 56 Gy), but for the ES3
      xenograft a significant decrease to 42 Gy was found. CONCLUSIONS: The three
      tumours used in this study appeared to show the same level of hypoxia as measured
      both by pO2 and radiation response. However, only one tumour showed a significant
      improvement after CON treatment, suggesting that not all hypoxic human tumours
      might benefit from this type of therapy.

PMID- 9783887
TI  - Changes in tumor oxygenation during combined treatment with split-course
      radiotherapy and chemotherapy in patients with head and neck cancer.
AB  - PURPOSE: To evaluate the changes in tumor oxygenation during definitive split
      course radiochemotherapy in locally advanced head and neck cancer (lymph nodes
      and primaries). MATERIALS AND METHODS: Twenty-four patients with locally advanced
      head and neck cancer were investigated pretherapeutically and during a defined
      course of radiochemotherapy (RCTh) with a total dose of 70 Gy given in 35
      fractions over 9 weeks (2-week break after 30 Gy). In weeks 1 and 6, the patients
      received chemotherapy (5 FU and mitomycin C) concomitant with irradiation. The
      oxygen partial pressure measurements were carried out using polarographic needle
      probes in combination with a microprocessor-controlled device (pO2
      histograph/KIMOC). Times of measurements were before therapy, at the end of week
      3 (30 Gy), after a 2-week break (30 Gy) and at the end of therapy if measurable
      lesion was found (70 Gy). RESULTS: There was a significant reduction in the
      median pO2 (P < 0.005, n = 18) and an increase in the hypoxic fraction (defined
      as the percentage of pO2 values of <5 mm Hg) after application of 30 Gy (P <
      0.05, n = 18). This effect was partially reversed at the end of the 2-week break.
      During the break an increase in the median PO2 (P = 0.05, n = 12) and a decrease
      in the hypoxic fraction could be observed. Towards the end of therapy (70 Gy) a
      significant decrease (P = 0.02, n = 13) in the median pO2 occurred. Corresponding
      to this, the hypoxic fraction increased during the last 4 weeks of therapy (P =
      0.06, n = 13). CONCLUSION: Statistically significant changes in oxygenation in
      locally advanced head and neck cancer were found during a split-course
      radiochemotherapy. This information was obtained in a homogenous group of
      patients under well-defined therapeutic conditions. The decrease in the tumor
      oxygenation status at doses of 30 and 70 Gy are important findings because they
      are in contrast to the concept of continuous improvement of the oxygenation
      status during fractionated radiotherapy.

PMID- 9783886
TI  - Oxygenation predicts radiation response and survival in patients with cervix
      cancer.
AB  - BACKGROUND AND PURPOSE: Hypoxia appears to be an important factor in predicting
      tumor relapse following radiation therapy. This study measured oxygenation prior
      to treatment in patients with cervix cancer using a polarographic oxygen
      electrode to determine if oxygenation was an important prognostic factor with
      regard to tumor control and survival. MATERIALS AND METHODS: Between May 1994 and
      June 1997, 74 eligible patients with cervix cancer were entered into an ongoing
      prospective study of tumor oxygenation prior to primary radiation therapy. All
      patients were evaluated with an Eppendorf oxygen electrode during examination
      under anesthesia. Oxygenation data are presented as the hypoxic proportion,
      defined as the percentage of pO2 readings of <5 mm Hg (abbreviated as HP5).
      RESULTS: The HP5 ranged from 2 to 99% with a median of 52%. With a median follow
      up of 1.2 years, the disease-free survival (DFS) rate was 69% for patients with
      HP5 of < or =50% compared with 34% for those with HP5 of >50% (log-rank P =
      0.02). Tumor size above and below the median of 5 cm was also significantly
      related to DFS (P = 0.0003) and patients with bulky hypoxic tumors had a
      significantly lower DFS (12% at 2 years) than either bulky oxygenated or non
      bulky oxygenated or hypoxic tumors (65%, P = 0.0001). CONCLUSIONS: Hypoxia and
      tumor size are significant adverse prognostic factors in a univariate analysis of
      disease-free survival in patients with cervix cancer. A high risk group of
      patients with bulky hypoxic tumors have a significantly higher probability of
      relapse and death.

PMID- 9783888
TI  - Effect of gap length and position on results of treatment of cancer of the larynx
      in Scotland by radiotherapy: a linear quadratic analysis.
AB  - PURPOSE: This paper reports on the analysis of the effect of the length and
      position of unplanned gaps in radiotherapy treatment schedules. MATERIALS AND
      METHODS: Data from an audit of the treatment of carcinoma of the larynx are used.
      They represent all newly diagnosed cases of glottic node-negative carcinoma of
      the larynx between 1986 and 1990, inclusive, in Scotland that were referred to
      one of the five Scottish Oncology Centres for primary radical radiotherapy
      treatment. The end-points are local control of cancer of the larynx in 5 years
      and the length of the disease-free period. The local control rates at > or =5
      years, Pc were analyzed by log linear models and Cox proportional hazard models
      were used to model the disease-free period. RESULTS: Unplanned gaps in treatment
      are associated with poorer local control rates and an increased hazard of a local
      recurrence through their effect on extending the treatment time. A gap of 1 day
      is potentially damaging but the greatest effect is at treatment extensions of 3
      or more days, where the hazard of a failure of local control is increased by a
      factor of 1.75 (95% confidence interval 1.20-2.55) compared to no gap. The time
      factor for the actual time was imprecisely estimated at 2.7 Gy/day with a
      standard error of 13.2 Gy/day. Among those cases who had exactly one gap
      resulting in a treatment extension of 1 day, there is no evidence that gap
      position influences local control (P = 0.17). The treatment extension as a result
      of the gap is more important than the position of the gap in the schedule.
      CONCLUSIONS: Gaps in the treatment schedule have a detrimental effect on the
      disease-free period. A gap has a slightly greater effect than an increase in the
      prescribed treatment time. Any gap in treatment is potentially damaging. The
      position of the gap in the schedule was shown to be not important.

PMID- 9783889
TI  - Comparison of external radiotherapy, laser microsurgery and partial laryngectomy
      for the treatment of T1N0M0 glottic carcinomas: a retrospective evaluation.
AB  - PURPOSE: The aim of this study was to retrospectively compare the efficacy and
      functional results of three treatment options for T1N0M0 glottic carcinomas
      applied in a single institution. MATERIALS AND METHODS: One hundred six charts of
      patients with biopsy-proven T1N0M0 glottic carcinomas treated between 1979 and
      1995 were reviewed. There were 81 T1a and 25 T1b tumors. Forty-one patients were
      treated by radiotherapy (RT) (median dose of 64 Gy), 34 patients were treated by
      partial laryngectomy (PL) and 31 patients were treated by laser microsurgery (L)
      of which 10 received postoperative RT for positive margins. In 18 patients, a
      perceptual voice rating on a visual scale was performed by the patients
      themselves, three non-speech specialists and two speech therapists. RESULTS: With
      a median follow-up time of 63.5 months, the 5- and 10-year loco-regional control
      probabilities reached 91 and 87%, respectively, without any difference between
      the treatment groups. After salvage laryngectomy, the 5- and 10-year loco
      regional control probabilities reached 97% without any difference between the
      treatment groups. For the whole population, overall survival reached 78 and 62.4%
      at 5 and 10 years, respectively. The actuarial incidence of second primary
      reached 19% at 10 years. Regarding the quality of voice, overall there was a
      trend towards a worse satisfaction index, more hoarseness and more breathiness
      after PL than after L or RT. CONCLUSIONS: Our data suggested that assuming proper
      selection of patients, RT and L yielded similar outcomes and functional results.
      Local recurrence can be adequately salvaged by surgery. On the other hand, PL
      appeared to yield similar loco-regional control probability but with a worse
      quality of voice.

PMID- 9783890
TI  - Long-term cardiac morbidity and mortality in a randomized trial of pre- and
      postoperative radiation therapy versus surgery alone in primary breast cancer.
AB  - BACKGROUND AND PURPOSE: Some types of radiation therapy have been associated with
      an increased risk of cardiac mortality and morbidity in patients with early-stage
      breast cancer. A relationship has been observed between cardiac radiation dose
      volume and the level of excess risk of cardiac mortality. However, relatively few
      data are available on the morbidity from myocardial infarction associated with
      adjuvant radiotherapy. PATIENTS AND METHODS: From 1971 to 1976, a total of 960
      patients with operable breast cancer were randomly allocated to preoperative
      radiation therapy, postoperative radiation therapy or to surgery alone. A
      previous analysis of the cardiac dose-volumes with the treatment techniques used
      in the trial indicated that the irradiated patients could roughly be divided into
      three groups. Information on the number of myocardial infarctions was obtained
      through computerized record linkage with a population-based registry of
      myocardial infarctions in Stockholm County. Information on cause-specific
      mortality was obtained from the Swedish Cause-of-Death Registry. The median
      follow-up was 20 years (range 17-23 years). RESULTS: A total of 58 patients
      developed an acute myocardial infarction during the period of follow-up. The
      number of myocardial infarction cases was not significantly different between the
      three treatment groups. When analyzed according to estimated cardiac radiation
      dose-volumes, patients in the highest dose-volume subgroup exhibited a hazard of
      myocardial infarction of 1.3 (95% CI 0.7-2.6) relative to that of the surgical
      controls, whereas the corresponding relative hazard for the intermediate and low
      dose-volume subgroups was below unity. Data on death due to cardiovascular
      disease showed that patients in the high dose-volume group exhibited a hazard of
      2.0 (95% CI 1.0-3.9, P = 0.04) relative to that of the surgical controls.
      Concerning death due to ischemic heart disease, the relative hazard for the same
      subgroup was 2.5 (95% CI 1.1-5.7, P = 0.03). The difference between the groups
      was established after 4-5 years. The cumulative incidence curves continued to
      diverge up to about 10-12 years. No further divergence appeared after 12 years,
      but the number of events was low. CONCLUSIONS: This analysis confirms and extends
      previous results from the trial. Cardiac mortality was positively correlated with
      the cardiac dose-volume. Patients receiving high dose-volumes exhibited an
      increased mortality of ischemic heart disease, but not of myocardial infarction,
      which implies another mechanism, e.g. radiation-induced microvascular damage to
      the heart.

PMID- 9783891
TI  - Outcome in breast cancer managed without an initial axillary lymph node
      dissection.
AB  - PURPOSE: The role of an elective axillary lymph node dissection (AxLND) in the
      initial management of patients with early stage breast cancer has recently become
      controversial. The objective of this current study is to review the reasons as to
      why patients from a single institution were managed without an initial AxLND and
      their outcome in terms of survival and recurrence rates. MATERIALS AND METHODS: A
      retrospective analysis was conducted on 126 women referred to the Princess
      Margaret Hospital with the diagnosis of breast cancer who did not undergo an
      initial AxLND. RESULTS: The median age of this population was 69 years, with the
      vast majority (93%) being post-menopausal. Fifty-seven patients had T1 tumors and
      the remainder had T2-3 tumors. Adjuvant radiation therapy to the breast was
      administered to 65 patients and systemic adjuvant treatment was administered to
      24 patients. In approximately one-third of these cases, the reasons cited for not
      performing an AxLND were related to the patient's age, a medical
      contraindication, or the patient's choice. The 5-year actuarial cause-specific
      survival was 92%; the local breast relapse-free rate (RFR) was 85% and the
      axillary RFR was 86%. No patients in this study experienced debilitating symptoms
      from their axillary disease. Only 16 patients underwent a subsequent AxLND, with
      the lymph nodes being pathologically uninvolved in six of these patients.
      CONCLUSION: This study supports the concept that. in selected patients, adopting
      an approach of a delayed AxLND does not appear to compromise the patients'
      outcome, with only 13% of patients requiring a subsequent AxLND.

PMID- 9783893
TI  - The relationship between biochemical failure and time to nadir in patients
      treated with external beam therapy for T1-T3 prostate carcinoma.
AB  - PURPOSE AND BACKGROUND: To determine a prostatic-specific antigen (PSA) nadir
      value and time to nadir that predict a high probability of freedom from
      biochemical failure in men treated with external beam therapy for prostate
      cancer. MATERIALS AND METHODS: Between January 1990 and March 1994, 228 men with
      T1-T3 adenocarcinoma of the prostate received a radical course of external beam
      irradiation with no prior or adjuvant hormonal therapy. All men had pre- and post
      treatment serum PSA evaluations, and were followed up for at least 24 months, to
      ensure PSA nadir was reached. Biochemical failure was defined as three successive
      post-treatment rises in serum PSA, regardless of the magnitude of elevation.
      RESULTS: Overall, 4-year biochemical disease-free survival (BDFS) was 42%. PSA
      nadir was predictive of subsequent BDFS. For those whose serum PSA nadir was < or
      =1 ng/ml, 4-year BDFS was 70%, versus 12% for those with serum PSA nadir > 1
      ng/ml (P = < 0.001). The 4-year BDFS for patients with time to nadir < or =1
      year, was 28%, versus 58% for those with time to nadir > 1 year (P < 0.001). For
      patients with PSA nadir < or =1 ng/ml, 4-year BDFS was 75% for those with time to
      nadir > 1 year, versus 61% for those with time to nadir < or =1 year (P < 0.021).
      In multivariate analysis, PSA nadir(< or =1 ng/ml versus >1 ng/ml, and time to
      nadir (< or =1 year versus > year) were independent predictors of BDFS alone with
      pre-treatment PSA and Gleason score. CONCLUSION: Only those who achieved PSA
      nadir < or =1 ng/ml following external beam therapy have a favourable chance of
      lasting biochemical disease control, while those with nadir > 1 ng/ml have a high
      subsequent failure rate. The prognosis is better in patients with late time to
      nadir. In addition to PSA nadir, time to nadir, pretreatment PSA, and Gleason
      score were of independent prognostic significance.

PMID- 9783892
TI  - High-dose rate interstitial with external beam irradiation for localized prostate
      cancer--results of a prospective trial.
AB  - PURPOSE: A prospective phase II trial was carried out to test the feasibility and
      effectiveness of a combined interstitial with external beam radiotherapy approach
      for localized prostate cancer. MATERIALS AND METHODS: Between October 1992 and
      December 1994, 82 evaluable patients were treated. T2 and T3 tumours, according
      to the AJCC classification system of 1992, were found in 21 and 61 cases,
      respectively. The median follow-up was 24 months; three patients were lost during
      follow-up. All of the patients were pathologically proven to be node-negative by
      laparoscopic node dissection of the fossa obturatoria region. A dose of 9 Gy a
      week was prescribed during the first and second weeks of treatment (10 Gy each
      week from October 1992 to December 1993) interstitially with high-dose rate
      Iridium-192 brachytherapy to the prostate and tumour extension beyond the
      capsule. External beam four-field box irradiation was then given to the prostate
      to a dose of 45 Gy/25 fractions (40 Gy/20 fractions from October 1992 to December
      1993). RESULTS: Before starting treatment, a PSA value of > or =10 ng/ml was
      found in 64.6% (53/82) of patients with a median PSA of 14.0 ng/ml. The median
      PSA 3, 12 and 24 months after completion of therapy was 1.20, 0.78 and 0.70
      ng/ml, respectively. The PSA value was < 1.0 ng/ ml in 52.9% of patients at 2
      years. Negative punch biopsies 12 and 24 months after therapy were observed in
      69.8% (44/63) and 73. 1% (38/ 52) of patients, respectively. A positive biopsy
      combined with a PSA value of > 1.0 ng/ml was considered as local failure. The
      local tumour control rate was 79.5% at 2 years. Acute side-effects were not
      increased relative to external beam irradiation alone. Severe side-effects were
      observed in three patients (two of the three patients had additional risk factors
      (colitis ulcerosa and diabetes mellitus)); they developed rectourethral fistulae
      requiring colostomy after biopsies from the anterior rectal wall. CONCLUSION: The
      described method is feasible and well tolerable. The three complications observed
      were not caused by irradiation alone. Biopsies from the anterior rectal wall
      after definitive high-dose radiotherapy for prostate cancer have to be seen as
      obsolete. The rate of negative prostate biopsies of 73.1% after 24 months
      represents an encouraging result.

PMID- 9783894
TI  - Re-irradiation for locally recurrent nasopharyngeal carcinoma.
AB  - Since 1989, 17 patients have undergone re-irradiation for locally recurrent
      nasopharyngeal cancer (NPC). The dose currently administered externally is 39.6
      Gy in 36 fractions (BID) followed by an intracavitary boost (15-20 Gy). Disease
      persisted in five out of five patients treated palliatively. Eleven of 12
      patients treated with curative intent achieved local control.

PMID- 9783895
TI  - Sharpening the penumbra of high energy electron beams with low weight narrow
      photon beams.
AB  - BACKGROUND AND PURPOSE: High energy (20-50 MeV) electron beams, available from
      the MM50 Racetrack Microtron, can be used for the treatment of deep-seated
      tumors. A disadvantage is the increasing penumbra width as a function of depth.
      By the addition of a narrow (typically 1 cm wide) photon beam near the field
      edge, the 50-90% penumbra width of the electron beam is reduced, yielding a
      significantly increased effective field size. MATERIALS AND METHODS: For
      rectangular electron beams in a water phantom (energies 25 and 40 MeV, field
      sizes 5 x 5-15 x 15 cm2) a computer program was used to optimize the photon beam
      parameters (position, weight and width) to obtain a combined beam with the
      sharpest penumbra at the optimization depth and a beam flatness within certain
      constraints. The study furthermore included penumbra sharpening of an irregular
      multileaf collimator-shaped field. RESULTS AND CONCLUSION: At optimization depths
      near R90, photon beam addition reduces the penumbra width by 40-50% (from 15-20
      mm to 8-10 mm). Beam flatness at the optimization depth is within +/-5% and hot
      spots are < or =120% for all depths. By the addition of narrow photon beams
      around the rectangular or irregular field, the electron field width can be
      reduced by 1-3 cm, while the effective field size is maintained.

PMID- 9783896
TI  - Are hypoxic cells critical for the outcome of fractionated radiotherapy in a slow
      growing mouse tumor?
AB  - PURPOSE: To investigate the significance of hypoxic cells, reoxygenation and
      repopulation for the outcome of fractionated radiotherapy of a slow-growing
      subline of a murine fibrosarcoma and to compare the results with those previously
      obtained from the original fast-growing tumor. MATERIALS AND METHODS: A slow
      growing subline, 457-O, was obtained among the tumors that recurred after a
      single irradiation to the third generation isotransplants of a mouse
      fibrosarcoma, FSa-II. The single cell suspensions were transplanted into the
      mouse foot and when the tumors reached an average diameter of 4 mm, they were
      subjected to one to 20 equal daily y-ray doses given in air (A) or under hypoxic
      conditions (H). The TCD50 (50% tumor control radiation dose) was calculated
      according to the tumor control frequency within 180 days. The linear-quadratic
      plus time model was fitted to these data by logistic regression analysis.
      RESULTS: The volume doubling time of the 457-O tumors was approximately 2.2 times
      slower than that of the original FSa-II tumors. The TCD50(H) (single dose) was
      52.3 Gy and increased with an increasing number of fractions to a TCD50(H) (20
      doses) of 90.8 Gy. This increase of 38.5 Gy was much smaller than that of 149 Gy
      for the original FSa-II. The TCD50(A) (single dose) and TCD50(A) (20 doses) were
      41.3 and 50.6 Gy, respectively. This small difference of 9.3 Gy contrasted with a
      significant increase of 52.9 Gy for the FSa-II. DISCUSSION: These results
      suggested no repopulation of 457-O tumor clonogens during the course of up to 20
      daily doses, while the original FSa-II tumor cells repopulated substantially.
      Hypoxic clonogens in the slow-growing tumor reoxygenated but some fractions
      remained critical. CONCLUSION: The present data together with those obtained from
      the fast-growing FSa-II suggested that hypoxic clonogens were critical for the
      outcome of fractionated radiotherapy. Repopulation was insignificant in this slow
      growing tumor during five to 20 daily doses.

PMID- 9783898
TI  - Antioxidant-sensitive shortening of ventricular action potential in hyperthyroid
      rats is independent of lipid peroxidation.
AB  - The effects of substances able to reduce peroxidative processes on thyroid
      hormone-induced electrophysiological changes in ventricular muscle fibres were
      examined. For this study, 60 day old euthyroid and hyperthyroid rats were used.
      One group of hyperthyroid rats was untreated and the others were treated with
      vitamin E, N-acetylcysteine, and cholesterol, respectively. Hyperthyroidism was
      elicited by 10 day treatment with daily i.p. injections of triiodothyronine (10
      microg/100 g body weight). Vitamin E and N-acetylcysteine were administered for
      10 days by daily i.m. injections (20 mg/100 g body weight) and daily i.p.
      injections (100 mg/100 g body weight), respectively. Cholesterol was administered
      by cholesterol-supplemented diet (4%) from day 30. Hyperthyroidism induced a
      decrease in the whole antioxidant capacity and an increase in both lipid
      peroxidation and susceptibility to oxidative stress. Vitamin E and N
      acetylcysteine administration to hyperthyroid rats led to reduction in lipid
      peroxidation and susceptibility to oxidative stress and to increase in
      antioxidant level, while the diet addition of cholesterol decreased lipid
      peroxidation but did not modify the other parameters. The hyperthyroid state was
      also associated with a decrease in the duration of the ventricular action
      potential recorded in vitro. The vitamin E and N-acetylcysteine administration
      attenuated the thyroid hormone-induced changes in action potential duration,
      which was however, significantly different from that of the euthyroid rats. In
      contrast, cholesterol supplementation did not modify the electrical activity of
      hyperthyroid heart. These results demonstrate that the triiodothyronine effects
      on ventricular electrophysiological properties are mediated, at least in part,
      through a membrane modification involving a free radical mechanism. Moreover,
      they indicate that the antioxidant-sensitive shortening of action potential
      duration induced by thyroid hormone is likely independent of enhanced
      peroxidative processes in sarcolemmal membrane.

PMID- 9783897
TI  - G protein abnormalities in pituitary adenomas.
AB  - It has been demonstrated that the majority of secreting and nonsecreting adenomas
      is monoclonal in origin suggesting that these neoplasia arise from the
      replication of a single mutated cell, in which growth advantage results from
      either activation of protooncogenes or inactivation of antioncogenes. Although a
      large number of genes has been screened for mutations, only few genetic
      abnormalities have been found in pituitary tumors such as allelic deletion of
      chromosome 11q13 where the MEN-1 gene has been localised, and mutations in the
      gene encoding the alpha subunit of the stimulatory Gs and Gi2 protein. These
      mutations constitutively activate the alpha subunit of the Gs and Gi2 protein by
      inhibiting their intrinsic GTPase activity. Both Gs alpha and Gi2alpha can be
      considered products of protooncogenes (gsp and gip2, respectively) since gain of
      function mutations that activate mitogenic signals have been recognized in human
      tumors. Gsp oncogene is found in 30-40% of GH-secreting adenomas, in a low
      percentage of nonfunctioning and ACTH-secreting pituitary adenomas, in toxic
      thyroid adenomas and differentiated thyroid carcinomas. The same mutations,
      occurred early in embriogenesis, have been also identified in tissues from
      patients affected with the McCune Albright syndrome. These mutations result in an
      increased cAMP production and in the subsequent overactivation of specific
      pathways involved in both cell growth and specific programmes of cell
      differentiation. By consequence, the endocrine tumors expressing gsp oncogene
      retain differentiated functions. The gip2 oncogene has been identified in about
      10% of nonfunctioning pituitary adenomas, in tumors of the ovary and the adrenal
      cortex. However, it remains to be established whether Gi proteins activate
      mitogenic signals in pituitary cells. Since Gi proteins are involved in mediating
      the effect of inhibitory neurohormones on intracellular effectors, it has been
      proposed that in pituitary tumors the low expression of these proteins,
      particularly Gi1-3alpha, may contribute to uncontrolled pituitary cells growth by
      preventing the transduction of inhibitory signals. While by in vitro mutagenesis
      it has been demonstrated that activated mutant of Gq alpha, G12alpha, G13alpha
      and Gz alpha are fully oncogenic, it remains to be proved whether or not these
      abnormalities might naturally occur in human tumors and, in particular, in
      pituitary adenomas.

PMID- 9783899
TI  - Moderate protein restriction during pregnancy modifies the regulation of
      triacylglycerol turnover and leads to dysregulation of insulin's anti-lipolytic
      action.
AB  - Moderate protein restriction throughout pregnancy in the rat leads to relative
      hyperlipidaemia and blunted insulin responsiveness of lipid fuel supply, and
      impairs foetal growth. The present study examined the basis for these changes.
      Isocaloric 8% (vs 20%) protein diets were provided throughout pregnancy. Rats
      were sampled at 19-20 days of gestation. Protein restriction enhanced
      triacylglycerol (TAG) secretion rates (estimated using Triton WR 1339) 1.6-fold
      (P < 0.05) in the post-absorptive state. Insulin infusion (4.2 mU/kg per min)
      decreased plasma TAG concentrations by 33% (P < 0.05) and 48% (P < 0.05) in
      control (C) and protein-restricted (PR) pregnant groups, an effect associated
      with suppression of TAG secretion by 42% (P < 0.05) and 51% (P < 0.01)
      respectively, in the C and PR groups. Since TAG concentrations decline more
      rapidly, while TAG secretion is enhanced, TAG utilisation during
      hyperinsulinaemia is enhanced in the PR group. We evaluated whether these changes
      were associated with dysregulation of lipolysis using adipocytes from two
      abdominal depots (mesenteric and parametrial). Noradrenaline-stimulated glycerol
      release was enhanced in parametrial adipocytes (by 40%; P < 0.05) from PR
      pregnant rats. The anti-lipolytic action of insulin at low concentrations (< or =
      15 microU/ml) was impaired by protein restriction (adipocytes from both depots).
      There was no evidence for altered intra-hepatic regulation of fatty acid (FA)
      disposal at the level of carnitine palmitoyltransferase. Our results demonstrate
      increased post-absorptive production of non-carbohydrate energy substrates (TAG
      and FA) as a consequence of mild protein restriction during pregnancy. These
      adaptations contribute to a homeostatic strategy to reduce the maternal
      requirement for gluconeogenesis from available amino acids, optimising the foetal
      protein supply. Protein restriction also enhances TAG turnover during
      hyperinsulinaemia. This effect is not a consequence of abnormal regulation of
      hepatic lipid metabolism by insulin.

PMID- 9783900
TI  - A new tool for efficient transfection of dog and human thyrocytes in primary
      culture.
AB  - The introduction of exogenous DNA into mammalian cells is commonly used to study
      the functions of gene products. However cells in primary culture are usually
      refractory to most transfection systems. Here we investigated the ability of a
      new lipid formulation, FuGENE 6 transfection reagent, to promote DNA uptake into
      dog and human thyroid cells in primary culture. Gene transfer was monitored by
      the expression of a Green Fluorescent Protein (GFP) reporter gene. We report that
      FuGENE 6 is particularly suited for the transfection of thyroid cells and does
      not interfere with their normal growth. Optimization of the experimental
      conditions, such as DNA amount, DNA/lipid ratio, cell density and incubation with
      the transfection mixture, was achieved by evaluating the percentage of GFP
      expressing cells by FACS analysis. FuGENE 6 allowed us to obtain 8-15% thyrocytes
      expressing the reporter gene which represents an efficiency 100-fold superior to
      other transfection methods.

PMID- 9783901
TI  - Impaired glucose-stimulated insulin release in islets from adult rats
      malnourished during foetal-neonatal life.
AB  - Poor foetal and neonatal nutrition may impair normal pancreatic beta-cell
      development and predispose to diabetes in later life. We investigate here the
      nature of the pancreatic beta-cell dysfunction in sucrose-fed adult offspring
      malnourished during the foetal-neonatal period and examine glucose metabolism and
      the generation of signals involved in the secretory mechanism. In islets from
      sucrose-fed previously malnourished rats, rates of glucose utilisation
      (production of 3H2O) and oxidation (production of 14CO2), at 2, 6 and 10 mM
      glucose, were not lower than those of controls. ATP concentrations in islets from
      previously malnourished rats fed sucrose at 2 and 10 mM glucose were similar to
      those of controls. Glucose-stimulated insulin release was impaired (by 49-55%) in
      islets from these animals as was the response to keto-isocaproate (by 70%) and
      tolbutamide (by 70%). Under conditions in which ATP-sensitive K+ channels were
      clamped open (40 mM K+ and diazoxide), glucose-stimulated insulin release in
      islets from previously malnourished rats fed sucrose was reduced. These findings
      show that defects in insulin secretion in islets isolated from previously
      malnourished animals are located in both ATP-sensitive K+ channel dependent and
      independent pathways. They do not involve alterations in the early steps of
      glucose handling in the beta-cell, including glucose metabolism and ATP
      generation.

PMID- 9783902
TI  - 1,25-Dihydroxyvitamin D3 enhances degranulation of mast cells.
AB  - The mast cell lines rat basophilic leukemia (RBL) and mouse C57 cells respond to
      IgE/antigen complexes by degranulation. Treatment of these cells with 1,25
      dihydroxyvitamin D3 (1,25(OH)2D3), (10-100 nM) for 24-48 h enhanced IgE/antigen
      induced exocytosis as monitored by release of hexosaminidase. A short term
      incubation with the hormone did not affect exocytosis, ruling out a rapid non
      genomic mechanism. The presence of vitamin D receptors, demonstrated by
      immunoblotting and the lack of effect of 24,25(OH)2D3 suggest a role for these
      receptors in the enhancing effect. 1,25(OH)2D3 also enhanced exocytosis induced
      by the calcium ionophore A23187 in the presence or absence of phorbol ester
      indicating modulation of events distal to signal transduction. 1,25(OH)2D3
      enhanced exocytosis in the presence of cytochalasin D, indicating that the action
      of the hormone is not due to effects on microfilament structure. The results of
      this study suggest that 1,25(OH)2D3 may affect the allergic or pro-inflammatory
      potential of mast cells.

PMID- 9783903
TI  - Action of 1,25(OH)2D3 on the cell cycle genes, cyclin D1, p21 and p27 in MCF-7
      cells.
AB  - 1,25(OH)2D3 is a known growth inhibitor and differentiation inducer of several
      cancer cell lines. To establish the molecular mechanism of 1,25(OH)2D3 as an
      antiproliferating agent, its effect on proliferation and gene regulation was
      studied in human breast cancer MCF-7 cells. 1,25(OH)2D3 inhibited cell
      proliferation dose dependently through G1 arrest. Cyclin D1 transcription levels
      decreased rapidly in 1,25(OH)2D3-treated cells while protein levels only
      decreased after 72 h of treatment. Transcription levels of p21 and p27 were
      upregulated with chronologically consistent changes in cell cycle distribution.
      Experiments with TGF-beta neutralising antibodies revealed that the largest
      effect of 1,25(OH)2D3 on cell proliferation is likely due to a TGF-beta
      independent mechanism of action. The cell cycle regulatory genes, cyclin D1 and
      p27, are probably involved herein as their expression was not affected by the
      presence of neutralising antibodies. However, upregulation of p21 was completely
      abrogated. Therefore, the TGF-beta signalling pathway is thought to be
      responsible for p21 upregulation.

PMID- 9783904
TI  - Placental iodothyronine deiodinase III and II ratios, mRNA expression compared to
      enzyme activity.
AB  - Iodothyronine deiodinases III and II (D3 and D2) specific enzyme activities in
      human placenta both decrease with gestational age. The relation of the enzyme
      activities with their respective mRNA expression was investigated by semi
      quantitative RT-PCR on human placenta mRNA. To investigate if RT-PCR is a useful
      tool to detect iodothyronine deiodinase mRNA, several tissues were screened using
      this technique. In all tissues with iodothyronine deiodinase enzyme activity, the
      corresponding RT-PCR product is present. Similar to D3 specific enzyme activity,
      the amount of D3 mRNA in placenta declines with gestational age. The ratios of
      the D3/D2 enzyme activity and mRNA expression in placenta do not correlate. D3
      enzyme activity shows an average 300-fold excess compared to D2 activity.
      However, semi-quantitative PCR analysis of D3 and D2 mRNA shows a D3/D2 ratio
      varying from 0.05 to 52. These results suggest that the placental D2 mRNA
      amplified is not translated into placental D2 enzyme activity.

PMID- 9783905
TI  - Beta2 adrenergic receptors mediate cAMP, tissue-type plasminogen activator and
      transferrin production in rat Sertoli cells.
AB  - FSH is the main regulator of Sertoli cell function. Nevertheless, several other
      effectors such as catecholamines can also stimulate these cells through the
      adenylyl cyclase transduction pathway. However, the expression of beta adrenergic
      receptors in Sertoli cells is a subject of controversy. The aim of the present
      study was to determine if there are physiologically functional beta adrenergic
      receptors in Sertoli cells and to which subtype(s) they belong. In freshly
      isolated Sertoli cells, isoproterenol, a non selective beta-adrenergic agonist,
      was found to stimulate cAMP production and tissue-type plasminogen activator
      secretion. Specific transcripts for the beta1 and beta2, but not beta3, subtypes
      were detected by RT-PCR analysis. Beta2 transcripts were the form expressed
      predominantly in Sertoli cells. Binding experiments carried out on freshly
      isolated and on cytospined Sertoli cells indicated that in both conditions,
      [125I]iodocyanopindolol binding was inhibited by a non-selective and a 2
      selective antagonist, whereas a beta1 selective antagonist had no effect.
      Scatchard analysis of beta2 specific inhibition revealed a dissociation constant
      of 0.3 nM and a receptor density of 14000 sites per cell. In freshly isolated
      Sertoli cells, we observed that cAMP and tissue-type plasminogen activator were
      stimulated by isoproterenol and a beta2 selective agonist, but not by beta1 or
      beta3 selective agonists. Accordingly, the isoproterenol-stimulated tissue-type
      plasminogen activator responses were abolished by the beta2 selective antagonist
      only. In cultured Sertoli cells, the trend was the same: tissue-type plasminogen
      activator and transferrin secretions were increased by isoproterenol and beta2
      but not by beta1 or beta3 selective agonists. We conclude that freshly isolated
      Sertoli cells express beta2 adrenergic receptors which are functionally coupled
      to adenylyl cyclase and that these characteristics are preserved in cell culture.
      For the tested parameters, catecholamines and FSH effects were similar, but
      response magnitudes were systematically lower with beta agonists than with FSH.
      As norepinephrine is normally present in physiologically-relevant amounts in the
      interstitial fluid, it can be suspected to play a role in the regulation of
      Sertoli cell function.

PMID- 9783907
TI  - GnRH signalling pathways and GnRH-induced homologous desensitization in a
      gonadotrope cell line (alphaT3-1).
AB  - Exposure of the gonadotrope cells to gonadotropin-releasing hormone (GnRH)
      reduces their responsiveness to a new GnRH stimulation (homologous
      desensitization). The time frame as well as the mechanisms underlying this
      phenomenon are yet unclear. We studied in a gonadotrope cell line (alphaT3-1) the
      effects of short as well as long term GnRH pretreatments on the GnRH-induced
      phospholipases-C (PLC), -A2 (PLA2) and -D (PLD) activities, by measuring the
      production of IP3, total inositol phosphates (IPs), arachidonic acid (AA) and
      phosphatidylethanol (PEt) respectively. We demonstrated that although rapid
      desensitization of GnRH-induced IP3 formation did not occur in these cells,
      persistent stimulation of cells with GnRH or its analogue resulted in a time
      dependent attenuation of GnRH-elicited IPs formation. GnRH-induced IPs
      desensitization was potentiated after direct activation of PKC by the phorbol
      ester TPA, suggesting the involvement of distinct mechanisms in the uncoupling
      exerted by either GnRH or TPA on GnRH-stimulated PI hydrolysis. The levels of
      individual phosphoinositides remained unchanged under any desensitization
      condition applied. Interestingly, while the GnRH-induced PLA2 activity was
      rapidly desensitized (2.5 min) after GnRH pretreatments, the neuropeptide-evoked
      PLD activation was affected at later times, indicating an important time
      dependent contribution of these enzymatic activities in the sequential events
      underlying the GnRH-induced homologous desensitization processes in the
      gonadotropes. Under GnRH desensitization conditions, TPA was still able to induce
      PLD activation and to further potentiate the GnRH-evoked PLD activity. AlphaT3-1
      cells possess several PKC isoforms which, except PKCzeta, were differentially
      down-regulated by TPA (PKCalpha, betaII, delta, epsilon, eta) or GnRH (PKCbetaII,
      delta, epsilon, eta). In spite of the presence of PKC inhibitors or down
      regulation of PKC isoforms by TPA, the desensitizing effect of the neuropeptide
      on GnRH-induced IPs, AA and PEt formation remained unchanged. In conclusion, in
      alphaT3-1 cells the GnRH-induced homologous desensitization affects the GnRH
      coupling with PLC, PLA2 and PLD by mechanism(s) which do not implicate TPA
      sensitive PKC isoforms, but likely reflect time-dependent modification(s) on the
      activation processes of the enzymes.

PMID- 9783906
TI  - Heterotrimeric G-protein candidates for Ge in the ACTH secretory pathway.
AB  - The mouse AtT-20/D16-16 anterior pituitary tumour cell line was used to identify
      candidate heterotrimeric G-proteins for G-exocytosis (Ge) which mediates calcium
      ion-stimulated adrenocorticotrophin (ACTH) secretion in this cell line. AtT-20
      cells express several heterotrimeric G-protein alpha subunits; Gs alpha, Gt
      alpha, Gq alpha, G11alpha, G12alpha, G13alpha, G14alpha, G15alpha, Gz alpha,
      Gi2alpha, Gi3alpha, and Go alpha and so heterotrimeric G-protein selective agents
      were used to differentiate between these candidates. Agents which stimulate ACTH
      secretion via Ge were not pertussis toxin (PTX)-sensitive nor was cholera toxin
      (CTX) able to stimulate ACTH secretion from permeabilised cells in the absence of
      calcium. G-protein antagonists which inhibit activation of Gs, Gi, and Gq
      subfamilies did not attenuate Ge-stimulated ACTH secretion from permeabilised AtT
      20 cells. In AtT-20 cells the stimulatory G-protein involved in the late stages
      of the ACTH secretory pathway does not belong to the Gs, Gi (with the exception
      of Gz) or Gq subfamilies of heterotrimeric G-proteins leaving Gz, G12 or G13 as
      the strongest candidates for Ge.

PMID- 9783908
TI  - The molecular characterisation of chicken pituitary N-terminal pro
      opiomelanocortin (POMC).
AB  - Monoclonal antibodies (Mabs) specifically recognizing the chicken pituitary
      corticotropes were used to isolate a population of closely related peptides from
      crude chicken pituitary extracts. A homogeneous N-terminal sequence homologous to
      the extreme N-terminus of mammalian and amphibian pro-opiomelanocortin (POMC) was
      revealed. Further physicochemical analysis proved the existence of a series of C
      terminally truncated peptides including 3 major molecular species corresponding
      to Ser1-Gly64, Ser1-Arg73 and Ser1-Gly105 respectively. The two latter molecules
      were shown to be N-glycosylated at position Asn67, with mass spectrometric data
      indicating a carbohydrate structure of the oligomannose 5 type, in addition to
      two more complex structures. No evidence was found in favour of O-glycosylation
      on Ser47. Degenerated PCR primers were deduced from the above protein sequence
      and from the known chicken adrenocorticotropic hormone (ACTH) sequence. The
      nucleotide sequence obtained by reversed transcription PCR (RT-PCR) completely
      confirmed the new amino acid sequence data including pro-gamma-MSH, the joining
      peptide and ACTH.

PMID- 9783910
TI  - Functional interactions of an upstream enhancer of the mouse glycoprotein hormone
      alpha-subunit gene with proximal promoter sequences.
AB  - Transcription of the glycoprotein hormone alpha-subunit gene in the pituitary is
      governed by different promoter elements in thyrotropes and gonadotropes. We
      recently identified an upstream enhancer that directs a high level of cell type
      specific expression in transgenic mice and stimulates proximal promoter activity
      in cultured alphaTSH and alphaT3 cells. To assess the contribution of promoter
      sequences that functionally interact with the enhancer, we mutated two proximal
      elements shown to be important in both thyrotrope and gonadotrope cells.
      Disruption of the pituitary glycoprotein hormone basal element (PGBE), which
      binds a LIM homeodomain protein, resulted in a decrease in basal promoter
      activity in both alphaTSH and alphaT3 cells. Enhancer function was completely
      abolished by the PGBE site mutation in alphaT3 gonadotropes, whereas some
      stimulatory activity remained in alphaTSH thyrotropes. Mutation of the
      gonadotrope specific element (GSE), which binds SF1 and is important for basal
      activity in gonadotropes and TRH response in thyrotropes, resulted in declines in
      basal and enhanced promoter activity only in alphaT3 cells and not in alphaTSH
      cells. Despite this decrease in enhanced activity, the GSE mutated promoter still
      retained some enhancer stimulated activity, suggesting that the PGBE site still
      functionally interacts in the absence of an intact GSE. This mutation had no
      effect in alphaTSH cells. These data suggest that although the enhancer works in
      both cell types it exhibits cell type specific functional characteristics.

PMID- 9783909
TI  - Differential RNA display identifies novel genes associated with decreased vitamin
      D receptor expression.
AB  - To characterize further the function of the intracellular vitamin D receptor
      (VDR), we have developed stable transfectant variants of a vitamin D-responsive
      cell line (U937) which express either decreased or increased numbers of VDR. In
      this study we have analyzed changes in gene expression associated with this
      variable VDR expression. Initial experiments indicated that a 50% decrease in VDR
      levels was associated with a 2-fold increase in cell proliferation and a similar
      rise in c-myc mRNA expression. Further studies were carried out using
      differential RNA display (DD). Sequence analysis of DD products revealed two
      cDNAs with identity to known gene products: the catalytic sub-unit of DNA-protein
      kinase (DNA-PK(CS)), and the peroxisomal enzyme 17beta-hydroxysteroid
      dehydrogenase type IV (17beta-HSD IV). Northern analysis confirmed that
      expression of both mRNAs was reduced in cells with decreased numbers of VDR. Down
      regulation of 17beta-HSD IV mRNA expression was associated with enhanced
      estradiol inactivation by U937 cells, suggesting a link between estrogenic
      pathways and cell proliferation. Further Northern analyses indicated that there
      was no significant change in 17beta-HSD IV or DNA-PK(CS) mRNA levels following
      treatment with 1,25(OH)2D3, although expression of both genes varied with changes
      in cell proliferation. These data suggest that, in addition to its established
      role as a hormone-dependent trans-activator, VDR may influence gene expression by
      ligand-independent mechanisms.

PMID- 9783911
TI  - Ovarian immune cells express granulocyte-macrophage colony-stimulating factor (GM
      CSF) during follicular growth and luteinization in gonadotropin-primed immature
      rodents.
AB  - To obtain clues as to whether granulocyte-macrophage colony-stimulating factor
      (GM-CSF) is related to ovarian physiology, the sites, the gene expression and the
      production of GM-CSF in the ovary during follicular development and luteinization
      were studied in equine CG (eCG)-primed immature mice and rats. During follicular
      development, the expression of GM-CSF mRNA was localized in theca-interstitial
      tissues, oocytes and granulosa cells of small developing follicles in mice. In
      the mouse ovary after ovulation, luteal tissues as well as the above components
      had intense signals for GM-CSF mRNA. Mast cells, which were present mainly in the
      ovarian medulla, also expressed mRNA for GM-CSF in rats. Immunohistochemical
      analyses with two different antibodies against murine GM-CSF revealed that GM-CSF
      like immunoreactivity was detectable mainly in theca-interstitial, luteal
      tissues, oocytes and mast cells. Intense GM-CSF positive cells in theca
      interstitial and luteal tissues were stained with anti-CD11b antibody in mice.
      Messenger RNAs for GM-CSF receptor subunits were expressed in mast cells of the
      medulla and in luteal tissues in rat ovary. The levels of GM-CSF released into
      the culture media by rat ovarian dispersed cells 1-2 days after eCG treatment
      were higher than those before the treatment, although no significant change in
      the levels of ovarian GM-CSF mRNA was detected by reverse transcription
      polymerase chain reaction analysis. The secretion of GM-CSF was also increased by
      treatment of the cells with immune stimulators such as phorbol ester, interleukin
      1 and lipopolysaccharide. These data indicate that ovarian macrophages and mast
      cells in addition to theca-interstitial cells, synthesize and release GM-CSF
      during ovarian cycles, and that ovarian GM-CSF secreting capacity is enhanced
      during early stages of follicular development in rodents.

PMID- 9783912
TI  - The unique exon 10 of the human luteinizing hormone receptor is necessary for
      expression of the receptor protein at the plasma membrane in the human
      luteinizing hormone receptor, but deleterious when inserted into the human
      follicle-stimulating hormone receptor.
AB  - The LH receptor (LHR) is a member of the family of G protein-coupled seven-times
      plasma membrane transversing receptors. Its gene consists of 11 exons, the last
      one encoding the transmembrane and intracellular domains of the receptor. The
      FSHR, and its gene, resemble structurally those of the LHR, with the exception
      that the sequences corresponding to exon 10 in LHR are missing in FSHR, which is
      thus encoded by a total of ten exons. Our recent studies on the marmoset monkey
      testis LHR cDNA indicated that an 81 bp nucleotide sequence, encoding the
      complete exon 10 of the LHR gene in other mammalian species, is absent in this
      species without affecting the LHR function. To study further the role of the exon
      10 encoded sequences of the LHR in the gonadotropin receptor function, a deletion
      of exon 10 from the human LHR (hLHdeltaexon10R), and a chimeric hFSHR with exon
      10 from hLHR inserted (hFSHLHexon10R), were constructed in expression vectors.
      The results presented here demonstrate that 293 cells transfected with the
      hLHdeltaexon10R display a decrease in the proportion of the receptor binding at
      the cell surface, compared with cells transfected with wild-type hLHR. However,
      the cells expressing hLHdeltaexon10R showed similar high affinity binding of
      [125I]iodo-hCG as those transfected with wild-type hLHR, in either intact cells
      or their detergent extracts. In addition, cells expressing the hLHdeltaexon10R
      and wild-type hLHR displayed similar dose-response of cAMP production to hCG
      stimulation. Cells transfected with chimeric hFSHLHexon10R showed barely
      detectable [125I]iodo-FSH binding in intact cells compared with those transfected
      with wild-type hFSHR. The FSH binding detected in cellular detergent extracts
      displayed 10-fold lower binding activity than wild-type receptors, in spite of
      similar level of immunoreactive FSHR protein expression in the transfected cells.
      The hFSHLHexon10R had a modest 5-fold lower binding affinity for FSH as compared
      with wild-type hFSHR. In conclusion, the present study indicates that the
      sequences encoding exon 10 of the hLHR are essential for the LHR expression at
      the plasma membrane, but deleterious for function if inserted into the hFSHR.

PMID- 9783914
TI  - Role of TNF receptor 1 in protein turnover during cancer cachexia using gene
      knockout mice.
AB  - The implantation of the Lewis lung carcinoma (a fast-growing mouse tumour that
      induces cachexia) to both wild-type and gene-deficient mice for the TNF-alpha
      receptor type I protein (Tnfr1 degree/Tnfr1 degree), resulted in a considerable
      loss of carcass weight in both groups. However, while in the wild-type mice there
      was a loss of both fat and muscle, in the gene-knockout mice muscle wastage was
      not affected to the same extent. In both groups, tumour burden resulted in
      significant increases in circulating TNF-alpha, a cytokine which, as we have
      previously demonstrated, can induce protein breakdown in skeletal muscle. Muscle
      wastage in wild-type mice was accompanied by an increase in the fractional rate
      of protein degradation, while no changes were observed in protein synthesis. The
      result is a decreased rate of protein accumulation that accounts for the muscle
      weight loss observed as a result of tumour burden. In contrast, gene knockout
      mice did not have significantly lower rates of protein accumulation as a result
      of tumour implantation. The increase in protein degradation in the tumour-bearing
      wild mice was accompanied by an enhanced expression of both ubiquitin and
      proteasome subunit genes, all of them related to the activation of the ATP
      dependent proteolytic system in skeletal muscle. Tumour-bearing gene-deficient
      mice did not show any increase in gene expression. It is concluded that TNF-alpha
      (alone or in combination with other cytokines) is responsible for the activation
      of protein breakdown in skeletal muscle of tumour-bearing mice.

PMID- 9783913
TI  - An ACTH-producing small cell lung cancer expresses aberrant glucocorticoid
      receptor transcripts from a normal gene.
AB  - ACTH production by non-pituitary tumors is generally not suppressible by
      exogenous glucocorticoid administration. We had postulated that defects in the
      glucocorticoid receptor (GR) signaling system might be responsible for this
      apparent glucocorticoid resistance and had previously demonstrated that DMS-79
      cells, derived from an ectopic ACTH-producing tumor, express an abnormal GR mRNA.
      In this DMS-79 cell GR the sequence normally derived from exons 8 and 9 is
      replaced by sequence unmatched in the DNA databases. The protein encoded by this
      mRNA lacks the steroid-binding domain and does not function as a ligand-activated
      transcription factor. In the present work, we sought to identify the origin of
      the novel GR mRNA sequence. Southern blot analysis of DMS-79 genomic DNA showed
      no major structural alteration of the GR gene. Southern blotting of cosmid clones
      of the normal GR gene revealed that the novel DMS-79 GR mRNA sequence is derived
      from intron G, between exons 7 and 8. No splice site mutations were found in PCR
      amplified DMS-79 DNA fragments surrounding the downstream splice junctions.
      Further sequencing indicated that the aberrant GR transcript appears to be
      generated by use of a consensus cleavage/polyadenylation signal found 3650 base
      pairs into the normal intron G. We conclude that abnormal GR pre-mRNA processing
      rather than a GR gene mutation confers glucocorticoid resistance on DMS-79 cells.

PMID- 9783915
TI  - Procorticotrophin-releasing hormone: endoproteolytic processing and differential
      release of its derived peptides within AtT20 cells.
AB  - Procorticotrophin-releasing hormone (proCRH) is expressed mainly in the
      hypothalamus and in the placenta, where it undergoes tissue-specific
      endoproteolysis. Our results show that within stably transfected AtT20/D16V cells
      proCRH is cleaved to generate two fragments of approximately 8 and 3 kDa which
      could account for proCRH(125-194) and proCRH(125-151), respectively, and a 4.5
      kDa product which could account for mature IR-CRH(1-41). The immunofluorescence
      staining patterns for IR-CRH and IR-ACTH and their response of secretagogues
      indicate targeting of proCRH and POMC to the secretory pathway in transfected
      AtT20 cells. In this work, we have used a unique set of specific RIAs and IRMAs
      to the full length POMC and proCRH molecules and several products of
      endoproteolytic processing to assess if they could be released differentially in
      response to stimulation. Although the release of both IR-ACTH and IR-CRH peptides
      from transfected AtT20 cells is stimulated in response to exposure to high
      potassium stimulation (51 mM KCl/SmM CaCl2), the sorting index (SI) suggests that
      mature ACTH is sorted to the regulated secretory pathway 2.1-fold more
      efficiently than mature CRH(1-41). Mature ACTH is also sorted to the regulated
      secretory pathway 9-fold more efficiently than IR-proCRH(125-151). Also, mature
      CRH(1-41) is sorted to the regulated secretory pathway 3-fold more efficiently
      than IR-proCRH(125-151). These results therefore indicate that the intracellular
      mechanisms for the storage and release of POMC, proCRH and their endoproteolytic
      products differ and would sustain the hypothesis that within mammalian
      peptidergic cells, different biologically active peptides originating from the
      same or different precursor molecules, could be differentially released in
      response to specific stimuli. This would give these cells the capacity to finely
      regulate neurotransmitter release in response to environmental and physiological
      demands.

PMID- 9783916
TI  - Bisphenol A interacts with the estrogen receptor alpha in a distinct manner from
      estradiol.
AB  - We investigated the interaction of bisphenol A (BPA, an estrogenic environmental
      contaminant used in the manufacture of plastics) with the estrogen receptor alpha
      (ERalpha) transfected into the human HepG2 hepatoma cell line and expanded the
      study in vivo to examine the effect of BPA on the immature rat uterus. Bisphenol
      A was 26-fold less potent in activating ER-WT and was a partial agonist with the
      ERalpha compared to E2. The use of ERalpha mutants in which the AF1 or AF2
      regions were inactivated has permitted the classification of ER ligands into
      mechanistically distinct groups. The pattern of activity of BPA with the ERalpha
      mutants differed from the activity observed with weak estrogens (estrone and
      estriol), partial ERalpha agonists (raloxifene or 4-OH-tamoxifen), or a pure
      antagonist (ICI 182, 780). Intact immature female Sprague-Dawley rats were
      exposed to BPA alone or with E2 for 3 days. Unlike E2, BPA had no effect on
      uterine weight; however, like E2, both peroxidase activity and PR levels were
      elevated, though not to the level induced by E2. Following simultaneous
      administration, BPA antagonized the E2 stimulatory effects on both peroxidase
      activity and PR levels but did not inhibit E2-induced increases of uterine
      weight. These results demonstrate that BPA is not merely a weak estrogen mimic
      but exhibits a distinct mechanism of action at the ERalpha.

PMID- 9783917
TI  - Electrically stimulated myoplasty for functional sphincter reconstruction.

PMID- 9783918
TI  - Glyoxylate synthesis, and its modulation and influence on oxalate synthesis.
AB  - PURPOSE: We define the major pathways of hepatic oxalate synthesis in humans,
      examine the association with other metabolic pathways and identify ways that
      oxalate synthesis may be modified. In addition, we suggest what is required for
      further progress in this area. MATERIALS AND METHODS: We consolidated relevant
      data primarily from recently published literature, considered new pharmacological
      approaches to decrease oxalate synthesis, and formulated an overview of the
      regulation and modification of oxalate synthesis pathways. RESULTS: Experiments
      with animals, including humans, animal cells and in vitro preparations of
      cellular components, support the existence of a major metabolic pathway linking
      the amino acids serine, glycine and alanine. Oxalate synthesis is a minor,
      secondary reaction of a cascade of reactions termed the glyoxylate pathway, which
      has a prominent role in gluconeogenesis and ureagenesis. The enzymatic steps and
      effectors which regulate glyoxylate and oxalate synthesis are not well
      characterized. Pharmacological approaches can reduce oxalate synthesis by
      diminishing the glyoxylate pool and possibly modifying enzymatic reactions
      leading to glyoxylate synthesis. CONCLUSIONS: The individual steps associated
      with glyoxylate and oxalate synthesis can be identified. The glyoxylate pathway
      has a significant functional role in intermediary liver metabolism but the way it
      is regulated is uncertain. Oxalate synthesis can be modified by drugs, indicating
      that primary and idiopathic hyperoxaluria may respond to pharmacological
      intervention.

PMID- 9783919
TI  - Testicular calcifications: incidence, histology and proposed pathological
      criteria for testicular microlithiasis.
AB  - PURPOSE: Testicular microlithiasis is a clinical syndrome in which men present
      with innumerable testicular calcifications. Indirect evidence suggests that this
      syndrome may be associated with an increased risk of germ cell neoplasia. The
      incidence and types of testicular calcification in normal and diseased testes is
      unknown. MATERIALS AND METHODS: A series of 131 orchiectomy specimens were
      reviewed, including 79 germ cell tumors, and 100 entirely embedded autopsy testes
      in men with no known testicular pathology. RESULTS: Two types of calcifications
      were identified. Hematoxylin bodies, consisting of amorphous calcific debris,
      were present in 6 cases associated with germ cell tumors. In contrast, laminated
      calcifications were found not only in association with germ cell tumors (35
      cases), but also in 2 of 4 cryptorchid testes and 6 of the remaining 145 testes
      (4%). Of these calcifications 61% were multiple. When laminated calcifications
      were associated with germ cell tumors there was an increased incidence of
      extension beyond the tunica albuginea (43 versus 21%) and lymphatic invasion (52
      versus 17%, p = 0.046 and 0.012, respectively). CONCLUSIONS: Testicular
      calcifications are heterogeneous. Hematoxylin bodies are specific for germ cell
      tumors but laminated calcifications, while more common in germ cell tumors, also
      occur in otherwise normal testes. The pathological criteria for testicular
      microlithiasis should include the identification of multiple laminated
      calcifications within seminiferous tubules.

PMID- 9783920
TI  - Medical reduction of stone risk in a network of treatment centers compared to a
      research clinic.
AB  - PURPOSE: We determined whether a network of 7 comprehensive kidney stone
      treatment centers supported by specialized stone management software and
      laboratory resources could achieve reductions in urine supersaturation comparable
      to those in a single research clinic devoted to metabolic stone prevention.
      MATERIALS AND METHODS: Supersaturation values for calcium oxalate, calcium
      phosphate and uric acid in 24-hour urine samples were calculated from a set of
      kidney stone risk factor measurements made at a central laboratory site for the
      network and research laboratory for the clinic. Individual results and group
      outcomes were presented to each center in time sequential table graphics. The
      decrease in supersaturation with treatment was compared in the network and clinic
      using analysis of variance. RESULTS: Supersaturation was effectively reduced in
      the network and clinic, and the reduction was proportional to the initial
      supersaturation value and increase in urine volume. The clinic achieved a greater
      supersaturation reduction, higher fraction of patient followup and greater
      increase in urine volume but the treatment effects in the network were,
      nevertheless, substantial and significant. CONCLUSIONS: Given proper software and
      laboratory support, a network of treatment centers can rival but not quite match
      results in a dedicated metabolic stone research and prevention clinic. Therefore,
      large scale stone prevention in a network system appears feasible and effective.

PMID- 9783921
TI  - Long-term outcome of caliceal diverticula following percutaneous endosurgical
      management.
AB  - PURPOSE: We review the morbidity and long-term outcome of percutaneous caliceal
      diverticulectomy and associated stone extraction. MATERIALS AND METHODS:
      Percutaneous caliceal diverticulectomy was performed in 19 women and 11 men (age
      range 20 to 58 years), of whom 26 had stones (all 15 mm. or less). The
      diverticula were located throughout the kidney, including the upper (11
      patients), middle (15) and lower (4) calices. Percutaneous caliceal
      diverticulectomy included 28 direct and 2 indirect accesses (1 via a previously
      placed nephrostomy tract and 1 due to stones in other areas of the kidney). In
      all cases the stone was removed and the diverticular neck was incised or dilated.
      Fulguration of the diverticular walls was performed in 22 cases.
      Transdiverticular percutaneous renal and ureteral drainage was maintained from 2
      to 7 days until a nephrostogram demonstrated no extravasation. RESULTS: The
      average operating room time and hospital stay were 171 minutes (range 75 to 330)
      and 4.1 days (range 2 to 7), respectively. Major complications occurred in 6.6%
      of the cases, requiring 1 blood transfusion and 1 chest tube placement, and minor
      complications occurred in 13.4%. There was no mortality. Followup for more than 1
      year was available in 27 patients. Stone-free rate was 93% with obliteration of
      the diverticulum in 76% of patients. Overall, 85% of patients are asymptomatic at
      average followup of 3.5 years (range 1 to 7.3). CONCLUSIONS: Direct percutaneous
      endosurgical management provides a safe, efficacious and durable means of
      treating stone bearing caliceal diverticula, regardless of stone size or location
      of the diverticulum.

PMID- 9783922
TI  - Metabolic abnormalities in patients with caliceal diverticular calculi.
AB  - PURPOSE: We determined the incidence and spectrum of metabolic abnormalities in
      patients with caliceal diverticular calculi. MATERIALS AND METHODS: Five men and
      9 women with caliceal diverticular calculi underwent metabolic evaluation,
      including determination of serum electrolytes, calcium, phosphate and uric acid,
      and 24-hour urinary volume, creatinine, calcium, oxalate, uric acid and citrate.
      RESULTS: Of the 14 patients 7 (50%) had urinary excretion abnormalities promoting
      stone formation, including hypercalciuria in 3, hyperoxaluria in 1,
      hypercalciuria combined with hyperuricosuria in 1 and hyperoxaluria combined with
      hyperuricosuria in 2. Two patients had a history of gout while another had
      radiographic evidence of medullary sponge kidney. Of the patients 9 (64.3%) had a
      history of synchronous or metachronous calculi distant from the involved caliceal
      diverticular stone and 5 (55.6%) of these 9 had definable metabolic disorders.
      However, there was no statistically significant difference in urinary excretion
      values between patients with or without a history of additional extra
      diverticular stones. CONCLUSIONS: Urinary stasis alone does not explain stone
      formation in a significant number of patients with caliceal diverticular calculi.
      Rather, the local physiological environment of the urine likely has a
      predisposing role and evaluation for metabolic abnormalities should be
      considered. In some patients cure may be effected by treating the stone and any
      associated metabolic disorders rather than the diverticulum.

PMID- 9783923
TI  - Ureteroscopic treatment of ureteropelvic junction obstruction.
AB  - PURPOSE: Endopyelotomy has increasingly become well accepted as the optimal
      management for primary and secondary ureteropelvic junction obstruction. We
      report our experience with ureteroscopic endopyelotomy guided by endoluminal
      ultrasound. MATERIALS AND METHODS: Ureteroscopic endopyelotomy was attempted in
      27 patients with primary and 10 with secondary ureteropelvic junction
      obstruction. Retrograde pyelogram and endoluminal ultrasound were performed at
      the start of the procedure in all patients. Based on sonographic findings 5
      patients were not considered candidates for the procedure. The remaining 13 men
      and 19 women were treated ureteroscopically with a rigid ureteroscope in 5
      (15.6%), flexible in 20 (62.5%), and rigid and flexible in 7 (21.9%) patients.
      Stents were placed postoperatively for 6 to 10 weeks. The patients were followed
      for a mean duration of 10 months. RESULTS: The procedure was completed in all
      patients. Average operating time was 95 minutes including the time for imaging.
      Sonographic localization guided the site of incision in all patients and changed
      therapy in 5. It identified crossing vessels in 10 patients (31%), septum
      denoting high insertion in 5 (15.5%) and both in 7 (22%). Preoperative stenting
      was not required in any patient. Morbidity was low with no patients requiring
      transfusion and no evidence of ureteral strictures. Success, defined as pain-free
      with resolution of obstruction on diuretic renal scan, was achieved in 28 of the
      32 patients (87.5%). CONCLUSIONS: Ureteroscopic endopyelotomy is a safe and
      effective treatment for most cases of ureteropelvic junction obstruction.
      Endoluminal ultrasonography of the obstructed ureteropelvic junction has gained a
      major role in defining which patient to treat and in directing endoluminal
      incisions to minimize the risk of injury to adjacent vessels. There is a higher
      failure rate when vessels are present.

PMID- 9783924
TI  - Small diameter, actively deflectable, flexible ureteropyeloscopy.
AB  - PURPOSE: We studied and developed ureteroscopic technique and instrumentation
      beyond our initial experience with small diameter, actively deflectable, flexible
      ureteropyeloscopy. MATERIALS AND METHODS: Flexible ureteropyeloscopy was
      performed at 2 university centers in 492 consecutive patients. Endoscope designs
      and development were based on strict specifications, including 8F or less tip
      diameter, 3.6F or greater working channel, 2-way active tip deflection and
      secondary deflection for lower pole intrarenal access. Flexible ureteroscopes
      manufactured by 5 companies were studied through various prototypic steps and
      surgical technique. Complementary accessories were developed for specific
      treatments, including endoscopic lithotripsy, management of urothelial lesions,
      treatment of upper urinary tract obstruction (that is strictures) and
      percutaneous access with ureteroscopic assistance in select complex cases.
      RESULTS: A total of 584 procedures were performed with the small diameter,
      actively deflectable, flexible ureteroscopes. Flexible ureteropyeloscopic access
      was always preformed over a working guide wire without an operative sheath. In
      addition, the 10F dual lumen catheter was the primary device used to obtain 2
      guide wires (working and safety), and gently and minimally dilate the intramural
      segment. Larger dilators were required in only 12% of procedures. The entire
      intrarenal collecting system was accessed in 94% of cases with lower pole access
      requiring secondary or passive deflection in 60% of procedures. Endoscopic
      lithotripsy was the most common procedure performed in this series (303, 52%).
      Small diameter, flexible ureteroscopy and holmium laser lithotripsy were
      successful in 97% of patients with ureteral and 79% with intrarenal calculi. When
      a 2-stage ureteropyeloscopy procedure was used for large upper urinary tract
      calculi, the success rate for intrarenal calculi increased to 91%. Endoscopic
      biopsy and treatment of upper urinary tract transitional cell carcinoma were
      performed in 101 procedures (17%), while retrograde ureteroscopic incision for
      stricture disease was performed in 36 (6%). The overall major complication rate
      was less than 1% and there were no ureteral perforations, avulsions, sepsis or
      deaths. These new endoscopes were more fragile than larger predecessors but a
      maximum of 30 procedures were performed between interval repair. CONCLUSIONS:
      Small diameter, actively deflectable, flexible ureteropyeloscopy facilitates
      various minimally invasive endoscopic therapies. Although this class of endoscope
      has greater fragility, it is easy to use and has broadened the therapeutic range
      of ureteroscopic treatment to include intrarenal lesions.

PMID- 9783925
TI  - Xylose absorption and metabolic status in urinary intestinal orthotopic
      reservoir: ileocecal compared with ileal neobladder.
AB  - PURPOSE: We compare the absorption of D-xylose and vitamin B12, and the metabolic
      status in ileocecal and ileal orthotopic neobladders. MATERIALS AND METHODS: D
      xylose plasma levels after an oral load, body composition, plasma vitamin B12,
      acid base and electrolyte balance were studied in 33 patients with an ileocecal
      reservoir and 13 patients with an ileal reservoir. Mean followup was 55 months.
      Results of both types of operation and a healthy control group were compared.
      RESULTS: Plasmic levels of D-xylose and vitamin B12 were significantly lower in
      the ileal reservoir than in ileocecal reservoir group and normal controls.
      CONCLUSIONS: Despite an acceptable body composition, intestinal malabsorption
      could be present in patients with an ileal reservoir but the ileocecal tract
      appears to be safe.

PMID- 9783926
TI  - Decreased elastin gene expression in noncompliant human bladder tissue: a
      competitive reverse transcriptase-polymerase chain reaction analysis.
AB  - PURPOSE: In low capacity noncompliant fibrotic bladders, as seen in patients with
      myelomeningocele, elevated storage pressures ultimately can lead to renal damage.
      Earlier studies have described an increased deposition of extracellular matrix
      protein, especially type III collagen, in the detrusor muscle. We analyzed
      elastin gene expression and quantified elastin gene alteration in the obstructed
      bladder, correlating urodynamically measured compliance with elastin messenger
      ribonucleic acid (mRNA) concentration. MATERIALS AND METHODS: Using a reverse
      transcriptase-polymerase chain reaction quantitative technique elastin mRNA can
      be reliably measured in 5 to 8 mg. samples of bladder tissue. We compared tissue
      samples from patients with urodynamically demonstrated noncompliant bladders
      (less than 10 cc/cm. water) to a control group with normal bladder compliance
      (greater than 20 cc/cm. water). Tissue samples were homogenized and sonicated,
      and complementary deoxyribonucleic acid (cDNA) was synthetized from mRNA using
      reverse transcriptase. Wild type and mutant elastin cDNA were synthetized, and
      target elastin cDNA with unknown concentration was competitively co-amplified
      with known serial dilutions of the mutant template (competitive polymerase chain
      reaction). Computerized densitometry allowing cDNA concentration measurement was
      performed and competitive reverse transcriptase-polymerase chain reaction was
      repeated at least twice for every sample. RESULTS: Elastin mRNA concentration
      ranged from 27.6 to 63.2 attomole per mg. in noncompliant bladders compared to 62
      to 190 attomole per mg. in controls. The variation within the same sample was
      less than 10%. There was a statistically significant difference between mean plus
      or minus standard deviation elastin cDNA concentration in noncompliant bladders
      (37.48 attomole per mg. +/- 12.06) and controls (119.63+/-41.01 attomole per
      mg.). CONCLUSIONS: A significant decrease in elastin mRNA matches the decreased
      deposition of elastic fibers noted in previous immunohistochemical studies. Our
      data suggest that this decrease is mainly due to a transcriptional down
      regulation of the elastin gene in noncompliant bladders.

PMID- 9783927
TI  - Cystoscopic findings consistent with interstitial cystitis in normal women
      undergoing tubal ligation.
AB  - PURPOSE: We test the hypothesis that women without chronic pelvic pain or
      irritative voiding symptoms do not demonstrate petechial hemorrhages known as
      glomerulations that are characteristic of patients with interstitial cystitis.
      MATERIALS AND METHODS: A prospective cohort design was used for examination with
      cystoscopy and bladder distention of 20 asymptomatic women undergoing tubal
      ligation. Cystoscopy with the patient under general anesthesia was performed to
      inspect the bladder mucosa before and after distention at 70 cm. of water
      pressure for 2 or 6 minutes. Photographs of the right, posterior and left of the
      bladder surfaces taken before and after the distention were scored on a scale of
      1 to 5 using a panel of standards. Five urologists blinded to the source of
      individual photographs independently evaluated 120 research images interspersed
      with 46 other pictures from a library containing images from 19 symptomatic
      patients with and without interstitial cystitis. RESULTS: A total of 20 normal
      women with a mean age plus or minus standard deviation of 29+/-6 years consented
      to participate in this trial during laparoscopic tubal ligation. Photographs of
      bladder sites before and after distention with 890+/-140 ml. were scored as 1.4+/
      0.3 (before distention) and 3.1+/-1.1 (after distention) on the scale of 1 to 5.
      The increase in scores following distention in normal subjects was seen to the
      same degree and in the same proportion as in patients with symptoms of
      interstitial cystitis (8 of 19 symptomatic patients in this series met current
      diagnostic criteria for interstitial cystitis). Slight but significant
      differences were seen among sites in the bladder but not between 2 and 6-minute
      distention durations. CONCLUSIONS: Bladder mucosal lesions characteristically
      associated with irritative voiding symptoms and pelvic pain in patients diagnosed
      with interstitial cystitis were observed in asymptomatic women.

PMID- 9783928
TI  - Results of a randomized phase III trial of sequential intravesical therapy with
      mitomycin C and bacillus Calmette-Guerin versus mitomycin C alone in patients
      with superficial bladder cancer.
AB  - PURPOSE: We study toxicity and efficacy of sequential intravesical therapy with
      mitomycin C and bacillus Calmette-Guerin (BCG) in patients with intermediate or
      high risk superficial bladder cancer compared to the use of intravesical
      mitomycin C alone. MATERIALS AND METHODS: Patients with intermediate and high
      risk papillary superficial bladder cancer and carcinoma in situ were randomized
      after transurethral resection between 4 weekly instillations with 40 mg.
      mitomycin C followed by 6 weekly instillations with BCG (group 1, 90 patients) or
      10 weekly instillations with mitomycin C (group 2, 92 patients). RESULTS: The
      frequency of bacterial and chemical cystitis, and other local side effects was
      similar in both groups. Allergic reactions, including skin rash, were more
      frequent in the mitomycin C only group (12 of 92 patients versus 5 of 90, p =
      0.08), and other systemic side effects were more frequent in the sequential group
      (16 of 90 versus 8 of 92, p = 0.07). After a median followup of 32 months the
      number of recurrences (sequential 35 of 90 patients versus mitomycin C only 42 of
      92, p = 0.36) and progression (5 of 90 versus 4 of 92 respectively, p = 0.70)
      were similar in both groups. CONCLUSIONS: We did not find any major differences
      in toxicity or treatment efficacy with intravesical mitomycin C and the
      sequential use of BCG or mitomycin C for intermediate and high risk superficial
      papillary bladder cancer.

PMID- 9783929
TI  - A phase I/II trial of transurethral surgery combined with concurrent cisplatin, 5
      fluorouracil and twice daily radiation followed by selective bladder preservation
      in operable patients with muscle invading bladder cancer.
AB  - PURPOSE: We describe a protocol designed to evaluate the use of twice daily
      radiation used together with cisplatin and 5 fluorouracil (5-FU) in the treatment
      of operable transitional cell carcinoma of the bladder with potential bladder
      preservation. MATERIALS AND METHODS: A total of 18 consecutive patients with T2
      T4a bladder tumors underwent as complete a transurethral resection as possible,
      which was visibly complete in 14 cases. They then received twice daily radiation
      and infusion cisplatin and 5-FU during an induction phase. No therapy was given
      for 3 weeks, following which patients were reevaluated cystoscopically. Cases of
      clinical complete response by biopsy and cytology were consolidated with further
      chemotherapy/radiation using the same chemotherapeutic agents and radiation
      schedule. Patients who had incomplete responses were advised to undergo an
      immediate radical cystectomy. Of the 18 patients 15 subsequently received 3
      cycles of adjuvant chemotherapy, consisting of methotrexate, cisplatin and
      vinblastine. Median followup for the entire group is 32 months. RESULTS: Of the
      18 patients 14 had no detectable tumor after induction therapy. Of the 4 patients
      with persistent tumor 2 underwent radical cystectomy and 2 refused cystectomy, 1
      of whom was treated with partial cystectomy and the other with consolidation
      chemotherapy/radiation. The actuarial overall survival at 3 years was 83%. The
      chance of a patient being alive at 3 years with a native bladder was 78%. No
      patient required cystectomy for hematuria or bladder shrinkage. Three patients in
      whom superficial tumors developed were treated successfully with bacillus
      Calmette-Guerin. Small bowel obstruction in 1 case was corrected surgically.
      CONCLUSIONS: This pilot study demonstrates a high rate of response to this
      combined chemotherapy/radiation regimen in conjunction with a visibly complete
      transurethral resection. Reevaluation after a short induction phase allows for
      the early selection of patients with persistent disease for radical cystectomy.

PMID- 9783930
TI  - Bladder preservation in patients with bladder cancer--quality versus quantity of
      life?

PMID- 9783931
TI  - Long-term followup and selection criteria for penile revascularization in
      erectile failure.
AB  - PURPOSE: We report the long-term results of penile revascularization surgery for
      erectile failure and suggest possible selection criteria for this controversial
      surgical procedure. MATERIALS AND METHODS: In 7 years 62 impotent men who did not
      respond to pharmacotherapy underwent microsurgical penile revascularization and
      completed long-term followup evaluation in 41 months (range 18 to greater than
      62) consisting of a detailed questionnaire, duplex sonography and optional
      pharmacotherapy or angiography. The Virag procedure was chosen for the first 7
      patients, the original Hauri technique for the next 13 and the modified Mannheim
      triple anastomosis for 42. RESULTS: Of all patients 34% achieved spontaneous and
      another 20% pharmacologically induced erections. Success in diabetics and older
      patients was lower (43% for diabetics, 39% for those older than 50 years at
      surgery), while it was high in men with less than 2 risk factors (58%) as well as
      in younger patients (69% for those up to 50 years old). Shunt patency was 92%.
      Complications such as glans hyperemia developed in 13% of patients, shunt
      thrombosis in 8% and inguinal hernias in 6.5%. CONCLUSIONS: Patient selection is
      vital for the successful outcome of penile revascularization surgery. We adhere
      to strict selection criteria, such as patient age maximum of 50 years, less than
      2 risk factors, no recent diabetes and termination of nicotine abuse. Penile
      revascularization surgery is highly indicated in this group of patients,
      especially since it is the only causal therapy for erectile failure.

PMID- 9783932
TI  - Time to normalization of serum testosterone after 3-month luteinizing hormone
      releasing hormone agonist administered in the neoadjuvant setting: implications
      for dosing schedule and neoadjuvant study consideration.
AB  - PURPOSE: A time course to serum testosterone normalization after administration
      of a single 3-month luteinizing hormone-releasing hormone (LH-RH) agonist in the
      neoadjuvant setting was developed. MATERIALS AND METHODS: A total of 13 men with
      clinically localized prostate cancer were prospectively assessed for baseline
      libido, erectile function and mid morning serum testosterone. A single 3-month
      formulation LH-RH agonist was administered in the neoadjuvant setting before
      definitive treatment with radical perineal prostatectomy in 7 men or external
      beam radiotherapy in 6. Baseline and serial testosterone levels were measured 3,
      4, 6, 7, 9, 12, 15 and 18 months after injection. Symptoms related to acute
      testosterone depletion, namely hot flashes and sweats, were recorded on the same
      schedule. RESULTS: After a single 3-month LH-RH agonist injection median duration
      of castrate level testosterone (0.2 ng./ml. or less) was 6 months. Median
      duration of hypogonadal symptoms (hot flashes and sweats) was 13.6 months and
      resolution paralleled the gradual return of serum testosterone to baseline
      values. CONCLUSIONS: The 3-month formulation of LH-RH agonist administered in the
      neoadjuvant setting provides castrate level testosterone for a longer duration
      than the product labeling suggests. If confirmed, these preliminary observations
      have important implications for dosing schedule and neoadjuvant study
      consideration.

PMID- 9783933
TI  - Variability in urinary flow rate and prostate volume: an investigation using the
      placebo arm of a drug trial.
AB  - PURPOSE: We analyzed a large data set to study reproducibility of peak urinary
      flow rates and prostate volumes in benign prostatic hyperplasia patients.
      MATERIALS AND METHODS: Longitudinal data were analyzed from 284 placebo treated
      patients in a double-blind, placebo controlled benign prostatic hyperplasia drug
      trial. RESULTS: A statistically significant increase in mean maximum flow rate
      was seen in the initial 3 measurements, as well as after adjusting for voided
      volume and time between uroflows. The mean maximum flow rate increased from 8.61
      to 9.36 ml. per second at measurement 4 (8.7%). Of the patients 43% had 2
      consecutive prostate volume determinations within +/- 10%. Within patient
      variability accounted for 7% of total prostate volume variability. CONCLUSIONS:
      With subsequent voidings maximum flow rate increases in a large group of
      patients. At least 4 uroflows must be performed to reach a plateau for maximum
      flow rate. Explanations for this finding may be the increasing experience of the
      patient and regression to the mean. These findings may impact on comparison of
      large trials of treatment efficacy. Within patient variability of prostate volume
      is substantial and, in addition to measurement method and lack of reader blinding
      to time and patient identity, may be caused by other yet unknown factors.

PMID- 9783934
TI  - An open study on the efficacy and safety of transurethral needle ablation of the
      prostate in treating symptomatic benign prostatic hyperplasia: the University of
      Florida experience.
AB  - PURPOSE: We determine the safety and efficacy of transurethral needle ablation of
      the prostate in patients with moderate to severe symptoms of benign prostatic
      hyperplasia. MATERIALS AND METHODS: Transurethral needle ablation of the prostate
      was performed on 45 consecutive patients. For an average prostate of 2.5 to 3 cm.
      long treatments were performed in 2 separate planes at 4 quadrants (2, 4, 8 and
      10 o'clock positions) each. The 2 planes were 1 cm. below the bladder neck and 1
      cm. proximal to the verumontanum. For prostatic urethral lengths longer than 3
      cm. a treatment plane was added for each additional centimeter of prostatic
      urethra. The procedure was performed in 26 patients under local anesthesia using
      20 cc 2% intraurethral lidocaine gel (11) or supplemented with intravenous 1.25
      to 5 mg. midozolam (15). Of these patients 2 had a supplemental perineal block
      using a mixture of equal amounts of 15 cc 2% lidocaine without epinephrine and
      0.25% bripivacaine, 10 underwent the procedure under general anesthesia, 2 had
      epidural and 4 had spinal anesthesia, and 3 had managed anesthesia care. Mean
      length of each procedure was 79 minutes (range 50 to 240). All procedures were
      done on an outpatient basis and patients were released on the same operative day.
      RESULTS: Mean prostatic volume on transrectal ultrasound was estimated at 48.1 cc
      (range 20 to 185). Following treatment the International Prostate Symptom Score
      decreased from a mean of 20.9 at baseline to 15.4 at 1 month, 16.1 at 3 months,
      10.7 at 6 months and 9.9 at 1 year. The peak flow rate improved from a baseline
      mean of 8.3 to 13.4 at 3 months, 13.1 at 6 months and 14.9 at 1 year. The quality
      of life score improved from a baseline of 4.8 to 3.5, 2.2, 2.5 and 1.03 at 1, 3,
      6 and 12 months, respectively. Of the 2 patients in whom the procedure failed; 1
      required a bladder neck incision at 3 months and the other transurethral
      resection of the prostate. Foley catheters were left in place in all patients for
      an average of 4.85 days. CONCLUSIONS: After a followup of up to 12 months we
      conclude that transurethral needle ablation of the prostate is an effective
      treatment for symptomatic benign prostatic hyperplasia. This procedure has
      minimal morbidity, is less costly than conventional transurethral resection of
      the prostate and can be performed as an outpatient office procedure under local
      anesthesia in a significant number of patients.

PMID- 9783935
TI  - A second phase III multicenter placebo controlled study of 2 dosages of modified
      release tamsulosin in patients with symptoms of benign prostatic hyperplasia.
      United States 93-01 Study Group.
AB  - PURPOSE: In a double-blind, phase III clinical trial we evaluate the safety and
      efficacy of 0.4 and 0.8 mg. tamsulosin daily for the treatment of patients with
      symptoms of moderate to severe benign prostatic hyperplasia. MATERIALS AND
      METHODS: Patients meeting the basic requirements of the study underwent a 4-week
      single-blind placebo evaluation period. A total of 735 patients were randomized
      to double-blind therapy with tamsulosin or placebo. Treatment duration was 13
      weeks. Efficacy and safety were evaluated at 5 visits during the double-blind
      treatment period. RESULTS: When efficacy data between baseline and end point were
      compared there was a significant reduction in total American Urological
      Association symptom score (25%) in each tamsulosin group compared with placebo (p
      = 0.01) and the percentage of patients with a 30% or more reduction in peak
      urinary flow rate was significantly greater in the tamsulosin versus placebo
      group (p <0.05). Improvements in American Urological Association symptom scores
      and maximum flow rate occurred at 1 week of treatment. None of the patients
      experienced a first dose effect. There were no significant changes in blood
      pressure on standing at any visit during the study except for a decrease in
      systolic blood pressure of 20 mm. Hg or more between the 0.8 mg. dose and placebo
      groups at visit 4 (p = 0.036). Positive orthostatic tests were significantly more
      frequent in the 0.8 mg. group compared with placebo at visit 4 (p = 0.012). The
      treatment groups did not differ significantly in incidence of electrocardiogram
      abnormalities at each post-baseline visit and at end point. CONCLUSIONS:
      Tamsulosin was safe and effective, and clinically and statistically superior to
      placebo in relieving symptoms of benign prostatic hyperplasia in men with
      moderate to severe symptoms at baseline. There was no evidence of a first dose
      effect and no clinically significant orthostatic hypertension. In addition,
      response to treatment was rapid.

PMID- 9783936
TI  - Benign prostatic hyperplasia--further lessons, further problems?

PMID- 9783937
TI  - Catheter-free same day surgery transurethral resection of the prostate.
AB  - PURPOSE: Transurethral resection of the prostate using electrocautery has long
      been the standard method of management of lower urinary tract obstructive
      symptoms. While there has been a trend towards reduced catheterization time
      following transurethral prostatic resection, this study outlines the methods and
      results of transurethral prostatic resection performed in the day surgery
      setting. MATERIALS AND METHODS: The study was performed at a free-standing
      licensed day surgical hospital serving a patient population of more than 150,000.
      A total of 58 patients of a mean age of 68.77 years (range 49 to 87) underwent
      same day conventional transurethral prostatic resection. Of the procedures 39
      (67%) were performed with spinal and the remainder with general anesthesia.
      RESULTS: Mean overall duration of catheterization was 6.54 hours. Of the 48
      patients (82.76%) undergoing single catheterization mean duration was 5.59 hours.
      Mean total duration of catheterization for 10 patients (17.24%) who required
      reinsertion of a catheter was 11.09 hours. Duration of catheterization was 7.69
      hours for patients treated with spinal and 3.86 for those treated with general
      anesthesia. Repeat catheterization was required in 10 patients and was due to
      urethral discomfort in initiating micturition in 8. Postoperative urinary tract
      infections occurred in 2 patients. No patient was readmitted to the hospital for
      retention of urine but 1 was admitted to a private hospital for management of
      postoperative fever and 1 for monitoring of tachycardia. CONCLUSIONS:
      Conventional transurethral resection of the prostate can be effectively managed
      in the day surgery setting with minimal morbidity. There are significant
      advantages in reduction of catheterization time and duration of hospital stay,
      and the procedure compares favorably with new modalities.

PMID- 9783938
TI  - Grading of benign prostatic obstruction can predict the outcome of transurethral
      prostatectomy.
AB  - PURPOSE: We investigate whether urodynamic grading of benign prostatic
      obstruction and detrusor contractility predicts the outcome of transurethral
      prostatectomy. MATERIALS AND METHODS: A total of 53 patients who were suitable
      candidates for transurethral prostatectomy completed an assessment protocol
      before and 3 months after surgery, which included International Prostate Symptom
      Score, uroflowmetry, ultrasonography (prostatic size and residual urine volume)
      and standard pressure flow study. The results of the pressure flow study were
      analyzed to grade obstruction (unequivocal, equivocal or no obstruction) and
      detrusor contractility (weak or normal) using our simplified pressure flow
      nomogram. RESULTS: Analysis of the pressure flow study data demonstrated that the
      efficiency of detrusor contraction was weak in 6 of 27 men with unequivocal, 11
      of 23 with equivocal and 2 of 3 with no obstruction. Treatment outcome was
      significantly better in patients with unequivocal obstruction and normal detrusor
      contractility. Treatment failure occurred in 80% of patients with equivocal
      obstruction and impaired detrusor contractility, and 100% of the unobstructed
      group. Urodynamic grading of obstruction and detrusor contractility predicted
      treatment outcome with a sensitivity of 87%, specificity 93% and positive
      predictive value 95%. CONCLUSIONS: Urodynamic grading of benign prostatic
      obstruction and detrusor contractility can reliably predict treatment outcome
      and, therefore, enable the urologist to identify a subgroup of patients who would
      not benefit from surgery.

PMID- 9783939
TI  - The effect of prostate volume on the yield of needle biopsy.
AB  - PURPOSE: Early diagnosis of prostate carcinoma has undergone significant
      evolution mainly due to the widespread use of serum prostate specific antigen,
      transrectal ultrasonography and spring loaded biopsy devices. A common dilemma
      faced by clinicians arises when a negative biopsy is obtained in a patient and
      there is a high suspicion for prostate carcinoma. The literature reveals a 20 to
      40% positive repeat biopsy rate in men with elevated prostate specific antigen
      who had an initial negative biopsy. We determined the yield of 6 systematic
      sector biopsies as a function of total gland and peripheral zone volumes.
      MATERIALS AND METHODS: The database of transrectal ultrasound guided prostate
      needle biopsies performed at the Department of Urology, University of Washington
      Medical Center and Veterans Affairs Puget Sound Health Care System was reviewed.
      The yield of the 6 biopsies was determined as a function of the total gland and
      peripheral zone volumes. RESULTS: A total of 1,057 men who underwent transrectal
      ultrasound guided prostate needle biopsies were investigated in our study. Of the
      men 326 were diagnosed with prostate cancer for a positive biopsy rate of 30.8%.
      No relationship between gland size and cancer yield was seen using total gland
      volume compared to the first quartile until the largest quartile when a
      significantly lower cancer detection rate was noted (odds ratio 1.5).
      CONCLUSIONS: The positive yield of the systematic 6-sector biopsy decreases
      significantly when the total gland volume is greater than 55.6 cc or peripheral
      zone volume is greater than 33.61 cc. In men with smaller prostates 6 systematic
      sector biopsies should be adequate.

PMID- 9783940
TI  - Perineural invasion and seminal vesicle involvement predict pelvic lymph node
      metastasis in men with localized carcinoma of the prostate.
AB  - PURPOSE: We evaluate the contribution of perineural invasion and seminal vesicle
      biopsy results in predicting pelvic lymph node metastases in men with T1 or T2
      adenocarcinoma of the prostate. MATERIALS AND METHODS: A total of 212 men with
      localized prostate cancer were evaluated for serum prostate specific antigen
      (PSA), clinical stage, Gleason score and the presence of perineural invasion.
      Each patient had undergone seminal vesicle biopsies and a laparoscopic pelvic
      lymph node dissection before definitive therapy. The pretreatment prognostic
      values, presence of perineural invasion and seminal vesicle involvement were
      compared to the results of the laparoscopic pelvic lymph node dissection.
      Differences in proportions were tested using the Pearson chi-square test. The
      effect of multiple variables was tested using a stepwise logistic regression
      analysis. RESULTS: PSA ranged from 1.6 to 190 ng./ml. (median 11), and 52% of
      patients had Gleason score 7 or greater and 67.5% had clinical stage T2b or
      greater disease. Of the 212 patients 37 (17.5%) had perineural invasion, 43
      (20.3%) seminal vesicle involvement and 21 (10%) positive node dissections. A PSA
      greater than 20 ng./ml. (20 versus 6.8%, p = 0.006), Gleason score 7 or greater
      (15.5 versus 3.9%, p = 0.005), clinical stage T2b or greater (14 versus 0.6%, p =
      0.004), presence of perineural invasion (27 versus 6%, p = 0.0001) and seminal
      vesicle involvement (32.6 versus 4.1%, p <0.0001) influenced nodal findings.
      However, in the logistic regression model only the positive seminal vesicle
      biopsy (p = 0.0006), presence of perineural invasion (p = 0.04) and PSA greater
      than 20 ng./ml. (p = 0.044) were significant variables. Of the 21 men with
      positive node dissections 18 (85.7%) had a positive seminal vesicle biopsy or
      perineural invasion. Separation of patients into a high risk group defined by a
      positive seminal vesicle biopsy or perineural invasion, or a low risk group
      defined as the absence of these features yielded a significant association with
      nodal involvement (28 versus 2%, p <0.0001). A separate analysis of the patients
      with a negative seminal vesicle biopsy demonstrated that only perineural invasion
      (19 versus 2%, p = 0.0002) and PSA greater than 20 ng./ml. (12 versus 2%, p =
      0.01) conferred a greater risk of nodal metastases. A logistic regression
      analysis in the negative seminal vesicle biopsy group discarded all of the
      variables other than perineural invasion as significant. CONCLUSIONS: A positive
      seminal vesicle biopsy is the most significant predictor of pelvic lymph node
      metastases in men with T1 or T2 prostate cancer. Perineural invasion is also an
      independent predictor of nodal disease. Patients with either of these features
      should undergo pelvic lymph node dissection before receiving definitive therapy.

PMID- 9783941
TI  - Site specific predictors of positive margins at radical prostatectomy: an
      argument for risk based modification of technique.
AB  - PURPOSE: We identify patients at high risk for positive bladder neck, apical or
      posterior margins who may benefit from technical modifications, such as excision
      of the bladder neck or wide excision of the neurovascular bundles. MATERIALS AND
      METHODS: We studied 242 patients with clinically localized prostate cancer
      undergoing radical prostatectomy with or without neoadjuvant androgen deprivation
      therapy between June 1992 and August 1997 who had a sextant biopsy available for
      review. Multivariate logistic regression analysis was used to develop models for
      prediction of positive bladder neck, apical, and right and left posterior margins
      based on clinical parameters. From these models patients at low and high risk for
      positive margins were identified. RESULTS: The incidence of positive margins was
      36% with 69% solitary sites. Patients with a prostate specific antigen of greater
      than 10 ng./ml. had a higher incidence (16%) of positive bladder neck margins.
      Patients with 3 or more positive cores who did not receive neoadjuvant androgen
      deprivation therapy had a higher incidence (24%) of positive apical margins. A
      nomogram incorporating pretreatment serum prostate specific antigen, number of
      ipsilateral positive cores and whether androgen deprivation therapy was used
      identified patients at high risk for positive posterior margins. CONCLUSIONS: The
      nomograms presented identify patients at high risk for positive margins at
      various sites who may benefit from modification of surgical technique based on
      risk.

PMID- 9783942
TI  - Use of lower prostate specific antigen cutoffs for prostate cancer screening in
      black and white men.
AB  - PURPOSE: We evaluated differences in the prostate cancer detection rate among
      black and white men with serum prostate specific antigen (PSA) levels between 2.6
      and 4.0 ng./ml., and benign findings on digital rectal examination. MATERIALS AND
      METHODS: From May 1995 through June 1997 we screened 14,209 white and 1,004 black
      men 50 years old or older with serum PSA and rectal examinations at 6-month
      intervals. If PSA was greater than 2.5 ng./ml. or the rectal examination was
      suspicious for cancer, we recommended an ultrasound guided sextant biopsy of the
      prostate. We compared differences in clinical characteristics, compliance with
      the recommendation for biopsy, cancer detection rate, and stage and grade of
      tumors detected for 924 white and 57 black men. RESULTS: Black men were younger
      (60 versus 63 years old, p = 0.005) and presented with slightly higher PSA levels
      (3.3 versus 3.1 ng./ml., p = 0.03) than white men. Overall cancer detection rate
      was 27% (106 of 391 patients), with cancer detection 2-fold higher among black
      (13 of 29, 45%) than among white (93 of 362, 26%) men (p = 0.03, odds ratio 2.4,
      95% confidence interval 1.1 to 5.1). Controlling for age, total PSA, PSA density,
      percent free PSA and number of prior screening visits, race remained a
      significant predictor of cancer (adjusted odds ratio 3.4, confidence interval 1.4
      to 8.4). We found trends for worse pathological stage and grade among black men
      but these differences did not reach statistical significance. CONCLUSIONS: Black
      race was an independent predictor of prostate cancer even at lower PSA cutoffs
      (2.6 to 4.0 ng./ml.). Although the positive predictive value for cancer detection
      was relatively high in black men, long-term outcomes studies are necessary to
      determine whether the use of lower PSA cutoffs would result in favorable shifts
      in cancer stage and grade, and a reduction in racial differences in prostate
      cancer mortality rates.

PMID- 9783943
TI  - Towards a better crystal ball.

PMID- 9783944
TI  - The usefulness of touch preparation cytological evaluation and prostatic capsule
      involvement in prediction of prostate cancer recurrence.
AB  - PURPOSE: Touch preparation cytology has been used in oncology as a technique to
      assist in predicting local tumor recurrence. We prospectively investigated the
      relationship between this cytological evaluation and the standard histological
      method of assessing specimens, measuring the distance from the tumor to the
      various anatomical boundaries and disease recurrence in radical retropubic
      prostatectomy patients. MATERIALS AND METHODS: In a prospective study of 91
      consecutive clinical stages T1c and T2 cancer cases radical retropubic
      prostatectomy touch preparation cytology was performed intraoperatively in an
      anatomical fashion (apex, posterior, lateral right and left, and base). A single
      blinded cytopathologist reviewed all prostate touch preparation specimens and
      categorized them as malignant, benign or atypical cells. Benign or atypical cells
      were classified as negative cytology. Detailed histological margin analysis of
      the surgical specimens was also done in which distances between the tumor front,
      and prostate capsule (inner and outer edge) and surgical margins (apex,
      posterior, right and left lateral, and base) were measured. All specimens were re
      staged by the same pathologist. Median followup was 38 months. Disease recurrence
      was determined biochemically (prostate specific antigen), and with bone scans,
      prostatic fossa biopsies and digital rectal examinations. RESULTS: Of the 91
      specimens 25 were excluded from study because distance measurements could not be
      made for technical reasons. Multivariate analysis was performed on the remaining
      66 patients based on the variables of stage, age, cytology status, distance from
      tumor to the inner prostatic capsule, distance from tumor to the surgical margin
      and postoperative Gleason sum. The only variable with independent prognostic
      value was postoperative Gleason sum (p = 0.04). Cytology status was not
      statistically significant (p = 0.07) nor were distance data to the inner capsule
      (p >0.05) and surgical margin (p >0.05). CONCLUSIONS: Although touch preparation
      cytology does not enhance prognostic information already provided by Gleason sum,
      it does correlate highly with postoperative Gleason sum. Other gross macroscopic
      variables, that is pathological stage, margin status and distance measurements,
      although lacking in independent predictive value, correlated with postoperative
      Gleason sum. The constancy of Gleason sum leads us to believe that the key to
      predicting prostatic cancer behavior lies not on the macroscopic but on the
      molecular or cellular level. Of the various factors analyzed in this study
      postoperative Gleason sum remains the most powerful predictor of recurrence risk.

PMID- 9783945
TI  - Radiation therapy for the management of biopsy proved local recurrence after
      radical prostatectomy.
AB  - PURPOSE: We determine which clinical characteristics correlate with a successful
      outcome following external beam radiation for the management of biopsy proved,
      locally recurrent prostate cancer after radical prostatectomy. MATERIALS AND
      METHODS: The clinical records of 34 patients who were treated at our institution
      with external beam radiation for biopsy proved local disease recurrence after
      radical prostatectomy were reviewed. Mean followup was 77.9 months after radical
      prostatectomy and 38.3 months after radiotherapy. Preoperative, postoperative and
      pathological characteristics were examined for the ability to predict failure
      following radiotherapy. RESULTS: Of the 34 patients 9 (26%) exhibited
      persistently low and stable serum prostate specific antigen (PSA) (less than 0.5
      ng./ml.), while 7 (21%) had an undetectable serum PSA (less than 0.1 ng./ml.)
      during followup. These 16 patients were considered to be successfully treated by
      radiation and in the remaining 18 (53%) radiation was considered to have failed.
      The likelihood of successful treatment at 3 years after radiotherapy for all
      patients was 48%. Preoperative PSA, PSA at first elevation, postoperative PSA
      velocity and pathological stage were not significant predictors of a successful
      outcome following radiation treatment. Patients with a serum PSA of 4 ng./ml. or
      less before receiving radiotherapy and those with a prostatectomy specimen
      Gleason score of 7 or less were significantly more likely to be successfully
      treated by radiotherapy. CONCLUSIONS: Radiation therapy is a viable treatment
      option for select patients with biopsy proved local disease recurrence following
      radical prostatectomy. The chance of achieving and maintaining a persistently low
      and stable or undetectable serum PSA is likely in those patients with a
      prostatectomy specimen Gleason score of 7 or less and a pre-radiation PSA of 4.0
      ng./ml. or less. More effective treatment regimens are needed for those patients
      in whom radical prostatectomy fails.

PMID- 9783946
TI  - Neoadjuvant androgen ablation for localized prostatic cancer: pathology methods,
      surgical end points and meta-analysis of randomized trials.
AB  - PURPOSE: At least 7 centers or collaborative groups have performed randomized
      clinical trials of neoadjuvant androgen ablation and radical prostatectomy versus
      radical prostatectomy alone for localized prostatic cancer. Our objectives were
      to analyze treatment results in terms of 2 standard outcome measures, to identify
      patient characteristics and other factors that explain outcome differences
      between trials, and to use pooled data to test the hypothesis that neoadjuvant
      treatment alters outcomes. MATERIALS AND METHODS: Trials were identified by
      MEDLINE search and review of published bibliographies, and examined for
      pathological techniques used to assign surgical end points. An attempt was made
      to contact trial group members for clarification and updated information. The
      resulting data were transformed as needed into standardized end points of pT
      stage and negative surgical margin. A series of contingency tables were used to
      study relationships between treatment outcomes and various risk factors. RESULTS:
      In addition to neoadjuvant treatment, numerous risk factors related to treatment
      regimen and patient characteristics apparently influenced treatment outcome, and
      should be reanalyzed when future followup trial data become available.
      CONCLUSIONS: In radical prostatectomy there is a need for uniform ways to process
      specimens, assign surgical stage and establish standardized surgical end points.
      Despite differences in risk factors, the trials were similar in overall design.
      Within these constraints neoadjuvant androgen ablation was significantly
      associated with low pT stage and negative surgical margin. Longer followup is
      needed to validate these measures as good surrogates for tumor specific survival.

PMID- 9783947
TI  - Pain and quality of life following radical retropubic prostatectomy.
AB  - PURPOSE: We assess pain and quality of life following radical retropubic
      prostatectomy and determine whether intraoperative anesthetic management has any
      long-term effects on outcomes. MATERIALS AND METHODS: A total of 110 patients
      undergoing radical retropubic prostatectomy were randomly assigned to receive
      epidural and/or general anesthesia. Patients responded to a questionnaire mailed
      3 and 6 months following surgery that assessed prostate symptoms, pain related to
      surgery, quality of life and mood. RESULTS: No long-term effects of anesthesia
      were observed. Of the 103 respondents (94%) at 3 months 49% had some pain related
      to surgery. Although pain was not related to anesthesic technique, patients who
      had it at 3 months used significantly more pain medication on postoperative day
      3. Pain at 3 months was mild, averaging 1.5 on a scale of 0 to 10, and associated
      with poor perceptions of overall health (p <0.02), and reduced physical (p <0.01)
      and social (p <0.01) functioning. Pain at 3 months was associated with higher
      levels of preoperative anxiety (p <0.05). At 6 months 36 of 90 patients (35%) had
      some pain related to surgery and the impact was similar. CONCLUSIONS: Long-term
      effects of intraoperative anesthesic technique were not apparent. Mild pain
      following radical retropubic prostatectomy was common and associated with reduced
      quality of life, particularly social functioning. Affective distress,
      particularly anxiety, before surgery and use of pain medications following
      surgery may be predictors of chronic pain following radical retropubic
      prostatectomy.

PMID- 9783948
TI  - Quality of life in metastatic prostate cancer among men of lower socioeconomic
      status: feasibility and criterion related validity of 3 measures.
AB  - PURPOSE: Identification of metastatic disease progression is often difficult but
      important. Previous studies of quality of life in metastatic disease have been
      limited by the small number of respondents who were not white or of lower
      socioeconomic status. Quality of life assessment is generally done using self
      administration techniques but this method is of limited usefulness for patients
      of low socioeconomic status, many of whom have limited reading abilities. We
      evaluated the feasibility and validity of interviewer administration of 3 quality
      of life instruments for patients of low socioeconomic status with metastatic
      prostate cancer. MATERIALS AND METHODS: We used instruments previously validated
      with self-administration methodology, including the European Organization for
      Research and Treatment of Cancer-Quality of Life Questionnaire-30, Functional
      Assessment of Cancer Therapy-General Scale and Quality of Life Index. Subjects
      were men with metastatic prostate cancer with stable (78) or progressive (32)
      disease at 4 Veterans Affairs medical centers and 1 other site. Of the patients
      94% were Veterans Affairs patients and more than 60% were black. RESULTS: Each
      quality of life instrument required less than 10 minutes of interviewer
      administration and was able to discriminate between patients with stable versus
      progressive disease on several health status domains. CONCLUSIONS: These data
      support the feasibility and validity of quality of life measurement in patients
      of low socioeconomic status with metastatic prostate cancer. Consideration should
      be given to adding quality of life instruments to patient encounter even among
      low socioeconomic status, low literacy populations.

PMID- 9783949
TI  - Combination chemotherapy for metastatic or locally advanced genitourinary
      squamous cell carcinoma: a phase II study of methotrexate, cisplatin and
      bleomycin.
AB  - PURPOSE: The prognosis of patients with advanced squamous cell carcinoma of
      genitourinary origin is poor. While single agent chemotherapy results mainly in
      partial responses of short duration, data on the efficacy of combination
      chemotherapy are extremely limited. We determined the response rate and toxicity
      of a combination of 3 of the most active agents, methotrexate, cisplatin and
      bleomycin, in patients with advanced genitourinary squamous cell carcinoma.
      MATERIALS AND METHODS: Patients with metastatic or locally advanced genitourinary
      squamous cell carcinoma were eligible for study. Treatment consisted of 200
      mg./m.2 methotrexate on days 1, 15 and 22, and 20 mg./m.2 cisplatin and 10
      mg./m.2 bleomycin on days 2 through 6 during a 28-day cycle. RESULTS: Of the 30
      patients who enrolled in the trial 29 were evaluable for response. Objective
      response was achieved in 16 patients (55%, 95% confidence interval 36 to 72), 4
      of whom achieved a complete response (14%). Median objective response duration
      was 4.7 months (range 1.9 to 39.5). Median survival of the entire group was 11.5
      months (range 1.5 to 87.0). Of the patients 9 achieved disease-free status,
      including 6 following consolidation surgery or radiation therapy. Median survival
      of these 9 patients (34.4 months, range 9.6 to 87.0) was significantly greater (p
      = 0.0003) than that of patients who did not become disease-free (7.0 months,
      range 1.5 to 38.6). Grade III or IV hematological toxicity in 116 courses
      included neutropenia (13%) and thrombocytopenia (6%). Among 30 patients evaluable
      for toxicity serious nonhematological toxic effects included stomatitis (3%) and
      renal toxicity (7%). There was 1 death from neutropenic sepsis. CONCLUSIONS:
      Methotrexate, cisplatin and bleomycin combination chemotherapy for genitourinary
      squamous cell carcinoma results in a high but short lived overall response rate,
      and a low complete response rate with manageable toxicity. A multidisciplinary
      approach to achieve disease-free status may provide the best opportunity to
      effect survival and should be the focus of future trials.

PMID- 9783950
TI  - Prevalence of and risk factors for latex sensitization in patients with spina
      bifida.
AB  - PURPOSE: We determined the prevalence of and risk factors for latex sensitization
      in patients with spina bifida. MATERIALS AND METHODS: A total of 59 consecutive
      subjects 2 to 40 years old with spina bifida answered a questionnaire, and
      underwent a latex skin prick test and determination of serum IgE specific for
      latex by RAST CAP radioimmunoassay. We also noted the relationships of total
      serum IgE skin prick tests to common air and food allergens. In addition, skin
      prick plus prick tests were also done with fresh foods, including kiwi, pear,
      orange, almond, pineapple, apple, tomato and banana. RESULTS: Latex sensitization
      was present in 15 patients (25%) according to the presence of IgE specific to
      latex, as detected by a skin prick test in 9 and/or RAST CAP in 13. Five latex
      sensitized patients (33.3%) had clinical manifestations, such as urticaria,
      conjuctivitis, angioedema, rhinitis and bronchial asthma, while using a latex
      glove and inflating a latex balloon. Atopy was present in 21 patients (35.6%). In
      14 patients (23%) 1 or more skin tests were positive for fresh foods using a
      prick plus prick technique. Tomato, kiwi, and pear were the most common skin test
      positive foods. Univariate analysis revealed that a history of 5 or more
      operations, atopy and positive prick plus prick tests results for pear and kiwi
      were significantly associated with latex sensitization. Multivariate analysis
      demonstrated that only atopy and a history of 5 or more operations were
      significantly and independently associated with latex sensitization. CONCLUSIONS:
      A fourth of the patients with spina bifida were sensitized to latex. Atopy and an
      elevated number of operations were significant and independent predictors of
      latex sensitization in these cases.

PMID- 9783951
TI  - A technique for the transplantation of 2 adult cadaver kidney grafts into 1
      recipient.

PMID- 9783952
TI  - Expeditious method of difficult ureteral stent change with preservation of
      ureteral access.

PMID- 9783953
TI  - A surgical technique combining continent cutaneous urinary diversion and complete
      ileal ureteral replacement.
AB  - PURPOSE: Defects of the entire urinary tract are sometimes so extensive that a
      colonic conduit appears to be the only viable therapeutic option. However, if an
      incontinent diversion is unacceptable, an alternative must be found. MATERIALS
      AND METHODS: We report on a new technique for achieving a continent diversion in
      which ileocecal intestinal segments are used as a continent reservoir and
      substitute for both ureters. RESULTS: At 2-year followup excellent results were
      achieved in terms of renal function, continence and quality of life as confirmed
      by symptomatic evaluation and radiographic investigations. CONCLUSIONS: We
      demonstrate the feasibility of reconstruction of the entire urinary tract with a
      continent reservoir using intestinal segments with a pure colonic pouch and
      prevalvular ileal segment as a substitute for both ureters.

PMID- 9783954
TI  - Development of noninvasive velocity flow video urodynamics using Doppler
      sonography. Part I: Experimental urethra.
AB  - PURPOSE: We believed that a totally noninvasive video urodynamic system could be
      invented based on the concept of Doppler ultrasonography. To develop this system
      we measured flow velocity in an experimental urethra using 4 materials, including
      natural urine. MATERIALS AND METHODS: A cellulose tube was inserted into a
      standoff pad as an experimental urethra. Degassed water, distilled water, urine
      and liposome (multi-lamellar particles) solution comprised the 4 materials used
      to compare signal intensity and flow velocity at various flow rates. The flow
      rate from the tube was measured with a uroflowmeter. The Doppler image and
      digital uroflow signal data were processed by a computer. RESULTS: Doppler
      signals and flow velocity curves could be sufficiently obtained using distilled
      water, urine and liposome solution, while degassed water showed no Doppler
      signals at any flow rate. Minimum flow rate at which clear Doppler signals were
      continuously detected from the angle in the frontal plane was greater than 3.0
      ml. per second for distilled water, greater than 1.5 for urine and greater than
      0.3 for liposome solution. Maximum flow velocities were identical in these 3
      materials at a flow rate of greater than 2.0 ml. per second. The functional cross
      sectional area of the tube showed a constant value irrelevant to the initial flow
      rate. CONCLUSIONS: Flow velocity could be measured by Doppler ultrasound above a
      certain minimal flow rate. Dissolved gasses have an important role in creating
      Doppler signals. Flow velocity, velocity related parameters and functional cross
      sectional area can diagnose and localize the area of bladder outlet obstruction.
      Liposome solution may be helpful in detecting velocity in low flow states in
      future systems.

PMID- 9783956
TI  - Renal cell carcinoma presenting as vaginal bleeding.

PMID- 9783957
TI  - Hypercalcemia associated with squamous cell carcinoma of the renal pelvis.

PMID- 9783955
TI  - Development of noninvasive velocity flow video urodynamics using Doppler
      sonography. Part II: clinical application in bladder outlet obstruction.
AB  - OBJECTIVES: We have developed a totally noninvasive urodynamic technique based on
      the concept of Doppler sonography, which was tested in men with and without
      bladder outlet obstruction. MATERIALS AND METHODS: An ultrasonic image directed
      Doppler system with a 3.75 MHz. micro-convex electro-probe was operated
      transperineally using a specially devised remote control robotic holder. Uroflow
      rates from the urethral meatus were also measured with a flowmeter. The color
      Doppler ultrasound image and digital flow velocity data were processed by a
      personal computer. Color scale data were analyzed by customized software.
      Multiple rectangle sample volumes could be set in any size in any position, and
      the resulting color encoded data were averaged. Calculation was performed every
      0.5 second and a flow velocity curve in the region of interest was obtained. A
      total of 12 men, 6 without (controls) and 6 with bladder outlet obstruction, were
      evaluated by conventional pressure flow study and the new Doppler ultrasound
      urodynamic system. Bladder outlet obstruction was determined using the nomogram
      of Abrams and Griffiths. The sample volume for a flow velocity curve was set only
      in the prostatic urethra and, thus, maximum flow velocity in and functional cross
      sectional area of the prostatic urethra were determined. RESULTS: Urinary stream
      in the male urethra was clearly detected and flow velocity in the prostatic
      urethra could be measured in all cases. Maximum flow rate measured by a flowmeter
      was significantly lower in the bladder outlet obstruction group. Maximum flow
      velocity by Doppler study was almost the same in the obstructed and control
      groups. Functional cross-sectional area, which was calculated by dividing maximum
      flow rate by maximum flow velocity, was lower in the bladder outlet obstruction
      (mean plus or minus standard deviation 0.31+/-0.16 cm.2) than control group
      (0.78+/-0.23 cm.2) (p = 0.006). Velocity flow plots were possible in both groups.
      CONCLUSIONS: The concept of noninvasive pressure flow-like urodynamic evaluation
      based on Doppler ultrasound is feasible. Parameters of flow velocity as well as
      functional cross-sectional area can be used in the diagnosis of bladder outlet
      obstruction and to localize the site of obstruction.

PMID- 9783958
TI  - Two cases of nonocclusive mesenteric ischemia after radical cystectomy.

PMID- 9783959
TI  - Primary lymphoma of the epididymis.

PMID- 9783960
TI  - Massive prostatic bleeding after transurethral resection of the prostate in a
      patient with a congenital pelvic arteriovenous malformation.

PMID- 9783961
TI  - 1997 American Urological Association Gallup survey: Changes in diagnosis and
      management of prostate cancer and benign prostatic hyperplasia, and other
      practice trends from 1994 to 1997.
AB  - PURPOSE: The American Urological Association first commissioned the Gallup
      Organization to conduct a study to assess urologist practice patterns in 1992. We
      present the results of the 1997 survey, the sixth consecutive Gallup survey
      performed for the Association. MATERIALS AND METHODS: A random sample of 502
      American urologists who had completed urological residency and practiced at least
      20 hours weekly in 1996 was interviewed by telephone in February and March 1997.
      RESULTS: Emerging trends showed significant changes since 1994 in how urologists
      diagnosed and treated prostate cancer. The survey revealed a significant change
      in the tests routinely ordered to stage newly diagnosed prostate cancer and for
      diagnostic evaluation of patients with benign prostatic hyperplasia. CONCLUSIONS:
      Urologists are becoming more cost conscious and effective in ordering
      pretreatment testing. Urologists are becoming more oriented toward medical
      treatment for the management of benign prostatic hyperplasia, and less laser
      surgery is being performed.

PMID- 9783962
TI  - Re: Interleukin-2 in T1 papillary bladder carcinoma: regression of the marker
      lesion in 8 of 10 patients.

PMID- 9783963
TI  - Re: Editorial: Primary nocturnal enuresis--an analysis of factors related to its
      etiology.

PMID- 9783964
TI  - Re: Osteoporosis after orchiectomy for prostate cancer.

PMID- 9783965
TI  - Role of the renin-angiotensin system in disorders of the urinary tract.
AB  - PURPOSE: The role of the renin-angiotensin system in the homeostasis of fluid,
      electrolyte and blood pressure has been known for quite some time. Recent
      developments indicate that angiotensin has a profound role, not only in the
      developing urinary tract but also in the response of the urinary tract to injury.
      In this review we outline these characteristics. MATERIALS AND METHODS: We
      summarize the clinical approach to congenital abnormalities of the kidney and
      urinary tract, and report new data obtained in genetically engineered mice.
      Furthermore, we present the connection between the mutant mice observations and
      human congenital abnormalities. RESULTS: Genetically engineered mutants clearly
      indicate that the renin-angiotensin system is important for normal renal and
      urological development. As in glomerular disease, the renin-angiotensin system is
      involved in progressive damage due to urological disease. CONCLUSIONS: While the
      renin-angiotensin system is important for blood pressure regulation, it also
      affects the embryogenesis of the urinary tract and modulates renal injury due to
      specific disease processes. The importance of angiotensin and its blockade
      provides an exciting avenue for possible early treatment in children with
      congenital anomalies of the kidney and urinary tract.

PMID- 9783966
TI  - Comparison of sonicated albumin enhanced sonography to fluoroscopic and
      radionuclide voiding cystography for detecting vesicoureteral reflux.
AB  - PURPOSE: We compared sonicated albumin enhanced sonography to fluoroscopic and
      radionuclide voiding cystography for detecting vesicoureteral reflux. MATERIALS
      AND METHODS: After obtaining informed consent we enrolled in our study 20
      patients with known or suspected vesicoureteral reflux and no contraindications
      to intravesical sonicated albumin. All patients underwent albumin enhanced
      sonography, following which 10 patients each underwent radionuclide and
      fluoroscopic voiding cystography. Reflux was graded by the observing radiologist
      and urologist. RESULTS: In 10 patients albumin enhanced sonography demonstrated
      reflux in 6 of the 7 (83%) ureters in which radionuclide cystography identified
      reflux. In 2 patients ultrasound studies were inadequate due to excessive
      movement during the procedure, and the patients were classified as unevaluable.
      In the remaining 10 patients 12 of 20 ureters (60%) were equal in the absence or
      presence of and degree of reflux on enhanced sonography and voiding
      cystourethrography. In 6 ureters voiding cystourethrography detected reflux more
      readily or revealed a higher grade of reflux. Two ureters had a higher reflux
      grade on enhanced sonography. No adverse effects were associated with
      intravesical sonicated albumin. CONCLUSIONS: In experienced hands sonicated
      albumin enhanced sonography is safe for evaluating vesicoureteral reflux. It
      provides the simultaneous evaluation of renal contours, parenchyma and size in
      addition to bladder visualization. This new technique may prove to be useful as a
      followup study in patients with previously documented reflux or as a primary
      study for sibling screening.

PMID- 9783967
TI  - The impact of treated dysfunctional voiding on the nonsurgical management of
      vesicoureteral reflux.
AB  - PURPOSE: We evaluated the impact of dysfunctional voiding on the nonsurgical
      management of vesicoureteral reflux in toilet trained children. MATERIALS AND
      METHODS: The study population comprised 107 girls and 21 boys 3 to 10 years old
      who were diagnosed with vesicoureteral reflux during evaluation for urinary tract
      infection or dysfunctional voiding. Dysfunctional voiding was identified
      prospectively on the basis of typical symptoms. All patients with a urinary tract
      infection received antibiotic prophylaxis and oxybutynin was prescribed for all
      those with dysfunctional voiding. Girls with dysfunctional voiding who had no
      history of urinary tract infection were also given daily antibiotic prophylaxis.
      RESULTS: Of the 128 patients 51 girls and 15 boys had dysfunctional voiding.
      Reflux spontaneously resolved in 27 of the 44 evaluable girls (61%) with normal
      and 19 of the 42 (45%) with dysfunctional voiding. A breakthrough urinary
      infection developed in 18 girls (43%) with versus only 5 (11%) without
      dysfunctional voiding (p = 0.001). No boys had a breakthrough infection.
      CONCLUSIONS: Despite anticholinergic therapy and antibiotic suppression 43% of
      the girls with dysfunctional voiding in whom reflux may otherwise have resolved
      spontaneously had a breakthrough urinary infection leading to surgery.

PMID- 9783968
TI  - Ureteral tissue expansion for bladder augmentation: a long-term prospective
      controlled trial in a porcine model.
AB  - PURPOSE: We recently described a technique that iatrogenically produces segmental
      megaureter while preserving renal function. In our initial report in 5 of 8 pigs
      that underwent this procedure bladder augmentation with the expanded ureter was
      successful. Throughout the expansion and reconstructive process renal function
      was preserved and all 5 animals that underwent augmentation had increased bladder
      capacity at sacrifice 1 month postoperatively. In the present study we evaluated
      the long-term durability and performance of the ureteral segment used for
      augmentation. MATERIALS AND METHODS: We performed a prospective, controlled,
      double armed study in 8 pigs, including 4 control animals that underwent subtotal
      cystectomy only (group 1) and 4 animals that underwent subtotal cystectomy
      followed by bladder augmentation using the expanded ureteral segment (group 2).
      End point measurements included cystography, and measurement of bladder capacity,
      serum creatinine and random bladder residual urine volumes. All cystograms were
      performed using passive filling conditions at a standard filling pressure of 32
      cm. water. RESULTS: Bladder capacity throughout the study revealed consistently
      higher volumes in group 2 than in group 1. In 3 of the 4 group 1 subjects
      vesicoureteral reflux developed compared to no reflux in group 2. Creatinine
      levels were elevated at sacrifice in 50% of the animals in group 1 compared to
      none in group 2. Random bladder residual urine was less than 150 cc in 3 of the 4
      group 2 subjects. CONCLUSIONS: Serial cystograms in pigs after ureteral
      augmentation suggest that the tissue does not contract with time. Animals that
      underwent ureteral augmentation had significantly greater bladder capacity than
      controls. Random bladder residual urine volume remained low throughout the study
      period. Ureteral tissue expansion for bladder augmentation appears to be feasible
      and durable in this animal model. In addition, it may be protective against the
      deleterious effects associated with small capacity bladders.

PMID- 9783969
TI  - Urethral duplication in children: surgical treatment and results.
AB  - PURPOSE: Urethral duplication is a rare congenital anomaly. We report the
      clinical presentation, imaging findings and surgical treatment in 7 boys with
      incomplete sagittal duplication of the urethra. MATERIALS AND METHODS:
      Duplication involved hypospadias in 5 cases (group 1) and a bifid urethra with an
      accessory preanal tract (Y duplication) in 2 (group 2). Group 1 was treated with
      1-stage urethroplasty, including marsupialization of the dorsal orthotopic
      urethra, ventral-to-dorsal urethrourethrostomy and penile island flap onlay
      repair to cover the open dorsal urethra. In contrast, group 2 was treated with 2
      stage urethral reconstruction with detachment and mobilization of the accessory
      preanal branch in association with a scrotal tubed neourethra followed by
      urethroplasty, as in group 1. In all cases the dorsal penile urethra was located
      between the corpora cavernosa and surrounded by the tunica albuginea. RESULTS: A
      urethrocutaneous fistula developed in 1 of the 5 group 1 patients. In group 2, 1
      patient had recurrent penoscrotal meatal stenosis after the 1-stage procedure and
      1 had a urethral diverticulum with calculi at the scrotal tubed neourethra 7
      years after urethral reconstruction. Six of the 7 patients now void spontaneously
      through a meatus located normally at the tip of the glans. The remaining patient
      with a neurogenic bladder is on intermittent catheterization via
      appendicovesicostomy due to difficult catheterization of the irregular and
      sensitive neourethra. CONCLUSIONS: While the ideal surgical management of
      urethral duplication anomalies remains uncertain, we used a combination of
      surgical techniques to correct this severe malformation.

PMID- 9783970
TI  - Antisperm antibodies in cryptorchidism before and after surgery.
AB  - PURPOSE: We verified the prevalence of serum antisperm antibodies at diagnosis in
      a large group of cryptorchid boys, and determined whether it may be influenced by
      orchiopexy. MATERIALS AND METHODS: We prospectively evaluated serum antisperm
      antibodies in 186 and 23 boys 0.67 to 14.25 years old with unilateral and
      bilateral cryptorchidism, respectively, before, and 3, 12 and 24 months after
      surgery. At diagnosis Tanner stage was 1 and 2 or 3 in 188 and 21 cases,
      respectively. During the 2-year followup 23 boys entered puberty. A total of 111
      normal prepubertal (Tanner stage 1) and 54 pubertal (Tanner stage 2 or 3) boys
      served as controls. Antisperm antibodies were detected using the tray
      agglutination and indirect immunobead tests. RESULTS: At diagnosis 29 cryptorchid
      boys (13.8%) were antisperm antibody positive, including 21 of the 188
      prepubertal (11.1%) and 8 of the 21 pubertal (38%) boys (significantly different,
      chi-square test p <0.001). In 27 cases the tray agglutination test was positive
      with titers between 1:16 and 1:512, in 18 the indirect immunobead test was
      positive for IgG with titers between 1:10 and 1:100, and in 16 both tests were
      positive. There was no statistical difference when antisperm antibody results
      were analyzed for unilateral and bilateral cryptorchidism or testis location. All
      normal boys were antisperm antibody negative. During the 2-year followup
      antisperm antibodies appeared in 1 previously negative case, and the antibody
      titer increased to 128 to 512 in the tray agglutination and to 1:100 in the
      indirect immunobead tests in 4 positive cases. In all of these cases pubertal
      changes were also observed. CONCLUSIONS: Our study indicates that cryptorchidism
      may elicit an autoimmune response against sperm antigen in childhood independent
      of testis location and orchiopexy. Moreover, patients of pubertal age appear to
      be at higher risk for antisperm antibody development.

PMID- 9783971
TI  - Tumors of the adrenogenital syndrome: an aggressive conservative approach.
AB  - PURPOSE: Testicular masses in male individuals with the adrenogenital syndrome
      are a clinical and pathological diagnostic dilemma. The major differential
      diagnosis of gonadal nodules in this setting includes interstitial Leydig cell
      tumors and secondary benign tumors of possible adrenal rest origin. Management of
      these 2 entities obviously differs. We report clinical, biochemical and
      pathological features in 3 children with rare bilateral testicular masses and the
      adrenogenital syndrome in an attempt to define better the natural history of
      these entities and formulate recommendations for management. MATERIALS AND
      METHODS: All 3 patients had a history of precocious puberty. Two boys were
      diagnosed with the adrenogenital syndrome at birth, and presented with bilateral
      testicular masses at ages 5 and 17 years, respectively. The remaining patient was
      diagnosed at age 15 years after testicular and adrenal masses developed. All 3
      cases were classified as 21-hydroxylase deficiency with markedly elevated levels
      of 17-hydroxyprogesterone, dehydroepiandrosterone, adrenocorticotropic hormone
      and androstenedione. Testosterone levels were mildly elevated above normal age
      matched values. Testicular biopsies were done in each case. RESULTS: Two cases
      were initially interpreted as bilateral Leydig cell tumors but they were
      histologically reclassified as tumors of the adrenogenital syndrome. The other
      case was diagnosed as interstitial cell hyperplasia. Although corticosteroid
      therapy corrected each steroid abnormality, in no case did tumors resolve, but
      there was gradual regression in 1. Each patient has been followed conservatively
      for 4 years. There has been no increase in tumor size or evidence of metastatic
      disease. CONCLUSIONS: Bilateral testicular masses in children with the
      adrenogenital syndrome may mimic Leydig cell tumors, which also commonly cause
      precocious puberty. Orchiectomy for Leydig cell tumors in boys with precocious
      puberty is contraindicated without a complete endocrinological profile. When
      congenital adrenal hyperplasia is diagnosed, these tumors appear to be derived
      from cells of possible adrenal origin stimulated by adrenocorticotropic hormone
      and they may be followed conservatively.

PMID- 9783972
TI  - Epididymitis in children: the circumcision factor?
AB  - PURPOSE: Recommendations for circumcision have significantly altered in the last
      several years. Studies have objectively established an increased risk of urinary
      tract infection in uncircumcised boys. We evaluated the relationship between
      epididymitis and circumcision status. MATERIALS AND METHODS: We studied the
      relationships among the circumcision status of 36 consecutive boys with
      epididymitis in a review of 128 with acute scrotal inflammation (group 1),
      circumcision status of 43 in whom the diagnosis of epididymitis at discharge home
      had been made elsewhere (group 2), New York State hospital discharge figures for
      circumcision in newborns (group 3) and the regional prevalence of circumcision in
      200 consecutive pediatric emergency department patients at the same institution
      with nonurological diagnoses (group 4). RESULTS: New York State Department
      figures indicate that 70% of male newborns are discharged home with a hospital
      code for circumcision. Similarly an evaluation of 200 consecutive male patients
      without urological diagnoses younger than 18 years in the emergency department
      revealed that 131 (65%) were circumcised. Comparatively in groups 1 and 2 only 25
      and 26% of patients, respectively, were circumcised. The statistical difference
      in circumcision status among the 4 groups was significant (p >0.0004).
      CONCLUSIONS: These data demonstrate with highly statistical significance that a
      relationship exists between epididymitis and the presence of a foreskin. We found
      that an intact foreskin is an important etiological factor in boys with
      epididymitis.

PMID- 9783973
TI  - Androgen responsiveness of stromal cells of the human prostate: regulation of
      cell proliferation and keratinocyte growth factor by androgen.
AB  - PURPOSE: Growth and development of the prostate are androgen dependent and mainly
      influenced by stromal-epithelial interaction. It is believed that indirect
      androgenic activation of paracrine factors like keratinocyte growth factor (KGF)
      in the prostatic stroma influences the growth of epithelial cells. In this study
      we investigated the role androgen plays in stromal cell growth and stimulation of
      KGF in the human prostate. MATERIALS AND METHODS: Stromal cells were derived from
      explant primary culture of human normal or benign prostatic tissue. The effect of
      different dihydrotestosterone (DHT) concentrations on cell proliferation was
      measured using 3[H]thymidine incorporation assay. The effect of DHT on levels of
      KGF protein was determined by Western blotting. The effect of DHT on levels of
      KGF gene expression was measured by various cycles of polymerase-chain-reaction
      (PCR) and multiplex PCR. RESULTS: Characterization of stromal cells showed
      epithelial cells less than 9.5% in all passages. DHT stimulated human prostate
      stromal cells in a dose dependent fashion over a concentration range of 0.001-10
      nM. Immunocytochemical evaluation of KGF after DHT exposure showed a higher
      staining intensity. Relative quantitation of Western blotting showed a 1.93-fold
      increase in KGF protein in the androgen treated stromal cells. At 1 nM DHT
      conventional and multiplex PCR revealed a significant stimulation of the KGF mRNA
      expression. CONCLUSIONS: These data show for the first time that androgen
      stimulates cell proliferation as well as KGF protein and gene expression in human
      prostate stromal cells. This supports the hypothesis that androgen-induced
      stromal-derived KGF stimulates prostate epithelial cell growth.

PMID- 9783974
TI  - Endothelin-1 as a putative modulator of gene expression and cellular physiology
      in cultured human corporal smooth muscle cells.
AB  - PURPOSE: Increases in cytosolic calcium levels trigger smooth muscle contraction
      while nuclear calcium increases are thought to regulate gene expression.
      Endothelin-1 (ET-1) affects both. The goal of these studies was to further
      investigate the importance of ET-1 to corporal physiology by examining its
      actions on proliferation and immediate early gene (IEG) expression in cultured
      human corporal smooth muscle cells. MATERIALS & METHODS: Early passage (1-3)
      smooth muscle cells were grown in culture and exposed to either phenylephrine
      (PE) or ET-1 in the absence and presence of serum, the ET(A) or ET(B) selective
      antagonist BQ123 or IRL1038, or the L-type Ca2+ channel blocker, verapamil. Cell
      proliferation was assessed with a hemocytometer. The effects of ET-1 on c-myc and
      c-fos were evaluated using Northern blot analysis. Parametric or nonparametric
      statistics were used as appropriate. RESULTS: Addition of ET-1 (100 nM) to serum
      starved cultured corporal smooth muscle cells was associated with a nearly 2-fold
      increase in cell number, as well as 2 to 6-fold increases in c-myc and c-fos
      levels. Cellular proliferation was inhibited by ET(A)- or ET(B)-receptor subtype
      blockade with BQ123 (1 microM) or IRL1038 (1 microM), respectively, or blockade
      of Ca2+ channels with verapamil (10 microM). PE (3 microM) had no detectable
      effect on smooth muscle proliferation. CONCLUSIONS: Cell proliferation was
      mediated by activation of the ET(A) and ET(B) receptor subtypes, dependent on
      transmembrane Ca2+ flux, and correlated with significant increases in c-myc and c
      fos mRNA levels. These studies extend previous observations to indicate the
      potential pleotropic actions of this peptide in the regulation of human corporal
      smooth muscle physiology in vivo.

PMID- 9783975
TI  - Effects of atropine, isoproterenol and propranolol on the rabbit bladder
      contraction induced by intra-arterial administration of acetylcholine and ATP.
AB  - INTRODUCTION: In the rabbit, both cholinergic and purinergic nerves mediate
      bladder contraction. Acetylcholine is the neurohumoral transmitter for the
      cholinergic nerves, and ATP is the neurohumoral transmitter for purinergic
      innervation. Beta-adrenergic stimulation mediates relaxation of the bladder. In
      the current study, we investigated the effects of atropine, isoproterenol and
      propranolol on the bladder contraction induced by intra-arterial administration
      of acetylcholine and ATP. METHODS: Mature male New Zealand White rabbits were
      used in this study. A polyethylene catheter with an outer diameter of 0.043
      inches was inserted through the rabbit's right femoral artery until it reached
      the lower abdominal aorta. An 8 F catheter was inserted through the urethral
      orifice into the bladder and secured by tying a 2-0 silk ligature around the
      bladder neck. The catheter was connected to an infusion pump and a pressure
      transducer by a 3-way valve. After 15 ml. of saline was infused into the bladder,
      an intra-arterial administration of acetylcholine and ATP was infused and the
      change of intravesical pressure was quantitated and recorded with a Grass model
      7D polygraph. The procedure was repeated after a 5-minute pretreatment with
      atropine, isoproterenol or propranolol. RESULTS: The results are summarized as
      follows: 1) Baseline intravesical pressure was not altered by pretreatment with
      atropine. Pretreatment with atropine shifted the dose-response curve of
      acetylcholine to the right and the maximal response was reduced by 9%, 49% and
      77% respectively with pretreatment with atropine 10(-8), 10(-7) and 10(-6)
      mole/kg. The dose-response curve of ATP was not significantly affected by
      pretreatment with atropine. 2) Baseline intravesical pressure was lowered by
      pretreatment with isoproterenol. Pretreatment with isoproterenol shifted both
      dose-response curves of acetylcholine and ATP rightward. The maximal response of
      acetylcholine was reduced by 10%, 26% and 37% respectively, and the maximal
      response of ATP was reduced by 6%, 31% and 43% respectively by pretreatment with
      isoproterenol 10(-8), 10(-7) and 10(-6) mole/kg. 3) Baseline intravesical
      pressure was not changed by pretreatment with propranolol. Both dose-response
      curves of acetylcholine and ATP were not significantly affected by pretreatment
      with propranolol. SUMMARY: In conclusion, pretreatment with atropine inhibited
      acetylcholine-induced bladder contraction, but had no effect on ATP-induced
      contraction. Pretreatment with isoproterenol significantly inhibited both
      contractile stimulation by acetylcholine and ATP. Pretreatment with beta
      adrenergic antagonist had no effect on the bladder contraction induced either by
      acetylcholine or by ATP. Thus, although beta-adrenergic stimulation is capable of
      significantly inhibiting the contractile responses to both cholinergic and
      purinergic stimulation, under normal conditions, sympathetic nerves do not
      modulate either cholinergic or purinergic stimulation.

PMID- 9783976
TI  - Muscular urinary sphincter: electrically stimulated myoplasty for functional
      sphincter reconstruction.
AB  - PURPOSE: To reconstruct an electrically stimulated muscular urinary sphincter
      (MUS) using a tailored gracilis muscle free flap with intact nerve. MATERIALS AND
      METHODS: Unilateral surgically tailored gracilis muscle free flaps were
      transferred into the pelvis in eight dogs, leaving the obturator nerve intact.
      The muscle's pedicle vessels were anastomosed to the inferior epigastric artery
      and vein in the pelvis and the muscle was wrapped around the bladder neck.
      Electrodes were inserted into the MUS and connected to a programmable pulse
      generator. After 8 weeks of training the MUS, the pulse generator was programmed
      to be "on" for 4 hours and "off' for 15 minutes in a continuous cycle. Urodynamic
      studies were performed periodically, and at the end of the experiment the MUS and
      proximal urethra were harvested for histology. Three control dogs had sham
      operations. RESULTS: All MUS's functioned well following the procedure. Histology
      of the MUS/urethra complex showed no evidence of stricture. Except for one dog,
      all urethras were easily catheterized. CONCLUSIONS: This electrically stimulated
      innervated free-flap MUS technique effectively increases bladder outlet
      resistance without producing urethral obstruction.

PMID- 9783978
TI  - A new self-expanding lined stent-graft in the dog ureter: radiological, gross,
      histopathological and scanning electron microscopic findings.
AB  - Recurrent or intractable ureteral strictures pose a significant problem for the
      practicing urologist. Metallic stents have been used sparingly for this problem
      with varying success. We investigated the use of a stent-graft consisting of a
      metal stent lined with a porous biocompatible polymer to determine if the liner
      would prevent urothelial ingrowth. One ureter of each of 11 dogs was treated with
      either a metallic woven stent or stent-graft inserted retrograde via a midline
      cystotomy. Six bare wire stents (controls) and five lined with a new, porous,
      biocompatible, polycarbonate elastomer liner (Corethane) were placed. The animals
      were followed radiographically with intravenous urography (IVP) at 6 weeks and
      just prior to sacrifice (12 to 22 weeks). Gross, histological, and electron
      microscopic analyses were performed. The results demonstrate that all of the bare
      metal stented animals developed moderate to severe hydroureteronephrosis with
      significant urothelial hyperplasia and ingrowth through the spaces between the
      metal wires. The animals implanted with lined stents showed one instance of mild
      hydroureteronephrosis (observed radiographically but not grossly at time of
      sacrifice) and virtually no papillary in-growths of urothelium through the stent
      interstices. This obstructive phenomenon was prevented by the porous polymer
      lining. There was no evidence of biodegradation of the liner on scanning electron
      microscopy. Based upon these findings, the marriage of a biocompatible polymer
      which provokes minimal tissue reaction, and metallic stents which provide
      tremendous strength, seems to offer significant advantages when placed into the
      urinary tract to maintain ureteral luminal patency.

PMID- 9783977
TI  - Expression of matrix metalloproteinase-7 and tissue inhibitor of
      metalloproteinase-1 in human prostate.
AB  - PURPOSE: Matrix metalloproteinase-7 (MMP-7), one of the extracellular matrix
      degrading metalloproteinases, plays an important role in carcinoma invasion and
      metastasis. Tissue inhibitor metalloproteinase-1 (TIMP-1), one of the inhibitors
      of MMP-7, regulates extracellular matrix turnover. MATERIALS AND METHODS: Gene
      expression levels of MMP-7 and TIMP-1 were examined in 20 prostate carcinomas
      after hormonal therapy and 12 benign prostate hyperplasias (BPH) by Northern blot
      analysis. Enzymatic activities of MMP-7 were examined in 7 prostate carcinomas
      and 1 BPH in the above prostate tissues by the method of caseinolytic zymography.
      These data were compared with the clinicopathological features. RESULTS: There
      were significant correlations between levels of MMP-7 mRNA or the ratio of MMP-7
      mRNA/TIMP-1 mRNA and pathological stage (p <0.01), lymph node metastasis (p
      <0.05), histological differentiation (p <0.05), vascular invasion (p <0.05), and
      lymphatic invasion (p <0.05). Levels of MMP-7 mRNA and the ratio of MMP-7
      mRNA/TIMP-1 mRNA were significantly increased in prostate carcinomas from
      patients with high levels of serum prostate specific antigen (PSA) (>10 ng./ml.)
      after hormonal therapy (p <0.05). The activation ratio of pro MMP-7 was elevated
      in the cases with advanced prostate carcinoma compared with those of organ
      confined prostate carcinoma and BPH. CONCLUSION: These results suggest that MMP-7
      may play an important role for invasion and metastasis in prostate carcinomas,
      and the balance between MMP-7 and TIMP-1 expression may relate to an invasive
      ability of prostate carcinomas.

PMID- 9783979
TI  - Absence of expression of transforming growth factor-beta type II receptor is
      associated with an aggressive growth pattern in a murine renal carcinoma cell
      line, Renca.
AB  - Transforming growth factor-beta1 (TGF-beta1) inhibits the proliferation of many
      cancer cells. However, tumor cells frequently become resistant to this inhibitory
      effect due to the absence of TGF-beta receptor (TbetaR) expression. This study
      reports the nature of TGF-beta sensitivity in an aggressive murine renal
      carcinoma cell line, Renca, investigated in a series of experiments. The growth
      of Renca cells, in tissue culture, was not sensitive to the inhibitory effect of
      TGF-beta1 with doses ranging from 0.1 to 10 ng./ml., nor was this cell line
      sensitive to the effect of TGF-beta1 in inducing the expression of plasminogen
      activator inhibitor-I. Renca cells expressed TGF-beta1 mRNA and protein, as
      determined by RT-PCR and ELISA, respectively. The level of TGF-beta1 production
      by Renca cells was moderate, thus eliminating the possibility that endogenous TGF
      beta1 production might be masking the effect of TGF-beta sensitivity.
      Furthermore, Renca cells expressed TbetaR-I mRNA, but did not express TbetaR-II
      mRNA, suggesting that the absence of this receptor may be the cause of TGF-beta
      insensitivity. Additionally, a vector containing the TbetaR-II cDNA was
      transiently transfected into Renca cells. The inhibitory effect of TGF-beta1 was
      introduced in Renca cells after transfection with this receptor. At the same
      time, the growth rate of these cells diminished significantly when compared with
      that of the wild type Renca cells, as judged by the rate of [3H]-thymidine
      incorporation in the absence of any exogenous TGF-beta1. These observations
      demonstrated that Renca cells lack the functional TbetaR-II and suggest that
      their aggressive growth pattern is due, at least in part, to their insensitivity
      to TGF-beta.

PMID- 9783980
TI  - Altered gamma-catenin expression correlates with poor survival in patients with
      bladder cancer.
AB  - PURPOSE: We studied the expression of alpha-, beta-, gamma- catenin and E
      cadherin in transitional cell carcinoma (TCC) and normal bladder epithelium and
      correlated these results with pathological and clinical parameters. MATERIALS AND
      METHODS: We used an avidin-biotin immunoperoxidase technique to examine the
      cellular localization of alpha-catenin, beta-catenin, gamma-catenin and E
      cadherin in 68 TCC and 14 normal bladder biopsies. RESULTS: E-cadherin, alpha
      catenin, beta-catenin and gamma-catenin were expressed in a normal membranous
      pattern in all normal bladder epithelium specimens. Loss of normal surface E
      cadherin, alpha-catenin, beta-catenin and gamma-catenin expression was found in
      52/68 (76.4%) tumors, 57/68 (83.8%) tumors, 54/68 (79.4%) tumors and 54/68
      (79.4%) tumors (p <0.001). There was a significant correlation between the loss
      of normal membranous expression of catenins and E-cadherin and increased grade (p
      <0.05). A highly significant correlation was observed between the loss of
      expression of E-cadherin, alpha-catenin and gamma-catenin, but not beta-catenin,
      with increased TNM stage (p <0.05). The abnormal expression of gamma-catenin as
      well as E-cadherin was correlated with poor survival (p <0.05). CONCLUSIONS: E
      cadherin-gamma-catenin complex may be a useful prognostic marker in bladder
      cancer. Work is in progress to establish whether normal membranous catenin
      expression can be enhanced by gene transfer or biological therapy to induce a
      less invasive and metastatic phenotype.

PMID- 9783981
TI  - Alteration of Sertoli cell differentiation in the presence of carcinoma in situ
      in human testes.
AB  - PURPOSE: We investigated Sertoli cells in testicular biopsies with carcinoma in
      situ (CIS) in respect to cytokeratin expression to elucidate the status of
      Sertoli cell differentiation adjacent to CIS in human testes. Cytokeratin 18
      intermediate filaments indicate a state of undifferentiation usually observed in
      Sertoli cells of prepubertal testes. MATERIALS AND METHODS: 29 testicular
      biopsies presenting CIS were investigated by means of immunohistochemistry, using
      a polyclonal antibody against placental-alkaline phosphatase to detect CIS cells
      and a monoclonal antibody against human cytokeratin 18 to show expression of
      cytokeratin 18 intermediate filaments in Sertoli cells. RESULTS: All tubules
      bearing CIS showed positive cytokeratin expression of Sertoli cells if tubules
      were devoid of normal germ cells. However, a total of 13 specimen revealed CIS
      cells together with normal germ cells. In the presence of CIS cells together with
      round or elongated spermatids, adjacent Sertoli cells did not express cytokeratin
      immunoreactivity. In the case of combined presence of CIS and spermatogonia and
      primary spermatocytes, Sertoli cells could be found either immunopositive or
      immunonegative, and were positive in tubules with CIS and spermatogonia only.
      CONCLUSIONS: Sertoli cells associated with CIS cells undergo a process of
      dedifferentiation, seen by the re-expression of cytokeratin intermediate
      filaments. We suggest that this dedifferentiation results in a loss of Sertoli
      cell function and leads to a cessation of spermatogenic activity.

PMID- 9783982
TI  - Growth hormone enhances regeneration of nitric oxide synthase-containing penile
      nerves after cavernous nerve neurotomy in rats.
AB  - PURPOSE: As growth hormone has been reported to improve nerve regeneration, we
      studied the effect of rat growth hormone (GH) on the regeneration of nitric oxide
      synthase (NOS)-containing penile nerves and the neurons in the pelvic ganglia
      after unilateral cavernous nerve neurotomy in rats. MATERIALS AND METHODS: Male
      rats were divided into three groups: sham operation (n = 14); unilateral
      neurotomy of a 5 mm. segment of the cavernous nerve (n = 14) with subsequent
      injection of buffer solution only; and unilateral neurotomy with GH injection (n
      = 14). Electrostimulation of the intact cavernous nerve was performed at 1 and 3
      months. Nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining
      was used to identify NOS in penile nerve fibers of the mid-shaft segment and in
      neurons of the pelvic ganglia. RESULTS: One month after unilateral neurotomy,
      both the buffer alone and GH-treated groups showed a significant decrease in NOS
      containing nerve fibers in the dorsal and intracavernosal nerves on the side of
      neurotomy. At 3 months, the number of NOS-containing nerve fibers in the buffer
      alone group did not increase, while the GH-treated group showed a significant
      increase. In the GH-treated group at 3 months, more NOS-positive neurons in the
      pelvic ganglia were found on the intact side than on the side of neurotomy (p
      <0.034), indicating that the regeneration derives from pelvic ganglion neurons on
      the intact side. Furthermore, electrostimulation in the GH-treated group revealed
      a greater maximal intracavernosal pressure and a shorter latency period at 3
      months than in those given buffer alone. CONCLUSIONS: Our results show that GH
      injection significantly enhances the regeneration of NOS-containing fibers in the
      dorsal and intracavernosal nerves after unilateral cavernous nerve injury. We
      believe that GH administration may present a new and more physiologic approach to
      the treatment of erectile dysfunction after radical pelvic surgery.

PMID- 9783984
TI  - Antibacterial activity of antibiotic coated silicone grafts.
AB  - PURPOSE: Postoperative infection remains one of the most serious complications of
      implantation of penile prostheses. Attempts to reduce the rate of infection by
      spraying the prosthesis with an antibiotic solution prior to implantation, along
      with perioperative antibiotics, have failed to eradicate infection. No published
      studies have evaluated the effect of antibiotic coating of penile prostheses. In
      this study, we evaluate the antibacterial effect of antibiotic-coated silicone
      strips as a surrogate for the penile prosthesis. MATERIALS AND METHODS: Strips
      coated with several different antibiotics were dipped in bacterial solutions
      containing Staphylococcus epidermidis or S. aureus and implanted subcutaneously
      in adult Sprague-Dawley rats. After a week, the strips were removed, and the
      number of bacteria on the strips and in the surrounding tissue were determined.
      The in vitro antibiotic activity of the antibiotic-coated strips against the same
      organisms was also determined. RESULTS: In the group of rats that received
      silicone strips contaminated in vitro with S. epidermidis, six of nine control
      rats yielded strips and tissues containing heavy bacterial growth. None of six
      strips coated with rifampin/minocycline yielded bacterial growth, nor did any of
      the seven strips coated with vancomycin. One of seven rats that received amikacin
      coated strips had infection of the strip. The tissue results were similar to the
      strip results. In the group using S. aureus as the contaminating bacterium, the
      strips and tissues from eight of nine control rats yielded bacteria. None of the
      six rifampin/minocycline-coated strips yielded bacteria, while two of seven
      vancomycin-treated strips and two of six amikacin-coated strips were infected
      with S. aureus. The difference in bacterial growth between controls and
      antibiotic-coated strips reached a level of statistical significance for the
      rifampin/minocycline and vancomycin groups and was highly significant for the
      rifampin/minocycline groups. CONCLUSION: The experimental results presented here
      suggest that coating silicone graft material with antibiotics, particularly
      rifampin/minocycline, can reduce the incidence of graft colonization in
      contaminated wounds in rats, even in the absence of systemic antibiotics. These
      graft materials may prove useful in preventing the infection of penile
      prostheses.

PMID- 9783983
TI  - Prostate specific origin of dipeptidylpeptidase IV (CD-26) in human seminal
      plasma.
AB  - PURPOSE: A number of peptidases which can metabolize certain bioactive peptides
      and growth factors have been identified in seminal plasma. Our goal in this study
      was to determine molecular properties and the tissue source(s) for one of these
      peptidases, dipeptidylpeptidase IV (DPP IV), in human seminal plasma. MATERIALS
      AND METHODS: We measured the activities of DPP IV with the dipeptide glycylprolyl
      p-nitroanalide and its molecular forms using immunoblotting of seminal plasmas of
      men who were vasectomized or with different sperm concentrations, and in
      prostatic and seminal vesicle secretions of men undergoing prostatic surgery.
      RESULTS: DPP IV in seminal plasma of vasectomized men was a membrane associated
      dimer comprised of subunits of approximately 110 kDa. Its activity did not differ
      in seminal plasmas of vasectomized, azoospermic, oligozoospermic and
      normozoospermic men indicating no correlation with the concentration of sperm
      originally present in the semen. The DPP IV antigen (CD -26) and enzymic activity
      were present in prostatic secretion, but absent from that of the seminal
      vesicles. These data indicate that the prostate gland is the primary source of
      DPP IV activity in seminal plasma. There was little variation in its activities
      in repeat seminal plasma samples from the same individual, and there was no
      change in its activity with age to 50 years. CONCLUSIONS: DPP IV in seminal
      plasma was derived from the prostate gland and it may be useful as a bioindicator
      of prostate function and/or disease with age in men.

PMID- 9783985
TI  - Expression of metalloproteinase 2 and 9 and their inhibitors in renal cell
      carcinoma.
AB  - Degradation of the extracellular matrix is necessary for invasion and metastasis
      by cancer cells. Two gelatinolytic matrix metalloproteinase enzymes, MMP-2 and
      MMP-9, are supposed to be key enzymes in this process. The purpose of this study
      was to correlate the presence of MMP-2, MMP-9 and their inhibitors with the
      tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2 RNA using reverse
      transcriptase PCR technique with tumor stage in 17 samples of renal cell
      carcinoma. The ratio of tissues expressing MMP-2 and MMP-9 to those expressing
      TIMP-1 and TIMP-2 was defined to be 1 in normal kidney tissue. This MMP:TIMP
      ratio was significantly increased to 2.43 (standard deviation, SD = 0.8) in
      locally confined renal cell carcinoma and to 4.86 (SD = 1.1) in advanced
      carcinoma (p <0.01). In primary tumor cell lines the ratio of MMP:TIMP expression
      was 3.44 (SD = 0.6). These data suggest that the balance of MMP-2 and MMP-9 to
      TIMP-1 and TIMP-2 expression is an essential factor in the aggressiveness of
      renal cell carcinoma.

PMID- 9783986
TI  - Role of autonomic innervation in rat prostatic structure maintenance: a
      morphometric analysis.
AB  - PURPOSE: To analyze the effects of major pelvic ganglion (MPG) excision on the
      structure of rat prostate. MATERIALS AND METHODS: We studied 80 Sprague-Dawley
      rats (300-350 gm. weight). Forty-two were anesthetized and the right MPG excised.
      After 28-30 days, the same-side prostatic ventral lobe (VL) was obtained for
      macroscopic, light (LM), and transmission electron microscopy (TEM) evaluation. A
      computerized morphometric analysis was performed on epithelial and muscle cells.
      Results were compared with 38 right VL of non-operated, same-aged rats. RESULTS:
      A 36.6% reduction (0.14 gm.) of VL fresh weight was found in the denervated group
      (p <0.001). Mean tissue proportions observed in the LM study were 27.9%
      (epithelial), 48.3% (stromal), and 51.8% (glandular) in the non-operated group,
      versus 14.8% (p <0.001), 55.7%, and 44.4% (not significant) respectively, after
      MPG excision. No difference was found regarding the vascular pattern. In the
      denervated rats, TEM analysis found a significant reduction in total and
      supranuclear cell height (change in cell polarity), as well as in cytoplasm,
      Golgi and endoplasmic reticulum areas. Secretory granule count, total area (p
      <0.001), and density of apical microvilli were also reduced. On the other hand,
      only an increase in the area of cytoplasm ribosomal aggregates was detected in
      the smooth muscle cell analysis. CONCLUSIONS: Our study demonstrated a rat
      prostatic VL atrophy in the denervated side, due to a shrinkage in the epithelial
      component of the gland. Ultrastructural findings also suggest an overall decrease
      of epithelial cell secretory activity. Finally, the increase of ribosomal
      aggregates found in stromal smooth muscle could reflect an activation of these
      cells after denervation.

PMID- 9783987
TI  - In vitro passive sensitization of the ureter as a basis for the study of
      noninfectious ureteral inflammation.
AB  - PURPOSE: To develop an in vitro model of passive sensitization for the ureter for
      the study of noninfectious ureteral inflammation. MATERIALS AND METHODS: Human
      ureteral tissues were obtained from excess segments of ureters from patients
      undergoing donor nephrectomy. Following excision, ureters were placed in
      physiologic salt solution (PSS) and passively sensitized by incubating with
      ragweed serum from allergic donor (1 ml. serum: 4 ml. PSS) for 20 hours at room
      temperature. Ureteral segments were incubated with PSS only and served as non
      sensitized controls (n = 4). After sensitization, excess serum was removed by
      serial washing with PSS without serum. Ureteral strips were then suspended in
      vitro for determination of tissue contraction. Contractile responses and
      histamine release were measured. Tissues were then exposed to antigen. To
      investigate the role of inflammatory mediators in tissue contraction, 4 groups of
      8 sensitized ureteral segments were incubated for 1 hour with the following
      substances: a H1 histamine receptor antagonist (pyrilamine), an inhibitor of
      prostaglandin synthesis (indomethacin), an inhibitor of leukotriene synthesis (A
      64077), and a control substance (DMSO). Following incubation, the tissues were
      exposed to antigen, and contraction and histamine release were determined.
      RESULTS: Sensitized ureteral segments (n = 8) responded to antigen with
      contraction (30% BaCl maximum; p <0.01) and histamine release (205/ng./gm.
      tissue) within the first 5 minutes of superfusion. Non-sensitized control
      segments (n = 4) did not respond. Both indomethacin and pyrilamine reduced (7-10%
      of BaCl maximum; p <0.05) the contractile response of sensitized ureter to
      antigen, whereas A-64077 did not. Analysis of the superfusate for histamine
      indicates that indomethacin reduced histamine release (150 ng./gm.) whereas A
      64077 and pyrilamine did not (p <0.05). CONCLUSION: We have demonstrated that
      ureteral segments can be passively sensitized and that subsequent antigen
      challenge stimulates contraction and histamine release. Our findings suggest that
      contraction of ureteral tissue and histamine release may be utilized as an
      inherent bioassay indicating the activity of inflammatory mediators. In addition,
      these results suggest that both prostaglandins and histamine, but apparently not
      leukotrienes, participate in the early inflammatory response to antigen challenge
      of the sensitized ureter.

PMID- 9783989
TI  - Effectiveness of extracorporeal shockwave lithotripsy in the management of stone
      bearing horseshoe kidneys.

PMID- 9783988
TI  - Vascular endothelial growth factor is a predictor of relapse and stage
      progression in superficial bladder cancer.

PMID- 9783990
TI  - Effects of SWL on glomerular filtration rate and renal plasma flow in
      uninephrectomized minipigs.

PMID- 9783991
TI  - The use of milk progesterone profiles to characterise components of subfertility
      in milked dairy cows.
AB  - Milk progesterone (P4) concentrations of 1682 postpartum (PP) dairy cows during
      2503 lactations were used to define and quantify the incidence of atypical
      ovarian patterns and to assess their impact on reproductive performance. A total
      of 257 animals (10.94%) with their first significant luteal activity after day 44
      PP were considered a result of delayed ovulation type I (DOVI). Prolonged luteal
      activity (P4 > 3 ng/ml for at least 19 days) observed in 170 (7.3%) and 161
      (6.35%) animals during first and subsequent cycles was considered a result of the
      presence of a persistent corpus luteum (CL), respectively denoted as PCLI and
      PCLII. Following the demise of an oestrous cycle CL, a total of 322 (12.85%)
      animals showed a delayed ovulation Type II (DOVII) with P4 < 3 ng/ml for > 12
      days. In 238 inseminated animals (9.92%) prolonged luteal activity was followed
      by the CL demise which may indirectly indicate the incidence of a late embryo to
      early foetal mortality (LEM). In this study animals during 794 (31.7%) lactations
      had at least one atypical ovarian pattern before insemination that, in comparison
      to those with typical P4 patterns, contributed to a delayed conception (88.2 vs.
      106.2 days), higher number of services per conception (1.49 vs. 1.8), lower first
      service conception rate (60.9 vs. 43.7%) and a reduced total conception rate
      (92.6 vs. 82.1%), all of which were significantly different at P < 0.001. The
      incidence of PCLI and PCLII before insemination resulted in a higher level of
      LEM. Milk progesterone monitoring offers an accurate and objective measurement of
      factors associated with PP ovarian activity which will assist in investigating
      the genetic and environmental factors' affecting fertility.

PMID- 9783992
TI  - Effect of timing of oestradiol benzoate injection relative to gonadotropin
      treatment on superovulatory response, and on embryo yield and quality in beef
      heifers.
AB  - Variation in superovulatory responses in cattle may be related to the stage of
      follicular growth at the time of gonadotropin treatment. Waves of follicle growth
      are regulated by both follicle-stimulating hormone (FSH) and oestradiol. The
      objective of experiment 1 was to determine the dynamics of follicle wave
      emergence and the relationship with FSH and oestradiol concentrations, after
      treatment of heifers with oestradiol benzoate (ODB) in the presence of an
      intravaginal progesterone-releasing device (CIDR-B). Experiment 2 examined the
      superovulatory response, embryo yield and quality following treatment with
      porcine follicle-stimulating hormone (pFSH) at different times relative to ODB
      injection. In experiment 1, 28 beef heifers were treated with a CIDR for 9 days
      and allocated at random to one of four groups to receive either: (I) CIDR only,
      or 5 mg ODB given as a single intramuscular injection at (II) day 0 (d0); (III)
      day 1.5 (d1.5); or (IV) day 3 (d3) post CIDR insertion. Ovaries were examined
      using daily ultrasound and blood samples were collected twice daily for 11 days.
      In experiment 2, 96 heifers were treated with a CIDR and 5 mg ODB as in
      experiment 1, and were allocated using a 4 x 3 factorial design plan to a
      superovulation programme using three doses (400 IU; 600 IU; 800 IU) of pFSH. FSH
      was given for 4 days at 12-h intervals beginning 6.5 days after CIDR insertion.
      Heifers received prostaglandin analogue 12 h before CIDR removal and were
      inseminated (AI) at 48 and 60 h post CIDR withdrawal and embryos were recovered 7
      days after AI. In experiment 1, the interval from CIDR insertion to follicle wave
      emergence (FWE) was longer (P < 0.05) in heifers treated with ODB at d1.5 (5.4 +/
      0.4 days) and d3 (5.1 +/- 0.6 days) compared to heifers treated with CIDR only
      (2.4 +/- 0.4 days). On the basis of time to proposed injection of pFSH heifers
      would have had follicle emergence 4.4, 2.3, 1.5 and 1.4 days prior to pFSH for
      groups I, II, III and IV, respectively. In experiment 2, heifers treated with ODB
      at d1.5 had a higher (P < 0.05) superovulatory response (18.2 +/- 1.7) than
      heifers treated at d3 (12.8 +/- 1.7), but superovulatory response in both groups
      did not differ (P > 0.05) from heifers treated at d0 (14.4 +/- 2.0) or with CIDR
      only (15.0 +/- 1.8). There were fewer (P < 0.05) freezable-grade embryos
      recovered from heifers treated with ODB at d0 (1.5 +/- 0.7) and d3 (2.1 +/- 0.5)
      compared to heifers treated at d1.5 (3.0 +/- 0.6) or in heifers treated with CIDR
      only (3.4 +/- 0.7). Increasing the dose of pFSH caused a linear increase in the
      superovulatory response (11.7 +/- 1.0, 15.8 +/- 1.4 and 18.0 +/- 1.9) and in the
      number of embryos recovered (5.8 +/- 0.9, 7.0 +/- 0.8 and 9.1 +/- 1.0) for 400
      IU, 600 IU and 800 IU, respectively. In conclusion, heifers treated with ODB had
      wide variation in time to follicle wave emergence and there was not a consistent
      beneficial effect of pretreatment with ODB on embryo yield and quality following
      superovulation.

PMID- 9783993
TI  - Effects of the presence of rams during pregnancy on lambing performance in ewes.
AB  - Ewes of the Prealpes-du-Sud breed (n = 112) were mated with fertile rams and were
      used to investigate the effect of the presence of vasectomized rams during
      pregnancy on reproductive outcomes. Ewes in the control group (n = 56) were
      isolated from rams during the whole period of pregnancy, whereas those in the
      experimental group (n = 56) were kept with vasectomized rams from day 10 post
      mating until lambing. At day 10 post-mating, a series of blood samples was
      collected every 15 min for 8 h from five control ewes and five experimental ewes
      to determine their patterns of LH secretion. The introduction of the ram was
      associated with a rapid increase of pulsatile LH release. The lag between the
      introduction of the ram and the onset of the first episodic LH release was less
      than 15 min. The mean(+/- sem) number of LH pulses/4 h after the introduction of
      the ram (2.8 +/- 0.4) was significantly higher (P < 0.01) than that observed/4 h
      before the introduction of the ram (1.4 +/- 0.2). Although more ewes were
      pregnant in the control group (87.5%) than in the ram-exposed group (82.1%), the
      difference was not significant. The presence of rams did not affect gestation
      length (145.8 days), overall lamb mortality (3.5%) or birth weights of single
      (3.96 kg), twin (3.24 kg) or triplet (2.59 kg) lambs. The proportion of ewes with
      multiple births in the control group (69.4%) was significantly greater (P < 0.05)
      than that in the ram-exposed ewes (47.8%). The ewes in the control group had
      significantly more (P < 0.01) twin lambs born alive (72.3%) than the ewes in the
      ram-exposed group (50.0%). In conclusion, the presence of vasectomized rams
      during early pregnancy affected the incidence of multiple births but did not
      affect pregnancy rate or gestation length. The altered fertility of ewes exposed
      to vasectomized rams may reflect changes in embryonic loss during early
      pregnancy.

PMID- 9783994
TI  - Development of a nutritional strategy for increasing lamb survival in Merino ewes
      mated in late spring/early summer.
AB  - A nutritional strategy for increasing lamb survival in Merino ewes mated in late
      spring/early summer was evaluated in a commercial flock over two consecutive
      years (Year 1, n = 680; Year 2, n = 325). The strategy combined the 'ram effect'
      to synchronise oestrus and hence parturition, plus supplementary feeding of lupin
      grain for 14 days in the expected early post-parturient period. Supplementary
      lupin feeding commenced 12 days after the expected start of lambing. Lambing was
      highly synchronised over a 14-day period commencing 17-19 days after the expected
      start of lambing, in both years. Supplementary feeding did not affect lamb
      birthweight in either year but subsequent increases in weight were observed at
      weaning in Year 1 (1.4 kg; P = 0.06) and tail docking in Year 2 (1.3 kg; P <
      0.05). Lamb survival was increased by 7 lambs per 100 ewes exposed to rams in
      both years. (Year 1 at weaning, NS; Year 2 at tail docking, P < 0.001). It was
      concluded that the strategy improved both lamb survival and lamb performance
      possibly due to an effect of lupin supplementation on colostrum and subsequent
      milk production.

PMID- 9783995
TI  - Effects of post-ovulatory food deprivation on oviductal sperm concentration,
      embryo development and hormonal profiles in the pig.
AB  - Nutrition is one of the multiple factors that modulate reproduction in animals.
      The effect of 48 h food deprivation on reproductive and metabolic hormonal
      changes in relation to cleavage rates was studied. Insemination of 15 sows was
      performed 20-10 h prior to expected ovulation and ova were recovered at slaughter
      65-91 h post ovulation. Blood samples were collected every second hour, beginning
      from the time of insemination until slaughter, for measurements of progesterone,
      cortisol, the prostaglandin F2alpha metabolite (15-keto-13,14-dihydro-PGF2alpha)
      and insulin levels. The embryos from the food-deprived sows (D-group) had fewer
      accessory spermatozoa in their zona pellucida (ZP) compared with the control sows
      (C-group). A lower cleavage rate of the embryos in the D-group compared with the
      C-group was detected. Plasma progesterone, cortisol and prostaglandin F2alpha
      metabolite levels were significantly higher in the D-group compared with the C
      group. Food deprivation is associated with changes in reproductive and metabolic
      hormones that might lead to changes in the oviductal environment, culminating in
      a lower cleavage rate of the embryos and presence of fewer viable spermatozoa in
      the reservoir.

PMID- 9783996
TI  - Evaluation of reproductive failure of female pigs based on slaughterhouse
      material and herd record survey.
AB  - Reproductive organs were collected from one slaughterhouse and culling data were
      obtained from Finnish swine herd records to determine the types and frequencies
      of various fertility disturbances in Finnish female pigs. Detailed information
      about the type and occurrence of fertility disturbances was obtained through a
      close examination of the slaughterhouse material. A total of 1708 reproductive
      organs of female pigs were examined. The following findings were recorded: no
      macroscopical abnormalities 52.3%, inactive ovaries 25.1%, parovarian cysts
      22.9%, single ovarian cysts 3.1%, multiple ovarian cysts 3.1%, uterine disorders
      1.4%, ovarian adhesions 1.1%, congenital anomalies 0.8%, tumour-like lesions in
      ovaries 0.8%, obstruction of oviduct 0.2%, and suppurative ovarian infection
      0.1%. A large proportion, 42% of the culled gilts and 39% of the culled sows,
      were slaughtered because of impaired fertility based on no pregnancy, no heat or
      poor piglet production. The sows were removed from the herds 33 days on average
      after weaning.

PMID- 9783997
TI  - Effect of passive immunization with buffalo follicular fluid antisera on ovarian
      activity in guinea pigs.
AB  - Ovarian activity and follicular populations were studied in guinea pigs (Cavia
      porcellus) following administration of antisera against buffalo follicular fluid
      (buFF). Antibodies were raised in rabbits and the titre tested by immunodiffusion
      assay. Fourteen guinea pigs cycling normally were randomized into two groups.
      Animals in Group I (n = 8) were treated (i.p.) with 0.5 ml antisera and in Group
      II (control, n = 6) with the same volume of normal rabbit serum at 12 h intervals
      on the 10th and 11th day of their oestrous cycle. They were sacrificed 24 h after
      onset of estrus when ovulation points were counted and ovaries processed for
      microscopical examination. Treatment with buFF-antisera increased ovulation rate
      (3.6 vs. 2.0; p < 0.01) but had no significant effect on the total number of
      follicles. However, the treatment reduced the percentages of atretic follicles in
      all size classes. These results indicated that the administration of a buFF
      antisera produced in the rabbits increased ovulation rate in guinea pigs by
      reducing the incidence of atresia.

PMID- 9783998
TI  - A brief history of the use of laboratory animals for the prediction of
      carcinogenic risk for man with a note on needs for the future.
AB  - This review discusses developments during the last 60 years in the field of
      carcinogenicity testing based on the use of laboratory animals. Improvements that
      have occurred in the quality of animals and in the way in which tests are
      conducted are considered, along with the importance of distinguishing between
      fatal and incidental tumours. Still to be faced is a need to control calorie
      intake in the course of carcinogenicity testing. A necessity for a better
      understanding of how disturbances of physiological and/or hormonal status can
      predispose to tumour development and for more comparative metabolism studies is
      stressed. Recognition of the fact that thresholds exist for carcinogenesis by non
      genotoxic compounds poses a need for avoiding unrealistically high levels of
      exposure and for more and better information on how different species metabolise
      test agents.

PMID- 9783999
TI  - Spongiform neuropathy induced in dogs by prolonged, low-level administration of 6
      aminonicotinamide (6-ANA).
AB  - The objective of this study was to demonstrate the effects of prolonged exposure
      to 6-ANA at low dose-levels in dogs. A male and a female Beagle dog received
      daily oral repetitive doses of 1 mg/kg or less for 20 weeks. Both dogs showed
      lacrimation, conjunctivitis, reduced motility and anemia since the second week of
      treatment. The female dog was more affected than the male and at the end of
      treatment period it had tremor, hanging lower jaw, stepping gait of the hind
      limbs, hunched posture, and general debilitation. Post-mortem examination of the
      female dog revealed prominent brain edema with pressure atrophy of the dorsal
      cranial bones. Microscopic examination of the nervous system revealed spongiform
      neuropathy in both animals mainly affecting the telencephalic cortex and
      hippocampal fascia dentata, the substantia gelatinosa in the spinal cord and the
      dorsal root and autonomic ganglia. The changes were produced by vacuolation of
      astrocytes in the central nervous system and perineuronal satellite cells in the
      ganglia. Examination of the other organs revealed thymic atrophy and high
      hematopoietic activity of the bone marrow in both dogs. The male had severe
      interstitial edema and vacuolar degeneration of the testicular seminiferous
      tubules and the female had marked chronic pyelonephritis. This chemically induced
      spongiform neuropathy in dogs obviously represents a subchronic form of the
      "energy deprivation syndrome" induced by impaired glucose utilization. Vacuolar
      degeneration of the testicular seminiferous epithelium may have the same
      pathogenesis.

PMID- 9784000
TI  - Patterns of drug-induced cardiovascular pathology in the beagle dog: relevance
      for humans.
AB  - In toxicity studies, the examination of tissue sections for pathological changes
      is the principle method for the identification of organ toxicity and
      characterisation of the hazard of novel drugs for humans. Study of the patterns
      of pathological alterations also represents an important means of developing an
      understanding of the mechanism of toxicity. However as pathological change
      frequently represents a final common expression of diverse processes, additional
      functional information is often required for a clear understanding of the
      mechanisms of toxicity. This is exemplified in the evaluation of the effects of
      drugs on the beagle dog cardiovascular system where an understanding of
      mechanisms is crucial in the assessment of human risk. Particular patterns of
      drug-induced structural change in the myocardium or blood vessels are frequently
      linked to specific mechanisms of toxicity. However, assessment based on the
      interpretation of patterns of cardiovascular pathology alone may be misleading.
      Quite different changes in cardiac and vascular function or direct cellular
      toxicity may also be manifest by pathological features in common. Therefore, a
      clear understanding of mechanism frequently requires additional in vivo or in
      vitro physiological, pharmacological, biochemical or other mechanistic
      information. The beagle dog remains an important model for the study of
      cardiovascular toxicity because in this species, haemodynamic changes and
      pathological alterations can be related in a way that provides the basis for the
      safe study in humans of novel drugs with cardiovascular activity.

PMID- 9784001
TI  - Cardiovascular function and brain metabolites in normal weight and intrauterine
      growth restricted newborn piglets--effect of mild hypoxia.
AB  - In order to clarify the influence of intrauterine growth restriction on systemic
      hemodynamics, catecholamine response, and regional distribution of brain energy
      metabolites per se and during mild hypoxic episodes a study was performed in
      thirty newborns with a well-characterized state of intrauterine and intra-natal
      development. Thirty animals were divided into fifteen normal weight piglets (NW)
      and fifteen intrauterine growth restricted (IUGR) piglets according to their
      birth weight. Category "NW" covered animals with a birth weight of > 40th
      percentile; IUGR category covered animals with a birth weight of > 5th and < 10th
      percentiles. Animals were anesthetized with halothane in 70% nitrous oxide and
      30% oxygen and after immobilization artificially ventilated. The acid-base
      balance and blood gas values at baseline conditions were similar within the
      different groups investigated and consistent with other data obtained from
      anesthetized and artificially ventilated newborn piglets. Mild hypoxic hypoxia
      which was induced by lowering the FiO2 from 0.35 to 0.15 resulted in reduced
      arterial pO2 (NW: from 115 +/- 37 mmHg to 39 +/- 7 mmHg; IUGR: from 117 +/- 23
      mmHg to 39 +/- 3 mmHg; p < 0.05), but arterial pH and pCO2 remained unchanged.
      Under baseline conditions arterial blood pressure, cardiac output, and myocardial
      contractility, expressed as dp/dt(max) and plasma catecholamine values were
      similar in all groups studied. Heart rate was slightly increased in IUGR (p <
      0.05). Mild hypoxia led to a strong increase of myocardial contractility in NW as
      well as IUGR piglets to 2.4 and 2.7 fold and remained increased during recovery
      (p < 0.05). Moreover, total peripheral resistance was enhanced at the end of
      recovery period in IUGR animals (p < 0.05). There was a significant increase of
      epinephrine (E) in NW animals in comparison to sham-operated animals (p < 0.05).
      Interestingly, during reoxygenation the further increase in E and norepinephrine
      (NE) levels were enhanced in the animals which suffered from mild hypoxia (p <
      0.05). Regional distribution of brain tissue metabolites was partly affected by
      intrauterine growth restriction. In particular, brain tissue glucose content was
      strongly reduced by 65 to 72 per cent in all brain regions investigated. Mild
      hypoxia led to an increase of about 30 percent in NW animals (p < 0.05). In IUGR
      piglets the percentage increase of brain glucose content was on an average more
      pronounced but with considerably higher variance. Also, a strong increase of
      brain lactate content appeared here (p < 0.05). In contrast, brain tissue ATP was
      quite similar in all groups studied, but brain creatine phosphate was
      significantly reduced in some forebrain structures of IUGR piglets after mild
      hypoxia (figure 2, p < 0.05). In summary, this investigation provides information
      on cardiovascular functions and brain metabolites of normal weight and naturally
      occurring growth restricted newborn piglets. Mild hypoxemia was well-tolerated
      from both animal groups. It is suggested that lactate may play a significant role
      as a source for brain energy production in the newborn IUGR piglets.

PMID- 9784002
TI  - Ciprofibrate--racemate and enantiomers: effects of a four-week treatment on male
      inbred Fischer rats. A biochemical and morphological study.
AB  - Ciprofibrates (racemate and both enantiomers, Raccip, R- and Scip) were
      administered orally in doses of 1 and 10 mg/kg once daily over 28 days to male
      inbred Fischer 344 rats, age 90-110 days at the beginning of the experiment. Body
      mass gain was observed in all groups. The 1 mg groups showed almost no difference
      to the control group. The 10 mg groups exhibited less body mass gain, most
      pronounced in the Scip group. Liver masses were increased in a dose dependent
      manner up to more than 200%, only the 10 mg Scip group was not significantly
      different from the 1 mg group which exhibited an increase in liver weight to
      about 175%. Also the kidney weights increased to 130%, whereas thymus and spleen
      weights were decreased in the high dose groups. Liver microsomal cytochromes P450
      (P450) concentrations were not altered in the 1 mg groups and distinctly lowered
      in the 10 mg groups. Ethoxyresorufin and ethoxycoumarin O-deethylations were
      lowered in all experimental groups in a dose dependent manner, after
      administration of the high doses down to 30% of the control levels or less.
      Pentoxyresorufin O-depentylation, however, was increased in all 1 mg groups. In
      the high dose groups it was not altered. Ethylmorphine N-demethylation was
      decreased after administration of the high doses by about 50%, but only Scip
      decreased this reaction also after administration of the low dose. NADPH/Fe2+
      stimulated microsomal luminol and lucigenin amplified chemiluminescence was
      increased, whereas hydrogen peroxide formation was depressed even by the low
      doses to 50% of the normal values, to about 25% by the high doses. Microsomal
      lipid peroxidation, however, was only slightly or not influenced. Glutathion
      concentrations (in the reduced and the oxidized form) were increased in a dose
      dependent manner by about 20 to 30%, the concentration of lipid peroxides was not
      significantly influenced. Thus, the effects of the enantiomers were not different
      and were similar to those of the racemate. In serum, cholesterol and
      triglycerides were only moderately lowered. Albumin concentrations were
      significantly enhanced in all groups, total proteins after 1 mg/kg Raccip only.
      Serum bilirubins were not altered, and among the indicator enzymes for liver
      damage only ALAT, alkaline phosphatase and the dehydrogenases were increased, in
      no case higher than twofold. Histologically distinct effects were seen after
      administration of both doses, more pronounced after 10 mg/kg, but with no
      differences between the enantiomers and Raccip: marked hypertrophy of the
      hepatocytes, reduced staining of the nuclei, strongly acidophilic granulated
      cytoplama, no basophilia of the cell bodies, loss of glycogen. These changes were
      most pronounced around the central veins. Hepatocyte apoptoses also were
      observed. By immunohistochemistry an increased staining was seen for all P450
      isoforms tested (1A1, 2B1, 2E1, 3A2 and 4A1), predominantly perivenously and most
      pronounced after administration of the high doses without differences between
      Rcip, Scip or Raccip (preliminary results). By electron microscopy a moderate
      proliferation of peroxisomes after treatment with 1 mg/kg Cips with a ratio
      between mitochondria and peroxisomes of about 1:1 (controls: 10:1) was observed,
      and the peroxisomes were a more heterogeneous population. The relative portions
      of glycogen and both forms of the ER decreased. Treatment with 10 mg/kg Rcip,
      Scip or Raccip led to a strong increase in the number of peroxisomes, in some
      hepatocytes the ratio between mitochondria and peroxisomes was 1:3 with an
      increased heterogeneity among the peroxisomes evidenced by a broad range of
      electron densities. Most peroxisomes lacked a nucleoid. Thus, the biochemical
      effects differed only slightly and the morphological effects of the enantiomers
      were not different and were similar to those of the racemate.

PMID- 9784003
TI  - Expression of tenascin, fibronectin, and laminin in rat liver fibrogenesis--a
      comparative immunohistochemical study with two models of liver injury.
AB  - The aim of this study was to follow semiquantitatively by immunohistochemical
      means the alterations of the expression of the hepatic glycoproteins tenascin,
      fibronectin, and laminin in two different models of chronic liver injury, i.e.
      thioacetamide-induced liver cirrhosis and fibrosis after bile duct ligation. The
      tenascin distribution pattern observed during cholostasis-induced liver fibrosis
      showed some similarities, but also some differences in comparison with the
      results obtained after TAA intoxication. Most importantly, the data show that
      tenascin staining was detectable in almost all areas of the chronically injured
      livers up to 3 and 6 months in bile duct-ligated and chemically-injured livers,
      respectively. Thus, tenascin does not seem to play only a transient role in the
      fibrogenetic process as previously suggested. Laminin was strongly stained in
      proliferating ductules, whereas only a weak continuous distribution was observed
      along the sinusoidal wall. Furthermore, our findings confirm the role of
      fibronectin as a pacemaker of fibrosis. Regional differences in the kinetics of
      the expression of the glycoproteins may reflect local differences in their
      production by parenchymal or non parenchymal cells or regional patterns of
      proteolytic activity.

PMID- 9784004
TI  - Chromatographic resolution of ciprofibrate and interaction of the racemate and
      both enantiomers with rat liver microsomes in vitro.
AB  - The enantiomers of ciprofibrate may be achieved by enantioselective HPLC
      separation of its methylesters using a OD - Daicel column. Ciprofibrates
      (racemate and both enantiomers) bind to oxidized cytochrome P-450 in rat liver
      microsomes according type II like aniline or most probably as inversed type I,
      but less pronounced and with a general shift to the left. Ethylmorphine N
      demethylation, ethoxycoumarin and ethoxyresorufin O-deethylation are all
      inhibited by the ciprofibrates, most effectively ethoxyresorufin O-deethylation
      by S(-)-ciprofibrate even in microM concentrations. Microsomal luminol and
      lucigenin amplified chemiluminescence indicating the formation of reactive oxygen
      species, microsomal hydrogen peroxide formation and NADPH/Fe stimulated lipid
      peroxidation were inhibited in a concentration dependent manner in concentration
      ranges between mM and microM. This might be due to distinct scavenger activities
      of all 3 compounds: the zymosan stimulated chemiluminescence of whole blood was
      completely inhibited in mM concentrations and influenced significantly down to
      concentrations of 10 microM, whereas burst and phagocytosis tests with human
      polynuclear leucocytes were not influenced.

PMID- 9784005
TI  - Similarities between the uterine decidual reaction and the "mesenchymal lesion"
      of the urinary bladder in aging mice.
AB  - The histopathologic characteristics of the decidual reaction in the uterus of
      aging mice and the "mesenchymal lesion/tumor" in the urinary bladder of aging
      mice are compared and found to be very similar. Both lesions consist of spindle
      and epithelioid cells, may contain round eosinophilic granules and possess
      nuclear progesterone receptors and cytoplasmic desmin. The decidual reaction
      derives from endometrial stromal cells, while the "mesenchymal lesion" apparently
      develops from mesenchymal cells near the trigone area, carrying or developing
      progesterone receptors. If the hypothesis is accepted that in aging mice the
      uterine decidual reaction and the "mesenchymal lesion" in the urinary bladder
      represent an equivalent type of tissue reaction, then it follows that the typical
      "mesenchymal lesion" is not a tumor and could be called more specifically
      "decidual-like reaction".

PMID- 9784006
TI  - Histogenesis of nonurothelial carcinomas in the human and rat urinary bladder.
AB  - The histogenesis of nonurothelial carcinomas (squamous cell carcinoma, common
      adenocarcinoma, clear cell adenocarcinoma, signet ring cell adenocarcinoma and
      undifferentiated carcinomas) of the urinary bladder is difficult to understand,
      since the bladder is normally lined exclusively by transitional cell epithelium
      and contains no otherwise specified epithelia. In the present study we analysed
      the morphology and development of nontransitional cell carcinomas of the human
      and comparatively of the rat urinary bladder in an attempt to elucidate their
      histogenetic derivation. There is strong evidence that the underlying
      histogenetic principle consists in the well-known pluripotent metaplastic potency
      (squamous, columnar, goblet and signet ring cell, glandular and so-called
      nephrogenic metaplasia) of the normal and neoplastic urothelium as well, due to
      the complex embryologic origin of the bladder. Our findings indicate that
      squamous cell carcinomas, common and clear cell adenocarcinomas, and signet ring
      cell adenocarcinomas mainly arise secondarily from preexisting, predominantly
      solid transitional cell carcinomas by focally beginning and diffusely progressing
      metaplastic changes of various types. The second histogenetic pathway consists in
      the formation from primary metaplasias of the transitional cell epithelium in
      situ. Undifferentiated carcinomas (small, large and sarcomatoid subtypes) develop
      from preexistent solid urothelial carcinomas by a cellular dedifferentiation.
      Recognition of transitional cell carcinomas characterised by focal metaplastic
      processes or cellular dedifferentiation seems to be important from a clinical
      point of view, because of their probably more malignant biologic behaviour
      compared with uniformly differentiated pure urothelial carcinomas. Our
      comparative morphologic analysis of nonurothelial carcinomas and their
      histogenesis has demonstrated that the findings in the human and rat urinary
      bladder are largely identical. The experimental models used permit reliable
      extrapolation of the results obtained to the situation in man.

PMID- 9784007
TI  - The hepato-renal syndrome: renal amino acid transport in bile duct ligated rats
      (DL)--influence of treatment with triiodothyronine or dexamethasone on renal
      amino acid handling in amino acid loaded rats.
AB  - The influence of triiodothyronine or dexamethasone on renal amino acid handling
      was investigated in anaesthetized, bile duct-ligated (DL) adult female rats. 3
      days after DL, glomerular filtration rate (GFR) was unchanged whereas urine flow
      was decreased. Plasma concentrations of 5 out of 16 amino acids were
      significantly enhanced after DL. On the other hand, the fractional excretion (FE)
      of 11 out of 16 amino acids was significantly reduced as a sign of improved
      reabsorption capacity. Bolus injections of leucine (20 mg/100 g b.wt.), glutamine
      (45 mg/100 g b.wt.), or taurine (45 mg/100 g b.wt.) were followed by a temporary
      increase in the FE of the administered amino acids as well of the endogenous
      amino acids which were not administered. This phenomenon was more pronounced in
      DL than in control rats. Under load conditions, dexamethasone (60 microg/100 g
      b.wt.) or triiodothyronine (20 microg/100 g b.wt.) treatment for 3 days, i.p.
      once daily, was followed by a stimulation of renal amino acid reabsorption in DL
      rats. The increase in fractional amino acid excretion after amino acid load was
      significantly lower than in untreated rats. This effect was also more pronounced
      in DL rats.

PMID- 9784008
TI  - Regulation of parathyroid hormone-related protein expression in a canine squamous
      carcinoma cell line by colchicine.
AB  - The regulation of parathyroid hormone-related protein expression by colchicine,
      vinblastine, nocodazole, taxol, transforming growth factor-beta1 (TGFbeta1), and
      epidermal growth factor (EGF) was investigated in a canine squamous carcinoma
      cell line (SCC 2/88 cells). SCC 2/88 cells were stably transfected with a human
      P2/P3 PTHrP promoter-luciferase reporter gene construct and gene expression was
      measured after chemical treatments. The greatest increase in reporter gene
      expression was observed after colchicine treatment and small increases occurred
      after treatment with vinblastine, taxol, TGFbeta1, or EGF. Nocodazole had no
      significant effect on reporter gene expression. Colchicine also increased PTHrP
      steady state mRNA expression and PTHrP secretion by SCC 2/88 cells. These results
      demonstrated that PTHrP production was increased in SCC 2/88 cells by colchicine
      and suggested that factors or events during mitosis are capable of stimulating
      PTHrP production. An increase in PTHrP production during mitosis of malignant
      epithelial cells may be important in the pathogenesis of humoral hypercalcemia of
      malignancy.

PMID- 9784009
TI  - Telomerase activity in experimental animal tumors.

PMID- 9784010
TI  - Molecular mechanism of human stomach carcinogenesis implicated in Helicobacter
      pylori infection.
AB  - Genetic and epigenetic alterations in oncogenes, tumor suppressor genes, cell
      adhesion molecules, telomere and telomerase activity as well as genetic
      instability at several microsatellite foci are responsible for multistep process
      of human stomach carcinogenesis. The scenario of these alterations found in
      gastric cancer differs depending on the two histological types, indicating that
      different genetic pathways exist for well differentiated or intestinal type and
      poorly differentiated or diffuse type gastric cancers, even though both types of
      gastric cancer may arise from epithelial "stem cells" which express human
      telomerase reverse transcriptase (hTRT) and telomerase activity. Infection with
      Helicobacter pylori, which evidently causes the release of reactive oxygen
      species (ROS) and reactive nitrogen species (RNS), may be a strong trigger for
      "stem cell" hyperplasia in intestinal metaplasia, followed by telomere reduction
      and increase telomerase activity as well as hTRT overexpression. They may precede
      DNA replication error, DNA hypermethylation, CD44 abnormal transcript and p53
      mutations, all of which occur in at least 30% of intestinal metaplasia as early
      events of multistep pathogenesis of well differentiated type gastric cancer.

PMID- 9784011
TI  - Spontaneous neoplasms of the nasal cavity in rats.
AB  - The histomorphological features of two adenocarcinomas and two adenomas of the
      nasal cavity observed in two female Wistar rats and a male Sprague-Dawley rat are
      described. In one of the Wistar rats, a second tumour, classified as an adenoma,
      occurred in the posterior part of the nasal cavity.

PMID- 9784012
TI  - Odontogenic fibroma in Sprague-Dawley rats: a report of 2 cases.
AB  - Two cases of odontogenic fibroma occurring in aged Sprague-Dawley rats are
      described. Both neoplasms were associated with a maxillary incisor and had
      identical histomorphological features. They were composed of solid proliferations
      of primitive, dental pulp-like mesenchyme separated by areas of collagenization.
      Small strands and islands of mainly undifferentiated odontogenic epithelium
      immunostaining for keratins were scattered throughout both tumours. As a further
      characteristic, the lesions contained small foci of mineralization which were
      either cementum-like or resembled dysplastic dentin. The odontogenic fibroma
      represents a further type of odontogenic tumour in rats, which due to its typical
      histomorphology, can easily be differentiated from other odontogenic tumours such
      as ameloblastic odontoma or ameloblastoma.

PMID- 9784013
TI  - Vitamin E and C in the prevention of metal nephrotoxicity in developing rats.
AB  - The protective effect of vitamin E and C on sodium chromate (Cr) and thallium
      (Tl) induced nephrotoxicity was tested in 10- and 55-day-old rats. The
      concentrations of Cr and Tl were determined in renal cortex and medulla by atomic
      absorption spectrometry. Urinary volume and protein excretion as well as blood
      urea nitrogen (BUN) concentration were determined as parameters of
      nephrotoxicity. Cr and Tl induced nephrotoxicity was significantly more expressed
      in adult than in young rats. In Cr and Tl nephrotoxicity the protective effect of
      vitamin E was evident in both age groups. Vitamin E decreased Tl concentration in
      renal tissue. Therefore its protective effect is not to be attributed to its
      known antioxidant effect but to lower Tl concentration in renal tissue. Vitamin C
      was protective in Cr and Tl induced nephrotoxicity in adult rats without
      influence on metal concentrations in renal tissue. The dose necessary for
      protection against toxic Cr action in adult rats was not tolerated by young rats.
      The combined administration of both vitamins abolished the protective effect
      against Cr nephrotoxicity of the administration of each vitamin alone in adult
      rats. When vitamin E and C were administered in Tl treated adult and young rats
      the protective effect was the same as after the administration of each vitamin
      alone. Possible mechanisms are discussed.

PMID- 9784014
TI  - Plasma and buffy coat concentration of 8-methoxypsoralen in patients treated with
      extracorporeal photopheresis.
AB  - Recently, a new therapy involving an extracorporal activation of orally
      administered 8-methoxypsoralen (8-MOP), photosensitizing furocoumarin, is
      established for the treatment of different skin diseases, extracorporeal
      photopheresis (ECP). The pharmacokinetic profile of 8-MOP has been pursued as
      part of a clinical study which should assess the efficacy of ECP in patients with
      progressive systemic sclerosis and cutaneous T-cell lymphoma. The enormous intra
      individual variations proofed for plasma as well as buffy coat concentration are
      unfavourable for oral 8-MOP therapy. Therefore, the introduction of liquid 8-MOP
      formulation that allows the direct administration of the drug in to the treatment
      bag of the ECP device is challenging.

PMID- 9784015
TI  - Influence of hypoxia and hypoxia/hypercapnia upon brain and blood peroxidative
      and glutathione status in normal weight and growth-restricted newborn piglets.
AB  - Glutathione (reduced (GSH) and oxidized (GSSG)), lipid peroxidation products
      (TBAR) and in vitro production of reactive oxygen species (ROS, by means of
      stimulated lipid peroxidation, H2O2 formation and amplified chemiluminescence
      (CL) in 9000 xg brain supernatants) were studied in the cerebellum (C) and
      temporoparietal area (TP) of the brain of normal weight (NW) and spontaneously
      intra-uterine growth-restricted newborn piglets (IUGR) after 1 hour hypoxia
      (fractional inspired oxygen concentration (FiO2) 8%), and in combination with 10%
      CO2, followed by 3 hours recovery (FiO2 30%). The strong GSH depletion
      accompanied by an increased concentration of GSSG and TBAR, more distinct in
      IUGR, is the most important result in the brain after hypoxia and reoxygenation.
      Hypercapnia-related acidosis seems to protect the brain of IUGR from
      hypoxia/reoxygenation induced injury by reducing GSH depletion as well as GSSG
      and TBAR increases. But stimulated lipid peroxidation and H2O2 formation in 9000
      xg supernatants of C and TP were found to be higher in acidosis and hypercapnia.
      Decreased or unchanged amplified CL, demonstrating lower in vitro production of
      ROS, cannot explain the GSH depletion after hypoxia and reoxygenation. The scarce
      changes in erythrocyte GSH and GSSG as well as plasma TBAR concentrations did not
      reflect the findings in the brain. Nevertheless, the changes in the brain support
      the hypothesis that oxidative stress plays a role in neuronal damage after
      hypoxic stress, but the brain of IUGR did not reveal a special response to
      moderate hypoxia.

PMID- 9784016
TI  - Time course of the tilorone-induced lysosomal accumulation of sulphated
      glycosaminoglycans in cultured fibroblasts.
AB  - Dicationic amphiphilic drugs such as the immunomodulator tilorone [2,7-bis-[2
      (diethylamino)ethoxy]fluoren-9-one] are accumulated in lysosomes and disturb the
      degradation of sulphated glycosaminoglycans (GAGs) thus leading to generalized
      lysosomal GAG storage (mainly dermatan sulphate) in vivo and in cultured cells.
      In the present study, the time course of the tilorone-induced GAG storage was
      determined in cultured bovine corneal fibroblasts by a radiochemical approach and
      by morphological examination. In contrast to the rapid lysosomal accumulation of
      the drug as reported previously, it took approximately 42 h to reach 50% of the
      GAG storage obtained after 96 h. This is thought to be due to the fact that the
      temporal development of storage of undigested GAGs depends on the natural
      delivery of GAGs towards the lysosomal apparatus.

PMID- 9784017
TI  - Mitogenic short-term effects on hepatocytes and adrenocortical cells:
      phenobarbital and reserpine compared to carcinogenic and non-carcinogenic
      fluorene derivatives.
AB  - The adrenal cortex has a low physiologic cell renewal and shows only a moderate
      cell replication even after contralateral adrenalectomy. Although rather
      unsusceptible to the malignancy-inducing action of carcinogens, a single oral
      dose of various tumorigenic xenobiotics induced an additive mitotic response of
      adrenocortical cells studied after 48 h. Presently we report on three different
      response patterns in rats. First, a selective mitostimulation of the zona
      glomerulosa occured after reserpine associated with a loss of body weight, thymus
      and liver weight. These are unspecific stress effects and occur also after
      exogenous ACTH. Second, hepatomitogenic and liver-enlarging congeners, e.g.
      fluorene (FEN), fluorenone (FON) and 4-benzoyl-FON, but also the genotoxic 2
      acetylaminofluorene (2-AAF) and 2,4,7-trinitro-FON induced a selective mitotic
      response of the zona fasciculata (ZF). After the lowest effective dose of FEN or
      FON the afore-mentioned effects occured simultaneously, but were absent in the
      high dose group (only studied with fluorene). The 2-benzyl and 2-benzoyl
      substituted derivatives were ineffective at all. Third, a bizonal response was
      found only after phenobarbital (PB) or the lowest effective FEN dose. The
      preventive action of a low PB dose on the 2-AAF-induced ZF response indicates a
      modified metabolism. We conclude that the rapid mitotic ZF response is an
      endogenously mediated net effect of interactions between metabolic and various
      adaptive mechanisms. The latter are reported to be activated in a stressor
      dependent manner and converge in the adrenals. In this way the early mitotic ZF
      response could reflect indirectly 'specific' proliferation-prone properties of
      xenobiotics.

PMID- 9784019
TI  - Changes of renal taurine transport after treatment with triiodothyronine or
      dexamethasone in amino acid loaded rats.
AB  - In adult female anaesthetized rats, the influence of triiodothyronine or
      dexamethasone on renal amino acid (AA) handling was investigated in taurine (45
      mg/100 g b.wt.) loaded animals. Bolus injections of taurine were followed by
      temporary increase in fractional excretion (FE(AA)) of taurine as well of the
      endogenous amino acids which were not administered. Under taurine load
      conditions, triiodothyronine treatment (20 microg/100 g b.wt. for 3 days, i.p.
      once daily) was followed by a slight stimulation of the renal taurine
      reabsorption: the increase in FE(taurine) after taurine load was lower than in
      untreated rats. Dexamethasone (60 microg/100 g b.wt. for 3 days, i.p. once daily)
      was without significant effect on FE(taurine) in taurine loaded rats. In non
      taurine loaded rats there was no hormone influence at all. Similarities and
      differences between the effects of bolus injections of taurine, glutamine, and
      leucine on the FE(AA) of these three amino acids were compared in detail to
      further clarify the reason for the increased amino acid reabsorption capacity
      after pretreatment with triiodothyronine or dexamethasone.

PMID- 9784018
TI  - Impact of CYP2E1 genotype in renal cell and urothelial cancer patients.
AB  - Genetic polymorphisms of enzymes involved in carcinogen metabolism have been
      found to influence susceptibility to cancer. Ethanol-inducible CYP2E1 is an
      enzyme of major toxicological interest because it metabolizes several drugs,
      precarcinogens and solvents to reactive metabolites. In the present study, we
      investigated the cytochrome P450 2E1 genetic polymorphism in renal
      cell/urothelial cancer patients from two German regions, Jena and Halle,
      different with respect to their environmental pollution degree in comparison with
      healthy controls from the same regions. DNA of peripheral white blood cells was
      isolated both from 224 renal cell/urothelial cancer patients and 304 controls. We
      focussed on polymorphisms in the promoter region and intron 6 of the CYP2E1 gene.
      The polymorphisms were identified as RFLP's by amplification of the appropriate
      DNA fragment and subsequent digestion with the restriction enzymes PstI, RsaI and
      DraI. In Jena as well as in Halle, the frequency distributions of the PstI/RsaI,
      DraI and combined DraI + PstI/RsaI genotypes showed no significant differences
      between controls and renal cell/urothelial cancer patients. We did not find
      significant differences between Jena and Halle. 86.2% of all subjects with a
      homozygote PstI/RsaI genotype also carried a heterozygote DraI genotype, whereas
      5.1% of the subjects with a heterozygote PstI/RsaI genotype also carried a
      heterozygote DraI genotype. Renal cell cancer as well as urothelial cancer risk
      was not elevated in patients with heterozygote DraI, PstI/RsaI and combined DraI
      + PstI/RsaI genotypes (odds ratios slightly insignificantly increased).
      Interestingly enough, an association between these polymorphisms and renal cell
      cancer risk was found in the female subgroup but not in the male subgroup. The
      basis of these sex-specifically increased risks are different frequencies
      concerning heterozygote and homozygote genotypes in controls and cancer patients.
      In controls, the heterozygote genotype frequency was lower in females than in
      males. In renal cell cancer patients, the results were quite the contrary.
      Summing up, our results demonstrate an lack between CYP2E1 genetic polymorphism
      and renal cell/urothelial cancer risk.

PMID- 9784020
TI  - Application of cryopreserved precision-cut liver slices in pharmacotoxicology-
      principles, literature data and own investigations with special reference to
      CYP1A1-mRNA induction.
AB  - Principle steps necessary for cryopreservation of precision-cut liver slices as
      currently applied by different groups are summarized including own results
      concerning mode of freezing. Now we use rapid freezing by immersion in liquid
      nitrogen after exposure to 10% DMSO as the cryoprotectant for rat liver slices.
      The results indicate well-maintained cytochrome P450 (CYP)-dependent deethylation
      rates in slice homogenate after short-term incubation. ECOD rate in intact thawed
      slices was even higher than in fresh ones after 2 h incubation. In contrast to
      fresh slices all parameters except protein content decreased to marginal levels
      during long-term incubation of thawed slices for 24 h. The first preliminary
      experiments on albumin secretion by thawed rat liver slices, measured between the
      2nd and the 4th hour of incubation, showed partial maintenance of this liver
      specific differentiated function. Trials to induce CYP1A1 in thawed rat liver
      slices in vitro by beta-naphthoflavone (BNF) resulted in increased expression of
      CYP1A1-mRNA within 6 h as shown by RT-PCR and quantified by competitive RT-PCR.
      The decline of deethylation rates, determined in slice homogenates, and of
      viability within 24 h incubation was not prevented by exposure to BNF or DMSO.
      The results derived from one sample of cryopreserved human liver slices indicate
      a quite acceptable maintenance of function up to 6 h, if the same protocol as
      developed for rat liver slices was used.

PMID- 9784021
TI  - In vitro investigations of drug release and penetration--enhancing effect of
      ultrasound on transmembrane transport of flufenamic acid.
AB  - Percutaneous absorption studies are performed in various in vitro models to
      determine the rate of drug absorption via the skin. We designed an phonophoretic
      drug delivery system to investigate the influence of ultrasound on transmembrane
      transport of different drugs. Phonophoresis is defined as the migration of drug
      molecules, contained in a contact agent, through the skin under the influence of
      ultrasound. 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. Flufenamic acid was determined by using a fluorimetric method.
      Ultrasound energy was supplied for between 5 and 30 min at a range of intensities
      (0; 0.3; 0.6; 0.9; 1.2; 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 level studied. The time of
      application was found to play an important role in delivery and transport of
      drug. Dependent on time, we observed an arise of temperature up to 4.5 degrees.
      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 in 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.

PMID- 9784022
TI  - Adverse drug reaction monitoring in Jena--experiences of a regionalized
      pharmacovigilance centre.

PMID- 9784023
TI  - Approaches to the replacement of ethinylestradiol by natural 17beta-estradiol in
      combined oral contraceptives.
AB  - The strong hepatic estrogenic actions of ethinylestradiol (EE) are very likely to
      be the cause of the cardiovascular morbidity related to the use of combined oral
      contraceptives (COCs). This survey presents results of EE replacement in COCs
      with natural 17beta-estradiol (E2) in the following stages: reduction of EE to
      daily doses of 0.01 mg and concomitant replacement with E2 (as valerate, EV),
      complete replacement of EE with E2 using a novel multiphasic combination
      containing EV and the progestin dienogest (DNG), and the use of natural E2 to
      develop estrogen sulfamates (J 995) showing sufficient dissociation of uterine
      from liver estrogenicity. Recent data from preclinical and clinical studies show
      that these approaches seem to be promising.

PMID- 9784024
TI  - Influence of 2-acetylaminofluorene (2-AAF) on biotransformation and lipid
      peroxidation in salivary glands and liver from male rats.
AB  - Salivary glands proved to be active in biotransformation. In microsomes of rat
      salivary glands 7-ethoxyresorufin O-deethylation (EROD) and 7-pentoxyresorufin O
      depentylation (PEROD) were detectable, but with much lower activities than in the
      liver. Beside the well-known induction of EROD or PEROD in the liver by beta
      naphthoflavone (BNF) or phenobarbital (PB), respectively, a marked rise in EROD
      rate of salivary glands was observed after BNF treatment. Administration of 2-AAF
      caused an increase in EROD rates in liver microsomes, but a decrease in
      microsomes of salivary glands. This decrease in EROD rate was accompanied by
      selective cytotoxic damages in the convoluted granulated tubules of the
      submandibular glands. No cytotoxic damage occurred in the submandibular glands
      after a combined administration of the inducer BNF and 2-AAF. This indicates
      relations between these toxic effects of 2-AAF and changes of 2-AAF-metabolism in
      BNF-induced rats, maybe in the liver and/or in the submandibular glands
      themselves.

PMID- 9784025
TI  - In vitro toxicity of surfactants in U937 cells: cell membrane integrity and
      mitochondrial function.
AB  - Surface-active agents are components of many drugs and cosmetics. In order to
      examine their cytotoxic and membrane-toxic potential, various surfactants were
      examined in U937 cells using the tetrazolium reduction assay EZ4U, a modified XTT
      test, and the arachidonic acid release test (AART). EZ4U measures the ability of
      living cells to reduce a colorless tetrazolium salt to an orange water-soluble
      formazan derivative by mitochondrial dehydrogenases. [3H]arachidonic acid
      ([3H]AA) is rapidly incorporated into cell membrane phospholipids. Due to
      membrane disintegration or enzymatic catalysis, it is released into the cell
      culture medium and can be measured by scintillation technique. The results after
      24-hour-exposure are as follow (CC50 microg/ml; RC50 microg/ml): benzalkonium
      chloride (0.6), Cremophor A25 (1.4; 5.9), sodium cetearyl sulfate (1.6; 19.9),
      Brij78 (1.6; 7.7), TEGO betaine E (3.0; 19.3), TEGO betaine CKD (4.1; 20.2), TEGO
      betaine L7 (7.5; 20.0), sodium dodecyl sulfate (7.5; 39.0), Triton X-100 (8.9;
      110), polysorbate 80 (48.1; 491), soybean lecithin (7920; 19940).

PMID- 9784026
TI  - Plasma levels of glutathione, alpha-tocopherol and lipid peroxides in
      polytraumatized patients; evidence for a stimulating effect of TNF alpha on
      glutathione synthesis.
AB  - Prognosis and outcome of polytraumatized patients are determined by the possible
      development of multiple organ failure (MOF). Among the direct traumatic organ
      damage, it is caused by a systemic inflammatory reaction. This might be triggered
      by an activation of the inflammatory mediator cascade following hemorrhagic
      traumatic shock as well as by oxygen-derived free radicals (ROS). The aim of our
      present study was to answer the following questions: 1. Is the "oxidative stress"
      measurable during the development of MOF after polytraumatic injury? 2. Is there
      a relation between the activation of the inflammatory mediator cascade and
      changes of the organism's antioxidative system? The study group included 26
      patients (15 survivors, 11 non-survivors) suffering from severe polytraumatic
      injury (Hannover Polytrauma Score 12-63 points). Plasma levels of reduced (GSH)
      and oxidized (GSSG) glutathione alpha-tocopherol (TOC), lipid peroxides
      (expressed in terms of thiobarbituric acid reagible substances = TBARS), and
      tumor necrosis factor alpha (TNF) were measured each day from the point of
      admission on the ICU until the discharge or death of the patients. The following
      results were obtained: Independent from the outcome, we observed a continuous
      loss of plasma sulfhydryl groups and TOC. In the patients developing a MOF score
      > 5 on 10th day after injury (n = 6), a significant increase in plasma GSSG level
      was measurable. Additionally, a total loss of plasma GSH was seen in some of
      these patients indicating the collapse of the GSH-dependent antioxidative system.
      Similar changes were never observed in patients with MOF score < or = 5 on 10th
      day after injury (n = 15). In this group, a significant correlation between
      plasma TNF peaks and short time GSH boosts was obtained as a possible indicative
      for a stimulating effect of TNF on GSH synthesis. It can be concluded that
      processes of oxidative stress in connection with a consumption of endogenic
      antioxidants might be able to promote the development of MOF after polytraumatic
      injury.

PMID- 9784027
TI  - Is there a beneficial effect of the calcium channel blocker diltiazem on
      cyclosporine A nephrotoxicity in rats?
AB  - To investigate whether or not there is a beneficial effect of diltiazem (D) on
      cyclosporine A (CsA) nephrotoxicity, renal function, CsA blood levels, and
      effects of CsA on biotransformation in the liver and on lipid peroxidation were
      characterized in rats. A single administration of D (60 mg/kg b.wt.) reduced
      urinary volume (UV), GFR and excretion of Na+ and K+, whereas a single dose of
      CsA (60 mg/kg b.wt.) alone had no respective effects. P-aminohippurate excretion
      was almost equal in all groups. Lower doses of D (and CsA) were without effects.
      After repeated CsA treatment a retardation in body weight gain was seen, with
      little effect of a co-administration with D hereon. In all tests, thymus mass was
      reduced by CsA, the weight of spleen, liver, adrenal glands, and kidney were not
      generally affected by any of the treatments. Furthermore, after repeated
      administration of CsA and/or D, urinary volume, GFR and Na+ excretion were
      reduced by CsA, too. Electrolyte concentrations in plasma showed no evident
      changes by any of the treatments for Na+ and Ca2+. After long time treatment, CsA
      and CsA + D quite similarly led to higher K+ but lower Mg2+ concentrations in
      plasma. Only with 7 days highest dosage treatment PAH excretion was reduced
      significantly by CsA and CsA + D treatment. Surprisingly, CsA levels measured in
      blood and in kidney tissue, showed lower values after co-administration with D
      compared to CsA treatment alone. This could be caused by higher activities of
      monooxygenase functions revealed after pretreatment with D alone. Reduced
      glutathione (GSH) contents in kidney were elevated in CsA and CsA + D treated
      groups. In general no significant differences were to be observed concerning
      lipid peroxidation and stimulated H2O2 formation. Altogether evident protective
      effects of diltiazem on CsA nephrotoxicity in rats could not be proven.

PMID- 9784028
TI  - Induction of cytochrome P450 1A1 in rat liver slices by 7-ethoxycoumarin and 4
      methyl-7-ethoxycoumarin.
AB  - 7-Ethoxycoumarin (EC) is widely used as a model substrate for monooxygenase
      function, its O-deethylation representing cytochrome P450 (P450) activity mainly
      of 1A but also of 2B isoforms. Reports on investigations of its own capacity to
      induce or suppress P450 activities, however, have not been found in biomedical
      literature. To avoid the influence of in vivo pharmacokinetics, studies can well
      be undertaken with liver slice incubation. Therefore in the present investigation
      precision-cut rat liver slices from male 43-63-day-old male HAN:Wistar outbred
      rats were incubated at 30 degrees C in carbogen saturated William's Medium E for
      24 h. EC was added previously to final concentrations of 10, 25, 50, 75 or 100
      microM. After incubation, homogenate was prepared from slices and used for model
      reactions (7-ethoxyresorufin O-deethylation [EROD] and 7-pentoxyresorufin O
      depentylation [PROD]). EROD, indicating activities of 1A isoforms, was enhanced
      by incubation with EC at 25 and 50 microM to about doublefold but showed control
      or lower values at 75 and 100 microM. Incubation with beta-naphthoflavone in
      comparison led to variable increases (3-5-fold of controls). For PROD as an
      indicator of the phenobarbital inducible P450 isoforms 2B1 and 2B2 no enhancement
      was found, but a decrease by incubation with 75 and 100 microM EC. To further
      investigate the correlation between enzyme activity and gene expression after
      slice incubation, P450 1A1 mRNA content was measured by RT-PCR. Induced gene
      expression for 1A1 was seen with different EC concentrations to a variable
      extent, though not as strong as with BNF. Similar incubation with 4-methyl-7
      ethoxycoumarin revealed an even stronger induction of EROD activity with maxima
      at about 10-32 microM, reaching BNF values. In contrast incubation with 7
      benzyloxycoumarin had no evident inducing or suppressing effect, neither on EROD
      nor on PROD activity.

PMID- 9784029
TI  - Inhibition of thrombin-induced contractile responses by protein kinase inhibitors
      in porcine pulmonary arteries.
AB  - The clotting enzyme thrombin is known to cause receptor-mediated contractile
      effects in isolated blood vessels. In the present studies the influence of
      protein kinase inhibitors on the contractile response of porcine pulmonary
      arteries to thrombin (3 U/ml) was investigated. Endothelium-denuded rings (2-3
      mm) from small arteries were placed in organ baths for isometric tension
      recording. The vessels were preincubated for 30 min with the inhibitors before
      inducing contractions. In the presence of the protein kinase C (PKC)-inhibitors
      staurosporine, BIM I (bisindolyl-maleimide I), chelerythrine and Ro 31-8220 (1
      microM each), the contractile responses to the PKC activator phorbol 12,13
      dibutyrate (PDBu; 50 nM) were diminished by 70-100%. However, for inhibition of
      thrombin-induced contractions generally higher concentrations of the inhibitors
      were required. Only staurosporine at 1 microM inhibited the thrombin effect by
      about 75%. The tyrosine kinase inhibitor erbstatin (30 microM) did not
      significantly alter the thrombin effect, whereas genistein at 10 microM caused a
      significant inhibition of contractile responses to both thrombin and PGF2alpha.
      At 100 microM genistein also inhibited the contractile effects of PdBu and KCl.
      These studies suggest that activation of both PKC and non-receptor tyrosine
      kinases seems to be involved in the signal transduction pathways of thrombin
      induced contractile effects in isolated vessels.

PMID- 9784030
TI  - Investigation on possible antioxidative properties of the NMDA-receptor
      antagonists ketamine, memantine, and amantadine in comparison to nicanartine in
      vitro.
AB  - Possible antioxidative properties of three N-methyl-D-aspartate (NMDA)-receptor
      antagonists, the anesthetic ketamine and the antiparkinson drugs memantine and
      amantadine were investigated in vitro on the microsomal cytochrome P450 (P450)
      system of rat livers and on rat whole blood chemiluminescence in comparison to
      nicanartine, a substance with known antiatherosclerotic, hypolipemic and
      antioxidative capacity. For this purpose, the effects on NADPH- and iron
      stimulated lipid peroxidation (LPO), hydrogen peroxide (H2O2) production, and
      NADPH- and iron-stimulated lucigenin (LC) and luminol (LM) amplified
      chemiluminescence (CL) were examined using rat liver microsomes. Additionally,
      the influence on LM amplified whole blood chemiluminescence after zymosan
      activation of polymorphonuclear leukocytes (WB-CL) was investigated. Furthermore,
      binding to P450 and effects on P450 mediated monooxygenase function, as measured
      by the model reactions ethoxyresorufin O-deethylation (EROD), ethoxycoumarin O
      deethylation (ECOD), and ethylmorphine N-demethylation (END), were assessed.
      Nicanartine concentration dependently reduced LPO and H2O2 production already at
      a concentration of 1 microM, whereas LC and LM amplified CL and WB-CL were not
      affected. EROD and END were concentration dependently diminished starting at 1
      microM, and ECOD already at 0.1 microM. Ketamine decreased LPO, H2O2 production
      and LM and LC amplified CL, starting at 100 microM. WB-CL was significantly
      diminished already at 10 microM. EROD and ECOD were inhibited at 10 and 100
      microM and END at 100 microM. With memantine a concentration dependent inhibition
      of LPO and WB-CL was seen at 100 and 1000 microM and a reduction of LC and LM
      amplified CL only at 1000 microM. H2O2 production was not affected. EROD and ECOD
      were significantly diminished by a concentration of 100 microM. No effect was
      observed on END. Amantadine significantly reduced LPO and WB-CL, but only at 1000
      microM. H2O2 production and LC and LM amplified CL were not affected. EROD was
      significantly diminished at 100 microM, whereas no influence was seen on ECOD and
      END. Nicanartine displayed type II or reverse type I, ketamine, memantine and
      amantadine type I substrate binding to P450. The highest binding affinity to P450
      was seen with nicanartine, followed by ketamine, memantine and then amantadine.
      These results demonstrate, that all four substances seem to act as radical
      scavengers and/or as inhibitors of the oxidative function of P450. All four
      substances seem to interfere with the monooxygenase function of P450. This may
      result in a possible influence on the biotransformation of endogenous as well as
      of foreign compounds. The effects of nicanartine were much more pronounced than
      those of ketamine, memantine, and amantadine.

PMID- 9784031
TI  - Monooxygenation, cytochrome P450-mRNA expression and other functions in precision
      cut rat liver slices.
AB  - Precision-cut rat liver slices (KRUMDIECK slicer, slice thickness 200-250 microm)
      were incubated in rollers containing modified William's medium E at 37 degrees C
      for 2, 24 and 48 hrs. Protein, DNA, potassium and glutathione concentrations did
      not decrease during 48 hrs. Lactate dehydrogenase (LDH) leakage into the medium
      was relatively marked during the first 2 hrs of incubation, from the 2nd to the
      48th hr LDH leakage was very low. The same is true of the release of
      thiobarbituric acid-reactive substances. Albumin synthesis and transport into the
      medium decreased to about 70% after 48 hrs. Cytochrome P450 (CYP)-dependent 7
      ethoxycoumarin O-deethylation rate was relatively stable up to 48 hrs, whereas
      testosterone hydroxylation decreased significantly without alterations of the
      proportions of the 7 quantified hydroxylated metabolites. After exposure of the
      slices to beta-naphthoflavone for 6 hrs CYP1A1-mRNA expression, measured by
      competitive RT-PCR, was increased by a factor of at least 1000. Precision-cut
      liver slices are a useful tool for the study of various hepatic functions, drug
      metabolism and its induction in vitro.

PMID- 9784032
TI  - Immunohistochemical localization of cytochrome P450 1A1 in precision-cut rat
      liver slices after in vitro exposure to beta-naphthoflavone.
AB  - Mono- and polyclonal antibodies have been used to study the localization and
      distribution of cytochrome P450 1A1 (CYP1A1) in cultured precision-cut liver
      slices with various immunohistochemical methods. Neither in non-incubated slices
      nor in slices incubated in the absence of beta-naphthoflavone (BNF) for 24 hrs
      was CYP1A1 immunohistochemically detectable. After incubation in the presence of
      BNF (25 microM), however, CYP1A1 was well visible in parenchymal and biliary
      epithelial cells. CYP1A1 was not evenly distributed, but was localized
      predominantly in hepatocyte layers near the surfaces of the slices. This
      distribution could be due to the preferential uptake of BNF by outer cell layers
      or due to functional changes of inner cells. Together with results obtained with
      other methods (e.g. RT-PCR) this investigation also demonstrates that precision
      cut liver slices are a useful tool for the detection of in vitro induction of
      CYP1A1.

PMID- 9784033
TI  - Liver fibrosis in guinea pigs experimentally induced by combined copper and
      aflatoxin application.
AB  - Aflatoxin B1 alone (0.05 mg resp. 0.037 mg/kg/d), copper alone (6.6 mg/kg/d or
      200 mg/l drinking water) or a combination of both was administrated orally for 6
      months to young guinea pigs from the first/second day of life. In the copper
      group there were no pathomorphological changes. For the aflatoxin B1 group liver
      damage was established. In the combined group liver injury was more frequent and
      more severe compared to the aflatoxin B1 group. Compared with the copper group
      biliary copper excretion was diminished and the kidney copper content was
      elevated in the Afl. B1 + Cu group. While copper concentrations in bile and
      kidney correlated with other parameters, notably the pathological lesions of the
      liver, no such correlation was found for liver copper. Therefore in this
      experiment the degree of Cu accumulation was not decisive for the liver lesions.
      The livers' capacity for excreting Cu by bile seems to be a much more important
      factor. Histologically only the livers of the combined group exhibited
      degeneration, atrophy and steatosis of liver cells, and a fibrosis more or less
      pronounced. For childhood cirrhosis (ICC and ICT), a combined etiology--a liver
      damaging agent plus elevated alimentary copper--is a plausible hypothesis.

PMID- 9784034
TI  - Obsessive-compulsive disorders in dermatology.
AB  - BACKGROUND: Until the 1980s, obsessive-compulsive disorders (OCD) were considered
      rare and almost impossible to treat, but it is now recognized that they are
      frequently encountered and can respond to treatment. Many OCD involve the skin
      and are therefore observed by dermatologists: we call them dermo-OCD (DOCD).
      However, despite this, there are few reports in the dermatological literature and
      the majority are by American authors. OBJECTIVE: The aim of this paper is to
      offer a critical rediscussion of the diagnostic picture of this pathology on the
      basis of a review of the literature and the clinical observations of the authors.
      The main difficulties that dermatologists may encounter are described and some
      therapeutic guidelines are given. CONCLUSIONS: A large number of OCD are
      frequently observed by dermatologists, but not all of them are recognized as
      DOCD.

PMID- 9784035
TI  - Efficacy and safety of itraconazole pulse therapy: Brazilian multicentric study
      on toenail onychomycosis caused by dermatophytes.
AB  - BACKGROUND: Itraconazole is a large spectrum triazole with known efficacy in both
      continuous and pulse therapy for various mycoses. OBJECTIVES: Evaluate the
      efficacy and tolerability of itraconazole pulse therapy for onychomycosis of the
      toenails due to dermatophytes, in a prospective, open, non-comparative and
      multicentric investigation. Patients and methods The trial was completed by 72
      patients of an initial total of 89. Treatment consisted of four cycles of
      itraconazole, 200 mg twice a day, for seven consecutive days each month. Patients
      were evaluated clinically, mycologically and biochemically before, during and at
      the end of the investigation, and were divided into two groups according to the
      measure of normal portion of the most affected nail (target nail), as follows:
      Group 1: 0-5.9 mm; and Group 2: more than 6 mm. RESULTS: Improvement was
      satisfactory and progressive. Results were statistically significant, when
      comparing the three moments of the study: pre-treatment, end of therapy (fourth
      month) and follow-up (ninth month) in both groups. CONCLUSIONS: Itraconazole
      pulse therapy was efficient and safe for the treatment of onychomycosis caused by
      dermatophytes, although a much higher daily dosage than the known continuous
      administration was used. Group 1, with nails initially more extensively affected,
      had a more evident improvement, by the mean variation in millimeters of normal
      portion of the target nail. This group showed a very satisfactory response,
      although not reaching total cure, thus demonstrating the great importance of
      early treatment of this disease. A residual therapeutic effect is maintained even
      after suspension of the drug. Group 2 obtained better total cure rates, and four
      pulses were, in general, sufficient, whereas more cycles would have been
      beneficial for the Group 1 patients with more extensive involvement.

PMID- 9784037
TI  - In vivo and in vitro investigations of hydration effects of beauty care products
      by high-field MRI and NMR microscopy.
AB  - AIM: Data obtained from in vivo and in vitro measurements on human skin and skin
      samples are presented. METHODS: In vivo measurements, using a 3-Tesla magnetic
      resonance system, on the forearm of three female volunteers show an increase of
      signal intensity, after application of cream, between 30% and 58%, depending on
      the cream type. In-plane resolution was 90 microm, with slice thickness of 2 mm.
      Chemical-shift-selective in vitro microimaging studies were performed on a 9.4-T
      spectrometer using human skin samples from the abdomen. In these experiments, in
      plane resolution was 4 microm and slice thickness was 100 microm. RESULTS: The
      results demonstrate clearly the moisturising effect of beauty care products on
      the stratum corneum, which can be identified in in vitro experiments. No ingress
      into the skin of the lipid components of the emulsions could be observed in
      vitro. However, skin occlusion and consequently a long-lasting moisturising
      effect cannot be excluded. CONCLUSIONS: These results prove the capability of
      magnetic resonance imaging to investigate human skin in vivo and in vitro, and to
      follow the skin penetration of beauty-care products and pharmaceutical ointments.

PMID- 9784036
TI  - Medium dose isotretinoin for the treatment of acne.
AB  - BACKGROUND: Although the efficacy of isotretinoin in the treatment of acne is
      unquestioned, improvement of patient tolerance and acceptance of the drug are
      desirable. Furthermore, no data on acne-induced scarring during isotretinoin
      treatment are available. AIM: In the present study, we have evaluated the
      efficacy and tolerability of an initial stepwise incremental (n = 83) or an
      initial high dose (n = 11) and a subsequent medium maintenance dosing of
      isotretinoin in outpatients treated for acne over a 7 year period. METHODS:
      Ninety-four patients with moderate to severe acne were treated for a mean
      duration of 8.3 months, at a mean daily dose of 31.4 mg. Follow-up and final
      evaluation were done during outpatient visits and with a standardized patient
      questionnaire. RESULTS: Response to treatment was very good in 62.8% and good in
      31.9% of patients, with only one treatment failure. Of the patients, 21.3%
      required retreatment after a mean interval of 7.7 months. Four patients refused
      or dropped out from treatment, 27% noted initial mild worsening of their acne,
      and none experienced severe adverse effects. Scars were present in 89.4% of
      patients, with improvement occurring in 67.9% during treatment. CONCLUSION: The
      altogether good to excellent clinical response of acne lesions and acne scars,
      with a low side effect profile, warrants further study of this simple, modified
      treatment regimen in patients with acne and acne-induced scarring.

PMID- 9784038
TI  - Imedeen in the treatment of photoaged skin: an efficacy and safety trial over 12
      months.
AB  - BACKGROUND: UV-exposure induces photoaging of the skin. OBJECTIVE: Testing the
      efficacy and safety of oral Imedeen in photoaged skin. METHODS: Three month
      placebo-controlled randomized study of 144 subjects and 9-month-uncontrolled
      continuation. Efficacy measurements included clinical evaluation, self
      evaluation, photograph evaluation, as well as ultrasound, transepidermal water
      loss and replica measurements. RESULTS: After 3 months, no significant effects
      were detected. One years treatment gave significant improvement compared with
      baseline in investigator's evaluation of fine lines and overall photoaging, in
      photograph evaluation of fine lines, overall photoaging, telangiectasia and
      hyperpigmentation, in self-evaluation of skin condition, density measurements by
      ultrasound, trans-epidermal water loss and skin smoothness from analysis of skin
      replica. No serious side-effects related to treatment were reported. CONCLUSION:
      Imedeen appears effective and safe for treatment of photoaged skin.

PMID- 9784039
TI  - The use of azathioprine in severe adult atopic eczema.
AB  - AIM: To evaluate the use of azathioprine in the treatment of severe adult atopic
      eczema and review the relevant literature. BACKGROUND: Effective treatment of
      severe adult atopic eczema may necessitate the use of agents such as systemic
      steroids, PUVA or cyclosporin, which are associated with significant morbidity.
      Azathioprine is an effective alternative which can induce disease remission and
      may be less toxic. METHODS: Ten patients treated with azathioprine 0.7-2.5 mg/kg
      per day for a minimum period of 12 months were evaluated in a retrospective
      follow-up study. RESULTS: Clearance or marked improvement was noted in eight
      patients; three of these later became refractory to the drug. Side-effects were
      few and were well-tolerated. One patient was found to have lymphoma 8 months
      after stopping treatment. CONCLUSION: Azathioprine is an effective and cheaper
      alternative to cyclosporin in the treatment of severe adult atopic eczema. Its
      long-term toxicity remains unclear.

PMID- 9784040
TI  - Efficacy, safety and tolerability of terbinafine for Tinea capitis in children:
      Brazilian multicentric study with daily oral tablets for 1,2 and 4 weeks.
AB  - BACKGROUND: Tinea capitis is a common skin disease seen predominantly in
      children. The standard therapies for this disease are griseofulvin and
      ketoconazole. Nevertheless, these drugs have drawbacks in that they are only
      fungistatic and require treatment for at least 6 weeks. Previous studies with
      oral terbinafine for the treatment of Tinea capitis have shown that this agent is
      effective when given for 4 weeks, comparable to an 8-week regimen with
      griseofulvin. To date there is no data on the use of oral terbinafine in
      Brazilian children. OBJECTIVES: To assess the efficacy, safety and tolerability
      of oral terbinafine in short-term treatments (1-, 2- and 4-week treatment) of
      Tinea capitis in children. PATIENTS AND METHODS: One hundred and thirty-two
      children aged 1-14 years were enrolled in this study, but only 107 were
      considered for the final efficacy analysis. Diagnosis included clinical
      assessment and examination by Wood's light. Confirmation was obtained by direct
      microscopy and culture for fungus. Terbinafine dosage (125 or 250 mg/day) was
      adjusted according to patient weight. Efficacy was evaluated both by clinical and
      mycological assessment. Safety and tolerability variables included data on
      adverse reaction and clinical laboratory evaluations. RESULTS: Mycological
      evaluation in the follow-up visit at week 12 showed negative direct microscopy
      and culture results in 48.6, 60.5 and 69.7% patients in groups 1-, 2- and 4-week,
      respectively (n.s.). At week 12, 84.8% patients in group 4-week achieved clinical
      cure with a significant difference compared to groups 1- and 2-week, 54.3 and
      60.5%, respectively (P < 0.01). Adverse reactions were present in 4.8, 6.8 and
      10.9% of patients in groups 1-, 2- and 4-week, respectively. terbinafine was not
      associated with clinically relevant increases in liver function tests.
      CONCLUSIONS: Terbinafine is an effective, well tolerated and safe antifungal
      agent for the treatment of Tinea capitis in children. The shorter duration of
      treatment resulted in lower cure rates. However, it is important to note that
      depending on the severity of the disease, a 1-week-only treatment can also be
      effective in this indication.

PMID- 9784041
TI  - Bullous erythema multiforme following herpes zoster and varicella-zoster virus
      infection.
AB  - Four cases of herpes zoster-induced bullous erythema multiforme (EM) are
      reported. Three patients presented with widespread skin lesions 10 to 14 days
      after an episode of thoracic herpes zoster. In these patients a high increase in
      varicella-zoster virus (VZV) antibody titer was detected, indicating secondary
      VZV infection. Histologic examinations of skin biopsy from a patient with
      widespread lesions (case 4) revealed a mixture of EM, toxic epidermal necrolysis
      and herpetic virus infection. VZV should be included in the list of infectious
      agents able to trigger EM and Stevens-Johnson syndrome.

PMID- 9784042
TI  - Cutaneous angiomyolipoma: report of two cases with emphasis on HMB-45 utility.
AB  - BACKGROUND: Angiomyolipomas are tumors composed of adipose tissue, blood vessels
      and smooth muscle. Although renal angiomyolipomas are well known, cutaneous
      tumors have been described only recently. HMB-45 reactivity, reported for renal
      angiomyolipomas, has been suggested as a useful tool in differential diagnosis.
      OBJECTIVE: Two cases of cutaneous angiomyolipoma are described and investigated
      for HMB-45 reactivity. METHODS: Conventional histochemical and
      immunohistochemical methods were used. RESULTS: Immunohistochemical analysis
      showed no reactivity for HMB-45 antibody. CONCLUSION: We conclude that, unlike
      renal angiomyolipomas, HMB-45 reactivity is not helpful in differentiating
      cutaneous angiomyolipomas.

PMID- 9784043
TI  - Small malignant melanoma in patients with mycosis fungoides.
AB  - An increased risk for a second malignancy has been reported in patients with
      mycosis fungoides. We describe two subjects with mycosis fungoides who developed
      small malignant melanoma after topical application of nitrogen mustard.

PMID- 9784044
TI  - Disseminated skin infection due to Mycobacterium fortuitum in an immunocompetent
      patient.
AB  - Skin infections caused by atypical rapid-growing mycobacteria, which used
      considered to be unusual, have become more frequent, especially in
      immunodepressed patients. Clinical cutaneous disease with these pathogens seems
      to follow two patterns: in the immunocompetent host, a traumatic injury is
      followed by the development of localized abscess formation; but in the
      immunocompromised individual there is no history of trauma and the patient
      presents with multiple subcutaneous nodular lesions. We describe a rare case of
      an immunocompetent young woman with disseminated skin infection due to
      Mycobacterium fortuitum. We emphasize the diagnostic and therapeutic problems
      associated with such infections.

PMID- 9784045
TI  - Effective treatment of persistent papular acantholytic dermatosis with
      cyclosporine.
AB  - We describe a patient with persistent papular acantholytic dermatosis provoked by
      phototoxic reaction to his usual perfumed soap and shaving foam. Therapy with
      systemic and topical corticosteroids failed to improve the patient. Treatment
      with cyclosporine was found to be effective.

PMID- 9784047
TI  - Antibodies to desmoplakin in a patient with pemphigus foliaceous.
AB  - BACKGROUND: Antibodies to desmoplakins have been associated with paraneoplastic
      pemphigus. Here, we report a case of non-neoplastic pemphigus foliaceous with
      antibodies to desmoplakins. OBSERVATION: A 61-year-old woman with pemphigus
      foliaceous by clinical, histological and immunofluorescent criteria was found to
      have circulating antibodies to 250 and 215 kDa antigens identified as desmoplakin
      I and II by immunoblotting and immunoprecipitation. The patient had no evidence
      of cancer during a follow-up period of 3 years. CONCLUSION: Although antibodies
      to desmoplakin I and II have previously been associated with paraneoplastic
      pemphigus, their occasional finding in erythema multiforme and bullous pemphigoid
      indicates that they can also occur in non-neoplastic pemphigus.

PMID- 9784046
TI  - Depot sulfonamid associated linear IgA bullous dermatosis with erythema
      multiforme-like clinical features.
AB  - A case of erythema multiforme-like reaction, following therapy with
      sulfadimethoxynum is reported in a 19-year-old male patient. Histological
      examination demonstrated a subepidermal bulla and direct immunofluorescence
      revealed linear deposition of IgA at the dermoepidermal junction. These
      observations illustrate that linear IgA bullous dermatosis can mimic the clinical
      features of erythema multiforme and suggest the possibility of drug-induced
      pathogenesis.

PMID- 9784048
TI  - Incontinentia pigmenti: variable disease expression within an affected family.
AB  - We report a florid case of incontinentia pigmenti in a neonate in which linear
      vesiculobullous, verrucous and pigmented lesions were present simultaneously at
      birth. Histology of a vesiculobullous lesion showed vesiculation with numerous
      eosinophils in the epidermis, and a sparse infiltrate in the dermis with
      pigmentary incontinence. The mother of our patient described a streaky linear
      rash on her legs during her own childhood which resolved spontaneously, in
      addition to partial anodontia, suggesting that she too has the disease, although
      previously undiagnosed. This emphasises the variable disease expression and the
      importance of recognising this condition so that patients can be followed up with
      regard to complications, and genetic counselling can be offered. The issue of
      prenatal diagnosis is discussed.

PMID- 9784049
TI  - Efficacy of cyclosporine plus etretinate in the treatment of erythrodermic
      psoriasis (three case reports).
AB  - BACKGROUND: Association of different treatments are often used in erythrodermic
      psoriasis in order to increase the effectiveness and decrease the incidence of
      side effects due to single drugs. MATERIALS AND METHODS: Three in-patients
      affected by erythrodermic psoriasis, not responding to cyclosporine, (two
      patients) and etretinate, (one patient), were treated with the association
      cyclosporine plus etretinate. RESULTS: Clinical response was prompt to the
      combined therapy. The two drugs were tapering off gradually over 6 months; the
      patients maintained the remission for prolonged period. CONCLUSIONS: Combined
      cyclosporine-etretinate therapy may be considered as an effective and well
      tolerated treatment of erythrodermic psoriasis in patients not responding to
      monotherapy regimen.

PMID- 9784050
TI  - Erythrokeratoderma variabilis: case report and review of the literature.
AB  - We report two patients, mother and daughter, with Erythrokeratoderma variabilis
      (EV). This rare genodermatosis is characterized by the presence of two
      components: migratory erythema and fixed hyperkeratosis. Our patients experienced
      symptomatic relief of pruritus associated with erythema with the use of an oral,
      low-sedating H1-antihistamine. Revision of the literature in order to allocate
      the frequency of pruritus in EV and discussion of this association will follow.

PMID- 9784052
TI  - Targetoid hemosiderotic hemangioma.

PMID- 9784053
TI  - Chronic eczematous reaction to red tattoo.

PMID- 9784051
TI  - Endomysium and antigliadin antibodies in dermatitis herpetiformis and other
      bullous diseases.

PMID- 9784054
TI  - Short-term treatment of pityrosporum folliculitis: a double blind placebo
      controlled study.

PMID- 9784055
TI  - Inflammatory tinea capitis (Kerion) caused by Trichophyton rubrum.

PMID- 9784056
TI  - Therapeutic effect of essential phospholipids on functional sexual disorders in
      males.

PMID- 9784057
TI  - Shedding of the nails due to chemotherapy (onychomadesis)

PMID- 9784059
TI  - The 8th annual meeting of the Association for Psychocutaneous Medicine of North
      America.

PMID- 9784058
TI  - Unusual isotopic responses on healed herpes zoster lesions--report on two cases.

PMID- 9784061
TI  - Identification, expression, and characterization of the pseudorabies virus DNA
      binding protein gene and gene product.
AB  - The pseudorabies virus (PRV) gene encoding a DNA-binding protein (DBP) was first
      identified in this study. The DBP gene has an open reading frame of 3531
      nucleotides, capable of coding a 1177-amino-acid polypeptide of 125 kDa. The
      deduced DBP exhibits a conserved zinc-binding motif and a conserved DNA-binding
      region, suggesting the similar DNA-binding mechanism occurs among
      alphaherpesviral DBP homologs. To further identify the biochemical properties of
      PRV DBP, this protein was expressed in Escherichia coli by using a pET expression
      vector and purified to homogeneity. The PRV DBP binds cooperatively and
      preferentially to single-stranded DNA with no significant base preference, judged
      by agarose gel electrophoresis and competitive nitrocellulose filter binding
      assays. Taken together, these results suggest that PRV DBP may play an important
      role in PRV DNA replication by binding cooperatively and nonspecifically to
      single-stranded DNA that is formed during the replication origin unwinding and
      replication fork movement.

PMID- 9784060
TI  - UV protective clothing in Europe: recommendation of a European working party.

PMID- 9784062
TI  - Protective immunity against equine herpesvirus type-1 (EHV-1) infection in mice
      induced by recombinant EHV-1 gD.
AB  - The ability of recombinant preparations of equine herpesvirus type 1 (EHV-1)
      glycoprotein D (gD) to elicit specific antibody and T lymphocyte responses in the
      BALB/c mouse model of respiratory infection was investigated. Recombinant gD
      (rgD) expressed as a glutathione-S-transferase (GST) fusion protein in
      Escherichia coli elicited both high titer neutralizing antibody (nAb) and CD4 T
      cell proliferative responses following subcutaneous or intranasal immunization,
      but elicited only a weak antibody response after intraperitoneal immunization.
      Protection against respiratory tract infection with pathogenic EHV-1 RacL11 was
      observed in mice immunized subcutaneously with GST-gD. Furthermore, the degree of
      protection correlated to the titer of nAb and the T cell response observed.
      Finally, GST-gD was more effective in protecting against respiratory RacL11
      infection if delivered intranasally. These results confirm that gD plays an
      important role in eliciting the protective immune response against EHV-1
      infection, and indicate that subunit vaccines containing preparations of gD may
      be very effective if delivered directly to the upper respiratory tract.

PMID- 9784063
TI  - Evidence for a bidirectional promoter complex within the X gene of woodchuck
      hepatitis virus.
AB  - The genetic organization of hepadnaviruses is unusual in that all cis-acting
      regulatory sequences are located within genes. Thus, in the mammalian
      hepadnavirus genome, the presurface, surface, and X transcript promoters reside
      within the polymerase gene while the pregenome transcript promoter is located
      within the X gene. In this study we have identified two additional promoters
      within the woodchuck hepatitis virus (WHV) X gene that stimulate production of
      transcripts in vitro. First, we cloned regions of the WHV X gene into a
      promoterless expression vector (pGL2) to examine their ability to promote
      expression of firefly luciferase and mapped a previously unidentified promoter to
      positions 1475-1625 of the WHV8 genome. Deletion analysis revealed that the
      essential domain of this promoter, termed the ORF5/deltaX transcript promoter,
      mapped to nucleotides 1525-1625. Analysis revealed that this transcript initiated
      at nucleotide 1572 in both human (HuH-7) and woodchuck (WLC-3) hepatoma cell
      lines. Consistent with this finding, DNA footprinting analysis revealed
      protection of nucleotides 1567-1578 on the positive strand of the WHV8 genome.
      The function of this transcript in vivo is unclear, however, it may be used to
      produce a truncated form of the X protein that initiates at an AUG codon at
      position 1743-1745 on the WHV8 genome. Next, a second promoter was identified at
      positions 1625-1975 that was responsible for production of an antisense
      transcript. The activity of this promoter was comparable to that of the
      previously characterized surface transcript promoter of WHV in the absence of an
      enhancer. The antisense transcript promoter resides immediately upstream of open
      reading frame (ORF) 6, a previously identified ORF on the strand opposite of the
      known WHV protein-encoding sequences, that is thought to represent a vestigial
      gene. Analysis indicates that the antisense transcript had multiple start sites:
      nucleotides 1683 and 1762 on the WHV8 genome when assayed in HuH-7 cells, and
      nucleotide 1786 when assayed in WLC-3 cells. These data are consistent with
      footprinting analysis of supercoiled WHV DNA that revealed that the regions
      encompassing nucleotides 1696-1685, 1781-1766, and 1801-1787 on the negative
      sense DNA strand were protected from nuclease degradation. It is possible that
      such a transcript was once used in protein expression in an ancestral virus and
      may now be used for genetic control of WHV replication and/or gene expression.
      Overall, these data are consistent with the presence of a bidirectional promoter
      complex within the WHV X gene.

PMID- 9784064
TI  - A comparison between permissive and restricted infections with Aleutian mink
      disease parvovirus (ADV): characterization of the viral protein composition at
      nuclear sites of virus replication.
AB  - We used three-color fluorescent labeling and confocal microscopy to compare the
      permissive and the antibody-mediated, restricted replication of Aleutian mink
      disease parvovirus (ADV). In both permissive (CRFK cells) and restricted (K562
      cells) situations, both ADV non-structural proteins (NS1 and NS2) concentrated at
      focal sites in the nucleus, which also contained viral DNA. Bromodeoxyuridine
      labeling demonstrated that these sites also supported active ADV single-strand
      DNA synthesis, indicating that they were replication compartments. ADV capsid
      proteins were located in intranuclear shells surrounding the replication
      compartments. At later time points, NS2 was readily detected in the cytoplasm of
      permissively infected CRFK cells, whereas the cytoplasmic presence of NS2 was
      much less pronounced in the K562 cells. These results showed that both permissive
      and restricted ADV replication are associated with a tight nuclear
      subcompartmentalization of viral products. Furthermore, differences between the
      permissive and restricted virus-cell interactions were noted, suggesting that
      there may be a morphological basis for examining the outcome of ADV infection.

PMID- 9784065
TI  - Analysis of genomic rearrangement and subsequent gene deletion of the attenuated
      Orf virus strain D1701.
AB  - The orf virus (OV) strain D1701 belongs to the genetically heterogenous
      parapoxvirus (PPV) genus of the family Poxviridae. The attenuated OV D1701 has
      been licensed as a live vaccine against contagious ecthyma in sheep. Detailed
      knowledge on the genetic structure and organization of this PPV vaccine strain is
      an important prerequisite to reveal possible genetic mechanisms of PPV
      attenuation. The present study demonstrates a genomic map of the approximately
      158 kbp DNA of OV D1701 established by hybridization studies of cloned
      restriction fragments covering the complete viral genome. The results show an
      enlargement of the inverted terminal repeats (ITR) to up to 18 kbp due to
      recombination between nonhomologous sequences during cell culture adaptation. DNA
      sequencing of the region adjacent to the ITR junction revealed the absence of one
      open reading frame designated E2L. In contrast to a transposition-deletion
      variant of the New Zealand OV strain NZ2 (Fleming et al., 1995) the two genes E3L
      (a homologue of dUTPase) and G1L neighbouring E2L are retained in OV D1701. DNA
      and RNA analyses proved the presence of E2L gene in wild-type OV isolated
      directly from scab material. The data presented indicate that the E2L gene is
      nonessential for virus replication in vitro and in vivo, and may represent one
      important viral gene in determining virulence and pathogenesis of OV.

PMID- 9784066
TI  - Nucleotide sequence and phylogenetic analysis of the medium (M) genomic RNA
      segments of three hantaviruses isolated in China.
AB  - The medium (M) genome segment of hantaviruses (family Bunyaviridae) encodes the
      two virion glycoproteins. G1 and G2, as a precursor protein in the complementary
      sense RNA. We determined the nucleotide sequences of the M genome segments of
      three Chinese hantavirus isolates, a Hantaan-type (HTN) virus designated A9 and
      two Seoul-type (SEO) viruses designated L99 and HB55, and compared them to those
      of other HTN or SEO viruses isolated in Eastern Asia. The M segment of A9 is 3616
      nucleotides in length and shows 99.5% identity at the nucleotide level and 99.1%
      identity at the amino acid level to that of the Chinese HTN isolate HV114. The M
      segments of L99 and HB55 are 3652 nucleotides in length, one nucleotide longer
      than the M segments of other sequenced SEO isolates such as SEO 80-39, SR-11, and
      Biken-1. The Chinese SEO isolates showed 95% nucleotide sequence identity and 99%
      amino acid sequence identity to SEO 80-39. We also sequenced a 736 nucleotides
      region of the M genome segment of another Chinese SEO isolate, R22, which
      revealed errors in the published data. Phylogenetic analysis of the available
      sequences indicated that both the Chinese HTN- and SEO-type viruses form lineages
      distinct from those of the isolates from other parts of Eastern Asia.

PMID- 9784068
TI  - Characterization of the nucleoside triphosphate phosphohydrolase I gene from the
      Choristoneura fumiferana entomopoxvirus.
AB  - Poxviruses carry the enzyme, nucleoside triphosphate phosphohydrolase I (NPH I),
      required for early viral transcription in the cytoplasm of infected cells. The
      gene (nph I) encoding this enzyme from Choristoneura fumiferana entomopoxvirus
      (CfEPV) has been located in the viral genome, cloned and characterized. It has an
      open reading frame of 1941 nucleotides, potentially encoding a protein with a
      predicted molecular mass of 76.04 kDa and a pI of 8.83. It has a TAAATG motif
      where the trinucleotide ATG represents the translational start signal an AT-rich
      (88%) sequence and an early transcription termination signal (TTTTTAT) upstream
      of the ATG codon. Northern blot analysis of mRNA from infected larvae showed that
      a single 4.0 kb transcript which appeared late at day 20 post infection (p.i.)
      and its transcription continued till day 37 p.i.. Primer extension experiments
      suggested that the main transcripts started at 15 bases upstream of AUG codon.
      NPH I homologues have been found in the genomes of other entomopoxviruses and
      vertebrate poxviruses. Alignment of their amino acid sequences suggested three
      conserved domains, two of which are considered as ATP binding domains. The most
      similar homologue is from the closely related entomopoxvirus. Choristoneura
      biennis EPV (CbEPV) where 98.2% of nucleotide and 97.2% of amino acid identities
      are observed, respectively. A single nucleotide difference in CfEPV nph I was
      sufficient to distinguish it from CbEPV by PCR amplification and digestion with a
      restriction enzyme.

PMID- 9784067
TI  - Identification and characterization of the glycoprotein E and I genes of canine
      herpesvirus.
AB  - We have determined the sequence of the gE and gI genes of canine herpesvirus
      (CHV), DFD-6 strain. The gE ORF codes for a 522 a.a. polypeptide with a signal
      sequence at the amino-terminus and a trans-membrane domain at the carboxy
      terminus. The gI ORF codes for a 259 a.a. polypeptide with a signal sequence but
      no trans-membrane domain. Comparison with another line of CHV indicated that the
      DFD-6 gI gene underwent a frame-shift mutation which caused the loss of the trans
      membrane domain. Antibodies against the gE and gI polypeptides detected a 94 kDa
      gE and a broad band of gI (55-62 kDa) in DFD-6 infected cells, respectively. The
      precursor of DFD-6 gE is modified to the mature form by N-linked glycosylation
      only in the presence of gI. Together with the fact that the gI- mutant of DFD-6
      produced smaller plaques, it is suggested that the truncated DFD-6 gI is
      functional. The precursor of DFD-6 gI is modified to the mature form by N-linked
      glycosylation only in the presence of gE.

PMID- 9784069
TI  - The UL112/113 gene products of human cytomegalovirus which colocalize with viral
      DNA in infected cell nuclei are related to efficient viral DNA replication.
AB  - The UL112/113 gene products of human cytomegalovirus (HCMV) were shown by
      transient complementation ori Lyt-dependent DNA replication assay to be early
      viral proteins required for efficient viral DNA synthesis. By immunofluorescence
      analysis followed by fluorescence in situ hybridization, we showed that UL112/113
      gene products of HCMV are colocalized with viral DNA prior to and during viral
      DNA replication in infected cell nuclei. We have used an anti-sense RNA approach
      for functional analysis of the UL112/113 gene in HCMV. The astrocytoma cell line
      U373-MG was used for permanent expression of the anti-sense UL112/113 gene.
      Expression of the anti-sense RNA in this cell line significantly blocked
      expression of UL112/113 gene products and viral DNA replication, indicating that
      the UL112/113 gene products are related to efficient viral DNA replication.

PMID- 9784071
TI  - Progressive-ratio schedules of drug delivery in the analysis of drug self
      administration: a review.
AB  - Drugs, like other reinforcers, can vary in their relative abilities to support
      operant responding. Considerable research has been designed to obtain useful
      measures of a given drug's or dose's "reinforcing efficacy" and to identify the
      ways in which a variety of behavioral and pharmacological variables impact these
      measures. Progressive-ratio schedules of drug delivery generate an index of a
      drug's or dose's reinforcing efficacy (the breaking point) and are being used
      increasingly as tools in the analysis of drug self-administration. Progressive
      ratio schedules of drug delivery have been used to characterize the effects of
      pretreatment drugs, lesions, drug deprivation, physical dependence, and repeated
      non-contingent drug exposure on breaking points. Behavioral factors, including
      food restriction and electric shock, and organismic factors, including gender and
      strain, have also been investigated using progressive-ratio schedules of drug
      delivery. To the extent that breaking points provide an index of reinforcing
      efficacy, these studies demonstrate that a wide range of variables can influence
      the reinforcing efficacy of self-administered drugs. The objectives of this
      review are to critique existing research themes, outline potential limitations of
      progressive-ratio procedures, and to suggest potentially fruitful uses of these
      procedures in future research.

PMID- 9784070
TI  - A specific T-cell subset with CD4+/CD38- markers derived from HIV-1 carriers
      induces apoptosis in healthy donor-derived T-lymphocytes.
AB  - Apoptosis is an important mechanism of human immunodeficiency virus type 1 (HIV
      1)-induced T-cell depletion. Our recent findings revealed mitogenic stimulation
      dependent apoptosis induction in healthy donor-derived peripheral blood T
      lymphocytes after adsorption with defective HIV-1 particles through acquirement
      by a subset of CD4+/CD38- cells of specific killer function. Based on these in
      vitro observations, we have extended the significance of this killing activity of
      CD4+/CD38- cells directly derived from HIV-1 carriers. The CD4+/CD38- cells from
      HIV-1-positive individuals showed significantly higher cell-killing activities
      than those from HIV-1-negative donors by co-culture with allogeneic resting T
      cells after mitogenic stimulation. Furthermore, most of the samples induced
      apoptosis in a Fas-dependent manner. Thus, it is suggested that HIV-1 infection
      related apoptosis is triggered by inappropriate activation of a certain resting T
      cell subset, presumably due to adsorption with HIV-1 particles.

PMID- 9784072
TI  - Comparative effects of novel 5-HT1A receptor ligands, LY293284, LY315712 and
      LY297996, on plus-maze anxiety in mice.
AB  - In contrast to the variable efficacy of 5-HT1A receptor full and partial agonists
      in animal models of anxiety, recent findings in our laboratory have revealed
      remarkably consistent anxiolytic-like effects for 5-HT1A receptor antagonists in
      the murine elevated plus-maze paradigm. In the present study, ethological
      techniques were used directly to compare the plus-maze profiles of three novel
      ligands varying in intrinsic efficacy at 5-HT1A receptors: LY293284 (full
      agonist; 0.01-0.3 mg/kg), LY315712 (partial agonist; 0.3-3.0 mg/kg), and LY297996
      (antagonist; 0.03-10.0 mg/kg). At the lowest dose tested, LY293284 tended to
      enhance several indices of anxiety, whereas higher doses suppressed all active
      behaviours. Although few behavioural effects were observed with LY315712 under
      present test conditions, a selective reduction in risk assessment was apparent at
      1.0-3.0 mg/kg. In contrast to these profiles, LY297996 (3.0-10.0 mg/kg) produced
      robust anxiolytic-like effects on conventional and ethological parameters but,
      importantly, did not alter general activity levels. These results provide further
      support for the anxiolytic potential of 5-HT1A receptor antagonists and are
      discussed in relation to possible factors underlying inter-laboratory variation
      in the effects of these agents in animal models of anxiety.

PMID- 9784073
TI  - Physical dependence increases the relative reinforcing effects of caffeine versus
      placebo.
AB  - Using a within-subject cross-over design, this study examined the role of
      physical dependence in caffeine reinforcement by experimentally manipulating
      physical dependence. Each subject was exposed to two chronic drug phases (300
      mg/70 kg/day caffeine and placebo) for 9-12 days, with order of phases
      counterbalanced across subjects. On 2 separate days immediately following each of
      the chronic drug exposures, subjects received acute doses of either caffeine (300
      mg/70 kg) or placebo in counterbalanced order. The reinforcing effects of these
      drugs were then determined by using a multiple-choice procedure in which subjects
      made a series of discrete choices between receiving varying amounts of money or
      receiving the drug again, and a choice between the two drugs. To ensure that
      subjects completed the form carefully, following exposure to both of the acute
      drug administrations, one of the subject's previous choices from the multiple
      choice form was randomly selected and the consequence of that choice was
      implemented. When subjects were maintained on chronic caffeine, they were willing
      to forfeit significantly more money and showed significant increases in typical
      withdrawal symptoms (e.g. fatigue, mood disturbance) after receiving placebo as
      compared to the other three conditions. When subjects were maintained on chronic
      caffeine, they also chose to receive caffeine over placebo twice as often than
      when they were maintained on chronic placebo. These findings provide the
      strongest evidence to date indicating that caffeine physical dependence increases
      the relative reinforcing effects of caffeine versus placebo.

PMID- 9784075
TI  - Effects of isolation-rearing on voluntary consumption of ethanol, sucrose and
      saccharin solutions in Fawn Hooded and Wistar rats.
AB  - These experiments examined the hypothesis that isolation-rearing and strain
      influence hedonic mechanisms. In experiment 1, voluntary consumption of ethanol
      and water was monitored in the home cage of Fawn Hooded (FH) and Wistar rats. FH
      rats were found to consume more ethanol at low concentrations than Wistar rats,
      independent of rearing condition, and isolation-reared rats were found to consume
      more of high ethanol concentrations, independent of strain. In experiment 2,
      isolation-reared rats were found to consume more sucrose, independent of
      concentration, than socially reared rats. In experiment 3, Fawn Hooded rats were
      found to be more sensitive to low concentration solutions of saccharin, and to
      consume less of the high concentration solutions, while isolation-rearing was
      found to enhance consumption of high concentrations. Thus, hedonic processes are
      independently modulated by strain and rearing conditions, although the effects of
      isolation-rearing appear to be exacerbated in Fawn Hooded rats.

PMID- 9784074
TI  - Effects of isolation-rearing on locomotion, anxiety and responses to ethanol in
      Fawn Hooded and Wistar rats.
AB  - Voluntary ethanol (EtOH) consumption is increased by isolation-rearing in several
      rat strains. The following experiments examined the effects of isolation-rearing
      on basal and ethanol-stimulated behavior in Fawn Hooded rats, an alcohol
      preferring rat strain, compared to Wistar rats. Locomotor activity and anxiety
      were examined under both conditions. Basal locomotor activity was higher in
      isolated subjects of both strains in low light conditions, but under bright light
      conditions, this difference was only observed in Wistar rats. Locomotor stimulant
      effects of EtOH were only observed in isolation-reared rats. In the elevated plus
      maze, Fawn Hooded rats were more anxious than Wistar rats under low light
      conditions, but under bright light conditions, Wistar socials were less anxious
      than all of the other groups. Administration of 1.5 mg/kg EtOH produced an
      anxiolytic response in the elevated plus maze under bright light conditions in
      Fawn Hooded rats, but to a lesser degree Wistar rats, particularly Wistar
      isolates. In conclusion, although both strain and isolation-rearing had effects
      on locomotion and anxiety as well as the stimulatory and anxiolytic effects of
      EtOH, these effects appeared to be independent.

PMID- 9784076
TI  - The effect of sucrose on acute tobacco withdrawal in women.
AB  - Carbohydrate consumption is thought to attenuate symptoms of tobacco withdrawal,
      but direct evidence for this idea does not exist. Using a 2 x 2 (smoking/smoking
      deprived x sucrose/placebo) factorial design, we examined in 67 women whether
      sucrose would decrease acute withdrawal symptoms observed after 12 h of tobacco
      abstinence. Sucrose decreased tobacco abstinence-induced drowsiness and anxiety
      and preference for foods high in carbohydrate and fat content. Sucrose, however,
      had no effect on several other acute withdrawal symptoms, including restlessness,
      irritability and concentration difficulties. These results provide modest support
      for the idea that increased carbohydrate intake during tobacco withdrawal reduces
      certain withdrawal symptoms even after only 12 h of abstinence.

PMID- 9784077
TI  - Involvement of the ventral tegmental area opiate receptors in self-stimulation
      elicited from the ventral pallidum.
AB  - Enkephalinergic and dopaminergic mechanisms have been implicated in the
      electrical self-stimulation (SS) behavior. The present set of experiments
      investigated the role of opioid receptors within DA-innervated brain regions
      (nucleus accumbens and ventral tegmental area) in the ventral pallidum self
      stimulation (VP-SS). Forty-one rats used in this study were implanted with a
      monopolar moveable stimulating electrode in the VP. A rate-frequency curve-shift
      method was applied to determine the reward (threshold) and motor functions
      (asymptotic rate) of self stimulation elicited from the VP. One group received
      systemic treatment of graded doses (vehicle; 1.25; 2.50 mg/kg) of morphine
      injected IP, 60 min before behavioural testing. The results showed a tendency for
      increased threshold of VP-SS and of the asymptotic rate of responding. Three
      additional groups were implanted with guide cannulae in the nucleus accumbens
      (NAC), the ventral tegmental area (VTA) or dorsally to the VTA and received
      microinjections of morphine (vehicle: 1.25; 2.50; 5.0; 10.0 microg/0.5 microl per
      side). Central injections of morphine higher than 1.25 microg/side into the VTA
      were associated with a significant reduction in VP-SS thresholds, indicating a
      potentiative effect on reward. Microinjections of morphine either into the NAC or
      into the dorsal tegmentum did not produce significant alterations on thresholds
      or responding of VP-SS. In order to investigate the extent to which the VTA-NAC
      dopamine projection was involved in the SS behavior elicited from the ventral
      pallidum, we tested SS in animals that suffered NAC 6-hydroxydopamine (6-OHDA)
      lesions. Rats suffering NAC dopamine depletion along with their corresponding
      controls showed similar levels of thresholds and responding to the ones exhibited
      prior to the lesion, revealing that NAC dopamine is not necessary to maintain VP
      SS. The results suggest that stimulation of opioid receptor in the VTA increases
      the rewarding efficacy of VP-SS. This effect might be due to the modulation of
      VTA-DA neurons projecting to the VP rather than to the NAC.

PMID- 9784078
TI  - The effects of black tea and other beverages on aspects of cognition and
      psychomotor performance.
AB  - Nineteen healthy volunteers ingested 400 ml black tea, coffee, caffeinated water,
      decaffeinated tea or plain water on three occasions through the day (0900, 1400
      and 1900 hours). A 2 x 2 factorial design with caffeine (0, 100 mg) and beverage
      type (water, tea) was employed, with coffee (100 mg caffeine) as a positive
      internal control, based on a five-way crossover. A psychometric test battery
      comprising critical flicker fusion (CFF), choice reaction time (CRT), short-term
      memory (STM) and subjective sedation (LARS) was performed at regular intervals
      throughout the day, and intensively so immediately following each beverage.
      Consumption of tea compared to water was associated with transient improvements
      in performance (CFF) within 10 min of ingestion and was not affected by the time
      of day. Caffeine ingestion was associated with a rapid (10 min) and persistent
      reduction in subjective sedation values (LARS), again independent of time of day,
      but did not acutely alter CFF threshold. Over the whole day, consumption of tea
      rather than water, and of caffeinated compared to decaffeinated beverages,
      largely prevented the steady decline in alertness (LARS) and cognitive capacity
      observed with water ingestion. The effects of tea and coffee were similar on all
      measures, except that tea consumption was associated with less variation in CFF
      over the whole day. No significant treatment effects were apparent in the data
      for the STM. Tea ingestion is associated with rapid increases in alertness and
      information processing capacity and tea drinking throughout the day largely
      prevents the diurnal pattern of performance decrements found with the placebo (no
      caffeine) condition. It appears that the effects of tea and coffee were not
      entirely due to caffeine per se; other factors either intrinsic to the beverage
      (e.g. sensory attributes or the presence of other biologically active substances)
      or of a psychological nature (e.g. expectancy) are likely to play a significant
      role in mediating the responses observed in this study.

PMID- 9784079
TI  - Chronic dietary inositol enhances locomotor activity and brain inositol levels in
      rats.
AB  - myo-Inositol has been found to be clinically effective in depression, obsessive
      compulsive disorder (OCD) and panic disorder when given chronically per os. The
      present study examined the effects of chronic dietary inositol in rats on
      locomotor behaviour. Regional brain levels of inositol were analyzed by gas
      chromatography. Chronic dietary inositol significantly enhanced locomotion and
      rearing in rats and elevated inositol levels by 36% in the cortex and 27% in
      hippocampus. No differences in inositol levels were found in the striatum or
      cerebellum. The stimulatory effects of inositol may be related to its effects as
      an atypical antidepressant in depressed patients.

PMID- 9784080
TI  - 5-Hydroxytryptamine receptor function in humans is reduced by acute
      administration of hydrocortisone.
AB  - 5-Hydroxytryptamine1A (5-HT1A) receptors have been shown to be suppressed by
      corticosteroid hormones in a variety of animal experimental paradigms. It has
      been suggested that this effect may be central to the pathophysiology of severe
      clinical depressive illness, a condition in which 5-HT1A receptor function is
      reduced and corticosteroid hormones are elevated. We report the effects of acute
      administration of hydrocortisone in normal volunteers on a neuroendocrine model
      of 5-HT1A receptor function. Fifteen healthy male volunteers took part in a
      random order, double blind, placebo controlled study, in which 100 mg
      hydrocortisone or placebo was administered 11 h before infusion of L-tryptophan
      (L-TRP). Pre-treatment with hydrocortisone significantly reduced the growth
      hormone (GH), but not the prolactin (PRL) response to the infusion. These data
      are consistent with the view that acute administration of corticosteroid hormones
      significantly impairs 5-HT1A receptor mediated function in healthy human
      volunteers and are in line with animal studies of the effects of corticosteroid
      hormones on 5-HT1A receptors. We propose that this finding is relevant to the
      pathophysiological processes which cause severe depressive illness.

PMID- 9784081
TI  - Repeated heroin administration increases extracellular opioid peptide-like
      immunoreactivity in the globus pallidus/ventral pallidum of freely moving rats.
AB  - Microdialysis was used to investigate the effects of heroin administration on
      extracellular opioid peptide levels in the globus pallidus/ventral pallidum of
      freely moving rats. Two injections of heroin (0.6 mg/ kg i.p.) were given 3 h
      apart. The first injection had no significant effect on opioid peptide levels,
      but the second injection produced a transient yet significant increase (+268%) in
      opioid peptide-like immunoreactivity in pallidal dialysates, peaking 1 h after
      injection. This effect was blocked by administration of naloxone (3 mg/kg i.p.)
      prior to the second injection. The implications of these data are discussed with
      regards to the role of the endogenous opioid peptide system in opiate reward.

PMID- 9784082
TI  - Ca2+ dependency of serotonin and dopamine release from CNS slices of chronically
      isolated rats.
AB  - Much evidence points to a significant involvement of the classical
      neurotransmitters 5-HT and DA in affective disorders with possible changes in
      different structures of the CNS and also at different levels of the signal
      transduction chain, i.e., receptor, synthesis, uptake or release. We have used
      chronic isolated housing as an animal model of depression. These isolated rats
      enabled the study of KCl-induced release of 5-HT and DA from nucleus accumbens,
      prefrontal cortex and hippocampal slices. The following questions were addressed:
      first, if there is a change in the depolarization dependent release of DA and 5
      HT from these CNS structures, and second, if the release is through the classical
      exocytotic mechanism. A significant increase in KCl stimulated release of 5-HT
      was observed in chronically isolated animals when compared to controls. 5-HT
      release was completely abolished from controls or isolated animals, when slices
      were incubated with Krebs containing zero Ca2+/10 mM Mg2+, the inorganic Ca2+
      channel blockers, Cd2+ or Ni2+ and the calmodulin inhibitor, trifluoperazine. The
      organic Ca2+ channel blockers nifedipine and D-600 were less effective in
      inhibiting the stimulated 5-HT release. KCl stimulated DA release was only
      significantly increased from hippocampus slices, of isolated, but not control
      animals. This release was also highly Ca2+-dependent. The basal release of DA and
      5-HT was similar in control and isolated animals and was not affected by the Ca2+
      channel antagonists. The results suggest that extracellular Ca2+-dependent
      release of 5-HT and, to a lesser degree, of DA, is increased in this chronic
      animal model of depression in several CNS structures.

PMID- 9784083
TI  - Ecstasy (MDMA) effects upon mood and cognition: before, during and after a
      Saturday night dance.
AB  - Three groups of young people (aged 19-30 years) were compared: 15 regular ecstasy
      users who had taken MDMA (3,4-methylenedioxymethamphetamine) on ten or more
      occasions; 15 novice ecstasy users who had taken MDMA on fewer than ten previous
      occasions; and 15 controls who had never taken MDMA. Each subject completed a
      cognitive test and mood scale battery four times: an initial drug-free baseline,
      at a Saturday night dance/club (on-drug), then 2 days later, and 7 days later. On
      the Saturday night, regular ecstasy users took an average of 1.80 MDMA tablets,
      novice users took 1.45 MDMA tablets, while controls mostly drank alcohol. The
      consumption of cannabis and cocaine at the club was similar across groups. All
      three groups reported positive moods at the dance club (on-drug), although there
      were borderline trends (P < 0.10) for less sadness/depression in the MDMA
      subgroups. However 2 days afterwards, the ecstasy users felt significantly more
      depressed, abnormal, unsociable, unpleasant, and less good tempered, than the
      controls. Cognitive performance on both tasks (verbal recall, visual scanning)
      was significantly reduced on-MDMA. Memory recall was also significantly impaired
      in drug-free MDMA users, with regular ecstasy users displaying the worst memory
      scores at every test session. This agrees with previous findings of memory
      impairments in drug-free ecstasy users. Animal data have shown that MDMA can
      generate long-term serotonergic neurodegeneration in various brain areas,
      including the hippocampus. The cognitive deficits in drug-free recreational
      ecstasy users, suggest that MDMA may also be neurotoxic in humans.

PMID- 9784084
TI  - Effect of itraconazole on the single oral dose pharmacokinetics and
      pharmacodynamics of alprazolam.
AB  - To assess the effect of itraconazole, a potent inhibitor of cytochrome P450 (CYP)
      3A4, on the single oral dose pharmacokinetics and pharmacodynamics of alprazolam,
      the study was conducted in a double-blind randomized crossover manner with two
      phases of treatment with itraconazole-placebo or placebo-itraconazole. Ten
      healthy male subjects receiving itraconazole 200 mg/day or matched placebo orally
      for 6 days took an oral 0.8 mg dose of alprazolam on day 4 of each treatment
      phase. Plasma concentration of alprazolam was measured up to 48 h after
      alprazolam dosing, together with the assessment of psychomotor function by the
      Digit Symbol Substitution Test, Visual Analog Scale and Udvalg for kliniske
      undersogelser side effect rating scale. Itraconazole significantly (P < 0.01)
      increased the area under the concentration-time curves from 0 h to infinity (252
      +/- 47 versus 671 +/- 205 ng h/ml), decreased the apparent oral clearance (0.89
      +/- 0.21 versus 0.35+/-0.10 ml/min per kg) and prolonged the elimination half
      life (15.7 +/- 4.1 versus 40.3 +/- 13.5 h) of alprazolam. The test performed
      during itraconazole treatment showed significantly depressed psychomotor
      function. It is suggested that itraconazole, a potent CYP3A4 inhibitor, increases
      plasma concentration of alprazolam via its inhibitory effects on alprazolam
      metabolism. Thus, this study supports previous studies suggesting that CYP3A4 is
      the major enzyme catalyzing the metabolism of alprazolam. Enhanced side effects
      of alprazolam by itraconazole coadministration were probably reflected by these
      pharmacokinetic changes.

PMID- 9784085
TI  - 18-Methoxycoronardine attenuates nicotine-induced dopamine release and nicotine
      preferences in rats.
AB  - Two studies were conducted to assess, in vivo, potential anti-nicotinic effects
      of the iboga alkaloid ibogaine and its synthetic congener 18-methoxycoronaridine
      (18-MC). As previously demonstrated for ibogaine, using microdialysis,
      pretreatment (19h beforehand) with 18-MC (40 mg/kg, i.p.) significantly
      attenuated nicotine-induced dopamine release in the nucleus accumbens of awake
      and freely moving rats. In an oral model of nicotine self-administration, both
      ibogaine and 18-MC decreased rats' preferences for nicotine for at least 24 h.
      Acutely, during the first hour after administration, ibogaine depressed
      responding for water as well as for nicotine; however, during this same time, 18
      MC reduced nicotine intake without affecting responding for water. The results
      suggest that 18-MC might be the prototype of a new treatment for smoking.

PMID- 9784086
TI  - Sensitization to the motor effects of contingent infusions of heroin but not of
      kappa agonist RU 51599.
AB  - It has been postulated that behavioral sensitization could reflect drug-induced
      changes that are central to the development of drug abuse; however, it is still
      unknown whether behavioral sensitization can arise during a "voluntary" and "self
      controlled" consumption of drugs and consequently play a role in drug abuse. For
      this reason, we studied the possible sensitization of motor activity during ten
      consecutive intravenous self-administration (SA) sessions of one of the most
      largely abused opiates the mu agonist heroin [30 microg/infusion (inf)]. We also
      studied in similar conditions the new kappa agonist RU 51599 (6.5, 20 and 100
      microg/inf). Heroin and RU 51599 were compared because both drugs are self
      administered by rodents, but the reinforcing properties of RU 51599 are very weak
      compared to those of heroin. At low ratio requirement rats developed SA of both
      heroin and RU 51599; however, a progressive increase in drug-induced locomotor
      activity over subsequent sessions was observed only for heroin but not for RU
      51599. Sensitization of the motor effects of heroin developed over a period of
      time during which the intake of the drug was constant. In conclusion,
      sensitization can develop during the voluntary consumption of an addictive drug
      such as heroin. These results are in line with the hypothesis that sensitization
      could play a role in the etiology of drug abuse.

PMID- 9784087
TI  - Antidepressant-like effect of Hypericum perforatum (St John's wort) on the sleep
      polysomnogram.
AB  - We studied the effect of two doses (0.9 mg and 1.8 mg) of Hypericum perforatum
      (St John's wort) on the sleep polysomnogram of healthy subjects using a placebo
      controlled, cross-over design. Both doses of hypericum significantly increased
      the latency to rapid eye movement (REM) sleep without producing any other effect
      on sleep architecture. Our data are consistent with the proposed clinical
      antidepressant efficacy of hypericum, and raise the possibility that its
      pharmacological mechanism of action may be similar to that of conventional
      antidepressant medication.

PMID- 9784088
TI  - Nicotine availability from Eclipse tobacco-heating cigarette.
AB  - A cigarette which heats rather than burns tobacco (Premier) was introduced in
      1988, but was unacceptable due to unpleasant taste and low nicotine intake. We
      examined availability of nicotine from a new version (Eclipse), in the same four
      subjects as our earlier Premier study. Average blood nicotine boosts of 23.7 and
      17.8 ng/ml were obtained from smoking a first and second Eclipse. This
      substantially exceeds intake from Premier (boost 13 ng/ml) and that obtained by
      heavy smokers from conventional brands (boost 12-15 ng/ml). Eclipse (or similar
      product) may be the best option for averting Peto's dire warnings of rising
      millions of annual smoking deaths in the 2020s, and its potential for large
      scale, long-term switching warrants further study.

PMID- 9784089
TI  - Tobacco use among U.S. racial/ethnic minority groups--African Americans, American
      Indians and Alaska Natives, Asian Americans and Pacific Islanders, Hispanics. A
      Report of the Surgeon General. Executive summary.

PMID- 9784090
TI  - Synthesis and modeling studies of a potent conformationally rigid muscarinic
      agonist: 1-azabicyclo[2.2.1]heptanespirofuranone.

PMID- 9784091
TI  - Acetylcholinesterase noncovalent inhibitors based on a polyamine backbone for
      potential use against Alzheimer's disease.

PMID- 9784092
TI  - Discovery of a novel, potent, and orally active nonpeptide antagonist of the
      human luteinizing hormone-releasing hormone (LHRH) receptor.

PMID- 9784093
TI  - 6-Amino-2-(4-fluorophenyl)-4-methoxy-3- (4-pyridyl)-1H-pyrrolo[2, 3-b]pyridine
      (RWJ 68354): a potent and selective p38 kinase inhibitor.

PMID- 9784094
TI  - Synthesis and evaluation of N-[11C]methylated analogues of epibatidine as tracers
      for positron emission tomographic studies of nicotinic acetylcholine receptors.
AB  - Four halogen-substituted analogues of N-methylepibatidine, a nicotinic
      acetylcholine receptor (nAChR) ligand, were synthesized. They were (+/-)-exo-N
      methyl-2-(2-halogeno-5-pyridyl)-7-azabicyclo[2. 2.1]heptanes, where halogeno = F
      (1a), Cl (2a), Br (3a), I (4a). (+/-)-N-Ethylepibatidine (2b) also was
      synthesized. The compounds 1a, 2a, 3a, and 4a and their corresponding normethyl
      analogues 1, 2, 3, and 4 inhibited the in vitro binding of [3H]epibatidine to
      nAChRs to a similar degree, with affinities in the 27-50 pM range. The binding
      affinity of N-ethylepibatidine (2b), however, was substantially lower. The N
      [11C]methyl derivatives of 1, 2, and 3 were synthesized from high-specific
      radioactivity [11C]methyl iodide using a high-temperature/high-pressure
      technique. The corresponding radiolabeled compounds [11C]1a, [11C]2a, and [11C]3a
      were administrated to mice intravenously. The pattern of regional distribution of
      the three tracers in the mouse brain following intravenous administration matched
      those of [3H]epibatidine, [3H]norchloroepibatidine, and (+/-)-exo-2-(2
      [18F]fluoro-5-pyridyl)-7-azabicyclo[2.2.1]heptane ([18F]FPH), which are highly
      specific nAChR probes. The initial brain uptake of the 11C analogues and the
      acute toxicity of the corresponding authentic nonlabeled compounds appeared to be
      related to their lipophilicity.

PMID- 9784095
TI  - Derivation of a pharmacophore model for anandamide using constrained
      conformational searching and comparative molecular field analysis.
AB  - Constrained molecular dynamics simulations on anandamide, together with a
      systematic distance comparison search, have revealed a specific low-energy
      conformer whose spatial disposition of the pharmacophoric elements closely
      matches that of HHC. This conformer enables near superposition of the following:
      (1) the oxygen of the carboxyamide and the phenolic hydroxyl group of HHC, (2)
      the hydroxyl group of the ethanol and the cyclohexyl hydroxyl group of HHC, (3)
      the alkyl tail and the lipophilic side chain of HHC, and (4) the polyolefin loop
      and the tricyclic ring structure of HHC. The close matching of common
      pharmacophoric elements of anandamide with HHC offers persuasive evidence of the
      biological relevance of this conformer. The proposed pharmacophore model was
      capable of discriminating between structurally related compounds exhibiting
      different pharmacological potency for the CB1 cannabinoid receptor, i.e.,
      anandamide and N-(2-hydroxyethyl)prostaglandinamide. Furthermore, a 3D-QSAR model
      was derived using CoMFA for a training set of 29 classical and nonclassical
      analogues which rationalized the binding affinity in terms of steric and
      electrostatic properties and, more importantly, which predicted the potency of
      anandamide in excellent agreement with experimental data. The ABC tricyclic HU
      210/HU-211 and ACD tricyclic CP55,243/CP55,244 enantiomeric pairs were employed
      as test compounds to validate the present CoMFA model. For each enantiomeric
      pair, the CoMFA-predicted log Ki values correctly identified that enantiomer
      exhibiting the higher affinity for the receptor.

PMID- 9784096
TI  - Novel cyclic compounds as potent phosphodiesterase 4 inhibitors.
AB  - The synthesis and biological activity of a novel series of 2, 2-disubstituted
      indan-1,3-dione-based PDE4 inhibitors are described. This structurally unique
      class of PDE4 inhibitors is markedly different from the known PDE4 inhibitors
      such as RP 73401 (2) and CDP 840 (3). Structure-activity relationship (SAR)
      studies led to the identification of inhibitors with nanomolar potency and oral
      activity in a murine endotoxemia model for TNF-alpha inhibition. Unlike other
      classical PDE4 inhibitors, several analogues were found to be nonemetic in a
      canine emesis model at intravenous doses of up to 3 mg/kg.

PMID- 9784097
TI  - In vitro and in vivo activities of oligodeoxynucleotide-based thrombin inhibitors
      containing neutral formacetal linkages.
AB  - A series of 15-mer oligodeoxynucleotide analogues were synthesized, and their
      thrombin inhibitory activities in vitro and in vivo were evaluated. These
      oligodeoxynucleotide analogues share the same sequence (GGTTGGTGTGGTTGG) but have
      one or more phosphodiester linkages replaced by a neutral formacetal group. The
      results obtained from monosubstitutions show that no single phosphodiester group
      is critical for the thrombin inhibitory activity, suggesting that the interaction
      between the oligodeoxynucleotide and thrombin is based on a multiple-site charge
      charge interaction. Analysis of the effects of different phosphodiester
      replacements indicates that the backside and left side of the chairlike structure
      formed by the molecule may be involved in binding with thrombin, presumably by
      having direct contacts with the anion-binding exosite of the enzyme. For the
      oligodeoxynucleotides containing two noncontiguous formacetal groups, the effect
      of the disubstitution is the sum of the effects obtained from the corresponding
      two monosubstitutions. Infusion of an oligodeoxynucleotide containing four
      formacetal groups into monkeys showed an increased in vivo anticoagulant effect
      and an extended in vivo half-life compared to the unmodified
      oligodeoxynucleotide.

PMID- 9784098
TI  - Axially chiral N-benzyl-N,7-dimethyl-5-phenyl-1, 7-naphthyridine-6-carboxamide
      derivatives as tachykinin NK1 receptor antagonists: determination of the absolute
      stereochemical requirements.
AB  - A potent and orally active NK1 antagonist, trans-N-[3, 5
      bis(trifluoromethyl)benzyl]-7,8-dihydro-N, 7-dimethyl-5-(4-methylphenyl)-8-oxo
      1,7-naphthyridine-6-carboxamide (1t), was shown to exist as a mixture of
      separable and stable (R)- and (S)-atropisomers (1t-A and 1t-B) originating from
      the restricted rotation around the -C(6)-C(=O)- bond; the antagonistic activities
      of 1t-A were ca. 6-13-fold higher than those of 1t-B. Analogues of 1t (3), which
      have (S)- and (R)-methyl groups at the benzylic methylene portion of 1t, were
      prepared and separated into the diastereomeric atropisomers, 3a-A, 3a-B and 3b-A,
      3b-B, in enantiomerically pure forms. Among the four isomers of 3, the (aR, S)
      enantiomer (3a-A) exhibited the most potent antagonistic activities with an IC50
      value of 0.80 nM (in vitro inhibition of [125I]BH-SP binding in human IM-9 cells)
      and ED50 values of 9.3 micrograms/kg (iv) and 67.7 micrograms/kg (po) (in vivo
      inhibition of capsaicin-induced plasma extravasation in guinea pig trachea),
      while the activity of the (aS,R)-enantiomer (3b-B) was the weakest with an IC50
      value of 620 nM. The structure-activity relationships in this series of
      antagonists indicate that the (R)-configuration at the axial bond and the
      stacking (or stacking-like) conformation between the two phenyl rings as shown in
      1t-A and 3a-A are essential for high-affinity binding and suggest that the amide
      moiety functions as a hydrogen bond acceptor in the interaction with the
      receptor.

PMID- 9784099
TI  - Design of benzamidine-type inhibitors of factor Xa.
AB  - A series of derivatives of rac-benzenesulfonyl-glycyl-phenylalanine or its ethyl
      ester with a combination of thioamido/amidino or amidino/amidino substituents in
      the benzene rings was synthesized as potential inhibitors of factor Xa (fXa).
      Among these, the racemic 4'-amidinobenzenesulfonyl-glycyl-4-amidinophenylalanine
      ethyl ester was found to exhibit the highest affinity for fXa despite the
      unfavored location of the amidino substituent in the para position. X-ray
      structural analysis of the trypsin complex with this bis-benzamidine compound
      revealed a retro-binding mode if compared to those of similar compounds, so far
      analyzed in complexes with trypsin or fXa. This noncanonical binding mode as well
      as its slow plasma clearance rates in rats, if compared to those of other
      benzamidine derivatives, suggests this compound as an interesting new lead
      structure for the design of fXa inhibitors.

PMID- 9784101
TI  - Quantitative structure-activity relationships of 2, 4-diamino-5-(2-X
      benzyl)pyrimidines versus bacterial and avian dihydrofolate reductase.
AB  - Quantitative structure-activity relationships (QSAR) have been formulated for a
      set of 15 2,4-diamino-5-(2-X-benzyl)pyrimidines versus dihydrofolate reductase
      from Lactobacillus casei and chicken liver. QSARs were also developed for
      comprehensive data sets containing mono-, di-, and trisubstituted benzyl
      derivatives. Particular emphasis was placed on the role played by ortho
      substituents in the overall binding process and subsequent inhibition of the
      catalytic process in both the prokaryotic and eucaryotic DHFRs. Comparisons
      between the two QSARs reveal subtle differences at specific positions which can
      be optimized to design more selective antibacterial agents.

PMID- 9784100
TI  - Metabolites of the angiotensin II antagonist tasosartan: the importance of a
      second acidic group.
AB  - Described in this paper is the synthesis and pharmacological activity of five
      metabolites of the angiotensin II antagonist tasosartan (1). Of particular
      interest is the effect of the additional acidic group of the enol metabolite (8)
      on activity. As suggested by the structural-activity relationship of other
      angiotensin II antagonist series, a second acidic group can improve receptor
      binding activity but decrease in vivo activity after oral dosing. The metabolic
      introduction of a second acidic group in tasosartan bypasses this problem and
      contributes to the excellent profile of the compound. A molecular modeling study
      provides a rationale for the role of the enol group of 8 in AT1 receptor binding.

PMID- 9784102
TI  - Design of new topoisomerase II inhibitors based upon a quinobenzoxazine self
      assembly model.
AB  - A new class of pyridobenzophenoxazine compounds has been developed as
      topoisomerase II inhibitors for anticancer chemotherapy. These compounds were
      designed based on a proposed model of a quinobenzoxazine self-assembly complex on
      DNA. They showed excellent inhibitory effects on several tumor cell lines with
      nanomolar IC50 values. Their cytotoxic potency correlates with their ability to
      unwind DNA and inhibit topoisomerase II.

PMID- 9784103
TI  - Studies on selectin blockers. 7. Structure-activity relationships of sialyl Lewis
      X mimetics based on modified Ser-Glu dipeptides.
AB  - We have previously found that heterochiral fucodipeptides, L-Ser-D-Glu (3a) and D
      Ser-L-Glu (3b), exhibited up to 20-100 times more potency than a sialyl Lewis X
      (sLeX, 1) and a 3'-sulfated Lewis X analogue (2) toward E-selectin binding and
      have also proposed, from molecular dynamics calculation, that their strong
      activities would depend on a possible formation of the type II and/or type II'
      beta-turn of compounds 3a,b (Tsukida, T.; Hiramatsu, Y.; Tsujishita, H.; Kiyoi,
      T.; Yoshida, M.; Kurokawa, K.; Moriyama, H.; Ohmoto, H.; Wada, Y.; Saito, T.;
      Kondo, H. J. Med. Chem. 1997, 40, 3534-3541). To clarify our hypothesis, we
      synthesized several analogues of compounds 3a,b and investigated their structure
      activity relationships. As a result, it was indicated that the type II and/or
      type II' beta-turn conformation would be a comparatively tight form and would
      play important roles in favorable binding to E-selectin. These findings indicate
      that sLeX mimetics with type II and type II' beta-turn dipeptides could be a
      useful methodology for the design of an active selectin blocker.

PMID- 9784104
TI  - Potent and selective non-cysteine-containing inhibitors of protein
      farnesyltransferase.
AB  - Potent and selective non-thiol-containing inhibitors of protein
      farnesyltransferase are described. FTI-276 (1) was transformed into pyridyl ether
      analogue 19. The potency of pyridyl ether 19 was improved by modification of the
      biphenyl core to that of an o-tolyl substituted biphenyl core to give 29. In
      addition to 0.4 nM in vitro potency, 29 displayed 350 nM potency in whole cells
      as the parent carboxylic acid. The o-tolyl biphenyl core dramatically and
      unexpectedly enhanced the potency of other compounds as exemplified by 46, 47,
      48, and 49.

PMID- 9784105
TI  - Synthesis of peptide aldehyde derivatives as selective inhibitors of human
      cathepsin L and their inhibitory effect on bone resorption.
AB  - Cathepsin L, a lysosomal cysteine protease, is secreted by osteoclasts and
      participates in bone collagen degradation. In a search for cathepsin L inhibitors
      as antiosteoporotic agents, a series of peptide aldehyde derivatives were
      prepared by two synthetic approaches, DMSO oxidation of the corresponding alcohol
      derivatives and DIBAL-H reduction of the corresponding N, O-dimethylhydroxylamide
      derivatives, and evaluated for inhibitory activity against human cathepsin L and
      for inhibitory effects on bone resorption. Some of the peptide aldehyde
      derivatives including alpha-acylamino aldehyde derivatives showed potent
      activities. Among these compounds, N-(1-naphthalenylsulfonyl-L-isoleucyl-L
      tryptophanal (12) was selected as a candidate for further investigation. Compound
      12, a potent, selective, and reversible inhibitor of human cathepsin L with an
      IC50 of 1.9 nM, inhibited the release of Ca2+ and hydroxyproline from bone in in
      vitro bone culture system and also prevented bone loss in ovariectomized mice at
      an oral dose of 50 mg/kg.

PMID- 9784107
TI  - Bis-cationic heteroaromatics as macrofilaricides: synthesis of bis-amidine and
      bis-guanylhydrazone derivatives of substituted imidazo[1,2-a]pyridines.
AB  - A series of guanylhydrazone, amidine, and hydrazone derivatives of 2
      phenylimidazo[1,2-a]pyridine have been prepared and evaluated for macrofilarial
      activity against Acanthocheilonema viteae and Brugia pahangi in jirds. Compounds
      with 4',6-bis-substitution by cyclic guanylhydrazone groups show activity. 4',6
      Bis-amidines show some activity but are more toxic; 4'- or 6-monosubstituted
      compounds are inactive. 2,6-Bis-substituted compounds lacking the phenyl ring are
      inactive. 4',6-Bis-substituted compounds having additional double bonds inserted
      between the heterocyclic ring and the phenyl ring or between the substituent and
      the ring system show reduced activity.

PMID- 9784106
TI  - Novel calcium antagonists with both calcium overload inhibition and antioxidant
      activity. 1. 2-(3, 5-di-tert-butyl-4-hydroxyphenyl)-3
      (aminopropyl)thiazolidinones.
AB  - A series of 2-(3, 5-di-tert-butyl-4-hydroxyphenyl)-3-(aminopropyl)thiazolidinones
      was synthesized in order to explore novel calcium antagonists with potent
      antiischemic activity. These compounds were designed to have, in addition to Ca2+
      antagonistic activity, both Ca2+ overload prevention and antioxidant activity in
      one molecule. These three kinds of activity were evaluated by using a K+
      depolarized rat aorta, a veratridine-induced Ca2+ overload model of rat
      cardiomyocytes, and a soybean lipoxygenase-induced lipid peroxidation model of
      rabbit low-density lipoprotein, respectively. In particular, 2-(3, 5-di-tert
      butyl-4-hydroxyphenyl)-3-[3-[N-methyl-N-[2-[3, 4
      (methylenedioxy)phenoxy]ethyl]amino]propyl]-1,3-thiazolidin-4-on e (7o) was found
      to be highly potent and possessed a well-balanced combination of these actions in
      vitro.

PMID- 9784108
TI  - Design of peptidomimetics that inhibit the association of phosphatidylinositol 3
      kinase with platelet-derived growth factor-beta receptor and possess cellular
      activity.
AB  - Phosphorylated tyrosine residues of growth factor receptors that associate with
      intracellular proteins containing src-homology 2 (SH2) domains are integral
      components in several signal transduction pathways related to proliferative
      diseases such as cancer, atherosclerosis, and restenosis. In particular, a
      phosphorylated pentapeptide [pTyr751-Val-Pro-Met754-Leu (pTyr = phosphotyrosine)]
      derived from the primary sequence of platelet-derived growth factor-beta (PDGF
      beta) receptor blocks the association of the C-terminal SH2 domain of the p85
      subunit of phosphatidylinositol 3-kinase (PI 3-kinase) to PDGF-beta receptor with
      an IC50 of 0.445 +/- 0.047 microM. Further evaluation of the structure-activity
      relationships for pTyr751-Val-Pro-Met-Leu resulted in the design of smaller
      peptidomimetics with enhanced affinity including Ac-pTyr-Val-Ala-N(C6H13)2 (IC50
      = 0.076 +/- 0.010 microM). In addition, the phosphotyrosine residue was replaced
      with a difluorophosphonate derivative [4-phosphono(difluoromethyl)phenylalanine
      (CF2Pmp)] which has been shown to be stable to cellular phosphatases. The
      extracellular administration of either CF2Pmp-Val-Pro-Met-Leu or Ac-CF2Pmp-Val
      Pro-Met-NH2 in a whole cell assay resulted in specific inhibition of the PDGF
      stimulated association from the C-terminal SH2 domain of the p85 subunit of PI 3
      kinase to the PDGF-beta receptor in a dose-dependent manner. These compounds were
      also effective in inhibiting GLUT4 translocation, c-fos expression, and cell
      membrane ruffling in single-cell microinjection assay.

PMID- 9784109
TI  - 5-Substituted pyrimidines with a 1,5-anhydro-2, 3-dideoxy-D-arabino-hexitol
      moiety at N-1: synthesis, antiviral activity, conformational analysis, and
      interaction with viral thymidine kinase.
AB  - A new series of anhydrohexitol nucleosides are described. These compounds have a
      pyrimidine base moiety substituted in the 5-position with a chloro (1b),
      trifluoromethyl (1c), vinyl (1d), 2-thienyl (1e), ethynyl (1f) or propynyl (1g)
      substituent. The vinyl, propynyl, and, in particular, the 5-trifluoromethyl
      analogue showed potent activity against herpes simplex virus (HSV), 1c with a
      selectivity index of >16000 against HSV-1 and >1000 against HSV-2. Conformational
      analysis of anhydrohexitol nucleosides using computational methods indicates that
      these nucleosides occur in an equilibrium between the C1 and 1C form with a
      DeltaE of 5.9 kJ/mol. When the anhydrohexitol nucleoside is cocrystallized with
      the HSV-1 thymidine kinase it adopts a 1C conformation, which is opposite to the
      conformation found for the small molecule alone. The enzyme, apparently, induces
      a conformational change, and conformational flexibility of an anhydrohexitol
      nucleoside may be advantageous for recognition by viral enzymes.

PMID- 9784110
TI  - 5-Benzylidene 1,2-dihydrochromeno[3,4-f]quinolines, a novel class of nonsteroidal
      human progesterone receptor agonists.
AB  - A novel series of nonsteroidal progestins, 5-benzylidene-1, 2-dihydrochromeno[3,4
      f]quinolines (2), was discovered, and a preliminary structure-activity
      relationship study around the 5-benzylidene ring generated several potent human
      progesterone receptor agonists (compounds 8, 16). These new progestins showed
      biological activities (EC50 = 5.7 and 7.6 nM) similar to progesterone (EC50 = 2.9
      nM) in the cotransfection assay with high efficacy (132% and 166%) and binding
      affinity (Ki = 0.66 and 0.83 nM) similar to medroxyprogesterone acetate (MPA) (Ki
      = 0.34 nM). A representative analogue, 8, demonstrated similar oral potency to
      MPA in the uterine wet weight/mammary gland morphology assay in ovariectomized
      rats.

PMID- 9784111
TI  - Bisquinolines. 2. Antimalarial N,N-bis(7-chloroquinolin-4
      yl)heteroalkanediamines.
AB  - N,N-Bis(7-chloroquinolin-4-yl)heteroalkanediamines 1-11 were synthesized and
      screened against Plasmodium falciparum in vitro and Plasmodium berghei in vivo.
      These bisquinolines had IC50 values from 1 to 100 nM against P. falciparum in
      vitro. Six of the 11 bisquinolines were significantly more potent against the
      chloroquine-resistant W2 clone compared to the chloroquine-sensitive D6 clone.
      For bisquinolines 1-11 there was no relationship between the length of the
      bisquinoline heteroalkane bridge and antimalarial activity and no correlation
      between in vitro and in vivo antimalarial activities. Bisquinolines with alkyl
      ether and piperazine bridges were substantially more effective than bisquinolines
      with alkylamine bridges against P. berghei in vivo. Bisquinolines 1-10 were
      potent inhibitors of hematin polymerization with IC50 values falling in the
      narrow range of 5-20 microM, and there was a correlation between potency of
      inhibition of hematin polymerization and inhibition of parasite growth. Compared
      to alkane-bridged bisquinolines (Vennerstrom et al., 1992), none of these
      heteroalkane-bridged bisquinolines had sufficient antimalarial activity to
      warrant further investigation of the series.

PMID- 9784112
TI  - Synthesis and tyrosine kinase inhibitory activity of a series of 2-amino-8H
      pyrido[2,3-d]pyrimidines: identification of potent, selective platelet-derived
      growth factor receptor tyrosine kinase inhibitors.
AB  - Screening of a compound library led to the identification of 2-amino-6-(2,6
      dichlorophenyl)-8-methylpyrido[2,3-d]pyrimidine (1) as a inhibitor of the
      platelet-derived growth factor receptor (PDGFr), fibroblast growth factor
      receptor (FGFr), and c-src tyrosine kinases (TKs). Replacement of the primary
      amino group at C-2 of 1 with a 4-(N,N-diethylaminoethoxy)phenylamino group
      yielded 2a, which had greatly increased activity against all three TKs. In the
      present work, variation of the aromatic group at C-6 and of the alkyl group at N
      8 of the pyrido[2,3-d]pyrimidine core provided several analogues that retained
      potency, including derivatives that were biased toward inhibition of the TK
      activity of PDGFr. Analogues of 2a with a 3-thiophene or an unsubstituted phenyl
      group at C-6 were the most potent inhibitors. Compound 54, which had IC50 values
      of 31, 88, and 31 nM against PDGFr, FGFr, and c-src TK activity, respectively,
      was active in a variety of PDGF-dependent cellular assays and blocked the in vivo
      growth of three PDGF-dependent tumor lines.

PMID- 9784113
TI  - Muscarinic agonists with antipsychotic-like activity: structure-activity
      relationships of 1,2,5-thiadiazole analogues with functional dopamine antagonist
      activity.
AB  - Muscarinic agonists were tested in two models indicative of clinical
      antipsychotic activity: conditioned avoidance responding (CAR) in rats and
      inhibition of apomorphine-induced climbing in mice. The standard muscarinic
      agonists oxotremorine and pilocarpine were both active in these tests but showed
      little separation between efficacy and cholinergic side effects. Structure
      activity relationships of the alkylthio-1,2,5-thiadiazole azacyclic type
      muscarinic partial agonists are shown, revealing the exo-6-(3-propyl/butylthio
      1,2, 5-thiadiazol-4-yl)-1-azabicyclo[3.2.1]octane analogues (4a,b and 9a, b) to
      be the most potent antipsychotic agents with large separation between efficacy
      and cholinergic side effects. The lack of enantiomeric selectivity suggests the
      pharmacophoric elements are in the mirror plane of the compounds. A model
      explaining the potency differences of closely related compounds is offered. The
      data suggest that muscarinic agonists act as functional dopamine antagonists and
      that they could become a novel treatment of psychotic patients.

PMID- 9784114
TI  - CoMFA-based prediction of agonist affinities at recombinant D1 vs D2 dopamine
      receptors.
AB  - We have previously shown that using agonist affinity at recombinant receptors
      selectively expressed in clonal cells as the dependent variable in three
      dimensional quantitative structure-activity relationship studies (3D-QSAR)
      presents a unique opportunity for accuracy and precision in measurement. Thus, a
      comparison of affinity's structural determinants for a set of compounds at two
      different recombinant dopamine receptors represents an attainable goal for 3D
      QSAR. A molecular database of bound conformations of 16 structurally diverse
      agonists was established by alignment with a high-affinity template compound for
      the D1 receptor, 3-allyl-6-bromo-7,8-dihydroxy-1-phenyl-2,3,4, 5-tetrahydro-1H
      benzazepin. A second molecular database of the bound conformations of the same
      compounds was established against a second template for the D2 receptor,
      bromocriptine. These aligned structures suggested three-point pharmacophore maps
      (one cationic nitrogen and two electronegative centers) for the two dopamine
      receptors, which differed primarily in the height of the nitrogen above the plane
      of the catechol ring and in the nature of the hydrogen-bonding region. The
      ln(1/KL) values for the low-affinity agonist binding conformation at recombinant
      D1 and D2 dopamine receptors stably expressed in C6 glioma cells were used as the
      target property for the CoMFA (comparative molecular field analysis) of the 16
      aligned structures. The resulting CoMFA models yielded cross-validated R2 (q2)
      values (standard error of prediction) of 0. 879 (1.471, with five principal
      components) and 0.834 (1.652, with five principal components) for D1 and D2
      affinity, respectively. The simple R2 values (standard error of the estimate)
      were 0.994 (0.323) and 0.999 (0.116), respectively, for D1 and D2 receptor. F
      values were 341 and 2465 for D1 and D2 models, respectively, with 5 and 10 df.
      The predictive utility of the CoMFA model was evaluated at both receptors using
      the dopamine agonists, apomorphine and 7-OH-DPAT. Predictions of KL were accurate
      at both receptors. Flexible 3D searches of several chemical databases (NCI, MDDR,
      CMC, ACD, and Maybridge) were done using basic pharmacophore models at each
      receptor to determine the similarity of hit lists between the two models. The D1
      and D2 models yielded different lists of lead compounds. Several of the lead
      compounds closely resembled high-affinity training set compounds. Finally,
      homology modeling of agonist binding to the D2 receptor revealed some
      consistencies and inconsistencies with the CoMFA-derived D2 model and provided a
      possible rationale for features of the D2 CoMFA contour map. Together these
      results suggest that CoMFA-homology based models may provide useful insights
      concerning differential agonist-receptor interactions at related receptors. The
      results also suggest that comparisons of CoMFA models for two structurally
      related receptors may be a fruitful approach for differential QSAR.

PMID- 9784115
TI  - Potent cyano and carboxamido side-chain analogues of 1', 1'-dimethyl-delta8
      tetrahydrocannabinol.
AB  - The synthesis and pharmacological profile of several cyano (1a-e) and carboxamido
      (2a-h) side-chain-substituted analogues of 1', 1'-dimethyl-Delta8-THC are
      described. Commercially available cyano compound 3 was transformed to the
      resorcinol 6 in a three-step sequence. Condensation of 6 with p-menth-2-ene-1,8
      diol formed the THC 7a which, with sodium cyanide/DMSO, gave 1b. Protection of
      the phenol in 7a as the MOM derivative provided the common intermediate 8 for the
      synthesis of 1a,c,e. Compound 1d was also synthesized from 7a via the aldehyde
      9a. Base hydrolysis of 1b gave the acid 10 which, via its acid chloride and
      subsequent treatment with the appropriate amine, formed the target compounds 2a
      h. The pharmacological profile indicated that the cyano analogues 1a-e had very
      high CB1 binding affinity (0.36-13 nM) and high in vivo potency as agonists. Two
      analogues (1a,b) had extremely high potency in the mouse tetrad tests. The
      dimethylcarboxamido analogue 2a showed a similar profile to 1a,b. The high
      potency was also retained in analogue 2c. In contrast the sulfonamide analogue 2d
      was unique as it had greater affinity than Delta9-THC, yet it was practically
      devoid of agonist effects. This study suggests that the incorporation of a cyano
      or an amide substituent in the side chain of Delta8-THC-DMH can enhance potency
      and can also lead to compounds with a unique profile which have high binding
      affinity and are practically devoid of agonist effects.

PMID- 9784116
TI  - Inhibitors of acyl-CoA:cholesterol O-acyltransferase. 3. Discovery of a novel
      series of N-alkyl-N-[(fluorophenoxy)benzyl]-N'-arylureas with weak toxicological
      effects on adrenal glands.
AB  - A series of N-alkyl-N-[(fluorophenoxy)benzyl]-N'-arylureas were prepared and
      evaluated for their ability to inhibit intestinal acyl-CoA:cholesterol O
      acyltransferase and to inhibit accumulation of cholesteryl esters in macrophages
      in vitro. In vivo hypocholesterolemic activity was assessed in cholesterol-fed
      rats by oral administration as a dietary admixture and/or by gavage in a PEG400
      vehicle. Modification of the alkyl substituent on the N'-aryl moiety and on the
      urea nitrogen significantly influenced macrophage assay in vitro. Toxicological
      study revealed a distinct relationship between macrophage assay and the toxicity
      observed in adrenal glands of rabbits treated with representatives of this series
      of compounds. Investigations utilizing the macrophage assay as an indicator for
      adrenal toxicity led to the identification of compounds 1g (FR190809) and 1k
      (FR186485, or FR195249 as its hydrochloride salt) as potent, nonadrenotoxic,
      orally efficacious ACAT inhibitors irrespective of the administration method.

PMID- 9784118
TI  - Plant comparative genetics after 10 years.
AB  - The past 10 years have seen the discovery of unexpected levels of conservation of
      gene content and gene orders over millions of years of evolution within grasses,
      crucifers, legumes, some trees, and Solanaceae crops. Within the grasses, which
      include the three 500-million-ton-plus-per-year crops (wheat, maize, and rice),
      and the crucifers, which include all the Brassica crops, colinearity looks good
      enough to do most map-based cloning only in the small genome model species, rice
      and Arabidopsis. Elsewhere, knowledge gained in a few major crops is being pooled
      and applied across the board. The extrapolation of information from the well
      studied species to orphan crops, which include many tropical species, is
      providing a solid base for their improvement. Genome rearrangements are giving
      new insights into evolution. In fact, comparative genetics is the key that will
      unlock the secrets of crop plants with genomes larger than that of humans.

PMID- 9784117
TI  - Bisphenols that stimulate cells to release alkali metal cations: a structure
      activity study.
AB  - The laxative action of phenolphthalein (5) is believed to result from induction
      of potassium and water efflux from the colon epithelium. In cultured cells, K+
      efflux is promoted by 5 and by a contaminant (1) present in commercial phenol
      red. Six compounds with chemical structures related to those of 5 and 1 were
      tested for ability to induce the release of 86Rb from COS-7 cells preloaded with
      this isotope: 4,4'-(9-fluorenylidene)diphenol (2), 4, 4'-(9
      fluorenylidene)dianiline, 4, 4'-(9-fluorenylidene)bisphenoxyethanol, 1,1'-bi-2
      naphthol, 4, 4'-biphenol, and bis(4-hydroxyphenyl)methane. With one exception
      these compounds were all inactive at a concentration of 10 microM. However, 2
      caused profound 86Rb efflux at concentrations as low as 100 nM. Concentrations of
      5 1-2 orders of magnitude higher were needed to achieve similar levels of
      activity. The three compounds known to be active in this experimental system
      share a common feature that is absent in all the inactive compounds: a five
      membered ring structure, one of whose carbon atoms is disubstituted with p
      hydroxyphenyl residues. Because 2 and 5 are readily available, comparative
      studies on the mechanism of action of these biphenols at the cellular level can
      now be undertaken.

PMID- 9784119
TI  - Databases in genomic research.
AB  - Genome-related databases have already become an invaluable part of the scientific
      landscape. The role played by these databases will only increase as the volume
      and complexity of relevant biology data rapidly expand. We are far enough into
      the genome project and into the development of these databases to assess their
      attributes and to reexamine some of the conceptual organizations and approaches
      they are taking. It is clear that there are needs for both highly detailed and
      simplified database views, the latter being especially needed to make expert
      domain data more accessible to nonspecialists.

PMID- 9784120
TI  - Arabidopsis thaliana: a model plant for genome analysis.
AB  - Arabidopsis thaliana is a small plant in the mustard family that has become the
      model system of choice for research in plant biology. Significant advances in
      understanding plant growth and development have been made by focusing on the
      molecular genetics of this simple angiosperm. The 120-megabase genome of
      Arabidopsis is organized into five chromosomes and contains an estimated 20,000
      genes. More than 30 megabases of annotated genomic sequence has already been
      deposited in GenBank by a consortium of laboratories in Europe, Japan, and the
      United States. The entire genome is scheduled to be sequenced by the end of the
      year 2000. Reaching this milestone should enhance the value of Arabidopsis as a
      model for plant biology and the analysis of complex organisms in general.

PMID- 9784121
TI  - New goals for the U.S. Human Genome Project: 1998-2003.
AB  - The Human Genome Project has successfully completed all the major goals in its
      current 5-year plan, covering the period 1993-98. A new plan, for 1998-2003, is
      presented, in which human DNA sequencing will be the major emphasis. An ambitious
      schedule has been set to complete the full sequence by the end of 2003, 2 years
      ahead of previous projections. In the course of completing the sequence, a
      "working draft" of the human sequence will be produced by the end of 2001. The
      plan also includes goals for sequencing technology development; for studying
      human genome sequence variation; for developing technology for functional
      genomics; for completing the sequence of Caenorhabditis elegans and Drosophila
      melanogaster and starting the mouse genome; for studying the ethical, legal, and
      social implications of genome research; for bioinformatics and computational
      studies; and for training of genome scientists.

PMID- 9784123
TI  - Unconditional quantum teleportation 
AB  - Quantum teleportation of optical coherent states was demonstrated experimentally
      using squeezed-state entanglement. The quantum nature of the achieved
      teleportation was verified by the experimentally determined fidelity Fexp = 0.58
      +/- 0.02, which describes the match between input and output states. A fidelity
      greater than 0.5 is not possible for coherent states without the use of
      entanglement. This is the first realization of unconditional quantum
      teleportation where every state entering the device is actually teleported.

PMID- 9784124
TI  - Three-dimensional structure at the base of the mantle beneath the central pacific
AB  - Forward modeling of differential travel times of phases sensitive to lowermost
      mantle beneath the central Pacific reveals lateral heterogeneity that is higher
      in amplitude than predicted by tomographic models. A broad zone of low S velocity
      (-4 percent with respect to standard models), which may correspond to the base of
      a thermal "plume," narrows and is deflected as it extends to about 1000
      kilometers above the core-mantle boundary. To the east of this zone, a localized
      region of fast S velocity (+5 percent) suggests strong heterogeneity or
      anisotropy related to the presence of high pressure and temperature assemblages,
      which may or may not involve core material. Its presence could also explain the
      observation of precursors to core reflected phases in this region.

PMID- 9784122
TI  - The transcriptional program of sporulation in budding yeast.
AB  - Diploid cells of budding yeast produce haploid cells through the developmental
      program of sporulation, which consists of meiosis and spore morphogenesis. DNA
      microarrays containing nearly every yeast gene were used to assay changes in gene
      expression during sporulation. At least seven distinct temporal patterns of
      induction were observed. The transcription factor Ndt80 appeared to be important
      for induction of a large group of genes at the end of meiotic prophase. Consensus
      sequences known or proposed to be responsible for temporal regulation could be
      identified solely from analysis of sequences of coordinately expressed genes. The
      temporal expression pattern provided clues to potential functions of hundreds of
      previously uncharacterized genes, some of which have vertebrate homologs that may
      function during gametogenesis.

PMID- 9784126
TI  - Thermodynamics of calcite growth: baseline for understanding biomineral formation
AB  - The complexity of biomineralized structures suggests the potential of organic
      constituents for controlling energetic factors during crystal synthesis. Atomic
      force microscopy was used to investigate the thermodynamic controls on carbonate
      growth and to measure the dependence of step speed on step length and the
      dependence of critical step length on supersaturation in precisely controlled
      solutions. These data were used to test the classic Gibbs-Thomson relationship
      and provided the step edge free energies and free energy barriers to one
      dimension nucleation for calcite. Addition of aspartic acid, a common component
      in biomineralizing systems, dramatically affected growth morphology and altered
      the magnitude of the surface energy.

PMID- 9784125
TI  - Pressure-induced landau-type transition in stishovite 
AB  - A Rietveld structural analysis of stishovite, with angle-dispersive x-ray
      diffraction synchrotron source at the European Synchrotron Radiation Facility,
      confirmed a CaCl2 form of stishovite distortion at 54 +/- 1 gigapascals but
      confirmed no further phase transformation up to 120 gigapascals. The deviatoric
      stress that is usually encountered at such pressures was relaxed after yttrium
      aluminum-garnet-laser heating. A single Birch-Murnaghan equation of state fits
      volumes of stishovite and a CaCl2 form, showing that the tetragonal distortion
      occurs without a substantial change in volume. At the 54-gigapascal transition,
      the pressure-induced lattice modifications were similar to those found in a
      Landau-type temperature-induced transition. It is proposed that, above the
      transition pressure, the critical temperature increases above 300 kelvin, so that
      the lower entropy form becomes stable.

PMID- 9784127
TI  - Predictability in the midst of chaos: A scientific basis for climate forecasting 
AB  - The Earth's atmosphere is generally considered to be an example of a chaotic
      system that is sensitively dependent on initial conditions. It is shown here that
      certain regions of the atmosphere are an exception. Wind patterns and rainfall in
      certain regions of the tropics are so strongly determined by the temperature of
      the underlying sea surface that they do not show sensitive dependence on the
      initial conditions of the atmosphere. Therefore, it should be possible to predict
      the large-scale tropical circulation and rainfall for as long as the ocean
      temperature can be predicted. If changes in tropical Pacific sea-surface
      temperature are quite large, even the extratropical circulation over some
      regions, especially over the Pacific-North American sector, is predictable.

PMID- 9784128
TI  - Climate and groundwater recharge during the last glaciation in an ice-covered
      region 
AB  - A multitracer study of a small aquifer in northern Switzerland indicates that the
      atmosphere in central Europe cooled by at least 5 degreesC during the last
      glacial period. The relation between oxygen isotope ratios (delta18O) and
      recharge temperatures reconstructed for this period is similar to the present-day
      one if a shift in the delta18O value of the oceans during the ice age is taken
      into account. This similarity suggests that the present-day delta18O-temperature
      relation can be used to reconstruct paleoclimate conditions in northern
      Switzerland. A gap in calculated groundwater age between about 17,000 and 25,000
      years before the present indicates that during the last glacial maximum, local
      groundwater recharge was prevented by overlying glaciers.

PMID- 9784129
TI  - Self-organized growth of three- dimensional quantum-Dot crystals with fcc-like
      stacking and a tunable lattice constant 
AB  - The self-organization of pyramidal PbSe islands that spontaneously form during
      strained-layer epitaxial growth of PbSe/Pb1-xEuxTe (x = 0.05 to 0.1)
      superlattices results in the formation of three-dimensional quantum-dot crystals.
      In these crystals, the dots are arranged in a trigonal lattice with a face
      centered cubic (fcc)-like A-B-C-A-B-C vertical stacking sequence. The lattice
      constant of the dot crystal can be tuned continuously by changing the
      superlattice period. As shown by theoretical calculations, the elastic anisotropy
      in these artificial dot crystals acts in a manner similar to that of the directed
      chemical bonds of crystalline solids. The narrow size distribution and excellent
      control of the dot arrangement may be advantageous for optoelectronic device
      applications.

PMID- 9784130
TI  - Rapid identification of subtype-selective agonists of the somatostatin receptor
      through combinatorial chemistry.
AB  - Nonpeptide agonists of each of the five somatostatin receptors were identified in
      combinatorial libraries constructed on the basis of molecular modeling of known
      peptide agonists. In vitro experiments using these selective compounds
      demonstrated the role of the somatostatin subtype-2 receptor in inhibition of
      glucagon release from mouse pancreatic alpha cells and the somatostatin subtype-5
      receptor as a mediator of insulin secretion from pancreatic beta cells. Both
      receptors regulated growth hormone release from the rat anterior pituitary gland.
      The availability of high-affinity, subtype-selective agonists for each of the
      somatostatin receptors provides a direct approach to defining their physiological
      functions.

PMID- 9784131
TI  - Pathways to a protein folding intermediate observed in a 1-microsecond simulation
      in aqueous solution.
AB  - An implementation of classical molecular dynamics on parallel computers of
      increased efficiency has enabled a simulation of protein folding with explicit
      representation of water for 1 microsecond, about two orders of magnitude longer
      than the longest simulation of a protein in water reported to date. Starting with
      an unfolded state of villin headpiece subdomain, hydrophobic collapse and helix
      formation occur in an initial phase, followed by conformational readjustments. A
      marginally stable state, which has a lifetime of about 150 nanoseconds, a
      favorable solvation free energy, and shows significant resemblance to the native
      structure, is observed; two pathways to this state have been found.

PMID- 9784133
TI  - Ordering of the numerosities 1 to 9 by monkeys.
AB  - A fundamental question in cognitive science is whether animals can represent
      numerosity (a property of a stimulus that is defined by the number of
      discriminable elements it contains) and use numerical representations
      computationally. Here, it was shown that rhesus monkeys represent the numerosity
      of visual stimuli and detect their ordinal disparity. Two monkeys were first
      trained to respond to exemplars of the numerosities 1 to 4 in an ascending
      numerical order (1 --> 2 --> 3 --> 4). As a control for non-numerical cues,
      exemplars were varied with respect to size, shape, and color. The monkeys were
      later tested, without reward, on their ability to order stimulus pairs composed
      of the novel numerosities 5 to 9. Both monkeys responded in an ascending order to
      the novel numerosities. These results show that rhesus monkeys represent the
      numerosities 1 to 9 on an ordinal scale.

PMID- 9784134
TI  - Smart engineering in the mid-carboniferous: how well could palaeozoic dragonflies
      Fly? 
AB  - The wings of archaic Odonatoidea from the mid-Carboniferous of Argentina show
      features analogous to "smart" mechanisms in modern dragonflies that are
      associated with the agile, versatile flight necessary to catch prey in flight.
      These mechanisms act automatically in flight to depress the trailing edge and to
      facilitate wing twisting, in response to aerodynamic loading. The presence of
      similar features suggests that the earliest known odonatoids were already
      becoming adapted for high-performance flight in association with a predatory
      habit.

PMID- 9784132
TI  - A physical map of 30,000 human genes.
AB  - A map of 30,181 human gene-based markers was assembled and integrated with the
      current genetic map by radiation hybrid mapping. The new gene map contains nearly
      twice as many genes as the previous release, includes most genes that encode
      proteins of known function, and is twofold to threefold more accurate than the
      previous version. A redesigned, more informative and functional World Wide Web
      site (www.ncbi.nlm.nih.gov/genemap) provides the mapping information and
      associated data and annotations. This resource constitutes an important
      infrastructure and tool for the study of complex genetic traits, the positional
      cloning of disease genes, the cross-referencing of mammalian genomes, and
      validated human transcribed sequences for large-scale studies of gene expression.

PMID- 9784135
TI  - An MTP inhibitor that normalizes atherogenic lipoprotein levels in WHHL rabbits.
AB  - Patients with abetalipoproteinemia, a disease caused by defects in the microsomal
      triglyceride transfer protein (MTP), do not produce apolipoprotein B-containing
      lipoproteins. It was hypothesized that small molecule inhibitors of MTP would
      prevent the assembly and secretion of these atherogenic lipoproteins. To test
      this hypothesis, two compounds identified in a high-throughput screen for MTP
      inhibitors were used to direct the synthesis of a highly potent MTP inhibitor.
      This molecule (compound 9) inhibited the production of lipoprotein particles in
      rodent models and normalized plasma lipoprotein levels in Watanabe-heritable
      hyperlipidemic (WHHL) rabbits, which are a model for human homozygous familial
      hypercholesterolemia. These results suggest that compound 9, or derivatives
      thereof, has potential applications for the therapeutic lowering of atherogenic
      lipoprotein levels in humans.

PMID- 9784136
TI  - Genome sequence of an obligate intracellular pathogen of humans: Chlamydia
      trachomatis.
AB  - Analysis of the 1,042,519-base pair Chlamydia trachomatis genome revealed
      unexpected features related to the complex biology of chlamydiae. Although
      chlamydiae lack many biosynthetic capabilities, they retain functions for
      performing key steps and interconversions of metabolites obtained from their
      mammalian host cells. Numerous potential virulence-associated proteins also were
      characterized. Several eukaryotic chromatin-associated domain proteins were
      identified, suggesting a eukaryotic-like mechanism for chlamydial nucleoid
      condensation and decondensation. The phylogenetic mosaic of chlamydial genes,
      including a large number of genes with phylogenetic origins from eukaryotes,
      implies a complex evolution for adaptation to obligate intracellular parasitism.

PMID- 9784138
TI  - ONg retroviral particles in chick cell grown vaccines.

PMID- 9784137
TI  - Attenuation of virulence by disruption of the Mycobacterium tuberculosis erp
      gene.
AB  - The virulence of the mycobacteria that cause tuberculosis depends on their
      ability to multiply in mammalian hosts. Disruption of the bacterial erp gene,
      which encodes the exported repetitive protein, impaired multiplication of M.
      tuberculosis and M. bovis Bacille Calmette-Guerin in cultured macrophages and
      mice. Reintroduction of erp into the mutants restored their ability to multiply.
      These results indicate that erp contributes to the virulence of M. tuberculosis.

PMID- 9784139
TI  - The reverse transcriptase activity in cell-free medium of chicken embryo
      fibroblast cultures is not associated with a replication-competent retrovirus.
AB  - BACKGROUND: Reverse transcriptase (RT) activity has previously been reported in
      concentrated medium of primary chicken embryo cell cultures using the traditional
      RT assay. Recently, using the newly-developed and highly-sensitive product
      enhanced reverse transcriptase (PERT) assay, RT activity has been detected in
      live, attenuated vaccines grown in chicken cell substrates. Furthermore, this
      activity has been associated with particles that contain RNA related to an
      ancient, endogenous avian retrovirus family designated as EAV-0. OBJECTIVE: To
      investigate whether the RT activity present in vaccines produced in specific
      pathogen-free chicken cell substrates is associated with an infectious retrovirus
      that can replicate in human cells. STUDY DESIGN: The kinetics of RT activity
      produced by 10-day-old chicken embryo fibroblast (CEF) cultures was determined by
      analyzing cell-free medium in a PCR-based RT (PBRT) assay. Material containing
      the peak PBRT activity was used as the inoculum to infect various human cell
      lines and peripheral blood mononuclear cells. Filtered supernatants from control
      and test cultures were analyzed for the presence of replication-competent
      retroviruses by the PBRT assay. The cells were monitored for other adventitious
      agents by routine observation for cytopathic effect (CPE) and by transmission
      electron microscopy (TEM) at culture termination. RESULTS: The PBRT activity did
      not increase above the background level in the human target cells through at
      least five cell passages, thus indicating the absence of a replicating
      retrovirus. No other adventitious agents were detected based upon TEM analysis
      and the absence of CPE. CONCLUSION: The RT activity produced by chicken primary
      cell cultures is not associated with a retrovirus that can replicate in human
      cells.

PMID- 9784140
TI  - Analysis of a coded panel of licensed vaccines by polymerase chain reaction-based
      reverse transcriptase assays: a collaborative study [seecomments].
AB  - BACKGROUND: A recent publication reporting the presence of low levels of reverse
      transcriptase (RT) activity in certain vaccines for human use necessitated that
      regulatory agencies address the issue of whether this RT activity presented a
      risk to humans. Detection of low levels of RT activity corresponding to fewer
      than ten virions became possible with the development of highly-sensitive
      polymerase chain reaction (PCR)-based RT (PBRT) assays. Variations of the PBRT
      assay were developed in three laboratories. These assays were reported as being
      at least one million-fold more sensitive than conventional RT assays. OBJECTIVE:
      To ascertain the sensitivity and reliability of PBRT assays in different
      laboratories and to determine which vaccine samples possessed RT activity. STUDY
      DESIGN: Coded panels of licensed vaccines together with positive and negative
      controls was assembled at the Center for Biologics Evaluation and Research (CBER)
      of the Food and Drug Administration (FDA) and distributed to five cooperating
      laboratories as well as to our laboratory at CBER. Each laboratory carried out
      their version of the PBRT assay and submitted the results to the coordinator at
      CBER. RESULTS: Results of the PBRT analyses carried out in the six laboratories
      are presented. Five of the six laboratories reported results that were highly
      consistent. RT activity was detected in live attenuated vaccines that were
      prepared in chick embryo cells (mumps, measles and yellow fever), but very low or
      undetectable RT activity was found in vaccines produced in mammalian cells
      (rabies and rubella). Influenza vaccines from several manufacturers included in
      the panel displayed the most variability, with different products of this
      inactivated vaccine having differing amounts of RT activity. CONCLUSIONS: Only
      vaccines produced in chick embryo cells had significant RT activity. Because RT
      activity was present in the allantoic fluid of uninfected chick embryos and
      culture medium from chick embryo fibroblasts, the RT activity arises from the
      cell substrate used for vaccine production. The PBRT assays were reliably able to
      detect the low levels of RT activity in chicken-derived vaccines.

PMID- 9784141
TI  - A simplified assay for screening of drug resistance of cell-associated
      cytomegalovirus strains.
AB  - BACKGROUND: Conventional phenotypic drug resistance determination of cell-free
      clinical human cytomegalovirus (HCMV) isolates is usually very laborious and may
      take 8-12 weeks, since serially passages of slowly growing viral isolates in
      tissue cultures are required to obtain a sufficient viral titer for an
      appropriate inoculum. Rapid screening of a large number of samples would
      therefore only be possible if simplified, less work-intensive methods are
      employed. OBJECTIVE: The aim of this work was to develop an assay which speeds up
      the whole procedure of phenotypic drug resistance determination. Steps of the
      classical plaque reduction assay should be simplified or omitted, but on the
      other hand, the assay should be reliable and reproducible. STUDY DESIGN: Twenty
      six clinical HCMV isolates from 20 immunocompromised patients (ten pre-treatment
      and 16 post-treatment with ganciclovir) were tested for drug susceptibility with
      the simplified plaque reduction assay. Most isolates were tested at least twice
      in independent assays. Virus titration could be avoided by using four different
      doses of cell-associated virus from the secondary culture for coculture
      susceptibility testing. Drug susceptibility values were determined by plaque
      titration and Probit analysis. RESULTS: All clinical HCMV isolates tested showed
      a mean ganciclovir ID50 value of 1.98 microM, (range 0.2-12.2; median 0.95) and a
      mean foscarnet ID50 value of 92.4 microM (range 35.7-181; median 81). All except
      one isolate were classified ganciclovir sensitive when compared to ID50 values of
      two ganciclovir resistant control stains (53.7 +/- 6.4 and 12.7 +/- 0.9 microM)
      and the sensitive laboratory strain Towne (2.1 +/- 0.8 microM). Repeated tests of
      individual isolates were reproducible, although the infectivity of the inoculum
      has not been determined prior of the assay. The mean time which elapsed between
      receipt of the clinical specimen and read-out of the assay was circa 4 weeks.
      CONCLUSIONS: Phenotypic resistance testing of HCMV isolates following to this
      protocol drastically reduces expenditure of time and work. The assay allows
      reliably the discrimination of HCMV isolates as drug resistant or sensitive
      according to the recent classification criteria of the AIDS Clinical Trials Group
      (ACTG). The simple handling and uncomplicated calibration of this assay
      facilitates the screening of large specimen numbers and renders drug
      susceptibility determination of HCMV more accessible to diagnostic routine use.

PMID- 9784142
TI  - Evaluation of epidemiological and serological predictors of human
      immunodeficiency virus type-1 (HIV-1) infection among high risk professional
      blood donors with western blot indeterminate results.
AB  - BACKGROUND: Indeterminate pattern of results in Western blot (WBI) for human
      immunodeficiency virus type-1 (HIV-1) infection may represent early HIV-1
      infection or may be non-specific in origin. This issue can be resolved by follow
      up testing upto at least 6 months resulting in psychological distress as well as
      in high drop out rates among those undergoing investigation pointing out the need
      for additional parameters that could help in determining the status of HIV-1
      infection at the time of initial testing itself in individuals with WBI pattern.
      OBJECTIVE: The objectives of the present study were: (i) to determine the
      frequency of HIV-1 infected individuals in a group of professional donors showing
      WBI patterns in initial testing on the basis of follow up serological studies;
      (ii) to find out if any HIV related epidemiological or serological
      characteristics recorded at the time of initial testing could be considered as
      predictor for HIV-1 infection in WBI specimens; and (iii) to evaluate two
      alternative serodiagnostic strategies for HIV-1 infection viz. multiple EIAs
      based on different antigen preparations/principles and a line immunoassay (LIA)
      employing recombinant antigens in resolving status of HIV-1 infection in
      specimens showing WBI results at initial testing. STUDY DESIGN: Professional
      donors with WBI patterns belonging to EIA reactive and EIA nonreactive groups
      were subjected to study of epidemiological profile, prevalence of sexually
      transmitted diseases (STD) markers and follow up serological testing for HIV-1 at
      6, 12, 24 and 48 weeks intervals to record any seroconversion. The initial and
      follow up specimens from the donors with initial WBI results were subjected to
      two EIAs (one based on dot immunoassay using synthetic HIV-1 antigens and other
      based on microwell EIA using recombinant HIV-1 proteins) as well as to LIA.
      RESULTS: Professional donors with initial WBI results, from the EIA reactive
      group had higher proportion of unmarried individuals (90.3%), with history of
      heterosexual promiscuity (75%) and visit to STD clinics (36.1%) compared with the
      WBI donors from the EIA nonreactive group (72.7, 42.4 and 12.1%, respectively, P
      values < 0.001). Prevalence of antitreponemal antibodies was higher in the former
      group (16.7%) compared with the later group (1.5%, P value < 0.002).
      Seroconversion was recorded in 4 (7.3%) out of 55 EIA reactive WBI donors from
      the EIA reactive group that were characterised by high optical density (OD)
      values in EIA, 'p24 only' pattern of band in WB and positivity by LIA at the time
      of initial testing. LIA was found to be more reliable test compared with
      combination of EIAs to determine status of HIV-1 infection in WBI specimens at
      the time of initial testing. CONCLUSION: The present study points out that
      parameters like history of heterosexual promiscuity, prevalence of STD markers,
      high OD values in screening EIA, 'p24' only pattern of bands in WB and positivity
      by LIA could have individual predictive values for HIV-1 infection in specimens
      showing WBI pattern of results at initial testing.

PMID- 9784143
TI  - Use of the human cytomegalovirus (HCMV) antigenemia assay for diagnosis and
      monitoring of HCMV infections and detection of antiviral drug resistance in the
      immunocompromised.
AB  - BACKGROUND: Quantification of viral load in blood has proven to be helpful in the
      follow-up of disseminated HCMV infections in immunocompromised patients.
      OBJECTIVES: (i) To describe the antigenemia assay and its optimization and (ii)
      to analyze the use of the antigenemia assay for the diagnosis and monitoring of
      HCMV infections and for the detection of treatment failures. STUDY DESIGN: This
      article is intended to give an overview of our experience in the use of the
      antigenemia assay. RESULTS AND CONCLUSIONS: In solid organ transplant recipients
      and patients with AIDS, HCMV symptomatic infections mostly appear when
      antigenemia values are > 300 pp65-positive PBL/2 x 10(5) examined. To avoid the
      appearance of overt HCMV disease antiviral treatment could be administered when
      antigenemia levels are > 100 pp65-positive PBL/2 x 10(5) examined. Bone marrow
      transplant recipients show symptomatic HCMV infections when antigenemia values
      are > 100 pp65-positive PBL/2 x 10(5) examined. This group of patients should be
      treated when antigenemia levels are < 10 pp65-positive PBL/2 x 10(5) examined due
      to the higher mortality rate associated with HCMV complications. A decrease in
      antigenemia levels during therapy indicates a good response to antiviral drug,
      while stable or increasing values document a treatment failure and the emergence
      of drug-resistant HCMV strains.

PMID- 9784144
TI  - Comparison of rhabdomyosarcoma, buffalo green monkey kidney epithelial, A549
      (human lung epithelial) cells and human embryonic lung fibroblasts for isolation
      of enteroviruses from clinical samples.
AB  - BACKGROUND: Traditionally, primary monkey kidney (PMK) epithelial cells have been
      one of the more widely used cell types for the isolation of enteroviruses from
      clinical samples. For the isolation of coxsackie A viruses, intraperitoneal
      inoculation of newborn mice has been used in some laboratories. OBJECTIVE: With
      the discontinued availability of PMK epithelial cells and the reported growth of
      coxsackie A viruses in rhabdomyosarcoma cells (RD), we compared the use of the
      latter cell line with our routinely used microwell cell cultures. STUDY DESIGN:
      Microwell cell cultures of buffalo green monkey epithelial cell line (BGM), human
      lung carcinoma epithelial cell line (A549) and human embryonic lung (HEL)
      fibroblasts were compared with RD cell line for the isolation of enteroviruses
      from clinical samples. RESULTS: A total of 39 enteroviruses was isolated from
      3517 specimens. The HEL fibroblasts yielded 28 (72%) enteroviruses, followed by
      A549 (25 isolates, 64%), BGM (23 isolates, 59%) and RD cells (18 isolates, 46%).
      CONCLUSIONS: All isolates which grew in RD cells showed specific cytopathic
      effects in one or more of the other inoculated cell cultures. Quantitative
      determinations (TCID50) with five different enteroviruses showed that the HEL
      fibroblasts and RD cell line to be the most sensitive cell types, followed by BGM
      and A549 cell lines. However, integrity of the inoculated cell monolayers was
      best with HEL fibroblasts and A549 cells but morphology was not optimal with RD
      cells during the incubation period of 14 days.

PMID- 9784145
TI  - Usefulness of nested PCR and sequence analysis in a nosocomial outbreak of
      neonatal enterovirus infection.
AB  - BACKGROUND: Non-polio enterovirus infections are recognized in children during
      summer-fall seasons and they sometimes cause large outbreaks. We experienced a
      nosocomial infection in the neonatal nursery and echovirus type 7 was isolated
      from samples of four patients. OBJECTIVES: We diagnosed the horizontal infection
      of four neonates by reverse transcriptase-nested polymerase chain reaction (RT
      nested PCR) and the nucleotide sequence. STUDY DESIGN: Total RNA was extracted
      from clinical isolates, serum samples and cerebrospinal fluid (CSF). We amplified
      enterovirus genome in the 5'-noncoding region by nested PCR and determined the
      nucleotide sequences. RESULTS: Enterovirus genome was detected in all isolates,
      in the acute-phase sera in all four patients and in the CSF in one patient by the
      first PCR. By using nested PCR, the genome was detected from convalescent-phase
      sera in two patients. All enterovirus genome obtained from the nursery outbreak
      showed the same sequences with 100% homology. CONCLUSION: We demonstrated the
      clinical advantages of RT-nested PCR from serum samples and the analysis of
      nucleotide sequencing gave the supportive evidence of identification of
      transmission pathway.

PMID- 9784147
TI  - Predictors of positivity for hepatitis B and the derivation of a selective
      screening rule in a Canadian sexually transmitted disease clinic.
AB  - OBJECTIVES: To determine the prevalence of hepatitis B surface antibody (anti
      HBs) and antigenemia (HBsAg), the risk factors for seropositivity and the
      effectiveness of a selective serologic screening rule among sexually transmitted
      diseases (STD) clinic attendees. STUDY DESIGN: Clients in the Hamilton STD Clinic
      were surveyed from October 1992 to July 1993 on sociodemographic, past medical,
      and behavioural data, were tested for several STDs and were offered serological
      testing and vaccination against hepatitis B. Predictors of seropositivity were
      determined by single variable analysis. A selective serologic screening rule was
      derived using logistic regression modelling. RESULTS: The seroprevalence of anti
      HBs was 6.8% (21/310) in the 310 of 385 clients (80.5%) who agreed to be tested
      and interviewed. There were no HBsAg carriers. Five independent risk factors were
      identified by logistic regression: (1) age greater than 35 years; (2) birth
      outside Canada and histories of; (3) syphilis; (4) gonorrhoea; or (5) injection
      drug use. If clients with at least one of these predictors had been tested, 34.5%
      would have been selected for serologic testing and 85.7% of all positives would
      have been detected. The screening rule was more effective for men than for women.
      CONCLUSION: In this low prevalence setting, selecting STD clinic clients based on
      the presence of any one of five risk predictors appears to be an effective
      strategy for hepatitis B serologic screening in the context of a Canadian
      vaccination program.

PMID- 9784146
TI  - Development and use of nested polymerase chain reaction (PCR) for the detection
      of adenovirus from conjunctivitis specimens.
AB  - BACKGROUND: The standard virus isolation method for detecting adenovirus is time
      consuming and direct detection of viral antigens in smears has its limitations.
      Therefore a rapid and a reliable method to identify virus in clinical specimens
      is desirable. OBJECTIVE: To develop and evaluate nested PCR as a tool for
      detecting adenovirus from conjunctival swabs of patients with acute
      conjunctivitis during an epidemic. STUDY DESIGN: A total of 201 patients with
      acute conjunctivitis were seen between August and November 1996. Conjunctival
      swabs from the most recently affected eyes were collected from 20 random patients
      and processed for antigen detection in direct smears, for adenovirus, enterovirus
      (EV70) and coxsackievirus A24 variant and adenovirus isolation by culture. Nested
      PCR was performed using oligonucleotides to amplify 1004 basepair (bp) and 956 bp
      fragments of DNA coding for adenovirus hexon protein. The neutralisation test, to
      type the adenovirus, was done on four isolates selected at random. RESULTS: The
      PCR could detect 0.0032 fg of adenovirus DNA (corresponding to 8.3 x 10(-3)
      adenovirus particles). The EV70 and coxsackievirus A24 antigens were not
      detected. The specimens were positive for adenovirus by all three techniques in
      seven patients: (a) by direct smear and PCR in 2; (b) by virus isolation and PCR
      in 2; and (c) by PCR alone in five patients. In one patient the direct smear
      alone was positive. The PCR required 3 days to detect the virus, antigen
      detection provided diagnosis the same day and virus isolation required 8-27 days.
      A total of four isolates selected at random were identified as serotype 7a.
      CONCLUSION: The nested PCR is a reliable and rapid technique for detection of
      adenovirus from conjunctival swabs. The adenovirus serotype 7a was the likely
      causative agent of this epidemic conjunctivitis.

PMID- 9784148
TI  - Antimycobacterial activities of dehydrocostus lactone and its oxidation products.
AB  - In an attempt to study the structural dependence of antimycobacterial activity of
      the guaianolide dehydrocostus lactone and its derivatives, m-chloroperoxybenzoic
      acid oxidations of dehydrocostus lactone (1a) were performed. Three new
      monoepoxides, one previously synthesized diepoxide, and two new diepoxides were
      obtained. Two of the monoepoxides are C-10 epimers (3a, 3b), while the 4(15)
      monoepoxide (2) has the 4alpha-O-configuration. The known diepoxide (4a) contains
      a C-10 alpha-epoxide and a beta-epoxide at C-4. The diepoxides 4b and 4c, each
      with a C-4 alpha-epoxy group, differ in the configuration of the epoxide ring at
      C-10. Allylic oxidation of dehydrocostus lactone (1a) with selenium dioxide/tert
      butyl hydroperoxide afforded the known 3-epizaluzanin C (1b). The relative
      configurations of compounds 1b-4c were established by 1D and 2D NMR techniques
      (1H, 13C, COSY, NOESY, HMQC, and HMBC) as well as comparison with literature
      data. The molecular structures of lactones 1b, 4a, and 4c were determined by
      single-crystal X-ray diffraction. In radiorespirometric bioassays against
      Mycobacterium tuberculosis and Mycobacterium avium, dehydrocostus lactone (1a)
      exhibited minimum inhibitory concentrations of 2 and 16 microgram/mL,
      respectively. In contrast, its monoepoxides (2, 3a, and 3b) and diepoxides (4a
      c), as well as its hydrogenated derivatives and other analogues (1b, 1c, 5, and
      6), showed significantly lower activities against M. tuberculosis.

PMID- 9784150
TI  - Tannins, flavonol sulfonates, and a norlignan from phyllanthus virgatus 
AB  - Investigation of the constituents of Phyllanthus virgatus has led to the
      isolation of five new compounds, including a norlignan, 2-(3, 4
      methylenedioxybenzyl)-4-(3,4-methylenedioxyphenyl)-3-butyne-1, 2-diol named
      virgatyne (1); a hydrolyzable tannin, virganin (2); and three flavonoid
      sulfonates, galangin-8-sulfonate (4), galangin-3-O-beta-D-glucoside-8-sulfonate
      (5), and kaempferol-8-sulfonate (6). Their structures were established by
      spectral and chemical methods.

PMID- 9784151
TI  - Diterpene polyesters from euphorbia seguieriana 
AB  - An Me2CO extract of Euphorbia seguieriana (Euphorbiaceae) afforded seven new
      diterpene polyesters (1-7). Five of them (1-5), having a new parent alcohol that
      was named 17-hydroxymyrsinol, were structurally related to myrsinol. The other
      two compounds (6, 7) were new derivatives of the known parent alcohols
      cyclomyrsinol and lathyrane. The structure elucidations of the new compounds by
      highfield spectroscopic methods, including 1D and 2D NMR techniques, are
      described.

PMID- 9784149
TI  - Antitubercular natural products: berberine from the roots of commercial Hydrastis
      canadensis powder. Isolation of inactive 8-oxotetrahydrothalifendine, canadine,
      beta-hydrastine, and two new quinic acid esters, hycandinic acid esters-1 and -2.
AB  - Berberine (4) is responsible for the activity of an extract of a commercial root
      sample of Hydrastis canadensis against multiply drug resistant Mycobacterium
      tuberculosis. Two new quinic acid feruloyl esters, compounds 2 and 3, have been
      isolated from the same source along with canadine (1c), 8
      oxotetrahydrothalifendine (1), and beta-hydrastine (5). These were found to be
      inactive. The structures of the new compounds were elucidated from spectral (1H,
      13C, HMQC, HMBC, and H-H COSY) and chemical evidences.

PMID- 9784152
TI  - DNA-damaging steroidal alkaloids from Eclipta alba from the suriname rainforest1.
AB  - Bioassay-guided fractionation of the MeOH extract of Eclipta alba using three
      yeast strains (1138, 1140, and 1353) resulted in the isolation of eight bioactive
      steroidal alkaloids (1-8), six of which are reported for the first time from
      nature. The major alkaloid was identified as (20S)(25S)-22,26-imino-cholesta
      5,22(N)-dien-3beta-ol (verazine, 3), while the new alkaloids were identified as
      20-epi-3-dehydroxy-3-oxo-5,6-dihydro-4,5-dehydroverazine (1), ecliptalbine [(20R)
      20-pyridyl-cholesta-5-ene-3beta,23-diol] (4), (20R)-4beta-hydroxyverazine (5),
      4beta-hydroxyverazine (6), (20R)-25beta-hydroxyverazine (7), and 25beta
      hydroxyverazine (8). Ecliptalbine (4), in which the 22,26-imino ring of verazine
      was replaced by a 3-hydroxypyridine moiety, had comparable bioactivity to
      verazine in these assays, while a second alkaloid (8) showed good activity
      against Candida albicans. All the alkaloids showed weak cytotoxicity against the
      M-109 cell line.

PMID- 9784153
TI  - Growth-inhibitory activities of benzofuran and chromene derivatives toward
      Tenebrio molitor.
AB  - Growth-inhibitory activities of selected natural benzofurans (4-9), trans
      cinnamic acid derivatives (10-13), chromene compounds (14 and 16), and some
      semisynthetic derivatives were determined in last instar larvae of Tenebrio
      molitor via topical administration in Me2CO. The most inhibitory of the tested
      compounds were 3-gamma, gamma-dimethylallyl-p-coumaric acid (10) and the
      benzofuran derivative 12-(p-cumaroyloxy)-tremetone (5), the former compound
      acting on the pupae and the latter on the last instar larvae. Several
      developmental deficiencies were observed, and some structure-activity
      relationships are discussed.

PMID- 9784155
TI  - Isolation, total synthesis, and relative stereochemistry of a dihydrofurocoumarin
      from dorstenia contrajerva 
AB  - The roots of Dorstenia contrajerva afforded the dihydrofurocoumarin 1b whose
      identity was determined from NMR spectral data of the derived acetate 7b combined
      with the total syntheses of 1a and 1b, which were carried out in five steps with
      19% overall yield, starting from 2,3-dihydro-2-isopropenyl-6-methoxybenzofuran
      (2). The relative stereochemistry of 7b was determined from a single-crystal X
      ray diffraction study as (2S,1'S)-2, 3-dihydro-2-(1'-hydroxy-1'
      acetyloxymethylethyl)-7H-furo[3, 2g][1]benzopyran-7-one.

PMID- 9784154
TI  - Ursolic acid from Plantago major, a selective inhibitor of cyclooxygenase-2
      catalyzed prostaglandin biosynthesis.
AB  - A hexane extract of Plantago major was investigated by bioactivity-directed
      fractionation, using an in vitro cyclooxygenase-2 (COX-2) catalyzed prostaglandin
      biosynthesis inhibition assay, and resulted in the isolation of ursolic acid (1).
      This triterpenoid showed a significant COX-2 inhibitory effect, directly on the
      enzyme activity, with an IC50 value of 130 microM and a COX-2/COX-1 selectivity
      ratio of 0.6. The structural isomer oleanolic acid (2) was found to be less
      active than 1, with an IC50 value of 295 microM, but showed a similar selectivity
      ratio (0.8). Furthermore, no significant inhibition on COX-2 or COX-1 was
      observed by the triterpenoid, 18beta-glycyrrhetinic acid (3). The direct
      inhibitory effect of 1 and 2 on COX-2 catalyzed prostaglandin biosynthesis
      increased with preincubation, indicating a time-dependent inhibition, while the
      effect on COX-1 was found to be independent of preincubation time.

PMID- 9784156
TI  - Isolation, structure determination, and biological activity of dolastatin 12 and
      lyngbyastatin 1 from Lyngbya majuscula/Schizothrix calcicola cyanobacterial
      assemblages.
AB  - Lyngbyastatin 1 (1a), a new cytotoxic analogue of dolastatins 12 (2a) and 11 (4),
      was isolated as an inseparable mixture with its C-15 epimer (1b) from extracts of
      a Lyngbya majuscula/Schizothrix calcicola assemblage and a L. majuscula strain
      collected near Guam. Dolastatin 12 (2a) was also encountered as an inseparable
      mixture with its C-15 epimer (2b) in L. majuscula/S. calcicola assemblages. At
      least one of the compounds in each mixture appeared to exist in solution as a
      mixture of slowly interconverting conformers resulting in broadened signals in 1H
      NMR spectra. Structure elucidation therefore relied principally on mass
      spectroscopy and chemical degradation studies. Both 1ab and 2ab proved toxic with
      only marginal or no antitumor activity when tested against colon adenocarcinoma
      #38 or mammary adenocarcinoma #16/C. Both 1ab and 2ab were shown to be potent
      disrupters of cellular microfilament networks.

PMID- 9784157
TI  - New diketopiperazines from the sponge Dysidea chlorea.
AB  - Twelve new polychlorinated diketopiperazines (7-18), along with six known ones (1
      6) and a known sterol (19), were isolated from the sponge Dysidea chlorea,
      collected from Yap, Federated States of Micronesia. The structures of dysamides I
      T (7-18) were elucidated by spectroscopic methods, and one (8) was confirmed by
      chemical conversion. The stereochemistry of the dysamides is discussed.

PMID- 9784158
TI  - Halawanones A-D, new polycyclic quinones from a marine-derived streptomycete 
AB  - Four new quinone-containing metabolites, halawanones A-D (1-4), have been
      isolated along with the known compound nanaomycin D (5) from liquid cultures of a
      streptomycete obtained from a sediment sample collected in the estuarine
      environment at the mouth of Halawa stream, Oahu. The structures of the new
      compounds were determined through the interpretation of spectral data. The
      absolute stereochemistries were determined using a combination of CD and NMR.

PMID- 9784159
TI  - Microbiological transformation of manoyl oxide derivatives by Mucor plumbeus.
AB  - Biotransformations of jhanol (18-hydroxymanoyl oxide) (2), jhanidiol (1beta,18
      dihydroxymanoyl oxide) (3), and 1-oxo-jhanol (1-oxo-18-hydroxymanoyl oxide) (4)
      by the fungus Mucor plumbeus have been studied. In the incubation of 2 there
      exists a preference for hydroxylation at C-2(alpha) (8) and C-6(beta) (9-11) and,
      to a lesser degree, at C-1(alpha) (7), C-11(alpha) (6), and C-11(beta) (5 and
      10). In the second substrate (3), the presence of a 1beta-hydroxyl group inhibits
      6beta- or 11-hydroxylation. Epoxidation of the vinyl group constitutes the main
      reaction, with the positions 2alpha (14) and 3beta (15) being hydroxylated. In
      the incubation of 4, there was a preference for 6beta-hydroxylation (21) or
      epoxidation of the vinyl group (22). Other hydroxylations observed were at the
      2alpha (19), 2beta (20), 3alpha (23), 3beta (24), and 11beta (18) positions.

PMID- 9784160
TI  - Neoclerodane diterpenoids from teucrium massiliense 
AB  - A reinvestigation of the diterpene metabolites of Teucrium massiliense L. allowed
      the isolation of four new neoclerodane derivatives, teumassilenins A-D, together
      with all the diterpenoids previously reported as constituents of this plant. The
      structures of the new compounds (1-4) were established by chemical and
      spectroscopic means. A plausible biogenetic relationship between several of these
      substances is briefly discussed, and some unpublished physical and spectroscopic
      data of the previously known diterpenoid teumassin (5) are now reported.

PMID- 9784161
TI  - Tenuecyclamides A-D, cyclic hexapeptides from the cyanobacterium Nostoc
      spongiaeforme var. tenue.
AB  - Four modified cyclic hexapeptides, tenuecyclamides A-D (1-4), were isolated along
      with the known antibiotic, borophycin (5), from the methanol extract of Nostoc
      spongiaeforme var. tenue (TAU strain IL-184-6). The planar structure of
      tenuecyclamides A-D (1-4) was determined by homonuclear and inverse-heteronuclear
      2D-NMR techniques as well as by high-resolution mass spectrometry measurements.
      The absolute configuration of the asymmetric centers was studied by Marfey's
      method for HPLC. The stereochemistry of the asymmetric centers in tenuecyclamides
      A and B (1 and 2) could not be fully determined, while that of tenuecyclamides C
      and D (3 and 4) was unambiguously determined.

PMID- 9784162
TI  - Pyranocoumarins from tropical species of the genus Calophyllum: a chemotaxonomic
      study of extracts in the National Cancer Institute collection.
AB  - (+)-Calanolide A, a novel dipyranocoumarin from the Malesian tree Calophyllum
      lanigerum var. austrocoriaceum, and a closely related compound, (-)-calanolide B,
      isolated from Calophyllum teysmannii var. inophylloide, are representatives of a
      distinct class of nonnucleoside HIV-1 specific reverse-transcriptase inhibitor
      under development as an AIDS chemotherapeutic. NCI repository specimens totalling
      315 organic extracts from 31 taxa of Calophyllum were analyzed for related
      pyranocoumarins using a simple TLC system. A total of 127 extracts was initially
      classified as "positive"; eight out of the 31 taxa examined, representing perhaps
      28 species already described (1/7-1/8 of all the species in this genus),
      contained prenylated coumarins, suggesting that these compounds, while sometimes
      abundantly present, are not widespread in the genus. Representative members of
      the TLC-positive extracts were partitioned between CH2C12 and 25% aqueous MeOH;
      the CH2C12-soluble materials were then analyzed by TLC and 1H NMR to confirm the
      presence of pyranocoumarins. The anti-HIV activity of the partitioned extracts
      are also presented. This study suggested that there are several distinctive
      coumarin chemotaxonomic markers distinguishing species of this genus.

PMID- 9784165
TI  - Five new polyacetylenes from a sponge of the genus petrosia 
AB  - Petrocortynes D-H, novel C46 polyacetylenes, were isolated from a sponge of the
      genus Petrosia collected from Keomun Island, Korea. Petrocortyne D (2) is a 4,5
      dihydro derivative of a diastereomer of petrocortyne A (1), and petrocortynes E-H
      (3-6) possess an additional allylic-hydroxyl group. The structures of these
      compounds were determined by combined chemical and spectral methods, and absolute
      configurations of most of the asymmetric carbon centers were determined by the
      modified Mosher's method. Limitations on the application of Mosher's method to
      allylic alcohols is discussed. Petrocortynes D-H exhibited moderate cytotoxicity
      and inhibitory activity against PLA2.

PMID- 9784163
TI  - Activity-guided isolation of steroidal alkaloid antiestrogen-binding site
      inhibitors from Pachysandra procumbens.
AB  - Four novel steroidal alkaloids, (+)-(20S)-20-(dimethylamino)-3-(3'alpha
      isopropyl)-lactam-5alpha-+ ++preg n-2-en-4-one (1), (+)-(20S)-20-(dimethylamino)
      16alpha-hydroxy-3-(3'alpha-isopropyl) -la ctam-5alpha-pregn-2-en-4-one (2), (+)
      (20S)-3-(benzoylamino)-20-(dimethylamino)-5alpha-pregn-2-en-++ +4beta -yl acetate
      (3), and (+)-(20S)-2alpha-hydroxy-20-(dimethylamino)-3beta-phthalimido-5 alpha-
      pregnan-4beta-yl acetate (4), as well as five known compounds, (-)-pachyaximine A
      (5), (+)-spiropachysine (6), (+)-axillaridine A (7), (+)-epipachysamine D (8),
      and (+)-pachysamine B (9), were isolated from Pachysandra procumbens, using a
      bioassay-guided fractionation based on inhibition of 3H-tamoxifen binding at the
      antiestrogen binding site (AEBS). Compounds 1-7 and 9 demonstrated significant
      activity as AEBS-inhibitory agents, and compounds 3, 5 and 9 were found to
      potentiate significantly the antiestrogenic effect mediated by tamoxifen in
      cultured Ishikawa cells. The structure elucidation of compounds 1-4 was carried
      out by spectral data interpretation.

PMID- 9784164
TI  - Revision of the structure of fagaridine based on the comparison of UV and NMR
      data of synthetic compounds.
AB  - Fagaridine is a quaternary benzo[c]phenanthridine alkaloid, originally isolated
      from Fagara xanthoxyloides in 1973. The assigned structure of this alkaloid was 7
      hydroxy-8-methoxy-5-methyl-2, 3-(methylenedioxy)benzo[c]phenanthridinium (1). We
      have synthesized this compound, coded NK109, aiming at a practical antitumor
      drug, and during synthetic studies we questioned the original assigned structure.
      Thus, we synthesized 8-hydroxy-7-methoxy-5-methyl-2, 3
      (methylenedioxy)benzo[c]phenanthridinium (2), isomer of the assigned structure,
      and compared the spectroscopic data of both 1 and 2. The NMR data of 1 and 2 were
      very similar, but the UV spectra were completely different. The UV data for
      fagaridine agreed with these for 2; consequently, the true structure of
      fagaridine is 2, not 1.

PMID- 9784166
TI  - Munchiwarin, a prenylated chalcone from crotalaria trifoliastrum 
AB  - Munchiwarin, a chalcone with the first 2,2, 6-tri-isoprenyl-cyclohex-5-ene-1,3
      dione skeleton, was isolated from Crotalaria trifoliastrum and structurally
      identified by various NMR techniques in combination with X-ray crystallography.

PMID- 9784167
TI  - Dihydroramulosin from Botrytis sp.
AB  - Botrytis sp., isolated from the inner bark of the Pacific yew, Taxus brevifolia,
      was shown to produce ramulosin (1), 6-hydroxyramulosin (2), and the new compound
      8-dihydroramulosin (3). The structure of dihydroramulosin was deduced from the
      NMR spectra and confirmed by chemical conversion from ramulosin.

PMID- 9784169
TI  - Total synthesis of (R,S)-sophoraflavanone C 
AB  - Sophoraflavanone C, a C-8 geranylflavanone natural product originally isolated
      from Echinosophora koreensis, has been synthesized in racemic form in six steps,
      starting from 2,4, 6-trihydroxyacetophenone and 2,4-dihydroxybenzaldehyde.

PMID- 9784168
TI  - Aculeoside B, a new bisdesmosidic spirostanol saponin from the underground parts
      of Ruscus aculeatus.
AB  - From the underground parts of Ruscus aculeatus, a new bisdesmosidic spirostanol
      saponin named aculeosides B (2) was isolated, and its structure was determined on
      the basis of spectroscopic analysis, including 2D NMR techniques. Aculeoside A
      (1), which was previously isolated from the same plant source, exhibited
      inhibitory activity on cell growth of leukemia HL-60 cells with an IC50 value of
      0.48 microgram mL(-1), while aculeoside B (2) was inactive.

PMID- 9784170
TI  - Bebryazulene, a new guaiane metabolite from the indian ocean gorgonian coral,
      bebryce grandicalyx 
AB  - Bebryazulene (1), a new sesquiterpene having the guaiane skeleton, was isolated
      from the methanol-chloroform 1:2 extract of the Indian Ocean gorgonian coral
      Bebryce grandicalyx (Kuekenthal) collected in the lagoon of Mayotte. Structure
      assignment was based on interpretation of spectroscopic data. This new metabolite
      was very labile and reacted with 4-phenyl-3H-1,2,4-triazoline-3,5-dione to yield
      an unexpected adduct.

PMID- 9784171
TI  - Callosine, a 3-alkyl-substituted pyrrolizidine alkaloid from senecio callosus 
AB  - Two collections of Senecio callosus from different regions of Mexico contained a
      structural diversity of pyrrolizidine alkaloids (PAs), which may contribute to
      the easy adaptation of this species. In addition to some known compounds, two new
      PAs (1 and 2) were isolated, and their structures were established by chemical
      transformations and spectroscopic studies.

PMID- 9784172
TI  - Two acylated diarylheptanoid glycosides from red alder bark 
AB  - Two novel acylated diarylheptanoid glycosides, oregonosides A and B (3, 4,
      respectively), were isolated from red alder bark and their structures established
      by spectrometric techniques. The compounds were identified as (5S)-1,7-bis(3, 4
      dihydroxyphenyl)-5-O-(6-O-benzoyl-beta-D-glucopyranosyl)-heptan-3-o ne and (5S)
      1,7-bis(3, 4-dihydroxyphenyl)-5-O-(6-O-vanilloyl-beta-D-glucopyranosyl)-heptan-3 
      one.

PMID- 9784173
TI  - New iridoids from the medicinal plant Barleria prionitis with potent activity
      against respiratory syncytial virus.
AB  - Two new iridoid glycosides (1 and 2), together with the known compounds barlerin
      (3) and verbascoside (4), were isolated from Barleria prionitis. The new iridoid
      glycosides were determined to be 6-O-trans-p-coumaroyl-8-O-acetylshanzhiside
      methyl ester (1) and its cis isomer (2) by using spectroscopic, especially 2D
      NMR, data. A 3:1 mixture of 1 and 2 was shown to have potent in vitro activity
      against respiratory syncytial virus (EC50 2.46 microgram/mL, IC50 42.2
      microgram/mL).

PMID- 9784174
TI  - A stilbene from the roots of leuzea carthamoides 
AB  - From the roots of Leuzea carthamoides, (E)-3,3'-dimethoxy-4, 4'-dihydroxystilbene
      (1) has been isolated and its structure elucidated by means of NMR spectroscopy,
      including HMQC and HMBC measurements, mass spectrometry, and X-ray
      crystallography.

PMID- 9784175
TI  - Two new diterpene glycosides from the soft coral lemnalia bournei 
AB  - Two new bicyclic diterpene glycosides, lemnaboursides B and C (1, 2), have been
      isolated from the Chinese soft coral Lemnalia bournei. They are the monoacetate
      derivatives of lemnabourside (3) previously obtained from the same species. The
      structures of compounds 1 and 2, which showed weak cytotoxicity against HepA,
      S180A and EAC cells, respectively, were established from spectral data and
      chemical transformations.

PMID- 9784176
TI  - Debromosceptrin, an alkaloid from the Caribbean sponge Agelas conifera.
AB  - As the result of a structurally guided isolation to identify lead compounds for
      the treatment of opportunistic infections of AIDS, the dihydrochloride salt of a
      new symmetrical pyrrole dimer debromosceptrin (1), and two known pyrrole
      analogues (2 and 3) were isolated from the Caribbean sponge Agelas
      coniferacollected from Belize. The structure of debromosceptrin was identified by
      analysis of spectral data. 15N spectral data assignments were made for compounds
      1-3. Compounds 2 and 3 showed marginal inhibition of Mycobacterium tuberculosis.

PMID- 9784177
TI  - Isolation of a nitrile-containing indole alkaloid from the terrestrial blue-green
      alga hapalosiphon delicatulus 
AB  - Ambiguine G nitrile is a new indole alkaloid from the terrestrial blue-green alga
      Hapalosiphon delicatulus (UH isolate IC-13-1). It is the first nitrile to be
      found in the Stigonemataceae.

PMID- 9784178
TI  - Abietane diterpenoids from the cones of larix kaempferi 
AB  - Three new abietane-type diterpenes, 7alpha,15-dihydroxyabieta-8,11, 13-trien-18
      al (1); 15,18-dihydroxyabieta-8,11,13-trien-7-one (2); and 18-nor-4,15
      dihydroxyabieta-8,11,13-trien-7-one (3), were isolated from the cones of Larix
      kaempferi, together with three known diterpenes, abieta-8,11,13-trien-18-yl
      succinate, 16-nor-15-oxoabieta-8,11,13-trien-18-oic acid, and 7beta-hydroxyabieta
      8,11,13-trien-18-oic acid. The structures of 1-3 were determined on the basis of
      chemical and spectral evidence.

PMID- 9784179
TI  - New alkaloids from the papua new guinean sponge agelas nakamurai 
AB  - Two new bromopyrroles and a new diterpene possessing a 9-methyladenium moiety
      have been isolated from the Papua New Guinean sponge Agelas nakamurai Hoshino.

PMID- 9784180
TI  - Biotransformation of resveratrol to piceid by Bacillus cereus.
AB  - Microbial transformation of resveratrol (1), trans-3,4', 5-trihydroxystilbene,
      was studied. Preparative scale biotransformation of 1 with whole-cell suspensions
      of Bacillus cereus UI 1477 resulted in the production of metabolite 2 which was
      identical in all respects to an authentic sample of piceid, resveratrol 3-O-beta
      D-glucoside.

PMID- 9784181
TI  - Extraction and quantification of daidzein and genistein in food.
AB  - A simple analytical method has been developed for routine quantification of a
      broad range of concentrations of the isoflavones daidzein and genistein in food.
      The synthetic glucosides daidzin and genistin were used as internal standards,
      combined with each food prior to extraction. The recovery of the aglycones
      daidzein and genistein from these internal standards were used to ensure the
      completeness of the extraction and aid quantification of isoflavones from the
      food. Hydrolytic enzymes from Aspergillus niger were used, in aqueous buffer, to
      liberate daidzein and genistein from their respective glycosides. The aglycone
      isoflavones were partitioned from the aqueous buffer into ethyl acetate. After
      evaporation of the ethyl acetate under nitrogen, the isoflavones were derivatized
      with N-tert-(butyldimethylsilyl)-N-methyltrifluoroacetamide and quantified by
      comparison with authentic synthetic standards using gas chromatography-mass
      spectrometry in selected ion mode. The isoflavone content of a stock soy flour
      was determined, using 36 separate assays, to be 1.05 mg daidzein and 1.11 mg
      genistein per gram of freeze-dried food, and the interassay coefficient of
      variation was 2.7 and 4.7, respectively.

PMID- 9784182
TI  - A novel method for determining kinetic parameters of dissociating enzyme systems.
AB  - The theoretical analysis has been presented for the kinetics of dissociating
      associating enzyme-catalyzed reactions. On the basis of the kinetic equation of
      substrate reaction, a general procedure is developed for determining the kinetic
      constants of dissociating-associating enzyme reactions. By analyzing the
      experimental data of initial velocity and steady-state velocity as functions of
      enzyme and substrate concentration, all unknown kinetic parameters can be
      determined from several simple, sequential calculations. This method is simple
      and rigorous, and the required experiments may also not be difficult for most
      dissociating enzyme systems. Therefore, the present method should be a useful
      addition to the available methods for studying subunit dissociation of enzymes.
      In comparison to other physical methods, the advantage of this method is not only
      its usefulness in the study of self-associating reactions at very low protein
      concentration but its convenience in the study of substrate effects on subunit
      subunit interactions.

PMID- 9784183
TI  - Immobilized nicotinic receptor stationary phase for on-line liquid
      chromatographic determination of drug-receptor affinities.
AB  - Nicotinic acetylcholine receptors (nAChR) are ligand-gated ion channels which
      mediate nicotinic cholinergic transmission in the nervous system. A nAChR subtype
      composed of alpha3 and beta4 subunits (alpha3/beta4 subtype), prepared from a
      stably transfected KXalpha3beta4R2 cell line, has been immobilized in the
      phospholipid monolayer of an immobilized artificial membrane (IAM) liquid
      chromatography (LC) stationary phase. Approximately 60 mg of protein was
      immobilized per gram IAM particles. The resulting phase was used for the rapid on
      line chromatographic determination of drug binding affinities to nAChRs. Relative
      binding affinities were determined by frontal chromatography for (+/-)
      epibatidine (Kd: 0.27 +/- 0.05 nM) > A85380 (Kd: 17.2 +/- 0.5 nM) > (-)-nicotine
      (Kd: 88 +/- 33 nM) > carbachol (Kd: 1280 +/- 30 nM) > atropine (Kd: 14,570 +/-
      2600 nM). These results are consistent with the affinity rank order obtained from
      binding assays using membrane homogenates. The immobilized receptor LC stationary
      phase was stable and reproducible. This approach opens up the possibility of the
      production of a variety of immobilized receptor LC stationary phases which may be
      used for direct determination of drug-receptor binding interactions and for the
      rapid on-line screening of combinatorial pools for drug candidates.

PMID- 9784184
TI  - A fluorescence-based assay for ribonuclease A activity.
AB  - A sensitive assay for ribonuclease A activity based on the relief of fluorescence
      quenching within a defined oligomeric substrate (5' fluorescein-AAAArUAAAA-3'
      rhodamine) is described. The substrate can be produced using an automated nucleic
      acid synthesizer and commercially available reagents. Together with a
      nonfluorescent cosubstrate (5'-dimethoxytrityl-AAAArUAAAA), the compound can be
      used to determine kinetic constants for the first step (transphosphorylation) of
      the ribonuclease-catalyzed reaction. These measurements should be useful for
      structure-based analyses of ribonuclease activity since a crystal structure has
      been determined for a closely analogous enzyme-inhibitor complex.

PMID- 9784185
TI  - Construction and use of a detergent-sensitive electrode to measure dodecyl
      sulfate activity and binding.
AB  - We describe the construction and use of a dodecyl sulfate-sensitive electrode
      cell to measure the activity of the detergent in biological samples. The
      electrode is based on the incorporation of a cetyltrimethylammonium/dodecyl
      sulfate complex in a siloxane polymer membrane. The cell records changes in the
      activity of SDS from 10(-6) to 10(-5) M SDS up to the critical micellar
      concentration. In aqueous solutions the cell follows Nernst' law with an
      electrometric response which is not affected by protein per se, but is modified
      by supporting electrolytes like NaCl. We demonstrate by comparison with
      equilibrium dialysis that the electrode can be used both to detect the high
      affinity binding sites of serum albumin for SDS and to follow cooperative binding
      of the detergent to serum albumin, ovalbumin, and beta-lactoglobulin in the
      concentration interval 10(-4)-10(-3) M of unbound SDS. We conclude that the
      electrode has properties which should enable its use to monitor changes in SDS
      activity during interaction with biological material. The electrode may also be
      used to measure the activity of other detergents which, like SDS, form a
      sparingly soluble complex with cetyltrimethylammonium bromide.

PMID- 9784186
TI  - Muramyl peptide probes derived from tracheal cytotoxin of Bordetella pertussis.
AB  - A novel semisynthetic scheme was developed to couple amine-reactive labeling
      reagents to the muramyl peptide tracheal cytotoxin (TCT) without affecting a
      critical amine group. Tracheal cytotoxin, N-acetylglucosaminyl-1, 6-anhydro-N
      acetylmuramyl-Ala-gamma-Glu-A2pmAla (A2pm, diaminopimelic acid), is released by
      Bordetella pertussis, the etiologic agent of whooping cough. This glycopeptide
      reproduces the specific ciliated cell damage observed in the respiratory tract
      during B. pertussis infection. To examine binding of TCT to target respiratory
      cells, we have produced labeled TCT analogs. Structure-function studies have
      shown that the primary amine of the A2pm side chain is essential for TCT toxicity
      in respiratory tissue. The methodology described here allows coupling of amine
      reactive reagents to TCT without affecting this essential amine. The terminal N
      acetylglucosamine ring is opened by oxidation with periodic acid, a dihydrazide
      linker is coupled to the oxidized ring, and pH control is used to selectively
      derivatize the free hydrazide with an N-hydroxysuccinimide ester, while the A2pm
      side-chain amine remains free. Using this method, we have coupled the Bolton
      Hunter reagent to TCT, producing a biologically active 125I-labeled TCT analog.

PMID- 9784187
TI  - Development of a chemiluminescent urease activity assay for Helicobacter pylori
      infection diagnosis in gastric mucosa biopsies.
AB  - A chemiluminescent urease activity assay has been developed and optimized using
      the chemiluminescent pH indicator phthalhydrazidylazoacetylacetone. This compound
      is stable at pH </= 7 and decomposes at higher pH values, emitting light in the
      presence of H2O2. Urease catalyzes hydrolysis of urea to form NH3 and CO2 which
      increase the pH of the reaction medium, thus allowing the chemiluminescent
      indicator to decompose and produce photons. The emitted light is proportional to
      the urease activity when urea is in excess. Urease tests based on colorimetric pH
      indicators like phenol red are commercially available and commonly used for the
      rapid diagnosis of Helicobacter pylori infection in gastric mucosa biopsy
      specimens, since this bacterium produces high amounts of urease. Such
      colorimetric tests often lack sensitivity, giving false-negative results. The
      developed chemiluminescent test proved to be at least 50-fold more sensitive than
      the colorimetric tests, permitting early diagnosis of infection, and it is more
      rapid, giving results in 1-10 min compared to 30 min. Further applications of
      this assay could be the in situ localization of urease activity, corresponding to
      the presence of H. pylori, in gastric mucosa cryosections and the development of
      high-throughput screening assays of antimicrobial drugs able to inactivate the
      bacterium.

PMID- 9784188
TI  - Analysis of recombinant human ADP-ribosylation factors by reversed-phase high
      performance liquid chromatography and electrospray mass spectrometry.
AB  - Two complementary approaches utilizing reverse-phase high-performance liquid
      chromatography and liquid chromatography/mass spectrometry were developed to
      analyze recombinantly produced Group I and Group II human ADP-ribosylation
      factors (ARFs). We observe that the NH2 termini of Group II ARFs (ARF4 and ARF5)
      are efficiently processed by removal of the initiating methionine. In contrast,
      the NH2 termini of Group I ARFs (ARF1 and ARF3), although fully deformylated,
      undergo only partial methionine cleavage. This result is unexpected as ARFs are
      canonical substrates for methionine processing in both bacterial and eukaryotic
      systems, but it may explain the difficulties encountered by many researchers
      attempting to produce myristoylated ARFs in Escherichia coli. Additionally, we
      observe that a significant fraction of purified ARF4 contains a modification
      which we demonstrate to be consistent with mono-glutathionation. Both methionine
      retention and glutathione modification may impact ARF function and the methods
      presented here should be employed to determine the quality of recombinant ARFs.

PMID- 9784189
TI  - Analysis of 2-aminobenzamide-labeled oligosaccharides by high-pH anion-exchange
      chromatography with fluorometric detection.
AB  - To establish high-pH anion-exchange chromatography with fluorometric detection
      (HPAEC-FD) for the sensitive oligosaccharide analysis, the system for HPAEC with
      pulsed amperometric detection (PAD) was modified by placing the anion
      micromembrane suppressor between PAD and fluoromonitor to neutralize the alkaline
      eluate and connecting the flow path. N-Linked oligosaccharides were released from
      various glycoproteins by hydrazinolysis followed by labeling with 2
      aminobenzamide, and their asialooligosaccharides were analyzed by HPAEC-FD using
      an isocratic elution with 0.3 M NaOH solution. The results indicated that the new
      system using FD offers fine separation of oligosaccharides at the subpicomole
      level. Coinjection of reduced dextran oligomers as internal standards which are
      detected by PAD permits us to express elution positions of the fluorescent
      oligosaccharides as glucose units, resulting in a much more reliable analysis.
      The system was also effectively used for structural analysis of oligosaccharides
      by sequential glycosidase digestion. Thus, HPAEC-FD promises to be an alternative
      tool for the sensitive analysis of oligosaccharides.

PMID- 9784190
TI  - Separation of radiolabeled orthophosphate and adenosine 5'-triphosphate by 20%
      polyacrylamide gel electrophoresis: an assay for brain microsomal Mg2+/Ca2+
      ATPase activity.
AB  - Measuring orthophosphate is an important tool in biochemical analyses used to
      study membrane transport ATPases essential for calcium homeostasis. Current
      techniques involve extraction of radioactive phosphate with organic solvents, a
      technique that results in large quantities of hazardous radioactive waste. Other
      colorimetric assays are less sensitive and are complicated by interference of
      background absorbance from membrane tissue and unutilized ATP. This report
      describes a unique assay for the detection of inorganic phosphate and its
      application to the study of rat brain microsomal Mg2+/Ca2+ ATPase from a membrane
      fraction. The technique involves the separation of radioactive phosphate from
      unused gamma-radiolabeled ATP by resolution on 20% polyacrylamide gels. Both are
      visualized with X-ray film and quantitated by liquid scintillation counting after
      extraction from the gels. The assay can detect as little as 4.1 pmol of
      radiolabeled ATP and ATPase activity in 3.5 ng/microliter of membrane protein.
      This method offers the advantage of simultaneous quantitation of radiolabeled ATP
      and radioactive orthophosphate without the generation of large quantities of
      radioactive waste. The results demonstrate the development of a novel assay
      procedure for quantitating orthophosphate that is extremely sensitive,
      reproducible, and applicable to the study of any phosphate liberating enzyme.

PMID- 9784191
TI  - Determination of glutamate by high-performance liquid chromatography with
      fluorescence detection in superfusates of rat brain preparations.
AB  - A method is described for the determination of glutamate in superfusates of
      cortical or hippocampal rat brain slices. This method is based on the precolumn
      derivatization of amino acids with orthopthaldialdehyde and mercaptopropionic
      acid, separation by high-performance liquid chromatography, and detection by
      fluorescence. By adjusting the concentrations of reagents and with the minimum
      dilution of the sample, it was possible to reproducibly measure the Ca2+
      dependent K+-evoked release of neurotransmitter glutamate in superfusates of
      brain slices.

PMID- 9784193
TI  - Simultaneous measurement of foliar glutathione, gamma-glutamylcysteine, and amino
      acids by high-performance liquid chromatography: comparison with two other assay
      methods for glutathione.
AB  - The recent production of transformed plants with enhanced capacity for
      glutathione synthesis has highlighted the interactions between foliar glutathione
      and turnover of free amino acid pools. The development of a convenient method for
      simultaneous measurement of glutathione, gamma-glutamylcysteine, and 16 amino
      acids is reported. This method utilizes derivatization of compounds with o
      phthalaldehyde in the presence of 2-mercaptoethanol followed by separation using
      reversed-phase high-performance liquid chromatography. Eluted compounds are
      detected fluorimetrically. The method was tested using untransformed poplars and
      poplars in which foliar thiol contents have been enhanced by overexpression of
      gamma-glutamylcysteine synthetase. Foliar contents of glutathione determined by
      this method were comparable to those measured in common extracts by two other
      techniques.

PMID- 9784192
TI  - The maltose-binding protein as a scaffold for monovalent display of peptides
      derived from phage libraries.
AB  - Random peptide libraries are displayed on filamentous bacteriophage as fusions to
      either the minor coat protein, pIII, or the major coat protein, pVIII. We have
      devised a means of isolating the peptide displayed on a phage clone by
      transferring it to the N-terminus of the maltose-binding protein (MBP) of
      Escherichia coli encoded by malE. Transfer of a peptide sequence to monomeric MBP
      eliminates phage-encoded amino acids downstream of the insert peptide as well as
      avidity effects caused by multivalent display on phage. Peptide:MBP fusions are
      also easily affinity purified on amylose columns. The pMal-p2 vector was
      engineered to accept phage DNA encoding pIII- and pVIII-displayed peptides fused
      to their respective leader sequences. Both types of leader sequence were shown to
      target the peptide:MBP fusions to the periplasm of E. coli. A streamlined
      procedure for transferring peptides to MBP was applied to clones that had been
      isolated from a panel of pVIII-displayed peptide libraries by screening with an
      HIV-1-specific monoclonal antibody (Ab). By enzyme-linked immunosorbent assay,
      the Ab bound each of the peptide:MBP fusions and required the presence of a
      disulfide bridge within each peptide. Some of the peptide:MBP fusions were also
      analyzed using surface plasmon resonance. Thus, our study shows the value of malE
      fusion vectors in characterizing phage-displayed peptides.

PMID- 9784194
TI  - Colorimetric determination of the purity of 3'-phospho adenosine 5'
      phosphosulfate and natural abundance of 3'-phospho adenosine 5'-phosphate at
      picomole quantities.
AB  - This work presents novel colorimetric methods not only to measure 3'-phospho
      adenosine 5'-phosphate (PAP) and 3'-phospho adenosine 5'-phosphosulfate (PAPS) in
      the range of picomoles, but also to determine the purity of PAPS or PAP
      contaminants in PAPS in the range of nanomoles. These methods exploit the
      availability of overexpressed phenol sulfotransferase (PST) and the fact that
      sulfuryl group transfer requires the use of PAP or PAPS as a cofactor or
      cosubstrate. Experimental results indicate that absorption at 400 nm due to the
      production of 4-nitrophenol (pNP) is catalyzed by PST when the sulfuryl group
      transfers from 4-nitrophenylsulfate (pNPS) to PAP or to 2-napthol. In the absence
      of an acceptor substrate, PAPS is hydrolyzed to PAP by PST and is determined by
      sulfation with pNPS before and after this reaction. The change of absorption of
      pNP at 400 nm corresponds to the amount of PAP that is hydrolyzed from PAPS.
      Moreover, a standard curve is constructed using authentic PAP and PAP-free PST.
      Furthermore, this curve is used to determine the amount of PAP in extracts of pig
      liver, rat liver, and Escherichia coli.

PMID- 9784195
TI  - Analysis of membrane phospholipid peroxidation by isocratic high-performance
      liquid chromatography with ultraviolet detection.
AB  - A new high-performance liquid chromatography (HPLC) for separation of
      phospholipid classes with ultraviolet (UV) detection at 210 nm was applied to
      study of peroxidation of the human erythrocyte membranes induced by soybean
      lipoxygenase. Phospholipid hydroperoxide production of each phospholipid was
      monitored at the same time by UV at 234 nm. Each phospholipid class was collected
      directly from the HPLC of phospholipids and was subjected to fatty acid analysis.
      All phospholipid classes except sphingomyelin were significantly decreased by
      lipoxygenase. Production of each phospholipid hydroperoxide was according to the
      decrease of its corresponding phospholipid class. Polyunsaturated fatty acids of
      each phospholipid were preferentially decreased with lipoxygenase, and degrees of
      the changes of the phospholipid classes corresponded to the amount of
      polyunsaturated fatty acids of each phospholipid. alpha-Tocopherol suppressed the
      decrease of the membrane phospholipids by peroxidation and suppressed also the
      production of malondialdehyde. However, production of phospholipid hydroperoxides
      appeared to be not suppressed by alpha-tocopherol. The present HPLC method proved
      to be sensitive to peroxidation of phospholipids and could detect the changes of
      each phospholipid class including phosphatidylserine and phosphatidylinositol at
      a single chromatographic elution. Production of hydroperoxide of each
      phospholipid could be detected simultaneously.

PMID- 9784196
TI  - An assay for glycogen synthase kinase 3 (GSK-3) for use in crude cell extracts.

PMID- 9784197
TI  - Elution of unmodified oligodeoxynucleotides from zinc-imidazole negatively
      stained polyacrylamide gels.

PMID- 9784198
TI  - Cytosines adjacent to methylated CpG sites can be partially resistant to
      conversion in genomic bisulfite sequencing leading to methylation artifacts.

PMID- 9784199
TI  - Is suckling behaviour a useful predictor of milk intake? A review.
AB  - In studies on mammalian parental investment, time spent suckling is often used as
      a predictor of the milk transferred from mother to infant. It is assumed that the
      rate of milk transfer is positively correlated with the time spent suckling.
      However, this assumption has not been tested and empirical studies show
      conflicting results. Nevertheless, in species in which suckling can readily be
      observed, time spent suckling is still used to measure milk transfer, although an
      increasing number of workers recognize that the measure is potentially
      inaccurate. A meta-analysis on studies that have correlated measures of time
      spent suckling with milk intake estimates based on weight gain revealed a weak
      positive relationship and significant heterogeneity between studies. Isotope
      labelling techniques for the measurement of milk transfer independent of
      behaviour have been in use since the 1970s, particularly in studies of species in
      which suckling is difficult to observe. Only one study has attempted to correlate
      behavioural measures with independent isotope measures, and it found no
      relationship between the two measures. I suggest that researchers have avoided
      such a test as it is unlikely that a strong relationship will be found between
      milk transfer and suckling behaviour, and I discuss the various factors that
      confound the relationship and contribute to high heterogeneity between studies.
      Consequently, the assumption that milk transfer can be measured by time spent
      suckling has inadequate empirical foundation, and needs to be tested using
      isotope-labelling methods. Copyright 1998 The Association for the Study of Animal
      Behaviour

PMID- 9784200
TI  - Small-male advantage in the territorial tropical butterfly Heliconius sara
      (Nymphalidae): a paradoxical strategy?
AB  - Large size is often decisive to victory in territorial disputes. Here we report
      for the first time a natural territorial advantage associated with small size,
      possibly exemplifying a 'paradoxical strategy' (Maynard Smith & Parker 1976,
      Animal Behaviour, 24, 159-175) in which small individuals with inferior resource
      holding power win war-of-attrition contests against superior adversaries because
      resource value/rate of cost accrual (V/K) is greater for small contestants. Males
      of the aposematic nymphalid butterfly Heliconius sara that defend scattered
      mating arenas in subtropical Brazilian forest have wings that are on average 3%
      shorter than males caught away from territories during any part of the year.
      Smaller residents tend to return to territories over longer periods, and field
      experiments show that intruders retreat faster when confronting smaller than
      average territory owners. Heliconius sara has a second, seemingly much more
      important mating system in which female pupae attract males pheromonally, and in
      which large males may be more successful in winning mates. Because it is unlikely
      that small H. sara have intrinsically superior resource holding power, and
      because territories should be about equally valuable to all males, we propose
      that large males, supposedly favoured in pupal mating, may risk losing more in
      terms of future reproductive success through chance injury in territorial fights
      (large K) and thus avoid combats with small opponents which risk little from
      injury because of their diminished mating prospects (small K). Copyright 1998 The
      Association for the Study of Animal Behaviour

PMID- 9784201
TI  - Do parental convict cichlids of different sizes value the same brood number
      equally?
AB  - We report a negative correlation between the weight of a female convict cichlid,
      Cichlasoma nigrofasciatum, and the magnitude of her defence against a model brood
      predator for a brood reduced to 100 eggs. We account for this relationship by the
      fact that a larger female is more likely to spawn a larger number of eggs than is
      a smaller female, making a fixed number of eggs relatively less valuable to the
      larger female. We performed two supplementary experiments that eliminated other
      logical explanations of the data. One experiment involved scaling the model brood
      predator. Results indicated that the size of model relative to the parent (over
      the range of ratios investigated) has no significant effect on magnitude of
      defence. The other experiment demonstrated no systematic trend in defence when
      brood number was unmanipulated. Thus, on average, larger females defended their
      naturally larger broods to the same extent as smaller females defended their
      smaller broods. Together, these three results suggest that female convict
      cichlids of different sizes do not value the same brood number equally. Copyright
      1998 The Association for the study of Animal Behaviour.

PMID- 9784202
TI  - Antipredator behaviour of hatchling snakes: effects of incubation temperature and
      simulated predators.
AB  - All animals that are exposed to predators must distinguish dangerous from
      nondangerous threats and respond correctly. In reptiles, emerging hatchlings are
      vulnerable to a wide range of predators, particularly if they emerge during
      daylight. In these experiments I tested the response of pine snake, Pituophis
      melanoleucus, hatchlings incubated at 22-23, 27-28, or 32-33 degreesC to visual
      and vibratory stimuli to examine antipredator behaviour. Emerging hatchlings were
      exposed to one of five conditions: (1) hawk model, (2) white head model with no
      facial features, (3) white head model with black eyes, (4) a person, or (5) a
      vibration without a visual stimulus. I tested the null hypotheses of no
      differences in response as a function of predator type or incubation temperature.
      Emergence behaviour when undisturbed was affected by incubating temperature, and
      antipredatory behaviour was affected by both predator type and incubation
      temperature. Pine snake hatchlings responded more protectively (withdrawal into
      tunnels) than defensively (striking), responded with less intensity to a
      vibration compared with visual predator stimuli, and required longer to respond
      to a head model without eyes than to all other predator types. Given the
      relatively small size of hatchlings, it is adaptive for them to withdraw into the
      nest rather than attack a predator. Hatchlings from eggs that were incubated at
      medium temperatures required less time to emerge from their underground nests
      when undisturbed, and had stronger protective responses than snakes incubated at
      other temperatures. These results suggest that hatchlings incubated at medium
      temperatures are generally less vulnerable to predators than hatchlings incubated
      at higher or lower temperatures. Copyright 1998 The Association for the Study of
      Animal Behaviour.

PMID- 9784203
TI  - Response to playback of nestling begging in the red-winged blackbird, Agelaius
      phoeniceus.
AB  - Nestling birds may honestly signal their need for food to provisioning adults, or
      begging might be a manipulative attempt to coerce additional food from providers,
      but in either case, providers respond to an increase in begging with an increase
      in feeding. We used playback of begging calls recorded from nestlings to
      determine whether male and female red-winged blackbirds increase their feeding
      rates in response to an apparent increase in begging. Both females and males fed
      broods at significantly higher rates after 5-min begging call playbacks than
      before, although only eight of 30 males were observed to feed nestlings in this
      study. In contrast, using the same playback design, neither females nor males
      altered their feeding rates significantly in response to broadcasts of noise.
      These results and others suggest that begging vocalizations are a basis for short
      term adjustments in the rate at which nestling birds are provisioned. These
      results are also compared with those of a similar study of the same species, in
      which playback had no significant effect on rates of provisioning. Copyright 1998
      The Association for the Study of Animal Behaviour.

PMID- 9784204
TI  - Red-winged blackbird females fail to increase feeding in response to begging call
      playbacks.
AB  - The begging behaviour of nestling birds appears to be the main signal telling
      parents how much food is needed by the brood. Not only may the accuracy of that
      information be reduced through exaggeration due to competition, but it may also
      vary with the age of the nestling. Younger nestlings may vary more in how
      frequently they call than older nestlings because they cannot discriminate
      stimuli as well. Thus, even if 'honest', begging from younger nestlings could be
      a less reliable hunger signal than that from older nestlings. We tested the
      prediction that parents should respond less to the increased frequency of begging
      from very young versus older nestlings by playing back begging calls at the nests
      of both younger (</=5 day) and older (>/=6 days) red-winged blackbirds, Agelaius
      phoeniceus. In neither case did parents respond with consistent increases in
      feeding, nor did young gain more weight during playbacks. This lack of response
      is discussed in relation to two other recent studies of blackbirds that did
      demonstrate increased feeding with playbacks of begging calls. Copyright 1998 The
      Association for the Study of Animal Behaviour.

PMID- 9784205
TI  - Benefits of begging for yellow-headed blackbird nestlings.
AB  - For begging to benefit chicks, parents must respond to increased begging by
      bringing more food. To investigate whether parents change their provisioning in
      response to begging levels, I enhanced the begging levels of broods of yellow
      headed blackbirds, Xanthocephalus xanthocephalus, using recorded vocalizations.
      In a short-term experiment, females and males doubled their visits to broods
      without reducing their load sizes during 2 h of playback. Nestlings gained more
      mass during the playback period than during a 2-h control period. In a long-term
      experiment, nestlings gained more mass in nests from which begging calls were
      broadcast over a 5-day period than nestlings in nests without playback. Copyright
      1998 The Association for the Study of Animal Behaviour.

PMID- 9784206
TI  - Perceptual mechanisms for individual vocal recognition in European starlings,
      Sturnus vulgaris.
AB  - The capacity for vocal recognition of individual conspecifics is well documented
      in many species, but the perceptual mechanisms that underlie this ability in
      oscines are less well understood. Using operant conditioning, we trained three
      groups of European starlings on a baseline task to discriminate the songs of one
      male starling from those of four others. Each subject heard songs from the same
      five singers, but the to-be-recognized individual varied among birds. We grouped
      the subjects according to sex and their degree of previous exposure to the songs
      used as stimuli in this experiment. The first group (N=5 males) identified their
      own songs from those of four familiar males. The second group (N=5 males) was
      familiar with the song stimuli, but none of the songs was their own. The third
      group (N=4 females) was unfamiliar with the songs. After learning the baseline
      discrimination, the subjects were exposed to new natural and synthetic stimuli.
      The subjects maintained the ability to identify correctly an individual on the
      basis of novel song bouts, and showed differential responding on the basis of the
      sequence of song types in song bouts that were modelled using Markov chains.
      Based upon patterns of responding to these different stimuli, we conclude that
      European starlings are capable of individual vocal recognition, and that this
      process is mediated by mechanisms involving the memorization of individually
      specific song types, the sequential ordering of song types within different bouts
      of an individual, and perhaps by individually specific spectral (or voice)
      characteristics that generalize across song types. Copyright 1998 The Association
      for the Study of Animal Behaviour.

PMID- 9784207
TI  - Paternal care enhances male reproductive success in pine engraver beetles.
AB  - Male pine engravers, Ips pini, assist their mates during reproduction by clearing
      debris from breeding galleries constructed beneath the bark of host trees. I
      measured duration of parental care provided by individual male pine engravers in
      the field, as well as the reproductive success of these males as indicated by the
      total number of eggs laid in their galleries and the mean distance between the
      eggs. Males remained in their galleries for 13-54 days (N=78, X+/-SE=33.0+/-0.9
      days). Male residence time was positively correlated with the mean distance
      between eggs in a gallery, as well as the total number of eggs laid in a gallery
      when the effect of male length was controlled statistically. Male-removal
      experiments corroborated these effects of male care on reproductive success, and
      showed that female mortality was higher in galleries from which the male had been
      removed than in controls. Duration of male care was inversely related to breeding
      density and male length. Despite remaining for less time in their galleries,
      larger males acquired the biggest harems. There was a positive correlation
      between the length of a male and the number of eggs laid per female, but this was
      not due to size-assortative mating. Because large male size is associated with a
      number of traits that are advantageous for securing mating opportunities, earlier
      departure from the gallery by larger males may be a consequence of those males
      having greater opportunities for future reproduction. Copyright 1998 The
      Association for the Study of Animal Behaviour.

PMID- 9784208
TI  - Condition-dependent timing of comb construction by honeybee colonies: how do
      workers know when to start building?
AB  - Colonies of honeybees, Apis mellifera, initiate new comb construction only when
      two conditions are met: (1) they are currently collecting nectar and (2) they
      have filled their available comb beyond a threshold level with brood and food. In
      this study I explored how the individual workers responsible for building might
      use readily accessible local cues to acquire this global information on colony
      and environmental state. In particular, I tested the hypothesis that comb is
      built by nectar receivers (bees specialized to receive nectar from foragers and
      store it in comb cells) that experience increased distension of their crops. Crop
      distension could serve as a cue that both conditions for building have been
      satisfied, because the bees' crops will fill up as they receive nectar from
      successful foragers and have difficulty finding comb in which to store it.
      However, two findings led to rejection of this hypothesis. First, very few nectar
      receivers participated in comb building. Most builders came from another,
      unidentified subpopulation of workers. Second, potential builders showed no
      increase in crop size correlated with the onset of new comb construction or with
      the development of conditions that favour comb building. This was true both for
      identified nectar receiver bees and for bees belonging to the age cohort at which
      wax secretion and comb building reach their peak levels. The behavioural
      repertoire of comb-building bees suggests that these builders come from a pool of
      underemployed bees that may evaluate colony state by direct inspection of comb
      cells. Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9784209
TI  - The influence of body coloration on shoaling preferences in fish.
AB  - Shoaling behaviour provides antipredator benefits that rely, to some extent, on a
      high degree of phenotypic homogeneity between individuals within the shoal.
      Therefore, fish should have the ability to discriminate between potential
      shoalmates, choosing to associate with individuals of similar appearance to
      themselves. We studied the effects of a single phenotypic character, body
      coloration, on association choices made by black and white mollies (Poecilia
      latipinna). When given a choice between a group of mollies of similar coloration
      and an empty compartment, individual test fish (black or white) spent
      significantly more time near the fish group. When given a choice between a group
      of black mollies and a group of white mollies, individual fish (black or white)
      spent significantly more time near the group of mollies of similar coloration to
      their own. When given a choice between a group of mollies of dissimilar
      coloration and an empty compartment, black and white mollies reacted differently.
      Black mollies spent significantly more time on the side of the central
      compartment closest to the white mollies, while there was no significant
      difference between the time spent by white mollies on either side of the test
      tank. Our results indicate that fish can use visual cues to discriminate actively
      between potential shoalmates on the basis of body coloration. Copyright 1998 The
      Association for the Study of Animal Behaviour.

PMID- 9784210
TI  - Influence of experimentally elevated testosterone on nest defence in dark-eyed
      juncos.
AB  - Testosterone affects the allocation of reproductive effort in male birds.
      Elevated testosterone causes male dark-eyed juncos, Junco hyemalis, to decrease
      care of dependant offspring, but this generalization is based largely on reduced
      provisioning rates by males treated with testosterone. Therefore, we used a
      predator model to explore the relationship between testosterone and nest defence,
      a more immediate measure of male parental effort. Control males (C-males) were
      more likely to respond within 10 min to a mount of an eastern chipmunk, Tamias
      striatus, placed at the nest than were testosterone-treated males (T-males).
      However, among males that did respond within 10 min, T-males initiated nest
      defence as fast as C-males and defended the nest with equal intensity. Females
      initiated nest defence more rapidly and struck the mount more often than their
      mates, regardless of the male's treatment. Overall, the decreased likelihood of T
      males being present for nest defence (perhaps mediated by their large home
      ranges) may increase predation rates at their nests and represent an important
      cost of elevated testosterone levels. Copyright 1998 The Association for the
      Study of Animal Behaviour

PMID- 9784211
TI  - Local variation in Barbary macaque shrill barks.
AB  - We examined vocalizations of Barbary macaques, Macaca sylvanus, given in response
      to a dog, in two populations, at Rocamadour, France, and Salem, Germany. Calls
      were recorded from 16 individuals in Rocamadour and 23 individuals in Salem.
      Despite an overall similarity, an acoustic analysis revealed significant
      differences in the call structure between populations. To test the perceptual
      salience of these acoustic differences, we conducted playback experiments in both
      populations in which calls from the own or the other population were broadcast.
      The overall response pattern did not differ significantly between the populations
      with regard to the origin of the call. However, subjects responded slightly, but
      significantly longer after playback of calls from the other group. Although call
      function apparently determined the general response of subjects, they none the
      less discriminated between calls from different origins. These results suggest a
      small but possibly meaningful plasticity in call production. Copyright 1998 The
      Association for the Study of Animal Behaviour.

PMID- 9784212
TI  - Parental recycling of nestling faeces in the common swift.
AB  - Several hypotheses have been proposed to explain why parent birds eat their
      nestlings' faecal sacs. Among them, the parental nutrition hypothesis suggests
      that faeces may provide alternative food to parent birds, while the economic
      disposal hypothesis proposes that eating faeces represents an economical
      alternative to carrying them away when birds are engaged in parental activities.
      In both cases the elimination of faeces could prevent contamination of the nest
      (nest sanitation). In the present study, we tested these hypotheses on the common
      swift, Apus apus. The behaviour of parents at the nest was videotaped and
      analysed in relation to sex, brood size and nestling age. The parents regularly
      swallowed faecal sacs during the first 3 weeks after the nestlings hatched, but
      only occasionally thereafter until they fledged. Both sexes ingested sacs at a
      similar rate in the first week after hatching, and ingestion rate was directly
      related to the number of feeding visits. Females ate significantly more sacs than
      males overall. The parents consumed faeces after actively searching into and
      around the nest cup, also during brooding spells. However, brooding decreased
      with increasing brood size and nestling age, while faeces consumption increased.
      Our results are consistent with the hypothesis that parent birds ingest their
      nestling faeces to recycle water and nutrients, making the 'best of a bad job'
      during periods of high energetic requirements. In addition, ingestion of faeces
      may be an alternative strategy to delay hunger and to facilitate the allocation
      of food to the offspring. As the nestlings grew, parents ate fewer faecal sacs.
      The increased begging behaviour of the young appeared to be an important factor
      in determining the decline of faeces consumption, as it hindered parents
      approaching the nest. Copyright 1998 The Association for the Study of Animal
      Behaviour.

PMID- 9784213
TI  - Interference competition and the functional response of oystercatchers searching
      for cockles by touch.
AB  - We examined interference competition for food in oystercatchers, Haematopus
      ostralegus L., feeding on cockles, Cerastoderma edule L., when kleptoparasitism
      was infrequent. These birds opened cockles by hammering a hole in the shell,
      searched for them by touch and experienced densities of feeding conspecifics that
      ranged from 0 to 2362.5 birds/ha. Handling times were not significantly
      correlated with competitor density, but the probability of successfully opening a
      cockle declined significantly as competitor density increased because birds were
      more likely to abandon cockles they had found. Birds were also significantly more
      likely to carry cockles away from where they were found prior to attempting to
      open them as competitor density increased. We used an optimal diet model to
      predict maximum energy intake rates achievable for birds feeding on a given prey
      population, and experiencing a range of competitor densities. Despite affecting
      foraging behaviour, the model showed that competitor density had a negligible
      impact on overall intake rates. Although kleptoparasitism was rare in our study
      population, only 1.5% (9/586) of cockles being lost to parasites, a recent model
      suggests that it was likely to be profitable, under the conditions experienced by
      our birds. We suggest that kleptoparasitism might be infrequent because birds
      could reduce its likelihood by adjusting their behaviour, with only a minimal
      cost in terms of a reduced intake rate. Behaviour-based models of interference
      competition, therefore, need to consider a range of potentially complex avoidance
      behaviours when attempting to describe the dynamics of this process. Copyright
      1998 The Association for the Study of Animal Behaviour

PMID- 9784214
TI  - Gradually escalating fights and displays: the cumulative assessment model.
AB  - I present a 'cumulative assessment model', which describes dyadic antagonistic
      encounters in which a contestant's decision whether to persist or to flee is
      based upon a cumulative sum of its adversary's actions. It is particularly
      relevant to ritualized fights in which only a certain total of direct physical
      damage can be tolerated, but it can also be applied to displays without physical
      contact provided they are subject to external time costs (such as from predation
      risk). The cumulative assessment model provides an alternative to the sequential
      assessment model or the war of attrition as a description of temporally extended
      displays. I describe how the three may be distinguishable in real situations by
      consideration of escalatory properties and of characteristic intrapopulation
      variation. The model predicts that, under some circumstances, losers may start
      the encounter at a lower level of intensity but increase that level more rapidly
      than winners. Such behaviour has been observed in the cyprinodont fish
      Aphyosemion striatum. Copyright 1998 The Association for the Study of Animal
      Behaviour.

PMID- 9784215
TI  - Active brood care in an amphipod: influences of embryonic development,
      temperature and oxygen.
AB  - Female amphipods (Crustacea) carry their fertilized eggs in an external brood
      pouch until the fully formed juveniles emerge (passive brood care). They may also
      direct specific maternal activities towards the brood (active brood care). We
      show that Crangonyx pseudogracilis, which typically populates fresh-waters
      subject to wide fluctuations in temperature and dissolved oxygen, engages in a
      highly responsive form of active brood care. This involves a flexing motion by
      the female that expands the brood pouch and increases the suspension of the eggs
      in the surrounding medium, accompanied by ventilation of the brood pouch and the
      'cycling' of eggs therein. Females also selectively eject nonviable eggs from
      their broods. We investigated the expression of this brood care behaviour in
      relation to intrinsic and extrinsic factors relevant to the development of
      broods. The time spent by females in this behaviour initially increased as
      embryos developed, but decreased once advanced embryos began to self-ventilate
      and to have a heart pulse. In addition, both increased temperature and decreased
      oxygen concentration resulted in increased levels of brooding behaviour. We thus
      propose that this behaviour functions to ameliorate the microclimate of the brood
      pouch and serves the changing metabolic demand of the brood, as influenced by the
      interaction of embryonic development with temperature/dissolved oxygen regime. In
      addition, this behaviour may be a key adaptation facilitating the success of this
      North American species as an invader of disturbed and polluted freshwaters in
      Europe and elsewhere. Evidence is emerging that other amphipods associated with
      harsh environmental conditions also show such active maternal brood care.
      Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9784216
TI  - The identity of the previous visitor influences flower rejection by nectar
      collecting bees.
AB  - In the field, recently probed flowers of borage, Borago officinalis, typically
      contained little or no nectar (and hence were relatively unrewarding), whether
      probed by a bumblebee, Bombus spp., worker or a honeybee, Apis mellifera.
      However, a nectar-collecting bee was likely to reject a recently probed flower
      only if the previous visitor was a conspecific (honeybees) or congener
      (bumblebees); the effect was especially marked in honeybees. Honeybees rejected
      more than 80% of flowers probed by conspecifics less than 20 s previously, but
      less than 20% of flowers probed by bumblebees less than 20 s previously. Only if
      the previous bee was a conspecific or congener did the probability of a bee
      probing a flower increase with the time since the last probing visit. Otherwise,
      the probability of a bee probing was independent of the time elapsed since the
      last visit. Bees' reactions to flowers whose nectar content had been manipulated
      independently of prior visits suggested that bees were repelled from flowers by
      species- or genus-specific chemical cues deposited by previous bees. Laboratory
      studies elsewhere have reported that honeybees are repelled from artificial
      feeders by volatile bee-deposited chemicals. My results constitute strong
      evidence that such cues are used by nectar-collecting honeybees in the field, and
      also suggest that bumblebees respond to similar cues. Calculations show that the
      ability to detect recently visited flowers may help bees to make a foraging
      profit, especially when bee densities are high. Thus, bee-deposited chemicals may
      confer information and economic advantages to foraging alongside conspecifics or
      congeners. Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9784217
TI  - The influence of genes for melanism on the activity of the flour moth, Ephestia
      kuehniella.
AB  - We investigated the effects of genes controlling melanism on levels and patterns
      of activity, potential nonvisual components of fitness, of adult Mediterranean
      flour moths, Ephestia kuehniella Zeller (1879). Six genotypes of two melanic
      strains (Ala nigra and black) were used. We monitored continuously the walking or
      flight activity of 45 mated females per genotype during the third night of their
      lives, using automatic electrostatic techniques to carry out the measurements.
      Although there was high individual variation within genotypes, bb (melanic)
      females were more active than the two nonmelanic genotypes of the black strain
      (b+, ++) because they tended to show more bouts of activity. There were no
      differences in the average length of these bouts, or in the timing of initial and
      final activity. Overall, the females of the black strain were significantly more
      active than the females of the Ala nigra strain. The results are discussed in the
      context of the evolution of melanism in moths. Copyright 1998 The Association for
      the Study of Animal Behaviour

PMID- 9784218
TI  - Sex and schooling behaviour in the Trinidadian guppy.
AB  - We tested the hypothesis that sexual asymmetry in mating costs affects choice of
      schooling partner in fish. Female guppies, Poecilia reticulata, from the
      Tacarigua River, Trinidad, associated preferentially with other (familiar)
      females from their natural wild school, while males did not show such a
      preference. This implies that wild guppy schools are not random assemblages of
      conspecifics. Females form the core of natural schools while males seem to trade
      off the potential advantages of schooling with familiar conspecifics against
      increased mobility in search of mating opportunities. We discuss the implications
      of these findings in relation to cooperative behaviour, gene flow and population
      differentiation. Copyright 1998 The Association for the Study of Animal Behaviour

PMID- 9784219
TI  - Effects of social organization, age and aggressive behaviour on allosuckling in
      wild fallow deer.
AB  - I investigated the occurrence, frequency and distribution of allosuckling in a
      wild population of fallow deer, Dama dama, throughout the lactation period during
      1992 in southern Sweden. A total of 292 suckling bouts were observed in four
      groups; in 43% of these, fawns were seen sucking from a female that was not the
      mother. Allosuckling occurred in a higher percentage of suckling bouts as the
      lactation period progressed and all 16 fawns participated to various degrees. Of
      the 16 females, 13 suckled nonoffspring fawns but their behaviour towards these
      fawns varied greatly. Allosuckling was positively correlated with the age of the
      females and negatively correlated with the rate of their aggressive behaviour.
      Since allosuckling was not performed between groups but was common between
      related members in a stable social unit and was expressed reciprocally between
      the oldest individuals in the group, allosuckling could be a result of kin
      selection and/or reciprocal altruism. Copyright 1998 The Association for the
      Study of Animal Behaviour.

PMID- 9784220
TI  - Nestling mouth colour: ecological correlates of a begging signal.
AB  - The mouths of begging nestlings vary widely in colour, ranging from yellow in
      robins, Erithacus rubecula, to red in reed buntings, Emberiza schoeniclus. Two
      functions have been suggested for bright nestling mouth colour: (1) it may
      improve the detectability of chicks, particularly in poorly lit nests and (2)
      within species, it may signal need. We tested these hypotheses in a comparative
      analysis, measuring the mouth colours of nestlings from 31 species under
      conditions of standardized light availability and food deprivation. Changes in
      mouth colour signalled need only among the seed-regurgitating finches. In these
      species there was a 'red flush' at the onset of begging, which became redder with
      increasing food deprivation. No other species showed these changes, including the
      closely related chaffinch, Fringilla coelebs, which feeds its young insects. We
      found no evidence that mouth colour was correlated with the light available in
      the nest. We did find, however, that nestlings in darker nests improved their
      conspicuousness through the relative colour and size of the flange that borders
      their brightly coloured mouths. Nestlings from darker nests had relatively wider
      flanges, which were whiter and less densely coloured in relation to their mouth
      colour, than those of chicks reared in better illuminated nests. Clutch size was
      not related to mouth or flange colour, or relative flange size. We suggest that
      nestling mouth colour has not been selected to make chicks detectable, but that
      this is the function of the surrounding flange. We also discuss reasons why
      signals of need through mouth colour are not more widespread. Copyright 1998 The
      Association for the Study of Animal Behaviour.

PMID- 9784221
TI  - Female preference for fly song: playback experiments confirm the targets of
      sexual selection.
AB  - The courtship song of Drosophila is thought to be involved in sexual selection
      and species recognition. Because of the mating system of flies, however, directly
      demonstrating that song influences female preference is difficult. The majority
      of previous studies have used an experimental design that potentially confounds
      male and female reactions to song. In D. montana, correlational evidence has
      suggested that males that produce short sound pulses consisting of a high number
      of sound cycles (i.e. a high carrier frequency) have a higher mating success than
      other males. In this study, we played synthetic song that varied in pulse length
      and carrier frequency to individual females in the laboratory, both alone and in
      the presence of mute males. We scored female preference via an acceptance
      posture, 'wing spreading', which the females of this species usually display
      prior to mounting by a male. Females responded to synthetic song in the absence
      of males. The presence of mute males significantly increased their overall
      responsiveness, but the relative effectiveness of the songs did not change,
      eliminating male reaction to song as a possible confounding factor in the
      results. The interaction between pulse length and carrier frequency determined
      the discrimination between song types, with females responding most readily to
      song consisting of short pulses with a high carrier frequency. Thus, direct
      examination of female preferences supports the previous studies of male mating
      success, and confirms female song preference as a likely determinant of male
      mating success. Copyright 1998 The Association for the Study of Animal Behaviour

PMID- 9784222
TI  - A method for testing association patterns of social animals.
AB  - Association indices were originally developed to describe species co-occurrences,
      but have been used increasingly to measure associations between individuals.
      However, no statistical method has been published that allows one to test the
      extent to which the observed association index values differ from those of a
      randomly associating population. Here, we describe an adaptation of a test
      developed by Manly (1995, Ecology, 76, 1109-1115), which uses the observed
      association data as a basis for a computer-generated randomization. The observed
      pattern of association is tested against a randomly created one while retaining
      important features of the original data, for example group size and sighting
      frequency. We applied this new method to test four data sets of associations from
      two populations of Hector's dolphin, Cephalorhynchus hectori, using the Half
      Weight Index (HWI) as an example of a measure of association. The test
      demonstrated that populations with similar median HWI values showed clear
      differences in association patterns, that is, some were associating nonrandomly
      whereas others were not. These results highlight the benefits of using this new
      testing method in order to validate the analysis of association indices.
      Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9784223
TI  - Scent marks as reliable signals of the competitive ability of mates.
AB  - The quality of an individual's odour can allow potential mates to discriminate
      against individuals of low social class, poor health status or unsuitable
      genotype. Competitive scent marking provides a further mechanism which could
      allow mates to discriminate between individuals of apparently high quality. The
      presence or absence of fresh countermarks from competitors within an owner's
      territory or area marked by a dominant animal provides a reliable indicator of
      the owner's ability to defend its territory or dominate competitors. This could
      be used by potential mates to discriminate between individuals advertising their
      apparently high competitive ability through their scent-marking behaviour and
      odour quality. We tested this by manipulating scent marks in the neighbouring
      territories of wild-caught male house mice, Mus domesticus. As predicted,
      oestrous females used scent marks to select males apparently able to defend
      exclusive territories over those unable to exclude intruders. Females were more
      strongly attracted to the odour of owners of exclusively marked territories and
      showed more sexually related behaviour when interacting with these males.
      Furthermore, while females preferred a territory containing a better protected
      nest site regardless of the owner's apparent competitive ability, they still used
      the presence or absence of intruder countermarks when selecting a potential mate.
      This suggests that females use scent marks as a reliable signal of the best
      quality mate among neighbouring males independently of their nest location. Since
      assessment depends on both the territory holder's own marks and those of
      competitor males, countermarking is likely to be an important mechanism of
      competition for mates between neighbours. Copyright 1998 The Association for the
      Study of Animal Behaviour

PMID- 9784224
TI  - Inbreeding and divorce in blue and great tits.
AB  - In blue tits, Parus caeruleus, and other wild birds, matings between close
      relatives or between genetically similar individuals are associated with fitness
      costs, often in terms of lower hatching success of the eggs. If individuals
      cannot assess their genetic similarity to potential mates, those fitness costs
      may be hard to avoid; however, they may use the proportion of unhatched eggs in
      their clutch as a cue for their mate choice in the next season. We tested this
      hypothesis using data from a long-term population study on blue and great tits,
      Parus major. Divorce in response to inbreeding depression can be considered a
      special case of the 'incompatibility hypothesis'. As predicted from this
      hypothesis, both male and female blue tits benefited from divorce when part of
      their clutch failed to hatch. There was no evidence however, that divorce in blue
      or great tits was related to the presence of unhatched eggs in the nest.
      Copyright 1998 The Association for the Study of Animal Behaviour

PMID- 9784225
TI  - Light-induced migration behaviour of Daphnia modified by food and predator
      kairomones.
AB  - Lake-dwelling waterfleas, Daphnia, often face a dilemma. Food availability is
      highest, near the water surface, but predation by visually hunting predators is
      also most severe. Swimming downward at dawn reduces predation risk, but food
      availability and temperature also decrease with depth. We tested whether Daphnia
      process information derived from food and predator presence to estimate the costs
      and benefits of migration, and to determine when it pays to swim down. We studied
      downward swimming of D. galeataxhyalina in response to stepwise accelerations of
      relative increases in the intensity of light at several food and fish kairomone
      concentrations. Both had a modifying, additive, although independent effect. We
      studied in six clones the clonal differences of this environmentally induced
      plasticity of photobehaviour. These clones were caught at two depths at noon
      during a period of vertical migration in Lake Maarsseveen (the Netherlands), and
      so presumably differed in vertical migration behaviour. Two clones, one from the
      epilimnion and one from the hypolimnion, showed a particularly significant
      difference in migration behaviour. Copyright 1998 The Association for the Study
      of Animal Behaviour.

PMID- 9784227
TI  - Individual mating success, lek stability, and the neglected limitations of
      statistical power.
AB  - The evolution of leks (aggregations of males displaying to females) cannot be
      explained solely by an increasing average gain in matings for each male as group
      size increases. This is because the mating skew, that is, the inequality among
      males in mating success, is often high and may vary with lek size. Here, we show
      that the common observation that matings become more evenly divided as lek size
      increases is also insufficient to explain by itself the benefits of aggregating.
      The benefits to individual males are highly sensitive to the exact relationship
      between mating skew and lek size, and very similar relationships can lead to
      opposite predictions concerning individual benefits. With data on published
      mating success for 18 species (71 leks), we show that different species have very
      similar skew versus lek size relationships. With current sample sizes, however,
      there is insufficient statistical power to distinguish between completely
      different alternatives concerning individual optima of males. Copyright 1998 The
      Association for the Study of Animal Behaviour

PMID- 9784226
TI  - Discrete conventional signalling of a continuous variable.
AB  - In aggressive interactions, animals often use a discrete set of signals, while
      the properties being signalled are likely to be continuous, for example fighting
      ability or value of victory. Here we investigate a particular model of fighting
      that allows for conventional signalling of subjective resource value to occur.
      Perfect signalling and no signalling are not evolutionarily stable strategies
      (ESSs) in the model. Instead, we find ESSs in which partial information is
      communicated, with discrete displays signalling a range of values rather than a
      precise one. The result also indicates that communication should be more precise
      in conflicts over small resources. Signalling strategies can exist in fighting
      because of the common interest in avoiding injuries, but communication is likely
      to be limited because of the fundamental conflict over the resource. Our results
      reflect a compromise between these two factors. Data allowing for a thorough test
      of the model are lacking; however, existing data seem consistent with the
      obtained theoretical results. Copyright 1998 The Association for the Study of
      Animal Behaviour.

PMID- 9784228
TI  - Auditory sensitivity in the great tit: perception of signals in the presence and
      absence of noise.
AB  - Absolute and masked auditory thresholds (critical masking ratios) were determined
      behaviourally in the great tit, Parus major, using a GO/NOGO-procedure. Absolute
      sensitivity was measured between 0.25 and 10 kHz. In the absence of noise, great
      tits were most sensitive to frequencies between 2 and 4 kHz. In background noise,
      however, the sensitivity was only a function of the noise level and was
      independent of frequency. Critical masking ratios determined for signals between
      0.25 and 8 kHz were almost constant (median values varied between 23.8 and 25.9
      dB) irrespective of signal frequency. Therefore, in contrast to the majority of
      bird species, great tits have unusually low critical masking ratios at high
      frequencies. This means that great tits can use high-frequency vocalizations to
      communicate efficiently in noisy (i.e. natural) environments. Copyright 1998 The
      Association for the Study of Animal Behaviour.

PMID- 9784229
TI  - Watch and learn: preview of the fighting ability of opponents alters contest
      behaviour in rainbow trout.
AB  - The costs associated with initial conflicts could be reduced if animals can
      assess the fighting ability of possible future opponents by watching their
      contest success against other individuals. We tested this hypothesis by
      conducting repeated dyadic dominance trials on size-matched juvenile rainbow
      trout, Oncorhynchus mykiss. In the first trial a dyadic contest was 'observed' by
      a single fish separated by a transparent divider. In the second trial, the
      observer was paired against either the 'familiar' dominant fish or an unfamiliar
      dominant fish from the first trial. We predicted that observers should settle
      conflicts with previewed opponents faster and with less aggression than those
      with unfamiliar fish. This prediction was supported for observers that lost
      against a previewed competitor, since these fish reduced their aggression more
      rapidly than did unfamiliar observers. Familiar observers that won, however,
      showed a more rapid increase in aggression compared with unfamiliar winning
      observers. This suggests that, regardless of whether an observer challenges the
      initial dominant, this 'decision' is taken more rapidly in conflicts with
      preassessed contestants, because of the a priori information about their fighting
      ability. Since preassessment could save energy and allow effort to be
      concentrated on contests with a high payoff/probability of winning, selection may
      favour preview strategies when contest competition over resources is important
      for fitness. Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9784230
TI  - Sperm trading by volume in a hermaphroditic flatworm with mutual penis
      intromission.
AB  - When sperm donation is costly, insemination is reciprocal and ejaculate size is a
      good predictor of an individual's reproductive state, internally fertilizing
      hermaphrodites are expected to donate more sperm when they receive more,
      resulting in sperm trading by volume. We compared the amounts of sperm exchanged
      reciprocally between partners of the planarian flatworm Dugesia gonocephala. In
      the field, mating individuals had more self sperm, but were less allosperm
      depleted than nonmating individuals. Larger individuals also had more self sperm
      and transferred more sperm. Although individuals mated assortatively by size,
      self sperm reserves were not correlated within pairs. Nevertheless, mating
      partners exchanged similar amounts of sperm, even after correcting for self sperm
      availability. Hence, individuals give more sperm not only when they have more,
      but also when they receive more. This is the first indication that sperm trading
      by volume occurs in a simultaneous hermaphrodite with mutual penis intromission.
      It appears to be achieved by both partners donating sperm until the partner with
      the lowest self sperm reserves finishes ejaculation and completes spermatophore
      transfer. In response, the other partner ends sperm donation as well, and
      transfers its spermatophore with only a short delay. The evolution of conditional
      sperm exchange in this species may be explained by the fact that male mating rate
      is limited owing to the time needed to replenish self sperm reserves. Copyright
      1998 The Association for the Study of Animal Behaviour

PMID- 9784231
TI  - Logistic analysis of animal contests.

PMID- 9784232
TI  - Two missense point mutations in different alleles in the 3-hydroxy-3
      methylglutaryl coenzyme A lyase gene produce 3-hydroxy-3-methylglutaric aciduria
      in a French patient.
AB  - Two novel point mutations in the 3-hydroxy-3-methylglutaryl coenzyme A lyase gene
      were found in a French patient with double heterozygous 3-hydroxy-3
      methylglutaric aciduria. Amplification by reverse transcriptase-polymerase chain
      reaction of the mRNA using five different pairs of oligonucleotides produced no
      differences in the fragments amplified with respect to the control. Single-strand
      conformation polymorphism analysis showed that only one amplified fragment was
      different in the patient vs. control. Sequencing of the amplified fragments
      showed two missense point mutations, A698G and T788C, each of them mixed with the
      wild-type sequence. These mutations produced the changes H233R and L263P, leading
      to changes in the enzyme activity, which was largely abolished. The father and
      one brother of the proband were heterozygous for the L263P mutation and the
      mother and one daughter were heterozygous for the H233R mutation, which confirms
      the double-heterozygous character of the patient. Another sibling was free of the
      mutations. An enzymatic restriction analysis has been proposed to screen the
      occurrence of these two mutations in future patients.

PMID- 9784233
TI  - Investigation of a catalytic zinc binding site in Escherichia coli L-threonine
      dehydrogenase by site-directed mutagenesis of cysteine-38.
AB  - L-Threonine dehydrogenase catalyzes the NAD+-dependent oxidation of threonine
      forming 2-amino-3-ketobutyrate. Chemical modification of Cys-38 of Escherichia
      coli threonine dehydrogenase, whose residue aligns with the catalytic zinc
      binding residue, Cys-46, of related alcohol/polyol dehydrogenases, inactivates
      the enzyme [B. R. Epperly and E. E. Dekker (1991) J. Biol. Chem. 266, 6086-6092;
      A. R. Johnson and E. E. Dekker (1996) Protein Sci., 382-390]. To probe its
      function, Cys-38 was changed to Ser, Asp, and Glu by site-directed mutagenesis.
      Mutants C38S and C38D were purified to homogeneity and found to be, like the wild
      type enzyme, homotetrameric proteins containing one Zn2+ atom per subunit. The
      circular dichroism spectra of these mutants were essentially identical to that of
      the wild-type enzyme. Mutant C38S was catalytically inactive but mutant C38D had
      a specific activity of 0.2 unit/mg, a level approximately 1% that of the wild
      type enzyme. After it was incubated with 1 mM Zn2+ and then assayed in the
      presence of 15 mM Zn2+, mutant C38S showed only a trace of enzymatic activity
      (i.e., 0.013 unit/mg). Preincubation of mutant C38D with 5 mM Zn2+, Co2+, or Cd2+
      increased its activity 57-, 6-, or 3-fold, respectively; 1 mM Mn2+ halved and 0.5
      mM Hg2+ abolished activity. Zn2+-stimulated mutant C38D showed these properties:
      apparent substrate activation at low threonine concentrations, a maximum activity
      of 27 units/mg with 20 mM threonine, and inhibition by high levels of substrate;
      an activation Kd = 3 mM Zn2+; and a pH optimum of 8.4 (in contrast to pH 10.3 for
      the wild-type enzyme). Without added Zn2+, mutant C38D is equally active with
      threonine and 2-amino-3-hydroxypentanoate, but Zn2+-activated mutant C38D is 10
      fold more reactive with threonine than with 2-amino-3-hydroxypentanoate. In the
      absence of added metal ions, wild-type enzyme similarly uses substrates other
      than threonine and shows a dramatic increase in activity with only threonine when
      stimulated by either Cd2+ or Mn2+; added Zn2+ has no effect on activity with
      threonine. Cys-38 of threonine dehydrogenase, therefore, is located in an
      activating divalent metal ion-binding site. Having a negatively charged residue
      like Asp in this position allows the binding of a catalytic Zn2+ ion which
      enhances activity with threonine and reduces activity with substrate analogs.
      Whether Cys-38 of wild-type threonine dehydrogenase binds a catalytic metal ion
      (possibly Zn2+) in vivo remains to be established.

PMID- 9784235
TI  - Cellular responses to nitric oxide: role of protein S-thiolation/dethiolation.
AB  - Nitrosothiols, the product of the reaction of nitric oxide-derived species (NOx)
      with thiols, participate in both cell signaling and cytotoxic events. Glutathione
      has recently been shown to modulate nitrosothiol-mediated signal transduction and
      to protect against NOx-mediated cytotoxicity. We have investigated the role of
      protein S-thiolation/dethiolation as a potential mechanism by which glutathione
      regulates nitrosothiol signaling and toxicity. Our data show that exogenous
      sources of NOx decreased both free protein thiol and total glutathione levels in
      endothelial cells. The decrease in glutathione levels could not be accounted for
      by formation of S-nitrosoglutathione (GSNO) since borohydride treatment of the
      nonprotein fraction of cell extracts did not restore glutathione levels, whereas
      borohydride treatment of protein-containing cell extracts led to recovery of
      glutathione levels. The NOx-mediated decrease in glutathione and protein thiol
      content was correlated with an increase in protein mixed disulfide formation, as
      measured by the incorporation of [35S]glutathione into cellular proteins.
      [35S]glutathione was incorporated into proteins via a covalent disulfide bond
      since dithiothreitol removed the radiolabel from cellular proteins. The
      withdrawal of the exogenous NOx source led to recovery of free protein thiol and
      cellular glutathione levels, which correlated with the dethiolation of proteins.
      Dethiolation required the action of the glutathione redox system since 1, 3-bis(2
      chloroethyl)-1-nitrosourea, an inhibitor of glutathione reductase, blocked both
      the recovery of glutathione levels and the dethiolation of proteins. These
      results suggest that exposure of cells to NOx does not lead to accumulation of
      GSNO but rather stimulates protein S-thiolation, a mechanism which may have
      important implications with respect to nitrosothiol signaling and toxicity.

PMID- 9784234
TI  - A highly active protein repair enzyme from an extreme thermophile: the L
      isoaspartyl methyltransferase from Thermotoga maritima.
AB  - We show that the open reading frame in the Thermotoga maritima genome tentatively
      identified as the pcm gene (R. V. Swanson et al., J. Bacteriol. 178, 484-489,
      1996) does indeed encode a protein L-isoaspartate (D-aspartate) O
      methyltransferase (EC 2.1.1.77) and that this protein repair enzyme displays
      several novel features. We expressed the 317 amino acid pcm gene product of this
      thermophilic bacterium in Escherichia coli as a fusion protein with an N-terminal
      20 residue hexa-histidine-containing sequence. This protein contains a C-terminal
      domain of approximately 100 residues not previously seen in this enzyme from
      various prokaryotic or eukaryotic species and which does not have sequence
      similarity to any other entry in the GenBank databases. The C-terminal region
      appears to be required for enzymatic function as no activity is detected in two
      recombinant constructs lacking this domain. Sedimentation equilibrium analysis
      indicated that the enzyme is monomeric in solution. The Km values for measured
      for peptide and protein substrates were found to be intermediate between those of
      the high-affinity human enzyme and those of the lower-affinity wheat, nematode,
      and E. coli enzymes. The enzyme was extremely heat stable, with no loss of
      activity after 60 min at 100 degreesC. Enzyme activity was observed at
      temperatures as high as 93 degreesC with an optimal activity of 164 nmol/min/mg
      protein at 85 degreesC. This activity is approximately 18-fold higher than the
      maximal activities of mesophilic homologs at 37 degreesC. These data suggest that
      the Thermotoga enzyme has unique features for initiating repair in damaged
      proteins containing L-isoaspartyl residues at elevated temperatures.

PMID- 9784236
TI  - Purification of and kinetic studies on a cloned protoporphyrinogen oxidase from
      the aerobic bacterium Bacillus subtilis.
AB  - The previously cloned and expressed protoporphyrinogen oxidase from Bacillus
      subtilis has been purified to homogeneity by Ni2+ affinity chromatography using a
      His6 tag and characterized. The enzyme has a molecular weight of approximately
      56,000 daltons, a pI of 7.5, a pH optimum (protoporphyrinogen) of 8.7, and a
      noncovalently bound flavine adenine dinucleotide cofactor. The Michaelis
      constants (Km) for protoporphyrinogen-IX, coproporphyrinogen-III, and
      mesoporphyrinogen-IX are 1.0, 5.29, and 4.92 microM, respectively. Polyclonal
      antibody to B. subtilis protoporphyrinogen oxidase demonstrated weak cross
      reactivity with both human and Myxococcus xanthus protoporphyrinogen oxidase. B.
      subtilis protoporphyrinogen oxidase is not inhibited by the diphenyl ether
      herbicide acifluorfen at 100 microM and is weakly inhibited by methylacifluorfen
      at the same concentration. Bilirubin, biliverdin, and hemin are all competitive
      inhibitors of this enzyme.

PMID- 9784237
TI  - Effects of photodynamic action on respiration in nonphosphorylating mitochondria.
AB  - We have studied the effects of singlet oxygen produced by photodynamic action on
      respiration in nonphosphorylating mitochondria (state 4). Isolated rat liver
      mitochondria were incubated with 3 microM hematoporphyrin and irradiated at 365
      nm with a fluence rate of 25 W/m2. After short durations of irradiation, state 4
      respiration with beta-hydroxybutyrate as substrate increases while respiration
      with succinate is negligibly affected. When mitochondria have been uncoupled with
      carbonylcyanide-p-trifluoromethoxyphenyl hydrazone before irradiation, no change
      occurs in beta-hydroxybutyrate-driven respiration, while succinate-driven
      respiration strongly decreases. Stimulation of state 4 NADH respiration cannot be
      explained by slippage of the NADH ubiquinone oxidoreductase because the
      stoichiometry of the redox pump was found insensitive to photodynamic action. In
      the light of the metabolite theory for linear enzymatic chains applied to state 4
      respiration (Brand et al., Biochem. J. 255, 535-539, 1988), these results suggest
      that stimulation of NADH respiration is simply due to an increase of membrane
      leaks which occurs after irradiation. In the case of succinate-driven
      respiration, a strong inhibition of succinate dehydrogenase activity has been
      demonstrated after irradiation. It can be suggested that this inhibition
      introduces a negative control coefficient over state 4 respiration,
      counterbalancing the effects due to leakage.

PMID- 9784238
TI  - Phenytoin alters transcript levels of hormone-sensitive lipase in muscle from
      horses with hyperkalemic periodic paralysis.
AB  - In equine hyperkalemic periodic paralysis (HyperPP), there is evidence suggesting
      that the primary defect in the sodium channel is associated with a secondary
      alteration in triacylglycerol-associated fatty acid metabolism (TAFAM) in
      skeletal muscle. Furthermore, TAFAM may be involved in the therapeutic action of
      phenytoin. The effects of phenytoin treatment on the transcript levels of three
      key proteins in TAFAM, hormone sensitive lipase (HSL), carnitine
      palmitoyltransferase (CPT), and fatty acid binding protein (FABP), were examined.
      These transcripts were quantitated by competitive reverse transcription
      polymerase chain reaction in undifferentiated and differentiated primary cultures
      of equine skeletal muscle from control, heterozygous HyperPP, and homozygous
      affected HyperPP horses. There was a 10-fold lower level of HSL transcript in
      both undifferentiated and differentiated cultures from homozygous-affected horses
      than from horses of the other genotypes. Phenytoin selectively increased the HSL
      transcript in homozygous-affected differentiated cultures to levels similar to
      those of the other genotypes. The levels of CPT and FABP transcripts were
      unaffected by genotype, differentiation, and phenytoin treatment. These results
      suggest that the primary defect in HyperPP may secondarily decrease HSL
      transcript levels and that the therapeutic action of phenytoin may include
      regulation of mRNA transcripts in skeletal muscle.

PMID- 9784239
TI  - Identification of a new cytochrome P450 family, CYP45, from the lobster, Homarus
      americanus, and expression following hormone and xenobiotic exposures.
AB  - A new cytochrome P450, the first member of the CYP45 family, was identified from
      the hepatopancreas of the American lobster, Homarus americanus. The lobster CYP45
      shares significant sequence homologies to the vertebrate CYP3 and the
      invertebrate CYP6, CYP9, CYP28, and CYP30 families, perhaps indicating a common
      ancestor of these P450s. Of seven tissues examined, CYP45 was expressed only in
      the hepatopancreas, the crustacean equivalent of the vertebrate liver, pancreas,
      and intestine. Over the course of the lobster molt cycle, CYP45 expression
      mirrored the hemolymph titer of ecdysteroids, suggesting its potential
      involvement in molting hormone dynamics. This idea was strengthened further by
      ecdysteroid treatment of intermolt-stage lobsters during the lowest hemolymph
      titers and CYP45 expression levels. Significant elevations in hepatopancreas
      CYP45 mRNA levels were elicited by such injections over a 2- to 4-day interval.
      Similar experiments were performed by intubating juvenile lobsters with various
      xenobiotics. Induction of CYP45 expression occurred following phenobarbital and
      heptachlor administration, but not by beta-naphthoflavone. Hormonal and
      xenobiotic modulation of lobster CYP45 expression provides a potential pathway
      for endocrine disruption in lobsters.

PMID- 9784240
TI  - Stability of the Escherichia coli ATP synthase F0F1 complex is dependent on
      interactions between gamma Gln-269 and the beta subunit loop beta Asp-301-beta
      Asp-305.
AB  - The role of the conserved sequence motif 301DDLTDP306 in the F0F1 ATP synthase
      beta subunit was assessed by mutagenic analysis in the Escherichia coli enzyme.
      Mutations gave variable effects on F1 sector activity, stability, and membrane
      binding to the F0 sector. Upon solubilization, F1 sectors of the betaD302E and
      betaD305E mutants (betaAsp-302 and betaAsp-305 replaced by glutamate) dissociated
      into subunits, while mutants with other beta305 substitutions failed to assemble.
      Membrane ATPase activities of beta301 and 302 mutants were 20-70% of wild type.
      Replacements of the gamma subunit Gln-269 had similar effects. The membrane
      ATPase activities of the gammaQ269E or gammaQ269D mutants were significantly
      lower and their F1 sectors dissociated into subunits upon solubilization. These
      results suggest that the beta301-305 loop and the gamma subunit region around Gln
      269 form a key region for the assembly of alpha3 beta3 gamma complex. These
      results are consistent with the X-ray crystallographic structure of bovine F1 (J.
      P. Abrahams, A. G. W. Leslie, R. Lutter, and J. E. Walker (1994) Nature 370, 621
      628) where the beta301DDLTD305 loop directly interacts with gammaGln-269.

PMID- 9784241
TI  - Binding of the cysteine proteinases papain and cathepsin B-like to coated
      laminin: use of synthetic peptides from laminin and from the laminin binding
      region of the beta 1 integrin subunit to characterize the binding site.
AB  - Cysteine proteinases of the papain superfamily, i.e., papain and cathepsin B-like
      proteinase, were found to be able to bind to laminin-coated wells. When papain
      and cathepsin B-like proteinase were used, saturable binding curves were found.
      The characterization of the binding site was carried out using synthetic peptides
      which corresponded to the most relevant functional sites of laminin and an
      octapeptide from the laminin binding region of the beta1 integrin subunit. In
      binding experiments, the decapeptide RNIAEIIKDI and the pentapeptide YIGSR were
      able to displace papain and cathepsin B-like proteinase from coated laminin.
      Nevertheless, the integrin beta1 peptide DLYYLMDL was the most powerful in the
      same experimental system. From these results, the C-terminal region of this cross
      shaped protein, i.e., the end of the long arm, and the region including the YIGSR
      sequence of the short arm of the beta chain would be the cysteine proteinase
      binding site. This binding site is probably the result of the network
      organization of laminin which brings two regions, separated on a single laminin
      molecule, into proximity. In previous work, digestion of basement membranes has
      been found to be associated with the binding of cysteine proteinases to these
      supramolecular structures [N. Guinec, V. Dalet-Fumeron, and M. Pagano (1992) FEBS
      Lett. 308, 305-308]. The present report demonstrates that laminin is the cysteine
      proteinase binding protein of basement membranes. This property of laminin could
      be associated with tumor invasion and other tissue remodeling processes linked to
      proteolysis of basement membranes and extracellular matrices.

PMID- 9784242
TI  - Oxidative stress causes intracellular reversible S-thiolation of chicken
      hemoglobin under diamide and xanthine oxidase treatment.
AB  - Time courses of total (GSH-t), disulfide (GSSG), and mixed disulfide (PSSG) forms
      of glutathione were studied in chicken blood submitted to oxidative stress
      induced by diamide or by the reactive oxygen species (ROS)-producing system
      xanthine/xanthine oxidase (X/XO). Diamide-treated blood induced an immediate
      increase in GSSG and PSSG, while X/XO produced a slow and sustained stress with
      increased values of GSSG and PSSG only after 30 and/or 60 min of incubation. Both
      total protein S-thiolation (mixed disulfide with glutathione) and dethiolation
      and hemoglobin A S-thiolation and dethiolation were clearly observed. Hemoglobin
      A (Hb A) was the major S-thiolated protein. We further characterized chicken Hb S
      thiolation through the reaction of Hb with GSSG or the GSH/GSSG redox couple.
      Methemoglobin levels did not change with diamide or with X/XO treatment. Present
      results suggest that the most reactive cysteine pair of Hb A, the major chicken
      Hb, might function as an antioxidant under in vivo oxidative stress conditions.

PMID- 9784243
TI  - Site-specific mutations of conserved residues in the phosphate-binding loop of
      the Arabidopsis UMP/CMP kinase alter ATP and UMP binding.
AB  - All eukaryotic UMP/CMP kinases contain a glycine-rich sequence GGPG(S/A)GK at the
      N-terminus. This sequence is homologous to the conserved sequence GXXGXGK found
      in other ATP-binding proteins. To study the role of this conserved sequence in
      Arabidopsis UMP/CMP kinase, five conserved residues were mutated by site-directed
      mutagenesis to generate seven mutant enzymes: G21A, G22A, G24A, G26A, K27R, K27M,
      and K27E. The G21A and G26A mutants were degraded during the purification phase
      and were thus unable to be purified. Kinetic studies on the other mutants, when
      compared to studies on the wild-type enzyme, revealed that this sequence is
      important for ATP binding and enzyme catalysis. All mutants had a decreased
      kcat/KATPm value. The G22A and G24A mutants had about half of the kcat value of
      wildtype and 3.9-fold and 3.3-fold increases in KATPm values, respectively. The
      kcat/KATPm values in the K27M and K27E mutants were changed significantly and
      decreased by 1000-fold and 2600-fold, respectively. The removal of the terminal
      positive charge of Lys27 in the K27M and K27E mutants resulted in 20% of the kcat
      value of wildtype. However, both mutants had a remarkable increase in KATPm value
      by 241-fold and 552-fold, respectively. Therefore, the positive charge of Lys27
      plays an important role on both ATP binding and enzyme catalysis. Interestingly,
      the results also showed that the mutations that affected ATP binding also had an
      effect on UMP binding.

PMID- 9784244
TI  - Transfer of two oligosaccharides to protein in a Chinese hamster ovary cell B211
      which utilizes polyprenol for its N-linked glycosylation intermediates.
AB  - B211, a glycosylation mutant isolated from Chinese hamster ovary cells,
      synthesizes 10- to 15-fold less Glc3Man9GlcNAc2-P-P-lipid, the substrate used by
      the oligosaccharide transferase in the synthesis of asparagine-linked
      glycoproteins. B211 cells are also 10- to 15-fold deficient in the glucosylation
      of oligosaccharide-lipid. Despite these properties, protein glycosylation in B211
      cells proceeds at a level similar to (50% of) parental cells. We asked whether
      the near wild-type level of glycosylation was due to the transfer of alternative
      oligosaccharide structures to protein in B211 cells. The aberrant size of
      [35S]methionine-labeled VSV G protein and the increased percentage of
      endoglycosidase H-resistant tryptic peptides as compared to parental cells
      supported this hypothesis. B211 cells were labeled with [2-3H]mannose either for
      1 min or for 1 h in the presence of glycoprotein-processing inhibitors so that
      the oligosaccharides initially transferred to protein could be analyzed. In
      addition to Glc3Man9GlcNAc2, a second, endoglycosidase H-resistant
      oligosaccharide was transferred whose structure was determined by alpha
      mannosidase digestion, gel filtration chromatography, and HPLC to be
      Glc0,1Man5GlcNAc2. Finally, since the synthesis of reduced amounts of
      Glc3Man9GlcNAc2-P-P-lipid was also a phenotype seen in another glycosylation
      mutant, Lec9, we analyzed the long-chain prenol in B211 cells. B211 cells
      synthesized and utilized polyprenol rather than dolichol for all N-linked
      glycosylation intermediates as determined by HPLC analysis of [3H]mevalonate
      labeled lipids. Cell fusions analyzed by similar techniques indicated that B211,
      originally isolated as a concanavalin A-resistant cell line, is in the Lec9
      complementation group.

PMID- 9784245
TI  - Cardiac myosin-binding protein C (MyBP-C): identification of protein kinase A and
      protein kinase C phosphorylation sites.
AB  - Myosin binding protein C (MyBP-C) is a major myofibril-associated protein in
      cardiac muscle which is subject to reversible phosphorylation. Cardiac MyBP-C is
      a substrate in vivo and in vitro for cAMP-dependent protein kinase (PKA) and
      calcium/phospholipid-dependent protein kinase (PKC). Chicken cardiac MyBP-C was
      phosphorylated by PKA to 3.0 mol phosphate/mol and by PKC to 2.0 mol
      phosphate/mol. Tryptic phosphopeptides from MyBP-C were purified by successive
      iron iminodiacetate column chromatography and reversed-phase high-performance
      liquid chromatography. Three phosphopeptides purified from PKA-phosphorylated
      MyBP-C contained phosphoserine [T1, (RTS[P]LAGGGR) and T2, (KRDS[P]FLR)] or
      phosphothreonine (CT3, MT[P]SAFL). PKC phosphorylated two of the same sites (T1
      and T2) as PKA and an additional site [T2a (TGTTYKPPS[P]YK)]. PKA phosphorylation
      sites corresponding to peptides T1, T2, and T3 were identified in the N-terminus
      of the cDNA deduced amino acid sequence (S265, S300, and T274, respectively). The
      PKC-specific site in peptide T2a was at position S1169. cDNA clones encoding rat
      cardiac MyBP-C were isolated, and the segment corresponding to PKA and major PKC
      phosphorylation sites was sequenced. Chicken cardiac MyBP-C has a threonine at
      position 274 (CT3), whereas rat cardiac MyBP-C has a serine at the corresponding
      position. Only chicken cardiac MyBP-C had a phosphorylatable residue at the
      position corresponding to S1169. All of the cardiac MyBP-C phosphorylation sites
      are absent in known sequences of skeletal muscle MyBP-C isoforms.

PMID- 9784246
TI  - In vitro generation of an active calmodulin-independent phosphodiesterase from
      brain calmodulin-dependent phosphodiesterase (PDE1A2) by m-calpain.
AB  - In the present study we have shown that bovine brain 60-kDa calmodulin-dependent
      cyclic nucleotide phosphodiesterase isozyme (CaMPDE - PDE1A2) is proteolyzed by a
      Ca2+-dependent cysteine protease, m-calpain. The proteolysis of PDE1A2 by m
      calpain results in its conversion to a totally calmodulin (CaM)-independent form
      accompanied by degradation of PDE1A2 into a 45-kDa catalytic fragment and a 15
      kDa fragment. The activity of PDE1A2 is unaffected by the presence or absence of
      CaM during cleavage, suggesting that the interaction between CaM and PDE1A2 does
      not alter substrate recognition by calpain. Furthermore, we provide evidence,
      based on the studies of CaM overlay and phosphorylation, that the cleavage site
      is not present either in the CaM-binding domain or phosphorylation site. N
      terminal sequence analysis of the 45-kDa fragment indicated that cleavage occurs
      between residues 126Gln and 127Ala, and eliminates the CaM-dependent activity of
      carboxy termini PDE1A2. The present findings suggest that limited proteolysis in
      the brain through calpains could be an alternate mechanism for activating
      CaMPDE(s) and for regulating intracellular levels of cAMP.

PMID- 9784247
TI  - Species differences in L-tryptophan-kynurenine pathway metabolism: quantification
      of anthranilic acid and its related enzymes.
AB  - Anthranilic acid (AA) has attracted considerable attention as one of the L
      tryptophan-kynurenine pathway metabolites in the central nervous system. In this
      study, a highly sensitive and accurate method for the quantification of AA has
      been developed using reversed-phase high-performance liquid chromatography with
      electrochemical detection. Serum and cerebrospinal fluid (CSF) AA concentrations
      in different animal species were measured. CSF AA concentrations in rabbits were
      1.1 +/- 0.1 nmol/liter, which were 5. 7-33.0 times lower than those in other
      species studied. Serum AA concentrations, however, were slightly higher in
      rabbits than in other species. In contrast, the concentrations of L-kynurenine (L
      KYN) in both serum and CSF were substantially higher in rabbits than in other
      species. Tissue kynurenine pathway enzymes, indoleamine 2,3-dioxygenase (IDO),
      tryptophan 2,3-dioxygenase, kynurenine 3-hydroxylase, and kynureninase were
      determined in rabbits, rats, gerbils, and mice. These enzymes varied among
      species, especially lung IDO activities in rabbits were 146-516 times higher than
      those found in other species, but rabbit liver kynurenine 3-hydroxylase
      activities were lower by one order of magnitude than those of the other species
      tested. Furthermore, brain kynurenine 3-hydroxylasae activities were 12.3-23.2
      times higher in gerbils than those in the other species tested. In addition, AA
      concentrations in serum following intravenous administration of L-KYN (5 mg/kg)
      were also measured in rabbits. AA levels peaked sharply within 5 min after
      administration and decreased in a time-dependent manner. At 5 min after
      administration, CSF L-KYN and AA concentrations were also increased by 1.76- and
      2.56-fold, respectively, compared with basal levels. Increased AA concentrations
      in CSF following L-KYN administration may reflect the entry of AA into the CSF
      after conversion to AA in systemic tissue and/or the local synthesis of AA from L
      KYN in the CNS.

PMID- 9784249
TI  - Immunochemical characterization and role in toxic activities of region 115-129 of
      myotoxin II, a Lys49 phospholipase A2 from Bothrops asper snake venom.
AB  - The region 115-129 of myotoxin II, a catalytically inactive Lys49 phospholipase
      A2, was previously shown to constitute a heparin-binding site and to be involved
      in its cytolytic action in vitro. An immunochemical approach was utilized to
      further explore the role of this region in the toxic activities of myotoxin II.
      By using a carrier-linked 13-mer synthetic peptide as immunogen, rabbit
      polyclonal antibodies against region 115-129 were obtained. These antibodies were
      able to bind to the native protein and to inhibit its myotoxic and cytolytic
      effects in preincubation-type neutralization experiments. Antibodies to peptide
      115-129 formed precipitating macromolecular complexes in gel immunodiffusion,
      demonstrating the oligomeric state of myotoxin II not only in its crystalline
      structure (dimeric), but also in solution. Analyses of the antibody response to
      carrier-linked peptide 115-129 and native myotoxin II suggest that region 115
      129, although potentially immunogenic, is not an immunodominant B-cell epitope of
      this protein, failing to elicit significant antibody responses in animals
      immunized with the native toxin. Antibodies to peptide 115-129 cross-reacted with
      15 purified class II myotoxic phospholipases A2 found in snake venoms of the
      genera Bothrops, Agkistrodon, Trimeresurus, and Vipera, but not with the
      recombinant human class II phospholipase A2, for which no toxic actions have been
      described. Myotoxic phospholipases of the class I (notexin) and class III (bee
      venom) groups were not recognized by antibodies to p115-129. These results
      demonstrate that the overall antigenic structure of region 115-129 is conserved
      among class II myotoxic phospholipases A2, despite differences in their
      corresponding amino acid sequences. Based on the accumulated experimental
      evidence, a model of the myotoxic region of myotoxin II, and possibly of related
      class II Lys49 phospholipase A2 myotoxins, is proposed.

PMID- 9784248
TI  - Capsaicin-responsive NADH oxidase activities from urine of cancer patients.
AB  - NADH oxidases of low specific activities from urine of cancer patients were found
      to be inhibited or stimulated by the vanilloid capsaicin (8-methyl-N-vanillyl-6
      noneamide). Similar activities, inhibited or stimulated by capsaicin, were
      reported previously for sera of cancer patients but not for sera of normal
      volunteers or for patients with disorders other than cancer. Like those from
      sera, the activities from urine were resistant to heat and to digestion with
      proteinase K. Two different fractions with capsaicin-responsive NADH oxidase
      activities were obtained by FPLC. One fraction in which the 33-kDa band was the
      major component exhibited NADH oxidase activity stimulated by capsaicin. Another
      fraction in which 66-kDa and 45-kDa bands were major components exhibited NADH
      oxidase activities inhibited by capsaicin. A monoclonal antibody generated to a
      ca 34-kDa form of the NADH oxidase from sera reacted with a urine protein of a ca
      33-kDa band in the capsaicin-stimulated fraction. The 33-kDa protein was of low
      abundance and was estimated to be present in amounts between 5 and 100
      microgram/L, depending on the particular patient.

PMID- 9784250
TI  - Induction of cytochrome P-450 1A1 by omeprazole in human HepG2 cells is protein
      tyrosine kinase-dependent and is not inhibited by alpha-naphthoflavone.
AB  - Benzimidazole compounds, such as omeprazole and thiabendazole, are a different
      type of CYP1A1 inducer from Ah receptor-ligands, such as TCDD (2,3,7,8
      tetrachlorodibenzo-p-dioxin) and 3-methylcholanthrene. In HepG2 cells, the
      commonly used tyrosine kinase inhibitors, herbimycin-A and a series of
      tyrphostins, inhibited the induction of CYP1A1 produced by treatment with TCDD.
      Genistein, another type of tyrosine kinase inhibitor, inhibited the induction of
      CYP1A1 whether it was produced by omeprazole or TCDD; however, this inhibition
      was caused by a dual effect of genistein, that is an anti-tyrosine kinase and an
      anti-topoisomerase I effect. An antagonist of Ah receptor, alpha-naphthoflavone
      (0.1-10 microM), and 3'-methoxy-4'-aminoflavone (1 microM), did not inhibit the
      induction of CYP1A1 produced in HepG2 cells by omeprazole, but both of them did
      inhibit that produced by TCDD. In one of a number of human lung tumor cell lines,
      S6T, the inducibility of CYP1A1 was high by TCDD, whereas the inducibility by
      omeprazole was low. Thus, omeprazole appears to induce CYP1A1 by initiating a
      protein tyrosine kinase-mediated signal transduction pathway, a different pathway
      from that inhibited by TCDD.

PMID- 9784251
TI  - Metmyoglobin/fluoride: effect of distal histidine protonation on the association
      and dissociation rate constants.
AB  - The kinetics of formation and dissociation of the horse metmyoglobin/fluoride
      complex has been investigated between pH 3.4 and 11. The ionic strength
      dependence of the reaction has been measured at integral pH values between pH 5
      and 10. Hydrofluoric acid, HF, binds to metmyoglobin with a rate constant of (4.7
      +/- 0. 7) x 10(4) M-1 s-1. An apparent ionization in metmyoglobin with a pKa of
      4.4 +/- 0.5 influences the rate of HF binding and is attributed to the distal
      histidine, His-64. Protonation of His-64 increases the HF binding rate by a
      factor of 2.6. The fluoride anion, F-, binds to metmyoglobin with a rate constant
      of (5.6 +/- 1.4) x 10(-2) M-1 s-1, about 10(6) times slower than HF. Binding of
      either HF or F- to hydroxymetmyoglobin cannot be detected. Protonation of the
      distal histidine facilitates HF dissociation from the metmyoglobin/fluoride
      complex. HF dissociates with a rate constant of 1.9 +/- 0.3 s-1. The fluoride
      anion dissociates 2000 times more slowly, with a rate constant of (8.7 +/- 1.6) x
      10(-4) s-1. The apparent pKa for His-64 ionization in the fluorometmyoglobin
      complex is 5.7 +/- 0.1. The association and dissociation rate constants are
      relatively independent of ionic strength with secondary kinetic salt effects
      sufficient to account for the ionic strength variation of both, consistent with
      the idea that association and dissociation of neutral HF dominate the kinetics of
      fluoride binding to metmyoglobin.

PMID- 9784252
TI  - Activation of horse liver alcohol dehydrogenase upon substitution of tryptophan
      314 at the dimer interface.
AB  - Horse liver alcohol dehydrogenase contains two tryptophan residues per subunit,
      Trp-15 on the surface of the catalytic domain and Trp-314 buried in the interface
      between the subunits of the dimer. We studied the contributions of the
      tryptophans to fluorescence and catalytic dynamics by substituting Trp-314 with a
      leucine residue and making two compensatory mutations that were required to
      obtain a stable protein, leading to the triple mutant M303F-L308I-W314L enzyme.
      The substitutions increased by two- to sixfold the turnover numbers for ethanol
      oxidation, acetaldehyde reduction, and the dissociation constants of the
      coenzymes. The rate of the exponential burst phase for the transient oxidation of
      ethanol increased slightly, but the rate of dissociation of the enzyme-NADH
      complex still limited turnover of ethanol, as for wild-type enzyme. The three
      substitutions at the dimer interface apparently activate the enzyme by allowing
      more rapid conformational changes that accompany coenzyme binding, probably due
      to movement of the loop containing residues 293 to 298. The emission spectrum of
      M303F-L308I-W314L enzyme, which contains Trp-15, was redshifted compared to wild
      type enzyme. Time-resolved fluorescence measurements with the triple mutant show
      that the decay of Trp-15 is dominated by a approximately 7-ns component. In the
      mutant enzyme with Trp-15 substituted with phenylalanine, the decay of Trp-314 is
      dominated by a approximately 4-ns component. Solute quenching data for wild-type
      enzyme and the mutants show that only Trp-15 is exposed to iodide and acrylamide,
      whereas Trp-314 is inaccessible. The luminescence properties of the tryptophan
      residues in the mutated enzymes are consistent with conclusions from studies of
      the wild-type enzyme [M. R. Eftink, 1992, Adv. Biophys. Chem. 2, 81-114].

PMID- 9784254
TI  - Release of two peripheral proteins from chloroplast thylakoid membranes in the
      presence of a Hofmeister series of chaotropic anions.
AB  - The dissociation of two peripheral spinach (Spinacia oleracea L.) thylakoid
      membrane proteins, coupling factor CF1 and ferredoxin-NADP+-oxidoreductase, in
      the presence of chaotropic sodium salts has been investigated, using monospecific
      antibodies against the proteins as probes. Release of both proteins followed the
      Hofmeister series of anions (Cl- < NO3- < Br- < I- < SCN-). In mixtures, the
      different salts had an additive effect. In addition, there were also qualitative
      differences in the action of the anions, such that NaI and NaSCN led to a
      different concentration and time dependence of the dissociation of the peripheral
      proteins from thylakoids. An analysis of the temperature dependence of protein
      release showed that the more chaotropic ions reduced the activation energy
      required for the dissociation of the proteins from their binding sites on the
      membrane. The addition of sugars (glucose, sucrose, or trehalose) reduced the
      amount of protein released from the membranes in the presence of NaI or NaSCN.

PMID- 9784255
TI  - Fatty acid pattern of human prostasome lipid.
AB  - Prostasomes are organelles of prostatic origin found in human semen. Their
      average diameter is about 150 nm and they appear as a lipoprotein membrane
      surrounding less organized material. Their lipid composition is peculiar, having
      much cholesterol and sphingomyelin. On the other hand, many of their proteins
      possess catalytic activity and are involved in the immune response. In previous
      work, we have shown that prostasomes may fuse to sperm at slightly acidic pH
      values, thereby modifying the composition of the sperm plasma membrane. In this
      paper, we examine the fatty acid pattern of prostasome lipid and find that it is
      completely different from that of sperm membrane lipid. Polyunsaturated
      phosphatidylcholines, common in sperm membrane, are rare in prostasome.
      Therefore, the fusion between prostasomes and sperm should stabilize sperm plasma
      membrane by enriching it in cholesterol, sphingomyelin, and saturated
      glycerophospholipid. This would prevent the untimely occurrence of the acrosome
      reaction.

PMID- 9784253
TI  - Identification of Asp95 as the site of succinimide formation in recombinant human
      glial cell line-derived neurotrophic factor.
AB  - Human glial cell line-derived neurotrophic factor is a single polypeptide of 134
      amino acids and functions as a disulfide-linked dimer. Incubation of the protein
      in pH 5.0 and at 37 degreesC for 1 week showed that 5% of the material was
      converted to a form that eluted after the major protein peak on a cation-exchange
      column. The modified component gave an average molecular mass of 30367.0 u
      (theoretical = 30384.8 u). Within measurement error, this 17.8-u decrease in mass
      indicated the loss of a water molecule. This observation, together with the
      protein's behavior on cation-exchange chromatography and the mode of incubation
      used to generate the modification, was consistent with cyclic imide (succinimide)
      formation at an aspartyl residue. Hence, only a monomer of the dimeric protein
      was modified. The modified monomer was purified and subjected to peptic
      degradation. By a combination of N-terminal analysis and mass spectrometry, the
      region containing Asp95-Lys96 was identified to be modified. This was further
      confirmed by carboxypeptidase Y digestion of the modified peptide where the
      modified region was found to be resistant to further enzymatic degradation.
      Furthermore, incubation of the modified monomer in pH 8. 5 for 2 h yielded two
      peaks, in agreement with the succinimide model where the cyclic imide was
      hydrolyzed into a mixture of isoaspartate and aspartate. Tryptic mapping of the
      isoaspartyl-containing protein showed that Asp95 was refractory to Edman
      degradation, confirming it was in the isoaspartate form. Hence, the modification
      observed was due to succinimide formation at Asp95. This is the first report of
      succinimide formation at an Asp-Lys linkage.

PMID- 9784270
TI  - Structural prominence and agrammatic theta-role assignment: a reconsideration of
      linear strategies.
AB  - In this paper we examine the tendency for agrammatic aphasics to make thematic
      reversal errors in comprehension, e.g., a tendency for English-speaking
      agrammatics to assign a preposed object the subject role. Although this tendency
      has been argued to follow from either a linear (Grodzinsky, 1995) or a
      directionality (Hagiwara & Caplan, 1990) strategy, we show that such proposals
      can, at best, function as language-particular strategies. We examine data from
      English, Japanese, German and Dutch, and propose a Structural Prominence
      Hypothesis which captures the following cross-linguistic generalization: thematic
      reversal errors result from a tendency to assign thematic roles based on the
      relative structural prominence of the candidate NPs.

PMID- 9784271
TI  - Hemispheric organization of local- and global-level visuospatial processes in
      deaf signers and its relation to sign language aphasia.
AB  - Previous work has shown that deficits in the production and perception of signed
      language are linked to left hemisphere damage but not right hemisphere damage in
      deaf lifelong signers, whereas severe deficits in nonlinguistic visuospatial
      abilities are more frequent following right hemisphere damage than left
      hemisphere damage in this population. In the present study we investigated the
      extent to which sign language deficits in deaf individuals can be dissociated
      from more subtle visuospatial deficits commonly associated with left hemisphere
      damage in the hearing/speaking population. A group of left- or right-lesioned
      deaf signers were asked to reproduce (1) two line drawings (a house and an
      elephant) and (2) four hierarchical figures. Drawings were scored separately for
      the presence of local vs global features. Consistent with data from hearing
      patients, left hemisphere-damaged deaf subjects were significantly better at
      reproducing global-level features, whereas right hemisphere-damaged deaf subjects
      were significantly better at reproducing local-level features. This effect held
      for both types of stimuli. Local-level performance in the LHD group did not
      correlate with performance on sign language tasks, suggesting that language
      deficits in LHD deaf signers are in fact linguistic specific.

PMID- 9784272
TI  - Bilingual aphasia: semantic organization, strategy use, and productivity in
      semantic verbal fluency.
AB  - A semantic verbal fluency task (Animals, Foods) was administered to 16 aphasic,
      bilingual adults in French and English. Each subject was tested twice in each
      language. The two goals of the study were to compare performance across languages
      and to determine the effect of a deliberate grouping strategy on productivity.
      All subjects claimed approximately equal prestroke abilities in both languages.
      The number of words subjects produced was not significantly different in the two
      languages. Semantic organization across languages was also similar on Test 1. On
      Test 2, 8 subjects were instructed to group items by subcategory and 8 simply
      repeated the task. There was no consistent between-group difference in number of
      correct words or in the semantic organization of responses. Implications for the
      clinical use of verbal fluency tests and for further research into bilingual
      lexicosemantic systems are discussed.

PMID- 9784273
TI  - Hemispheric involvement in the perception of syntactic prosody is dynamically
      dependent on task demands.
AB  - The first aim of this study was to determine if there was a significant
      perceptual asymmetry for syntactic prosody and if it differed from the perceptual
      asymmetry for emotional prosody. The second aim of this study was to determine if
      the observed asymmetries were the product of task demands or stimulus features.
      Experiment 1 consisted of a Syntactic task and an Emotional task. In the
      Syntactic task, subjects identified Statement and Question prosody in
      dichotically presented sentences. In the Emotional task, subjects identified
      Angry and Sad prosody in dichotically presented sentences. There was a
      significant left ear advantage for the Emotional task and no significant ear
      advantage for the Syntactic task. In Experiment 2, subjects had to perform an
      Emotional prosody task with the syntactic Statement and Question prosody stimuli
      from Experiment 1. There was a significant left ear advantage, indicating that
      the perceptual asymmetry was determined by task demands and not stimulus
      features.

PMID- 9784274
TI  - Priming and aging: an electrophysiological investigation of N400 and recall.
AB  - Twenty young (20.5 years) and 20 middle-aged academics (57.2 years) performed a
      priming-recall task which was presented in three blocks. In each block,
      participants read 40 word pairs after which a recall task had to be carried out.
      Half of the word pairs were highly associated while the others were low
      associated. Targets showed the N400 of the middle-aged group to be both delayed
      and smaller in amplitude for low-associated items. N400 of primes, however,
      showed no age-related latency difference but was smaller for the middle-aged
      group due to a positive shift. It is argued that this shift possibly indicates
      age differences in semantic activation or buildup of context. A reanalysis showed
      individual differences in word pair processing to depend on recall performance.
      In general, high recallers were found to show a much larger differentiation
      between low- and high-associated targets. This resulted from a much larger N400
      component elicited by low-associated targets and a more positive ERP in the N400
      region for the high-associated targets. It is suggested that the middle-aged
      subjects activated the expected target word to a level at least equivalent to the
      younger subjects, but that the activated network itself was larger/less selective
      particularly in subjects showing a low recall.

PMID- 9784275
TI  - Stories about hands, brains, and minds.
AB  - The "extreme" versus "mild" classification of handedness of Natsopoulos et al.
      (1998) is not comparable to that of Annett (review, 1995) because 50% of the
      former sample were left-handers while the samples of the latter were unselected
      for handedness. The 20% of the Natsopoulos sample called "extreme" right-handers
      represent nearly 40% of the general population. The possibility cannot be ruled
      out that the advantage for right-handers in this sample was due to a small excess
      of disabled children among left-handers because there were no controls for hand
      skill or for reading ability.

PMID- 9784277
TI  - Induction of the 27-kDa heat shock protein (Hsp27) in the rat medulla oblongata
      after vagus nerve injury.
AB  - The 27-kDa heat shock protein (Hsp27) is constitutively expressed in motor and
      sensory neurons of the brainstem. Hsp27 is also rapidly induced in the nervous
      system following oxidative and cellular metabolic stress. In this study, we
      examined the distribution of Hsp27 in the rat medulla oblongata by means of
      immunohistochemistry after the vagus nerve was cut or crushed. After vagal
      injury, rats were allowed to survive for 6, 12, 24 h, 2, 4, 7, 10, 14, 30, or 90
      days. Vagus nerve lesions resulted in a time-dependent up-regulation of Hsp27 in
      vagal motor and nodose ganglion sensory neurons that expressed Hsp27
      constitutively and de novo induction in neurons that did not express Hsp27
      constitutively. In the dorsal motor nucleus of the vagus nerve (DMV) and nucleus
      ambiguus, the levels of Hsp27 in motor neurons were elevated within 24 h of
      injury and persisted for up to 90 days. Vagal afferents to the nucleus of the
      tractus solitarius (NTS) and area postrema showed increases in Hsp27 levels
      within 4 days that were still present 90 days postinjury. In addition, increases
      in Hsp27 staining of axons in the NTS and DMV suggest that vagus nerve injury
      resulted in sprouting of afferent axons and spread into areas of the dorsal vagal
      complex not normally innervated by the vagus. Our observations are consistent
      with the possibility that Hsp27 plays a role in long-term survival of distinct
      subpopulations of injured vagal motor and sensory neurons.

PMID- 9784278
TI  - Localization of metallothionein-I and -III expression in the CNS of transgenic
      mice with astrocyte-targeted expression of interleukin 6.
AB  - The effect of interleukin-6 (IL-6) on metallothionein-I (MT-I) and MT-III
      expression in the brain has been studied in transgenic mice expressing IL-6 under
      the regulatory control of the glial fibrillary acidic protein gene promoter (GFAP
      IL6 mice), which develop chronic progressive neurodegenerative disease. In situ
      hybridization analysis revealed that GFAP-IL6 (G16-low expressor line, and G36
      high expressor line) mice had strongly increased MT-I mRNA levels in the
      cerebellum (Purkinje and granular layers of the cerebellar cortex and basal
      nuclei) and, to a lesser degree, in thalamus (only G36 line) and hypothalamus,
      whereas no significant alterations were observed in other brain areas studied.
      Microautoradiography and immunocytochemistry studies suggest that the MT-I
      expression is predominantly localized to astrocytes throughout the cerebrum and
      especially in Bergman glia in the cerebellum. However, a significant expression
      was also observed in microglia of the GFAP-IL6 mice. MT-III expression was
      significantly increased in the Purkinje cell layer and basal nuclei of the
      cerebellum, which was confirmed by Northern blot analysis of poly(A)+ mRNA and by
      ELISA of the MT-III protein. In contrast, in the G36 but not G16 mice, transgene
      expression of IL-6 was associated with significantly decreased MT-III RNA levels
      in the dentate gyrus and CA3 pyramidal neuron layer of the hippocampus and, in
      both G36 and G16 mice, in the occipital but not frontal cortex and in ependymal
      cells. Thus, both the widely expressed MT-I isoform and the CNS specific MT-III
      isoform are significantly affected in a MT isoform- and CNS area-specific manner
      in the GFAP-IL6 mice, a chronic model of brain damage.

PMID- 9784279
TI  - Glial cell line-derived neurotrophic factor improves survival of dopaminergic
      neurons in transplants of fetal ventral mesencephalic tissue.
AB  - This study was designed to determine whether or not an exogenous source of glial
      cell line-derived neurotrophic factor (GDNF) could be delivered continuously into
      the denervated/transplanted striatum and stimulate the survival, growth, and
      function of fetal ventral mesencephalic tissue transplants. Adult male rats with
      unilateral 6-hydroxydopamine lesions received transplants of fetal ventral
      mesencephalic tissue into the denervated striatum. Immediately thereafter,
      osmotic pumps [Alzet 2002, 0.5 microliter/h] were attached to intracerebral
      cannula and either a citrate buffer alone [control] or r-methuGDNF [dissolved in
      sodium citrate buffer to a concentration of 0.45 microgram/microliter] was
      infused into a site approximately 1.0 mm lateral to the transplant for a 2-week
      period; one group of lesioned animals did not receive transplants but was infused
      with GDNF. The effect of GDNF on tyrosine hydroxylase-positive (TH+) fiber
      outgrowth from transplants was variable, and image analysis revealed no
      significant difference between the GDNF and citrate groups. In contrast, the mean
      number of TH+ cells bodies in transplants infused with GDNF [2,037 +/- 149, n =
      8] vs citrate [663 +/- 160, n = 8] was statistically significant (P < 0.001);
      cell counts were made in every third brain section [35 micrometer]. Similarly,
      transplants infused with GDNF showed an over-compensatory effect to amphetamine
      induced rotational behavior that was significantly lower than that observed in
      transplanted animals receiving citrate buffer infusions. Infusions of GDNF into
      the denervated striatum alone had no significant effect on amphetamine-induced
      rotational behavior or on TH fiber morphology in the lesioned striatum. Thus, a
      continuous infusion of GDNF can improve the survivability of dopaminergic neurons
      in transplants of fetal ventral mesencephalic tissue.

PMID- 9784280
TI  - Focal microinjection of gamma-acetylenic GABA into the rat entorhinal cortex:
      behavioral and electroencephalographic abnormalities and preferential neuron loss
      in layer III.
AB  - Neuron loss in layer III of the entorhinal cortex (EC) occurs in patients with
      temporal lobe epilepsy and in several animal models of the disease and may play a
      role in the development of spontaneously recurring seizures. This damage can be
      reproduced in rats by a focal microinjection of the indirect excitotoxin
      aminooxyacetic acid into the EC (Neurosci. Lett., 147: 185, 1992). We have now
      examined a similar but approximately 20 times more potent toxin, gamma-acetylenic
      GABA (GAG), for its ability to produce seizures and neurodegeneration in the rat
      EC. EEG activity was recorded continuously for 48 h after a focal injection of 4
      micrograms GAG into the rat EC. Seizure episodes, spiking, and other
      irregularities occurred with a latency of 150 min. Behavioral abnormalities were
      observed in all animals and were always accompanied by EEG seizures. The
      behavioral changes subsided gradually, but EEG seizures continued up to 24 h
      after GAG treatment. Nissl and silver-stained tissue sections obtained 2-3 days
      after the injection of 4 micrograms GAG revealed neuron loss which preferentially
      affected the medial part of layer III of the EC, and caused a modest lesion in
      the hilar region of the ventral hippocampus. The neurodegenerative potency of
      GAG, in contrast to the effects of aminooxyacetic acid, was not influenced by the
      depth of anesthesia during surgery. A slight increase in the dose of GAG (to 5
      micrograms) resulted in more severe behavioral seizures, causing generalized
      convulsions with salivation and loss of righting posture in 3 of 13 rats. These
      animals also showed a marked enlargement of the lesioned area, with substantial
      neuronal loss occurring in layer III of the EC, in the hilus of the dentate
      gyrus, and occasionally also in homotopic structures of the contralateral
      hemisphere. Seizure activity and lesions induced by 4 micrograms GAG were
      prevented by the NMDA receptor antagonist Dizolcipine (MK-801) (4 mg/kg, i.p., 10
      min before and 12 h after GAG). These data support the notion of a close
      correlation between the occurrence of seizures and neuronal loss in layer III of
      the EC. Taken together, the study suggests that intraentorhinal injections of GAG
      may provide an advantageous model for the study of epileptogenic and epileptic
      mechanisms.

PMID- 9784281
TI  - Chronic exposure to MPTP as a primate model of progressive parkinsonism: a pilot
      study with a free radical scavenger.
AB  - The development of a validated primate model of progressive parkinsonism is a
      critical step in the evaluation of drugs that might halt or slow progression of
      Parkinson's disease. In this pilot study, we gradually exposed 14 cynomolgus
      monkeys to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), at a weekly dose
      of 0.5 mg/kg s.c. for 10 weeks, to determine their probability of not reaching a
      predetermined endpoint on a disability scale by Kaplan-Meier analysis. Four other
      MPTP-exposed animals were coadministered the potent free radical scavenger 7
      hydroxy-1-[4-(3-methoxyphenyl)-1-piperazinyl]acetylamino-2,2,4,6-
      tetramethylindan (OPC-14117) as a single oral daily dose of 0.6 g/kg, starting 2
      weeks before MPTP initiation. The risk of reaching endpoint by week 10 was 79%
      and mean time before reaching endpoint was 6 weeks. Global motor activity,
      recorded in a subset of animals using a portable activity monitor, declined
      following the first MPTP dose and never recovered. Several cerebrospinal fluid
      indices of central monoamine metabolism collected by suboccipital puncture at 0,
      5, and 10 weeks, including HVA, DOPAC, and tetrahydrobiopterin but not MHPG, were
      found to be "trait" markers for MPTP exposure, whereas CSF DOPAC and
      tetrahydrobiopterin constituted potential "state" markers for reaching endpoint.
      The antioxidant OPC-14117 did not protect against MPTP-induced parkinsonism.
      Further attempts to validate this incremental model of neurotoxin-induced
      parkinsonism as a predictor of patient responses to putative neuroprotective
      agents appear warranted.

PMID- 9784282
TI  - Hu23F2G, an antibody recognizing the leukocyte CD11/CD18 integrin, reduces injury
      in a rabbit model of transient focal cerebral ischemia.
AB  - Neutrophils are known to mediate injury in acute ischemic stroke especially
      during reperfusion. Migration of neutrophils into regions of ischemic injury
      involves binding to the endothelial cell's intercellular adhesion molecule (ICAM
      1) through the leukocyte integrin, CD11/CD18. We studied the potential for
      neuroprotection with a humanized antibody that binds to and blocks the functions
      of the CD11/CD18 integrin in a rabbit model of transient focal ischemia. Fifteen
      New Zealand White rabbits underwent transorbital occlusion of the left middle
      cerebral, anterior cerebral, and internal carotid arteries using aneurysm clips
      for 2 h, followed by 6 h of reperfusion. Treatment with a maximally saturating
      dose (4 mg/kg) of a humanized CD11/CD18 monoclonal antibody (Hu23F2G, ICOS Corp.,
      Bothell, WA) (n = 8) or placebo (n = 7) was administered 20 min after occlusion
      and given as a single intravenous bolus. Hemispheric ischemic neuronal damage
      (IND) as seen on hematoxylin- and eosin-stained sections was significantly
      reduced in Hu23F2G-treated animals by 57% (Hu23F2G: 15 +/- 6.9%; placebo: 35 +/-
      5%; mean +/- SEM, P < 0.05, t-test). Immunohistochemical staining with neutrophil
      elastase confirmed the presence of neutrophils within regions of IND in control
      brains. Treatment with Hu23F2G resulted in marked reduction of neutrophil
      infiltration. (No. of neutrophils/IND area: Hu23F2G 36.1 +/- 36.7 cm-2, placebo
      460.6 +/- 101.8 cm-2, P = 0.001. ) Antagonism of neutrophil migration at the
      level of the CD11/CD18 integrin reduces ischemic injury in experimental stroke.

PMID- 9784283
TI  - Glutamate receptor subunit GluR2 and NMDAR1 immunoreactivity in the retina of
      macaque monkeys with experimental glaucoma does not identify vulnerable neurons.
AB  - Excitatory amino acid neurotoxicity has been proposed as a mechanism underlying
      selective neuronal death in glaucoma. The relationships between the cellular
      distribution of glutamate receptor subunit proteins GluR2 and NMDAR1 and the
      vulnerability of restricted retinal neuron subpopulations was explored in
      experimental glaucoma in macaque monkeys, produced by treating the trabecular
      meshwork in one eye with argon or diode laser burns. Immunostaining of retinal
      segments was performed using specific monoclonal antibodies to the GluR2 and
      NMDAR1 subunit proteins as well as neurofilament protein. The distribution of
      immunoreactivity was qualitatively assessed in the retina, and ganglion cells
      were counted in the paracentral and peripheral regions of each retinal segment.
      Immunoreactivity for both of these glutamate receptor subunit proteins was widely
      distributed in most retinal neuron types in control eyes and was colocalized with
      neurofilament protein in ganglion cells. In the glaucomatous eyes, densities of
      GluR2- and NMDAR1-immunoreactive ganglion cells were dramatically reduced
      compared to unaffected fellow eyes, but GluR2- and NMDAR1-immunoreactive
      populations of horizontal, bipolar, and amacrine cells were not affected. These
      data parallel previous observations on the selective vulnerability of ganglion
      cells in this experimental model of glaucoma. However, GluR2 and NMDAR1 subunits
      do not constitute cell type-specific markers of vulnerability in glaucoma as they
      are present in neurons prone to degeneration as well as in resistant ones. While
      retinal pathology in glaucoma involves excitotoxic mechanisms that may be related
      to glutamate receptor subunits regulating calcium fluxes, the specific pattern of
      neuronal vulnerability clearly depends on other cellular characteristics such as
      morphology, connectivity, and other aspects of the neurochemical phenotype.

PMID- 9784284
TI  - The protein phosphatase inhibitor okadaic acid induces heat shock protein
      expression and neurodegeneration in rat hippocampus in vivo.
AB  - The tumor promoter okadaic acid is a potent and specific inhibitor of protein
      phosphatases 1 and 2A and therefore it is a useful tool for studying the
      participation of protein phosphorylation in cellular processes. Since it has been
      shown that in cultured neurons OKA behaves as a potent neurotoxin, in the present
      work we have administered different doses of this compound into the dorsal rat
      hippocampus, in order to assess its neurotoxicity in vivo. Cresyl violet staining
      of hippocampal sections revealed that as early as 3 h after injection of 300 ng
      OKA a notable neurodegeneration occurred in the CA1 subfield, the dentate gyrus,
      and the hilus, particularly in the former. Neuronal death was more evident at 24
      h and at this time the extent of damage was dose-dependent. The process of
      neuronal death was accompanied by a loss of the microtubule-associated protein
      MAP2, as assessed by immunocytochemistry. Moreover, OKA treatment resulted in a
      notable expression of the inducible heat shock protein 72 in the surviving
      neurons of the injected hippocampus and in the corresponding CA1 and hilus of the
      apparently normal contralateral hippocampus. The expression of the heat shock
      protein was partially prevented in the injected hippocampus and completely
      blocked in the contralateral CA1 region, by the systemic previous administration
      of the NMDA receptor antagonist MK-801. These results suggest that protein
      hyperphosphorylation due to inhibition of phosphatases in vivo induces neuronal
      stress and subsequent neurodegeneration.

PMID- 9784285
TI  - Purkinje cell transplants in Shaker mutant rats with hereditary Purkinje cell
      degeneration and ataxia.
AB  - Shaker mutant rats are characterized by the adult-onset degeneration of
      cerebellar anterior lobe Purkinje cells and temporally correlated development of
      ataxia and tremor. Normal E-13 Purkinje cells were transplanted into the anterior
      cerebellum in adult shaker mutant rats to study donor/host interactions in an
      animal with adult-onset heredodegeneration. Donor Purkinje cells from
      extraparenchymal transplant sites migrated radially into the host molecular layer
      and differentiated. Donor Purkinje cell dendrites expanded to fill the host
      molecular layer, spinous processes were apparent, and axonal projections into the
      host gray and white matter were observed. Donor Purkinje cells remaining in the
      extraparenchymal transplant sites differentiated if they were located relatively
      close to the host cerebellum. Donor Purkinje cells located intraparenchymally in
      the host white matter or granule cell layer survived, but were stunted in their
      development. The orthogonal movement of donor Purkinje cells away from transplant
      sites in the host cerebellum was spatially restricted. The findings from this
      study indicate that host cerebellar cortex with adult-onset heredodegeneration of
      Purkinje cells supports the survival and differentiation of transplanted normal
      embryonic Purkinje cells.

PMID- 9784286
TI  - Changes in the mitochondrial enzyme activity in striatal projection areas after
      unilateral excitotoxic striatal lesions: partial restoration by embryonic
      striatal transplants.
AB  - It is well established that the activity of cytochrome oxidase (CO), a
      mitochondrial enzyme, reflects the long-term, steady-state levels of neuronal
      activity. The present study investigated the long-term effects of unilateral
      striatal lesions induced by quinolinic acid on CO activity in primary striatal
      targets, including the globus pallidus (GP), entopeduncular nucleus (EP), and
      substantia nigra pars reticulata (SNR) and a secondary striatal projection area,
      such as subthalamic nucleus (STN), in rats. The activity of CO was determined by
      measuring staining intensity on brain sections processed for CO histochemistry.
      We also examined whether intrastriatal transplants of embryonic striatal tissue
      could affect the lesion-induced changes in the CO activity of those brain
      structures. Unilateral striatal lesions were found to lead to increases in the CO
      activity of the GP, EP, and SNR ipsilateral to the lesions. By contrast, the
      activity of the ipsilateral STN was decreased following striatal lesions,
      probably due to the increased inhibitory effect of the GP on the STN.
      Intrastriatal implantation of the lateral ganglionic eminence (LGN), but not the
      medial ganglionic eminence (MGE), reversed the lesion-induced changes in the CO
      activity of the GP and STN with concomitant attenuation of apomorphine-induced
      rotational asymmetry. The grafts failed to affect the activity of either the EP
      or SNR. The present results indicate that striatal lesions induce changes in the
      functional activity of basal ganglia nuclei and that the LGE grafts placed in the
      damaged striatum partly reverse the alterations in the functional state of the
      basal ganglia circuitry.

PMID- 9784287
TI  - In vivo electrochemical studies of dopamine clearance in subregions of rat
      nucleus accumbens: differential properties of the core and shell.
AB  - The dopamine (DA) uptake/clearance properties of the DA transporter (DAT) in the
      core and shell of the nucleus accumbens were measured using in vivo
      electrochemical recordings. Calibrated amounts of a DA solution were pressure
      ejected from a micropipette/electrode assembly placed in the core or shell of the
      nucleus accumbens in anesthetized male Fischer 344 rats. Initial studies in the
      two brain regions revealed that the core and shell have different DA clearance
      properties as measured by the extracellular DA signal amplitudes, clearance
      times, and clearance rates. Although the same number of picomoles of DA were
      applied, DA clearance signals recorded in shell had significantly greater
      amplitudes but faster clearance rates than those recorded in the core. Systemic
      administration of 20 mg/kg cocaine, a monoamine transporter inhibitor, greatly
      increased the signal amplitude from the locally applied DA in both the core and
      shell. Signal amplitudes were increased to a greater extent in the shell,
      compared with the core, after cocaine administration. However, cocaine affected
      the clearance time of DA only in the core and the DA clearance rate only in the
      shell. Taken together with previously reported data, these studies further
      support differential activity of the DAT in the core versus shell subregions of
      the nucleus accumbens. In addition, these data indicate that DATs are more
      sensitive to the effects of psychomotor stimulants, such as cocaine, in the shell
      of the nucleus accumbens.

PMID- 9784288
TI  - Task-dependent deficits during object release in Parkinson's disease.
AB  - The present study examined fingertip forces during the replacement and release of
      an instrumented object on a table in eight subjects with Parkinson's disease (PD)
      both off and on medication and eight age-matched control subjects. Subjects
      performed the task at (1) their preferred speeds and (2) as fast as possible.
      During performance of the task at preferred speed, the duration of object
      replacement, the rate, and duration of force decrease following table contact for
      PD subjects were similar to that observed in the control subjects and were
      unaffected by medication. In contrast, the rates were significantly lower and
      durations longer in the PD subjects when the task was performed as fast as
      possible irrespective of medication. A similar result was obtained when subjects
      were asked to release their pinch force from predefined force levels while the
      object was fixed to the table surface. These results emphasize the importance of
      considering task requirements in order to delineate the specific task parameters
      associated with the movement impairments in Parkinson's disease.

PMID- 9784289
TI  - High-resolution MRI of intact and transected rat spinal cord.
AB  - Spinal cord transection at midthoracic level leads to an immediate loss of
      hindlimb motor function as well as to a progressive degeneration of descending
      and ascending spinal cord pathways. Thoracic spinal cord in unlesioned control
      rats and in rats 2 to 6 months after complete midthoracic transection were imaged
      in vivo using an ultrahigh-field (4.7 T) magnetic resonance spectrometer. High
      resolution spin-echo and inversion-recovery pulse sequences were employed. In
      addition, the apparent diffusion coefficients (ADCs) in longitudinal and
      transverse directions of the spinal cord were determined. Anatomical MRI findings
      were confirmed in histological spinal cord tissue preparations. In healthy spinal
      cord, gray and white matter were easily discerned in proton density-weighted
      images. An infield resolution of max. 76 micrometers per pixel was achieved. In
      animals with chronic spinal cord transection changes in gray-white matter
      structure and contrast were observed toward the cut end. The spinal cord stumps
      showed a tapering off. This coincided with changes in the longitudinal/transverse
      ADC ratio. Fluid-filled cysts were found in most cases at the distal end of the
      rostral stump. The gap between the stumps contained richly vascularized scar
      tissue. Additional pathologic changes included intramedullary microcysts,
      vertebral dislocations, and in one animal compression of the spinal cord. In
      conclusion, MRI was found to be a useful method for in vivo investigation of
      anatomical and physiological changes following spinal cord transection and to
      estimate the degree of neural degeneration. In addition, MRI allows the
      description of the accurate extension of fluid spaces (e.g., cysts) and of water
      diffusion characteristics which cannot be achieved by other means in vivo.

PMID- 9784290
TI  - Regulation of semaphorin III/collapsin-1 gene expression during peripheral nerve
      regeneration.
AB  - The competence of neurons to regenerate depends on their ability to initiate a
      program of gene expression supporting growth and on the growth-permissive
      properties of glial cells in the distal stump of the injured nerve. Most studies
      on intrinsic molecular mechanisms governing peripheral nerve regeneration have
      focussed on the lesion-induced expression of proteins promoting growth cone
      motility, neurite extension, and adhesion. However, little is known about the
      expression of intrinsic chemorepulsive proteins and their receptors, after
      peripheral nerve injury and during nerve regeneration. Here we report the effect
      of peripheral nerve injury on the expression of the genes encoding sema III/coll
      1 and its receptor neuropilin-1, which are known to be expressed in adult sensory
      and/or motor neurons. We have shown that peripheral nerve crush or transection
      results in a decline in sema III/coll-1 mRNA expression in injured spinal and
      facial motor neurons. This decline was paralleled by an induction in the
      expression of the growth-associated protein B-50/GAP-43. As sema III/coll-1
      returned to normal levels following nerve crush, B-50/GAP-43 returned to precrush
      levels. Thus, the decline in sema III/coll-1 mRNA coincided with sensory and
      motor neuron regeneration. A sustained decline in sema III/coll-1 mRNA expression
      was found when regeneration was blocked by nerve transection and ligation. No
      changes were observed in neuropilin-1 mRNA levels after injury to sensory and
      motor neurons, suggesting that regenerating peripheral neurons continue to be
      sensitive to sema III/coll-1. Therefore we propose that a decreased expression of
      sema III/coll-1, one of the major ligands for neuropilin-1, during peripheral
      nerve regeneration is an important molecular event that is part of the adaptive
      response related to the success of regenerative neurite outgrowth occurring
      following peripheral nerve injury.

PMID- 9784291
TI  - Weak ELF magnetic field effects on hippocampal rhythmic slow activity.
AB  - Several investigations have revealed that electrical activity within the central
      nervous system (CNS) can be affected by exposure to weak extremely-low-frequency
      (ELF) magnetic fields. Many of these studies have implicated CNS structures
      exhibiting endogenous oscillation and synchrony as optimal sites for field
      coupling. A particularly well characterized structure in this regard is the rat
      hippocampus. Under urethane anesthesia, synchronous bursting among hippocampal
      pyramidal neurons produces a large-amplitude quasi-sinusoidal field potential
      oscillation, termed "rhythmic slow activity" (RSA) or "theta." Using this in vivo
      model, we investigated the effect of exposure to an externally applied sinusoidal
      magnetic field (16.0 Hz; 28.9 microT(rms)) on RSA. During a 60-min exposure
      interval, the probability of RSA decaying to a less coherent mode of oscillation,
      termed "large irregular-amplitude activity" (LIA), was increased significantly.
      Moreover, this instability persisted for up to 90 min postexposure. These results
      are consistent with the hypothesis that endogenous CNS oscillators are uniquely
      susceptible to field-mediated perturbation and suggest that the sensitivity of
      these networks to such fields may be far greater than had previously been
      assumed. This sensitivity may reflect nonlinearities inherent to these networks
      which permit amplification of endogenous fields mediating the initiation and
      propagation of neuronal synchrony.

PMID- 9784292
TI  - Differential toxicity of protease inhibitors in cultures of cerebellar granule
      neurons.
AB  - Involvement of proteases has been postulated in several neurodegenerative
      processes. Accordingly, protease inhibition has been proposed as a potential
      therapeutic tool to limit damage in some neuropathological states. The timed turn
      over of proteins is, however, an essential biochemical process and its prolonged
      block may be dangerous to the cell. We report here data on toxicity consequent to
      24-h exposure of cerebellar granule neurons in culture to inhibitors of different
      classes of proteases. Inhibition of calpains (calcium-activated cysteine
      proteases) resulted in dose-dependent neuronal death which largely occurred
      through apoptotic process. Leupeptin, an inhibitor acting on a broad spectrum of
      cellular serine proteases, was less toxic but resulted in definite morphological
      alteration of the cells. On the contrary, inhibitors of caspases, proteases
      belonging to the ICE (interleukin 1-beta converting enzyme) family, did not
      apparently damage granule neurons upon exposure for 24 h to high concentrations
      (up to 200 microM) of two inhibitors specific for ICE (Ac-YAVD-CHO) and CPP-32
      (Ac-DEVD-CHO), respectively. These results suggest that inhibition of proteases
      that are activated by stressful stimuli but are not essential for the normal
      functioning of healthy cells, as it is likely the case for caspases, may not be
      harmful to neurons. Instead, the potential risks and side effects of prolonged
      inhibition of proteases such as calpains, that regulate the disposal and the turn
      over of key cellular proteins, should be carefully tested in the assessment of
      possible neuroprotective roles.

PMID- 9784294
TI  - Involvement of precerebellar nuclei in Pick's disease.
AB  - Pick's disease is a progressive degenerative disorder of the human brain which
      involves not only numerous areas of the cerebral cortex but also a characteristic
      set of subcortical nuclei. The disorder is associated with the formation of
      abnormal and hyperphosphorylated tau protein, which occurs in only a few
      susceptible neuronal types and leads to major cytoskeletal alterations.
      Preferentially affected by the destructive process are small nerve cells of both
      cortical areas and subcortical nuclei. Immunoreactions for abnormally
      phosphorylated tau protein permit identification of the alterations in their
      entirety. In an initial step in their development, patches of a nonargyrophilic
      material appear, irregularly filling both the somata and neurites of afflicted
      cells. The abnormal material is then partially converted into condensed spindle
      shaped or spherical structures, which gradually become significantly
      argyrophilic. Globose argyrophilic Pick bodies eventually appear within the
      somata, and small Pick neurites of variable sizes and shapes develop in varicose
      expansions of the dendritic processes. Silver staining reveals only a fraction of
      the abnormal material and is adequate only for diagnostic purposes, while
      immunostaining of the abnormal tau protein discloses the complete
      neuropathological picture. The present study points to a conspicuous affliction
      of specific precerebellar nuclei in Pick's disease. Immunoreactive punctae,
      probably corresponding to terminal synaptic boutons of afferent fibers, appear at
      sites in the inferior olive receiving intense input from the cerebral cortex. The
      brunt of the changes, however, are borne by the pontine gray, the arcuate
      nucleus, the pontobulbar body, and the paramedian reticular nucleus. Altered
      areas show immunoreactive punctae and an abundance of small immunoreactive nerve
      cells partially containing Pick bodies and Pick neurites. Again, a feature common
      to all the affected nuclei is that they receive major input from the cerebral
      cortex, while other precerebellar nuclei with preponderant input from the spinal
      cord and/or other noncortical sources remain unscathed or exhibit only sparse
      involvement. The lesional pattern which develops in specific precerebellar nuclei
      is interpreted to be a partial reflection of the cortical involvement of Pick's
      disease.

PMID- 9784295
TI  - Fifth annual conference of the american society for neural transplantation 

PMID- 9784293
TI  - Mechanisms of uptake of gallium by human neuroblastoma cells and effects of
      gallium and aluminum on cell growth, lysosomal protease, and choline acetyl
      transferase activity.
AB  - We have studied the uptake and removal of gallium, used as an analogue of
      aluminum, and the effects of aluminum itself on cultured human neuroblastoma
      cells treated with soluble metal complexes. The prohibitively high cost of
      measurement of the only available radioisotope of aluminum (26Al) precluded its
      usage, and so we considered that gallium, which is chemically extremely similar,
      would be the most suitable model. Gallium has been used thus in a number of
      previous biological studies and has been found to behave like aluminum in many
      respects. We have previously shown that Al-EDTA treatment results in uptake of
      aluminum and expression of hyperphosphorylated tau, a key component of
      Alzheimer's disease paired helical filaments. Here we demonstrate that gallium
      uptake can occur by two separate methods, both leading to physiologically
      relevant intracellular metal concentrations. Uptake from medium containing bovine
      transferrin occurred mainly by pinocytosis, but in the presence of human
      transferrin (hTf), uptake by transferrin-mediated endocytosis occurred also,
      despite a very low level of hTf saturation, indicating that Tf-mediated uptake is
      a very effective method of Ga internalization. The intracellular gallium is
      relatively stable, though partially removable by (1 mM) EDTA, desferrioxamine, or
      1,2-dimethyl-3-hydroxypyrid-4-one. Aluminum and gallium treatment were found to
      increase the overall activity of lysosomal proteases, enzymes implicated in
      amyloid precursor protein cleavage. No effects were detected on choline acetyl
      transferase activity, cell growth, or tritiated thymidine incorporation or on the
      structure of the cells, as judged by light or electron microscopy.

PMID- 9784296
TI  - Influence of calcitonin on serum calcium levels of intact or hypophysectomized
      freshwater catfish Heteropneustes fossilis.
AB  - Serum calcium levels were markedly reduced in male freshwater catfish
      Heteropneustes fossilis following hypophysectomy. The administration of salmon
      calcitonin to intact fish had no effect on serum calcium level, whereas the same
      treatment to hypophysectomized fish induced hypocalcemia.

PMID- 9784297
TI  - Amino acid sequence diversity of pancreatic polypeptide among the amphibia.
AB  - It has been suggested that the amino acid sequence of pancreatic polypeptide (PP)
      may provide a useful molecular marker with which to study evolutionary
      relationships between tetrapods but few PP sequences from amphibia are available
      to test this hypothesis. PPs have been purified from the pancreata of five
      species belonging to the different orders of amphibians. Their amino acid
      sequences were established as: APSEPEHPGD10 NASPDELAKY20 YSDLWQYITF30 VGRPRY for
      the lesser siren, Siren intermedia (Caudata); GPTEPIHPGK10 DATPEELTKY20
      YSDLYDYITL30 VGRSRW for the caecilian, Typhlonectes natans (Gymnophiona); and
      TPSEPQHPGD10 QASPEQLAQY20 YSDLWQYITF30 VTRPRF for the cane toad, Bufo marinus
      (Anura). The structure of Rana sylvatica PP is the same as that of Rana
      catesbeiana PP whereas PP from the green frog Rana ridibunda contains one
      substitution (His6 --> Gln). The data provide further support for the conclusion
      that the amino acid sequence of PP has been poorly conserved during evolution
      with only 17 residues invariant among the eight species of amphibia yet studied
      and only 8 residues (Pro5, Pro8, Gly9, Ala12, Leu24, Tyr27, Arg33, and Arg35)
      invariant among all tetrapods. A maximum parsimony analysis based upon the amino
      acid sequence of PP and using the sequence of frog PYY as outgroup to polarize
      the in-group taxa generates a consensus phylogenetic tree in which the Amniota
      and Amphibia form two distinct clades. However, such a tree does not permit valid
      conclusions to be drawn regarding branching order within the Amphibia.

PMID- 9784298
TI  - Isolation of functional glucagon islets of Langerhans from the chicken pancreas.
AB  - Two types of islets of Langerhans are present in the avian endocrine pancreas:
      glucagon islets (A-islets) and insulin islets (B-islets). Islets from the chicken
      pancreas were isolated by ductal injection of collagenase, enzymatic digestion,
      atraumatic dispersion of the digests at an appropriate time, and nylon mesh
      filtrations. A- and B-islets were identified by immunohistochemistry and
      radioimmunological quantification of insulin and glucagon. Dithizone-positive
      islets proved to be mostly of the A-type by immunostaining, and
      radioimmunological measurements: islets from the cranial half of the body of the
      pancreas were almost pure (95%) glucagon islets (0.454 +/- 0.027 pmol glucagon
      and 0.023 +/- 0.005 pmol insulin per islet). Increasing the glucose concentration
      in the incubation medium from 14 to 42 mM decreased glucagon release,
      demonstrating that the alpha-cells maintained their glucose sensitivity after
      isolation.

PMID- 9784299
TI  - Gonadotrophin-releasing hormone agonist stimulates milt fluidity and plasma
      concentrations of 17,20beta-dihydroxylated and 5beta-reduced, 3alpha-hydroxylated
      C21 steroids in male plaice (Pleuronectes platessa).
AB  - Spermiating male plaice were caught in the North Sea and acclimatised to
      laboratory conditions. In two experiments, males were injected intramuscularly
      with either microspheres or pellets containing gonadotrophin-releasing hormone
      agonist (GnRHa). Blood was sampled at 2- to 5-day intervals. Individual blood
      plasma specimens were assayed for testosterone, 5beta-reduced, 3alpha-hydroxy
      ("5beta,3alpha") steroids and sulphated 17, 20beta-dihydroxy ("17,20beta")
      steroids. Pooled plasma samples were also assayed for free and sulphated 17,
      20beta-dihydroxy-4-pregnen-3-one, free 11-ketotestosterone, and glucuronidated
      testosterone and 11-ketotestosterone. Plasma concentrations of all steroids were
      significantly elevated by GnRHa from 2 to 5 days onwards following treatment. The
      most marked changes occurred in the concentrations of the sulphated 17,20beta
      steroids, which comprised approximately equal amounts of 5beta-pregnane
      3alpha,17,20beta-triol 20-sulphate (3alpha,17, 20beta-P-5beta-S) and 5beta
      pregnane-3beta,17,20beta-triol 20-sulphate, rising from ca. 1 to 30-80 ng/ml in
      the first and from ca. 8 to 80 ng/ml in the second experiment. Concentrations of
      5beta, 3alpha steroids matched those of 17,20beta steroids in one experiment.
      However, in the other experiment, the two RIAs yielded highly disparate results
      in about 50% of the fish (including males in the control group). The plasma of
      these fish contained excessive amounts of 5beta,3alpha-immunoreactive material
      between 10 and 25 days. This material was identified as 3alpha,17, 21-trihydroxy
      5beta-pregnan-20-one 21-sulphate (a metabolite of 11-deoxycortisol). All previous
      studies have indicated that when plasma concentrations of this steroid are high,
      so are those of 3alpha,17,20beta-P-5beta-S. This is the first indication that
      these steroids are regulated independently. In a third experiment, milt fluidity
      and production were assessed at 10, 15, and 25 days following GnRHa implantation.
      Milt volume and fluidity were significantly enhanced by the GnRHa treatment.

PMID- 9784300
TI  - Use of a GnRH agonist to suppress testosterone in wild male Hawaiian monk seals
      (Monachus schauinslandi).
AB  - A gonadotropin-releasing hormone (GnRH) agonist, d-Trp6-LHRH, was evaluated for
      its effectiveness in reducing circulating testosterone concentrations in wild
      Hawaiian monk seals (Monachus schauinslandi). Twenty-eight adult male seals were
      randomly divided into three groups: 10 were captured and treated with 7.5 mg of
      the GnRH agonist, 9 were captured but did not receive the agonist, and 9 were
      captured near the end of the study to serve as handling controls. Blood samples
      were taken from all 28 seals. From 14 to 58 days after initial capture, 8 of the
      treated seals and 8 of the untreated seals were recaptured and a second sample of
      blood was taken. For comparison, blood was also collected from 4 captive adult
      male seals during the same months as the field study. In the treated group, the
      agonist induced a significant decline in mean circulating testosterone
      concentrations, from 1.01 ng/ml (first sample) to 0.21 ng/ml (second sample,
      taken approximately 38 days later). In the untreated group, mean testosterone
      concentrations of the first and second samples were statistically
      indistinguishable (1.11 vs 1.16 ng/ml). The mean concentration of the untreated
      group (second sample) was also indistinguishable from the mean concentration of
      seals in the control group (1.16 vs 0.82 ng/ml). Also, mean testosterone
      concentration in the initial samples from the four captive seals was not
      statistically different from that of untreated wild seals (1.38 vs 1.11 ng/ml).
      These results suggest that (1) the GnRH agonist suppresses the production of
      testosterone in wild adult male Hawaiian monk seals, (2) a single handling of
      adult male seals does not affect their testosterone levels, and (3) testosterone
      concentrations in captive male seals appear to be consistent with concentrations
      in wild seals. Further evaluation of this GnRH agonist is necessary before it is
      used in the management of this endangered species, but these results suggest it
      may be a useful tool for reducing mortality of monk seals from adult male
      aggression related to reproduction and mating behavior.

PMID- 9784302
TI  - Responses of frog skin, Rana pipiens, calcium ion transport to parathyroid
      hormone, calcitonin, and vitamin D3.
AB  - The responses of cutaneous Ca2+ transport to parathyroid hormone, calcitonin, and
      vitamin D3 were evaluated in intact Rana pipiens and isolated skins from this
      species. Parathyroid hormone (12 pmol g-1) stimulated Ca2+ influx in intact frogs
      but not in isolated skin (10-100 pmol ml-1) unless the frogs had been pretreated
      with vitamin D3 injections (100-300 microgram day-1) for 3 days prior to
      isolating the skins for flux measurements. Pretreatment of intact frogs with
      vitamin D3 for 3 days (100 microgram day-1) also resulted in greater responses to
      PTH (6-12 pmol g-1). Vitamin D3 (most likely after conversion to 1,25(OH)2D3) had
      a direct stimulatory effect on Ca2+ transport in isolated skins after three daily
      doses of 500 microgram of D3. Calcitonin also stimulated Ca2+ influx in both
      intact frogs (24 pmol g-1) and isolated skins (25-100 pmol ml-1). We conclude
      that parathyroid hormone, facilitated by vitamin D, stimulates Ca2+ influx in the
      skin of R. pipiens. We also conclude that calcitonin is stimulatory for cutaneous
      Ca2+ influx in this species.

PMID- 9784301
TI  - Somatostatin binding to hepatocytes isolated from rainbow trout, Oncorhynchus
      mykiss, is modulated by insulin and glucagon.
AB  - Previously we reported somatostatin-14 (SS-14) binding in the liver of rainbow
      trout and that fasting enhanced SS-14-binding capacity. In this study, we used
      hepatocytes isolated from rainbow trout to study aspects of SS-14 processing and
      to evaluate the basis of fasting-associated changes in SS-14 binding. Hepatocytes
      specifically bound 5-8% of the total 125I-SS-14 added. Scatchard analysis
      revealed the existence of two classes of binding sites. The high-affinity site
      had a dissociation constant (Kd) of 23.6 +/- 1.1 nM and a binding capacity (Bmax)
      of 3459 +/- 134 receptors/cell. The low-affinity site had a Kd of 764 +/- 27 nM
      and a Bmax of 17,432 +/- 345 receptors/cell. 125I-SS-14 dissociation was hastened
      by the presence of 10(-6) M SS-14 . The internalization of 125I-SS-14 was time
      dependent; preincubation of hepatocytes with 10(-6) M SS-14 reduced
      internalization of 125I-SS-14. The number of high-affinity binding sites was also
      reduced by 10(-6) M SS-14. Because plasma levels of insulin (INS) decline
      relative to those of glucagon (GLU) during fasting of trout, we also investigated
      the effects of these hormones on SS-14 binding. The number of high-affinity SS-14
      binding sites was reduced by 10(-6) M INS and was increased by 10(-6) M and 10(
      8) M GLU. These results indicated that SS-14 regulates aspects of SS-14 binding
      and processing and suggests that INS and GLU play a role in fasting-associated
      changes in SS-14 binding.

PMID- 9784303
TI  - The effect of food intake from 2 to 24 weeks of age on LHRH-I content in the
      median eminence and gonadotrophin levels in pituitary and plasma in female
      broiler breeder chickens.
AB  - The present study describes the effect of long-term food restriction on
      hypothalamopituitary function in the broiler breeder hen during the period prior
      to sexual maturity. From 1 week of age onward, chickens were divided into 3
      groups: one group received food ad libitum (Ad lib); a second group was fed a
      restricted quantity of food (Res); and a third group was restricted to obtain an
      intermediate body weight (Int) in between groups one and two. The effects of
      these feeding regimes on hypothalamopituitary function were assessed by measuring
      the amounts of cLHRH-I stored in the median eminence (ME) and the pituitary
      content and plasma levels of gonadotrophins. The Res group had significantly
      lower levels of cLHRH-I in the ME compared to the Ad lib animals. In all groups,
      there was a major increase in cLHRH-I in the median eminence about 3 weeks before
      onset of lay. The age of first oviposition was delayed by 2 and 6 weeks in the
      Int and Res groups, respectively, compared to the Ad lib animals, indicating that
      body weight gain patterns are not directly related to the appearance of the first
      egg. The attainment of sexual maturity may be associated with a threshold value
      of cLHRH-I stored in the ME in the Ad lib and Int birds. The pituitary LH and FSH
      contents (after week 16) were positively related to the amount of cLHRH-I in the
      ME. Plasma FSH concentrations in Ad lib and Int chickens peaked about 3 weeks
      before the first oviposition and this prepubertal peak was associated with
      increased pituitary FSH and ME cLHRH-I. There were however no relationships
      between plasma LH concentrations and pituitary LH content and between plasma LH
      and cLHRH-I amounts in the ME. The present study demonstrates that the delayed
      sexual maturation, caused by a chronic food restriction, may be associated with
      (1) delayed ovarian and oviductal growth, (2) decreased cLHRH-I storage in the
      ME, and (3) lower levels of LH and FSH in the pituitary. These hormones were
      however not directly related to levels of food restriction.

PMID- 9784304
TI  - Native urotensins influence cortisol secretion and plasma cortisol concentration
      in the euryhaline flounder, platichthys flesus.
AB  - Adrenocorticotrophic hormone (ACTH) and flounder urotensins I and II (UI and UII)
      stimulate cortisol secretion of isolated interrenal/head kidney preparations of
      seawater (SW)-adapted flounder. UI and UII at concentrations of 10(-6) and 10(-7)
      M, respectively, increased cortisol secretion when acting on SW-derived
      interrenal but did not affect cortisol secretion in tissue derived from
      freshwater (FW) fish. Combined UI and UII had no synergistic or additive
      steroidogenic action, but either 10(-7) M UI or 10(-7) M UII in combination with
      ACTH produced a very marked, additive, or synergistic steroidogenic response,
      most apparent on interrenal derived from FW fish. These results suggest that
      urotensins enhance the steroidogenic action of ACTH in flounder. In all cases,
      significant steroidogenesis was apparent within 1 h postperifusion of ligands. In
      SW-adapted flounder intraarterial infusion of UII in vivo caused a concentration
      dependent increase in plasma cortisol concentration within 1 h after infusion,
      while after 5 x 10(-6) M UI infusion a similar trend was evident but this did not
      achieve statistical significance. The data suggest that the caudal neurosecretory
      system may control interrenal cortisol secretion, to modulate cortisol secretion
      independently of the hypophysial axis, perhaps in response to specific stress
      induced or osmoregulatory challenge.

PMID- 9784305
TI  - Melanocortin receptor genes in the chicken--tissue distributions.
AB  - Two receptor genes belonging to the melanocortin receptor (MC-R) family were
      isolated in the chicken, the CMC4 and CMC5, each of which is a chicken homologue
      of the mammalian MC4-R and MC5-R, respectively. The CMC4 encodes a 331 amino acid
      protein, sharing 86. 4-88.1% identity with mammalian analogs, and the CMC5
      encodes a 325 amino acid protein, which is 72.3-79.1% identical to mammalian
      counterparts. Both genes contain no intron in their coding regions and exist in
      the chicken genome as single copy genes. Reverse transcription-PCR analysis
      revealed that the CMC4 mRNA is expressed in a wide variety of peripheral tissues,
      including the adrenal, gonads, spleen, and adipose tissues, as well as in the
      brain, where mammalian counterparts are exclusively expressed in the brain,
      indicating that the regulation of MC4-R gene expression differs between mammals
      and chickens. The CMC5 mRNA, on the other hand, is expressed in the liver,
      gonads, adrenal, kidney, brain, and adipose tissues as well as in the uropygial
      gland. These findings raise the possibility that melanocortins affect a variety
      of functions both in the brain and in the peripheral tissues of the chicken.

PMID- 9784307
TI  - Ontogeny of prolactin-secreting cells during chick embryonic development: effect
      of vasoactive intestinal peptide.
AB  - It was previously reported that prolactin (PRL)-containing cells differentiate by
      days 15 to 19 of embryonic development and that vasoactive intestinal peptide
      (VIP) increased plasma PRL concentrations and pituitary PRL protein and mRNA
      levels in vivo. In the present study, anterior pituitaries derived from day 15,
      16, 17, 18, and 19 embryos were subjected to reverse hemolytic plaque assays
      (RHPA) for chicken PRL to determine the ontogeny of lactotrophs. We found that
      PRL secreting cells were first consistently detected on day 17 of embryonic
      development, indicating that lactotroph differentiation during normal development
      occurs by this age. However, extended treatment in the RHPA with VIP exposed
      lactotrophs as early as day 15, suggesting that a lactotroph precursor population
      was present earlier. Next, primary cultures of embryonic anterior pituitary cells
      from day 12, 13, 14, 15, 16, and 17 embryos were incubated for 0, 2, or 4 days in
      serum-free medium or medium supplemented with 10 nM VIP. After the culture
      periods, cells were subjected to RHPAs for chicken PRL. PRL-secreting cells
      differentiated spontaneously by 2 days in culture for day 15 and 16 cells and by
      4 days in culture for all embryonic ages tested, except day 17. Culturing with
      VIP for 2 days did not increase PRL-secreting cells at any embryonic age tested,
      whereas VIP treatment for 4 days increased lactotroph numbers at all ages except
      day 12. Cells from days 15, 16, and 17 were responsive to VIP in the RHPA after 2
      days in untreated cultures, but after 4 days only day 17 cells continued to
      respond to VIP in the RHPA. Treatment with VIP in culture for 4 days maintained
      VIP responsiveness in the RHPA for cells derived from embryos as early as day 14.
      We conclude that lactotroph differentiation during normal chicken development
      occurs by embryonic day 17. Moreover, our results indicate that responsiveness to
      VIP is an early event in PRL cell development and that lactotroph differentiation
      may be stimulated in vitro by VIP as early as embryonic day 13.

PMID- 9784306
TI  - Angiotensin II and angiotensin-converting enzyme as candidate compounds
      modulating the effects of testis ecdysiotropin in testes of the gypsy moth,
      Lymantria dispar1.
AB  - Lymantria dispar testes synthesize immunodetectable ecdysteroid in vitro in
      response to the brain peptide, testis ecdysiotropin (TE), acting primarily via a
      cascade involving Gi protein, diacyl glycerol, and phosphokinase C. However, a
      component of TE activation also involves the opposite cascade, Gs protein, cAMP,
      and phosphokinase A. Excess cAMP inhibits the action of TE, acting as a feedback
      modulator. Here, we show that bovine angiotensin II (AII) and bovine angiotensin
      converting enzyme (ACE) act like cAMP, inducing synthesis of immunodetectable
      ecdysteroid by pupal testes in vitro, but are antagonistic to coincubated TE. In
      addition, an insect ACE antibody clearly stains the spermatogenic cells through
      all stages of development, as well as testis sheath tissue where ecdysteroid is
      synthesized. AII induces synthesis of cAMP by pupal testes in vitro. Therefore,
      insect homologs of mammalian AII and ACE are good candidates for the peptides
      responsible for the cAMP cascade and as modulators of TE action in lepidopteran
      testes. Saralasin, an analog of AII that blocks angiotensin receptors in mammals,
      behaved like AII in inducing ecdysteroid secretion with ecdysteroidogenic effects
      additive to either angiotensin or ACE. Therefore, the receptors for the insect
      form of angiotensin on lepidopteran testis cells are probably different from
      those in mammals. Saralasin also inhibited ecdysteroid synthesis when combined
      with TE, as did AII.

PMID- 9784308
TI  - Gastrin and cholecystokinin of the bullfrog, Rana catesbeiana, have distinct
      effects on gallbladder motility and gastric acid secretion in vitro.
AB  - Many regulatory peptides form families with at least two homologous members. For
      several such families the divergence of the individual members from a common
      ancestor can be dated to early in vertebrate history. Cholecystokinin (CCK) and
      gastrin were originally identified in mammals. Recently, two distinct members of
      the CCK/gastrin family were identified in the bullfrog (Rana catesbeiana), termed
      CCK and gastrin. Frog gastrin is very similar to CCK in the region defining
      biological activity. To evaluate whether the two endogenous peptides have
      distinct properties, their effects were studied in typical target organs. While
      porcine gallbladder responded equally to frog gastrin-8 and CCK-8, EC50 values
      for stimulation of bullfrog gallbladder contractions were 490 nM (gastrin) and 69
      nM (CCK). In contrast, gastrin appeared to be a more potent stimulant of acid
      secretion than CCK; the estimated EC50 values are 3.1 and 17.2 nM, respectively.
      Furthermore, gastrin had a significantly higher efficacy than CCK-8s. Thus, in
      spite of their close structural resemblance, there are clear differences between
      the two endogenous peptides in their action on gallbladder and gastric mucosa. It
      is concluded that there are distinct gastrin and CCK functions already at the
      amphibian level of evolution.

PMID- 9784309
TI  - Seasonal variations in the function of the endocrine pancreas in Psammomys
      obesus.
AB  - The aim of this work was to determine whether Psammomys obesus living in its
      natural habitat displays variation in the function of the endocrine pancreas.
      Live animals were collected regularly through the year by strip sampling. Plasma
      glucose varied during the year. Glucose levels were higher in periods I and III
      (autumn and spring) than in periods II and IV (winter and summer). Pancreatic
      insulin contents were higher in periods I and II than in periods III and IV.
      Plasma insulin also varied with the season in synchrony with glucose variations
      except during period IV, in which elevated levels of insulin were associated with
      low levels of glucose. The high insulin levels observed in period IV were
      resistant to the effects of food restriction in that period and were probably
      related to the presence of the greater levels of insulin in period III (spring).
      The dry season (period IV) corresponding to the period of restricted diet appears
      necessary to restore elevated levels of insulin to baseline. Morphometric
      quantitation of the insulin, glucagon, and somatostatin positive islet cells did
      not reveal seasonal variation. However, the volume density of A and D cells in P.
      obesus reached high values of 32 and 15%, respectively. The volume density of
      insulin cells amounted to about 53%. It is concluded that P. obesus living in its
      natural habitat is a nondiabetic healthy gerbil adapted to desert subsistence by
      endocrine feedback, imposed by the seasonal variation in food availability.

PMID- 9784310
TI  - Regulation of gill cytosolic corticosteroid receptors in juvenile Atlantic
      salmon: interaction effects of growth hormone with prolactin and
      triiodothyronine.
AB  - The potential effects of growth hormone (GH), prolactin (Prl), and
      triiodothyronine (T3) on gill Na+,K+-ATPase activity and corticosteroid receptor
      (CR) concentration (Bmax) and dissociation constant (Kd) were examined in
      juvenile Atlantic salmon (Salmo salar). Compared to controls, fish injected with
      GH (ovine, 5.0 microgram g-1) had significantly greater gill Na+,K+-ATPase
      activity after 7 and 14 days. Gill CR Bmax and Kd were significantly elevated on
      day 7, but not day 14. T3 also significantly increased CR Bmax. The effect of GH
      on CR Bmax was also additive with T3 (5.0 microgram g-1) treatment. There was a
      synergistic effect on CR Bmax when purified coho salmon GH (csGH, 0.1 microgram g
      1) was injected in combination with T3 (1.6 microgram g-1). Prl (ovine, 5.0
      microgram g-1; purified coho salmon, 0.1 microgram g-1) did not significantly
      alter gill CR Bmax. Although Prl limited the increase in CR Bmax by GH, the
      effect was not signicant. T3 and Prl did not have an effect on Kd. GH
      significantly increased gill Na+,K+-ATPase activity, T3 administration did not
      have a significant effect, and Prl-treated fish had significantly lower gill
      Na+,K+-ATPase activity. The results indicate that T3 acts additively with GH,
      while Prl has no effect in regulating CR Bmax. An increase in cytosolic CR by GH
      and T3, but not Prl, may regulate gill responsiveness to cortisol and be an
      important mechanism in the endocrine control of physiological changes during the
      parr-smolt transformation.

PMID- 9784311
TI  - DNA content and S-phase fraction in epithelial ovarian cancer: what information
      do they really add?

PMID- 9784312
TI  - Prognostic significance of DNA content and S-phase fraction in epithelial ovarian
      carcinomas analyzed by image cytometry.
AB  - The objective of this study was to evaluate the prognostic significance of DNA
      ploidy and S-phase fraction (SPF) in epithelial ovarian carcinomas analyzed by
      image cytometry. Frozen tissue of 103 epithelial ovarian carcinomas was analyzed
      for DNA ploidy and SPF with a Cell Analysis System Image Analyser (CAS 200,
      Becton-Dickinson) and correlations with clinical and histomorphologic factors and
      time to progression and overall survival were evaluated by univariate and
      multivariable analysis. Fifty-four percent of the ovarian carcinomas were found
      to be diploid, 38% aneuploid, and 8% tetraploid. The S-phase fraction was low
      (<5%) in 27%, intermediate (5-14.5%) in 47%, and high (>/=14.5%) in 26% of the
      patients. By univariate analysis overall survival and time to progression were
      significantly correlated with the S-phase fraction (P = 0.003 and P = 0.003), but
      not with DNA ploidy (P = 0. 31 and P = 0.51). A DNA index > 1.4 was correlated
      with poor outcome but the result did not achieve formal statistical significance
      (P = 0.08 and P = 0.12). A high SPF was a strong predictor of early recurrence,
      while a low SPF identified patients with a favorable long-term outcome. Other
      significant predictors of survival were FIGO stage, grade of differentiation,
      presence of distant metastasis, residual tumor, lymph node metastasis, and
      patient age. In multivariable statistical analysis only FIGO stage, histologic
      grade, and residual tumor after surgery were independent predictors of overall
      survival and time to progression.

PMID- 9784313
TI  - DNA content of ovarian immature teratomas and malignant germ cell tumors.
AB  - OBJECTIVE: Ovarian germ cell tumors (GCT) show greater histologic and biologic
      heterogeneity than their testicular counterparts and remain poorly understood.
      Ploidy analysis was performed on ovarian GCT registered on Pediatric Oncology
      Group germ cell tumor protocols 9048 and 9049 to distinguish biologically
      distinct subsets of immature teratomas and malignant ovarian germ cell tumors.
      METHODS: Tumors from 22 patients (mean age 12 years) were analyzed and classified
      according to the submitting diagnosis; when pure samples of different histologic
      subtypes within a single tumor were possible, these were analyzed separately.
      Archival tissue was disaggregated and Feulgen stained; DNA index (DI) was
      determined by static image analysis utilizing internal normal cells as diploid
      controls. RESULTS: 26 histologic subtypes from 22 patients were analyzed. The
      tumors of 18 patients were composed of a single histologic subtype according to
      the submitting institution, including 6 dysgerminomas, 8 immature teratomas (IT),
      and 4 endodermal sinus tumors (EST). Two tumors contained both IT and EST
      components that were separately analyzed. Two tumors were classified as mixed
      germ cell tumors; 1 showed multiple intermingling subtypes unable to be
      separately analyzed and the second showed three histologic subtypes separately
      analyzed (IT, EST, embryonal carcinoma). From a total of 15 malignant histologic
      GCT subtypes in 14 patients, all but 2 demonstrated a DI of 1.4-2.4 (mean 1.85).
      Two diploid malignant GCT (1 EST, 1 dysgerminoma) were both associated with
      gonadoblastoma. Overall, 11 IT subtypes were analyzed and 9 were diploid (2 grade
      1, 5 grade 2, and 2 grade 3). Two tumors originally submitted and classified as
      pure IT (grades 2 and 3) were aneuploid with a dominant diploid and a secondary
      aneuploid peak (both DI 1.7). On central review, both of these tumors
      demonstrated the presence of subtle patterns of EST that were unrecognized by the
      submitting institution and were much too small for separate analysis. Analysis of
      the 3 patients containing sufficient IT and EST to be separately analyzed all
      showed a diploid IT component and an aneuploid EST component. CONCLUSIONS:
      Analysis of ploidy data suggests that polyploidization is a consistent finding in
      malignant ovarian GCT arising in normal patients, similar to the data for adult
      testicular GCT. Immature teratomas in this pediatric population, however, are
      most commonly diploid, regardless of grade. The development of EST within an IT
      is associated with the development of an aneuploid clone. Therefore, the finding
      of such a clone in an IT may be of diagnostic utility, as EST may be difficult to
      recognize. Last, the development of a malignant GCT in patients with gonadal
      dysgenesis may be pathogenetically different from those arising in normal
      patients, in that polyploidization is not required.

PMID- 9784314
TI  - Laparoscopic para-aortic and pelvic lymphadenectomy: experience with 150 patients
      and review of the literature.
AB  - OBJECTIVE: The clinical usefulness of laparoscopic pelvic and para-aortic
      lymphadenectomy for staging and therapy of gynecological cancer was analyzed
      prospectively. METHOD: Laparoscopic para-aortic and pelvic lymphadenectomy was
      performed in 150 patients with cervical (n = 96), endometrial (n = 41), or
      ovarian cancer (n = 13). Lymphadenectomy was combined with laparoscopically
      assisted vaginal radical hysterectomy in 70 patients, with laparoscopically
      assisted vaginal hysterectomy and/or bilateral salpingo-oophorectomy and/or
      appendectomy and/or omentectomy in 24 patients, with trachelectomy in 2 patients,
      and with laparoscopic radical hysterectomy in 2 patients; lymphadenectomy alone
      was performed in 52 patients. Right-sided para-aortic lymphadenectomy extended to
      the level of the right ovarian vein; left-sided dissection reached the level of
      the inferior mesenteric artery. In ovarian tumors, dissection was extended to the
      level of the renal vessels; in addition, the ovarian vessels were removed with
      the surrounding tissue. Peri- and postoperative data were collected prospectively
      to monitor progress of surgical performance. RESULTS: Mean operative time was 36
      min (15-105 min) for right-sided para-aortic and 24 min (12-49 min) for left
      sided para-aortic lymphadenectomy; bilateral pelvic lymphadenectomy took 64 min
      (44-110 min). On average 26.8 (10-56) pelvic lymph nodes and 7.3 (0-19) para
      aortic lymph nodes were sampled. Major vessels were injured in 7 patients of
      which 4 patients required laparotomy. Patients undergoing lymphadenectomy alone
      were admitted for 3.2 days on average. CONCLUSIONS: Laparoscopic para-aortic and
      pelvic lymphadenectomy is effective for staging and treatment of gynecologic
      cancers.

PMID- 9784315
TI  - The effects of platelet-derived growth factor and receptor on normal and
      neoplastic human ovarian surface epithelium.
AB  - Several growth factors have been shown to stimulate or inhibit the growth of
      human ovarian surface epithelial (HOSE) cells. Platelet-derived growth factor
      (PDGF) is likely to be released onto the ovarian surface epithelium during
      follicular wound repair. We undertook the evaluation of this factor and its
      receptor in normal and malignant ovarian cells. OBJECTIVES: The goal of this
      study was to evaluate the response of HOSE cells to PDGF in vitro and identify
      PDGF receptors on normal and malignant ovarian epithelial cells. In addition, we
      wanted to examine the prognostic value of the PDGF receptors in clinical
      specimens. METHODS: Normal HOSE cells were cultured and growth response to PDGF
      assayed by 3H uptake. PDGF receptor status on HOSE cells, established ovarian
      carcinoma cell lines, and paraffin tissue was performed by immunohistologic
      techniques. Data on ovarian cancer patients relapse-free survival (RFS) were
      abstracted from the Lankenau Hospital Tumor Registry and RFS was plotted using
      the Kaplan-Meier method. RESULTS: HOSE cells increased 3H uptake in a dose
      dependent manner in response to PDGF. HOSE cells stain positively for both alpha
      and beta receptors, as does the chemotherapy naive cell line A2780. The platinum
      resistant CP30 cell line loses PDGF alpha staining. Of 21 ovarian cancer
      specimens, only 1 retained PDGF alpha receptors while 8 retained PDGF beta
      receptors. Those patients positive for PDGF receptor beta had a significantly
      longer relapse-free survival than PDGF beta receptor-negative patients.
      CONCLUSIONS: PDGF enhances the growth of HOSE cells in vitro and may play a role
      in ovarian cancer development. Patients whose tumors retain PDGF receptor beta
      staining positivity have a prolonged relapse-free survival.

PMID- 9784316
TI  - Underexpression of cyclin-dependent kinase (CDK) inhibitors in cervical
      carcinoma.
AB  - Recent studies have revealed a new family of tumor suppressor genes that directly
      implicate aberrant cell cycle regulation in tumorigenesis. The general function
      of these gene products is that they prevent cell cycle progression by directly
      interfering with cyclin/cyclin-dependent kinase (CDK) activation. The importance
      of these genes is that they are potent inhibitors of CDK. Among these cell cycle
      inhibitors, p21(WAF1/CIP1) and p16 have been thoroughly studied. However, the
      role of p21(WAF1/CIP1) and p16 in the tumorigenesis of the uterine cervix has
      been poorly defined. We used immunohistochemical techniques to study the
      expression of these cell cycle inhibitors in formalin-fixed, paraffin-embedded
      cervical tissue to explore the relationship between cyclin/CDK inhibitors and
      cervical carcinoma. Cervical tissues were analyzed from 46 patients with cervical
      carcinoma, 30 cases with cervical intraepithelial neoplasia (CIN) and 22 control
      cases who underwent hysterectomy due to benign gynecologic disease at Yonsei
      University College of Medicine. All CDK inhibitors were strongly expressed in the
      reverse cell hyperplasia and koilocytes, whereas they revealed significantly
      decreased expression in neoplastic tissues (P < 0.05). P16 revealed higher
      expressions in cases associated with human papillomavirus (HPV) (t test, P <
      0.05) than in cases lacking any type of HPV. Our results were consistent with the
      concept that underexpression of CDK inhibitors may play an important role in
      neoplastic transformation in cervical carcinoma.

PMID- 9784317
TI  - The pre- and postoperative value of endocervical curettage in the detection of
      cervical intraepithelial neoplasia and invasive cervical cancer.
AB  - OBJECTIVE: The study was conducted to evaluate the pre- and postoperative value
      of endocervical curettage (ECC) in the detection of cervical intraepithelial
      neoplasia and invasive cervical cancer. METHODS: Patients undergoing cervical
      conization were studied retrospectively to evaluate the correlation of grade of
      preoperative endocervical curettage and the grade of dysplasia in the conization
      specimen. The role of routine preoperative ECC in satisfactory and unsatisfactory
      colposcopy and the need for routine ECC in the detection of postoperative
      residual dysplasia was also evaluated. RESULTS: Results showed that 297/391 (76%)
      patients had ECC as part of preoperative assessment for cervical dysplasia on
      Papanicolaou smear. There was good association of grade of preoperative ECC and
      grade of conization specimen, weighted kappa-0.135 (P = 0.0003). Of 17 patients
      with invasive disease on conization specimen, only patients with a positive ECC
      had invasion at conization. None of 113 patients with a negative preoperative ECC
      had invasive disease on their conization specimens. The proportion of
      satisfactory colposcopic examinations between positive and negative ECC is not
      significantly different (P = 0.673). Follow-up of positive margins of resection
      was performed with Papanicolaou smear in only 20 patients and with Papanicolaou
      smear and ECC in 53 patients. In the latter group, 4% had a positive ECC with
      negative Papanicolaou smear (P = 0.310). CONCLUSIONS: There is good agreement
      between grade of dysplasia on preoperative ECC and on subsequent conization
      specimen. Colposcopic examination was not a good predictor of pathology in the
      endocervical canal. Routine ECC should be part of the preoperative assessment of
      an abnormal Papanicolaou smear but may be unnecessary in the evaluation for
      residual dysplasia.

PMID- 9784318
TI  - Radical hysterectomy with the endoscopic stapler.
AB  - OBJECTIVE: Morbidity associated with radical hysterectomy is significant.
      Utilizing the endoscopic stapler for transection of the cardinal ligaments and
      uterosacral ligaments is a possible method to decrease operative time and blood
      loss. METHODS: Two groups of patients, one group with the stapler used (n = 21)
      and the other with the traditional method utilized (n = 18), were compared in
      regard to operative and postoperative morbidity, operative time, and surgical
      margins. The groups were similar in regard to medical condition, age, and weight.
      RESULTS: Median (243 min versus 284 min) and mean (246 min versus 287 min)
      operative times were significantly less in the stapler group than in the control
      group (P < 0.002). Median blood loss was reduced by 20% in the stapler group (400
      ml versus 500 ml, P < 0.03). There was no significant difference in febrile
      morbidity, surgical complications, or length of hospital stay. CONCLUSION: Our
      data suggest significant reduction in blood loss and operative time with the use
      of the endoscopic stapler.

PMID- 9784319
TI  - Microsatellite instability and somatic mutations in endometrial carcinomas.
AB  - Recently, microsatellite instability (MI) has been demonstrated in some types of
      human cancers. In this study, we attempted to determine the frequency of MI in
      endometrial cancers and evaluate whether replication error (RER)-positive
      phenotype is correlated with known genetic mutations or the aberrations of other
      pathways in endometrial cancers. Seventy-two primary endometrial cancers were
      examined for microsatellite instability. Eleven tumors (15%) had RERs at two or
      more microsatellite loci, suggesting that generalized MI may be a molecular
      manifestation of endometrial cancers. We next examined whether the MI was
      associated with changes in the K-ras protooncogene, p53 tumor suppressor gene,
      and 18q LOH, which were frequently detected in endometrial cancers. The MI did
      not confer the potential to produce point mutations in the K-ras gene or 18q LOH,
      whereas the data were insufficient to identify the correlation between MI and p53
      mutations in the cancers. These results suggest the presence of multiple mutation
      subsets that act in a complementary fashion in endometrial cancer development.

PMID- 9784320
TI  - p53 protein overexpression: a strong prognostic factor in uterine papillary
      serous carcinoma.
AB  - Uterine papillary serous carcinoma (UPSC) is an uncommon but aggressive type of
      endometrial cancer associated with rapid progression of disease and poor
      prognosis. We investigated 23 cases of UPSC. p53 expression was studied in
      archival paraffin-embedded tissue by immunohistochemistry. Eleven tumors (47.8%)
      showed p53 overexpression whereas 12 tumors (52.2%) were p53 negative. One of 8
      stage I/II (12.5%) and 10/15 stage III/IV (66.6%) tumors revealed p53 staining (P
      = 0.027). The median overall survival was 43.3 months. Patients with advanced
      stage (III, IV) disease had a 5-year overall survival probability (5-year OS%) of
      24% compared to 100% in those in stages I and II (log-rank, P = 0.018).
      Myometrial invasion, lymphatic space invasion, or lymph node involvement did not
      correlate with the 5-year OS of these patients. Patients whose tumors
      overexpressed p53 had a significantly shorter survival than those whose tumors
      did not (P = 0.033). This study confirms the influence of p53 overexpression on
      survival in UPSC patients.

PMID- 9784321
TI  - Selective potentiation of gynecologic cancer cell growth in vitro by
      electromagnetic fields.
AB  - OBJECTIVE: Epidemiological data suggest that exposure to electromagnetic fields
      (EMF) may increase the risk of various cancers. We evaluated EMF effects on the
      in vitro growth response of human cell lines isolated from various reproductive
      tract tissues. We also assessed the effects of EMF on cisplatin- or paclitaxel
      induced cytotoxicity. METHODS: Endometrial, ovarian, and prostate cancer cell
      lines as well as immortalized endometrial stromal cells and immortalized ovarian
      epithelial cells were exposed continually to EMF. Proliferation was assessed by
      the metabolic activity assay, MTT, direct cell counting, and anchorage
      independent colony formation in soft agar. Cytotoxicity induced by cisplatin or
      paclitaxel was assessed using the MTT assay. RESULTS: Continuous exposure to EMF
      at field strengths of 2 G enhanced proliferation of two human prostate and three
      endometrial, but only one ovarian, cancer cell lines. EMF enhanced metabolic
      activity of cancer cells within 96 h and increased absolute cell number
      (anchorage-dependent proliferation) and colony-forming efficiency (anchorage
      independent proliferation) over sham-treated controls. EMF had no effect on
      cytotoxicity induced by the chemotherapeutic agents Taxol or cisplatin.
      CONCLUSIONS: Continuous exposure to EMF can enhance growth rates of transformed
      cells for some human epithelial cancers. Cancer cells from the steroid sex
      hormone regulated tissues of endometrium and prostate appeared to be more
      responsive to EMF than cells from ovarian cancers.

PMID- 9784322
TI  - Adjuvant vaginal high-dose-rate afterloading alone in endometrial carcinoma:
      patterns of relapse and side effects following low-dose therapy.
AB  - OBJECTIVE: This retrospective study was conducted to document the incidence and
      location of recurrences as well as the rate of side effects following low-dose
      postoperative high-dose-rate (HDR) brachytherapy in patients with endometrial
      carcinoma. METHODS: From 1987 to 1993, 122 patients with moderate-risk (78) and
      high-risk (44) endometrial carcinoma underwent adjuvant vaginal irradiation. All
      patients received three fractions of 7 Gy specified on the surface of the vaginal
      cylinder. RESULTS: Relapses occurred in 12 (9. 8%) patients on average after 25.6
      months. Seven (5.7%) patients had a sole pelvic recurrence; in 2 (1.6%) of those
      the relapse was located in the vagina only. Three (2.5%) patients had a pelvic
      relapse combined with distant metastases. Distant metastases alone were diagnosed
      in 2 (1.6%) patients. A tumor recurrence was diagnosed in 3 of 78 (3.8%) patients
      with moderate-risk disease and in 9 of 44 (20.5%) patients with high-risk
      disease. The estimated 5-year relapse-free survival was 94% for patients with
      moderate-risk and 74% for patients with high-risk tumors (P = 0.004). Neither
      severe nor chronic complications were noted. CONCLUSION: Even low doses of HDR
      brachytherapy seem sufficient for excellent vaginal disease control in moderate
      risk disease. In advanced tumors combined radiation therapy is warranted for
      improved pelvic disease control.

PMID- 9784323
TI  - Analysis of allelic imbalance on chromosome 17p13 in stage I and stage II
      epithelial ovarian cancers.
AB  - OBJECTIVES: To determine whether there is evidence for allelic imbalance (AI) on
      chromosome 17p13 in early-stage epithelial ovarian tumors. METHODS: Studies of
      allelic imbalance were performed on 29 stage I or stage II epithelial ovarian
      cancers using 5 short tandem repeat polymorphic markers (STRPs) on chromosome
      17p13 by polymerase chain reaction (PCR) amplification. RESULTS: Sixteen of 29
      (55%) tumors showed AI at one or more loci, including 7 of 29 (24%) tumors that
      showed distinct regions of AI. AI at p53 was present in only 9 of 25 (36%)
      informative tumors. A region of AI, defined by marker D17S654, close to candidate
      genes OVCA1 and OVCA2, was identified distal to p53 and occurred in 11 of 23
      (48%) informative tumors. This region of AI also extended more distal to this
      locus, and included marker D17S695 where AI occurred in 11 of 26 (42%)
      informative tumors. Microsatellite instability was observed in 2 of 29 tumors.
      CONCLUSIONS: This study supports the presence of at least one tumor suppressor
      gene on chromosome 17p13 distal to p53 that is involved in the early development
      of epithelial ovarian cancer. This study also suggests that the molecular
      analysis of early-stage epithelial ovarian cancers can provide important
      information on the genetic etiology of ovarian cancers.

PMID- 9784324
TI  - Papillary serous and clear cell carcinoma limited to endometrial curettings in
      FIGO stage 1a and 1b endometrial adenocarcinoma: treatment implications.
AB  - OBJECTIVE: The aim of this study was to review the significance of papillary
      serous and clear cell carcinoma in Stage 1a and 1b adenocarcinoma of the
      endometrium where this histological subtype is confined to the endometrial
      curettings and is absent in the hysterectomy specimen. METHODS AND MATERIALS:
      Three hundred twenty patients with Stage 1a or 1b adenocarcinoma of the
      endometrium without lymphovascular space invasion or evidence of FIGO Grade 3
      histology demonstrated in the hysterectomy specimen were referred to the British
      Columbia Cancer Agency, Vancouver Clinic, between January 1992 and July 1995.
      These charts were retrospectively reviewed. RESULTS: On pathology review, eight
      patients were found to have evidence of papillary serous or clear cell carcinoma
      confined to the uterine curettings. Five patients also had Grade 1 or 2
      endometrioid adenocarcinoma without lymphovascular space involvement seen in the
      hysterectomy specimen. All patients were managed expectantly. None of these 8
      have recurred with a median follow-up of 3 years. CONCLUSION: A clinical dilemma
      arises when there is evidence of papillary serous or clear cell carcinoma limited
      to the endometrial curettings where there is no associated adverse pathological
      features seen in the hysterectomy specimen. In our series of patients treated
      expectantly, it appears that a small bulk of aggressive disease seen only in the
      curettage specimen does not adversely impact disease-free survival.

PMID- 9784326
TI  - Treosulfan as an effective second-line therapy in ovarian cancer.
AB  - Despite radical surgery and aggressive platinum-containing primary chemotherapy,
      the outcome of patients with advanced ovarian cancer remains extremely poor; most
      of them suffer from recurrent or progressive disease. These patients should be
      treated with an effective second-line therapy showing only few toxic side effects
      so as not to affect quality of life. From July 1992 to August 1996, 88 patients
      with recurrent or progressive ovarian cancer have been treated with treosulfan,
      an alkylating agent, in our department. All of them could be evaluated for
      toxicity and 80 for response. There were 2 complete and 13 partial responses,
      giving an objective response rate of 19%. Among responding patients, median
      survival time was 41 months. Thirty-four percent of the patients had stable
      disease with median survival of 18 months. Thirty-eight (47%) nonresponding
      patients showed a survival time of only 5 months. In 48 women with progressive
      disease within 12 months after primary therapy, a response rate of 19% and stable
      disease in 31% could be achieved. Toxic side effects were rare and moderate in
      intensity. Life-threatening myelosuppression, emesis resistant to therapy, and
      alopecia were not observed. It can be concluded that tresosulfan is an effective
      drug in second-line therapy for patients with recurrent or progressive ovarian
      cancer without affecting quality of life.

PMID- 9784325
TI  - New development of laparoscopic ultrasound and laparoscopic pelvic
      lymphadenectomy in the management of patients with cervical carcinoma.
AB  - OBJECTIVES: The objectives of this study were to evaluate the use of laparoscopic
      ultrasonography (USG) in combination with laparoscopic pelvic lymphadenectomy in
      the management of patients with cervical carcinoma. METHODS: A technique for
      detecting pelvic and para-aortic lymph node metastases through laparoscopic USG
      was developed. Laparoscopic USG was done prior to pelvic lymphadenectomy
      performed either laparoscopically or by laparotomy. Laparoscopic USG findings
      were compared with pathologic findings. RESULTS: The sensitivity and specificity
      of laparoscopic USG in detecting pelvic lymph node metastases were 91 and 100%,
      respectively. Metastatic pelvic lymph nodes could be completely removed through
      laparoscopes in 7 of 11 patients, with no complications. CONCLUSION: Laparoscopic
      USG is highly sensitive in detecting metastatic pelvic lymph nodes. Detection and
      removal of metastatic pelvic lymph nodes laparoscopically allow quick recovery
      from the operation and early commencement of radiotherapy.

PMID- 9784327
TI  - Effect of acetic acid on telomerase activity in cervical intraepithelial
      neoplasia.
AB  - OBJECTIVE: To evaluate whether the telomerase activity in CIN lesions can be
      affected by a chemical solution of acetic acid, which is required to apply to the
      cervix prior to colposcopy-directed biopsy. MATERIALS AND METHODS: Thirty-five
      patients with histologically confirmed high-grade squamous intraepithelial
      lesions of the cervix entered the study. Two specimens were collected from each
      patient, one before and one after the cervix was swabbed with 5% acetic acid. The
      standard telomeric repeat assay protocol (TRAP) was used to examine telomerase
      activity in these fresh frozen tissue samples. Normal cervical tissues from 10
      control individuals were also examined for the presence of telomerase activity. A
      total of 80 specimens was analyzed. RESULTS: Telomerase activity was detectable
      in 27 of 35 (77.1%) fresh tissue samples, 15 of 35 (42.9%) tissue samples swabbed
      with 5% acetic acid, and 0 of 10 (0%) normal cervical tissue samples,
      respectively. Twelve samples became telomerase negative after 5% acetic acid
      applied. Among the 15 telomerase-positive tissue samples swabbed with 5% acetic
      acid, 12 had relative weak telomerase activity compared to corresponding fresh
      tissue samples, the other 3 remained the same. Therefore, it is concluded that
      telomerase activity was affected by 5% acetic acid in 24 of 27 (88.9%) samples.
      Telomerase activity in HeLa cell line was also inhibited by 5% acetic acid.
      CONCLUSION: We reported a relative high percentage of telomerase expression in
      high-grade CIN lesions when compared with previous reports. If detection of
      telomerase activity is to become a tool for diagnosis and prognosis of cervical
      neoplasias, applying acetic acid prior to colposcopy-directed biopsy that is
      submitted for telomerase assay should be avoided in order to increase the
      detection rate.

PMID- 9784329
TI  - Subsequent reproductive experience after treatment for gestational trophoblastic
      disease.
AB  - PURPOSE: The purpose of this study was to evaluate reproductive performance of
      patients with gestational trophoblastic disease (GTD) after completion of
      treatment and follow-up periods. PATIENTS AND METHODS: Subjects comprised 115
      patients who became pregnant after having been judged completely cured after a
      follow-up period of at least 1 year. There were 77 hydatidiform-mole patients who
      had a natural cure and 38 gestational trophoblastic tumor patients who were cured
      after chemotherapy. We studied these patients with respect to parameters
      concerning pregnancy outcome. RESULTS: Average age at first pregnancy was 28.0
      and average number of past deliveries was 1.3. After a 1-year contraception
      period, the average time to the next pregnancy was 0.8 year, with 59 of 115
      (51.3%) women becoming pregnant within 1 year after pregnancy was permitted and
      98 women (85.2%) conceiving within 3 years. Results of the pregnancies after cure
      of GTD did not deviate from normal ranges in separated analyses of complete mole
      (CM), partial mole (PM), and gestational trophoblastic tumor. Rate of repeat mole
      was found to be high, occurring in 5 of 115 (4.3%) cases. Rates of antepartum and
      postpartum complications did not deviate from normal ranges, and there was
      nothing peculiar about the neonatal sex and weight. CONCLUSION: GTD and
      chemotherapy rarely affect later pregnancies; however, the rate of repeat mole is
      relatively high.

PMID- 9784328
TI  - Gastrointestinal toxicity and Clostridium difficile diarrhea in patients treated
      with paclitaxel-containing chemotherapy regimens.
AB  - OBJECTIVE: The objective of this study was to determine the incidence of grade 3
      and 4 gastrointestinal toxicity and the prevalence of Clostridium difficile
      associated diarrhea (CDAD) in patients with gynecologic malignancies treated with
      paclitaxel-based chemotherapy regimens. METHODS: We retrospectively reviewed the
      medical records of all patients treated on the Gynecology Service at Memorial
      Sloan-Kettering Cancer Center from January 1, 1993 to July 1, 1996. We identified
      all patients treated with paclitaxel during this period and determined the total
      number of patients hospitalized for symptoms of gastrointestinal toxicity,
      including nausea, vomiting, diarrhea, and dehydration, within 4 weeks of
      chemotherapy, as well as the incidence of CDAD among these patients. RESULTS: Six
      hundred and twenty-four patients were treated with paclitaxel-containing
      chemotherapy regimens during the study period, including 55 patients who were
      treated on a "dose-dense" high-dose protocol for advanced ovarian cancer. Among
      these, 149 patients (24%) were hospitalized for symptoms of gastrointestinal
      toxicity. During the study period, a total of 40 cases of CDAD were reported
      among hospitalized patients on the Gynecology Service and 24 (60%) of these cases
      occurred in patients who had received paclitaxel within the prior 4 weeks.
      CONCLUSIONS: The occurrence of CDAD in patients receiving paclitaxel-containing
      chemotherapy is not rare and can result in severe dehydration requiring
      hospitalization. The risk of C. difficile colitis appears to be 2.2% in patients
      receiving standard-dose regimens and as high as 20% in patients receiving high
      dose regimens. This etiology should be considered and treated early in patients
      presenting with symptoms of gastrointestinal toxicity subsequent to chemotherapy
      treatments.

PMID- 9784330
TI  - Low-dose oral granisetron (1 mg) plus intravenous dexamethasone: efficacy in
      gynecologic cancer patients receiving carboplatin-based chemotherapy.
AB  - OBJECTIVE: The objective of this study was to determine the efficacy of a low
      dose oral granisetron plus intravenous dexamethasone prophylactic antiemetic
      regimen in patients receiving carboplatin-based chemotherapy. PATIENTS AND
      METHODS: Patients with gynecologic malignancies being treated with either single
      agent carboplatin or a carboplatin-paclitaxel regimen received a single 1-mg oral
      dose of granisetron 30 min prior to chemotherapy plus intravenous dexamethasone
      (20 mg) as prophylaxis for emesis. Patients either had not previously been
      treated with chemotherapy or had not received any cytotoxic drugs for >/=4 months
      prior to study entry. Effectiveness was evaluated based on the degree of control
      of nausea and vomiting during the 24 h following treatment. RESULTS: Of the 32
      patients participating in this phase 2 trial, only 2 (6%) experienced any degree
      of nausea or vomiting within the first 24 h of chemotherapy administration. Both
      of these individuals had carcinomatosis and were experiencing emesis prior to
      chemotherapy. One patient developed mild delayed nausea >24 h after treatment. No
      major or minor toxic effects of the antiemetic regimen observed. CONCLUSION: A 1
      mg dose of oral granisetron plus intravenous dexamethasone (20 mg) is a safe,
      effective, and relatively inexpensive prophylactic antiemetic regimen for
      patients receiving single-agent carboplatin or combination carboplatin-paclitaxel
      chemotherapy.

PMID- 9784331
TI  - Primary squamous cell cancer of the vulva: radical versus modified radical vulvar
      surgery.
AB  - OBJECTIVE: To evaluate the results of surgical therapy and to specifically
      compare radical and modified radical vulvar surgery relative to survival,
      recurrence, metastasis, and complications. METHODS: A retrospective review of 225
      patients with primary squamous cell cancer of the vulva was performed. Clinical,
      pathologic, surgical, and follow-up data were collected from the patient records.
      All pathology slides were reviewed with a pathologist. Radical surgery included
      134 patients treated by the Basset operation. Modified radical surgery accounted
      for 91 patients with vulvar excision alone (65) or with lymphadenectomy (26) via
      separate groin incisions. RESULTS: The 5-year recurrence rate was 14%. The
      overall and disease-free survival rates at 5 years were 76. 1 and 83.4%,
      respectively. There were no statistically significant differences between the two
      procedures regarding overall survival, disease-free survival, or the development
      of recurrence, even after adjusting for stage (P > 0.05). Patients undergoing
      radical vulvar surgery were more likely to develop surgical complications and
      sequelae than patients having modified radical surgery, even after adjusting for
      stage. CONCLUSIONS: Modified radical vulvar surgery is associated with decreased
      complications and 5-year overall and disease-free survival and recurrence rates
      similar to those of radical vulvar surgery.

PMID- 9784332
TI  - CD31 expression in benign, borderline, and malignant epithelial ovarian tumors:
      an immunohistochemical and serological analysis.
AB  - OBJECTIVE: To evaluate (a) the expression of CD31 in benign, borderline, and
      maligant ovarian tumors; (b) the correlation between CD31 expression and the
      clinicopathological parameters; and (c) the diagnostic interest of serological
      soluble CD31 (sCD31) in patients with ovarian tumors. METHODS: The intratumoral
      microvessel density was evaluated by an immunohistochemical technique with the
      monoclonal antibody JC70 against CD31 at two dilutions in 20 benign, 20
      borderline, and 20 malignant tumors of the ovary. Serological determinations of
      sCD31 with ELISA technique was performed in 35 patients with ovarian tumors (24
      benign, 5 borderline, and 6 malignant tumors). RESULTS: The expression of CD31
      was higher in ovarian carcinomas than in borderline and benign tumors (P < 0.001)
      irrespective of the dilutions of the antibody used. In ovarian carcinomas, a
      correlation was observed between CD31 expression and the stage of the disease,
      the histologic type, the degree of histological differentiation, and the survival
      of the patients. In borderline tumors, no correlation was noted between CD31
      expression and the clinicopathologic parameters. No difference in serological
      levels of sCD31 was noted according to histologic types. CONCLUSION: CD31
      immunostaining may have a prognostic relevance in ovarian carcinoma but seems to
      be of limited value in borderline tumors. Serological levels of sCD31 have no
      diagnostic interest in ovarian tumors.

PMID- 9784333
TI  - Neuroendocrine small cell uterine cervix cancer in pregnancy: long-term survival
      following combined therapy.
AB  - A 22-year-old woman carrying twin gestations at 30 weeks presented with preterm
      labor and a prolapsing cervical mass. Following Cesarean section birth, she was
      treated with multiagent chemotherapy followed by pelvic radiotherapy for a Stage
      IIA small cell cancer of the uterine cervix. She is without evidence of disease
      5.5 years after diagnosis and is the first reported long-term survivor of a small
      cell cervical carcinoma diagnosed during pregnancy.

PMID- 9784334
TI  - Ovarian endometrioid adenocarcinoma with ectopic production of alpha-fetoprotein.
AB  - alpha-Fetoprotein (AFP) is well known as a tumor marker of ovarian endodermal
      sinus tumor or embryonal carcinoma in gynecological malignancies. However, AFP
      production is extremely rare in ovarian epithelial cancers. Here we report a case
      of a 53-year-old woman with an AFP-producing ovarian endometrioid adenocarcinoma.
      The serum AFP level was elevated up to 2759 ng/ml preoperatively, with a
      subsequent decrease to the normal range after treatment. Histological examination
      of the tumor revealed a well-differentiated endometrioid adenocarcinoma with
      small foci of clear cell components. None of endodermal sinus tumor, hepatoid
      carcinoma, or embryonal carcinoma components were observed. Immunohistochemical
      analysis revealed that AFP was expressed in the cytoplasm of the endometrioid
      glandular lesions, but not in the clear cell components. This is probably the
      first case of a pure type of ovarian endometrioid adenocarcinoma with significant
      levels of AFP expression.

PMID- 9784335
TI  - Synchronous Paget's disease of the vulva and breast.
AB  - We report the first case of synchronous Paget's disease of the vulva and breast
      diagnosed within a period of 7 months. This is the fourth case of mammary Paget's
      disease associated with either preceding or following vulvar Paget's disease
      documented in the literature. With consideration of increasing age of the
      population, and the fact that vulvar Paget's disease affects elderly women and
      that breast cancer is the most common malignancy of women in the United States,
      one can anticipate the occurrence of these two conditions to be more prevalent in
      the future.

PMID- 9784336
TI  - Two cases of endometrial adenocarcinoma arising from atypical polypoid
      adenomyoma.
AB  - Atypical polypoid adenomyoma (APA) most frequently presents as an endometrial
      polyp in premenopausal women and is believed to follow a benign course. In
      hysterectomy specimens from postmenopausal Japanease women, the endometrium
      contained an APA with an area of endometrial adenocarcinoma. A convincing
      transition zone between the APA and the adenocarcinoma was seen in our cases,
      suggesting that APA may develop into endometrial adenocarcinoma in postmenopausal
      women.

PMID- 9784337
TI  - Hysteroscopic dissemination of endometrial carcinoma.
AB  - BACKGROUND: In patients with endometrial carcinoma, the use of hysteroscopy may
      result in malignant peritoneal cytology. The significance of these mechanically
      disseminated malignant cells is uncertain. CASE: Disseminated endometrial
      carcinoma occurred in a 39-year-old patient with endometrial carcinoma which had
      been hysteroscopically resected and treated conservatively. Hysteroscopic
      dissemination was strongly suggested based on the limited extent of carcinoma in
      the uterus, the exophytic nature of the pelvic tumor implant, and the lack of
      associated endometriosis. CONCLUSION: Hysteroscopy should be reserved for
      patients in whom prior endometrial sampling fails to demonstrate malignancy.

PMID- 9784339
TI  - Genetic diversity in insect-parasitic nematodes (Rhabditida: heterorhabditidae)
AB  - Little is known about the genetic structure of various species and populations of
      entomopathogenic nematodes. We determined genetic variability within and among
      isolates of seven Heterorhabditis species using random amplified polymorphic DNA
      (RAPD) markers. We used 10 random primers which were previously identified as
      useful to quantify genetic variability among these species. Mean percentage
      similarity among the individuals of conspecific species was 96.25%, whereas, the
      mean value among different isolates for three species was 83.8%. Mean percentage
      similarity among different species was 31. 3%. The banding patterns produced by
      RAPDs positively correlated with described morphological classification; however,
      H. hawaiiensis could not be separated from H. indicus, or H. marelatus from H.
      hepialius. RAPD profiles placed an unidentified isolate (IS5) with H. indicus.
      Copyright 1998 Academic Press.

PMID- 9784340
TI  - Differentiation of beauveria bassiana isolates from the darkling beetle,
      alphitobius diaperinus, using isozyme and RAPD analyses
AB  - Two natural genetic markers, isozymes and RAPD, were utilized to differentiate 24
      strains of Beauveria bassiana (Deuteromycotina: Hyphomycetes) collected from the
      darkling beetle, Alphitobius diaperinus (Coleoptera: Tenebrionidae), from poultry
      houses in North Carolina and West Virginia. Nine enzyme systems were screened, of
      which alkaline phosphatase, alpha- and beta-esterase, and glucose phosphate
      isomerase gave well-resolved, scorable bands. A total of 26 isozyme bands was
      generated by these four enzymes which partitioned the 24 strains into 14 classes.
      Three classes were shared by two or more strains while the rest of the strains
      had distinct electrophoretic profiles. Ten RAPD primers, selected from 72 that
      were screened, produced 141 bands from the 24 strains and separated each as a
      unique class. While both systems were able to detect variation present among the
      24 strains from different regions in North Carolina and West Virginia, RAPD
      markers provided better resolution of the differences between strains. Variation
      was detected not only within and among strains from different regions but also
      among strains collected from a given insect host. Copyright 1998 Academic Press.

PMID- 9784341
TI  - Penetration of the entomopathogenic nematode heterorhabditis spp. into host
      insects at 9 and 20 degreesC
AB  - Biological control of black vine weevil, Otiorhynchus sulcatus, by means of the
      entomopathogenic nematode, Heterorhabditis spp., is difficult to obtain at low
      temperatures. The influence of temperature on nematode penetration ability was
      investigated to identify whether this process is a bottleneck for biocontrol.
      Variation in penetration ability among and within Heterorhabditis was assessed. A
      negative exponential model was used to characterize penetration in time. The two
      parameters in this model, the proportion of infectious nematodes and their
      relative penetration rate, were compared among different batches of the same
      nematode isolate (HF85). There was a considerable amount of nongenetic variation
      among batches of HF85, stored for different periods of time, in the proportion of
      infectious nematodes, but there was little variation in the relative penetration
      rate. There was almost no (genetic) variation in the proportion of nematodes that
      is infectious against O. sulcatus at 9 degreesC among 12 heterorhabditid
      isolates. Variation did occur when two lepidopteran species, Galleria mellonella
      and Spodoptera exigua, were offered as hosts at 9 degreesC or when hosts were
      presented at 20 degreesC. The relevance of variation in penetration parameters
      for control of O. sulcatus at low temperatures is discussed. Copyright 1998
      Academic Press.

PMID- 9784342
TI  - Expression of chromosomally inserted bacillus thuringiensis israelensis toxin
      genes in bacillus sphaericus
AB  - Bacillus thuringiensis israelensis delta-endotoxin genes were inserted into
      transposon Tn917 in plasmid pTV51Ts and cloned into the chromosome of Bacillus
      sphaericus 2362. Many of the transformants reacted with antibody to the 135-, 128
      , 65-, and 28-kDa B.t.israelensis toxin proteins and were approximately 10 times
      more toxic to A. aegypti larvae than the untransformed host. Some of the
      transformants differed physiologically and morphologically from the wild-type B.
      sphaericus. The toxicity of the transformed phenotype was maintained through many
      transfers in the absence of selective pressure. Copyright 1998 Academic Press.

PMID- 9784343
TI  - The turbellarian urastoma cyprinae from edible mussels mytilus galloprovincialis
      and mytilus californianus in baja california, NW Mexico
AB  - The turbellarian Urastoma cyprinae (Graff, 1913) was found in the mantle cavity
      of Mytilus galloprovincialis Lamarck and Mytilus californianus Conrad, on the
      Pacific coast of Baja California NW Mexico. This is the first record of this
      turbellarian for bivalves from the Pacific coast of North America. In M.
      galloprovincialis from an exposed rocky shore, prevalence ranged from 10 to 87%
      and mean number of turbellarians per infested mussel was 1.9; in a culture area
      prevalence ranged from 57 to 100% and the mean number of turbellarians per
      infested mussel was 7.4. In the protected and polluted areas U. cyprinae was
      scarce or absent, prevalence ranging from 0 to 15% and the mean number of
      turbellarian per infested mussel being 0.07. The prevalence and the mean number
      of turbellarians per M. californianus in the exposed rocky shore ranged from 20
      to 100% and 5.1, respectively. There were more worms in the larger mussels.
      Demibranches of M. galloprovincialis and M. californianus may be injured by the
      presence of turbellarians. An infiltration of hemocyte cells around the
      turbellarians was observed in both species and the blood sinuses in the infected
      area were engorged. Recorded damage was not related to a negative effect on the
      condition index of mussels. Copyright 1998 Academic Press.

PMID- 9784344
TI  - Conidial attachment of metarhizium anisopliae and beauveria bassiana to the
      larval cuticle of diaprepes abbreviatus (Coleoptera: curculionidae) treated with
      imidacloprid
AB  - A series of experiments was conducted to determine the effect of imidacloprid on
      the number of Metarhizium anisopliae and Beauveria bassiana conidia found on the
      cuticle of first instar Diaprepes abbreviatus following different treatments.
      Larvae treated with M. anisopliae conidia and imidacloprid by dipping removed
      significantly fewer conidia from their cuticle when in contact with soil or a
      food source compared with fungal-treated larvae alone. In addition, more M.
      anisopliae and B. bassiana conidia were found on the cuticle of larvae treated
      with imidacloprid while exposed to soil at 7 and 14% moisture resulting in higher
      larval mortality and mycosis. Conidial attachment to cuticles of untreated larvae
      was higher at <1% compared with 7 and 14% soil moistures. M. anisopliae conidia
      were distributed uniformly over the pleural membrane of the larval cuticle of
      both untreated and imidacloprid-treated larvae. However, fewer conidia were
      attached to specific sites such as setae and setal sockets of treated larvae. At
      12 h after treatment, imidacloprid-treated larvae had fewer conidia removed from
      exposed cuticle, setae, and spiracles than did untreated larvae. Cuticular
      exposure to imidacloprid at doses >0.01% (AI) affected conidial attachment of M.
      anisopliae negatively. Conidial number decreased sevenfold at 0.1% (AI).
      Comparative data on the effect of imidacloprid formulation on conidial attachment
      showed that components of the inert ingredient were responsible for lower
      conidial attachment on larval cuticle at higher insecticidal doses. Copyright
      1998 Academic Press.

PMID- 9784345
TI  - A nonpermissive entomophthoralean fungal infection increases activation of insect
      prophenoloxidase
AB  - Entomophaga maimaiga and Entomophaga aulicae are entomopathogenic fungi that show
      species-specific infection in Lepidoptera. These fungi grow as protoplasts in the
      hemolymph of permissive insect hosts. E. maimaiga infects gypsy moth larvae,
      Lymantria dispar, and E. aulicae infects hemlock looper, Lambdina fiscellaria.
      Cross-infections do not occur and are referred to as a nonpermissive response. We
      circumvented cuticular barriers and injected E. aulicae protoplasts into L.
      dispar and investigated factors which could potentially curtail entomophthoralean
      fungal infection in a nonpermissive host insect. There was no evidence of (i)
      restricted fungal growth in cell-free hemolymph of the nonpermissive host, (ii)
      fungal toxins specific to host insect, (iii) hemocyte encapsulation of fungal
      protoplasts in a nonpermissive or permissive infection, or (iv) fungal-specific
      induction of plasma proteins in L. dispar. However, higher levels of
      phenoloxidase activity for up to 96 h postchallenge, as well as a
      prophenoloxidase-activating trypsin activity, were observed for L. dispar
      challenged with E. aulicae when compared to an E. maimaiga challenge. Three
      isoforms of phenoloxidase (pI 5.0-5.5) and at least six isoforms of trypsin
      activity (four basic trypsins pI 8-10 and two acidic trypsins pI 4-6) with
      preferences for small amino acid residues were activated in L. dispar after
      challenge. In vitro prophenoloxidase activation experiments showed that treatment
      of L. dispar hemolymph with E. aulicae protoplast plasma membranes consistently
      resulted in higher prophenoloxidase activation than E. maimaiga. We suggest that
      differences in protoplastic components of Entomophaga species, such as the
      surface glycoproteins, are implicated in activation of zymogenic trypsins in the
      insect which in turn activate the prophenoloxidase cascade as a nonpermissive
      response. Copyright 1998 Academic Press.

PMID- 9784346
TI  - Structural and ultrastructural changes during the infection of UFL-AG-286 cells
      with the baculovirus AgMNPV
AB  - During infection of the permissive insect cell line UFL-AG-286 by the baculovirus
      Anticarsia gemmatalis nucleopolyhedrovirus (AgMNPV-2D) several morphological
      changes occur. By 12 h postinfection (h p.i.), the infected cells became round
      and exhibited a decrease in the number of cytoplasmic projections. By 24 h p.i.,
      it was possible to detect a virogenic stroma inside the cell nucleus, and after
      48 h p.i., polyhedral inclusion bodies were observed. Some of these morphological
      modifications are probably due to changes in the cytoskeleton of the cell and
      this possibility was substantiated by the observation that the distribution of
      actin and microtubules was dramatically modified upon infection. Several viral
      induced proteins were also produced during infection and a sharp decrease in
      overall protein synthesis was observed. These results are very similar to those
      obtained with other cell lines infected with different baculoviruses, indicating
      a similar mechanism of infection. Copyright 1998 Academic Press.

PMID- 9784347
TI  - Modeling and biological implication of time-dose-mortality data for the
      entomophthoralean fungus, zoophthora anhuiensis, on the green peach aphid myzus
      persicae
AB  - The entomophthoralean fungus Zoophthora anhuiensis frequently causes epizootics
      in populations of the green peach aphid, Myzus persicae, infesting cruciferous
      crops in the middle and lower regions of the Changjiang River, China, during late
      autumn and early winter. In this study, a bioassay was conducted by exposing
      aphids on detached leaves to varying doses of Z. anhuiensis conidia discharged
      from in vitro cultures. Ten doses (1.5-198 conidia/mm2) were used, with each dose
      including 64-120 aphids. The aphids were maintained at 18 degreesC under a
      photophase of 12:12 (L:D) and observed daily for mortality. The resulting time
      dose-mortality data fitted well to a conditional mortality probability model
      based on the Hosmer-Lemeshow test (C = 9.52, df = 8, P = 0.70), resulting in a
      cumulative mortality probability model. The parameters from the latter model were
      used to estimate the lethal dose (LD50) and time (LT50) for the fungal species
      against the pest. The LD50 values were 87, 44, and 34 conidia/mm2 on days 5, 6,
      and 7 after exposure, respectively. The estimates of the LT50 values decreased
      from 6.7 days at 37 conidia/mm2 to 4.5 days at 198 conidia/mm2. The results
      indicate that Z. anhuiensis could be a promising aphid pathogen for microbial
      control competitive with other Zoophthora species. The model is recommended for
      use in the analysis of time-dose-mortality data for fungus-insect associations.
      The biological implications of the parameters and the advantages of the modeling
      technique over the conventional method of probit analysis are discussed.
      Copyright 1998 Academic Press.

PMID- 9784348
TI  - Cloning and sequencing of cDNA of the insecticidal toxin hirsutellin A
AB  - The hyphomycete Hirsutella thompsonii produces an extracellular insecticidal
      protein, Hirsutellin A. This basic protein, cytolytic against insect cells and
      capable of inhibiting protein translation, possesses biological features similar
      to the well-characterized ribosomal-inhibiting proteins (RIPs) alpha-sarcin,
      mitogellin, and restrictocin. Cloning and DNA sequencing analysis of the 3' and
      5' RACE products of HtA cDNA identifies a consensus DNA sequence which
      encompasses the complete open reading frame of the HtA gene. This gene codes for
      a precursor of 164 aa which includes a 34-aa leader sequence. The leader sequence
      of HtA, like those found in RIPs, contains a signal and a pro sequence. The
      mature 130-aa HtA, having a calculated Mr = 14,159 and pI = 9.21, is considered a
      stable hydrophilic protein. HtA does not possess the characteristic RNase motif
      of fungal RIPs but does possess a series of consensus phosphorylation and
      myristoylation sites and a putative ATP/GTP binding site. The sequence of HtA is
      unique and does not produce the secondary or tertiary structures characteristic
      of other fungal RIPs. Copyright 1998 Academic Press.

PMID- 9784349
TI  - Effects of bacillus thuringiensis and destruxins (Metarhizium anisopliae
      mycotoxins) combinations on spruce budworm (Lepidoptera: tortricidae)
AB  - Laboratory bioassays were performed in order to assess the efficacy of a
      combination of a commercial preparation of Bacillus thuringiensis var. kurstaki
      (B.t.k.) (Thuricide) with destruxins (Metarhizium anisopliae mycotoxins) on the
      fifth instar of Choristoneura fumiferana Clemens. Lethal doses were determined
      for each microbial agent and used as a basis for the bioassays involving a
      combination of the two agents. Interaction or the lack of interaction was
      determined by comparing the observed and the theoretically expected mortality
      rates. Seven out of 10 different combinations demonstrated synergism between the
      two agents. The modelization applied on results allowed us to establish the
      following general equation: LDmixture = 1.259(LDDx) + 1.129(LDBt) -
      0.016(LDDx)(LDBt) + 12.196. Such an equation explains the relationship which
      exists between the two lethal agents (R2 = 0.99). Our results suggest that the
      two agents contribute to the synergism in the system and that a combination of
      both could be an efficient means of controlling C. fumiferana populations and of
      reducing the dose of B.t.k. which is usually required for such a control.
      Copyright 1998 Academic Press.

PMID- 9784350
TI  - The impact of host developmental status on baculovirus replication
AB  - The yield of progeny occlusion bodies from a baculovirus infection is a critical
      parameter governing viral population dynamics in the field. Previous evidence has
      suggested that the ability of the virus to block host development may be an
      important factor in determining yield of progeny virus. Here, we explore the
      relationship between yield, dose, and host developmental status at the time of
      infection during Autographa californica nucleopolyhedrovirus infection of final
      instar Heliothis virescens. The data indicate that occlusion body yield is
      strongly inversely dependent on the time elapsed after ecdysis before the insect
      is infected. The later in the instar the infective dose is received, the lower
      the efficiency with which the virus can block host development. The occlusion
      body yield from insects whose development is completely arrested is more than
      fourfold greater than the yield from insects that have initiated prepupal
      development. Dose is also an important factor, with high-dose infections more
      likely to lead to developmental arrest. Thus, the infection parameters that give
      rise to optimal progeny virus yield are infection at high dose early in the
      instar. Analysis of ecdysteroid titers demonstrated that only low levels of
      ecdysteroids are detectable in insects whose development is completely arrested.
      In contrast, in insects whose development was only partially arrested, extremely
      high ecdysteroid titers were frequently observed. These data support the
      hypothesis that the function of the baculovirus ecdysteroid UDP
      glucosyltransferase gene is to delay or block host development, with the benefit
      of increasing the yield of progeny virus. Copyright 1998 Academic Press.

PMID- 9784351
TI  - New cell lines from heliothis virescens: characterization and susceptibility to
      baculoviruses
AB  - New cell lines from embryos of Heliothis virescens were recently developed. Six
      primary cultures were initiated in June 1995. From these initial cultures, two
      produced sufficient cell growth to allow subcultivation and eventually led to the
      establishment of seven cell strains, three of which are maintained at low
      temperatures (17 degreesC). The strains were compared with a previously
      established cell line from H. virescens by isozyme analysis and shown to be from
      the same species. All the strains were inoculated with various baculoviruses,
      including Autographa californica nucleopolyhedrovirus (NPV), Anagrapha falcifera
      NPV, Anticarsa gemmatalis NPV, Rachoplusia ou NPV, Lymantria dispar NPV (LdMNPV),
      Orgyia pseudotsugata NPV (OpSNPV), O. leucostigma NPV (OlMNPV), and Helicoverpa
      zea NPV (HzSNPV). All seven strains were highly susceptible to the noctuid NPVs,
      and large numbers of occlusion bodies (OBs) were produced in most of the
      inoculated cells. The HzSNPV infection developed at a slower rate (requiring 1
      week or more before a substantial number of cells contained OBs compared with 2-3
      days for the other three noctuid NPVs). Three of the H. virescens strains were
      also susceptible to OpSNPV although only 10-20% of the cells produced OBs with
      this virus. We did not observe cytopathology (CPE) in any cells inoculated with
      OlMNPV or LdMNPV. Our results suggest that these new strains can be useful for
      the study and possibly the production of baculoviruses for which no effective
      cell systems are available and for comparative studies on multiple virus species.

PMID- 9784352
TI  - Routes of penetration of the entomopathogenic nematode steinernema feltiae
      attacking larval and adult houseflies (Musca domestica)
AB  - The way in which Steinernema feltiae (Nematoda: Rhabditida: Steinernematidae)
      infects the housefly, Musca domestica (Diptera: Muscidae), was investigated.
      Adult flies were confined in petri dishes containing 1 million S. feltiae on
      capillary matting and individuals were dissected at hourly intervals. First,
      second, and third instar larvae were placed on filter papers with 100,000
      infective juveniles, and then 2 larvae were examined at 30-min intervals.
      Infective juveniles were aggregated on the proboscis and anal aperture of male
      and female houseflies after 1 h. The nematodes penetrated female flies after 2 h
      by moving through the cloaca, then along the oviduct, and through the ovaries.
      Male houseflies were penetrated via the cloaca, and then S. feltiae entered the
      hemcoel by penetrating the wall of the ejaculatory sac. All larval stages were
      penetrated via the anal aperture. Nematodes then moved through the hind gut and
      penetrated the wall of the ileum, immediately posterior to the pylorus. Female
      nematodes were observed to penetrate housefly larvae before male nematodes. Male
      nematodes penetrated after 10 females had successfully parasitized a larva.
      Copyright 1998 Academic Press.

PMID- 9784353
TI  - Sex ratio and the infection process in entomopathogenic nematodes: are males the
      colonizing Sex?
AB  - In laboratory assays, male infective juveniles of some species of
      entomopathogenic nematodes in the genus Steinernema differ from females in their
      tendency to disperse and in their responses to the volatile cues emitted by
      parasitized and nonparasitized insects. These differences suggest that male
      infective juveniles might locate and establish in insect hosts before females,
      and that infection by males might render hosts suitable for nematode development
      and more attractive to females: "the male colonization hypothesis." We tested
      this hypothesis in laboratory experiments in which larvae of the greater wax
      moth, Galleria mellonella (L.), were exposed to infective juveniles of S. glaseri
      (Steiner) (NC strain) in sand columns for various periods of time. The hosts were
      dissected to determine the sex ratio of the adult nematodes that became
      established. We found that infective juveniles entered hosts over periods of up
      to at least 14 h, and that sex ratios varied among experiments. However, there
      were no temporal differences in colonization by males and females during the
      infection process: the proportion of males in host cadavers was not related to
      exposure time or to the total number of nematodes in host cadavers. This result
      is inconsistent with the male colonization hypothesis. We conclude that
      differential colonization of hosts over time by males and females either does not
      occur in S. glaseri, or occurs only rarely or under conditions differing from
      ours, or occurs to such a small extent that it is difficult to detect. In S.
      glaseri, male infective juveniles tend to emerge from host cadavers before
      females. This might give males an advantage over females in locating new hosts
      following a natural emergence. Nonetheless, to date, males have not been shown to
      colonize hosts before females in any steinernematid species. Copyright 1998
      Academic Press.

PMID- 9784354
TI  - Antimicrobial activity of exocrine glandular secretions, hemolymph, and larval
      regurgitate of the mustard leaf beetle phaedon cochleariae
AB  - Larvae and adults of the mustard leaf beetle Phaedon cochleariae (Coleoptera:
      Chrysomelidae) possess exocrine glands with secretions which are used in defense
      against predators. This study addressed the question whether these defensive
      secretions also display antimicrobial activity. Additionally, the effects of
      larval and adult hemolymph and larval regurgitate toward microorganisms were
      examined. The larval glandular secretion showed growth-inhibitory activity
      against the gram-negative bacterium Escherichia coli, but no lytic effect against
      cell walls of the gram-positive bacterium Micrococcus luteus. Growth of the yeast
      Saccharomyces cerevisiae and of the entomopathogenic fungus Beauveria bassiana
      was also inhibited by the larval secretion. The antibacterial and antifungal
      activity of the larval secretion was found to be due to its main component, the
      iridoid monoterpene, (epi)chrysomelidial. The mechanism of its antifungal
      activity was examined by different bioassays and compared to the commercially
      available fungicide nystatin. The antifungal activity of the larval secretion is
      not due to a loss of intracellular potassium in treated fungal cells, while high
      potassium efflux from treated cells is the mode of action of common fungicides.
      The larval secretion exhibited direct cytotoxicity against both fungal cells and
      plasmatocytes isolated from the greater wax moth Galleria mellonella. In contrast
      to the larval secretion, the adult glandular secretion of P. cochleariae showed
      lytic activity against the cell walls of the gram-positive bacterium M. luteus,
      but no activity against the gram-negative bacterium E. coli and eukaryotic cells.
      Hemolymph and larval regurgitate of P. cochleariae displayed the same activity as
      the tested glandular secretion of adults. Copyright 1998 Academic Press.

PMID- 9784355
TI  - Seasonal variation and effects of age, food availability, size, gonadal
      development, and parasitism on the hemogram of mytilus galloprovincialis
AB  - The study of hemogram characteristics in a population of cultured mussels through
      a period of 18 months revealed that the concentration of circulating Mytilus
      galloprovincialis hemocytes varied, following a seasonal pattern, being
      positively correlated with water temperature. Most mussels had between 1 and 5 x
      10(6) hemocytes/ml of hemolymph. Differential counts showed that M.
      galloprovincialis hemolymph contained more granulocytes than hyalinocytes. The
      hemolymph cell concentration was not associated with size or weight of mussels.
      Circulating hemocyte concentration did not decrease in mussels with reabsorbing
      gonad, despite the hemocytic accumulation inside and around gonad follicles. No
      significant difference in hemolymph cell concentration was found between two
      groups of mussels of different ages. Nevertheless, older mussels had higher mean
      values of circulating granulocytes although these differences were only
      significant in the winter sample. Infestation by the protistan Marteilia
      refringens caused a significant increase of hemocytes in the hemolymph. In
      addition, the occurrence of some parasites induced significant changes in the
      proportion of circulating hemocyte types. Results suggested that a hemocytic
      response was detected in hemolymph when the foreign organisms are pathogenic and
      evoke a heavy inflammatory reaction. Mussels with large or numerous
      granulocytomas had a higher number of circulating granulocytes and hyalinocytes
      than those without granulocytomas. Copyright 1998 Academic Press.

PMID- 9784356
TI  - Host and penetration site location by entomopathogenic nematodes against japanese
      beetle larvae
AB  - Entomopathogenic nematodes are soil-inhabiting parasites of insects. Behavioral
      responses to host and host environmental cues are critical steps in the infection
      process for some nematode species, such as Steinernema glaseri and
      Heterorhabditis bacteriophora, of finding, recognizing, and penetrating insects.
      We investigated the impact of host and host environmental cues on the infectivity
      of these two nematodes by testing their response to whole and wounded grass roots
      and gut fluid and hemolymph of Popillia japanica larvae. We also compared the
      influence of root presence on infectivity. Infective juveniles of both nematode
      species migrated to whole and wounded grass roots, suggesting that these
      nematodes may use cues from grass roots and root wounds for host habitat finding.
      Root presence enhanced the infectivity of S. glaseri, presumably because feeding
      larvae ingest more nematodes than nonfeeding ones. However, the infectivity of H.
      bacteriophora was not enhanced by grub feeding. This may due to the weak gut
      penetration ability of this species. We conclude that the two species respond
      similarly to host and host environmental cues but achieve infection differently
      via penetration: S. glaseri possesses superior gut penetration ability, whereas
      intersegmental areas such as leg and maxilla joints serve as cuticle penetration
      sites for H. bacteriophora. Copyright 1998 Academic Press.

PMID- 9784357
TI  - Toxicity of purified fungal toxin hirsutellin A to the citrus rust mite
      phyllocoptruta oleivora (Ash.)
AB  - A toxic protein, hirsutellin A, isolated from culture filtrate during liquid
      fermentation of the fungal mycelia of Hirsutella thompsonii, was tested using
      contact/residual and residual leaf bioassay methodologies at concentrations of 0,
      10, 32, 56, and 100 &mgr;g/ml against adult citrus rust mite, Phyllocoptruta
      oleivora. P. oleivora is the natural host of the parasitic fungus, H. thompsonii.
      Mite mortality increased with an increase in hirsutellin A concentration,
      reaching virtually 100% at 100 &mgr;g/ml using both leaf assay methods. The
      number of eggs found on leaf disk bioassays within a 3-day period decreased
      significantly with an increase in hirsutellin A concentration, suggesting that
      fecundity was affected prior to the death of the host. Copyright 1998 Academic
      Press.

PMID- 9784358
TI  - Timing of an early sporulation sequence of microsporidia in the genus vairimorpha
      (Microsporidia: burenellidae)
AB  - An early sporulation event in the host midgut tissues has been reported for
      several species of microsporidia infecting Diptera, Hymenoptera, and Lepidoptera.
      The role of these primary spores, formed between 35 and 96 h postinfection per
      os, has been suggested to be the cell to cell spread of infection within the
      host, but the sequence of events during the early sporulation stages has been
      reported for only a few species of microsporidia. We investigated these early
      life cycle events for two species of microsporidia, Vairimorpha necatrix and
      Vairimorpha sp. from Lymantria dispar, tested in the laboratory hosts Spodoptera
      exigua and L. dispar, respectively. We injected hemolymph drawn from orally
      infected host larvae into uninfected larvae at time periods from 2 to 96 h
      postinfection to determine the timing of infection of the hemolymph and target
      tissues. Our studies demonstrated that, for both Vairimorpha species, the early
      sporulation in the midgut tissues is a discrete first stage of infection.
      Invasion of the hemolymph and infection of the target tissues follows maturation
      of "primary spores" in the midgut and coincides with the germination of these
      spores beginning approximately 30 h postinfection for hosts held at a constant 24
      degreesC. The developmental stages of the microsporidia observed in the target
      tissues at specific time periods postinfection corresponded to the stages
      observed in the hemocytes, suggesting that sporoplasms from the germinating
      primary spores are directly injected into the target tissues and the hemolymph.
      Copyright 1998 Academic Press.

PMID- 9784359
TI  - Horizontal transmission of amblyospora dolosi (Microsporidia: amblyosporidae) to
      the copepod metacyclops mendocinus (Wierzejski, 1892)
AB  - This study documents the involvement of a copepod intermediate host in the life
      cycle of Amblyospora dolosi from the neotropical mosquito Culex dolosus in
      Argentina. Meiospores of A. dolosi from the mosquito host were infectious per os
      to female adults of the copepod Metacyclops mendocinus. All developmental stages
      in the copepod were haplophasic (unpaired nuclei), with sporulation producing a
      second type of uninucleate spore. These spores, formed in the ovaries of M.
      mendocinus, were lanceolate, curved, and measured 14.3 x 3.8 &mgr;m. This study
      supports previous life cycle studies which demonstrate that most if not all
      Amblyospora spp. in mosquitoes require an obligate intermediate copepod host to
      complete the life cycle.

PMID- 9784360
TI  - Efficacy of lepidopteran specific delta-endotoxins of bacillus thuringiensis
      against helicoverpa armigera

PMID- 9784361
TI  - The response time of insect larvae infected with recombinant baculoviruses

PMID- 9784362
TI  - Notice

PMID- 9784363
TI  - Infectious human papillomavirus type 18 pseudovirions.
AB  - Human papillomavirus type 18 (HPV18) capsid proteins L1 and L2, synthesised in
      mammalian cells using recombinant vaccinia viral expression vectors, are
      transported to the nucleus and assembled into virus-like particles. When 293T
      cells, which express SV40 T antigen, were transfected with plasmid DNAs
      containing an SV40 origin of replication then infected with vaccinia viral
      vectors encoding L1 and L2, plasmid DNA was encapsidated into the particles. The
      DNAs ranged in size from 5.4 to 7.9 kb. By encapsidating plasmids containing
      either the beta-galactosidase gene or the puromycin-resistance gene, the
      pseudovirions were shown to be infectious in that they could transfer beta
      galactosidase activity or confer resistance to puromycin to a number of cell
      types, indicating that the uptake and decapsidation of HPV particles are not the
      main determinants of cell type specificity of HPV. Episomal HPV16 DNA in a
      cervical keratinocyte line could also be encapsidated. Further investigation
      showed that DNA encapsidation is independent of HPV DNA sequences and of T
      antigen-mediated plasmid DNA replication. Instead, the minor capsid protein, L2,
      was found to be attached to plasmid mini-chromosomes extracted from these cells,
      suggesting a role for L2 in encapsidation. Consistent with this, the L1 protein
      alone was unable to encapsidate DNA, although it was able to form virus-like
      particles. The results suggest that intracellular episomal DNAs of suitable size
      can be encapsidated by the HPV18 L1 and L2 proteins without the need of any HPV
      packaging signal, and reintroduced into cells.

PMID- 9784364
TI  - Binding of the fur (ferric uptake regulator) repressor of Escherichia coli to
      arrays of the GATAAT sequence.
AB  - The mode of DNA binding of the Fur (ferric uptake regulator) repressor which
      controls transcription of iron-responsive genes in Escherichia coli, has been re
      examined. Using as a reference the known sites at the promoter of the aerobactin
      operon of Escherichia coli, we have compared in detail the patterns of
      interaction between the purified Fur protein and natural or synthetic DNA
      targets. DNase I and hydroxyl radical footprinting, as well as missing-T assays,
      consistently revealed that functional Fur sites are composed of a minimum of
      three repeats of the hexameric motif GATAAT rather than by a palindromic 19 bp
      target sequence. Extended binding sites, constructed by stepwise addition of one
      or two direct repeats of the same sequence, were occupied co-operatively by Fur
      with the same pattern of interactions as those observed with the core of three
      repeats. This indicated that functional sites with a range of affinities can be
      formed by the addition of discrete GATAAT extensions to a minimal recognition
      sequence. The fashion in which Fur binds its target, virtually unknown in
      prokaryotic transcriptional regulators, accounts for the observed helical
      wrapping of the protein around the DNA helix.

PMID- 9784365
TI  - Transcription initiation and RNA processing in the mitochondria of the red alga
      Chondrus crispus: convergence in the evolution of transcription mechanisms in
      mitochondria.
AB  - The mitochondrial DNA (mt DNA) of the red alga Chondrus crispus is shown to be
      transcribed into two large RNA molecules. These primary transcripts are cleaved
      once, at the level of a tRNA, then the resulting products are processed via
      multiple maturation events into either mono- or poly-cistronic RNAs. Transcripts
      were detected for all genes and open reading frames, except for rps11 and orf172.
      For both transcription units the initiation of transcription was mapped by in
      vitro RNA capping and primer extension experiments within inverse repeated
      sequences at the north pole of the molecule. Consistent with primer extension
      mapping, putative promoter motifs sharing significant similarities with both
      chicken and Xenopus mitochondrial promoters were found in the C. crispus
      mitochondrial genome. Altogether C. crispus mitochondrial DNA appears to be
      transcribed as animal mtDNA is, suggesting that transcription mechanisms in
      mitochondria are dependent on the overall organization of the mitochondrial
      genome irrespective of the eukaryotic phylogeny.

PMID- 9784366
TI  - Binding of phage phi29 protein p4 to the early A2c promoter: recruitment of a
      repressor by the RNA polymerase.
AB  - Regulatory protein p4 from Bacillus subtilis phage Phi29 represses the early A2c
      promoter by binding upstream from RNA polymerase and interacting with the C
      terminal domain of the RNA polymerase alpha subunit. This interaction stabilizes
      the RNA polymerase at the promoter in such a way that promoter clearance is
      prevented. Here, the binding of protein p4 to the A2c promoter has been studied.
      In the absence of RNA polymerase, protein p4 was found to bind with low affinity
      to a site centered at position -39 relative to the transcription start site. When
      RNA polymerase was present, protein p4 was displaced from this site and bound
      instead to a different target centered at position -71. Stable binding to this
      site requires the interaction of protein p4 with the C-terminal domain of the RNA
      polymerase alpha-subunit. Both sites contain sequences resembling the well
      characterized p4 binding site present at the late A3 promoter, to which p4 binds
      with high affinity. A mutational analysis revealed that the site at -71 is
      critical for a stable interaction between protein p4 and RNA polymerase, and for
      efficient repression, whereas mutation of the site at -39 had only a small effect
      on repression efficiency. Therefore, RNA polymerase plays an active role in the
      repression mechanism by stabilizing the repressor at the promoter, generating a
      nucleoprotein complex that is too stable to allow promoter clearance.

PMID- 9784367
TI  - A common motif organizes the structure of multi-helix loops in 16 S and 23 S
      ribosomal RNAs.
AB  - Phylogenetic and chemical probing data indicate that a modular RNA motif, common
      to loop E of eucaryotic 5 S ribosomal RNA (rRNA) and the alpha-sarcin/ricin loop
      of 23 S rRNA, organizes the structure of multi-helix loops in 16 S and 23 S
      ribosomal RNAs. The motif occurs in the 3' domain of 16 S rRNA at positions 1345
      1350/1372-1376 (Escherichia coli numbering), within the three-way junction loop,
      which binds ribosomal protein S7, and which contains nucleotides that help to
      form the binding site for P-site tRNA in the ribosome. The motif also helps to
      structure a three-way junction within domain I of 23 S, which contains many
      universally conserved bases and which lies close in the primary and secondary
      structure to the binding site of r-protein L24. Several other highly conserved
      hairpin, internal, and multi-helix loops in 16 S and 23 S rRNA contain the motif,
      including the core junction loop of 23 S and helix 27 in the core of 16 S rRNA.
      Sequence conservation and range of variation in bacteria, archaea, and eucaryotes
      as well as chemical probing and cross-linking data, provide support for the
      recurrent and autonomous existence of the motif in ribosomal RNAs. Besides its
      presence in the hairpin ribozyme, the loop E motif is also apparent in helix P10
      of bacterial RNase P, in domain P7 of one sub-group of group I introns, and in
      domain 3 of one subgroup of group II introns.

PMID- 9784368
TI  - A branched stem-loop structure in the M-site of bacteriophage Qbeta RNA is
      important for template recognition by Qbeta replicase holoenzyme.
AB  - An internal site on bacteriophage Qbeta RNA, the M-site (map position 2545 to
      2867), was recently shown by us to be required for the efficient initiation of
      minus strand synthesis by Qbeta replicase. In a more detailed mutational
      analysis, we show here that the essential elements within the M-site consist of
      two successive stem-loop structures followed by a bulge loop of unpaired purines,
      located at nucleotides 2696 to 2754 on the tip of a long, imperfectly base-paired
      stalk. Mutational changes affecting the sequences of paired or unpaired
      nucleotides in this segment reduced the template efficiency only mildly. The only
      severe effects were observed when one of the helical stems or the unpaired bulge
      was completely deleted or substantially shortened. We conclude that the three
      dimensional backbone arrangement of these three elements constitutes the feature
      recognized by replicase. The role of the long stalk remains undetermined, because
      mutations that either stabilized or disrupted its base-pairing barely affected
      template activity, and even deletion of a major portion of one of its strands did
      not cause complete inactivation. Earlier evidence had implicated protein S1 (the
      alpha subunit of replicase) as the mediator of the M-site interaction. The lack
      of an active M-site on the Qbeta RNA template has the same quantitative and
      qualitative effects on template recognition as the absence of the S1 protein from
      replicase in the presence of wild-type RNA. We therefore believe that the M-site
      interaction explains most of the role of S1 protein in the replication of Qbeta
      RNA by replicase.

PMID- 9784369
TI  - Plasmid pIP501 encoded transcriptional repressor CopR binds to its target DNA as
      a dimer.
AB  - The CopR protein is one of the two regulators of pIP501 copy number. It acts as
      transcriptional repressor at the essential repR promoter pII. Previously, we
      found that CopR contacts two consecutive major grooves (site I and site II) on
      the same face of the DNA. In spite of identical sequence motifs in these sites,
      neighboring bases were contacted differently. Furthermore, we showed that CopR
      can dimerize in solution. We demonstrate by two independent methods that CopR
      binds the DNA as a dimer. We present data that suggest that the sigmoidal CopR
      DNA binding curve published previously is the result of two coupled equilibria:
      dimerization of CopR monomers and CopR dimer-DNA binding. A KD-value of 1.44(+/
      0.49)x10(-6) M for CopR dimers was determined by analytical ultracentrifugation.
      Based on this value and the binding curve, the equilibrium dissociation constant
      K2 for the CopR-DNA complex was calculated to be 4(+/-1. 3)x10(-10) M.
      Quantitative Western blot analysis was used to determine the intracellular
      concentration of CopR in Bacillus subtilis. This value, 20x10(-6) to 30x10(-6) M,
      is 10 to 20-fold higher than the equilibrium constant for dimer dissociation,
      suggesting that CopR binds in vivo as a preformed dimer.

PMID- 9784370
TI  - In vitro selection of RNAs aminoacylated by Escherichia coli leucyl-tRNA
      synthetase.
AB  - To investigate systematically the RNA sequences necessary for aminoacylation by
      Escherichia coli leucyl-tRNA synthetase, RNAs with leucylation activity were
      isolated by in vitro selection from a library of tRNALeu variants possessing
      randomized sequences in the D-loop, the variable arm, and the T-loop. After two
      rounds of selection, most of the selected variants showed the following features:
      (1) the tertiary interaction between nucleotides at positions 15 and 48 was A15
      U48; (2) the continuous G18G19 sequence, which is invariant in canonical tRNAs,
      appeared at the fixed position in the D-loop; and (3) the nucleotide at position
      20a in the D-loop was A. These selected nucleotides and their positions,
      concentrating on the hinge region of tRNA, were identical to those of native
      tRNALeu. In contrast, although the long variable arm is the most characteristic
      of the tRNALeu structure, the primary and secondary structures were not
      correlated with the leucylation activity. These findings indicate that A15-U48,
      A20a, and G18G19 located at specific positions are involved in the tertiary
      folding of leucine-accepting tRNA molecules. With increases in the selection
      cycle, the D-loop sequence and the secondary structure of the variable arm became
      similar to those of tRNALeu, suggesting that tRNALeu represents an optimized RNA
      sequence for leucylation.

PMID- 9784371
TI  - Assemblies of replication initiator protein on symmetric and asymmetric DNA
      sequences depend on multiple protein oligomerization surfaces.
AB  - The pi35.0 protein of plasmid R6K regulates transcription and replication by
      binding a DNA sequence motif (TGAGR) arranged either asymmetrically into 22 bp
      direct repeats (DRs) in the gamma origin, or symmetrically into inverted half
      repeats (IRs) in the operator of its own gene, pir. The binding patterns of the
      two natural forms of the pi protein and their heterodimers revealed that the
      predominant species, pi35.0 (35.0 kDa), can bind to a single copy of the DR as
      either a monomer or a dimer while pi30.5 (30.5 kDa) binds only as a dimer. We
      demonstrate that only one subunit of a pi35.0 dimer makes specific contact with
      DNA. Electron microscopic (EM) analysis of the nucleoprotein complexes formed by
      pi35.0 and DNA fragments containing all seven DRs revealed coupled ("hand
      cuffed") DNA molecules that are aligned in a parallel orientation. Antiparallel
      orientations of the DNA were not observed. Thus, hand-cuffing depends on a highly
      ordered oligomerization of pi35.0 in such structures. The pi protein (pi35.0,
      pi30.5) binds to an IR as a dimer or heterodimer but not as a monomer. Moreover,
      a single amino acid residue substitution, F200S (pir200), introduced into pi30.5
      severely destabilizes dimers of this protein in solution and concomitantly
      prevents binding of this protein to the IR. This mutation also changes the
      stability of pi35.0 dimers but it does not change the ability of pi35.0 to bind
      IRs. To explain these observations we propose that the diverse interactions of pi
      variants with DNA are controlled by multiple surfaces for protein
      oligomerization.

PMID- 9784372
TI  - Role of the first aspartate residue of the "YxDTDS" motif of phi29 DNA polymerase
      as a metal ligand during both TP-primed and DNA-primed DNA synthesis.
AB  - Almost all known nucleic acid polymerases require three acidic residues to bind
      the metal ion during catalysis of nucleotide incorporation. Nevertheless, recent
      crystallographic data on bacteriophage RB69 DNA polymerase indicate that the
      first aspartate residue belonging to the conserved motif "YxDTDS" could have a
      merely structural role. To address this question, a mutant protein at the
      homologous aspartate residue (Asp456) in phi29 DNA polymerase was made 3'-5'
      exonuclease deficient. This allowed us to analyse the functional importance of
      this residue in different metal-dependent reactions that can be performed using
      either terminal protein (TP) or DNA primers. When Mg2+ was used as the metal
      activator, the synthetic activities of the mutant phi29 DNA polymerase, TP-primed
      initiation and DNA-primed polymerisation, were about 50-fold less efficient than
      those of the wild-type enzyme. Interestingly, the use of Mn2+ as the metal
      activator partially restored the wild-type phenotype. When polymerisation
      required an efficient translocation along the template, mutation of Asp456
      strongly affected the catalytic efficiency of phi29 DNA polymerase. The results
      presented here indicate that Asp456 has a catalytic role as a metal-activator
      ligand, but also contributes to enzyme translocation along the DNA, required
      during consecutive nucleotide incorporation cycles. Moreover, Asp456 appears to
      be critical to remodel the active site during transition from TP priming to DNA
      priming. The results are discussed in the light of structural information
      corresponding to distantly related polymerases.

PMID- 9784374
TI  - Crystal structures of acutolysin A, a three-disulfide hemorrhagic zinc
      metalloproteinase from the snake venom of Agkistrodon acutus.
AB  - Acutolysin A alias AaHI, a 22 kDa hemorrhagic toxin isolated from the snake venom
      of Agkistrodon acutus, is a member of the adamalysin subfamily of the metzincin
      family and is a snake venom zinc metalloproteinase possessing only one catalytic
      domain. Acutolysin A was found to have a high-activity and a low-activity under
      weakly alkaline and acidic conditions, respectively. With the adamalysin II
      structure as the initial trial-and-error model, the crystal structures were
      solved to the final crystallographic R-factors of 0. 168 and 0.171, against the
      diffraction data of crystals grown under pH 5.0 and pH 7.5 conditions to 1.9 A
      and 1.95 A resolution, respectively. One zinc ion, binding in the active-site,
      one structural calcium ion and some water molecules were localized in both of the
      structures. The catalytic zinc ion is coordinated in a tetrahedral manner with
      one catalytic water molecule anchoring to an intermediate glutamic acid residue
      (Glu143) and three imidazole Nepsilon2 atoms of His142, His146 and His152 in the
      highly conserved sequence H142E143XXH146XXGXXH152. There are two new disulfide
      bridges (Cys157-Cys181 and Cys159-Cys164) in acutolysin A in addition to the
      highly conserved disulfide bridge Cys117-Cys197. The calcium ion occurs on the
      molecular surface. The superposition showed that there was no significant
      conformational changes between the two structures except for a few slight changes
      of some flexible residue side-chains on the molecular surface, terminal residues
      and the active-site cleft. The average contact distance between the catalytic
      water molecule and oxygen atoms of the Glu143 carboxylate group in the weakly
      alkaline structure was also found to be closer than that in the weakly acidic
      structure. By comparing the available structural information of the members of
      the adamalysin subfamily, it seems that, when lowering the pH value, the
      polarization capability of the Glu143 carboxylate group to the catalytic water
      molecule become weaker, which might be the structural reason why the snake venom
      metalloproteinases are inactive or have a low activity under acidic conditions.

PMID- 9784373
TI  - Comparative structural analysis by [1H,31P]-NMR and restrained molecular dynamics
      of two DNA hairpins from a strong DNA topoisomerase II cleavage site.
AB  - The structural analysis of two single-stranded DNAs d(AGCTTATCATCGATAAGCT) (ATC
      19) and d(AGCTTATCGATGATAAGCT) (GAT-19) was performed by NMR and restrained
      molecular dynamics. These oligonucleotides reproduce the 15-33 segment of phage
      pBR322 DNA, which contains a strong cleavage site for topoisomerase II coupled to
      the antitumor drugs VP-16 and ellipticine. Because of their partial palindromic
      nature, the two oligonucleotides ATC-19 and GAT-19 may fold back into stable
      hairpin structures, consisting of a stem of eight base-pairs and a loop of three
      residues. NMR assignments and conformational parameters were determined from
      combined 2D NOESY, COSY and 1H-31P spectra. Conformations of ATC-19 and GAT-19
      hairpins were calculated using the X-PLOR 3.1 program. Structures were generated
      through simulated annealing procedures starting from 50 structures with
      randomized torsion angles. A good convergence was observed for ATC-19 molecules,
      while no consensus was found for GAT-19. Within the GAT-19 loop, the base
      stacking was poor and no hydrogen bond could be detected. In contrast, ATC-19
      displayed a well-defined three residue loop stabilized by both extensive base
      stackings and hydrogen bonding between the N3 atom of the adenine ring and the
      amino group of the cytosine ring. The results confirm our earlier ATC-19
      structure obtained by a completely different calculation procedure (JUMNA) and
      the higher thermal stability of ATC-19 compared to GAT-19. Moreover, due to its
      mismatched base-pair, the ATC-19 loop may be better described as a single residue
      loop rather than a three residue loop. Comparison of this loop to those
      containing sheared purine.purine base-pairs revealed striking resemblances,
      particularly on the backbone angle combination. Finally, the differences observed
      between the ATC-19 and GAT-19 structures could help toward understanding the
      sequential cleavage of DNA strands by topoisomerase II.

PMID- 9784375
TI  - A pulse-chase-competition experiment to determine if a folding intermediate is on
      or off-pathway: application to ribonuclease A.
AB  - A modified pulse-chase experiment is applied to determine if the native-like
      intermediate IN of ribonuclease A is on or off-pathway. The 1H label retained in
      the native protein is compared when separate samples of 1H-labeled IN and
      unfolded protein are allowed to fold to native in identical conditions. The
      solvent is 2H2O and the pH* is such that the unfolded protein rapidly exchanges
      its peptide NH protons with solvent, and IN does not. If IN is on-pathway, more
      1H-label will be retained in the test sample starting with IN than in the control
      sample starting with unfolded protein. The results show that IN is a productive
      (on-pathway) intermediate. Application of the modified pulse-chase experiment to
      the study of rapidly formed folding intermediates may be possible when a rapid
      mixing device is used.

PMID- 9784376
TI  - Oligomerization and divalent ion binding properties of the S100P protein: a
      Ca2+/Mg2+-switch model.
AB  - S100P is a 95 amino acid residue protein which belongs to the S100 family of
      proteins containing two putative EF-hand Ca2+-binding motifs. In order to
      characterize conformational properties of S100P in the presence and absence of
      divalent cations (Ca2+, Mg2+ and Zn2+) in solution, we have analyzed hydrodynamic
      and spectroscopic characteristics of wild-type and several variants (Y18F, Y88F
      and C85S) of S100P using equilibrium centrifugation, gel-filtration
      chromatography, circular dichroism and fluorescence spectroscopies. Analysis of
      the experimental data shows the following. (1) In agreement with the predictions
      there are two Ca2+-binding sites in the S100P molecule with different affinity;
      the high affinity binding site has an apparent binding constant of approximately
      10(7) M-1 and the low affinity binding site has an apparent binding constant of
      approximately 10(4) M-1. (2) The high and low affinity Ca2+-binding sites are
      located in the C and N-terminal parts of the S100P molecule, respectively. (3)
      These C and N-terminal sites can also bind other divalent ions. The C-terminal
      site binds Zn2+ (with relatively low affinity approximately 10(3) M-1), but not
      Mg2+. The N-terminal site binds Mg2+ with the apparent binding constant
      approximately 10(2) M-1. (4) Binding of Ca2+ to the C-terminal site and binding
      of Mg2+ to the N-terminal site occur in the physiological concentration range of
      these ions (micromolar for Ca2+ and millimolar for Mg2+). (5) Oligomerization
      state of the S100P molecule appears to change upon addition of Ca2+. On the basis
      of these observations a plausible model for S100P as a Ca2+/Mg2+ switch has been
      proposed.

PMID- 9784377
TI  - Allosteric regulation in Pseudomonas aeruginosa catabolic ornithine
      carbamoyltransferase revisited: association of concerted homotropic cooperative
      interactions and local heterotropic effects.
AB  - The allosteric catabolic ornithine carbamoyltransferase (OTCase) from Pseudomonas
      aeruginosa, a dodecamer build up of four trimers of identical subunits, shows
      strong carbamoylphosphate homotropic co-operativity. Its activity is
      allosterically inhibited by spermidine and activated by AMP. Modified forms of
      the enzyme exhibiting substantial alterations in both homotropic and heterotropic
      interactions were recently obtained. We report here the first detailed kinetic
      characterization of homotropic and heterotropic modulations in allosteric wild
      type and in engineered OTCases. Homotropic co-operativity for the saturation
      either by citrulline or arsenate was also observed when arsenate was utilised as
      an alternate substrate of the reverse reaction. Amino acid substitution of
      glutamate 105 by a glycine produces an enzyme devoid of homotropic interactions
      between the catalytic sites for carbamoylphosphate. This mutant, which is blocked
      in an active conformation, is still sensitive to the allosteric effector AMP,
      which increases affinity with respect to the substrate, carbamoylphosphate. It is
      also observed that homotropic co-operative interactions do not reappear in the
      E105G enzyme upon strong inhibition by the allosteric inhibitor of the wild-type
      enzyme, spermidine.Replacement of residues 34 to 101 of the native enzyme by the
      homologous amino acids of anabolic Escherichia coli OTCase produces a trimeric
      enzyme which retains reduced homotropic co-operativity. Activation by AMP and
      inhibition by spermidine of this chimaeric OTCase do not affect
      carbamoylphosphate homotropic co-operativity. AMP acts by reducing the
      concentration of substrate at half maximum velocity while spermidine acts in the
      inverse way. These observations indicate that in the two mutant forms of OTCase,
      homotropic and heterotropic interactions can be uncoupled and therefore must
      involve different molecular mechanisms. Furthermore, the results of stimulation
      of enzyme activity by phosphate, arsenate, pyrophosphate and phosphonoacetyl-l
      ornithine on wild-type and mutant OTCases suggest that the physiological
      substrate phosphate, besides acting at the catalytic site, may act at an
      allosteric site. On the other hand, pyrophosphate and phosphonoacetyl-l-ornithine
      activation results exclusively from interactions of this effector with the active
      site residues.

PMID- 9784378
TI  - Is sperm galactosyltransferase a signaling subunit of a multimeric gamete
      receptor?

PMID- 9784379
TI  - A ribonuclease from sclerotia of the edible mushroom Pleurotus tuber-regium.
AB  - A ribonuclease with a molecular weight of 29 kDa as determined by FPLC-gel
      filtration on Superose 12 was isolated from the sclerotia of the mushroom
      Pleurotus tuber-regium using a procedure involving extraction with aqueous
      buffer, ion exchange chromatography on DEAE-cellulose, affinity chromatography on
      Affi-gel blue gel, ion exchange chromatography on CM-cellulose, and FPLC on Mono
      S. The protein was unadsorbed on DEAE-cellulose but adsorbed on Affi-gel blue gel
      and CM-cellulose. It was homodimeric, made up of two identical subunits, each
      with a molecular weight of 14.5 kDa as witnessed in sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. It exhibited potent ribonucleolytic activity
      toward Poly G. Its ribonucleolytic activity was resistant to heating at 100
      degreesC for 30 min, but was inhibited by HgCl2, ZnSO4, NiSO4, CaCl2, and
      Pb(NO3)2.

PMID- 9784380
TI  - Identification and characterization of a new gene from human chromosome 21
      between markers D21S343 and D21S268 encoding a leucine-rich protein.
AB  - We initiated the present work as part of an effort to identify and characterize
      genes from the EST2-HMG14 region from human chromosome 21 potentially responsible
      for some of the Down syndrome (DS) features. Genomic sample sequencing with
      cosmid clone A1047 located in the ETS2-HMG14 region of chromosome 21 has led to
      the identification and sequencing of a novel 1080-bp cDNA. This cDNA contains a
      potential ORF of 867 bp predicting a 288-amino-acid protein rich in leucine with
      a molecular weight of 32.8 kD. Northern blot analysis and RT-PRC indicate that
      the expression of this novel gene is high in testis and in the human leukemic T
      cell line Jurkat and lower in other tissues including all fetal tissues studied.
      We have called to this novel gene c21-LRP (chromosome 21 leucine-rich protein)
      and, because of its location in the DS-2 region, it could be a candidate for some
      of the DS anomalies. Mapping experiments have narrowed the location of the c21
      LRP gene between markers D21S343 and D21S268 from chromosome 21. Analysis of the
      c21-LRP protein predicts two transmembrane helices and detects several signatures
      and potential homologies to known proteins pointing toward several potential
      roles for this protein.

PMID- 9784381
TI  - Cloning of a new gene (FB19) within HLA class I region.
AB  - A novel gene (named FB19) has been identified within the HLA class I region at
      human chromosome 6p21.3. A 4.5-kb cDNA containing a 2820-bp open reading frame
      for a predicted protein of 940 aa was identified. No homology with known gene was
      detected at the DNA level, while the predicted protein is characterized by a
      glycine-rich region followed by a domain of 35 residues that shows high homology
      with the CAT56 gene, another gene of MHC class I. A 4. 5-kb transcript was
      detected in several tissues and cell lines, clearly indicating a wide
      distribution of expression. Once its function is defined, it could be possible to
      investigate the relationship between the FB19 gene and the several diseases
      already mapped within the HLA class I region.

PMID- 9784382
TI  - Expanded genomic organization of conserved mammalian MHC class I-related genes,
      human MR1 and its murine ortholog.
AB  - MR1 is a major histocompatibility complex (MHC) class I-related gene located
      outside the human MHC. Among several divergent class I molecules, the predicted
      MR1 molecule is closest, in the alpha1 and alpha2 domains, to the class I group
      to which the vertebrate classical class I molecules belong. We report here the
      genomic organizations of the human MR1 and mouse Mr1 genes. Both genes exhibit
      genomic structures largely similar to those of the MHC class I genes. However,
      they are highly expanded in their scale in contrast to the classical MHC class I
      genes. Inclusion of transposable elements into introns seems to partly contribute
      to these genomic structures. Several other MHC class I-related genes also show
      relatively large genomic structures. The present study extended heterogeneity in
      the genomic organization among the class I gene family by revealing a highly
      expanded structure of the human MR1 gene and its murine ortholog.

PMID- 9784383
TI  - Producer cell-dependent requirement of the Nef protein for efficient entry of HIV
      1 into cells.
AB  - A proviral nef gene mutant of human immunodeficiency virus type 1 (HIV-1) was
      evaluated for its defective early replication step. Virus stocks were prepared
      from six CD4-positive and -negative cell lines transfected with wild-type (wt) or
      the nef mutant clone and inoculated into two target CD4-positive cell lines to
      monitor the efficiency of viral entry process. The nef mutant virions produced in
      one cell line exhibited a severe defect in the entry process, although those
      produced in the other five cell lines were only slightly less efficient than the
      wt virions at entering into cells. These results have demonstrated that the HIV-1
      Nef is critical for efficient viral entry in a producer cell-dependent manner.

PMID- 9784384
TI  - Kx, a quantitatively minor protein from human erythrocytes, is palmitoylated in
      vivo.
AB  - Kx is a quantitatively minor blood group protein of human erythrocytes which is
      thought to be a membrane transporter. In the red cell membrane, Kx forms a
      complex stabilized by a disulfide bond with the Kell blood group membrane protein
      which might function as a metalloprotease. The palmitoylation status of these
      proteins was studied by incubating red cells with [3H] palmitic acid.
      Purification of the Kell-Kx complex, by immunochromatography on an immobilized
      human monoclonal antibody of Kell blood group specificity demonstrated that the
      Kx but not the Kell protein is palmitoylated. Six cysteines in Kx are predicted
      to be intracytoplasmic and might be targets for palmitoylation. Three of these
      cysteines are present in a portion of sequence which is predicted to form an
      amphipathic alpha helix. Palmitoylation of one or several of these cysteines
      might contribute to anchor the cytoplasmic portion of the Kx protein to the inner
      surface of red cell membrane.

PMID- 9784385
TI  - Cysteine nitrosylation inactivates the HIV-1 protease.
AB  - Nitric oxide (NO) may modulate the catalytic activity of cysteine-containing
      enzymes. HIV-1 protease action is modulated by the redox equilibrium of Cys67 and
      Cys95 regulatory residues. In the present study, the inhibitory effect of NO,
      released by the NO-donor (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3
      hexenamide (NOR-3), on the aspartyl HIV-1 protease action is reported. HIV-1
      protease inactivation via NO-mediated nitrosylation of Cys regulatory residue(s)
      may represent a possible mechanism for inhibition of HIV-1 replication.

PMID- 9784386
TI  - Different in vitro and in vivo activity of low Mr phosphotyrosine protein
      phosphatase on epidermal growth factor receptor.
AB  - Low Mr phosphotyrosine protein phosphatase is a cytosolic enzyme which
      dephosphorylates platelet-derived growth factor and insulin receptor in vivo,
      thus reducing cellular mitogenic response to such growth factors. Following cell
      stimulation with platelet-derived growth factor the phosphatase undergoes a
      redistribution from the citosol to the Triton X-100-insoluble fraction where its
      activity upon the growth factor receptor is intense. Previous research uncovered
      evidence that low Mr phosphotyrosine protein phosphatase dephosphorylates the
      epidermal growth factor receptor in vitro. Here we demonstrate that in vivo the
      enzyme is not active on the phosphorylated epidermal growth factor receptor and
      it does not influence the mitogenic response of cells. Since the enzyme
      distribution is not affected by epidermal growth factor stimulation, involvement
      of a recruitment mechanism in the definition of low Mr phosphotyrosine protein
      phosphatase substrate specificity is hypothesized.

PMID- 9784387
TI  - Lycopene in association with alpha-tocopherol inhibits at physiological
      concentrations proliferation of prostate carcinoma cells.
AB  - The effect of lycopene alone or in association with other antioxidants was
      studied on the growth of two different human prostate carcinoma cell lines (the
      androgen insensitive DU-145 and PC-3). It was found that lycopene alone was not a
      potent inhibitor of prostate carcinoma cell proliferation. However, the
      simultaneous addition of lycopene together with alpha-tocopherol, at
      physiological concentrations (less than 1 microM and 50 microM, respectively),
      resulted in a strong inhibitory effect of prostate carcinoma cell proliferation,
      which reached values close to 90 %. The effect of lycopene with alpha-tocopherol
      was synergistic and was not shared by beta-tocopherol, ascorbic acid and
      probucol.

PMID- 9784388
TI  - A Brugia malayi antigen specifically recognized by infected individuals.
AB  - Western blot analyses were performed on 444 serum specimens: 40 sera from
      microfilaraemic individuals, 10 sera from elephantiasis patients, 24 treated
      individuals, 50 sera from residents of endemic areas without anti-filarial IgG4
      antibodies (endemic normals), 20 sera from amicrofilaraemic individuals with high
      anti-filarial IgG4 antibodies, 200 sera from healthy city-dwellers (non-endemic
      samples), and 100 sera from soil-transmitted helminth-infected individuals. Phast
      electrophoresis system was used to electrophorese Brugia malayi soluble adult
      worm antigen on 10-15% SDS-PAGE gradient gels followed by electrophoretic
      transfer onto PVDF membranes. Membrane strips were then successively incubated
      with blocking solution, human sera, and monoclonal anti-human IgG4 antibody-HRP,
      with adequate washings done in between each incubation step. Luminol
      chemiluminescence detection was then used to develop the blots. An antigenic band
      with the MW of approximately 37 kDa was found to be consistently present in the
      Western blots of all microfilaraemic sera, all amicrofilaraemic sera with high
      titres of anti-filarial IgG4 antibodies, some treated patients, and some
      elephantiasis patients. The antigen did not occur in immunoblots of individuals
      with other helminthic infections, normal endemic individuals, and city dwellers.
      Therefore the B. malayi antigen of with the MW of approximately 37 kDa
      demonstrated specific reactions with sera of B. malayi-infected individuals and
      thus may be useful for diagnostic application.

PMID- 9784389
TI  - Ranatuerins: antimicrobial peptides isolated from the skin of the American
      bullfrog, Rana catesbeiana.
AB  - Nine peptides, termed ranatuerins 1-9, with antimicrobial activity towards
      Staphylococcus aureus, were isolated from an extract of the skin of the adult
      American bullfrog, Rana catesbeiana. In common with other cytolytic peptides from
      Ranid frogs, (e.g. ranalexin, gaegurins, brevinins), ranatuerins 1 and 4 contain
      an intramolecular disulfide bridge forming a heptapeptide ring whereas in
      ranatuerins 2 and 3 the disulfide bridge forms a hexapeptide ring. The
      structurally related ranatuerins 5-9 comprise 12 - 14 amino acids and show
      sequence similarity towards the hemolytic peptides A1 and B9 previously isolated
      from the skin of Rana esculenta. Of the peptides purified, ranatuerin 1
      (SMLSVLKNLGKVGLG FVACKINKQC) showed the broadest spectrum of antimicrobial action
      with inhibitory activity against S. aureus, Escherichia coli and Candida
      albicans.

PMID- 9784390
TI  - The requirement of yeast Ssl2 (Rad25) for the repair of cisplatin-damaged DNA.
AB  - Cisplatin is one of the most widely used anticancer agents. Cisplatin-induced
      cytotoxicity results from its ability to form cisplatin-DNA adducts within the
      cellular genome which can inhibit the transcription of genes and the replication
      of DNA. Cisplatin-adducts are primarily removed by the nucleotide excision repair
      (NER) pathway. The SSL2 (RAD25) gene of Saccharomyces cerevisiae, a homolog of
      the XPB (ERCC3) gene in humans, is involved in the nucleotide excision repair of
      UV-damaged DNA and is also required for cell viability. However, the role of Ssl2
      (Rad25) in cisplatin sensitivity has not been examined. In this study, we have
      demonstrated that a yeast strain carrying the mutant allele SSL2-XP, a truncated
      form of SSL2 (RAD25) at the carboxyl terminus to mimic the human XPB (ERCC3)
      mutation, has increased cellular sensitivity to cisplatin in comparison to wild
      type cells. Analysis by host cell reactivation (HCR) assay further shows that
      Ssl2 (Rad25) is required for the repair of cisplatin-damaged DNA.

PMID- 9784391
TI  - Identification of the nuclear factor HMG2 as an activator for DFF nuclease
      activity.
AB  - DNA fragmentation during apoptosis is mediated by a heterodimeric protein
      complex, DFF45/ICAD and DFF40/CAD/CPAN. Purified DFF40 alone possesses intrinsic
      nuclease activity that is inhibited by its association with DFF45. The
      proteolytic cleavage of DFF45 by caspase-3 frees the DFF40 subunit to function as
      a nuclease. In the course of identifying factors that stimulate DFF activity, we
      have isolated a nuclear factor and identified it as the high mobility group
      protein 2 (HMG2). We found that bacterially expressed HMG2 is able to enhance the
      nuclease activity of DFF. As HMG2 has DNA bending activity (6), our data suggest
      that HMG proteins may augment DNA fragmentation during apoptosis through changes
      in chromosome structure.

PMID- 9784392
TI  - Melatonin attenuates hydrogen peroxide toxicity in MCF7 cells only at
      pharmacological concentrations.
AB  - Melatonin is proposed to be oncostatic in mammary tissue, and one mechanism by
      which this hormone may elicit its possible oncostatic effect is as an oxygen
      radical scavenger. Therefore, we examined melatonin's abilities to act as an
      oxygen radical scavenger at physiological or pharmacological concentrations.
      Hydrogen peroxide at 400 microM killed 97% of treated MCF7 cells within 8 h, and
      following melatonin at 10(-5) and 10(-4) M concentrations only 76 and 64% of
      cells, respectively, were killed by hydrogen peroxide. However, melatonin at
      lower concentrations (10(-7) M) did not protect MCF7 cells. Moreover,
      pretreatment with melatonin (10(-5) or 10(-7) M) prior to hydrogen peroxide
      stress offered no further efficacy, and pretreatment with melatonin followed by
      the withdrawal of melatonin eliminated its protective effect from hydrogen
      peroxide toxicity. These findings indicate that melatonin acts directly as an
      antioxidant and does not stimulate antioxidant defenses in MCF7 cells that
      protect against hydrogen peroxide. Glutathione levels were examined to
      substantiate this hypothesis and were not altered by melatonin treatment. In
      conclusion, melatonin is an excellent oxygen radical scavenger at pharmacological
      concentrations, but not at physiological concentrations. Thus, loss of melatonin
      is unlikely to be important in oxidative scavenger mechanisms in human mammary
      cells.

PMID- 9784393
TI  - Activation of Proalpha2(I) collagen promoter during hepatic fibrogenesis in
      transgenic mice.
AB  - We previously identified the promoter sequence that is essential for basal and
      TGF-beta-stimulated transcription of alpha2(I) collagen gene (COL1A2). In the
      present study, we examined whether the promoter is activated during hepatic
      fibrogenesis by utilizing transgenic mice harboring the COL1A2 upstream sequence.
      Intraperitoneal CCl4 administration activated the -17 kb COL1A2 promoter more
      than 10-fold, whereas partial hepatectomy resulted in no significant change in
      the promoter activity. The non-parenchymal cell fraction, but not parenchymal
      hepatocytes, isolated from mice harboring the -313 COL1A2 promoter linked to a
      beta-galactosidase reporter gene contained large amounts of beta-galactosidase
      and endogenous COL1A2 mRNAs. beta-galactosidase activity in the cells from CCl4
      treated mice was significantly higher than in those from untreated animals. These
      results indicated that different molecular mechanisms control COL1A2
      transcription in CCl4-induced liver injury/fibrosis and physiological
      regeneration after partial hepatectomy, and that the -313 COL1A2 promoter is
      activated in a cell type-specific manner during hepatic fibrogenesis.

PMID- 9784394
TI  - Isolation and structure of pompilidotoxins, novel peptide neurotoxins in solitary
      wasp venoms.
AB  - Novel peptide neurotoxins, alpha- and beta-pompilidotoxins (alpha- and beta
      PMTXs), were purified from the venoms of the solitary wasps Anoplius samariensis
      and Batozonellus maculifrons. Their structures were analyzed mostly by MALDI-TOF
      MS, which were corroborated by solid-phase synthesis. alpha-PMTX, with 13 amino
      acid residues and the sequence of Arg-Ile-Lys-Ile-Gly-Leu-Phe-Gln-Asp-Leu-Ser-Lys
      Leu-NH2, greatly potentiates synaptic transmission of lobster leg muscle by the
      presynaptic mechanisms. beta-PMTX, in which the lysine residue at 12 position of
      alpha-PMTX was replaced with arginine, was more potent than alpha-PMTX.

PMID- 9784395
TI  - A protein tyrosine kinase of chloroplast thylakoid membranes phosphorylates light
      harvesting complex II proteins.
AB  - Phosphorylation of chloroplast thylakoid proteins, in particular light harvesting
      complex II (LHC II), is believed to play an important role in regulating
      photosynthetic electron transfer. Evidence supporting the involvement of multiple
      protein kinases in this system is mounting. We have re-examined pea thylakoid
      membranes and found evidence for a membrane-associated protein tyrosine kinase
      (PTK). Phosphorylation of many thylakoid proteins, including LHC II, is sensitive
      to treatment with the tyrosine kinase inhibitor genistein. Anti-phosphotyrosine
      antibodies react specifically with nine thylakoid proteins, two of which have
      been identified as components of LHC II. The phosphate associated with these two
      proteins is also resistant to strong base and acid treatment, further
      substantiating the assignment of phosphotyrosine. Potential interactions between
      this novel chloroplast PTK activity and the well-documented threonine kinase
      activities are discussed and the presence of a cascade of thylakoid protein
      kinases is proposed.

PMID- 9784396
TI  - The hCSE1/CAS protein is phosphorylated by HeLa extracts and MEK-1: MEK-1
      phosphorylation may modulate the intracellular localization of CAS.
AB  - hCSE1/CAS (CAS), the human homologue of the yeast chromosome segregation gene
      CSE1, is a nuclear transport factor that plays a role in proliferation and
      apoptosis. A MEK-1 phosphorylation sequence in CAS raises the possibility that
      MEK-phosphorylation regulates the function of CAS. CAS protein from cell extracts
      shows covalent charge modifications; one of these charge variants contains
      phosphotyrosine. CAS protein can be captured from cell extracts by immobilized
      anti-phosphotyrosine antibodies. We have produced recombinant protein fragments
      containing the N-terminal or central portion of CAS and found that the N-terminal
      fragment, which contains a putative MEK phosphorylation site, is phosphorylated
      by the HeLa extracts and MEK-1. Treatment of cells with an inhibitor of MEK-1
      phosphorylation in vivo changes the intracellular localization of CAS from
      predominantly cytoplasmic to nuclear. This suggests that a function of CAS in
      nuclear transport may be regulated by phosphorylation.

PMID- 9784397
TI  - Induction of a germination specific, low molecular weight, acid phosphatase
      isozyme with specific phosphotyrosine phosphatase activity in lentil (Lens
      esculenta) seeds.
AB  - A germination specific isozyme of acid phosphatase (EC 3.1.3.2) hydrolysing O
      phospho-L-Tyrosine, pH optima 5.5 is induced in lentil seeds. When seeds at 0 h,
      24 h and 36 h of germination are electrophorezed, native PAGE on specific enzyme
      staining shows several constitutive isozymes of acid phosphatases. At 48 h, an
      isozyme is induced which gradually decreases and then disappears at 108 h of
      germination. The short lived, induced isozyme is present in the embryo and seed
      coat but not in the plumule and the radical. Induction of this isozyme is
      inhibited by cycloheximide and actinomycin-D and increased by plant growth
      regulators such as heteroauxin and gibbrellic acid treatment during germination.
      The induced isozyme is a single 30 kD polypeptide, with subunit molecular mass of
      25 kD, shows activity for O-phospho-L-Tyrosine. It is strongly inhibited by
      vanadate (microM), molybdate, tungustate as also by iodoacetate, p
      chloromercuribenzoate and diethylpyrocarbonate. This study shows for the first
      time that the germination induced low molecular weight Acid phosphatase is a
      Tyrosine phosphatase super family class IV enzyme, having a role in cellular
      differentiation and development during seed germination.

PMID- 9784398
TI  - Gustin from human parotid saliva is carbonic anhydrase VI.
AB  - Gustin, a zinc-metalloprotein constituting about 3% of human parotid saliva
      protein was previously isolated and characterized as a single polypeptide chain
      of 37kDa with one mole of zinc tightly bound to the protein. It exhibited
      biological activity activating calmodulin dependent bovine brain cAMP
      phosphodiesterase and was decreased in saliva of patients with loss of taste in
      whom taste buds showed a specific pathological morphology. Determination of its
      primary structure by amino acid sequence revealed it was identical with carbonic
      anhydrase (CA) [EC 4.2.1.1] VI and had two N-linked glycosylation sites. Analysis
      by reverse phase HPLC and SDS-PAGE before and after deglycosylation confirmed a
      single peak with molecular weight of the purified protein being 37kDa, the
      deglycosylated protein, 33kDa. N-linked carbohydrate chains contained N-acetyl
      glucosamine, galactose, mannose, and fucose interior to di, tri and tetra
      sialyated termini. By isoelectric focusing five increasingly acidic pI values
      were determined consistent with addition of sialic acid as the terminal
      carbohydrate residue on the N-linked glycoforms of the protein. Gustin was found
      to exhibit CA activity but was inhibited by known CA inhibitors in a different
      manner than CA I or II. These findings, consistent with analysis of previous
      investigators, indicate that parotid saliva gustin is CA VI.

PMID- 9784399
TI  - Quantitative measurements for type 1 deiodinase messenger ribonucleic acid in
      human peripheral blood mononuclear cells: mechanism of the preferential increase
      of T3 in hyperthyroid Graves' disease.
AB  - To evaluate the regulatory mechanism of human Type 1 iodothyronine deiodinase
      (D1) gene expression, we measured the D1 mRNA levels in peripheral blood
      mononuclear cells (PBMC) in normal control subjects and in patients with Graves'
      disease. We used competitive reverse transcriptase-polymerase chain reaction with
      the deleted complimentary RNA of D1 as the standard for quantification. The D1
      mRNA levels in PBMC were increased significantly in patients with Graves' disease
      compared with that in normal controls. There was a significant (p < 0.01)
      positive correlation (r=0.698) between D1 mRNA level and serum T3 concentration.
      When PBMC from the normal volunteers were cultured with various doses of T3, the
      quantity of D1 mRNA increased significantly in a dose-dependent manner. These
      findings indicate that PBMC D1 mRNA is actually up-regulated by T3 in vivo, and
      we postulate that a vicious spiral of increasing T3 and D1 is responsible for the
      exacerbation of thyrotoxicosis in hyperthyroid Graves' disease.

PMID- 9784400
TI  - Identification of a novel stress activated kinase in kidney and heart.
AB  - We have previously described the patterns of stress kinase activation in rat
      kidney and heart in response to ischemia/reperfusion (Yin et al., 1997, J. Biol.
      Chem. 272, 19943-19950). During the course of these studies, we observed the
      activation of a novel kinase capable of phosphorylating c-Jun on serines 63 and
      73. The molecular weight of this kinase is approximately 37 kD, significantly
      below the molecular weight of all previously identified Jun N-terminal kinase
      (JNK) isoforms. The pattern of activation of this 37 kD kinase in response to
      ischemia/reperfusion in both kidney and heart is distinct from that of known JNK
      isoforms. Western analysis of human renal proximal tubular epithelial (RPTE)
      cells, using a non-isoform specific phospho-JNK antibody, revealed the
      phosphorylation (activation) of a 37 kD protein in response to hypoxia. The 37 kD
      protein in RPTE cells is phosphorylated by other stress stimuli capable of
      activating JNK. Western analysis of tissues, using a non-isoform specific JNK
      antibody, identifies a cross-reactive 37 kD protein expressed in the liver,
      thymus and lymph node which is likely to correspond to the 37 kDa stress
      activated kinase. The results of this study have led to the identification of a
      potentially novel kinase closely related to JNK but showing a distinct pattern of
      activation.

PMID- 9784402
TI  - Characterization of selachian egg case collagen.
AB  - The egg case of the dogfish Scyliorhinus canicula is a remarkable collagenous
      structure that combines mechanical strength and toughness with high permeability
      to small molecules and ions. The collagenous lamellae that form over 80% of the
      thickness of the case wall are secreted by the D-zone of the nidamental (oviducal
      gland). An acid-soluble collagen extracted from this zone and partially purified
      ran as a single band on a native gel at pH 4.3. A single band of identical
      mobility was extracted from egg cases removed from the oviducal gland. SDS-PAGE
      of both extracts revealed a major component with an apparent molecular weight of
      35 kDa and a minor component at 34 kDa. Neither of these components appeared to
      be glycosylated. Amino acid analysis of the partially purified collagen extracted
      from the oviducal gland revealed a composition similar to that of the collagenous
      lamellae of the egg case with glycine accounting for 16% and imino acids for 10%
      of the total residues. Partial N-terminal and internal sequences were obtained by
      Edman degradation for peptides extracted from the D-zone of the nidamental gland.
      Four of the internal sequence fragments showed repeated G-X-Y triplets showing
      them to be collagenous. These four fragments were novel but showed similarity to
      the triple-helical domains of mammalian type IV, X, and VI collagens. The
      noncollagenous N-terminal and pepsin-resistant sequences were unique, showing no
      significant similarity to known proteins in the database. Several possible N
      myristoylation and phosphorylation sites were identified in the noncollagenous
      sequences.

PMID- 9784401
TI  - Human lymphocyte heme oxygenase 1 as a response biomarker to inorganic arsenic.
AB  - We propose the use of human lymphocyte heme oxygenase 1 (HO1) as a biomarker of
      response to environmental arsenic exposure. We report the induction of HO1 in
      human lymphoblastoid cells (LBs) by arsenite in a dose-related manner. HO1 was
      identified by SDS-PAGE from its molecular weight and from its detection by
      Western blotting with anti-HO1. HO1 levels in LBs treated with arsenite increased
      by de novo synthesis as demonstrated by incorporation of 35S-methionine and by
      inhibition of HO1 synthesis by actinomycin D. The amount of HO1 in LBs was
      estimated by quantifying Western blots. HO1 was also induced by 10 microM cadmium
      or mercuric chloride. We suggest that circulating lymphocyte HO1 levels may be
      useful in assessing the biological activity of arsenic exposure in vivo under
      properly controlled conditions of simultaneous urinalysis for arsenic, cadmium,
      and mercury.

PMID- 9784403
TI  - cDNA sequence and deduced amino acid sequence of a fungal stress protein induced
      in Rhizopus nigricans by steroids.
AB  - cDNA clone was isolated from lambdagt11 library prepared from Rhizopus nigricans
      after growing the fungus in the presence of progesterone. Northern blot analysis
      of total RNA showed that expression of corresponding mRNA was up-regulated in R.
      nigricans after treatment with different steroids and after exposure of the
      fungus to heat shock or osmotic stress. Sequence analysis revealed an open
      reading frame for a 364-amino-acid polypeptide. The predicted amino acid sequence
      exhibited significant similarity to several sugar epimerases in two domains
      common to these enzymes. Our results suggest that the analyzed cDNA is coding for
      a fungal stress inducible protein belonging to sugar epimerases.

PMID- 9784404
TI  - Mechanical strain rapidly redistributes tyrosine phosphorylated proteins in human
      intestinal Caco-2 cells.
AB  - Repetitive strain stimulates proliferation and modulates differentiation in human
      Caco-2 intestinal epithelial cells via tyrosine kinase activity. We therefore
      sought to characterize strain modulation of tyrosine phosphorylation in Caco-2
      cells. Immunoblotting for phosphotyrosine demonstrated that repetitive strain (10
      cpm, 10% strain) rapidly increased tyrosine phosphorylation of 125-, 70-, 60-,
      and 50-kDa bands in the soluble fraction by 94+/-31, 145+/-21, 365+/-46, and
      1240+/-240%, respectively (p<0.05, n=4). However, strain decreased tyrosine
      phosphorylated band intensity of the 125-, 70-, 60-, and 50-kDa proteins in the
      particulate fraction by 81+/-17, 70+/-23, 79+/-7, and 59+/-23%, respectively
      (p<0.05, n=4). The decreased band intensity in the particulate fraction was not
      due to decreased tyrosine kinase activity because strain equally increased
      tyrosine kinase activity in both soluble and particulate fractions. Cyclic strain
      at a physiologically relevant amplitude and frequency appears to modulate the
      subcellular distribution of tyrosine phosphorylated proteins in human Caco-2
      intestinal cells.

PMID- 9784405
TI  - Expression of a gene trap reporter construct in a subset of cells in embryonic
      sites of hematopoiesis: evidence for alternative rRNA production in hematopoietic
      cells.
AB  - Three mouse lines were generated from independent gene trap events in embryonic
      stem cells. These lines express a betageo reporter gene in a subset of cells at
      sites of embryonic hematopoiesis. The 5' breakpoints of all three lines were
      found to lie in 45S ribosomal RNA transcription units. Expression was apparently
      linked to metabolic activity in these cells, since the kinetics of expression
      during embryogenesis matched that of cycling cells with colony forming unit
      spleen (CFU-S) potential. Expression was not seen in adult tissues unless the
      animals were treated with hydroxyurea, inducing synchronous entry of quiescent
      CFU-S into the cell cycle. Our results suggest that there is a subset of
      hematopoietic stem cells, which when actively proliferating, express the
      SAbetageo reporter construct from RNA polymerase I transcription units.

PMID- 9784406
TI  - Selection of DNA binding sites for human transcriptional regulator GATA-6.
AB  - The DNA-binding sites for transcriptional regulator GATA-6 were selected and
      amplified by means of a PCR-mediated random-site selection method involving
      filter binding and gel-mobility shift analysis using the zinc finger region of
      human GATA-6 fused with GST. Sequencing and comparison of the selected clones
      suggested that (A/T/C)GAT(A/T)(A) is the consensus binding sequence, which is
      similar to the GATA motif (A/T)GATA(A/G) and the gastric motif
      (G/C)PuPu(G/C)NGAT(A/T)PuPy. GATA-6 also binds to a similar sequence containing
      the GATC but not the GATG sequence. These results indicated that GATA-6 shows
      broader sequence specificity as to DNA binding. However, adenine is favored on
      both sides of the core for strong binding [AGAT(A/T)A], and the order of binding
      is GATA > GATT > GATC. Full-length human GATA-6 expressed in COS-1 cells showed
      essentially the same binding specificity, suggesting that the zinc finger region
      of GATA-6 mainly contributes to the selection of the binding sequence.
      Furthermore, the non-RI method presented in this paper is convenient for
      determination of the binding sites of other DNA-binding proteins.

PMID- 9784407
TI  - Cardiac expression of genes encoding putative adrenomedullin/calcitonin gene
      related peptide receptors.
AB  - Recent studies have suggested that adrenomedullin (AM) may play a role in the
      pathophysiology of heart disease, though the specific cardiac receptors involved
      have not been defined. RT-PCR cloned fragments of three putative AM/calcitonin
      gene-related peptide (CGRP) receptors were used to established a quantitative
      RNase protection assay to identify and quantitate expression of receptor mRNAs in
      heart and in cardiac myocytes. Intact rat heart expressed mRNA encoding the
      putative AM/CGRP receptors RDC1 and CRLR at 37- and 15-fold higher levels,
      respectively, than the AM-selective receptor L1, with a qualitatively similar
      profile in cultured neonatal cardiac myocytes. The high level of expression of
      RDC1 and CRLR suggests that both AM and CGRP may have direct actions on the
      cardiac myocyte via common receptors that can interact with either ligand.

PMID- 9784408
TI  - Cross-linking of intercellular adhesion molecule-1 induces interleukin-8 and
      RANTES production through the activation of MAP kinases in human vascular
      endothelial cells.
AB  - We investigated whether intercellular adhesion molecule-1 (ICAM-1) transduces
      outside-in signals for the production of chemokines IL-8 and RANTES in
      endothelial cells. Cross-linking of ICAM-1 induced IL-8 and RANTES mRNA
      expressions and increased their protein synthesis and secretions in endothelial
      cells. Furthermore, ICAM-1 cross-linking activated 44- and 42-kDa mitogen
      activated protein (MAP) kinases (ERK1 and ERK2) in endothelial cells, as
      indicated by the electrophoretic mobility shift of MAP kinases on SDS
      polyacrylamide gels. Finally, the specific MEK inhibitor PD98059 inhibited ICAM-1
      induced IL-8 and RANTES production in endothelial cells. Taken together, these
      results indicate that stimulation of ICAM-1 induces IL-8 and RANTES production
      through the activation of 44- and 42-kDa MAP kinases in endothelial cells,
      suggesting that ICAM-1-induced chemokine production in endothelial cells would
      further attract and activate leukocytes to induce intense inflammation.

PMID- 9784409
TI  - Intracellular expression of the anti-erbB-2 sFv N29 fails to accomplish efficient
      target modulation.
AB  - The use of intracellular single chain antibodies has recently emerged as a highly
      efficient method of down-regulating or ablating protein expression. In this
      regard, we have demonstrated that a single chain antibody directed against the
      extracellular domain of the erbB-2 molecule causes a specific toxicity in erbB-2
      positive tumor types. To further investigate the mechanism of this effect, we
      developed a second anti-erbB-2 sFv predicted to recognize an alternate
      extracellular epitope of the erbB-2 molecule. When produced as a secreted protein
      from the erbB-2 negative COS-1 cell line, this sFv binds specifically to erbB-2
      positive cells, indicating that cellular machinery is able to produce a properly
      folded and functional sFv protein. However, by several assays, this sFv was shown
      to be unable to retain the erbB-2 protein within the ER. These negative results
      have implications for the evaluation and utilization of sFv knockout strategies
      in experimental contexts.

PMID- 9784410
TI  - Identification of two novel 5' noncoding exons in human MNB/DYRK gene and
      alternatively spliced transcripts.
AB  - Previously, the comparison of human MNB/DYRK cDNA sequences with publicly
      available genomic DNA sequence made a conclusion that MNB/DYRK gene consists of
      11 exons spanning 100 kb. Here we found a novel human MNB/DYRK cDNA clone that
      has the 5' end different from any of those reported MNB/DYRK cDNAs. The 5' end of
      this cDNA resides in a CpG island associated with the NotI linking clone LL390
      that is located more than 50 kb upstream of the exon that contains an initiation
      codon ATG. Northern blot analysis indicated that almost all the MNB/DYRK
      transcripts start from the newly identified 5'-noncoding exon. PCR amplification
      of cDNAs from various human tissues indicated that some mRNAs contain an
      additional noncoding exon of 76 bp next to the 5'-end exon and there are at least
      three types of MNB/DYRK mRNAs containing alternatively spliced 5' exons including
      two novel exons. We now conclude that human MNB/DYRK gene consists of 13 exons
      (not 11 exons) spanning about 150 kb (not 100 kb).

PMID- 9784411
TI  - Novel configurations of the hammerhead ribozyme: increased activity and reduced
      magnesium ion requirement.
AB  - The hammerhead ribozyme is one of the smallest of known catalytic RNAs. Its
      structure and mechanism have been examined using a broad range of approaches.
      Recently, crystal structures of the hammerhead have been reported. Within the
      crystal the hammerhead exists in a Y-shaped configuration in which helices I and
      II form the adjacent upper arms, while helix III forms the lower leg of the Y.
      Based on these findings, hammerheads in which helix I and II are constrained to
      remain adjacent and roughly parallel are expected to be catalytically active. We
      have examined this possibility with two novel hammerhead configurations, circular
      and circular/hairpin. These circular and circular/hairpin hammerhead ribozymes
      possess activity comparable to, and in some cases even greater than, non
      constrained hammerheads. Since these novel ribozymes are constrained into a
      closed, and active conformation, they offer advantages for structure/function
      studies. Additionally, these novel ribozymes will be adventitious for antisense
      mediated gene inhibition, since they possess increased activity and a reduced
      requirement for magnesium ion, and are expected to be more resistant to nuclease
      degradation.

PMID- 9784412
TI  - In vitro binding and signaling profile of the novel mu opioid receptor agonist
      endomorphin 2 in rat brain membranes.
AB  - The recently discovered endogenous mu receptor selective endomorphin 2 was
      prepared in tritiated form by a catalytic dehalogenation method resulting in a
      specific radioactivity of 1.98 TBq/mmol (53.4 Ci/mmol), and used for in vitro
      labelling of rat brain membranes. The binding was saturable, stereospecific and
      of high affinity (Kd: 0.97 and 1.12 nM based on kinetic and equilibrium binding
      studies, respectively). The maximal number of binding sites (Bmax) was found to
      be 114.8 fmol/mg protein. [3H]Endomorphin 2 was displaced by mu-receptor
      selective specific peptides and heterocyclic compounds with high affinity,
      whereas kappa and delta receptor specific ligands were much less potent. The Ki
      values of endomorphin 1 and 2 in inhibiting [3H]naloxone binding increased by 15
      fold in the presence of 100 mM NaCl which indicates the agonist property of these
      peptides. Endomorphins stimulated [35S]GTPgammaS binding and inhibited adenylyl
      cyclase activity which also provides evidence for the agonist character of
      endomorphins.

PMID- 9784413
TI  - Natural methylamine osmolytes, trimethylamine N-oxide and betaine, increase tau
      induced polymerization of microtubules.
AB  - The natural osmolyte trimethylamine N-oxide (TMAO) at 200 mM increases the extent
      and the rate of formation of polymerized microtubule (MT) complex caused by tau.
      TMAO at this concentration has no effect on tubulin alone. Urea at 200 mM blocks
      tubulin assembly caused by tau, but this inhibition can be reversed by an equal
      amount of TMAO. Besides TMAO, betaine, another natural osmolyte, was found to
      have the same effects on MT as TMAO. On the contrary, glycerol (a carbohydrate
      osmolyte) and glycine (an amino acid osmolyte) do not increase tau-induced MT
      assembly. The mechanism by which TMAO and betaine enhance tau's effectiveness is
      not known, but physical studies suggest that the secondary structure of tau is
      not appreciably changed by 200 mM TMAO. This is the first report showing that
      natural osmolytes, TMAO and betaine, at a near physiological concentration are
      able to stimulate tau-induced tubulin assembly.

PMID- 9784415
TI  - The role of alpha2 beta1 and alpha3 beta1 integrin receptors in the initial
      anchoring of MDA-MB-231 human breast cancer cells to cortical bone matrix.
AB  - Molecular mechanisms involved in the rapid attachment of the human breast cancer
      cell line MDA-MD-231 to cortical bone matrix were studied. The attachment of MDA
      MD-231 cells to cortical bone disks could be blocked by 75% when cells were
      pretreated with a monoclonal antibody to the beta1-subunit of the integrin
      family. Monoclonal antibodies against the alpha2, alpha3, and alpha5 integrin
      subunits inhibited the attachment by 76, 26, and 8 % respectively. Collagenase
      type I and collagen type I antibody blocked the cell attachment by 45 and 50 %
      whereas pretreatment of the cells with soluble collagen type I blocked the
      attachment by 85 %. Our study with a panel of cancer cell lines further showed a
      close correlation between alpha2 beta1 and alpha3 beta1 integrin receptor
      expression and the capability to attach to cortical bone. These receptors appear
      to be the key receptors utilized by cancer cells for the initial attachment to
      cortical bone, and this could facilitate the localization of alpha2 beta1 and
      alpha3 beta1 expressing cancer cells to the skeleton.

PMID- 9784414
TI  - Involvement of polyamines in retinoblastoma protein phosphorylation.
AB  - Hepatocyte growth factor (HGF) increased both levels of phosphorylated and non
      phosphorylated forms of retinoblastoma protein (RB) in primary cultured rat
      hepatocytes. Combined treatment of HGF and a specific inhibitor of ornithine
      decarboxylase (ODC), alpha-difluoromethylornithine (DFMO), reduced the levels of
      hyper-phosphorylated and hypo-phosphorylated forms of RB and increased the levels
      of the non-phosphorylated form, compared to HGF alone, but did not affect the
      total level of RB. Polyamines added exogenously overcame the effects of DFMO;
      they increased hyper- and hypo-phosphorylated forms and decreased non
      phosphorylated RB. TGF-beta1 inhibited the increases in ODC activity, RB
      phosphorylation, and DNA synthesis induced by HGF. However, polyamines added
      exogenously could not overcome the inhibition by RB phosphorylation and DNA
      synthesis by TGF-beta1. These results suggest that polyamines are involved in the
      phosphorylation of RB, but the inhibition of polyamine biosynthesis by TGF-beta1
      did not result in the inhibition of RB phosphorylation and DNA synthesis.

PMID- 9784417
TI  - cDNA excision in stable retroviral cDNA transfectants is prevented by R removal.
AB  - The present study provides evidence on the occurrence of DNA rearrangement
      between the redundant 5' and 3' R domains of equine infectious anemia virus
      (EIAV) Tat cDNA. This was correlated with a gradual loss of cDNA copy number
      concomitantly with a decrease in gene expression. Removal of the 5' RU5 abolished
      rearrangement and stabilized Tat expression in EIAV tat cDNA transfectants. Our
      data suggest that prior removal of the 5' R from cloned retroviral cDNAs can
      impede DNA rearrangement, thus preventing cDNA excision that frequently occurs
      and hinders permanent expression of retroviral cDNAs in stable transfectants.

PMID- 9784416
TI  - Suppression of transformed phenotypes of Ha-ras-transformed NIH3T3 cells by
      caspase-2.
AB  - Biological effects of caspases-1, -2 and -3 have been investigated by
      transfection of these human cDNAs into activated c-Ha-ras-transformed NIH3T3
      mouse fibroblasts. High expression of caspase-2 but not caspase-1 or -3 induced
      flat revertant cells which lost the ability of anchorage-independent growth.
      Notably, these revertants contained a reduced amount of Ras protein. These
      suggest that caspase-2 exhibited a tumor-suppressive activity by affecting the
      expression level of Ras protein.

PMID- 9784418
TI  - Molecular cloning and characterization of human PDE8B, a novel thyroid-specific
      isozyme of 3',5'-cyclic nucleotide phosphodiesterase.
AB  - We have identified a novel human isozyme of 3',5'-cyclic nucleotide
      phosphodiesterase (PDE), which we designated PDE8B. cDNA of 2844 bp encoding the
      C-terminal 659 amino acids of PDE8B was cloned following the identification of an
      expressed sequence tag (EST) obtained through a search of the EST database. The
      predicted protein sequences of PDE8B showed highest homology (65% identity, 83%
      similarity) to that of PDE8A. Northern blot analysis indicated that the mRNA
      encoding PDE8B is expressed specifically and abundantly in thyroid gland as a
      approximately 4.2 kb mRNA, in contrast to the wide expression of PDE8A mRNA in
      various tissues. The carboxyl-terminal 584 amino acids of PDE8B were expressed in
      E.coli as a fusion protein. The recombinant PDE8B exhibited cAMP PDE activity
      which was not inhibited by various PDE inhibitors including vinpocetine,
      milrinone, rolipram, and IBMX with the exception of dipyridamole which caused 50%
      inhibition at a concentration of 40 microM. cAMP hydrolytic activity was
      unaffected by cGMP and no cGMP PDE hydrolysis were detectable at concentrations
      up to 100 microM. These findings suggest that PDE8B is a new member of the PDE8
      family.

PMID- 9784419
TI  - MUC4 is a major component of salivary mucin MG1 secreted by the human
      submandibular gland.
AB  - High molecular weight salivary mucin (MG1) is an important component of saliva,
      contributing to the lubricative and tissue-protective functions of this
      biological fluid. We have shown previously that the human mucin gene MUC5B is
      expressed at high levels in sublingual gland and is a significant constituent of
      MG1. Since many epithelia express multiple mucin genes, it seemed likely that MG1
      in salivary secretions is also a heterogeneous mixture of mucin gene products.
      The aim of this study was to determine whether MUC4, a mucin shown in Northern
      blotting experiments to be expressed in salivary glands, was a significant
      protein component of MG1 in salivary secretions. Two cDNA clones containing MUC4
      tandem repeats were isolated from a human submandibular gland cDNA library. In
      addition, recombinant MUC4 produced in a bacterial expression system cross
      reacted with an antibody directed against deglycosylated MG1. This shows
      conclusively that human salivary mucin MG1 contains both MUC5B and MUC4 gene
      products suggesting that each mucin may perform distinct functions in the oral
      cavity.

PMID- 9784420
TI  - Growth and differentiation of rat hepatocytes: changes in transcription factors
      HNF-3, HNF-4, STAT-3, and STAT-5.
AB  - The liver enriched transcription factors HNF-3 and HNF-4 are known to play major
      roles in development and differentiation of hepatocytes. STAT-3 and STAT-5 are
      signaling peptides activated by a variety of cytokines and growth factors
      including HGF and EGF. Their role in hepatocyte growth and differentiation is yet
      to be determined. We examined protein expression and DNA binding activities of
      these transcription factors in a hepatocyte culture system in which the
      hepatocytes first de-differentiate and proliferate. Overlaying proliferating
      hepatocytes with EHS-matrix led to an increase in HNF-4 protein and DNA-binding
      activity. STAT-5 DNA binding activity was only slightly effected by EHS-matrix.
      HNF-3 and STAT-3 DNA-binding activities were reduced in the presence of EHS
      matrix. This is consistent with the role of HNF-3 as the major initiating
      transcription factor involved in embryonic liver development and suggests, that
      STAT-3 might also play a role in growth and differentiation of hepatocytes.

PMID- 9784421
TI  - Activated rat stellate cells express c-met and respond to hepatocyte growth
      factor to enhance transforming growth factor beta1 expression and DNA synthesis.
AB  - Hepatocyte growth factor (HGF) decreases transforming growth factor beta1
      (TGFbeta1) levels in the liver and attenuates hepatic fibrosis caused by
      dimethylnitrosamine in rats. In the liver, HGF is presumed to act predominantly
      on parenchymal cells, and TGFbeta1 is produced mainly by mesenchymal cells. In
      hepatic fibrosis, stellate cells play a central role with undergoing activation,
      which also occurs when the cells are cultured on plastic. Thus, we wondered if
      HGF could act directly on stellate cells. c-Met was detected in rat stellate
      cells activated by culture for 10 days, but not in the cells cultured for 3 days.
      Specific binding of HGF to the activated cells was determined, and Scatchard
      analysis indicated an apparent Kd of 1.5 nM. c-Met mRNA was detected in freshly
      isolated stellate cells from rats treated with carbon tetrachloride for 8 weeks,
      but not in those cells from normal rats. These results indicate that stellate
      cells express c-met when activated in vitro and in vivo. HGF enhanced TGFbeta1
      production and DNA synthesis in the activated cells.

PMID- 9784423
TI  - The C-terminal segment is essential for maintaining the quaternary structure and
      enzyme activity of the nitric oxide forming nitrite reductase from Achromobacter
      cycloclastes.
AB  - We have constructed and expressed a series of mutated nitrite reductase (NIR)
      mutants based on the sequence of NIR from Achromobacter cycloclastes. Deleting a
      pentapeptide, an undecapeptide, or a heptadecapeptide from the C-terminus of NIR
      resulted in a series of C-terminal deletion mutated proteins designated as NIR-5,
      NIR-11, and NIR-17, respectively. A C-terminally extended mutated protein, NIR+8,
      was also produced, which contains an extra octapeptide attached to the C-terminus
      of the wild-type NIR. An SDS-PAGE system using tris-tricine buffer could retain
      the native NIR in its trimeric form, thus offering a convenient method to check
      the quaternary structure of NIR analogs. By using this system it was found that
      NIR-5 was maintained as trimer and retained 72% of wild-type enzyme activity.
      However, both NIR-11 and NIR-17 behaved as monomers in the SDS-PAGE and lost all
      their enzyme activity. Although NIR+8 maintained its trimeric structure it was
      enzymatically inactive. These results clearly indicate that the C-terminal
      undecapeptide is essential for maintaining the quaternary structure as well as
      the full enzymatic activity, as expected from the X-ray crystallography studies.

PMID- 9784422
TI  - Osteoprotegerin production by human osteoblast lineage cells is stimulated by
      vitamin D, bone morphogenetic protein-2, and cytokines.
AB  - Osteoprotegerin (OPG), a newly discovered member of the tumor necrosis factor
      receptor family, is a potent inhibitor of osteoclastogenesis. The overexpression
      of OPG in transgenic mice leads to osteopetrosis, whereas targeted ablation of
      OPG in knock-out mice leads to severe osteoporosis. However, the production and
      regulation of OPG in normal human bone has not been studied. Thus, we assessed
      OPG mRNA expression and protein secretion in human osteoblastic lineage cells.
      1,25-Dihydroxyvitamin D3 (10(-7) M) increased OPG mRNA levels by 90 and 50% in a
      fetal osteoblastic cell line (hFOB) and normal trabecular osteoblastic cells
      (hOB) cells, respectively, but did not affect OPG mRNA levels in a marrow stromal
      preosteoblastic (hMS) cell line. Interleukin (IL)-1beta (5 x 10(-9) M), tumor
      necrosis factor (TNF)-alpha (9 x 10(-9) M), and bone morphogenetic protein (BMP)
      2 (100 ng/ml) also increased OPG mRNA levels in hFOB cells by 4-, 6-, and 4-fold,
      respectively. Treatment with 1,25-dihydroxyvitamin D3, IL-1beta, TNF-alpha, and
      BMP-2 increased OPG protein production by hFOB cells by 60, 390, 300, and 80%,
      respectively (P < 0.001). Because it is expressed in various types of human
      osteoblastic cells, and is stimulated by vitamin D, BMP-2 and cytokines, OPG may
      be an important paracrine modulator of bone remodeling.

PMID- 9784424
TI  - Calcium buffering capacity of neuronal cell cytosol measured by flash photolysis
      of calcium buffer NP-EGTA.
AB  - N1E-115 mouse neuroblastoma cells were injected with a calcium buffer/indicator
      solution to allow both ratiometric measurement of free calcium concentration and
      the release of calcium ions upon UV flash. The solution contained sulforhodamine,
      a marker dye used to estimate the volume injected; fluo-3, a calcium indicator,
      and NP-EGTA, a high affinity calcium-selective buffer that is converted by UV
      flash to products with negligible calcium affinity. The calcium increase recorded
      upon UV irradiation (Delta[Ca2+]i) was small for small injection volumes,
      increased with larger injection volumes, but approached a plateau at the largest
      injection volumes. From this relation we estimate the buffering capacity of the
      cytosol as 1700 ions bound per ion free.

PMID- 9784425
TI  - The p16(INK4A) protein and flavopiridol restore yeast cell growth inhibited by
      Cdk4.
AB  - Cyclin-dependent kinase 4 (Cdk4) activity is misregulated in most cancers. Loss
      of Cdk4 regulation can occur through overexpression of Cdk4 catalytic subunit or
      its regulatory partner cyclin D1, or if the Cdk4-specific inhibitory protein
      p16(INK4A) is inactive. We have attempted to express the two human subunits, Cdk4
      and cyclin D1, in the yeast Saccharomyces cerevisiae. Surprisingly, expression of
      Cdk4 alone, under control of the strong GAL promoter, inhibits cell growth.
      Coexpression of both subunits allows formation of an active Cdk4-cyclin D1
      complex which accentuates growth arrest. In cells expressing Cdk4 only, growth is
      restored by overexpressing human Cdc37, a Cdk4-binding molecular chaperone.
      Interestingly, the effect of Cdk4 on yeast is also overcome by both p16- and p21
      families of Cdk-inhibitory proteins. Moreover, flavopiridol, a compound which
      inhibits Cdk4 enzyme activity, restores cell division. The fact that p16(INK4A)
      and flavopiridol negate Cdk4-mediated suppression of yeast cell growth implies
      that this simple system can be used as a screen for identifying Cdk4-specific
      antagonists which may mimic p16(INK4A) in the cancer cell cycle.

PMID- 9784426
TI  - Bacterial lipopolysaccharide increases interleukin-6 and prostaglandin release in
      rat cortical type I astrocytes by different mechanisms: role of anti-inflammatory
      agents.
AB  - LPS stimulated IL-6 release in a concentration-dependent manner from rat cortical
      type I astrocytes. This stimulatory action was completely abolished by
      Dexamethasone (DEX), but was not affected by indomethacin (IND), a 5
      cyclooxigenase inhibitor. LPS-induced IL-6 release was partially inhibited by BW
      4AC, a 5-lipoxygenase inhibitor. LPS concentration-dependently increased the
      release of PGE2 from type I astrocytes, an effect completely inhibited by IND. To
      rule out the possibility that DEX was inhibiting LPS-induced IL-6 release by
      blocking IL-6 gene expression, we tested the effect of DEX on interleukin
      1beta(IL-1)-induced IL-6 release. DEX slightly inhibited IL-1-induced IL-6
      release, while IL-1 releasing action on IL-6 was significantly reduced by IND.
      The involvement of nitric oxide (NO) generation on LPS-induced IL-6 release was
      also studied. We found that L-NO-arginine, an inhibitor of nitric oxide synthase,
      concentration-dependently reduced LPS-induced IL-6 release in astrocytes. In
      conclusion, we provide evidence that LPS action on IL-6 and PGE2 release can be
      ascribed to the activation of different transduction mechanisms, which can be
      pharmacologically dissected with the aid of anti-inflammatory drugs.

PMID- 9784427
TI  - Activation of Fgf8 in S115 mouse mammary tumor cells is associated with genomic
      integration of mouse mammary tumor virus.
AB  - Fgf8 is an embryonally expressed mitogenic fibroblast growth factor which has
      transforming capacity. It is expressed in S115 mouse mammary tumor cells (S115
      cells) and in parental tumors of DD/Sio mice as well as in some human breast and
      prostate cancer cell lines. In S115 cells androgens induce the expression of Fgf8
      which seems to be associated with the androgen-maintained malignant phenotype of
      the cells. S115 cells also contain and express Mtv proviruses known to
      insertionally activate oncogenes in other tumor cells. Here we studied the
      possibility of insertional activation of Fgf8 in S115 cells by MMTV proviral
      integration. We demonstrate by Southern blotting that the genomic DNA from DD/Sio
      tumors and S115 cells contains Mtv-sequences (Mtv-6 and Mtv-17) which are not
      found in the DNA from spleen or liver of the DD/Sio mice. In addition, the newly
      integrated Mtv-6 was localized to the DNA fragment containing the Fgf8 gene.
      Furthermore, the expression of Fgf8 mRNA in DD/Sio tumors and S115 cells was not
      found in mammary gland or spleen and liver of DD/Sio mice. In S115 cells, Fgf8
      mRNA expression was induced in parallel to MMTV mRNA by androgen and
      glucocorticoids which supports the possibility that Fgf8 is controlled by the
      steroid-regulated MMTV-LTR. In conclusion, our data provide evidence that the
      insertion of MMTV into the DD/Sio tumor DNA is associated with the
      transcriptional activation of Fgf8 in DD/Sio tumor and consequently in S115 mouse
      mammary tumor cells.

PMID- 9784428
TI  - A qualitative and quantitative risk assessment of snuff dipping.
AB  - The presence of highly carcinogenic tobacco-specific nitrosamines (TSNA) in snuff
      has been a matter of serious concern. However, the levels of TSNA in such
      products may differ by orders of magnitude depending on origin and manner of
      processing, and the mere presence of such agents at low levels does hardly
      constitute a meaningful prerequisite for classifying all types of snuff as human
      carcinogens. Reviewing available epidemiological evidence, a wide discrepancy is
      found for estimated cancer risk associated with snuff dipping derived from on one
      hand previous investigations conducted in the United States and on the other from
      recent extensive Swedish epidemiological studies. In spite of the fact that
      approximately 20% of all grown-up Swedish males use moist snuff, it has not been
      possible to detect any significant increase in the incidence of cancer of the
      oral cavity or pharynx-the prevalence of which by international standards remains
      low in this country. Further, there is insufficient evidence for a causal link
      between the use of Swedish snuff and increased risk for cardiovascular disease.
      Dissimilarities in the content of TSNA in oral snuff products may represent one
      important reason for the different outcomes of the epidemiological surveys
      conducted in the United States and Sweden. Bioassays using pure TSNA in rodents
      appear to give exaggerated risk estimates for humans, a discrepancy that could be
      ascribed to species-related differences in the relation between exposure and DNA
      target dose and/or adduct repair rates, as well as to the presence of
      anticarcinogens in snuff. Although a small risk cannot be excluded, the use of
      smokeless tobacco products low in TSNA which now are available on the market
      entails a risk that at any rate is more than 10 times lower than that associated
      with active smoking. Nevertheless, due to the decisive role of potent TSNA in
      determining possible cancer risks in users of smokeless tobacco, and due to the
      fact that large variations in the concentrations may occur, adequate control
      measures should be taken to keep the levels of these nitrosamines in smokeless
      tobacco products as low as is technically feasible.

PMID- 9784429
TI  - Expanded clinical observations in toxicity studies: historical perspectives and
      contemporary issues.
AB  - Recent or proposed changes in major testing guidelines require expanded clinical
      observations (ECOs) for a wide variety of toxicity studies in animals. ECOs
      supplement the simple cageside and hand-held observations traditionally employed
      during such studies. The new guidelines specify out-of-cage observations [e.g.,
      posture, gait, and reactivity to various stimuli (e.g., auditory, tactile,
      noxious)] using defined scales and are intended as a Tier 1 screen for
      neurotoxicity. These new guidelines imply an elevation in the status of clinical
      observations to equivalency with other major categories of toxicity end points,
      such as anatomic and clinical pathology. The increased importance of neurological
      end points in routine studies indicates that there will be a need for many
      trained professionals to generate and interpret the results of ECOs. However,
      currently there is wide variation in the training and experience of individuals
      who conduct and interpret ECOs. The value of ECO data will be increased when
      industry standards for conducting and interpreting ECOs are systematized and
      elevated to the level of those for anatomic and clinical pathology.

PMID- 9784430
TI  - The prevalence of chromium allergy in the United States and its implications for
      setting soil cleanup: a cost-effectiveness case study.
AB  - Hexavalent chromium [Cr(VI)] elicits allergic contact dermatitis (ACD) among
      previously sensitized individuals, and some regulatory agencies have suggested
      the need for Cr(VI) soil standards that are protective of this health end point.
      To assess the cost effectiveness of implementing ACD-based standards, it is
      necessary to understand the prevalence of Cr(VI) sensitivity in the general
      population. More than 30 published studies from 1950 to 1997 were reviewed to
      determine the prevalence of Cr(VI) sensitivity. No random survey of the general
      United States (U.S.) population has been performed to date, but the prevalence of
      Cr(VI) sensitization among North American clinical cohorts (e.g., patients of
      dermatological clinics) was reported to be 1% in 1996. The prevalence of Cr(VI)
      sensitivity among the general U.S. population is estimated to be 0.08%. This
      estimate was calculated by dividing the current U.S. clinical prevalence estimate
      (1%) by the ratio of Cr(VI) sensitization in clinical vs general populations in
      The Netherlands (12). A retrospective cost/benefit analysis for sites in Jersey
      City, New Jersey, suggests that remediation of soils to protect against
      elicitation of ACD in sensitized individuals is not a cost-effective use of
      public health resources.

PMID- 9784431
TI  - Calculation of benchmark doses for reproductive and developmental toxicity
      observed after exposure to isopropanol.
AB  - Reproductive, including developmental, toxicity risk assessment has typically
      relied on estimation of toxicity criteria values derived from no-observed-adverse
      effect levels (NOAELs). The benchmark dose (BMD) approach has been proposed as an
      alternative that avoids problems with NOAELs. In this analysis of the
      reproductive and developmental toxicity observed in a multigeneration study of
      rats exposed to isopropanol, the BMD approach has been applied to all effects
      exhibiting significant dose-response relationships. The BMD estimates were very
      consistent across models and across end points; they were within the range of
      doses (100 to 500 mg/kg/day) that has been suggested as being the NOAEL. The use
      of the BMD approach for analysis of isopropanol reproductive toxicity is shown to
      avoid the experiment-specific argument of whether a particular treatment has
      induced statistically significant differences, compared to controls, in favor of
      the estimation of experiment-independent doses corresponding to risk levels of
      interest. The consistency of the BMD estimates, with values of about 420
      mg/kg/day, suggests that, for isopropanol, the available multigeneration study
      data may provide a suitable basis for considering safe exposure.

PMID- 9784433
TI  - Health effects classification and its role in the derivation of minimal risk
      levels: developmental effects.
AB  - Agency for Toxic Substances and Disease Registry (ATSDR) utilizes chemical
      specific minimal risk levels (MRLs) to assist in evaluating the public health
      risk associated with exposure to hazardous substances. The MRLs are derived based
      on the health effects data compiled from current literature searches and
      presented in ATSDR's toxicological profiles. Health effects are categorized
      according to their degree of severity (e.g., serious, less serious, minimal, and
      not adverse). This evaluation is important, because each respective category can
      be assigned a different amount of uncertainty, thus affecting the final value of
      the calculated MRL. From the total of 272 MRLs derived as of December 1997, 21
      were based on developmental effects. ATSDR's ranking of developmental health
      effects as described in the Guidance for Developing Toxicological Profiles and
      specific examples of how the categorized health effects were used in MRL
      derivations are provided in this paper.

PMID- 9784432
TI  - Potency equivalency factors for some polycyclic aromatic hydrocarbons and
      polycyclic aromatic hydrocarbon derivatives.
AB  - Potency equivalency factors (PEFs) for cancer induction relative to
      benzo[a]pyrene have been derived for 21 polycyclic aromatic hydrocarbons (PAHs)
      and PAH derivatives based on a data preference scheme. PEFs have been derived
      only for PAHs with demonstrated carcinogenicity in bioassays. Cancer potency
      values and inhalation unit risks are presented for four additional carcinogenic
      PAHs based on expedited risk assessments conducted for California's Proposition
      65. A much larger number of PAHs and PAH derivatives are considered mutagenic or
      genotoxic and may have limited evidence for carcinogenicity, but these compounds
      are not considered in this evaluation. New cancer bioassay data and possibly
      structure-activity analysis may indicate that additional PAHs are carcinogenic.
      Thus, additional PAHs may be identified as potential human carcinogens when such
      data become available. However, until that time the PEFs proposed for use in risk
      assessment were estimated only for PAHs currently classified as carcinogens.

PMID- 9784434
TI  - The use of hematological effects in the development of minimal risk levels.
AB  - The Agency for Toxic Substances and Disease Registry (ATSDR) derives minimal risk
      levels (MRLs) to assist in evaluating risk of adverse health effects in
      individuals exposed to hazardous substances. MRLs are derived from published
      values identifying no-observed-adverse-effect levels (NOAELs) or lowest-observed
      adverse-effect levels (LOAELs) in animal or human studies. The most sensitive end
      points are used. To date, 4 inhalation MRLs and 13 oral MRLs have been derived
      from hematological end points for 12 substances. This paper provides a brief
      overview of the hematological system, examples of hematological end points, and
      the MRL for substances with hematological end points.

PMID- 9784435
TI  - Report on cumulative dietary risk assessment of organophosphorus insecticides is
      flawed.

PMID- 9784436
TI  - Is the use of linear low-dose extrapolation still justified for carcinogens?

PMID- 9784437
TI  - Assessing heart disease risk in primary care. Cholesterol lowering should be just
      one part of a multiple risk factor intervention.

PMID- 9784438
TI  - Revalidation for doctors. Should reflect doctors' performance and continuing
      professional development.

PMID- 9784439
TI  - Breaks without bruises. Are common and can't be said to rule out non-accidental
      injury.

PMID- 9784440
TI  - House dust mite allergen avoidance in asthma. Benefits unproved but not yet
      excluded.

PMID- 9784441
TI  - Is medical school selection discriminatory? New data should be used as a catalyst
      for change.

PMID- 9784443
TI  - Hypersensitivity revisited 

PMID- 9784442
TI  - House dust mite control measures in the management of asthma: meta-analysis.
AB  - OBJECTIVE: To determine whether patients with asthma who are sensitive to mites
      benefit from measures designed to reduce their exposure to house dust mite
      antigen in the home. DESIGN: Meta-analysis of randomised trials that investigated
      the effects on asthma patients of chemical or physical measures to control mites,
      or both, in comparison with an untreated control group. All trials in any
      language were eligible for inclusion. SUBJECTS: Patients with bronchial asthma as
      diagnosed by a doctor and sensitisation to mites as determined by skin prick
      testing, bronchial provocation testing, or serum assays for specific IgE
      antibodies. MAIN OUTCOME MEASURES: Number of patients whose allergic symptoms
      improved, improvement in asthma symptoms, improvement in peak expiratory flow
      rate. Outcomes measured on different scales were combined using the standardised
      effect size method (the difference in effect was divided by the standard
      deviation of the measurements). RESULTS: 23 studies were included in the meta
      analysis; 6 studies used chemical methods to reduce exposure to mites, 13 used
      physical methods, and 4 used a combination. Altogether, 41/113 patients exposed
      to treatment interventions improved compared with 38/117 in the control groups
      (odds ratio 1.20, 95% confidence interval 0.66 to 2.18). The standardised mean
      difference for improvement in asthma symptoms was -0.06 (95% confidence interval 
      0.54 to 0.41). For peak flow rate measured in the morning the standardised mean
      difference was -0.03 (-0.25 to 0.19). As measured in the original units this
      difference between the treatment and the control group corresponds to -3 l/min
      (95% confidence interval -25 l/min to 19 l/min). The results were similar in the
      subgroups of trials that reported successful reduction in exposure to mites or
      had long follow up times. CONCLUSION: Current chemical and physical methods aimed
      at reducing exposure to allergens from house dust mites seem to be ineffective
      and cannot be recommended as prophylactic treatment for asthma patients sensitive
      to mites.

PMID- 9784445
TI  - The hippocratic oath 

PMID- 9784444
TI  - Perils of opera 

PMID- 9784446
TI  - Factors affecting likelihood of applicants being offered a place in medical
      schools in the United Kingdom in 1996 and 1997: retrospective study.
AB  - OBJECTIVE: To assess the relation between a range of measures and the likelihood
      of applicants to medical schools in the United Kingdom being offered a place
      overall and at each medical school, with particular emphasis on ethnic minority
      applicants. DESIGN: Data provided by the Universities and Colleges Admissions
      Service on 92 676 applications to medical schools from 18 943 candidates for
      admission in 1996 and 1997. Statistical analysis was by multiple logistic
      regression. MAIN OUTCOME MEASURES: Receipt of a conditional or unconditional
      offer of a place at medical school. RESULTS: Eighteen separate measures were
      independently associated with the overall likelihood of receiving an offer.
      Applicants from ethnic minority groups were disadvantaged, as were male
      applicants, applicants applying late in the selection season, applicants making
      non-medical (so called insurance) choices, applicants requesting deferred entry
      (so called gap year), and applicants at further or higher education or sixth form
      colleges. Analysis at individual medical schools showed different patterns of
      measures that predicted offers. Not all schools disadvantaged applicants from
      ethnic minority groups and the effect was stable across the two years, suggesting
      structural differences in the process of selection. The degree of disadvantage
      did not relate to the proportion of applicants from ethnic minority groups.
      CONCLUSIONS: The data released by the Council of Heads of Medical Schools allow a
      detailed analysis of the selection process at individual medical schools. The
      results suggest several areas in which some candidates are disadvantaged, in
      particular those from ethnic minority groups. Similar data in the future will
      allow monitoring of changes in selection processes.

PMID- 9784447
TI  - Importance of bruising associated with paediatric fractures: prospective
      observational study.

PMID- 9784448
TI  - Prevalence of congenital anterior abdominal wall defects in the United Kingdom:
      comparison of regional registers.

PMID- 9784449
TI  - Preventing ischaemic heart disease in one general practice: from one patient,
      through clinical audit, needs assessment, and commissioning into quality
      improvement.

PMID- 9784452
TI  - Time trend analysis and variations in prescribing lipid lowering drugs in general
      practice.

PMID- 9784451
TI  - From trial data to practical knowledge: qualitative study of how general
      practitioners have accessed and used evidence about statin drugs in their
      management of hypercholesterolaemia.
AB  - OBJECTIVES: To explore how general practitioners have accessed and evaluated
      evidence from trials on the use of statin lipid lowering drugs and incorporated
      this evidence into their practice. To draw out the practical implications of this
      study for strategies to integrate clinical evidence into general medical
      practice. DESIGN: Qualitative analysis of semistructured interviews. SETTING:
      General practices in Lothian. SUBJECTS: 24 general practitioners selected to
      obtain a heterogeneous sample. RESULTS: Respondents were generally aware of the
      evidence relating to the use of statins in secondary prevention of coronary heart
      disease, but they were less clear about the evidence in primary prevention. The
      benefits of statins in secondary prevention were clearer to them and the social
      and economic issues less complex than was the case for use in primary prevention.
      Respondents rarely said they appraised the methods and content of trials, rather
      they judged the trustworthiness of the source of trial evidence and interpreted
      it within the context of the economic and social factors which impinge on their
      practice. Moreover, trial data become relevant for routine practice only when
      underpinned by a consensus on these issues. CONCLUSION: Strategies to promote
      incorporation of evidence from clinical trials into everyday practice are likely
      to be effective if they tap into and build on the process of local consensus
      building. Strategies such as teaching critical appraisal skills and guideline
      development may have little effect if they are separated from this process.

PMID- 9784450
TI  - Implications of applying widely accepted cholesterol screening and management
      guidelines to a British adult population: cross sectional study of cardiovascular
      disease and risk factors.
AB  - OBJECTIVE: To compare the implications of four widely used cholesterol screening
      and treatment guidelines by applying them to a population in the United Kingdom.
      DESIGN: Guidelines were applied to population based data from a cross sectional
      study of cardiovascular disease and risk factors. SETTING: Newcastle upon Tyne,
      United Kingdom. SUBJECTS: General population sample (predominantly of European
      origin) of 322 men and 319 women aged 25-64 years. MAIN OUTCOME MEASURES:
      Proportions recommended for screening and treatment. METHODS: Criteria from the
      British Hyperlipidaemia Association, the British Drugs and Therapeutics Bulletin
      (which used the Sheffield table), the European Atherosclerosis Society, and the
      American national cholesterol education programme were applied to the population.
      RESULTS: Proportions recommended for treatment varied appreciably. Based on the
      British Drugs and Therapeutics Bulletin guidelines, treatment was recommended for
      5.3% (95% confidence interval 2.9% to 7.7%) of men and 3.3% (1.5% to 5.3%) of
      women, while equivalent respective values were 4.6 (2.3 to 6.9) and 2.8 (1.0 to
      4.6) for the British Hyperlipidaemia Association, 23% (18.4% to 27.6%) and 10.6%
      (7.3% to 14.0%) for the European Atherosclerosis Society, and 37.2% (31.9% to
      42.5%) and 22.2% (17.6% to 26.8%) for the national cholesterol education
      programme. Only the British Hyperlipidaemia Association and Drugs and
      Therapeutics Bulletin guidelines recommend selective screening. Applying British
      Hyperlipidaemia Association guidelines, from 7.1% (4.3% to 9.9%) of men in level
      one to 56.7% (51.3% to 62.1%) of men in level three, and from 4.4% (2.1% to 6.7%)
      of women in level one to 54.4% (48.9% to 59.9%) of women in level three would
      have been recommended for cholesterol screening. Had the Drugs and Therapeutics
      Bulletin guidelines been applied, 22.2% (16.5% to 27.9%) of men and 12.2% (8. 6%
      to 15.8%) of women would have been screened. CONCLUSIONS: Without evidence based
      guidelines, there are problems of variation. A consistent approach needs to be
      developed and agreed across the United Kingdom.

PMID- 9784453
TI  - All in a day's work 

PMID- 9784454
TI  - Good advice 

PMID- 9784455
TI  - Magic bullet for obesity.

PMID- 9784457
TI  - Scented women 

PMID- 9784456
TI  - Methaemoglobinaemia associated with sodium nitrite in three siblings.

PMID- 9784458
TI  - Hyperbaric oxygen therapy.

PMID- 9784459
TI  - The Wisheart affair: paediatric cardiological services in Bristol, 1990-5.

PMID- 9784460
TI  - Professional self respect: rights and responsibilities in the new NHS.

PMID- 9784461
TI  - The milkman of human kindness 

PMID- 9784462
TI  - Select medical students.

PMID- 9784463
TI  - Bayesians and frequentists.

PMID- 9784464
TI  - Guidelines for cervical screening await scientific evaluation.

PMID- 9784465
TI  - Secondary prevention in acute myocardial infarction. Data cited from two studies
      were inaccurate.

PMID- 9784467
TI  - Health needs assessment is not required for priority setting.

PMID- 9784466
TI  - Acute excited states and sudden death.

PMID- 9784468
TI  - Insider view of rationing down under.

PMID- 9784469
TI  - How should different life expectancies be valued? Existential model may be better
      than scale that uses quality adjusted life years.

PMID- 9784470
TI  - When can odds ratios mislead? Odds ratios should be used only in case-control
      studies and logistic regression analyses.

PMID- 9784471
TI  - Long term pharmacotherapy of depression. Tricyclic antidepressants should not be
      first line treatment.

PMID- 9784472
TI  - Admissions for depression have not increased among men in Republic of Ireland.

PMID- 9784473
TI  - Doctors who do not feel sober enough to drive should avoid helping in medical
      emergencies.

PMID- 9784474
TI  - Donald barrie case 

PMID- 9784475
TI  - Northern ireland GPs complain of stress and workload 

PMID- 9784476
TI  - The new dictionary of medical ethics 

PMID- 9784477
TI  - Thelonious monk: his life and music 

PMID- 9784478
TI  - Communications skills version 1:2 

PMID- 9784479
TI  - Website of the week 

PMID- 9784480
TI  - When big may not be beautiful 

PMID- 9784482
TI  - Thelonious monk website 

PMID- 9784481
TI  - One's own petard 

PMID- 9784484
TI  - Reducing exposure to house dust mite allergen does not improve asthma 

PMID- 9784483
TI  - From selection to revalidation 

PMID- 9784485
TI  - Women are advantaged and ethnic minorities disadvantaged in medical school
      selection 

PMID- 9784486
TI  - Childhood fractures don't often cause bruising 

PMID- 9784487
TI  - Use of lipid lowering drugs in primary care is highly variable 

PMID- 9784488
TI  - WAT-free mice: diabetes without obesity 

PMID- 9784489
TI  - Orphan nuclear receptors--new ligands and new possibilities.

PMID- 9784490
TI  - Fgf-10 is required for both limb and lung development and exhibits striking
      functional similarity to Drosophila branchless.
AB  - Fgf-10-deficient mice (Fgf-10(-/-)) were generated to determine the role(s) of
      Fgf-10 in vertebrate development. Limb bud initiation was abolished in Fgf-10(-/
      ) mice. Strikingly, Fgf-10(-/-) fetuses continued to develop until birth, despite
      the complete absence of both fore- and hindlimbs. Fgf-10 is necessary for apical
      ectodermal ridge (AER) formation and acts epistatically upstream of Fgf-8, the
      earliest known AER marker in mice. Fgf-10(-/-) mice exhibited perinatal lethality
      associated with complete absence of lungs. Although tracheal development was
      normal, main-stem bronchial formation, as well as all subsequent pulmonary
      branching morphogenesis, was completely disrupted. The pulmonary phenotype of Fgf
      10(-/-) mice is strikingly similar to that of the Drosophila mutant branchless,
      an Fgf homolog.

PMID- 9784491
TI  - Cooperation between the Cdk inhibitors p27(KIP1) and p57(KIP2) in the control of
      tissue growth and development.
AB  - Cell cycle exit is required for terminal differentiation of many cell types. The
      retinoblastoma protein Rb has been implicated both in cell cycle exit and
      differentiation in several tissues. Rb is negatively regulated by cyclin
      dependent kinases (Cdks). The main effectors that down-regulate Cdk activity to
      activate Rb are not known in the lens or other tissues. In this study, using
      multiple mutant mice, we show that the Cdk inhibitors p27(KIP1) and p57(KIP2)
      function redundantly to control cell cycle exit and differentiation of lens fiber
      cells and placental trophoblasts. These studies demonstrate that p27(KIP1) and
      p57(KIP2) are critical terminal effectors of signal transduction pathways that
      control cell differentiation.

PMID- 9784492
TI  - Life without white fat: a transgenic mouse.
AB  - We have generated a transgenic mouse with no white fat tissue throughout life.
      These mice express a dominant-negative protein, termed A-ZIP/F, under the control
      of the adipose-specific aP2 enhancer/promoter. This protein prevents the DNA
      binding of B-ZIP transcription factors of both the C/EBP and Jun families. The
      transgenic mice (named A-ZIP/F-1) have no white adipose tissue and dramatically
      reduced amounts of brown adipose tissue, which is inactive. They are initially
      growth delayed, but by week 12, surpass their littermates in weight. The mice
      eat, drink, and urinate copiously, have decreased fecundity, premature death, and
      frequently die after anesthesia. The physiological consequences of having no
      white fat tissue are profound. The liver is engorged with lipid, and the internal
      organs are enlarged. The mice are diabetic, with reduced leptin (20-fold) and
      elevated serum glucose (3-fold), insulin (50- to 400-fold), free fatty acids (2
      fold), and triglycerides (3- to 5-fold). The A-ZIP/F-1 phenotype suggests a mouse
      model for the human disease lipoatrophic diabetes (Seip-Berardinelli syndrome),
      indicating that the lack of fat can cause diabetes. The myriad of consequences of
      having no fat throughout development can be addressed with this model.

PMID- 9784493
TI  - Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear
      SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy.
AB  - Overexpression of the nuclear form of sterol regulatory element-binding protein
      1c (nSREBP-1c/ADD1) in cultured 3T3-L1 preadipocytes was shown previously to
      promote adipocyte differentiation. Here, we produced transgenic mice that
      overexpress nSREBP-1c in adipose tissue under the control of the adipocyte
      specific aP2 enhancer/promoter. A syndrome with the following features was
      observed: (1) Disordered differentiation of adipose tissue. White fat failed to
      differentiate fully, and the size of white fat depots was markedly decreased.
      Brown fat was hypertrophic and contained fat-laden cells resembling immature
      white fat. Levels of mRNA encoding adipocyte differentiation markers (C/EBPalpha,
      PPARgamma, adipsin, leptin, UCP1) were reduced, but levels of Pref-1 and TNFalpha
      were increased. (2) Marked insulin resistance with 60-fold elevation in plasma
      insulin. (3) Diabetes mellitus with elevated blood glucose (>300 mg/dl) that
      failed to decline when insulin was injected. (4) Fatty liver from birth and
      elevated plasma triglyceride levels later in life. These mice exhibit many of the
      features of congenital generalized lipodystrophy (CGL), an autosomal recessive
      disorder in humans.

PMID- 9784495
TI  - Inorganic pyrophosphatase is a component of the Drosophila nucleosome remodeling
      factor complex.
AB  - The Drosophila nucleosome remodeling factor (NURF) is a protein complex
      consisting of four polypeptides that facilitates the perturbation of chromatin
      structure in vitro in an ATP-dependent manner. The 140-kD NURF subunit, imitation
      switch (ISWI), is related to the SWI2/SNF2 ATPase. Another subunit, NURF-55, is a
      55-kD WD repeat protein homologous to the human retinoblastoma-associated protein
      RbAp48. Here, we report the cloning and characterization of the smallest (38 kD)
      component of NURF. NURF-38 is strikingly homologous to known inorganic
      pyrophosphatases. Both recombinant NURF-38 alone and the purified NURF complex
      are shown to have inorganic pyrophosphatase activity. Inhibition of the
      pyrophosphatase activity of NURF with sodium fluoride has no significant effect
      on chromatin remodeling, indicating that these two activities may be
      biochemically uncoupled. Our results suggest that NURF-38 may serve a structural
      or regulatory role in the complex. Alternatively, because accumulation of
      unhydrolyzed pyrophosphate during nucleotide incorporation inhibits
      polymerization, NURF may also have been adapted to deliver pyrophosphatase to
      chromatin to assist in replication or transcription by efficient removal of the
      inhibitory metabolite.

PMID- 9784494
TI  - SXR, a novel steroid and xenobiotic-sensing nuclear receptor.
AB  - An important requirement for physiologic homeostasis is the detoxification and
      removal of endogenous hormones and xenobiotic compounds with biological activity.
      Much of the detoxification is performed by cytochrome P-450 enzymes, many of
      which have broad substrate specificity and are inducible by hundreds of different
      compounds, including steroids. The ingestion of dietary steroids and lipids
      induces the same enzymes; therefore, they would appear to be integrated into a
      coordinated metabolic pathway. Instead of possessing hundreds of receptors, one
      for each inducing compound, we propose the existence of a few broad specificity,
      low-affinity sensing receptors that would monitor aggregate levels of inducers to
      trigger production of metabolizing enzymes. In support of this model, we have
      isolated a novel nuclear receptor, termed the steroid and xenobiotic receptor
      (SXR), which activates transcription in response to a diversity of natural and
      synthetic compounds. SXR forms a heterodimer with RXR that can bind to and induce
      transcription from response elements present in steroid-inducible cytochrome P
      450 genes and is expressed in tissues in which these catabolic enzymes are
      expressed. These results strongly support the steroid sensor hypothesis and
      suggest that broad specificity sensing receptors may represent a novel branch of
      the nuclear receptor superfamily.

PMID- 9784496
TI  - WT1 interacts with the splicing factor U2AF65 in an isoform-dependent manner and
      can be incorporated into spliceosomes.
AB  - WT1 is essential for normal kidney development, and genetic alterations are
      associated with Wilms' tumor, Denys Drash (DDS), and Frasier syndromes. Although
      generally considered a transcription factor this study has revealed that WT1
      interacts with an essential splicing factor, U2AF65, and associates with the
      splicing machinery. WT1 is alternatively spliced and isoforms that include three
      amino acids, KTS, show stronger interaction with U2AF65 in vitro and better
      colocalization with splicing factors in vivo. Interestingly a mutation associated
      with DDS enhanced both -KTS WT1 binding to U2AF65 and splicing-factor
      colocalization. These data illustrate the functional importance of WT1 isoforms
      and suggest that WT1 plays a role in pre-mRNA splicing.

PMID- 9784497
TI  - mRNA stabilization by poly(A) binding protein is independent of poly(A) and
      requires translation.
AB  - Translation and mRNA stability are enhanced by the presence of a poly(A) tail. In
      vivo, the tail interacts with a conserved polypeptide, poly(A) binding protein
      (Pab1p). To examine Pab1p function in vivo, we have tethered Pab1p to the 3' UTR
      of reporter mRNAs by fusing it to MS2 coat protein and placing MS2 binding sites
      in the 3' UTR of the reporter. This strategy allows us to uncouple Pab1p function
      from its RNA binding activity. We show that mRNAs that lack a poly(A) tail in
      vivo are stabilized by Pab1p, and that the portions of Pab1p required for
      stabilization are genetically distinct from those required for poly(A) binding.
      In addition, stabilization by Pab1p requires ongoing translation of the mRNA. We
      conclude that the primary, or sole, function of poly(A) with respect to mRNA
      stability is simply to bring Pab1p to the mRNA, and that mRNA stabilization is an
      intrinsic property of Pab1p. The approach we describe may be useful in
      identifying and assaying 3' UTR regulatory proteins, as it uncouples analysis of
      function from RNA binding.

PMID- 9784498
TI  - HSP101 functions as a specific translational regulatory protein whose activity is
      regulated by nutrient status.
AB  - The 5' leader (Omega) of tobacco mosaic viral RNA functions as a translational
      enhancer. Sequence analysis of a 102-kD protein, identified previously as a
      specific Omega RNA-binding protein, revealed homology to the HSP101/HSP104/ClpB
      family of heat shock proteins and its expression in yeast complemented a
      thermotolerance defect caused by a deletion of the HSP104 gene. Up to a 50-fold
      increase in the translation of Omega-luc, but not luc mRNA was observed in yeast
      expressing the tobacco HSP101 whereas Omega failed to enhance translation in the
      absence of HSP101. Therefore, HSP101 and Omega comprise a two-component
      translational regulatory mechanism that can be recapitulated in yeast. Analysis
      of HSP101 function in yeast translation mutants suggested that the initiation
      factor (eIF) 3 and specifically one (TIF4632) of the two eIF4G proteins were
      required for the HSP101-mediated enhancement. The RNA-binding and translational
      regulatory activities of HSP101 were inactive in respiring cells or in cells
      subject to nutrient limitation, but its thermotolerance function remained
      unaffected. This is the first identification of a protein required for specific
      translational enhancement of capped mRNAs, the first report of a translational
      regulatory function for any heat-shock protein, and the first functional
      distinction between the two eIF4G proteins present in eukaryotes.

PMID- 9784499
TI  - Drosophila unpaired encodes a secreted protein that activates the JAK signaling
      pathway.
AB  - In vertebrates, many cytokines and growth factors have been identified as
      activators of the JAK/STAT signaling pathway. In Drosophila, JAK and STAT
      molecules have been isolated, but no ligands or receptors capable of activating
      the pathway have been described. We have characterized the unpaired (upd) gene,
      which displays the same distinctive embryonic mutant defects as mutations in the
      Drosophila JAK (hopscotch) and STAT (stat92E) genes. Upd is a secreted protein,
      associated with the extracellular matrix, that activates the JAK pathway. We
      propose that Upd is a ligand that relies on JAK signaling to stimulate
      transcription of pair-rule genes in a segmentally restricted manner in the early
      Drosophila embryo.

PMID- 9784500
TI  - Development of neuroendocrine lineages requires the bHLH-PAS transcription factor
      SIM1.
AB  - The bHLH-PAS transcription factor SIM1 is expressed during the development of the
      hypothalamic-pituitary axis in three hypothalamic nuclei: the paraventricular
      nucleus (PVN), the anterior periventricular nucleus (aPV), and the supraoptic
      nucleus (SON). To investigate Sim1 function in the hypothalamus, we produced mice
      carrying a null allele of Sim1 by gene targeting. Homozygous mutant mice die
      shortly after birth. Histological analysis shows that the PVN and the SON of
      these mice are hypocellular. At least five distinct types of secretory neurons,
      identified by the expression of oxytocin, vasopressin, thyrotropin-releasing
      hormone, corticotropin-releasing hormone, and somatostatin, are absent in the
      mutant PVN, aPV, and SON. Moreover, we show that SIM1 controls the development of
      these secretory neurons at the final stages of their differentiation. A subset of
      these neuronal lineages in the PVN/SON are also missing in mice bearing a
      mutation in the POU transcription factor BRN2. We provide evidence that, during
      development of the Sim1 mutant hypothalamus, the prospective PVN/SON region fails
      to express Brn2. Our results strongly indicate that SIM1 functions upstream to
      maintain Brn2 expression, which in turn directs the terminal differentiation of
      specific neuroendocrine lineages within the PVN/SON.

PMID- 9784501
TI  - A surface of Escherichia coli sigma 70 required for promoter function and
      antitermination by phage lambda Q protein.
AB  - The sigma initiation factor sigma70 of Escherichia coli acts not only in promoter
      recognition and DNA strand opening, but also to mediate the transformation of RNA
      polymerase (RNAP) to an antiterminating form by the phage lambda gene Q protein.
      Q is able to bind and modify RNAP when alpha70, still present in the initially
      elongating enzyme, recognizes a repeat of the -10 promoter element and induces a
      transcription pause. We have isolated mutations in the rpoD gene for sigma70 that
      impair Q function because they reduce the ability of sigma70 to recognize the
      downstream pause site. These mutations identify a locus of sigma70 that is
      important for the formation and stability of open promoter complex, likely
      because it mediates protein interactions with RNAP core.

PMID- 9784502
TI  - Specific telomerase RNA residues distant from the template are essential for
      telomerase function.
AB  - The reverse transcriptase telomerase is a ribonucleoprotein complex that adds
      telomeric repeats to chromosome ends, using a sequence within its endogenous RNA
      component as a template. Although templating domains of telomerase RNA have been
      studied in detail, little is known about the roles of the remaining residues,
      particularly in yeast. We examined the functions of nontemplate telomerase
      residues in the telomerase RNA of budding yeast Kluyveromyces lactis. Although
      approximately half of the RNA residues were dispensable for function, four
      specific regions were essential for telomerase action in vivo. We analyzed the
      effects of mutating these regions on in vivo function, in vitro telomerase
      activity, and telomerase RNP assembly. Deletion of two regions resulted in
      synthesis of stable RNAs that appeared unable to assemble into a stable RNP.
      Mutating a region near the 5' end of the RNA allowed RNP assembly but abolished
      enzymatic activity. Mutations in another specific small region of the RNA led to
      an inactive telomerase RNP with an altered RNA conformation.

PMID- 9784503
TI  - Antigenic diversity and gene polymorphisms in Haemophilus influenzae.

PMID- 9784504
TI  - Helicobacter pylori containing only cytoplasmic urease is susceptible to acid.
AB  - Helicobacter pylori, an important etiologic agent in a variety of gastroduodenal
      diseases, produces large amounts of urease as an essential colonization factor.
      We have demonstrated previously that urease is located within the cytoplasm and
      on the surface of H. pylori both in vivo and in stationary-phase culture. The
      purpose of the present study was to assess the relative contributions of
      cytoplasmic and surface-localized urease to the ability of H. pylori to survive
      exposure to acid in the presence of urea. Toward this end, we compared the acid
      resistance in vitro of H. pylori cells which possessed only cytoplasmic urease to
      that of bacteria which possessed both cytoplasmic and surface-localized or
      extracellular urease. Bacteria with only cytoplasmic urease activity were
      generated by using freshly subcultured bacteria or by treating repeatedly
      subcultured H. pylori with flurofamide (1 microM), a potent, but poorly
      diffusible urease inhibitor. H. pylori with cytoplasmic and surface-located
      urease activity survived in an acid environment when 5 mM urea was present. In
      contrast, H. pylori with only cytoplasmic urease shows significantly reduced
      survival when exposed to acid in the presence of 5 mM urea. Similarly,
      Escherichia coli SE5000 expressing H. pylori urease and the Ni2+ transport
      protein NixA, which expresses cytoplasmic urease activity at levels similar to
      those in wild-type H. pylori, survived minimally when exposed to acid in the
      presence of 5 to 50 mM urea. We conclude that cytoplasmic urease activity alone
      is not sufficient (although cytoplasmic urease activity is likely to be
      necessary) to allow survival of H. pylori in acid; the activity of surface
      localized urease is essential for resistance of H. pylori to acid under the assay
      conditions used. Therefore, the mechanism whereby urease becomes associated with
      the surface of H. pylori, which involves release of the enzyme from bacteria due
      to autolysis followed by adsorption of the enzyme to the surface of intact
      bacteria ("altruistic autolysis"), is essential for survival of H. pylori in an
      acid environment. The ability of H. pylori to survive exposure to low pH is
      likely to depend on a combination of both cytoplasmic and surface-associated
      urease activities.

PMID- 9784505
TI  - A Chlamydia pneumoniae component that induces macrophage foam cell formation is
      chlamydial lipopolysaccharide.
AB  - Chlamydia pneumoniae infection is associated with atherosclerotic heart and
      vessel disease, but a causal relationship between this pathogen and the disease
      process has not been established. Recently, it was reported that C. pneumoniae
      induces human macrophage foam cell formation, a key event in early atheroma
      development, suggesting a role for the organism in atherogenesis. This study
      further examines C. pneumoniae-induced foam cell formation in the murine
      macrophage cell line RAW-264.7. Infected RAW cells accumulated cholesteryl esters
      when cultured in the presence of low-density lipoprotein in a manner similar to
      that described for human macrophages. Exposure of C. pneumoniae elementary bodies
      to periodate, but not elevated temperatures, inhibited cholesteryl ester
      accumulation, suggesting a role for chlamydial lipopolysaccharide (cLPS) in
      macrophage foam cell formation. Purified cLPS was found to be sufficient to
      induce cholesteryl ester accumulation and foam cell formation. Furthermore, the
      LPS antagonist lipid X inhibited C. pneumoniae and cLPS-induced lipid uptake.
      These data indicate that cLPS is a C. pneumoniae component that induces
      macrophage foam cell formation and suggest that infected macrophages chronically
      exposed to cLPS may accumulate excess cholesterol to contribute to atheroma
      development.

PMID- 9784507
TI  - Staphylococcal enterotoxin B primes cytokine secretion and lytic activity in
      response to native bacterial antigens.
AB  - Superantigens stimulate T-lymphocyte proliferation and cytokine production, but
      the effects of superantigen exposure on cell function within a complex, highly
      regulated immune response remain to be determined. In this study, we demonstrate
      that superantigen exposure significantly alters the murine host response to
      bacterial antigens in an in vitro coculture system. Two days after exposure to
      the superantigen staphylococcal enterotoxin B, splenocytes cultured with
      Streptococcus mutans produced significantly greater amounts of gamma interferon
      (IFN-gamma) and interleukin-12 than did sham-injected controls. The majority of
      IFN-gamma production appeared to be CD8(+) T-cell derived since depletion of this
      cell type dramatically reduced the levels of IFN-gamma. To study host cell damage
      that may occur following superantigen exposure, we analyzed cytotoxicity to
      "bystander" fibroblast cells cultured with splenocytes in the presence of
      bacterial antigens. Prior host exposure to staphylococcal enterotoxin B
      significantly enhanced fibroblast cytotoxicity in the presence of bacteria.
      Neutralization of IFN-gamma decreased the amount of cytotoxicity observed.
      However, a greater reduction was evident when splenocyte-bacterium cocultures
      were separated from the bystander cell monolayer via a permeable membrane
      support. Increased cytotoxicity appears to be primarily dependent upon cell-cell
      contact. Collectively, these data indicate that overproduction of inflammatory
      cytokines may alter the activity of cytotoxic immune cells. Superantigen exposure
      exacerbates cytokine production and lytic cell activity when immune cells
      encounter bacteria in vitro and comparable activities could possibly occur in
      vivo.

PMID- 9784506
TI  - Vaccination with trypomastigote surface antigen 1-encoding plasmid DNA confers
      protection against lethal Trypanosoma cruzi infection.
AB  - DNA vaccination was evaluated with the experimental murine model of Trypanosoma
      cruzi infection as a means to induce antiparasite protective immunity, and the
      trypomastigote surface antigen 1 (TSA-1), a target of anti-T. cruzi antibody and
      major histocompatibility complex (MHC) class I-restricted CD8(+) cytotoxic T
      lymphocyte (CTL) responses, was used as the model antigen. Following the
      intramuscular immunization of H-2(b) and H-2(d) mice with a plasmid DNA encoding
      an N-terminally truncated TSA-1 lacking or containing the C-terminal nonapeptide
      tandem repeats, the antibody level, CTL response, and protection against
      challenge with T. cruzi were assessed. In H-2(b) mice, antiparasite antibodies
      were induced only by immunization with the DNA construct encoding TSA-1
      containing the C-terminal repeats. However, both DNA constructs were efficient in
      eliciting long-lasting CTL responses against the protective H-2Kb-restricted TSA
      1515-522 epitope. In H-2(d) mice, inoculation with either of the two TSA-1
      expressing vectors effectively generated antiparasite antibodies and primed CTLs
      that lysed T. cruzi-infected cells in an antigen-specific, MHC class I
      restricted, and CD8(+)-T-cell-dependent manner. When TSA-1 DNA-vaccinated animals
      were challenged with T. cruzi, 14 of 22 (64%) H-2(b) and 16 of 18 (89%) H-2(d)
      mice survived the infection. The ability to induce significant murine anti-T.
      cruzi protective immunity by immunization with plasmid DNA expressing TSA-1
      provides the basis for the application of this technology in the design of
      optimal DNA multicomponent anti-T. cruzi vaccines which may ultimately be used
      for the prevention or treatment of Chagas' disease.

PMID- 9784508
TI  - Expression of CD14 by hepatocytes: upregulation by cytokines during endotoxemia.
AB  - Studies were undertaken to examine hepatocyte CD14 expression during endotoxemia.
      Our results show that lipopolysaccharide (LPS) treatment in vivo caused a marked
      upregulation in CD14 mRNA and protein levels in rat hepatocytes. Detectable
      increases in mRNA were seen as early as 1.5 h after LPS treatment; these
      increases peaked at 20-fold by 3 h and returned to baseline levels by 24 h. In
      situ hybridization localized the CD14 mRNA expression to hepatocytes both in
      vitro and in vivo. Increases in hepatic CD14 protein levels were detectable by 3
      h and peaked at 12 h. Hepatocytes from LPS-treated animals expressed greater
      amounts of cell-associated CD14 protein, and more of the soluble CD14 was
      released by hepatocytes from LPS-treated rats in vitro. The increases in
      hepatocyte CD14 expression during endotoxemia occurred in parallel to increases
      of CD14 levels in plasma. To provide molecular identification of the hepatocyte
      CD14, we cloned the rat liver CD14 cDNA. The longest clone consists of a 1,591-bp
      insert containing a 1,116-bp open reading frame. The deduced amino acid sequence
      is 372 amino acids long, has 81.8 and 62.8% homology to the amino acid sequences
      of mouse and human CD14, respectively, and is identical to the rat macrophage
      CD14. The expressed CD14 protein from this clone was functional, as indicated by
      NF-kappaB activation in response to LPS and fluorescein isothiocyanate-LPS
      binding in CHO cells stably transfected with rat CD14. A nuclear run-on assay
      showed that CD14 transcription rates were significantly increased in hepatocytes
      from LPS-treated animals, indicating that the upregulation in CD14 mRNA levels
      observed in rat hepatocytes after LPS treatment is dependent, in part, on
      increased transcription. In vitro and in vivo experiments indicated that
      interleukin-1beta and/or tumor necrosis factor alpha participate in the
      upregulation of CD14 mRNA levels in hepatocytes. Our data indicate that
      hepatocytes express CD14 and that hepatocyte CD14 mRNA and protein levels
      increase rapidly during endotoxemia. Our observations also support the idea that
      soluble CD14 is an acute-phase protein and that hepatocytes could be a source for
      soluble CD14 production.

PMID- 9784510
TI  - New scavenger receptor-like receptors for the binding of lipopolysaccharide to
      liver endothelial and Kupffer cells.
AB  - Lipopolysaccharide (LPS) is cleared from the blood mainly by the liver. The
      Kupffer cells are primarily responsible for this clearance; liver endothelial and
      parenchymal cells contribute to a lesser extent. Although several binding sites
      have been described, only CD14 is known to be involved in LPS signalling. Among
      the other LPS binding sites that have been identified are scavenger receptors.
      Scavenger receptor class A (SR-A) types I and II are expressed in the liver on
      endothelial cells and Kupffer cells, and a 95-kDa receptor, identified as
      macrosialin, is expressed on Kupffer cells. In this study, we examined the role
      of scavenger receptors in the binding of LPS by the liver in vivo and in vitro.
      Fucoidin, a scavenger receptor ligand, significantly reduced the clearance of
      125I-LPS from the serum and decreased the liver uptake of 125I-LPS about 40%.
      Within the liver, the in vivo binding of 125I-LPS to Kupffer and liver
      endothelial cells was decreased 72 and 71%, respectively, while the binding of
      125I-LPS to liver parenchymal cells increased 34% upon fucoidin preinjection.
      Poly(I) inhibited the binding of 125I-LPS to Kupffer and endothelial cells in
      vitro 73 and 78%, respectively, while poly(A) had no effect. LPS inhibited the
      binding of acetylated low-density lipoprotein (acLDL) to Kupffer and liver
      endothelial cells 40 and 55%, respectively, and the binding of oxidized LDL
      (oxLDL) to Kupffer and liver endothelial cells 65 and 61%, respectively. oxLDL
      and acLDL did not significantly inhibit the binding of LPS to these cells. We
      conclude that on both endothelial cells and Kupffer cells, LPS binds mainly to
      scavenger receptors, but SR-A and macrosialin contribute to a limited extent to
      the binding of LPS.

PMID- 9784511
TI  - Local immune responses to Chlamydia pneumoniae in the lungs of BALB/c mice during
      primary infection and reinfection.
AB  - Cell-mediated immune (CMI) responses play a major role in protection as well as
      pathogenesis of many intracellular bacterial infections. In this study, we
      evaluated the infection kinetics and assessed histologically the lymphoid
      reactions and local, in vitro-restimulated CMI responses in lungs of BALB/c mice,
      during both primary infection and reinfection with Chlamydia pneumoniae. The
      primary challenge resulted in a self-restricted infection with elimination of
      culturable bacteria by day 27 after challenge. A mild lymphoid reaction
      characterized the pathology in the lungs. In vitro CMI responses consisted of a
      weak proliferative response and no secretion of gamma interferon (IFN-gamma). The
      number of lung-derived mononuclear cells increased substantially during the
      primary infection; the largest relative increase was observed in B cells
      (B220(+)). After reinfection, the number of lung-derived mononuclear cells
      increased further, and the response consisted mainly of T cells. The reinfection
      was characterized in vivo by significant protection from infection (fewer
      cultivable bacteria in the lungs for a shorter period of time) but increased
      local lymphoid reaction at the infection site. In vitro, as opposed to the
      response in naive mice, acquired immunity was characterized by a strongly Th1
      biased (IFN-gamma) CMI response. These results suggest that repeated infections
      with C. pneumoniae may induce Th1-type responses with similar associated tissue
      reactions, as shown in C. trachomatis infection models.

PMID- 9784509
TI  - Novel selection for isoniazid (INH) resistance genes supports a role for NAD+
      binding proteins in mycobacterial INH resistance.
AB  - The genetic basis of isoniazid (INH) resistance remains unknown for a significant
      proportion of clinical isolates. To identify genes which might confer resistance
      by detoxifying or sequestering INH, we transformed the Escherichia coli oxyR
      mutant, which is relatively sensitive to INH, with a Mycobacterium tuberculosis
      plasmid library and selected for INH-resistant clones. Three genes were
      identified and called ceo for their ability to complement the Escherichia coli
      oxyR mutant. ceoA was the previously identified M. tuberculosis glf gene, which
      encodes a 399-amino-acid NAD+- and flavin adenine dinucleotide-requiring enzyme
      responsible for catalyzing the conversion of UDP-galactopyranose to UDP
      galactofuranose. The proteins encoded by the ceoBC pair were homologous with one
      another and with the N terminus of the potassium uptake regulatory protein TrkA.
      Each of the three Ceo proteins contains a motif common to NAD+ binding pockets.
      Overexpression of the M. tuberculosis glf gene by placing it under the control of
      the hsp60 promoter on a multicopy plasmid in Mycobacterium bovis BCG produced a
      strain for which the INH MIC was increased 50% compared to that for the control
      strains, while similar overexpression of the ceoBC pair had no effect on INH
      susceptibility in BCG. Mycobacterial extracts containing the overexpressed Glf
      protein did not bind radiolabeled INH directly, suggesting a more complex
      mechanism than the binding of unmodified INH. Our results support the hypothesis
      that upregulated mycobacterial proteins such as Glf may contribute to INH
      resistance in M. tuberculosis by binding a modified form of INH or by
      sequestering a factor such as NAD+ required for INH activity.

PMID- 9784512
TI  - Differential expression of Borrelia burgdorferi proteins during growth in vitro.
AB  - In an earlier paper we described the transcriptionally regulated differential
      levels of expression of two lipoproteins of Borrelia burgdorferi, P35 and P7.5,
      during growth of the spirochetes in culture from logarithmic phase to stationary
      phase (K. J. Indest, R. Ramamoorthy, M. Sole, R. D. Gilmore, B. J. B. Johnson,
      and M. T. Philipp, Infect. Immun. 65:1165-1171, 1997). Here we further assess
      this phenomenon by investigating whether the expression of other antigens of B.
      burgdorferi, including some well-characterized ones, are also regulated in a
      growth-phase-dependent manner in vitro. These studies revealed 13 additional
      antigens, including OspC, BmpD, and GroEL, that were upregulated 2- to 66-fold
      and a 28-kDa protein that was downregulated 2- to 10-fold, during the interval
      between the logarithmic- and stationary-growth phases. Unlike with these in vitro
      regulated proteins, the levels of expression of OspA, OspB, P72, flagellin, and
      BmpA remained unchanged throughout growth of the spirochetes in culture.
      Furthermore, ospAB, bmpAB, groEL, and fla all exhibited similar mRNA profiles,
      which is consistent with the constitutive expression of these genes. By contrast,
      the mRNA and protein profiles of ospC and bmpD indicated regulated expression of
      these genes. While bmpD exhibited a spike in mRNA expression in early stationary
      phase, ospC maintained a relatively higher level of mRNA throughout culture.
      These findings demonstrate that there are additional genes besides P7.5 and P35
      whose regulated expression can be investigated in vitro and which may thus serve
      as models to facilitate the study of regulatory mechanisms in an organism that
      cycles between an arthropod and a vertebrate host.

PMID- 9784514
TI  - Differential growth characteristics and streptomycin susceptibility of virulent
      and avirulent Mycobacterium tuberculosis strains in a novel fibroblast
      mycobacterium microcolony assay.
AB  - The ability to spread from cell to cell may be an important virulence determinant
      of Mycobacterium tuberculosis. An in vitro assay was developed to characterize
      this ability among four strains of M. tuberculosis: the attenuated strain H37Ra,
      the virulent strains H37Rv and Erdman, and a virulent clinical isolate (Stew).
      Confluent monolayers of human skin fibroblasts were infected with these strains
      and overlaid with agar-medium. M. tuberculosis infection developed over 21 days
      as microcolonies originating within the plane of the fibroblasts. Microcolonies
      of the virulent strains had an elongated appearance and exhibited extensive
      cording. The cords appeared to invade adjacent cells within the plane of the
      monolayer. Microcolony diameter of the Erdman strain was significantly larger
      than that of the other virulent strains, indicating that virulent strains can
      have distinguishing phenotypes in this assay. In contrast, avirulent H37Ra
      microcolonies were rounded and noncorded. H37Ra microcolonies were significantly
      smaller than those of the virulent strains. Microcolony diameter of the virulent
      strains was not reduced by the extracellularly acting antibiotic streptomycin at
      concentrations of up to 5.0 microgram/ml. In contrast, H37Ra microcolony size was
      reduced at concentrations as low as 0.5 microgram/ml. Growth of all strains was
      similarly inhibited by 1.0 microgram of streptomycin per ml in fibroblast
      conditioned tissue culture medium alone. When fibroblasts were infected with the
      M. tuberculosis strains without an agar overlay, with and without streptomycin,
      numbers of CFU mirrored the changes observed in the microcolony assay. There was
      a statistically significant decrease in H37Ra CFU compared to virulent strains
      after treatment with streptomycin. These differences between H37Ra and virulent
      strains in human fibroblasts suggest that H37Ra may be lacking a virulence
      determinant involved in cell-to-cell spread of M. tuberculosis.

PMID- 9784513
TI  - Activation of Rho GTPases by Escherichia coli cytotoxic necrotizing factor 1
      increases intestinal permeability in Caco-2 cells.
AB  - The cytotoxic necrotizing factor 1 (CNF1) activates Rho GTPases by deamidation of
      glutamine-63 and thereby induces redistribution of the actin cytoskeleton and
      formation of stress fibers. Here, we have studied the effects of CNF1 on the
      transepithelial resistance of Caco-2 cells, a human intestinal epithelial cell
      line, in comparison with the Rho-inactivating toxin B of Clostridium difficile.
      Whereas toxin B decreased the transepithelial resistance of Caco-2 cells by about
      80% after 4 h, CNF1 reduced it by about 40%. Significant changes of the
      transepithelial resistance induced by CNF1 were detected after 3 h of incubation.
      Half-maximal effects were observed with 10 and 41 ng of CNF1 and toxin B per ml,
      respectively. Flux measurement revealed no CNF1-induced increase of fluorescein
      isothiocyanate-dextran permeation within the first 4 h of incubation and a 2.9
      fold increase after 24 h of incubation. In contrast, toxin B induced a 28-fold
      increase of permeation after 24 h. As detected by rhodamine-phalloidin staining,
      CNF1 increased polymerization of F actin at focal contacts of adjacent cells and
      induced formation of stress fibers. The data indicate that not only
      depolymerization but also polymerization of actin and subsequent reorganization
      of the actin cytoskeleton alter the barrier function of intestinal tight
      junctions.

PMID- 9784515
TI  - 5-Lipoxygenase reaction products modulate alveolar macrophage phagocytosis of
      Klebsiella pneumoniae.
AB  - The leukotrienes are potent lipid mediators of inflammation formed by the 5
      lipoxygenase-catalyzed oxidation of arachidonic acid. Although the effects of
      leukotrienes on neutrophil chemotaxis and activation have been established, their
      role in modulating innate host defense mechanisms is poorly understood. In a
      previous study (M. Bailie, T. Standiford, L. Laichalk, M. Coffey, R. Strieter,
      and M. Peters-Golden, J. Immunol. 157:5221-5224, 1996), we used 5-lipoxygenase
      knockout mice to establish a critical role for endogenous leukotrienes in
      pulmonary clearance and alveolar macrophage phagocytosis of Klebsiella
      pneumoniae. In the present study, we investigated the role of specific endogenous
      leukotrienes in phagocytosis of K. pneumoniae and explored the possibility that
      exogenous leukotrienes could restore phagocytosis in alveolar macrophages with
      endogenous leukotriene synthesis inhibition and enhance this process in
      leukotriene-competent cells. Rat alveolar macrophages produced leukotriene B4
      (LTB4), LTC4, and 5-hydoxyeicosatetraenoic acid (5-HETE) during the process of
      phagocytosis, and the inhibition of endogenous leukotriene synthesis with
      zileuton and MK-886 dramatically attenuated phagocytosis. We also observed a
      reduction in phagocytosis when we treated alveolar macrophages with antagonists
      to the plasma membrane receptors for either LTB4, cysteinyl-leukotrienes, or
      both. In leukotriene-competent cells, LTC4 augmented phagocytosis to the greatest
      extent, followed by 5-HETE and LTB4. These 5-lipoxygenase reaction products
      demonstrated similar relative abilities to reconstitute phagocytosis in zileuton
      treated rat alveolar macrophages and in alveolar macrophages from 5-lipoxygenase
      knockout mice. We conclude that endogenous synthesis of all major 5-lipoxygenase
      reaction products plays an essential role in phagocytosis. The restorative and
      pharmacologic effects of LTC4, LTB4, and 5-HETE may provide a basis for their
      exogenous administration as an adjunctive treatment for patients with gram
      negative bacterial pneumonia.

PMID- 9784516
TI  - Expression of the tpr protease gene of Porphyromonas gingivalis is regulated by
      peptide nutrients.
AB  - The Tpr protease of Porphyromonas gingivalis W83 is a membrane-associated enzyme
      capable of hydrolyzing chromogenic substrates for trypsin and bacterial
      collagenases. A previous study by us indicated that Tpr expression was increased
      under conditions of nutrient limitation. In the present study, we further
      characterized expression of the tpr gene using a tpr::lacZ reporter gene
      construct under a range of nutrient conditions. In P. gingivalis, transcription
      of tpr was initiated 215 bp upstream of the coding region and regulation of tpr
      expression was at the level of transcription. Deletion mutations in the tpr
      upstream region identified the promoter region immediately upstream of the
      transcription start site, determined by primer extension analysis. Three
      identical 17-bp direct repeats identified within the 5' end of tpr mRNA were
      involved in tpr regulation. In an Escherichia coli background, tpr transcription
      was initiated after an AT-rich region upstream of tpr but not at the P.
      gingivalis start site. Tpr expression in P. gingivalis was suppressed by the
      addition of peptide and protein nutrients to a peptide-limited growth medium but
      was only slightly affected by addition of free amino acids. Low-molecular-weight
      fractions of brain heart infusion rich in phenylalanine, proline, and alanine had
      the greatest inhibitory effects on expression of the tpr::lacZ construct.
      Addition of the dipeptide phenylalanyl-phenylalanine to the growth medium
      resulted in a 10-fold decrease in tpr expression. This suggests that specific
      phenylalanine-containing peptides are a major factor controlling Tpr expression.
      Neither hemin starvation, heat shock, nor pH change had significant effects on
      Tpr expression.

PMID- 9784517
TI  - Helicobacter hepaticus triggers colitis in specific-pathogen-free interleukin-10
      (IL-10)-deficient mice through an IL-12- and gamma interferon-dependent
      mechanism.
AB  - Mice rendered deficient in interleukin-10 (IL-10) by gene targeting (IL-10(-/-)
      mice) develop chronic enterocolitis resembling human inflammatory bowel disease
      (IBD) when maintained in conventional animal facilities. However, they display a
      minimal and delayed intestinal inflammatory response when reared under specific
      pathogen-free (SPF) conditions, suggesting the involvement of a microbial
      component in pathogenesis. We show here that experimental infection with a single
      bacterial agent, Helicobacter hepaticus, induces chronic colitis in SPF-reared IL
      10(-/-) mice and that the disease is accompanied by a type 1 cytokine response
      (gamma interferon [IFN-gamma], tumor necrosis factor alpha, and nitric oxide)
      detected by restimulation of spleen and mesenteric lymph node cells with a
      soluble H. hepaticus antigen (Ag) preparation. In contrast, wild-type (WT)
      animals infected with the same bacteria did not develop disease and produced IL
      10 as the dominant cytokine in response to Helicobacter Ag. Strong H. hepaticus
      reactive antibody responses as measured by Ag-specific total immunoglobulin G
      (IgG), IgG1, IgG2a, IgG2b, IgG3, and IgA were observed in both WT and IL-10(-/-)
      mice. In vivo neutralization of IFN-gamma or IL-12 resulted in a significant
      reduction of intestinal inflammation in H. hepaticus-infected IL-10(-/-) mice,
      suggesting an important role for these cytokines in the development of colitis in
      the model. Taken together, these microbial reconstitution experiments formally
      establish that a defined bacterial agent can serve as the immunological target in
      the development of large bowel inflammation in IL-10(-/-) mice and argue that in
      nonimmunocompromised hosts IL-10 stimulated in response to intestinal flora is
      important in preventing IBD.

PMID- 9784518
TI  - Altered immune responses in mice with concomitant Schistosoma mansoni and
      Plasmodium chabaudi infections.
AB  - Mixed parasitic infections are common in many parts of the world. However, little
      is known about how concurrent infections affect the immunity to and/or
      pathogenesis of each other. Protection and elimination of blood-stage Plasmodium
      chabaudi chabaudi AS in resistant mice are characterized by a sequential
      activation of CD4(+) Th1 and Th2 cells. The patent egg-laying stage of the murine
      model of Schistosoma mansoni is associated with a strong Th2 response to both
      Schistosoma and unrelated antigens. In this study, we investigated how infection
      of mice with S. mansoni would affect the immune response to and pathogenesis of a
      P. chabaudi infection. C57BL/6 mice infected with S. mansoni for 8 weeks were
      infected with blood-stage P. chabaudi. Malaria parasitemias were significantly
      higher in these mice than in mice infected with P. chabaudi only. In doubly
      infected mice, both spleen cell proliferative and Th2 responses to S. mansoni
      soluble egg antigen (SEA) or anti-CD3 were suppressed up to 1 month after the
      malaria infection. Findings for SEA-specific immunoglobulin M (IgM) and IgG serum
      antibody levels were similar. No significant effects were seen on P. chabaudi
      induced gamma interferon responses. However, tumor necrosis factor alpha (TNF
      alpha) production was significantly lower in double-infected mice. Thus, a defect
      in TNF-alpha production might contribute to the increased malaria parasitemias
      seen in S. mansoni-P. chabaudi-infected mice. Taken together, our data show that
      schistosoma and malaria infections profoundly affect each other, findings which
      might have implications for the development of vaccines.

PMID- 9784520
TI  - Staphylococcus aureus serotype 5 capsular polysaccharide is antiphagocytic and
      enhances bacterial virulence in a murine bacteremia model.
AB  - Controversy persists over the role that the capsular polysaccharide plays in the
      pathogenesis of Staphylococcus aureus infections. To address this issue, we
      compared the mouse virulence of S. aureus Reynolds and capsule-defective mutant
      strains cultivated under conditions of high or low capsule expression. Strain
      Reynolds cells cultivated on Columbia salt agar plates expressed approximately
      100-fold more type 5 capsular polysaccharide than did cells cultivated in
      Columbia salt broth. The relative virulence of strain Reynolds and its capsule
      defective mutants after growth on either solid or liquid medium was examined in
      mice challenged intraperitoneally or intravenously. The results indicated that
      agar-grown Reynolds cells were cleared from the bloodstream of mice less readily
      than broth-grown Reynolds cells. When the parental and mutant strains were
      cultivated on solid medium, strain Reynolds sustained a higher level of
      bacteremia than did the capsular mutants. We performed in vitro opsonophagocytic
      killing assays to determine whether staphylococcal virulence for mice correlated
      with resistance to phagocytosis. S. aureus Reynolds cultivated on solid medium
      was susceptible to phagocytic killing only in the presence of specific capsular
      antibodies and complement. Strain Reynolds grown in broth showed opsonic
      requirements for phagocytic killing that were similar to those of the capsular
      mutants (grown in broth or on agar); i.e., the bacteria were opsonized for
      phagocytosis by nonimmune serum with complement activity. These studies indicate
      that optimal expression of capsule enhances bacterial virulence in the mouse
      model of bacteremia, probably by rendering the organisms resistant to
      opsonophagocytic killing by leukocytes.

PMID- 9784519
TI  - Immunological characterization of Asp f 2, a major allergen from Aspergillus
      fumigatus associated with allergic bronchopulmonary aspergillosis.
AB  - The 37-kDa recombinant protein Asp f 2, encoding an allergen of Aspergillus
      fumigatus, was expressed in a prokaryotic expression system and immunologically
      evaluated for its functional and structural properties. The open reading frame
      for a 310-amino-acid-long protein was shown to encode a signal peptide of 31
      amino acids. A native 37-kDa culture filtrate protein and a 55-kDa mycelial
      glycoprotein (gp55) exhibited complete N-terminal sequence homology to Asp f 2. A
      GenBank search for homologous proteins revealed 60 and 44% sequence homologies to
      the cytosolic protein ASPND1 from Aspergillus nidulans and fibrinogen binding
      protein from Candida albicans, respectively. The glycosylation sites and cysteine
      molecules are conserved in all the three proteins. The extracellular matrix
      protein laminin showed a dose-dependent interaction with Asp f 2. This protein,
      expressed as a major cell-associated protein within 24 h of in vitro fungal
      culture, comprises 20 to 40% of total fungal protein. Furthermore, both native
      and recombinant Asp f 2 exhibited specific immunoglobulin (IgE) binding with
      allergic bronchopulmonary aspergillosis (ABPA) and cystic fibrosis-ABPA patients,
      whereas A. fumigatus-sensitized allergic asthma and normal control subjects
      failed to show IgE binding with Asp f 2. These results indicate that Asp f 2 is a
      major allergen of A. fumigatus exhibiting IgE antibody binding with sera from
      patients with ABPA. The antigen should be explored further for its potential role
      in the differential diagnosis of A. fumigatus-associated allergic diseases.

PMID- 9784521
TI  - In situ detection of apoptosis at sites of chronic bacterially induced
      inflammation in human gingiva.
AB  - Apoptosis is a key phenomenon in the regulation of the life span of terminally
      differentiated leukocytes. Human gingiva represents an established model to study
      immune responses to bacterial infection. In this investigation, we used the TUNEL
      (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling)
      technique to evaluate presence and topographic location of apoptosis-associated
      DNA damage in human gingival biopsies along with the expression of the p53 and
      Bcl-2 apoptosis-regulating proteins. Qualitative data analysis showed high
      densities of cells expressing DNA damage and p53 both within the epithelial
      attachment to the tooth and in the perivascular infiltrate (infiltrated
      connective tissue [ICT]) immediately underlying the site of chronic bacterial
      aggression. Topographic consistency between DNA damage- and p53-positive cells
      was consistently observed. Quantitative analysis of the ICT showed mean densities
      of DNA damage- and p53-positive cells of 345 +/- 278 and 403 +/- 182 cells/mm2,
      respectively. Numerical consistency was confirmed by multivariate regression
      analysis: densities of DNA damage-positive cells were significantly predicted by
      densities of p53-positive cells (P = 0. 001, r2 = 0.84). In the ICT, cells
      displaying biotinylated DNA nicks were 3.8% +/- 2.7% of total cellularity, while
      p53- and Bcl-2-positive cells represented 4.4% +/- 1.7% and 15.4% +/- 6.7% of
      total cells, respectively. It is suggested that p53 expression associated with
      DNA damage is a prevalent phenomenon in chronically inflamed human gingiva, and
      that apoptosis may be a relevant process for the maintenance of local immune
      homeostasis at sites of chronic bacterial challenge in vivo.

PMID- 9784522
TI  - Lipoprotein release by bacteria: potential factor in bacterial pathogenesis.
AB  - Lipoprotein (LP) is a major component of the outer membrane of bacteria in the
      family Enterobacteriaceae. LP induces proinflammatory cytokine production in
      macrophages and lethal shock in LPS-responsive and -nonresponsive mice. In this
      study, the release of LP from growing bacteria was investigated by immuno-dot
      blot analysis. An immuno-dot blot assay that could detect LP at levels as low as
      100 ng/ml was developed. By using this assay, significant levels of LP were
      detected in culture supernatants of growing Escherichia coli cells. During mid
      logarithmic growth, approximately 1 to 1.5 microgram of LP per ml was detected in
      culture supernatants from E. coli. In contrast, these culture supernatants
      contained 5 to 6 microgram/ml of lipopolysaccharide (LPS). LP release was not
      unique to E. coli. Salmonella typhimurium, Yersinia enterocolitica, and two
      pathogenic E. coli strains also released LP during in vitro growth. Treatment of
      bacteria with the antibiotic ceftazidime significantly enhanced LP release.
      Culture supernatants from 5-h cultures of E. coli were shown to induce in vitro
      production of interleukin-6 (IL-6) by macrophages obtained from LPS-nonresponsive
      C3H/HeJ mice. In contrast, culture supernatants from an E. coli LP-deletion
      mutant were significantly less efficient at inducing IL-6 production in C3H/HeJ
      macrophages. These results suggest, for the first time, that LP is released from
      growing bacteria and that this released LP may play an important role in the
      induction of cytokine production and pathologic changes associated with gram
      negative bacterial infections.

PMID- 9784523
TI  - The major outer membrane protein of Chlamydia psittaci functions as a porin-like
      ion channel.
AB  - The major outer membrane protein (MOMP) of Chlamydia species shares several
      biochemical properties with classical porin proteins. Secondary structure
      analysis by circular dichroism now reveals that MOMP purified from Chlamydia
      psittaci has a predominantly beta-sheet content (62%), which is also typical of
      bacterial porins. Can MOMP form functional ion channels? To directly test the
      "porin channel" hypothesis at the molecular level, the MOMP was reconstituted
      into planar lipid bilayers, where it gave rise to multibarreled channels,
      probably trimers, which were modified by an anti-MOMP monoclonal antibody. These
      observations are consistent with the well-characterized homo-oligomeric nature of
      MOMP previously revealed by biochemical analysis and with the triple-barreled
      behavior of other porins. MOMP channels were weakly anion selective (PCl/PK
      approximately 2) and permeable to ATP. They may therefore be a route by which
      Chlamydia can take advantage of host nucleoside triphosphates and explain why
      some anti-MOMP antibodies neutralize infection. These findings have broad
      implications on the search for an effective chlamydial vaccine to control the
      significant human and animal diseases caused by these organisms.

PMID- 9784524
TI  - Activation of natural killer cells in arthritis-susceptible but not arthritis
      resistant mouse strains following Borrelia burgdorferi infection.
AB  - Infection of susceptible mouse strains with Borrelia burgdorferi, the agent of
      Lyme disease, results in the development of arthritis. Components of the innate
      immune system may be important mediators of this pathology. To investigate the
      potential role of NK cells in development of experimental Lyme arthritis, we
      examined their activation in vivo in both resistant and susceptible mouse
      strains. Following inoculation of B. burgdorferi into the footpad, lymph node NK
      cells from susceptible C3H/HeJ (C3H) mice produced more gamma interferon than NK
      cells from resistant DBA/2J mice. Lymph node cells from susceptible C3H and AKR
      mice also had increased ability to lyse YAC-1 target cells 2 days following
      infection. Antibody depletion of NK cells from susceptible mice, however, did not
      alter the development of arthritis following B. burgdorferi challenge. In
      addition, NK cell depletion had little effect on spirochete burden. Thus, there
      is a marked activation of NK cells in susceptible mouse strains following
      infection. Although NK cells are not absolutely required for arthritis, events
      occurring prior to NK cell activation might be important in mediating pathology
      in experimental Lyme disease.

PMID- 9784525
TI  - Neisseria gonorrhoeae heme biosynthetic mutants utilize heme and hemoglobin as a
      heme source but fail to grow within epithelial cells.
AB  - Many bacterial pathogens, including pathogenic neisseriae, can use heme as an
      iron source for growth. To study heme utilization by Neisseria gonorrhoeae, two
      heme biosynthetic mutants were constructed, one with a mutation in hemH (the gene
      encoding ferrochelatase) and one with a mutation in hemA (the gene encoding gamma
      glutamyl tRNA reductase). The hemH mutant failed to grow without an exogenous
      supply of heme or hemoglobin, whereas the hemA mutant failed to grow unless heme,
      hemoglobin, or heme precursors were present. Growth of the mutants with
      hemoglobin required expression of the hemoglobin receptor (HpuAB) and was TonB
      dependent. However, growth with heme required neither HpuAB nor TonB. An fbpA
      mutant grew normally when either heme or hemoglobin was present in the medium.
      The heme biosynthetic mutants showed reduced intracellular survival, compared to
      the parent strain, within A-431 endocervical epithelial cell cultures. These
      studies demonstrate that in addition to synthesizing their own heme, N.
      gonorrhoeae strains are able to internalize and utilize exogenous heme
      independently of FbpA but appear unable to obtain heme from within epithelial
      cells for growth.

PMID- 9784526
TI  - Resident enteric bacteria are necessary for development of spontaneous colitis
      and immune system activation in interleukin-10-deficient mice.
AB  - Mice with targeted deletion of the gene for interleukin-10 (IL-10) spontaneously
      develop enterocolitis when maintained in conventional conditions but develop only
      colitis when kept in specific-pathogen-free (SPF) environments. This study tested
      the hypothesis that enteric bacteria are necessary for the development of
      spontaneous colitis and immune system activation in IL-10-deficient mice. IL-10
      deficient mice were maintained in either SPF conditions or germfree conditions or
      were populated with bacteria known to cause colitis in other rodent models. IL-10
      deficient mice kept in SPF conditions developed colitis in all segments of the
      colon (cecum and proximal and distal colon). These mice exhibited immune system
      activation as evidenced by increased expression of CD44 on CD4(+) T cells;
      increased mesenteric lymph node cell numbers; and increased production of
      immunoglobulin A (IgA), IgG1, and IL-12 p40 from colon fragment cultures. Mice
      populated with bacterial strains, including Bacteroides vulgatus, known to induce
      colitis in other rodent models had minimal colitis. Germfree IL-10-deficient mice
      had no evidence of colitis or immune system activation. We conclude therefore
      that resident enteric bacteria are necessary for the development of spontaneous
      colitis and immune system activation in IL-10-deficient mice.

PMID- 9784527
TI  - Regulation of protease expression in Porphyromonas gingivalis.
AB  - Although the strong protease activity of Porphyromonas gingivalis appears to be
      an important virulence property of these organisms, little information is
      currently available regarding the regulation of expression of the multiple
      protease genes. Utilizing the lacZ reporter gene strategy, the environmental
      factors which regulate the expression of the Arg-gingipain gene rgpA and the prtT
      protease gene were investigated. These two genes are reciprocally regulated since
      factors which retarded growth (iron depletion and nutrient limitation) appeared
      to upregulate rgpA expression while down-regulating prtT expression. However,
      inactivation of the major rgpA gene resulted in increased transcription of the
      prtT and tpr protease genes while decreasing expression of the Lys-gingipain kgp
      gene as detected by Northern blot analysis. By contrast, inactivation of the prtT
      gene did not significantly affect kgp expression but moderately decreased rgpA
      mRNA levels. These results indicate that the protease genes of P. gingivalis are
      not coordinately regulated and suggest that some of these enzymes play specific
      roles in the physiology and/or virulence of these organisms.

PMID- 9784528
TI  - Staphylococcus aureus Agr and Sar global regulators influence internalization and
      induction of apoptosis.
AB  - Staphylococcus aureus was recently shown to be internalized by and to induce
      apoptosis in a bovine mammary epithelial cell line, suggesting that these
      processes could be involved in staphylococcal pathogenesis or persistence. To
      examine the role of virulence factor regulators during internalization, mutant
      agr and sar strains of S. aureus were analyzed for their abilities to enter and
      induce apoptosis in epithelial cells. Like a previously characterized bovine
      mastitis isolate, the standard laboratory strain, RN6390 (wild type), entered the
      epithelial cells and subsequently induced apoptosis. In contrast, the mutant
      strains RN6911 (agr), ALC136 (sar), and ALC135 (agr sar) were internalized by the
      cultured cells at levels reproducibly greater than that for RN6390 but failed to
      induce apoptosis. The internalization of S. aureus was affected by growth phase,
      suggesting a role for agr-regulated surface proteins in this process.
      Furthermore, the ability to induce apoptosis required metabolically active
      intracellular bacteria. These data indicate that the ability of S. aureus to
      enter mammalian cells and induce apoptosis is dependent on factors regulated by
      Agr and Sar. Since transcriptional control by these global regulators is mediated
      by quorum-sensing and environmental factors, staphylococci may have the potential
      to induce several alternative effects on cells from an intracellular environment.
      A model for the function of the agr locus in the context of internalization,
      intracellular persistence, and dissemination is proposed.

PMID- 9784529
TI  - Bordetella avium virulence measured in vivo and in vitro.
AB  - Bordetella avium causes an upper-respiratory-tract disease called bordetellosis
      in birds. Bordetellosis shares many of the clinical and histopathological
      features of disease caused in mammals by Bordetella pertussis and Bordetella
      bronchiseptica. In this study we determined several parameters of infection in
      the domestic turkey, Meleagris galapavo, and compared these in vivo findings with
      an in vitro measure of adherence using turkey tracheal rings. In the in vivo
      experiments, we determined the effects of age, group size, infection duration,
      and interindividual spread of B. avium. Also, the effect of host genetic
      background on susceptibility was tested in the five major commercial turkey lines
      by infecting each with the parental B. avium strain and three B. avium insertion
      mutants. The mutant strains lacked either motility, the ability to agglutinate
      guinea pig erythrocytes, or the ability to produce dermonecrotic toxin. The
      susceptibilities of 1-day-old and 1-week-old turkeys to B. avium were the same,
      and challenge group size (5, 8, or 10 birds) had no effect upon the 50%
      infectious dose. Two weeks between inoculation and tracheal culture was optimal,
      since an avirulent mutant (unable to produce dermonecrotic toxin) persisted for a
      shorter time. Communicability of the B. avium parental strain between confined
      birds was modest, but a nonmotile mutant was less able to spread between birds.
      There were no host-associated differences in susceptibility to the parental
      strain and the three B. avium mutant strains just mentioned: in all turkey lines
      tested, the dermonecrotic toxin- and hemagglutination-negative mutants were
      avirulent whereas the nonmotile mutants showed no loss of virulence.
      Interestingly, the ability of a strain to cause disease in vivo correlated
      completely with its ability to adhere to ciliated tracheal cells in vitro.

PMID- 9784530
TI  - Disruption of an internal membrane-spanning region in Shiga toxin 1 reduces
      cytotoxicity.
AB  - Shiga toxin type 1 (Stx1) belongs to the Shiga family of bipartite AB toxins that
      inactivate eukaryotic 60S ribosomes. The A subunit of Stxs are N-glycosidases
      that share structural and functional features in their catalytic center and in an
      internal hydrophobic region that shows strong transmembrane propensity. Both
      features are conserved in ricin and other ribosomal inactivating proteins. During
      eukaryotic cell intoxication, holotoxin likely moves retrograde from the Golgi
      apparatus to the endoplasmic reticulum. The hydrophobic region, spanning residues
      I224 through N241 in the Stx1 A subunit (Stx1A), was hypothesized to participate
      in toxin translocation across internal target cell membranes. The TMpred computer
      program was used to design a series of site-specific mutations in this
      hydrophobic region that disrupt transmembrane propensity to various degrees.
      Mutations were synthesized by PCR overlap extension and confirmed by DNA
      sequencing. Mutants StxAF226Y, A231D, G234E, and A231D-G234E and wild-type Stx1A
      were expressed in Escherichia coli SY327 and purified by dye-ligand affinity
      chromatography. All of the mutant toxins were similar to wild-type Stx1A in
      enzymatic activity, as determined by inhibition of cell-free protein synthesis,
      and in susceptibility to trypsin digestion. Purified mutant or wild-type Stx1A
      combined with Stx1B subunits in vitro to form a holotoxin, as determined by
      native polyacrylamide gel electrophoresis immunoblotting. StxA mutant A231D
      G234E, predicted to abolish transmembrane propensity, was 225-fold less cytotoxic
      to cultured Vero cells than were the wild-type toxin and the other mutant toxins
      which retained some transmembrane potential. Furthermore, compared to wild-type
      Stx1A, A231D-G234E Stx1A was less able to interact with synthetic lipid vesicles,
      as determined by analysis of tryptophan fluorescence for each toxin in the
      presence of increasing concentrations of lipid membrane vesicles. These results
      provide evidence that this conserved internal hydrophobic motif contributes to
      Stx1 translocation in eukaryotic cells.

PMID- 9784532
TI  - Acquired resistance but not innate resistance to Mycobacterium bovis bacillus
      Calmette-Guerin is compromised by interleukin-12 ablation.
AB  - Interleukin-12 (IL-12) is one of the first cytokines produced by macrophages, key
      mediators of innate resistance, during the host's immune response to infections.
      Therefore, in this study we propose that IL-12 has an important role in the early
      phase of the immune response to Mycobacterium bovis BCG. IL-12 has been shown to
      enhance the maturation of protective Th1 cells and gamma interferon (IFN-gamma)
      production during mycobacterial infection. Therefore, it may play a crucial role
      during the immune phase of infection as well. To examine the role of IL-12 in
      both the innate and the immune phase of infection, we compared BCG-resistant
      mice, B10.A (Bcgr), to the susceptible congenic strain B10.A (Bcgs) following
      administration of a blocking monoclonal antibody to IL-12 (10F6). Anti-IL-12
      treated susceptible animals exhibited a two- to threefold increase in spleen CFU
      by day 21. In contrast, anti-IL-12 treatment had little or no effect on the
      response of the genetically resistant animals to infection. The B10.A (Bcgr) but
      not the B10.A (Bcgs) mice had an increase in IFN-gamma mRNA relative to baseline
      levels as early as day 1 of infection irrespective of anti-IL-12 treatment. By
      day 14, B10.A (Bcgr) mice showed a decrease in IFN-gamma mRNA while the B10.A
      (Bcgs) mice showed a significant increase in IFN-gamma mRNA levels. Thus, during
      BCG infection, the B10.A (Bcgr) mice mount an early IFN-gamma response against
      BCG whereas the B10.A (Bcgs) mice have a delayed IFN-gamma response correlating
      with their genetic permissiveness expressed as an increased mycobacterial load by
      day 21. Overall, our data demonstrate that the inherent resistance of B10.A
      (Bcgr) mice to mycobacteria does not depend on optimal levels of IL-12 to
      maintain effective control of the bacteria, whereas IL-12 is important for the
      susceptible animals' response to BCG during the peak of infection.

PMID- 9784531
TI  - Interaction of Listeria monocytogenes with human brain microvascular endothelial
      cells: InlB-dependent invasion, long-term intracellular growth, and spread from
      macrophages to endothelial cells.
AB  - Invasion of endothelial tissues may be crucial in a Listeria monocytogenes
      infection leading to meningitis and/or encephalitis. Internalization of L.
      monocytogenes into endothelial cells has been previously demonstrated by using
      human umbilical vein endothelial cells as a model system. However, during the
      crossing of the blood-brain barrier, L. monocytogenes most likely encounters
      brain microvascular endothelial cells which are strikingly different from
      macrovascular or umbilical vein endothelial cells. In the present study human
      brain microvascular endothelial cells (HBMEC) were used to study the interaction
      of L. monocytogenes with endothelial cells, which closely resemble native
      microvascular endothelial cells of the brain. We show that L. monocytogenes
      invades HBMEC in an InlB-dependent and wortmannin-insensitive manner. Once within
      the HBMEC, L. monocytogenes replicates efficiently over a period of at least 18
      h, moves intracellularly by inducing actin tail formation, and spreads from cell
      to cell. Using a green fluorescent protein-expressing L. monocytogenes strain, we
      present direct evidence that HBMEC are highly resistant to damage by
      intracellularly growing L. monocytogenes. Infection of HBMEC with L.
      monocytogenes results in foci of heavily infected, but largely undamaged
      endothelial cells. Heterologous plaque assays with L. monocytogenes-infected
      P388D1 macrophages as vectors demonstrate efficient spreading of L. monocytogenes
      into HBMEC, fibroblasts, hepatocytes, and epithelial cells, and this phenomenon
      is independent of the inlC gene product.

PMID- 9784533
TI  - Molecular analysis of sequence heterogeneity among genes encoding decorin binding
      proteins A and B of Borrelia burgdorferi sensu lato.
AB  - Immunization of mice with Borrelia burgdorferi decorin binding protein A (DbpA),
      one of two gene products of the dbpBA locus, has been shown recently to confer
      protection against challenge. Hyperimmune DbpA antiserum killed a large number of
      B. burgdorferi sensu lato isolates of diverse phylogeny and origin, suggesting
      conservation of the protective epitope(s). In order to evaluate the heterogeneity
      of DbpA and DbpB and to facilitate defining the conserved epitope(s) of these
      antigens, the sequences of the dbpA genes from 29 B. burgdorferi sensu lato
      isolates and of the dbpB genes from 15 B. burgdorferi sensu lato isolates were
      determined. The predicted DbpA sequences were fairly heterogeneous among the
      isolates (58.3 to 100% similarity), but DbpA sequences with the highest
      similarity tended to group into species previously defined by well-characterized
      chromosomal markers. In contrast, the predicted DbpB sequences were highly
      conserved (96.3 to 100% similarity). Substantial diversity in DbpA sequence was
      seen among isolates previously shown to be killed by antiserum against a single
      DbpA, suggesting that one or more conserved protective epitopes are composed of
      noncontiguous amino acids. The observation of individual dbpA alleles with
      sequence elements characteristic of more than one B. burgdorferi sensu lato
      species was consistent with a role for genetic recombination in the generation of
      dbpA diversity.

PMID- 9784535
TI  - Inhibition of Salmonella typhimurium invasion by host cell expression of secreted
      bacterial invasion proteins.
AB  - Pathogenic Salmonella species initiate infection of a host by inducing their own
      uptake into intestinal epithelial cells. An invasive phenotype is conferred to
      this pathogen by a number of proteins that are components of a type III secretion
      system. During the invasion process, the bacteria utilize this secretion system
      to release proteins that enter the host cell and apparently interact with unknown
      host cell components that induce alterations in the actin cytoskeleton. To
      investigate the role of secreted proteins as direct modulators of invasion, we
      have evaluated the ability of Salmonella typhimurium to enter mammalian cells
      that express portions of the Salmonella invasion proteins SipB and SipC. Plasma
      membrane localization of SipB and SipC was achieved by fusing carboxyl- and amino
      terminal portions of each invasion protein to the intracellular carboxyl-terminal
      tail of a membrane-bound eukaryotic receptor. Expression of receptor chimeras
      possessing the carboxyl terminus of SipB or the amino terminus of SipC blocked
      Salmonella invasion, whereas expression of their chimeric counterparts had no
      effect on invasion. The effect on invasion was specific for Salmonella since the
      perturbation of uptake was not extended to other invasive bacterial species.
      These results suggest that Salmonella invasion can be competitively inhibited by
      preventing the intracellular effects of SipB or SipC. In addition, these
      experiments provide a model for examining interactions between bacterial invasion
      proteins and their host cell targets.

PMID- 9784534
TI  - Role of liver NK cells and peritoneal macrophages in gamma interferon and
      interleukin-10 production in experimental bacterial peritonitis in mice.
AB  - Gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and
      interleukin-10 (IL-10) production by liver, spleen, lung, peripheral blood
      mononuclear cells (MNC), and peritoneal exudate cells (PEC) in experimental
      bacterial peritonitis was examined by cecum ligation and puncture (CLP) (with an
      18-gauge needle) of BALB/c mice. MNC of organs were cultured for 18 h, and
      cytokine levels in supernatants were examined. Cytokines contained in peritoneal
      lavage fluid were regarded as those produced by PEC. Only liver MNC and PEC
      produced substantial amounts of IFN-gamma, and PEC were the main source of IL-10,
      especially 12 h after CLP. As reflected by the cytokine production by liver MNC
      and PEC, serum IFN-gamma and IL-10 levels were elevated after CLP. C57BL/6 (B6)
      mice and BALB/c nude mice showed a similar pattern of cytokine production. TNF
      alpha levels in culture supernatants, peritoneal lavage fluid, and sera were not
      significantly elevated compared to those of sham-operated mice. In vivo depletion
      of NK cells of B6 mice with anti-asialo GM1 or anti-NK1.1 antibody greatly
      decreased IFN-gamma levels in liver MNC culture supernatants and sera, suggesting
      that liver NK cells are IFN-gamma producers. On the other hand, plastic-adherent
      PEC macrophages are the major IL-10 producers. Mice subjected to a cecum ligation
      and cut procedure (which have a more severe peritonitis) showed much higher IFN
      gamma and IL-10 levels than those subjected to CLP, while mice subjected to CLP
      with a smaller (22-gauge) needle showed low levels of these cytokines. These
      findings show that liver NK cells and PEC macrophages are important for the
      production of proinflammatory and anti-inflammatory cytokines in bacterial
      peritonitis.

PMID- 9784536
TI  - Altered expression of selectable marker URA3 in gene-disrupted Candida albicans
      strains complicates interpretation of virulence studies.
AB  - The ura-blaster technique for the disruption of Candida albicans genes has been
      employed in a number of studies to identify possible genes encoding virulence
      factors of this fungal pathogen. In this study, the URA3-encoded orotidine 5'
      monophosphate (OMP) decarboxylase enzyme activities of C. albicans strains with
      ura-blaster-mediated genetic disruptions were measured. All strains harboring
      genetic lesions via the ura-blaster construct showed reduced OMP decarboxylase
      activities compared to that of the wild type when assayed. The activity levels in
      different gene disruptions varied, suggesting a positional effect on the level of
      gene expression. Because the URA3 gene of C. albicans has previously been
      identified as a virulence factor for this microorganism, our results suggest that
      decreased virulence observed in strains constructed with the ura-blaster cassette
      cannot accurately be attributed, in all cases, to the targeted genetic
      disruption. Although revised methods for validating a URA3-disrupted gene as a
      target for antifungal drug development could be devised, it is clearly desirable
      to replace URA3 with a different selectable marker that does not influence
      virulence.

PMID- 9784537
TI  - Subcellular localization and cytotoxic activity of the GroEL-like protein
      isolated from Actinobacillus actinomycetemcomitans.
AB  - The subcellular locations, ultrastructure, and cytotoxic activity of the GroEL
      like protein from Actinobacillus actinomycetemcomitans were investigated. Two
      dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)
      clearly indicated that synthesis of the GroEL-like protein is substantially
      increased after a thermal shock. Analysis of the purified native GroEL-like
      protein by transmission electron microscopy revealed the typical 14-mer
      cylindrical molecule, which had a diameter of about 12 nm. A.
      actinomycetemcomitans cells grown at 35 degreesC and heat shocked at 43 degreesC
      were fractionated, and fractions were separated by SDS-PAGE and analyzed by
      Western immunoblotting using antibodies to GroEL- and DnaK-like proteins. The
      GroEL-like protein was found in both the soluble and membrane fractions, whereas
      the DnaK-like protein was mostly found in the cytoplasm. An increase in specific
      proteins, including the GroEL- and DnaK-like proteins, was found in heat-shocked
      cells. The subcellular localization of the GroEL-like protein was examined by
      immunoelectron microscopy of whole cells. More GroEL-like protein was detected in
      stressed cells than in unstressed cells, and most of it was found not directly
      associated with outer membranes but rather in extracellular material. The native
      GroEL-like protein was assessed for cytotoxic activities. The GroEL-like protein
      increased the proliferation of periodontal ligament epithelial cells at
      concentrations between 0.4 and 1.0 microgram/ml. The number of cells in the
      culture decreased significantly at higher concentrations. A cell viability assay
      using HaCaT epithelial cells indicated that the GroEL-like protein was strongly
      toxic for the cells. These studies suggest the extracellular nature of the GroEL
      like protein and its putative role in disease initiation.

PMID- 9784538
TI  - 1,25-Dihydroxyvitamin D3 induces nitric oxide synthase and suppresses growth of
      Mycobacterium tuberculosis in a human macrophage-like cell line.
AB  - Inducible synthesis of nitric oxide (NO) by macrophages is an important mechanism
      of the host defense against intracellular infection in mice, but the evidence for
      significant levels of inducible NO production by human macrophages is
      controversial. Here we report that the human promyelocytic cell line HL-60, when
      differentiated to a macrophage-like phenotype, acquires the ability to produce
      substantial amounts of NO on stimulation with LPS or 1, 25-dihydroxyvitamin D3
      (1,25-D3) in the absence of activating factors such as gamma interferon.
      Expression of the inducible nitric oxide synthase (NOS2) was confirmed by
      sequencing of the reverse transcription-PCR product from stimulated HL-60 cells.
      Kinetic studies after lipopolysaccharide stimulation show that NOS2 mRNA levels
      rise within 3 to 6 h, that conversion of [14C]arginine to [14C]citrulline is
      maximal at 5 to 6 days, and that levels of reactive nitrogen intermediates
      stabilize at around 20 microM at 7 to 8 days. We find that 1,25-D3 acts to
      suppress the growth of Mycobacterium tuberculosis in these cells and that this
      effect is inhibited by NG-monomethyl-L-arginine, suggesting that vitamin D
      induced NO production may play a role in the host defense against human
      tuberculosis.

PMID- 9784539
TI  - The p29 and p35 immunodominant antigens of Neospora caninum tachyzoites are
      homologous to the family of surface antigens of Toxoplasma gondii.
AB  - Neospora caninum is an apicomplexan parasite that is closely related to
      Toxoplasma gondii and has been found to be associated with neurological disorders
      in dogs and congenital infections and abortions in cattle. We have identified two
      surface proteins of 29 and 35 kDa (designated Ncp29 and Ncp35, respectively) from
      N. caninum tachyzoites that are the predominant antigens recognized by antisera
      from Neospora-infected animals. Monoclonal antibodies against Ncp29 and Ncp35
      were used to analyze several independent and diverse N. caninum isolates; both
      antigens were recognized in all isolates, suggesting that they are well
      conserved. Localization studies and surface labeling with biotin demonstrated
      that Ncp29 and Ncp35 are membrane associated and displayed on the surface of the
      parasite. After treatment with phosphatidylinositol-specific phospholipase C,
      parasite lysates were analyzed with antibodies against the cross-reacting
      determinant of glycosylphosphatidylinositol anchors. Approximately six glycolipid
      anchored surface proteins were identified, with the two most prominent
      corresponding to Ncp29 and Ncp35. Sequence comparisons of Ncp29 and Ncp35 with
      GenBank indicated that they are most similar to the T. gondii surface antigen 1
      (SAG1) and surface antigen 1-related sequence 2 (SRS2), respectively.
      Consequently, Ncp29 has been designated NcSAG1 and Ncp35 has been designated
      NcSRS2. Both NcSAG1 and NcSRS2 contain a tandemly duplicated motif and 12
      absolutely conserved cysteines which are also found in all of the SAG and SRS
      proteins of T. gondii. Maintenance of these motifs and the 12 cysteine residues
      suggests that these surface antigens share a similar secondary and tertiary
      structure that is presumably important for a conserved function that these
      antigens serve during infection.

PMID- 9784540
TI  - Pathways for potentiation of immunogenicity during adjuvant-assisted
      immunizations with Plasmodium falciparum major merozoite surface protein 1.
AB  - Vaccine adjuvants exert critical and unique influences on the quality of immune
      responses induced during active immunizations. We investigated the mechanisms of
      action of immunological adjuvants in terms of their requirements for cytokine
      mediated pathways for adjuvanticity. Antibody responses potentiated by several
      adjuvants to a Plasmodium falciparum MSP1-19 (C-terminal 19-kDa processing
      fragment of MSP1) vaccine were studied in gamma interferon (IFN-gamma) or
      interleukin (IL-4) knockout mice. The levels of anti-MSP1-19 antibodies and the
      induction of Th1- and Th2-type antibodies were analyzed. Results revealed a
      spectrum of requirements for cytokine-mediated pathways in the potentiation of
      immunogenicity, and such requirements were influenced by interactions among
      individual components of the adjuvant formulations. One adjuvant strictly
      depended on IFN-gamma to induce appreciable levels of anti-MSP1-19 antibodies,
      while some formulations required IFN-gamma only for the induction of Th1-type
      antibodies. Other formulations induced exclusively Th2-type antibodies and were
      not affected by IFN-gamma knockout. There were three patterns of requirements for
      IL-4 by various adjuvants in the induction of Th2-type anti-MSP1-19 antibodies.
      Moreover, the induction of Th1-type anti-MSP1-19 antibodies by adjuvants showed
      two distinct patterns of regulation by IL-4. The utilization of an IL-4 regulated
      pathway(s) for the induction of Th2-type antibodies by the same adjuvant differed
      between mouse strains, suggesting that animal species variability in responses to
      vaccine adjuvants may be due, at least in part, to differences in the utilization
      of immune system pathways by an adjuvant among animal hosts.

PMID- 9784541
TI  - Invasion of aortic and heart endothelial cells by Porphyromonas gingivalis.
AB  - Invasion of host cells is believed to be an important strategy utilized by a
      number of pathogens, which affords them protection from the host immune system.
      The connective tissues of the periodontium are extremely well vascularized, which
      allows invading microorganisms, such as the periodontal pathogen Porphyromonas
      gingivalis, to readily enter the bloodstream. However, the ability of P.
      gingivalis to actively invade endothelial cells has not been previously examined.
      In this study, we demonstrate that P. gingivalis can invade bovine and human
      endothelial cells as assessed by an antibiotic protection assay and by
      transmission and scanning electron microscopy. P. gingivalis A7436 was
      demonstrated to adhere to and to invade fetal bovine heart endothelial cells
      (FBHEC), bovine aortic endothelial cells (BAEC), and human umbilical vein
      endothelial cells (HUVEC). Invasion efficiencies of 0.1, 0.2, and 0. 3% were
      obtained with BAEC, HUVEC, and FBHEC, respectively. Invasion of FBHEC and BAEC by
      P. gingivalis A7436 assessed by electron microscopy revealed the formation of
      microvillus-like extensions around adherent bacteria followed by the engulfment
      of the pathogen within vacuoles. Invasion of BAEC by P. gingivalis A7436 was
      inhibited by cytochalasin D, nocodazole, staurosporine, protease inhibitors, and
      sodium azide, indicating that cytoskeletal rearrangements, protein
      phosphorylation, energy metabolism, and P. gingivalis proteases are essential for
      invasion. In contrast, addition of rifampin, nalidixic acid, and chloramphenicol
      had little effect on invasion, indicating that bacterial RNA, DNA, and de novo
      protein synthesis are not required for P. gingivalis invasion of endothelial
      cells. Likewise de novo protein synthesis by endothelial cells was not required
      for invasion by P. gingivalis. P. gingivalis 381 was demonstrated to adhere to
      and to invade BAEC (0.11 and 0.1% efficiency, respectively). However, adherence
      and invasion of the corresponding fimA mutant DPG3, which lacks the major
      fimbriae, was not detected. These results indicate that P. gingivalis can
      actively invade endothelial cells and that fimbriae are required for this
      process. P. gingivalis invasion of endothelial cells may represent another
      strategy utilized by this pathogen to thwart the host immune response.

PMID- 9784542
TI  - Diversity of antigen recognition by serum antibodies in experimental bovine
      tuberculosis.
AB  - Tuberculosis in cattle remains a major zoonotic and economic problem in many
      countries. The standard diagnostic assay for bovine tuberculosis, the intradermal
      tuberculin test, has low accuracy. Therefore, alternative immunodiagnostic
      methods, such as serological assays, are needed for detection of infected
      animals. Development of an accurate serodiagnostic test requires a detailed
      understanding of the humoral immune responses during bovine tuberculosis and, in
      particular, identification of the key antigens of Mycobacterium bovis involved in
      antibody production. In this study, we characterized antibody responses in cattle
      experimentally infected with M. bovis. Sequential serum samples were collected
      every 3 to 4 weeks for up to 27 months postinfection. Circulating immunoglobulin
      G antibody levels were measured by an enzyme-linked immunosorbent assay using 12
      highly purified recombinant proteins of M. bovis. Six proteins, ESAT-6, 14-kDa
      protein, MPT63, MPT70, MPT51, and MPT32, were identified as major seroreactive
      antigens in bovine tuberculosis. A remarkable animal-to-animal variation of
      antigen recognition by serum antibodies was observed. Kinetic analyses of the
      antibody production to individual antigens during infection revealed that the
      heterogeneous antigen recognition profile changed markedly in a given infected
      animal as disease progressed.

PMID- 9784543
TI  - Complement activation in relation to capillary leakage in children with septic
      shock and purpura.
AB  - To assess the relationship between capillary leakage and inflammatory mediators
      during sepsis, blood samples were taken on hospital admission, as well as 24 and
      72 h later, from 52 children (median age, 3.3 years) with severe meningococcal
      sepsis, of whom 38 survived and 14 died. Parameters related to cytokines
      (interleukin 6 [IL-6] IL-8, plasma phospholipase A2, and C-reactive protein
      [CRP]), to neutrophil degranulation (elastase and lactoferrin), to complement
      activation (C3a, C3b/c, C4b/c, and C3- and C4-CRP complexes), and to complement
      regulation (functional and inactivated C1 inhibitor and C4BP) were determined.
      The degree of capillary leakage was derived from the amount of plasma infused and
      the severity of disease by assessing the pediatric risk of mortality (PRISM)
      score. Levels of IL-6, IL-8, C3b/c, C3-CRP complexes, and C4BP on admission,
      adjusted for the duration of skin lesions, were significantly different in
      survivors and nonsurvivors (C3b/c levels were on average 2.2 times higher in
      nonsurvivors, and C3-CRP levels were 1.9 times higher in survivors). Mortality
      was independently related to the levels of C3b/c and C3-CRP complexes. In
      agreement with this, levels of complement activation products correlated well
      with the PRISM score or capillary leakage. Thus, these data show that complement
      activation in patients with severe meningococcal sepsis is associated with a poor
      outcome and a more severe disease course. Further studies should reveal whether
      complement activation may be a target for therapeutical intervention in this
      disease.

PMID- 9784544
TI  - Helicobacter pylori lipopolysaccharide binds to CD14 and stimulates release of
      interleukin-8, epithelial neutrophil-activating peptide 78, and monocyte
      chemotactic protein 1 by human monocytes.
AB  - Helicobacter pylori gastritis is characterized by leukocyte infiltration of the
      gastric mucosa. The aims of this study were to determine whether H. pylori
      derived factors stimulate chemokine release from human monocytes and to ascertain
      whether H. pylori lipopolysaccharide (LPS) may be responsible for this effect.
      Human peripheral blood monocytes were exposed to an H. pylori water extract (HPE)
      or to purified H. pylori LPS. Levels of the chemokines interleukin-8 (IL-8),
      epithelial neutrophil-activating peptide 78 (ENA-78), and monocyte chemotactic
      protein 1 (MCP-1) were measured by enzyme-linked immunosorbent assay. The
      contribution of H. pylori LPS to monocyte activation was determined by using the
      LPS antagonist Rhodobacter sphaeroides lipid A (RSLA) and a blocking monoclonal
      antibody to CD14 (60bca). HPE increased monocyte secretion of IL-8, ENA-78, and
      MCP-1. Heat treatment of HPE did not reduce its ability to activate monocytes.
      Purified H. pylori LPS also stimulated monocyte chemokine production but was
      1,000-fold less potent than Salmonella minnesota lipid A. RSLA blocked H. pylori
      LPS-induced monocyte IL-8 release in a dose-dependent fashion (maximal inhibition
      82%, P < 0.001). RSLA also inhibited HPE-induced IL-8 release (by 93%, P <
      0.001). The anti-CD14 monoclonal antibody 60bca substantially inhibited IL-8
      release from HPE-stimulated monocytes (by 88%, P < 0.01), whereas the nonblocking
      anti-CD14 monoclonal antibody did not. These experiments with potent and specific
      LPS inhibitors indicate that the main monocyte-stimulating factor in HPE is LPS.
      H. pylori LPS, acting through CD14, stimulates human monocytes to release the
      neutrophil-activating chemokines IL-8 and ENA-78 and the monocyte-activating
      chemokine MCP-1. Despite its low relative potency, H. pylori LPS may play an
      important role in the pathogenesis of H. pylori gastritis.

PMID- 9784545
TI  - Fusion of Chlamydia trachomatis-containing inclusions is inhibited at low
      temperatures and requires bacterial protein synthesis.
AB  - The human pathogen Chlamydia trachomatis is an obligate intracellular bacterium
      with a unique developmental cycle. Within the host cell cytoplasm, it resides
      within a membrane-bound compartment, the inclusion. A distinguishing
      characteristic of the C. trachomatis life cycle is the fusion of the chlamydia
      containing inclusions with each other in the host cell cytoplasm. We report that
      fusion of inclusions does not occur at 32 degreesC in multiple mammalian cell
      lines and with three different serovars of C. trachomatis. The inhibition of
      fusion was inclusion specific; the fusion with sphingolipid-containing secretory
      vesicles and the interaction with early endosomes were unaffected by incubation
      at 32 degreesC. The inhibition of fusion of the inclusions was not primarily the
      result of delayed maturation of the inclusion, as infectious progeny was produced
      in host cells incubated at 32 degreesC, and the unfused inclusions remained
      competent to fuse up to 48 h postinfection. The ability to reverse the inhibition
      of fusion by shifting the infected cells from 32 to 37 degreesC allowed the
      measurement of the rate and the time of fusion of the inclusions after entry of
      the bacteria. Most significantly, we demonstrate that fusion of inclusions with
      each other requires bacterial protein synthesis and that the required bacterial
      protein(s) is present, but inactive or not secreted, at 32 degreesC.

PMID- 9784546
TI  - Mechanisms involved in the pathogenesis of sepsis are not necessarily reflected
      by in vitro cell activation studies.
AB  - It is thought that lipopolysaccharide (LPS) from gram-negative bacteria
      contributes significantly to the pathogenesis of septic shock. In vitro studies
      to address the mechanisms involved in this process have often investigated human
      monocytes or mouse macrophages, since these cells produce many of the mediators
      found in septic patients. Targeting of these mediators, especially tumor necrosis
      factor alpha (TNF-alpha), has been pursued as a means of reducing mortality in
      sepsis. Two experimental approaches were designed to test the assumption that in
      vitro studies with macrophages accurately predict in vivo mechanisms of LPS
      pathogenesis. In the first approach, advantage was taken of the fact that on
      consecutive days after injection of thioglycolate into mice, increased numbers of
      macrophages could be harvested from the peritoneum. These cells manifested
      markedly enhanced levels of in vitro TNF-alpha, interleukin 6 (IL-6), and nitric
      oxide production in response to LPS. In D-galactosamine-sensitized mice, however,
      thioglycolate treatment significantly decreased mortality due to LPS, as well as
      levels of circulating TNF-alpha and IL-6. Anti-TNF-alpha treatment confirmed this
      cytokine's role in the observed lethality. In a second experimental approach, we
      compared the mouse macrophage-stimulating potencies of different LPS preparations
      with their lethalities to mice. In these studies, the in vitro macrophage
      stimulating profiles presented by rough-LPS and smooth-LPS preparations were the
      reverse of their relative lethal potencies in vivo. In conclusion, peritoneal
      macrophages appear not to be the major cells responsible for the overall host
      response during endotoxic shock. These findings underscore the importance of
      verifying the correlation of in vivo systems with in vitro systems when
      attributing specific functions to a cell type.

PMID- 9784547
TI  - DbpA, but not OspA, is expressed by Borrelia burgdorferi during spirochetemia and
      is a target for protective antibodies.
AB  - DbpA is a target for antibodies that protect mice against infection by cultured
      Borrelia burgdorferi. Infected mice exhibit early and sustained humoral responses
      to DbpA and DbpB, suggesting that these proteins are expressed in vivo. Many
      antigens expressed in mammals by B. burgdorferi are repressed in vitro at lower
      growth temperatures, and we have now extended these observations to include DbpA
      and DbpB. To confirm that the protective antigen DbpA is expressed in vivo and to
      address the question of its accessibility to antibodies during infection, we
      examined B. burgdorferi in blood samples from mice following cutaneous
      inoculation. B. burgdorferi was visualized by dark-field microscopy in plasma
      samples from spirochetemic mice, and an indirect immunofluorescence assay showed
      that these spirochetes were DbpA positive and OspA negative. We developed an ex
      vivo borreliacidal assay to show that hyperimmune antiserum against DbpA, but not
      OspA, killed these plasma-derived spirochetes, demonstrating that DbpA is
      accessible to antibodies during this phase of infection. Blood transferred from
      spirochetemic donor mice readily established B. burgdorferi infection in naive
      recipient mice or mice hyperimmunized with OspA, while mice hyperimmunized with
      DbpA showed significant protection against challenge with host-adapted
      spirochetes. Antiserum from persistently infected mice had borreliacidal activity
      against both cultured and plasma-derived spirochetes, and adsorption of this
      serum with DbpA substantially depleted this killing activity. Our observations
      show that immunization with DbpA blocks B. burgdorferi dissemination from the
      site of cutaneous inoculation and suggest that DbpA antibodies may contribute to
      control of persistent infection.

PMID- 9784548
TI  - A streptococcal adhesion system for salivary pellicle and platelets.
AB  - A Streptococcus sanguis 133-79 adhesin identified by the monoclonal antibody 1.1
      (MAb 1.1) binds both saliva-coated hydroxylapatite (sHA) and platelets. The
      complementary binding site(s) for the adhesin was identified by the anti
      idiotypical MAb 2.1. To learn if this adhesion system, marked by the antiadhesin
      MAb 1.1 and anti-binding site MAb 2.1, is commonly used by strains within the
      sanguis group and other viridans group streptococci, 42 strains from seven
      species were tested. Strains that bind to both sHA and platelets use the same
      adhesin and binding site epitopes. Strains that do not adhere to platelets rely
      on other adhesin specificities to bind to sHA.

PMID- 9784549
TI  - Gene discovery through expressed sequence Tag sequencing in Trypanosoma cruzi.
AB  - Analysis of expressed sequence tags (ESTs) constitutes a useful approach for gene
      identification that, in the case of human pathogens, might result in the
      identification of new targets for chemotherapy and vaccine development. As part
      of the Trypanosoma cruzi genome project, we have partially sequenced the 5' ends
      of 1, 949 clones to generate ESTs. The clones were randomly selected from a
      normalized CL Brener epimastigote cDNA library. A total of 14.6% of the clones
      were homologous to previously identified T. cruzi genes, while 18.4% had
      significant matches to genes from other organisms in the database. A total of 67%
      of the ESTs had no matches in the database, and thus, some of them might be T.
      cruzi-specific genes. Functional groups of those sequences with matches in the
      database were constructed according to their putative biological functions. The
      two largest categories were protein synthesis (23.3%) and cell surface molecules
      (10.8%). The information reported in this paper should be useful for researchers
      in the field to analyze genes and proteins of their own interest.

PMID- 9784550
TI  - Impact of M49, Mrp, Enn, and C5a peptidase proteins on colonization of the mouse
      oral mucosa by Streptococcus pyogenes.
AB  - Resistance to phagocytosis is a hallmark of virulent Streptococcus pyogenes
      (group A streptococcus). Surface-bound C5a peptidase reduces recruitment of
      phagocytes to the site of infection, and hyaluronic acid capsules and/or the M
      protein limit the uptake of streptococci. In this study the relative impact of M
      and M-like proteins and the C5a peptidase on the virulence of a serotype M49
      strain was assessed. The capacities of isogenic strains with an insertion
      mutation in emm49; with a deletion mutation in scpA49 (C5a peptidase gene); and
      with a deletion that removes all three M-like genes, mrp49, emm49, and enn49, to
      colonize mice and resist phagocytosis were compared. Experiments confirmed
      results obtained in an earlier study, which showed that the M49 protein was not
      required for in vitro resistance to phagocytosis, and also showed that the M
      protein was not required for colonization of mice. Failure to produce all three M
      like proteins, M49, Mrp, and Enn49, significantly reduced the ability of these
      streptococci to resist phagocytosis in vitro but did not significantly alter the
      persistence of streptococci on the oral mucosa. In vitro experiments indicate
      that M+ streptococci are phagocytized by polymorphonuclear leukocytes that have
      been activated with phorbol-12-myristate 13-acetate or recombinant human C5a.
      This observation may explain the finding that expression of M49 protein is not
      essential for short-term colonization of the mouse oral mucosa.

PMID- 9784552
TI  - The repertoire of Anaplasma marginale antigens recognized by CD4(+) T-lymphocyte
      clones from protectively immunized cattle is diverse and includes major surface
      protein 2 (MSP-2) and MSP-3.
AB  - Major surface proteins of Anaplasma marginale are vaccine candidates. We recently
      demonstrated that immunization of calves with outer membranes of the Florida
      strain of A. marginale resulted in protective immunity that correlated with a
      memory CD4(+) T-lymphocyte response specific for major surface protein 1 (MSP-1),
      MSP-2, and MSP-3 (W. C. Brown, V. Shkap, D. Zhu, T. C. McGuire, W. Tuo, T. F.
      McElwain, and G. H. Palmer, Infect. Immun. 66:5406-5413, 1998). As immunogens,
      these proteins have been shown to induce complete or partial protection against
      homologous challenge. To further define the T helper (Th) cell response to these
      and other A. marginale antigens and to determine conservation of Th cell epitopes
      among genetically distinct A. marginale strains, Th cell clones obtained prior to
      challenge from three immunized calves were characterized for antigen-specific
      responses. Nine distinct antigenic profiles were defined by 11 Th cell clones
      derived by stimulation with the Florida strain. Several clones responded to MSP
      2, MSP-3, or both. All of these MSP-2- or MSP-3-specific clones and the majority
      of other clones that did not respond to MSPs recognized all bovine blood-passaged
      strains of A. marginale. These results demonstrate conservation of certain Th
      cell epitopes between MSP-2 and MSP-3 and show that Th cell epitopes in MSP-2,
      MSP-3, and undefined antigens are conserved among strains of A. marginale. Of
      seven clones that responded to the blood-passaged Virginia strain, two did not
      recognize antigen prepared from this strain cultured in tick cells, suggesting
      differences in the antigenic composition between these stages. Analysis of the
      cytokines expressed by the Th cells revealed that all clones expressed gamma
      interferon and tumor necrosis factor alpha, and most coexpressed interleukin-4.
      Our results provide a rationale for identifying Th cell epitopes conserved among
      different strains of A. marginale for inclusion in a nucleic acid or recombinant
      protein vaccine.

PMID- 9784551
TI  - CD4(+) T-lymphocyte and immunoglobulin G2 responses in calves immunized with
      Anaplasma marginale outer membranes and protected against homologous challenge.
AB  - Protective immunity against the ehrlichial pathogen Anaplasma marginale has been
      hypothesized to require induction of immunoglobulin G2 (IgG2) antibody against
      outer membrane protein epitopes and coordinated activation of macrophages for
      phagocytosis and killing. In the present study, cell-mediated immune responses,
      including induction of IgG isotype switching, were characterized in calves
      immunized with purified outer membranes of the Florida strain of A. marginale.
      Importantly, these calves were subsequently shown to be protected upon
      experimental challenge with the Florida strain, and calves which developed the
      highest IgG2 titers were completely protected against infection. Peripheral blood
      mononuclear cells (PBMC) obtained after immunization proliferated strongly in
      response to both whole A. marginale homogenates and purified outer membranes, and
      this responsiveness persisted until the time of challenge. Responding cells were
      shown to be CD4(+) T cells, and CD4(+) T-cell lines cultured for 2 to 4 weeks
      also proliferated specifically in response to A. marginale and produced high
      titers of gamma interferon. The helper T-cell response included recognition of
      conserved epitopes, as PBMC proliferation was stimulated by the homologous
      Florida strain, four genetically distinct A. marginale strains, and Anaplasma
      ovis. The outer membrane proteins stimulating the PBMC responses in protected
      calves included major surface proteins (MSPs) MSP-1, MSP-2, and MSP-3, which were
      previously shown to induce partial protection against infection. These studies
      demonstrate, for the first time, potent helper T-cell responses in cattle
      protectively immunized with outer membranes against A. marginale challenge and
      identify three MSPs that are recognized by immune T cells. These experiments
      provide the basis for subsequent identification of the helper T-cell epitopes on
      MSP-1, MSP-2, and MSP-3 that are needed to evoke anamnestic antibody and effector
      T-cell responses elicited by protein or nucleic acid immunization.

PMID- 9784554
TI  - Antibody response to fibronectin-binding adhesin FnbpA in patients with
      Staphylococcus aureus infections.
AB  - We have analyzed antibody reactivity to a fibronectin-binding microbial surface
      component that recognizes adhesive matrix molecules (MSCRAMM) in blood plasma
      collected from patients with staphylococcal infections. All patients had elevated
      levels of anti-MSCRAMM antibodies compared to those of young children who,
      presumably, had not been exposed to staphylococcal infections. The anti-MSCRAMM
      antibodies preferentially reacted with the ligand-binding repeat domain of the
      adhesin. However, these antibodies did not inhibit fibronectin binding.
      Essentially, all patients had antibodies which specifically recognized the
      fibronectin-MSCRAMM complex but not the isolated components. Epitopes recognized
      by these anti-ligand-induced binding sites antibodies were found in each repeat
      unit of the MSCRAMM. These results demonstrate that staphylococci have bound
      fibronectin some time during infection and that each repeat unit in the MSCRAMM
      can engage in ligand binding. Furthermore, our previously proposed model,
      suggesting that an unordered structure in the MSCRAMM undergoes a conformational
      change upon ligand binding (K. House-Pompeo, Y. Xu, D. Joh, P. Speziale, and M.
      Hook, J. Biol. Chem. 271:1379-1384, 1996), is presumably operational in patients
      during infections.

PMID- 9784553
TI  - DNA and a CpG oligonucleotide derived from Babesia bovis are mitogenic for bovine
      B cells.
AB  - DNAs from bacteria and variety of nonvertebrate organisms, including nematodes,
      mollusks, yeasts, and insects, cause polyclonal activation of murine B
      lymphocytes. Similar studies have not been reported for bovine B cells, and to
      date no studies have reported mitogenic properties of protozoal DNA for any
      species. However, we and others have observed that protozoal parasite antigens
      can induce the proliferation of lymphocytes from nonexposed donors. Extending
      these studies, we now show that the mitogenic property of protozoal antigen
      preparations is in part attributable to parasite DNA and that Babesia bovis DNA
      is directly mitogenic for bovine B cells. DNase treatment of B. bovis extracts
      abrogated B. bovis-induced proliferation of peripheral blood mononuclear cells
      from nonexposed cattle. Like DNAs from other organisms that were mitogenic for
      murine B cells, B. bovis DNA is largely nonmethylated and induced a dose
      dependent proliferation of bovine B cells, which was reduced upon methylation.
      Furthermore, B. bovis and E. coli DNAs enhanced immunoglobulin secretion by
      cultured B cells, inducing moderate increases in immunoglobulin G1 and stronger
      increases in immunoglobulin G2. Because certain nonmethylated CpG motifs present
      in bacterial DNA are known to stimulate proliferation of murine and human B
      cells, an 11-kb fragment of B. bovis DNA was analyzed for CG dinucleotide content
      and for the presence of known immunostimulatory sequences (ISS) centered on a CG
      motif. The frequency of CG dinucleotides was approximately one-half of the
      expected frequency, and several CpG hexameric sequences with known activity for
      murine B cells were identified. An oligodeoxynucleotide containing one of these
      ISS (AACGTT), which is present within the rhoptry-associated protein-1 (rap-1)
      open reading frame, was shown to stimulate B-cell proliferation. These ISS may be
      involved in host immune modulation during protozoal infection and may be useful
      as vaccine adjuvants.

PMID- 9784555
TI  - Immunogenicity and protective efficacy of the WI-1 adhesin of Blastomyces
      dermatitidis.
AB  - People infected with Blastomyces dermatitidis develop strong immunity to the
      yeast surface adhesin WI-1, including antibody responses to the adhesive domain,
      a 25-amino-acid repeat, and cellular responses to the N terminus. We studied the
      immunogenicity of WI-1 and the ability of anti-WI-1 immune responses to protect
      against lethal pulmonary infection in mice. WI-1 immunization, given in Freund's
      adjuvant subcutaneously in two doses 2 weeks apart, evoked delayed
      hypersensitivity responses in a concentration-dependent manner. Immunized mice
      also had anti-WI-1 antibody responses, with titers reaching an endpoint dilution
      of approximately 1:800,000. Anti-WI-1 immunoglobulin G (IgG) antibody subclasses
      were IgG1 > IgG2b > IgG2a > IgG3, indicating a mixed T helper 1 and T helper 2
      immune response. In protection experiments, WI-1 immunization significantly
      prolonged the survival of C57BL/6 and BALB/c mice compared to controls following
      intranasal administration of a lethal dose of B. dermatitidis yeasts (Kaplan
      Meier survival curve P values of 0.027 to 0.0002) and also protected a proportion
      of the animals from death due to progressive pulmonary blastomycosis. Taken
      together, our results suggest that administration of WI-1 raises antibody and
      cell-mediated immune responses, which enhance resistance against pulmonary
      infection with B. dermatitidis. Mechanisms of vaccine-induced resistance require
      further investigation.

PMID- 9784556
TI  - Murine immune responses to Neisseria meningitidis group C capsular polysaccharide
      and a thymus-dependent toxoid conjugate vaccine.
AB  - The polysaccharide (PS) capsules of many pathogenic bacteria are poor immunogens
      in infants and young children as a result of the delayed response to PS antigens
      during ontogeny. The development of polysaccharide-protein conjugate vaccines for
      Haemophilus influenzae type b, which have proven to be efficacious in this age
      group, has led to active development by a number of investigators of conjugate
      vaccines for other diseases. We describe here the response of several mouse
      strains to the capsular PS of Neisseria meningitidis group C (MCPS) conjugated to
      tetanus toxoid (MCPS-TT) and the same response in BALB/c mice as a model of the
      immune consequences of conjugate vaccine immunization. The use of a conjugate
      vaccine results in a shift in the isotype elicited in response to the MCPS, from
      immunoglobulin M (IgM) and IgG3 to primarily IgG1. A response to MCPS-TT is seen
      even among mouse strains which respond poorly to MCPS itself, emphasizing the
      importance of a strain survey when choosing a mouse model for a vaccine. The
      marked increase in IgG1 antibody titer was accompanied by a large increase in
      bactericidal activity of sera from these animals. Animals primed with the
      conjugate vaccine demonstrated a booster response after secondary immunization
      with either the MCPS or the conjugate. The ability to produce a boosted IgG1 anti
      MCPS response to the MCPS can be transferred to adoptive recipients by B cells
      alone from mice primed with MCPS-TT but not mice primed with MCPS alone. These
      data indicate that in BALB/c mice a single immunization with MCPS-TT is
      sufficient to induce a shift to IgG1 and generate a memory B-cell population that
      does not require T cells for boosting.

PMID- 9784557
TI  - Gamma interferon production by cytotoxic T lymphocytes is required for resolution
      of Chlamydia trachomatis infection.
AB  - In this study, we used mice in which the gene for gamma interferon (IFN-gamma)
      has been disrupted (IFN-gamma-/- mice) to study the role of this cytokine in the
      resolution of Chlamydia trachomatis infection. We show that IFN-gamma-/- mice are
      impaired in the ability to clear infection with C. trachomatis compared to IFN
      gamma+/+ control mice. Activated CD8(+) cytotoxic T lymphocytes (CTL) secrete IFN
      gamma in response to intracellular infection, and we have shown previously that a
      Chlamydia-specific CTL line can reduce C. trachomatis infection when adoptively
      transferred into infected mice. In the present study, we found that when these
      IFN-gamma+/+ CTL lines are transferred into Chlamydia-infected IFN-gamma-/- mice,
      the transferred CTL cannot overcome the immune defect seen in the IFN-gamma-/-
      mice. We also show that Chlamydia-specific CTL can be cultured from IFN-gamma
      deficient mice infected with C. trachomatis; however, the adoptive transfer of
      IFN-gamma-/- CTL into infected IFN-gamma+/+ mice does not reduce the level of
      infection. These results suggest that IFN-gamma production by CTL is not
      sufficient to overcome the defect that IFN-gamma-/- mice have in the resolution
      of Chlamydia infection, yet IFN-gamma production by CTL is required for the
      protective effect seen upon adoptive transfer of CTL into IFN-gamma+/+ mice.

PMID- 9784558
TI  - Effect of Clostridium difficile toxin A on human colonic lamina propria cells:
      early loss of macrophages followed by T-cell apoptosis.
AB  - We have previously shown that Clostridium difficile toxin A induces detachment of
      human colonic epithelial cells from the basement membrane and subsequent cell
      death by apoptosis. Because these cells require adhesion-dependent signalling
      from the extracellular matrix for survival, their detachment from the basement
      membrane by other means also induces apoptosis. The role of toxin A in the
      induction of apoptosis therefore remains to be determined. In addition,
      sensitivities to C. difficile toxin A of lamina propria lymphocytes, macrophages,
      and eosinophils, which lie below the surface epithelium, are not known. In
      contrast to epithelial cells, these lamina propria cells do not require adhesion
      dependent signalling from the extracellular matrix for survival, and this may
      allow the mechanisms of toxin A-induced cell death to be further investigated.
      The aim of this study was to investigate the effect of purified C. difficile
      toxin A on human colonic lamina propria T cells, macrophages, and eosinophils. We
      show that C. difficile toxin A induces loss of viability in isolated colonic
      lamina propria cell preparations containing the three different cell types in a
      dose- and time-dependent fashion. Exposure to high concentrations of the toxin
      led to loss of macrophages within 72 h. T-lymphocyte and eosinophil cell death
      was prominent at later time points and occurred by apoptosis. Exposure to toxin A
      also induced the production of tumor necrosis factor alpha by the isolated
      colonic lamina propria cells. However, the presence of neutralizing antibodies to
      this cytokine did not influence C. difficile toxin A-induced T-cell apoptosis.
      Moreover, purified T cells also underwent apoptosis following exposure to toxin
      A, implying that apoptosis occurred as a consequence of a direct interaction
      between T cells and the toxin. Our studies suggest that C. difficile toxin A is
      capable of suppressing human colonic mucosal immune responses by inducing early
      loss of macrophages followed by T-cell apoptosis.

PMID- 9784559
TI  - Oral immunization with a Salmonella typhimurium vaccine vector expressing
      recombinant enterotoxigenic Escherichia coli K99 fimbriae elicits elevated
      antibody titers for protective immunity.
AB  - Bovine enterotoxigenic Escherichia coli (ETEC) continues to cause mortality in
      piglets and newborn calves. In an effort to develop a safe and effective vaccine
      for the prevention of F5(+) ETEC infections, a balanced lethal asd+ plasmid
      carrying the complete K99 operon was constructed and designated pMAK99-asd+.
      Introduction of this plasmid into an attenuated Salmonella typhimurium Deltaaro
      Deltaasd strain, H683, resulted in strain AP112, which stably expresses E. coli
      K99 fimbriae. A single oral immunization of BALB/c and CD-1 mice with strain
      AP112 elicited significant mucosal immunoglobulin A (IgA) titers that remained
      elevated for >11 weeks. IgA and IgG responses in serum specific for K99 fimbriae
      were also induced, with a prominent IgG1, as well as IgG2a and IgG2b, titer. To
      assess the derivation of these antibodies, a K99 isotype-specific B-cell ELISPOT
      analysis was conducted by using mononuclear cells from the lamina propria of the
      small intestines (LP), Peyer's patches (PP), and spleens of vaccinated and
      control BALB/c mice. This analysis revealed elevated numbers of K99 fimbria
      specific IgA-producing cells in the LP, PP, and spleen, whereas elevated K99
      fimbria-specific IgG-producing cells were detected only in the PP and spleen.
      These antibodies were important for protective immunity. One-day-old neonates
      from dams orally immunized with AP112 were provided passive protection against
      oral challenge with wild-type ETEC, in contrast to challenged neonates from
      unvaccinated dams or from dams vaccinated with a control Salmonella vector. These
      results confirm that oral Salmonella vaccine vectors effectively deliver K99
      fimbriae to mucosal inductive sites for sustained elevation of IgA and IgG
      antibodies and for eliciting protective immunity.

PMID- 9784560
TI  - SCID/NCr mice naturally infected with Helicobacter hepaticus develop progressive
      hepatitis, proliferative typhlitis, and colitis.
AB  - Hepatitis, proliferative typhlitis, and colitis were characterized in young adult
      and older SCID/NCr mice naturally infected with Helicobacter hepaticus. Liver
      lesions consisted of Kupffer, Ito, and oval cell hyperplasia along with
      multifocal to coalescing coagulative hepatocyte necrosis. Numerous Warthin-Starry
      positive bacteria were observed in the parenchyma, and there were minimal to mild
      accumulations of monocytic cells and neutrophils. Proliferative typhlitis was
      characterized by moderate to marked mucosal epithelial cell hyperplasia with mild
      monocytic and neutrophilic infiltration. Minimal to mild colitis with mucosal
      epithelial cell hyperplasia of the colon was most marked in older mice.
      Comparable gastrointestinal lesions were not observed in uninfected control
      SCID/NCr mice. H. hepaticus was cultured from fetal viscera of 2 of 11 pups
      sampled late in gestation from infected SCID/NCr females, suggesting
      transplacental infection of H. hepaticus. As expected, most of the naturally
      infected SCID/NCr mice had no serum immunoglobulin G response against H.
      hepaticus. These findings contrast with those in infected immunocompetent A/JCr
      mice, which develop a significant immune response to H. hepaticus associated with
      prominent multifocal mononuclear cell infiltrates in the liver, with only rare
      bacteria observable at the periphery of inflammatory foci or in the biliary
      canaliculi. The results demonstrate that chronic inflammatory and proliferative
      lesions simultaneously affecting the liver, cecum, and colon are associated with
      natural infection of SCID/NCr mice with H. hepaticus and that lesions are
      progressive with age. Concurrent infection with H. hepaticus may confound studies
      that have been attributed to similar lesions due to other experimental
      manipulations of SCID/NCr mice.

PMID- 9784562
TI  - High-level expression of Chlamydia psittaci major outer membrane protein in COS
      cells and in skeletal muscles of turkeys.
AB  - The omp1 genes encoding the major outer membrane proteins (MOMPs) of avian
      Chlamydia psittaci serovar A and D strains were cloned and sequenced. The
      nucleotide sequences of the avian C. psittaci serovar A and D MOMP genes were
      found to be 98.9 and 87.8% identical, respectively, to that of the avian C.
      psittaci serovar A strain 6BC, 84.6 and 99.8% identical to that of the avian C.
      psittaci serovar D strain NJ1, 79.1 and 81.1% identical to that of the C.
      psittaci guinea pig inclusion conjunctivitis strain, 60.9 and 62.5% identical to
      that of the Chlamydia trachomatis L2 strain, and 57.5 and 60.4% identical to that
      of the Chlamydia pneumoniae IOL-207 strain. The serovar A or D MOMPs were cloned
      in the mammalian expression plasmid pcDNA1. When pcDNA1/MOMP A or pcDNA1/MOMP D
      was introduced into COS7 cells, a 40-kDa protein that was identical in size,
      antigenicity, and electrophoretic mobility to native MOMP was produced.
      Recombinant MOMP (rMOMP) was located in the cytoplasm of transfected COS7 cells
      as well as in the plasma membrane and was immunoaccessible. Intramuscular
      administration of pcDNA1/MOMP in specific-pathogen-free turkeys resulted in local
      expression of rMOMP in its native conformation, after which anti-MOMP antibodies
      appeared in the serum.

PMID- 9784561
TI  - Identification of the perosamine synthetase gene of Brucella melitensis 16M and
      involvement of lipopolysaccharide O side chain in Brucella survival in mice and
      in macrophages.
AB  - Brucella organisms are facultative intracellular bacteria that may infect many
      species of animals as well as humans. The smooth lipopolysaccharide (S-LPS) has
      been reported to be an important virulence factor of these organisms, but the
      genetic basis of expression of the S-LPS O antigen has not yet been described.
      Likewise, the role of the O side chain of S-LPS in the survival of Brucella has
      not been clearly defined. A mini-Tn5 transposon mutant library of Brucella
      melitensis 16M was screened by enzyme-linked immunosorbent assay (ELISA) with
      monoclonal antibodies (MAbs) directed against the O side chain of Brucella. One
      mutant, designated B3B2, failed to express any O side chain as confirmed by
      ELISA, Western blot analysis, and colony coloration with crystal violet.
      Nucleotide sequence analysis demonstrated that the transposon disrupted an open
      reading frame with significant homology to the putative perosamine synthetase
      genes of Vibrio cholerae O1 and Escherichia coli O157:H7. The low G+C content of
      this DNA region suggests that this gene may have originated from a species other
      than a Brucella sp. The survival of B. melitensis mutant strain B3B2 in the mouse
      model and in bovine macrophages was examined. The results suggested that S-LPS
      or, more precisely, its O side chain is essential for survival in mice but not in
      macrophages.

PMID- 9784564
TI  - Role of gamma delta T cells in immunopathology of pulmonary Mycobacterium avium
      infection in mice.
AB  - Several studies have shown that gamma delta T cells influence granuloma
      development after infection with intracellular pathogens. The role of gamma delta
      T cells in controlling the influx of inflammatory cells into the lung after
      Mycobacterium avium infection was therefore examined with gene-disrupted mice
      (K/O). The mice were infected with either M. avium 724, a progressively
      replicating highly virulent strain of M. avium, or with M. avium 2-151 SmT, a
      virulent strain that induces a chronic infection. gamma delta-K/O mice infected
      with M. avium 2-151 SmT showed early enhanced bacterial growth within the lung
      compared to the wild-type mice, although granuloma formation was similar in both
      strains. gamma delta-K/O mice infected with M. avium 724 showed identical
      bacterial growth within the lung compared to the wild-type mice, but they
      developed more-compact lymphocytic granulomas and did not show the extensive
      neutrophil influx and widespread tissue necrosis seen in wild-type mice. These
      data support the hypothesis that isolates of M. avium that induce protective T
      cell-specific immunity are largely unaffected by the absence of gammadelta T
      cells. Whereas with bacterial strains that induce poor protective immunity, the
      absence of gamma delta T cells led to significant reductions in both the influx
      of neutrophils and tissue damage within the lungs of infected mice.

PMID- 9784563
TI  - The EspB protein of enteropathogenic Escherichia coli is targeted to the
      cytoplasm of infected HeLa cells.
AB  - The EspB protein of enteropathogenic Escherichia coli (EPEC) is exported via a
      type III secretion apparatus. EspB is critical for signaling the host cell and
      for the development of the attaching and effacing lesion characteristic of EPEC
      infection. We used cellular fractionation and confocal laser scanning microscopy
      to determine the cellular location of EspB during infection of HeLa cells. Both
      methods indicated that EspB is targeted to the cytoplasm of infected cells. Using
      mutants, we found that EspB targeting to the host cell cytoplasm requires the
      type III secretion apparatus and the secreted proteins EspA and EspD, but not
      intimin. These results provide insights into the function of the type III
      secretion apparatus of EPEC and the functions of the Esp proteins.

PMID- 9784565
TI  - Transmission and serial propagation of Enterocytozoon bieneusi from humans and
      Rhesus macaques in gnotobiotic piglets.
AB  - For over a decade Enterocytozoon bieneusi infections in people with AIDS have
      been linked with chronic diarrhea and wasting. The slow scientific progress in
      treating these infections is attributed to the inability of investigators to
      cultivate the parasite, which has also precluded evaluation of effective
      therapies. We report here successful serial transmissions of E. bieneusi from
      patients with AIDS and from macaques with AIDS to immunosuppressed gnotobiotic
      piglets. One infected piglet was still excreting spores at necropsy 50 days after
      an oral challenge. Spores in feces were detected microscopically by trichrome
      stain and by PCR and within enterocytes by in situ hybridization and
      immunohistochemistry. E. bieneusi infection induced no symptoms. The development
      of an animal model for E. bieneusi will open up new opportunities for
      investigating this parasite.

PMID- 9784566
TI  - Nitric oxide synthase expression in macrophages of Histoplasma capsulatum
      infected mice is associated with splenocyte apoptosis and unresponsiveness.
AB  - Splenic macrophages from Histoplasma capsulatum-infected mice express inducible
      nitric oxide synthase (iNOS), and the iNOS expression correlates with severity of
      the infection. We examined whether production of NO is responsible for apoptosis
      and the anti-lymphoproliferative response of splenocytes from mice infected with
      H. capsulatum. In situ terminal deoxynucleotidyl transferase nick end labeling
      revealed apoptotic nuclei in cryosections of spleen from infected but not normal
      mice. Splenocytes of infected mice were unresponsive to stimulation by either
      concanavalin A or heat-killed H. capsulatum yeast cells. Splenocyte
      responsiveness was restored by addition to the medium of NG-monomethyl-L
      arginine, a known inhibitor of NO production. The proliferative response of
      splenocytes from infected mice was also restored by depletion of macrophages or
      by replacement with macrophages from normal mice. In addition, expression of iNOS
      returned to its basal level when the animals had recovered from infection. These
      results suggest that suppressor cell activity of macrophages is associated with
      production of NO, which also appears to be an effector molecule for apoptosis of
      cultured splenocytes from infected mice.

PMID- 9784568
TI  - Murine model of Bartonella henselae infection in the immunocompetent host.
AB  - Bartonella henselae is an emerging pathogen causing cat scratch disease,
      bacillary angiomatosis, and peliosis hepatis. Progress in understanding the
      pathogenesis of and the immune response to these infections has been limited by
      the lack of an animal model. Following intraperitoneal infection of C57BL/6 mice
      with B. henselae, organs were cleared of cultivatable bacteria within 6 days. In
      contrast, B. henselae DNA could be detected in liver tissue for at least 3
      months. Liver tissue showed granulomatous inflammation reaching its highest
      degree of intensity during the fourth week of infection and resolving within 12
      weeks postinfection. This mouse model is applicable to the study of the
      pathogenesis of B. henselae and the immune response to this pathogen in the
      immunocompetent host.

PMID- 9784567
TI  - Coxiella burnetii induces reorganization of the actin cytoskeleton in human
      monocytes.
AB  - Coxiella burnetii, an obligate intracellular bacterium which survives in myeloid
      cells, causes Q fever in humans. We previously demonstrated that virulent C.
      burnetii organisms are poorly internalized by monocytes compared to avirulent
      variants. We hypothesized that a differential mobilization of the actin
      cytoskeleton may account for this distinct phagocytic behavior. Scanning electron
      microscopy demonstrated that virulent C. burnetii stimulated profound and
      polymorphic changes in the morphology of THP-1 monocytes, consisting of membrane
      protrusions and polarized projections. These changes were transient, requiring 5
      min to reach their maximum extent and vanishing after 60 min of incubation. In
      contrast, avirulent variants of C. burnetii did not induce any significant
      changes in cell morphology. The distribution of filamentous actin (F-actin) was
      then studied with a specific probe, bodipy phallacidin. Virulent C. burnetii
      induced a profound and transient reorganization of F-actin, accompanied by an
      increase in the F-actin content of THP-1 cells. F-actin was colocalized with
      myosin in cell protrusions, suggesting that actin polymerization and the tension
      of actin-myosin filaments play a role in C. burnetii-induced morphological
      changes. In addition, contact between the cell and the bacterium seems to be
      necessary to induce cytoskeleton reorganization. Bacterial supernatants did not
      stimulate actin remodeling, and virulent C. burnetii organisms were found in
      close apposition with F-actin protrusions. The manipulation of the actin
      cytoskeleton by C. burnetii may therefore play a critical role in the
      internalization strategy of this bacterium.

PMID- 9784570
TI  - Antrum- and corpus mucosa-infiltrating CD4(+) lymphocytes in Helicobacter pylori
      gastritis display a Th1 phenotype.
AB  - In this study, cytokine patterns produced by CD4(+) T cells isolated from antrum
      or corpus gastral biopsy specimens of 10 patients with Helicobacter pylori
      positive gastritis were compared. To this end, expression of intracellular
      cytokines (interleukin-4 [IL-4] and gamma interferon) and of CD4 was assessed by
      flow cytometry. Ten to 60% of the isolated CD4(+) T cells produced gamma
      interferon upon stimulation. With the exception of one patient, IL-4-positive
      CD4(+) cells were not detected. Therefore, CD4(+) cells infiltrating antrum and
      corpus stomach mucosa during H. pylori infection show a Th1 phenotype. This
      polarized Th1-type response may contribute to the inability of the immune system
      to eradicate H. pylori infection.

PMID- 9784569
TI  - Protection by CD4 or CD8 T cells against pulmonary Mycobacterium bovis bacillus
      Calmette-Guerin infection.
AB  - Mice deficient in CD8 T cells demonstrated levels of Th1 cytokines and
      granulomatous responses in the lungs very similar to those demonstrated by normal
      control mice and were fully capable of controlling pulmonary mycobacterial
      infection by Mycobacterium bovis BCG as assessed at day 37 postinfection. In
      comparison, mice deficient in CD4 T cells had similar levels of interleukin-12
      (IL-12) and tumor necrosis factor alpha but lower levels of gamma interferon in
      the lungs and were still able to mount tissue granulomatous responses and control
      pulmonary mycobacterial infection. In contrast, IL-12(-/-) mice with impaired CD4
      and CD8 T-cell responses had a markedly weakened control of infection, whereas
      SCID mice deficient in all T cells succumbed to such pulmonary mycobacterial
      infections.

PMID- 9784571
TI  - Deletion of the major proteolytic site of the Helicobacter pylori cytotoxin does
      not influence toxin activity but favors assembly of the toxin into hexameric
      structures.
AB  - The Helicobacter pylori cytotoxin is proteolytically cleaved at a flexible
      hydrophilic loop into two subunits. Deletion of the loop sequences had no effect
      on biological activity of the toxin in the HeLa cell vacuolation assay but
      favored the organization of the protein into hexameric rather than heptameric
      structures.

PMID- 9784572
TI  - Protection against exotoxin A (ETA) and Pseudomonas aeruginosa infection in mice
      with ETA-specific antipeptide antibodies.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen that causes serious and
      sometimes fatal infections in the compromised host, especially in patients with
      major trauma or thermal injuries. Exotoxin A (ETA) is the major and most lethal
      virulence factor produced by this ubiquitous microorganism. In a recent study (H.
      S. Elzaim, A. K. Chopra, J. W. Peterson, R. Goodheart, and J. P. Heggers, Infect.
      Immun. 66:2170-2179, 1998), we identified two major epitopes, one within the
      translocation domain (amino acid [aa] residues 289 to 333) of ETA and another
      within the enzymatic domain (aa 610 to 638), by using a panel of antipeptide
      antibodies. Synthetic peptides representing these two epitopes induced ETA
      specific antibodies which were able to abrogate the cytotoxic activity of ETA, as
      measured by incorporation of [3H]leucine into 3T3 fibroblasts. In the present
      study, these antibodies were tested for the ability to provide protection against
      ETA and infection with a toxin-producing strain of P. aeruginosa in a mouse
      model. Antibodies to either of the synthetic peptides conferred protection
      against ETA. Also, when used for immunization, both peptides induced active
      immunity to ETA in mice. Antibodies to the peptide representing a region within
      the enzymatic domain of ETA, in combination with the antibiotic amikacin,
      enhanced the survival of mice infected with a toxin-producing strain of P.
      aeruginosa. Thus, antipeptide antibodies specific for ETA might be paired with
      antibiotic treatment for passive immunization of patients suffering from P.
      aeruginosa infection.

PMID- 9784573
TI  - Diversity in protein synthesis and viability of Helicobacter pylori coccoid forms
      in response to various stimuli.
AB  - The viability of the coccoid forms of Helicobacter pylori was evaluated by
      assessing protein synthesis. Metabolic labeling studies showed the synthesis of
      proteins and the specific protein profiles of H. pylori coccoids produced under
      various conditions. Harsh conditions such as aerobiosis and starvation (lack of
      horse serum) in the culture did not affect the synthesis of proteins in the
      coccoids. Lowering of the pH to that of gastric secretions induced expression of
      several proteins in the coccoids. However, the coccoids produced under prolonged
      microaerobic conditions exhibited a profile of acid stress-induced protein
      expression different from that induced by aerobiosis or starvation. Our data
      suggest that coccoid H. pylori exhibits diversity in viability following exposure
      to different stresses and that the response to acid stress of coccoid H. pylori
      could be involved in infection of the host stomach.

PMID- 9784574
TI  - Effect of P39 gene deletion in live Brucella vaccine strains on residual
      virulence and protective activity in mice.
AB  - The 39-kilodalton protein (P39) has previously been shown to be an immunodominant
      protein in Brucella infections. P39 gene deletion mutants of vaccine strains
      Brucella abortus S19 and Brucella melitensis Rev.1 were constructed by gene
      replacement. This deletion did not significantly modify the residual virulence of
      both vaccine strains in CD-1 mice. CD-1 mice vaccinated with the parent or mutant
      strains were protected against a virulent challenge. Mutant vaccine strains
      devoid of P39 could provide a means for differentiating vaccinated from infected
      animals.

PMID- 9784575
TI  - Structural and antigenic characteristics of Streptococcus sobrinus glucan binding
      proteins.
AB  - Three purified glucan binding proteins (GBP-2, GBP-3, and GBP-5) from
      Streptococcus sobrinus 6715 were compared structurally by mass spectroscopy of
      tryptic fragments and antigenically by Western blot analysis with rat antisera to
      each GBP or to peptides containing putative glucan binding epitopes of mutans
      streptococcal glucosyltransferases. Structural and antigenic analyses indicated
      that GBP-3 and GBP-5 are very similar but that both are essentially unrelated to
      GBP-2. None of these S. sobrinus GBPs appeared to have a strong antigenic
      relationship with GBPs from Streptococcus mutans. Thus, S. sobrinus GBP-2 and GBP
      3 appear to be distinct proteins with potentially different functions. S.
      sobrinus GBP-5 may be a proteolytic fragment of GBP-3, or, alternatively, the
      genes coding for these proteins may be closely related.

PMID- 9784576
TI  - A protein (M9) associated with monoclonal antibody-mediated agglutination of
      Mycoplasma gallisepticum is a member of the pMGA family.
AB  - A 62-kDa cell surface antigen (M9) of Mycoplasma gallisepticum PG31 that mediates
      antibody-induced agglutination of the organism was purified and subjected to N
      terminal amino-acid sequencing. A 999-bp region of the cDNA encoding the M9
      protein was generated by reverse transcription-PCR, and its nucleotide sequence
      was determined. PCR primers based on this sequence were used to screen a genomic
      DNA library of PG31. A full-length M9 protein-encoding gene was isolated and
      sequenced, revealing 96% nucleotide identity with the pMGA1.1 gene of M.
      gallisepticum S6. Sequence analyses of the M9 gene and flanking open reading
      frames that encode other pMGA family members suggest that a tandemly repeated GAA
      sequence may influence pMGA gene expression.

PMID- 9784577
TI  - Characterization of a 34-kilodalton protein of Mycobacterium leprae that is
      isologous to the immunodominant 34-kilodalton antigen of Mycobacterium
      paratuberculosis.
AB  - During DNA sequence analysis of cosmid L373 from the Mycobacterium leprae genome,
      an open reading frame of 1.4 kb encoding a protein with some homology to the
      immunodominant 34-kDa protein of Mycobacterium paratuberculosis, but lacking
      significant serological activity, was detected. The DNA sequence predicted a
      signal peptide with a modified lipoprotein consensus sequence, but the protein
      proved to be devoid of lipid attachment.

PMID- 9784578
TI  - Translocated intimin receptors (Tir) of Shiga-toxigenic Escherichia coli isolates
      belonging to serogroups O26, O111, and O157 react with sera from patients with
      hemolytic-uremic syndrome and exhibit marked sequence heterogeneity.
AB  - The capacity to form attaching and effacing (A/E) lesions on the surfaces of
      enterocytes is an important virulence trait of several enteric pathogens,
      including enteropathogenic Escherichia coli (EPEC) and Shiga-toxigenic E. coli
      (STEC). Formation of such lesions depends upon an interaction between a bacterial
      outer membrane protein (intimin) and a bacterially encoded receptor protein (Tir)
      which is exported from the bacterium and translocated into the host cell
      membrane. Intimin, Tir, and several other proteins necessary for generation of
      A/E lesions are encoded on a chromosomal pathogenicity island termed the locus
      for enterocyte effacement (LEE). Reports of sequence heterogeneity and antigenic
      variation in the region of intimin believed to be responsible for receptor
      binding raise the possibility that the receptor itself is also heterogeneous. We
      have examined this by cloning and sequencing tir genes from three different STEC
      strains belonging to serogroups O26, O111, and O157. The deduced amino acid
      sequences for the Tir homologues from these strains varied markedly, exhibiting
      only 65.4, 80.2, and 56.7% identity, respectively, to that recently reported for
      EPEC Tir. STEC Tir is also highly immunogenic in humans. Western blots of E. coli
      DH5alpha expressing the various STEC tir genes cloned in pBluescript [but not E.
      coli DH5alpha(pBluescript)] reacted strongly with convalescent sera from patients
      with hemolytic-uremic syndrome (HUS) caused by known LEE-positive STEC. Moreover,
      no reaction was seen when the various clone lysates were probed with serum from a
      patient with HUS caused by a LEE-negative STEC or with serum from a healthy
      individual. Covariation of exposed epitopes on both intimin and Tir may be a
      means whereby STEC avoid host immune responses without compromising adhesin
      receptor interaction.

PMID- 9784579
TI  - Morphological transition of Paracoccidioides brasiliensis conidia to yeast cells:
      in vivo inhibition in females.
AB  - Clinical paracoccidioidomycosis is 13 times more common in men than in women.
      Estrogen inhibits the transition of mycelia or conidia (the saprophytic form of
      Paracoccidioides brasiliensis) to yeasts (the parasitic form) in vitro. Here, we
      show that, in male mice that were infected intranasally (mimicking natural
      infection) the transition of conidia in bronchoalveolar lavage fluids to
      intermediate forms and yeasts occurred over 24 to 96 h; CFU and yeasts (shown by
      histopathology) increased subsequently. In females, transition did not occur and
      infection cleared. These events in vivo are consistent with epidemiological and
      in vitro observations, suggesting that female hormones block transition and are
      responsible for resistance.

PMID- 9784582
TI  - Maintenance of acidic lateral intercellular spaces by endogenous fixed buffers in
      MDCK cell epithelium.
AB  - The lateral intercellular spaces (LIS) of MDCK cell epithelia grown on permeable
      supports are about 0.4 pH units acidic to the bathing solutions, presumably
      because of buffering by the fixed negative charges on the surface of the lateral
      cell membranes. To test the hypothesis that fixed buffers are responsible for the
      acidity, a theoretical and experimental approach was developed for the
      determination of the concentration and pK of the fixed buffer constituted by the
      glycocalyx. The pH of the solution in the LIS was measured by ratiometric
      fluorescence microscopy while the buffer concentration or composition of the
      bathing solutions was altered. In addition, the divalent cation Sr2+ was added to
      the perfusion solutions to displace protons from the fixed buffer sites for the
      determination of the fixed buffer properties. We conclude that the LIS contain
      3.7 mm of pK 6.2 fixed buffer and that this buffer is responsible for the acidic
      microenvironment in the LIS.

PMID- 9784581
TI  - Sequence analyses and phylogenetic characterization of the ZIP family of metal
      ion transport proteins.
AB  - Several novel but similar heavy metal ion transporters, Zrt1, Zrt2, Zip1-4 and
      Irt1, have recently been characterized. Zrt1, Zrt2 and Zip1-4 are probably zinc
      transporters in Saccharomyces cerevisiae and Arabidopsis thaliana whereas Irt1
      appears to play a role in iron uptake in A. thaliana. The family of proteins
      including these functionally characterized transporters has been designated the
      Zrt- and Irt-related protein (ZIP) family. In this report, ZIP family proteins in
      the current databases were identified and multiply aligned, and a phylogenetic
      tree for the family was constructed. A family specific signature sequence was
      derived, and the available sequences were analyzed for residues of potential
      functional significance. A fully conserved intramembranous histidyl residue,
      present within a putative amphipathic, alpha-helical, transmembrane spanning
      segment, was identified which may serve as a part of an intrachannel heavy metal
      ion binding site. The occurrence of a proposed extramembranal metal binding motif
      (H X H X H) was examined in order to evaluate its potential functional
      significance for various members of the family. The computational analyses
      reported in this topical review should serve as a guide to future researchers
      interested in the structure-function relationships of ZIP family proteins.

PMID- 9784583
TI  - Transcellular chloride pathways in ambystoma proximal tubule.
AB  - The transport mechanisms of Ambystoma proximal tubule that mediate transcellular
      Cl- absorption linked to Na+ were investigated in isolated perfused tubules using
      Cl--selective and voltage-recording microelectrodes. In control solutions
      intracellular activity of Cl- (aiCl) is 11.3 +/- 0.5 mm, the basolateral (V1),
      apical (V2), and transepithelial (V3) potential differences are -68 +/- 1.2 mV,
      +62 +/- 1.2 mV and -6.4 +/- 0.3 mV, respectively. When Na+ absorption is
      decreased by removal of organic substrates from the lumen, aiCl falls by 1.3 +/-
      0.3 mm and V2 hyperpolarizes by +11.4 +/- 1.7 mV. Subsequent removal of Na+ from
      the lumen causes aiCl to fall further by 2.3 +/- 0.4 mm and V2 to hyperpolarize
      further by +15.3 +/- 2.4 mV. The contribution of transporters and channels to the
      observed changes of aiCl was examined using ion substitutions and inhibitors.
      Apical Na/Cl or Na/K/2Cl symport is excluded because bumetanide, furosemide or
      hydrochlorothiazide have no effect on aiCl. The effects of luminal HCO-3 removal
      and/or of disulfonic stilbenes argue against the presence of apical Cl-base
      exchange such as Cl-HCO3 or Cl-OH. The effects of basolateral HCO-3 removal, of
      basolateral Na+ removal and/or of disulfonic stilbenes are compatible with
      presence of basolateral Na-independent Cl-base exchange and Na-driven Cl-HCO3
      exchange. Several lines of evidence favor conductive Cl- transport across both
      the apical and basolateral membrane. Addition of the chloride-channel blocker
      diphenylamine-2-carboxylate to the lumen or bath, increases the aiCl by 2.4 +/-
      0.6 mm or 2.9 +/- 1.0 mm respectively. Moreover, following inhibition by DIDS of
      all anion exchangers in HCO-3-free Ringer, the equilibrium potential for Cl- does
      not differ from the membrane potential V2. Finally, the logarithmic changes in
      aiCl in various experimental conditions correlate well with the simultaneous
      changes in either basolateral or apical membrane potential. These findings
      strongly support the presence of Cl- channels at the apical and basolateral cell
      membranes of the proximal tubule.

PMID- 9784580
TI  - A globally disseminated M1 subclone of group A streptococci differs from other
      subclones by 70 kilobases of prophage DNA and capacity for high-frequency
      intracellular invasion.
AB  - The M1inv+ subclone of M1 group A streptococci that spread globally in the late
      1980s and early 1990s was previously identified by restriction fragment length
      polymorphism (RFLP), M protein, and SpeA exotoxin sequence analyses. Strains
      representing this subclone were characterized with regard to carriage of
      bacteriophage and capacity to invade cultured human epithelial cells. The M1inv+
      subclone was found to harbor two entirely different prophages, phage T13 and
      phage T14, which together supplement its genome with nearly 70 kb of DNA. Phage
      T14 encodes the SpeA exotoxin and is closely related to the classic converting
      phage T12. Plaque-forming characteristics and RFLP analyses of phages T13 and T14
      were compared to each other and to phage T12. Other subclones of M1, isolated in
      the 1970s to the early 1980s, lacked both prophages. The M1inv+ subclone was
      previously reported to be efficiently internalized by human epithelial cells.
      This potential was confirmed and expanded by comparing a variety of clinical
      isolates. The capacity for high-frequency invasion of epithelial cells was not
      transmitted to a laboratory strain of group A streptococci by the above-mentioned
      bacteriophages.

PMID- 9784584
TI  - Membrane fusion and rupture in liposomes: effect of biodegradable pH-sensitive
      surfactants.
AB  - Biodegradable pH-sensitive surfactants (BPS) are a unique family of easily
      metabolized compounds that demonstrate pH-dependent surface activity. These
      agents, in combination with other delivery systems, have demonstrated effects in
      enhancing transnucleic acid activity. The increased activity has been
      hypothesized to occur from a release of endosomal contents. Simply, the BPS
      delivery system containing nucleic acids enters the cell through an endocytotoic
      process. It encounters an acidic pH and becomes surface active leading to defects
      in the endosomal membrane. In the current study, an in vitro model membrane was
      used to better understand the liposome defect mechanisms that BPS elicit. Using
      this system, it is shown that BPS can induce both liposome fusion and rupture
      depending upon the pH and mole ratio of BPS to membrane lipids. Futhermore,
      liposome fusion induced by BPS was dependent on the total numbers of liposome
      particles while rupture was independent of interacting liposome particles. The
      generated data indicate that BPS agents act differently from other typical
      surface active agents and fuosgenic compounds. Instead of facilitating membrane
      fusion through the hexagonal II phase, BPS appeared to contribute and participate
      in the membrane fusion at different stages.

PMID- 9784585
TI  - Electrocoupling of ion transporters in plants: interaction with internal ion
      concentrations.
AB  - There are five major electroenzymes in the plasmalemma of plant cells: a driving
      electrogenic pump, inward and outward rectifying K+ channels, a Cl--2H+
      symporter, and Cl--channels. It has been demonstrated previously (Gradmann, Blatt
      & Thiel 1993, J. Membrane Biol. 136:327-332) how voltage-gating of these
      electroenzymes causes oscillations of the transmembrane voltage (V) at constant
      substrate concentrations. The purpose of this study is to examine the interaction
      of the same transporter ensemble with cytoplasmic concentrations of K+ and Cl-.
      The former model system has been extended to account for changing internal
      concentrations. Constant-field theory has been applied to describe the influence
      of ion concentrations on current-voltage relationships of the active channels.
      The extended model is investigated using a reference set of model parameters. In
      this configuration, the system converges to stable slow oscillations with
      intrinsic changes in cytoplasmic K+ and Cl- concentrations. These slow
      oscillations reflect alternation between a state of salt uptake at steady
      negative values of V and a state of net salt loss at rapidly oscillating V, the
      latter being analogous to the previously reported oscillations. By switching off
      either concentration changes or gating, it is demonstrated that the fast
      oscillations are mostly due to the gating properties of the Cl- channel, whereas
      the slow oscillations are controlled by the effect of the Cl- concentration on
      the current. The sensitivity of output results y (e.g., frequency of
      oscillations) to changes of the model parameters x (e.g., maximum Cl-
      conductance) has been investigated for the reference system. Further examples are
      presented where some larger changes of specific model parameters cause
      fundamentally different behavior, e.g., convergence towards a stable state of
      only the fast oscillations without intrinsic concentration changes, or to a
      steady-state without any oscillations. The main and general result of this study
      is that the osmotic status of a plant cell is stabilized by the ensemble of
      familiar electroenzymes through oscillatory interactions with the internal
      concentrations of the most abundant ions. This convergent behavior of the stand
      alone system is an important prerequisite for osmotic regulation by means of
      other physiological mechanisms, like second messengers and gating modifiers.

PMID- 9784586
TI  - Phenotypic adaptation of tonoplast fluidity to growth temperature in the CAM
      plant Kalanchoe daigremontiana ham. et Per. is accompanied by changes in the
      membrane phospholipid and protein composition.
AB  - The present study deals with the phenotypic adaptation of tonoplast fluidity in
      the CAM plant Kalanchoe daigremontiana to changes in growth temperature.
      Tonoplast fluidity was characterized by measuring fluorescence depolarization in
      membranes labeled with fluorescent fatty acid analogues and by following
      formation of eximeres in membranes labeled by eximere-forming fluorophores. With
      both techniques it was found that exposure of the plants to higher growth
      temperature compared with the control decreased the fluidity of the tonoplast
      while exposure to lower growth temperature caused the opposite. Three hours of
      high temperature treatment (raised from 25 degreesC to 35 degreesC; "heat shock")
      were sufficient to decrease the tonoplast fluidity to roughly the same extent as
      growth under high temperature for 30 days. The phenotypic response of tonoplast
      fluidity to changes in growth temperature was found only in the complete
      membrane, not however in the lipid matrix deprived of the membrane proteins. Heat
      treatments of the plants decreased the lipid/protein ratio while exposure to low
      temperature (for 30 days) increased it. Heat treatments led to a decrease in the
      percentage of linolenic acid (C18:3) and linoleic acid (C18:2), heat shock and
      low temperature treatments induced an increase in the percentage of linoleic acid
      (C18:3), with concomitant decrease in the percentage of linoleic acid (C18:2).
      However, in the case of heat shock, increase in linolenic acid concerned mainly
      monogalactosyldiacylglycerol, while with low temperature treatment linoleic acid
      increased in phosphatidylcholine. Both treatment of the plants with high and low
      temperature led to a slight decrease in the contribution of phosphatidylcholine
      and phosphoethanolamine to the total phospholipid content of the tonoplast. High
      temperature treatment of the plants not only decreased the phospholipid/protein
      ratio in the tonoplast, but also led to the occurrence of a 35 kDa polypeptide in
      the tonoplast which cross-reacted with an antiserum against the tonoplast H+
      ATPase holoenzyme. The important role of membrane proteins in bringing about the
      phenotypic rigidization of the tonoplast was mimicked by reconstitution
      experiments showing that incorporation of the proteins isolated from the
      tonoplast into phosphatidylcholine vesicles decreased the fluidity of this
      membrane system. As to be expected from the analyses in the natural membrane, the
      degree of this effect depended on the phospholipid/protein ratio.

PMID- 9784589
TI  - Chlamydomonas genetics, a tool for the study of bioenergetic pathways.

PMID- 9784587
TI  - The P-glycoprotein efflux pump: how does it transport drugs?

PMID- 9784591
TI  - Molecular mechanisms of cholestasis: causes and consequences of impaired bile
      formation.

PMID- 9784590
TI  - Dopamine agonist treatment ameliorates hyperglycemia, hyperlipidemia, and the
      elevated basal insulin release from islets of ob/ob mice.
AB  - One of the characteristics of obesity-associated diabetes is an elevated fasting
      plasma insulin concentration with a weak insulin secretory response to subsequent
      glucose stimulation. Evidence suggests that hyperglycemia and hyperlipidemia may
      contribute to the initiation and progression of this disordered islet glucose
      sensing. It has been proposed that reducing hyperglycemia and hyperlipidemia per
      se may improve islet glucose sensing. Here we studied glucose-dependent insulin
      release in islets isolated from ob/ob mice treated with dopamine agonists
      (bromocriptine and SKF38393, BC/SKF) which significantly reduced circulating
      glucose and lipid levels of ob/ob mice. Islets from BC/SKF-treated mice showed a
      marked decrease of the elevated basal insulin release to levels similar to lean
      mice. Such treatment also induced a higher secretory response to glucose
      stimulation compared with that in ob/ob mice with sustained hyperglycemia and
      hyperlipidemia. Similarly, when islets from untreated ob/ob mice were cultured
      for 7 days in 11 mM glucose in the absence of free fatty acid, the basal insulin
      release was significantly decreased and high glucose stimulated insulin release
      increased compared with that from islets cultured in medium containing 30 mM
      glucose and 2 mM oleate. The BC/SKF-induced reduction of elevated basal insulin
      release was associated with decreased hexokinase activity and basal cyclic AMP
      content in islet tissue. Our results demonstrate that dopamine agonist treatment
      improves basal insulin release in ob/ob mice and this effect may be mediated, in
      part, by a reduction of hyperglycemia and hyperlipidemia.

PMID- 9784592
TI  - TCF-4 binds beta-catenin and is expressed in distinct regions of the embryonic
      brain and limbs.
AB  - The Tcf family of transcription factors, in association with beta-catenin,
      mediate Wnt signaling by transactivating downstream target genes. Given the
      function of wnt genes in neural development and organogenesis, Tcf transcription
      factors must be integral to the development of many embryonic tissues. In fact,
      the role of Tcf genes in axis formation in Xenopus and in segment polarity in
      Drosophila is well established. In this report, we have identified two isoforms
      of the mouse Tcf-4 gene. Tcf-4 expressing cells showed nuclear localization of
      beta-catenin. Although Tcf-4 RNA was widely distributed throughout embryogenesis,
      high levels of Tcf-4 expression were particularly evident in the developing CNS
      and limb buds. In extended streak stage embryos (E7.5), Tcf4 expression was
      detected in anterior endoderm. E8.5 embryos had Tcf-4 expression in rostral
      neural plate and in alternating rhombomeres of the hindbrain. By E9.5 and
      thereafter, expression in the hindbrain disappeared and strong expression was
      detected in the diencephalon. Strikingly Tcf-4 expression in the forebrain was
      undetected in Small eye mutant embryos indicating that Pax-6 is required for Tcf
      4 expression in the forebrain. In developing limbs, Tcf-4 is readily detected
      starting at E10.5 and is limited to mesenchymal cells surrounding the areas of
      chondrification. These data indicate a function for Tcf-4 in neural and limb
      development, two tissues where Wnt signaling plays an essential role.

PMID- 9784593
TI  - Differential regulation of MMP-13 (collagenase-3) and MMP-3 (stromelysin-1) in
      mouse calvariae.
AB  - Bone resorption in mice involves the degradation of extracellular matrix. Whereas
      several proteases seem to be implicated in this process, it becomes increasingly
      clear that matrix metalloproteinases (MMPs), amongst them especially MMP-13 and
      MMP-3, play an essential role. We have purified MMP-13 and MMP-3 from mouse
      calvariae-conditioned media by differential fractionation and analyzed their
      collagenolytic, caseinolytic, gelatinolytic and proteoglycanolytic activities. It
      could be shown that in mouse calvariae-conditioned media most of the measured
      enzyme activities were due to MMP-13, although zymographies revealed that MMP-3,
      MMP-2, MMP-9 as well as TIMPs were present too. MMP-13 and MMP-3 proteins were
      detected and their enzyme activities were neutralized by specific polyclonal
      antisera. Furthermore, it was demonstrated that in cultures of mouse calvariae
      the production of MMP-13 was induced by the potent MMP-stimulator heparin and by
      parathyroid hormone (PTH), whereas the levels of MMP-3 remained unchanged.
      Although PTH-induced bone resorption was inhibited by calcitonin treatment, MMP
      13 mRNA and protein expression were not significantly altered by this hormone.
      Together with previous observations, these results indicate that PTH regulates
      bone resorption through MMP-13, but not by MMP-3, and that its reversion by
      calcitonin involves neither of the two enzymes.

PMID- 9784594
TI  - A novel stop codon mutation (X417L) of the ferrochelatase gene in bovine
      protoporphyria, a natural animal model of the human disease.
AB  - Protoporphyria (PP) is caused by a deficiency of ferrochelatase (FC) activity,
      which catalyzes the final step in the heme biosynthesis pathway. Bovine are the
      only species other than man with naturally occurring PP. For expression of the PP
      phenotype, two copies of the mutated gene are necessary in bovine, whereas one
      copy is sufficient in humans. We report the first potential disease-causing
      mutation in the bovine FC gene. The coding region of FC was sequenced from the
      liver tissue of protoporphyric and normal bovine. A transversion was identified
      at nucleotide position 1250 which changed the stop codon to leucine (TGA-->TTA)
      in the protoporphyric FC sequence. As a consequence, the mutant protein is
      predicted to have an additional 27 amino acids. To screen other bovine for the G-
      >T transversion, cDNAs from liver tissue of clinically and biochemically normal,
      and from heterozygous and homozygous affected animals were used for allele
      specific polymerase chain reaction. Three normal animals had only the G allele,
      five affected animals had only the T allele, and three heterozygous animals had
      both the G and T alleles. These results support our hypothesis that this mutation
      causes PP in bovine.

PMID- 9784595
TI  - Spatio-temporal expression of FGFR 1, 2 and 3 genes during human embryo-fetal
      ossification.
AB  - Mutations in FGFR 1-3 genes account for various human craniosynostosis syndromes,
      while dwarfism syndromes have been ascribed exclusively to FGFR 3 mutations.
      However, the exact role of FGFR 1-3 genes in human skeletal development is not
      understood. Here we describe the expression pattern of FGFR 1-3 genes during
      human embryonic and fetal endochondral and membranous ossification. In the limb
      bud, FGFR 1 and FGFR 2 are initially expressed in the mesenchyme and in epidermal
      cells, respectively, but FGFR 3 is undetectable. At later stages, FGFR 2 appears
      as the first marker of prechondrogenic condensations. In the growing long bones,
      FGFR 1 and FGFR 2 transcripts are restricted to the perichondrium and periosteum,
      while FGFR 3 is mainly expressed in mature chondrocytes of the cartilage growth
      plate. Marked FGFR 2 expression is also observed in the periarticular cartilage.
      Finally, membranous ossification of the skull vault is characterized by co
      expression of the FGFR 1-3 genes in preosteoblasts and osteoblasts. In summary,
      the simultaneous expression of FGFR 1-3 genes in cranial sutures might explain
      their involvement in craniosynostosis syndromes, whereas the specific expression
      of FGFR 3 in chondrocytes does correlate with the involvement of FGFR 3 mutations
      in inherited defective growth of human long bones.

PMID- 9784596
TI  - Molecular cloning and characterization of a cDNA encoding canine type VII
      collagen non-collagenous (NC1) domain, the target antigen of autoimmune disease
      epidermolysis bullosa acquisita (EBA).
AB  - Type VII collagen, the major component of anchoring fibrils, serves as tight
      adhesion of skin basement membrane zone (BMZ) through its amino-terminal non
      collagenous (NC1) domain. The NC1 domain is targeted by autoantibodies of an
      acquired blistering skin disease termed epidermolysis bullosa acquisita (EBA)
      naturally occurring in humans and dogs. We cloned the full-length canine type VII
      collagen NC1 domain cDNA and delineated its molecular and immunological
      characteristics. The canine NC1 domain cDNA consists of 3759 nucleotides encoding
      for 1253 amino acids, with a molecular mass of approx. 134 kDa and a 17 amino
      acid signal peptide. The expression of canine type VII collagen was confirmed by
      Northern blot analysis and by a rabbit antibody raised against a 17 amino acid
      peptide deduced from canine NC1 sequence. Comparison of canine NC1 with the
      corresponding human sequence indicated 86.7% and 87.6% identity at the nucleotide
      and deduced amino acid levels respectively. The protein homology reached greater
      than 95% within two immunodominant epitope areas. Furthermore, human EBA
      autoantibodies and a rabbit anti-human NC1 cross-reacted with canine skin BMZ and
      the newly synthesized canine type VII collagen. The molecular and immunological
      identities between human and canine NC1 domains suggest that NC1 may be critical
      for the EBA development.

PMID- 9784597
TI  - Upregulation of endothelin-1 production by lysophosphatidic acid in rat aortic
      endothelial cells.
AB  - Addition of lysophosphatidic acid (LPA) to rat aorta-derived endothelial cells
      significantly induced preproendothelin-1 (preproET-1) mRNA expression. PreproET-1
      mRNA levels reached a plateau within 1 h after the addition of 0.5 microM LPA and
      declined after 2 h. The induction was superinduced by cycloheximide and was
      blocked by actinomycin D. Suramin, an LPA receptor antagonist, abolished the
      induction of preproET-1 mRNA by LPA. Protein kinase C inhibitors, H7 and
      bisindolylmaleimide, were able to block the induction. Transient transfection
      experiment revealed that the elevated preproET-1 mRNA was a result of the
      activation of ET-1 gene activity. Electrophoretic mobility shift assay revealed
      that LPA stimulated the binding of AP-1. The secreted level of ET-1 was elevated
      2.3-fold after 12 h of stimulation with LPA. Our results suggest that the
      upregulation of preproET-1 by LPA may serve to augment and prolong the
      vasoconstriction action of LPA.

PMID- 9784598
TI  - Characterization of the zebrafish Orb/CPEB-related RNA binding protein and
      localization of maternal components in the zebrafish oocyte.
AB  - The animal/vegetal axis of the zebrafish egg is established during oogenesis, but
      the molecular factors responsible for its specification are unknown. As a first
      step towards the identification of such factors, we present here the first
      demonstration of asymmetrically distributed maternal mRNAs in the zebrafish
      oocyte. To date, we have distinguished three classes of mRNAs, characterized by
      the stage of oocyte maturation at which they concentrate to the future animal
      pole. We have further characterized one of these mRNAs, zorba, which encodes a
      homologue of the Drosophila Orb and Xenopus CPEB RNA-binding proteins. Zorba
      belongs to the group of earliest mRNAs to localize at the animal pole, where it
      becomes restricted to a tight subcortical crescent at stage III of oogenesis. We
      show that this localization is independent of microtubules and microfilaments,
      and that the distribution of Zorba protein parallels that of its mRNA.

PMID- 9784599
TI  - Pregnancy alters the in vitro responsiveness of the rabbit medial collateral
      ligament to neuropeptides: effect on mRNA levels for growth factors, cytokines,
      iNOS, COX-2, metalloproteinases and TIMPs.
AB  - Explants of tissue derived from the medial collateral ligament (MCL) of normal
      and pregnant NZW rabbits cultured in the presence of substance P (SP), calcitonin
      gene-related peptide (CGRP), or both neuropeptides were found to have altered
      mRNA levels for a number of relevant molecules. Using a very efficient RNA
      isolation method, semi-quantitative RT-PCR and rabbit-specific primers, mRNA for
      growth factors (TGFbeta, bFGF, IGF-2, ET-1), cytokines (IL-1, TNF), enzymes (COX
      2, iNOS), metalloproteinases (collagenase, stromelysin) and metalloproteinase
      inhibitors (TIMP-1, TIMP-2) were assessed after culture with or without
      neuropeptide. The results indicate that SP was effective in lowering mRNA levels
      for all of the molecules assessed in RNA from normal ligaments except IL-1beta,
      IGF-2 and TIMP-1, for which there was no significant effect. Similarly, CGRP was
      effective in lowering mRNA levels for all molecules except TNF, ET-1 and the
      TIMPs. The extent of the lowering of mRNA levels was both molecule-specific and
      neuropeptide-specific. When the experiments were repeated with ligament tissue
      from pregnant animals, a very different pattern of responsiveness to the
      neuropeptides was observed. While mRNA levels for 9/12 genes assessed were
      significantly affected by SP when normal MCL tissue was investigated, pregnancy
      abolished all significant responsiveness to this neuropeptide except for iNOS
      mRNA levels. In the case of iNOS mRNA, SP induced an increase in the steady-state
      levels, the opposite to what was observed with tissue from non-pregnant animals.
      For CGRP and SP+CGRP, tissue from pregnant animals was still responsive, but the
      pattern of responsiveness was changed from strictly a lowering of steady-state
      mRNA levels to elevations in mRNA levels for a number of genes. These findings
      indicate that mRNA levels for a number of genes can be influenced by
      neuropeptides known to be in ligaments. Thus, neuropeptides likely are important
      regulators of ligament cell metabolism. As the responsiveness to SP was nearly
      completely abolished during pregnancy, neuroregulatory influences mediated by
      this peptide are altered in the pregnant female. This loss of responsiveness to
      SP may also be one aspect of the analgesia associated with pregnancy.

PMID- 9784601
TI  - Effects of ethanol on the expression and secretion of bile salt-dependent lipase
      by pancreatic AR4-2J cells.
AB  - The mechanisms by which ethanol administration alters pancreatic function are
      unknown. We have evaluated the effects of chronic ethanol treatment on secretion
      of a digestive enzyme: the bile salt-dependent lipase (BSDL), by the rat
      pancreatic cell line AR4-2J (as a model). We report that ethanol (50-300 mM) in
      culture medium induced a rise, in secreted and intracellular BSDL, that was a
      function of the duration of treatment and of the ethanol concentration. This
      effect was not abolished by pyrazole, which suggests a direct effect of ethanol.
      We have further established that the increase of BSDL activity was due to an
      enhanced biosynthesis of the enzyme consecutive to a major steady-state level of
      mRNA encoding BSDL. Also, the subcellular localization showed a specific
      accumulation of BSDL in the cytosolic fraction of cells chronically treated with
      ethanol. Given the enzymatic properties of BSDL, all these data could have some
      physiological consequences regarding the digestive function, plasma lipid
      metabolism and intracellular cholesterol homeostasis.

PMID- 9784600
TI  - Identification and expression of two novel CLIP-170/Restin isoforms expressed
      predominantly in muscle.
AB  - CLIP-170 and Restin, microtubule-binding proteins originally cloned from human
      cells, are identical except for a stretch of 35 amino acids present in Restin,
      but missing from CLIP-170. Here we present the discovery of two novel isoforms of
      the CLIP-170/Restin gene in both chickens and humans. One of the new isoforms,
      named CLIP-170(11), contains an 11 amino acid insert instead of the 35 amino acid
      insert found in Restin. Eight of these 11 amino acids, including a helix-breaking
      proline residue, are perfectly conserved between chickens and humans. The second
      new isoform, named CLIP-170(11+35), contains both the 11 and 35 amino acid
      inserts in tandem. PCR analysis of chicken genomic DNA revealed that all four
      isoforms result from differential splicing of two exons in a region of the CLIP
      170 gene that contains approximately 8.6 kb of intervening sequence. We found
      that the CLIP-170(11) and CLIP-170(11+35) are expressed preferentially in muscle
      tissues. Chicken and human skeletal muscle express predominantly CLIP-170(11) and
      to a lesser extent CLIP-170 and CLIP-170(11+35). Adult chicken cardiac and smooth
      muscles also express CLIP-170(11) and CLIP-170(11+35), but CLIP-170 is the
      predominant isoform in these muscles as it is in all other tissues except brain.
      The ratios of CLIP-170 isoform expression found in embryonic and adult chicken
      cardiac muscles reveal that isoform expression is regulated differentially in
      different developmental stages as well as in different tissues.

PMID- 9784602
TI  - Calcium additional to that bound to the transport sites is required for full
      activation of the sarcoplasmic reticulum Ca-ATPase from skeletal muscle.
AB  - The sarcoplasmic reticulum Ca-ATPase is fully activated when approximately 1
      microM [Ca2+] saturates the two transport sites; higher [Ca] inhibits the ATPase
      by competition of Ca-ATP with Mg-ATP as substrates. Here we describe a novel
      effect of EGTA and other chelators, raising the possibility of an additional
      activating effect of Ca in the sub- or low microM range. Sarcoplasmic reticulum
      membranes were isolated from rabbit skeletal muscles. The ATPase activity was
      measured after incubation at 37 degreesC in 3 mM ATP, 3 mM MgCl2, 50 mM MOPS-Tris
      (pH 7.2), 100 mM KCl, and variable CaCl2, EGTA and calcimycin. In the absence of
      added EGTA and Ca the ATPase activity is high due to contaminant Ca. The
      determination of the ATPase activity in the presence of increasing amounts of
      EGTA, without added Ca, yields a decreasing sigmoidal function. Ki ranged between
      20 and 100 microM, depending on the enzyme concentration. Pi production is linear
      with time for several [EGTA] yielding suboptimal ATPase activities, which are
      inhibited by thapsigargin. These suboptimal Ca-ATPase activities are inhibited by
      preincubation of the enzyme in EGTA, at pH 7.2. This effect increases upon
      increasing EGTA concentration and preincubation time. The inhibitory effect of
      the previous exposure of the enzyme to EGTA is partially but significantly
      reverted by increasing [Ca2+] during incubations. Calcimycin and EDTA have
      similar effects as EGTA when added in preincubations. The effect of calcimycin is
      fully reverted by optimal [Ca2+] in incubations. The effects of EGTA, EDTA and
      calcimycin in preincubation are not additive. The results suggest that an
      additional calcium, lost during preincubations from a site with affinity near 1
      microM, is necessary for full activation of the ATPase.

PMID- 9784603
TI  - Analysis of Hoxa7/Hoxb7 mutants suggests periodicity in the generation of the
      different sets of vertebrae.
AB  - Mice were generated with targeted disruptions in Hoxa7 and Hoxb7, respectively.
      Mice carrying the Hoxa7 mutation are healthy. No abnormalities in the formation
      of the skeleton or other tissues were found in these mutants. Twelve percent of
      Hoxb7-/- mutants show first and second rib defects similar to those observed in
      mice homozygous for a Hoxb9 mutation (Chen, F., Capecchi, M.R., 1997. Dev. Biol.
      181, 186-196). Hoxb7-/- mice are also fertile and were used to generate double
      mutants with Hoxa7 to reveal potential interactions between these two paralogous
      genes. Mice homozygous for both mutations have first and second rib defects with
      higher penetrance and increased expressivity, indicating a functional role for
      Hoxa7 in the patterning of the upper thoracic region. Although Hoxb6, Hoxa7,
      Hoxb7, and Hoxb9 have distinctive anterior expression limits in axial mesoderm,
      the disruptions of these genes all yield first and second rib defects. A
      hypothesis is suggested to explain the observation that axial defects in these
      and other mouse Hox mutants appear to concentrate along the axial column at zones
      of transition between vertebral types.

PMID- 9784604
TI  - Inhibition of PMN- and HOC1-induced vascular injury in isolated rabbit lungs by
      acetylsalicylic acid: a possible link between neutrophil-derived oxidative stress
      and eicosanoid metabolism?
AB  - Neutrophils are involved in the pathogenesis of acute lung injury. The neutrophil
      derived enzyme myeloperoxidase (MPO) catalyzes the formation of the oxidant
      hypochlorous acid (HOCl). This study characterizes the effects of (A) continuous
      HOCl infusion, and (B) stimulated neutrophils on pulmonary circulation in an
      isolated rabbit lung model. Furthermore, the effect of cyclooxygenase inhibition
      by acetylsalicylic acid (ASA, 0.5 mM) on these effects was investigated. (A)
      Infusion of HOCl (in nmol min-1, groups: 0, 0+ASA, 1000, 1000+ASA, 2000, and
      2000+ASA) into the isolated organ was started after a 45-min steady-state period
      (t=0). (B) Neutrophils (PMN group: 1480+/-323 and ASA group 1294+/-320 microliter
      1) were added into the perfusate between (t=-45 min) and stimulated with FMLP (1
      microM) after two 45-min steady-state periods (t=0). Perfusate MPO activity was
      measured at t=-90, -45, 0, 1, 2, 3, 5, 10, 15, 30, 60, and 90 min. For both
      groups, pulmonary artery pressure (PAP) and lung weight were continuously
      recorded and the capillary filtration coefficient (Kf,c in 10(-4) cm(3) s(-1) cm
      H2O(-1) g(-1) was calculated from the slope of weight gain after a hydrostatic
      challenge at t=-45, -15, 30, 60 and 90 min. (A) Continuous HOCl infusion
      (1000/2000 nmol min-1) evoked a significant increase in DeltaPAP and an up to 10
      fold increase in Kf,c reaching the maximum extent of the observed effects
      significant earlier in the 2000 nmol min-1 group. ASA reduced DeltaPAPmax
      significantly to about 50% in corresponding groups and the increase in PAP and
      Kf,c occurred later in the ASA groups. (B) Neutrophil stimulation (PMN group/ASA
      group) evoked a rapid increase in DeltaPAP and MPO activity, while the changes in
      vascular permeability were rather moderate, but still significant. The release of
      MPO activity was similar in both groups. ASA significantly reduced the increase
      in DeltaPAP without affecting the release of MPO activity. Compared to baseline
      values, the preventive effects on vascular permeability increase reached level of
      significance as well. In summary, the described changes in pulmonary circulation
      caused by HOCl infusion or by neutrophil stimulation are significantly reduced by
      ASA. An involvement of cyclooxygenase products in the mediation of neutrophil
      derived oxidative stress could be concluded.

PMID- 9784605
TI  - Studies on the endothelin-1-induced contraction of rat granulation tissue pouch
      mediated by myofibroblasts.
AB  - A granulation tissue pouch, mostly composed of myofibroblasts, was prepared by
      injecting rats subcutaneously with croton oil. The contraction of the granulation
      tissue pouch caused by endothelin-1 (ET-1) and the effects of the ET receptor
      antagonists, BQ123 and BQ788 on it were thus examined. ET-1 produced contractions
      in a dose-dependent manner. Pretreatment with BQ123, an ETA receptor selective
      antagonist, shifted the dose-response curve to the right, whereas pretreatment
      with BQ788, an ETB receptor selective antagonist, showed little effect. IRL1620,
      an ETB receptor selective agonist, did not cause any contraction in the
      granulation tissue pouch. The existence of both ETA and ETB receptors in the
      granulation tissue pouch and in cultured myofibroblasts was demonstrated by RT
      PCR. Intracellular Ca2+ mobilization in Fura-2/acetyl-methoxy ester loaded
      cultured myofibroblasts isolated from the granulation tissue was also examined.
      ET-1 produced a transient increase in [Ca2+]i followed by a sustained elevation
      of [Ca2+]i, whereas IRL1620 caused only a transient peak. These results suggest
      that the ET-1 induced contraction of granulation tissue is mainly mediated
      through the mobilization of Ca2+ from the extracellular space caused by
      stimulation with ETA receptor.

PMID- 9784606
TI  - Developmental expression of the cell adhesion molecule-like protein tyrosine
      phosphatases LAR, RPTPdelta and RPTPsigma in the mouse.
AB  - Using RNA in situ hybridization we compared the expression patterns of the cell
      adhesion molecule-like receptor-type protein tyrosine phosphatases LAR, RPTP
      sigma and RPTP sigma during mouse development. We found that LAR is expressed in
      basal lamina-associated epithelial tissues of (neuro)ectodermal, neural
      crest/ectomesenchyme and endodermal origin. RPTP sigma is found in
      (neuro)ectodermal, neural crest-derived systems and in mesoderm-derived tissues.
      The expression pattern of RPTP sigma largely parallels that of RPTP sigma, in
      concordance with their proposed evolutionary history

PMID- 9784607
TI  - Cytochrome b559 of photosystem II.

PMID- 9784608
TI  - Function of zebrafish beta-catenin and TCF-3 in dorsoventral patterning.
AB  - We report the molecular cloning and expression of the zebrafish tcf-3 homologue
      and study its function and that of zebrafish betacat in dorsoventral patterning.
      Overexpression of mutant zTcf-3 products and Cadherin leads to a reduction in the
      expression of the dorsal-specific genes goosecoid and chording at the blastula
      stages, indicating a conserved role for betacat and tcf-3 in zebrafish dorsal
      axis induction. Later during gastrulation, overexpression of these same products
      leads to the ectopic expression of dorsal-specific genes in the marginal zone and
      the induction of ectopic axes, suggesting an additional role for betacat and Tcf
      3 at these later stages in the repression of dorsal fates.

PMID- 9784609
TI  - Lumbricin I, a novel proline-rich antimicrobial peptide from the earthworm:
      purification, cDNA cloning and molecular characterization.
AB  - A novel antimicrobial peptide was isolated and characterized from the earthworm,
      Lumbricus rubellus. The antimicrobial peptide was purified to homogeneity by a
      heparin-affinity column and C18 reverse-phase HPLC, and named lumbricin I.
      Lumbricin I was a proline-rich antimicrobial peptide of 62 amino acids (15%
      proline in molar ratio; molecular mass, 7231 Da), whose complete sequence was
      determined by a combination of peptide sequence and cDNA analysis. The peptide
      and cDNA sequence analysis revealed that lumbricin I was produced as a precursor
      form consisting of 76 amino acids, with 14 residues in a presegment and 62
      residues in mature lumbricin I. Lumbricin I showed antimicrobial activity in
      vitro against a broad spectrum of microorganisms without hemolytic activity. In
      addition, a 29-amino acid peptide, named lumbricin I(6-34), which was derived
      from residues 6-34 of lumbricin I, showed marginally stronger antimicrobial
      activity than lumbricin I. Northern blot analysis on total RNA revealed that
      expression of lumbricin I gene was not induced by bacterial infection, but was
      constitutively expressed. Furthermore, the expression of lumbricin I gene was
      specific in adult L. rubellus: Lumbricin I mRNA was detected only in adult L.
      rubellus, but not in eggs and young L. rubellus.

PMID- 9784610
TI  - The influence of elaborated pericellular matrix on the deformation of isolated
      articular chondrocytes cultured in agarose.
AB  - This study investigates the mechanical influence of pericellular matrix on the
      deformation of isolated articular chondrocytes compressed within 3% agarose
      specimens. After 1 day in culture, the cells were associated with minimal amounts
      of sulphated glycosaminoglycan (GAG) and hydroxyproline and exhibited substantial
      deformation from a spherical to an oblate ellipsoid morphology when subjected to
      20% gross compressive strain. However, over the 6 day culture period, there was a
      reduction in cell deformation associated with an increase in matrix content.
      Treatment with testicular hyaluronidase at days 3 and 6 reduced sulphated GAG
      content to levels observed in untreated specimens at day 1. At day 3, the
      resulting cell deformation during 20% compression was equivalent to that in
      specimens compressed at day 1. However, at day 6 cell deformation was only
      partially restored, suggesting the presence of additional structural matrix
      components, other than sulphated GAG, which were not present at day 3. Dual
      scanning confocal microscopy indicated that the elaborated matrix formed a
      pericellular shell which did not deform during compression and was therefore
      stiffer than the 3% agarose substrate. Therefore, the elaboration of a
      mechanically functional pericellular matrix within 6 days, effectively limits the
      potential involvement of cell deformation in mechanotransduction within cell
      seeded systems such as those employed for cartilage repair.

PMID- 9784612
TI  - Hydrolysis of hexose pentaacetate esters in rat pancreatic islets.
AB  - The pentaacetate esters of selected hexoses were recently found to stimulate
      insulin release. The kinetics of their hydrolysis was now investigated in both
      rat pancreatic islet homogenates and intact islets. In islet homogenates, the
      hydrolysis of alpha-d-glucose pentaacetate, as judged from the measurement of
      acetate production, displayed a pH optimum of 7.4 and a Km for the ester of 0.95
      mM. At pH 7.4, the reaction velocity was about 5 times higher than the rate of
      alpha-d-glucose pentaacetate hydrolysis by intact islets, as judged from the
      ester-induced increase in the acetate content of both the islet and surrounding
      incubation medium. Comparable results were obtained in intact islets exposed to
      either beta-l-glucose pentaacetate or beta-d-galactose pentaacetate. The ester
      content of the islets after 120 min incubation was close to 0.1 nmol/islet,
      yielding an apparent intracellular concentration at least one order of magnitude
      higher than the extracellular concentration (1.7 mM). These findings indicate
      that hexose esters that either stimulate insulin release or fail to do so are
      equally well taken up and hydrolyzed by islet cells. They are compatible,
      therefore, with the view that the insulinotropic action of some of these esters
      may be favored by the catabolism of their hexose moiety, although some other
      mechanisms for stimulation of insulin release must be operative in the case of
      beta-l-glucose pentaacetate.

PMID- 9784611
TI  - beta-TrCP is a negative regulator of Wnt/beta-catenin signaling pathway and
      dorsal axis formation in Xenopus embryos.
AB  - The Wnt/beta-catenin signaling pathway is responsible for the establishment of
      dorsoventral axis of Xenopus embryos. The recent finding of the F-box/WD40-repeat
      protein slimb in Drosophila, whose loss-of-function mutation causes ectopic
      activation of wingless signaling (Jiang, J., Struhl, G., 1998. Nature 391, 493
      496), led us to examine the role of its vertebrate homolog betaTrCp in the
      Wnt/beta-catenin signaling and dorsal axis formation in Xenopus embryos. Co
      injection of betaTrCp mRNA diminished Xwnt8 mRNA-induced axis formation and
      expression of Siamois and Xnr3, suggesting that betaTrCP is a negative regulator
      of the Wnt/beta-catenin signaling pathway. An mRNA for a betaTrCp mutant
      construct (DeltaF), which lacked the F-box domain, induced an ectopic axis and
      expression of Siamois and Xnr3. Because this activity of DeltaF was suppressed by
      co-injection of DeltaF TrCP mRNA, DeltaF likely acts in a dominant negative
      fashion. The activity of DeltaF was diminished by C-cadherin, glycogen synthase
      kinase 3 and Axin, but not by a dominant negative dishevelled. These results
      suggest that betaTrCp can act as a negative regulator of dorsal axis formation in
      Xenopus embryos.

PMID- 9784613
TI  - The two mature transcripts of the chick calcitonin gene are expressed within the
      central nervous system during embryogenesis.
AB  - Calcitonin mRNA and calcitonin gene-related peptide (CGRP) mRNA both are
      generated from the calcitonin gene because of tissue-specific alternative
      splicing of the primary transcript. It is currently established that, of the two
      mature transcripts, calcitonin mRNA is far the predominant transcript produced in
      thyroid C-cells whereas only CGRP mRNA is produced in the nervous system.
      However, here we provide evidence that the two splicing forms of the chick
      calcitonin primary transcript are found within the developing central nervous
      system, although displaying specific patterns of expression. While CGRP mRNA is
      first expressed in motor neurons at rather advanced stages of embryogenesis,
      calcitonin mRNA is expressed in the floor plate and dorsal rhombencephalon from
      earliest stages.

PMID- 9784614
TI  - Nucleation and elongation of actin filaments in the presence of high speed
      supernate from neutrophil lysates: modulating effects of Ca2+ and
      phosphatidylinositol-4,5-bisphosphate.
AB  - Cell motility depends on the rapid growth of cortical actin filaments whose
      barbed ends are capped in the resting cell. High speed supernates (HSS) of dilute
      neutrophil lysates contain actin monomers and/or oligomers that can be induced to
      polymerize by certain stimuli. We questioned whether some of the actin remaining
      in the supernate after high speed centrifugation exists as occult nucleation
      sites which can elongate when uncapped. Phosphatidylinositol-4,5-bisphosphate
      (PIP2) may play a critical role as an intracellular messenger in cytoskeletal
      rearrangement after stimulation by removing cappers from barbed filament ends.
      The experiments reported here examine the separate and interactive effects of
      PIP2 micelles and micromolar [Ca2+] on the rates of nucleation and elongation of
      pyrenyl-G-actin in the presence of HSS. HSS slowed the nucleation and elongation
      rates of gel-filtered pyrenyl-G-actin polymerized at submicromolar [Ca2+]. Under
      these conditions, PIP2 only slightly increased the number of nucleation sites,
      but delayed the slowing of the elongation rate in the presence of HSS. Nucleating
      activity in HSS could be induced by the addition of micromolar [Ca2+] and totally
      abolished by immunoprecipitation of gelsolin from HSS; incubation of HSS with
      PIP2 at micromolar [Ca2+] slightly decreased the number of calcium-induced
      nucleation sites in the supernate. Incubation of HSS with PIP2 before the
      addition of calcium led to a greater reduction in Ca2+-inducible nucleation
      sites. HSS possessed more nucleation sites after simultaneous exposure to PIP2
      and Ca2+, followed by chelation of Ca2+ with EGTA, than HSS preincubated at
      micromolar [Ca2+] without PIP2. At submicromolar [Ca2+], PIP2 only generated a
      few barbed end nucleation sites in the HSS, but lessened the gradual slowing of
      elongation seen with HSS in the absence of PIP2, presumably by preventing capping
      by capping protein-beta2 in the supernate. Pointed end nucleating sites in HSS,
      attributable to gelsolin, could be created by adding micromolar [Ca2+]. The
      preincubation of HSS with PIP2 in the absence of micromolar [Ca2+] decreased the
      number of Ca2+-inducible nucleation sites in the HSS. Under conditions mimicking
      the sequential rise and fall of cytosolic [Ca2+] after stimulation, PIP2
      accelerated actin polymerization despite the inhibitory action of HSS by
      maintaining Ca2+-activated nucleation sites. These observations suggest that a
      possible role for PIP2 in modulating cytoskeletal growth in vivo may be to
      regulate nucleation sites activated by sequential changes in cytosolic [Ca2+].

PMID- 9784615
TI  - Molecular cloning of Zcoe2, the zebrafish homolog of Xenopus Xcoe2 and mouse EBF
      2, and its expression during primary neurogenesis.
AB  - Xcoe2 is a recently identified HLH transcription factor of the Xenopus primary
      neurogenesis pathway, which is necessary downstream of Neurogenin to stabilize
      neuroblast determination (Dubois, L. et al., 1998. Curr. Biol. 8, 199-209). We
      report here the embryonic expression pattern of Zcoe2, its zebrafish homolog. As
      observed for Xcoe2, Zcoe2 is strongly expressed in a subset of the neurogenin1-
      (ngn1-) positive primary neuroblasts of the spinal cord. In the anterior neural
      plate, in contrast, Zcoe2 is expressed earlier and more widely than ngn1. This
      pattern is strongly maintained in the presumptive mesencephalon and rhombomeres 1
      4 until the 2-3-somite stage. This expression of Zcoe2 in the brain anlage calls
      for a re-analysis in zebrafish of the functional relationship demonstrated in
      Xenopus between Coe2 and Neurogenin factors. At later stages, Zcoe2 is expressed
      in early forming neurons of the anterior brain and is a marker of the olfactory
      placodes.

PMID- 9784616
TI  - Measurements of variable chlorophyll fluorescence using fast repetition rate
      techniques: defining methodology and experimental protocols 
AB  - We present a methodology, called fast repetition rate (FRR) fluorescence, that
      measures the functional absorption cross-section (sigmaPS II) of Photosystem II
      (PS II), energy transfer between PS II units (p), photochemical and
      nonphotochemical quenching of chlorophyll fluorescence, and the kinetics of
      electron transfer on the acceptor side of PS II. The FRR fluorescence technique
      applies a sequence of subsaturating excitation pulses ('flashlets') at
      microsecond intervals to induce fluorescence transients. This approach is
      extremely flexible and allows the generation of both single-turnover (ST) and
      multiple-turnover (MT) flashes. Using a combination of ST and MT flashes, we
      investigated the effect of excitation protocols on the measured fluorescence
      parameters. The maximum fluorescence yield induced by an ST flash applied shortly
      (10 &mgr;s to 5 ms) following an MT flash increased to a level comparable to that
      of an MT flash, while the functional absorption cross-section decreased by about
      40%. We interpret this phenomenon as evidence that an MT flash induces an
      increase in the fluorescence-rate constant, concomitant with a decrease in the
      photosynthetic-rate constant in PS II reaction centers. The simultaneous
      measurements of sigmaPS II, p, and the kinetics of Q-A reoxidation, which can be
      derived only from a combination of ST and MT flash fluorescence transients,
      permits robust characterization of the processes of photosynthetic energy
      conversion.

PMID- 9784617
TI  - Cholera toxin stimulates type II pneumocyte proliferation by a cyclic AMP
      independent mechanism.
AB  - Cholera toxin (CT) stimulated DNA synthesis by low-density primary cultures of
      adult rat type II pneumocytes (T2P) in a dose-dependent manner, either in the
      presence or the absence of serum. In the presence of 1% rat serum, 1 microgram/ml
      CT also stimulated a 50% increase in cell number over 8 days of incubation
      (P<0.01); this was in addition to a 2-fold increase in cell number induced by the
      serum alone (P<0.05). The same dose of CT also elevated intracellular cAMP and
      the total activity of protein kinase A (both P<0.01), suggesting toxin
      stimulation of T2P proliferation by a cAMP-dependent mechanism. However, the
      effect of CT on DNA synthesis could not be mimicked by 8-bromoadenosine 3':5'
      cyclic monophosphate (8-bromo-cAMP), nor by N6,2'-O-dibutyryladenosine 3':5'
      cyclic monophosphate (dibutyryl-cAMP), each tested over a wide range of
      concentrations. l-Isoproterenol stimulated surfactant secretion by over 5-fold
      (P<0. 01), but neither the beta-agonist, forskolin nor 3-isobutyl-1
      methylxanthine had any significant effect on DNA synthesis. The purified B
      subunit of CT stimulated DNA synthesis to the same degree as did the holotoxin,
      either in the presence or the absence of rat serum. In contrast, the purified A
      subunit had no significant effect. These data suggest that cholera toxin
      stimulates type II pneumocyte proliferation through a mechanism that is
      independent of cAMP, protein kinase A and toxin-catalyzed ADP-ribosylation.

PMID- 9784618
TI  - Factors determining electron-transfer rates in cytochrome c oxidase:
      investigation of the oxygen reaction in the R. sphaeroides enzyme.
AB  - We have investigated the kinetics of the single-turnover reaction of fully
      reduced solubilised cytochrome c oxidase (cytochrome aa3) from Rhodobacter
      sphaeroides with dioxygen using the flow-flash methodology and compared the
      results to those obtained with the well-characterised bovine mitochondrial
      enzyme. The overall reaction sequence was the same in the two enzymes, but the
      extents and rates of the electron-transfer reactions differed, implying
      differences in redox potentials, and/or interaction energies between electrons
      and protons during oxygen reduction. As with the bovine enzyme, the R.
      sphaeroides enzyme displayed two major kinetic phases of proton uptake with rate
      constants of approximately 5000 s-1 and approximately 500 s-1 at pH 7.9,
      concomitant with the peroxy to oxoferryl and oxoferryl to oxidised states. The
      net number of protons taken up in the R. sphaeroides enzyme was about
      approximately 1.9, which implies that upon reduction, the enzyme has to pick up
      approximately 2.1 H+ from the medium. On the basis of the comparison of electron
      transfer reactions in the two enzymes, we conclude that the transfer rate of the
      fourth electron to the binuclear centre is not only determined by the electron
      transfer rate from haem a to the binuclear centre, but also by the electron
      equilibrium between CuA and haem a. In addition, in contrast to the bovine
      enzyme, where the electron- and proton-transfer rates during oxidation of the
      fully reduced enzyme by O2 are all faster than the overall turnover rate, in the
      R. sphaeroides enzyme, the slowest kinetic phase was rate limiting for the
      overall turnover. Moreover, the comparison of the reactions in the two systems
      shows that in the R. sphaeroides enzyme, the electrons are more evenly
      distributed among the redox centres during oxygen reduction. This enables
      investigations of effects also of minor perturbations on, e.g., the electron
      transfer characteristics in mutant enzymes, for which this study forms the basis.

PMID- 9784619
TI  - Protein tyrosine phosphorylation in signalling pathways leading to the activation
      of gelatinase A: activation of gelatinase A by treatment with the protein
      tyrosine phosphatase inhibitor sodium orthovanadate.
AB  - Fibroblasts in monolayer culture secrete gelatinase A (MMP2; 72 kDa type IV
      collagenase) only in its proenzyme form. Unlike other secreted matrix
      metalloproteinases, progelatinase A is refractory to activation by serine
      proteinases. Disparate agents, including monensin, cytochalasin D, and
      concanavalin A, have been found to mediate the activation of gelatinase A zymogen
      secreted by fibroblast monolayers. Our finding that monensin-mediated activation
      can be reversed by the protein tyrosine kinase inhibitor genistein (Li et al.,
      Experimental Cell Research 232 (1997) 332) prompted us to investigate the effect
      of the specific inhibitor of protein tyrosine phosphatases, sodium orthovanadate,
      on progelatinase A activation. Treatment of fibroblast monolayers with
      orthovanadate also results in the secretion of activated gelatinase A. This
      activation is dose- and time-dependent, requires protein synthesis, and is
      associated with cell membranes. Vanadate-mediated activation does not occur in
      the presence of herbimycin A, a protein tyrosine kinase inhibitor. As with
      progelatinase activation mediated by monensin, concanavalin A, and cytochalasin
      D, orthovanadate treatment results in increased synthesis of the membrane
      proteinase MT1-MMP, that can catalyze the activation of progelatinase A. Protein
      tyrosine kinase inhibitors are able to prevent the increase of MT1-MMP mRNA, as
      shown by Northern blot and RT-PCR. In addition, orthovanadate potentiates the
      effects of monensin and concanavalin A. While treatment with monensin or
      concanavalin A result only in an increase of the putative activator MT1-MMP,
      orthovanadate also reduces the production of the specific inhibitor TIMP-2. These
      experiments implicate protein tyrosine phosphorylation in the signal transduction
      pathways which lead to the activation of progelatinase A.

PMID- 9784620
TI  - Energy metabolism in rat pancreatic acinar cells during anoxia and reoxygenation.
AB  - Mitochondrial energy metabolism was studied in isolated pancreatic acinar cells
      during anoxia up to 90 min and reoxygenation for 60 min. To identify critical
      alterations leading to the known postanoxic impairments in structure and function
      of acinar cells, adenine nucleotide levels and the rates of phosphorylating and
      non-phosphorylating respiration were determined. ATP levels and the total amount
      of adenine nucleotides strongly decreased as early as after 30 min of anoxia. The
      cells partially restored ATP and the total adenine nucleotides within 60 min of
      reoxygenation. Long-term anoxia caused an increase in the oligomycin-insensitive
      part of oxygen consumption. The respiratory capacity measured as uncoupled
      respiration progressively declined to 40% of controls after 90 min of anoxia.
      Fluorescence measurements showed that flavoproteins and mitochondrial pyridine
      nucleotides in reoxygenated cells after short-term anoxia were in a more reduced
      state than in aerobic controls, and were not fully oxidizable by uncoupling. It
      is concluded that long-term anoxia produces an irreversible loss of respiratory
      capacity leading to a limited ATP production. This functional impairment and the
      progressive damage to acinar cells may be relevant for pancreatic injuries such
      as acute pancreatitis or post-transplantation pancreatitis.

PMID- 9784621
TI  - The hydrolytic activity of bovine adrenal medullary plasma membranes towards
      diadenosine polyphosphates is due to alkaline phosphodiesterase-I.
AB  - A hydrolase activity directed against diadenosine 5',5"'-P1, P4-tetraphosphate
      (Ap4A) has been solubilised and partially purified from the plasma membrane
      fraction of bovine adrenal medullary chromaffin tissue in order to determine its
      relationship to alkaline phosphodiesterase-I/nucleotide pyrophosphatase (PDase-I,
      EC 3.1.4.1). Activity with the specific dinucleoside tetraphosphatase (EC 3.6.1.
      17) substrate Ap4A and with the non-specific PDase-I substrate thymidine 5'
      monophosphate p-nitrophenyl ester had Km and Vmax values of 2.0 microM and 600
      pmol/min/mg protein and 0.2 mM and 26 nmol/min/mg protein respectively and co
      chromatographed upon gel filtration and ion-exchange chromatography. Activity
      with the fluorescent substrates etheno-Ap4A and 4-methylumbelliferyl
      phenylphosphonate co-electrophoresed on native polyacrylamide gels. No activity
      was detected which exclusively hydrolysed Ap4A. Immunoblotting of the most
      purified fraction with an antibody against mouse PC-1, one of the major PDase-I
      family members, detected bands of 240, 120 and 62 kDa corresponding to PC-1
      dimer, monomer and proteolytic fragment. Therefore, the activity previously
      described as bovine adrenal chromaffin cell ecto(diadenosine polyphosphate
      hydrolase) (ecto-ApnAase) is a PDase-I, probably bovine PC-1.

PMID- 9784622
TI  - Behavior of N-phenylmaleimide- and p-phenylenedimaleimide-reacted muscle
      crossbridge heads.
AB  - The finding of Barnett et al. (Biophys. J. 61 (1992) 358) that NPM-reacted
      crossbridge heads do not bind strongly to actin in rigor solution is not easily
      interpreted in terms of the solution studies of Xie and Schoenberg (Biochemistry
      37 (1998) 8048) who found strong binding of NPM-reacted myosin subfragment-1 to
      actin in solutions devoid of MgATP. For this reason, the current work uses
      stiffness measurement to re-investigate the binding of rabbit skeletal muscle
      crossbridges to actin in rigor solution. It is found that NPM-reacted crossbridge
      heads bind strongly to actin in rigor solution providing one is extremely careful
      to reduce MgATP contamination to levels well below those that would have a
      detectable effect on unmodified fibers. The reason for this is that NPM-reacted
      crossbridge heads, which hydrolyze MgATP extremely slowly, are especially
      susceptible to contaminant MgATP. The new fiber results show a strong correlation
      with the solution results. A further manifestation of this correlation is that
      pPDM-reacted crossbridge heads are different from NPM-reacted ones in that, like
      in solution, they remain weakly binding to actin even at extremely low MgATP
      levels. The findings suggest that the covalent crosslinking of SH1 and SH2 by
      pPDM is likely playing a significant role in locking pPDM-reacted crossbridge
      heads in a weakly binding conformation.

PMID- 9784623
TI  - Tyrosine phosphorylation events during different stages of collagen-platelet
      activation.
AB  - Three groups of phosphoproteins have been distinguished, basing on the velocity
      and extent of phosphorylation in platelets stimulated with collagen. pp60c-src
      constituted the first group; the increase in its phosphorylation was the highest
      and most rapid (maximal in 30 s after the addition of collagen). pp80/85 and non
      identified protein of 65 kDa formed the second group; the increase in their
      phosphorylation was twice smaller than that of pp60c-src, and reached its maximum
      60 s after the addition of collagen. pp120, pp72syk, and two non-identified
      phosphoproteins of 90 and 75 kDa constituted the third group; the increase in
      their phosphorylation was 4-10-fold lower than that of pp60c-src and reached its
      maximum after 180 s. We conclude that the phosphorylation of pp60c-src is
      important for the change of shape of platelets, the phosphorylation of pp80/85
      and pp65 for the initiation of the formation of aggregates and the
      phosphorylation of the third group of phosphoproteins for the formation of
      massive aggregates. This conclusion was supported by using a monoclonal anti-GPIb
      antibody, which did not inhibit the shape change of platelets and did not inhibit
      pp60c-src phosphorylation. This antibody inhibited aggregate formation as well as
      tyrosine phosphorylation of proteins belonging to the second and the third group
      of phosphoproteins.

PMID- 9784624
TI  - Interactions of reduced and oxidized nicotinamide mononucleotide with wild-type
      and alphaD195E mutant proton-pumping nicotinamide nucleotide transhydrogenases
      from Escherichia coli.
AB  - The interaction of reduced nicotinamide mononucleotide (NMNH), constituting one
      half of NADH, with the wild-type and alphaD195E proton-pumping nicotinamide
      nucleotide transhydrogenase from Escherichia coli was investigated. Reduction of
      thio-NADP+ by NMNH was catalysed at approximately 30% of the rate with NADH.
      Other activities including proton pumping and the cyclic reduction of 3'-acetyl
      pyridine-NAD+ by NMNH in the presence of NADP+ were more strongly inhibited. The
      alphaD195 residue is assumed to interact with the 2'-OH moiety of the adenosine
      5'-phosphate, i.e., the second nucleotide of NADH. Mutation of this residue to
      alphaD195E resulted in a 90% decrease in activity with NMNH as well as NADH as
      substrate, suggesting that it produced global structural changes of the NAD(H)
      binding site. The results suggest that the NMN moiety of NADH is a substrate of
      transhydrogenase, and that the adenine nucleotide is not required for catalysis
      or proton pumping.

PMID- 9784626
TI  - The PLC1 encoded phospholipase C in the yeast Saccharomyces cerevisiae is
      essential for glucose-induced phosphatidylinositol turnover and activation of
      plasma membrane H+-ATPase.
AB  - Addition of glucose to glucose-deprived cells of the yeast Saccharomyces
      cerevisiae triggers rapid turnover of phosphatidylinositol, phosphatidylinositol
      phosphate and phosphatidylinositol 4,5-bisphosphate. Glucose stimulation of PI
      turnover was measured both as an increase in the specific ratio of 32P-labeling
      and as an increase in the level of diacylglycerol after addition of glucose.
      Glucose also causes rapid activation of plasma membrane H+-ATPase. We show that
      in a mutant lacking the PLC1 encoded phospholipase C, both processes were
      strongly reduced. Compound 48/80, a known inhibitor of mammalian phospholipase C,
      inhibits both processes. However, activation of the plasma membrane H+-ATPase is
      only inhibited by concentrations of compound 48/80 that strongly inhibit
      phospholipid turnover. Growth was inhibited by even lower concentrations. Our
      data suggest that in yeast cells, glucose triggers through activation of the PLC1
      gene product a signaling pathway initiated by phosphatidylinositol turnover and
      involved in activation of the plasma membrane H+-ATPase.

PMID- 9784625
TI  - cAMP inhibits linoleic acid-induced growth by antagonizing p27(kip1) depletion,
      but not interfering with the extracellular signal-regulated kinase or AP-1
      activities.
AB  - To understand the underlying signaling events of polyunsaturated fatty acid
      induced growth, we studied the effect of cAMP on early and delayed growth
      response events induced by linoleic acid in smooth muscle cells (SMC). cAMP
      significantly inhibited both basal and linoleic acid-induced DNA synthesis.
      Linoleic acid-induced early growth response events, such as activation of ERKs,
      induction of expression of c-fos and jun-B and stimulation of AP-1 activity,
      however, were not affected by cAMP. In contrast, linoleic acid-induced c-jun
      expression was blocked by cAMP. cAMP alone stimulated ERKs activation, c-fos and
      jun-B expression and increased AP-1 activity. Linoleic acid induced depletion of
      p27kip1 and increased CDK2 activity, events required for G1/S transition. In
      contrast to early growth response events, linoleic acid-induced G1/S transition
      signals were significantly inhibited by cAMP. These findings suggest that in
      addition to inducing immediate early growth response events, linoleic acid mimics
      growth factors in activating cell cycle events that are associated with G1/S
      transition in SMC and the negative regulation of linoleic acid-induced growth by
      cAMP is apparently due to its antagonism with linoleic acid-induced p27kip1
      depletion and CDK2 activation.

PMID- 9784627
TI  - The effect of prostaglandin E2 on cystine uptake and glutathione synthesis by
      human lung fibroblasts.
AB  - Prostaglandin E2 (PGE2) is an inflammatory mediator capable of regulating
      fibroblast cell proliferation, matrix protein production, and system A amino acid
      transport. System x-c amino acid transport is regulated by electrophilic agents
      and oxygen. The effect of PGE2 on the x-c system transport of cystine and the
      synthesis of glutathione by human lung fibroblasts was examined. Preincubation of
      fibroblast cultures with PGE2 decreased cystine uptake by 42%. Kinetic studies
      revealed a 42% decrease in the Vmax of the x-c system transporter in PGE2-treated
      fibroblasts; however, the apparent Km was not affected. The glutathione content
      of PGE2-treated fibroblasts was decreased by up to 25% of control. These results
      demonstrate that system x-c transport of cystine is regulated by PGE2 and suggest
      that the limited availability of intracellular cysteine inhibited glutathione
      synthesis.

PMID- 9784628
TI  - Role of rho proteins in agonist regulation of phospholipase D in HL-60 cells.
AB  - Rho family GTP-binding proteins have been demonstrated to play a role in the
      regulation of phospholipase D (PLD) activity. In the present study, we examined
      the role of Rho proteins in PLD activation in differentiated HL-60 cells using C3
      exoenzyme from Clostridium botulinum, which ADP-ribosylates and inactivates Rho
      proteins. Introduction of C3 exoenzyme into differentiated HL-60 cells by
      electroporation resulted in complete inhibition of PLD activity stimulated by
      formyl methionine-leucine-phenylalanine (fMLP) and ATP, two receptor agonists.
      Phorbol myristate acetate-induced PLD activation was also inhibited in C3
      exoenzyme-treated cells, but the inhibition was only partial. GTPgammaS-dependent
      activation of PLD, measured in the absence or presence of ATP in permeabilized
      cells, was also partially affected by C3 exoenzyme treatment. Thus, these results
      indicate that Rho proteins play a key role in receptor-mediated PLD regulation in
      differentiated HL-60 cells, but play a partial role in the in vivo action of PMA
      and in vitro action of GTPgammaS on PLD. ATP produced a significant enhancement
      of the in vitro effect of GTPgammaS on PLD activity, but the effect of ATP was
      not altered by inhibitors of serine/threonine and tyrosine kinases. However, it
      was markedly reduced by neomycin and accompanied by an increase in
      phosphatidylinositol 4,5-bisphosphate (PtdInsP2) synthesis. These data indicate
      that in permeabilized HL-60 cells, the stimulatory effect of ATP on PLD does not
      involve protein phosphorylation but is due to an increase in PtdInsP2.

PMID- 9784630
TI  - Management of fetal and neonatal alloimmune thrombocytopenia.
AB  - Fetal and neonatal thrombocytopenia can be induced by a maternal alloimmunization
      against fetal platelet antigens. Alloimmune thrombocytopenia occurs with an
      incidence of 1/1,000 livebirths and may present either with evidence of damage
      from a prenatal hemorrhage such as porencephaly or intrauterine death, or with
      active life-threatening bleeding during the neonatal period. It is due to the
      destruction of fetal platelets by alloantibodies reacting on specific antigenic
      sites. In Caucasians, the human platelet antigen 1a (HPA-1a) is the most
      frequently involved in alloimmune thrombocytopenias, accounting for 80-90% of the
      cases. Anti-HPA-5b is responsible for a further 5-15% of the cases. This article
      reviews the clinical aspects, the biological diagnosis and the management,
      including prenatal sampling and maternal therapy.

PMID- 9784629
TI  - Expression and activation of lyn in macrophages treated in vitro with cisplatin:
      regulation by kinases, phosphatases and Ca2+/calmodulin.
AB  - Cisplatin [cis-dichlorodiammine platinum (II)], a potent chemoimmunotherapeutic
      drug, activates macrophages to tumoricidal state which is inhibited by protein
      tyrosine kinase(s) inhibitor. Cisplatin induces protein tyrosine phosphorylation
      of a number of cellular proteins suggesting the involvement of protein tyrosine
      kinase(s) in the activation process of macrophages. Therefore, the effect of
      cisplatin treatment on the expression and activation of lyn, a protein tyrosine
      kinase of src family, in macrophages was investigated. The underlying mechanism
      of lyn expression and activation was also analyzed. Cisplatin treatment increased
      lyn expression and activation in macrophages within 5 min of treatment. The
      expression and activation of lyn were observed to be biphasic processes in
      cisplatin-treated macrophages with the first peak appearing at 15 min and the
      second peak at 2 h of treatment. The appearance of second phase of lyn activation
      and second phase of lyn expression were two unrelated processes. The second peak
      of lyn activation was produced by the autocrine action of some soluble product(s)
      of cisplatin-treated macrophages, whereas the second phase of lyn expression was
      due to some intracellular factor. It was further observed that cisplatin-induced
      lyn expression and activation involves serine/threonine phosphatases 1/2A,
      protein tyrosine phosphatases, protein tyrosine kinase and protein kinase C. It
      was also observed that Ca2+/calmodulin and calmodulin-dependent kinases are
      involved in the regulation of cisplatin-induced lyn expression and activation in
      macrophages.

PMID- 9784631
TI  - Clinical usefulness of maternal odor in newborns: soothing and feeding
      preparatory responses.
AB  - This study assessed the responsiveness of newborn breast- and bottle-fed infants
      to presentations of maternal odor. Maternal odor was presented for 1 min to
      crying, sleeping or awake newborns. The odors were: (1) own mother's odor -
      presentation of a hospital gown worn by the baby's mother, (2) other mother's
      odor - presentation of a hospital gown of another newborn baby's mother, (3)
      clean gown - presentation of a clean hospital gown and (4) no gown - no gown
      presented. The results indicated that crying babies stopped crying when either
      own mother or other mother odor was presented. Awake babies responded
      specifically to their own mother's odor by increasing mouthing. These results
      suggest that the practice of presenting the mother's odor to a distressed infant
      is of clinical usefulness since it was capable of attenuating crying. The results
      also characterized a role for maternal odor with respect to feeding since
      presentation of the infant's own mother odor increased mouthing. Thus,
      presentation of maternal odor may also be useful in enhancing nipple acceptance
      and feeding in newborns.

PMID- 9784632
TI  - Decreasing reticulocyte counts associated with declining post-dose erythropoietin
      plasma levels in anaemia of prematurity.
AB  - A prospective sequential, multicentre trial was conducted to determine the
      association between erythropoietin (EPO) plasma levels and the erythropoietic
      response to recombinant human erythropoietin (r-HuEPO) during long-term treatment
      of premature infants. Twenty-nine infants, gestational ages 26-34 weeks and
      postnatal ages more than 14 days, received 600 IU r-HuEPO per kg per week divided
      into three doses subcutaneously for haemoglobin levels less than 120 g/l or
      haematocrit less than 36% over a period of 4 weeks. Eight additional patients
      were studied for a total of 10 weeks. EPO plasma concentrations and haematologic
      parameters were measured prior to the onset of treatment and at 2-weekly
      intervals thereafter. Treatment with r-HuEPO resulted in a median increase in
      corrected reticulocyte counts of 2.5% (range 0.2-4.6%) above patient's baseline,
      thereafter a decrease was observed. In the 8 patients followed for 10 weeks
      reticulocyte counts declined significantly during weeks 6-10 when compared with
      the first 4 weeks (p < 0.005). Median 72-hour post-dose EPO plasma levels
      increased significantly (p < 0.0001) to 57.3 mU/ml (range 5.0-160) above
      patient's baseline after the first injection, but declined progressively
      thereafter until they approached baseline values at week 10. CONCLUSION: R-HuEPO
      treatment after the first month was associated with a decrease in post-injection
      plasma levels and a decrease in erythropoietic response. This decrease in
      erythropoietin's efficacy and the decline observed in post-dose EPO plasma levels
      may be causally related.

PMID- 9784633
TI  - Effect of two types of fish oil supplementation on plasma and erythrocyte
      phospholipids in formula-fed term infants.
AB  - We studied the effect of docosahexaenoic acid (DHA) supplementation of infant
      formulas on fatty acid composition of blood phospholipids in term infants. Two
      fish oil supplemented formulas containing 0.45 wt% DHA and high (0.35%) or low
      (0.10%) eicosapentaenoic acid (EPA) were fed for 42 days and compared with a
      standard formula and breast milk. Infants fed supplemented formulas and breast
      milk had similar time-dependent changes for DHA from birth to day 42, i.e.,
      slight decreases in plasma phospholipids and erythrocyte phosphatidylcholine and
      no change in erythrocyte phosphatidylethanolamine. Low-EPA formula prevented EPA
      accumulation but did not limit the significant decrease in arachidonic acid (AA)
      noted in infants fed high-EPA formula. These results suggest that term infant
      formulas should be supplemented with DHA-rich EPA, low fish oil and AA to achieve
      a fatty acid status in formula-fed infants similar to that of breast-fed infants.

PMID- 9784634
TI  - Gut regulatory peptide levels in bovine fetuses and their dams between the 3rd
      and 9th months of gestation.
AB  - Several gut regulatory peptides were measured by radioimmunoassay between 3 and 9
      months of gestation in the plasma of 91 bovine fetuses and their dams, in fetal
      gastric content and in amniotic fluid. During gestation, plasma peptide
      concentrations did not change in cows. Likewise, fetal plasma concentrations of
      cholecystokinin, somatostatin, secretin and vasoactive intestinal polypeptide
      showed no variation while those of gastrin, pancreatic polypeptide and gastric
      inhibitory polypeptide increased during the last 6 months. Peptide levels in the
      fetus were higher than or equal to maternal concentrations. At 8-9 months of
      gestation, gastrin, CCK, secretin and somatostatin concentrations in amniotic
      fluid were lower than those measured in fetal gastric content and in maternal and
      fetal plasma. Therefore, a substantial endogenous endocrine production of
      regulatory peptides by the fetus probably exists as early as the third month of
      gestation, accompanied by a release into the lumen of the gut.

PMID- 9784635
TI  - Platelet-activating factor is an important mediator in hypoxic ischemic brain
      injury in the newborn rat. Flunarizine and Ginkgo biloba extract reduce PAF
      concentration in the brain.
AB  - Hypoxic-ischemic encephalopathy is still a very important cause of neonatal
      mortality and morbidity. Recently, platelet-activating factor (PAF) has been
      accused of being responsible for the neuronal damage in hypoxic-ischemic brain.
      We investigated tissue PAF concentrations in hypoxic-ischemic brain injury in
      immature rats. Endogenous PAF concentration in brain tissue showed a marked
      increase in hypoxic-ischemic pups (85.6 +/- 15.5 pg/mg protein) when compared to
      that of control (9.05 +/- 3.1 pg/mg protein). In addition, we examined the
      effects of flunarizine, a selective calcium channel blocker, and Ginkgo biloba
      extract (EGb 761) on endogenous PAF concentration in hypoxic-ischemic brain
      injury. Endogenous PAF concentrations in both flunarizine-pretreated (16.6 +/-
      4.8 pg/mg protein) and EGb 761-pretreated (33.5 +/- 8.9 pg/mg protein) pups were
      significantly lower than the untreated group. These results indicate that PAF is
      an important mediator in immature rat model of cerebral hypoxic-ischemic injury.
      The suppressor effect of flunarizine and EGb 761 on PAF production may open new
      insight into the treatment of hypoxic-ischemic brain injury.

PMID- 9784636
TI  - Postasphyxial reoxygenation reduces the activity of Na+/K+-ATPase in the
      erythrocytes of newborn piglets.
AB  - The aim of our study was to determine whether the impairment of Na+/K+ pump is
      detectable in erythrocytes during hypoxia and reoxygenation. Acute asphyxia was
      induced in 10 newborn piglets for 1 h by bilateral pneumothorax. The Na+/K+
      ATPase activity, Na+, K+ and ATP content of RBCs were determined in baseline
      condition (paO2: 60.4 +/- 9.3 mm Hg), at the end of the hypoxic period (1 h)
      (paO2: 30.2 +/- 10.3 mm Hg), then hourly during the reoxygenation phase (2, 3, 4
      h) (paO2: 54.8 +/- 9.0, 56.1 +/- 8.7, 57.2 +/- 9.6 mm Hg). The Na+/K+-ATPase
      activity was constant during the first 3 h. However, it decreased at 4 h (676 +/-
      168 versus baseline 833 +/- 141 U, p < 0.05). The highest ATP content was
      measured also at this point (4.32 +/- 0.57 versus baseline 3.27 +/- 0.45 mmol/l
      RBC, p < 0.01). The Na+ content was lower at 1 and 2 h (14.0 +/- 1.8; 13.8 +/-
      1.2 versus baseline 15.7 +/- 1.2 mmol/100 g Hb, p < 0.05), but later it became
      normal. Plasma monovalent cationic levels and intracellular K+ content did not
      alter during the experiment. Our results indicate that the deterioration of
      enzyme activity occurs within the same time-frame that previously described
      morphological alterations in brain tissue develop, so the RBC Na+/K+-ATPase
      activity might reflect the progress of posthypoxial brain damage.

PMID- 9784637
TI  - Effect of magnesium sulfate on kidney function in the newborn rabbit.
AB  - The aim of this study was to investigate the acute, short-term effects of the
      intravenous (i.v.) administration of magnesium (Mg) sulfate on renal function in
      the newborn rabbit. Eight anesthetized and mechanically ventilated, normoxemic,
      newborn New Zealand white rabbits were studied. We measured mean arterial blood
      pressure (MAP), urine volume (V), glomerular filtration rate (GFR), renal plasma
      flow (RPF) and calculated renal blood flow, filtration fraction (FF) and renal
      vascular resistance (RVR) under control conditions and in two experimental
      periods after the i.v. Mg sulfate load. Mg sulfate administration in a dose 100
      mg/kg followed by 50 mg/kg/h caused a significant fall (p < 0.001) in MAP, GFR
      and RPF, whereas the RVR increased (p < 0.01). FF did not change significantly
      (p: NS/0.05) and V remained constant. These results show that the acute i.v.
      administration of Mg sulfate to newborn rabbits causes systemic vasodilatation
      with a fall in MAP. The increase in RVR, without consistent change in FF,
      suggests that the renal vasculature of the 'immature' neonatal rabbit reacts to
      these changes by preferential afferent arteriolar vasoconstriction.

PMID- 9784638
TI  - Ultrasound-guided gene transfer to hepatocytes in utero.
AB  - OBJECTIVES: Several inherited liver diseases are associated with a progressive
      course that begins early in life. Such disorders may be amenable to treatment
      with gene transfer in the fetal or neonatal period. METHODS: We used ultrasound
      guidance to deliver an adenoviral vector to the liver of 28-day gestation fetal
      rabbits by cardiocentesis. beta-Galactosidase reporter gene expression in
      hepatocytes was analyzed 3, 7, and 21 days after vector delivery. Using this
      nonsurgical approach, the viral vector was efficiently delivered into the fetal
      circulation. RESULTS: The liver was the main organ targeted by this route of
      administration with up to 40% of the hepatocytes beta-galactosidase positive in
      some animals. The beta-galactosidase expression in hepatocytes gradually declined
      between 3 and 21 days following gene transfer. Associated with the decline in
      gene expression, an increased number of inflammatory cells were noted in the
      livers of adenoviral vector treated animals. This suggests that an immune
      response limits the duration of gene expression in the fetal rabbit, similar to
      the findings in postnatal animals. CONCLUSIONS: This animal model and vector
      delivery method may be useful for evaluating gene transfer to the fetus with
      viral and nonviral vectors. Further modifications of the adenoviral vector to
      reduce immunogenicity may enhance the duration of expression.

PMID- 9784639
TI  - A case of congenital familial short femur diagnosed prenatally.
AB  - A fetus at 24 weeks of gestation had been suspected of congenital familial
      bilateral short femur. The Japanese mother, 41 years old and 139 cm in height
      presented with bilateral short femur herself. The mother had two affected aunts
      and one affected daughter in her family history. Ultrasound examination was given
      to the mother for the first time at 24 weeks of gestation and it revealed
      bilateral short femur of 30 mm in length on the right and 31 mm on the left femur
      of the fetus. Other examinations were entirely normal and the pregnancy resulted
      in a full-term spontaneous vaginal delivery to a male baby. Birth weight was
      2,790 g and the 1 and 5 min Apgar scores were at 8 and 10. Diagnosis was
      confirmed by skeletal radiographs.

PMID- 9784640
TI  - Debate about ultrasound screening policies.
AB  - Routine ultrasound examination is defined as a screening procedure performed on
      the total obstetric population usually at 18-20 weeks of gestation as opposed to
      the selective use of ultrasound that might provide more information for a problem
      that is suspected on clinical grounds. Standard ultrasound examination includes a
      comprehensive examination of fetal anatomy as part of routine ultrasound. It is
      important for the clinician to realise that the comprehensive examination of
      fetal anatomy is an essential, not optional, part of the routine examination.
      Screening may lead to unnecessary anxiety if there is a false-positive result, or
      to a false sense of security if there is a false-negative result. The routine
      offering of obstetric ultrasound screening is the central issue in the general
      question of whether every woman should receive an obstetric ultrasound
      examination. The majority of countries have adopted the following diagnostic
      strategy. All pregnancies must be ultrasonographically tested in accordance with
      the protocols commonly recommended. The ultrasonography done at 18-20 weeks,
      which is known to be fundamental for diagnosing prenatal malformations, must
      always be performed at level II. High-risk pregnancies of malformations are to be
      selected in the first level of screening and referred to level II for further
      study. There is extensive literature neither supporting an improvement in
      perinatal morbidity or mortality nor an overall reduction in unnecessary
      intervention with routine ultrasound. The role of routine ultrasonography and its
      validity as a screening test for fetal malformation in a low-risk population is
      still the object of debate.

PMID- 9784641
TI  - Effect of in utero infusion route on lymphocyte distribution in fetal rat
      tissues.
AB  - Infusion of cells into the fetus is a new form of intrauterine therapy for
      several genetic disorders. The effect of in utero infusion routes on labelled
      lymphocyte distribution in fetal rat organs was investigated. Fetuses, 14-16 days
      of gestation, were infused in utero with a Hoechst 33342 (bis-benzamide) labelled
      lymphocyte and FITC-labelled polystyrene bead mixture via four routes:
      intraperitoneal, intraplacental, intra-amniotic, and intravenous. The
      distribution within tissues was evaluated in frozen sections of placenta and
      fetal organs. Our results suggest that among the four routes tested, the
      intravenous route offered the possibility to reach easily fetal organs without
      any cell loss and yielded higher cell and bead concentrations in fetal organs,
      especially in the liver and in the kidney. In conclusion, the intravenous route
      seems to be appropriate for hematopoietic cell transplantation in the developing
      fetus.

PMID- 9784642
TI  - Fetal and neonatal hypertension in twin-twin transfusion syndrome: a case report.
AB  - We report a case of fetal systemic hypertension. This occurred in an ex-donor
      twin soon after coagulation of chorionic vessels and amniodrainage performed for
      severe twin-twin transfusion syndrome during the 2nd trimester of pregnancy.
      Systemic hypertension was suspected because of a high systolic velocity through
      the tricuspid valve, and Bernoulli's equation was used to estimate the right
      intraventricular pressure. As both pulmonary arteries and ductus arteriosus were
      normal, the pressure in the aorta was considered to be equal to that in the right
      ventricle (60 mm Hg). Fetal systemic hypertension could have happened either
      because of a dramatic increase in placental resistances in the territory of the
      ex-donor twin or by reversal of the fetofetal transfusion pathological process.

PMID- 9784643
TI  - Persisting spongy myocardium. A case indicating the difficulty of antenatal
      diagnosis.
AB  - Persisting spongy myocardium (also known as noncompaction of the ventricular
      myocardium) is a rare and special form of cardiomyopathy. The few cases reported
      in the literature were detected postnatally and involved a high rate of
      cardiovascular complications. This anomaly of endomyocardial morphogenesis, which
      occurs during the embryonic phase at the stage of cardiac partitioning, is
      characterised by an excessive number of prominent trabeculae and by
      intertrabecular recesses within the myocardial wall. Antenatal detection is
      difficult in the absence of an associated malformation, which is the general
      situation. We report a case of antenatal cardiomyopathy which led to therapeutic
      abortion. The diagnosis of persisting spongy myocardium was made during
      fetopathologic examination.

PMID- 9784644
TI  - Successful management of severe idiopathic thrombocytopenia in the second
      trimester of pregnancy.
AB  - This paper describes a case of severe idiopathic thrombocytopenia in a
      primigravida. The disorder became symptomatic at 22 weeks gestation with a
      platelet count of 20,000/microliter. The existence of chronic idiopathic
      thrombocytopenia under remission was strongly suspected, but could not be
      documented. The patient was treated with oral corticosteroids over a period of 7
      weeks. During this period, she also had three cycles of high-dose intravenous
      globulin. This treatment produced a transient improvement, but the platelet count
      fell to 4,000/ microl by the 29th gestational week. Caesarean section was carried
      out for maternal indication a week later, following a fourth intensified course
      of gamma-globulin, coupled with platelet transfusions and low-dose vinblastine.
      Splenectomy was not performed. Potentially life-threatening thrombocytopenia
      persisted for 6 weeks post partum. Despite the presence of circulating
      antiplatelet globulin in the maternal blood and the antenatal use of vinblastine,
      the infant was entirely unaffected and thrived.

PMID- 9784645
TI  - Does the hemoglobin concentration in fetal blood interfere with the accuracy of
      fetal reflection pulse oximetry?
AB  - OBJECTIVE: Our goal was to investigate the influence of the fetal hemoglobin (Hb)
      concentration on the accuracy of reflection pulse oximetry. METHODS: 179 fetuses
      were monitored by a reflection pulse oximetry system (RPOX MK2). Pulse oximetry
      measurements (SO2POX) were compared with the oxygen saturation and pH of
      umbilical artery and vein (UA-, UV-SaO2) immediately after delivery. Correlation
      and linear regression analyses were performed. Because it is unknown whether low
      or high Hb concentrations might interfere with the SO2POX measurements, the
      influence of the Hb level on the correlations was evaluated by weighting the
      linear regression in both ways; by Hb concentrations as weighting factor and as
      an inverse weighting factor (1/Hb). RESULTS: There was a significant correlation
      between SO2POX and UV-SaO2 (for the last 10 min of delivery, r = 0.45, p <
      0.0005) but not with pH or UA-SaO2. Linear regression analysis between SO2POX and
      UV-SaO2 showed a multiple R of 0.45. Hb concentration in fetal blood ranged from
      9.2 to 20.5 mg/dl. The weighted regression indicated a multiple RHb of 0.49,
      which did not differ by the inverse weighting (multiple Rinverse Hb: 0.49).
      CONCLUSIONS: Pulse oximetry measurements seem to reflect oxygen saturation in
      fetal blood, however further improvement is necessary. The Hb concentration in
      fetal blood does not interfere with the accuracy of fetal pulse oximetry and need
      not be taken into consideration in calibration curves.

PMID- 9784646
TI  - Changes in uterine artery doppler velocimetry in pregnant patients undergoing
      glucose tolerance test may predict adverse outcome in later pregnancy: a
      preliminary study.
AB  - OBJECTIVE: Previous studies have demonstrated that high glucose levels often
      cause increased placental resistance to blood flow. The present study was
      undertaken to assess whether any changes in placental vascular resistance would
      occur following a standard glucose tolerance test. METHODS: Doppler velocimetry
      of uterine, intraplacental and umbilical vessels was performed before and after
      administration of glucose tolerance test. RESULTS: The uterine circulation
      demonstrated abnormal indices in patients that later developed placental
      insufficiency. CONCLUSION: This preliminary study demonstrated that following a
      glucose tolerance test significant changes seem to occur in the uteroplacental
      but not in the fetoplacental circulation of pregnancies destined to develop
      preeclampsia or intrauterine growth restriction.

PMID- 9784647
TI  - Congenital rapidly fatal form of nemaline myopathy with fetal hydrops and
      arthrogryposis. A case report and review.
AB  - A new lethal case of nemaline myopathy is reported. The diagnosis was made by
      postmortem muscle biopsy. The child died before his first day of life. This is
      one of the very rare cases of nemaline myopathy with severe antenatal
      ultrasonographic signs: fetal hydrops and arthrogryposis. In a review of the
      literature other cases of the congenital rapidly fatal form are found, some of
      them with clinical decrease of fetal movements but only few authors report
      ultrasonographic signs. The diagnostic, histopathogenic, genetic and evolutive
      aspects of this heterogeneous disorder are analyzed. This congenital
      nonprogressive myopathy is not as benign as previously thought and may be an
      etiology of the lethal form of arthrogryposis multiplex congenita. The existence
      of ultrasonographic antenatal signs seems to be a factor of poor prognosis. In
      spite of recent genetic discoveries, there is at present no specific antenatal
      diagnosis. Consequently, muscle biopsy in lethal cases is very important to allow
      a genetic counselling; however, in utero fetal biopsy has never been performed in
      such cases.

PMID- 9784648
TI  - Detection of an obstructive membrane in the ductus arteriosus of a fetus using
      high frame rate echocardiography.
AB  - We examined a fetus at 38 weeks of gestation because of marked disproportion in
      size of the left and right ventricles. A membrane was detected at the distal end
      of the ductus arteriosus with significant flow gradient through it. New
      echocardiographic technologies such as high frame rate imaging and dynamic beam
      focusing increase spatial and temporal resolution and enhance more precise
      anatomical diagnosis in the fetus. This ductal membrane might have been related
      to the transient tachypnea from which the baby suffered after birth.

PMID- 9784649
TI  - Detection and measurement of fetomaternal hemorrhage following diagnostic
      cordocentesis.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of cordocentesis
      on fetomaternal hemorrhage (FMH). METHODS: One hundred and three diagnostic
      cordocenteses, without any other associated procedure, were performed at 23-40
      weeks' gestation. FMH was detected using the Kleihauer-Betke staining of maternal
      blood taken immediately before and after cordocentesis. RESULTS: Significant FMH
      occurred after 40 (38.8%) of the 103 procedures. An increased risk of fetal
      bleeding was associated with both an anterior placenta (odds ratio (OR) 5.89; 95%
      confidence interval (CI) 2.27-15.3; p < 0. 001) and a transplacental
      cordocentesis (OR 37.0; 95% CI 2.15-636; p < 0.001). The volume of FMH was
      greater after cordocentesis with an anterior placenta (90th percentile 6.20 ml)
      than after cordocentesis with a lateral (90th percentile 4.58 ml) or posterior
      placenta (90th percentile 1.35 ml) (p < 0.001). After fetal blood sampling,
      significant FMH occurred more frequently with a procedure duration of 3 min or
      more (OR 4.45; 95% CI 1.70-11.7; p = 0.002) and with two or more needle
      insertions (OR 4.65; 95% CI 1.80-12.1; p = 0.001). CONCLUSION: FMH following
      cordocentesis may be related to placental injuries. This event is influenced by
      placental location, procedure duration and the number of needle insertions.

PMID- 9784650
TI  - Assessment of the risk of fetal loss after the coelocentesis procedure using a
      baboon model.
AB  - OBJECTIVES: The aims of this study were to gain some insight with regard to the
      safety of the coelocentesis procedure and, to determine pH, pCO2, and base excess
      status of the extracoelomic fluid 40 days after fertilization. METHODS: Twenty
      eight timed-mated baboons from the breeding colony of the Biological Resource
      Laboratory at the University of Illinois at Chicago were studied. The initial 19
      animals were used to determine the ultrasonographic relations between the
      different compartments of the gestational sac from 38 to 62 days of pregnancy.
      Under aseptic conditions, in 9 animals coelocenteses were then performed, under
      continuous transvaginal ultrasound guidance to avoid the amniotic or yolk sacs.
      Extracoelomic fluid (1-5 ml) was aspirated using 10-ml syringes. Only one attempt
      of sampling was performed in each of the 9 animals. Extracoelomic fluid pH, pCO2,
      and base excess were compared with maternal femoral venous blood. Pregnancies
      were followed by transabdominal ultrasound evaluations on day 3 after the
      procedure and weekly until day 140 after fertilization. RESULTS: Extracoelomic
      fluid could be aspirated easily using a 20-gauge needle. Only one pregnancy loss
      was detected within 3 days after the procedure. No complications occurred in the
      remaining 8 pregnancies. Extracoelomic fluid pH (7.45 +/- 0.01) and pCO2 (39.9 +/
      2.4 mm Hg) were significantly different from maternal femoral venous blood pH
      (7.41 +/- 0.01) and pCO2 (47.1 +/- 1.4 mm Hg; p < 0.02), while base excess values
      were similar. CONCLUSIONS: This preliminary study performed at 40 days after
      fertilization in the baboon model suggests that the coelocentesis procedure is
      technically simple and presents a relatively low risk to mother and fetus if a 20
      gauge needle is used and the amount of aspirated extracoelomic fluid is <3 cm3.
      At this gestational age, the extracoelomic fluid is more alkalotic than maternal
      femoral venous blood.

PMID- 9784651
TI  - The role of the invariant chain in mucosal immunity.
AB  - The invariant chain (Ii) due to its intimate association with major
      histocompatibility complex (MHC) alpha and beta chains is a determining element
      in the development of immune responses. Ii plays a major role in the assembly,
      the intracellular transport and peptide selection by class II MHC. A segment of
      Ii designated as CLIP (class II-associated Ii peptide) binds into the antigen
      binding site of class II MHC molecules until class II MHC reach intracellular
      compartments that contain peptides from internalized antigens. This association
      limits the self endogenous peptides that can bind to class II MHC molecules. The
      removal of CLIP from class II MHC catalyzes the binding of antigenic peptides and
      their subsequent cell surface expression. An isoform of Ii, known as chondroitin
      sulfate-modified Ii (IiCS), that is surface-expressed enhances T cell activation
      while acting as a coreceptor for CD44. The expression of class II MHC molecules
      by mucosal epithelial cells has generated interest in the role that these cells
      may have in mucosal immunity. Since in classical antigen-presenting cells (APC)
      the biology of class II MHC is regulated by Ii, it is necessary to bring into
      perspective the known functions of Ii in conventional APC to understand the role
      that Ii may play in mucosal epithelial cells as potential regulators of local
      immune responses.

PMID- 9784653
TI  - Identification of allergens in oilseed rape (Brassica napus) pollen.
AB  - BACKGROUND: Pollen from oilseed rape (OSR), Brassica napus, an increasingly
      cultivated oilplant from the Brassicaceae, has been recognized as a potential
      cause of allergic sensitization. Allergens have been hardly investigated.
      METHODS: We characterized IgE binding proteins in OSR pollen by immunoblot,
      immunoblot inhibition and specific monoclonal antibodies using sera from 89
      patients sensitized to OSR. RESULTS: Two low-molecular-weight allergens of 6/8 kD
      and 14 kD as well as a high molecular-weight cluster (27-69 kD) comprising six
      cross-reactive peptides could be identified. The three allergens were recognized
      by 50, 34 and 80% of patients, respectively. Immunoblot IgE binding to OSR could
      be totally inhibited by rye pollen and moderately by birch pollen (6/8 and 14 kD)
      while mugwort had little effect. An anti-profilin-specific monoclonal antibody
      bound specifically to a 14-kD protein in OSR. Binding to the 6/8-kD rape allergen
      could be effectively inhibited by rAln g 2, a calcium-binding protein from alder.
      Periodate treatment led to a significant reduction in IgE binding to the 27 to 69
      kD OSR allergens indicating that carbohydrate determinants are involved in IgE
      binding. OSR proteins were capable to quench IgE binding to timothy grass pollen
      proteins of >/=60 kD suggesting that grass pollen group 4 allergens cross-react
      with the 27 to 69-kD cluster in OSR. CONCLUSIONS: The data demonstrate that OSR
      pollen is allergenic and indicate that the identified allergens represent cross
      reacting homologues of well-known pollen allergens, i.e. calcium-binding
      proteins, profilins, and high-molecular-weight glycoproteins. Via cross
      reactivity, exposure to OSR pollen may be a prolonging and aggravating factor in
      underlying birch and grass pollen allergy.

PMID- 9784654
TI  - Effects of structure modifications on IgE binding properties of serum albumins.
AB  - BACKGROUND: Bovine serum albumin (BSA) is one of the most widely studied
      proteins; its structure is well-known and its antigenic characteristics have been
      described in studies performed in in vitro and animal models. The aim of our work
      was to evaluate the role of BSA conformation in its antigenicity (recognition by
      circulating IgEs from allergic children). METHODS: This study was performed using
      electrophoresis associated with the immunoblotting technique, where sera from
      children sensitized to BSA (as shown by double-blind placebo-controlled food
      challenge) were used. RESULTS AND DISCUSSION: Heat treatment and chemical
      denaturation (SDS treatment) are not able to decrease the BSA capability to bind
      circulating IgEs. Only by reducing treatment with 2-mercaptoethanol is it
      possible to modify but not to eliminate the antigenicity of this protein. The
      reactivity to other serum albumins from different animal species was also
      investigated and in this study we show a direct correlation between the number of
      IgE-mediated responses observed in immunoblotting and the percentage of sequence
      identity (phylogenetic similarity) of serum albumins. CONCLUSION: Data obtained
      in this research indicate that serum albumin antigenicity is only partially
      correlated to its native three-dimensional structure.

PMID- 9784652
TI  - Identification of the Schistosoma japonicum 22.6-kDa antigen as a major target of
      the human IgE response: similarity of IgE-binding epitopes to allergen peptides.
AB  - Human resistance to reinfection with Schistosoma mansoni and Schistosoma
      haematobium correlates with elevated IgE titers against worm antigens (soluble
      worm antigen preparation, SWAP). In S. mansoni infection, low levels of
      reinfection following chemotherapy are associated with the recognition of a
      cloned tegumental protein Sm22.6. Because of potential species-specific
      differences in resistance to schistosomes, we attempted to identify Schistosoma
      japonicum antigens recognized by human IgE. Following a survey of 176 infected
      individuals in Leyte, Philippines, we show that IgE antibodies from the majority
      of older, high-IgE/SWAP responders recognize antigens in the 22 (Sj22)-, 45-, 78-
      and 97-kDa range in SWAP. Limited IgE cross-reactivity between Sj22 and Sm22 was
      observed following a comparison of Filipino IgE responses to these antigens. The
      antigen was cloned from an adult S. japonicum lambda-ZAP cDNA library (Mindoro
      strain) by immunoscreening with pooled high-titer IgE antisera and a rabbit anti
      Sj22 polyclonal antibody. The deduced amino acid sequence of the identified cDNA
      clone, MJ-1, showed significant homology to Sm22.6 (74%) and Sj22.6 (99%).
      Although the molecular sequence of Sj22.6 has already been reported, this is the
      first demonstration of its recognition by human IgE, thereby strengthening its
      potential as a vaccine candidate. Using an overlapping peptide approach, four IgE
      binding epitopes were identified in Sj22.6, two of which exhibited similarities
      to known IgE-binding epitopes from codfish (Gad c 1) and beta-lactoglobulin
      related allergens. These findings suggest that allergy and protective immunity to
      helminth infection may be linked by the structural similarities of epitopes
      recognized by human IgE.

PMID- 9784655
TI  - Neoallergens in heated soybean hull.
AB  - BACKGROUND: During the process of harvest, transport and storage, microbial and
      mold contamination can raise the temperature of soybeans to 75 degreesC or
      higher. The purposes of this study were (1) to evaluate the allergenicity of
      fresh and stored soybean hulls and (2) to ascertain whether heat alters the
      allergenicity of stored soybean hulls. METHODS: Allergen extracts were prepared
      from (1) stored soybean hulls, (2) fresh soybean hulls and (3) stored soybean
      hulls heated to 37 degreesC (E1), 55 degreesC (E2) and 80 degreesC (E3) or kept
      at room temperature (E4) for 16 h. Individual serum from 68 soybean asthmatic
      (SA) subjects, 30 nonallergic subjects and two serum pools made from 4 SA sera
      and 4 sera from asthmatics not sensitive to soybean were studied. All sera and
      serum pools were assayed for content of specific IgE (radioallergosorbent test)
      and IgG4 (ELISA). The following additional studies were done for extracts E1-E4:
      (1) SDS-PAGE, (2) SDS-PAGE/Western blot for specific IgE and IgG4 using both
      serum pools, and (3) study of the effects of heat on inhibiting activity of the
      extracts prepared from stored soybean hulls using the pool of SA sera. RESULTS:
      Test results demonstrated a reduced binding of specific IgE and IgG4 to fresh
      soybean hull extract compared to stored soybean hull extract, and an increased
      binding for heated extracts (E1-E3) compared to unheated ones (E4). Moreover,
      there was an increase in potency for IgE and IgG4 bindings for the heated (E1-E3)
      compared to unheated (E4) extract, as measured by the amount of protein to
      produce 50% inhibition. Several protein bands with a molecular weight (MW) higher
      than 20 kD were absent from the SDS-PAGE for E3 but were present in E1, E2 and
      E4, and a new protein band (MW 15.3 kD) appeared for E3 only. Two new protein
      bands, with MWs of 15.3 and 10 kD, which bind specific IgE, were present on
      Western blot and one of the 3 main soybean hull allergens, probably Gly m 2,
      disappeared in E3. IgG4 Western blot showed similar results, but only the 10 kD
      protein band was present. CONCLUSION: The results demonstrate that soybean hull
      allergenicity is affected by heat, and suggest that the heat generated during
      storage and transport of soybeans could generate 2 new allergen determinants or
      increases in epitope exposure as a result of conformational changes. The
      significance of these new IgE and IgG4 binding proteins has yet to be determined.

PMID- 9784656
TI  - Autoantibodies in Estonia and Sweden, populations with different responses to
      allergens.
AB  - BACKGROUND: There are substantial differences in immune-mediated disease
      prevalence between different countries and populations which cannot be explained
      by genetic variability. AIMS: To compare the prevalence of antinuclear (ANA),
      antimitochondrial, antireticulin, liver-kidney microsomal, parietal cell, thyroid
      microsomal and double-stranded DNA (dsDNA) antibodies among adults aged 20-44
      years in two towns, i.e. in Tartu, Estonia (n = 448) and in Uppsala, Sweden (n =
      532) with a low and a high prevalence of allergy. METHODS: For autoantibody
      detection, standard indirect immunofluorescence tests on tissue and Chritidia
      lucilia antigenic preparations were used (sera were diluted starting from 1:10).
      RESULTS: The prevalence of ANA was lower in Tartu than in Uppsala (3 vs. 10%
      among males and 11 vs. 16% among females; p<0.01 and p<0.1, respectively).
      Furthermore, dsDNA antibody-positive cases were only identified in Uppsala. The
      largest difference between the two populations was revealed for IgM type ANA,
      both among males (1 vs. 6%; p<0.02) and females (5 vs. 11%; p<0.01). In addition,
      the antibody titers were lower in Tartu than in Uppsala (p<0.05). The prevalence
      of other autoantibodies was similar in the two towns. CONCLUSIONS: The findings
      could support that Th2-like immune responses are commoner in Sweden than in
      Estonia, as previously suggested by the higher prevalence of allergy.

PMID- 9784657
TI  - Exogenous interleukin-3 enhances IL-4 production by splenic CD4+ cells during the
      early stages of a Trichinella spiralis infection.
AB  - Treatment with recombinant interleukin-3 (rIL-3) augmented IL-4 production of
      spleen cells in mice infected with Trichinella spiralis. In a previous report, we
      showed that treatment with rIL-3 accelerated IgE responsiveness in mice. We have
      examined IL-4 and interferon (IFN)-gamma production by spleen cells from both rIL
      3-treated and untreated mice during the early stages of infection. The results
      indicated that IL-4 production was enhanced in rIL-3-treated mice compared to
      that in untreated mice. In contrast, there was no difference in IFN-gamma
      production between the two groups. Augmentation of IL-4 production was dependent
      on the dose of rIL-3 injected before infection. To examine if the treatment with
      rIL-3 affects T cell function, spleen cells from mice treated with various doses
      of rIL-3 were cultured under the stimulation with anti-CD3 (T cell receptor
      complex) mAb and then assessed for cytokine production. IL-4 production increased
      depending on the dose of rIL-3, while IFN-gamma production did not. Furthermore,
      spleen cells were separated by surface markers, Thy1.2, CD4 and CD8. Thy1. 2+
      cell population responded significantly to produce IL-4 after anti-CD3
      stimulation, when compared with IL-4 production of Thy1.2- cell population. A
      major producer of IL-4 in T cells was CD4+ cell population but not CD8+ cell
      population. IL-4 production was suppressed in rIL-3-treated mice injected with
      anti-CD4 mAb. These results suggest that IL-3 might play a role as Th2 amplifier
      in immune response to parasite infection.

PMID- 9784658
TI  - Effects of intracellular cyclic AMP modulators on human eosinophil survival,
      degranulation and CD11b expression.
AB  - BACKGROUND: Brochial asthma is characterized by infiltration of inflammatory
      cells such as lymphocytes and eosinophils. Theophylline is one of the most widely
      used drugs in the therapy of bronchial asthma, and phosphodiesterase (PDE)
      inhibition is thought to be an important mechanism of its anti-inflammatory
      actions. However, the detailed effects of PDE inhibition on eosinophils still
      remain unclear. METHODS: Eosinophils in peripheral blood obtained from normal
      subjects and patients with mild off-season allergic rhinitis were purified using
      CD16 negative selection. The following effects of theophylline (nonselective PDE
      inhibitor), KF19514 (selective PDE IV inhibitor), mirlinone (selective PDE III
      inhibitor), procaterol (beta2-adrenoceptor agonist) and N6, 2'-O
      dibutyryladenosine 3'5'-cyclic monophosphate (dB-cAMP; AMP analogue) on
      eosinophils were examined: (1) survival in the presence of interleukin-5, (2)
      degranulation by granulocyte/macrophage colony-stimulating factor (GM-CSF) or
      platelet-activating factor (PAF), (3) CD11b expression under GM-CSF or PAF
      stimulation and (4) intracellular cAMP level. RESULTS: Eosinophil survival was
      inhibited by theophilline, KF19514 or procaterol. GM-CSF- or PAF-induced
      degranulation was inhibited by theophylline, KF19514, procaterol or dB-cAMP.
      CD11b up-regulation by PAF was inhibited by theophylline, KF19514 or dB-cAMP,
      while GM-CSF-stimulated CD11b up-regulation was not significantly inhibited by
      any of the drugs tested. The levels of intracellular cAMP were increased by
      theophylline, KF19514 and procaterol. CONCLUSIONS: Intracellular cAMP is an
      important factor in the regulation of eosinophil biological functions. PDE IV
      inhibitors and beta2-agonists are suggested to be useful for the treatment of
      bronchial asthma through inhibition of eosinophil effector function.

PMID- 9784659
TI  - Bronchial hyperresponsiveness, hypersensitivity to analgesics and urinary
      leukotriene E4 excretion in patients with aspirin-intolerant asthma.
AB  - This study was designed to investigate the protective effect of cromolyn sodium
      on airway sensitivity to sulpyrine, and bronchial responsiveness to methacholine,
      and to investigate whether this protective activity is associated with reduction
      in aspirin-induced excretion of urinary leukotriene E4 (u-LTE4), a marker of the
      cysteinyl LT overproduction that participates in the pathogenesis of aspirin
      induced asthma. We assessed the effects of pretreatment with cromolyn sodium on
      bronchoconstriction precipitated by inhalation of methacholine and sulpyrine in
      16 adult patients with mild or moderate aspirin-intolerant asthma; those who were
      in stable clinical condition and were hypersensitive to a sulpyrine provocation
      test were included in this study. A double-blind, randomized, crossover design
      was used. u-LTE4 was measured using combined reverse-phase high-performance
      liquid chromatography enzyme immunoassay. Cromolyn sodium protected against
      analgesic-induced bronchoconstriction through mechanisms that are not related to
      its bronchodilator property, but to the improvement of both bronchial
      hyperresponsiveness and hypersensitivity to analgesics (p<0.01 and p<0.001).
      Although excretion of u-LTE4 did not increase after the methacholine provocation
      test, it significantly increased after sulpyrine provocation (p<0.01).
      Furthermore, after pretreatment with cromolyn sodium, the maximum level of u-LTE4
      after the sulpyrine provocation test was significantly lower than in controls
      (p<0.01). These results support the hypothesis that cysteinyl LT is one of the
      most important components in the pathogenesis of aspirin-intolerant asthma.
      Cromolyn sodium improves both hypersensitivity to analgesics, and bronchial
      hyperresponsiveness in aspirin-intolerant asthma.

PMID- 9784660
TI  - Lack of cross-reactivity between casein and gliadin in sera from coeliac disease
      patients.
AB  - BACKGROUND: While searching for antigliadin and anticasein antibodies in sera
      from coeliac patients we investigated more than 20 persons suffering from this
      enteropathy. In some of sera, we registered antibodies against gliadin and in
      parallel the appearance of anticasein antibodies. A high percentage of glutamic
      acid has been proven by amino acid analysis in both these proteins. Therefore we
      try to demonstrate the existence of cross-reactivity between them in sera from
      coeliac patients. METHODS: We analyzed sera from 5 adult patients by using
      Western blot (SDS-PAGE and immunoblot assay). All of them had previously proven
      serum antibodies against casein and gliadin. In the procedure, antigliadin
      antibodies were removed from sera by adsorption with gliadin. Adsorbed antibodies
      were then eluted from the adsorbent. RESULTS: Adsorbed samples retained
      anticasein activity. Eluates had a strong reactivity to gliadin but not to
      casein. CONCLUSION: No cross-reactivity restricted to any of the immunoglobulin
      isotypes (IgG, IgM, IgA) had been proven between these two proteins. Before the
      final conclusion, we believe the study has to be completed by using partly of
      totally disassembled proteins by intestinal enzymes. It might be that enzymatic
      digestion could open some epitopes shared by both these proteins.

PMID- 9784661
TI  - Human parvovirus B19: prevalence of viral DNA in volunteer blood donors and
      clinical outcomes of transfusion recipients.
AB  - BACKGROUND AND OBJECTIVES: Blood donor units are not screened for human
      parvovirus B19 (B19) even though it can be acquired via blood products. We
      estimated the prevalence of B19 in a US volunteer blood donor population and
      determined the clinical outcomes of transfusion recipients. MATERIALS AND
      METHODS: Donor units were screened for B19 DNA by PCR, and positive units
      analyzed by EIA for B19 Ig. Unit usage was determined and recipient chart review
      conducted. RESULTS: B19 DNA was detected in 11/9, 568 allogeneic units (0.1%), of
      which 3 had no measurable B19 Ig. One individual developed anemia consistent with
      B19 infection after receiving a DNA+ unit lacking B19 Ig. CONCLUSIONS: The
      apparent low incidence of disease in patients transfused with B19 DNA+ components
      may be due to coexistence of neutralizing antibodies in donors and/or recipients.

PMID- 9784662
TI  - Clinical evaluation of transfusion of prestorage-leukoreduced apheresis
      platelets.
AB  - With increased use of platelet concentrate (PC) in recent years, adverse
      reactions to PC transfusion have received much clinical attention. Most of these
      reactions stem from white blood cells (WBC) contaminating the transfused PC.
      Several are thought to be preventable by removing WBC before PC storage. METHODS:
      We routinely filtered apheresis PC either during collection or immediately
      afterwards and monitored various indicators of platelet quality during storage.
      After transfusion to patients, transfusion efficacy and the type, severity, and
      frequency of posttransfusion side effects were compared with those of a control
      group in which PC was filtered at the bedside. RESULTS: Prestorage-filtered PC
      contained an average of 3.1+/-0.7 x 10(11) platelets and 0.9+/-1.2 x 10(6)
      contaminating leukocytes. Measurement of platelet function and metabolic
      indicators revealed normal values throughout the storage period. CD62 measurement
      revealed no undue platelet activation after filtration or during the storage
      period. Cytokine, histamine, bradykinin, and complement levels showed no
      significant increase after filtration or during storage. Transfusion efficacy and
      overall side effect incidence rates were similar for the prestorage- and bedside
      filtered groups, but reactions of the bedside-filtered group included serious
      reactions such as breathing difficulties and shock. No serious reactions were
      noted in the prestorage-filtered group. CONCLUSION: Filtering PC before storage
      has no adverse effect on PC quality and may reduce the severity of post
      transfusion side effects.

PMID- 9784663
TI  - Monocyte activation in platelet concentrates.
AB  - BACKGROUND AND OBJECTIVES: Cytokines in platelet concentrates contribute to
      febrile transfusion reactions. Activated monocytes are a major source of
      inflammatory cytokines, however the role of monocytes in cytokine production in
      platelet concentrates has not been clarified. This study undertook to quantitate
      monocytes, determine whether monocyte activation occurs and identify an
      association with IL-6 and IL-1beta concentrations in platelet concentrates.
      MATERIALS AND METHODS: 17 platelet concentrates were analysed for total leucocyte
      and monocyte counts, CD14 and CD16 monocyte-associated antigen expression and IL
      1beta and IL-6 measurements on days 1, 2, 3, 4 and 5. RESULTS: Monocytes in all
      platelet concentrates expressed increased levels of CD14 and CD16 from day 1 of
      storage. 10/17 platelet concentrates had elevated IL-6 levels by day 3. Platelet
      concentrates with IL-6 levels above 15 pg/ml on day 5 had monocyte counts between
      0.14 and 15.6 x 10(6)/unit on day 1, while those with IL-6 levels below 15 pg/ml
      had low monocyte counts of < 0.01 to 1.2 x 10(6)/unit on day 1. CONCLUSION:
      Monocytes present in platelet concentrates exhibit features of activation.
      Monocyte activation is present following the preparation of platelet
      concentrates, implicating the manufacturing process in its development. Increased
      IL-6 and IL-1beta levels during platelet concentrate storage are commonly
      associated with a higher monocyte count. However, no direct association could be
      identified between the extent of monocyte activation and the level of cytokine
      release.

PMID- 9784665
TI  - Does hyperconcentration result in platelet activation?. A flow-cytometric study
      of hyperconcentrated random donor platelets.
AB  - BACKGROUND AND OBJECTIVES: Hyperconcentration of platelets may lead to platelet
      activation and loss of platelet function. MATERIALS AND METHODS: Platelet
      activation following hyperconcentration was assessed using flow-cytometric
      detection of platelet P-selectin expression and platelet swirling. RESULTS:
      Platelet hyperconcentration led to a minimal increase in P-selectin expression
      and no difference in platelet swirling. CONCLUSION: Hyperconcentration was not
      associated with a clinically significant change in platelet activation and had no
      significant effect on platelet quality as detected by pH and platelet yield.

PMID- 9784664
TI  - Prevention of cytokine accumulation in platelets obtained with the COBE spectra
      apheresis system.
AB  - BACKGROUND AND OBJECTIVES: Febrile nonhemolytic transfusion reactions frequently
      accompany platelet transfusions and may be due to accumulation of cytokines
      mediating inflammation during storage of platelet concentrates (PCs). We wished
      to determine whether PCs collected using the COBE(R) SpectraTM Apheresis System
      (Version 4) were sufficiently leukocyte reduced (LR) to limit cytokine
      accumulation during storage. MATERIALS AND METHODS: Cytokine accumulation -
      interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha) - and
      release of platelet alpha-granule - P-selectin, transforming growth factor-beta1
      (TGF-beta1), platelet-derived growth factor AB (PDGF-AB), von Willebrand factor
      (vWf) - or dense granule (serotonin) markers were investigated during a 7-day
      storage period comparing apheresis-collected, LR PCs (LR PCs) and random donor
      platelets prepared from whole blood (WB). RESULTS: Leukocyte counts were reduced
      99.95% comparing LR PCs (5.7 x 10(5)/l) and WB PCs (1.09 x 10(9)/l). Little or no
      accumulation of leukocyte-derived cytokines was observed in LR PCs during storage
      in contrast to WB PCs. A reduction in the release of platelet alpha-granule
      proteins, such as P-selectin, TGF-beta1 and PDGF-AB, was observed on day 0 for LR
      PCs compared to WB PCs with little or no difference observed from day 3 to 7.
      Plasma vWf levels were higher in LR PCs compared to WB PCs on days 0-7.
      CONCLUSION: Leukocyte levels in PCs collected with the COBE Spectra Apheresis
      System are sufficiently low to limit cytokine production during 7 days of
      storage.

PMID- 9784666
TI  - Erythropoiesis in patients stimulated with erythropoietin: the relevance of
      storage iron.
AB  - BACKGROUND AND OBJECTIVES: The clinical importance of iron-restricted
      erythropoiesis in erythropoietin (EPO)-stimulated patients is controversial.
      MATERIALS AND METHODS: We therefore reviewed 70 patients randomized into clinical
      trials of aggressive autologous donation and oral iron supplementation, with or
      without recombinant human EPO therapy. RESULTS: Nineteen (27%) iron-depleted
      patients produced 5.4+/-2.8 ml RBC/kg compared to 4.8+/-2.3 ml RBC/kg
      (nonsignificant) in iron-replete patients due to endogenous EPO (placebo group)
      stimulation. EPO-treated iron-depleted patients produced 20% less RBC than iron
      replete patients (8.23+/-3.3 vs. 10. 2+/-4.0, p = 0.066). RBC volume expansion
      correlated with initial storage iron only in iron-replete patients who received
      EPO therapy. CONCLUSION: Initial storage iron status is a marginally important
      limitation to EPO-mediated erythropoiesis in the setting of oral iron
      supplementation. Strategies to maintain plasma transferrin saturation with
      intravenous iron therapy may be desirable to improve the erythropoietic response
      to EPO in this setting.

PMID- 9784667
TI  - c-fos and c-jun mRNA expression in activated cord and adult lymphocytes: an
      analysis by Northern hybridization.
AB  - BACKGROUND AND OBJECTIVES: To further analyze the neonatal immune response to an
      antigenic challenge such as blood transfusion, c-fos and c-jun mRNA expression
      were analyzed in twelve in-vitro-stimulated normal cord blood and ten in-vitro
      stimulated normal adult peripheral blood lymphocyte samples. MATERIALS AND
      METHODS: Lymphocyte samples were stimulated by either the mitogen
      phytohemagglutinin (PHA) or the monoclonal antibody alphaCD3. Proliferation rate
      and Northern blot hybridization were employed. RESULTS: Cord lymphocytes revealed
      a greater proliferation rate with PHA and alphaCD3 than adult lymphocytes (p =
      0.0081 and 0.0023, respectively). In addition, Northern blot analysis of cord and
      adult samples revealed similar maximal increases in c-fos (99+/-15 and 126+/-11%,
      p = 0.0126) and c-jun (123+/-9 and 185+/-38%, p = 0.0291) mRNA expression,
      respectively, as early as 15 min post-alphaCD3 stimulation. Adult lymphocytes
      showed an equivalent increase in mRNA expression of c-fos and c-jun (140+/-25 and
      155+/-31%) at 30 min post-PHA stimulation, while cord lymphocyte maximum c-fos
      and c-jun expression (82+/-6 and 142+/-12%) occurred at 15 min post-PHA
      stimulation (c-fos, p = 0.0354; c-jun, p = 0.0112). CONCLUSION: Although cord
      lymphocyte proliferation rates were significantly greater than those of adult
      lymphocytes following stimulation, lymphocyte activation, as analyzed by c-fos
      and c-jun mRNA expression, appears similar in both cord and adult samples. We
      conclude that cord lymphocyte activation exhibits an adult-type profile.

PMID- 9784668
TI  - Decrease in the concentration of vitamin E in blood and tissues caused by di(2
      ethylhexyl) phthalate, a commonly used plasticizer in blood storage bags and
      medical tubing.
AB  - BACKGROUND AND OBJECTIVES: Significant amounts of di(2-ethylhexyl) phthlate
      (DEHP) leach into blood stored in DEHP-plasticized PVC bags. The aim of this
      study was to find out whether DEHP at these low levels has any effect on the
      concentration of vitamin E, an antioxidant which affords protection against free
      radical damage. MATERIALS AND METHODS: DEHP was administered in low doses (150
      750 microg/100 g body weight) to rats intraperitoneally and the concentration of
      vitamin E in the liver and testes was measured. Concentration of vitamin E was
      also measured in blood stored in glass bottles in the presence and absence of
      DEHP and in blood stored in DEHP-plasticized PVC bags. RESULTS: A decrease in the
      concentration of vitamin E was observed in all cases. Administration of vitamin E
      to rats and incorporation of vitamin E in the additive solution in the case of
      blood prevented this decrease. CONCLUSION: DEHP even at very low doses caused a
      decrease in the concentration of vitamin E in liver and tests of rats given this
      substance. Blood stored in DEHP-plasticized bags also showed a decrease in the
      concentration of vitamin E.

PMID- 9784669
TI  - Blood transfusion at delivery and risk of subsequent malignant lymphoma in the
      mother.
AB  - BACKGROUND AND OBJECTIVES: Blood transfusion has been shown to be a risk factor
      for non-Hodgkin's lymphoma (NHL). MATERIALS AND METHODS: In a cohort of 77,928
      women with bleeding complications at delivery in the period of 1973-1986,
      subsequent NHL cases were identified and the number was compared with the number
      expected from national incidence rates. In a case-control study the proportion of
      transfused NHL cases was compared with the proportion of transfused controls.
      RESULTS: The observed number of NHL in the cohort was 18 versus 22.0 expected.
      Information on transfusion was obtained for 15 of the NHL cases and none (0%) was
      transfused versus 32 out of 136 controls (23%). CONCLUSIONS: Blood transfusion at
      delivery is not a risk factor for NHL. The immune tolerance induced by pregnancy
      may reduce the risk of NHL associated with the transfusion of allogeneic blood
      cells.

PMID- 9784670
TI  - Intrapatient comparison of an intermittent and a continuous flow cell separator
      for the collection of progenitor and stem cells from the blood.
AB  - BACKGROUND AND OBJECTIVES: Continuous-flow and intermittent-flow blood cell
      separators (CFCS and IFCS) are both used to collect stem cells from the blood to
      rescue patients undergoing myeloablative treatment for cancer. MATERIALS AND
      METHODS: We designed a study to compare the collection efficiency of the two
      systems. The continuous-flow Cobe Spectra and the intermittent-flow Haemonetics
      MCS-3P were used to collect cells on consecutive days from 9 patients mobilised
      with G-CSF with or without chemotherapy. Blood obtained before leukapheresis and
      the leukapheresis product were analysed for their content of red and white cells,
      platelets, CD34-positive cells, GM-CFC, CFC-E, and BFU-E. An extraction ratio was
      calculated. RESULTS: We found that the CFCS extracted about 4 times more
      mononuclear cells per unit time, 3 times more CD34-positive, and 4 times more
      clonogenic cells than the IFCS. The subject acceptability of the two systems was
      similar. CONCLUSION: The CFCS is a more efficient system for stem cell
      collection. IFCS requires a longer harvesting time for the same result.

PMID- 9784671
TI  - Prevalence of antibodies to HTLV-I/II in blood donors and risk populations in
      South China.

PMID- 9784673
TI  - Consensus conference on platelet transfusion: final statement.

PMID- 9784672
TI  - Use of cord blood progenitor cells as an alternative for bone marrow
      transplantation.

PMID- 9784674
TI  - [1998 malaria therapy].
AB  - A review of the principal antimalarial drugs is presented as the basis for
      specific recommendations on the treatment of malaria. These are adapted to
      conditions in Switzerland. Considering that the majority of Plasmodium falciparum
      infections imported into this country are acquired in areas with a high
      prevalence of chloroquine resistance, mefloquine is generally considered the
      first-line drug for the treatment of uncomplicated falciparum malaria. For severe
      tropical malaria, or if parasitaemia exceeds 2%, quinine remains the drug of
      choice. The pharmacological decision must estimate the risk of drug-resistant
      malaria and consider the clinical condition, possible intolerance and drug
      interactions. Prognosis is always difficult in falciparum malaria; hence
      hospitalization is always strongly recommended if the course is in doubt and if
      close monitoring of the patient is not otherwise guaranteed. In hospital,
      ancillary treatment (e.g. exchange transfusion) must receive timely
      consideration. Special considerations must be borne in mind with regard to the
      treatment of malaria in children and during pregnancy.

PMID- 9784675
TI  - [Comparison of ambulatory and inpatient treatment of acute deep venous thrombosis
      of the leg: subjective and economic aspects].
AB  - The frequency of clinical recurrence and pulmonary embolism in patients with
      acute deep venous thrombosis is reduced to the same extent by hospital treatment
      (with unfractionated heparin) as by treatment at home (with low-molecular-weight
      heparin). Very few data on subjective parameters of effectiveness have been
      published. We performed a prospective randomized trial comparing outpatient with
      in-hospital treatment in 28 patients. Six clinical and quality-of-life related
      parameters of effectiveness were assessed quantitatively: clinical course (with a
      score system), pain of venous congestion of the calf muscles (with Lowenberg's
      test), subjective perception of pain and general well-being (with visual analogue
      scales), satisfaction with the care provided, and absence from work. Subjective
      effectiveness was compared with the costs of each form of treatment. Outpatient
      treatment was significantly more effective than in-hospital treatment with regard
      to the objective parameters. It was, however, associated with less well-being and
      more pain than in-hospital treatment. The discrepancy is explained by eventually
      insufficient adjuvant treatment measures (which consisted of external leg
      compression by stockings and forced walking) and by anxiety brought on by the
      information that potentially lethal pulmonary embolism could occur despite
      anticoagulant therapy. Outpatient treatment was less costly. On the average and
      per patient it was CHF 3944 less expensive than treatment in hospital. An
      estimation reveals that the Swiss health care system would save about CHF 25
      million per year if the 85% of patients with deep-vein thrombosis suitable for
      home care were given this form of treatment. We conclude that outpatient
      management is subjectively cost-effective but should be optimised to eliminate
      certain drawbacks associated with it.

PMID- 9784676
TI  - [Post-mortem evaluation following oncologic treatment of the functional and
      bacteriologic status of 25 permanent venous access devices].
AB  - Permanent venous access devices allow long-term parenteral treatment under
      relatively safe and comfortable conditions. Nevertheless, this use is associated
      with some degree of (particularly infectious) morbidity. 25 permanent access
      devices were removed surgically in immediate autopsies and cultured. Some half
      were infected, with a clear prevalence (40%) for Staphylococcus coagulase
      negative. The results were related to clinical history and compared with the
      figures and conclusions of other studies. It is proposed that in certain
      situations cultures of native blood should be carried out more frequently through
      the permanent venous access, with a view to possible specific targeted antibiotic
      therapy associated with the heparinized lock.

PMID- 9784678
TI  - [Bothersome, posture-dependent cough. Tracheopathica osteochondroplastica].

PMID- 9784677
TI  - [Septic pylephlebitis with detection of gas in the portal vein: a rare
      complication of sigmoid diverticulitis].
AB  - Pylephlebitis, septic thrombosis of the portal vein and its branches, is an
      infrequent complication of intra-abdominal inflammatory processes which may lead
      to thrombosis of the portal vein or to liver abscesses. Air in the protal venous
      system usually predicts a fatal outcome. The survival rate calculated in all
      reported cases is less than 25%. It is important to detect portal venous gas
      early. In detection of portal venous gas, ultrasound and computed tomography are
      more sensitive than plain radiographs. Pylephlebitis used to be a dreaded
      complication of appendicitis, but the incidence of this disease has greatly
      declined since the development of antibiotics and modern surgical techniques. We
      present two cases of pylephlebitis associated with gas in the portal vein as a
      result of left colonic diverticulitis treated by bowel resection. In spite of the
      occurrence of portal venous gas, the outcome may be favourable if this disease
      undergoes prompt surgical treatment.

PMID- 9784679
TI  - [Quality: when work turns into art].

PMID- 9784680
TI  - [Physical effects of cancer and its treatment: reconciliation with the damaged
      body image].

PMID- 9784681
TI  - [Postoperative pain treatment. The patient is the measure of all (pain-related)
      things].

PMID- 9784682
TI  - [Quality of care from the patient's point of view. Was the care first rate?].

PMID- 9784683
TI  - [The clinch between private sphere and the necessities of care].

PMID- 9784684
TI  - [A group project. Care of the student in his practice].

PMID- 9784685
TI  - [Role of the health nurse for future professionals. An approach to health via
      one's own personal resources].

PMID- 9784686
TI  - [Trip diary: 13 years of service with REGA. A flight nurse reports].

PMID- 9784687
TI  - [Call systems. Why patients ring so rarely].

PMID- 9784688
TI  - [Study of candidates for nursing education. Selection: art or science?].

PMID- 9784689
TI  - [Tell me a story or ... how to allow one's emotions to be revealed].

PMID- 9784690
TI  - [The status and developmental outlook of the priority scientific trend in
      environmental protection].
AB  - Scientific researches carried out in the area of environmental sanitation are
      closely related to the principal lines of activity in industry and farming of
      Ukraine. The main task of research work is establishing principles, criteria and
      methods of comprehensive assessment of injury to health secondary to
      environmental contamination. With the purpose of identification of the real
      physical and chemical environmental factors load that human body experiences, an
      inventory has been made at the Ukrainian Scientific Research Centre for Hygiene
      of carcinogen sources, with the concept having been worked out of creation of the
      integrated system for control of safe NPS operation, and a concept proposed of
      genetic monitoring, and of state genetic load surveillance service in different
      regions of Ukraine, taking account of the degree of environmental pollution.

PMID- 9784691
TI  - [The characteristics of the lipid peroxidation status and the activity of the
      main antioxidative enzymes in patients with duodenal peptic ulcer who took part
      in the cleanup of the aftermath of the accident at the Chernobyl Atomic Electric
      Power Station].
AB  - Results are submitted of investigations designed to study processes of lipid
      peroxidation and activity of chief antioxidant enzymes in those patients with
      duodenal ulcer who took part in the elimination of the effects of the Chernobyl
      accident. The above contingent of examinees displayed activation of lipid
      peroxidation (accumulation of conjugated dienes, keto-dienes, malonic dialdehyde)
      and decline in the activity of superoxide-dismutase, catalase. The results
      obtained attest to the need for using antioxidants in a complex therapy of
      patients with peptic ulcer, who have come to be exposed to ionizing radiation.

PMID- 9784693
TI  - [The characteristics of the lesions of the esophagogastroduodenal area in
      patients with chronic glomerulonephritis who have experienced the effect of
      ionizing radiation].
AB  - Clinical features were studied of the esophago gastroduodenal zone lesions in 136
      patients with chronic glomerulonephritis. The occurrence of the above lesions was
      found out to appreciably affect the clinical symptomatology and the course of the
      underlying disease in those persons who have come to be exposed to ionizing
      radiation. It is necessary that pathogenetic factors be taken into consideration,
      such as internal irradiation, bodily intoxication with nitrogenous constituents,
      disturbed microcirculation and motor-and-evacuatory function of the alimentary
      canal in order that we might prognosticate the course of the disease and choose
      the relevant mode of treatment.

PMID- 9784692
TI  - [The cytogenetic indices of participants in the cleanup of the aftermath of the
      accident at the Chernobyl Atomic Electric Power Station and their correction].
AB  - An analysis was performed of cytogenetic homeostasis in liquidators of the
      Chernobyl accident after-effects, which led to the belief that if the above
      contingent of subjects continue living in large industrial regions characterized
      by high levels of environmental contamination with industrial waste, such as that
      formed in the chemical, by-product coke, and metallurgical industries, they will
      not dispel disorders of the cytogenetic homeostasis (chromosomal and chromatic
      aberrations), which fact is believed to be due to the inhibition of the processes
      of elimination of somatic cells with a faulty genotype. Proposed for the
      correction of cytogenetic disorders are such options as a complex of antioxidants
      and intravascular laser irradiation of blood, that will, we believe, help in
      restoring the cytogenetic homeostasis.

PMID- 9784695
TI  - [Markers of death: biological age and the cytogenetic changes in the peripheral
      blood lymphocytes in older age groups].

PMID- 9784694
TI  - [The neurological and radiometric indices of those who worked in the cleanup who
      live on the territory of Chernigov Province].
AB  - The condition was studied as was the degree of neurologic changes in those
      persons who took part in the elimination of the aftereffects of the Chernobyl
      accident, with special reference to radiation pollution of the territory. Brain
      tissue of the deceased liquidators was found out to store 137Cs. The implication
      of the endogenous incorporation of radionuclides in the development of chronic
      radiation encephalopathy is discussed.

PMID- 9784697
TI  - [The current principles of the treatment of infectious myocarditis].

PMID- 9784696
TI  - [The clinical pharmacology of hypotensive agents. Angiotensin-converting enzyme
      inhibitors].

PMID- 9784698
TI  - [Endocrine organ function in chronic pancreatitis].

PMID- 9784700
TI  - [Melanoma of human skin: its epidemiology, etiology and pathogenesis].

PMID- 9784699
TI  - [The treatment of ischemic heart disease in patients with chronic kidney
      failure].

PMID- 9784701
TI  - [The role of crystalline lens lipids in the pathogenesis of age-related
      cataract].

PMID- 9784702
TI  - [The clinical course and cardiohemodynamic status of patients with different
      variants of diphtheritic myocarditis].
AB  - The clinical course was studied as was the condition of cardiohemodynamics in 126
      patients with different variants of diphtherial myocarditis (DM) versus 23
      patients with unspecific infectious and allergic myocarditis (UIAM). Early DM in
      the majority of cases runs a moderately severe or severe course because of a
      stronger--by comparison with late DM and UIAM--predisposition to cardiac
      insufficiency, sinus bradycardia and heart blocks as well as of a moderately
      severe systolic dysfunction of the left ventricle (LV), as evidenced by Echo-CG.
      Late DM runs, on the whole, a mild course, and is associated with minimal LV
      systolic function inadequacies.

PMID- 9784703
TI  - [The fatty acid composition of the lipids in the sweat of patients with
      complications in the acute period of a myocardial infarct].
AB  - Sweat lipids fatty acid (FA) composition was determined in patients presenting
      with uncomplicated course of acute myocardial infarction and in the development
      of pulmonary edema and pneumonia with the aid of a gas-chromatographic technique.
      The development in the patients of pulmonary complications was found out to be
      accompanied by a substantial elevation of sweat lipids content of polyunsaturated
      FA, linoleic and arachidonic FA in particular, which fact can be taken as a
      diagnostic and prognostic criterion.

PMID- 9784704
TI  - [The hormone level of the blood from the aorta and the coronary sinus in patients
      with ischemic heart disease under conditions of preoperative stress].
AB  - A total of 156 patients with ischemic heart disease were examined under
      conditions of preoperative stress in a multiple-modality study performed with the
      aid of such techniques as echocardiography involving calculation of the
      myocardial mass index, coronaroventriculography, measurements of the
      adrenocorticotrophic hormone, hydrocortisone, somatotrophic hormone,
      triiodothyronine and thyroxin in the blood from the coronary sinus and aorta. A
      conclusion has been reached that emotional strain influences myocardial
      hypertrophy. A possible significance of the studied hormonal indices is shown
      together with features thereof in IHD patients presenting with different degrees
      of left ventricular hypertrophy.

PMID- 9784705
TI  - [The risk of becoming infected with the hepatitis C virus in patients and medical
      workers in therapeutic institutions].
AB  - Sweat lipid fat-acid (FA) composition was measured with the aid of the gas
      chromatographic techniques in patients with non-complicated course of acute
      myocardial infarction as well as during the development of pulmonary edema and
      pneumonia. The latter processes were found out to be accompanied by a marked
      elevation of sweat lipids polyunsaturated FA, linoleic and arachidonic FA in
      particular, which fact may serve as an important diagnostic and prognostic
      criterion.

PMID- 9784706
TI  - [Central and regional hepatic hemodynamics in patients with ischemic heart
      disease and concomitant chronic persistent hepatitis].
AB  - The condition of hemorheology and hemodynamics has been studied in patients with
      exertional angina (n = 20) and with effort angina presenting with concomitant
      chronic persisting hepatitis (n = 25). Coronary patients presenting with
      concurrent abnormalities of the hepatobiliary system displayed a significant
      reduction in the hepatic bloodflow resultant from a long-duration disorder of the
      liver and association of disturbances in the central hemodynamics and local
      autoregulatory mechanisms of compensation for intraorganic circulation.

PMID- 9784707
TI  - [Helicobacter pylori and stomach cancer].
AB  - The neoplasms and gastric mucosa colonization with Helicobacter pylori was
      studied in 40 stomachs resected for expansive (n = 20) and infiltrative (n = 20)
      carcinoma using Giemsa staining histological sections, histochemical reactions to
      oxyreductase, and urease test. In expansive carcinoma of the stomach, H. pylori
      was identifiable both in the tumour and surrounding gastric mucosa in 70 per cent
      of cases; infiltrative carcinoma appeared to be associated with gastric mucosa H.
      pylori in 80 per cent, whereas tumour H. pylori were recordable in 30 per cent of
      cases, which fact is dependent upon the histological structure of carcinoma. The
      role H. pylori plays in cancerogenesis is discussed.

PMID- 9784708
TI  - [The pathomorphology and pathogenesis of lithium-induced nephropathy].
AB  - Results are submitted for a morphologic study of two nephrobiopsies in patients
      with manic-depressive psychosis on long-term treatment with lithium drugs, who
      developed clinical symptoms of chronic renal insufficiency. Light-optic,
      electronic-, and immunofluorescent microscopy was made use of in the study. Both
      biopsies showed features consistent with the diagnosis of chronic interstitial
      nephritis with manifest changes in proximal convoluted tubules of the kidney. On
      the basis of the morphologic picture of the kidney lesion and chemical nature of
      lithium (metal of the group and ionic identity with sodium and potassium) a
      conclusion was drawn that the initial mechanism in the development of renal
      pathology in exposure to lithium is a damage to the proximal convoluted tubules.

PMID- 9784710
TI  - [Structural-functional interrelations in patients with an epileptic syndrome in
      posttraumatic hydrocephalus].
AB  - Overall forty two patients presenting with epileptic syndrome in posttraumatic
      hydrocephalus in the remote period of light closed craniocerebral injury, who
      ranged from 16 to 60 years old, were examined. Degree of severity and variety of
      posttraumatic hydrocephalus were assessed by findings from axial computerized
      tomography, pneumoecephalography, magnetoresonance tomography. All patients
      underwent electroencephalography. The examinees were predominantly those persons
      presenting with light and internal symmetrical hydrocephalus. 57.2% of patients
      developed cerebral seizures within the first 5 years of sustaining the injury.
      Normal EEG was recordable in those patients with epileptic syndrome presenting
      with light and internal symmetrical hydrocephalus. Apparent diffusive
      disturbances in the bioelectrical activity of the brain were more common in
      moderately severe hydrocephalus and in mixed hydrocephalus. The presence of
      paroxysmal activity is a particular characteristic of patients with epileptic
      syndrome in outer hydrocephalus. A distinguishing feature of internal
      asymmetrical hydrocephalus is an observation of a decrease in the general level
      of biopotentials.

PMID- 9784709
TI  - [Histochemical changes in the level of insulin in the erythrocytes and of glucose
      in the blood in the most acute phase of ischemic stroke].
AB  - With the purpose of studying abnormalities of carbohydrate metabolism in the
      acutest phase of ischemic insult we examined 39 patients within the first 10 days
      of the development of ischemic insult in cerebral atherosclerosis (30 patients)
      and hypertensive disease (9 patients) before and 60, 90 and 120 min after the
      peroral administration of 50 g of glucose or subcutaneous administration of 5 U
      of insulin using the histochemical method of identification of insulin in
      erythrocytes together with the biochemical method of measuring blood glucose. The
      degree of abnormalities of carbohydrate metabolism in such patients was found out
      to be dependent on the nosological form of the illness, severity of its course,
      and extent of affection of the brain.

PMID- 9784711
TI  - [Changes in the indices of cellular and humoral immunity in patients with
      infantile cerebral palsy].

PMID- 9784712
TI  - [Local humoral immunity in women with combined forms of infertility].
AB  - An evaluation was done of the immunity status in 100 women presenting with
      infertility of associated genesis. An immunologic investigation into blood serum,
      follicular fluid (FF) and peritoneal fluid (PF) was carried out at day 14-16 and
      18-23 of the menstrual cycle. The functional status of spermatozoa was
      characterized with the aid of the index of their survival in FF and PF. Local
      humoral immunity of FF and PF differs from the indices in blood serum, which fact
      was manifested by a striking reduction of Igs G, A, M. Sperm-immobilizing
      antibodies (SIAB) have been identified in blood serum, FF, and PF in 14, 4%,
      22.4%, and 25% of women. SIAB production is associated with inadequacy of local
      immunity, such as low levels of SIgA, IgA, and lysozyme. Occurrence of SIAB in PF
      and FF worsens general motility of spermatozoa by agglutination of the latter,
      which fact undoubtedly affects conception.

PMID- 9784713
TI  - [A lipid metabolic disorder in diabetics].
AB  - A total of 52 patients with diabetes mellitus (DM) who ranged from 15 to 60 years
      old were examined. Of these, 44 had type I DM, eight patients were afflicted with
      type 2 DM. 77 percent of the examinees were found out to develop
      hyperlipoproteinemia (HLP), with type 2b HLP having been diagnosed in 80 percent
      of the patients, type 4 HLP in 20 percent. The latter abnormality was seen in
      that group of patients presenting with a severe course of diabetes. In patients
      with type 1 DM HLP was not age-associated; it was developing in the presence of
      non-compensated carbohydrate metabolism, with duration of diabetes aggravating
      the severity of HLP. Type 2 DM patients revealed type 2b HLP with metabolic
      compensation being unsatisfactory. The above study suggests that lipid metabolism
      may be caused to return to normal by correction of carbohydrate metabolism, and
      leads to the belief that treatment of HLP is a worth-while exercise.

PMID- 9784714
TI  - [The importance of electrogastrography in clinical practice].
AB  - Changes were analyzed in electrogastrogrammes (EGG) of 135 patients who had
      underwent a surgical treatment for gastric and duodenal ulcer. Time of
      restoration of bioelectrical activity of the stomach was determined, with
      diagnostic and prognostic value of EGG during the process of rehabilitation being
      shown. Changes in EGG were studied in 92 patients with acute appendicitis.
      Efficiency of the above procedure was established with respect to obtaining
      supplementary objective data of informative value on the course of the
      pathological process in the abdominal cavity, which fact permits the
      prognostication of the different complications development. Transcutaneous
      electrostimulation of the stomach was shown to be helpful in gastroenterological
      patients as was intracavitary pneumomassage.

PMID- 9784715
TI  - [The synthetic leu-enkephalin--dalargin--in the therapy of the irritable bowel
      syndrome and chronic noninfectious undefined colitis].
AB  - The author proceeds from the belief that it is the dystrophic changes and
      disturbances in the regeneration of the intestinal epithelium that play a
      decisive role in the pathogenesis and morphogenesis of irritable intestinal
      syndrome and chronic non-infectious undefined colitis. The above alterations
      develop secondary to the action of harmful factors and disturbed trophic
      influences of neurohumoral systems of regulation during different stages of
      stress. At the same time the synthetic leu-enkefalin dalargin is endowed with a
      marked antistressor activity as well as ability to strikingly improve the
      regeneration of the epithelium. This was reason why therapeutic efficacy of
      dalargin has been given a trial in the above pathologies. Positive dynamics of
      symptoms of the conditions in question has been shown as well as of the
      histologic picture of colonic mucosa biopsies during the course of treatment of
      the above ailments with dalargin.

PMID- 9784716
TI  - [The diagnosis and surgical treatment of gastroduodenal ulcers combined with
      chronic cholecystitis].

PMID- 9784717
TI  - [The clinico-genetic characteristics of the origin and manifestation of
      colorectal cancer].
AB  - A clinical and genealogical investigation has been carried out in 169 subjects of
      both sexes, presenting with colorectal oncopathology. Particular features of the
      colorectal carcinoma in the patients have been recognized. The frequency of the
      tumours spread in the relatives of the probands is determined as is the spectrum
      of aggregation of large intestine carcinoma with neoplasia of other genesis in
      the pedigrees. The data obtained suggest an important contribution of genetic
      factors into the origination of colorectal carcinoma.

PMID- 9784718
TI  - [The long-term use of corticosteroid inhalations in bronchial asthma patients].
AB  - Our objective in this study was to observe how prolonged exposure to high doses
      of inhalation and peroral corticosteroids impacted on the risk of development of
      posterior subcapsular cataract (PSC). Of the 48 examinees, 27 percent revealed
      PSC. The presence of PSC correlated with diurnal dose of prednisone as well as
      with duration of its administration but no correlation was found between PSC and
      inhalation corticosteroids. The data obtained suggest to us that inhalation
      corticosteroids in hormone-dependent patients with bronchial asthma reduce the
      risk of PSC development.

PMID- 9784719
TI  - [The objective criteria for the differential cytological diagnosis of small-cell
      undifferentiated lung cancer].

PMID- 9784720
TI  - [The efficacy of treatment with native lymphoblast alpha-interferon (Wellferon)
      in patients with chronic myeloleukemia].
AB  - Data are submitted on treatment with vellferon of patients with chronic myeloid
      leukemia (CML) in the chronic phase of the illness. The data obtained suggest
      that vellferon has a pronounced therapeutic effect in CML patients. The drug has
      a positive effect on both the clinical- and hematological status and cytogenetic
      changes in bone marrow cells. After 3-month treatment of patients with vellferon
      the sizes of the liver and spleen returned to normal as did the peripheral blood
      leucocyte and platelet counts. Two patients revealed a minimum cytogenetic
      response to therapy, one patient achieved a complete cytogenetic remission, and
      only 1 patient failed to demonstrate a cytogenetic response. A six-month therapy
      was associated with a complete clinical-and-hematological remission in 4 (80%)
      patients, with its duration ranging between 4 to 5 months, all patients
      maintaining a minimum cytogenetic response to vellferon treatment. Thus,
      treatment with vellferon permits obtaining not only a clinical and hematological
      but also a cytogenetical response to therapy in a major proportion of CML
      patients.

PMID- 9784721
TI  - [A new classification of the motor disorders in patients who have had a stoke].
AB  - A new classification is substantiated of motor syndromes in patients with
      hemispheric cerebral insult. The classification is represented by six syndromes,
      it takes advantage of the degree of upper and lower monoparesis, relation between
      the two, condition of muscular tone, ability of people to help themselves, to
      cope in their homes, and other items. Correctness of the classification has been
      confirmed by the method of correlation analysis and parameters of stimulation
      electromyography. The use of the classification will, we believe, help in
      administering the relevant rehabilitative therapy treatments in a more efficient
      way.

PMID- 9784723
TI  - [Radiation-induced intracranial meningiomas].
AB  - Based on the analysis of 112 cases a clinical characterization has been done of
      intracranial meningiomas developed secondary to X-ray irradiation of the head for
      fungus disease of skull integuments. X-ray irradiation increases the risk of
      intracranial meningioma development up to 4-fold. Radiation-induced intracranial
      meningiomas are characterized by particular features of clinical manifestations,
      by preponderance of hyperdense forms, by being of large size, as well as by a
      high frequency of changes in the adjacent bone presenting as hyperostosis,
      usuration, and destruction. The above meningiomas are notable for a high specific
      weight of anaplastic varieties.

PMID- 9784722
TI  - [Long-latency evoked potentials in response to rotational stimulation as an early
      method for the diagnosis of cochleovestibular disorders].
AB  - With the purpose of improving an early diagnosis of cochleovestibular
      disturbances in patients with acoustic neuritis of the vascular genesis caused by
      the brain major arteries pathologies, a new method was employed of long-latent
      evoked potentials in response to rotational stimulation (EPR). On the basis of
      the findings obtained it can be asserted that the injury to the internal ear is
      strongly related to alterations in the cortical region of the vestibular
      analyzer. EPR parameters are valuable differential-diagnostic criteria that
      reflect compensatory functional capabilities of cerebrum cortex in patients in
      different parts of their life.

PMID- 9784724
TI  - [Surgical treatment results in patients with severe forms of the carpal tunnel
      syndrome].
AB  - A retrospective and prospective study was undertaken to determine efficacy of
      carpal tunnel decompression in patients with advanced carpal tunnel syndrome
      (CTS). The criteria for inclusion in this study were clinical and nerve
      conduction studies (NCS). Between 1985-1991, 1511 NCSs performed were positive
      for CTS.

PMID- 9784725
TI  - [The efficacy of enterosorption and a combination of antioxidants in
      schizophrenics].
AB  - A total of 143 patients with schizophrenia, who ranged from 28 to 42 years old,
      were studied. Of these, 68 patients were running a continuously progredient
      course, 75 were in the phase of exacerbation of the attack-like progredient
      course of schizophrenia. Group I (n = 76) of patients received the enterosorbent
      polysorb and a complex of antioxidants (tocoferolum acetatum, ascorbic acid,
      quercetin) as a supplement to the conventional therapy, group II (n = 67) was
      placed on the conventional therapy only. A complex of the antioxidants as well as
      the enterosorbent had a positive effect on the clinical course of the condition
      in 63.2% of group I patients who managed, among other therapeutic benefits, to
      achieve a stable remission. They have also demonstrated a concomitant improvement
      or normalization of indices for lipid peroxidation.

PMID- 9784726
TI  - [The use of Spasmomen (otilonium bromide) in pediatrics].
AB  - Spasmomen is an affective medicinal substance for treating functional pathologies
      of digestive organs in children. The above drug is well tolerated, with no
      adverse events or complications being associated with its intake. Spasmomen as a
      drug having spasmolytic effect can be recommended for use in pediatric practice
      for treating children in all age brackets.

PMID- 9784728
TI  - [The functional status of the drivers of interurban buses under the combined
      action of adverse occupational factors].

PMID- 9784727
TI  - [The efficacy of using physical factors in patients with generalized
      periodontitis at a sanatorium-preventorium].
AB  - Kept under observation by the medical staff were 110 patients with mild or
      moderately severe generalized parodontitis in a sanatorium-preventorium setting.
      Depending on the severity of the process in the parodontium tissues the patients
      were given a differentiated treatment (mouth-baths with a chloridic-sodic mineral
      water, gum mud poultice applications, low frequency interference currents).
      Clinical, paraclinical, and laboratory methods were used to asses the studies
      results effectiveness. The greatest therapeutic benefit occurred in those
      patients who received a combined treatment with chloridic-sodic mineral water
      mouth-baths, gum mud poultice applications, and low frequency interference
      currents.

PMID- 9784729
TI  - [The working, life style and health conditions of welders (social hygiene
      research)].
AB  - An analysis was performed of results of a sociological investigation, which
      showed a greater specific weight among the examinees of welders of 20 to 49 years
      old (62.9%) who had a sufficiently long general and occupational service
      duration. Increase in the length of service was found to be associated with
      increased frequency of complaints related to function disorders of the nervous
      system, such as general weakness, an increased tendency to become fatigued,
      dyskinesia type motor impairment, irritability. Preventive examination of wedding
      operators showed the disorders of the cardiovascular system to prevail among
      them, with arterial hypertension being the most common morbidity. A major
      proportion of the examinees complained about feeling a pain in the heart region
      both in rest and exercise.

PMID- 9784730
TI  - [Functional changes in the subclinical stage of manganese toxicosis in miners].
AB  - Based on the study of 66 miners in the subclinical stage of manganotoxicosis the
      principle functional changes have been ascertained in the given condition.
      Revealed in the above series were an increased content of manganese in the hair
      of more than 3 mg% (95.5%-100.0%), the presence of neurosis-like condition
      presenting with elements of somatized depression, anxiety, asthenization, slight
      decline in the mnestic functions (69.6%-93.5%), mild impairment of the power of
      voluntary movement, parasympathetic type vegetative dystonia (42%-73.7%), slight
      changes in cerebral and peripheral hemodynamics (36.6%-68.6%), disordered
      bioelectrical activity of muscles of the extrapyramidal type (53.7%-83.2%),
      breakdown of mechanisms of adaptation of the sympathoadrenal (19.1%-49.3%) and
      cholinergic (26.3%-57.9%) systems.

PMID- 9784731
TI  - [A case of primary progressive multiple sclerosis in childhood].

PMID- 9784733
TI  - [The effect of combined laser and electropuncture on the bioelectrical potentials
      and skin temperature of patients with gastroesophageal reflux].
AB  - Biophysical processes were studied in biologically active points by recording
      bioelectrical potentials and skin temperature under exposure to a combined laser-
      and electropuncture. Use of laser- and electropuncture combined in treatment of
      patients with gastroesophageal reflux may have a positive effect on their skin
      bioelectrical potentials and condition of thermoregulation. Changes in
      biopotentials and skin temperature can provide an index of the functional state
      of the vegetative nervous system.

PMID- 9784732
TI  - [The efficacy of physiotherapeutic methods in the treatment of chronic
      pancreatitis taking into account the season of the year].
AB  - Overall thirty patients with chronic pancreatitis were studied for expediency of
      differentiated employment of physiotherapeutic procedures with season of the year
      being taken into consideration. Shown during the course of treatment was a high
      clinical efficiency of inhibition of the lipid peroxidation processes and
      activation of glutathione link of the antioxidant system of defence. Combined use
      of CMC and phonophoresis with solcoseril ointment and 10% methyluracil ointment
      makes for enhancement of general bodily resistance, promoting more prolonged
      remission.

PMID- 9784734
TI  - [The treatment of a flat condyloma on the cervix uteri by CO2-laser therapy].
AB  - Employed in the treatment of 102 female patients with flat condyloma of cervix
      uteri was a continuous-action CO2-laser. High efficiency of the above method has
      been demonstrated together with expediency of performing laser coagulation in the
      papilloma-virus infected zones as well as in the periphery of intact tissues. It
      is recommended that etiopathogenetic therapy be applied in the post-laser therapy
      period.

PMID- 9784735
TI  - [Ozone hemotherapy and the basal metabolic pathways of body adaptation in
      gestoses].
AB  - Changes in indices for the principle metabolic pathways of bodily adaptation in
      gestoses were studied as were potentialities of correction thereof with
      ozonohemotherapy. Revealed in particular was an indirect influence of OHT on
      glycolysis and gluconeogenesis together with a stimulatory action on the activity
      of the key enzyme of the pentosephosphatic pathway. Disturbances in the course of
      processes of glycolysis and gluconeogenesis in the organism of the gestoses
      patients warrant further study to work out options for a specific correction of
      intracellular metabolism in the given pathology and to prevent complications.

PMID- 9784736
TI  - [The efficacy of flower pollen in patients with rheumatoid arthritis and
      concomitant diseases of the gastroduodenal and hepatobiliary systems].
AB  - Kept under medical surveillance were 93 patients with rheumatoid arthritis (RA)
      of different degrees of activity, articular and visceral manifestations. Of
      these, 83 had apparent and latent afflictions of the gastroduodenal and
      hepatobiliary systems (gastritis, gastroduodenitis, peptic ulcer, cholecystitis,
      hepatitis). Floral pollen (FP) was used as a gastro- and hepatocytoprotectors. FP
      had a marked positive effect on disorders of the gastroduodenal and hepatobiliary
      systems and, to a lesser extent, on clinical manifestations and course of RA, as
      evidenced by clinical and biochemical, endoscopic, and ultrasonic investigations.

PMID- 9784737
TI  - [The formalized functional features of an automated system for managing the
      public health of an individual region].

PMID- 9784738
TI  - [The cause-and-effect validation of the definitions for a "state system of public
      health" and of a "public health for the population"].

PMID- 9784739
TI  - [The methodology and outlook for the development of medical affairs under current
      conditions].

PMID- 9784741
TI  - Red alert--biosensor identifies bacteria in the air.

PMID- 9784740
TI  - [Glomerulonephritis in the general medical statistical reporting of Ukraine].

PMID- 9784742
TI  - Sample preparation for LC/MS/MS: analyzing biological and environmental samples.

PMID- 9784743
TI  - Measurement of amide hydrogen exchange by MALDI-TOF mass spectrometry.
AB  - Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass
      spectrometry (MS) was used to determine amide proton/deuteron (H/D) exchange
      rates. The method has broad application to the study of protein conformation and
      folding and to the study of protein-ligand interactions and requires no
      modifications of the instrument. Amide protons were allowed to exchange with
      deuterons in buffered D2O at room temperature, pD 7.25. Exchanged deuterons were
      "frozen" in the exchanged state by quenching at pH 2.5, 0 degree C and analyzed
      by MALDI-TOF MS. The matrix mixture consisted of 5 mg/mL alpha-cyano-4
      hydroxycinnamic acid, acetonitrile, ethanol, and 0.1% TFA. The matrix was
      adjusted to pH 2.5, and the chilled MALDI target was rapidly dried. Deuteration
      of amide protons on cyclic AMP-dependent protein kinase was measured after short
      times of incubation in deuterium by pepsin protein digestion and MALDI-TOF MS
      analysis. The unseparated peptic digest was analyzed in a single spectrum of the
      mixture. From five spectra, H/D exchange rates were determined for some 40
      peptides covering 65% of the protein sequence.

PMID- 9784744
TI  - Routine DNA sequencing of 1000 bases in less than one hour by capillary
      electrophoresis with replaceable linear polyacrylamide solutions.
AB  - Long, accurate reads are an important factor for high-throughput de novo DNA
      sequencing. In previous work from this laboratory, a separation matrix of high
      weight-average molecular mass (HMM) linear polyacrylamide (LPA) at a
      concentration of 2% (w/w) was used to separate 1000 bases of DNA sequence in 80
      min with an accuracy close to 97% (Carrilho, E.; et al. Anal. Chem. 1996, 68,
      3305-3313). In the present work, significantly improved speed and sequencing
      accuracy have been achieved by further optimization of factors affecting
      electrophoretic separation and data processing. A replaceable matrix containing a
      mixture of 2.0% (w/w) HMM (9 MDa) and 0.5% (w/w) low-weight-average molecular
      mass (50 kDa) LPA was employed to enhance the separation of DNA sequencing
      fragments in CE. Experimental conditions, such as electric field strength and
      column temperature, as well as internal diameter of the capillary column, have
      been optimized for this mixed separation matrix. Under these conditions, in
      combination with energy-transfer (BigDye) dye-labeled primers for high signal-to
      noise ratio and a newly developed expert system for base calling, the
      electrophoretic separation of 1000 DNA sequencing fragments of both standard
      (M13mp18) and cloned single-stranded templates from human chromosome 17 could be
      routinely achieved in less than 55 min, with a base-calling accuracy between 98
      and 99%. Identical read length, accuracy, and migration time were achieved in
      more than 300 consecutive runs in a single column.

PMID- 9784745
TI  - Influence of the hapten design on the development of a competitive ELISA for the
      determination of the antifouling agent Irgarol 1051 at trace levels.
AB  - Enzyme-linked immunosorbent assays (ELISAs) with a high detectability have been
      developed for determination of the antifouling agent Irgarol 1051. The features
      of the resulting assays have been rationalized by using molecular mechanic
      calculations (MM2+) to correlate the chemical structure of different immunizing
      haptens and the corresponding avidities of the obtained antisera. The ability of
      Irgarol 1051 to compete for the antibody binding sites with 11 horseradish
      peroxidase enzyme tracers, differing in the chemical structures of the hapten,
      has been investigated. The present paper demonstrates that high-quality
      antibodies and, therefore, immunoassays reaching very low detection limits could
      be predicted by molecular modeling studies of the analyte conformations and of
      the immunizing haptens' geometries, hydrogen-bonding capabilities, and electronic
      distributions. Two of the ELISAs obtained have been optimized to obtain
      reproducible immunoassays. The dynamic ranges of both assays are between 30 and
      200 ng/L, and the limits of detection are approximately 16 ng/L. The reported
      immunoassays have been evaluated and validated by analyzing spiked and real
      seawater samples. Irgarol 1051 has been found to be present in two of the
      geographical locations analyzed at concentration levels dependent on the time of
      year. The analytical results obtained with these immunoassays have been validated
      by chromatographic methods.

PMID- 9784746
TI  - Sanger DNA-sequencing reactions performed in a solid-phase nanoreactor directly
      coupled to capillary gel electrophoresis.
AB  - A miniaturized, solid-phase nanoreactor was developed to prepare Sanger DNA
      sequencing ladders which was directly interfaced to a capillary gel
      electrophoresis system. A biotinylated fragment of the rat brain actin gene (1
      kbp) was amplified by PCR and attached to the interior wall of an
      (aminoalkyl)silane-derivatized fused-silica capillary tube via a
      biotin/streptavidin/biotin linkage. Coverage of the capillary wall with the
      biotinylated DNA averaged 77 +/- 10%. Stability of the anchored template under
      pressure (33 nL/s) and electroosmotic flows (11.3 nL/s) were favorable, requiring
      rinsing for > 150 h to reduce the surface coverage by only 50%. In addition, the
      immobilized template was stable toward temperatures required for preparing
      sequencing ladders, even under cycling conditions. Standard Sanger
      dideoxynucleotide termination performed in a large-volume (approximately 8
      microL) solid-phase reactor using the thermally stable polymerase enzymes Taq and
      Vent and the polymerases T7 and Bst with off-line slab gel electrophoresis and
      autoradiographic detection indicated that acceptable fragment generation was
      achieved only in the case of the thermally stable polymerases. Banding was not
      apparent for T7 and Bst since all reagents were inserted into the column in a
      single plug at the beginning of the reaction. A small volume reactor (volume
      approximately 62 nL) was then used to perform DNA polymerase reactions and was
      coupled directly to a capillary gel column for separation. The capillary reactor
      was placed inside a thermocycler to control the temperature during chain
      extension and was directly connected to the gel column via zero dead volume fused
      silica connectors. The complementary DNA fragments generated (C-track only) in
      the reactor were denatured using heat and directly injected onto the gel-filled
      capillary for size separation with detection accomplished using near-IR laser
      induced fluorescence. Extension and single-base separation resolution of the C
      track, which was directly injected onto the gel column, was estimated to be > 450
      bases from the primer annealing site with plate numbers ranging from 1 x 10(6) to
      2 x 10(6)/m.

PMID- 9784747
TI  - Automation and integration of multiplexed on-line sample preparation with
      capillary electrophoresis for high-throughput DNA sequencing.
AB  - An integrated and multiplexed on-line instrument starting from DNA templates to
      their primary sequences has been demonstrated based on multiplexed microfluidics
      and capillary array electrophoresis. The instrument automatically processes eight
      templates through reaction, purification, denaturation, preconcentration,
      injection, separation, and detection in a parallel fashion. A multiplexed
      freeze/thaw switching principle and a distribution network were utilized to
      manage flow and sample transportation. Dye-labeled terminator cycle-sequencing
      reactions are performed in an eight-capillary array in a hot-air thermal cycler.
      Subsequently, the sequencing ladders are directly loaded into separate size
      exclusion chromatographic columns operated at approximately 60 degrees C for
      purification. On-line denaturation and stacking injection for capillary
      electrophoresis is simultaneously accomplished at a cross assembly set at
      approximately 70 degrees C. Not only the separation capillary array but also the
      reaction capillary array and purification columns can be regenerated after every
      run. The raw data allow base calling up to 460 bp with an accuracy of 98%. The
      system is scalable to a 96-capillary array and will benefit not only high-speed,
      high-throughput DNA sequencing but also genetic typing.

PMID- 9784748
TI  - Purge-and-trap isothermal multicapillary gas chromatographic sample introduction
      accessory for speciation of mercury by microwave-induced plasma atomic emission
      spectrometry.
AB  - A compact device based on purge-and-trap multicapillary gas chromatography was
      developed for sensitive species-selective analysis of methylmercury and Hg2+ by
      atomic spectrometry. The operating mode includes in situ conversion of the
      analyte species to MeEtHg and HgEt2 and cryotrapping of the derivatives formed in
      a 0.53-mm-i.d. capillary, followed by their flash (< 30 s) isothermal low
      temperature separation on a minimulticapillary (22 cm) column. The very low
      detection limits obtained (0.01 pg mL-1 of Hg for methylmercury) are due to the
      narrow injection band and reduced peak broadening in a bundle of 0.038-mm
      capillaries at high flow rates (> 60 mL min-1) compatible with an MIP AES
      detector (no dilution with a makeup gas is required). Developments regarding each
      of the steps of the analytical procedure and effects of operational variables
      (sample volume, purge flow, trap temperature, separation conditions) are
      discussed. The device allows speciation of MeHg+ and Hg2+ down to 5 pg g-1 in
      urine and, after a rapid microwave-assisted hydrolysis, down to 0.1 ng g-1 in
      solid biological samples with a throughput of 6 samples/h. The analytical
      protocols developed were validated by the analysis of DORM-1 (dogfish muscle),
      TORT-1 (lobster hepatopancreas), and Seronorm urine certified reference
      materials.

PMID- 9784749
TI  - An ion funnel interface for improved ion focusing and sensitivity using
      electrospray ionization mass spectrometry.
AB  - To improve upon the already impressive sensitivity achievable with electrospray
      ionization sources, a novel electrohydrodynamic ion funnel interface has been
      developed and implemented with a triple-quadrupole mass spectrometer. The ion
      funnel interface effectively consists of a series of ring electrodes of
      increasingly small internal diameters to which rf and dc electric potentials are
      coapplied. In the 1-10-Torr pressure range, the electric fields cause the
      collisionally damped ions to be more effectively focused and transmitted as a
      collimated ion beam. This paper describes the ion funnel design and presents an
      evaluation of its performance using a triple-quadrupole mass spectrometer. Ion
      transmission and m/z discriminating parameters (resulting in both effective low-
      and high-m/z cutoffs) are presented based upon both ion current measurements and
      mass spectra. Electrospray ionization mass spectra of selected protein solutions
      demonstrated well over 1 order of magnitude increase in signal relative to that
      of the instrument operated in its standard (inlet capillary-skimmer)
      configuration under similar conditions. The present results suggest that it will
      be feasible to realize close to 100% ion transmission efficiency for analytically
      relevant ions through the electrospray ionization interface and into the mass
      analyzer.

PMID- 9784750
TI  - Quantitative polymerase chain reaction based on a dual-analyte chemiluminescence
      hybridization assay for target DNA and internal standard.
AB  - We have developed a dual-analyte chemiluminescence hybridization assay for
      quantitative polymerase chain reaction (PCR). The method allows simultaneous
      determination of both amplified target DNA and internal standard (IS) in the same
      reaction vessel. The target DNA from the sample (233 bp) was coamplified with a
      constant amount of a recombinant DNA IS that had the same size and primer binding
      regions as the target DNA, differing only by a 24-bp sequence, centrally located.
      Biotinylated PCR products from target DNA and IS were captured on a single
      microtiter well coated with streptavidin. The amplified target DNA was hybridized
      with a digoxigenin-labeled specific probe, and the hybrids were determined by
      using antidigoxigenin antibody labeled with aequorin. The amplified DNA IS was
      hybridized, in the same well, with a fluorescein-labeled probe, and the hybrids
      were determined by using an antifluorescein antibody conjugated to alkaline
      phosphatase. Aequorin was measured by adding a Ca(2+)-containing light-triggering
      solution. Alkaline phosphatase was measured by using a dioxetane chemiluminogenic
      substrate. The ratio of the luminescence values obtained from the target DNA and
      IS amplification products was linearly related to the number of target DNA
      molecules present in the sample prior to amplification. The linear range extended
      from 430 to 315,000 target DNA molecules. Average CVs ranged from 7 to 17%. The
      proposed system is expected to facilitate the automation and routine use of
      quantitative PCR.

PMID- 9784751
TI  - Biosensor for direct determination of organophosphate nerve agents using
      recombinant Escherichia coli with surface-expressed organophosphorus hydrolase.
      1. Potentiometric microbial electrode.
AB  - A potentiometric microbial biosensor for the direct measurement of
      organophosphate (OP) nerve agents was developed by modifying a pH electrode with
      an immobilized layer of Escherichia coli cells expressing organophosphorus
      hydrolase (OPH) on the cell surface. OPH catalyzes the hydrolysis of
      organophosporus pesticides to release protons, the concentration of which is
      proportional to the amount of hydrolyzed substrate. The sensor signal and
      response time were optimized with respect to the buffer pH, ionic concentration
      of buffer, temperature, and weight of cells immobilized using paraoxon as
      substrate. The best sensitivity and response time were obtained using a sensor
      constructed with 2.5 mg of cells and operating in pH 8.5, 1 mM HEPES buffer.
      Using these conditions, the biosensor was used to measure as low as 2 microM of
      paraoxon, methyl parathion, and diazinon. The biosensor had very good storage and
      multiple use stability. The use of cells with the metabolic enzyme expressed on
      cell surface as a biological transducer provides advantages of no resistances to
      mass transport of the analyte and product across the cell membrane and low cost
      due to elimination of enzyme purification, over the conventional microbial
      biosensors based on cells expressing enzyme intracellularly and enzyme-based
      sensors, respectively.

PMID- 9784752
TI  - Detection of heavy metal ions at femtomolar levels using protein-based
      biosensors.
AB  - Sensors based on proteins (GST-SmtA and MerR) with distinct binding sites for
      heavy metal ions were developed and characterized. A capacitive signal transducer
      was used to measure the conformational change following binding. The proteins
      were overexpressed in Escherichia coli, purified, and immobilized in different
      ways to a self-assembled thiol layer on a gold electrode placed as the working
      electrode in a potentiostatic arrangement in a flow analysis system. The
      selectivity and the sensitivity of the two protein-based biosensors were measured
      and compared for copper, cadmium, mercury, and zinc ions. The GST-SmtA electrodes
      displayed a broader selectivity (sensing all four heavy metal ions) compared with
      the MerR-based ones, which showed an accentuated selectivity for mercury ions.
      Metal ions could be detected with both electrode types down to femtomolar
      concentration. The upper measuring limits, presumably due to near saturation of
      the proteins' binding sites, were around 10(-10) M. Control electrodes similarly
      constructed but based on bovine serum albumin or urease did not yield any
      signals. The electrodes could be regenerated with EDTA and used for more than 2
      weeks with about 40% reduction in sensitivity.

PMID- 9784754
TI  - World Congresses of Gastroenterology. Vienna, Austria, September 6-11, 1998.

PMID- 9784753
TI  - Establishing a limit of recognition for a vapor sensor array.
AB  - Organic vapor analysis with microsensor arrays relies principally on two output
      parameters: the response pattern, which provides qualitative information, and the
      response sensitivity, which determines the limit of detection (LOD). The latter
      is used to define the operating limit in the low-concentration range, under the
      implicit assumption that, if a vapor can be detected, it can be identified and
      differentiated from other vapors on the basis of its response pattern. In this
      study, the performance of an array of four polymer-coated surface acoustic wave
      vapor sensors was explored using calibrated response data from 16 solvent vapors
      in Monte Carlo simulations coupled with pattern recognition analysis. The
      statistical modeling revealed that the ability to recognize a vapor from its
      response pattern decreases with decreasing vapor concentration, as expected, but
      also that the concentration at which errors in vapor recognition become excessive
      is well above the calculated LOD in most cases, despite the LOD being based on
      the least sensitive sensor in the array. These results suggest the adoption of a
      limit of recognition (LOR), defined as the concentration below which a vapor can
      no longer be reliably recognized from its response pattern, as an additional
      criterion for evaluating the performance of multisensor arrays. A generalized
      method for estimating the LOR is presented, as well as a means for improving the
      LOR via residual error analysis.

PMID- 9784755
TI  - 5th International Congress of the German Primate Society. Berlin, Germany,
      October 1-5, 1997. Abstracts.

PMID- 9784756
TI  - [Francophile meetings of digestive pathology. Paris, 21-25 March 1998.
      Abstracts].

PMID- 9784758
TI  - [Global status of medical imaging. II. Technical applications].

PMID- 9784757
TI  - [Global status of medical imaging. I. Clinical applications].

PMID- 9784759
TI  - American Society of Nephrology 31st annual meeting. Philadelphia, Pennsylvania,
      USA. October 25-28, 1998. Abstracts.

PMID- 9784760
TI  - Congress viewed with a scientist's critical eye.

PMID- 9784761
TI  - HCFA to tighten oversight of nursing home care; says drug use improved under OBRA
      '87 guidelines.

PMID- 9784762
TI  - Group begins work on indicators of quality medication use.

PMID- 9784763
TI  - Simple reminder can boost pneumococcal vaccination rates, say researchers.

PMID- 9784764
TI  - Incorrect dosage calculations by pediatric residents common, study shows.

PMID- 9784765
TI  - Administrative liability of pharmacy managers.

PMID- 9784766
TI  - Teaching patients about blood glucose meters.

PMID- 9784767
TI  - Celebrating ASHP's golden anniversary in best practices.

PMID- 9784768
TI  - Otitis media: focus on antimicrobial resistance and new treatment options.
AB  - Antimicrobial resistance among organisms that cause acute otitis media (AOM) and
      new approaches in the prevention and treatment of AOM are discussed. Organisms
      commonly responsible for causing AOM include Streptococcus pneumoniae,
      Haemophilus influenzae, and Moraxella catarrhalis. The evolution of pneumococcal
      resistance to penicillins, erythromycin, trimethoprim-sulfamethoxazole, and oral
      cephalosporins may require treatment with agents such as vancomycin or rifampin
      in certain patients. H. influenzae and M. catarrhalis are becoming increasingly
      resistant to penicillins, trimethoprim-sulfamethoxazole, oral cephalosporins, and
      macrolides. Mechanisms of resistance include changes in penicillin-binding
      proteins, production of beta-lactamase, alterations in target enzymes, and
      inhibition of drug access to the site of action. Because of changing resistance
      patterns and the limited spectra of activity of many currently available
      antimicrobials, new antimicrobials have been developed in the hope of improving
      therapy. While amoxicillin and trimethoprim-sulfamethoxazole are appropriate
      first-line agents, children at risk for resistant infections may be treated
      initially with cefuroxime axetil, cefpodoxime proxetil, cefprozil, or amoxicillin
      clavulanate. After local resistance patterns, patient adherence to therapy, in
      vitro data, and cost factors have been weighed, other agents to consider include
      loracarbef, clarithromycin, azithromycin, and ceftriaxone. Along with the efforts
      to improve treatment, research is focusing on the prevention of otitis media with
      bacterial and viral vaccines. The emergence of resistant strains of organisms
      causing AOM has complicated its treatment.

PMID- 9784770
TI  - Mail-in questionnaire for monitoring nausea and vomiting in oncology outpatients.
AB  - A patient questionnaire designed to help pharmacists monitor nausea and vomiting
      in outpatients receiving cancer chemotherapy was studied. A 12-item questionnaire
      was designed by combining items from the Morrow Assessment of Nausea and Emesis
      (MANE) and the Functional Living Index-Emesis (FLIE). Items included number of
      vomiting episodes, duration of nausea, number of antiemetics, severity of nausea
      and vomiting, impact on quality of life, and adverse effects. The questionnaire
      was printed on an addressed, postage-paid card. Over an eight-week period,
      outpatients in a hospital's oncology clinic were asked to complete the
      questionnaire at home during the three days after chemotherapy. Of 48 patients
      asked, 42 (88%) agreed to complete the questionnaire, and 36 (86%) of these
      patients mailed it back to the clinic. Of the respondents, 11 reported at least
      one episode of vomiting, and 22 reported nausea. Thirteen respondents logged
      nausea ratings of 3 or higher on a 7-point scale. Twenty respondents used
      antiemetics. Responses given by the patients in follow-up telephone interviews
      did not differ significantly from the responses collected with the questionnaire.
      More than 90% of patients who returned the questionnaire rated it as simple to
      complete. Pharmacists used the self-reports of nausea or vomiting in 7 (17%) of
      42 cases to recommend alternative antiemetic regimens. A mail-in questionnaire
      for monitoring nausea and vomiting in outpatients undergoing chemotherapy was
      completed and returned by a high percentage of patients and was useful to clinic
      pharmacists.

PMID- 9784769
TI  - Cost of managing anemia with and without prophylactic epoetin alfa therapy in
      breast cancer patients receiving combination chemotherapy.
AB  - The cost of managing anemia with prophylactic epoetin alfa therapy versus blood
      transfusions in breast cancer patients receiving combination chemotherapy was
      studied. A retrospective study of anemia in breast cancer patients treated with
      four cycles of cyclophosphamide and doxorubicin with fluorouracil (CAF) or
      without fluorouracil (CA) was conducted. For each cycle of chemotherapy, patients
      were assessed for fatigue, subsequent blood transfusions administered, and
      potential response to and adverse effects of blood transfusions. Transfusions
      were given at the prescriber's discretion rather than in accordance with standard
      guidelines. The lowest hemoglobin concentration and hematocrit of each patient
      per cycle were reported. Data on these patients, along with data from published
      studies of prophylactic use of epoetin alfa, were used in a decision analysis of
      the costs associated with using epoetin alfa versus red blood cell transfusions
      to manage anemia. The charts of 50 patients were reviewed. In the study group,
      the percentage of patients with anemia and the frequency of fatigue rose with
      each chemotherapy cycle. In general, blood transfusions were not used. The cost
      of using epoetin alfa prophylactically for all four cycles was estimated at $6483
      per patient for the literature-based group versus $169 for the study group. The
      cost of managing anemia in breast cancer patients was substantially lower when
      blood transfusions were used than when epoetin alfa was given prophylactically
      throughout four cycles of therapy with CAF or CA; the absence of standard
      guidelines for transfusion might have exaggerated the difference in costs.

PMID- 9784771
TI  - Staff attitudes about the use of robots in pharmacy before implementation of a
      robotic dispensing system.
AB  - Hospital pharmacy staff members at a Mid-western university medical center were
      surveyed to determine their attitudes about the use of robots in pharmacy
      dispensing before a robotic system was implemented. A questionnaire seeking
      attitudes about the use of robots in pharmacy was distributed to 147 pharmacy
      staff (pharmacy managers, pharmacist practitioners, pharmacotherapists, pharmacy
      residents and fellows, pharmacy technicians, and salaried pharmacy students).
      Attitudinal items were scored on a 5-point scale ranging from very favorable to
      very unfavorable. The response rate was 75%. Overall, staff expressed favorable
      attitudes in terms of job security, professional impact, and general robotics
      orientation. Pharmacy managers and pharmacotherapists were the most likely to
      report feeling secure about their jobs; pharmacy technicians and salaried
      pharmacy students were slightly less positive. Favorable attitudes about the
      professional impact of the robotic system were demonstrated by all groups except
      pharmacist practitioners and pharmacy technicians. Attitudes about management
      issues were unfavorable; pharmacist practitioners demonstrated the least
      favorable attitudes. In general, responses to semantic-differential statements
      reflected favorable attitudes; where there were differences, pharmacy technicians
      showed the least positive and pharmacy managers the most positive attitudes.
      Respondents reported that pharmacist practitioners would be most positively
      affected and pharmacy technicians most negatively affected by robotic dispensing.
      Almost half of the respondents who provided general comments indicated that they
      needed more information about the use of robots. Pharmacy staff had generally
      favorable attitudes about the use of robots in pharmacy.

PMID- 9784772
TI  - Stability of alprazolam, chloroquine phosphate, cisapride, enalapril maleate, and
      hydralazine hydrochloride in extemporaneously compounded oral liquids.
AB  - The stability of five drugs commonly prescribed for use in oral liquid dosage
      forms but not commercially available as such was studied. Alprazolam 1 mg/mL,
      chloroquine phosphate 15 mg/mL, cisapride 1 mg/mL, enalapril maleate 1 mg/mL, and
      hydralazine hydrochloride 4 mg/mL were each prepared in a 1:1 mixture of Ora
      Sweet and Ora-Plus (Paddock Laboratories), a 1:1 mixture of Ora-Sweet SF and Ora
      Plus, and cherry syrup and placed in 120-mL amber clear polyethylene
      terephthalate bottles. Three bottles of each liquid were stored at 5 degrees C
      and three at 25 degrees C, all in the dark. Samples were taken initially and at
      various times up to 60 days for analysis by high-performance liquid
      chromatography and assessment of appearance and odor; pH was measured. A mean of
      at least 91% of the initial drug concentration was retained for 60 days in the
      alprazolam, chloroquine phosphate, cisapride, and enalapril maleate liquids. The
      hydralazine hydrochloride liquids retained more than 90% of the initial
      concentration for only one day at 5 degrees C when prepared with Ora-Sweet-Ora
      Plus and two days when prepared with Ora-Sweet SF-Ora-Plus and for less than a
      day in these preparations at 25 degrees C and in cherry syrup at 5 and 25 degrees
      C. No substantial changes in the appearance, odor, or pH of any liquid were
      observed. Alprazolam 1 mg/mL, chloroquine phosphate 15 mg/mL, cisapride 1 mg/mL,
      and enalapril maleate 1 mg/mL were stable in three extemporaneously compounded
      oral liquids for 60 days at 5 and 25 degrees C; hydralazine hydrochloride 4 mg/mL
      was stable at 5 degrees C for one day in Ora-Sweet-Ora Plus and for two days in
      Ora-Sweet SF-Ora-Plus.

PMID- 9784773
TI  - Protocol for initial evaluation of occupational exposure to HIV and initiation of
      antiretroviral prophylaxis.

PMID- 9784774
TI  - Discrepancies with automated drug storage and distribution cabinets.

PMID- 9784775
TI  - Standards of practice: the African experience.

PMID- 9784776
TI  - Mibefradil and an effective formulary system.

PMID- 9784777
TI  - Differences in warfarin products are not the issue.

PMID- 9784778
TI  - Citalopram approved for treatment of depression.

PMID- 9784780
TI  - Studies highlight low use of beta-blockers.

PMID- 9784779
TI  - Study of estrogen-progestin for secondary prevention yields unexpected results.

PMID- 9784781
TI  - Medicare HMO promotions paint rosy picture, lack details.

PMID- 9784782
TI  - Protecting children in the community from poisons.

PMID- 9784783
TI  - National Pharmacy Week--all year long.

PMID- 9784784
TI  - Anagrelide, a selective thrombocytopenic agent.
AB  - The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and
      dosage and administration of anagrelide are reviewed. Anagrelide is a selective
      thrombocytopenic agent with FDA-approved labeling for the treatment of essential
      thrombocythemia. Clinical trials have shown that the drug may have a role in the
      treatment of other chronic myeloproliferative disorders, including polycythemia
      vera, chronic myeloid leukemia, and agnogenic myeloid metaplasia. The mechanism
      by which anagrelide reduces platelet count is not yet clear. The current
      hypothesis is that anagrelide affects the late (postmitotic) phases of
      megakaryocyte development. Anagrelide has a large volume of distribution and is
      extensively metabolized; less than 1% is recovered unchanged in the urine. Plasma
      half-life after a 0.5-mg dose is 1.3 hours. Anagrelide's efficacy and safety have
      been evaluated in open-label, noncomparative trials, in which the response rate
      was 60-93%. Adverse effects include headache, diarrhea, edema, palpitations, and
      abdominal pain. Patients with renal or hepatic dysfunction need to be closely
      monitored for signs of toxicity. The recommended starting dosage is 0.5 mg four
      times a day or 1 mg twice a day, with dosage adjustment to the lowest effective
      amount required to reduce and maintain platelet count below 600 x 10(9)/L. The
      wholesale acquisition price for 0.5-mg capsules is $350 per 100. Whether
      anagrelide will replace hydroxyurea as first-line therapy in some or all patients
      remains to be determined. Anagrelide is effective in the treatment of essential
      thrombocythemia and may have a role in the treatment of other myeloproliferative
      disorders.

PMID- 9784785
TI  - Strategies in the treatment of penicillin-resistant Streptococcus pneumoniae.
AB  - The epidemiology, resistance mechanisms, susceptibility testing, treatment,
      prevention, and clinical importance of penicillin-resistant Streptococcus
      pneumoniae (PRSP) infection are discussed. PRSP is an established presence in the
      United States, with some geographic areas reporting decreased susceptibility in
      up to half of isolates. The mechanism of resistance to beta-lactam antibiotics in
      S. pneumoniae is genetic changes resulting in decreased binding of drug to the
      bacterial cell wall. Emerging PRSP strains have necessitated testing as a tool in
      selecting drugs for treating life-threatening infections. Opinions differ on how
      to treat these infections empirically. Non-life-threatening infections, such as
      otitis media, are still often treated successfully with amoxicillin, amoxicillin
      clavulanate potassium, or a third-generation cephalosporin. Currently recommended
      initial treatment of pneumococcal pneumonia in otherwise healthy patients
      requiring hospitalization consists of cefuroxime, ceftriaxone, or cefotaxime;
      some authors continue to emphasize injectable penicillin. Once the mainstay of
      empirical treatment of pneumococcal meningitis, penicillin has largely been
      abandoned in favor of cefotaxime or ceftriaxone. Vaccination remains an
      underutilized strategy in atrisk populations. The clinical importance of
      penicillin resistance among pneumococci is still uncertain. Changing patterns in
      the susceptibility of S. pneumoniae to penicillin make selection of appropriate
      therapy increasingly difficult. Key considerations are the site of infection and
      the level of resistance.

PMID- 9784786
TI  - Meta-analysis of streptokinase and heparin in deep vein thrombosis.
AB  - The efficacy and safety of streptokinase and heparin in deep vein thrombosis
      (DVT) were compared in a meta-analysis. Randomized trials in which streptokinase
      (followed by heparin) and heparin alone were compared in treating
      phlebographically documented acute DVT were identified from MEDLINE and other
      sources for a meta-analysis. Odds ratios (ORs) and 95% confidence intervals (CIs)
      based on the logit method were computed for each study. A fixed-effect model was
      used to combine the study results, enabling differences between streptokinase
      recipients and recipients of heparin alone to be expressed as summary ORs with
      95% CIs. Significantly more streptokinase recipients achieved thrombolysis than
      recipients of heparin alone (summary OR, 6.24; 95% CI, 3.62 to 10.78). One study
      was identified as an outlier and excluded from the analysis. The meta-analysis
      then showed that streptokinase recipients were significantly less likely to have
      postthrombotic changes (summary OR, 0.40; 95% CI, 0.18 to 0.88) and postphlebitic
      changes (summary OR, 0.32; 95% CI, 0.12 to 0.86) in phlebographic evaluation. The
      frequency of major bleeding was significantly higher among streptokinase
      recipients than recipients of heparin alone (summary OR, 3.78; 95% CI, 1.26 to
      11.32). A meta-analysis showed that, compared with heparin alone, streptokinase
      therapy for DVT was associated with significantly more frequent thrombolysis and
      major bleeding; after exclusion of one outlying study, analysis showed that
      streptokinase therapy was associated less frequently than heparin alone with
      postthrombotic changes (assessed by phlebographic evaluation) and postphlebitic
      syndrome.

PMID- 9784787
TI  - Establishing an institution-specific therapeutic range for heparin.
AB  - The relationship between heparin concentration and activated partial
      thromboplastin time (aPTT) in pooled plasma was compared with that in patient
      samples to assess the feasibility of using heparin-spiked pooled plasma in
      determining a therapeutic range for aPTT. Blood samples were taken from 32
      patients who had been receiving intravenous unfractionated heparin sodium for
      more than 24 hours. The samples were stored at -70 degrees C until anti-Xa assay
      within three months of collection. Pooled normal plasma was spiked with
      unfractionated heparin sodium to produce nominal anti-Xa concentrations of 0,
      0.05, 0.1, 0.2, and 0.5 unit/mL. Heparin concentrations and a aPTT values were
      measured, and the relationship between the two was determined by linear
      regression. For the ex vivo samples, the range of aPTT values corresponding to
      therapeutic heparin concentrations of 0.3-0.7 anti-Xa unit/mL was 64-106 seconds,
      which corresponds to an aPTT range of 2.3-3.9 times the mean of the normal range
      (compared with the traditionally defined therapeutic range of 1.5-2.5 times the
      control value). For the in vitro samples, the aPTT range corresponding to heparin
      concentrations of 0.3-0.7 unit/mL was 121-256 seconds, which corresponds to an
      aPTT range of 4.4-9.4 times the mean of the normal range. Each institution should
      establish a therapeutic aPTT range by calibrating aPTT values against heparin
      concentrations from blood samples of patients receiving intravenous heparin.

PMID- 9784788
TI  - Drug information resources in managed care organizations.

PMID- 9784789
TI  - Provision of pharmaceutical care by community pharmacists in Northern Ireland.

PMID- 9784791
TI  - Acute paranoid reaction to saquinavir.

PMID- 9784790
TI  - Stability of lorazepam 1 and 2 mg/mL in glass bottles and polypropylene syringes.

PMID- 9784792
TI  - The U.S. home infusion market.
AB  - Medicare legislation stimulated the development of home care services but also
      resulted in fragmentation of service components. In the 1980s, prospective
      pricing and diagnosis-related groups, and resulting pressures to reduce inpatient
      length of stay, prompted additional growth of the industry. Even so, in 1995 home
      care represented only 3% of total national expenditures on health care. The
      annual growth rate of the home infusion industry dropped from 64% in 1982-86 to
      24% in 1986-93. While revenue per patient for home infusion is expected to
      decrease under managed care, an increasing number of patients will support
      continued market growth. The home infusion market is highly competitive, with
      only a few large national providers and many small local providers. In 1996, 29%
      of acute care hospitals provided or were developing a home care program.
      Community pharmacists' options in the home infusion area include independent
      services, partnerships, joint ventures, contracts with hospitals, and franchises.
      The home infusion market is being integrated into alternative sites, such as
      ambulatory infusion centers (AICs), as providers attempt to diversify to maintain
      managed care contracts. AICs provide infusion therapy and nursing to
      noninstitutionalized, nonhome-bound patients. Untapped sources for future growth
      of the infusion market include long-term-care facilities. More consistent studies
      of the home care market are needed. Despite slowed growth in recent years, home
      care has a strong market in the United States.

PMID- 9784793
TI  - Abciximab vials as multidose containers.

PMID- 9784794
TI  - Pearls in therapeutic drug monitoring.

PMID- 9784795
TI  - Shifting paradigms of antiplatelet therapy: assessing new drugs versus old.
      Introduction.

PMID- 9784796
TI  - Atherosclerosis: a unifying disorder with diverse manifestations.
AB  - The epidemiology, costs, and comorbidities associated with atherosclerosis and
      the role of newer antiplatelet agents are reviewed. Cardiovascular disease is the
      leading cause of death in the United States. More than 60 million Americans have
      one or more types of cardiovascular disease. The total annual cost of coronary
      heart disease has been estimated at $95 billion. Patients with an existing
      atherosclerotic disease in one vascular bed are at high risk of having an
      ischemic vascular event in the same or another vascular bed. Peripheral arterial
      disease is a strong marker for underlying cerebrovascular and cardiovascular
      disease. The common link among these diseases is atherosclerosis leading to
      atherothrombosis. Platelets play an integral role in atherosclerosis and the
      formation of arterial thrombus as well as in subsequent acute events such as
      ischemic stroke, myocardial infarction, and vascular death. Arterial thrombosis
      can be mediated by shear-stress-induced platelet aggregation. Currently, only one
      third to one half of all eligible patients with stroke, myocardial infarction, or
      peripheral arterial disease receive antiplatelet therapy. Thienopyridines such as
      ticlopidine and clopidogrel are effective inhibitors of shear-stress-induced and
      endothelial-injury-induced platelet aggregation. Advances in antiplatelet therapy
      provide an opportunity to use newer antiplatelet agents in the prevention of
      atherosclerosis-related morbidity and mortality; therapeutic approaches should be
      directed toward recognizing atherosclerosis as a generalized disease process and
      preventing ischemic events in multiple vascular beds.

PMID- 9784797
TI  - Antiplatelet therapy in coronary artery disease: review and update of efficacy
      studies.
AB  - The mechanisms of action of currently available and newer antiplatelet agents and
      evidence of the efficacy of antiplatelet agents for primary and secondary
      prevention of coronary artery disease are reviewed. Available data do not support
      the widespread use of aspirin for primary prevention of cardiovascular disease.
      Patients over the age of 50 years with at least one additional risk factor for
      coronary artery disease may benefit, although possibly at an increased risk of
      hemorrhagic stroke. Aspirin is recommended for secondary prevention of vascular
      disease in patients with stable or unstable angina, clinical or laboratory
      evidence of coronary artery disease, history of myocardial infarction, or history
      of stroke or transient ischemic attack. There are no data supporting a role for
      dipyridamole for primary or secondary prevention of ischemic heart disease.
      Abciximab has been shown to reduce the risk of cardiovascular complications at 30
      days after percutaneous transluminal coronary angioplasty in patients with
      refractory unstable angina. Studies with other glycoprotein IIb/IIIa-receptor
      antagonists, including eptifibatide, tirofiban, and lamifiban, have yielded
      promising results. Ticlopidine may be used for secondary prevention of
      cardiovascular disease in patients with unstable angina who are allergic to or
      intolerant of aspirin. Clopidogrel has been shown to be safe and effective for
      secondary prevention of vascular events. Aspirin has a role in secondary
      prevention of coronary artery disease; among patients who are allergic to or
      intolerant of aspirin, ticlopidine has a role in patients with unstable angina
      and clopidogrel has a potential role in patients with ischemic heart or vascular
      disease.

PMID- 9784798
TI  - Clinical considerations in selecting antiplatelet therapy in cerebrovascular
      disease.
AB  - Effective antiplatelet drugs--aspirin, ticlopidine, dipyridamole, and clopidogrel
      -are reviewed. Aspirin has remained the pharmacologic foundation of stroke
      prevention, primarily because of its low cost. It has been shown to provide a 22%
      relative risk reduction of stroke in high-risk patients. Its principal adverse
      effect is gastrotoxicity. Ticlopidine has been widely used in patients with a
      high risk of stroke who are sensitive to aspirin or in whom aspirin has failed.
      It has been associated with a median reduction in adenosine diphosphate-induced
      platelet aggregation of 70% in about 8-11 days. Ticlopidine has been shown to be
      superior to aspirin at three years in preventing stroke. The principal adverse
      effects are diarrhea and rash; there has been a 2.4% occurrence of neutropenia.
      In a trial comparing aspirin, dipyridamole, and a combination of the two, the
      risk of stroke was 18% lower with aspirin, 16% lower with dipyridamole, and 37%
      lower with combination therapy compared with placebo. The adverse-effect profile
      of dipyridamole has proven to be less problematic than that of aspirin or
      ticlopidine. In a trial comparing clopidogrel with aspirin, patients receiving
      clopidogrel had an annual 5.32% risk of ischemic stroke, myocardial infarction,
      or vascular death compared with 5.83% for patients receiving aspirin. Clopidogrel
      has been associated with a small occurrence of rash and diarrhea, and
      gastrointestinal intolerance and hemorrhage were less frequent with clopidogrel
      than with aspirin. Both aspirin and clopidogrel are associated with a low
      occurrence of neutropenia. Aspirin, ticlopidine, dipyridamole, and clopidogrel
      have earned a role in stroke prevention; the different adverse-effect profiles of
      the drugs will influence the choice of agent.

PMID- 9784799
TI  - Management of peripheral arterial disease.
AB  - The risk factors, epidemiology, diagnosis, and treatment of peripheral arterial
      disease are reviewed. Peripheral arterial disease is characterized by a gradual
      reduction in blood flow to one or more limbs secondary to atherosclerosis. Risk
      factors include smoking, diabetes mellitus, hyperlipidemia, and hypertension. The
      most common clinical manifestation is intermittent claudication. The prevalence
      of intermittent claudication in people over the age of 50 is 2-7% for men and 1
      2% for women. The ankle:brachial pressure index (ABPI) is a useful measure of
      disease severity; an ABPI of 0.5-0.9 is common in intermittent claudication. The
      goals of therapy are to relieve or reduce ischemic symptoms, alleviate
      disability, improve in functional capacity, prevent progression that may result
      in gangrene and limb loss, and prevent cardiovascular and cerebrovascular events.
      Treatment includes risk-factor modification, drug therapy (primarily with
      antiplatelet agents), and revascularization procedures. Aspirin has been shown to
      be effective in reducing the associated risk of myocardial infarction and stroke.
      Ticlopidine appears to be a reasonable alternative for patients who are
      hypersensitive to aspirin. Clopidogrel has been shown to be more effective than
      aspirin in patients with recent myocardial infarction, recent stroke, or
      established peripheral arterial disease. There is controversy over the
      appropriate treatment for acute arterial occlusions. Risk-factor modification and
      antiplatelet drugs are the mainstays of therapy for patients with intermittent
      claudication, the most common manifestation of peripheral arterial disease.

PMID- 9784801
TI  - Expression and localization of the Th2-type cytokine interleukin-13 and its
      receptor in the placenta during human pregnancy.
AB  - PROBLEM: To investigate the expression of the Th2-type cytokine interleukin (IL)
      13 and its receptor in human placenta during gestation. METHOD OF STUDY:
      Expression of IL-13 and its receptor was analyzed by reverse transcriptase (RT)
      polymerase chain reaction (PCR), in situ hybridization and immunohistochemistry
      using human placental samples. RESULTS: IL-13 mRNA was detected by RT-PCR in
      placental extracts from all stages of gestation. In situ hybridization revealed
      IL-13 mRNA in first trimester cytotrophoblast and syncytiotrophoblast. Few
      positive cells were found within decidual sections from the same pregnancy.
      Immunohistochemistry revealed a similar pattern to in situ hybridization. This
      was largely absent in second- and third-trimester placentae. IL-13 receptor alpha
      chain (IL-13R alpha) was detected by immunofluorescence on the surface of
      leukocytes in first-trimester villous core and decidua. CONCLUSIONS: The
      expression of IL-13 is spatially and temporally regulated in the placenta, and
      associated with the close proximity of a receptor-bearing target leukocyte
      population.

PMID- 9784800
TI  - Formulary and economic considerations in the selection of antiplatelet agents.
AB  - A pharmacoeconomic model for evaluating antiplatelet therapies is described. In
      order to conduct a pharmacoeconomic analysis, it is important to understand the
      course of the disease under study and the prevention and treatment options,
      identify the associated economic consequences, develop concomitant strategies,
      and target high-yield decisions. The steps of a pharmacoeconomics-based decision
      are defining the pharmacoeconomic problem, creating a cross-functional team,
      determining the study's perspective, determining the treatment alternatives and
      outcomes, selecting the appropriate pharmacoeconomic method, placing a monetary
      value on outcomes, identifying resources and data sources, establishing
      probabilities of outcomes, using decision analysis, undertaking a cost or
      sensitivity analysis, presenting the results, developing and implementing a
      policy or clinical intervention based on the results, educating health care
      professionals about the new policy or intervention, and documenting the quality
      of care and potential cost savings through follow-up. Clopidogrel is given as an
      example. The composite endpoint of myocardial infarction, stroke, or vascular
      death has been shown to be 8.7% lower with clopidogrel than with aspirin in
      patients with recent myocardial infarction, recent ischemic stroke, or
      symptomatic peripheral arterial disease. Clopidogrel costs more than aspirin but
      may be considered as first-line therapy for high-risk patients, patients who are
      allergic to aspirin, or patients who cannot tolerate the gastrointestinal effects
      of aspirin. Cost-effectiveness analyses can be used to support formulary
      decisions about which antiplatelet agent should be used; the use of a particular
      agent ultimately also depends on efficacy, safety, pharmacodynamics, patient
      specific factors, and relative direct and indirect costs.

PMID- 9784802
TI  - Increased mast cell density in peritoneal endometriosis compared with eutopic
      endometrium with endometriosis.
AB  - PROBLEM: Factors regulating fibrosis in peritoneal endometriosis are poorly
      understood. We hypothesized that mast cell proteases may play a role in the
      process of fibrosis in peritoneal endometriosis. As the first step in examining
      the possible contribution of mast cells to fibrosis, we investigated their
      distribution in peritoneal endometriosis lesions according to their macroscopic
      appearance. METHOD OF STUDY: Mast cells were identified by immunohistochemistry
      using monoclonal antibody against mast cell tryptase on formalin-fixed, paraffin
      embedded sections. Mast cell density (mean mast cell count per 0.13 mm2 of
      stroma) was measured using a computerized image analysis system. RESULTS: Mast
      cell density was significantly increased in black peritoneal lesions compared
      with red peritoneal lesions in endometriosis. CONCLUSIONS: Mast cells may be
      involved in the pathogenesis of peritoneal endometriosis.

PMID- 9784803
TI  - Effects of pregnancy on lymphocytes within sheep uterine interplacentomal
      epithelium.
AB  - PROBLEM: Previous studies demonstrate increases in the number and granularity of
      gamma delta T cells within the sheep uterine interplacentomal epithelium during
      pregnancy. To further characterize their activation and function, gamma delta T
      cell receptor (TCR)+ intraepithelial lymphocytes (IELs) from nonpregnant and
      pregnant uteri were phenotyped extensively. Cytokine mRNA expression in the
      epithelium and by gamma delta TCR+ IELs isolated from pregnant uteri was also
      examined. METHOD OF STUDY: Cell suspensions were prepared from the uterine
      interplacentomal epithelium and from the peripheral blood of nonpregnant and
      pregnant ewes (120-140 days of gestation). Surface marker expression was
      determined by two-color flow cytometry and cytokine expression determined by
      reverse transcriptase--polymerase chain reaction. RESULTS: Uterine gamma delta
      TCR+ IELs exhibited increased beta 1-integrin expression but decreased leukocyte
      function associated antigen (LFA)-1 and major histocompatibility complex class I
      expression during pregnancy. Major histocompatibility complex class II, CD44,
      CD2, and LFA-3 expression was unchanged during pregnancy, whereas CD25, VLA-4 and
      L-selectin were never expressed. The same cytokines were expressed in the
      pregnant and nonpregnant uterine interplacentomal epithelium with detectable mRNA
      for interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and interleukin
      (IL)-1 alpha, but not for IL-2 or IL-4. gamma delta TCR+ and CD8+ IEL purified
      from pregnant uteri expressed mRNA for IFN-gamma, TNF-alpha, transforming growth
      factor-beta, and IL-10. CONCLUSIONS: gamma delta TCR+ IELs from pregnant uteri
      have cytoplasmic granules, and express CD8 and cytokines indicative of cytotoxic
      potential. Phenotypic changes induced during pregnancy differed from those
      observed after activation of circulating naive cells and may represent further
      stimulation of fully differentiated effectors. gamma delta TCR+ IELs are present
      only in interplacentomal areas of pregnant uteri and may control trophoblast
      invasion within these areas.

PMID- 9784804
TI  - The active compression test: a new and effective test for diagnosing labral tears
      and acromioclavicular joint abnormality.
AB  - Labral tears and acromioclavicular joint abnormalities were differentiated on
      physical examination using a new diagnostic test. The standing patient forward
      flexed the arm to 90 degrees with the elbow in full extension and then adducted
      the arm 10 degrees to 15 degrees medial to the sagittal plane of the body and
      internally rotated it so that the thumb pointed downward. The examiner, standing
      behind the patient, applied a uniform downward force to the arm. With the arm in
      the same position, the palm was then fully supinated and the maneuver was
      repeated. The test was considered positive if pain was elicited during the first
      maneuver, and was reduced or eliminated with the second. Pain localized to the
      acromioclavicular joint or "on top" was diagnostic of acromioclavicular joint
      abnormality, whereas pain or painful clicking described as "inside" the shoulder
      was considered indicative of labral abnormality. A prospective study was
      performed on 318 patients to determine the sensitivity, specificity, and positive
      and negative predictive values of the test. Fifty-three of 56 patients whose
      preoperative examinations indicated a labral tear had confirmed labral tears that
      were repaired at surgery. Fifty-five of 62 patients who had pain in the
      acromioclavicular joint and whose preoperative examinations indicated
      abnormalities in the joint had positive clinical, operative, or radiographic
      evidence of acromioclavicular injury. There were no false-negative results in
      either group.

PMID- 9784805
TI  - Association between the menstrual cycle and anterior cruciate ligament injuries
      in female athletes.
AB  - Anterior cruciate ligament injury rates are four to eight times higher in women
      than in men. Because of estrogen's direct effect on collagen metabolism and
      behavior and because neuromuscular performance varies during the menstrual cycle,
      it is logical to question the menstrual cycle's effect on knee injury rates. Of
      40 consecutive female athletes with acute anterior cruciate ligament injuries
      (less than 3 months), 28 (average age, 23 +/- 11 years) met the study criteria of
      regular menstrual periods and noncontact injury. Details concerning mechanism of
      injury, menstrual cycle, contraceptive use, and previous injury history were
      collected. A chi-square test was used to compute observed and expected
      frequencies of anterior cruciate ligament injury based on three different phases
      of the menstrual cycle: follicular (days 1 to 9), ovulatory (days 10 to 14), and
      luteal (day 15 to end of cycle). A significant statistical association was found
      between the stage of the menstrual cycle and the likelihood for an anterior
      cruciate ligament injury (P = 0.03). In particular, there were more injuries than
      expected in the ovulatory phase of the cycle. In contrast, significantly fewer
      injuries occurred in the follicular phase. These hormones may be a factor in the
      knee ligament injury dilemma in women.

PMID- 9784806
TI  - Biomechanics of a less invasive procedure for reconstruction of the ulnar
      collateral ligament of the elbow.
AB  - A reconstruction of the anterior bundle of the ulnar collateral ligament of the
      elbow using bone anchors was compared regarding strain and valgus load strength
      with the intact ulnar collateral ligament and the reconstructed ulnar collateral
      ligament using bone tunnels. In both normal and reconstructed elbows, the
      anterior band and posterior band were tight during only a portion of the range of
      motion. Toward extension, the mean peak strain in the anterior band was tight for
      the normal and bone anchor groups, but lax in the bone tunnel group. Toward
      extension, the mean peak strain in the posterior band was lax in all elbows.
      Toward flexion, the strain in the anterior band was lax in the normal and bone
      anchor groups, but tight in the bone tunnel group. The mean of the peak strains
      for the posterior band toward flexion was tight for all elbows. Mean valgus load
      strength of normal elbows was 22.7 +/- 9.0 N.m. The bone tunnel and bone anchor
      mean strengths were 76.3% and 63.5%, respectively, of normal elbow strength. We
      concluded that the bone anchor reproduced the normal anatomy and mechanical
      function of the ulnar collateral ligament more closely than the bone tunnel, and
      that both reconstruction methods were significantly weaker than the normal ulnar
      collateral ligament. However, we found no significant difference in
      reconstruction strength between bone anchor and bone tunnel.

PMID- 9784808
TI  - Meniscal repair in the young athlete.
AB  - Twenty-nine meniscal repairs in 26 patients 17 years of age or younger were
      performed using arthroscopic techniques. Clinical follow-up examinations were
      performed and the SF-36 Health Status Survey and International Knee Documentation
      Committee evaluation form were administered. A Lysholm score was determined for
      each patient. All 26 patients were seen for follow-up at an average of 5.0 years
      (range, 2.0 to 13.5). All patients had a full range of motion with no effusion,
      joint line tenderness, or McMurray sign present at the time of examination. No
      patient experienced symptoms of locking. No patient underwent repeat surgery for
      a nonhealed meniscal repair. The clinical healing rate in this group was 100%.
      The SF-36 data demonstrated an average physical functioning score of 91 and an
      average role physical score of 91. The average Lysholm score was 90. Twenty-two
      patients (85%) were performing level I activities based on the International Knee
      Documentation Committee rating. Excellent rates of healing, even higher than
      those obtained in the adult population, can be obtained with meniscal repairs
      performed in this young age group.

PMID- 9784807
TI  - Open capsulorrhaphy with suture anchors for recurrent anterior dislocation of the
      shoulder.
AB  - Forty of 42 consecutive open capsulorrhaphies with suture anchors for treatment
      of traumatic recurrent anterior dislocation of the shoulder were reviewed after a
      minimum follow-up of 2 years. Two patients were lost to follow-up. Follow-up was
      conducted according to the rating systems of Rowe and the Society of American
      Shoulder and Elbow Surgeons. The surgical outcome was satisfactory in 38 patients
      (95%). Eighteen of the 22 patients who were involved in competitive overhead or
      collision sports before surgery returned to their preoperative sports levels. One
      patient, whose operation was unsuccessful, experienced recurrent dislocation. In
      one patient a deep infection that occurred as a complication of the surgical
      technique healed after suture anchor removal. Although a longer follow-up is
      necessary, this technique appears to have encouraging results as it avoids the
      risks related to the use of screws and staples.

PMID- 9784809
TI  - Analysis of collagen and elastic fibers in shoulder capsule in patients with
      shoulder instability.
AB  - This study examined collagen cross-links, collagen fibril diameter and density,
      amino acid composition, and elastic fibers in shoulder capsule and skin in four
      patient groups: 1) unidirectional anterior instability (N = 8); 2)
      multidirectional instability/primary surgery (N = 6); 3) multidirectional
      instability/revision surgery (N = 6); and 4) no history of instability (N = 5).
      Compared with normal capsule, capsule from groups 1 and 2 had more stable and
      reducible collagen cross-links, significantly greater mean collagen fibril
      diameter, more cysteine, and a higher density of elastin staining. Compared with
      shoulder capsule in groups 1 and 2, shoulder capsule from group 3 contained
      significantly more reducible cross-links, smaller-diameter collagen fibrils,
      decreased collagen fibril density, and an increased density of elastin staining.
      There were no significant differences in any parameters between groups 1 and 2.
      We hypothesized that repeated capsular deformation in patients with shoulder
      instability results in changes in the capsule that increase its strength and
      resistance to stretching. Skin analyses demonstrated a significantly smaller mean
      collagen fibril diameter in skin from group 2 compared with group 1, suggesting
      the possibility of an underlying connective tissue abnormality.

PMID- 9784810
TI  - Acute skier's thumb repaired with a proximal phalanx suture anchor.
AB  - The purpose of this study was to determine the functional outcome of a surgical
      technique for the repair of injuries of the ulnar collateral ligament of the
      thumb. A 14-point questionnaire was developed to determine functional outcome
      after surgical repair of acute ulnar collateral ligament rupture. Early ulnar
      collateral ligament repair was performed on 58 patients with grade III sprains
      (complete rupture) of the ligament using a new technique that employs a suture
      anchor for fixation. Forty-five patients were interviewed at a minimum
      postoperative interval of 12 months and were included in this study. Forty-four
      patients (98%) believed they had a stable repair, were satisfied with their
      surgery, and would have it again if necessary. Forty-four patients (98%) were not
      hindered in their day-to-day activities and had a functional range of motion.
      Mild discomfort was felt by eight of our patients (17%), but only three patients
      (7%) had pain with activities. The average time to return to skiing was 1.7 days.
      The use of a suture anchor provided a strong and stable repair if the surgery was
      performed early.

PMID- 9784811
TI  - Disruption of the finger flexor pulley system in elite rock climbers.
AB  - We treated 13 elite rock climbers for isolated disruptions of the pulleys of the
      long fingers. Diagnosis and treatment were based on the clinical finding of bow
      stringing, which was confirmed by magnetic resonance imaging. Eight patients had
      bowstringing indicating incomplete disruption of the major pulley A2 and were
      treated nonoperatively (group A). Five patients showed bowstringing indicating
      complete disruption of the pulley A2. After failed nonoperative treatment, the
      pulleys were reconstructed (group B). The mechanism of injury and clinical and
      subjective results were evaluated. At a 31-month follow-up (range, 18 to 43
      months), loss of extension in the proximal interphalangeal joint measured 5.6
      degrees (range, 0 degree to 10 degrees) in group A and 4 degrees (range, 0 degree
      to 10 degrees) in group B. Circumference of the finger section was increased 4.2
      mm in group A (range, 0 to 10 mm) and 4.8 mm in group B (range, 0 to 10 mm). Grip
      strength decreased 20 N in group A (range, 10 to 50 N) and 12 N in group B
      (range, 10 to 30 N). Four patients in group A and one in group B had bowstringing
      at clinical evaluation. On follow-up magnetic resonance images, bowstringing
      remained unchanged in group A but was reduced in all patients in group B. Good
      subjective results were seen in both groups.

PMID- 9784813
TI  - Isometry of the posterior cruciate ligament. Effects of functional load and
      muscle force application.
AB  - The effects of functional load and muscle force application on isometry of the
      posterior cruciate ligament were determined. Eight fresh-frozen cadaver knees
      were mounted in a custom-designed rig. A full range of motion and muscle forces
      were applied through the quadriceps, hamstring, and gastrocnemius tendons during
      a simulated static squat maneuver. The low-load isometric posterior cruciate
      ligament point was located 5.63 mm proximal and 0.18 mm anterior to the anatomic
      center of the posterior cruciate ligament origin on the femur. The high-load
      state, with no gastrocnemius and hamstring muscle forces applied, shifted the
      isometric point 6.32 mm proximal and 6.72 mm anterior (P < 0.05). Loading the
      hamstring and gastrocnemius muscles also shifted the isometric point (P < 0.05).
      This study indicated that the most isometric region of the posterior cruciate
      ligament femoral attachment changed significantly when functional loads and
      muscle forces were applied to the knee. This finding may have implications for
      both surgical reconstruction and rehabilitation of the posterior cruciate
      ligament-injured knee.

PMID- 9784812
TI  - Reconstruction of the lateral collateral ligament of the knee with patellar
      tendon allograft. Report of a new technique in combined ligament injuries.
AB  - This is a retrospective study of 10 patients with combined cruciate ligament and
      posterolateral instability who underwent surgical reconstruction between 1991 and
      1994. All knees had at least 20 degrees increased external rotation at 30 degrees
      of knee flexion and from 1+ to 3+ varus instability. Five knees with posterior
      cruciate ligament ruptures had at least a 2+ Lachman test result. (One knee had
      both anterior and posterior cruciate ligament injuries). In all cases the lateral
      collateral ligament was reconstructed with a bone-patellar tendon-bone allograft
      secured with interference screws. Fixation tunnels were placed in the fibular
      head and at the isometric point on the femur. The cruciate ligaments were
      reconstructed with autograft or allograft material. The average follow-up was 28
      months. Excessive external rotation at 30 degrees of flexion was corrected in all
      but one knee. Six patients had no varus laxity, and four patients had 1+ varus
      laxity at 30 degrees of flexion. The posterior drawer test result decreased, on
      average, to 1+, and the Lachman test result decreased to between 0 and 1+. The
      average Tegner score was 4.6, with five patients returning to their preinjury
      level of activity and four returning to one level lower. These results indicate
      that this is a promising new procedure for patients with instability resulting
      from lateral ligament injuries of the knee.

PMID- 9784814
TI  - The effects of a popliteus muscle load on in situ forces in the posterior
      cruciate ligament and on knee kinematics. A human cadaveric study.
AB  - To investigate the effect of simulated contraction of the popliteus muscle on the
      in situ forces in the posterior cruciate ligament and on changes in knee
      kinematics, we studied 10 human cadaveric knees (donor age, 58 to 89 years) using
      a robotic manipulator/universal force moment sensor system. Under a 110-N
      posterior tibial load (simulated posterior drawer test), the kinematics of the
      intact knee and the in situ forces in the ligament were determined. The test was
      repeated with the addition of a 44-N load to the popliteus muscle. The posterior
      cruciate ligament was then sectioned and the knee was subjected to the same
      tests. The additional popliteus muscle load significantly reduced the in situ
      forces in the ligament by 9% to 36% at 90 degrees and 30 degrees of flexion,
      respectively. No significant effects on posterior tibial translation of the
      intact knee were found. However, in the ligament-deficient knee, posterior tibial
      translation was reduced by up to 36% of the translation caused by ligament
      transection. A coupled internal tibial rotation of 2 degrees to 4 degrees at 60
      degrees to 90 degrees of knee flexion was observed in both the intact and
      ligament-deficient knees when the popliteus muscle load was added. Our results
      indicate that the popliteus muscle shares the function of the posterior cruciate
      ligament in resisting posterior tibial loads and can contribute to knee stability
      when the ligament is absent.

PMID- 9784815
TI  - Injuries in collegiate wrestling.
AB  - We evaluated the data of the National Collegiate Athletic Association Injury
      Surveillance System on collegiate wrestling with a focus on musculoskeletal
      injuries. Over 800,000 athlete-exposures during an 11-year period compose these
      data. Findings particular to wrestling and a comparison with other collegiate
      sports are included. Collegiate wrestling had a relatively high rate of injury at
      9.6 injuries per 1000 athlete-exposures. It was second to spring football in
      total injury rate. Most injuries in this study were not serious, with 6.3%
      resulting in surgery and 37.6% resulting in a week or more off from wrestling.
      There was only one catastrophic, nonfatal injury. The knee, shoulder, and ankle
      were the most commonly injured regions, and injuries to them were often the more
      serious. Sprains, strains, and contusions were the most common injury types.
      Takedowns and sparring were the most common activities at the time of injury.
      Mechanism of injury was evaluated; rotation about a planted foot and contact with
      environmental objects were identified as areas needing further attention. Illegal
      action accounted for only 4.6% of injuries in competition. Competition had a
      significantly higher injury rate than practice, but the injury profiles of these
      two areas showed both to be equally important. The preseason and regular season
      had higher injury rates than the postseason, but, again, the injury profiles of
      these periods were similar. Injury percentages were similar among the 10 weight
      classes.

PMID- 9784816
TI  - Sports injuries in team handball. A one-year prospective study of sixteen men's
      senior teams of a superior nonprofessional level.
AB  - One hundred eighty-six players of 16 teams in 2 male team handball senior
      divisions were observed prospectively for 1 season to study the injury incidence
      in relation to exposure in games and practices. Ninety-one injuries were
      recorded. Injury incidence was evaluated at 2.5 injuries per 1000 player-hours,
      with a significantly higher incidence in game injuries (14.3 injuries per 1000
      game-hours) compared with practice injuries (0.6 injuries per 1000 practice
      hours). Practice injury incidence was higher in the lower performance level
      group, and game injury incidence was higher in the high-level group. The upper
      extremity was involved in 37% of the injuries, and the lower extremity in 54%.
      The knee was the most commonly injured joint, followed by the finger, ankle, and
      shoulder. Knee injuries were the most severe injuries, and they were more
      frequent in high-level players. There was an increase in the severity of injury
      with respect to performance level. The injury mechanism revealed a high number of
      offensive injuries, one-third of them occurring during a counterattack. The
      injury pattern showed certain variations with respect to player position and
      performance level. Prophylactic equipment was used by a majority of players at
      the higher performance level.

PMID- 9784817
TI  - Intermediate-term results of meniscal repair in anterior cruciate ligament
      reconstructed knees.
AB  - We investigated the incidence of and risk factors for recurrent tears of repaired
      menisci in anterior cruciate ligament-reconstructed knees. We observed 63
      patients whose menisci had been evaluated at second-look arthroscopy as healed (N
      = 50) or incompletely healed (N = 13) for an average of 4 years (range, 2 to
      9.5). Of the 13 patients with incompletely healed menisci, 6 (46%) required
      additional meniscal surgery and 2 (15%) had recurrence of meniscal symptoms such
      as catching or locking. Among the 50 patients with healed menisci, 5 (10%)
      required additional meniscal surgery and 9 (18%) had recurrence of meniscal
      symptoms after second-look arthroscopy. The timing of the recurrence of these
      symptoms was from 12 to 28 months after surgical repair. Of the 11 patients who
      had undergone additional surgery, 6 had sustained second injuries during sports
      activities and the other 5 had no identifiable cause of injury. When comparing
      age, tear sites, rim width, side-to-side differences with KT-1000 arthrometer
      testing, and the pivot shift test, there were no differences between the group
      requiring additional surgery, the symptomatic group, and the asymptomatic group.
      However, the postoperative Tegner activity score of the group requiring
      additional surgery was statistically significantly higher than the others.

PMID- 9784818
TI  - Static and dynamic roentgenographic analysis of ankle stability in braced and
      nonbraced stable and functionally unstable ankles.
AB  - Patients suffering from functional ankle instability were selected based on a
      structured interview. Talar tilt was measured using supine ankle stress
      roentgenographs and standing talar tilt was measured using erect ankle stress
      roentgenographs. A digital roentgenocinematographic analysis of a 50 degrees
      ankle sprain simulation was performed to measure dynamic talar tilt and inversion
      distance between two video images (inversion speed). A significant decrease in
      pathologic supine talar tilt in unstable ankles was found in the braced compared
      with the nonbraced situation (talar tilt = 13.1 degrees versus 4.8 degrees with
      brace). The talar tilt with the brace after activity was still significantly
      lower than the initial value without the brace. The standing talar tilt of
      unstable ankles was shown to be significantly lower with the orthosis than
      without (standing talar tilt = 16.6 degrees versus 12.0 degrees with brace).
      Roentgenocinematographic evaluation of ankle sprain simulation showed that the
      mean dynamic talar tilt during simulated sprain decreased significantly in the
      braced ankles compared with the nonbraced ankles (dynamic talar tilt = 9.8
      degrees versus 6.4 degrees braced). A significant decrease in the digital
      measurement of inversion distance (from 110.6 pixels to 92.4 pixels) was observed
      in the total sample of 39 ankles during the initial high-speed phase of the
      simulated sprain. The brace significantly slows down the inversion speed.

PMID- 9784819
TI  - Quantitative analysis of nerve changes in the lateral retinaculum in patients
      with isolated symptomatic patellofemoral malalignment. A preliminary study.
AB  - Neural damage in 16 lateral retinacula excised at the time of Insall proximal
      realignments or isolated lateral retinacular releases performed in patients with
      symptomatic patellofemoral malalignment was evaluated by means of conventional
      histology and immunohistochemical and morphometric analyses. A relationship
      between clinical and histologic findings was found. An increase in the proportion
      of innervated tissue was correlated with anterior knee pain syndrome. We found a
      significant relationship between total neural area and pain. The group with
      moderate pain had the highest number of nerves and the highest neural area. In
      reference to total neural area and pain, there was a significant difference only
      between the patients with moderate pain and those with light pain, but not
      between patients with severe pain and those with moderate pain. The group with
      severe pain also showed a high neural area, although with a lower number of
      nerves. The severe-pain group had the largest nerves (24% of nerve fibers
      surpassing 25 microns diameter) in a zonal disposition, in which there were
      groups of nerve fibers in some fields and no nerve fibers in others. The group
      with moderate pain had an increase in medium and small nerve fibers (mean
      diameter, 18 microns), predominantly of tiny perivascular fibers. Moreover, we
      believe that instability in patients with patellofemoral malalignment can be
      explained in part because of loss of proprioception due to neural damage.

PMID- 9784820
TI  - Compensatory muscle activity in the posterior cruciate ligament-deficient knee
      during isokinetic knee motion.
AB  - We performed electromyographic analyses in 12 patients with posterior cruciate
      ligament-deficient knees to compare electrical activity in the quadriceps,
      hamstring, and gastrocnemius muscles between the uninjured and involved limbs.
      Each patient performed concentric isokinetic knee motion at 30 and 60 deg/sec in
      both limbs separately. Torques in knee extension and flexion and surface
      electromyograms from the quadriceps, medial hamstring, and medial gastrocnemius
      muscles were simultaneously recorded. The uninjured limb served as a control for
      each patient. Before generation of flexion torque, the gastrocnemius muscle was
      electrically activated significantly earlier in posterior cruciate ligament
      deficient knees than in uninjured knees at each velocity. However, we could not
      find any significant differences between the posterior cruciate ligament
      deficient and uninjured knees in torque curves and electromyelograms of the
      quadriceps and hamstring muscles. This study suggests that early contraction of
      the gastrocnemius muscle may be a part of a compensatory mechanism in posterior
      cruciate ligament-deficient knees.

PMID- 9784822
TI  - Nonunion of the olecranon epiphysis treated with sliding bone graft and tension
      band wire. A case report.

PMID- 9784821
TI  - Effects of patellar tendon adhesion to the anterior tibia on knee mechanics.
AB  - The effects of patellar tendon adhesion on the knee extensor mechanism and on the
      kinematics and contact areas for both the patellofemoral and tibiofemoral joints
      were determined for five cadaveric knees in an open kinetic chain testing
      configuration. Patellar tendon adhesion decreased the distance from the inferior
      patellar pole to the tibial tuberosity, effectively creating patella infera. When
      compared with the controls, knees with adhesion had medial and distal translation
      of the patella, as well as increased patellar flexion. Although the patellar
      articular contact location shifted distally, the overall contact area did not
      change significantly. For the tibia, adhesion resulted in significant medial,
      proximal, and anterior translation, and internal rotation. Adhesion also resulted
      in a posterior shift of the tibial contact location. For the extensor mechanism,
      adhesion decreased the knee extension force created by the quadriceps muscle on
      the tibia, indicating a decrease in the effective moment arm of the extensor
      mechanism. Furthermore, as a result of patellar tendon adhesion, the angle formed
      by the quadriceps and patellar tendons decreased, suggesting an increase in
      patellofemoral joint reaction force with adhesion. The increased patellofemoral
      joint reaction force and the altered contact location may be related to anterior
      knee pain after knee trauma and knee surgery. Therefore, patients should be
      observed for subtle patella infera, which may indicate patellar tendon adhesion.

PMID- 9784823
TI  - Isolated fracture-subluxation of the second sternocostal synchondrosis. A case
      report.

PMID- 9784825
TI  - Correlation of arthroscopic and clinical examinations with magnetic resonance
      imaging findings of injured knees in children and adolescents.

PMID- 9784824
TI  - Upper extremity weight-training modifications for the injured athlete. A clinical
      perspective.
AB  - The ability of the health care professional to make correct decisions about the
      progression of weight-training is critical to the rehabilitation process. The
      purpose of this article is to describe our approach to modification of weight
      lifting techniques using the injured shoulder as a model. Additionally, the
      impact of various upper extremity weight-training techniques on healthy athletes
      is discussed. The effects of grip, hand spacing, bar trajectory, and start and
      finishing positions on microtraumatic injury and return to weight-training
      activities after injury are considered. Several weight-training functional
      progressions for common multijoint exercises (such as bench press, shoulder
      press, power clean) are presented. Adaptations for periodization are also
      presented for implementation in the rehabilitation sequence. The weight-training
      modifications described in this paper will assist the health professional to
      safely return athletes to the weight room after shoulder injury.

PMID- 9784826
TI  - Critical limits (alert values) for physician notification: universal or medical
      center specific limits?
AB  - The concept of critical limits (alert values), defined as an imminent life
      threatening laboratory result requiring immediate physician notification, has
      been widely adopted as a standard of good laboratory practice. Although virtually
      all laboratories have tests with critical limits, surveys have shown that there
      is no universal alert value list. Recently, nine VA medical centers in the New
      England region, which now constitute one consolidated entity, were surveyed with
      the objective of summarizing critical limits. Universal (100 percent) critical
      limit tests for clinical chemistry were: Calcium; mean low/high, 6.5/12.4 mg/dL:
      Glucose 48/432 mg/dL: Potassium 2.8/6.1 mmol/L: Sodium 121/159 mmol/L. Universal
      hematology tests included: Hematocrit 22.2/59.7 percent: Platelet count 61K/983K:
      white blood count 1.9K/29K. Although there was universal agreement that abnormal
      coagulation tests (PT, PTT) should be included on the hematology critical limit
      list, there was wide variation in the reporting of coagulation tests (seconds and
      INR) and patient therapeutic status (anticoagulant or no-anticoagulant).
      Universal alert values for microbiology were: Positive blood culture: Positive
      cerebral spinal fluid (CSF) culture: Positive CSF Gram stain. There was no
      universal agreement regarding critically high (potentially toxic) therapeutic
      drugs, with two medical centers declining to notify physicians of any abnormally
      high therapeutic drug level. No other qualitative critical limits for other
      laboratory sections, such as physician notification of an unexpected malignancy
      (surgical pathology) were universal. Medical center specific critical limits,
      designed to meet the clinical needs of each facility, are the norm in the nine
      medical centers. Laboratories do need periodically to review their critical limit
      lists with appropriate clinical input to avoid including critical limits for
      laboratory tests not required for urgent physician notification and patient
      evaluation and treatment.

PMID- 9784828
TI  - Factor V inhibitor in a liver transplant patient associated with porcine
      xenoperfusion.
AB  - The development of a high-titer factor V inhibitor is described in a patient who
      underwent orthotopic liver transplantation followed by porcine xenoperfusion
      after an acute rejection episode. The inhibitor showed no cross-reactivity to
      either porcine or bovine factor V, nor was it accessible to human platelet factor
      V. The limitations of treatment modalities including intravenous immunoglobulin,
      steroids, cytotoxic therapy, intense plasmapheresis and platelet transfusions are
      discussed.

PMID- 9784827
TI  - Identification of human immunodeficiency virus-infected individuals by delayed
      type hypersensitivity skin testing.
AB  - OBJECTIVE: To determine if more useful information could be derived from delayed
      type hypersensitivity skin testing of human immunodeficiency virus (HIV)-infected
      patients by measuring the amount of induration in response to skin testing in
      contrast to assessing for the presence of anergy. DESIGN: Prospective, double
      blind trial. SETTING: Two HIV clinics. PATIENTS: A sample of 60 ambulatory, HIV
      infected patients and 18 normal controls. INTERVENTIONS: Delayed type
      hypersensitivity skin testing with a panel of recall antigens. MAIN OUTCOME
      MEASURES: Anergy, total induration in response to the panel of antigens, and CD4
      lymphocyte count. RESULTS: Anergy was present in only 28 of 60 (46.7 percent) HIV
      infected subjects. A low skin test score (under 20 mm of total induration) was
      present in 43 of 60 (71.7 percent) HIV-infected subjects (p < 0.01 vs anergy).
      One control patient was anergic, while two had a low skin test score (p = NS).
      Among HIV-infected subjects, there was poor correlation between CD4 lymphocyte
      count and skin test score (R2 = 0.12). CONCLUSIONS: Skin testing by this method
      identifies more HIV-infected patients than does assessing the presence or absence
      of anergy.

PMID- 9784830
TI  - Lidocaine, quinidine, and theophylline binding to human milk.
AB  - Lidocaine, quinidine, and theophylline binding to normal pooled mature human milk
      was determined using equilibrium dialysis at 4 degrees C. Binding to milk was
      compared with binding to pooled human serum. The observed binding was related to
      the relative lipid solubility of each drug in milk. The potential for the
      excretion of each drug into milk was also evaluated.

PMID- 9784829
TI  - Altered T cell cytokine production following mechanical trauma.
AB  - BACKGROUND: Cell mediated immunity is suppressed following traumatic injury. The
      Objective is to determine whether there is a shift from T helper type 1 (TH1) to
      TH2 cell cytokine production following mechanical trauma in a rat model. METHODS:
      Male Sprague-Dawley rats were anesthetized and subjected to bilateral femur
      fractures or sham injury. Spleens were removed 3 days later. T cell proliferation
      and cytokine production were stimulated by culturing spleen cells with the T cell
      mitogen concanavalin A (con A). Interleukin-2 (IL-2), interferon-gamma (IFN
      gamma), IL-10 and IL-4 concentrations were measured in spleen cell supernatants
      using enzyme linked immunosorbent assays. RESULTS: Con A-induced spleen cell
      proliferation was decreased in traumatized rats compared to controls (p < 0.05).
      Spleen cell supernatant concentrations of the TH1 cytokines IL-2 and IFN-gamma
      were decreased in the trauma group (p < 0.05). Supernatant concentrations of the
      TH2 cytokine IL-10 were also decreased in traumatized rats (p < 0.01). The IL-4
      concentrations were below the detection limit (< 15 pg/mL) in all cell
      supernatants. CONCLUSIONS: Mechanical tissue injury leads to generalized
      suppression of T helper cell cytokine production rather than a shift from TH1 to
      TH2 cell activity. Post-trauma cellular immunosuppression is not mediated via
      excess IL-10 production by TH2 cells.

PMID- 9784831
TI  - Chromosome fragile sites in mentally retarded males: increased incidence with
      seizures and diphenylhydantoin therapy.
AB  - Chromosome fragile site or lesion data were examined in 154 institutionalized
      mentally retarded males with or without seizures or treated with anti-seizure
      medication. Blood lymphocytes were cultured using three different cell culture
      conditions and the incidence of specific chromosome fragile sites (10q25, 16q22,
      and 12q23) or lesions determined. Increased fragile sites were seen in mentally
      retarded males with seizures compared to those without seizures in cells grown in
      folate-deplete Medium 199. Those with seizures and treated with diphenylhydantoin
      had a higher incidence of induced fragile sites (p < 0.001) relative to similar
      patients treated with anti-seizure medication other than diphenylhydantoin. These
      results suggest that a cohort of patients with mental retardation and seizures
      are more likely to have induced cytogenetic changes when treated with
      diphenylhydantoin than mentally retarded individuals without seizures.

PMID- 9784832
TI  - Hereditary hemochromatosis.
AB  - Genetic (hereditary) hemochromatosis is probably the most common autosomal
      recessive disorder found in white Americans, of whom about 5/1,000 (0.5 percent)
      are homozygous for the associated gene. The hemochromatosis gene is probably
      located close to the HLA-A locus on the short arm of chromosome 6. Homozygous
      individuals may develop severe and potentially lethal hemochromatosis, especially
      after age 39. Hereditary hemochromatosis involves an increased rate of iron
      absorption from the gut with subsequent progressive storage of iron in soft
      organs of the body. Excess iron storage eventually produces pituitary,
      pancreatic, cardiac, and liver dysfunction and death may result from cardiac
      arrhythmias, congestive heart failure, and/or hepatic failure or cancer. Early
      diagnosis can prevent these excess iron-induced problems. Iron overload owing to
      HLA-linked hereditary hemochromatosis can be distinguished from other causes of
      hemochromatosis by liver biopsies and interpretations. Patients at risk for
      genetic hemochromatosis should be screened, identified, and treated as early as
      age 20 to prevent or minimize the deadly complications of hemochromatosis.
      Population screening should include measurements of serum iron concentration,
      total iron binding capacity (TIBC), percent saturation of transferrin, and serum
      ferritin concentrations. Family members of hereditary hemochromatosis patients
      are at increased risk and should be tested. Screening, identification and early
      treatment (phlebotomies, sometimes in combination with the use of Desferal or
      other iron-chelating agents) may help prevent or reduce iron-related organ damage
      and premature deaths. Early diagnosis and treatment will reduce the population of
      aging individuals with severe, complicated hemochromatosis and dramatically
      reduce medical costs (billions of U.S. dollars per annum) associated with the
      management of this disease.

PMID- 9784833
TI  - Fluorimetric studies on saccharide binding to the basic lectin from Artocarpus
      hirsuta.
AB  - The binding of Artocarpus hirsuta lectin to galactose and its derivatives was
      examined by fluorescence spectroscopy. The intrinsic fluorescence intensity of
      the lectin was enhanced by 55% upon binding to methyl alpha-galactose without any
      change in the emission maximum (333 nm). 4-Methyl umbellifery alpha
      galactopyranoside showed 100% quenching of its fluorescence intensity upon
      binding to the lectin without any shift in the emission maximum (373 nm). The
      association constant for the binding of the above sugars to the lectin decreases
      with increasing temperature. Methyl group in the alpha anomeric position of
      galactose enhanced the binding while that in the beta position reduced the
      binding to the lectin. Solute quenching studies of the lectin using acrylamide,
      potassium iodide and cesium chloride indicated that the tryptophan residues were
      fully accessible to the neutral quencher, while only partly accessible to the
      ionic quenchers.

PMID- 9784834
TI  - Gene encoding a human testis Sertoli cell component related to LIM domain
      protein.
AB  - The cDNA (HED-2) encoding a 20 kDa protein found in mammalian epididymal fluid
      was isolated from a human testis expression library. It is composed of 1908 bp,
      containing a reading frame of 1479 bp, coding a polypeptide consisting of 493
      amino acids, and assigned the accession number: U15158 by GenBank (Biochem. Mol.
      Biol. Int. 34, 1131-1136, 1994). HED-2 has 99% identity with the zyxin gene in
      amino acid sequence, a component of cell junction matrix and a member of the LIM
      domain protein family. Northern blot analysis of RNAs prepared from various human
      tissues showed that the HED-2 gene was expressed in all tissues analyzed. Sertoli
      cells of human testis expressed the gene as determined by an in situ
      hybridization method. The present study shows that the HED-2 gene is a member of
      the LIM domain protein family.

PMID- 9784836
TI  - Various forms of rabbit plasma alpha-1-antiproteinase.
AB  - Amino acid sequencing of the ficin-derived C-terminal fragments of alpha-1
      antiproteinase (also called alpha-1-antitrypsin or alpha-1-proteinase inhibitor)
      prepared from rabbit plasma revealed the presence of the E isoform, which had
      been confirmed in the cDNA library in addition to the F and S-1 forms. The S-2
      form was identified in inflamed rabbit plasma. The ficin digest of human plasma
      alpha-1-antitrypsin resulted in a major fragment of the M type. Multiple forms of
      alpha-1-antiproteinase in the rabbit plasma implicate the unknown functions other
      than the inhibition of neutrophil elastase.

PMID- 9784835
TI  - Neonatal hyperbilirubinemia and mutation of the bilirubin uridine diphosphate
      glucuronosyltransferase gene: a common missense mutation among Japanese, Koreans
      and Chinese.
AB  - We analyzed the bilirubin uridine diphosphate-glucuronosyltransferase (B-UGT)
      gene in 42 Japanese newborns with hyperbilirubinemia and determined that 21
      infants were heterozygous while 3 was homozygous for Gly71Arg. Allele frequency
      of Gly71Arg was 0.32 in newborns with hyperbilirubinemia, which was significantly
      higher than 0.13 in healthy Japanese controls. This mutant allele is also
      prevalent among Korean and Chinese healthy controls with a frequency of 0.23 in
      both populations. However, this mutation was not detected in 50 healthy German
      controls. These data suggest that the high frequency of the Gly71Arg mutation of
      the B-UGT gene is associated with high incidence of neonatal hyperbilirubinemia
      in Japanese, Korean and Chinese populations.

PMID- 9784838
TI  - Chemical inactivation of bacterial GABA aminotransferase.
AB  - The effects of three potential irreversible inhibitors of gamma-aminobutyrate
      aminotransferase from Pseudomonas fluorescens were studied in order to throw more
      light on the nature of the active site of the enzyme. The thiol group reagent
      mercuric chloride inactivated the enzyme in a concentration-dependent manner.
      Inhibition kinetics were consistent with a simple bimolecular reaction. The
      second-order rate constant was 4.2 x 10(3) +/- 0.61 M-1 sec-1. In contrast to
      either of the substrates, the cofactor pyridoxal 5'-phosphate could protect the
      enzyme from the inhibition, suggesting cysteinyl residues are important for
      cofactor binding at the active site. p-Chloromercuribenzoic acid produced a
      similar inactivation of the enzyme. 4-Amino-2-fluorobutanoic acid also inhibited
      enzymic activity but in this case the inhibition was reversible and competitive
      with respect to gamma-aminobutyric acid (GABA). The inhibitor constant (Ki) was
      0.83 +/- 0.44 mM. We found no evidence that this fluorinated analogue of GABA
      could act as a substrate for the enzyme.

PMID- 9784837
TI  - Reduced level of ATF is correlated with transcriptional repression of DNA
      topoisomerase II alpha gene during TPA-induced differentiation of HL-60 cells.
AB  - DNA topoisomerase II is a marker for the proliferation state of mammalian cells
      in culture, and the protein levels are markedly higher in exponentially growing
      cells than quiescent cells and can be downregulated by growth of the cells at
      high density and serum starvation. Correlation between ATF and TPA-repressed DNA
      topoisomerase II alpha (Topo II alpha) mRNA has been investigated during TPA
      induced differentiation of HL-60 cells. Topo II alpha mRNA and unknotting
      activity were reduced at 24 hours in TPA-treated HL-60 cells. The level of Topo
      II alpha mRNA and the activity were gradually decreased in proportion to the
      concentration of TPA. Two DNA-protein complexes were formed by DNA mobility shift
      assay when ATF-binding site was incubated with nuclear extract prepared from TPA
      free HL-60 cells, and the amount of ATF was vanished after TPA treatment. TPA
      repressed Topo II alpha mRNA and ATF levels were partially restored after
      pretreatment of staurosporin. These results suggest that the reduced level of ATF
      may be important to the transcriptional repression of Topo II alpha gene during
      TPA-induced differentiation in HL-60 cells and related to protein kinase C signal
      pathway.

PMID- 9784839
TI  - Alloxan diabetes regulates adenosine deaminase activity in mice: tissue- and age
      specific correlation.
AB  - Effect of alloxan induced diabetes on the activity of adenosine deaminase (ADA)
      was studied in the liver, spleen, stomach and small intestine of mice at two
      different postnatal ages (preweaned, 15-day and postweaned, 60-day). Alloxan
      significantly stimulates (133%) ADA activity in the liver of 15-day old mice,
      while it has no significant effect in the 60-day old animals. In contrast, ADA
      activity was moderately increased (25%) in spleen of both the ages. However, no
      significant influence of alloxan was observed on ADA activity of stomach at
      either age of mice. On the other hand, alloxan treatment increases (69%)
      intestinal ADA activity in 15-day old mice, with no significant change in 60-day
      old animals. Thus, alloxan diabetes increases ADA activity in an age- and tissue
      specific manner. Stimulation of ADA activity in diabetic mice might play role in
      immune and other metabolic dysfunctions in diabetic conditions.

PMID- 9784840
TI  - Heat stress affects the glucocorticoid receptor interaction with heat shock
      protein Hsp70 in the rat liver.
AB  - The association of glucocorticoid hormones receptor (GR) with heat shock protein
      Hsp70 in the liver cytosol of rats exposed to 41 degrees C whole body
      hyperthermic stress was examined by quantitative immunoblotting of the two
      proteins within immunopurified untransformed GR multiprotein complexes. The
      presence of Hsp70 in the rat liver GR heterocomplexes was confirmed, and 2-fold
      increase in the Hsp70 relative to the steroid binding protein content within the
      complexes was recorded 2 and 12 h after the stress. This increase exceeded the
      stress-induced elevation in the total cytoplasmic Hsp70 level, but could not be
      seen 24 h after the stress, when cytoplasmic Hsp70 returned to basal level. The
      results suggest that hyperthermic stress alters the composition of the rat liver
      untransformed GR heterocomplexes increasing the Hsp70 share.

PMID- 9784841
TI  - Peroxide production and apoptosis in cultured cells carrying mtDNA mutation
      causing encephalomyopathy.
AB  - When cybrids with a point mutation, which locates in the tRNALeu(UUR) gene of
      mtDNA and causes a mitochondrial encephalomyopathy (MELAS syndrome), were exposed
      to a high concentration of oxygen (95%), the peroxide production markedly
      increased by 6 h of oxygen exposure, whereas the peroxide production was similar
      among the cybrids under a normal concentration of oxygen. The peroxide production
      by oxygen exposure was enhanced particularly in cybrids with high proportions of
      the mutant mtDNA and low respiratory capacities. The appearance of apoptotic
      cells by oxygen exposure was high in cybrids with the impaired respiratory
      function due to the mutation. An antioxidant NAC successfully suppressed both the
      peroxide production and apoptosis. These results imply that the peroxide
      production plays an important role in inducing apoptosis in cells carrying the
      mtDNA mutation causing encephalomyopathy.

PMID- 9784842
TI  - Purification of heparin-binding protein HBp17 and identification of HBp17 heparin
      binding site.
AB  - HBp17 was purified by Heparin-Copper biaffinity chromatography and HPLC from
      conditioned medium of A431 cell. The purified HBp17 was digested by
      staphylococcus urcus V8 protease or chymotrypsin and the heparin-binding
      fragments were isolated by Heparin-Sepharose. One binding site of peptide mapping
      is HBp17 residues 110-145 produced by V8. Another one is HBp17 residues 82-143
      which were produced by chymotrypsin digestion. Two binding sites of peptide
      mapping are overlap. Therefore the residues 110-143 of HBp17 are the principle
      heparin binding site. The basic amino acid cluster in this region may be
      contribute to the binding of HBp17 to heparin or heparan sulfate proteoglycan on
      the cell surface and extracellular matrix.

PMID- 9784843
TI  - EPC-K1 attenuates peroxynitrite-induced apoptosis in cerebellar granule cells.
AB  - Apoptosis induced by peroxynitrite in cultured cerebellar granule cells was
      confirmed morphologically by chromatin condensation and biochemically by DNA
      laddering. A 30 min exposure to peroxynitrite (10 microM) initiated oxidative
      stress, which caused the formation of thiobarbituric acid-reactive substances
      (TBARS) and the alteration of cell membrane fluidity. Peroxynitrite treatment
      also caused ATP decrease and thus activated the apoptotic program. Pre-treating
      cells with antioxidant EPC-K1 (L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl
      2-(4,8,12-trimethyltridecyl)-2H -1- benzopyran-6-yl-hydrogen phosphate] potasium
      salt), a new water-soluble derivative of vitamin C and vitamin E, attenuated
      oxidative injury and prevents cells from apoptosis. The results suggest that EPC
      K1 might be used as a potential therapeutic agent for diseases associated with
      NO/ONOO(-)-mediated neuronal injury.

PMID- 9784844
TI  - The beta subunit of chloroplast ATP synthase (CF0CF1-ATPase) is phosphorylated by
      casein kinase II.
AB  - We studied a phosphate acceptor for casein kinase II (CK-II) in chloroplasts, and
      found a 56 kDa protein (p56) as an acceptor, which was partially purified from
      the stroma of spinach chloroplasts. The N-terminal amino acid sequence of p56 was
      identical with that of the beta subunit of chloroplast ATP synthase (CF0CF1
      ATPase). In addition, the recombinant beta subunit of CF1 was phosphorylated when
      the subunit was incubated with CK-II. These results suggest that the beta subunit
      of CF1 is a substrate protein of CK-II in the chloroplast.

PMID- 9784845
TI  - Purification and characterization of sucrose synthase isozymes from etiolated
      rice seedlings.
AB  - Presence of homo- and hetero-tetrameric rice sucrose synthase (RSS) isoforms in
      etiolated rice seedlings was demonstrated by immunoprecipitation using
      monospecific antibodies. Three RSS isozymes with various pI values were purified
      by ammonium sulfate fractionation, Sepharose CL-6B gel filtration, DEAE-Sephacel
      and Mono-Q ion exchange chromatographies. They were characterized as
      heterotetramers composed of RSS1 and RSS2 subunits. All of them used UDP as the
      best substrate. The presence of divalent metal ions increased the activities of
      synthesis but inhibited the cleavage of sucrose.

PMID- 9784846
TI  - Thiamine triphosphatase activity in bovine kidney.
AB  - Properties of soluble thiamine triphosphatase (ThTPase), adenosine
      triphosphatase, nucleoside triphosphatase and alkaline phosphatase activities in
      bovine kidney were compared. ThTPase and the other phosphatases differed clearly
      in their pH-dependences, K(m) and molecular masses. Apparent K(m) and pH optimum
      for ThTPase were determined to be 45.5 microM and 8.9, respectively. Molecular
      mass of the enzyme was 29.1 kDa as estimated by Sephadex G-100 gel filtration.
      The results obtained show bovine kidney to contain a specific soluble ThTPase,
      this enzyme being the only one hydrolyzing low concentrations of ThTP.

PMID- 9784847
TI  - Analysis of glycosphingolipids of human head and neck carcinomas with comparison
      to normal tissue.
AB  - Glycosphingolipids of head and neck carcinomas from six tumor-bearing patients
      were analyzed and compared to those of normal tissue from similar areas. The
      total glycosphingolipid content and the lipid-bound sialic acid were much higher
      in carcinomas than in normal tissue. Major neutral glycolipids were
      glucosylceramide, lactosylceramide, trihexosylceramide and paragloboside.
      Sulfatides were seen only in extracts from normal tissue which also showed a
      rather simple ganglioside pattern with #GM3 and GD3 as major species, whereas
      tumors showed additional species such as GM2 and GD2, along with a strong
      increase in LM1, GM1, GD1a and GT1b.

PMID- 9784848
TI  - Enhancement of hydroxyl radical generation in the Fenton reaction by alpha
      hydroxy acid.
AB  - The effect of various organic acids on hydroxyl radical (.OH) generation in the
      Fenton reaction were examined by the ESR spin trapping technique, where 5,5
      dimethyl-1-pyroline-N-nitroxide (DMPO) and alpha-phenyl-tert-butyl nitrone (PBN)
      were used as the spin trapping reagents. alpha-Hydroxy acids such as lactic acid,
      glycolic acid and 2-hydroxy isobutyric acid were found to markedly enhance .OH
      generation in the reaction. In contrast, beta-hydroxy acid, alpha-keto acid,
      esters of alpha-hydroxy acids, aldehydes and other straight chain organic acids
      had no such enhancing activity. alpha-Amino acids had also no enhancing effect.
      The results suggest that the alpha-hydroxy acid moiety is prerequisite for the
      enhancement of .OH generation in the Fenton reaction. Superoxide dismutase did
      not inhibit the enhancing effect of alpha-hydroxy acids whereas catalase
      completely inhibited the .OH generation. Thus, alpha-hydroxy acids directly
      enhanced the .OH generation via the Fenton reaction but not the Haber-Weiss
      reaction. Possible role of lactic acid manipulating .OH generation is discussed
      in relation to the ischemia-reperfusion cell damage.

PMID- 9784849
TI  - Sulphydryl groups and their relation to the antioxidant enzymes of chelonian red
      blood cells.
AB  - Thiol groups of hemoglobin and blood glutathione are higher in Geochelone
      carbonaria than in Geochelone denticulata. Exposure of stripped hemolysate of
      both tortoises to terc-butyl hydroperoxide, resulted in a higher ferroheme
      oxidation of G. denticulata hemoglobin. In this example glutathione reductase and
      glutathione peroxidase, were not active due to the absence of GSH and NADPH,
      suggesting that the thiol groups of G. carbonaria hemoglobin act as antioxidant,
      similar to GSH. In the total hemolysate, however, where the antioxidant enzymes
      are active, both species showed similar levels of hemoglobin oxidation,
      suggesting that the protective effect of thiol groups of hemoglobin are less
      effective for heme protection. The activity of glutathione reductase and
      glutathione peroxidase was higher in erythrocytes of G. denticulata and the
      activity of catalase and superoxide dismutase was higher in erythrocytes of G.
      carbonaria.

PMID- 9784850
TI  - Effects of eicosapentaenoic acid and its 15-hydroperoxy and 15-hydroxy
      derivatives on glucosamine synthetase activity in rabbit gastric mucosa.
AB  - The effects of eicosapentaenoic acid and its 15-hydroperoxy and 15-hydroxy
      adducts on the activity of glucosamine synthetase, the rate-limiting enzyme of
      mucus synthesis, in rabbit gastric antral mucosa were examined. 15-Hydroperoxy
      eicosapentaenoic acid inhibited the glucosamine synthetase activity at
      concentrations of 10, 20 and 50 microM. The effect was concentration-dependent,
      and the concentration required for 50% inhibition was approximately 20 microM.
      Eicosapentaenoic acid and its 15-hydroxy adduct had no significant effect on the
      enzyme activity at the same concentration range. The experiment utilizing Fe2+
      revealed that the inhibitory effect of 15-hydroperoxyeicosapentaenoic acid on the
      glucosamine synthetase activity is not due to hydroxy radical which is expected
      to be formed from the hydroperoxy adduct. These results suggest that 15
      hydroperoxyeicosapentaenoic acid has the potential to reduce the synthesis of
      gastric mucus by inhibiting the glucosamine synthetase activity.

PMID- 9784851
TI  - Inhibitory effects by a submandibular gland extract on luteinizing hormone
      stimulated testosterone production by testicular cells.
AB  - In order to evaluate the role of the submandibular gland (SMG) on testosterone
      (T) production by the testis, primary cultured testicular cells were prepared
      from rats that had the submandibular gland surgically ablated (G-) and control
      (sham operated) rats (S.O.) respectively. The cells were incubated with or
      without 100 ng/ml luteinizing hormone (LH) and/or SMG extract. The same linear
      increase in T secretion was shown by both S.O. and G- cells on multi-stimulation
      with LH for up to 96 hrs. However, while an equivalent response was shown for
      S.O. cells after a single LH stimulation at 96 hrs, T secretion by the G- cells
      reached a plateau after 24 hrs. The level at 96 hrs was thus approximate 30% and
      33% of those of S.O. cells with and without multi-stimulus by LH for 96 hrs,
      respectively. When S.O. cells were cultured with SMG extract, LH-stimulated T
      secretion was dose-dependently inhibited and there was no effect on basal T
      secretion. The inhibitory effect was abolished by treatment at 95 degrees C for 5
      min. Ultra-filtration indicated that the molecular size of the inhibitory agent
      was greater than 30,000. It is proposed that SMG may contain a high molecular
      weight, heat labile soluble factor(s) which affects T secretion by inhibiting LH
      action in testicular cells.

PMID- 9784852
TI  - Seroconversion of type B to O erythrocytes using recombinant Glycine max alpha-D
      galactosidase.
AB  - Recombinant alpha-D-galactosidase (rGal) from soybean (Glycine max) hydrolyzed
      the immunodominant alpha-D-galactose residue from the B epitope of red blood
      cells. This converted type B erythrocytes to type O which are "universally"
      transfusable. Type B red blood cells were obtained from four different donors and
      enzymatically converted. Cell function parameters, including red cell indices,
      pH, methemoglobin, carboxyhemoglobin, osmotic fragility, hemolysis, 2,3
      diphosphoglycerate, cholinesterase, ATP, and antigen typing of treated cells were
      compared to controls. These pilot studies indicate that rGal could have potential
      biotechnical application in the production of universally transfusable red blood
      cells.

PMID- 9784853
TI  - Insulin rapidly induces nuclear translocation of PI3-kinase in HepG2 cells.
AB  - Insulin action on nuclear PI3-Kinase and IRS-1 was explored in HepG2 cells.
      Following insulin treatment, the cells were subjected to subcellular
      fractionation. Western blot analyses were carried out to identify IRS-1 and PI3
      Kinase in the nuclear and postnuclear preparations. IRS-1 protein was identified
      in the nucleus under basal condition. Insulin had no effect in the content of
      nuclear IRS-1. In contrast, PI3-Kinase was not detected under basal condition.
      However, insulin treatment for 1 to 10 min caused significant increase of PI3
      Kinase in the nucleus while it induced corresponding decrease of PI3-Kinase in
      cytoplasm. Strikingly, Insulin stimulated the association of IRS-1 and PI3-Kinase
      in the nucleus in a similar kinetics with the nuclear translocation of PI3
      Kinase. These results suggest that insulin induces nuclear translocation of PI3
      Kinase and the translocated PI3-Kinase associates with nuclear IRS-1. The
      association of IRS-1 and PI3-Kinase in the nucleus in response to insulin may
      play important roles in nuclear insulin actions.

PMID- 9784854
TI  - Purification and characterization of a soluble form of lysosome-associated
      membrane glycoprotein-2 (lamp-2) from rat liver lysosomal contents.
AB  - Lysosomal membrane of rat liver contains a highly glycosylated protein referred
      to as lamp-2. Lamp-2 occurs to a significant extent in a soluble fraction of rat
      liver lysosomes. The soluble form of lamp-2 (SF-lamp-2) was purified to
      electrophoretic homogeneity. An apparent molecular weight M(r) of SF-lamp-2 on
      sodium dodecy sulfate-polyacrylamide gel electrophoresis was determined to be
      91,000 which is 5,000 less than that of the membranous form of lamp-2 (MF-lamp
      2). SF- and MF-lamp-2 were very similar to each other in terms of sialic acid
      content, NH2-terminal amino acid sequence and isoelectric point. Gel filtration
      data indicated that native SF-lamp-2 has an M(r) = 360,000. Taken together, SF
      lamp-2 forms a tetrameric structure consisting of a homogenous polypeptide
      lacking a membrane-spanning domain and a cytoplasmic tail near the COOH-terminus.

PMID- 9784855
TI  - Oxygen free-radicals mediate the damaging effect of ultraviolet light on membrane
      mitochondria.
AB  - This paper reports evidence that exposure of mitochondria to near-ultraviolet
      light inhibits electron transport, collapses the electric gradient, and increases
      non-specific membrane permeability to matrix solutes such as Ca2+. Membrane
      energization, as well as superoxide dismutase and catalase avoid membrane
      leakiness. Increased permeability correlates with a diminution in the titrated
      thiol groups. Plausibly the pore is formed through the formation of sulfhydryl
      bridges by the action of UV light-derived oxygen-centered free- radicals on
      membrane proteins.

PMID- 9784856
TI  - Chemical genetics resulting from a passion for synthetic organic chemistry.

PMID- 9784857
TI  - Synthesis and biological evaluation of aeroplysinin analogues: a new class of
      receptor tyrosine kinase inhibitors.
AB  - Receptor tyrosine kinases (RTKs), such as the epidermal growth factor receptor
      (EGFR) and the platelet-derived growth factor receptor (PDGFR), are critically
      involved in the transduction of mitogenic signals across the plasma membrane and
      therefore in the regulation of cell growth and proliferation. Enhanced RTK
      activity is associated with proliferative diseases such as cancer, psoriasis and
      atherosclerosis, while decreased function may be associated for instance with
      diabetes. EGFR and PDGFR are selectively inhibited by analogues of the marine
      natural product aeroplysinin. The synthetic inhibitors display IC50 values in the
      low micromolar range and in contrast to the natural product show pronounced
      inhibitory activity in cultured cells in vivo. The mechanism of inhibition is
      likely based on a covalent modification of the target enzymes by reaction of
      epoxy ketone 8 with various nucleophiles.

PMID- 9784858
TI  - Synthetic analogues of TNP-470 and ovalicin reveal a common molecular basis for
      inhibition of angiogenesis and immunosuppression.
AB  - TNP-470 (1), a synthetic derivative of the natural product fumagillin (2),
      potently inhibits angiogenesis in vivo and the growth of endothelial cell
      cultures in vitro. The structurally related natural product ovalicin (3) also
      inhibits angiogenesis but possesses potent immunosuppressive activity. The recent
      finding that all three drugs bind and inhibit the same target, methionine
      aminopeptidase 2 (MetAP2), raised the question of whether TNP-470 is also
      immunosuppressive and whether inhibition of MetAP2 underlies both activities of
      ovalicin. To address these questions, we synthesized a series of analogues of TNP
      470 and ovalicin and tested them for their abilities to inhibit the proliferation
      of either endothelial cell or mixed lymphocyte cultures. TNP-470 and its
      analogues were found to possess both immunosuppressive and anti-angiogenic
      activities. A strong correlation was observed between the ability of compounds to
      inhibit bovine and human endothelial cell growth and their ability to inhibit the
      mouse mixed lymphocyte reaction (MLR), implying that the two activities share a
      common molecular basis, i.e., inhibition of MetAP2. Interestingly, ovalicin and
      several other compounds behaved differently in the human MLR than in either the
      mouse MLR or human endothelial cell proliferation assays, pointing to possible
      species-specific and cell type-specific differences in the metabolism or uptake
      of these compounds.

PMID- 9784860
TI  - An efficient substitution reaction for the preparation of thyroid hormone
      analogues.
AB  - The substitution of the sterically hindered carbon of the potent thyroid hormone
      agonist, GC-1, was effected by a reaction based on the solvolysis of the benzylic
      hydroxyl group. The reaction was found to proceed in high yield with a variety of
      nucleophiles including alcohols, thiols, allyl silanes and electron-rich aromatic
      compounds, providing a convenient route to the synthesis of new thyroid hormone
      analogues.

PMID- 9784859
TI  - Precursor-directed biosynthesis of 12-ethyl erythromycin.
AB  - A precursor-directed method for the biosynthesis of novel 6-deoxyerythronolide B
      derivatives has been extended to allow alteration of the functionality at C-12.
      We recently described a simple and practical method for harnessing the
      biosynthetic potential of the erythromycin pathway to generate novel molecules of
      natural product-like complexity by feeding designed synthetic molecules to an
      engineered mutant strain having an altered 6-deoxyerythronolide B synthase
      (DEBS). Our initial applications of this technique focused on alteration of the
      ethyl side chain of 6-dEB (C14-C15). We now report the extension of this approach
      to modification of the C-12 substituent. An appropriately designed substrate is
      shown to incorporate into 6-dEB biosynthesis, yielding a 6-dEB analogue bearing a
      12-ethyl group. This 6-dEB analogue is a substrate for post-polyketide tailoring
      enzymes, and is converted into the corresponding analogue of erythromycin C.
      These results show that many of the downstream active sites are tolerant of this
      unnatural functionality and suggest that a wide variety of erythromycin
      derivatives should be accessible by this approach or by total biosynthesis via
      genetic engineering.

PMID- 9784862
TI  - Eponemycin analogues: syntheses and use as probes of angiogenesis.
AB  - Derivatives of the epoxy-beta-aminoketone containing natural product eponemycin
      have been prepared in order to study the molecular mode of action of this anti
      angiogenic compound. Synthesis and use of a biotinylated dihydroeponemycin
      analogue demonstrated that dihydroeponemycin forms a covalent adduct with at
      least two intracellular proteins in human endothelial cells. Pretreatment of
      cells with a five equivalent excess of dihydroeponemycin precluded biotin
      dihydroeponemycin binding indicating a specific interaction between natural
      product and the target proteins. This biotin-dihydroeponemycin derivative will
      prove useful in the purification and identification of eponemycin receptors.

PMID- 9784861
TI  - Design, synthesis and biological evaluation of nonpeptide integrin antagonists.
AB  - Recent studies demonstrated that peptide and antibody antagonists of integrin
      alpha v beta 3 block angiogenesis and tumor growth. In this article, the design,
      synthesis and biological evaluation of a series of nitroaryl ether-based,
      nonpeptide mimetics are described. The design of these compounds was based on
      Merck's arylether/alpha-aminoacid/guanidine framework and incorporates a novel
      nitroaryl system. The synthesized mimetics were tested against a variety of
      integrins (alpha v beta 3, alpha IIb beta 3, and alpha v beta 5) in order to
      determine their binding selectivity and ability to inhibit cell adhesion.
      Selected compounds were also tested for their ability to inhibit angiogenesis in
      vivo in the CAM (chick chorioallantoic membrane) assay. From the generated
      compound library, compounds 16 and 19 proved to be potent and selective
      inhibitors of alpha IIb beta 3 (IC50 = 14 nM) whereas compound 11 showed
      excellent in vivo inhibition of angiogenesis (at 30 micrograms/embryo).

PMID- 9784863
TI  - A molecular gate which controls unnatural ATP analogue recognition by the
      tyrosine kinase v-Src.
AB  - Engineered proteins with specificity for unnatural substrates or ligands are
      useful tools for studying or manipulating complex biological systems. We have
      engineered the prototypical tyrosine kinase v-Src to accept an unnatural ATP
      analogue N6-(benzyl) ATP in order to identify v-Src's direct cellular substrates.
      Here we have used molecular modeling to analyze the binding mode of N6-(benzyl)
      ATP. Based on this modeling we proposed that a new ATP analogue (N6-(2-phenethyl)
      ATP might be a better substrate than N6-(benzyl) ATP for the I338G mutant of v
      Src. In fact the newly proposed analogue (N6-(2-phenethyl) ATP is a somewhat
      improved substrate for the engineered kinase (kcat = 0.6 min-1, KM = 8 microM).
      We also synthesized and screened three analogues of N6-(benzyl) ATP: N6-(2
      methylbenzyl), ATP N6-(3-methylbenzyl), and ATP N6-(4-methylbenzyl) ATP to
      further probe the dimensions and shape of the introduced pocket. Results from
      screening newly synthesized ATP analogues agreed well with our modeling
      predictions. We conclude that rather than engineering a 'new' pocket by mutation
      of Ile 338 in v-Src to the smaller Ala or Gly residues, the I338G and I338A
      mutants possess a 'path' for the N6 substituent on ATP to gain access to an
      existing pocket in the ATP binding site. We expect to be able to extend the
      engineering of v-Src's ATP specificity to other kinase families based on our
      understanding of the binding modes of ATP analogues to engineered kinases.

PMID- 9784864
TI  - Photoaffinity study of the cellular interactions of ilimaquinone.
AB  - The marine sponge metabolite ilimaquinone (1) displays a broad range of
      biological activities. To better understand the effects of this natural product,
      a photoaffinity analogue was synthesized and used to probe the cellular
      interactions of ilimaquinone. Irradiation of photoaffinity probe 5 with liver
      cytosol in the presence and absence of excess competitive inhibitor 2 suggests
      that S-adenosylhomocysteinase is an important intracellular target of
      ilimaquinone.

PMID- 9784865
TI  - Biomimetic Diels-Alder cyclizations for the construction of the brevianamide,
      paraherquamide, sclerotamide, asperparaline and VM55599 ring systems.
AB  - A potentially bio-mimetic Diels-Alder cyclization to construct the bicyclo[2.2.2]
      ring system common to the paraherquamides, marcfortines, sclerotamides,
      brevianamides, VM55599, and asperparaline is reported. Epi-deoxybrevianamide E
      (22) is converted into the corresponding lactim ether (23) and then oxidized with
      DDQ to provide an azadiene (24) which is tautomerized in the presence of base to
      azadiene 25 which, spontaneously cyclizes to give a 2:1 mixture of cycloadducts
      26 and 27. These cycloadducts are each in turn, converted into D,L-C-19-epi
      brevianamide A (20) and D,L-brevianamide B (6). The stereochemical implications
      of the [4 + 2] cycloaddition is discussed in the context of a working hypothesis
      on the biosynthesis of this family, particularly VM55599.

PMID- 9784866
TI  - Total synthesis and stereochemistry of cytoblastin.
AB  - The first total synthesis and stereochemical assignment of cytoblastin were
      reported. Key steps included the palladium-mediated coupling of N-SEM-7
      bromoindolactam V ((-)-11) with allylstannane c-13, and osmium tetroxide-mediated
      dihydroxylation of 14, both of which were stereoselective. The stereochemistry of
      cytoblastin was determined as 1A via spectroscopic analysis of the pentacyclic
      derivative 21 of cytoblastin. A connection was then made between the
      stereochemistry so elucidated and the Kishi/Rando hypothesis for the structural
      correlation between (S)-1,2-diacylglycerol and tumor promoters for the process of
      protein kinase C activation.

PMID- 9784868
TI  - A metathetical cycloaddition-cycloreversion approach to the formation of furan
      scaffold libraries.
AB  - A general cycloaddition-cycloreversion metathesis procedure for the selective
      formation of a furan-based template-directed scaffold is described. In addition,
      features relative to library construction, such as the chemoselective nature of
      dipole formation, are discussed. Through the investigation of the temperature
      sensitive cleavage step, the furan synthesis was found to be accelerated by
      aqueous medium at physiological temperature leading to pure product from the
      solid-phase under biologically relevant conditions. The chemoselective nature of
      the rhodium(II) mediated cycloaddition allowed the selective formation of a key
      dipole intermediate, in the presence of a number of carbeneactive functional
      groups, to facilitate the split-pool combinatorial synthesis of a small library
      of compounds.

PMID- 9784867
TI  - Synthesis and inhibitory action on HMG-CoA synthase of racemic and optically
      active oxetan-2-ones (beta-lactones).
AB  - A homologous series of both C3-unsubstituted and C3-methyl substituted oxetan-2
      ones (beta-lactones) was investigated as potential inhibitors of yeast 3-hydroxy
      3-methylglutaryl-coenzyme A (HMG-CoA) synthase. Several reported methods for
      racemic beta-lactone synthesis were studied for preparation of the target series.
      In addition, a novel aluminum-based Lewis acid obtained by combination of Et2AlCl
      with (1R,2R)-2-[(diphenyl)hydroxymethyl] cyclohexan-1-ol was studied for the
      asymmetric [2 + 2] cycloaddition of aldehydes and trimethylsilylketene. This
      Lewis acid exhibited good reactivity but variable enantioselectivity (22-85% ee).
      In in vitro assays using both native and recombinant HMG-CoA synthase from
      Saccharomyces cerevisiae, oxetan-2-ones mono-substituted at C4 with linear alkyl
      chains gave IC50s that decreased monotonically with chain length up to 10 carbons
      and then rose rapidly for longer chains. The trans isomers of 3-methyl-4-alkyl
      oxetan-2-ones showed a similar trend but had 1.3- to 5.6-fold lower IC50s. The
      results imply a substantial hydrophobic pocket in this enzyme that interacts with
      both C-3 and C-4 substituents of oxetan-2-one inhibitors.

PMID- 9784869
TI  - The synthesis and enzymatic incorporation of sialic acid derivatives for use as
      tools to study the structure, activity, and inhibition of glycoproteins and other
      glycoconjugates.
AB  - Methods have been developed for the enzymatic synthesis of complex carbohydrates
      and glycoproteins containing in the sialic acid moiety the heavy metal mercury or
      the transition-state analog phosphonate of the influenza C 9-O-acetyl-neuraminic
      acid esterase-catalyzed reaction. 5-Acetamido-3, 5-dideoxy-9-methylphosphono-beta
      D-glycero-D-galacto-nonulopyra nosidonic acid (1), 5-acetamido-3,5-dideoxy-9
      methylphosphono-2-propyl-alpha-D- glycero-D-galacto-nonulopyranosidonic acid
      triethylammonium salt (2), and 5-acetamido-9-thiomethylmercuric-3, 5,9-trideoxy
      beta-D-glycero-D-galacto-nonulopyranosidonic acid (3) were synthesized. Compounds
      1 and 2 are proposed transition state inhibitors of an esterase vital for the
      binding and infection of influenza C. Compound 3 was enzymatically incorporated
      into an oligosaccharide and a non-natural glycoprotein for use as an aid in the
      structure determination of these compounds by X-ray crystallography.

PMID- 9784870
TI  - Glycoprotein-inspired materials promote the proteolytic release of cell surface L
      selectin.
AB  - The proteolytic release, or shedding, of a cell surface protein can serve a
      regulatory role; the process liberates a soluble form of the protein into
      circulation while downregulating its cell surface concentration. The
      characteristics that render a protein susceptible to proteolytic cleavage are not
      known. We hypothesized that the clustering of a protein at the cell surface might
      target it for proteolysis. To test this hypothesis, we synthesized molecules that
      display multiple copies of sulfated galactose residues, termed neoglycopolymers,
      that are designed to mimic natural ligands for the cell adhesion protein L
      selectin. We found that treatment of human neutrophils with the neoglycopolymers
      resulted in a dose-dependent loss of L-selectin from the cell surface, while
      monovalent compounds and unsulfated neoglycopolymers had no effect. Because L
      selectin is an important mediator in the inflammatory response, such compounds
      could lead to novel antiinflammatory drugs. Moreover, molecules that control
      receptor shedding can be used to alter cellular responsiveness to specific
      ligands or to promote responses at distal sites; consequently, these results have
      broad implications for regulating the location and presentation of important
      biomolecules.

PMID- 9784871
TI  - Protein cross-linking mediated by metalloporphyrins.
AB  - A biomimetic protein cross-linking reaction is described which employs
      oxidatively-activated manganese and iron porphyrins as the reactive species. A
      wide range of proteins cross-link under these conditions, but only if they are
      intimately associated in solution. The reaction is rapid, efficient, and will be
      useful for the suprastructural analysis of multiprotein complexes.

PMID- 9784872
TI  - Synthesis and activity of bivalent FKBP12 ligands for the regulated dimerization
      of proteins.
AB  - The total synthesis and in vitro activities of a series of chemical inducers of
      dimerization (CIDs) is described. The use of small-molecule CIDs to control the
      dimerization of engineered FKBP12-containing fusion proteins has been
      demonstrated to have broad utility in biological research as well as potential
      medical applications in gene and cell therapies. The facility and flexibility of
      preparation make this new class of wholly synthetic compounds exceptionally
      versatile tools for the study of intracellular signaling events mediated by
      protein-protein interactions or protein localization. While some congeners
      possess potency comparable to or better than the first generation natural product
      derived CID, FK1012, structure-activity relationships are complex and underscore
      the need for application-specific compound optimizations.

PMID- 9784873
TI  - Synthesis of a 3-deoxy-L-iduronic acid containing heparin pentasaccharide to
      probe the conformation of the antithrombin III binding sequence.
AB  - We report in this work the total synthesis of a close analogue of the
      pentasaccharide active site of heparin, in which the L-iduronic acid residue has
      been deoxygenated at position three. 1H NMR studies demonstrated that, as
      anticipated, such a modification induces a shift of the conformational
      equilibrium toward 1C4 (contribution to the conformational equilibrium rises from
      37% to 65%) and a substantial decrease of the affinity for antithrombin III (Kd
      0.154 microM versus 0.050 microM).

PMID- 9784874
TI  - Higher order iminodiacetic acid libraries for probing protein-protein
      interactions.
AB  - Full details of the preparation of iminodiacetic acid diamide dimer (2040
      compounds), trimer (560 compounds), and tetramer (1596 compounds) libraries by
      multistep convergent solution-phase synthesis for studying protein-protein
      interactions are provided. The libraries were assembled in a format providing
      small 8-10 compound mixtures and the deconvolution of many of the small mixtures
      to identify screening leads by resynthesis of the individual components have been
      conducted for 320 of the individual compounds to date. A representative example
      of the subsequent exploration of the structure-activity relationships for an
      identified receptor binding antagonist (200 additional individual compounds) and
      steps taken for potential elaboration to a receptor dimerization agonist are
      defined with preparation of representative linked dimers (70 compounds).

PMID- 9784875
TI  - Synthesis, biological activity, and conformational studies of insect allatostatin
      neuropeptide analogues incorporating turn-promoting moieties.
AB  - Allatostatins are 6-18 amino acid peptides synthezed by insects to control
      production of juvenile hormones, which in turn regulate functions including
      metamorphosis and egg production. Four insect allatostatin neuropeptide analogues
      incorporating turn-promoting pseudopeptide moieties in the region responsible for
      biological activity were prepared by solid phase peptide synthetic methods.
      Bioassay indicated that activities approached those of the natural neuropeptides,
      and molecular models based on NMR data showed similar conformations and the
      presence of a beta-turn in the active core region for the four analogues.
      Differences in activity are believed to be due to differences in bulk and
      relative position of atoms in the unnatural portion of the analogues, and their
      differing degrees of conformational freedom. The studies support the feasibility
      of development of neuropeptide-based insect control agents resistant to peptidase
      deactivation.

PMID- 9784876
TI  - Discovering transthyretin amyloid fibril inhibitors by limited screening.
AB  - Insoluble protein fibrils, resulting from the self-assembly of a conformational
      intermediate are implicated to be the causative agent in several human amyloid
      diseases including familial amyloid polyneuropathy (FAP) and senile systemic
      amyloidosis (SSA). These diseases are associated with transthyretin (TTR) amyloid
      fibrils, which appear to form in the acidic partial denaturing environment of a
      lysosome or endosome. Here we identify several structural classes of small
      molecules that are capable of inhibiting the TTR conformational changes
      facilitating amyloid fibril formation. A small molecule inhibitor that stabilizes
      the normal conformation of a protein is desirable as a promising approach to
      treat amyloid diseases and to rigorously test the amyloid hypothesis, the
      apparent causative role of amyloid fibrils in amyloid disease.

PMID- 9784877
TI  - [Interaction of apolipoprotein A1 with phospholipids and structure of mixed
      micelles].
AB  - The structural features of apolipoprotein A1 (apoA1) that provide for the
      formation of its stable micellar complexes with phosphatidylcholine are
      discussed. The results of studies on the secondary structure and functional
      properties of separate sites of the apoA1 polypeptide chain are analyzed. The
      preparation procedures for discoidal micellar complexes of apoA1 with
      phosphatidylcholine are discussed, and the characteristics of the complexes are
      described. The surface activity of apoA1 incorporated into the micellar complexes
      is characterized, and the recombination mechanisms of lipid-protein micelles in
      model systems are discussed. The data discussed indicate that all currently known
      structural-functional properties of apoA1 and its involvement in metabolic and
      physiological processes are completely determined by the surface activity of the
      amphiphilic fragments of its conformationally labile polypeptide chain.

PMID- 9784878
TI  - [Structural organization of 2C-terminal region and its analogs in a subunit of
      ribonucleotide reductase from herpes virus].
AB  - By means of conformational analysis, the spatial structure and conformational
      potential of the H-Tyr-Ala-Gly-Ala-Val-Val-Asn-Asp-Leu-OH molecule, which
      corresponds to sequence 329-337 of the subunit 2 C-terminal region of the herpes
      virus ribonucleotide reductase, were studied. It was shown that its spatial
      organization can be described by a set of 17 low-energy conformations of the
      backbone. The "reverse conformational problem" for this molecule was solved to
      enable the prediction of a series of synthetic analogues matching the set of low
      energy, potentially physiologically active conformations.

PMID- 9784879
TI  - [Comparative analysis of interaction sites of Thermus thermophilus and
      Escherichia coli tRNA(Tyr) with homologous aminoacyl-tRNA synthetases by means of
      chemical modification and nuclease hydrolysis].
AB  - A nucleotide sequence of tRNA(Tyr) from the extreme thermophile Thermus
      thermophilus HB-27 living at 75 degrees C was determined. It is 86 nt long and
      shares a 52% homology with tRNA(Tyr) from Escherichia coli. A comparative
      analysis of the interaction sites of tRNA(Tyr) from T. thermophilus and E. coli
      with the cognate aminoacyl-tRNA synthetases was accomplished by the chemical
      modification and nuclease hydrolysis approaches. The tRNA(Tyr) was shown to
      interact with the cognate enzyme in the anticodon stem (on the 5'-side), in the
      anticodon, in the variable stem and loop (on the 5'-side), and in the acceptor
      stem (on the 3'-side). These regions are located in the variable stem of the L
      form. It was demonstrated that, upon forming the complex E. coli tRNA(Tyr)
      cognate synthetase, endonuclease V1 induces additional cleavages of
      phosphodiester bonds on the 3'-side of the anticodon stem and on the 5'-side of
      the T-stem. This implies that tRNA may change its conformation when it interacts
      with the enzyme.

PMID- 9784880
TI  - [Synthesis of oligosaccharides related to HNK-1 antigen. 2. Synthesis of 3'''-O
      (3-O-sulfo-beta-D-glucuronopyranosyl)-lacto-N-neotetrao se beta-propylglycoside].
AB  - A derivative of allyl 3"-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-beta
      lactoside with a free OH group at C-4GlcNAc was glycosylated with
      trichloroacetimidate of selectively protected GlcA(beta 1-->3)Gal alpha
      disaccharide in dichloromethane in the presence of trimethylsilyl triflate
      resulting in a pentasaccharide product with an 82% yield. This product was
      converted to monohydroxy derivative with a free OH group at C-3GlcA via the
      formation and the subsequent opening of the 6,3-lactone ring in the glucuronic
      acid residue. The 3"'-O-sulfation of the monohydroxy derivative, the removal of
      the protective groups, and the reduction of the allyl aglycon yielded the
      pentasaccharide propyl glycoside NaSO3-3GlcA(beta 1-->3)Gal(beta 1-
      >4)GlcNAc(beta 1-->3)Gal(beta 1-->4)Glc beta-Opr comprising the oligosaccharide
      chain of the SGGL-1 glycolipid, which is recognized by HNK-1 antibodies. NaSO3
      3GlcA(beta 1--> 3)Gal beta OAll, GlcA(beta 1-->3)Gal(beta 1-->4)GlcNAc(beta 1-
      >3)Gal(beta 1-->4)Glc beta-OPr and GlcA(beta 1-->3)Gal beta OAll were synthesized
      in a similar way.

PMID- 9784881
TI  - [Suc-Phe-Leu-Phe-SBzl--a new substrate for functional study of Escherichia coli
      ATP-dependent Lon-proteinase and its modified forms].
AB  - A new efficient substrate, Suc-Phe-Leu-Phe-SBzl, was proposed for studying the
      function of the Escherichia coli ATP-dependent Lon protease and its modified
      forms. The kinetic parameters of hydrolysis of the substrate were determined. The
      esterase activity of protease Lon was found to be nucleotide-regulated.

PMID- 9784882
TI  - Depressive thinking and dysfunctional schematic mental models.
AB  - OBJECTIVES: To examine the replicability and generalizability of findings
      suggesting that mood-dependent negative thinking in depression reflects changes
      in the schematic mental models through which the world is interpreted, rather
      than a generalized increase in accessibility of negative constructs. DESIGN:
      Depressed and non-depressed samples were compared on a sentence completion task
      concerning anticipated outcomes of social approval or success. This task was
      designed so that the schematic mental models view predicted more positive
      completions from depressed participants, the construct accessibility view
      predicting the opposite. METHODS: A total of 98 depressed participants (scoring >
      15 on the Center for Epidemiologic Studies Depression Scale; CESD) from a
      depressive self-help organization, and 50 non-depressed controls (CESD < 16)
      completed the CESD, Sentence Completion Task and the Dysfunctional Attitude Scale
      (DAS). RESULTS: Depressed participants made more positive completions in the
      Sentence Completion Task, and scored higher on the DAS than controls. Subanalyses
      suggested that the depressed group's increased positive completions were
      accounted for largely by those currently in psychiatric treatment; these
      participants also showed greater evidence of dysfunctional schematic models on
      DAS. CONCLUSIONS: For depressed participants in psychiatric treatment, results
      replicate previous findings, supporting the view that negative depressive
      thinking reflects a change in schematic mental models through which the world is
      interpreted. Results are inconsistent with predictions from the construct
      accessibility view. The results have methodological implications for the use of
      the sentence completion task in future studies.

PMID- 9784883
TI  - Early attachment experience and recovery from psychosis.
AB  - OBJECTIVES: Two studies were carried out to investigate the relationship between
      coping styles and co-morbid depression in people adjusting to the onset of
      psychosis. Evaluative thinking and early attachment experiences were also
      examined. METHODS AND DESIGN: In Study 1, a 39-item Recovery Style Questionnaire
      (RSQ) was developed to measure recovery style in people with psychosis, based on
      McGlashan, Levy & Carpenter's (1975) interview measure of recovery style. Fifty
      six participants completed both the RSQ and McGlashan's interview-based measure.
      Study 2 explores the relationship between these styles of recovery, depression
      and early childhood attachment experiences. Thirty-six people participated.
      RESULTS: The RSQ was both reliable and correlated highly with McGlashan's
      interview-based measure. We found that the RSQ, in keeping with the interview
      based measure, was bimodally distributed, thus supporting McGlashan's contention
      that they define two distinct recovery styles termed 'integration' and 'sealing
      over'. As predicted, 88 per cent of the 'sealers' were moderately to severely
      depressed compared to 52 per cent of the 'integrators' who were mildly depressed
      with no members of the 'integration' group experiencing moderate to severe
      depression (p < .0003). Patients who employed the sealing over recovery style
      also made significantly more negative self-evaluations than did patients in the
      integration group and also perceived their parents to be significantly less
      caring than those in the integration group. CONCLUSIONS: These findings are
      explained in terms of a multi-axial model incorporating personality structure and
      development as well as mental disorder. It is suggested that those individuals
      with a poorly developed sense of self defend against the threat of psychosis
      using denial. Clinical implications are discussed and more research is suggested
      to further investigate the links between evaluative and inferential thinking in
      co-morbid depression, and how such thinking relates to early childhood
      experience.

PMID- 9784884
TI  - Reasoning biases in delusion-prone individuals.
AB  - OBJECTIVES: The objective was to test whether individuals high in delusional
      ideation exhibit a reasoning bias on tasks involving hypothesis testing and
      probability judgments. On the basis of previous findings (e.g. Garety, Hemsley &
      Wessely, 1991), it was predicted that individuals high in delusional ideation
      would exhibit a 'jump-to-conclusions' style of reasoning and would be less
      sensitive to the effects of random variation, in comparison to individuals low in
      delusional ideation. DESIGN: A non-randomized matched groups design was employed
      enabling the performance of the delusion prone individuals to be compared to that
      of a control group. METHOD: Forty individuals, selected from the normal
      population, were divided into groups high and low in delusional ideation,
      according to their scores on the Peters et al. Delusions Inventory (Peters, Day &
      Garety, 1996), and were compared on two tasks involving probability judgment and
      two tasks involving hypothesis testing. RESULTS: Although no significant
      differences were found on tasks involving hypothesis testing and the aggregation
      of probabilistic information, it was found that individuals high in delusional
      ideation had a 'jump-to-conclusions' style of data gathering and were less
      sensitive to the effects of random variation, in comparison to individuals low in
      delusional ideation. CONCLUSIONS: In conclusion, although individuals high in
      delusional ideation were not found to have a general reasoning bias, some
      evidence of a more specific bias was found. It is thought that these aberrations
      may play some role in delusion formation in schizophrenia and paranoia.

PMID- 9784885
TI  - Parental autobiographical memory: is this a helpful clinical measure in
      behavioural child management?
AB  - OBJECTIVES: The major hypothesis was that specificity scores on the Parent-Child
      Autobiographical Memory Test (PCAMT; Hutchings, 1996) would differentiate between
      mothers of children referred to a child and adolescent mental health service for
      behavioural management, and those who were not referred. Within the referred
      sample, the objective was to examine the relationships between the PCAMT, mental
      health (Beck Depression Inventory; Beck, Ward, Mendelson, Mock & Erbaugh, 1961;
      General Health Questionnaire; Goldberg, 1972) and socio-economic deprivation
      (SED5; Hutchings, 1996) and measures of outcome (Eyberg Child Behavior Inventory;
      Eyberg, 1980). DESIGN: Pre-treatment measures on the PCAMT for the group of
      mothers whose children were referred were compared with measures on the PCAMT
      from a group of mothers of non-referred children of similar ages. Within the
      mothers of the referred sample, correlations of the PCAMT with other measures
      were examined, pre- and post-treatment. METHODS: Pre-treatment PCAMT scores from
      26 mothers of children with behaviour management problems from consecutive
      referrals to a child and adolescent mental health service were compared with
      PCAMT scores from 22 mothers of children of a similar age from a local playgroup.
      Within the referred group, the PCAMT was administered before (N = 26) and after
      (N = 16) treatment. The 16 treated families received behavioural management
      advice. RESULTS: The PCAMT distinguished between parents of children referred for
      behavioural management advice and a non-clinical sample. Within the referred
      group it also distinguished between those who received treatment and those who
      did not attend treatment. CONCLUSIONS: The PCAMT is considered to have the
      potential of being a useful instrument for identifying referred children whose
      mothers may not attend for treatment and possibly for identifying those mothers
      who would benefit most from concentrating on attending and observation skills in
      child management training.

PMID- 9784886
TI  - Reported sexual abuse and subsequent psychopathology among women attending
      psychology clinics: the mediating role of dissociation.
AB  - OBJECTIVE: While there is now a good clinical research base that outlines the
      links between reported sexual abuse and psychological symptoms and disorders,
      there is less of an understanding of the psychological processes mediating that
      relationship. This study assessed the role of dissociation as a mediator between
      reported sexual abuse and a range of psychopathological characteristics. DESIGN:
      A patient-series design was used. METHOD: Participants were an unselected sample
      of 45 women attending clinical psychology services. Each woman was interviewed
      regarding a reported history of sexual abuse, and completed standardized measures
      of general psychopathology, borderline personality disorder characteristics and
      dissociation. RESULTS: Sexual abuse per se was associated with the extent of
      depression, somatization, compulsive behaviour, phobic symptoms and borderline
      personality disorder characteristics. In each case, dissociation served as a
      complete mediator in that link. However, the same mediating relationship was not
      found when attempting to explain the greater psychopathological impact of more
      'severe' forms of abuse (childhood experiences; intra-familial abuse).
      CONCLUSION: These findings suggest that the effective of clinical work with these
      psychopathological features would be enhanced if dissociation symptoms were
      addressed in women with a reported history of sexual abuse. However, the
      importance of that therapeutic target may be unrelated to the severity of the
      psychological disturbance.

PMID- 9784887
TI  - A new performance-curve method for the detection of simulated cognitive
      impairment.
AB  - OBJECTIVE: To evaluate a new performance-curve method for detecting simulated
      cognitive impairment. DESIGN: The method was based on quantitative analysis of
      choice reaction times in a series of eight matching-to-sample tasks of graded
      complexity, in which participants were required to identify which of two
      comparison stimuli was identical to a simultaneously presented sample stimulus.
      The stimuli consisted of arrays of letters, the number of letters ranging from 1
      to 10 in the eight tasks. METHODS: Mean reaction times of a standardization group
      of 20 healthy young adults were used to construct regression equations to
      describe the behaviour of three test groups: 20 healthy individuals instructed to
      perform to the best of their ability (non-simulators), 20 healthy individuals
      instructed to simulate cognitive impairment incurred as a result of a head injury
      (simulators), and 25 patients with a history of closed head injury (patients).
      RESULTS: There was a linear relationship between individual participants'
      latencies and the mean latencies of the standardization sample; the patient group
      showed steeper slopes, and the simulators higher intercepts, than the non
      simulator group. A univariate measure of performance, based on the proportionate
      increase in latency corresponding to a standard increase in the standardization
      group's latency was able to identify 14/20 simulators while misclassifying 2/20
      non-simulators and 2/25 patients. Other measures, including the number of errors
      made in the choice reaction time task and in recognition memory tasks, and a
      performance-curve measure based on Raven's Standard Progressive Matrices, were
      less successful in identifying simulators. CONCLUSIONS: This new performance
      curve method may prove to be a useful addition to tests currently used to
      diagnose simulated cognitive impairment in clinical and medicolegal settings.

PMID- 9784888
TI  - Cognitive dissonance. 1: An overview of the literature and its integration into
      theory and practice in clinical psychology.
AB  - PURPOSE: Clinical psychology may not be making full use of the experimental
      psychological research available to it. The purpose of this article is to review
      the literature on cognitive dissonance in order to assess its usefulness in
      developing and deconstructing clinical psychological therapies and practice.
      METHODS: Experimental, theoretical and review articles were examined in relation
      to their possible clinical implications, and included in this review if they
      related to the arousal, maintenance and reduction of the state termed cognitive
      dissonance. Well replicated findings based on experimentally sound paradigms were
      integrated to produce an overall view of the evidence in favour of the existence
      of these processes, and of the principles behind them. RESULTS: It is concluded
      that there is an effect on attitudes and behaviour of creating inconsistency in
      individuals, and that this is not explained away by alternative theories, which
      in many cases refer to special conditions which maximally arouse dissonance. The
      dissonant state lasts for a few minutes, but its effects can last for up to two
      weeks, and might be reinstated by reintroducing the original inconsistency.
      Individuals can react to dissonance through a variety of cognitive alterations
      which reinstate consistency. The choice of response is a function of its salience
      and the difficulty in its execution. CONCLUSIONS: The literature supports the
      existence of the phenomenon termed cognitive dissonance, and one can distil the
      principles underlying its production, maintenance and reduction. This body of
      literature may provide insights into the conduct of therapy generally, as well as
      into the mechanisms of specific therapies which may guide modifications or
      development of alternative interventions.

PMID- 9784889
TI  - Cognitive dissonance. 2: A theoretical grounding of motivational interviewing.
AB  - PURPOSE: The aim of this article is to demonstrate the utility of the concept of
      cognitive dissonance in clinical psychology by showing how it may underlie an
      existing intervention. The technique of motivational interviewing (MI) is taken
      as an example of an area where the literature on cognitive dissonance can find
      such an application. The further aim of this exercise is to utilize insights from
      cognitive dissonance to suggest possible modifications to the intervention as it
      currently stands. METHODS: A mapping is undertaken of principles of cognitive
      dissonance as found in Draycott & Dabbs (1998) onto the description of nature,
      principles and techniques of MI as set out by Miller & Rollnick (1991). Following
      this, areas where insights from cognitive dissonance are ignored or underutilized
      are drawn out and used to suggest modifications to MI. RESULTS: The nature,
      principles and techniques of MI are, without exception, found to relate to one or
      more of the principles of cognitive dissonance. Criticisms and amendments to the
      technique of MI can be offered with the aim of making this mapping of cognitive
      dissonance more exact. Several practical suggestions can be made and a more
      structured approach offered. CONCLUSIONS: The concept of cognitive dissonance can
      clearly be seen to be of use in understanding the mechanism of action of MI. It
      can further be of use in guiding modifications to this existing intervention.
      This concept, and others available through the experimental psychological
      literature, can be of use in all branches of clinical psychology.

PMID- 9784890
TI  - Post-traumatic stress disorder after subarachnoid haemorrhage.
AB  - OBJECTIVE: Draw attention to the presence of post-traumatic stress disorder in
      aneurysmal subarachnoid haemorrhage patients. DESIGN: Case review of 28 patients
      referred to clinical neuropsychology via a neurosurgery out-patient clinic.
      METHOD: Clinical interview of patients presenting with anxiety related to their
      medical condition. RESULTS: In 50 per cent of patients anxiety was found to be
      the main presenting problem and 32 per cent of referred patients met the
      diagnostic criteria for post-traumatic stress disorder. CONCLUSION: The case
      review identified significant psychological morbidity in patients with good
      physical recovery. This requires detailed scientific evaluation in future studies
      of outcome.

PMID- 9784891
TI  - Selected bacterial diarrheas.

PMID- 9784892
TI  - Antibiotics.
AB  - Antibiotics may be a helpful addition to your therapy for IBD. Although it sounds
      as if there are a number of side effects, most patients do well, without any
      problems. If you develop new or worsening symptoms, or if you have other
      concerns, feel free to discuss them with your physician.

PMID- 9784893
TI  - Viral hepatitis in the transplant recipient.

PMID- 9784894
TI  - Thoughts on the presentation and relevance of scientific results from clinical
      research projects.

PMID- 9784895
TI  - Canadian Association of Gastroenterology Practice Guidelines: management of
      noncardiac chest pain.

PMID- 9784896
TI  - Canadian Association of Gastroenterology Practice Guidelines: evaluation of
      dysphagia.

PMID- 9784898
TI  - Electrogastrography: a noninvasive technique to evaluate gastric electrical
      activity.
AB  - Electrogastrography (EGG) is the recording of gastric electrical activity (GEA)
      from the body surface. The cutaneous signal is low in amplitude and consequently
      must be amplified considerably. The resultant signal is heavily contaminated with
      noise, and visual analysis alone of an EGG signal is inadequate. Consequently,
      EGG recordings require special methodology for acquisition, processing and
      analysis. Essential components of this methodology involve an adequate system of
      digital filtering, amplification and analysis, along with minimization of the
      sources of external noise (random motions of the patient, electrode-skin
      interface impedance, electrode bending, obesity, etc) and a quantitative
      interpretation of the recordings. There is a close relationship between GEA and
      gastric motility. Although it has been demonstrated that EGG satisfactorily
      reflects internal GEA frequency, there is not acceptable correlation with gastric
      contractions or gastric emptying. Many attempts have been made to relate EGG
      'abnormalities' with clinical syndromes and diseases; however, the diagnostic and
      clinical value of EGG is still very much in question.

PMID- 9784897
TI  - Canadian Association of Gastroenterology Practice Guidelines: evaluation of
      abnormal liver enzyme tests.

PMID- 9784899
TI  - Influence of sex, age and smoking status on patient comfort during gastroscopy
      with pharyngeal anesthesia by a new benzocaine-tetracaine preparation.
AB  - Thirty-seven patients underwent gastroscopy under pharyngeal anaesthesia with
      benzocaine-tetracaine (Endospray; Axcan Pharma). Patients recorded their
      perception of intubation, of the rest of the procedure, of taste and of throat
      well-being on visual analogue scales. Throat well-being and taste scores were
      better for men than for women. There was a strong trend for smokers to be more
      intolerant to intubation than nonsmokers. There was a weak but significant
      correlation for younger patients to be more intolerant to intubation. This study
      points to age and smoking status as possible factors influencing the perception
      of gastroscopy under pharyngeal anesthesia.

PMID- 9784900
TI  - From bench to bedside and back--report on the European Helicobacter pylori Study
      Group Xth International Workshop on Gastroduodenal Pathology and Helicobacter
      pylori.
AB  - The Xth International Workshop on Gastroduodenal Pathology and Helicobacter
      pylori was held in Lisbon, Portugal, from September 12 to 14, 1997. State-of-the
      art reviews and research findings were presented to over 2000 participants. This
      review focuses on important new developments and serves as a rapid communication
      of clinically relevant material.

PMID- 9784901
TI  - Personal viewpoint: new developments in the therapy of diabetic hypertensive
      disease. The ABCD study adds to strong evidence favoring the prime use of ACE
      inhibitors. Appropriate Blood Pressure Control in Diabetes.

PMID- 9784903
TI  - Effect of rotational coronary atherectomy on peripheral endothelin-1, atrial
      natriuretic peptide, and cyclic adenosine monophosphate plasma levels.
AB  - We investigated the effects of coronary rotational atherectomy (PTCRA) on plasma
      levels of endothelin-1 (ET-1), atrial natriuretic peptide (ANP), and cyclic
      adenosine monophosphate (cAMP). We studied 14 patients undergoing PTCRA and
      compared them with 14 patients undergoing plain balloon angioplasty. Blood
      samples were taken from the femoral vein at baseline, after the end of the
      atherectomy, after the first balloon inflation, after the end of the procedure,
      and 4 hours later. ET-1 increased in the angioplasty group from 6.3 +/- 3.2
      pmol/L at baseline to 8.5 +/- 3.9 pmol/L at the end of the procedure (F = 3.83, P
      = .02), whereas it did not change in the PTCRA group. ANP increased in the PTCRA
      group from 78.1 +/- 15.7 pmol/L at baseline to 89.7 +/- 24.0 pmol/L at the end of
      the procedure (F = 6.75, P = .0001), whereas it did not change in the angioplasty
      group. cAMP decreased in the PTCRA group, whereas it did not change in the
      angioplasty group. In conclusion, ET-1 increases less, ANP increases more, and
      cAMP decreases more during atherectomy than during plain balloon angioplasty.

PMID- 9784902
TI  - Cardiovascular safety of transdermal nicotine patches in patients with coronary
      artery disease who try to quit smoking.
AB  - Nicotine patches are commonly used by people who try to quit smoking. Because
      high doses of nicotine may increase heart rate and potentiate cardiac arrhythmia
      or ischemia, its use in patients with coronary artery disease was investigated.
      The objective was to assess the cardiovascular safety of nicotine patches in
      patients with coronary artery disease (CAD) who try to quit smoking. The study
      was conducted in a double-blind, placebo-controlled, randomized fashion over a 2
      week period. One hundred and six patients with CAD who wished to stop smoking and
      were taking part in a smoking cessation program were included. Fifty-two patients
      received nicotine patches (Nicotinell) and 54 received placebo patches. The
      cardiovascular effects of nicotine patches were assessed by repeated ambulatory
      ECG monitoring (AEM) and exercise testing. There were no changes in the resting
      heart rate and in the systolic or diastolic blood pressure between the screening
      and the two phases of the study in both the Nicotinell and placebo groups.
      Repeated 48-hour AEM revealed that there were no significant changes in the
      number and duration of ischemic episodes in both groups. There was no change in
      the frequency of atrial or ventricular arrhythmias. Exercise duration and time to
      1-mm ST-segment depression increased in both groups during the double-blind
      treatment phase. More patients in the Nicotinell group claimed tobacco abstinence
      compared with the placebo group (27% vs. 13%). The use of nicotine patches did
      not cause aggravation of myocardial ischemia or arrhythmia in coronary patients
      and therefore can be used as a method to promote smoking cessation in this high
      risk group.

PMID- 9784904
TI  - Effect of probucol on smooth muscle cell proliferation and dedifferentiation
      after vascular injury in rabbits: possible role of PDGF.
AB  - We previously reported a clinical study in which probucol reduced the restenosis
      rate. The mechanism of this effect is unclear. Restenosis is characterized by
      neointimal hyperplasia caused by proliferation of smooth muscle cells (SMCs),
      which increases the expression of Platelet-derived growth factor (PDGF)-A and
      SMemb. SMemb, a non-muscle-type myosin heavy chain most predominantly expressed
      in embryonic smooth muscle, can be used as a good molecular marker for
      dedifferentiated SMC. The aim of this study was to analyze the effect of probucol
      on neointimal proliferation and the level of expression of PDGF-A and SMemb after
      balloon injury in rabbits. Probucol was given orally 1.3 g/d from 2 weeks prior
      to carotid balloon injury to the time of killing (2 or 4 weeks after balloon
      injury). Intimal area was determined histologically using a computerized
      morphometry program. For quantification of SMC proliferation, alpha-actin
      positive cells and proliferating cell nuclear antigen (PCNA)-labeled cells were
      counted. The expression of PDGF-A and SMemb mRNA was analyzed by the RNase
      protection assay. SMemb expression was also examined by immunohistochemistry.
      Probucol remarkably decreased intimal area by 70% and the number of SMC and PCNA
      labeled cells in the intima. The expression of PDGF-A mRNA was significantly
      increased after balloon injury in untreated rabbits, whereas it was markedly
      suppressed with probucol treatment. The expression of SMemb was significantly
      increased in injured arteries at mRNA and protein levels. However, probucol did
      not suppress SMemb expression. Probucol is effective in preventing SMC
      proliferation, which is possibly due to a decrease in the expression of PDGF.

PMID- 9784905
TI  - Beyond coagulation: fibrinogen as a cause of cardiovascular surgical disease.
AB  - Fibrinogen is generally considered to be an important mediator of clot formation.
      However, its effects on clots and perhaps other more direct effects may also make
      it a powerful mediator in the genesis and progression of atheromatous disease.
      Indeed, raised fibrinogen levels may pose as great a cardiovascular risk as
      classical risk factors such as elevated blood pressure or cholesterol levels. The
      plasma fibrinogen level of any given individual, and its associated
      cardiovascular risk, is dependent upon an interaction between environmental and
      intrinsic (genetic) factors. Most environmental factors associated with elevated
      fibrinogen levels are also potent cardiovascular risk factors (e.g., cigarette
      smoking). Less is known of the role played by genetic factors. However, as
      research into the genotypic influences on both basal and "stimulated" fibrinogen
      production continues, high-risk groups may be identified that may benefit from
      therapeutic intervention aimed at lowering plasma fibrinogen.

PMID- 9784906
TI  - Postcardioplegic myocardial recovery: effects of halothane, nifedipine, HOE 694,
      and quinacrine.
AB  - Halothane has been shown to be a powerful myocardial protectant during
      normothermic cardioplegic arrest and subsequent reperfusion. In view of its
      multiple effects on cellular Ca2+ movements and the role of this ion in ischemia
      reperfusion injury, the questions of whether halothane is capable of maximally
      protecting the heart or whether combination therapy of halothane with other Ca2+
      blocking agents may be more effective arose. Therefore, the effects of
      combination therapy with halothane and a calcium antagonist (nifedipine), or a
      Na+/H+ inhibitor (HOE 694), or a Na+/Ca2+ inhibitor (quinacrine) on
      postcardioplegic functional recovery were evaluated. The isolated perfused rat
      heart subjected to 45 minutes normothermic cardiac arrest was used as an
      experimental model. Dose-response curves were performed for each drug. Using the
      optimal dosage for each drug, the following results were obtained: (1) Nifedipine
      (10(-7) M; administered retrogradely 10 minutes before and after cardioplegia)
      and halothane (1.5% administered during cardioplegia), when administered
      separately, improved functional recovery. Combination therapy did not further
      improve protection. (2) HOE 694 (10(-7) M) or quinacrine (10(-9) M) improved post
      cardioplegic functional recovery when added for 2 minutes at the onset of
      reperfusion. Simultaneous administration of HOE 694 and 1.5% halothane was the
      only combination that yielded additive protection. (3) Quinacrine, a
      phospholipase and Na+/Ca2+ exchanger inhibitor, appeared to be the most powerful
      drug used. In summary, the results obtained indicate that interventions aimed at
      preventing intracellular Ca2+ overload improve recovery after cardioplegic
      arrest. The beneficial effects of halothane could be further improved by HOE 694.

PMID- 9784907
TI  - EDRF does not mediate coronary vasodilation secondary to simulated ischemia: a
      study on KATP channels and N omega-nitro-L-arginine on coronary perfusion
      pressure in isolated Langendorff-perfused guinea-pig hearts.
AB  - Several authors have alluded to the possible involvement of EDRF (NO) in ischemia
      induced coronary artery dilation. Alternatively, it has been suggested that
      opening of ATP-dependent K channels could play a key role in this context. We
      studied the effects of sulfonylureas and NG-nitro-L-arginine (LNNA), a specific
      inhibitor of endothelial NO (EDRF) synthesis, on ischemia-induced coronary
      vasodilation in isolated Langendorff-perfused guinea pig hearts arrested with 15
      mM KCl in normal Tyrode, and isolated pig coronary arteries precontracted with 43
      mM KCl. In Isolated Langerdorff-perfused guinea pig heart, when hypoxia was
      simulated by switching 100% O2 in the perfusate to 100% N2, coronary perfusion
      pressure (CPP) fell from 90 cm H2O by 45 +/- 5 cm H2O. In the presence of LNNA, a
      specific inhibitor of NO synthetase in endothelial cells, CPP dropped by 44 +/- 6
      cm H2O (n = 6; +/- SEM, no statistically significant). On biochemical simulation
      of ischemia (addition of iodoacetate [IAA]), CPP dropped 40 +/- 6 cm H2O, and in
      experiments performed under the same conditions but in the presence of LNNA, CPP
      dropped by 38 +/- 5 cm H2O (n = 6; +/- SEM; not statistically significant). When
      ischemia was simulated metabolically by equimolar replacement of 10 mM glucose
      with 2-deoxyglucose (DOG), an inhibitor of glycolysis CPP decreased by 24 +/- 1
      cm H2O (n = 6; +/- SEM) after 15 minutes. This fall in CPP was almost prevented
      by 20 microM glibenclamide, whereas in the presence of 20 microM LNNA the DOG
      induced decrease in CPP was not significantly inhibited, and CPP decreased by 22
      +/- 2.6 cm H2O (n = 6; +/- SEM). In isolated pig coronary artery rings, maximal
      tension, achieved by depolarizing the smooth muscle cells by 43 mM KCl, decreased
      by 37 +/- 7% upon simulated hypoxia by replacing 100% O2 with 100% N2 in the
      perfusate (n = 6; +/- SEM) in arteries with intact endothelium. In arteries
      without endothelium, maximal tension also dropped by 35 +/- 6% (not statistically
      significant). In the same experiments the decrease in tension could be largely
      inhibited in the presence of 50 microM glibenclamide. Our results clearly show
      that in isolated perfused guinea pig hearts, as well as in isolated pig coronary
      arteries, EDRF does not play a decisive role in the coronary dilatory response to
      hypoxia and ischemia.

PMID- 9784908
TI  - Effect of verapamil on heart rate variability after an acute myocardial
      infarction. Danish Verapamil Infarction Trial II.
AB  - Because decreased heart rate variability measured after an acute myocardial
      infarction (AMI) has been demonstrated to predict subsequent mortality and sudden
      death, and an efficacy analysis of the Danish Verapamil Infarction Trial II
      (DAVIT II) demonstrated that long-term postinfarction treatment with verapamil
      significantly reduced sudden death, the aim of the present substudy was to
      evaluate the effect of verapamil on heart-rate variability in the time and
      frequency domain, measured in two 5-minute segments during the day and night.
      Thirty-eight patients were examined by Holter monitoring, at 1 week, that is,
      before randomization, and at 1 month after infarction; 22 of the patients were
      examined 12-16 months after infarction as well. In both treatment groups
      (verapamil and placebo) no significant alteration of heart rate variability
      during the day-time was demonstrated from before to after 1 and 12-16 months of
      treatment. In accord with the known reduction of overall heart rate by verapamil,
      a significant increase of mean NN interval from before to after 1 (P = 0.0004)
      and 12-16 months (P = 0.004) of treatment was seen in the verapamil, but not in
      the placebo, group at night. Parameters generally interpreted as an index of
      parasympathetic modulation, that is, RMSSD, pNN50, and high-frequency power,
      increased significantly at 1 month (P = 0.04, P = 0.03, NS, respectively) and 12
      16 months (P = 0.03, P = 0.04, P < 0.05) after AMI in the verapamil, but not in
      the placebo, group. In conclusion, the present study indicates that verapamil
      shifts the autonomic balance to a vagal preponderance or sympathetic attenuation
      in the postinfarction period.

PMID- 9784909
TI  - Acute and chronic effects of propionyl-L-carnitine on the hemodynamics, exercise
      capacity, and hormones in patients with congestive heart failure.
AB  - Carnitine is an important cofactor in the intermediary metabolism of the heart,
      and carnitine deficiency is associated with congestive heart failure. We
      therefore studied the effects of acute (IV bolus, 30 mg/kg body weight) and
      chronic administration (1.5 mg/d for 1 month) of propionyl-L-carnitine on
      hemodynamics, hormone levels, ventricular function, exercise capacity, and peak
      oxygen consumption in 30 patients with chronic congestive heart failure (NYHA II
      III, mean EF 29.5 +/- 7%) in a phase II, parallel, single-blind, randomized, and
      placebo-controlled study. Acute administration of propionyl-L-carnitine caused a
      significant reduction in pulmonary artery and pulmonary wedge pressures at both
      day 1 (P < 0.001) and day 30 (P < 0.05) of the study but no other hemodynamics
      changes. Hormone levels did not change following acute administration of the
      drug. Chronic administration of propionyl-L-carnitine increased peak oxygen
      consumption by 45% (from 16.0 +/- 3 to 23.5 +/- 2 mL/kg/min, P +/- 0.001),
      exercise time by 21% (from 8.1 +/- 0.5 to 9.8 +/- 0.4 minutes, P < 0.01), and
      peak exercise heart rate by 12% (P < 0.01). These changes were concomitant with a
      reduction of pulmonary artery pressure. In the treated group, there was a slight,
      but significant (P < 0.01), reduction in left ventricular dimensions.
      Hemodynamics and hormones measured after 1 month of oral therapy remained
      unchanged, except for a fall in pulmonary artery pressures, with a nonsignificant
      trend towards a fall in filling pressures and plasma norepinephrine. The chronic
      changes in the propionyl-L-carnitine group were seen at 15 days of treatment, and
      no further changes in these parameters were seen at 1 month. We conclude that
      propionyl-L-carnitine increases exercise capacity and reduces ventricular size in
      patients with congestive heart failure. The drug has no significant effects on
      hemodynamics or neurohormone levels. The use of a single-blind design reduces the
      impact of the positive finding on exercise capacity.

PMID- 9784910
TI  - A cost-minimization of heart failure therapy with bisoprolol in the French
      setting: an analysis from CIBIS trial data. Cardiac Insufficiency Bisoprolol
      Study.
AB  - Beta-blocker-induced benefit in heart failure is under intense evaluation.
      Several large-scale mortality trials are currently being performed, with CIBIS II
      evaluating bisoprolol. The economic impact of beta-blocker therapy in heart
      failure has not been previously determined. The present study is a cost
      effectiveness evaluation of bisoprolol treatment based on CIBIS I data. It
      considers direct costs, that is, the bisoprolol medication cost and the cost of
      hospitalization related to heart failure and its complications. Hospitalization
      costs were calculated from the French system of classification (PMSI), which
      provides costs according to homogeneous groups of patients (GHM). The cost
      difference between bisoprolol and placebo in the entire CIBIS population and the
      trial duration result from an increase in cost caused by bisoprolol treatment (+
      2018 Frs/patient) and a decrease in cost related to reduced hospitalization (6349
      Frs/patient). A total savings per patient of about 4330 Frs was produced by
      bisoprolol. Cost reduction is still more pronounced in patients not having a
      history of myocardial infarction. We conclude that heart failure therapy with
      bisoprolol lowers medical healthcare costs, mainly due to the reduced rate of
      hospital admissions for heart failure.

PMID- 9784911
TI  - Elevation of plasma adenosine levels may attenuate the severity of chronic heart
      failure.
AB  - Adenosine is known to be an endogenous cardioprotective substance. Since we have
      reported that adenosine levels increase in patients with chronic heart failure,
      we tested whether further elevation of the adenosine levels due to dipyridamole
      or dilazep for 6 months modulates the pathophysiology of chronic heart failure.
      In patients with chronic heart failure, either dipyridamole (300 mg/d n = 17) or
      dilazep (300 mg/d n = 5) were administered for 6 months. Twenty-two patients
      (mean +/- SE age 58 +/- 4 years old) attending a specialized chronic heart
      failure (CHF) clinic over 6 months and judged as in New York Heart Association
      (NYHA) function class II or III were examined. The other drugs used for the
      treatment of CHF were not altered during the study. There were 5 patients with
      CHF caused by ischemic heart diseases, and 17 patients with either valvular heart
      diseases or dilated cardiomyopathy. We found that increases in the plasma
      adenosine levels (202 +/- 34 and 372 +/- 74) nmol/L before and after dipyridamole
      administration, P < 0.005 ameliorate the severity of CHF (NYHA: 2.1 +/- 0.5 to
      1.7 +/- 0.2). Both ejection fraction and maximal oxygen consumption increased.
      These improvements in the severity of chronic heart failure returned to baseline
      levels 6 months after discontinuation of dipyridamole. Comparable results were
      obtained in the dilazep protocol. We suggest that the elevation of plasma
      adenosine levels improves the pathophysiology of CHF.

PMID- 9784912
TI  - Benzocaine-induced methemoglobinemia--two case reports related to transesophageal
      echocardiography premedication.
AB  - Benzocaine-induced methemoglobinemia is a potentially life-threatening
      complication. We report two cases of methemoglobinemia due to topical benzocaine
      spray used as premedication for transesophageal echocardiography. A high index of
      suspicion is needed for this readily treatable condition.

PMID- 9784913
TI  - Human respiratory muscles: sensations, reflexes and fatiguability.
AB  - 1. Given the importance of the ventilatory 'pump' muscles, it would not be
      surprising if they were endowed with both sensory and motor specializations. The
      present review focuses on some unexpected properties of the respiratory muscle
      system in human subjects. 2. Although changes in blood gas tension were long held
      not to influence sensation directly, studies in subjects who are completely
      paralysed show that increases in arterial CO2 levels elicit strong sensations of
      respiratory discomfort. 3. Stretch reflexes in human limb muscles contain a
      monosynaptic spinal excitation and a long-latency excitation. However,
      inspiratory muscles show an initial inhibition when tested with brief airway
      occlusions during inspiration. This inhibition does not depend critically on
      input from pulmonary or upper airway receptors. 4. Human inspiratory muscles
      (including the diaphragm) have been considered to fatigue during inspiratory
      resistive loading. However, recent studies using phrenic nerve stimulation to
      test the force produced by the diaphragm show that carbon dioxide retention
      (hypoventilation) and voluntary cessation of loading occur before the muscles
      become overtly fatigued.

PMID- 9784915
TI  - Role of hepatic fatty acid:coenzyme A ligases in the metabolism of xenobiotic
      carboxylic acids.
AB  - 1. Formation of acyl-coenzymes (Co)A occurs as an obligatory step in the
      metabolism of a variety of endogenous substrates, including fatty acids. The
      reaction is catalysed by ATP-dependent acid:CoA ligases (EC 6.2.1.1-2.1.3; AMP
      forming), classified on the basis of their ability to conjugate saturated fatty
      acids of differing chain lengths, short (C2-C4), medium (C4-C12) and long (C10
      C22). The enzymes are located in various cell compartments (cytosol, smooth
      endoplasmic reticulum, mitochondria and peroxisomes) and exhibit wide tissue
      distribution, with highest activity associated with liver and adipose tissue. 2.
      Formation of acyl-CoA is not unique to endogenous substrates, but also occurs as
      an obligatory step in the metabolism of some xenobiotic carboxylic acids. The
      mitochondrial medium-chain CoA ligase is principally associated with metabolism
      via amino acid conjugation and activates substrates such as benzoic and salicylic
      acids. Although amino acid conjugation was previously considered an a priori
      route of metabolism for xenobiotic-CoA, it is now recognized that these highly
      reactive and potentially toxic intermediates function as alternative substrates
      in pathways of intermediary metabolism, particularly those associated with lipid
      biosyntheses. 3. In addition to a role in fatty acid metabolism, the hepatic
      microsomal and peroxisomal long-chain-CoA-ligases have been implicated in the
      formation of the acyl-CoA thioesters of a variety of hypolipidaemic and
      peroxisome proliferating agents (e.g. clofibric acid) and of the R(-)-enantiomers
      of the commonly used 2-arylpropionic acid non-steroidal anti-inflammatory drugs
      (e.g. ibuprofen). In vitro kinetic studies using rat hepatic microsomes and
      peroxisomes have alluded to the possibility of xenobiotic-CoA ligase
      multiplicity. Although cDNA encoding a long-chain ligase have been isolated from
      rat and human liver, there is currently no molecular evidence of multiple
      isoforms. The gene has been localized to chromosome 4 and homology searches have
      revealed a significant similarity with enzymes of the luciferase family. 4.
      Increasing recognition that formation of a CoA conjugate increases chemical
      reactivity of xenobiotic carboxylic acids has led to an awareness that the
      relative activity, substrate specificity and intracellular location of the
      xenobiotic-CoA ligases may explain differences in toxicity. 5. Continued
      characterization of the human xenobiotic-CoA ligases in terms of
      substrate/inhibitor profiles and regulation, will allow a greater understanding
      of the role of these enzymes in the metabolism of carboxylic acids.

PMID- 9784914
TI  - Sex steroid control of mood, mental state and memory.
AB  - 1. Sex steroid hormones exert profound effects on mood and mental state. Thus, in
      women, oestrogen is thought to protect against depression and delay the onset of
      schizophrenia and Alzheimer's disease. 2. Our studies in the female rat show that
      oestradiol, in its positive feedback mode for gonadotrophin release, increases
      the expression of genes for the 5-hydroxytryptamine 5-HT2A receptor and the
      serotonin transporter (SERT) in the dorsal raphe nucleus and the density of 5
      HT2A receptor and SERT sites in regions of the forebrain that, in the human, are
      concerned with cognition, mental state, emotion and memory. 3. In the male rat,
      castration decreases while oestrogen and testosterone, but not 5 alpha
      dihydrotestosterone (5 alpha-DHT), increase the density of 5-HT2A receptors in
      forebrain. The fact that 5 alpha-DHT has no effect suggests that the action of
      testosterone depends on its conversion to oestradiol by aromatase. 4. In intact
      rats, the density of 5-HT2A receptors in cerebral cortex is significantly higher
      in pro-oestrous female than in male and dioestrous female rats, showing that the
      spontaneous, preovulatory surge of oestradiol that reaches a peak at 12.00 h of
      pro-oestrus also increases the density of 5-HT2A receptors in cortex. 5.
      Oestrogen and testosterone (by way of its conversion to oestrogen) also stimulate
      the expression of the arginine vasopressin gene in the bed nucleus of the stria
      terminalis of the rodent, a mechanism that plays a key role in olfactory memory.
      6. These actions of sex steroid hormones are discussed in the context of genomic
      versus non-genomic mechanisms, the recent discovery that there are two oestradiol
      receptors with different distributions in brain, the significance of our findings
      for our understanding of the control of mood, mental state and memory and the
      mechanism by which oestrogen stimulation of the 5-HT2A receptor could delay the
      onset of Alzheimer's disease.

PMID- 9784916
TI  - Cytochrome P450 knockout mice: new toxicological models.
AB  - 1. Despite the frenetic pace of cytochrome P450 (CYP) research, important
      questions remain about the possible role of xenobiotic-metabolizing CYP in
      development and cellular homeostasis. 2. The recent experimental development of
      CYP null mouse lines has provided valuable new models for addressing these
      issues, as well as providing novel in vivo models to study the precise role of
      CYP in chemical-mediated toxicity. 3. The present review summarizes results from
      the three Cyp gene knockout mouse lines generated so far and looks at likely
      future directions of this research field. 4. Also discussed are null mouse lines
      with targeted mutations in genes encoding receptors having primary roles in Cyp
      gene regulation.

PMID- 9784917
TI  - Increased levels of endothelin ETB receptor mRNA in human omental arteries after
      organ culture: quantification by competitive reverse transcription-polymerase
      chain reaction.
AB  - 1. Using competitive reverse transcription-polymerase chain reaction (RT-PCR) and
      in vitro pharmacology, smooth muscle endothelin ETB receptor expression was
      studied in segments of human omental artery, fresh and after organ culture for 1
      and 5 days. 2. The competitive RT-PCR assay used in the present study uses an
      internal RNA standard bearing a 69 b.p. deletion in order to control all steps of
      the reaction, including the RT step. Control experiments showed linearity over
      five subsequent 1:10 dilutions and a wide range of cycle numbers. The assay was
      able to quantify subattomolar concentrations in samples under 1 microgram total
      RNA, making it possible to measure mRNA expression even in small tissue biopsies.
      3. In fresh arteries, ETB mRNA levels were 0.19 +/- 0.05 amol/microgram total RNA
      (range 0.03-0.42 amol/microgram; n = 8). After organ culture, an increase in ETB
      mRNA levels by 317 +/- 28 and 288 +/- 12% was found at days 1 and 5, compared
      with fresh arteries, respectively. 4. In vitro pharmacology showed that
      endothelin (ET)-1 induced a strong and potent contraction in fresh arteries,
      whereas the selective ETB receptor agonist IRL 1620 failed to induce a
      significant contraction. The ET-1-induced contraction was not altered in potency
      or Emax after organ culture for 1 and 5 days. In contrast, IRL 1620 induced a
      clear contraction after 1 day, which increased further in both Emax and potency
      after 5 days organ culture. 5. Our results indicate that a massive new
      transcription of ETB receptor mRNA is induced by organ culture, resulting in
      functional contractile ETB receptors on the smooth muscle layer.

PMID- 9784918
TI  - Acute lithium administration impairs the action of parathyroid hormone on rat
      renal calcium, magnesium and phosphate transport.
AB  - 1. Chronic lithium (Li+) treatment commonly produces a state of
      hyperparathyroidism in humans and rat although the mechanism is unknown. 2. The
      present study evaluated the acute effect of Li+ on renal electrolyte transport,
      particularly Ca2+ and Mg2+ in thyroparathyroidectomized (TPTX) and intact rats.
      3. The acute administration of Li+ significantly increased water, sodium,
      potassium and phosphate excretion in both TPTX and intact animals; however, Ca2+
      and Mg2+ excretion was only increased in the intact group. Fractional excretion
      (FE) of Ca2+ and Mg2+ increased from 2.2 +/- 0.2 to 3.5 +/- 0.3% and 12 +/- 2 to
      18 +/- 2%, respectively (P < 0.01). 4. In further experiments in TPTX rats, Li+
      administration inhibited the usual reduction in urine Ca2+ and Mg2+ excretion
      following parathyroid hormone (PTH) administration and inhibited the
      phosphaturia. However, supramaximal concentrations of PTH overcame this
      inhibitory effect. For example, an FECa of 3.8 +/- 0.2% was reduced to 1.4 +/-
      0.2% and 1.7 +/- 0.2% with maximal and supramaximal PTH concentrations,
      respectively, while in the presence of Li+ an FECa of 4.0 +/- 0.2 was decreased
      to 2.8 +/- 0.2 and then 1.9 +/- 0.3% with the same PTH concentrations. 5. The
      inhibitory effect of Li+ was reduced with a lower plasma Li+ concentration (0.7
      +/- 0.2 vs 1.6-1.8 mmol/L). The FEMg results were comparable. 6. These results
      demonstrate that Li+ directly inhibits PTH-mediated renal reabsorption of Ca2+
      and Mg2+ and also blunts PTH-mediated phosphaturia. Therefore, the
      hyperparathyroidism in humans following Li+ treatment may be a consequence of
      reduced renal Ca2+ reabsorption.

PMID- 9784919
TI  - Is a hypertensinogenic factor present in the kidney of hypertensive dahl rats?
AB  - 1. Early studies suggest that hypertension in Dahl salt-sensitive (S) rats is
      related to an uncommon humoral factor that may be released from the kidney. 2. To
      investigate whether the kidney releases a hypertensinogenic factor for developing
      salt-induced hypertension in S rats, we examined a pressor effect, or vascular
      contractive activity of a kidney extract from S rats using a conscious recipient
      rat or an isolated aortic ring. 3. Donor S and Dahl salt-resistant (R) rats were
      fed a 0.4 or 8% NaCl diet for 4 weeks and were then used to provide four kinds of
      kidney extracts (S-0.4%, S-8%, R-0.4%, R-8%). The systolic arterial pressure
      (SAP) was significantly increased in donor S rats fed an 8% NaCl diet compared
      with other donor rat groups. 4. All four types of kidney extract increased mean
      arterial pressure (MAP) in a recipient rat fed a 0.4% NaCl diet. However, the
      increase in MAP observed following infusion of the S-8% extract was the least of
      all groups. An angiotensin AT1 receptor antagonist, CV-11974, abolished any
      pressor effect of all kidney extracts. In an in vitro experiment, all four types
      of kidney extract evoked contractile responses in aortic rings, but elicited no
      significant difference in aortic ring contractile force. 5. These results suggest
      that the kidney of S rats may not release an active hypertensinogenic factor that
      would cause salt-induced hypertension.

PMID- 9784920
TI  - Effects of prostaglandin E2 on renal function and lung liquid dynamics in foetal
      sheep.
AB  - 1. The aim of the present study was to determine the effects of prolonged
      prostaglandin E2 (PGE2) administration on the function of the foetal kidneys and
      lungs in order to gain a greater understanding of the role played by PGE2 in the
      control of foetal fluid balance. By studying the effects of PGE2 at two
      gestational ages, we have also been able to examine the influence of age. 2. We
      studied the effects of 26 h PGE2 infusion on foetal sheep at a mean (+/- SEM) of
      120.0 +/- 0.6 (n = 6) and 139.0 +/- 0.8 (n = 4) days of gestation. In both
      groups, foetal urine production was significantly inhibited throughout the
      infusion period (P < 0.05). In younger, but not older foetuses, urine production
      returned to control values within 24 h of ending the infusion (P < 0.05). This
      PGE2-induced anti-diuresis was associated with foetal hypoxaemia and acidaemia, a
      reduction in free water clearance and an increase in foetal plasma arginine
      vasopressin concentrations (P < 0.05). 3. During PGE2 infusions, foetal breathing
      movements were inhibited, the effect being greater and more sustained in older
      foetuses (P < 0.05). 4. Infusions of PGE2 led to increased lung liquid production
      at both ages (P < 0.05); lung liquid volumes were reduced in older foetuses (P <
      0.05), but were unchanged in younger foetuses. The reduction in lung liquid
      volume in older foetuses may have been due to inhibition of foetal breathing. 5.
      We conclude that increased circulating levels of PGE2 have profound effects on
      foetal renal and lung function which, if sustained, could compromise foetal lung
      development and perinatal well-being.

PMID- 9784921
TI  - Magnolol decreases body temperature by reducing 5-hydroxytryptamine release in
      the rat hypothalamus.
AB  - 1. The effects of magnolol, isolated and purified from the cortex of Magnolia
      officinalis Rehd. et Wils, on thermoregulation and hypothalamic release of 5
      hydroxytryptamine (5-HT) by in vivo microdialysis were assessed in normothermic
      rats and in febrile rats treated with interleukin-1 beta. 2. Intraperitoneal
      administration of magnolol (25-100 mg/kg) produced a decrease in colon
      temperature, an increase in foot skin temperature, a decrease in metabolic rate
      and a decrease in the endogenous release of 5-HT in the rat hypothalamus. 3.
      Depletion of rat brain 5-HT, produced by intracerebroventricular pretreatment
      with 5,7-dihydroxytryptamine, attenuated the magnolol-induced hypothermia,
      cutaneous vasodilation and decreased metabolism. 4. Intracerebroventricular
      administration of (+/-)-2,5-dimethoxy-4-iodoamphetamine (a 5-HT2 receptor
      agonist; 5-10 micrograms/5 microL) increased basal colon temperature and reversed
      the magnolol-induced hypothermia. 5. The increases in both colon temperature and
      hypothalamic 5-HT release produced by interleukin-1 beta injection were
      attenuated by treatment with magnolol. 6. The data suggest that magnolol
      decreases body temperature (due to increased heat loss and decreased heat
      production) by reducing 5-HT release in rat hypothalamus.

PMID- 9784922
TI  - Mechanisms underlying the decrease in circulating angiotensin II concentration
      after sodium loading.
AB  - 1. Acute sodium loading causes a rapid decrease in the circulating concentration
      of angiotensin II (AngII), which is apparent from 5 min after sodium
      administration. This could result from an increase in AngII catabolism and/or a
      decrease in AngII synthesis/secretion. However, the major determinant of AngII
      synthesis is thought to be a change in plasma renin activity, which occurs over a
      longer time frame (15 min). 2. To investigate the mechanisms underlying the rapid
      decrease in plasma AngII engendered by sodium administration, we performed
      metabolic clearance studies in male New Zealand white rabbits before and after a
      hypertonic sodium load of 1.5 mmol/kg as 0.513 mol/L saline i.v. bolus. 3. The
      metabolic clearance rate of AngII increased significantly from 42.2 +/- 9.0
      mL/min per kg before sodium to 110.8 +/- 33.7 mL/min per kg after sodium
      administration (P < 0.05). The calculated or theoretical secretion rate decreased
      from 1470.7 +/- 404.2 to 573.5 +/- 139.5 fmol/min per kg (P < 0.025) in response
      to sodium. 4. We conclude that an increase in AngII metabolism and a decrease in
      synthesis/secretion contribute to the reduction in circulating AngII, which
      occurs in the first 60-90 min after sodium loading.

PMID- 9784923
TI  - Characterization of a major slow oscillation in the mesenteric circulation of
      conscious rats.
AB  - 1. Little is known about spontaneous slow rhythms in regional circulations. The
      present study was aimed at characterizing low-frequency (LF; 78-269 mHz)
      oscillations in the mesenteric and hindquarter circulations of conscious rats. 2.
      Mean arterial pressure (MAP) and indices (pulsed Doppler technique) of mesenteric
      (n = 25) and hindquarter (n = 23) blood flows were recorded in conscious, freely
      moving rats during 1 h periods. Fast Fourier transform analysis was applied to
      beat-to-beat data after resampling at 10 Hz of consecutive 205 s time series. 3.
      A major oscillation centred at 164 +/- 4 mHz was present in the mesenteric, but
      not in hindquarter, circulation. Consequently, LF power accounted for
      approximately 43% of the overall variability of mesenteric blood flow. Cross
      spectral analysis performed between MAP and mesenteric blood flow indicated that
      fractional changes in flow were approximately two-fold of those in MAP, in
      pressure, at the peak frequency. 4. Acute blockade of the autonomic, renin
      angiotensin and vasopressin systems combined with noradrenaline infusion (n = 7)
      reduced the frequency of the mesenteric blood flow oscillation (115 +/- 6 mHz)
      but did not change its contribution to overall flow variability (approximately
      48%). A clear oscillation was still present after acute inhibition of nitric
      oxide (NO) synthesis with NG-nitro-L-arginine methyl ester (n = 8), but was
      virtually absent in chronically guanethidine-sympathectomized rats (n = 12). 5.
      In conclusion, the mesenteric blood flow of conscious rats exhibits a major slow
      oscillation that originates in the mesenteric vasculature and is not secondary to
      the activity of the major pressor systems or to the cyclic release of NO. Because
      of the strong attenuation of the oscillation in sympathectomized rats, we suggest
      that adrenergic vasoconstrictor tone plays a permissive role in its genesis.

PMID- 9784924
TI  - Origin and function of epoxyeicosatrienoic acids in vascular endothelial cells:
      more than just endothelium-derived hyperpolarizing factor?
AB  - 1. In addition to their contribution to endothelium-derived hyperpolarization,
      our understanding of the physiological function of epoxyeicosatrienoic acids
      (EET) within the vascular wall and the actual enzymes involved in the formation
      of the EET in endothelial cells is very limited. In the present study, the
      expression of potential cytochrome P450 (CYP) mono/epoxygenases was assessed in
      endothelial cells isolated from porcine and bovine aortas as well as in the human
      umbilical vein-derived cell lines EA.hy926 and ECV304. 2. Expression of CYP2B1,
      CYP2E1 and CYP3A could be found. The latter were inducible by
      dexamethasone/clofibrate for 72 h, a procedure that also enhanced CYP epoxygenase
      activity in endothelial cells. 3. Enzyme induction yielded increases in
      capacitative Ca2+ entry and membrane hyperpolarization in response to autacoids,
      such as bradykinin and thapsigargin. Thiopentone sodium, an inhibitor of
      endothelial CYP mono/epoxygenase(s), diminished autacoid-induced capacitative
      Ca2+ entry and membrane hyperpolarization, while the effect of EET remained
      unchanged. 4. Epoxyeicosatrienoic acids activated endothelial tyrosine kinase
      activity in a concentration-dependent manner. Arachidonic acid, at 20-fold higher
      concentrations, also increased tyrosine kinase activity. Because only the effect
      of arachidonic acid was inhibited by thiopentone sodium, an inhibitor of CYP
      mono/epoxygenases, these data suggest that arachidonic acid needs to be converted
      to the EET in order to stimulate tyrosine kinase. 5. All these data provide clear
      evidence that the CYP epoxygenase-derived arachidonic acid metabolites (EET) not
      only serve as potential endothelium-derived hyperpolarizing factors but also
      constitute highly active intracellular messengers with a physiological role
      including the control of Ca2+ signalling, membrane potential and tyrosine kinase
      activity.

PMID- 9784925
TI  - Effect and mechanism of cardioplegic arrest on the coronary endothelium-smooth
      muscle interaction.
AB  - 1. During cardiac surgery, the heart is arrested and protected by hyperkalaemic
      cardioplegia. The coronary endothelium may be damaged by ischaemia-reperfusion
      and cardioplegia. Subsequently, this may affect cardiac function immediately
      after cardiac surgery and cause mortality and morbidity. 2. We investigated
      coronary endothelium-smooth muscle interaction after exposure to depolarizing
      (hyperkalaemic; K+ 20 or 50 mmol/L) and hyperpolarizing (the K+ channel opener
      aprikalim) cardioplegia and organ preservation solution (University of Wisconsin
      (UW) solution). Endothelium-dependent relaxation and hyperpolarization of the
      coronary smooth muscle were studied in the porcine and human large conductance
      and micro-coronary arteries. Intracellular free calcium concentration in
      endothelial cells was also measured. 3. The endothelium-derived hyperpolarizing
      factor (EDHF)-mediated relaxation to A23187, bradykinin, and substance P in
      arteries contracted by either U46619 (10 nmol/L) or K+ (25 mmol/L) was reduced
      after exposure to either high K+ or UW solution, but was maximally preserved
      after exposure to aprikalim. The hyperpolarization of the membrane potential in
      response to the above endothelium-derived relaxing factor stimuli was also
      reduced by exposure to depolarizing cardioplegia. Studies in microcoronary
      arteries are in accordance with findings in large arteries. The intracellular
      free calcium concentration remained unchanged after exposure to hyperkalaemia. 4.
      We concluded that: (i) during cardiac surgery, the function of coronary
      circulation may be changed due to exposure to depolarizing cardioplegia or
      preservation solutions; (ii) the functional change in the coronary circulation is
      related to the altered interaction between the endothelium and smooth muscle;
      (iii) depolarizing (hyperkalaemia) cardioplegia or hyperkalaemic organ
      preservation solutions affect endothelium-smooth muscle interaction through the
      EDHF pathway; (iv) EDHF relaxes the porcine large and microcoronary arteries
      through multiple K+ channels; and (v) that hyperpolarizing vasodilators (K+
      channel openers) may protect EDHF-mediated endothelial function when used as
      cardioplegia.

PMID- 9784926
TI  - Endothelium-smooth muscle interaction in cardiac transplantation.
AB  - 1. The inducible isoform of nitric oxide synthase (iNOS) is expressed in human
      and experimental cardiac allografts and is localized to infiltrating macrophages,
      cardiac myocytes, endothelial cells and smooth muscle cells. A recent clinical
      report proposes a causal link between myocardial expression of iNOS and
      ventricular contractile dysfunction, a potentially graft- and life-threatening
      post-transplant complication. 2. Coronary blood flow is elevated in human graft
      recipients with biopsy proven cellular rejection, indicating that vasodilation
      accompanies graft rejection. In Lewis-to-F-344 coronary resistance vessels, which
      show intimal expression of iNOS, pressure-induced myogenic tone is significantly
      inhibited. Selective iNOS inhibition partially reverses the inhibition of
      myogenic tone, confirming that iNOS produces vasoactive nitric oxide (NO) and may
      mediate the rejection-induced vasodilation seen clinically. 3. Endothelial
      dysfunction, identified as loss of endothelium-dependent dilation, has tremendous
      prognostic significance in vascular diseases of multiple aetiologies. In
      transplantation, endothelial dysfunction predicts early cardiac allograft
      vasculopathy and poor clinical outcome. Lewis-to-F-344 coronary vessels develop
      endothelial dysfunction at 1 week post-transplantation, but this is preceded by a
      transient state of endothelial cell hyperfunction, with enhanced endothelial
      production of NO. 4. The normal interaction between endothelial and smooth muscle
      cells in coronary resistance vessels is critical for the regulation of coronary
      blood flow and the maintenance of fluid homeostasis. With allospecific expression
      of iNOS, the inhibition of vascular tone predicts greatly enhanced intravascular
      pressure in precapillary arterioles and capillaries; this would be expected to
      cause a net movement of fluid from the intravascular compartment into the
      myocardial interstitium, resulting in ventricular oedema, non-compliance and poor
      contractile performance.

PMID- 9784927
TI  - Pacemaking in the heart: the interplay of ionic currents.
AB  - 1. There is still a degree of controversy about which currents drive pacemaking
      in the sinoatrial node or sinus venous. Early attempts to identify a single
      'pacemaker current' in these tissues, based on voltage-clamp data, were largely
      unsuccessful, prompting the search for other mechanisms that may contribute to
      rhythmic activity. 2. Whole-cell patch-clamp recording from single cells isolated
      from the sinus venosus of the toad has shown that a voltage-dependent sodium
      current may play a role in pacemaking. This current has a transient component
      that contributes to the action potential upstroke and an inactivation-resistant
      component that contributes to the diastolic depolarization. The relative
      importance of this current in pacemaking is still controversial. 3. The
      development of computer models of pacemaking has contributed greatly to our
      understanding of how ionic currents can interact to produce rhythmic activity.
      Results are presented from one such model, 'Oxsoft Heart', to illustrate the
      different contributions of Ir and INa and to highlight the concept that
      pacemaking is driven by the integrated activity of many processes, rather than by
      any one current in particular. 4. Present models of pacemaking fail to accurately
      reproduce biological observations for certain situations. It is becoming clear
      that many processes contribute to pacemaking and have yet to be fully
      incorporated into models. Recent results regarding the role of intracellular
      calcium buffering and release and their implications, are discussed in this
      context. 5. The control of pacemaking by neurotransmitters is discussed. The
      limitations of single cell models in reproducing many of the complex responses to
      nerve stimulation of multicellular tissue, such as postinhibitory rebound, are
      discussed and possible improvements to models are suggested.

PMID- 9784928
TI  - Driving respiration: the respiratory central pattern generator.
AB  - 1. The central pattern generator (CPG) for respiration is located in the
      brainstem and produces rhythmic synaptic drive for motoneurons controlling
      respiratory muscles. Based on respiratory nerve discharge, the respiratory cycle
      can be divided into three phases: inspiration, postinspiration and stage 2
      expiration. 2. Six basic types of respiratory neuron participate in respiratory
      rhythmogenesis. Their firing and membrane potential patterns are locked to
      different phases of the respiratory cycle. 3. In adult mammals, respiratory
      neurons are subject to excitatory and inhibitory synaptic inputs and show
      extensive synaptic interconnections that are mainly inhibitory. There are
      differences in the relative importance of excitatory and inhibitory synaptic
      drives and the neurotransmitters involved in respiratory rhythmogenesis in
      neonates compared with adults. 4. Respiratory neurons possess a number of
      intrinsic membrane currents that may be involved in central pattern generation,
      including low- and high-voltage-activated calcium, potassium, calcium-dependent
      potassium, sodium and mixed cationic currents. More quantitative information is
      needed about the distribution and characteristics of these ionic currents if we
      are to understand rhythmogenesis. 5. The two main theories for the origin of
      respiratory rhythm are those of pacemaker neuron-driven and synaptic network
      driven CPG. Evidence derived from in vivo and in vitro experiments exists to
      support both of these theories. There may be a significant switch in the
      underlying mechanism driving the respiratory CPG during postnatal development.

PMID- 9784929
TI  - Second-, minute- and hour-metronomes of intestinal pacemakers.
AB  - 1. Movements of the gastrointestinal tract are required for the digestion of food
      and the expulsion of waste products. 2. The present paper will discuss the nature
      of electrical rhythms underlying some intestinal motility patterns. 3. The
      rhythms are generated by pacemakers with cycle rates appropriate to controlling
      individual contractions, motor patternings or switching between different motor
      programmes. 4. Electrical rhythms are discussed with periods of the order of
      seconds, minutes and hours. 5. Particular discussion is centred on rhythms
      recorded from the small and large intestine of the mouse.

PMID- 9784930
TI  - Generation and entrainment of circadian rhythms.
AB  - 1. The present brief review examines some of the new developments in the area of
      circadian rhythm research. 2. The discovery of the mouse clock and m-per genes
      and their similarity to other clock genes like per and tim has provided new
      insight into the control of rhythms in vertebrates. In mice, these genes are
      expressed in the site of the biological clock, the suprachiasmatic nucleus (SCN),
      and so will now become a focus of research into the generation of rhythmicity. 3.
      Because SCN cells expressing endogenous rhythms have a periodicity different from
      24 h, there must be mechanisms in place to reset the rhythms on a daily basis.
      This is achieved in mammals by retinal light perception and neural transmission
      through several discrete pathways to the SCN. 4. The nature of the
      neurotransmitters involved in this transfer of environmental information to the
      timing system is controversial and may even very between similar species but, in
      the rat, there is compelling evidence that a serotonergic pathway is pre-eminent
      in mediating the effects of light. How the re-setting is achieved at the cellular
      level is not known.

PMID- 9784931
TI  - Clinical significance of pharmacokinetic drug interactions with over-the-counter
      (OTC) drugs.

PMID- 9784932
TI  - Sustained relief of chronic pain. Pharmacokinetics of sustained release morphine.
AB  - There are a number of modified release formulations of morphine with recommended
      dosage intervals of either 12 or 24 hours, including tablets (MS Contin, Oramorph
      SR), capsules (Kapanol, Skenan), suspension and suppositories. Orally
      administered solid dosage forms are most popular but significant differences
      exist in the resultant pharmacokinetics and bioequivalence status of morphine
      after both single doses and at steady state. Following single doses, the plasma
      morphine concentrations showed pronounced differences in the 0- to 12-hour period
      with a 4- to 5-fold difference in the mean peak concentration (Cmax) for morphine
      and the time to Cmax (tmax) The area under the concentration-time curve (AUC)
      from 0 to 24 hours for the 4 formulations show greater similarity. None of the
      formulations were shown to be bioequivalent according to US Food and Drug
      Administration (FDA) criteria. At steady state, fluctuations in plasma morphine
      concentrations throughout a 12-hour dosage interval were greatest for MS Contin
      and least for Kapanol. In fact, the relatively small fluctuations in plasma
      morphine concentrations following Kapanol administration suggested the same
      formulation could successfully be used with a 24-hour dosage interval. The
      pharmacokinetic parameters of morphine following Kapanol once daily were similar
      to MS Contin (12 hours) with the obvious exception of the longer tmax. There is
      also another once daily oral morphine preparation (MXL) which has been shown to
      be bioequivalent to Kapanol under fasting conditions only in a single dose study
      in volunteers. Food has been shown to have an effect on the pharmacokinetics of
      morphine following doses of immediate release solution and the modified release
      preparations. However, bioequivalence is generally maintained between the fed and
      fasting states for most preparations. MS Contin tablets have been administered
      rectally, but morphine pharmacokinetic parameters show greater variability
      compared with oral administration and the 2 routes are not bioequivalent. The
      results suggest a slower rate but greater extent of morphine adsorption. Somewhat
      similar results were obtained when Kapanol granules are administered rectally.
      The morphine pharmacokinetics following administration of a specifically
      formulated controlled release suppository showed less variability (rectal
      bioavailability was 42%). The pronounced differences in morphine pharmacokinetics
      between the various formulations are not translated into measurable differences
      in the pharmacodynamic effects of pain relief and adverse effects. The lack of
      bioequivalence between some of the formulations suggests that care should be
      exercised if physicians change modified release formulations as dosage
      adjustments may be necessary in some patients.

PMID- 9784933
TI  - Clinical pharmacokinetics of nisoldipine coat-core.
AB  - Nisoldipine, a calcium antagonist of the dihydropyridine type, is the active
      ingredient of the controlled release nisoldipine coat-core (CC) formulation. In
      humans, the absorption from nisoldipine CC occurs across the entire
      gastrointestinal tract with an increase in bioavailability in the colon because
      of the lower concentrations of metabolising enzymes in the distal gut wall.
      Although nisoldipine is almost completely absorbed, its absolute bioavailability
      from the CC tablet is only 5.5%, as a result of significant first-pass metabolism
      in the gut and liver. Nisoldipine is a high-clearance drug with substantial
      interindividual and relatively lower intraindividual variability in
      pharmacokinetics, dependent on liver blood flow. Nisoldipine is highly (> 99%)
      protein bound. Its elimination is almost exclusively via the metabolic route and
      renal excretion of metabolites dominates over excretion in the faeces. Although
      nisoldipine is administered as a racemic mixture, its plasma concentrations are
      almost entirely caused by the eutomer as a result of highly stereoselective
      intrinsic clearance. Nisoldipine CC demonstrates linear pharmacokinetics in the
      therapeutic dose range and its steady-state pharmacokinetics are predictable from
      single dose data. Steady-state is reached with the second dose when the drug is
      given once daily and the peak-trough fluctuations in plasma concentration is
      minimal. Plasma-concentrations of nisoldipine increase with age. Careful dose
      titration according to individual clinical response is recommended in the
      elderly. Nisoldipine CC should not be used in patients with liver cirrhosis,
      though dosage adjustments in patients with renal impairment are not necessary.
      Inter-ethnic differences in its pharmacokinetics are not evident. Owing to
      inhibition of metabolising enzymes, a small dosage adjustment decrement for
      nisoldipine CC may be required when it is given in combination with cimetidine.
      Concomitant ingestion of nisoldipine with grapefruit juice should be avoided.
      Inducers of cytochrome P450 (CYP) 3A4, e.g. rifampicin (rifampin) and phenytoin
      should not be combined with nisoldipine CC, as they may reduce its
      bioavailability and result in a loss of efficacy. The concomitant use of other
      drugs which may produce marked induction or inhibition of CYP3A4 is
      contraindicated. Concomitant intake of the CC tablet with high fat, high calorie
      foods resulted in an increase in the maximum plasma concentrations of
      nisoldipine. The 'food-effect' can be avoided by administration of the CC tablet
      up to 30 minutes before the intake of food [corrected]. Plasma concentrations of
      nisoldipine are related to its antihypertensive effect via a maximum effect
      model. Nisoldipine CC once daily produce reductions in blood pressure which are
      maintained over 24 hours in the absence of relevant effects on heart rate.

PMID- 9784936
TI  - Leptin: physiology and pathophysiology.
AB  - The identification and sequencing of the ob gene and its product, leptin, in late
      1994 opened new insights in the study of the mechanisms controlling body weight
      and led to a surge of research activity. During this time, a considerable body of
      knowledge regarding leptin's actions has been accumulated and the field continues
      to expand rapidly. Currently there is particular interest in the interaction of
      leptin with other peripheral and neural mechanisms to regulate body weight,
      reproduction and immunological response. In this review, we attempt to place the
      current state of knowledge about leptin in the broader perspective of physiology,
      including its structural characteristics, receptors, binding proteins, signalling
      pathways, regulation of adipose tissue expression and production, secretion
      patterns, clearance mechanisms and functional effects. In addition, leptin's
      involvement in the pathophysiology of obesity, anorexia nervosa, diabetes
      mellitus, polycystic ovary syndrome, acquired immunodeficiency syndrome, cancer,
      nephropathy, thyroid disease, Cushing's syndrome and growth hormone deficiency
      will be reviewed.

PMID- 9784938
TI  - Determination of blood flow in the finger using near-infrared spectroscopy.
AB  - Wavelengths in the near-infrared range have much better penetrance in organic
      substances than visible light. We used near-infrared spectroscopy to determine
      non-invasively blood flow in the fingertip. We used laser Doppler technology to
      measure skin blood flow as a comparison procedure. We performed several
      manoeuvres to change blood flow. These included restriction of flow, thermal
      stimulation and post-occlusion hyperaemia. Near-infrared measurements had
      coefficients of variation of 10-15% at the various wavelengths, contrasting with
      variability of 30-40% with laser Doppler measurement. With restriction of blood
      flow, there was a downward shift in the absorbance curve. With thermal
      stimulation and with post-occlusion hyperaemia, there was a rise in the curve.
      The flow-induced shifts in the absorbance curve were particularly pronounced in
      the range of 850-970 nm. The correlation between absorbance values and laser
      Doppler-determined blood flow was also highest in this range, averaging about
      0.69 (n = 625). Near-infrared spectroscopy can therefore be used to scan the
      fingertip. The absorbances obtained do reflect changes in blood flow. There is a
      correlation with skin blood flow, although near-infrared measurements are
      affected by blood flow in the full breadth of the finger, not just the skin. We
      can measure this blood flow with significant reproducibility. It may be possible
      to use near-infrared spectroscopy to measure the concentration of individual
      blood components.

PMID- 9784937
TI  - Whole-body cooling increases plasma endothelin-1 levels in women with primary
      Raynaud's phenomenon.
AB  - To understand better the role of endothelin-1 (ET-1) in the pathogenesis of
      primary Raynaud's phenomenon (PRP), we investigated the basal ET-1 plasma levels
      and changes after whole-body cooling in healthy women and those with PRP. The
      study was performed as an open parallel-group comparison during the month of
      February. The Raynaud group included 21 female patients (mean age 45.3 years,
      range 21-57 years) who had had disabling Raynaud's phenomenon for a mean period
      of 17 years (range 2-26 years). The control group consisted of 25 healthy women
      (mean age 43.6 years, range 27-56 years). Plasma levels of ET-1 were measured on
      two separate occasions: once after 30 min of rest at room temperature and after
      40 min of whole-body cooling. There were no significant differences in baseline
      plasma ET-1 levels between the two groups of women. The plasma ET-1 levels
      increased significantly in the PRP group after cold exposure (mean difference
      0.11 pmol l-1, 95% CI 0.005-0.214, P = 0.012). In contrast, the levels of plasma
      ET-1 in the control group did not change significantly after cold provocation. In
      conclusion, no differences in plasma basal levels of ET-1 were observed between
      the two groups. However, women suffering from Raynaud's phenomenon responded with
      a slight but significant elevation in plasma levels of ET-1 after whole-body
      cooling, whereas the healthy control subjects did not. The results from the
      present study confirm previous observations that endothelial dysfunction may be
      of aetiological importance in PRP.

PMID- 9784934
TI  - Pharmacokinetic alterations after severe head injury. Clinical relevance.
AB  - Pharmacological therapy, present and future, will undoubtedly continue to play a
      large role within the overall management of patients with severe head injury.
      Nevertheless, limited clinical data are available to evaluate the effect of
      severe head injury on pharmacokinetics. The disruption of the blood-brain barrier
      secondary to trauma and/or subsequent hyperosmolar therapy can be expected to
      result in higher than expected brain drug concentrations. Aggressive dietary
      protein supplementation may result in increased oxidative drug metabolism. These
      effects may counterbalance inhibitory influences on drug metabolism secondary to
      cytokine release during the acute phase response. Alterations in protein binding
      can also be anticipated with the hypoalbuminaemia and increases in alpha 1-acid
      glycoprotein typically observed in these patients. Based on studies in other
      patient populations, moderate hypothermia, a treatment strategy in patients with
      head injury, can decrease drug metabolism. The pharmacokinetics of the following
      drugs in patients with severe head injury have been studied: phenytoin,
      pentobarbital (pentobarbitone), thiopental (thiopentone), tirilazad, and the
      agents used as marker substrates, antipyrine, lorazepam and indocynanine green
      (ICG). Several studies have documented increase in metabolism over time with
      phenytoin, pentobarbital, thiopental, antipyrine and lorazepam. Increases in
      tirilazad clearance were also observed but attributed to concurrent phenytoin
      therapy. No changes in the pharmacokinetics of ICG were apparent following head
      injury. With the frequent use of potent inhibitors of drug metabolism (e.g.,
      cimetidine, ciprofloxacin) the potential for drug interaction is high in patients
      with severe head injury. Additional pharmacokinetic investigations are
      recommended to optimise pharmacological outcomes in patients with severe head
      injury.

PMID- 9784935
TI  - Pharmacokinetic optimisation of the treatment of bacterial central nervous system
      infections.
AB  - Central nervous system (CNS) infections caused by bacteria with reduced
      sensitivity to antibacterials are an increasing worldwide challenge. In
      successfully treating these infections the following conditions should be
      considered: (i) Antibacterials do not distribute homogeneously in the central
      nervous compartments [cerebrospinal fluid (CSF), extracellular space of the
      nervous tissue, intracellular space of the neurons, glial cells and leucocytes].
      Even within the CSF, after intravenous administration, a ventriculo-lumbar
      concentration gradient is often observed. (ii) Valid parameters of drug entry
      into the CSF are the CSF: serum concentration ratio in steady state and the CSF:
      serum ratio of the area under the concentration-time curves (AUCCSF/AUCS).
      Frequently, the elimination half-life (t1/2 beta) in CSF is longer than t1/2 beta
      in serum. (iii) For most antibacterials, lipophilicity, molecular weight and
      serum protein binding determine the drug entry into the CSF and brain tissue.
      With an intact blood-CSF and blood-brain barrier, the entry of hydrophilic
      antibacterials (beta-lactam antibacterials, glycopeptides) into the CNS
      compartments is poor and increases during meningeal inflammation. More lipophilic
      compounds [metronidazole, quinolones, rifampicin (rifampin) and chloramphenicol]
      are less dependent on the function of the blood-CSF and blood-brain barrier. (iv)
      Determination of the minimal inhibitory concentrations (MIC) of the causative
      organism is necessary for optimisation of treatment. (v) For rapid sterilisation
      of CSF, drug concentrations of at least 10 times MIC are required. The minimum
      CSF concentration: MIC ratio ensuring successful therapy is unknown. Strategies
      to achieve optimum antibacterial concentrations in the presence of minor
      disturbances of the blood-CSF and blood-brain barrier include, the increased use
      of low toxicity antibacterials (e.g., beta-lactam antibiotics), the use of
      moderately lipophilic compounds, and the combination of intravenous and
      intraventricular administration. Antibacterials which do not interfere with
      bacterial cell wall synthesis delay and/or decrease the liberation of
      proinflammatory bacterial products, delay or inhibit tumour necrosis factor
      release, and may reduce brain oedema in experimental meningitis. Conclusive
      evidence of the reduction of neuronal damage by this approach, however, is
      lacking.

PMID- 9784939
TI  - Inhomogeneity in planar ventilation scintigraphy of emphysematous patients.
AB  - The aim of this study was to develop and evaluate a method for the quantification
      of inhomogeneity in ventilation scintigraphy. Ten healthy volunteers and 10
      emphysematous patients were investigated. Anteroposterior (AP) and
      Posteroanterior (PA) images of planar ventilation scintigraphy were acquired.
      Lung regions of interest (ROI) were obtained by manual delineation of the lung
      contours and then divided into several 10-pixel-high horizontal-stripe regions.
      By allowing for the statistical noise of the pixel count rate, the biological
      coefficient of variation (CVB) of the pixel counts in each stripe region was
      calculated. The apex-to-base distribution of the CVB in the emphysematous lungs
      dispersed largely and with higher values than the corresponding distribution in
      the healthy lungs. The mean values of the CVB (MCVB), the ranges of the CVB
      (RCVB) and the maximum values of the CVB (MAXCVB) in the stripe regions in
      emphysematous lungs were significantly higher than the corresponding ones in the
      healthy lungs (all P < 0.001). The intraobserver variations of the MCVB, RCVB and
      MAXCVB (calculated using the standard deviations of the differences) were less
      than 2.3% units, 5.2% units and 3.9% units respectively. The corresponding values
      for interobserver variation were 5.7% units, 6.1% units and 6.4% units. A
      systematic decrease in lung ROI size, i.e. inclusion of successively less of the
      lung edge, resulted in a linear decrease of 1.7% units in the MCVB and MAXCVB of
      both emphysematous and normal lungs. In conclusion, the stripe-region method is a
      reliable tool for the quantification of inhomogeneity in the planar ventilation
      scintigraphy.

PMID- 9784940
TI  - The venoarteriolar response of the skin in healthy legs measured at different
      depths.
AB  - The venoarteriolar response (VAR) of the skin in healthy legs of 20 subjects was
      investigated. The laser Doppler flux (LDF), at an experimental venous
      hypertension of 30 mmHg, 45 mmHg and 60 mmHg, produced by a pneumatic cuff around
      the thigh in a recumbent position, was compared with the LDF in a sitting
      position. The LDF of the skin was measured simultaneously at the same site of the
      superficial capillary layer (with 543 nm) and of the deeper capillary layer (with
      780 nm). At 543 nm the LDF did not differ significantly at any cuff pressure from
      the LDF recorded in a sitting position, whereas at 780 nm the LDF was
      significantly higher at the cuff pressure of 30 mmHg than the LDF in a sitting
      position (P = 0.002). The VAR was much weaker at 543 nm than at 780 nm, and the
      scatter of the VAR values was high. In a sitting position the VAR at 543 nm was
      9.3% and at 780 nm 34.6% (P < 0.001). The VAR at 543 nm at the cuff pressure of
      30 mmHg did not differ significantly from the VAR caused by the sitting position,
      whereas at 780 nm the VAR at the cuff pressure of 30 mmHg was significantly less
      than the VAR caused by the sitting position (P = 0.001). Despite the high scatter
      of the VAR values, these findings suggest that the VAR in the superficial
      capillary layer is smaller, and that it reached maximum at lower venous
      hypertension, than the VAR in the deeper capillary layer.

PMID- 9784941
TI  - Thoracoabdominal asynchrony in small children with lung disease--methodological
      aspects and the relationship to lung mechanics.
AB  - Thoracoabdominal asynchrony (TAA) has been regarded as a clinical sign of lung
      disease. A measure of TAA is the phase angle (phi) between ribcage (RC) and
      abdominal (ABD) respiratory motion. The aim of this study was to assess the
      effect of the points chosen for phi calculation. The influence of correct
      respiratory timing was assessed by calculating TAA indices using a
      pneumotachometer (PTM) as timing reference and using the calibrated respiratory
      inductive plethysmograph (RIP) signal for respiratory timing. The relationship
      between TAA and lung mechanics was studied in 15 young children 9 months to 2.5
      years of age with a wide span of restrictive and/or obstructive lung disease. phi
      as calculated from mid-RC points was poorly related to phi as calculated from the
      top RC and ABD positions, indicating non-sinusoidal respiratory motions. The
      estimation of the TAA indices depended on correct respiratory timing, which in
      the case of severe asynchrony cannot be inferred from the RIP signals alone. An
      external source for respiratory timing, such as the airway flow measured by a
      PTM, is needed. The degree of asynchronous chest wall movement was only a weak
      indicator of pathological lung mechanics. We conclude that the usefulness of TAA
      indices as indicators of impaired lung mechanics is limited by the sensitivity to
      the points used for their calculation (phi) and the need of an external source
      for respiratory timing. It was therefore not surprising that a rather weak
      relationship was seen between TAA indices and lung mechanics.

PMID- 9784942
TI  - Exaggerated blood pressure response to exercise: importance of resting blood
      pressure.
AB  - Normotensive individuals who exhibit an exaggerated blood pressure (BP) response
      to exercise have an increased risk of future hypertension. However, previous
      studies failed to control for resting BP despite the fact that an elevated
      resting BP in the normotensive range is also a strong predictor of future
      hypertension. Therefore, we determined whether maximal systolic BP is associated
      with resting BP. Resting BP was measured in 68 healthy normotensive men on three
      separate days. The subjects then performed a graded, maximal exercise test on a
      Monark cycle ergometer. Maximal systolic BP was strongly correlated with resting
      systolic BP (r = 0.64, P < 0.0001). Subjects with elevations in systolic BP
      during maximal exercise (> 220 mmHg) also had higher (P < 0.005) resting BP than
      those without (< 220 mmHg). When stepwise regression analyses were performed,
      systolic BP at rest was a significant independent predictor of maximal systolic
      BP, explaining over 40% of the variability. These results suggest that
      exaggerated BP response as a predictor of future hypertension reported in
      previous studies may be little more than a simple reflection of elevated resting
      BP. Specifically, these studies should not be interpreted as demonstrating that
      exercise BP is a better predictor of future hypertension than resting BP alone.
      In the future, defining the BP 'response' to exercise as a change score (i.e.
      maximal BP minus resting BP) may be advantageous as it permits the effects of
      exercise to be examined independently of the level of resting BP.

PMID- 9784943
TI  - Left ventricular geometry and function are related to electrocardiographic
      characteristics and diagnoses.
AB  - We investigated the relationships between echocardiographic indices of left
      ventricular geometry and function and major electrocardiographic (ECG)
      abnormalities in 540 elderly (69-74 years old) male participants of a health
      survey conducted in Uppsala county, Sweden. Comparing men with major ECG
      abnormalities that were present or absent in various hierarchic mutually
      exclusive categories, left ventricular mass indexed to body surface area (LVMI)
      was significantly increased with major Q-waves (P = 0.0002), ST or T-wave
      abnormalities (P = 0.005), left bundle-branch block (P = 0.005) and also with
      atrioventricular block type 1 (P = 0.008) and frequent premature beats (P =
      0.02). The left atrial diameter was also significantly increased with most ECG
      abnormalities. The increased LVMI was in left bundle-branch block mainly due to
      an increased left ventricular diameter, whereas left ventricular wall thickness
      was increased with frequent premature beats, atrioventricular block type 1 and ST
      or T-wave abnormalities. The prevalence of Q-waves was highest in eccentric left
      ventricular hypertrophy, whereas the prevalence of ST or T-wave abnormalities and
      atrioventricular block type 1 was highest in concentric left ventricular
      hypertrophy. Both left ventricular systolic (ejection fraction) and diastolic
      function (E/A) ratio) were inversely related to Sokolow-Lyon QRS amplitude (r = 
      0.25, P < 0.02 and r = -0.22, P < 0.03 respectively). In conclusion, LVMI was
      increased in subjects with ECG signs of coronary artery disease as well as in
      subjects with several other ECG diagnoses. Furthermore, both left ventricular
      systolic and diastolic dysfunction were related to increased QRS amplitudes.
      Thus, the finding of ECG abnormalities in elderly men should raise the suspicion
      of structural and/or functional left ventricular abnormality.

PMID- 9784944
TI  - Respiratory-like periodicities in slow eye movements during sleep onset.
AB  - Slow eye movements (SEMs) during sleep onset and their relationship to vegetative
      rhythms were investigated in six healthy, sleep-deprived subjects, yielding 143
      289 SEMs in an epoch of 31.5-56 min per experiment. Exclusively, sleep in stages
      I and II was recorded. From the bandpass-filtered electro-oculogram (EOG) signal
      (cut-off frequencies 0.05 and 1 Hz), turning points of the gaze were detected and
      compared with the start of inspiration, which was discriminated from the
      abdominal respiratory excursions. SEM cycle times varied considerably more than
      respiratory cycle times (P < 0.05 in Levene's test). Both were preferentially of
      equal length, or, in some subjects, in 2:1 co-ordination. Cross-correlation
      histograms yielded that inspiration and SEMs were also temporally co-ordinated.
      Thus, there is a temporal coherence regarding the occurrence, the cycle time and
      the phase between SEMs and a respiratory-like rhythm. Our findings show that it
      is not exactly the respiratory rhythm that is mirrored in the SEMs. Rather, we
      favour the interpretation of an autorhythmicity that is temporarily connected to
      the common brainstem system in the reticular formation of the brainstem.

PMID- 9784945
TI  - Reproducibility of ultrasonic fetal volume blood flow measurements.
AB  - The intraobserver reproducibility of ultrasonic volume blood flow measurements in
      the human fetus was evaluated in this study. A new approach, simultaneous
      measurement of the vessel diameter and the flow velocity with a pulsed-wave
      Doppler ultrasound synchronized with a real-time ultrasound phase-locked echo
      tracking system, was used to estimate volume blood flow (VBF) in the fetal
      descending aorta. Measurements were performed in a longitudinal study on 20
      normally grown fetuses. Intraobserver reproducibility of repeated estimations of
      mean blood flow velocities throughout gestation was very good, with high values
      of intraclass correlation coefficient (IntraCC 0.80-0.91) and low values of
      coefficient of variation (CV 4-11%). The IntraCC of repeated vessel diameter
      measurements throughout gestation was low (0.30-0.68), whereas the values of CV
      were acceptable (< 12%), with the exception of the period between 140 and 167
      gestational days (CV > 12%). The lower reproducibility of vessel diameter
      measurement contributed directly to the relatively low reproducibility of VBF
      estimations overall (IntraCC 0.25-0.70; CV 17-28%), as these are calculated from
      a formula using both flow velocity and vessel diameter. Nevertheless, the
      synchronized approach gives absolute values of vessel diameter, flow velocity and
      VBF comparable with values reported in the human fetus previously. The new method
      provides, by taking the vessel wall pulsations into consideration and by
      measuring diameter and velocity simultaneously, a more complete information on
      fetal haemodynamics and fetal physiology.

PMID- 9784946
TI  - Inflammatory bowel disease in the pregnant woman.
AB  - Pregnant women with inflammatory bowel disease and their physicians should be
      aware of factors that may affect the outcome of the pregnancy. Proper patient
      education, along with a physician team approach, usually ensure completion of an
      uneventful pregnancy.

PMID- 9784947
TI  - 10 questions about Lyme neuroborreliosis.
AB  - The diagnosis of Lyme neuroborreliosis requires a high index of suspicion and
      chronological correlation of the clinical findings and laboratory data. The
      limitations of serologic tests must be understood. Cerebrospinal fluid anti
      Borrelia burgdorferi antibody index is currently the best indicator of Lyme
      neuroborreliosis.

PMID- 9784949
TI  - PFT principles and bronchodilator testing in clinical practice: a guide for
      primary care physicians.
AB  - Pulmonary function tests (PFTs) are frequently employed by primary care
      physicians in diagnosis and treatment. This paper reviews several basic concepts
      and addresses selected misconceptions about PFTs, focusing on bronchodilator
      testing and clinical decision-making.

PMID- 9784948
TI  - Wegener's granulomatosis: controversies and current concepts.
AB  - Wegener's granulomatosis, the most common of the pulmonary granulomatous
      vasculitides, may affect virtually any organ. Complications resulting from
      chronic cytotoxic therapy have led to novel treatment strategies. These
      alternative therapeutic modalities are promising, but additional studies are
      required to define their roles.

PMID- 9784950
TI  - Practical approach to the diagnosis and treatment of esophageal dysphagia.
AB  - In 80% to 85% of patients with esophageal dysphagia, careful history can help
      identify the cause. There are a wide range of treatments, including surgery, that
      can return patients to normal swallowing.

PMID- 9784951
TI  - Escalating health care costs: costs of litigation.
AB  - Although controlling the risks and costs of litigation is difficult, that goal is
      worth pursuing. Trumped-up malpractice claims, direct litigation costs, and
      defensive medicine contribute to the accelerating costs of U.S. health care but
      are not their driving force.

PMID- 9784952
TI  - Accuracy of registration methods in frameless stereotaxis.
AB  - The accuracy of image to patient registration is a critical issue in the
      intraoperative use of frameless stereotaxic instruments for surgical guidance.
      This study was performed to assess the accuracy of image to head phantom
      registration using several standard registration techniques and a clinical
      frameless stereotaxic instrument. Two types of radioopaque fiducial markers were
      fixed to a plastic head phantom, and a computed tomography scan of the phantom
      was performed in the routine fashion. Image to phantom registration was carried
      out using fiducial markers, fiducial markers plus surface fit, anatomic
      landmarks, and anatomic landmarks plus surface fit. After each registration,
      linear inaccuracy measurements were performed for each of 32 markers. Each
      registration was performed 10 times, and the overall mean error measurements and
      anterior and posterior error were computed and compared. The overall mean error
      was smallest for the fiducial registration alone (2.07 mm). The magnitude of
      error increased significantly for posterior locations for all other registration
      techniques, but it was not significantly increased for the fiducial registration
      method. For this hardware configuration, registration with surface-applied
      fiducial markers is measurably more accurate than registration with surface
      anatomic landmarks. The addition of surface points to the fiducial registration
      does not increase the registration accuracy but, in fact, increases the degree of
      error.

PMID- 9784953
TI  - Interactive image-guided surgical resection of intracranial arteriovenous
      malformations.
AB  - Surgical excision is the only treatment method that immediately prevents
      increased morbidity or mortality as a result of hemorrhage from arteriovenous
      malformations (AVMs). For those lesions located deep within the cerebral
      hemispheres or near eloquent areas, conventional surgical resection may be
      associated with an unacceptable degree of morbidity and mortality. Herein we
      report our experience in the resection of these lesions using interactive image
      guidance. There were five women and five men in the patient group. Their age
      ranged from 16 to 73 years (mean = 41). Clinical presentation included hemorrhage
      (n = 7), headaches (n = 2), and seizures (n = 1). All lesions were classified
      using the Spetzler-Martin grading system as follows: grade I (n = 4), grade II (n
      = 5), and grade III (n = 1). The locations of the lesions were supratentorial (9)
      and infratentorial (1). Surgical planning was carried out using the Neurological
      Surgery Planning System software developed at Wayne State University. An infrared
      based system was used to locate and define the lesion intraoperatively. For those
      lesions located near or within eloquent areas, an awake craniotomy with
      functional mapping was carried out. Clinical follow-up ranged from 3 to 62 months
      (mean = 34). Complete surgical excision was achieved in all patients, which was
      demonstrated postoperatively by digital substraction angiography. The
      preoperative neurological status remained unchanged in seven patients and
      improved in three. There was no associated morbidity and mortality with this
      technique. Image-guided surgical resection of arteriovenous malformations
      represents a valuable technique, especially in small deep-seated lesions and in
      those near eloquent areas.

PMID- 9784954
TI  - Intraoperative localization of functional regions in the sensorimotor cortex by
      neuronavigation and cortical mapping.
AB  - Surgery of lesions within the central region requires exact intraoperative
      anatomical orientation and knowledge of the position of functional cortical
      regions to minimize the surgical trauma and to avoid postoperative neurological
      deficits. We combined somatosensory evoked potential (SSEP) phase reversal and/or
      cortical electrical stimulation with neuronavigation in 26 patients for
      localization and visualization of functional cortical areas and their anatomical
      site in relation to the lesion. After location of the central sulcus by means of
      SSEP phase reversal, the precentral gyrus was electrically stimulated to detect
      functional motor regions. Electrode position was documented, and the functional
      regions were related to the site of the lesion using a specially developed
      neuronavigation system. In 11 of 15 patients the central fissure was located with
      SSEP phase reversal. Electrical stimulation yielded motor evoked potentials in 23
      of the total 26 patients. The anatomical site of these functional regions and
      their relation to the lesion were evaluated with the neuronavigation system. The
      precentral gyrus, central sulcus, and postcentral gyrus could be identified in
      all 23 cases. The combination of intraoperative electrophysiological mapping and
      neuronavigation provides safe and reliable localization of the sensorimotor
      cortex. This technique is a promising tool to minimize the risk of surgically
      caused sensory and motor deficits.

PMID- 9784955
TI  - Objective method for localization of cortical asymmetries using positron emission
      tomography to aid surgical resection of epileptic foci.
AB  - We designed a semiautomated method for the objective detection of abnormal
      regions of tracer accumulation in the brain. The purpose of the present study was
      to examine the diagnostic performance of this method by applying it to patients
      with clinically intractable epilepsy of unilateral origin; they underwent [F-18]
      deoxyglucose positron emission tomography (PET) prior to surgical resection of
      epileptic foci. A semiautomated method for assessment of asymmetries in the brain
      cortex was developed that compares activity concentrations in homotopic cortical
      areas. When these differences exceeded a predefined threshold, the areas with
      lower activity were marked and 3-dimensional surface rendered images were created
      to guide placement of intracranial electrodes (ECoG) followed by surgical
      resection. The normal amount of asymmetry between small (0.5-0.7 cm2) homotopic
      cortical regions was determined as 5.9 +/- 4.0% (mean +/- SD). The false-positive
      fraction was determined for cutoff thresholds of 1 SD (10%), 1.5 SD (12%), and 2
      SD (15%) outside the mean and was found to be 89, 44, and 0%, respectively. The
      obtained sensitivity-specificity pairs for correct localization of epileptogenic
      lobes based on the ECoG results were best for the 15% threshold (80/94%, accuracy
      0.90). This objective PET method allows the accurate determination of cortical
      asymmetries, and it proved to be highly efficient in guiding epilepsy surgery.

PMID- 9784956
TI  - Tracing of thin tubular structures in computer tomographic data.
AB  - For many applications in diagnostics and in the planning of surgical
      interventions, specific structures have to be identified in a patient's volume
      data set. In this article we give an outline of how the detection of thin tubular
      structures (e.g., nerves and vessels) can be automated, requiring very little
      initialization from a human expert. We focused on the nervus alveolaris inferior
      in the lower jaw and were looking at three details: data acquisition, detection,
      and validation of accuracy. Our method can be easily adapted to many similar
      cases such as other nerves, arteries, and veins or bundles thereof.

PMID- 9784957
TI  - Three-dimensional computed tomographic reconstruction: planning tool for surgery
      of skull base pathologies.
AB  - Three-dimensional (3-D) computed tomographic (CT) reconstruction of the skull
      base region has added a different perspective to the data set usually presented
      in axial or coronal slices. It simultaneously demonstrates the spatial
      relationship of bones, tumors, vessels, and ventricles in a single illustration.
      Forty-nine patients with skull base lesions (44 with neoplastic and 5 with
      vascular pathologies) were examined with a spiral CT and 3-D reconstruction prior
      to surgery. A scanner and a maximum of 95 mL of iodized contrast media were used
      to enhance either tumor or vessels according to the specific pathology.
      Preoperative 3-D reconstruction was performed. It rendered a spatial
      representation of the pathology using data similar to that usually acquired in
      routine preoperative diagnostics. Complex anatomy can be visualized with only a
      handful of pictures. It was possible to easily compare various surgical
      approaches to the lesion on the basis of the 3-D computer model and to simulate
      the surgeon's view. The short time span (1 h average) necessary for
      reconstruction and editing allows the application of this method as a routine
      preoperative procedure for selected skull base pathologies.

PMID- 9784958
TI  - Soft tissue rapid prototyping in neurosurgery.
AB  - As part of our research into the fluid hydrodynamics of the human ventricular
      system, a fused deposition model of the human ventricular system was made using
      magnetic resonance imaging (MRI) data. This article describes the manufacturing
      of a positive cast of the ventricles as a first step in the construction of a
      hollow model. After decryption of the original MRI file (ACR-Nema format), the
      MRI slices were reassembled semiautomatically and a rapid prototyping station
      produced a resin model. Because of its ease and speed, this method harbors great
      potential for teaching purposes, research, and preoperative planning in complex
      three-dimensional soft tissue targets.

PMID- 9784959
TI  - The forced expiratory volume-time curve estimation using the electrocardiogram.
AB  - The feasibility of estimating the forced expiratory volume-time curve from the
      amplitude modulation of the electrocardiogram was studied using a numerical torso
      model and ECG signal processing. A two dimensional numerical model of the torso
      was solved for the maximum expiration and inspiration to study the changes in the
      surface potential as a result of changes in the lung volume. The numerical model
      showed that significant changes in the surface potential amplitude occur between
      maximum inspiration and maximum expiration and that this amplitude change in the
      left-right axis of the torso might be three times as large as in the front-back
      axis. In the experimental setup, ECG waveforms from the surface of the chest and
      the mouth air flow were simultaneously recorded from four male subjects during
      several forced vital capacity (FVC) maneuvers. The amplitude of the QRS complex
      was measured for different expired lung volumes and an estimation of the forced
      expiratory volume-time curve was obtained. The FVC and the FEV1 (forced
      expiratory volume after 1 s) spirometry indices were calculated for the two
      volume-time curves obtained from the electrocardiogram and from the spirometry
      measurements. The results differ between 0.1 and 0.8 1. These preliminary results
      are encouraging and might indicate that a relationship between the volume-time
      curve during FVC test and the electrocardiogram signals does exist. Further
      validation in a larger number of subjects and patients is needed before the
      technique can be applicable for clinical use.

PMID- 9784960
TI  - New closed-form expressions for the estimation of arterial windkessel compliance.
AB  - New closed-form mathematical expressions, in the time- and frequency-domain, are
      derived for estimating the arterial windkessel compliance. The proposed
      expressions assume the three-element windkessel to model the arterial system and
      require the measurements of the entire waveforms of arterial pressure and flow.
      The resistance parameters are estimated using the recently proposed energy
      balance method, then compliance is analytically calculated in order to minimize
      the pressure error in the compliant element. The derived expressions remain valid
      even when the windkessel compliance is assumed to be pressure-dependent. Also, it
      is shown that the method, either time- or frequency-domain formulation, provides
      parameter estimates, which minimize the arterial pressure square error. The
      method has been applied to simulated data as well as to pressure and flow data
      measured in the ascending aorta of three anaesthetized dogs under different
      circulatory conditions.

PMID- 9784961
TI  - A comparison of computer based classification methods applied to the detection of
      microaneurysms in ophthalmic fluorescein angiograms.
AB  - We compared the performance of three computer based classification methods when
      applied to the problem of detecting microaneurysms on digitised angiographic
      images of the retina. An automated image processing system segmented 'candidate'
      objects (microaneurysms or spurious objects), and produced a list of features on
      each candidate for use by the classifiers. We compared an empirically derived
      rule based system with two automated methods, linear discriminant analysis and a
      learning vector quantiser artificial neural network, to classify the objects as
      microaneurysms or otherwise. ROC analysis shows that the rule based system gave a
      higher performance than the other methods (p = 0.92) although a much greater
      development time is required.

PMID- 9784962
TI  - A 3D deformable surface model for segmentation of objects from volumetric data in
      medical images.
AB  - In this paper we present a new 3D discrete dynamic surface model. The model
      consists of vertices and edges, which connect adjacent vertices. Basic geometry
      of the model surface is generated by triangle patches. The model deforms by
      internal and external forces. Internal forces are obtained from local geometry of
      the model and are related to the local curvature of the surface. External forces,
      on the other hand, are based on the image data and are calculated from desired
      image features. We also present a method for generating an initial volume for the
      model from a stack of initial contours, drawn by the user on cross sections of
      the volumetric data.

PMID- 9784963
TI  - 2 barrier-1 site pore: an interactive spreadsheet model for two permeating ions.
AB  - An interactive ion channel permeation tutorial was developed using a Microsoft
      Excel v5.0 spreadsheet to describe a two barrier, one site channel model by means
      of Eyring rate theory (ERT). The spreadsheet is inherently interactive so that
      the user receives immediate feedback about how changes in the energy barrier
      profile or ion concentrations affect current-voltage relations and single channel
      conductance. The spreadsheet model is easy to use, allows direct access to
      intermediate calculated values and all equations, contains graphical displays of
      parameters and lends itself to customization by a user having only a basic
      knowledge of spreadsheet operations.

PMID- 9784965
TI  - Optimization and mechanism of step-leap respiration exercise in treating of cor
      pulmonale.
AB  - The interaction between cardiovascular system and the respiratory system is
      complicated and may be used for the rehabilitation of the cor pulmonale disease.
      To study the effects of different breathing mode on the cardiac and pulmonary
      systems, a mathematical model is established based on the previous work. Using
      this model, computer simulation experiments are carried out for searching an
      optimal respiration mode in treating of cor pulmonale disease. Results indicate
      that the step-leap respiration mode could provide a better assistant to the
      rehabilitation of the cor pulmonale patients in the sense of increasing coronary
      flow, reducing pulmonary arterial pressure and reducing the working load for the
      right heart. This result is also proven by the clinical experiments. This work
      may suggest that a proper directed respiration exercise can be used in the
      treatment of cor pulmonale disease.

PMID- 9784964
TI  - Visual classification of medical data using MLP mapping.
AB  - In this work we discuss the design of a novel non-linear mapping method for
      visual classification based on multilayer perceptrons (MLP) and assigned class
      target values. In training the perceptron, one or more target output values for
      each class in a 2-dimensional space are used. In other words, class membership
      information is interpreted visually as closeness to target values in a 2D feature
      space. This mapping is obtained by training the multilayer perceptron (MLP) using
      class membership information, input data and judiciously chosen target values.
      Weights are estimated in such a way that each training feature of the
      corresponding class is forced to be mapped onto the corresponding 2-dimensional
      target value.

PMID- 9784966
TI  - Unsupervised connectivity-based thresholding segmentation of midsagittal brain MR
      images.
AB  - In this paper, we propose an algorithm for automated segmentation of midsagittal
      brain MR images. First, we apply thresholding to obtain binary images. From the
      binary images, we locate some landmarks. Based on the landmarks and anatomical
      information, we preprocess the binary images, which substantially simplifies the
      subsequent operations. To separate regions what are incorrectly merged after this
      initial segmentation, a new connectivity-based threshold algorithm is proposed.
      Assuming that some prior information about the general shape and location of
      objects is available, the algorithm finds a boundary between two regions using
      the path connection algorithm and changing the threshold adaptively. In order to
      test the robustness of the proposed algorithm we applied the algorithm to 120
      midsagittal brain images and obtained satisfactory results.

PMID- 9784967
TI  - CD28/B7 costimulation: a review.
AB  - The current model of T cell activation requires two signals. The first signal is
      specific, requiring T cell receptor recognition and binding to MHC/Antigen
      presented by an antigen-presenting cell. The second signal is nonspecific,
      resulting from the binding of B7 ligand on the antigen-presenting cell with its
      receptor, CD28, on the T cell. If both signals are provided, the T cell will
      proliferate and secrete cytokines. Recently, it has been shown that CTLA4,
      another receptor for B7 that is upregulated following T cell after activation,
      can deliver an inhibitory signal, downregulating T cell proliferation. The B7
      family of ligands has two family members, B7-1 and B7-2. They both bind to CD28
      and CTLA4, but they differ in their binding affinity, structure, and temporal
      expression. Considerable research has been done on the CD28/B7 costimulatory
      pathway. Different ways of manipulating this pathway could provide insights into
      the mechanism and treatment of opposing pathological states. Blocking the CD28/B7
      pathway could result in immunosuppression, with implications for the treatment of
      autoimmune diseases, organ transplantation, and graft vs. host disease.
      Activating the CD28/B7 pathway could be useful for including the immune system to
      recognize and eliminate tumors that evade the immune system. Finally, the CD28/B7
      pathway could be involved with maintaining immune tolerance, as recent studies
      suggest the preferential binding of the B7-CTLA4 pathway results in the down
      regulation of the responding T cells. Thus, the B7/CD28/CTLA4 pathway has the
      ability to both positively and negatively regulate immune responses.

PMID- 9784968
TI  - Ca2+ signaling in T-lymphocytes.
AB  - Ca2+ signaling in response to antigenic stimulation is essential for
      proliferation of T cells and therefore is one of the important early events in T
      lymphocyte signal transduction. Several aspects of T cell receptor/CD3 complex
      stimulated Ca2+ signaling are reviewed: generation, metabolism, function, and
      intracellular targets of the Ca(2+)-mobilizing second messengers inositol 1,4,5
      trisphosphate and cyclic ADP-ribose, the mechanism of Ca2+ entry, and the
      generation of Ca2+ oscillations on the single cell level. In addition, Ca2+
      signaling induced by further stimuli is discussed, including other T-lymphocyte
      surface receptors (e.g., CD4 or beta 1-integrins, lipids, and physical stimuli).

PMID- 9784969
TI  - DNA vaccines.
AB  - DNA vaccination against infectious diseases has created a new field of applied
      molecular immunology. cDNAs for 'protective' protein epitopes can be inserted
      into vectors containing strong mammalian promoters for high expression. Here we
      discuss the mechanisms of DNA vaccination and the successful and sometimes
      unsuccessful applications of DNA vaccination to protect animals against many
      different viral, bacterial mycoplasmal, protozoal, and worm infections or
      infestations. DNA immunization has been used to prevent or inhibit tumor
      development and to inhibit IgE responses by diverting the immune response from
      Th2 to Th1 helper cell dominance. Advantages and disadvantages of a variety of
      routes of administration and methods of immunization discussed include the use of
      the 'gene gun', the delivery of genes by aerosols, and deliberate induction of
      injury to muscles prior to injection of DNA to enhance gene expression.
      Vaccination performed using DNA without knowing beforehand the protective
      epitopes, using 'expression library immunization', is discussed. While this field
      is bound to expand rapidly for future clinical applications, we try to point out
      potential pitfalls as well as advantages of this relatively new technology.

PMID- 9784970
TI  - Heart disease and other causes of sudden death in young athletes.

PMID- 9784971
TI  - Pattern formation in zebrafish--fruitful liaisons between embryology and
      genetics.
AB  - Vertebrate embryos, despite quite diverse early morphologies, appear to employ
      similar cellular strategies and conserved biochemical pathways in their
      development (Eyal-Giladi, 1997). In the past decade, a small tropical teleost,
      zebrafish (Danio rerio), became an important model system in which to study
      development (Streisinger et al., 1981). By combining embryology with molecular
      and classical genetic methods, our understanding of early inductive and
      morphogenetic events during vertebrate embryogenesis significantly advanced. In
      zebrafish, dorsal-ventral polarity is established during early cleavage and is
      dependent on microtubular transport of determinants from the vegetal pole to the
      blastomeres positioned on top of the yolk cell. The syncytium forming from these
      marginal blastomeres in the early blastula exhibits dorsal-ventral asymmetry with
      beta-catenin localized to the nuclei on the presumptive dorsal side of the
      syncytium. The yolk cell is a source of signals that induce and pattern overlying
      blastoderm. Therefore, the dorsal yolk syncytial layer is equivalent to the
      Nieuwkoop center of the amphibian embryo. The embryonic shield, a thickening of
      the dorsal blastoderm margin, exhibits properties similar to the amphibian
      Spemann organizer. However, certain inductive and patterning signals from the
      organizer might be produced before the shield forms or might originate outside of
      the shield. Similar to the amphibian embryo, the key patterning functions of the
      fish dorsal organizer (i.e., dorsalization of mesoderm, ectoderm, and
      coordination of gastrulation movements) are performed by secreted molecules that
      antagonize the ventralizing activity of the swil (zbmp-2) and zbmp-4 gene
      products expressed on the ventral side of the embryo. These functions of the
      dorsal organizer require the activity of the chordino gene (a zebrafish homologue
      of chordin), bozozok, mercedes and ogon loci.

PMID- 9784972
TI  - Molecular and cellular basis of pattern formation during vertebrate limb
      development.
AB  - The body plan is generated by cells and tissues that become arranged precisely in
      the embryo. This process, termed pattern formation, involves cell interactions in
      which a particular group of cells produce signals that specify new cell types or
      patterns of differentiation in responding cells. These patterning signals emanate
      from very discrete centers called "organizer centers," such as the Hensen's node
      or Spemann organizer, the midbrain-hindbrain junction, the notochord, or in the
      case of the limb, the zone of polarizing activity (ZPA) or the apical ectodermal
      ridge (AER). The developing vertebrate limb is an ideal model system for the
      study of pattern formation because, in addition to surgical manipulations,
      molecular manipulations are now feasible. In this review we summarize early
      experiments that established, by means of surgical manipulations, the different
      organizer centers of the vertebrate limb: the ectoderm covering the limb bud, the
      apical ectodermal ridge, the zone of polarizing activity, and the distal mesoderm
      (progress zone) underlying the AER. We then describe the domains of expression of
      various genes present during the development of the limb and discuss some of the
      functional approaches (overexpression and lack of function studies) undertaken to
      ascertain their role in limb outgrowth. The knowledge acquired in the last few
      years has had an enormous impact not only on our view of how limbs develop
      (perhaps now one of the most approachable vertebrate model systems) but also in a
      more general sense of how the embryo is organized in space and time.

PMID- 9784973
TI  - Wise, winsome, or weird? Mechanisms of sperm storage in female animals.
AB  - Female sperm storage is an integral part of the reproductive pattern of many
      species. In the female, sperm become sequestered in specialized storage organs or
      reservoirs, where they may remain for several days, weeks, months, or years
      before being used to fertilize eggs. Several different but interrelated
      mechanisms are used by animals to target the sperm to the portion of the female
      genital tract adapted for sperm storage. Both males and females influence this
      process. This review describes themes among the mechanisms and molecules
      necessary for sperm to become efficiently stored in females and the roles that
      the female storage organs play in the nourishment, protection, and release of
      stored sperm.

PMID- 9784974
TI  - Developmental genetics of Caenorhabditis elegans sex determination.
AB  - The nematode Caenorhabditis elegans has two naturally occurring sexes: a self
      fertile XX hermaphrodite that first produces sperm, then oocytes, and an XO male.
      The primary determinant of sex is the X:A ratio, the number of X chromosomes to
      sets of autosomes. The X:A ratio regulates not only sex determination, but also
      dosage compensation. In the intervening years since the identification of the X:A
      ratio, most of the key regulatory genes that respond to the X:A ratio have been
      genetically identified and ordered into regulatory hierarchies. Advances have
      also been made in identifying the X chromosome numerator elements of the X:A
      ratio. This review highlights the genetic, molecular, and biochemical approaches
      that have led to an understanding of how these genes interact to control sex
      determination and dosage compensation. The review also discusses the differences
      between the control of sexual cell fate in the soma and germ line of C. elegans
      and addresses the role of germ-line-specific regulation in controlling the sperm
      oocyte decision in the hermaphrodite germ line. Finally, strategies that take
      advantage of the availability of the entire C. elegans genome sequence, which is
      expected to be completed in 1998, are discussed for identifying hitherto
      unidentified genes that may play a role in the control of sexual cell fate.

PMID- 9784975
TI  - Petal and stamen development.
AB  - Analyses of petal and stamen development are beginning to illuminate the
      molecular genetic processes that are required to elaborate these organ types.
      Floral homeotic genes are required to specify certain organ identities, and these
      functions also are required throughout organogenesis. These genes, either
      directly or indirectly, presumably control a wide array of tissue- and cell-type
      specific differentiation processes. At least part of this repertoire seems to
      include the regulation of cell proliferation, coupling the specification of organ
      identity with changes in growth dynamics in different regions of the developing
      flower. Furthermore, cells have an enormous amount of developmental plasticity,
      which means that they have to be able to integrate multiple sources of
      information as they terminally differentiate. Some of the identified inputs
      include the position of the cell in the developing organ, the status of gene
      expression and epigenetic information, and environmental signals. How this
      information is disseminated between cells is largely unknown. Not only do
      individual cells need to respond to this information, but fields of cells must
      coordinate their differentiation to form a functionally complex structure. The
      challenge that is before us is to understand how this plasticity of response is
      regulated to give a reproducible and species-specific pattern of differentiated
      tissues.

PMID- 9784976
TI  - Gonadotropin-induced resumption of oocyte meiosis and meiosis-activating sterols.

PMID- 9784977
TI  - Comparison of MADRS factors in bipolar II depression versus unipolar depression.

PMID- 9784978
TI  - Social adjustment and the course of affective illness: a one-year controlled
      longitudinal study involving bipolar and unipolar outpatients.
AB  - The association between social adjustment and recurrent affective episodes was
      examined in 27 recovered bipolar patients and 24 recovered unipolar patients who
      had been receiving maintenance treatment for at least 1 year. Social adjustment
      variables and psychiatric status were assessed by bimonthly interviews over the 1
      year period using the Social Adjustment Scale (SAS) and the Research Diagnostic
      Criteria (RDC). Variations in the social adjustment scores were analyzed in the 2
      months preceding the onset of a recurrent affective episode. Furthermore, social
      adjustment variables at entry into the study were assessed to investigate whether
      there was any association between these and the potential timing of a recurrent
      episode. Results revealed no significant deterioration in social adjustment
      during the 2 months preceding a recurrent affective episode. However, it was
      demonstrated that there was a relationship between a patient's overall social
      adjustment score at entry into the study and the onset of recurrent affective
      episodes, independent of any residual depressive symptomatology. Specifically,
      impaired work adjustment in bipolar and unipolar patients was associated with
      recurrent episodes. Impaired social and leisure activities adjustment in bipolar
      patients was also associated with recurrent episodes, and impaired marital
      adjustment in unipolar patients was associated with recurrent episodes. These
      results suggest that social maladjustment could be a risk factor for both
      unipolar and bipolar recurrent affective episodes and that impairment in specific
      areas of social functioning could be used to predict outcome.

PMID- 9784980
TI  - Parental Bonding Instrument and the Inventory to Diagnose Depression Lifetime
      version in a volunteer sample of Japanese workers.
AB  - This study replicated the factor structure of the Parental Bonding Instrument
      (PBI), and explored the relationships of PBI scores to demographic variables. We
      investigated the association between parental bonding in the parents measured by
      the PBI, and lifetime history of depression in their children assessed by the
      Inventory to Diagnose Depression Lifetime version (IDDL) in a volunteer sample of
      239 Japanese workers. In factor analyses with varimax rotation (two-factor
      solution), the PBI items for both parents showed clear bimodality, and the total
      variance explained by the two factors was similar to that found in previous
      Western studies. Subjects with a lifetime history of depression reported a
      significantly lower score on maternal care than did those without a lifetime
      history of depression. Without requiring 2 weeks symptom duration on the IDDL,
      low maternal care was also related to a history of depression. The relationships
      between PBI scores and age, education, sex of respondent, and sex of parent
      differed in part from those in Western subjects. These results suggested the
      following: (1) child-rearing behaviors in non-Western cultures can be, similarly
      to those in Western cultures, described with the PBI; (2) parental styles, as
      measured by the PBI, may be associated with depression in non-Western subjects;
      and (3) sociodemographic influences on PBI scores may be different in subjects
      with different cultural backgrounds.

PMID- 9784979
TI  - EEG sleep in African-American patients with major depression: a historical case
      control study.
AB  - This study was designed to evaluate the effect of race, specifically African
      American, on electroencephalographic (EEG) sleep and clinical symptom profile in
      unipolar major depression. A clinical research database was used to identify
      appropriate subjects and a double-matched historical case-control design was
      implemented. African-American depression patients were double matched within
      protocol to Euro-American depressed patients. Age, sex, and protocol of origin
      were matching variables. African-American depressed patients had less total
      sleep, less slow wave sleep, more stage 2 sleep, longer rapid eye movement (REM)
      sleep latency, less REM sleep, and lower REM density than Euro-American depressed
      patients. African-American depressed patients did not differ from Euro-American
      patients in symptom severity, age of onset, number of episodes, socio-economic
      status, and, as planned, did not differ in age and sex distribution. Depressive
      symptom constellation also did not distinguish the two groups. African-American
      depressed patients demonstrated differences in EEG sleep profile, with less total
      sleep, overall lighter nonREM sleep, and relatively preserved REM sleep, despite
      a clinical symptom profile that did not differ from Euro-American depressed
      patients. The sleep profile appeared to be consonant with the sleep findings in
      chronic insomnia. The pathological implications of these differences remained to
      be explored in careful prospective studies of African-American depressed patients
      and in well-characterized, racially matched normal control comparisons.

PMID- 9784982
TI  - Analysis of depressive symptomatology in mood disorders.
AB  - Depressive disorder is a polymorphic syndrome with a wide range of clinical
      manifestations. Most analyses of depressive symptomatology have been performed by
      ignoring psychotic symptoms, despite a substantial proportion of depressives
      presenting psychotic features. The purpose of this study was to include psychotic
      features in an analysis of depressive symptomatology. Six hundred sixty-nine
      inpatients affected by major depressive (n = 259) and bipolar (n = 410) disorder
      were rated for lifetime depressive symptoms using the Operational Criteria
      checklist for psychotic illness (OPCRIT) and included in a factorial analysis.
      Three factors were obtained: the first consisted of core depressive symptoms, the
      second comprised psychotic features, and the third comprised atypical symptoms.
      Separate analyses performed on major depressive and bipolar samples showed a
      similar factor structure, though there was some evidence of greater heterogeneity
      in the major depressive sample. Thus, when scored by the OPCRIT checklist,
      depressive symptomatology results were composed of core depressive symptoms,
      psychotic features, and atypical symptoms.

PMID- 9784981
TI  - Cerebrospinal fluid concentrations of corticotropin-releasing hormone,
      vasopressin, and somatostatin in depressed patients and healthy controls:
      response to amitriptyline treatment.
AB  - The effect of amitriptyline upon hypothalamic-pituitary-adrenal [HPA]-system
      regulating neuropeptides (corticotropin-releasing hormone [CRH], vasopressin,
      somatostatin) was studied in a group of depressed elderly patients and controls.
      A first lumbar puncture was performed in 37 depressed in-patients. This was
      followed by a 6-week medication phase with amitriptyline. Upon its completion a
      second cerebrospinal fluid (CSF) sample was obtained in 18 of these 37 patients.
      In 25 healthy controls a first lumbar puncture was done eleven of these
      individuals agreed to take 75 mg/d amitriptyline for 6 weeks and to participate
      in the follow-up CSF study. Within the group of depressed patients amitriptyline
      led to a significant decrease of CSF CRH in treatment responders only (F1, 16 =
      5.2; P < 0.02). Also, in normal controls CSF CRH concentration tended to decrease
      with amitriptyline treatment (t-test; P < 0.09). No effects of amitriptyline upon
      vasopressin or somatostatin were observed. In normal controls (r = 0.4; P < 0.02)
      and in patients (r = 0.4; P < 0.03) age correlated positively with baseline CSF
      somatostatin. A trend for CSF CRH to increase with aging was found only in
      controls (r = 0.3; P < 0.09); patients did not show a significant association
      here. Finally, CSF neuropeptide concentration at baseline did not differ between
      the group of depressed patients and healthy controls. Our study corroborates the
      evolving concept that antidepressants effect various components of the HPA system
      with the net result of a reduction in its activity. In addition, we found CSF CRH
      and CSF somatostatin concentrations to be better reflections of age than of
      depression and, finally, that during aging and during depression the HPA system
      changes in similar directions.

PMID- 9784983
TI  - Pap litigation: where do we go from here?

PMID- 9784984
TI  - Cytopathology and AgNOR counts in fine-needle aspiration cytology smears of
      thyroid lesions.
AB  - The object of the present work is to study the cytomorphological features and the
      value of silver colloidal staining method in distinguishing the non-neoplastic,
      benign, and malignant neoplasm in fine-needle aspiration cytology (FNAC) smears
      of thyroid nodules. One hundred forty histologically confirmed aspirated samples
      of thyroid lesions were studied and classified cytologically. These smears were
      stained for AgNOR counts. The number and location of AgNOR dots as well as
      clusters in nuclei were studied by two different observers independently. Lower
      AgNOR counts were recorded in cases of thyroiditis (1.375 +/- 0.414), whereas
      follicular carcinoma had a higher number of AgNOR counts (5.04 +/- 0.52). The
      clusters of AgNOR dots were centrally located in colloid goitre, but no cluster
      arrangement was observed in cases of carcinomas. Increased nuclear size,
      nucleoli, and chromocentres were helpful in the diagnosis of follicular
      carcinoma. AgNOR counting cannot be reliably used on an individual case basis to
      differentiate adenoma from carcinoma. Therefore, AgNOR study in thyroid lesions
      can be used as an additional diagnostic method with cytomorphological features to
      differentiate benign and malignant follicular neoplasms.

PMID- 9784985
TI  - Salivary carcinomas with papillae: cytology and histology analysis of
      polymorphous low-grade adenocarcinoma and papillary cystadenocarcinoma.
AB  - We retrospectively compared fine-needle samplings (FNS) from two recently
      individualized low-grade papillary salivary carcinomas, polymorphous low-grade
      adenocarcinoma (PLGAC) and papillary cystadenocarcinoma (PCAC), to define the
      cytologic criteria allowing the correct diagnosis. Twelve PLGACs in 10 patients
      and 5 PCACs in 4 patients were investigated by FNS preoperatively. In both
      entities, smears contained variable proportions of malignant cells, occasionally
      arranged in pseudopapillary formations. In contrast to PCAC, PLGAC showed stromal
      fragments and hyaline globules resembling pleomorphic adenoma or adenoid cystic
      carcinoma. Cytologic diagnoses of malignancy were established in 10 (83.3%)
      PLGACs and in 4 (80%) PCACs. Two (16.7%) PLGACs were misdiagnosed as pleomorphic
      adenoma, and 1 (20%) PCAC as a salivary cyst.

PMID- 9784986
TI  - Not by blood alone: diagnosis of hemangiomas by fine-needle aspiration.
AB  - Hemangiomas are common vascular neoplasms which are being radiographically
      detected and biopsied with increasing frequency during the workup of patients
      with malignant disease. The increasing confidence of radiologists in biopsying
      these lesions is in contrast to the reluctance of pathologists to make a specific
      diagnosis of hemangioma. Eleven cases of hemangioma, from both hepatic and
      superficial sites, were reviewed and the fine-needle aspirate findings discussed
      and illustrated. Three-dimensional arcades composed of bland elongated spindle
      cells or compact dense coils of spindle cells associated with scattered spindle
      shaped cells were identified in 10 of 11 cases. In conclusion, recognition of the
      cellular pattern of hemangiomas combined with the radiologic information can
      enable a positive diagnosis of hemangioma to be made.

PMID- 9784987
TI  - p53 and bcl-2 protein expression in non-small-cell lung carcinoma.
AB  - The diagnostic significance of p53 and bcl-2 proteins in epithelial non-small
      cell lung cancers was examined, and the relationship between these proteins
      expression and other disease parameters, including stage of the disease and tumor
      differentiation, were studied. We analyzed p53 and bcl-2 proteins expression in
      60 imprint smears of freshly resected lung tumors (37 squamous and 23
      adenocarcinomas) using the immunocytochemical technique. There were seven
      patients with stage I disease, 24 with stage II, 23 with stage IIIa, and six with
      stage IIIb disease, according to the International Staging System classification.
      Sixteen of the tumors were bcl-2 positive and 25 were p53 positive. Twenty tumors
      were negative for both bcl-2 and p53 (33.3%). Statistical analysis showed no
      association between the incidence of p53 or bcl-2 positivity. Adenocarcinoma or
      squamous carcinoma analysis showed significant associations between p53
      positivity and poor differentiation and advanced disease stage as well as bcl-2
      and early disease stage and well-differentiated tumors. There was also an
      association between the stage of the disease and the degree of differentiation of
      the tumors. In conclusion, bcl-2 positivity must be considered a good prognostic
      sign. On the other hand, p53 positivity seems to indicate, even in tumors at a
      relatively early stage, that a serious aggressive tumor which will not be easily
      eradicated is present.

PMID- 9784988
TI  - Fine-needle aspiration cytology of extranodal lymphoma.
AB  - The assessment of lymphoproliferative disorders using fine-needle aspiration
      (FNA) cytology may be problematic particularly when organs other than lymph node
      are involved. In this report we have reviewed 26 consecutive FNA specimens from
      superficial extranodal sites which were reported as diagnostic or suggestive of
      malignant lymphoma. The aspirates were obtained from skin or subcutaneous tissue
      (ten cases), thyroid (five cases), salivary gland (five cases), breast (four
      cases), neck, and pharynx (one case each). Ancillary studies including
      immunocytochemistry, in situ hybridisation to detect immunoglobulin light chain
      mRNA expression, and polymerase chain reaction for analysis of immunoglobulin
      heavy chain gene rearrangement were performed in 20, 12, and 7 cases,
      respectively. Clinicopathologic correlation confirmed the diagnosis of lymphoma
      in 25/26 aspirates. Nine of the 14 patients whose initial presentation was with
      an extranodal mass were considered to have primary lymphomas of mucosa-associated
      lymphoid tissue (MALT) type. In contrast, ten of 11 patients with recurrent
      extranodal disease had primary nodal type lymphomas. There was one false-positive
      diagnosis, a neck mass misinterpreted cytologically as B-cell lymphoma which was
      ultimately shown to be a branchial cyst. FNA cytology supported by appropriate
      ancillary investigations provides accurate diagnosis in most cases of extranodal
      lymphoma.

PMID- 9784989
TI  - Malignant cutaneous and subcutaneous abdominal wall lesions: a fine-needle
      aspiration study.
AB  - Cutaneous and subcutaneous masses of the abdominal wall are uncommon. However, a
      variety of benign and neoplastic entities can be encountered in this region. We
      report a series of 22 fine-needle aspirations (FNA) of malignant cutaneous and
      subcutaneous lesions involving the abdominal wall. All of these lesions were
      metastatic neoplasms. There were 14 females and eight males, with an age range of
      35-83 years (mean 65 years). Twenty-one had a previous history of malignancy. The
      mean interval between the primary diagnosis and FNA was 26 months (range 1.5-128
      months). The sites of origin in order of decreasing frequency were colon (n = 4),
      ovary (n = 4), breast (n = 3), endometrium (n = 2), melanoma (n = 2), and one
      case each of cervix, urinary bladder, kidney, pancreas, gallbladder, and
      lymphoma. One case was a squamous-cell carcinoma of unknown origin. Fourteen of
      the 22 patients were dead at the end of this study, with a mean survival of 8.4
      months (range 0.5-44 months) following FNA. One patient was alive with disease at
      13 months, and seven patients were lost to follow-up. Based on this data and on
      review of the literature we conclude that the majority of malignant cutaneous and
      subcutaneous lesions of the abdominal wall subject to FNA biopsy are metastatic
      tumors which originate from intra-abdominal, pelvic, and retroperitoneal organs
      and that FNA is a highly useful technique in the assessment of these lesions of
      the abdominal wall.

PMID- 9784990
TI  - Cytologic distinction between bronchioalveolar carcinoma and reactive/reparative
      respiratory epithelium: a cytomorphometric analysis.
AB  - Cytologically, the distinction between bronchioalveolar carcinoma and
      reactive/reparative processes of respiratory epithelium can be difficult.
      Retrospectively, we have identified 11 consecutive cases of bronchioalveolar
      carcinoma from the cytology files of University Missouri-Kansas City/Truman
      Medical Center. On average, a combined 5.71 cytologic/histologic procedures were
      performed before reaching a definitive diagnosis for this group. An additional
      seven random cases of reactive/reparative respiratory cases of adult respiratory
      distress syndrome patients were used as a control. Cytomorphometric analysis was
      performed. The mean average nuclear diameter for the carcinoma group was 13.76
      microns and for the reactive/reparative group was 13.29 microns. There was no
      statistical difference between the two groups (paired student t test, P > .05).
      It appears from our data that mean nuclear diameter is not a discriminator for
      the cytologic distinction between bronchioalveolar carcinoma and
      reactive/reparative respiratory epithelium and that the accepted cytologic
      parameters of for bronchioalveolar carcinoma are more valid.

PMID- 9784991
TI  - Flow-cytometric algorithm on fine-needle aspirates for the clinical workup of
      patients with lymphadenopathy.
AB  - To analyze the value and limitations of flow cytometry (FCM) in the investigation
      of patients with lymphadenopathy, a retrospective study of 196 patients, referred
      for fine-needle aspiration (FNA) cytology, was carried out in Canberra,
      Australian Capital Territory, Australia, between 1992-1997. Complete cytological,
      flow-cytometric, and outcome (clinical and histological) data were available on
      all the cases. The FNA appearances were read in conjunction with FCM findings.
      The following cytological categories were recognized: benign, 78 cases (39.8%);
      indeterminate, 9 cases (4.6%); and malignant, 109 cases (55.6%). None of the 78
      cytologically benign cases had malignant outcome. All 109 cytologically malignant
      cases had malignant histology, and 8/9 of the cytologically indeterminate FNAs
      had malignant histology. The cytologically malignant category contained 106 B
      cell lymphomas and three T-cell lymphomas. All 65 B-cell lymphomas with K light
      chain predominance had K/L ratio greater than 3/1, and all 34 B-cell lymphomas
      with L light chain predominance had an L/K ratio greater than 2/1. Clonality was
      therefore established for K/L and L/K at 3/1 and 2/1, respectively. When K/L and
      L/K ratios were below these figures (7 cases), other parameters, including the
      proportion of CD20 and the dual expression of CD19/CD10 and CD20/CD5, were used
      to determine the nature of the aspirate. In the B-cell lymphomas without
      demonstrable light chain restriction, CD20 positivity in excess of 85%, CD19/CD10
      positivity of more than 18%, or CD20/CD5 positivity greater than 35% were
      independently diagnostic of B-cell lymphoma. In the T-cell lymphomas, greater
      than 90% of the cells were T cells, and aberrant T-cell antigen expression with
      loss of at least one pan-T-cell antigen was detected. In conclusion, the
      sensitivity of diagnosis of malignancy, false-negative rate, and predictive value
      of malignant diagnosis with combined FNA cytology and FCM were 99%, 0%, and 100%,
      respectively.

PMID- 9784992
TI  - Accuracy comparison between PAPNET diagnoses and conventional diagnoses in an
      Italian cervical cytology laboratory.
AB  - In a population-based cervical screening laboratory with a controlled workload, a
      retrospective PAPNET review of 1,654 Pap smears was performed. The series
      included a random sample of smears originally and conventionally classified as
      negative (no. 1,309) and unsatisfactory (no. 43), and 299 consecutive smears
      originally classified as abnormal. The PAPNET diagnoses and the original
      diagnoses were compared for accuracy. For smears with discordant classification,
      a majority diagnosis as obtained on manual review was used as a gold standard.
      The PAPNET testing showed a greater proportion of negative smears classified as
      unsatisfactory (3.7% vs. 0.2%; ratio, 16.7; 95% CI 12.4-22.0); a reduced
      proportion of ASCUS/LGSIL cases correctly identified as positive (i.e., a reduced
      sensitivity for such lesions) (76.3% vs. 97.9%; ratio, 0.78; 95% CI 0.66-0.91);
      an equal proportion (96.2%) of AGUS/HGSIL cases correctly identified as positive
      (i.e., an equal sensitivity for such lesions); and an equal proportion of
      negative smears correctly identified as such (i.e., an equal specificity). In
      conclusion, the PAPNET testing did not improve the diagnostic performance of the
      manual screening.

PMID- 9784993
TI  - Endometrial intraepithelial carcinoma diagnosed by brush cytology and p53
      immunostaining, and confirmed by hysterectomy.
AB  - Endometrial intraepithelial carcinoma (EIC) is associated with tumors of high
      nuclear grade and usually is seen in endometria without complex atypical
      hyperplasia. Tumor cells oftentimes show an accumulation of mutant p53 protein.
      This report describes a case of EIC detected by endometrial brush cytology and
      p53 immunostaining, and confirmed by hysterectomy.

PMID- 9784994
TI  - Calcified mitochondria in epithelial cells of the respiratory tract in upper
      respiratory thermal injury.
AB  - Multiple hematoxyphilic small granules were found in the respiratory columnar
      cells in smears from bronchial washings in a symptomatic boy who had suffered
      from extensive burns in his face and was suspected to had developed thermal
      injury of the upper respiratory tract. These granules proved to be immunoreactive
      for mitochondria antigen antibodies and to contain calcium salts after the von
      Kossa stain. Calcified mitochondria may represent a peculiar phenotype of thermal
      injury to the bronchial lining cells.

PMID- 9784995
TI  - Fine-needle aspiration diagnosis of foreign body granulomatous reaction
      presenting as an orbital mass: case report and review of the literature.
AB  - Foreign body granuloma is a rare cause for an orbital mass. A case with proptosis
      and an orbital mass on CT scan is presented. Fine-needle aspiration of the mass
      was performed. Numerous foreign body giant cells were seen which contained
      polarizable filamentous material. A diagnosis of foreign body granuloma was
      rendered which was confirmed on histopathology.

PMID- 9784996
TI  - Metastatic granulosa-cell tumor in the liver: cytopathologic findings and
      staining with inhibin.
AB  - Adult granulosa-cell tumor (AGCT) is an uncommon ovarian malignancy. Rarely,
      hepatic metastasis of this tumor may present a difficult cytologic diagnosis when
      such a lesion is aspirated. This case report elaborates the cytopathologic
      features of AGCT in the liver aspirate of a 60-yr-old woman. Correlation with
      histopathology and intraoperative touch-imprint cytology of the subsequent
      hepatic resection is also presented. The role of immunoperoxidase studies
      especially utilizing inhibin is also highlighted.

PMID- 9784997
TI  - Psammomatous melanotic schwannoma localized in the mediastinum: diagnosis by fine
      needle aspiration cytology.
AB  - The cytological characteristics are presented in a case of psammomatous melanotic
      schwannoma localized in the mediastinum, diagnosed by fine-needle aspiration
      cytology (FNAC), with later histological confirmation. This lesion affected a 38
      year-old male, with a tumor measuring 5 cm in diameter located in the posterior
      mediastinum in contact with the spinal cord, with erosion of the adjacent
      vertebra (T5), that caused constant pain localized in the right scapular region
      with an evolution of several weeks. The cytological characteristics of
      psammomatous melanotic schwannoma are discussed, along with the histological and
      immunohistochemical features of this infrequent neural tumor, which aid in
      establishing a differential diagnosis. The importance of a correct histological
      diagnosis of this tumor is of particular clinical relevance after having been
      identified as one of the possible components of Carney's complex. This
      possibility demands a meticulous patient exploration in search of any other
      components that make up this complex, given the aggressive character of some of
      them. These lesions could, if not detected early enough, produce fatal
      consequences for the patient, fundamentally in those patients with cardiac
      myxomas. In this case, following an exhaustive clinical examination there was no
      pathology associated with this complex. It is therefore considered to be an
      isolated psammomatous melanotic schwannoma, and not a part of Carney's complex.

PMID- 9784998
TI  - Pleuropulmonary blastoma: diagnosis by fine-needle aspiration cytology: a case
      report.
AB  - Pleuropulmonary blastoma (PPB) is an unusual pleural-based blastoma presenting in
      childhood composed by undifferentiated sarcomatous tissue with divergent
      differentiation and occasional benign epithelial-lined structures. We are
      presenting the cytologic features of PPB as diagnosed by fine-needle aspiration
      cytology (FNAC) of the lower lobe of the right lung in a 4-year-old girl. The
      smears showed highly malignant cells with hyperchromatic oval or multilobulated
      pleomorphic nuclei strongly suggesting an aggressive sarcoma. Histology of the
      aspirated material also revealed small fragments of a myxoid sarcoma with some
      pleomorphic anaplastic cells. Lobectomy and surgical pathologic investigation
      confirmed the diagnosis. PPB seems to be another tumor in which accurate
      diagnosis may be achieved by FNAC.

PMID- 9784999
TI  - Mixed hepatoblastoma diagnosed by fine-needle aspiration biopsy cytology: a case
      report.
AB  - The cytologic features of a case of mixed hepatoblastoma diagnosed by fine-needle
      aspiration biopsy (FNAB) in a 2 1/2-yr-old child are described. FNAB was carried
      out on a large, firm mass in the upper abdomen, without any complications. The
      characteristic cytologic features were clusters of polyhedral cells with mild
      anisonucleosis, and intracytoplasmic bile pigment. Focal areas of mesenchymal
      elements were seen. Immature hematopoietic cells were present. FNAB offers a safe
      and accurate method of diagnosis.

PMID- 9785000
TI  - Presence of nuclear grooves in the cytology of malignant melanoma.
AB  - Nuclear grooves have been described as a cytologic feature in a variety of
      extrathyroid lesions. When a cytologic specimen demonstrates prominent
      longitudinal nuclear grooving, a wide range of pathologic lesions should be
      considered. To our knowledge, the two cases presented are the first report of
      longitudinal nuclear grooving described in cytologic preparations of malignant
      melanoma.

PMID- 9785001
TI  - Cytologic detection of Trichomonas esophagitis in a patient with acquired
      immunodeficiency syndrome.
AB  - Trichomonads are pathogens of the female genital tract and colonizers of the
      oropharynx. Gastrointestinal and pulmonary diseases have been reported in
      association with Trichomonas species, but a direct pathogenic effect of this
      organism in these organ systems remains controversial. Esophageal disease due to
      trichomonads has not been previously reported. A 43-yr-old man with acquired
      immunodeficiency syndrome (AIDS) with odynophagia and esophageal erosions was
      evaluated by endoscopy. Cytologic brushings from three of four sites in the
      esophagus were positive for trichomonads. Treatment with metronidazole resulted
      in clearance of the organism from the esophagus and improvement in clinical
      symptoms. We report esophageal trichomoniasis diagnosed on esophageal brush
      cytology in a man with AIDS. Clinical response was confirmed by cytologic studies
      and odynophagia improved with metronidazole treatment. Study of cytologic
      preparations was superior to biopsy for identification of this organism and was
      particularly useful in following the post-treatment course of disease.

PMID- 9785002
TI  - Reporting fine-needle aspirates of breast: a survey of preferences among
      surgeons.
AB  - BACKGROUND: The optimal format for reporting results of breast fine-needle
      aspiration cytology is controversial, with some experts favoring a five-category
      system and others recommending a four-category format. METHODS: A survey of 200
      surgeons was performed to determine their preference for a four- or five-category
      report format. They were also questioned concerning the number of patients per
      year in whom they diagnosed breast cancer, if they used fine-needle aspiration
      cytology (FNAC) regularly, and why they favored one category over the other.
      RESULTS: Eighty-five complete responses were received. Fifty-eight percent of
      these surgeons (49) routinely used FNAC for the diagnosis of breast nodules.
      There was no strong preference for either report format. Twenty-four of 49
      routine users of FNAC favored a four-category format, and another four had no
      preference. CONCLUSION: Surgeons who routinely used FNAC in the diagnosis of
      breast disease do not have a preference for the five-category probabilistic
      system.

PMID- 9785003
TI  - Pathogenesis of autosomal dominant polycystic kidney disease: role of apoptosis.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenic
      disorder with progressive distension of multiple tubular segments, and is
      manifested by fluid accumulation, growth of epithelial cells, and remodeling of
      the extracellular matrix, ultimately resulting in renal insufficiency in one half
      of affected individuals. The process causing the progressive loss of renal tissue
      is unclear. Recent studies demonstrate that apoptosis is one of the major
      histopathologic features of ADPKD and may be causally related to the progressive
      deterioration of the renal function in this population. Further studies are
      required to elucidate the mechanisms by which some cysts upregulate the process
      of programmed cell death in the kidney.

PMID- 9785004
TI  - Automated in situ hybridization: diagnostic and research applications.
AB  - Although in situ hybridization has been in use for almost 30 years, its
      technically demanding nature, the requirements for optimal tissue fixation and
      preservation, and the turnaround time for the experiments have prevented this
      technique from becoming widely used in the surgical pathology setting. The use of
      nonisotopic reporter molecules, the possibility of performing hybridization on
      archival material, and very recently, automation of the procedure have brought in
      situ hybridization to the forefront of diagnostic and experimental pathology. We
      describe our experience with nonradioactive, automated in situ hybridization,
      compare the technique with traditional manual procedures, and briefly outline its
      potential applications in diagnostic pathology and in the research setting.

PMID- 9785005
TI  - In situ hybridization detection of low copy nucleic acid sequences using
      catalyzed reporter deposition and its usefulness in clinical human papillomavirus
      typing.
AB  - In situ hybridization (ISH) detection of low copy DNA and RNA sequences using
      nonisotopic probes has been difficult in the past because of a lack of
      sensitivity. Several techniques, such as ISH with radioisotopic-labeled probes,
      in situ polymerase chain reaction, in situ reverse transcription polymerase chain
      reaction, self-sustained sequence replication, and chemiluminescence, have
      allowed increased sensitivity but have required specialized and often expensive
      equipment, lengthy protocols, and in the case of radioactive probes, there has
      been an associated increased health risk. Catalyzed reporter deposition (CARD)
      combined with ISH (CARD-ISH) increases the signal-generating potential of labeled
      hybridized probes and allows the detection of low copy sequences of nucleic acids
      in formalin-fixed, paraffin-embedded tissue sections. To determine the
      sensitivity of CARD-ISH to detect nucleic acids in routinely processed specimens,
      we analyzed the detection of HPV 16 and 18 infection in formalin-fixed, paraffin
      embedded sections of cultured cell lines, including CaSki cells with 400-600
      copies of HPV 16, HeLa 229 cells with 10-50 copies of HPV 18, and SiHa cells with
      1-2 copies of HPV 16 using a conventional ISH method and by CARD-ISH. In
      addition, 20 cases of clinical specimens previously analyzed for HPV 6, 11, 16,
      18, 31, 33, and 51 with the Enzo PathoGene kit (Enzo Diagnostics, Inc.,
      Farmingdale, NY, U.S.A.) were reexamined with the CARD-ISH method. The CARD-ISH
      system detected one to two copies of HPV 16 in the SiHa cells whereas the
      conventional ISH method did not. Both methods detected HPV 16 and 18 in CaSki and
      HeLa 229 cells, respectively. Three clinical cases that were previously negative
      and two weakly positive cases of HPV infection were all strongly positive with
      the CARD-ISH system, a 25% increase in the detection of positive cases by CARD
      ISH. We also showed for the first time that a cocktail of six biotinylated
      oligonucleotide probes was capable of detecting one to two copies of HPV 16 in
      SiHa cells. These results show that the CARD-ISH method increases the sensitivity
      of nonisotopic ISH to the level of detecting one to two copies of HPV DNA in
      formalin-fixed, paraffin-embedded tissue sections using biotinylated cDNA or
      oligonucleotide probes.

PMID- 9785006
TI  - Novel bcl-2 breakpoints in patients with follicular lymphoma.
AB  - Using genomic DNA from patients with follicular lymphoma, we performed polymerase
      chain reaction (PCR) amplifications to detect t(14;18) translocations.
      Unexpectedly large products of approximately 1 kilobase (kb) were detected by gel
      electrophoresis in 2 of 50 positive cases. In these 2 cases, sequence analyses
      showed novel breakpoints in the 3' untranslated region of bcl-2, approximately
      800 bp downstream of the major breakpoint region (mbr). The breakpoints in IgH
      occurred in JH4 in one patient and JH5 in the other. Sequences just upstream of
      the new bcl-2 breakpoints suggest a mechanism of translocation that may include
      minisatellite core-mediated recombination. In one of our two patients with novel
      bcl-2 breakpoints, the approximately 1 kb product obtained using conventional mbr
      primers was detectable only when a nested PCR was performed. These findings have
      important implications for diagnosis and minimal residual disease detection in
      t(14;18)-positive lymphomas.

PMID- 9785007
TI  - Morphologic, immunophenotypic, and molecular evaluation of bone marrow
      involvement in non-Hodgkin's lymphoma.
AB  - The diagnosis of marrow involvement in non-Hodgkin's lymphoma (NHL) relies on
      morphology with support from immunophenotyping by flow cytometry (FCM). We
      assessed the relative sensitivity of morphology, FCM, and consensus primer
      polymerase chain reaction (PCR) of antigen receptor genes in the detection of
      marrow involvement. In 78 of 100 (78%) cases, there was concordance between FCM
      and PCR. FCM detected more cases of clonality in B-cell neoplasia. There were 40
      cases with objective evidence of involvement by B-cell neoplasia. In this group,
      FCM had a sensitivity of 97.5% (39 of 40); PCR had a sensitivity of 67.5% (27 of
      40). In contrast, PCR had a sensitivity of 71.4%, and FCM a sensitivity of 28.6%,
      in T-cell neoplasia. In all 12 cases with involvement detected by biopsy, there
      was objective evidence of clonality. However, clonality was detected in four of
      seven patients with chronic lymphocytic leukemia and in five of eight patients
      with T-cell neoplasia in the absence of morphologically detectable disease.
      Clonality was identified in only one of seven patients with B-cell lymphoma in
      which the biopsy was interpreted as "suspicious but not diagnostic of
      involvement." We conclude that morphology remains of central importance in the
      evaluation of marrow involvement in NHL. We show that FCM and PCR identify
      involvement in the absence of morphologically apparent disease. In B-cell
      neoplasms, FCM remains the method of choice for the detection of clonality. PCR
      for T-cell receptor gene rearrangements may be an important adjunct to the
      diagnosis of marrow involvement in patients with T-cell neoplasms.

PMID- 9785008
TI  - Detection of TLS/FUS-CHOP fusion transcripts in myxoid and round cell
      liposarcomas by nested reverse transcription-polymerase chain reaction using
      archival paraffin-embedded tissues.
AB  - The reciprocal translocation t(12;16)(q13;p11) has been shown to be highly
      characteristic of myxoid and round cell subtypes of liposarcoma, and the TLS/FUS
      CHOP fusion gene that resulted from the translocation is expected to be a
      diagnostic molecular marker of these sarcomas. In this study, we conducted a
      nested reverse transcription-polymerase chain reaction (RT-PCR)-based assay to
      detect the TLS/FUS-CHOP fusion gene transcripts using archival formalin-fixed,
      paraffin-embedded tumor specimens. Of 18 paraffin-embedded specimens from 16
      myxoid and round cell liposarcoma cases, the fusion transcripts could be
      identified in 16 (89%) specimens from 15 (94%) cases. A sequence analysis using
      the PCR products confirmed that the detected messages were derived from either
      type I or type II TLS/FUS-CHOP fusion gene, the latter of which was predominant
      (80%). The results were consistent in primary and recurrent lesions of the same
      patients and in paraffin-embedded and snap-frozen samples from the same tumors.
      In two negative specimens, transcripts of the beta-actin gene could not be
      detected by RT-PCR, and intact mRNA including the fusion messages might have been
      degraded. No fusion transcripts were detected in snap-frozen or paraffin-embedded
      material of other types of tumors with myxoid morphology (seven myxoid malignant
      fibrous histiocytomas and four lipomas with myxoid change). These results
      indicate that this molecular assay can be applied to formalin-fixed, paraffin
      embedded tumor tissues as a diagnostic aid for these subtypes of liposarcoma.

PMID- 9785009
TI  - Diagnosis of synovial sarcoma with the reverse transcriptase-polymerase chain
      reaction: analyses of 84 soft tissue and bone tumors.
AB  - The chimeric transcript SYT-SSX is generated as a result of reciprocal
      translocation t(X;18), which is the primary cytogenetic abnormality found in, and
      appears to be specific for, synovial sarcoma. We performed a reverse
      transcriptase-polymerase chain reaction (RT-PCR) for SYT-SSX transcripts in a
      series of 84 tumors (61 soft tissue tumors and 23 bone tumors), including a
      variety of histologic types, to assess its usefulness in molecular diagnosis. Ten
      synovial sarcomas, three tumors initially unclassified, and one malignant
      peripheral nerve sheath tumor contained the chimeric transcripts. A review of the
      original slides and additional examination showed that a diagnosis of synovial
      sarcoma was appropriate for these cases. Additionally, in situ hybridization with
      an SSX1 probe indicated that the chimeric transcripts exist not only in the cells
      of special components but also in cells showing a variety of histologic patterns.
      Therefore, RT-PCR can be considered a useful molecular biological technique that
      can provide objective evidence for diagnosis of synovial sarcoma. Northern blot
      analysis with an SSX1 probe also detected chimeric SYT-SSX transcripts in the
      synovial sarcoma cases. The additional smaller bands, however, were also detected
      in six peripheral primitive neuroectodermal tumors (pPNETs) and one embryonal
      rhabdomyosarcoma. In five of these pPNETs, other bands ranging in size from 2.0
      to 2.2 kb were also found, and it seems possible that these bands might represent
      novel karyotypic aberrations and/or splicing variants of SSX.

PMID- 9785010
TI  - Heteroduplex analysis: a useful screening method for glycogen storage disease
      type Ia.
AB  - Glycogen storage disease type Ia (GSDIa), also known as von Gierke disease, is
      the most common and severe disease of glycogenoses and is caused by a deficiency
      of glucose-6-phosphatase (G6Pase) and transmitted by an autosomal recessive
      trait. The encoding gene of G6Pase is composed of only five exons and each exon
      is short. With heteroduplex analysis (HDA) method, we analyzed the genomic DNA
      from a patient diagnosed with GSDIa and from her parents. Exons II and IV of the
      patient showed heteroduplex bands. The mother had a heteroduplex band of exon II,
      and the father had a heteroduplex band of exon IV. In a mini-slab
      electrophoresis, exons II and IV of the patient did not show clear heteroduplex
      bands, but they appeared broader than the others, which made us suspect that they
      were heteroduplex bands. HDA is an easy and simple method and can verify mutant
      homozygous DNA fragments by adding wild-type DNA. We think that HDA may be a very
      useful screening method for the detection of novel genomic mutation in GSDIa in
      large-scale and mini-slab electrophoresis.

PMID- 9785011
TI  - Discrimination of human papillomavirus types in low and high grade cervical
      squamous neoplasia by in situ hybridization.
AB  - We have previously demonstrated that cross-hybridization between probe and target
      occurs in the analysis of human papillomavirus (HPV) 6 and 11, and HPV 16, 31 and
      33 infection by in situ hybridization (ISH) in archival tissue biopsies. In this
      study, 50 low grade and 50 high grade cervical lesions were analyzed using HPV
      6/11, 16, 18, 31 and 33 probes to determine the typing accuracy of high
      sensitivity ISH for a wide range of HPV types. The sensitivity of both ISH and
      PCR was 92% in low grade lesions and 90% and 96%, respectively, in high grade
      lesions, with an overall concordance of 97%. The typing accuracy of ISH was only
      43% in low grade lesions but 93% in high grade lesions. This was due largely to
      cross-hybridization of the probes used with other HPV types (HPV 39, 42, 43, 44,
      45, 51, 52, 56, 58, and 66). Although analysis of ISH patterns could narrow down
      these other HPV types, precise identification was not possible by this means.
      These data suggest that when high sensitivity ISH methods are used, particularly
      in low grade lesions, HPV typing by ISH should be supplemented by independent
      determination of HPV type by PCR.

PMID- 9785013
TI  - [Identification of baculovirus protein binding preferentially single-stranded DNA
      and melting double-stranded DNA].

PMID- 9785012
TI  - Bowenoid papulosis showing polyclonal nature.
AB  - Bowenoid papulosis (BP) is characterized clinically by its benign-looking
      appearance and histologically by the features of high grade squamous
      intraepithelial lesions (SILs). The external genitalia of young people is a
      common site of occurrence, and most of the lesions undergo resolution by local
      treatments or even spontaneously. A strong association between BP and high risk
      types of human papillomavirus (HPV), especially HPV 16, has been reported and the
      incorporation of BP into the SIL category is generally accepted, but controversy
      still exists as to the true nature of BP. We analyzed the clonality of BP lesions
      occurring on both sides of the vulva of a 15-year-old girl. DNA was subjected to
      a polymerase chain reaction-based clonal analysis using the highly informative
      androgen receptor gene (HUMARA) with a nonisotopic modification. The clonal
      analysis of each BP lesion showed a random X-chromosome inactivation pattern,
      indicating a polyclonal nature of this disorder. Although monoclonal
      proliferation of vulvar SIL was recently reported, this is the first report of
      the polyclonality in a type of SIL diagnosed as BP, supporting a
      clinicopathologic heterogeneity in SIL of the vulva.

PMID- 9785014
TI  - [Position of 19 regions of DNA binding to nuclear matrix (MAR) on human
      chromosome 19].

PMID- 9785015
TI  - [Mechanism of anticholinesterase action of cation-containing organophosphorus
      inhibitors].

PMID- 9785016
TI  - [Para-aminobenzoic acid as an antioxidant].

PMID- 9785018
TI  - [Regulating effect of trihydroxyoctadecadienoic acids from Bryonia alba on
      glucose-fatty acids cycle in alloxan diabetes].

PMID- 9785017
TI  - [Resistance of Na+,K+-ATPase of brain synaptosomes to high environmental pressure
      in vertebrates].

PMID- 9785019
TI  - [Cholesteroyl derivatives of oligoethylenimine as mediators of transfection of
      eukaryotic cells in gene therapy].

PMID- 9785020
TI  - [The effect of o-aminoazotoluene on glucocorticoid induction of tyrosine
      aminotransferase in mice sensitive to its hepatocarcinogenic activity is mediated
      by transcription factor HNF3gamma].

PMID- 9785021
TI  - [Changes in the structure of molecular layer of the Rana temporaria cerebellum
      after exposure to NO-generating compounds. 1. Impairment of integrity of
      membranes of cerebellar parallel fibers and buds and their fusion].

PMID- 9785022
TI  - [Relation between the space flight-induced frequency of dominant lethal mutations
      and the level of allozyme heterozygosity in Drosophila melanogaster populations].

PMID- 9785023
TI  - [Interspecies cross of ixodes ticks from the group Ixodes ricinus-persulcatus].

PMID- 9785024
TI  - [SUP35 gene in Pichia methanolica is a recessive suppressor in Saccharomyces
      cerevisiae].

PMID- 9785025
TI  - [Neonatal administration of ACTH(1-10) causes genotype-dependent changes in the
      level of brain monoamines and audiogenic sensitivity in adult CBA and 101/HY
      mice].

PMID- 9785026
TI  - [A novel approach to the study of topoisomerase I kinetics].

PMID- 9785027
TI  - [Tissue specificity of cyclin B expression in D. melanogaster].

PMID- 9785028
TI  - [Compensation of postradiation and age-related disorders using thymus or bone
      marrow transplantation into immunoprivileged regions].

PMID- 9785029
TI  - [Pulsed activity in the sensory mesenteric nerve fibers after exposure to an
      antigen].

PMID- 9785030
TI  - Neuroimmunoregulation and natural immunity.
AB  - The development and function of the immune system is regulated by neuroendocrine
      factors. Immune function may be divided into adaptive and natural immunity.
      Adaptive immune responses are driven by specific determinants of the antigen
      (epitopes), require 5-10 d to fully develop, and show an accelerated or memory
      response after repeated exposure to the same antigen. Natural immunity may be
      divided into host defense mediated by non-immune factors (e.g., antimicrobial
      proteins, enzymes, mucus etc.) and polyspecific responses of the immune system.
      This polyspecific response relies on natural antibodies and on some other serum
      proteins (e.g., lipopolysaccharide-binding protein-LBP, C-reactive protein-CRP),
      and on surface receptors of macrophages, natural killer cells and B and T
      lymphocytes for activation. Highly conserved homologous (crossreactive) epitopes,
      or homotopes for short, are recognized by the natural immune system. Natural
      antibodies, LBP, and CRP are capable of activating the entire immune system after
      combination with the appropriate homotope. During febrile illness natural immune
      host defense is promptly elevated because of the rapid rise of natural
      antibodies, LBP, and CRP in the serum. This is known as the acute phase response
      (APR), which is initiated by a sudden rise of cytokines in the circulation, such
      as IL-1, IL-6, and TNF-alpha. The cytokines act on the brain, the neuroendocrine
      system, and on other tissues and organs, which leads to fever and profound
      hormonal and metabolic changes. The hypothalamus-pituitary adrenal axis is
      activated and serves as the primary regulator of immune and inflammatory
      reactions. Insulin, glucagon, and catecholeamine levels are also raised. Bone
      marrow activity and leukocyte function are high and the liver is converted to the
      rapid production of acute-phase proteins (APP). APP include LBP, CRP, fibrinogen,
      some complement components, enzyme inhibitors, and anti-inflammatory proteins,
      which may rise in the serum from several hundred to a thousand times within 24-48
      hr. Therefore, natural immunity is a polyspecific response to homotopes, which
      functions as an instantaneous defense mechanism in health and which is rapidly
      boosted by cytokines and hormones during febrile illness. This is a highly
      successful defense reaction, as in the overwhelming majority of cases, febrile
      illness leads to recovery and the development of adaptive immunity in man and
      higher animals.

PMID- 9785031
TI  - Environmental modulation of the immune system via the endocrine system.
AB  - Numerous studies have demonstrated that a variety of hormones have receptors and
      exert biologic actions on tissues of the immune system. Conversely, cytokines
      exert biologic actions on the endocrine system. This bidirectional interaction is
      likely involved in maintenance of physiological and immunologic homeostasis. This
      paper summarizes a variety of actions of growth hormone (GH), prolactin (PRL),
      insulin-like growth factor-I (IGF-I), glucocorticoids and thyroid hormones (TH)
      on the immune system. It then proceeds to put these actions into a hypothetical
      context whereby these hormones may mediate some changes in immune system function
      in response to environmental stimuli such as physical and emotional stress,
      nutritional deprivation and environmental temperature. In the first example, it
      is proposed that PRL secretion in response to stress may serve an
      immunomodulatory role in two ways. The first is by stimulating the immune system
      directly and the second is by dampening or reducing the degree to which
      glucocorticoids are secreted in response to stress. The second example suggests
      that the increase in GH secretion and reduced IGF-I secretion in response to
      protein/energy restriction may have two potential immunomodulatory actions. One
      action is a direct effect of GH on several components of the immune system. The
      other is the partitioning of nutrient use away from skeletal muscle growth and
      toward tissues of higher priority such as the immune system. The third example
      proposes that the increased secretion of TH during cold environmental
      temperatures not only increases basic metabolic rate, but also directly
      stimulates both primary and secondary lymphoid tissues. It is suggested,
      therefore, that these three hormones are involved in maintaining immune system
      homeostasis in response to environmental change.

PMID- 9785032
TI  - A new theory on the common evolutionary origin of natural immunity, inflammation
      and stress response: the invertebrate phagocytic immunocyte as an eye-witness.
AB  - Data in favor of the hypothesis of the common evolutionary origin of natural
      immunity inflammation and stress response are presented. These phenomena seem to
      be mediated by a common pool of molecules (POMC-derived peptides, cytokines,
      biogenic amines, glucocorticoids, and nitric oxide). Macrophages are able to
      release all the above mentioned molecules. They play a primary role in defence
      mechanisms. Thus, we argue that this cell can be considered the eye-witness of
      the common evolutionary origin of the immune and neuroendocrine systems.

PMID- 9785033
TI  - Coordinated host defense through an integration of the neural, immune and
      haemopoietic systems.
AB  - Interactions between the neural and immune systems exist through humoral factors
      operating via the hypothalamic-pituitary-adrenal axis and cytokines acting over a
      relatively long distance. Anatomical evidence also suggests direct, hard-wired
      pathways of interaction and control through innervation of lymphoid organs and
      peripheral sites involved in host defense, including the thymus, spleen, lymph
      nodes, and skin. Recent evidence has demonstrated: 1) neural control of the bone
      marrow haemopoietic system, 2) interactions between peripheral nerve endings in
      the skin and epidermal Langerhans cells, and 3) peripheralization of leukocytes
      in the initial stages of stress. This leads us to propose that the nervous system
      is involved in host monitoring and coordination of host defense systems. If the
      brain is to have appropriate control of host defense mechanisms it must have: (a)
      afferent inputs monitoring host defense status, (b) efferent control pathways
      that modulate primary reactions to infection and damage, (c) efferent activation
      pathways to the myeloid defense system while the specific, lymphoid immune system
      is activated, and (d) inhibition of the proliferative lymphocytic response if the
      infection has been dealt with. We are investigating whether such a model, which
      allows for control and coordination of both the initial myeloid defense system
      and of the acquired immune response, is observed in mammals.

PMID- 9785034
TI  - Endotoxins and endocrine system.
AB  - There is good evidence for the interaction of neuroendocrine and immune systems.
      Endotoxin (LPS)-induced mediators (e.g., cytokines, prostaglandins etc) set on
      endocrine organs (e.g., the hypothalamo-pituitry-adrenal axis; thyroid glands
      etc). Endotoxin-treated, intestinal ischemic, or irradiated rats show decreased
      T4 levels of blood. These animals cannot respond to TSH because the TSH-receptors
      of follicular membranes are disturbed by LPS in the thyroid glands.
      Radiodetoxified endotoxin is an effective immunstimulator and does not disturb
      the follicular membrane of thyroid gland. Thus, the T4 production remains normal.
      The bile acids--as the end-product of cholesterol metabolism--play an important
      role in the physiological defense of macroorganisms against endotoxin and other
      lipid-like agents (Physico-chemical defense) and in the regulation of endocrine
      system, including the reproduction.

PMID- 9785035
TI  - Immune and endocrine regulation of food intake in sick animals.
AB  - To understand why sick animals do not eat, investigators have studied how the
      immune system interacts with the central nervous system (CNS), where motivation
      to eat is ultimately controlled. The focus has been on the cytokines secreted by
      activated mononuclear myeloid cells, which include interleukin-1 beta (IL-1
      beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). Either
      central or peripheral injection of recombinant IL-1 beta, IL-6, and TNF-alpha
      reduce food-motivated behavior and food intake in rodents. Moreover, these
      cytokines and their receptors are present in the endocrine system and brain, and
      antagonism of this system (i.e., the cytokine network) has been shown to block or
      abrogate anorexia induced by inflammatory stimuli. Recent studies indicate that
      the same cytokines act on adipocytes and induce secretion of leptin, a protein
      whose activity has been neuroanatomically mapped to brain areas involved in
      regulating food intake and energy expenditure. Therefore, many findings converge
      to suggest that the reduction of food intake in sick animals is mediated by
      inflammatory cytokines, which convey a message from the immune system to the
      endocrine system and CNS. The nature of this interaction is the focus of this
      short review.

PMID- 9785036
TI  - The anti-gonadotropic effects of cytokines: the role of neuropeptides.
AB  - The inhibitory effect of inflammation and endotoxins on the secretion of
      reproductive hormones from the hypothalamo-pituitary axis is well documented. A
      comparison of the luteinizing hormone (LH) suppressing effects of several pro
      inflammatory cytokines revealed that centrally administered IL-1 beta was the
      most potent inhibitor of pituitary LH secretion; interleukin (IL)-1 alpha and
      tumor necrosis factor (TNF) alpha were relatively less effective, whereas IL-6
      was ineffective. This order of potency suggested that the anti-gonadotropic
      effects of an immune challenge are most likely attributable to the action of
      centrally released IL-1 beta, and this was supported by the demonstration that IL
      1 beta suppressed hypothalamic luteinizing hormone releasing hormone (LHRH)
      release. We used a multifaceted approach to identify the afferent signals in the
      brain that convey immune messages to hypothalamic LHRH neurons. Pharmacological
      studies with specific antagonists of opioid receptor subtypes demonstrated that
      activation of the mu 1 receptor subtype was required to transmit the cytokine
      signal. Furthermore, icv IL-1 beta upregulated hypothalamic POMC mRNA and
      increased the concentration and release of beta-endorphin, the primary ligand of
      mu 1 receptors. We have obtained evidence that IL-1 beta also enhanced the gene
      expression and concentration of tachykinins, a family of nociceptive
      neuropeptides in the hypothalamus. Blockade of tachykinergic NK2 receptors
      attenuated IL-1 beta induced inhibition of LH secretion. Collectively, these
      results demonstrate that IL-1 beta, generated centrally in response to
      inflammation, upregulates the opioid and tachykinin peptides in the hypothalamus.
      These two groups of neuropeptides are critically involved in relaying the
      cytokine signal to neuroendocrine neurons and causing the suppression of
      hypothalamic LHRH and pituitary LH release.

PMID- 9785037
TI  - Hypothalamic control of gonadotropin secretion by LHRH, FSHRF, NO, cytokines, and
      leptin.
AB  - Gonadotropin secretion by the pituitary gland is under the control of luteinizing
      hormone-releasing hormone (LHRH) and the putative follicle stimulating hormone
      releasing factor (FSHRF). Lamprey III LHRH is a potent FSHRF in the rat and seems
      to be resident in the FSH controlling area of the rat hypothalamus. It is an
      analog of mammalian LHRH and may be the long sought FSHRF. Gonadal steroids
      feedback at hypothalamic and pituitary levels to either inhibit or stimulate the
      release of LH and FSH, which is also affected by inhibin and activin secreted by
      the gonads. Important control is exercised by acetylcholine, norepinephrine (NE),
      dopamine, serotonin, melatonin, and glutamic acid (GA). Furthermore, LH and FSH
      also act at the hypothalamic level to alter secretion of gonadotropins. More
      recently, growth factors have been shown to have an important role. Many peptides
      act to inhibit or increase release of LH and the sign of their action is often
      reversed by estrogen. A number of cytokines act at the hypothalamic level to
      suppress acutely the release of LH but not FSH. NE, GA, and oxytocin stimulate
      LHRH release by activation of neural nitric oxide synthase (nNOS). The pathway is
      as follows: oxytocin and/or GA activate NE neurons in the medial basal
      hypothalamus (MBH) that activate NOergic neurons by alpha, (alpha 1) receptors.
      The NO released diffuses into LHRH terminals and induces LHRH release by
      activation of guanylate cyclase (GC) and cyclooxygenase. NO not only controls
      release of LHRH bound for the pituitary, but also that which induces mating by
      actions in the brain stem. An exciting recent development has been the discovery
      of the adipocyte hormone, leptin, a cytokine related to tumor necrosis factor
      (TNF) alpha. In the male rat, leptin exhibits a high potency to stimulate FSH and
      LH release from hemipituitaries incubated in vitro, and increases the release of
      LHRH from MBH explants. LHRH and leptin release LH by activation of NOS in the
      gonadotropes. The NO released activates GC that releases cyclic GMP, which
      induces LH release. Leptin induces LH release in conscious, ovariectomized
      estrogen-primed female rats, presumably by stimulating LHRH release. At the
      effective dose of estrogen to activate LH release, FSH release is inhibited.
      Leptin may play an important role in induction of puberty and control of LHRH
      release in the adult as well.

PMID- 9785038
TI  - Sex- and stress-steroids interactions and the immune system: evidence for a
      neuroendocrine-immunological sexual dimorphism.
AB  - It is well established that sexual dimorphism exits within the immune system.
      Females have higher levels of immunoglobulins, greater antibody response to
      antigens, and higher incidence of autoimmune diseases, such as systemic lupus
      erythematosus, Grave's disease, and Hashimoto thyroiditis than males. Spontaneous
      autoimmune syndromes in mice are more prevalent and of greater severity in
      females compared with males, and the course of the disease can be modulated by
      changes in levels of gonadal steroids. A sexual dimorphism is also present in the
      pituitary-adrenal function: females have higher corticosterone levels and higher
      corticosteroidogenesis. In the context of the immune-neuroendocrine interactions,
      we investigated the effects of gonadectomy and sex hormone therapy on endotoxin
      stimulated hypothalamo-pituitary-adrenal axis. Whereas endotoxin-induced
      corticosterone release is invariable throughout the different stages of the
      oestrus cycle, gonadectomy in both male and female mice leads to enhanced adrenal
      and immune responses to endotoxin. Interestingly, these enhanced adrenal and
      immune responses can be completely reversed by testosterone treatment regardless
      of the sex of the mice. Studies performed over development confirm the role of
      endogenous testosterone in modulating the endotoxin-induced corticosterone
      secretion. Indeed, corticosterone response to endotoxin is maximal before puberty
      when endogenous testosterone levels are low and declines in postpubertal and
      adult mice. In conclusion, all these data support a sex steroid hormone basis for
      a neuroendocrine-immunologic sexual dimorphism.

PMID- 9785039
TI  - Regulation and role of intrapituitary IL-6 production by folliculostellate cells.
AB  - Interleukin-6, mainly produced by monocytes and macrophages is known to influence
      the secretion of anterior pituitary hormones and is, therefore, considered to
      play an important role in the interaction between the immune system and the
      endocrine system. However, IL-6 represents not only a lymphocyte message but is
      also produced within the anterior pituitary. Folliculostellate (FS) cells have
      been identified as the source of the intrapituitary IL-6 production in the normal
      pituitary, whereas in pituitary adenomas IL-6 is produced by the tumor cells
      themselves. The present review summarizes the knowledge about the regulation of
      the intrapituitary IL-6 synthesis and release in FS cells. Moreover, the possible
      roles of the intrinsic IL-6 production for function and growth of normal and
      adenomatous endocrine pituitary cells are discussed.

PMID- 9785040
TI  - The molecular basis for bidirectional communication between the immune and
      neuroendocrine systems.
AB  - IL-2 has analgesic effects in both central and peripheral nervous systems. There
      are two distinct domains in IL-2 molecule mediating immunologic and analgesic
      activity, respectively. The analgesic domain of IL-2 may be composed of the 44th
      Phe, 45th Tyr, 107th Tyr, and 117th Phe residues that are located closely in the
      tertiary structure of IL-2. The analgesic activity may be mediated through the
      analgesic domain interaction with opioid receptor. In addition to peptides,
      cytokines may directly bind to peptide receptors, other than their specific
      cytokine receptors themselves. Conversely, peptides may also interact with
      cytokine receptors. Thus, peptide neurotransmitters and hormones may serve as
      endogenous regulators of the immune system, and cytokines may also serve as
      neurotransmitters. Multiple actions might be mediated by interactions between
      distinct domains of bioactive molecules with different receptors.

PMID- 9785041
TI  - Immunological aspects of human growth hormone and prolactin.
AB  - We demonstrated that human lymphocytes secrete growth hormone and that the
      secretion is regulated in a different manner from that in the endocrine system.
      We could also show that some patients with hyperprolactinemia, especially
      asymptomatic type, have anti-prolactin autoantibody, which may be a novel case of
      hyperprolactinemia.

PMID- 9785042
TI  - HCG secretion by peripheral mononuclear cells during pregnancy.
AB  - Peripheral mononuclear cells (MNC) in culture release a biologically active hCG.
      This effect is detectable during pregnancy with a maximum between the 9th and
      16th wk. Peripheral MNC already secrete hCG between the 7th and 11th d after
      embryo transfer. The secretion of hCG is activated by the PKC-activator TPA. TPA
      induces hCG release into the medium, thus causing a decrease in intracellular hCG
      content. In contrast, db-cAMP inhibites hCG secretion into the medium. Protein
      synthesis inhibitors of transcription and translation suppress the production and
      secretion of hCG. Peripheral natural killer (NK) cells (CD56+/CD16+) and
      monocytes (CD14+) show the highest secretion rates. IL-1 beta, IL-4, IL-6, IL-10,
      TNF alpha, and GM-CSF stimulate, whereas IL-2 and INF gamma inhibit, the hCG
      secretion of mononuclear cells. Flow cytometric experiments with hCG antibody
      demonstrate a binding of hCG on the surface of monocytes more than lymphocytes.
      The binding capacity is improved during pregnancy. Different hCG bands are shown
      in the Western blot analysis. We could confirm the mRNA of beta hCG and alpha CG
      are in MNC as well in the placental control. Peripheral MNC, first and foremost
      NK cells and monocytes, produce and secrete hCG during pregnancy, which play an
      important role for the corpus luteum rescue during the early gestational age and
      possibly for the immunotolerance.

PMID- 9785043
TI  - Pituitary function in the acute phase response in domestic farm animals:
      cytokines, prostaglandins, and secretion of ACTH.
AB  - Contained in this report is a review of available data on pituitary cytokines in
      domestic species of agricultural importance. The concept is advanced that the
      pituitary gland is essential to appropriate generation of host defense mechanisms
      and thus should be considered among other tissues contributing to innate
      immunity. The functions of these intrapituitary cytokines, principally IL-6, are
      discussed in the context of potential regulation of the pituitary-adrenal axis
      (ACTH secretion) via intrapituitary PGE2 generation during the acute-phase
      response to infectious/inflammatory stimuli. Data from other species are cited as
      appropriate for comparative purposes and elaboration of proposed mechanisms.
      However, the scope of the review is not intended to comprehensively cover the
      vast literature on proinflammatory cytokines and prostaglandins generated
      peripherally and centrally during host responses to inflammatory stimuli.

PMID- 9785044
TI  - Neuroendocrine-immune interactions in the neonate.
AB  - Cytokine responses to lipopolysaccharides in neuroendocrine tissues are age- and
      tissue-dependent in neonatal pigs. Developmental differences in serum and tissue
      specific responses are not necessarily equivalent. Lower levels of cytokine gene
      expression in neuroendocrine tissues of early neonates potentially could
      influence neuroendocrine and immune responses to infection. The limited
      information on neuroendocrine-immune responses and interactions in neonatal farm
      animals presents significant challenges, as well as opportunities for new
      discoveries and improvements of livestock production.

PMID- 9785045
TI  - The role of neuroendocrine immune interactions in the initiation of humoral
      immunity in chickens.
AB  - The presence of neuroendocrine immune interaction in mammalian species has been
      studied extensively and has been established. However, such an interaction is not
      as well established in avian species. Furthermore, the role of such an
      interaction in the initiation of humoral immunity is not well understood.
      Therefore, the present studies were conducted to determine mechanisms involved in
      the initiation of humoral immunity in chickens. Cornell K-strain White Leghorn
      immature male chickens were used for all the experiments. Changes in hormonal and
      leukocyte profiles after antigen stimulation were studied. The ability of
      different leukocytes to produce ACTH was also investigated. It was concluded that
      the first step in the initiation of humoral immunity after antigen exposure is
      the release of interleukin-1 by macrophages, which in turn stimulates the
      production of CRF by hypothalamus and/or leukocytes. It is important to mention
      that CRF production could also be a direct effect of antigen stimulation. The CRF
      will then stimulate ACTH production by anterior pituitary and/or leukocytes. In
      addition, CRF will directly enhance lymphocyte activities in the spleen.
      Corticosteroid production will be stimulated by ACTH and will cause
      redistribution of lymphocytes from circulation to secondary lymphoid organs such
      as the spleen for antigen processing and eventual production of antibodies
      against the invading antigens. Finally, both ACTH and corticosteroids will later
      act in a negative feedback manner to regulate and control the process of antibody
      production by inhibiting lymphocyte activities and/or reducing the responsiveness
      to different stimuli.

PMID- 9785046
TI  - Endocrine modulation of physiological responses to catabolic disease.
AB  - Disease or endotoxemia alters the plasma concentrations of anabolic hormones,
      particularly growth hormone (GH) and insulin-like growth-factor I (IGF-I). In
      general, these hormones are inhibited during the catabolic disease state. A
      hypothesis has evolved that anabolic hormones might be useful in patients'
      recovery under these and other catabolic circumstances. The treatment of cattle
      with GH has provided significant improvement in the physiological response of the
      animals to the subsequent injection of bacterial lypopolysaccharide (LPS),
      perhaps via inhibition of tumor necrisis factor (TNF) release. However, this
      improved response to disease was not observed with animals treated with GH and
      infected with one of two parasitic organisms, Sarcocystis cruzi or Eimeria bovis.
      Recent attempts with other anabolic hormones, estradiol and progesterone, have
      proven remarkably effective in improving the adaptive physiological responses of
      calves to either E. bovis infection or to the injection of LPS. All animals
      displayed signs of infection, but the intensity and duration of symptoms were
      reduced. Although a mechanism is not yet known, there were no effects on TNF;
      cortisol; the percentages of lymphocytes expressing CD2, 4, or 8 antigens; or the
      production of antibodies.

PMID- 9785048
TI  - Cytokines as markers for infections and their effect on growth performance and
      well-being in the pig.
AB  - Exposure to micro-organisms commonly elicit the production of cytokines. These
      soluble factors enhance several innate immune functions that aim to limit the
      spread of infection. Further, many of the pro-inflammatory cytokines regulate the
      ensuing specific immune response. In addition to their effects on cells of the
      immune system, cytokines also are important regulators in the so called immune
      neuroendocrine network. The microbial structures that are necessary for induction
      of cytokine production are not conclusively determined but in general, bacteria
      preferentially induce the production of IL-1, TNF-alpha, IL-6, and IL-8, whereas
      virus induce the production of Type 1 interferons (IFN-alpha/beta). The onset of
      production of these cytokines is rapid, and several of them may reach systemic
      levels during a short period after infection. Thus, cytokines can serve as
      markers for ongoing infections and be used for discrimination between infections
      of bacterial or viral origin. Results from experimental and field studies show
      that serum IFN-alpha and IL-6 seem to be useful markers for ongoing (subclinical)
      viral and bacterial infections, respectively, in the pig. Consequently,
      demonstration of these cytokines can be valuable tools in heard health monitoring
      programs.

PMID- 9785047
TI  - Immune-endocrine interactions in agricultural species: chromium and its effect on
      health and performance.
AB  - The purported performance-enhancing effects of supplemental Cr, as elaborated in
      studies focusing on beef and dairy cattle models of agricultural stress, affect
      both immune and endocrine pathways. Furthermore, interactions between the immune
      and endocrine systems, associated with the actions of insulin and cortisol, may
      be coordinated through the production of regulatory cytokines. Unlocking the
      mechanism of action of Cr as a useful farm animal management tool may provide
      further understanding of the health and performance ramifications of immune
      endocrine interactions in agricultural species.

PMID- 9785049
TI  - Farmed deer: a large animal model for stress.
AB  - In the early classic period it was suggested by Heracleitus that a static
      unchanged state was not the natural condition, but rather that the capacity to
      undergo constant change was intrinsic to all living things. After that,
      Empedoeles, circa 500 BC, proposed that for living organisms to survive they
      require a harmonious mixture of elements. Hippocrates, around 400 BC, developed
      this concept further by suggesting that health is a state of harmonious balance
      of these elements, equating disease to a state of disharmony and introducing the
      concept that nature heals disease (Noysvn Fyseiw/atrui). Soon after, Epicurus
      extended these ideas to include among these healing forces, the mind, writing
      that imperturbability of mind is desirable. Claude Bernard introduced the concept
      of the milieu interieur or the internal physiologic environment, describing its
      constancy as essential in an external environment typified by its variability.
      Walter Cannon described Bernard's constancy as Homeostasis and identified the
      "fight or flight reflex," linking the adaptive response and catecholamine
      secretion, with extreme levels of activation-producing pathology. Selye outlined
      four stages of the stress response: 1) the "alarm reaction" characterized by an
      immediate activation of the sympathetic-adrenomedullary axis (SA); 2) a
      "resistance phase" characterized by hypothalamic pituitary-adrenal axis (HPA)
      activation; 3) a stage of adrenal hypertrophy, gastrointestinal ulceration, along
      with thymic and lymphoid atrophy; and 4) an exhaustion phase and finally death
      (1).

PMID- 9785050
TI  - Lipoprotein physiology.
AB  - Lipoproteins are spherical macromolecular complexes in which hydrophobic
      molecules of triglyceride and cholesteryl ester are enveloped within a monolayer
      of amphipathic molecules of phospholipids, free cholesterol, and apoproteins. The
      major lipoprotein classes include intestinally derived chylomicrons that
      transport dietary fats and cholesterol, hepatic-derived VLDL, IDL, and LDL that
      can be atherogenic, and hepatic- and intestinally derived HDL that are anti
      atherogenic. Apoprotein B is necessary for the secretion of chylomicrons (apo
      B48) and VLDL, IDL, and LDL (apo B100). Post-translational regulation of the
      assembly of apo B-containing lipoproteins by core lipid availability seems to be
      the major mechanism for variations in secretion. Plasma levels of VLDL
      triglycerides are determined mainly by rates of secretion and LPL lipolytic
      activity; plasma levels of LDL cholesterol are determined mainly by the secretion
      of apo B100 into plasma, the efficacy with which VLDL are converted to LDL and by
      LDL receptor-mediated clearance. Regulation of HDL cholesterol levels is complex
      and is affected by rates of synthesis of its apoproteins, rates of esterification
      of free cholesterol to cholesteryl ester by LCAT, levels of triglyceride-rich
      lipoproteins and CETP-mediated transfer of cholesteryl esters from HDL, and
      clearance from plasma of HDL lipids and apoproteins. Normal lipoprotein transport
      is associated with low levels of triglycerides and LDL cholesterol and high
      levels of HDL cholesterol. When lipoprotein transport is abnormal, lipoproteins
      levels can change in ways that predispose individuals to atherosclerosis.

PMID- 9785051
TI  - Genetics of lipoprotein disorders.
AB  - The study of lipoprotein metabolism has led to major breakthroughs in the fields
      of cellular physiology, molecular genetics, and protein chemistry. These advances
      in basic science are reflected in medicine in the form of improved diagnostic
      methods and better therapeutic tools. Perhaps the greatest benefit is the
      improved ability to identify at an early stage patients who are at high risk for
      atherosclerosis, providing clinicians the opportunity to proceed swiftly with
      intensive lipid-lowering therapy for the prevention of cardiovascular
      complications. Recent clinical trials have shown that such an approach is not
      only cost-effective but saves lives while improving the quality of life. They
      also emphasize the important role physicians can have in prevention. More than
      half of patients with premature CAD have a familial form of dyslipoproteinemia.
      This review of the genetics of atherogenic lipoprotein disorders underscores the
      importance of identifying major genetic defects. It also stresses the need to
      take into account multifactorial etiologies and clustering of risk factors, as
      well as gene-gene and gene-environment interactions in assessing the atherogenic
      potential of a lipid transport disorder. Table 2 summarizes the key points in the
      diagnosis, clinical implications, and treatment of the major inherited
      atherogenic dyslipidemias.

PMID- 9785052
TI  - The familial chylomicronemia syndrome.
AB  - The chylomicronemia syndrome is a disorder characterized by severe
      hypertriglyceridemia and fasting chylomicronemia. Genetic causes of the syndrome
      are rare and include deficiency of lipoprotein lipase (LPL), apolipoprotein C-II,
      and familial inhibitor of LPL. Patients with familial forms of
      hypertriglyceridemia in combination with secondary acquired disorders account for
      most individuals presenting with chylomicronemia. The clinical manifestations-
      lipid and other biochemical abnormalities--as well as treatment options for
      chylomicronemic patients are discussed.

PMID- 9785053
TI  - Lipoproteins and atherogenesis.
AB  - Like many complex disease processes, atherogenesis represents the interaction of
      an array of genetic and environmental factors. From nonhuman animal models to the
      investigation of epidemiologic factors in man, no single, overriding cause for
      the development of this indolent vascular disease has been identified. However,
      the cholesterol-enriched lipoprotein particles are closely tied to the
      development of the disease. The genetic and environmental influences on the
      concentrations of specific lipoprotein subspecies provide a context for
      identifying patients at risk as well as for developing effective therapeutic
      strategies to influence and prevent the sequelae of atherogenesis.

PMID- 9785054
TI  - Clinical trials of reducing low-density lipoprotein concentrations.
AB  - Much diverse evidence suggests that the plasma levels of low-density lipoprotein
      (LDL) cholesterol play a causal role in the pathogenesis of atherosclerotic
      coronary heart disease. Until recently, clinical trials of LDL lowering, while
      showing significant reductions in coronary heart disease (CHD) rates, were not
      entirely convincing and left some questions of long-term toxicity unresolved. The
      results of a series of new trials using members of the powerful statin class of
      drugs are now being reported. Whether they are primary or secondary prevention
      studies, they have been uniformly successful in reducing mortality and morbidity
      from CHD and even total mortality, and have decreased the need for
      revascularization procedures. Their effectiveness is apparent in many different
      subgroups such as women, diabetics, hypertensives, and in stroke prevention.
      Statin drugs also have proven to be remarkably safe over the duration of the
      studies. Angiographic studies show an impact on coronary or carotid lesions.

PMID- 9785055
TI  - Detection and evaluation of dyslipoproteinemia.
AB  - The National Cholesterol Education Program Adult Treatment Panel II guidelines
      recommend that all adults 20 years of age and older undergo testing to detect
      dyslipoproteinemia. Clinical trials have proven conclusively that lowering levels
      of low-density lipoprotein (LDL) cholesterol reduces coronary heart disease (CHD)
      incidence and mortality and total mortality in patients with and without CHD.
      There is persuasive scientific evidence to include young adults, women, and the
      elderly in the recommendation for cholesterol management. In adult without CHD,
      testing can begin with measurement of total cholesterol (TC) and high-density
      lipoprotein (HDL) cholesterol in the nonfasting state, and the results can then
      be used to determine which individuals require a fasting lipoprotein analysis
      (total cholesterol, HDL, triglycerides, and estimation of LDL); patients with
      known CHD should begin with lipoprotein analysis. The level of LDL cholesterol
      and the presence or absence of other CHD risk factors determine the need for
      cholesterol-lowering therapy. Patients with known CHD are at highest risk for a
      CHD event and have the lowest LDL cholesterol goal (100 mg/dL); patients without
      CHD but with elevated LDL-C (130 mg/dL) and two or more other CHD risk factors
      are at high risk for developing CHD and have an LDL cholesterol goal of less than
      130 mg/dL; patients free of CHD with high LDL cholesterol (160 mg/dL) but fewer
      than two other risk factors have a lower CHD risk and an LDL cholesterol goal of
      less than 160 mg/dL. Elevated triglyceride may be a marker for other factors that
      increase CHD risk. Raising HDL cholesterol, while not proven to be of benefit, is
      reasonable in patients at high CHD risk.

PMID- 9785056
TI  - Dyslipoproteinemia and diabetes.
AB  - Dyslipidemia in patients with diabetes constitutes quantitative and qualitative
      abnormalities in all classes of lipoproteins and may be a significant contributor
      to the high risk of atherosclerosis in these patients. A step-care approach to
      therapy of diabetic dyslipidemia, including hygienic measures (diet and increased
      physical activity), hypoglycemic drugs, and lipid-lowering drugs, is recommended.
      The choice of lipid-lowering drugs depends on severity of hypertriglyceridemia.
      Statins and bile-acid-binding resins are the choice of therapy for diabetic
      dyslipidemia; however, for severely hypertriglyceridemic patients, fibric acid
      derivatives should be used. Nicotinic acid worsens hyperglycemia and, therefore,
      should be avoided. The value of estrogen replacement therapy in postmenopausal
      women with diabetes has not been established.

PMID- 9785057
TI  - Women, dyslipoproteinemia, and estrogens.
AB  - The most common cause of death in both men and women is coronary atherosclerosis,
      although atherosclerotic death in women occurs 5 to 10 years later than it does
      in men. Major risk factors predict coronary risk in both. Available evidence
      suggests that women benefit from cholesterol lowering just as men do. The role of
      exogenous estrogenic compounds in favorably affecting lipoprotein levels and
      promoting antiatherogenesis in both men and women is a promising area for future
      research.

PMID- 9785058
TI  - Evaluation and management of dyslipoproteinemia in children.
AB  - The major goal of the evaluation and management of DLP in children is to provide
      safe and effective therapy with lifestyle modification. There is a strong
      rationale for the initiation of DLP treatment in childhood to limit the earliest
      stages of atherosclerosis, to establish lifelong lifestyle changes in diet and
      activity, and to limit the acquisition of additional CVD risk factors such as
      smoking and obesity. The NCEP has recommended screening for children with a
      parent with total cholesterol of 240 mg/dL or greater or a parent or grandparent
      with onset of CVD before age 55 years. Clinical evaluation and management are
      based on an LDL-C level of 130 mg/dL or greater. This approach to screening has a
      low sensitivity to identify children with DLP. Initial therapy is with a step 1
      diet followed by the step 2 diet if necessary. Medications are reserved for older
      children with LDL-C of 190 mg/dL or greater after diet therapy or 160 mg/dL or
      greater with other CVD risk factors.

PMID- 9785059
TI  - The role of cholesterol management in coronary disease risk reduction in elderly
      patients.
AB  - This article discusses the various factors that must be taken into account and
      balanced when making decisions about particular therapies for the management of
      high-serum cholesterol in older persons.

PMID- 9785060
TI  - Drugs causing dyslipoproteinemia.
AB  - Diuretics and beta-blockers have a strong tendency to affect serum lipids
      adversely, whereas the peripherally acting alpha-blocking agents consistently
      result in beneficial effects. Most of the other antihypertensive agents (calcium
      channel blockers, ACE inhibitors, angiotensin II receptor antagonists, and drugs
      that act centrally) are lipid neutral. The effect of steroid hormones varies with
      the drug, dose, and route of administration. In general, androgens lower HDL-C
      and have a variable effect on LDL-C. The effects of progestins vary greatly
      depending on their androgenicity, and estrogens are beneficial except when
      hypertriglyceridemia occurs with oral estrogens. Glucocorticoids raise HDL-C and
      may also increase triglycerides and LDL-C. Retinoids increase triglycerides and
      LDL-C and also reduce HDL-C. Interferons can cause hypertriglyceridemia.
      Following organ transplantation, a dyslipidemia often ensues. This is caused in
      part by the medications used to prevent rejection (glucocorticoids, cyclosporine,
      and FK-506) and requires close attention and, in some patients, drug therapy to
      prevent coronary artery disease.

PMID- 9785061
TI  - Factors affecting high-density lipoproteins.
AB  - Although it is well established that a low-circulating level of high-density
      lipoprotein (HDL) cholesterol is strongly associated with the likelihood of
      developing atherosclerotic coronary heart disease (CHD), the causal nature of
      this association has not been shown. Low levels of HDL cholesterol frequently are
      associated with other CHD risk factors, whose correction, often by hygienic
      means, may reduce CHD risk with minimal risk of adverse side-effects. However,
      other recommended hygienic interventions may lower HDL cholesterol levels.
      Specific safe and effective drugs for correcting a low HDL cholesterol level are
      not available and the potential value of specific pharmacologic treatment of this
      condition in the treatment or prevention of CHD remains unproven. Thus, while HDL
      measurement should be incorporated routinely in risk-assessment, intervention
      efforts should focus primarily on lowering low-density lipoprotein cholesterol.

PMID- 9785062
TI  - Diet, lipoproteins, and coronary heart disease.
AB  - Current dietary recommendations to decrease coronary heart disease (CHD) risk in
      the general population include reduction of total fat intake to less than or
      equal to 30% of energy, saturated fat to less than 10% of energy, and dietary
      cholesterol to less than 300 mg/day. Further restrictions in saturated fat to
      less than 7% of energy and in dietary cholesterol to less than 200 mg/day are
      indicated for those individuals with elevated low-density lipoprotein (LDL)
      cholesterol concentrations. Under controlled conditions, such diets reduce LDL
      cholesterol by 15% to 20%. However, in the out-patient setting, only 5% to 10%
      reductions in LDL cholesterol have been achieved, and large variability in
      dietary response is observed due to differences in compliance, as well as to
      genetic heterogeneity. This article reviews epidemiologic studies and dietary
      intervention trials that support a direct relationship between diet,
      lipoproteins, and CHD risk, with the ultimate goal of providing a framework for
      dietary management of the hyperlipidemic patient.

PMID- 9785063
TI  - Informed consent to anaesthesia.

PMID- 9785064
TI  - 150 years of anaesthesia--a long way to perioperative medicine: the modern role
      of the anaesthesiologist.

PMID- 9785065
TI  - Post-tetanic burst count and train-of-four during recovery from vecuronium
      induced intense neuromuscular block under different types of anaesthesia.
AB  - Recovery of neuromuscular blockade after vecuronium 0.2 mg kg-1 was measured by
      post-tetanic burst count (PTBC) and train-of-four (TOF) in 120 adult patients
      anaesthetized by one of four techniques: neuroleptanaesthesia or one minimum
      alveolar concentration of isoflurane, enflurane, or sevoflurane. Onset of
      recovery was taken when there was reflex movement in response to carinal
      stimulation. The time course of recovery measured by burst count was similar for
      all four types of anaesthesia. Recovery of each of the twitches of the TOF was
      significantly shorter under neuroleptanaesthesia than under isoflurane,
      enflurane, or sevoflurane anaesthesia [times to return of T1 were 41.4 +/- 5.4,
      51.5 +/- 10.6, 52.2 +/- 10.0, or 55.3 +/- 11.2 min (mean +/- SD). P < 0.05]. The
      burst count at the onset of reflex movement was less under neuroleptanaesthesia
      than under isoflurane, enflurane, or sevoflurane anaesthesia (16.3 +/- 4.8, 26.7
      +/- 6.7, 27.7 +/- 6.8, 28.0 +/- 8.4, P < 0.05). The ratio of first twitch to
      control twitch at the onset of reflex movement was the same for all four types of
      anaesthesia.

PMID- 9785066
TI  - Intercostal nerve blockade with a mixture of bupivacaine and phenol enhance the
      efficacy of intravenous patient-controlled analgesia in the control of post
      cholecystectomy pain.
AB  - Prolonged nerve conduction blockade has been proposed to result from the summed
      effects of charged and neutral local anaesthetics. Thirty-seven patients were
      randomly allocated to receive intravenous patient-controlled analgesia alone or
      combined with intercostal blockade (T7-T11) with a mixture of 0.45% bupivacaine
      and 0.6% phenol for post-cholecystectomy analgesia. Adequacy of pain relief was
      measured by patient scores on a 10-cm visual analogue scale and by dose-demand
      ratio, amounts of loading dose and total consumption of morphine and also the
      duration of patient-controlled analgesia in each group. No differences were found
      between groups in post-operative scores, dose-demand ratios and loading doses of
      morphine. However, in the combined treatment group, a significantly lower total
      consumption of morphine (P < 0.05), associated with a shorter duration of patient
      controlled analgesia (P < 0.02) and a decreased mean number of unsuccessful
      demands (P < 0.001) were recorded. Intercostal blockade with bupivacaine-phenol
      supplements intravenous patient-controlled analgesia for post-cholecystectomy
      pain relief.

PMID- 9785067
TI  - Cardiovascular responses, arterial oxygen saturation and plasma catecholamine
      concentration during upper gastrointestinal endoscopy using conscious sedation
      with midazolam or propofol.
AB  - Hypoventilation as a consequence of deep intravenous sedation is the most
      frequently reported cause of cardiac arrest during upper gastrointestinal
      endoscopy (UGIE). Haemodynamic stress can contribute to myocardial ischaemia;
      therefore, this study was designed to observe prospectively the cardiorespiratory
      changes during UGIE using either midazolam or propofol for conscious sedation.
      Thirty-four patients, aged 50 years and older, ASA physical status I-III,
      scheduled for elective UGIE with sedation, were studied. Oxygen saturation, heart
      rate, non-invasive blood pressure and Holter ECG were recorded continuously
      starting 15 min before sedation until 15 min after the endoscopy. In addition,
      plasma catecholamine concentrations were determined. The results of this study
      are consistent with previous reports that cardiopulmonary events may occur during
      endoscopy, with or without sedation. Both midazolam and propofol sedation may
      provide some protection against haemodynamic stress in response to insertion and
      manipulation of the endoscope, but sedation can also contribute to the occurrence
      of hypoxaemia.

PMID- 9785068
TI  - A prospective study comparing intravenous tenoxicam with rectal diclofenac for
      pain relief in day case surgery.
AB  - In a prospective, randomized, double-blind study, we compared intravenous
      tenoxicam with rectal diclofenac for post-operative pain relief after day case
      arthroscopy or laparoscopic sterilization. Intravenous tenoxicam (40 mg) was
      administered as a single bolus at induction, or rectal diclofenac (100 mg) was
      administered immediately after induction. Both groups were similar with respect
      to age, weight, sex of the patients, the operation performed and the operative
      time. There were no significant differences observed between the groups for pain
      scores at 30 min, 60 min and 24 h post-operatively. The time to first analgesic
      requirement, the dose of pethidine administered and total analgesic requirements
      in the first 24 h post-operatively were equivalent in both groups. In view of the
      similar efficacy of both of these drugs, patient preference and ease of
      administration, the use of tenoxicam is appropriate in many patients undergoing
      day case surgery.

PMID- 9785069
TI  - A double-blind study of axillary brachial plexus block by 0.75% ropivacaine or 2%
      mepivacaine.
AB  - Axillary brachial plexus block using 20 mL of 0.75% ropivacaine or 2% mepivacaine
      was compared in a prospective, randomized, double-blind study of two groups of 15
      patients. The times to onset of sensory and motor block and to resolution of
      motor block, as well as the time to onset and degree of post-operative pain were
      recorded by an observer blinded to the identity of drug. Times to onset of
      sensory block were similar in the two groups (ropivacaine 10 min, mepivacaine 8
      min). Resolution of motor block in the operated hand and the time to first
      requirement of post-operative analgesia occurred later with ropivacaine (9 h 50
      min and 10 h) than with mepivacaine (3 h 50 min and 6 h), P < 0.01 for both
      measurements. Nine patients who received ropivacaine and two patients who
      received mepivacaine did not require further post-operative analgesia (P < 0.05).
      Ropivacaine is less toxic than other long-acting local anaesthetics, and 0.75%
      ropivacaine may be better for brachial plexus block when fast onset is required
      and prolonged pain relief is useful.

PMID- 9785070
TI  - Effects of sevoflurane and isoflurane on free radical formation in the post
      ischaemic reperfused heart.
AB  - Sevoflurane has been reported to generate oxygen free radicals. We have
      investigated whether sevoflurane or isoflurane enhances oxygen free radical
      formation in the post-ischaemic reperfused heart. An isolated rat heart-lung
      preparation was used. Thirty male Wistar rats were allocated to four groups:
      control, no drug, 2.5% sevoflurane and 1.4% isoflurane. The heart was perfused
      initially at a cardiac output of 30 mL min-1 and a mean arterial pressure of 70
      mmHg. Ten minutes after the start of perfusion, the heart was rendered globally
      ischaemic for 10 min by reducing the preload and afterload to zero. Then, the
      heart was reperfused for 10 min. At the end of reperfusion, the heart was freeze
      dried for 6 days. The perfusate blood was collected just before and just after
      ischaemia and at the end of reperfusion. The formation of hydroxyl radicals in
      perfusate blood and heart was measured with high-performance liquid
      chromatography using salicylic acid. Hydroxyl radicals react with salicylic acid,
      yielding 2,3-, 2,4-, 2,5- and 3,4-dihydroxybenzoic acid (DHBA). Before and after
      ischaemia, there were no significant differences in cardiac output, systolic
      pressure, heart rate and right arterial pressure among the groups. The
      concentrations of 2,3-, 2,4-, 2,5- and 3,4-DHBA in the perfusate blood after
      ischaemia and reperfusion were significantly higher than those before ischaemia
      in all groups. However, there were no differences in the DHBA levels among
      groups. This study indicates that sevoflurane and isoflurane do not enhance
      hydroxyl radical formation in the post-ischaemic reperfused heart.

PMID- 9785071
TI  - Total intravenous anaesthesia with gamma-hydroxybutyrate (GHB) and sufentanil in
      patients undergoing coronary artery bypass graft surgery: a comparison in
      patients with unimpaired and impaired left ventricular function.
AB  - The haemodynamic effects of anaesthesia with gamma-hydroxybutyrate
      (GHB)/sufentanil for elective coronary artery bypass grafting (CABG) were
      investigated and compared in patients with unimpaired left ventricular function
      (ejection fraction > or = 45%, left ventricular end diastolic pressure < or = 16
      mmHg) and patients with impaired left ventricular function. In 38 consecutive
      patients scheduled for CABG (21 with unimpaired and 17 with impaired left
      ventricular function), anaesthesia was induced with etomidate, sufentanil and
      pancuronium. After tracheal intubation, the lungs were normoventilated (end tidal
      Pco2 4.9-5.6 kPa) with an oxygen-air mixture (Fio2 0.5). Total intravenous
      anaesthesia was maintained with GHB (20 mg kg-1 h-1 after a 'priming dose' of 40
      mg kg-1) and sufentanil (2 micrograms kg-1 h-1). Haemodynamic measurements were
      made after induction of anaesthesia and at various times in the prebypass period.
      Patients in both groups showed similar haemodynamic trends. Mean arterial
      pressure showed a maximum reduction of 10%, whereas heart rate and right- and
      left-sided filling pressures remained unchanged within the groups after the
      induction of anaesthesia. Cardiac index remained unchanged in both groups,
      although values differed between the groups. A total of 14 out of 21 patients
      (67%) with unimpaired and 10 out of 17 patients (59%) with impaired ventricular
      function required supplementary administration of opioids to control temporary
      hypertension after sternotomy. No episodes of myocardial ischaemia were detected
      during the study period using ST segment analysis (leads II and V5). The results
      of this study suggest that GHB provides adequate haemodynamic conditions in the
      prebypass period and may be a suitable agent for TIVA also in patients with
      impaired left ventricular function undergoing CABG.

PMID- 9785072
TI  - Increased nausea and dizziness when using tramadol for post-operative patient
      controlled analgesia (PCA) compared with morphine after intraoperative loading
      with morphine.
AB  - Thirty-eight ASA I-III patients undergoing lower abdominal operations were
      randomly allocated to receive either morphine (group M, patient-controlled
      analgesia bolus = 1 mg of morphine) or tramadol (group T, patient-controlled
      analgesia bolus = 10 mg of tramadol) for post-operative patient-controlled
      analgesia (PCA) after receiving morphine intraoperatively. There were no between
      group differences in the pain, sedation or vomit scores. The nausea scores were
      significantly higher in group T in the initial 20 h and between 32 and 36 h (P <
      0.01, 0-4 and 8-12 h; P < 0.05, 4-8, 12-16, 16-20 and 32-36 h). The incidence of
      dizziness was also significantly higher in group T (68.4% vs. 31.6%, group T vs.
      group M, P < 0.05). There was no difference in the overall satisfaction. We
      conclude that the use of tramadol, compared with morphine, for post-operative PCA
      after intraoperative loading with morphine is associated with more nausea and
      dizziness, but with similar sedation, quality of analgesia and patient
      satisfaction.

PMID- 9785073
TI  - Artificial oxygen carriers.
AB  - The clinical availability of artificial oxygen carriers (AOCs) would result in
      profound alterations in transfusion medical practice. Rapid progress in the
      scientific and technological development of AOCs has advanced to a critical stage
      at which safe and effective alternatives to the transfusion of red blood cells
      are emerging. Haemoglobin- and perfluorocarbon-based oxygen carriers are under
      current clinical investigation. Artificial oxygen-carrying solutions, by virtue
      of their acellular structure, can be used to transport oxygen to ischaemic
      tissues that cannot otherwise be reached by cellular blood components. Organs
      awaiting transplantation can be preserved for a long time after perfusion with
      AOCs and tumour susceptibility to chemo- and radiotherapy is increased. The use
      of AOCs is therefore not confined to their use as red blood cell substitutes, but
      may find a wide spectrum of interdisciplinary applications.

PMID- 9785074
TI  - Cardiovascular effects of Org 9487 under isoflurane anaesthesia in man.
AB  - The cardiovascular effects of Org 9487 during isoflurane anaesthesia have been
      evaluated using three doses around its ED90 for neuromuscular blockade, i.e. 1 mg
      kg-1, 2 mg kg-1 and 3 mg kg-1. Heart rate increased to 110%, 115% and 118% in
      patients receiving 1 mg kg-1, 2 mg kg-1 and 3 mg kg-1 respectively. There were no
      significant effects on systolic and diastolic blood pressures for the two lower
      dose groups. Patients receiving Org 9487 3 mg kg-1 displayed significant
      decreases in systolic and diastolic blood pressures (91% and 82% of the control
      values respectively). Except for heart rate in the group receiving 3 mg kg-1, all
      measurements returned to baseline after a maximum of 15 min. Six patients
      experienced a transient increase in airway pressure after administration of Org
      9487, which was accompanied by a decrease in oxygen saturation in two out of six
      subjects, but there was no audible wheezing. These episodes were self-limiting
      and required no treatment. There were no other adverse reactions to this drug
      during this study.

PMID- 9785075
TI  - Post-operative nausea and vomiting following orbital hydroxyapatite implant
      surgery.
AB  - Fifty-five consecutive patients undergoing a short-stay ophthalmic operation
      (orbital hydroxyapatite implantation) were recruited over 1 year to assess the
      frequency and duration of post-operative nausea and vomiting over 7 days. The
      incidence of nausea and vomiting in hospital was recorded. Patients scored their
      nausea and vomiting four times daily at home. By the end of the first day after
      surgery, 31 (75%) patients had experienced mild to severe nausea. Eighteen (38%)
      patients became nauseated on five or more occasions. Nineteen (35%) patients had
      vomited by the end of the first day after surgery and, over 7 days, 24 (43%)
      patients had vomited on one or more occasion. Three patients reported that they
      had vomited during the journey home. Vomiting was not correlated with pain or a
      past history of post-operative nausea and vomiting. However, there was a
      statistically significant correlation between nausea and pain. The high incidence
      of nausea and vomiting observed in this study appears to provide additional
      evidence of an oculo-emetic reflex. The timing of discharge and appropriate
      patient education are discussed.

PMID- 9785077
TI  - Catecholamine-resistant cardiovascular collapse after propofol, atracurium and
      gentamicin.
AB  - A 43-year-old male received intravenous propofol, atracurium and gentamicin and
      experienced cardiovascular collapse with the features of an acute drug reaction.
      Prolonged cardiopulmonary resuscitation with fluids and large amounts of
      adrenaline and noradrenaline led to full recovery without neurological deficit.
      No biochemical abnormality was detected.

PMID- 9785076
TI  - The impact of audit in a district general hospital on post-operative nausea and
      vomiting after major gynaecological surgery.
AB  - An audit of post-operative nausea and vomiting (PONV) was undertaken in 935
      female patients who used morphine patient-controlled analgesia (PCA) for pain
      relief after major gynaecological operations in a district general hospital. We
      investigated retrospectively five different antiemetic policies and a reference
      group without policy from January 1993 to July 1995. The department's
      computerized audit system was used to analyse the observations. At the beginning
      of the audit, the incidence of nausea and vomiting was as high as 71.5%. But as a
      consequence of this audit, a departmental policy was adopted 3 years later, which
      had an incidence of PONV of only 51.7%. During this time the compliance with
      antiemetic protocols increased from 41% to 76%. There was significantly less PONV
      if an antiemetic protocol was followed (P = 0.002). This emphasizes the
      importance of corporate involvement in the development, formulation and
      evaluation of departmental protocols if compliance is to be high. We conclude
      that audit as a corporate effort improves the acceptance of departmental
      protocols. This reduces PONV significantly irrespective of the type of antiemetic
      drug used.

PMID- 9785078
TI  - Severe non-ketotic hyperosmolar coma--intensive care management.
AB  - We report a case of non-ketotic hyperosmolar coma, which presented with blood
      sugar levels far exceeding any previously recorded in the literature. The patient
      developed acute renal failure, probably because of rhabdomyolysis, which was
      successfully managed with continuous veno-venous haemofiltration. He developed
      blurring of vision resulting from biochemical changes, which was managed
      conservatively. We discuss the mechanisms of causation of the renal failure and
      visual blurring.

PMID- 9785079
TI  - General anaesthetic for a pilonidal sinus excision in a patient with hereditary
      angio-oedema.
AB  - Hereditary angio-oedema is an autosomal dominant condition resulting in a
      deficiency of C1 esterase inhibitor protein in serum. The condition is
      characterized by oedematous attacks in the skin, mucous membranes and
      gastrointestinal tract triggered by mental and physical stress. We present the
      rare case of a young girl with known hereditary angio-oedema and spina bifida
      occulta being admitted for an elective pilonidal sinus excision. This case
      presented different challenges for the anaesthetists and surgeons.

PMID- 9785080
TI  - Hemiplegia following general anaesthesia: an unusual presentation of migraine.
AB  - We report the case of a 33-year-old woman who developed a dense hemiplegia
      immediately after an uncomplicated general anaesthetic for diagnostic
      laparoscopy. She had a history of recurrent hemiplegic migraine with a strong
      family history. Her migraine was normally associated with visual disturbances and
      a unilateral headache followed by a left-sided weakness such that she was unable
      to walk. Symptoms would last up to 24 h. Her post-operative state was atypical of
      her normal migraine, in that she had no headache or visual disturbance and
      initially all four limbs were affected.

PMID- 9785081
TI  - Anaphylactoid reaction induced by pancuronium during general anaesthesia.

PMID- 9785083
TI  - Unexpected failure of a catheter mount.

PMID- 9785082
TI  - Masseter spasm during induction of anaesthesia using propofol and fentanyl.

PMID- 9785084
TI  - A complication of percutaneous tracheostomy while using the Combitube for airway
      control.

PMID- 9785085
TI  - Just another explanation for: 'Horner's syndrome following low-dose epidural
      infusion for labour' presented by H. G. W. Paw.

PMID- 9785086
TI  - Re: Procalcitonin: a new parameter for the diagnosis of bacterial infection in
      the perioperative period. Oczenski et al., Eur J Anaesthesiol 1998; 15: 129-132.

PMID- 9785087
TI  - Now that the cloud has lifted Armenia steps towards the European standard.

PMID- 9785088
TI  - A biologically motivated partitioning of mortality.
AB  - For over a century, actuaries and biologists working independently of each other
      have presented arguments for why total mortality needs to be partitioned into
      biologically meaningful subcomponents. These mortality partitions tended to
      overlook genetic diseases that are inherited because the partitions were
      motivated by a paradigm focused on aging. In this article, we combine and extend
      the concepts from these disciplines to develop a conceptual partitioning of total
      mortality into extrinsic and intrinsic causes of death. An extrinsic death is
      either caused or initiated by something that orginates outside the body of an
      individual, while an intrinsic death is either caused or initiated by processes
      that originate within the body. It is argued that extrinsic mortality has been a
      driving force in determining why we die when we do from intrinsic causes of
      death. This biologically motivated partitioning of mortality provides a useful
      perspective for researchers interested in comparative mortality analyses, the
      consequences of population aging, limits to human life expectancy, the progress
      made by the biomedical sciences against lethal diseases, and demographic models
      that predict the life expectancy of future populations.

PMID- 9785089
TI  - Treatment of human ulcers by application of macrophages prepared from a blood
      unit.
AB  - Decubital ulcers contribute to morbidity and mortality in elderly patients.
      Macrophages play a major role in the process of wound healing. We compared the
      efficacy of local treatment of decubital ulcers in elderly patients using
      macrophages prepared from a blood unit, vs. conventional treatments. Patients
      with decubital ulcers (n = 199) hospitalized during one year in a Geriatric
      Hospital in Israel, were included in the study. The ulcers of 72 patients
      (average age 82), who provided informed consent, by themselves or by family, were
      treated by local injection of macrophages prepared from a blood unit in a closed
      sterile system. The remaining 127 patients (average age 79) were treated
      conventionally and served as controls. No exclusion criteria were applied. Only a
      completely healed ulcer was considered a positive outcome of treatment. In the
      macrophage-treated group 27% (36 out of 131 ulcers) were healed compared to 6%
      (15 out of 248) in the control group (p < 0.001). There was also a significantly
      faster healing in the experimental group (p < 0.02). No side effects were noted.
      We conclude that Macrophages prepared from a blood unit, in cost-effective,
      closed, sterile system, are significantly more effective than conventional
      methods for the treatment of ulcers in elderly patients.

PMID- 9785090
TI  - Central markers of body fat distribution are important predictors of plasma
      lipids in elderly men and women.
AB  - We determined the contribution of body fat distribution, peak VO2, fat mass, and
      dietary intake to variation in plasma lipids in elderly individuals. Volunteers
      were a healthy cohort of older Caucasian women (n = 75, mean age +/- SD, 72 +/- 5
      years) and older men (n = 101, 72 +/- 5 years). We determined fat mass from
      underwater weighing, fat patterning from waist circumference, as well as
      peripheral and truncal skinfolds, exercise capacity from peak VO2, and dietary
      intake from three-day food diaries. Plasma lipid levels were measured in the
      fasting state and included total cholesterol, high density lipoprotein (HDL-C),
      low density lipoprotein (LDL-C), and fasting triglycerides. Older women weighted
      less than older men, but had higher fat mass, truncal, and peripheral skinfolds.
      Waist circumference and peak VO2 were lower in older women than older men. Older
      women had higher total cholesterol (217 +/- 31 vs. 197 +/- 30; p < 0.01), HDL-C
      (54 +/- 12 vs. 49 +/- 14; p < 0.05), and LDL-C (133 +/- 26 vs. 121 +/- 27; p <
      0.01) when compared with older men. No gender differences were noted in fasting
      triglycerides. Truncal skinfolds were the best predictor of plasma lipids in
      older men, accounting for between 9% and 30% (r2) of the variation in plasma
      lipids. Similarly, in older women, central markers of fatness (i.e., waist
      circumference and truncal skinfolds) were the best predictors of plasma lipids
      (r2 = 3% to 24%). Total fat mass, peak VO2 and dietary intake were not
      independent predictors of plasma lipids in older men and women. Indices of
      central body fatness, rather than total fat mass, peak VO2 or dietary intake are
      stronger predictors of plasma lipids in healthy older men and women.

PMID- 9785091
TI  - Age-dependent changes of K-elastin stimulated effector functions of human
      phagocytic cells: relevance for atherogenesis.
AB  - Effector functions of the elastin receptor on human phagocytic cells from young
      and older individuals were studied. In cells of young healthy subjects the
      elastin peptides, the agonists of receptor, stimulated both superoxide anion
      release from PMNs and phagocytosis of coated human red cells by monocytes.
      Elastin appeared to inhibit the cholesterol synthesis in monocytes, measured by
      the incorporation of 14C-acetate. In comparison with phagocytic cells of young (<
      or = 25 +/- 6 years) subjects. PMNs of elderly donors (> or = 75 +/- 10 years)
      bore a similar number of binding sites for soluble elastin peptides, and the
      affinity of the elastin receptor was unchanged as shown by Scatchard analysis.
      The phagocytosis of coated human red cells stimulated by elastin peptides was
      also similar in the two age groups. However, several differences were found
      between phagocytic cells of young and elderly donors 1) PMNs of elderly released
      increased amounts of elastase from both resting and elastin peptide stimulated
      cells, and 2) monocytes of elderly showed a lack of inhibition of cholesterol
      synthesis by elastin peptides when maintained in cholesterol-free medium. These
      changes in effector functions of phagocytic cells from elderly donors might
      contribute to the age-dependent increase of susceptibility to the development of
      atherosclerotic lesions.

PMID- 9785092
TI  - Reassessment of immortalization complementation group D.
AB  - Previous somatic cell hybridization studies have assigned many human cell lines
      to one of four complementation groups (A-D) for immortalization. We report here
      that the A1698DM cell line, which contains selectable markers and has previously
      been defined as the immortalization group D representative, was derived from T24
      cells rather than A1698. A1698DM did not undergo senescence when fused with cell
      lines assigned to groups A, B, or C. This raises the possibility that this cell
      line has undergone further evolution and lost multiple putative senescence genes
      so that it is now unable to complement any, or most, other cell lines for
      senescence. Cell lines previously assigned to group D may, therefore, be
      heterogeneous with respect to the genetic changes that resulted in their
      immortalization. This has important implications for strategies to clone
      senescence genes based on complementation groups.

PMID- 9785093
TI  - Effect of age and caloric restriction on insulin receptor binding and glucose
      transporter levels in aging rats.
AB  - We report on the effect of age and chronic caloric restriction (CR) on insulin
      binding and glucose transporter content in both diaphragm and heart muscle
      membrane of young (11 months), mid-age (17 months), and old (29 month) ad libitum
      fed and CR Brown-Norway rats. The control animals received rat chow ad lib and CR
      animals were allowed 60% of ad libitum food. The CR regimen was initiated at four
      months of age and the animals were maintained on their respective diets until
      necropsy. There was no effect of age on insulin binding for either ad libitum or
      CR animals at each age evaluated. Caloric restriction significantly lowered
      insulin levels at each age studied when compared to the ad libitum-fed rats.
      However, CR animals were noted to have increased insulin binding (p < 0.001)
      compared to ad libitum-fed animals at each age for diaphragm muscle. For the
      heart, there appeared to be a decreased binding, particularly at higher insulin
      concentrations, in CR-fed animals. There was no net change in Glut-1 or Glut-4
      levels for heart muscle membrane, or Glut-4 levels for diaphragm muscle membrane
      between ad libitum or CR animals. This data indicates that caloric restriction
      may have tissue-specific effects for insulin receptor binding, and that the
      improved insulin sensitivity in CR states is not a result of altered glucose
      transporter protein content.

PMID- 9785094
TI  - Aging decreases the production of PGI2 in rat aortic endothelial cells.
AB  - It has been suggested that progressive pathophysiologic modifications of
      endothelium are associated with aging. Aging has been shown to influence some
      specific functions at the cellular level. In the present study, the effects of
      aging on levels of prostacyclin (PGI2) production were examined in cultured rat
      aortic endothelial cells from young (six-week-old) and old (100-week-old) Wistar
      rats. The level of PGI2 production from rat aortic endothelial cells decreased
      significantly with increasing age, suggesting decreased function of the
      endothelial cells. The production of PGI2 stimulated by thrombin was decreased in
      old rat aortic endothelial cells compared to young rat aortic endothelial cells,
      whereas there was no difference in the rate of intracellular calcium mobilization
      caused by thrombin. These data indicate that aging nonuniformly affects both
      basal and agonist-induced levels of PGI2 production in rat aortic endothelial
      cells, and that this diminution in PGI2 production may be related to the age
      related potentiation of various thrombotic events.

PMID- 9785095
TI  - The effect of exercise training in a cold environment on thermoregulation in
      adult and aged C57BL/6J mice.
AB  - We studied the effect of exercise training in cold environment (six weeks of
      daily, one-hour runs on a treadmill at ambient temperature of 6 +/- 1 degrees C
      at 60-65% of VO2max) on cold-induced metabolic heat production, heat loss, and
      cold tolerance in adult and aged C57BL/6J male mice. In adult mice, exercise
      training in cold environment resulted in greater cold-induced heat production and
      cold tolerance without changes in heat loss, similar to the effects of daily cold
      exposure without exercise. In aged mice, daily cold exposures did not affect cold
      tolerance and cold-induced heat production, but exercise training in the cold
      resulted in greater cold-induced heat production and cold tolerance. Heat loss in
      aged mice increased similarly after both repeated cold exposures and exercise
      training in the cold. Therefore, mechanisms of effect of exercise training on
      cold tolerance are different in adult and aged animals. Exercise training in cold
      environment does not affect cold-induced heat production and cold tolerance in
      adult mice, but improves them in aged animals.

PMID- 9785096
TI  - An assessment of behavioral aging in the Mongolian gerbil.
AB  - Male Mongolian gerbils (Meriones unguiculatus) 14-54 months old (n = 77) were
      evaluated in a battery of psychomotor (open field, locomotor, and runwheel
      activity, rotorod performance) and learning (one-way active avoidance in a
      straight runway and in 14-unit T-maze performance) tests. Body weight and seizure
      activity were also monitored. According to linear regression analysis, runwheel
      activity decreased with age; and the number of errors in the 14-unit T-maze
      increased as a function of age (ps < 0.05). None of the other behavioral measures
      or body weight were significantly correlated with age. This gerbil strain
      (Tumblebrook Farms; West Brookfield, MA) tended to be very prone to seizures with
      64% of the gerbils experiencing at least one seizure while being tested. Seizures
      tended to occur when the gerbil was exposed to a novel situation (e.g., initial
      weighing, placement on the rotorod). An age-related decline in some aspects of
      psychomotor and learning performance was observed, suggesting the gerbil as an
      additional mammalian model of aging. The high incidence of seizure activity
      presented a complicating and confounding variable to the interpretation of the
      results of the behavioral tests used in the present study. Interventions to
      control seizure activity (e.g., systematic, controlled breeding; adaptation to
      apparati) in this model will likely increase its viability as a mammalian model
      of aging.

PMID- 9785097
TI  - Gompertz growth in number dead confirms medflies and nematodes show excess
      oldster survival.
AB  - A recent report (Easton, 1995) showed that, at least for Mediterranean fruit
      flies, a Gompertz growth equation based on the increase in number of individuals
      that die is a better predictor of survival data than is the classical Gompertz
      survivorship model based on the decrease in number that survive (analysis of
      medfly data of Carey et al., 1992). In the growth model, the rate of increase of
      the number dead (i.e., the death rate) decreases exponentially with age. The poor
      fit of the classical model predicts "excess survival" of older members, but, when
      the scale of the better-fitting growth model is increased 2400x, such excess is
      now also evident as a small but distinctly separate cohort of the medfly
      subjects. The smaller population appears to be about 0.01% of the larger, and the
      death rate decreases about one-fourth as fast. Survival of the nematode C.
      elegans (Brooks et al., 1994) is also better predicted by the growth model, which
      also shows excess survival of the worms at great age.

PMID- 9785099
TI  - Binding modes of PCBs to a degrading enzyme: a receptor-mapping study.
AB  - The binding site of a PCB-degrading enzyme was mapped using the published data on
      biodegradation rates of individual PCB congeners by the Acinetobacter P6 strain.
      For this purpose an approach allowing for multiple binding modes of individual
      congeners, resulting from the symmetry of the biphenyl skeleton, was used. The
      effect of substitution patterns and conformational flexibility of individual
      congeners on their binding to a protein were investigated. The resulting map of
      the binding site is described by three parameters that indicate the importance of
      positions 4, 5', 5, 2' in a basic substitution pattern, the first two being
      favourable while the other two unfavourable for binding. An incorporation of
      conformational energy dependences of individual ligands into the model showed
      that ligand's conformation is either not a limiting factor for binding or that
      ligands bind in their relaxed conformations.

PMID- 9785098
TI  - Molecular clusters in water protein solutions in the presence of heavy metal
      ions.
AB  - For the first time, formation of macromolecular protein clusters in the presence
      of heavy metal ions were observed by the light scattering method. Conditions of
      the formation and destruction of such clusters were investigated. The clusters
      mass has a maximum value at the isoelectric point of the protein and increases
      with the ionic strength of the solution. Formation of clusters in the presence of
      toxic heavy metals in living cells is believed to have an essential physiological
      meaning. The molecular mechanisms of such clusters formation are discussed.

PMID- 9785100
TI  - Studies on interactions between metmyoglobin and heparin.
AB  - The complex formation between metmyoglobin and heparin was investigated by
      absorbance and fluorescence spectroscopy as well as differential scanning
      microcalorimetry. In acidic pH region, three distinct complexes detected by
      absorbance measurements are formed depending on pH and time of equilibration. The
      kinetics of the conformational transition of metmyoglobin-heparin complex
      equilibrated at neutral pH observed after pH change to acidic region comprises
      two steps. During the first step, characterized by rapid changes of the
      absorption spectra (approximately 5 minutes) as well as fluorescence intensities,
      reversible transition with pK = 6.5 +/- 0.1 occurs and the first type of the
      complex forms. Below pH 6.2 the transition with pK = 5.7 +/- 0.1 is observed and
      the second type of the complex is formed. During the second slow step, the third
      type of the complex formed after 30 minutes of equilibration is characterized by
      a spectrum corresponding to low-spin form without protein axial ligand bound. At
      neutral pH and 25 degrees C, the interaction between metMb and heparin only
      slightly alters absorption and fluorescence spectra. On the other hand, the
      formation of metMb-heparin complex is established from the decrease of the
      transition temperature from 80.4 +/- 0.5 degrees C to 74.7 +/- 0.5 degrees C.
      Moreover, the binding of heparin prevents the aggregation of the protein at
      isoelectric point resulting in a considerable increase in the reversibility of
      thermal denaturation.

PMID- 9785101
TI  - Kinetic evidence of the existence of a stable enzyme-glycosyl intermediary
      complex in the reaction catalyzed by endotransglycosylase.
AB  - Xyloglucan-endotransglycosylase (XET) is an enzyme involved in the metabolism of
      xyloglucan (XG) in plant cell walls and seeds. This enzyme acts both as a
      hydrolase and as a transglycosylase by transferring the fragments of xyloglucan
      molecules to other XG molecules or xyloglucan-derived oligosaccharides (XGOs). In
      this work, we studied the kinetics of interaction between XET and XG. The
      equilibrium in the reaction of XG degradation by XET was found to depend on the
      initial enzyme concentration and the availability of suitable glycosyl acceptors.
      After reaching the equilibrium, the addition to the reaction mixture of XET or
      XGOs caused further degradation of XG, and a new equilibrium with a higher degree
      of XG depolymerization was established. These results indicated that in the
      course of XG depolymerization, the enzyme is bound in a relatively stable,
      temporarily inactive enzyme-glycosyl complex and this complex is decomposed by
      transferring its glycosyl moiety to suitable oligosaccharide acceptor. Mouse
      polyclonal antibody against XET linked to AffiGel 10 (Affi-Ab) adsorbed both XET
      and XET-XG complex but not [3H]XG alone. XET immobilized onto Affi-Ab was able to
      bind [3H]XG and catalyze transglycosylation in presence of XGOs.

PMID- 9785102
TI  - Effect of ouabain on the breakdown of adenine nucleotides in glucose-depleted
      nucleated red blood cells. Characterization of ATPase.
AB  - The present report confirms the presence of Na(+)-K(+)-Mg2+ ATPase in the
      erythrocyte membranes of the frog Rana balcanica (previously Rana ridibunda)
      (Schneider et al. 1993; Sofianidou et al. 1994). The Na(+)-K(+)-Mg2+ ATPase
      activity was 60% reduced by the presence of ouabain. The pH optimum was 8.0, the
      optimum Mg2+:ATP concentration ratio was 2.2:1. The existence of an ATPase with a
      high K(m) for ATP (1.48 mmol/l) was postulated. At pH 7.4 and 8.0, the adenine
      nucleotide pattern of glucose-depleted erythrocytes showed a characteristic
      reduction in ATP contents. Adenine nucleotide concentrations were higher at pH
      7.4 than at pH 8.0. Ouabain inhibited ATP breakdown at both pH values studied.
      The strongest inhibition was observed at pH 7.4. The decline of the total
      contents of adenine nucleotides appears to be determined by the rate of AMP
      breakdown.

PMID- 9785103
TI  - Tryptophan fluorescence of mitochondrial uncoupling protein.
AB  - Mitochondrial uncoupling protein (UcP) contains two tryptophans buried in
      transmembrane alpha-helices: Trp-173 at the matrix end of fourth alpha-helix and
      Trp-280 on the sixth alpha-helix. However, the steady-state emission of isolated
      UcP exhibited properties unusual for alpha-helices: maximum close to that of free
      tryptophan emission and low quantum yield of 0.04. The former suggests prevailing
      tryptophan contacts with hydrophilic residues and confirms Trp-173 proximity to
      the water/membrane interface and Trp-280 location near a water-filled nucleotide
      binding-site cavity. The latter might indicate that transmembrane segments are
      not true alpha-helices. Measured depolarization factor of 0.6 suggests also their
      "breathing". Analysis of UcP emission decays, measured by time-correlated-single
      photon-counting, yielded components 0.4-0.6 ns, 2.2-3 ns and 9-10 ns (or
      alternatively 0.1, 1.5, 4.3 and 12.2 ns; or 0.1-0.3, 1.2, 3.7 and 10.5 ns), very
      similar to those of free tryptophan in water, where the longest component belongs
      to anionic form. Hence, such an "anionic" conformation must exist in UcP, perhaps
      as a consequence of charge-transfer complexes between Trp-173 & Lys-174 and Trp
      280 & Arg-276. Moreover, N-ethylmaleimide modification, known to induce
      conformational changes, prolonged the "10 ns" component, decreased quantum yield
      to 0.03 without changes in emission spectra, while slightly shifting absorption
      to red and increasing tyrosine exposure to water.

PMID- 9785105
TI  - Upper respiratory infections--otitis media.

PMID- 9785104
TI  - Ca(2+)-induced inhibition of sodium pump: noncompetitive inhibition in respect of
      magnesium and sodium cations.
AB  - Calcium inhibits the activity of the (Na+/K+)-ATPase from dog kidney in a dose
      dependent manner. Other 2A group cations of the periodic table such as Sr2+ and
      Ba2+ were able to inhibit the ATPase activity but to a lesser degree. Any
      considerable competition between Ca2+ (Ba2+, Sr2+) ions and magnesium or sodium
      ions could not be detected using enzyme kinetic analysis. Thus, the above three
      inhibitory acting ions depress the ATPase activity of sodium pump by interaction
      with loci distant from the sodium and potassium binding sites. This suggests that
      the (Na+/K+)-ATPase molecule contains an inhibitory acting binding site for
      calcium. This putative binding site could recognize magnesium ions as well as
      calcium, strontium and barium ions. The specificity of the binding site may
      describe herein be secured by a structure complementary to the coordination
      structure of Ca2+, Ba2+ and Sr2+ ions characterized by coordination number 8.
      Mg2+ ions can form coordination structure with a maximum coordination number 6,
      and do not interact specifically with this binding site.

PMID- 9785106
TI  - Daily oral grepafloxacin vs. twice daily oral doxycycline in the treatment of
      Chlamydia trachomatis endocervical infection.
AB  - OBJECTIVE: To compare the efficacy and safety of a 7-day course of treatment with
      oral grepafloxacin, 400 mg once daily, and oral doxycycline, 100 mg twice daily,
      in patients with chlamydial cervicitis. METHODS: Women aged 18 years or older
      attending 17 sexually transmitted disease clinics in the United States who had
      clinical signs of mucopurulent cervicitis or who had a recent positive culture or
      nonculture test for Chlamydia trachomatis or who had contact with a male partner
      with a positive culture for C. trachomatis were enrolled into this randomized,
      double-blind, active-controlled clinical study. The diagnosis of chlamydial
      cervicitis was based on culture for C. trachomatis. Patients were randomized to
      receive a 7-day course of treatment with either oral grepafloxacin, 400 mg once
      daily, or oral doxycycline, 100 mg twice daily. Response to therapy was assessed
      3-8 days and 21-28 days after completion of treatment. The primary measure of
      efficacy was eradication of C. trachomatis at the 21-28 day follow-up visit.
      Clinical success, defined as improvement or complete resolution of the signs and
      symptoms of cervicitis, was a secondary measure of efficacy. RESULTS: Of the 451
      female patients enrolled, 228 received grepafloxacin and 223 received
      doxycycline. In all, 154/451 (35%) patients were evaluable at the 21-28 day
      follow-up (81 who received grepafloxacin and 73 who received doxycycline).
      Microbiologic and clinical success rates demonstrated the equivalence of the two
      treatments. The C. trachomatis eradication rates were 96.3% (78/81) and 98.6%
      (72/73) for patients receiving grepafloxacin or doxycycline, respectively. The
      two study drugs were also equivalent in resolving clinical signs and symptoms,
      with clinical success rates of 88.9% (64/72) and 89.5% (51/57) for patients
      treated with grepafloxacin and doxycycline, respectively. Both drugs were well
      tolerated, with 47% of patients receiving grepafloxacin and 46% of patients
      receiving doxycycline experiencing drug-related adverse events, none of which was
      serious. CONCLUSIONS: Seven days of treatment with oral grepafloxacin, 400 mg
      once daily, was as effective as 7 days of treatment with oral doxycycline, 100 mg
      twice daily, in patients with cervicitis caused by C. trachomatis. Both agents
      were well tolerated and had comparable safety profiles. Grepafloxacin's once
      daily dosing regimen may offer advantages in terms of patient compliance.

PMID- 9785107
TI  - Initial and repeat screening for Chlamydia trachomatis during pregnancy.
AB  - OBJECTIVES: The objective of this study is to determine the prevalence of
      Chlamydia trachomatis and risk factors for positive repeat tests in a high-risk
      population presenting for early prenatal care. METHODS: We completed a
      retrospective cohort study of 2,484 women who initiated prenatal care prior to 20
      weeks gestation, delivered, and received testing for cervical C. trachomatis at
      Grady Memorial Hospital or a Grady-affiliated clinic between July 1, 1993 and
      December 31, 1994. We calculated adjusted odds ratios (OR) for selected risk
      factors for a positive initial test and for a positive subsequent test after an
      initial negative test. RESULTS: The prevalence of C. trachomatis was 14.8%. At
      initial testing, 10.4% of the women were positive. If the initial test was
      negative, 5.7% had a positive subsequent test; but if the initial test was
      positive, 32.0% had a positive subsequent test (P < 0.001). The variables
      significantly and independently associated with a positive initial test were
      black race/ethnicity, age less than 25, unmarried, and less than a high-school
      education (adjusted OR of 1.66, 3.53, 2.18, and 1.81, respectively). Variables
      significantly and independently associated with a positive subsequent test after
      a negative initial test were white race/ethnicity, black race/ethnicity, age less
      than 25, and less than a high-school education (adjusted OR 8.69, 7.77, 4.12, and
      2.27, respectively). CONCLUSIONS: In our inner-city population, most pregnant
      women have risk factors suggesting the need to rescreen for C. trachomatis in the
      second half of pregnancy.

PMID- 9785108
TI  - Compliance with universal precautions: knowledge and behavior of residents and
      students in a department of obstetrics and gynecology.
AB  - OBJECTIVES: To assess the knowledge of universal precautions for the delivery and
      operating rooms by residents and students and to evaluate their use of universal
      precautions. STUDY DESIGN: Obstetrics and gynecology (ob/gyn) residents (n = 30)
      and students (n = 31) from an inner-city, teaching hospital were polled by
      anonymous questionnaire to assess their knowledge of the appropriate barrier
      equipment for certain ob/gyn procedures. To determine actual compliance with
      universal precautions, 459 ob/gyn procedures were observed. We noted the use of
      appropriate barrier equipment for each procedure: gloves for pelvic exam and face
      shields, gowns, gloves, and booties for vaginal delivery, cesarean delivery, and
      dilation and curettage. The True Epistat statistical software program was used to
      perform simple regression analysis. RESULTS: Thirty residents (100%) knew the
      appropriate barrier equipment required for each type of procedure performed. One
      student (< 1%) did not know that booties were appropriate for the surgical
      procedures. Rationale for lack of compliance with universal precautions elicited
      by the questionnaire included time constraints (64%), inconvenience (52%), and
      presumption that patient was not infected (34%). The observed rate of compliance
      with universal precautions by participants indicates that individual compliance
      was inversely related to the years of experience (overall compliance rate of
      students was 96%; for first-year residents, 92%, second-year residents, 89%,
      third-year residents, 84%, fourth-year residents, 78%; r = -0.9918, P = 0.0009).
      CONCLUSIONS: Knowledge regarding universal precautions was nearly 100%, while
      overall observed compliance was only 89%. Compliance with universal precautions
      was better among students (96%) than among residents (88%). Compliance with
      universal precautions was inversely related to years of experience.

PMID- 9785109
TI  - Prevalence of cervicovaginal infections during gestation and accuracy of clinical
      diagnosis.
AB  - OBJECTIVES: The aim of this study was to establish the prevalence of
      cervicovaginal infections in normal third-trimester pregnant women and evaluate
      the accuracy of clinical diagnosis. METHOD: A total of 328 pregnant women were
      followed at the Prenatal Outpatient Clinic of the Department of Obstetrics and
      Gynecology at the School of Medical Sciences, Universidade Estadual de Campinas
      (UNICAMP), Brazil, from October 1991 to February 1993. The clinical diagnosis was
      based on the characteristics of the vaginal discharge, and the etiological
      diagnosis was based on bacterioscopy of the vaginal secretion and direct
      immunofluorescence for Chlamydia trachomatis. The data were analyzed
      statistically, determining the sensitivity, specificity, and positive and
      negative predictive value of the clinical diagnosis related to the laboratory
      diagnosis of the different infections. RESULTS: The prevalence of infection was
      39.6% (Candida albicans, 19.2%; bacterial vaginosis, 9.5%; intermediate vaginal
      flora, 6.7%; Chlamydia trachomatis, 2.1%; and vaginal trichomoniasis, 2.1%). The
      accuracy of clinical diagnosis was low, with sensitivity between 50% and 65% and
      specificity around 60%, with the exception of trichomoniasis, which showed a
      sensitivity of 100% and chlamydia, with a sensitivity of 0% and a specificity of
      100%. CONCLUSION: The accuracy of the clinical diagnosis of infections was low,
      specifically with respect to the positive predictive value. The results
      demonstrate the need for specific testing of cervicovaginal infections at
      prenatal visits. Reliance on simple vaginal examination results in a low yield
      for detection of vaginal infections.

PMID- 9785110
TI  - Congenital syphilis after treatment of maternal syphilis with a penicillin
      regimen exceeding CDC guidelines.
AB  - BACKGROUND: Although congenital syphilis usually occurs as a result of a failure
      to detect and treat syphilis in pregnant women, failures of the currently
      recommended regimen to prevent congenital syphilis have been reported. CASE: This
      report describes an infant with congenital syphilis despite maternal treatment
      with a regimen exceeding current CDC guidelines. CONCLUSION: Regardless of the
      regimen used to treat syphilis during pregnancy, clinicians should recognize the
      possibility of occasional treatment failures and the importance of adequate
      follow-up of infants at risk for congenital syphilis.

PMID- 9785111
TI  - Bilateral tubo-ovarian abscesses four years after total abdominal hysterectomy.
AB  - BACKGROUND: Pelvic inflammatory disease (PID) is a common gynecologic disorder.
      One known complication of PID is tubo-ovarian abscess (TOA) formation. The
      predominant theory on TOA formation postulates that an ascending infection from
      the cervix through the uterus to the fallopian tubes and ovaries results in
      abscess formation. Other theories include seeding via a hematogenous infection,
      diverticular disease, and appendicitis. CASE: A 39-year-old female patient with
      abdominal pain was referred to our institution and was found to have a pelvic
      mass. After a thorough evaluation, surgical exploration revealed the presence of
      TOA. No evidence of gastrointestinal disease was present. The patient's history
      was significant for an uncomplicated total abdominal hysterectomy for benign
      disease of the uterus four years prior. Abscess cultures grew Streptococcus
      intermedius. CONCLUSION: This case reports the rare occurrence of TOA in a
      patient who had undergone an abdominal hysterectomy four years prior to
      presentation. If the patient reports a surgical history of prior hysterectomy,
      TOA is often stricken from consideration. Although unlikely, adnexal abscess
      formation should be considered in the differential diagnosis of a patient with
      abdominal pain and a pelvic mass, even with a remote history of hysterectomy.

PMID- 9785112
TI  - Do early-life events permanently alter behavioral and hormonal responses to
      stressors?
AB  - Early-life stimulation (e.g., brief handling) attenuates the behavioral and
      neuroendocrine responses to stressors encountered in adulthood, particularly with
      respect to activation of hypothalamic-pituitary-adrenal (HPA) activity. In
      contrast, if neonates were subjected to a more severe stressor, such as
      protracted separation from the dam or exposure to an endotoxin, then the adult
      response to a stressor was exaggerated. These early-life experiences program HPA
      functioning, including negative feedback derived from stimulation of hippocampal
      glucocorticoid receptors, and corticotropin-releasing hormone (CRH) and arginine
      vasopressin (AVP) coexpression in PVN neurons, to modify the response to
      subsequent stressor experiences. The persistent variations of HPA activity
      observed in handled/stimulated animals may stem from alterations in dam-pup
      interactions (e.g. increased arched-back feeding, licking, grooming). In addition
      genetic makeup is critical in determining stress reactivity. For instance,
      BALB/cByJ mice are more reactive to stressors than C57BL/6ByJ mice, exhibiting
      greater HPA hormonal alterations and behavioral disturbances. BALB/cByJ also fail
      to acquire a spatial learning response in a Morris water-maze paradigm, which has
      been shown to be correlated with hippocampal cell loss associated with aging.
      Early-life handling of BALB/cByJ mice prevented these performance deficits and
      attenuated the hypersecretion of ACTH and corticosterone elicited by stressors.
      The stressor reactivity may have been related to maternal and genetic factors.
      When BALB/cByJ mice were raised by a C57BL/6ByJ dam, the excessive stress
      elicited HPA activity was reduced, as were the behavioral impairments. However,
      cross-fostering the more resilient C57BL/6ByJ mice to a BALB/cByJ dam failed to
      elicit the behavioral disturbances. It is suggested that genetic factors may
      influence dam-pup interactive styles and may thus proactively influence the
      response to subsequent stressors among vulnerable animals. In contrast, in
      relatively hardy animals the early-life manipulations may have less obvious
      effects.

PMID- 9785113
TI  - Long-term behavioural and neuroendocrine changes in Roman high-(RHA/Verh) and low
      (RLA-Verh) avoidance rats following neonatal handling.
AB  - Roman high-(RHA/Verh) and low-(RLA/Verh) avoidance rats, originally selected and
      bred for rapid vs poor acquisition of a two-way active avoidance response, differ
      in emotional reactivity and coping style. These differences are associated with
      particular neuroendocrine and neurochemical characteristics. New data are
      presented here to show that the behavioural changes specifically induced by
      neonatal handling, i.e. decreased emotional reactivity, are associated with
      marked changes in the neuroendocrine responses of (hyperemotional) RLA/Verh rats
      to a novel environment. Eight months after neonatal handling, self-grooming
      behaviour, a reliable marker of emotional reactivity in this line of rats, was
      significantly decreased in RLA/Verh rats. Defecation scores were also
      significantly reduced in both lines. Moreover, there was a significant reduction
      in prolactin and corticosterone release following exposure to a novel environment
      in neonatally-handled RLA/Verh rats as compared to control, non-handled rats. No
      effects on prolactin and corticosterone release were observed in RHA/Verh rats.
      There was also no apparent effect of neonatal handling on coping style i.e.
      RLA/Verh rats did not increase their spontaneous exploration of novel
      environments. Thus, the phenotypic expression of basic traits of (high)
      neuroendocrine/emotional reactivity was specifically modulated by neonatal
      handling in RLA/Verh rats, whereas both the (hypoemotional) RHA/Verh rats as well
      as coping style in both lines remained unaffected. Changes in emotional
      reactivity were still apparent at 12 months of age when rats from the same groups
      were tested for hyponeophagia. These results suggest that psychogenetically
      selected lines such as RHA/RLA rats are suitable animal models to investigate
      interactions between genes and the environment in determining individual
      sensitivity to stress and coping styles, as well as potential vulnerability (or
      resistance) to the development of maladaptive syndromes similar to anxiety and
      mood disorders in humans.

PMID- 9785114
TI  - Corticosterone release in response to repeated, short episodes of neonatal
      isolation: evidence of sensitization.
AB  - Repeated isolation of neonatal rats produces persistent changes in physiology and
      behavior. In Experiment 1, we examined changes in plasma corticosterone (CORT)
      levels as a possible mechanism for the effects of isolation. Pups that were
      isolated from their mother and the nest for 1 h per day on postnatal days (PND) 2
      9 were compared to control litters of pups that were either nonhandled or handled
      but not isolated. On PND 2, compared to nonhandled pups, handled pups had
      elevated CORT levels that returned to baseline levels within 30 to 60 min of
      return to the home cage. No significant elevation of CORT levels were found in
      handled pups on PND 9. The CORT levels of isolated pups were over twice those of
      nonhandled pups on PND 2 and four times those of nonhandled pups on PND 9. In
      Experiment 2, we investigated whether the increased CORT release in response to
      isolation on PND 9 was the result of the pups' treatment on the previous six days
      as against an effect of maturation. Plasma CORT levels were measured in rat pups
      that were either isolated, handled or nonhandled on PNDs 2-8 during the
      conditions of isolation, handling and nonhandling on PND 9. There were no
      differences among the groups in basal plasma levels of CORT. Handling on PND 9
      did not result in elevated CORT levels in any of the groups. All three groups
      showed a significant increase in plasma CORT levels after isolation on PND 9.
      However, the CORT response to isolation of pups previously isolated on PND 2-8
      were significantly higher than pups that were either handled or nonhandled on
      PNDs 2-8. Thus, daily episodes of isolation potentiate the hypothalamic-pituitary
      adrenal response to stress.

PMID- 9785115
TI  - Postnatal maternal separation during the stress hyporesponsive period enhances
      the adrenocortical response to novelty in adult rats by affecting feedback
      regulation in the CA1 hippocampal field.
AB  - The aim of the present experiment was to study the effects of early postnatal
      maternal separation on behavioural and adrenocortical responses to novelty in
      rats tested as adults. Sprague-Dawley rat pups were exposed to daily maternal
      separation (5 h/day) from postnatal day 2 to 6, during the stress hyporesponsive
      period. Since this procedure requires physical contact with the animals, a first
      control group of daily handled pups was introduced. A second control group,
      consisting of pups never handled or separated from the mother, was also
      considered. At postnatal day 45, the rats were tested in a two-compartment
      exploratory apparatus: the maternally separated and the non-handled rats, whose
      behavioural performance did not differ, showed higher emotional behaviour when
      compared with the handled rats (P < 0.05), suggesting that the handling procedure
      but not maternal separation improved the capacity to cope with novelty.
      Corticosterone plasma levels were found to be higher in the maternally separated
      rats than in the other two groups (P < 0.05), either at resting conditions or at
      30 min after novelty exposure (P < 0.05). Levels of nuclear glucocorticoid
      receptor immunoreactivity in the CA1 hippocampal field were shown to be regulated
      by novelty exposure, as expected, in both the handled and the non-handled rats
      but not in the maternally separated rats. In conclusion, repeated maternal
      separation periods of 5 h/day during the first week of life produced long-lasting
      effects on the hippocampal regulation of the hypothalamic-pituitary
      adrenocortical axis, which appear to be associated with increased responsiveness
      to stress stimuli in adulthood.

PMID- 9785116
TI  - Prenatal stress: consequences of glucocorticoids on hippocampal development and
      function.
AB  - Prenatally stressed offspring exhibit a variety of physiological and behavioral
      alterations. This paper highlights those alterations associated with prenatal
      stress-induced elevations in glucocorticoid secretion. Three major alterations
      are identified that may be produced by glucocorticoid-induced actions on the
      developing hippocampus. Changes include reductions in steroid receptors that bind
      endogenous glucocorticoids, enhanced secretion of stress hormones and increased
      reactivity or emotionality in stressful situations. Some of these alterations may
      be ameliorated by early postnatal environmental manipulations such as adoption
      and handling procedures. These latter results suggest that prenatal stress
      induced effects of glucocorticoids extend into the early postnatal period to
      produce long-term hippocampal and behavioral alterations. Support for this
      hypothesis is based on studies demonstrating that the hippocampus undergoes
      considerable maturational changes during the early postnatal period such as
      establishing the regional distribution of corticosteroid receptor densities and
      development of hippocampal dentate gyrus cells as well as cholinergic systems.
      Hippocampal corticosteroid receptors are involved in the regulation of
      glucocorticoid negative feedback and hippocampal dentate gyrus and cholinergic
      development are influenced by endogenous glucocorticoids and are implicated in
      the development of defensive or stress-induced behavior. The developing
      hippocampus appears especially vulnerable to alterations induced by prenatal
      stress-induced elevations in glucocorticoids that continue to produce their
      effects throughout the early postnatal period.

PMID- 9785117
TI  - Maternal stress induces synaptic loss and developmental disabilities of
      offspring.
AB  - Mild prenatal stress affects the serotonergic system in the hippocampus of rat
      offspring. Pregnant rats were daily exposed to mild stress treatments (consisting
      of crowding and saline injection) during days 15 to 21 of pregnancy. Their
      offspring were assessed by a series of biochemical, histological and behavioral
      tests. On 35 days after birth, 5-hydroxytryptamine (5-HT) level was decreased by
      17% (P < 0.05), whereas 5-hydroxyindolacetic acid (5-HIAA) level was increased by
      18% (P < 0.05) in the offspring of prenatally stressed rats. The metabolic rate
      (5-HIAA/5-HT) was increased by 49% (P < 0.01). Synaptic density in the
      hippocampus of prenatally stressed offspring was also decreased by 32% (P <
      0.0001) on postnatal day 35. There was no significant group difference in the
      spatial learning acquisition test of the Morris water maze; however, in the
      reversal task, prenatally stressed 5-week old rats spent more time than control
      animals searching for the platform of the pool. Escape latency in the cued test
      showed no significant difference. Together with data in our previous studies,
      that have shown 5-HT to facilitate synapse formation and maintenance in the
      central nervous system, synaptic loss is suggested to occur in relation to
      changes of 5-HT system in the hippocampus of prenatally stressed offspring. This
      may be associated with reported changes in behavior and learning ability in
      prenatally stressed offspring.

PMID- 9785118
TI  - Prenatal experience and postnatal stress modulate the adult neurosteroid and
      catecholaminergic stress responses.
AB  - Allopregnanolone (3 alpha-hydroxy-5 alpha-regnan-20-one) is a neuroactive steroid
      recently shown to be involved in the neurochemical stress response via its
      positive modulation of the GABAA receptor complex. This experiment investigated
      the effects of postnatal stress (daily maternal separation during the first week
      of life) on the subsequent adult response to a stressor (10 min forced swim) in
      Long-Evans rats from one of three prenatal treatment groups (alcohol, pair-fed
      and control). Indices of stress response were allopregnanolone concentrations in
      plasma, cortex and hippocampus, and dopamine and norepinephrine concentrations in
      prefrontal cortex, nucleus accumbens and striatum. Females had higher levels of
      allopregnanolone than males in both plasma and brain. Prenatal alcohol exposure
      combined with early maternal separation stress resulted in an increase in the
      endogenous levels of allopregnanolone in the prefrontal cortex and hippocampus of
      adult offspring in response to a stressor compared to subjects without a prior
      history of postnatal stress; this effect was greater in females. This increased
      allopregnanolone was also associated with decreased dopamine and norepinephrine
      levels in the prefrontal cortex. In the prenatal alcohol-exposed offspring,
      postnatal maternal separation blunted the increase in dopamine levels in the
      striatum seen in both control groups. Postnatal maternal separation increased
      norepinephrine levels in the nucleus accumbens regardless of prenatal experience,
      while in the prefrontal cortex only prenatal diet condition (pair-feeding and
      alcohol) resulted in lower norepinephrine levels. The results of this experiment
      suggest that experience, both pre- and postnatal, can have long-term consequences
      for the developing neurochemical responses to stressors.

PMID- 9785119
TI  - The distribution of radiolabeled corticotropin-releasing factor in pregnant rats:
      an investigation of placental transfer to the fetuses.
AB  - Stress during gestation can have serious consequences on the development of the
      fetus. Many of these effects appear to be mediated by hormones of the
      hypothalamic-pituitary-adrenal (HPA) axis. Corticotropin-releasing factor (CRF),
      released by the hypothalamus during times of stress serves to activate release of
      pituitary hormones and is also present in low levels in rat plasma. Moreover, the
      uterus contains significant quantities of CRF at implantation sites, probably
      from local sources. Therefore, the possibility exists that CRF may cross the
      placenta and activate the fetal HPA axis. However, the ability of CRF to cross
      the placenta has not been demonstrated. In the present study, pregnant rats were
      administered radiolabeled CRF intraperitoneally, and the distribution of the
      labeled product was determined in the fetuses and various maternal organs. High
      levels of activity were observed in the pregnant female's uterus, adrenals, heart
      and the placentae, but only background levels of activity were detected in the
      maternal brain. Very low levels of activity were observed in the fetuses,
      indicating that the transfer of CRF across the placenta is greatly restricted.
      These findings suggest that maternal CRF has little or no direct effect on the
      developing fetus during gestational stress.

PMID- 9785120
TI  - Stress inhibits the proliferation of granule cell precursors in the developing
      dentate gyrus.
AB  - The granule cell population of the dentate gyrus is produced predominantly during
      the postnatal period in rats. Previous studies have shown that experimental
      increases in the levels of adrenal steroids suppress the proliferation of granule
      cell precursors during the first postnatal week, the time of maximal neurogenesis
      in the dentate gyrus. These findings raise the possibility that stressful
      experiences that elevate adrenal steroid levels may inhibit the production of
      granule neurons, and thus alter the development of the dentate gyrus. To test
      this possibility, we exposed naive rat pups to the odors of a known predator,
      adult male rats, and examined both plasma corticosterone levels and the number of
      3H-thymidine labeled cells in the dentate gyrus. A single exposure of rat pups to
      adult male rat odor elevated corticosterone levels immediately and diminished the
      number of 3H-thymidine labeled cells in the granule cell layer by 24 h later.
      These results suggest that stressful experiences suppress the production of
      granule neurons in the developing dentate gyrus.

PMID- 9785121
TI  - Anterior pituitary response to stress: time-related changes and adaptation.
AB  - A wide array of physical and psychological stressors alter the secretion of
      anterior pituitary hormones. However, both the qualitative and the quantitative
      features of the stressors as well as its duration markedly influence the final
      endocrine response. In addition, among all anterior pituitary hormones, only ACTH
      and prolactin levels appear to reflect the intensity of the stress experienced by
      the animals. Although physical stressors show a somewhat specific neuroendocrine
      profile, the response of the pituitary-adrenal (PA) and sympathomedulloadrenal
      axes are common to almost all stressors. After an initial stimulatory effect of
      stress, an inhibition of all anterior pituitary hormones, except ACTH, can be
      found provided the stressor is intense enough. The mechanisms responsible for
      this biphasic response to stress are likely to be located at sites above the
      pituitary. When the animals are repeatedly exposed to the same stressor, some
      behavioural and physiological consequences of stress exposure are reduced,
      suggesting that the animals become adapted to the stimulus. This process has been
      also termed habituation. Among all the pituitary hormones, only ACTH and
      prolactin levels are reduced as a consequence of repeated exposure to the same
      (homotypic) stressor, although some negative results have been reported. However,
      it has been recently reported that subtle changes in the characteristics of the
      stressors or in their regularity can greatly influence adaptation, and these
      factors might explain failure to find adaptation of ACTH and prolactin in some
      works. Habituation of ACTH and prolactin, when observed, appears to be specific
      for the chronically applied stressor so that the potentiality of the PA axis and
      prolactin to respond to a novel (heterotypic) stressor can be preserved. In the
      case of the PA axis, an intact or potentiated response to a novel stressor is
      observed in spite of presumably negative feedback exerted by daily stress-induced
      glucocorticoid release and the high resting levels of glucocorticoids. This
      phenomenon has been termed as facilitation and can be unmasked alternating
      stress. Although with the exception of the PA axis, developmental aspects of
      anterior pituitary response to stress have been poorly studied, available data
      suggest that dramatic changes occur in some hormones during weaning, with some,
      but less profound, change thereafter. Responsiveness to stressors appears to
      mature with age, but developmental patterns differ among the various anterior
      pituitary hormones.

PMID- 9785122
TI  - Responses to maternal separation: mechanisms and mediators.
AB  - Clinical studies indicate the predominance of psychosocial factors (nurturing
      environment) in the genesis of the Maternal Deprivation Syndrome. Consequences of
      disrupting mother-infant interactions range from marked suppression of certain
      neuroendocrine and physiological systems after short periods of maternal
      deprivation to retardation of growth and behavioral development after chronic
      periods. We have shown that maternal separation initiates a complex adaptive
      biobehavioral response in preweaning rat pups that includes (1) a decrease in the
      synthesis of ornithine decarboxylase, an obligatory enzyme for normal cell growth
      and development, (2) a reduction in DNA synthesis, an index of cell
      multiplication, (3) abnormal patterns of neuroendocrine secretion, and (4) a
      suppression of cell responses to growth hormone, prolactin and insulin, three
      major trophic hormones. This unique pattern of adaptation to maternal separation
      is not related to food or temperature changes but results from a lack of a
      specific type of tactile stimulation of the pup by the mother. Recently, we have
      shown that in the absence of "nurturing touch" the brain initiates the
      suppression of ornithine decarboxylase gene transcription by interfering with the
      cell's ability to transduce the activating signal induced by the growth promoting
      hormones. Studies indicate that central endorphinergic pathways may mediate this
      action. This is accomplished by the downregulation of specific Immediate Early
      Genes (c-myc and max) that normally promote the synthesis of this critical growth
      regulatory enzyme. These studies of short-term maternal separation not only
      demonstrated that maternal care is a critical regulator of pup physiology and
      biobehavioral development but that there are marked similarities between this
      animal model of maternal separation and the delay in growth and development
      observed in children with the deprivation syndrome or in touch-deprived premature
      human neonates. Our identification of a specific type of nurturing touch as a
      neonatal growth requirement led us to test supplemental tactile stimulation in
      isolated very-premature human babies. The result of our intervention with massage
      was dramatic. Infants not only showed marked gains in weight and behavioral
      development, but also a significant enhancement in sympatho-adrenal maturation.
      We suggest that animal models of maternal deprivation can be used to understand
      the integrative processing of appropriate sensory input, CNS function and end
      organ physiology required to maintain normal development.

PMID- 9785123
TI  - Developmental regulation of the brain polyamine-stress-response.
AB  - A transient increase in brain polyamine metabolism, termed the polyamine-stress
      response is a common response to stressful stimuli. Previous studies have
      implicated an over-reactive polyamine response as a component of the maladaptive
      brain response to stressful events, and as a novel molecular mechanism involved
      in the pathophysiology of affective disorders. Ample evidence indicates that
      stressful experiences during early life can alter normal developmental processes
      and may result in pathophysiological and behavioral changes in the adult.
      Additionally, an important characteristic of affective disorders is their age
      dependency, a phenomenon that may be correlated with a maladaptive regulation of
      the hypothalamic-pituitary-adrenocortical (HPA) neuroendocrine system. In the
      present study we measured the activities of the enzymes ornithine decarboxylase
      and S-adenosylmethionine decarboxylase as markers of polyamine synthesis and
      found that unlike adults, immature rats do not show the characteristic brain
      polyamine-stress-response. Instead of the characteristic increase observed in
      adults, ornithine decarboxylase activity in immature animals was reduced or
      remained unchanged (for up to 16 days of age) after a dexamethasone injection or
      restraint stress application. The ontogenesis of this ornithine decarboxylase
      response was brain region-specific, indicating its dependence on the stage of
      neuronal maturation. Animals treated with dexamethasone at 7 days of age, showed
      increased behavioral reactivity in the open-field test as adults and an
      attenuated increase in ornithine decarboxylase activity after a re-challenge with
      dexamethasone at age 60 days. The results indicate that: (1) the brain polyamine
      stress-response is developmentally regulated and its ontogenesis is brain region
      specific, indicating dependence on the stage of neuronal maturation; (2) the
      switch to a mature polyamine-stress-response pattern coincides with the cessation
      of the stress hyporesponsive period in the HPA system: (3) activation of the
      polyamine-stress-response, as in the mature brain, appears to be a constructive
      reaction, while its down-regulation, as in the developing brain, may be
      implicated in neuronal cell death; (4) an attenuated dexamethasone-induced
      increase in ornithine decarboxylase activity implicates an altered polyamine
      stress-response in the maladaptive response of the brain to stressful events.

PMID- 9785124
TI  - Gender- and age-dependent differences in latent inhibition following pre-weaning
      non-handling: implications for a neurodevelopmental animal model of
      schizophrenia.
AB  - Latent inhibition (LI) refers to retarded conditioning to a stimulus as a
      consequence of its prior nonreinforced pre-exposure, and is considered to index
      the capacity of an organism to ignore irrelevant stimuli. LI disruption has
      received increasing attention as an animal model of the widely described
      attentional deficit of schizophrenia, consisting of an inability to ignore
      irrelevant stimuli. The present experiments investigated the effects of infantile
      manipulations on the development of LI. Male and female rats handled or
      nonhandled in infancy (days 1-22), were tested at 3 and 16 months. Young handled
      animals had lower emotional reactivity than nonhandled, and this difference
      persisted in females at 16 months. At 3 months. LI, poorer conditioning of
      stimulus pre-exposed as compared to nonpre-exposed rats, was obtained in handled
      and nonhandled females, as well as in handled males, but was absent in nonhandled
      males. This pattern changed at 16 months: both nonhandled males and females
      failed to show LI. These gender- and age-dependent effects of pre-weaning
      manipulations on LI loss may provide an animal parallel to the susceptibility of
      young adult males to schizophrenia and the attenuation of gender differences in
      long-term outcome schizophrenia.

PMID- 9785125
TI  - Gender differences in sympathoadrenal activity in rats at rest and in response to
      footshock stress.
AB  - A comparison was made of the dynamics of sympathoadrenal activity in 11 age
      matched male and female rats, under basal conditions and after exposure to
      footshock. Rats were prepared with indwelling catheters in the tail artery 24 h
      before the experiment. Measurements were made of plasma corticosterone (COR),
      norepinephrine (NE), epinephrine (EPI), dihydroxyphenylalanine (DOPA),
      dihydroxyphenylglycol (DHPG) and dihydroxyphenylacetic acid (DOPAC) under resting
      conditions, after transfer to the shock box (novelty) and at various times after
      footshock. Under basal conditions, males have significantly higher blood pressure
      and plasma DHPG/NE ratios but lower plasma levels of COR, NE and DOPAC than
      females. Three min after exposure to the shock chamber (novelty stress) there
      were significant increases in COR, EPI, NE and DHPG in both sexes, while DOPA
      increased only in females and DOPAC remained unchanged in both sexes. Footshock
      produced a further increase in EPI, NE and DOPAC within 2 min, which lasted about
      15 min. There were significant sex differences in the extent and duration of the
      response of COR, EPI and DHPG. The data show that the female sympathoadrenal
      system is more reactive than that of the male to the stresses of a novel
      environment and footshock. The smaller DHPG/NE ratios in females at rest and
      after stress suggest that neuronal uptake of NE is lower in females than in
      males. The finding that stress produces larger increments of plasma DOPA and
      DOPAC in female rats indicates that tyrosine hydroxylase in the sympathetic nerve
      terminals and adrenal medulla may also be higher than in males.

PMID- 9785126
TI  - Stress and the adaptive self-organization of neuronal connectivity during early
      childhood.
AB  - A conceptual framework is proposed for a better understanding of the biological
      role of the stress-response and the relationship between stress and brain
      development. According to this concept environmental stimuli (in children mainly
      psychosocial challenges and demands) exert profound effects on neuronal
      connectivity through repeated or long-lasting changes in the release of
      especially such transmitters and hormones which contribute, as trophic,
      organizing signals, to the stabilization or destabilization of neuronal networks
      in the developing brain. The increased release of noradrenaline associated with
      the repeated short-lasting activation of the central stress-responsive systems in
      the course of the stress-reaction-process to psychosocial challenges which are
      felt to be controllable acts as a trigger for the stabilization and facilitation
      of those synaptic and neuronal pathways which are activated in the course of the
      cognitive, behavioral and emotional response to such stressors. The long-lasting
      activation of the central stress-responsive systems elicited by uncontrollable
      psychosocial conflicts in conjunction with the activation of glucocorticoid
      receptors by the sustained elevation of circulating glucocorticoid levels favors
      the destabilization of already established synaptic connections and neuronal
      pathways in associative cortical and limbic brain structures. The facilitation
      and stabilization of neuronal pathways triggered by the experience of
      controllable stress is thus opposed, attenuated or even reversed in the course of
      lon-lasting uncontrollable stress. This destabilization of previously established
      synaptic connections and neuronal pathways in cortical and limbic brain
      structures is a prerequisite for the acquisition of novel patterns of appraisal
      and coping and for the reorganization of the neuronal connectivity in the
      developing brain. Alternating experiences of repeated controllable stress and of
      long-lasting uncontrollable stress are therefore needed for the "self-adjustment"
      of neuronal connectivity and information processing the developing brain to
      changing environmental (psychosocial) demands during childhood. The brain
      structures and neuronal circuits involved in the regulation of behavioral
      responding become thus repeatedly reoptimized and refitted, not the changing
      conditions of life per se but rather to those conditions which are still able to
      activate the central stress responsive systems of an individual at a certain
      developmental stage.

PMID- 9785127
TI  - Perinatal characteristics and schizophrenia: electrodermal activity as a
      mediating link in a vulnerability-stress perspective.
AB  - Vulnerability-stress models of schizophrenia assert that the disorder results
      from an interaction between genetic or biologically acquired vulnerability and
      unfavourable environmental conditions. As our knowledge of early environmental
      factors for schizophrenia evolves, the question of links between early factors
      and a development of schizophrenia becomes more important. In this article, we
      analyse the relationship between obstetrical complications (OCs) and adult
      schizophrenia and methodological concerns in the search for pre- and perinatal
      risk factors. We review findings of aberrant electrodermal activity in
      schizophrenic patients and suggest that OCs may induce insults to cerebral
      structures that are critically involved in the control of orienting and of
      autonomic responses.

PMID- 9785128
TI  - Nodular hyperplasia, adenoma, and adenomyoma of Bartholin's gland.
AB  - Inflammatory lesions and cysts are by far the most common causes of swelling or
      enlargement of Bartholin's glands, and carcinomas, though rare, are the most
      frequent solid lesions that arise at this site. There have been very few reports
      of benign solid lesions of Bartholin's gland, and, among these lesions, the
      distinction between adenoma (AD) and hyperplasia has not been well defined. All
      cases diagnosed as either Bartholin's gland adenoma or hyperplasia in the Armed
      Forces Institute of Pathology files were reviewed. Using specific criteria, 17
      qualified as nodular hyperplasia (NH), 1 as AD, and 1 as adenomyoma (AM). Five
      NHs, the AD, and the AM were studied with immunohistochemical stains for estrogen
      receptor (ER), progesterone receptor (PR), MIB-1, and p53. The average age of the
      patients with NH was 35 years (range, 19 to 56). These lesions were solid or
      solid and cystic, had a mean maximal dimension of 2.3 cm, and were frequently
      thought to be Bartholin's cysts on clinical examination. Microscopically, the NHs
      had an irregular or lobulated contour and were composed of a proliferation of
      cytologically bland mucinous acini with maintenance of the normal duct-to-acinar
      relationship. Varying degrees of inflammation and squamous metaplasia of the
      ducts were common in NH. The patient with the AD was 45 years old and the patient
      with AM was 65. Both were well-circumscribed, solid lesions, 2.2 and 2.5 cm in
      maximal dimension, respectively, and composed of a haphazard proliferation of
      acini and tubules. A small adenoid cystic carcinoma (ACC) arose from the
      periphery of the AD. p53 positivity was evident in up to 40% of the ACC cells;
      the cells in the adjacent AD were negative for p53. Only occasional cells were
      MIB-1 positive (< 5%) in some cases, and ER and PR were absent in the epithelial
      elements in all 7 cases tested but were focally present in the stromal cells of 3
      of the 5 NHs and the fibromuscular stroma of the AM. The patient with the AM and
      the one with the AD are alive without evidence of recurrent or metastatic disease
      after 4 months and 19.8 years, respectively. NH, AD, and AM of the Bartholin's
      gland, as defined in this study, are extremely rare lesions. NH occurs in younger
      patients and is often associated with inflammation or obstruction of Bartholin's
      duct.

PMID- 9785129
TI  - Expression of metalloproteinases and their inhibitors in adenocarcinoma of the
      uterine cervix.
AB  - Metalloproteinases (MMPs), a family of enzymes that participate in extracellular
      matrix degradation and remodeling, may play a role in tumor invasion and
      metastasis and have been correlated with tumor behavior and survival. The action
      of MMPs is regulated by tissue inhibitors of MMPs (TIMPs). Adenocarcinomas of the
      uterine cervix are neoplasms that primarily affect young women and are associated
      with human papillomavirus (HPV). Eighteen cervical adenocarcinomas and 5 controls
      were immunohistochemically analyzed for the expression of MMP-2, MMP-3, MMP-9,
      and their inhibitors, TIMP-1 and TIMP-2, in tumor cells and peritumoral stromal
      cells. These cells were also studied for the presence of MMP-2, MMP-9, and TIMP-2
      mRNA by in situ hybridization (ISH). HPV status was studied using ISH for HPV 16
      and 18. MMP-2 and -9 were expressed immunohistochemically in tumor cells in 17 of
      18 tumors, MMP-3 in 5, TIMP-1 in 3, and TIMP-2 in 1. Stromal cells of most tumors
      expressed all the above proteins. The normal endocervical epithelium was
      uniformly negative for MMP-2, MMP-3, MMP-9, and TIMP-2, and variably expressed
      TIMP-1. Intense signals for MMP-2, MMP-9, and TIMP-2 mRNA were less frequently
      detected by ISH in tumor cells and peritumoral stromal cells and were absent in
      normal endocervical epithelium. All tumors contained HPV DNA 16, 18, or both. MMP
      and TIMP expression did not correlate with tumor type, grade, or HPV type. MMPs
      and their inhibitors are present in most cervical adenocarcinomas, independent of
      tumor grade or subtype, but with the exception of TIMP-1, they are not expressed
      in nonneoplastic endocervical epithelium. This finding might be helpful in the
      diagnosis of endocervical adenocarcinomas. HPV is prevalent in cervical
      adenocarcinomas, but its role in determining tumor behavior remains unclear.

PMID- 9785130
TI  - Endometrial polyps: a comparison study of patients receiving tamoxifen with two
      control groups.
AB  - Many reports describe an increased frequency and unusual features of endometrial
      polyps and carcinomas in women treated with tamoxifen (TMX) for breast cancer.
      Postmenopausal women with endometrial polyps were identified by computer search
      of pathology files from 1990 to 1996. Medical records were reviewed, and patients
      were divided into three groups: 28 receiving TMX for breast cancer, 23 receiving
      hormone replacement therapy (HRT), and 28 untreated controls (UC). Cumulative
      doses (CDs) of TMX were calculated. Histologic slides of polyps were reviewed
      blindly and evaluated for size, metaplasias, vascularity, fibrosis, and
      inflammation. Carcinomas were found in 3 TMX, no HRT, and 1 UC patient. Atypical
      hyperplasias were found in 1 TMX, 0 HRT, and 1 UC patient. Mean polyp size was
      larger in the TMX group (2.9 cm) than in the HRT (1.05 cm) and UC (1.35 cm)
      groups, and stromal fibrosis was more prominent in TMX-related and larger polyps.
      Mucinous metaplasias were observed more frequently in the patients receiving TMX.
      No other differences were noted. The two TMX patients in whom low-grade
      carcinomas developed and the one with atypical hyperplasia had independent risk
      factors. CDs for these patients were 32.9, 36.5, and 17.6 g, respectively. A high
      grade carcinoma developed in a TMX patient without constitutional risk factors at
      a CD of 94.9 g. On the basis of a literature review and these results, low-grade
      carcinomas developing after relatively low CDs of TMX may be at least partially
      attributable to other risk factors. The association between poorly differentiated
      and nonendometrioid tumors with higher TMX CDs is still speculative, but the
      current study suggests that they may be related to TMX. A statistically
      significant increase in the frequency of thyroid replacement use by TMX patients
      is also noted.

PMID- 9785131
TI  - DNA content is an independent prognostic indicator in endometrial adenocarcinoma.
      A Gynecologic Oncology Group study.
AB  - The identification of prognostic variables is an important aspect of managing and
      counseling women with endometrial adenocarcinoma. The surgical stage, age, cell
      type, depth of myometrial invasion, and histologic grade have all been previously
      demonstrated to be related to prognosis. Several reports have indicated that
      tumor ploidy as determined by flow cytometry with fresh or fixed cells removed
      from paraffin blocks of endometrial adenocarcinomas can contribute to the
      assessment of prognosis. To verify the significance of DNA content in endometrial
      adenocarcinoma, we conducted an historical cohort study on a subgroup of women
      from a Gynecologic Oncology Group (GOG) protocol of early clinical stage disease.
      Flow cytometry was performed at one facility on cells extracted from blocks
      obtained from several GOG member institutions. Blocks were submitted for 293 of
      933 eligible patients. Ninety-two histograms were of good quality, with 55
      interpreted as diploid and 37 as aneuploid. One hundred sixty-two histograms were
      technically suboptimal, of which 137 were considered probably diploid, 13
      probably aneuploid, and 12 unacceptable due to high background noise. Of the
      commonly accepted prognostic variables, only depth of invasion was significantly
      related to the ploidy status. There was no discernable difference in survival
      between patients with diploid and patients with probable diploid and probable
      aneuploid tumor types. Incorporation of the flow cytometry data into a
      proportional hazards regression model adjusted for age and surgical stage
      revealed a significant increased risk of disease-related death (relative risk,
      4.1; 95% confidence interval, 2.3 to 7.3) for patients with aneuploid tumor type
      as compared to patients with diploid tumor type. This study confirms the
      prognostic significance of ploidy determination by flow cytometry and also
      indicates some of the difficulties of retrospectively applying this technology to
      cooperative group studies.

PMID- 9785132
TI  - Cell proliferation-associated proteins in endometrial carcinomas, including
      papillary serous and endometrioid subtypes.
AB  - Cyclin dependent kinases (cdks) and cyclins regulate the progression of cells
      through the cell cycle and can be overexpressed in human cancers. The purpose of
      this study was to evaluate the immunohistochemical profile of these proliferation
      associated proteins and correlate the results with clinicopathologic parameters
      of endometrial carcinomas. Archival tissue sections from 91 endometrial
      carcinomas were immunostained using monoclonal antibodies against p34CDC2 cdk,
      cyclins A and B1, p120, Ki-67, and PCNA. Immunoreactivity was semiquantitatively
      assessed and the results correlated with pathologic features and survival. Of the
      91 endometrial carcinomas, 74 were endometrioid (17 villoglandular, 57 of usual
      type) and 17 were papillary serous carcinomas. The positivity rates for the
      different proteins in papillary serous and endometrioid tumors, respectively,
      were as follows: p34CDC2, 24% and 23%; cyclin A, 71% and 64%; cyclin B1, 24% and
      26%; p120, 47% and 9%; Ki-67, 82% and 64%; and PCNA, 47% and 47%. Only p120
      correlated with histologic tumor type with significantly higher expression in
      both papillary serous and villoglandular endometrioid carcinomas compared to
      nonvilloglandular endometrioid carcinomas (p = 0.0001). p120 positivity also
      correlated with advanced tumor stage (p = 0.0001). Ki-67, cyclin A, and PCNA
      correlated with patient survival in endometrioid carcinomas on univariate
      analysis (p = 0.01, 0.02, and 0.003, respectively), but, on multivariate
      analysis, only tumor grade (p = 0.02) and depth of invasion (p = 0.04) were
      independent predictors of outcome. In summary, although most of the cell
      proliferation-associated proteins studied did not appear to be associated with
      clinicopathologic features of endometrial carcinoma, there was significantly
      higher expression of p120 in papillary serous and villoglandular endometrioid
      carcinomas compared to nonvilloglandular endometrioid carcinomas, suggesting a
      possible role of p120 in tumor behavior. In addition, Ki-67, cyclin A, and PCNA
      expression correlated with survival in endometrioid carcinoma, but only in a
      univariate analysis.

PMID- 9785133
TI  - Endometrial adenocarcinoma associated with intrauterine pregnancy. A report of
      five cases and a review of the literature.
AB  - Endometrial adenocarcinoma associated with pregnancy is a rare lesion; only 14
      acceptable examples have been reported in the literature. This study describes
      five additional examples with a critical review of the previously published
      cases. Four of the five women were nulliparous and three had sought medical
      intervention for infertility. The tumors were all well-differentiated
      endometrioid adenocarcinomas; three had a focal to extensive papillary pattern
      and three had focal to extensive squamous differentiation. Four were diagnosed at
      the time of dilatation and curettage and one at the time of cesarean section for
      a 28-week, live infant. Follow-up was available for four of the five women. Two
      women underwent hysterectomy with bilateral oophorectomy and were alive and well
      12 and 48 months after diagnosis. The woman who had the live birth and the
      remaining woman were treated by repeat curettage with or without progesterone
      therapy, and each woman has had two subsequent full-term pregnancies with live
      births. These women are alive and well 57 and 58 months after diagnosis. Women
      with focal, well-differentiated carcinomas can successfully maintain their
      fertility if followed by repeat curettage with or without progesterone therapy.

PMID- 9785134
TI  - Mast cells in smooth muscle tumors of the uterus.
AB  - Mast cells (MCs) have been reported in the myometrium and uterine smooth muscle
      tumors. We examined the number of MCs in various uterine smooth muscle tumors
      (including leiomyosarcomas) and assessed whether this feature might be of value
      in their pathologic diagnosis. The number of MCs in 95 uterine smooth muscle
      tumors, including 55 ordinary leiomyomas, 17 cellular leiomyomas, 8 bizarre
      leiomyomas, and 15 leiomyosarcomas, was counted using toluidine blue and
      immunohistochemical staining. The number of MCs that stained for tryptase was
      lowest in leiomyosarcoma and next lowest in ordinary leiomyoma; the number in
      each of these two groups was significantly lower than in the myometrium (p <
      0.001). In cellular and bizarre leiomyomas, the number of MCs was significantly
      higher than in ordinary leiomyoma (p < 0.001 and p < 0.001, respectively) and
      leiomyosarcoma (p < 0.001 and p < 0.005, respectively). Statistical analysis
      revealed that counting the number of MCs and using a cut-off value of 16 MCs per
      high-power-field is useful for the differential diagnosis of leiomyosarcomas from
      cellular leiomyoma and bizarre leiomyoma, yielding 100% sensitivity and 96%
      specificity. The number of MCs was significantly lower in leiomyosarcomas at TNM
      stages III and IV than in those at stages I and II (p < 0.05), but there was no
      significant correlation between the number of MCs and patient survival. These
      results suggest that the number of MCs might be useful as part of a multivariate
      approach to the differential diagnosis of leiomyosarcoma from bizarre or cellular
      leiomyoma.

PMID- 9785136
TI  - Ovarian mature cystic teratoma with malignant transformation. An interphase
      cytogenetic study.
AB  - The chromosomal composition of cancers arising in ovarian mature cystic teratoma
      (MCT) was analyzed using chromosome in situ hybridization (CISH) performed on
      paraffin-embedded material from 10 squamous cell carcinomas, 1 adenocarcinoma, 1
      thyroid papillary carcinoma, and 1 strumal carcinoid. Cervical tissue from seven
      of these patients was used as a control. In the cancers, a relative gain of
      chromosome 16 (in 7 cases), chromosome 12 (in 9), chromosome 11 (in 10), and
      chromosome X (in 8) was detected. Trisomy 12 was diagnosed in eight cases. No
      chromosomal aberrations were detected in the strumal carcinoid. In the benign
      areas of the MCTs, only one case showed a gain of chromosome 11, although, in
      another case, there was a gain of chromosome X. Malignant transformation of MCTs
      often occurs in association with complex chromosome aberrations that may play a
      role in the development of such carcinomas.

PMID- 9785135
TI  - Immunohistochemical detection of Listeria antigens in the placenta in perinatal
      listeriosis.
AB  - Listeria monocytogenes, a worldwide pathogen, causes significant perinatal
      mortality and morbidity and has been implicated in spontaneous abortions, still
      births, premature delivery, and neonatal sepsis, often with meningitis. Maternal
      symptoms are frequently minimal, and diagnosis is made only if the suspicion is
      high and diagnostic maternal blood or amniotic fluid cultures are performed.
      Because cultures are not routinely performed on spontaneously aborted fetuses,
      many authors feel that the true incidence of the disease may be underestimated.
      To date, the absence of a test to retrospectively diagnose Listeria infection has
      contributed to the lack of accurate estimates of the incidence of the disease.
      Seven cases in which immunohistochemical stains were used to confirm the
      diagnosis of placental listeriosis are described. All placentas showed the
      characteristic lesions with severe chorioamnionitis, numerous microabscesses, and
      focal necrotizing villitis. Immunohistochemical localization of Listeria antigen
      was made to the amnion (focally in areas with no inflammatory infiltrate), the
      abscesses, and the areas with villitis. In general, the antigen was extracellular
      and intracellular, predominantly within macrophages or the amnion epithelium.
      Listeria antigen was often found where definite identification of the organism
      was not possible on Brown-Hopps or Warthin-Starry stains. The immunohistochemical
      technique may therefore show an increase in sensitivity of detection of L
      monocytogenes compared with routine bacterial stains. Moreover, the ability to
      retrospectively evaluate placental specimens for evidence of this organism should
      permit the true incidence of perinatal listeriosis to be determined.

PMID- 9785137
TI  - Liesegang rings and endometriosis.
AB  - Liesegang rings (LRs) are acellular, ringlike structures that may from within and
      around inflamed or necrotic tissue. LRs are most commonly found within the
      kidneys, synovium, and eyelid and in association with pelvic inflammatory disease
      and other infectious processes. LRs are only rarely found within the female
      genital tract, usually within endometriotic cysts or around areas of chronic
      inflammation. Three additional patients with LRs associated with endometriosis
      are described. In one of them, LRs occurred at the edge of an endometriotic cyst
      adjacent to a well-differentiated endometrioid adenocarcinoma of the ovary. All
      cases were characterized by the presence of multiple eosinophilic, sharply
      demarcated ringlike structures that were highlighted by the periodic acid-Schiff
      method. LRs within the female genital tract, which appear to be closely related
      to endometriosis, should be distinguished from both benign or malignant
      processes.

PMID- 9785138
TI  - Goblet-cell mucinous epithelium lining the endometrium and endocervix: evidence
      of metastasis from an appendiceal primary tumor through the use of cytokeratin-7
      and -20 immunostains.
AB  - Differential staining with cytokeratin (CK)-7 and CK-20, two members of a complex
      family of proteins in human epithelial cells, proved critical in showing that the
      extremely well-differentiated goblet-cell (intestinal) mucinous epithelium lining
      the surface of the endometrium and endocervix in two patients and the fallopian
      tube in one was identical to that of the coincident appendiceal neoplasms. One of
      these patients also had a large ovarian tumor that grossly and microscopically
      resembled a mucinous cystadenoma of borderline malignancy and would have been
      considered primary except for the CK stains (CK-20 positive and CK-7 negative),
      which suggested metastasis from the appendix, presumably by a transtubal route.

PMID- 9785139
TI  - Localized amyloidosis of the uterine cervix.
AB  - Localized amyloidosis of the uterine cervix is a rare entity. Only seven cases
      have been reported to date, and all were associated with a primary cervical
      squamous cell carcinoma; immunohistochemical studies proved the amyloid to be
      composed of cytokeratin, presumably derived from degenerated tumor cells. We
      report localized cervical amyloidosis producing a 1-cm nodule in a 28-year-old
      woman in the absence of systemic amyloidosis or a squamous cell carcinoma.
      Immunohistochemical stains showed the amyloid to be composed of amyloid
      associated protein, a protein produced in chronic inflammatory conditions.

PMID- 9785140
TI  - Papillary squamotransitional cell carcinoma of the vagina.
AB  - A case of papillary squamotransitional carcinoma of the vagina is reported. The
      immunohistochemical profiles (cytokeratin-7 and -20) and the detection of human
      papillomavirus 16 support its close relationship to conventional squamous cell
      carcinoma. The lesion is compared to previously reported cases of papillary
      transitional cell carcinoma of the vagina and papillary squamotransitional cell
      carcinoma of the cervix.

PMID- 9785141
TI  - Primary uterine T-cell lymphoma.
AB  - A uterine CD8-positive, HTLV-1-negative T-cell lymphoma associated with atypical
      endometrial hyperplasia was found in a 63-year-old Japanese woman. Primary T-cell
      lymphoma of the uterus has not been previously reported.

PMID- 9785142
TI  - History of gynecological pathology. V. Dr. Walter Schiller.

PMID- 9785143
TI  - Recurrent serous borderline tumors of the ovary.

PMID- 9785144
TI  - Donepezil for treatment of dementia with Lewy bodies: a case series of nine
      patients.
AB  - Dementia with Lewy bodies (DLB) is common. Symptomatic treatment can be
      difficult. We reviewed nine consecutive patients with DLB (mean age 77.5 [range
      67 to 84] years; seven men and two women; mean duration of disease 3.7 [range 1.5
      to 8.0] years) who had been treated with donepezil. Each initially received 2.5
      to 5 mg per day of donepezil, and was stabilized on 5 mg per day. Donepezil was
      increased to 10 mg per day in five patients. The mean observation period was 12
      (range 8 to 24) weeks. Target symptoms included cognition, hallucinations,
      parkinsonism, and functional abilities. By both cognitive testing and family
      reports, cognition improved in seven of nine patients, remained the same in one
      of nine, and fluctuated in one of nine (mean Mini-Mental State Examination change
      4.4 +/- 6.3 points). Function was improved or maintained in six of nine patients
      and fluctuated in two of nine. Hallucinations initially worsened, then fluctuated
      in one patient, but improvement in frequency, duration, and content was reported
      in eight of nine cases. In three of nine patients, treatment with donepezil
      resulted in worsening of parkinsonism, which in each case responded to
      levodopa/carbidopa. Treatment of DLB patients with donepezil for 12 weeks most
      commonly improved hallucinations, and sometimes improved cognition and overall
      function. Treatment with donepezil was sometimes associated with worse
      parkinsonism.

PMID- 9785145
TI  - Behavioral disturbances and pharmacological treatment of patients with dementia
      in family caregiving: a 2-year follow-up.
AB  - Behavioral disturbances are common in dementia. Polypharmacy due to progression
      of disease and fluctuation of symptoms among patients might increase risk of
      overtreatment and/or undertreatment. Drug prescription habits were studied in
      relationship to symptoms of dementia after relocation of patients to group-living
      care units (GC). Seventy-six demented patients (mean age 81 years) were assessed
      before, 12 months after, and 24 months after relocation to GC. Vascular dementia
      was found in 47%, Alzheimer's dementia in 46%, and other dementias in 7%.
      Medications, regular or as required, were recorded from medication lists.
      Repeated observations of symptoms like depressive mood and lack of vitality were
      made with validated scales. Eighty percent of the patients were prescribed drugs;
      40% were given neuroleptics and 9% were given antidepressants. During the 2-year
      follow-up, polypharmacy increased; patients with five drugs or more increased
      from 15% to 35%; usage of neuroleptics or sedatives, as required, increased from
      8% to 25%, p < .01. Depressive mood was noted in 86% after 2 years and 74% showed
      aggressiveness and anxiety, but only 12% of the patients with depressive symptoms
      were on antidepressants. Analgesics were prescribed to 26% of patients. In
      conclusion, a high proportion of patients with dementia had depressive mood and
      undertreatment of depressive disorder might be suspected. Polypharmacy increased
      during the 2-year follow-up; this finding calls for careful monitoring of adverse
      drug reactions, because of the deteriorating cognitive function of these
      patients.

PMID- 9785146
TI  - Getting lost in dementia: a longitudinal study of a behavioral symptom.
AB  - The occurrence of episodes of getting lost was examined in 104 subjects with
      dementia who were assessed every 4 months over 5 years. All subjects were
      initially living at home with a caregiver who could give good information. Forty
      three subjects needed to be brought back home at least once. Five subjects
      repeatedly got lost. Forty-six subjects were kept behind locked doors at some
      point. Subjects who got lost were more likely to become permanently resident in
      institutions (odds ratio = 7.3; 95% confidence interval: 3.0 to 17.8). Patients
      who performed better on a behavioral test of topographical memory were less
      likely to get lost over the subsequent 5 years (negative predictive value: 90%).
      The risk of patients with dementia getting lost is substantial and requires
      frequent intervention by caregivers. This risk is a major reason for
      institutionalization. A simple test may help in assessing the risk of getting
      lost in patients with dementia.

PMID- 9785147
TI  - Clinical validity and utility of the interview for deterioration of daily living
      in dementia for Spanish-speaking communities NORMACODEM Group.
AB  - The assessment of activities of daily living is a central procedure in the
      diagnosis of dementia. Few instruments in the field allow for early detection of
      functional decline because the items they use refer mainly to basic activities of
      daily living (BADL), which do not become compromised until later in the disease
      process. The Interview for Deterioration of Daily Living in Dementia (IDDD) may
      be a valuable tool for early detection of functional decline because it includes,
      apart from a BADL subscale, another subscale containing a variety of instrumental
      activities of daily living (LADL), which are the first to be affected in
      dementing processes. We present an adaptation and validation of the IDDD for
      Spanish-speaking communities (S-IDDD). A total of 254 control subjects (CONT), 86
      patients with mild memory/cognitive impairment with no dementia (CIND), and 111
      patients diagnosed with probable dementia of the Alzheimer type (DAT)
      participated in this project. IDDD total scores (mean and SD) were as follow:
      CONT: 33.1 (0.4); CIND: 35.2 (3.4); DAT: 54.3 (18.6). The present validation
      showed no sociodemographic effects on the IDDD total scores. The IDDD
      demonstrated great internal consistency (alpha = .985) and reproducibility
      (intraclass correlation coefficient = .94). Correlations were high (r = .81; p <
      .1) when they took into account the whole sample, but decreased significantly
      when the groups were separated by pathologic condition. The scale showed
      significant differences between DAT versus CIND and CONT. The IADL subscale
      differentiated all three groups, which makes it extremely valuable for early
      detection of functional decline. The present study shows that the S-IDDD is a
      reliable adaptation of the original IDDD scale and may be used successfully in
      Spanish populations for staging and follow-up of subjects with dementia.

PMID- 9785148
TI  - Accurate prediction of histologically confirmed Alzheimer's disease and the
      differential diagnosis of dementia: the use of NINCDS-ADRDA and DSM-III-R
      criteria, SPECT, X-ray CT, and Apo E4 in medial temporal lobe dementias. Oxford
      Project to Investigate Memory and Aging.
AB  - In a prospective study of more than 200 cases of dementia and 119 controls,
      annual technetium-99m-hexamethyl-propylene amineoxime (99mTC-HMPAO) single-photon
      emission computed tomography (SPECT) and annual medial temporal lobe (MTL)
      oriented X-ray computed tomography (CT) have been used to evaluate the diagnostic
      potential of functional and structural neuroimaging in the differential diagnosis
      of dementia. Some subjects have had up to 7 annual evaluations. So far, of 151
      who have died, 143 (95%) have come to necropsy. Histology is known for 118, of
      whom 80 had Alzheimer's disease (AD), 24 had other "non-AD" dementias, and 14
      controls with no cognitive deficit in life also had no significant central
      nervous system pathology. To compare the findings in the dementias with the
      profile of structural and functional imaging in the cognitively normal elderly,
      scan data from 105 living, elderly controls without cognitive deficit have also
      been included in the analysis. All clinical diagnoses were according to National
      Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's
      Disease and Related Disorders Association (NINCDS-ADRDA) and the Diagnostic and
      Statistical Manual of Mental Disorders (3rd ed., rev.; DSM-III-R) criteria, and
      all histopathological diagnoses according to the Consortium to Establish a
      Registry for Alzheimer's Disease (CERAD) criteria. Early data from this cohort
      have suggested that the combination of both MTL atrophy seen on CT with
      parietotemporal hypoperfusion on SPECT may predict the pathology of AD. The
      diagnostic sensitivity, specificity, accuracy, and positive and negative
      predictive values of the NINCDS-ADRDA and DSM-III-R criteria could be assessed in
      this cohort against the gold standard of histopathology. The diagnostic potential
      of CT evidence of MTL atrophy alone, SPECT evidence of parietotemporal
      hypoperfusion alone, and the combination of both of these scan changes in the
      same individual could then be compared against the diagnostic accuracy of
      clinical operational criteria in the pathologically confirmed cases. Furthermore,
      all of these modalities could be compared with the diagnostic accuracy of
      apolipoprotein E4 (Apo E4) genotyping to predict AD in the histopathologically
      confirmed cohort. In this population, NINCDS "probable-AD" was 100% specific, 49%
      sensitive, and 66% accurate; "possible-AD" was only 61% specific, but 93%
      sensitive and 77% accurate; and the combination of both "probable-AD" and
      "possible-AD" was 61% specific, 96% sensitive, and 85% accurate. DSM-III-R
      criteria were 51% sensitive, 97% specific, and 66% accurate. In the same cases
      and including the 105 living, elderly controls, the diagnostic accuracy of the
      Oxford Project to Investigate Memory and Aging (OPTIMA) scanning criteria showed
      CT alone to be 85% sensitive, 78% specific, and 80% accurate; SPECT alone had 89%
      sensitivity, 80% specificity, and 83% accuracy; and the combination of the two
      was 80% sensitive, 93% specific, and 88% accurate. The Apo E4 genotype was 74%
      sensitive but yielded 40% false positives in the histologically confirmed series.
      The diagnostic accuracy afforded by this method of CT and SPECT used alone is
      better than that of any established clinical criteria and reveals that the
      combination of MTL atrophy and parietotemporal hypoperfusion is common in AD,
      much less common in other dementias, and rare in normal controls. In the NINCDS
      ADRDA criteria "possible-AD" cases, the combination of CT and SPECT findings
      alone were better in all diagnostic indices than the presence of Apo E4 alone in
      predicting AD. The frequent occurrence of MTL atrophy in AD and also in other
      "non-AD" dementias later in the course of the disease suggests the concept of
      medial temporal lobe dementia. This could explain some of the overlap of clinical
      profiles in the dementias, particularly as the dementia progresses, making
      clinical differential diagnosis difficult. In this context, the use of SPECT can
      significantl

PMID- 9785149
TI  - Detection and diagnosis of delirium in the elderly: psychiatrist diagnosis,
      confusion assessment method, or consensus diagnosis?
AB  - The clinical diagnosis of delirium has traditionally been based on an assessment
      by one or more physicians. Because of the transient, ubiquitous, and fluctuating
      nature of the symptoms of delirium, however, this approach may be flawed.
      Therefore, we decided to compare diagnosis based on one assessment by a
      psychiatrist, diagnosis by a nurse clinician (using the Confusion Assessment
      Method [CAM] and multiple observation points), and diagnosis by consensus. The
      study subjects were 87 patients aged 65 and over who were admitted consecutively
      from the emergency department to the medical wards, and who scored 3 or more on
      the Short Portable Mental Status Questionnaire. All subjects were assessed
      independently by one of three psychiatrists (a chart review and clinical
      examination) and a nurse clinician (using the CAM and multiple observation
      points). A consensus conference, attended by the three psychiatrists and the
      nurse clinician, used all available information to reach a consensus diagnosis.
      Compared to the consensus diagnosis, the clinical diagnosis by a psychiatrist had
      a sensitivity of .73 (95% confidence interval [CI]: .61-.85), a specificity of
      .93 (95% CI: .79-1.0), and an agreement kappa coefficient of .58 (95% CI: .41
      .74). The nurse clinician diagnosis had a sensitivity of .89 (95% CI: .81-.97), a
      specificity of 1.00, and an agreement kappa coefficient of .86 (95% CI: .75-.97).
      These results suggest that one clinical assessment by a psychiatrist may not be
      the best method for detecting and diagnosing delirium in the elderly. A consensus
      diagnosis or diagnosis by a trained rater (using the CAM and multiple observation
      points) may be more sensitive approaches.

PMID- 9785150
TI  - Alcohol use disorder is a risk factor for mortality among older public housing
      residents.
AB  - Epidemiologic survey data were used to examine relationships between alcohol use
      and abuse and the physical and mental health status of elderly public housing
      residents (weighted n = 865) and to determine the influence that drinking
      behavior had on mortality. Residents with a current alcohol disorder (4%) were
      more likely to rate their physical health as fair/poor but had fewer major
      medical illnesses, functional impairments, and other current psychiatric
      disorders. Individuals with a current or past alcohol disorder (22%) were more
      likely than others to die (odds ratio [OR] = 7.5) during the 28-month follow-up
      period. In multivariate analyses, women with a past alcohol disorder were more
      likely than lifetime abstainers to die (OR = 21.9). Drinking behavior was not
      predictive of death in men. The high prevalence of alcohol disorder and its
      strong influence on mortality in this predominantly African-American female
      population demonstrate the need for programs designed to prevent and treat
      alcoholism in public housing developments for the elderly.

PMID- 9785151
TI  - Depression in elderly spouse pairs.
AB  - OBJECTIVE: This study aimed to investigate the prevalence of depression in aged
      spouse pairs and the associations between the occurrence of depression in one
      spouse (respondent) and the variables representing the respondent himself/herself
      and his/her partner. METHOD: Elderly (65 years or older) male (N = 176) and
      female (N = 176) spouses who constituted married couples that had participated in
      the epidemiological study on depression in old age conducted in Ahtari, Finland,
      in 1989-1990 made up the study series. The data were collected by postal
      questionnaires, interviews, and clinical investigations. Depression was
      determined according to the DSM-III criteria. RESULTS: Both husband and wife were
      depressed in 5.7% of the married couples. The husband was depressed and the wife
      was nondepressed in 10.2% of the couples; and the wife was depressed and the
      husband nondepressed in 10.8% of the couples. Among male respondents, poor
      physical health of the respondent, poor marital or family relations felt by the
      respondent, poor family relations felt by the marital partner, and a loss of the
      father by the marital partner while the partner was under 20 years of age were
      independently related to depression. Lowered functional abilities of the
      respondent was the only factor independently associated with the occurrence of
      depression in female respondents. CONCLUSIONS: The coexistence of depression in
      both elderly spouses is not uncommon. The results also give some evidence to
      suggest that the vulnerability for the development of depression in the wives may
      have some effects on the development of depression in elderly men.

PMID- 9785152
TI  - Outpatient management of deep vein thrombosis.
AB  - OBJECTIVE: To assess whether patients with deep vein thrombosis (DVT) could be
      satisfactorily treated on an outpatient basis with low molecular weight (LMW)
      heparin and warfarin. DESIGN: A 22 month prospective study of adults attending St
      Peter's Hospital accident and emergency department with DVT. RESULTS: 1093
      patients were referred and assessed; 160 were venogram positive, of which 159
      patients between the ages of 22 and 89 years of age have now been treated with
      LMW heparin as outpatients. Direct liaison with community nurses has minimised
      the impact on general practitioner workload. CONCLUSIONS: 1272 bed days were
      saved during this period (an estimated 320,000 pounds). The outpatient treatment
      of thromboembolism has been shown to be effective and safe.

PMID- 9785153
TI  - Computed tomography of the head by the accident and emergency department--why 24
      hour access is vital.
AB  - OBJECTIVE: To examine the use made of 24 hour access to computed tomography from
      an accident and emergency (A&E) department and to assess whether clear benefits
      for patients could be identified by having such a service. METHODS: Retrospective
      review of 176 cases where computed tomography was ordered by A&E staff of a large
      teaching hospital over a one year period. RESULTS: 53% of scans were done "out of
      hours"; 97% of scans performed (171/176) were studies of the brain. Three
      examinations were of the cervical spine and two were of the chest. 54% of head
      scans (93/171) were performed for either confirmed or suspected trauma with 46%
      (78/171) done for medical indications. Only 16% (11/71) of patients who had a
      head scan for acute trauma required transfer to the regional neurosurgical unit
      after consultation. Computed tomography was 100% sensitive in the diagnosis of
      sub-arachnoid haemorrhage. In cases where computed tomography was performed for
      coma of undetermined origin the pathology causing coma was identified on computed
      tomography in 50% of cases. CONCLUSIONS: Computed tomography facilities allow
      comprehensive initial evaluation of the head injured patient and minimise
      hazardous and expensive transfer of these seriously ill patients. Experience
      shows that it is a vital tool in the initial differential diagnosis of the
      comatose patient and therefore must be available for use by senior and middle
      grade A&E staff on a 24 hour basis.

PMID- 9785154
TI  - Avoidable deficiencies in the delivery of health care to children with
      meningococcal disease.
AB  - OBJECTIVES: It is apparent that delays and inadequate or inappropriate management
      occur frequently and may contribute to the continued high mortality seen in
      meningococcal disease. An attempt has been made to define the major sources of
      delay or inappropriate treatment. METHODS: A prospective, descriptive study of
      children with meningococcal disease referred to a tertiary centre paediatric
      intensive care and infectious disease unit. Definitions of optimal care were
      established at three stages: parental; general practitioner (GP)/accident and
      emergency (A&E) department; and hospital. Duration of symptoms and management
      were recorded from direct questioning of parents and carers, and from hospital
      records. RESULTS: 54 consecutive children with meningococcal disease were
      recruited to the study. Delayed parental recognition occurred in 16 children. GPs
      correctly diagnosed 19 of 35 children. Delay of 2.5-21 hours occurred in those
      who were incorrectly diagnosed. Two of 15 children who presented to the A&E
      department with specific features were incorrectly diagnosed. Hospital treatment
      was suboptimal in 71%. Shock was not recognised or treated in 50%, 20% of
      children had unnecessary lumbar punctures. Time from illness onset to treatment
      was longer in fatal disease (median 18.3, range 8-24 hours), compared with
      survivors (median 12, range 2-48 hours; p < 0.01, Mann-Whitney U test).
      CONCLUSION: Suboptimal treatment in meningococcal disease is due to failure of
      parents, GPs, and hospital doctors to recognise specific features of the illness.
      Improvement by public education and better training of clinicians in recognition,
      resuscitation, and stabilisation of seriously ill children.

PMID- 9785155
TI  - Non-invasive assessment of cardiac output in children.
AB  - BACKGROUND: Stroke distance, the systolic velocity integral of aortic blood flow,
      is a linear analogue of stroke volume; its product with heart rate is minute
      distance, analogous to cardiac output. OBJECTIVE: To investigate the feasibility
      of assessing cardiac output in children with a simple non-invasive Doppler
      ultrasound technique, and to determine the normal range of values. METHODS: Peak
      aortic blood velocity, stroke distance, and minute distance were measured through
      the suprasternal window in 166 children (mean age 9.6 years, range 2-14) using a
      portable non-imaging Doppler ultrasound instrument. RESULTS: The technique was
      well tolerated by all the children participating. Mean peak aortic blood velocity
      was 138 cm/s and was independent of age. Mean stroke distance was 31.8 cm and
      showed a small but significant increase with age; mean minute distance was 2490
      cm and fell with age, as did heart rate. CONCLUSIONS: Suprasternal Doppler
      ultrasound measurement of stroke distance is a convenient, well tolerated, non
      invasive technique for the assessment of cardiac output in children. The normal
      range of values during childhood has been established. The technique has great
      potential for assessing hypovolaemia in children.

PMID- 9785156
TI  - Emergency intubation of infants: does laryngoscope blade design make any
      difference?
AB  - OBJECTIVE: To compare intubation times and ease of use for a range of infant
      laryngoscope blades in the hands of accident and emergency (A&E) personnel.
      METHODS: Seven different blades were compared in terms of intubation times and
      ease of use scores in the hands of 30 A&E senior house officers (SHOs) and nurses
      using a standard infant manikin. RESULTS: There was a significant difference in
      intubation times between the seven blades (p < 0.001). Intubation with two blade
      designs (Seward and Soper) took almost twice as long as for the other blades (p <
      0.05). Subjective ease of use scoring also identified the Seward and Soper blades
      as being the most difficult to use (p < 0.05). There were no significant
      differences between SHO and nurse intubation times or ease of use scoring.
      Successful intubation was achieved within 30 seconds in 90% of attempts. All but
      two of the subjects used an incorrect levering technique for intubation despite
      all having previously received training in infant intubation. CONCLUSIONS: No
      current standard exists regarding the utilisation of infant laryngoscope blades
      in the A&E department. The first line blade available should be a C shaped blade
      (Miller, Oxford, Robert-shaw, or Wisconsin). Other blade designs should be kept
      for use only by more experienced personnel or in difficult intubation situations.
      Intubation training must focus on correct technique and regular assessment is
      essential.

PMID- 9785157
TI  - Can x rays be accurately interpreted using a low cost telemedicine system?
AB  - OBJECTIVE: To assess whether the quality of x ray films transmitted via a low
      cost (low resolution) telemedicine link was satisfactory for clinical diagnosis.
      METHODS: A retrospective study of a set of consecutive accident and emergency
      (A&E) radiographs. An A&E registrar viewed these directly on a standard x ray
      viewing box and via a telemedicine link. RESULTS: There were 81 abnormalities out
      of 234 x ray films. Three abnormalities were missed both on the x ray viewing box
      and telemedicine link, one of which was significant. There were five additional
      abnormalities missed on the telemedicine link but detected on the x ray viewing
      box, of which two were significant. One normal x ray film was interpreted as
      abnormal on the telemedicine link. There were no false positives on direct
      viewing. CONCLUSION: Transference of plain radiographs using a low cost/low
      resolution telemedicine link by A&E doctors is adequate for clinical
      interpretation.

PMID- 9785158
TI  - Use of the Ottawa ankle rules by nurse practitioners.
AB  - OBJECTIVE: To determine the ability of nurse practitioners to use the Ottawa
      ankle rules by comparing their requests for radiography with those of senior
      house officers (SHOs). METHOD: 1365 patients were assessed by a nurse trained in
      the use of the Ottawa ankle rules. Where indicated the nurse sent the patient for
      radiography. 700 patients in the same period were seen by SHOs who had not
      received training in these rules. After three months the SHOs were similarly
      trained in the use of the rules and a further 700 patients were seen. RESULTS:
      Nurse practitioners assessed 1365 patients; 72.6% had radiography. 1398 patients
      were seen only by an SHO. Before their use of the Ottawa ankle rules SHOs
      requested radiography in 91.0% (p = 0.001); using the rules this fell to 74.2% (p
      = 0.001). CONCLUSION: Nurse practitioners trained to use the Ottawa ankle rules
      are as effective as SHOs in the implementation of the rules. Moreover the
      sensitivity and specificity of the Ottawa ankle rules was similar to that seen in
      other studies.

PMID- 9785159
TI  - British Thoracic Society guidelines for the management of spontaneous
      pneumothorax: do we comply with them and do they work?
AB  - OBJECTIVES: To determine how British Thoracic Society (BTS) guidelines for the
      management of spontaneous pneumothorax have been implemented over a four year
      period in a large district general hospital with a specialised respiratory unit.
      To assess the validity of the guidelines in the management of spontaneous
      pneumothorax. METHODS: A retrospective case notes study over a four year period
      for all patients with spontaneous pneumothoraces attending the accident and
      emergency (A&E) department of a large district general hospital. RESULTS: 115
      episodes of spontaneous pneumothorax were identified. Overall 20.8% of episodes
      were treated correctly by BTS guidelines. Decisions made by A&E staff were
      significantly more likely to be correct than decisions made by on call medical
      teams (39.4% v 13.4%, p = 0.002). There was a non-significant trend towards
      better compliance with BTS guidelines over the four year period. The management
      decision was made by A&E staff only in 28.7% of episodes. Patients without
      chronic lung disease could be safely observed as outpatients. Forty three
      pneumothoraces were aspirated: 23 (58%) successfully; eight (18.6%) with little
      or no improvement; and 12 (27.9%) initially successfully but developing increased
      size of pneumothorax within a period of 72 hours. Three patients had repeat
      aspirations, two successfully. Age over 50, chronic lung disease, and more than
      2.5 litres of air aspirated were significantly associated with failure of
      aspiration (p < 0.01). There was a 28.6% failure rate of aspiration for patients
      with moderate pneumothoraces without chronic lung disease. CONCLUSIONS: Patients
      over the age of 50 should be treated the same as patients with chronic lung
      disease. A second aspiration should be attempted if the first aspiration is
      initially successful with subsequent recurrence of pneumothorax. Further research
      is required to clarify if patients with moderate pneumothoraces under the age of
      50 and no chronic lung disease should be aspirated or observed.

PMID- 9785160
TI  - "Saturday night fever": ecstasy related problems in a London accident and
      emergency department.
AB  - OBJECTIVES: To report on the extent and nature of acute MDMA (ecstasy) related
      problems presenting to a large London hospital's accident and emergency (A&E)
      department. METHOD: The computerised attendance records for all patients
      attending the A&E department over a 15 month period were retrospectively
      screened. Potential cases thus identified had their case notes systematically
      reviewed to confirm the history of MDMA use and to extract other relevant data.
      RESULTS: Forty eight consecutive MDMA related cases were identified. All were in
      the 15-30 year age group with the majority presenting in the early hours at
      weekends and having consumed the drug at a night club. The mean number of tablets
      consumed was two and almost 40% had taken MDMA before. Polydrug use was common
      with half of the sample having concurrently taken another illicit substance--most
      commonly other stimulants (amphetamines and cocaine). A wide range of adverse
      clinical features was found. The most common symptoms were vague and non-specific
      such as feeling strange or unwell, however many patients had collapsed or lost
      consciousness. The most common signs elicited were related to sympathetic
      overactivity, agitation/disturbed behaviour, and increased temperature. The more
      serious complications of delirium, seizures, and profound unconsciousness (coma)
      were commoner when MDMA was used in combination with other substances.
      CONCLUSIONS: For young adults presenting late at night at weekends and exhibiting
      symptoms of sympathetic overactivity, disturbed behaviour, and increased
      temperature ("Saturday night fever") the use of stimulant dance drugs especially
      MDMA should be suspected. As MDMA use does not appear to occur in isolation, the
      clinical picture is likely to be complicated by multiple rather than single drug
      ingestion. This poses increased diagnostic and management challenges for A&E
      staff who typically represent the front line response to dance drug related
      problems.

PMID- 9785162
TI  - Perceived contraindications to thrombolytic treatment in acute myocardial
      infarction. A survey at a teaching hospital.
AB  - OBJECTIVE: To examine the use of thrombolytic treatment in acute myocardial
      infarction when faced with perceived contraindications to treatment and to
      explore the justification for withholding treatment in such clinical situations.
      METHODS: Interview survey of all doctors responsible administering thrombolysis
      to patients with acute myocardial infarction at a teaching hospital in the UK
      from March to May 1997. RESULTS: 20 doctors were interviewed and asked whether
      they would give or withhold thrombolysis in a series of 19 clinical situations.
      These included patients presenting with both an acute myocardial infarction and
      one of the following associated conditions: a confirmed gastrointestinal
      haemorrhage, a suspected gastrointestinal haemorrhage, a peptic ulcer, an
      abdominal aortic aneurysm, a recent cerebrovascular accident, a known
      intracranial aneurysm, a known intracranial tumour, a recent dental extraction,
      recent surgery, severe hypertension, proliferative diabetic retinopathy, a
      history of bleeding diathesis, coma, recent cardiopulmonary resuscitation,
      pregnancy, menstruation, and a recent central venous puncture. In all but one of
      the clinical situations (definite current gastrointestinal haemorrhage) there was
      wide variation in response as to what constitutes a contraindication to
      thrombolytic treatment. Overall, a substantial proportion of doctors (35%-95%)
      would withhold treatment on account of any one of these clinical histories.
      CONCLUSION: Clinicians may be withholding thrombolysis in acute myocardial
      infarction on account of perceived contraindications for which there is little or
      no evidence of increased haemorrhagic risk. An effective treatment for acute
      myocardial infarction is probably being underused.

PMID- 9785161
TI  - Use of an electric ear syringe in the emergency department.
AB  - OBJECTIVES: To introduce an electric ear syringe into an emergency department and
      evaluate its use in the removal of foreign bodies from the external auditory
      canal. METHODS: Report of the use of a new device (the Propulse electric ear
      syringe) in an emergency department with a retrospective audit of the management
      of all cases of aural foreign bodies during one year. RESULTS: Almost 60% of the
      84 patients who presented with foreign bodies in the auditory canal were
      children. Staff chose to treat over half of all patients with aural foreign
      bodies with the electric ear syringe. The overall success rates for the removal
      of the foreign bodies were: electric syringe, 93% in adults and 88% in children
      and instrumentation, 68% in adults and 50% in children. CONCLUSIONS: Irrigation
      with an electric ear syringe is an effective method of removing foreign bodies
      from the external auditory canal. The device tested was safe, inexpensive, easy
      to use, and readily acceptable to both adults and children. The availability of
      an electric ear syringe in an emergency department can avoid the need for
      specialist referral and the subsequent removal of foreign bodies under general
      anaesthesia.

PMID- 9785163
TI  - Life threatening airway obstruction: a hazard of concealed eating disorders.
AB  - The ingestion of unusual objects is not uncommon in florid mental illness. Less
      common is the accidental ingestion of a foreign body which has been used to
      induce vomiting. A case is reported of complete dysphagia that resulted from
      impaction of a plastic fork in the hypopharynx. The patient had been attempting
      to induce vomiting and, as a result of the presentation, was found to be
      suffering from a previously concealed eating disorder (bulimia). Self induced
      vomiting is one criterion for the diagnosis of bulimia and a review of the
      literature indicates that accidental ingestion of large foreign bodies is an
      increasingly familiar hazard of occult bulimia.

PMID- 9785164
TI  - Serotonin syndrome due to venlafaxine overdose.
AB  - A case is presented of serotonin syndrome after deliberate overdose of the
      antidepressant venlafaxine. The mechanism, diagnosis, and management of this
      disorder is discussed.

PMID- 9785165
TI  - Puffer fish poisoning.
AB  - Regarded by many as a delicacy, puffer fish (Lagocephalus scleratus) is a lethal
      source of food poisoning with a high mortality. It contains tetrodotoxin which
      can cause death by muscular paralysis, respiratory depression, and circulatory
      failure. A case of mild intoxication is reported and the literature reviewed.

PMID- 9785166
TI  - Investigation of the head injured patient.

PMID- 9785168
TI  - Audit in the accident and emergency department.

PMID- 9785167
TI  - Later investigation of head injury.

PMID- 9785169
TI  - Continuing medical education one year on--how was it for me?
AB  - Over the period of a year I have systematically recorded any episodes of
      continuing medical education (CME) that I have attended, and reflect on the
      effectiveness of this system in terms of whether it has achieved its objective,
      that is, has my behaviour changed, and whether the existence of the need to
      record CME has influenced this effect. I consider which aspects of CME have been
      most beneficial. I conclude that the proposed level of CME is readily achievable,
      useful, but costly. The way in which I learn most or best is in preparing
      presentations or teaching sessions. There has been some debate on the usefulness
      of keeping a record of CME to which I would like to add my opinion. I also
      recommend the form of record keeping I have used as an impetus to reflection and
      research on the topic of education received, as this reinforces and enhances the
      educational experience.

PMID- 9785170
TI  - Should relatives be allowed in the resuscitation room?

PMID- 9785171
TI  - Should relatives be allowed in the resuscitation room?

PMID- 9785172
TI  - Anterior glenohumeral dislocation.

PMID- 9785173
TI  - Do we need to be propped up with protocols?

PMID- 9785174
TI  - CS "gas" is not a gas.

PMID- 9785175
TI  - Fire.

PMID- 9785176
TI  - Foreign body removal from children's noses.

PMID- 9785177
TI  - Alcohol intoxication.

PMID- 9785178
TI  - VA aligns health professions education with healthcare priorities.
AB  - In 1997, the Veterans Health Administration constituted the Associated Health
      Professions Education Review Committee to provide recommendations for its
      associated health training programs. The Committee recommended that support for
      the 54,000 trainees in over 45 non-physician disciplines that train every year in
      VA facilities be allocated based on patient-focused criteria that emphasize the
      VA's healthcare priorities. Such priorities include accessible primary care,
      geriatrics, treatment of substance abuse, chronic care, and rehabilitation. The
      Committee also placed a high priority on disciplines that demonstrate inter
      professional strategies for healthcare delivery and training. Educational
      institutions and disciplines that address these needs in innovative ways will
      find opportunities for clinical training in VA settings.

PMID- 9785179
TI  - Analysis of practice-role perceptions of physical therapy, occupational therapy,
      and speech-language therapy students.
AB  - The purpose of this study was to determine whether physical therapy (PT),
      occupational therapy (OT), and speech-language therapy (SLP) students shared
      common perceptions of the practice roles of the three disciplines. The survey
      instrument used in this study contained 55 questions that addressed practice-role
      perceptions. The questions were based on a case study. A total of 172
      undergraduate students (PT 71, OT 52, SLP 49) from a southeastern university
      participated. Chi-square test of association was used to analyze the data.
      Results showed that PT, OT, and SLP students shared common perceptions of
      administrative and educational practice roles but differed on their perceptions
      of assessment and physical/mental treatment roles. Practice-role confusion was
      particularly acute between OT and PT and between OT and SLP students in these
      areas.

PMID- 9785180
TI  - Developing and implementing interprofessional learning in a Faculty of Health
      Professions.
AB  - Interprofessional education enables health professional students to learn
      together in order to work together. The Faculty of Health Professions at
      Dalhousie University has developed interprofessional learning within the core
      curriculum of eight educational programs. An interprofessional coordinator
      consulted with students and faculty to prepare a collective statement of the
      purpose, learning models, and implementation principles of interprofessional
      learning. Planning, implementation, and evaluation of a first interprofessional
      module, Professional Ethics: Issues of Autonomy, was carried out by the
      interprofessional Working Group with representation from all programs in the
      faculty. 437 students (25-30 per session) participated in the first three-hour
      interprofessional module, which was offered in 16 evening sessions. Evaluation
      themes included the positive aspect of contact and discussion with students from
      other health professions, and the need to include medical students. The Faculty
      of Health Professions is planning to improve upon this first module, introduce
      other modules, and extend contact with other university faculties and community
      professionals.

PMID- 9785181
TI  - Teaching at a distance using interactive video.
AB  - The University of Kentucky Center for Rural Health has used interactive video
      (IAV) instruction for place-committed students since 1991. Without adequate
      planning and training, new IAV instructors are likely to underestimate the
      differences between IAV and traditional instruction. This paper focuses on
      problems encountered in early stages of IAV implementation. The problems related
      to preparation and delivery of course materials, instructional coordination,
      student-faculty interaction, instructional technique, and equipment. Instructors
      initially emphasized control of IAV technology rather than adopting appropriate
      instructional methods or graphics, and misjudged the time needed to prepare and
      deliver course materials. Team teaching diminished student-faculty interaction,
      and faculty interacted more with local-site than remote-site students.
      Traditional teaching methods were less effective when applied to IAV. Equipment
      failures forced development of contingency plans. Recommendations for the
      avoidance or minimization of such problems are provided. Methods for the
      evaluation of student mastery of course content are briefly described.

PMID- 9785182
TI  - Research productivity and activities of clinical laboratory science faculty: a
      follow-up study.
AB  - A national study was conducted in 1996 to compare clinical laboratory science
      faculty demographics, scholarly activities, and perceptions of the research
      environment with corresponding data reported in 1988. Faculty have made progress
      in earning doctorates (46%), achieving higher ranks (49%), and getting tenured
      (50%). Relatively few faculty are conducting much of the research, with the
      greater majority serving as teachers. Research productivity, as evaluated via
      research publications and presentations, showed that in 1996, full professors and
      those with doctorates published the most articles and abstracts in refereed
      journals; they also made more presentations than junior faculty. Faculty in
      research universities were more productive than those in four-year colleges and
      universities. The faculty surveyed in 1985 and those surveyed in 1996 perceived
      their research skills and environments to be almost identical. In both 1985 and
      1996, the importance of research for promotion and tenure decisions ranked
      highest as a characteristic of the environment. Financial resources and time
      available for research ranked lowest.

PMID- 9785183
TI  - Enhancement of achievement and attitudes through individualized learning-style
      presentations of two allied health courses.
AB  - This investigation analyzed the effects of the instructional resource Programmed
      Learning Sequence (PLS) on the achievement and attitudes of college students and
      correlated the findings with the individuals' learning styles. The subjects were
      enrolled in Sonography I and Cross-Sectional Anatomy in a college of health
      related professions. Both classes were administered the Productivity
      Environmental Preference Survey to identify learning-style strengths, and
      alternately presented with lessons using a PLS in a book format and traditional
      lectures. The sonography class also was exposed to a PLS in multimedia computer
      format. The Semantic Differential Scale measured the students' attitudes
      comparing the instructional methods experienced, and class examinations measured
      content mastery. In both classes, examination scores were significantly higher
      (effect size for the sonography class was 1.42; for the anatomy class, 0.63) and
      students' attitude scores were significantly higher when PLS rather than the
      traditional method was used. In the sonography class, achievement was
      significantly higher with the book PLS than with the computer PLS (effect size,
      1.11). Significant correlations emerged between learning-style elements and
      achievement: students who preferred learning with the book PLS required more
      quiet in the environment than did those who preferred the computer PLS; students
      who preferred learning traditionally and with the computer PLS required more
      light than those preferring the book PLS; and students who preferred learning
      with an authority figure favored the traditional method. Examination of the data
      for other correlations between learning-style preferences and attitudes using the
      book PLS also revealed many other significant findings, demonstrating its ability
      to accommodate diverse styles.

PMID- 9785184
TI  - Strategies to expand the definition of scholarship for the health professions.
AB  - Standards for promotions and tenure for health professions faculty must require
      the same intellectual and methodologic rigor as those in other academic areas.
      The challenge is to expand the traditional view of scholarship as research to
      include scholarship of teaching, application, and integration and to develop
      methods for documenting these. This article describes four strategies instituted
      by Allegheny University of the Health Sciences to address this challenge. Results
      of two of the strategies, a workshop for appointments and promotions and tenure
      committee members, and a workshop for preparing junior faculty for academic
      advancement are discussed. The four strategies described are intended to serve as
      models to stimulate discussion and innovation at other institutions.

PMID- 9785185
TI  - Evaluating the marginal student: a workshop for clinical faculty.
AB  - This article outlines a workshop designed to assist faculty in identifying
      students who are marginal or borderline and difficult to evaluate. The workshop's
      curriculum was tested out in three separate contexts over a 15-month period. The
      article also presents the results of the evaluation of the workshop curriculum
      and illustrates the complexities of relevant issues by using case scenarios that
      reflect the concerns shared among an interdisciplinary health sciences faculty.
      Responses to a post-workshop questionnaire indicated that the participants had
      benefitted from it and recommended its continuance.

PMID- 9785186
TI  - Information technology education for health professionals: opportunities and
      challenges.
AB  - Computer applications are on the increase in virtually every aspect of health
      care, from the routine management of information to clinical diagnoses or
      clinical decision making. Indeed, the use of computers extends from patient
      monitoring and point-of-care testing to basic and applied research. Given the
      ubiquity of computers in health care, it is crucial that health professions
      education programs provide students with the computer proficiencies they need to
      apply to their roles as health professionals. This article highlights the
      importance of such training. It also provides results of two separate needs
      assessment surveys, and presents curriculum design strategies and competencies to
      meet health care's present and emerging information technology needs.

PMID- 9785187
TI  - Building community: developing skills for interprofessional health professions
      education and relationship-centered care. NLN Appointed Interdisciplinary Health
      Education Panel.

PMID- 9785188
TI  - The perennial federal budget struggle.

PMID- 9785190
TI  - Human embryo viability: what determines developmental potential, and can it be
      assessed?
AB  - The understanding of the embryo's nutrient requirements and physiology has led to
      the development of more physiological culture media, capable of supporting
      acceptable levels of human blastocyst development in vitro. The success of such
      media can be attributed to catering to the embryo's changing nutrient
      requirements, while minimizing culture-induced stress, thereby facilitating
      normal cell function. Most important, blastocysts derived from such sequential
      culture systems have a high viability. The ability to identify those blastocysts
      from within a given cohort which have the highest developmental potential will
      lead to further increases in implantation and pregnancy rate. Such an approach
      should ultimately lead to the routine transfer of a single blastocyst in a given
      IVF cycle, while being able to maintain a high pregnancy rate.

PMID- 9785191
TI  - Mammalian embryo quality: is it possible to estimate it, and when?

PMID- 9785192
TI  - Role of autocrine mediators in the regulation of embryo viability: lessons from
      animal models.